PMID- 29044165
TI  - In Vivo Neuromechanics: Decoding Causal Motor Neuron Behavior with Resulting
      Musculoskeletal Function.
AB  - Human motor function emerges from the interaction between the neuromuscular and
      the musculoskeletal systems. Despite the knowledge of the mechanisms underlying
      neural and mechanical functions, there is no relevant understanding of the neuro
      mechanical interplay in the neuro-musculo-skeletal system. This currently
      represents the major challenge to the understanding of human movement. We address
      this challenge by proposing a paradigm for investigating spinal motor neuron
      contribution to skeletal joint mechanical function in the intact human in vivo.
      We employ multi-muscle spatial sampling and deconvolution of high-density fiber
      electrical activity to decode accurate alpha-motor neuron discharges across five
      lumbosacral segments in the human spinal cord. We use complete alpha-motor neuron
      discharge series to drive forward subject-specific models of the musculoskeletal
      system in open-loop with no corrective feedback. We perform validation tests
      where mechanical moments are estimated with no knowledge of reference data over
      unseen conditions. This enables accurate blinded estimation of ankle function
      purely from motor neuron information. Remarkably, this enables observing causal
      associations between spinal motor neuron activity and joint moment control. We
      provide a new class of neural data-driven musculoskeletal modeling formulations
      for bridging between movement neural and mechanical levels in vivo with
      implications for understanding motor physiology, pathology, and recovery.

PMID- 29044166
TI  - Minimal methylation classifier (MIMIC): A novel method for derivation and rapid
      diagnostic detection of disease-associated DNA methylation signatures.
AB  - Rapid and reliable detection of disease-associated DNA methylation patterns has
      major potential to advance molecular diagnostics and underpin research
      investigations. We describe the development and validation of minimal methylation
      classifier (MIMIC), combining CpG signature design from genome-wide datasets,
      multiplex-PCR and detection by single-base extension and MALDI-TOF mass
      spectrometry, in a novel method to assess multi-locus DNA methylation profiles
      within routine clinically-applicable assays. We illustrate the application of
      MIMIC to successfully identify the methylation-dependent diagnostic molecular
      subgroups of medulloblastoma (the most common malignant childhood brain tumour),
      using scant/low-quality samples remaining from the most recently completed pan
      European medulloblastoma clinical trial, refractory to analysis by conventional
      genome-wide DNA methylation analysis. Using this approach, we identify critical
      DNA methylation patterns from previously inaccessible cohorts, and reveal novel
      survival differences between the medulloblastoma disease subgroups with
      significant potential for clinical exploitation.

PMID- 29044167
TI  - Impact of heavy metal lead stress on polyamine levels in Halomonas BVR 1 isolated
      from an industry effluent.
AB  - In living systems, environmental stress due to biotic and abiotic factors
      triggers the production of myriad metabolites as a potential mechanism for
      combating stress. Among these metabolites are the small polycationic aliphatic
      amine molecules - polyamines, which are ubiquitous in all living organisms. In
      this work, we demonstrate a correlation between cellular concentration of three
      major polyamines (putrescine, spermidine and spermine) with lead exposure on
      bacteria for a period of 6-24 h. We report that indigenously isolated Halomonas
      sp. strain BVR 1 exhibits lead induced fluctuations in their cellular polyamine
      concentration. This response to lead occurs within 6 h post metal treatment.
      During the same time interval there was a surge in the growth of bacteria along
      with an enhancement in the putrescine levels. We conclude that in Halomonas sp.
      strain BVR 1, an early response is seen with respect to modulation of polyamines
      as a result of lead treatment and hypothesize that endogenous polyamines
      contribute towards scavenging lead in these bacteria.

PMID- 29044168
TI  - SQUID-based detection of ultra-low-field multinuclear NMR of substances
      hyperpolarized using signal amplification by reversible exchange.
AB  - Ultra-low-field (ULF) nuclear magnetic resonance (NMR) is a promising
      spectroscopy method allowing for, e.g., the simultaneous detection of multiple
      nuclei. To overcome the low signal-to-noise ratio that usually hampers a wider
      application, we present here an alternative approach to ULF NMR, which makes use
      of the hyperpolarizing technique signal amplification by reversible exchange
      (SABRE). In contrast to standard parahydrogen hyperpolarization, SABRE can
      continuously hyperpolarize 1 H as well as other MR-active nuclei. For
      simultaneous measurements of 1 H and 19 F under SABRE conditions a
      superconducting quantum interference device (SQUID)-based NMR detection unit was
      adapted. We successfully hyperpolarized fluorinated pyridine derivatives with an
      up to 2000-fold signal enhancement in 19 F. The detected signals may be explained
      by two alternative reaction mechanisms. SABRE combined with simultaneous SQUID
      based broadband multinuclear detection may enable the quantitative analysis of
      multinuclear processes.

PMID- 29044169
TI  - Effect of laser surface remelting on the microstructure and properties of Al
      Al2Cu-Si ternary eutectic alloy.
AB  - Bimodal ultrafine eutectic composites (BUECs) exhibit a good combination of
      strength and plasticity owing to a dual-hierarchy in eutectic length-scales in
      the microstructure. The present study investigates the variation of phase,
      morphology, feature length-scales and modality of microstructures obtained in a
      Al81Cu13Si6 (at. %) ternary alloy after laser surface remelting. A novel approach
      of varying component bimodal eutectic volume fractions by controlling the cooling
      rate of the laser solidification process has been presented. The volume fraction
      of the fine eutectic matrix has a profound effect on the flow strength. Laser
      remelted microstructures with volume fractions of the fine eutectic varying from
      25 to 40% exhibiting compressive flow strengths ranging from 500 to 900 MPa have
      been obtained. The volume fraction of the fine eutectic decreased with cooling
      rate and completely ceased to exist at cooling rates greater than [Formula: see
      text].

PMID- 29044170
TI  - Phosphorylation regulates the subcellular localization of Cucumber Mosaic Virus
      2b protein.
AB  - The 2b protein of Cucumber mosaic virus has a role in nearly all steps of the
      viral cycle including cell-to-cell movement, symptom induction and suppression of
      antiviral RNA silencing. Previous studies demonstrated the presence of 2b protein
      in the nucleus and in cytoplasm as well. Phosphorylation site of 2b protein is
      conserved in all CMV isolates, including proposed constitute motifs for casein
      kinase II and cyclin-dependent kinase 2. To discern the impact of 2b protein
      phosphorylation, we created eight different mutants to mimic the non
      phosporylated (serine to alanine) as well as the phosphorylated state (serine to
      aspartic acid) of the protein. We compared these mutants to the wild-type (Rs
      CMV) virus in terms of symptom induction, gene silencing suppressor activity as
      well as in cellular localization. Here, in this study we confirmed the
      phosphorylation of 2b protein in vivo, both in infected N. benthamiana and in
      infiltrated patches. Mutants containing aspartic acid in the phosphorylation site
      accumulated only in the cytoplasm indicating that phosphorylated 2b protein could
      not enter the nucleus. We identified a conserved dual phosphorylation switch in
      CMV 2b protein, which equilibrates the shuttling of the 2b protein between the
      nucleus and the cytoplasm, and regulates the suppressor activity of the 2b
      protein.

PMID- 29044171
TI  - Pharmacological sensitivity of reflexive and nonreflexive outcomes as a correlate
      of the sensory and affective responses to visceral pain in mice.
AB  - Pain encompasses both sensory and affective dimensions which can be
      differentially modulated by drugs. Here, we compare the pharmacological
      sensitivity of the sensory and affective responses using acetic acid-induced
      abdominal writhings (sensory-reflexive outcome) and acetic acid-induced
      depression of reward seeking behaviour (RSB, affective-nonreflexive outcome) to a
      highly palatable food in mice. We found that the expression of RSB critically
      depends on factors such as sex and previous knowledge and type of the food
      stimulus. Intraperitoneal administration of acetic acid (iAA) produced a long
      lasting (beyond the resolution of writhing behaviour) and concentration-dependent
      decrease on both appetitive-approach and consummatory dimensions of RSB.
      Ibuprofen and diclofenac were much more potent in reversing AA-induced changes in
      RSB: latency to eat (ED50 = 2 and 0.005 mg/kg, intraperinoneally, respectively)
      and amount consumed (ED50 = 11 and 0.1 mg/kg) than in AA-induced writhing (ED50 =
      123 and 60 mg/kg). Morphine and duloxetine inhibited the writhing response (ED50
      = 0.8 and 6 mg/kg, respectively) but not the AA-induced changes in RSB. Caffeine
      was ineffective in both AA-induced writhing and RSB changes. Overall, this study
      characterized a preclinical mouse model of hedonic deficits induced by pain that
      can be used to assess affective responses as well as complementary classic
      reflexive approaches in the evaluation of candidate analgesics.

PMID- 29044172
TI  - Circulating miR-19b and miR-181b are potential biomarkers for diabetic
      cardiomyopathy.
AB  - Diabetic cardiomyopathy is characterized by metabolic changes in the myocardium
      that promote a slow and silent dysfunction of muscle fibers, leading to
      myocardium remodelling and heart failure, independently of the presence of
      coronary artery diseases or hypertension. At present, no imaging methods allow an
      early diagnosis of this disease. Circulating miRNAs in plasma have been proposed
      as biomarkers in the prognosis of several cardiac diseases. This study aimed to
      determine whether circulating miRNAs could be potential biomarkers of diabetic
      cardiomyopathy. Mice that were fed with a high fat diet for 16 months, showed
      metabolic syndrome manifestations, cardiac hypertrophy (without hypertension) and
      a progressive cardiac function decline. At 16 months, when maximal degree of
      cardiac dysfunction was observed, 15 miRNAs from a miRNA microarray screening in
      myocardium were selected. Then, selected miRNAs expression in myocardium (at 4
      and 16 months) and plasma (at 4, 12 and 16 months) were measured by RT-qPCR.
      Circulating miR-19b-3p and miR-181b-5p levels were associated with myocardium
      levels during the development of diabetic cardiomyopathy (in terms of cardiac
      dysfunction), suggesting that these miRNAs could be suitable biomarkers of this
      disease in asymptomatic diabetic patients.

PMID- 29044173
TI  - Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal
      beta cells and human pancreatic islets.
AB  - Type 2 diabetes is characterized by progressive beta cell dysfunction, with
      lipotoxicity playing a possible pathogenetic role. Palmitate is often used to
      examine the direct effects of lipotoxicity and it may cause mitochondrial
      alterations by activating protein acetylation. However, it is unknown whether
      palmitate influences protein acetylation in beta cells. We investigated lysine
      acetylation in mitochondrial proteins from INS-1E beta cells (INS-1E) and in
      proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First,
      we confirmed that palmitate damages beta cells and demonstrated that chemical
      inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2
      D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry
      we evaluated the effects of palmitate on protein acetylation. In mitochondrial
      preparations from palmitate-treated INS-1E, 32 acetylated spots were detected,
      with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were
      found, of which 11 were over-acetylated upon culture with palmitate.
      Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide
      dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore,
      prolonged exposure to palmitate induces changes in beta cell protein lysine
      acetylation and this modification could play a role in causing beta cell damage.
      Dysregulated acetylation may be a target to counteract palmitate-induced beta
      cell lipotoxicity.

PMID- 29044174
TI  - Phase-driven charge manipulation in Hybrid Single-Electron Transistor.
AB  - Phase-tunable hybrid devices, built upon nanostructures combining normal metal
      and superconductors, have been the subject of intense studies due to their
      numerous combinations of different charge and heat transport configurations. They
      exhibit solid applications in quantum metrology and coherent caloritronics. Here
      we propose and realize a new kind of hybrid device with potential application in
      single charge manipulation and quantized current generation. We show that by
      tuning superconductivity on two proximized nanowires, coupled via a Coulombic
      normal-metal island, we are able to control its charge state configuration. This
      device supports a one-control-parameter cycle being actuated by the sole magnetic
      flux. In a voltage biased regime, the phase-tunable superconducting gaps can act
      as energy barriers for charge quanta leading to an additional degree of freedom
      in single electronics. The resulting configuration is fully electrostatic and the
      current across the device is governed by the quasiparticle populations in the
      source and drain leads. Notably, the proposed device can be realized using
      standard nanotechniques opening the possibility to a straightforward coupling
      with the nowadays well developed superconducting electronics.

PMID- 29044175
TI  - A Skeletal Muscle Model of Infantile-onset Pompe Disease with Patient-specific
      iPS Cells.
AB  - Pompe disease is caused by an inborn defect of lysosomal acid alpha-glucosidase
      (GAA) and is characterized by lysosomal glycogen accumulation primarily in the
      skeletal muscle and heart. Patients with the severe type of the disease,
      infantile-onset Pompe disease (IOPD), show generalized muscle weakness and heart
      failure in early infancy. They cannot survive over two years. Enzyme replacement
      therapy with recombinant human GAA (rhGAA) improves the survival rate, but its
      effect on skeletal muscle is insufficient compared to other organs. Moreover, the
      patho-mechanism of skeletal muscle damage in IOPD is still unclear. Here we
      generated induced pluripotent stem cells (iPSCs) from patients with IOPD and
      differentiated them into myocytes. Differentiated myocytes showed lysosomal
      glycogen accumulation, which was dose-dependently rescued by rhGAA. We further
      demonstrated that mammalian/mechanistic target of rapamycin complex 1 (mTORC1)
      activity was impaired in IOPD iPSC-derived myocytes. Comprehensive metabolomic
      and transcriptomic analyses suggested the disturbance of mTORC1-related
      signaling, including deteriorated energy status and suppressed mitochondrial
      oxidative function. In summary, we successfully established an in vitro skeletal
      muscle model of IOPD using patient-specific iPSCs. Disturbed mTORC1 signaling may
      contribute to the pathogenesis of skeletal muscle damage in IOPD, and may be a
      potential therapeutic target for Pompe disease.

PMID- 29044176
TI  - Proteomic Analysis Reveals Dab2 Mediated Receptor Endocytosis Promotes Liver
      Sinusoidal Endothelial Cell Dedifferentiation.
AB  - Sinusoidal dedifferentiation is a complicated process induced by several factors,
      and exists in early stage of diverse liver diseases. The mechanism of sinusoidal
      dedifferentiation is poorly unknown. In this study, we established a NaAsO2
      induced sinusoidal dedifferentiation mice model. Liver sinusoidal endothelial
      cells were isolated and isobaric tag for relative and absolute quantitation
      (iTRAQ) based proteomic approach was adopted to globally examine the effects of
      arsenic on liver sinusoidal endothelial cells (LSECs) during the progression of
      sinusoidal dedifferentiation. In all, 4205 proteins were identified and
      quantified by iTRAQ combined with LC-MS/MS analysis, of which 310 proteins were
      significantly changed in NaAsO2 group, compared with the normal control.
      Validation by western blot showed increased level of clathrin-associated sorting
      protein Disabled 2 (Dab2) in NaAsO2 group, indicating that it may regulate
      receptor endocytosis, which served as a mechanism to augment intracellular VEGF
      signaling. Moreover, we found that knockdown of Dab2 reduced the uptake of VEGF
      in LSECs, furthermore blocking VEGF-mediated LSEC dedifferentiation and
      angiogenesis.

PMID- 29044177
TI  - Strong associations between chromosomal aberrations in blood lymphocytes and the
      risk of urothelial and squamous cell carcinoma of the bladder.
AB  - : Chromosomal aberrations (CAs) in blood lymphocytes have been shown to be
      associated with overall cancer risk and aging. However, their relationship to
      bladder cancer risk remains to be elucidated. In a case-control study of bladder
      cancer in Egypt, we examined the relationship between the increased frequency of
      CAs in blood lymphocytes and bladder cancer risk. High frequency of CAs was
      significantly associated with an increased risk of bladder cancer [adjusted odds
      ratios (OR) = 3.90, 95% confidence interval (CI) = 2.65-5.73]. The associations
      were somewhat stronger in squamous cell carcinomas (SCC, OR = 4.90) than in
      urothelial carcinomas (UC, OR = 3.62). We also identified chromosome specific CAs
      for chromosomes 3, 4, 5, 8, 9, 10, 11, 12, 17, 19 that were significantly
      associated with an increased risk of bladder cancer. We observed particularly
      strong associations between aberrations of chromosomes 12, 13, 17 and risk of SCC
      (OR = 7.06, 6.91 and 6.23, respectively). CONCLUSION: increased frequency of
      chromosomal aberrations in blood lymphocytes was significantly associated with
      bladder cancer risk. Overall and chromosome specific aberrations in blood
      lymphocytes may be a unique set of biomarkers for risk assessments of SCC and UC.

PMID- 29044178
TI  - Use of PIXE/PIGE for sequential Ca and F measurements in root carious model.
AB  - The progress of caries has conventionally been evaluated by checking changes in
      mineral density using transverse microradiography (TMR). Recent advances have
      seen development of a new measurement system, using in-air micro proton induced X
      ray/gamma-ray emission (PIXE/PIGE). PIXE/PIGE enables analysis of distributions
      and concentrations of multiple mineral elements in a carious lesion. The aim of
      this study was to evaluate the effectiveness of PIXE/PIGE for investigating the
      development of root caries. In summary, we successfully established a multi
      elemental sequential measuring method using in-air micro-PIXE/PIGE to identify
      the dynamic distributions and concentrations of Ca and F in human root dentin.
      The PIXE/PIGE potentially offers a useful advantageous technique for studying
      carious development by using as a combination with conventional techniques such
      as TMR and Micro-computed tomography (uCT).

PMID- 29044179
TI  - The effect of insecticide synergist treatment on genome-wide gene expression in a
      polyphagous pest.
AB  - Synergists can counteract metabolic insecticide resistance by inhibiting
      detoxification enzymes or transporters. They are used in commercial formulations
      of insecticides, but are also frequently used in the elucidation of resistance
      mechanisms. However, the effect of synergists on genome-wide transcription in
      arthropods is poorly understood. In this study we used Illumina RNA-sequencing to
      investigate genome-wide transcriptional responses in an acaricide resistant
      strain of the spider mite Tetranychus urticae upon exposure to synergists such as
      S,S,S-tributyl phosphorotrithioate (DEF), diethyl maleate (DEM), piperonyl
      butoxide (PBO) and cyclosporin A (CsA). Exposure to PBO and DEF resulted in a
      broad transcriptional response and about one third of the differentially
      expressed genes (DEGs), including cytochrome P450 monooxygenases and UDP
      glycosyltransferases, was shared between both treatments, suggesting common
      transcriptional regulation. Moreover, both DEF and PBO induced genes that are
      strongly implicated in acaricide resistance in the respective strain. In
      contrast, CsA treatment mainly resulted in downregulation of Major Facilitator
      Superfamily (MFS) genes, while DEGs of the DEM treatment were not significantly
      enriched for any GO-terms.

PMID- 29044180
TI  - Evaluating phenotype-driven approaches for genetic diagnoses from exomes in a
      clinical setting.
AB  - Next generation sequencing is transforming clinical medicine and genome research,
      providing a powerful route to establishing molecular diagnoses for genetic
      conditions; however, challenges remain given the volume and complexity of genetic
      variation. A number of methods integrate patient phenotype and genotypic data to
      prioritise variants as potentially causal. Some methods have a clinical focus
      while others are more research-oriented. With clinical applications in mind we
      compare results from alternative methods using 21 exomes for which the disease
      causal variant has been previously established through traditional clinical
      evaluation. In this case series we find that the PhenIX program is the most
      effective, ranking the true causal variant at between 1 and 10 in 85% of these
      cases. This is a significantly higher proportion than the combined results from
      five alternative methods tested (p = 0.003). The next best method is Exomiser
      (hiPHIVE), in which the causal variant is ranked 1-10 in 25% of cases. The widely
      different targets of these methods (more clinical focus, considering known
      Mendelian genes, in PhenIX, versus gene discovery in Exomiser) is perhaps not
      fully appreciated but may impact strongly on their utility for molecular
      diagnosis using clinical exome data.

PMID- 29044181
TI  - A Novel beta-adaptin/c-Myc Complex Formation Modulated by Oxidative Stress in the
      Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis.
AB  - Our study tested the proposal that c-Myc activation in macrophages is
      differentially carried out dependent on the intracellular oxidative state of
      cells and potentially associated to the process of atherogenesis. Under our
      experimental conditions, the generation of reactive oxygen species carried out by
      the presence of oxidized low density lipoproteins (oxLDL) or Gram negative
      bacterial lipopolysaccharides (LPS) modifies the expression of cellular adhesion
      molecules such as c-Abl, calcium transport proteins such as the plasma membrane
      Ca2+-ATPase (PMCA), CD47, procaspase-7, CASP7, CHOP, transcriptional activators
      such as c-Jun and c-Myc and molecules that participate in the process of
      endocytosis like alpha- and beta-adaptin. We present the first evidence showing
      that a state of oxidative stress alters c-Myc-dependent activity pathways in
      macrophages through binding to molecules such as beta-adaptin promoting the
      reversible formation of a complex that presents the ability to regulate the
      development of the cell cycle. We propose that the subtle regulation carried out
      through the formation of this c-Myc/beta-adaptin complex when cells change from a
      normal physiological condition to a state of oxidative stress, represents a
      defense mechanism against the deleterious effects caused by the loss of cell
      homeostasis.

PMID- 29044183
TI  - Direct Production of Furfural in One-pot Fashion from Raw Biomass Using Bronsted
      Acidic Ionic Liquids.
AB  - The conversion of raw biomass into C5-sugars and furfural was demonstrated with
      the one-pot method using Bronsted acidic ionic liquids (BAILs) without any
      mineral acids or metal halides. Various BAILs were synthesized and characterized
      using NMR, FT-IR, TGA, and CHNS microanalysis and were used as the catalyst for
      raw biomass conversion. The remarkably high yield (i.e. 88%) of C5 sugars from
      bagasse can be obtained using 1-methyl-3(3-sulfopropyl)-imidazolium hydrogen
      sulfate ([C3SO3HMIM][HSO4]) BAIL catalyst in a water medium. Similarly, the
      [C3SO3HMIM][HSO4] BAIL also converts the bagasse into furfural with very high
      yield (73%) in one-pot method using a water/toluene biphasic solvent system.

PMID- 29044182
TI  - Long-term Intake of Pasta Containing Barley (1-3)Beta-D-Glucan Increases
      Neovascularization-mediated Cardioprotection through Endothelial Upregulation of
      Vascular Endothelial Growth Factor and Parkin.
AB  - Barley (1-3)beta-D-Glucan (BBG) enhances angiogenesis. Since pasta is very
      effective in providing a BBG-enriched diet, we hypothesized that the intake of
      pasta containing 3% BBG (P-BBG) induces neovascularization-mediated
      cardioprotection. Healthy adult male C57BL/6 mice fed P-BBG (n = 15) or wheat
      pasta (Control, n = 15) for five-weeks showed normal glucose tolerance and
      cardiac function. With a food intake similar to the Control, P-BBG mice showed a
      109% survival rate (P < 0.01 vs. Control) after cardiac ischemia (30
      min)/reperfusion (60 min) injury. Left ventricular (LV) anion superoxide
      production and infarct size in P-BBG mice were reduced by 62 and 35% (P < 0.0001
      vs. Control), respectively. The capillary and arteriolar density of P-BBG hearts
      were respectively increased by 12 and 18% (P < 0.05 vs. Control). Compared to the
      Control group, the VEGF expression in P-BBG hearts was increased by 87.7% (P <
      0.05); while, the p53 and Parkin expression was significantly increased by 125%
      and cleaved caspase-3 levels were reduced by 33% in P-BBG mice. In vitro, BBG was
      required to induce VEGF, p53 and Parkin expression in human umbelical vascular
      endothelial cells. Moreover, the BBG-induced Parkin expression was not affected
      by pifithrin-alpha (10 uM/7days), a p53 inhibitor. In conclusion, long-term
      dietary supplementation with P-BBG confers post-ischemic cardioprotection through
      endothelial upregulation of VEGF and Parkin.

PMID- 29044184
TI  - Zebrafish aversive taste co-receptor is expressed in both chemo- and
      mechanosensory cells and plays a role in lateral line development.
AB  - Fishes rely on both chemical and tactile senses to orient themselves to avoid
      predators, and to detect and taste food. This is likely achieved by highly
      coordinated reception of signals by mechano- and chemosensory receptors in fish.
      A small co-receptor from zebrafish, receptor activity modifying protein (RAMP)
      like triterpene glycoside receptor (RL-TGR), was previously found to be involved
      in recognition of triterpene glycosides, a family of naturally occurring
      compounds that act as chemical defenses in various prey species. However, its
      localization, function, and how it impacts sensory organ development in vivo is
      not known. Here we show that RL-TGR is expressed in zebrafish in both i) apical
      microvilli of the chemosensory cells of taste buds including the epithelium of
      lips and olfactory epithelium, and ii) mechanosensory cells of neuromasts
      belonging to the lateral line system. Loss-of-function analyses of RL-TGR
      resulted in significantly decreased number of neuromasts in the posterior lateral
      line system and decreased body length, suggesting that RL-TGR is involved in
      deposition and migration of the neuromasts. Collectively, these results provide
      the first in vivo genetic evidence of sensory cell-specific expression of this
      unusual co-receptor and reveal its additional role in the lateral line
      development in zebrafish.

PMID- 29044185
TI  - Structural analysis of variant of Helicobacter pylori MotB in its activated form,
      engineered as chimera of MotB and leucine zipper.
AB  - Rotation of the bacterial flagellum is powered by a proton influx through the
      peptidoglycan (PG)-tethered stator ring MotA/B. MotA and MotB form an inner
      membrane complex that does not conduct protons and does not bind to PG until it
      is inserted into the flagellar motor. The opening of the proton channel involves
      association of the plug helices in the periplasmic region of the MotB dimer into
      a parallel coiled coil. Here, we have characterised the structure of a soluble
      variant of full-length Helicobacter pylori MotB in which the plug helix was
      engineered to be locked in a parallel coiled coil state, mimicking the open state
      of the stator. Fluorescence resonance energy transfer measurements, combined with
      PG-binding assays and fitting of the crystal structures of MotB fragments to the
      small angle X-ray scattering (SAXS) data revealed that the protein's C-terminal
      domain has a PG-binding-competent conformation. Molecular modelling against the
      SAXS data suggested that the linker in H. pylori MotB forms a subdomain between
      the plug and the C-terminal domain, that 'clamps' the coiled coil of the plug,
      thus stabilising the activated form of the protein. Based on these results, we
      present a pseudo-atomic model structure of full-length MotB in its activated
      form.

PMID- 29044186
TI  - An endophytic microbe from an unusual volcanic swamp corn seeks and inhabits root
      hair cells to extract rock phosphate.
AB  - In the animal microbiome, localization of microbes to specific cell types is well
      established, but there are few such examples within the plant microbiome which
      includes endophytes. Endophytes are non-pathogenic microbes that inhabit plants.
      Root hairs are single cells, equivalent to the nutrient-absorbing intestinal
      microvilli of animals, used by plants to increase the root surface area for
      nutrient extraction from soil including phosphorus (P). There has been
      significant interest in the microbiome of intestinal microvilli but less is known
      about the root hair microbiome. Here we describe a bacterial endophyte (3F11)
      from Zea nicaraguensis, a wild corn discovered in a Nicaraguan swamp above rock-P
      lava flowing from the San Cristobal volcano. Rock-P is insoluble and a major
      challenge for plants. Following seed coating and germination on insoluble-P, the
      endophyte colonized epidermal surfaces, ultimately colonizing root hairs
      intracellularly. The endophyte promoted root hair growth and secreted acids to
      solubilize rock-P for uptake by a larger root hair surface. The most interesting
      observation was that a seed-coated endophyte targeted and colonized a critical
      cell type, root hair cells, consistent with earlier studies. The endophyte
      maintained its targeting ability in two evolutionary divergent hosts, suggesting
      that the host recognition machinery is conserved.

PMID- 29044187
TI  - Tuneable dielectric and optical characteristics of tailor-made inorganic electro
      chromic materials.
AB  - Electro-chromic materials (EC) are a new class of electronically reconfigurable
      thin films that have the ability to reversibly change optical properties by
      electric charge insertion/extraction. Since their discovery by Deb, they have
      been employed in applications related to display technology, such as smart
      windows and mirrors and active optical filters. In this sense, a variety of
      studies related to the tuneable optical characteristics of EC materials have
      recently been reported, however, their microwave tuneable dielectric
      characteristics have been left somewhat unexplored. In 2016 Bulja showed that dc
      bias voltage induced modulation of the optical characteristics of an inorganic
      Conductor/WO3/LiNbO3/NiO/Conductor EC cell isaccompanied by the modulation of its
      high frequency (1-20 GHz) dielectric characteristics. In general, according to
      the state of the art, cells of different material compositions are needed to
      produce devices of tailor made characteristics. Here, we report the discovery
      that the microwave dielectric and the optical characteristics of an EC cell can
      be engineered to suit a variety of applications without changing their material
      composition. The obtained results indicate the potential for producing novel,
      tuneable and tailor-engineered materials that can be used to create next
      generation agile microwave-optical devices.

PMID- 29044188
TI  - The histone variant H3.3 G34W substitution in giant cell tumor of the bone link
      chromatin and RNA processing.
AB  - While transcription as regulated by histones and their post-translational
      modifications has been well described, the function of histone variants in this
      process remains poorly characterized. Potentially important insight into this
      process pertain to the frequently occurring mutations of H3.3, leading to G34
      substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB).
      In this study, we have established primary cell lines from GCTB patients and used
      them to uncover the influence of H3.3 G34W substitutions on cellular growth
      behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3
      G34W showed increased colony formation, infiltration and proliferation, known
      hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated
      the increased proliferation observed in primary cells. Transcriptomic analysis of
      primary cells and tumor biopsies revealed slightly more downregulated gene
      expression, perhaps by increased chromatin compaction. We identified components
      related to splicing, most prominently hnRNPs, by immunoprecipitation and mass
      spectrometry that specifically interact with H3.3 G34W in the isogenic cell
      lines. RNA-sequencing analysis and hybridization-based validations further
      enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing
      and chromatin modulation that is blocked by the G34W substitution, potentially
      driving the tumorigenic process in GCTB.

PMID- 29044189
TI  - TGF-beta signalling and PEG10 are mutually exclusive and inhibitory in
      chondrosarcoma cells.
AB  - Histological distinction between enchondroma and chondrosarcoma is difficult
      because of a lack of definitive biomarkers. Here, we found highly active
      transforming growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP)
      signalling in human chondrosarcomas compared with enchondromas by
      immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the
      chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1
      chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray
      analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819.T cells
      compared with C28/I2 normal chondrocytes, while TGF-beta1 treatment, mimicking
      higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples
      exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting
      a negative association of PEG10 with malignant cartilage tumours. In
      chondrosarcoma cell lines, application of the TGF-beta signalling inhibitor,
      SB431542, increased the protein level of PEG10. Reporter assays revealed that
      PEG10 repressed TGF-beta and BMP signalling, which are both SMAD pathways,
      whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and
      SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and
      phosphorylated SMADs in combination with differentially expressed SOX9 is an
      index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF
      beta signalling are mutually inhibitory in chondrosarcoma cells.

PMID- 29044190
TI  - A high-speed single sideband generator using a magnetic tunnel junction spin
      torque nano-oscillator.
AB  - An important property of spin-torque nano-oscillators (STNOs) is their ability to
      produce a frequency modulated (FM) signal, which is very critical for
      communication applications. We here demonstrate a novel single sideband (SSB)
      modulation phenomenon using a magnetic tunnel junction (MTJ)-based STNO, which
      saves transmission bandwidth and in principle should minimize attenuation for
      wireless communication. Experimentally, lower single sidebands (LSSBs) have been
      successfully demonstrated over a wide range of modulation frequency, f m  = 150
      MHz-1 GHz. The observed LSSBs are determined by the intrinsic properties of the
      device, which can be modeled well by a nonlinear frequency and amplitude
      modulation formulation and reproduced in macrospin simulations. Moreover, our
      macrospin simulation results show that the range of modulation current and
      modulation frequency for generating SSBs can be controlled by the field-like
      torque and biasing conditions.

PMID- 29044191
TI  - LRRC25 Functions as an Inhibitor of NF-kappaB Signaling Pathway by Promoting
      p65/RelA for Autophagic Degradation.
AB  - Nuclear factor kappaB (NF-kappaB) is a family of critical transcription factors
      that play a critical role in innate immune responses and inflammation, yet the
      molecular mechanisms responsible for its tight regulation is not fully
      understood. In this study, we identified LRRC25, a member of leucine-rich repeat
      (LRR)-containing protein family, as a negative regulator in the NF-kappaB
      signaling pathway. Ectopic expression of LRRC25 impaired NF-kappaB activation,
      whereas knockout of LRRC25 potentiated NF-kappaB activation and enhanced the
      production of inflammatory cytokines. Further study demonstrated that the LRR
      domain of LRRC25 interacted with the Rel Homology domain (RHD) of p65/RelA and
      promotes the degradation of p65/RelA. Furthermore, LRRC25 enhanced the
      interaction between p65/RelA and cargo receptor p62, thus facilitating the
      degradation of p65/RelA through autophagy pathway. Our study has not only
      identified LRRC25 as a novel inhibitor of NF-kappaB signaling pathway, but also
      uncovers a new mechanism of crosstalk between NF-kappaB signaling and autophagy
      pathways.

PMID- 29044192
TI  - Skin transcriptome reveals the intrinsic molecular mechanisms underlying hair
      follicle cycling in Cashmere goats under natural and shortened photoperiod
      conditions.
AB  - The growth of cashmere exhibits a seasonal pattern arising from photoperiod
      change. However, the underlying molecular mechanism remains unclear. We profiled
      the skin transcriptome of six goats at seven time points during hair follicle
      cycling via RNA-seq. The six goats comprised three goats exposed to a natural
      photoperiod and three exposed to a shortened photoperiod. During hair cycle
      transition, 1713 genes showed differential expression, and 332 genes showed a
      pattern of periodic expression. Moreover, a short photoperiod induced the hair
      follicle to enter anagen early, and 246 genes overlapped with the periodic genes.
      Among these key genes, cold-shock domain containing C2 (CSDC2) was highly
      expressed in the epidermis and dermis of Cashmere goat skin, although its
      function in hair-follicle development remains unknown. CSDC2 silencing in mouse
      fibroblasts resulted in the decreased mRNA expression of two key hair-follicle
      factors, leading to reduced cell numbers and a lower cell density. Cashmere
      growth or molting might be controlled by a set of periodic regulatory genes. The
      appropriate management of short light exposure can induce hair follicles to enter
      full anagen early through the activation of these regulators. The CSDC2 gene is a
      potentially important transcription factor in the hair growth cycle.

PMID- 29044193
TI  - Effect of surface and internal defects on the mechanical properties of metallic
      glasses.
AB  - Despite the significance of surface effects on the deformation behaviours of
      small-scale metallic glasses, systematic investigations on surface states are
      lacking. In this work, by employing atomistic simulations, we characterise the
      distributions of local inhomogeneity near surfaces created by casting and
      cutting, along with internal distributions in pristine and irradiated bulk
      specimens, and investigate the effects of inhomogeneity on the mechanical
      properties. The cast surface shows enhanced yield strength and degrees of shear
      localisation, while the cut surface shows the opposite effects, although the
      fraction of vibrational soft spots, known to indicate low-energy barriers for
      local rearrangement, is high near both surfaces. Correspondingly, plastic
      deformation is initiated near the cut surface, but far from the cast surface. We
      reveal that improved local orientational symmetry promotes strengthening in cast
      surfaces and originates from the effectively lower quenching rate due to faster
      diffusion near the surface. However, a significant correlation among vibrational
      soft spots, local symmetries, and the degree of shear localisation is found for
      the pristine and irradiated bulk materials. Our findings reveal the sensitivity
      of the surface state to the surface preparation methods, and indicate that
      particular care must be taken when studying metallic glasses containing free
      surfaces.

PMID- 29044194
TI  - Response to: 'Lack of evidence for Zika virus transmission by Culex mosquitoes'.

PMID- 29044195
TI  - Lack of evidence for Zika virus transmission by Culex mosquitoes.

PMID- 29044196
TI  - Exercise and high-fat feeding remodel transcript-metabolite interactive networks
      in mouse skeletal muscle.
AB  - Enhanced coverage and sensitivity of next-generation 'omic' platforms has allowed
      the characterization of gene, metabolite and protein responses in highly
      metabolic tissues, such as, skeletal muscle. A limitation, however, is the
      capability to determine interaction between dynamic biological networks. To
      address this limitation, we applied Weighted Analyte Correlation Network Analysis
      (WACNA) to RNA-seq and metabolomic datasets to identify correlated subnetworks of
      transcripts and metabolites in response to a high-fat diet (HFD)-induced obesity
      and/or exercise. HFD altered skeletal muscle lipid profiles and up-regulated
      genes involved in lipid catabolism, while decreasing 241 exercise-responsive
      genes related to skeletal muscle plasticity. WACNA identified the interplay
      between transcript and metabolite subnetworks linked to lipid metabolism,
      inflammation and glycerophospholipid metabolism that were associated with IL6,
      AMPK and PPAR signal pathways. Collectively, this novel experimental approach
      provides an integrative resource to study transcriptional and metabolic networks
      in skeletal muscle in the context of health and disease.

PMID- 29044197
TI  - Development of a multiplex probe combination-based one-step real-time reverse
      transcription-PCR for NA subtype typing of avian influenza virus.
AB  - Nine influenza virus neuraminidase (NA) subtypes have been identified in poultry
      and wild birds. Few methods are available for rapid and simple NA subtyping. Here
      we developed a multiplex probe combination-based one-step real-time reverse
      transcriptase PCR (rRT-PCR) to detect nine avian influenza virus NA subtypes.
      Nine primer-probe pairs were assigned to three groups based on the different
      fluorescent dyes of the probes (FAM, HEX, or Texas Red). Each probe detected only
      one NA subtype, without cross reactivity. The detection limit was less than 100
      EID50 or 100 copies of cDNA per reaction. Data obtained using this method with
      allantoic fluid samples isolated from live bird markets and H9N2-infected
      chickens correlated well with data obtained using virus isolation and sequencing,
      but was more sensitive. This new method provides a specific and sensitive
      alternative to conventional NA-subtyping methods.

PMID- 29044198
TI  - Transgenic mice lacking CREB and CREM in noradrenergic and serotonergic neurons
      respond differently to common antidepressants on tail suspension test.
AB  - Evidence exists that chronic antidepressant therapy enhances CREB levels and
      activity. Nevertheless, the data are not conclusive, as previous analysis of
      transgenic mouse models has suggested that CREB inactivation in fact contributes
      to antidepressant-like behavior. The aim of this study was to evaluate the role
      of CREB in this context by exploiting novel transgenic mouse models,
      characterized by selective ablation of CREB restricted to noradrenergic
      (Creb1DBHCre/Crem-/-) or serotonergic (Creb1TPH2CreERT2/Crem-/-) neurons in a
      CREM-deficient background to avoid possible compensatory effects of CREM.
      Selective and functional ablation of CREB affected antidepressant-like behavior
      in a tail suspension test (TST) after antidepressant treatment. Contrary to
      single Creb1DBHCre mutants, Creb1DBHCre/Crem-/- mice did not respond to acute
      desipramine administration (20 mg/kg) on the TST. On the other hand, single
      Creb1TPH2CreERT2 mutants displayed reduced responses to fluoxetine (10 mg/kg) on
      the TST, while the effects in Creb1TPH2CreERT2/Crem-/- mice differed by gender.
      Our results provide further evidence for the important role of CREM as a
      compensatory factor. Additionally, the results indicate that new models based on
      the functional ablation of CREB in select neuronal populations may represent a
      valuable tool for investigating the role of CREB in the mechanism of
      antidepressant therapy.

PMID- 29044199
TI  - Fluorescence-coded DNA Nanostructure Probe System to Enable Discrimination of
      Tumor Heterogeneity via a Screening of Dual Intracellular microRNA Signatures in
      situ.
AB  - Since the delivery kinetics of different cell types are different, the signal
      from the target cell is greatly affected by the noise signal of the diagnostic
      system. This is a major obstacle hindering the practical application of
      intracellular diagnostic systems, such as tumor heterogeneity. To address these
      issues, here we present a microRNA detection platform using fluorescence-encoded
      nanostructured DNA-based probes. The nanostructured DNA was designed to include
      molecular beacons for detecting cytosolic microRNA as well as additional
      fluorophores. When the intracellular diagnostic system is delivered, fluorescence
      signals are generated by the molecular beacons, depending on the concentration of
      the target microRNA. The fluorescence signals are then normalized to the
      intensity of the additional fluorophore. Through this simple calculation, the
      concentration of intracellular microRNA can be determined without interference
      from the diagnosis system itself. And also it enabled discrimination of microRNA
      expression heterogeneity in five different breast cancer cell lines.

PMID- 29044200
TI  - Up-regulation of casein kinase 1epsilon is involved in tau pathogenesis in
      Alzheimer's disease.
AB  - Hyperphosphorylation of tau and imbalanced expression of 3R-tau and 4R-tau as a
      result of dysregulation of tau exon 10 splicing are believed to be pivotal to the
      pathogenesis of tau pathology, but the molecular mechanism leading to the
      pathologic tau formation in Alzheimer's disease (AD) brain is not fully
      understood. In the present study, we found that casein kinase 1epsilon
      (CK1epsilon) was increased significantly in AD brains. Overexpression of
      CK1epsilon in cultured cells led to increased tau phosphorylation at many sites.
      Moreover, we found that CK1epsilon suppressed tau exon 10 inclusion. Levels of
      CK1epsilon were positively correlated to tau phosphorylation, 3R-tau expression
      and tau pathology, and negatively correlated to 4R-tau in AD brains.
      Overexpression of CK1epsilon in the mouse hippocampus increased tau
      phosphorylation and impaired spontaneous alternation behavior. These data suggest
      that CK1epsilon is involved in the regulation of tau phosphorylation, the
      alternative splicing of tau exon 10, and cognitive performance. Up-regulation of
      CK1epsilon might contribute to tau pathology by hyperphosphorylating tau and by
      dysregulating the alternative splicing of tau exon 10 in AD.

PMID- 29044201
TI  - Macrophage polarization and function: new prospects for fibrotic disease.
AB  - Fibrosis is commonly regarded as a pathological and dynamic process with the
      hallmarks of chronic inflammation and wound healing. Emerging evidence indicates
      that heterogeneous monocyte-macrophage lineage cells are indispensable for
      mounting either pro-fibrotic or anti-fibrotic responses in different stages
      during fibrotic pathogenesis. This review highlights the evolving roles of
      macrophage polarization and functions linked to fibrosis in multiple organs. In
      the future, identifying the molecular and cellular factors that influence the
      macrophage phenotypic balance may provide novel therapeutic approaches for
      fibrotic diseases.

PMID- 29044202
TI  - The Effects of Exoskeleton Assisted Knee Extension on Lower-Extremity Gait
      Kinematics, Kinetics, and Muscle Activity in Children with Cerebral Palsy.
AB  - Individuals with cerebral palsy often exhibit crouch gait, a debilitating and
      inefficient walking pattern marked by excessive knee flexion that worsens with
      age. To address the need for improved treatment, we sought to evaluate if
      providing external knee extension assistance could reduce the excessive burden
      placed on the knee extensor muscles as measured by knee moments. We evaluated a
      novel pediatric exoskeleton designed to provide appropriately-timed extensor
      torque to the knee joint during walking in a multi-week exploratory clinical
      study. Seven individuals (5-19 years) with mild-moderate crouch gait from
      cerebral palsy (GMFCS I-II) completed the study. For six participants, powered
      knee extension assistance favorably reduced the excessive stance-phase knee
      extensor moment present during crouch gait by a mean of 35% in early stance and
      76% in late stance. Peak stance-phase knee and hip extension increased by 12
      degrees  and 8 degrees , respectively. Knee extensor muscle activity decreased
      slightly during exoskeleton-assisted walking compared to baseline, while knee
      flexor activity was elevated in some participants. These findings support the use
      of wearable exoskeletons for the management of crouch gait and provide insights
      into their future implementation.

PMID- 29044203
TI  - Neomorphosis and heterochrony of skull shape in dog domestication.
AB  - The overall similarity of the skull shape of some dog breeds with that of
      juvenile wolves begs the question if and how ontogenetic changes such as
      paedomorphosis (evolutionary juvenilisation) played a role in domestication. Here
      we test for changes in patterns of development and growth during dog
      domestication. We present the first geometric morphometric study using
      ontogenetic series of dog and wolf crania, and samples of dogs with relatively
      ancestral morphology and from different time periods. We show that patterns of
      juvenile-to-adult morphological change are largely similar in wolves and domestic
      dogs, but differ in two ways. First, dog skulls show unique (neomorphic) features
      already shortly after birth, and these features persist throughout postnatal
      ontogeny. Second, at any given age, juvenile dogs exhibit skull shapes that
      resemble those of consistently younger wolves, even in dog breeds that do not
      exhibit a 'juvenilized' morphology as adults. These patterns exemplify the
      complex nature of evolutionary changes during dog domestication: the cranial
      morphology of adult dogs cannot simply be explained as either neomorphic or
      paedomorphic. The key to our understanding of dog domestication may lie in a
      closer comparative examination of developmental phases.

PMID- 29044204
TI  - Collimated protons accelerated from an overdense gas jet irradiated by a 1 um
      wavelength high-intensity short-pulse laser.
AB  - We have investigated proton acceleration in the forward direction from a near
      critical density hydrogen gas jet target irradiated by a high intensity (1018
      W/cm2), short-pulse (5 ps) laser with wavelength of 1.054 MUm. We observed the
      signature of the Collisionless Shock Acceleration mechanism, namely quasi
      monoenergetic proton beams with small divergence in addition to the more commonly
      observed electron-sheath driven proton acceleration. The proton energies we
      obtained were modest (~MeV), but prospects for improvement are offered through
      further tailoring the gas jet density profile. Also, we observed that this
      mechanism is very robust in producing those beams and thus can be considered as a
      future candidate in laser-driven ion sources driven by the upcoming next
      generation of multi-PW near-infrared lasers.

PMID- 29044205
TI  - Gender Differences in Behavioral and Neural Responses to Unfairness Under Social
      Pressure.
AB  - Numerous studies have revealed the key role of social pressure on individuals'
      decision-making processes. However, the impact of social pressure on unfairness
      related decision-making processes remains unclear. In the present study, we
      investigated how social pressure modulated men's and women's responses in an
      ultimatum game. Twenty women and eighteen men played the ultimatum game as
      responders in the scanner, where fair and unfair offers were tendered by
      proposers acting alone (low pressure) or by proposers endorsed by three
      supporters (high pressure). Results showed that men rejected more, whereas women
      accepted more unfair offers in the high versus low pressure context. Neurally,
      pregenual anterior cingulate cortex activation in women positively predicted
      their acceptance rate difference between contexts. In men, stronger right
      anterior insula activation and increased connectivity between right anterior
      insula and dorsal anterior cingulate cortex were observed when they receiving
      unfair offers in the high than low pressure context. Furthermore, more bilateral
      anterior insula and left dorsolateral prefrontal cortex activations were found
      when men rejected (relative to accepted) unfair offers in the high than low
      pressure context. These findings highlighted gender differences in the modulation
      of behavioral and neural responses to unfairness by social pressure.

PMID- 29044206
TI  - Emergence of the Stoner-Wohlfarth astroid in thin films at dynamic regime.
AB  - The Stoner-Wohlfarth (SW) model is the simplest model that describes adequately
      the magnetization reversal of nanoscale systems that are small enough to contain
      single magnetic domains. However for larger sizes where multi-domain effects are
      present, e.g., in thin films, this simple macrospin approximation fails and the
      experimental critical curve, referred as SW astroid, is far from its predictions.
      Here we show that this discrepancy could vanish also in extended system. We
      present a detailed angular-dependent study of magnetization reversal dynamics of
      a thin film with well-defined uniaxial magnetic anisotropy, performed over 9
      decades of applied field sweep rate (dH/dt). The angular-dependent properties
      display a gradual transition from domain wall pinning and motion-like behaviour
      to a nucleative single-particle one, as dH/dt increases. Remarkably, in the high
      dynamic regime, where nucleation of reversed domains is the dominant mechanism of
      the magnetization reversal (nucleative regime), the magnetic properties including
      the astroid become closer to the ones predicted by SW model. The results also
      show why the SW model can successfully describe other extended systems that
      present nucleative regime, even in quasi-static conditions.

PMID- 29044207
TI  - Demographic history and biologically relevant genetic variation of Native
      Mexicans inferred from whole-genome sequencing.
AB  - Understanding the genetic structure of Native American populations is important
      to clarify their diversity, demographic history, and to identify genetic factors
      relevant for biomedical traits. Here, we show a demographic history
      reconstruction from 12 Native American whole genomes belonging to six distinct
      ethnic groups representing the three main described genetic clusters of Mexico
      (Northern, Southern, and Maya). Effective population size estimates of all Native
      American groups remained below 2,000 individuals for up to 10,000 years ago. The
      proportion of missense variants predicted as damaging is higher for undescribed
      (~ 30%) than for previously reported variants (~ 15%). Several variants
      previously associated with biological traits are highly frequent in the Native
      American genomes. These findings suggest that the demographic and adaptive
      processes that occurred in these groups shaped their genetic architecture and
      could have implications in biological processes of the Native Americans and
      Mestizos of today.

PMID- 29044208
TI  - Growth factors regulate phospholipid biosynthesis in human fibroblast-like
      synoviocytes obtained from osteoarthritic knees.
AB  - Elevated levels of growth factors and phospholipids (PLs) have been found in
      osteoarthritic synovial fluid (SF), although the metabolic regulation of PLs is
      currently unknown. This study aimed to determine the effects of growth factors on
      the biosynthesis of PLs by fibroblast-like synoviocytes (FLS) obtained from human
      osteoarthritic knee joints. Electrospray ionization tandem mass spectrometry was
      applied to analyse the newly synthesized PLs. In the presence of stable isotope
      labelled PL precursors, cultured FLS were treated with either transforming growth
      factor-beta1 (TGF-beta1), bone morphogenetic protein (BMP)-2, BMP-4, BMP-7 or
      insulin-like growth factor-1 (IGF-1) alone or in combination with specific
      inhibitors of cell signalling pathways. TGF-beta1 and IGF-1 markedly stimulated
      the biosynthesis of phosphatidylcholine (PC) before sphingomyelin (SM) and
      lysophosphatidylcholine (LPC) species were stimulated. BMPs elaborated less
      pronounced effects. The BMPs tested have different potentials to induce the
      biosynthesis of phosphatidylethanolamine (PE) and PE-based plasmalogens. Our
      study shows for the first time that TGF-beta1 and IGF-1 substantially regulate
      the biosynthesis of PC, SM and LPC in human FLS. The functional consequences of
      elevated levels of PLs require additional study. The BMPs tested may be joint
      protective in that they upregulate PE-based plasmalogens that function as
      endogenous antioxidants against reactive oxygen species.

PMID- 29044209
TI  - Cell-penetrating interactomic inhibition of nuclear factor-kappa B in a mouse
      model of postoperative cognitive dysfunction.
AB  - Some patients experience impaired cognitive functioning after surgery, a
      phenomenon referred to as postoperative cognitive dysfunction (POCD). Signs of
      POCD are closely associated with the development of systemic or hippocampal
      inflammation. However, the precise pathophysiological mechanisms of
      prevention/treatment options for POCD still remain unclear. After injury, the
      transcriptional factor nuclear factor-kappa B (NF-kappaB) is thought to regulate
      or stimulate inflammation amplification. Therefore, we designed a cell
      penetrating fusion protein called nt-p65-TMD, which inhibits NF-kappaB p65
      activation by translocating into the nucleus. In the present study, we discovered
      that nt-p65-TMD exerted effects on surgery-induced cognitive impairment in mice.
      Specifically, nt-p65-TMD exhibited strong immunoregulatory properties that were
      able to reduce surgery-induced elevations in cerebrovascular integrity
      impairment, subsequent peripheral immune-cell recruitment, and inflammation
      amplification, which ultimately lead to cognitive decline. The nt-p65-TMD has the
      unique ability to regulate and reduce systemic inflammation and inflammation
      amplification, suggesting a new strategy for preventing development of cognitive
      decline that occurs in POCD.

PMID- 29044210
TI  - Calmodulin confers calcium sensitivity to the stability of the distal
      intracellular assembly domain of Kv7.2 channels.
AB  - Tetrameric coiled-coil structures are present in many ion channels, often
      adjacent to a calmodulin (CaM) binding site, although the relationship between
      the two is not completely understood. Here we examine the dynamic properties of
      the ABCD domain located in the intracellular C-terminus of tetrameric, voltage
      dependent, potassium selective Kv7.2 channels. This domain encompasses the CaM
      binding site formed by helices A and B, followed by helix C, which is linked to
      the helix D coiled-coil. The data reveals that helix D stabilizes CaM binding,
      promoting trans-binding (CaM embracing neighboring subunits), and they suggest
      that the ABCD domain can be exchanged between subunits of the tetramer. Exchange
      is faster when mutations in AB weaken the CaM interaction. The exchange of ABCD
      domains is slower in the presence of Ca2+, indicating that CaM stabilization of
      the tetrameric assembly is enhanced when loaded with this cation. Our
      observations are consistent with a model that involves a dynamic mechanism of
      helix D assembly, which supports reciprocal allosteric coupling between the A-B
      module and the coiled-coil formed by the helix D. Thus, formation of the distal
      helix D tetramer influences CaM binding and CaM-dependent Kv7.2 properties,
      whereas reciprocally, CaM and Ca2+ influence the dynamic behavior of the helix D
      coiled-coil.

PMID- 29044211
TI  - Identification of novel mazEF/pemIK family toxin-antitoxin loci and their
      distribution in the Staphylococcus genus.
AB  - The versatile roles of toxin-antitoxin (TA) systems in bacterial physiology and
      pathogenesis have been investigated for more than three decades. Diverse TA loci
      in Bacteria and Archaea have been identified in genome-wide studies. The advent
      of massive parallel sequencing has substantially expanded the number of known
      bacterial genomic sequences over the last 5 years. In staphylococci, this has
      translated into an impressive increase from a few tens to a several thousands of
      available genomes, which has allowed us for the re-evalution of prior
      conclusions. In this study, we analysed the distribution of mazEF/pemIK family TA
      system operons in available staphylococcal genomes and their prevalence in mobile
      genetic elements. 10 novel m azEF/pemIK homologues were identified, each with a
      corresponding toxin that plays a potentially different and undetermined
      physiological role. A detailed characterisation of these TA systems would be
      exceptionally useful. Of particular interest are those associated with an SCCmec
      mobile genetic element (responsible for multidrug resistance transmission) or
      representing the joint horizontal transfer of TA systems and determinants of
      vancomycin resistance from enterococci. The involvement of TA systems in
      maintaining mobile genetic elements and the associations between novel
      mazEF/pemIK loci and those which carry drug resistance genes highlight their
      potential medical importance.

PMID- 29044212
TI  - A Pilot Study on Tocilizumab for Treating Refractory Adult-Onset Still's Disease.
AB  - To investigate the efficacy and safety of Tocilizumab (TCZ) in patients with
      refractory adult-onset Still's disease (AOSD). We enrolled 8 female patients from
      October 2013 to July 2014. All patients fulfilled Japan's Yamaguch AOSD
      classification and recognized as refractory AOSD. All Patients received TCZ
      treatment 4-8 mg/kg every 4 weeks. Evaluation of efficacy was conducted after 3
      months and 6 months, including clinical manifestations of AOSD patients,
      improvement of inflammatory markers as well as glucocorticoids dosage
      adjustments. Treatment-related adverse events were also recorded. Patients
      treated with Tocilizumab with average age 41.1 years old, the average disease
      duration 23.6 months. Two patients drop off due to infusion side effects. Others
      were followed at least 6 months. After 3 months of follow-up, remission rates of
      fever, arthritis and rashes from 8 patients were 87.5%, 100% and 87.5%. White
      blood cell counts, erythrocyte sedimentation rate, C-reactive protein and
      ferritin levels were decreased (P < 0.01) significantly compared to treatment
      before. Furthermore, the average dose of prednisone was reduced from 51.7 +/-
      38.4 mg/d to 12.9 +/- 7.7 mg/d (P < 0.01). Our findings suggest that tocilizumab
      could alleviate the clinical manifestations of refractory AOSD rapidly and
      efficiently.

PMID- 29044213
TI  - Prediction of Deterministic All-Optical Switching of Ferromagnetic Thin Film by
      Ultrafast Optothermal and Optomagnetic Couplings.
AB  - All-optical switching (AOS) of magnetization induced by ultrafast laser pulses is
      fundamentally interesting and promises unprecedented speed for magnetic data
      storage that is three orders of magnitudes faster than the current techniques.
      For ferrimagnetic material, the AOS is attributed to magnetic circular dichroism
      and angular momentum transfer between sublattices. Recently, ferromagnetic
      material is demonstrated in AOS under multiple pulses. Since the magnetic field
      needed to flip the ferromagnetic magnetization within femtosecond timescale is
      unphysically high, some theories hypothesized that there exists a prolonged
      magnetic field beyond the pulse duration in the switching process. This is
      intuitively inconsistent with the phenomenological explanation based on the light
      induced magnetic field arising from the inverse Faraday effect (IFE). Here, we
      numerically study the AOS process and provide new insights into the long-standing
      paradox of the duration of the induced magnetic field. We show that the prolonged
      magnetic field duration originates from the ultrafast optothermal and
      optomagnetic coupling. Moreover, we numerically studied both single- and multiple
      pulse AOS under different coupling strength between spins and the thermal bath in
      the macroscopic Fockker-Planck and Landau-Lifshitz-Bloch model. This numerical
      model may provide a guide to find suitable ferromagnetic materials for AOS.

PMID- 29044214
TI  - Limits of aerobic metabolism in cancer cells.
AB  - Cancer cells exhibit high rates of glycolysis and glutaminolysis. Glycolysis can
      provide energy and glutaminolysis can provide carbon for anaplerosis and
      reductive carboxylation to citrate. However, all these metabolic requirements
      could be in principle satisfied from glucose. Here we investigate why cancer
      cells do not satisfy their metabolic demands using aerobic biosynthesis from
      glucose. Based on the typical composition of a mammalian cell we quantify the
      energy demand and the OxPhos burden of cell biosynthesis from glucose. Our
      calculation demonstrates that aerobic growth from glucose is feasible up to a
      minimum doubling time that is proportional to the OxPhos burden and inversely
      proportional to the mitochondria OxPhos capacity. To grow faster cancer cells
      must activate aerobic glycolysis for energy generation and uncouple NADH
      generation from biosynthesis. To uncouple biosynthesis from NADH generation
      cancer cells can synthesize lipids from carbon sources that do not produce NADH
      in their catabolism, including acetate and the amino acids glutamate, glutamine,
      phenylalanine and tyrosine. Finally, we show that cancer cell lines have an
      OxPhos capacity that is insufficient to support aerobic biosynthesis from
      glucose. We conclude that selection for high rate of biosynthesis implies a
      selection for aerobic glycolysis and uncoupling biosynthesis from NADH
      generation.

PMID- 29044215
TI  - New magnetostratigraphic evidence for the age of Acheulean tools at the archaeo
      palaeontological site "Solana del Zamborino" (Guadix - Baza Basin, S Spain).
AB  - The sedimentary record in the Guadix-Baza Basin (southern Spain) has proved to be
      a great source of information for the Miocene through the Pleistocene periods,
      due to the abundant faunal remains preserved, in some cases associated with
      lithic tools. The Solana del Zamborino (SZ) section has been the subject of
      controversy ever since a magnetostratigraphic analysis resulted in an age of 750
      770 Kyr for Acheulean tools, a chronology significantly older than the ~600 Kyr
      established chronology for the first Acheulean record in Europe. Although recent
      findings at the "Barranc de la Boella" site (north-east of the Iberian Peninsula)
      seem to indicate that an earlier introduction of such technique in Europe around
      0.96-0.781 Ma is possible, the precise age of the classical site at SZ is still
      controversial. The aim of this paper is to constrain the chronology of the site
      by developing a longer magnetostratigraphic record. For this purpose, we carried
      out an exhaustive sampling in a new succession at SZ. Our results provide a ~65 m
      magnetostratigraphic record in which 4 magnetozones of normal polarity are found.
      Our new magnetostratigraphic data suggest an age range between 300-480 Kyr for
      the lithic tools, closer to the age of traditional Acheulean sites in Europe.

PMID- 29044216
TI  - Association between Parkinson's disease and risk of prostate cancer in different
      populations: An updated meta-analysis.
AB  - Recently, growing evidence has revealed a significant association between
      Parkinson's disease (PD) and cancer. However, controversy still exists concerning
      the association between PD and prostate cancer. A comprehensive article search
      for relevant published studies was performed using the online databases PubMed,
      Web of Science and Embase up to January 1, 2017. The pooled risk ratios (RRs) and
      their 95% confidence intervals (CIs) were calculated using the method of inverse
      variance with a random-effects model. Fifteen studies comprising 346,153 PD
      patients were included in this study. The results of the present study showed
      that PD was significantly associated with a decreased risk of prostate cancer in
      the Western population (RR: 0.83, 95% CI: 0.72-0.95, P < 0.01), while an
      increased risk of prostate cancer was shown in the Asian population (RR: 1.80,
      95% CI: 1.52-2.13, P < 0.001). In the subgroup analysis, the reduced risk of
      prostate cancer in PD patients from Western populations was consistent regardless
      of study design or study quality. In conclusion, PD was significantly associated
      with a reduced risk of prostate cancer in the Western population. The
      relationship between those conditions in the Asian population needs to be
      confirmed by future studies.

PMID- 29044217
TI  - Molecular structure of starch isolated from jackfruit and its relationship with
      physicochemical properties.
AB  - The molecular structure of starches isolated from five jackfruits (M2, M3, M4, M8
      and X1) and its relationship with physicochemical properties were investigated.
      Although they had uniform amylose (AM) content, the five jackfruit starches
      displayed different physicochemical properties, including their pasting, thermal,
      crystal and texture properties. Furthermore, differences in the molecular
      structure (i.e., average weight-average molar mass (Mw) of amylose and
      amylopectin (AP) as well as the same AP fine structure) were also found in the
      five jackfruit starches. The results indicated that jackfruit starch with a
      larger Mw of amylose and proportions of DP 25-36, DP >= 37 and chain length had a
      lower peak viscosity, breakdown, final viscosity, setback and adhesiveness, but a
      higher pasting and gelatinization temperature, gelatinization temperature range,
      gelatinization enthalpy and relative crystallinity. Xiangyinsuo 1 hao (X1)
      starch, which originated from Xinglong in Hainan province, China, had special
      physicochemical properties, which were ascribed to its lower amylopectin Mw,
      smaller particle size, and perfect amylopectin structure. The results showed that
      the most important intrinsic factors that could determine the physicochemical
      properties of starch were its molecular structure, including the Mw of amylose
      and AP as well as a fine AP structure.

PMID- 29044218
TI  - Wax Ester Synthase/Diacylglycerol Acyltransferase Isoenzymes Play a Pivotal Role
      in Wax Ester Biosynthesis in Euglena gracilis.
AB  - Wax ester fermentation is a unique energy gaining pathway for a unicellular
      phytoflagellated protozoan, Euglena gracilis, to survive under anaerobiosis. Wax
      esters produced in E. gracilis are composed of saturated fatty acids and
      alcohols, which are the major constituents of myristic acid and myristyl alcohol.
      Thus, wax esters can be promising alternative biofuels. Here, we report the
      identification and characterization of wax ester synthase/diacylglycerol
      acyltrasferase (WSD) isoenzymes as the terminal enzymes of wax ester production
      in E. gracilis. Among six possible Euglena WSD orthologs predicted by BLASTX
      search, gene expression analysis and in vivo evaluation for enzyme activity with
      yeast expressing individual recombinant WSDs indicated that two of them (EgWSD2
      and EgWSD5) predominantly function as wax ester synthase. Furthermore,
      experiments with gene silencing demonstrated a pivotal role of both EgWSD2 and
      EgWSD5 in wax ester synthesis, as evidenced by remarkably reduced wax ester
      contents in EgWSD2/5-double knockdown E. gracilis cells treated with anaerobic
      conditions. Interestingly, the decreased ability to produce wax ester did not
      affect adaptation of E. gracilis to anaerobiosis. Lipid profile analysis
      suggested allocation of metabolites to other compounds including triacylglycerol
      instead of wax esters.

PMID- 29044219
TI  - Association of anaemia with Helicobacter pylori infection: a retrospective study.
AB  - The role of Helicobacter pylori (H. pylori) infection in haematological system
      diseases is not well understood. We conducted this retrospective study to explore
      the association between H. pylori infection and anaemia in the Chinese
      population. This retrospective study was performed in Aerospace Center Hospital
      in Beijing. We derived the data from the registration system of the physical
      population between 2012-2016. Logistic regression models were used to explore the
      association between H. pylori infection and anaemia. Among 17,791 subjects, there
      were 7,804 (43.9%) subjects with H. pylori infection and 950 (5.3%) with anaemia.
      The prevalence of anaemia in the H. pylori (+) group was significantly higher
      than in the H. pylori (-) group after adjusting for age, sex, marriage,
      underlying diseases and body mass index. Compared to H. pylori (-), the OR of H.
      pylori (+) was 1.39 for moderate-to-severe anaemia and 1.05 for mild anaemia. The
      level of haemoglobin was lower in the H. pylori (+) group than in the H. pylori (
      ) group. This study indicates that H. pylori infection may be related to anaemia
      and haemoglobin level in the Chinese population.

PMID- 29044220
TI  - Structure of melanins from the fungi Ochroconis lascauxensis and Ochroconis
      anomala contaminating rock art in the Lascaux Cave.
AB  - Two novel species of the fungal genus Ochroconis, O. lascauxensis and O. anomala
      have been isolated from the walls of the Lascaux Cave, France. The interest in
      these fungi and their melanins lies in the formation of black stains on the walls
      and rock art which threatens the integrity of the paintings. Here we report solid
      state cross polarization magic-angle spinning 13C and 15N nuclear magnetic
      resonance (NMR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) of
      the melanins extracted from the mycelia of O. lascauxensis and O. anomala in
      order to known their chemical structure. The melanins from these two species were
      compared with those from other fungi. The melanins from the Ochroconis species
      have similar SERS and 13C and 15N NMR spectra. Their chemical structures as
      suggested by the data are not related to 3,4-dihydroxyphenylalanine, 5,6
      dihydroxyindole or 1,8-dihydroxynaphthalene precursors and likely the building
      blocks from the melanins have to be based on other phenols that react with the N
      terminal amino acid of proteins. The analytical pyrolysis of the acid hydrolysed
      melanin from O. lascauxensis supports this assumption.

PMID- 29044221
TI  - Downregulation of miR-16 via URGCP pathway contributes to glioma growth.
AB  - Experimental and clinical evidence points to a critical role of Upregulator of
      cell proliferation (URGCP/URG4) in controlling the progression of multiple
      tumors. However, the oncogenic role of URGCP in glioma still remains elusive. In
      this study we tried to investigate the oncogenic roles and molecular mechanisms
      of URGCP in glioma. We found that the levels of URGCP were upregulated in glioma,
      and that the high-levels of URGCP indicated a worse prognosis in glioma patients.
      URGCP and miR-16 are critical for glioma growth: silencing URGCP (shURGCP)
      inhibited glioma growth, while, the shURGCP-mediated proliferative inhibition
      could be recovered by antagonizing miR-16 (anta-miR-16) in vivo and in vitro.
      Mechanically, URGCP repressed miR-16 expression via activating NF-kappaB/c-myc
      pathway in glioma; Cyclins D1 and Cyclin E1 were identified as the direct targets
      of miR-16, thus, URGCP-mediated miR-16 downregulation accelerated cell
      proliferation by upregulating Cyclin D1 and Cyclin E1 expression. All these
      results suggested that URGCP accelerates glioma growth through the NF-kappaB/c
      myc/miR-16/Cyclin D1/E1 pathway, and both URGCP and miR-16 function as a novel
      cell cycle regulators in glioma and could be considered as potential targets for
      glioma therapy.

PMID- 29044222
TI  - Rapid Generation and Detection of Biomimetic Oxygen Concentration Gradients In
      Vitro.
AB  - Hypoxic regions exist within most solid tumors and often lead to altered cellular
      metabolism, metastasis, and drug resistance. Reliable generation and detection of
      biomimetic gaseous gradients in vitro is challenging due to low spatiotemporal
      resolution and poor longevity of gradients utilizing microfluidic techniques.
      Here, we present a novel and simplistic approach for producing gradients of
      dissolved oxygen (DO) within a lab-on-a-chip platform. Linear and stable DO
      gradients with high spatial resolution are established by introducing pre-gassed
      media into the gradient generating network. An underlying platinum(ii)
      octaethlporphyrin ketone (PtOEPK) based sensor layer allows parallel detection of
      oxygen. A thin 3-sided glass coating on the inner channel walls prevents multi
      directional diffusion of ambient oxygen across PDMS preserving the gradient
      resolution and stability. Viability analysis of normal mammary epithelial cells
      (MCF-12A) under oxygen gradients revealed 70% mortality after 6 hours of hypoxic
      exposure. Biological applicability of the platform was further validated by
      demonstrating increase in endoplasmic reticulum stress of MDA-MB-468 cells with
      time and with increasing oxygen tension. The unique ability to establish parallel
      or opposing gradients of gases and chemicals offers the potential for a wide
      range of applications in therapeutic development, and fundamental understanding
      of cellular behavior during hypoxia.

PMID- 29044223
TI  - Modulating hemispheric lateralization by brain stimulation yields gain in mental
      and physical activity.
AB  - Imagery plays an important role in our life. Motor imagery is the mental
      simulation of a motor act without overt motor output. Previous studies have
      documented the effect of motor imagery practice. However, its translational
      potential for patients as well as for athletes, musicians and other groups,
      depends largely on the transfer from mental practice to overt physical
      performance. We used bilateral transcranial direct current stimulation (tDCS)
      over sensorimotor areas to modulate neural lateralization patterns induced by
      unilateral mental motor imagery and the performance of a physical motor task.
      Twenty-six healthy older adults participated (mean age = 67.1 years) in a double
      blind cross-over sham-controlled study. We found stimulation-related changes at
      the neural and behavioural level, which were polarity-dependent. Specifically,
      for the hand contralateral to the anode, electroencephalographic activity induced
      by motor imagery was more lateralized and motor performance improved. In
      contrast, for the hand contralateral to the cathode, hemispheric lateralization
      was reduced. The stimulation-related increase and decrease in neural
      lateralization were negatively related. Further, the degree of stimulation
      related change in neural lateralization correlated with the stimulation-related
      change on behavioural level. These convergent neurophysiological and behavioural
      effects underline the potential of tDCS to improve mental and physical motor
      performance.

PMID- 29044224
TI  - Crosstalk between proteins expression and lysine acetylation in response to
      patulin stress in Rhodotorula mucilaginosa.
AB  - The proteomic and lysine acetylation (Kac) changes, accompanying degradation of
      patulin in Rhodotorula mucilaginosa were analyzed using tandem mass tagging and
      N6-acetyllysine affinity enrichment followed by LC-MS/MS. Proteomic results
      showed that expression level of short-chain reductase protein and glutathione S
      transferase involved in detoxification was significantly up-regulated. In
      addition, the expression levels of zinc-binding oxidoreductase and quinone
      oxidoreductase that are involved in antioxidant process, ABC transport and MFS
      transport responsible for chemical transport were activated when treated with
      patulin. The quantitative real time PCR (qRT-PCR) result also indicated these
      genes expression levels were increased when treated with patulin. Kac changes
      accompanying degradation of patulin in R. mucilaginosa were also observed.
      Totally, 130 Kac sites in 103 proteins were differentially expressed under
      patulin stress. The differentially up expressed modified proteins were mainly
      involved in tricarboxylic acid cycle and nuclear acid biosynthesis. The
      differentially down expressed Kac proteins were mainly classified to ribosome,
      oxidative phosphorylation, protein synthesis and defense to stress process. Our
      results suggest that patulin exposure prompt R. mucilaginosa to produce a series
      of actions to resist or degrade patulin, including Kac. In addition, the Kac
      information in R. mucilaginosa and Kac in response to patulin stress was firstly
      revealed.

PMID- 29044225
TI  - microRNA-181b is increased in cystic fibrosis cells and impairs lipoxin A4
      receptor-dependent mechanisms of inflammation resolution and antimicrobial
      defense.
AB  - The involvement of microRNA (miR) in cystic fibrosis (CF) pathobiology is rapidly
      emerging. We previously documented that miR-181b controls the expression of the
      ALX/FPR2 receptor, which is recognized by the endogenous proresolution ligand,
      lipoxin (LX)A4. Here, we examined whether the miR-181b-ALX/FPR2 circuit was
      altered in CF. We examined human airways epithelial cells, normal (16HBE14o-),
      carrying the DeltaF508 mutation (CFBE41o-) or corrected for this mutation
      (CFBE41o-/CEP-CFTR wt 6.2 kb), as well as monocyte-derived macrophages (MPhis)
      from CF patients. CFBE41o- cells exhibited higher miR-181b and reduced ALX/FPR2
      levels compared to 16HBE14o- and CFBE41o-/CEP-CFTR wt 6.2 kb cells. An anti-mir
      181b significantly enhanced ALX/FPR2 expression (+ 60%) as well as LXA4-induced
      increase in transepithelial electric resistance (+ 25%) in CFBE41o- cells. MPhis
      from CF patients also displayed increased miR-181b (+ 100%) and lower ALX/FPR2
      levels (- 20%) compared to healthy cells. An anti-mir-181b enhanced ALX/FPR2
      expression (+ 40%) and normalized receptor-dependent LXA4-induced phagocytosis of
      fluorescent-labeled zymosan particles as well as of Pseudomonas aeruginosa by CF
      MPhis. These results provide the first evidence that miR-181b is overexpressed in
      CF cells, impairing some mechanisms of the ALX/FPR2-dependent pathway of
      inflammation resolution. Thus, targeting miR-181b may represent a strategy to
      enhance anti-inflammatory and anti-microbial defense mechanisms in CF.

PMID- 29044226
TI  - Bone marrow transplant-induced alterations in Notch signaling promote pathologic
      Th17 responses to gamma-herpesvirus infection.
AB  - Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication
      following hematopoietic stem cell transplantation (HSCT) characterized by severe
      pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow
      transplant (BMT) mice infected with murine gamma-herpesvirus-68 develop
      interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical
      manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are
      selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells
      isolated from lungs and spleens of infected BMT mice display Notch signaling
      defects. Mice transplanted with CD4-Cre-driven dominant-negative Notch
      transcriptional regulator Mastermind-Like (CD4-Cre-DNMAML (CCD) mice) bone marrow
      displayed elevated IL-17 and transforming growth factor-beta (TGF beta) in the
      lungs, a further expansion of T-helper type 17 (Th17) cells, and developed more
      fibrosis than wild-type (WT)-BMT mice. Culture of BMT lung leukocytes with
      recombinant Notch ligand, DLL4, restored Notch signaling and decreased production
      of IL-17. Adoptive transfer of CD11c+ DCs could restore Th1 and limit Th17 in WT
      BMT but not CCD-BMT mice, indicating that a specific DC/CD4+ T-cell Notch
      interaction modulates IL-17 production following reconstitution in syngeneic BMT
      mice. Given recent clinical observations showing that patients with pulmonary
      complications post-transplant harbor occult herpesvirus infections, these data
      provide mechanistic insight and suggest potential therapies for these devastating
      conditions.

PMID- 29044227
TI  - Accuracy of weight estimation by the Broselow tape is substantially improved by
      including a visual assessment of body habitus.
AB  - BackgroundThe Broselow tape (BT) has been shown to estimate weight poorly
      primarily because of variations in body habitus. The manufacturers have suggested
      that a visual assessment of habitus may be used to increase its performance. This
      study evaluated the ability of habitus-modified models to improve the accuracy
      thereof.MethodsA post hoc analysis of prospectively collected data from four
      hospitals in Johannesburg, South Africa, on a population of 1,085 children.
      Sixteen a priori models generated a modified weight estimation or drug dose based
      on the BT weight and a gestalt assessment of habitus.ResultsThe habitus-modified
      method suggested by the manufacturer did not improve the accuracy of the BT. Five
      dosing and four weight-estimation models were identified that markedly improved
      dosing and weight estimation accuracy, respectively. The best dosing model
      improved dosing accuracy (doses within 10% of correct dose) from 52.0 to 69.6%
      and reduced critical dosing errors from 16.5 to 4.3%. The best weight-estimation
      model improved accuracy from 59.4 to 81.9% and reduced critical errors from 11.8
      to 1.9%.ConclusionThe accuracy of the BT as a drug-dosing and weight-estimation
      device can be substantially improved by including an appraisal of body habitus in
      the methodology.

PMID- 29044228
TI  - Corrigendum: YAP antagonizes innate antiviral immunity and is targeted for
      lysosomal degradation through IKKE-mediated phosphorylation.
AB  - This corrects the article DOI: 10.1038/ni.3744.

PMID- 29044229
TI  - Breathe easy with neutrophils.

PMID- 29044231
TI  - Tim-3 promotes maternal tolerance.

PMID- 29044232
TI  - Neurodegenerative signature.

PMID- 29044230
TI  - Metabolic pressure and the breach of immunological self-tolerance.
AB  - The prevalence of autoimmune disorders in affluent countries has reached epidemic
      proportions. Over the past 50 years, a reverse trend between the frequency of
      infectious diseases and the incidence of autoimmune and allergic diseases led to
      the so-called 'hygiene hypothesis'. Given the epidemiological evidence and recent
      experimental data, we propose that this concept should also include metabolic
      pressure secondary to exposure to excessive daily caloric intake and
      overnutrition. We discuss how metabolic workload can modulate immunological
      tolerance and review the molecular mechanisms and the state of the art of the
      field. We also critically evaluate possibilities for restoring immunological
      homeostasis under conditions of metabolic pressure.

PMID- 29044233
TI  - Corrigendum: NLRP12 attenuates colon inflammation by maintaining colonic
      microbial diversity and promoting protective commensal bacterial growth.
AB  - This corrects the article DOI: 10.1038/ni.3690.

PMID- 29044234
TI  - CD28 enhances mitochondrial function.

PMID- 29044235
TI  - Corrigendum: The transcriptional coactivator TAZ regulates reciprocal
      differentiation of TH17 cells and Treg cells.
AB  - This corrects the article DOI: 10.1038/ni.3748.

PMID- 29044236
TI  - Cytokine-driven role of Srebps in killer cell metabolism.

PMID- 29044237
TI  - Corrigendum: IL-6 as a keystone cytokine in health and disease.
AB  - This corrects the article DOI: 10.1038/ni.3153.

PMID- 29044238
TI  - Addendum: Guidance of regulatory T cell development by Satb1-dependent super
      enhancer establishment.
AB  - This corrects the article DOI: 10.1038/ni.3646.

PMID- 29044239
TI  - Old fat macrophages.

PMID- 29044241
TI  - What is the point of the gallbladder?

PMID- 29044240
TI  - Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and
      protect against type 1 diabetes.
AB  - This corrects the article DOI: 10.1038/ni.3713.

PMID- 29044242
TI  - TFR cells trump autoimmune antibody responses to limit sedition.

PMID- 29044243
TI  - Killer T cells with a beta-flavi(r) for dengue.

PMID- 29044244
TI  - Corrigendum: The monogenic autoinflammatory diseases define new pathways in human
      innate immunity and inflammation.
AB  - This corrects the article DOI: 10.1038/ni.3777.

PMID- 29044245
TI  - Biomarkers of chronic inflammation in disease development and prevention:
      challenges and opportunities.

PMID- 29044246
TI  - FoxP3 partners up.

PMID- 29044249
TI  - Erratum to: Comparing the Efficiency of Two Different Extraction Techniques in
      Removal of Maxillary Third Molars: A Randomized Controlled Trial.
AB  - [This corrects the article DOI: 10.1007/s12663-016-0935-1.].

PMID- 29044247
TI  - Regulation of genome organization and gene expression by nuclear
      mechanotransduction.
AB  - It is well established that cells sense chemical signals from their local
      microenvironment and transduce them to the nucleus to regulate gene expression
      programmes. Although a number of experiments have shown that mechanical cues can
      also modulate gene expression, the underlying mechanisms are far from clear.
      Nevertheless, we are now beginning to understand how mechanical cues are
      transduced to the nucleus and how they influence nuclear mechanics, genome
      organization and transcription. In particular, recent progress in super
      resolution imaging, in genome-wide application of RNA sequencing, chromatin
      immunoprecipitation and chromosome conformation capture and in theoretical
      modelling of 3D genome organization enables the exploration of the relationship
      between cell mechanics, 3D chromatin configurations and transcription, thereby
      shedding new light on how mechanical forces regulate gene expression.

PMID- 29044250
TI  - Programmable fusion of liposomes mediated by lipidated PNA.
AB  - We recently reported a DNA-programmed fusion cascade enabling the use of
      liposomes as nanoreactors for compartmentalized chemical reactions. This
      communication reports an alternative and robust strategy based on lipidated
      peptide nucleic acids (LiPs). LiPs enabled fusion of liposomes with remarkable
      31% efficiency at 50  degrees C with low leakage (5%).

PMID- 29044248
TI  - Task demands, tDCS intensity, and the COMT val158met polymorphism impact tDCS
      linked working memory training gains.
AB  - Working memory (WM) training paired with transcranial direct current stimulation
      (tDCS) can improve executive function in older adults. The unclear mechanism of
      tDCS likely depends on tDCS intensity, and task relevant genetic factors (e.g.,
      for WM: COMT val158met, DAT, BDNF val66met). Higher tDCS intensity does not
      always lead to greater cognitive gains, and genetic polymorphisms may modulate
      tDCS-linked WM improvements. To evaluate these factors, 137 healthy older adults
      provided DNA samples and received Visual and Spatial WM training paired with tDCS
      (sham, 1, 1.5, 2 mA). After one session of tDCS, significant group differences in
      WM performance were predicted by COMT val158met status. One month after training,
      there was a significant interaction of tDCS intensity, COMT genotype, and WM
      task. Specifically, val/val homozygotes benefited most from 1.5 mA tDCS on Visual
      WM and from 1 mA tDCS on Spatial WM. For met/met homozygotes, 2 mA resulted in
      significantly poorer performance compared to 1.5 mA on Spatial WM. While this
      pattern was observed with relatively small sample sizes, these data indicate that
      variations in COMT val158met may predict the nature of WM improvement after
      initial and longitudinal tDCS. This contributes to our understanding of the
      underlying mechanism by which tDCS affects behaviour.

PMID- 29044251
TI  - Double C-S bond formation via C-H bond functionalization: synthesis of
      benzothiazoles and naphtho[2,1-d]thiazoles from N-substituted arylamines and
      elemental sulfur.
AB  - A novel, atom economic, and environmentally friendly method for the synthesis of
      2-substituted benzothiazoles and 2-substituted naphtho[2,1-d]thiazoles from N
      substituted arylamines and elemental sulfur has been developed under metal-free
      conditions. The reaction underwent the process of double C-S bond formation
      through C-H bond functionalization.

PMID- 29044252
TI  - Resistive memory devices based on a triphenylamine-decorated non-precious
      cobalt(ii) bis-terpyridine complex.
AB  - The ITO/active material/Au sandwiched devices of a cobalt(ii) bis-terpyridine
      complex decorated with two triphenylamine motifs display appealing flash-type
      resistive switching with a large ON/OFF ratio (>103) and low operating voltages
      (<+/-3 V). In contrast, devices with the triphenylamine-appended terpyridine
      ligand show WORM-type memory behaviour.

PMID- 29044253
TI  - Chromium doped Li2RuO3 as a positive electrode with superior electrochemical
      performance for lithium ion batteries.
AB  - Cr-Doped Li2RuO3 of the Li2Ru1-xCrxO3 (x = 0, 0.02, 0.05, 0.1) series was
      successfully synthesized and the effect of Cr on the electrochemical performance
      of Li2RuO3 was systematically investigated. The results show that
      Li2Ru0.95Cr0.05O3 exhibits the best performance in terms of capacity, rate
      capability and cycling stability.

PMID- 29044254
TI  - High stability of gold nanoparticles towards DNA modification and efficient
      hybridization via a surfactant-free peptide route.
AB  - With the assistance of peptides, a stable and highly efficient approach for the
      quick loading of thiol-DNA onto AuNPs is proposed with a high DNA utilization,
      which is generally applicable to specific DNA detection and diverse AuNP sizes.
      The maximum efficiency of hybridization reached 93% while the reaction time was
      shortened to 30 min.

PMID- 29044255
TI  - Roles of conformational disorder and downhill folding in modulating protein-DNA
      recognition.
AB  - Transcription factors are thought to efficiently search for their target DNA site
      via a combination of conventional 3D diffusion and 1D diffusion along the DNA
      molecule mediated by non-specific electrostatic interactions. This process
      requires the DNA-binding protein to quickly exchange between a search competent
      and a target recognition mode, but little is known as to how these two binding
      modes are encoded in the conformational properties of the protein. Here, we
      investigate this issue on the engrailed homeodomain (EngHD), a DNA-binding domain
      that folds ultrafast and exhibits a complex conformational behavior consistent
      with the downhill folding scenario. We explore the interplay between folding and
      DNA recognition using a coarse-grained computational model that allows us to
      manipulate the folding properties of the protein and monitor its non-specific and
      specific binding to DNA. We find that conformational disorder increases the
      search efficiency of EngHD by promoting a fast gliding search mode in addition to
      sliding. When gliding, EngHD remains loosely bound to DNA moving linearly along
      its length. A partially disordered EngHD also binds more dynamically to the
      target site, reducing the half-life of the specific complex via a spring-loaded
      mechanism. These findings apply to all conditions leading to partial disorder.
      However, we also find that at physiologically relevant temperatures EngHD is well
      folded and can only obtain the conformational flexibility required to accelerate
      1D diffusion when it folds/unfolds within the downhill scenario (crossing a
      marginal free energy barrier). In addition, the conformational flexibility of
      native downhill EngHD enables its fast reconfiguration to lock into the specific
      binding site upon arrival, thereby affording finer control of the on- and off
      rates of the specific complex. Our results provide key mechanistic insights into
      how DNA-binding domains optimize specific DNA recognition through the control of
      their conformational dynamics and folding mechanism.

PMID- 29044256
TI  - Interplay between the folding mechanism and binding modes in folding coupled to
      binding processes.
AB  - Proteins that fold upon binding to their partners exhibit complex binding
      behavior such as induced-fit. But the connections between the folding mechanism
      and the binding mode remain unknown. Here we focus on the high affinity complex
      between the physiologically and marginally unstable, fast folder PSBD and the E1
      subunit of pyruvate dehydrogenase. Using coarse-grained simulations we
      investigate the binding to E1 of a partially disordered PSBD under two folding
      scenarios: two-state and downhill. Our simulations show that induced-fit binding
      requires that PSBD folds-unfolds in the downhill folding regime. In contrast, a
      two-state folding PSBD must fold completely before it binds. The reason is that
      effective coupling between folding and binding involves partially folded
      conformations, which are only sufficiently populated under the downhill folding
      regime. Our results establish a direct mechanistic link between complex binding
      and downhill folding, supporting the idea that PSBD operates functionally as a
      conformational rheostat.

PMID- 29044257
TI  - Surface phase diagram prediction from a minimal number of DFT calculations: redox
      active adsorbates on zinc oxide.
AB  - Density functional theory (DFT) is routinely used to calculate the adsorption
      energies of molecules on solid surfaces, which can be employed to derive surface
      phase diagrams. Such calculations become computationally expensive if the number
      of substrate atoms is large, which happens whenever the adsorbate coverage is
      small. Here, we propose an efficient method for calculating surface phase
      diagrams for redox-active adsorbates on semiconductors, that we apply to the
      important example of proton (H+) and hydride (H-) adsorbates on a ZnO surface. We
      identify the leading cause for the coverage dependence of the adsorption energies
      to be the filling and depletion of the disperse substrate conduction band. From
      only four DFT calculations, coupled with an analysis of the substrate electronic
      band structure and changes in the electrostatic potential within the substrate
      upon adsorption, we derive a phenomenological model that well describes the
      coverage-dependent adsorption energies. Moreover, our model allows us to
      extrapolate to the "infinite" supercell limit, where additional H adsorption
      leads to an arbitrarily small increase of the surface coverage. With this tool we
      are able to derive a surface phase diagram containing structures with extremely
      small H coverages (<0.002 ML), that have so far been unattainable. We expect that
      such models can be applied to a wide range of semiconductor substrates and redox
      active adsorbates.

PMID- 29044258
TI  - The reaction of C5N- with acetylene as a possible intermediate step to produce
      large anions in Titan's ionosphere.
AB  - A theoretical and experimental investigation of the reaction C5N- + C2H2 has been
      carried out. This reaction is of astrophysical interest since the growth
      mechanism of large anions that have been detected in Titan's upper atmosphere by
      the Cassini plasma spectrometer are still largely unknown. The experimental
      studies have been performed using a tandem quadrupole mass spectrometer which
      allows identification of the different reaction channels and assessment of their
      reaction thresholds. Results of these investigations were compared with the
      predictions of ab initio calculations, which identified possible pathways leading
      to the observed products and their thermodynamical properties. These computations
      yielded that the majority of these products are only accessible via energy
      barriers situated more than 1 eV above the reactant energies. In many cases, the
      thresholds predicted by the ab initio calculations are in good agreement with the
      experimentally observed ones. For example, the chain elongation reaction leading
      to C7N-, although being slightly exoergic, possesses an energy barrier of 1.91
      eV. Therefore, the title reaction can be regarded to be somewhat unlikely to be
      responsible for the formation of large anions in cold environments such as
      interstellar medium or planetary ionospheres.

PMID- 29044260
TI  - Molecular engineering of organic electroactive materials for redox flow
      batteries.
AB  - With high scalability and independent control over energy and power, redox flow
      batteries (RFBs) stand out as an important large-scale energy storage system.
      However, the widespread application of conventional RFBs is limited by the
      uncompetitive performance, as well as the high cost and environmental concerns
      associated with the use of metal-based redox species. In consideration of
      advantageous features such as potentially low cost, vast molecular diversity, and
      highly tailorable properties, organic and organometallic molecules emerge as
      promising alternative electroactive species for building sustainable RFBs. This
      review presents a systematic molecular engineering scheme for designing these
      novel redox species. We provide detailed synthetic strategies for modifying the
      organic and organometallic redox species in terms of solubility, redox potential,
      and molecular size. Recent advances are then introduced covering the reaction
      mechanisms, specific functionalization methods, and electrochemical performances
      of redox species classified by their molecular structures. Finally, we conclude
      with an analysis of the current challenges and perspectives on future directions
      in this emerging research field.

PMID- 29044261
TI  - Dihydrobis(methimazolyl)borato complexes of ruthenium and osmium.
AB  - The reaction of Na[H2B(mt)2] (mt = 2-mercapto, 3-methylimidazol-1-yl,
      methimazolyl) with [Ru(X)Cl(CO)(PPh3)n] (n = 3 X = H; n = 2 BO2C6H4, SiCl3,
      SiMe3) affords the complexes [Ru(X)(CO)(PPh3){kappa2-H,S,S'-H2B(mt)2}]. Evidence
      is presented to also support the transient formation of [Ru(X)(CO)(PPh3){kappa2
      H,S,S'-H2B(mt)2}] (X = CH[double bond, length as m-dash]CHPh, Ph) via a similar
      strategy, although these are unstable. The osmium complex [OsH(CO)(PPh3){kappa2
      H,S,S'-H2B(mt)2}] is similarly obtained from [OsHCl(CO)(PPh3)3] or
      [OsH(NCMe)2(CO)(PPh3)2]BF4. The reaction of [RuH(CO)(PPh3){kappa2-H,S,S'
      H2B(mt)2}] with chloroform or diphenyldiselenide provides [Ru(X)(CO)(PPh3){kappa2
      H,S,S'-H2B(mt)2}] (X = Cl, SePh), the latter reaction also providing traces of
      [Ru(SeH)(CO)(PPh3){kappa2-H,S,S'-H2B(mt)2}]. Spectroscopic and structural data
      for the series [Ru(X)(CO)(PPh3){kappa2-H,S,S'-H2B(mt)2}] are discussed in terms
      of perturbations on the B-H-Ru interaction by the trans-ligand X.

PMID- 29044263
TI  - Structures, electron density and characterization of novel photocatalysts,
      (BaTaO2N)1-x(SrWO2N)x solid solutions.
AB  - Tungsten-modified barium tantalum oxynitride is a new visible-light photocatalyst
      for water oxidation. In the present work, novel barium tantalum strontium
      tungsten oxynitride solid solutions, (BaTaO2N)1-x(SrWO2N)x, with a cubic
      Pm3[combining macron]m perovskite-type structure (x = 0.01 and 0.02) have been
      prepared by heating oxide precursors under an ammonia flow. These (BaTaO2N)1
      x(SrWO2N)x catalysts exhibited photocatalytic water oxidation activity under
      visible light irradiation. The crystal structure, electron-density distribution,
      and optical properties of (BaTaO2N)1-x(SrWO2N)x (x = 0, 0.01, and 0.02) have been
      studied using synchrotron X-ray powder diffraction, Rietveld analysis, the
      maximum-entropy method (MEM), and UV-Vis reflectance measurements. The lattice
      parameters of (BaTaO2N)1-x(SrWO2N)x decreased linearly with increasing SrWO2N
      content x. The minimum electron density (MED) at the (Ta,W)-(O,N) bond,
      determined by the MEM analysis of (BaTaO2N)1-x(SrWO2N)x, increased with x, as
      supported by DFT-based calculations. These results indicate the formation of
      (BaTaO2N)1-x(SrWO2N)x solid solutions and enhanced covalent bonding due to the
      stronger W-N bond. The MED of the (Ta,W)-(O,N) bond was higher than that of
      (Ba,Sr)-(O,N), indicating that the (Ta,W)-(O,N) bond is more covalent. The
      presence of nitrogen in (BaTaO2N)1-x(SrWO2N)x was confirmed by the occupancy
      factor refined using neutron diffraction data and by the weight gain observed by
      thermogravimetric analysis in air. UV-Vis reflectance spectra and DFT
      calculations indicated that (BaTaO2N)1-x(SrWO2N)x contains W5+ cations with a
      [Xe] 4f14 5d1 electron configuration and exhibits a more n-type semiconducting
      character compared with BaTaO2N, which could improve the photocatalytic water
      oxidation activity under visible-light irradiation.

PMID- 29044265
TI  - A comprehensive review of the health perspectives of resveratrol.
AB  - Many natural products present in our diet, including flavonoids, can prevent the
      progression of cancer and other diseases. Resveratrol, a natural polyphenol
      present in various fruits and vegetables, plays an important role as a
      therapeutic and chemopreventive agent used in the treatment of various illnesses.
      It exhibits effects against different types of cancer through different pathways.
      It additionally exerts antidiabetic, anti-inflammatory, and anti-oxidant effects
      in a variety of cell types. Furthermore, the cardiovascular protective capacities
      of resveratrol are associated with multiple molecular targets and may lead to the
      development of novel therapeutic strategies for atherosclerosis,
      ischemia/reperfusion, metabolic syndrome, and heart failure. Accordingly, this
      article presents an overview of recent developments in the use of resveratrol for
      the prevention and treatment of different diseases along with various mechanisms.
      In addition, the present review summarizes the most recent literature pertaining
      to resveratrol as a chemotherapeutic agent against multiple diseases and provides
      an assessment of the potential of this natural compound as a complementary or
      alternative medicine.

PMID- 29044273
TI  - Doubling the power of DP4 for computational structure elucidation.
AB  - A large-scale optimisation of density functional theory (DFT) conditions for
      computational NMR structure elucidation has been conducted by systematically
      screening the DFT functionals and statistical models. The extended PyDP4 workflow
      was tested on a diverse and challenging set of 42 biologically active and
      stereochemically rich compounds, including highly flexible molecules.
      MMFF/mPW1PW91/M06-2X in combination with a 2 Gaussian, 1 region statistical model
      was capable of identifying the correct diastereomer among up to an upper limit of
      32 potential diastereomers. Overall a 2-fold reduction in structural uncertainty
      and a 7-fold reduction in model overconfidence have been achieved. Tools for
      rapid set-up and analysis of computational and experimental results, as well as
      for the statistical model generation, have been developed and are provided. All
      of this should facilitate rapid and reliable computational NMR structure
      elucidation, which has become a valuable tool to natural product chemists and
      synthetic chemists alike.

PMID- 29044274
TI  - Pd-Catalysed Suzuki coupling of alpha-bromoethenylphosphonates with
      organotrifluoroborates: a general protocol for the synthesis of terminal alpha
      substituted vinylphosphonates.
AB  - A general and robust protocol for the synthesis of terminal alpha-substituted
      vinylphosphonates via Suzuki coupling of alpha-bromovinylphosphonates with
      organotrifluoroborates has been successfully developed. This method features a
      broad substrate scope, great functional group compatibilities, and easy scale-up
      ability. In addition to easy access of nucleophiles, a straightforward synthesis
      of electrophiles was also realized with diethyl alpha-bromoethenylphosphonate as
      the starting material. With a combination of Pd2(dba)3/SPhos as the catalyst, a
      range of alpha-alkyl, aryl, heteroaryl, and alkynyl substituted
      ethenylphosphonates could be nicely accessed under mild conditions. As a
      synthetic application, the terminal vinylphosphonate was utilized as an effective
      Michael acceptor in the visible-light-promoted Giese reaction.

PMID- 29044277
TI  - Cationic phthalocyanine dendrimers as potential antimicrobial photosensitisers.
AB  - In the present study we describe the synthesis, photophysical properties and the
      photoinactivation performance against representative microorganisms of two
      families of cationic dendrimeric phthalocyanines as potential photosensitisers.
      Four charged dendrimeric compounds varying in their degree of ionicity (4 or 8
      positive charges) and the coordinating metal (zinc or ruthenium) are compared and
      assessed as potential photosensitising agents in terms of their antimicrobial
      activity.

PMID- 29044278
TI  - Enzymatic monoesterification of symmetric diols: restriction of molecular
      conformations influences selectivity.
AB  - We have experimentally demonstrated that by 'locking' the molecular conformation
      through the introduction of a double or triple bond in the center of a symmetric
      diol, enzymatic monoesterification can be achieved selectively. The enzyme
      Candida antarctica lipase B, generally used for the transesterification of diols,
      can be effectively used for the monoesterification of symmetrical diols in an
      unbuffered system also. By varying the chain length of a carboxylic acid moiety,
      we have established that optimum selectivity and efficiency can be achieved in
      the range of 4.8 to 5.0 pKa values. Selectivity can be improved up to 98.75% for
      a monoester in an overall 73% yield (mixture of a monoester and a diester) when
      but-2-yne-1,4-diol reacted with hexanoic acid. Water, a by-product, provides an
      interfacial environment for the enzyme to work in the organic reaction medium.
      The uniqueness of the reported monoesterification protocol is that it involves
      only the mechanical stirring of the reaction mixture at room temperature in the
      presence of the enzyme for 24 h. High percentage yield with selectivity for a
      monoester, easier product isolation and overall, environmental sustainability are
      added advantages. The synthesized monoesters are characterized by using HNMR and
      high resolution mass spectrometry (HRMS).

PMID- 29044284
TI  - Buckling patterns in biaxially pre-stretched bilayer shells: wrinkles, creases,
      folds and fracture-like ridges.
AB  - We introduce a new experimental system to study the effects of pre-stretch on the
      buckling patterns that emerge from the biaxial compression of elastomeric bilayer
      shells. Upon fabrication of the samples, releasing the pre-stretch in the
      substrate through deflation places the outer film in a state of biaxial
      compression and yields a variety of buckling patterns. We systematically explore
      the parameter space by varying the pre-stretch of the substrate and the ratio
      between the stiffness of the substrate and film. The phase diagram of the system
      exhibits a variety of buckling patterns: from the classic periodic wrinkle to
      creases, folds, and high aspect ratio ridges. Our system is capable of readily
      transitioning between these buckling patterns, a first for biaxial systems. We
      focus on the wrinkle to ridge transition. In the latter, we find that pre-stretch
      plays an essential role and that the ridge geometry (width, height) remains
      nearly constant throughout their formation process. For the localized ridged
      patterns, we find that the propagation of the ridge tip depends strongly on both
      strain and stiffness ratio, in a way that is akin to hierarchical fracture.

PMID- 29044289
TI  - Preoperative diagnostics in differentiated thyroid carcinoma.
AB  - AIM: The preoperative diagnosis of differentiated thyroid carcinomas (DTC) is
      particularly challenging in view of the high prevalence of thyroid nodules in the
      general population. Incidental diagnosis of DTC, on the other hand, can lead to
      reoperations and increased risk of morbidity. This study aimed to assess the
      prediction value of preoperative DTC dignity assessment and it's impact on
      surgical approaches. METHODS: We retrospectively reviewed 107 cases of DTC and
      subdivided them in three groups based on the preoperative dignity assessment:
      suspected malignancy (SM), unclear dignity (UD), and incidental findings (IF).
      The group differences were investigated in terms of diagnostic methods, findings,
      and impact on the subsequent surgical approach. RESULTS: The patient groups
      consisted of n = 51 (SM), n = 32 (UD), and n = 24 (IF). The tumor size, T
      staging, and ultrasound (US) assessment had the largest impact on the dignity
      classification (each p < 0.001). Scintigraphy was performed in 80 % of the
      patients, fine-needle aspiration cytology (FNAC) in 28 %. Hypofunction at
      scintigraphy (p < 0.001) and cytology results (p < 0.01) were identified as
      significant predictors for group assignment. Other significant factors were the
      frequency of the US documentation of nodule characteristics (p < 0.001) and
      malignancy criteria (p < 0.01) as well as reduced thyroid-stimulating hormone
      (TSH) levels (p < 0.01). Frozen section (p < 0.001) and total thyroidectomy (p <
      0.01) at initial surgery were performed significantly more often in the MV group.
      Reoperations were significantly more frequent in the IF group (p < 0.001).
      CONCLUSIONS: A relevant number of DTC cases was diagnosed incidentally, leading
      to significantly more frequent reoperations. A more systematic diagnostic
      approach with complete documentation of the findings according to current
      guidelines should be pursued.

PMID- 29044290
TI  - Protease-Activated Receptor PAR-4: An Inducible Switch between Thrombosis and
      Vascular Inflammation?
AB  - Thrombin triggers activation of platelets through protease-activated receptor 1
      (PAR-1) and PAR-4. Both receptors are widely expressed and exert multiple
      platelet-independent functions. PAR signalling contributes to healing responses
      after injury, by promoting cytokine activity and cellular growth and mobility.
      Uncontrolled PAR activation, however, can prevent timely resolution of
      inflammation, enhance thrombogenic endothelial function and drive adverse
      remodelling. The specific role of PAR-4 in thromboinflammatory vascular disease
      has been largely underestimated, given the relatively limited expression of PAR-4
      in non-platelet cells under healthy conditions. However, unlike PAR-1, PAR-4
      expression adapts dynamically to numerous stimuli associated with
      thromboinflammation, including thrombin, angiotensin II, sphingosine-1-phosphate
      (S1P), high glucose and redox stress, suggesting expression is switched on 'at
      need'. Prostacyclin negatively regulates PAR-4 expression at the post
      transcriptional level, which may serve to fine-tune thrombin responses and limit
      these to the injury site. PAR-4 elicits inflammatory, mitogenic and proliferative
      actions not only in response to thrombin but also to numerous other inflammatory
      proteases, and can cross-talk with other receptor systems such as S1P and
      adenosine receptors. Accordingly, PAR-4 has emerged as a candidate player in
      vessel disease and cardiac post-infarction remodelling. Currently, PAR-4 is a
      particularly promising target for safer anti-thrombotic therapies. Recent studies
      with the PAR-4 antagonist BMS-986120 lend support to the concept that selective
      antagonism of PAR-4 may offer both an effective and safe anti-thrombotic therapy
      in the acute thrombotic setting as well as an anti-inflammatory strategy to
      prevent long-term progressive atherosclerotic disease in high-risk cardiovascular
      patients.

PMID- 29044291
TI  - Preprocedural Leucocyte Count Predicts Risk in Patients with Coronary Chronic
      Total Occlusion.
AB  - Background As technologies of percutaneous coronary intervention (PCI) for
      coronary chronic total occlusions (CTO) have improved, great uncertainty exists
      regarding patient selection and long-term benefit of CTO-PCI. Given that white
      blood cell (WBC) count has been associated with cardiovascular risk, we
      hypothesized that the latter might provide incremental prognostic value in
      patients undergoing CTO-PCI. Methods and Results Our study population consisted
      of 1,262 consecutive patients (76.3% males, mean age of 67.7 +/- 10.3 years) who
      underwent elective PCI at our centre between January 2002 and December 2008. Four
      hundred seventy-five patients had at least one CTO, while 787 patients with non
      occlusive coronary lesions served as controls. Baseline WBC count was higher in
      CTO patients as compared with controls (8,072 +/- 3,459/MUL vs. 7,469 +/-
      2,668/MUL, p = 0.001) and independently predicted the occurrence of a CTO lesion
      (odds ratio: 1.8; 95% confidence interval [CI]: 1.3-2.4; p < 0.001). After a
      median follow-up of 3.1 years (interquartile range: 2.1-4.2 years), CTO patients
      with WBC counts ranging in the highest tertile had significantly worse outcomes
      than CTO patients with lower WBC counts (log-rank = 0.009 for all-cause mortality
      and log-rank = 0.01 for major adverse cardiac events). These associations were
      not seen in controls. Accordingly, elevated WBC count was identified as a
      significant predictor for all-cause mortality (adjusted hazard ratio: 3.1; 95%
      CI: 1.6-6.2; p = 0.001) in CTO patients but not in patients with non-occlusive
      coronary artery disease (pint = 0.088). Conclusion Assessment of the inflammatory
      status of CTO patients may be an important element in selecting CTO patients at
      low risk who may be referred to CTO-PCI.

PMID- 29044292
TI  - Investigation of the Filamin A-Dependent Mechanisms of Tissue Factor
      Incorporation into Microvesicles.
AB  - We have previously shown that phosphorylation of tissue factor (TF) at Ser253
      increases the incorporation of TF into microvesicles (MVs) following protease
      activated receptor 2 (PAR2) activation through a process involving filamin A,
      whereas phosphorylation of TF at Ser258 suppresses this process. Here, we
      examined the contribution of the individual phosphorylation of these serine
      residues to the interaction between filamin A and TF, and further examined how
      filamin A regulates the incorporation of TF into MVs. In vitro binding assays
      using recombinant filamin A C-terminal repeats 22-24 with biotinylated phospho-TF
      cytoplasmic domain peptides as bait showed that filamin A had the highest binding
      affinities for phospho-Ser253 and double-phosphorylated TF peptides, while the
      phospho-Ser258 TF peptide had the lowest affinity. Analysis of MDA-MB-231 cells
      using an in situ proximity ligation assay revealed increased proximity between
      the C-terminus of filamin A and TF following PAR2 activation, which was
      concurrent with Ser253 phosphorylation and TF-positive MV release from these
      cells. Knock-down of filamin A expression suppressed PAR2-mediated increases in
      cell surface TF procoagulant activity without reducing cell surface TF antigen
      expression. Disrupting lipid rafts by pre-incubation with methyl-beta
      cyclodextrin prior to PAR2 activation reduced TF-positive MV release and cell
      surface TF procoagulant activity to the same extent as filamin A knock-down. In
      conclusion, this study shows that the interaction between TF and filamin A is
      dependent on the differential phosphorylation of Ser253 and Ser258. Furthermore,
      the interaction of TF with filamin A may translocate cell surface TF to
      cholesterol-rich lipid rafts, increasing cell surface TF activity as well as TF
      incorporation and release into MVs.

PMID- 29044293
TI  - Down Regulation of the Munc18b-syntaxin-11 Complex and beta1-tubulin Impairs
      Secretion and Spreading in Neonatal Platelets.
AB  - Neonatal platelets are hyporeactive and show impaired agonist-induced secretion
      despite no obvious abnormalities in their granules. Here, we examined, for the
      first time, the ultrastructure of neonatal and adult platelets following agonist
      activation. Under resting conditions, neonatal and adult platelets appeared
      ultrastructurally identical. Following agonist stimulation, however, noticeable
      degranulation occurred in adult platelets, while granules in neonatal platelets
      remained clearly visible and apparently unable to centralize or fuse. To
      investigate the underlying mechanisms, we first examined the expression levels of
      the main SNARE proteins, which mediate the membrane fusion events required for
      exocytosis. Neonatal platelets showed significantly reduced levels of syntaxin-11
      and its regulator, Munc18b. Since granule centralization depends on contraction
      of the microtubule ring, we also examined the expression of its main component,
      beta1-tubulin. Noteworthy, we found decreased TUBB1 mRNA and protein levels in
      neonatal platelets, while TUBB2A and TUBB isoforms were overexpressed, partially
      compensating for that deficiency. Finally, supporting the functional consequences
      of defective exocytosis, adhesion kinetic assays, performed in plasma-free
      medium, demonstrated delayed adhesion and spreading of neonatal platelets. This
      is the first report showing marked reductions of syntaxin-11-Munc18b complex and
      beta1-tubulin in neonatal platelets, indicating that these proteins, required for
      platelet degranulation, are developmentally regulated.

PMID- 29044294
TI  - Serum Levels of Anti-PON1 and Anti-HDL Antibodies as Potential Biomarkers of
      Premature Atherosclerosis in Systemic Lupus Erythematosus.
AB  - The present study aimed to evaluate the possible role of immunoglobulin G (IgG)
      antibodies against high-density lipoproteins (HDL) and paraoxonase 1 (PON1) as
      possible biomarkers of cardiovascular disease (CVD) in systemic lupus
      erythematosus (SLE). To this end, levels of these autoantibodies, PON1 activity
      and total antioxidant capacity were quantified in serum samples from 198 SLE
      patients, 100 healthy controls (HC) and 42 non-autoimmune individuals with
      traditional cardiovascular risk factors. PON1 rs662 polymorphism was analysed in
      a subgroup of patients and controls. Subclinical CVD were determined by Doppler
      ultrasound in 118 SLE patients and 30 HC, analysing carotid intima-media
      thickness (IMT) and blood flow parameters in internal carotid, middle cerebral
      and basilar arteries. Serum levels of both anti-HDL and anti-PON1 antibodies were
      increased in SLE patients compared with HC (p < 0.001); however, only anti-PON1
      antibodies, in addition to disease activity, were significant predictors of the
      impaired PON1 function in SLE (beta  = -0.143, p = 0.045). Conversely, anti-HDL
      antibodies were associated with higher risk of CVD (odds ratio: 3.69; p = 0.012)
      and lower HDL levels at disease onset (rho = -0.324, p = 0.044). Finally, anti
      PON1 antibodies were associated with carotid IMT in SLE (beta = 0.201, p = 0.008)
      and inversely related to cranial arteries blood flow velocities in patients with
      clinical and subclinical CVD (all p < 0.001). In sum, these findings allowed us
      to propose serum levels of anti-PON1 and anti-HDL antibodies as potential early
      biomarkers of endothelial damage and premature atherosclerosis in SLE, thus
      constituting useful therapeutic targets for the prevention of future CVD in these
      patients.

PMID- 29044295
TI  - Clinical Decision Rules for Pulmonary Embolism in Hospitalized Patients: A
      Systematic Literature Review and Meta-analysis.
AB  - Background Clinical decision rules (CDRs) for pulmonary embolism (PE) have been
      validated in outpatients, but their performance in hospitalized patients is not
      well characterized. Objectives The goal of this systematic literature review was
      to assess the performance of CDRs for PE in hospitalized patients. Methods We
      performed a structured literature search using Medline, EMBASE and the Cochrane
      library for articles published on or before January 18, 2017. Two authors
      reviewed all titles, abstracts and full texts. We selected prospective studies of
      symptomatic hospitalized patients in which a CDR was used to estimate the
      likelihood of PE. The diagnosis of PE had to be confirmed using an accepted
      reference standard. Data on hospitalized patients were solicited from authors of
      studies in mixed populations of outpatients and hospitalized patients. Study
      characteristics, PE prevalence and CDR performance were extracted. The
      methodological quality of the studies was assessed using the QUADAS instrument.
      Results Twelve studies encompassing 3,942 hospitalized patients were included.
      Studies varied in methodology (randomized controlled trials and observational
      studies) and reference standards used. The pooled sensitivity of the modified
      Wells rule (cut-off <= 4) in hospitalized patients was 72.1% (95% confidence
      interval [CI], 63.7-79.2) and the pooled specificity was 62.2% (95% CI, 52.6
      70.9). The modified Wells rule (cut-off <= 4) plus D-dimer testing had a pooled
      sensitivity 99.7% (95% CI, 96.7-100) and pooled specificity 10.8% (95% CI, 6.7
      16.9). The efficiency (proportion of patients stratified into the 'PE unlikely'
      group) was 8.4% (95% CI, 4.1-16.5), and the failure rate (proportion of low
      likelihood patients who were diagnosed with PE during follow-up) was 0.1% (95%
      CI, 0-5.3). Conclusion In symptomatic hospitalized patients, use of the Wells
      rule plus D-dimer to rule out PE is safe, but allows very few patients to forgo
      imaging.

PMID- 29044296
TI  - Mitochondria and Platelet Cell Death.

PMID- 29044297
TI  - PSA levels, PSA doubling time, Gleason score and prior therapy cannot predict
      measured uptake of [68Ga]PSMA-HBED-CC lesion uptake in recurrent/metastatic
      prostate cancer.
AB  - AIM: To assess whether clinical prostate cancer (PCA) related factors and therapy
      status can predict the degree of tracer uptake on [68Ga]PSMA-HBED-CC PET/CT.
      MATERIALS & METHODS: We retrospectively studied 124 patients with recurrent an/or
      metastatic PCA who underwent [68Ga]PSMAHBED-CC PET/CT. The maximum standardized
      uptake value (SUVmax) was determined in the prostate bed as well as in three size
      categories (<= 5 mm, > 5-15 mm, > 15 mm) in pelvic lymph node, extrapelvic lymph
      node, bone and visceral metastases. RESULTS: Significant positive correlations
      between lesion size and SUVmax were found in pelvic lymph node metastases > 5 
      <=15 mm (Spearmans rho = 0.502, p = 0.002) as well as in extrapelvic lymph node
      metastases5 mm (rho = 0.314, p = 0.033) and > 5 <=-15 mm (rho = 0.614, p <
      0.001). SUVmax tended to be higher in the largest diameter category in each
      anatomic station than in the middle and lower categories. We were unable to find
      evidence for a relationship between SUVmax and PSA, PSAdt, Gleason score,
      androgen deprivation therapy, radiation therapy or chemotherapy status.
      CONCLUSION: Measured tracer uptake in [68Ga]PSMA-HBED-CC PET/CT in patients with
      recurrent/metastasized prostate cancer is significantly influenced by lesion size
      as a result of partial volume effects in the very small lesions. Clinical
      indicators of aggressive prostate cancer behaviour such as PSA levels, PSA
      doubling time or the Gleason score of the primary tumour, as well as the androgen
      deprivation therapy, radiation therapy or chemotherapy status are not related to
      measured tracer uptake. ZIEL:: Beantwortung der Frage ob klinisch bestimmbare
      Faktoren und Therapiestatus bei Prostatakarzinom (PCA) eine Vorhersage zur
      Traceranreicherung in [68Ga]PSMA-HBED-CC PET/CT liefern konnen.Material &
      Methoden: 124 Patienten mit rezidiviertem und/oder metastasiertem PCA die
      [68Ga]PSMA-HBED-CC PET/CT untergingen, wurden retrospektiv untersucht. Der
      maximum Standardized Uptake Value (SUVmax) wurde in der Prostataloge gemessen
      sowie in drei Grobetaen-Kategorien ( 5 mm, > 5-15 mm, > 15 mm) in Metastasen in
      den pelvinen Lymphknoten-, extrapelvinen Lymphknoten-, Knochen- und viszeralen
      Metastasen. ERGEBNISSE: Signifikant positive Korrelationen zwischen
      Lasionsgrobetae und SUVmax wurden in pelvinen Lymphknotenmetastasen > 5 -<=15 mm
      (Spearmans rho = 0.502, p = 0.002), extrapelvinen Lymphknotenmetastasen5 mm (rho
      = 0.314, p = 0.033) und > 5 -<=15 mm (rho = 0.614, p < 0.001) gefunden. Fur jede
      anatomische Lokalisation wurde ein hoherer Wert SUVmax innerhalb der grobetaten
      Kategorie verglichen zu mittleren und kleinsten Kategorie gefunden.

PMID- 29044298
TI  - The Performance of CRUSADE and ACUITY Bleeding Risk Scores in Ticagrelor-Treated
      ACS Patients Who Underwent PCI.
AB  - The performance of the CRUSADE (Can Rapid risk stratification of Unstable angina
      patients Suppress ADverse outcomes with Early implementation of the ACC/AHA
      guidelines) and ACUITY (Acute Catheterization and Urgent Intervention Triage
      strategy) risk scores for the prediction of major bleeding in ticagrelor-treated
      acute coronary syndrome (ACS) patients who underwent percutaneous coronary
      intervention (PCI) is unknown. The aim of the present study is to validate the
      performance of both scores in a contemporary Chinese cohort of ACS patients
      hospitalized for PCI and administrated with ticagrelor. From January 2013 to
      December 2014, a total of 629 ticagrelor-treated ACS patients who underwent PCI
      were recruited consecutively. The overall rate of major bleeding defined by the
      BARC (Bleeding Academic Research Consortium) criteria was 1.7%. This incidence
      increased with the risk category of both the CRUSADE (very low, 0.6%; low, 1.3%;
      moderate, 1.1%; high, 7.0%; and very high, 13.0%; p = 0.001) and the ACUITY score
      (low, 0.6%; moderate, 1.4%; high, 4.9%; and very high, 7.0%; p = 0.003). The
      CRUSADE score demonstrated adequate calibration and discriminatory capacity for
      the patients as a whole (HL-p [Hosmer-Lemeshow goodness-of-fit test p-value]
      >0.3; AUC [area under the curve]: 0.78), with the excellent performance in the
      subgroups of acute myocardial infarction, men, diabetes and those implanted with
      more than two DESs (AUC: 0.85, 0.80, 0.93 and 0.93, respectively). For the ACUITY
      score, adequate calibration and discriminatory capacity could be observed for the
      whole patients (HL-p > 0.3; AUC: 0.78), with excellent performance for the
      patients with diabetes or those implanted with more than two DESs (AUC: 0.90 and
      0.97, respectively). In conclusion, both CRUSADE and ACUITY risk scores performed
      adequate discriminatory power for the prediction of major bleeding within 30 days
      in ticagrelor-treated ACS patients who underwent PCI.

PMID- 29044299
TI  - Erratum: Brazilian guidelines for the clinical management of
      paracoccidioidomycosis.
AB  - [This corrects the article doi: 10.1590/0037-8682-0230-2017].

PMID- 29044301
TI  - Is APACHE II a useful tool for clinical research?

PMID- 29044302
TI  - Functional ability in younger and older elderlies after discharge from the
      intensive care unit. A prospective cohort.
AB  - OBJECTIVE: To compare the functional capacity of younger elderly individuals (60
      to 79 years old) with that of older elderly individuals (>= 80 years old) during
      the first 6 months after discharge from the intensive care unit. METHODS: A
      multicenter prospective cohort study was conducted, in which data on intensive
      care unit admission and outcomes after hospital discharge (immediate post
      discharge, after 3 months and after 6 months) were collected. Muscle strength was
      evaluated through the protocol of the Medical Research Council and dynamometry
      (handgrip); the ability to perform activities of daily life and functional
      independence were assessed by the Barthel index and the usual level of physical
      activity (International Physical Activity Questionnaire); and quality of life was
      assessed by the 12-Item Short-Form Health Survey Version 2. RESULTS: Among the
      253 patients included, 167 were younger elderly (between 61 and 79 years old),
      and 86 were older elderly (>= 80 years old). During the sixth month of
      evaluation, the older elderlies presented a higher need for a caregiver (69.0%
      versus 49, 5%, p = 0.002). Functional capacity prior to intensive care unit
      admission and in the third month after discharge was lower in older elderlies
      than in younger ones (Barthel prior to the intensive care unit: 73.0 +/- 30.0
      versus 86.5 +/- 22.6; p <0.001, Barthel in the third month: 63.5 +/- 34.0 versus
      71.5 +/- 35.5, p = 0.03), as was the usual level of physical activity
      (International Physical Activity Questionnaire in the third month: active/very
      active 3.4% versus 18.3%, no physical activity 64.4% versus 39.7%, p < 0.001, and
      International Physical Activity Questionnaire in the sixth month: active/very
      active 5.8% versus 20.8%, no physical activity 69.2% versus 43.4%, p = 0.005).
      Older elderlies had lower muscle strength when assessed according to handgrip in
      both the dominant (14.5 +/- 7.7 versus 19.9 +/- 9.6, p = 0.008) and non-dominant
      limb (13.1 +/- 6.7 versus 17.5 +/- 9.1, p = 0.02). There were no differences in
      functional capacity loss or reported quality of life between the age groups.
      CONCLUSION: Although there were great functional capacity losses after discharge
      from the intensive care unit in both age groups, there was no difference in the
      magnitude of functional capacity loss between younger (60 to 79 years) and older
      elderly individuals (>= 80 years old) during the first 6 months after discharge
      from the intensive care unit.

PMID- 29044303
TI  - Immediate postoperative of bariatric surgery in the intensive care unit versus an
      inpatient unit. A retrospective study with 828 patients.
AB  - OBJECTIVE: To compare the incidence of complications and the duration of
      hospitalization of patients undergoing bariatric surgery admitted to the
      intensive care unit or a post-surgical hospitalization unit. METHODS: This
      retrospective observational study included 828 patients admitted between January
      2010 and February 2015 during the immediate postoperative period of bariatric
      surgery in a hospital. Data were collected via electronic medical records. The
      Mann-Whitney test was used to compare continuous variables, and the chi-square
      was used to compare categorical variables. RESULTS: Patients in both groups had
      similar demographic characteristics, with no significant differences in
      anthropometric data and comorbidities. There was no significant difference in the
      comparison of complications between the two groups. However, the group admitted
      to the intensive care unit had longer hospitalization times (median of 3 days
      versus 2 days, p < 0.05), and hospital costs were 8% higher. CONCLUSION: The
      present study found no benefit in the routine admittance of patients to the
      intensive care unit after undergoing bariatric surgery. This practice increased
      hospitalization time and hospital costs, which wasted resources. It is necessary
      to create objective criteria to identify patients requiring intensive care unit
      admission after bariatric surgery.

PMID- 29044304
TI  - Delirium in a Latin American intensive care unit. A prospective cohort study of
      mechanically ventilated patients.
AB  - OBJECTIVE: To establish the prevalence of delirium in a general intensive care
      unit and to identify associated factors, clinical expression and the influence on
      outcomes. METHODS: This was a prospective cohort study in a medical surgical
      intensive care unit. The Richmond Agitation-Sedation Scale and Confusion
      Assessment Method for the Intensive Care Unit were used daily to identify
      delirium in mechanically ventilated patients. RESULTS: In this series, delirium
      prevalence was 80% (N = 184 delirious patients out of 230 patients). The number
      of patients according to delirium psychomotor subtypes was as follows: 11
      hyperactive patients (6%), 9 hypoactive patients (5%) and 160 mixed patients
      (89%). Multiple logistic regression modeling using delirium as the dependent
      outcome variable (to study the risk factors for delirium) revealed that age > 65
      years, history of alcohol consumption, and number of mechanical ventilation days
      were independent variables associated with the development of delirium. The
      multiple logistic regression model using hospital mortality as the dependent
      outcome variable (to study the risk factors for death) showed that severity of
      illness, according to the Acute Physiology and Chronic Health Evaluation II,
      mechanical ventilation for more than 7 days, and sedation days were all
      independent predictors for excess hospital mortality. CONCLUSION: This Latin
      American prospective cohort investigation confirmed specific factors important
      for the development of delirium and the outcome of death among general intensive
      care unit patients. In both analyses, we found that the duration of mechanical
      ventilation was a predictor of untoward outcomes.

PMID- 29044305
TI  - Dysglycemia in the critically ill patient: current evidence and future
      perspectives.
AB  - Dysglycemia in critically ill patients (hyperglycemia, hypoglycemia, glycemic
      variability and time in range) is a biomarker of disease severity and is
      associated with higher mortality. However, this impact appears to be weakened in
      patients with previous diabetes mellitus, particularly in those with poor
      premorbid glycemic control; this phenomenon has been called "diabetes paradox".
      This phenomenon determines that glycated hemoglobin (HbA1c) values should be
      considered in choosing glycemic control protocols on admission to an intensive
      care unit and that patients' target blood glucose ranges should be adjusted
      according to their HbA1c values. Therefore, HbA1c emerges as a simple tool that
      allows information that has therapeutic utility and prognostic value to be
      obtained in the intensive care unit.

PMID- 29044307
TI  - Immune reconstitution inflammatory syndrome as a cause of autoimmune hepatitis
      and acute liver failure.
AB  - Acute liver failure is a rare syndrome with high mortality and is often diagnosed
      late. Intensivist physicians play fundamental roles in the diagnostic suspicion
      and the management of the multiple-organic dysfunctions characteristic of this
      entity. Immune reconstitution inflammatory syndrome is an entity that is
      characterized by the paradoxical worsening of the patient's previous condition,
      after the initiation of antiretrovirals, triggered against either pathogens
      present in the host or autoantigens. Autoimmune hepatitis has recently been
      described as one of these autoimmune manifestations. The authors report the first
      case with evolution to acute liver failure and death within a few days after the
      development of encephalopathy, review the cases of autoimmune hepatitis described
      and comment on the therapeutic possibilities in this context.

PMID- 29044306
TI  - Biomarkers of renal recovery after acute kidney injury.
AB  - Novel biomarkers can be suitable for early acute kidney injury diagnosis and the
      prediction of the need for dialysis. It remains unclear whether such biomarkers
      may also play a role in the prediction of recovery after established acute kidney
      injury or in aiding the decision of when to stop renal support therapy. PubMed,
      Web of Science and Google Scholar were searched for studies that reported on the
      epidemiology of renal recovery after acute kidney injury, the risk factors of
      recovery versus non-recovery after acute kidney injury, and potential biomarkers
      of acute kidney injury recovery. The reference lists of these articles and
      relevant review articles were also reviewed. Final references were selected for
      inclusion in the review based on their relevance. New biomarkers exhibited a
      potential role in the early diagnosis of acute kidney injury recovery. Urine HGF,
      IGFBP-7, TIMP-2 and NGAL may improve our ability to predict the odds and timing
      of recovery and eventually renal support withdrawal. Acute kidney injury recovery
      requires more study, and its definition needs to be standardized to allow for
      better and more powerful research on biomarkers because some of them show
      potential for the prediction of acute kidney injury recovery.

PMID- 29044308
TI  - Heart conduction system defects and sustained ventricular tachycardia
      complications in a patient with granulomatosis with polyangiitis. A case report
      and literature review.
AB  - Granulomatosis with polyangiitis is a rare systemic inflammatory disorder
      characterized by vasculitis of the small arteries, the arterioles and the
      capillaries together with necrotizing granulomatous lesions. This case reports on
      a young female patient, previously diagnosed with granulomatosis with
      polyangiitis, who was admitted to the intensive care unit with seizures and
      hemodynamic instability due to a complete atrioventricular heart block. The event
      was associated with multiple episodes of sustained ventricular tachycardia
      without any structural heart changes or electrolyte disturbances. In the
      intensive care unit, the patient was fitted with a provisory pacemaker, followed
      by immunosuppression with corticosteroids and immunobiological therapy, resulting
      in a total hemodynamic improvement. Severe conduction disorders in patients
      presenting granulomatosis with polyangiitis are rare but can contribute to
      increased morbidity. Early detection and specific intervention can prevent
      unfavorable outcomes, specifically in the intensive care unit.

PMID- 29044309
TI  - Influence of dentistry professionals and oral health assistance protocols on
      intensive care unit nursing staff. A survey study.

PMID- 29044300
TI  - 3rd Guideline for Perioperative Cardiovascular Evaluation of the Brazilian
      Society of Cardiology.

PMID- 29044311
TI  - Accidental breakage of needle during subclavian vein catheterization: an
      adversity uncalled for!

PMID- 29044310
TI  - Oral histoplasmosis.

PMID- 29044312
TI  - Effect of carbon source on production, characterization and bioactivity of
      exopolysaccharide produced by Phellinus vaninii Ljup.
AB  - The effect on different three carbon source (i.e. glucose, fructose and sucrose)
      on production, chemical characterization and antioxidant activity of
      exopolysaccharide (EPS) produced by Phellinus vaninii Ljup was investigated in
      this study. Amongst carbon sources examined, glucose and sucrose were favorable
      for the mycelia growth, while the maximum EPS yield was achieved when sucrose was
      employed. The predominant carbohydrate compositions in EPSs identified were
      gluconic acid, glucose, mannose and galactose acid. Then, FT-IR spectral analysis
      revealed prominent characteristic groups in EPSs. EPSs molecule exist as nearly
      globular shape form in aqueous solution. The variation also affects antioxidant
      activities by investigated by using hydroxyl and DPPH radical scavenging assay.
      Sucrose was best carbon source from the viewpoint of antioxidant activity due to
      the relatively high contents of galactose in the EPS with moderate molecular
      weight and polydispersity.

PMID- 29044313
TI  - Evaluation of the anti-osteoporotic effect of Ginkgo biloba L. in Wistar rats
      with glucocorticoid-induced-osteoporosis by bone densitometry using dual-energy x
      ray absorptiometry (DEXA) and mechanical testing.
AB  - Evaluate the effect of the extract of Ginkgo biloba in the bone alkaline
      phosphatase, bone mineral density, in the mechanical properties of the tibia in
      rats with glucocorticoid-induced-osteoporosis. After osteoporosis induction, the
      rats were divided into five groups: Osteoporosis; EGb1 (28 mg/Kg); EGb2 (56
      mg/Kg); alendronate (0.2 mg/animal) and control. The animals were treated during
      20 and 30 days. The control group was compared with the osteoporosis's (Student's
      t-test), while the other were analyzed by ANOVA test followed by Tukey/Dunnett'T3
      (p<0.05). In the osteoporosis group the bone alkaline phosphatase, bone mineral
      density, the bone stiffness, the maximum load and the resilience were reduced.
      The bone alkaline phosphatase values increased in the EGb1 and EGb2 groups (30
      days). In addition, in the EGb2 and alendronate groups (20 and 30 days) the bone
      mineral density increased. The extract of Ginkgo biloba restored bone alkaline
      phosphatase and bone mineral density using dual-energy x-ray absorptiometry.

PMID- 29044314
TI  - Diversity of parasites in wild Astronotus ocellatus (Perciformes, Cichlidae), an
      ornamental and food fish in Brazil.
AB  - The community composition of parasites was characterized in Astronotus ocellatus
      from a tributary of the Amazon River, northern Brazil. The prevalence was 87.9%,
      and a total of 526,052 parasites were collected, with a mean of 15,941 parasites
      per host. Nine taxa of ecto- and endo-parasites were identified, but
      Ichthyophthirius multifiliis was the dominant species, while Piscinoodinium
      pillulare, Clinostomum marginatum and Argulus multicolor were the least prevalent
      parasites. The parasite community was characterized by a low species richness,
      low diversity and low evenness. Host body size was not found to influence the
      composition of the parasite community, and there was no significant correlation
      between abundance of any parasite species and host body size. Papers published
      concerning the presence of parasites in this host in different hydrographic
      basins within Brazil indicate that 22 species of parasites are known to infect A.
      ocellatus, including species of ectoparasites and endoparasites. In Brazil,
      ectoparasites species, particularly crustaceans, have been found to parasitize A.
      ocellatus in relatively high numbers. This predominance of ectoparasites is
      typical of fish of lentic ecosystems. Finally, the presence of different
      endoparasites taxa suggest that A. ocellatus acts as an intermediate or
      definitive host.

PMID- 29044315
TI  - Implementation of dental specialty centers: a descriptive analysis of the current
      status in the Brazilian territory.
AB  - This study aimed to assess the current implementation status of Dental Specialty
      Centers (Centros de Especialidades Odontologicas - CEO) in Brazil. The sample
      included CEOs implemented up to November 2015 in the 27 Brazilian federative
      units. Data were obtained directly from the database of the Informatics
      Department of the Brazilian Unified Health System, according to the National
      Registry of Health Facilities (NRHF) of Dental Specialty Centers of all Brazilian
      regions. Primary care data were also collected from the cities with implemented
      CEOs, including coverage status of the Family Health Strategy (FHS) and number of
      Oral Health Teams (OHT) I and II, at 2 collection periods (January 2006 and
      November 2015). There were 1019 CEOs implemented in Brazil, which were unequally
      distributed among the Brazilian states, with prevalence of implementation of CEOs
      type II (n=503, 49.4%). The statistical analysis showed significant difference
      between the three types of CEO (I, II, and III) and the variables of coverage
      rate (FHS) and number of teams (OHT I, OHT II) at both data collection periods.
      Although presenting an evolutionary aspect in the implementation of CEOs, the
      implementation of medium-complexity care in Brazil is disorganized.

PMID- 29044316
TI  - Species richness and composition of epiphytic bryophytes in flooded forests of
      Caxiuana National Forest, Eastern Amazon, Brazil.
AB  - This study aimed to compare the richness and composition of the epiphytic
      bryoflora between varzea and igapo forests in Caxiuana National Forest, Brazilian
      Amazon. Bryophytes were collected on 502 phorophytes of Virola surinamensis.
      Average richness per phorophyte and composition between forests and between dry
      and rainy periods was tested by two-way analysis and by cluster analysis,
      respectively. In total, 54 species of 13 families were identified. Richness was
      greater in igapo forest (44 species) compared to varzea forest (38 species).
      There was no significant difference in the number of species between the studied
      periods. Cluster analysis showed the bryoflora composition was different between
      varzea and igapo, but not between dry and rainy periods. Results did not
      corroborate the hypothesis that varzea forests harbor higher species richness
      than igapo forests.

PMID- 29044317
TI  - Potassium adsorption in soil cultivated with sugarcane.
AB  - Vinasse is a byproduct of the process of distillation of sugarcane juice for the
      manufacture of sugar and alcohol. Because it is rich in nutrients, mainly
      potassium (K), is used as fertilizer and applied via fertigation, without
      concerning for the fate of this compound in the soil. Thus, the objective of the
      study was to evaluate the interactions of the potassium ion (K+), applied via
      vinasse in a soil representative of the sugarcane zone of the State of Pernambuco
      using adsorption isotherms. The methodology was based on physical, chemical and
      soil mineralogical characterization, as well as equilibrium batch tests, where
      the experimental curves were fitted by Langmuir and Freundlich isotherm models.
      The results allowed to infer that the Freundlich model showed better fit of the
      curve in both forms: linear and non-linear (direct fit); the non-linear model was
      selected due to the values of coefficient of determination (R2). The interaction
      between potassium and soil occurred mainly with organic matter and the presence
      of soil kaolinite, because they showed negative ions on the external surface,
      thereby promoting potassium adsorption. Soil potassium adsorption capacity was
      higher for the first layer (0-20 cm) and decreased along the depth profile.

PMID- 29044318
TI  - Antibiotic activity of Plectranthus ornatus Codd., a Traditional Medicinal Plant.
AB  - The dichloromethane extract of Plectranthus ornatus Codd., a tradicional
      medicinal plant, showed antibiotic activity with minimum inhibitory concentration
      (MIC) values of 0.4 mg.mL-1 and 100 percent of biofilm inhibition against
      Staphylococcus aureus strains isolated from animals with mastitis infections.
      Based on these antibacterial activities, in addition to ethnopharmacological
      reports from healing men and farmers in Brazil, an herbal soap was produced from
      this active extract and was tested both in vitro and in vivo. In vivo assays
      conducted on these herbal soaps led to results similar to those previously
      conducted with the active extract. These results indicated the great potential of
      this plant for use as an excipient by preparing herbal antibacterial soaps as an
      alternative veterinary medicine aimed at controlling bovine mastitis infections
      on small Brazilian farms.

PMID- 29044319
TI  - Minimum free energy predicted base pairing in the 39 nt spliced leader and 5' UTR
      of calmodulin mRNA from Trypanosoma cruzi: influence of the multiple trans
      splicing sites.
AB  - We analyzed the compositional changes and the stable base pairs in the predicted
      secondary structure of the 5' UTR calmodulin mRNA in T. cruzi. The three copies
      of calmodulin in T. cruzi genome display variable position of the trans splicing
      sites and give rise to several mRNA that differs slightly on 5' UTR composition
      in the epimastigote stage. We show that the pattern of high probability base
      pairs in the minimum free energy predicted secondary structures of the calmodulin
      5' UTR remains unchanged despite the nucleotide composition variation. However,
      the 39 nt spliced leader (mini-exon, the 5' exon sequence transferred to
      trypanosome mRNAs by the mechanism of trans splicing) shows a variable pattern of
      high and low probability base pairing as consequence of the altered composition
      of the 5' UTR.

PMID- 29044320
TI  - Drought monitoring in the Brazilian Semiarid region.
AB  - Drought is a natural and recurrent phenomenon. It is considered 'a natural
      disaster' whenever it occurs in an intensive manner in highly populated regions,
      resulting in significant damage (material and human) and loss (socioeconomic).
      This paper presents the efforts developed to monitor the impact of drought in the
      semiarid region of Northeast Brazil. In this scope, information from different
      sources is compiled to support the evaluation and identification of impacted
      municipalities, with the main objective of supporting emergency actions to
      mitigate their impact. In the semiarid region of Brazil there are frequent
      occurrences of dry periods during the rainy season, which, depending on the
      intensity and duration, can cause significant damage to family-farmed crops, with
      a farming system characterized by low productivity indices. However, rain-fed
      agriculture has great economic expression and high social importance due to the
      region is densely occupied, and contributes to the establishment of communities
      in the countryside. Specifically, in the present study, the methodology adopted
      to monitor the impact of agricultural droughts, including an analysis of the
      hydrological year 2015-2016, is presented, considering different water stress
      indicators for the identification of the affected municipalities and assessment
      of the methods and tools developed.

PMID- 29044321
TI  - Comparative pollen morphological analysis in the subgenera Passiflora and
      Decaloba.
AB  - The genus Passiflora is the most diversified of the Passifloraceae, and its
      palynology presents wide morphological variability. The objective of the study
      was to evaluate the pollen morphology of 18 Passiflora species in order to
      identify informative pollinic characteristics to contribute to the taxonomic
      classification of the genus. The morphology of the pollen grains and the exine
      structure were investigated using light microscopy and scanning electron
      microscopy. Differences in the pollen morphology were found in the studied
      species, mainly in terms of shape, pollen aperture and ornamentation pattern of
      the exine. Most of the species belonging to the subgenus Passiflora presented
      ornamented 6-syncolpate pollen grains with an oblate-spheroidal shape and an
      exine with large lumens. In the subgenus Decaloba the pollen grains were 6
      colporate, 12-colpate and 12-colporate, with subprolate to prolate-spheroidal
      shape, as well as an exine with smaller lumen size and few ornamented. The pollen
      morphology of the species of the subgenera Passiflora and Decaloba has shown
      palynological characteristics that have specific diagnostic value, thus allowing
      a better understanding of the taxonomy of the genus Passiflora.

PMID- 29044322
TI  - Two new species and updated checklist of Oxyethira Eaton, 1873 (Trichoptera,
      Hydroptilidae) from Brazil.
AB  - Two new species of Oxyethira Eaton, 1873 are described: Oxyethira cascadanta sp.
      n. and Oxyethira quadrilobata sp. n. Description and illustrations of the new
      species are provided based on specimens collected in Parque Nacional da Serra da
      Canastra, Minas Gerais State, Southeast Brazil. Both species are assigned to the
      subgenus Loxotrichia but differ from other species mainly in morphology of the
      subgenital plate, subgenital processes and inferior appendages. Additionally, we
      provide an updated checklist of the Oxyethira species from Brazil.

PMID- 29044323
TI  - Mini-incubators improve the adventitious rooting performance of Corymbia and
      Eucalyptus microcuttings according to the environment in which they are
      conditioned.
AB  - We addressed a major challenge in the in vitro clonal propagation of Corymbia
      citriodora, Eucalyptus urophylla and E. benthamii by using an ex vitro
      adventitious rooting strategy in a mini-incubator. Mini-incubators were placed in
      four environments for rooting. A shade house with no fogging system and a
      greenhouse with no ventilation but with a fogging environment had the best
      performance in terms of rooting, root growth and survival of microcuttings. Daily
      recording of the temperature within each mini-incubator in each environment
      allowed the verification of negative correlations between the maximum average
      temperature and the survival, adventitious rooting and root growth. The ideal
      maximum air temperature for the efficient production of clonal plants was 28.4
      degrees C (+/- 5.5 degrees C), and the minimum was 20.3 degrees C (+/- 6.2
      degrees C). E. benthamii was more sensitive to higher temperatures than C.
      citriodora and E. urophylla. Nevertheless, placing mini-incubators in the shade
      house with no fogging system resulted in a stable and uniform performance among
      the three species, with 100.0% survival and 81.4% rooting. Histological sections
      of the adventitious roots revealed connection with the stem vascular cambium.
      Therefore, our experimental system demonstrated the potential of mini-incubators
      coupled with the proper environment to optimize the adventitious rooting
      performance of microcuttings.

PMID- 29044324
TI  - Replacing soybean oil with increasing levels of soybean acid oil in diets of
      coturnix quails (Coturnix coturnix coturnix) and the effects on egg quality.
AB  - The effects of increasing levels of soybean acid oil in diets of quails on the
      quality of eggs were evaluated over a period of 56 days. A completely randomized
      design with five treatment levels of soybean acid oil (0, 2, 4, 6, and 8%) as a
      replacer for soybean oil and eight replicates of two quails each were used. A
      total of 240 fresh eggs were used for quality analysis, and 400 eggs were stored
      at 23oC over a period of 0, 7, 14, 21, and 28 days for analysis of shelf-life.
      Polynomial regression and ANOVA with repeated measurements and Tukey's tests were
      used. Soybean acid oil linearly increased the intensity of red (a* = -5.26 + 0.14
      x, R2 = 0.89, P = 0.01) and yellow (b* = 42.32 + 0.44 x, R2 = 0.88 P = 0.01). All
      other variables of egg quality were not affected by the treatments, with the
      exception of sensory attributes, such as odor and aftertaste, which were more
      pronounced with soybean acid oil. In conclusion, soybean acid oil affects the
      intensity of yellow and red color of the yolk. Trained assessors detected
      differences in odor and aftertaste of eggs when soybean acid oil was included in
      the quail diet.

PMID- 29044325
TI  - Evaluation of embryotoxic and embryostatic effects of the aqueous extract of
      Rhizophora mangle and tannic acid on eggs and larvae of Aedes aegypti.
AB  - Rhizophora mangle is an abundant plant in mangroves and tannic acid is a
      polyphenol produced by the secondary metabolism of plants. The aim of the study
      was to evaluate the embryotoxic and embriostatic effects of the aqueous extract
      of R. mangle and synthetic tannic acid on eggs and larvae of Aedes aegypti. A.
      aegypti eggs were exposed in duplicate at concentrations of 250, 500, 750 and
      1000 ug/mL of extract and tannic acid for a period of 14 days. Mineral water was
      used as a negative control. The eggs were observed and counted in a
      stereomicroscope (1.2x). In all extract concentrations there was stimulation in
      hatching in relation to the control, but only in concentration of 750 mg/mL it
      was statistically significant. In tannic acid (250ug/ml) there was significant
      stimulus in hatching, but in 500, 750 and 1000 ug/mL there was significant
      inhibition. All concentrations of aqueous extract and tannic acid on larvae
      showed embryotoxic and embryostatic effects when compared to the control. The
      aqueous extract of R. mangle showed effect on hatching of A. aegypti eggs and
      synthetic tannic acid showed embryotoxic and embryostatic effects. On larvae,
      both the aqueous extract as tannic acid showed embryotoxic and embryostatic
      effects.

PMID- 29044326
TI  - In vitro antiparasitic activity and chemical composition of the essential oil
      from Protium ovatum leaves (Burceraceae).
AB  - Leishmaniasis and trypanosomiasis are globally widespread parasitic diseases
      which have been responsible for high mortality rates. Since drugs available for
      their treatment are highly hepatotoxic, nephrotoxic and cardiotoxic, adherence to
      therapy has been affected. Thus, the search for new, more effective and safer
      drugs for the treatment of these diseases is necessary. Natural products have
      stood out as an alternative to searching for new bioactive molecules with
      therapeutic potential. In this study, the chemical composition and antiparasitic
      activity of the essential oil from Protium ovatum leaves against trypomastigote
      forms of Trypanosoma cruzi and the promastigote forms of Leishmania amazonensis
      were evaluated. The essential oil was promising against trypomastigote forms of
      T. cruzi (IC50= 28.55 MUg.mL-1) and L. amazonensis promastigotes (IC50 = 2.28
      MUg.mL-1). Eighteen chemical constituents were identified by Gas Chromatography
      coupled to Mass Spectrometry (GC-MS) in the essential oil, whose major
      constituents were spathulenol (17.6 %), caryophyllene oxide (16.4 %), beta
      caryophyllene (14.0 %) and myrcene (8.4 %). In addition, the essential oil from
      P. ovatum leaves had moderate cytotoxicity against LLCMK2 adherent epithelial
      cell at the concentration range under analysis (CC50 = 150.9 MUg.mL-1). It should
      be highlighted that this is the first report of the chemical composition and anti
      Trypanosoma cruzi and anti-Leishmania amazonensis activities of the essential oil
      from Protium ovatum leaves.

PMID- 29044327
TI  - Generation of a triple-fluorescent mouse strain allows a dynamic and spatial
      visualization of different liver phagocytes in vivo.
AB  - Resident and circulating immune cells have been extensively studied due to their
      almost ubiquitous role in cell biology. Despite their classification under the
      "immune cell department", it is becoming increasingly clear that these cells are
      involved in many different non-immune related phenomena, including fetus
      development, vascular formation, memory, social behavior and many other
      phenotypes. There is a huge potential in combining high-throughput assays -
      including flow cytometry and gene analysis - with in vivo imaging. This can
      improve our knowledge in both basic and clinical cell biology, and accessing the
      expression of markers that are relevant in the context of both homeostasis and
      disease conditions might be instrumental. Here we describe how we generated a
      novel mouse strain that spontaneously express three different fluorescence
      markers under control of well-studied receptors (CX3CR1, CCR2 and CD11c) that are
      involved in a plethora of stages of cell ontogenesis, maturation, migration and
      behavior. Also, we assess the percentage of the expression and co-expression of
      each marker under homeostasis conditions, and how these cells behave when a local
      inflammation is induced in the liver applying a cutting-edge technology to image
      cells by confocal intravital microscopy.

PMID- 29044328
TI  - Carbon dioxide/methanol conversion cycle based on cascade enzymatic reactions
      supported on superparamagnetic nanoparticles.
AB  - The conversion of carbon dioxide into important industrial feedstock is a subject
      of growing interest in modern society. A possible way to achieve this goal is by
      carrying out the CO2/methanol cascade reaction, allowing the recycle of CO2 using
      either chemical catalysts or enzymes. Efficient and selective reactions can be
      performed by enzymes; however, due to their low stability, immobilization
      protocols are required to improve their performance. The cascade reaction to
      reduce carbon dioxide into methanol has been explored by the authors, using,
      sequentially, alcohol dehydrogenase (ADH), formaldehyde dehydrogenase (FalDH),
      and formate dehydrogenase (FDH), powered by NAD+/NADH and glutamate dehydrogenase
      (GDH) as the co-enzyme regenerating system. All the enzymes have been immobilized
      on functionalized magnetite nanoparticles, and their reactions investigated
      separately in order to establish the best performance conditions. Although the
      stepwise scheme led to only 2.3% yield of methanol per NADH; in a batch system
      under CO2 pressure, the combination of the four immobilized enzymes increased the
      methanol yield by 64 fold. The studies indicated a successful regeneration of
      NADH in situ, envisaging a real possibility of using immobilized enzymes to
      perform the cascade CO2-methanol reaction.

PMID- 29044329
TI  - Beneficial effects of bio-controlling agent Bacillus cereus IB311 on the
      agricultural crop production and its biomass optimization through response
      surface methodology.
AB  - Disease in agricultural field is a big problem that causes a massive loss in
      production. In this present investigation, we have reported a soil-borne
      bacterium Bacillus cereus IB311 which is antagonistic to plant pathogens
      (Pseudomonas syringae and Agrobacterium tumefaciens), and could make a
      substantial contribution to the prevention of plant diseases. To prove the
      practical application, the strain was directly applied in agricultural field. The
      results demonstrated that B. cereus IB311 has increased the production (20% and
      26% in term of average pod number per plant, average seed number per pod, and
      seed yield per experimental plot) in ground nut (Arachis hypogaea var. Koushal,
      G201) and sesame (Sesamum indicum var. Kanak), respectively. To reduce the
      production cost, the biomass production was optimized through response surface
      methodology (RSM). Interactions of three variables (glucose, beef extract and
      inoculum) were studied using Central Composite Design. According to our analysis,
      optimum production of Bacillus cereus IB311 (5.383 ug/ mL) may be obtained at
      glucose 1.985%, beef extract 1.615% and inoculums size 0.757%. Therefore, we
      strongly believe that the application of this strain in agricultural field as bio
      controlling agent will definitely enhance the production yield and will reduce
      the disease risk.

PMID- 29044330
TI  - Purification and characterization of a thermostable alkaline cellulase produced
      by Bacillus licheniformis 380 isolated from compost.
AB  - During composting processes, the degradation of organic waste is accomplished and
      driven by a succession of microbial populations exhibiting a broad range of
      functional competencies. A total of 183 bacteria, isolated from a composting
      process, were evaluated for cellulase activity at different temperatures (37, 50,
      60, and 70 degrees C) and pH values. Out of the 22 isolates that showed activity,
      isolate 380 showed the highest cellulase activity. Its ability to produce
      cellulase was evaluated in culture medium supplemented with carboxymethyl
      cellulose, microcrystalline cellulose, wheat straw, and rice husk. The culture
      medium supplemented with carboxymethyl cellulose induced higher enzyme activity
      after 6 hours of incubation (0.12 UEA mL-1 min-1). For wheat straw and rice husk,
      the results were 0.08 UEA mL-1 min-1 for both, while for microcrystalline
      cellulose, 0.04 UEA mL-1 min-1 were observed. The highest carboxymethyl cellulase
      activity was observed at 60 degrees C (0.14 UEA mL-1 min-1) for both crude and
      partially purified enzyme after 30 and 120 min of incubation, respectively.
      Alkalinization of the medium was observed during cultivation in all substrates.
      The cellulase had a molecular mass of 20 kDa determined by SDS-Page. Isolate 380
      was identified as Bacillus licheniformis. This work provides a basis for further
      studies on composting optimization.

PMID- 29044331
TI  - CKD after AKI: time to be alert.

PMID- 29044332
TI  - Obesity - the verse and the reverse.

PMID- 29044333
TI  - Hospital do Rim, Sao Paulo: A World Leader in Kidney Transplantation.

PMID- 29044334
TI  - Declaration of the Vatican Pontifical Academy of Sciences.

PMID- 29044335
TI  - Brazilian Chronic Dialysis Survey 2016.
AB  - INTRODUCTION: National chronic dialysis data are important for the treatment
      planning. OBJECTIVE: To report data of the annual survey of the Brazilian Society
      of Nephrology about chronic kidney disease patients on dialysis in July 2016.
      METHODS: A survey based on data of dialysis centers from the whole country. The
      data collection was performed by using a questionnaire filled out on-line by the
      dialysis centers. RESULTS: 309 (41%) of the dialysis units in the country
      answered the questionnaire. In July 2016, the total estimated number of patients
      on dialysis was 122,825. The estimated prevalence and incidence rates of chronic
      maintenance dialysis were 596 (range: 344 in the North region and 700 in the
      Southeast) and 193 patients per million of population (pmp), respectively. The
      annual incidence rate of patients with diabetic nephropathy was 79 pmp. The
      annual gross mortality rate was 18.2%. For prevalent patients, 92% were on
      hemodialysis and 8% on peritoneal dialysis, and 29,268 (24%) were on a waiting
      list of renal transplant. A venous catheter was the vascular access for 20.5% of
      the hemodialysis patients. The prevalence rates of positive serology for
      hepatitis B and C showed a tendency to reduce from 2013 (1.4% and 4.2%,
      respectively) to 2016 (0.7% and 3.7%, respectively). CONCLUSION: The absolute
      number and the prevalence and incidence rates of patients on dialysis continue to
      rise steadily; the gross mortality rate remained stable. Regional inequities are
      evident in these rates.

PMID- 29044336
TI  - The impact of body mass index (BMI) variation on mortality of incident elderly
      patients on peritoneal dialysis: a joint model analysis.
AB  - INTRODUCTION: Data on impact of high body mass index (BMI) on mortality of
      patients on peritoneal dialysis (PD), especially among elderly, are inconsistent.
      Objective: To evaluate impact of BMI on cohort of incident elderly PD patients
      over time. METHODS: Prospective multicenter cohort study (December / 2004
      October/2007) with 674 patients. Socio-demographic and clinical data evaluated
      with patients followed until death, transfer to hemodialysis (HD), recovery of
      renal function, loss of follow-up or transplant. Patients were divided into
      incident on renal replacement therapy (RRT) for PD (PD first: 230) and
      transferred from hemodialysis (HD first: 444). Analysis was performed comparing
      these two groups using chi-square or Kruskal Wallis. Similar analysis was used to
      compare patients on automated peritoneal dialysis (APD) vs. continuous ambulatory
      peritoneal dialysis (CAPD). Data were compared between patients according to BMI
      by ANOVA, Kruskal Wallis or chi-square. For analysis of survival, Kaplan Meier
      method was used and to adjust confounding variables, Cox regression proportional
      hazard. Joint model for longitudinal and time-dependent data was conducted,
      assessing impact that a longitudinal variable displays on time of survival.
      RESULTS: Malnourished patients (76.79 +/- 7.53 years) were older (p < 0.0001)
      with higher percentage of death (44.6%, p = 0.001); diabetes mellitus showed high
      prevalence in obese patients (68%, p < 0.0001); higher blood pressure levels (p =
      0.002) were present in obese and overweight patients. CONCLUSIONS: Increased BMI
      variation over time proved to be a protective factor, with a decrease of about 1%
      in risk of death for every BMI unit earned.

PMID- 29044337
TI  - Beneficial effects of intradialytic cardiopulmonary rehabilitation.
AB  - INTRODUCTION: Patients on hemodialysis (HD) present high mortality from
      cardiovascular complications and high morbidity, including decreasing functional
      capacity and quality of life. OBJECTIVE: To analyze clinical and laboratory
      responses of patients in HD to intradialytic cardiopulmonary rehabilitation on an
      outpatient basis. METHODS: We evaluated 14 patients in a prospective study for 8
      months using cardiopulmonary rehabilitation protocol (CRehab) consisted of
      intradialytic aerobic exercise with a cycle ergometer. We analyzed heart rate
      (HR), systolic (SBP) and diastolic blood pressure (DBP), peripheral oxygen
      saturation (SpO2) and modified Borg scale. We evaluated cardiac function by
      echocardiogram, functional capacity by six minutes walk test (6MWT), and quality
      of life by SF-36 survey, before and after CRehab. Biochemical data and KT/Vsp
      were collected form medical records. RESULTS: During CRehab, the results of HR,
      SBP, DBP, SpO2 and Borg scale showed no significant changes. 6MWT test showed
      progressive increase in the distance covered (p < 0.001) as well as a reduction
      in the scale of Borg post-6MWT (p = 0.009). There was no significant change in
      any biochemical data or in KT/Vsp. There was increase in left ventricular
      ejection from 65.7 +/- 10.2% to 73.6 +/- 10.1% (p = 0.028) and in left
      ventricular diastolic diameter (p = 0.027). According to SF-36 survey, patients
      showed improvement in three areas: physical role functioning (p = 0.012), bodily
      pain (p = 0.007) and vitality (p = 0.009). CONCLUSION: The intradialytic CRehab
      applied in this population was safe and allowed objective improvement of
      functional capacity and exercise tolerance, subjective improvement in the
      perception of effort, significant increase in cardiac function and better quality
      of life in different domains.

PMID- 29044338
TI  - Nutritional profile of hemodialysis patients concerning treatment time.
AB  - INTRODUCTION: The mortality of the population with chronic kidney disease (CKD)
      on hemodialysis (HD) is very high and the protein-energy malnutrition stands out
      as one of the most common consequences in relation to this condition. OBJECTIVE:
      To evaluate the association between time of hemodialysis and nutritional
      parameters of patients. METHODS: It is a cross-sectional study with secondary
      data, developed of the University Hospital of the Federal University of Juiz de
      Fora (HU/UFJF). This study was approved by the Research Ethics Committee (No
      1.233.142), a total of 36 patients. The medical records and collected data were
      analyzed for anthropometric markers, biochemical and diet, considering two
      groups: HD time less than three and greater than or equal to three years.
      RESULTS: There was reduction of mass of somatic protein with increased duration
      of HD. In relation to food intake was observed that in patients with increased
      duration of dialysis, an increase in average consumption of protein / kg of
      weight, calories, phosphorus and potassium, with a significant difference from
      the mean protein intake / kg (p = 0.04) and phosphorus (p = 0.045). Increasing HD
      time has altered body composition of patients, indicating a decline in the
      nutritional status of these individuals. CONCLUSION: HD patients are a risk group
      for protein-energy malnutrition, where HD time interferes with the nutritional
      status and food profile of the patient. The group HD time greater than or equal
      to 3 years presented worsening nutritional status.

PMID- 29044339
TI  - Metabolic acidosis in hemodialysis patients: a review.
AB  - Metabolic acidosis is highly prevalent in hemodialysis patients. The disorder is
      associated with increased mortality and its deleterious effects are already
      present in the predialysis phase of chronic kidney disease. Metabolic acidosis
      has been linked to progression of chronic kidney disease, changes in protein and
      glucose metabolism, bone and muscle disorders and cardiovascular disease. At
      present, the control of metabolic acidosis in hemodialysis is mainly focused on
      the supply of bicarbonate during dialysis session, but further studies are needed
      to set the optimum target serum bicarbonate and the best concentration of the
      bicarbonate dialysate. The present study reviews pathophysiological and
      epidemiological aspects of metabolic acidosis in hemodialysis patients and also
      addresses its adverse effects and treatment.

PMID- 29044340
TI  - Renouncement of renal replacement therapy: withdrawal and refusal.
AB  - Renouncement of renal replacement therapy (RRT) is a medical dilemma. This review
      covers the concept, the magnitude, the prognosis, and discusses strategies and
      management approaches about this subject in patients with CKD and AKI. Evidence
      suggests that refusal is more frequent and carries a more guarded prognosis than
      withdrawal of RRT. When RRT is not expected to be beneficial in terms of survival
      or quality of life, conservative treatment and palliative care are alternatives.
      We review the historical evolution of guidelines about renouncement of RRT and
      palliative care, and highlight the absence of specific recommendations in Brazil.
      However renouncement of RRT may be ethically and legally accepted in Brazil, as
      the right to a dignified death. Longer life expectancy, economic pressures, and
      greater awareness will require a more detailed discussion about indications and
      sustainable use of RRT, and possibly the elaboration of national guidelines.

PMID- 29044341
TI  - The use of antimicrobials in septic patients with acute kidney injury.
AB  - Sepsis is the most common cause of death in critically ill patients and it may be
      associated with multiorgan failure, including acute kidney injury (AKI). This
      situation can require acute renal support and increase mortality. Therefore, it
      is essential to administrate antimicrobials in dosis to achieve adequate serum
      levels, preventing overdosis and drug toxicity or underdosing and risk for
      resistance to antibiotics and higher mortality. To date, there aren't validated
      guidelines on antibiotic dosis adjustment in septic patients with AKI and the
      recommendations are extrapolated from studies conducted in non-critical patients
      with chronic kidney disease in end stage receiving chronic renal replacement
      therapy. This study aimed to review and discuss the complexity of that issue,
      considering the several factors related to the drugs removal: critically ill
      patient characteristics, antimicrobial properties and dialysis method.

PMID- 29044342
TI  - Acquired cystic kidney disease in allograft with long-standing poor function.
AB  - Acquired Cystic Kidney Disease (ACKD) is regarded as a common late condition of
      end stage renal damage and expresses its most important features when associated
      with long term hemodialysis. ACKD is also widely known as a premalignant lesion.
      Its occurrence in chronically rejected renal allografts is rare and its frequency
      and behavior in this setting are not well known. Herein we report a case of ACKD
      in a long standing nonfunctional allograft (215 months) which is not associated
      with malignancy and briefly review the related literature.

PMID- 29044343
TI  - Case report: is low alpha-Gal enzyme activity sufficient to establish the
      diagnosis of Fabry disease?
AB  - Fabry disease is an X-linked lysosomal storage disease due to alpha-galactosidase
      A (alpha-Gal A) deficient activity which leads to the accumulation of
      glucoesphingolipids, such as globotriaosilceramide. There are over 700 known
      mutations of the enzyme gene, and most of them cause Fabry Disease. This case
      report describes a hemodialysis patient with a rare and controversial GLA gene
      mutation, the D313Y. The medecial investigation confirmed that D313Y is an alpha
      galactosidase A sequence variant that causes pseudo deficient enzyme activity in
      plasma but not Fabry disease. Thus, clinical symptoms that prompted Fabry disease
      investigation could not be attributable to Fabry disease and therefore enzyme
      replacement therapy was not indicated.

PMID- 29044344
TI  - Persistent severe hypokalemia: Gitelman syndrome and differential diagnosis.
AB  - The main causes of hypokalemia are usually evident in the clinical history of
      patients, with previous episodes of vomiting, diarrhea or diuretic use. However,
      in some patients the cause of hypokalemia can become a challenge. In such cases,
      two major components of the investigation must be performed: assessment of
      urinary excretion potassium and the acid-base status. This article presents a
      case report of a patient with severe persistent hypokalemia, complementary
      laboratory tests indicated that's it was hypomagnesaemia and hypocalciuria
      associated with metabolic alkalosis, and increase of thyroid hormones. Thyrotoxic
      periodic paralysis was included in the differential diagnosis, but evolved into
      euthyroid state, persisting with severe hypokalemia, which led to be diagnosed as
      Gitelman syndrome.

PMID- 29044345
TI  - First Report of Granulicatella sp. Endocarditis in a Kidney Transplant Patient.
AB  - Granulicatella and Abiotrophia are genera of fastidious Gram-positive cocci
      commensal of the oral, genitourinary, and intestinal flora. We report the first
      case of infective endocarditis caused by Granulicatella sp. in a kidney
      transplant recipient. A 67-year-old male kidney transplant recipient was admitted
      to the hospital for investigation of fever, abdominal pain, and diarrhea. On
      physical examination, he was dehydrated. Laboratory tests identified impaired
      renal function (creatinine level of 15.5 mg/dl; reference, 3.0 mg/dl), metabolic
      acidosis, and electrolyte disturbances. Cryptosporidium sp. was identified as the
      cause of the diarrhea, and the infection was treated with nitazoxanide. On
      admission, cultures of blood, urine, and stool samples were negative.
      Echocardiography results were normal. Despite the antimicrobial treatment, the
      fever persisted. A transthoracic echocardiogram revealed infective endocarditis
      of the mitral valve, and Granulicatella spp. were isolated in blood cultures.
      Although the patient was treated with penicillin and amikacin, he evolved to
      septic shock of pulmonary origin and died. Infective endocarditis caused by
      Granulicatella sp. should be suspected in cases of culture-negative endocarditis.

PMID- 29044346
TI  - Raised questions about the proposed adjustment in CKD classification in the
      elderly.
AB  - In a recent review article, authors suggest lowering the diagnostic threshold for
      chronic kidney disease (CKD) in the elderly population. Here, it is discussed the
      possible implications of that proposed change.

PMID- 29044347
TI  - Reply to Letter to the Editor.

PMID- 29044348
TI  - Sonographically abnormal placenta: an association with an increased risk poor
      pregnancy outcomes.
AB  - BACKGROUND: The placenta is a most interesting but unfortunately often ignored
      and misunderstood organ. Placental abnormalities, therefore, can be an "early
      warning system" for fetal problems. A complete prenatal sonographic examination
      of the placenta is an essential component as its abnormalities can have a direct
      effect on fetal or maternal outcomes, obstetrical management and future
      fertility. OBJECTIVE: To determine whether any association exists between the
      finding of an increased thickness of placenta, abnormal placenta shape, placental
      calcification, placental lake and abnormal cord insertion site at 20-22 and 30-32
      weeks gestation with an increased risk of uteroplacental complications or a poor
      pregnancy outcome. METHODOLOGY: A real-time ultrasound was used at the time of
      detail scan (at 20-22 weeks gestation) and at 30-32 weeks gestation to look for
      placenta appearance, fetal growth and anomaly. The main outcome measures were
      risk of hypertension disease in pregnancy, fetal growth restriction and poor
      fetal outcomes such as low Apgar score and low cord pH. RESULT: The majority of
      the participants were Malay (77.9%). Abnormal placenta found at both gestations
      were placental lakes and thickness, and only one case had marginal cord
      insertion. Approximately 6% of the cases were confirmed placenta previa. No
      abnormal shape or abnormal calcification found at both gestations. About 10%
      patient developed hypertensive disease in pregnancy, 15% of the fetus was found
      to have growth restriction and another 16% have low umbilical cord pH. Majority
      of them delivered at term (90%) and via vaginal delivery (81%). There was no
      significance between presence of abnormal placental lake and thickness at both
      gestations with the maternal and fetal outcome. CONCLUSION: Presence of abnormal
      placental thickness and lakes at 30-32 weeks scan associated with maternal
      hypertensive disease, fetal growth restriction and low umbilical cord pH, however
      these were not statistically significant.

PMID- 29044349
TI  - High risk of brain tumors in farmers: a mini-review of the literature, and report
      of the results of a case control study.
AB  - Even though a relationship between farmer work and the development of brain
      tumors was suggest by the scientific literature, a small number of italian
      studies investigate on the impact of this job on the cancer morbidity of farmer
      population. The informations about this case-control study were obtained from
      patients recruited in the Neurosurgical Department of the University-Hospital of
      Pisa, Italy, from 1990 to 2000. One hundred and seventy-four, newly diagnosed
      cases of brain tumors (glioma and meningiomas, histologically confirmed), were
      recruited, such as 522 controls (with other non tumoral neurologic diseases:
      trauma, etc), by matching cases and controls (1:3), for age (+/- 5 years) and
      gender. Cases and controls were interviewed in the Neurosurgical Department,
      University-Hospital of Pisa, Italy, and the occupational histories of cases and
      controls were compared. Cases and controls have showed a statistically
      significant difference, based on their occupation (agricultural vs. non
      agricultural). We observed a significant association among brain tumors and rural
      activity in evaluated patients (P=0.008). Further studies regarding this
      population group are needed, to determine the causes for the increased risk of
      this cancer, particularly in regions where there is an intense agricultural
      activity and where pesticides are used. Furthermore, a subsequent reevaluation in
      other patients collected in more recent years will be needed to evaluate the
      trend of this association.

PMID- 29044350
TI  - A singular case of asphyxia by choking on a handkerchief: accidental event or
      suicide to "shut-up" spirits.
AB  - Choking in adults can prove fatal, despite resuscitation attempts. The manner of
      death can be natural, homicide or accident. When a death is due to choking, one
      must consider what conditions contributed to or predisposed the person to choking
      (eg. alcohol, drugs and physical and mental impairments). Homicidal deaths by
      choking are relatively uncommon, being more frequently accidental. The diagnosis
      of death by choking is made at autopsy when the airway is found occluded. If the
      individual had an occluded airway and the object or food was removed during
      resuscitation, the only way to make the diagnosis would be on the history. Here,
      we present a case of asphyxia (accidental or suicidal) by choking on a
      handkerchief in a patient with a long history of schizophrenia. The woman had
      attempted a previous suicide driven by evil spirits coming from inside her body,
      especially from the head and throat; in order to "shut-up" the spirit, she was
      trying to suffocate it with her hands or by a belt from her pants.

PMID- 29044351
TI  - Surgical management of Necrotizing Enterocolitis in an Incredibly Low Birth
      Weight infant and review of the Literature.
AB  - Survival of preterm infants have dramatically improved over the last decades.
      Nonetheless, infants born preterm remain vulnerable to many complications,
      including necrotizing enterocolitis (NEC). The severity of the disease and the
      mortality rate are directly correlated with decreasing gestational age and birth
      weight. Despite surgical treatment mortality rate remains very high in extremely
      premature infants, especially in newborns at the lowest limit of viability.
      Survival of infants of birth weight (BW) below 750 g has been increasingly
      reported in recent years, however the overall mortality in extremely low "BW"
      infants (ELBW) requiring surgery for NEC has not decreased over the past years.
      We describe our experience with a male preterm infant who survived after an
      ileostomy procedure for Bell stage II NEC, with improving neuromotor skills at 2
      years follow up. Although standard indication to surgery is Bell stage III, in
      our case the choice of minimal laparotomy, exploration of the bowel and ileostomy
      at Bell stage II was safe and effective. Our experience suggest that surgery has
      not a negative impact on survival and ileostomy could prevent further damage of
      the bowel in NEC. We hypothesize that indication to surgery at an earlier stage
      may prevent further progression of the disease without a significantly negative
      impact on survival. Further studies are needed to confirm the appropriateness of
      this approach in ELBW infants.

PMID- 29044352
TI  - [Sulphurous vaginal douching and vulvovaginal atrophy].
AB  - OBJECTIVE: During climacteric the reduction or interruption of estrogenic
      stimulus determines a gradual atrophy of the tissues of the urogenital
      tract.Vulvovaginal atrophy can be cause of dryness, itch, burning, and
      dyspareunia. Vulvovaginal atrophy is associated also with depression. Hence the
      importance of an appropriate treatment of the vulvovaginal atrophy. Between
      therapeutic options we can add, particularly for women who suffer only from
      vaginal symptoms, the spa therapy that uses mineral waters with benefic effects
      on vaginal tissue wellness and health. On the basis of considerations described
      above and on the insufficient literature data, the objective of our single-arm
      pilot study has been to evaluate, in women suffering from vulvovaginal atrophy,
      the effects and safety of a vaginal douching cycle with sulphurous mineral water
      and impact on depression disorder frequently observed. PATIENTS AND METHODS: The
      study was conducted on 24 women affected by vulvovaginal atrophy; mean age:57+/
      11 years; age range:42-81 years. The subjects were treated, for 2 weeks, with
      sulphurous vaginal douching from Terme of Telese S.p.A. (Benevento-Italy). At the
      beginning and at the end of the SPA treatment the following symptoms were
      evaluated: dryness, burning, itch, dyspareunia and leucorrhoea (using VAS scale);
      the impact on psychological distress (using S.D.S. Zung-test). RESULT: At the end
      of the spa treatment, the mean values+/-SD, compared to baseline, have showed a
      significant (p<0.05) reduction in leucorrhoea (-88%), in vulvar itch (-79%), in
      vaginal burning (-71%), in vaginal dryness (-65%) with an improvement of
      psichological distress as demonstrated by S.D.S. Zung-test. CONCLUSION: The data
      of this single-arm pilot clinical trial show that the sulphurous vaginal douching
      cycle can be considered very useful in women suffering from vulvovaginal atrophy
      with improving of the quality of life and social relationship.

PMID- 29044353
TI  - The daily-practiced post-partum hemorrhage management: an Italian
      multidisciplinary attended protocol.
AB  - Postpartum hemorrhage (PPH) is one of the most frequent causes of mortality and
      morbidity in the obstetric population globally, causing about a quarter of
      maternal deaths yearly, and is the leading cause of maternal death worldwide. The
      management of PPH remains a topic of great debate, even in view of new diagnostic
      and therapeutic possibilities in recent years, for which, however, the body of
      evidence available thus far is still scarce, as the standard values are lacking.
      The protocol hereby presented was developed after a literature review and during
      several meetings of an Italian multidisciplinary task group of specialists
      adopting a modified Delphi method, and is the result of the synthesis of
      therapeutic operational protocols for the treatment of PPH applied by the
      different specialties within the team. This protocol is intended to represent a
      practical proposal to support clinicians in the management of a particularly
      complex event that requires the intervention of a multidisciplinary team and the
      implementation of dedicated management protocols.

PMID- 29044354
TI  - Protocol for the evaluation of a chronic care model experience in Rome.
AB  - INTRODUCTION: Chronic diseases are the leading cause of death and disability in
      almost all over the world; in Europe causing over 9 million deaths per year
      according to WHO estimates. A promising health organization model for chronic
      disease management is represented by the Chronic Care Model (CCM). In the 12th
      district of the ASL Roma 2 since 4 years was implemented a CCM for the management
      of patients affected by diabetes and/or at high cardiovascular risk. OBJECTIVE:
      Aim of this study is to evaluate the effectiveness of the Chronic Care Model
      (CCM) for the management of chronic disease in terms of mortality reduction,
      avoidable hospitalizations reduction and improvement of clinical parameters.
      MATERIALS AND METHODS: A retrospective cohort study will involve patients of 12th
      district of the ASL Roma 2 affected by diabetes and at high cardiovascular risk
      assisted through the CCM. Their health outcomes will be compared with those of
      patients in the same clinical conditions, residents in the same district but not
      assisted with CCM. The sample will be composed by adults (> 18 years) with a
      diagnosis of diabetes mellitus type 2 (DM2) or metabolic syndrome and / or
      arterial hypertension (IT) and two or more risk factors. Outcomes will be
      mortality from all causes and from causes related to DM and IT, preventable
      hospitalizations as defined in the Prevention Quality Indicators (PQI) by the
      Agency for Healthcare Research and Quality, and 10 clinical parameters. The data
      sources will be the records of causes of death (RENCAM), the hospital discharge
      records (SDO) and information systems for primary healthcare. CONCLUSION: Data
      from the experience of CCM in Tuscany seem promising especially in the evaluation
      of patient satisfaction and clinical outcomes particularly on cardiovascular and
      neurological complications and long-term mortality.

PMID- 29044355
TI  - The effects of low level laser irradiation on proliferation of human dental pulp:
      a narrative review.
AB  - Mesenchymal stem cells (MSCs) have the capability for self-renewal,
      proliferation, and differentiation in various types of specialized cells, so they
      are very important in cellular therapies. MSC from dental pulp are simply
      obtainable and have high proliferative capability. Among the therapies that can
      stimulate the proliferation of certain cell types, low-level laser therapy (LLLT)
      stands out. The target of this study is to perform a literature review to
      investigate these effects of low-level laser irradiation on proliferation of
      human dental pulp.The electronic search of scientific papers was conducted in the
      Lilacs, Scielo, Medline and PubMed databases through scientific articles
      published in national and international journals in the past 20 years.The results
      of this review suggest that LLLT may be a useful and important tool for future
      advances in cell therapy and tissue engineering associated to stem cells. Studies
      on cell therapy for regenerating dental tissues has already been done, and shows
      promising results.

PMID- 29044356
TI  - [Active surveillance evaluation of anti-HPV vaccine adverse events in Umbria
      region].
AB  - AIMS: The study is a part of the "Active surveillance of adverse events following
      HPV vaccination" project conducted in order to actively register all common
      adverse events in girls 9-26 years after anti-HPV vaccination. METHODS: It is a
      multicenter cohort study which included 12 Regions and 87 local health
      authorities, coordinated by the National Centre for Epidemiology, Surveillance
      and Health Promotion (CNESPS) ISS. We included all adolescents, 12 years old,
      actively contacted for HPV vaccination, as well as all women aged 9-26 years who
      recived, in the period under review, the same vaccination at the local health
      authorities in Spoleto. RESULT: Out of 147 girls enrolled in the program, only
      102 have reported the diary filled after the first vaccine dose, 62 and 88
      respectively after the second and third dose. The filled diaries shown that
      adverse events, if any, have occurred almost exclusively during the first 5 days
      of vaccination, with a strong prevalence of local reactions (erythema, pain and
      swelling at the injection site) followed by headache and muscles pain.
      CONCLUSION: Even though the results show a high number of reported adverse
      events, mainly due to the detection method (active surveillance), they are mild
      or moderate in almost all the cases. This is in line with that seen in previous
      trials.

PMID- 29044358
TI  - [Perche la legionellosi e una tra le piu temibili ICA].
AB  - La Legionellosi e una polmonite che puo presentare un decorso variabile a seconda
      se i soggetti colpiti risiedono nel loro domicilio, sono ospiti di strutture
      recettive o sono ospedalizzati. In ambito ospedaliero, che annovera questa
      patologia tra le piu pericolose Infezioni Correlate all'Assistenza (ICA), si
      registrano decisamente i casi piu gravi e assai spesso letali. Gli errori nella
      Valutazione del Rischio e negli interventi di risanamento contribuiscono alla
      proliferazione all'interno delle condutture idriche di un temibile microrganismo
      che puo essere eliminato o ridotto solo con un approccio multidisciplinare.

PMID- 29044357
TI  - Oral health sentinel-based surveillance: a pilot study on dentinal
      hypersensitivity pain.
AB  - Aim of the study is to assess the development of a structured sentinel system for
      oral health data collection at national level. Furthermore, this pilot study aims
      to investigate the prevalence data on dentinal sensitivity pain collected through
      a nationwide network of epidemiological sentinels (dental hygienists). Each
      sentinel was given a specific number of examinees and periodicity of data
      collection. Overall, 116 adults were recruited from 19 Regions, 42,24% male and
      57,76% female, with a mean age of 26. DH result was consistent with literature
      data, being 45%. All sentinel completed the standard forms and assured a good
      compliance. The overall good customer satisfaction assures adhesion of the
      sentinels to the procedure, and the regular data collection. The pilot study
      proved the effectiveness of a structured nationwide network of epidemiological
      sentinels (dental hygienists) for oral health data collection at national level.
      This methodology can be an essential starting point for periodic comparative
      studies.

PMID- 29044359
TI  - Management della retinopatia diabetica e dell'edema maculare diabetico: linee
      guida "Euretina 2017".
AB  - Si prevede che la malattia diabetica con tutte le sue complicanze avra un forte
      aumento di incidenza con un grosso impatto socioeconomico nei prossimi decenni in
      tutto il mondo. Pertanto ben si comprende l'importanza di individuare attraverso
      una fine diagnostica quanto piu precocemente la comparsa dei sintomi diabetici,
      migliorare lo stile di vita ed impostare cure efficienti. Riportiamo la serie di
      raccomandazioni EURETINA 2017, dei maggiori esperti in Europa per la gestione
      della malattia diabetica e delle complicanze della retina. Per combattere questa
      "pestilenza" occorre un team medico preparato. Il trattamento laser e stato
      considerato sino a non molto tempo fa il Gold standard della retinopatia
      diabetica e dell'edema diabetico (RD e EMD). Recenti studi hanno dimostrato,
      invece, che si possono raggiungere risultati migliori mediante l'iniezione
      diretta di farmaci nella cavita vitreale. In particolare e emerso terapia di
      prima linea, molecole in grado di inibire il fattore di crescita endoteliale
      vascolare (anti VEGF) mentre non e piu raccomandata la fotocoagulazione laser per
      il trattamento del DME. Nell'ambito delle molecole farmacologiche gli steroidi
      hanno mantenuto un ruolo nella gestione del DME cronicamente persistente.

PMID- 29044361
TI  - Percutaneous Myotomy With a Small Needle-Knife and Lipoinjection for Treatment of
      Glabellar Frown Lines.
AB  - Background: Glabellar frown lines are a common aesthetic concern, and minimally
      invasive techniques to treat frown lines have become popular. Objectives: The
      authors developed a technique to minimize frown lines by means of percutaneous
      myotomy with a small needle-knife and lipoinjection. Methods: Sixty-nine patients
      underwent treatment of the glabellar frown lines in a prospective study.
      Percutaneous myotomy of the corrugator supercilii and procerus was conducted with
      a small needle-knife, and autologous fat was transferred to the glabellar region.
      Two independent investigators assessed improvement of the glabellar frown lines
      by applying the Merz Facial Wrinkle Scale preoperatively and 6 months
      postoperatively. Improvement by >=1 point was regarded as a response to
      treatment. Patients also conducted a self-assessment based on the Global
      Aesthetic Improvement Scale. Results: The mean follow-up period was 8 months. The
      evaluators determined that the glabellar frown lines of 62 patients (89.9%)
      responded to treatment. For 4 patients (5.8%), the frown lines were partially
      improved, and the frown lines did not improve for 3 patients (4.3%). In a self
      assessment, 64 patients (92.8%) perceived improvement in their frown lines 6
      months postoperatively. No serious complications were recorded. Conclusions:
      Treatment of glabellar frown lines by percutaneous myotomy with a small needle
      knife and lipoinjection is reliable and minimally invasive. Level of Evidence: 4.

PMID- 29044362
TI  - Personal Evolution in Thighplasty Techniques for Patients Following Massive
      Weight Loss.
AB  - Background: Lockwood described the importance of Colles' fascia anchoring in
      medial thighplasty to reduce morbidity associated with the procedure. However,
      this maneuver may still have complications including traumatic dissection,
      prolonged edema, and potential wound healing ramifications form increased
      tension. Alternatively, we suggest orienting tension in medial thighplasty for
      massive weight loss (MWL) patients in the horizontal vector rather than a
      vertical direction, negating the need for Colles' fascia anchoring. Objectives:
      To compare the morbidities, complications, and outcomes between Colles' fascia
      suture fixation (CFSF) and horizontal vector fixation (HVF) in medial
      thighplasties in MWL patients. Methods: A retrospective chart review was
      conducted on an Institutional Review Board approved database of MWL patients who
      had medial thighplasty between October 2004 and March 2014. Patient demographics
      and surgical outcomes were reviewed between those MWL patients with CFSF and HVF.
      Results: Of 65 post-MWL patients, 26 (40.0%) patients were in the CFSF group, and
      39 (60.0%) patients were in the HVF group. The 2 groups had statistically
      equivocal preoperative characteristics and comorbidities. Intraoperatively, the
      HVF group had increased use of barbed suture (92.3% vs 30.6%, P < 0.0001) and
      liposuction (71.8% vs 26.9%, P < 0.0001). Postoperatively, the HVF group had
      decreased incidence of infection (5.1% vs 23.0%, P = 0.051) and lymphocele/seroma
      (10.3% vs 34.6%, P = 0.0257). No statistical differences were observed for
      dehiscence, necrosis, or hematoma. Conclusions: HVF for medial thighplasty in MWL
      patients is a safe and effective procedure, with a lower complication profile
      than CFSF. Furthermore, the incorporation of barbed sutures and/or liposuction
      may help to achieve optimal results. Level of Evidence: 3.

PMID- 29044363
TI  - The Value of a Resident Aesthetic Clinic: A 7-Year Institutional Review and
      Survey of the Chief Resident Experience.
AB  - Background: With the evolving plastic surgery training paradigm, there is an
      increasing emphasis on aesthetic surgery education during residency. In an effort
      to improve aesthetic education and to encourage preparation for independent
      practice, our institution has supported a resident-run aesthetic clinic for over
      two decades. Objectives: To provide insight into the educational benefits of a
      resident-run cosmetic clinic through longitudinal resident follow up and
      institutional experiential review. Methods: A retrospective review was conducted
      to identify all clinic-based aesthetic operations performed between 2009 and
      2016. To capture residents' perspectives on the cosmetic resident clinic,
      questionnaires were distributed to the cohort. Primary outcome measures included:
      volume and types of cases performed, impact of clinic experience on training,
      confidence level performing cosmetic procedures, and satisfaction with chief
      clinic. Unpaired t tests were calculated to compare case volume/type with level
      of confidence and degree of preparedness to perform cosmetic procedures
      independently. Results: Overall, 264 operations performed by 18 graduated chief
      residents were reviewed. Surveys were distributed to 28 chief residents (71.4%
      completion rate). Performing twenty or more clinic-based procedures was
      associated with higher levels of preparedness to perform cosmetic procedures
      independently (P = 0.037). Residents reported the highest confidence when
      performing cosmetic breast procedures when compared to face/neck (P = 0.005),
      body/trunk procedures (P = 0.39), and noninvasive facial procedures (P = 0.85).
      Conclusions: The continued growth of aesthetic surgery highlights the need for
      comprehensive training and preparation for the new generation of plastic
      surgeons. Performing cosmetic procedures in clinic is a valuable adjunct to the
      traditional educational curriculum and increases preparedness and confidence for
      independent practice.

PMID- 29044364
TI  - Outcome After Breast Reduction Considering Body Mass Index and Resection Amount.
AB  - Background: It is presumed that breast reduction improves patients' quality of
      life and promotes weight loss. Preoperative body mass index (BMI) and the amount
      of breast tissue (breast reduction amount [BRA]) in proportion to the patient's
      body weight are important variables to affect the breast reduction outcome.
      Objective: This study was designed to evaluate the short and long-term effects of
      breast reduction from the perspective of BMI and BRA. Methods: One hundred fifty
      seven consecutive patients were invited to participate in the study. All clinical
      information was recorded on a breast surgery form. Patients completed a
      standardized questionnaire preoperatively, at postoperative year 1, and after
      postoperative year 5. Patients were grouped according to their BMI as "normal
      weight" and "overweight" and according to BRA as "minor/moderate reductions" and
      "major reductions." The differences in the BMI values and the life scores were
      compared between the BMI and BRA groups. Results: Sixty-four patients were
      included in the study. Postoperative year 1 BMIs were significantly lower than
      both the preoperative BMIs and postoperative year 5+ BMIs. The year 1 BMI
      decrease in the major reduction group was higher than the decrease in the
      minor/moderate reduction group. The postoperative life scores of all subgroups
      were better than the preoperative life scores. Conclusions: Reduction mammaplasty
      has a significant effect on short-term weight loss and the improvement in
      lifestyle. Patients tend to return to their original body weight in the long
      term. BRA is a significant variable in short-term weight loss, but neither BMI
      nor BRA has any other significant effect on the outcome in any time section.
      Level of Evidence: 4.

PMID- 29044365
TI  - Making Fat Transfer to Buttocks Safer.

PMID- 29044366
TI  - Sustainable food systems for optimal planetary health.
AB  - Sustainable food systems are an important component of a planetary health
      strategy to reduce the threat of infectious disease, minimize environmental
      footprint and promote nutrition. Human population trends and dietary transition
      have led to growing demand for food and increasing production and consumption of
      meat, amid declining availability of arable land and water. The intensification
      of livestock production has serious environmental and infectious disease impacts.
      Land clearing for agriculture alters ecosystems, increases human-wildlife
      interactions and leads to disease proliferation. Context-specific interventions
      should be evaluated towards optimizing nutrition resilience, minimizing
      environmental footprint and reducing animal and human disease risk.

PMID- 29044367
TI  - One Health Economics to confront disease threats.
AB  - Global economic impacts of epidemics suggest high return on investment in
      prevention and One Health capacity. However, such investments remain limited,
      contributing to persistent endemic diseases and vulnerability to emerging ones.
      An interdisciplinary workshop explored methods for country-level analysis of
      added value of One Health approaches to disease control. Key recommendations
      include: 1. systems thinking to identify risks and mitigation options for
      decision-making under uncertainty; 2. multisectoral economic impact assessment to
      identify wider relevance and possible resource-sharing, and 3. consistent
      integration of environmental considerations. Economic analysis offers a congruent
      measure of value complementing diverse impact metrics among sectors and contexts.

PMID- 29044368
TI  - Use of Bayesian networks in predicting contamination of drinking water with E.
      coli in rural Vietnam.
AB  - Background: More than 70 million Vietnamese rely on small-scale farming for some
      form of household income. Water on many of those farms is contaminated with
      waste, including animal manure, partly due to non-sustainable waste management.
      This increases the risk of water-related zoonotic disease transmission. The
      purpose of this research was to examine the impact of various demographic and
      management factors on the likelihood of finding Escherichia coli in drinking
      water sourced from wells and rainwater on farms in Vietnam. Methods: A Bayesian
      Belief Network (BBN) was designed to describe association between various
      deterministic and probabilistic variables gathered from 600 small-scale
      integrated (SSI) farmers in Vietnam. The variables relate to E. coli content of
      their drinking water sourced on-farm from wells and rainwater, and stored in on
      farm large vessels, including concrete water tanks. The BBN was developed using
      the Netica software tool; the model was calibrated and goodness of fit examined
      using concordance of predictability. Results: Sensitivity analysis of the model
      revealed that choice variables, including engagement in mitigation of water
      contamination and livestock management activities, were particularly likely to
      influence endpoint values, reflecting the highly variable and impactful nature of
      preferences, attitudes and beliefs relating to mitigation strategies.
      Quantitative variables including numbers of livestock (particularly chickens) and
      income also had a high impact. The highest concordance (62%) was achieved with
      the BBN reported in this paper. Conclusions: This BBN model of SSI farming in
      Vietnam is helpful in understanding the complexity of small-scale agriculture and
      how various factors work in concert to influence contamination of on-farm
      drinking water as indicated by the presence of E. coli. The model will also be
      useful for identifying and estimating the impact of policy options such as
      improved delivery of clean water management training for rural areas,
      particularly where such analysis is combined with other analytical and policy
      tools. With appropriate knowledge translation, the model results will be
      particularly useful in helping SSI farmers understand their options for engaging
      in public health mitigation strategies addressing clean water that do not
      significantly disrupt their agriculture-based livelihoods.

PMID- 29044369
TI  - Law as a fixture between the One Health interfaces of emerging diseases.
AB  - A One Health approach calls for multisectoral and multi-institutional cooperation
      and partnership across the interfaces of human, animal and ecosystem health
      risks. Without strong governance, these interfaces risk detaching, leaving gaps
      in capacities to prevent, detect and respond to emerging and persisting public
      health threats. As a crucial component of governance, law can act as the fixture
      between interfaces. We examine some of the many forms and foci of law and propose
      that the process of law-making, implementation and evaluation can provide a
      benefit for strengthening law as a fixture between One Health interfaces. To
      demonstrate this, we discuss three current examples of international legal
      instruments for emerging infectious diseases: the International Health
      Regulations, the Pandemic Influenza Preparedness Framework and the Global Action
      Plan on Antimicrobial Resistance.

PMID- 29044370
TI  - The ecology and epidemiology of Ross River and Murray Valley encephalitis viruses
      in Western Australia: examples of One Health in Action.
AB  - Arboviruses are maintained and transmitted through an alternating biological
      cycle in arthropods and vertebrates, with largely incidental disease in humans
      and animals. As such, they provide excellent examples of One Health, as their
      health impact is inextricably linked to their vertebrate hosts, their arthropod
      vectors and the environment. Prevention and control requires a comprehensive
      understanding of these interactions, and how they may be effectively and safely
      modified. This review concentrates on human disease due to Ross River and Murray
      Valley encephalitis viruses, the two major arboviral pathogens in Australia. It
      describes how their pattern of infection and disease is influenced by natural
      climatic and weather patterns, and by anthropogenic activities. The latter
      includes human-mediated environmental manipulations, such as water impoundment
      infrastructures, human movements and migration, and community and social changes,
      such as urban spread into mosquito larval habitats. Effective interventions need
      to be directed at the environmental precursors of risk. This can best be achieved
      using One Health approaches to improve collaboration and coordination between
      different disciplines and cross-sectoral jurisdictions in order to develop more
      holistic mitigation and control procedures, and to address poorly understood
      ecological issues through multidisciplinary research.

PMID- 29044371
TI  - Nosocomial amplification of MERS-coronavirus in South Korea, 2015.
AB  - Background: Nosocomial amplification resulted in nearly 200 cases of Middle East
      respiratory syndrome (MERS) during the 2015 South Korean MERS-coronavirus
      outbreak. It remains unclear whether certain types of cases were more likely to
      cause secondary infections than others, and if so, why. Methods: Publicly
      available demographic and transmission network data for all cases were collected
      from the Ministry of Health and Welfare. Statistical analyses were conducted to
      determine the relationship between demographic characteristics and the likelihood
      of human-to-human transmission. Findings from the statistical analyses were used
      to inform a hypothesis-directed literature review, through which mechanistic
      explanations for nosocomial amplification were developed. Results: Cases that
      failed to recover from MERS were more likely to cause secondary infections than
      those that did. Increased probability of direct, human-to-human transmission due
      to clinical manifestations associated with death, as well as indirect
      transmission via environmental contamination (e.g., fomites and indoor
      ventilation systems), may serve as mechanistic explanations for nosocomial
      amplification of MERS-coronavirus in South Korea. Conclusions: In addition to
      closely monitoring contacts of MERS cases that fail to recover during future
      nosocomial outbreaks, potential fomites with which they may have had contact
      should be sanitized. Furthermore, indoor ventilation systems that minimize
      recirculation of pathogen-bearing droplets should be implemented whenever
      possible.

PMID- 29044372
TI  - Should we be treating animal schistosomiasis in Africa? The need for a One Health
      economic evaluation of schistosomiasis control in people and their livestock.
AB  - A One Health economic perspective allows informed decisions to be made regarding
      control priorities and/or implementation strategies for infectious diseases.
      Schistosomiasis is a major and highly resilient disease of both humans and
      livestock. The zoonotic component of transmission in sub-Saharan Africa appears
      to be more significant than previously assumed, and may thereby affect the
      recently revised WHO vision to eliminate schistosomiasis as a public health
      problem by 2025. Moreover, animal schistosomiasis is likely to be a significant
      cost to affected communities due to its direct and indirect impact on
      livelihoods. We argue here for a comprehensive evaluation of the economic burden
      of livestock and zoonotic schistosomiasis in sub-Saharan Africa in order to
      determine if extending treatment to include animal hosts in a One Health approach
      is economically, as well as epidemiologically, desirable.

PMID- 29044373
TI  - Antimicrobial resistance: a One Health perspective.
AB  - Introduction: Worsening antimicrobial resistance (AMR) threatens the practice of
      modern human and veterinary medicine. For decades, medicine and agriculture have
      blamed each other for the rise of resistant microbes. Widespread use and misuse
      of antibiotics in both medicine and agriculture have increased the prevalence and
      expression of resistance genes. VRE: The rise of vancomycin-resistant
      Enterococcus faecium (VRE) in the European Union (EU) led to the ban of
      avoparcin, an antibiotic that is chemically related to vancomycin. In the years
      post-ban, VRE surveillance data of EU hospitals showed no obvious reduction in
      VRE rates. The USA never approved avoparcin, yet VRE has been an enormous problem
      in its hospitals. AMR surveillance data showed zero rates of VRE in US livestock.
      Whole-genome sequencing data suggest that VRE might have evolved from ampicillin
      resistant E. faecium from dogs. Companion animals have been completely ignored in
      the AMR debate. Sanitation: In addition, 1 billion people openly defecate around
      the world. Of these, 60% live in India, a country with highly resistant microbes.
      Conclusion: A One Health approach integrating human, animal and environmental
      whole-genome sequencing surveillance data is essential to getting to the root of
      AMR and developing effective prevention and control strategies.

PMID- 29044374
TI  - Human and livestock trematode infections in a mobile pastoralist setting at Lake
      Chad: added value of a One Health approach beyond zoonotic diseases research.
AB  - Background: At Lake Chad in Central Africa, mobile pastoralists face economic
      losses due to livestock trematodiases. Fasciola gigantica and Schistosoma bovis
      trematodes that affect livestock-share transmission ecology traits with
      Schistosoma haematobium and S. mansoni that cause human schistosomiasis. This
      project aimed at assessing treatment strategies and elucidating the predictive
      potential of human and livestock trematode infections. Methods: Schistosomiasis
      and fascioliasis were investigated concurrently in humans and cattle by repeated
      cross-sectional surveys. Urine and stool samples from humans and faecal samples
      from cattle were examined for trematode eggs. Treatment strategies were assessed
      by means of focus group discussions and in-depth interviews. Results: Mobile
      pastoralists of four ethnic groups participated. Prevalence of human
      schistosomiasis and livestock trematodiases showed considerable heterogeneity
      from one ethnic group to another, but correlated within ethnic groups. Effective
      trematocidal drugs were not available in the study area. Conclusions: Mutual
      predictive potential of human schistosomiasis and livestock fascioliasis relates
      to distinct livestock husbandry practices. Introducing efficacious strategic
      treatment against human schistosomiasis and livestock fascioliasis might improve
      human and animal health and well-being. Our research provides evidence for the
      benefits of a One Health approach targeting diseases that share specific
      ecological traits.

PMID- 29044375
TI  - The One Health path to infectious disease prevention and resilience.

PMID- 29044376
TI  - Pectobacterium atrosepticum exopolysaccharides: identification, molecular
      structure, formation under stress and in planta conditions.
AB  - In the present study, we identified exopolysaccharides of the harmful
      phytopathogenic bacterium Pectobacterium atrosepticum SCRI1043 and characterized
      the molecular structure of these polymers. The synthesis of the target
      polysaccharides was shown to be induced under starvation conditions. Moreover,
      intensive accumulation of exopolysaccharides occurred during the colonization by
      bacteria of the xylem vessels of infected plants, where microorganisms formed
      specific 3D "multicellular" structures-bacterial emboli. Thus, the identified
      polymers are likely to be involved in the adaptation and virulence of bacteria of
      Pectobacterium genus.

PMID- 29044378
TI  - Glyco-Forum.

PMID- 29044377
TI  - Heparosan-coated liposomes for drug delivery.
AB  - Liposomal encapsulation is a useful drug delivery strategy for small molecules,
      especially chemotherapeutic agents such as doxorubicin. Doxil(r) is a doxorubicin
      containing liposome ("dox-liposome") that passively targets drug to tumors while
      reducing side effects caused by free drug permeating and poisoning healthy
      tissues. Polyethylene glycol (PEG) is the hydrophilic coating of Doxil(r) that
      protects the formulation from triggering the mononuclear phagocyte system (MPS).
      Evading the MPS prolongs dox-liposome circulation time thus increasing drug
      deposition at the tumor site. However, multiple doses of Doxil(r) sometimes
      activate an anti-PEG immune response that enhances liposome clearance from
      circulation and causes hypersensitivity, further limiting its effectiveness
      against disease. These side effects constrain the utility of PEG-coated liposomes
      in certain populations, justifying the need for investigation into alternative
      coatings that could improve drug delivery for better patient quality of life and
      outcome. We hypothesized that heparosan (HEP; [-4-GlcA-beta1-4-GlcNAc-alpha1-]n)
      may serve as a PEG alternative for coating liposomes. HEP is a natural precursor
      to heparin biosynthesis in mammals. Also, bacteria expressing an HEP
      extracellular capsule during infection escape detection and are recognized as
      "self," not a foreign threat. By analogy, coating drug-carrying liposomes with
      HEP should camouflage the delivery vehicle from the MPS, extending circulation
      time and potentially avoiding immune-mediated clearance. In this study, we
      characterize the postmodification insertion of HEP-lipids into liposomes by
      dynamic light scattering and coarse-grain computer modeling, test HEP-lipid
      immunogenicity in rats, and compare the efficacy of drug delivered by HEP-coated
      liposomes to PEG-coated liposomes in a human breast cancer xenograft mouse model.

PMID- 29044379
TI  - The Important Role of Community Engagement and Social Capital in Child Health
      Systems.

PMID- 29044381
TI  - Double trouble for transcatheter aortic valve implantation: a patient with no
      vascular access and high-risk features for bilateral coronary obstruction.

PMID- 29044382
TI  - SOURCE 3 at 1 year: what can we learn?

PMID- 29044383
TI  - The European Society of Cardiology Clinical Practice Guidelines.

PMID- 29044385
TI  - The 'Ten Commandments' in Valvular Heart Disease Guidelines.

PMID- 29044384
TI  - ESC Clinical Practice Guidelines on the Management of Valvular Heart Disease-2017
      Update.

PMID- 29044386
TI  - Valve Thrombosis after TAVI.

PMID- 29044387
TI  - Leaflet Thrombosis after TAVI.

PMID- 29044388
TI  - The Future of TAVI.

PMID- 29044389
TI  - Novel Technologies for percutaneous treatment of tricuspid valve regurgitation.

PMID- 29044390
TI  - Regenerative transcatheter valves.

PMID- 29044391
TI  - Role and function of extracellular vesicles in calcific aortic valve disease.

PMID- 29044392
TI  - From Cinderella to centre stage: valvular heart disease on the move.

PMID- 29044393
TI  - Duration of dual antiplatelet therapy and associated outcomes following
      percutaneous coronary intervention for acute myocardial infarction: contemporary
      practice insights from the Canadian Observational Antiplatelet Study.
AB  - Aims: There is a paucity of real-world, contemporary data of practice patterns
      and clinical outcomes following dual-antiplatelet therapy (DAPT) in acute
      myocardial infarction (AMI) patients treated with percutaneous coronary
      intervention (PCI). Methods and results: The Canadian Observational Antiplatelet
      Study was a prospective, multicentre, cohort study examining adenosine
      diphosphate receptor antagonist use following PCI for AMI. We compared practice
      patterns, patient characteristics, and clinical outcomes in relation to DAPT
      duration (<6 weeks, 6 weeks to <6 months, 6 to <12, and >=12 months). The primary
      outcome was the composite of non-fatal AMI, unplanned coronary revascularization,
      stent thrombosis, new or worsening heart failure, cardiogenic shock, or stroke.
      We identified 2034 patients with AMI treated with PCI. DAPT duration was <6 weeks
      in 5.2% of patients; 6 weeks to <6 months in 7.0%; 6 to <12 months in 12.6%; and
      >=12 months in 75.3%. Patients who discontinued DAPT early had higher GRACE risk
      scores. Overall, mortality rate at 15 months was 2.5%. Compared with a duration
      of DAPT of >=12 months, discontinuation of DAPT <6 weeks (P < 0.0001) and 6 weeks
      to <6 months (P = 0.02), but not 6 months to <12 months (P = 0.06), were
      independently associated with a higher incidence of the primary outcome among
      survivors. Conclusion: One-in-four patients with AMI treated with PCI
      discontinued DAPT prior to the guideline-recommended 12-month duration. Patients
      in whom DAPT was discontinued early were at higher baseline risk and had higher
      rates of non-fatal ischaemic events during follow up.

PMID- 29044394
TI  - Prediction of cardiovascular risk in patients with familial
      hypercholesterolaemia.
AB  - Aims: Patients with familial hypercholesterolaemia (FH) have an elevated
      cardiovascular (CV) risk. The objective of this analysis was to adjust CV risk
      equations derived in non-FH populations with hyperlipidaemia to predict CV risk
      in FH patients, and then to use these adjusted CV risk equations in a decision
      analytic model in order to predict lifetime CV risk in FH patients. Methods and
      results: A literature search of publications reporting CV risk in FH patients
      identified the publication with the most credible estimate of CV risk increase. A
      CV event rate ratio (RR) (FH vs. non-FH) was derived from reported odds ratios by
      pooling treated and untreated patients. Predicted CV event risks based on non-FH
      risk equations were adjusted with the RR to reflect CV risk in FH patients. A
      decision analytic model incorporating these adjusted risk equations was used to
      predict 10-year and lifetime CV risk in FH patients. Combining the derived RR of
      7.1 (95% CI: 5.7-8.7) with the predicted CV risks in a decision analytic model
      yielded 10-year and lifetime risk estimates of 45% and 88% in FH patients based
      on the RUTHERFORD-2 trial population. Based on the initial (cross-sectional) RR
      of 7.1, FH patients were predicted to have 3.9 times more events over their
      lifetime than non-FH patients with a similar risk profile. Conclusion: The CV
      risk in FH is high and represents an unmet medical need for patients. Increased
      efforts for better diagnosis and management of FH should be employed to improve
      patient outcomes.

PMID- 29044395
TI  - Modelling total coronary heart disease burden and long-term benefit of
      cholesterol lowering in middle aged men with and without a history of
      cardiovascular disease.
AB  - Aims: Cumulative coronary heart disease (CHD) events over 20 years were examined
      in men screened for, and in those randomized to, the West of Scotland Coronary
      Prevention Study. Methods and results: Record linkage provided CHD-related events
      and days in hospital for the 80 230 screenees, including the randomized cohort of
      6595 men. Risk factors were determined at baseline, and disease burden assessed
      for groups defined by cholesterol. Effects of cholesterol lowering were modelled
      from differences between groups, and from the treatment arms of the trial. Over
      20 years, those without a history of CHD (n = 61 211) had 23.0 events per 100
      subjects in the lowest cholesterol group (mean 4.0 mmol/L) and 65.1 per 100 in
      the highest (8.8 mmol/L). Corresponding days in hospital were 167.2-435.4 per 100
      subjects. Analogous figures for men with a CHD history (n = 8570) were 77.3-141.7
      events per 100 and 526.1-936.7 hospital days per 100. Lowering cholesterol by
      about 1.0 mmol/L in men with average cholesterol and no CHD was predicted to be
      associated with 8.9 fewer events and a saving of 56.0 hospital days per 100. In
      those with CHD this difference gave, depending on starting level, 26.8-36.5 fewer
      events and savings of 158.2-247.3 hospital days per 100 subjects. Comparison of
      cumulative events in 45-54 vs. 55-64 year olds in the trial revealed greater
      benefit from intervention in the younger decade. Conclusion: Long-term,
      longitudinal data reveal the considerable CHD burden in middle-aged men and
      indicate substantial clinical benefits from both moderate and aggressive
      cholesterol lowering.

PMID- 29044396
TI  - Systematic review and meta-analysis to compare outcomes between intermediate- and
      high-risk patients undergoing transcatheter aortic valve implantation.
AB  - Aims: Recent studies have reported non-inferior outcomes for transcatheter aortic
      valve implantation (TAVI) compared with surgical aortic valve replacement (SAVR)
      in intermediate-risk patients. However, a comparison of outcomes among TAVI
      patients depending upon the surgical risk score has not been performed in a large
      study. Our aim was to compare the outcomes of TAVI in low-, intermediate-, and
      high-risk patients, to ascertain if the morbidity and mortality is related to the
      patient's risk profile or the procedure itself. Methods and results: A thorough
      computer-based search was performed using Ovid MEDLINE, EMBASE, Google Scholar,
      and PubMed databases. We included original research studies reporting data on
      TAVI in the low-, intermediate-, and high-risk groups. Patients in intermediate
      risk group were compared to the high-risk cohort for device success, mortality,
      and complications. A total of 2414 patients in the intermediate-risk group were
      compared with 1597 high-risk patients. On meta-analysis, intermediate-risk group
      demonstrated similar device success [odds ratio (OR) 1.29, 95% confidence
      interval (CI) 0.87-1.90, I2 = 0%, P = 0.2) but a lower 30-day mortality OR 0.54,
      95% CI 0.34-0.86, I2 = 49%, P = 0.009). There was no difference in the incidence
      of stroke (OR 1.17, 95% CI 0.80-1.71, I2 = 36%, P = 0.42) or permanent pacemaker
      implantation between the two groups (OR 1.04, 95% CI 0.82-1.32, I2 = 41%, P =
      0.74). Conclusion: Transcatheter aortic valve implantation in intermediate-risk
      patients carries a low mortality and high success. Incidence of pacemaker and
      stroke remains high in the lower risk group.

PMID- 29044397
TI  - Depression in patients with coronary artery disease: a more significant problem
      than previously recognized?

PMID- 29044398
TI  - Trends in mortality and major complications for patients undergoing coronary
      artery bypass grafting among Urban Teaching Hospitals in China: 2004 to 2013.
AB  - Aims: Although the number of hospitals performing cardiac surgery has increased
      rapidly in China, information regarding the trends in coronary artery bypass
      grafting (CABG) outcomes remains unknown. Methods and results: We used data from
      the Chinese Cardiac Surgery Registry, the largest registry system that accounts
      for nearly 50% of total annual CABG volume in China, to assess trends of in
      hospital mortality and major complication rates for patients receiving isolated
      CABG in 102 urban teaching hospitals in China from 25 January 2004 through 31
      December 2013 (except 2006 and 2009). Using a mixed effects model, we estimated
      annual trends in each of these two outcomes overall and by age groups (18-64 and
      65 years or older), adjusted for patient characteristics. We also assessed the
      trends in pre-operative, post-operative, and total length of stay (LOS). The
      study included 40 652 patients across 102 hospitals. Between 2004 and 2013,
      patients' mean age decreased from 62.7 to 61.4 years, in-hospital mortality
      decreased from 2.8% to 1.6% (difference, 1.3%, 95% CI: 0.70-1.85), and major
      complication rates decreased from 7.8% to 3.8% (difference, 4.0%; 95% CI: 3.05
      4.90). The reduction in mortality and major complication rates were consistent
      across age groups. Between 2004 and 2013, the median (inter-quartile range) pre
      operative LOS remained unchanged, post-operative LOS declined from 12.0 (8.0) to
      10.0 (7.0) days, and total LOS declined from 22.0 (13.0) to 20.0 (12.0) days.
      Conclusion: Isolated CABG-related in-hospital mortality, major complication
      rates, and LOS have improved in urban teaching hospitals in China over the last
      decade.

PMID- 29044399
TI  - Barriers and facilitators to public access defibrillation in out-of-hospital
      cardiac arrest: a systematic review.
AB  - Public access defibrillation initiatives make automated external defibrillators
      available to the public. This facilitates earlier defibrillation of out-of
      hospital cardiac arrest victims and could save many lives. It is currently only
      used for a minority of cases. The aim of this systematic review was to identify
      barriers and facilitators to public access defibrillation. A comprehensive
      literature review was undertaken defining formal search terms for a systematic
      review of the literature in March 2017. Studies were included if they considered
      reasons affecting the likelihood of public access defibrillation and presented
      original data. An electronic search strategy was devised searching MEDLINE and
      EMBASE, supplemented by bibliography and related-article searches. Given the low
      quality and observational nature of the majority of articles, a narrative review
      was performed. Sixty-four articles were identified in the initial literature
      search. An additional four unique articles were identified from the electronic
      search strategies. The following themes were identified related to public access
      defibrillation: knowledge and awareness; willingness to use; acquisition and
      maintenance; availability and accessibility; training issues; registration and
      regulation; medicolegal issues; emergency medical services dispatch-assisted use
      of automated external defibrillators; automated external defibrillator-locator
      systems; demographic factors; other behavioural factors. In conclusion, several
      barriers and facilitators to public access defibrillation deployment were
      identified. However, the evidence is of very low quality and there is not enough
      information to inform changes in practice. This is an area in urgent need of
      further high-quality research if public access defibrillation is to be increased
      and more lives saved. PROSPERO registration number CRD42016035543.

PMID- 29044400
TI  - Erratum.

PMID- 29044401
TI  - Shifting transcatheter aortic valve implantation to low-risk patients: a
      pilgrimage with no shortcuts.

PMID- 29044402
TI  - Yersinia enterocolitica CsrA regulates expression of the Ysa and Ysc type 3
      secretion system in unique ways.
AB  - This study investigated how carbon storage regulator A (CsrA) affects expression
      of the Ysa and Ysc type 3 secretion (T3S) system genetic regulatory cascades that
      control Ysps (Yersinia secreted proteins) and Yops (Yersinia outer proteins)
      export, respectively. Given that most often CsrA acts as a mediator of mRNA
      stability, an activity that can be monitored using lacZ transcriptional fusions,
      we employed a collection of reporter strains to assess Ysa and Ysc gene
      expression. To this end, bacteria were cultivated to induce either the Ysa or the
      Ysc T3S system. Comparison of csrA mutants to the wild-type strain revealed that,
      in response to the respective inducing conditions, genes spanning the Ysa and Ysc
      gene cascades displayed increased expressions. Then, the possibility that CsrA
      affects secretion of Ysps and Yops was tested and the profiles of secreted
      proteins by wild-type and csrA mutant strains were compared by proteomic
      analysis. Ysps were over-secreted and Yops were under-secreted, for the csrA
      mutant. These results support the hypothesis that CsrA affects both the Ysa and
      Ysc T3S systems in Yersinia enterocolitica. They further support the conclusion
      that CsrA plays an important role in controlling adaptation of this pathogenic
      bacterium during its lifecycle shift between a terrestrial and parasitic
      existence.

PMID- 29044403
TI  - Involvement of formate dehydrogenases in stationary phase oxidative stress
      tolerance in Escherichia coli.
AB  - Previously, we constructed a series of reduced-genome strains of Escherichia coli
      by combining large-scale chromosome deletions and then tested the sensitivity of
      these strains to the redox-cycling drug menadione. In this study, we analyzed a
      deletion that increased menadione sensitivity and discovered that loss of
      selenocysteine synthase genes was responsible for the strain's reduced tolerance
      to oxidative stress. Mutants of formate dehydrogenases, which are selenocysteine
      containing enzymes, were also sensitive to menadione, indicating that these
      enzymes are involved in oxidative stress during stationary phase, specifically
      under microaerobic conditions in the presence of glucose. Among three formate
      dehydrogenases encoded by the E. coli genome, two were responsible for the
      observed phenotypes: formate dehydrogenase-H and -O. In a mutant of fdhD, which
      encodes a sulfur transferase that is essential for formate dehydrogenase
      activity, formate dehydrogenase-O could still contribute to oxidative stress
      tolerance, revealing a novel role for this protein. Consistent with this,
      overproduction of the electron transfer subunits of this enzyme, FdoH and FdoI,
      increased menadione tolerance and supported survival in stationary phase. These
      results suggested that formate dehydrogenase-O serves as an electron transfer
      element in glucose metabolism to promote oxidative stress tolerance and survival
      in stationary phase.

PMID- 29044404
TI  - A new cordycepin-producing caterpillar fungus Ophiocordyceps xuefengensis with
      artificial infection to the host, cultivation of mycelia and stromata.
AB  - Caterpillar fungi have numerous pharmacological and therapeutic applications in
      traditional medicine, due to a variety of active chemical constituents, such as
      cordycepin and adenosine. It is imperative to discover new resource for
      artificial cultivation and biometabolite production since the traditional natural
      species are endangered. In this study, a new strain HACM 001 was isolated and
      identified as Ophiocordyceps xuefengensis by rDNA-ITS sequencing. This strain
      showed the potential of artificial infection to caterpillar larvae leading to
      mummification, as well as fermentation mycelia in liquid culture and cultivation
      stromata in solid medium. Eight nucleosides and nucleobases, especially
      cordycepin and adenosine, were determined and analyzed with HPLC-DAD-Q-TOF-MS/MS
      technology. Cordycepin was detected in all forms of present O. xuefengensis
      strain at different contents, among which the highest content (37.1 MUg/g)
      appeared in the stromata cultivated on solid medium. The content of adenosine in
      mycelia and stromata, respectively, reached 1155 MUg/g and 1470 MUg/g. Therefore,
      O. xuefengensis might be an alternative source for obtaining artificial fungus
      caterpillar-larvae complex and producing cordycepin and adenosine.

PMID- 29044407
TI  - CORRIGENDUM FOR "1,5-Anhydroglucitol in Saliva Is a Noninvasive Marker of Short
      Term Glycemic Control".

PMID- 29044406
TI  - Clinical Mycobacterium abscessus strain inhibits autophagy flux and promotes its
      growth in murine macrophages.
AB  - Autophagy is known to be a vital homeostatic defense process that controls
      mycobacterial infection. However, the relationship between autophagy response and
      the virulence of Mycobacterium abscessus strain UC22 has not been reported. Here,
      we demonstrate that M. abscessus induces autophagy and inhibits autophagy flux in
      murine macrophages. Further, the rough variant of M. abscessus, UC22 that is a
      highly virulent clinical isolate, significantly inhibited autophagic flux than
      the smooth variant of M. abscessus ATCC 19977. In addition, it was noticed that
      the intracellular survival of UC22 is significantly enhanced by blocking the
      autophagosome-lysosome fusion in macrophages compared to the smooth variant.
      However, Mycobacterium smegmatis did not block autophagy flux in murine
      macrophages. Besides, we confirmed that the lipid components of M. abscessus UC22
      play a role in autophagosome formation. These data suggest that the virulent M.
      abscessus might be able to survive and grow within autophagosomes by preventing
      the autophagosome-lysosome fusion and their clearance from the cells.

PMID- 29044408
TI  - Testing a Positive Psychological Intervention for Osteoarthritis.
AB  - Objective: Osteoarthritis is a leading cause of disability for which there is no
      cure. Psychosocial-oriented treatments are underexplored. We developed and tested
      an intervention to build positive psychological skills (e.g., gratitude) to
      reduce osteoarthritis symptom severity, including pain and functioning, and to
      improve psychosocial well-being in patients with knee or hip osteoarthritis.
      Design: Two-arm randomized design with six-month follow-up. Setting: An academic
      Veterans Affairs Medical Center. Subjects: Patients aged 50 years or older with
      knee or hip osteoarthritis and pain ratings of 4 or higher. Methods: Patients (N
      = 42) were randomized to a six-week program containing positive skill-building
      activities or neutral control activities tailored to the patient population.
      Adherence was assessed by telephone each week. We assessed osteoarthritis symptom
      severity (WOMAC Osteoarthritis Index) and measures of well-being (positive
      affect, negative affect, and life satisfaction) at baseline and by telephone one,
      three, and six months after the program ended. We used linear mixed models to
      examine changes over time. Results: The majority (64%) of patients completed more
      than 80% of their weekly activities. Patients in the positive (vs neutral)
      program reported significantly more improvement over time in osteoarthritis
      symptom severity (P = 0.02, Cohen's d = 0.86), negative affect (P = 0.03, Cohen's
      d = 0.50), and life satisfaction (P = 0.02, Cohen's d = 0.36). Conclusions: The
      study successfully engaged patients with knee or hip osteoarthritis in a six-week
      intervention to build positive psychological skills. Improving osteoarthritis
      symptom severity and measures of psychosocial well-being, the intervention shows
      promise as a tool for chronic pain management.

PMID- 29044409
TI  - Improving Pain Care with Project ECHO in Community Health Centers.
AB  - Objective: Pain is an extremely common complaint in primary care, and patient
      outcomes are often suboptimal. This project evaluated the impact of Project ECHO
      Pain videoconference case-based learning sessions on knowledge and quality of
      pain care in two Federally Qualified Health Centers. Design: Quasi-experimental,
      pre-post intervention, with comparison group. Setting: Two large, multisite
      federally qualified health centers in Connecticut and Arizona. Subjects:
      Intervention (N = 10) and comparison (N = 10) primary care providers. Methods:
      Primary care providers attended 48 weekly Project ECHO Pain sessions between
      January and December 2013, led by a multidisciplinary pain specialty team.
      Surveys and focus groups assessed providers' pain-related knowledge and self
      efficacy. Electronic health record data were analyzed to evaluate opioid
      prescribing and specialty referrals. Results: Compared with control, primary care
      providers in the intervention had a significantly greater increase in pain
      related knowledge and self-efficacy. Providers who attended ECHO were more likely
      to use formal assessment tools and opioid agreements and refer to behavioral
      health and physical therapy compared with control providers. Opioid prescribing
      decreased significantly more among providers in the intervention compared with
      those in the control group. Conclusions: Pain is an extremely common and
      challenging problem, particularly among vulnerable patients such as those cared
      for at the more than 1,200 Federally Qualified Health Centers in the United
      States. In this study, attendance at weekly Project ECHO Pain sessions not only
      improved knowledge and self-efficacy, but also altered prescribing and referral
      patterns, suggesting that knowledge acquired during ECHO sessions translated into
      practice changes.

PMID- 29044411
TI  - National Academies of Sciences, Engineering, and Medicine (NASEM).

PMID- 29044410
TI  - The Power of Pain Education: a Call for Robust Research.

PMID- 29044412
TI  - Correlation Between Extravasation and Alterations of Cerebrovascular Laminin and
      beta-Dystroglycan Immunoreactivity Following Cryogenic Lesions in Rats.
AB  - The blood-brain barrier becomes "leaky" following lesions. Former studies
      revealed that following lesions the immunoreactivity of cerebrovascular laminin
      becomes detectable whereas that of beta-dystroglycan disappears. These
      alterations may be indicators of glio-vascular decoupling that may result in the
      impairment of the blood-brain-barrier. This study investigates correlation
      between the post-lesion extravasation and the above-mentioned immunohistochemical
      alterations. Following cryogenic lesions, the survival periods lasted 5, 10, 30
      minutes, 1 or 12 hours, or 1 day. Some brains were fixed immediately post-lesion.
      Immunofluorescent reactions were performed in floating sections. The
      extravasation was detected with immunostaining for plasma fibronectin and rat
      immunoglobulins. When the survival period was 30 minutes or longer, the area of
      extravasation corresponded to the area of altered laminin and beta-dystroglycan
      immunoreactivities. Following immediate fixation some laminin immunoreactivity
      was already detected. The extravasation seemed to precede this early appearance
      of laminin immunoreactivity. The beta-dystroglycan immunoreactivity disappeared
      later. When the extravasation spread into the corpus callosum, vascular laminin
      immunoreactivity appeared but the beta-dystroglycan immunoreactivity persisted.
      It seems that extravasation separates the glial and vascular basal laminae, which
      results in the appearance of laminin immunoreactivity. The disappearance of beta
      dystroglycan immunoreactivity is neither a condition nor an inevitable
      consequence of the 2 other phenomena.

PMID- 29044413
TI  - A Different Understanding of Myelin: A Legacy.

PMID- 29044414
TI  - Polymer Coating Embolism: Cause of Cerebral Vasculopathy and Death following
      Congenital Heart Repair in Two Infants.

PMID- 29044415
TI  - Morphologic and Elemental Analysis of Primary Melanosis of the Dentate Nucleus:
      Review and Correlation With Neuromelanin.
AB  - Primary melanosis of the dentate nucleus is a rarely described entity with
      neither known cause nor definitive clinicopathologic correlation. We revisit this
      previously reported phenomenon by presenting one such case with a review of the
      pathology as well as additional investigations including elemental analysis by
      energy-dispersive X-ray, immunohistochemistry and electron microscopy. The lesion
      presented macroscopically as a sharply defined, black pigmentation that was
      restricted to the dentate nucleus of the cerebellum. Other deep nuclei were
      uninvolved. Similarly, other areas of the cerebellum, brainstem, and
      supratentorial regions were macroscopically free of pigment. Microscopically,
      however, the pigment was noted to be present, albeit in microscopic deposits,
      within layers of the cerebellar cortex. Additionally, immunohistochemistry and
      electron microscopy defined an intracellular component within astrocytes. X-ray
      analysis of the pigment showed it to consist almost entirely of sulfur, an
      element known to be prominent in neuromelanin. This report also describes an
      association of the pigment with astrocytes by ultrastructural examination. We
      discuss the results of our findings in the context of etiopathogenetic
      considerations, seeking to gain a better understanding of this abnormal
      pigmentation and its relationship to neuromelanin.

PMID- 29044416
TI  - Disease and Region Specificity of Granulin Immunopositivities in Alzheimer
      Disease and Frontotemporal Lobar Degeneration.
AB  - Heterozygous loss-of-function mutations in GRN, the progranulin gene, which
      result in progranulin (PGRN) protein haploinsufficiency, are a major cause of
      frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). PGRN is
      composed of seven and a half repeats of a highly conserved granulin motif that is
      cleaved to produce the granulin peptides A-G and paragranulin. To better
      understand the role of PGRN and granulin (Grn) peptides in the pathogenesis of
      neurodegeneration, we evaluated PGRN/Grn in brains of patients with Alzheimer
      disease, FTLD-TDP type A with or without GRN mutations, and normal individuals,
      using a panel of monoclonal antibodies against Grn peptides A-G. In the
      neocortex, Grn peptide-specific immunostains were observed, for example,
      membranous Grn E immunopositivity in pyramidal neurons, and Grn C
      immunopositivity in ramified microglia. In the hippocampus, Grn immunopositivity
      in the CA1 and CA2 regions showed disease-specific changes in both neurons and
      microglia. Most interestingly, in FTLD-TDP type A with GRN mutations, there is a
      60% decrease in the density of Grn-positive microglia in the hippocampal CA1,
      suggesting that haploinsufficiency of the GRN mutations also extends to PGRN
      expression in microglia. This study provides important insights into future
      studies of the pathogenesis and treatment of FTLD-TDP.

PMID- 29044417
TI  - Pathologic Correlation of Paramagnetic White Matter Lesions in Adult-Onset
      Leukoencephalopathy With Axonal Spheroids and Pigmented Glia.
AB  - It has been proposed that susceptibility-weighted imaging is a sensitive magnetic
      resonance imaging (MRI) technique for identifying white matter (WM) pathologic
      changes involving demyelination and iron accumulation. We identified the tree
      silhouette-like configuration with a paramagnetic phase shift in the frontal
      subcortical WM lesions of 4 patients with adult-onset leukoencephalopathy with
      axonal spheroids and pigmented glia who underwent 3T MRI. According to our
      postmortem 7T MRI and histologic correlation study to investigate the origin of
      the susceptibility-related phase contrast, changes in the subcortical WM
      architecture and central WM loss with the relative preservation of iron-rich U
      fibers may contribute to the paramagnetic susceptibility.

PMID- 29044418
TI  - Friedreich Ataxia: Developmental Failure of the Dorsal Root Entry Zone.
AB  - Dorsal root ganglia, dorsal roots (DR), and dorsal root entry zones (DREZ) are
      vulnerable to frataxin deficiency in Friedreich ataxia (FA). A previously
      unrecognized abnormality is the intrusion of astroglial tissue into DR. Segments
      of formalin-fixed upper lumbar spinal cord of 13 homozygous and 2 compound
      heterozygous FA patients were sectioned longitudinally to represent DREZ and
      stained for glial fibrillary acidic protein (GFAP), S100, vimentin, the central
      nervous system (CNS)-specific myelin protein proteolipid protein, the peripheral
      nervous system (PNS) myelin proteins PMP-22 and P0, and the Schwann cell proteins
      laminin, alpha-dystroglycan, and periaxin. Normal DREZ showed short, sharply
      demarcated, dome-like extensions of CNS tissue into DR. The Schwann cell-related
      proteins formed tight caps around these domes. In FA, GFAP-, S100-, and vimentin
      reactive CNS tissue extended across DREZ and into DR over much longer distances
      by breaching the CNS-PNS barrier. The transition between PNS and CNS myelin
      proteins was disorganized. During development, neural-crest derived boundary cap
      cells provide guidance to dorsal root ganglia axons growing into the dorsal
      spinal cord and at the same time block the inappropriate intrusion of CNS glia
      into DR. It is likely that frataxin is required during a critical period of
      permissive (axons) and nonpermissive (astroglia) border-control.

PMID- 29044419
TI  - MYC/BCL2 Co-Expression Is a Stronger Prognostic Factor Compared With the Cell-of
      Origin Classification in Primary CNS DLBCL.
AB  - Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a
      subtype of DLBCL with an unfavorable prognosis and a poor response to the
      treatment. As we know, DLBCL is stratified into germinal center B-cell (GCB)-like
      and activated B-cell (ABC)-like subtypes with different prognosis according to
      their gene-expression characteristics. In this study, we analyzed a case series
      of 77 patients with primary CNS DLBCL. A difference in prognosis of GCB-like and
      ABC-like subtypes was noticed, but no statistical significance was found.
      However, significant prognostic value of MYC/BCL2 co-expression was shown. The
      cases with MYC/BCL2 co-expression did not show any predominance of the 2 subtypes
      in our cases. Furthermore, patients with MYC/BCL2 co-expression had significantly
      worse overall survival for both cell of origin (COO) subtypes. We conjecture that
      MYC/BCL2 co-expression is associated with a poorer prognosis and is independent
      of COO classification. Moreover, the data suggest that MYC/BCL2 co-expression is
      superior to COO classification assessed by immunohistochemical analysis in
      patients with primary CNS DLBCL.

PMID- 29044420
TI  - Characterization of a novel role for the dynamin mechanoenzymes in the regulation
      of human sperm acrosomal exocytosis.
AB  - STUDY QUESTION: Does dynamin regulate human sperm acrosomal exocytosis? SUMMARY
      ANSWER: Our studies of dynamin localization and function have implicated this
      family of mechanoenzymes in the regulation of progesterone-induced acrosomal
      exocytosis in human spermatozoa. WHAT IS KNOWN ALREADY: Completion of an acrosome
      reaction is a prerequisite for successful fertilization in all studied mammalian
      species. It follows that failure to complete this unique exocytotic event
      represents a common aetiology in the defective spermatozoa of male infertility
      patients that have failed IVF in a clinical setting. Recent studies have
      implicated the dynamin family of mechanoenzymes as important regulators of the
      acrosome reaction in murine spermatozoa. The biological basis of this activity
      appears to rest with the ability of dynamin to polymerize around newly formed
      membrane vesicles and subsequently regulate the rate of fusion pore expansion. To
      date, however, the dynamin family of GTPases have not been studied in the
      spermatozoa of non-rodent species. Here, we have sought to examine the presence
      and functional significance of dynamin in human spermatozoa. STUDY DESIGN, SIZE,
      DURATION: Dynamin expression was characterized in the testis and spermatozoa of
      several healthy normozoospermic individuals. In addition, we assessed the
      influence of selective dynamin inhibition on the competence of human spermatozoa
      to undergo a progesterone-induced acrosome reaction. A minimum of five biological
      and technical replicates were performed to investigate both inter- and intra
      donor variability in dynamin expression and establish statistical significance in
      terms of the impact of dynamin inhibition. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The expression and the localization of dynamin in the human testis,
      epididymis and mature spermatozoa were determined through the application of
      immunofluorescence, immunoblotting and/or electron microscopy. Human semen
      samples were fractionated via density gradient centrifugation and the resultant
      populations of good and poor quality spermatozoa were induced to capacitate and
      acrosome react in the presence or absence of selective dynamin inhibitors. The
      acrosome integrity of live spermatozoa was subsequently assessed via the use of
      fluorescently conjugated Arachis hypogea lectin (PNA). The influence of dynamin
      phosphorylation and the regulatory kinase(s) responsible for this modification in
      human spermatozoa were also assessed via the use of in situ proximity ligation
      assays and pharmacological inhibition. In all experiments, >=100 spermatozoa were
      assessed/treatment group and all graphical data are presented as the mean values
      +/- SEM, with statistical significance being determined by ANOVA. MAIN RESULTS
      AND THE ROLE OF CHANCE: Dynamin 1 (DNM1) and DNM2, but not DNM3, were
      specifically localized to the acrosomal region of the head of human spermatozoa,
      an ideal position from which to regulate acrosomal exocytosis. In keeping with
      this notion, pharmacological inhibition of DNM1 and DNM2 was able to
      significantly suppress the rates of acrosomal exocytosis stimulated by
      progesterone. Furthermore, our comparison of dynamin expression in good and poor
      quality spermatozoa recovered from the same ejaculate, revealed a significant
      reduction in the amount of DNM2 in the latter subpopulation of cells. In
      contrast, DNM1 was detected at equivalent levels in both subpopulations of
      spermatozoa. Such findings are of potential significance given that the poor
      quality spermatozoa proved refractory to the induction of a progesterone
      stimulated acrosome reaction. In seeking to identify the regulatory influence of
      progesterone on DNM2 function, we were able to establish that the protein is a
      substrate for CDK1-dependent phosphorylation. The functional significance of DNM2
      phosphorylation was illustrated by the fact that pharmacological inhibition of
      CDK1 elicited a concomitant suppression of both DNM2-Ser764 phosphorylation and
      the overall rates of progesterone-induced acrosomal exocytosis. LARGE SCALE DATA:
      N/A. LIMITATIONS REASONS FOR CAUTION: This was an in vitro study performed mainly
      on ejaculated human spermatozoa. This experimental paradigm necessarily
      eliminates the physiological contributions of the female reproductive tract that
      would normally support capacitation and acrosomal responsiveness. WIDER
      IMPLICATIONS OF THE FINDINGS: This study identifies a novel causative link
      between dynamin activity and the ability of human spermatozoa to complete a
      progesterone-induced acrosome reaction. Such findings encourage a more detailed
      analysis of the contribution of dynamin dysregulation as an underlying aetiology
      in infertile males whose spermatozoa are unable to penetrate the zona pellucida.
      STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a National
      Health and Medical Research Council of Australia Project Grant (APP1103176)
      awarded to B.N. and E.A.M. The authors report no conflict of interest.

PMID- 29044421
TI  - Heterogeneous hCG and hMG commercial preparations result in different
      intracellular signalling but induce a similar long-term progesterone response in
      vitro.
AB  - STUDY QUESTION: Are four urinary hCG/menotropin (hMG) and one recombinant
      preparation characterized by different molecular features and do they mediate
      specific intracellular signaling and steroidogenesis? SUMMARY ANSWER: hCG and hMG
      preparations have heterogeneous compositions and mediate preparation-specific
      cell signaling and early steroidogenesis, although similar progesterone plateau
      levels are achieved in 24 h-treated human primary granulosa cells in vitro. WHAT
      IS KNOWN ALREADY: hCG is the pregnancy hormone marketed as a drug for ARTs to
      induce final oocyte maturation and ovulation, and to support FSH action. Several
      hCG formulations are commercially available, differing in source, purification
      methods and biochemical composition. STUDY DESIGN, SIZE, DURATION: Commercial hCG
      preparations for ART or research purposes were compared in vitro.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The different preparations were
      quantified by immunoassay with calibration against the hCG standard (Fifth IS;
      NIBSC 07/364). Immunoreactivity patterns, isoelectric points and oligosaccharide
      contents of hCGs were evaluated using reducing and non-reducing Western blotting,
      capillary isoelectric-focusing immunoassay and lectin-ELISA, respectively.
      Functional studies were performed in order to evaluate intracellular and total
      cAMP, progesterone production and beta-arrestin 2 recruitment by ELISA and BRET,
      in both human primary granulosa lutein cells (hGLC) and luteinizing hormone
      (LH)/hCG receptor (LHCGR)-transfected HEK293 cells, stimulated by increasing
      hormone concentrations. Statistical analysis was performed using two-way ANOVA
      and Bonferroni post-test or Mann-Whitney's U-test as appropriate. MAIN RESULTS
      AND THE ROLE OF CHANCE: Heterogeneous profiles were found among preparations,
      revealing specific molecular weight patterns (20-75 KDa range), isoelectric
      points (4.0-9.0 pI range) and lectin binding (P < 0.05; n = 7-10). These drug
      specific compositions were linked to different potencies on cAMP production (EC50
      1.0-400.0 ng/ml range) and beta-arrestin 2 recruitment (EC50 0.03-2.0 MUg/ml) in
      hGLC and transfected HEK293 cells (P < 0.05; n = 3-5). In hGLC, these differences
      were reflected by preparation-specific 8-h progesterone production although
      similar plateau levels of progesterone were acheived by 24-h treatment (P >=
      0.05; n = 3). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The
      biological activity of commercial hCG/hMG preparations is provided in
      International Units (IU) by in-vivo bioassay and calibration against an
      International Standard, although it is an unsuitable unit of measure for in-vitro
      studies. The re-calibration against recombinant hCG,quantified in grams, is based
      on the assumption that all of the isoforms and glycosylation variants have
      similar immunoreactivity. WIDER IMPLICATIONS OF THE FINDINGS: hCG/hMG preparation
      specific cell responses in vitro may be proposed to ART patients affected by
      peculiar ovarian response, such as that caused by polycystic ovary syndrome.
      Otherwise, all the preparations available for ART may provide a similar clinical
      outcome in healthy women. STUDY FUNDING AND COMPETING INTEREST(S): This study was
      supported by a grant of the Italian Ministry of Education, University and
      Research (PRIN 2015XCR88M). The authors have no conflict of interest.

PMID- 29044422
TI  - The response of the innate immune and cardiovascular systems to LPS in pregnant
      and nonpregnant mice.
AB  - Sepsis is the leading cause of direct maternal mortality, but there are no data
      directly comparing the response to sepsis in pregnant and nonpregnant (NP)
      individuals. This study uses a mouse model of sepsis to test the hypothesis that
      the cardiovascular response to sepsis is more marked during pregnancy. Female CD1
      mice had radiotelemetry probes implanted and were time mated. NP and day 16
      pregnant CD-1 mice received intraperitoneal lipopolysaccharide (LPS; 10 MUg,
      serotype 0111: B4). In a separate study, tissue and serum (for RNA, protein and
      flow cytometry studies), aorta and uterine vessels (for wire myography) were
      collected after LPS or vehicle control administration. Administration of LPS
      resulted in a greater fall in blood pressure in pregnant mice compared to NP
      mice. This occurred with similar changes in the circulating levels of cytokines,
      vasoactive factors, and circulating leukocytes, but with a greater monocyte and
      lesser neutrophil margination in the lungs of pregnant mice. Baseline markers of
      cardiac dysfunction and apoptosis as well as cytokine expression were higher in
      pregnant mice, but the response to LPS was similar in both groups as was the ex
      vivo assessment of vascular function. In pregnant mice, nonfatal sepsis is
      associated with a more marked hypotensive response but not a greater immune
      response. We conclude that endotoxemia induces a more marked hypotensive response
      in pregnant compared to NP mice. These changes were not associated with a more
      marked systemic inflammatory response in pregnant mice, although monocyte lung
      margination was greater. The more marked hypotensive response to LPS may explain
      the greater vulnerability to some infections exhibited by pregnant women.

PMID- 29044423
TI  - Cultured bovine embryo biopsy conserves methylation marks from original embryo.
AB  - A major limitation of embryo epigenotyping by chromatin immunoprecipitation
      analysis is the reduced amount of sample available from an embryo biopsy. We
      developed an in vitro system to expand trophectoderm cells from an embryo biopsy
      to overcome this limitation. This work analyzes whether expanded trophectoderm
      (EX) is representative of the trophectoderm (TE) methylation or adaptation to
      culture has altered its epigenome. We took a small biopsy from the trophectoderm
      (30-40 cells) of in vitro produced bovine-hatched blastocysts and cultured it on
      fibronectin-treated plates until we obtained ~4 * 104 cells. The rest of the
      embryo was allowed to recover its spherical shape and, subsequently, TE and inner
      cell mass were separated. We examined whether there were DNA methylation
      differences between TE and EX of three bovine embryos using whole-genome
      bisulfite sequencing. As a consequence of adaptation to culture, global
      methylation, including transposable elements, was higher in EX, with 5.3% of
      quantified regions showing significant methylation differences between TE and EX.
      Analysis of individual embryos indicated that TE methylation is more similar to
      its EX counterpart than to TE from other embryos. Interestingly, these similarly
      methylated regions are enriched in CpG islands, promoters and transcription units
      near genes involved in biological processes important for embryo development. Our
      results indicate that EX is representative of the embryo in terms of DNA
      methylation, thus providing an informative proxy for embryo epigenotyping.

PMID- 29044424
TI  - New hope for symptom management during natural and iatrogenic menopause
      transitions.
AB  - Bone loss is associated with aging and is exacerbated by female transition to
      menopause. Estrogen has long been associated with bone loss, and replacement
      therapy is effective at restoring bone health. In the last 10 years, pituitary
      and gonadal peptide hormones have been implicated in bone biology, and here we
      update the story on FSH and its potential role as a direct regulator of bone and
      adipose. If translated to humans, new approaches to ameliorate age related bone
      demise could be developed. Moreover, young women with hormone responsive cancers
      who are unable to maintain bone may have new routes to avoid debilitating bone
      loss.

PMID- 29044425
TI  - SMAD7 regulates proinflammatory and prolabor mediators in amnion and myometrium.
AB  - Preterm birth continues to be a significant public health problem. Infection
      (bacterial and or viral) and inflammation, by stimulating proinflammatory
      cytokines, adhesion molecules, and matrix metalloproteinase 9 (MMP9), play a
      central role in the rupture of membranes and myometrial contractions. SMAD7 has
      been implicated in regulating the inflammatory response; however, no studies have
      been performed with regard to human labor. In this study, we determined the
      effect of spontaneous human labor and prolabor mediators on SMAD7 expression in
      myometrium and fetal membranes. Functional studies were employed to investigate
      the effect of siRNA knockdown of SMAD7 (siSMAD7) in regulating infection and
      inflammation-induced prolabor mediators. SMAD7 mRNA and protein expression were
      significantly higher with spontaneous term labor, compared to no labor, in
      myometrium and fetal membranes. SMAD7 expression was also significantly higher in
      amnion from women with preterm chorioamnionitis. The proinflammatory cytokines
      IL1B and TNF, the bacterial product fsl-1, and the viral dsRNA analog poly(I:C)
      significantly increased SMAD7 in myometrial cells and amnion cells. In myometrial
      cells, siSMAD7 cells significantly decreased cytokine (IL6) and chemokine (CXCL1,
      CXCL8, CCL2 are also known as GRO-alpha, interleukin (IL)-8 and monocyte
      chemotactic protein-1 (MCP-1)) production induced by IL1B, TNF, and fsl-1. There
      was also a decrease in the expression of adhesion molecules intercellular
      adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) in
      siSMAD7 cells, and MMP9 expression. In amnion, siSMAD7 cells treated with IL1B
      also decreased cytokine and chemokine production, ICAM1 and MMP9 expression. In
      conclusion, we report a proinflammatory role for SMAD7 in human gestational
      tissues, with SMAD7 silencing attenuating the inflammatory response.

PMID- 29044426
TI  - P2X7 receptor blockade prevents preterm birth and perinatal brain injury in a
      mouse model of intrauterine inflammation.
AB  - The P2X7 is an adenosine triphosphate (ATP)-gated ion channel involved in several
      facets of immune activation and neuronal function through its importance in
      interleukin (IL)-1beta secretion. We hypothesized that blockade of P2X7 would
      prevent perinatal brain injury associated with exposure to intrauterine (IU)
      inflammation. Dams received 45 mg/kg of Brilliant Blue G (BBG), a specific P2X7
      receptor (P2X7R) antagonist, on gestation day 17 (E17) prior to administration of
      lipopolysaccharide (LPS) or phosphate-buffered saline (PBS). Furthermore, we
      utilized embryo transfer experiments to delineate whether the P2X7 was the key
      mediator of IU inflammation-associated brain injury on maternal or fetal sides.
      In these experiments, P2X7-/- dams were embryo-transferred wild type embryos and
      wild type dams were embryo-transferred P2X7-/- embryos. In the mouse model of
      intrauterine inflammation, pharmacologic blockade of P2X7R reduced preterm birth
      rate, improved offspring performance on neuromotor tests as well as the dendritic
      arborization and density of cortical neurons. Embryo transfer experiments
      demonstrated the importance of maternal P2X7R in IU inflammation-mediated effects
      on offspring. Both genetic and pharmacologic blockade of IL-1beta signaling, by
      targeting maternal P2X7R, ameliorated perinatal brain injury following exposure
      to IU inflammation. Specific targeting of maternal P2X7R may provide a clinically
      useful tool to prevent both preterm birth and prematurity-associated perinatal
      brain injury, and further studies are urgently needed.

PMID- 29044427
TI  - Genomic identification, expression profiling, and functional characterization of
      CatSper channels in the bovine.
AB  - Cation channels of sperm (CatSper) are sperm-specific calcium channels with
      identified roles in the regulation of sperm function in humans, mice, and horses.
      We sought to employ a comparative genomics approach to identify conserved CATSPER
      genes in the bovine genome, and profile their expression in reproductive tissue.
      We hypothesized that CATSPER proteins expressed in bull testicular tissue
      mediates sperm hyperactivation and their rheotactic response in the reproductive
      tract of the cow. Bioinformatic analysis identified all four known CATSPER genes
      (CATSPER 1-4) in the bovine genome, and profiling by quantitative real-time
      polymerase chain reaction identified site-specific variation in messenger
      ribonucleic acid (mRNA) expression for all four genes along the reproductive
      tract of the bull. Using a novel antibody against CATSPER 1, protein expression
      was confirmed and localized to the principal piece of bull sperm, in agreement
      with what has been reported in other species. Subsequent treatment of bull sperm
      with either the calcium chelator ethylene glycol tetraacetic acid; mibefradil, a
      specific blocker of CatSper channels in human sperm; or CATSPER1 antibody all
      significantly inhibited caffeine-induced hyperactivation and the rheotactic
      response, supporting the concept that the calcium influx occurs via CatSper
      channels. Taken together, the work here provides novel insights into expression
      and function of CatSper channels in bull testicular tissue and in the function of
      ejaculated sperm.

PMID- 29044428
TI  - Expression of STRA8 is conserved in therian mammals but expression of CYP26B1
      differs between marsupials and mice.
AB  - The first sign of mammalian germ cell sexual differentiation is the initiation of
      meiosis in females and of mitotic arrest in males. In the mouse, retinoic acid
      induces ovarian Stra8 expression and entry of germ cells into meiosis. In
      developing mouse testes, cytochrome P450 family 26, subfamily b, polypeptide 1
      (CYP26B1) produced by the Sertoli cells degrades retinoic acid, preventing
      Stimulated by Retinoic Acid Gene 8 (Stra8), expression and inhibiting meiosis.
      However, in developing humans, there is no evidence that CYP26B1 acts a meiosis
      inhibiting factor. We therefore examined aspects of the retinoic
      acid/STRA8/CYP26B1 pathway during gonadal development in the tammar wallaby, a
      marsupial, to understand whether retinoic acid stimulation of STRA8 and CYP26B1
      degradation of retinoic acid was conserved between widely divergent mammals. In
      tammar ovaries, as in human ovaries and unlike the pattern in mice, CYP26B1
      expression was not downregulated before the onset of meiosis. Exposure of pre
      meiotic tammar ovaries to exogenous retinoic acid in vitro upregulated STRA8
      expression compared to controls. We conclude that retinoic acid and STRA8 are
      conserved factors that control the initiation of meiosis amongst mammals but the
      role of CYP26B1 as a meiosis-inhibiting factor may be specific to rodents. The
      identity of the marsupial meiosis-inhibiting factor remains unknown.

PMID- 29044429
TI  - Dynamic expression of long noncoding RNAs reveals their potential roles in
      spermatogenesis and fertility.
AB  - Mammalian reproduction requires that males and females produce functional haploid
      germ cells through complex cellular differentiation processes known as
      spermatogenesis and oogenesis, respectively. While numerous studies have
      functionally characterized protein-coding genes and small noncoding RNAs
      (microRNAs and piRNAs) that are essential for gametogenesis, the roles of
      regulatory long noncoding RNAs (lncRNAs) are yet to be fully characterized.
      Previously, we and others have demonstrated that intergenic regions of the
      mammalian genome encode thousands of long noncoding RNAs, and many studies have
      now demonstrated their critical roles in key biological processes. Thus, we
      postulated that some lncRNAs may also impact mammalian spermatogenesis and
      fertility. In this study, we identified a dynamic expression pattern of lncRNAs
      during murine spermatogenesis. Importantly, we identified a subset of lncRNAs and
      very few mRNAs that appear to escape meiotic sex chromosome inactivation, an
      epigenetic process that leads to the silencing of the X- and Y-chromosomes at the
      pachytene stage of meiosis. Further, some of these lncRNAs and mRNAs show a
      strong testis expression pattern suggesting that they may play key roles in
      spermatogenesis. Lastly, we generated a mouse knockout of one X-linked lncRNA,
      Tslrn1 (testis-specific long noncoding RNA 1), and found that males carrying a
      Tslrn1 deletion displayed normal fertility but a significant reduction in
      spermatozoa. Our findings demonstrate that dysregulation of specific mammalian
      lncRNAs is a novel mechanism of low sperm count or infertility, thus potentially
      providing new biomarkers and therapeutic strategies.

PMID- 29044430
TI  - Molecular regulation of sex change induced by methyltestosterone -feeding and
      methyltestosterone -feeding withdrawal in the protogynous orange-spotted grouper.
AB  - The sex identity of fish can be easily manipulated by exogenous hormones.
      Treatment with 17-methyltestosterone (MT) has been widely used to induce a male
      fate, but the molecular and cellular processes underlying sex changes induced by
      MT treatments and the withdrawal of MT are not well studied. In this study, we
      systematically investigated gonadal histology, gene expression profiles, sex
      steroid hormone levels, and cellular changes during sex changes induced by MT
      feeding and MT-feeding withdrawal in the protogynous orange-spotted grouper,
      Epinephelus coioides. Based on gonadal histology, we demonstrated that MT-feeding
      induced sex reversal can be divided into early and late phases: in the early
      phase, male and female germ cells coexist, and MT-feeding withdrawal leads to a
      female fate; in the late phase, only male germ cells are observed, and MT-feeding
      withdrawal does not reverse the process, leading to a male fate. In both the
      early and late phases, cytochrome P450 family19 subfamily A member 1 (cyp19a1a)
      gene expression increased in response to MT-feeding withdrawal. Finally, by
      tracing doublesex- and Mab-3-related transcription factor 1 (dmrt1)-expressing
      cells, we found that gonia-like cells in the germinal epithelium might be the
      major germ cell sources for developing testes during sex reversal. Collectively,
      our findings provide insights into the molecular and cellular mechanisms
      underlying sex changes induced by exogenous hormones.

PMID- 29044432
TI  - Gordon Niswender, Ph.D., 1940-2017.

PMID- 29044431
TI  - Computational imaging of sperm locomotion.
AB  - Not only essential for scientific research, but also in the analysis of male
      fertility and for animal husbandry, sperm tracking and characterization
      techniques have been greatly benefiting from computational imaging. Digital image
      sensors, in combination with optical microscopy tools and powerful computers,
      have enabled the use of advanced detection and tracking algorithms that
      automatically map sperm trajectories and calculate various motility parameters
      across large data sets. Computational techniques are driving the field even
      further, facilitating the development of unconventional sperm imaging and
      tracking methods that do not rely on standard optical microscopes and objective
      lenses, which limit the field of view and volume of the semen sample that can be
      imaged. As an example, a holographic on-chip sperm imaging platform, only
      composed of a light-emitting diode and an opto-electronic image sensor, has
      emerged as a high-throughput, low-cost and portable alternative to lens-based
      traditional sperm imaging and tracking methods. In this approach, the sample is
      placed very close to the image sensor chip, which captures lensfree holograms
      generated by the interference of the background illumination with the light
      scattered from sperm cells. These holographic patterns are then digitally
      processed to extract both the amplitude and phase information of the spermatozoa,
      effectively replacing the microscope objective lens with computation. This
      platform has further enabled high-throughput 3D imaging of spermatozoa with
      submicron 3D positioning accuracy in large sample volumes, revealing various rare
      locomotion patterns. We believe that computational chip-scale sperm imaging and
      3D tracking techniques will find numerous opportunities in both sperm related
      research and commercial applications.

PMID- 29044433
TI  - Pregnancy-induced changes in metabolome and proteome in ovine uterine flushings.
AB  - Mass spectrometry (MS) approaches were used herein to identify metabolites and
      proteins in uterine flushings (UF) that may contribute to nourishing the
      conceptus. Ovine uteri collected on Day 12 of the estrous cycle (n = 5 ewes
      exposed to vasectomized ram) or Days 12 (n = 4), 14 (n = 5), or 16 (n = 5) of
      pregnancy (bred with fertile ram) were flushed using buffered saline. Metabolites
      were extracted using 80% methanol and profiled using ultraperformance liquid
      chromatography (LC) tandem mass spectrometry. The proteome was examined by
      digestion with trypsin, followed by the analysis of peptides with LC-MS/MS.
      Metabolite profiling detected 8510 molecular features of which 9 were detected
      only in UF from Day 14-16 pregnant ewes that function in fatty acid transport
      (carnitines), hormone synthesis (androstenedione like), and availability of
      nutrients (valine). Proteome analysis detected 783 proteins present by Days 14-16
      of pregnancy in UF, 7 of which are as follows: annexin (ANX) A1, A2, and A5;
      calcium-binding protein (S100A11); profilin 1; trophoblast kunitz domain protein
      1 (TKDP); and interferon tau (IFNT). These proteins function in endocytosis,
      exocytosis, calcium signaling, and inhibition of prostaglandins (annexins and
      S100A11); protecting against maternal proteases (TKDP); remodeling cytoskeleton
      (profilin 1); and altering uterine release of prostaglandin F2 alpha as well as
      inducing IFNT-stimulated genes in the endometrium and the corpus luteum (IFNT).
      Identifying metabolites and proteins produced by the uterus and conceptus
      advances our understanding of embryo/maternal signaling and provides insights
      into possible the causes of reproductive failure.

PMID- 29044434
TI  - GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells.
AB  - Feeding-related metabolic factors exert regulatory influences on the hypothalamic
      pituitary-gonadal axis. Glucagon-like peptide-1 (GLP-1) is an anorexigenic
      hormone synthesized from the ileum in response to food intake. The purpose of
      this study was to examine the direct effect of GLP-1 on hypothalamic kisspeptin
      and gonadotropin-releasing hormone (GnRH) expression using the rat clonal
      hypothalamic cell line rHypoE-8. GLP-1 significantly increased Kiss-1 mRNA
      expression in rHypoE-8 cells up to 1.94 +/- 0.22-fold. This effect of GLP-1 on
      Kiss-1 gene expression was also observed in GT1-7 GnRH-producing neurons and in
      primary cultures of fetal rat brain. GLP-1 increased cAMP-mediated signaling, as
      determined by cAMP response element activity assays, but failed to activate
      extracellular signal-regulated kinase pathways. Another anorexigenic factor,
      leptin, similarly increased Kiss-1 mRNA levels up to 1.34 +/- 0.08-fold in rHypoE
      8 cells. However, combined treatment with GLP-1 and leptin failed to potentiate
      their individual effects on Kiss-1 mRNA expression. Gnrh mRNA expression was not
      significantly increased by GLP-1 stimulation in rHypoE-8, but kisspeptin
      significantly stimulated the expression of Gnrh mRNA in these cells. Our current
      observations suggest that the anorexigenic peptide GLP-1 directly regulates Kiss
      1 mRNA expression in these hypothalamic cell lines and in neuronal cells of fetal
      rat brain and affects the expression of Gnrh mRNA.

PMID- 29044435
TI  - Impact of Clinical Parameters in the Intrahost Evolution of HIV-1 Subtype B in
      Pediatric Patients: A Machine Learning Approach.
AB  - Determining the factors modulating the genetic diversity of HIV-1 populations is
      essential to understand viral evolution. This study analyzes the relative
      importance of clinical factors in the intrahost HIV-1 subtype B (HIV-1B)
      evolution and in the fixation of drug resistance mutations (DRM) during
      longitudinal pediatric HIV-1 infection. We recovered 162 partial HIV-1B pol
      sequences (from 3 to 24 per patient) from 24 perinatally infected patients from
      the Madrid Cohort of HIV-1 infected children and adolescents in a time interval
      ranging from 2.2 to 20.3 years. We applied machine learning classification
      methods to analyze the relative importance of 28
      clinical/epidemiological/virological factors in the HIV-1B evolution to predict
      HIV-1B genetic diversity (d), nonsynonymous and synonymous mutations (dN, dS) and
      DRM presence. Most of the 24 HIV-1B infected pediatric patients were Spanish
      (91.7%), diagnosed before 2000 (83.3%), and all were antiretroviral therapy
      experienced. They had from 0.3 to 18.8 years of HIV-1 exposure at sampling time.
      Most sequences presented DRM. The best-predictor variables for HIV-1B
      evolutionary parameters were the age of HIV-1 diagnosis for d, the age at first
      antiretroviral treatment for dN and the year of HIV-1 diagnosis for ds. The year
      of infection (birth year) and year of sampling seemed to be relevant for fixation
      of both DRM at large and, considering drug families, to protease inhibitors (PI).
      This study identifies, for the first time using machine learning, the factors
      affecting more HIV-1B pol evolution and those affecting DRM fixation in HIV-1B
      infected pediatric patients.

PMID- 29044436
TI  - Preterm Infant-Associated Clostridium tertium, Clostridium cadaveris, and
      Clostridium paraputrificum Strains: Genomic and Evolutionary Insights.
AB  - Clostridium species (particularly Clostridium difficile, Clostridium botulinum,
      Clostridium tetani and Clostridium perfringens) are associated with a range of
      human and animal diseases. Several other species including Clostridium tertium,
      Clostridium cadaveris, and Clostridium paraputrificum have also been linked with
      sporadic human infections, however there is very limited, or in some cases, no
      genomic information publicly available. Thus, we isolated one C. tertium strain,
      one C. cadaveris strain and three C. paraputrificum strains from preterm infants
      residing within neonatal intensive care units and performed Whole Genome
      Sequencing (WGS) using Illumina HiSeq. In this report, we announce the open
      availability of the draft genomes: C. tertium LH009, C. cadaveris LH052, C.
      paraputrificum LH025, C. paraputrificum LH058, and C. paraputrificum LH141. These
      genomes were checked for contamination in silico to ensure purity, and we
      confirmed species identity and phylogeny using both 16S rRNA gene sequences (from
      PCR and in silico) and WGS-based approaches. Average Nucleotide Identity (ANI)
      was used to differentiate genomes from their closest relatives to further confirm
      speciation boundaries. We also analysed the genomes for virulence-related factors
      and antimicrobial resistance genes, and detected presence of tetracycline and
      methicillin resistance, and potentially harmful enzymes, including multiple
      phospholipases and toxins. The availability of genomic data in open databases, in
      tandem with our initial insights into the genomic content and virulence traits of
      these pathogenic Clostridium species, should enable the scientific community to
      further investigate the disease-causing mechanisms of these bacteria with a view
      to enhancing clinical diagnosis and treatment.

PMID- 29044437
TI  - A novel dihydrocoumarin under experimental and theoretical characterization.
AB  - Coumarins are natural and synthetic active ingredients widely applied in diverse
      types of medicinal treatments, such as cancer, inflammation, infection, and
      enzyme inhibition (monoamine oxidase B). Dihydrocoumarin compounds are of great
      interest in organic chemistry due to their structural versatilities and, as part
      of our investigations concerning the structural characterization of small
      molecules, this work focuses on crystal structure and spectroscopic
      characterization of the synthesized and crystallized compound 4-(4-methoxyphenyl)
      3,4-dihydro-chromen-2-one (C16H14O3). Additionally, a theoretical calculation was
      performed using density functional theory to analyze the sites where nucleophilic
      or electrophilic attack took place and to examine the molecular electrostatic
      potential surface. Throughout all of these calculations, both density functional
      theory and Car-Parrinello molecular dynamics were performed by fully optimized
      geometry. The spectroscopic analysis indicated the presence of aromatic carbons
      and hydrogen atoms, and also the carbonyl and methoxy groups that were confirmed
      by the crystallographic structure. The C16H14O3 compound has a non-classical
      intermolecular interaction of type C-H???O that drives the molecular arrangement
      and the crystal packing. Moreover, the main absorbent groups were characterized
      throughout calculated harmonic vibrational frequencies. Also, natural bond
      orbital analysis successfully locates the molecular orbital with pi-bonding
      symmetry and the molecular orbital with pi* antibonding symmetry. Finally, the
      gap between highest occupied and lowest unoccupied molecular orbitals implies in
      a high kinetic stability and low chemical reactivity of title molecule.

PMID- 29044438
TI  - High total volatile organic compounds pollution in a hospital dental department.
AB  - Bioaerosols produced by dental procedures may affect indoor air quality and cause
      infections in dental healthcare workers. To provide air quality data that can be
      used to protect dental healthcare workers, this study evaluated the air quality
      and its influencing factors in the dental department of the Chang Gung Memorial
      Hospital in Taiwan. The study was a cross-sectional study design. Indoor air
      quality (IAQ) evaluations were conducted in six locations: pediatric dentistry,
      craniofacial orthodontic dentistry, periodontal dentistry, and general practice
      dentistry, instrument washing room, and patient waiting area. The measured air
      quality parameters included temperature, relative humidity, and concentrations of
      CO2, total volatile organic compounds (TVOCs), suspended particulate matter (PM),
      and bacteria. TVOCs concentrations at all six sampling stations were found to
      exceed the indoor air quality standards prescribed by the Taiwan Environmental
      Protection Agency. The highest concentrations of atmospheric PM10, PM2.5, and PM1
      were found in the periodontal dentistry department, while the lowest
      concentrations occurred in the patient waiting area. The detection rate for Gram
      positive bacteria was highest in the pediatric department (25%) and lowest in the
      instrument washing room (9%). Micrococcus luteus and Bacillus cereus were the
      primary pathogens detected. The dental departments of the hospital had a serious
      TVOCs pollution. The air quality of dental departments deserves long-term
      surveillance and attention.

PMID- 29044440
TI  - Meeting the Canadian 24-Hour Movement Guidelines for Children and Youth.
AB  - BACKGROUND: The Canadian 24-Hour Movement Guidelines for Children and Youth: An
      Integration of Physical Activity, Sedentary Behaviour, and Sleep, provide
      specific recommendations on the amount of time over a typical 24-hour day that
      children and youth aged 5 to 17 should spend in moderate-to-vigorous physical
      activity (at least 60 minutes), recreational screen time (no more than 2 hours),
      and sleep (9 to 11 hours for 5- to 13-year-olds; 8 to 10 hours for 14- to 17-year
      olds). DATA AND METHODS: Based on combined results of cycles 2 (2009-to-2011) and
      3 (2012-to-2013) of the Canadian Health Measures Survey, this analysis examines
      average daily moderate-to-vigorous physical activity, screen time and sleep
      duration of 5- to 11-year-olds and 12- to 17-year-olds, and the percentages
      meeting the 24-Hour Guidelines' recommendations. Findings are presented overall
      and by age group and sex. Differences in average daily times between groups were
      tested for statistical significance, as weredifferences between groups in the
      percentages meeting each recommendation and combination of recommendations.
      RESULTS: Overall, 17.5% of children and youth met the 24-Hour Guidelines'
      specific time recommendations. Higher percentages of children than youth (29.6%
      versus 5.5%) and boys than girls (22.9% versus 11.8%) met the recommendations.
      About a third (36.3%) met two of the three recommendations. INTERPRETATION:
      Recommendations for moderate-to-vigorous physical activity, sedentary behaviour,
      and sleep have higher levels of adherence among children than youth.

PMID- 29044439
TI  - Liver Masses: What Physicians Need to Know About Ordering and Interpreting Liver
      Imaging.
AB  - PURPOSE OF REVIEW: This paper reviews diagnostic imaging techniques used to
      characterize liver masses and the imaging characteristics of the most common
      liver masses. RECENT FINDINGS: The role of recently adopted ultrasound and
      magnetic resonance imaging contrast agents will be emphasized. Contrast-enhanced
      ultrasound is an inexpensive exam which can confirm benignity of certain liver
      masses without ionizing radiation. Magnetic resonance imaging using hepatocyte
      specific gadolinium-based contrast agents can help confirm or narrow the
      differential diagnosis of liver masses.

PMID- 29044441
TI  - Physical activity of Canadian children and youth, 2007 to 2015.
AB  - BACKGROUND: This study describes and compares the percentages of Canadian
      children and youth who adhere to different operational definitions of the
      moderate-to-vigorous physical activity (MVPA) recommendation of 60 minutes per
      day. DATA AND METHODS: Data for 6- to 17-year-olds (n = 5,608) were collected
      from 2007 through 2015 as part of the Canadian Health Measures Survey. MVPA was
      measured using the Actical accelerometer. The MVPA recommendation was
      operationalized as accumulating 60 minutes of MVPA every day, on most days, and
      on average. RESULTS: Data from the most recent cycle of the Canadian Health
      Measures Survey indicate that 7% of children and youth accumulated at least 60
      minutes of MVPA on at least 6 out of 7 days, and 33% achieved a weekly average of
      at least 60 minutes per day. Boys accumulated more MVPA than did girls, and 6- to
      11-year-olds accumulated more MVPA than did 12- to 17-year-olds. Regardless of
      how adherence to the recommendation is operationalized, MVPA levels among
      Canadian children and youth did not change over the 9-year period from 2007 to
      2015. INTERPRETATION: The majority of Canadian children do not meet the physical
      activity recommendation, regardless of the operational definition used. However,
      the discrepancies between results based on different interpretations of the 60
      minutes-per-day recommendation highlight the importance of explicitly reporting
      how recommendations are operationalized to avoid misinterpreting trends and
      comparisons.

PMID- 29044442
TI  - Concurrent mental and substance use disorders in Canada.
AB  - Based on results of the 2012 Canadian Community Health Survey-Mental Health, 1.2%
      of Canadians aged 15 to 64 (an estimated 282,000) experienced mental and
      substance use disorders concurrently in the previous year (at least one
      mood/anxiety disorder and one substance use disorder). Demographic,
      socioeconomic, health status and service use characteristics of the concurrent
      disorder group were compared with those of people who had only a mood/ anxiety
      disorder or only a substance use disorder. Those with concurrent disorders had
      consistently poorer psychological health and higher use of health services and
      were more likely to report partially met/unmet needs than the substance use
      disorder group, even when demographic and socioeconomic factors and number of
      chronic health conditions were taken into account. Apparent similarities in
      health status, service use and partially met/unmet needs between the concurrent
      disorders and mood/anxiety disorder groups did not persist in multivariate
      analysis. The findings suggest that the complexity of concurrent disorders
      contributes to poorer psychological health outcomes and higher health service
      use, compared with having only a mood/anxiety disorder or a substance use
      disorder.

PMID- 29044443
TI  - Needs for mobility devices, home modifications and personal assistance among
      Canadians with disabilities.
AB  - BACKGROUND: People with disabilities often require assistive devices,
      modifications to their home environment, and physical assistance to facilitate
      mobility. This study examines self-reported met and unmet needs of people with
      disabilities who use wheeled mobility devices, compared with non-users. DATA AND
      METHODS: The 2012 Canadian Survey on Disability followed up with 45,442
      individuals who reported a disability on the 2011 National Household Survey, and
      obtained a 75% response rate. Descriptive statistics with variance estimates and
      95% confidence intervals were used to compare wheeled mobility device users and
      non-users. RESULTS: Nearly 10% of wheeled mobility device users identified an
      unmet need for an additional mobility device. Compared with non-users, they were
      twice as likely to modify their home with a ramp and three times as likely to
      install a lift. The prevalence of unmet need for each type of residence
      adaptation among wheeled mobility device users was at least double that of non
      users. Wheeled mobility device users received assistance with an average of 4.4
      activities, compared with 2.0 for non-users, and reported an average of 1.9
      activities for which assistance was needed but not received. About one in three
      relied on paid assistance; for 14% of those who paid for assistance, out-of
      pocket expenses amounted to $10,000 or more annually, compared with 2% among non
      users. INTERPRETATION: Wheeled mobility device users reported a higher prevalence
      of met and unmet needs for residence modifications than did non-users. They
      required help with more activities of life on a more frequent basis, with greater
      dependence on paid individuals, resulting in higher out-of-pocket expenses. Power
      and manual wheelchair users reported greater needs than did mobility scooter
      users.

PMID- 29044444
TI  - Characteristics and factors associated with depression in the elderly in Spain
      from a gender perspective.
AB  - INTRODUCTION: Depression is a main cause of disability and it is a priority
      public health problem among the elderly because of its significant consequences
      regarding morbidity and mortality, especially in women. METHODS: We selected
      records of people aged 65 and over out of the 2014 European Health Survey in
      Spain (n=6,520). We then performed a descriptive analysis stratified by gender of
      relevant variables such as demographic, socioeconomic, health status, health care
      and health determinants. We studied its connection with the presence of
      depressive disorders diagnosed by the PHQ-8 questionnaire. In a second phase we
      adjusted logistic regression models in order to assess depressive disorders based
      on the significant variables. RESULTS: 12.6% of depressive disorders are detected
      (16.8% women; 7.1% men). Many of the variables are related to depressive
      disorders in bivariate analysis; however, only a regular or bad/very bad
      perceived state of health (ORm=6.7; ORw=3.8); bedrest; the difficulty or
      inability to walk; and severe (ORm=3.5, ORw=2) and extreme pain (ORm=5; ORw=3.9)
      remain after multivariate adjustment in both sexes. Differentially depression in
      women is connected with not being able to read or write, the presence of chronic
      disease, and lack of interest from others; and in men a moderate degree of pain.
      CONCLUSIONS: The greater frequency and vulnerability of depression in elderly
      women may be connected to their educational level, their suffering from chronic
      diseases and social support. Longitudinal studies need to be undertaken to
      confirm the role and influence of these factors.

PMID- 29044445
TI  - Development of a screening test for cognitive impairment in alcoholic population:
      TEDCA.
AB  - INTRODUCTION: Several studies have found cognitive impairment in patients with a
      history of alcohol use disorder, affecting their psychosocial functioning and the
      achievement of therapeutic goals. In order to identify these effects, several
      cognitive screening tests have been used, though they were not specific for
      alcoholic population, possibly leading to an increase in the risk of error.
      OBJECTIVE: The aim of this study is to assess the main cognitive deficits in
      patients with history of alcohol use disorders, through the development of a
      specific screening test for alcohol-related cognitive impairment. METHODOLOGY:
      The TEDCA (Test of detection of cognitive impairment in alcoholism) was designed
      based on three dimensions: Visuospatial Cognition, Memory / Learning and
      Executive Function. The study was divided in two phases: During phase 1, test
      items with greater capacity for discrimination between patients with different
      levels of cognitive impairment were selected, and during phase 2, the analysis
      for validity and reliability indexes took place. The sample consisted of 248
      participants, 88 controls (phase 2) and 160 patients (phase 1: n=70 and phase 2:
      n=90). RESULTS: TEDCA test obtained a high reliability (Cronbach&#8217;s alpha
      0.754) value and the factor analysis confirmed the presence of the three
      dimensions previously defined. The present screening tool also discriminated
      between patients and control group, together with a good diagnostic validity of
      cognitive impairment. CONCLUSIONS: TEDCA is a new screening test, which
      identifies the possible presence of cognitive impairment in patients with a
      history of alcohol use disorders, which can be used in the fields of psychiatry,
      primary care and research.

PMID- 29044446
TI  - Social Cognition in Schizophrenia, Unaffected Relatives and Ultra- High Risk for
      Psychosis: What Do We Currently Know?
AB  - INTRODUCTION: Schizophrenia patients show impairments in social cognition (SC),
      which is a set of cognitive processes that underlie social interactions. The
      research about SC in schizophrenia has identified four main domains: Theory of
      mind (ToM), social perception, attributional style and emotional processing. The
      present review aims to summarize the most recent and consistent findings about SC
      in patients with schizophrenia, unaffected relatives and ultra-high risk for
      psychosis individuals (UHR), as well as its association with clinical variables
      and functional outcome. METHODS: A systematic PsycINFO and Pubmed/Medline
      databases search was conducted. RESULTS: ToM impairments have been observed in
      schizophrenia patients, unaffected relatives and UHR. Emotional processing
      disturbance has been consistently reported in schizophrenia patients and UHR. ToM
      and emotional processing have been correlated with symptomatology and functional
      outcome. However, inconsistencies have been found across studies that assess ToM
      and emotional processing as predictors of psychosis. Social perception and
      attributional style are affected in schizophrenia, but the research in at- risk
      populations is scarce, and their relationship with symptoms or functional outcome
      is not clear. CONCLUSIONS: All domains of SC are impaired in schizophrenia. Non
      affected relatives and UHR also display deficits of SC. More research must be
      conducted to assess the reliability of SC domains as endophenotypes or predictors
      of conversion to psychosis in at-risk populations.

PMID- 29044447
TI  - Relationship between androgen deficiency and memory impairment in aging and
      Alzheimer&#8217;s disease.
AB  - Aging and Alzheimer&#8217;s disease (AD) are associated with a declination of
      cognition and memory, whose severity increases in AD. Recent investigations point
      to a greater participation of neurofibrillary tangles (NFTs) than that of senile
      plaques, as responsible for cognitive impairment in AD and normal aging. On the
      other hand, aging is related with reduced levels of dehydroepiandrosterone (DHEA)
      and its sulfate (DHEA-S) as well as testosterone (T). Basic and clinical studies
      give evidence that hypoandrogenism is associated with memory impairment.
      Accordingly, some animal studies show that the administration of these hormones
      improves the performance of cognitive tasks. However, effects of DHEA, DHEA-S,
      and T in the clinical setting, are not clear in part because of the balance
      between the benefits and risks of hormone therapy in aging subjects and because
      the cellular mechanism underlying its effects on memory in old age and related
      pathologies are unknown. The objective of this review is to analyze the role of
      DHEA, DHEA-S, and T, on memory in normal aging and in AD, and to determine
      whether these hormones modulate the hyperphosphorylation of tau protein, a
      molecular marker in AD pathology. The method used in the review included articles
      from the PubMed database, using the following search terms: DHEA, DHEA-S, T,
      memory, androgen deprivation therapy, tau protein, aging, and AD. Finally, we
      analyze the use of these steroids as an adjunct in the treatment of memory
      deficits in aging subjects and AD patients.

PMID- 29044448
TI  - Late paraphrenia, a revisited diagnosis: case report and literature review.

PMID- 29044449
TI  - Cotard&#8217;s Syndrome in a patient with Major Depressive Disorder: Case Report.

PMID- 29044450
TI  - Antipsychotic therapy amongst Cytochrome P450 2D6 poor metabolizers in the
      clinical practice: A case report.

PMID- 29044451
TI  - Pediatric intracranial germinoma: use chemotherapy first.

PMID- 29044452
TI  - Effects of alpha lipoic acid on motor function and antioxidant enzyme activity of
      nerve tissue after sciatic nerve crush injury in rats.
AB  - AIM: Background: Alpha lipoic acid (ALA) that is a strong antioxidant drug is
      tried for both protection and treatment of various diseases of central and
      peripheral nervous systems. MATERIAL AND METHODS: Material and Methods:
      Protective effects of ALA on crush type peripheral nerve injury were evaluated.
      28 Sprague-Dawley rats were divided into four groups: In Group 1, sciatic nerve
      was only explored. Sciatic nerve crush injury was performed after serum
      physiologic injection intraperitoneally in Group 2, and after ALA injection in
      Groups 3 and 4. In all subjects, Sciatic Functional Index (SFI) was calculated.
      All subjects were sacrificed 1 hour after injury in first three groups, and 48
      hours after in Group 4. Nerve samples were taken. Superoxide dismutase, catalase
      and glutathione peroxidase activities were measured in nerve tissue. RESULTS:
      Results: Administration of ALA before injury provided significantly better SFI
      values and higher levels of antioxidant enzymes than control group. These effects
      were significantly prominent 48 hours after injury. CONCLUSION: Conclusion: ALA
      that was given before crush type peripheral nerve injury provided to decrease
      damage of the nerve. Specific mechanisms of this effect must be clarified and
      must be shown that it is whether effective when it is given after injury or not.

PMID- 29044453
TI  - Burr hole craniostomy irrigation with and without drainage during surgical
      treatment of chronic subdural hematoma: A retrospective study of 87 cases.
AB  - AIM: To evaluate the surgical treatment of a chronic subdural haematoma (CSDH).
      We compared two surgical treatments of CSDH: burr-hole craniostomy irrigation
      with and without drainage. MATERIAL AND METHODS: We retrospectively studied
      patients with chronic subdural haematomas admitted to our hospital. A total of 87
      patients underwent surgery: 57 were treated via burr-hole irrigation with
      postoperative drainage (Group BD) and 30 were treated via irrigation without
      drainage (Group BI). RESULTS: Two instances of rebleeding developed in Group BD.
      The cerebral cortex did not expand in one case. One instance of rebleeding
      developed in Group BI but the cerebral cortex expanded in all cases. The average
      length of hospitalisation, number of postoperative complications, incidence of
      rebleeding, and extent of expansion of the cerebral cortex did not differ between
      the two groups (all P-values 0.05). At the 6-month follow-up, most patients had
      recovered well. The Glasgow Outcome Scale (GOS) revealed no significant
      differences between the groups. No significant difference was found between the
      two surgical treatments in terms of the length of hospitalisation, rebleeding, or
      expansion of the cerebral cortex (which was complete in all but one patient).
      CONCLUSION: We believe that the key feature of CSDH surgery is thorough
      irrigation during the operation; whether to use postoperative drainage is not of
      great importance. We currently use burr-hole irrigation without postoperative
      drainage.

PMID- 29044454
TI  - The Role of telovelar approach in fourth ventricular surgery: a new perspective.
AB  - OBJECTIVE: Evaluation the efficiency of the telovelar approach for 4th
      ventricular lesions through identifying and preserving neurovascular structures.
      METHODS: Forty cases of fourth ventricular tumours using the telovelar approach
      Results: It provides adequate exposure in all cases. The brainstem and posterior
      inferior cerebellar artery (PICA) were early identified and preserved in all
      cases. Potential tumour attachment was observed at the floor of the fourth
      ventricle in twenty two (55%) cases, 5 of them were brain stem glioma. 16 of the
      remaining 17 cases (94%) had focal attachment at any area of the caudal fourth
      ventricular floor and two cases (11, 7%) was attached at any area of the lateral
      aspect of the rostral fourth ventricular floor which was the only point of
      attachment in one of them. None of these tumours infiltrated the area of the
      cerebral aqueduct. Gross total excision was achieved in 45% of cases and near
      total excision was possible in 25% due to focal tumour attachment at one or more
      of the previously mentioned areas. However, debulking was possible in 30%.
      CONCLUSIONS: The main advantage of the telovelar approach is the early
      identification and preservation of the brain stem and PICA and in addition it
      allow for assessment of potential tumour attachment at the aforementioned
      areas.The perspective of the telovelar approach should be directed towards the
      advantage of early identification and preservation of the brain stem and PICA and
      in addition it allow for assessment of potential tumour attachment at the
      aforementioned areas.

PMID- 29044455
TI  - Use of an App-Controlled Neuromuscular Electrical Stimulation System for Improved
      Self-Management of Knee Conditions and Reduced Costs.
AB  - Patients suffering from quadriceps muscle weakness secondary to osteoarthritis or
      after surgeries, such as total knee arthroplasty, appear to benefit from the use
      of neuromuscular electrical stimulation (NMES), which can improve muscle strength
      and function, range of motion, exercise capacity, and quality of life. Several
      modalities exist that deliver this therapy. However, with the ever-increasing
      demand to improve clinical efficiency and costs, digitalize healthcare, optimize
      data collection, improve care coordination, and increase patient compliance and
      engagement, newer devices incorporating technologies that facilitate these
      demands are emerging. One of these devices, an app-controlled home-based NMES
      therapy system that allows patients to self-manage their condition and
      potentially increase adherence to the treatment, incorporates a smartphone-based
      application which allows a cloud-based portal that feeds real-time patient
      monitoring to physicians, allowing patients to be supported remotely and given
      feedback. This device is a step forward in improving both patient care and
      physician efficiency, as well as decreasing resource utilization, which
      potentially may reduce healthcare costs.

PMID- 29044456
TI  - The Geometry of Patient Safety: Horizontal and Vertical Approaches to the Hazards
      of Hospitalization.

PMID- 29044457
TI  - Secondary Prevention Medication Use After Myocardial Infarction in U.S. Nursing
      Home Residents.
AB  - BACKGROUND/OBJECTIVES: Secondary prevention medications are recommended for older
      adults after acute myocardial infarction (AMI), but little is known about whether
      nursing home (NH) residents receive these medications. The objective was to
      evaluate new use of secondary prevention medications after AMI in NH residents
      who were previously nonusers and to evaluate what factors were associated with
      use. DESIGN: Retrospective cohort using linked national Minimum Data Set
      assessments; Online Survey, Certification and Reporting records; and Medicare
      claims. SETTING: U.S. NHs. PARTICIPANTS: National cohort of 11,192 NH residents
      aged 65 and older who were hospitalized for an AMI between May 2007 and March
      2010, had no beta-blocker or statin use for 4 months or longer before the
      hospitalization, and survived 14 days or more after NH readmission. MEASUREMENTS:
      The outcome was the number of secondary prevention medications initiated within
      30 days of NH readmission. RESULTS: Thirty-seven percent of residents had no
      secondary prevention medications initiated after AMI, 41% had 1 initiated, and
      22% had 2 initiated. After covariate adjustment, fewer secondary prevention
      medications were used in older residents (proportional odds ratio (POR) = 0.48,
      95% confidence interval (CI)  = 0.40-0.57 for >=95 vs 65-74); women (POR = 0.88,
      95% CI = 0.80-0.96);and those with a do-not-resuscitate (DNR) order (POR = 0.90,
      95% CI = 0.83-0.98), functional impairment (dependent or totally dependent vs
      independent to limited assistance, POR = 0.77, 95% CI = 0.69-0.86), and cognitive
      impairment (moderate to severe vs no impairment, POR = 0.79, 95% CI = 0.70-0.89).
      CONCLUSION: More than one-third of older NH residents in the United States do not
      have any secondary prevention medications initiated after AMI, with fewer
      medications initiated in older residents; women; and those with, DNR orders, poor
      physical function, and cognitive impairment. A lack of evidence about the safety
      and effectiveness of secondary preventions medications in the NH population and
      unmeasured person-centered goals of care are plausible explanations for these
      findings.

PMID- 29044458
TI  - Patient-reported quality-of-life outcomes after de-escalated chemoradiation for
      human papillomavirus-positive oropharyngeal carcinoma: Findings from a phase 2
      trial.
AB  - BACKGROUND: The current study represents a subset analysis of quality-of-life
      (QOL) outcomes among patients treated on a phase 2 trial of de-escalated
      chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer.
      METHODS: Eligibility included newly diagnosed, (American Joint Committee on
      Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16
      positivity, age >= 18 years, and a Zubrod performance status of 0 to 1. Treatment
      was induction paclitaxel at a dose of 175 mg/m2 and carboplatin at an area under
      the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation
      of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m2 . The
      University of Washington Quality of Life (UW-QOL) and the Functional Assessment
      of Cancer Therapy-Head and Neck questionnaires were used to assess patient
      reported QOL as a secondary endpoint. RESULTS: A total of 45 patients were
      registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for
      overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores
      were reached at 4 weeks after treatment but returned to baseline at 3 months.
      Nearly all functional indices returned to baseline levels by 6 to 9 months. The
      mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3,
      and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy.
      The percentage of patients rating their overall QOL as "very good" or
      "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and
      84%, respectively. CONCLUSIONS: This de-escalation regimen achieved QOL outcomes
      that were favorable compared with historical controls. These results serve as
      powerful evidence that ongoing de-escalation efforts lead to tangible gains in
      function and QOL. Cancer 2018;124:521-9. (c) 2017 American Cancer Society.

PMID- 29044459
TI  - Azacitidine-induced Sweet syndrome: Two unusual clinical presentations.

PMID- 29044460
TI  - A semi-parametric within-subject mixture approach to the analyses of responses
      and response times.
AB  - In item response theory, modelling the item response times in addition to the
      item responses may improve the detection of possible between- and within-subject
      differences in the process that resulted in the responses. For instance, if
      respondents rely on rapid guessing on some items but not on all, the joint
      distribution of the responses and response times will be a multivariate within
      subject mixture distribution. Suitable parametric methods to detect these within
      subject differences have been proposed. In these approaches, a distribution needs
      to be assumed for the within-class response times. In this paper, it is
      demonstrated that these parametric within-subject approaches may produce false
      positives and biased parameter estimates if the assumption concerning the
      response time distribution is violated. A semi-parametric approach is proposed
      which resorts to categorized response times. This approach is shown to hardly
      produce false positives and parameter bias. In addition, the semi-parametric
      approach results in approximately the same power as the parametric approach.

PMID- 29044462
TI  - Urgency of caesarean section, grading, alarm chain and intrauterine resuscitation
      - a survey of Scandinavian practice.
AB  - BACKGROUND: About 40,000 women have caesarean section in Scandinavia each year.
      Organizational factors for emergency caesarean section (CS), classification,
      anaesthetic practice, alarm chain, intrauterine resuscitation has all been
      investigated in the United Kingdom, but no information from the Scandinavian
      countries exists. METHODS: Using publicly available data from the National Board
      of Health, obstetric anaesthetic departments were identified. The heads of the
      departments provided e-mail contact details of two anaesthesiologists regularly
      practicing obstetric anaesthesia who were then surveyed. RESULTS: One hundred and
      forty-five specialists from 82 departments in Scandinavia replied to our survey.
      Ninety-five percent of Danish specialists reported a three-grade classification
      system for urgency CS. Where classification in Denmark was enumerative
      classification, Norwegians equally reported enumerative and verbal descriptors,
      whereas Swedish specialists mostly reported verbal descriptors. Local guidelines
      describing decision-to-delivery interval for emergency CS was reported by 100% of
      Danish specialists vs. 47% from Norway and 85% from Sweden. Mean benchmark
      decision-to-delivery interval for emergency CS was 12.7 min. General anaesthesia
      for emergency CS was highly favoured in Norway (95%) and Sweden (97%), compared
      to Denmark (49%). Twenty specialists reported existence of local guidelines for
      intrauterine resuscitation. CONCLUSION: Our survey of Scandinavian specialists
      indicate emergency CS practise differs from United Kingdom practices in several
      aspects; general anaesthesia is by the majority of Scandinavian specialists
      reported as the default choice for emergency CS and benchmark for decision-to
      delivery interval is < 20 min. Nomenclature used for classification showed
      considerable variance in Norway and Sweden compared to Denmark. No joint
      Scandinavian guidelines exist.

PMID- 29044461
TI  - The influence of time units on the flexibility of the spatial numerical
      association of response codes effect.
AB  - The Spatial Numerical/Temporal Association of Response Codes (SNARC/STEARC)
      effects are considered evidence of the association between number or time and
      space, respectively. As the SNARC effect was proposed by Dehaene, Bossini, and
      Giraux in 1993, several studies have suggested that different tasks and cultural
      factors can affect the flexibility of the SNARC effect. This study explored the
      influence of time units on the flexibility of the SNARC effect via materials with
      Arabic numbers, which were suffixed with time units and subjected to magnitude
      comparison tasks. Experiment 1 replicated the SNARC effect for numbers and the
      STEARC effect for time units. Experiment 2 explored the flexibility of the SNARC
      effect when numbers were attached to time units, which either conflicted with the
      numerical magnitude or in which the time units were the same or different.
      Experiment 3 explored whether the SNARC effect of numbers was stable when numbers
      were near the transition of two adjacent time units. The results indicate that
      the SNARC effect was flexible when the numbers were suffixed with time units:
      Time units influenced the direction of the SNARC effect in a way which could not
      be accounted for by the mathematical differences between the time units and
      numbers. This suggests that the SNARC effect is not obligatory and can be easily
      adapted or inhibited based on the current context.

PMID- 29044463
TI  - Prehospital Delay in Older Adults with Acute Myocardial Infarction: The
      ComprehenSIVe Evaluation of Risk Factors in Older Patients with Acute Myocardial
      Infarction Study.
AB  - BACKGROUND/OBJECTIVES: Timely administration of antiischemic therapies improves
      outcomes in individuals with acute myocardial infarction (AMI). Prior literature
      on delays in AMI care has largely focused on in-hospital delay ("door to balloon"
      time). Our objective was to identify factors associated with prehospital delay in
      a contemporary national cohort of older adults with AMI. DESIGN: Cross-sectional
      analysis of data from the ComprehenSIVe Evaluation of Risk Factors in Older
      Patients with Acute Myocardial Infarction (SILVER-AMI) study, an observational
      study of older adults hospitalized for AMI. SETTING: U.S. academic and community
      hospitals (N = 94). PARTICIPANTS: Individuals aged 75 and older hospitalized for
      AMI (N = 2,500). MEASUREMENTS: Prehospital delay was defined as symptom duration
      of 6 hours or longer before hospital presentation and was obtained according to
      participant or caregiver report during AMI hospitalization. Potential predictors
      of delay from demographic, clinical presentation, comorbid conditions, function,
      and social support domains were obtained through in-person assessment during the
      index hospitalization and medical record abstraction. RESULTS: Nonwhite race
      (adjusted odds ratio (aOR) = 1.54, P = .002), atypical symptoms (aOR = 1.41, P =
      .001), and heart failure (HF) (aOR = 1.35, P = .006 for HF) were significantly
      associated with delay. CONCLUSION: In contrast with younger AMI populations,
      female sex and diabetes mellitus were not associated with delay in this older
      cohort, but factors from other domains (nonwhite race, atypical symptoms, and HF)
      were significantly associated with delay. These results can be used to customize
      future public health efforts to encourage early presentation for older adults
      with AMI.

PMID- 29044464
TI  - Prognostic value of the cancer oncogene Kelch-like 6 in gastric cancer.
AB  - BACKGROUND: Kelch-like 6 (KLHL6) is a cancer oncogene previously associated with
      specific human cancers, such as chronic lymphocytic leukaemia. Here, the
      mechanisms of KLHL6 function were explored in gastric cancer (GC) cells, in an in
      vivo experimental tumour model, and the prognostic value of KLHL6 analysis in GC
      tissue evaluated in a cohort of patients with GC. METHODS: Associations between
      clinicopathological and survival data and KLHL6 expression in GC tissues were
      analysed. The effects of downregulation of KLHL6 in GC cells was investigated
      using proliferation, invasion, apoptosis and lymphangiogenesis assays, and
      analysis of tumour growth in an in vivo experimental model. RESULTS: KLHL6 was
      upregulated in 43 per cent of GC tissues compared with 5 per cent of paired non
      tumour tissues from 84 patients. KLHL6 protein expression in GC tissues was much
      higher than that in atrophic gastritis, intestinal metaplasia and dysplasia
      tissues from benign gastric disease samples. KLHL6 expression was positively
      related to the intestinal Lauren classification in GC tissues. Downregulated
      expression of KLHL6 in MGC-803 GC cells reduced colony formation, proliferation,
      viability, migration and invasion, enhanced apoptosis and inhibited the cell
      cycle in the G1 phase. Downregulated expression of KLHL6 also suppressed tumour
      growth in mice. Furthermore, downregulated expression of KLHL6 mRNA reduced the
      expression of nuclear-associated antigen Ki-67, vascular endothelial growth
      factor C, hepatocyte growth factor and matrix metalloproteinase 2 in vitro, and
      KLHL6 protein in tumour tissue of mice. CONCLUSION: Abnormal expression of the
      KLHL6 oncogene promoted GC progression in vitro and in vivo, and its expression
      level in tumour tissue was found to be of prognostic value.

PMID- 29044465
TI  - Morbidity of cholecystectomy and gastric bypass in a national database.
AB  - BACKGROUND: There is a strong association between obesity and gallstones.
      However, there is no clear evidence regarding the optimal order of Roux-en-Y
      gastric bypass (RYGB) and cholecystectomy when both procedures are clinically
      indicated. METHODS: Based on cross-matched data from the Swedish Register for
      Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (GallRiks; 79
      386 patients) and the Scandinavian Obesity Surgery Registry (SOReg; 36 098
      patients) from 2007 to 2013, complication rates, reoperation rates and operation
      times related to the timing of RYGB and cholecystectomy were explored. RESULTS:
      There was a higher aggregate complication risk when cholecystectomy was performed
      after RYGB rather than before (odds ratio (OR) 1.35, 95 per cent c.i. 1.09 to
      1.68; P = 0.006). A complication after the first procedure independently
      increased the complication risk of the following procedure (OR 2.02, 1.44 to
      2.85; P < 0.001). Furthermore, there was an increased complication risk when
      cholecystectomy was performed at the same time as RYGB (OR 1.72, 1.14 to 2.60; P
      = 0.010). Simultaneous cholecystectomy added 61.7 (95 per cent c.i. 56.1 to 67.4)
      min (P < 0.001) to the duration of surgery. CONCLUSION: Cholecystectomy should be
      performed before, not during or after, RYGB.

PMID- 29044466
TI  - Massage therapy decreases cancer-related fatigue: Results from a randomized early
      phase trial.
AB  - BACKGROUND: Cancer-related fatigue (CRF) is a prevalent and debilitating symptom
      experienced by cancer survivors, yet treatment options for CRF are limited. In
      this study, we evaluated the efficacy of weekly Swedish massage therapy (SMT)
      versus an active control condition (light touch [LT]) and waitlist control (WLC)
      on persistent CRF in breast cancer survivors. METHODS: This early phase,
      randomized, single-masked, 6-week investigation of SMT, LT, and WLC enrolled 66
      female stage 0-III breast cancer survivors (age range, 32-72 years) who had
      received surgery plus radiation and/or chemotherapy/chemoprevention with CRF
      (Brief Fatigue Inventory > 25). The primary outcome was the Multidimensional
      Fatigue Inventory (MFI), with the National Institutes of Health PROMIS Fatigue
      scale secondary. RESULTS: Mean baseline MFI scores for 57 evaluable subjects were
      62.95 for SMT, 55.00 for LT, and 60.41 for WLC. SMT resulted in a mean (standard
      deviation) 6-week reduction in MFI total scores of -16.50 (6.37) (n = 20) versus 
      8.06 (6.50) for LT (n = 20) and an increase of 5.88 (6.48) points for WLC (n =
      17) (treatment-by-time P < .0001). The mean baseline PROMIS Fatigue scores were
      SMT, 22.25; LT, 22.05; and WLC, 23.24. The mean (standard deviation) reduction in
      PROMIS Fatigue scores was -5.49 (2.53) points for SMT versus -3.24 (2.57) points
      for LT and -0.06 (1.88) points for WLC (treatment-by-time P = .0008). Higher
      credibility, expectancy, and preference for SMT than for LT did not account for
      these results. CONCLUSION: SMT produced clinically significant relief of CRF.
      This finding suggests that 6 weeks of a safe, widely accepted manual intervention
      causes a significant reduction in fatigue, a debilitating sequela for cancer
      survivors. Cancer 2018;124:546-54. (c) 2017 American Cancer Society.

PMID- 29044467
TI  - The influence of text cohesion and picture detail on young readers' knowledge of
      science topics.
AB  - BACKGROUND AND AIM: The effects of text cohesion and added pictures on acquired
      knowledge have been heavily studied each in isolation. Furthermore, studies on
      the effects of specific characteristics of pictures, whether facilitating or
      hindering, are scarce. Schnotz's ITCP Model (2014) allows to formulate hypotheses
      regarding the combined effect of text cohesion and presence and level of detail
      of a picture. This study investigates these hypotheses in the case of children
      reading scientific texts. SAMPLE: One hundred and one-second-, third-, and fourth
      grade pupils with a mean age of 9 years, in the western United States. METHODS:
      Data were collected over three sessions to encompass an understanding of each
      pupil's knowledge based on prior sessions. RESULTS AND CONCLUSIONS: Results
      showed a significant increase in pupils' knowledge between pre-test and immediate
      post-test, but as hypothesized, no significant difference between levels of
      cohesion. No significant difference between types of pictures was detected. After
      1 week, knowledge built with a high cohesive text significantly dropped with low
      detail picture, whereas, with high detail, or no picture, there was no
      significant difference. Results suggested that when participants were given a low
      detail picture with a low cohesive text, the integration process of the material
      was more restricted than with a high cohesive text.

PMID- 29044468
TI  - Matchmaker Exchange.
AB  - In well over half of the individuals with rare disease who undergo clinical or
      research next-generation sequencing, the responsible gene cannot be determined.
      Some reasons for this relatively low yield include unappreciated phenotypic
      heterogeneity; locus heterogeneity; somatic and germline mosaicism; variants of
      uncertain functional significance; technically inaccessible areas of the genome;
      incorrect mode of inheritance investigated; and inadequate communication between
      clinicians and basic scientists with knowledge of particular genes, proteins, or
      biological systems. To facilitate such communication and improve the search for
      patients or model organisms with similar phenotypes and variants in specific
      candidate genes, we have developed the Matchmaker Exchange (MME). MME was created
      to establish a federated network connecting databases of genomic and phenotypic
      data using a common application programming interface (API). To date, seven
      databases can exchange data using the API (GeneMatcher, PhenomeCentral, DECIPHER,
      MyGene2, matchbox, Australian Genomics Health Alliance Patient Archive, and
      Monarch Initiative; the latter included for model organism matching). This
      article guides usage of the MME for rare disease gene discovery. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 29044469
TI  - Co-Differentiation of Human Pluripotent Stem Cells-Derived Cardiomyocytes and
      Endothelial Cells from Cardiac Mesoderm Provides a Three-Dimensional Model of
      Cardiac Microtissue.
AB  - The formation of cardiac mesodermal subtypes is highly regulated in time and
      space during heart development. In vitro models based on human pluripotent stem
      cells (hPS cells) provide opportunities to study mechanisms underlying fate
      choices governing lineage specification from common cardiovascular progenitors in
      human embryos. The generation of cardiac endothelial cells in particular allows
      the creation of complex models of cardiovascular disorders in which either
      cardiomyocytes or endothelial cells are affected. Here, a protocol for co
      differentiation of cardiomyocytes and endothelial cells from cardiac mesoderm
      using hPS cells is described. Precise details for the enrichment of each cell
      population from heterogeneous-differentiated cultures, a description of how to
      maintain and dissociate enriched cardiomyocytes, and the expansion and
      cryopreservation of enriched endothelial cells are all provided. The generation
      and culture of three-dimensional cardiac microtissues from these cell populations
      is described and guidelines for the characterization of microtissues by
      immunofluorescent staining and re-plating for downstream applications are
      provided. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29044470
TI  - Analysis of Gene-Gene Interactions.
AB  - The goal of this unit is to introduce epistasis, or gene-gene interactions, as a
      significant contributor to the genetic architecture of complex traits, including
      disease susceptibility. This unit begins with an historical overview of the
      concept of epistasis and the challenges inherent in the identification of
      potential gene-gene interactions. Then, it reviews statistical and machine
      learning methods for discovering epistasis in the context of genetic studies of
      quantitative and categorical traits. This unit concludes with a discussion of
      meta-analysis, replication, and other topics of active research. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 29044471
TI  - Analysis and Annotation of Whole-Genome or Whole-Exome Sequencing Derived
      Variants for Clinical Diagnosis.
AB  - Over the last 10 years, next-generation sequencing (NGS) has transformed genomic
      research through substantial advances in technology and reduction in the cost of
      sequencing, and also in the systems required for analysis of these large volumes
      of data. This technology is now being used as a standard molecular diagnostic
      test in some clinical settings. The advances in sequencing have come so rapidly
      that the major bottleneck in identification of causal variants is no longer the
      sequencing or analysis (given access to appropriate tools), but rather clinical
      interpretation. Interpretation of genetic findings in a complex and ever changing
      clinical setting is scarcely a new challenge, but the task is increasingly
      complex in clinical genome-wide sequencing given the dramatic increase in dataset
      size and complexity. This increase requires application of appropriate
      interpretation tools, as well as development and application of appropriate
      methodologies and standard procedures. This unit provides an overview of these
      items. Specific challenges related to implementation of genome-wide sequencing in
      a clinical setting are discussed. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29044473
TI  - Induced Pluripotent Stem Cells from Ovarian Tissue.
AB  - Yamanaka and colleagues revolutionized stem cell biology and regenerative
      medicine by observing that somatic cells can be reprogrammed into pluripotent
      stem cells. Evidence indicates that induced pluripotent stem (iPS) cells retain
      epigenetic memories that bias their spontaneous differentiation into the
      originating somatic cell type, therefore epigenetic memory may be exploited to
      improve tissue specific regeneration. We recently showed that iPS cells
      reprogrammed from ovarian granulosa cells using mouse and human tissue
      overwhelmingly differentiate homotypically into ovarian steroidogenic and
      primordial germ cells. Herein we detail a protocol for the culture of human
      ovarian granulosa cells. We review approaches for reprogramming human ovarian
      granulosa cells into iPS cells. Standard methods to induce pluripotency are
      outlined, concentrating on integrative retroviruses. Additionally, alternative
      protocols for lentivirus and Sendai virus are provided. Each approach has
      inherent limitations, such as reprogramming efficiency, insertional mutagenesis,
      and partial reprogramming. Major advances continue to be made in somatic cell
      reprogramming to identify an optimal approach and utilization in cell-based
      therapies. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29044472
TI  - Population Stratification in Genetic Association Studies.
AB  - Population stratification (PS) is a primary consideration in studies of genetic
      determinants of human traits. Failure to control for PS may lead to confounding,
      causing a study to fail for lack of significant results, or resources to be
      wasted following false-positive signals. Here, historical and current approaches
      for addressing PS when performing genetic association studies in human
      populations are reviewed. Methods for detecting the presence of PS, including
      global and local ancestry methods, are described. Also described are approaches
      for accounting for PS when calculating association statistics, such that measures
      of association are not confounded. Many traits are being examined for the first
      time in minority populations, which may inherently feature PS. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 29044474
TI  - Exome Sequencing Identifies a Novel Nonsense Mutation of MYO6 as the Cause of
      Deafness in a Brazilian Family.
AB  - We investigated 313 unrelated subjects who presented with hearing loss to
      identify the novel genetic causes of this condition in Brazil. Causative
      GJB2/GJB6 mutations were found in 12.7% of the patients. Among the familial cases
      (100/313), four were selected for exome sequencing. In one case, two novel
      heterozygous variants were found and were predicted to be pathogenic based on
      bioinformatics tools, that is, p.Ser906* (MYO6) and p.Arg42Cys (GJB3). We
      confirmed that this nonsense MYO6 mutation segregated with deafness in this
      family. Only the proband and her unaffected mother exhibited the GJB3 mutation,
      which is in the same amino acid of a known Erythrokeratodermia variabilis
      mutation. None of the patients exhibited this skin disease, but the proband
      exhibited a more severe hearing loss. Hence, the GJB3 mutation was considered to
      be a variant of uncertain significance. In conclusion, we described a novel
      nonsense MYO6 mutation that was responsible for the hearing loss in a Brazilian
      family. This mutation resides in the neck domain of myosin-VI after the motor
      domain. Thus, our data give further support for genotype-phenotype correlations,
      which state that when the motor domain of the protein is functioning, the hearing
      loss is milder and has a later onset. The three remaining families without
      mutations in the known genes suggest that there are still deafness genes to be
      revealed.

PMID- 29044475
TI  - The site of care matters: An examination of the relationship between high
      Medicaid burden hospitals and the use, cost, and complications of immediate
      breast reconstruction after mastectomy.
AB  - BACKGROUND: Diminished use and worse outcomes after immediate breast
      reconstruction (IBR) have been documented for Medicaid beneficiaries. However, to
      the authors' knowledge, the contribution of patient clustering at hospitals with
      a high percentage of Medicaid patients to these inequalities in IBR delivery is
      unknown. METHODS: A cross-sectional analysis of patients undergoing IBR after
      mastectomy using the 2007 to 2011 Nationwide Inpatient Sample database was
      performed. Hospital Medicaid status was calculated as the percentage of all
      patients with Medicaid as a primary payer. Tertile groupings were generated to
      enable statistical analysis. Hierarchical regression models were used to
      investigate the link between Medicaid status and IBR use, outcomes, and costs. A
      subgroup of patients undergoing IBR for noninvasive cancer or those with
      increased genetic risk were used to study IBR use. RESULTS: A total of 30,086 IBR
      cases in 1199 hospitals were analyzed. Hierarchical regression analysis
      demonstrated an association between high Medicaid burden hospitals and
      significantly decreased odds of IBR among patients with in situ disease and/or an
      elevated risk of cancer (odds ratio, 0.64; 95% confidence interval [95% CI],
      0.507-0.806). Increasing age, obesity, being nonwhite, having more comorbid
      conditions, and having government insurance were found to be associated with
      diminished odds of IBR (P<.001 in all instances). In-hospital surgical and
      medical complication rates were comparable across the 3 strata of hospital
      Medicaid status. Log-adjusted costs of care were found to be positively
      associated with a higher hospital Medicaid burden status (coefficient of 0.038
      [95% CI, 0.011-0.066] for medium Medicaid burden hospitals and coefficient of
      0.053 [95% CI, 0.015-0.093] for high Medicaid burden hospitals). CONCLUSIONS:
      High Medicaid burden hospital status is associated with an attenuation of IBR use
      and increased total inpatient costs. Structures of care such as hospital
      resources partially explain disparities in IBR delivery. Cancer 2018;124:346-55.
      (c) 2017 American Cancer Society.

PMID- 29044476
TI  - Treatment of Hailey-Hailey disease with botulinum toxin.

PMID- 29044477
TI  - Association Between Neighborhood Cohesion and Self-Neglect in Chinese-American
      Older Adults.
AB  - OBJECTIVES: To examine the association between neighborhood cohesion and risk of
      self-neglect in a community-dwelling Chinese-American older population. SETTING:
      Community. PARTICIPANTS: Chinese-American older adults aged 60 and older
      interviewed from 2011 to 2013 (N = 3,159). DESIGN: Data were drawn from the
      Population Study of Chinese Elderly, a cross-sectional community-engaged study in
      the greater Chicago area. MEASUREMENTS: Self-neglect was assessed with systematic
      observations of a participant's personal and home environment. Neighborhood
      cohesion was measured using six questions. RESULTS: After controlling for
      potential confounders, greater neighborhood cohesion was significantly associated
      with lower risk of overall self-neglect (odds ratio (OR) = 0.87, 95% confidence
      interval (CI) = 0.77-0.98) and moderate to severe self-neglect (OR = 0.70, 95% CI
      = 0.58-0.85) but not significantly associated with mild self-neglect (OR = 0.94,
      95% CI = 0.82-1.09). Regarding the phenotypes of self-neglect, greater
      neighborhood cohesion was significantly associated with lower risk of poor
      personal hygiene (OR = 0.80, 95% CI = 0.67-0.96) and need for home repair (OR =
      0.70, 95% CI = 0.60-0.83) but not significantly for hoarding (OR = 1.04, 95% CI =
      0.89-1.21), unsanitary conditions (OR = 0.88, 95% CI = 0.76-1.02), and inadequate
      utilities (OR = 1.00, 95% CI = 0.77-1.31). CONCLUSION: This study highlights the
      association between greater neighborhood cohesion and lower risk of overall self
      neglect in Chinese-American older adults. Enhancing neighborhood cohesion may
      enhance elder self-neglect prevention and intervention.

PMID- 29044478
TI  - Enhanced pyruvate production in Candida glabrata by carrier engineering.
AB  - Pyruvate is an important organic acid that plays a key role in the central
      metabolic pathway. Manipulating transporters is an efficient strategy to enhance
      production of target organic acids and a means to understand the effects of
      altered intracellular pyruvate content on global metabolic networks. Efforts have
      been made to manipulate mitochondrial pyruvate carrier (MPC) to transport
      pyruvate into different subcellular compartments in Candida glabrata to
      demonstrate the effects of the subcellular distribution of pyruvate on central
      carbon metabolism. By increasing the mitochondrial pyruvate content through
      enhancing the rate of pyruvate transport into mitochondria, a high central carbon
      metabolism rate, specific growth rate and specific pyruvate production rate were
      obtained. Comparing the intracellular pyruvate content of engineered and control
      strains showed that higher intracellular pyruvate levels were not conducive to
      improving pyruvate productivity or central carbon metabolism. Plasma membrane
      expression of MPCs significantly increased the expression levels of key rate
      limiting glycolytic enzymes. Moreover, pyruvate production of CGDeltaura3-Sp
      MPC1, CGDeltaura3-Sp-MPC2, and CGDeltaura3-Sp-MPC1-Sp-MPC2 increased 134.4%,
      120.3%, and 30.0%, respectively. In conclusion, lower intracellular pyruvate
      content enhanced central carbon metabolism and provided useful clues for
      improving the production of other organic acids in microorganisms.

PMID- 29044480
TI  - Can Physical Activity Prevent Falls in Older Adults with Poor Physical
      Performance?

PMID- 29044479
TI  - The Strategies to Reduce Injuries and Develop Confidence in Elders Intervention:
      Falls Risk Factor Assessment and Management, Patient Engagement, and Nurse Co
      management.
AB  - In response to the epidemic of falls and serious falls-related injuries in older
      persons, in 2014, the Patient Centered Outcomes Research Institute (PCORI) and
      the National Institute on Aging funded a pragmatic trial, Strategies to Reduce
      Injuries and Develop confidence in Elders (STRIDE) to compare the effects of a
      multifactorial intervention with those of an enhanced usual care intervention.
      The STRIDE multifactorial intervention consists of five major components that
      registered nurses deliver in the role of falls care managers, co-managing fall
      risk in partnership with patients and their primary care providers (PCPs). The
      components include a standardized assessment of eight modifiable risk factors
      (medications; postural hypotension; feet and footwear; vision; vitamin D;
      osteoporosis; home safety; strength, gait, and balance impairment) and the use of
      protocols and algorithms to generate recommended management of risk factors;
      explanation of assessment results to the patient (and caregiver when appropriate)
      using basic motivational interviewing techniques to elicit patient priorities,
      preferences, and readiness to participate in treatments; co-creation of
      individualized falls care plans that patients' PCPs review, modify, and approve;
      implementation of the falls care plan; and ongoing monitoring of response,
      regularly scheduled re-assessments of fall risk, and revisions of the falls care
      plan. Custom-designed falls care management software facilitates risk factor
      assessment, the identification of recommended interventions, clinic note
      generation, and longitudinal care management. The trial testing the effectiveness
      of the STRIDE intervention is in progress, with results expected in late 2019.

PMID- 29044481
TI  - Meta-analysis of the association between peripheral artery disease and growth of
      abdominal aortic aneurysms.
AB  - BACKGROUND: The role of atherosclerosis in the pathogenesis of abdominal aortic
      aneurysm (AAA) is controversial. Atherosclerosis-associated peripheral artery
      disease (PAD) has been reported to be a risk factor for AAA in population
      screening studies; its relationship with AAA growth is controversial. METHODS: A
      systematic search of MEDLINE, Scopus, CINAHL and the Cochrane Central Register of
      Controlled Trials was conducted in April 2016 and repeated in January 2017.
      Databases were screened for studies reporting AAA growth rates in patients with,
      and without PAD. The included studies underwent quality assessment and, where
      possible, were included in the meta-analysis. A subgroup analysis was performed,
      including only studies that adjusted for confounding factors. RESULTS: Seventeen
      studies, including a total of 4873 patients, met the review entry criteria. Data
      from 15 studies were included in the meta-analysis. There was marked
      heterogeneity in study design, methodology and statistical analyses used. In the
      main analysis, PAD was associated with reduced AAA growth (mean difference -
      0.13, 95 per cent c.i. -0.27 to -0.00; P = 0.04). However, statistical
      significance was not maintained in sensitivity analysis. In a subanalysis that
      included only data adjusted for other risk factors, no significant association
      between PAD and AAA growth was found (mean difference -0.11, -0.23 to 0.00; P =
      0.05). CONCLUSION: This systematic review suggests that currently reported
      studies demonstrate no robust and consistent association between PAD and reduced
      AAA growth.

PMID- 29044482
TI  - Hematopoietic stem cell transplantation for Gaucher disease.
AB  - BACKGROUND: Gaucher disease is the most common lysosomal storage disorder caused
      by a deficiency of the enzyme glucocerebrosidase. Current treatment of the
      disease involves a choice from enzyme replacement therapy, substrate reduction
      therapy and hemotopoietic stem cell transplantation (HSCT). HSCT is a high risk
      procedure with possible long-term benefits in the regression of skeletal and
      neurological changes in people with Gaucher disease. This is an update of a
      previously published Cochrane Review. OBJECTIVES: To determine the role of HSCT
      in people with Gaucher disease in relation to: mortality risk associated with the
      procedure; efficacy in modifying the course of the disease; and arrest or
      regression of neurological manifestations in neuronopathic forms (types 2 and 3).
      SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders
      Group Inborn Errors of Metabolism Trials Register which comprises 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 of the Group's Haemoglobinopathies Trials Register: 19 January
      2017.We also searched the websites: www.clinicaltrials.gov; WHO International
      Clinical Trials Registry Platform portal and www.genzymeclinicalresearch.com.
      Date of most recent search of these sites: 02 March 2017. SELECTION CRITERIA: All
      randomised, quasi-randomised and controlled clinical trials comparing stem cell
      transplantation with enzyme replacement therapy, substrate reduction therapy,
      symptomatic treatment or no treatment in people with Gaucher disease of all ages.
      DATA COLLECTION AND ANALYSIS: We independently assessed trials for inclusion,
      however, no relevant trials were identified. MAIN RESULTS: Thirty two trials were
      identified by the searches; however, these were not suitable for inclusion in the
      review. AUTHORS' CONCLUSIONS: HSCT is a form of treatment that offers the
      potential of permanent cure. However, there are no clinical trials that have
      assessed the safety and efficacy of this treatment in comparison to other
      conservative measures (enzyme replacement therapy, substrate reduction therapy)
      now in use.There are no trials included in the review and we have not identified
      any relevant trials up to March 2017. We therefore do not plan to update this
      review until new trials are published.

PMID- 29044483
TI  - Hyperbaric vs. isobaric bupivacaine for spinal anaesthesia for elective caesarean
      section: a Cochrane systematic review.
AB  - Both isobaric and hyperbaric bupivacaine have been used for spinal anaesthesia
      for elective caesarean section, but it is not clear if one is better than the
      other. The primary objective of this systematic review was to determine the
      effectiveness and safety of hyperbaric bupivacaine compared with isobaric
      bupivacaine administered during spinal anaesthesia for elective caesarean
      section. We included 10 studies with 614 subjects in the analysis. There was no
      evidence of differences either in the risk of conversion to general anaesthesia,
      with a relative risk (95%CI) of 0.33 (0.09-1.17) (very low quality of evidence),
      or in the need for supplemental analgesia, the relative risk (95%CI) being 0.61
      (0.26-1.41) (very low quality of evidence). There was also no evidence of a
      difference in the use of ephedrine, the amount of ephedrine used, nausea and
      vomiting, or headache. Hyperbaric bupivacaine took less time to reach a sensory
      block height of T4, with a mean difference (95%CI) of -1.06 min (-1.80 to -0.31).
      Due to the rarity of some outcomes, dose variability, use of adjuvant drugs and
      spinal technique used, future clinical trials should look into using adequate
      sample size to investigate the primary outcome of the need for supplemental
      analgesia.

PMID- 29044484
TI  - Meta-analysis of the impact of surgical approach on the grade of mesorectal
      excision in rectal cancer.
AB  - BACKGROUND: The subspecialization of colorectal surgeons, and improvements in the
      quality of mesorectal excision have revolutionized rectal cancer surgery. With
      the increasing use of minimally invasive techniques, the completeness of the
      mesorectal excision has been questioned. This study aimed to assess the
      pathological outcomes of open versus laparoscopic rectal resection. METHODS: A
      meta-analysis of RCTs was undertaken. The primary endpoint was the adequacy of
      the mesorectal excision. Secondary endpoints included circumferential resection
      margin and distance to resection margins. RESULTS: Four studies were included,
      reporting on 2319 patients; 972 (41.9 per cent) had open and 1347 (58.1 per cent)
      had laparoscopic resections. Meta-analysis of adequacy of the mesorectal excision
      showed a small difference in achieving an intact mesorectum in favour of open
      surgery (risk ratio (RR) 1.06, 95 per cent c.i. 1.02 to 1.10; P = 0.001).
      Superficial defects were more common in laparoscopic surgery (RR 0.70, 0.54 to
      0.89; P = 0.004). Deep mesorectal defects (RR 0.78, 0.51 to 1.20; P = 0.256),
      circumferential margin (CRM) positivity (RR 0.85, 0.62 to 1.16; P = 0.310), and
      distance to radial (mean difference (MD) -0.06, 95 per cent c.i. -0.10 to 0.23; P
      = 0.443) and distal (MD 0.03, -0.06 to 0.12; P = 0.497) margins were all similar.
      A complete resection (intact mesorectum, negative CRM and distal margin) was
      achieved in 350 of 478 patients (73.2 per cent) in the laparoscopic group and 372
      of 457 (81.4 per cent) in the open group (risk difference (RD) 8 (95 per cent
      c.i. 3 to 13) per cent; P = 0.003). However, an acceptable mesorectum (intact or
      superficial defects only) was present in 1254 of 1308 (95.9 per cent) and 916 of
      949 (96.5 per cent) in the laparoscopic and open groups respectively (RD 1 (-1 to
      3) per cent; P = 0.263). CONCLUSION: Small differences in mesorectal quality were
      evident between open and laparoscopic rectal resections. This may be attributable
      to use of laparoscopic instruments; however, to date minor defects have not
      affected oncological outcomes.

PMID- 29044486
TI  - Spanish translation section.

PMID- 29044487
TI  - The challenges of surgical research in children.

PMID- 29044488
TI  - Randomized feasibility trial of replacing or discarding the nail plate after nail
      bed repair in children.
AB  - BACKGROUND: Nail-bed injuries are the most common hand injury in children.
      Surgical dogma is to replace the nail plate after repairing the nail bed. Recent
      evidence suggests this might increase infection rates and returns to clinic. The
      aim of this feasibility trial was to inform the design and conduct of a
      definitive trial comparing replacing or discarding the nail plate after nail-bed
      repair. METHODS: This study recruited participants from four hand units in the UK
      between April and July 2015. Participants were children under the age of 16 years
      with a nail-bed injury requiring surgery. They were randomized to either having
      the nail plate replaced or discarded after nail-bed repair. The follow-up method
      was also allocated randomly (postal versus clinic). Information was collected on
      complications at 2 weeks and 30 days, and on nail-plate appearance at 4 months
      using the Zook classification. Two possible approaches to follow-up were also
      piloted and compared. RESULTS: During the recruitment phase, there were 156
      potentially eligible children. Sixty were randomized in just over 3 months using
      remote web-based allocation. By 2 weeks, there were two infections, both in
      children with replaced nail plates. The nail-replaced group also experienced more
      complications. There was no evidence of a difference in return rates between
      postal and clinic follow-up. CONCLUSION: Recruitment was rapid and nail-bed
      repair appeared to have low complication and infection rates in this pilot trial.
      The findings have led to revision of the definitive trial protocol, including the
      mode and timing of follow-up, and modification of the Zook classification.

PMID- 29044489
TI  - Molecular analysis and genotype-phenotype correlation of Diamond-Blackfan anemia.
AB  - Diamond-Blackfan anemia (DBA) features hypoplastic anemia and congenital
      malformations, largely caused by mutations in various ribosomal proteins. The aim
      of this study was to characterize the spectrum of genetic lesions causing DBA and
      identify genotypes that correlate with phenotypes of clinical significance.
      Seventy-four patients with DBA from across Canada were included. Nucleotide-level
      mutations or large deletions were identified in 10 ribosomal genes in 45 cases.
      The RPS19 mutation group was associated with higher requirement for chronic
      treatment for anemia than other DBA groups. Patients with RPS19 mutations,
      however, were more likely to maintain long-term corticosteroid response without
      requirement for further chronic transfusions. Conversely, patients with RPL11
      mutations were less likely to need chronic treatment. Birth defects, including
      cardiac, skeletal, hand, cleft lip or palate and genitourinary malformations,
      also varied among the various genetic groups. Patients with RPS19 mutations had
      the fewest number of defects, while patients with RPL5 had the greatest number of
      birth defects. This is the first study to show differences between DBA genetic
      groups with regards to treatment. Previously unreported differences in the rate
      and types of birth defects were also identified. These data allow better patient
      counseling, a more personalized monitoring plan, and may also suggest
      differential functions of DBA genes on ribosome and extra-ribosomal functions.

PMID- 29044490
TI  - Reply to Cost-effectiveness calculations of human papillomavirus vaccination in
      Punjab may be flawed.

PMID- 29044491
TI  - Approaches to regional lymph node metastasis in patients with head and neck
      mucosal melanoma.
AB  - BACKGROUND: Mucosal melanomas in the head and neck region are most often located
      in the nasal cavity and paranasal sinuses. To the authors' knowledge, the
      prognostic effects of lymph node metastasis in patients with sinonasal mucosal
      melanoma (SNMM) have not been established. Therefore, the objective of the
      current study was to determine the effects of lymph node metastasis on survival.
      METHODS: The current study included 198 patients with SNMM who had been treated
      between 1985 and 2016 at The University of Texas MD Anderson Cancer Center in
      Houston. Patients' clinical and pathologic lymph node statuses were evaluated and
      characterized. A multivariate analysis was used to assess the associations
      between regional spread and survival outcomes. RESULTS: Therapeutic neck
      dissection was performed in 23 patients with SNMM (11.6%). Regional disease
      recurrence occurred in 7 of the patients who had lymph node metastasis at the
      time of presentation (30.4%) and in 30 of those who had N0 disease at the time of
      presentation (17.1%) (P = .15). Metastasis to the contralateral lymph nodes was
      present in 7 patients (3.5%). The 5-year disease-specific survival rate was 66%
      in patients with lymph node spread compared with 45% in patients with N0 status
      (P = .04, log-rank test). A multivariate analysis demonstrated that distant
      metastasis was the only variable found to be independently associated with both
      overall survival (hazard ratio, 2.96; 95% confidence interval, 1.54-6.95 [P =
      .01]) and disease-specific survival (hazard ratio, 3.32; 95% confidence interval,
      1.79-7.14 [P = 0.01]). CONCLUSIONS: The results of the current study demonstrated
      that lymph node status in patients with SNMM was not a significant predictor of
      outcome. This finding, together with the low incidence of lymph node metastases
      in patients with SNMM, suggests that elective treatment of the neck should be
      highly selective in this patient population. Cancer 2018;124:514-20. (c) 2017
      American Cancer Society.

PMID- 29044492
TI  - Cost-effectiveness calculations of human papillomavirus vaccination in Punjab may
      be flawed.

PMID- 29044493
TI  - Combining echo and natriuretic peptides to guide heart failure care in the
      outpatient setting: A position paper.
AB  - BACKGROUND: Chronic heart failure (HF) is a relevant and growing public health
      problem. Although the prognosis has recently improved, it remains a lethal
      disease, with a mortality that equals or exceeds that of many malignancies.
      Furthermore, chronic HF is costly, representing a large and growing drain on
      healthcare resources. METHODS: This narrative review is based on the material
      searched for and obtained via PubMed up to May 2017. The search terms we used
      were as follows: "heart failure, echocardiography, natriuretic peptides" in
      combination with "treatment, biomarkers, guidelines." RESULTS: Recent studies
      have supported the value of natriuretic peptides (NPs) and Doppler
      echocardiographic biomarkers of increased left ventricular (LV) filling pressures
      or pulmonary congestion as tools to scrutinize patients with impending clinically
      overt HF. Therefore, combination of pulsed-wave tissue and blood flow Doppler
      with NPs appears valuable in guiding HF management in the outpatient setting. In
      as much as both the echo and the plasma levels of NPs may reflect the presence of
      fluid overload and elevations of LV filling pressures, integrating NP and
      echocardiographic biomarkers with clinical findings may help the cardiologist to
      identify high-risk patients, that is to recognize whether a patient is stable or
      the condition is likely to evolve into decompensated HF, to optimize treatment,
      to improve the prognosis and to reduce rehospitalization. CONCLUSION: We
      discussed the rationale and the clinical significance of combining follow-up echo
      and NP assessment to guide management of ambulatory patients with chronic HF.

PMID- 29044494
TI  - Influence of Seasonal Pumping on Groundwater Sources and Flow System, Nagaoka
      Plain, Japan.
AB  - Intensive groundwater development in the urban area of the Nagaoka Plain, Japan,
      has induced changes in the pH and saturation index of calcite in groundwater. To
      account for these chemical changes, it is important to determine seasonal
      variations of recharge and the groundwater flow system in the aquifer. This study
      identified the sources and flow system of groundwater in this urban area by a
      comprehensive method using stable isotope data and a numerical groundwater model
      of the Nagaoka Plain. Stable isotope evidence shows that the groundwater is
      recharged by meteoric water originating from low-elevation areas rather than the
      mountains surrounding the plain. The water table in the study area is drawn down
      during the winter and recovers in the other seasons. Numerical modeling shows
      that discharge occurs primarily along the Shinano River during the recovery
      period, whereas discharge is centered in urbanized areas during the drawdown
      period, when a conical depression of the water table stimulates recharge from the
      immediate area. These results are indications of a local groundwater flow system,
      with its recharge area between the Shinano River and the urban areas, which is
      governed by intensive seasonal groundwater extraction.

PMID- 29044495
TI  - Urban particulate matter stimulation of human dendritic cells enhances priming of
      naive CD8 T lymphocytes.
AB  - Epidemiological studies have consistently shown associations between elevated
      concentrations of urban particulate matter (UPM) air pollution and exacerbations
      of asthma and chronic obstructive pulmonary disease, which are both associated
      with viral respiratory infections. The effects of UPM on dendritic cell (DC) 
      stimulated CD4 T lymphocytes have been investigated previously, but little work
      has focused on CD8 T-lymphocyte responses despite their importance in anti-viral
      immunity. To address this, we examined the effects of UPM on DC-stimulated naive
      CD8 T-cell responses. Expression of the maturation/activation markers CD83, CCR7,
      CD40 and MHC class I on human myeloid DCs (mDCs) was characterized by flow
      cytometry after stimulation with UPMin vitro in the presence/absence of
      granulocyte-macrophage colony-stimulating factor (GM-CSF). The capacity of these
      mDCs to stimulate naive CD8 T-lymphocyte responses in allogeneic co-culture was
      then assessed by measuring T-cell cytokine secretion using cytometric bead array,
      and proliferation and frequency of interferon-gamma (IFN-gamma)-producing T
      lymphocytes by flow cytometry. Treatment of mDCs with UPM increased expression of
      CD83 and CCR7, but not MHC class I. In allogeneic co-cultures, UPM treatment of
      mDCs enhanced CD8 T-cell proliferation and the frequency of IFN-gamma+ cells. The
      secretion of tumour necrosis factor-alpha, interleukin-13, Granzyme A and
      Granzyme B were also increased. GM-CSF alone, and in concert with UPM, enhanced
      many of these T-cell functions. The PM-induced increase in Granzyme A was
      confirmed in a human experimental diesel exposure study. These data demonstrate
      that UPM treatment of mDCs enhances priming of naive CD8 T lymphocytes and
      increases production of pro-inflammatory cytokines. Such UPM-induced stimulation
      of CD8 cells may potentiate T-lymphocyte cytotoxic responses upon concurrent
      airway infection, increasing bystander damage to the airways.

PMID- 29044497
TI  - Pediatric Headache and Sleep Disturbance: A Comparison of Diagnostic Groups.
AB  - OBJECTIVE: To examine whether sleep disturbance differs by headache diagnosis in
      a pediatric sample, and whether this effect remains when other factors affecting
      sleep are included. BACKGROUND: Primary headache disorders can be severe and
      disabling, impacting a child's functioning and quality of life. Many children and
      adolescents with chronic headaches also experience sleep difficulties, and there
      is likely a bidirectional relationship between headaches and sleep difficulties.
      Sleep problems may intensify functional and developmental difficulties in youth
      with chronic headaches. Despite this, research on sleep has largely been
      conducted only on those with migraines, with a dearth of studies including
      samples with tension-type headache (TTH) or new daily persistent-headache (NDPH).
      METHODS: This retrospective chart review included 527 patients, ages 7-17 years,
      with a primary headache diagnosis of migraine (n = 278), TTH (n = 157), and NDPH
      (n = 92). Patients completed measures of disability, anxiety, and depression and
      their parents completed measures of sleep disturbance. RESULTS: Sleep disturbance
      was greater in patients with TTH (10.34 +/- 5.94, P = .002) and NDPH (11.52 +/-
      6.40, P < .001) than migraine (8.31 +/- 5.89). Across patient groups, greater
      sleep disturbance was significantly associated with higher levels of functional
      disability (rs >= .16), anxiety (rs >= .30), and depression (rs >= .32).
      Additionally, higher pain levels were significantly associated with greater sleep
      disturbance among TTH patients (r = .23), with this association non-significant
      among the other headache groups. When simultaneously examining demographic, pain
      related, and emotional distress factors, older age, higher levels of disability
      and depression, and NDPH diagnosis were all significant predictors of greater
      sleep disturbance (r2  = .25). CONCLUSIONS: Assessment and treatment of sleep
      problems in pediatric patients with chronic headache is important with several
      contextual and headache diagnostic factors influencing the severity of sleep
      disturbance.

PMID- 29044496
TI  - NCCTG N0879 (Alliance): A randomized phase 2 cooperative group trial of
      carboplatin, paclitaxel, and bevacizumab +/- everolimus for metastatic melanoma.
AB  - BACKGROUND: Despite the success of immune checkpoint and targeted therapy, many
      patients with melanoma ultimately require further treatment. The combination of
      carboplatin, paclitaxel, and bevacizumab (CPB) has demonstrated promising
      activity in a single-arm study. In the current study, the authors performed a
      randomized phase 2 study to confirm efficacy and to determine whether adding
      everolimus would increase the activity of the combination. METHODS: Through the
      North Central Cancer Treatment Group, a total of 149 patients with unresectable
      AJCC 6th edition stage IV melanoma were randomized from May 2010 to May 2014 to
      either CPB or CPB with everolimus (CPBE). The primary endpoint was progression
      free survival (PFS), with secondary endpoints of overall survival (OS), response
      rate, and tolerability. RESULTS: The CPB and CPBE treatment arms were balanced
      with regard to age (median age: 59 years vs 58 years) and high lactate
      dehydrogenase (48% vs 51%), but were unbalanced with regard to sex (male sex: 72%
      vs 55%; P = .03). Overall, there was no difference noted with regard to PFS, with
      a median PFS of 5.6 months for CPB versus 5.1 months for CPBE (hazard ratio [HR],
      1.14; 95% confidence interval [95% CI], 0.81-1.62 [P = .44]), or for OS, with a
      median OS of 14.5 months for CPB versus 10.8 months for CPBE (HR, 1.16; 95% CI,
      0.84-1.84). The confirmed response rate was 13% for CPB and 23% for CPBE (P =
      .13). Toxicity was higher for CPBE compared with CPB (83% for grade 3 + and 14%
      for grade 4 + vs 63% for grade 3 + and 11% for grade 4+, respectively)
      (toxicities were graded using the Cancer Therapy Evaluation Program of the
      National Cancer Institute Common Terminology Criteria for Adverse Events [version
      4.0]). Common grade 3 + toxicities were neutropenia, leukopenia, and fatigue,
      which occurred in both treatment arms with comparable frequency. CONCLUSIONS:
      Both experimental arms demonstrated activity, with a PFS of >5 months. However,
      the addition of everolimus to CPB failed to improve outcomes, with increased
      toxicity noted. These findings replicate the moderate antitumor activity of CPB,
      with future development possibly in combination with targeted or immunotherapy.
      Cancer 2018;124:537-45. (c) 2017 American Cancer Society.

PMID- 29044498
TI  - Emerging Therapies for Congestive Heart Failure.
AB  - The treatment of atherosclerotic heart disease has improved remarkably over the
      last several decades; however, the outlook for patients with symptomatic
      congestive heart failure with reduced ejection fraction remains bleak. Current
      drug therapies target the neurohormonal activation that accompanies congestive
      heart failure, but do not address the fundamental pathology inherent in this
      condition-the loss of contractile capacity. Stem cell therapies offer the
      possibility of rectifying this deficiency and normalizing left ventricular
      dimensions and cardiac performance by regenerating novel contractile tissue,
      thereby reversing the negative remodeling that portends progressive left
      ventricular dysfunction, worsening symptoms, and ultimately cardiogenic shock.
      Here we review the promise of stem cell therapies in the treatment of heart
      failure with reduced ejection fraction, the current state of clinical
      developments, and briefly comment on the future of the field.

PMID- 29044499
TI  - Identification of the first homozygous 1-bp deletion in GDF9 gene leading to
      primary ovarian insufficiency by using targeted massively parallel sequencing.
AB  - Targeted massively parallel sequencing (TMPS) has been used in genetic diagnosis
      for Mendelian disorders. In the past few years, the TMPS has identified new and
      already described genes associated with primary ovarian insufficiency (POI)
      phenotype. Here, we performed a targeted gene sequencing to find a genetic
      diagnosis in idiopathic cases of Brazilian POI cohort. A custom SureSelectXT DNA
      target enrichment panel was designed and the sequencing was performed on Illumina
      NextSeq sequencer. We identified 1 homozygous 1-bp deletion variant (c.783delC)
      in the GDF9 gene in 1 patient with POI. The variant was confirmed and segregated
      using Sanger sequencing. The c.783delC GDF9 variant changed an amino acid
      creating a premature termination codon (p.Ser262Hisfs*2). This variant was not
      present in all public databases (ExAC/gnomAD, NHLBI/EVS and 1000Genomes).
      Moreover, it was absent in 400 alleles from fertile Brazilian women screened by
      Sanger sequencing. The patient's mother and her unaffected sister carried the
      c.783delC variant in a heterozygous state, as expected for an autosomal recessive
      inheritance. Here, the TMPS identified the first homozygous 1-bp deletion variant
      in GDF9. This finding reveals a novel inheritance pattern of pathogenic variant
      in GDF9 associated with POI, thus improving the genetic diagnosis of this
      disorder.

PMID- 29044500
TI  - Water and Salt Migration with Phase Change in Saline Soil during Freezing and
      Thawing Processes.
AB  - Water and salt transfer coupled with phase change may cause serious damage to
      engineering structures in saline soil regions. In this study, the migration of
      water and salt in silty clay collected from the Qinghai-Tibet Plateau is explored
      experimentally and numerically during freezing and thawing processes. The results
      revealed that there are significant differences in the variations of liquid water
      content and solution concentration for different initial salt contents, due to
      salt crystallization and dissolution. The temperature-induced water migration is
      determined by the soil properties, which can be well explained by the
      thermodynamics of mass transfer. The amount of salt migrated upward during
      cooling is slightly larger than that transported downward in the warming period,
      implying that salt may be accumulated in the surface soil after a large number of
      circulations and finally result in soil salinization.

PMID- 29044501
TI  - Authentication of Surveillance Videos: Detecting Frame Duplication Based on
      Residual Frame.
AB  - Nowadays, surveillance systems are used to control crimes. Therefore, the
      authenticity of digital video increases the accuracy of deciding to admit the
      digital video as legal evidence or not. Inter-frame duplication forgery is the
      most common type of video forgery methods. However, many existing methods have
      been proposed for detecting this type of forgery and these methods require high
      computational time and impractical. In this study, we propose an efficient inter
      frame duplication detection algorithm based on standard deviation of residual
      frames. Standard deviation of residual frame is applied to select some frames and
      ignore others, which represent a static scene. Then, the entropy of discrete
      cosine transform coefficients is calculated for each selected residual frame to
      represent its discriminating feature. Duplicated frames are then detected exactly
      using subsequence feature analysis. The experimental results demonstrated that
      the proposed method is effective to identify inter-frame duplication forgery with
      localization and acceptable running time.

PMID- 29044502
TI  - Factors associated with patients with gestational diabetes in Japan being at
      increased risk of requiring intensive care.
AB  - OBJECTIVE: To investigate factors associated with high-risk gestational diabetes
      (GDM) among patients with GDM. METHODS: The present retrospective study included
      women with singleton pregnancies diagnosed with GDM using International
      Association of Diabetes and Pregnancy Study Group criteria at a single tertiary
      perinatal care center in Japan between July 1, 2010, and October 31, 2014. High
      risk GDM was defined as patients who required at least 20 units of insulin
      therapy a day, delivering a large-for-gestational age neonate regardless of
      insulin therapy, or both. Maternal characteristics and diagnostic test results
      were investigated to identify associations with the high-risk criteria, and odds
      ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Among
      217 patients, 95 (43.8%) were categorized as high risk. After adjusting for
      confounders, a fasting plasma glucose level at diagnosis of at least 4.66 mmol/L
      (adjusted OR 2.88, 95% CI 1.51-5.58) and pre-pregnancy body mass index
      (calculated as weight in kilograms divided by the square of height in meters) of
      at least 24 (adjusted OR 3.27, 95% CI 1.60-6.90) were independently associated
      with meeting the high-risk criteria. CONCLUSION: Among Japanese patients with
      GDM, pre-pregnancy body mass index and fasting plasma glucose levels could be
      used to identify high-risk patients requiring intensive care during pregnancy.

PMID- 29044503
TI  - Clinical significance of programmed cell death-ligand 1 expression and the immune
      microenvironment at the invasive front of colorectal cancers with high
      microsatellite instability.
AB  - Immunotherapy is reportedly effective in colorectal cancers (CRCs) with high
      microsatellite instability (MSI-H); however, the specific cell types that respond
      to immune checkpoint therapy are unclear. Herein, we aimed to examine the
      expression of programmed cell death-ligand 1 (PD-L1) and related proteins in MSI
      H and microsatellite-stable (MSS) CRCs to investigate the immune microenvironment
      at the tumor's invasive front. The MSI status was retrospectively assessed in 499
      patients undergoing surgical resection of primary CRC; of these, 48 were
      classified as MSI-H. Propensity score matching was performed, and tissues from 36
      and 37 patients with MSI-H and MSS CRCs, respectively, were immunohistochemically
      evaluated for PD-L1, PD-1, CD8 and CD68. PD-L1 expression was evaluated
      separately for tumor cells (PD-L1 [T]) and tumor-infiltrating myeloid cells in
      the stroma (PD-L1 [I]). PD-L1 (T) was positive in only 5.4% and 36.1% of MSS and
      MSI-H CRCs, while PD-L1 (I) was positive in 27% and 72.2% of these CRCs,
      respectively. The PD-L1 (T) and PD-L1 (I) expression levels in MSI-H CRCs
      significantly correlated with poor differentiation, lymphatic invasion and
      vascular invasion (p < 0.05), and with early-stage adenocarcinoma and high
      budding grade (p < 0.05), respectively. Significantly more PD-L1 (I), CD8
      positive cells and CD68-positive macrophages were present at the invasive front
      than in the central tumor in MSI-H CRCs (p < 0.005). PD-L1 was expressed on both
      tumor cells and CD68/CD163-positive (M2) macrophages at the invasive front of MSI
      H CRCs. In conclusion, PD-L1-positive tumor cells and M2-type tumor-associated
      macrophages may contribute to tumor invasion and immune escape at the invasive
      front.

PMID- 29044504
TI  - A low-frequency haplotype spanning SLX4/FANCP constitutes a new risk locus for
      early-onset breast cancer (<60 years) and is associated with reduced DNA repair
      capacity.
AB  - Only a fraction of breast cancer (BC) cases can be yet explained by mutations in
      genes or genomic variants discovered in linkage, genome-wide association and
      sequencing studies. The known genes entailing medium or high risk for BC are
      strongly enriched for a function in DNA double strand repair. Thus, aiming at
      identifying low frequency variants conferring an intermediate risk, we here
      investigated 17 variants (MAF: 0.01-0.1) in 10 candidate genes involved in DNA
      repair or cell cycle control. In an exploration cohort of 437 cases and 1189
      controls, we show the variant rs3810813 in the SLX4/FANCP gene to be
      significantly associated with both BC (<=60 years; OR = 2.6(1.6-3.9), p = 1.6E
      05) and decreased DNA repair capacity (<=60 years; beta = 37.8(17.9-57.8), p =
      5.3E-4). BC association was confirmed in a verification cohort (N = 2441). Both
      associations were absent from cases diagnosed >60 years and stronger the earlier
      the diagnosis. By imputation we show that rs3810813 tags a haplotype with 5
      additional variants with the same allele frequency (R2  > 0.9), and a pattern of
      association very similar for both phenotypes (cases <60 years, p < 0.001, the
      Bonferroni threshold derived from unlinked variants in the region). In young
      cases (<=60 years) carrying the risk haplotype, micronucleus test results are
      predictive for BC (AUC > 0.9). Our findings propose a risk variant with high
      penetrance on the haplotype spanning SLX4/FANCP to be functionally associated to
      BC predisposition via decreased repair capacity and suggest this variant is
      carried by a fraction of these haplotypes that is enriched in early onset BC
      cases.

PMID- 29044505
TI  - Diagnostic pathology of early systemic cancer: ERBB2 gene amplification in single
      disseminated cancer cells determines patient survival in operable esophageal
      cancer.
AB  - Early metastatic dissemination and evolution of disseminated cancer cells (DCCs)
      outside the primary tumor is one reason for the failure of adjuvant therapies
      because it generates molecular genotypes and phenotypes different from primary
      tumors, which still underlie therapy decisions. Since ERBB2 amplification in
      esophageal DCCs but not in primary tumor cells predict outcome, we aimed to
      establish an assay with diagnostic reliability for single DCCs or circulating
      tumor cells. For this, we evaluated copy number alterations of more than 600
      single DCCs from multiple cancer types to define reference regions suitable for
      quantification of target regions, such as ERBB2. We then compared ERBB2
      quantitative PCR (qPCR) measurements with fluorescent in situ hybridization
      (FISH) data of various breast cancer cell lines and identified the aberration
      calling threshold. The method was applied to two independent cohorts of
      esophageal cancer patients from Hamburg (n = 59) and Dusseldorf (n = 53). We
      found a high correlation between the single cell qPCR assay and the standard FISH
      assay (R = 0.98) and significant associations between amplification and survival
      for both patient cohorts (Hamburg (HH), p = 0.033; Dusseldorf (D), p = 0.052;
      pooled HH + D, p = 0.002) when applied to DCCs of esophageal cancer patients.
      Detection of a single ERBB2-amplified DCC was the most important risk factor for
      death from esophageal cancer (relative risk = 4.22; 95% CI = 1.91-9.32; p <
      0.001). In our study, we detected ERBB2-amplified cells in 7% of patients. These
      patients could benefit from anti-ERBB2 targeting therapies.

PMID- 29044506
TI  - A Retrospective Study of the Investigation of Homicidal Childhood Asphyxial
      Deaths.
AB  - As one of the leading causes of traumatic deaths in newborns, infants, and young
      children, there is no anatomic or microscopic feature that is pathognomonic for
      asphyxial deaths. Instead, pathologists rely on investigation information,
      including confessions and/or witness statements, and potential evidence at the
      scene. Twenty cases of homicidal newborn, infant, and young children asphyxial
      deaths were reviewed, which included death and police investigation reports and
      autopsy reports, as well as histology slides of lung sections. This series of
      homicidal asphyxial deaths highlight that, in a vast majority of such cases, the
      final cause and manner of death rulings are dependent on confession by the
      perpetrator. Furthermore, this series highlights the possible role of histology
      to help forensic pathologists better certify asphyxial deaths. Finally, this
      series emphasizes important investigation points and considerations at autopsy
      during the investigation of asphyxial deaths in newborns, infants, and young
      children.

PMID- 29044507
TI  - TIEG and estrogen modulate SOST expression in the murine skeleton.
AB  - TIEG knockout (KO) mice exhibit a female-specific osteopenic phenotype and
      altered expression of TIEG in humans is associated with osteoporosis. Gene
      expression profiling studies identified sclerostin as one of the most highly up
      regulated transcripts in the long bones of TIEG KO mice relative to WT
      littermates suggesting that TIEG may regulate SOST expression. TIEG was shown to
      substantially suppress SOST promoter activity and the regulatory elements through
      which TIEG functions were identified using promoter deletion and chromatin
      immunoprecipitation assays. Knockdown of TIEG in IDG-SW3 osteocyte cells using
      shRNA and CRISPR-Cas9 technology resulted in increased SOST expression and
      delayed mineralization, mimicking the results obtained from TIEG KO mouse bones.
      Given that TIEG is an estrogen regulated gene, and as changes in the hormonal
      milieu affect SOST expression, we performed ovariectomy (OVX) and estrogen
      replacement therapy (ERT) studies in WT and TIEG KO mice followed by miRNA and
      mRNA sequencing of cortical and trabecular compartments of femurs. SOST
      expression levels were considerably higher in cortical bone compared to
      trabecular bone. In cortical bone, SOST expression was increased following OVX
      only in WT mice and was suppressed following ERT in both genotypes. In contrast,
      SOST expression in trabecular bone was decreased following OVX and significantly
      increased following ERT. Interestingly, a number of miRNAs that are predicted to
      target sclerostin exhibited inverse expression levels in response to OVX and ERT.
      These data implicate important roles for TIEG and estrogen-regulated miRNAs in
      modulating SOST expression in bone.

PMID- 29044508
TI  - Differentially regulated gene expression in quiescence versus senescence and
      identification of ARID5A as a quiescence associated marker.
AB  - In multicellular organisms majority of the cells remain in a non-dividing states
      of either quiescence (reversible) or senescence (irreversible). In the present
      study, gene expression signatures unique to quiescence and senescence were
      identified using microarray in osteosarcoma cell line, U2OS. It was noted that
      certain genes and pathways like NOD pathway was shared by both the growth arrest
      conditions. A major highlight of the present study was increased expression of
      number of chemokines and cytokines in both quiescence and senescence. While
      senescence-associated secretory phenotype (SASP) is well known, the quiescence
      associated secretory phenotype (QASP) is relatively unknown and appeared novel in
      this study. ARID5A, a subunit of SWI/SNF complex was identified as a quiescence
      associated gene. The endogenous expression of ARID5A increased during serum
      starved condition of quiescence. Overexpression of ARID5A resulted in more number
      of cells in G0/G1 phase of cell cycle. Further ARID5A overexpressing cells when
      subjected to serum starvation showed a pronounced secretory phenotype. Overall,
      the present work has identified gene expression signatures which can distinguish
      quiescence from senescence.

PMID- 29044509
TI  - Comprehensive transcriptome analysis of fluid shear stress altered gene
      expression in renal epithelial cells.
AB  - Renal epithelial cells are exposed to mechanical forces due to flow-induced shear
      stress within the nephrons. Shear stress is altered in renal diseases caused by
      tubular dilation, obstruction, and hyperfiltration, which occur to compensate for
      lost nephrons. Fundamental in regulation of shear stress are primary cilia and
      other mechano-sensors, and defects in cilia formation and function have profound
      effects on development and physiology of kidneys and other organs. We applied RNA
      sequencing to get a comprehensive overview of fluid-shear regulated genes and
      pathways in renal epithelial cells. Functional enrichment-analysis revealed TGF
      beta, MAPK, and Wnt signaling as core signaling pathways up-regulated by shear.
      Inhibitors of TGF-beta and MAPK/ERK signaling modulate a wide range of
      mechanosensitive genes, identifying these pathways as master regulators of shear
      induced gene expression. However, the main down-regulated pathway, that is,
      JAK/STAT, is independent of TGF-beta and MAPK/ERK. Other up-regulated cytokine
      pathways include FGF, HB-EGF, PDGF, and CXC. Cellular responses to shear are
      modified at several levels, indicated by altered expression of genes involved in
      cell-matrix, cytoskeleton, and glycocalyx remodeling, as well as glycolysis and
      cholesterol metabolism. Cilia ablation abolished shear induced expression of a
      subset of genes, but genes involved in TGF-beta, MAPK, and Wnt signaling were
      hardly affected, suggesting that other mechano-sensors play a prominent role in
      the shear stress response of renal epithelial cells. Modulations in signaling due
      to variations in fluid shear stress are relevant for renal physiology and
      pathology, as suggested by elevated gene expression at pathological levels of
      shear stress compared to physiological shear.

PMID- 29044511
TI  - Second-trimester levels of fetoplacental hormones among women with placenta
      accreta spectrum disorders.

PMID- 29044510
TI  - Disrespect and abuse during childbirth in fourteen hospitals in nine cities of
      Peru.
AB  - OBJECTIVE: To assess the prevalence of disrespect and abuse during childbirth and
      its associated factors in Peru. METHODS: In an observational cross-sectional
      study, women were surveyed within 48 hours of live delivery at 14 hospitals
      located in nine Peruvian cities between April and July 2016. The survey was based
      on seven categories of disrespect and abuse proposed by Bowser and Hill. To
      evaluate factors associated with each category, prevalence ratios (PRs) and 95%
      confidence intervals (CIs) were calculated using adjusted Poisson models with
      robust variances. RESULTS: Among 1528 participants, 1488 (97.4%) had experienced
      at least one category of disrespect and abuse. Frequency of abandonment of care
      was increased with cesarean delivery (PR 1.27, 95% CI 1.03-1.57) but decreased in
      the jungle region (PR 0.27, 0.14-0.53). Discrimination was associated with the
      jungle region (PR 5.67, 2.32-13.88). Physical abuse was less frequent with
      cesarean than vaginal delivery (PR 0.23, 0.11-0.49). The prevalences of
      abandonment of care (PR 0.42, 0.29-0.60), non-consented care (PR 0.70, 0.57
      0.85), discrimination (PR 0.40, 0.19-0.85), and non-confidential care (PR 0.71,
      0.55-0.93) were decreased among women who had been referred. CONCLUSION: Nearly
      all participants reported having experienced at least one category of disrespect
      and abuse during childbirth care, which was associated with type of delivery,
      being referred, and geographic region.

PMID- 29044512
TI  - Differences in definitive endoderm induction approaches using growth factors and
      small molecules.
AB  - Definitive endoderm (DE) is the first stage of human pluripotent stem cell (hPSC)
      differentiation into hepatocyte-like cells. Developing human liver cell models
      for pharmaceutical applications is highly demanding. Due to the vast number of
      existing protocols to generate DE cells from hPSCs, we aimed to compare the
      specificity and efficiency of selected published differentiation conditions. We
      differentiated two hPSC lines (induced PSC and embryonic stem cell) to DE cells
      on Matrigel matrix using growth factors (Activin A and Wnt-3a) and small
      molecules (sodium butyrate and IDE 1) in different combinations. By studying
      dynamic changes during 6 days in cell morphology and the expression of markers
      for pluripotency, DE, and other germ layer lineages, we found that Activin A is
      essential for DE differentiation, while Wnt-3a and sodium butyrate are
      dispensable. Although sodium butyrate exerted rapid DE differentiation kinetics,
      it caused massive cell death and could not generate sufficient cells for further
      differentiation and applications. We further discover that IDE 1 could not induce
      DE as reported previously. Hereby, we compared different conditions for DE
      induction and found an effective six day-protocol to obtain DE cells for the
      further differentiation and applications.

PMID- 29044513
TI  - Chemicals released by predation increase the growth rate of yellow perch, Perca
      flavescens.
AB  - Water-soluble factors associated with walleye Sander vitreus predation on either
      yellow perch Perca flavescens or fathead minnows Pimephales promelas markedly
      increased the growth rate of P. flavescens. The findings suggest that P.
      flavescens possess an inducible growth-promoting mechanism regulated by water
      born chemicals. It may be possible to increase the growth rate of farm-raised P.
      flavescens by manipulating this system.

PMID- 29044514
TI  - CCDC6: the identity of a protein known to be partner in fusion.
AB  - Coiled Coil Domain Containing 6 gene, CCDC6, was initially isolated as part of a
      tumorigenic DNA originated by the fusion of CCDC6 with the tyrosine kinase of RET
      receptor, following a paracentric inversion of chromosome 10. For a long time,
      CCDC6 has been considered as an accidental partner of the RET protooncogene,
      providing the promoter and the first 101 aa necessary for the constitutive
      activation of the oncogenic Tyrosine Kinase (TK) RET in thyroid cells. With the
      advent of more refined diagnostic tools and bioinformatic algorithms, an
      exponential growth in fusion genes discoveries has allowed the identification of
      CCDC6 as partner of genes other than RET in different tumor types. CCDC6 gene
      product has a proper role in sustaining the DNA damage checkpoints in response to
      DNA damage. The inactivation of CCDC6 secondary to chromosomal rearrangements or
      gene mutations could enhance tumor progression by impairing the apoptotic
      response upon the DNA damage exposure, contributing to the generation of radio-
      and chemoresistance. Preclinical studies indicate that the attenuation of CCDC6
      in cancer, while conferring a resistance to cisplatinum, sensitizes the cancer
      cells to the small molecule inhibitors of Poly (ADP-ribose) polymerase (PARP1/2)
      with a synthetic lethal effect. Several CCDC6 mutations and gene rearrangements
      have been described so far in different types of cancer and CCDC6 may represent a
      possible predictive biomarker of tumor resistance to the conventional anticancer
      treatments. Nevertheless, the detection of a CCDC6 impairment in cancer patients
      may help to select, in future clinical trials, those patients who could benefit
      of PARP-inhibitors treatment alone or in combination with other treatments.

PMID- 29044516
TI  - Gonadotropin-inhibitory hormone in the flatfish, Solea senegalensis: Molecular
      cloning, brain localization and physiological effects.
AB  - Recently, gonadotropin-inhibitory hormone (GnIH) has emerged as an important
      regulator of reproduction in birds and mammals. This RFamide neuropeptide has
      neuromodulatory functions and controls the synthesis and/or release of
      gonadotropin-releasing hormone (GnRH) and gonadotropins. Although teleosts
      represent about half of all living vertebrates, scientific and technological
      advances on the Gnih system in fish are scarce, contradictory, and inconclusive.
      Research on the fish Gnih system appears necessary to better clarify its role in
      the neuroendocrine and environmental control of vertebrate reproduction. In this
      study, we cloned a full-length sequence for the Gnih precursor of a flatfish, the
      Senegalese sole, coding for three putative Gnih peptides (ssGnih). We also
      generated specific antibodies against these ssGnih peptides, and used them to
      localize Gnih cells and their projections in the brain and pituitary. The
      expression of gnih was particularly evident in the diencephalon, but also in the
      olfactory bulbs/cerebral hemispheres, optic tectum/tegmentum, retina, and
      pituitary. The three antibodies used provided consistent results and showed that
      ssGnih-immunoreactive perikarya were present in the olfactory bulbs, ventral
      telencephalon, caudal preoptic area, dorsal tegmentum and rostral
      rhombencephalon, and their fibers innervated the brain and pituitary profusely.
      Intramuscular injection of ssGnih-3 provoked a significant reduction in gnrh-3
      and lh expression, whereas ssGnih-2 treatment did not affect transcript levels of
      the main reproductive genes. Our results reveal the existence of a functional
      Gnih system in the sole brain, profusely innervating different brain areas and
      the pituitary gland, which could represent an important factor in the
      neuroendocrine control of flatfish reproduction.

PMID- 29044515
TI  - The human PKP2/plakophilin-2 gene is induced by Wnt/beta-catenin in normal and
      colon cancer-associated fibroblasts.
AB  - Colorectal cancer results from the malignant transformation of colonic epithelial
      cells. Stromal fibroblasts are the main component of the tumour microenvironment,
      and play an important role in the progression of this and other neoplasias.
      Wnt/beta-catenin signalling is essential for colon homeostasis, but aberrant,
      constitutive activation of this pathway is a hallmark of colorectal cancer. Here
      we present the first transcriptomic study on the effect of a Wnt factor on human
      colonic myofibroblasts. Wnt3A regulates the expression of 1,136 genes, of which
      662 are upregulated and 474 are downregulated in CCD-18Co cells. A set of genes
      encoding inhibitors of the Wnt/beta-catenin pathway stand out among those induced
      by Wnt3A, which suggests that there is a feedback inhibitory mechanism. We also
      show that the PKP2 gene encoding the desmosomal protein Plakophilin-2 is a novel
      direct transcriptional target of Wnt/beta-catenin in normal and colon cancer
      associated fibroblasts. PKP2 is induced by beta-catenin/TCF through three binding
      sites in the gene promoter and one additional binding site located in an enhancer
      20 kb upstream from the transcription start site. Moreover, Plakophilin-2
      antagonizes Wnt/beta-catenin transcriptional activity in HEK-293T cells, which
      suggests that it may act as an intracellular inhibitor of the Wnt/beta-catenin
      pathway. Our results demonstrate that stromal fibroblasts respond to canonical
      Wnt signalling and that Plakophilin-2 plays a role in the feedback control of
      this effect suggesting that the response to Wnt factors in the stroma may
      modulate Wnt activity in the tumour cells.

PMID- 29044517
TI  - CircFUT10 reduces proliferation and facilitates differentiation of myoblasts by
      sponging miR-133a.
AB  - Circular RNAs (circRNAs) have been identified in various tissues and cell types
      from human, monkey, porcine, and mouse. However, knowledge on circRNAs in bovine
      muscle development is limited. We downloaded and analyzed the circRNAs sequencing
      data of bovine skeletal muscle tissue, and further characterized the role of a
      candidate circRNA (circFUT10) in muscle development. Quantitative real-time PCR
      (qPCR) and Western blot assays were used to confirm the expression of genes
      involved in myoblasts differentiation and proliferation. Flow cytometry was
      performed to assess cell cycle distribution and cell apoptosis. EdU incorporation
      and CCK-8 assay were performed to demonstrate cell proliferation. We demonstrated
      that circFUT10 was highly (but differentially) expressed in embryonic and adult
      skeletal muscle tissue. circFUT10 induced bovine primary myoblasts
      differentiation and increased the expression of MyoD, MyoG, and MyhC in mRNA and
      protein levels. circFUT10 increased the number of myoblasts in the G0/G1 phase of
      the cell cycle, and decreased the proportion of cells in the S-phase. circFUT10
      inhibited the proliferation of myoblasts and promoted them apoptosis. Via a
      luciferase screening assay, circFUT10 is observed to sponge to miR-133a with
      three potential binding sites. Specifically, we show that circFUT10 regulated
      myoblasts differentiation and cell survival by directly binding to miR-133a and
      inhibiting miR-133a activity. Modulation of circFUT10 expression in muscle tissue
      may emerge as a potential target in breeding strategies attempting to control
      muscle development in cattle.

PMID- 29044518
TI  - Characterization of an Olive Flounder Bone Gelatin-Zinc Oxide Nanocomposite Film
      and Evaluation of Its Potential Application in Spinach Packaging.
AB  - : Olive flounder bone gelatin (OBG) was used for a film base material in this
      study. In addition, zinc oxide nanoparticles (ZnO) were incorporated into the OBG
      film to prepare a nanocomposite film and to impart antimicrobial activity to it.
      The tensile strength of the OBG film increased by 6.62 MPa, and water vapor
      permeability and water solubility decreased by 0.93 * 10-9 g/m s Pa and 13.79%,
      respectively, by the addition of ZnO to the OBG film. In particular, the OBG-ZnO
      film exhibited antimicrobial activity against Listeria monocytogenes. To
      investigate the applicability of the OBG-ZnO packaging film, fresh spinach was
      wrapped in this film and stored for a week. The results indicated that the OBG
      ZnO film showed antimicrobial activity against L. monocytogenes inoculated on
      spinach without affecting the quality of spinach, such as vitamin C content and
      color. Thus, the OBG-ZnO nanocomposite film can be applied as an efficient
      antimicrobial food packaging material. PRACTICAL APPLICATION: As a base material
      of edible films, gelatin was extracted from olive flounder bone, which is fish
      processing by-product. Olive flounder bone gelatin (OBG) nanocomposite films were
      prepared with zinc oxide nanoparticles (ZnO). For an application to antimicrobial
      packaging, spinach was wrapped with the OBG-ZnO nanocomposite film.

PMID- 29044519
TI  - Unhealthy dependency in victims and perpetrators of child maltreatment: A meta
      analytic review.
AB  - OBJECTIVE: Theoretical conceptualizations of interpersonal dependency and
      dependent personality disorder suggest that (a) high levels of dependency in
      parents may increase risk for perpetration of child abuse and neglect and (b)
      children who are victimized may show elevated levels of dependency later in life.
      This study used meta-analytic techniques to examine these hypothesized links.
      METHOD: A systematic search of psychological and medical online databases
      revealed 14 published studies (21 effect sizes) examining the link between
      parental dependency and perpetration of abuse or neglect (overall N of
      perpetrators = 1,321), and 14 published studies (25 effect sizes) assessing
      dependency in victims of child abuse and neglect (overall N of victims = 38,265).
      RESULTS: The dependency-abuse effect size (d) for perpetrators collapsed across
      all moderating variables was 0.36, which is considered to be in the medium range.
      The dependency-victimization effect size (d) collapsed across all moderating
      variables was 0.29, also a medium effect size. CONCLUSION: These results support
      and extend analyses of the relationship between dependency and child
      maltreatment, and suggest that dependency may be both a precipitant of child
      maltreatment and consequence of victimization. Theoretical and clinical
      implications are discussed, with suggestions for further research outlined.

PMID- 29044520
TI  - Quercetin protects against radiocontrast medium toxicity in human renal proximal
      tubular cells.
AB  - Radiocontrast media (RCM)-induced acute kidney injury (CI-AKI) is a major
      clinical problem whose pathophysiology is not well understood. Direct toxic
      effects on renal cells, possibly mediated by reactive oxygen species, have been
      postulated as contributing to CI-AKI. We investigated the effect of quercetin on
      human renal proximal tubular (HK-2) cells treated with the radiocontrast medium
      (RCM) sodium diatrizoate. Quercetin is the most widely studied flavonoid, and the
      most abundant flavonol present in foods. It has been suggested to have many
      health benefits, including angioprotective properties and anti-cancer effects.
      These beneficial effects have been attributed to its antioxidant properties and
      its ability to modulate cell signaling pathways. Incubation of HK-2 cells with
      100 MUM quercetin caused a decrease in cell viability and pre-treatment of HK-2
      cells with 100 MUM quercetin followed by incubation with 75 mgI/ml sodium
      diatrizoate for 2 hr caused a decrease in cell viability which was worse than in
      cells treated with diatrizoate alone. However, further incubation of the cells
      (for 22 hr) after removal of the diatrizoate and quercetin caused a recovery in
      cell viability in those cells previously treated with quercetin + diatrizoate and
      quercetin alone. Analysis of signaling molecules by Western blotting showed that
      in RCM-treated cells receiving initial pre-treatment with quercetin, followed by
      its removal, an increase in phosphorylation of Akt (Ser473), pSTAT3 (Tyr705), and
      FoxO3a (Thr32) as well as an induction of Pim-1 and decrease in PARP1 cleavage
      were observed. Quercetin may alleviate the longer-term toxic effects of RCM
      toxicity and its possible beneficial effects should be further investigated.

PMID- 29044521
TI  - Influence of tongue brushing and scraping on the oral microflora of periodontitis
      patients.
AB  - OBJECTIVE: To examine the effect of tongue cleaning with a tongue scraper (TS) or
      toothbrush (TB) in patients with periodontitis. BACKGROUND: The tongue is a
      possible reservoir for bacterial (re)colonization of the periodontal tissues in
      patients with periodontitis. To date, it is not known what the influence of
      tongue cleaning is on the tongue coating of patients with periodontitis. MATERIAL
      AND METHODS: Eighteen systemically healthy, untreated moderate to severe adult
      patients with periodontitis with some degree of tongue coating were randomly
      assigned to the use of a TS or TB for cleaning the tongue. Microbial load of the
      saliva and tongue dorsum, amount of tongue coating and patient perception about
      tongue cleaning were studied at baseline and 2 weeks later. RESULTS: Two weeks of
      tongue cleaning with either a TB or a TS, did not influence the microbiological
      counts, neither in the saliva, nor in the tongue coating, even though tongue
      coating was significantly less. The patients themselves experienced no
      differences in breath odour or taste sensation after 2 weeks of tongue cleaning;
      however, they felt that their tongue was cleaner at the end of the study compared
      to baseline. No differences could be detected between the uses of a TS vs a TB.
      CONCLUSION: In patients with periodontitis, tongue cleaning does not influence
      the bacterial load in the saliva or on the tongue dorsum.

PMID- 29044522
TI  - An Automated Two-Dimensional Form Registration Method for Osteological Pair
      Matching.
AB  - This study introduces an automated method for osteological pair-matching using
      two-dimensional outline form data extracted from photographs. A procedure for
      acquiring photographs that improve the differentiation of specimens from the
      background is presented along with an extraction procedure that allows the
      capture of form data from photographs. The raw form data are used in a two
      dimensional registration procedure, which combines iterative closest point, K
      nearest neighbor search, and iterations around an estimated mean. Form data are
      used in optimized distance calculations that minimize true-pair difference and
      maximize false-pair difference. The sample consists of 122 calcanei and 110 tali
      from the UI-Stanford collection. Performance statistics are provided for the
      maximum and average Segmented-Hausdorff, Hausdorff, and Procrustes distances to
      show the comparative statistical results for matching. Results indicate 98.36%
      and 98.2% accuracy in pinpointing true-pairs for the calcanei and tali,
      respectively, using a shortlist of one-lowest-distance.

PMID- 29044523
TI  - Osseointegration of zirconia and titanium implants in a rabbit tibiae model
      evaluated by microtomography, histomorphometry and fluorochrome labeling
      analyses.
AB  - OBJECTIVES: This study compares the osseointegration of machined-zirconia
      implants containing yttria (M-Y-TZP) with machined (M-Ti) and resorbable blast
      media (RBM-Ti) titanium implants. MATERIAL AND METHODS: M-Y-TZP, M-Ti and RBM-Ti
      implants were randomly placed in rabbit tibiae. Fluorochrome bone labels
      (tetracycline, alizarin and calcein) were administered at different time periods.
      After 8 weeks, osseointegration was evaluated in terms of bone-to-implant contact
      (BIC), new bone area (nBA), remaining cortical bone area (rBA) and temporal
      quantification of fluorochromes, using micro-CT and histomorphometric analyses.
      RESULTS: RBM-Ti implants showed higher resorption of the remaining cortical bone
      and bone formation (rBA = 36.9% and nBA = 38.8%) than M-Y-TZP implants (rBA = 48%
      and nBA = 26.5%). The BIC values showed no differences among the groups in the
      cortical region (mean = 52.2%) but in the medullary region, they were 0.45-fold
      higher in the RBM-Ti group (51.2%) than in the M-Y-TZP group (35.2%). In all
      groups, high incorporation of tetracycline was observed (2nd to 4th weeks),
      followed by alizarin (4th to 6th weeks) and calcein (6th to 8th weeks). In the
      cortical region, incorporation of tetracycline was similar between RBM-Ti (49.8%)
      and M-Y-TZP (35.9%) implants, but higher than M-Ti (28.2%) implants.
      Subsequently, alizarin and calcein were 1.1-fold higher in RBM-Ti implants than
      in the other implants. In the medullary region, no significant differences were
      observed for all fluorochromes. CONCLUSION: All implants favored bone formation
      and consequently promoted primary stability. Bone formation around the threads
      was faster in RBM-Ti and M-Y-TZP implants than in M-Ti implants, but limited bone
      remodeling with M-Y-TZP implants over time can have significant effects on
      secondary stability, suggesting caution for its use as an alternative substitute
      for titanium implants.

PMID- 29044524
TI  - Effects of loss of occlusal contact on the expression of matrix metalloproteinase
      2, membrane type 1-MMP, tissue inhibitor of the MMP-2, eruption rate,
      organization and resistance of collagen fibers of the rat incisor periodontal
      ligament.
AB  - BACKGROUND AND OBJECTIVE: This study investigated the effect of occlusal contact
      loss (induced by tooth shortening), on matrix metalloproteinase (MMP)-2, membrane
      type 1-MMP (MT1-MMP) and tissue inhibitor of the MMP-2 (TIMP-2) expressions in
      the periodontal ligament of the rat incisor, as well as eruption rate, resistance
      and collagen organization. MATERIAL AND METHODS: Male Wistar rats were
      distributed into a control group, denominated normofunctional group, whose lower
      teeth underwent a normal eruption process; and a hypofunctional group, whose
      lower left incisor teeth were shortened every 2 days during 14 days. Parameters
      were evaluated on the first, seventh and 14th days and the eruption rate was
      determined according to the size of the incisor during the eruption process. MMP
      2 activity was determined by zymography and the expressions of the MT1-MMP and
      TIMP-2 proteins were quantitated by western blot. Collagen protein organization,
      as indicated by the birefringence of the periodontal ligament, was analyzed under
      polarized light and the periodontal ligament's resistance was determined from the
      load necessary to inject the incisor into its alveolar space, before extraction.
      RESULTS: Loss of occlusal contact, in rats submitted to hypofunctional eruption,
      increased MMP-2 activity and eruption rate, but decreased MT1-MMP and TIMP-2
      expression and disrupted collagen organization in the periodontal ligament,
      consequently reducing periodontal ligament resistance. CONCLUSION: We conclude
      that, after incisor eruption, occlusal contact may be an important factor for
      regulating the remodeling and the physiological resistance of the periodontal
      ligament against the continuous eruption process observed in rat incisors.

PMID- 29044526
TI  - An Investigation into the Relationship between Human Cranial and Pelvic Sexual
      Dimorphism.
AB  - When faced with commingled remains, it might be assumed that a more "masculine"
      pelvis is associated with a more "masculine" cranium, but this relationship has
      not been specifically tested. This study uses geometric morphometric analyses of
      pelvic and cranial landmarks to assess whether there is an intra-individual
      relationship between the degrees of sexual expression in these two skeletal
      regions. Principal component and discriminant function scores were used to assess
      sexual dimorphism in 113 U.S. Black individuals. Correlation values and partial
      least squares regression (PLS) were used to evaluate intra-individual
      relationships. Results indicate that the os coxae is more sexually dimorphic than
      the cranium, with element shape being more sexually dimorphic than size. PLS and
      correlation results suggest no significant intra-individual relationship between
      pelvic and cranial sexual size or shape expression. Thus, in commingled
      situations, associations between these skeletal elements cannot be inferred based
      on degree of "masculinity."

PMID- 29044525
TI  - Susceptibility of different mouse strains to peri-implantitis.
AB  - BACKGROUND AND OBJECTIVE: Peri-implantitis (PI) is an inflammatory condition that
      affects the tissues surrounding dental implants. Although the pathogenesis of PI
      is not fully understood, evidence suggests that the etiology is multifactorial
      and may include a genetic component. The aim of this study was to investigate the
      role of genetics in the development of peri-implantitis. MATERIAL AND METHODS:
      Four-week-old C57BL/6J, C3H/HeJ and A/J male mice had their left maxillary molars
      extracted. Implants were placed in the healed extraction sockets. Upon
      osseointegration, ligatures were placed around the implant head for 1 or 4 weeks
      to induce PI. Micro-computed tomography scanning was used to measure volumetric
      bone loss. Histological analyses were also performed to evaluate collagen
      organization and the presence of neutrophils and osteoclasts. RESULTS:
      Radiographically, comparing the ligature-treated mice, C57BL/6J displayed the
      greatest amount of bone loss, followed by C3H/HeJ and A/J mice at 1 and 4 weeks.
      Histologically, at 1 week, C57BL/6J mice presented with the highest numbers of
      neutrophils and osteoclasts. At 4 weeks, C57BL/6J mice presented with the most
      active bone remodeling compared with the other two strains. CONCLUSION: There
      were significant differences in the severity of peri-implantitis among the
      different mouse strains, suggesting that the genetic framework can affect implant
      survival and success. Future work is needed to dissect the genetic contribution
      to the development of peri-implantitis.

PMID- 29044527
TI  - Effect of the combined use of enamel matrix derivative and atelocollagen sponge
      scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells
      in vitro.
AB  - BACKGROUND AND OBJECTIVE: Induced pluripotent stem cells (iPSCs) are a candidate
      cell source in periodontal regenerative therapy. Enamel matrix derivative (EMD)
      has been shown to regenerate periodontal tissues, and atelocollagen sponge (ACS)
      is considered a suitable scaffold or carrier for growth factors. This study aimed
      to investigate the effect of combined use of EMD and an ACS scaffold on cell
      behaviors and differentiation of mouse iPSCs (miPSCs) in vitro. MATERIAL AND
      METHODS: Following embryonic body formation from miPSCs, dissociated cells (miPS
      EB-derived cells) were seeded onto ACS with or without EMD, and cultured in
      osteoblast differentiation medium. Scanning electron microscopy and histological
      analyses were used to assess cell morphology and infiltration within the ACS.
      Cell viability (metabolism) was determined using an MTS assay, and expression of
      mRNA of osteoblastic differentiation markers was assessed by quantitative RT 
      PCR. Alkaline phosphatase (ALP) staining intensity and activity were evaluated.
      Mineralization was assessed by von Kossa staining, and calcium content was
      quantitated using the methylxylenol blue method. RESULTS: By 24 hours after
      seeding, miPS-EB-derived cells in both the EMD and control groups had attached to
      and infiltrated the ACS scaffold. Scanning electron microscopy images revealed
      that by day 14, many cytoplasmic protrusions and extracellular deposits,
      suggestive of calcified matrix, were present in the EMD group. There was a time
      dependent increase in cell viability up to day 3, but no difference between
      groups was observed at any time point. The levels expressed of ALP and osterix
      genes were significantly higher in the EMD group than in the control group.
      Expression of runt-related transcription factor 2 was increased in the EMD group
      compared with the control group on day 7. EMD upregulated the expression of bone
      sialoprotein and osteopontin on day 14, whereas expression of osteocalcin was
      lower at all time points. The staining intensity and activity of ALP were higher
      in the EMD group than in the control group. Mineralization levels and calcium
      contents were significantly higher in the EMD group throughout the observation
      period. CONCLUSION: These data suggest that combining ACS with EMD increases
      levels of osteoblastic differentiation and mineralization in miPS-EB-derived
      cells, compared with ACS used alone.

PMID- 29044529
TI  - Automated identification of normoblast cell from human peripheral blood smear
      images.
AB  - In this paper, we have presented a new computer-aided technique for automatic
      detection of nucleated red blood cells (NRBCs) or normoblast cell from peripheral
      blood smear image. The proposed methodology initiates with the localization of
      the nucleated cells by adopting multilevel thresholding approach in smear images.
      A novel colour space transformation technique has been introduced to
      differentiate nucleated blood cells [white blood cells (WBCs) and NRBC] from red
      blood cells (RBCs) by enhancing the contrast between them. Subsequently, special
      fuzzy c-means (SFCM) clustering algorithm is applied on enhanced image to segment
      out the nucleated cell. Finally, nucleated RBC and WBC are discriminated by the
      random forest tree classifier based on first-order statistical-based features.
      Experimentally, we observed that the proposed technique achieved 99.42% accuracy
      in automatic detection of NRBC from blood smear images. Further, the technique
      could be used to assist the clinicians to diagnose a different anaemic condition.

PMID- 29044528
TI  - Endomorphins potentiate acid-sensing ion channel currents and enhance the lactic
      acid-mediated increase in arterial blood pressure: effects amplified in hindlimb
      ischaemia.
AB  - KEY POINTS: Chronic limb ischaemia, characterized by inflammatory mediator
      release and a low extracellular pH, leads to acid-sensing ion channel (ASIC)
      activation and reflexively increases mean arterial pressure; endomorphin release
      is also increased under inflammatory conditions. We examined the modulation of
      ASIC currents by endomorphins in sensory neurons from rats with freely perfused
      and ligated femoral arteries: peripheral artery disease (PAD) model. Endomorphins
      potentiated sustained ASIC currents in both groups of dorsal root ganglion
      neurons, independent of mu opioid receptor stimulation or G protein activation.
      Intra-arterial administration of lactic acid (to simulate exercising muscle and
      evoke a pressor reflex), endomorphin-2 and naloxone resulted in a significantly
      greater pressor response than lactic acid alone, while administration of APETx2
      inhibited endomorphin's enhancing effect in both groups. These results suggest a
      novel role for endomorphins in modulating ASIC function to effect lactic acid
      mediated reflex increase in arterial pressure in patients with PAD. ABSTRACT:
      Chronic muscle ischaemia leads to accumulation of lactic acid and other
      inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing
      ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in
      pH and evoke a pressor reflex known to increase mean arterial pressure. The
      naturally occurring endomorphins are also released by primary afferents under
      ischaemic conditions. We examined whether high affinity mu opioid receptor (MOR)
      agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic
      acid-mediated pressor reflex. In rat dorsal root ganglion (DRG) neurons, exposure
      to E-2 in acidic solutions significantly potentiated ASIC currents when compared
      to acidic solutions alone. The potentiation was significantly greater in DRG
      neurons isolated from rats whose femoral arteries were ligated for 72 h.
      Sustained ASIC current potentiation was also observed in neurons pretreated with
      pertussis toxin, an uncoupler of G proteins and MOR. The endomorphin-mediated
      potentiation was a result of a leftward shift of the activation curve to higher
      pH values and a slight shift of the inactivation curve to lower pH values. Intra
      arterial co-administration of lactic acid and E-2 led to a significantly greater
      pressor reflex than lactic acid alone in the presence of naloxone. Finally, E-2
      effects were inhibited by pretreatment with the ASIC3 blocker APETx2 and enhanced
      by pretreatment with the ASIC1a blocker psalmotoxin-1. These findings have
      uncovered a novel role of endomorphins by which the opioids can enhance the
      lactic acid-mediated reflex increase in arterial pressure that is MOR stimulation
      independent and APETx2-sensitive.

PMID- 29044530
TI  - Gingival tissue, an extrasynovial source of malondialdehyde-acetaldehyde adducts,
      citrullinated and carbamylated proteins.
AB  - BACKGROUND AND OBJECTIVE: Postranslational modification of proteins can lead to
      the production of autoantibodies and loss of immune tolerance. This process has
      been hypothesised to be a critical factor in the pathogenesis of rheumatoid
      arthritis. The objective of this study was to demonstrate that inflamed human
      gingival tissue provides an extrasynovial source of malondialdehyde-acetaldehyde
      adducts, citrullinated and carbamylated proteins all of which are considered to
      be linked to the development of rheumatoid arthritis. Identification of such
      modified proteins in inflamed gingiva may explain, in part, how inflammation of
      the periodontal tissues may influence the development of rheumatoid arthritis.
      MATERIAL AND METHODS: Gingival biopsies of healthy, mild and moderate
      periodontitis were triple stained with antibodies against malondialdehyde
      acetaldehyde adducts, citrullinated and carbamylated proteins. RESULTS:
      Assessment of healthy gingival tissue revealed negligible staining for
      carbamylated, malondialdehyde-acetaldehyde (MAA), or citrullinated proteins. Mild
      periodontitis was positive for all three modifications. Furthermore, there was an
      increase in staining intensity for carbamylated, citrullinated and MAA-modified
      proteins in moderate periodontitis. Negative staining results were observed for
      the isotype controls. CONCLUSION: This study provides evidence for the presence
      of citrullinated, carbamylated and MAA adduct modified proteins in inflamed
      periodontal tissues. The potential for these proteins to play a role in
      autoimmunity in a multi-system inflammatory syndromic disease model now needs to
      be determined.

PMID- 29044531
TI  - Mesenchymal chondrosarcoma: A Japanese Musculoskeletal Oncology Group (JMOG)
      study on 57 patients.
AB  - BACKGROUND: This study aimed to elucidate the clinical features and prognostic
      factors of mesenchymal chondrosarcoma (MCS) and investigate optimal treatment
      strategies. METHODS: Data from 57 patients with MCS were collected from a
      Japanese Musculoskeletal Oncology Group (JMOG) and retrospectively analyzed.
      RESULTS: Data from 29 males and 28 females were collected. Primary tumor sites
      were the head and neck (7 patients), trunk (35 patients), and extremities (15
      patients). The tumors originating in the trunk were significantly associated with
      a worse OS compared with those originating at the other sites in all patients and
      those with localized disease (P = 0.020 and P = 0.019, respectively). In patients
      with localized disease, the tumors originating in the head and neck were
      significantly associated with better OS and MFS compared with those originating
      in the trunk (P = 0.024 and P = 0.014, respectively). Positive surgical margin
      was significantly correlated with the worse LRFS (P = 0.018). Adjuvant
      chemotherapy exhibited a clear trend toward improved OS when MCS was localized in
      the trunk or extremities (P = 0.057). CONCLUSIONS: Adequate surgery is considered
      to be the mainstay of treatment for localized MCS. Prognosis was different
      depending on the site of tumor origin.

PMID- 29044532
TI  - Pancreaticojejunostomy: Does the technique matter? A randomized trial.
AB  - BACKGROUND: Despite a large number of studies, the ideal technique of
      pancreaticojejunostomy (PJ) after pancreaticoduodenectomy (PD) remains debatable.
      We compared the two most common techniques of PJ (duct-to-mucosa and dunking) in
      a randomized trial. METHODS: This open-label randomized trial was done at a
      tertiary care center from January 2009 to October 2015. Patients with resectable
      periampullary tumours with a pancreatic duct diameter >=2 mm, requiring PD were
      randomly assigned to one of the two techniques using computer generated random
      numbers. The primary outcome was postoperative pancreatic fistula (POPF) rate and
      secondary outcomes were frequency of other postoperative complications. RESULTS:
      A total of 193 patients were randomized and analyzed (intention-to-treat
      analysis), 97 in duct-to-mucosa and 96 in dunking group. Both groups were
      comparable for baseline demographic and clinical profiles. The incidence of POPF
      in the entire study group was 23.8%. There was no statistically significant
      difference between the two groups (24.7% vs 22.9%, P = 0.71). Similarly, the
      incidence of grades B and C (clinically significant) POPF was comparable (16.5%
      vs 13.5%, P = 0.57). Both groups were comparable with respect to the secondary
      outcomes. DISCUSSION: The duct-to-mucosa technique of PJ after PD is not superior
      to the dunking technique with respect to POPF rate. (CTRI/2010/091/000531).

PMID- 29044533
TI  - Effect of nephrectomy for retroperitoneal sarcoma on post-operative renal
      function.
AB  - BACKGROUND AND OBJECTIVES: Surgical resection of retroperitoneal sarcomas (RPS)
      often involves removal of the ipsilateral kidney. We evaluated the long-term post
      operative renal function in patients who underwent a nephrectomy as part of their
      en-bloc resection of RPS. METHODS: Retrospective review of an institutional
      database identified RPS patients who underwent nephrectomy for curative intent
      from 1990 to 2014. The primary outcome measured was chronic kidney disease (CKD)
      calculated by the glomerular filtration rate (GFR). RESULTS: Of the 47 patients
      in our study, 19 (40%), 18 (38%), and 10 (21%) patients had a preoperative CKD
      stage 1, 2, and 3, respectively. The GFR decreased by an average of 33.4
      mL/min/1.73 m2 with 66% of patients demonstrating mild progression of their renal
      impairment. Only three (6%) patients progressed to CKD stage 4 or 5, one of which
      required life-long dialysis. CONCLUSION: Nephrectomy as part of an en-bloc
      resection is associated with a decrease in GFR that is not clinically
      significant. Fear of kidney failure should not prevent a surgeon from performing
      a nephrectomy in the treatment of RPS.

PMID- 29044534
TI  - Effectors involved in fungal-fungal interaction lead to a rare phenomenon of
      hyperbiotrophy in the tritrophic system biocontrol agent-powdery mildew-plant.
AB  - Tritrophic interactions involving a biocontrol agent, a pathogen and a plant have
      been analyzed predominantly from the perspective of the biocontrol agent. We have
      conducted the first comprehensive transcriptomic analysis of all three organisms
      in an effort to understand the elusive properties of Pseudozyma flocculosa in the
      context of its biocontrol activity against Blumeria graminis f.sp. hordei as it
      parasitizes Hordeum vulgare. After inoculation of P. flocculosa, the tripartite
      interaction was monitored over time and samples collected for scanning electron
      microscopy and RNA sequencing. Based on our observations, P. flocculosa
      indirectly parasitizes barley, albeit transiently, by diverting nutrients
      extracted by B. graminis from barley leaves through a process involving unique
      effectors. This brings novel evidence that such molecules can also influence
      fungal-fungal interactions. Their release is synchronized with a higher
      expression of powdery mildew haustorial effectors, a sharp decline in the
      photosynthetic machinery of barley and a developmental peak in P. flocculosa. The
      interaction culminates with a collapse of B. graminis haustoria, thereby stopping
      P. flocculosa growth, as barley plants show higher metabolic activity. To
      conclude, our study has uncovered a complex and intricate phenomenon, described
      here as hyperbiotrophy, only achievable through the conjugated action of the
      three protagonists.

PMID- 29044535
TI  - Incidence and histologic features of mixed renal tumors.
AB  - BACKGROUND AND OBJECTIVES: Guidelines for management of renal cell carcinoma
      (RCC) incompletely address the implications of mixed renal tumor histology. We
      investigate the incidence of mixed renal tumors identified at renal surgery and
      determine the association with pathologic features. METHODS: Institutional kidney
      tumor database was reviewed to identify 536 patients who underwent partial or
      radical nephrectomy. Clinical, demographic, and pathologic data were collected. A
      linear fixed effects model and logistic regression determined the association of
      mixed tumor histology with tumor size, stage, grade, and nephrometry score.
      RESULTS: Three hundred and eighteen men and 218 women with a median BMI of 31 and
      median tumor size of 3.5 cm were included. 469 (87.5%) patients had pathologic
      kidney cancer with the most common histologies being clear cell carcinoma in 343
      (73.1%) patients, papillary in 81 (17.3%) patients, and chromophobe in 25 (5.3%)
      patients. Twenty (4.3%) patients had mixed tumors on final pathology. Clear cell
      RCC was the most common primary pathology in patients with mixed tumor histology
      (n = 14, 75%) with additional primary tumor histologies included papillary and
      chromophobe. When considering secondary histologies, 85% were coexistent primary
      renal cancers while 15% (n = 3) were benign renal tumors. No association of mixed
      tumor histology and adverse pathologic features was noted. CONCLUSIONS: Mixed
      tumor histology is an uncommon entity that is not associated with adverse
      features in a solitary renal mass. These results are especially relevant in
      discussing the role of renal mass biopsy, and provide further evidence that renal
      sampling is a valuable tool in the appropriate clinical context.

PMID- 29044536
TI  - Effect of matrix metalloproteinase inhibitor on disrupted E-cadherin after acid
      exposure in the human nasal epithelium.
AB  - OBJECTIVE: Laryngopharyngeal reflux disease (LPRD) is one of potential factors in
      recalcitrant chronic rhinosinusitis with or without polyps. An increase in
      junctional permeability in the nasal mucosa in LPRD may be due to disrupted
      protein bridge formation with cell-to-cell adhesion molecules such as E-cadherin.
      Despite the relationship between nasal mucosal inflammation and LPRD, the clear
      mechanism by which acid reflux affects the nasal epithelium remains unclear.
      METHODS: The expression levels and distribution patterns of E-cadherin in primary
      culture of nasal epithelial cells after acid exposure with or without
      dexamethasone and matrix metalloproteinase (MMP) inhibitor were determined using
      Western blot and immunocytochemistry. The functional roles of MMP inhibitor in
      maintaining junctional permeability in the nasal epithelium were elucidated by
      transepithelial permeability test. RESULTS: By acid exposure to nasal epithelial
      cells, mature E-cadherin was decreased and cleaved E-cadherin was increased. This
      was thought to be caused by cleavage of mature E-cadherin between cells and was
      confirmed by the increment of E-cadherin inside a cell in immunocytochemical
      evaluation. Whereas disruption of E-cadherin was not recovered by steroid
      medication with various treatments of dexamethasone, disrupted E-cadherin was
      restored to normal by inhibition of MMPs with actinonin, a broad MMP inhibitor.
      This recovery was functionally demonstrated by transepithelial permeability test.
      CONCLUSION: Our results suggest that altered expression of E-cadherin in the
      nasal epithelium by acid exposure may be a possible mechanism for nasal tissue
      injury in chronic nasal inflammation with LPRD, and that MMP inhibition is a
      potential treatment. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E1-E7, 2018.

PMID- 29044537
TI  - In vivo imaging of the internal nasal valve during different conditions using
      optical coherence tomography.
AB  - OBJECTIVE: Previously, we proposed long-range optical coherence tomography (LR
      OCT) to be an effective method for the quantitative evaluation of the nasal valve
      geometry. Here, the objective was to quantify the reduction in the internal nasal
      valve angle and cross-sectional area that results in subjective nasal airway
      obstruction and to evaluate the dynamic behavior of the valve during respiration
      using LR-OCT. METHODS: For 16 healthy individuals, LR-OCT was performed in each
      naris during: 1) normal respiration, 2) peak forced inspiration, 3) lateral nasal
      wall depression (to the onset of obstructive symptoms), and 4) after application
      of a topical decongestant. The angle and the cross-sectional area of the valve
      were measured. RESULTS: A reduction of the valve angle from 18.3 degrees  to 14.1
      degrees  (11 degrees  in Caucasians and 17 degrees  in Asians) and a decrease of
      the cross-sectional area from 0.65 cm2 to 0.55 cm2 led to subjective nasal
      obstruction. Forceful breathing did not significantly change the internal nasal
      valve area in healthy individuals. Application of nasal decongestant resulted in
      increased values. CONCLUSION: LR-OCT proved to be a fast and readily performed
      method for the evaluation of the dynamic behavior of the nasal valve. The values
      of the angle and the cross-sectional area of the valve were reproducible, and
      changes in size could be accurately delineated. LEVEL OF EVIDENCE: 2b.
      Laryngoscope, 128:E105-E110, 2018.

PMID- 29044538
TI  - Laparoscopic versus open surgery for rectal cancer after neoadjuvant
      chemoradiation: Long-term outcomes of a propensity score matched study.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic resection for rectal cancer has short
      term benefits when compared to open resection. The aim of this study was to
      compare the long-term oncological outcomes of laparoscopic and open resection for
      rectal cancer following neoadjuvant chemoradiation (NCRT). METHODS: In this
      propensity matched study, a series of 72 patients who underwent laparoscopic
      surgery for rectal cancer following NCRT between 2004 and 2010 (Lap group) were
      matched with 72 patients who underwent open surgery for rectal cancer in the same
      period (Open group). The survival and recurrence patterns were compared between
      the two groups. RESULTS: After a median follow-up of 69.5 months (range 1-138
      months), local recurrence rate was observed in 4 patients (5.5%) and 7 patients
      (9.7%) in the Lap and Open groups, respectively (P = 0.35). The 5- and 10-year
      disease-free survival in the Lap and Open groups were 61.3% versus 47.9% and
      48.8% versus 41%, respectively (P = 0.16). The 5- and 10-year overall survival
      was 66.9% versus 60.2% and 49% versus 46.2% in the Lap and Open groups,
      respectively (P = 0.38). CONCLUSION: Laparoscopic surgery following NCRT for low
      and mid third rectal cancers was associated with similar long-term oncological
      outcomes when compared to open surgery.

PMID- 29044539
TI  - Cervicofacial-facial artery myocutaneous flap (C-FAM flap): A novel flap in oral
      cavity reconstruction.
AB  - BACKGROUND: Reconstruction is an integral part of the surgical management of oral
      cancer. Local flaps are one of the options in reconstruction of small to moderate
      sized defects of oral cavity. Reconstruction is an integral part of the surgical
      management of oral cancer. Every defect needs to be assessed individually to
      tailor made the reconstruction because of its multidimensionality and complexity.
      Varieties of autologous tissues are being used in reconstruction like local,
      regional, or free flaps which can be simple or complex tissues. There is always a
      trend to identify the newer flaps/technique to personalize reconstruction. Local
      flaps are also one of the options in reconstruction of small to moderate sized
      defects of oral cavity. Local tissue if it is available is in the primary
      surgeon's purview and the flap can be raised without much technical difficulty
      and morbidity. We used perforator based tissue from the face and neck which is
      richly supplied by the facial vessels and named as the Cervicofacial- Facial
      Artery Myocutaneous flap (C-FAM flap) for reconstruction of oral cavity. METHODS:
      We used perforator based local tissue from the face and neck which is supplied by
      facial vessels and named it as the C-FAM flap for the reconstruction of oral
      cavity defects. RESULTS: Twenty-eight patients underwent C-FAM flap
      reconstruction in different subsites of the oral cavity with acceptable
      functional rehabilitation. There was no flap loss. CONCLUSION: The C-FAM flap is
      a robust flap, which is reliable, pliable, and rich in its vascularity. It has to
      be one of the armamentarium for the oral cavity reconstruction. C-FAM flap: A
      Novel flap in Oral cavity reconstruction.

PMID- 29044540
TI  - Factors affecting hospital length of stay following pelvic exenteration surgery.
AB  - BACKGROUND AND OBJECTIVES: Total pelvic exenteration are performed in patients
      with locally advanced or recurrent pelvic malignances. Many patients have prolong
      hospital length of stay (LOS), but risk factors are not clearly identified.
      METHODS: From 2002 through 2012, 100 consecutive patients undergoing pelvic
      exenteration were retrospectively reviewed. A general linear model was used to
      examine risk factors for prolonged hospital LOS. RESULTS: Among the 100 patients,
      51 had gastrointestinal cancer, 14 had genitourinary cancer, 31 had gynecologic
      cancer, and 4 had sarcoma. Perioperative complications included infection (n =
      44), anastomotic leak/fistula (n = 6), wound or flap dehiscence (n = 11), and
      ileus or bowel obstruction (n = 30). The median (Interquartile range (IQR))
      hospital LOS was 15 days (10-21.5 days). On multivariate regression analysis,
      hospital LOS was significantly prolonged by underweight status, genitourinary
      cancer or sarcoma diagnosis, >=2 infections, anastomotic leak/fistula, requiring
      rehabilitation consult and admission, and >=2 consultations (P = 0.05).
      CONCLUSION: In patients undergoing pelvic exenteration, prolonged hospital LOS is
      associated with underweight status, genitourinary cancer or sarcoma diagnosis,
      more than one infection, anastomotic leak/fistula, requiring rehabilitation
      consult and admission, and more than one consultation. Further study is needed to
      assess whether minimizing these risk factors can improve hospital LOS in these
      patients.

PMID- 29044541
TI  - Validation of Sendai and Fukuoka consensus guidelines in predicting malignancy in
      patients with preoperatively diagnosed mucinous pancreatic cystic neoplasms.
AB  - BACKGROUND AND OBJECTIVES: The Sendai consensus guidelines (SCG) and Fukuoka
      consensus guidelines (FCG) have been examined for their roles in predicting
      advanced neoplasia (AN) in pancreatic cystic neoplasm (PCN) patients with mixed
      results. We aim to evaluate the utilities of both guidelines in a Chinese cohort
      with preoperatively diagnosed mucinous PCNs. METHODS: One hundred ninety-seven
      patients who underwent resections from 2008 to 2015 in Zhong Shan Hospital, Fudan
      University for suspected PCNs were retrospectively reviewed. Receiver operating
      characteristic (ROC) curves were calculated and compared to measure diagnostic
      value. RESULTS: Fifty-five patients were diagnosed with AN pathologically. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of the SCG high-risk (SCGHR ) criteria were 87.3%, 28.2%, 32.0%,
      85.1%, and 44.7%, respectively, and for the FCG high-risk (FCGHR ) criteria, they
      were 40.0%, 95.8%, 78.6%, 80.5%, and 80.2%, respectively. ROC curve comparison
      analyses showed that the FCGHR were superior to the SCGHR (P = 0.02). The
      performance of the FCGHR was enhanced with CA19-9 incorporated (P = 0.004).
      CONCLUSIONS: The FCG were superior to the SCG in this retrospective analysis,
      which could be further improved by the incorporation of CA19-9. However, the
      practical safety remains uncertain because of missed invasive carcinoma cases.

PMID- 29044542
TI  - Survival outcome of women with stage IV uterine carcinosarcoma who received
      neoadjuvant chemotherapy followed by surgery.
AB  - BACKGROUND AND OBJECTIVES: To examine survival of women with stage IV uterine
      carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by
      hysterectomy. METHODS: This is a nested case-control study within a retrospective
      cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by
      hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who
      had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage
      IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival
      (CSS) were examined. RESULTS: The most common regimen for neoadjuvant
      chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant
      chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy
      group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95%
      confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable
      between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the
      types of neoadjuvant chemotherapy regimens were compared, women who received a
      carboplatin/paclitaxel regimen had better survival outcomes compared to those who
      received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and
      CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. CONCLUSION: Our study found
      that there is no statistically significant difference in survival between women
      with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who
      undergo primary surgery.

PMID- 29044543
TI  - Investigating the effects of laryngotracheal stenosis on upper airway
      aerodynamics.
AB  - OBJECTIVE: Very little is known about the impact of laryngotracheal stenosis
      (LTS) on inspiratory airflow and resistance, especially in air hunger states.
      This study investigates the effect of LTS on airway resistance and volumetric
      flow across three different inspiratory pressures. METHODS: Head-and-neck
      computed tomography scans of 11 subjects from 2010 to 2016 were collected. Three
      dimensional reconstructions of the upper airway from the nostrils to carina,
      including the oral cavity, were created for one subject with a normal airway and
      for 10 patients with LTS. Airflow simulations were conducted using computational
      fluid dynamics modeling at three different inspiratory pressures (10, 25, 40
      pascals [Pa]) for all subjects under two scenarios: 1) inspiration through
      nostrils only (MC), and 2) through both nostrils and mouth (MO). RESULTS:
      Volumetric flows in the normal subject at the three inspiratory pressures were
      considerably higher (MC: 11.8-26.1 L/min; MO: 17.2-36.9 L/min) compared to those
      in LTS (MC: 2.86-6.75 L/min; MO: 4.11-9.00 L/min). Airway resistances in the
      normal subject were 0.051 to 0.092 pascal seconds per milliliter (Pa.s)/mL (MC)
      and 0.035-0.065 Pa.s/mL (MO), which were approximately tenfold lower than those
      of subjects with LTS: 0.39 to 0.89 Pa.s/mL (MC) and 0.45 to 0.84 Pa.s/mL (MO).
      Furthermore, subjects with glottic stenosis had the greatest resistance, whereas
      subjects with subglottic stenosis had the greatest variability in resistance.
      Subjects with tracheal stenosis had the lowest resistance. CONCLUSION: This pilot
      study demonstrates that LTS increases resistance and decreases airflow. Mouth
      breathing significantly improved airflow and resistance but cannot completely
      compensate for the effects of stenosis. Furthermore, location of stenosis appears
      to modulate the effect of the stenosis on resistance differentially. LEVEL OF
      EVIDENCE: NA. Laryngoscope, 128:E141-E149, 2018.

PMID- 29044545
TI  - Predicted global warming scenarios impact on the mother plant to alter seed
      dormancy and germination behaviour in Arabidopsis.
AB  - Seed characteristics are key components of plant fitness that are influenced by
      temperature in their maternal environment, and temperature will change with
      global warming. To study the effect of such temperature changes, Arabidopsis
      thaliana plants were grown to produce seeds along a uniquely designed
      polyethylene tunnel having a thermal gradient reflecting local global warming
      predictions. Plants therefore experienced the same variations in temperature and
      light conditions but different mean temperatures. A range of seed-related plant
      fitness estimates were measured. There were dramatic non-linear temperature
      effects on the germination behaviour in two contrasting ecotypes. Maternal
      temperatures lower than 15-16  degrees C resulted in significantly greater
      primary dormancy. In addition, the impact of nitrate in the growing media on
      dormancy was shown only by seeds produced below 15-16  degrees C. However, there
      were no consistent effects on seed yield, number, or size. Effects on germination
      behaviour were shown to be a species characteristic responding to temperature and
      not time of year. Elevating temperature above this critical value during seed
      development has the potential to dramatically alter the timing of subsequent seed
      germination and the proportion entering the soil seed bank. This has potential
      consequences for the whole plant life cycle and species fitness.

PMID- 29044544
TI  - Primary systemic therapy in resectable pancreatic ductal adenocarcinoma using
      mFOLFIRINOX: A pilot study.
AB  - BACKGROUND AND OBJECTIVES: Surgery followed by gemcitabine and/or a
      fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX
      (oxaliplatin 85 mg/m2 , irinotecan 180 mg/m2 , leucovorin 400 mg/m2 Day 1, 5-FU
      2400 mg/m2  * 48 h IV, peg-filgrastim 6 mg SQ day 3, every 14 days) has
      substantial activity in metastatic PDAC. We wished to determine the
      tolerability/efficacy of peri-operative mFOLFIRINOX in resectable PDAC. METHODS:
      Patients with resectable PDAC (ECOG PS 0/1) received four cycles of mFOLFIRINOX
      pre- and post-surgery. The primary endpoint was completion of preoperative
      chemotherapy plus resection. Secondary endpoints included completion of all
      therapy, R0 resection, treatment related toxicity, PFS, and OS. RESULTS: Twenty
      one patients enrolled: median age 62 (47-78); 20/21 (95%) completed four cycles
      of preoperative mFOLFIRINOX; response by RECIST was 1 CR, 3 PR, 16 SD; 17/21
      (81%) completed resection, 16/21 (76%) R0; 14/21 (66%) completed four cycles of
      postoperative mFOLFIRINOX. Grade 3 and 4 toxicity occurred in 23% and 14%
      patients pre-operatively, 26% and 6.0% post-operatively. Nine patients are alive
      with median follow-up of 27.7 (3.1-47.1) months. CONCLUSIONS: PST using
      mFOLFIRINOX in resectable PDAC is feasible and tolerable. R0 resection rate is
      high and survival promising, requiring longer follow-up and larger studies for
      definitive assessment.

PMID- 29044546
TI  - Associations Between Depression/Anxiety and Headache Frequency in Migraineurs: A
      Cross-Sectional Study.
AB  - BACKGROUND: While migraines have been associated with emotional disturbances, it
      remains unknown whether the intensity of emotional expression is directly related
      to migraine frequency. OBJECTIVE: The present study investigated
      depression/anxiety among migraineurs. METHODS: This cross-sectional study
      included 588 clinical outpatients in Taiwan. Migraines were stratified by attack
      frequency, with and without auras, and with well-controlled confounding
      variables. Demographic and clinical data, including sleep characteristics, were
      collected. Multivariable linear regressions were employed to examine whether
      migraine frequency (1-4 headache days per month, 5-8 headache days per month, 9
      14 headache days per month, or >14 headache days per month) was associated with
      depression/anxiety symptoms, as indicated by the Beck's Depression Inventory
      (BDI) and Hospital Anxiety and Depression Subscales (HADS). RESULTS: BDI total
      scores were highest in patients with chronic migraines (mean +/- SD: 13.2 +/-
      8.5), followed by those with high frequency (12.1 +/- 8.5), medium frequency
      (10.6 +/- 8.0), low frequency (9.1 +/- 7.1), and lowest in nonmigraine controls
      (6.6 +/- 5.9), with a significant trend in frequency (P trend < .001); similar
      results were obtained for HADS scores. BDI and HADS scores were independently
      related to high-frequency episodic and chronic migraine frequency and to poor
      sleep quality. The relationship between BDI score and migraine frequency was
      present in both aura-present (P trend = .001) and aura-absent subgroups (P trend
      = .029). CONCLUSION: Higher migraine frequency, either with or without auras,
      correlated with higher symptom scores of anxiety and depression.

PMID- 29044547
TI  - Effects of Early Dual-Eligible Special Needs Plans on Health Expenditure.
AB  - OBJECTIVE: To examine the effects of the penetration of dual-eligible special
      needs plans (D-SNPs) on health care spending. DATA SOURCES/STUDY SETTING:
      Secondary state-level panel data from Medicare-Medicaid Linked Enrollee Analytic
      Data Source (MMLEADS) public use file and Special Needs Plan Comprehensive
      Reports, Area Health Resource Files, and Medicaid Managed Care Enrollment Report
      between 2007 and 2011. STUDY DESIGN: A difference-in-difference strategy that
      adjusts for dual-eligibles' demographic and socioeconomic characteristics, state
      health resources, beneficiaries' health risk factors, Medicare/Medicaid
      enrollment, and state- and year-fixed effects. DATA COLLECTION/EXTRACTION
      METHODS: Data from MMLEADS were summarized from Centers for Medicare and Medicaid
      Services (CMS)'s Chronic Conditions Data Warehouse, which contains 100 percent of
      Medicare enrollment data, claims for beneficiaries who are enrolled in the fee
      for-service (FFS) program, and Medicaid Analytic Extract files. The MMLEADS
      public use file also includes payment information for managed care. Data in
      Special Needs Plan Comprehensive Reports were from CMS's Health Plan Management
      System. PRINCIPAL FINDINGS: Results indicate that D-SNPs penetration was
      associated with reduced Medicare spending per dual-eligible beneficiary.
      Specifically, a 1 percent increase in D-SNPs penetration was associated with 0.2
      percent reduction in Medicare spending per beneficiary. We found no association
      between D-SNPs penetration and Medicaid or total spending. CONCLUSION: Involving
      Medicaid services in D-SNPs may be crucial to improve coordination between
      Medicare and Medicaid programs and control Medicaid spending among dual-eligible
      beneficiaries. Starting from 2013, D-SNPs were mandated to have contracts with
      state Medicaid agencies. This change may introduce new effects of D-SNPs on
      health care spending. More research is needed to examine the impact of D-SNPs on
      dual-eligible spending.

PMID- 29044548
TI  - BRCA mutations in women with inflammatory breast cancer.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) often affects women at a relatively
      young age. To the authors' knowledge, the rate of BRCA variants among patients
      with IBC is not known. To determine the association between BRCA status and IBC,
      the authors evaluated its rate and compared the clinicopathologic characteristics
      of patients with IBC with those of patients with other breast cancers (non-IBC).
      METHODS: Patients who presented at the study institution's cancer genetics
      program and who underwent BRCA genetic testing were included in the current
      study. The authors compared clinicopathologic data between patients with IBC and
      those with non-IBC using propensity score matching to identify predictors.
      RESULTS: A total of 1789 patients who underwent BRCA genetic testing (1684 with
      non-IBC and 105 with IBC) were included. BRCA pathogenic variants were found in
      27.3% of patients with non-IBC and 18.1% of patients with IBC (P = .0384). After
      propensity score matching, there were no significant differences noted between
      patients with IBC and those with non-IBC, including the rate of BRCA pathogenic
      variants (P = .5485). However, a subgroup analysis of the 479 patients with BRCA
      pathogenic variants demonstrated that patients with IBC (19 patients) were
      diagnosed at significantly younger ages compared with patients with non-IBC (P =
      .0244). CONCLUSIONS: There was no clear association observed between BRCA
      pathogenic variants and IBC. However, among patients who tested positive for BRCA
      pathogenic variants, those with IBC were younger at the time of diagnosis
      compared with those with non-IBC breast cancers. These results confirm that
      genetic testing is important for patients with IBC who meet the current clinical
      criteria for genetic testing in breast cancer. Cancer 2018;124:466-74. (c) 2017
      American Cancer Society.

PMID- 29044549
TI  - Effects of clioquinol on the scuticociliatosis-causing protozoan Miamiensis
      avidus in olive flounder Paralichthys olivaceus.
AB  - Scuticociliatosis is a devastating and intractable protozoal disease in olive
      flounder, leading to a significant loss throughout the year. This study aimed to
      investigate a systemically effective antiscuticociliatosis agent for olive
      flounder for better absorption into the infected internal organs. The in vitro
      and in vivo antiscuticociliatosis effects of clioquinol (CQ) were examined after
      screening 30 biocidal agents against the highly pathogenic scuticociliate
      Miamiensis avidus. CQ was the most potent in vitro drug of those tested against
      cultured M. avidus. CQ was the least toxic in healthy olive flounder among the
      drugs that exhibit high potencies. In olive flounder, a single intramuscular
      injection of 40 mg/kg CQ significantly reduced mortality caused by artificial
      infection with M. avidus, and 10-20 mg/kg CQ increased fish survival times. CQ
      was also effective in naturally infected scuticociliatosis. Ciliate cell numbers
      were lower when CQ was injected in most organs, including the brain. CQ was well
      absorbed by the internal organs after intramuscular injection. This study
      suggests that CQ can be considered as a potential antiscuticociliatosis agent for
      systemic administration in olive flounder.

PMID- 29044550
TI  - Proliferative diabetic retinopathy characterization based on fractal features:
      Evaluation on a publicly available dataset.
AB  - PURPOSE: Diabetic retinopathy (DR) is one of the most widespread causes of
      preventable blindness in the world. The most dangerous stage of this condition is
      proliferative DR (PDR), in which the risk of vision loss is high and treatments
      are less effective. Fractal features of the retinal vasculature have been
      previously explored as potential biomarkers of DR, yet the current literature is
      inconclusive with respect to their correlation with PDR. In this study, we
      experimentally assess their discrimination ability to recognize PDR cases.
      METHODS: A statistical analysis of the viability of using three reference fractal
      characterization schemes - namely box, information, and correlation dimensions -
      to identify patients with PDR is presented. These descriptors are also evaluated
      as input features for training l1 and l2 regularized logistic regression
      classifiers, to estimate their performance. RESULTS: Our results on MESSIDOR, a
      public dataset of 1200 fundus photographs, indicate that patients with PDR are
      more likely to exhibit a higher fractal dimension than healthy subjects or
      patients with mild levels of DR (P<=1.3*10-2). Moreover, a supervised classifier
      trained with both fractal measurements and red lesion-based features reports an
      area under the ROC curve of 0.93 for PDR screening and 0.96 for detecting
      patients with optic disc neovascularizations. CONCLUSIONS: The fractal dimension
      of the vasculature increases with the level of DR. Furthermore, PDR screening
      using multiscale fractal measurements is more feasible than using their derived
      fractal dimensions. Code and further resources are provided at
      https://github.com/ignaciorlando/fundus-fractal-analysis.

PMID- 29044552
TI  - Dynamics of cognitive control: Theoretical bases, paradigms, and a view for the
      future.
AB  - Cognitive control (with the closely related concepts of attention control and
      executive function) encompasses the collection of processes that are involved in
      generating and maintaining appropriate task goals and suppressing task goals that
      are no longer relevant, as well as the way in which current goal representations
      are used to modify attentional biases to improve task performance. Here, we
      provide a comprehensive but nonexhaustive review of this complex literature, with
      an emphasis on the contributions made by techniques for studying human brain
      function. The review is divided into five sections: (a) overview and historical
      perspective of cognitive control, its subcomponent processes, and its neural
      substrate; (b) most common types of tasks used to assess and/or manipulate the
      level of control; (c) main research findings obtained with various imaging
      methodologies, with a focus on ERP data, and briefer overviews of oscillatory
      (event-related spectral perturbations) and fMRI data; (d) major theories of
      cognitive control; and (e) discussion of open questions regarding how to
      integrate the various dimensions of control, as well as the faster versus slower
      temporal dynamics informing this complex and multifaceted concept.

PMID- 29044551
TI  - Disordered eating and obesity: associations between binge-eating disorder, night
      eating syndrome, and weight-related comorbidities.
AB  - Binge-eating disorder (BED) and night-eating syndrome (NES) are two forms of
      disordered eating associated with overweight and obesity. While these disorders
      also occur in nonobese persons, they seem to be associated with weight gain over
      time and higher risk of diabetes and other metabolic dysfunction. BED and NES are
      also associated with higher risk of psychopathology, including mood, anxiety, and
      sleep problems, than those of similar weight status without disordered eating.
      Treatments are available, including cognitive behavior therapy (CBT),
      interpersonal psychotherapy, lisdexamfetamine, and selective serotonin reuptake
      inhibitors (SSRIs) for BED; and CBT, SSRIs, progressive muscle relaxation, and
      bright light therapy for NES.

PMID- 29044553
TI  - Elevated ozone reduces photosynthetic carbon gain by accelerating leaf senescence
      of inbred and hybrid maize in a genotype-specific manner.
AB  - Exposure to elevated tropospheric ozone concentration ([O3 ]) accelerates leaf
      senescence in many C3 crops. However, the effects of elevated [O3 ] on C4 crops
      including maize (Zea mays L.) are poorly understood in terms of physiological
      mechanism and genetic variation in sensitivity. Using free air gas concentration
      enrichment, we investigated the photosynthetic response of 18 diverse maize
      inbred and hybrid lines to season-long exposure to elevated [O3 ] (~100 nl L-1 )
      in the field. Gas exchange was measured on the leaf subtending the ear throughout
      the grain filling period. On average over the lifetime of the leaf, elevated [O3
      ] led to reductions in photosynthetic CO2 assimilation of both inbred (-22%) and
      hybrid (-33%) genotypes. There was significant variation among both inbred and
      hybrid lines in the sensitivity of photosynthesis to elevated [O3 ], with some
      lines showing no change in photosynthesis at elevated [O3 ]. Based on analysis of
      inbred line B73, the reduced CO2 assimilation at elevated [O3 ] was associated
      with accelerated senescence decreasing photosynthetic capacity and not altered
      stomatal limitation. These findings across diverse maize genotypes could advance
      the development of more O3 tolerant maize and provide experimental data for
      parameterization and validation of studies modeling how O3 impacts crop
      performance.

PMID- 29044555
TI  - Openness to experience and adapting to change: Cardiovascular stress habituation
      to change in acute stress exposure.
AB  - Underlying psychophysiological mechanisms of effect linking openness to
      experience to health outcomes, and particularly cardiovascular well-being, are
      unknown. This study examined the role of openness in the context of
      cardiovascular responsivity to acute psychological stress. Continuous
      cardiovascular response data were collected for 74 healthy young female adults
      across an experimental protocol, including differing counterbalanced acute
      stressors. Openness was measured via self-report questionnaire. Analysis of
      covariance revealed openness was associated with systolic blood pressure (SBP; p
      = .016), and diastolic blood pressure (DBP; p = .036) responsivity across the
      protocol. Openness was also associated with heart rate (HR) responding to the
      initial stress exposure (p = .044). Examination of cardiovascular adaptation
      revealed that higher openness was associated with significant SBP (p = .001), DBP
      (p = .009), and HR (p = .002) habituation in response to the second differing
      acute stress exposure. Taken together, the findings suggest persons higher in
      openness are characterized by an adaptive cardiovascular stress response profile
      within the context of changing acute stress exposures. This study is also the
      first to demonstrate individual differences in cardiovascular adaptation across a
      protocol consisting of differing stress exposures. More broadly, this research
      also suggests that future research may benefit from conceptualizing an adaptive
      fitness of openness within the context of change. In summary, the present study
      provides evidence that higher openness stimulates short-term stress responsivity,
      while ensuring cardiovascular habituation to change in stress across time.

PMID- 29044554
TI  - Contact dermatitis caused by a new rubber compound detected in canvas shoes.
AB  - BACKGROUND: In 2015 and 2016, female patients in Flanders consulted a
      dermatologist because they developed skin lesions after wearing a specific brand
      of canvas shoes. OBJECTIVES: To identify the culprit allergen in the shoes.
      METHODS: Eighteen young females aged 14-22 years presented with itching and
      erythematous to purple-coloured eczematous lesions on both feet. They were patch
      tested by 10 dermatologists with the European baseline series. Some patients
      underwent testing with additional series. Pieces of the shoe fabrics were tested
      in 11 of 18 patients. Chemical analysis of the shoe materials was performed.
      Finally, patients were tested with a thin-layer chromatogram of the shoe extracts
      and dilutions of the suspected rubber compound. RESULTS: All 18 patients showed
      positive reactions to thiuram mix. Ten of 11 patients reacted to a piece of shoe
      fabric. Chemical analysis showed the presence of
      dimethylthiocarbamylbenzothiazole sulfide (DMTBS). No thiurams were detected.
      Four patients tested with the chromatogram developed positive reactions to DMTBS.
      Positive reactions to low concentrations were observed in the 4 patients tested
      with a DMTBS dilution series; one patient reacted to 0.00001% in acetone.
      CONCLUSIONS: DMTBS, the culprit allergen, is a component formed during rubber
      vulcanization that probably cross-reacts with the thiuram mix.

PMID- 29044556
TI  - The social play, social skills and parent-child relationships of children with
      ADHD 12 months following a RCT of a play-based intervention.
AB  - BACKGROUND/AIM: There is an urgent need to investigate the long-term impact of
      social skill interventions for children with attention deficit hyperactivity
      disorder (ADHD). Interventions targeting the social skills of children with ADHD
      have limited short-term effectiveness and rarely investigate the long-term
      impact. Furthermore, these interventions are most frequently conducted in the
      clinic setting, without including the child's natural settings and interactants,
      such as their regular playmates and parents. METHODS: The present study
      investigated the social play, social skills and parent-child relationships of
      children with ADHD and their playmates (n = 13/group) aged 5-13 years. A two
      group before and after design with a longitudinal component was applied.
      Participant data compared over two time points, immediately following a
      randomised, controlled trial (RCT) of a play-based intervention and 12 months
      post-RCT. RESULTS: From immediately following the RCT to the 12-month follow-up,
      children with ADHD maintained social play skill gains in the home environment.
      Playmates maintained social play skill gains across the home and clinic
      environments. Children scored within a developmentally appropriate range, falling
      within 1 standard deviation of the mean for social skills and most parent-child
      relationship scales using norm-based assessments. CONCLUSION: Results support the
      long-term effectiveness of the intervention.

PMID- 29044557
TI  - Rice phytoglobins regulate responses under low mineral nutrients and abiotic
      stresses in Arabidopsis thaliana.
AB  - Just like animals, plants also contain haemoglobins (known as phytoglobins in
      plants). Plant phytoglobins (Pgbs) have been categorized into 6 different
      classes, namely, Phytogb0 (Pgb0), Phytogb1 (Pgb1), Phytogb2 (Pgb2), SymPhytogb
      (sPgb), Leghaemoglobin (Lb), and Phytogb3 (Pgb3). Among the 6 Phytogbs, sPgb and
      Lb have been functionally characterized, whereas understanding of the roles of
      other Pgbs is still evolving. In our present study, we have explored the function
      of 2 rice Pgbs (OsPgb1.1 and OsPgb1.2). OsPgb1.1, OsPgb1.2, OsPgb1.3, and
      OsPgb1.4 displayed increased level of transcript upon salt, drought, cold, and
      ABA treatment. The overexpression (OX) lines of OsPgb1.2 in Arabidopsis showed a
      tolerant phenotype in terms of better root growth in low potassium (K+ )
      conditions. The expression of the known K+ gene markers such as LOX2, HAK5, and
      CAX3 was much higher in the OsPgb1.2 OX as compared to wild type. Furthermore,
      the OsPgb1.2 OX lines showed a decrease in reactive oxygen species (ROS)
      production and conversely an increase in the K+ content, both in root and shoot,
      as compared to wild type in K+ limiting condition. Our results indicated the
      potential involvement of OsPgb1.2 in signalling networks triggered by the
      nutrient deficiency stresses.

PMID- 29044558
TI  - Adolescent pregnancy and nutrition: a subgroup analysis from the Mamachiponde
      study in Malawi.
AB  - Young age at childbearing (<=19 years) is common and associated with poor birth
      outcomes. A trial among Malawian pregnant women with moderate malnutrition was
      used to determine outcomes of young adolescents (<=18 years), older adolescents
      (18-20 years), and adults (>20 years). Women received one of three supplementary
      foods that provided ~900 kcal/day and 33-36 g protein/day and returned every 2
      weeks. Newborn/maternal measurements were taken at delivery and after 6 and 12
      weeks. Upon enrollment, adolescents had greater body mass index than adults (19.9
      +/- 1.3 versus 19.5 +/- 1.4 kg/m2 , P < 0.001). Young adolescents received more
      rations of food and enrolled and delivered with a lower fundal height than adults
      (21.7 +/- 5.2 versus 23.0 +/- 5.6, P = 0.00 enrollment; 30.2 +/- 3.1 versus 31.0
      +/- 2.8, P < 0.001 delivery). Among newborns, length for age was lowest in young
      adolescents, greater in older adolescents, and greatest in adults (Z-scores -1.7
      +/- 1.2, -1.4 +/- 1.2, and -1.1 +/- 1.1, respectively; P < 0.001). These
      differences persisted in length for age at 6 and 12 weeks of age for infants.
      Adolescents enrolled earlier in pregnancy and appeared more nutritionally
      adequate than adults; adolescent outcomes were inferior to those of adults,
      suggesting that they were subject to more physiologic stressors and/or different
      nutritional needs.

PMID- 29044559
TI  - Discovery and characterization of novel trans-spliced products of human polyoma
      JC virus late transcripts from PML patients.
AB  - Although the human neurotropic polyomavirus, JC virus (JCV), was isolated almost
      a half century ago, understanding the molecular mechanisms governing its biology
      remains highly elusive. JCV infects oligodendrocytes and astrocytes in the
      central nervous system (CNS) and causes a rare fatal brain disease known as
      progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals
      including AIDS. It has a small circular DNA genome (~5 kb) and generates two
      primary transcripts from its early and late coding regions, producing several
      predicted alternatively spliced products mainly by cis-splicing. Here, we report
      the discovery and characterization of two novel open reading frames (ORF1 and
      ORF2) associated with JCV late transcripts, generated by an unusual splicing
      process called trans-splicing. These ORFs result from (i) the trans-splicing of
      two different lengths of the 5'-short coding region of VP1 between the coding
      regions of agnoprotein and VP2 after replacing the intron located between these
      two coding regions and (ii) frame-shifts occurring within the VP2 coding
      sequences terminated by a stop codon. ORF1 and ORF2 are capable of encoding 58
      and 72 aa long proteins respectively and are expressed in infected cells and PML
      patients. Each ORF protein shares a common coding region with VP1 and has a
      unique coding sequence of their own. When the expression of the unique coding
      regions of ORFs is blocked by a stop codon insertion in the viral background, the
      mutant virus replicates less efficiently when compared to wild-type, suggesting
      that the newly discovered ORFs play critical roles in the JCV life cycle.

PMID- 29044560
TI  - Regulating the transcriptomes that mediate the conversion of fibroblasts to
      various nervous system neural cell types.
AB  - Our understanding of the mechanism of cell fate transition during the direct
      reprogramming of fibroblasts into various central nervous system (CNS) neural
      cell types has been limited by the lack of a comprehensive analysis on generated
      cells, independently and in comparison with other CNS neural cell types. Here, we
      applied an integrative approach on 18 independent high throughput expression data
      sets to gain insight into the regulation of the transcriptome during the
      conversion of fibroblasts into induced neural stem cells, induced neurons (iNs),
      induced astrocytes, and induced oligodendrocyte progenitor cells (iOPCs). We
      found common down-regulated genes to be mostly related to fibroblast-specific
      functions, and suggest their potential as markers for screening of the silencing
      of the fibroblast-specific program. For example, Tagln was significantly down
      regulated across all considered data sets. In addition, we identified specific
      profiles of up-regulated genes for each CNS neural cell types, which could be
      potential markers for maturation and efficiency screenings. Furthermore, we
      identified the main TFs involved in the regulation of the gene expression program
      during direct reprogramming. For example, in the generation of iNs from
      fibroblasts, the Rest TF was the main regulator of this reprogramming. In
      summary, our computational approach for meta-analyzing independent expression
      data sets provides significant details regarding the molecular mechanisms
      underlying the regulation of the gene expression program, and also suggests
      potentially useful candidate genes for screening down-regulation of fibroblast
      gene expression profile, maturation, and efficiency, as well as candidate TFs for
      increasing the efficiency of the reprogramming process.

PMID- 29044561
TI  - Aquatic treadmill water level influence on pelvic limb kinematics in cranial
      cruciate ligament-deficient dogs with surgically stabilised stifles.
AB  - OBJECTIVE: To compare pelvic limb joint kinematics and temporal gait
      characteristics during land-based and aquatic-based treadmill walking in dogs
      that have undergone surgical stabilisation for cranial cruciate ligament
      deficiency. MATERIALS AND METHODS: Client-owned dogs with surgically stabilised
      stifles following cranial cruciate ligament deficiency performed three walking
      trials consisting of three consecutive gait cycles on an aquatic treadmill under
      four water levels. Hip, stifle and hock range of motion; peak extension; and peak
      flexion were assessed for the affected limb at each water level. Gait cycle time
      and stance phase percentage were also determined. RESULTS: Ten client-owned dogs
      of varying breeds were evaluated at a mean of 55.2 days postoperatively. Aquatic
      treadmill water level influenced pelvic limb kinematics and temporal gait
      outcomes. Increased stifle joint flexion was observed as treadmill water level
      increased, peaking when the water level was at the hip. Similarly, hip flexion
      increased at the hip water level. Stifle range of motion was greatest at stifle
      and hip water levels. Stance phase percentage was significantly decreased when
      water level was at the hip. CLINICAL SIGNIFICANCE: Aquatic treadmill walking has
      become a common rehabilitation modality following surgical stabilisation of
      cranial cruciate ligament deficiency. However, evidence-based best practice
      guidelines to enhance stifle kinematics do not exist. Our findings suggest that
      rehabilitation utilising a water level at or above the stifle will achieve the
      best stifle kinematics following surgical stifle stabilisation.

PMID- 29044562
TI  - Myocardial Bridging: A Meta-Analysis of Prevalence.
AB  - The main objective of this article was to analyze prevalence data about
      myocardial bridging (MB) in published studies. To this purpose, we performed a
      meta-analysis of studies published in English literature that contained data
      about the prevalence of MB and its anatomical characteristics. The overall
      prevalence was 19% (CI: 17-21%); autopsy studies revealed an overall prevalence
      of 42% (CI: 30-55%), CT studies 22% (CI: 18-25%), and coronary angiography 6%
      (CI: 5-8%). Most bridges were located on the left anterior descending artery (82%
      overall, 63% on autopsy studies), had a mean thickness of 2.47 mm and a mean
      length of 19.3 mm. In conclusion, autopsy studies should be the gold standard in
      evaluating the actual prevalence of myocardial bridges, while in vivo high
      resolution CT scanning should be preferred to coronary angiography studies.

PMID- 29044563
TI  - The impact of socioeconomic status on stage specific prostate cancer survival and
      mortality before and after introduction of PSA test in Finland.
AB  - Socioeconomic status (SES) has an impact on prostate cancer (PCa) outcomes. Men
      with high SES have higher incidence and lower mortality of PCa versus lower SES
      males. PCa cases diagnosed in Finland in 1985-2014 (N = 95,076) were identified
      from the Finnish Cancer Registry. Information on education level (EL) was
      obtained from Statistics Finland. EL was assessed with three-tiered scale: basic,
      upper secondary and higher education. PCa stage at diagnosis was defined as
      localized, metastatic or unknown. Years of diagnosis 1985-1994 were defined as
      pre-PSA period and thereafter as post-PSA period. We report PCa-specific survival
      (PCSS) and relative risks (RR) for PCa specific mortality (PCSM) among cancer
      cases in Finland, where healthcare is 100% publicly reimbursed and inequality in
      healthcare services low. Men with higher EL had markedly better 10-year PCSS: 68
      versus 63% in 1985-1994 and 90 versus 85% in 1995-2004 compared to basic EL in
      localized PCa. The RR for PCSM among men with localized PCa and higher EL
      compared to basic EL was 0.76(95%confidence interval (CI) 0.66-0.88) in 1985-1994
      and 0.61(95%CI 0.53-0.70) in 1995-2004. Variation in PCSS and PCSM between EL
      categories was evident in metastatic PCa, too. The difference in PCSM between EL
      categories was larger in the first 10-year post-PSA period than before that but
      decreased thereafter in localized PCa, suggesting PSA testing became earlier
      popular among men with high EL. In summary, higher SES/EL benefit PCa survival
      both in local and disseminated disease and the effect of EL was more pronounced
      in early post-PSA period.

PMID- 29044564
TI  - Work is Important. Commentary on Finn et al. (2017) Decisions to Attend and Drink
      at Party Events: The Effects of Incentives and Disincentives and Lifetime Alcohol
      and Antisocial Problems.

PMID- 29044565
TI  - Reclassification of the Rhodomelaceae using High Throughput Sequencing:
      application of big data to algal systematics.

PMID- 29044566
TI  - Erratum.

PMID- 29044567
TI  - Response to the comments on "Analysis of Mobile Phone Use Among Young Patients
      with Brain Tumors in Japan".

PMID- 29044568
TI  - A new single-urea-bound 3,5-dimethylphenylcarbamoylated beta-cyclodextrin chiral
      stationary phase and its enhanced separation performance in normal-phase liquid
      chromatography.
AB  - A new single-urea-bound chiral stationary phase based on 3,5
      dimethylphenylcarbamoylated beta-cyclodextrin was prepared through the Staudinger
      reaction of mono (6A -azido-6A -deoxy)-per(3,5-dimethylphenylcarbamoylated) beta
      cyclodextrin and 3-aminopropyl silica gel under CO2 atmosphere. The new phase
      exhibited good enantioseparation performance for 33 analytes using normal-phase
      HPLC conditions; 19 of them were baseline separated. Effects of structure of
      analytes, alcoholic modifiers, and acidic/basic additives on separation
      performances of this new cyclodextrin chiral stationary phase have been studied
      in detail. The results showed that the retention and resolution of acidic and
      basic analytes on the CSP were greatly affected by the additives. Peak symmetry
      for some analytes could be improved by simultaneously adding acidic and basic
      additives to the mobile phase. This work expands the potential applications of
      the cyclodextrin-based chiral stationary phases in the normal-phase HPLC.

PMID- 29044570
TI  - Corrigendum.

PMID- 29044569
TI  - Bundle sheath lignification mediates the linkage of leaf hydraulics and venation.
AB  - The lignification of the leaf vein bundle sheath (BS) has been observed in many
      species and would reduce conductance from xylem to mesophyll. We hypothesized
      that lignification of the BS in lower-order veins would provide benefits for
      water delivery through the vein hierarchy but that the lignification of higher
      order veins would limit transport capacity from xylem to mesophyll and leaf
      hydraulic conductance (Kleaf ). We further hypothesized that BS lignification
      would mediate the relationship of Kleaf to vein length per area. We analysed the
      dependence of Kleaf , and its light response, on the lignification of the BS
      across vein orders for 11 angiosperm tree species. Eight of 11 species had lignin
      deposits in the BS of the midrib, and two species additionally only in their
      secondary veins, and for six species up to their minor veins. Species with
      lignification of minor veins had a lower hydraulic conductance of xylem and
      outside-xylem pathways and lower Kleaf . Kleaf could be strongly predicted by
      vein length per area and highest lignified vein order (R2  = .69). The light
      response of Kleaf was statistically independent of BS lignification. The
      lignification of the BS is an important determinant of species variation in leaf
      and thus whole plant water transport.

PMID- 29044571
TI  - Sensitivity of sorghum pollen and pistil to high-temperature stress.
AB  - High temperature (HT) decreases seed set percentage in sorghum (Sorghum bicolor
      [L.] Moench). The relative sensitivity of pollen and particularly pistil and the
      mechanistic response that induces tolerance or susceptibility to HT are not well
      known and hence are the major objectives of this research. The male sterile
      (ATx399) and fertile (RTx430) lines were exposed to 30/20  degrees C (optimum
      temperature), 36/26  degrees C (HT1 ), and 39/29  degrees C (HT2 ) from the start
      of booting to seed set in a controlled environment. Similarly, in the field, HT
      stress was imposed using heat tents. HT stress decreased pollen germination.
      Relatively high levels of reactive oxygen species and decreased antioxidant
      enzyme activity and phospholipid unsaturation were observed in pollen compared to
      pistil under HT. The severe cell organelle damage was observed in pollen and
      pistil at 36/26 and 39/29  degrees C, respectively. The seed set percentage was
      higher in HT-stressed pistil pollinated with optimum-temperature pollen. Direct
      and reciprocal crosses indicate that pollen was more sensitive with larger
      decreases in seed set percentage than pistil under HT stress. The negative impact
      was greater in pollen than pistil at lower temperatures. Overall, pollen was more
      sensitive than pistil to HT stress because it is more susceptible to oxidative
      damage than pistil.

PMID- 29044572
TI  - Understanding lay perspectives on socioeconomic health inequalities in Britain: a
      meta-ethnography.
AB  - The links between socioeconomic circumstances and health have been extensively
      studied in Britain but surprisingly few studies consider lay perspectives. This
      is problematic given popular efforts to reduce health inequalities appear to be
      based on assumption that public understanding is limited (this is evident in
      efforts to raise awareness of both 'upstream' causes of health inequalities and
      health-damaging behaviours). The results of this meta-ethnography, involving 17
      qualitative studies, fundamentally challenge this assumption. We show, first,
      that people who are living with socioeconomic disadvantage already have a good
      understanding of the links between socioeconomic hardship and ill-health. Indeed,
      participants' accounts closely mirror the research consensus that material
      structural factors represent 'upstream' determinants of health, while
      'psychosocial' factors provide important explanatory pathways connecting material
      circumstances to health outcomes. Despite this, people living in disadvantaged
      circumstances are often reluctant to explicitly acknowledge health inequalities,
      a finding that we suggest can be understood as an attempt to resist the stigma
      and shame of poverty and poor health and to (re)assert individual agency and
      control. This suggests that work to increase public awareness of health
      inequalities may unintentionally exacerbate experiences of stigma and shame,
      meaning alternative approaches to engaging communities in health inequalities
      discussions are required.

PMID- 29044573
TI  - Higher IGFBP3 is associated with increased incidence of colorectal cancer in
      older men independently of IGF1.
AB  - OBJECTIVE: Insulin-like growth factor 1 (IGF1) has anabolic and growth-promoting
      effects, raising concerns regarding its potential to promote tumour growth.
      Circulating IGF1 is bound to binding proteins, which modulate bioavailability of
      IGF1. This study assessed the associations of IGF1 and its binding proteins 1
      (IGFBP1) and 3 (IGFBP3) with cancer risk. DESIGN: A prospective cohort study of
      4042 men aged >=70 years. METHODS: Plasma total IGF1, IGFBP1 and IGFBP3 were
      measured between 2001 and 2004. Cancer-related outcomes were assessed until 20
      June 2013 using data linkage. Analyses were performed using proportional hazards
      models with death as a competing risk, and adjustments were made for potential
      confounders. Results are expressed as subhazard ratios (SHR). RESULTS: There were
      907 men who were diagnosed with cancer during a median of 9-year follow-up. Of
      these, there were 359, 139 and 125 prostate, colorectal and lung cancers,
      respectively. After adjustments, total IGF1 was not associated with the incidence
      of any cancer, prostate, lung or colorectal cancer. In the fully-adjusted model,
      higher IGFBP3 was associated with increased incidence of colorectal cancer (SHR =
      1.20, 95% CI 1.01-1.43; P = .041 for every 1 standard deviation increase in
      IGFBP3) but not other cancers. This effect was not attenuated by inclusion of
      total IGF1 into the multivariate model (SHR = 1.28, 95% CI 1.03-1.58; P = .025).
      Neither total IGF1, IGFBP1 nor IGFBP3 were associated with cancer-related deaths.
      CONCLUSION: Higher IGFBP3 predicted increased incidence of colorectal cancer in
      older men independent of conventional risk factors and total IGF1. Further
      studies are warranted to explore potential underlying mechanisms.

PMID- 29044574
TI  - Context-Specific Inhibition is Related to Craving in Alcohol Use Disorders: A
      Dangerous Imbalance.
AB  - BACKGROUND: Most contemporary neuroscientific models of alcohol use disorders
      (AUD) incorporate an imbalance between enhanced cue reactivity, which results in
      a strong urge to consume, and the impaired inhibitory control of that urge. While
      these phenomena have been frequently investigated separately, studies involving
      both aspects and thus precisely investigating the postulated imbalance are rare.
      In this study, inhibition was investigated in an addiction-specific context and
      individual craving levels were also examined. METHODS: This study compared
      inhibition in alcohol-related and neutral contexts in patients with AUD and
      healthy controls, while also taking into account the individual amount of
      craving. All subjects performed a Go/NoGo task involving neutral and alcohol
      related NoGo trials, while their brain activity was recorded using multichannel
      electroencephalography. The map strength and topography of the N2 and P3
      components of the NoGo event-related potentials were compared between groups and
      contexts using whole-scalp randomization-based methods. The effects of interest
      were further investigated with sLORETA source analysis. RESULTS: For the N2
      component, the context by craving interaction was strong for map strength and map
      topography. The source analysis indicated that in subjects with high craving,
      alcohol-related context led to enhanced and prolonged activation in the posterior
      cingulate and premotor cortical areas. This interaction was specific for craving,
      but not for diagnostic classification. The amplitude of the P3 component was
      reduced in subjects with AUD, which replicated previous findings. CONCLUSIONS: In
      subjects with strong craving, the conflict reflected in the NoGo-N2 was enhanced
      in the alcohol-related context. Such enhanced conflict probably makes the
      successful inhibition of the urge to drink in high-risk situations even more
      difficult for this subgroup of patients and should therefore be addressed in
      individualized treatment planning.

PMID- 29044575
TI  - Investigation of the effect of astaxanthin on alveolar bone loss in experimental
      periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Astaxanthin is a keto-carotenoid that has a strong
      antioxidant effect. The purpose of this study was to evaluate the effects of
      astaxanthin on alveolar bone loss and histopathological changes in ligature
      induced periodontitis in rats. MATERIAL AND METHODS: Wistar rats were divided
      into four experimental groups: non-ligated (C, n = 6); ligature only (L, n = 6);
      ligature and astaxanthin (1 mg/kg/day astaxanthin, AS1 group, n = 8); ligature
      and astaxanthin (5 mg/kg/day astaxanthin, AS5 group, n = 8). Silk ligatures were
      placed at the gingival margin of lower first molars of the mandibular quadrant.
      The study duration was 11 days and the animals were killed at the end of this
      period. Changes in alveolar bone levels were clinically measured and tissues were
      immunohistochemically examined, osteocalcin, bone morphogenic protein-2,
      inducible nitric oxide synthase, Bax and bcl-2 levels in alveolar bone and
      tartrate-resistant acid phosphatase-positive osteoclast cells, osteoblast and
      inflammatory cell counts were determined. RESULTS: Alveolar bone loss was highest
      in the L group and the differences among the L, AS1 and AS5 groups were also
      significant (P < .05). Both doses of astaxanthin decreased tartrate-resistant
      acid phosphatase-positive+ osteoclast cell and increased osteoblast cell counts
      (P < .05). The inflammation in the L group was also higher than those of the C
      and AS1 groups were (P < .05) indicating the anti-inflammatory effect of
      astaxanthin. Although inducible nitric oxide synthase, osteocalcin, bone
      morphogenic protein-2 and bax staining percentages were all highest in the AS5
      group and bcl-2 staining percentage was highest in the AS1 group, values were
      close to each other (P > .05). CONCLUSION: Within the limits of this study, it
      can be suggested that astaxanthin administration may reduce alveolar bone loss by
      increasing osteoblastic activity and decrease osteoclastic activity in
      experimental periodontitis model.

PMID- 29044576
TI  - Long-term outcomes after hand-sewn versus circular-stapled (25 and 29 mm)
      anastomotic technique after esophagogastrectomy for esophageal cancer.
AB  - BACKGROUND: Anastomotic stricture following esophagogastrectomy (EG) can lead to
      significant dysphagia, necessitating interventions such as endoscopic dilatation.
      These post-operative complications gain importance with the increased survival
      rate of patients after EG. This study aimed to assess the outcomes of both
      circular-stapled (CS: 25 and 29 mm) and hand-sewn (HS) anastomoses after EG.
      METHODS: We reviewed prospectively accrued data from December 2004 to December
      2014 identifying all patients undergoing EG for esophageal cancer. Immediate post
      operative and long-term complications were noted. Primary outcome measures
      included anastomotic leak and stricture, dysphagia, and subsequent. RESULTS: A
      total of 142 patients were identified for analysis. The method used for
      reconstruction was noted: CS-EEA-25 mm (n = 30), CS-EEA-29 mm (n = 30), and HS (n
      = 82). Demographics, tumor pathology, and tumor locations were similar in each
      group. All groups experienced similar rates of anastomotic leak, stricture, and
      dysphagia. Furthermore, post-operative dilations for symptomatic dysphagia were
      required in 3 (10%), 4 (13%), and 9 (11%) patients, P = 0.91. CONCLUSION: In this
      cohort, the method of anastomotic construction had no bearing on the rate of
      complications after EG for the treatment of esophageal cancer. Furthermore, long
      term need for dilations for symptomatic dysphagia was equal among all groups.

PMID- 29044577
TI  - Development and Validation of a Virtual Examination Tool for Firearm Forensics,.
AB  - The transition from 2D imaging to 3D scanning in the discipline of firearms and
      toolmark analysis is likely to provide examiners an unprecedented view of
      microscopic surface topography. The digital examination of measured 3D surface
      topographies has been referred to as virtual microscopy (VM). The approach offers
      several potential advantages over traditional comparison microscopy. Like any new
      analytic method, VM must be validated prior to its use in a crime laboratory.
      This paper describes one of the first validation studies of virtual microscopy.
      Fifty-six participants at fifteen laboratories used virtual microscopic tools to
      complete two proficiency-style tests for cartridge case identification. All
      participating trained examiners correctly reported 100% of the identifications
      (known matches) while reporting no false positives. The VM tools also allowed
      examiners to annotate compared surfaces. These annotations provide insight into
      the types of marked utilized in comparative analysis. Overall, the results of the
      study demonstrate that trained examiners can successfully use virtual microscopy
      to conduct firearms toolmark examination and support the use of the technology in
      the crime laboratory.

PMID- 29044578
TI  - Factors associated with local recurrence after surgery for bone metastasis to the
      extremities.
AB  - BACKGROUND AND OBJECTIVES: With increasing life expectancy of patients with bone
      metastasis, durable surgical stabilization of bone metastasis is necessary. Local
      recurrence (LR) can compromise surgical stabilization and necessitate
      retreatment. We analyzed LR rate and factors associated with LR in patients
      undergoing surgery for bone metastasis. METHODS: Patients (n = 301) who underwent
      surgery for bone metastasis to the extremities were reviewed. Possible factors
      that might be associated with LR were investigated. RESULTS: LR rate was 16%
      (49/301). Surgical margin was associated with LR, as patients with en-bloc
      resection had significantly less LR than patients who underwent curettage (5/66
      vs 44/235, P = 0.03). Prostate cancer had lowest rate (0%) of LR and colon cancer
      had highest rate (31%). Interval from surgery to LR differed among primary cancer
      types (4.5 +/- 3.9 months [lung cancer], vs 12.3 +/- 12.9 months [other cancers],
      P = 0.041). In multivariate analysis, en-bloc surgical margins (HR = 0.372, P =
      0.036) and primary cancers of breast or prostate (HR = 0.391, P = 0.049) were
      independent factors associated with longer LR-free survival. CONCLUSIONS: LR
      after surgery for bone metastasis to extremities is affected by surgical margin
      and primary cancer type. These factors, along with expected patient survival,
      need to be considered when planning surgery for bone metastasis to extremities.

PMID- 29044579
TI  - Doubt and fear of self in bulimia nervosa.
AB  - OBJECTIVE: Several overlapping cognitive processes have been identified in eating
      disorders (EDs) and obsessive compulsive disorder (OCD). Drawing from the OCD
      literature, the present study examined whether bulimia nervosa (BN) is associated
      with a maladaptive inductive reasoning style characterized by the over-investment
      in possibility-based (as opposed to reality-based) information. METHOD: Women
      with BN (n = 25) and healthy controls (HC; n = 24) completed the Inference
      Processes Task (IPT), an ecological inductive reasoning task previously validated
      in OCD samples. Participants also completed the Fear of Self Questionnaire (FSQ)
      that evaluates investment in a feared possible identity. RESULTS: Significant
      differences on the IPT indicate that the BN group was more influenced by
      possibility-based information throughout the task than the HC group (F[5.44,
      255.78] = 6.94, p > .001). It was also found that the BN group scored
      significantly higher on the FSQ than the HC group (t[29.98] = 8.4, p > .001),
      replicating previous findings. Finally, scores on the IPT were significantly
      correlated with measures of symptom severity. DISCUSSION: These findings suggest
      that BN may be associated with maladaptive inductive reasoning processes
      characterized by over-investment in possibility-based feared outcomes and
      identities.

PMID- 29044581
TI  - Women with polycystic ovary syndrome demonstrate worsening markers of
      cardiovascular risk over the short-term despite declining hyperandrogenaemia:
      Results of a longitudinal study with community controls.
AB  - OBJECTIVE: To compare age-associated changes in cardiovascular risk markers in
      lean and obese reproductive-aged women with polycystic ovary syndrome (PCOS) with
      community controls. DESIGN: Longitudinal study at an academic medical centre
      PATIENTS: Patients diagnosed with PCOS by 2004 Rotterdam criteria in a
      multidisciplinary clinic were systematically enrolled from 2006-2014 in a PCOS
      cohort study and subsequently agreed to participate in a longitudinal study. The
      comparison controls were from the prospective, longitudinal Ovarian Aging (OVA)
      study, which consists of healthy women with regular menstrual cycles recruited
      from 2006 to 2011. MEASUREMENTS: Cardiovascular risk markers and hormone
      parameters at baseline and follow-up. RESULTS: Obese and lean PCOS (n = 38) and
      control women (n = 296) completed two study visits. The follow-up time (3.5 +/-
      1.5 vs 4.0 +/- 0.8 years, P = .06) and magnitude of BMI gain (+0.1 kg/m2 /y [
      0.11, 0.36] vs +0.26 [-0.18, 0.87] P = .19) did not differ between obese and lean
      PCOS and controls. In PCOS subjects, total testosterone decreased in both obese
      and lean, but the decrease was greater in obese subjects (-0.09 nmol/L per year;
      95% CI: -0.16, -0.02 vs -0.04 nmol/L per year; 95%CI: -0.11, 0.03). Compared to
      their respective controls, obese and lean PCOS saw worsening triglyceride (TG)
      levels (P < .05) and HOMA-IR (P < .05) over time, but there was no difference in
      change in LDL, HDL, fasting glucose, C-reactive protein or ALT. CONCLUSIONS: In a
      longitudinal study, reproductive-aged women with PCOS demonstrated declines in
      biochemical hyperandrogenaemia over time. Despite this, PCOS subjects experienced
      steeper increases in cardiovascular risk factors associated with insulin
      resistance, including triglycerides and HOMA-IR.

PMID- 29044580
TI  - Low oxytocin levels are related to alexithymia in anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa is associated with social-emotional functioning
      deficits and low levels of the social neurohormone oxytocin, even after weight
      gain. The relationship between low oxytocin levels and social-emotional
      functioning impairment has not been studied. METHOD: We performed a cross
      sectional study of 79 women (19 who were less than 85% of ideal body weight [IBW]
      with anorexia nervosa [AN], 26 who were 90-120% IBW with a history of AN [AN-WR],
      and 34 who were 90-120% IBW with no eating disorder history [H]). We administered
      the Eating Disorder Examination-Questionnaire (EDE-Q), Leibowitz Social Anxiety
      Scale-Self Report (LSAS-SR), Dimensional Assessment of Personality Pathology
      Basic Questionnaire (DAPP-BQ; suspiciousness and insecure attachment subscales),
      and the Toronto Alexithymia Scale (TAS-20). We also analyzed fasting serum
      oxytocin levels. RESULTS: Most measures of social-emotional functioning showed
      impairment in women with AN and AN-WR compared to H. Oxytocin levels were low in
      AN-WR compared to H. Across groups, low oxytocin levels were associated with
      difficulty identifying feelings (r = -.45, p = .008) and overall alexithymia (r =
      -.34, p = .0489). DISCUSSION: We speculate that low oxytocin levels may
      contribute to alexithymia in women with anorexia nervosa.

PMID- 29044582
TI  - Provider views on the management of Ewing sarcoma of the spine and pelvis.
AB  - BACKGROUND: Curative therapy for ES requires both chemotherapy and local control
      of primary tumor. There is no universally accepted standard approach to local
      control modalities. This survey was conducted to determine practice patterns and
      factors influencing the choice to offer various local control modalities to
      patients with ES of the spine and pelvis. METHODS: The survey consisted of four
      scenarios involving a 15-year-old girl who presented with Ewing sarcoma of
      thoracic vertebra, sacrum, iliac wing, and acetabulum with or without neurologic
      compromise. The questionnaire was sent to oncologists, orthopedic surgeons, and
      radiation oncologists, asking their recommendations for local control modality.
      RESULTS: Among 94 respondents, radiotherapy was most frequently chosen for sacral
      tumors (68.1%) and T10 vertebral tumors (46.2%) whereas surgery was preferred for
      iliac wing pelvic tumors (45.7%) and acetabular tumors (43.6%). Orthopedic
      surgeons were significantly more likely to offer surgery than radiation
      oncologists (OR 3.07, 95%CI 1.37-6.88, P = 0.007). Providers outside North
      America were more likely to offer combined surgery plus radiotherapy (OR 10.58,
      95%CI 5.41-20.70, P < 0.001). CONCLUSION: Considerable heterogeneity exists in
      local control modalities for Ewing sarcoma of the spine and pelvis. Specialty and
      location of practice may influence treatment recommendations.

PMID- 29044583
TI  - Hierarchical Archimedean copula models for the analysis of binary familial data.
AB  - Archimedean copulas are commonly used in a wide range of statistical models due
      to their simplicity, manageable analytical expressions, rich choices of generator
      functions, and other workable properties. However, the exchangeable dependence
      structure inherent to Archimedean copulas limits its application to familial
      data, where the dependence among family members is often different. When response
      variables are binary, modeling the familial associations becomes more challenging
      due to the stringent constraints imposed on the dependence parameters. This paper
      proposes hierarchical Archimedean copulas to account for the natural hierarchical
      dependence structure in familial data and addresses the details in the modeling
      of binary familial data and the inference based on maximum likelihood estimate.
      An example showing the flexibility of this powerful tool is also presented with
      possible extension to other similar studies.

PMID- 29044584
TI  - Direct medical costs associated with the extrahepatic manifestations of hepatitis
      C virus infection in France.
AB  - BACKGROUND: The economic impact of extrahepatic manifestations of hepatitis C
      virus (HCV) infection remains unknown for France. AIM: To estimate the prevalence
      of extrahepatic manifestations of HCV and the direct medical costs associated
      with them. METHODS: Estimates of 13 extrahepatic manifestations prevalence were
      obtained from (1) a retrospective data analysis of HCV-infected patients in a
      specialised centre and the baseline prevalence in the general French population
      and (2) an international systematic review. Per-patient-per-year costs to treat
      these manifestations were obtained from the literature, national databases or
      expert opinion. The impact of achieving HCV cure after anti-viral therapy was
      applied to the French healthcare costs. RESULTS: Using approach (1), increased
      prevalence rates in HCV patients compared to the general population were observed
      for most extrahepatic manifestations. The mean per-patient-per-year cost of these
      manifestations in the tertiary centre was 3296 ? [95% CI 1829; 5540]. In France,
      HCV-extrahepatic manifestations amounted to a total cost of 215 million (M) ? per
      year [144; 299]. Using approach (2), the mean per-patient-per-year cost was
      estimated to be 1117 ?. The estimated total cost reduction in France associated
      with HCV cure was 13.9 M? for diabetes, 8.6 M? for cryoglobulinemia vasculitis,
      6.7 M? for myocardial infarction, 2.4 M? for end-stage renal disease and 1.4 M?
      for stroke. CONCLUSION: Extrahepatic manifestations of HCV infection
      substantially add to the overall economic burden of the disease in France. HCV
      cure after anti-viral therapy is expected to significantly reduce the total costs
      of managing these manifestations in France.

PMID- 29044585
TI  - Dental fear among transgender individuals - a cross-sectional survey.
AB  - AIMS: The aims of this study were to: (1) evaluate the level of dental fear among
      transgender individuals and (2) investigate specific predictors of dental fear in
      individuals who identify as transgender. METHOD AND RESULTS: An anonymous survey
      among transgender adults was conducted using both a web-based and paper survey.
      The survey included the Dental Fear Survey (DFS), history of hormonal
      interventions, perceived gender roles, and demographic information. The bivariate
      analyses did not show a significant difference in DFS between sex assigned at
      birth (p = 0.628) or among gender identities (p = 0.109). A regression model
      analysis for the level of DFS by using participants' demographic information as
      independent variables indicated the fear and experience of
      discrimination/maltreatment were significant predictors of dental fear;
      standardized beta coefficients (p-value) were 0.35 (p = 0.017) and 0.28 (p =
      0.041), respectively. CONCLUSION: The fear and experiences of
      discrimination/maltreatment were significantly positively associated with their
      level of dental fear.

PMID- 29044586
TI  - Males with prolactinoma are at increased risk of incident cardiovascular disease.
AB  - OBJECTIVE: To investigate whether the risk of incident cardiovascular disease
      (CVD) is increased in patients with prolactinoma. DESIGN: Population-based,
      retrospective, open-cohort study using The Health Improvement Network (THIN)
      database. PATIENTS: A total of 2233 patients with prolactinoma and 10 355 matched
      controls (1:5 ratio) from UK General Practices contributing to THIN were
      included. Sex, age, body mass index and smoking status were used as matching
      parameters. The primary outcome was any incident CVD, defined by Read codes
      suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic
      attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were
      calculated with Poisson regression, using clinically relevant parameters as model
      covariates. Sensitivity analyses were performed to check whether a change in the
      initial assumptions could have an impact on the findings. RESULTS: During the 6
      year observation period, the composite CVD outcome was recorded in 54 patients
      with prolactinoma and 180 "nonexposed" individuals. The incidence rate was 1.8
      and 14.8 per 1000 person-years for the females and males with prolactinoma,
      respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval
      (CI): 0.61-1.61, P = .968)] in female patients and 1.94 (95% CI: 1.29-2.91, P =
      .001) in male patients. These findings remained robust in sensitivity analyses
      restricting to patients with documented record of dopamine agonist treatment and
      those with newly diagnosed prolactinoma. CONCLUSIONS: In contrast to females, men
      with prolactinoma have increased risk for incident CVD; the aetiology of this
      gender-specific finding remains to be elucidated.

PMID- 29044587
TI  - Weight suppression and bulimic syndrome maintenance: Preliminary findings for the
      mediating role of leptin.
AB  - OBJECTIVE: Longitudinal studies support a prospective relationship between weight
      suppression (WS) and bulimic syndrome (BN-S) maintenance. Although biobehavioral
      mechanisms have been proposed to explain this link, such mechanisms have yet to
      be identified. Given that weight loss would reduce leptin levels which may
      influence eating, this study examined whether reduced leptin levels mediate the
      link between greater WS and longer illness duration. METHOD: Women (N = 53), ages
      18-45 years, were recruited from the community if they met criteria for a BN-S,
      including either DSM-5 bulimia nervosa (BN; n = 33) or purging disorder (PD: n =
      20), and fell within a healthy weight range (18.5-26.5 kg/m2 ). Participants
      completed clinical assessments and provided blood samples to measure circulating
      leptin. RESULTS: Significant associations were found among greater WS, lower
      leptin concentrations, and longer duration of illness. Mediation analyses using
      bootstrapping procedures indicated all paths were significant and that leptin
      mediated the link between WS and illness duration. An alternative model in which
      longer illness duration contributed to leptin, via greater WS, was not supported.
      DISCUSSION: Longitudinal research is needed to support temporal associations and
      explore behavioral mechanisms linking leptin to illness trajectory.

PMID- 29044588
TI  - A uniform method for the simultaneous blood group phenotyping of Fya , Fyb , Jka
      , Jkb , S, s, P1, k applying lateral-flow technique.
AB  - BACKGROUND AND OBJECTIVES: A lateral flow assay for simultaneous blood group
      typing of ABO, RhD, C, E, c, e, Cw and K with stable end-point and without
      centrifugation is in routine use since several years (MDmulticard(r) ). The
      typing of extended phenotype parameters belonging to the Duffy, Kidd, MNSs blood
      group systems and others, however, has not yet been demonstrated for this
      technique. Reliable detection of Fyx , a weak Fyb phenotype with a pronounced
      quantitative reduction of the number of Fyb antigens on the erythrocyte surface,
      remains a weakness of current serological blood grouping techniques. MATERIAL AND
      METHODS: The performance characteristics of the following reagents were evaluated
      in donor and patient samples in lateral flow technology (MDmulticard(r) ): Anti
      Fya , -Fyb , -Jka , -Jkb , -S, -s, -P1 and -k. The sensitivity to detect Fyx was
      in addition evaluated with Fyx positive samples, which had been preselected by
      MALDI-TOF MS-based genotyping. RESULTS: All results obtained with the
      MDmulticard(r) were in full accordance with those of the CE-certified reference
      products for all the eight reagent formulations used: Anti-Fya , -Fyb , -Jka , 
      Jkb , -S, -s, -P1 and -k. Also, all Fyx phenotypes of the selected population of
      93 positive samples, originally identified by MALDI-TOF MS-based genotyping, were
      reliably detected by the lateral flow assay. CONCLUSION: Extended phenotype blood
      group parameters, including the serologically challenging Fyx phenotype, can be
      determined simultaneously, rapidly and accurately using the lateral flow
      (MDmulticard(r) ) technology, even in cases when IgG class antibodies are the
      only source of diagnostic antibodies.

PMID- 29044589
TI  - Unlocking the Unconscious: Exploring the Undiscovered Self.

PMID- 29044590
TI  - Unlocking the Unconscious: Exploring the Undiscovered Self.

PMID- 29044591
TI  - Duodenal localization is a negative predictor of survival after small bowel
      adenocarcinoma resection: A population-based, propensity score-matched analysis.
AB  - BACKGROUND AND OBJECTIVES: This study assessed the influence of tumor
      localization of small bowel adenocarcinoma on survival after surgical resection.
      METHODS: Patients with resected small bowel adenocarcinoma, ACJJ stage I-III,
      were identified from the Surveillance, Epidemiology, and End Results database
      from 2004 to 2013. The impact of tumor localization on overall and cancer
      specific survival was assessed using Cox proportional hazard regression models
      with and without risk-adjustment and propensity score methods. RESULTS:
      Adenocarcinoma was localized to the duodenum in 549 of 1025 patients (53.6%).
      There was no time trend for duodenal localization (P = 0.514). The 5-year cancer
      specific survival rate was 48.2% (95%CI: 43.3-53.7%) for patients with duodenal
      carcinoma and 66.6% (95%CI: 61.6-72.1%) for patients with cancer located in the
      jejunum or ileum. Duodenal localization was associated with worse overall and
      cancer-specific survival in univariable (HR = 1.73; HR = 1.81, respectively; both
      P < 0.001), multivariable (HR = 1.52; HR = 1.65; both P < 0.001), and propensity
      score-adjusted analyses (HR = 1.33, P = 0.012; HR = 1.50, P = 0.002).
      Furthermore, young age, retrieval of more than 12 regional lymph nodes, less
      advanced stage, and married matrimonial status were positive, independent
      prognostic factors. CONCLUSIONS: Duodenal localization is an independent risk
      factor for poor survival after resection of adenocarcinoma.

PMID- 29044592
TI  - Aligning Funding and Need for Family Planning: A Diagnostic Methodology.
AB  - With limited international resources for family planning, donors must decide how
      to allocate their funds to different countries. How can a donor for family
      planning decide whether countries are adequately prioritized for funding? This
      article proposes an ordinal ranking framework to identify under-prioritized
      countries by rank-ordering countries by their need for family planning and
      separately rank-ordering them by their development assistance for family
      planning. Countries for which the rank of the need for family planning is lower
      than the rank of its funding are deemed under-prioritized. We implement this
      diagnostic methodology to identify under-prioritized countries that have a higher
      need but lower development assistance for family planning. This approach
      indicates whether a country is receiving less compared to other countries with
      similar levels of need.

PMID- 29044593
TI  - Patterns of chondrification and ossification in the skull of Graptemys
      pseudogeographica, the false map turtle (Emydidae).
AB  - Patterns of ossification and chondrification are well-described for several
      species of turtles, but details of the chondrocranial anatomy are known for only
      a handful of species. Cleared and double-stained embryos of Graptemys
      pseudogeographica were used to examine the fully formed chondrocranium and the
      formation, chondrification, and ossification of the cranium. The chondrocranium
      of G. pseudogeographica possesses an unusually large, irregularly shaped foramen
      epiphaniale that is joined with the fenestra olfactoria. As in other emydids, and
      many turtles generally, the taenia marginalis is present only as a small
      projection and the taenia medialis is lacking in mature stages of embryonic
      development. Ossification data for G. pseudogeographica are consistent with those
      of other Testudines in that the dentary and maxilla (dermal elements of the upper
      and lower jaws) ossify early, whereas the articular (an endochondral bone of the
      lower jaw) ossifies relatively late. Additionally, comparative ossification shows
      that the vomer is quite variable in its relative timing of ossification across
      Testudines.

PMID- 29044595
TI  - A critical interpretive synthesis: Use of the occupational justice framework in
      research.
AB  - BACKGROUND: The occupational justice framework was established in the late 1990s
      with an agenda to spur occupational therapists to take action against injustices
      pertaining to occupation. METHODS: A critical interpretive synthesis of 23 texts
      was undertaken to examine how the occupational justice framework has been
      utilised in research, with a particular focus on how such research is located on
      a knowledge to action continuum and the extent to which it enacts the call to
      remediate occupational injustices. RESULTS: Within the texts reviewed, the
      occupational justice framework was predominantly used to interpret research
      findings, and only four studies explicitly used an action research approach.
      There was also a dominant tendency to individualise situations of occupational
      justice, but with some examples attending to the social and political production
      of injustices. Absences and silences related to the locations of the research in
      developed regions and a focus on conceptualisations of justice commensurate with
      a Western worldview were evident. CONCLUSIONS: Full realisation of the potential
      contributions of the occupational justice framework requires challenging
      traditional modes of research that focus primarily on knowledge generation, and
      expanding into modes of research that embrace a knowledge to action continuum.
      This expansion, which will enable occupational justice research to more fully
      embrace action-oriented work, requires practicing epistemological reflexivity,
      adopting a critical stance, incorporating a participatory action research
      approach and collaborating with scholars from different disciplines.

PMID- 29044594
TI  - Osteocalcin and osteopontin influence bone morphology and mechanical properties.
AB  - Osteocalcin (OC) and osteopontin (OPN) are major non-collagenous proteins (NCPs)
      involved in bone matrix organization and deposition. In spite of this, it is
      currently unknown whether OC and OPN alter bone morphology and consequently
      affect bone fracture resistance. The goal of this study is to establish the role
      of OC and OPN in the determination of cortical bone size, shape, and mechanical
      properties. Our results show that Oc-/- and Opn-/- mice were no different from
      each other or wild type (WT) with respect to bone morphology (P > 0.1). Bones
      from mice lacking both NCPs (Oc-/- Opn-/- ) were shorter, with thicker cortices
      and larger cortical areas, compared with the WT, Oc-/- , and Opn-/- groups (P <
      0.05), suggesting a synergistic role for NCPs in the determination of bone
      morphology. Maximum bending load was significantly different among the groups (P
      = 0.024), while tissue mineral density and measures of stiffness and strength
      were not different (P > 0.1). We conclude that the removal of both OC and OPN
      from bone matrix induces morphological adaptation at the structural level to
      maintain bone strength.

PMID- 29044596
TI  - Angelicin potentiates TRAIL-induced apoptosis in renal carcinoma Caki cells
      through activation of caspase 3 and down-regulation of c-FLIP expression.
AB  - Preclinical Research & Development Angelicin is a furocoumarin derived from
      Psoralea corylifolia L. fruit that has anti-inflammatory and anti-tumor activity.
      In the present study, the effect of angelicin in enhancing tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL)-induced apoptotic cell death was
      studied in Caki (renal carcinoma) cells. Angelicin alone and TRAIL alone had no
      effect on apoptosis, but in combination these compounds markedly induced
      apoptosis in the cancer cell lines while not inducing apoptosis in normal cells.
      The combination treatment induced accumulation of the sub-G1 population, DNA
      fragmentation, and activated caspase 3 activity in Caki cells, induced down
      regulation of c-FLIP expression post-translationally, and over-expression of c
      FLIP markedly blocked apoptosis induced by combined treatment with angelicin plus
      TRAIL. This study provides evidence that angelicin might be a TRAIL sensitizer.

PMID- 29044597
TI  - Short- and long-term complications of in utero exposure to lamotrigine.
AB  - AIMS: The present study evaluates the effect of antenatal lamotrigine exposure,
      on short- and long-term paediatric outcome. METHODS: The study included the
      children of 83 epileptic women treated with lamotrigine during pregnancy, at a
      tertiary medical centre between 2004-2014. All newborns were monitored for vital
      signs, congenital malformations and Finnegan score. In addition, the parents
      completed a questionnaire regarding their child's development and health up to
      the age of 12 years. RESULTS: No major malformations were found in the newborns.
      None of the newborns had significant withdrawal symptoms by Finnegan score. The
      children were followed-up to the age of 12 years (56.6% were 6-12 years at the
      time of evaluation). There were no significant findings in the incidence of
      neurodevelopmental disorders. CONCLUSIONS: According to our experience,
      lamotrigine is generally safe for pregnancy use, associated with minimal short
      term complications with no long-term effects on the outcome.

PMID- 29044598
TI  - Comparison of common risk stratification indices to predict outcomes among stage
      IV cancer patients with bowel obstruction undergoing surgery.
AB  - BACKGROUND AND OBJECTIVES: Among patients with disseminated malignancy (DMa),
      bowel obstruction is common with high operative morbidity. Since preoperative
      risk stratification is critical, we sought to compare three standard risk
      indices, the American Society of Anesthesiology (ASA) classification, Charlson
      comorbidity index (CCI), and modified frailty index (mFI). METHODS: We identified
      1928 DMa patients with bowel obstruction who underwent an abdominal operation
      from 2007 to 2012 American College of Surgeons National Surgical Quality
      Improvement Program. Multivariate analyses assessed predictors of prolonged
      length of stay (LOS), 30-day serious morbidity and mortality. Receiver operating
      characteristics' areas under the curves (AUCs) for risk indices scores and 30-day
      mortality were assessed. RESULTS: Serious morbidity and mortality rates were
      20.4% and 14.8%. ASA and CCI did not predict serious morbidity or prolonged LOS,
      but were predictors of mortality. The mFI did not predict prolonged LOS, but did
      predict serious morbidity and mortality. Subgroup analyses showed similar
      results. There were no significant differences between ASA, CCI, and mFI AUCs for
      mortality. CONCLUSIONS: ASA, CCI, and mFI are limited in their ability to predict
      postoperative adverse events among DMa patients undergoing surgery for bowel
      obstruction. These data suggest that a more tailored preoperative risk
      stratification tool would improve treatment planning.

PMID- 29044599
TI  - Feedback informed treatment: An empirically supported case study of psychodynamic
      treatment.
AB  - The use of client feedback, via self-report measures of psychological functioning
      and working alliance, is an effective way to improve therapy outcomes. Despite
      this progress, there are many questions about the mechanisms of change for these
      systems. The current study employed a case study approach to examine the
      effectiveness of feedback informed treatment within a psychodynamic therapy. We
      examined the case based on therapy outcomes, alliance processes, and verbatim
      dialogue of in-session exchanges. We also conducted a semistructured interview
      with the therapist to understand how she used and interpreted the feedback within
      her psychodynamic approach. The results demonstrated positive therapy outcomes
      and that feedback assisted with alliance formation, specifically decision making
      about therapeutic tasks and managing negative countertransference. The therapist
      reported that the feedback enhanced her ability to work in the here and now and
      to identify relational patterns. Implications for theory and practice are
      discussed.

PMID- 29044600
TI  - Understanding the client's perspective of helpful and hindering events in
      psychotherapy sessions: A micro-process approach.
AB  - The purpose of this study was to bridge the methodologies of significant events
      and micro-process research to gain a better understanding of clients' perceptions
      of helpful and hindering events in psychotherapy. A total of 16 clients were
      asked to review a recent psychotherapy session and, while watching, complete a
      moment-by-moment rating of helpful/hindrance using a dial rating system. They
      were also asked to describe the most helpful and hindering segments that were
      rated as such. The moment-by-moment ratings suggest that clients perceive a
      significant amount of variability within a single session. The qualitative
      results suggest that clients perceive both specific treatment and common factors
      techniques as being helpful. Further, some of the same therapist actions were
      rated as both helpful and hindering, but they differed in the timing and the
      client's experience of feeling heard and understood versus judged or given advice
      that was not perceived as relevant to them. These results have important
      implications for clinical practice.

PMID- 29044601
TI  - Let's not talk about sex.
AB  - This article uses both a case illustration and data from a large-scale survey of
      outpatient clients (N = 798) to understand the client's perspective about
      avoiding or being dishonest with his or her therapist about sexual topics. The
      case study, of a gay young man working with a heterosexual female therapist,
      explores this client's experience of what happens when it feels impossible to be
      forthcoming about sex and sexuality. Based on the findings of our study, we note
      clients' motives for avoiding these intimate yet important areas (e.g., shame),
      their perception of how this impacts the therapy process (e.g., impedes clinical
      progress), and their sense of therapist responses and attitudes that could
      increase their ability to be more honest ("just ask"). We discuss ways in which
      therapists can facilitate a more open dialogue about sexual material while
      attending to clients' concerns about doing so.

PMID- 29044602
TI  - Severe thrombocytopenia in a patient following liver transplantation caused by
      HPA-1a antibodies produced by the liver donor.

PMID- 29044603
TI  - Preceding functional tooth loss delays recovery from acute cerebral hypoxia and
      locomotor hypoactivity after murine subarachnoid haemorrhage.
AB  - Tooth loss and related changes in the functionality may lead to worse outcome of
      stroke patients, but the effect on hemorrhagic stroke remains unclear. This study
      aimed to determine the impact of impaired masticatory function on acute cerebral
      oxygenation and locomotor activity after experimental subarachnoid haemorrhage
      (SAH). Twenty C57BL/6 mice with (MC-treated group) or without (control group)
      prior treatment of cutting off the upper molars were subjected to SAH by
      endovascular perforation. Grading of SAH and acute cerebral infarction were
      assessed by MR images. Brain tissue oxygen saturation (SbtO2 ) by photoacoustic
      imaging and parameters related to locomotor activity by open-field test were
      analyzed serially after SAH. In all mice, global SbtO2 depression was notable
      immediately after SAH induction (P <.001), which recovered close to the baseline
      levels until day 3. However, MC-treated mice demonstrated a prolonged relative
      cerebral hypoxia (<40% of the baseline SbtO2) as compared to the control (3 +/- 1
      vs 1 +/- 1 days; P <.05). The average distance travelled on day 7 and the ratio
      of central-area distance/total travelled distance by open-field test between days
      7 and 14 were significantly lower in MC-treated mice than in the control mice (P
      <.05), although the occurrences of new infarction were not statistically
      different (P >.05). These data suggest a possible link between preceding
      masticatory impairment and early brain injury to deteriorate neurobehavioural
      function in patients after SAH.

PMID- 29044604
TI  - Epstein-Barr virus-positive mucocutaneous ulcer with a background of Crohn's
      disease and Waldenstrom macroglobulinaemia: a case report highlighting diagnostic
      pitfalls.

PMID- 29044605
TI  - Amputations for extremity soft tissue sarcoma in an era of limb salvage
      treatment: Local control and survival.
AB  - BACKGROUND: Despite multimodality limb salvage treatment (LST) for locally
      advanced extremity soft tissue sarcoma (ESTS), some patients still need an
      amputation. Indications for amputation and oncological outcome for these patients
      are described. METHODS: Between 1996 and 2016, all patients who underwent an
      amputation for ESTS were included. Patients who underwent an amputation as
      primary or as non-primary treatment formed Group I and II, respectively. RESULTS:
      Thirty-nine patients were included, 16 in Group I (41%) and 23 in Group II (59%).
      Tumor size or local recurrence which could not be treated with LST were the two
      main reasons for amputation. Local recurrence free survival (LRFS) (P = 0.396),
      distant metastases free survival (DMFS) (P = 0.965), disease-specific survival
      (DSS) (P = 0.745), and overall survival (OS) (P = 0.718) were comparable for both
      groups. Ten-year LRFS was 90.0% versus 83.7%; DMFS was 31.0% versus 42.2%; DSS
      was 52.2% versus 44.1%; and OS was 44.2% versus 41.6%, for group I and II
      respectively. CONCLUSIONS: Oncological outcome seems to be comparable between
      patients who underwent a primary or a non-primary amputation for ESTS. With the
      on-going possibilities concerning prosthesis and rehabilitation programs, it
      remains important to decide in a multidisciplinary sarcoma team meeting which
      treatment suits best for each individual patient.

PMID- 29044606
TI  - The genetic architecture of photosynthesis and plant growth-related traits in
      tomato.
AB  - To identify genomic regions involved in the regulation of fundamental
      physiological processes such as photosynthesis and respiration, a population of
      Solanum pennellii introgression lines was analyzed. We determined phenotypes for
      physiological, metabolic, and growth related traits, including gas exchange and
      chlorophyll fluorescence parameters. Data analysis allowed the identification of
      208 physiological and metabolic quantitative trait loci with 33 of these being
      associated to smaller intervals of the genomic regions, termed BINs. Eight BINs
      were identified that were associated with higher assimilation rates than the
      recurrent parent M82. Two and 10 genomic regions were related to shoot and root
      dry matter accumulation, respectively. Nine genomic regions were associated with
      starch levels, whereas 12 BINs were associated with the levels of other
      metabolites. Additionally, a comprehensive and detailed annotation of the genomic
      regions spanning these quantitative trait loci allowed us to identify 87
      candidate genes that putatively control the investigated traits. We confirmed 8
      of these at the level of variance in gene expression. Taken together, our results
      allowed the identification of candidate genes that most likely regulate
      photosynthesis, primary metabolism, and plant growth and as such provide new
      avenues for crop improvement.

PMID- 29044607
TI  - Compassion focused therapy: Exploring the effectiveness with a transdiagnostic
      group and potential processes of change.
AB  - OBJECTIVES: This study aimed to examine the effectiveness of a compassion focused
      therapy (CFT) group with a transdiagnostic population, as compared to treatment
      as usual (TAU). A secondary aim was to explore the potential processes of change
      within the treatment. DESIGN: A non-randomized control trial was used. METHOD:
      Fifty-eight participants who engaged in group CFT were compared to 29
      participants receiving TAU. Group CFT consisted of 14 sessions twice weekly for 5
      weeks and once weekly for 4 weeks. Participants completed measures of
      psychopathology, shame, self-criticism, fears of self-compassion, and social
      safeness, at pre-treatment, post-treatment, and 2-month follow-up. Potential
      processes of change were examined using correlations and regression analysis.
      RESULTS: Significantly greater improvements were found for levels of
      psychopathology, fears of self-compassion and social safeness for CFT, compared
      to TAU. Additionally, analyses showed improvements in shame and self-criticism
      within the CFT group but not the TAU group. All improvements were maintained at 2
      month follow-up. Improvements in psychopathology were predicted by changes in
      self-criticism and fears of self-compassion. CONCLUSION: Compassion focused
      therapy appears to be an effective group intervention for a range of mental
      health difficulties. The positive impact of the CFT model with a transdiagnostic
      group emphasizes the value of addressing underlying psychological process, rather
      than symptoms alone. PRACTITIONER POINTS: Compassion focused therapy is a
      multimodal therapy designed to target high levels of shame and self-criticism.
      Compassion focused therapy has been shown previously to have positive results
      within a range of diagnostic-specific populations. While there is an emerging
      research base, limited studies assessing effectiveness with transdiagnostic
      populations have been published. CFT was shown to have a significant effect in
      reducing levels of psychopathology, compared to TAU. A number of potential
      processes of change were identified: Changes in psychopathology were
      significantly correlated with changes in self-criticism and fears of self
      compassion.

PMID- 29044609
TI  - Phenomics allows identification of genomic regions affecting maize stomatal
      conductance with conditional effects of water deficit and evaporative demand.
AB  - Stomatal conductance is central for the trades-off between hydraulics and
      photosynthesis. We aimed at deciphering its genetic control and that of its
      responses to evaporative demand and water deficit, a nearly impossible task with
      gas exchanges measurements. Whole-plant stomatal conductance was estimated via
      inversion of the Penman-Monteith equation from data of transpiration and plant
      architecture collected in a phenotyping platform. We have analysed jointly 4
      experiments with contrasting environmental conditions imposed to a panel of 254
      maize hybrids. Estimated whole-plant stomatal conductance closely correlated with
      gas-exchange measurements and biomass accumulation rate. Sixteen robust
      quantitative trait loci (QTLs) were identified by genome wide association studies
      and co-located with QTLs of transpiration and biomass. Light, vapour pressure
      deficit, or soil water potential largely accounted for the differences in allelic
      effects between experiments, thereby providing strong hypotheses for mechanisms
      of stomatal control and a way to select relevant candidate genes among the 1-19
      genes harboured by QTLs. The combination of allelic effects, as affected by
      environmental conditions, accounted for the variability of stomatal conductance
      across a range of hybrids and environmental conditions. This approach may
      therefore contribute to genetic analysis and prediction of stomatal control in
      diverse environments.

PMID- 29044610
TI  - Molecular improvement of alfalfa for enhanced productivity and adaptability in a
      changing environment.
AB  - Due to an expanding world population and increased buying power, the demand for
      ruminant products such as meat and milk is expected to grow substantially in
      coming years, and high levels of forage crop production will therefore be a
      necessity. Unfortunately, urbanization of agricultural land, intensive
      agricultural practices, and climate change are all predicted to limit crop
      production in the future, which means that the development of forage cultivars
      with improved productivity and adaptability will be essential. Because alfalfa
      (Medicago sativa L.) is one of the most widely cultivated perennial forage crops,
      it has been the target of much research in this field. In this review, we discuss
      progress that has been made towards the improvement of productivity, abiotic
      stress tolerance, and nutrient-use efficiency, as well as disease and pest
      resistance, in alfalfa using biotechnological techniques. Furthermore, we
      consider possible future priorities and avenues for attaining further
      enhancements in this crop as a means of contributing to the realization of food
      security in a changing environment.

PMID- 29044611
TI  - Comparative copper sensitivity between life stages of common subantarctic marine
      invertebrates.
AB  - The development of environmental guidelines in the Antarctic and subantarctic is
      essential, because expansion of research, tourism, and fishing is placing these
      regions at increasing risk of contamination. Data are currently insufficient to
      create the region-specific guidelines needed for the unique conditions in these
      areas. To develop the most appropriate environmental guidelines, data from the
      most sensitive life stages of a species should be included to ensure effective
      protection throughout its life cycle. It is generally accepted that early life
      stages are more sensitive to contaminants. We compared the toxicity of copper
      between juvenile and adult life stages of 4 subantarctic marine invertebrates
      using sublethal and lethal endpoints. For 2 of the species tested, juveniles were
      more sensitive than adults. (The 7-d median effect concentration [EC50] values
      for the gastropod Laevilittorina caliginosa were 79 MUg/L at the juvenile stage
      and 125 MUg/L at the adult; for the flatworm Obrimoposthia ohlini, values were
      190 MUg/L at the juvenile stage and 300 MUg/L at the adult.) For the isopod
      Limnoria stephenseni, juveniles were either more sensitive or of equal
      sensitivity to adults (7-d EC50 values: juvenile 278 MUg/L and adult 320 MUg/L).
      In contrast, for the bivalve Gaimardia trapesina, adults appeared to be more
      sensitive than young adults (7-d EC50 values: juvenile 23 MUg/L and adult <10-20
      MUg/L). Although no consistent trend in the sensitivity of life history stages
      was observed, the present study contributes important information for the
      development of water quality guidelines in polar regions. Environ Toxicol Chem
      2018;37:807-815. (c) 2017 SETAC.

PMID- 29044608
TI  - Nutrient sensing in pancreatic islets: lessons from congenital hyperinsulinism
      and monogenic diabetes.
AB  - Pancreatic beta cells sense changes in nutrients during the cycles of fasting and
      feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal
      beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or
      diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one
      form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a
      decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In
      contrast, inactivating mutations of GCK result in diabetes, including a mild form
      (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM)).
      Mutations of beta cell ion channels involved in insulin secretion regulation also
      alter glucose sensing. Activating or inactivating mutations of ATP-dependent
      potassium (KATP ) channel genes result in severe but completely opposite clinical
      phenotypes, including PNDM and CHI. Mutations of the other ion channels,
      including voltage-gated potassium channels (Kv 7.1) and voltage-gated calcium
      channels, also lead to abnormal glucose sensing and CHI. Furthermore, amino acids
      can stimulate insulin secretion in a glucose-independent manner in some forms of
      CHI, including activating mutations of the glutamate dehydrogenase gene, HDAH
      deficiency, and inactivating mutations of KATP channel genes. These genetic
      defects have provided insight into a better understanding of the complicated
      nature of beta cell fuel-sensing mechanisms.

PMID- 29044612
TI  - Is there an occupational therapy employment crisis within Australia? An
      investigation into two consecutive cohorts of occupational therapy graduates from
      a single Victorian University identifying trends in employment.
AB  - BACKGROUND: Within the context of growing concerns about a potential oversupply
      of occupational therapist, this research examines when, where and how long new
      graduates take to gain employment and identifies influences upon the health and
      university systems. METHOD: A mixed method research design, using an online
      survey was adopted to investigate the topic. Two consecutive cohorts of graduates
      from a single university program were invited to participate. RESULTS: Seventy
      five (58%) responses were received, with 63 (84%) currently employed in an
      occupational therapy role. Of the 12 (16%) not employed, only 3 (4%) described
      themselves as actively seeking employment in an occupational therapy role. A wide
      spread of employment settings and scope of practice areas was reported.
      CONCLUSION: Findings suggest that occupational therapy graduates are gaining
      employment in a range of settings and practice areas, relatively quickly. This
      research adds evidence to the conversation around graduate employment within a
      region of Australia. The Australian population, health system and university
      changes are possible factors influencing employment. The research reveals the
      difficulties in understanding the current situation with limitations in data
      collected, varied terminology and an ever changing job seeking environment. The
      research provides a starting point for the occupational therapy profession to
      further understand the directions the profession is taking. University programs
      may also benefit by using the research to tailor course content to assist
      graduates in gaining employment or to present students with the prospects of new
      employment opportunities.

PMID- 29044614
TI  - ESHHS Conference, July 12-14, 2017, in collaboration with SISS, University of
      Bari Aldo Moro.

PMID- 29044615
TI  - Report of the 49th Annual Meeting of Cheiron: The International Society for the
      History of the Behavioral and Social Sciences.

PMID- 29044613
TI  - Effect of androgen deprivation therapy on the contractile properties of type I
      and type II skeletal muscle fibres in men with non-metastatic prostate cancer.
AB  - The contractile properties of vastus lateralis muscle fibres were examined in
      prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and
      in age- and activity-matched healthy male subjects (Control). Mechanically
      skinned muscle fibres were exposed to a sequence of heavily Ca2+ -buffered
      solutions at progressively higher free [Ca2+ ] to determine their force-Ca2+
      relationship. Ca2+ -sensitivity was decreased in both type I and type II muscle
      fibres of ADT subjects relative to Controls (by -0.05 and -0.04 pCa units,
      respectively, P < .02), and specific force was around 13% lower in type I fibres
      of ADT subjects than in Controls (P = .02), whereas there was no significant
      difference in type II fibres. Treatment with the reducing agent dithiothreitol
      slightly increased specific force in type I and type II fibres of ADT subjects
      (by ~2%-3%, P < .05) but not in Controls. Pure type IIx fibres were found
      frequently in muscle from ADT subjects but not in Controls, and the overall
      percentage of myosin heavy chain IIx in muscle samples was 2.5 times higher in
      ADT subjects (P < .01). The findings suggest that testosterone suppression can
      negatively impact the contractile properties by (i) reducing Ca2+ -sensitivity in
      both type I and type II fibres and (ii) reducing maximum specific force in type I
      fibres.

PMID- 29044616
TI  - FHHS NEWS.

PMID- 29044617
TI  - News and Notes: Conferences.

PMID- 29044618
TI  - Ultrasonographic screening for subclinical osteochondrosis of the femoral
      trochlea in foals (28-166 days old): a prospective farm study.
AB  - BACKGROUND: Extensive osteochondritis dissecans (OCD) lesions of the lateral
      ridge of the trochlea of the femur (LRTF), the most common OCD-affected site in
      the stifle, have a poor outcome with surgical debridement and can be career
      ending. The early detection of osteochondrosis lesions and their conservative
      management holds the promise to enhance outcome. We hypothesise that
      ultrasonography is a valuable field screening tool to detect and monitor early
      subclinical LRTF osteochondrosis. OBJECTIVES: The goals were to 1) describe the
      normal ultrasonographic features of the LRTF in foals of different ages and 2)
      screen a foal cohort at the farm for early subclinical osteochondrosis lesions.
      STUDY DESIGN: Prospective cohort study. METHODS: The LRTF of both hindlimbs of
      Thoroughbred foals (n = 46, 27-166 days old) were imaged once with
      ultrasonography and radiography (lateromedial and caudolateral-craniomedial
      oblique views). Cartilage thickness, ossification front indentation of the
      chondro-osseous junction and epiphyseal vascularisation were assessed on
      ultrasonography. Follow-up radiographs were taken as yearlings. RESULTS: The
      cartilage thickness, ossification front indentation and epiphyseal
      vascularisation significantly decreased with advancing maturity. Subclinical
      osteochondrosis lesions, characterised by semicircular indentations in the
      ossification front (indirect evidence of focal failure of ossification and
      retained cartilage) were detected in six foals (28-145 days old), both with
      radiography and ultrasonography. Ultrasonography provided a better overall
      subjective assessment of the osteochondrosis lesion topography (length, depth and
      the width) compared with radiography. MAIN LIMITATIONS: Post-mortem validation of
      lesions was not possible. CONCLUSION: Ultrasonography of the LRTF is a practical,
      inexpensive and reliable technique to discriminate physiological from
      pathological events at the LRTF in young foals. It revealed the complex
      topography of the chondro-osseous junction permitting a rapid, comprehensive
      assessment of the subclinical osteochondrosis lesions in very young foals.

PMID- 29044619
TI  - Variation in crocodilian dorsal scute organization and geometry with a discussion
      of possible functional implications.
AB  - Dermal ossifications, including osteoderms, are present in many vertebrates and
      are frequently interpreted as a defense against predators. Nevertheless,
      osteoderms remain ubiquitous in adult crocodilians while being absent in
      hatchlings, even though adults rarely experience predation. In other biological
      systems, increased variation, particularly fluctuating asymmetry, have proven
      useful for identifying biological structures likely to have evolved under relaxed
      selection, which in turn may inform their function. Therefore, using the
      keratinous scutes as proxies for the underlying osteoderm morphology, I
      investigated the average intraspecific variability of geometry and fluctuating
      asymmetry in dorsal scutes in five species of crocodilians. I first tested for
      differences in variability of scute length and width, then for differences in
      bilateral fluctuating asymmetry of scute number, before finally investigating
      scute distribution patterns for each species compared to hypothetical rectangular
      and hexagonal scute arrangements. The American crocodile, Crocodylus acutus,
      shows significantly more asymmetry than other species, which is consistent with
      relaxed selection on osteoderms in this species. A suspected decrease in
      intraspecific aggression within Crocodylus acutus, in conjunction with the
      inferred relaxed selection, suggests that, in general, crocodilian osteoderms
      function primarily as defensive armor in aggressive encounters with conspecifics.
      The smooth-fronted caiman, Paleosuchus trigonatus, exhibits increased variation
      in scute dimensions linked to the mediolateral offset of osteoderms in adjacent
      rows, possibly resulting in a more rigid carapace. Unfortunately, comparative
      data on crocodilian behavior, physiology, and development is extremely limited
      and restricts the ability to explore other potential explanations for the
      patterns observed, highlighting the need for more research on rare and cryptic
      crocodylians.

PMID- 29044620
TI  - Science: How the Status Quo Harms its Cultural Authority.
AB  - Three distinct explanatory models are described which underpin the relationship
      between the cultural authority of science and public trust. This essay describes
      how current discourses framed around how the enterprise of science is undertaken;
      damage these models, diminishing knowledge-attitudes, alienating the public while
      reducing the cultural meaning of science.

PMID- 29044621
TI  - Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol
      exposure-induced liver injury.
AB  - Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol
      consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA)
      signaling system that protects the liver from toxic injury. The present study was
      designed to investigate the role of the hepatic GABA signaling system in the
      process of acute ethanol exposure-induced liver injury. Our results showed that
      the expression of GABA synthesizing enzyme glutamic acid decarboxylase and type A
      GABA receptor (GABAA R) subunits was upregulated in ethanol-treated mice compared
      with saline-treated controls. Remarkably, pretreatment of mice with GABA (1.5 mg
      kg-1 body weight, intraperitoneal injection [i.p.]) or with the GABAA R agonist
      muscimol (1.2 mg kg-1 body weight, i.p.) protected the liver against ethanol
      toxicity and improved liver function, whereas pretreatment of mice with the GABAA
      R antagonist bicuculline (2.0 mg kg-1 body weight, i.p.) worsened the liver
      function. Further analyses suggest that GABAA R-mediated signaling protects the
      liver from ethanol injury by, at least partially, inhibiting the IRE1alpha-ASK1
      JNK pro-apoptotic pathway in hepatocytes in the process of ethanol-induced
      endoplasmic reticulum stress response.

PMID- 29044622
TI  - Sonographic diagnosis of neuritis ossificans of the median nerve.
AB  - We report the sonographic appearance of a rare case of neuritis ossificans of the
      median nerve at the wrist, which appeared as a hyperechoic lesion around the
      nerve. Diagnosis was confirmed with magnetic resonance imaging (MRI).

PMID- 29044623
TI  - Retention behavior of flavonoids on immobilized artificial membrane
      chromatography and correlation with cell-based permeability.
AB  - The aim of the study was to investigate the immobilized artificial membrane (IAM)
      retention mechanism for a set of flavonoids and to evaluate the potential of IAM
      chromatography to model Caco-2 permeability. For this purpose, the retention
      behavior of 41 flavonoid analogs on two IAM stationary phases, IAM.PC.MG and
      IAM.PC.DD2, was investigated. Correlations between retention factors, logkw(IAM)
      and octanol-water partitioning (logP) were established and the role of hydroxyl
      groups of flavonoids to the underlying retention mechanism was explored. IAM
      retention and logP values were used to establish sound linear models with Caco-2
      permeability (logPapp ) taken from the literature. Both stepwise regression and
      multivariate analysis confirmed the contribution of hydrogen bond descriptors, as
      additional parameters in the either logkw(IAM) or logP models. Retention factors
      on both IAM stationary phases showed comparable performance with n-octanol-water
      partitioning towards Caco-2 permeability.

PMID- 29044624
TI  - Effect of Chronic Alcohol Abuse on Anabolic and Catabolic Signaling Pathways in
      Human Skeletal Muscle.
AB  - BACKGROUND: Animal studies showed that alcoholic myopathy is characterized by the
      reduction in myofiber cross-sectional area (CSA) and by impaired anabolic
      signaling. The goal of this study was to compare changes in CSA and fiber type
      composition with modifications in anabolic and catabolic signaling pathways at
      the early stages of alcohol misuse in humans. METHODS: Skeletal muscle samples
      from 7 male patients with chronic alcohol abuse (AL; 47.7 +/- 2.0 years old;
      alcohol misuse duration 7.7 +/- 0.6 years) were compared with muscle from a
      control group of 7 healthy men (C; 39.7 +/- 5.0 years old). Biopsies from vastus
      lateralis muscles were taken and analyzed for the changes in fiber type
      composition, fiber CSA, and for the alterations in anabolic and catabolic
      signaling pathways. RESULTS: AL patients did not have detectable clinical
      myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast
      fibers was increased. There was a significant decrease in IGF-1 in plasma and IRS
      1 protein content in muscle of AL group. Levels of total and phosphorylated
      p70S6K1, GSK3beta, and p90RSK1 were not different between AL and C groups. Muscle
      of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of
      anabolic pathway p-4E-BP1 was decreased, while catabolic markers (MuRF-1, MAFbx,
      ubiquitinated proteins) were increased in AL patients when compared with C group.
      CONCLUSIONS: At the early stages of alcohol misuse in humans, changes in the
      regulation of anabolic and catabolic signaling pathways precede the development
      of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic
      myopathy.

PMID- 29044625
TI  - Toward an automated analysis of exchange pathways in spin-coupled systems.
AB  - Understanding (super-)exchange coupling between local spins is an important task
      in theoretical chemistry and solid-state physics. We show that a Green's-function
      approach introduced earlier (Liechtenstein et al., J. Phys. F 1984, 14, L125;
      Steenbock et al., J. Chem. Theory Comput. 2015, 11, 5651) can be used for
      analyzing exchange coupling pathways in an automated fashion rather than by
      visual inspection of molecular orbitals. We demonstrate the capabilities of this
      approach by comparing it to previously published pathway analyses for hydroxy
      bridged dinuclear copper complexes and an oxo-bridged dinuclear manganese
      complex, and employ it for discriminating between through-space and through-bond
      pathways in a naphthalene-bridged bisnickelocene complex. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29044626
TI  - The cost-effectiveness of cognitive behavioral therapy for bulimia nervosa in the
      Australian context.
AB  - OBJECTIVE: This study was to model the cost-effectiveness of specialist-delivered
      cognitive behavioral therapy for bulimia nervosa (CBT-BN) compared to no
      intervention within the Australian context. METHOD: An illness-death model was
      developed to estimate the cost per disability-adjusted life-year (DALY) averted
      of CBT-BN over 2 years from the healthcare perspective. Target population was
      adults aged 18-65 years with BN. Results are reported as incremental cost
      effectiveness ratios (ICER) in 2013 Australian dollars per DALY averted.
      Uncertainty and sensitivity analyses were conducted to test the robustness of
      results. RESULTS: Primary analysis indicated that CBT-BN was associated with
      greater DALY averted (0.10 DALY per person) and higher costs ($1,435 per person)
      than no intervention, resulting the mean ICER of $14,451 per DALY averted (95%
      uncertainty interval [UI]: $8,762 to $35,650). Uncertainty analysis indicated CBT
      BN is 99% likely to be cost-effective at a threshold of $50,000 per DALY averted.
      Including the patients' time and travel costs resulted in the mean ICER of
      $18,858 per DALY averted (95% UI: $11,235 to $46,026). Sensitivity analysis
      indicated the intervention was not cost-effective if over 80% people discontinued
      treatment. Other analyses including a reduced time horizon, increased remission
      rates, and 4-month effect size of CBT-BN increases the ICERs but these ICERs
      remained well below under a threshold of $50,000 per DALY averted. CONCLUSION:
      This study has demonstrated that CBT-BN for adults with BN is a cost-effective
      treatment intervention. Further research is required to investigate the
      practicability of CBT-ED and the cost-effectiveness of other formats of CBT-BN
      delivery.

PMID- 29044627
TI  - Managing, making sense of and finding meaning in advanced illness: a qualitative
      exploration of the coping and wellbeing experiences of patients with lung cancer.
AB  - Coping plays an essential role in maintaining the wellbeing of patients with
      cancer. A number of different coping responses and strategies have been
      identified in the literature. The value and relevance of meaning based coping
      theory has also been emphasised, including Antonovosky's Sense of Coherence (SoC)
      theory. Ten patients with advanced lung cancer were interviewed up to three
      times. A total of twenty in depth interviews were carried out, fully transcribed
      and data were analysed following a methodology of Interpretative Phenomenological
      Analysis. Three broad domains were identified to categorise the core life
      concerns of participants; making sense of and managing one's illness; maintaining
      daily life and relationships and confronting the future. Within these domains
      multiple coping themes are identified, which to varying degrees help to maintain
      patient wellbeing and quality of life. This article considers the relevance of
      SoC theory for understanding the coping experiences of patients with advanced
      cancer, and identifies resources and factors likely to support patient coping,
      with implications for health and social care services.

PMID- 29044629
TI  - Clean pure shift 2D J-resolved spectroscopy.
AB  - 2D J-resolved spectroscopy is one of the oldest and conceptually most elegant
      ways to separate homonuclear scalar couplings from chemical shift information. In
      practice, the classical experiment suffers from a number of complications that
      limits accuracy and resolution, including phasetwist lineshapes, strong coupling
      artifacts, and the need for shearing the spectrum by 45 degrees  to obtain a
      (J,delta)-representation. Here, a novel pure shift 2DJ experiment based on the
      TSE-PSYCHE experiment is reported that deals with all these issues. Previous
      experiments proposed z-filtration to avoid excessive artifacts caused by chunked
      pure shift acquisition. It will be shown that these artifacts can also easily be
      avoided by means of the Pell-Keeler method. As opposed to its z-filtered
      counterparts, the new experiment provides pure shift 2DJ spectra that are free of
      artifacts from pulse imperfections and minimize responses related to strong
      coupling. In this way, multiplet analysis becomes possible at maximal resolution
      and a minimum of spectral complications.

PMID- 29044628
TI  - Possible pro-inflammatory role of heparin-binding epidermal growth factor-like
      growth factor in the active phase of systemic sclerosis.
AB  - Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a
      member of the EGF family growth factors, which affects multiple aspects of the
      wound healing process such as epithelialization, wound contraction and
      angiogenesis. In our study, we measured the serum HB-EGF levels of 51 systemic
      sclerosis (SSc) patients, which showed a significant increase compared with those
      of 20 normal subjects. Further analysis revealed a positive correlation between
      the HB-EGF level and pulmonary ground-glass score but no correlation between the
      former and pulmonary fibrosis score. Other findings include: a significant
      increase of serum sialylated carbohydrate antigen KL-6 levels and significant
      shortness of disease duration in the diffuse cutaneous SSc patients with elevated
      HB-EGF levels; and significantly higher HB-EGF levels in the presence of
      Raynaud's phenomenon, in that of telangiectasia, and in the absence of
      contracture of phalanges in all SSc patients. We then evaluated HB-EGF mRNA
      levels of fibroblasts harvested from skin samples of the SSc patients and those
      of foreskin-derived fibroblasts treated with transforming growth factor-beta,
      both of which were significantly higher than each control. In conclusion, we
      speculate that HB-EGF plays a pro-inflammatory role in the active skin and lung
      lesions of SSc.

PMID- 29044630
TI  - Fully automatic deformable registration of pretreatment MRI/CT for image-guided
      prostate radiotherapy planning.
AB  - PURPOSE: In prostate radiotherapy, dose distribution may be calculated on CT
      images, while the MRI can be used to enhance soft tissue visualization.
      Therefore, a registration between MR and CT images could improve the overall
      treatment planning process, by improving visualization with a demonstrated
      interobserver delineation variability when segmenting the prostate, which in turn
      can lead to a more precise planning. This registration must compensate for
      prostate deformations caused by changes in size and form between the acquisitions
      of both modalities. METHODS: We present a fully automatic MRI/CT nonrigid
      registration method for prostate radiotherapy treatment planning. The proposed
      registration methodology is a two-step registration process involving both a
      rigid and a nonrigid registration step. The registration is constrained to
      volumes of interest in order to improve robustness and computational efficiency.
      The method is based on the maximization of the mutual information in combination
      with a deformation field parameterized by cubic B-Splines. RESULTS: The proposed
      method was validated on eight clinical patient datasets. Quantitative evaluation,
      using Hausdorff distance between prostate volumes in both images, indicated that
      the overall registration errors is 1.6 +/- 0.2 mm, with a maximum error of less
      than 2.3 mm, for all patient datasets considered in this study. CONCLUSIONS: The
      proposed approach provides a promising solution for an effective and accurate
      prostate radiotherapy treatment planning since it satisfies the desired clinical
      accuracy.

PMID- 29044631
TI  - Frailty, hospital volume, and failure to rescue after head and neck cancer
      surgery.
AB  - OBJECTIVES/HYPOTHESIS: We previously reported that high-volume hospital head and
      neck cancer (HNCA) surgical care is associated with decreased mortality, largely
      explained by reduced rates of failure to rescue. Frailty is an independent
      predictor of mortality, but is significantly less likely in patients receiving
      high-volume care. We investigate whether differences in frailty rates explain the
      relationship between volume and outcomes in HNCA patients and whether frailty
      confounds the relationship between failure to rescue and mortality. STUDY DESIGN:
      Cross-sectional analysis. METHODS: Discharge data from the Nationwide Inpatient
      Sample for 159,301 patients who underwent ablative surgery for a malignant oral
      cavity, laryngeal, hypopharyngeal, or oropharyngeal neoplasm in 2001 to 2010 were
      analyzed using cross-tabulations and multivariate regression. Failure to rescue
      was defined as death after a major complication. Frailty was defined using
      frailty-defining diagnosis clusters from the Johns Hopkins Adjusted Clinical
      Groups frailty-defining diagnosis indicator. RESULTS: High-volume hospital care
      was associated with a lower odds of frailty (odds ratio [OR]: 0.7 [95% confidence
      interval [CI]: 0.5-1.0]). Frail patients had higher odds of postoperative
      complications (OR: 4.1 [95% CI: 3.4-4.9]) and mortality (OR: 2.0 [95% CI: 1.3
      3.2]), but no difference in failure to rescue rates (OR: 1.0 [95% CI: 0.6-1.6]).
      High-volume care was not associated with differences in odds of complications
      (OR: 1.0 [95% CI: 0.8-1.2]), but was associated with significantly decreased odds
      of mortality (OR: 0.6 [95% CI: 0.5-0.9]) and failure to rescue (OR: 0. 6 [95% CI:
      0.3-1.0]), which was not attenuated by adjusting for frailty. CONCLUSIONS: High
      volume HNCA surgical care is associated with a significantly lower odds of
      mortality, which appears to be associated with differences in the response to and
      management of complications rather than differences in frailty or complication
      rates. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1365-1370, 2018.

PMID- 29044632
TI  - Fast multiresolution data acquisition for magnetic particle imaging using
      adaptive feature detection.
AB  - PURPOSE: Magnetic particle imaging is a tomographic imaging modality capable of
      determining the distribution of magnetic nanoparticles with high temporal
      resolution. The spatial resolution of magnetic particle imaging is influenced by
      the gradient strength of the selection field used for spatial encoding. By
      increasing the gradient strength, the spatial resolution is improved, but at the
      same time the imaging volume decreases. For a high-resolution image of an
      extended field-of-view, a multipatch approach can be used by shifting the
      sampling trajectory in space. As the total imaging timescales with the number of
      patches, the downside of the multipatch method is the degradation of the temporal
      resolution. METHODS: The purpose of this work was to develop a scanning procedure
      incorporating the advantages of imaging at multiple gradient strengths. A low
      resolution overview scan is performed at the beginning followed by a small number
      of high-resolution scans at adaptively detected locations extracted from the low
      resolution scan. RESULTS: By combining all data during image reconstruction, it
      is possible to obtain a large field-of-view image of anisotropic spatial
      resolution. It is measured in a fraction of time compared to a fully sampled high
      resolution field of view image. CONCLUSIONS: Magnetic particle imaging is a
      flexible imaging method allowing to rapidly scan small volumes. When scaling
      magnetic particle imaging from small animal to human applications, it will be
      essential to keep the acquisition time low while still capturing larger volumes
      at high resolution. With our proposed adaptive multigradient imaging sequence, it
      is possible to capture a large field of view while keeping both the temporal and
      the spatial resolution high.

PMID- 29044633
TI  - Extensive nail changes in a toddler with multisystemic Langerhans cell
      histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various
      organs. Nail changes in LCH are extremely rare. We present this case report of
      extensive nail changes in an 18-month-old child with multisystem LCH.

PMID- 29044634
TI  - Rituximab for the treatment of type B insulin resistance syndrome: a case report
      and review of the literature.
AB  - BACKGROUND: Type B insulin resistance syndrome is a rare disease characterized by
      refractory transient hyperglycaemia and severe insulin resistance associated with
      circulating anti-insulin receptor antibodies. A standardized treatment regimen
      for type B insulin resistance syndrome has yet to be established. CASE REPORT: We
      report the case of a 64-year-old man undergoing haemodialysis for antineutrophil
      cytoplasmic antibody-associated vasculitis and diabetic nephropathy, who
      developed rapid onset of hyperglycaemia (glycated albumin 52.1%). Type B insulin
      resistance syndrome was diagnosed, on the basis of positivity for anti-insulin
      receptor antibodies and the man's autoimmune history of antineutrophil
      cytoplasmic antibody-associated vasculitis and idiopathic thrombocytopenic
      purpura. Although severe hyperglycaemia persisted in spite of corticosteroids and
      high-dose insulin therapy, rituximab treatment resulted in remarkable improvement
      of the man's severe insulin resistance and disappearance of anti-insulin receptor
      antibodies without any adverse effects. CONCLUSIONS: According to a literature
      review of 11 cases in addition to the present case, rituximab appears to be a
      safe and effective strategy for the treatment of corticosteroid-resistant type B
      insulin resistance syndrome.

PMID- 29044635
TI  - Development and application of a real-time polymerase chain reaction assay for
      detection of a novel gut bacteriophage (crAssphage).
AB  - crAssphage is a novel and by far the most abundant bacteriophage in human gut.
      This bacteriophage might modulate gut microbiota balance so as to be involved in
      some diseases like obesity, diabetes, metabolic disorders, hypertension, and
      cancer. Therefore, a rapid and reliable detection and quantification method for
      crAssphage is essential for studying its molecular epidemiology and pathogenicity
      in human diseases. The primers-probes set for the quantitative real-time PCR
      assay was designed based on the DNA polymerase gene (ORF00018) of crAssphage. The
      sensitivity and specificity, as well as comparison testing with the conventional
      PCR and sequencing were evaluated. The assay could specifically detect
      crAssphage, and no cross-reactions with other gut microbes were observed. The
      detection limit was 15.6 copies/MUL of clinical samples (46.8 copies/reaction).
      When using clinical samples, the assay showed higher ability to detect samples
      with low viral DNA copies and had an agreement of 93.33% when compared with the
      conventional PCR amplification and sequencing. The established real-time PCR
      assay is a sensitive, specific, and repeatable method for quantitatively
      detecting crAssphage, and thus is a very useful tool for investigating the
      molecular epidemiology, dynamics, and pathogenicity of crAssphage in human
      diseases.

PMID- 29044636
TI  - An inverse association between serum resistin levels and n-3 polyunsaturated
      fatty acids intake was strongest in the SNP-420 G/G genotype in the Japanese
      cohort: The Toon Genome Study.
AB  - OBJECTIVE: Resistin is secreted by monocytes/macrophages and is associated with
      insulin resistance, inflammation and cardiovascular diseases. In the Japanese
      cohort, serum resistin is tightly associated with a single-nucleotide
      polymorphism (SNP) at -420 (rs1862513) in the promoter region of the human
      resistin gene. However, interactions between SNP-420 and environmental factors
      remain to be elucidated. The aim of this study was to investigate the association
      between serum resistin levels and nutrient intake, and the effect of SNP-420 on
      this association. DESIGN, PARTICIPANTS AND MEASUREMENTS: The Toon Genome Study is
      a cohort study of Japanese community-dwelling subjects. A total of 1981
      participants were cross-sectionally analysed. Each nutrient intake was assessed
      using the semiquantitative food frequency questionnaire and categorized into the
      quartiles (Q1-Q4). Serum resistin was measured by ELISA. RESULTS: Serum resistin
      tended to be inversely associated with fish intake and positively associated with
      meat intake after adjustment for age, sex, BMI and energy intake. Serum resistin
      was inversely associated with n-3 polyunsaturated fatty acids (PUFA) intake after
      adjustment for age, sex, BMI and energy intake (Q1 12.5, Q2 12.5, Q3 12.2, Q4
      11.5 ng/mL; P for trend = .007). This inverse association was strongest in the
      G/G genotype of SNP-420, followed by C/G and C/C (G/G, Q1 18.9, Q2 19.5, Q3 18.4,
      Q4 14.5 ng/mL, P = .001; C/G, 14.4, 13.3, 13.1, 12.9, P = .015; C/C, 9.5, 9.5,
      9.2, 8.8, P = .020; P for interaction = .004). CONCLUSIONS: The inverse
      association between serum resistin and n-3 PUFA intake was strongest in SNP-420
      G/G genotype in the Japanese cohort.

PMID- 29044637
TI  - The modeled cost-effectiveness of family-based and adolescent-focused treatment
      for anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa (AN) is a prevalent, serious mental disorder. We
      aimed to evaluate the cost-effectiveness of family-based treatment (FBT) compared
      to adolescent-focused individual therapy (AFT) or no intervention within the
      Australian healthcare system. METHOD: A Markov model was developed to estimate
      the cost and disability-adjusted life-year (DALY) averted of FBT relative to
      comparators over 6 years from the health system perspective. The target
      population was 11-18 year olds with AN of relatively short duration. Uncertainty
      and sensitivity analyses were conducted to test model assumptions. Results are
      reported as incremental cost-effectiveness ratios (ICER) in 2013 Australian
      dollars per DALY averted. RESULTS: FBT was less costly than AFT. Relative to no
      intervention, the mean ICER of FBT and AFT was $5,089 (95% uncertainty interval
      (UI): dominant to $16,659) and $51,897 ($21,591 to $1,712,491) per DALY averted.
      FBT and AFT are 100% and 45% likely to be cost-effective, respectively, at a
      threshold of AUD$50,000 per DALY averted. Sensitivity analyses indicated that
      excluding hospital costs led to increases in the ICERs but the conclusion of the
      study did not change. CONCLUSION: FBT is the most cost-effective among treatment
      arms, whereas AFT was not cost-effective compared to no intervention. Further
      research is required to verify this result.

PMID- 29044638
TI  - Impact of melatonin supplementation in the rat spermatogenesis subjected to
      forced swimming exercise.
AB  - Oxygen consumption increases many times during exercise, which can increase
      reactive oxygen species. It negatively affects fertility in male athletes.
      Melatonin is exerting a regulatory role at different levels of the hypothalamic
      pituitary-gonadal axis. However, there is no evidence that the protective effects
      of melatonin persist after long duration exercise on the spermatogenesis.
      Therefore, this study was conducted to examine the impacts of melatonin on the
      testis following the administration of swimming exercise. Rats were separated
      into five different groups, including Control, sham M: received the solvent of
      melatonin, M: received melatonin, S: the exercise protocol, MS: received
      melatonin and the exercise protocol. After 8 weeks, animals were scarified and
      antioxidant enzymes levels of testes, spermatogenic cells apoptosis and sperm
      quality were measured. Swimming decreased all parameters of spermatozoa.
      Nevertheless, melatonin could significantly improve the progressive motility of
      spermatozoa in MS rats. Swimming caused an increased apoptosis of S group and
      decreased all antioxidant enzymes. Melatonin could drastically reduce apoptosis
      and increased these enzymes. Therefore, melatonin seems to induce the production
      of antioxidant enzymes of testicular tissues and diminish the extent of apoptotic
      changes caused by forced exercise on the testis, which can, in turn, ameliorate
      the sperm parameters.

PMID- 29044639
TI  - Inflammatory pathology markers (activated microglia and reactive astrocytes) in
      early and late onset Alzheimer disease: a post mortem study.
AB  - AIMS: The association between the pathological features of AD and dementia is
      stronger in younger old persons than in older old persons suggesting that
      additional factors are involved in the clinical expression of dementia in the
      oldest old. Cumulative data suggests that neuroinflammation plays a prominent
      role in Alzheimer's disease (AD) and different studies reported an age-associated
      dysregulation of the neuroimmune system. Consequently, we sought to characterize
      the pattern of microglial cell activation and astrogliosis in brain post mortem
      tissue of pathologically confirmed cases of early and late onset AD (EOAD and
      LOAD) and determine their relation to age. METHODS: Immunohistochemistry (CD68
      and glial fibrillary acidic protein) with morphometric analysis of astroglial
      profiles in 36 cases of AD and 28 similarly aged controls. RESULTS: Both EOAD and
      LOAD groups had higher microglial scores in CA1, entorhinal and temporal
      cortices, and higher astroglial response in CA1, dentate gyrus, entorhinal and
      temporal cortices, compared to aged matched controls. Additionally, EOAD had
      higher microglial scores in subiculum, entorhinal and temporal subcortical white
      matter, and LOAD higher astrogliosis in CA2 region. CONCLUSIONS: Overall, we
      found that the neuroinflammatory pathological markers in late stage AD human
      tissue to have a similar pattern in both EOAD and LOAD, though the severity of
      the pathological markers in the younger group was higher. Understanding the age
      effect in AD will be important when testing modifying agents that act on the
      neuroinflammation.

PMID- 29044640
TI  - A step-down protocol for omalizumab treatment in oral corticosteroid-dependent
      allergic asthma patients.
AB  - AIMS: There are no specific criteria for a step-down or withdrawal dose of
      omalizumab (OMA). Our purpose was to evaluate the viability of a protocol for
      OMAlizumab DOse REduction (the OMADORE study) in severe allergic asthma (SAA).
      METHODS: The study population included 35 SAA patients treated during a minimum
      period of 1 year with oral corticosteroids (OC) equivalent to a mean daily dose
      of 4 mg of methyl-prednisolone. To qualify for the protocol, the patients had to
      have received treatment with OMA for at least one and a half years, OC dose had
      to have reached the lowest tolerated dose and spirometry had to be greater than
      or equal to that at entry. The interventions were (a) OMA dose was reduced by
      half; (b) if patients were clinically stable after 6 months, the dose was halved
      again; (c) if repeated OC boosters were needed and/or spirometry worsened by more
      than 10%, OMA dose was raised to the previous figure until stabilization.
      RESULTS: Mean age was 52.5 (17) years, median monthly OC dose was 120 (IQR: 225)
      mg. Pulmonary function: FVC: 79.7 (20.2)%; FEV1 : 64.8 (21.7)%; FEV1 / FVC:
      61.7(13.8)%. OMA could be withdrawn in 34.3% of the patients; 22.9% tolerated a
      reduction, and in 42.9% the dose could not be modified. Follow-up time after
      reduction or withdrawal ranged from 12 to 30 months. There were no severe
      exacerbations requiring emergency assistance or admission. CONCLUSIONS: The
      OMADORE study found that in more than 50% of SAA patients on OC, OMA dose can be
      safely reduced or withdrawn based on a progressive dose reduction protocol.

PMID- 29044641
TI  - Qualitative and Semiquantitative Elastography for the Diagnosis of Intermediate
      Suspicious Thyroid Nodules Based on the 2015 American Thyroid Association
      Guidelines.
AB  - OBJECTIVES: To evaluate qualitative and semiquantitative elastography for the
      diagnosis of intermediate suspicious thyroid nodules based on the 2015 American
      Thyroid Association (ATA) guidelines. METHODS: Through a retrospective search of
      our institutional database, 746 solid thyroid nodules found on grayscale
      ultrasonography, strain elastography, and ultrasound-guided fine-needle
      aspiration between June and November 2009 were collected. Among them, 80 nodules
      from 80 patients with an intermediate suspicion of malignancy based on the 2015
      ATA guidelines that were 10 mm or larger were recruited as the final study
      nodules. Elastographic findings were categorized according to the criteria of
      Rago et al (J Clin Endocrinol Metab 2007; 92:2917-2922) and Asteria et al
      (Thyroid 2008; 18:523-531), and strain ratio values were calculated and recorded.
      The independent 2-sample t test and chi2 test (or Fisher exact test) were used to
      evaluate differences in clinical parameters between benign and malignant thyroid
      nodules. All variables were compared by univariate and multivariate logistic
      regression analyses, and odds ratios with 95% confidence intervals were
      calculated. RESULTS: Of the 80 nodules, 6 (7.5%) were malignant, and 74 (92.5%)
      were benign. No significant differences were observed in age, sex, nodule size,
      elasticity score, and strain ratio between benign and malignant nodules. No
      variables significantly predicted thyroid malignancy on the univariate analysis.
      On the multivariate logistic regression analysis, there were no independent
      variables associated with thyroid malignancy, including the elasticity score and
      strain ratio (all P > .05). CONCLUSIONS: Elastographic analysis using the
      elasticity score and strain ratio has limited ability to characterize the
      benignity or malignancy of thyroid nodules with an intermediate suspicion of
      malignancy based on the 2015 ATA guidelines.

PMID- 29044642
TI  - Assessment of public health core competencies in prelicensure baccalaureate
      nursing students.
AB  - OBJECTIVE: The purpose of this study was to assess the use of the Public Health
      Foundation's (Public Health Foundation [PHF], ) Competency Assessment for Tier 1
      Public Health Professionals to examine prelicensure baccalaureate nursing
      students' self-reported levels of competence in public health before and after
      completing community health nursing courses. DESIGN: Prelicensure baccalaureate
      nursing students enrolled in community health nursing courses completed a pre and
      postcourse Competency Assessment for Tier 1 Public Health Professionals survey.
      The survey results were analyzed using nonparametric tests to determine whether
      there were significant differences in pre and postsurvey scores for the eight
      domains of public health core competencies, and for an overall competency score.
      RESULTS: Significant differences were found in the pre and postaggregate mean
      scores for each of the eight domains of public health core competency, and the
      overall mean public health competency score. Chi-square testing of pre and
      postcourse competency found significant difference in the proportion of students
      who met criteria for self-reported competence in each of the eight domains and
      overall public health competence. CONCLUSION: The Competency Assessment for Tier
      1 Public Health Professionals can assist baccalaureate nursing faculty with
      assessing precourse learning needs, and postcourse evaluation of self-reported
      competence in public health.

PMID- 29044643
TI  - Fidaxomicin versus Vancomycin as a First-Line Treatment for Clostridium difficile
      Associated Diarrhea in Specific Patient Populations: A Pharmacoeconomic
      Evaluation.
AB  - OBJECTIVES: The reduction in recurrent Clostridium difficile-associated diarrhea
      (CDAD) with fidaxomicin therapy may reduce hospital readmissions and lead to
      lower overall CDAD costs. However, studies assessing the cost-effectiveness of
      fidaxomicin as first-line therapy from the U.S. hospital perspective are lacking.
      This study evaluated the costs associated with utilizing fidaxomicin or
      vancomycin as a first-line therapy for CDAD in specific patient populations from
      a U.S. hospital perspective. METHODS: A decision-analytic model was developed to
      estimate total costs (hospitalization and drug costs) associated with using
      fidaxomicin or vancomycin as first-line therapy for a first episode and up to two
      recurrences of CDAD in five patient populations: general population, elderly,
      patients receiving concomitant antibiotics, and patients with renal impairment or
      cancer. RESULTS: The total cost of CDAD treatment using fidaxomicin first line in
      the general population was $14,442 per patient versus $14,179 per patient with
      vancomycin first line. In subgroup analyses, fidaxomicin use resulted in total
      hospital cost savings of $616 per patient in patients with cancer and $312 in
      patients with concomitant antibiotic use; vancomycin use was associated with
      total hospital cost savings of $243 per patient in the elderly and $371 in
      patients with renal impairment. CONCLUSIONS: Fidaxomicin as first-line CDAD
      therapy is associated with similar total costs as compounded vancomycin oral
      solution in the general population. In elderly and renally impaired patients,
      slight increases in hospital cost were observed with fidaxomicin therapy, and in
      patients with cancer or concomitant antibiotic use, hospital cost savings were
      observed.

PMID- 29044645
TI  - Erratum.

PMID- 29044644
TI  - Hermansky-Pudlak syndrome: Report of two patients with updated genetic
      classification and management recommendations.
AB  - Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder caused by
      mutations in one of nine genes involved in the packaging and formation of
      specialized lysosomes, including melanosomes and platelet-dense granules. The
      cardinal features are pigmentary dilution, bleeding diathesis, and accumulation
      of ceroid-like material in reticuloendothelial cells. Pulmonary fibrosis induced
      by tissue damage is seen in the most severe forms, and one subtype is
      characterized by immunodeficiency. We describe two patients with HPS type 1 and
      review the updated gene-based classification, clinical features, and
      recommendations for evaluation and follow-up.

PMID- 29044646
TI  - Topographical anatomy of the intestines during in utero physiological herniation.
AB  - Because most malrotations of the small intestine are thought to occur during
      repackaging, the location of the intestine should vary less during physiological
      herniation than afterward. Examination of serial sagittal sections of 27 embryos
      and fetuses (gestational age 6-9 weeks; crown-rump length 15-45 mm) during
      herniation showed that the jejunum and ascending colon passed through a small
      opening of the hernia sac at the levels of the stomach and pancreas in 16
      specimens. Below the pancreas, a definite mesentery extended between the
      ascending and descending colon in the abdominal cavity. In the other 11
      specimens, the descending colon passed through an opening of normal size and ran
      posteriorly along the urinary bladder, so the entire ilium, ascending colon, and
      transverse colon entered the sac. In these specimens, the duodenojejunal junction
      was usually situated in a window of the mesentery of the colon (internal
      herniation). The descending colon was observed at an outside location more
      frequently in earlier specimens. In contrast to our working hypothesis, the
      locations of the intestine were abnormal in 40.7% (11/27) of samples. In
      addition, no abnormal colon was observed in any of the seven specimens after
      repackaging. An outside location of the descending colon was not directly
      associated with malrotation because recovery was likely. However, the delayed
      development of the inferior mesenteric arterial branches could cause failure,
      including death in utero, during or after the repackaging associated with
      physiological herniation. Clin. Anat. 31:583-592, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29044648
TI  - Procedural endpoints of catheter ablation for atrial fibrillation: Arrhythmia
      termination or end of CFAE ablation?

PMID- 29044650
TI  - Knowledge translation in occupational therapy.

PMID- 29044647
TI  - Epilepsy and astrocyte energy metabolism.
AB  - Epilepsy is a complex neurological syndrome characterized by neuronal
      hyperexcitability and sudden, synchronized electrical discharges that can
      manifest as seizures. It is now increasingly recognized that impaired astrocyte
      function and energy homeostasis play key roles in the pathogenesis of epilepsy.
      Excessive neuronal discharges can only happen, if adequate energy sources are
      made available to neurons. Conversely, energy depletion during seizures is an
      endogenous mechanism of seizure termination. Astrocytes control neuronal energy
      homeostasis through neurometabolic coupling. In this review, we will discuss how
      astrocyte dysfunction in epilepsy leads to distortion of key metabolic and
      biochemical mechanisms. Dysfunctional glutamate metabolism in astrocytes can
      directly contribute to neuronal hyperexcitability. Closure of astrocyte
      intercellular gap junction coupling as observed early during epileptogenesis
      limits activity-dependent trafficking of energy metabolites, but also impairs
      clearance of the extracellular space from accumulation of K+ and glutamate.
      Dysfunctional astrocytes also increase the metabolism of adenosine, a metabolic
      product of ATP degradation that broadly inhibits energy-consuming processes as an
      evolutionary adaptation to conserve energy. Due to the critical role of
      astroglial energy homeostasis in the control of neuronal excitability, metabolic
      therapeutic approaches that prevent the utilization of glucose might represent a
      potent antiepileptic strategy. In particular, high fat low carbohydrate
      "ketogenic diets" as well as inhibitors of glycolysis and lactate metabolism are
      of growing interest for the therapy of epilepsy.

PMID- 29044651
TI  - Weak evidence supports intensive, task-oriented, early intervention with parent
      support for infants with, or at high risk of, cerebral palsy.

PMID- 29044652
TI  - The impact of accreditation on medical schools' processes.
AB  - OBJECTIVES: Increased emphasis is being placed worldwide on accreditation of
      undergraduate medical education programmes, and costs of participation in
      accreditation continue to rise. The primary purposes of accreditation are to
      ensure the quality of medical education and to promote quality improvement.
      Student performance data as indicators of the impact of accreditation have
      important limitations. The purpose of this study was to evaluate the impact of
      accreditation using an innovative marker: the processes implemented at medical
      schools as a result of accreditation. This conceptual model suggests that
      accreditation drives medical schools to implement and strengthen processes that
      support quality in medical education. METHODS: In this qualitative study,
      conducted in 2015-2016, interviews and focus group discussions with deans,
      undergraduate medical education deans and faculty leaders at 13 of the 17
      Canadian medical schools were used to elicit perspectives about processes
      influenced by accreditation; the method of constant comparative analysis
      associated with grounded theory was used to generate themes of processes.
      Perceived negative consequences of accreditation on medical education programmes
      were also explored. RESULTS: Nine themes representing processes reported as
      resulting from accreditation were identified. These processes related to: (i)
      governance, (ii) data collection and analysis, (iii) monitoring, (iv)
      documentation, (v) creation and revision of policies and procedures, (vi)
      continuous quality improvement, (vii) faculty members' engagement, (viii)
      academic accountability and (ix) curriculum reforms. Themes representing negative
      consequences of accreditation included (i) costs, (ii) staff and faculty members'
      morale and feelings, (iii) school reputation and (iv) standards. The identified
      processes, given their nature, appear likely to be associated with improvement of
      quality in medical education. These results help justify the costs associated
      with accreditation. CONCLUSIONS: This study uses an innovative marker, medical
      schools' processes, to evaluate the impact of accreditation. Results provide
      evidence that accreditation-related activities steer medical education programmes
      towards establishment of processes likely to be associated with improved quality
      in medical education.

PMID- 29044653
TI  - Morphological changes of the optic lobe from late embryonic to adult stages in
      oval squids Sepioteuthis lessoniana.
AB  - The optic lobe is the largest brain area within the central nervous system of
      cephalopods and it plays important roles in the processing of visual information,
      the regulation of body patterning, and locomotive behavior. The oval squid
      Sepioteuthis lessoniana has relatively large optic lobes that are responsible for
      visual communication via dynamic body patterning. It has been observed that the
      visual behaviors of oval squids change as the animals mature, yet little is known
      about how the structure of the optic lobes changes during development. The aim of
      the present study was to characterize the ontogenetic changes in neural
      organization of the optic lobes of S. lessoniana from late embryonic stage to
      adulthood. Magnetic resonance imaging and micro-CT scans were acquired to
      reconstruct the 3D-structure of the optic lobes and examine the external
      morphology at different developmental stages. In addition, optic lobe slices with
      nuclear staining were used to reveal changes in the internal morphology
      throughout development. As oval squids mature, the proportion of the brain making
      up the optic lobes increases continuously, and the optic lobes appear to have a
      prominent dent on the ventrolateral side. Inside the optic lobe, the cortex and
      the medulla expand steadily from the late embryonic stage to adulthood, but the
      cell islands in the tangential zone of the optic lobe decrease continuously in
      parallel. Interestingly, the size of the nuclei of cells within the medulla of
      the optic lobe increases throughout development. These findings suggest that the
      optic lobe undergoes continuous external morphological change and internal neural
      reorganization throughout the oval squid's development. These morphological
      changes in the optic lobe are likely to be responsible for changes in the
      visuomotor behavior of oval squids from hatching to adulthood.

PMID- 29044654
TI  - Animal models of neuroinflammation secondary to acute insults originated outside
      the brain.
AB  - The term "neuroinflammation" has been widely used to describe a series of acute
      or chronic conditions that cause inflammation in the central nervous system
      (CNS). Neurological damage can be a consequence of direct local injury or,
      secondary, of systemic or even distant inflammatory processes. In this respect,
      animal models have been developed to better understand the pathophysiology and,
      possibly, to evaluate more effective methods of treatment for these disorders.
      Animal models that promote alterations in blood-brain barrier permeability-the
      activation of microglia or astrocytes, modifications in neuropeptide expression,
      oxidative stress, increased apoptosis, release of inflammatory mediators,
      leukocyte infiltration, and brain edema-are likely to involve neuroinflammation
      and therefore can serve as useful models for human inflammatory CNS injury. This
      review describes the major animal models of neuroinflammation triggered by
      systemic or distant inflammatory processes. We will focus on animal models of
      acute neurologic damage; experimental models that lead to chronic
      neuroinflammation will not be addressed here.

PMID- 29044656
TI  - Abstracts of the 26th Annual Meeting of the German Transplantation Society, Bonn,
      Germany, 25-28 October 2017.

PMID- 29044655
TI  - Secondary skin involvement by systemic de novo CD5-positive diffuse large B-cell
      lymphoma.

PMID- 29044657
TI  - Abstracts from the 2017 Meeting of the American Association of Veterinary
      Anatomists, held June 29-July 1, College of Veterinary Medicine, Auburn
      University, Auburn, AL, USA.

PMID- 29044658
TI  - Gills of the medaka (Oryzias latipes): A scanning electron microscopy study.
AB  - The general morphology and surface ultrastructure of the gills of adult and
      larvae medaka (Oryzias latipes) were studied in freshwater and seawater using
      scanning electron microscopy. The gills of all examined fish were structurally
      similar to those of other teleosts and consisted of four pairs of arches
      supporting (i) filaments bearing lamellae and (ii) rakers containing taste buds.
      Three cell types, specifically pavement cells, mitochondria-rich cells (MRCs),
      and mucous cells, constituted the surface layer of the gill epithelium. Several
      distinctive characteristics of medaka gills were noted, including the presence of
      regularly distributed outgrowth on the lamellae, enlarged filament tips, the
      absence of microridges in most pavement cells in the filament and lamellae and
      the presence of MRCs in the arch at the filament base. A rapid mode of
      development was recorded in the gills of larval fish. At hatching, the larvae
      already had four arches with rudimentary filaments, rakers, and taste buds. The
      rudimentary lamellae appeared within 2 days after hatching. These results suggest
      the early involvement of larval gills in respiratory and osmoregulation
      activities. The responses of the macrostructures and microstructures of gills to
      seawater acclimation were similar in larvae and adult fish and included
      modification of the apical surface of MRCs, confirming the importance of these
      cells in osmoregulation. The potential roles of these peculiarities of the
      macrostructures and microstructures of medaka gills in the major functions of
      this organ, such as respiration and osmoregulation, are discussed.

PMID- 29044659
TI  - The early signs of reading difficulties at school can start with foetal growth
      restriction.

PMID- 29044660
TI  - Real-world treatment patterns and outcomes among metastatic cutaneous melanoma
      patients treated with ipilimumab.
AB  - BACKGROUND: There is a scarcity of real-world data on treatment patterns and
      outcomes among advanced melanoma patients treated with immunotherapies including
      ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE: To evaluate
      ipilimumab and postipilimumab treatment patterns and outcomes among patients with
      advanced melanoma in Australia, Germany, Italy and Spain, following regulatory
      approval. METHODS: Retrospective multicentre, multinational, observational chart
      review study. Data were extracted from the start of ipilimumab therapy until the
      end of at least 40 weeks of follow-up, or death. RESULTS: Data from 371 patients
      (Australia, 103; Germany, 152; Italy, 76; Spain, 40) were analysed. Mean age was
      65 years; 62% were male. Eastern Cooperative Oncology Group performance status
      (ECOG PS) was 0 or 1 for 94%. In 67%, ipilimumab was initially received as second
      line or later therapy. Patients received on average 3.4 ipilimumab doses. The
      ipilimumab-refractory cohort comprised of 226 patients. Of these, 17% in
      Australia, 47% in Germany, 29% in Italy and 14% in Spain received another
      antimelanoma treatment after ipilimumab including chemotherapy in 26% and
      BRAF/other kinase inhibitors in 11%. Ipilimumab-refractory patients who received
      postipilimumab treatment showed a 40% reduced hazard of dying than those not
      receiving treatment after ipilimumab (HR 0.60; 95% CI 0.43-0.83), after
      adjustment for potential confounders. CONCLUSION: During the time observed,
      ipilimumab was mainly used as second-line or later therapy. A significant
      proportion of patients received postipilimumab therapy, most of which was
      chemotherapy. Nevertheless, overall survival following progression on ipilimumab
      treatment remained poor, highlighting the need for research to develop more
      effective end-of-life treatment options.

PMID- 29044661
TI  - The Role of Sexual Communication in Couples' Sexual Outcomes: A Dyadic Path
      Analysis.
AB  - In a study of 142 couples, we gathered survey data to show how sexual
      communication influences sexual and relationship satisfaction as well as sexual
      and orgasm frequency. In two dyadic data path analyses, we observed the
      significant paths of influence that sexual communication has on sexual and
      relationship satisfaction, as well as sexual and orgasm frequency. Our findings
      revealed greater amounts of sexual communication were associated with increased
      orgasm frequency in women and greater relationship and sexual satisfaction in
      both sexes. We also observed important differences in the associations of sexual
      communication and general communication on satisfaction levels. With these
      analyses, we expand the current literature to broaden our understanding of the
      role that sexual communication plays in committed relationships.

PMID- 29044663
TI  - Forensic source attribution for toluene in environmental samples.
AB  - The formation of toluene by microbiological processes can confound environmental
      investigations relating to petroleum releases. This is because toluene is a
      constituent of petroleum and can move readily within wetland environments, and
      analysis for toluene in relation to a petroleum release can lead to incorrect
      assignment of detected biogenic toluene as related to the release. No legally
      defensible method of distinguishing biogenic and petrogenic origins of detectible
      concentrations of toluene have been demonstrated to date. Using example
      petrogenic samples and samples of peat from 2 wetland environments, a poor bog
      and a poor fen, the present study demonstrates the use of an established ASTM
      International analytical methodology that was originally designed for arson
      analysis for the determination of the origin of toluene. Environmental forensic
      data-interpretation methods such as chromatogram inspection and diagnostic ratios
      are shown to be capable of readily distinguishing biogenic and petrogenic origins
      of toluene. Environ Toxicol Chem 2018;37:729-737. (c) 2017 SETAC.

PMID- 29044662
TI  - The terpene synthase gene family in Gossypium hirsutum harbors a linalool
      synthase GhTPS12 implicated in direct defence responses against herbivores.
AB  - Herbivore-induced terpenes have been reported to function as ecological signals
      in plant-insect interactions. Here, we showed that insect-induced cotton volatile
      blends contained 16 terpenoid compounds with a relatively high level of linalool.
      The high diversity of terpene production is derived from a large terpene synthase
      (TPS) gene family. The TPS gene family of Gossypium hirsutum and Gossypium
      raimondii consist of 46 and 41 members, respectively. Twelve TPS genes (GhTPS4
      15) could be isolated, and protein expression in Escherichia coli revealed
      catalytic activity for eight GhTPS. The upregulation of the majority of these
      eight genes additionally supports the function of these genes in herbivore
      induced volatile biosynthesis. Furthermore, transgenic Nicotiana tabacum plants
      overexpressing GhTPS12 were generated, which produced relatively large amounts of
      (3S)-linalool. In choice tests, female adults of Helicoverpa armigera laid fewer
      eggs on transgenic plants compared with non-transformed controls. Meanwhile,
      Myzus persicae preferred feeding on wild-type leaves over leaves of transgenic
      plants. Our findings demonstrate that transcript accumulation of multiple TPS
      genes is mainly responsible for the production and diversity of herbivore-induced
      volatile terpenes in cotton. Also, these genes might play roles in plant defence,
      in particular, direct defence responses against herbivores.

PMID- 29044664
TI  - A new technique of surgical planning for anterior cruciate ligament
      reconstruction: Feasibility Assessment of Shear Wave Elastography to Tendon of
      Semitendinosus Muscle.
AB  - There is currently no method to quantify the quality of the harvested graft
      before anterior cruciate ligament (ACL) reconstruction. The purpose of this study
      was to explore a method for measuring stiffness of the normal tendon of the
      semitendinosus muscle using shear wave elastography (SWE). Our investigation
      comprised two steps. First, we determined orientation of the semitendinosus
      tendon fibers in 20 lower legs of embalmed cadavers. Second, we investigated the
      feasibility of quantifying stiffness of the normal semitendinosus tendon by SWE
      in 24 subjects (48 legs: 24 male and 24 female subjects) in vivo. Measured values
      were compared between male and female subjects. The point at the intersection of
      the semitendinosus tendon with the axial section through the center of the
      patella mostly was the middle of the semitendinosus tendon in the cadavers. The
      SWE modulus in all of the subjects could be measured on this point in vivo. The
      SWE modulus of males and females were 474.0 +/- 71.9 kPa and 396.9 +/- 104.5 kPa,
      respectively. The SWE modulus of males was significantly larger than that of
      females (P < 0.01). This study demonstrates that stiffness of the tendon of the
      semitendinosus muscle can be measured by SWE. It also shows that tendon of the
      semitendinosus muscle in males is stiffer than in females. Clin. Anat. 31:404
      408, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29044666
TI  - Child Vision Research Society conference report.

PMID- 29044667
TI  - Blue-light filtering ophthalmic lenses: to prescribe, or not to prescribe?

PMID- 29044668
TI  - Winners in the 2016 Naylor Prize competition.

PMID- 29044669
TI  - The advantages of intermediate-tier, inter-optometric referral of low risk
      pigmented lesions.
AB  - PURPOSE: Pigmented ocular lesions are commonly encountered by eye-care
      professionals, and range from benign to sight or life-threatening. After
      identifying a lesion, the primary care professional must establish the likely
      diagnosis and decide either to reassure, to monitor or to refer. The increasing
      use of ocular imaging technologies has contributed to an increase in the
      detection rate of pigmented lesions and a higher number of referrals, which may
      challenge existing pathways of health-care delivery. Specialist services may be
      over-burdened by referring all patients with pigmented lesions for an opinion,
      while inter-optometric referrals are underutilised. The aim of this study was to
      describe the referral patterns of pigmented lesions to an optometry led
      intermediate-tier collaborative care clinic. METHODS: We performed a
      retrospective review of patient records using the list of patients examined at
      Centre for Eye Health (CFEH) for an initial or follow up pigmented lesion
      assessment between the 1/7/2013 and the 30/6/2016. Analysis was performed on:
      patient demographic characteristics, the referrer's tentative diagnosis, CFEH
      diagnosis and recommended management plan. RESULTS: Across 182 patient records,
      the primary lesion prompting referral was usually located in the posterior
      segment: choroidal naevus (105/182, 58%), congenital hypertrophy of the retinal
      pigment epithelium (CHRPE; 11/182, 6%), chorioretinal scarring (10/182, 5%) or
      not specified (52/182, 29%). Referrals described a specific request for ocular
      imaging in 25 instances (14%). The number of cases with a non-specific diagnosis
      was reduced after intermediate-tier care assessment (from 29% to 10%), while the
      number of diagnoses with less common conditions rose (from 2% to 21%). There was
      a 2% false positive referral rate to intermediate-tier care and a first visit
      discharge rate of 35%. A minority required on-referral to an ophthalmologist
      (22/182, 12%), either for unrelated incidental ocular findings, or suspicious
      choroidal naevi. Conditions most amenable to optometric follow up included: 1)
      chorioretinal scarring, 2) choroidal naevus, and 3) CHRPE. CONCLUSIONS:
      Intermediate-tier optometric eye-care in pigmented lesions (following
      opportunistic primary care screening) has the potential to reduce the number of
      cases with non-specific diagnoses and to increase those with less common
      diagnoses. The majority of cases seen under this intermediate-tier model required
      only ongoing optometric surveillance.

PMID- 29044670
TI  - The effect of blue-light blocking spectacle lenses on visual performance, macular
      health and the sleep-wake cycle: a systematic review of the literature.
AB  - PURPOSE: Blue-blocking (BB) spectacle lenses, which attenuate short-wavelength
      light, are being marketed to alleviate eyestrain and discomfort when using
      digital devices, improve sleep quality and potentially confer protection from
      retinal phototoxicity. The aim of this review was to investigate the relative
      benefits and potential harms of these lenses. METHODS: We included randomised
      controlled trials (RCTs), recruiting adults from the general population, which
      investigated the effect of BB spectacle lenses on visual performance, symptoms of
      eyestrain or eye fatigue, changes to macular integrity and subjective sleep
      quality. We searched MEDLINE, EMBASE, the Cochrane Library and clinical trial
      registers, until 30 April 2017. Risk of bias was assessed using the Cochrane
      tool. RESULTS: Three studies (with 136 participants) met our inclusion criteria;
      these had limitations in study design and/or implementation. One study compared
      the effect of BB lenses with clear lenses on contrast sensitivity (CS) and colour
      vision (CV) using a pseudo-RCT crossover design; there was no observed difference
      between lens types (log CS; Mean Difference (MD) = -0.01 [-0.03, 0.01], CV total
      error score on 100-hue; MD = 1.30 [-7.84, 10.44]). Another study measured
      critical fusion frequency (CFF), as a proxy for eye fatigue, on wearers of low
      and high BB lenses, pre- and post- a two-hour computer task. There was no
      observed difference between low BB and standard lens groups, but there was a less
      negative change in CFF between the high and low BB groups (MD = 1.81 [0.57,
      3.05]). Both studies compared eyestrain symptoms with Likert scales. There was no
      evidence of inter-group differences for either low BB (MD = 0.00 [-0.22, 0.22])
      or high BB lenses (MD = -0.05 [-0.31, 0.21]), nor evidence of a difference in the
      proportion of participants showing an improvement in symptoms of eyestrain or eye
      fatigue. One study reported a small improvement in sleep quality in people with
      self-reported insomnia after wearing high compared to low-BB lenses (MD = 0.80
      [0.17, 1.43]) using a 10-point Likert scale. A study involving normal
      participants found no observed difference in sleep quality. We found no studies
      investigating effects on macular structure or function. CONCLUSIONS: We find a
      lack of high quality evidence to support using BB spectacle lenses for the
      general population to improve visual performance or sleep quality, alleviate eye
      fatigue or conserve macular health.

PMID- 29044671
TI  - Coloured filters show gender differences and poor repeatability.

PMID- 29044672
TI  - Virtual Issue Editorial: Presbyopia - grappling with an age-old problem.

PMID- 29044673
TI  - Modeling the effects of thiamethoxam on Midwestern farm ponds and emergent
      wetlands.
AB  - Potential toxic effects of thiamethoxam on nontarget organisms and the community
      structure of a generic Midwestern farm pond and emergent wetland were assessed
      using 2 versions of the comprehensive aquatic system model: CASMGFP , a generic
      farm pond model, and CASMGWL , a generic wetland model. The CASMGFP and CASMGWL
      are integrated bioenergetics-based and habitat quality models that describe the
      daily biomass values of selected producer and consumer populations representative
      of generalized Midwestern farm ponds and emergent wetlands. The CASMGFP
      demonstrated the ability to reproduce values of population biomass reported for
      Midwestern (and other) pond ecosystems; the CASMGWL provided a similar modeling
      capability for Midwestern emergent wetlands. Lethal and sublethal effects of
      thiamethoxam were modeled as extrapolations of laboratory toxicity assays using
      the CASMGFP and the CASMGWL . Time series of daily environmental concentrations
      of thiamethoxam constructed for 6 regional pesticide applications across the
      United States failed to produce any calculated impacts on modeled population
      biomass or changes in community structure of modeled trophic guilds in the
      CASMGFP or the CASMGWL . However, evaluation of systematically increased daily
      concentrations demonstrated the ability of both models to simulate direct and
      indirect toxic effects of this pesticide. The present model study suggests that
      process-based food web/ecosystem models can be used to characterize the potential
      ecological effects of thiamethoxam on generalized farm pond and emergent wetland
      ecosystems. Environ Toxicol Chem 2018;37:738-754. (c) 2017 SETAC.

PMID- 29044674
TI  - Haem is associated with thrombosis in neonates and infants undergoing cardiac
      surgery for congenital heart disease.
AB  - BACKGROUND: Haem levels are associated with thrombosis in a variety of diseases,
      as well as being a contributing cause of thrombotic events in animal models.
      MATERIALS AND METHODS: We retrospectively analyzed samples from 39 children who
      underwent cardiac surgery with cardiopulmonary bypass, including 15 children who
      developed a postoperative thrombosis and 24 controls. RESULTS: Patients who
      developed thrombosis postoperatively had statistically significant higher average
      haem levels over time (presurgery to 12 h postsurgery) compared to patients who
      did not develop thrombosis. CONCLUSION: Higher cell-free total haem levels are
      associated with a higher risk of thrombosis in a paediatric cardiac surgical
      cohort.

PMID- 29044675
TI  - 'Oh my God, I can't handle this!': trainees' emotional responses to complex
      situations.
AB  - CONTEXT: Dealing with emotions is critical for medical trainees' professional
      development. Taking a sociocultural and narrative approach to understanding
      emotions, we studied complex clinical situations as a specific context in which
      emotions are evoked and influenced by the social environment. We sought to
      understand how medical trainees respond to emotions that arise in those
      situations. METHODS: In an international constructivist grounded theory study, 29
      trainees drew two rich pictures of complex clinical situations, one exciting and
      one frustrating. Rich pictures are visual representations that capture
      participants' perceptions about the people, situations and factors that create
      clinical complexity. These pictures were used to guide semi-structured,
      individual interviews. We analysed visual materials and interviews in an
      integrated way, starting with looking at the drawings, doing a 'gallery walk',
      and using the interviews to inform the aesthetic analysis. RESULTS: Participants'
      drawings depicted a range of personal emotions in response to complexity, and
      disclosed unsettling feelings and behaviours that might be considered
      unprofessional. When trainees felt confident, they were actively participating,
      engaged in creative problem-solving strategies, and emphasised their personal
      involvement. When trainees felt the situation was beyond their control, they
      described how they were running away from the situation, hiding themselves behind
      others or distancing themselves from patients or families. CONCLUSIONS: A sense
      of control seems to be a key factor influencing trainees' emotional and
      behavioural responses to complexity. This is problematic, as complex situations
      are by their nature emergent and dynamic, which limits possibilities for control.
      Following a social performative approach to emotions, we should help students
      understand that feeling out of control is an inherent property of participating
      in complex clinical situations, and, by extension, that it is not something they
      will 'grow out of' with expertise.

PMID- 29044676
TI  - World Health Organization-defined eosinophilic disorders: 2017 update on
      diagnosis, risk stratification, and management.
AB  - DISEASE OVERVIEW: The eosinophilias encompass a broad range of nonhematologic
      (secondary or reactive) and hematologic (primary, clonal) disorders with
      potential for end-organ damage. DIAGNOSIS: Hypereosinophilia has generally been
      defined as a peripheral blood eosinophil count greater than 1500/mm3 and may be
      associated with tissue damage. After exclusion of secondary causes of
      eosinophilia, diagnostic evaluation of primary eosinophilias relies on a
      combination of morphologic review of the blood and marrow, standard cytogenetics,
      fluorescent in situ-hybridization, flow immunocytometry, and T-cell clonality
      assessment to detect histopathologic or clonal evidence for an acute or chronic
      myeloid or lymphoproliferative disorder. RISK STRATIFICATION: Disease prognosis
      relies on identifying the subtype of eosinophilia. After evaluation of secondary
      causes of eosinophilia, the 2016 World Health Organization endorses a semi
      molecular classification scheme of disease subtypes which includes the major
      category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of
      PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2," and the "MPN subtype, chronic
      eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant
      hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and
      idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion. RISK
      ADAPTED THERAPY: The goal of therapy is to mitigate eosinophil-mediated organ
      damage. For patients with milder forms of eosinophilia (e.g., < 1500/mm3 )
      without symptoms or signs of organ involvement, a watch and wait approach with
      close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB
      is critical because of the exquisite responsiveness of these diseases to
      imatinib. Corticosteroids are first-line therapy for patients with lymphocyte
      variant hypereosinophilia and HES. Hydroxyurea and interferon-alpha have
      demonstrated efficacy as initial treatment and steroid-refractory cases of HES.
      In addition to hydroxyurea, second line cytotoxic chemotherapy agents and
      hematopoietic cell transplant have been used for aggressive forms of HES and CEL
      with outcomes reported for limited numbers of patients. The use of antibodies
      against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), and
      CD52 (alemtuzumab), as well as other targets on eosinophils remains an active
      area of investigation.

PMID- 29044677
TI  - Sagittal plane walking patterns are related to MRI changes over 18-months in
      people with and without mild-moderate hip osteoarthritis.
AB  - The purpose was to evaluate the association of sagittal plane gait mechanics with
      MRI changes in the hip joint over 18-months. Subjects with and without
      radiographic hip OA (n = 57) underwent MRI at baseline and 18 months for grading
      of cartilage lesions, bone marrow lesions (BML), cysts, and labral tears. 3D gait
      analyses at baseline were used for sagittal plane hip kinematics and kinetics
      during the stance phase. Subjects were classified as progressors or non
      progressors based on increase in any MRI OA parameter. Multivariate ANOVA were
      used for differences in sagittal gait parameters between progressors and non
      progressors at baseline while adjusting for age. Logistic regression was used to
      estimate the probability of being classified as a progressor or non-progressor
      with increasing hip flexion while adjusting for age, BMI, sex, and presence of
      radiographic hip OA. Of the 57, 35 were classified as non-progressors and 22 were
      classified as progressors. At baseline, the progressors walked with 4.5 degrees 
      greater hip flexion during early stance (p = 0.021) and 3.5 degrees  lesser hip
      extension in late stance that was nearly significant (p = 0.059). Walking with
      greater hip flexion at baseline was associated with a greater risk of increase in
      MRI defined structural changes in the hip joint (Odds Ratio = 1.1, p = 0.038).
      Greater hip flexion during walking was associated with a risk of structural
      progression of hip OA. The results may guide future interventions to alter the
      walking patterns and slow structural hip OA progression.(c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1472-1477,
      2018.

PMID- 29044678
TI  - Preliminary investigation of orally administered benazepril in horses with left
      sided valvular regurgitation.
AB  - BACKGROUND: Despite the paucity of data available, orally administered
      angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses
      with valvular regurgitation. OBJECTIVE: Evaluate the echocardiographic and
      hormonal changes in response to oral benazepril in horses with left-sided
      valvular regurgitation. STUDY DESIGN: Prospective, randomised double-blind,
      placebo-controlled trial. METHODS: Horses with mitral valve (MR) and/or aortic
      valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg
      q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before
      drug administration and after 28 days of treatment. Plasma renin activity, serum
      ACE activity, angiotensin II concentration, aldosterone concentration and
      biochemical variables were measured before drug administration and after 7 and 28
      days of treatment. RESULTS: Relative to baseline, horses treated with benazepril
      had statistically significant reduction in left ventricular internal diameter in
      systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm),
      aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic
      annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%)
      compared with horses receiving a placebo. In addition, horses treated with
      benazepril had a significantly greater increase in cardiac output (11.95 L/min;
      1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with
      horses receiving a placebo. Despite profound serum ACE inhibition, renin activity
      and concentrations of angiotensin II and aldosterone were not significantly
      different between treatment groups or among time points. MAIN LIMITATIONS: Very
      small sample size and short treatment period. CONCLUSIONS: Treatment with oral
      benazepril resulted in statistically significant echocardiographic changes that
      might indicate reduced cardiac afterload in horses with left-sided valvular
      regurgitation. Additional studies with a larger sample size will be necessary to
      determine if administration of benazepril is beneficial in horses with valvular
      regurgitation. The Summary is available in Spanish - see Supporting Information.

PMID- 29044679
TI  - Predictors of long-term bladder management in spinal cord injury patients-Upper
      extremity function may matter most.
AB  - INTRODUCTION: Clean intermittent catheterization (CIC) is the gold standard for
      neurogenic bladder management in most patients with spinal cord injury (SCI).
      There is nonetheless a lack of long-term adherence to CIC, with up to 50%
      discontinuance at 5-year follow-up. We hypothesize that limitations in upper
      extremity (UE) motor function represent a strong predictor for long-term CIC
      adoption. METHODS: We assessed Forms I and II data from the 2000-2013 National
      SCI Database. Bladder management was determined at initial discharge and 1-year
      follow-up. Upper extremity (UE) motor scores were transformed using a previously
      published algorithm to predict a patient's ability to independently self
      catheterize. Uni- and multivariable logistic regression modeling was performed to
      assess risk factors affecting: a) a lack of CIC adoption at rehabilitation
      discharge, b) CIC discontinuance by 1-year follow-up (CIC "dropout"), and c)
      adherence to management with an indwelling catheter rather than conversion to CIC
      at 1-year follow-up. RESULTS: For all three modeled scenarios, UE motor function
      represented the most significant predictor for lack of CIC adoption (OR range 2.1
      6.3, P <= 0.003 for all). Other predictors included increasing age (OR 1.01-1.02,
      P <= 0.001 for all models) and female gender (OR 1.6-1.7, P < 0.001 for lack of
      CIC adoption at discharge). CONCLUSIONS: Among physically limiting factors,
      impairment in UE motor function appears to be the most significant predictor of a
      lack of long-term CIC adoption at 1-year follow-up.

PMID- 29044680
TI  - Effects of three blood derived products on equine corneal cells, an in vitro
      study.
AB  - BACKGROUND: Despite advances in therapy of corneal ulcerative diseases in horses,
      a vast number of cases require surgical intervention, due to poor response to
      treatment. Topical application of serum has been used for many years, based on
      its anticollagenolytic properties and the presence of growth factors promoting
      corneal wound healing. However, although other blood derived products i.e.
      platelet rich plasma (PRP), plasma rich in growth factors (PRGF) have been widely
      used in equine orthopaedics and in human ophthalmology, no reports of the effects
      of these blood derived products exist in equine ophthalmology. OBJECTIVES: To
      determine in vitro effects of PRGF and PRP on equine corneal cells compared with
      serum. STUDY DESIGN: Prospective controlled cohort study. METHODS: Blood from 35
      healthy horses was used to produce serum, PRGF (Endoret(r) ), and PRP (E-PETTM).
      Limbal- and stromal cells were isolated from healthy corneas of six horses and
      treated with 20% serum, 20% PRGF or 20% PRP. Proliferation rates and migration
      capacity were analysed in single cell cultures as well as co-culture systems.
      RESULTS: Cell proliferation increased with PRP treatment, remained constant in
      PRGF treated cells, and declined upon serum treatment over a period of 48 h.
      Migration capacity was significantly enhanced with PRP treatment, compared with
      PRGF treatment. Intact leucocytes, mainly eosinophils, were only detected in PRP.
      MAIN LIMITATIONS: Due to the study design use of autologous blood products on
      corneal cells was not possible. CONCLUSIONS: The results demonstrate beneficial
      effects of PRP on proliferation as well as migration capacity of equine corneal
      cells in vitro. In vivo studies are warranted to determine further beneficial
      effects of PRP in horses with corneal ulcers.

PMID- 29044681
TI  - Does omalizumab modify a course of recalcitrant chronic spontaneous urticaria?: A
      retrospective study in Asian patients.
AB  - Omalizumab has been approved for the treatment of recalcitrant chronic
      spontaneous urticaria (CSU). However, it remains unanswered whether omalizumab
      modifies a CSU course. We aimed to study a course of CSU after omalizumab
      treatment in an Asian population. Medical records of recalcitrant CSU patients
      who attended Siriraj Hospital between 2013 and 2017 were reviewed. All patients
      receiving omalizumab treatment were followed after the first injection for at
      least 1 year. Of 15 patients receiving omalizumab treatment, 11 patients (73.3%)
      responded well to 150 mg while the rest required 300 mg. The median follow-up
      period was 18 months (range, 13.5-25.3). Three patterns of response were proposed
      and measured: excellent (disease remission over than 6 months) was found in 20%;
      good (injection interval extended longer than 6 months) was found in 27%; and
      modest (frequently required injections) was found in 53%. The mean duration of
      complete remission was 33 weeks (range, 26-38). Two-thirds of patients had
      disease relapse and required omalizumab injections to control symptoms. The other
      third did not show relapses for at least 69 weeks of the follow-up period. After
      1 year of treatment, Kaplan-Meier curves estimated that a higher percentage
      (86.7%) of recalcitrant CSU patients receiving omalizumab treatment would be free
      of symptoms (weekly Urticaria Activity Score = 0) without prednisolone and/or
      cyclosporin as compared with 42% of patients not receiving omalizumab treatment.
      In conclusion, patients seem to be easily and safely manageable with omalizumab.
      Prednisolone and cyclosporin could be discontinued in all patients. Further
      studies are needed to conclude whether omalizumab can exactly modify CSU.

PMID- 29044682
TI  - Systematic review and meta-analysis of liver transplantation using grafts from
      deceased donors aged over 70 years.
AB  - INTRODUCTION: Due to the current organ shortage, nearly 20% of patients die
      waiting for a liver transplant (LT). The average donor age is on the rise, and
      grafts from elderly donors are offered as extended criteria grafts. METHODS: This
      is a meta-analysis comparing the outcome differences of adult patients undergoing
      LT using grafts from <70-year-old donors vs >70-year-old donors. The primary end
      points were graft and patient survival. Secondary outcomes were biliary and
      vascular complications as well as graft function. The odds ratio (OR) is a
      summary statistic with the corresponding 95% confidence interval; P < .05 was
      considered to be statistically significant. RESULTS: Eight nonrandomized
      comparative studies with 4376 LT recipients were included. About 79.9% and 20.1%
      of the grafts were from <70-year-old and >70-year-old donors, respectively. Graft
      survival at 1 year was similar between the two groups (P = .11), but there was
      better 3-year and 5-year graft survival in the >70-year-old group (P = .006 and P
      < .0001, respectively). Patient survival was also similar between the groups at 1
      year (P = .54), but with better survival at 3-year and 5-year follow-ups (P =
      .007 and P < .0001, respectively) in the >70-year-old group. There were no
      statistically significant differences in the incidence of biliary, vascular, and
      graft functional-related complications. CONCLUSION: Liver grafts from selected
      >70-year-old donors do not pose added organ-specific risks and thus have
      comparable transplantation outcomes.

PMID- 29044683
TI  - The supervisory encounter and the senior GP trainee: managing for, through and
      with.
AB  - OBJECTIVE: Help-seeking supervisory encounters provide important learning
      experiences for trainees preparing for independent practice. Although there is a
      body of expert opinion and theories on how supervisor encounters should happen,
      supporting empirical data are limited. This is particularly true for the senior
      general practice (GP) trainee. Without knowing what happens during these
      encounters, we cannot know how to maximise their educational potential. This
      study aimed to understand what happens when senior GP trainees call on their
      supervisor when caring for patients and how learning can be enhanced when this
      occurs. METHODS: This is an analysis of data from a multi-case study of five GP
      supervisory pairs, each with a GP registrar and their supervisor. The data are
      recordings of 45 supervisory encounters, 78 post-encounter reflections and six
      interviews. We used Wenger's communities of practice theory and rhetorical genre
      theory as analytical lenses. RESULTS: The supervisory encounters followed a
      consistent format, which fitted the form of a genre. Within this genre, three
      dominant interactional patterns were identified, which we labelled 'managing
      for', 'managing through' and 'managing with'. Each pattern presented different
      opportunities and drew on different skills. The primary agenda was always
      developing a plan for the patient. Education agendas included acquiring
      knowledge, developing skills and achieving independence. Other agendas were
      issues of control, credibility and relationship building. Both supervisor and
      trainee could be purposeful in their supervisory engagement. CONCLUSIONS: For
      supervisors and trainees to achieve the educational potential of their
      supervisory encounters they require flexibility. This depends on understanding
      the genre of the supervisory encounter, the agendas at play, the options they
      have in engaging and having the skills to utilise these options. Educators can
      facilitate supervisors and trainees in acquiring this understanding and these
      skills. We recommend further research into the genre of the supervisory
      encounter.

PMID- 29044684
TI  - Evaluation of the Cervix After Cervical Conization by Transvaginal Elastography.
AB  - OBJECTIVES: The purpose of this study was to investigate the stiffness of the
      cervix after the loop electrosurgical excision procedure (LEEP) by transvaginal
      elastography and its potential ability to predict future pregnancy. METHODS: A
      retrospective study included patients of reproductive age who underwent LEEP for
      cervical high-grade squamous intraepithelial lesions on the basis of colposcopic
      findings and who desired fertility. The characteristics on conventional
      transvaginal ultrasonography and elastography before and 6 months after LEEP were
      reviewed and analyzed. Each case had a 12-month follow-up, and the information on
      pregnancy and a cervical cytologic examination was recorded. RESULTS: Fifty-three
      patients who completed the 12-month follow-up were included in the analysis.
      Thirty-two cases (group 1) were pregnant during the follow-up, and the other 21
      (group 2) had pregnancy failure. The cervical lengths of group 1 and 2 as
      measured by traditional transvaginal ultrasonography were similar before and 6
      months after LEEP. The resistive index of group 1 was significantly higher 6
      months after LEEP than before LEEP (mean +/- SD, 0.88 +/- 0.36 versus 0.42 +/-
      0.22; P = .007). The mean elasticity score for the cervix was statistically
      significantly lower after LEEP (2.21 +/- 0.53) than before (3.46 +/- 0.78; P =
      .001) in group 1. However, in group 2, the mean elasticity scores were similar
      after LEEP (3.19 +/- 0.58) and before (3.25 +/- 0.66; P = .75). CONCLUSIONS: Our
      results suggest that elastography was a useful technique for evaluating the
      stiffness of the cervix after LEEP. Elastography could provide a potential means
      to predict future pregnancy after LEEP.

PMID- 29044685
TI  - Involvement of NF-kappaB in the upregulation of cystathionine-gamma-lyase, a
      hydrogen sulfide-forming enzyme, and bladder pain accompanying cystitis in mice.
AB  - Hydrogen sulfide (H2 S) is generated from l-cysteine by multiple enzymes
      including cystathionine-gamma-lyase (CSE), and promotes nociception by targeting
      multiple molecules such as Cav 3.2 T-type Ca2+ channels. Bladder pain
      accompanying cyclophosphamide (CPA)-induced cystitis in mice has been shown to
      involve the functional upregulation of the CSE/H2 S/Cav 3.2 pathway. Therefore,
      we investigated whether NF-kappaB, as an upstream signal of the CSE/H2 S system,
      contributes to bladder pain in mice with CPA-induced cystitis. Bladder pain-like
      nociceptive behaviour was observed in CPA-treated mice, and referred hyperalgesia
      was evaluated by the von Frey test. Isolated bladder weights were assessed to
      estimate bladder swelling, and protein levels were measured by Western blotting.
      CPA, administered intraperitoneally, induced nociceptive behaviour, referred
      hyperalgesia and increased bladder weights in mice. beta-Cyano-l-alanine, a
      reversible selective CSE inhibitor, prevented CPA-induced nociceptive behaviour,
      referred hyperalgesia, and, in part, increases in bladder weight. CPA markedly
      increased phosphorylated NF-kappaB p65 levels in the bladder, an effect that was
      prevented by pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. PDTC and
      curcumin, which inhibits NF-kappaB signals, abolished CPA-induced nociceptive
      behaviour, referred hyperalgesia and, in part, increases in bladder weight. CPA
      caused the overexpression of CSE in the bladder, and this was prevented by PDTC
      or curcumin. The CPA-induced activation of NF-kappaB signals appeared to cause
      CSE overexpression in the bladder, contributing to bladder pain and in part
      swelling, possibly through H2 S/Cav 3.2 signaling. Therefore, NF-kappaB
      inhibiting compounds including curcumin may be useful for the treatment of
      cystitis-related bladder pain.

PMID- 29044686
TI  - Thiol-Ene Clickable Gelatin: A Platform Bioink for Multiple 3D Biofabrication
      Technologies.
AB  - Bioprinting can be defined as the art of combining materials and cells to
      fabricate designed, hierarchical 3D hybrid constructs. Suitable materials, so
      called bioinks, have to comply with challenging rheological processing demands
      and rapidly form a stable hydrogel postprinting in a cytocompatible manner.
      Gelatin is often adopted for this purpose, usually modified with (meth-)acryloyl
      functionalities for postfabrication curing by free radical photopolymerization,
      resulting in a hydrogel that is cross-linked via nondegradable polymer chains of
      uncontrolled length. The application of allylated gelatin (GelAGE) as a thiol-ene
      clickable bioink for distinct biofabrication applications is reported. Curing of
      this system occurs via dimerization and yields a network with flexible properties
      that offer a wider biofabrication window than (meth-)acryloyl chemistry, and
      without additional nondegradable components. An in-depth analysis of GelAGE
      synthesis is conducted, and standard UV-initiation is further compared with a
      recently described visible-light-initiator system for GelAGE hydrogel formation.
      It is demonstrated that GelAGE may serve as a platform bioink for several
      biofabrication technologies by fabricating constructs with high shape fidelity
      via lithography-based (digital light processing) 3D printing and extrusion-based
      3D bioprinting, the latter supporting long-term viability postprinting of
      encapsulated chondrocytes.

PMID- 29044688
TI  - NMR of ionic liquids.

PMID- 29044687
TI  - Incident ischaemic stroke and Type 2 diabetes: trends in incidence and case
      fatality in Scotland 2004-2013.
AB  - AIM: To describe trends in first ischaemic stroke incidence and case fatality in
      adults with and without a diagnosis of Type 2 diabetes prior to their ischaemic
      stroke event in Scotland between 2004 and 2013. METHODS: Using population-wide
      hospital admission, death and diabetes datasets, we conducted a retrospective
      cohort study. Negative binomial and logistic regression models were used to
      calculate year-specific incidence and case-fatality rates for people with Type 2
      diabetes and for people without diabetes. RESULTS: During 41.0 million person
      years of follow-up there were 69 757 ischaemic stroke events. Type 2 diabetes
      prevalence among patients who experienced ischaemic stroke increased from 13.5%
      to 20.3% between 2004 and 2013. Stroke incidence rates declined by 2.7% (95% CI
      2.4, 3.0) annually for people with and without diabetes [diabetes/year
      interaction: rate ratio 0.99 (95% CI 0.98, 1.01)]. Type 2 diabetes was associated
      with an increased risk of ischaemic stroke in men [rate ratio 1.23 (95% CI 1.17,
      1.30)] and women [rate ratio 1.41 (95% CI 1.35, 1.48)]. Case-fatality rates were
      14.2% and 12.7% in people with Type 2 diabetes and without diabetes,
      respectively. Case fatality declined by 3.5% (95% CI 2.7, 4.5) annually
      [diabetes/year interaction: odds ratio 1.01 (95% CI 0.98, 1.02)]. CONCLUSIONS:
      Ischaemic stroke incidence declined no faster in people with a diagnosis of Type
      2 diabetes than in people without diabetes. Increasing prevalence of Type 2
      diabetes among stroke patients may mean that declines in case fatality over time
      will be less marked in the future.

PMID- 29044689
TI  - Behead and live long or the tale of cathepsin L.
AB  - In recent decades Saccharomyces cerevisiae has proven to be one of the most
      valuable model organisms of aging research. Pathways such as autophagy or the
      effect of substances like resveratrol and spermidine that prolong the replicative
      as well as chronological lifespan of cells were described for the first time in
      S. cerevisiae. In this study we describe the establishment of an aging reporter
      that allows a reliable and relative quick screening of substances and genes that
      have an impact on the replicative lifespan. A cDNA library of the flatworm
      Dugesia tigrina that can be immortalized by beheading was screened using this
      aging reporter. Of all the flatworm genes, only one could be identified that
      significantly increased the replicative lifespan of S.cerevisiae. This gene is
      the cysteine protease cathepsin L that was sequenced for the first time in this
      study. We were able to show that this protease has the capability to degrade such
      proteins as the yeast Sup35 protein or the human alpha-synuclein protein in yeast
      cells that are both capable of forming cytosolic toxic aggregates. The
      degradation of these proteins by cathepsin L prevents the formation of these
      unfolded protein aggregates and this seems to be responsible for the increase in
      replicative lifespan.

PMID- 29044690
TI  - Apparent diffusion coefficients of the five major metabolites measured in the
      human brain in vivo at 3T.
AB  - PURPOSE: To measure the apparent diffusion coefficients (ADC) of five main
      metabolites in the human brain at 3T with PRESS and STEAM, avoiding measurement
      biases because of cross-terms. Cross-terms arise from interactions between slice
      selection and spoiler gradients in the localized spectroscopy sequence and the
      diffusion gradients. METHODS: Diffusion-weighted spectra were acquired from the
      prefrontal cortex in five healthy subjects using STEAM (echo time [TE]/mixing
      time [TM]/pulse repetition time [TR] = 21.22/105/3000 ms, b-values = 0 and 3172
      s/mm2 ) and PRESS (TE/TR = 54.2/3000 ms, b-values = 0 and 2204 s/mm2 ). Diffusion
      weighting was applied using bipolar gradients in three orthogonal directions.
      Post-processed spectra were analyzed with LCModel, and the trace/3 ADC values
      were calculated. RESULTS: Comparable trace/3 ADC values (0.14-0.18 um2 /ms) were
      obtained for five main metabolites with both methods. These metabolites were
      quantified with Cramer-Rao lower bounds below 15%. CONCLUSION: The ADC values of
      the five main metabolites were successfully measured in the human brain at 3T
      with eliminated directional dependence. Both STEAM and PRESS can be used to probe
      the diffusivity of metabolites in normal brain and various pathologies on the
      clinical scanner with slightly higher precision achieved with STEAM for glutamate
      and myo-inositol. Magn Reson Med 79:2896-2901, 2018. (c) 2017 International
      Society for Magnetic Resonance in Medicine.

PMID- 29044691
TI  - The role of magnetization transfer in the observed contrast in T1 weighted
      imaging under clinical setups.
AB  - In T1 weighted magnetic resonance imaging of brain and spinal cord in the
      clinical setting, the white matter (WM) appears with greater intensity than the
      gray matter (GM). This contrast has been assigned to differences in T1 values. In
      these experiments the RF pulses are too long to excite both the water and the
      species with restricted motion of the protons (SRMP). In in vitro studies using
      short RF pulses, the contrast is reversed, with greater intensity for the GM.
      These results raise the question of whether magnetization transfer (MT) plays a
      role in the contrast observed in the T1 weighting experiments. In the present
      work we implemented selective saturation recovery alone and together with the
      conventional magnetization transfer contrast (MTC) method. The results confirm
      that a major factor that determines the characteristic WM/GM averaged intensity
      ratio observed in T1 weighted imaging under clinical conditions is MT between the
      SRMP and water. When selective saturation recovery is combined with MTC, the SRMP
      yields spectral widths ranging from a few to tens of kilohertz, indicating that
      more than one type of SRMP is involved in the MT. The z-spectrum obtained with
      this combination is free of the effect of direct saturation of the water peak.
      Selective saturation recovery enables an independent measurement of the exchange
      time and T1 , while the combination with MTC with complete saturation of the SRMP
      enables measurement of T1 without the effect of MT. The latter measurement can be
      carried out on a timescale much shorter than T1.

PMID- 29044693
TI  - Erratum.

PMID- 29044694
TI  - A Bioethics Editor's Summer 2017 Conference Season: Conscientious Objection and
      Research Ethics.

PMID- 29044696
TI  - Relative reductions in health care utilization among young adults before aging
      out of extended dependent coverage.
AB  - The 2010 Affordable Care Act extended dependent coverage for adult children up to
      age 26 in the USA. Since then, considerable studies have assessed its various
      impacts among young adults. However, little is known about whether there is any
      change in health care use when young adults age out of dependent coverage. This
      study examines health care consumption changes among young adults prior to their
      aging out process. I used data from a large insurance claim database and studied
      health care utilization of young adults under parents' coverage during a 2-year
      period in a difference-in-difference framework. I found that young adults had
      relative reductions in health services use, except ER visits, compared with
      individuals who stayed under parents' coverage. This pattern was the same for
      both male and females. Individuals with regular medical needs had greater
      relative reductions compared with those without regular medical needs. The
      relative reductions in health care use during the aging out process may have an
      important impact on young adults' health, especially for those with regular
      medical needs. More efforts could be made to help them maintain regular medical
      utilization during the transition.

PMID- 29044695
TI  - Ectogenesis, abortion and a right to the death of the fetus.
AB  - Many people believe that the abortion debate will end when at some point in the
      future it will be possible for fetuses to develop outside the womb. Ectogenesis,
      as this technology is called, would make possible to reconcile pro-life and pro
      choice positions. That is because it is commonly believed that there is no right
      to the death of the fetus if it can be detached alive and gestated in an
      artificial womb. Recently Eric Mathison and Jeremy Davis defended this position,
      by arguing against three common arguments for a right to the death of the fetus.
      I claim that their arguments are mistaken. I argue that there is a right to the
      death of the fetus because gestating a fetus in an artificial womb when genetic
      parents refuse it violates their rights not to become a biological parent, their
      rights to genetic privacy and their property rights. The right to the death of
      the fetus, however, is not a woman's right but genetic parents' collective right
      which only can be used together.

PMID- 29044698
TI  - Methotrexate treatment in a case of juvenile pityriasis rubra pilaris.
AB  - An 8-year-old boy who was initially diagnosed with plaque psoriasis failed
      management with topical therapies and skin biopsy confirmed the suspected
      diagnosis of juvenile pityriasis rubra pilaris (PRP). Pityriasis rubra pilaris is
      a rare inflammatory disorder of the skin characterized by follicular keratotic
      papules coalescing into plaques, along with palmoplantar keratoderma. Treatment
      modalities include topical and systemic therapies, although previous studies have
      not shown much benefit with methotrexate in children. We present a case in which
      methotrexate led to significant improvement of the skin findings in a child with
      type IV juvenile pityriasis rubra pilaris.

PMID- 29044697
TI  - AtRAE1 is involved in degradation of ABA receptor RCAR1 and negatively regulates
      ABA signalling in Arabidopsis.
AB  - The phytohormone abscisic acid (ABA) plays an important role in regulating plant
      growth, development, and adaption to various environmental stresses. Regulatory
      components of ABA receptors (RCARs, also known as PYR/PYLs) sense ABA and
      initiate ABA signalling through inhibiting the activities of protein phosphatase
      2C in Arabidopsis. However, the way in which ABA receptors are regulated is not
      well known. A DWD protein AtRAE1 (for RNA export factor 1 in Arabidopsis), which
      may act as a substrate receptor of CUL4-DDB1 E3 ligase, is an interacting partner
      of RCAR1/PYL9. The physical interaction between RCAR1 and AtRAE1 is confirmed in
      vitro and in vivo. Overexpression of AtRAE1 in Arabidopsis causes reduced
      sensitivity of plants to ABA, whereas suppression of AtRAE1 causes increased
      sensitivity to ABA. Analysis of protein stability demonstrates that RCAR1 is
      ubiquitinated and degraded in plant cells and AtRAE1 regulates the degradation
      speed of RCAR1. Our findings indicate that AtRAE1 likely participates in ABA
      signalling through regulating the degradation of ABA receptor RCAR1.

PMID- 29044699
TI  - Diabetic striatopathy manifesting as severe consciousness disturbance with no
      involuntary movements.
AB  - BACKGROUND: Diabetic striatopathy, one of the complications of diabetes mellitus,
      is characterized by involuntary movements, including hemichorea and
      hemiballismus, and the presence of hyperintense lesions on T1-weighted magnetic
      resonance imaging of the striatum. CASE REPORT: We present a case of diabetic
      striatopathy manifesting as severe consciousness disturbance without chorea or
      ballismus. A 58-year-old man was admitted to our hospital in a state of
      unconsciousness. He was diagnosed with diabetic striatopathy as a result of
      extremely elevated blood glucose levels and typical magnetic resonance imaging
      findings in the left striatum, although involuntary movements were absent. He was
      treated with insulin, and his glucose levels were well maintained. His
      neuropsychiatric symptoms recovered, rather slowly but completely, after ~20
      days. CONCLUSION: This case indicates the diversity of striatal dysfunction
      induced by hyperglycaemia. For good prognosis of diabetic striatopathy, prompt
      diagnosis and appropriate treatments are important. Physicians should be aware
      that this disease can cause various neurological and psychiatric symptoms other
      than chorea or ballismus.

PMID- 29044700
TI  - Epidermal nevus syndromes: New insights into whorls and swirls.
AB  - Knowledge of the molecular underpinnings of many epidermal nevi and epidermal
      nevus syndrome has expanded rapidly in recent years. In this review and update on
      epidermal nevus syndrome, we will cover recent genetic discoveries involving
      epidermal nevi, including nevus sebaceus, keratinocytic epidermal nevus, nevus
      comedonicus, congenital hemidysplasia with ichthyosiform nevus and limb defects
      syndrome, phakomatosis pigmentokeratotica, Becker's nevus, porokeratotic adnexal
      ostial nevus, inflammatory linear verrucous epidermal nevi, and cutaneous
      skeletal hypophosphatemia syndrome. We will discuss how newly defined mutations
      relate to the biology reflected in the cutaneous patterns seen in these mosaic
      disorders and how new molecular data has informed our understanding of these
      diseases and shaped management decisions.

PMID- 29044701
TI  - Malignant PEComa.

PMID- 29044702
TI  - Risk of pre-eclampsia in women taking metformin: a systematic review and meta
      analysis.
AB  - AIMS: To perform meta-analyses of studies evaluating the risk of pre-eclampsia in
      high-risk insulin-resistant women taking metformin prior to, or during pregnancy.
      METHODS: A search was conducted of the Medline, EMBASE, Web of Science and Scopus
      databases. Both randomized controlled trials and prospective observational cohort
      studies of metformin treatment vs. placebo/control or insulin either prior to or
      during pregnancy were selected. The main outcome measure was the incidence of pre
      eclampsia in each treatment group. RESULTS: Overall, in five randomized
      controlled trials comparing metformin treatment (n = 611) with placebo/control (n
      = 609), no difference in the risk of pre-eclampsia was found [combined/pooled
      risk ratio (RR), 0.86 (95% CI 0.33-2.26); P = 0.76; I2  = 66%]. Meta-analysis of
      four cohort studies again showed no significant effect [RR, 1.21 (95% CI 0.56
      2.61); P = 0.62; I2  = 30%]. A meta-analysis of eight randomized controlled
      trials comparing metformin (n = 838) with insulin (n = 836), however, showed a
      reduced risk of pre-eclampsia with metformin [RR, 0.68 (95% CI 0.48-0.95); P =
      0.02; I2  = 0%]. No heterogeneity was present in the metformin vs. insulin
      analysis of randomized controlled trials, whereas high levels of heterogeneity
      were present in studies comparing metformin with placebo/control. Pre-eclampsia
      was a secondary outcome in most of the studies. The mean weight gain from time of
      enrolment to delivery was lower in the metformin group (P = 0.05, metformin vs.
      placebo; P = 0.004, metformin vs. insulin). CONCLUSIONS: In studies randomizing
      pregnant women to glucose-lowering therapy, metformin was associated with lower
      gestational weight gain and a lower risk of pre-eclampsia compared with insulin.

PMID- 29044703
TI  - A comparative study on the effect of promoting the osteogenic function of
      osteoblasts using isoflavones from Radix Astragalus.
AB  - Radix Astragalus has been shown to exert beneficial effects regarding the
      prevention postmenopausal osteoporosis. However, its mechanism of action remains
      to be investigated. Calycosin, formononetin, and calycosin-7-O-beta-d-glucoside
      are the main isoflavone constituents of Astragalus. In this study, the abilities
      of these 3 compounds to promote osteogenic function of osteoblasts were compared,
      and the structure-activity relationships of these osteotrophic isoflavones were
      determined. Calycosin exhibited a greater effect than formononetin and calycosin
      7-O-beta-d-glucoside regarding improvements in osteogenic function of
      osteoblasts, as demonstrated by cell proliferation, alkaline phosphatase
      activity, collagen I and osteocalcin secretion, and the number and area of
      mineralized bone nodules. This suggests that calycosin may be better than
      formononetin and calycosin-7-O-beta-d-glucoside at preserving bone mass. In
      addition, calycosin, formononetin, and calycosin-7-O-beta-d-glucoside stimulate
      the expression of bone morphogenetic protein 2 and runt-related transcription
      factor 2 proteins, which indicates that all 3 agents may promote the osteogenesis
      of osteoblasts via regulation of bone morphogenetic protein 2 expression. In
      conclusion, calycosin may be the best candidate, with higher osteogenic activity
      than formononetin and calycosin-7-O-beta-d-glucoside. The higher osteogenic
      activity of calycosin could be attributable to the superiority of its chemical
      structure (a hydroxyl group at position C3 of Ring B and no glucosyl group).

PMID- 29044704
TI  - Biomimetic Inspired Core-Canopy Quantum Dots: Ions Trapped in Voids Induce
      Kinetic Fluorescence Switching.
AB  - Closely packed hollow spheres connected through pillars to a CdSe quantum dot
      (QD) core produce channels through which ions navigate. This particular structure
      is well represented by [CdSe@CarbOPH(O)]@Cl/[N(Caprylyl)3 Me1 ] indicating that
      in the channels between the canopy made by the carboranyl spheres
      (carboranylphosphinate, CarbOPH(O)) and the CdSe core exist chloride anions. Due
      to the close packing, the spheres produce openings. These are converted into
      gates because [N(Caprylyl)3 Me1 ] acts as a plug. The
      [CdSe@CarbOPH(O)]@Cl/assembly is negatively charged because the Cd positive
      charges are outnumbered by the negative charges due to the Se, the phosphinic
      acid and, very importantly, the trapped chloride anions, and this negative load
      is compensated by the cationic surfactant. Here, it is shown that this synergism
      produces an unprecedented phenomenon, namely, kinetic fluorescence switching. It
      is observed that the material shines brightly then loses its brightness and, upon
      the application of kinetic energy, shines back to the maximum power. This process
      continues for an extended period of time, up to half a year, at least. This new
      type of architecture in QDs is named as core-canopy QDs. In this case, this study
      demonstrates one property, the kinetic fluorescence switching, as a consequence
      of the trapping of Cl- in the QDs channels, but other properties can be envisaged
      with the judicious choice of the anions or even the pillar connecting the hollow
      sphere with the ground.

PMID- 29044705
TI  - Subchondral Trabecular Rod Loss and Plate Thickening in the Development of
      Osteoarthritis.
AB  - Developing effective treatment for osteoarthritis (OA), a prevalent and disabling
      disease, has remained a challenge, primarily because of limited understanding of
      its pathogenesis and late diagnosis. In the subchondral bone, rapid bone loss
      after traumatic injuries and bone sclerosis at the advanced stage of OA are well
      recognized hallmarks of the disease. Recent studies have further demonstrated the
      crucial contribution of subchondral bone in the development of OA. However, the
      microstructural basis of these bone changes has not been examined thoroughly, and
      the paradox of how abnormal resorption can eventually lead to bone sclerosis
      remains unanswered. By applying a novel microstructural analysis technique,
      individual trabecula segmentation (ITS), to micro-computed tomography (MUCT)
      images of human OA knees, we have identified a drastic loss of rod-like
      trabeculae and thickening of plate-like trabeculae that persisted in all regions
      of the tibial plateau, underneath both severely damaged and still intact
      cartilage. The simultaneous reduction in trabecular rods and thickening of
      trabecular plates provide important insights to the dynamic and paradoxical
      subchondral bone changes observed in OA. Furthermore, using an established guinea
      pig model of spontaneous OA, we discovered similar trabecular rod loss and plate
      thickening that preceded cartilage degradation. Thus, our study suggests that rod
      and-plate microstructural changes in the subchondral trabecular bone may play an
      important role in the development of OA and that advanced microstructural
      analysis techniques such as ITS are necessary in detecting these early but subtle
      changes. With emerging high-resolution skeletal imaging modalities such as the
      high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular
      rod loss identified by ITS could potentially be used as a marker in assessing the
      progression of OA in future longitudinal studies or clinical diagnosis. (c) 2017
      American Society for Bone and Mineral Research.

PMID- 29044706
TI  - Expression of inflammatory and structural matrix genes in synovial fluid
      following intra-articular administration of isoflupredone acetate to exercised
      horses.
AB  - BACKGROUND: Intra-articular use of corticosteroids is commonplace in performance
      horses. Isoflupredone acetate (IPA) is one of four Food and Drug Administration
      approved corticosteroids for intra-articular use in horses. The lack of published
      reports describing the efficacy and duration of effects of this drug warrant
      further study. OBJECTIVES: To assess the effects of intra-articular
      administration of IPA on the expression of selected anti- and pro-inflammatory
      and structural matrix genes following intra-articular administration to exercised
      Thoroughbred horses and to correlate these effects with drug concentrations.
      STUDY DESIGN: Block design in vivo experiment. METHODS: Twelve exercised horses
      received either a single intra-articular administration of 8 mg of IPA or 0.9%
      saline solution. Synovial fluid samples were collected prior to and up to 42 days
      post drug administration from the treated joints. Microarray and qRT-PCR analysis
      were used to assess changes in expression levels of various inflammatory and
      structural genes post drug administration. RESULTS: On microarray analysis, 855,
      23,358 and 26,411 genes had a measurable fold change (increase or decrease in
      expression levels) when comparing baseline samples to 24 h, baseline samples to
      day 7 and 24 h samples to day 7, respectively. Of the genes selected for further
      study by qRT-PCR analysis, expression of ANXA-1 (lipocortin) was significantly
      increased and IL23A and MMP1 and MMP9 significantly decreased following IPA
      administration. Expression levels of collagen genes were not significantly
      different from baseline. MAIN LIMITATIONS: Limitations include the use of a
      noninflammatory model as results may differ in the presence of an acute
      inflammatory insult and the inability to measure protein concentrations of
      inflammatory mediators due to limited synovial fluid sample volume. CONCLUSIONS:
      Expression relative to baseline, for both inflammatory and matrix genes for up to
      42 days post IPA administration, suggests a prolonged effect relative to
      detection time in both plasma and synovial fluid.

PMID- 29044707
TI  - The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic
      Kidney Disease.
AB  - Use of active forms of vitamin D is advocated in patients with chronic kidney
      disease (CKD) for treatment of mineral bone disease because of the presumption
      that native forms of vitamin D would not undergo significant activation to
      calcitriol, the most active biological form of vitamin D. We present secondary
      analysis looking at bone turnover in subjects who completed the randomized,
      double blind, placebo-controlled trial investigating the effect of
      cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3
      G4 and vitamin D <=20 ng/mL (Clinical Trials Registry of India:
      CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two
      directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo
      at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol
      group and 59 in the placebo group completed the study. At 16 weeks, the serum
      25(OH)D and 1,25(OH)2 D levels increased in the cholecalciferol group but not in
      the placebo group (between-group difference in mean change: 23.40 ng/mL; 95% CI,
      19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007,
      respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol
      group (between-group difference in mean change -100.73 pg/mL (95% CI, -150.50 to 
      50.95; p < 0.001). Serum total and bone-specific alkaline phosphatase (SAP, BAP)
      and serum C-terminal cross-linked collagen type I telopeptides (CTX-1) were
      significantly reduced in cholecalciferol group (between group difference for
      change in mean: -20.25 U/L; 95% CI, -35.14 to -5.38 U/L; p = 0.008 for SAP; 
      12.54 U/L; 95% CI, -22.09 to -2.98 U/L; p = 0.013 for BAP; and -0.21 ng/mL; 95%
      CI, -0.38 to -0.05 ng/mL; p = 0.05 for CTX-1). Correlation analysis showed
      significant correlation of Delta25(OH)D with DeltaiPTH (r = -0.409, p < 0.0001),
      Delta1,25(OH)2 D (r = 0.305, p = 0.001), DeltaSAP (r = -0.301, p = 0.002),
      DeltaBAP (r = -0.264, p = 0.004), and DeltaCTX-1 (r = -0.210, p = 0.0230).
      Cholecalciferol supplementation corrects vitamin D deficiency and is effective in
      lowering serum intact parathyroid hormone and bone turnover markers in early
      stages of CKD. (c) 2017 American Society for Bone and Mineral Research.

PMID- 29044709
TI  - The Complex Solid-State Landscape of Sodium Diatrizoate Hydrates.
AB  - Pharmaceutical sodium salts are prone to incorporate water into their crystal
      structures. The model compound diatrizoic acid monosodium salt, an X-ray contrast
      agent, has been investigated in depth towards its interaction with water in the
      solid state. Five hydrates with water content ranging from 0.3 to 8 molar
      equivalents of water show a high degree of interconvertibility, stoichiometric
      and non-stoichiometric behaviour, and potential of amorphisation during release
      of water. A DMSO/water mixed solvate further highlights the high attraction of
      this salt to incorporate water. All incorporated solvent coordinates to the
      sodium cation and can further interact and stabilise the respective crystal forms
      by hydrogen bonding. DTS thus highlights the importance of an in-depth
      investigation of sodium salts used pharmaceutically to guarantee dose uniformity
      and stability of final formulation.

PMID- 29044708
TI  - Optimal prandial timing of bolus insulin in diabetes management: a review.
AB  - The inability to achieve optimal diabetes glucose control in people with diabetes
      is multifactorial, but one contributor may be inadequate control of postprandial
      glucose. In patients treated with multiple daily injections of insulin, both the
      dose and timing of meal-related rapid-acting insulin are key factors in this.
      There are conflicting opinions and evidence on the optimal time to administer
      mealtime insulin. We performed a comprehensive literature search to review the
      published data, focusing on the use of rapid-acting insulin analogues in patients
      with Type 1 diabetes. Pharmacokinetic and pharmacodynamic studies of rapid-acting
      insulin analogues, together with postprandial glucose excursion data, suggest
      that administering these 15-20 min before food would provide optimal postprandial
      glucose control. Data from clinical studies involving people with Type 1 diabetes
      receiving structured meals and rapid-acting insulin analogues support this,
      showing a reduction in post-meal glucose levels of ~30% and less hypoglycaemia
      when meal insulin was taken 15-20 min before a meal compared with immediately
      before the meal. Importantly, there was also a greater risk of postprandial
      hypoglycaemia when patients took rapid-acting analogues after eating compared
      with before eating.

PMID- 29044710
TI  - Tracking the Progression of Osteolytic and Osteosclerotic Lesions in Mice Using
      Serial In Vivo MUCT: Applications to the Assessment of Bisphosphonate Treatment
      Efficacy.
AB  - The metastasis of tumor cells to bone can lead to osteolytic and osteosclerotic
      lesions, which cause severe, highly-localized bone destruction and abnormal bone
      apposition, respectively. Accurate quantification of lesion progression is
      critical to understand underlying mechanisms and assess treatment efficacy;
      however, standard structural parameters may be insensitive to local changes. We
      developed methods to quantify osteolytic and osteosclerotic lesions using micro
      computed tomography (MUCT) within in vivo mouse datasets. Two Balb/c nude
      datasets were used: (i) bone-homing MDA-MB-231 (osteolytic) cells injected into
      the left ventricle, treatment with alendronate or vehicle, and weekly MUCT
      (proximal tibia) for 4 weeks, and (ii) MCF7 (osteosclerotic) cells injected into
      the right tibia and weekly MUCT over 12 weeks. After registering images to
      baseline, osteolytic lesion volume was determined by summing all baseline bone
      voxels at distances greater than a threshold (150 MUm) from the nearest follow
      up. Osteosclerotic lesions were determined by measuring the distance from each
      follow-up surface voxel to the nearest baseline surface and calculating the
      standard deviation of distance values (SDDT) of the surrounding voxels. Bone
      mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were
      determined for comparison. Osteolytic lesions were observed 1 week after tumor
      cell injection; however, no corresponding BV/TV losses or Sp increases were
      observed, indicating that standard parameters were unable to detect early
      metastatic changes. Lesion volume was smaller in the alendronate versus control
      group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at weeks 3
      and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed
      following injection, providing a potential new measure of osteosclerotic bone
      apposition. These data show that quantification of local structural change with
      serial MUCT may overcome the limitations of standard mineral and microstructural
      parameters, and successfully separates metastatic and normal bone turnover. (c)
      2017 American Society for Bone and Mineral Research.

PMID- 29044711
TI  - The surgical anatomy of the sural nerve: An ultrasound study.
AB  - The aim of this study was (a) to examine the anatomy of the sural nerve (SN) in a
      sample of 30 patients and (b) to analyze the incidence of different origins of
      the SN, and the distance of the SN from planned arthroscopic portals. An
      ultrasound (USG) examination of the SN was performed bilaterally on thirty
      healthy patients with no history of surgery or trauma of the lower limb. The SNs
      were classified into six main types of pattern, with an additional category for
      new and unclassified types. Each of Types 1 and 3 had two subdivisions. The
      distances from the superior border of the calcaneal tuberosity to the three
      simulated arthroscopy portal sites (Z1, Z1.5, Z2) to the SN were measured. A
      total of 30 patients (n = 60 limbs) with an average age of 27 +/- 7.5 years were
      examined and the SN was visualized in all cases. The most common origin was Type
      3A, accounting for 30% of limbs. Type 2 was the second most common seen in 18.3%.
      The distances of the SN from arthroscopic portal placement sites above the
      lateral malleolus were 2.07 +/- 0.39 cm at the Z1 portal, 2.15 +/- 0.38 cm at
      Z1.5, and 2.28 +/- 0.33 cm at Z2. The variability in the anatomy of the SN
      warrants the use of USG to locate it accurately, thus preventing iatrogenic
      injury when portals are placed for arthroscopy, improving proper administration
      of anesthesia, and helping to localize the nerve for graft harvesting. Clin.
      Anat. 31:450-455, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29044712
TI  - Inferring the geographic origin of a range expansion: Latitudinal and
      longitudinal coordinates inferred from genomic data in an ABC framework with the
      program x-origin.
AB  - Climatic or environmental change is not only driving distributional shifts in
      species today, but it has also caused distributions to expand and contract in the
      past. Inferences about the geographic locations of past populations especially
      regions that served as refugia (i.e., source populations) and migratory routes
      are a challenging endeavour. Refugial areas may be evidenced from fossil records
      or regions of temporal stability inferred from ecological niche models. Genomic
      data offer an alternative and broadly applicable source of information about the
      locality of refugial areas, especially relative to fossil data, which are either
      unavailable or incomplete for most species. Here, we present a pipeline we
      developed (called x-origin) for statistically inferring the geographic origin of
      range expansion using a spatially explicit coalescent model and an approximate
      Bayesian computation testing framework. In addition to assessing the probability
      of specific latitudinal and longitudinal coordinates of refugial or source
      populations, such inferences can also be made accounting for the effects of
      temporal and spatial environmental heterogeneity, which may impact migration
      routes. We demonstrate x-origin with an analysis of genomic data collected in the
      Collared pika that underwent postglacial expansion across Alaska, as well as
      present an assessment of its accuracy under a known model of expansion to
      validate the approach.

PMID- 29044713
TI  - Investigation of umbilical venous vessels anatomy and diameters as a guideline
      for catheter placement in newborns.
AB  - Umbilical cord catheters (UCC) are important for the primary care of critically
      ill newborns. To analyze anatomical variations of the umbilical vein (UV) and its
      further course, we performed abdominal spiral-CT examinations on stillborns. The
      aim of the study was to explore the high incidence of mal-positioned UCCs and to
      improve their positioning. Eighteen stillborns were investigated (29.2 weeks +/-
      6.7 weeks (IQR)). CTs were performed using either air or contrast medium
      injection into the UV. We measured the diameter at the narrowest points of (i)
      the umbilical vein, (ii) the segmental portal vein, (iii) the left portal vein,
      (iv) the umbilical recess, and (v) the ductus venosus. The branching angles
      between (a) the umbilical vein and intrahepatic veins and (b) the ductus venosus
      and umbilical recess were measured. The diameter of the UV increases from 3.4 to
      11 mm (median [IQR]:4.6 mm [4.2-6.9]: r2  = 0.64). The left portal vein has a
      larger diameter (3.6 mm [2.6-4.55]; r2  = 0.43) than the left segmental portal
      vein (2.3 mm [1.8-2.75]; r2  = 0.23). The diameter of the ductus venosus (2.5 mm
      [1.6-3.4]; r2  = 0.59) is half that of the umbilical recess (5.1 mm [3.3-6.2]; r2
      = 0.43). The most obtuse angle is formed by the junction between the umbilical
      recess and ductus venosus (151 degrees  [133-159]; r2  = 0.001). The branch angle
      from the outgoing UV into the left portal vein is more obtuse (128 degrees  [123
      144]; r2  = 0.0001) than that of the segmental portal vein (115 degrees  [105
      119]; r2  = 0.0001). To avoid mal-positioning, our data suggest the use of a soft
      catheter. The UV and its extensions are wide enough to admit a 4 Fr. catheter
      without complete obstruction. Clin. Anat. 31:269-274, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29044714
TI  - Definition and classification of evaluation units for tertiary structure
      prediction in CASP12 facilitated through semi-automated metrics.
AB  - For assessment purposes, CASP targets are split into evaluation units. We herein
      present the official definition of CASP12 evaluation units (EUs) and their
      classification into difficulty categories. Each target can be evaluated as one EU
      (the whole target) or/and several EUs (separate structural domains or groups of
      structural domains). The specific scenario for a target split is determined by
      the domain organization of available templates, the difference in server
      performance on separate domains versus combination of the domains, and visual
      inspection. In the end, 71 targets were split into 96 EUs. Classification of the
      EUs into difficulty categories was done semi-automatically with the assistance of
      metrics provided by the Prediction Center. These metrics account for sequence and
      structural similarities of the EUs to potential structural templates from the
      Protein Data Bank, and for the baseline performance of automated server
      predictions. The metrics readily separate the 96 EUs into 38 EUs that should be
      straightforward for template-based modeling (TBM) and 39 that are expected to be
      hard for homology modeling and are thus left for free modeling (FM). The
      remaining 19 borderline evaluation units were dubbed FM/TBM, and were inspected
      case by case. The article also overviews structural and evolutionary features of
      selected targets relevant to our accompanying article presenting the assessment
      of FM and FM/TBM predictions, and overviews structural features of the hardest
      evaluation units from the FM category. We finally suggest improvements for the EU
      definition and classification procedures.

PMID- 29044715
TI  - Bayesian genome-wide association analysis for body weight in farmed Atlantic
      salmon (Salmo salar L.).
AB  - We performed a genome-wide association study to detect markers associated with
      growth traits in Atlantic salmon. The analyzed traits included body weight at
      tagging (BWT) and body weight at 25 months (BW25M). Genotypes of 4662 animals
      were imputed from the 50K SNP chip to the 200K SNP chip using fimpute software.
      The markers were simultaneously modeled using Bayes C to identify genomic regions
      associated with the traits. We identified windows explaining a maximum of 3.71%
      and 3.61% of the genetic variance for BWT and BW25M respectively. We found
      potential candidate genes located within the top ten 1-Mb windows for BWT and
      BW25M. For instance, the vitronectin (VTN) gene, which has been previously
      reported to be associated with cell growth, was found within one of the top ten 1
      Mb windows for BWT. In addition, the WNT1-inducible-signaling pathway protein 3,
      melanocortin 2 receptor accessory protein 2, myosin light chain kinase,
      transforming growth factor beta receptor type 3 and myosin light chain 1 genes,
      which have been reported to be associated with skeletal growth in humans, growth
      stimulation during the larval stage in zebrafish, body weight in pigs, feed
      conversion in chickens and growth rate of sheep skeletal muscle respectively,
      were found within some of the top ten 1-Mb windows for BW25M. These results
      indicate that growth traits are most likely controlled by many variants with
      relatively small effects in Atlantic salmon. The genomic regions associated with
      the traits studied here may provide further insight into the functional regions
      underlying growth traits in this species.

PMID- 29044716
TI  - Effect of central corneal thickness on intraocular pressure and comparison of
      Topcon CT-80 non-contact tonometry with Goldmann applanation tonometry.
AB  - BACKGROUND: To compare intraocular pressure (IOP) measurements obtained with the
      Topcon CT-80 non-contact tonometer (NCT) and Goldmann applanation tonometer
      (GAT), in different ranges of IOP in normal and glaucoma subjects, and to assess
      the influence of central corneal thickness (CCT) on the IOP measurements in Asian
      Indian eyes. METHODS: Four hundred and two eyes of 402 subjects (193 newly
      diagnosed primary open angle glaucoma [POAG] and 209 normal) were enrolled for
      this prospective study. For each eye, IOP was measured with GAT by a glaucoma
      specialist and NCT by a trained optometrist. The IOP values were compared among
      the tonometers in the three different IOP ranges (<= 12 mmHg, 13-20 mmHg and >=
      21 mmHg) using Bland-Altman graphs. Correlation between GAT and NCT was assessed
      by Pearson correlation co-efficient. CCT was measured with ultrasound pachymetry
      and its correlation with GAT and NCT was analysed using linear regression
      analysis. RESULTS: The mean paired difference of IOP between NCT and GAT was
      1.556 +/- 2.69 mmHg (r = 0.26, p = 0.006) at IOP range of <= 12 mmHg, -1.665 +/-
      2.6 mmHg (r = 0.51, p < 0.0001) in IOP range of 13-20 mmHg and -2.202 +/- 3.44
      mmHg (r = 0.82, p < 0.0001) in the IOP range of >= 21 mmHg. Linear regression
      analysis showed a mean IOP variation of 0.27 mmHg per 10 MUm change in CCT for
      NCT (p < 0.0001) and IOP change of 0.19 mmHg per 10 MUm change in CCT for GAT (p
      = 0.01). CONCLUSION: In this study of normotensive and POAG subjects, the Topcon
      CT-80 NCT showed an overestimation of IOP at the lower range and underestimation
      of IOP in normal and higher ranges of IOP. Clinicians should keep in mind that
      CCT influences IOP measurement with both types of tonometer and that the IOP
      readings obtained with these tonometers are not interchangeable.

PMID- 29044717
TI  - A genome-scale analysis of mRNAs targeting to plant mitochondria: upstream AUGs
      in 5' untranslated regions reduce mitochondrial association.
AB  - Intracellular sorting of mRNAs is an essential process for regulating gene
      expression and protein localization. Most mitochondrial proteins are nuclear
      encoded and imported into the mitochondria through post-translational or co
      translational processes. In the latter case, mRNAs are found to be enriched in
      the vicinity of mitochondria. A genome-scale analysis of mRNAs associated with
      mitochondria has been performed to determine plant cytosolic mRNAs targeted to
      the mitochondrial surface. Many messengers encoding mitochondrial proteins were
      found associated with mitochondria. These mRNAs correspond to particular
      functions and complexes, such as respiration or mitoribosomes, which indicates a
      coordinated control of mRNA localization within metabolic pathways. In addition,
      upstream AUGs in 5' untranslated regions (UTRs), which modulate the translation
      efficiency of downstream sequences, were found to negatively affect the
      association of mRNAs with mitochondria. A mutational approach coupled with in
      vivo mRNA visualization confirmed this observation. Moreover, this technique
      allowed the identification of 3'-UTRs as another essential element for mRNA
      localization at the mitochondrial surface. Therefore, this work offers new
      insights into the mechanism, function and regulation of the association of
      cytosolic mRNAs with plant mitochondria.

PMID- 29044719
TI  - Alkyl and Aryl Thiol Addition to [1.1.1]Propellane: Scope and Limitations of a
      Fast Conjugation Reaction.
AB  - Herein the addition of different thiols to the strained carbon-carbon bond of
      [1.1.1]propellane (1) is reported. The reaction pathway was investigated,
      addition reactions with substituted thiols, hydrogen sulfide and protected
      cysteine were performed, and further modifications of the products were verified.
      The clean reaction proceeds by a radical chain process, which was confirmed by
      different deuterium labelling experiments. It shows high functional-group
      tolerance, since halo-, hydroxy-, methoxy-, carboxy-, amino- and nitro
      substituted thiols could be added to 1 with few by-products in 16-90 % yield.
      Oxidation of the products allows tuning of the polarity and subsequent reactions
      of the products. The click-type reaction proceeds even faster with selenols, as
      was shown in a proof of concept. Thiol addition to 1 offers a facile tool for
      surface modification, conjugation and tuning of hydrophilicity in bio- and
      medicinal chemistry.

PMID- 29044718
TI  - Child- and Family-Focused Cognitive Behavioral Therapy for Pediatric Bipolar
      Disorder: Applications for Suicide Prevention.
AB  - Despite high rates of suicide ideation (SI) and behavior in youth with pediatric
      bipolar disorder (PBD), little work has examined how psychosocial interventions
      impact suicidality among this high-risk group. The current study examined SI
      outcomes in a randomized clinical trial comparing Child- and Family-Focused
      Cognitive Behavioral Therapy (CFF-CBT) for PBD versus psychotherapy treatment-as
      usual (TAU). Although not designed for suicide prevention, CFF-CBT addresses
      child and family factors related to suicide risk and thus was hypothesized to
      generalize to the treatment of suicidality. Participants included 71 youth aged 7
      13 years (M = 9.17, SD = 1.60) with DSM-IV-TR bipolar I, II, or not otherwise
      specified randomly assigned, with parent(s), to receive CFF-CBT or TAU. Both
      treatments consisted of 12 weekly and 6 monthly booster sessions. Suicide
      ideation was assessed via clinician interview at baseline, posttreatment, and 6
      month follow-up. Results indicated that SI was prevalent pretreatment: 39% of
      youth reported current suicidal thoughts. All youth significantly improved in the
      likelihood and intensity of ideation across treatment, but group differences were
      not significant. Thus, findings suggest that early intervention for these high
      risk youth may reduce SI, and at this stage of suicidality, youth may be
      responsive to even nonspecialized treatment.

PMID- 29044720
TI  - Observational Comparative Effectiveness of Pharmaceutical Treatments for Obesity
      within the Veterans Health Administration.
AB  - STUDY OBJECTIVE: To compare the effectiveness of weight-management medications
      used to assist with weight loss in real-world clinical practice in the Veterans
      Health Administration (VHA). DESIGN: Retrospective, multicenter, observational
      cohort study. DATA SOURCE: National VA Corporate Data Warehouse. PATIENTS: A
      total of 66,035 VA patients aged 18 years or older with a body mass index of 25
      kg/m2 or greater who had an initial fill for a study medication (orlistat [6153
      patients], phentermine [304 patients], lorcaserin [298 patients], or phentermine
      topiramate extended release [233 patients]) or participation in the VA's MOVE!
      weight-management program with at least three total visits in a clinic coded as a
      MOVE clinic in the subsequent 24 weeks (59,047 patients) between January 1, 2012,
      and July 1, 2016. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the
      percentage change in weight from baseline to at least 20 weeks or later (i.e.,
      closest weight to 6 months). Secondary outcomes were difference in the percentage
      of weight loss at 12 and 36 weeks; changes in blood pressure, hemoglobin A1c ,
      high-density and low-density lipoprotein cholesterol and triglyceride levels; and
      percentage of patients who achieved at least a 5% and 10% weight loss at 6 months
      from baseline in each group after at least 20 weeks. For the primary outcome, the
      percentage decrease in weight from baseline after at least 20 weeks in the
      lorcaserin, phentermine-topiramate, phentermine, orlistat, and MOVE! groups were
      3.6%, 4.1%, 3.6%, 2.1%, and 1.6%, respectively (phentermine-topiramate group vs.
      MOVE! group, p<0.05). Achievement of at least a 5% weight loss after at least 20
      weeks differed significantly among groups, ranging from 26.2% for the MOVE!
      Program only group to 40.3% for patients in the phentermine-topiramate group.
      CONCLUSION: In the VA population, the effectiveness of four available weight
      management medications was similar. Patients receiving phentermine-topiramate had
      a greater proportion of weight loss after at least 20 weeks compared with those
      solely enrolled in the VA's MOVE! weight-management program.

PMID- 29044721
TI  - Body diffusion-weighted imaging using magnetization prepared single-shot fast
      spin echo and extended parallel imaging signal averaging.
AB  - PURPOSE: This work demonstrates a magnetization prepared diffusion-weighted
      single-shot fast spin echo (SS-FSE) pulse sequence for the application of body
      imaging to improve robustness to geometric distortion. This work also proposes a
      scan averaging technique that is superior to magnitude averaging and is not
      subject to artifacts due to object phase. THEORY AND METHODS: This single-shot
      sequence is robust against violation of the Carr-Purcell-Meiboom-Gill (CPMG)
      condition. This is achieved by dephasing the signal after diffusion weighting and
      tipping the MG component of the signal onto the longitudinal axis while the non
      MG component is spoiled. The MG signal component is then excited and captured
      using a traditional SS-FSE sequence, although the echo needs to be recalled prior
      to each echo. Extended Parallel Imaging (ExtPI) averaging is used where coil
      sensitivities from the multiple acquisitions are concatenated into one large
      parallel imaging (PI) problem. The size of the PI problem is reduced by SVD-based
      coil compression which also provides background noise suppression. This sequence
      and reconstruction are evaluated in simulation, phantom scans, and in vivo
      abdominal clinical cases. RESULTS: Simulations show that the sequence generates a
      stable signal throughout the echo train which leads to good image quality. This
      sequence is inherently low-SNR, but much of the SNR can be regained through scan
      averaging and the proposed ExtPI reconstruction. In vivo results show that the
      proposed method is able to provide diffusion encoded images while mitigating
      geometric distortion artifacts compared to EPI. CONCLUSION: This work presents a
      diffusion-prepared SS-FSE sequence that is robust against the violation of the
      CPMG condition while providing diffusion contrast in clinical cases. Magn Reson
      Med 79:3032-3044, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29044722
TI  - Alopecic and aseptic nodule of the scalp in a girl.
AB  - Alopecic and aseptic nodule of the scalp is a rare entity characterized by the
      presence of nodules or cysts with sterile punctured material and negative
      cultures accompanied by nonscarring alopecia in the scalp of young men. We
      describe a case in which an 11-year-old girl presented with a nodular, fluctuant,
      round lesion on the vertex with localized alopecia. High-resolution ultrasound
      showed a hypoechoic lesion with increased flow on Doppler imaging and culture of
      the citrine-yellowish material obtained by puncture was negative. The patient
      showed complete clinical response to treatment with topical indomethacin.

PMID- 29044723
TI  - The effects of crown venting or pre-cementing of CAD/CAM-constructed all-ceramic
      crowns luted on YTZ implants on marginal cement excess.
AB  - OBJECTIVES: The purpose of this study was to analyze the cement excess produced
      when cementing CAD/CAM-fabricated lithium disilicate (L) or zirconium dioxide (Z)
      crowns using adhesive cement (A) or resin-modified glass ionomer cement (B).
      Three different cementation techniques were applied: palatal venting (PV), pre
      cementation with custom analogs (CA), and conventional standard procedure (SP).
      MATERIALS AND METHODS: Seventy-two crowns (36 each material) were assigned to 12
      experimental groups depending on the restoration material (L, Z), type of cement
      (A, B), and cementation technique (PV, CA, SP). Weight measurements were taken
      during cementation, and the amounts of excess cement, cement retained in crown,
      and relative excess cement were calculated and statistically analyzed. RESULTS: A
      significant direct relation between the amounts of cement applied and excess
      cement was observed in groups CA and SP. Vented crowns showed least amounts of
      marginal excess cement (0.8 +/- 0.3 MUl) followed by CA (4.2 +/- 1.1 MUl) and SP
      (8.8 +/- 2.5 MUl; p < .001). In CA, 32.1% less excess cement (95%CI: 28.4, 35.7)
      was produced than in the SP group (p < .001), but 27.4% more than in the PV group
      (95%CI: 23.8,31.0; p < .001). Overall, slightly smaller amounts of adhesive
      cement (A) than of glass ionomer cement (B) were retained in crowns. CONCLUSIONS:
      Using crown venting was the most effective measure to reduce the amount of
      marginal excess cement, followed using a pre-cementation device. To keep the
      marginal excess cement of one-piece zirconia implants to a minimum, both
      techniques should be considered for clinical application.

PMID- 29044725
TI  - Serum Sclerostin Levels in Adults With Osteogenesis Imperfecta: Comparison With
      Normal Individuals and Response to Teriparatide Therapy.
AB  - Sclerostin (SOST), a glycoprotein primarily derived from osteocytes, is an
      important regulator of bone remodeling. Osteogenesis imperfecta (OI) is a
      heritable disorder of bone characterized by low bone mass, bone fragility,
      recurrent fractures, and bone deformities. Altered SOST-mediated signaling may
      have a role in pathogenesis of type I collagen-related OI; however, this has not
      been evaluated in humans. We measured serum SOST levels in adults with OI who
      were enrolled in a randomized, placebo-controlled clinical trial that evaluated
      the effects of osteoanabolic therapy with teriparatide. Compared with age- and
      sex-matched control participants, mean SOST levels were lower in those with type
      I or types III/VI OI (p < 0.0001). Receiver operating curve analysis revealed
      that sclerostin alone or sclerostin plus bone mineral content discriminated
      patients with OI from controls (area under the curve 0.80 and 0.87,
      respectively). SOST levels increased in the group of patients with type I OI
      during therapy with teriparatide (compared with placebo, p = 0.01). The increase
      was significant at 6, 12, and 24 months of therapy (p <= 0.02) and was apparent
      as early as 3 months (p = 0.06). The magnitude of increases in SOST levels during
      therapy was inversely correlated with increases in vertebral volumetric bone
      mineral density (vBMD). Overall, these results suggest that: 1) SOST regulation
      is fundamentally altered in osteogenesis imperfecta; 2) serum SOST levels could
      be a biomarker of OI in adults; and 3) alterations in SOST may help predict the
      response to anabolic therapies in OI. (c) 2017 American Society for Bone and
      Mineral Research.

PMID- 29044726
TI  - A New Design Strategy for Efficient Thermally Activated Delayed Fluorescence
      Organic Emitters: From Twisted to Planar Structures.
AB  - In the traditional molecular design of thermally activated delayed fluorescence
      (TADF) emitters composed of electron-donor and electron-acceptor moieties,
      achieving a small singlet-triplet energy gap (DeltaEST ) in strongly twisted
      structures usually translates into a small fluorescence oscillator strength,
      which can significantly decrease the emission quantum yield and limit efficiency
      in organic light-emitting diode devices. Here, based on the results of quantum
      chemical calculations on TADF emitters composed of carbazole donor and 2,4,6
      triphenyl-1,3,5-triazine acceptor moieties, a new strategy is proposed for the
      molecular design of efficient TADF emitters that combine a small DeltaEST with a
      large fluorescence oscillator strength. Since this strategy goes beyond the
      traditional framework of structurally twisted, charge-transfer type emitters,
      importantly, it opens the way for coplanar molecules to be efficient TADF
      emitters. Here, a new emitter, composed of azatriangulene and diphenyltriazine
      moieties, is theoretically designed, which is coplanar due to intramolecular H
      bonding interactions. The synthesis of this hexamethylazatriangulene-triazine
      (HMAT-TRZ) emitter and its preliminary photophysical characterizations point to
      HMAT-TRZ as a potential efficient TADF emitter.

PMID- 29044727
TI  - Mutations in the highly conserved 1A rod domain of keratin 9 responsible for
      epidermolytic palmoplantar keratoderma in four Chinese families.

PMID- 29044724
TI  - Tea polyphenols for the prevention of UVB-induced skin cancer.
AB  - Skin cancer is the most common type of cancer with increasing incidence rate and
      public health burden. Solar ultraviolet (UV) radiation causes an array of
      damaging cellular and molecular events that eventually lead to the development of
      skin cancer. Despite increased awareness about sun protection, the exposure rate
      remains high with less than 15% of men and 30% of women using sunscreen on a
      regular basis. Therefore, there is an imperative need for the development of
      novel preventive approaches. Skin cancer chemoprevention using phytochemicals
      either as dietary supplements or by topical applications has gained considerable
      attention due to their low toxicity, availability, and anticarcinogenic
      properties. Tea, the second most commonly consumed beverage in the world, is a
      rich source of promising phytochemicals known as polyphenols. In this review, we
      discuss the findings of various in vitro, in vivo and human studies signifying
      the chemopreventive effects of tea polyphenols against UVB-induced skin cancer.
      This is accomplished by exploring the role of tea polyphenols in DNA repair,
      inflammation, oxidative stress, signaling pathways, and epigenetics. Finally,
      this review discusses a variety of innovative delivery methods that enhance the
      photochemopreventive effects of tea polyphenols against skin cancer.

PMID- 29044729
TI  - Outcome comparison of liver transplantation for hepatitis A-related versus
      hepatitis B-related acute liver failure in adult recipients.
AB  - Hepatitis A virus (HAV) can cause acute liver failure (ALF). This study compares
      outcomes between liver transplantation (LT) for HAV-related ALF (HAV-ALF) and LT
      for hepatitis B virus (HBV)-related ALF (HBV-ALF). Of 3616 adult LTs performed
      between January 2005 and December 2014, we performed LT for HAV-ALF recipients (n
      = 29) and LT for HBV-ALF recipients (n = 34). HAV-ALF group included 18 males and
      11 females with mean age of 33.1 years. Graft survival rates in HAV-ALF and HBV
      ALF were 65.5% and 88.0% (1 year) and 65.5% and 84.0% (5 years) (P = .048).
      Patient survival rates in HAV-ALF and HBV-ALF were 69.0% and 88.0% (1 year) and
      69.0% and 84.0% (5 years) (P = .09). Multivariate analyses demonstrated that
      acute pancreatitis and HAV recurrence were independent risk factors of graft and
      patient survival. Post-transplant outcome was poorer in patients with HAV-ALF
      than in those with HBV-ALF. This weakens LT's appropriateness in HAV-ALF patients
      with pancreatitis. HAV recurrence after LT for HAV-ALF is common and often fatal;
      thus, HAV recurrence should be monitored vigilantly, beginning early post
      transplant.

PMID- 29044730
TI  - New Challenges in Psycho-Oncology Research IV: Cognition and cancer: Conceptual
      and methodological issues and future directions.

PMID- 29044731
TI  - Nicotinamide for prevention of nonmelanoma skin cancers: a change in practice?

PMID- 29044732
TI  - Fresh tissue parathyroid allotransplantation with short-term immunosuppression: 1
      year follow-up.
AB  - BACKGROUND: Permanent hypoparathyroidism is a serious problem and requires
      medications indefinitely. Parathyroid allotransplantation (PA) with short-term
      immunosuppression is definitive choice but long-term results are not clear.
      METHOD: We performed PA from two donors to two recipients. Both recipients were
      39-year-old females. Donors were a 32-year-old female and a 36-year-old male, who
      both have chronic kidney disease. Routine tests, viral markers, and cross-matches
      were analyzed individually. The parathyroid glands were resected from the living
      donors, fragmented quickly in the operation room and injected into the left
      deltoid muscles of the two recipients. RESULTS: Methylprednisolone was
      administered on post-PA day one and two. Recipients were discharged from the
      hospital without complications. Calcium and PTH levels were observed throughout 1
      year. We did not observe any complications during the follow-up period.
      Medications ceased in post-transplantation week 1 for Case 1 and after 1 month
      for Case 2. CONCLUSION: Fresh tissue PA with short-term immunosuppression appears
      to be a promising technique that is easy to perform, is cost-effective, has low
      risk of side effects and minimal complications with compatibility for HLA
      conditions. A longer follow-up period and more case studies are needed to
      determine the risks and benefits of this procedure for future cases.

PMID- 29044728
TI  - Comparison of NMR and crystal structures of membrane proteins and computational
      refinement to improve model quality.
AB  - Membrane proteins are challenging to study and restraints for structure
      determination are typically sparse or of low resolution because the membrane
      environment that surrounds them leads to a variety of experimental challenges.
      When membrane protein structures are determined by different techniques in
      different environments, a natural question is "which structure is most
      biologically relevant?" Towards answering this question, we compiled a dataset of
      membrane proteins with known structures determined by both solution NMR and X-ray
      crystallography. By investigating differences between the structures, we found
      that RMSDs between crystal and NMR structures are below 5 A in the membrane
      region, NMR ensembles have a higher convergence in the membrane region, crystal
      structures typically have a straighter transmembrane region, have higher stereo
      chemical correctness, and are more tightly packed. After quantifying these
      differences, we used high-resolution refinement of the NMR structures to mitigate
      them, which paves the way for identifying and improving the structural quality of
      membrane proteins.

PMID- 29044733
TI  - Shyness, Preference for Solitude, and Adolescent Internalizing: The Roles of
      Maternal, Paternal, and Best-Friend Support.
AB  - The researchers examined differential outcomes related to two distinct
      motivations for withdrawal (preference for solitude and shyness) as well as the
      possibility that support from important others (mothers, fathers, and best
      friends) attenuate any such links. Adolescents (159 males, 171 females) reported
      on their motivations to withdraw, internalizing symptoms, and relationship
      quality in eighth grade, as well as their anxiety and depression in ninth grade.
      Using structural equation modeling, the authors found that maternal support
      weakened the association between shyness and internalizing problems; friend
      support weakened the association between preference for solitude and depression;
      and friend support strengthened the association between shyness and depression.
      Results suggest that shy adolescents may not derive the same benefits from
      supportive friendships as their typical peers.

PMID- 29044734
TI  - Association of androgen receptor gene CAG and GGN repeat polymorphism with
      cryptorchidism: A meta-analysis.
AB  - Researches on association between variations in the androgen receptor (AR) gene
      repeat polymorphisms and cryptorchidism (CO) had conflicting results. The aim of
      this meta-analysis was to analyse the potential effects of AR CAG and/or GGN
      repeat polymorphism on CO. Studies were independently appraised by two
      investigators on PubMed, Web of Science, EBSCO databases and Foreign Medical
      Retrieval System. Case-control studies with measurement of CAG and/or GGN repeat
      length were included. Weighted mean difference (WMD) and 95% confidence intervals
      (CIs) for the CAG or GGN repeat polymorphism and CO were calculated. Five reports
      were included in this analysis. Overall, no difference was identified between
      patients and fertile men in CAG repeat length. However, when the CO was divided
      into unilateral and bilateral, longer CAG repeat region was significantly
      associated with CO in bilateral group (WMD = 0.74; 95% CI, 0.01-1.47; p < .05).
      In addition, GGN lengths were significantly higher in patients compared with
      those in controls (WMD = 1.17; 95% CI, 0.28-2.06; p < .05). No obvious effect was
      found in the GGN length when compared unilateral or bilateral group with control
      respectively. The results in this meta-analysis indicated that AR CAG and GGN
      repeat polymorphisms may be an important pathogenesis of CO.

PMID- 29044735
TI  - Making fair comparisons in pregnancy medication safety studies: An overview of
      advanced methods for confounding control.
AB  - Understanding the safety of medication use during pregnancy relies on
      observational studies: However, confounding in observational studies poses a
      threat to the validity of estimates obtained from observational data. Newer
      methods, such as marginal structural models and propensity calibration, have
      emerged to deal with complex confounding problems, but these methods have seen
      limited uptake in the pregnancy medication literature. In this article, we
      provide an overview of newer advanced methods for confounding control and show
      how these methods are relevant for pregnancy medication safety studies.

PMID- 29044736
TI  - Multiscale Humidity Visualization by Environmentally Sensitive Fluorescent
      Molecular Rotors.
AB  - Building humidity sensors possessing the features of diverse-configuration
      compatibility, and capability of measurement of spatial and temporal humidity
      gradients is of great interest for highly integrated electronics and wearable
      monitoring systems. Herein, a visual sensing approach based on fluorescent
      imaging is presented, by assembling aggregation-induced-emission (AIE)-active
      molecular rotors into a moisture-captured network; the resulting AIE humidity
      sensors are compatible with diverse applications, having tunable geometries and
      desirable architectures. The invisible information of relative humidity (RH) is
      transformed into different fluorescence colors that enable direct observation by
      the naked eyes based on the twisted intramolecular charge-transfer effect of the
      AIE-active molecular rotors. The resulting AIE humidity sensors show excellent
      performance in terms of good sensitivity, precise quantitative measurement, high
      spatial-temporal resolution, and fast response/recovery time. Their multiscale
      applications, such as regional environmental RH detection, internal humidity
      mapping, and sensitive human-body humidity sensing are demonstrated. The proposed
      humidity visualization strategy may provide a new insight to develop humidity
      sensors for various applications.

PMID- 29044737
TI  - Chronic BMY7378 treatment alters behavioral circadian rhythms.
AB  - The mammalian circadian clock is synchronized to the day : night cycle by light.
      Serotonin modulates the circadian effects of light, with agonists inhibiting
      response to light and antagonists enhancing responses to light. A special class
      of serotonergic compounds, the mixed 5-HT1A agonist/antagonists, potentiates
      light-induced phase advances by up to 400% when administered acutely. In this
      study, we examine the effects of one of these mixed 5-HT1A agonist/antagonists,
      BMY7378, when administered chronically. Thirty adult male hamsters were
      administered either vehicle or BMY7378 via surgically implanted osmotic mini
      pumps over a period of 28 days. In a light : dark cycle, chronic BMY7378 advanced
      the phase angle of entrainment, prolonged the duration of the active phase and
      attenuated the amplitude of the wheel-running rhythm during the early night. In
      constant darkness, chronic treatment with BMY7378 significantly attenuated light
      induced phase advances, but had no significant effect on light-induced phase
      delays. Non-photic phase shifts to daytime administration of a 5-HT1A/7 agonist
      were also attenuated by chronic BMY7378 treatment. qRT-PCR analysis revealed that
      chronic BMY7378 treatment upregulated mRNA for 5-HT1A and 5-HT1B receptors in the
      hypothalamus and downregulated mRNA for 5-HT1A and monoamine oxidase-A in the
      brainstem. These results highlight adaptive changes of serotonin receptors in the
      brain to chronic treatment with BMY7378 and link such up- and downregulation to
      changes in important circadian parameters. Such long-term changes to the
      circadian system should be considered when patients are treated chronically with
      drugs that alter serotonergic function.

PMID- 29044738
TI  - Overview of mechanisms of antibiotic resistance in Pseudomonas aeruginosa: an
      ocular perspective.
AB  - Treatment of Pseudomonas aeruginosa eye infections often becomes a challenge due
      to the ability of this bacterium to be resistant to antibiotics via intrinsic and
      acquired mechanisms. Transfer of resistance due to interchangeable genetic
      elements is an important mechanism for the rapid transfer of antibiotic
      resistance in this pathogen. As a result, drug-resistant strains are becoming
      increasingly prevalent worldwide. This review systematically analyses data from
      recent publications to describe the global prevalence and antibiotic sensitivity
      of ocular P. aeruginosa. Thirty-seven studies were selected for review from
      PubMed-based searches using the criteria 'microbial keratitis OR eye infection
      AND Pseudomonas aeruginosa AND antibiotic resistance' and limiting to papers from
      2011 onward, to demonstrate the antibiotic resistance from isolates from around
      the world. Subsequently, we reviewed the ways in which P. aeruginosa can become
      resistant to antibiotics. Both the rate of isolation of bacteria in general (79
      per cent of cases), and prevalence of P. aeruginosa (68 per cent of all isolates)
      were highest in contact lens-related microbial keratitis. The average resistance
      rate to common ocular antibiotics such as ciprofloxacin (9 per cent), gentamicin
      (22 per cent) and ceftazidime (13 per cent) remained relatively low. However,
      there were large variations in resistance rates reported in studies from
      different countries, for example resistance to ciprofloxacin reached up to 33 per
      cent. We next reviewed the types of mobile genetic elements (MGEs) such as
      plasmids, integrons and transposons that are frequently associated with drug
      resistance in P. aeruginosa. MGEs are important for the transmission of
      resistance to beta-lactams and aminoglycosides and recently have been shown to be
      potential factors for the transmission of fluoroquinolone resistance. Studies on
      the molecular mechanisms of resistance transfer in ocular P. aeruginosa have
      begun to be reported and will provide valuable information on the emergence of
      new antibiotic resistance and potential to treat resistant strains.

PMID- 29044739
TI  - Peripheral Intravenous Cannula Insertion and Use in the Emergency Department: An
      Intervention Study.
AB  - OBJECTIVES: The objective was to examine cannulation practice and effectiveness
      of a multimodal intervention to reduce peripheral intravenous cannula (PIVC)
      insertion in emergency department (ED) patients. METHODS: A prospective before
      and after study and cost analysis was conducted at a single tertiary ED in
      Australia. Data were collected 24 hours a day for 2 weeks pre- and post
      implementation of a multimodal intervention. PIVC placement and utilization
      within 24 hours were evaluated in all eligible patients. RESULTS: A total of
      4,173 participants were included in the analysis. PIVCs were placed in 42.1% of
      patients' pre intervention and 32.4% post intervention, a reduction of 9.8% (95%
      confidence interval [CI] = 6.8 to -12.72%). PIVC usage within 24 hours of
      admission was 70.5% pre intervention and 83.4% post intervention, an increase of
      12.9% (95% CI = 8.8% to 17.0%). Sixty-six patients were observed in the ED for
      cost analysis. The mean time per PIVC insertion was 15.3 (95% CI = 12.6 to 17.9)
      minutes. PIVC insertion cost, including staff time and consumables per
      participant, was A$22.79 (95% CI = A$19.35 to A$26.23). CONCLUSIONS: The
      intervention reduced PIVC placement in the ED and increased the percentage of
      PIVCs placed that were used. This program benefits patients and health services
      alike, with potential for large cost savings.

PMID- 29044740
TI  - Highly Efficient Ternary-Blend Polymer Solar Cells Enabled by a Nonfullerene
      Acceptor and Two Polymer Donors with a Broad Composition Tolerance.
AB  - In this work, highly efficient ternary-blend organic solar cells (TB-OSCs) are
      reported based on a low-bandgap copolymer of PTB7-Th, a medium-bandgap copolymer
      of PBDB-T, and a wide-bandgap small molecule of SFBRCN. The ternary-blend layer
      exhibits a good complementary absorption in the range of 300-800 nm, in which
      PTB7-Th and PBDB-T have excellent miscibility with each other and a desirable
      phase separation with SFBRCN. In such devices, there exist multiple energy
      transfer pathways from PBDB-T to PTB7-Th, and from SFBRCN to the above two
      polymer donors. The hole-back transfer from PTB7-Th to PBDB-T and multiple
      electron transfers between the acceptor and the donor materials are also observed
      for elevating the whole device performance. After systematically optimizing the
      weight ratio of PBDB-T:PTB7-Th:SFBRCN, a champion power conversion efficiency
      (PCE) of 12.27% is finally achieved with an open-circuit voltage (Voc ) of 0.93
      V, a short-circuit current density (Jsc ) of 17.86 mA cm-2 , and a fill factor of
      73.9%, which is the highest value for the ternary OSCs reported so far.
      Importantly, the TB-OSCs exhibit a broad composition tolerance with a high PCE
      over 10% throughout the whole blend ratios.

PMID- 29044741
TI  - Planar-Structure Perovskite Solar Cells with Efficiency beyond 21.
AB  - Low temperature solution processed planar-structure perovskite solar cells gain
      great attention recently, while their power conversions are still lower than that
      of high temperature mesoporous counterpart. Previous reports are mainly focused
      on perovskite morphology control and interface engineering to improve
      performance. Here, this study systematically investigates the effect of precise
      stoichiometry, especially the PbI2 contents on device performance including
      efficiency, hysteresis and stability. This study finds that a moderate residual
      of PbI2 can deliver stable and high efficiency of solar cells without hysteresis,
      while too much residual PbI2 will lead to serious hysteresis and poor transit
      stability. Solar cells with the efficiencies of 21.6% in small size (0.0737 cm2 )
      and 20.1% in large size (1 cm2 ) with moderate residual PbI2 in perovskite layer
      are obtained. The certificated efficiency for small size shows the efficiency of
      20.9%, which is the highest efficiency ever recorded in planar-structure
      perovskite solar cells, showing the planar-structure perovskite solar cells are
      very promising.

PMID- 29044742
TI  - Influence of the pericellular and extracellular matrix structural properties on
      chondrocyte mechanics.
AB  - Understanding the mechanical factors that drive the biological responses of
      chondrocytes is central to our interpretation of the cascade of events that lead
      to osteoarthritic changes in articular cartilage. Chondrocyte mechanics is
      complicated by changes in tissue properties that can occur as osteoarthritis (OA)
      progresses and by the interaction between macro-scale, tissue level, properties,
      and micro-scale pericellular matrix (PCM) and local extracellular matrix (ECM)
      properties, both of which cannot be easily studied using in vitro systems. Our
      objective was to study the influence of macro- and micro-scale OA-associated
      structural changes on chondrocyte strains. We developed a multi-scale finite
      element model of articular cartilage subjected to unconfined loading, for the
      following three conditions: (i) normal articular cartilage, (ii) OA cartilage
      (where macro and micro-scale changes in collagen content, matrix modulus, and
      permeability were modeled), and (iii) early-stage OA cartilage (where only micro
      scale changes in matrix modulus were modeled). In the macro-scale model, we found
      that a depth-dependent strain field was induced in both healthy and OA cartilage
      and that the middle and superficial zones of OA cartilage had increased tensile
      and compressive strains. At the micro-scale, chondrocyte shear strains were
      sensitive to PCM and local ECM properties. In the early-OA model, micro-scale
      spatial softening of PCM and ECM resulted in a substantial increase (30%) of
      chondrocyte shear strain, even with no structural changes in macro-scale tissue
      properties. Our study provides evidence that micromechanical changes at the
      cellular level may affect chondrocyte activities before macro-scale degradations
      at the tissue level become apparent. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:721-729, 2018.

PMID- 29044743
TI  - Variation in the SSUrDNA of the Genus Protostelium Leads to a New Phylogenetic
      Understanding of the Genus and of the Species Concept for Protostelium mycophaga
      (Protosteliida, Amoebozoa).
AB  - Members of the genus Protostelium (including P. mycophaga, P. nocturnum, and P.
      okumukumu) are protosteloid amoebae commonly found in terrestrial habitats on
      dead plant matter. They, along with the closely allied nominal genus
      Planoprotostelium, containing the single species Pl. aurantium, all have an
      amoeboid trophic stage with acutely pointed subpseudopodia and orange lipid
      droplets in the granuloplasm. These amoebae form stalked fruiting bodies topped
      with a single, usually deciduous spore. The species are identified based on their
      fruiting body morphologies except for Pl. aurantium which looks similar to P.
      mycophaga in fruiting morphology, but has amoebae that can make flagella in
      liquid medium. We built phylogenetic trees using nuclear small subunit ribosomal
      DNA sequences of 35 isolates from the genera Protostelium and Planoprotostelium
      and found that (1) the nonflagellated P. nocturnum and P. okumukumu branch
      basally in the genus Protostelium, (2) the flagellate, Pl. aurantium falls within
      the genus Protostelium in a monophyletic clade with the nominal variety, P.
      mycophaga var. crassipes, (3) the cultures initially identified as Protostelium
      mycophaga can be divided into at least three morphologically recognizable taxa,
      P. aurantium n. comb., P. apiculatum n. sp., and P. m. rodmani n. subsp., as well
      as a paraphyletic assemblage that includes the remainder of the P. mycophaga
      morphotype. These findings have implications for understanding the ecology,
      evolution, and diversity of these amoeboid organisms and for using these amoebae
      as models for other amoeboid groups.

PMID- 29044744
TI  - Ontogenetic variation in the sensory structures on the pedipalps of cosmetid
      harvestmen (Arachnida, Opiliones, Laniatores).
AB  - In arachnids, pedipalps are highly variable appendages that may be used in
      feeding, courtship, defense, and agonistic encounters. In cosmetid harvestmen,
      adults have pedipalps that feature flattened femora, spoon-shaped tibiae, and
      robust tarsal claws. In contrast, the pedipalps of nymphs are elongate with
      cylindrical podomeres and are adorned with delicate pretarsi. In this study, we
      used scanning electron microscopy to examine the distribution of cuticular
      structures (e.g., sensilla chaetica, pores) on the elements of the pedipalps of
      adults and nymphs of three species of cosmetid harvestmen. Our results indicate
      that there is considerable ontogenetic variation in the morphology of the
      trochanter, femur, patella, tibia, and tarsus. The pretarsus of the nymph has a
      ventral patch of setae that is absent from the adult tarsal claw. We observed
      this structure on all three cosmetid species as well as on the pedipalps of an
      additional seven morphospecies of nymphs collected in Belize and Costa Rica. This
      structure may represent a previously unrecognized autapomorphy for Cosmetidae.
      Examinations of the pedipalps of antepenultimate nymphs of additional
      gonyleptoidean harvestmen representing the families Ampycidae, Cranaidae,
      Manaosbiidae, and Stygnidae revealed the occurrence of unusual, plumose tarsal
      setae, but no setal patches on the tarsal claw.

PMID- 29044745
TI  - Solvent Effect on the Photoinduced Structural Change of a Phosphorescent
      Molecular Butterfly.
AB  - Photoinduced structural changes (PSC) is one of the fundamental excited-state
      dynamic processes, and yet often very challenging to distinguish from competing
      electronic excited-state relaxation channels having similar or even comparable
      timescales. Here, we report a detailed study on the PSC of a pyrazolate bridged
      platinum(II) binuclear complex, BFPtPZ (C^NPt(MU-pz')2 PtC^N, C^N=2-(2,4
      difluorophenyl)pyridine, pz'=pyrazolate), a molecular butterfly, using time
      correlated single photon counting measurements at different wavelengths and
      sample temperatures. Analysis of the results obtained using dichloromethane (DCM)
      and ethylene carbonate (EC) as solvents enabled us to reveal an unexpected,
      strong solvent effect on the PSC processes. We show that a rapid PSC process with
      a characteristic timescale of 323 ps is observed in DCM, which leads to an
      excitation equilibrium between the ligand center/metal-to-ligand charge transfer
      (3 LC/MLCT) and metal-metal-to-ligand charge transfer (3 MMLCT) triplet states.
      The subsequent relaxation from these electronic states to the ground state takes
      place in several nanoseconds. In contrast, the corresponding PSC process in EC
      appears slow at all temperatures studied in our experiments and showed no sign of
      such excitation equilibrium. The observed solvent effect is found to arise from
      distinct solvent properties including their viscosities and polarities as well as
      the peculiar electronic excited-states of the butterfly-like molecules with
      charge transfer character.

PMID- 29044746
TI  - Breaking the Concentration Barrier for Single-Molecule Fluorescence Measurements.
AB  - Fluorescence-based single-molecule techniques have become widely used tools to
      reveal dynamic processes of biomolecules and elucidate their molecular
      mechanisms. However, the concentration upper limit of labeled species that can be
      used in single-molecule fluorescence measurements is at the low nm range, which
      is below the Michaelis constants of many enzymatic reactions and physiological
      concentrations of many biomolecules. Such discrepancy limits the application of
      single-molecule fluorescence tools. Several techniques have been developed to
      break the concentration barrier. In this Concept, we focus on reviewing
      fundamental principles of these techniques and wish to inspire development of new
      and better tools to achieve this goal.

PMID- 29044747
TI  - Evidence for a [17] pi-Electronic Full-Fledged Non-innocent Gallium(III)-Corrole
      Radical.
AB  - One-electron oxidation of a GaIII -corrole with N(4-BrC6 H4 )3 SbCl6 resulted in
      an air-stable non-innocent GaIII -corrole radical. The single-crystal X-ray
      crystallography of the 2,17-bis-formyl-5,10,15-tris(pentafluorophenyl)corrolato
      gallium(III)(chloride) radical ([3-Cl]. ) revealed delocalization of the unpaired
      electron, which was further confirmed by electron spin resonance (ESR)
      spectroscopy and spin density distribution plot. In addition, the nucleus
      independent chemical shift (NICS), anisotropy-induced current density (AICD) and
      harmonic oscillator model of aromaticity (HOMA) supported a [17] pi-electron
      conjugated (or antiaromatic) radical.

PMID- 29044748
TI  - Assembly of Coordination Polymers Using Thioether-Functionalized
      Octasilsesquioxanes: Occurrence of (CuX)n Clusters (X=Br and I) within 3D-POSS
      Networks.
AB  - For the first time, POSS-based coordination polymers (CPs) have been structurally
      characterized. These CPs were obtained in high yield via self-assembly reactions
      of thioether-functionalized polysilsesquioxanes with CuI salts under mild
      conditions. Single crystal analyses revealed the formation of 3D networks
      incorporating different secondary building units (SBUs) as connection nodes. The
      nature of the -SAr functionality allows a fine-tuning of the cluster nuclearity,
      that is, butterfly-shaped Cu2 X2 or closed cubane-type Cu4 I4 cores. As such, the
      resulting hybrid materials exhibit a combination of high thermal stability
      arising from the inorganic POSS core along with interesting luminescent
      properties conferred by the cubane cluster core. Furthermore, the occurrence of
      channels has been shown crystallographically in the case of the Cu4 I4 cluster
      containing CP.

PMID- 29044749
TI  - Desymmetrization of Bisallylic Amides through Catalytic Enantioselective
      Bromocyclization with BINAP Monoxide.
AB  - We report the first desymmetrization of bisallylic amides by enantioselective
      bromocyclization with BINAP monoxide as a catalyst. Depending upon the
      substitution pattern of the alkene moieties, densely functionalized, optically
      active oxazoline or dihydrooxazine compounds were obtained in a highly
      stereoselective manner. The remaining alkene moiety was subjected to various
      functional group manipulations to afford a diverse array of chiral molecules with
      multiple stereogenic centers.

PMID- 29044750
TI  - Model Macrocyclic Ligands for Proof-of-Concept Mechanistic Studies in Transition
      Metal Catalysis.
AB  - In this Concept article, we will scrutinize different approaches devoted to the
      mechanistic understanding of catalytic processes, paying special attention to the
      successful use of triazamacrocyclic aryl-halide or arene-containing substrates
      used for Cu-, Ag-, Au-, Co- and Ni-catalysis. The importance of designing model
      substrate platforms to unravel mechanistic details at a molecular level of C-C or
      C-heteroatom bond-forming processes catalyzed by transition metals will be
      highlighted. This fundamental mechanistic knowledge will serve as a foundation
      for the catalyst design for a desired transformation.

PMID- 29044752
TI  - Zn2+ Interrupts R4-R3 Association Leading to Accelerated Aggregation of Tau
      Protein.
AB  - Direct binding of divalent metal ion, especially Zn2+ , have been shown to
      increase the rate of tau aggregation and enhance tau toxicity in cells. Hence,
      understanding the molecular basis of the Zn2+ -accelerated tau aggregation can
      potentially determine the molecular interactions modulating tau aggregation.
      Herein, we show that Zn2+ coordinates through the cysteine in R3 repeat and
      significantly accelerates the aggregation rate of the three repeat tau constructs
      (K19) but that the coordination is incapable of increasing the aggregation rate
      of the 20 amino acid peptide derived from the R3 repeat (R3) of tau. The NMR
      characterization of the binding of Zn2+ to K19, together with the aggregation
      studies with K19, R3 and R4 peptides, reveal the presence of an aggregation
      inhibitory interaction between the R3 and R4 repeat of K19. Our data show that
      binding of Zn2+ to R3 repeat of tau, weaken the aggregation-inhibiting influence
      between R3 and R4 repeats, leading to faster aggregation of tau protein.

PMID- 29044751
TI  - Simultaneous imaging of hyperpolarized [1,4-13 C2 ]fumarate, [1-13 C]pyruvate and
      18 F-FDG in a rat model of necrosis in a clinical PET/MR scanner.
AB  - A co-polarization scheme for [1,4-13 C2 ]fumarate and [1-13 C]pyruvate is
      presented to simultaneously assess necrosis and metabolism in rats with
      hyperpolarized 13 C magnetic resonance (MR). The co-polarization was performed in
      a SPINlab polarizer. In addition, the feasibility of simultaneous positron
      emission tomography (PET) and MR of small animals with a clinical PET/MR scanner
      is demonstrated. The hyperpolarized metabolic MR and PET was demonstrated in a
      rat model of necrosis. The polarization and T1 of the co-polarized [1,4-13 C2
      ]fumarate and [1-13 C]pyruvate substrates were measured in vitro and compared
      with those obtained when the substrates were polarized individually. A
      polarization of 36 +/- 4% for fumarate and 37 +/- 6% for pyruvate was obtained.
      We found no significant difference in the polarization and T1 values between the
      dual and single substrate polarization. Rats weighing about 400 g were injected
      intramuscularly in one of the hind legs with 200 MUL of turpentine to induce
      necrosis. Two hours later, 13 C metabolic maps were obtained with a chemical
      shift imaging sequence (16 * 16) with a resolution of 3.1 * 5.0 * 25.0 mm3 . The
      13 C spectroscopic images were acquired in 12 s, followed by an 8-min 18 F-2
      fluoro-2-deoxy-d-glucose (18 F-FDG) PET acquisition with a resolution of 3.5 mm.
      [1,4-13 C2 ]Malate was observed from the tissue injected with turpentine
      indicating necrosis. Normal [1-13 C]pyruvate metabolism and 18 F-FDG uptake were
      observed from the same tissue. The proposed co-polarization scheme provides a
      means to utilize multiple imaging agents simultaneously, and thus to probe
      various metabolic pathways in a single examination. Moreover, it demonstrates the
      feasibility of small animal research on a clinical PET/MR scanner for combined
      PET and hyperpolarized metabolic MR.

PMID- 29044753
TI  - Development of a quantitative intracranial vascular features extraction tool on
      3D MRA using semiautomated open-curve active contour vessel tracing.
AB  - PURPOSE: To develop a quantitative intracranial artery measurement technique to
      extract comprehensive artery features from time-of-flight MR angiography (MRA).
      METHODS: By semiautomatically tracing arteries based on an open-curve active
      contour model in a graphical user interface, 12 basic morphometric features and
      16 basic intensity features for each artery were identified. Arteries were then
      classified as one of 24 types using prediction from a probability model. Based on
      the anatomical structures, features were integrated within 34 vascular groups for
      regional features of vascular trees. Eight 3D MRA acquisitions with intracranial
      atherosclerosis were assessed to validate this technique. RESULTS: Arterial
      tracings were validated by an experienced neuroradiologist who checked agreement
      at bifurcation and stenosis locations. This technique achieved 94% sensitivity
      and 85% positive predictive values (PPV) for bifurcations, and 85% sensitivity
      and PPV for stenosis. Up to 1,456 features, such as length, volume, and averaged
      signal intensity for each artery, as well as vascular group in each of the MRA
      images, could be extracted to comprehensively reflect characteristics,
      distribution, and connectivity of arteries. Length for the M1 segment of the
      middle cerebral artery extracted by this technique was compared with reviewer
      measured results, and the intraclass correlation coefficient was 0.97.
      CONCLUSION: A semiautomated quantitative method to trace, label, and measure
      intracranial arteries from 3D-MRA was developed and validated. This technique can
      be used to facilitate quantitative intracranial vascular research, such as
      studying cerebrovascular adaptation to aging and disease conditions. Magn Reson
      Med 79:3229-3238, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29044754
TI  - Factors affecting access to daily oral and dental care among adults with
      intellectual disabilities.
AB  - BACKGROUND/PURPOSE: Accessing oral health care can be more difficult for adults
      with intellectual disabilities with reports of poorer levels of oral health. This
      investigation identifies factors influencing engagement in day-to-day oral and
      dental health care for adults with intellectual disabilities. METHOD: A survey,
      containing questions about facilitators and barriers to maintaining oral health
      and hygiene, was completed with adults with intellectual disabilities and their
      caregivers (N = 372). RESULTS: Data were analysed using thematic network
      analysis. Two global themes were identified; "Personal and lifestyle influences,"
      mentioned more often as barriers to oral care, included physical, sensory,
      cognitive, behavioural and affective factors and "social and environmental
      factors," mentioned more as facilitators, included caregiver support, equipment
      and adaptations used and oral hygiene routine. CONCLUSIONS: Numerous individual,
      social and environmental factors influence oral care. A coordinated
      organisational response is advocated involving collaboration between dental and
      intellectual disability services and training for caregivers and people with
      intellectual disabilities.

PMID- 29044755
TI  - Epoxyazadiradione Purified from the Azadirachta indica Seed Induced Mitochondrial
      Apoptosis and Inhibition of NFkappaB Nuclear Translocation in Human Cervical
      Cancer Cells.
AB  - Epoxyazadiradione (EAD) is an important limonoid present in Neem (Azadirachta
      indica) plant. In the present study, we have purified EAD from Neem seed and
      studied its anticancer potential in human cervical cancer (HeLa) cells. Cell
      proliferation inhibition studies indicated that the GI50 value of EAD is 7.5 +/-
      0.0092 MUM in HeLa cells, whereas up to 50 MUM concentrations EAD did not affect
      the growth of normal H9C2 cells. The control drug cisplatin inhibited the growth
      of both HeLa and H9C2 cells with a GI50 value of 2.92 +/- 1.192 and 4.22 +/-
      1.568 MUM, respectively. Nuclear DNA fragmentation, cell membrane blebbing,
      phosphatidylserine translocation, upregulation of Bax, caspase 3 activity and
      poly (ADP ribose) polymerase cleavage and downregulation of BCl2 in HeLa cells on
      treatment with EAD indicated the apoptotic cell death. Increase in caspase 9
      activity and release of active cytochrome c to the cytoplasm on treatment with
      EAD confirmed that the apoptosis was mediated through the mitochondrial pathway.
      Epoxyazadiradione also inhibited the nuclear translocation of nuclear factor
      kappaB in HeLa cells. Thus, our studies demonstrated EAD as a potent and safe
      chemotherapeutic agent when compared with the standard drug cisplatin that is
      toxic to both cancer and normal cells equally. Copyright (c) 2017 John Wiley &
      Sons, Ltd.

PMID- 29044756
TI  - Static Electricity-Responsive Supramolecular Assembly.
AB  - Stimuli-responsive materials can convert between molecular scale and macroscopic
      scale phenomena. Two macroscopic static electricity-responsive phenomena based on
      nanoscale supramolecular assemblies of a zinc porphyrin derivative are presented.
      One example involves the movement of supramolecular assemblies in response to
      static electricity. The assembly of a pyridine (Py) complex of the above
      mentioned derivative in cyclohexane is drawn to a positively charged material,
      whereas the assembly of a 3,5-dimethylpyridine complex is drawn to a negatively
      charged material. The second phenomenon involves the movement of a non-polar
      solvent in response to static electrical stimulation. A cyclohexane solution
      containing a small quantity of the Py-complexed assembly exhibited a strong
      movement response towards negatively charged materials. Based on spectroscopic
      measurements and electron microscope observations, it was revealed that the
      assembled formation generates the observed response to static electricity.

PMID- 29044757
TI  - Synthesis and Photophysical Characterization of 2,3-Dihydroquinolin-4-imines: New
      Fluorophores with Color-Tailored Emission.
AB  - In this study, a series of variously substituted 2,3-dihydroquinolin-4-imines
      (DQIs) were synthesized from N-substituted propargylanilines by copper(I)
      catalyzed annulation. The approach adopted in this study under mild, effective
      conditions exhibited broad substrate tolerance, particularly for functional
      groups substituted on anilines. Most of the DQI derivatives synthesized under
      optimal conditions were obtained in good isolated yields of 63-88 %. 2,3
      Dihydroquinolinimine thus obtained was easily converted to important structures
      like 2,3-dihydroquinolone and tetrahydrobenzodiazepin-5-one, confirming the
      importance of this strategy in constructing various heterocycles. Surprisingly,
      2,3-dihydroquinolinimines thus obtained exhibited bright fluorescence with
      quantum yields up to 66 %. The density functional theory (DFT) and time-dependent
      DFT (TD-DFT) calculations were performed for understanding the excited-state
      nature of DQI system. Accordingly, a tailored DQI derivative bearing methoxy
      group at C-6 position and acetoxy group at C-7 position was designed and
      synthesized to give emission at 559 nm with redshift compared to the 7-methoxy
      substituted DQI. A detailed study of DQI structures with their photophysical
      properties was performed with five control molecules and consequently
      demonstrated the uniqueness of the chemical structures of DQIs.

PMID- 29044758
TI  - Teamwork and conflicts in paediatric end-of-life care.

PMID- 29044759
TI  - Liver transplant length of stay (LOS) index: A novel predictive score for
      hospital length of stay following liver transplantation.
AB  - An index to predict hospital length of stay after liver transplantation could
      address unmet clinical needs. Length of stay is an important surrogate for
      hospital costs and efforts to limit stays can preserve our healthcare resources.
      Here, we devised a scoring system that predicts hospital length of stay following
      liver transplantation. We used univariate and multivariate analyses on 73 635
      adult liver transplant recipient data and identified independent recipient and
      donor risk factors for prolonged hospital stay (>30 days). Multiple imputation
      was used to account for missing variables. We identified 22 factors as
      significant predictors of prolonged hospital stay, including the most significant
      risk factors: intensive care unit (ICU) admission (OR 1.75, CI 1.58-1.95) and
      previous transplant (OR 1.60, CI 1.47-1.75). The length of stay (LOS) index
      assigns weighted risk points to each significant factor in a scoring system to
      predict prolonged hospital stay after liver transplantation with a c-statistic of
      0.75. The LOS index demonstrated good discrimination across the entire
      population, dividing the cohort into tertiles, which had odds ratios of 2.25 (CI
      2.06-2.46) and 7.90 (7.29-8.56) for prolonged hospital stay (>30 days). The LOS
      index utilizes 22 significant donor and recipient factors to accurately predict
      hospital length of stay following liver transplantation. The index further
      demonstrates the basis for a clear clinical recommendation to mitigate risk of
      long hospitalization by minimizing cold ischemia time.

PMID- 29044760
TI  - Development of novel and non-invasive diagnostic markers for lower urinary tract
      symptoms using urothelial cells in voided urine.
AB  - OBJECTIVES: We evaluated the association between lower urinary tract symptoms
      (LUTS) and the expression of connexin (Cx) and transient receptor potential (TRP)
      channel on urothelial cells non-invasively collected from voided urine in humans.
      METHODS: A total of 55 patients (36 males and 19 females, median age: 71 years
      old), who were followed up at University of Yamanashi Hospital, were enrolled in
      the present study. Urothelial cells were collected from voided urine of patients,
      and the mRNA expression of each subtype of Cxs and TRP channels was measured
      using quantitive real-time reverse transcription polymerase chain reaction. We
      then analyzed the correlation between the expression of Cxs and TRP channels and
      symptom scores in International Prostate Symptom Scoreand Overactive Bladder
      Symptom Score, in addition to Interstitial Cystitis Symptom Index (ICSI) from
      only interstitial cystitis (IC) patients. RESULTS: Non-adjusted statistical
      procedure using Spearman's rank-correlation showed that there were significant
      correlations between the following expressions and symptom scores; (positive
      correlations) Cx26 versus urgency score, Cx40 versus nocturia, TRPM2 versus
      intermittency, TRPV1 versus urge incontinence, (negative correlation) Cx40 versus
      intermittency, TRPM7 versus pollakisuria. However, a multiple comparison
      adjustment using Bonferroni correction showed that only Cx40 had a trend of
      correlation with nocturia in ICSI. CONCLUSIONS: The expressions of Cxs and TRP
      channels on urothelial cells in voided urine could be related to LUTS. Further
      analysis of urothelial cells in voided urine has the potential to reveal the
      mechanism of the LUTS and develop new markers with non-invasive methods.

PMID- 29044761
TI  - Thermal refugia against coral bleaching throughout the northern Red Sea.
AB  - Tropical reefs have been impacted by thermal anomalies caused by global warming
      that induced coral bleaching and mortality events globally. However, there have
      only been very few recordings of bleaching within the Red Sea despite covering a
      latitudinal range of 15 degrees  and consequently it has been considered a region
      that is less sensitive to thermal anomalies. We therefore examined historical
      patterns of sea surface temperature (SST) and associated anomalies (1982-2012)
      and compared warming trends with a unique compilation of corresponding coral
      bleaching records from throughout the region. These data indicated that the
      northern Red Sea has not experienced mass bleaching despite intensive Degree
      Heating Weeks (DHW) of >15 degrees C-weeks. Severe bleaching was restricted to
      the central and southern Red Sea where DHWs have been more frequent, but far less
      intense (DHWs <4 degrees C-weeks). A similar pattern was observed during the 2015
      2016 El Nino event during which time corals in the northern Red Sea did not
      bleach despite high thermal stress (i.e. DHWs >8 degrees C-weeks), and bleaching
      was restricted to the central and southern Red Sea despite the lower thermal
      stress (DHWs < 8 degrees C-weeks). Heat stress assays carried out in the northern
      (Hurghada) and central (Thuwal) Red Sea on four key reef-building species
      confirmed different regional thermal susceptibility, and that central Red Sea
      corals are more sensitive to thermal anomalies as compared to those from the
      north. Together, our data demonstrate that corals in the northern Red Sea have a
      much higher heat tolerance than their prevailing temperature regime would
      suggest. In contrast, corals from the central Red Sea are close to their thermal
      limits, which closely match the maximum annual water temperatures. The northern
      Red Sea harbours reef-building corals that live well below their bleaching
      thresholds and thus we propose that the region represents a thermal refuge of
      global importance.

PMID- 29044762
TI  - Density-weighted concentric rings k-space trajectory for 1 H magnetic resonance
      spectroscopic imaging at 7 T.
AB  - It has been shown that density-weighted (DW) k-space sampling with spiral and
      conventional phase encoding trajectories reduces spatial side lobes in magnetic
      resonance spectroscopic imaging (MRSI). In this study, we propose a new
      concentric ring trajectory (CRT) for DW-MRSI that samples k-space with a density
      that is proportional to a spatial, isotropic Hanning window. The properties of
      two different DW-CRTs were compared against a radially equidistant (RE) CRT and
      an echo-planar spectroscopic imaging (EPSI) trajectory in simulations, phantoms
      and in vivo experiments. These experiments, conducted at 7 T with a fixed nominal
      voxel size and matched acquisition times, revealed that the two DW-CRT designs
      improved the shape of the spatial response function by suppressing side lobes,
      also resulting in improved signal-to-noise ratio (SNR). High-quality spectra were
      acquired for all trajectories from a specific region of interest in the motor
      cortex with an in-plane resolution of 7.5 * 7.5 mm2 in 8 min 3 s. Due to hardware
      limitations, high-spatial-resolution spectra with an in-plane resolution of 5 * 5
      mm2 and an acquisition time of 12 min 48 s were acquired only for the RE and one
      of the DW-CRT trajectories and not for EPSI. For all phantom and in vivo
      experiments, DW-CRTs resulted in the highest SNR. The achieved in vivo spectral
      quality of the DW-CRT method allowed for reliable metabolic mapping of eight
      metabolites including N-acetylaspartylglutamate, gamma-aminobutyric acid and
      glutathione with Cramer-Rao lower bounds below 50%, using an LCModel analysis.
      Finally, high-quality metabolic mapping of a whole brain slice using DW-CRT was
      achieved with a high in-plane resolution of 5 * 5 mm2 in a healthy subject. These
      findings demonstrate that our DW-CRT MRSI technique can perform robustly on MRI
      systems and within a clinically feasible acquisition time.

PMID- 29044763
TI  - Theta band oscillations reflect more than entrainment: behavioral and neural
      evidence demonstrates an active chunking process.
AB  - Parsing continuous acoustic streams into perceptual units is fundamental to
      auditory perception. Previous studies have uncovered a cortical entrainment
      mechanism in the delta and theta bands (~1-8 Hz) that correlates with formation
      of perceptual units in speech, music, and other quasi-rhythmic stimuli. Whether
      cortical oscillations in the delta-theta bands are passively entrained by regular
      acoustic patterns or play an active role in parsing the acoustic stream is
      debated. Here, we investigate cortical oscillations using novel stimuli with 1/f
      modulation spectra. These 1/f signals have no rhythmic structure but contain
      information over many timescales because of their broadband modulation
      characteristics. We chose 1/f modulation spectra with varying exponents of f,
      which simulate the dynamics of environmental noise, speech, vocalizations, and
      music. While undergoing magnetoencephalography (MEG) recording, participants
      listened to 1/f stimuli and detected embedded target tones. Tone detection
      performance varied across stimuli of different exponents and can be explained by
      local signal-to-noise ratio computed using a temporal window around 200 ms.
      Furthermore, theta band oscillations, surprisingly, were observed for all
      stimuli, but robust phase coherence was preferentially displayed by stimuli with
      exponents 1 and 1.5. We constructed an auditory processing model to quantify
      acoustic information on various timescales and correlated the model outputs with
      the neural results. We show that cortical oscillations reflect a chunking of
      segments, > 200 ms. These results suggest an active auditory segmentation
      mechanism, complementary to entrainment, operating on a timescale of ~200 ms to
      organize acoustic information.

PMID- 29044764
TI  - Estimated glomerular filtration rate and the risk-benefit profile of intensive
      blood pressure control amongst nondiabetic patients: a post hoc analysis of a
      randomized clinical trial.
AB  - BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT;
      ClinicalTrials.gov, NCT01206062) reported reduced cardiovascular events by
      intensive blood pressure (BP) control amongst hypertensive patients without
      diabetes. However, the risk-benefit profile of intensive BP control may differ
      across estimated glomerular filtration rate (eGFR) levels. METHODS: This is a
      post hoc analysis of the SPRINT. Nondiabetic hypertensive adults (n = 9361) with
      eGFR >20 mL per min per 1.73 m2 were enrolled from 102 US facilities between
      November 2010 and March 2013 and were followed up until August 2015 (median
      follow-up, 3.26 years). Patients were randomly assigned to either a systolic BP
      target of <120 or <140 mmHg (for intensive or standard treatment, respectively).
      The outcomes of interests were the development of (i) fatal and nonfatal major
      cardiovascular events and (ii) acute kidney injury (AKI). RESULTS: The
      cardiovascular benefit from intensive treatment was attenuated with lower eGFR
      (Pinteraction  = 0.019), whereas eGFR did not modify the adverse effect on AKI
      (Pinteraction  = 0.179). Amongst 891 participants with eGFR <45 mL per min per
      1.73 m2 , intensive treatment did not reduce the cardiovascular outcome (54/446
      vs. 54/445 events in the standard group, respectively; hazard ratio [HR], 0.92;
      95% CI, 0.62-1.38) with an absolute rate difference (ARD) of -0.02 (95% CI, -0.07
      to +0.03) per 100 patient-years, whereas it increased AKI (62/446 vs. 38/445
      events in the standard group; HR, 1.73; 95% CI, 1.12-2.66) with an ARD of +1.93
      (95% CI, +1.88 to +1.97) per 100 patient-years. CONCLUSIONS: Intensive BP control
      may provide little or no benefit and even be harmful for patients with moderate
      to-advanced chronic kidney disease.

PMID- 29044766
TI  - Do men and women with intellectual disabilities understand death?
AB  - BACKGROUND: Individuals with ID are often withheld information about the death of
      their loved ones as it has often been thought that they do not understand death
      or cannot grieve. This grief exacerbates the stress of individuals with ID as
      they often encounter secondary losses such as transitioning to a care facility.
      The aim of this study is to investigate men and women with ID understanding death
      concepts and to what extent. METHOD: Adopting a stratified random sampling
      method, 156 Chinese people with ID were invited to join the study. One hundred
      and ten participants were interviewed using simple death related vignettes
      expanding upon and replicating a published study carried out in Ireland. The
      understanding of the five death concepts: causality, irreversibility,
      nonfunctionality, universality and inevitability was examined. The correlates of
      demographics, bereavement experiences and comprehension were explored. RESULTS:
      The majority of the participants did understand concepts such as death is
      irreversible and that the deceased no longer function. One third of the
      participants understood causality and the universality of death. One fifth
      understood the inevitability of death. Previous bereavement experiences were
      correlated with higher understanding. Communication and community skills were
      correlated with all concepts of death except universality. CONCLUSION: The
      results indicate that individuals with ID do have a partial to full understanding
      of the concepts of death. The culture of Hong Kong is one that considers death to
      be a taboo or unlucky subject. Therefore, the results mirror the the lack of
      understanding of universality and inevitability concepts as it is forbidden to
      speak of these concepts. An open and honest environment is encouraged to educate
      individuals with ID about death and bereavement.

PMID- 29044767
TI  - "Why Anatomy is neglected or mistaught".

PMID- 29044765
TI  - A novel inborn error of the coenzyme Q10 biosynthesis pathway: cerebellar ataxia
      and static encephalomyopathy due to COQ5 C-methyltransferase deficiency.
AB  - Primary coenzyme Q10 (CoQ10 ; MIM# 607426) deficiencies are an emerging group of
      inherited mitochondrial disorders with heterogonous clinical phenotypes. Over a
      dozen genes are involved in the biosynthesis of CoQ10 , and mutations in several
      of these are associated with human disease. However, mutations in COQ5 (MIM#
      616359), catalyzing the only C-methylation in the CoQ10 synthetic pathway, have
      not been implicated in human disease. Here, we report three female siblings of
      Iraqi-Jewish descent, who had varying degrees of cerebellar ataxia,
      encephalopathy, generalized tonic-clonic seizures, and cognitive disability.
      Whole-exome and subsequent whole-genome sequencing identified biallelic
      duplications in the COQ5 gene, leading to reduced levels of CoQ10 in peripheral
      white blood cells of all affected individuals and reduced CoQ10 levels in the
      only muscle tissue available from one affected proband. CoQ10 supplementation led
      to clinical improvement and increased the concentrations of CoQ10 in blood. This
      is the first report of primary CoQ10 deficiency caused by loss of function of
      COQ5, with delineation of the clinical, laboratory, histological, and molecular
      features, and insights regarding targeted treatment with CoQ10 supplementation.

PMID- 29044769
TI  - Human papillomavirus vaccination of adult women and risk of autoimmune and
      neurological diseases.
AB  - BACKGROUND: Since 2006, human papillomavirus (HPV) vaccines have been introduced
      in many countries worldwide. Whilst safety studies have been reassuring, focus
      has been on the primary target group, the young adolescent girls. However, it is
      also important to evaluate safety in adult women where background disease rates
      and safety issues could differ significantly. OBJECTIVE: We took advantage of the
      unique Danish and Swedish nationwide healthcare registers to conduct a cohort
      study comparing incidence rate ratios (RRs) of 45 preselected serious chronic
      diseases in quadrivalent HPV (qHPV)-vaccinated and qHPV-unvaccinated adult women
      18-44 years of age. METHODS: We used Poisson regression to estimate RRs according
      to qHPV vaccination status with two-sided 95% confidence intervals (95% CIs).
      RESULTS: The study cohort comprised 3 126 790 women (1 195 865 [38%] Danish and 1
      930 925 [62%] Swedish) followed for 16 386 459 person-years. Vaccine uptake of at
      least one dose of qHPV vaccine was 8% in the cohort: 18% amongst Danish women and
      2% amongst Swedish. We identified seven adverse events with statistically
      significant increased risks following vaccination-Hashimoto's thyroiditis,
      coeliac disease, localized lupus erythematosus, pemphigus vulgaris, Addison's
      disease, Raynaud's disease and other encephalitis, myelitis or encephalomyelitis.
      After taking multiple testing into account and conducting self-controlled case
      series analyses, coeliac disease (RR 1.56 [95% confidence interval 1.29-1.89])
      was the only remaining association. CONCLUSION: Unmasking of conditions at
      vaccination visits is a plausible explanation for the increased risk associated
      with qHPV in this study because coeliac disease is underdiagnosed in Scandinavian
      populations. In conclusion, our study of serious adverse event rates in qHPV
      vaccinated and qHPV-unvaccinated adult women 18-44 years of age did not raise any
      safety issues of concern.

PMID- 29044768
TI  - Prevalence of Osteoporosis and Low Bone Mass Among Puerto Rican Older Adults.
AB  - Historically, osteoporosis has not been considered a public health priority for
      the Hispanic population. However, recent data indicate that Mexican Americans are
      at increased risk for this chronic condition. Although it is well established
      that there is heterogeneity in social, lifestyle, and health-related factors
      among Hispanic subgroups, there are currently few studies on bone health among
      Hispanic subgroups other than Mexican Americans. The current study aimed to
      determine the prevalence of osteoporosis and low bone mass (LBM) among 953 Puerto
      Rican adults, aged 47 to 79 years and living on the US mainland, using data from
      one of the largest cohorts on bone health in this population: The Boston Puerto
      Rican Osteoporosis Study (BPROS). Participants completed an interview to assess
      demographic and lifestyle characteristics and bone mineral density measures. To
      facilitate comparisons with national data, we calculated age-adjusted estimates
      for osteoporosis and LBM for Mexican American, non-Hispanic white, and non
      Hispanic black adults, aged >=50 years, from the National Health and Nutrition
      Examination Survey (NHANES). The overall prevalence of osteoporosis and LBM were
      10.5% and 43.3% for participants in the BPROS, respectively. For men, the highest
      prevalence of osteoporosis was among those aged 50 to 59 years (11%) and lowest
      for men >=70 years (3.7%). The age-adjusted prevalence of osteoporosis for Puerto
      Rican men was 8.6%, compared with 2.3% for non-Hispanic white, and 3.9% for
      Mexican American men. There were no statistically significant differences between
      age-adjusted estimates for Puerto Rican women (10.7%), non-Hispanic white women
      (10.1%), or Mexican American women (16%). There is a need to understand specific
      factors contributing to osteoporosis in Puerto Rican adults, particularly younger
      men. This will provide important information to guide the development of
      culturally and linguistically tailored interventions to improve bone health in
      this understudied and high-risk population. (c) 2017 American Society for Bone
      and Mineral Research.

PMID- 29044770
TI  - Effects of forced, passive, and voluntary exercise on spinal motoneurons changes
      after peripheral nerve injury.
AB  - After peripheral nerve injury, there are important changes at the spinal level
      that can lead to disorganization of the central circuitry and thus compromise
      functional recovery even if axons are able to successfully regenerate and
      reinnervate their target organs. Physical rehabilitation is a promising strategy
      to modulate these plastic changes and thus to improve functional recovery after
      the damage of the nervous system. Forced exercise in a treadmill is able to
      partially reverse the synaptic stripping and the loss of perineuronal nets that
      motoneurons suffer after peripheral nerve injury in animal models. The aim of
      this study was to investigate whether passive exercise, by means of cycling in a
      motorized bicycle, or voluntary free running in a wheel is able to mimic the
      effects induced by forced exercise on the changes that axotomized motoneurons
      suffer after peripheral nerve injury. Partial preservation of synapses and
      perineuronal nets was observed only in axotomized motoneurons from animals
      subjected to high-intensity cycling and the ones that freely ran long distances,
      but not when low-intensity exercise protocols were applied. Therefore, the
      intensity but not the type of exercise used is the key element to prevent
      synaptic stripping and loss of perineuronal nets in motoneurons after axotomy.

PMID- 29044771
TI  - Alkaloids of Amaryllidaceae as Inhibitors of Cholinesterases (AChEs and BChEs):
      An Integrated Bioguided Study.
AB  - INTRODUCTION: Enzymatic inhibition of acetylcholinesterase (AChE) is an essential
      therapeutic target for the treatment of Alzheimer's disease (AD) and AChE
      inhibitors are the first-line drugs for it treatment. However,
      butyrylcholinesterase (BChE), contributes critically to cholinergic dysfunction
      associated with AD. Thus, the development of novel therapeutics may involve the
      inhibition of both cholinesterase enzymes. OBJECTIVE: To evaluate, in an
      integrated bioguided study, cholinesterases alkaloidal inhibitors of
      Amaryllidaceae species. METHODOLOGY: The proposed method combines high
      performance thin-layer chromatography (HPTLC) with data analysis by densitometry,
      enzymatic bioautography with different AChEs and BChEs, the detection of
      bioactive molecules through gas chromatography mass spectrometry (GC-MS) analysis
      of spots of interest, and theoretical in silico studies. RESULTS: To evaluate the
      bioguided method, the AChE and BChE inhibitory activities of seven Amaryllidaceae
      plant extracts were evaluated. The alkaloid extracts of Eucharis bonplandii
      exhibited a high level of inhibitory activity (IC50  = 0.72 +/- 0.05 MUg/mL)
      against human recombinant AChE (hAChE). Regarding human serum BChE (hBChE), the
      bulb and leaf extracts of Crinum jagus had the highest activity (IC50  = 8.51 +/-
      0.56 MUg/mL and 11.04 +/- 1.21 MUg/mL, respectively). In the HPTLC spots with
      high inhibitory activity, several alkaloids were detected using GC-MS, and some
      of these alkaloids were identified. Galanthamine, galanthamine N-oxide and
      powelline should be the most prominent inhibitors of substrate accommodation in
      the active site of the Torpedo californica AChE (TcAChE), hAChE and hBChE
      enzymes. CONCLUSIONS: These results are evidence of the chemical relevance of the
      Colombian's Amaryllidaceae species for the inhibition of cholinesterases and as
      potent sources for the palliative treatment of AD. Copyright (c) 2017 John Wiley
      & Sons, Ltd.

PMID- 29044772
TI  - RD Lawrence Lecture 2017 Incretins: the intelligent hormones in diabetes.
AB  - The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and
      glucagon-like peptide-1 (GLP-1) have attracted considerable scientific and
      clinical interest due largely to their insulin-releasing and glucose-lowering
      properties. Indeed, GLP-1-based therapies are now key treatment options for many
      people with diabetes worldwide. In contrast, GIP-based agents have yet to reach
      the clinic based primarily on the impaired insulinotropic action of GIP observed
      in people with diabetes. Nevertheless, GIP is a key physiological regulator of
      insulin secretion and stable forms of GIP show much promise in rodent models to
      alleviate diabetes-obesity. Recent studies suggest that GIP may have an important
      role to play in a combination therapeutic approach or bioengineered with other
      gut peptides. Moreover, recent experimental studies indicate that incretins also
      exert pleiotropic effects in regions of the brain associated with learning and
      memory, thereby supporting preclinical data demonstrating that incretin-based
      drugs improve cognitive function. This review article, based on the RD Lawrence
      Lecture presented at Diabetes UK Annual Professional Conference (2017), provides
      a brief overview of incretins with a major focus on GIP, the development of
      designer GIP analogues, and how these molecules can improve cognition. Thus,
      incretins can be considered as 'the intelligent hormones' and may hold the key to
      successfully treating the alarming rise in neurodegenerative disorders.

PMID- 29044773
TI  - Integrated analysis of microRNA and mRNA expression profiles in the rat spinal
      cord under inflammatory pain conditions.
AB  - Recent studies using microarray-based approaches have demonstrated that microRNAs
      (miRNAs) are involved in pain processing pathways. However, a significant
      proportion of computational predictions of miRNA targets are false-positive
      interactions. To increase the chance of identifying biologically relevant
      targets, we performed an integrated analysis of both miRNA and mRNA expression
      profiles in the rat spinal cord during complete Freund's adjuvant (CFA)-induced
      inflammatory pain. We generated miRNA and mRNA arrays from the same corresponding
      samples on days 5 and 14 after CFA injection. Five miRNAs and 1096 mRNAs in the
      CFA 5d group and 16 miRNAs and 647 mRNAs in the CFA 14d group were differentially
      expressed based on a filter of at least a 1.5-fold change in either direction. An
      integrated analysis revealed 54 mRNA targets with an inverse correlation to the
      expression patterns of three miRNAs in the CFA 5d group. Seventy-five targets
      were inversely correlated to six miRNAs in the CFA 14d group. The miRNA-mRNA
      interaction networks revealed significant changes in miR-124, miR-149, miR-3584
      and their target genes, IL-6R, ADAM19, LAMC1 and CERS2, in the CFA 5d group. In
      the CFA 14d group, significant changes were noted in miR-124, miR-29, miR-34, miR
      30, miR-338 and their target genes, TIMP2, CREB5 and EFNB1. We also investigated
      an interaction pair, miR-124-3p and IL-6R, and the results showed that miR-124-3p
      could attenuate inflammatory pain and decrease IL-6R expression in the spinal
      cord. These specific miRNAs and their target genes provide possible avenues for
      the diagnosis and treatment of inflammatory pain.

PMID- 29044774
TI  - Three-dimensional distribution of tyrosine hydroxylase, vasopressin and oxytocin
      neurones in the transparent postnatal mouse brain.
AB  - Over the years, advances in immunohistochemistry techniques have been a critical
      step in detecting and mapping neuromodulatory substances in the central nervous
      system. The better quality and specificity of primary antibodies, new staining
      procedures and the spectacular development of imaging technologies have allowed
      such progress. Very recently, new methods permitting tissue transparency have
      been successfully used on brain tissues. In the present study, we combined whole
      mount immunostaining for tyrosine hydroxylase (TH), oxytocin (OXT) and arginine
      vasopressin (AVP), with the iDISCO+ clearing method, light-sheet microscopy and
      semi-automated counting of three-dimensionally-labelled neurones to obtain a (3D)
      distribution of these neuronal populations in a 5-day postnatal (P5) mouse brain.
      Segmentation procedure and 3D reconstruction allowed us, with high resolution, to
      map TH staining of the various catecholaminergic cell groups and their ascending
      and descending fibre pathways. We show that TH pathways are present in the whole
      P5 mouse brain, similar to that observed in the adult rat brain. We also provide
      new information on the postnatal distribution of OXT and AVP immunoreactive cells
      in the mouse hypothalamus, and show that, compared to AVP neurones, OXT neurones
      in the supraoptic (SON) and paraventricular (PVN) nuclei are not yet mature in
      the early postnatal period. 3D semi-automatic quantitative analysis of the PVN
      reveals that OXT cell bodies are more numerous than AVP neurones, although their
      immunoreactive soma have a volume half smaller. More AVP nerve fibres compared to
      OXT were observed in the PVN and the retrochiasmatic area. In conclusion, the
      results of the present study demonstrate the utility and the potency of imaging
      large brain tissues with clearing procedures coupled to novel 3D imaging
      technologies to study, localise and quantify neurotransmitter substances involved
      in brain and neuroendocrine functions.

PMID- 29044775
TI  - Flexible, High-Wettability and Fire-Resistant Separators Based on Hydroxyapatite
      Nanowires for Advanced Lithium-Ion Batteries.
AB  - Separators play a pivotal role in the electrochemical performance and safety of
      lithium-ion batteries (LIBs). The commercial microporous polyolefin-based
      separators often suffer from inferior electrolyte wettability, low thermal
      stability, and severe safety concerns. Herein, a novel kind of highly flexible
      and porous separator based on hydroxyapatite nanowires (HAP NWs) with excellent
      thermal stability, fire resistance, and superior electrolyte wettability is
      reported. A hierarchical cross-linked network structure forms between HAP NWs and
      cellulose fibers (CFs) via hybridization, which endows the separator with high
      flexibility and robust mechanical strength. The high thermal stability of HAP NW
      networks enables the separator to preserve its structural integrity at
      temperatures as high as 700  degrees C, and the fire-resistant property of HAP
      NWs ensures high safety of the battery. In particular, benefiting from its unique
      composition and highly porous structure, the as-prepared HAP/CF separator
      exhibits near zero contact angle with the liquid electrolyte and high electrolyte
      uptake of 253%, indicating superior electrolyte wettability compared with the
      commercial polyolefin separator. The as-prepared HAP/CF separator has unique
      advantages of superior electrolyte wettability, mechanical robustness, high
      thermal stability, and fire resistance, thus, is promising as a new kind of
      separator for advanced LIBs with enhanced performance and high safety.

PMID- 29044776
TI  - Bioinspired Heterogeneous Structural Color Stripes from Capillaries.
AB  - As an important characteristic of many creatures, structural colors play a
      crucial role in the survival of organisms. Inspired by these features, an
      intelligent structural color material with a heterogeneous striped pattern and
      stimuli-responsivity by fast self-assembly of colloidal nanoparticles in
      capillaries with a certain diameter range are presented here. The width, spacing,
      color, and even combination of the structural color stripe patterns can be
      precisely tailored by adjusting the self-assembly parameters. Attractively, with
      the integration of a near-infrared (NIR) light responsive graphene hydrogel into
      the structural color stripe pattern, the materials are endowed with light
      controlled reversible bending behavior with self-reporting color indication. It
      is demonstrated that the striped structural color materials can be used as NIR
      light-triggered dynamic barcode labels for the anti-counterfeiting of different
      products. These features of the bioinspired structural color stripe pattern
      materials indicate their potential values for mimicking structural color
      organisms, which will find important applications in constructing intelligent
      sensors, anti-counterfeiting devices, and so on.

PMID- 29044777
TI  - Rhodium-Induced Reversible C-C Bond Cleavage: Transformations of Rhodium(III) 22
      Alkyl-m-benziporphyrins.
AB  - The structurally prearranged carbaporphyrins 22-methyl- and 22-ethyl-m
      benziporphyrins provide the platform stabilizing aromatic rhodium(III) 22-(MU
      methylene-m-benziporphyrin) and rhodium(III) 22-(MU-ethylidene-m-benziporphyrin).
      An intramolecular conversion facilitated by the m-phenylene reactivity and
      observed for both aromatic complexes efficiently leads to rhodium(III) 21-(MU
      methylene)-21-carbaporphyrin and rhodium(III) 21-(MU-ethylidene)-21
      carbaporphyrin. The distinctive macrocyclic environment of rhodium(III) 21
      carbaporphyrin created an opportunity to trap unique organometallic
      transformations of inner core substituents affording the fulvene-like bond
      pattern or the rearrangement to 21-vinyl substituent. The one-electron reduction
      of the rhodium(III) carbaporphyrin anion pi-radical with a (dxy )2 (dxz )2 (dyz
      )2 -(P.- ) electronic configuration is demonstrated. The further process of
      reduction of paramagnetic species triggers the ethyl migration from carbon(22) to
      rhodium(III), affording the diamagnetic rhodium(III) meta-benziporphyrin
      containing the apically coordinated sigma-ethyl ligand providing an example of
      reversible C(sp2 )-C(sp3 ) bond cleavage.

PMID- 29044778
TI  - The impact diverging public opinion on cannabis and tobacco regulation has on
      constructive engagement between advocates.

PMID- 29044779
TI  - Exocrine pancreas function decreases during the progression of the beta-cell
      damaging process in young prediabetic children.
AB  - OBJECTIVE: The function of the exocrine pancreas is decreased in patients with
      type 1 diabetes but it is not known when this defect develops. The current study
      set out to determine whether the reduced exocrine function becomes manifest after
      the initiation of islet autoimmunity. METHODS: The study was nested in the
      prospective Type 1 Diabetes Prediction and Prevention study where children with
      human leukocyte antigen (HLA)-conferred susceptibility are observed from birth.
      Elastase-1 levels were analyzed from stool samples collected at the time of
      seroconversion to islet autoantibody positivity and at diagnosis of type 1
      diabetes, as well as from samples taken from matched control children of similar
      age. RESULTS: Elastase levels were lower in case children at the time of the
      diagnosis of diabetes when compared to the control children. However, elastase
      concentrations did not differ between cases and controls at the time when
      autoantibodies appeared. CONCLUSION: The results suggest that the defect in the
      exocrine function develops after the appearance of islet autoantibodies. Further
      studies are needed to assess whether reduced elastase levels predict rapid
      progression of islet autoimmunity to clinical disease.

PMID- 29044781
TI  - The language of diabetes: the good, the bad and the ugly.

PMID- 29044780
TI  - 'Hot' vs. 'cold' behavioural-cognitive styles: motivational-dopaminergic vs.
      cognitive-cholinergic processing of a Pavlovian cocaine cue in sign- and goal
      tracking rats.
AB  - Discrete Pavlovian reward cues acquire more potent incentive motivational
      properties (incentive salience) in some animals (sign-trackers; STs) compared to
      others (goal-trackers; GTs). Conversely, GTs appear to be better than STs in
      processing more complex contextual cues, perhaps reflecting their relatively
      greater bias for goal-directed cue processing. Here, we investigated the activity
      of two major prefrontal neuromodulatory input systems, dopamine (DA) and
      acetylcholine (ACh), in response to a discrete Pavlovian cue that was previously
      paired with cocaine administration in STs and GTs. Rats underwent Pavlovian
      training in which light cue presentations were either paired or unpaired with an
      intravenous cocaine infusion. Following a 10-day abstinence period, prefrontal
      dialysates were collected in STs and GTs during cue presentations in the absence
      of cocaine. In STs, the cue previously paired with cocaine significantly
      increased prefrontal DA levels. DA levels remained elevated over baseline across
      multiple cue presentation blocks, and DA levels and approaches to the cue were
      significantly correlated. In STs, ACh levels were unaffected by cue
      presentations. In contrast, in GTs, presentations of the cocaine cue increased
      prefrontal ACh, but not DA, levels. GTs oriented towards the cue at rates similar
      to STs, but they did not approach it and elevated ACh levels did not correlate
      with conditioned orientation. The results indicate a double dissociation between
      the role of prefrontal DA and ACh in STs and GTs, and suggest that these
      phenotypes will be useful for studying the role of neuromodulator systems in
      mediating opponent behavioural-cognitive styles.

PMID- 29044782
TI  - Phylogenomics of pike cichlids (Cichlidae: Crenicichla): the rapid ecological
      speciation of an incipient species flock.
AB  - The rapid rise of phenotypic and ecological diversity in independent lake
      dwelling groups of cichlids is emblematic of the East African Great Lakes. In
      this study, we show that similar ecologically based diversification has occurred
      in pike cichlids (Crenicichla) throughout the Uruguay River drainage of South
      America. We collected genomic data from nearly 500 ultraconserved element (UCEs)
      loci and >260 000 base pairs across 33 species, to obtain a phylogenetic
      hypothesis for the major species groups and to evaluate the relationships and
      genetic structure among five closely related, endemic, co-occurring species (the
      Uruguay River species flock; URSF). Additionally, we evaluated ecological
      divergence of the URSF based on body and lower pharyngeal jaw (LPJ) shape and gut
      contents. Across the genus, we recovered novel relationships among the species
      groups. We found strong support for the monophyly of the URSF; however,
      relationships among these species remain problematic, likely because of the rapid
      and recent evolution of this clade. Clustered co-ancestry analysis recovered most
      species as well delimited genetic groups. The URSF species exhibit species
      specific body and LPJ shapes associated with specialized trophic roles.
      Collectively, our results suggest that the URSF consists of incipient species
      that arose via ecological speciation associated with the exploration of novel
      trophic roles.

PMID- 29044783
TI  - Cryptomarkets, systemic violence and the 'gentrification hypothesis'.

PMID- 29044784
TI  - Mechanism-Based Inhibitors of the Human Sirtuin 5 Deacylase: Structure-Activity
      Relationship, Biostructural, and Kinetic Insight.
AB  - The sirtuin enzymes are important regulatory deacylases in a variety of
      biochemical contexts and may therefore be potential therapeutic targets through
      either activation or inhibition by small molecules. Here, we describe the
      discovery of the most potent inhibitor of sirtuin 5 (SIRT5) reported to date. We
      provide rationalization of the mode of binding by solving co-crystal structures
      of selected inhibitors in complex with both human and zebrafish SIRT5, which
      provide insight for future optimization of inhibitors with more "drug-like"
      properties. Importantly, enzyme kinetic evaluation revealed a slow, tight-binding
      mechanism of inhibition, which is unprecedented for SIRT5. This is important
      information when applying inhibitors to probe mechanisms in biology.

PMID- 29044785
TI  - Hysteretic Two-Step Spin-Crossover Behavior in Two Two-Dimensional Hofmann-Type
      Coordination Polymers.
AB  - The reaction of ferrous salts and square-planar tetracyanometallates [MII (CN)4
      ]2- (M=Pd, Pt) with ligand 4-(1H-pyrazol-3-yl)pyridine (Hppy) resulted in the
      formation of two two-dimensional (2D) Hofmann-like coordination polymers (CPs)
      with the general formula of {FeII (Hppy)2 [MII (CN)4 ]}?H2 O (M=Pd for 1Pd , Pt
      for 1Pt ). The two CPs have been studied by variable-temperature single-crystal X
      ray crystallography, differential scanning calorimetry, and magnetic
      measurements. Polymers 1Pd and 1Pt are isostructures, in which the FeII atoms are
      equatorially coordinated with [MII (CN)4 ]2- to form 2D undulating layers and
      axially coordinated with Hppy ligands. Both compounds undergo cooperative,
      complete spin crossover (SCO), with characteristic abrupt and remarkable two
      equal steps, featuring hysteresis widths of 14 K and 19 K (1Pd ) and 17 and 23 K
      (1Pt ) for the two steps. The SCO cooperativity may result from the hydrogen
      bonds and pi???pi interactions within and between such 2D layers, and the two
      step SCO behavior is accompanied with phase transitions.

PMID- 29044787
TI  - Intracardiac ablation for atrioventricular nodal reentry tachycardia using a 6 mm
      distal electrode cryoablation catheter: Prospective, multicenter, North American
      study (ICY-AVNRT STUDY).
AB  - INTRODUCTION: Radiofrequency (RF) ablation is effective for slow pathway
      ablation, but carries a risk of inadvertent AV block requiring permanent pacing.
      By comparison, cryoablation with a 4-mm distal electrode catheter has not been
      reported to cause permanent AV block but has been shown to be less effective than
      RF ablation. We sought to define the safety and efficacy of a 6-mm distal
      electrode cryoablation catheter for slow pathway ablation in patients with
      atrioventricular nodal reentry tachycardia (AVNRT). METHODS AND RESULTS: Twenty
      six U.S. and eight Canadian centers participated in the study. Patients with
      supraventricular tachycardia (SVT) thought likely to be AVNRT were enrolled. If
      AVNRT was inducible and confirmed to be the clinical SVT, then the slow pathway
      was targeted with a cryoablation catheter using a standardized protocol of best
      practices. Acute success was defined as inducibility of no more than one echo
      beat after cryoablation. Primary efficacy was defined as acute success and the
      absence of documented recurrent AVNRT over 6 months of follow-up. Primary safety
      was a composite of serious procedure-related adverse events and/or device-related
      complications. Note that 397 subjects met enrollment criteria after the EP study
      and received cryoablation. Mean ablation procedure duration (including a waiting
      period) was 89 +/- 40 minutes, and mean fluoroscopy time was 4.8 +/- 5.9 minutes.
      Isoproterenol was administered before cryoablation in 53% and after the last
      lesion in 85% of cases. Acute procedural success was realized in 95% (378 of 397)
      of subjects. No subject received a permanent pacemaker due to AV block. The slow
      pathway could not be ablated in 19 subjects, including: 12 due to inefficacy, 2
      due to transient AV block, and 5 due to both inefficacy and transient AV block.
      RF ablation was used in the same procedure in 11 of 19 failed subjects, and was
      ineffective in 3 subjects. Among the group with acute success, 10 subjects (2.7%)
      had documented recurrent AVNRT over the 6-month follow-up period, and all
      occurred within 3 months of the index cryoablation. Serious procedure-related
      adverse events occurred in 4 subjects (1.0%), including one each: tamponade,
      pulmonary embolism, femoral vein hemorrhage, and diagnostic EP catheter knotting.
      None of these serious adverse events were related to use of the cryoablation
      catheter. Overall, 93% of subjects had successful slow pathway ablation at 6
      months with the study cryoablation catheter. CONCLUSIONS: Cryoablation for AVNRT
      using a focal 6-mm catheter was safe and effective. It resulted in a low risk of
      recurrence over 6 months of follow-up with no incidence of AV block requiring
      permanent pacing.

PMID- 29044786
TI  - Unique profile of antimicrobial peptide expression in polymorphic light eruption
      lesions compared to healthy skin, atopic dermatitis, and psoriasis.
AB  - BACKGROUND: Polymorphic light eruption (PLE) has been attributed to type IV, most
      likely delayed-type hypersensitivity response (adaptive immunity) but little is
      known on innate immunity, especially antimicrobial peptides (AMPs) in the
      disease. Abnormalities in AMP expression have been linked to pathological skin
      conditions such as atopic dermatitis (AD) and psoriasis. METHODS: Antimicrobial
      peptide profiling was carried out in PLE skin samples (n,12) compared with that
      of healthy (n,13), atopic (n,6), and psoriatic skin (n,6). RESULTS: Compared to
      healthy skin, we observed increased expression of psoriasin and RNAse7 (both
      mostly in stratum granulosum of the epidermis), HBD-2 (in the cellular infiltrate
      of the dermis), and LL37 (mostly in and around blood vessels and glands) in PLE
      lesional skin, a similar expression profile as present in psoriatic skin and
      different to that of AD (with little or no expression of psoriasin, RNAse7, HBD
      2, and LL37). HBD-3 was downregulated in PLE compared to its high expression in
      the epidermis and dermis of healthy skin, AD, and psoriasis. CONCLUSION: The
      unique profile of differentially expressed AMPs in PLE implies a role in the
      pathophysiology of the disease, possibly directly or indirectly linked to the
      microbiome of the skin.

PMID- 29044788
TI  - Management of the lateral neck compartment in patients with sporadic medullary
      thyroid cancer.
AB  - BACKGROUND: The purpose of this retrospective analysis was to evaluate the
      benefits of an elective lateral neck dissection (ELND) in patients with medullary
      thyroid cancer (MTC) without radiographically apparent lateral neck metastases.
      METHODS: Patients with sporadic MTC without radiographic evidence of lateral neck
      metastasis who underwent definitive surgery were divided into 2 groups based on
      surgical approach: no ELND (the observation group) and ipsilateral or bilateral
      ELND (the ELND group). Primary outcomes were biochemical cure, locoregional
      recurrence, distant metastasis, and overall survival (OS). RESULTS: Sixty-six
      patients met inclusion criteria: 44 patients (67%) in the observation group and
      22 patients (33%) in the ELND group. Two of 44 patients (5%) in the observation
      group developed subsequent (ipsilateral) lateral neck disease. At last follow-up,
      locoregional disease control rates among the observation and ELND groups were 98%
      and 100% (P > .999), respectively, whereas biochemical cure rates were 82% and
      85% (P > .999), respectively, and 5-year OSs were 84% and 100% (P = .156),
      respectively. CONCLUSION: Patients with MTC without lateral neck metastasis have
      similar biochemical cure rates with observation or elective dissection of lateral
      neck compartments.

PMID- 29044790
TI  - Acute appendicitis.
AB  - Acute appendicitis is the most common reason for abdominal surgery in children.
      Luminal obstruction of the appendix progresses to suppurative inflammation and
      perforation, which causes generalised peritonitis or an appendix mass/abscess.
      Classical features include periumbilical pain that migrates to the right iliac
      fossa, anorexia, fever, and tenderness and guarding in the right iliac fossa.
      Atypical presentations are particularly common in preschool children. A clinical
      diagnosis is possible in most cases, after a period of active observation if
      necessary; inflammatory markers and an ultrasound scan are useful investigations
      when the diagnosis is uncertain. Treatment is by appendicectomy after appropriate
      fluid resuscitation, analgesia and intravenous antibiotics. Laparoscopic
      appendicectomy is better than open appendicectomy in most cases because it is
      associated with less postoperative pain and a shorter hospital stay, but recovery
      after acute appendicitis is mostly dictated by whether the appendix was
      perforated or not. Management of the appendix mass remains controversial and not
      all affected children need an interval appendicectomy. This article discusses
      tips and pitfalls in diagnosis and addresses many of the controversies that
      surround the management of this condition.

PMID- 29044791
TI  - The role of driving factors in historical and projected carbon dynamics of upland
      ecosystems in Alaska.
AB  - It is important to understand how upland ecosystems of Alaska, which are
      estimated to occupy 84% of the state (i.e., 1,237,774 km2 ), are influencing and
      will influence state-wide carbon (C) dynamics in the face of ongoing climate
      change. We coupled fire disturbance and biogeochemical models to assess the
      relative effects of changing atmospheric carbon dioxide (CO2 ), climate, logging
      and fire regimes on the historical and future C balance of upland ecosystems for
      the four main Landscape Conservation Cooperatives (LCCs) of Alaska. At the end of
      the historical period (1950-2009) of our analysis, we estimate that upland
      ecosystems of Alaska store ~50 Pg C (with ~90% of the C in soils), and gained
      3.26 Tg C/yr. Three of the LCCs had gains in total ecosystem C storage, while the
      Northwest Boreal LCC lost C (-6.01 Tg C/yr) because of increases in fire
      activity. Carbon exports from logging affected only the North Pacific LCC and
      represented less than 1% of the state's net primary production (NPP). The
      analysis for the future time period (2010-2099) consisted of six simulations
      driven by climate outputs from two climate models for three emission scenarios.
      Across the climate scenarios, total ecosystem C storage increased between 19.5
      and 66.3 Tg C/yr, which represents 3.4% to 11.7% increase in Alaska upland's
      storage. We conducted additional simulations to attribute these responses to
      environmental changes. This analysis showed that atmospheric CO2 fertilization
      was the main driver of ecosystem C balance. By comparing future simulations with
      constant and with increasing atmospheric CO2 , we estimated that the sensitivity
      of NPP was 4.8% per 100 ppmv, but NPP becomes less sensitive to CO2 increase
      throughout the 21st century. Overall, our analyses suggest that the decreasing
      CO2 sensitivity of NPP and the increasing sensitivity of heterotrophic
      respiration to air temperature, in addition to the increase in C loss from
      wildfires weakens the C sink from upland ecosystems of Alaska and will ultimately
      lead to a source of CO2 to the atmosphere beyond 2100. Therefore, we conclude
      that the increasing regional C sink we estimate for the 21st century will most
      likely be transitional.

PMID- 29044792
TI  - Metal-Catalyzed Group-Transfer Polymerization: A Versatile Tool for Tailor-Made
      Functional (Co)Polymers.
AB  - Accommodating the increasing demand for tailor-made polymers is a major goal in
      polymer chemistry. Therefore, the investigation of polymerization techniques,
      which allow the precise synthesis of macromolecules is of exceptional interest.
      Ionic or controlled radical polymerization are capable living-type methods for
      the generation of uniform polymers. However, even these approaches reach their
      limits in certain issues. In the last decades, group-transfer polymerization
      (GTP) and especially metal-catalyzed GTP have proven to give access to a plethora
      of tailor-made homo- and copolymers based on alpha,beta-unsaturated monomers.
      Thereby, GTP has established its potential in the development of functional and
      smart polymers. This concept article highlights the most significant progress in
      metal-catalyzed GTP with a focus on functional (co)polymers including different
      polymeric architectures and microstructures.

PMID- 29044793
TI  - Clustering of prevention behaviours in patients with high-risk primary melanoma.
AB  - OBJECTIVE: Because melanoma patients are at high risk of further disease, we
      aimed to study their melanoma prevention behaviours. METHODS: In a large cohort
      of patients newly diagnosed with high-risk melanoma in Queensland, Australia, we
      assessed clustering of preventive behaviours using latent class analysis. We
      assessed associated factors with prevalence proportion ratios (PPRs) and 95%
      confidence intervals (CIs) estimated by Poisson regression and also if preventive
      behaviour was associated with better tumour prognosis at diagnosis. RESULTS:
      Among 789 primary melanoma patients (57% male; 21% with previous melanoma), we
      identified 4 different behaviour clusters: "no/ low prevention" (34% of cohort),
      "sun protection only" (25%), "skin checks only" (25%), and "sun protection and
      skin checks" (17%). Prevalence of clusters differed between males and females and
      also the component behaviours. Preventive behaviours were associated with having
      skin that burned and past cutaneous cancer, and for males, combined sun
      protective and skin checking behaviour was associated with higher education and
      non-smoking. In patients with no past history of cutaneous cancer, males in the
      "skin checks only" cluster had significantly reduced chances of a thick (poor
      prognosis) melanoma (PPR = 0.79, 95% CI 0.68, 0.91) and females in the "sun
      protection and skin checks" cluster were significantly less likely to have an
      ulcerated melanoma (PPR = 0.85, 95% CI 0.74, 0.98) compared with the "no/ low
      prevention" cluster. CONCLUSION: These findings allow tailoring of preventive
      advice to melanoma patients to reduce their risk of future primary and recurrent
      disease.

PMID- 29044794
TI  - Engineering 2D Nanofluidic Li-Ion Transport Channels for Superior Electrochemical
      Energy Storage.
AB  - Rational surface engineering of 2D nanoarchitectures-based electrode materials is
      crucial as it may enable fast ion transport, abundant-surface-controlled energy
      storage, long-term structural integrity, and high-rate cycling performance. Here
      we developed the stacked ultrathin Co3 O4 nanosheets with surface
      functionalization (SUCNs-SF) converted from layered hydroxides with inheritance
      of included anion groups (OH- , NO3- , CO32- ). Such stacked structure
      establishes 2D nanofluidic channels offering extra lithium storage sites,
      accelerated Li-ion transport, and sufficient buffering space for volume change
      during electrochemical processes. Tested as an anode material, this unique
      nanoarchitecture delivers high specific capacity (1230 and 1011 mAh g-1 at 0.2
      and 1 A g-1 , respectively), excellent rate performance, and long cycle
      capability (1500 cycles at 5 A g-1 ). The demonstrated advantageous features by
      constructing 2D nanochannels in nonlayered materials may open up possibilities
      for designing high-power lithium ion batteries.

PMID- 29044795
TI  - AHNS Series: Do you know your guidelines? Perioperative antithrombotic management
      in head and neck surgery.
AB  - Head and neck surgeons are commonly faced with surgical patients who have
      underlying medical problems requiring antithrombotic therapy. It is difficult to
      achieve a balance between minimizing the risk of thromboembolism and hemorrhage
      in the perioperative period. Data from randomized, controlled trials are limited,
      and procedure-specific bleed rates are also difficult to pinpoint. The decision
      is made more difficult when patients with moderate-to-high risk for
      thromboembolic events undergo procedures that are high risk for bleeding. This is
      true for many head and neck oncologic surgeries. Furthermore, although elective
      procedures may be delayed for optimization of antithrombotic medication, emergent
      procedures cannot. Head and neck surgery often represents the most challenging of
      all these circumstances, given the potential risk of airway compromise from
      bleeding after head and neck surgery.

PMID- 29044796
TI  - Social traits, social networks and evolutionary biology.
AB  - The social environment is both an important agent of selection for most
      organisms, and an emergent property of their interactions. As an aggregation of
      interactions among members of a population, the social environment is a product
      of many sets of relationships and so can be represented as a network or matrix.
      Social network analysis in animals has focused on why these networks possess the
      structure they do, and whether individuals' network traits, representing some
      aspect of their social phenotype, relate to their fitness. Meanwhile,
      quantitative geneticists have demonstrated that traits expressed in a social
      context can depend on the phenotypes and genotypes of interacting partners,
      leading to influences of the social environment on the traits and fitness of
      individuals and the evolutionary trajectories of populations. Therefore, both
      fields are investigating similar topics, yet have arrived at these points
      relatively independently. We review how these approaches are diverged, and yet
      how they retain clear parallelism and so strong potential for complementarity.
      This demonstrates that, despite separate bodies of theory, advances in one might
      inform the other. Techniques in network analysis for quantifying social
      phenotypes, and for identifying community structure, should be useful for those
      studying the relationship between individual behaviour and group-level
      phenotypes. Entering social association matrices into quantitative genetic models
      may also reduce bias in heritability estimates, and allow the estimation of the
      influence of social connectedness on trait expression. Current methods for
      measuring natural selection in a social context explicitly account for the fact
      that a trait is not necessarily the property of a single individual, something
      the network approaches have not yet considered when relating network metrics to
      individual fitness. Harnessing evolutionary models that consider traits affected
      by genes in other individuals (i.e. indirect genetic effects) provides the
      potential to understand how entire networks of social interactions in populations
      influence phenotypes and predict how these traits may evolve. By theoretical
      integration of social network analysis and quantitative genetics, we hope to
      identify areas of compatibility and incompatibility and to direct research
      efforts towards the most promising areas. Continuing this synthesis could provide
      important insights into the evolution of traits expressed in a social context and
      the evolutionary consequences of complex and nuanced social phenotypes.

PMID- 29044797
TI  - Oxyfunctionalization of the Remote C-H Bonds of Aliphatic Amines by Decatungstate
      Photocatalysis.
AB  - Aliphatic amines, oxygenated at remote positions within the molecule, represent
      an important class of synthetic building blocks to which there are currently no
      direct means of access. Reported herein is an efficient and scalable solution
      that relies upon decatungstate photocatalysis under acidic conditions using
      either H2 O2 or O2 as the terminal oxidant. By using these reaction conditions a
      series of simple and unbiased aliphatic amine starting materials can be oxidized
      to value-added ketone products. Lastly, NMR spectroscopy using in situ LED
      irradiated samples was utilized to monitor the kinetics of the reaction, thus
      enabling direct translation of the reaction into flow.

PMID- 29044798
TI  - The impact of substance use disorders on clinical outcomes in older-adult
      psychiatric inpatients.
AB  - OBJECTIVE: To examine associations among substance use disorder (SUD) and
      measures of length of stay (LOS) and non-psychiatric medical comorbidity (MEDCO)
      in older-adult inpatients with serious mental illness (SMI), hypothesizing SUD
      would be related to worse clinical outcomes. METHODS: A cross-sectional study
      analyzed medical records from 2010 to 2016 of 7258 inpatients with SMI >= age 50,
      obtained from a 274-bed psychiatric hospital. Descriptive analyses examined
      prevalence rates for SUD status (+/-), individual drug classes, and total number
      of SUDs (polysubstance use disorders). Regression models examined the influence
      of 2 independent variables of interest: (1) SUD status (+/-) and (2) type of SUD
      (ie, specific drug), controlling for demographic factors and additional (non-SUD)
      psychiatric disorders. Two dependent (outcome) variables were examined: LOS and
      MEDCO. RESULTS: The overall SUD rate was 26%; cocaine was the most common SUD (~
      10%). SUD status and additional (non-SUD) psychiatric diagnoses were
      significantly associated with longer LOS (both P < 0.001). For individual SUDs,
      cocaine, marijuana, opiates, and alcohol were all significantly associated with
      LOS (all P < 0.01). SUD status, age, sex, admission status, and race were
      significantly associated with MEDCO (all P < 0.002). For individual SUDs,
      barbiturates, opiates, and alcohol were all significantly associated with MEDCO
      (P < 0.01). CONCLUSIONS: The prevalence of SUD in this sample underscores
      concerns related to treating older adults presenting providers with comorbid SUD
      and SMI. This combination may increase the burden and complexity of care,
      warranting further investigation into mechanisms and long-term consequences.

PMID- 29044799
TI  - Insulin secretory defect in familial partial lipodystrophy Type 2 and successful
      long-term treatment with a glucagon-like peptide 1 receptor agonist.
AB  - BACKGROUND: Familial partial lipodystrophies are rare monogenic disorders that
      are often associated with diabetes. In such cases, it can be difficult to achieve
      glycaemic control. CASE REPORT: We report a 34-year old woman with familial
      partial lipodystrophy type 2 (Dunnigan) and diabetes; her hyperglycaemia
      persisted despite metformin treatment. A combined intravenous glucose tolerance
      euglycaemic clamp test showed severe insulin resistance, as expected, but also
      showed strongly diminished first-phase insulin secretion. After the latter
      finding, we added the glucagon-like peptide-1 receptor agonist liraglutide to the
      patient's treatment regimen, which rapidly normalized plasma glucose levels.
      HbA1c values <42 mmol/mol (6.0%) have now been maintained for over 4 years.
      CONCLUSION: This case suggests that a glucagon-like peptide-1 receptor agonist
      may be a useful component of glucose-lowering therapy in individuals with
      familial partial lipodystrophy and diabetes mellitus.

PMID- 29044800
TI  - Anatomical variations of the frontal sinus and its relationship with the orbital
      cavity.
AB  - The anatomy of the frontal sinus is highly variable and its variations affect the
      occurrence/course of pathological processes. We investigated its size and
      relationship to the orbit, searching for patterns that would allow it to be
      classified anatomically. Cone beam computed tomography was applied to 91 skulls
      (age range 21-86 years) to determine sinus height, width, length, and length of
      contact with the orbit in the coronal and sagittal planes. In addition, orbital
      roof pneumatization in the coronal plane was categorized as: none; only medial
      part pneumatized; the medial and a portion of the central part pneumatized; roof
      predominantly pneumatized. Sinus dimensions varied widely (mm): height 6.2-50.0;
      width 3.7-54.0; length 2.4-45.0; frontal orbital contact 4.0-41.6; sagittal
      orbital contact 0.0-41.2. Pneumatization of the orbital roof (coronal plane)
      mostly affected the medial and a portion of the central part (50%), or the roof
      was predominantly pneumatized (32%). Three "types" of sinus (cluster analysis)
      were distinguished by the extent of pneumatization of the orbital roof in the
      coronal plane: "small", pneumatization absent or only of the medial part; "medium
      sized", pneumatization of the medial and a portion of the central part; "large",
      roof predominantly pneumatized. All dimensions were significantly different among
      the types (P < 0.001). Sinus type was fairly predictive of the extent of contact
      with the orbit in the sagittal plane (not routinely assessed clinically). The
      data confirm the variability of frontal sinus anatomy and suggest a simple and
      straightforward classification with potential clinical relevance. Clin. Anat.
      31:576-582, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29044801
TI  - Differential physiological responses to central leptin overexpression in male and
      female rats.
AB  - Brains of females are more sensitive to the acute catabolic actions of leptin.
      However, sex differences in the long-term physiological responses to central
      leptin receptor modulation are unknown. Accordingly, we centrally delivered a
      viral vector to overexpress leptin (Leptin), a neutral leptin receptor antagonist
      (Leptin-Antagonist) or a green fluorescence protein (GFP) (Control). We examined
      chronic changes in body weight and composition in male and female rats. Females
      displayed greater and sustained responses to Leptin, whereas males rapidly lost
      physiological effects and developed leptin resistance as confirmed by lower acute
      leptin-mediated phosphorylation of signal transducer and activator of
      transcription 3 (P-STAT3). Surprisingly, despite persistent physiological
      responses, Leptin-females also exhibited reduced acute leptin-mediated P-STAT3,
      suggesting an onset of leptin resistance near time of death. In line with this
      interpretation, Leptin-females and Control-females consumed the same amount of
      food on the last day of the experiment. Both Leptin-Antagonist groups gained
      similar percentages of their initial body weight and fat mass, whereas only
      Leptin-Antagonist-females gained lean body mass. Consequently, the lean/fat mass
      ratio with Leptin-Antagonist was preserved in females and decreased in males,
      suggesting a deterioration of body composition in males. In summary, the present
      study establishes that females are more responsive to long-term central leptin
      overexpression than males and that leptin antagonism has a greater physiological
      impact in males. The hormone environment may have played a role in these
      processes; however, future studies are needed to establish whether such
      physiological responses are mediated by female or male sex hormones.

PMID- 29044802
TI  - Differential and complementary roles of medial and lateral septum in the
      orchestration of limbic oscillations and signal integration.
AB  - Anatomical differences between the medial and lateral septum have associated
      these nuclei with dissimilar functional roles and behaviours. While the medial
      septum has been implicated, predominantly, in theta rhythm generation along the
      septo-hippocampal axis, the lateral septum has mainly been investigated in the
      context of septo-hypothalamic dialogue. Recent advances suggest that medial and
      lateral septum are more closely functionally related than previously appreciated.
      Here, we explore the hypothesis that the medial septum mediates ascending septo
      hippocampal theta propagation, while the lateral septum processes a descending
      hippocampo-septal and septo-hypothalamic reinforcement signal that mediates
      navigation during motivated behaviour. The generation and propagation of theta
      rhythm are critical for the initiation of exploratory behaviour. Indeed, theta
      signal processing of medial and lateral septum nuclei may well be involved in the
      integration of spatial, rewarding and locomotor signals across different brain
      networks. We review here the structural features, anatomical connectivity and
      functional properties of the medial and lateral septum. We discuss the
      heterogeneous anatomy of the lateral septum, which is composed of diverse
      subregions with distinct ascending and descending projections, and we relate the
      physiological characteristics of septal nuclei to their functional relationships
      with the hippocampal formation, the hypothalamus and the brainstem reticular
      formation during motivated spatial navigation.

PMID- 29044803
TI  - Impact of pediatric obesity on acute asthma exacerbation in Japan.
AB  - BACKGROUND: Asthma and obesity are common health problems in children. This study
      investigated the impact of obesity on children hospitalized with acute asthma
      exacerbation. METHODS: We obtained the hospital discharge records of inpatients
      aged 3-8 years with a diagnosis of asthma using a national inpatient database in
      Japan. The patients were classified into underweight, normal weight, overweight,
      and obese groups using weight for height and body mass index for age provided by
      the World Health Organization. We compared 30-day re-admission, need for
      intensive care, mean total hospitalization costs, and length of hospital stay
      between the 4 groups using multivariable regression models. RESULTS: Overall, 38
      679 patients were identified, including 3177 underweight, 28 904 normal weight,
      3334 overweight, and 3264 obese patients. The obese group showed significantly
      higher 30-day re-admission (adjusted odds ratio, 1.26; 95% confidence interval,
      1.03-1.54) and longer length of stay (adjusted difference, 0.12 days; 95%
      confidence interval, 0.10-0.20 days) than the normal weight group. The threshold
      was a 91st percentile of weight for length or body mass index for the
      relationship with 30-day re-admission. No significant difference was observed
      between the 4 groups regarding the need for intensive care and total
      hospitalization costs. CONCLUSION: These findings demonstrated that obesity was a
      risk factor for repeated admissions caused by asthma in children, indicating the
      importance for the prevention of pediatric obesity.

PMID- 29044804
TI  - Comparison of visual receptive fields in the dorsolateral prefrontal cortex and
      ventral intraparietal area in macaques.
AB  - The concept of receptive field (RF) describes the responsiveness of neurons to
      sensory space. Neurons in the primate association cortices have long been known
      to be spatially selective but a detailed characterisation and direct comparison
      of RFs between frontal and parietal association cortices are missing. We sampled
      the RFs of a large number of neurons from two interconnected areas of the frontal
      and parietal lobes, the dorsolateral prefrontal cortex (dlPFC) and ventral
      intraparietal area (VIP), of rhesus monkeys by systematically presenting a moving
      bar during passive fixation. We found that more than half of neurons in both
      areas showed spatial selectivity. Single neurons in both areas could be assigned
      to five classes according to the spatial response patterns: few non-uniform RFs
      with multiple discrete response maxima could be dissociated from the vast
      majority of uniform RFs showing a single maximum; the latter were further
      classified into full-field and confined foveal, contralateral and ipsilateral
      RFs. Neurons in dlPFC showed a preference for the contralateral visual space and
      collectively encoded the contralateral visual hemi-field. In contrast, VIP
      neurons preferred central locations, predominantly covering the foveal visual
      space. Putative pyramidal cells with broad-spiking waveforms in PFC had smaller
      RFs than putative interneurons showing narrow-spiking waveforms, but distributed
      similarly across the visual field. In VIP, however, both putative pyramidal cells
      and interneurons had similar RFs at similar eccentricities. We provide a first,
      thorough characterisation of visual RFs in two reciprocally connected areas of a
      fronto-parietal cortical network.

PMID- 29044805
TI  - The relationship between forearm skin speed-resolved perfusion and oxygen
      saturation, and finger arterial pulsation amplitudes, as indirect measures of
      endothelial function.
AB  - OBJECTIVE: Endothelial function is important for regulating peripheral blood flow
      to meet varying metabolic demands and can be measured indirectly during vascular
      provocations. In this study, we compared the PAT finger response (EndoPAT) after
      a 5-minutes arterial occlusion to that from forearm skin comprehensive
      microcirculation analysis (EPOS). METHODS: Measurements in 16 subjects with
      varying cardiovascular risk factors were carried out concurrently with both
      methods during arterial occlusion, while forearm skin was also evaluated during
      local heating. RESULTS: Peak values for EPOS skin Perfconv and speed-resolved
      total perfusion after the release of the occlusion were significantly correlated
      to the EndoPAT RHI (rho = .68, P = .007 and rho = .60, P = .025, respectively),
      mainly due to high-speed blood flow. During local heating, EPOS skin oxygen
      saturation, SO2, was significantly correlated to RHI (rho = .62, P = .043). This
      indicates that SO2 may have diagnostic value regarding endothelial function.
      CONCLUSIONS: We have demonstrated for the first time a significant relationship
      between forearm skin microcirculatory perfusion and oxygen saturation and finger
      PAT. Both local heating and reactive hyperemia are useful skin provocations.
      Further studies are needed to understand the precise regulation mechanisms of
      blood flow and oxygenation during these tests.

PMID- 29044806
TI  - Palyno-morphological characteristics of gymnosperm flora of pakistan and its
      taxonomic implications with LM and SEM methods.
AB  - The present study is intended to assess gymnosperms pollen flora of Pakistan
      using Light Microscope (LM) and Scanning Electron Microscopy (SEM) for its
      taxonomic significance in identification of gymnosperms. Pollens of 35 gymnosperm
      species (12 genera and five families) were collected from its various
      distributional sites of gymnosperms in Pakistan. LM and SEM were used to
      investigate different palyno-morphological characteristics. Five pollen types
      (i.e., Inaperturate, Monolete, Monoporate, Vesiculate-bisaccate and Polyplicate)
      were observed. Six In equatorial view seven types of pollens were observed, in
      which ten species were sub-angular, nine species were Traingular, six species
      were Perprolate, three species were Rhomboidal, three species were semi-angular,
      two species were rectangular and two species were prolate. While five types of
      pollen were observed in polar view, in which ten species were Spheroidal, nine
      species were Angular, eight were Interlobate, six species were Circular, two
      species were Elliptic. Eighteen species has rugulate and 17 species has faveolate
      ornamentation. Eighteen species has verrucate and 17 have gemmate type
      sculpturing. The data was analysed through cluster analysis. The study showed
      that these palyno-morphological features have significance value in
      classification and identification of gymnosperms. Based on these different palyno
      morphological features, a taxonomic key was proposed for the accurate and fast
      identifications of gymnosperms from Pakistan.

PMID- 29044807
TI  - Impaired emotion processing and a reduction in trust in patients with somatic
      symptom disorder.
AB  - There is accumulating evidence for deficits in the perception and regulation of
      one's own emotions, as well as the recognition of others' emotions in somatic
      symptom disorder (SSD). However, investigations of SSD focusing on specific
      aspects of emotion processing and how these might interact are missing. We
      included 35 patients with SSD and 35 healthy controls who completed
      questionnaires on the perception and regulation of their own emotions, as well as
      experimental investigations of emotion recognition and trust. In line with
      previous studies, our results show that SSD patients in comparison to healthy
      controls have difficulties in the identification and description of own feelings
      (etap2  = .381 and etap2  = .315). Furthermore, we found that patients apply less
      cognitive reappraisal (etap2  = .185) but tend to use more expressive suppression
      (etap2  = .047). In contrast to previous studies, we found SSD patients to
      perform superior in emotion recognition, in particular for anger (d = 0.40). In
      addition, patients with SSD invested less in a trust game (d = 0.73). These
      results point to a higher sensitivity for negative emotions and less trust in
      others. Further, these findings suggest a dissociation between the ability to
      recognize one's own emotions versus others' emotions in SSD. Future interventions
      targeting emotion processing in SSD might focus on the identification of one's
      own emotions, prior to the training of emotion regulation.

PMID- 29044808
TI  - Neuroprotective Effects of Human Mesenchymal Stem Cells and Platelet-Derived
      Growth Factor on Human Retinal Ganglion Cells.
AB  - Optic neuropathies such as glaucoma occur when retinal ganglion cells (RGCs) in
      the eye are injured. Strong evidence suggests mesenchymal stem cells (MSCs) could
      be a potential therapy to protect RGCs; however, little is known regarding their
      effect on the human retina. We, therefore, investigated if human MSCs (hMSCs), or
      platelet-derived growth factor (PDGF) as produced by hMSC, could delay RGC death
      in a human retinal explant model of optic nerve injury. Our results showed hMSCs
      and the secreted growth factor PDGF-AB could substantially reduce human RGC loss
      and apoptosis following axotomy. The neuroprotective pathways AKT, ERK, and STAT3
      were activated in the retina shortly after treatments with labeling seen in the
      RGC layer. A dose dependent protective effect of PDGF-AB was observed in human
      retinal explants but protection was not as substantial as that achieved by
      culturing hMSCs on the retina surface which resulted in RGC cell counts similar
      to those immediately post dissection. These results demonstrate that hMSCs and
      PDGF have strong neuroprotective action on human RGCs and may offer a
      translatable, therapeutic strategy to reduce degenerative visual loss. Stem Cells
      2018;36:65-78.

PMID- 29044809
TI  - A New Subspecies of Oxytricha granulifera (Hypotrichia: Oxytrichidae) from
      Mexico, with Notes on its Morphogenesis and Phylogenetic Position.
AB  - The genus Oxytricha Bory de Saint-Vincent in Lamouroux, Bory de Saint-Vincent and
      Deslongchamps, 1824 comprises about 38 species distributed worldwide and has been
      considered to be a nonmonophyletic group. Based on living observations, protargol
      preparations, and a small subunit ribosomal RNA (SSU rRNA) gene sequence, we
      describe a new subspecies Oxytricha granulifera chiapasensis n. subsp. This new
      taxon is morphologically characterized by undulating membranes basically in a
      Stylonychia-pattern, six dorsal kineties, size in vivo ca. 60-120 * 20-40 MUm, 21
      30 right and 21-31 left marginal cirri, 22-29 adoral membranelles, and spherical
      cortical granules arranged in longitudinal rows on the dorsal side. In terms of
      the SSU rRNA gene sequence, the new subspecies differs from populations of O.
      granulifera from GENBANK by 7-35 nucleotides. Phylogenetic analyses showed that
      Oxytricha granulifera gene sequences were nested into three groups, with the new
      subspecies included in one of them. Oxytricha granulifera chiapasensis n. subsp.
      is different from Oxytricha granulifera granulifera Foissner and Adam, 1983 and
      Oxytricha granulifera quadricirrata Blatterer and Foissner, 1988 based on: (i)
      undulating membranes in Stylonychia-pattern, (ii) formation of a sixth dorsal
      kinety during morphogenesis, (iii) the adoral membranelles number, and (iv)
      inhabiting freshwater habitats.

PMID- 29044810
TI  - Simultaneous refinement of inaccurate local regions and overall structure in the
      CASP12 protein model refinement experiment.
AB  - Advances in protein model refinement techniques are required as diverse sources
      of protein structure information are available from low-resolution experiments or
      informatics-based computations such as cryo-EM, NMR, homology models, or
      predicted residue contacts. Given semi-reliable or incomplete structural
      information, structure quality of a protein model has to be improved by ab initio
      methods such as energy-based simulation. In this study, we describe a new
      automatic refinement server method designed to improve locally inaccurate regions
      and overall structure simultaneously. Locally inaccurate regions may occur in
      protein structures due to non-convergent or missing information in template
      structures used in homology modeling or due to intrinsic structural flexibilities
      not resolved by experimental techniques. However, such variable or dynamic
      regions often play important functional roles by participating in interactions
      with other biomolecules or in transitions between different functional states.
      The new refinement method introduced here utilizes diverse types of geometric
      operators which drive both local and global changes, and the effect of structure
      changes and relaxations are accumulated. This resulted in consistent refinement
      of both local and global structural features. Performance of this method in
      CASP12 is discussed.

PMID- 29044811
TI  - Quantitative Analysis of Self-Assembly Process of a Pd2 L4 Cage Consisting of
      Rigid Ditopic Ligands.
AB  - The self-assembly process of a Pd2 L4 cage complex consisting of rigid ditopic
      ligands, in which two 3-pyridyl groups are connected to a benzene ring through
      acetylene bonds and PdII ions was revealed by a recently developed quantitative
      analysis of self-assembly process (QASAP), with which the self-assembly process
      of coordination assemblies can be investigated by monitoring the evolution with
      time of the average composition of all the intermediates. QASAP revealed that the
      rate-determining steps of the cage formation are the intramolecular ligand
      exchanges in the final stage of the self-assembly: [Pd2 L4 Py*2 ]4+ ->[Pd2 L4
      Py*1 ]4+ +Py* and [Pd2 L4 Py*1 ]4+ ->[Pd2 L4 ]4+ +Py* (Py*: 3-chloropyridine,
      which was used as a leaving ligand on the metal source). The energy barriers for
      the two reactions were determined to be 22.3 and 21.9 kcal mol-1 , respectively.
      DFT calculations of the transition-state (TS) structures for the two steps
      indicated that the distortion of the trigonal-bipyramidal PdII center at the TS
      geometries increases the activation free energy of the two steps.

PMID- 29044812
TI  - Roads to ruin: conservation threats to a sentinel species across an urban
      gradient.
AB  - Urbanization poses a global challenge to species conservation. This is primarily
      understood in terms of physical habitat loss, as agricultural and forested lands
      are replaced with urban infrastructure. However, aquatic habitats are also
      chemically degraded by urban development, often in the form of toxic stormwater
      runoff. Here we assess threats of urbanization to coho salmon throughout
      developed areas of the Puget Sound Basin in Washington, USA. Puget Sound coho are
      a sentinel species for freshwater communities and also a species of concern under
      the U.S. Endangered Species Act. Previous studies have demonstrated that
      stormwater runoff is unusually lethal to adult coho that return to spawn each
      year in urban watersheds. To further explore the relationship between land use
      and recurrent coho die-offs, we measured mortality rates in field surveys of 51
      spawning sites across an urban gradient. We then used spatial analyses to measure
      landscape attributes (land use and land cover, human population density,
      roadways, traffic intensity, etc.) and climatic variables (annual summer and fall
      precipitation) associated with each site. Structural equation modeling revealed a
      latent urbanization gradient that was associated with road density and traffic
      intensity, among other variables, and positively related to coho mortality.
      Across years within sites, mortality increased with summer and fall
      precipitation, but the effect of rainfall was strongest in the least developed
      areas and was essentially neutral in the most urbanized streams. We used the best
      supported structural equation model to generate a predictive mortality risk map
      for the entire Puget Sound Basin. This map indicates an ongoing and widespread
      loss of spawners across much of the Puget Sound population segment, particularly
      within the major regional north-south corridor for transportation and
      development. Our findings identify current and future urbanization-related
      threats to wild coho, and show where green infrastructure and similar clean water
      strategies could prove most useful for promoting species conservation and
      recovery.

PMID- 29044813
TI  - Activated mesenchymal stem cell administration inhibits chronic alcohol drinking
      and suppresses relapse-like drinking in high-alcohol drinker rats.
AB  - Neuroinflammation has been reported to follow chronic ethanol intake and may
      perpetuate alcohol consumption. Present studies determined the effect of human
      mesenchymal stem cells (hMSCs), known for their anti-inflammatory action, on
      chronic ethanol intake and relapse-like ethanol intake in a post-deprivation
      condition. Rats were allowed 12-17 weeks of chronic voluntary ethanol (10% and
      20% v/v) intake, after which a single dose of activated hMSCs (5 * 105 ) was
      injected into a brain lateral ventricle. Control animals were administered
      vehicle. After assessing the effect of hMSCs on chronic ethanol intake for 1
      week, animals were deprived of ethanol for 2 weeks and thereafter an ethanol re
      access of 60 min was allowed to determine relapse-like intake. A single
      administration of activated hMSCs inhibited chronic alcohol consumption by 70% (P
      < 0.001), an effect seen within the first 24 hours of hMSCs administration, and
      reduced relapse-like drinking by 80% (P < 0.001). In the relapse-like condition,
      control animals attain blood ethanol ('binge-like') levels >80 mg/dl. The single
      hMSC administration reduced relapse-like blood ethanol levels to 20 mg/dl.
      Chronic ethanol intake increased by 250% (P < 0.001) the levels of reactive
      oxygen species in hippocampus, which were markedly reduced by hMSC
      administration. Astrocyte glial acidic fibrillary protein immunoreactivity, a
      hallmark of neuroinflammation, was increased by 60-80% (P < 0.001) by chronic
      ethanol intake, an effect that was fully abolished by the administration of
      hMSCs. This study supports the neuroinflammation-chronic ethanol intake
      hypothesis and suggest that mesenchymal stem cell administration may be
      considered in the treatment of alcohol use disorders.

PMID- 29044814
TI  - Determination of the optimal depth of a left internal jugular venous catheter in
      infants: A prospective observational study.
AB  - BACKGROUND: Few reports exist regarding the optimal depth of a left-sided central
      venous catheter in pediatric patients. We aimed to provide a guideline for the
      optimal depth of central venous catheters at the left internal jugular vein in
      infants, using anatomical landmarks, age, height, and weight. METHODS: A two
      stage study was conducted. In the first observational study, infants aged <=1
      year and scheduled for elective surgery requiring a central venous catheter were
      enrolled. The tip of the central venous catheter was confirmed using
      transthoracic echocardiography. Linear regression modeling was performed to
      determine the association between the insertion depth of the central venous
      catheter and the I-A-B distance (I, the insertion point; A, the sternal head of
      the left clavicle; B, the midpoint of the perpendicular line drawn between the
      sternal head of the right clavicle and an imaginary line between the nipples),
      based on age, height, and weight. In the second study, the results of the first
      study were validated in another group of consecutive infants. RESULTS: In the
      first study, the data of 67 patients were analyzed. The infant's height and I-A-B
      distance were highly correlated with the level of the central venous catheter tip
      (R2 =0.763 and 0.772, respectively; all P < .01), using the regression equations
      0.11 *  height (cm) + 0.19 and 1.02 *  I-A-B (cm) + 1.55, respectively. In the
      second study, height was also highly correlated with the insertion depth of the
      central venous catheter in another 42 infants (r = .938, P = <.001). In a Bland
      Altman's analysis, the mean bias and precision of the actual insertion depth and
      predicted depth using height were 0.09 and 0.15 cm, respectively. The limits of
      agreement were -0.19 and 0.38 cm, respectively. CONCLUSION: In infants, the
      optimal depth of a central venous catheter at the left internal jugular vein can
      be determined with a simple formula using height.

PMID- 29044815
TI  - Fifty shades of green.

PMID- 29044816
TI  - Zinc-Catalyzed Hydrosilylation Copolymerization of Aromatic Dialdehydes with
      Diphenylsilane.
AB  - The hydrosilylation reaction of diphenylsilane and phthalaldehyde is catalyzed by
      heteroscorpionate zinc hydride complex LZnH (1, L = (Me Pz)2 CP(Ph)2 NPh, Me Pz =
      3,5-dimethylpyrazolyl). Both terephthalaldehyde (tPAA) and isophthalaldehyde
      (iPAA) affords linear polymer; however, when PAA is used, a seven-membered cyclic
      silyl ether is formed. These products are characterized by 1 H and 13 C NMR
      spectra. Other properties of polymers are determined by gel permeation
      chromatography (GPC)-multiangle laser-light scattering, differential scanning
      calorimetry, and thermogravimetry.

PMID- 29044817
TI  - Public health measures for pertussis prevention and control.

PMID- 29044818
TI  - Possible glimpses into early speciation: the effect of ovarian fluid on sperm
      velocity accords with post-copulatory isolation between two guppy populations.
AB  - Identifying mechanisms of reproductive isolation is key to understanding
      speciation. Among the putative mechanisms underlying reproductive isolation,
      sperm-female interactions (post-mating-prezygotic barriers) are arguably the
      hardest to identify, not least because these are likely to operate at the
      cellular or molecular level. Yet sperm-female interactions offer great potential
      to prevent the transfer of genetic information between different populations at
      the initial stages of speciation. Here, we provide a preliminary test for the
      presence of a putative post-mating-prezygotic barrier operating between three
      populations of Trinidadian guppies (Poecilia reticulata), an internally
      fertilizing fish that inhabits streams with different levels of connectivity
      across Trinidad. We experimentally evaluate the effect of female ovarian fluid on
      sperm velocity (a predictor of competitive fertilization success) according to
      whether males and females were from the same (native) or different (foreign)
      populations. Our results reveal the potential for ovarian fluid to act as a post
      mating-prezygotic barrier between two populations from different drainages, but
      also that the strength of this barrier is different among populations. This
      result may explain the previous finding that, in some populations, sperm from
      native males have precedence over foreign sperm, which could eventually lead to
      reproductive isolation between these populations.

PMID- 29044819
TI  - Repeated sleep-quality assessment and use of sleep-promoting interventions in
      ICU.
AB  - To describe sleep quality using repeated subjective assessment and the ongoing
      use of sleep-promoting interventions in intensive care. It is well known that the
      critically ill experience sleep disruption while receiving treatment in the
      intensive care unit. Both the measurement and promotion of sleep is challenging
      in the complex environment of intensive care unit. Repeated subjective assessment
      of patients' sleep in the intensive care unit and use of sleep-promoting
      interventions has not been widely reported. An observational study was conducted
      in a 58-bed adult intensive care unit. Sleep quality was assessed using the
      Richards-Campbell Sleep Questionnaire (RCSQ) each morning. intensive care unit
      audit sleep-promoting intervention data were compared to data obtained prior to
      the implementation of a sleep guideline. Patients answered open-ended questions
      about the facilitators and deterrents of their sleep in intensive care unit. The
      sample (n = 50) was predominately male (76%) with a mean age: 62.6+/-16.9 years.
      Sleep quality was assessed on 2 days or more for 21 patients. The majority of
      patients (98%) received sleep-promoting interventions. Sleep quality had not
      improved significantly since the guideline was first implemented. The mean
      Richards-Campbell Sleep Questionnaire score was 47.9+/-24.1 mm. The main sleep
      deterrents were discomfort and noise. Frequently cited facilitators were nothing
      (i.e. nothing helped) and analgesia. The Richards-Campbell Sleep Questionnaire
      was used on repeated occasions, and sleep-promoting interventions were used
      extensively. There was no evidence of improvement in sleep quality since the
      implementation of a sleep guideline. The use of the Richards-Campbell Sleep
      Questionnaire for the subjective self-assessment of sleep quality in intensive
      care unit patients and the implementation of simple-promoting interventions by
      intensive care unit clinicians is both feasible and may be the most practical way
      to assess sleep in the intensive care unit context.

PMID- 29044820
TI  - Will fluctuations in salt marsh-mangrove dominance alter vulnerability of a
      subtropical wetland to sea-level rise?
AB  - To avoid submergence during sea-level rise, coastal wetlands build soil surfaces
      vertically through accumulation of inorganic sediment and organic matter. At
      climatic boundaries where mangroves are expanding and replacing salt marsh,
      wetland capacity to respond to sea-level rise may change. To compare how well
      mangroves and salt marshes accommodate sea-level rise, we conducted a
      manipulative field experiment in a subtropical plant community in the subsiding
      Mississippi River Delta. Experimental plots were established in spatially
      equivalent positions along creek banks in monospecific stands of Spartina
      alterniflora (smooth cordgrass) or Avicennia germinans (black mangrove) and in
      mixed stands containing both species. To examine the effect of disturbance on
      elevation dynamics, vegetation in half of the plots was subjected to freezing
      (mangrove) or wrack burial (salt marsh), which caused shoot mortality. Vertical
      soil development was monitored for 6 years with the surface elevation table
      marker horizon system. Comparison of land movement with relative sea-level rise
      showed that this plant community was experiencing an elevation deficit (i.e., sea
      level was rising faster than the wetland was building vertically) and was relying
      on elevation capital (i.e., relative position in the tidal frame) to survive.
      Although Avicennia plots had more elevation capital, suggesting longer survival,
      than Spartina or mixed plots, vegetation type had no effect on rates of
      accretion, vertical movement in root and sub-root zones, or net elevation change.
      Thus, these salt marsh and mangrove assemblages were accreting sediment and
      building vertically at equivalent rates. Small-scale disturbance of the plant
      canopy also had no effect on elevation trajectories-contrary to work in peat
      forming wetlands showing elevation responses to changes in plant productivity.
      The findings indicate that in this deltaic setting with strong physical
      influences controlling elevation (sediment accretion, subsidence), mangrove
      replacement of salt marsh, with or without disturbance, will not necessarily
      alter vulnerability to sea-level rise.

PMID- 29044821
TI  - What do children observe and learn from televised sports betting advertisements?
      A qualitative study among Australian children.
AB  - OBJECTIVE: To explore children's awareness of sports betting advertising and how
      this advertising may influence children's attitudes, product knowledge and desire
      to try sports betting. METHODS: Semi-structured qualitative interviews were
      conducted with 48 children (8-16 years) from Melbourne, Victoria. The interview
      schedule explored children's recall and interpretations of sports betting
      advertising, strategies within advertisements that may appeal to children,
      children's product knowledge and understanding of betting terminology, and
      factors that may encourage gambling. Interviews were transcribed and thematic
      analysis was conducted. RESULTS: Children recalled in detail sports betting
      advertisements that they had seen, with humour the most engaging appeal strategy.
      They were also able to describe other specific appeal strategies and link these
      strategies to betting brands. Many children described how advertisements
      demonstrated how someone would place a bet, with some children recalling the
      detailed technical language associated with betting. CONCLUSIONS: Children had
      detailed recall of sports betting advertisements and an extensive knowledge of
      sports betting products and terminology. Implications for public health: To
      protect children from the potential harms associated with sports betting,
      governments should consider changing regulations and implementing evidence-based
      education campaigns to counter the positive messages children receive from the
      sports betting industry.

PMID- 29044822
TI  - First Structure of a Designed Minor Groove Binding Heterocyclic Cation that
      Specifically Recognizes Mixed DNA Base Pair Sequences.
AB  - The high-resolution NMR structure of the first heterocyclic, non-amide, organic
      cation that strongly and selectively recognizes mixed AT/GC bp (bp=base pair)
      sequences of DNA in a 1:1 complex is described. Compound designs of this type
      provide essential methods for control of functional, non-genomic DNA sequences
      and have broad cell uptake capability, based on studies from animals to humans.
      The high-resolution structural studies described in this report are essential for
      understanding the molecular basis for the sequence-specific binding as well as
      for new ideas for additional compound designs for sequence-specific recognition.
      The molecular features, in this report, explain the mechanism of recognition of
      both A?T and G?C bps and are an interesting molecular recognition story.
      Examination of the experimental structure and the NMR restrained molecular
      dynamics model suggests that recognition of the G?C base pair involves two
      specific H-bonds. The structure illustrates a wealth of information on different
      DNA interactions and illustrates an interfacial water molecule that is a key
      component of the complex.

PMID- 29044823
TI  - The many characters of visual alpha oscillations.
AB  - A central feature of human brain activity is the alpha rhythm: a 7-13 Hz
      oscillation observed most notably over occipitoparietal brain regions during
      periods of eyes-closed rest. Alpha oscillations covary with changes in visual
      processing and have been associated with a broad range of neurocognitive
      functions. In this article, we review these associations and suggest that alpha
      oscillations can be thought to exhibit at least five distinct 'characters': those
      of the inhibitor, perceiver, predictor, communicator and stabiliser. In short,
      while alpha oscillations are strongly associated with reductions in visual
      attention, they also appear to play important roles in regulating the timing and
      temporal resolution of perception. Furthermore, alpha oscillations are strongly
      associated with top-down control and may facilitate transmission of predictions
      to visual cortex. This is in addition to promoting communication between frontal
      and posterior brain regions more generally, as well as maintaining ongoing
      perceptual states. We discuss why alpha oscillations might associate with such a
      broad range of cognitive functions and suggest ways in which these diverse
      associations can be studied experimentally.

PMID- 29044824
TI  - Replication Protein A-1 Has a Preference for the Telomeric G-rich Sequence in
      Trypanosoma cruzi.
AB  - Replication protein A (RPA), the major eukaryotic single-stranded binding
      protein, is a heterotrimeric complex formed by RPA-1, RPA-2, and RPA-3. RPA is a
      fundamental player in replication, repair, recombination, and checkpoint
      signaling. In addition, increasing evidences have been adding functions to RPA in
      telomere maintenance, such as interaction with telomerase to facilitate its
      activity and also involvement in telomere capping in some conditions. Trypanosoma
      cruzi, the etiological agent of Chagas disease is a protozoa parasite that
      appears early in the evolution of eukaryotes. Recently, we have showed that T.
      cruziRPA presents canonical functions being involved with DNA replication and DNA
      damage response. Here, we found by FISH/IF assays that T. cruziRPA localizes at
      telomeres even outside replication (S) phase. In vitro analysis showed that one
      telomeric repeat is sufficient to bind RPA-1. Telomeric DNA induces different
      secondary structural modifications on RPA-1 in comparison with other types of
      DNA. In addition, RPA-1 presents a higher affinity for telomeric sequence
      compared to randomic sequence, suggesting that RPA may play specific roles in T.
      cruzi telomeric region.

PMID- 29044825
TI  - Pattern of bleeding in a large prospective cohort of haemophilia A patients: A
      three-year follow-up of the AHEAD (Advate in HaEmophilia A outcome Database)
      study.
AB  - INTRODUCTION: Outcome data on treatment of patients with haemophilia A spanning
      several years of real-world evidence collection are currently very limited. AIM
      AND METHODS: The global prospective long-term Advate(r) Haemophilia A Outcome
      Database (AHEAD) cohort study collects real-world data from patients with severe
      and moderate haemophilia. We report an interim data read-out after three years of
      observation. RESULTS: A total of 522 patients were enrolled from 21 countries:
      334 completed year 1 follow-up, 238 completed year 2 and 136 completed year 3,
      with an overall follow-up of 811 patient-years. Median annual bleeding rates
      (ABR) were 1.7 in the prophylaxis group and 8.9 in the on-demand group at year 1
      visit, 1.6 and 13.0, respectively, at year 2 visit and 2.2 and 10.3,
      respectively, at year 3 visit. Moreover, about 42% of patients on prophylaxis vs
      12% of patients on on-demand had zero annual joint bleeding rates (AJBR).
      Effectiveness of prophylaxis and on-demand treatment was deemed excellent/good in
      the majority of cases. Octocog alfa (Advate(r) ) was well tolerated. The
      inhibitors that developed in nine patients all disappeared spontaneously. Three
      patients had been previously exposed to FVIII for <=50 exposure days (EDs), 3 for
      >50 EDs and 3 showed a borderline positive inhibitory activity (<=0.6 BU/mL).
      CONCLUSIONS: These data confirm that the goal of zero bleeds is achievable,
      although not yet achieved in all patients. Understanding reasons behind the lower
      response to standard prophylaxis regimens in some patients and personalizing
      prophylactic treatment may further improve outcome in patients with haemophilia
      A.

PMID- 29044826
TI  - Implementation and evaluation of the Victorian Suicide Register.
AB  - OBJECTIVE: The Victorian Suicide Register (VSR) is a state-based suicide
      surveillance system that contains detailed information on people who die by
      suicide and the circumstances surrounding their death. In this paper, we provide
      an overview of the VSR and then describe the evaluation, which used the Centres
      for Disease Control and Prevention guidelines for surveillance system evaluation
      as a framework. METHODS: The evaluation drew on three data sources to assess
      whether the VSR: i) embodies the attributes of a good public health surveillance
      system; and ii) can be used to inform community-based suicide prevention efforts.
      RESULTS: There was a high level of acceptability and enthusiasm for having an
      accessible data collection that can stimulate local action on suicide prevention
      planning. One of the key challenges identified was data quality, particularly
      around those data collected in the course of death investigations that are not
      designed for surveillance purposes. CONCLUSION: The VSR fills an important gap in
      the sustained and systematic collection of comprehensive information on suicide,
      with some key challenges identified. Implications for public health: Findings
      from the evaluation provide important strategic information for national and
      international jurisdictions seeking to establish their own suicide registers.

PMID- 29044828
TI  - Fracture Resistance of Monolithic Glass-Ceramics Versus Bilayered Zirconia-Based
      Restorations.
AB  - PURPOSE: To compare the fracture resistance of monolithic reinforced glass
      ceramic restorations with bilayer zirconia-based restorations. MATERIALS AND
      METHODS: Fifteen ceramic crowns were fabricated on epoxy dies duplicated from a
      stainless steel master die. They were divided into 3 equal groups (n = 5)
      according to the type of ceramic material used: group I, monolithic lithium
      disilicate (IPS e.max CAD), group V, monolithic zirconia-reinforced lithium
      silicate (Vita Suprinity), and group B (bilayered zirconia substructure with
      veneering ceramic). All specimens were cemented on epoxy dies with a self
      adhesive resin cement (Rely X Unicem), subjected to a chewing simulator, and then
      loaded until fracture in a universal testing machine. The results were tabulated
      and statistically analyzed using one-way ANOVA to compare among the 3 materials.
      The Bonferroni post hoc test was used for pairwise comparisons when the ANOVA
      test was significant. RESULTS: Zirconia-reinforced lithium silicate (Vita
      Suprinity) crowns showed the highest statistically significant (p < 0.05) mean
      fracture resistance values (1742.9 +/- 102.7 N), followed by lithium disilicate
      (IPS e.max CAD) (1565.2 +/- 89.7 N). Bilayered zirconia-based crowns showed the
      lowest statistically significantly mean fracture resistance values (1267.8 +/-
      86.1 N). CONCLUSIONS: Monolithic reinforced glass-ceramics (lithium disilicate
      and zirconia-reinforced lithium silicate) have better fracture resistance than
      bilayered zirconia-based ceramics. CLINICAL IMPLICATIONS: The use of monolithic
      reinforced ceramic restorations (lithium disilicate and zirconia-reinforced
      lithium silicate) is preferred to bilayered zirconia-based restorations to avoid
      chipping of the ceramic veneer.

PMID- 29044827
TI  - Identifying the mechanism of Escherichia coli O157:H7 survival by the addition of
      salt in the treatment with organic acids.
AB  - AIM: In this study, the effects of the addition of salt to treatment with acids
      (one of several organic acids and salt in various solutions including rich or
      minimal broth, buffer, or distilled water) on the reduction of Escherichia coli
      O157:H7 were investigated. The protein expression profiles corresponding to acid
      stress (acetic acid) with or without salt addition were studied using a
      comparative proteomic analysis of E. coli O157:H7. METHODS AND RESULTS: When
      acetic, lactic, or propionic acid was combined with 3% NaCl, mutually
      antagonistic effects of acid and salt on viability of E. coli O157:H7 were
      observed only in tryptone and yeast extract broth. After exposure to acetic acid
      alone or in combination with salt, approximately 851 and 916 protein spots were
      detected, respectively. Analysis of 10 statistically significant differentially
      expressed proteins revealed that these proteins are mainly related to energy
      metabolism. CONCLUSIONS: When we compared protein expression of E. coli O157:H7
      treated with acetic acid and the combination of the acid and salt, the
      differentially expressed proteins were not related to acid stress- and salt
      stress-inducible proteins such as stress shock proteins. SIGNIFICANCE AND IMPACT
      OF THE STUDY: According to these results, the increased resistance of E. coli
      O157:H7 to acetic acid after the addition of salt may not be the result of
      synthesis of proteins related to these phenomena; therefore, further research
      needs to be conducted to identify the mechanism of the mutually antagonistic
      effect of some organic acids and salt.

PMID- 29044829
TI  - Enzyme replacement therapy prevents loss of bone and fat mass in murine
      homocystinuria.
AB  - Skeletal and connective tissue defects are the most striking symptoms in patients
      suffering from classical homocystinuria (HCU). Here, we determined body
      composition and bone mass in three mouse models of HCU and assessed whether a
      long-term administration of enzyme replacement therapy (ERT) corrected the
      phenotype. The mouse models of HCU were analyzed using dual-energy X-ray
      absorptiometry and the data were complemented by plasma biochemical profiles.
      Both the mouse model lacking CBS (KO) and the one expressing human CBS mutant
      transgene on a mouse CBS null background (I278T) showed marked bone loss and
      decreased weight mostly due to a lower fat content compared with negative
      controls. In contrast, the HO mouse expressing the human CBS WT transgene on a
      mouse CBS null background showed no such phenotype despite similar plasma
      biochemical profile to the KO and I278T mice. More importantly, administration of
      ERT rescued bone mass and changes in body composition in the KO mice treated
      since birth and reversed bone loss and improved fat content in the I278T mice
      injected after the development of clinical symptoms. Our study suggests that ERT
      for HCU may represent an effective way of preventing the skeletal problems in
      patients without a restricted dietary regime.

PMID- 29044830
TI  - Optimal management of apparatus dead space in the anesthetized infant.
AB  - Mechanical ventilation of the anesthetized infant requires careful attention to
      equipment and ventilator settings to assure optimal gas exchange and minimize the
      potential for lung injury. Apparatus dead space, defined as dead space resulting
      from devices placed between the endotracheal tube and the Y-piece of the
      breathing circuit, is the primary source of dead space controlled by the
      clinician. Due to the small tidal volumes required by infants and neonates, it is
      easy to create excessive apparatus dead space resulting in unintended hypercarbia
      or increased minute ventilation in an effort to achieve a desirable PCO2 . The
      goal of this review was to evaluate the apparatus that are commonly added to the
      breathing circuit during anesthesia care, and develop recommendations to guide
      the clinician in selecting apparatus that are best matched to the clinical goals
      and the patient's size. We include specific recommendations for apparatus that
      are best suited for different size pediatric patients, with a particular focus on
      patients <5 kg.

PMID- 29044831
TI  - A cluster of scedosporiosis in lung transplant candidates and recipients: The
      Zurich experience and review of the literature.
AB  - Scedosporium species are fungal pathogens increasingly recognized in cystic
      fibrosis (CF). They can cause multiresistant, life-threatening infections that
      are of particular concern in CF patients undergoing lung transplantation, as
      optimal treatment remains unclear. Here, we describe our Zurich experience of CF
      patients with Scedosporium infection. Disseminated infection occurred in one
      patient after transplantation and was successfully treated. We propose a step-by
      step approach to treat candidates with colonization, and discuss our cases in the
      context of the current literature.

PMID- 29044832
TI  - Understanding acceptability of and engagement with Web-based interventions aiming
      to improve quality of life in cancer survivors: A synthesis of current research.
AB  - OBJECTIVE: This review sought to summarize existing knowledge to inform the
      development of an online intervention that aims to improve quality of life after
      cancer treatment. METHODS: To inform our intervention, we searched for studies
      relating to Web-based interventions designed to improve quality of life in adults
      who have completed primary treatment for breast, prostate, and colorectal cancer
      (as these are 3 of the most common cancers and impact a large number of cancer
      survivors). We included a variety of study designs (qualitative research,
      feasibility/pilot trials, randomized trials, and process evaluations) and
      extracted all available information regarding intervention characteristics,
      experiences, and outcomes. Data were synthesized as textual (qualitative) data
      and analyzed by using thematic analysis. RESULTS: Fifty-seven full text articles
      were assessed for eligibility, and 16 papers describing 9 interventions were
      analyzed. Our findings suggest that cancer survivors value interventions that
      offer content specific to their changing needs and are delivered at the right
      stage of the cancer trajectory. Social networking features do not always provide
      added benefit, and behavior change techniques need to be implemented carefully to
      avoid potential negative consequences for some users. CONCLUSIONS: Future work
      should aim to identify appropriate strategies for promoting health behavior
      change, as well as the optimal stage of cancer survivorship to facilitate
      intervention delivery. CLINICAL IMPLICATIONS: The development of Web-based
      interventions for cancer survivors requires further exploration to better
      understand how interventions can be carefully designed to match this group's
      unique needs and capabilities. User involvement during development may help to
      ensure that interventions are accessible, perceived as useful, and appropriate
      for challenges faced at different stages of the cancer survivorship trajectory.

PMID- 29044833
TI  - Lateral Graphene-Contacted Vertically Stacked WS2 /MoS2 Hybrid Photodetectors
      with Large Gain.
AB  - A demonstration is presented of how significant improvements in all-2D
      photodetectors can be achieved by exploiting the type-II band alignment of
      vertically stacked WS2 /MoS2 semiconducting heterobilayers and finite density of
      states of graphene electrodes. The photoresponsivity of WS2 /MoS2 heterobilayer
      devices is increased by more than an order of magnitude compared to homobilayer
      devices and two orders of magnitude compared to monolayer devices of WS2 and MoS2
      , reaching 103 A W-1 under an illumination power density of 1.7 * 102 mW cm-2 .
      The massive improvement in performance is due to the strong Coulomb interaction
      between WS2 and MoS2 layers. The efficient charge transfer at the WS2 /MoS2
      heterointerface and long trapping time of photogenerated charges contribute to
      the observed large photoconductive gain of ~3 * 104 . Laterally spaced graphene
      electrodes with vertically stacked 2D van der Waals heterostructures are employed
      for making high-performing ultrathin photodetectors.

PMID- 29044834
TI  - Confinement of Water Pentamers within the Crystals of a Reduced Cyclotribenzoin.
AB  - Reduction of cyclotribenzoin with sodium borohydride produces a cone-shaped
      hexaol. Crystals of this hexaol, obtained from wet tetrahydrofuran, encapsulate
      clusters of five water molecules in an idealized hydrogen-bonded arrangement. The
      water pentamer is stabilized by hydrogen bonding with the -OH groups of the
      hexaol, and [O-H???pi] interactions with the benzene rings of the reduced
      cyclotribenzoin.

PMID- 29044835
TI  - Screening and referral for children with physical disabilities.
AB  - The clinical care of children with physical disabilities is a major priority for
      paediatricians and paediatric orthopaedic surgeons. Cerebral palsy (CP) is the
      prototypical condition and remains the most common cause of physical disability
      in developed countries. The incidence is approximately 2 per 1000 live births,
      translating to between 600 and 700 new children per annum in Australia, with
      approximately 34 000 children and adults currently living with CP. This figure is
      predicted to rise inexorably over the next 20 years. The care of children with
      physical disabilities, including those with CP, is usually coordinated by
      paediatricians, general practitioners and allied health teams including
      physiotherapists, with input from paediatric orthopaedic surgeons when
      appropriate. The emphasis in care for children with CP has moved from 'reactive'
      to 'proactive'. In the past, children are often referred when symptomatic, for
      example when a hip dislocation had occurred and became painful. The emphasis now
      is on coordinated, multidisciplinary care in which musculoskeletal manifestations
      of disability are identified by screening programmes. Systematic screening,
      especially when population-based and linked to a register, avoids children
      getting 'lost in the system'. Early and more effective interventions may be
      offered for the prevention of contractures, dislocation of the hip and spinal
      deformities. In this review, we will focus on the assessment of gait in children
      with physical disabilities, and monitoring for hip and spine deformity.

PMID- 29044836
TI  - Postpartum depressive symptoms and their association with social support among
      foreign mothers in Japan at 3 to 4 months postpartum.
AB  - BACKGROUNDS: With Japan's globalization, maternal-child health care for foreign
      mothers is highly necessary. We examined postpartum depressive symptoms in
      foreign mothers in Japan and the factors associated with such symptoms,
      particularly social support. METHOD: A cross-sectional study was conducted for
      Japanese and foreign mothers at 3 to 4 months postpartum. The Edinburgh Postnatal
      Depression Scale was used to evaluate postpartum depression symptom, and social
      support was evaluated by support type and provider. Multiple regression analyses
      was used. RESULTS: Data from 97 Japanese mothers and 68 foreign mothers were
      analyzed. The average score of Edinburgh Postnatal Depression Scale for foreign
      mothers was 7.5, significantly higher than that for Japanese mothers (4.2).
      Financial circumstances, spouse-partners' emotional support, and families'
      informational support were significantly related to foreign mothers' postpartum
      depressive symptoms. CONCLUSION: Postpartum depression symptoms were more common
      among foreign mothers than among Japanese mothers. Medical personnel should
      encourage such mothers to obtain more social support from their spouse-partners
      and family.

PMID- 29044837
TI  - Corrigendum.

PMID- 29044838
TI  - Evidence in a post-truth world: Nurses and critical thinking.

PMID- 29044839
TI  - Electro- and Photocatalytic Generation of H2 Using a Distinctive CoII "PN3 P"
      Pincer Supported Complex with Water or Saturated Saline as a Hydrogen Source.
AB  - Efficient electrocatalytic production of H2 from mixed water/acetonitrile
      solutions was achieved using three new CoII complexes supported by the neutral
      pincer ligand bis(diphenylphosphino)-2,6-di(methylamino)pyridine ("PN3 P"). At 
      1.9 V vs. Fc/Fc+ , these catalysts showed 96 % Faradaic efficiency with added
      water or saturated aqueous saline at rates of up to 316 L(mol cat)-1 (cm2 )-1  h
      1 using a glassy carbon working electrode. The complex [Co(kappa3 -2,6-{Ph2
      PNMe}2 (NC5 H3 )Br2 ] (1) was also able to photocatalytically reduce water to
      hydrogen in the presence of a Ru(bpy)32+ photosensitizer and a reductant.

PMID- 29044841
TI  - Multi-biomarker risk stratification in heart failure: a story of diminished
      marginal returns after Herculean efforts?

PMID- 29044840
TI  - Impacts of climate and land use on N2 O and CH4 fluxes from tropical ecosystems
      in the Mt. Kilimanjaro region, Tanzania.
AB  - In this study, we quantify the impacts of climate and land use on soil N2 O and
      CH4 fluxes from tropical forest, agroforest, arable and savanna ecosystems in
      Africa. To do so, we measured greenhouse gases (GHG) fluxes from 12 different
      ecosystems along climate and land-use gradients at Mt. Kilimanjaro, combining
      long-term in situ chamber and laboratory soil core incubation techniques. Both
      methods showed similar patterns of GHG exchange. Although there were distinct
      differences from ecosystem to ecosystem, soils generally functioned as net
      sources and sinks for N2 O and CH4 respectively. N2 O emissions correlated
      positively with soil moisture and total soil nitrogen content. CH4 uptake rates
      correlated negatively with soil moisture and clay content and positively with
      SOC. Due to moderate soil moisture contents and the dominance of nitrification in
      soil N turnover, N2 O emissions of tropical montane forests were generally low
      (<1.2 kg N ha-1  year-1 ), and it is likely that ecosystem N losses are driven
      instead by nitrate leaching (~10 kg N ha-1  year-1 ). Forest soils with well
      aerated litter layers were a significant sink for atmospheric CH4 (up to 4 kg C
      ha-1  year-1 ) regardless of low mean annual temperatures at higher elevations.
      Land-use intensification significantly increased the soil N2 O source strength
      and significantly decreased the soil CH4 sink. Compared to decreases in
      aboveground and belowground carbon stocks enhanced soil non-CO2 GHG emissions
      following land-use conversion from tropical forests to homegardens and coffee
      plantations were only a small factor in the total GHG budget. However, due to
      lower ecosystem carbon stock changes, enhanced N2 O emissions significantly
      contributed to total GHG emissions following conversion of savanna into grassland
      and particularly maize. Overall, we found that the protection and sustainable
      management of aboveground and belowground carbon and nitrogen stocks of
      agroforestry and arable systems is most crucial for mitigating GHG emissions from
      land-use change.

PMID- 29044842
TI  - Changing Perspectives on the Strategic Use of Microwave Heating in Organic
      Synthesis.
AB  - This Personal Account describes collaborative investigations into apocryphal
      microwave effects in organic chemistry. Focused research on microwave-assisted
      organic synthesis has been fraught with confusion, controversy, and
      misinformation. Microwave heating is an undoubtedly useful tactic for organic
      synthesis, but whether or not it can offer strategic advantages remains an open
      question in the minds of many people. (Ironically, those who do not consider it
      an open question are split as to whether it has been resolved affirmatively or
      negatively.) Our research in this area is guided by the hypothesis that microwave
      heating can alter reaction kinetics in ways distinct from what is observable
      under conventional heating. Here we provide a succinct record of the origins of
      our interests, our initial queries and associated controversies, and recent
      efforts to identify, quantify, and begin to leverage selective microwave heating
      for strategic advantage in organic synthesis.

PMID- 29044844
TI  - Abstracts for the 43rd Annual Meeting of the International Society for Pediatric
      and Adolescent Diabetes (ISPAD), 18-21 October 2017, Innsbruck, Austria.

PMID- 29044843
TI  - Bioorthogonal Click and Release Reaction of Iminosydnones with Cycloalkynes.
AB  - We report the discovery of a new bioorthogonal click-and-release reaction
      involving iminosydnones and strained alkynes. This transformation leads to two
      products resulting from the ligation and fragmentation of iminosydnones under
      physiological conditions. Optimized iminosydnones were successfully used to
      design innovative cleavable linkers for protein modification, thus opening up new
      areas in the fields of drug release and target-fishing applications. This click
      and-release technology offers the possibility of exchanging tags on proteins for
      functionalized cyclooctynes under mild and bioorthogonal conditions.

PMID- 29044845
TI  - ePoster Sessions.

PMID- 29044846
TI  - Socio-demographic factors drive regional differences in participation in the
      National Bowel Cancer Screening Program - An ecological analysis.
AB  - OBJECTIVE: To examine if geographic variations in the participation rates in the
      National Bowel Cancer Screening Program (NBCSP) are related to population-level
      socio-demographic characteristics. METHODS: Data reflecting participation in the
      NBCSP for 504 Local Government Areas (LGAs) between July 2011 and June 2013 were
      extracted from the Social Health Atlas of Australia. Logistic regression models
      were used to examine independent associations (odds ratios [ORs]) between
      participation, Remoteness Area (RA) and selected socio-demographic variables.
      RESULTS: Compared to the participation rate for major cities (33.4%),
      participation was significantly higher in inner regional areas (36.5%, OR=1.15),
      but was much lower in remote (27.9%, OR=0.77) or very remote areas (25.0%,
      OR=0.65). When controlling for study period, gender, proportion of persons aged
      65 years and older, Indigenous status, cultural background and socioeconomic
      status, significantly higher rates were observed in all non-metropolitan areas
      than in major cities. Indigenous status was strongly related to the poorer
      participation in remote areas. CONCLUSIONS: Socio-demographic characteristics,
      particularly Indigenous status, cultural background and population ageing, seem
      to be more important drivers of regional disparities in NBCSP participation than
      geographic remoteness. Implications for public health: This study provides
      important evidence to understand the regional disparities in participating in the
      national screening program.

PMID- 29044847
TI  - Obesity-related health impacts of active transport policies in Australia - a
      policy review and health impact modelling study.
AB  - OBJECTIVE: To review Australian policies on active transport, defined as walking
      and cycling for utilitarian purposes. To estimate the potential health impact of
      achieving four active transport policy scenarios. METHODS: A policy review was
      undertaken, using key words to search government websites. Potential health
      benefits were quantified using a cohort simulation Markov model to estimate
      obesity and transport injury-related health effects of an increase in active
      transport. Health adjusted life years (HALYs) gained and healthcare cost savings
      from diseases averted were estimated. Budget thresholds to achieve cost
      effectiveness were estimated for each scenario. RESULTS: There is broad
      recognition of the health-related benefits of active transport from all levels of
      Australian government. Modelling results suggest significant health-related
      benefits of achieving increased prevalence of active transport. Total HALYs saved
      assuming a one-year effect ranged from 565 (95%UI 173-985) to 12,105 (95%UI 4,970
      19,707), with total healthcare costs averted ranging from $6.6M (95%UI $1.9M
      11.3M) to $141.2M (95%UI $53.8M-227.8M). CONCLUSION: Effective interventions that
      improve rates of active transport may result in substantial healthcare-related
      cost savings through a decrease in conditions related to obesity. Implications
      for public health: Significant potential exists for effective and cost-effective
      interventions that result in more walking and cycling.

PMID- 29044848
TI  - A Novel Approach to Synthesise a Dual-Mode Luminescent Composite Pigment for
      Uncloneable High-Security Codes to Combat Counterfeiting.
AB  - A strategy is demonstrated to protect valuable items, such as currency,
      pharmaceuticals, important documents, etc. against counterfeiting, by marking
      them with luminescent security codes. These luminescent security codes were
      printed by employing luminescent ink formulated from a cost effective dual-mode
      luminescent composite pigment of Gd1.7 Yb0.2 Er0.1 O3 and Zn0.98 Mn0.02 S
      phosphors using commercially available PVC Gold medium. In the composite, Gd1.7
      Yb0.2 Er0.1 O3 and Zn0.98 Mn0.02 S account for upconversion and downconversion
      processes, respectively. The synthesis procedure of the composite involves the
      admixing of Gd1.7 Yb0.2 Er0.1 O3 nanorods and Zn0.98 Mn0.02 S phosphor,
      synthesised by hydrothermal and facile solid-state reaction methods,
      respectively. The structural, morphological, microstructural, and
      photoluminescent features of Gd1.7 Yb0.2 Er0.1 O3 nanorods, Zn0.98 Mn0.02 S
      phosphor and composite were characterised by using XRD, SEM, TEM, and
      photoluminescence (PL) techniques, respectively. The distribution of PL intensity
      of the printed pattern was examined by using confocal PL mapping microscopy. The
      obtained results reveal that security codes printed using ink formulated from
      this bi-luminescent composite pigment provide dual-stage security against
      counterfeiting.

PMID- 29044849
TI  - Carvacrol and eugenol effectively inhibit Rhizopus stolonifer and control
      postharvest soft rot decay in peaches.
AB  - AIMS: This study aimed to investigate the antifungal mechanism of carvacrol and
      eugenol to inhibit Rhizopus stolonifer and the control of postharvest soft rot
      decay in peaches. METHODS AND RESULTS: To investigate the antifungal mechanism,
      the effects of carvacrol and eugenol on the mycelium growth, leakages of
      cytoplasmic contents, mycelium morphology, cell membrane and membrane composition
      of R. stolonifer were studied. Carvacrol and eugenol both exhibited dose
      dependent antifungal activity against R. stolonifer, carvacrol at a concentration
      of 2 MUl per plant and eugenol at a concentration of 4 MUl per plant inhibited
      fungal growth completely. The two essential oils (EOs) increased cell membrane
      penetrability and caused the leakage of cytoplasm, nucleic acid and protein
      content. The observation using scanning electron microscopy and fluorescent
      microscopy showed modification of the hyphal morphology and breakage of the cell
      plasma membrane. Decreased ergosterol contents confirmed that the two EOs could
      destroy the membrane of R. stolonifer. For the in vivo test, the inhibition of
      soft rot disease and the induction of defence-related enzymes were investigated.
      Carvacrol and eugenol significantly reduced the incidence and severity of soft
      rot decay in inoculated peaches. The best treatments for controlling soft rot
      decay were obtained at 0.5 MUl l-1 for carvacrol and 1 MUl l-1 for eugenol. The
      activities of defence-related enzymes in peaches were also enhanced by fumigation
      with two EOs. CONCLUSION: This study showed that carvacrol and eugenol could
      effectively inhibit the growth of R. stolonifer in vitro and successfully control
      the incidence of soft rot decay in honey peaches. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The above findings may be the main antifungal mechanism of carvacrol and
      eugenol on R. stolonifer. Furthermore, carvacrol and eugenol are helpful for
      their commercial application on the preservation of fresh fruit.

PMID- 29044850
TI  - Mesenchymal stem cell therapy: A promising cell-based therapy for treatment of
      myocardial infarction.
AB  - For decades, mesenchymal stem (MSCs) cells have been used for cardiovascular
      diseases as regenerative therapy. This review is an attempt to summarize the
      types of MSCs involved in myocardial infarction (MI) therapy, as well as its
      possible mechanisms effects, especially the paracrine one in MI focusing on the
      studies (human and animal) conducted within the last 10 years. Recently, reports
      showed that MSC therapy could have infarct-limiting effects after MI in both
      experimental and clinical trials. In this context, various types of MSCs can help
      cardiac regeneration by either revitalizing the cardiac stem cells or
      revascularizing the arteries and veins of the heart. Furthermore, MSCs could
      produce paracrine growth factors that increase the survival of nearby
      cardiomyocytes, as well as increase angiogenesis through recruitment of stem cell
      from bone marrow or inducing vessel growth from existing capillaries. Recent
      research suggests that the paracrine effects of MSCs could be mediated by
      extracellular vesicles including exosomes. Exosomal microRNAs (miRNAs) released
      by MSCs are promising therapeutic hotspot target for MI. This could be attributed
      to the role of miRNA in cardiac biology, including cardiac regeneration, stem
      cell differentiation, apoptosis, neovascularization, cardiac contractility and
      cardiac remodeling. Furthermore, gene-modified MSCs could be a recent promising
      therapy for MI to enhance the paracrine effects of MSCs, including better homing
      and effective cell targeted tissue regeneration. Although MSC therapy has
      achieved considerable attention and progress, there are critical challenges that
      remains to be overcome to achieve the most effective successful cell-based
      therapy in MI.

PMID- 29044851
TI  - A Bifunctional Fluorogenic Rhodamine Probe for Proximity-Induced Bioorthogonal
      Chemistry.
AB  - Bioorthogonal reactions have emerged as a versatile tool in life sciences. The
      inverse electron demand Diels-Alder reaction (DAinv ) stands out due to the
      availability of reactants with very fast kinetics. However, highly reactive
      dienophiles suffer the disadvantage of being less stable and prone to side
      reactions. Herein, we evaluate the extent of acceleration of rather unreactive
      but highly stable dienophiles by DNA-templated proximity. To this end, we
      developed a modular synthetic route for a novel bifunctional fluorogenic
      tetrazine rhodamine probe that we used to determine the reaction kinetics of
      various dienophiles in a fluorescence assay. Under proximity-driven conditions
      the reaction was found to be several orders of magnitude faster, and we observed
      almost no background reaction when proximity was not induced. This fundamental
      study identifies a minimally sized fluorogenic tetrazine dienophile reactant pair
      that has potential to be generally used for the visualization of biomolecular
      interactions with temporal and spatial resolution in living systems.

PMID- 29044852
TI  - Firework-related injury in the Top End: a 16-year review.
AB  - BACKGROUND: On July 1st on 'Territory Day', the public in the Northern Territory
      are permitted to purchase and operate consumer fireworks without a licence.
      Serious permanent injuries from fireworks are well described, leading to their
      banning in many other jurisdictions. This study describes those seriously injured
      by fireworks in the Top End of the Northern Territory, with the aim of
      identifying opportunities for prevention and harm minimization. METHODS: This is
      a retrospective audit of all admitted patients with an injury from fireworks at
      the Royal Darwin Hospital between 2000 and 2015. The variables collected included
      demographic data and the circumstances around injury (operator versus bystander,
      alcohol involvement and day of device operation). The consequences such as
      injuries, operating theatre visits, length of stay and outpatient visits are
      described. RESULTS: Fifty-five patients (including 17 children) suffered 67
      injuries over the study period, resulting in 68 operating theatre visits, 322
      hospital days and 380 outpatient appointments. Burns, hand and eye injuries
      predominate. Females (P = 0.000) and children (P = 0.029) were more likely to be
      injured as bystanders. Injuries on a day other than Territory Day were more
      likely to have alcohol involvement (P = 0.01), and occur in the operator (P =
      0.017). CONCLUSION: Consumer firework usage results in a small number of life
      altering injuries annually. Previous prevention campaigns focusing on device user
      safety should be expanded to include the safety of bystanders and children and
      reduce firework usage outside of the Territory Day.

PMID- 29044854
TI  - Targeted proteomic analysis of habitual coffee consumption.
AB  - BACKGROUND: Coffee drinking has been implicated in mortality and a variety of
      diseases but potential mechanisms underlying these associations are unclear.
      Large-scale systems epidemiological approaches may offer novel insights to
      mechanisms underlying associations of coffee with health. OBJECTIVE: We performed
      an analysis of known and novel protein markers linked to cardiovascular disease
      and their association with habitual coffee intake in the Prospective Study of the
      Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in
      the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n =
      2418). METHODS: In PIVUS and ULSAM, coffee intake was measured by 7-day dietary
      records whilst a computer-based food frequency questionnaire was used in
      EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity
      extension assay. RESULTS: Four protein-coffee associations adjusted for age, sex,
      smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 * 10-3
      ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF)
      receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association
      between coffee intake and LEP replicated in ULSAM (beta, -0.042 SD per cup of
      coffee, P = 0.028) and EpiHealth (beta, -0.025 SD per time of coffee, P = 0.004).
      The negative coffee-CHI3L association replicated in EpiHealth (beta, -0.07, P =
      1.15 * 10-7 ), but not in ULSAM (beta, -0.034, P = 0.16). CONCLUSIONS: The
      current study supports an inverse association between coffee intake and plasma
      LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants
      further investigation given links between CHI3L1 and health conditions that are
      also potentially influenced by coffee.

PMID- 29044853
TI  - Regulation of voltage-gated potassium channels in vascular smooth muscle during
      hypertension and metabolic disorders.
AB  - Voltage-gated potassium (KV ) channels are key regulators of vascular smooth
      muscle contractility and vascular tone, and thus have major influence on the
      microcirculation. KV channels are important determinants of vascular smooth
      muscle membrane potential (Em ). A number of KV subunits are expressed in the
      plasma membrane of smooth muscle cells. Each subunit confers distinct kinetics
      and regulatory properties that allow for fine control of Em to orchestrate
      vascular tone. Modifications in KV subunit expression and/or channel activity can
      contribute to changes in vascular smooth muscle contractility in response to
      different stimuli and in diverse pathological conditions. Consistent with this, a
      number of studies suggest alterations in KV subunit expression and/or function as
      underlying contributing mechanisms for small resistance artery dysfunction in
      pathologies such as hypertension and metabolic disorders, including diabetes.
      Here, we review our current knowledge on the effects of these pathologies on KV
      channel expression and function in vascular smooth muscle cells, and the
      repercussions on (micro)vascular function.

PMID- 29044855
TI  - Annual killifishes as model systems for advancing understanding of evolution and
      developmental biology.

PMID- 29044856
TI  - Zebrafish as models for developmental disease & repair.

PMID- 29044857
TI  - Direct Synthesis of Polymer Nanotubes by Aqueous Dispersion Polymerization of a
      Cyclodextrin/Styrene Complex.
AB  - A one-step synthesis of nanotubes by RAFT dispersion polymerization of
      cyclodextrin/styrene (CD/St) complexes directly in water is presented. The
      resulted amphiphilic PEG-b-PS diblock copolymers self-assemble in situ into
      nanoparticles with various morphologies. Spheres, worms, lamellae, and nanotubes
      were controllably obtained. Because of the complexation, the swelling degree of
      polystyrene (PS) blocks by free St is limited, resulting in limited mobility of
      PS chains. Consequently, kinetically trapped lamellae and nanotubes were obtained
      instead of spherical vesicles. During the formation of nanotubes, small vesicles
      first formed at the ends of the tape-like lamellae, then grew and fused into
      nanotubes with a limited chain rearrangement. The introduction of a host-guest
      interaction based on CDs enables the aqueous dispersion polymerization of water
      immiscible monomers, and produces kinetically trapped nanostructures, which could
      be a powerful technique for nanomaterials synthesis.

PMID- 29044858
TI  - Pharmacological and chemical features of Nepeta L. genus: Its importance as a
      therapeutic agent.
AB  - Medicinal plants have always had great value for the human population due to
      their valuable constituents and potential bioactivities. The objective of this
      review is to present an updated overview of an important medicinal plant genus
      Nepeta L., from the family Lamiaceae, revealing its traditional utilization,
      biological activity, phytoconstituents, and mechanisms of action. For this
      purpose, a literature survey was carried out by using SciFinder, ScienceDirect,
      Scopus, PubMed, and Web of Science followed by a revision of the bibliographies
      of the related articles. We have described and analyzed the role of plants in
      drug discovery and the importance of Nepeta species. Information on the
      utilization purposes of Nepeta species in folk medicine has been emphasized, and
      scientific studies on the biological effects and secondary metabolites are
      addressed. Nepeta species are characterized by terpenoid-type compounds and
      phenolic constituents, which exert several activities such as an antimicrobial,
      repellent against major pathogen vector mosquitoes, insecticide, larvicide
      against Anopheles stephensi, cytotoxic anticarcinogen, antioxidant,
      anticonvulsant, analgesic, anti-inflammatory agent, and antidepressant, revealing
      its importance in medicinal and agricultural fields. On the basis of numerous
      studies, the Nepeta genus demonstrates remarkable therapeutic effects against
      various diseases. However, clinical studies are warranted to confirm preclinical
      findings.

PMID- 29044859
TI  - Testing feasibility of an accurate microscopic assessment of macrovesicular
      steatosis in liver allograft biopsies by smartphone add-on lenses.
AB  - Light microscopy is an essential tool in histological examination of tissue
      samples. However, the required equipment for a correct and rapid diagnosis is
      sometimes unavailable. Smartphones and mobile phone networks are widespread, and
      could be used for diagnostic imaging and telemedicine. Macrovesicular steatosis
      (MS) is a major risk factor for liver graft failure, and is only assessable by
      microscopic examination of a frozen tissue section. The aim of this study was to
      compare the microscopic assessment of MS in liver allograft biopsies by a
      smartphone with eyepiece adaptor (BLIPS device) to standard light microscopy.
      Forty liver graft biopsies were evaluated in transmitted light, using an Iphone
      5s and 4 different mini-objective, add-on lenses. A significant correlation was
      reported between the two different approaches for graft MS assessment (Spearman's
      correlation coefficient: rs  = 0.946; p < .001). Smartphone with eyepiece adaptor
      had similar discriminatory power to identify MS in liver grafts than standard
      light microscopy. Based on these findings, a smartphone integrated with a low
      cost eyepiece adaptor can achieve adequate accuracy in the assessment of MS in
      liver graft, and could be used as an alternative to standard light microscope
      when unavailable.

PMID- 29044860
TI  - Effects of exenatide twice daily, exenatide once weekly or insulin in patients
      with type 2 diabetes and baseline HbA1c >=10.0%: Two pooled analyses including 20
      randomised controlled trials.
AB  - AIMS: Patients with advanced type 2 diabetes (T2D) and high glycated haemoglobin
      (HbA1c) values can be difficult to treat because of their severe metabolic
      disease. This pooled analysis examined the treatment effects of exenatide twice
      daily (BID), exenatide once weekly (QW) and insulin in patients with high
      baseline HbA1c (>=10.0%). METHODS: This post hoc analysis used pooled data from
      12 and 8 randomised controlled trials of exenatide BID and exenatide QW,
      respectively. Patients with T2D who completed at least 24 weeks of treatment with
      exenatide BID, exenatide QW or insulin (insulin glargine, insulin detemir or
      insulin aspart) were categorised by baseline HbA1c. Patients with HbA1c >=10.0%
      were included in the analysis. RESULTS: Both exenatide and insulin reduced HbA1c
      (mean +/- SE reduction: -2.0% +/- 0.2% [exenatide] and -2.1% +/- 0.2% [insulin]
      in the exenatide BID studies, and -2.6% +/- 0.1% [exenatide] and -2.1% +/- 0.2%
      [insulin] in the exenatide QW studies; all P < .001). Body weight decreased with
      exenatide and increased with insulin. Systolic blood pressure decreased with
      exenatide QW. Insulin dose increased over the course of treatment. The most
      common adverse events with exenatide were gastrointestinal. Insulin was
      associated with some hypoglycaemia risk. Hypoglycaemia events occurred
      infrequently with exenatide when given without sulphonylureas. CONCLUSIONS: For
      patients with high HbA1c, treatment with exenatide or insulin both improved
      glycaemic control. Given the associated weight loss and low risk of
      hypoglycaemia, exenatide may be a suitable alternative to treatment with insulin
      in certain patients with T2D and high HbA1c.

PMID- 29044861
TI  - Comparison of bleeding risk scores in patients with atrial fibrillation: insights
      from the RE-LY trial.
AB  - BACKGROUND: Oral anticoagulation is the mainstay of stroke prevention in atrial
      fibrillation (AF), but must be balanced against the associated bleeding risk.
      Several risk scores have been proposed for prediction of bleeding events in
      patients with AF. OBJECTIVES: To compare the performance of contemporary clinical
      bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg,
      150 mg or warfarin in the RE-LY trial. METHODS: HAS-BLED, ORBIT, ATRIA and
      HEMORR2 HAGES bleeding risk scores were calculated based on clinical information
      at baseline. All major bleeding events were centrally adjudicated. RESULTS: There
      were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years.
      For all the four schemes, high-risk subgroups had higher risk of major bleeding
      (all P < 0.001). The ORBIT score showed the best discrimination with c-indices of
      0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial
      bleeding, which were significantly better than for the HAS-BLED score (difference
      in c-indices: 0.050, 0.053 and 0.048, respectively, all P < 0.05). The ORBIT
      score also showed the best calibration compared with previous data. Significant
      treatment interactions between the bleeding scores and the risk of major bleeding
      with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P = 0.0019),
      ATRIA (P < 0.001) and HEMORR2 HAGES (P < 0.001) scores. HAS-BLED score showed a
      nonsignificant trend for interaction (P = 0.0607). CONCLUSIONS: Amongst the
      current clinical bleeding risk scores, the ORBIT score demonstrated the best
      discrimination and calibration. All the scores demonstrated, to a variable
      extent, an interaction with bleeding risk associated with dabigatran or warfarin.

PMID- 29044862
TI  - Efficacy and safety of vinorelbine plus cisplatin chemotherapy for patients with
      recurrent and/or metastatic salivary gland cancer of the head and neck.
AB  - BACKGROUND: The purpose of this study was to investigate the efficacy and safety
      of vinorelbine plus cisplatin chemotherapy in patients with recurrent and/or
      metastatic salivary gland cancer of the head and neck. METHODS: In this single
      arm phase II study, patients with recurrent and/or metastatic salivary gland
      cancer were treated with i.v. vinorelbine (25 mg/m2 ) on days 1 and 8 plus
      cisplatin (80 mg/m2 ) on day 1 every 3 weeks for 4 or 6 cycles. The primary
      endpoint was the objective response rate. Progression-free survival (PFS),
      overall survival (OS), and adverse events were also assessed. RESULTS: Between
      September 2008 and November 2014, 40 patients with recurrent and/or metastatic
      salivary gland cancer received vinorelbine plus cisplatin chemotherapy. The
      objective response rate was 35.0%, including 1 complete response. Median PFS and
      OS rates were 6.3 months and 16.9 months, respectively. No treatment-related
      deaths occurred. CONCLUSION: Administering vinorelbine plus cisplatin
      chemotherapy to patients with recurrent and/or metastatic salivary gland cancers
      is safe and effective.

PMID- 29044864
TI  - Experimental Proof of the Bifunctional Mechanism for the Hydrogen Oxidation in
      Alkaline Media.
AB  - Realization of the hydrogen economy relies on effective hydrogen production,
      storage, and utilization. The slow kinetics of hydrogen evolution and oxidation
      reaction (HER/HOR) in alkaline media limits many practical applications involving
      hydrogen generation and utilization, and how to overcome this fundamental
      limitation remains debatable. Here we present a kinetic study of the HOR on
      representative catalytic systems in alkaline media. Electrochemical measurements
      show that the HOR rate of Pt-Ru/C and Ru/C systems is decoupled to their hydrogen
      binding energy (HBE), challenging the current prevailing HBE mechanism. The
      alternative bifunctional mechanism is verified by combined electrochemical and in
      situ spectroscopic data, which provide convincing evidence for the presence of
      hydroxy groups on surface Ru sites in the HOR potential region and its key role
      in promoting the rate-determining Volmer step. The conclusion presents important
      references for design and selection of HOR catalysts.

PMID- 29044863
TI  - Identification of somatic genetic alterations in ovarian clear cell carcinoma
      with next generation sequencing.
AB  - Ovarian clear cell carcinoma (OCCC) is the most refractory subtype of ovarian
      cancer and more prevalent in Japanese than Caucasians (25% and 5% of all ovarian
      cancer, respectively). The aim of this study is to discover the genomic
      alterations that may cause OCCC and effective molecular targets for chemotherapy.
      Paired genomic DNAs of 48 OCCC tissues and corresponding noncancerous tissues
      were extracted from formalin-fixed, paraffin embedded specimens collected between
      2007 and 2015 at Tohoku University Hospital. All specimens underwent exome
      sequencing and the somatic genetic alterations were identified. We divided the
      cases into three clusters based on the mutation spectra. Clinical characteristics
      such as age of onset and endometriosis are similar among the clusters but one
      cluster shows mutations related to APOBEC activation, indicating its contribution
      to subset of OCCC cases. There are three hypermutated cases (showing 12-fold or
      higher somatic mutations than the other 45 cases) and they have germline and
      somatic mismatch repair gene alterations. The frequently mutated genes are ARID1A
      (66.7%), PIK3CA (50%), PPP2R1A (18.8%), and KRAS (16.7%). Somatic mutations
      important for selection of chemotherapeutic agents, such as BRAF, ERBB2, PDGFRB,
      PGR, and KRAS are found in 27.1% of OCCC cases, indicating clinical importance of
      exome analysis for OCCC. Our study suggests that the genetic instability caused
      by either mismatch repair defect or activation of APOBEC play critical roles in
      OCCC carcinogenesis.

PMID- 29044865
TI  - Quick Identification of Piperidine Alkaloid from Roots of Grewia nervosa and
      Their Glucosidase Inhibitory Activity.
AB  - Grewia nervosa is a herbal plant used in traditional medicine for different
      purposes. Bioassay-guided chemical fractionation of G. nervosa roots resulted in
      an identification of two known and one new compound, namely microgrewiapine A,
      homomicrogrewiapine, and N-methylmicrocosamine, respectively. Their structures
      were determined using combination of LC/HR-MS, 1 H-NMR, and IR spectral analyses
      and followed by comparison with those reported in the literature. The problematic
      separation of these alkaloids on traditional column chromatography (Silica gel,
      Octadecyl silane, Sephadex) was resolved by using HPLC. Structurally similar
      compounds from the piperidine family have been characterized by using HR-MS
      analysis in combination with NMR data of crude samples. The major constituent
      i.e. N-methylmicrocosamine isolated from the butanol fraction of methanol root
      extract (MRE) was found to possess the dose dependent alpha-glucosidase
      inhibition activity with an IC50 value of 53.40 MUm. Furthermore, N
      methylmicrocosamine showed maximum alpha-glucosidase inhibition of 97.48 +/- 0.7%
      at 107.5 MUm, which is approximately 1.3 * 103 fold higher than the activity
      shown by acarbose (97.72% inhibition at 61.95 mm), a standard anti-diabetic drug
      available commercially. This work also reports the in vitro alpha-glucosidase
      inhibitory activity of the major alkaloids isolated from G. nervosa for the first
      time.

PMID- 29044866
TI  - High Susceptibility of Histidine to Charge Solvation Revealed by Cold Ion
      Spectroscopy.
AB  - Histidine remained the last aromatic amino acid for which the intrinsic
      spectroscopic properties and structures were obscure. We measured the UV and IR
      spectra of protonated histidine, isolated in the gas phase, using
      photofragmentation cold ion spectroscopy. Unexpectedly, the UV absorption appears
      strongly redshifted relative to that of the cation in aqueous solutions. In
      investigating this phenomenon, we solved the geometries of all abundant
      conformers using IR conformer-selective spectroscopy and ab initio quantum
      chemical calculations. In all of the structures, the proton resides on the
      imidazole ring. The measured UV spectra of protonated methylimidazole, histamine
      and histidine, together with calculations of the electronic spectra for the
      latter, suggest that, in comparison with other aromatic amino acids, such
      location of proton makes UV absorption of histidine highly sensitive to the local
      environment of its side chain.

PMID- 29044867
TI  - Effect of one-time brief additional counseling on periodic health examination for
      40- and 66-year-olds: 2-Year follow up of 101 260 participants.
AB  - AIM: The aim of the present study was to evaluate whether the effect of one-time
      brief additional counseling in periodic health examinations (PHE) through the
      National Screening Program for the Translational Ages in Korea is sustained after
      2 years. METHODS: We collected data from National Screening Program for the
      Translational Ages participants in 2007 and 2008. To evaluate behavior change
      after 2 years, we collected the participants' health behavior data 2 years later
      (2009 and 2010). We defined the basic group as participants who only received
      PHE, and the additional group as received PHE and counseling. We carried out
      propensity score matching to ensure that additional counseling was the only
      different variable affecting health behavior between the two groups. RESULTS:
      After propensity score matching, 50 630 remaining matched participants were
      matched for each group. Of these participants, 26.5% (26 855/101 260) were aged
      66 years, and 60.9% (61 653/101 260) were men. The additional group showed a
      significant increase in odds of smoking cessation among the 66-year-olds
      (adjusted OR 1.173, 95% CI 1.003-1.372). This effect was significant, especially
      when the participants did not have hypertension or hypercholesterolemia (adjusted
      OR 1.193, 95% CI 1.000-1.423 for hypertension and adjusted OR 1.188, 95% CI 1.009
      1.398 for hypercholesterolemia). However, there was no significant association
      for alcohol drinking and regular exercise. CONCLUSIONS: The effect of one-time
      brief counseling added to a PHE in cigarette smoking was observed only among the
      66-year-olds. However, the effect was so small that it is doubtful to be
      clinically relevant. Repeated counseling is required to sustain the effect of the
      initial motivation of counseling. Geriatr Gerontol Int 2018; 18: 329-337.

PMID- 29044868
TI  - Effects of Rubiadin isolated from Prismatomeris connata on anti-hepatitis B virus
      activity in vitro.
AB  - Prismatomeris connata was a kind of Rubiaceae plant for treatment of hepatitis,
      hepatic fibrosis and silicosis. Whereas, the effective components of
      Prismatomeris connata remains unexplored. The aim of this study was to
      investigate the inhibitory effects and mechanisms of Rubiadin isolated from
      Prismatomeris connata against HBV using HepG2.2.15 cells. The levels of hepatitis
      B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core
      antigen (HBcAg) in the supernatants or cytoplasm were examined using by enzyme
      linked immunosorbent assay. HBV DNA was qualified q-PCR. Rubiadin was isolated by
      silica gel column. The structure of the compound was elucidated by HPLC, FT-IR, 1
      H-NMR, 13 C-NMR and identified as 1,3-Dihydroxy-2-methyl-9, 10-anthraquinone.
      Rubiadin significantly decreased HBeAg,HBcAg secretion level and inhibit HBV DNA
      replication. Rubiadin inhibits the proliferation of the cells and HBx protein
      expression in a dose-dependent manner. The intracellular calcium concentration
      was significantly reduced. These results demonstrated that Rubiadin could inhibit
      HepG2.2.15 cells proliferation, reduce the level of HBx expression, and
      intracellular free calcium, which might become a novel anti-HBV drug candidate.

PMID- 29044869
TI  - Polyproline as a Minimal Antifreeze Protein Mimic That Enhances the
      Cryopreservation of Cell Monolayers.
AB  - Tissue engineering, gene therapy, drug screening, and emerging regenerative
      medicine therapies are fundamentally reliant on high-quality adherent cell
      culture, but current methods to cryopreserve cells in this format can give low
      cell yields and require large volumes of solvent "antifreezes". Herein, we report
      polyproline as a minimum (bio)synthetic mimic of antifreeze proteins that is
      accessible by solution, solid-phase, and recombinant methods. We demonstrate that
      polyproline has ice recrystallisation inhibition activity linked to its
      amphipathic helix and that it enhances the DMSO cryopreservation of adherent cell
      lines. Polyproline may be a versatile additive in the emerging field of
      macromolecular cryoprotectants.

PMID- 29044870
TI  - A long way for microRNAs to become meaningful prognostic biomarkers.

PMID- 29044871
TI  - The BRONCH-AHF study: effects on short-term outcome of nebulized bronchodilators
      in emergency department patients diagnosed with acute heart failure.

PMID- 29044872
TI  - Transcranial magnetic stimulation of right inferior parietal cortex causally
      influences prefrontal activation for visual detection.
AB  - For effective interactions with the environment, the brain needs to form
      perceptual decisions based on noisy sensory evidence. Accumulating evidence
      suggests that perceptual decisions are formed by widespread interactions amongst
      sensory areas representing the noisy sensory evidence and fronto-parietal areas
      integrating the evidence into a decision variable that is compared to a
      decisional threshold. This concurrent transcranial magnetic stimulation (TMS)
      fMRI study applied 10 Hz bursts of four TMS (or Sham) pulses to the intraparietal
      sulcus (IPS) to investigate the causal influence of IPS on the neural systems
      involved in perceptual decision-making. Participants had to detect visual signals
      at threshold intensity that were presented in their left lower visual field on
      50% of the trials. Critically, we adjusted the signal strength such that
      participants failed to detect the visual stimulus on approximately 30% of the
      trials allowing us to categorise trials into hits, misses and correct rejections
      (CR). Our results show that IPS-relative to Sham-TMS attenuated activation
      increases for misses relative to CR in the left middle and superior frontal gyri.
      Critically, while IPS-TMS did not significantly affect participants' performance
      accuracy, it affected how observers adjusted their response times after making an
      error. We therefore suggest that activation increases in superior frontal gyri
      for misses relative to correct responses may not be critical for signal detection
      performance, but rather reflect post-decisional processing such as metacognitive
      monitoring of choice accuracy or decisional confidence.

PMID- 29044873
TI  - Unbiased random mutagenesis contributes to a better understanding of the virulent
      behaviour of Paenibacillus larvae.
AB  - AIMS: American foulbrood, caused by the Gram-positive bacteria Paenibacillus
      larvae, is one of the most severe bacterial diseases of the European honey bee.
      The bacterium has been known for long, but only the last decade the mechanisms
      used by the pathogen to cause disease in its host are starting to unravel. In
      this study, the knowledge of this virulent behaviour is expanded and several
      possible virulence factors are suggested. METHODS AND RESULTS: Identification of
      possible virulence factors has been done by random mutagenesis to ensure an
      unbiased approach. A library of mutants was tested for a significant difference
      in virulence using in vitro exposure assays. Affected loci were characterized and
      their potential to contribute in virulence of the pathogen was assessed.
      CONCLUSIONS: The identified mutated loci dacB, dnaK, metN, ywqD, lysC, serC and
      gbpA are known to encode for virulence factors in other bacteria and are
      suggested to play a similar role in P. larvae. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study identified new possible virulence factors for P. larvae genotype
      ERIC I in an unbiased way. This contributes to the knowledge and understanding of
      the possible mechanisms used by this pathogen to colonize and kill its host.

PMID- 29044875
TI  - Consecutive cases of thyrolipomatosis and thymolipoma: a case report.

PMID- 29044874
TI  - Information processing from the motor cortices to the subthalamic nucleus and
      globus pallidus and their somatotopic organizations revealed
      electrophysiologically in monkeys.
AB  - To understand how the information derived from different motor cortical areas
      representing different body parts is organized in the basal ganglia, we examined
      the neuronal responses in the subthalamic nucleus (STN), and the external (GPe)
      and internal (GPi) segments of the globus pallidus (input, relay and output
      nuclei, respectively) to stimulation of the orofacial, forelimb and hindlimb
      regions of the primary motor cortex (MI) and supplementary motor area (SMA) in
      macaque monkeys under the awake state. Most STN and GPe/GPi neurons responded
      exclusively to stimulation of either the MI or SMA, and one-fourth to one-third
      of neurons responded to both. STN neurons responding to the hindlimb, forelimb
      and orofacial regions of the MI were located along the medial-lateral axis in the
      posterolateral STN, while neurons responding to the orofacial region of the SMA
      were located more medially than the others in the anteromedial STN. GPe/GPi
      neurons responding to the hindlimb, forelimb and orofacial regions of the MI were
      found along the dorsal-ventral axis in the posterolateral GPe/GPi, and neurons
      responding to the corresponding regions of the SMA were similarly but less
      clearly distributed in more anteromedial regions. Moreover, neurons responding to
      the distal and proximal forelimb MI regions were found along the lateral-medial
      axis in the STN and the ventral-dorsal axis in the GPe/GPi. Most STN and GPe/GPi
      neurons showed kinaesthetic responses with similar somatotopic maps. These
      observations suggest that the somatotopically organized inputs from the MI and
      SMA are well preserved in the STN and GPe/GPi with partial convergence.

PMID- 29044876
TI  - Chelidonine inhibits TNF-alpha-induced inflammation by suppressing the NF-kappaB
      pathways in HCT116 cells.
AB  - Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) is a
      complex that regulates several hundreds of genes, including those involved in
      immunity and inflammation, survival, proliferation, and the negative feedback of
      NF-kappaB signaling. Chelidonine, a major bioactive, isoquinoline alkaloid
      ingredient in Chelidonium majus, exhibits antiinflammatory pharmacological
      properties. However, its antiinflammatory molecular mechanisms remain unclear. In
      this work, we explored the effect of chelidonine on TNF-induced NF-kappaB
      activation in HCT116 cells. We found chelidonine inhibited the phosphorylation
      and degradation of the inhibitor of NF-kappaB alpha and nuclear translocation of
      RELA. Furthermore, by inhibiting the activation of NF-kappaB, chelidonine
      downregulated target genes involved in inflammation, proliferation, and
      apoptosis. Chelidonine also inhibited mitogen-activated protein kinase pathway
      activation by blocking c-Jun N-terminal kinase and p38 phosphorylation. These
      results suggest that chelidonine may be a potential therapeutic agent against
      inflammatory diseases in which inhibition of NF-kappaB activity plays an
      important role.

PMID- 29044877
TI  - Sustained FXN expression in dorsal root ganglia from a nonreplicative genomic HSV
      1 vector.
AB  - BACKGROUND: Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative
      disease caused by mutations in the frataxin gene (FXN), which lead to reduced
      levels of the essential mitochondrial protein frataxin. Currently, there is no
      effective cure. METHODS: With the aim of developing a gene therapy for FA
      neuropathology, we describe the construction and preliminary characterization of
      a high-capacity nonreplicative genomic herpes simplex virus type 1 vector (H24B
      FXNlac vector) carrying a reduced version of the human FXN genomic locus,
      comprising the 5-kb promoter and the FXN cDNA with the inclusion of intron 1.
      RESULTS: We show that the transgene cassette contains the elements necessary to
      preserve physiological neuronal regulation of human FXN expression. Transduction
      of cultured fetal rat dorsal root ganglia neurons with the H24B-FXNlac vector
      results in sustained expression of human FXN transcripts and frataxin protein.
      Rat footpad inoculation with the H24B-FXNlac vector results in human FXN
      transgene delivery to the dorsal root ganglia, with expression persisting for at
      least 1 month. CONCLUSIONS: The results of the present study support the
      feasibility of using this vector for sustained neuronal expression of human
      frataxin for FA gene therapy.

PMID- 29044878
TI  - The impact of coaches providing healthy snacks at junior sport training.
AB  - OBJECTIVE: Sports clubs provide an opportunity to tackle childhood obesity rates
      through targeted interventions. Our study aimed to investigate if coaches
      providing healthy snacks to participants before junior netball sessions at five
      clubs in Melbourne, Australia, increased consumption of healthy foods and
      influenced coach perceptions of participants' attention/participation levels.
      METHODS: Coaches provided healthy snacks to participants before each netball
      session for one school term. Children's food consumption was observed at one
      session before, during and after the intervention. Parents attending the observed
      session completed pre- and post-intervention questionnaires. Coaches rated
      participants' attention/participation at the observed sessions before and during
      the intervention, and completed a questionnaire post-intervention. RESULTS:
      Baseline: Ice cream and cake were the most frequently consumed snacks. During
      intervention: Fruit, cheese and crackers and vegetables were the most frequently
      consumed snacks. Coaches ratings of participants' attention/participation
      increased significantly (baseline: 6.4 +/- 0.17, intervention: 7.5 +/- 0.36;
      p=0.02) where the same coach undertook ratings at both time points. CONCLUSIONS:
      Coaches providing healthy snacks before sessions at sports clubs increased
      consumption of nutrient-dense foods at the session, and may have positively
      affected participants' attention/participation. Implications for public health:
      This study highlights how a simple intervention could improve the diet of
      Australian children.

PMID- 29044879
TI  - Exercise therapy for trismus secondary to head and neck cancer: A systematic
      review.
AB  - BACKGROUND: Effects of exercise therapy for trismus secondary to head and neck
      cancer have not been reviewed systematically since 2004. METHODS: Four databases
      were searched. The quality of observational studies and randomized controlled
      trials was assessed. RESULTS: Two hundred eleven articles were found, 20 studies
      were included. A large variation in research methodology, stretching techniques,
      duration of stretch, and repetition of exercises was found. The overall quality
      was moderate. Five of the 8 preventive studies found that exercises during
      (chemo)radiotherapy could not prevent a reduction in mouth opening. In 4
      therapeutic case studies, mouth opening increased between 17 and 24 mm. In 8
      other therapeutic studies, mouth opening increased between -1.9 and 13.6 mm. No
      exercise therapy was clearly superior to the others. CONCLUSION: Changes in mouth
      opening ranged considerably and no stretching technique was superior to others
      regarding either prevention or treatment of trismus. Clinical guidelines cannot
      be given based on this systematic review. (c) 2016 Wiley Periodicals, Inc. Head
      Neck 39: 160-169, 2017.

PMID- 29044880
TI  - Targeted deep sequencing of effusion cytology samples is feasible, informs
      spatiotemporal tumor evolution, and has clinical and diagnostic utility.
AB  - During the course of disease, many cancer patients eventually present with
      metastatic disease including peritoneal or pleural spread. In this context,
      cytology specimens derived from ascites or pleural effusion may help to
      differentiate malignant from benign conditions and sometimes yield diagnosis of a
      malignancy. However, even when supported by immunohistochemistry, cytological
      interpretation can be challenging, especially if tumor cellularity is low. Here,
      we investigated whether targeted deep sequencing of formalin-fixed and paraffin
      embedded (FFPE) cytology specimens of cancer patients is feasible, and has
      diagnostic and clinical impact. To this end, a cohort of 20 matched pairs was
      compiled, each comprising a cytology sample (FFPE cell block) and at least one
      biopsy/surgical resection specimen serving as benchmark. In addition, 5 non
      malignant effusions were sequenced serving as negative-controls. All samples
      yielded sufficient libraries and were successfully subjected to targeted
      sequencing employing a semiconductor based next-generation sequencing platform.
      Using gene panels of different size and composition, including the Oncomine
      Comprehensive Assay, for targeted sequencing, somatic mutations were detected in
      the tissue of all 20 cases. Of these, 15 (75%) harbored mutations that were also
      detected in the corresponding cytology samples. In four of these cases (20%),
      additional private mutations were detected in either cytology or tissue samples,
      reflecting spatiotemporal tumor evolution. Of the five remaining cases, three
      (15%) showed wild type alleles in cytology material whereas tumor tissue had
      mutations in interrogated genes. Two cases were discordant, showing different
      private mutations in the cytology and in the tissue sample, respectively. In
      summary, sequencing of cytology specimens (FFPE cell block) reflecting
      spatiotemporal tumor evolution is feasible and yields adjunct genetic information
      that may be exploitable for diagnostics and therapy.

PMID- 29044881
TI  - Local control in sinonasal malignant melanoma: Comparing conventional to
      hypofractionated radiotherapy.
AB  - BACKGROUND: The purpose of this study was to analyze the effect of fractionation
      schedule on local control in postoperative radiotherapy (RT) for sinonasal
      malignant melanoma. METHODS: Sixty-three patients who were treated with surgery
      and postoperative RT in 4 accredited head and neck cancer centers in the
      Netherlands between 1998 and 2013 were retrospectively studied. Outcomes with
      conventional fractionation (2-2.4 Gy per fraction; n = 27) were compared to
      hypofractionation (4-6 Gy per fraction; n = 36). The primary endpoint was local
      control and the secondary endpoint was toxicity. RESULTS: Comparable local
      control rates were found after 2 and 5 years (63% vs 64% and 47% vs 53%; P = .73
      for, respectively, conventional fractionation vs hypofractionation). Local
      recurrences were predominantly present ipsilateral (92%) and within the
      irradiated volume (88%). Late toxicity grade >= 3 was observed in 2 of 63
      patients, 1 patient in both groups. CONCLUSION: Radiotherapy fractionation
      schedule did not influence the local control rate or the incidence of late
      toxicity in patients treated with surgery and RT for sinonasal malignant melanoma
      in this retrospective analysis. Due to this retrospective nature and the limited
      number of patients, strong recommendations cannot be made. Expected toxicity,
      patient convenience, and workload may be taken into account for the choice of
      fractionation schedule until conclusive evidence becomes available.

PMID- 29044883
TI  - Clinical benefit and residual kidney function of en bloc nephrectomy for
      perirenal retroperitoneal sarcoma.
AB  - AIM: The purpose of this study was to evaluate the efficacy of en bloc
      nephrectomy for perirenal retroperitoneal sarcoma (RPS) with respect to
      postoperative kidney function and oncological benefits. METHODS: We performed a
      comparative study of 114 patients undergoing surgery for primary RPS, classifying
      cases as nephrectomy (NPX, n = 65) versus no nephrectomy (no-NPX, n = 49). The
      Delta and % change between preoperative and postoperative estimated glomerulus
      filtration rate (eGFR) were analyzed to compare renal function changes after
      surgery. Kaplan-Meier analysis was performed to verify the incidence of local
      relapse between the two groups. RESULTS: During a median follow-up of 29 months,
      median postoperative GFR of 65 patients in the NPX group decreased to 73.5% of
      preoperative eGFR. Although 38 patients (58%) in the NPX group experienced a
      progression in chronic kidney disease stage after nephrectomy, no patients
      progressed to end-stage renal disease (ESRD). In French Federation of Cancer
      Centers Sarcoma grade 2, the NPX group had statistically significant local
      control benefits, compared with the no-NPX group (P = 0.048). CONCLUSIONS:
      Residual renal function after en bloc nephrectomy was stabilized without
      progression to ESRD. Moreover, en bloc nephrectomy for perirenal RPS might secure
      a complete resection margin for local tumor control.

PMID- 29044882
TI  - Sox2 Communicates with Tregs Through CCL1 to Promote the Stemness Property of
      Breast Cancer Cells.
AB  - As an important component of the tumor microenvironment, CD4+ CD25+ Tregs reduce
      antitumor immunity, promote angiogenesis and metastasis in breast cancer.
      However, their function in regulating the "stemness" of tumor cells and the
      communication between Tregs and cancer stem cells (CSCs) remain elusive. Here, we
      disclose that the primarily cultured Tregs isolated from breast-tumor-bearing
      Foxp3-EGFP mouse upregulate the stemness property of breast cancer cells. Tregs
      increased the side-population and the Aldehyde dehydrogenase-bright population of
      mouse breast cancer cells, promoted their sphere formation in a paracrine manner,
      and enhanced the expression of stemness genes, such as Sox2 and so forth. In
      addition, Tregs increased tumorigenesis, metastasis, and chemoresistance of
      breast cancer cells. Furthermore, Sox2-overexpression tumor cells activated NF
      kappaB-CCL1 signaling to recruit Tregs through reducing the binding of H3K27Me3
      on promoter regions of p65 and Ccl1. These findings reveal the functional
      interaction between Tregs and CSCs and indicate that targeting on the
      communication between them is a promising strategy in breast cancer therapy. Stem
      Cells 2017;35:2351-2365.

PMID- 29044884
TI  - A dexamethasone, melphalan, actinomycin-D and cytarabine chemotherapy protocol as
      a rescue treatment for feline lymphoma.
AB  - Nineteen cats with relapsed high-grade/large-cell lymphoma were treated with
      dexamethasone, melphalan, actinomycin-D and cytarabine (DMAC). All cats had
      received Cyclophosphamide, Vincristine, Prednisolone (COP) as first-line
      chemotherapy and most cats had received at least 2 prior rescue agents with 14 of
      19 having received both epirubicin and lomustine. Five cats (26%) exhibited a
      response (defined as an improvement or resolution of tumour-associated clinical
      signs/tumour volume, or complete/partial response) to chemotherapy though no
      patients received more than 2 cycles of DMAC. Most cats tolerated the protocol
      well though 3 patients exhibited Veterinary Cooperative Oncology Group (VCOG)
      grade 4 neutropenia and 1 patient exhibited grade 4 thrombocytopenia. The median
      progression-free survival and overall survival from starting DMAC were 14 and 17
      days respectively. There is still an unmet need for successful rescue
      chemotherapy protocol for cats with relapsed lymphoma. [Correction added on 02
      November 2017, after first online publication: The expansion for the term DMAC
      was previously incorrect and has been corrected in this current version.].

PMID- 29044885
TI  - Heritability and social brood effects on personality in juvenile and adult life
      history stages in a wild passerine.
AB  - How has evolution led to the variation in behavioural phenotypes (personalities)
      in a population? Knowledge of whether personality is heritable, and to what
      degree it is influenced by the social environment, is crucial to understanding
      its evolutionary significance, yet few estimates are available from natural
      populations. We tracked three behavioural traits during different life-history
      stages in a pedigreed population of wild house sparrows. Using a quantitative
      genetic approach, we demonstrated heritability in adult exploration, and in
      nestling activity after accounting for fixed effects, but not in adult boldness.
      We did not detect maternal effects on any traits, but we did detect a social
      brood effect on nestling activity. Boldness, exploration and nestling activity in
      this population did not form a behavioural syndrome, suggesting that selection
      could act independently on these behavioural traits in this species, although we
      found no consistent support for phenotypic selection on these traits. Our work
      shows that repeatable behaviours can vary in their heritability and that social
      context influences personality traits. Future efforts could separate whether
      personality traits differ in heritability because they have served specific
      functional roles in the evolution of the phenotype or because our concept of
      personality and the stability of behaviour needs to be revised.

PMID- 29044886
TI  - Reducing geriatric outpatient waiting times: Impact of an advanced health
      practitioner.
AB  - OBJECTIVE: To investigate the impact on patient waiting times of a role
      substitution model introducing an advanced allied health practitioner as the
      first point of contact within a geriatric outpatient context. METHODS: A pre- to
      postintervention design was used to determine impact over a five-year period
      (2008-2012). All patients referred to the geriatric specialist outpatient
      department were included (n = 1514). Data relating to waiting times were analysed
      using one-way ANOVA and post hoc Tukey tests to determine effects on patient
      waiting times. RESULTS: Waiting times were reduced from an average of 82 to as
      low as 35 days, in a context of increasing referral rates. Medical specialist
      capacity was increased through improvements to available outpatient times and
      reduced appointment lengths. Patients seen within their designated triage
      category timeframe increased from 47 to 86%. CONCLUSION: Health professional
      substitution in geriatrics can be an effective intervention for reducing patient
      waiting times and improving access to care.

PMID- 29044887
TI  - Quantitative mapping of genetic similarity in human heritable diseases by shared
      mutations.
AB  - Many genetic diseases exhibit considerable epidemiological comorbidity and common
      symptoms, which provokes debate about the extent of their etiological overlap.
      The rapid growth in the number of known disease-causing mutations in the Human
      Gene Mutation Database (HGMD) has allowed us to characterize genetic similarities
      between diseases by ascertaining the extent to which identical genetic mutations
      are shared between diseases. Using this approach, we show that 41.6% of disease
      pairs in all possible pairs (42, 083) exhibit a significant sharing of mutations
      (P value < 0.05). These mutation-related disease pairs are in agreement with
      heritability-based disease-disease relations in 48 neurological and psychiatric
      disease pairs (Spearman's correlation coefficient = 0.50; P value = 3.4 * 10-5 ),
      and share over-expressed genes significantly more often than unrelated disease
      pairs (1.5-1.8-fold higher; P value <= 1.6 * 10-4 ). The usefulness of mutation
      related disease pairs was further demonstrated for predicting novel mutations and
      identifying individuals susceptible to Crohn disease. Moreover, the mutation
      based disease network concurs closely with that based on phenotypes.

PMID- 29044888
TI  - Nuclear magnetic relaxation dispersion of murine tissue for development of T1 (R1
      ) dispersion contrast imaging.
AB  - This study quantified the spin-lattice relaxation rate (R1 ) dispersion of murine
      tissues from 0.24 mT to 3 T. A combination of ex vivo and in vivo spin-lattice
      relaxation rate measurements were acquired for murine tissue. Selected brain,
      liver, kidney, muscle, and fat tissues were excised and R1 dispersion profiles
      were acquired from 0.24 mT to 1.0 T at 37  degrees C, using a fast field-cycling
      MR (FFC-MR) relaxometer. In vivo R1 dispersion profiles of mice were acquired
      from 1.26 T to 1.74 T at 37  degrees C, using FFC-MRI on a 1.5 T scanner
      outfitted with a field-cycling insert electromagnet to dynamically control B0
      prior to imaging. Images at five field strengths (1.26, 1.39, 1.5, 1.61, 1.74 T)
      were acquired using a field-cycling pulse sequence, where B0 was modulated for
      varying relaxation durations prior to imaging. R1 maps and R1 dispersion (DeltaR1
      /DeltaB0 ) were calculated at 1.5 T on a pixel-by-pixel basis. In addition, in
      vivo R1 maps of mice were acquired at 3 T. At fields less than 1 T, a large R1
      magnetic field dependence was observed for tissues. ROI analysis of the tissues
      showed little relaxation dispersion for magnetic fields from 1.26 T to 3 T. Our
      tissue measurements show strong R1 dispersion at field strengths less than 1 T
      and limited R1 dispersion at field strengths greater than 1 T. These findings
      emphasize the inherent weak R1 magnetic field dependence of healthy tissues at
      clinical field strengths. This characteristic of tissues can be exploited by a
      combination of FFC-MRI and T1 contrast agents that exhibit strong relaxivity
      magnetic field dependences (inherent or by binding to a protein), thereby
      increasing the agents' specificity and sensitivity. This development can provide
      potential insights into protein-based biomarkers using FFC-MRI to assess early
      changes in tumour development, which are not easily measureable with conventional
      MRI.

PMID- 29044889
TI  - Side-Group-Mediated Mechanical Conductance Switching in Molecular Junctions.
AB  - A key target in molecular electronics has been molecules having switchable
      electrical properties. Switching between two electrical states has been
      demonstrated using such stimuli as light, electrochemical voltage, complexation
      and mechanical modulation. A classic example of the latter is the switching of
      4,4'-bipyridine, leading to conductance modulation of around 1 order of
      magnitude. Here, we describe the use of side-group chemistry to control the
      properties of a single-molecule electromechanical switch, which can be cycled
      between two conductance states by repeated compression and elongation. While
      bulky alkyl substituents inhibit the switching behavior, pi-conjugated side
      groups reinstate it. DFT calculations show that weak interactions between aryl
      moieties and the metallic electrodes are responsible for the observed phenomenon.
      This represents a significant expansion of the single-molecule electronics "tool
      box" for the design of junctions with electromechanical properties.

PMID- 29044891
TI  - Oxidation of Organic Molecules with a Redox-Active Guanidine Catalyst.
AB  - Herein, we report the first examples of the use of redox-active guanidines as
      catalysts in the green oxidation of organic molecules with dioxygen. In one half
      reaction, the oxidized form of the redox-active guanidine is converted into the
      reduced, protonated state, thereby enabling dehydrogenative oxidation of the
      substrate (3,5-di-tert-butylcatechol->ortho-benzoquinone, benzoin->benzil, and
      2,4-di-tert-butylphenol->biphenol). In the other half-reaction, efficient re
      oxidation of the guanidine to the oxidized state is achieved with dioxygen in the
      presence of a copper catalyst. These results pave the way for the broader use of
      redox-active guanidines as oxidation catalysts.

PMID- 29044890
TI  - Overexpression of serine acetyltransferase in maize leaves increases seed
      specific methionine-rich zeins.
AB  - Maize kernels do not contain enough of the essential sulphur-amino acid
      methionine (Met) to serve as a complete diet for animals, even though maize has
      the genetic capacity to store Met in kernels. Prior studies indicated that the
      availability of the sulphur (S)-amino acids may limit their incorporation into
      seed storage proteins. Serine acetyltransferase (SAT) is a key control point for
      S-assimilation leading to Cys and Met biosynthesis, and SAT overexpression is
      known to enhance S-assimilation without negative impact on plant growth.
      Therefore, we overexpressed Arabidopsis thaliana AtSAT1 in maize under control of
      the leaf bundle sheath cell-specific rbcS1 promoter to determine the impact on
      seed storage protein expression. The transgenic events exhibited up to 12-fold
      higher SAT activity without negative impact on growth. S-assimilation was
      increased in the leaves of SAT overexpressing plants, followed by higher levels
      of storage protein mRNA and storage proteins, particularly the 10-kDa delta-zein,
      during endosperm development. This zein is known to impact the level of Met
      stored in kernels. The elite event with the highest expression of AtSAT1 showed
      1.40-fold increase in kernel Met. When fed to chickens, transgenic AtSAT1 kernels
      significantly increased growth rate compared with the parent maize line. The
      result demonstrates the efficacy of increasing maize nutritional value by SAT
      overexpression without apparent yield loss. Maternal overexpression of SAT in
      vegetative tissues was necessary for high-Met zein accumulation. Moreover, SAT
      overcomes the shortage of S-amino acids that limits the expression and
      accumulation of high-Met zeins during kernel development.

PMID- 29044894
TI  - Immediate Implant Placement and Provisionalization Following Tumor-Resective
      Surgery in the Midfacial Region: A Case Series.
AB  - Surgical and prosthodontic restoration of the midfacial region following tumor
      resection has always posed a considerable challenge, as this area serves crucial
      functional and esthetic roles. Being diagnosed and subsequently treated for
      facial tumors can have an immense psychosocial impact on a patient, as the
      resulting defects are often disfiguring, and lead to an inability to masticate,
      swallow, and speak clearly. Provision of an immediate facial and dental
      prosthesis at the time of surgery can limit these side effects and help reduce
      mental duress on these patients and their families, as well as aid in the process
      of rehabilitation. Rapid prototyping (RP) and 3D printing, as this paper shows,
      assists presurgical planning of the tumor resection, as well as the manufacture
      of maxillofacial and dental prostheses. Often these defects are extensive, so
      prosthesis retention is aided by zygomatic implants placed at the time of
      surgical resection. When placed at this time, and prior to radiation therapy,
      these craniofacial implants have improved survival rates. Thus, this treatment
      modality can improve postoperative recovery considerably, while at the same time
      allowing for cleaning and monitoring of the resected site for tumor recurrence.

PMID- 29044892
TI  - Mouse Parthenogenetic Embryonic Stem Cells with Biparental-Like Expression of
      Imprinted Genes Generate Cortical-Like Neurons That Integrate into the Injured
      Adult Cerebral Cortex.
AB  - One strategy for stem cell-based therapy of the cerebral cortex involves the
      generation and transplantation of functional, histocompatible cortical-like
      neurons from embryonic stem cells (ESCs). Diploid parthenogenetic Pg-ESCs have
      recently emerged as a promising source of histocompatible ESC derivatives for
      organ regeneration but their utility for cerebral cortex therapy is unknown. A
      major concern with Pg-ESCs is genomic imprinting. In contrast with biparental Bp
      ESCs derived from fertilized oocytes, Pg-ESCs harbor two maternal genomes but no
      sperm-derived genome. Pg-ESCs are therefore expected to have aberrant expression
      levels of maternally expressed (MEGs) and paternally expressed (PEGs) imprinted
      genes. Given the roles of imprinted genes in brain development, tissue
      homeostasis and cancer, their deregulation in Pg-ESCs might be incompatible with
      therapy. Here, we report that, unexpectedly, only one gene out of 7 MEGs and 12
      PEGs was differentially expressed between Pg-ESCs and Bp-ESCs while 13 were
      differentially expressed between androgenetic Ag-ESCs and Bp-ESCs, indicating
      that Pg-ESCs but not Ag-ESCs, have a Bp-like imprinting compatible with therapy.
      In vitro, Pg-ESCs generated cortical-like progenitors and electrophysiologically
      active glutamatergic neurons that maintained the Bp-like expression levels for
      most imprinted genes. In vivo, Pg-ESCs participated to the cortical lineage in
      fetal chimeras. Finally, transplanted Pg-ESC derivatives integrated into the
      injured adult cortex and sent axonal projections in the host brain. In
      conclusion, mouse Pg-ESCs generate functional cortical-like neurons with Bp-like
      imprinting and their derivatives properly integrate into both the embryonic
      cortex and the injured adult cortex. Collectively, our data support the utility
      of Pg-ESCs for cortical therapy. Stem Cells 2018;36:192-205.

PMID- 29044893
TI  - Synthetic Klebsiella pneumoniae-Shewanella oneidensis Consortium Enables Glycerol
      Fed High-Performance Microbial Fuel Cells.
AB  - Microbial fuel cell (MFC) is an eco-friendly bio-electrochemical sys-tem that
      uses microorganism as biocatalyst to convert biomass into electricity. Glycerol,
      as a waste in the biodiesel refinery processes, is an appealing substrate for
      MFC. Nevertheless, glycerol cannot be utilized as carbon source by well-known
      exoelectrogens such as Shewanella oneidensis. Herein, to generate electricity by
      rapidly harnessing glycerol, the authors rationally constructed a Klebsiella
      pneumoniae-Shewanella oneidensis microbial consortium to efficiently harvest
      electricity from glyc-erol, in which K. pneumoniae converted glycerol into
      lactate, fed to S. oneidensis as carbon source and electron donor. To improve
      electricity output, the authors systematically engineered the consortium in terms
      of carbon flux distribution and efficiency of extracellular electron transfer
      (EET). To direct more carbon flux to lactate biosynthesis in K. pneumoniae, the
      authors eliminated the ethanol pathway by knocking out the alcohol dehydrogenase
      gene (adhE), and enhanced lactate biosynthesis by heterologously expressing a
      lactate dehydrogen-ase gene (ldhD) from Lactobacillus bulgaricus and a lactate
      transporter gene (lldP) from Escherichia coli. To facilitate EET between S.
      oneidensis and anode surfaces, a biosynthetic flavins pathway from Bacillus
      subtilis is introduced into S. oneidensis. The author further optimized the
      glycerol concentration, thus S. oneidensis could be continuously fed with lactate
      synthesized from K. pneumoniae at a constant rate. Our glycerol-fed MFC generated
      a maximum power density of 19.9 mW/m2 , significantly higher than that of the
      wild-type consor-tium. This work suggested that engineering microbial consortia
      is an effi-cient strategy to expand the spectrum of usable carbon sources and
      promote electricity power production in MFCs.

PMID- 29044895
TI  - Surveying all public drinking water fountains in a city: outdoor field
      observations and Google Street View.
AB  - OBJECTIVE: Drinking fountains are a public amenity that may help counter the
      obesogenic environment (sugary beverages) and reduce the risk of heat stroke
      during heat waves. As a case study, we aimed to survey all public fountains in a
      city: Wellington, New Zealand, and to determine the utility of Google Street View
      in studying drinking fountains. METHODS: Using a sample of all public drinking
      fountains in a City Council map, a field observer assessed their exact location
      and tap functionality, and photographed them. Google Street View was also used by
      the field observer and an independent observer to attempt fountain detection.
      RESULTS: There were 47 fountains, found in only 6% of children's playgrounds and
      29% of the parks (for a sample of the 10 largest suburbs). While the field
      observations showed that all 74 taps at the fountains delivered water, only 47%
      had taps for easy filling of drinking water bottles, and only 15% had bowls for
      dogs to drink from. Visible discolouration from algae/metal degradation was
      adjacent to 47% of nozzles. Google Street View detection of fountains by the
      field observer was successful for 68% and for 52% by the independent observer.
      CONCLUSIONS: The fountains were of generally high quality, but discolouration
      around the nozzle was common. Implications for public health: Additional
      investment in public fountains may be needed.

PMID- 29044897
TI  - A comparison of dietary estimates from the National Aboriginal and Torres Strait
      Islander Health Survey to food and beverage purchase data.
AB  - OBJECTIVE: We compared self-reported dietary intake from the very remote sample
      of the National Aboriginal and Torres Strait Islander Nutrition and Physical
      Activity Survey (VR-NATSINPAS; n=1,363) to one year of food and beverage
      purchases from 20 very remote Indigenous Australian communities (servicing ~8,500
      individuals). METHODS: Differences in food (% energy from food groups) and
      nutrients were analysed using t-test with unequal variance. RESULTS: Per-capita
      energy estimates were not significantly different between the surveys (899
      MJ/person/day [95% confidence interval -152,1950] p=0.094). Self-reported intakes
      of sugar, cereal products/dishes, beverages, fats/oils, milk products/dishes and
      confectionery were significantly lower than that purchased, while intakes of
      meat, vegetables, cereal-based dishes, fish, fruit and eggs were significantly
      higher (p<0.05). CONCLUSION: Differences between methods are consistent with
      differential reporting bias seen in self-reported dietary data. Implications for
      public health: The NATSINPAS provides valuable, much-needed information about
      dietary intake; however, self-reported data is prone to energy under-reporting
      and reporting bias. Purchase data can be used to track population-level food and
      nutrient availability in this population longitudinally; however, further
      evidence is needed on approaches to estimate wastage and foods sourced outside
      the store. There is potential for these data to complement each other to inform
      nutrition policies and programs in this population.

PMID- 29044896
TI  - Support vector machine for breast cancer classification using diffusion-weighted
      MRI histogram features: Preliminary study.
AB  - BACKGROUND: Diffusion-weighted MRI (DWI) is currently one of the fastest
      developing MRI-based techniques in oncology. Histogram properties from model
      fitting of DWI are useful features for differentiation of lesions, and
      classification can potentially be improved by machine learning. PURPOSE: To
      evaluate classification of malignant and benign tumors and breast cancer subtypes
      using support vector machine (SVM). STUDY TYPE: Prospective. SUBJECTS: Fifty-one
      patients with benign (n = 23) and malignant (n = 28) breast tumors (26 ER+,
      whereof six were HER2+). FIELD STRENGTH/SEQUENCE: Patients were imaged with DW
      MRI (3T) using twice refocused spin-echo echo-planar imaging with echo time /
      repetition time (TR/TE) = 9000/86 msec, 90 * 90 matrix size, 2 * 2 mm in-plane
      resolution, 2.5 mm slice thickness, and 13 b-values. ASSESSMENT: Apparent
      diffusion coefficient (ADC), relative enhanced diffusivity (RED), and the
      intravoxel incoherent motion (IVIM) parameters diffusivity (D), pseudo
      diffusivity (D*), and perfusion fraction (f) were calculated. The histogram
      properties (median, mean, standard deviation, skewness, kurtosis) were used as
      features in SVM (10-fold cross-validation) for differentiation of lesions and
      subtyping. STATISTICAL TESTS: Accuracies of the SVM classifications were
      calculated to find the combination of features with highest prediction accuracy.
      Mann-Whitney tests were performed for univariate comparisons. RESULTS: For benign
      versus malignant tumors, univariate analysis found 11 histogram properties to be
      significant differentiators. Using SVM, the highest accuracy (0.96) was achieved
      from a single feature (mean of RED), or from three feature combinations of IVIM
      or ADC. Combining features from all models gave perfect classification. No single
      feature predicted HER2 status of ER + tumors (univariate or SVM), although high
      accuracy (0.90) was achieved with SVM combining several features. Importantly,
      these features had to include higher-order statistics (kurtosis and skewness),
      indicating the importance to account for heterogeneity. DATA CONCLUSION: Our
      findings suggest that SVM, using features from a combination of diffusion models,
      improves prediction accuracy for differentiation of benign versus malignant
      breast tumors, and may further assist in subtyping of breast cancer. LEVEL OF
      EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1205
      1216.

PMID- 29044898
TI  - Use of computed tomography and minimum intensity projection in the detection of
      lobar pneumonia mimicking lung lobe torsion in a dog.
AB  - A 10-year-old female spayed Dachshund was referred with progressive coughing for
      1 month. The dog was tentatively diagnosed with right middle lung torsion based
      on pleural effusion, vesicular emphysema, abruptly ending bronchus in
      consolidated right middle lung, and no contrast enhancement of the affected lobe
      on radiography and computed tomography (CT). There was no evidence of torsion
      upon thoracotomy, and histological examination confirmed lobar pneumonia. The CT
      images were reevaluated using minimum intensity projection and revealed normal
      bronchial courses. The minimum intensity projection technique can be to assist in
      evaluation of the bronchial tree for dogs with suspected lung lobe torsion and
      other pulmonary diseases.

PMID- 29044899
TI  - A pH-Dependent, Mechanically Interlocked Switch: Organometallic [2]Rotaxane vs.
      Organic [3]Rotaxane.
AB  - We present the first [2]rotaxane featuring a functional organometallic host. In
      contrast to the known organic scaffolds, this assembly shows a high post
      synthetic modifiability. The reactivity of the Ag8 pillarplex host is fully
      retained, as is exemplified by the first transmetalation in a rotaxane framework
      to provide the respective Au8 analogue. Additionally, a transformation under
      acidic conditions to give a purely organic [3]rotaxane is demonstrated which is
      reversible upon addition of a suitable base, rendering the assembly a pH
      dependent switch. Hereby, it is shown that the mechanically interlocked nature of
      the system enhances the kinetic stability of the NHC host complex by a factor of
      >1000 and corresponds to the first observation of a stabilizing "rotaxand
      effect".

PMID- 29044900
TI  - Enantioselective Copper-Catalyzed Alkylation of Quinoline N-Oxides with
      Vinylarenes.
AB  - An asymmetric copper-catalyzed alkylation of quinoline N-oxides with chiral Cu
      alkyl species, generated by migratory insertion of a vinylarene into a chiral Cu
      H complex, is reported. A variety of quinoline N-oxides and vinylarenes underwent
      this Cu-catalyzed enantioselective alkylation reaction, affording the
      corresponding chiral alkylated N-heteroarenes in high yield with high-to
      excellent enantioselectivity. This enantioselective protocol represents the first
      general and practical approach to access a wide range of chiral alkylated
      quinolines.

PMID- 29044901
TI  - Fast, Efficient and Low E-Factor One-Pot Palladium-Catalyzed Cross-Coupling of
      (Hetero)Arenes.
AB  - The homocoupling of aryl halides and the heterocoupling of aryl halides with
      either aryl bromides or arenes bearing an ortho-lithiation directing group are
      presented. The use of a Pd catalyst, in combination with t-BuLi, allows for the
      rapid and efficient formation of a wide range of polyaromatic compounds in a one
      pot procedure bypassing the need for the separate preformation of an
      organometallic coupling partner. These polyaromatic structures are obtained in
      high yields, in 10 min at room temperature, with minimal waste generation (E
      factors as low as 1.5) and without the need for strict inert conditions, making
      this process highly efficient and practical in comparison to classical methods.
      As illustration, several key intermediates of widely used BINOL-derived
      structures are readily prepared.

PMID- 29044902
TI  - Squaramide-Catalyzed Asymmetric aza-Friedel-Crafts/N,O-Acetalization Domino
      Reactions Between 2-Naphthols and Pyrazolinone Ketimines.
AB  - N-Boc ketimines derived from pyrazolin-5-ones were explored to develop an
      unprecedented domino aza-Friedel-Crafts/N,O-acetalization reaction with 2
      naphthols. The novel method requires a catalyst loading of only 0.5 mol % of a
      bifunctional squaramide catalyst, is scalable to gram amounts, and provides a new
      series of furanonaphthopyrazolidinone derivatives bearing two vicinal tetra
      substituted stereogenic centers in excellent yields (95-98 %) and
      stereoselectivity (>99:1 d.r. and 97-98 % ee). A different reactivity was
      observed in the case of 1-naphthols and other electron-rich phenols, which led to
      the aza-Friedel-Crafts adducts in 70-98 % yield and 47-98 % ee.

PMID- 29044903
TI  - Native T1 mapping for characterization of acute and chronic myocardial infarction
      in swine: Comparison with contrast-enhanced MRI.
AB  - BACKGROUND: Both acute and chronic myocardial infarction (AMI and CMI,
      respectively) exhibit delayed enhancement; however, clinical decision-making
      processes frequently require the differentiation of these two types of myocardial
      injury. PURPOSE: To investigate the reliability of AMI and CMI characterization
      using native T1 mapping and its feasibility for discriminating AMI from CMI.
      STUDY TYPE: Case-control. ANIMAL MODEL: The study cohort comprised 12 AMI (mean
      post-MI, 3.75 +/- 1.29 days) and 15 CMI (mean post-MI, 39.53 +/- 6.10 days) Bama
      mini-pigs. FIELD STRENGTH/SEQUENCE: Balanced steady-state free precession
      (bSSFP), segmented-turbo-FLASH-PSIR, and modified Look-Locker inversion recovery
      (MOLLI) sequences at 3.0T. ASSESSMENT: The infarct sizes were compared on
      matching short-axis slices of late-gadolinium-enhanced (LGE) images and T1 maps
      by two experienced radiologists. STATISTICAL TESTS: The infarct sizes were
      compared on matching short-axis slices of LGE images and T1 maps, and agreement
      was determined using linear regression and Bland-Altman analyses. The native T1
      values were compared between AMI and CMI models (independent sample t-test). The
      intraclass correlation coefficient was used to assess inter- and intraobserver
      variability. RESULTS: Measured infarct sizes did not differ between native T1
      mapping and LGE images (AMI: P = 0.913; CMI: P = 0.233), and good agreement was
      observed between the two techniques (AMI: bias, -3.38 +/- 19.38%; R2  = 0.96;
      CMI: bias, -10.55 +/- 10.90%; R2  = 0.90). However, the native infarction
      myocardium T1 values and the T1 signal intensity ratio of infarct and remote
      myocardium (T1 SI ratio) did not differ significantly between AMI and CMI (P =
      0.173). DATA CONCLUSION: Noncontrast native T1 mapping can accurately determine
      acute and chronic infarct areas as well as conventional LGE imaging; however, it
      cannot distinguish acute from chronic MI. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1406-1414.

PMID- 29044904
TI  - Diabetes mellitus and amyotrophic lateral sclerosis: time to bridge the gap
      between the bench and the bedside.

PMID- 29044905
TI  - Efficacy and Safety of Postoperative Pain Relief by Parecoxib Injection after
      Laparoscopic Surgeries: A Systematic Review and Meta-analysis of Randomized
      Controlled Trials.
AB  - OBJECTIVE: This study aims to evaluate the efficacy and safety of parecoxib
      injection in pain relief after laparoscopic surgeries. METHODS: A comprehensive
      literature search based on 4 online databases (PubMed, Embase, Cochrane Central
      Register of Controlled Trials, and Web of Science) was applied to retrieve all
      related randomized controlled trials (RCTs). Two independent reviewers screened
      each article for eligibility according to the predetermined inclusion criteria.
      The Cochrane Collaboration's tool was applied to evaluate the methodological
      quality of included studies. A standardized data collection sheet was designed to
      extract data from included studies. RevMan version 5.3 (The Cochrane
      Collaboration, Copenhagen, Denmark) was selected to perform meta-analysis.
      RESULTS: A total of 1,060 participants who were scheduled for gynecological
      laparoscopic surgery or laparoscopic cholecystectomy (LC) were enrolled in 12
      selected RCTs. The methodological qualities of the studies were evaluated as
      moderate to high. The combined data showed that perioperative parecoxib injection
      could significantly reduce the proportion of patients who required adjuvant pain
      relieve after laparoscopic surgeries. Significantly lower pain scores in the
      parecoxib groups were observed, which proved that preoperative or intraoperative
      injection of 40 mg parecoxib was more effective than placebo for immediate pain
      relief after LC. But preoperative injection of 40 mg parecoxib showed no
      improvement compared with placebo in the management of immediate pain following
      gynecological laparoscopic surgery. The occurrence of adverse events showed no
      differences between perioperative parecoxib administration and placebo control.
      CONCLUSION: Perioperative parecoxib administration was effective in reducing the
      proportion of patients who required adjuvant pain relief after laparoscopic
      surgeries without significant adverse events compared with placebo. The effect of
      parecoxib injection on immediate pain relief remains in question. Future RCTs
      with larger sample sizes are encouraged.

PMID- 29044906
TI  - Long-term follow up of a massive, conservatively treated, splenic infarction in a
      young adolescent.

PMID- 29044907
TI  - Barriers and facilitators for health professionals referring Aboriginal and
      Torres Strait Islander tobacco smokers to the Quitline.
AB  - OBJECTIVE: To examine the barriers and facilitators among health professionals to
      providing referrals to Quitline for Aboriginal and Torres Strait Islander clients
      who smoke. METHODS: A brief online survey, based on the Theoretical Domains
      Framework, was completed by 34 health professionals who work with Aboriginal and
      Torres Strait Islander people in South Australia and the Northern Territory.
      RESULTS: Respondents who frequently made referrals had higher domain scores than
      less frequent referrers for 'Skills and knowledge' (M=4.44 SD=0.39 vs. M=4.09
      SD=0.47, p<0.05) and 'beliefs about capabilities' (M=4.33 SD=0.44 vs. M=3.88
      SD=0.42, p<0.01). Barriers to providing referrals to Quitline were lack of client
      access to a phone, cost of a phone call, preference for face-to-face
      interventions, and low client motivation to quit. CONCLUSIONS: Health
      professionals working with Aboriginal and Torres Strait Islander clients should
      be supported to build their skills and confidence to provide referrals to
      Quitline and other brief cessation interventions. Building capacity for face-to
      face support locally would be beneficial where phone support is not preferable.
      Implications for public health: Engaging with health professionals who work with
      Aboriginal and Torres Strait Islander people to increase referrals to Quitline is
      strategic as it builds on their existing capacity to provide cessation support.

PMID- 29044909
TI  - Recruitment of 7SL RNA to assembling HIV-1 virus-like particles.
AB  - Retroviruses incorporate specific host cell RNAs into virions. In particular, the
      host noncoding 7SL RNA is highly abundant in all examined retroviruses compared
      with its cellular levels or relative to common mRNAs such as actin. Using live
      cell imaging techniques, we have determined that the 7SL RNA does not arrive with
      the HIV-1 RNA genome. Instead, it is recruited contemporaneously with assembly of
      the protein HIV-1 Gag at the plasma membrane. Further, we demonstrate that
      complexes of 7SL RNA and Gag can be immunoprecipitated from both cytosolic and
      plasma membrane fractions. This indicates that 7SL RNAs likely interact with Gag
      prior to high-order Gag multimerization at the plasma membrane. Thus, the
      interactions between Gag and the host RNA 7SL occur independent of the
      interactions between Gag and the host endosomal sorting complex required for
      transport (ESCRT) proteins, which are recruited temporarily at late stages of
      assembly. The interactions of 7SL and Gag are also independent of interactions of
      Gag and the HIV-1 genome which are seen on the plasma membrane prior to assembly
      of Gag.

PMID- 29044908
TI  - Tumor radiomic heterogeneity: Multiparametric functional imaging to characterize
      variability and predict response following cervical cancer radiation therapy.
AB  - BACKGROUND: Robust approaches to quantify tumor heterogeneity are needed to
      provide early decision support for precise individualized therapy. PURPOSE: To
      conduct a technical exploration of longitudinal changes in tumor heterogeneity
      patterns on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI),
      diffusion-weighted imaging (DWI) and FDG positron emission tomography / computed
      tomography (PET/CT), and their association to radiation therapy (RT) response in
      cervical cancer. STUDY TYPE: Prospective observational study with longitudinal
      MRI and PET/CT pre-RT, early-RT (2 weeks), and mid-RT (5 weeks). POPULATION:
      Twenty-one FIGO IB2 -IVA cervical cancer patients receiving definitive external
      beam RT and brachytherapy. FIELD STRENGTH/SEQUENCE: 1.5T, precontrast axial T1 
      weighted, axial and sagittal T2 -weighted, sagittal DWI (multi-b values),
      sagittal DCE MRI (<10 sec temporal resolution), postcontrast axial T1 -weighted.
      ASSESSMENT: Response assessment 1 month after completion of treatment by a board
      certified radiation oncologist from manually delineated tumor volume changes.
      STATISTICAL TESTS: Intensity histogram (IH) quantiles (DCE SI10% and DWI ADC10% ,
      FDG-PET SUVmax ) and distribution moments (mean, variance, skewness, kurtosis)
      were extracted. Differences in IH features between timepoints and modalities were
      evaluated by Skillings-Mack tests with Holm's correction. Area under receiver
      operating characteristic curve (AUC) and Mann-Whitney testing was performed to
      discriminate treatment response using IH features. RESULTS: Tumor IH means and
      quantiles varied significantly during RT (SUVmean : ?28-47%, SUVmax : ?30-59%,
      SImean : ?8-30%, SI10% : ?8-19%, ADCmean : ?16%, P < 0.02 for each). Among IH
      heterogeneity features, FDG-PET SUVCoV (?16-30%, P = 0.011) and DW-MRI
      ADCskewness decreased (P = 0.001). FDG-PET SUVCoV was higher than DCE-MRI SICoV
      and DW-MRI ADCCoV at baseline (P < 0.001) and 2 weeks (P = 0.010). FDG-PET
      SUVkurtosis was lower than DCE-MRI SIkurtosis and DW-MRI ADCkurtosis at baseline
      (P = 0.001). Some IH features appeared to associate with favorable tumor
      response, including large early RT changes in DW-MRI ADCskewness (AUC = 0.86).
      DATA CONCLUSION: Preliminary findings show tumor heterogeneity was variable
      between patients, modalities, and timepoints. Radiomic assessment of changing
      tumor heterogeneity has the potential to personalize treatment and power outcome
      prediction. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson.
      Imaging 2018;47:1388-1396.

PMID- 29044910
TI  - Colorimetric detection of oxalate in aqueous solution by a pyrogallol red-based
      Cu2+ complex.
AB  - The pyrogallol red (PR)-based Cu2+ complex was proven to be an effective and
      selective colorimetric chemosensing ensemble for recognition of oxalate over
      other anions in a perfect aqueous solution. The addition of oxalate to the PR
      Cu2+ complex resulted in a colour change from purple to orange colour due to the
      regeneration of PR by the chelation of oxalate with Cu2+ , while other anions did
      not induce any significant colour change. Moreover, it was revealed that no
      obvious interference was observed during the titrations with oxalate into each
      other anion. Therefore, the PR-Cu2+ complex can be used as a simple and practical
      colorimetric chemosensor for detecting oxalate.

PMID- 29044911
TI  - Split-graft liver transplantation from an adult donor with an unrecognized UCD to
      a pediatric and adult recipient.
AB  - We report the outcomes of an adult and pediatric split liver transplant from an
      adult male donor who died due to an unrecognized UCD, OTC deficiency. Recognizing
      inborn errors of metabolism can be challenging, especially in adult centers where
      such disorders are rarely encountered. Shortage of donors for liver
      transplantation has led to procedures to maximize donor utilization, such as
      split and live donor grafts. The cause of death should be ascertained before
      accepting a cadaveric donor organ.

PMID- 29044912
TI  - Sequential Coalescence Enabled Two-Step Microreactions in Triple-Core Double
      Emulsion Droplets Triggered by an Electric Field.
AB  - Advances in microfluidic emulsification have enabled the generation of exquisite
      multiple-core droplets, which are promising structures to accommodate
      microreactions. An essential requirement for conducting reactions is the
      sequential coalescence of the multiple cores encapsulated within these droplets,
      therefore, mixing the reagents together in a controlled sequence. Here, a
      microfluidic approach is reported for the conduction of two-step microreactions
      by electrically fusing three cores inside double-emulsion droplets. Using a
      microcapillary glass device, monodisperse water-in-oil-in-water droplets are
      fabricated with three compartmented reagents encapsulated inside. An AC electric
      field is then applied through a polydimethylsiloxane chip to trigger the
      sequential mixing of the reagents, where the precise sequence is guaranteed by
      the discrepancy of the volume or conductivity of the inner cores. A two-step
      reaction in each droplet is ensured by two times of core coalescence, which
      totally takes 20-40 s depending on varying conditions. The optimal parameters of
      the AC signal for the sequential fusion of the inner droplets are identified.
      Moreover, the capability of this technique is demonstrated by conducting an
      enzyme-catalyzed reaction used for glucose detection with the double-emulsion
      droplets. This technique should benefit a wide range of applications that require
      multistep reactions in micrometer scale.

PMID- 29044913
TI  - Assessment of cytologic differentiation in high-grade pancreatic neuroendocrine
      neoplasms: A multi-institutional study.
AB  - BACKGROUND: Well-differentiated (WD) and poorly differentiated (PD) pancreatic
      neuroendocrine neoplasms are biologically distinct entities with different
      therapies and prognoses. WD neoplasms with elevated proliferation (Ki-67 > 20%)
      have been shown to have an overlapping histology with PD neuroendocrine
      carcinomas. This study compared expert cytomorphologic assessments of
      differentiation in pancreatic neuroendocrine neoplasms in a multi-institutional
      study. METHODS: Fine-needle aspiration specimens from pancreatic neuroendocrine
      neoplasms (grade 2 [G2] and grade 3 [G3] according to the 2017 World Health
      Organization classification; n = 72) were diagnosed independently by 3
      cytopathologists as WD or PD (poorly differentiated large cell type [PD-L] or
      poorly differentiated small cell type [PD-S]) purely on the basis of
      cytomorphology. Their diagnoses were compared with a final classification
      supported by immunohistochemistry (retinoblastoma (RB), death domain- associated
      protein (DAXX), and alpha thalassemia/mental retardation syndrome X-linked (ATRX)
      protein expression), targeted mutation analysis (Memorial Sloan Kettering
      Integrated Mutation Profiling of Actionable Cancer Targets), prior history of
      G1/G2 histology, and consensus. RESULTS: The rate of agreement on differentiation
      was 38% (15 WD cases and 12 PD cases) for the 70 cases included (55 WD cases [n =
      19 G2, n = 31 G3, and n = 5 could not be graded] and 15 PD cases [n = 6 PD-S, n =
      6 PD-L, and n = 3 PD, not otherwise specified). Two cases could not be classified
      by the employed methods. PD carcinomas had a higher rate of agreement (10 of 15
      [67%]) than WD neoplasms (15 of 55 [27%]). Round nuclei and plasmacytoid cells
      were associated with agreement for WD cases, whereas apoptosis and angulated
      nuclei were associated with disagreement. Necrosis was associated with agreement
      for PD cases. CONCLUSIONS: A purely morphologic approach to the distinction
      between G2 and G3 pancreatic neuroendocrine neoplasms based on cytology can be
      challenging, with disagreement found among experienced cytopathologists. Cancer
      Cytopathol 2018;126:44-53. (c) 2017 American Cancer Society.

PMID- 29044914
TI  - A Facile Cyclization Method Improves Peptide Serum Stability and Confers
      Intrinsic Fluorescence.
AB  - Peptides are a growing class of macromolecules used in pharmaceutics. The path
      toward the clinical use of candidate peptides involves sequence optimization and
      cyclization for stability and affinity. For internalized peptides, tagging is
      also often required for intracellular trafficking studies, although fluorophore
      conjugation has an impact on peptide binding, permeability, and localization.
      Herein, a strategy based on cysteine arylation with tetrafluoroterephthalonitrile
      (4F-2CN), which simultaneously cyclizes peptides and imparts fluorescence, is
      reported. The 4F-2CN cyclization of an M2 macrophage-targeting peptide yields, in
      a single step, a peptide with improved serum stability, intrinsic fluorescence,
      and increased binding affinity. In a murine breast cancer model, it is
      demonstrated that the intrinsic fluorescence from the cyclized peptide is
      sufficient for monitoring biodistribution by whole-organ fluorescence imaging and
      cell internalization by flow cytometry.

PMID- 29044915
TI  - Pre-discharge and early post-discharge troponin elevation among patients
      hospitalized for heart failure with reduced ejection fraction: findings from the
      ASTRONAUT trial.
AB  - AIMS: Troponin levels are commonly elevated among patients hospitalized for heart
      failure (HF), but the prevalence and prognostic significance of early post
      discharge troponin elevation are unclear. This study sought to describe the
      frequency and prognostic value of pre-discharge and post-discharge troponin
      elevation, including persistent troponin elevation from the inpatient to
      outpatient settings. METHODS AND RESULTS: The ASTRONAUT trial (NCT00894387;
      http://www.clinicaltrials.gov) enrolled hospitalized HF patients with ejection
      fraction <=40% and measured troponin I prior to discharge (i.e. study baseline)
      and at 1-month follow-up in a core laboratory (elevation defined as >0.04 ng/mL).
      This analysis included 1469 (91.0%) patients with pre-discharge troponin data.
      Overall, 41.5% and 29.9% of patients had elevated pre-discharge [median: 0.09
      ng/mL; interquartile range (IQR): 0.06-0.19 ng/mL] and 1-month (median: 0.09
      ng/mL; IQR: 0.06-0.15 ng/mL) troponin levels, respectively. Among patients with
      pre-discharge troponin elevation, 60.4% had persistent elevation at 1 month.
      After adjustment, pre-discharge troponin elevation was not associated with 12
      month clinical outcomes. In contrast, 1-month troponin elevation was
      independently predictive of increased all-cause mortality [hazard ratio (HR)
      1.59, 95% confidence interval (CI) 1.18-2.13] and cardiovascular mortality or HF
      hospitalization (HR 1.28, 95% CI 1.03-1.58) at 12 months. Associations between 1
      month troponin elevation and outcomes were similar among patients with newly
      elevated (i.e. normal pre-discharge) and persistently elevated levels
      (interaction P >= 0.16). The prognostic value of 1-month troponin elevation for
      12-month mortality was driven by a pronounced association among patients with
      coronary artery disease (interaction P = 0.009). CONCLUSIONS: In this
      hospitalized HF population, troponin I elevation was common during index
      hospitalization and at 1-month follow-up. Elevated troponin I level at 1 month,
      but not pre-discharge, was independently predictive of increased clinical events
      at 12 months. Early post-discharge troponin I measurement may offer a practical
      means of risk stratification and should be investigated as a therapeutic target.

PMID- 29044917
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 44/2017.

PMID- 29044916
TI  - Free-Standing Polyurethane Nanofiber/Nets Air Filters for Effective PM Capture.
AB  - The filtration performance and light transmittance of nanofiber air filters are
      restricted by their thick fiber diameter, large pore size, and substrate
      dependence, which can be solved by constructing substrate-free fibrous membranes
      with true nanoscale diameters and ultrathin thicknesses, however, it has proven
      to be extremely challenging. Herein, a roust approach is presented to create free
      standing polyurethane (PU) nanofiber/nets air filters composed of bonded
      nanofibers and 2D nanonets for particular matter (PM) capture via combining
      electrospinning/netting technique and facile peel off process from designed
      substrates. This strategy causes widely distributed Steiner-tree structured
      nanonets with diameters of ~20 nm and bonded scaffold nanofibers to assemble into
      ultrathin membranes with small pore size, high porosity, and robust mechanical
      strength on a large scale based on ionic liquid inspiration and surface structure
      optimization of receiver substrates. As a consequence, the resulting free
      standing PU nanofiber/nets filters exhibit high PM1-0.5 removal efficiency of
      >99.00% and PM2.5-1 removal efficiency of >99.73%, maintaining high light
      transmittance of ~70% and low pressure drop of 28 Pa; even achieve >99.97%
      removal efficiency with ~40% transmittance for PM0.3 filtration, and robust
      purification capacity for real smoke PM2.5 , making them promising high
      efficiency and transparent filtration materials for various filtration and
      separation applications.

PMID- 29044918
TI  - Supramolecular Recognition Allows Remote, Site-Selective C-H Oxidation of
      Methylenic Sites in Linear Amines.
AB  - Site-selective C-H functionalization of aliphatic alkyl chains is a longstanding
      challenge in oxidation catalysis, given the comparable relative reactivity of the
      different methylenes. A supramolecular, bioinspired approach is described to
      address this challenge. A Mn complex able to catalyze C(sp3 )-H hydroxylation
      with H2 O2 is equipped with 18-benzocrown-6 ether receptors that bind ammonium
      substrates via hydrogen bonding. Reversible pre-association of protonated primary
      aliphatic amines with the crown ether selectively exposes remote positions (C8
      and C9) to the oxidizing unit, resulting in a site-selective oxidation.
      Remarkably, such control of selectivity retains its efficiency for a whole series
      of linear amines, overriding the intrinsic reactivity of C-H bonds, no matter the
      chain length.

PMID- 29044919
TI  - Exploring the link between high grade internal rectal prolapse and faecal
      incontinence.

PMID- 29044920
TI  - Co-responding police-mental health programmes: Service user experiences and
      outcomes in a large urban centre.
AB  - As police officers are often the first responders to mental health crises, a
      number of approaches have emerged to support skilled police crisis responses. One
      such approach is the police-mental health co-responding team model, whereby
      mental health nurses and police officers jointly respond to mental health crises
      in the community. In the present mixed-method study, we evaluated outcomes of co
      responding team interactions at a large Canadian urban centre by analysing
      administrative data for 2743 such interactions, and where comparison data were
      available, compared them to 16 226 police-only team responses. To understand
      service user experiences, we recruited 15 service users for in-depth qualitative
      interviews, and completed inductive thematic analysis. Co-responding team
      interactions had low rates of injury and arrest, and compared to police-only
      teams, co-responding teams had higher overall rates of escorts to hospital, but
      lower rates of involuntary escorts. Co-responding teams also spent less time on
      hospital handovers than police-only teams. Service users valued responders with
      mental health knowledge and verbal de-escalation skills, as well as a
      compassionate, empowering, and non-criminalizing approach. Current findings
      suggest that co-responding teams could be a useful component of existing crisis
      response systems.

PMID- 29044922
TI  - Nobel Prizes 2017.

PMID- 29044921
TI  - Adult intussusception: a rare but important clinical entity.

PMID- 29044923
TI  - Mitral interventions in heart failure: time to deliver on the promise.

PMID- 29044924
TI  - Molecular Phylogeny and Surface Morphology of Thiriotia hyperdolphinae n. sp. and
      Cephaloidophora oradareae n. sp. (Gregarinasina, Apicomplexa) Isolated from a
      Deep Sea Oradarea sp. (Amphipoda) in the West Pacific.
AB  - In an effort to broaden our understanding of the biodiversity and distribution of
      gregarines infecting crustaceans, this study describes two new species of
      gregarines, Thiriotia hyperdolphinae n. sp. and Cephaloidophora oradareae n. sp.,
      parasitizing a deep sea amphipod (Oradarea sp.). Amphipods were collected using
      the ROV Hyper-Dolphin at a depth of 855 m while on a cruise in Sagami Bay, Japan.
      Gregarine trophozoites and gamonts were isolated from the gut of the amphipod and
      studied with light and scanning electron microscopy, and phylogenetic analysis of
      18S rDNA. Thiriotia hyperdolphinae n. sp. was distinguished from existing species
      based on morphology, phylogenetic position, as well as host niche and geographic
      locality. Cephaloidophora oradareae n. sp. distinguished itself from existing
      Cephaloidophora, based on a difference in host (Oradarea sp.), geographic
      location, and to a certain extent morphology. We established this latter new
      species with the understanding that a more comprehensive examination of diversity
      at the molecular level is necessary within Cephaloidophora. Results from the 18S
      rDNA molecular phylogeny showed that T. hyperdolphinae n. sp. was positioned
      within a clade consisting of Thiriotia spp., while C. oradareae n. sp. grouped
      within the Cephaloidophoridae. Still, supplemental genetic information from
      gregarines infecting crustaceans will be needed to better understand
      relationships within this group of apicomplexans.

PMID- 29044925
TI  - Edith Flanigen Award: J. Zecevic / Hamburger Wissenschaftspreis: X. Feng and K.
      Mullen / Bohlmann Lectureship: A. Furstner.

PMID- 29044927
TI  - Knockout of histamine receptor H3 alters adaptation to sudden darkness and
      monoamine levels in the zebrafish.
AB  - AIM: Histamine receptor H3 (HRH3) has substantial neuropharmacological potential.
      Currently, knockout models of this receptor have been investigated only in mice.
      We characterized the expression of this receptor in the zebrafish and generated a
      zebrafish HRH3 knockout line. Using this model, we studied the role of HRH3 in
      important behaviours. We also analysed the effect of HRH3 knockout on
      monoaminergic systems, which has not been thoroughly studied in any animal model.
      METHODS: Generation of a mutant zebrafish line using the CRISPR-Cas9 system.
      Analysis of locomotor and social behaviour. Expression of HRH3 was characterized
      using in situ hybridization. Analysis of monoamine networks using HPLC,
      immunohistochemistry and quantitative PCR. RESULTS: We found that HRH3 knockout
      zebrafish larvae showed a shorter period of increased locomotion after a sudden
      onset of darkness, while the knockout larvae had a wild-type-like acute response
      to sudden darkness. Adult knockout fish showed decreased swimming velocity,
      although locomotor activity of knockout larvae was unaltered. Additionally,
      levels of dopamine and serotonin were significantly decreased in the knockout
      fish, while monoamine-related gene expression and immunohistochemistry patterns
      were unchanged. CONCLUSIONS: Our results show that HRH3 knockout larvae adapt
      faster to sudden darkness, suggesting a role for this receptor in regulating
      responses to changes in the environment. The decreased levels of dopamine and
      serotonin provide the first direct evidence that knockout of HRH3 alters these
      systems.

PMID- 29044926
TI  - Optical coherence tomography guided carotid artery stent procedure: technique and
      potential applications.
AB  - OBJECTIVES: To (1) present a guide on how to perform optical coherence tomography
      (OCT) in carotid artery stenting (CAS), to (2) highlight several instructive
      cases illustrating OCT-guidance as an interventional strategy, and to (3) present
      the largest case-series of OCT-guided CAS performed in North America,
      demonstrating its feasibility as an imaging modality in this setting. BACKGROUND:
      OCT is an intravascular imaging method that captures images with an axial
      resolution 10 times higher than intravascular ultrasound. OCT has proven to be a
      useful modality in coronary angiography and may have similar applications in
      evaluating carotid atherosclerotic disease. METHODS: We compared our experience
      in CAS utilizing OCT (40 patients) versus that of CAS without OCT guidance (52
      patients). RESULTS: No strokes or deaths occurred in either group
      postprocedurally or at 12 months. Fluoroscopy time was reduced in the OCT arm (14
      +/- 1 vs. 16 +/- 1 min). Postprocedural creatinine levels were identical (1 +/- 0
      mg/dl, P = 0.96). Procedure time (96 +/- 8 vs. 80 +/- 3 min, P = 0.06) and
      contrast use (94 +/- 4 vs. 83 +/- 4 ml, P = 0.05) was slightly elevated in the
      OCT arm. CONCLUSIONS: We established a standardized protocol to consistently
      obtain OCT images that helped guide interventional decision-making during CAS.
      OCT imaging in the carotids requires a higher contrast load and prolongs
      procedure time. However, it can be performed without significant increases in
      fluoroscopy time or negatively affecting renal function. There were no negative
      safety signals in this pilot study.

PMID- 29044928
TI  - A Rare Variant (rs933717) at FBXO31-MAP1LC3B in Chinese Is Associated With
      Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Recent evidence from genetic, cell biology, and animal model studies
      has suggested a pivotal role of autophagy in mediating systemic lupus
      erythematosus (SLE). However, the genetic basis has not yet been thoroughly
      examined. Therefore, the aim of the present study was to identify additional
      susceptibility variants in autophagy-related genes along with their functional
      significance. METHODS: First, we performed a gene family-based genetic
      association analysis in SLE patients with the use of ImmunoChip arrays, and then
      we selected the most strongly associated polymorphisms for replication in
      additional cohorts. To identify regulatory clues, we analyzed publicly available
      blood expression quantitative trait locus data and Encyclopedia of DNA Elements
      data on transcription factor binding sites and cell type-specific differential
      expression. Functional effects were tested by luciferase reporter assays,
      electrophoretic mobility shift assays, and differential gene expression assays.
      RESULTS: In 14,474 samples, we observed that the rare Chinese variant rs933717T
      was associated with susceptibility to SLE (0.11% in cases versus 0.87% in
      controls; P = 2.36 * 10-10 , odds ratio 0.13). The rs933717 risk allele C
      correlated with increased MAP1LC3B expression; increased MAP1LC3B messenger RNA
      was observed in SLE patients and in lupus-prone mice. In reporter gene
      constructs, the risk allele increased luciferase activity up to 2.7-3.8-fold in
      both HEK 293T and Jurkat cell lines, and the binding of HEK 293T and Jurkat cell
      nuclear extracts to the risk allele was also increased. CONCLUSION: We observed a
      likely genetic association between light chain 3B, a widely used marker for
      autophagy, and susceptibility to SLE.

PMID- 29044929
TI  - Anticancer activity of VmCT1 analogs against MCF-7 cells.
AB  - Antimicrobial peptides are considered promising drug candidates due to their
      broad range of activity. VmCT1 (Phe-Leu-Gly-Ala-Leu-Trp-Asn-Val-Ala-Lys-Ser-Val
      Phe-NH2 ) is an alpha-helical antimicrobial peptide that was obtained from the
      Vaejovis mexicanus smithi scorpion venom. Some of its analogs showed to be as
      antimicrobial as the wild type, and they were designed for understanding the
      influence of physiochemical parameters on antimicrobial and hemolytic activity.
      Some cationic antimicrobial peptides exhibit anticancer activity so VmCT1 analogs
      were tested to verify the anticancer activity of this family of peptides. The
      analogs were synthesized, purified, characterized, and the conformational studies
      were performed. The anticancer activity was assessed against MCF-7 mammary cancer
      cells. The results indicated that [Glu]7 -VmCT1-NH2 , [Lys]3 -VmCT1-NH2 , and
      [Lys]7 -VmCT1-NH2 analogs presented moderated helical tendency (0.23-0.61) and
      tendency of anticancer activity at 25 MUmol/L in 24 hr of experiment; and [Trp]9 
      VmCT1-NH2 analog that presented low helical tendency and moderated anticancer
      activity at 50 MUmol/L. These results demonstrated that single substitutions on
      VmCT1 led to different physicochemical features and could assist on the
      understanding of anticancer activity of this peptide family.

PMID- 29044930
TI  - Effect of incident nocturnal home hemodialysis versus incident continuous
      ambulatory peritoneal dialysis on employment rate, clinical, and laboratory
      outcomes: A 1-year retrospective observation study.
AB  - INTRODUCTION: While studies demonstrated favorable outcomes of nocturnal home
      hemodialysis (NHHD), direct comparison on employment rate, clinical and
      laboratory outcomes between the NHHD and continuous ambulatory peritoneal
      dialysis (CAPD) had not been previously performed. METHODS: A 1-year
      retrospective observation study was performed in 20 incidents alternate night
      NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic
      status, and Charlson comorbidity index matched, but not age due to our center's
      age limit for NHHD enrollment. The primary outcome was the difference in
      employment rate at 1 year. Secondary outcomes included differences in clinical
      parameters (weight, blood pressure, number of antihypertensive medication, dosage
      of phosphate binders, and erythropoietin stimulating agent) and laboratory
      parameters (residual renal function, mineral metabolic markers, hemoglobin).
      FINDINGS: NHHD subjects were 5 years younger than CAPD patients, and they had
      higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age-adjusted
      odds ratio for employment was 6.10 (95% confidence interval 1.77-20.99, P =
      0.04). They consumed less aluminum-based phosphate binder (0 vs. 1800 mg, P <
      0.01), but showed no significant disparities in other clinical parameters.
      Residual renal function in both groups declined comparably, nonetheless NHHD
      group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium
      phosphate product (3.13 vs. 4.12 mmol2 /L2 , P < 0.01), with similar hemoglobin
      levels. DISCUSSION: NHHD appeared to offer higher employment rate, lower dosage
      of aluminum-based phosphate binder and mineral metabolic markers at 1 year
      compared with CAPD in Hong Kong.

PMID- 29044931
TI  - A novel technique for simultaneous hemostasis of ipsilateral radial and ulnar
      artery access sites.
AB  - With the increased use of transradial artery access (TRA) for diagnostic and
      coronary interventional procedures, crossover to the ipsilateral ulnar artery
      after TRA failure is being reported more frequently. A major challenge with
      ipsilateral transradial and ulnar artery access is achieving efficient patent
      hemostasis of both the radial and ulnar arteries at the completion of the
      procedure. In this report, we describe two cases of failed TRA with subsequent
      ipsilateral ulnar artery access. A novel and practical technique of simultaneous
      patent hemostasis of both the ipsilateral radial and ulnar artery access sites is
      described, using a QuikClot(r) Radial(r) hemostasis pad and a TR Band(r) .

PMID- 29044933
TI  - Cross-Tissue Identification of Somatic Stem and Progenitor Cells Using a Single
      Cell RNA-Sequencing Derived Gene Signature.
AB  - A long-standing question in biology is whether multipotent somatic stem and
      progenitor cells (SSPCs) feature molecular properties that could guide their
      system-independent identification. Population-based transcriptomic studies have
      so far not been able to provide a definite answer, given the rarity and
      heterogeneous nature of these cells. Here, we exploited the resolving power of
      single-cell RNA-sequencing to develop a computational model that is able to
      accurately distinguish SSPCs from differentiated cells across tissues. The
      resulting classifier is based on the combined expression of 23 genes including
      known players in multipotency, proliferation, and tumorigenesis, as well as novel
      ones, such as Lcp1 and Vgll4 that we functionally validate in intestinal
      organoids. We show how this approach enables the identification of stem-like
      cells in still ambiguous systems such as the pancreas and the epidermis as well
      as the exploration of lineage commitment hierarchies, thus facilitating the study
      of biological processes such as cellular differentiation, tissue regeneration,
      and cancer. Stem Cells 2017;35:2390-2402.

PMID- 29044932
TI  - Right heart dysfunction and failure in heart failure with preserved ejection
      fraction: mechanisms and management. Position statement on behalf of the Heart
      Failure Association of the European Society of Cardiology.
AB  - There is an unmet need for effective treatment strategies to reduce morbidity and
      mortality in patients with heart failure with preserved ejection fraction
      (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively
      focused on the left side. However, it is now increasingly recognized that right
      heart dysfunction is common and contributes importantly to poor prognosis in
      HFpEF. More insights into the development of right heart dysfunction in HFpEF may
      aid to our knowledge about this complex disease and may eventually lead to better
      treatments to improve outcomes in these patients. In this position paper from the
      Heart Failure Association of the European Society of Cardiology, the Committee on
      Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis,
      and pathophysiology of right heart dysfunction and failure in patients with
      HFpEF. Finally, potential treatment strategies, important knowledge gaps and
      future directions regarding the right side in HFpEF are discussed.

PMID- 29044934
TI  - Aqueous Gold Overgrowth of Silver Nanoparticles: Merging the Plasmonic Properties
      of Silver with the Functionality of Gold.
AB  - To date, it has not been possible to combine the high optical quality of silver
      particles with the good chemical stability and synthetic convenience in a fully
      aqueous system, while simultaneously allowing chemical surface functionalization.
      We present a synthetic pathway for future developments in information, energy and
      medical technology where strong optical/electronic properties are crucial.
      Therefore, the advantages inherent to gold are fused with the plasmonic
      properties of silver in a fully aqueous Au/Ag/Au core-shell shell system. These
      nanoparticles inherit low dispersity from their masked gold cores, yet
      simultaneously exhibit the strong plasmonic properties of silver. Protecting the
      silver surface with a thin gold layer enables oxidant stability and functionality
      without altering the Ag-controlled optical properties. This combines both worlds
      optical quality and chemical stability-and is not limited to a specific particle
      shape.

PMID- 29044935
TI  - Unusual presentation of metastatic gastrointestinal stromal tumour.

PMID- 29044936
TI  - MMP1 and MMP3 gene polymorphisms in patients with acute coronary syndromes.
AB  - Matrix metalloproteinases (MMPs) are the group of proteolytic enzymes that break
      down the components of the connective tissue matrix leading to unstable
      atherosclerotic plaques. The aim of this study was to examine the association
      between MMP1-1607dupG (rs1799750) and MMP3-1171dupA (rs3025058) gene
      polymorphisms and acute coronary syndromes (ACS) in the form of unstable angina.
      This study included 197 patients with ACS in the form of unstable angina
      confirmed by coronary angiography (defined by >70% stenosis in at least one major
      coronary artery) and 144 healthy controls. There was no statistically significant
      difference in the distribution of the MMP1-1607dupG (rs1799750) polymorphism
      between patients with unstable angina and the control group. With regard to the
      MMP3-1171dupA (rs3025058) polymorphism, a significant increase in the frequency
      of the 6A/6A genotype among patients with unstable angina was detected. This
      association was confirmed in multivariate logistic regression analysis, where
      male sex and rs3025058 6A/6A genotype were significantly associated with an
      increased risk of ACS. (c) 2017 IUBMB Life, 69(11):850-855, 2017.

PMID- 29044937
TI  - Selective inhibition of M5 muscarinic acetylcholine receptors attenuates cocaine
      self-administration in rats.
AB  - Cocaine use disorder (CUD) remains a debilitating health problem in the United
      States for which there are no Food and Drug Administration-approved treatment
      options. Accumulating anatomical and electrophysiological evidence indicates that
      the muscarinic acetylcholine receptor (mAChR) subtype 5 (M5 ) plays a critical
      role in the regulation of the mesolimbic dopaminergic reward circuitry, a major
      site of action for cocaine and other psychostimulants. In addition, M5 knockout
      mice exhibit reduced cocaine self-administration behaviors with no differences in
      sugar pellet-maintained responding relative to wild-type mice. These findings
      suggest that selective inhibition of M5 mAChR may provide a novel pharmacological
      approach for targeting CUD. Recently, we reported the synthesis and
      characterization of ML375, a selective negative allosteric modulator (NAM) for
      the rat and human M5 mAChR with optimized pharmacokinetic properties for systemic
      dosing in rodents. In the present study, male Sprague-Dawley rats were trained to
      self-administer intravenous cocaine (0.1-0.75 mg/kg/infusion) under a 10-response
      fixed ratio or a progressive ratio schedule of reinforcement. Under both
      schedules of reinforcement, ML375 produced dose-related reductions in cocaine
      self-administration. ML375 also modestly reduced sugar pellet-maintained
      responding on the 10-response, fixed ratio schedule but had no effect under a
      progressive ratio schedule of reinforcement. Further, ML375 did not affect
      general motor output as assessed by a rotarod test. Collectively, these results
      provide the first demonstration that selective inhibition of M5 using the M5 NAM
      ML375 can attenuate both the reinforcing effects and the relative strength of
      cocaine and suggest that M5 NAMs may represent a promising, novel treatment
      approach for CUD.

PMID- 29044938
TI  - Hot Off the Press: Prehospital Advanced Cardiac Life Support for Out-of-hospital
      Cardiac Arrest.
AB  - This retrospective cohort study examined the rate of survival to hospital
      discharge among adult patients with out-of-hospital cardiac arrest, comparing
      patients who received care only from basic cardiac life support (BCLS)-trained
      emergency medical service (EMS) crews to patients who had an advanced cardiac
      life support (ACLS)-trained EMS crew on scene at some point during the
      resuscitation. There was no difference in the primary outcome of rate of survival
      to hospital discharge (10.9% with ACLS care and 10.6% with BCLS care, p = 0.67).

PMID- 29044939
TI  - Synthesis and characterization of high quantum yield and oscillator strength 6
      chloro-2-(4-cynophenyl)-4-phenyl quinoline (cl-CN-DPQ) organic phosphor for solid
      state lighting.
AB  - A novel blue luminescent 6-chloro-2-(4-cynophenyl) substituted diphenyl quinoline
      (Cl-CN DPQ) organic phosphor has been synthesized by the acid-catalyzed
      Friedlander reaction and then characterized to confirm structural, optical and
      thermal properties. Structural properties of Cl-CN-DPQ were analyzed by Fourier
      transform infrared (FTIR), nuclear magnetic resonance (NMR) spectroscopy, X-ray
      diffraction technique (XRD) and scanning electron microscopy (SEM) and energy
      dispersive analysis of X-ray (EDAX) spectroscopy. FTIR spectra confirmed the
      presence of different functional groups and bond stretching. 1 H-NMR and 13 C-NMR
      confirmed the formation of an organic Cl-CN-DPQ compound. X-ray diffraction study
      provided its crystalline nature. The surface morphology of Cl-CN-DPQ was analyzed
      by SEM, while EDAX spectroscopy revealed the elemental analysis. Differential
      thermal analysis (TGA/DTA) disclosed its thermal stability up to 250 degrees C.
      The optical properties of Cl-CN-DPQ were investigated by UV-vis absorption and
      photoluminescence (PL) measurements. Cl-CN-DPQ exhibits intense blue emission at
      434 nm in a solid-state crystalline powder with CIE co-ordinates (0.157, 0.027),
      when excited at 373 nm. Cl-CN-DPQ shows remarkable Stokes shift in the range
      14800-5100 cm-1 , which is the characteristic feature of intense light emission.
      A narrow full width at half-maximum (FWHM) value of PL spectra in the range 42-48
      nm was observed. Oscillator strength, energy band gap, quantum yield, and
      fluorescence energy yield were also examined using UV-vis absorption and
      photoluminescence spectra. These results prove its applications towards
      developing organic luminescence devices and displays, organic phosphor-based
      solar cells and displays, organic lasers, chemical sensors and many more.

PMID- 29044940
TI  - Low intrapatient variability of histomorphological findings in periprosthetic
      tissues from revised metal/ceramic on polyethylene joint arthroplasties.
AB  - The type of tissue response to implant by-products can be determined by
      examination of periprosthetic tissues. However, little is known about the most
      suitable location for tissue sampling. The main goal of this study was to
      evaluate the extent of variability in tissue response in relation to location of
      tissue sampling, implant fixation, age and sex in total joint arthroplasties with
      metal-on-polyethylene or ceramic-on-polyethylene bearing pairs. We processed 236
      histology slides from 21 patients and focused on the association between the
      location of tissue samples and histological features. The presence of the
      synovial hyperplasia showed a significant association with the particular
      sampling site. A higher density of high endothelial cell venules was seen in the
      samples from around the joint, and polyethylene particles were more abundant in
      noncemented TJA but both findings did not show statistically significant
      association with the sampling site. The results showed a relatively small
      variance in the tissue response to prosthetic by-products among tissues sampled
      from the same patient. Our findings indicate that tissue samples retrieved from
      similar distance from around the TJA during the revision operation show
      comparable results of histological analysis. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 106B: 2008-2018, 2018.

PMID- 29044941
TI  - Clinical significance of changes in systemic inflammatory markers and
      carcinoembryonic antigen levels in predicting metastatic colorectal cancer
      prognosis and chemotherapy response.
AB  - AIM: Metastatic colorectal cancer (mCRC) is associated with poor prognosis, and
      biomarkers are required for predicting survival and chemotherapy response. This
      study aimed to evaluate the significance of changes in systemic inflammatory
      markers and carcinoembryonic antigen (CEA) levels in predicting mCRC prognosis
      and chemotherapy response. METHODS: In this retrospective study, 503 patients who
      received first-line palliative chemotherapy for mCRC between 2008 and 2014 at a
      tertiary hospital in Korea were evaluated. Changes in neutrophil-to-lymphocyte
      ratio (NLR) and modified Glasgow prognostic score (mGPS) were divided into low-to
      low, high-to-low, low-to-high and high-to-high groups. The CEA response was
      defined as CEA-complete response (CEA normalization), CEA-partial response (>=50%
      decrease in CEA levels), CEA-progressive disease (>=50% increase in CEA levels)
      and CEA-stable disease. Overall survival (OS) and progression-free survival (PFS)
      were evaluated according to NLR, mGPS and CEA levels. RESULTS: High
      prechemotherapy NLR, mGPS and CEA levels independently predicted poor survival
      and chemotherapy response. Continuously high NLR or change to high NLR was also
      associated with poor OS and PFS; however, continuously low NLR or reduced NLR
      showed good prognosis. CEA response was also an independent prognostic marker for
      OS and PFS. High NLR and mGPS were correlated with elevated CEA levels.
      CONCLUSION: Inflammatory marker levels were significantly associated with CEA
      levels. The prechemotherapy levels of systemic inflammatory markers and CEA were
      associated with OS or PFS. The change patterns in NLR and CEA levels can be
      utilized as prognostic and predictive markers for chemotherapy response.

PMID- 29044942
TI  - Highly luminescent nitrogen-doped carbon dots for simultaneous determination of
      chlortetracycline and sulfasalazine.
AB  - Here, we have presented a green and facile strategy to fabricate nitrogen-doped
      carbon dots (N-CDs) and their applications for determination of chlortetracycline
      (CTC) and sulfasalazine (SSZ). The fluorescent N-CDs, prepared by one-step
      hydrothermal reaction of citric acid and l-arginine, manifested numerous
      excellent features containing strong blue fluorescence, good water-solubility,
      narrow size distribution, and a high fluorescence quantum yield (QY) of 38.8%.
      Based on the fluorescence quenching effects, the as-synthesized N-CDs as a
      fluorescent nanosensor exhibited superior analytical performances for quantifying
      CTC and SSZ. The linear range for CTC was calculated to be from 0.85 to 20.38 MUg
      ml-1 with a low detection limit of 0.078 MUg ml-1 . Meanwhile, the linear range
      for SSZ was estimated to be from 0.34 to 6.76 MUg ml-1 with a low detection limit
      of 0.032 MUg ml-1 . Therefore, the N-CDs hold admirable application potential for
      constructing a fluorescent sensor for pharmaceutical analysis.

PMID- 29044943
TI  - Fast Lithium-Ion Transportation in Crystalline Polymer Electrolytes.
AB  - Fast lithium-ion transportation is found in the crystalline polymer electrolytes,
      alpha-CD-PEOn /Li+ (n=12, 40), prepared by self-assembly of alpha-cyclodextrin
      (CD), polyethylene oxide (PEO) and Li+ salts. A detailed solid-state NMR study
      combined with the X-ray diffraction technique reveals the unique structural
      features of the samples, that is, a) the tunnel structure formed by the assembled
      CDs, providing the ordered long-range pathway for Li+ ion transportation; b) the
      all-trans conformational sequence of the PEO chains in the tunnels, attenuating
      significantly the coordination between Li+ and the EO segments. The origin of the
      fast lithium-ion transportation has been attributed to these unique structural
      features. This work demonstrates the first example in solid polymer electrolytes
      (SPEs) for "creating" fast ion transportation through material design and will
      find potential applications in the design of new ionconducting SPE materials.

PMID- 29044944
TI  - Rapid evolution of phenology during range expansion with recent climate change.
AB  - Although climate warming is expected to make habitat beyond species' current cold
      range edge suitable for future colonization, this new habitat may present an
      array of biotic or abiotic conditions not experienced within the current range.
      Species' ability to shift their range with climate change may therefore depend on
      how populations evolve in response to such novel environmental conditions.
      However, due to the recent nature of thus far observed range expansions, the role
      of rapid adaptation during climate change migration is only beginning to be
      understood. Here, we evaluated evolution during the recent native range expansion
      of the annual plant Dittrichia graveolens, which is spreading northward in Europe
      from the Mediterranean region. We examined genetically based differentiation
      between core and edge populations in their phenology, a trait that is likely
      under selection with shorter growing seasons and greater seasonality at northern
      latitudes. In parallel common garden experiments at range edges in Switzerland
      and the Netherlands, we grew plants from Dutch, Swiss, and central and southern
      French populations. Population genetic analysis following RAD-sequencing of these
      populations supported the hypothesized central France origins of the Swiss and
      Dutch range edge populations. We found that in both common gardens, northern
      plants flowered up to 4 weeks earlier than southern plants. This differentiation
      in phenology extended from the core of the range to the Netherlands, a region
      only reached from central France over approximately the last 50 years. Fitness
      decreased as plants flowered later, supporting the hypothesized benefits of
      earlier flowering at the range edge. Our results suggest that native range
      expanding populations can rapidly adapt to novel environmental conditions in the
      expanded range, potentially promoting their ability to spread.

PMID- 29044945
TI  - meso-Aryl [20]pi Homoporphyrin: The Simplest Expanded Porphyrin with the Smallest
      Mobius Topology.
AB  - An unstable conjugated homoporphyrin was successfully stabilized by introducing
      meso-aryl substitutents. It was evident from the moderate diatropic ring current
      found by NMR analysis that the newly formed 20pi conjugated free base and its
      protonated form exhibited Mobius aromatic character. Furthermore, complexation as
      a ligand with an RhI ion afforded a unique binding mode and retained the Mobius
      aromaticity. Overall, these compounds are the smallest Mobius aromatic molecules,
      as confirmed by spectral and crystal-structure analysis and supported by
      theoretical studies.

PMID- 29044946
TI  - Aquaporin-1 inhibition reduces metastatic formation in a mouse model of melanoma.
AB  - Aquaporin-1 (AQP1) is a proangiogenic water channel protein promoting endothelial
      cell migration. We previously reported that AQP1 silencing by RNA interference
      reduces angiogenesis-dependent primary tumour growth in a mouse model of
      melanoma. In this study, we tested the hypothesis that AQP1 inhibition also
      affects animal survival and lung nodule formation. Melanoma was induced by
      injecting B16F10 cells into the back of C57BL6J mice. Intratumoural injection of
      AQP1 siRNA and CTRL siRNA was performed 10 days after tumour cell implantation.
      Lung nodule formation was analysed after the death of the mice. Western blot was
      used to quantify HIF-1alpha, caspase-3 (CASP3) and metalloproteinase-2 (MMP2)
      protein levels. We found that AQP1 knock-down (KD) strongly inhibited metastatic
      lung nodule formation. Moreover, AQP1 siRNA-treated mice showed a twofold
      survival advantage compared to mice receiving CTRL siRNAs. The reduced AQP1
      dependent tumour angiogenesis caused a hypoxic condition, evaluated by HIF-1alpha
      significant increase, in turn causing an increased level of apoptosis in AQP1 KD
      tumours, assessed by CASP3 quantification and DNA fragmentation. Importantly, a
      decreased level of MMP2 after AQP1 KD indicated a decreased activity against
      extracellular matrix associated with reduced vascularization and metastatic
      formation. In conclusion, these findings highlight an additional role for AQP1 as
      an important determinant of tumour dissemination by facilitating tumour cell
      extravasation and metastatic formation. This study adds knowledge on the role
      played by AQP1 in tumour biology and supports the view of AQP1 as a potential
      drug target for cancer therapy.

PMID- 29044947
TI  - Partial characterization of phylogeny, ecology and function of the fibrolytic
      bacterium Ruminococcus flavefaciens OS14, newly isolated from the rumen of swamp
      buffalo.
AB  - The fibrolytic rumen bacterium Ruminococcus flavefaciensOS14 was isolated from
      swamp buffalo and its phylogenetic, ecological and digestive properties were
      partially characterized. Isolates from rumen contents of four swamp buffalo were
      screened for fibrolytic bacteria; one of the 40 isolates showed a distinctive
      feature of solubilizing cellulose powder in liquid culture and was identified as
      R. flavefaciens based on its 16S ribosomal DNA sequence. This isolate, OS14, was
      employed for detection and digestion studies, for which a quantitative PCR assay
      was developed and defined cultures were tested with representative forages in
      Thailand. OS14 was phylogenetically distant from other isolated and uncultured R.
      flavefaciens and showed limited distribution among Thai ruminants but was absent
      in Japanese cattle. OS14 digested rice straw and other tropical forage to a
      greater extent than the type strain C94 of R. flavefaciens. OS14 produced more
      lactate than C94, and digested para grass to produce propionate more extensively
      in co-culture with lactate-utilizing Selenomonas ruminantium S137 than a co
      culture of C94 with S137. These results indicate that phylogenetically distinct
      OS14 could digest Thai local forage more efficiently than the type strain,
      possibly forming a symbiotic cross-feeding relationship with lactate-utilizing
      bacteria. This strain might be useful for future animal and other industrial
      applications.

PMID- 29044948
TI  - Intracellular pathway and subsequent transformation of hydroxyapatite
      nanoparticles in the SAOS-2 osteoblast cell line.
AB  - Internalization of hydroxyapatite nanoparticles in SAOS-2 osteoblasts for 2 and
      24 h was investigated in vitro using 5 and 50 ug/mL nanoparticles in culture
      medium. No cytotoxic effects were observed in a PrestoBlue viability assay.
      Focused ion beam-scanning electron microscopy and transmission electron
      microscopy were used to study nanoparticle trafficking inside cells and to
      characterize the physicochemical properties of the remodeled nanoparticles.
      Nanoparticles were actively internalized by cells and maintained in intracellular
      membrane-bound compartments. Dissolution of hydroxyapatite nanoparticles was
      observed inside phagolysosome in all samples. After 24 h of internalization in
      cell culture assays, reprecipitation of calcium phosphate minerals was observed
      in membrane-bound compartments in 5 and 50 ug/mL samples. Compared to the
      original nanoparticles, the reprecipitated calcium phosphate phase presented a
      different morphology, structure, and chemical composition. Two sample preparation
      methods were used and confirmed that reprecipitation of the calcium phosphate
      crystallites occurred in the intracellular environment and not during electron
      microscopy sample preparation. Reprecipitation of calcium phosphate prevented the
      release of large amounts of calcium and phosphate ions inside the cells. This
      phenomenon may be linked to physiological processes in the cell that control the
      concentration and trafficking of intracellular calcium ions, which are highly
      controlled by cells. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 428-439, 2018.

PMID- 29044949
TI  - Induction of erythropoietin gene expression in epithelial cells by chemicals
      identified in GATA inhibitor screenings.
AB  - Erythropoietin (EPO) is a hormone that promotes proliferation, differentiation
      and survival of erythroid progenitors. EPO gene expression is regulated in a
      tissue-specific and hypoxia-inducible manner and is mainly restricted to renal
      EPO-producing cells after birth. Chronic kidney disease (CKD) confers high risk
      for renal anemia due to lower EPO production from injured kidneys. In transgenic
      reporter lines of mice, disruption of a GATA-binding motif within the Epo gene
      promoter-proximal region restores constitutive reporter expression in epithelial
      cells. Here, mitoxantrone and its analogues, identified as GATA factor inhibitors
      through high-throughput chemical library screenings, markedly induce EPO/Epo gene
      expression in epithelium-derived cell lines and mice regardless of oxygen levels.
      In contrast, mitoxantrone interferes with hypoxia-induced EPO gene expression in
      Hep3B cells. Cryptic promoters are created for the EPO/Epo gene expression in
      epithelial cells upon mitoxantrone treatment, and consequently, unique 5'
      untranslated regions are generated. The mitoxantrone-induced aberrant transcripts
      contribute to the reporter protein production in epithelial cells that carry the
      reporter gene in the proper reading frame of mouse Epo gene. Thus, EPO production
      in uninjured adult epithelial cells may be a therapeutic approach for renal
      anemia in patients with CKD.

PMID- 29044950
TI  - Biochemical characterization of argininosuccinate lyase from M. tuberculosis:
      significance of a c-terminal cysteine in catalysis and thermal stability.
AB  - Arginine biosynthesis pathway is crucial to the survival and pathogenesis of
      Mycobacterium tuberculosis (Mtb). Arginine is a critical amino acid that
      contributes to the inflection of cellular immune responses during pathogenesis.
      Argininosuccinate lyase from Mtb (MtArgH), the last enzyme in the pathway,
      catalyzes the production of arginine from argininosuccinic acid. MtArgH is an
      essential enzyme for the growth and survival of M. tuberculosis. We biochemically
      characterized MtArgH and deciphered the role of a previously unexplored cysteine
      (Cys441 ) residue at the C-terminal region of the protein. Chemical modification
      of Cys441 completely abrogated the enzymatic activity suggesting its involvement
      in the catalytic mechanism. Replacement of Cys441 to alanine showed a striking
      decrease in the enzymatic activity, while retaining the overall secondary to
      quaternary structure of the protein, hence corroborating the involvement of
      Cys441 in the process of catalysis. Interestingly, replacement of Cys441 to
      serine, showed significant increase in activity, as compared to the wild-type
      MtArgH. Inactivity of C441 A and elevated activity of its conservative mutant
      (C441 S) confirmed the participation of Cys441 in the MtArgH activity. We also,
      observed that C441 S mutant has higher thermal stability and maintains
      significant activity at high temperatures. This is in concordance with our
      observation that Cys441 in Mtb is replaced by a serine in the ArgH from
      thermophilic microorganisms. Furthermore, we also propose a potential feedback
      mechanism, wherein the Cys441 is covalently modified to S-(2-succinyl) cysteine
      (succination) by one of the products, fumarate, thereby inactivating MtArgH.
      These insights into the mechanism of MtArgH activity unravel novel regulations of
      arginine biosynthetic pathway in Mtb. (c) 2017 IUBMB Life, 69(11):896-907, 2017.

PMID- 29044952
TI  - Protocol for Computational Enzymatic Reactivity Based on Geometry Optimisation.
AB  - Enzymes play a biologically essential role in performing and controlling an
      important share of the chemical processes occurring in life. However, despite
      their critical role in nature, attaining a clear understanding of the way an
      enzyme acts is still cumbersome. Computational enzymology is playing an
      increasingly important role in this field of research. It allows the elucidation
      of a complete and detailed mechanism of an enzymatic reaction, including the
      characterization of reaction intermediates and transition states from both
      structural and energetic points of view, which is something that no other single
      experiment can produce alone. In this review, we present a general computational
      strategy to study enzymatic mechanisms based on adiabatic mapping and free
      geometry optimization. These methods allow chemical reactions to be studied with
      high theoretical levels, and allow a more exhaustive exploration of the chemical
      reactional space than other available methods, albeit being limited to the extent
      that they explore the enzyme conformational space. Special attention is given to
      the choice of the theoretical levels, as well as describing the model systems
      that are currently used to study enzymatic reactions. With this, we aim to
      provide a good introduction for non-specialised users in this field of research.
      We also provide a selection of hand-picked examples from our own work that
      illustrate the power of computational enzymology to study catalytic mechanisms.
      Some of these studies constitute pioneering work in the field that were later
      validated by experimental means.

PMID- 29044951
TI  - A Chemoenzymatic Histology Method for O-GlcNAc Detection.
AB  - Modification of nuclear and cytoplasmic proteins by the addition or removal of O
      GlcNAc dynamically impacts multiple biological processes. Here, we present the
      development of a chemoenzymatic histology method for the detection of O-GlcNAc in
      tissue specimens. We applied this method to screen murine organs, uncovering
      specific O-GlcNAc distribution patterns in different tissue structures. We then
      utilized our histology method for O-GlcNAc detection in human brain specimens
      from healthy donors and donors with Alzheimer's disease and found higher levels
      of O-GlcNAc in specimens from healthy donors. We also performed an analysis using
      a multiple cancer tissue array, uncovering different O-GlcNAc levels between
      healthy and cancerous tissues, as well as different O-GlcNAc cellular
      distributions within certain tissue specimens. This chemoenzymatic histology
      method therefore holds great potential for revealing the biology of O-GlcNAc in
      physiopathological processes.

PMID- 29044953
TI  - Preparation and evaluation of diblock copolymer-grafted silica by sequential
      surface initiated-atom transfer radical polymerization for reverse-phase/ion
      exchange mixed-mode chromatography.
AB  - A novel approach that involved the grafting of diblock copolymer with two types
      of monomer onto substrate by sequential surface initiated-atom transfer radical
      polymerization was proposed to prepare a mixed-mode chromatographic stationary
      phase. The distinguishing feature of this method is that it can be applied in the
      preparation of various mixed-mode stationary phases. In this study, a new reverse
      phase/ion-exchange stationary phase was prepared by grafting hydrophobic styrene
      and cationic sodium 4-styrenesulfonate by the proposed approach onto silica
      surface. The chromatographic properties of the prepared stationary phase were
      evaluated by the separation of benzene derivatives, anilines, and beta-agonists,
      and by the effect of pH values and acetonitrile content on the retention.
      Compared with typical RP columns, the prepared stationary phase achieved the
      better resolution and higher selectivity at a shorter separation time and lower
      organic content. Moreover, the application of the prepared column was proved by
      separating widely distributed polar and charged compounds simultaneously.

PMID- 29044954
TI  - C3 -Symmetric Tricyclo[2.2.1.02,6 ]heptane-3,5,7-triol.
AB  - A straightforward access to a hitherto unknown C3 -symmetric tricyclic triol both
      in racemic and enantiopure forms has been developed. Treatment of 7-tert
      butoxynorbornadiene with peroxycarboxylic acids provided mixtures of C1 - and C3 
      symmetric 3,5,7-triacyloxynortricyclenes via transannular pi-cyclization and
      replacement of the tert-butoxy group. By refluxing in formic acid, the C1 
      symmetric esters were converted to the C3 -symmetric formate. Hydrolysis gave
      diastereoisomeric triols, which were separated by recrystallization. Enantiomer
      resolution via diastereoisomeric tri(O-methylmandelates) delivered the target
      triols on a gram scale. The pure enantiomers are useful as core units of dopants
      for liquid crystals.

PMID- 29044955
TI  - Single-Molecule Observation of the Photoregulated Conformational Dynamics of DNA
      Origami Nanoscissors.
AB  - We demonstrate direct observation of the dynamic opening and closing behavior of
      photocontrollable DNA origami nanoscissors using high-speed atomic force
      microscopy (HS-AFM). First the conformational change between the open and closed
      state controlled by adjustment of surrounding salt concentration could be
      directly observed during AFM scanning. Then light-responsive moieties were
      incorporated into the nanoscissors to control these structural changes by
      photoirradiation. Using photoswitchable DNA strands, we created a photoresponsive
      nanoscissors variant and were able to distinguish between the open and closed
      conformations after respective irradiation with ultraviolet (UV) and visible
      (Vis) light by gel electrophoresis and AFM imaging. Additionally, these
      reversible changes in shape during photoirradiation were directly visualized
      using HS-AFM. Moreover, four photoswitchable nanoscissors were assembled into a
      scissor-actuator-like higher-order object, the configuration of which could be
      controlled by the open and closed switching induced by irradiation with UV and
      Vis light.

PMID- 29044956
TI  - Can we talk about our fears?

PMID- 29044957
TI  - Comment on the treatment of high-grade internal rectal prolapse by laparoscopic
      ventral rectopexy.

PMID- 29044958
TI  - A simple validated multi-analyte method for detecting drugs in oral fluid by
      ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
AB  - A UPLC-MS/MS method was developed to identify and quantitate 37 commonly abused
      drugs in oral fluid. Drugs of interest included amphetamines, benzodiazepines,
      cocaine, opiates, opioids, phencyclidine and tetrahydrocannabinol. Sample
      preparation and extraction are simple, and analysis times short. Validation
      showed satisfactory performance at relevant concentrations. The possibility of
      contaminated samples as well as the interpretation in relation to well-knows
      matrices, such as urine, will demand further study.

PMID- 29044959
TI  - A General Strategy Assisted with Dual Reductants and Dual Protecting Agents for
      Preparing Pt-Based Alloys with High-Index Facets and Excellent Electrocatalytic
      Performance.
AB  - Synthesizing noble metallic nanoparticles (NPs) enclosed by high-index facets
      (HIFs) is challenged as it involves the tuning of growth kinetics, the selective
      adsorption of certain chemical species, and the epitaxial growth from HIF
      enclosed seeds. Herein, a simple and general strategy is reported by using dual
      reduction agents and dual capping agents to prepare Pt-based alloy NPs with HIFs,
      in which both glycine and poly(vinylpyrrolidone) serve as the reductants and
      capping agents. Due to the facilely tunable growth/nucleation rates and
      protecting abilities of the reductants and capping agents, Pt concave nanocube
      (CNC), binary Pt-Ni CNC, ternary Pt-Mn-Cu CNC, and Pt-Mn-Cu ramiform polyhedron
      alloy NPs terminated by HIFs as well as other NPs with well-defined morphologies
      such as Pt-Mn-Cu nanocube and Pt-Mn-Cu nanoflower are obtained with this
      approach. Owing to the high density of low-coordinated Pt sites (HIF structure)
      and the unique electronic effect of Pt-Mn-Cu ternary alloys, the as-prepared Pt
      Mn-Cu NPs show enhanced catalytic activity toward methanol and formic acid
      electro-oxidation reactions with excellent stability. This work provides a
      promising methodology for designing and fabricating Pt-based alloy NPs as
      efficient fuel cell catalyst.

PMID- 29044960
TI  - Primary peritoneal carcinosarcoma in a dialysis patient.

PMID- 29044962
TI  - High anion gap metabolic acidosis: A case of pyroglutamic acidosis.

PMID- 29044961
TI  - Donor-derived renal mixed fungal infections in cardiac death donor kidney
      transplant recipients.

PMID- 29044963
TI  - Using SDS-PAGE gel fingerprinting to identify soft-bodied wood-boring insect
      larvae to species.
AB  - BACKGROUND: This paper describes the progress that we have made in assessing the
      feasibility of 'fingerprinting' using imaged SDS-PAGE gels of haemolymph
      proteins, to identify soft-bodied wood-boring insect larvae such as the Asian
      longhorn beetle, Anoplophora glabripennis (Motscholsky, 1853) (Coleoptera:
      Cerambycidae). Because of stringent import restrictions and difficulty in
      obtaining licences to work with these organisms, we opted to work with four
      species of scarab beetle, Mecynorhina polyphemus (Fabricius, 1781), Pachnoda
      sinuata (Fabricius, 1775), Eucidella shiratica (Csiki, 1909) and Eucidella
      shultzeorum (Kolbe, 1906) which have near identical larval morphologies. RESULTS:
      We show that this technology when combined with an advanced pattern matching
      system (Digital Automated Identification SYstem - DAISY) can classify soft-bodied
      insect larvae that are almost identical morphologically to species at a level of
      accuracy is in excess of 98%. The study also indicates that the technology copes
      well with noisy data and small training sets. CONCLUSION: The experience gained
      in undertaking this study gives us confidence that we will be able to develop a
      field deployable system in the medium term. We believe that as a high-throughput
      identification tool, this technology is superior to competitor technologies (e.g.
      fingerprinting of imaged DNA gels) in terms of speed, cost and ease of use; and
      therefore, is suitable for low-cost deployment in the field. (c) 2017 Society of
      Chemical Industry.

PMID- 29044964
TI  - Interventional cardiologists: Beware and be aware: An updated report of radiation
      induced cutaneous cancers.
AB  - We describe 5 years of follow-up of a previously reported case of disabling
      ionizing radiation (IR)-related cutaneous cancer in a high-volume interventional
      cardiologist. This case illustrates the cycle of exposure, disease, remission,
      and re-exposure that demonstrates the cause-and-effect relationship between
      radiation exposure and cutaneous cancer. Prior cautions for working in
      environments with radiation exposure emphasized strict adherence to the ALARA
      principle and called for improved radiation protection equipment. New studies
      stress that radiation exposure should be as near to zero as possible and place a
      call for research and technologies that mitigate the use of IR for all
      interventionists.

PMID- 29044965
TI  - Breaking Bonds and Forming Nanographene Diradicals with Pressure.
AB  - New anthanthrone-based polycyclic scaffolds possessing peripheral crowded
      quinodimethanes have been prepared. While the compounds adopt a closed-shell
      butterfly-shaped structure in the ground state, a curved-to-planar fluxional
      inversion is accessible with a low energy barrier through a biradicaloid
      transition state. Inversion is primarily driven by the release of strain
      associated with steric hindrance at the peri position of the anthanthrone core; a
      low-lying diradical state is accessible through planarization of the core, which
      is attained in solution at moderate temperatures. The most significant aspect of
      this transformation is that planarization is also achieved by application of mild
      pressure in the solid state, wherein the diradical remains kinetically trapped.
      Complementary information from quantum chemistry, 1 H NMR, and Raman
      spectroscopies, together with magnetic experiments, is consistent with the
      formation of a nanographene-like structure that possesses radical centers
      localized at the exo-anthanthrone carbons bearing phenyl substituents.

PMID- 29044966
TI  - V1b vasopressin receptor trafficking and signaling: Role of arrestins, G proteins
      and Src kinase.
AB  - The signaling pathway of G protein-coupled receptors is strongly linked to their
      trafficking profile. Little is known about the molecular mechanisms involved in
      the vasopressin receptor V1b subtype (V1b R) trafficking and its impact on
      receptor signaling and regulation. For this purpose, we investigated the role of
      beta-arrestins in receptor desensitization, internalization and recycling and
      attempted to dissect the V1b R-mediated MAP kinase pathway. Using MEF cells
      Knocked-out for beta-arrestins 1 and 2, we demonstrated that both beta-arrestins
      1 and 2 play a fundamental role in internalization and recycling of V1b R with a
      rapid and transient V1b R-beta-arrestin interaction in contrast to a slow and
      long-lasting beta-arrestin recruitment of the V2 vasopressin receptor subtype (V2
      R). Using V1b R-V2 R chimeras and V1b R C-terminus truncations, we demonstrated
      the critical role of the V1b R C-terminus in its interaction with beta-arrestins
      thereby regulating the receptor internalization and recycling kinetics in a
      phosphorylation-independent manner. In parallel, V1b R MAP kinase activation was
      dependent on arrestins and Src-kinase but independent on G proteins.
      Interestingly, Src interacted with hV1b R at basal state and dissociated when
      receptor internalization occurred. Altogether, our data describe for the first
      time the trafficking profile and MAP kinase pathway of V1b R involving both
      arrestins and Src kinase family.

PMID- 29044967
TI  - Comparison of long-term outcomes of 50 and 100 mg rt-PA in the management of
      acute pulmonary thromboembolism.
AB  - BACKGROUND: Pulmonary thromboembolism (PTE) is a life-threatening disease. In
      this study, we aimed to evaluate long-term outcomes of the use of 50 mg
      recombinant tissue-type plasminogen activator (rt-PA) in the management of PTE in
      terms of relapse, pulmonary hypertension (PH), mortality and hemorrhage and to
      compare with the use of 100 mg rt-PA. METHODS: The study was designed as a
      retrospective cohort. Patients who were diagnosed as acute PTE and received
      either 50 or 100 mg rt-PA in a tertiary care hospital between 2010 and 2015 were
      included in the study. Rates of relapse, PH, mortality (in-hospital and long
      term) and hemorrhage (major and minor) were calculated for each treatment group.
      RESULTS: A total 117 patients, 73 females and 44 males, were evaluated. Eighty
      three patients were administered 100 mg rt-PA, and 34 were administered 50 mg rt
      PA. The mean age was lower in the 100 mg group compared to the 50 mg group (61 +/
      15 vs 69 +/- 14 years). There was a significant decrease in PH in each group at
      3 months follow-up (P < .001). Although statistically nonsignificant, the relapse
      rate was lower in the 50 mg rt-PA group, but the 5-year mortality rate was higher
      in 50 mg rt-PA group (35.2% vs 27.7%, P = .50). Mortality was associated with
      older age and presence of malignancy. CONCLUSIONS: Our results suggest that both
      doses of rt-PA have similar efficacy. The high mortality rate in the 50 mg group
      may have resulted from patient selection.

PMID- 29044968
TI  - A prospective randomised placebo-controlled study of the impact of
      dutasteride/tamsulosin combination therapy on sexual function domains in sexually
      active men with lower urinary tract symptoms (LUTS) secondary to benign prostatic
      hyperplasia (BPH).
AB  - OBJECTIVE: To prospectively assess the impact of the fixed-dose combination (FDC)
      of the 5alpha-reductase inhibitor (5ARI), dutasteride 0.5 mg and the alpha1 
      adrenoceptor antagonist, tamsulosin 0.4 mg (DUT-TAM FDC) therapy on sexual
      function domain scores in sexually active men with lower urinary tract symptoms
      (LUTS) secondary to benign prostatic hyperplasia (BPH), using the Men's Sexual
      Health Questionnaire (MSHQ). PATIENTS AND METHODS: This European and Australian
      double-blind, placebo-controlled, parallel-group study was conducted at 51
      centres. INCLUSION CRITERIA: age >=50 years, International Prostate Symptom Score
      >=12, prostate volume >=30 cc, prostate-specific antigen 1.5-10 ng/mL. Patients
      were randomised 1:1 to DUT-TAM FDC therapy or placebo for 12 months. The change
      from baseline to Month 12 on the total MSHQ (primary endpoint) and MSHQ erection,
      ejaculation and satisfaction domains (secondary outcome) was assessed, using a
      mixed model repeated measures analysis. Safety was evaluated. RESULTS: The
      intention-to-treat population included 489 patients (243 DUT-TAM FDC therapy; 246
      placebo). A significant decrease (worsening) was observed with DUT-TAM FDC
      therapy versus placebo on the total MSHQ score (-8.7 vs -0.7; standard error
      [se]: 0.81, 0.78; P < 0.001), and the ejaculation (-7.5 vs -0.6; se: 0.56, 0.55;
      P < 0.001) and satisfaction (-0.6 vs +0.3; se: 0.3, 0.29, P = 0.047) domains, but
      not the erection domain (-1.0 vs -0.5; se: 0.19, 0.19, P = 0.091). CONCLUSION:
      This is the first domain-specific quantitative evaluation of DUT-TAM FDC therapy
      on sexual function in men with LUTS secondary to BPH. The observed changes in the
      MSHQ with DUT-TAM FDC therapy were mainly driven by changes in the ejaculation
      domain. These findings will help give context to erectile and ejaculatory
      dysfunction AEs reported spontaneously in earlier 5ARI studies.

PMID- 29044969
TI  - Multichannel Charge Transfer and Mechanistic Insight in Metal Decorated 2D-2D Bi2
      WO6 -TiO2 Cascade with Enhanced Photocatalytic Performance.
AB  - Promising semiconductor-based photocatalysis toward achieving efficient solar-to
      chemical energy conversion is an ideal strategy in response to the growing
      worldwide energy crisis, which however is often practically limited by the
      insufficient photoinduced charge-carrier separation. Here, a rational cascade
      engineering of Au nanoparticles (NPs) decorated 2D/2D Bi2 WO6 -TiO2 (B-T)
      binanosheets to foster the photocatalytic efficiency through the manipulated flow
      of multichannel-enhanced charge-carrier separation and transfer is reported.
      Mechanistic characterizations and control experiments, in combination with
      comparative studies over plasmonic Au/Ag NPs and nonplasmonic Pt NPs decorated
      2D/2D B-T composites, together demonstrate the cooperative synergy effect of
      multiple charge-carrier transfer channels in such binanosheets-based ternary
      composites, including Z-scheme charge transfer, "electron sink," and surface
      plasmon resonance effect, which integratively leads to the boosted photocatalytic
      performance.

PMID- 29044970
TI  - Ethnic disparities in rates of publicly funded bariatric surgery in New Zealand
      (2009-2014).
AB  - BACKGROUND: Publicly funded bariatric surgery in New Zealand (NZ) is steadily on
      the rise to meet the obesity epidemic. Ethnic disparities in obesity rates exist
      in NZ with Maori and Pacific people having three to five times higher rates than
      all other ethnic groups within NZ. Ethnic disparities in rates of bariatric
      surgery have been reported internationally. This research sought to describe
      rates of publically funded bariatric surgery by self-identified ethnicity in NZ.
      METHODS: Using reported census and hospitalization discharge data from Statistics
      NZ and the NZ Ministry of Health, we calculated estimate rates of publicly funded
      bariatric surgery in the morbidly obese population from June 2009 to July 2014.
      RESULTS: The average number of publicly funded bariatric procedures performed per
      1000 morbidly obese patients from June 2009 to July 2014 was 3.0 for European,
      1.4 for Maori and 0.7 for Pacific ethnicities. CONCLUSION: While these data
      should be interpreted cautiously due to data limitations, the estimated rates may
      indicate that bariatric services are currently being provided inequitably across
      the major ethnic groups within NZ. We suggest that further studies should be
      performed to explore potential patient, healthcare provider and system-level
      factors that may contribute to ethnic disparities in the rates of publicly funded
      bariatric surgery in NZ.

PMID- 29044972
TI  - Corrigendum for Ezard and Purvis (2016) DOI: 10.1111/ele.12626.

PMID- 29044971
TI  - Drug nanocrystals for cancer therapy.
AB  - Drug nanocrystals (NCs) with fascinating physicochemical properties have
      attracted great attention in drug delivery. High drug-loading efficiency, great
      structural stability, steady dissolution, and long circulation time are a few
      examples of these properties, which makes drug NCs an excellent formulation for
      efficient cancer therapy. In the last two decades, there are a lot of hydrophobic
      or lipophilic drugs, such as paclitaxel (PTX), camptothecin (CPT), thymectacin,
      busulfan, cyclosporin A, 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide (HPPH),
      and so on, which have been formulated into drug NCs for cancer therapy. In this
      review, we summarized the recent advances in drug NCs-based cancer treatment. So
      far, there are main three methods to synthesize drug NCs, including top-down,
      bottom-up, and combination methods. The characterization methods of drug NCs were
      also elaborated. Furthermore, the applications and mechanisms of drug NCs were
      introduced by their administration routes. At the end, we gave a brief conclusion
      and discussed the future perspectives of drug NCs in cancer therapy. This article
      is categorized under: Implantable Materials and Surgical Technologies >
      Nanomaterials and Implants Therapeutic Approaches and Drug Discovery >
      Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology >
      Nanoscale Systems in Biology.

PMID- 29044973
TI  - Surface water CO2 concentration influences phytoplankton production but not
      community composition across boreal lakes.
AB  - Recent experimental evidence suggests that changes in the partial pressure of CO2
      (pCO2 ), in concert with nutrient fertilisation, may result in increased primary
      production and shifted phytoplankton community composition that favours species
      lacking adaptations to low CO2 environments. It is not clear whether these
      results apply in ambient freshwaters, which are already often supersaturated in
      CO2 , and where phytoplankton structure and activity are under complex control of
      diverse local and regional factors. Here, we use a large-scale comparative study
      of 69 boreal lakes to explore the influence of existing CO2 gradients (c. 50-2300
      MUatm) on phytoplankton community composition and biomass production. While
      community composition did not respond to pCO2 gradients, gross primary production
      was enhanced, but only in lakes already supersaturated in CO2 , demonstrating
      that environmental context is key in determining pCO2 -phytoplankton
      interactions. We further argue that increased atmospheric CO2 is unlikely to
      influence phytoplanktonic composition and production in northern lakes.

PMID- 29044974
TI  - Quality of life related variables measured for three multifocal diffractive
      intraocular lenses: a prospective randomised clinical trial.
AB  - IMPORTANCE: Quality of vision after multifocal intraocular lens (IOLs)
      implantation in relation to patient satisfaction. It is important to include the
      evaluation of visual quality and patient satisfaction in clinical practice.
      BACKGROUND: To evaluate and compare quality of life and patient satisfaction
      after implantation of three types of diffractive-refractive and apodized
      diffractive bifocal and trifocal multifocal IOLs. DESIGN: Comparative,
      prospective, case series and randomized. PARTICIPANTS: Hundred and four eyes of
      52 patients. METHODS: Three multifocal IOLs: AT LISA 809 M (Carl Zeiss Meditec)
      (AT LISA group, 38 eyes), AT LISAtri 839MP (Carl Zeiss Meditec) (AT LISAtri
      group, 32 eyes), and ReSTOR SN6AD1 (Alcon) (ReSTOR group, 34 eyes) were implanted
      after cataract surgery. MAIN OUTCOME MEASURES: Contrast sensitivity, photopic
      phenomena, patient satisfaction and quality of life criteria were evaluated.
      RESULTS: Patient of >= 88% were satisfied with near and intermediate visual
      outcomes. Better distance-corrected intermediate visual acuity at 90 cm was
      detected for AT LISA tri group (P < 0.04). No statistically significant
      differences were found among groups in postoperative contrast sensitivity (P >=
      0.053). There were no significant differences in spectacle dependence scores
      among the groups (P >= 0.180). The addition of an intermediate focus did not
      statistically affect halo and glare size and intensity (P >= 0.256) or subjective
      impact (P >= 0.077). Patient satisfaction was consistently high for all groups (P
      >= 0.154). CONCLUSIONS AND RELEVANCE: Contrast sensitivity outcomes and patient
      satisfaction remained high in the trifocal group when compared to the bifocal IOL
      groups.

PMID- 29044975
TI  - Comparative Proteomic Analysis of Three Xanthomonas spp. Cultured in Minimal and
      Rich Media.
AB  - Bacteria change their gene expression when exposed to different nutrient
      conditions. The levels of proteins do not always correlate with those of RNAs,
      hence proteomic analysis is required for understanding how bacteria adapt to
      different conditions. Herein, differentially abundant proteins from Xanthomonas
      oryzae pv. oryzae (Xoo), X. campestris pv. vesicatoria (Xcv), and X. axonopodis
      pv. glycines (Xag), which were cultured in rich media and in minimal media, were
      determined using label-free shotgun proteomic analysis and clusters of
      orthologous groups classification. The detected proteins from all three species
      ranged from 1190 to 1187. Among them, 702, 584, and 529 proteins from Xoo, Xcv,
      and Xag, respectively, were more (> twofold) abundant depending on the media,
      indicating that about 11.4-13.8% of proteins from the three species were
      differentially expressed. The levels of abundant proteins in minimal media were
      significantly higher than those in rich media for all three species,
      demonstrating how Xanthomonas species actively change their protein expression in
      different nutrient conditions. These results will lead to new insights in
      elucidation of cellular mechanisms involved in virulence and adaption of bacteria
      to harsh environments for further studies. The MS proteomics data have been
      deposited to the ProteomeXchange Consortium with the dataset identifier
      PXD006310.

PMID- 29044976
TI  - Transcoronary pacing to assess myocardial viability prior to percutaneous
      coronary intervention: Pilot study to assess feasibility.
AB  - BACKGROUND: The assessment of myocardial viability is crucial before percutaneous
      coronary intervention (PCI) is carried out to ensure that the patient will gain
      benefit. Trans-coronary pacing (TCP) has previously been used to pace myocardium
      but may also provide information on myocardial viability. METHODS: Patients with
      a single, significant coronary stenosis requiring PCI were recruited. They
      underwent a cardiac MRI to assess myocardial viability. Prior to PCI, a coronary
      guidewire was used to measure pacing threshold, impedance, and R-wave amplitude
      in different myocardial segments to determine any association between the
      electrical parameters and myocardial viability. RESULTS: Eight patients were
      recruited and six patients underwent intervention. Pacing sensitivity did not
      demonstrate statistically significant differences between normal and scarred
      myocardium. Impedance demonstrated a mean of 304.8 +/- 74.0 Omega in normal
      myocardium (NM), 244.1 +/- 66.6 Omega in <50% myocardial scar (MS), and 222.3 +/-
      33.8 Omega in >=50% MS. Pacing threshold demonstrated a mean of 1.960 +/- 1.226 V
      in NM, 5.009 +/- 2.773 V in <50% MS, and 3.950 +/- 0.883 V in >=50% MS. For both
      impedance and threshold, there was a significant difference among the groups (P =
      0.12 and P = 0.002, respectively), and post hoc Tukey's pairwise comparison
      demonstrated significant differences between NM and scarred myocardium. No
      significant differences were found between <50% MS and >=50% MS. CONCLUSIONS:
      Impedance and pacing threshold, measured during TCP, can be used to differentiate
      between normal myocardium and scarred myocardium. Further research is needed to
      determine whether TCP can discriminate between viable and nonviable myocardium.

PMID- 29044977
TI  - Plasmon-Exciton Coupling Interaction for Surface Catalytic Reactions.
AB  - In this review, we firstly reveal the physical principle of plasmon-exciton
      coupling interaction with steady absorption spectroscopy, and ultrafast
      transition absorption spectroscopy, based on the pump-prop technology. Secondly,
      we introduce the fabrication of electro-optical device of two-dimensional
      semiconductor-nanostructure noble metals hybrid, based on the plasmon-exciton
      coupling interactions. Thirdly, we introduce the applications of plasmon-exciton
      coupling interaction in the field of surface catalytic reactions. Lastly, the
      perspective of plasmon-exciton coupling interaction and applications closed this
      review.

PMID- 29044978
TI  - Early postoperative fever in paediatric patients undergoing cochlear implant
      surgery.

PMID- 29044979
TI  - Real-world visual outcomes in patients with neovascular age-related macular
      degeneration receiving aflibercept at fixed intervals as per UK licence.
AB  - IMPORTANCE: To assess the impact of injection frequency on visual outcomes in
      patients with neovascular age-related macular degeneration (nAMD) treated with
      intravitreal aflibercept. BACKGROUND: The UK licence for treatment of nAMD with
      aflibercept is based on the VIEW protocol. We tested the hypothesis that patients
      receiving fewer than the eight recommended injections in the first year would
      experience worse visual outcomes. DESIGN: Retrospective, single-centre
      observational study. PARTICIPANTS: There were 42 eyes from 42 patients included.
      METHODS: Fight Retinal Blindness! software was used to record real-world outcomes
      of all treatment-naive eyes receiving aflibercept for at least 1 year. MAIN
      OUTCOME MEASURES: Visual acuity (VA) at 1 year in eyes which received the
      recommended eight injections versus those receiving seven or fewer injections.
      RESULTS: There were 21 eyes (50%) that received the recommended eight aflibercept
      injections in the first year of treatment, whilst 14 eyes received seven
      injections, five received six injections and two received only five injections,
      with median VA change +7.0, +5.0, -4.0 and -6.5 LogMAR letters, respectively.
      Those eyes receiving seven or fewer injections had worse baseline vision. The
      main reasons for patients being undertreated were insufficient clinic capacity
      and non-attendance due to illness. CONCLUSIONS AND RELEVANCE: Patients in the
      real-world receiving aflibercept for nAMD at fixed intervals as per UK licence
      could achieve similar visual improvement at 1 year compared with phase III
      clinical trials. Undertreated patients had worse visual outcomes. Measures need
      to be introduced to increase clinic capacity and closely follow non-attenders to
      improve future outcomes.

PMID- 29044980
TI  - Phenotypic and genotypic profile of clinical and animal multidrug-resistant
      Salmonella enterica isolates from Mexico.
AB  - AIMS: The objective of this study was to obtain a phenotypic and genotypic
      profile of Salmonella enterica including multidrug-resistant (MDR) isolates from
      food-producing animals and clinical isolates, as well as their genetic
      relatedness in two different States of Mexico (Jalisco and State of Mexico).
      METHODS AND RESULTS: A total of 243 isolates were evaluated in terms of
      antimicrobial resistance (AMR) and related genes through a disk diffusion method
      and PCR respectively; we found 16 MDR isolates, all of them harbouring the blaCMY
      gene but not qnr genes, these isolates represent less than 10% of the collection.
      The pulsed-field gel electrophoresis revealed a higher genotypic similitude
      within isolates of State of Mexico than Jalisco. CONCLUSIONS: A low percentage of
      Salmonella isolates were resistant to relevant antibiotics in human health,
      nevertheless, the AMR and involved genes were similar despite the different
      serovars and origin of the isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      investigation provided an insight of the current status of AMR of Salmonella
      isolates in two States of Mexico and pinpoint the genes involved in AMR and their
      epidemiological relationship, the information could help to determine an adequate
      therapy in human and veterinary medicine.

PMID- 29044981
TI  - Use of biocontrol agents and botanicals in integrated management of Botrytis
      cinerea in table grape vineyards.
AB  - BACKGROUND: There is increasing interest in the use of biological control agents
      (BCAs) and botanicals (BOTs) due to increasing awareness of the environmental and
      human health risks associated with synthetic plant protection products. The BCAs
      Bacillus subtilis strain QST713, Bacillus amyloliquefaciens strain D747 and
      Aureobasidium pullulans strains DSM14940 and DSM14941, and the BOTs Melaleuca
      alternifolia and terpenic extracts are proposed for the control of grey mould in
      vineyards. This study was aimed at evaluating their effectiveness in integrated
      crop management strategies and their outcomes in terms of the management of
      fungicide resistance and residues. RESULTS: In field trials carried out on table
      grapes in southern Italy, use of BCAs or BOTs alternately or mixtures of BCAs or
      BOTs with the succinate dehydrogenase inhibitor fungicide fluopyram showed
      efficacy of up to 96% against grey mould on bunches, comparable with the chemical
      reference strategy (up to 87%). By contrast, use of BCAs or BOTs (up to 11
      sprays) alone was not effective (< 30%) under high disease pressure. The
      integrated use of BCAs or BOTs reduced the spread of succinate dehydrogenase
      inhibitor-resistant conidia, as well as fungicide residues in grapes.
      CONCLUSIONS: Spray schedules based on integration of BCAs or BOTs with fungicides
      are effective against grey mould and reduce the risk of fungicide resistance in
      B. cinerea and fungicide residues in grapes. (c) 2017 Society of Chemical
      Industry.

PMID- 29044982
TI  - Surface-Assisted Self-Assembly Strategies Leading to Supramolecular Hydrogels.
AB  - Localized molecular self-assembly processes leading to the growth of
      nanostructures exclusively from the surface of a material is one of the great
      challenges in surface chemistry. In the last decade, several works have been
      reported on the ability of modified or unmodified surfaces to manage the self
      assembly of low-molecular-weight hydrogelators (LMWH) resulting in localized
      supramolecular hydrogel coatings mainly based on nanofiber architectures. This
      Minireview highlights all strategies that have emerged recently to initiate and
      localize LMWH supramolecular hydrogel formation, their related fundamental issues
      and applications.

PMID- 29044983
TI  - Horseradish Peroxidase Catalyzed Hydrogelation for Biomedical, Biopharmaceutical,
      and Biofabrication Applications.
AB  - Horseradish peroxidase (HRP)-catalyzed hydrogelation has attracted much attention
      owing to the ease of handling, high biocompatibility, and processability. This
      review summarizes recent developments, including cutting-edge research into the
      use of HRP-mediated hydrogelation toward biomedical, biopharmaceutical, and
      biofabrication applications. From the viewpoint of polymer chemistry, the basic
      chemistry behind hydrogelation, the structure-property relationship, and
      hybridization of multiple materials by using HRP-catalyzed hydrogelation are
      summarized. From the chemical engineering perspective, strategies for controlling
      hydrogelation kinetics, hydrogel characteristics, and hydrogelation processes are
      summarized and discussed in detail. Strategies for obtaining biomaterials for
      medical and pharmaceutical use, and biofabrication for tissue engineering and
      regenerative medicine emerge by unifying the aspects of HRP-mediated
      hydrogelation.

PMID- 29044985
TI  - Beneficial effect of recombinant rC1rC2 collagenases on human islet function:
      Efficacy of low-dose enzymes on pancreas digestion and yield.
AB  - A high number of human islets can be isolated by using modern purified tissue
      dissociation enzymes; however, this requires the use of >20 Wunsch units (WU)/g
      of pancreas for digestion. Attempts to reduce this dose have resulted in pancreas
      underdigestion and poor islet recovery but improved islet function. In this
      study, we achieved a high number of functional islets using a low dose of
      recombinant collagenase enzyme mixture (RCEM-1200 WU rC2 and 10 million collagen
      degrading activity [CDA] U of rC1 containing about 209 mg of collagenase to
      digest a 100-g pancreas). The collagenase dose used in these isolations is about
      42% of the natural collagenase enzyme mixture (NCEM) dose commonly used to digest
      a 100-g pancreas. Low-dose RCEM was efficient in digesting entire pancreases to
      obtain higher yield (5535 +/- 830 and 2582 +/- 925 islet equivalent/g, P < .05)
      and less undigested tissue (16.7 +/- 5% and 37.8 +/- 3%, P < .05) compared with
      low-dose NCEM (12WU/g). Additionally, low-dose RCEM islets retained better
      morphology (confirmed with scanning electron microscopy) and higher in vitro
      basal insulin release (2391 +/- 1342 and 1778 +/- 978 MUU/mL; P < .05) compared
      with standard-dose NCEM. Nude mouse bioassay demonstrated better islet function
      for low-dose RCEM (area under the curve [AUC] 24 968) compared with low-dose (AUC
      38 225) or standard-dose NCEM (AUC-38 685), P < .05. This is the first report
      indicating that islet function can be improved by using low-dose rC1rC2 (RCEM).

PMID- 29044984
TI  - Three dimensional printed calcium phosphate and poly(caprolactone) composites
      with improved mechanical properties and preserved microstructure.
AB  - Biphasic calcium phosphate scaffolds formed via three dimensional (3D) printing
      technology to exhibit porosity and chemical resorbability to promote
      osseointegration often lack the strength and toughness required to withstand
      loading in bone tissue engineering applications. Herein, sintering and
      CaP:poly(caprolactone) (PCL) composite formation were explored to improve 3D
      printed scaffold strength and toughness. Hydroxyapatite and alpha-tricalcium
      phosphate (alpha-TCP) biphasic calcium powders were printed using phosphoric acid
      binder, which generated monetite and hydroxyapatite scaffolds. Upon sintering,
      evolution of beta-TCP was observed along with an increase in flexural strength
      and modulus but no effect on fracture toughness was observed. Furthermore,
      scaffold porosity increased with sintering. Additionally, two techniques of PCL
      composite formation were employed: postprint precipitation and 3D print
      codeposition to further augment scaffold mechanical properties. While both
      techniques significantly improved flexural strength, flexural modulus, and
      fracture toughness under most conditions explored, precipitation yielded more
      substantial increases in these properties, which is attributed to better
      continuity of the PCL phase. However, precipitation also compromised surface
      porosity due to PCL passivation of the calcium phosphate surface, which may
      subsequently hinder scaffold integration and bone regeneration. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 663-672, 2018.

PMID- 29044986
TI  - Spectroscopic investigation of the anticancer alkaloid piperlongumine binding to
      human serum albumin from the viewpoint of drug delivery.
AB  - Piperlongumine (PL) is a very promising natural agent with a high potential for
      cancer treatment. To overcome the poor water solubility of PL, there is a need to
      develop a novel water-soluble formulation in which PL is non-covalently bound to
      human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic
      techniques under simulated physiological conditions. Spectroscopic evidence
      showed that the interaction of PL with HSA could form a PL-HSA complex. The
      binding constant (Ka ) values increased with increasing temperature, and a
      similar dependence was observed for the number of binding sites (n) values. The
      number of PL molecules bound to HSA reached 8.1 when the temperature was raised
      to 308 K. Thermodynamic calculation results suggested that the binding reaction
      occurred spontaneously but was an entropy-driven process, and hydrophobic forces
      played a major role in stabilizing the complex. Furthermore, PL binding induced
      conformational and microenvironmental changes in HSA. Displacement studies
      indicated that PL and warfarin had separate binding regions in site I. Therefore,
      it would be possible to develop a novel water-soluble formulation involving PL
      and HSA. This study may provide some valuable information in terms of improving
      the poor water solubility of PL.

PMID- 29044987
TI  - Sticky fingers at work: Palmitoylation-dependent MC1R activation.

PMID- 29044989
TI  - Intercalating Ti2 Nb14 O39 Anode Materials for Fast-Charging, High-Capacity and
      Safe Lithium-Ion Batteries.
AB  - Ti-Nb-O binary oxide materials represent a family of promising intercalating
      anode materials for lithium-ion batteries. In additional to their excellent
      capacities (388-402 mAh g-1 ), these materials show excellent safety
      characteristics, such as an operating potential above the lithium plating voltage
      and minimal volume change. Herein, this study reports a new member in the Ti-Nb-O
      family, Ti2 Nb14 O39 , as an advanced anode material. Ti2 Nb14 O39 porous spheres
      (Ti2 Nb14 O39 -S) exhibit a defective shear ReO3 crystal structure with a large
      unit cell volume and a large amount of cation vacancies (0.85% vs all cation
      sites). These morphological and structural characteristics allow for short
      electron/Li+ -ion transport length and fast Li+ -ion diffusivity. Consequently,
      the Ti2 Nb14 O39 -S material delivers significant pseudocapacitive behavior and
      excellent electrochemical performances, including high reversible capacity (326
      mAh g-1 at 0.1 C), high first-cycle Coulombic efficiency (87.5%), safe working
      potential (1.67 V vs Li/Li+ ), outstanding rate capability (223 mAh g-1 at 40 C)
      and durable cycling stability (only 0.032% capacity loss per cycle over 200
      cycles at 10 C). These impressive results clearly demonstrate that Ti2 Nb14 O39 
      S can be a promising anode material for fast-charging, high capacity, safe and
      stable lithium-ion batteries.

PMID- 29044988
TI  - Age-associated microRNA expression in human peripheral blood is associated with
      all-cause mortality and age-related traits.
AB  - Recent studies provide evidence of correlations of DNA methylation and expression
      of protein-coding genes with human aging. The relations of microRNA expression
      with age and age-related clinical outcomes have not been characterized
      thoroughly. We explored associations of age with whole-blood microRNA expression
      in 5221 adults and identified 127 microRNAs that were differentially expressed by
      age at P < 3.3 * 10-4 (Bonferroni-corrected). Most microRNAs were underexpressed
      in older individuals. Integrative analysis of microRNA and mRNA expression
      revealed changes in age-associated mRNA expression possibly driven by age
      associated microRNAs in pathways that involve RNA processing, translation, and
      immune function. We fitted a linear model to predict 'microRNA age' that
      incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly
      with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2),
      suggesting that microRNA age may complement mRNA and epigenetic age prediction
      models. We used the difference between microRNA age and chronological age as a
      biomarker of accelerated aging (Deltaage) and found that Deltaage was associated
      with all-cause mortality (hazards ratio 1.1 per year difference, P = 4.2 * 10-5
      adjusted for sex and chronological age). Additionally, Deltaage was associated
      with coronary heart disease, hypertension, blood pressure, and glucose levels. In
      conclusion, we constructed a microRNA age prediction model based on whole-blood
      microRNA expression profiling. Age-associated microRNAs and their targets have
      potential utility to detect accelerated aging and to predict risks for age
      related diseases.

PMID- 29044990
TI  - Transcriptome analysis for UVB-induced phototoxicity in mouse retina.
AB  - Throughout life, the human eye is continuously exposed to sunlight and artificial
      lighting. Ambient light exposure can lead to visual impairment and transient or
      permanent blindness. To mimic benign light stress conditions, Mus musculus eyes
      were exposed to low-energy UVB radiation, ensuring no severe morphological
      changes in the retinal structure post-exposure. We performed RNA-seq analysis to
      reveal the early transcriptional changes and key molecular pathways involved
      before the activation of the canonical cell death pathway. RNA-seq analysis
      identified 537 genes that were differentially modulated, out of which 126 were
      clearly up regulated (>2-fold, P < .01) and 51 were significantly down regulated
      (<2-fold, P < .01) in response to UVB irradiation in the mouse retina. Gene
      ontology analysis revealed that UVB exposure affected pathways for cellular
      stress and signaling (eg, Creb3, Ddrgk1, Grin1, Map7, Uqcc2, Uqcrb), regulation
      of chromatin and gene expression (eg, Chd5, Jarid2, Kat6a, Smarcc2, Sumo1,
      Zfp84), transcription factors (eg, Asxl2, Atf7, Per1, Phox2a, Rxra), RNA
      processing, and neuronal genes (eg, B4gal2, Drd1, Grm5, Rnf40, Rnps1, Usp39,
      Wbp4). The differentially expressed genes from the RNA-seq analysis were
      validated by quantitative PCR. Both analyses yielded similar gene expression
      patterns. The genes and pathways identified here improve the understanding of
      early transcriptional responses to UVB irradiation. They may also help in
      elucidating the genes responsible for the inherent susceptibility of humans to
      UVB-induced retinal diseases.

PMID- 29044992
TI  - Use of thrombolytic therapy in DCD liver transplantation does not seem to improve
      outcome.

PMID- 29044991
TI  - Tuneable Transient Thermogels Mediated by a pH- and Redox-Regulated
      Supramolecular Polymerization.
AB  - A multistimuli-responsive transient supramolecular polymerization of beta-sheet
      encoded dendritic peptide monomers in water is presented. The amphiphiles, which
      contain glutamic acid and methionine, undergo a glucose oxidase catalyzed,
      glucose-fueled transient hydrogelation in response to an interplay of pH and
      oxidation stimuli, promoted by the production of reactive oxygen species (ROS).
      Adjusting the enzyme and glucose concentration allows tuning of the assembly and
      the disassembly rates of the supramolecular polymers, which dictate the stiffness
      and transient stability of the hydrogels. The incorporation of triethylene glycol
      chains introduces thermoresponsive properties to the materials. We further show
      that repair enzymes are able to reverse the oxidative damage in the methionine
      based thioether side chains. Since ROS play an important role in signal
      transduction cascades, our strategy offers great potential for applications of
      these dynamic biomaterials in redox microenvironments.

PMID- 29044993
TI  - Intra-articular hyaluronic acid injection in treating knee osteoarthritis:
      assessing risk of bias in systematic reviews with ROBIS tool.
AB  - OBJECTIVES: Intra-articular injection of hyaluronic acid (HA) is a common, yet
      controversial therapeutic option in treating knee osteoarthritis (OA). The
      purpose of the present study was to assess the risk of bias (RoB) of systematic
      reviews (SRs) and to summarize available evidence of HA in treating knee OA.
      METHODS: A systematic search of SRs published through to December 2016 was
      conducted using the MEDLINE, EMBASE and Cochrane Library. The RoB of included SRs
      was assessed by ROBIS tool. In addition, the methodological quality of primary
      studies in SRs with low RoB was evaluated according to the Cochrane Handbook. The
      evidence quality of each primary outcome of SRs with low RoB was determined by
      the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation)
      system. RESULTS: Thirty-one SRs were eligible for inclusion. According to the
      ROBIS tool, there were 13 SRs with low RoB, 16 with high RoB and two with unclear
      RoB. The methodological quality of a total of 135 primary studies was evaluated
      and summarized. Forty-two outcomes from these 13 SRs were classified into the
      four following quality levels based on the GRADE approach: three outcomes with
      high quality, eight with moderate quality, 12 with low quality and 19 with very
      low quality. CONCLUSIONS: This study evaluated RoB in SRs for managing knee OA
      with HA and assessed the evidence quality of each primary outcome in SRs with low
      RoB. These results can help users of SRs to improve the process of SR assessment
      in developing overviews or guidelines, leading to more reliable recommendations
      for improvements in treating knee OA. Registration: PROSPERO
      ((http://www.crd.york.ac.uk/PROSPERO) [CRD42017057384].

PMID- 29044994
TI  - Characterization and expression pattern of r-spondin1 in Cynoglossus semilaevis.
AB  - r-spondin1 (rspo1) encodes a secreted protein that is involved in the
      determination and differentiation of the mammalian ovary. However, little
      information is yet available for teleosts. Here, we identified a homologue of
      rspo1 in Cynoglossus semilaevis. The full-length cDNA of rspo1 had a length of
      2,703 bp with an open reading frame of 834 bp, encoding a protein with a length
      of 277 amino-acids. rspo1 expression was detected via qRT-PCR in various tissues,
      and significant sexually dimorphic expression was observed in the gonads.
      Furthermore, ISH located rspo1 in germ cells such as spermatogonia,
      spermatocytes, spermatids, spermatozoa, and oocytes, as well as in somatic cells
      of the gonads. Following knockdown of rspo1 in an ovarian cell line, the
      expressions of wnt4a, beta-catenin, foxl2, and StAR were highly affected; wnt4a
      and beta-catenin were significantly downregulated, whereas foxl2 and StAR were
      significantly upregulated. In summary, these data suggest that rspo1 may be
      involved in the regulation of ovarian development and differentiation through a
      conserved pathway, while the function of the gene in the testis remains elusive.

PMID- 29044995
TI  - miR-200c regulates endothelin-1 induced PASMCs abnormal proliferation and
      apoptosis.
AB  - miR-200c is an antioncogene in multiple tumors. However, its function in the
      pathogenesis of pulmonary arterial hypertension (PAH) has not been thoroughly
      investigated nor understood. In this study, we discovered that miR-200c was able
      to substantially upregulate in pulmonary arterial smooth muscle cells (PASMCs)
      treated with endothelin-1 (ET-1). miR-200c also induced cell proliferation and
      suppressed cell apoptosis in PASMCs in vitro. However, miR-200c had no effect on
      G1/S/G2 transitions during the cell cycle. Furthermore, we identified miR-200c as
      a new regulator of the microtubule associated protein 2 (MAP-2) and zinc finger E
      box binding homeobox1 (ZEB-1) in PASMCs. miR-200c inhibited MAP-2 and ZEB-1
      expression by directly binding to their 3'-untranslated regions(3'UTR) according
      to luciferase assay results. Our findings provide novel insights into the
      mechanisms of PAH pathogenesis and potential molecular biomarkers for PAH
      diagnosis and treatment. (c) 2017 IUBMB Life, 69(11):877-886, 2017.

PMID- 29044996
TI  - Lifestyle, habitat and farmers' risk of exposure to tick bites in an endemic area
      of tick-borne diseases in Hungary.
AB  - Controlling tick bites on farmers is important to the management of tick-borne
      diseases and occupational health risks in agriculture. Based on an extensive
      household survey conducted between June and August 2015 with 219 farmers from
      western Hungary where tick-borne diseases are endemic, we analysed the pattern of
      farmers' self-reported contacts with ticks and investigated the potential
      interactions between farmers, landscape and the risk of exposure to tick bites.
      We developed a lifestyle typology based on farmers' socioeconomic profiles,
      farming objectives and time use patterns, and a habitat typology describing
      different configurations of tick habitats and agricultural areas in place of
      farming. We found no relationship between tick exposure risk and self-prevention.
      The lifestyle typology could be used to classify the risk of tick bites and the
      adoption of prevention measures into different levels, the difference between
      which could further be modified by the habitat typology. Our results suggest that
      (i) farmers who are frequently engaged in outdoor recreations and (ii) part-time
      and inexperienced farmers who have lower rate of preventive actions are likely to
      experience greater exposure to tick bites either in less cultivated, semi-natural
      habitats or in agricultural landscape with highly diverse land uses. Future
      disease prevention practices should take into consideration the interaction of
      lifestyle and habitat and the need to associate different farmer groups with
      different landscape configurations.

PMID- 29044997
TI  - Visual outcomes following vitrectomy for diabetic retinopathy amongst Indigenous
      and non-Indigenous Australians in South Australia and the Northern Territory.
AB  - IMPORTANCE: Visual outcomes following diabetic vitrectomy have not previously
      been studied in an Australian population. BACKGROUND: This analysis aimed to
      determine the rate of, and factors associated with visual success following
      diabetic vitrectomy performed for Indigenous and non-Indigenous Australians, and
      investigate factors predisposing to early progression to diabetic retinopathy
      (DR) requiring vitrectomy. DESIGN: Retrospective, population-based audit.
      PARTICIPANTS: All patients undergoing vitrectomy for the complications of DR in
      South Australia (SA) and the Northern Territory (NT) between 2007 and 2011.
      METHODS: Medical records were audited and data collected, including demographics,
      diabetic history, past treatment for DR, indication for vitrectomy and visual
      acuity pre and postoperatively. MAIN OUTCOME MEASURES: Visual success (gain of
      >=15 ETDRS letters) at 6 and 12 months, postoperatively. RESULTS: A total of 495
      diabetic vitrectomies, for 404 eyes of 335 patients were performed in SA and NT
      between 2007 and 2011. 77 (23%) patients requiring diabetic vitrectomy were
      Indigenous Australians. 87% of patients undergoing diabetic vitrectomy had stable
      or improved vision at 1 year, postoperatively. There was no significant
      difference between indigenous and non-indigenous eyes achieving visual success (P
      = 0.929). Timely preoperative laser treatment (P = 0.03) and preoperative visual
      acuity (P = 0.01) were the predominant factors associated with visual success.
      CONCLUSIONS AND RELEVANCE: Indigenous patients are just as likely to have
      improved vision following diabetic vitrectomy as non-Indigenous Australians.
      However, the small subset of indigenous patients with blind eyes prior to
      vitrectomy are significantly less likely to improve from surgery. The underlying
      factors associated with poor outcomes in this group requires further exploration.

PMID- 29044998
TI  - Liquid chromatographic resolution of proline and pipecolic acid derivatives on
      chiral stationary phases based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic
      acid.
AB  - Two liquid chromatographic chiral stationary phases based on (+)-(18-crown-6)
      2,3,11,12-tetracarboxylic acid were applied to the resolution of the amide
      derivatives of cyclic alpha-amino acids including proline and pipecolic acid.
      Among the five amide derivatives of proline, aniline amide was resolved best on
      the first chiral stationary phase, which contains two N-H tethering amide groups,
      with the separation factor of 1.31 and the resolution of 2.60, and on the second
      chiral stationary phase, which contains two N-CH3 tethering amide groups, with
      the separation factor of 1.57 and the resolution of 5.50. Among the five amide
      derivatives of pipecolic acid, 2-naphthyl amide was resolved best on the first
      chiral stationary phase with the separation factor of 1.30 and the resolution of
      1.75, but 1-naphthylmethyl amide was resolved best on the second chiral
      stationary phase with the separation factor of 1.30 and the resolution of 2.26.
      In general, the second chiral stationary phase was found to be better than the
      first chiral stationary phase in the resolution of the amide derivatives of
      cyclic alpha-amino acids. In this study, the second chiral stationary phase was
      first demonstrated to be useful for the resolution of secondary amino compounds.

PMID- 29045000
TI  - Characterization of the soybean GmALMT family genes and the function of GmALMT5
      in response to phosphate starvation.
AB  - A potential mechanism to enhance utilization of sparingly soluble forms of
      phosphorus (P) is the root secretion of malate, which is mainly mediated by the
      ALMT gene family in plants. In this study, a total of 34 GmALMT genes were
      identified in the soybean genome. Expression patterns diverged considerably among
      GmALMTs in response to phosphate (Pi) starvation in leaves, roots and flowers,
      with expression altered by P availability in 26 of the 34 GmALMTs. One root
      specific GmALMT whose expression was significantly enhanced by Pi-starvation,
      GmALMT5, was studied in more detail to determine its possible role in soybean P
      nutrition. Analysis of GmALMT5 tissue expression patterns, subcellular
      localization, and malate exudation from transgenic soybean hairy roots
      overexpressing GmALMT5, demonstrated that GmALMT5 is a plasma membrane protein
      that mediates malate efflux from roots. Furthermore, both growth and P content of
      transgenic Arabidopsis overexpressing GmALMT5 were significantly increased when
      sparingly soluble Ca-P was used as the external P source. Taken together, these
      results indicate that members of the soybean GmALMT gene family exhibit diverse
      responses to Pi starvation. One member of this family, GmALMT5, might contribute
      to soybean P efficiency by enhancing utilization of sparingly soluble P sources
      under P limited conditions.

PMID- 29044999
TI  - Macrophage subpopulations and their impact on chronic allograft rejection versus
      graft acceptance in a mouse heart transplant model.
AB  - Macrophages infiltrating the allografts are heterogeneous, consisting of
      proinflammatory (M1 cells) as well as antiinflammatory and fibrogenic phenotypes
      (M2 cells); they affect transplantation outcomes via diverse mechanisms. Here we
      found that macrophage polarization into M1 and M2 subsets was critically
      dependent on tumor necrosis factor receptor-associated factor 6 (TRAF6) and
      mammalian target of rapamycin (mTOR), respectively. In a heart transplant model
      we showed that macrophage-specific deletion of TRAF6 (LysMCre Traf6 fl/fl ) or
      mTOR (LysMCre Mtorfl/fl ) did not affect acute allograft rejection. However,
      treatment of LysMCre Mtorfl/fl recipients with CTLA4-Ig induced long-term
      allograft survival (>100 days) without histological signs of chronic rejection,
      whereas the similarly treated LysMCre Traf6 fl/fl recipients developed severe
      transplant vasculopathy (chronic rejection). The presentation of chronic
      rejection in CTLA4-Ig-treated LysMCre Traf6 fl/fl mice was similar to that of
      CTLA4-Ig-treated wild-type B6 recipients. Mechanistically, we found that the
      graft-infiltrating macrophages in LysMCre Mtorfl/fl recipients expressed high
      levels of PD-L1, and that PD-L1 blockade readily induced rejection of otherwise
      survival grafts in the LysMCre Mtorfl/fl recipients. Our findings demonstrate
      that targeting mTOR-dependent M2 cells is critical for preventing chronic
      allograft rejection, and that graft survival under such conditions is dependent
      on the PD-1/PD-L1 coinhibitory pathway.

PMID- 29045001
TI  - Anti-inflammaging effects of human alpha-1 antitrypsin.
AB  - Inflammaging plays an important role in most age-related diseases. However, the
      mechanism of inflammaging is largely unknown, and therapeutic control of
      inflammaging is challenging. Human alpha-1 antitrypsin (hAAT) has immune
      regulatory, anti-inflammatory, and cytoprotective properties as demonstrated in
      several disease models including type 1 diabetes, arthritis, lupus, osteoporosis,
      and stroke. To test the potential anti-inflammaging effect of hAAT, we generated
      transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT
      expressing lines was significantly longer than that of genetically matched
      controls. To understand the mechanism underlying the anti-aging effect of hAAT,
      we monitored the expression of aging-associated genes and found that aging
      induced expressions of Relish (NF-KB orthologue) and Diptericin were
      significantly lower in hAAT lines than in control lines. RNA-seq analysis
      revealed that innate immunity genes regulated by NF-kB were significantly and
      specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti
      inflammaging effect in human cells, we treated X-ray-induced senescence cells
      with hAAT and showed that hAAT treatment significantly decreased the expression
      and maturation of IL-6 and IL-8, two major factors of senescence-associated
      secretory phenotype. Consistent with results from Drosophila,RNA-seq analysis
      also showed that hAAT treatment significantly inhibited inflammation related
      genes and pathways. Together, our results demonstrated that hAAT significantly
      inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA
      approved drug with a confirmed safety profile, this novel therapeutic potential
      may make hAAT a promising candidate to combat aging and aging-related diseases.

PMID- 29045003
TI  - Barbed expansion sphincter pharyngoplasty for the treatment of oropharyngeal
      collapse in obstructive sleep apnoea syndrome: A retrospective study on 17
      patients.

PMID- 29045002
TI  - Association of Vitamin K Status Combined With Vitamin D Status and Lower
      Extremity Function: A Prospective Analysis of Two Knee Osteoarthritis Cohorts.
AB  - OBJECTIVE: Vitamins K and D are important for the function of vitamin K-dependent
      proteins in joint tissues. It is unclear whether these nutrients are mutually
      important to functional outcomes related to knee osteoarthritis (OA). We
      evaluated the association of vitamin K and D sufficiency with lower-extremity
      function in the Health, Aging and Body Composition knee OA substudy (Health ABC)
      and conducted a replication analysis in an independent cohort, the Osteoarthritis
      Initiative (OAI). METHODS: In Health ABC (60% female, mean +/- SD age 75 +/- 3
      years) baseline nutrient status was measured using circulating vitamin K and 25
      hydroxyvitamin D (25[OH]D). Lower-extremity function was assessed using the Short
      Physical Performance Battery (SPPB) and usual 20-meter gait speed. In the OAI
      (58% female, mean +/- SD age 61 +/- 9 years), baseline nutrient intake was
      estimated by food frequency questionnaire. Lower-extremity function was assessed
      using usual 20-meter gait speed and chair stand completion time. Multivariate
      mixed models were used to evaluate the association of vitamin K and D status and
      intake with lower-extremity function over 4-5 years. RESULTS: Health ABC
      participants with sufficient plasma vitamin K (>=1.0 nmoles/liter) and serum
      25(OH)D (>=50 nmoles/liter) generally had better SPPB scores and faster usual
      gait speed over followup (P <= 0.002). In the OAI, sufficient vitamin K and
      vitamin D intake combined was associated with overall faster usual gait speed and
      chair stand completion time over followup (P <= 0.029). CONCLUSION: Sufficient
      vitamin K status combined with sufficient vitamin D status was associated with
      better lower-extremity function in 2 knee OA cohorts. These findings merit
      confirmation in vitamin K and D co-supplementation trials.

PMID- 29045004
TI  - Wound care evidence, knowledge and education amongst nurses: a semi-systematic
      literature review.
AB  - The aims of this study were to determine the knowledge and skills of nurses
      involved in wound care, to provide a critical overview of the current evidence
      base underpinning wound care and to determine the extent of utilisation of
      existing evidence by nurses involved in the management of wounds in practice. A
      semi-systematic review of the literature was undertaken on Cinahl, Medline
      Science Direct and Cochrane using the search terms: wound, tissue viability,
      education, nurse, with limitations set for dates between 2009 and 2017 and
      English language. Shortfalls were found in the evidence base underpinning wound
      care and in links between evidence and practice, prevalence of ritualistic
      practice and in structured education at pre- and post-registration levels. The
      evidence underpinning wound care practice should be further developed, including
      the conduction of independent studies and research of qualitative design to
      obtain rich data on both patient and clinician experiences of all aspects of
      wound management. More structured wound care education programmes, both at pre
      registration/undergraduate and professional development levels, should be
      established.

PMID- 29045005
TI  - Natural antibodies to oxidation-specific epitopes: innate immune response and
      venous thromboembolic disease.
AB  - : Essentials Natural antibodies to oxidation-specific epitopes have
      antithrombotic properties. We evaluated the relation between natural IgM and IgG
      antibodies and the venous thrombosis risk. Risk of recurrent thrombosis was
      higher in patients with low natural IgM antibody levels. The protective effect of
      high IgM levels suggests a role of innate immune response in thrombosis. SUMMARY:
      Background and objectives Natural antibodies to oxidation-specific epitopes
      protect from atherothrombotic events. Whether mechanisms of innate immunity are
      relevant in the pathogenesis of venous thromboembolism (VTE) is unknown.
      Patients/Methods We measured plasma levels of immunoglobulin M (IgM) antibodies
      to oxidized low-density lipoproteins (OxLDL) and phosphocholine (PC) by enzyme
      linked immune assay in 663 patients with unprovoked VTE, who were prospectively
      followed after discontinuation of anticoagulation for a median of 8.8 years. The
      study endpoint was recurrent VTE. Results IgM antibody levels to OxLDL and PC
      were higher in patients without compared to those with recurrent VTE (n = 174,
      26.2%). For each doubling of OxLDL-IgM or PC-IgM the hazard ratio (HR) of
      recurrence was 0.88 (95% confidence interval [CI], 0.77-1.01) and 0.82 (95% CI,
      0.71-0.94), respectively. After 5 years the probability of recurrence in patients
      with PC-IgM levels in the highest tertile (> 19.6 RLU/100 ms) was 13.0% (95% CI,
      8.1-17.6%), compared with 21.1% (95% CI, 14.9-26.9%) in the middle tertile and
      20.6% (95% CI, 14.7-26.0%) in the lowest tertile. The corresponding HR was 0.56
      (0.39-0.82) for PC-IgM levels in the highest compared with the lowest tertile.
      Neither immunoglobulin G IgG antibody levels to OxLDL nor those to PC were
      associated with risk of VTE. Conclusion Levels of natural IgM antibodies to
      oxidation-specific epitopes are inversely related to the risk of VTE.

PMID- 29045006
TI  - Identification of Proteins Interacting with Ubiquitin Chains.
AB  - Ubiquitylation, the modification of proteins with ubiquitin (Ub), is one of the
      most versatile post-translational modifications in eukaryotic cells. Since Ub
      also serves as its own substrate, proteins can be modified by numerous different
      Ub chains, in which the individual moieties are linked via one or several of the
      seven lysines of Ub. Homogeneous Ub chains, in which the moieties are
      sequentially linked via the same residue, have been most extensively studied.
      However, due to their restricted availability, the functions of Ub chains linked
      via K27, K29, or K33 are poorly understood. We have developed an approach that,
      for the first time, allows the generation of all seven homogeneous Ub chains in
      large quantities. The potential of our approach is demonstrated by the
      identification of previously unknown interaction partners of K27-, K29-, and K33
      linked Ub chains by affinity-based proteomics.

PMID- 29045007
TI  - Chromatin-remodeling factor OsINO80 is involved in regulation of gibberellin
      biosynthesis and is crucial for rice plant growth and development.
AB  - The phytohormone gibberellin (GA) plays essential roles in plant growth and
      development. Here, we report that OsINO80, a conserved ATP-dependent chromatin
      remodeling factor in rice (Oryza sativa), functions in both GA biosynthesis and
      diverse biological processes. OsINO80-knockdown mutants, derived from either T
      DNA insertion or RNA interference, display typical GA-deficient phenotypes,
      including dwarfism, reduced cell length, late flowering, retarded seed
      germination and impaired reproductive development. Consistently, transcriptome
      analyses reveal that OsINO80 knockdown results in downregulation by more than two
      fold of over 1,000 genes, including the GA biosynthesis genes CPS1 and GA3ox2,
      and the dwarf phenotype of OsINO80-knockdown mutants can be rescued by the
      application of exogenous GA3. Chromatin immunoprecipitation (ChIP) experiments
      show that OsINO80 directly binds to the chromatin of CPS1 and GA3ox2 loci.
      Biochemical assays establish that OsINO80 specially interacts with histone
      variant H2A.Z and the H2A.Z enrichments at CPS1 and GA3ox2 are decreased in
      OsINO80-knockdown mutants. Thus, our study identified a rice chromatin-remodeling
      factor, OsINO80, and demonstrated that OsINO80 is involved in regulation of the
      GA biosynthesis pathway and plays critical functions for many aspects of rice
      plant growth and development.

PMID- 29045008
TI  - Poly(ionic liquids)-coated stainless-steel wires packed into a polyether ether
      ketone tube for in-tube solid-phase microextraction.
AB  - An in-tube solid-phase microextraction device was developed by packing poly(ionic
      liquids)-coated stainless-steel wires into a polyether ether ketone tube. An
      anion-exchange process was performed to enhance the extraction performance.
      Surface properties of poly(ionic liquids)-coated stainless-steel wires were
      characterized by scanning electron microscopy and energy dispersive X-ray
      spectrometry. The extraction device was connected to high-performance liquid
      chromatography equipment to build an online enrichment and analysis system. Ten
      polycyclic aromatic hydrocarbons were used as model analytes, and important
      conditions including extraction time and desorption time were optimized. The
      enrichment factors from 268 to 2497, linear range of 0.03-20 MUg/L, detection
      limits of 0.010-0.020 MUg/L, extraction and preparation repeatability with
      relative standard deviation less than 1.8 and 19%, respectively were given by the
      established online analysis method. It has been used to detect polycyclic
      aromatic hydrocarbons in environmental samples, with the relative recovery (5, 10
      MUg/L) in the range of 85.1-118.9%.

PMID- 29045009
TI  - Trends in non-lactation breast abscesses in a tertiary hospital setting.
AB  - BACKGROUND: The aim of this paper was to retrospectively review non-lactation
      breast abscesses treated in Princess Alexandra Hospital over a 10-year period and
      to illustrate the trends in size, risk factors, microbiological profile and
      management. METHODS: A computerized search of the medical records was undertaken
      to identify all adult patients with a diagnosis of breast abscesses during June
      2005-June 2015. Patients concurrently breastfeeding were excluded. A
      retrospectively review of the clinical records was performed. RESULTS: Eighty
      five abscesses were identified in 77 patients. The median patient age was 45
      years and 93.7% were females. Smoking and diabetes mellitus were associated with
      a longer inpatient hospital stay. There was a significant difference in
      microbiology of abscesses in relation to size. Smaller abscesses (<=3.0 cm)
      predominantly had mixed anaerobes (54%), whereas larger abscesses had a dominance
      of Staphylococcus aureus (29%) and other aerobic microbes (33%) (P < 0.05). Seven
      percent of all abscesses had methicillin-resistant S. aureus. Flucloxacillin was
      prescribed solely in majority of the cases (45%) with addition of suitable mixed
      anaerobic cover in 12% cases. Of the 85 abscesses, 58.8% were managed non
      operatively with antibiotics +/- percutaneous drainage. Percutaneous aspiration
      had a shorter inpatient stay compared with patients who underwent operative
      management. CONCLUSION: This represents the first Australian study solely
      analysing non-lactation breast abscess. Size was correlated significantly to
      characteristic bacteriology and empiric therapy should include both aerobic and
      anaerobic cover. The majority of non-lactation breast abscesses can be managed
      non-operatively with a combination of antibiotics and percutaneous aspiration.

PMID- 29045010
TI  - Characterization of carotenoids in Rhodothermus marinus.
AB  - Rhodothermus marinus, a marine aerobic thermophile, was first isolated from an
      intertidal hot spring in Iceland. In recent years, the R. marinus strain PRI 493
      has been genetically modified, which opens up possibilities for targeted
      metabolic engineering of the species, such as of the carotenoid biosynthetic
      pathway. In this study, the carotenoids of the R. marinus type-strain DSM 4252T ,
      strain DSM 4253, and strain PRI 493 were characterized. Bioreactor cultivations
      were used for pressurized liquid extraction and analyzed by ultra-high
      performance supercritical fluid chromatography with diode array and quadropole
      time-of-flight mass spectrometry detection (UHPSFC-DAD-QTOF/MS). Salinixanthin, a
      carotenoid originally found in Salinibacter ruber and previously detected in
      strain DSM 4253, was identified in all three R. marinus strains, both in the
      hydroxylated and nonhydroxylated form. Furthermore, an additional and
      structurally distinct carotenoid was detected in the three strains. MS/MS
      fragmentation implied that the mass difference between salinixanthin and the
      novel carotenoid structure corresponded to the absence of a 4-keto group on the
      beta-ionone ring. The study confirmed the lack of carotenoids for the strain SB
      71 (DeltatrpBDeltapurAcrtBI'::trpB) in which genes encoding two enzymes of the
      proposed pathway are partially deleted. Moreover, antioxidant capacity was
      detected in extracts of all the examined R. marinus strains and found to be 2-4
      times lower for the knock-out strain SB-71. A gene cluster with 11 genes in two
      operons in the R. marinusDSM 4252T genome was identified and analyzed, in which
      several genes were matched with carotenoid biosynthetic pathway genes in other
      organisms.

PMID- 29045011
TI  - Consumer health information seeking in social media: a literature review.
AB  - OBJECTIVE: The objective of this literature review was to summarise current
      research regarding how consumers seek health-related information from social
      media. Primarily, we hope to reveal characteristics of existing studies
      investigating the health topics that consumers have discussed in social media,
      ascertaining the roles social media have played in consumers' information-seeking
      processes and discussing the potential benefits and concerns of accessing
      consumer health information in social media. METHODS: The Web of Science Core
      Collection database was searched for existing literature on consumer health
      information seeking in social media. The search returned 214 articles, of which
      21 met the eligibility criteria following review of full-text documents.
      CONCLUSION: Between 2011 and 2016, twenty-one studies published explored various
      topics related to consumer information seeking in social media. These ranged from
      online discussions on specific diseases (e.g. diabetes) to public health concerns
      (e.g. pesticide residues). Consumers' information needs vary depending on the
      health issues of interest. Benefits of health seeking on social media, in
      addition to filling a need for health information, include the social and
      emotional support health consumers gain from peer-to-peer interactions. These
      benefits, however, are tempered by concerns of information quality and authority
      and lead to decreased consumer engagement.

PMID- 29045012
TI  - Photodynamic therapy inhibits melanogenesis through paracrine effects by
      keratinocytes and fibroblasts.
AB  - Photodynamic therapy (PDT) is a treatment option for skin cancer and premalignant
      skin diseases and exhibits rejuvenation effects, including reducing fine wrinkles
      and whitening, on aged skin. In this study, we investigated the mechanism
      underlying the whitening effects of PDT on melanocytes (MCs) in vitro and in
      vivo. Exposure of MCs to PDT in vitro reduced their melanin content and
      tyrosinase activity without, however, affecting cell survival. Interestingly,
      melanogenesis was also inhibited by exposing MCs to conditioned media of PDT
      treated keratinocytes or dermal fibroblasts. This paracrine effect was likely due
      to a decreased release of melanocyte-stimulating cytokines such as Kit ligand and
      hepatocyte growth factor from these cells. Furthermore, we observed that PDT
      reduced mottled hyperpigmentation of photoaged patient skin in vivo, highlighting
      the clinical importance of skin whitening by PDT.

PMID- 29045013
TI  - Is there a relationship between melanocytes and sensorineural hearing loss?
      Clinical evaluation of 51 patients with alopecia areata.

PMID- 29045014
TI  - Efficacy and toxicity of pegylated liposomal doxorubicin-based chemotherapy in
      early-stage breast cancer: a multicenter retrospective case-control study.
AB  - AIM: PEGylated liposomal doxorubicin (PLD) has comparable efficacy and differing
      toxicity from conventional anthracyclines used to treat advanced breast cancer.
      This study compared disease-free survival and toxicity between PLD-based and
      conventional anthracycline-based regimens as adjuvant treatments for early-stage
      breast cancer. METHODS: We analyzed disease-free survival (DFS) rates, and
      adverse events in 102 women with early-stage (I-IIIa) breast cancer who received
      adjuvant PLD-based chemotherapy from 2002 to 2008. Each patient was matched for
      age, stage at diagnosis, HER-2 expression and hormone therapy use to a patient
      treated with an epirubicin-based regimen. Fisher's exact and Pearson's chi-square
      tests were used for categorical data analysis. Kaplan-Meier analysis and Cox
      regression models were used to analyze DFS. RESULTS: DFS at 5 years was 81.3% for
      PLD-based regimen and 82.3% for epirubicin-based regimen. This difference was not
      significant (p = 0.939). Stage IIIa disease was associated with a shorter DFS in
      univariate analysis (p = 0.048). In multivariate analysis that controlled for
      adjuvant treatment, age at diagnosis, stage, HER-2 expression, type of surgery
      and hormone and radiation therapy, stage IIIa disease (P = 0.023) and lack of
      hormone therapy (P = 0.024) were each independently associated with shorter DFS.
      Adverse events were evaluated, and with the exception of hand-foot syndrome, more
      grade 3 and 4 toxicities occurred in patients who received epirubicin-based
      regimens than in those given PLD-based regimens. CONCLUSION: For patients with
      early-stage breast cancer who received PLD-based adjuvant chemotherapy, 5-year
      DFS was comparable and toxicity was acceptable, yet different from those of
      patients who received epirubicin-based regimens.

PMID- 29045016
TI  - Liquid Crystalline Networks toward Regenerative Medicine and Tissue Repair.
AB  - The communication reports the use of liquid crystalline networks (LCNs) for
      engineering tissue cultures with human cells. Their ability as cell scaffolds for
      different cell lines is demonstrated. Preliminary assessments of the material
      biocompatibility are performed on human dermal fibroblasts and murine muscle
      cells (C2C12), demonstrating that coatings or other treatments are not needed to
      use the acrylate-based materials as support. Moreover, it is found that adherent
      C2C12 cells undergo differentiation, forming multinucleated myotubes, which show
      the typical elongated shape, and contain bundles of stress fibers. Once
      biocompatibility is demonstrated, the same LCN films are used as a substrate for
      culturing human induced pluripotent stem cell-derived cardiomyocites (hiPSC-CMs)
      proving that LCNs are capable to develop adult-like dimensions and a more mature
      cell function in a short period of culture in respect to standard supports. The
      demonstrated biocompatibility together with the extraordinary features of LCNs
      opens to preparation of complex cell scaffolds, both patterned and stimulated,
      for dynamic cell culturing. The ability of these materials to improve cell
      maturation and differentiation will be developed toward engineered heart and
      skeletal muscular tissues exploring regenerative medicine toward bioartificial
      muscles for injured sites replacement.

PMID- 29045015
TI  - The small-molecule MERTK inhibitor UNC2025 decreases platelet activation and
      prevents thrombosis.
AB  - : Essentials Signaling by Gas6 through Tyro3/Axl/Mer receptors is essential for
      stable platelet aggregation. UNC2025 is a small molecule inhibitor of the Mer
      tyrosine kinase. UNC2025 decreases platelet activation in vitro and thrombus
      formation in vivo. UNC2025's anti-platelet effect is synergistic with inhibition
      of the ADP receptor, P2Y12 . SUMMARY: Background Growth arrest-specific protein 6
      signals through the TAM (TYRO-3-AXL-MERTK) receptor family, mediating platelet
      activation and thrombus formation via activation of the aggregate-stabilizing
      alphaIIb beta3 integrin. Objective To describe the antithrombotic effects
      mediated by UNC2025, a small-molecule MERTK tyrosine kinase inhibitor. Methods
      MERTK phosphorylation and downstream signaling were assessed by immunoblotting.
      Light transmission aggregometry, flow cytometry and microfluidic analysis were
      used to evaluate the impact of MERTK inhibition on platelet activation and
      stability of aggregates in vitro. The effects of MERTK inhibition on arterial and
      venous thrombosis, platelet accumulation at microvascular injury sites and tail
      bleeding times were determined with murine models. The effects of combined
      treatment with ADP-P2Y1&12 pathway antagonists and UNC2025 were also evaluated.
      Results and Conclusions Treatment with UNC2025 inhibited MERTK phosphorylation
      and downstream activation of AKT and SRC, decreased platelet activation, and
      protected animals from pulmonary embolism and arterial thrombosis without
      increasing bleeding times. The antiplatelet effect of UNC2025 was enhanced in
      combination with ADP-P2Y1&12 pathway antagonists, and a greater than additive
      effect was observed when these two agents with different mechanisms of inhibition
      were coadministered. TAM kinase signaling represents a potential therapeutic
      target, as inhibition of this axis, especially in combination with ADP-P2Y
      pathway antagonism, mediates decreased platelet activation, aggregate stability,
      and thrombus formation, with less hemorrhagic potential than current treatment
      strategies. The data presented here also demonstrate antithrombotic activity
      mediated by UNC2025, a novel translational agent, and support the development of
      TAM kinase inhibitors for clinical applications.

PMID- 29045017
TI  - Connecting Biology to Electronics: Molecular Communication via Redox Modality.
AB  - Biology and electronics are both expert at for accessing, analyzing, and
      responding to information. Biology uses ions, small molecules, and macromolecules
      to receive, analyze, store, and transmit information, whereas electronic devices
      receive input in the form of electromagnetic radiation, process the information
      using electrons, and then transmit output as electromagnetic waves. Generating
      the capabilities to connect biology-electronic modalities offers exciting
      opportunities to shape the future of biosensors, point-of-care medicine, and
      wearable/implantable devices. Redox reactions offer unique opportunities for bio
      device communication that spans the molecular modalities of biology and
      electrical modality of devices. Here, an approach to search for redox information
      through an interactive electrochemical probing that is analogous to sonar is
      adopted. The capabilities of this approach to access global chemical information
      as well as information of specific redox-active chemical entities are illustrated
      using recent examples. An example of the use of synthetic biology to recognize
      external molecular information, process this information through intracellular
      signal transduction pathways, and generate output responses that can be detected
      by electrical modalities is also provided. Finally, exciting results in the use
      of redox reactions to actuate biology are provided to illustrate that synthetic
      biology offers the potential to guide biological response through electrical
      cues.

PMID- 29045018
TI  - Patient, disease, and treatment factors associated with overall survival in
      esthesioneuroblastoma.
AB  - BACKGROUND: Esthesioneuroblastomas (ENB) are uncommon and data regarding outcomes
      are often limited to single-institution series. The National Cancer Database
      (NCDB), which contains outcomes information from treatment centers across the
      United States, represents an opportunity to evaluate outcomes for rare diseases
      such as ENB across multiple institutions. METHODS: The NCDB was queried for
      location codes corresponding to the nasal cavity and paranasal sinuses and the
      histology code for ENB. Multivariate analyses were performed to evaluate for
      contributing factors to overall survival. RESULTS: A total of 1225 patients with
      ENB met the inclusion criteria. The 5-year overall survival was 76.2% (95%
      confidence interval [CI], 73.4-79.0%). Overall survival was associated with
      Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age,
      and gender (p < 0.05). Multivariate analysis demonstrated that, compared with
      surgery alone, surgery followed by radiation without chemotherapy had improved
      all-cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40-0.95). Surgery with
      chemotherapy alone was associated with increased odds of all-cause mortality (OR,
      4.86; 95% CI, 2.31-10.25). Multivariate subanalysis for Kadish stages A and B
      demonstrated no difference in survival between surgery and surgery followed by
      radiation, but surgery followed by chemoradiation had worse overall survival (OR,
      3.03; 95% CI, 1.07-8.56). For Kadish stage C, surgery followed by radiation had
      improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24
      0.81). CONCLUSION: The most common treatment for ENB is surgery followed by
      radiation, which is associated with the highest overall survival. The role of
      adjunctive chemotherapy needs to be re-evaluated in further studies.

PMID- 29045019
TI  - An Easy-to-Machine Electrochemical Flow Microreactor: Efficient Synthesis of
      Isoindolinone and Flow Functionalization.
AB  - Flow electrochemistry is an efficient methodology to generate radical
      intermediates. An electrochemical flow microreactor has been designed and
      manufactured to improve the efficiency of electrochemical flow reactions. With
      this device only little or no supporting electrolytes are needed, making
      processes less costly and enabling easier purification. This is demonstrated by
      the facile synthesis of amidyl radicals used in intramolecular hydroaminations to
      produce isoindolinones. The combination with inline mass spectrometry facilitates
      a much easier combination of chemical steps in a single flow process.

PMID- 29045020
TI  - The Selective Role of Long-Range Forces in the Stereodynamics of Ion-Molecule
      Reactions: The He+ +Methyl Formate Case From Guided-Ion-Beam Experiments.
AB  - Long-range intermolecular forces play a crucial role in controlling the outcome
      of ion-molecule chemical reactions, such as those determining the disappearance
      of organic or inorganic "complex" molecules recently detected in various regions
      of the interstellar medium due to collisions with abundant interstellar atomic
      ions (e.g. H+ and He+ ). Theoretical treatments, for example, based on simple
      capture models, are nowadays often adopted to evaluate the collision-energy
      dependence of reactive cross sections and the temperature dependent rate
      coefficients of many ion-molecule reactions. The obtained results are widely used
      for the modelling of phenomena occurring in different natural environments or
      technological applications such as astrophysical and laboratory plasmas. Herein
      it is demonstrated, through a combined experimental and theoretical investigation
      on a prototype ion-molecule reaction (He+ +methyl formate), that the dynamics,
      investigated in detail, shows some intriguing features that can lead to rate
      coefficients at odds with the expectations (e.g. Arrhenius versus anti-Arrhenius
      behaviour). Therefore, this study casts light on some new and general guidelines
      to be properly taken into account for a suitable evaluation of rate coefficients
      of ion-molecule reactions.

PMID- 29045022
TI  - Recent advances in pediatric rheumatology: October to December 2016.

PMID- 29045021
TI  - Reduced dietary intake of micronutrients with antioxidant properties negatively
      impacts muscle health in aged mice.
AB  - BACKGROUND: Inadequate intake of micronutrients with antioxidant properties is
      common among older adults and has been associated with higher risk of frailty,
      adverse functional outcome, and impaired muscle health. However, a causal
      relationship is less well known. The aim was to determine in old mice the impact
      of reduced dietary intake of vitamins A/E/B6/B12/folate, selenium, and zinc on
      muscle mass, oxidative capacity, strength, and physical activity (PA) over time.
      METHODS: Twenty-one-month-old male mice were fed either AIN-93-M (control) or a
      diet low in micronutrients with antioxidant properties (=LOWOX-B: 50% of mouse
      recommended daily intake of vitamins A, E, B6, and B12, folate, selenium, and
      zinc) for 4 months. Muscle mass, grip strength, physical activity (PA), and
      general oxidative status were assessed. Moreover, muscle fatigue was measured of
      m. extensor digitorum longus (EDL) during an ex vivo moderate exercise protocol.
      Effects on oxidative capacity [succinate dehydrogenase (SDH) activity], muscle
      fibre type, number, and fibre cross-sectional area (fCSA) were assessed on m.
      plantaris (PL) using histochemistry. RESULTS: After 2 months on the diet,
      bodyweight of LOWOX-B mice was lower compared with control (P < 0.0001), mainly
      due to lower fat mass (P < 0.0001), without significant differences in food
      intake. After 4 months, oxidative status of LOWOX-B mice was lower, demonstrated
      by decreased vitamin E plasma levels (P < 0.05) and increased liver
      malondialdehyde levels (P = 0.018). PA was lower in LOWOX-B mice (P < 0.001 vs.
      control). Muscle mass was not affected, although PL-fCSA was decreased (~16%; P =
      0.028 vs. control). SDH activity and muscle fibre type distribution remained
      unaffected. In LOWOX-B mice, EDL force production was decreased by 49.7% at lower
      stimulation frequencies (P = 0.038), and fatigue resistance was diminished (P =
      0.023) compared with control. CONCLUSIONS: Reduced dietary intake of vitamins A,
      E, B6, and B12, folate, selenium, and zinc resulted in a lower oxidative capacity
      and has major impact on muscle health as shown by decreased force production and
      PA, without effects on muscle mass. The reduced fCSA in combination with similar
      SDH activity per fibre might explain the reduced oxidative capacity resulting in
      the increased fatigue after exercise in LOWOX-B mice.

PMID- 29045023
TI  - More advanced disease and worse survival in cryptogenic compared to viral
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Although hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections remain major risk factors for hepatocellular carcinoma (HCC), non
      viral causes of HCC, particularly non-alcoholic fatty liver disease (NAFLD), are
      becoming increasingly prevalent. The aim of this study was to compare the
      clinical characteristics and survival of cryptogenic and viral HCC. METHODS: We
      conducted a retrospective cohort study involving 3878 consecutive HCC patients
      seen at two tertiary centres in the United States and one in Taiwan from 2004 to
      2014. We compared the clinical characteristics, treatment and survival of
      patients by underlying aetiology: cryptogenic (n = 696), HBV (n = 1304) or HCV (n
      = 1878). RESULTS: Cirrhosis was present in 66.8% of the cryptogenic HCC patients,
      compared with 74.7% of HBV-related HCC (HBV-HCC) (P = .001) and 85.9% of HCV-HCC
      (P < .001). Compared to viral HCC, cryptogenic HCC patients presented with larger
      tumours and at later stages of disease. Five-year overall survival was 16.3%
      among cryptogenic HCC patients compared with 31.9% among HBV-HCC patients and
      27.7% among HCV-HCC patients (P < .001 for both by the log-rank test). HCC
      aetiology was not an independent predictor of survival, though ethnicity,
      cirrhosis status, meeting Milan criteria and treatment allocation were.
      CONCLUSIONS: Compared with viral HCC patients, those with cryptogenic HCC had
      lower prevalence of cirrhosis, were diagnosed with larger tumours at more
      advanced stages of disease, and had poorer overall survival. Additional efforts
      are needed to identify patients at risk of cryptogenic HCC and to identify
      cryptogenic HCC at earlier stages of disease.

PMID- 29045025
TI  - Do preoperative oral antibiotics increase Clostridium difficile infection rates?
      An analysis of 13 959 colectomy patients.
AB  - AIM: The aim of this study was to determine whether or not preoperative oral
      antibiotic preparation (POAP) increases the rate of Clostridium difficile colitis
      (CDC) in patients undergoing colectomy. METHOD: In 2015, data for colectomies had
      been collected prospectively and recorded in the targeted colectomy option of the
      American College of Surgeons National Surgical Quality Improvement Program (ACS
      NSQIP). This was available for retrospective analysis. Data available for
      analysis included elective and emergency status, POAP, surgical approach, primary
      anastomosis and CDC status. The effect of POAP on CDC was analysed and risk
      adjusted for 14 separate preoperative variables. RESULTS: In all, 13 959 adult
      patients underwent a colectomy in 2015 (POAP group 5311 and non- POAP group
      8648). The overall rate of CDC in colectomy patients was 1.6% (227/13 959). On
      univariate analysis, CDC was significantly less common in the POAP group than in
      the non-POAP group (1.2% vs 1.9%, P = 0.003). Univariate analysis of a further 41
      preoperative variables revealed 14 to be associated with CDC. However, after risk
      adjustment with these 14 variables, POAP lost its statistical significance
      (adjusted OR 0.902, 95% CI 0.584-1.486, P = 0.685). Only patients with pre
      existing systemic inflammatory response syndrome appeared to be at increased risk
      of CDC (adjusted OR 2.154, 95% CI 1.139-4.074, P = 0.018). CONCLUSION: At the
      very least this study suggests it is safe to use POAP in colectomy patients
      without increasing the rate of CDC unless they have pre-existing systemic
      inflammatory response syndrome.

PMID- 29045024
TI  - In Vivo Characterizations of the Immune Properties of Sericin: An Ancient
      Material with Emerging Value in Biomedical Applications.
AB  - The biosafety of sericin remains controversial. The misunderstanding regarding
      sericin causing adverse biological responses have been clarified by extensively
      reviewing relevant literatures and experimentally demonstrating that sericin
      exhibits mild inflammatory responses, negligible allergenicity, and low
      immunogenicity in vivo. This study supports that sericin is biosafe as a natural
      biomaterial.

PMID- 29045026
TI  - Feasibility of laparoscopic surgery after stent insertion for obstructive
      colorectal cancer.
AB  - INTRODUCTION: A growing number of patients with obstructive colorectal cancer are
      being treated with self-expanding metallic stents (SEMS) followed by laparoscopic
      resection. The aim of this study was to assess the feasibility of stent insertion
      and laparoscopic surgery for obstructive colorectal cancer and to compare these
      outcomes to regular laparoscopic surgery for non-obstructive colorectal cancer.
      METHODS: We retrospectively analyzed the outcomes of patients with a malignant
      colonic obstruction who underwent SEMS placement followed by elective
      laparoscopic resection. The comparison was made between stent-laparoscopy and
      laparoscopy alone for non-obstructive colorectal cancer. RESULTS: Colonic
      stenting as a bridge to surgery was successful in 97.1% of all cases. Fifteen
      patients underwent an elective laparoscopic surgery for left-sided colon and
      rectal cancer after SEMS. The mean interval from SEMS insertion to laparoscopic
      surgery was 21.5 days. There was no conversion to open surgery and no need for a
      diverting stoma. One patient (6.7%) experienced paralytic ileus. Our comparison
      of stent-laparoscopy to regular laparoscopy for non-obstructive colorectal cancer
      treatment showed comparable short-term postoperative outcomes with the exception
      of blood loss, which was greater in the stent-laparoscopy group. CONCLUSION:
      Elective laparoscopic surgery after colonic stenting is a safe and feasible
      strategy for the treatment of an acute malignant colonic obstruction.

PMID- 29045028
TI  - Biological effects of Er:YAG laser irradiation on the proliferation of primary
      human gingival fibroblasts.
AB  - We investigated the biological effects of Er:YAG laser (2940-nm; DELight, HOYA
      ConBio, Fremont, California) irradiation at fluences of 3.6, 4.2, 4.9, 6.3, 8.1
      or 9.7 J cm-2 at 20 or 30 Hz for 20 or 30 seconds on primary human gingival
      fibroblasts (HGFs). Irradiation at 6.3 J cm-2 promoted maximal cell
      proliferation, determined by WST-8 assay and crystal violet staining, but was
      accompanied by lactate dehydrogenase release, on day 3 post-irradiation.
      Elevation of ATP level, Ki67 staining, and cyclin-A2 mRNA expression confirmed
      that Er:YAG affected the cell cycle and increased the number of proliferating
      cells. Transmission electron microscopy showed alterations of mitochondria and
      ribosomal endoplasmic reticulum (ER) at 3 hours post-irradiation at 6.3 J cm-2 ,
      and the changes subsided after 24 hours, suggesting transient cellular injury.
      Microarray analysis revealed up-regulation of 21 genes involved in heat-related
      biological responses and ER-associated degradation. The mRNA expression of heat
      shock protein 70 family was increased, as validated by Real-time PCR. Surface
      temperature measurement confirmed that 6.3 J cm-2 generated heat (40.9 degrees C
      post-irradiation). Treatment with 40 degrees C-warmed medium increased
      proliferation. Laser-induced proliferation was suppressed by inhibition of
      thermosensory transient receptor potential channels. Thus, despite causing
      transient cellular damage, Er:YAG laser irradiation at 6.3 J cm-2 strongly
      potentiated HGF proliferation via photo-thermal stress, suggesting potential
      wound-healing benefit.

PMID- 29045027
TI  - Step-Up Synthesis of Periodic Mesoporous Organosilicas with a Tyrosine Framework
      and Performance in Horseradish Peroxidase Immobilization.
AB  - New amino-acid-bridged periodic mesoporous organosilicas (PMOs) were constructed
      by hydrolysis and condensation reactions under acid conditions in the presence of
      a template. The tyrosine bissilylated organic precursor (TBOS) was first prepared
      through a multistep reaction by using tyrosine (a natural amino acid) as the
      starting material. PMOs with the tyrosine framework (Tyr-PMOs) were constructed
      by simultaneously using TBOS and tetraethoxysilane as complex silicon sources in
      the condensation process. All the Tyr-PMOs materials were characterized by XRD,
      FTIR spectroscopy, N2 adsorption-desorption, TEM, SEM, and solid-state 29 Si NMR
      spectroscopy to confirm the structure. The horseradish peroxidase (HRP) enzyme
      was first immobilized on these new Tyr-PMOs materials. Optimal conditions for
      enzyme adsorption included a temperature of 40  degrees C, a time of 8 h, and a
      pH value of 7. Furthermore, the novel Tyr-PMOs materials could store HRP for
      approximately 40 days and maintained the enzymatic activity, and the Tyr-PMOs-10
      % HRP with the best immobilization effect could be reused at least eight times.

PMID- 29045029
TI  - The Immunosuppressant Brasilicardin: Determination of the Biosynthetic Gene
      Cluster in the Heterologous Host Amycolatopsis japonicum.
AB  - Nocardia terpenica IFM 0406 is the producer of the immunosuppressants
      brasilicardins A-D. Brasilicardin is a promising compound because of its unique
      mode of action and its higher potency and reduced toxicity compared to today's
      standard drugs. However, production of brasilicardin is so far hampered as
      Nocardia terpenica IFM 0406 synthesizes brasilicardin in only low amounts and
      represents a human pathogen (biosafety level 2 BSL2). In order to achieve a safe
      and high yield production of brasilicardin A (BraA), the authors heterologously
      express the brasilicardin gene cluster in the nocardioform actinomycete
      Amycolatopsis japonicum (A. japonicum::bcaAB01), which is fast growing,
      genetically accessible and closely related to N. terpenica IFM 0406. In A.
      japonicum::bcaAB01, four brasilicardin congeners, intermediates of the BraA
      biosynthesis, are produced. Investigation of the genes flanking the previously
      defined brasilicardin biosynthetic gene cluster revealed two novel genes (bra0,
      bra12), which are involved in brasilicardin biosynthesis: bra12 encodes a
      transcriptional activator of the brasilicardin gene cluster. bra0 codes for a
      dioxygenase involved in methoxylation of brasilicardin. Based on this finding the
      authors are able to revise the proposed brasilicardin biosynthesis.

PMID- 29045030
TI  - Drug Delivery to the Brain across the Blood-Brain Barrier Using Nanomaterials.
AB  - A major obstacle facing brain diseases such as Alzheimer's disease, multiple
      sclerosis, brain tumors, and strokes is the blood-brain barrier (BBB). The BBB
      prevents the passage of certain molecules and pathogens from the circulatory
      system into the brain. Therefore, it is nearly impossible for therapeutic drugs
      to target the diseased cells without the assistance of carriers. Nanotechnology
      is an area of growing public interest; nanocarriers, such as polymer-based, lipid
      based, and inorganic-based nanoparticles can be engineered in different sizes,
      shapes, and surface charges, and they can be modified with functional groups to
      enhance their penetration and targeting capabilities. Hence, understanding the
      interaction between nanomaterials and the BBB is crucial. In this Review, the
      components and properties of the BBB are revisited and the types of nanocarriers
      that are most commonly used for brain drug delivery are discussed. The properties
      of the nanocarriers and the factors that affect drug delivery across the BBB are
      elaborated upon in this review. Additionally, the most recent developments of
      nanoformulations and nonconventional drug delivery strategies are highlighted.
      Finally, challenges and considerations for the development of brain targeting
      nanomedicines are discussed. The overall objective is to broaden the
      understanding of the design and to develop nanomedicines for the treatment of
      brain diseases.

PMID- 29045031
TI  - The triangular rotation advancement flap for congenital longitudinal earlobe
      cleft.

PMID- 29045032
TI  - A retrospective review of six hundred and nineteen cases to determine the
      prevalence and factors associated with revision endoscopic sinus surgery in AFRS
      vs NON-AFRS patients.

PMID- 29045033
TI  - A Novel trans-1-(9-Anthryl)-2-phenylethene Derivative Containing a
      Phenanthroimidazole Unit for Application in Organic Light-Emitting Diodes.
AB  - Aryl-substituted phenanthroimidazoles (PIs) have attracted tremendous attention
      in the field of organic light-emitting diodes (OLEDs), because they are simple to
      synthesize and have excellent thermal properties, high photoluminescence quantum
      yields (PLQYs), and bipolar properties. Herein, a novel blue-green emitting
      material, (E)-2-{4'-[2-(anthracen-9-yl)vinyl]-[1,1'-biphenyl]-4-yl}-1-phenyl-1H
      phenanthro[9,10-d]imidazole (APE-PPI), containing a t-APE [1-(9-anthryl)-2
      phenylethene] core and a PI moiety was designed and synthesized. Owing to the PI
      skeleton, APE-PPI possesses high thermal stability and a high PLQY, and the
      compound exhibits bipolar transporting characteristics, which were identified by
      single-carrier devices. Nondoped blue-green OLEDs with APE-PPI as the emitting
      layer show emission at lambda=508 nm, a full width at half maximum of 82 nm, a
      maximum brightness of 9042 cd m-2 , a maximum current efficiency of 2.14 cd A-1 ,
      and Commission Internationale de L'Eclairage (CIE) coordinates of (0.26, 0.55).
      Furthermore, a white OLED (WOLED) was fabricated by employing APE-PPI as the blue
      green emitting layer and 4-(dicyanomethylene)-2-tert-butyl-6-(1,1,7,7
      tetramethyljulolidin-4-yl-vinyl)-4H-pyran (DCJTB) doped in tris-(8
      hydroxyquinolinato)aluminum (Alq3 ) as the red-green emitting layer. This WOLED
      exhibited a maximum brightness of 10029 cd m-2 , a maximum current efficiency of
      16.05 cd A-1 , CIE coordinates of (0.47, 0.47), and a color rendering index (CRI)
      of 85. The high performance of APE-PPI-based devices suggests that the t-APE and
      PI combination can potentially be used to synthesize efficient electroluminescent
      materials for WOLEDs.

PMID- 29045034
TI  - Differential expression profiles of circulating microRNAs in newborns associated
      to maternal pregestational overweight and obesity.
AB  - BACKGROUND: The perinatal environment has a role in the establishment of altered
      metabolic and inflammatory responses, and could be modulated by microRNAs
      regulating immune and metabolic processes. OBJECTIVE: To analyze the expression
      profile of four circulating microRNAs and cytokine serum concentrations in
      neonates born to overweight and obese women. METHODS: Pregnant women were
      included and grouped by pregestational body mass index (21 with normal weight, 10
      overweight and 10 obese women). A peripheral blood sample was obtained from
      newborn infants and used to determine circulating miRNAs expression and cytokine
      serum concentrations. RESULTS: There were significant differences in the
      expression of three microRNAs between newborns of pregestational obese women and
      newborns from pregestational normal weight women: miR-155 (p = 0.03), miR-181a (p
      = 0.02) and miR-221 (p = 0.04). A significant reduction in IL-1beta (p = 0.005)
      expression was also found in newborns of overweight women; although this cytokine
      was also diminished in newborns of obese women, this was not statistically
      significant. An association between IL-1beta concentrations and miR-146a and miR
      221 expression was also observed. CONCLUSIONS: Expression of miR-155, miR-181a
      and miR-221 differs in infants born to obese women compared with infants born to
      normal weight women. Changes in microRNA expression could participate in the
      epigenetic foetal programming of metabolic disorders in children born to obese
      women.

PMID- 29045035
TI  - Nitrogen-doped carbon dots as a fluorescent probe for the highly sensitive
      detection of Ag+ and cell imaging.
AB  - An easy hydrothermal synthesis strategy was applied to synthesize green-yellow
      emitting nitrogen-doped carbon dots (N-CDs) using 1,2-diaminobenzene as the
      carbon source, and dicyandiamide as the dopant. The nitrogen-doped CDs resulted
      in improvement in the electronic characteristics and surface chemical activities.
      N-CDs exhibited bright fluorescence emission and could response to Ag+
      selectively and sensitively. Other ions produced nearly no interference. A N-CDs
      based fluorescent probe was then applied to sensitively determine Ag+ with a
      detection limit of 5 * 10-8  mol/L. The method was applied to the determination
      of Ag+ dissolved in water. Finally, negligibly cytotoxic, excellently
      biocompatibile, and highly fluorescent carbon dots were applied for HepG2 cell
      imaging and the quenched fluorescence by adding Ag+ , which indicated its
      potential applications.

PMID- 29045036
TI  - Endoplasmic reticulum stress regulates oxygen-glucose deprivation-induced
      parthanatos in human SH-SY5Y cells via improvement of intracellular ROS.
AB  - AIMS: Endoplasmic reticulum (ER) stress has been demonstrated to regulate
      neuronal death caused by ischemic insults via activation of apoptosis, but it
      still remains unclear whether ER stress participates in regulation of
      parthanatos, a new type of programmed cell death characterized by PARP-1
      overactivation and intracellular accumulation of PAR polymer. METHODS: we used
      oxygen-glucose deprivation (OGD) and human SH-SY5Y cells to simulate neuronal
      damage caused by ischemia. RESULTS: Oxygen-glucose deprivation induced time
      dependent death in SH-SY5Y cells, which was accompanied with upregulation of PARP
      1, accumulation of PAR polymer, decline of mitochondrial membrane potentials and
      nuclear translocation of AIF. Pharmacological inhibition of PARP-1 with its
      specific inhibitor 3AB rescued OGD-induced cell death, as well as prevented PAR
      polymer accumulation, mitochondrial depolarization, and AIF translocation into
      nucleus. Similar results could be found when PARP-1 was genetically knocked down
      with SiRNA. These indicated that OGD triggered parthanatos in SH-SY5Y cells.
      Then, we found inhibition of overproduction of ROS with antioxidant NAC
      attenuated obviously OGD-induced parthanatos in SH-SY5Y cells, suggesting ROS
      regulated OGD-induced parthanatos. Additionally, OGD also induced upregulation of
      ER stress-related proteins. Mitigation of ER stress with chemical chaperone 4-PBA
      or trehalose suppressed significantly OGD-induced overproduction of ROS, PARP-1
      upregulation, PAR polymer accumulation, and nuclear accumulation of AIF, and cell
      death in SH-SY5Y cells. CONCLUSION: Endoplasmic reticulum stress regulates OGD
      induced parthanatos in human SH-SY5Y cells via improvement of intracellular ROS.

PMID- 29045037
TI  - Autoantibodies Targeting Ficolin-2 in Systemic Lupus Erythematosus Patients With
      Active Nephritis.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem inflammatory
      disease characterized by the production of various autoantibodies. The aim of
      this study was to investigate the presence of anti-ficolin-2 antibodies in SLE
      patients and to evaluate the association between the levels of these
      autoantibodies, clinical manifestations, and disease activity. METHODS: This is a
      comparative study using a cohort of 165 SLE patients and 48 healthy subjects. SLE
      patients were further divided into 2 groups (low disease activity [SLE Disease
      Activity Index (SLEDAI) score <=4, n = 88] and high disease activity [SLEDAI
      score >4, n = 77]). Clinical manifestations were defined according to the
      physician in charge. Active lupus nephritis (LN) was documented by kidney biopsy.
      Detection of anti-ficolin-2 antibodies was performed by enzyme-linked
      immunosorbent assay. RESULTS: Levels of anti-ficolin-2 autoantibodies were
      significantly higher in SLE patients as compared to healthy subjects and
      associated with SLEDAI score. They were found to be positive in 61 of 165 SLE
      patients (37%). The presence of anti-ficolin-2 antibodies was significantly
      related only to renal involvement, with a very high prevalence (86%) of anti
      ficolin-2 antibodies in SLE patients with active LN. Patients with active
      proliferative LN had significantly more positive anti-ficolin-2 antibodies than
      those with nonproliferative LN. The combination of anti-ficolin-2, anti-ficolin
      3, and anti-C1q demonstrated a very high specificity (98%) for the diagnosis of
      active LN. CONCLUSION: Our results support the usefulness of anti-ficolin-2 as a
      complementary serologic biomarker for the diagnosis of active lupus with renal
      manifestations.

PMID- 29045038
TI  - Knitting N-doped Hierarchical Porous Polymers to Stabilize Ultra-small Pd
      Nanoparticles for Solvent-Free Catalysis.
AB  - Hierarchical porous polymers with more than one pore size distributions can
      effectively support noble metal catalysts and circumvent the limitation of the
      diffusion of the reactants, and thus exhibit both excellent catalytic activity
      and superior diffusive properties. Herein, we report a simple one-step Friedel
      Crafts reaction to knit a series of benzene heterocycle monomers, such as indane,
      indoline, indole and tetrahydronaphthalene to obtain hierarchical porous polymers
      with high surface areas and/or abundant N sites. These polymers can be directly
      used to immobilize Pd ions, and stabilize Pd nanoparticles during the thermal
      reduction process to obtain Pd/polymer catalysts. In particular, indoline- and
      indole-based polymers with high N content up to 7 wt % exhibit outstanding
      ability to stabilize uniform ultrasmall Pd nanoparticles. The obtained Pd
      polymers exhibit excellent catalytic activity in the solvent-free oxidation of
      benzyl alcohol with O2 .

PMID- 29045039
TI  - Design of potent B-RafV600E inhibitors by multiple copy simulation search
      strategy.
AB  - B-Raf kinase is a vital intermedium in the mitogen-activated protein kinase
      (MAPK) signaling pathway, which transforms extracellular signals into cellular
      mechanisms. Mutations in this kinase, for instance, the most common V600E
      mutation, can lead to the ERK signaling pathologically activated and hence cause
      severe diseases such as somatic tumors. So far, the development of B-Raf
      inhibitors has made remarkable progress. However, the resistance and relapse of
      approved Raf drugs have been widely reported, and the optimization for old drugs
      and the discovery for new inhibitors still remain a significant task. In this
      study, we designed and evaluated a series of novel B-RafV600E inhibitors. A
      fragment library has been established before the docking simulation carried out
      using the MCSS strategy (multicopy simulation search). The appropriate fragments
      were reassembled to provide new candidate compounds, which were further screened
      by iterative docking simulations and molecular dynamics. Bioassays were carried
      out to evaluate the pharmacological profile of the compounds identified and
      synthesized. The result showed that compound 5n had an impressive enzyme
      inhibitory and antiproliferation activity, suggesting a promising potential in
      the future study.

PMID- 29045040
TI  - Neurexin gene family variants as risk factors for autism spectrum disorder.
AB  - : Increasing evidence suggests that abnormal synaptic function leads to neuronal
      developmental disorders and is an important component of the etiology of autism
      spectrum disorder (ASD). Neurexins are presynaptic cell-adhesion molecules that
      affect the function of synapses and mediate the conduction of nerve signals.
      Thus, neurexins are attractive candidate genes for autism. Since gene families
      have greater power to reveal genetic association than single genes, we designed
      this case-control study to investigate six genetic variants in three neurexin
      genes (NRXN1, NRXN2, and NRXN3) in a Chinese population including 529 ASD
      patients and 1,923 healthy controls. We found that two SNPs were significantly
      associated with ASD after false discovery rate (FDR) adjustment for multiple
      comparisons. The NRXN2 rs12273892 polymorphism T allele and AT genotype were
      significantly associated with increased risk of ASD (respectively: OR = 1.328,
      95% CI = 1.133-1.557, P < 0.001; OR = 1.528; 95% CI = 1.249-1.868, P < 0.001).
      The dominant model showed the same association (OR = 1.495, 95% CI = 1.231-1.816,
      P < 0.001). The NRXN3 rs12879016 polymorphism played a significant role in ASD
      susceptibility under the dominant model (OR = 0.747, 95% CI= 0.615-0.908, P =
      0.023), with the same trend detected for the G allele and GT genotype
      (respectively: OR = 0.811, 95% CI = 0.699-0.941, P = 0.036; OR = 0.755, 95% CI =
      0.615-0.928, P = 0.035). In conclusion, this study supports the importance of two
      genetic variants in the neurexin gene family in ASD susceptibility in China.
      Autism Res 2018, 11: 37-43. (c) 2017 International Society for Autism Research,
      Wiley Periodicals, Inc. LAY SUMMARY: Autism spectrum disorder (ASD) is a
      neurodevelopmental disorder that is highly heritable, and studies have found a
      number of candidate genes that might contribute to ASD. Neurexins are presynaptic
      cell-adhesion molecules that affect the function of synapses and mediate the
      conduction of nerve signals, and they play an important role in normal brain
      development and become candidate genes for autism. The purpose of our study is to
      explore the association between variants of the neurexins gene family and ASD in
      a Chinese population through a case-control study.

PMID- 29045041
TI  - Orbital and rotational atherectomy during percutaneous coronary intervention for
      coronary artery calcification.
AB  - Severe coronary artery calcification (CAC) increases the complexity of
      percutaneous coronary intervention (PCI) by inhibiting optimal stent expansion,
      leading to an increased risk of death, myocardial infarction, repeat
      revascularization, and stent thrombosis. Coronary atherectomy modifies and
      debulks calcified plaque to facilitate PCI. Although there is no clear consensus,
      and further studies are needed, the decision to perform atherectomy should be
      based upon the presence of fluoroscopic CAC or with the use of intravascular
      imaging. The management of CAC in the modern era relies on rotational and orbital
      atherectomy to prepare the lesion to facilitate stent delivery and optimal
      expansion. While the two technologies differ in equipment, technique, and
      mechanism of action, the available literature suggests similar efficacy and
      safety of the two systems, although head-to-head comparisons are limited. While
      rotational and orbital atherectomy have been shown to have excellent procedural
      success in terms of facilitating stent delivery, no system has been shown to
      reduce long-term major adverse cardiovascular events, although the definitive
      trial for orbital atherectomy has not been completed. Additional trials are
      needed to find the population who would derive the most benefit of atherectomy
      and to compare the two systems in a prospective manner.

PMID- 29045042
TI  - Conjugated Microporous Polymers for Heterogeneous Catalysis.
AB  - Conjugated microporous polymers (CMPs) are a class of crosslinked polymers that
      combine permanent micropores with pi-conjugated skeletons and possess three
      dimensional (3D) networks. Compared with conventional materials such as metal
      organic frameworks (MOFs) and covalent organic frameworks (COFs), CMPs usually
      have superior chemical and thermal stability. CMPs have made significant progress
      in heterogeneous catalysis in the past seven years. With a bottom-up strategy,
      catalytic moieties can be directly introduced into in the framework to produce
      heterogeneous CMP catalysts. Higher activity, stability, and selectivity can be
      obtained with heterogeneous CMP catalysts in comparison with their homogeneous
      analogs. In addition, CMP catalysts can be easily isolated and recycled. In this
      review, we focus on CMPs as an intriguing platform for developing various highly
      efficient and recyclable heterogeneous catalysts in organic reactions. The
      design, synthesis, and structure of these CMP catalysts are also discussed in
      this focus review.

PMID- 29045043
TI  - Non-oxidative Coupling of Methane to Ethylene Using Mo2 C/[B]ZSM-5.
AB  - Methane non-oxidative coupling to ethylene was investigated on Mo2 C/[B]ZSM-5
      catalyst at 923 K and atmospheric pressure. In contrast to Mo2 C/[Al]ZSM-5
      catalysts for methane aromatization, this material exhibits very high ethylene
      selectivity (>90 %) and low aromatics (benzene and naphthalene) selectivity. The
      much weaker Bronsted acidity of [B]ZSM-5 leads to a slow rate of ethylene
      oligomerization. The stability of the catalyst is greatly enhanced with 93 % of
      the initial reaction rate remaining after 18 h of time on stream. In-situ UV/VIS
      spectra indicate that prior to carburization, mono/binuclear Mo oxides are
      initially well dispersed onto the zeolite support. Mo carbides clusters, formed
      during carburization with methane, appear similar to clusters formed in [Al]ZSM
      5, as indicated by the X-ray Absorption Spectroscopy (XAS) data.

PMID- 29045044
TI  - The Pine-Needle-Inspired Structure of Zinc Oxide Nanorods Grown on Electrospun
      Nanofibers for High-Performance Flexible Supercapacitors.
AB  - Flexible supercapacitors with high electrochemical performance and stability
      along with mechanical robustness have gained immense attraction due to the
      substantial advancements and rampant requirements of storage devices. To meet the
      exponentially growing demand of microsized energy storage device, a cost
      effective and durable supercapacitor is mandatory to realize their practical
      applications. Here, in this work, the fabrication route of novel electrode
      materials with high flexibility and charge-storage capability is reported using
      the hybrid structure of 1D zinc oxide (ZnO) nanorods and conductive
      polyvinylidene fluoride-tetrafluoroethylene (P(VDF-TrFE)) electrospun nanofibers.
      The ZnO nanorods are conformably grown on conductive P(VDF-TrFE) nanofibers to
      fabricate the light-weighted porous electrodes for supercapacitors. The
      conductive nanofibers acts as a high surface area scaffold with significant
      electrochemical performance, while the addition of ZnO nanorods further enhances
      the specific capacitance by 59%. The symmetric cell with the fabricated
      electrodes presents high areal capacitance of 1.22 mF cm-2 at a current density
      of 0.1 mA cm-2 with a power density of more than 1600 W kg-1 . Furthermore, these
      electrodes show outstanding flexibility and high stability with 96% and 78%
      retention in specific capacitance after 1000 and 5000 cycles, respectively. The
      notable mechanical durability and robustness of the cell acquire both good
      flexibility and high performance.

PMID- 29045045
TI  - Mesenchymal Stromal Cell Therapy in Bronchopulmonary Dysplasia: Systematic Review
      and Meta-Analysis of Preclinical Studies.
AB  - Extreme prematurity is the leading cause of death among children under 5 years of
      age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the
      most common complication of extreme prematurity. Experimental studies in animal
      models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective.
      To date, no systematic review and meta-analysis has evaluated the preclinical
      evidence of this promising therapy. Our protocol was registered with
      Collaborative Approach to Meta-Analysis and Review of Animal Data from
      Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase
      (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990
      to present) for controlled comparative studies of neonatal animal models that
      received MSCs or cell free MSC-derived conditioned media (MSC-CM). Lung
      alveolarization was the primary outcome. We used random effects models for data
      analysis and followed the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses reporting guidelines. We screened 990 citations; 25 met inclusion
      criteria. All used hyperoxia-exposed neonatal rodents to model BPD. MSCs
      significantly improved alveolarization (Standardized mean difference of -1.330,
      95% confidence interval [CI -1.724, -0.94, I2 69%]), irrespective of timing of
      treatment, source, dose, or route of administration. MSCs also significantly
      ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis,
      and apoptosis. Similarly, MSC-CM significantly improved alveolarization,
      angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in
      hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear
      risk of bias and incomplete reporting in the primary studies highlights
      nonadherence to reporting standards. Overall, safety and efficacy in other
      species/large animal models may provide useful information for guiding the design
      of clinical trials. Stem Cells Translational Medicine 2017;6:2079-2093.

PMID- 29045046
TI  - A novel mouse Cre-driver line targeting Perilipin 2-expressing cells in the
      neonatal lung.
AB  - Pulmonary diseases such as chronic obstructive pulmonary disease, lung fibrosis,
      and bronchopulmonary dysplasia are characterized by the destruction or
      malformation of the alveolar regions of the lung. The underlying pathomechanisms
      at play are an area of intense interest since these mechanisms may reveal
      pathways suitable for interventions to drive reparative processes. Lipid-laden
      fibroblasts (lipofibroblasts) express the Perilipin 2 (Plin2) gene-product,
      PLIN2, commonly called adipose-differentiation related protein (ADRP). These
      cells are also thought to play a role in alveolarization and repair after injury
      to the alveolus. Progress in defining the functional contribution of
      lipofibroblasts to alveolar generation and repair is hampered by a lack of in
      vivo tools. The present study reports the generation of an inducible mouse Cre
      driver line to target cells of the ADRP lineage. Robust Cre-mediated
      recombination in this mouse line was detected in mesenchymal cells of the
      postnatal lung, and in additional organs including the heart, liver, and spleen.
      The generation and validation of this valuable new tool to genetically target,
      manipulate, and trace cells of the ADRP lineage is critical for assessing the
      functional contribution of lipofibroblasts to lung development and repair.

PMID- 29045047
TI  - Star Fruit Intoxication in a Patient Undergoing Regular Hemodialysis.

PMID- 29045048
TI  - Relationship of circulating spexin with markers of cardiovascular disease: a
      pilot study in adolescents with obesity.
AB  - PURPOSE: Spexin, a novel peptide, has potential implications in obesity, satiety
      and energy homeostasis. The current study examined the relationship of spexin
      with various biomarkers of cardiovascular disease and endothelial function in
      adolescents with obesity. METHODS: Nineteen adolescents with obesity (age, 15.8
      +/- 1.7 years) were studied. Spexin, leptin and various cardiovascular disease
      biomarkers were measured. Endothelial function was assessed by high-resolution
      Doppler ultrasonography of the right brachial artery. RESULTS: Spexin
      concentration (median [interquartile range] 0.38 ng/mL [0.29-0.59 ng/mL]) was
      inversely correlated (r = -0.50, P = 0.03) with leptin. When participants were
      clustered into two groups ('high spexin and low leptin' vs. 'low spexin and high
      leptin'), the odds of having 'low spexin and high leptin' in participants with
      higher hs-CRP (>= 3 mg/L) were 12.25 times (95 per cent CI -1 to139, P = 0.026)
      higher than those of participants with lower hs-CRP (<3 mg/L). Spexin levels,
      however, were not associated with measures of endothelial function. CONCLUSIONS:
      The inverse association between spexin and leptin and the presence of higher
      concentrations of hs-CRP in adolescents with obesity in the setting of 'low
      spexin and high leptin' suggest a potential role for spexin in the regulation of
      satiety and certain cardiovascular risk factors in children with obesity.

PMID- 29045049
TI  - Germinal Center B Cells Are Essential for Collagen-Induced Arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is considered to be a prototypical
      autoimmune disorder. Several mechanisms have been proposed for the known
      pathologic function of B cells in RA, including antigen presentation, cytokine
      secretion, and humoral immunity. The aim of this study was to address the
      function of B lymphocytes in experimental arthritis. METHODS: We mapped the
      adaptive immune response following collagen-induced arthritis (CIA). We
      subsequently monitored these responses and disease outcomes in genetically
      modified mouse strains that lack mature B cell or germinal center (GC)
      functionality in a B cell-intrinsic manner. RESULTS: Following primary
      immunization, the draining lymph nodes broadly reacted against type II collagen
      (CII) with the formation of GCs and T cell activation. Mice that lacked mature B
      cell function were fully protected against CIA and had a severely attenuated
      ability to mount isotype-switched humoral immune responses against CII. Almost
      identical results were observed in mice that were selectively deficient in GC
      responses. Importantly, GC-deficient mice were fully susceptible to collagen
      antibody-induced arthritis. CONCLUSION: We identified GC formation and
      anticollagen antibody production as the key pathogenic functions of B cells in
      CIA. The role of B cells in RA is likely to be more complex. However, targeting
      the GC reaction could allow for therapeutic interventions that are more refined
      than general B cell depletion.

PMID- 29045050
TI  - The utility of solid-phase microextraction in evaluating polycyclic aromatic
      hydrocarbon bioavailability during habitat restoration with dredged material at
      moderately contaminated sites.
AB  - The over- or underprediction of risk in moderately contaminated sediments can
      have a large impact on the nature of applied management strategies given that
      concentrations border on being toxic or not toxic. Project managers should give
      significant consideration as to how moderate levels of contaminants in native
      sediments and dredged material used for restoration will impact recovery of
      habitat. Total solid-phase (Ctotal ) and porewater (Cfree ) polycyclic aromatic
      hydrocarbons (PAHs) were quantified in native sediments and dredged material to
      determine if the predictions of risk from Ctotal are consistent with those based
      on Cfree . The sediment matrix phase in which PAHs were quantified resulted in
      disparate conclusions regarding the predicted reduction in contamination
      following restoration. Total solid-phase PAH concentrations suggested a
      significant decrease following restoration, whereas little to no change was
      observed in measured Cfree . Risk metrics based on Ctotal gave inconclusive
      estimates for toxicity, whereas measured Cfree suggested toxicity is unlikely, a
      conclusion consistent with toxicity testing. The incorporation of black carbon
      (BC) into model estimates for Cfree gave predictions more consistent with
      measured Cfree , suggesting that geochemical conditions (especially BC) play an
      important part in predicting toxicity at moderately contaminated sites. In
      addition to the use of Cfree in toxicity evaluation, in-situ Cfree measurements
      provided a constraint on diffusive PAH loads from sediment relative to ongoing
      stream loads. If passive sampling had been employed during the sampling designs
      and site evaluations, the costs of toxicity testing would not have been incurred,
      given that Cfree suggested little to no toxicity. The results from the project
      highlight the benefits to be gained by moving beyond inconclusive, screening
      level Ctotal metrics and implementing more sensitive and accurate Cfree metrics
      in assessments of risk in moderately contaminated sediments. Integr Environ
      Assess Manag 2018;14:212-223. (c) 2017 SETAC.

PMID- 29045052
TI  - A review of wheat diseases-a field perspective.
AB  - Wheat is one of the primary staple foods throughout the planet. Significant yield
      gains in wheat production over the past 40 years have resulted in a steady
      balance of supply versus demand. However, predicted global population growth
      rates and dietary changes mean that substantial yield gains over the next several
      decades will be needed to meet this escalating demand. A key component to meeting
      this challenge is better management of fungal incited diseases, which can be
      responsible for 15%-20% yield losses per annum. Prominent diseases of wheat that
      currently contribute to these losses include the rusts, blotches and head
      blight/scab. Other recently emerged or relatively unnoticed diseases, such as
      wheat blast and spot blotch, respectively, also threaten grain production. This
      review seeks to provide an overview of the impact, distribution and management
      strategies of these diseases. In addition, the biology of the pathogens and the
      molecular basis of their interaction with wheat are discussed.

PMID- 29045051
TI  - Minimum Performance on Clinical Tests of Physical Function to Predict Walking
      6,000 Steps/Day in Knee Osteoarthritis: An Observational Study.
AB  - OBJECTIVE: Evidence of physical function difficulties, such as difficulty rising
      from a chair, may limit daily walking for people with knee osteoarthritis (OA).
      The purpose of this study was to identify minimum performance thresholds on
      clinical tests of physical function predictive to walking >=6,000 steps/day. This
      benchmark is known to discriminate people with knee OA who develop functional
      limitation over time from those who do not. METHODS: Using data from the
      Osteoarthritis Initiative, we quantified daily walking as average steps/day from
      an accelerometer (Actigraph GT1M) worn for >=10 hours/day over 1 week. Physical
      function was quantified using 3 performance-based clinical tests: 5 times sit-to
      stand test, walking speed (tested over 20 meters), and 400-meter walk test. To
      identify minimum performance thresholds for daily walking, we calculated physical
      function values corresponding to high specificity (80-95%) to predict walking
      >=6,000 steps/day. RESULTS: Among 1,925 participants (mean +/- SD age 65.1 +/-
      9.1 years, mean +/- SD body mass index 28.4 +/- 4.8 kg/m2 , and 55% female) with
      valid accelerometer data, 54.9% walked >=6,000 steps/day. High specificity
      thresholds of physical function for walking >=6,000 steps/day ranged 11.4-14.0
      seconds on the 5 times sit-to-stand test, 1.13-1.26 meters/second for walking
      speed, or 315-349 seconds on the 400-meter walk test. CONCLUSION: Not meeting
      these minimum performance thresholds on clinical tests of physical function may
      indicate inadequate physical ability to walk >=6,000 steps/day for people with
      knee OA. Rehabilitation may be indicated to address underlying impairments
      limiting physical function.

PMID- 29045053
TI  - Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new
      inhibitors of the Leishmania mexicana cysteine protease CPB2.8DeltaCTE.
AB  - In an effort to identify novel molecular warheads able to inhibit Leishmania
      mexicana cysteine protease CPB2.8DeltaCTE, fused benzo[b]thiophenes and
      beta,beta'-triketones emerged as covalent inhibitors binding the active site
      cysteine residue. Enzymatic screening showed a moderate-to-excellent activity
      (12%-90% inhibition of the target enzyme at 20 MUm). The most promising compounds
      were selected for further profiling including in vitro cell-based assays and
      docking studies. Computational data suggest that benzo[b]thiophenes act
      immediately as non-covalent inhibitors and then as irreversible covalent
      inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'
      triketones with a Y-topology. Based on the predicted physicochemical and ADME-Tox
      properties, compound 2b has been identified as a new drug-like, non-mutagen, non
      carcinogen, and non-neurotoxic lead candidate.

PMID- 29045056
TI  - Role modelling: moving from implicit to explicit.

PMID- 29045055
TI  - C2-Modified Sparteine Derivatives Are a New Class of Potentially Long-Acting
      Sodium Channel Blockers.
AB  - The lupin alkaloid sparteine is a well-known chiral diamine with a range of
      applications in asymmetric synthesis, as well as a blocker of voltage-gated
      sodium channels (VGSCs). However, there is only scarce information on the VGSC
      blocking activity of sparteine derivatives where the structure of the parent
      alkaloid is retained. Building on the recent renewed availability of sparteine
      and derivatives we report herein how modification of sparteine at position 2
      produces irreversible blockers of VGSCs. These compounds could be clinically
      envisaged as long-lasting local anesthetics.

PMID- 29045054
TI  - Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's
      disease.
AB  - The identification of novel genetic modifiers of age-at-onset (AAO) of
      Alzheimer's disease (AD) could advance our understanding of AD and provide novel
      therapeutic targets. A previous genome scan for modifiers of AAO among families
      affected by early-onset AD caused by the PSEN2 N141I variant identified 2 loci
      with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the
      fine-mapping of these 2 linkage regions, and test for replication in 6
      independent datasets. By fine-mapping these linkage signals in a single large
      family, we reduced the linkage regions to 11% their original size and nominated
      54 candidate variants. Among the 11 variants associated with AAO of AD in a
      larger sample of Germans from Russia, the strongest evidence implicated promoter
      variants influencing NCSTN on 1q23.3 and ZBTB4 on 17p13.2. The association
      between ZBTB4 and AAO of AD was replicated by multiple variants in independent,
      trans-ethnic datasets. Our results show association between AAO of AD and both
      ZBTB4 and NCSTN. ZBTB4 is a transcriptional repressor that regulates the cell
      cycle, including the apoptotic response to amyloid beta, while NCSTN is part of
      the gamma secretase complex, known to influence amyloid beta production. These
      genes therefore suggest important roles for amyloid beta and cell cycle pathways
      in AAO of AD.

PMID- 29045057
TI  - Proper training in laparoscopic hernia repair is necessary to minimize the rising
      recurrence rate in Japan.
AB  - INTRODUCTION: The Japan Society for Endoscopic Surgery reported that the
      recurrence rate for inguinal hernia repair in Japan was less than 1% in 2010.
      However, its 2012 survey found that the recurrence rate had increased to 4% for
      the transabdominal preperitoneal procedure and 5% for the totally extraperitoneal
      procedure. We held 14 hernia repair training courses from 2011 to 2016 with help
      from Covidien. This study aimed to determine the effect of this training on the
      recurrence rate. METHODS: Training was composed of a theoretical revision of
      inguinal anatomy, dry laboratory suturing, a video lecture, and practice on an
      animal model. We made inquiries about the length of each surgeon's career, post
      training changes in surgical methods, and recurrence rates before and after
      training. RESULTS: We received responses from 159 of 300 trainees (53%). The mean
      career length was 12.7 +/- 8.2 years. The annual number of transabdominal
      preperitoneal procedures performed increased from 20.9 +/- 29.9 to 32.4 +/- 56.1
      after training (P < 0.001), and the number of totally extraperitoneal procedures
      increased from 9.5 +/- 13.9 to 13.9 +/- 16.9 (P = 0.0218). The annual number of
      procedures performed via the anterior approach decreased from 153.1 +/- 28.4 to
      28.4 +/- 52.2 after training (P < 0.001). The pre-training transabdominal
      preperitoneal procedure recurrence rate was 0.9%, and this decreased to 0.4%
      after training. There was no pre-training recurrence rate for the totally
      extraperitoneal procedure, but this was 0.4% after training. CONCLUSION: The high
      recurrence rate after inguinal hernia repair in Japan was mainly due to
      inadequate training in the laparoscopic method. Our laparoscopic hernia repair
      training course achieved low recurrence rates.

PMID- 29045058
TI  - Loop-mediated isothermal amplification (LAMP) as an alternative to PCR: A rapid
      on-site detection of gene doping.
AB  - Innovation in medical research has been diverted at multiple occasions to enhance
      human performance. The predicted great progress in gene therapy has raised some
      concerns regarding its misuse in the world of sports (gene doping) for several
      years now. Even though there is no evidence that gene doping has ever been used
      in sports, the continuous improvement of gene therapy techniques increases the
      likelihood of abuse. Therefore, since 2004, efforts have been invested by the
      anti-doping community and WADA for the development of detection methods. Several
      nested PCR and qPCR-based strategies exploiting the absence of introns in the
      transgenic DNA have been proposed for the long-term detection of transgene in
      blood. Despite their great sensitivity, those protocols are hampered by
      limitations of the techniques that can be cumbersome and costly. The purpose of
      this perspective is to describe a new approach based on loop-mediated isothermal
      amplification (LAMP) for the detection of gene doping. This protocol enables a
      rapid and simple method to amplify nucleic acids with a high sensitivity and
      specificity and with a simple visual detection of the results. LAMP is already
      being used in clinical application for the detection of viruses or mutations.
      Therefore, this technique has the potential to be further developed for the
      detection of foreign genetic material in elite athletes. Copyright (c) 2017 John
      Wiley & Sons, Ltd.

PMID- 29045059
TI  - Comparative study of cylindrical and parallel-plate electrophoretic separations
      for the removal of ions and sub-23 nm particles.
AB  - Cylindrical and parallel-plate electrophoretic separations for the removal of
      ions and sub-23 nm particles were compared in this study. First, COMSOL
      Multiphysics(r) software was utilized to simulate the ion and particle
      trajectories inside both electrophoretic separations. The results show that ions
      and sub-23 nm particles are removed simultaneously and that all particles can
      pass through both electrophoretic separations smoothly at a trap voltage of 25 V.
      The experimental results show that ion losses become smaller with increasing ion
      flow rates, and ion losses of the cylindrical and parallel-plate electrophoretic
      separations range from 56.2 to 71.6% and from 43.8 to 59.6%, respectively, at ion
      flow rates ranging from 1-3 L/min. For the removal of ions and sub-23 nm
      particles, the collection efficiency of both electrophoretic separations can
      reach 100%, but the parallel-plate electrophoretic separation requires a lower
      trap voltage. The particle loss of the parallel-plate electrophoretic separation
      is under approximately 10%, which is lower than that of the cylindrical
      electrophoretic separation. In particular, for large particles (800-2500 nm), the
      particle losses inside the cylindrical electrophoretic separation are
      approximately two times higher than those inside the parallel-plate
      electrophoretic separation. The parallel-plate electrophoretic separation is
      beneficial for the removal of ions and sub-23 nm particles.

PMID- 29045060
TI  - Competency assessment form to improve feedback.
AB  - BACKGROUND: In-training evaluation reports are a commonly used assessment method
      for clinical learners that can characterise the development of competence in
      essential domains of practice. Strategies to increase the usefulness and
      specificity of written narrative comments about learner performance in these
      reports are needed to guide their learning. Soliciting narrative comments by
      competency domain from supervising doctors on in-training evaluation reports
      could improve the quality of written feedback to students. METHODS: This is a pre
      post study examining narrative comments derived from assessments of core
      clerkship students by faculty members and resident supervisors in seven
      clerkships using two assessment forms in academic years 2013/14 (pre; two
      comments fields - summative, constructive) and 2014/15 (post; seven comments
      fields - six competency domains, constructive comments). Using a purposive sample
      of 60 students based on overall clerkship performance, we conducted content
      analysis of written comments to compare comment quality based on word count,
      competencies addressed and reinforcing or constructive content. Differences
      between the two forms across these three components of quality were compared
      using Student's t-tests. RESULTS: The revised form elicited more narrative
      comments in all seven clerkships, with more competencies addressed. The revised
      form led to a decrease in the proportion of constructive comments about the
      students' performances. In-training evaluation reports are a commonly used
      assessment method for clinical learners DISCUSSION: Structural changes to a
      medical student assessment form to elicit narrative comments by competency
      improved some measures of the quality of narrative comments provided by faculty
      members and residents. Additional study is needed to determine how learners use
      this information to improve their clinical practice.

PMID- 29045061
TI  - Suppression of MAPK signaling in BRAF-activated PTEN-deficient melanoma by
      blocking beta-catenin signaling in cancer-associated fibroblasts.
AB  - Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been
      associated with formation of a dynamic and optimized niche for tumor cells to
      grow and evade cell death induced by therapeutic agents. We recently reported
      that ablation of beta-catenin expression in stromal fibroblasts and CAFs
      disrupted their biological activities in in vitro studies and in an in vivo
      B16F10 mouse melanoma model. Here, we show that the development of a BRAF
      activated PTEN-deficient mouse melanoma was significantly suppressed in vivo
      after blocking beta-catenin signaling in CAFs. Further analysis revealed that
      expression of phospho-Erk1/2 and phospho-Akt was greatly reduced, effectively
      abrogating the activating effects and abnormal cell cycle progression induced by
      Braf and Pten mutations. In addition, the epithelial-mesenchymal transition (EMT)
      like process was also suppressed in melanoma cells. Taken together, our data
      highlight an important crosstalk between CAFs and the RAF-MEK-ERK signaling
      cascade in BRAF-activated melanoma and may offer a new approach to abrogate host
      dependent drug resistance in targeted therapy.

PMID- 29045063
TI  - Evaluating manufacturing process profile comparability with multivariate
      equivalence testing: Case study of cell-culture small scale model transfer.
AB  - This article studies the Generalized Mahalanobis Distance (GMD) approach proposed
      by Hoffelder which measures the dissimilarity of two multivariate Gaussian
      distributions with arbitrary covariance matrices and unequal sample sizes. This
      investigation demonstrated that, with appropriate adjustment, the GMD approach
      can achieve the targeted nominal Type I error and provide sufficient power for
      testing equivalence between two profile populations. The adjusted GMD approach
      was applied to examine the equivalence of harvest profiles between a 12L small
      scale model and 2000L manufacturing scale in a transfer study performed at Sanofi
      Specialty Care Framingham Biologics. The harvest profiles were evaluated based on
      three critical parameters (Productivity, Lactate Production, and Total Cell
      Density) and deemed practically equivalent using a pre-defined equivalence margin
      per the adjusted GMD approach. (c) 2017 American Institute of Chemical Engineers
      Biotechnol. Prog., 34:187-195, 2018.

PMID- 29045062
TI  - Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis.
AB  - We propose a new flowchart for the treatment of acute cholecystitis (AC) in the
      Tokyo Guidelines 2018 (TG18). Grade III AC was not indicated for straightforward
      laparoscopic cholecystectomy (Lap-C). Following analysis of subsequent clinical
      investigations and drawing on Big Data in particular, TG18 proposes that some
      Grade III AC can be treated by Lap-C when performed at advanced centers with
      specialized surgeons experienced in this procedure and for patients that satisfy
      certain strict criteria. For Grade I, TG18 recommends early Lap-C if the patients
      meet the criteria of Charlson comorbidity index (CCI) <=5 and American Society of
      Anesthesiologists physical status classification (ASA-PS) <=2. For Grade II AC,
      if patients meet the criteria of CCI <=5 and ASA-PS <=2, TG18 recommends early
      Lap-C performed by experienced surgeons; and if not, after medical treatment
      and/or gallbladder drainage, Lap-C would be indicated. TG18 proposes that Lap-C
      is indicated in Grade III patients with strict criteria. These are that the
      patients have favorable organ system failure, and negative predictive factors,
      who meet the criteria of CCI <=3 and ASA-PS <=2 and who are being treated at an
      advanced center (where experienced surgeons practice). If the patient is not
      considered suitable for early surgery, TG18 recommends early/urgent biliary
      drainage followed by delayed Lap-C once the patient's overall condition has
      improved. Free full articles and mobile app of TG18 are available at:
      http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical
      questions and references are also included.

PMID- 29045064
TI  - Epidemiology and burden of influenza in the U.S. Department of Veterans Affairs.
AB  - We describe influenza activity in the US Veterans Affairs (VA) population for the
      2010-2011 through 2015-2016 seasons and compare with national CDC FluView data.
      VA confirmed influenza cases ranged from 1005 to 11 506 per season; triage calls
      from 6090 to 10 346; outpatient visits from 3849 to 13 406; antiviral
      prescriptions from 3650 to 32 826; hospitalizations from 546 to 4673; and deaths
      in hospitalized patients from 17 to 139. Peak activity was generally the same as
      observed nationally by the CDC. For the seasons analyzed, correlation between VA
      and CDC %ILI visits (r = .863), influenza hospitalizations (r = .953), positive
      tests (r = .948), and percent of tests positive (r = .938) was strong.
      Understanding influenza burden is important for evaluating prevention priorities
      and resource allocation within VA.

PMID- 29045065
TI  - Direct Coupling of Thermo- and Photocatalysis for Conversion of CO2 -H2 O into
      Fuels.
AB  - Photocatalytic CO2 reduction into renewable hydrocarbon solar fuels is considered
      as a promising strategy to simultaneously address global energy and environmental
      issues. This study focused on the direct coupling of photocatalytic water
      splitting and thermocatalytic hydrogenation of CO2 in the conversion of CO2 -H2 O
      into fuels. Specifically, it was found that direct coupling of thermo- and
      photocatalysis over Au-Ru/TiO2 leads to activity 15 times higher (T=358 K; ca. 99
      % CH4 selectivity) in the conversion of CO2 -H2 O into fuels than that of
      photocatalytic water splitting. This is ascribed to the promoting effect of
      thermocatalytic hydrogenation of CO2 by hydrogen atoms generated in situ by
      photocatalytic water splitting.

PMID- 29045066
TI  - Fatality involving ocfentanil documented by identification of metabolites.
AB  - The use of new psychoactive substances (NPS) has rapidly increased over the last
      decade. In the last 4 years, producers increasingly appear to be targeting non
      controlled synthetic opioids, involving fentanyl derivatives such as ocfentanil
      (OcF). Identification of metabolites is of major importance in the context of NPS
      use, as it could improve the detection window in biological matrices in clinical
      and forensic intoxication cases. Hence, this work aims to report a fatality
      involving OcF documented by the identification of metabolites. A 30-year-old
      woman was found dead at home: an unidentified powder was found near her body and
      some injection sites were found at the autopsy. Toxicological analyses allowed to
      determine the presence of OcF in the powder, blood (3.7/3.9 MUg/L,
      peripheral/cardiac) and in other post-mortem samples. The most relevant potential
      CYP- and UGT-dependent metabolites of OcF were investigated in vitro using human
      liver microsome incubation and liquid chromatography coupled with high resolution
      mass spectrometry, and subsequently confirmed in post-mortem samples. Four OcF
      metabolites were produced in vitro (a mono-hydroxylated OcF, O-desmethylOcF, a
      hydroxylated desmethylOcF and a glucuronidated form of the O-desmethylOcF), and
      all except the glucuronide were observed in blood and bile post-mortem samples.
      Considering the relative intensity of the chromatographic peak areas, O
      desmethylOcF can be suggested to be an abundant metabolite of OcF. Nevertheless,
      the relevance of O-desmethylOcF as being a complementary analytical target of OcF
      for OcF use detection needs further in vivo confirmation, especially through
      analysis of urines from users.

PMID- 29045067
TI  - Reconnectable fiberscopes for chronic in vivo deep-brain imaging.
AB  - Reconnectable bundles consisting of thousands of optical fibers are shown to
      enable high-quality image transmission, offering a platform for the creation of
      implantable fiberscopes for minimally invasive in vivo brain imaging. Experiments
      on various lines of transgenic mice verify the performance of this fiberscope as
      a powerful tool for chronic in vivo neuroimaging using genetically encoded
      calcium indicators, neuronal activity markers as well as axon growth regulators
      and brain-specific protein drivers in deep regions of live brain.

PMID- 29045068
TI  - Coaxial Carbon/MnO2 Hollow Nanofibers as Sulfur Hosts for High-Performance
      Lithium-Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries have recently attracted a large amount of
      attention as promising candidates for next-generation high-power energy storage
      devices because of their high theoretical capacity and energy density. However,
      the shuttle effect of polysulfides and poor conductivity of sulfur are still
      vital issues that constrain their specific capacity and cyclic stability. Here,
      we design coaxial MnO2 -graphitic carbon hollow nanofibers as sulfur hosts for
      high-performance lithium-sulfur batteries. The hollow C/MnO2 coaxial nanofibers
      are synthesized via electrospinning and carbonization of the carbon nanofibers
      (CNFs), followed by an in situ redox reaction to grow MnO2 nanosheets on the
      surface of CNFs. The inner graphitic carbon layer not only maintains intimate
      contact with sulfur and outer MnO2 shell to significantly increase the overall
      electrical conductivity but also acts as a protective layer to prevent
      dissolution of polysulfides. The outer MnO2 nanosheets restrain the shuttle
      effect greatly through chemisorption and redox reaction. Therefore, the robust
      S@C/MnO2 nanofiber cathode delivers an extraordinary rate capability and
      excellent cycling stability with a capacity decay rate of 0.044 and 0.051 % per
      cycle after 1000 cycles at 1.0 C and 2.0 C, respectively. Our present work brings
      forward a new facile and efficient strategy for the functionalization of
      inorganic metal oxide on graphitic carbons as sulfur hosts for high performance
      Li-S batteries.

PMID- 29045071
TI  - On Methods.

PMID- 29045069
TI  - Association of Natural Killer Cell Ligand Polymorphism HLA-C Asn80Lys With the
      Development of Anti-SSA/Ro-Associated Congenital Heart Block.
AB  - OBJECTIVE: Fetal exposure to maternal anti-SSA/Ro antibodies is necessary but not
      sufficient for the development of autoimmune congenital heart block (CHB),
      suggesting that other factors, such as fetal genetic predisposition, are
      important. Given the previously described association between major
      histocompatibility complex alleles and CHB risk, we undertook the present study
      to test the hypothesis that a variant form of HLA-C Asn80Lys, which binds with
      high affinity to an inhibitory killer cell immunoglobulin-like receptor (KIR) and
      thus renders natural killer (NK) cells incapable of restricting inflammation,
      contributes to the development of CHB. METHODS: Members of 192 pedigrees in the
      US and Europe (194 cases of CHB, 91 unaffected siblings, 152 fathers, 167
      mothers) and 1,073 out-of-study controls were genotyped on the Immunochip single
      nucleotide polymorphism microarray. Imputation was used to identify associations
      at HLA-C Asn80Lys (Asn, C1; Lys, C2) and KIR. Tests for association were
      performed using logistic regression. McNemar's test and the pedigree
      disequilibrium test (PDT) were used for matched analyses between affected and
      unaffected children. RESULTS: Compared with out-of-study controls of the same
      sex, the C2 allele was less frequent in the mothers (odds ratio [OR] 0.63, P =
      0.0014) and more frequent in the fathers (OR 1.40, P = 0.0123), yielding a
      significant sex-by-C2 interaction (P = 0.0002). The C2 allele was more frequent
      in affected siblings than in unaffected siblings (OR 3.67, P = 0.0025), which was
      consistent with the PDT results (P = 0.016); these results were observed in both
      sexes and across the US and European cohorts. There was no difference in the
      frequency of the inhibitory KIR genotype (KIR AA) between affected and unaffected
      children (P = 0.55). CONCLUSION: These data establish C2 as a novel genetic risk
      factor associated with CHB. This observation supports a model in which fetuses
      with C2 ligand expression and maternal anti-SSA/Ro positivity may have impaired
      NK cell surveillance, resulting in unchecked cardiac inflammation and scarring.

PMID- 29045073
TI  - Comparison of the Effectiveness of Ultrasound-Guided Steroid Injections and Blind
      Steroid Injections in the Treatment of Carpal Tunnel Syndrome: Comment on the
      Article by Evers et al.

PMID- 29045072
TI  - Cell Signaling Model Connects Vorinostat Pharmacokinetics and Tumor Growth
      Response in Multiple Myeloma Xenografts.
AB  - Multiple myeloma is a fatal hematological malignancy with high rates of drug
      resistance and relapse. Vorinostat, a histone deacetylase inhibitor, has shown
      promise in enhancing efficacy when combined with current myeloma therapies. In
      this study, temporal changes of critical proteins and cell proliferation were
      measured in myeloma cells exposed to vorinostat. A model linking biomarker
      dynamics to cell proliferation was developed that captured vorinostat effects on
      signal transduction and cell viability. The model structure and parameters were
      fixed to describe tumor dynamics in vivo, and tumor-specific growth and death
      rate parameters were estimated. The signaling model captured tumor growth
      inhibition in murine xenografts for a range of dose levels and regimens. This
      model may be used as a mechanistic bridge to link vorinostat exposure to
      molecular events and pharmacodynamic (PD) outcomes. It may also provide a
      translational platform to explore vorinostat activity as a single agent and in
      combination regimens.

PMID- 29045074
TI  - Detection of autologous blood transfusions using a novel dried blood spot method.
AB  - In doping control laboratories, autologous blood transfusions are currently
      detected using an indirect method that monitors changes in an athlete's
      hemoglobin concentration [Hb] and reticulocyte percent (Ret%) over time. The
      method is limited by the need for a phlebotomist to collect venous blood and the
      limited blood stability which requires temperature-controlled shipment and
      analysis within 72 hours. These limitations significantly reduce the number of
      samples collected from each athlete and thus the utility of the method. We have
      recently developed a method to measure immature reticulocytes (IRC) and red blood
      cells (RBC) in dried blood spots, which could replace the current venous blood
      method. In the DBS method, cell-specific proteins are digested with trypsin and
      measured by mass spectrometry. Two proteins, CD71 and Band3, are measured to
      count IRC and RBC, respectively. The method was tested in an autologous
      transfusion study consisting of 15 subjects who received blood and 11 subjects
      who received saline. After transfusion, the average CD71/Band3 ratio in the blood
      group was statistically different from the saline group at days 5, 6, 13, and 20.
      The average CD71/Band3 ratio decreased to a minimum of 61 +/- 8% of baseline,
      while Ret% decreased to 75 +/- 5% of baseline. Based on experimentally defined
      criteria, the CD71/Band3 ratio could detect 7 out of 10 blood transfusion
      subjects, while Ret% could detect 3 out of 10. Thus, the DBS method could improve
      detection of autologous transfusion and allow increased sample collection.

PMID- 29045075
TI  - Immunocytochemistry for SOX-11 and TFE3 as diagnostic markers for solid
      pseudopapillary neoplasms of the pancreas in FNA biopsies.
AB  - BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare
      malignant tumors that can be sampled via endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA). Although diagnosing SPNs can be straightforward in cases
      with a classic morphology and a typical immunoprofile, challenges can occur with
      morphologic variants or limited specimens. Recently, 2 immunohistochemical
      stains, SRY-related high-mobility group box 11 (SOX-11) and transcription factor
      E3 (TFE3), have been demonstrated to be highly sensitive and specific for SPNs in
      pancreatic resection specimens. The current study evaluates the diagnostic
      utility of these stains with EUS-FNA. METHODS: Thirteen EUS-FNA specimens from
      SPNs with sufficient material for immunocytochemistry were identified from 2000
      to 2016. These cases were compared with 13 EUS-FNA specimens of non-SPN
      pancreatic neoplasms. Immunocytochemistry for SOX-11, TFE3, and beta-catenin was
      performed on all cell blocks and then was scored independently by 2 pathologists
      in a masked manner. RESULTS: Nuclear reactivity for SOX-11 was detected in 13 of
      13 SPNs and in 0 of 13 non-SPNs; this resulted in sensitivity and specificity
      values of 100%, a positive predictive value (PPV) of 1, and a negative predictive
      value (NPV) of 1. Nuclear reactivity for TFE3 was detected in 9 of 13 SPNs and in
      0 of 13 non-SPNs; this resulted in a sensitivity of 69.2%, a specificity of 100%,
      a PPV of 1, and an NPV of 0.765. Nuclear reactivity for beta-catenin was detected
      in 13 of 13 SPNs and in 1 of 13 non-SPNs; this resulted in a sensitivity of 100%,
      a specificity of 92.3%, a PPV of 0.929, and an NPV of 1. CONCLUSIONS: SOX-11 is a
      sensitive and specific immunocytochemical stain for SPNs in EUS-FNA specimens,
      and it may be useful as a diagnostic marker for distinguishing SPNs from its
      cytologic mimics. Cancer Cytopathol 2017;125:831-7. (c) 2017 American Cancer
      Society.

PMID- 29045077
TI  - Subjective Complaints as the Main Reason for Biosimilar Discontinuation After
      Open-Label Transition From Reference Infliximab to Biosimilar Infliximab.
AB  - OBJECTIVE: To evaluate drug survival, effectiveness, pharmacokinetics,
      immunogenicity, and safety in daily practice after transitioning treatment from
      original reference infliximab (Remicade [REM]) to a biosimilar infliximab (CT-P13
      [Remsima; Inflectra]) in patients with rheumatoid arthritis, psoriatic arthritis,
      or ankylosing spondylitis. METHODS: Of the initial 222 REM-treated patients, 192
      agreed to transition to CT-P13 and were included in this multicenter prospective
      cohort study. Changes in the Disease Activity Score in 28 joints using the C
      reactive protein level (DAS28-CRP) and the Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI) and changes in the CRP levels, infliximab trough levels,
      and anti-infliximab antibody levels were assessed after 6 months, and adverse
      events (AEs) were documented. Drug survival and prognostic factors were analyzed
      using Kaplan-Meier and Cox regression analyses. RESULTS: During 6 months follow
      up, 24% of the patients (n = 47) discontinued CT-P13. Thirty-seven patients
      restarted REM, 7 switched to another biologic drug, and 3 continued without a
      biologic drug. The DAS28-CRP remained stable from baseline to month 6, with a
      mean +/- SD score of 2.2 +/- 0.9 at baseline to 2.2 +/- 0.8 at 6 months
      (difference of 0.0 [95% confidence interval (95% CI) -0.1, 0.2]). The BASDAI
      increased from a mean +/- SD of 3.8 +/- 2.0 at baseline to 4.3 +/- 2.1 at 6
      months (difference of +0.5 [95% CI 0.1, 0.9]). The CRP levels, infliximab trough
      levels, and anti-infliximab antibody levels did not change. Just prior to CT-P13
      discontinuation, the DAS28-CRP components tender joint count and patient's global
      assessment of disease activity, as well as the BASDAI were increased compared to
      baseline. The most frequently reported AEs were arthralgia, fatigue, pruritus,
      and myalgia. A shorter REM infusion interval (hazard ratio: 0.77 [95% CI 0.62,
      0.95]) at baseline was predictive of discontinuing CT-P13. CONCLUSION: In our
      cohort, one-fourth of patients discontinued CT-P13 during 6 months of follow-up,
      mainly due to an increase in the subjective features of the tender joint count
      and the patient's global assessment of disease activity and/or subjective AEs,
      possibly explained by nocebo effects and/or incorrect causal attribution effects.

PMID- 29045076
TI  - Outside-in HLA class I signaling regulates ICAM-1 clustering and endothelial cell
      monocyte interactions via mTOR in transplant antibody-mediated rejection.
AB  - Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy
      (TAV) is the major obstacle for long-term survival of solid organ transplants.
      AMR is caused by donor-specific antibodies to HLA, which contribute to TAV by
      initiating outside-in signaling transduction pathways that elicit monocyte
      recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR)
      inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic
      underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell
      activation and monocyte recruitment. We used an in vitro model to assess monocyte
      binding to HLA I Ab-activated endothelial cells and found mTOR inhibition reduced
      ezrin/radixin/moesin (ERM) phosphorylation, intercellular adhesion molecule 1
      (ICAM-1) clustering, and monocyte firm adhesion to HLA I Ab-activated
      endothelium. Further, in a mouse model of AMR, in which C57BL/6. RAG1-/-
      recipients of BALB/c cardiac allografts were passively transferred with donor
      specific MHC I antibodies, mTOR inhibition significantly reduced vascular injury,
      ERM phosphorylation, and macrophage infiltration of the allograft. Taken
      together, these studies indicate mTOR inhibition suppresses ERM phosphorylation
      in endothelial cells, which impedes ICAM-1 clustering in response to HLA class I
      Ab and prevents macrophage infiltration into cardiac allografts. These findings
      indicate a novel therapeutic application for mTOR inhibitors to disrupt
      endothelial cell-monocyte interactions during AMR.

PMID- 29045078
TI  - Skin tears and risk factors assessment: a systematic review on evidence-based
      medicine.
AB  - Skin tears represent a common condition of traumatic wounds, which may be
      encountered in some categories of individuals at the extremes of age, such as
      infants and the elderly. Despite the high prevalence and cost of these lesions,
      there has been little investigation into the risk factors that lead to this
      condition. The aim of this review was to systematically evaluate the main risk
      factors involved in development of skin tears. We planned to include all the
      studies dealing with risk factors related to skin tears. Only publications in
      English were considered. We excluded all the studies that did not properly fit
      our research question and those with insufficient data. Of the 166 records found,
      24 matched our inclusion criteria. After reading the full-text articles, we
      decided to exclude seven articles because of the following reasons: (1) not
      responding properly to our research questions and (2) insufficient data; the
      final set included 17 articles. From a literature search, we found the following
      main issues related to risk factors, which have been described in detail in this
      section: age-related skin changes, dehydration, malnutrition, sensory changes,
      mobility impairment, pharmacological therapies and mechanical factors related to
      skin care practices. Our findings clearly show that in frail populations
      (especially infant and elderly), the stratification risk, as a primary prevention
      strategy, is an effective tool in avoiding the development of chronic wounds. The
      development and the implementation of prevention strategies based on appropriate
      knowledge of the risk factors involved and the adoption of correct techniques
      during skin care practices could reduce or even avoid the onset of skin tears.

PMID- 29045079
TI  - Improvements in health-related quality of life over 3 years with liraglutide 3.0
      mg compared with placebo in participants with overweight or obesity.
AB  - Previously in the SCALE Obesity and Prediabetes trial, at 1 year, participants
      with obesity (or overweight with comorbidities) and prediabetes receiving
      liraglutide 3.0 mg experienced greater improvements in health-related quality of
      life (HRQoL) than those receiving placebo. The current study extends these
      findings by examining 3-year changes in HRQoL. HRQoL was assessed using the
      obesity-specific Impact of Weight on Quality of Life-Lite (IWQOL-Lite)
      questionnaire, as well as the Short-Form 36 v2 (SF-36) health survey. At 3 years,
      mean change (+/-standard deviation) in IWQOL-Lite total score from baseline for
      liraglutide (n = 1472) was 11.0 +/- 14.2, vs. 8.1 +/- 14.7 for placebo (n = 738)
      (estimated treatment difference [ETD] 3.4 [95% confidence interval (CI): 2.0,
      4.7], P < 0.0001). Mean change in SF-36 physical component summary (PCS) score
      from baseline for liraglutide was 3.1 +/- 7.3, vs. 2.6 +/- 7.6 for placebo (ETD
      0.87 [95% CI: 0.17, 1.6], P = 0.0156). Mean change in SF-36 mental component
      summary score did not significantly differ between groups. Both IWQOL-Lite total
      score and PCS score demonstrated an association between greater HRQoL improvement
      with higher weight loss. Liraglutide 3.0 mg was also associated with improved
      health utility (Short-Form-6D and EuroQol-5D, mapped from IWQOL-Lite and/or SF
      36) vs. placebo. Liraglutide 3.0 mg, plus diet and exercise, is associated with
      long-term improvements in HRQoL with obesity or overweight with comorbidity vs.
      placebo.

PMID- 29045081
TI  - Chasing bubbles for cancer diagnostics: Cancer researchers are pursuing membrane
      bound microbubbles and exosomes as new diagnostic tools.

PMID- 29045082
TI  - A Lesson in Trust.

PMID- 29045083
TI  - Hawks and Doves.

PMID- 29045084
TI  - New Approach to Treat and Prevent Oral Disease.

PMID- 29045080
TI  - A Systematic Review of Calorie Labeling and Modified Calorie Labeling
      Interventions: Impact on Consumer and Restaurant Behavior.
AB  - OBJECTIVE: Evidence on the effects of restaurant calorie labeling on consumer and
      restaurant behavior is mixed. This paper examined: (1) consumer responses to
      calorie information alone or compared to modified calorie information and (2)
      changes in restaurant offerings following or in advance of menu labeling
      implementation. METHODS: Searches were conducted in PubMed, Web of Science,
      Policy File, and PAIS International to identify restaurant calorie labeling
      studies through October 1, 2016, that measured calories ordered, consumed, or
      available for purchase on restaurant menus. The reference lists of calorie
      labeling articles were also searched. RESULTS: Fifty-three studies were included:
      18 in real-world restaurants, 9 in cafeterias, and 21 in laboratory or simulation
      settings. Five examined restaurant offerings. CONCLUSIONS: Because of a lack of
      well-powered studies with strong designs, the degree to which menu labeling
      encourages lower-calorie purchases and whether that translates to a healthier
      population are unclear. Although there is limited evidence that menu labeling
      affects calories purchased at fast-food restaurants, some evidence demonstrates
      that it lowers calories purchased at certain types of restaurants and in
      cafeteria settings. The limited data on modified calorie labels find that such
      labels can encourage lower-calorie purchases but may not differ in effects
      relative to calorie labels alone.

PMID- 29045085
TI  - Children of Hawaii Suffer From Highest Rate of Caries.

PMID- 29045086
TI  - Surgery Recommendation Method Established for Craniosynostosis.

PMID- 29045087
TI  - 100 Million Opioids Not Utilized by Patients Following Removal of Third Molars.

PMID- 29045088
TI  - Orofacial Pain Overview: Getting Rid of the Riddles.
AB  - While most pains that find their way to the dental office are dental inorigin,
      some have less familiar roots: muscular, joint, neurological, headache, sinusor
      psychological. All of these roots can at times masquerade as a toothache.
      Thepurpose of this article is to alert the dentist to the select features of each
      root thatdistinguish it from the rest, resulting in efficient and appropriate
      treatment.

PMID- 29045089
TI  - An Osteoblastoma of the Mandible: A Case Study.
AB  - This case study involves a 22-year-old male who experiencedmoderate pain in the
      left side of the mandible for two months. He was diagnosedwith an osteoblastoma
      and treated with local excision, curettage and extractionof the involved teeth.
      Radiographic follow-up indicated that the site healed well.Clinical, radiographic
      and histopathologic features are discussed. Osteoblastomarequires
      interdisciplinary care and should be considered in the differential diagnosisof
      mixed-density lesions detected in the jaws.

PMID- 29045091
TI  - The Dentist's Role in the Multidisciplinary Treatment of Helicobacter pylori
      Infection.

PMID- 29045090
TI  - Do growth hormone and insulin-like growth factor 1 affect prognosis in patients
      with killip I and II class acute myocardial infarction?
AB  - We investigated concentrations and roles of insulin-like growth factor 1 (IGF
      1)and its binding protein (IGF1BP-3), growth hormone (GH), insulin, and markers
      of insulin resistanceand inflammation in acute myocardial infarction (AMI). We
      aimed to assess any possible associationbetween serum GH/IGF-1 axis following AMI
      and short-term survival rates. A follow upstudy was performed in 2010. Study
      group consisted of 75 patients with Killip I and II class AMI.There were 30
      control subjects. Blood samples were obtained within 24 hours of admission and
      analyzedfor the aforementioned hormones. Patients were followed-up during 6
      months for new cardiacevents. Median GH was higher in AMI (0.96; range 0.6-2.4)
      than in controls (0.26; p<0.001). IGF-1was significantly lower in AMI (123 vs.
      132; p<0.05), and so was the IGF-1/GH ratio (p<0.001) andIGF1BP-3. Insulin was
      higher in study group, but without statistical significance. However, we
      foundsignificant between-group differences in other markers of insulin resistance
      (HbA1c, glycemia,HOMA-IR) and inflammation. Simple linear correlation showed
      positive correlation between GHand C-reactive protein. All patients with new
      cardiac events had IGF-1 below median and lower leftventricular ejection
      fraction. In conclusion, IGF-1 may affect outcome of AMI. GH resistance mightbe a
      result of inflammatory/immune response and therefore it could be a useful
      prognostic marker.

PMID- 29045092
TI  - Prepping Your Practice for the Holidays.

PMID- 29045093
TI  - Changes of Drusen Number and Central Retinal Thickness in Age-Related Macular
      Degeneration Patients Over Two Years
AB  - Age-related macular degeneration (ARMD) is the leading cause of blindness in
      developed world but there are still much unknown facts about the disease itself.
      Age, genetic factors and smoking are the three main risk factors for the
      development of ARMD, but the exact pathophysiologicalmechanism of the disease
      remains unknown. Current high resolution optical coherence tomography devices
      provide ample new information on retinal layers, drusen characteristics and their
      interaction. In this study, we analyzed 44 eyes with drusiform dry ARMD using
      high resolution opticalcoherence tomography over a 2-year period. Our results
      showed a statistically significant increase in drusen number in both females and
      males in the 2-year period. On average, increment by 4 and 5 drusen per eye
      during the 2-year period was recorded in female and male patients with drusiform
      dryARMD, respectively. Also, statistical analysis of the central retinal
      thickness showed that women with drusiform dry ARMD had a statistically
      significantly thinner macula than their male counterparts.

PMID- 29045094
TI  - Ventilator-Associated Pneumonia: Comparing Cadaveric Liver Transplant and Non
      Transplant Surgical Patients
AB  - Ventilator-associated pneumonia is a frequent complication in intensive care
      surgical patients, particularly those with high severity scores on admission. We
      studied the incidence and clinical outcome of ventilator-associated pneumonia
      among patients undergoing major general surgeryprocedures and those undergoing
      cadaveric liver transplantation in our hospital. Patients with the intensive care
      unit stay longer than four days having undergone surgery or transplantation and
      mechanically ventilated for more than 48 hours were included in the study.
      Ventilator-associated pneumoniadiagnosis was based on a combination of
      radiological signs (progressive infiltrate on chest radiograph), clinical signs
      (fever >38.3  degrees C, leukocytes >12*10(9)/mL) and microbiological data
      (positive culture from tracheal aspiration >10(5) or bronchoalveolar lavage >104
      colonies/mL). Medical records of1037 patients were reviewed and 157 patients were
      found to have been mechanically ventilated for more than 48 hours: 62
      transplanted and 95 non-transplanted. Only 39 (24.84%) patients matched the
      criteria for ventilator-associated pneumonia. There were no differences in sex,
      age, duration ofmechanical ventilation, length of stay or outcome between the two
      groups. However, the main difference was the mean severity score on admission
      (Simplified Acute Physiology Score II) which was higher among non-transplant
      patients (42+/-16 vs. 31+/-9; p=0.03). Gram-negative bacteria were theleading
      causative agents (82.03%) and were multidrug-resistant. In the intensive care
      surgical population, transplantation per se does not seem to increase patient
      risk for either ventilator-associated pneumonia acquisition or worse outcomes.

PMID- 29045096
TI  - Amalgam Waste Best Management Practices

PMID- 29045098
TI  - Tech Trends. A look into the latest dental and general technology on the market.

PMID- 29045097
TI  - Management of airway obstruction and stridor in pediatric patients
AB  - Stridor is a result of turbulent air-flow through the trachea from upper airway
      obstruction, and although in children it is often due to croup, it can also be
      caused by noninfectious and/or congenital conditions as well as life-threatening
      etiologies. The history and physical examination guide initial management, which
      includes reduction of airway inflammation, treatment of bacterial infection, and,
      less often, imaging, emergent airway stabilization, or surgical management. This
      issue discusses the most common as well as the life-threatening etiologies of
      acute and chronic stridor and its management in the emergency department.

PMID- 29045099
TI  - How to Improve Patient Safety Culture in Croatian Hospitals?
AB  - Patient safety culture (PCS) has a crucial impact on the safety practices of
      healthcare delivery systems. The purpose of this study was to assess the state of
      PSC in Croatian hospitals and compare it with hospitals in the United States. The
      study was conducted in three public generalhospitals in Croatia using the
      Croatian translation of the Hospital Survey of Patient Safety Culture (HSOPSC). A
      comparison of the results from Croatian and American hospitals was performed
      using a T-square test. We found statistically significant differences in all 12
      PSC dimensions. Croatianresponses were more positive in the two dimensions of
      Handoff s and Transitions and Overall Perceptions of Patient Safety. In the
      remaining ten dimensions, Croatian responses were less positive than in US
      hospitals, with the most prominent areas being Nonpunitive Response to Error,
      Frequency ofEvents Reported, Communication Openness, Teamwork within Units,
      Feedback & Communication about Error, Management Support for Patient Safety, and
      Staffing. Our findings show that PSC is significantly lower in Croatian than in
      American hospitals, particularly in the areas of NonpunitiveResponse to Error,
      Leadership, Teamwork, Communication Openness and Staffing. This suggests that a
      more comprehensive system for the improvement of patient safety within the
      framework of the Croatian healthcare system needs to be developed. Our findings
      also help confirm that HSOPSC is auseful and appropriate tool for the assessment
      of PSC. HSOPSC highlights the PSC components in need of improvement and should be
      considered for use in national and international benchmarking.

PMID- 29045100
TI  - Influence of Gap Shape on Biomechanical Properties of Extra-Articular Distal
      Humeral Fracture - A Finite Element Study
AB  - The aim of the study was to assess the influence of gap shape on
      biomechanicalresults in extra-articular distal humeral fracture: with contact on
      the posterior part (by anterior gap)and contact on ulnar column (by radial gap).
      The goal was to examine if and to what extent diddisplacements decrease in
      comparison with previously examined parallel gap without bony contact.The finite
      element analysis on the three different plate constructs was performed, i.e.
      parallel, perpendicularand newly designed Y shape plate were considered.
      Displacements were measured on articularsurface and gap point. The most visible
      decrease of maximum displacements in the distal part of themodel was detected in
      the Y plate model with axial loading: in case of anterior gap 58.5% and
      especiallyat radially formed gap 60.9%. Similarly, at axial loading, displacement
      at the analyzed point onfracture gap most significantly decreased in Y plate
      model (by 49.4%) at posterior bony contact. Moreover,the latter showed
      displacement decrease by 68.5% at ulnar bone contact. Furthermore, if a
      longerradial plate than the ulnar one was used, varus stress could have been
      avoided. Study results suggestedthat sufficient stability could be ensured with
      the newly designed Y shape plate.

PMID- 29045101
TI  - Salivary Flow Rate, Oral Yeast Colonization and Dental Status in
      Institutionalized and Non-Institutionalized Elderly
AB  - Elderly people, especially those institutionalized in long-term care facilities,
      are atrisk of various oral diseases. The aim of the study was to determine the
      incidence of hyposalivation andcolonization/oral fungal infection of oral cavity
      with yeasts, as well as dental status in institutionalizedand non
      institutionalized elderly. The study included 280 institutionalized and 61 non
      institutionalizedelderly people. Salivary flow rate, oral colonization with
      yeasts/oral infection and dental statuswere assessed and compared between the
      groups. The institutionalized elderly had a significantlylower salivary flow rate
      (p=0.035). Oral colonization with yeasts was more frequently found in
      institutionalizedelderly (p<0.001) as compared with non-institutionalized
      elderly. A negative correlationwas found between decreased salivary flow rate and
      oral yeast colonization and oral fungal infectionin both the institutionalized
      (rs=-0.58; p<0.05) and non-institutionalized (rs=-0.52; p<0.05) groups.A
      significant difference in DMFT index was observed between the two groups
      (p<0.001). A negativecorrelation between decreased salivary flow rate and dental
      status was found in both the institutionalized(rs=-0.22; p<0.05) and non
      institutionalized (rs=-0.56; p<0.05) groups. The results revealed asignificantly
      higher level of hyposalivation and oral yeast colonization and poorer dental
      status in theinstitutionalized group as compared with the non-institutionalized
      group of elderly people.

PMID- 29045102
TI  - Comparison of Sleep Disturbances in Post-Traumatic Stress Disorder and Depression
      Patients
AB  - The aim of this study was to explore differences in the intensity of
      depressiveness,sleep disturbances and sleepiness between post-traumatic stress
      disorder (PTSD) patients and patientswith depression. A total of 170 patients
      were examined, including 120 PTSD patients and 50 patientswith depression. All
      participants completed the Beck Depression Inventory, Pittsburgh Sleep
      QualityIndex and Epworth Sleepiness Scale. The results showed difference in the
      subjective assessment ofsleep quality between the war veterans with PTSD and
      civilians with depression, without significantdifferences between them in the
      level of depressiveness and sleepiness. Considering the fact thatinsomnia can
      occur as an early, covert sign of both PTSD and depression and that differences
      in theintensity of sleep disturbances between the groups were established, the
      use of these and similarinstruments for the assessment of sleep quality can be
      useful in distinguishing patients with PTSDand depression, treatment of their
      sleep disturbances, and prevention of more severe symptoms in bothdiagnostic
      categories.

PMID- 29045103
TI  - Sexual Dysfunction and Incidence of Depression in Multiple Sclerosis Patients
AB  - Multiple sclerosis (MS) is one of the most common diseases of the central nervous
      system and usually occurs at the age when people would be expected to be in the
      prime of their sexual lives. In everyday practice, sexual dysfunction is
      underestimated because clinicians mostly concentrateon the classic neurologic
      deficits and often overlook symptoms that can seriously affect the quality of
      life. Our study included 98 patients (42 men and 56 women, mean age 35+/-12
      years) with relapse from our MS register, with established diagnosis of relapsing
      remitting multiple sclerosis accordingto McDonald criteria. Patients completed
      the questionnaires (Sexual Satisfaction Scale, SSS and Beck Depression Scale
      BDS), and underwent neurological assessment (Expanded Disability Status Scale,
      EDSS). All patients were in the group with EDSS 2 to 4 points (mobile patients).
      Therewas no statistically significant difference in BDS and SSS values according
      to EDSS score. Correlation coefficients were calculated (BDS and SSS) for men
      (p=0.42) and women (p=0.44), yielding positive correlation. There was no
      statistically significant difference in BDS and SSS values accordingto gender,
      disease duration or immunomodulatory therapy. In our group of patients, despite
      low EDSS score (fully ambulatory without aid, self sufficient patients) we found
      positive correlation between sexual dysfunction and depression, showing that even
      in such patients the quality of life can bedecreased. In conclusion, sexual
      dysfunction and depression are mostly under-recognized by neurologists because
      they are not part of routine testing; therefore, some additional questionnaires
      should be used in the evaluation in MS patients, even those with low EDSS score,
      in order to improve theirquality of life.

PMID- 29045104
TI  - Incidence of Cardiovascular Risk Factors in Obese Children
AB  - The aim of the study was to determine the prevalence of metabolic syndrome
      factors in obese children by examining blood pressure, lipid status, disorders of
      glycoregulation, and parameters of insulin sensitivity and secretion. The survey
      was conducted as a cross sectional study. Weanalyzed the results of obese
      children aged 7 to 16 years visiting Clinical Centre of Montenegro during the
      2011-2015 period. Out of 173 children with elevated body mass index, 119 (68.8%)
      children were overweight, while first-degree obesity was recorded in 50 (28.9%)
      and second-degreeobesity in four (2.3%) children. High blood pressure was found
      in 35.2%, elevated cholesterol levels in 9.8% and elevated triglyceride levels in
      8.09% of obese children. Oral glucose load testing revealed disturbing fasting
      glycemia in 4.76% and impaired glucose tolerance in 19.04% of obese children.High
      values of insulinemia two hours after glucose load were recorded in 35% of obese
      children. Study results showed the prevalence of risk factors for cardiovascular
      diseases and metabolic disorders, especially carbohydrates and fat, to be very
      high in our population of obese children. This imposes the needof changing
      current mode of assessing dietary habits during general medical examinations, as
      well as to start recording and monitoring overweight children and those with
      pronounced obesity.

PMID- 29045105
TI  - Influence of Fondaparinux Versus Nadroparin Calcium Thromboprophylaxis on
      Clinical Parameters Following Total Knee Arthroplasty
AB  - Fondaparinux has been shown to be as effective as low molecular weight heparinin
      orthopedic surgery, with no cases of heparin induced thrombocytopenia proven
      until today. Themain goal of this prospective randomized controlled trial was to
      define whether thromboprophylaxisin patients with primary osteoarthritis of the
      knee undergoing total knee arthroplasty (TKA) influencesclinical parameters in
      the same manner in patients receiving fondaparinux as in those
      receivingnadroparin during the first 7 postoperative days. Sixty patients with
      primary knee osteoarthritis underwentunilateral TKA performed by the same surgeon
      and were randomized into two groups of 30patients receiving either fondaparinux
      or nadroparin thromboprophylaxis. Patients were comparedaccording to the duration
      of operation, perioperative blood loss, laboratory results and clinical
      evaluationof the edema during the early postoperative period. No differences were
      found between thegroups in the mean duration of surgery, perioperative blood
      loss, and most of laboratory results. Thelevel of urea was significantly lower in
      the nadroparin group on the first and second postoperative day.No cases of
      heparin induced thrombocytopenia, deep vein thrombosis or pulmonary embolism
      werenoted during the study. Study results showed both fondaparinux and nadroparin
      to have the sameinfluence on clinical parameters during the first 7 postoperative
      days in patients undergoing TKA.

PMID- 29045106
TI  - Local Ablative Therapy Options for Patients with Inoperable Pancreatic Cancer:
      Response.

PMID- 29045107
TI  - Do Changing Diagnostic Criteria for Gestational Diabetes Influence Pregnancy
      Outcome?
AB  - The incidence of pregnancy related diabetes has been steadily increasing
      duringthe past decade. The aim of this retrospective study was to evaluate the
      type and prevalence of gestationaldiabetes complications after implementing new
      diagnostic criteria for gestational diabetes. Theincidence of gestational
      diabetes, maternal age, mode of delivery and birth weight were analyzed.Study
      patients were divided into three groups. The first group consisted of patients
      who gave birthduring 2005, the second group during 2011 and the third group
      during 2012. In 2005, the WorldHealth Organization criteria were used on
      diagnosing gestational diabetes, whereas in 2011 and 2012the criteria issued by
      the International Association of Diabetes and Pregnancy Study Groups
      wereconsidered. There was no statistically significant difference among the
      groups according to maternalage, birth weight (p=0.203) and mode of delivery
      (p=0.883). Cesarean section was performed in about30% of deliveries in all groups
      combined. There was no significant difference in the number of
      neonatalhypertrophy (p=0.348), although the distribution of hypertrophy showed a
      tendency towards highervalues in 2005. The incidence of gestational diabetes was
      2.2% in 2005, 6.6% in 2011 and 12% in2012. In conclusion, difference in the
      incidence of pregnancy related diabetes appeared to have resulteddirectly from
      using different diagnostic criteria. The new criteria contributed to a
      relativelyhigher incidence of gestational diabetes but also achieved better
      gestational glycemic control andconsequently better fetal growth regulation.

PMID- 29045108
TI  - Rational Therapy of Urinary Tract Infections in Children in Croatia
AB  - Resistance to chemotherapeutics used in the treatment of urinary tract infection
      isincreasing throughout the world. Taking into account clinical experiences, as
      well as current bacterialresistance in Croatia and neighboring countries, the
      selection of antibiotic should be the optimal one.Treatment of urinary tract
      infection in children is particularly demanding due to their age and
      inclinationto severe systemic reaction and renal scarring. If parenteral
      antibiotics are administered initially,it should be switched to oral medication
      as soon as possible. Financial aspects of antimicrobial therapyare also very
      important with the main goal to seek the optimal cost/benefit ratio. Financial
      orientationmust appreciate the basic primum non nocere as a conditio sine qua non
      postulate as well.

PMID- 29045109
TI  - Measuring Physical Activity in Pregnancy Using Questionnaires: A Meta-Analysis
AB  - Physical activity (PA) during normal pregnancy has various positive effects
      onpregnant women's health. Determination of the relationship between PA and
      health outcomes requiresaccurate measurement of PA in pregnant women. The purpose
      of this review is to provide asummary of valid and reliable PA questionnaires for
      pregnant women. During 2013, Pubmed, OvidSPand Web of Science databases were
      searched for trials on measurement properties of PA questionnairesfor pregnant
      population. Six studies and four questionnaires met the inclusion criteria:
      PregnancyPhysical Activity Questionnaire, Modified Kaiser Physical Activity
      Survey, Short PregnancyLeisure Time Physical Activity Questionnaire and Third
      Pregnancy Infection and Nutrition StudyPhysical Activity Questionnaire.
      Assessment of validity and reliability was performed using correlationsof the
      scores in these questionnaires with objective measures and subjective measures
      (self-report)of PA, as well as test-retest reliability coefficients. Sample sizes
      included in analysis varied from45 to 177 subjects. The best validity and
      reliability characteristics (together with effect sizes) wereidentified for the
      Modified Kaiser Physical Activity Survey and Pregnancy Physical Activity
      Questionnaire(French, Vietnamese, standard). In conclusion, assessment of PA
      during pregnancy remainsa challenging and complex task. Questionnaires are a
      simple and effective, yet limited tool for assessingPA.

PMID- 29045121
TI  - Wafer-Scale Synthesis of Semiconducting SnO Monolayers from Interfacial Oxide
      Layers of Metallic Liquid Tin.
AB  - Atomically thin semiconductors are one of the fastest growing categories in
      materials science due to their promise to enable high-performance electronic and
      optical devices. Furthermore, a host of intriguing phenomena have been reported
      to occur when a semiconductor is confined within two dimensions. However, the
      synthesis of large area atomically thin materials remains as a significant
      technological challenge. Here we report a method that allows harvesting monolayer
      of semiconducting stannous oxide nanosheets (SnO) from the interfacial oxide
      layer of liquid tin. The method takes advantage of van der Waals forces occurring
      between the interfacial oxide layer and a suitable substrate that is brought into
      contact with the molten metal. Due to the liquid state of the metallic precursor,
      the surface oxide sheet can be delaminated with ease and on a large scale. The
      SnO monolayer is determined to feature p-type semiconducting behavior with a
      bandgap of ~4.2 eV. Field effect transistors based on monolayer SnO are
      demonstrated. The synthetic technique is facile, scalable and holds promise for
      creating atomically thin semiconductors at wafer scale.

PMID- 29045122
TI  - A Heat-Resistant and Energetic Metal-Organic Framework Assembled by Chelating
      Ligand.
AB  - Heat-resistant explosives with high performance and insensitivity to external
      stimulus or thermal are indispensable in both the military and civilian worlds
      especially when utilized under harsh conditions. We designed and synthesized a
      new heat-resistant three-dimensional chelating energetic metal-organic framework
      (CEMOF-1) by employing 4-amino-4H-1,2,4-triazole-3,5-diol (ATDO) as a ligand.
      Because of its chelating 3D structural feature, good oxygen balance (-29.58%),
      and high crystal density (2.234 g cm-3), CEMOF-1 demonstrates high decomposition
      temperature (445  degrees C), insensitivity to stimulation, and excellent
      detonation velocity (10.05 km s-1) and detonation pressure (49.36 GPa). The
      advantages of facile synthesis, thermal stability, and powerful explosive
      performance make CEMOF-1 as a promising candidate for heat-resistant explosives
      in future applications.

PMID- 29045123
TI  - Polymyxin B3-Tobramycin Hybrids with Pseudomonas aeruginosa-Selective
      Antibacterial Activity and Strong Potentiation of Rifampicin, Minocycline, and
      Vancomycin.
AB  - There is an urgent need to develop novel antibacterial agents able to eradicate
      drug-resistant Gram-negative pathogens such as Pseudomonas aeruginosa.
      Antimicrobial hybrids have emerged as a promising strategy to combat bacterial
      resistance, as a stand-alone drug but also as an adjuvant in combination with
      existing antibiotics. Herein, we report for the first time the synthesis and
      biological evaluation of polymyxin-aminoglycoside heterodimers composed of
      polymyxin B3 covalently linked to tobramycin via an aliphatic hydrocarbon linker.
      The polymyxin B3-tobramycin hybrids demonstrate potent activity against
      carbapenem-resistant as well as multidrug- or extensively drug-resistant
      (MDR/XDR) P. aeruginosa clinical isolates. Furthermore, the most potent hybrid
      was able to synergize with currently used antibiotics against wild-type and
      MDR/XDR P. aeruginosa but also against Acinetobacter baumannii as well. The
      promising biological activity described herein warrants additional studies into
      design and development of new antimicrobial hybrids able to surmount the problem
      of antimicrobial resistance.

PMID- 29045124
TI  - Effect of the Hydrofluoroether Cosolvent Structure in Acetonitrile-Based Solvate
      Electrolytes on the Li+ Solvation Structure and Li-S Battery Performance.
AB  - We evaluate hydrofluoroether (HFE) cosolvents with varying degrees of
      fluorination in the acetonitrile-based solvate electrolyte to determine the
      effect of the HFE structure on the electrochemical performance of the Li-S
      battery. Solvates or sparingly solvating electrolytes are an interesting
      electrolyte choice for the Li-S battery due to their low polysulfide solubility.
      The solvate electrolyte with a stoichiometric ratio of LiTFSI salt in
      acetonitrile, (MeCN)2-LiTFSI, exhibits limited polysulfide solubility due to the
      high concentration of LiTFSI. We demonstrate that the addition of highly
      fluorinated HFEs to the solvate yields better capacity retention compared to that
      of less fluorinated HFE cosolvents. Raman and NMR spectroscopy coupled with ab
      initio molecular dynamics simulations show that HFEs exhibiting a higher degree
      of fluorination coordinate to Li+ at the expense of MeCN coordination, resulting
      in higher free MeCN content in solution. However, the polysulfide solubility
      remains low, and no crossover of polysulfides from the S cathode to the Li anode
      is observed.

PMID- 29045125
TI  - Polyacrylonitrile Separator for High-Performance Aluminum Batteries with Improved
      Interface Stability.
AB  - Herein we report, for the first time, an overall evaluation of commercially
      available battery separators to be used for aluminum batteries, revealing that
      most of them are not stable in the highly reactive 1-ethyl-3-methylimidazolium
      chloride:aluminum trichloride (EMIMCl:AlCl3) electrolyte conventionally employed
      in rechargeable aluminum batteries. Subsequently, a novel highly stable
      polyacrylonitrile (PAN) separator obtained by the electrospinning technique for
      application in high-performance aluminum batteries has been prepared. The
      developed PAN separator has been fully characterized in terms of morphology,
      thermal stability, and air permeability, revealing its suitability as a separator
      for battery applications. Furthermore, extremely good compatibility and improved
      aluminum interface stability in the highly reactive EMIMCl:AlCl3 electrolyte were
      discovered. The use of the PAN separator strongly affects the aluminum
      dissolution/deposition process, leading to a quite homogeneous deposition
      compared to that of a glass fiber separator. Finally, the applicability of the
      PAN separator has been demonstrated in aluminum/graphite cells. The
      electrochemical tests evidence the full compatibility of the PAN separator in
      aluminum cells. Furthermore, the aluminum/graphite cells employing the PAN
      separator are characterized by a slightly higher delivered capacity compared to
      those employing glass fiber separators, confirming the superior characteristics
      of the PAN separator as a more reliable separator for the emerging aluminum
      battery technology.

PMID- 29045126
TI  - Characterization of Three Druggable Hot-Spots in the Aurora-A/TPX2 Interaction
      Using Biochemical, Biophysical, and Fragment-Based Approaches.
AB  - The mitotic kinase Aurora-A and its partner protein TPX2 (Targeting Protein for
      Xenopus kinesin-like protein 2) are overexpressed in cancers, and it has been
      proposed that they work together as an oncogenic holoenzyme. TPX2 is responsible
      for activating Aurora-A during mitosis, ensuring proper cell division. Disruption
      of the interface with TPX2 is therefore a potential target for novel anticancer
      drugs that exploit the increased sensitivity of cancer cells to mitotic stress.
      Here, we investigate the interface using coprecipitation assays and isothermal
      titration calorimetry to quantify the energetic contribution of individual
      residues of TPX2. Residues Tyr8, Tyr10, Phe16, and Trp34 of TPX2 are shown to be
      crucial for robust complex formation, suggesting that the interaction could be
      abrogated through blocking any of the three pockets on Aurora-A that complement
      these residues. Phosphorylation of Aurora-A on Thr288 is also necessary for high
      affinity binding, and here we identify arginine residues that communicate the
      phosphorylation of Thr288 to the TPX2 binding site. With these findings in mind,
      we conducted a high-throughput X-ray crystallography-based screen of 1255
      fragments against Aurora-A and identified 59 hits. Over three-quarters of these
      hits bound to the pockets described above, both validating our identification of
      hotspots and demonstrating the druggability of this protein-protein interaction.
      Our study exemplifies the potential of high-throughput crystallography facilities
      such as XChem to aid drug discovery. These results will accelerate the
      development of chemical inhibitors of the Aurora-A/TPX2 interaction.

PMID- 29045128
TI  - Radiation Dose Limits for Bioanalytical X-ray Fluorescence Microscopy.
AB  - Analytical approaches that preserve the endogenous state of the examined system
      are essential for the in vivo study of bioinorganics. X-ray fluorescence
      microscopy of biological samples can map elements in vivo at subcellular
      resolutions in tissue samples and multicellular organisms. However, X-ray
      irradiation induces modifications that accumulate with dose. Consequently, the
      utility of X-ray fluorescence microscopy is intrinsically limited by the
      radiation damage it causes and the degree to which it alters the target features
      of interest. Identification of the dose threshold, below which the integrity of
      the specimen and its elemental distribution is preserved, is required to ensure
      valid interpretation of concentrations. Here we use the nematode, Caenorhabditis
      elegans, to explore these issues using three chemical-free specimen preparations:
      lyophilization, cryofixation, and live. We develop quantitative methods for
      investigating damage and present dose limits for each preparation pertaining to
      the micrometer-scale spatial distribution of specific analytes (potassium,
      calcium, manganese, iron, and zinc), and discuss dose-appropriate guidelines for
      X-ray fluorescence microscopy of microscale biological samples.

PMID- 29045127
TI  - Revealing Dynamics of Accumulation of Systemically Injected Liposomes in the Skin
      by Intravital Microscopy.
AB  - Accumulation of intravenously injected cytotoxic liposomes in the skin induces
      serious toxicity. We used single time point and longitudinal intravital
      microscopy to understand skin accumulation dynamics of non-PEGylated and
      PEGylated liposomes after systemic injection into mice. Non-PEGylated egg
      phosphatidylcholine (PC) liposomes showed short circulation half-life (1.3 h) and
      immediate aggregation in the blood, with some aggregates lodging in skin
      microvasculature soon after the injection. At 24 h, and more prominently at 48 h
      postinjection, liposomes appeared in dermal and subdermal cells. PEGylated egg PC
      liposomes showed long circulation half-life (22 h) and no aggregation in the
      blood. PEGylated liposomes started to accumulate in the skin microvasculature as
      soon as 5 min after the injection. Within 3 h postinjection, PEGylated liposomes
      accumulated in extravascular cells in the dermis and subdermis. Liposomes were
      present in the skin for at least 7 days postinjection. A regulatory approved
      PEGylated liposomal doxorubicin (LipoDox) and empty liposomes of the same
      composition as LipoDox showed similar skin distribution as PEGylated egg PC
      liposomes, suggesting that this phenomenon is relevant to liposomes of different
      lipid composition. Decorating liposomes with shorter PEGs (350 or 700) in
      addition to PEG 2000 did not decrease the deposition. Outside the capillaries,
      liposomes partially colocalized with CD45-, F4/80+ cells. The accumulation of
      liposomes was not due to prior neutrophil/platelet binding and transport across
      endothelium. Moreover, our studies have excluded a role of complement in the skin
      accumulation of liposomes. Further understanding of mechanisms of this important
      phenomenon can improve the safety of liposomal nanocarriers.

PMID- 29045129
TI  - Cobalt-Catalyzed Asymmetric Sequential Hydroboration/Hydrogenation of Internal
      Alkynes.
AB  - A highly regio- and enantioselective cobalt-catalyzed hydroboration/hydrogenation
      of internal alkynes with HBpin and a hydrogen balloon in one pot was developed. A
      new type of chiral imidazoline iminopyridine (IIP) ligand was introduced for the
      first time in this novel and efficient strategy. This protocol used relatively
      simple and available starting materials with good functional group tolerance to
      construct more valuable chiral secondary organoboronates. The primary mechanistic
      studies illustrated that the cobalt-catalyzed regioselective hydroboration of
      alkynes did initially occur followed by HBpin-promoted and cobalt-catalyzed
      enantioselective hydrogenation of alkenylboronates.

PMID- 29045130
TI  - Correction to Selective Targeting by a Mechanism-Based Inactivator against
      Pyridoxal 5'-Phosphate-Dependent Enzymes: Mechanisms of Inactivation and
      Alternative Turnover.

PMID- 29045131
TI  - Dapsone and Nitroso Dapsone Activation of Naive T-Cells from Healthy Donors.
AB  - Dapsone (DDS) causes hypersensitivity reactions in 0.5-3.6% of patients. Although
      clinical diagnosis is indicative of a hypersensitivity reaction, studies have not
      been performed to define whether dapsone or a metabolite activates specific T
      cells. Thus, the aims of this study were to explore the immunogenicity DDS and
      nitroso DDS (DDS-NO) using peripheral blood mononuclear cells from healthy donors
      and splenocytes from mice and generate human T-cell clones to characterize
      mechanisms of T-cell activation. DDS-NO was synthesized from DDS-hydroxylamine
      and shown to bind to the thiol group of glutathione and human and mouse albumin
      through sulfonamide and N-hydroxyl sulphonamide adducts. Naive T-cell priming to
      DDS and DDS-NO was successful in three human donors. DDS-specific CD4+ T-cell
      clones were stimulated to proliferate in response to drug via a MHC class II
      restricted direct binding interaction. Cross reactivity with DDS-NO, DDS
      analogues, and sulfonamides was not observed. DDS-NO clones were CD4+ and CD8+,
      MHC class II and I restricted, respectively, and activated via a pathway
      dependent on covalent binding and antigen processing. DDS and DDS-NO-specific
      clones secreted a mixture of Th1 and Th2 cytokines, but not granzyme-B.
      Splenocytes from mice immunized with DDS-NO were stimulated to proliferate in
      vitro with the nitroso metabolite, but not DDS. In contrast, immunization with
      DDS did not activate T-cells. These data show that DDS- and DDS-NO-specific T
      cell responses are readily detectable.

PMID- 29045132
TI  - Solid-State Photoinduced Luminescence Switch for Advanced Anticounterfeiting and
      Super-Resolution Imaging Applications.
AB  - Solid-state organic photoswitches with reversible luminescence modulation
      property are highly attractive because of their wide prospects in advanced
      photonic applications, such as optical data storage, anticounterfeiting and
      bioimaging. Yet, developing such materials has long been a significant challenge.
      In this work, we construct an efficient solid-state photoswitch based on a
      spiropyran-functionalized distyrylanthracene derivative (DSA-2SP) that exhibits
      exceptional reversible absorption/luminescence modulation ability. Efficient
      photoswitching between DSA-2SP and its photoisomer DSA-2MC are facilitated by
      large free volumes induced by nonplanar molecular structures of DSA moieties, as
      well as the intramolecular hydrogen bonds between the DSA and MC moieties.
      Consequently, the excellent solid-state photochromic property of DSA-2SP is
      highly applicable as both anticounterfeiting inks and super-resolution imaging
      agents.

PMID- 29045133
TI  - The Product of Yersinia pseudotuberculosis mcc Operon Is a Peptide-Cytidine
      Antibiotic Activated Inside Producing Cells by the TldD/E Protease.
AB  - Microcin C is a heptapeptide-adenylate antibiotic produced by some strains of
      Escherichia coli. Its peptide part is responsible for facilitated transport
      inside sensitive cells where it is proteolyzed with release of a toxic warhead-a
      nonhydrolyzable aspartamidyl-adenylate, which inhibits aspartyl-tRNA synthetase.
      Recently, a microcin C homologue from Bacillus amyloliquefaciens containing a
      longer peptide part modified with carboxymethyl-cytosine instead of adenosine was
      described, but no biological activity of this compound was revealed. Here, we
      characterize modified peptide-cytidylate from Yersinia pseudotuberculosis. As
      reported for B. amyloliquefaciens homologue, the initially synthesized compound
      contains a long peptide that is biologically inactive. This compound is subjected
      to endoproteolytic processing inside producing cells by the evolutionary
      conserved TldD/E protease. As a result, an 11-amino acid long peptide with C
      terminal modified cytosine residue is produced. This compound is exported outside
      the producing cell and is bioactive, inhibiting sensitive cells in the same way
      as E. coli microcin C. Proteolytic processing inside producing cells is a novel
      strategy of peptide-nucleotide antibiotics biosynthesis that may help control
      production levels and avoid toxicity to the producer.

PMID- 29045134
TI  - Effects of the pH on the Formation and Doping Mechanisms of ZnO Nanowires Using
      Aluminum Nitrate and Ammonia.
AB  - The elucidation of the fundamental processes in aqueous solution during the
      chemical bath deposition of ZnO nanowires (NWs) using zinc nitrate and
      hexamethylenetetramine is of great significance: however, their extrinsic doping
      by foreign elements for monitoring their optical and electrical properties is
      still challenging. By combining thermodynamic simulations yielding theoretical
      solubility plots and speciation diagrams with in situ pH measurements and
      structural, chemical, and optical analyses, we report an in-depth understanding
      of the pH effects on the formation and aluminum doping mechanisms of ZnO NWs. By
      the addition of aluminum nitrate with a given relative concentration for the
      doping and of ammonia over a broad range of concentrations, the pH is shown to
      strongly influence the shape, diameter, length, and doping magnitude of ZnO NWs.
      Tuning the dimensions of ZnO NWs by inhibition of their radial growth only
      proceeds over a specific pH range, where negatively charged Al(OH)4- complexes
      are predominantly formed and act as capping agents by electrostatically
      interacting with the positively charged m-plane sidewalls. These complexes
      further favor the aluminum incorporation and doping of ZnO NWs, which only
      operate over the same pH range following thermal annealing above 200  degrees C.
      These findings reporting a full chemical synthesis diagram reveal the
      significance of carefully selecting and following the pH to control the
      morphology of ZnO NWs as well as to achieve their thermally activated extrinsic
      doping, as required for many nanoscale engineering devices.

PMID- 29045136
TI  - Centrosymmetric (Hdima)2[Ge5B3O15(OH)] and Noncentrosymmetric Na4Ga3B4O12(OH):
      Solvothermal/Surfactant-Thermal Synthesis of Open-Framework Borogermanate and
      Galloborate.
AB  - Under solvothermal/surfactant-thermal conditions, two new open-framework
      borogermanate and galloborate, centrosymmetric (Hdima)2[Ge5B3O15(OH)] (1; dima =
      dimethylamine) and noncentrosymmetric Na4Ga3B4O12(OH) (2), were obtained and
      characterized. Compound 1 contains an unusual basket-shaped Ge5B3O18(OH) cluster
      and displays a 3D open-framework layered structure. Compound 2 shows an
      interrupted 3,4-connected network constructed by alternately linked BO3 units and
      Ga3+ ions and displays weak second-harmonic-generation response.

PMID- 29045135
TI  - Structural Basis of Inhibition of ERalpha-Coactivator Interaction by High
      Affinity N-Terminus Isoaspartic Acid Tethered Helical Peptides.
AB  - Direct inhibition of the protein-protein interaction of ERalpha and its
      endogenous coactivators with a cell permeable stabilized peptide may offer a
      novel, promising strategy for combating ERalpha positive breast cancers. Here, we
      report the co-crystal structure of a helical peptide stabilized by a N-terminal
      unnatural cross-linked aspartic acid (TD) in complex with the ERalpha ligand
      binding domain (LBD). We designed a series of peptides and peptide 6 that showed
      direct and high-affinity binding to ERalpha with selective antiproliferative
      activity in ERalpha positive breast cancer cells. The co-crystal structure of the
      TD-stabilized peptide 6 in complex with ERalpha LBD further demonstrates that it
      forms an alpha helical conformation and directly binds at the coactivator binding
      site of ERalpha. Further studies showed that peptide 6W could potently inhibit
      cellular ERalpha's transcriptional activity. This approach demonstrates the
      potential of TD stabilized peptides to modulate various intracellular protein
      protein interactions involved in a range of disorders.

PMID- 29045137
TI  - Efficient Geometry Minimization and Transition Structure Optimization Using
      Interpolated Potential Energy Surfaces and Iteratively Updated Hessians.
AB  - An efficient geometry optimization algorithm based on interpolated potential
      energy surfaces with iteratively updated Hessians is presented in this work. At
      each step of geometry optimization (including both minimization and transition
      structure search), an interpolated potential energy surface is properly
      constructed by using the previously calculated information (energies, gradients,
      and Hessians/updated Hessians), and Hessians of the two latest geometries are
      updated in an iterative manner. The optimized minimum or transition structure on
      the interpolated surface is used for the starting geometry of the next geometry
      optimization step. The cost of searching the minimum or transition structure on
      the interpolated surface and iteratively updating Hessians is usually negligible
      compared with most electronic structure single gradient calculations. These
      interpolated potential energy surfaces are often better representations of the
      true potential energy surface in a broader range than a local quadratic
      approximation that is usually used in most geometry optimization algorithms.
      Tests on a series of large and floppy molecules and transition structures both in
      gas phase and in solutions show that the new algorithm can significantly improve
      the optimization efficiency by using the iteratively updated Hessians and
      optimizations on interpolated surfaces.

PMID- 29045138
TI  - Importance of the C-Terminus of Aldehyde Dehydrogenase 7A1 for Oligomerization
      and Catalytic Activity.
AB  - Aldehyde dehydrogenase 7A1 (ALDH7A1) catalyzes the terminal step of lysine
      catabolism, the NAD+-dependent oxidation of alpha-aminoadipate semialdehyde to
      alpha-aminoadipate. Structures of ALDH7A1 reveal the C-terminus is a gate that
      opens and closes in response to the binding of alpha-aminoadipate. In the closed
      state, the C-terminus of one protomer stabilizes the active site of the
      neighboring protomer in the dimer-of-dimers tetramer. Specifically, Ala505 and
      Gln506 interact with the conserved aldehyde anchor loop structure in the closed
      state. The apparent involvement of these residues in catalysis is significant
      because they are replaced by Pro505 and Lys506 in a genetic deletion (c.1512delG)
      that causes pyridoxine-dependent epilepsy. Inspired by the c.1512delG defect, we
      generated variant proteins harboring either A505P, Q506K, or both mutations
      (A505P/Q506K). Additionally, a C-terminal truncation mutant lacking the last
      eight residues was prepared. The catalytic behaviors of the variants were
      examined in steady-state kinetic assays, and their quaternary structures were
      examined by analytical ultracentrifugation. The mutant enzymes exhibit a profound
      kinetic defect characterized by markedly elevated Michaelis constants for alpha
      aminoadipate semialdehyde, suggesting that the mutated residues are important for
      substrate binding. Furthermore, analyses of the in-solution oligomeric states
      revealed that the mutant enzymes are defective in tetramer formation. Overall,
      these results suggest that the C-terminus of ALDH7A1 is crucial for the
      maintenance of both the oligomeric state and the catalytic activity.

PMID- 29045139
TI  - The G126V Mutation in the Mouse Prion Protein Hinders Nucleation-Dependent Fibril
      Formation by Slowing Initial Fibril Growth and by Increasing the Critical
      Concentration.
AB  - The middle disordered hydrophobic region of the prion protein plays a critical
      role in conformational conversion of the protein, with pathogenic as well as
      protective mutations being localized to this region. In particular, it has been
      shown that the G127V mutation in this region of the human prion protein (huPrP)
      is protective against the spread of prion disease, but the mechanism of
      protection remains unknown. In this study, quantitative analyses of the kinetics
      of fibril formation by wild-type mouse prion protein (moPrP) and G126V moPrP
      (equivalent to G127V huPrP) reveal important differences: the critical
      concentration is higher, the lag phase is longer, and the initial effective rate
      constant of fibril growth is slower for the mutant variant. The study offers a
      simple biophysical explanation for why the G127V mutation in huPrP would be
      protective in humans: the ~5-fold increase in critical concentration caused by
      the mutation likely results in the critical concentration (below which fibril
      formation cannot occur) being higher that the concentration of the protein
      present in and on cells in vivo.

PMID- 29045140
TI  - The Conformational Change in Elongation Factor Tu Involves Separation of Its
      Domains.
AB  - Elongation factor Tu (EF-Tu) is a highly conserved GTPase that is responsible for
      supplying the aminoacylated tRNA to the ribosome. Upon binding to the ribosome,
      EF-Tu undergoes GTP hydrolysis, which drives a major conformational change,
      triggering the release of aminoacylated tRNA to the ribosome. Using a combination
      of molecular simulation techniques, we studied the transition between the pre-
      and post-hydrolysis structures through two distinct pathways. We show that the
      transition free energy is minimal along a non-intuitive pathway that involves
      "separation" of the GTP binding domain (domain 1) from the OB folds (domains 2
      and 3), followed by domain 1 rotation, and, eventually, locking the EF-Tu
      conformation in the post-hydrolysis state. The domain separation also leads to a
      slight extension of the linker connecting domain 1 to domain 2. Using docking
      tools and correlation-based analysis, we identified and characterized the EF-Tu
      conformations that release the tRNA. These calculations suggest that EF-Tu can
      release the tRNA before the domains separate and after domain 1 rotates by 25
      degrees . We also examined the EF-Tu conformations in the context of the
      ribosome. Given the high degrees of sequence similarity with other translational
      GTPases, we predict a similar separation mechanism is followed.

PMID- 29045142
TI  - Measuring Intracellular Secondary Structure of a Cell-Penetrating Peptide in
      Situ.
AB  - Cell-penetrating peptides (CPPs) are short peptide sequences that can translocate
      across cellular plasma membranes and are thus potential delivery vectors for
      diagnostic and therapeutic applications. Many CPPs exhibit some sort of
      structural polymorphism, where the secondary structure of the peptide is altered
      strongly by its local environment, which is believed to facilitate membrane
      translocation and uptake. However, much less is known about the fate and
      structure of CPPs within cells largely due to measurement difficulty. Here we
      employ isotopic labeling combined with hyperspectral, quantitative coherent Raman
      microscopy to localize a model CPP-penetratin-and determine its secondary
      structure in different cellular compartments. Our results show that penetratin is
      mostly alpha-helical in the cytosol and acquires a more beta-sheet and random
      coil character in the nucleus. The increased helicity in the cytosol is similar
      to that seen in previous studies with model lipid membranes, suggesting that the
      peptide is associated with membranes in, e.g., endosomes (or lysosomes) in the
      cytosol. The ability to both localize and determine the secondary structure of a
      CPP within cells is critical for clarifying the mechanism of peptide-mediated
      translocation and delivery of cargo molecules to specific cellular destinations.

PMID- 29045141
TI  - Internal Motions of Basic Side Chains of the Antennapedia Homeodomain in the Free
      and DNA-Bound States.
AB  - Basic side chains play crucial roles in protein-DNA interactions. In this study,
      using NMR spectroscopy, we investigated the dynamics of Arg and Lys side chains
      of the fruit fly Antennapedia homeodomain in the free state and in the complex
      with target DNA. We measured 15N relaxation for Arg and Lys side chains at two
      magnetic fields, from which generalized order parameters for the cationic groups
      were determined. Mobility of the R5 side chain, which makes hydrogen bonds with a
      thymine base in the DNA minor groove, was greatly dampened. Several Lys and Arg
      side chains that form intermolecular ion pairs with DNA phosphates were found to
      retain high mobility with the order parameter being <0.6 in the DNA-bound state.
      Interestingly, some of the interfacial cationic groups in the complex were more
      mobile than in the free protein. The retained or enhanced mobility of the Arg and
      Lys side chains in the complex should mitigate the overall loss of conformational
      entropy in the protein-DNA association and allow dynamic molecular recognition.

PMID- 29045143
TI  - Reconstruction of Obliterated Characters in Polycarbonate through Spectral
      Imaging.
AB  - In forensic sciences, there is an increasing demand for nondestructive and
      reliable methods to retrieve obliterated information in polymers. This study
      demonstrates a case study for the potential of Raman spectroscopy to reconstruct
      abraded serial numbers. Residual strain and local variations in the structural
      arrangement are nondestructively imaged through peak shifts and variations of the
      full width at half-maximum of specific Raman lines, respectively. We
      qualitatively validate our approach by successfully recovering an obliterated
      letter stamped with a pressure of ~170 MPa in a polycarbonate sample, with a
      subsequent quantitative statistical analysis. The detection threshold is
      estimated from the propagation depth of plastic deformations to a value of ~750
      800 MUm, substantially larger than typical obliteration depths, 200 MUm in our
      case for an initial profile depth of 120 MUm.

PMID- 29045144
TI  - Destabilization, Propagation, and Generation of Surfactant-Stabilized Foam during
      Crude Oil Displacement in Heterogeneous Model Porous Media.
AB  - Foam flooding in porous media is of increasing interest due to its numerous
      applications such as enhanced oil recovery, aquifer remediation, and hydraulic
      fracturing. However, the mechanisms of oil-foam interactions have yet to be fully
      understood at the pore level. Here, we present three characteristic zones
      identified in experiments involving the displacement of crude oil from model
      porous media via surfactant-stabilized foam, and we describe a series of pore
      level dynamics in these zones which were not observed in experiments involving
      paraffin oil. In the displacement front zone, foam coalesces upon initial contact
      with crude oil, which is known to destabilize the liquid lamellae of the foam.
      Directly upstream, a transition zone occurs where surface wettability is altered
      from oil-wet to water-wet. After this transition takes place, a strong foam bank
      zone exists where foam is generated within the porous media. We visualized each
      zone using a microfluidic platform, and we discuss the unique physicochemical
      phenomena that define each zone. In our analysis, we also provide an updated
      mechanistic understanding of the "smart rheology" of foam which builds upon
      simple "phase separation" observations in the literature.

PMID- 29045145
TI  - Davydov Splitting and Self-Organization in a Porphyrin Layer Noncovalently
      Attached to Single Wall Carbon Nanotubes.
AB  - We study the ability of porphyrin molecules to cooperate upon adsorption on the
      sp2 curved surface of carbon nanotube. We discuss the role of the phenyl
      substituents in the cooperativity of the functionalization reaction. Moreover, a
      specific spatial organization of the molecules around the nanotube is unveiled
      through polarization sensitive experiments. Furthermore, we observe an increase
      of the energy splitting of the porphyrin main transition upon the adsorption on
      the nanotube. This effect, interpreted as a Davydov splitting, is analyzed
      quantitatively using a dipole-dipole coupling model. This study demonstrates the
      ability of porphyrin molecules to create an organized self-assembled layer at the
      surface of the nanotubes where molecules are electronically coupled together.

PMID- 29045146
TI  - Ultrahigh Vacuum Synthesis of Strain-Controlled Model Pt(111)-Shell Layers:
      Surface Strain and Oxygen Reduction Reaction Activity.
AB  - In this study, we perform ultrahigh vacuum (UHV) and arc-plasma synthesis of
      strain-controlled Pt(111) model shells on Pt-Co(111) layers with various atomic
      ratios of Pt/Co and an oxygen reduction reaction (ORR) activity enhancement trend
      against the surface strain induced by lattice mismatch between the Pt shell and
      Pt-Co alloy-core interface structures was observed. The results showed that the
      Pt(111)-shell with 2.0% compressive surface strain vs intrinsic Pt(111) lattice
      gave rise to a maximum activity enhancement, ca. 13-fold higher activity than
      that of clean Pt(111). This study clearly demonstrates that the UHV-synthesized,
      strain-controlled Pt shells furnish useful surface templates for
      electrocatalysis.

PMID- 29045147
TI  - Facile Fabrication of Durable Copper-Based Superhydrophobic Surfaces via
      Electrodeposition.
AB  - Superhydrophobic surfaces have myriad industrial applications, yet their
      practical utilization has been limited by their poor mechanical durability and
      longevity. We present a low-cost, facile process to develop superhydrophobic
      copper-based coatings via an electrodeposition route, that addresses this
      limitation. Through electrodeposition, a stable, multiscale, cauliflower shaped
      fractal morphology was obtained and upon modification by stearic acid, the
      prepared coatings show extreme water repellency with contact angle of 162 +/- 2
      degrees  and roll-off angle of about 3 degrees . Systematic studies are presented
      on coatings fabricated under different processing conditions to demonstrate good
      durability, mechanical and underwater stability, corrosion resistance, and self
      cleaning effect. The study also presents an approach for rejuvenation of slippery
      superhydrophobic nature (roll-off angle <10 degrees ) on the surfaces after long
      term water immersion. The presented process can be scaled to larger, durable
      coatings with controllable wettability for diverse applications.

PMID- 29045148
TI  - Enhancement in Elastic Bending Rigidity of Polymer Loaded Reverse Microemulsions.
AB  - Elastic bending rigidity of the surfactant shell is a crucial parameter which
      determines the phase behavior and stability of microemulsion droplets. For water
      in-oil reverse microemulsions stabilized by AOT (sodium 1,4-bis(2-ethylhexoxy)
      1,4-dioxobutane-2-sulfonate) surfactant, the elastic bending rigidity is close to
      thermal energy at room temperature (kBT) and can be modified by the presence of
      hydrophilic polymers. Here, we explore the influence of two polymers polyethylene
      glycol (PEG) and polyvinylpyrrolidone (PVP), both having nearly same size (radius
      of gyration, Rg) but different dipole moment, on elastic bending rigidity of
      water-AOT-n-decane reverse microemulsions via estimating the percolation
      temperatures (TP) and droplet radii using dielectric relaxation spectroscopy
      (DRS) and small-angle neutron scattering (SANS) techniques. Notably, an increase
      in TP is observed on introducing PEG and PVP polymers and is attributed to the
      adsorption of polymer chains onto the surfactant monolayer. The stability of the
      droplet phase of microemulsion after the incorporation of PEG and PVP polymers is
      confirmed by contrast matching SANS experiments. An enhancement in elastic
      bending rigidity of AOT surfactant shell amounting to ~46% is observed upon
      incorporation of PVP into the droplet core, whereas for PEG addition, a smaller
      increase of about 17% is recorded. We conjecture that the considerable increase
      in elastic bending rigidity of the surfactant monolayer upon introducing PVP is
      because of the strong ion-dipole interaction between anionic AOT and dipoles
      present along the PVP polymer chains. Scaling exponents extracted from the
      temperature dependent electrical conductivity measurements and the frequency
      dependent scaling of conductivity at percolation indicate the dynamic nature of
      percolation for both pure and polymer loaded reverse microemulsions. The decrease
      in activation energy of percolation upon incorporating PEG and PVP polymer
      molecules also reflects the increased stability of microemulsion droplets against
      thermal fluctuations.

PMID- 29045149
TI  - Ligand-Induced Energy Shift and Localization of Kondo Resonances in Cobalt-Based
      Complexes on Cu(111).
AB  - Magnetic sandwich complexes are of particular interest for molecular spintronics.
      Using scanning tunneling microscopy, we evidence the successful deposition of
      1,3,5-tris(eta6-borabenzene-eta5-cyclopentadienylcobalt) benzene, a molecule
      composed of three connected magnetic sandwich units, on Cu(111). Scanning
      tunneling spectra reveal two distinct spatial-dependent narrow resonances close
      to the Fermi level for the trimer molecules as well as for molecular fragments
      composed of one and two magnetic units. With the help of density functional
      theory, these resonances are interpreted as two Kondo resonances originating from
      two distinct nondegenerate d-like orbitals. These Kondo resonances are found to
      have defined spatial extents dictated by the hybridization of the involved
      orbitals with that of the ligands. These results opens promising perspectives for
      investigating complex Kondo systems composed of several "Kondo" orbitals.

PMID- 29045150
TI  - Three-Dimensional Diabatic Potential Energy Surfaces for the Photodissociation of
      Thiophenol.
AB  - New reduced three-dimensional (3D) diabatic potential energy surfaces (PESs)
      involving the 1pipi, 1pipi*, and 1pisigma* states for the nonadiabatic
      photodissociation C6H5SH(S0) + hv -> C6H5SH(1pipi*/1pisigma*) -> H + C6H5S*(A/X)
      were constructed at a high computational level, namely explicitly correlated
      multireference configuration interaction (MRCI-F12) method with the cc-pVTZ-F12
      basis. The diabatization of the PESs was achieved by a simple, efficient, and
      reliable "regularized diabatization" method [Koppel, H.; Gronki, J.; Mahapatra,
      S. J. Chem. Phys. 2001, 115, 2377-2388]. The dissociation energy of the S0 state
      and the excitation energies of the excited S1 and S2 states were found to be in
      reasonably good agreement with the experimental values. The vibronic energy
      levels of the thiophenol (PhSH) and deuterated thiophenol (PhSD) for S0 and S1
      states were calculated using a three-dimensional model, and they are in
      reasonably good agreement with the available experimental results, which validate
      the high accuracy of the adiabatic PESs and the reasonability of the diabatic
      couplings.

PMID- 29045151
TI  - Dynamic Blue Light-Inducible T7 RNA Polymerases (Opto-T7RNAPs) for Precise
      Spatiotemporal Gene Expression Control.
AB  - Light has emerged as a control input for biological systems due to its precise
      spatiotemporal resolution. The limited toolset for light control in bacteria
      motivated us to develop a light-inducible transcription system that is
      independent from cellular regulation through the use of an orthogonal RNA
      polymerase. Here, we present our engineered blue light-responsive T7 RNA
      polymerases (Opto-T7RNAPs) that show properties such as low leakiness of gene
      expression in the dark state, high expression strength when induced with blue
      light, and an inducible range of more than 300-fold. Following optimization of
      the system to reduce expression variability, we created a variant that returns to
      the inactive dark state within minutes once the blue light is turned off. This
      allows for precise dynamic control of gene expression, which is a key aspect for
      most applications using optogenetic regulation. The regulators, which only
      require blue light from ordinary light-emitting diodes for induction, were
      developed and tested in the bacterium Escherichia coli, which is a crucial cell
      factory for biotechnology due to its fast and inexpensive cultivation and well
      understood physiology and genetics. Opto-T7RNAP, with minor alterations, should
      be extendable to other bacterial species as well as eukaryotes such as mammalian
      cells and yeast in which the T7 RNA polymerase and the light-inducible Vivid
      regulator have been shown to be functional. We anticipate that our approach will
      expand the applicability of using light as an inducer for gene expression
      independent from cellular regulation and allow for a more reliable dynamic
      control of synthetic and natural gene networks.

PMID- 29045152
TI  - Discovery of Potent and Orally Bioavailable Macrocyclic Peptide-Peptoid Hybrid
      CXCR7 Modulators.
AB  - The chemokine receptor CXCR7 is an attractive target for a variety of diseases.
      While several small-molecule modulators of CXCR7 have been reported, peptidic
      macrocycles may provide advantages in terms of potency, selectivity, and reduced
      off-target activity. We produced a series of peptidic macrocycles that
      incorporate an N-linked peptoid functionality where the peptoid group enabled us
      to explore side-chain diversity well beyond that of natural amino acids. At the
      same time, theoretical calculations and experimental assays were used to track
      and reduce the polarity while closely monitoring the physicochemical properties.
      This strategy led to the discovery of macrocyclic peptide-peptoid hybrids with
      high CXCR7 binding affinities (Ki < 100 nM) and measurable passive permeability
      (Papp > 5 * 10-6 cm/s). Moreover, bioactive peptide 25 (Ki = 9 nM) achieved oral
      bioavailability of 18% in rats, which was commensurate with the observed plasma
      clearance values upon intravenous administration.

PMID- 29045153
TI  - Observation of Electron Coherence and Fabry-Perot Standing Waves at a Graphene
      Edge.
AB  - Electron surface states in solids are typically confined to the outermost atomic
      layers and, due to surface disorder, have negligible impact on electronic
      transport. Here, we demonstrate a very different behavior for surface states in
      graphene. We probe the wavelike character of these states by Fabry-Perot (FP)
      interferometry and find that, in contrast to theoretical predictions, these
      states can propagate ballistically over micron-scale distances. This is achieved
      by embedding a graphene resonator formed by gate-defined p-n junctions within a
      graphene superconductor-normal-superconductor structure. By combining
      superconducting Aharanov-Bohm interferometry with Fourier methods, we visualize
      spatially resolved current flow and image FP resonances due to p-n-p cavity
      modes. The coherence of the standing-wave edge states is revealed by observing a
      new family of FP resonances, which coexist with the bulk resonances. The edge
      resonances have periodicity distinct from that of the bulk states manifest in a
      repeated spatial redistribution of current on and off the FP resonances. This
      behavior is accompanied by a modulation of the multiple Andreev reflection
      amplitude on-and-off resonance, indicating that electrons propagate ballistically
      in a fully coherent fashion. These results, which were not anticipated by theory,
      provide a practical route to developing electron analog of optical FP resonators
      at the graphene edge.

PMID- 29045154
TI  - Enantioselective 1,3-Dipolar Cycloaddition of Methyleneindolinones with alpha
      Diazomethylphosphonate to Access Chiral Spiro-phosphonylpyrazoline-oxindoles
      Catalyzed by Tertiary Amine Thiourea and 1,5-Diazabicyclo[4.3.0]non-5-ene.
AB  - A methodology to access chiral 3,3'-spiro-phosphonylpyrazoline oxindoles via an
      asymmetric 1,3-dipolar cycloaddition reaction of substituted methyleneindolinones
      with alpha-diazomethylphosphonate in the catalysis of tertiary amine thiourea and
      1,5-diazabicyclo[4.3.0]non-5-ene (DBN) has been established. This method exhibits
      high functional group compatibility, where a wide range of methyleneindolinones
      with various substituents and heterocyclic rings are accommodated by this
      reaction. The resulting chiral 3,3'-spiro-phosphonylpyrazoline oxindoles can be
      further transformed into spiro-phosphonylcyclopropane oxindoles by ring
      contraction.

PMID- 29045155
TI  - Diamine-Appended Mg2(dobpdc) Nanorods as Phase-Change Fillers in Mixed-Matrix
      Membranes for Efficient CO2/N2 Separations.
AB  - Despite the availability of chemistries to tailor the pore architectures of
      microporous polymer membranes for chemical separations, trade-offs in
      permeability and selectivity with functional group manipulations nevertheless
      persist, which ultimately places an upper bound on membrane performance. Here we
      introduce a new design strategy to uncouple these attributes of the membrane. Key
      to our success is the incorporation of phase-change metal-organic frameworks
      (MOFs) into the polymer matrix, which can be used to increase the solubility of a
      specific gas in the membrane, and thereby its permeability. We further show that
      it is necessary to scale the size of the phase-change MOF to nanoscopic
      dimensions, in order to take advantage of this effect in a gas separation. Our
      observation of an increase in solubility and permeability of only one of the
      gases during steady-state permeability measurements suggests fast exchange
      between free and chemisorbed gas molecules within the MOF pores. While the
      kinetics of this exchange in phase-change MOFs are not yet fully understood,
      their role in enhancing the efficacy and efficiency of the separation is clearly
      a compelling new direction for membrane technology.

PMID- 29045156
TI  - Probing the Interaction Mechanism between Air Bubbles and Bitumen Surfaces in
      Aqueous Media Using Bubble Probe Atomic Force Microscopy.
AB  - Surface interactions involving deformable air bubbles have attracted tremendous
      interest in a wide range of engineering applications, such as mineral flotation
      and bitumen extraction. In this work, for the first time, the interaction forces
      between air bubbles and bitumen surfaces in complex aqueous media of varying pH,
      salinity, and salts were directly measured using a bubble probe atomic force
      microscope (AFM) technique. The AFM topographic imaging reveals that bitumen
      surface tends to be rougher and form distinct domains at high NaCl concentration
      or under strongly alkaline environment. The force measurements demonstrate the
      critical role of ionic strength and solution pH in bubble-bitumen interaction and
      attachment, which could be well described by a theoretical model based on
      Reynolds lubrication theory and augmented Young-Laplace equation by including the
      effect of disjoining pressure. In 1 mM NaCl, the electrical double layer (EDL)
      repulsion inhibited bubble-bitumen attachment, and such a repulsive effect could
      be further strengthened with increasing solution pH. In 500 mM NaCl, the
      hydrophobic attraction could lead to bubble-bitumen attachment, while a high
      solution pH could weaken the hydrophobic interaction. The addition of calcium ion
      in 500 mM NaCl could enhance the hydrophobic interaction and facilitate the
      bubble-bitumen attachment, most likely attributed to the bridging effect between
      calcium ions and the functional groups (e.g., carboxyl group) of interface-active
      molecules on bitumen surfaces, thus leading to higher surface roughness and
      hydrophobic moieties/aggregates on bitumen as confirmed by AFM imaging. Our
      results provide quantitative information on the interaction mechanism between air
      bubbles and bitumen surfaces in complex aqueous solutions at the nanoscale, which
      has useful implications to many related interfacial interactions in industrial
      processes such as oil production, oil-water separation, and wastewater treatment.

PMID- 29045157
TI  - Denticity and Mobility of the Carbonate Groups in AMCO3F Fluorocarbonates: A
      Study on KMnCO3F and High Temperature KCaCO3F Polymorph.
AB  - We report on a thorough structural study on two members of layered
      fluorocarbonates KMCO3F (M = Ca, Mn). The Ca-based member demonstrates a phase
      transition at ~320  degrees C, evidenced for the first time. The crystal
      structure of the high temperature phase (HT-KCaCO3F) was solved using neutron
      powder diffraction. A new Mn-based phase KMnCO3F was synthesized, and its crystal
      structure was solved from electron diffraction tomography data and refined from a
      combination of X-ray synchrotron and neutron powder diffraction. In contrast to
      other members of the fluorocarbonate family, the carbonate groups in the KMnCO3F
      and HT-KCaCO3F structures are not fixed to two distinct orientations
      corresponding to mono- and bidentate coordinations of the M cation. In KMnCO3F,
      the carbonate group can be considered as nearly "monodentate", forming one short
      (2.14 A) and one long (3.01 A) Mn-O contact. This topology provides more
      flexibility to the MCO3 layer and enables diminishing the mismatch between the
      MCO3 and KF layers. This conclusion is corroborated by the HT-KCaCO3F structure,
      in which the carbonate groups can additionally be tilted away from the layer
      plane thus relieving the strain arising from geometrical mismatch between the
      layers. The correlation between denticity of the carbonate groups, their
      mobility, and cation size variance is discussed. KMnCO3 orders
      antiferromagnetically below TN = 40 K.

PMID- 29045158
TI  - Rhodium-Catalyzed [4 + 3] Annulations of Sulfoximines with alpha,beta-Unsaturated
      Ketones Leading to 1,2-Benzothiazepine 1-Oxides.
AB  - A Cp*Rh(III) complex has been used as catalyst for the preparation of
      unprecedented 1,2-benzothiazepine 1-oxides by [4 + 3] cyclization of NH
      sulfoximines with alpha,beta-unsaturated ketones. For a wide range of substrates
      with various functional groups, moderate to good product yields were obtained.

PMID- 29045159
TI  - Cracking the Vaccine Code in Tuberculosis.

PMID- 29045160
TI  - Taxi driver speeding: Who, when, where and how? A comparative study between
      Shanghai and New York City.
AB  - OBJECTIVE: The 3 objectives of this study are to (1) identify the driving style
      characteristics of taxi drivers in Shanghai and New York City (NYC) using taxi
      Global Positioning System (GPS) data and make a comparative analysis; (2) explore
      the influence of different driving style characteristics on the frequency of
      speeding (who and how?) and (3) explore the influence of driving style
      characteristics, road attributes, and environmental factors on the speeding rate
      (when, where, and how?) Methods: This study proposes a driver-road-environment
      identification (DREI) method to investigate the determinant factors of taxi
      speeding violations. Driving style characteristics, together with road and
      environment variables, were obtained based on the GPS data and auxiliary
      spatiotemporal data in Shanghai and NYC. RESULTS: The daily working hours of taxi
      drivers in Shanghai (18.6 h) was far more than in NYC (8.5 h). The average
      occupancy speed of taxi drivers in Shanghai (21.3 km/h) was similar to that of
      NYC (20.3 km/h). Speeders in both cities had shorter working hours and longer
      daily driving distance than other taxi drivers, though their daily income was
      similar. Speeding drivers routinely took long-distance trips (>10 km) and
      preferred relatively faster routes. Length of segments (1.0-1.5 km) and good
      traffic condition were associated with high speeding rates, whereas central
      business district area and secondary road were associated with low speeding
      rates. Moreover, many speeding violations were identified between 4:00 a.m. and
      7:00 a.m. in both Shanghai and NYC and the worst period was between 5:00 a.m. and
      6:00 a.m. in both cities. CONCLUSIONS: Characteristics of drivers, road
      attributes, and environment variables should be considered together when studying
      driver speeding behavior. Findings of this study may assist in stipulating
      relevant laws and regulations such as stricter offense monitoring in the early
      morning, long segment supervision, shift rule regulation, and working hour
      restriction to mitigate the risk of potential crashes.

PMID- 29045161
TI  - Neurocognitive Functioning in the AALL0232 Protocol.

PMID- 29045162
TI  - Reply to I.J. Cohen.

PMID- 29045163
TI  - Real-world effectiveness of brentuximab vedotin versus physicians' choice
      chemotherapy in patients with relapsed/refractory Hodgkin lymphoma following
      autologous stem cell transplantation in the United Kingdom and Germany.
AB  - This retrospective study compared effectiveness of (brentuximab vedotin) BV to
      other chemotherapies in patients with rrHL following an autologous stem cell
      transplant (ASCT). Data originated from a medical chart review of patients
      treated in real-world clinical settings at 50 sites in the United Kingdom and
      Germany. Inverse probability of treatment weights based on propensity scores were
      used to adjust for differences in baseline characteristics between treatment
      groups. Among 312 rrHL patients included, 196 received BV and 116 received
      physicians' choice chemotherapy. Median PFS was significantly longer (27.0 months
      vs. 13.4 months; p = .0144) and 12-month OS survival greater (78.1% vs. 65.9%; p
      = .0129) with BV compared to chemotherapy. Documented adverse events included
      leukopenia (12.8%) and peripheral neuropathy (8.7%) for BV and leukopenia
      (12.1%), anemia (5.2%) and diarrhea (5.2%) for chemotherapy. In this real-world
      study, rrHL patients treated for relapse after ASCT with BV had longer median PFS
      and 12-month OS than patients receiving chemotherapy.

PMID- 29045164
TI  - eHealth literacy research-Quo vadis?
AB  - The concept of electronic health (eHealth) literacy evolved from the social and
      information sciences and describes competencies necessary to use electronic
      health services. As it is a rather new topic, and as there is no current overview
      of the state of the art in research, it is not possible to identify research
      gaps. Therefore, the objective of this viewpoint article is to increase knowledge
      on the current state of the art of research in eHealth literacy and to identify
      gaps in scientific research which should be focused on by the research community
      in the future. The article provides a current viewpoint of the concept of eHealth
      literacy and related research. Gaps can be found in terms of a missing "gold
      standard" regarding both the definition and the measurement of eHealth literacy.
      Furthermore, there is a need for identifying the implications on eHealth
      developers, which evolve from the measurement of eHealth literacy in eHealth
      users. Finally, a stronger inclusion of health professionals, both in the
      evolving concept and in the measurement of eHealth literacy, is needed in the
      future.

PMID- 29045165
TI  - Asparaginase activity levels and monitoring in patients with acute lymphoblastic
      leukemia.
AB  - Asparaginase is an integral component of multiagent chemotherapy regimens for the
      treatment of acute lymphoblastic leukemia (ALL). Adequate asparagine depletion is
      believed to be an important factor in achieving optimal therapeutic outcomes.
      Measurement of asparaginase activity allows practitioners to evaluate the
      potential effectiveness of therapy in real time. Asparaginase activity levels can
      be used to identify patients with silent inactivation and modify therapy in these
      patients. Patients with silent inactivation to asparaginase who are switched to
      therapy with an immunologically distinct asparaginase exhibit outcomes similar to
      patients who never developed silent inactivation. Despite these benefits, there
      exists no universally agreed-upon guideline for treatment adjustments based on
      asparaginase activity levels. The goal of this manuscript is to review the
      clinical evidence linking asparaginase activity levels to outcomes in patients
      with ALL and to provide an overview of how asparaginase activity levels may be
      used to guide treatment.

PMID- 29045166
TI  - Driver injury in near- and far-side impacts: Update on the effect of front
      passenger belt use.
AB  - PURPOSE: This is a study that updates earlier research on the influence of a
      front passenger on the risk for severe driver injury in near-side and far-side
      impacts. It includes the effects of belt use by the driver and passenger,
      identifies body regions involved in driver injury, and identifies the sources for
      severe driver head injury. METHODS: 1997-2015 NASS-CDS data were used to
      investigate the risk for Maximum Abbreviated Injury Scale (MAIS) 4 + F driver
      injury in near-side and far-side impacts by front passenger belt use and as a
      sole occupant in the driver seat. Side impacts were identified with GAD1 = L or R
      without rollover (rollover <= 0). Front-outboard occupants were included without
      ejection (ejection = 0). Injury severity was defined by MAIS and fatality (F) by
      TREATMNT = 1 or INJSEV = 4. Weighted data were determined. The risk for MAIS 4 +
      F was determined using the number of occupants with known injury status MAIS 0 +
      F. Standard errors were determined. RESULTS: Overall, belted drivers had greater
      risks for severe injury in near-side than far-side impacts. As a sole driver, the
      risk was 0.969 +/- 0.212% for near-side and 0.313 +/- 0.069% for far-side impacts
      (P < .005). The driver's risk was 0.933 +/- 0.430% with an unbelted passenger and
      0.596 +/- 0.144% with a belted passenger in near-side impacts. The risk was 2.17
      times greater with an unbelted passenger (NS). The driver's risk was 0.782 +/-
      0.431% with an unbelted passenger and 0.361% +/- 0.114% with a belted passenger
      in far-side impacts. The risk was 1.57 times greater with an unbelted passenger
      (P < .10). Seat belt use was 66 to 95% effective in preventing MAIS 4 + F injury
      in the driver. For belted drivers, the head and thorax were the leading body
      regions for Abbreviated Injury Scale (AIS) 4+ injury. For near-side impacts, the
      leading sources for AIS 4+ head injury were the left B-pillar, roof, and other
      vehicle. For far-side impacts, the leading sources were the other occupant, right
      interior, and roof (8.5%). CONCLUSIONS: Seat belt use by a passenger lowered the
      risk of severe driver injury in side impacts. The reduction was 54% in near-side
      impacts and 36% in far-side impacts. Belted drivers experienced mostly head and
      thoracic AIS 4+ injuries. Head injuries in the belted drivers were from contact
      with the side interior and the other occupant, even with a belted passenger.

PMID- 29045167
TI  - Identification of a Novel De Novo Heterozygous Deletion in the SOX10 Gene in
      Waardenburg Syndrome Type II Using Next-Generation Sequencing.
AB  - OBJECTIVES: Waardenburg syndrome (WS) is a rare autosomal dominant disorder
      associated with pigmentation abnormalities and sensorineural hearing loss. In
      this study, we investigated the genetic cause of WSII in a patient and evaluated
      the reliability of the targeted next-generation exome sequencing method for the
      genetic diagnosis of WS. METHODS: Clinical evaluations were conducted on the
      patient and targeted next-generation sequencing (NGS) was used to identify the
      candidate genes responsible for WSII. Multiplex ligation-dependent probe
      amplification (MLPA) and real-time quantitative polymerase chain reaction (qPCR)
      were performed to confirm the targeted NGS results. RESULTS: Targeted NGS
      detected the entire deletion of the coding sequence (CDS) of the SOX10 gene in
      the WSII patient. MLPA results indicated that all exons of the SOX10 heterozygous
      deletion were detected; no aberrant copy number in the PAX3 and microphthalmia
      associated transcription factor (MITF) genes was found. Real-time qPCR results
      identified the mutation as a de novo heterozygous deletion. CONCLUSIONS: This is
      the first report of using a targeted NGS method for WS candidate gene sequencing;
      its accuracy was verified by using the MLPA and qPCR methods. Our research
      provides a valuable method for the genetic diagnosis of WS.

PMID- 29045168
TI  - Possible causes of experiencing problems with sick leave questions in telephone
      nursing.
AB  - BACKGROUND: Registered nurses at primary health care centres in Sweden receive
      about 20 million telephone calls annually. Questions related to sick leave occur
      regularly. Previous studies conclude that those calls often are perceived as
      problematic. The aim of this study was to explore factors associated with
      problems regarding sick leave questions in telephone nursing. METHODS: A
      questionnaire was distributed to all registered nurses (n = 185) working with
      telephone nursing in 26 Swedish primary health care centres, of whom 114 (61.6%)
      responded. Based on the results of a Spearman correlation analysis a logistic
      regression analysis was performed of significant exposure variables on outcome
      (perceived problems). RESULTS: Significant exposure variables were: experience of
      telephone nursing, age, being educated in social insurance medicine, and
      frequency of telephone calls with sick leave questions. Young age was associated
      with more problems than old age. Those having education in social insurance
      medicine reported fewer problems than those who had not, and so did those having
      few telephone calls with sick leave questions as compared with those who had
      many. CONCLUSIONS: Young age, lack of education in insurance medicine, and high
      frequency of sick leave questions increased the perceived problem level in
      telephone nursing.

PMID- 29045169
TI  - Use of Topical Cannabinomimetic Palmitoylethanolamide in Ocular Surface Disease
      Associated with Antiglaucoma Medications.
AB  - PURPOSE: Chronic use of topical hypotensive therapies in glaucoma patients leads
      to chronic inflammation of the ocular surface, which decreases the success rate
      of long-term glaucoma management. The aim of this study is to evaluate the effect
      of topical palmitoylethanolamide (PEA) (Defluxa(c)), a well-known anti
      inflammatory and analgesic agent, in suppressing the ocular surface inflammation
      associated with the use of hypotensive eye drops. METHODS: In a pilot clinical
      trial, we enrolled 15 glaucomatous patients who received topical PEA (Defluxa) in
      addition to the current antiglaucoma drugs, while 15 glaucomatous patients did
      not receive any additional treatment. At 3 different time points (day 0, 15, and
      30), signs of ocular surface involvement, adverse events, visual acuity, and
      intraocular pressure were assessed. RESULTS: Topical PEA (Defluxa) was effective
      in increasing the Schirmer test (P < 0.05) and the tear film breakup time (T-BUT)
      (P < 0.0001), and improving the conjunctival hyperemia (P < 0.0001) by day 30,
      compared to baseline. Compared to control, by day 15, the conjunctival hyperemia
      score was significantly decreased in the PEA (Defluxa) group (P < 0.01), while
      the T-BUT and the Schirmer Test achieved a significant improvement by day 30 (P <
      0.05; P < 0.01). DISCUSSION: Our data suggests that topical PEA (Defluxa) is a
      safe, effective, and generally well-tolerated treatment to prevent or suppress
      ocular surface inflammation attributable to chronic glaucoma treatment.

PMID- 29045171
TI  - Type 1 Diabetes in the Hospital: What Do We Know About Glucose Control?

PMID- 29045172
TI  - Real-World Challenges of Controller Adaptation with the Artificial Pancreas.

PMID- 29045170
TI  - High Glucose Variability in Hospitalized Patients with Type 1 Diabetes Mellitus.
AB  - BACKGROUND: Glucose variability (GV) has been increasingly (or more extensively)
      studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited
      data exist on GV in hospitalized patients with T1D. MATERIALS AND METHODS:
      Retrospective single center cohort study, we analyzed in-hospital glucose
      measurements to assess GV in 736 hospitalized patients in different units over a
      consecutive 5-year period of time. GV was assessed by mean blood glucose (BG),
      Average daily risk range (ADRR), high BG index, and low BG index. To place our
      findings in context, we conducted a systematic review using Cochrane
      collaboration methodology to critically analyze current published literature on
      GV in hospitalized T1D patients. RESULTS: Overall, glycemic control was
      suboptimal with mean BG 183 +/- 51.5 mg/dL and mean ADRR 35 with only 16%
      patients being categorized as low risk (ADRR <20) for hypo or hyperglycemia.
      Patients admitted in medical units had mean BG of 194.4 +/- 42.8 mg/dL (95% CI =
      101.2-346.6) and ADRR of 39.4 +/- 16 (95% CI = 1.3-118.7), which were higher than
      the patients admitted in the surgical units (mean BG 168.1 +/- 35.7 (95% CI =
      74.8-301.8) and mean ADRR (28.8 +/- 13.1 [95% CI = 0.3-93.1]). For the systematic
      review, initial search yielded 2336 studies for screening, however, none of them
      had data specific for T1D. CONCLUSION: GV is high in hospitalized T1D patients
      admitted at our tertiary care center. Review of the literature shows paucity of
      data regarding GV in hospitalized patients with T1D.

PMID- 29045173
TI  - The International Rare Diseases Research Consortium Announces New Vision and
      Goals.

PMID- 29045174
TI  - Novel Genetic Markers for Common Degenerative Orthopedic Diseases.

PMID- 29045177
TI  - Outcomes of Endovascular Management of Late Vascular Hemorrhage After Pancreatic
      Transplant.
AB  - OBJECTIVE: The aim of this retrospective study is to evaluate the endovascular
      treatment of hemorrhage in the nonperioperative setting in pancreas transplant
      recipients. MATERIALS AND METHODS: All angiograms performed between January 1,
      1999, and June 1, 2016, to treat hemorrhage after pancreatic transplant at a
      single large-volume transplant center were reviewed. Fourteen patients who
      underwent 21 angiograms were identified. The patients' charts were reviewed for
      clinical indications, technical aspects of the endovascular interventions,
      outcomes, and complications. RESULTS: The mean number of angiograms was 1.5 per
      patient. The primary and primary assisted clinical success rates were 64.3% (9/14
      patients) and 71.4% (10/14 patients), respectively. Five patients (35.7%)
      experienced complications. At presentation, eight patients had functioning grafts
      and seven of these eight patients (87.5%) maintained graft function. CONCLUSION:
      It is critical to recognize transplant-related hemorrhage after pancreas
      transplant. Endovascular management is associated with high clinical success and
      rarely results in loss of graft function, suggesting that it should be a
      consideration for first-line therapy in this patient population.

PMID- 29045176
TI  - Computer-Aided Diagnosis of Ground-Glass Opacity Nodules Using Open-Source
      Software for Quantifying Tumor Heterogeneity.
AB  - OBJECTIVE: The purposes of this study are to develop quantitative imaging
      biomarkers obtained from high-resolution CTs for classifying ground-glass nodules
      (GGNs) into atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS),
      minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC); to
      evaluate the utility of contrast enhancement for differential diagnosis; and to
      develop and validate a support vector machine (SVM) to predict the GGN type.
      MATERIALS AND METHODS: The heterogeneity of 248 GGNs was quantified using custom
      software. Statistical analysis with a univariate Kruskal-Wallis test was
      performed to evaluate metrics for significant differences among the four GGN
      groups. The heterogeneity metrics were used to train a SVM to learn and predict
      the lesion type. RESULTS: Fifty of 57 and 51 of 57 heterogeneity metrics showed
      statistically significant differences among the four GGN groups on unenhanced and
      contrast-enhanced CT scans, respectively. The SVM predicted lesion type with
      greater accuracy than did three expert radiologists. The accuracy of classifying
      the GGNs into the four groups on the basis of the SVM algorithm was 70.9%,
      whereas the accuracy of the radiologists was 39.6%. The accuracy of SVM in
      classifying the AIS and MIA nodules was 73.1%, and the accuracy of the
      radiologists was 35.7%. For indolent versus invasive lesions, the accuracy of the
      SVM was 88.1%, and the accuracy of the radiologists was 60.8%. We found that
      contrast enhancement does not significantly improve the differential diagnosis of
      GGNs. CONCLUSION: Compared with the GGN classification done by the three
      radiologists, the SVM trained regarding all the heterogeneity metrics showed
      significantly higher accuracy in classifying the lesions into the four groups,
      differentiating between AIS and MIA and between indolent and invasive lesions.
      Contrast enhancement did not improve the differential diagnosis of GGNs.

PMID- 29045178
TI  - Harmonizing Breast Cancer Screening Recommendations: Metrics and Accountability.
AB  - OBJECTIVE: The purposes of this article are to summarize breast cancer screening
      recommendations and discuss their differences and similarities and to explain the
      differences between two national databases to aid in interpretation of their
      benchmarks. CONCLUSION: The American College of Radiology, American Cancer
      Society, and U.S. Preventive Services Task Force all agree that annual
      mammography beginning at age 40 saves the most lives, and all acknowledge a
      woman's right to choose when to begin and stop screening. The National
      Mammography Database (NMD) differs from the Breast Cancer Surveillance Consortium
      database in that it acquires data using the same approach used by almost all
      mammography facilities in the United States. Therefore, NMD benchmarks, which
      include standard metrics, provide more meaningful comparisons to help mammography
      facilities and radiologists improve performance.

PMID- 29045179
TI  - Clinical Relevance of the Feces Sign in Small-Bowel Obstruction Due to Adhesions
      Depends on Its Location.
AB  - OBJECTIVE: The objective of our study was to evaluate if the feces sign can be
      used to predict successful nonoperative treatment or progression to ischemia in
      patients with small-bowel obstruction (SBO) due to adhesions. MATERIALS AND
      METHODS: For this single-center retrospective observational study involving a
      blinded independent review by two radiologists of 237 consecutive CT examinations
      of 216 patients with SBO due to adhesions (age: mean, 70.9 years; median, 74
      years; interquartile range, 62-84 years), the location of the transition zone
      (TZ), number of TZs, and presence and location of the feces sign relative to the
      TZ were recorded. The reference standard for diagnosing ischemia was surgical and
      pathologic findings (n = 108 CT examinations) or, when treatment was nonoperative
      (n = 129 CT examinations), clinical outcome. Factors associated with successful
      nonoperative treatment and ischemia were identified by univariate and
      multivariate analyses. RESULTS: A feces sign was seen in 88 of 237 CT
      examinations (37.1%). The feces sign was at the TZ, which we refer to as the "TZ
      feces" sign, in 82 of 88 (93.2%) patients; between two TZs, which we refer to as
      the "trapped feces" sign, in 14 (15.9%) patients; and in both locations in eight
      (9.1%) patients. By univariate analysis, an isolated TZ feces sign was associated
      positively with successful nonoperative treatment (odds ratio [OR], 3.37; 95% CI,
      1.71-6.66; p < 0.001) and negatively with ischemia (OR, 0.33; 95% CI, 0.13-0.85;
      p = 0.02). Combined TZ and trapped feces signs were associated with ischemia (OR,
      24.16; 95% CI, 2.86-203.89; p = 0.003). By multivariate analysis, regardless of
      the location of the feces sign, the feces sign was not significantly associated
      with successful nonoperative treatment or progression to ischemia. CONCLUSION:
      The feces sign is common and helps to identify the TZ. Among the CT signs of SBO,
      the feces sign does not independently help to predict successful nonoperative
      treatment or progression to ischemia.

PMID- 29045180
TI  - Quantitative Liver MRI-Biopsy Correlation in Pediatric and Young Adult Patients
      With Nonalcoholic Fatty Liver Disease: Can One Be Used to Predict the Other?
AB  - OBJECTIVE: The purpose of this study is to determine the relationships between
      quantitative liver MRI measurements and liver biopsy findings in pediatric and
      young adult patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND
      METHODS: Data were obtained from a registry that prospectively enrolls pediatric
      and young adult patients with biopsy-confirmed NAFLD at our tertiary medical
      center with parent or guardian and subject informed consent, as appropriate.
      Patients enrolled between November 2007 and June 2016 with a quantitative liver
      MRI examination within 6 months of biopsy were included (n = 69). Liver stiffness
      (kilopascals), volume (milliliters), and fat fraction (percentage) were extracted
      from MRI records. Multiple linear regression was used to determine the
      relationships between NAFLD activity score and quantitative MRI measures, and
      between MRI liver stiffness and histopathologic scores (steatosis, lobular
      inflammation, portal inflammation, hepatocyte ballooning, and fibrosis).
      Histopathologic data were extracted from medical records, with severity graded by
      hepatopathologists using Non-alcoholic Steatohepatitis (NASH) Clinical Research
      Network criteria. Ordinal logistic regression was used to assess the relationship
      between categoric NAFLD severity (simple steatosis vs NASH vs NASH with
      significant fibrosis) and MRI measures. RESULTS: The mean (+/- SD) patient age at
      the time of MRI was 14.3 +/- 2.8 years (range, 8-21 years); 25 (36.2%) patients
      were female. Liver biopsy was performed within a mean of 64.4 days of the MRI
      examination. There was a positive correlation between histopathologic steatosis
      and MRI liver fat fraction (rho = 0.57; p < 0.0001). MRI fat fraction was the
      only significant imaging predictor of NAFLD activity score (p = 0.017). Fibrosis
      score was the only significant histopathologic predictor of MRI liver stiffness
      (p = 0.001). MRI liver volume was the only imaging predictor of categoric NAFLD
      severity (odds ratio = 1.001; 95% CI, 1.000-1.002; p = 0.007). CONCLUSION: There
      was significant positive correlation between histopathologic and MRI liver fat
      measurements in our cohort. MRI liver stiffness did not predict the severity of
      fatty liver disease in children and young adults.

PMID- 29045181
TI  - Ductal Carcinoma In Situ: The Whole Truth.
AB  - OBJECTIVE: Ductal carcinoma in situ (DCIS) is a noninvasive malignant breast
      disease traditionally described as a precursor lesion to invasive breast cancer.
      With screening mammography, DCIS now accounts for approximately 20% of newly
      diagnosed cancer cases. DCIS is not well understood because of its heterogeneous
      nature. CONCLUSION: Studies have aimed to assess prognostic factors to
      characterize its risk of invasive potential; however, there still remains a lack
      of uniformity in workup and treatment. We summarize current knowledge of DCIS and
      the ongoing controversies.

PMID- 29045182
TI  - Validity of Radiograph-Based Infrapatellar Fat Pad Opacity Grading for Assessing
      Knee Synovitis: Correlation With Contrast-Enhanced MRI.
AB  - OBJECTIVE: The purpose of this study was to determine the validity of
      infrapatellar fat pad (IPFP) opacity grading based on lateral knee radiography
      for assessing knee synovitis using correlation with contrast-enhanced (CE) MRI.
      MATERIALS AND METHODS: Retrospective reviews of radiographs and CE knee MR images
      from 79 patients were independently performed by two radiologists. They evaluated
      IPFP opacity alteration (IPFPCR) and joint effusion grades on lateral knee
      conventional radiographs, IPFP signal intensity alteration (IPFPMR) and joint
      effusion grades on CE MR images, and synovitis (SYNMR) grade in nine divided
      regions, three compartments (parapatellar, periligamentous, perimeniscal), and
      the whole knee on CE MR images. Correlations between radiographic grades and MRI
      assessments were evaluated using Spearman correlation tests, and the correlation
      coefficients (rho) were compared. Interobserver agreement was evaluated using
      weighted kappa values. RESULTS: The IPFPCR grade was very highly correlated with
      the IPFPMR grade (rho = 0.906, p < 0.001) and highly correlated with SYNMR grades
      from four regions (suprapatellar, infrapatellar, intercondylar, lateral
      parapatellar recess), the parapatellar compartment, and the whole knee (rho =
      0.614-0.740, all p < 0.001). The IPFPCR grade was moderately correlated with the
      SYNMR grades of the remaining five regions and two compartments (rho = 0.457
      0.547, all p < 0.001). The differences between correlation coefficients for SYNMR
      grades and the IPFPCR and IPFPMR grades were not statistically significant (p =
      0.290-1.0). Interobserver reliabilities were excellent or good for IPFPCR,
      IPFPMR, and SYNMR grades (kappa = 0.661-1.000). CONCLUSION: IPFPCR grade
      assessment enables valid evaluation and reporting of knee synovitis, especially
      in the parapatellar compartment and the whole knee.

PMID- 29045183
TI  - Supplemental Screening With Automated Breast Ultrasound in Women With Dense
      Breasts: Comparing Notification Methods and Screening Behaviors.
AB  - OBJECTIVE: Supplemental screening with ultrasound has been shown to detect
      additional breast malignancies in women with dense breast tissue and normal
      mammogram findings. The frequency of supplemental screening with automated breast
      ultrasound and the effect and type of breast tissue density notification on
      automated screening breast ultrasound utilization rates are unknown. MATERIALS
      AND METHODS: We examined normal mammogram results letters for patients with
      heterogeneously or extremely dense breast tissue between July 1, 2013, and June
      30, 2014, by type of results letter, notification method, and sociodemographic
      characteristics. Logistic regression was used to examine the association between
      type of results letter and subsequent automated screening breast ultrasound.
      RESULTS: Among 3012 women with dense breast tissue and normal mammogram findings,
      15% returned for supplemental automated screening breast ultrasound within 18
      months of results letter notification. Compared with a similarly sized control
      group of women who did not undergo automated ultrasound, a significantly greater
      proportion of patients (86.9%) returned for breast ultrasound if they received a
      results letter indicating breast density in combination with a courtesy phone
      call (p < 0.001). Patients who received results letters with breast density
      notification including a statement that they may benefit from additional
      screening with automated breast ultrasound examination were 9.91 times (95% CI,
      6.08-16.16) more likely to return for the examination than patients who did not
      receive breast density notification or mention of supplemental screening.
      CONCLUSION: Patient breast density notification and radiologists' recommendations
      for supplemental screening with breast ultrasound increase patient utilization of
      automated screening breast ultrasound examinations.

PMID- 29045184
TI  - Predictive Factors of Retear in Patients With Repaired Rotator Cuff Tear on
      Shoulder MRI.
AB  - OBJECTIVE: This study aimed to find independent prognostic factors related to
      retear of the rotator cuff tendon in patients with repaired full-thickness
      supraspinatus tendon tear by evaluation of pre- and postoperative MR images.
      MATERIALS AND METHODS: Shoulder MR images were retrospectively analyzed for 83
      patients who had undergone arthroscopic or open rotator cuff repair with
      acromioplasty for full-thickness supraspinatus tendon tear from April 2014 to
      March 2015. On preoperative MR images, the type of rotator cuff tear, extent of
      retraction of torn tendon, anteroposterior (AP) dimension of torn tendon, signal
      intensity of tear edge, degree of fat infiltration in supraspinatus and
      infraspinatus muscles, and acromiohumeral interval (AHI) were assessed.
      Postoperative cuff integrity seen on MR images was classified into five
      categories according to the Sugaya classification system, and patients were
      categorized into retear or intact groups. Factors assessed on preoperative MR
      images were compared between the two groups. RESULTS: The overall retear rate was
      57.8%. Significant differences were observed between the retear and intact groups
      in terms of the mean values of the extent of tendon retraction (20.4 vs 11.7 mm),
      AP dimension of the tear (16.1 vs 11.4 mm), AHI (6.8 vs 8.7 mm), and degree of
      fat infiltration of the supraspinatus and infraspinatus muscles (for the
      supraspinatus muscle, 3, 30, and 15 patients in the retear group vs 5, 27, and
      three patients in the intact group had Goutallier grade 1, grade 2, and grades 3
      and 4 infiltration, respectively; for the infraspinatus muscle, 27, 12, and 9
      patients in the retear group vs 29, 5, and one patient in the intact group had
      Goutallier grade 1, grade 2, and grades 3 and 4 infiltration, respectively).
      Multivariable analysis revealed that AHI and degree of tendon retraction were
      independent predictive factors affecting retear of rotator cuff after repair.
      CONCLUSION: The retear rate of repaired rotator cuff tendon was about 57.8%.
      Independent prognostic factors of retear were degree of tendon retraction and AHI
      on preoperative MR images.

PMID- 29045185
TI  - Apparent Diffusion Coefficient Values of Prostate Cancer: Comparison of 2D and 3D
      ROIs.
AB  - OBJECTIVE: The purpose of this study was to compare the reproducibility and
      diagnostic performance of 2D and 3D ROIs for prostate apparent diffusion
      coefficient (ADC) measurements. MATERIALS AND METHODS: The study included 56
      patients with prostate cancer undergoing 3-T MRI including DWI (b = 50 and 1000
      s/mm2) before radical prostatectomy. Histologic findings from prostatectomy
      specimens were reviewed to denote each patient's dominant tumor and a benign
      region with visually decreased ADC. Three readers independently measured the ADCs
      of both areas using an ROI placed on a single slice through the lesion (2D) and
      an ROI encompassing all slices through the lesion (3D). Readers repeated
      measurements after 3 weeks. Assessment included Bland-Altman analysis
      (coefficient of repeatability [CR] in which lower values indicated higher
      reliability) and ROC analysis. RESULTS: For intrareader variability, the CRs
      across readers for all ROIs were 9.9% for 2D and 9.3% for 3D. For tumor ROIs the
      CRs were 10.6% for 2D and 9.6% for 3D. For interreader variability, the CRs
      across readers for all ROIs were 17.1% for 2D and 20.5% for 3D and for tumor ROIs
      were 17.9% for 2D and 22.2% for 3D. For combined reader data, the AUCs for benign
      and malignant findings were 0.77 for 2D and 0.78 for 3D (p = 0.146). For
      differentiating Gleason score (GS) 3 + 3 from GS > 3 + 3 tumors, the AUCs were
      0.92 for 2D and 0.92 for 3D ROIs (p = 0.649). For differentiating GS <= 3 + 4
      from GS >= 4 + 3 tumors, the AUCs were 0.70 for 2D and 0.67 for 3D ROIs (p =
      0.004). CONCLUSION: Use of a 3D ROI did not improve intrareader or interreader
      reproducibility or diagnostic performance compared with use of a 2D ROI for
      prostate ADC measurements. Interreader reproducibility of 2D ROIs was suboptimal
      nonetheless.

PMID- 29045186
TI  - Considering the Benefits and Risks of Research Participants' Access to Sequence
      Data.
AB  - The use of sequencing technologies has greatly expanded in both research and
      clinical settings. The generation of voluminous datasets has raised several
      issues regarding data sharing and access. Current regulations require clinical
      laboratories and some research laboratories to provide access to test data,
      including sequencing data, directly to patients upon request. There is some
      controversy over whether this access right may be somewhat broader, encompassing
      research data as well-a question beyond the scope of this article. It is clear
      that in the research setting, deposition of sequencing data into public or
      private databases often occurs, although little information exists about the
      return of data files to research participants (in contrast to the extensive
      deliberations regarding return of results). Thus, further consideration of the
      issue of access to data files is warranted as well as more effort to understand
      both patients' and research participants' use of the data.

PMID- 29045187
TI  - LETTER TO THE EDITOR.

PMID- 29045188
TI  - RAPID EVOLUTION OF THYROID DYSFUNCTION IN PATIENTS TREATED WITH NIVOLUMAB.
AB  - OBJECTIVE: To describe the evolution of thyroid dysfunction in a series of
      patients with cancer treated with the immune checkpoint inhibitor anti-programmed
      cell death protein-1 (PD-1) monoclonal antibody, nivolumab. METHODS: Cases of
      thyroid dysfunction after initiation of checkpoint inhibitor treatment were
      identified from the Division of Endocrinology clinical practice at Mount Sinai
      Hospital, New York from April 2016 to February 2017. Charts were reviewed to
      identify patients treated with nivolumab with new onset of thyroid dysfunction.
      RESULTS: Nine cases of thyroid function in patients who were treated with
      nivolumab were identified. There were 4 male and 5 female patients, with a mean
      age of 66 years (range 50-76 years). Seven patients ultimately developed
      hypothyroidism. Five of the 7 patients developed abnormal thyroid function tests
      within the first 90 days of starting therapy (range 21-84 days), 3 of whom had
      transient hyperthyroidism. Transient hyperthyroidism evolved rapidly to
      hypothyroidism; elevated thyroid-stimulating hormone (TSH) levels were detected
      within 16 to 32 days of the last documented low TSH. In the 2 patients without a
      hyperthyroid phase, TSH levels >50 were found 18 to 28 days after the last normal
      TSH value. CONCLUSION: As the use of immune checkpoint inhibitor therapy
      increases, the need for prompt diagnosis and treatment of drug-induced thyroid
      disease will become more important. As illustrated in this case series, in
      contrast to other causes of auto-immune thyroiditis, hypothyroidism can develop
      rapidly within 3 months of treatment. Close monitoring is necessary to detect the
      development of thyroid dysfunction and avoid preventable morbidity.
      ABBREVIATIONS: Anti-TPO Abs = anti-thyroglobulin antibodies; CT = computed
      tomography; CTLA-4 = cytotoxic T-lymphocyte-associated protein 4; FDA = U.S. Food
      & Drug Administration; FDG-PET = fluorodeoxyglucose-positron emission tomography;
      PD-1 = programmed cell death protein-1; PD-L1 = programmed death-ligand 1; T3 =
      triiodothyronine; T4 = thyroxine; TG = thyroglobulin; TPO = thyroperoxidase; TSH
      = thyroid-stimulating hormone.

PMID- 29045189
TI  - Effect of Climatic Variables on Abundance and Dispersal of Lecanosticta acicola
      Spores and Their Impact on Defoliation on Eastern White Pine.
AB  - The disease complex white pine needle damage (WPND), first reported in 2006, has
      now escalated to an epidemic state across the northeastern United States.
      Although this complex is composed of several fungal species, Lecanosticta acicola
      is considered to be the primary causal agent. Knowledge regarding the
      epidemiology, specific climatic factors that affect the spread of L. acicola on
      eastern white pine (Pinus strobus) in natural forest settings, and potential
      risks repeated defoliation may have on tree health is limited. Therefore, this
      study examined how climatic variables affect the abundance and distance of spore
      dispersal of L. acicola and compared litterfall caused by defoliation versus
      natural needle abscission. Conidia were observed on spore traps from May through
      August, with a peak in abundance occurring in June, corresponding to the
      defoliation of second- and third-year foliage measured in litter traps. During
      peak spore production, relative humidity and the occurrence of rainfall was found
      to have the greatest influence on spore abundance. Our results will aid managers
      in determining how far from infected trees natural regeneration will likely be
      affected and predicting future disease severity based on climatic conditions.

PMID- 29045190
TI  - Anaerobic Soil Disinfestation Reduces Germination and Affects Colonization of
      Sclerotium rolfsii Sclerotia.
AB  - Growth chamber and field studies were conducted with organic amendment mixtures
      of carbon (C) and nitrogen (N) at C:N ratios 10:1, 20:1, 30:1, and 40:1 and
      amendment rates of C at 2, 4, 6, and 8 mg/g of soil (C:N ratio 30:1) to evaluate
      anaerobic soil disinfestation (ASD) effects on germination and colonization of
      Sclerotium rolfsii. In the growth chamber, sclerotial germination was reduced in
      all ASD treatments regardless of C:N ratio (0.6 to 8.5% germination) or amendment
      rate (7.5 to 46%) as compared with nonamended controls (21 to 36% and 61 to 96%,
      respectively). ASD treatment increased Trichoderma spp. colonization of
      sclerotia, with consistently higher colonization in ASD treatments with amendment
      rates of C at 2 or 4 mg/g of soil (>87% colonization) compared with nonamended
      controls (<50% colonization). In the 2014 field study, sclerotial germination was
      reduced by 24 to 30% in ASD treatments when compared with the nonamended control.
      Sclerotial colonization by Trichoderma spp. was predominant; however, other
      potential mycoparasites (i.e., Aspergillus spp., Fusarium spp., zygomycetes, and
      other fungi) were present in the field study. Amendment C:N ratios in the range
      of 10:1 to 40:1 were equally effective in reducing sclerotial germination and
      enhancing colonization by potentially beneficial mycoparasites of sclerotia.

PMID- 29045191
TI  - The efficacy of resistance training in hypoxia to enhance strength and muscle
      growth: A systematic review and meta-analysis.
AB  - Recent studies have reported that resistance training in hypoxia (RTH) may
      augment muscle size and strength development. However, consensus on the effects
      of RTH via systematic review and meta-analysis is not yet available. This work
      aimed to systematically review studies which have investigated using RTH versus
      normoxic resistance training (NRT) to improve muscular size and strength, and to
      perform a meta-analysis to determine the effect of RTH on these adaptive
      parameters. Searches were conducted in PubMed, Web of Science and the Cochrane
      Library from database inception until 17 June 2017 for original articles
      assessing the effects of RTH on muscle size and strength versus NRT. The effects
      on outcomes were expressed as standardized mean differences (SMD). Nine studies
      (158 participants) reported on the effects of RTH versus NRT for muscle cross
      sectional area (CSA) (n = 4) or strength (n = 6). RTH significantly increased CSA
      (SMD = 0.70, 95% confidence intervals (CI) 0.05, 1.35; p = .04) and strength (SMD
      = 1.88; 95% CI = 1.20, 2.56; p < .00001). However, RTH did not produce
      significant change in CSA (SMD = 0.24, 95% CI -0.19, 0.68, p = .27) or strength
      (SMD = 0.20; 95% CI = -0.27, 0.78; p = .23) when compared to NRT. Although RTH
      improved muscle size and strength, this protocol did not provide significant
      benefit over resistance training in normoxia. Nevertheless, this paper identified
      marked differences in methodologies for implementing RTH, and future research
      using standardized protocols is therefore warranted.

PMID- 29045193
TI  - A Microdosimetric-Kinetic Model of Cell Killing by Irradiation from Permanently
      Incorporated Radionuclides.
AB  - An expression for the surviving fraction of a replicating population of cells
      exposed to permanently incorporated radionuclide is derived from the
      microdosimetric-kinetic model. It includes dependency on total implant dose,
      linear energy transfer (LET), decay rate of the radionuclide, the repair rate of
      potentially lethal lesions in DNA and the volume doubling time of the target
      population. This is used to obtain an expression for the biologically effective
      dose ( BEDalpha/beta) based on the minimum survival achieved by the implant that
      is equivalent to, and can be compared and combined with, the BEDalpha/beta
      calculated for a fractionated course of radiation treatment. Approximate
      relationships are presented that are useful in the calculation of BEDalpha/beta
      for alpha- or beta-emitting radionuclides with half-life significantly greater
      than, or nearly equal to, the approximately 1-h repair half-life of radiation
      induced potentially lethal lesions.

PMID- 29045194
TI  - Testing an AAC system that transforms pictograms into natural language with
      persons with cerebral palsy.
AB  - In this article, we describe a compansion system that transforms the telegraphic
      language that comes from the use of pictogram-based augmentative and alternative
      communication (AAC) into natural language. The system was tested with four
      participants with severe cerebral palsy and ranging degrees of linguistic
      competence and intellectual disabilities. Participants had used pictogram-based
      AAC at least for the past 30 years each and presented a stable linguistic
      profile. During tests, which consisted of a total of 40 sessions, participants
      were able to learn new linguistic skills, such as the use of basic verb tenses,
      while using the compansion system, which proved a source of motivation. The
      system can be adapted to the linguistic competence of each person and required no
      learning curve during tests when none of its special features, like gender,
      number, verb tense, or sentence type modifiers, were used. Furthermore,
      qualitative and quantitative results showed a mean communication rate increase of
      41.59%, compared to the same communication device without the compansion system,
      and an overall improvement in the communication experience when the output is in
      natural language. Tests were conducted in Catalan and Spanish.

PMID- 29045192
TI  - A DNA vaccine delivered by dermal electroporation fully protects cynomolgus
      macaques against Lassa fever.
AB  - Lassa virus (LASV) is an ambisense RNA virus in the Arenaviridae family and is
      the etiological agent of Lassa fever, a severe hemorrhagic disease endemic to
      West and Central Africa. 1,2 There are no US Food and Drug Administration (FDA)
      licensed vaccines available to prevent Lassa fever. 1,2 in our previous studies,
      we developed a gene-optimized DNA vaccine that encodes the glycoprotein precursor
      gene of LASV (Josiah strain) and demonstrated that 3 vaccinations accompanied by
      dermal electroporation protected guinea pigs from LASV-associated illness and
      death. Here, we describe an initial efficacy experiment in cynomolgus macaque
      nonhuman primates (NHPs) in which we followed an identical 3-dose vaccine
      schedule that was successful in guinea pigs, and a follow-on experiment in which
      we used an accelerated vaccination strategy consisting of 2 administrations,
      spaced 4 weeks apart. In both studies, all of the LASV DNA-vaccinated NHPs
      survived challenge and none of them had measureable, sustained viremia or
      displayed weight loss or other disease signs post-exposure. Three of 10 mock
      vaccinates survived exposure to LASV, but all of them became acutely ill post
      exposure and remained chronically ill to the study end point (45 d post
      exposure). Two of the 3 survivors experienced sensorineural hearing loss
      (described elsewhere). These results clearly demonstrate that the LASV DNA
      vaccine combined with dermal electroporation is a highly effective candidate for
      eventual use in humans.

PMID- 29045195
TI  - Strengthening the ACA for the Long Term.

PMID- 29045196
TI  - Lessons from the Latest ACA Battle.

PMID- 29045197
TI  - Triple Therapy for Atrial Fibrillation after PCI.

PMID- 29045198
TI  - Instantaneous Wave-free Ratio versus Fractional Flow Reserve.

PMID- 29045199
TI  - Instantaneous Wave-free Ratio versus Fractional Flow Reserve.

PMID- 29045200
TI  - Instantaneous Wave-free Ratio versus Fractional Flow Reserve.

PMID- 29045201
TI  - Instantaneous Wave-free Ratio versus Fractional Flow Reserve.

PMID- 29045202
TI  - Amyotrophic Lateral Sclerosis.

PMID- 29045203
TI  - Incidental Findings on Brain Imaging in the General Pediatric Population.

PMID- 29045204
TI  - Telehealth.

PMID- 29045205
TI  - Effect of a Hospital-wide Measure on the Readmissions Reduction Program.
AB  - BACKGROUND: The Hospital Readmissions Reduction Program penalizes hospitals that
      have high 30-day readmission rates across specific conditions. There is support
      for changing to a hospital-wide readmission measure to broaden hospital
      eligibility and provide incentives for improvement across more conditions.
      METHODS: We used Medicare claims from 2011 through 2013 to evaluate the number of
      hospitals that were eligible for penalties, in that they met a volume threshold
      of 25 admissions over a 3-year period for a specific condition or 25 admissions
      over a 1-year period for the cohorts included in the hospital-wide measure. We
      estimated the expected effects that changing from the condition-specific
      readmission measures to a hospital-wide measure would have on average penalties
      for safety-net hospitals (i.e., hospitals that treat a large proportion of low
      income patients) and other hospitals. RESULTS: Our sample included 6,807,899
      admissions for the hospital-wide measure and 4,392,658 admissions for the
      condition-specific measures. Of 3443 hospitals, 688 were considered to be safety
      net hospitals. Changing to the hospital-wide measure would result in 76 more
      hospitals being eligible to receive penalties. The hospital-wide measure would
      increase penalties (mean [+/-SE] Medicare payment reductions across all
      hospitals) from 0.42+/-0.01% to 0.89+/-0.01% of Medicare base diagnosis-related
      group payments. It would also increase the disparity in penalties between safety
      net hospitals and other hospitals from -0.03+/-0.02 to 0.41+/-0.06 percentage
      points. CONCLUSIONS: A transition to a hospital-wide readmission measure would
      only modestly increase the number of hospitals eligible for penalties and would
      substantially increase the penalties for safety-net hospitals.

PMID- 29045206
TI  - A Devastating Delay - Zika and the Implementation Gap.

PMID- 29045208
TI  - Recalibrating Privacy Protections to Promote Patient Engagement.

PMID- 29045207
TI  - Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to
      TNF Inhibitors.
AB  - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under
      investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib
      in patients with active psoriatic arthritis who had previously had an inadequate
      response to tumor necrosis factor (TNF) inhibitors. METHODS: In this 6-month
      randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned
      395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib
      administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily
      (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3
      months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice
      daily at 3 months (65 patients). Data from the patients who received placebo
      during the first 3 months of the trial were pooled. The primary end points were
      the percentage of patients who had at least 20% improvement according to the
      criteria of the American College of Rheumatology (ACR20 response) and the change
      from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ
      DI; scores range from 0 to 3, with higher scores indicating greater disability)
      at the month 3 analysis. RESULTS: At 3 months, the rates of ACR20 response were
      50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared
      with 24% with placebo (P<0.001 for both comparisons); the corresponding mean
      changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with 
      0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the
      patients who received the 5-mg dose of tofacitinib continuously and in 6% who
      received the 10-mg dose continuously. Over the course of 6 months, there were
      four serious infections, three herpes zoster infections, one myocardial
      infarction, and one ischemic stroke among the patients who received tofacitinib
      continuously. Elevations of aspartate and alanine aminotransferase concentrations
      of three or more times the upper limit of the normal range occurred in more
      patients who received tofacitinib continuously than in patients who received
      placebo followed by tofacitinib. CONCLUSIONS: In this trial involving patients
      with active psoriatic arthritis who had had an inadequate response to TNF
      inhibitors, tofacitinib was more effective than placebo over 3 months in reducing
      disease activity. Adverse events were more frequent with tofacitinib than with
      placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439
      .).

PMID- 29045209
TI  - Takotsubo Cardiomyopathy.

PMID- 29045210
TI  - Decompression Sickness.

PMID- 29045211
TI  - Case 32-2017. A 64-Year-Old Man with Dyspnea, Wheezing, Headache, Cough, and
      Night Sweats.

PMID- 29045212
TI  - Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.
AB  - BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is under
      investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib
      in patients with active psoriatic arthritis who previously had an inadequate
      response to conventional synthetic disease-modifying antirheumatic drugs
      (DMARDs). METHODS: In this 12-month, double-blind, active-controlled and placebo
      controlled, phase 3 trial, we randomly assigned patients in a 2:2:2:1:1 ratio to
      receive one of the following regimens: tofacitinib at a 5-mg dose taken orally
      twice daily (107 patients), tofacitinib at a 10-mg dose taken orally twice daily
      (104), adalimumab at a 40-mg dose administered subcutaneously once every 2 weeks
      (106), placebo with a blinded switch to the 5-mg tofacitinib dose at 3 months
      (52), or placebo with a blinded switch to the 10-mg tofacitinib dose at 3 months
      (53). Placebo groups were pooled for analyses up to month 3. Primary end points
      were the proportion of patients who had an American College of Rheumatology 20
      (ACR20) response (>=20% improvement from baseline in the number of tender and
      swollen joints and at least three of five other important domains) at month 3 and
      the change from baseline in the Health Assessment Questionnaire-Disability Index
      (HAQ-DI) score (scores range from 0 to 3, with higher scores indicating greater
      disability) at month 3. RESULTS: ACR20 response rates at month 3 were 50% in the
      5-mg tofacitinib group and 61% in the 10-mg tofacitinib group, as compared with
      33% in the placebo group (P=0.01 for the comparison of the 5-mg dose with
      placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the rate was
      52% in the adalimumab group. The mean change in the HAQ-DI score was -0.35 in the
      5-mg tofacitinib group and -0.40 in the 10-mg tofacitinib group, as compared with
      -0.18 in the placebo group (P=0.006 for the comparison of the 5-mg dose with
      placebo; P<0.001 for the comparison of the 10-mg dose with placebo); the score
      change was -0.38 in the adalimumab group. The rate of adverse events through
      month 12 was 66% in the 5-mg tofacitinib group, 71% in the 10-mg tofacitinib
      group, 72% in the adalimumab group, 69% in the placebo group that switched to the
      5-mg tofacitinib dose, and 64% in the placebo group that switched to the 10-mg
      tofacitinib dose. There were four cases of cancer, three serious infections, and
      four cases of herpes zoster in patients who received tofacitinib during the
      trial. CONCLUSIONS: The efficacy of tofacitinib was superior to that of placebo
      at month 3 in patients with psoriatic arthritis who had previously had an
      inadequate response to conventional synthetic DMARDs. Adverse events were more
      frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Broaden
      ClinicalTrials.gov number, NCT01877668 .).

PMID- 29045213
TI  - Ventilation in Preterm Infants and Lung Function at 8 Years.

PMID- 29045214
TI  - Ventilation in Preterm Infants and Lung Function at 8 Years.

PMID- 29045215
TI  - Ventilation in Preterm Infants and Lung Function at 8 Years.

PMID- 29045216
TI  - Evaluation and Management of Lower-Extremity Ulcers.

PMID- 29045217
TI  - JAK Inhibitors Taking on Psoriatic Arthritis.

PMID- 29045218
TI  - The Power of Regret.

PMID- 29045219
TI  - Letter from the editor.

PMID- 29045220
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 29045223
TI  - RADIOLOGICAL SOCIETY OF NORTH AMERICA, INC: Proposed Amendments to the RSNA
      Bylaws November, 2017.

PMID- 29045221
TI  - Inverted Mucoid Impaction Signal in Allergic Bronchopulmonary Aspergillosis: Are
      We Calling a Spade a Big Spoon?

PMID- 29045224
TI  - Is "Segmentectomy" a Suitable Term to Use in Patients Undergoing Hepatic
      Segmental 90Y Radioembolization for the Treatment of Hepatocellular Carcinoma Up
      to 3 cm?

PMID- 29045225
TI  - Gadolinium-based Contrast Agents: The Plot Thickens.

PMID- 29045227
TI  - Limitations of Focused Assessment with Sonography in Trauma (FAST) Protocols in
      Transthoracic US.

PMID- 29045226
TI  - Science to Practice: Molecular-targeted Drug Delivery in Combination with
      Radiofrequency Ablation of Liver Cancer: A Magic Bullet?
AB  - In an effort to improve the technical success rates and clinical outcomes of
      radiofrequency (RF) ablation, Yan et al validated the use of a tumor-penetrating
      peptide and thermosensitive doxorubicin (DOX)-loaded nanoparticles in combination
      with RF ablation in a hepatocellular carcinoma mouse model. By achieving higher
      chemotherapeutic drug concentrations in target lesions, fewer toxic effects, and
      improved survival end points in an animal tumor model, the authors conclude that
      superior tumor treatment with RF ablation is possible when combined with
      molecular-targeted drug delivery systems.

PMID- 29045228
TI  - Guy Morgan Hicks, MD.

PMID- 29045229
TI  - Case 247: Jersey Finger of the Fifth Finger.
AB  - History A 34-year-old man without underlying medical conditions came to the
      emergency department for evaluation of persistent pain over the volar portion of
      his right fifth finger after a fall during a football match 3 days before. At
      physical examination, the injured finger was swollen and purple. Passive and
      active flexion of the proximal and distal interphalangeal joints were
      compromised, without interphalangeal instability. Radiography was performed in
      the emergency department, and the patient was released with a diagnosis of a
      fifth digit sprain. After the senior radiologist (V.M.C.) reviewed the
      radiographs, the patient was called back for assessment with ultrasonography (US)
      on the same day. US was performed with an Aplio 500 unit (Toshiba Medical
      Systems, Tokyo, Japan) using a multifrequency linear array 7.2-18.0-MHz PLT
      1204BX transducer focused at the level of the flexor tendon. The patient was
      sitting in front of the examiner, with the hand lying palm up on the examination
      bed. No abnormality was observed during color Doppler US.

PMID- 29045230
TI  - Case 251.

PMID- 29045231
TI  - A. Everette James, Jr, MD.

PMID- 29045232
TI  - Imaging Neoadjuvant Therapy Response in Breast Cancer.
AB  - The use of neoadjuvant systemic therapy in the treatment of breast cancer
      patients is increasing beyond the scope of locally advanced disease. Imaging
      provides important information in assessing response to therapy as a complement
      to conventional tumor measurements via physical examination. The purpose of this
      article is to discuss the advantages and limitations of current assessment
      methods, as well as review functional and molecular imaging approaches being
      investigated as emerging techniques for evaluating neoadjuvant therapy response
      for patients with primary breast cancer. (c) RSNA, 2017.

PMID- 29045233
TI  - The Current State of MR Imaging-targeted Biopsy Techniques for Detection of
      Prostate Cancer.
AB  - Systematic transrectal ultrasonography (US)-guided biopsy is the standard
      approach for histopathologic diagnosis of prostate cancer. However, this
      technique has multiple limitations because of its inability to accurately
      visualize and target prostate lesions. Multiparametric magnetic resonance (MR)
      imaging of the prostate is more reliably able to localize significant prostate
      cancer. Targeted prostate biopsy by using MR imaging may thus help to reduce
      false-negative results and improve risk assessment. Several commercial devices
      are now available for targeted prostate biopsy, including in-gantry MR imaging
      targeted biopsy and real-time transrectal US-MR imaging fusion biopsy systems.
      This article reviews the current status of MR imaging-targeted biopsy platforms,
      including technical considerations, as well as advantages and challenges of each
      technique. (c) RSNA, 2017.

PMID- 29045234
TI  - Diagnosis Please Certificates of Recognition Awarded to Three Individuals and to
      International and North American Radiology Resident Groups.

PMID- 29045235
TI  - The aqueous tuber extract of Pueraria tuberosa (Willd.) D.C. caused cytotoxic
      effect on HT 29 cell lines with down regulation of nuclear factor-kappa B (NF
      kappaB).
AB  - Background Pueraria tuberosa (Willd) D.C. (Fabaceae) tubers are already used in
      traditional medicine by Ayurvedic physicians for the management of fertility
      disorders, general weakness, and also as anti-ageing therapies. Other known
      pharmacological properties include: anti-hyperglycemics, hepatoprotective, anti
      hyperlipidemic, diuretic, nutritive, and anti-fertility agents in male rats.
      Methods The anti-proliferative effect of the aqueous tuberous root extract of
      Pueraria tuberosa on vascular smooth muscle cells (VSMCs) and Human Colorectal
      Adenocarcinoma Cell lines (HT-29) was investigated using the Cell Titer 96 MTT
      Proliferation Assay where the viable cells were seeded at a density of 5 * 104
      (100 uL/well). For VSMC, log concentrations of the extract at 200 and 800 ug/mL
      were added and incubated for 24 and 48 h time points. Incubation of the extract
      in the presence of vascular endothelial growth factor (VEGF) and ET-1 was also
      conducted at different times. Concentrations of the extract (200, 400 and 700
      ug/mL) were also added and incubated with the HT 29 cell lines for 24, 48 and 72
      h time points. The effect of the tuber aqueous extract of the plant on nuclear
      factor-kappaB (NF-kappaB) expression after 2 h was also carried out using
      immunoblotting technique. Results The result showed that after 24 h, the effect
      of the extract in the presence of the mitogens and on the VSMC was more of
      proliferation. However, at 48 h, the 200 ug/mL dose, both alone and in the
      presence of VEGF caused 11.1% and 25.9% decreases respectively, in cell
      proliferation. In the HT 29 cytotoxic study the 200 ug/mL concentration caused
      the greatest cytotoxic effect at 77.1% cell inhibition followed by 400 ug/mL
      concentration at 71.4% after 72 h. The immunoblotting assay showed a down
      regulation of NF-kappaB expressions with 0.7 ug/mL concentration showing the
      greatest effect. NF-kappaB, a pro-inflammatory agent is increasingly recognized
      as a crucial player in many steps of cancer initiation and progression.
      Conclusions It could therefore be concluded that the aqueous root extract of
      Pueraria tuberosa possesses cytotoxic effect and could serve as a lead compound
      for anticancer and anti-inflammatory agents.

PMID- 29045236
TI  - A microvascular compartment model validated using 11C-methylglucose liver PET in
      pigs.
AB  - The standard compartment model (CM) is widely used to analyse dynamic PET data.
      The CM is fitted to time-activity curves to estimate rate constants that describe
      the transport of a tracer between well-mixed compartments. The aim of this study
      was to develop and validate a more realistic microvascular compartment model
      (MCM) that includes capillary tracer concentration gradients, backflux from cells
      into the perfused capillaries and multiple re-uptakes during the passage through
      a capillary. The MCM incorporates only parameters with clear physiological
      meaning, it is easy to implement, and it does not require numerical solution. We
      compared the MCM and CM for the analysis of 3 min dynamic PET data of pig livers
      (N  =  5) following injection of 11C-methylglucose. During PET scans, the tracer
      concentrations in blood were measured in the abdominal aorta, portal vein and
      liver vein by manual sampling. We found that the MCM outperformed the CM and that
      dynamic PET data include information which cannot be extracted using standard CM.
      The MCM fitted dynamic PET data better than the CM (Akaike values were 46  +/-  4
      for best MCM fits, and 82  +/-  8 for best CM fits; mean  +/-  standard
      deviation) and extracted physiologically reasonable parameter estimates such as
      blood perfusion that were in agreement with independent measurements. The
      difference between model-independent perfusion estimates and the best MCM
      perfusion estimates was  -0.01  +/-  0.05 ml/ml/min, whereas the difference was
      0.30  +/-  0.13 ml/ml/min using the CM. In addition, the MCM predicted the time
      course of concentrations in the liver vein, a prediction fundamentally
      unobtainable using the CM as it does not return tracer backflux from cells to
      capillary blood. The results demonstrate the benefit of using models that include
      more physiology and that models including concentration gradients should be
      preferred when analysing the blood-cell exchange of any tracer in any capillary
      bed.

PMID- 29045237
TI  - Monoplane 3D-2D registration of cerebral angiograms based on multi-objective
      stratified optimization.
AB  - Registration of 3D pre-interventional to 2D intra-interventional medical images
      has an increasingly important role in surgical planning, navigation and
      treatment, because it enables the physician to co-locate depth information given
      by pre-interventional 3D images with the live information in intra-interventional
      2D images such as x-ray. Most tasks during image-guided interventions are carried
      out under a monoplane x-ray, which is a highly ill-posed problem for state-of-the
      art 3D to 2D registration methods. To address the problem of rigid 3D-2D
      monoplane registration we propose a novel multi-objective stratified parameter
      optimization, wherein a small set of high-magnitude intensity gradients are
      matched between the 3D and 2D images. The stratified parameter optimization
      matches rotation templates to depth templates, first sampled from projected 3D
      gradients and second from the 2D image gradients, so as to recover 3D rigid-body
      rotations and out-of-plane translation. The objective for matching was the
      gradient magnitude correlation coefficient, which is invariant to in-plane
      translation. The in-plane translations are then found by locating the maximum of
      the gradient phase correlation between the best matching pair of rotation and
      depth templates. On twenty pairs of 3D and 2D images of ten patients undergoing
      cerebral endovascular image-guided intervention the 3D to monoplane 2D
      registration experiments were setup with a rather high range of initial mean
      target registration error from 0 to 100 mm. The proposed method effectively
      reduced the registration error to below 2 mm, which was further refined by a fast
      iterative method and resulted in a high final registration accuracy (0.40 mm) and
      high success rate ([Formula: see text]96%). Taking into account a fast execution
      time below 10 s, the observed performance of the proposed method shows a high
      potential for application into clinical image-guidance systems.

PMID- 29045238
TI  - Hypergravity-induced multicellular spheroid generation with different
      morphological patterns precisely controlled on a centrifugal microfluidic
      platform.
AB  - In living tissue, cells exist in three-dimensional (3D) microenvironments with
      intricate cell-cell interactions. To model these cellular environments, numerous
      techniques for generating cell spheroids have been proposed and improved.
      However, previously reported methods still have limitations in uniformity,
      reproducibility, scalability, throughput, etc. Here, we present a centrifugal
      microfluidic-based spheroid (CMS) formation method for generating both co-culture
      and mono-culture 3D spheroids in a highly controlled manner. We designed
      circularly arrayed microwells to allow the even distribution of cells introduced
      at the center of a rotating platform and to provide identical hypergravity
      conditions at each well by the centrifugal forces generated. Compared with
      conventional well plate-based spheroid formation, the CMS formation method
      significantly promotes sphericity and consistency in both size and shape with
      high production yields. In addition to mono-culture spheroids, we successfully
      generated co-culture spheroids in concentric, Janus, and sandwich shapes using
      human adipose-derived stem cells and human lung fibroblasts, demonstrating the
      versatility of our CMS formation method. We believe that our new method for
      generating 3D spheroids will become one of the essential technologies in the
      field of 3D cell culture. We also expect that we are providing an innovative
      means to assess cellular responses, including cell motility under different
      hypergravity conditions.

PMID- 29045239
TI  - Contour propagation for lung tumor delineation in 4D-CT using tensor-product
      surface of uniform and non-uniform closed cubic B-splines.
AB  - A robust contour propagation method is proposed to help physicians delineate lung
      tumors on all phase images of four-dimensional computed tomography (4D-CT) by
      only manually delineating the contours on a reference phase. The proposed method
      models the trajectory surface swept by a contour in a respiratory cycle as a
      tensor-product surface of two closed cubic B-spline curves: a non-uniform B
      spline curve which models the contour and a uniform B-spline curve which models
      the trajectory of a point on the contour. The surface is treated as a deformable
      entity, and is optimized from an initial surface by moving its control vertices
      such that the sum of the intensity similarities between the sampling points on
      the manually delineated contour and their corresponding ones on different phases
      is maximized. The initial surface is constructed by fitting the manually
      delineated contour on the reference phase with a closed B-spline curve. In this
      way, the proposed method can focus the registration on the contour instead of the
      entire image to prevent the deformation of the contour from being smoothed by its
      surrounding tissues, and greatly reduce the time consumption while keeping the
      accuracy of the contour propagation as well as the temporal consistency of the
      estimated respiratory motions across all phases in 4D-CT. Eighteen 4D-CT cases
      with 235 gross tumor volume (GTV) contours on the maximal inhale phase and 209
      GTV contours on the maximal exhale phase are manually delineated slice by slice.
      The maximal inhale phase is used as the reference phase, which provides the
      initial contours. On the maximal exhale phase, the Jaccard similarity coefficient
      between the propagated GTV and the manually delineated GTV is 0.881 [Formula: see
      text] 0.026, and the Hausdorff distance is 3.07 [Formula: see text] 1.08 mm. The
      time for propagating the GTV to all phases is 5.55 [Formula: see text] 6.21 min.
      The results are better than those of the fast adaptive stochastic gradient
      descent B-spline method, the 3D  +  t B-spline method and the diffeomorphic
      demons method. The proposed method is useful for helping physicians delineate
      target volumes efficiently and accurately.

PMID- 29045240
TI  - Prediction of thromboembolic complications after liver resection for
      cholangiocarcinoma: is there a place for thromboelastometry?
AB  - : Postoperative venous thromboembolism has a poor prognosis in patients with
      cancer. We aimed to investigate the utility of thromboelastometry in detecting
      the risk of postoperative venous thromboembolism in patients with
      cholangiocarcinoma. We prospectively included patients submitted to liver
      resection for cholangiocarcinoma at our hospital between May 2011 and July 2014.
      Patients undergoing major hepatectomy for adult living donor transplantation in
      the same time period served as a control group. Thromboelastometry was performed
      before anesthesia. Postoperative venous thrombotic events were recorded in the 6
      months after surgery. Twenty-seven patients with cholangiocarcinoma and 17 living
      donor liver transplantation patients were included. Maximum clot firmness and its
      derivative parameter G, pointed to hypercoagulability in patients with
      cholangiocarcinoma, whereas all parameters were within normal ranges in controls.
      Six postoperative thrombotic events were recorded: four portal vein thrombosis
      and two deep venous thrombosis, all in patients with cholangiocarcinoma. Patients
      with cholangiocarcinoma who displayed thrombotic complications showed a
      nonsignificant trend to more pronounced hypercoagulability compared with those
      without. The results suggest that first, in patients with cholangiocarcinoma,
      despite standard thromboprophylaxis, thrombotic events remain a substantial
      problem, and, second, thromboelastometry may be useful in identifying patients
      with cholangiocarcinoma at risk of postoperative venous thromboembolism. Large
      prospective studies are warranted to confirm these results.

PMID- 29045241
TI  - Taking Assent to New Heights: A Case Report on Do-Not-Resuscitate Status in
      Pediatric Palliative Care Procedures.
AB  - Dying adolescents presenting for palliative procedures have complicated
      developmental and ethical issues, especially when reconsidering do-not
      resuscitate orders. Though the American Academy of Pediatrics has guidelines,
      there is limited information in the literature on how to take care of these
      patients. We describe the case of a 14-year-old patient presenting to the
      interventional radiology suite for management of superior vena cava syndrome. The
      patient's goals of treatment were elucidated through a comprehensive care team
      consisting of the procedural and oncology teams. Effective communication with the
      patient and family was paramount for success.

PMID- 29045243
TI  - Use of Ketamine in a Multimodal Analgesia Setting for Rapid Opioid Tapering in a
      Profoundly Opioid-Tolerant Patient: A Case Report.
AB  - Opioids are frequently used for the treatment of chronic pain, and patients
      taking high doses are at increased risk of complications and adverse opioid
      related events. Ketamine is appealing as an opioid adjunct because of its lack of
      respiratory depression and potential prevention of hyperalgesia and central
      sensitization. We present a case in which a ketamine infusion was utilized over a
      7-day period to provide rapid taper of a daily dose of 400 mg of morphine
      equivalents to less than one-third of that dose on discharge with unchanged pain
      levels and no symptoms of opioid withdrawal.

PMID- 29045242
TI  - Roles of the Microsurgeon and Anesthesiologist in the Treatment of Neonatal Upper
      Extremity Arterial Thrombosis: A Case Report.
AB  - We present a rare case of a newborn with spontaneous, noniatrogenic arterial
      thromboembolism in the right brachial artery and accompanying ischemic changes to
      the right upper extremity, who was successfully treated with microsurgical
      intervention and ultrasound-guided infraclavicular brachial plexus block with a
      continuous infusion of ropivacaine for 48 hours. This case report highlights the
      emerging role of both the microsurgeon and anesthesiologist in management of
      spontaneous neonatal arterial thromboembolism.

PMID- 29045244
TI  - Respectful Disposition After Miscarriage: Clinical Practice Recommendations.
AB  - Compassionate clinical practice guidelines for healthcare providers for
      respectful disposition after miscarriage are presented. When woven into the whole
      of a clinician's practice, these guidelines provide the framework for giving
      women and their families the care they want and deserve when experiencing
      miscarriage. Relying on theoretical concepts of personhood, place, and
      protection, care providers can assess the unique meaning a woman assigns to her
      early pregnancy loss and offer interventions that embrace the concept of
      respectful disposition. Respectful methods of disposition involve a continuum of
      care that shows respect for remains and relies on person-, family-, and culture
      centered nursing care. Policies, practices, and perspectives that flow from
      respectful disposition have women and families at their core and flexibility to
      cocreate care. This involves courage and competence. Several states have enacted
      fetal disposition laws, but these mandates are of questionable benefit because
      the expertise of healthcare leaders, nurses, physicians, chaplains, and other
      stakeholders must be involved in this sensitive and important area of care.
      Compassionate care cannot be legislated. We offer a practical approach to
      respectful disposition, including how to handle and prepare remains and examples
      of burial and memorial services, which will give clinicians the ability to
      respond empathetically and respectfully to the heart-rending plea of a woman who
      asks, "Where is my baby?"

PMID- 29045245
TI  - Newborn Safety Bundle to Prevent Falls and Promote Safe Sleep.
AB  - PURPOSE: At our Baby-Friendly USA hospital, with at least 80% of mothers
      breastfeeding and rooming-in, it is not uncommon for mothers to fall asleep in
      their hospital bed while feeding. The aim of this study was to develop a newborn
      infant safety bundle and evaluate its efficacy in helping reduce unsafe sleep
      situations while simultaneously preventing newborn falls. STUDY DESIGN AND
      METHOD: Data were collected in March 2015 using an infant at risk-to-fall
      instrument prior to nurses initiating the newborn infant safety bundle. The
      bundle included: (a) a parent safety agreement; (b) education, teach-back, and
      role modeling of safe sleep practices; and (c) implementation of a reporting and
      debriefing system for infant falls. All new mothers were eligible for inclusion.
      Data were collected over a random month every quarter for four quarters (through
      June 2016). RESULTS: Fourteen percent (n = 23) of babies born at the hospital in
      March 2015 were found to be exposed to risk-to-fall situations; over half of
      their mothers were found asleep and still holding the baby. Following bundle
      implementation, identified unsafe sleep situations during June 2015 to June 2016
      have trended down with no reports of an infant fall through May 2017. CLINICAL
      IMPLICATIONS: Increasing parental awareness, understanding, and participation in
      safe sleep practice creates and maintains a safer infant environment in the
      hospital setting.

PMID- 29045246
TI  - Hydralazine-Induced Autoimmune Hepatitis Precipitated by the Blood Transfusion.

PMID- 29045247
TI  - Factors Associated With Higher Caregiver Burden Among Family Caregivers of
      Elderly Cancer Patients: A Systematic Review.
AB  - BACKGROUND: Caring for elderly cancer patients may cause multidimensional burden
      on family caregivers. Recognition of factors associated with caregiver burden is
      important for providing proactive support to caregivers at risk. OBJECTIVE: The
      aim of this study was to identify factors associated with high caregiver burden
      among family caregivers of elderly cancer patients. METHODS: A systematic search
      of 7 electronic databases was conducted from database inception to October 2014.
      The identified studies were screened, and full text was further assessed. The
      quality of included studies was assessed using a checklist, and relevant data
      were extracted using a predeveloped data extraction form. Best-evidence synthesis
      model was used for data synthesis. RESULTS: The search yielded a total of 3339
      studies, and 7 studies involving 1233 family caregivers were included after
      screening and full assessment of 116 studies. Moderate evidence supported that
      younger caregivers, solid tumors, and assistance with patient's activities of
      daily living were significantly associated with high caregiver burden. Eighteen
      factors were supported by limited evidence, and 1 was a conflicting factor.
      CONCLUSIONS: The scientific literature to date proved that caregiver burden was
      commonly experienced by family caregivers of elderly cancer patients. The
      evidence indicated that family caregivers who were at younger age, caring for
      solid tumor patients, and providing assistance with patient's activities of daily
      living reported high caregiver burden. IMPLICATIONS FOR PRACTICE: The data
      provide evidence in identifying family caregivers at high risk of high caregiver
      burden. More high-quality studies are needed to clarify and determine the
      estimates of the effects of individual factors.

PMID- 29045248
TI  - The evolution of donation after circulatory death donor kidney repair in the
      United Kingdom.
AB  - PURPOSE OF REVIEW: The increasing reliance on marginal donors has driven research
      to investigate ways to repair and improve the quality of kidneys for
      transplantation. Normothermic perfusion technologies provide an opportunity for
      improved preservation, organ assessment and resuscitation/repair of damaged
      kidneys. This review describes the evolution of normothermic perfusion in kidney
      transplantation in the United Kingdom. RECENT FINDINGS: One hour of normothermic
      perfusion can be used to restore function and improve early graft function of
      extended criteria donor kidneys. A large multicentre trial is investigating the
      impact of normothermic perfusion on delayed graft function in a series of
      donation after circulatory death kidneys. Normothermic perfusion is also a
      platform for the delivery of therapies to the kidney to upregulate and modulate
      repair mechanisms or prevent injurious processes, such as activation of caspase-3
      with the delivery of caspase-3 targeted small interfering RNAs. Normothermic
      perfusion can also be used to assess the quality and anatomical structure of a
      kidney to judge suitability for transplantation. SUMMARY: Normothermic perfusion
      technology is a useful adjunct in kidney transplantation. It can improve early
      graft function by upregulating protective mechanisms. It also has the advantage
      of providing a functional assessment of the kidney and as a platform for the
      delivery of therapies or graft manipulation to target ischaemia reperfusion
      injury or the immune response. This technology can be used to expand the organ
      donor pool and prevent the unnecessary discard of kidneys.

PMID- 29045249
TI  - Inhaled Loxapine for Agitation in Intoxicated Patients: A Case Series.
AB  - OBJECTIVES: Episodes of agitation are frequent in intoxicated patients who have a
      substance use disorder, a psychiatric disorder or both (dual diagnosis). For
      managing the agitation, it is necessary to act promptly in a safe environment and
      addressing any underlying etiology. Inhaled loxapine improves symptoms of
      agitation in adults with psychiatric disorders (eg, schizophrenia) within 10
      minutes of administration. Recently, some reports have documented the usefulness
      of loxapine in dual diagnoses patients with agitation. However, the efficacy of
      loxapine in intoxicated patients has not been deeply addressed. METHODS: This
      report describes a case series of 12 patients (with addiction or dual disorder)
      who received inhaled loxapine for symptoms of psychomotor agitation during
      intoxication with different substances (eg, alcohol, cannabis, or cocaine) at 1
      center in Spain. RESULTS: Data from 12 patients were reviewed, 5 patients were
      attended at the emergency room, 4 at the addiction and dual diagnosis unit, and 3
      were treated during hospitalization for detoxification. All patients were under
      effects of substances. They had substance use disorder (including cannabis,
      cocaine, alcohol, hypnotics, and hallucinogens), and almost all (90%) presented 1
      or more psychiatric disorders. One dose of inhaled loxapine was effective in 9
      patients (75%), and in 3 patients, a second dose was required. Only mild
      dizziness was reported in 1 patient after the second dose. CONCLUSIONS: The acute
      agitation was effectively and quickly managed with inhaled loxapine in all
      intoxicated patients and enabled the appropriate clinical evaluation of the
      agitated state and the patient's management.

PMID- 29045250
TI  - Clinical decision-making for immunotherapy in metastatic renal cell carcinoma.
AB  - PURPOSE OF REVIEW: To review the treatment options in metastatic renal cell
      carcinoma (mRCC) in the light of new immunotherapy results. RECENT FINDINGS:
      Second-line treatment strategies for treatment of mRCC after progression on first
      line VEGF-targeted therapy have recently undergone a major change. Treatment
      guidelines currently recommend the use of either nivolumab, a programmed cell
      death 1 (PD-1) inhibitor, or cabozantinib, an inhibitor of multiple receptor
      tyrosine kinases, as preferred choices. Many factors influence the decision, but
      there are no predictive markers to guide the choice. It is not known at what
      stage, it is most appropriate to offer a checkpoint inhibitor (CPI) such as
      nivolumab; various factors influence this decision including the adverse event
      profile and the age of the patient. Recent positive first-line trial results with
      cabozantinib, with the combination of two CPIs (a PD-1-PD-L1 inhibitor and a CTLA
      4 inhibitor) and with a CPI with a VEGF inhibitor suggest that the first-line
      treatment paradigm will change rapidly, with consequential changes in second-line
      recommendations. SUMMARY: The treatment landscape in mRCC is changing rapidly and
      recent trial results suggest that CPI treatment combined with either another CPI
      or a VEGF inhibitor may be appropriate as first-line therapy in the future.

PMID- 29045251
TI  - Novel endoscopic visualization techniques for bladder cancer detection: a review
      of the contemporary literature.
AB  - PURPOSE OF REVIEW: To describe the principles of photodynamic diagnosis (PDD),
      narrow-band imaging (NBI) and Storz Professional Image Enhancement System (SPIES)
      techniques for the endoscopic management of nonmuscle-invasive bladder cancer
      (BCa) and to report their impact on clinical practice. RECENT FINDINGS: PDD is
      associated with an increased sensitivity for detecting BCa specifically carcinoma
      in situ (CIS). Moreover, PDD has been shown to lower recurrence rate in
      comparison with white-light cystoscopy. The impact on progression-free survival
      is still unclear yet. NBI and, more recently, SPIES are two novel imaging
      techniques that do not require preoperative instillation of photosensitizing
      agents. NBI seems to be associated with lower recurrence rates. Nevertheless,
      further trials are necessary to confirm these results, in particular in high-risk
      lesions and CIS. Randomized clinical trials addressing the clinical impact of
      SPIES are ongoing. SUMMARY: Novel endoscopic imaging techniques are useful
      diagnostic tools for evaluating BCa during cystoscopic diagnostic surveillance as
      well as during transurethral resection of the bladder. Although the standard of
      care remains white-light cystoscopy, these techniques provide higher sensitivity
      in detecting BCa especially CIS. The continued evidence also suggests that this
      increased detection leads to lower recurrence rates. The impact on progression
      and the cost-efficacy as well as selection remains to be refined.

PMID- 29045252
TI  - Altered gut microbiome composition in HIV infection: causes, effects and
      potential intervention.
AB  - PURPOSE OF REVIEW: Aim of this review is to summarize the alterations occurring
      in gut microbiome composition after HIV infection, and to underline how
      intestinal dysbiosis can affect immune homeostasis, immune recovery, and
      persisting immune activation under antiretroviral therapy (ART). Many
      interventions have been suggested, mostly with inconclusive results. RECENT
      FINDINGS: Recent evidence showed that gut microbiota from HIV-infected patients
      harbor reproducible differences compared to uninfected individuals. In this line,
      there is growing evidence that alterations in gut ecology during HIV infection
      correlate with persistence of immune defects and chronic inflammation. A reduced
      microbial diversity in feces of HIV-infected patients is highly associated with
      microbial translocation and monocyte activation markers; moreover, changes in
      mucosa-associated bacteria correlate with inflammation and T-cell activation.
      SUMMARY: Studying the human host-microbiota interaction suggests that the
      consequences of HIV infection on microbial composition can influence immune
      status in HIV patients. ART induces microbiome changes that are independent of
      HIV infection, and some imply that ART may enhance dysbiosis. Studies and trials
      evaluated the effects of administering probiotics and prebiotics, finding a
      potential benefit on inflammation markers and immune cell activation. Emerging
      data on fecal microbial transplantation need to be assessed with further studies.

PMID- 29045254
TI  - Nutritional interventions in sarcopenia: where do we stand?
AB  - PURPOSE OF REVIEW: To document recent evidence regarding the role of nutrition as
      an intervention for sarcopenia. RECENT FINDINGS: A review of seven randomized
      controlled trials (RCTs) on beta-hydroxy-beta-methylbutyrate (HMB) alone on
      muscle loss in 147 adults showed greater muscle mass gain in the intervention
      group, but no benefit in muscle strength and physical performance measures. Three
      other review articles examined nutrition and exercise as combined intervention,
      and suggest enhancement of benefits of exercise by nutrition supplements (energy,
      protein, vitamin D). Four trials reported on nutrition alone as intervention,
      mainly consisting of whey protein, leucine, HMB and vitamin D, with variable
      results on muscle mass and function. Four trials examined the combined effects of
      nutrition combined with exercise, showing improvements in muscle mass and
      function. SUMMARY: To date, evidence suggests that nutrition intervention alone
      does have benefit, and certainly enhances the impact of exercise. Nutrients
      include high-quality protein, leucine, HMB and vitamin D. Long-lasting impact may
      depend on baseline nutritional status, baseline severity of sarcopenia, and long
      lasting adherence to the intervention regime. Future large-scale multicentered
      RCTs using standardized protocols may provide evidence for formulating guidelines
      on nutritional intervention for sarcopenia. There is a paucity of data for
      nursing home populations.

PMID- 29045253
TI  - Gut microbial diversity in HIV infection post combined antiretroviral therapy: a
      key target for prevention of cardiovascular disease.
AB  - PURPOSE OF REVIEW: Although the HIV-infected population is living longer and
      getting older under current treatment regimens, significant challenges arise for
      health management as the infection is associated with various premature aging
      phenotypes, particularly increased incidence of cardiovascular diseases (CVDs).
      Here we review the current understanding of HIV-related gut dysbiosis in
      association with CVD and advances in clinical trials aiming to restore gut
      microbial diversity. RECENT FINDING: Identification of a unique signature for gut
      dysbiosis in HIV infection between different cohorts remains challenging.
      However, low diversity of microbiota combined with the outgrowth of pathogenic
      bacterial species together with dysregulated metabolic pathways have been linked
      to compromised gut immunity, bacterial translocation and systemic inflammation,
      hence higher CVD risk among different cohorts. Data from recent clinical trials
      aiming to evaluate the tolerability and efficacy of probiotics in treated HIV+
      patients are promising and support a significant increase in microbiota diversity
      and reduction of systemic inflammation. However, the impact of these microbial
      and immunological corrections on the prevalence of CVD in HIV+ patients remains
      unclear. SUMMARY: Positive immunological outcomes following enrichment of the gut
      microbial diversity have been documented, and further trials are in progress to
      evaluate the range of patients, with different immunological backgrounds, who
      might benefit from these treatments.

PMID- 29045255
TI  - Listening to Relaxing Music Improves Physiological Responses in Premature
      Infants: A Randomized Controlled Trial.
AB  - BACKGROUND: Premature infants are exposed to high levels of noise in the neonatal
      intensive care unit (NICU). PURPOSE: This study evaluated the effect of a
      relaxing music therapy intervention composed by artificial intelligence on
      respiratory rate, systolic and diastolic blood pressure, and heart rate. METHODS:
      A double-blind, randomized, controlled trial was conducted in the NICUs of 2
      general public hospitals in Andalusia, Spain. Participants were 17 healthy
      premature infants, randomly allocated to the intervention group or the control
      group (silence) at a 1:1 ratio. To be included in the study, the subjects were to
      be 32 to 36 weeks of gestation at birth (M= 32.33; SD = 1.79) and passed a
      hearing screening test satisfactorily. The intervention lasted 20 minutes, 3
      times a day for 3 consecutive days, while infants were in the incubator. Infants'
      heart rate, respiratory rate, and blood pressure were assessed before and after
      each intervention session. RESULTS: After each session, the respiratory rate
      decreased in the experimental group (main between-groups effect (F1,13 = 6.73, P
      = .022, etapartial = 0.34). Across the sessions, the heart rate increased in the
      control group (main between-groups effect, F1,11 = 5.09, P = .045, etapartial =
      0.32). IMPLICATIONS FOR RESEARCH: Future studies can use this music intervention
      to assess its potential effects in premature infants. IMPLICATIONS FOR PRACTICE:
      Nurses can apply the relaxing music intervention presented in this study to
      ameliorate the impact of the stressful environment on premature infants.

PMID- 29045256
TI  - A Quality Improvement Initiative to Increase Scoring Consistency and Accuracy of
      the Finnegan Tool: Challenges in Obtaining Reliable Assessments of Drug
      Withdrawal in Neonatal Abstinence Syndrome.
AB  - BACKGROUND: Current practice for diagnosing neonatal abstinence syndrome and
      guiding pharmacological management of neonatal drug withdrawal is dependent on
      nursing assessments and repeated evaluation of clinical signs. PURPOSE: This
      single-center quality improvement initiative was designed to improve accuracy and
      consistency of Finnegan scores among neonatal nurses. METHODS: One-hundred
      seventy neonatal nurses participated in a single-session withdrawal-assessment
      program that incorporated education, scoring guidelines, and a restructured
      Finnegan scale. Nurses scored a standardized video-recorded infant presenting
      with opioid withdrawal before and after training. RESULTS: Nearly twice as many
      nurses scored at target (Finnegan score of 8) posttraining (34.7%; mean error =
      0.559, SD = 1.4) compared with pretraining (18.8%; mean error = 1.31, SD = 1.95;
      Wilcoxon, P < .001). Finnegan scores were significantly higher than the target
      score pretraining (mean = 9.31, SD = 1.95) compared with posttraining (mean =
      8.56, SD = 1.40, Wilcoxon P < .001); follow-up assessments reverted to
      pretraining levels (mean = 9.16, SD = 1.8). Score dispersion was greater
      pretraining (variance 3.80) compared with posttraining (variance 1.96; Kendall's
      Coefficient, P < .001) largely due to score disparity among central nervous
      system symptomology. IMPLICATIONS FOR PRACTICE: Education, clinical guidelines,
      and a restructured scoring tool increased consistency and accuracy of infant
      withdrawal-assessments among neonatal nurses. However, more than 60% of nurses
      did not assess withdrawal to the target score immediately following the training
      period and improvements did not persist over time. IMPLICATIONS FOR RESEARCH:
      This study highlights the need for more objective tools to quantify withdrawal
      severity given that assessments are the primary driver of pharmacological
      management in neonatal drug withdrawal.Video Abstract available at
      https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

PMID- 29045257
TI  - Fathers: The Lost Ring in the Chain of Family-Centered Care: A Phenomenological
      Study in Neonatal Intensive Care Units of Iran.
AB  - BACKGROUND: The basic principles of family-centered care in neonatal intensive
      care unit (NICU) include the unlimited presence of parents and their
      participation in infant's care. Nurses play a central role in encouraging
      parental attachment with their infant. PURPOSE: This study was carried out with
      the aim of understanding NICU nurses' lived experiences of family participation
      in family-centered care. METHODS: This interpretative phenomenological study was
      conducted on the basis of Heideggerian philosophy. The data were collected using
      semistructured interviews and field notes and analyzed through the 7-stage
      Diekelmann, Allen, and Tanner approach. FINDINGS: Two overarching themes emerged
      including "mother's centrality in the care chain" and "fathers; the lost ring in
      the care chain" each of which consisted of 3 and 4 subthemes, respectively.
      Interviews indicated that in Iran's NICUs, conditions for the presence of parents
      were appropriate for the mothers and they were encouraged to engage in family
      centered care but the fathers' participation was limited due to traditional
      attitudes, cultural-religious background, and difficulties relating to the
      hospitals' organizational rules. IMPLICATIONS FOR PRACTICE: Fathers'
      participation in family-centered care seems to be enhanced through providing
      facilities, altering the organizational rules, attempting to modify traditional
      social attitudes, and educating parents and nurses. IMPLICATIONS FOR RESEARCH:
      Future research should explore the experience of mothers and fathers of infants
      in NICU in Iran to achieve a comprehensive understanding of their role in family
      centered care.

PMID- 29045258
TI  - Early Behavioral Risks of Childhood and Adolescent Daytime Urinary Incontinence
      and Nocturnal Enuresis.
AB  - OBJECTIVE: To investigate whether infant temperament and childhood internalizing,
      externalizing, and inattention symptoms increase the likelihood of daytime
      urinary incontinence or nocturnal enuresis at 10 years and adolescence (11.9-17.8
      years). METHOD: Data were from a longitudinal cohort of 1119 healthy Chilean
      children. We assessed behavioral symptoms at infancy, 5 years, and 10 years and
      their relationship with subsequent daytime urinary incontinence and nocturnal
      enuresis. RESULTS: Daytime urinary incontinence and nocturnal enuresis occurred
      in, respectively, 3.3% and 11.4% at 10 years and 1.1% and 2.7% at adolescence.
      Difficult infant temperament was associated with increased odds of 10-year
      daytime urinary incontinence. Inattention at 5 years was associated with
      increased odds for nocturnal enuresis at 10 years and adolescence. Internalizing
      and externalizing symptoms at 5 years were associated with increased odds of 10
      year daytime urinary incontinence and nocturnal enuresis. Internalizing and
      externalizing symptoms at 10 years were associated with adolescent nocturnal
      enuresis. CONCLUSION: Temperament and internal/externalizing symptoms may be risk
      factors for school-age and adolescent urinary incontinence.

PMID- 29045260
TI  - Encopresis Plus?
AB  - CASE: Dexter is a 12-year-old boy who presents with his maternal grandmother for
      follow-up to primary care for secondary encopresis. Dexter presented, 18 months
      ago, with a 3-month history of secondary encopresis. At that time, a
      comprehensive assessment revealed functional constipation resulting in
      encopresis. Dexter's symptoms resolved with a combination of medication
      management and behavioral strategies; laxatives were discontinued 12 months
      ago.Dexter's grandmother reports that for the past 6 months, her grandson
      developed encopresis once again. However, she notes that, although Dexter had
      small-volume episodes of soiling in the past, he is now passing fully formed
      stools into his underwear. These episodes usually occur once a day, either at
      home or at school. Frustrated, Dexter's grandmother has transitioned him to adult
      diapers.Dexter denies hematochezia, pain, dysuria, hematuria, urinary
      incontinence, dietary changes, or weight loss. He passes soft stool in his
      underwear once daily without blood or pain. When interviewed alone, Dexter denies
      drug use, depression, or significant social stressors. Surprisingly, he seems
      unconcerned about depression, drugs and social stress, and frequently laughs when
      discussing them. His physical examination, including a rectal examination, is
      normal.Dexter's medical history is notable for attention-deficit hyperactivity
      disorder, treated with stimulant medication. He was toilet trained at 3 years
      without any difficulty. He lives with his grandmother, who is his legal guardian;
      his mother has chronic mental health problems and substance abuse. Dexter
      maintains regular contact with his mother and reports that their relationship is
      positive.Dexter's grandmother is extremely distressed by his current presentation
      and notably, Dexter is not. What would you do next?

PMID- 29045262
TI  - IBD LIVE Series-Case 8: Treatment Options for Refractory Esophageal Crohn's
      Disease and Hidradenitis Suppurativa: ERRATUM.

PMID- 29045261
TI  - Incidence and Outcomes of Central Venous Catheter-related Blood Stream Infection
      in Patients with Inflammatory Bowel Disease in Routine Clinical Practice Setting.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) occasionally require
      central venous catheter (CVC) placement to support a therapeutic plan. Given that
      CVC can predispose patients to infection, this investigation was undertaken to
      assess the incidence, risk factors, and outcomes of CVC-related blood stream
      infection (CRBSI) in patients with IBD during routine clinical practice. METHODS:
      Data were compiled using retrospective chart reviews of 1367 patients treated at
      our IBD center between 2007 and 2012 during routine clinical practice. Among the
      1367 patients, 314 who had received CVC placements were included. Patients with
      positive blood culture were considered as "definite" CRBSI, whereas "possible"
      CRBSI was defined as patients in whom fever alleviated within 48 hours post-CVC
      without any other infection. Patients' demographic variables including age, body
      mass index, serum albumin, duration of CVC placement, use of antibiotics,
      medications for IBD, and perioperative status between CRBSI and non-CRBSI
      subgroups were compared by applying a multivariate Poisson logistic regression
      model. RESULTS: Among the 314 patients with CVC placement, there were 83 CRBSI
      cases (26.4%). The average time to the onset of CRBSI was 22.5 days (range 4-105
      days). The jugular vein access was found to be the most serious risk of CRBSI
      (risk ratio 2.041 versus subclavian vein). All patients with CRBSI fully
      recovered. CONCLUSIONS: In this investigation, regardless of the patients'
      demographic features including immunosuppressive therapy, up to 30% of febrile
      IBD patients with CVC showed CRBSI. It is believed that CVC placement per se is a
      risk of CRBSI in patients with IBD.

PMID- 29045263
TI  - Diagnosis of Axillary Web Syndrome in Patients After Breast Cancer Surgery:
      Epidemiology, Risk Factors, and Clinical Aspects: A Prospective Study.
AB  - OBJECTIVES: Axillary web syndrome (AWS) is a complication after breast cancer
      surgery associated with the axillary approach. We defined a diagnosis tool as
      well as evaluated cord frequency, characteristics, and risk factors. METHODS: A
      prospective cohort study of 173 women followed-up at Breast Diseases Division of
      Universidade Federal de Sao Paulo between July 2014 and September 2015 was
      established as an evaluation protocol to diagnose AWS. Sociodemographic status,
      anthropometric values, range of motion, comorbidities, pain, cord frequency, and
      characteristics (localization, number, palpable, and/or visible) among other data
      were collected at different time points before and after surgery. RESULTS: The
      majority of the cords appeared by the seventh day (66.1%), and the total
      incidence of the cords was 90.9% at the 180th day. The axilla was the place for
      80% of the occurrence of AWS, and >70% of the cords were palpable. Flexion and
      abduction of the shoulder showed reduced range of motion. Pain was present in
      39.7% of the patients. Lymphadenectomy as well as hypertension were associated
      with increased risk of cord development; diabetes was associated with a decreased
      risk. CONCLUSIONS: The evaluation protocol applied here showed a high incidence
      of AWS, with palpable cords more frequent than visible ones. The significance of
      hypertension and diabetes mellitus as risk factors for cord development in AWS
      should be evaluated in future studies. The evaluation protocol developed in this
      study seems to be of great importance for early detection of AWS and could also
      be valuable for future treatment planning.

PMID- 29045264
TI  - Patterns of Failure in Patients With Adult Medulloblastoma Presenting Without
      Extraneural Metastasis.
AB  - OBJECTIVES: The objective of this study is to evaluate long-term outcomes,
      specifically patterns of tumor recurrence, in patients with adult medulloblastoma
      treated with radiotherapy. METHODS: We recorded outcomes of 28 (median age, 25 y)
      patients 18 years old or above with M0 to M3 medulloblastoma treated between 1971
      and 2012. Among them, 61% had standard-risk disease. All received craniospinal
      irradiation with a posterior fossa boost. Median dose to the craniospinal axis
      was 36 Gy. Median total dose to the primary site was 55.9 Gy and 46% received
      chemotherapy. RESULTS: Median follow-up among survivors was 14.2 years. At 5 and
      10 years, local control was 80% and 73%, overall survival was 71% and 59%, cause
      specific survival was 71% and 63%, and freedom from progression was 68% and 59%.
      Tumors recurred in 11 patients (39%); median time to recurrence was 2.4 years,
      and 82% of recurrences developed in patients with standard-risk disease. Of the
      recurrences, 55% involved the primary site; 36% were bone metastases without
      neural axis recurrence. There were no isolated recurrences in the spinal canal or
      ventricular system outside of the posterior fossa. CONCLUSION: The primary site
      is the main site of medulloblastoma recurrence, with isolated bone metastases
      more common in adults than children. Our results prompt us to consider 4
      modifications to our treatment approach with adults who present with
      medulloblastoma: (1) initial staging to include PET or bone scan; (2)
      radiotherapy dose to the primary site of 59.4 Gy; (3) chemotherapy during and/or
      following radiotherapy in medically fit patients; (4) follow-up to include PET or
      bone scan twice a year for 3 years.

PMID- 29045265
TI  - Dose Escalation Study of Concurrent Chemoradiotherapy With the Use of Involved
      field Conformal Radiotherapy and Accelerated Hyperfractionation in Combination
      With Cisplatin and Vinorelbine Chemotherapy for Stage III Non-small Cell Lung
      Cancer: The Final Report.
AB  - OBJECTIVES: A phase I study to determine a recommended dose of thoracic
      radiotherapy using accelerated hyperfractionation for unresectable non-small cell
      lung cancer was conducted. MATERIALS AND METHODS: We used chemotherapy of a
      cisplatin doublet and 2 dose levels of radiation with accelerated
      hyperfractionation. The radiation dose levels were: a total dose of 60 Gy in 40
      fractions at level 1, and 66 Gy in 44 fractions at level 2. Eligible patients
      with unresectable stage III non-small cell lung cancer received cisplatin and
      vinorelbine. Radiation therapy started on day 2 of chemotherapy and was delivered
      twice daily for 5 days a week. RESULTS: Total 12 patients were enrolled, with 6
      patients each at dose levels 1 and 2. Dose-limiting toxicity was noted in 2
      patients at level 1; one patient had grade 3 febrile neutropenia and the other
      patient had grade 3 esophagitis. No dose-limiting toxicity was noted in the 6
      patients at level 2. Grade 3 to 4 leukopenia, neutropenia, and anemia were noted
      in 11 (92%), 9 (75%), and 8 (67%) of the total 12 patients, respectively. Grade 3
      anorexia and infection were noted in 2 patients (17%) at each level. Grade 3
      nausea, fatigue, esophagitis, and febrile neutropenia were noted in 1 patient
      (8%) at each level. The response rate in the total 12 patients was 83.3%. The
      median progression-free survival time and the median overall survival time were
      10.7 and 24.2 months, respectively. CONCLUSIONS: Sixty-six gray in 44 fractions
      is the recommended dose for the following phase II study.

PMID- 29045266
TI  - Travel Distance as a Barrier to Receipt of Adjuvant Radiation Therapy After
      Radical Prostatectomy.
AB  - OBJECTIVES: Following radical prostatectomy (RP), adjuvant radiation therapy (RT)
      decreases biochemical recurrence and potentially improves metastasis-free and
      overall survival for patients with high-risk pathologic features. Since adjuvant
      RT typically occurs daily over several weeks, the logistical challenges of
      extensive traveling may be a significant barrier to its use. We examined the
      association between distance to treatment facility and use of adjuvant RT.
      MATERIALS AND METHODS: We identified 97,568 patients in the National Cancer
      Database diagnosed from 2004 through 2011 with cT1-4N0-xM0-x prostate cancer and
      found to have high-risk pathologic features (pT3-4 stage and/or positive surgical
      margins) at RP. Multivariable logistic regression adjusting for sociodemographic
      and clinicopathologic factors was used to examine the association between travel
      distance and receipt of adjuvant RT, defined as radiotherapy initiated within 12
      months after RP. RESULTS: Overall, 10.6% (10,346) of the study cohort received
      adjuvant RT. On multivariable analysis, increasing travel distance was
      significantly associated with decreased use of adjuvant RT, with adjusted odds
      ratios of 1.0 (reference), 0.67, 0.46, 0.39, and 0.32 (all P<0.001) and
      prevalence of use at 12.6%, 8.8%, 6.3%, 4.9%, and 3.7% for patients living
      <=25.0, 25.1 to 50.0, 50.1 to 75.0, 75.1 to 100.0, and >100.0 miles away,
      respectively. CONCLUSIONS: Increasing travel distance was strongly associated
      with decreased use of adjuvant RT in this national cohort of postprostatectomy
      patients with high-risk pathologic features. These results strongly suggest that
      the logistical challenges of extensive travel are a significant barrier to the
      use of adjuvant RT. Efforts aimed at improving access to radiotherapy and
      reducing treatment time are urgently needed.

PMID- 29045267
TI  - The Prevalence and Investigation of Risk Factors of Oral Mucositis in a Pediatric
      Oncology Inpatient Population; a Prospective Study.
AB  - BACKGROUND: Oral mucositis can be a frequent and severe complication of
      chemotherapy in children. It can result in pain, infection, depression, prolonged
      admission, treatment delays, increase in patient morbidity, and increased costs.
      AIM: To record the prevalence and severity of oral mucositis among inpatients and
      explore the relationship of risks factors and the development of oral mucositis.
      DESIGN: During an 18-month period 643 clinical inpatient assessments were
      completed on 73 children who were admitted and had received chemotherapy in the
      last 14 days. RESULTS: There were 43 episodes of oral mucositis in 31 children;
      42.5% of the inpatient population. World Health Organization assessment
      identified 32.6% of episodes were grade 1, 34.9% grade 2, 14.0% grade 3, and
      18.6% grade 4. Analysis revealed significant associations between patient
      diagnosis (P<0.0001), chemotherapy cycles (P<0.0001), day 8 and 9 of the
      chemotherapy cycle (P<0.05), and neutropenia (P<0.0001) and oral mucositis.
      Children had increased length of admission with increasing severity of oral
      mucositis (P=0.0005). CONCLUSIONS: The prevalence of oral mucositis was 42.5%
      among inpatients and admission length was increased with increasing severity.
      Patient diagnosis, chemotherapy treatment block, day of chemotherapy cycle, and
      neutropenic status were shown to influence the risk of developing oral mucositis.

PMID- 29045268
TI  - Early Nutrition Intervention Attenuates Weight Gain for Pediatric Acute
      Lymphoblastic Leukemia Patients in Maintenance Therapy.
AB  - Obesity following treatment of pediatric acute lymphoblastic leukemia (ALL) has
      become a significant long-term concern. Excessive weight gain often occurs during
      treatment, particularly during induction and the first 6 months of maintenance
      therapy, and it may be potentially modifiable. This retrospective study aimed to
      evaluate the impact of an early, 3-visit nutrition intervention on weight gain
      during maintenance therapy in ALL patients. Medical records of the intervention
      group were compared with historical controls who were treated on the same ALL
      treatment protocols during an earlier time period. Anthropometrics were collected
      throughout intensive therapy and at every monthly visit during the first 12
      months of maintenance therapy. In total, 67 patients were evaluated (33 in the
      intervention group and 34 in the control group). After controlling for
      significant predictors of body mass index (BMI) z-scores in maintenance therapy
      including higher BMI at diagnosis and weight gain throughout intensive therapy
      the intervention group demonstrated more controlled weight gain during
      maintenance therapy (P<0.0001). A 3-visit nutrition intervention was effective in
      attenuating weight gain trends during ALL maintenance therapy.

PMID- 29045270
TI  - Macroglossia During Awake Craniotomy: A Near Miss.

PMID- 29045269
TI  - CHOROIDEREMIA ASSOCIATED WITH A NOVEL SYNONYMOUS MUTATION IN GENE ENCODING REP-1.
AB  - PURPOSE: To report a novel synonymous mutation in CHM and the associated
      phenotype in an affected man and carrier mother. METHODS: Case report. RESULTS: A
      34-year-old man with a long history of progressive night blindness and visual
      field constriction was diagnosed with choroideremia based on ocular examination
      and multimodal retinal imaging. Extensive chorioretinal degeneration was noted on
      spectral domain optical coherence tomography and fundus autofluorescence imaging.
      Candidate CHM gene sequencing revealed a hemizygous c.1359C>T, p.(S453S) variant.
      This variant was heterozygous in the mother of the proband who exhibited the
      classic carrier phenotype of choroideremia on fundus autofluorescence imaging.
      CONCLUSION: A novel c.1359C>T, p.(S453S) variant in CHM is the first-identified
      synonymous mutation associated with disease manifestation in an affected man and
      carrier phenotype in a heterozygous mother.

PMID- 29045271
TI  - Rhabdomyosarcoma cells are susceptible to cell death by LDK378 alone or in
      combination with sorafenib independently of anaplastic lymphoma kinase status.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is often
      overexpressed in rhabdomyosarcoma (RMS). However, its oncogenic and functional
      role in RMS remains unclear. Therefore, we investigated the antitumor activity of
      LDK378 (ceritinib), a new second-generation ALK inhibitor approved for patients
      with ALK-positive non-small-cell lung cancers. Here, we report that LDK378
      reduces cell viability and induces cell death in RMS cell lines at low micromolar
      IC50 concentrations irrespective of ALK expression levels or phosphorylation
      status. Compared with Karpas 299 non-Hodgkin's lymphoma cells carrying the NPM
      ALK fusion gene, RMS cell lines proved to be far less sensitive to LDK378. The
      broad-range caspase inhibitor zVAD.fmk significantly protects RMS cells from
      LDK378-mediated cell death, indicating that LDK378 induces caspase-dependent
      apoptotic cell death. Before the onset of apoptosis, LDK378 reduces
      phosphorylation of AKT, S6 ribosomal protein, STAT3 and - to a lesser extent -
      phosphorylation of ERK, showing that it suppresses key survival pathways.
      Importantly, we identify a synergistic induction of cell death by combining
      subtoxic concentrations of LDK378 with the multitargeting kinase inhibitor
      sorafenib. Calculation of the combination index confirmed that this interaction
      is synergistic. Also, LDK378 cooperates with sorafenib to significantly reduce
      colony formation of RMS cells, showing that this combination affects long-term
      clonogenic growth. In conclusion, LDK378 induces caspase-dependent apoptotic cell
      death in RMS cells independent of their ALK status and synergizes at subtoxic
      concentrations with sorafenib to induce cell death. These findings have important
      implications for the use of LDK378 in RMS.

PMID- 29045272
TI  - Palliative Nursing for Cancer Patients as an Abstract Concept: A Hermeneutic
      Study.
AB  - BACKGROUND: Understanding the outcomes of palliative care (PC) that is provided
      to patients with cancer is necessary. PURPOSE: The aim of this study was to
      explore the lived experiences of Iranian nurses with regard to PC outcomes in
      cancer patients. METHODS: This hermeneutic study interviewed 14 nurses to
      understand their lived experiences with regard to PC outcomes in cancer patients.
      A seven-stage process of data analysis was employed. RESULTS: One constitutive
      pattern "palliative nursing for cancer patients is an abstractive concept" and
      the two associated themes of "providing excellent PC" and "PC as an alarm" were
      identified. Providing excellent PC had two subthemes: being a unique nurse and
      experiencing the humanistic approach to caring. PC as an alarm also had two
      subthemes: caring-related concerns and challenging issues caused by caring.
      CONCLUSIONS: The findings provide a deeper understanding of the nursing
      experience with regard to PC outcomes in cancer patients.

PMID- 29045273
TI  - OneFlorida Clinical Research Consortium: Linking a Clinical and Translational
      Science Institute With a Community-Based Distributive Medical Education Model.
AB  - PROBLEM: Developing a national pragmatic clinical trial infrastructure is central
      to understanding the effectiveness of interventions applied under usual
      conditions and where people receive health care. To address this challenge, three
      Florida universities-the University of Florida Clinical and Translational Science
      Institute, Florida State University (with its community-based distributive
      medical education model), and the University of Miami-created (2010-2013) a
      statewide consortium, the OneFlorida Clinical Research Consortium, to support the
      conduct of pragmatic clinical trials and provide mentored research experiences
      for medical and graduate students in real-world practice settings. APPROACH:
      OneFlorida has four programs, which report to a steering committee with
      membership from each partner, community members, and the state Medicaid agency
      and Department of Health to ensure shared governance. The Clinical Research
      Program provides support to conduct research in the network and uses champions to
      engage community clinicians. The Citizen Scientist Program has community members
      who provide input on health topics of importance to them, study design,
      recruitment and retention strategies, and the interpretation of findings. The
      Data Trust Program contains electronic health record and health care claims data
      for 10.6 million Floridians. The Minority Education Program, in collaboration
      with three historically black colleges and universities, offers minority junior
      faculty mentoring in pragmatic clinical trials and implementation science.
      OUTCOMES: OneFlorida has implemented 27 studies with diverse patient populations
      and in diverse community practice settings. NEXT STEPS: To identify evidence
      based best practices from the clinical trials conducted in the network, foster
      their implementation, and expand research training opportunities.

PMID- 29045274
TI  - Recruiting American Indian/Alaska Native Students to Medical School: A Multi
      Institutional Alliance in the U.S. Southwest.
AB  - PROBLEM: Despite national efforts to diversify the physician workforce, American
      Indian/Alaska Native (AI/AN) individuals have the least representation of all
      major racial and ethnic groups. Limited resources at state medical schools
      present institution-level recruitment challenges. Unified efforts to engage AI/AN
      students in premedical education activities are needed. APPROACH: The medical
      schools at the Universities of Arizona (Phoenix and Tucson), Colorado, New
      Mexico, and Utah identified a collective need to increase student diversity,
      particularly with regard to AI/AN students. The schools partnered with the
      Association of American Indian Physicians to support AI/AN students applying to
      medical school and to grow the overall AI/AN applicant pool. Each year from 2011
      to 2016, these institutions hosted a two-day preadmissions workshop (PAW) to
      prepare participants for applying to medical school. OUTCOMES: From 2011 to 2016,
      130 AI/AN students participated in the PAWs. Of these, 113 were first-time
      attendees, 15 participated on two separate occasions, and 1 participated on three
      separate occasions. Nineteen (21%) of the 90 first-time participants from 2011 to
      2015 matriculated to a U.S. medical school in the past five years. Twenty-two of
      23 participants (96% response rate) in 2016 responded to the postworkshop survey.
      Results indicated that interview preparation, individual consultation, and
      writing preparation ranked as the three most beneficial sessions/activities. NEXT
      STEPS: Standardized evaluation of future PAWs will identify best practices for
      recruiting AI/AN students to medical school, and future initiatives will include
      more robust measures of success.

PMID- 29045275
TI  - Medical Education in Decentralized Settings: How Medical Students Contribute to
      Health Care in 10 Sub-Saharan African Countries.
AB  - PURPOSE: African medical schools are expanding, straining resources at tertiary
      health facilities. Decentralizing clinical training can alleviate this tension.
      This study assessed the impact of decentralized training and contribution of
      undergraduate medical students at health facilities. METHOD: Participants were
      from 11 Medical Education Partnership Initiative-funded medical schools in 10
      African countries. Each school identified two clinical training sites-one rural
      and the other either peri-urban or urban. Qualitative and quantitative data
      collection tools were used to gather information about the sites, student
      activities, and staff perspectives between March 2015 and February 2016.
      Interviews with site staff were analyzed using a collaborative directed approach
      to content analysis, and frequencies were generated to describe site
      characteristics and student experiences. RESULTS: The clinical sites varied in
      level of care but were similar in scope of clinical services and types of
      clinical and nonclinical student activities. Staff indicated that students have a
      positive effect on job satisfaction and workload. Respondents reported that
      students improved the work environment, institutional reputation, and introduced
      evidence-based approaches. Students also contributed to perceived improvements in
      quality of care, patient experience, and community outreach. Staff highlighted
      the need for resources to support students. CONCLUSIONS: Students were seen as
      valuable resources for health facilities. They strengthened health care quality
      by supporting overburdened staff and by bringing rigor and accountability into
      the work environment. As medical schools expand, especially in low-resource
      settings, mobilizing new and existing resources for decentralized clinical
      training could transform health facilities into vibrant service and learning
      environments.

PMID- 29045276
TI  - Impact of Required Versus Self-Directed Use of Virtual Patient Cases on Clerkship
      Performance: A Mixed-Methods Study.
AB  - PURPOSE: To explore how students use and benefit from virtual patient cases
      (VPCs). METHOD: In academic years 2013-2014 and 2014-2015, cohorts of students in
      pediatrics (Peds), family medicine (FM), and internal medicine (IM) clerkships
      were allocated to either core required use (CRU) or self-directed use (SU) of
      MedU VPCs. Outcomes included number and time of case review, student perception
      of learning from VPCs, National Board of Medical Examiners (NBME) subject
      examination scores, and summative clinical ratings for medical knowledge and
      differential diagnoses/problem solving. Focus groups were conducted each year.
      Mean differences were compared by t test. RESULTS: A total of 255 students
      participated in the study. Mean number of cases completed by the CRU group was
      significantly higher than that by the SU group (13.9 vs. 3.1 for FM, 16.1 vs. 3.9
      for Peds, and 10.4 vs. 1.2 for IM) (P < .001). Student-perceived value ratings of
      VPCs were similar between groups. Students described VPCs as time consuming but
      useful for supplementing clinical conditions not seen in person. Mean scores on
      NBME subject examinations for CRU versus SU groups were not different between
      groups in any clerkship, nor were there significant differences in the summative
      clinical ratings for medical knowledge or differential diagnosis/clinical
      reasoning. CONCLUSIONS: Although VPCs continue to serve an important role in
      exposing students to clinical conditions not seen in person, the optimal
      employment of this technology in clerkship pedagogy requires further exploration.

PMID- 29045277
TI  - Determinants of Improvement in Cardiopulmonary Exercise Testing After Left
      Ventricular Assist Device Implantation.
AB  - Although improvement in cardiac output and hemodynamic parameters is routinely
      demonstrated in patients implanted with continuous-flow left ventricular assist
      devices (CF-LVADs), improvement in exercise capacity is inconsistently seen. Our
      purpose was to determine whether native cardiac factors, LVAD factors, or
      comorbid factors were associated with lack of improvement. Review of all patients
      undergoing preimplant cardiopulmonary exercise testing (CPET) and CPET on LVAD
      therapy at one institution was performed between 2007 and 2014 (n = 49).
      Comprehensive assessment of echocardiographic parameters, right heart
      catheterization data, medications, and comorbid illness was undertaken. There was
      no mean improvement in peak oxygen consumption (VO2; 11.8-12.4 ml/kg/min; p =
      0.26), although exercise time (5.1 [46% predicted] to 5.8 min [56% predicted]; p
      = 0.02) and nadir of the ratio of minute ventilation to carbon dioxide production
      slope (VE/VCO2; 39-36; p = 0.001) improved. Factors most strongly associated with
      improvement in VO2 were Heartmate II pulsatility index (PI; R = 0.48; p = 0.001),
      power (R = -0.40; p = 0.009), pump flow (R = -0.40; p = 0.008), and pump speed (R
      = -0.32; p = 0.04). Peak heart rate (HR) was also associated with improvement in
      VO2 (R = 0.41; p = 0.004). Left ventricular ejection fraction (LVEF; R = 0.004; p
      = 0.77), right ventricular (RV) function (R = 0.22; p = 0.28), and aortic valve
      opening (R = 0.20; p = 0.57) were not associated with improvement in VO2. Our
      data suggest that less reliance on LVAD support was modestly associated with
      improvement in exercise capacity. Further studies should seek to determine the
      optimal level of device support prospectively in relation to exercise capacity.

PMID- 29045278
TI  - Angulated Stents-A Novel Stent Improvisation to Manage Difficult Post
      tuberculosis Bronchial Stenosis.
AB  - Post-tuberculosis bronchostenosis (PTBS), a complication of endobronchial
      tuberculosis is currently treated by bronchial stenting. However, in cases of
      angulated bronchial stenoses, difficulty is often encountered in stent insertion
      and maintenance, resulting in stent migration, granulation tissue overgrowth, and
      restenosis. To accommodate the angulated alignment of the stenosis, we devised an
      "angulated stent"-a novel improvisation of the conventional stent via splicing
      and suturing to achieve a resultant angulated shape. A retrospective review was
      undertaken to evaluate the performance of this stent. Among 283 PTBS patients who
      underwent interventional bronchoscopy at our center from 2004 to 2014, 21 were
      treated with at least one angulated stent. Clinical outcomes, including the
      stenting duration were investigated. After a median follow-up of 26 months, stent
      removal was successful in 7 (33.3%) out of 21 patients. In patients managed with
      angulated stents, the median duration to stent change or eventual removal was
      longer than those treated with straight tube stents (392 days vs. 86 days; p <
      0.05). Angulated stents are a feasible treatment option in patients with
      angulated PTBS by reducing complications and prolonging the stent-changing
      interval.

PMID- 29045279
TI  - Leaflet Kinematics of Mechanical and Bioprosthetic Aortic Valve Prostheses.
AB  - The hemodynamic performance of artificial aortic valves (AVs) and the probability
      for structural valve deterioration can be linked to the valve kinematics.
      Comparability among different studies is limited because of variations in the
      experimental setups and physiologic boundary conditions. This study presents
      results of kinematic measurements of bioprosthetic and mechanical AVs that were
      tested in an identical experimental setting such that they can be directly
      compared with each other. The kinematics of AVs is typically presented in the
      form of the geometric orifice area and its temporal evolution. These parameters
      cannot capture asynchronous leaflet motion and out-of-plane leaflet velocity. In
      this work, each leaflet was tracked individually for a more detailed
      understanding of the leaflet kinematics, asynchronous leaflet motion, and leaflet
      tip velocities. A bioprosthetic valve, Edwards INTUITY (EINT), and two mechanical
      valves, Medtronic ADVANTAGE (MADV) and a Lapeyre-Triflo FURTIVA (TFUR), were
      tested in a compliant model of the aortic root in a physiologic flow loop. TFUR
      and MADV opened alike with maximum leaflet tip velocities of 0.77 and 0.66 m/s,
      respectively. The opening of EINT showed significantly higher local in-plane
      leaflet velocities of more than 2 m/s. EINT and TFUR exhibited similar early and
      slow closure. MADV closed significantly later with increased velocity. TFUR had a
      median maximum leaflet tip velocity of 0.39 m/s during valve closure and that of
      MADV was 0.83 m/s, whereas EINT exhibited a median maximum local in-plane leaflet
      velocity of 0.37 m/s. EINT experienced leaflet fluttering during systole with a
      flapping frequency of 36 Hz.

PMID- 29045280
TI  - Sedation Practice in Extracorporeal Membrane Oxygenation-Treated Patients with
      Acute Respiratory Distress Syndrome: A Retrospective Study.
AB  - Our objective was to characterize sedation management in adult patients with
      severe respiratory distress syndrome (ARDS) treated with venovenous
      extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective chart
      review of these patients treated at Toronto General Hospital between January 2012
      and October 2015. Medications administered (sedative, analgesic, paralytic, and
      antipsychotic), sedation depth (Sedation Agitation Scale [SAS] score) delirium
      assessments, and mobilization were recorded daily. Forty-five adults (33 males,
      median age 47 years; interquartile range [IQR], 35-56]) with ARDS (median
      PaO2/FiO2 71; IQR 59-83) because of respiratory infection (91%) were treated with
      VV-ECMO for a median of 11 days (IQR, 7-17). After ECMO initiation, 96% patients
      were deeply sedated (SAS score < 3) with continuous infusions of midazolam (49%),
      propofol (18%), or both (29%) and 98% were receiving opioid infusions (93%
      fentanyl). Patients were deeply sedated for a median of 6 days (IQR, 3-10) after
      cannulation before transitioning to intermediate or light sedation (SAS score >=
      3). Before ECMO discontinuation, 77% of surviving patients were intermediately or
      lightly sedated, 20% were receiving no sedatives, and 9% were receiving no
      opioids. During ECMO, 58% had positive delirium assessment and 24% experienced
      agitation (SAS >= 6). During ECMO support, 71% received physical therapy that
      occurred after a median of 7 days (IQR, 4-12) after cannulation. In conclusion,
      we found that although patients were deeply sedated for a prolonged duration
      after VV-ECMO initiation, many were able to safely achieve light sedation and
      active mobilization.

PMID- 29045281
TI  - Pharmacokinetics of Amikacin in Critical Care Patients on Extracorporeal Device.
AB  - In this study, we evaluate the effect of extracorporeal membrane oxygenation
      (ECMO) and ventricular assist devices (Levitronix) on the pharmacokinetic of
      amikacin in critically ill patients. Twelve patients with ECMO and three with
      Levitronix devices who started treatment with amikacin were included. Amikacin
      pre (Cmax) and post (Cmin) dose serum concentrations were measured during the
      first 72-96 hours of treatment initiation. Pharmacokinetic parameters were
      performed by Bayesian adjustment. The median initial dose was 1,000 mg (range:
      600-1,400 mg). Mean plasma concentrations were Cmax 58.6 mg/L (17.0 mg/L); Cmin
      9.58 mg/L (7.8 mg/L). Patients with an ECMO device had a higher volume of
      distribution (0.346 [0.033] vs. 0.288 [0.110] L/kg) and a lower plasma clearance
      (1.58 [0.21] vs. 3.73 [1.03] L/h) than the control group. This phenomenon was
      also observed in those patients with simultaneous use of ECMO and
      hemodilafiltration. For patients with Levitronix system, no significant
      alterations in the volume of distribution were observed, although a lower plasma
      clearance was noticed. Placement of ECMO devices alters the pharmacokinetic
      parameters of amikacin in the critically ill patients and should be considered
      when selecting the initial dose.

PMID- 29045282
TI  - Prediction Model for Wait Times in Cardiac Transplantation.
AB  - Wait times have increased for patients approved for heart transplants. We
      reviewed United Network for Organ Sharing (UNOS) data for 14,242 patients listed
      for isolated heart transplant (2009-2013) to develop a risk score model for
      timing left ventricular assist device (LVAD) implantation in bridge-to-transplant
      patients. We used a multivariable Cox proportional hazards regression model with
      subsequent bootstrap resampling for internal validation to develop a scoring
      system that combined risk factors, weighted by the corresponding regression
      coefficients, to define an individual's risk score. Four risk factors were
      identified (body mass index, blood type, region, and urgency status) to be
      significantly and independently associated with wait time (p < 0.001), showing
      adequate model discrimination (C = 0.704) and calibration. Higher risk scores
      correlated with shorter wait times. Our model corresponded closely with observed
      transplant rates, predicting longer wait times for lower status, larger size,
      certain blood groups, and some UNOS regions. This tool has the potential to more
      accurately describe the wait-time duration for an individual patient, which may
      influence care decisions. The wait-time discrepancies (blood types/regions)
      reinforce the need to reevaluate the geographic-allocation policy. The proposed
      review of the UNOS heart allocation policy may make this model especially
      relevant.

PMID- 29045283
TI  - Timing of Initiation of Antiretroviral Therapy and Risk of Preterm Birth in
      Studies of HIV-infected Pregnant Women: The Role of Selection Bias.
AB  - BACKGROUND: Women who initiate antiretroviral therapy (ART) during pregnancy are
      reported to have lower risk of preterm birth compared with those who enter
      pregnancy care already receiving ART. We hypothesize this association can be
      largely attributed to selection bias. METHODS: We simulated a cohort of 1000
      preconceptional, HIV-infected women, where half were randomly allocated to
      receive immediate ART and half to delay ART until their presentation for
      pregnancy care. Gestational age at delivery was drawn from population data
      unrelated to randomization group (i.e., the true effect of delayed ART was null).
      Outcomes of interest were preterm birth (<37 weeks), very preterm birth (<32
      weeks), and extreme preterm birth (<28 weeks). We analyzed outcomes in 2 ways:
      (1) a prospectively enrolled clinical trial, where all women were considered (the
      intent-to-treat (ITT) analysis); and (2) an observational study, where women who
      deliver before initiating ART were excluded (the naive analysis). We explored the
      impact of later ART initiation and gestational age measurement error on our
      findings. RESULTS: Preconception ART initiation was not associated with preterm
      birth in ITT analyses. Risk ratios (RRs) for the effect of preconception ART
      initiation were RR = 1.10 (preterm), RR = 1.41 (very preterm), and RR = 5.01
      (extreme preterm) in naive analyses. Selection bias increased in the naive
      analysis with advancing gestational age at ART initiation and with introduction
      of gestational age measurement error. CONCLUSIONS: Analyses of preterm birth that
      compare a preconception exposure to one that occurs in pregnancy are at risk of
      selection bias. See video abstract at, http://links.lww.com/EDE/B313.

PMID- 29045284
TI  - Increasing Colorectal Cancer Screening Using a Quality Improvement Approach in a
      Nurse-Managed Primary Care Clinic.
AB  - According to the American Cancer Society, 1 in 23 Americans will be diagnosed
      with colorectal cancer (CRC) in their lifetime. Screening for CRC is an
      effective, yet underused preventive approach. This is especially true in rural
      areas, where only 35% of patients were found to be up to date on their screenings
      in 2014. Increasing CRC screening can produce positive patient outcomes by early
      recognition and removal of precancerous polyps. The purpose of this project was
      to use quality improvement (QI) interventions to increase CRC screening rates at
      a nurse-managed clinic in rural Indiana. Using Deming's Plan-Do-Study-Act QI
      model, multiple interventions were implemented which resulted in a 37% increase
      in the number of screenings ordered on eligible patients and an overall increase
      of 28% in the completion of the screenings. This project contributes to
      healthcare quality knowledge by also suggesting that the fundamental principles
      of encouraging staff feedback to gain buy-in, improving processes informed by
      patient data, and valuing frequent performance feedback to staff, strengthened
      this QI project and ensured adoption and sustainability of these results.

PMID- 29045285
TI  - Milrinone Dosing and a Culture of Caution in Clinical Practice.
AB  - Milrinone is an invaluable agent in the treatment of end-stage heart failure
      patients who are refractory to optimal medical therapy. In addition to its use in
      acute decompensated heart failure, milrinone can also be employed as a home
      infusion therapy or a bridge to cardiac transplant. Concerns about its adverse
      effects, such as an increased risk of arrhythmias and hypotension, often limit
      the doses of milrinone used in clinical practice. In addition, milrinone is
      infrequently used or avoided entirely in patients with acute renal failure or end
      stage renal disease because the drug is primarily cleared by renal excretion.
      Despite these concerns, studies that comprehensively reconcile the dose-response
      relationship and adverse events are scarce, and no clear provisions exist to
      guide milrinone dosing. After a brief discussion of the pharmacokinetics of
      milrinone, this article examines milrinone dosing, observed hemodynamic benefits,
      and documented adverse events across different studies.

PMID- 29045286
TI  - Ability of Nonstrain Diastolic Parameters to Predict Doxorubicin-Induced
      Cardiomyopathy: A Systematic Review With Meta-Analysis.
AB  - Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy. Prior
      studies have found conflicting results of whether nonstrain diastolic parameters
      can predict doxorubicin-induced cardiotoxicity. We performed a systematic review
      of English written publications using Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guidelines. The following inclusion criteria
      were applied: cancer subjects, echo-derived nonstrain diastolic profile, and
      patients compared before and after treatment to predict systolic dysfunction. The
      following exclusion criteria were applied: other cardiotoxic agents, non-echo
      studies, or used protective medications. Meta-analysis was performed using
      comprehensive meta-analysis software V3 to calculate cumulative means, SD, and
      odds ratios (ORs). Only 4 studies were designed to predict doxorubicin-induced
      cardiotoxicity. Of the 7 common parameters identified among studies, only 4 were
      significant: mitral E [OR: 3.4; 95% confidence interval (CI): 1.5-7.8; P =
      0.003]; lateral E' (OR: 3.7; 95% CI: 1.5-9.4; P < 0.005); mitral E/A (OR: 4.3;
      95% CI: 2.1-8.9; P < 0.0001); and lateral S' (OR: 2.7; 95% CI: 1.2-5.8; P =
      0.01). We found that conventional nonstrain diastolic parameters predicted
      doxorubicin-induced systolic dysfunction. Whether nonstrain diastolic parameters
      can be used to supplement strain imaging for predicting doxorubicin-induced
      systolic function warrants further investigation in larger studies.

PMID- 29045287
TI  - Yosprala: A Fixed Dose Combination of Aspirin and Omeprazole.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in the
      United States. Patients who survive a primary cerebrovascular or cardiovascular
      event are at increased risk of a subsequent occurrence. Antiplatelet therapy
      plays an essential role for secondary prevention in individuals with stroke,
      transient ischemic attack, acute or chronic artery disease, or peripheral
      arterial disease. Maintaining high-risk patients on low-dose aspirin therapy is a
      fundamental component of management. However, poor adherence, secondary to the
      drug's gastrointestinal side effects, has been associated with negative
      cardiovascular outcomes. Numerous studies have indicated that proton-pump
      inhibitors significantly reduce the risk of upper gastrointestinal adverse events
      in aspirin-treated patients. The US Food and Drug Administration approved
      Yosprala (Aralez Pharmaceuticals), a fixed-dose combination of delayed-release
      aspirin and immediate-release omeprazole, on September 15, 2016. It is the first
      product to become available in the United States that combines these 2
      pharmacologic drug classes, and represents a new therapeutic option for patients
      and healthcare providers who strive to improve adherence to daily aspirin
      therapy.

PMID- 29045288
TI  - Effects of Anti-Inflammatory Medications in Patients With Coronary Artery
      Disease: A Focus on Losmapimod.
AB  - Inflammation plays an integral role in atherogenesis and the pathogenesis of
      coronary artery disease (CAD). The question remains as to whether targeted
      inhibition of specific pathways of inflammation will have any clinical benefits
      in CAD. In this article, we will review p38 mitogen-activated protein kinase, one
      of the key sensors of cellular stress that plays an important role in the
      inflammatory cascade. In addition, we will review losmapimod, a reversible
      competitive inhibitor of the alpha and beta isoforms of p38 mitogen-activated
      protein kinase, and its efficacy when added to standard of care in patients
      hospitalized with myocardial infarction. In the phase III trial, LATITUDE-TIMI
      60, the investigators found that treating patients hospitalized with acute
      myocardial infarction with losmapimod did not reduce the risk of major adverse
      cardiovascular events. Lastly, we will briefly review trials recently completed
      and currently underway, investigating other anti-inflammatory medications such as
      canakinumab, methotrexate, varespladib, darapladib, and colchicine, and their
      role in CAD.

PMID- 29045289
TI  - Genetic Origins of Tetralogy of Fallot.
AB  - Due to improved survival and clinical outcomes, congenital heart disease (CHD) is
      an area of growing importance within the medical community. As these patients
      reach adulthood and have children, there has been a growing appreciation for the
      increased risk of CHD among their offspring, strongly implying a genetic element.
      Given the growing wealth of genetic data available and these clinical
      implications, this review serves to reexamine the role of genetics within CHD,
      using Tetralogy of Fallot as a model pathology. Tetralogy of Fallot (TOF) is one
      of the oldest documented CHDs, with a growing prevalence of adult patients, and
      thus serves as an excellent model for this review. Given the complex nature of
      cardiac development, it is not surprising that multiple transcription factors and
      signaling molecules responsible for cardiogenesis have been implicated in TOF,
      with additional, previously nonimplicated genes being routinely reported within
      the literature. This review focuses on the well-characterized genes gata4,
      nkx2.5, jag1, foxc2, tbx5, and tbx1, which have been previously implicated in
      TOF. Furthermore, this article will attempt to summarize the specific clinical
      implications associated with the affected genes, such as right-sided aortic
      arches, associated syndromic presentations, and parental carrier states.

PMID- 29045290
TI  - The Prognostic Implications of Two-Dimensional Speckle Tracking Echocardiography
      in Hypertrophic Cardiomyopathy: Current and Future Perspectives.
AB  - Two-dimensional speckle tracking echocardiography represents a novel, simple, and
      reproducible technique for the estimation of left ventricular myocardial
      deformation (strain) and the evaluation of left ventricular twist mechanics.
      During the last few years, its clinical and prognostic implications in
      cardiomyopathies and hypertrophic cardiomyopathy (HCM), in particular, have been
      rapidly increasing. Reduced global longitudinal strain is associated with more
      severe disease and confers an increased risk for major cardiac events,
      independently of other clinical and echocardiographic risk factors. Left
      ventricular dyssynchrony also seems promising as a risk factor for sudden cardiac
      events. With respect to left atrial mechanics, left atrial reservoir, conduit,
      and contractile strain may also confer an increased prognostic value for atrial
      fibrillation, major cardiac events, and even sudden death. Although right
      ventricular global longitudinal strain is impaired in HCM compared with healthy
      controls and individuals with physiological hypertrophy, its prognostic
      significance is currently unknown. Conclusively, 2-dimensional speckle tracking
      imaging seems promising for HCM. However, future studies are needed to
      incorporate this new imaging technique in the standard evaluation of an HCM
      individual.

PMID- 29045291
TI  - Devices for Autonomic Regulation Therapy in Heart Failure With Reduced Ejection
      Fraction.
AB  - Heart failure (HF) is associated with significant morbidity and mortality and an
      increasing economic burden. The persistence of HF's risk factors, coupled with an
      aging population, also leads to an increase in its incidence and prevalence. It
      is well established that sympathetic hyperactivity and parasympathetic withdrawal
      are instrumental in the development and worsening of HF. Therefore, restoring
      autonomic balance to the cardiovascular system is an attractive therapeutic
      approach. The following is a review of current clinical trials of device-based
      autonomic regulation therapy in the management of HF with a reduced ejection
      fraction.

PMID- 29045292
TI  - Ovarian Metastases of Breast Cancers With Signet Ring Cells: A Report of 17 Cases
      Including 14 Krukenberg Tumors.
AB  - Krukenberg tumor, defined as metastatic adenocarcinoma to the ovary containing at
      least 10% signet ring cells, usually arises from the stomach but can also
      originate from other sites. We reviewed 17 metastatic breast carcinomas to the
      ovary with signet ring cells to potentially identify features indicative of
      mammary origin as opposed to other possible primary sites. The patients ranged
      from 41 to 76 (mean, 53.6) yr. Fourteen had a prior history of invasive breast
      carcinoma (invasive ductal carcinoma, 4; invasive lobular carcinoma, 3;
      adenocarcinoma not otherwise specified, 3; carcinoma with ductal and lobular
      features, 2; and unspecified carcinoma, 2) and metastases were identified 2 to
      284 (mean, 79) mo after the original diagnosis. Three patients had no known
      history of invasive breast carcinoma: 1 was subsequently diagnosed with invasive
      lobular carcinoma, 1 had suspicious bilateral breast masses identified on
      imaging, and 1 was lost to follow-up. Bilateral ovarian metastases were present
      in 87%, and the tumors ranged from 3.8 to 19 (mean, 8) cm. Microscopically the
      ovarian architecture was effaced in 71% by discrete tumor lobules separated by
      striking edema. The tumors exhibited a variety of histologic patterns: nests were
      most common (88%), followed by cords (82%), diffuse sheets (82%), single cells
      (71%), small clusters (41%), glands (29%), and follicle-like cysts (12%). Signet
      ring cells comprised 2% to 70% (mean, 33%) of the tumors, with 14 cases meeting
      the criteria for Krukenberg tumor. Signet ring cells were most frequently
      observed within diffuse sheets (71%) and cords (65%). Tumor cells arranged in
      nests, cords, and diffuse sheets are typical of Krukenberg tumor of breast
      origin, and the patterns recapitulate those seen in primary breast carcinomas.
      Features characteristic of gastrointestinal origin, such as extracellular mucin,
      intestinal-type glands, dirty necrosis, microcysts, and goblet cell carcinoid
      like foci, were absent. The overall morphologic picture in cases of ovarian
      spread of breast cancer with signet ring cells is usually strongly suggestive of
      mammary origin. The diagnosis can be further supported by the clinical history
      and immunohistochemical evaluation.

PMID- 29045293
TI  - The road to precision medicine in asthma: challenges and opportunities.

PMID- 29045295
TI  - Foreword.

PMID- 29045296
TI  - Taking the Tube: From Normal Fallopian Tube Epithelium to Ovarian High-grade
      Serous Carcinoma.
AB  - Detailed pathologic studies over the past decade suggest a distal fallopian tube
      origin for the majority of "ovarian" high-grade serous carcinomas (HGSC). This
      review will summarize molecular alterations observed in tubal precursors for
      HGSC, namely p53 signatures and serous tubal intraepithelial carcinomas, and in
      nonmalignant fallopian tube epithelial cells obtained from women at increased
      genetic risk for HGSC. Recent experiments investigating the impact of follicular
      fluid exposure and retrograde menstruation on tumor development in the fallopian
      tube will also be discussed. These data will be reconciled with traditional
      ovarian cancer risk factors related to reproductive history.

PMID- 29045299
TI  - The Future of Cesarean Delivery Rates in the United States.
AB  - The US cesarean delivery rate remains 30%-32%. Increases in maternal age,
      obesity, and diabetes put upward pressure on this rate. Alternatives to cesarean
      delivery, vaginal birth after cesarean (VBAC), and operative vaginal delivery,
      are underutilized and there are substantial challenges to their resurgence.
      Practice guidelines offer promise, but demonstrate only minor reductions in
      cesarean delivery. We estimate that the overall rate in the US will remain 27%
      30% for the immediate future. As more states move to recognize the independent
      practice of midwifery and more payers seek lower cost options for childbirth, we
      anticipate the overall rate will drop to 20% or 25%, but not for another 15 years
      or more.

PMID- 29045301
TI  - Cannabinoid Hyperemesis Syndrome (CHS): A Parisian Case Series.

PMID- 29045302
TI  - Neurosteroid Levels in Patients With Bipolar Disorder and a History of Cannabis
      Use Disorders.
AB  - PURPOSE/BACKGROUND: In animal models, levels of the neurosteroid pregnenolone
      increase after tetrahydrocannabinol (THC) administration and pregnenolone appears
      to attenuate the brain effects of THC. Given these interactions between
      pregnenolone and THC, we evaluated baseline neurosteroid levels in participants
      with a history of a cannabis use disorders (CUDs). METHODS/PROCEDURES: Bipolar
      depressed participants were enrolled in a randomized placebo-controlled clinical
      trial to evaluate the efficacy of add-on pregnenolone for depression and before
      receiving pregnenolone or placebo. Baseline serum levels of neurosteroids
      (pregnenolone, allopregnanolone, pregnanolone, and androsterone) were analyzed in
      53 participants with highly sensitive and specific gas chromatography/mass
      spectrometry. Current, active substance use disorders, or a positive baseline
      urine drug screen, were exclusionary. Participants were classified by past
      cannabis abuse or dependence diagnosis using the structured clinical interview
      for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Data
      were analyzed by independent t tests for separate neurosteroids.
      FINDINGS/RESULTS: Participants with a history of CUD had higher serum
      pregnanolone, lower allopregnanolone, a higher pregnanolone to allopregnanolone
      ratio, and a lower pregnenolone to pregnanolone ratio compared with those without
      a history of cannabis use. Similar findings were not observed based on a history
      of other substance use disorders with the exception of lower allopregnanolone in
      those with opioid use disorders. Notably, the majority of those with an opioid
      use disorder also had a CUD (75%). IMPLICATIONS/CONCLUSIONS: These findings
      potentially suggest either enduring changes in neurosteroids in people with past
      CUDs or represent a vulnerability marker for a CUD.

PMID- 29045303
TI  - Riluzole Serum Concentration in Pediatric Patients Treated for Obsessive
      Compulsive Disorder.
AB  - PURPOSE/BACKGROUND: The goals of this study were to determine whether pediatric
      serum concentration of riluzole is similar to that observed in adults and to
      determine whether riluzole serum concentration is associated with adverse effects
      or efficacy in children and adolescents with treatment-refractory obsessive
      compulsive disorder. METHODS/PROCEDURES: Data were drawn from previously
      published studies: 1 open-label trial and 1 randomized controlled trial with an
      open-label extension phase. Serum was drawn at 24, 36, and 52 weeks in 37
      patients who were taking approximately 100 mg riluzole daily (mean dose at 24
      weeks, 99 +/- 28 mg). FINDINGS/RESULTS: Across all samples, serum riluzole
      concentration ranged from 7 to 963 ng/mL. At week 24 (n = 37), the median
      concentration was 76 ng/mL (interquartile range, 53-172 ng/mL). Within-patient
      concentration was relatively stable. One subject who had the highest serum
      concentration levels during the study developed pancreatitis after exiting the
      study. The patient had recently added fluvoxamine to the riluzole regimen.
      Controlling for concomitant fluvoxamine (in 6 participants) and time of draw,
      serum riluzole concentration was not associated with obsessive-compulsive
      disorder symptom severity, nor was it associated with adverse effect profile.
      IMPLICATIONS/CONCLUSIONS: The dose of riluzole used in these pediatric subjects
      seems to have achieved serum concentration levels similar to those observed in
      adults. However, as previously reported in adults, the serum concentration had no
      discernable relationship to efficacy or adverse effects.

PMID- 29045304
TI  - Effect of Clozapine vs Other Second-Generation Antipsychotics on Hospitalization
      and Seclusion: A Retrospective Mirror-Image Study in a Japanese Public
      Psychiatric Hospital.
AB  - BACKGROUND: Clozapine has been regarded as the gold standard for patients with
      treatment-resistant schizophrenia, but a recent network meta-analysis has
      questioned its relative superiority over other second-generation antipsychotics
      (SGAs) such as olanzapine and risperidone. PURPOSE: We conducted a retrospective
      mirror-image study of clozapine vs other SGAs to evaluate real-world
      effectiveness of clozapine in terms of the duration of hospitalization and
      seclusion, both of which represent a critical outcome. METHODS: We included all
      patients who initiated clozapine at the Yamanashi Prefectural KITA Hospital and
      had continued to take any SGA(s) other than clozapine for at least 1 year before
      the initiation of clozapine. We obtained data on hospitalization and seclusion
      during 1 year of SGA treatment (SGA phase) and 1 year after the treatment was
      switched to clozapine (clozapine phase). RESULTS: The study included 35 patients
      (21 men, 31 with schizophrenia, 4 with schizoaffective disorder) with the average
      +/- SD age of 37.3 +/- 11.1 years. The results indicated that total
      hospitalization days did not differ significantly between SGA and clozapine
      treatment. However, total duration of seclusion was significantly shorter in the
      clozapine phase than in the SGA phase. Furthermore, the number of patients who
      were secluded at least once was significantly smaller in the clozapine phase than
      in the SGA phase. The results were essentially unchanged when outlier patients
      were excluded and only when patients taking olanzapine and/or risperidone during
      the SGA phase were considered. CONCLUSIONS: Although the findings from this
      retrospective analysis need to be further tested in prospective trials, they
      endorse the relative effectiveness of clozapine over other SGAs in the real
      world.

PMID- 29045305
TI  - Hypothermia Associated With Antipsychotic Medication: A Clinical Surveillance
      Study.

PMID- 29045306
TI  - Antidepressant Trials: Are the Diminishing Effect Sizes of Efficacy Trials
      Avoidable?

PMID- 29045307
TI  - Prevalence of Antipsychotic-Treated Patients in a Cohort of Adult Addicted
      Patients.
AB  - PURPOSE: The objective of this cross-sectional study was to describe and estimate
      the prevalence of antipsychotics (AP) in a cohort of addicted patients, and to
      compare the profiles of addictive patients receiving AP or not. METHODS: We
      included all adult patients seen at the addiction care center of Montpellier
      University Hospital, between January 1, 2015, and March 31, 2015. Demographic,
      clinical, and therapeutic data were collected from the patients' medical records.
      RESULTS: During the study period, 415 patients were included, with a mean age of
      38 +/- 10 years. They were mostly men (73.3%), French (54.9%), and unemployed
      (61.8%). Among the study population, 93 patients (patients treated with AP
      [trAP], 22.4%) were treated by 111 different AP, mainly cyamemazine (29.0% of
      treated patients), aripiprazole (20.4%), olanzapine (17.2%), and quetiapine
      (16.1%), mostly in monotherapy (80.6%) and by oral route (93.2% of AP).
      Psychiatric history was more frequent in trAP than in those without AP (untrAP)
      (55.9% vs 35.4% respectively; P < 0.001). Professional activity tended to be less
      frequent in patients with AP (25.3% vs 38.9%, P = 0.08).When compared with
      untrAP, trAP consumed more amphetamine (10.8% vs 4.4%; P = 0.02) and tended to
      consume less opiates (7.5% vs 14.9%; P = 0.06); the consumptions of cannabis
      (43.0% vs 35.7%; P = 0.20) and cocaine (22.6% vs 16.8%; P = 0.20) were not
      statistically different.Opiate maintenance therapy was reported in 63.7% of trAP
      and 68.4% of untrAP (P = 0.41): it consisted of methadone (trAP, 60.3% vs untrAP,
      56.5%) and buprenorphine (trAP, 39.7% vs untrAP, 43.5%). CONCLUSIONS: The
      concomitant management of psychiatric and substance use disorders in the same
      center may explain the high prevalence of trAP in this study. Cannabis and
      psychostimulants may have been used in these patients as self-medication for
      mental disease-related symptoms or adverse effects of APs.

PMID- 29045308
TI  - Thirty days only double antiplatelet therapy after drug-eluting stenting: could a
      'short-term' treatment be advantageous?

PMID- 29045309
TI  - Cardiovascular mortality among 76 864 survivors of childhood cancers in the
      United States: a report from the surveillance, epidemiology, and end-results
      program.

PMID- 29045310
TI  - Risk of stroke after transcatheter prosthetic aortic valve implant with aortic
      bioprosthesis: subclinical thrombosis and possible therapeutic implications.

PMID- 29045311
TI  - Cardiac resynchronization therapy outcomes in patients with chronic heart
      failure: cardiac resynchronization therapy with pacemaker versus cardiac
      resynchronization therapy with defibrillator.
AB  - AIMS: Cardiac resynchronization therapy (CRT) for chronic heart failure with left
      ventricular systolic dysfunction (LVSD) consistently improves survival against
      optimal medical therapy alone. Limited data exist comparing the outcomes between
      CRT with pacemaker (CRT-P) and with defibrillator (CRT-D). We aimed to
      investigate the long-term prognosis of patients who received CRT-P or CRT-D.
      METHODS AND RESULTS: Data were prospectively collected from consecutive patients
      with standard indications for CRT, who were implanted at a single large tertiary
      centre between 2008 and 2012. All-cause mortality was compared between those
      patients who received either CRT-P or CRT-D. A subgroup analysis was performed in
      patients with ischaemic cardiomyopathy. During the period in question, 795
      patients received CRT devices: 544 (68.4%) CRT-P and 251 (31.6%) CRT-D. The mean
      follow-up was 1072 +/- (SD 556) days. Overall, there was no survival benefit in
      those patients implanted with a CRT-D compared with CRT-P (hazard ratio 1.09, 95%
      confidence interval 0.84-1.41, P = 0.51). In patients with ischaemic chronic
      heart failure [n = 530 (66.7%)], there was a trend for improved survival with CRT
      D; however, this was not significant after adjustment. In a subgroup analysis,
      there were no differences in mode-specific mortality in those patients implanted
      with CRT-D compared with CRT-P. CONCLUSION: In this large consecutive patient
      cohort, we did not find a survival benefit of CRT-D compared with CRT-P. Patients
      indicated for CRT devices may not reliably benefit from the addition of a
      defibrillator.

PMID- 29045312
TI  - Validation of the nonlaboratory-based Framingham cardiovascular disease risk
      assessment algorithm in the Atherosclerosis Risk in Communities dataset.
AB  - BACKGROUND: Nonlaboratory-based (non-LB) algorithms have been developed to
      facilitate absolute cardiovascular risk assessment in resource-constrained
      settings. The non-LB Framingham algorithm, which substitute BMI for lipids in
      laboratory-based Framingham, exhibits best performance among non-LB algorithms.
      However, its external validity has not been evaluated. AIM: To examine the
      validity of non-LB Framingham algorithm in Atherosclerosis Risk in Communities
      dataset, and contrast performance with the laboratory-based Framingham algorithm.
      METHODS: We developed Cox regression models including non-LB and laboratory-based
      Framingham covariates in Atherosclerosis Risk in Communities dataset.
      Discrimination was assessed via C-statistic, calibration via goodness-of-fit, and
      marginal discrimination value of BMI vis-a-vis lipids vis-a-vis waist-hip ratio
      via net reclassification improvement (NRI). Both models were compared via area
      under receiver operating characteristic. RESULTS: Among 11 601 participants (mean
      age 54 years, 55% women, 23% black), non-LB vs. laboratory-based Framingham
      performed as follows: C-statistic 0.75 vs. 0.76 among women and 0.67 vs. 0.68
      among men; goodness-of-fit 14.2 vs. 10.5 among women and 25.8 vs. 21.8 among men.
      Overall area under receiver operating characteristic was 0.706 vs. 0.710,
      respectively, with no racial differences in discrimination or calibration. BMI
      and total cholesterol had no impact on NRI. Incremental predictive value of HDL
      was comparable with waist-hip ratio (category-less NRI = 0.34 vs. 0.31;
      categorical NRI = 0.06 vs. 0.05, P < 0.01). CONCLUSION: These results demonstrate
      the validity and limitations of the non-LB Framingham algorithm in a biracial
      cohort. Substituting BMI with a central adiposity metric such as waist-hip ratio
      or waist circumference could make the algorithm better or at par with the
      laboratory-based Framingham algorithm.

PMID- 29045313
TI  - Importance of Axial Length and Functional Corneal Endothelial Cells in Descemet
      Membrane Endothelial Keratoplasty.

PMID- 29045314
TI  - Repeated-Sprint Ability in Division I Collegiate Male Soccer Players: Positional
      Differences and Relationships with Performance Tests.
AB  - Repeated-sprint ability (RSA) in essential for soccer. Important considerations
      when assessing RSA is whether there are differences between positions (defenders,
      midfielders, forwards), and what physiological characteristics may contribute to
      RSA. This has not been assessed in collegiate male players. Eighteen Division I
      male field players from one school performed several performance tests. The RSA
      test involved 7 x 30-m sprints completed on 20-s cycles. Measurements included
      total time (TT), and performance decrement (percent change in time from the first
      to last sprint; PD). Subjects also completed tests of lower-body power (vertical
      [VJ] and standing broad [SBJ] jump); linear (30-m sprint; 0-5, 0-10, 0-30 m
      intervals) and change-of-direction (505) speed; and soccer-specific endurance (Yo
      Yo Intermittent Recovery Test Level 2; YYIRT2). A one-way ANOVA (p < 0.05)
      determined between-position differences, and effect sizes were calculated.
      Pearson's correlations (p < 0.05) calculated relationships between RSA TT and PD
      with the other tests. There were no significant between-position differences for
      any test. There were large effects for the faster right-leg 505 and greater
      YYIRT2 distance for midfielders compared to defenders and forwards. Nonetheless,
      no between-position differences in RSA TT and PD were documented. There were
      relationships between RSA TT and the VJ (r = -0.59), SBJ (r = -0.61), 0-10 m (r =
      0.64) and 0-30 m (r = 0.83) sprint intervals. There were no significant
      correlations for RSA PD. Male field players from one collegiate soccer team can
      demonstrate similar RSA across different positions. Greater lower-body power and
      sprinting speed could augment RSA.

PMID- 29045315
TI  - A Single Dose Of Oral Atp Supplementation Improves Performance And Physiological
      Response During Lower Body Resistance Exercise In Recreational Resistance Trained
      Males.
AB  - The aim of this study was to investigate the acute effect of ATP supplementation
      on performance and physiological responses during resistance exercise in
      recreationally resistance trained males. Eleven men (age= 27.5+/-5.5 yrs, weight=
      83.4+/-9.8 kg, height= 182+/-0.04 cm) completed two randomized, double-blind
      trials: ATP supplement condition (ATP=400mg) or a placebo condition. Thirty
      minutes after supplement consumption, subjects performed four sets of half-squats
      until momentary muscular failure at 80% of the 1RM with two minutes of recovery
      between sets. The total number of repetitions, blood pressure, heart rate, blood
      lactate, and oxygen consumption were evaluated. The total weight lifted were
      higher for the ATP condition compared to placebo (Placebo= 3995.7+/-1137.8, ATP=
      4967.4+/-1497.9 Kg; p= 0.005). Heart rate was higher at set-4 for ATP compared to
      placebo (p<0.001) and oxygen consumption during exercise was greater for ATP
      (p=0.021). There were no differences between conditions for lactate and blood
      pressure. In summary, a single oral dose of ATP supplementation improved lower
      body resistance training performance and energy expenditure in recreational
      resistance trained males.

PMID- 29045316
TI  - Understanding the relationship between coach and athlete perceptions of training
      intensity in youth sport.
AB  - To alleviate issues arising from the over/under prescription of training load,
      coaches must ensure that desired athlete responses to training are being
      achieved. The present study aimed to assess the level of agreement between the
      coach intended (pre-session) and observed (post-session) rating of perceived
      exertion (RPE), with athlete RPE during different training intensities (easy,
      moderate, hard). Coach intended RPE was taken prior to all field based training
      sessions over an 8 week in-season period. Following training, all coaches and
      athletes, whom were participants in hockey, netball, rugby and soccer were asked
      to provide an RPE measure for the completed session. Sessions were then
      classified based on the coaches intended RPE, with a total of 28, 125 and 66
      easy, moderate and hard training sessions collected respectively. A univariate
      analysis of variance was used to calculate within-participant correlations
      between coach intended/observed RPE and athlete RPE. Moderate correlations were
      found between coach intended and athlete RPE for sessions intended to be moderate
      and hard whilst a small correlation was found for sessions intended to be easy.
      The level of agreement between coach and athlete RPE improved following training
      with coaches altering their RPE to align with those of the athlete. Despite this,
      moderate and small differences between coach observed and athlete RPE persisted
      for sessions intended to be easy and moderate respectively. Coaches should
      therefore incorporate strategies to monitor training load to increase the
      accuracy of training periodisation and reduce potential over/under prescription
      of training.

PMID- 29045317
TI  - The Relationships between Height, Arm Length, and Leg Length on the Mechanics of
      the Conventional and High-Handle Hexagonal Bar Deadlift.
AB  - The study investigated relationships between arm (AL) and leg length (LL) and
      conventional deadlift (CD) and high-handle hexagonal bar deadlift (HHBD)
      mechanics. Twenty-three resistance-trained subjects (14 males, 9 females)
      completed a one-repetition maximum (1RM) CD and HHBD. A linear position
      transducer was used to measure: lift distance and duration; peak and mean power,
      velocity, and force; time to peak power and velocity; and work. Right AL and LL
      were measured, and AL-to-LL ratio (AL:LL) was also calculated. Spearman's
      correlations (rho; p < 0.05) computed relationships between anthropometry and
      deadlift mechanics separately for males and females. For the CD in males, greater
      height, AL, and LL related to a longer lift distance, and greater mean force and
      work (rho = 0.54-0.72). For the HHBD, greater height and LL related to greater
      lift distance and work; a higher AL:LL related to time to peak power and velocity
      occurring sooner in the lift (rho = 0.54-0.77). In females, greater height, AL,
      and LL related to a longer CD lift distance (rho = 0.67-0.92). For the HHBD,
      greater height, AL, and LL related to a longer lift distance and greater mean
      velocity (rho = 0.69-0.96). There was a negative relationship between AL and lift
      time (rho = -0.83), which meant longer arms resulted in a lower HHBD lift time.
      AL may have influenced females more, due to the fixed dimensions of the hexagonal
      bar. Coaches should be cognizant of potential differences in CD and HHBD work
      when performed by individuals of different body size.

PMID- 29045318
TI  - Letter to the Editor: Effect of Povidone Iodine 5% on the Cornea, Vision, and
      Subjective Comfort.

PMID- 29045319
TI  - Authors' Response.

PMID- 29045320
TI  - AUTOLOGOUS LENS CAPSULAR FLAP TRANSPLANTATION COMBINED WITH AUTOLOGOUS BLOOD
      APPLICATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE.
AB  - PURPOSE: To report results of lens capsular flap transplantation (LCFT) and
      autologous whole blood application in refractory macular hole (MH) treatment.
      METHODS: Seven phakic and three aphakic eyes with persistent MH after standard
      surgery with internal limiting membrane peeling were studied. Lens capsule flap
      was acquired from the same eye in eight cases (seven phakic and one aphakic). The
      fellow eye was used in two aphakic eyes without sufficient lens capsule. The
      fellow eye underwent simultaneous phacoemulsification. All eyes underwent
      complete vitrectomy, LCFT into the MH, whole blood application, and 15%
      perfluoropropane (C3F8) tamponade. The patients were instructed to maintain a
      face-down or prone position for two weeks postoperatively. Structural and
      functional changes were evaluated. RESULTS: The mean preoperative MH diameter was
      1,472.78 +/- 736.88 MUm. The MH was completely closed in nine eyes: eight eyes
      receiving same-eye LCFT and one receiving fellow-eye LCFT. In the other fellow
      eye LCFT recipient, the MH was partially closed. Visual acuity improved from 1.84
      +/- 0.49 logarithm of the minimum angle of resolution (median Snellen acuity:
      20/1,750, range: 20/4,000-20/125) preoperatively to 1.34 +/- 0.59 logarithm of
      the minimum angle of resolution (median Snellen acuity: 20/450, range: 20/4,000
      20/63) postoperatively (P = 0.009). CONCLUSION: Lens capsular flap
      transplantation and autologous whole blood application may improve anatomical and
      visual outcomes in refractory MH cases. The lens equator and fellow eye may be
      promising sources of LCF.

PMID- 29045321
TI  - FUNDUS-WIDE SUBRETINAL AND PIGMENT EPITHELIAL ABNORMALITIES IN MACULAR
      TELANGIECTASIA TYPE 2.
AB  - PURPOSE: Macular telangiectasia Type 2 (MacTel) causes glial and photoreceptor
      cell death in a small, oval patch in the central retina. Beyond this oval area,
      no disease manifestations have been described so far. Here, we describe a novel
      pathological aspect of MacTel in the retinal pigment epithelium (RPE) that is not
      restricted to the clinically affected area but covers the entire retina. METHODS:
      We have studied postmortem eyes from four patients with MacTel by
      immunohistochemistry and electron microscopy. RESULTS: We found cellular debris
      in the subretinal space (between photoreceptor outer segments and RPE),
      consisting mainly of outer segments and RPE components. In healthy eyes, the RPE
      normally phagocytoses the tips of the continuously growing outer segments, a
      process considered to be essential for photoreceptor survival. However, in the
      patients with MacTel, we found no evidence of ongoing outer segment phagocytosis,
      and the apical surface of the RPE appeared abnormal throughout most of the
      retina. CONCLUSION: Reduced outer segment phagocytosis may explain the
      accumulating debris in the subretinal space but is a surprising finding because
      visual function in the peripheral retina is normal in patients with MacTel.
      Nevertheless, the subclinical pathology might induce a specific stress to which
      the central area is uniquely susceptible.

PMID- 29045322
TI  - Longitudinal Associations between Physical Activity and Educational Outcomes.
AB  - PURPOSE: This longitudinal study examined the role of leisure-time physical
      activity in academic achievement at the end of compulsory basic education and
      educational attainment in adulthood. METHODS: The data were drawn from the
      ongoing longitudinal Cardiovascular Risk in Young Finns Study, which was combined
      with register-based data from Statistics Finland. The study consisted of children
      who were 12 yr (n = 1723, 49% boys) and 15 yr (n = 2445, 48% boys) of age at the
      time when physical activity was measured. The children were followed up until
      2010, when their mean age was 40 yr. Physical activity was self-reported and
      included several measurements: overall leisure-time physical activity outside
      school hours, participation in sports club training sessions, and participation
      in sports competitions. Individuals' educational outcomes were measured with the
      self-reported grade point average at age 15 yr and register-based information on
      the years of completed postcompulsory education in adulthood. Ordinary least
      squares models and the instrumental variable approach were used to analyze the
      relationship between physical activity and educational outcomes. RESULTS:
      Physical activity in adolescence was positively associated with educational
      outcomes. Both the physical activity level at age 15 yr and an increase in the
      physical activity level between the ages of 12 and 15 yr were positively related
      to the grade point average at age 15 yr and the years of postcompulsory education
      in adulthood. The results were robust to the inclusion of several individual and
      family background factors, including health endowments, family income, and
      parents' education. CONCLUSION: The results provide evidence that physical
      activity in adolescence may not only predict academic success during compulsory
      basic education but also boost educational outcomes later in life.

PMID- 29045324
TI  - A Ball Skills Intervention in Preschoolers: The CHAMP Randomized Controlled
      Trial.
AB  - PURPOSE: Fundamental motor skills (FMS) contribute to positive health
      trajectories. A high level of competence in ball skills (a subset of FMS) is a
      predictor for time spent in moderate- to vigorous-intensity physical activity
      during adolescence. This study examined the effects of a ball skills intervention
      on ball skill competence among preschool-aged boys and girls. METHODS: This is a
      two-armed randomized controlled trial. A total of 124 preschoolers (Mage +/- SD =
      48.14 +/- 6.62 months) were randomly assigned to one of two groups, the
      Children's Health Activity Motor Program (CHAMP; n = 81) or control (n = 43). FMS
      were measured before, after (9 wk), and at retention (18 wk) using the object
      control subscale of the Test of Gross Motor Development, Second Edition. Changes
      in ball skill scores were calculated (pretest-posttest, pretest-retention,
      posttest-retention) and were compared using one-way ANOVAs with post hoc Scheffe
      analysis. RESULTS: Findings support that groups demonstrated significantly
      different rates of change from pretest to posttest (F3,117 = 179.45, P < 0.001),
      pretest to retention (F3,113 = 95.8, P < 0.001), and posttest to retention
      (F3,113 = 189.89, P < 0.001). Compared with their control group peers, CHAMP boys
      and girls had greater positive rates of change from pretest to posttest and
      pretest to retention as well as greater negative rates of change from posttest to
      retention. CONCLUSIONS: CHAMP was effective in improving and maintaining ball
      skills in preschool-age boys and girls. Findings support that providing a high
      quality motor skill program in early childhood settings could potentially be a
      sustainable public health approach to promoting FMS and positive developmental
      trajectories for health.

PMID- 29045323
TI  - Effects of a Long-Term Physical Activity Program on Activity Patterns in Older
      Adults.
AB  - PURPOSE: To examine the effect of a long-term structured physical activity (PA)
      intervention on accelerometer-derived metrics of activity pattern changes in
      mobility-impaired older adults. METHODS: Participants were randomized to either a
      PA or health education (HE) program. The PA intervention included a walking
      regimen with strength, flexibility, and balance training. The HE program featured
      health-related discussions and a brief upper body stretching routine.
      Participants (n = 1341) wore a hip-worn accelerometer for >=10 h.d for >=3 d at
      baseline and again at 6, 12, and 24 months postrandomization. Total PA (TPA)
      defined as movements registering 100+ counts per minute-was segmented into the
      following intensities: low-light PA (LLPA; 100-759 counts per minute), high light
      PA (HLPA; 760-1040 counts per minute), low moderate PA (LMPA; 1041-2019 counts
      per minute), and high moderate and greater PA (HMPA; 2020+ counts per minute).
      Patterns of activity were characterized as bouts (defined as the consecutive
      minutes within an intensity). RESULTS: Across groups, TPA decreased an average of
      74 min.wk annually. The PA intervention attenuated this effect (PA = -68 vs HE: 
      112 min.wk, P = 0.002). This attenuation shifted TPA composition by increasing
      time in LLPA (10+ bouts increased 6 min.wk), HLPA (1+, 2+, 5+, and 10+ bouts
      increased 6, 3, 2, and 1 min.wk, respectively), LMPA (1+, 2+, 5+, and 10+ bouts
      increased: 19, 17,16, and 8 min.wk, respectively), and HMPA (1+, 2+, 5+, and 10+
      bouts increased 23, 21, 17, and 14 min.wk, respectively). CONCLUSIONS: The PA
      intervention increased PA by shifting the composition of activity toward higher
      intensity activity in longer-duration bouts. However, a long-term structured PA
      intervention did not completely eliminate overall declines in total daily
      activity experienced by mobility-impaired older adults.

PMID- 29045325
TI  - Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle
      Strength.
AB  - PURPOSE: Calorie restriction (CR) improves health span and delays age-related
      diseases in many species. The multicenter Comprehensive Assessment of Long-term
      Effects of Reducing Intake of Energy (CALERIE) study was the first randomized
      controlled trial of CR in nonobese humans. The aim of this investigation was to
      determine the effects of CR on VO2max and muscle strength in the CALERIE trial.
      METHODS: Healthy, normal-weight, and mildly overweight women and men (n = 218,
      mean +/- SE age = 37.9 +/- 0.5 yr) were randomized to 25% CR or an ad libitum
      (AL) control condition in a 2:1 allocation (143 CR, 75 AL). VO2max was determined
      with an incremental treadmill test; the strength of the knee flexors and
      extensors was assessed by dynamometry at baseline, 1 yr, and 2 yr. RESULTS: The
      CR group achieved an average 11.9% +/- 0.7% CR during the 2-yr intervention. Body
      weight decreased in CR (-7.7 +/- 0.4 kg), but not AL (+0.2 +/- 0.5 kg). Absolute
      VO2max (L.min) decreased at 1 and 2 yr with CR, whereas VO2max expressed relative
      to body mass increased at both time points (1 yr: +2.2 +/- 0.4; 2 yr: +1.9 +/-
      0.5 mL.kg.min) and relative to AL. The CR group increased their treadmill test
      time and workload at 1 and 2 yr. Strength results in CR were similar, with
      decreases in absolute flexor and extensor strength, but increases when expressed
      relative to body mass. No changes were observed for VO2max expressed relative to
      lean body mass or leg lean mass. CONCLUSIONS: Two years of modest CR without a
      structured exercise component did not appear to compromise aerobic capacity in
      healthy nonobese adults. The clinical implications of the observed changes in
      VO2max and muscle strength will be important to explore in future studies.

PMID- 29045326
TI  - The Effects of Acute Interval Exercise and Strawberry Intake on Postprandial
      Lipemia.
AB  - PURPOSE: Raised postprandial triglycerides (TAG) and related oxidative stresses
      are strongly associated with increased cardiovascular disease risk. Acute
      exercise and strawberry ingestion independently ameliorate postprandial lipid
      excursions and oxidative stress. However, the combined effects of these lifestyle
      interventions are unknown. We investigated whether acute exercise and strawberry
      consumption improved postprandial responses to an oral fat tolerance test (OFTT)
      in overweight/obese males. METHODS: Overweight/obese adult males underwent four
      separate OFTT (73 g fat, 33 g carbohydrate) with blood sampled at baseline and
      hourly for 4 h after OFTT. Two OFTT contained 25 g freeze-dried strawberries and
      two contained strawberry flavoring (placebo). Participants performed 40 min of
      submaximal high-intensity interval cycling exercise 16 h before one strawberry
      and one placebo OFTT and rested before the remaining two OFTT. Serum TAG was
      analyzed, and TAG area under the curve (AUC) and incremental AUC (iAUC) were
      calculated. Oxidative stress markers were measured at baseline and 4 h.
      Differences between conditions (strawberry/placebo and exercise/rest) were
      assessed using repeated-measures ANOVA. RESULTS: Ten males (age = 31.5,
      interquartile range = 17.8 yr, body mass index = 29.9 +/- 1.8 kg.m) completed the
      study. TAG AUC was 1.5 mmol per 4 h.L lower for the exercise conditions compared
      with the rest conditions (95% confidence interval [CI] = -2.3 to -0.8 mmol per 4
      h.L, P = 0.001). TAG AUC was not different between strawberry and placebo
      conditions (95% CI = -1.3 to 0.6 mmol per 4 h.L, P = 0.475). TAG iAUC was 0.5
      mmol per 4 h.L greater for the strawberry compared with the placebo conditions
      (95% CI = 0.1 to 1.0 mmol per 4 h.L, P = 0.021). There were no changes in markers
      of lipid related oxidative stress (P > 0.05). CONCLUSION: Acute submaximal high
      intensity interval cycling exercise appears effective in reducing postprandial
      lipemia in overweight/obese adult males. However, strawberry ingestion did not
      improve postprandial TAG.

PMID- 29045327
TI  - Aging Impairs Whole-Body Heat Loss in Women under Both Dry and Humid Heat Stress.
AB  - PURPOSE: This study was designed to determine whether age-related impairments in
      whole-body heat loss, which are known to exist in dry heat, also occur in humid
      heat in women. METHODS: To evaluate this possibility, 10 young (25 +/- 4 yr) and
      10 older (51 +/- 7 yr) women matched for body surface area (young, 1.69 +/- 0.11;
      older, 1.76 +/- 0.14 m, P = 0.21) and peak oxygen consumption (VO2peak) (young,
      38.6 +/- 4.6; older, 34.8 +/- 6.6 mL.kg.min, P = 0.15) performed four 15-min
      bouts of cycling at a fixed metabolic heat production rate (300 W; equivalent to
      ~45% VO2peak), each separated by a 15-min recovery, in dry (35 degrees C, 20%
      relative humidity) and humid heat (35 degrees C, 60% relative humidity). Total
      heat loss (evaporative +/- dry heat exchange) and metabolic heat production were
      measured using direct and indirect calorimetry, respectively. Body heat storage
      was measured as the temporal summation of heat production and loss. RESULTS:
      Total heat loss was lower in humid conditions compared with dry conditions during
      all exercise bouts in both groups (all P < 0.05), resulting in 49% and 39%
      greater body heat storage in young and older women, respectively (both P < 0.01).
      Total heat loss was also lower in older women compared with young women during
      exercise bouts 1, 2 and 3 in dry heat (all P < 0.05) and bouts 1 and 2 in humid
      heat (both P < 0.05). Consequently, body heat storage was 29% and 16% greater in
      older women compared with young women in dry and humid conditions, respectively
      (both P < 0.05). CONCLUSIONS: Increasing ambient humidity reduces heat loss
      capacity in young and older women. However, older women display impaired heat
      loss relative to young women in both dry and humid heat, and may therefore be at
      greater risk of heat-related injury during light-to-moderate activity.

PMID- 29045328
TI  - Reversible Venting Stitch for Fenestrating Valve-less Glaucoma Shunts.
AB  - PURPOSE: The purpose of this is to describe a venting stitch modification for
      valveless glaucoma aqueous shunts and characterize early postoperative
      intraocular pressure (IOP) and glaucoma medication use following the
      modification. MATERIALS AND METHODS: Retrospective chart review of 61 sequential
      patients undergoing Baerveldt glaucoma implant (BGI)-350 implantation at the
      Doheny Eye Institute. Twenty-four patients received a glaucoma shunt with venting
      stitch modification (modified BGI) and 37 patients received an unmodified shunt
      (BGI-only). IOP, number of glaucoma medications, and number of hypotony cases
      (intraocular pressure <=5 mm Hg) were compared between the groups. T-tests were
      used for statistical analysis. RESULTS: At postoperative-day 1, mean IOP was
      significantly lower compared with preoperatively in the modified BGI group (14 mm
      Hg; reduced by 51%; P<0.0001) but not the BGI-only group (27 mm Hg; P=0.06). IOP
      difference between groups persisted till immediately before tube opening
      (P=0.005) and fewer IOP-lowering medications needed in the modified BGI group
      (P<0.0001). One case (4.2%) of postoperative hypotony was encountered with BGI
      modification, which resolved after the stitch was removed in clinic. CONCLUSIONS:
      The venting stitch valveless shunt modification allows for effective, reliable,
      and safe control of early postoperative IOP.

PMID- 29045330
TI  - Simultaneous Implantation of an Ahmed and Baerveldt Glaucoma Drainage Device for
      Uncontrolled Intraocular Pressure in Advanced Glaucoma: Comment.

PMID- 29045329
TI  - Hybrid Deep Learning on Single Wide-field Optical Coherence tomography Scans
      Accurately Classifies Glaucoma Suspects.
AB  - PURPOSE: Existing summary statistics based upon optical coherence tomographic
      (OCT) scans and/or visual fields (VFs) are suboptimal for distinguishing between
      healthy and glaucomatous eyes in the clinic. This study evaluates the extent to
      which a hybrid deep learning method (HDLM), combined with a single wide-field OCT
      protocol, can distinguish eyes previously classified as either healthy suspects
      or mild glaucoma. METHODS: In total, 102 eyes from 102 patients, with or
      suspected open-angle glaucoma, had previously been classified by 2 glaucoma
      experts as either glaucomatous (57 eyes) or healthy/suspects (45 eyes). The HDLM
      had access only to information from a single, wide-field (9*12 mm) swept-source
      OCT scan per patient. Convolutional neural networks were used to extract rich
      features from maps derived from these scans. Random forest classifier was used to
      train a model based on these features to predict the existence of glaucomatous
      damage. The algorithm was compared against traditional OCT and VF metrics.
      RESULTS: The accuracy of the HDLM ranged from 63.7% to 93.1% depending upon the
      input map. The retinal nerve fiber layer probability map had the best accuracy
      (93.1%), with 4 false positives, and 3 false negatives. In comparison, the
      accuracy of the OCT and 24-2 and 10-2 VF metrics ranged from 66.7% to 87.3%. The
      OCT quadrants analysis had the best accuracy (87.3%) of the metrics, with 4 false
      positives and 9 false negatives. CONCLUSIONS: The HDLM protocol outperforms
      standard OCT and VF clinical metrics in distinguishing healthy suspect eyes from
      eyes with early glaucoma. It should be possible to further improve this algorithm
      and with improvement it might be useful for screening.

PMID- 29045331
TI  - Test Conditions in Macular Visual Field Testing in Glaucoma.
AB  - PURPOSE: The purpose of this study is to evaluate the suitable visual field (VF)
      test conditions (target size, test type, and eccentricity) for the macular
      region, we investigated the correlations between the ganglion cell layer (GCL)
      thickness and 6 VF test results. METHODS: We tested 32 eyes of patients (61.1+/
      9.2 y) with preperimetric (6), early-stage (16), and moderate-stage (10)
      glaucoma. The VF tests included 3 SAP (the 10-2 HFA using SITA with target size
      III [HFA SITA (III)], full threshold with size III [HFA FULL (III)] and size I
      [HFA FULL (I)]) and 3 visual function-specific perimetry tests (the 10-2 SWAP, 10
      2 flicker, and 10-2 Humphrey Matrix). The GCL and inner plexiform layer (GCL+IPL)
      thickness was measured by Spectral Domain Optical Coherence Tomography (SD-OCT)
      with a macular 7*7 mm cube scan (3D OCT-2000, Topcon). The coefficient of
      determination (r) for the correlation between visual sensitivity and the GCL+IPL
      thickness was calculated for each test at eccentricities 0 to 5 degrees, 5 to 7
      degrees, and 7 to 10 degrees using linear and quadratic regressions. RESULTS: All
      6 tests showed the strongest correlation with the GCL+IPL thickness at 5 to 7
      degrees. The respective r (linear) and R (quadratic) for HFA SITA (III), HFA FULL
      (III), HFA FULL (I), SWAP, Flicker, and Matrix were (0.40, 0.50), (0.43, 0.53),
      (0.44, 0.46), (0.51, 0.51), (0.33, 0.34), and (0.52, 0.52). CONCLUSIONS: As
      compared with the frequently-used SAP with a size III, SAP with size I and the
      function-specific perimetry tests (especially the Matrix) could be more suitable
      for testing the macular region.

PMID- 29045332
TI  - Sutureless Deep Sclerectomy: A Preliminary Report.
AB  - This study describes a modification of deep sclerectomy, making it completely
      sutureless, with a 6-month follow-up period. This was a prospective pilot phase
      that included 24 eyes of 16 patients, 13 male individuals and 3 female
      individuals, with medically uncontrolled open-angle glaucomas despite maximally
      tolerated medical therapy. After excising the deep flap, no sutures are added to
      the superficial scleral flap or to the conjunctiva. A statistically significant
      reduction of the intraocular pressure was reported during all the follow-up
      visits without serious complications.

PMID- 29045333
TI  - Relationship Between Optic Nerve Head Drusen Volume and Structural and Functional
      Optic Nerve Damage.
AB  - PURPOSE: The purpose of this study is to assess the relationships between optic
      nerve head drusen (ONHD) volume, retinal nerve fiber layer (RNFL) thickness and
      visual field (VF) loss. METHODS: Patients with ONHD and no other ocular or
      systemic conditions that can affect RNFL or VF were enrolled. Serial enhanced
      depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve
      head (interval between scans, ~30 MUm) were obtained from each participant. ONHD
      volume was calculated for each eye by delineating the ONHD masses in each OCT B
      scan using 3-dimensional reconstruction software. RESULTS: A total of 47 eyes (28
      patients) with ONHD were included (mean age, 57+/-16 y). ONHD volume varied
      considerably [0.265+/-0.227 (range, 0.005 to 0.855)] mm. Linear and quadratic
      regression analyses demonstrated that ONHD volume is significantly associated
      with both global average RNFL thickness (linear R=0.531, quadratic R=0.557;
      P<0.001) and VF mean deviation (linear R=0.519, quadratic R=0.522; P<0.001). ONHD
      were most prevalent in the nasal quadrant (46 eyes, 98%), followed by superior,
      inferior and temporal quadrants [35 (74%), 30 (64%), and 16 (34%) eyes
      respectively]. The proportion of eyes with OCT RNFL defects (81%; 38/47 eyes) was
      significantly greater than that with VF defects (60%; 28/47 eyes) (P<0.001). RNFL
      defects were detected in 10 of the 19 eyes with no VF defects. RNFL defects were
      detected in all 28 eyes with VF defects. CONCLUSIONS: ONHD volume generally
      correlates with structural and functional optic nerve damage.

PMID- 29045335
TI  - Angiotensin-converting enzyme 2 and renal disease.
AB  - PURPOSE OF REVIEW: The renin-angiotensin system (RAS) is a pivotal player in the
      physiology and pathophysiology of cardiovascular and renal systems. Discovery of
      angiotensin-converting enzyme 2 (ACE2), capable of cleaving RAS effector peptide
      angiotensin (Ang) II into biologically active Ang-(1-7), has increased the
      complexity of our knowledge of the RAS. ACE2 expression is abundant in the kidney
      and is thought to provide protection against injury. This review emphasizes
      current experimental and clinical findings that examine ACE2 in the context of
      kidney injury and its potential therapeutic impact for treatment of kidney
      disease. RECENT FINDINGS: Clinical studies have reported upregulation of ACE2 in
      urine from diabetic patients, which may be reflective of pathological shedding of
      renal ACE2 as suggested by mechanistic experiments. Studies in experimental
      models have investigated the feasibility of pharmacological induction of ACE2 for
      improvement of renal function, inflammation, and fibrosis. SUMMARY: Emerging
      concepts about the RAS indicate that ACE2 is a critical regulator of angiotensin
      peptide metabolism and the pathogenesis of renal disease. Human recombinant ACE2
      is available and may be a practical clinical approach to enzyme replacement.
      Elucidating precise roles of ACE2 throughout disease progression will enrich our
      view of the RAS and help identify novel targets and appropriate strategies for
      intervention.

PMID- 29045334
TI  - Blood pressure parameters and morbid and mortal outcomes in nondialysis-dependent
      chronic kidney disease.
AB  - PURPOSE OF REVIEW: Observational and interventional studies provide conflicting
      evidence regarding optimal blood pressure (BP) control in persons with chronic
      kidney disease (CKD). Recent publications provide additional information to
      inform therapeutic decision-making. RECENT FINDINGS: Targeting SBP to less than
      120 mmHg, versus less than 140 mmHg, decreased cardiovascular events and all
      cause mortality in persons with nondiabetic CKD. A meta-analysis of trials
      testing blood pressure management among nondialysis-dependent CKD patients (15
      924 total patients) found more intensive therapies generally reduced mortality in
      all subgroups. Observational studies demonstrate that low SBP is associated with
      higher mortality in CKD. A recent report suggests that this is because of death
      from cardiovascular and noncardiovascular and nonmalignant causes, whereas higher
      BP is associated with death from cardiovascular causes. The shape of association
      between BP and cardiovascular and noncardiovascular events also appears to vary
      depending on baseline risk factors. Furthermore, BP measurement methodology may
      differ importantly between observational and interventional studies. SUMMARY: We
      review and summarize observational and interventional literature relating BP
      parameters to key clinical outcomes in persons with CKD. Apart from the inherent
      differences between these study designs, the disparate findings from trials and
      observational studies may be because of differences in patient characteristics
      and BP measurement techniques.

PMID- 29045336
TI  - Bile acid receptors and the kidney.
AB  - PURPOSE OF REVIEW: Bile acids act as activating signals of endogenous renal
      receptors: the nuclear receptor farnesoid X receptor (FXR) and the membrane-bound
      G protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5). In recent
      years, bile acids have emerged as important for renal pathophysiology by
      activating FXR and TGR5 and transcription factors relevant for lipid, cholesterol
      and carbohydrate metabolism, as well as genes involved in inflammation and renal
      fibrosis. RECENT FINDINGS: Activation of bile acid receptors has a promising
      therapeutic potential in prevention of diabetic nephropathy and obesity-induced
      renal damage, as well as in nephrosclerosis. During the past decade, progress has
      been made in understanding the biology and mechanisms of bile acid receptors in
      the kidney and in the development of specific bile acid receptor agonists.
      SUMMARY: In this review, we discuss current knowledge on the roles of FXR and
      TGR5 in the physiology of the kidney and the latest advances made in development
      and characterization of bile acid analogues that activate bile acid receptors for
      treatment of renal disease.

PMID- 29045337
TI  - Blood pressure regulation by the angiotensin type 1 receptor in the proximal
      tubule.
AB  - PURPOSE OF REVIEW: The renin-angiotensin system (RAS) plays a critical role in
      the pathogenesis of hypertension. Homeostatic actions of the RAS, such as
      increasing blood pressure (BP) and vasoconstriction, are mediated via type 1
      (AT1) receptors for angiotensin II. All components of the RAS are present in the
      renal proximal tubule, which reabsorbs the bulk of the glomerular filtrate,
      making this segment of the nephron a location of great interest for solute
      handling under RAS influence. This review highlights recent studies that
      illustrate the key role of renal proximal tubule AT1 receptors in BP regulation.
      RECENT FINDINGS: A variety of investigative approaches have demonstrated that
      angiotensin II signaling via AT1a receptors, specifically in the renal proximal
      tubule, is a major regulator of BP and sodium homeostasis. Reduction of proximal
      tubule AT1a receptors led to lower BPs, whereas overexpression generally caused
      increased BPs. SUMMARY: AT1a receptors in the proximal tubule are critical to the
      regulation of BP by the kidney and the RAS. The pattern of BP modulation is
      associated with alterations in sodium transporters. As a key site for sodium
      homeostasis, the renal proximal tubule could hence be a potential target in the
      treatment of hypertension.

PMID- 29045338
TI  - A clinical evaluation of the impact of the Bayesian penalized likelihood
      reconstruction algorithm on PET FDG metrics.
AB  - PURPOSE: The aim of this study was to evaluate the impact of using the Bayesian
      penalized likelihood (BPL) algorithm on a bismuth germanium oxide positron
      emission tomography (PET)/computed tomography (CT) system for F-FDG PET/CT exams
      in case of low injected activity and scan duration. MATERIALS AND METHODS: F-FDG
      respiratory gated PET/CT performed on 102 cancer patients, injected with ~2
      MBq/kg of F-FDG, were reconstructed using two algorithms: ordered subset
      expectation maximization (OSEM) and BPL. The signal-to-noise ratio (SNR) was
      calculated as the ratio of mean standard uptake value (SUV) over the standard
      deviation in a reference volume defined automatically in the liver. The peak SUV
      and volumes were also measured in lesions larger than 2 cm thanks to the
      automated segmentation method. RESULTS: On 85 respiratory gated patients, the
      median SNR was significantly higher with BPL (P<0.0001) and it is even better
      when the BMI of the patient increases (odds ratio=1.26).For the 55 lesions, BPL
      significantly increased the SUVpeak [difference: (-0.5; 1.4), median=0.4,
      P<0.0001] compared with OSEM in 83.6% of the cases. With BPL, the volume was
      lower in 61.8% of the cases compared with OSEM, but this was not statistically
      significant. CONCLUSION: The BPL algorithm improves the image quality and lesion
      contrast and appears to be particularly appropriate for patients with a high BMI
      as it improves the SNR. However, it will be important for patient follow-up or
      multicenter studies to use the same algorithm and preferably BPL.

PMID- 29045339
TI  - Blood pressure response to renal denervation is correlated with baseline blood
      pressure variability: a patient-level meta-analysis.
AB  - BACKGROUND: Sympathetic tone is one of the main determinants of blood pressure
      (BP) variability and treatment-resistant hypertension. The aim of our study was
      to assess changes in BP variability after renal denervation (RDN). In addition,
      on an exploratory basis, we investigated whether baseline BP variability
      predicted the BP changes after RDN. METHODS: We analyzed 24-h BP recordings
      obtained at baseline and 6 months after RDN in 167 treatment-resistant
      hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg)
      recruited at 11 expert centers. BP variability was assessed by weighted SD [SD
      over time weighted for the time interval between consecutive readings (SDiw)],
      average real variability (ARV), coefficient of variation, and variability
      independent of the mean (VIM). RESULTS: Mean office and 24-h BP fell by 15.4/6.6
      and 5.5/3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses,
      systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P
      <= 0.01) and 0.86/0.42 mmHg (P <= 0.05), respectively, whereas no significant
      changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw
      (P = 0.0006), ARV (P = 0.01), and VIM (P = 0.04) predicted the decrease in 24-h
      DBP but not 24-h SBP after RDN. CONCLUSION: RDN was associated with a decrease in
      BP variability independent of the BP level, suggesting that responders may derive
      benefits from the reduction in BP variability as well. Furthermore, baseline DBP
      variability estimates significantly correlated with mean DBP decrease after RDN.
      If confirmed in younger patients with less arterial damage, in the absence of the
      confounding effect of drugs and drug adherence, baseline BP variability may prove
      a good predictor of BP response to RDN.

PMID- 29045340
TI  - Cause of renal infarction: a retrospective analysis of 186 consecutive cases.
AB  - BACKGROUND: Renal infarction can cause abrupt and severe hypertension and less
      frequently renal failure. Renal infarction results from disruption of renal blood
      flow in the main ipsilateral renal artery or in a segmental branch. Underlying
      mechanism is either general, 'embolic' or 'thrombophilic', or local related to
      primary 'renal artery lesion'. It depends on various causes. In absence of an
      identified cause, renal infarction is classified as 'idiopathic'. Previous
      studies report a significant number of 'idiopathic' renal infarction. OBJECTIVE:
      The aim of this study was to analyze various renal infarction causes. METHODS:
      Between July 2000 and June 2015, 259 consecutive patients with renal infarction
      were admitted to our hospital center and retrospectively identified from weekly
      multidisciplinary round. Main clinical and biological characteristics were
      extracted from clinical data warehouse. Renal imaging was reviewed by two readers
      unaware of the diagnosis. RESULTS: Of 259 initially identified patients, 30 were
      excluded owing to a lack of imaging or clinical data and 43 because iatrogenic
      renal infarction. In the 186 studied patients, dissection was observed in 76
      patients (40.8%) and occlusion in 75 (40.3%). Renal infarction mechanisms were
      'renal artery lesion' (n = 151; 81.2%), 'embolic' (n = 17; 9.1%), 'thrombophilic'
      (n = 11; 5.9%) and 'idiopathic' (n = 7; 3.8%). Predominant renal artery lesions
      were atherosclerosis disease (n = 52; 34.4%) followed by dissecting hematoma (n =
      35; 23.2%) and fibromuscular dysplasia (n = 29; 19.2%). Right and left kidneys
      were equally involved. CONCLUSION: Renal artery lesion is the most frequent cause
      of renal infarction. This result underlines the need for extensive arterial
      exploration to identify the renal infarction mechanism and, in case of renal
      artery lesion, the underlying vascular disease.

PMID- 29045341
TI  - Effect of antihypertensive treatment on 24-h blood pressure variability: pooled
      individual data analysis of ambulatory blood pressure monitoring studies based on
      olmesartan mono or combination treatment.
AB  - OBJECTIVE: To evaluate the impact of olmesartan alone or combined with one to
      three antihypertensive drugs on 24-h blood pressure variability (BPV) and on
      distribution of BP reduction in a pooled individual data analysis of 10 double
      blind, randomized, ambulatory BP monitoring (ABPM) studies. METHODS: ABPMs were
      performed before and after 6-12 weeks of treatment with placebo (n = 119), active
      control monotherapy [n = 1195, angiotensin-converting enzyme inhibitors (ACEIs),
      angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers
      (DCCBs)] olmesartan monotherapy (n = 1410), active control dual combination [n =
      79, DCCB + thiazide diuretic (TD)], olmesartan dual combination (n = 637, DCCB or
      TD), and triple combination therapy (n = 102, DCCB+TD). 24-h BPV was calculated
      as unweighted or weighted SD of the mean BP, and average real variability. BP
      control was assessed by smoothness index and treatment-on-variability index.
      RESULTS: The greatest effect on 24-h systolic BPV/diastolic BPV was observed
      under olmesartan triple [-2.6/-1.9; -1.9/-1.3; -1.4/-1.3 mmHg] and active control
      dual combination [-1.8/-1.4; -1.9/-1.5; -1.2/-1.1 mmHg]. Smoothness indexes and
      treatment-on-variability indexes were significantly (P = 0.0001) higher under
      olmesartan dual (1.53/1.22, 1.67/1.29, 2.05/1.59), olmesartan triple (2.47/1.85,
      2.80/2.06, 3.64/2.67), or active control dual combination (1.70/1.26, 1.85/1.33,
      2.29/1.65) than under monotherapies (control: 0.86/0.73, 0.80/0.65, 1.01/0.82;
      olmesartan: 1.02/0.86, 0.95/0.78, 1.23/1.00). They were also greater in patients
      receiving high-dose olmesartan monotherapy or high-dose olmesartan dual
      combination than in the corresponding low-dose group. CONCLUSION: Olmesartan plus
      a DCCB and/or a TD produces a larger, more sustained, and smoother BP reduction
      than placebo and monotherapies, a desirable feature for a more effective
      prevention of the cardiovascular consequences of uncontrolled hypertension.

PMID- 29045342
TI  - Hypertensive disorders of pregnancy and postpartum readmission in the United
      States: national surveillance of the revolving door.
AB  - OBJECTIVES: Hypertensive disorders of pregnancy (HDP) represent the most common
      cause of maternal-fetal morbidity and mortality. Yet, the prevalence and cost of
      postpartum (42-day) readmission (PPR) among HDP-complicated pregnancies in the
      United States remains unknown. This study provides national prevalence and cost
      estimates of HDP, and examine factors associated with potentially preventable PPR
      following HDP-complicated pregnancies. METHOD: The 2013 and 2014 Nationwide
      Readmissions Databases were used to investigate HDP and PPR among delivery
      hospitalizations to women aged 15-49 years. PPR rates, length of stay, and costs
      were stratified by four HDP subtypes based on timing and severity of their
      condition. Survey logistic regression was employed to generate adjusted odds
      ratios for the association between HDP and PPR. RESULT: In 2013 and 2014, there
      were 6.3 million delivery hospitalizations; 666 506 (10.6%) were complicated by
      HDP. Annually, HDP was responsible for higher rates of potentially preventable
      PPR. Among HDP-complicated pregnancies, the 42-day all-cause PPR rate ranged from
      2.5% (gestational hypertension) to 4.6% (superimposed preeclampsia/eclampsia).
      Compared with normotensive pregnancies, HDP resulted in an excess 404 800
      hospital days and inpatient care costs of $731 million. Even after controlling
      for patient-level and hospital-level confounders, all hypertensive subgroups
      continued to have at least two-fold, statistically significant, increased odds of
      potentially preventable PPR. CONCLUSION: HDP is associated with increased risk of
      PPR and substantial medical costs. Preventive efforts should be made to identify
      women at increased risk of PPR during hospitalization so that transition care
      intervention can be initiated.

PMID- 29045343
TI  - Brachial-ankle pulse wave velocity compared with mean arterial pressure and pulse
      pressure in risk stratification in a Chinese population.
AB  - BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) can be easily measured in
      an observer-independent way, but lacks robust population-based validation in
      terms of fatal combined with nonfatal outcomes. METHOD: To address this issue, we
      studied 4251 Chinese randomly recruited Gaoyou County (54.1% women; mean age,
      52.1). RESULTS: In the whole study population, mean values were 102.4 mmHg for
      mean arterial pressure (MAP), 51.1 mmHg for pulse pressure, and 14.8 m/s for
      baPWV. Over 4.4 years (median), 74 participants experienced a fatal or nonfatal
      cardiovascular event and 44 a stroke. In multivariable-adjusted Cox regression,
      standardized hazard ratios expressing the risk of a composite cardiovascular
      endpoint were 1.77 (95% confidence interval, 1.43-2.20), 1.37 (1.14-1.64) and
      1.50 (1.26-1.78) for MAP, PP and baPWV, respectively; the corresponding hazard
      ratios for stroke were 1.82 (1.39-2.38), 1.39 (1.12-1.74) and 1.53 (1.25-1.89).
      baPWV did not add to the prediction of cardiovascular events or stroke by MAP
      (hazard ratios for baPWV, 1.25 and 1.27, respectively; P >= 0.053) but refined
      models including PP (hazard ratios, 1.42 and 1.45; P <= 0.0033). The optimized
      baPWV threshold, obtained by maximizing Youden's index (16.7 m/s), increased the
      integrated discrimination improvement over and beyond MAP (+1.27%; P = 0.021) and
      PP (+1.37%; P = 0.038) for the cardiovascular outcome, but not stroke, and
      increased the net reclassification improvement for both endpoints (>=42.2%; P <=
      0.004). CONCLUSION: With fatal and nonfatal cardiovascular and cerebrovascular
      endpoints as outcome, baPWV marginally increases risk stratification over and
      beyond MAP, but is a better predictor than PP. A threshold of 16.7 m/s might be
      used in Chinese populations.

PMID- 29045344
TI  - Atrial fibrillation and cardiac resynchronization therapy.
AB  - PURPOSE OF REVIEW: Atrial fibrillation and heart failure are commonly encountered
      in current clinical practice. This review aims to revisit the complex interaction
      of these two common situations and the best treatment whenever both occurs,
      especially focusing on heart failure patients undergoing cardiac
      resynchronization therapy (CRT). RECENT FINDINGS: It has been recently confirmed
      that in patients undergoing cardiac resynchronization therapy, 100% biventricular
      pacing percentage should be pursued. Large observational studies confirmed that
      atrioventricular junction ablation is very often the only way to gain 100%
      biventricular pacing in atrial fibrillation. SUMMARY: On the basis of the recent
      observational extensive data, in patients presenting intermediate or elevated
      atrial tachycardia-atrial fibrillation burden, atrioventricular junction ablation
      may represent a fundamental tool to achieve full CRT delivery, thus, conferring
      marked improvements in global cardiac function, and by extension, in survival.
      Atrial fibrillation patients should not be excluded from CRT, provided that
      maximal biventricular pacing is warranted.

PMID- 29045345
TI  - Leadless cardiac pacemakers: present and the future.
AB  - PURPOSE OF REVIEW: Pacing technology for many decades has been composed of a
      generator attached to leads that are usually transvenous. Recently, leadless
      pacemakers have been studied in clinical settings and now available for use in
      many countries. This includes the single-component Nanostim Leadless Cardiac
      Pacemaker and Micra Transcatheter Pacing System, as well as the multicomponent
      Wireless Stimulation Endocardial system. RECENT FINDINGS: Clinical studies in
      single-component leadless pacing technology has shown that they can be
      successfully implanted with minimal complications. The follow-up studies also
      seem to confirm the findings from the initial clinical trials. These systems
      offer some advantages over a traditional pacing system comprised of a
      subcutaneous generator and transvenous leads. SUMMARY: In many ways, these
      leadless systems are disruptive technologies that are changing the traditional
      pacemaker concept and preferred for some patients. Ongoing research is needed to
      better assess their long-term function, safety, and end-of-life strategies. In
      the future, multichamber leadless pacing is expected to be developed and perhaps
      obviating the need for transvenous leads and their associated complications.

PMID- 29045346
TI  - Autoimmune Hepatitis and Autoimmune Hepatitis Overlap With Sclerosing
      Cholangitis: Immunophenotype Markers in Children and Adolescents.
AB  - OBJECTIVE: The pathophysiology of autoimmune hepatitis (AIH) may involve the
      activation of immune cells and changes in the expression of cellular markers. The
      aim of the present study was to characterize the immunophenotype markers of
      lymphocytes and monocytes in the peripheral blood of children and adolescents
      with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome
      [OS]). METHODS: This is a cross-sectional study of 20 children and adolescents
      diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included
      as controls. Flow cytometric analysis was used to identify markers of
      inflammation and autoimmunity. RESULTS: The total number of CD4 T cells was
      higher in the AIH patients compared with the controls. The number of CD4 T cells
      expressing CCR3 and CD28 was higher in the AIH group than in the control group.
      CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly
      expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression
      was higher in both groups of patients. Patients with OS had the highest
      expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR)
      was less expressed in both groups of patients. CONCLUSIONS: Complex phenotype
      features may be involved in the pathophysiology of AIH, accounting for changes in
      immune system regulation mechanisms. In conclusion, even after good response to
      treatment, patients still have immune activity signals at the cellular level.

PMID- 29045347
TI  - Reduction of Recurrence Risk of Pancreatitis in Cystic Fibrosis With Ivacaftor:
      Case Series.
AB  - The effect of ivacaftor in patients with cystic fibrosis (CF) with recurrent
      pancreatitis is unknown. We conducted a multicenter retrospective study of
      patients with CF taking ivacaftor who had a history of recurrent pancreatitis.
      During the first 3 months of therapy, only 1 of the 6 patients had an episode of
      pancreatitis, which was managed on an outpatient basis. Between 3 and 12 months
      on ivacaftor therapy, none of the patients had recurrence of pancreatitis or
      required hospitalization. The use of ivacaftor was associated with a reduced
      frequency and recurrence rate of pancreatitis in patients with CF.

PMID- 29045348
TI  - Choice of Endoscopic Procedure in Children With Clinically Suspected
      Gastrointestinal Graft-versus-host Disease.
AB  - OBJECTIVES: Gastrointestinal graft-versus-host disease (GI-GVHD) is a potentially
      life-threatening complication after hematopoietic stem cell transplantation.
      Symptoms indicating GI-GVHD motivates endoscopy with biopsy sampling and
      histopathological confirmation. Optimal extent of endoscopy in children is,
      however, presently unknown. Therefore, we aimed to evaluate whether biopsies from
      the rectosigmoid area versus the rest of the colon/ileocolon with or without
      biopsies from simultaneous upper endoscopy, were equally reliable for detection
      of GI-GVHD and relevant differential diagnoses. METHODS: Retrospective
      multicenter study based on histopathological re-evaluation of biopsies and
      hospital record data, collected from children with suspected GI-GVHD. RESULTS:
      Forty-four children with 51 endoscopic occasions (81 procedures) were included.
      Thirty-nine of 51 (76.5%) were diagnosed as GI-GVHD, 14 (27.4%) received a
      differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity,
      that is, simultaneous detection of a differential diagnosis and GI-GVHD, was
      observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent
      differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and
      esophagogastroduodenal areas. Sensitivity for detection of GI-GVHD in biopsies
      collected from rectosigmoid-ileocolonic-, rectosigmoid-, or
      esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4%
      when the latter 2 were merged. The difference, nondetected GI-GVHD in the
      rectosigmoid area versus detected elsewhere in the GI tract, was statistically
      significant (P = 0.03). CONCLUSIONS: Biopsies collected from the rectosigmoid
      area solely were not optimal for detection of pediatric GI-GVHD. When biopsy
      sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity
      for GI-GVHD was, however, equally high as for ileocolonoscopy or full upper and
      lower endoscopy.

PMID- 29045349
TI  - Male-specific Association Between Fat-Free Mass Index and Fecal Microbiota in 2-
      to 3-Year-Old Australian Children.
AB  - OBJECTIVES: Maturation of the gut microbiota has been shown to influence
      childhood growth, whereas alterations in microbiota composition are proposed to
      be causally related to the development of overweight and obesity. The objective
      of this study is to explore the association between microbiota profile, body
      size, and body composition in young children. METHODS: Fecal microbiota was
      examined by 16S rRNA gene sequencing, whereas body composition was assessed using
      the deuterium oxide dilution technique in a cohort of 37 well-nourished 2- to 3
      year-old Australian children. RESULTS: Microbiota composition (weighted UniFrac
      distance) was shown to be significantly associated with FFMI (fat-free mass
      index) z score (P = 0.027, adonis) in boys but not girls. In boys, FFMI z score
      was significantly correlated with the relative abundance of an OUT (Operational
      Taxonomic Unit) belonging to the Ruminococcaceae family (Rho = 0.822, P < 0.001,
      pFDR (false discovery rate adjusted P value) = 0.002, n = 18). At a FDR <0.2,
      FFMI z score in boys was positively associated with the relative abundance of OTU
      related to Dorea formicigenerans and Faecalibacterium prausnitzii and negatively
      correlated to an OTU related to Bacteroides cellulosilyticus. CONCLUSIONS: These
      results suggest that previously reported associations between microbiota
      composition and body size may be driven by an association with fat-free mass,
      particularly in males.

PMID- 29045350
TI  - Donor Human Milk and Fortifier Use in United States Level 2, 3, and 4 Neonatal
      Care Hospitals.
AB  - OBJECTIVE: In 2011, the United States Surgeon General issued a call to action to
      "identify and address obstacles to greater availability of safe banked donor milk
      for fragile infants." The purpose of the present study is to analyze patterns in
      donor human milk (DHM) and fortifier use in level 2, 3, and 4 neonatal facilities
      in 2015 and to identify factors associated with nonuse. METHODS: Data from the
      2015 Maternity Practices in Infant Nutrition and Care survey, conducted by the
      Center for Disease Control and Prevention, were analyzed for questions about
      feeding practices within neonatal hospitals. RESULTS: The percentage of neonatal
      facilities that reported using DHM in 2015 was 38.3%, up 74% from 2011. The
      majority of level 3 and level 4 facilities reported using DHM (65.7% and 73.3%,
      respectively) and fortifiers (96.1% and 91.9%, respectively). Within DHM-using
      facilities, a wide range of DHM feeding patterns was reported. The prevalence of
      DHM use was higher in facilities that had the highest rates of mother's own milk
      feedings (P < 0.001), in facilities that were participating in the Baby Friendly
      Hospital Initiative (P < 0.001), and in facilities that were in a state with an
      operating milk bank (P < 0.001). CONCLUSIONS: DHM use continues to increase in
      advanced care neonatal settings, with significant difference based on acuity
      level, facility size, breast-feeding culture, and proximity to a milk bank.
      Geographic gaps in DHM use provide the opportunity for targeted efforts to
      improve access.

PMID- 29045351
TI  - Awareness and Implementation of the 2014 ESPGHAN/NASPGHAN Guideline for Childhood
      Functional Constipation.
AB  - OBJECTIVE: The aim of the study was to assess whether physicians approach
      children with functional constipation according to the 2014 European Society of
      Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)/North American
      Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)
      guideline. METHODS: We invited pediatricians and pediatric gastroenterologists in
      the Netherlands and the United States to participate in this anonymous survey
      using a self-developed questionnaire containing 19 multiple choice questions
      concerning evaluation and treatment of children with constipation. RESULTS: We
      included 328 physicians (67% from the United States, 34% from the Netherlands).
      The majority of US responders (53%) worked in primary care, whereas all Dutch
      responders worked in a hospital. In total, 31% of responders were not familiar
      with the guideline (38% US responders vs 16% Dutch responders, P < 0.001).
      Perianal inspection was frequently ("often" or "always" on a 5-point Likert
      scale) conducted by 78% of responders. Digital rectal examination was frequently
      done by 42%. Inquiry about sexual abuse was made by 18%. Commonly reported
      reasons for omitting these items were perceived patient or parental discomfort.
      Most frequently implemented initial nonpharmacological interventions included a
      toilet training program (89%), optimizing fluid and fiber intake (86% and 81%), a
      defecation diary (62%), and a reward system (60%). Polyethylene glycol was the
      most prescribed medication for disimpaction (68%) and maintenance treatment (57%
      for infants, 97% for children >=1 year). CONCLUSIONS: Many responders were not
      familiar with the ESPGHAN/NASPGHAN guideline for functional constipation.
      Nonetheless, therapeutic decisions correlated fairly well with recommendations
      from the guideline, especially for children 1 year of age or older. Guideline
      awareness and adherence remain to be improved. Future studies should focus on
      exploring strategies to improve guideline implementation through the development
      of digital learning tools.

PMID- 29045352
TI  - Impact of Race and Ethnicity on Outcomes for Children Waitlisted for Pediatric
      Liver Transplantation.
AB  - OBJECTIVE: African Americans and other minorities are known to face barriers to
      health care influencing their access to organ transplantation but it is not known
      whether these barriers exist among pediatric liver transplant waitlist
      candidates. We sought to determine whether outcomes on the waitlist (ie,
      mortality, deceased donor liver transplantation [DDLT], and living-donor liver
      transplantation [LDLT]) varied by race/ethnicity. METHODS: National registry data
      were studied to estimate the race/ethnicity-specific risk of waitlist mortality,
      DDLT and LDLT in children (<18 years) waitlisted between March 2002 and March
      2015. RESULTS: There was no evidence of racial/ethnic disparities in waitlist
      mortality. Compared to Caucasians, LDLT varied by race/ethnicity, with only 6.7%
      African Americans and 10.3% Hispanic children receiving LDLT compared with 12.4%
      Caucasian, 13.3% Asian, and 9.4% mix/other children. In an adjusted Cox
      proportional hazards model, African Americans were half as likely as Caucasians
      to use LDLT (hazard ratio [HR]: 0.410.550.73) but had similar use of DDLT (HR:
      0.981.061.16). In a model that considered mortality, DDLT, and LDLT as competing
      risks, African Americans had significantly reduced incidence of LDLT (subhazard
      ratio [sHR]: 0.410.560.75) compared to Caucasians, but increased use of DDLT
      (sHR: 1.061.161.26). CONCLUSIONS: Compared to Caucasian children, African
      American children are less likely to use LDLT but have higher rates of DDLT and
      similar survival on the waitlist. Additional research is necessary to understand
      the clinical and socioeconomic factors contributing to lower utilization of LDLT
      among African-American children awaiting transplantation.

PMID- 29045353
TI  - Impaired IL-10 Receptor-mediated Suppression in Monocyte From Patients With Crohn
      Disease.
AB  - OBJECTIVES: Interleukin-10 (IL-10) is an immunoregulatory cytokine that has a
      central role in suppressing proinflammatory responses. Patients with deleterious
      mutations in interleukin (IL)-10 or IL-10 receptor (IL-10R) genes develop severe
      colitis and perianal disease in the first months of life. Whether IL-10R
      expression and signaling in pediatric- or adult-onset Crohn disease (CD) are
      altered is unknown. The objective of this study was to characterize IL-10R
      expression and IL-10R-mediated suppression in patients with CD. METHODS:
      Monocytes were sorted from peripheral blood mononuclear cells of patients with CD
      and control subjects. IL-10R expression was determined by flow cytometry.
      Monocytes were stimulated with lipopolysaccharide (LPS) for 3 hours in the
      presence of different concentrations of IL-10 to determine IL-10-mediated
      suppression of tumor necrosis factor alpha production. Signaling through the IL
      10R was evaluated by quantifying STAT3 phosphorylation in response to IL-10
      stimulation. RESULTS: Forty-two subjects were enrolled in this study: 19 with CD
      and 23 controls. Stimulation of monocytes with LPS markedly increased IL-10R
      expression in both groups but to a much lower extent in patients with CD. In
      addition, IL-10-mediated suppression of TNFalpha production upon LPS stimulation
      and IL-10-induced STAT3 phosphorylation were attenuated in patients with CD
      versus controls. Finally, LPS-stimulated monocytes from patients with CD secreted
      significantly lower quantities of IL-10, compared with control monocytes.
      CONCLUSIONS: IL-10R expression and signaling are decreased in monocytes from
      patients with CD. Additional studies are required to assess whether similar
      patterns occur in other innate immune cells, especially in the gut, and whether
      disease activity, medical therapy, and genetic factors modulate these findings.

PMID- 29045354
TI  - The Case for Thoughtful Prescribing of Proton Pump Inhibitors in Infants.

PMID- 29045355
TI  - Complexity of Chronic Conditions' Impact on End-of-Life Expense Trajectories of
      Medicare Decedents.
AB  - OBJECTIVE: The aim of this study is to determine if the pattern of monthly
      medical expense can be used to identify individuals at risk of dying, thus
      supporting providers in proactively engaging in advanced care planning
      discussions. BACKGROUND: Identifying the right time to discuss end of life can be
      difficult. Improved predictive capacity has made it possible for nurse leaders to
      use large data sets to guide clinical decision making. METHODS: We examined the
      patterns of monthly medical expense of Medicare beneficiaries with life-limiting
      illness during the last 24 months of life using analysis of variance, t tests,
      and stepwise hierarchical linear modeling. RESULTS: In the final year of life,
      monthly medical expense increases rapidly for all disease groupings and forms
      distinct patterns of change. CONCLUSION: Type of condition can be used to
      classify decedents into distinctly different cost trajectories. Conditions
      including chronic disease, system failure, or cancer may be used to identify
      patients who may benefit from supportive care.

PMID- 29045356
TI  - Addressing Safe Opioid Monitoring Practices Using an Interprofessional Approach.
AB  - OBJECTIVE: The aims of the project are to increase knowledge related to opioids
      and improve adherence to evidence-based interventions for sedation monitoring and
      assessment in adult inpatients receiving opioids for pain through delivery of an
      interprofessional online program. BACKGROUND: Preventable opioid-induced
      respiratory depression is a patient safety risk in hospitals. Sedation and
      respiratory assessment and monitoring guidelines and tools are available to
      improve practice. METHODS: An interprofessional team identified organization
      specific drivers of opioid-induced sedation and respiratory depression using
      process improvement methodology, developed interventions, and evaluated clinician
      opioid knowledge and documentation practice. RESULTS: Opioid knowledge survey
      responses improved after the interventions. Audits showing improved appropriate
      documentation by RNs of the correct sedation scale were performed over 2 separate
      3-month periods. CONCLUSIONS: Clinicians demonstrated increased knowledge about
      newly adopted sedation and monitoring practices targeted to prevent opioid
      induced respiratory depression.

PMID- 29045357
TI  - Clinical Effectiveness and Cost of a Hospital-Based Fall Prevention Intervention:
      The Importance of Time Nurses Spend on the Front Line of Implementation.
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical effectiveness and
      incremental net cost of a fall prevention intervention that involved hourly
      rounding by RNs at 2 hospitals. BACKGROUND: Minimizing in-hospital falls is a
      priority, but little is known about the value of fall prevention interventions.
      METHODS: We used an uncontrolled before-after design to evaluate changes in fall
      rates and time use by RNs. Using decision-analytical models, we estimated
      incremental net costs per hospital per year. RESULTS: Falls declined at 1
      hospital (incidence rate ratio [IRR], 0.47; 95% confidence interval [CI], 0.26
      0.87; P = .016), but not the other (IRR, 0.83; 95% CI, 0.59-1.17; P = .28). Cost
      analyses projected a 67.9% to 72.2% probability of net savings at both hospitals
      due to unexpected declines in the time that RNs spent in fall-related activities.
      CONCLUSIONS: Incorporating fall prevention into hourly rounds might improve
      value. Time that RNs invest in implementing quality improvement interventions can
      equate to sizable opportunity costs or savings.

PMID- 29045359
TI  - Scaling the heights.

PMID- 29045360
TI  - Steeped in science.

PMID- 29045358
TI  - Evaluating the Rotation Correction of the Main Thoracic Curve in Severe
      Adolescent Idiopathic Scoliosis: Bending and Traction vs. Fulcrum - A Preliminary
      Report.
AB  - BACKGROUND Flexibility evaluation methods were only used to assess the changes of
      coronal Cobb angle in patients with adolescent idiopathic scoliosis (AIS). Little
      attention was attached to the vertebral rotation in these methods. MATERIAL AND
      METHODS 21 patients with severe adolescent idiopathic scoliosis were enrolled in
      this study. Coronal flexibility and rotation correction were compared on the
      supine bending, traction and fulcrum bending radiographs. The apical vertebral
      body rib ratio (AVB-R), and Perdriolle rotation angles were used to measure the
      rotation of the main thoracic curve. Statistical analysis was performed with one
      way Analysis of Variance(ANOVA). Correlations between postoperative AVB-R and AVB
      R in supine bending, traction and fulcrum bending radiographs were assessed
      utilizing the Linear Regression. RESULTS There were trends towards increased
      coronal flexibility in fulcrum bending versus traction versus supine bending, but
      there were no significant differences due to the limited sample size. And all
      were significantly lower than postoperative correction. The correction of AVB-R
      at traction and supine bending radiographs were significantly better than fulcrum
      bending, however, all were significantly lower than postoperative correction.
      Correction of Perdriolle rotation angle at traction radiograph was best among
      these methods. A univariant linear regression analysis showed a strong linear
      correlation between the postoperative AVB-R and the AVB-R in the traction
      radiograph. CONCLUSIONS As to patients with severe AIS, the coronal plane
      flexibility evaluated at the fulcrum bending radiograph is superior to that at
      the traction radiograph. This may be explained by the measurement errors induced
      by the better derotation capacity at the traction radiograph. Rotation correction
      evaluated at the traction radiograph proves better than the fulcrum bending
      radiographs, showing a linear correlation with the postoperative correction.

PMID- 29045361
TI  - On the biotech block.

PMID- 29045362
TI  - A league of their own.

PMID- 29045363
TI  - Comment: Where the streets are paved with ideas.

PMID- 29045364
TI  - Spain's science rivalry.

PMID- 29045365
TI  - A guide to the Nature Index.

PMID- 29045366
TI  - Metropolis of minds.

PMID- 29045367
TI  - Destination Daejeon.

PMID- 29045368
TI  - Neighbours in knowledge.

PMID- 29045369
TI  - Amyotrophic lateral sclerosis.

PMID- 29045370
TI  - Genetics: The hexanucleotide hex.

PMID- 29045371
TI  - Fundraising: The Ice Bucket Challenge delivers.

PMID- 29045372
TI  - Machine learning: Calculating disease.

PMID- 29045373
TI  - Non-Familial ALS: A tangled web.

PMID- 29045375
TI  - Perspective: Untangling the ALS X-Files.

PMID- 29045374
TI  - Perspective: Don't keep it in the family.

PMID- 29045378
TI  - Ubiquitin biology: Unraveling the chain.

PMID- 29045376
TI  - Drug therapy: On the treatment trail for ALS.

PMID- 29045380
TI  - Host-microbe interactions: Aiming at GPCRs.

PMID- 29045381
TI  - Bacterial cell wall: Phages breaking free.

PMID- 29045382
TI  - Biomaterials: Cotton gets superpowers.

PMID- 29045379
TI  - Discovery of new GPCR ligands to illuminate new biology.
AB  - Although a plurality of drugs target G-protein-coupled receptors (GPCRs), most
      have emerged from classical medicinal chemistry and pharmacology programs and
      resemble one another structurally and functionally. Though effective, these drugs
      are often promiscuous. With the realization that GPCRs signal via multiple
      pathways, and with the emergence of crystal structures for this family of
      proteins, there is an opportunity to target GPCRs with new chemotypes and confer
      new signaling modalities. We consider structure-based and physical screening
      methods that have led to the discovery of new reagents, focusing particularly on
      the former. We illustrate their use against previously untargeted or orphan
      GPCRs, against allosteric sites, and against classical orthosteric sites that
      selectively activate one downstream pathway over others. The ligands that emerge
      are often chemically novel, which can lead to new biological effects.

PMID- 29045383
TI  - Drug discovery: Controlling protein SUMOylation.

PMID- 29045384
TI  - Disorder in convergent floral nanostructures enhances signalling to bees.
AB  - Diverse forms of nanoscale architecture generate structural colour and perform
      signalling functions within and between species. Structural colour is the result
      of the interference of light from approximately regular periodic structures; some
      structural disorder is, however, inevitable in biological organisms. Is this
      disorder functional and subject to evolutionary selection, or is it simply an
      unavoidable outcome of biological developmental processes? Here we show that
      disordered nanostructures enable flowers to produce visual signals that are
      salient to bees. These disordered nanostructures (identified in most major
      lineages of angiosperms) have distinct anatomies but convergent optical
      properties; they all produce angle-dependent scattered light, predominantly at
      short wavelengths (ultraviolet and blue). We manufactured artificial flowers with
      nanoscale structures that possessed tailored levels of disorder in order to
      investigate how foraging bumblebees respond to this optical effect. We conclude
      that floral nanostructures have evolved, on multiple independent occasions, an
      effective degree of relative spatial disorder that generates a photonic signature
      that is highly salient to insect pollinators.

PMID- 29045385
TI  - USP7 small-molecule inhibitors interfere with ubiquitin binding.
AB  - The ubiquitin system regulates essential cellular processes in eukaryotes.
      Ubiquitin is ligated to substrate proteins as monomers or chains and the topology
      of ubiquitin modifications regulates substrate interactions with specific
      proteins. Thus ubiquitination directs a variety of substrate fates including
      proteasomal degradation. Deubiquitinase enzymes cleave ubiquitin from substrates
      and are implicated in disease; for example, ubiquitin-specific protease-7 (USP7)
      regulates stability of the p53 tumour suppressor and other proteins critical for
      tumour cell survival. However, developing selective deubiquitinase inhibitors has
      been challenging and no co-crystal structures have been solved with small
      molecule inhibitors. Here, using nuclear magnetic resonance-based screening and
      structure-based design, we describe the development of selective USP7 inhibitors
      GNE-6640 and GNE-6776. These compounds induce tumour cell death and enhance
      cytotoxicity with chemotherapeutic agents and targeted compounds, including PIM
      kinase inhibitors. Structural studies reveal that GNE-6640 and GNE-6776 non
      covalently target USP7 12 A distant from the catalytic cysteine. The compounds
      attenuate ubiquitin binding and thus inhibit USP7 deubiquitinase activity. GNE
      6640 and GNE-6776 interact with acidic residues that mediate hydrogen-bond
      interactions with the ubiquitin Lys48 side chain, suggesting that USP7
      preferentially interacts with and cleaves ubiquitin moieties that have free Lys48
      side chains. We investigated this idea by engineering di-ubiquitin chains
      containing differential proximal and distal isotopic labels and measuring USP7
      binding by nuclear magnetic resonance. This preferential binding protracted the
      depolymerization kinetics of Lys48-linked ubiquitin chains relative to Lys63
      linked chains. In summary, engineering compounds that inhibit USP7 activity by
      attenuating ubiquitin binding suggests opportunities for developing other
      deubiquitinase inhibitors and may be a strategy more broadly applicable to
      inhibiting proteins that require ubiquitin binding for full functional activity.

PMID- 29045387
TI  - Photobiology: How flowers get the blues to lure bees.

PMID- 29045386
TI  - Mfsd2b is essential for the sphingosine-1-phosphate export in erythrocytes and
      platelets.
AB  - Sphingosine-1-phosphate (S1P), a potent signalling lipid secreted by red blood
      cells and platelets, plays numerous biologically significant roles. However, the
      identity of its long-sought exporter is enigmatic. Here we show that the major
      facilitator superfamily transporter 2b (Mfsd2b), an orphan transporter, is
      essential for S1P export from red blood cells and platelets. Comprehensive
      lipidomic analysis indicates a dramatic and specific accumulation of S1P species
      in Mfsd2b knockout red blood cells and platelets compared with that of wild-type
      controls. Consistently, biochemical assays from knockout red blood cells,
      platelets, and cell lines overexpressing human and mouse Mfsd2b proteins
      demonstrate that Mfsd2b actively exports S1P. Plasma S1P level in knockout mice
      is significantly reduced by 42-54% of that of wild-type level, indicating that
      Mfsd2b pathway contributes approximately half of the plasma S1P pool. The
      reduction of plasma S1P in knockout mice is insufficient to cause blood vessel
      leakiness, but it does render the mice more sensitive to anaphylactic shock.
      Stress-induced erythropoiesis significantly increased plasma S1P levels and
      knockout mice were sensitive to these treatments. Surprisingly, knockout mice
      exhibited haemolysis associated with red blood cell stomatocytes, and the
      haemolytic phenotype was severely increased with signs of membrane fragility
      under stress erythropoiesis. We show that S1P secretion by Mfsd2b is critical for
      red blood cell morphology. Our data reveal an unexpected physiological role of
      red blood cells in sphingolipid metabolism in circulation. These findings open
      new avenues for investigating the signalling roles of S1P derived from red blood
      cells and platelets.

PMID- 29045388
TI  - Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.
AB  - The skin barrier is the body's first line of defence against environmental
      assaults, and is maintained by epithelial stem cells (EpSCs). Despite the
      vulnerability of EpSCs to inflammatory pressures, neither the primary response to
      inflammation nor its enduring consequences are well understood. Here we report a
      prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier
      restoration after subsequent tissue damage. This functional adaptation does not
      require skin-resident macrophages or T cells. Instead, EpSCs maintain chromosomal
      accessibility at key stress response genes that are activated by the primary
      stimulus. Upon a secondary challenge, genes governed by these domains are
      transcribed rapidly. Fuelling this memory is Aim2, which encodes an activator of
      the inflammasome. The absence of AIM2 or its downstream effectors, caspase-1 and
      interleukin-1beta, erases the ability of EpSCs to recollect inflammation.
      Although EpSCs benefit from inflammatory tuning by heightening their
      responsiveness to subsequent stressors, this enhanced sensitivity probably
      increases their susceptibility to autoimmune and hyperproliferative disorders,
      including cancer.

PMID- 29045390
TI  - The dynamics of molecular evolution over 60,000 generations.
AB  - The outcomes of evolution are determined by a stochastic dynamical process that
      governs how mutations arise and spread through a population. However, it is
      difficult to observe these dynamics directly over long periods and across entire
      genomes. Here we analyse the dynamics of molecular evolution in twelve
      experimental populations of Escherichia coli, using whole-genome metagenomic
      sequencing at five hundred-generation intervals through sixty thousand
      generations. Although the rate of fitness gain declines over time, molecular
      evolution is characterized by signatures of rapid adaptation throughout the
      duration of the experiment, with multiple beneficial variants simultaneously
      competing for dominance in each population. Interactions between ecological and
      evolutionary processes play an important role, as long-term quasi-stable
      coexistence arises spontaneously in most populations, and evolution continues
      within each clade. We also present evidence that the targets of natural selection
      change over time, as epistasis and historical contingency alter the strength of
      selection on different genes. Together, these results show that long-term
      adaptation to a constant environment can be a more complex and dynamic process
      than is often assumed.

PMID- 29045389
TI  - Molecular basis of USP7 inhibition by selective small-molecule inhibitors.
AB  - Ubiquitination controls the stability of most cellular proteins, and its
      deregulation contributes to human diseases including cancer. Deubiquitinases
      remove ubiquitin from proteins, and their inhibition can induce the degradation
      of selected proteins, potentially including otherwise 'undruggable' targets. For
      example, the inhibition of ubiquitin-specific protease 7 (USP7) results in the
      degradation of the oncogenic E3 ligase MDM2, and leads to re-activation of the
      tumour suppressor p53 in various cancers. Here we report that two compounds,
      FT671 and FT827, inhibit USP7 with high affinity and specificity in vitro and
      within human cells. Co-crystal structures reveal that both compounds target a
      dynamic pocket near the catalytic centre of the auto-inhibited apo form of USP7,
      which differs from other USP deubiquitinases. Consistent with USP7 target
      engagement in cells, FT671 destabilizes USP7 substrates including MDM2, increases
      levels of p53, and results in the transcription of p53 target genes, induction of
      the tumour suppressor p21, and inhibition of tumour growth in mice.

PMID- 29045391
TI  - Network control principles predict neuron function in the Caenorhabditis elegans
      connectome.
AB  - Recent studies on the controllability of complex systems offer a powerful
      mathematical framework to systematically explore the structure-function
      relationship in biological, social, and technological networks. Despite
      theoretical advances, we lack direct experimental proof of the validity of these
      widely used control principles. Here we fill this gap by applying a control
      framework to the connectome of the nematode Caenorhabditis elegans, allowing us
      to predict the involvement of each C. elegans neuron in locomotor behaviours. We
      predict that control of the muscles or motor neurons requires 12 neuronal
      classes, which include neuronal groups previously implicated in locomotion by
      laser ablation, as well as one previously uncharacterized neuron, PDB. We
      validate this prediction experimentally, finding that the ablation of PDB leads
      to a significant loss of dorsoventral polarity in large body bends. Importantly,
      control principles also allow us to investigate the involvement of individual
      neurons within each neuronal class. For example, we predict that, within the
      class of DD motor neurons, only three (DD04, DD05, or DD06) should affect
      locomotion when ablated individually. This prediction is also confirmed; single
      cell ablations of DD04 or DD05 specifically affect posterior body movements,
      whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions
      of weak connections, missing connections, and rewired connections in the current
      connectome, indicating the potential applicability of this analytical framework
      to larger and less well-characterized connectomes.

PMID- 29045392
TI  - Inflammation: Memory beyond immunity.

PMID- 29045393
TI  - Molecular evolution: No escape from the tangled bank.

PMID- 29045394
TI  - Structure of phycobilisome from the red alga Griffithsia pacifica.
AB  - Life on Earth depends on photosynthesis for its conversion of solar energy to
      chemical energy. Photosynthetic organisms have developed a variety of light
      harvesting systems to capture sunlight. The largest light-harvesting complex is
      the phycobilisome (PBS), the main light-harvesting antenna in cyanobacteria and
      red algae. It is composed of phycobiliproteins and linker proteins but the
      assembly mechanisms and energy transfer pathways of the PBS are not well
      understood. Here we report the structure of a 16.8-megadalton PBS from a red alga
      at 3.5 A resolution obtained by single-particle cryo-electron microscopy. We
      modelled 862 protein subunits, including 4 linkers in the core, 16 rod-core
      linkers and 52 rod linkers, and located a total of 2,048 chromophores. This
      structure reveals the mechanisms underlying specific interactions between linkers
      and phycobiliproteins, and the formation of linker skeletons. These results
      provide a firm structural basis for our understanding of complex assembly and the
      mechanisms of energy transfer within the PBS.

PMID- 29045395
TI  - Single-molecule imaging reveals receptor-G protein interactions at cell surface
      hot spots.
AB  - G-protein-coupled receptors mediate the biological effects of many hormones and
      neurotransmitters and are important pharmacological targets. They transmit their
      signals to the cell interior by interacting with G proteins. However, it is
      unclear how receptors and G proteins meet, interact and couple. Here we analyse
      the concerted motion of G-protein-coupled receptors and G proteins on the plasma
      membrane and provide a quantitative model that reveals the key factors that
      underlie the high spatiotemporal complexity of their interactions. Using two
      colour, single-molecule imaging we visualize interactions between individual
      receptors and G proteins at the surface of living cells. Under basal conditions,
      receptors and G proteins form activity-dependent complexes that last for around
      one second. Agonists specifically regulate the kinetics of receptor-G protein
      interactions, mainly by increasing their association rate. We find hot spots on
      the plasma membrane, at least partially defined by the cytoskeleton and clathrin
      coated pits, in which receptors and G proteins are confined and preferentially
      couple. Imaging with the nanobody Nb37 suggests that signalling by G-protein
      coupled receptors occurs preferentially at these hot spots. These findings shed
      new light on the dynamic interactions that control G-protein-coupled receptor
      signalling.

PMID- 29045396
TI  - Indirect effects drive coevolution in mutualistic networks.
AB  - Ecological interactions have been acknowledged to play a key role in shaping
      biodiversity. Yet a major challenge for evolutionary biology is to understand the
      role of ecological interactions in shaping trait evolution when progressing from
      pairs of interacting species to multispecies interaction networks. Here we
      introduce an approach that integrates coevolutionary dynamics and network
      structure. Our results show that non-interacting species can be as important as
      directly interacting species in shaping coevolution within mutualistic
      assemblages. The contribution of indirect effects differs among types of
      mutualism. Indirect effects are more likely to predominate in nested, species
      rich networks formed by multiple-partner mutualisms, such as pollination or seed
      dispersal by animals, than in small and modular networks formed by intimate
      mutualisms, such as those between host plants and their protective ants.
      Coevolutionary pathways of indirect effects favour ongoing trait evolution by
      promoting slow but continuous reorganization of the adaptive landscape of
      mutualistic partners under changing environments. Our results show that
      coevolution can be a major process shaping species traits throughout ecological
      networks. These findings expand our understanding of how evolution driven by
      interactions occurs through the interplay of selection pressures moving along
      multiple direct and indirect pathways.

PMID- 29045397
TI  - Glucose feeds the TCA cycle via circulating lactate.
AB  - Mammalian tissues are fuelled by circulating nutrients, including glucose, amino
      acids, and various intermediary metabolites. Under aerobic conditions, glucose is
      generally assumed to be burned fully by tissues via the tricarboxylic acid cycle
      (TCA cycle) to carbon dioxide. Alternatively, glucose can be catabolized
      anaerobically via glycolysis to lactate, which is itself also a potential
      nutrient for tissues and tumours. The quantitative relevance of circulating
      lactate or other metabolic intermediates as fuels remains unclear. Here we
      systematically examine the fluxes of circulating metabolites in mice, and find
      that lactate can be a primary source of carbon for the TCA cycle and thus of
      energy. Intravenous infusions of 13C-labelled nutrients reveal that, on a molar
      basis, the circulatory turnover flux of lactate is the highest of all metabolites
      and exceeds that of glucose by 1.1-fold in fed mice and 2.5-fold in fasting mice;
      lactate is made primarily from glucose but also from other sources. In both fed
      and fasted mice, 13C-lactate extensively labels TCA cycle intermediates in all
      tissues. Quantitative analysis reveals that during the fasted state, the
      contribution of glucose to tissue TCA metabolism is primarily indirect (via
      circulating lactate) in all tissues except the brain. In genetically engineered
      lung and pancreatic cancer tumours in fasted mice, the contribution of
      circulating lactate to TCA cycle intermediates exceeds that of glucose, with
      glutamine making a larger contribution than lactate in pancreatic cancer. Thus,
      glycolysis and the TCA cycle are uncoupled at the level of lactate, which is a
      primary circulating TCA substrate in most tissues and tumours.

PMID- 29045399
TI  - Correction: Comparative transcriptomes of adenocarcinomas and squamous cell
      carcinomas reveal molecular similarities that span classical anatomic boundaries.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006938.].

PMID- 29045398
TI  - Nonlatching positive feedback enables robust bimodality by decoupling expression
      noise from the mean.
AB  - Fundamental to biological decision-making is the ability to generate bimodal
      expression patterns where 2 alternate expression states simultaneously exist.
      Here, we use a combination of single-cell analysis and mathematical modeling to
      examine the sources of bimodality in the transcriptional program controlling
      HIV's fate decision between active replication and viral latency. We find that
      the HIV transactivator of transcription (Tat) protein manipulates the intrinsic
      toggling of HIV's promoter, the long terminal repeat (LTR), to generate bimodal
      ON-OFF expression and that transcriptional positive feedback from Tat shifts and
      expands the regime of LTR bimodality. This result holds for both minimal
      synthetic viral circuits and full-length virus. Strikingly, computational
      analysis indicates that the Tat circuit's noncooperative "nonlatching" feedback
      architecture is optimized to slow the promoter's toggling and generate bimodality
      by stochastic extinction of Tat. In contrast to the standard Poisson model,
      theory and experiment show that nonlatching positive feedback substantially
      dampens the inverse noise-mean relationship to maintain stochastic bimodality
      despite increasing mean expression levels. Given the rapid evolution of HIV, the
      presence of a circuit optimized to robustly generate bimodal expression appears
      consistent with the hypothesis that HIV's decision between active replication and
      latency provides a viral fitness advantage. More broadly, the results suggest
      that positive-feedback circuits may have evolved not only for signal
      amplification but also for robustly generating bimodality by decoupling
      expression fluctuations (noise) from mean expression levels.

PMID- 29045400
TI  - Analysis of temporal transcription expression profiles reveal links between
      protein function and developmental stages of Drosophila melanogaster.
AB  - Accurate gene or protein function prediction is a key challenge in the post
      genome era. Most current methods perform well on molecular function prediction,
      but struggle to provide useful annotations relating to biological process
      functions due to the limited power of sequence-based features in that functional
      domain. In this work, we systematically evaluate the predictive power of temporal
      transcription expression profiles for protein function prediction in Drosophila
      melanogaster. Our results show significantly better performance on predicting
      protein function when transcription expression profile-based features are
      integrated with sequence-derived features, compared with the sequence-derived
      features alone. We also observe that the combination of expression-based and
      sequence-based features leads to further improvement of accuracy on predicting
      all three domains of gene function. Based on the optimal feature combinations, we
      then propose a novel multi-classifier-based function prediction method for
      Drosophila melanogaster proteins, FFPred-fly+. Interpreting our machine learning
      models also allows us to identify some of the underlying links between biological
      processes and developmental stages of Drosophila melanogaster.

PMID- 29045401
TI  - Genome-wide SNPs reveal the drivers of gene flow in an urban population of the
      Asian Tiger Mosquito, Aedes albopictus.
AB  - Aedes albopictus is a highly invasive disease vector with an expanding worldwide
      distribution. Genetic assays using low to medium resolution markers have found
      little evidence of spatial genetic structure even at broad geographic scales,
      suggesting frequent passive movement along human transportation networks. Here we
      analysed genetic structure of Aedes albopictus collected from 12 sample sites in
      Guangzhou, China, using thousands of genome-wide single nucleotide polymorphisms
      (SNPs). We found evidence for passive gene flow, with distance from shipping
      terminals being the strongest predictor of genetic distance among mosquitoes. As
      further evidence of passive dispersal, we found multiple pairs of full-siblings
      distributed between two sample sites 3.7 km apart. After accounting for
      geographical variability, we also found evidence for isolation by distance,
      previously undetectable in Ae. albopictus. These findings demonstrate how large
      SNP datasets and spatially-explicit hypothesis testing can be used to decipher
      processes at finer geographic scales than formerly possible. Our approach can be
      used to help predict new invasion pathways of Ae. albopictus and to refine
      strategies for vector control that involve the transformation or suppression of
      mosquito populations.

PMID- 29045402
TI  - Triadic male-infant-male interaction serves in bond maintenance in male Assamese
      macaques.
AB  - While the ultimate consequences of social bonds start to be better understood,
      the proximate behavioural mechanisms underlying the formation and maintenance of
      these close affiliative relationships have received less attention. We
      investigated the possible function of male-infant-male interactions (MIMIs) in
      male-male social bonding processes by analysing about 9000h of focal animal
      observations collected on two groups of wild Assamese macaques. In support of an
      agonistic buffering function of MIMIs, after engaging in a MIMI upon approach,
      subordinates stayed longer in close proximity of a dominant male. Overall, the
      frequency of MIMIs increased the stronger the affiliative relationship between
      two males, suggesting that MIMIs like grooming function in relationship
      maintenance. We did not find support for a role of MIMIs in bond formation as the
      frequency of MIMIs did not affect the time a male dyad spent in proximity in the
      consecutive year. Our results contribute to the general debate on behaviours
      influencing social dynamics in group living mammals.

PMID- 29045403
TI  - Mentalized affectivity: A new model and assessment of emotion regulation.
AB  - Here we introduce a new assessment of emotion regulation called the Mentalized
      Affectivity Scale (MAS). A large online adult sample (N = 2,840) completed the 60
      item MAS along with a battery of psychological measures. Results revealed a
      robust three-component structure underlying mentalized affectivity, which we
      labeled: Identifying emotions (the ability to identify emotions and to reflect on
      the factors that influence them); Processing emotions (the ability to modulate
      and distinguish complex emotions); and Expressing emotions (the tendency to
      express emotions outwardly or inwardly). Hierarchical modeling suggested that
      Processing emotions delineates from Identifying them, and Expressing emotions
      delineates from Processing them. We then showed how these components are
      associated with personality traits, well-being, trauma, and 18 different
      psychological disorders (including mood, neurological, and personality
      disorders). Notably, those with anxiety, mood, and personality disorders showed a
      profile of high Identifying and low Processing compared to controls. Further,
      results showed how mentalized affectivity scores varied across psychological
      treatment modalities and years spent in therapy. Taken together, the model of
      mentalized affectivity advances prior theory and research on emotion regulation
      and the MAS is a useful and reliable instrument that can be used in both clinical
      and non-clinical settings in psychology, psychiatry, and neuroscience.

PMID- 29045404
TI  - Transcriptomic responses of Biomphalaria pfeifferi to Schistosoma mansoni:
      Investigation of a neglected African snail that supports more S. mansoni
      transmission than any other snail species.
AB  - BACKGROUND: Biomphalaria pfeifferi is highly compatible with the widespread human
      infecting blood fluke Schistosoma mansoni and transmits more cases of this
      parasite to people than any other snail species. For these reasons, B. pfeifferi
      is the world's most important vector snail for S. mansoni, yet we know relatively
      little at the molecular level regarding the interactions between B. pfeifferi and
      S. mansoni from early-stage sporocyst transformation to the development of
      cercariae. METHODOLOGY/PRINCIPAL FINDINGS: We sought to capture a portrait of the
      response of B. pfeifferi to S. mansoni as it occurs in nature by undertaking
      Illumina dual RNA-Seq on uninfected control B. pfeifferi and three intramolluscan
      developmental stages (1- and 3-days post infection and patent, cercariae
      producing infections) using field-derived west Kenyan specimens. A high-quality,
      well-annotated de novo B. pfeifferi transcriptome was assembled from over a half
      billion non-S. mansoni paired-end reads. Reads associated with potential
      symbionts were noted. Some infected snails yielded fewer normalized S. mansoni
      reads and showed different patterns of transcriptional response than others, an
      indication that the ability of field-derived snails to support and respond to
      infection is variable. Alterations in transcripts associated with reproduction
      were noted, including for the oviposition-related hormone ovipostatin and enzymes
      involved in metabolism of bioactive amines like dopamine or serotonin. Shedding
      snails exhibited responses consistent with the need for tissue repair. Both
      generalized stress and immune factors immune factors (VIgLs, PGRPs, BGBPs,
      complement C1q-like, chitinases) exhibited complex transcriptional responses in
      this compatible host-parasite system. SIGNIFICANCE: This study provides for the
      first time a large sequence data set to help in interpreting the important vector
      role of the neglected snail B. pfeifferi in transmission of S. mansoni, including
      with an emphasis on more natural, field-derived specimens. We have identified B.
      pfeifferi targets particularly responsive during infection that enable further
      dissection of the functional role of these candidate molecules.

PMID- 29045406
TI  - MicroRNA profiling of human primary macrophages exposed to dengue virus
      identifies miRNA-3614-5p as antiviral and regulator of ADAR1 expression.
AB  - BACKGROUND: Due to the high burden of dengue disease worldwide, a better
      understanding of the interactions between dengue virus (DENV) and its human host
      cells is of the utmost importance. Although microRNAs modulate the outcome of
      several viral infections, their contribution to DENV replication is poorly
      understood. METHODS AND PRINCIPAL FINDINGS: We investigated the microRNA
      expression profile of primary human macrophages challenged with DENV and
      deciphered the contribution of microRNAs to infection. To this end, human primary
      macrophages were challenged with GFP-expressing DENV and sorted to differentiate
      between truly infected cells (DENV-positive) and DENV-exposed but non-infected
      cells (DENV-negative cells). The miRNAome was determined by small RNA-Seq
      analysis and the effect of differentially expressed microRNAs on DENV yield was
      examined. Five microRNAs were differentially expressed in human macrophages
      challenged with DENV. Of these, miR-3614-5p was found upregulated in DENV
      negative cells and its overexpression reduced DENV infectivity. The cellular
      targets of miR-3614-5p were identified by liquid chromatography/mass spectrometry
      and western blot. Adenosine deaminase acting on RNA 1 (ADAR1) was identified as
      one of the targets of miR-3614-5p and was shown to promote DENV infectivity at
      early time points post-infection. CONCLUSION/SIGNIFICANCE: Overall, miRNAs appear
      to play a limited role in DENV replication in primary human macrophages. The
      miRNAs that were found upregulated in DENV-infected cells did not control the
      production of infectious virus particles. On the other hand, miR-3614-5p, which
      was upregulated in DENV-negative macrophages, reduced DENV infectivity and
      regulated ADAR1 expression, a protein that facilitates viral replication.

PMID- 29045405
TI  - The study of trypanosome species circulating in domestic animals in two human
      African trypanosomiasis foci of Cote d'Ivoire identifies pigs and cattle as
      potential reservoirs of Trypanosoma brucei gambiense.
AB  - BACKGROUND: Important control efforts have led to a significant reduction of the
      prevalence of human African trypanosomiasis (HAT) in Cote d'Ivoire, but the
      disease is still present in several foci. The existence of an animal reservoir of
      Trypanosoma brucei gambiense may explain disease persistence in these foci where
      animal breeding is an important source of income but where the prevalence of
      animal African trypanosomiasis (AAT) is unknown. The aim of this study was to
      identify the trypanosome species circulating in domestic animals in both Bonon
      and Sinfra HAT endemic foci. METHODOLOGY/PRINCIPAL FINDINGS: 552 domestic animals
      (goats, pigs, cattle and sheep) were included. Blood samples were tested for
      trypanosomes by microscopic observation, species-specific PCR for T. brucei sl,
      T. congolense, T. vivax and subspecies-specific PCR for T. b. gambiense and T. b.
      gambiense immune trypanolysis (TL). Infection rates varied significantly between
      animal species and were by far the highest in pigs (30%). T. brucei s.l was the
      most prevalent trypanosome species (13.7%) followed by T. congolense. No T. b.
      gambiense was identified by PCR while high TL positivity rates were observed
      using T. b. gambiense specific variants (up to 27.6% for pigs in the Bonon
      focus). CONCLUSION: This study shows that domestic animals are highly infected by
      trypanosomes in the studied foci. This was particularly true for pigs, possibly
      due to a higher exposure of these animals to tsetse flies. Whereas T. brucei s.l.
      was the most prevalent species, discordant results were obtained between PCR and
      TL regarding T. b. gambiense identification. It is therefore crucial to develop
      better tools to study the epidemiological role of potential animal reservoir for
      T. b. gambiense. Our study illustrates the importance of "one health" approaches
      to reach HAT elimination and contribute to AAT control in the studied foci.

PMID- 29045407
TI  - Bayesian refinement of protein structures and ensembles against SAXS data using
      molecular dynamics.
AB  - Small-angle X-ray scattering is an increasingly popular technique used to detect
      protein structures and ensembles in solution. However, the refinement of
      structures and ensembles against SAXS data is often ambiguous due to the low
      information content of SAXS data, unknown systematic errors, and unknown
      scattering contributions from the solvent. We offer a solution to such problems
      by combining Bayesian inference with all-atom molecular dynamics simulations and
      explicit-solvent SAXS calculations. The Bayesian formulation correctly weights
      the SAXS data versus prior physical knowledge, it quantifies the precision or
      ambiguity of fitted structures and ensembles, and it accounts for unknown
      systematic errors due to poor buffer matching. The method further provides a
      probabilistic criterion for identifying the number of states required to explain
      the SAXS data. The method is validated by refining ensembles of a periplasmic
      binding protein against calculated SAXS curves. Subsequently, we derive the
      solution ensembles of the eukaryotic chaperone heat shock protein 90 (Hsp90)
      against experimental SAXS data. We find that the SAXS data of the apo state of
      Hsp90 is compatible with a single wide-open conformation, whereas the SAXS data
      of Hsp90 bound to ATP or to an ATP-analogue strongly suggest heterogenous
      ensembles of a closed and a wide-open state.

PMID- 29045408
TI  - Older adults' acceptance of a robot for partner dance-based exercise.
AB  - Partner dance has been shown to be beneficial for the health of older adults.
      Robots could potentially facilitate healthy aging by engaging older adults in
      partner dance-based exercise. However, partner dance involves physical contact
      between the dancers, and older adults would need to be accepting of partner
      dancing with a robot. Using methods from the technology acceptance literature, we
      conducted a study with 16 healthy older adults to investigate their acceptance of
      robots for partner dance-based exercise. Participants successfully led a human
      scale wheeled robot with arms (i.e., a mobile manipulator) in a simple, which we
      refer to as the Partnered Stepping Task (PST). Participants led the robot by
      maintaining physical contact and applying forces to the robot's end effectors.
      According to questionnaires, participants were generally accepting of the robot
      for partner dance-based exercise, tending to perceive it as useful, easy to use,
      and enjoyable. Participants tended to perceive the robot as easier to use after
      performing the PST with it. Through a qualitative data analysis of structured
      interview data, we also identified facilitators and barriers to acceptance of
      robots for partner dance-based exercise. Throughout the study, our robot used
      admittance control to successfully dance with older adults, demonstrating the
      feasibility of this method. Overall, our results suggest that robots could
      successfully engage older adults in partner dance-based exercise.

PMID- 29045409
TI  - Psychometric validation of the Italian Rehabilitation Complexity Scale-Extended
      version 13.
AB  - In Italy, at present, a well-known problem is inhomogeneous provision of
      rehabilitative services, as stressed by MoH, requiring appropriate criteria and
      parameters to plan rehabilitation actions. According to the Italian National
      Rehabilitation Plan, Comorbidity, Disability and Clinical Complexity should be
      assessed to define the patient's real needs. However, to date, clinical
      complexity is still difficult to measure with shared and validated tools. The
      study aims to psychometrically validate the Italian Rehabilitation Complexity
      Scale-Extended v13 (RCS-E v13), in order to meet the guidelines requirements. An
      observational multicentre prospective cohort study, involving 8 intensive
      rehabilitation facilities of the Emilia-Romagna Region and 1712 in-patients, [823
      male (48%) and 889 female (52%), mean age 68.34 years (95% CI 67.69-69.00 years)]
      showing neurological, orthopaedic and cardiological problems, was carried out.
      The construct and concurrent validity of the RCS-E v13 was confirmed through its
      correlation to Barthel Index (disability) and Cumulative Illness Rating Scale
      (comorbidity) and appropriate admission criteria (not yet published),
      respectively. Furthermore, the factor analysis indicated two different components
      ("Basic Care or Risk-Equipment" and "Medical-Nursing Needs and Therapy
      Disciplines") of the RCS-E v13. In conclusion, the Italian RCS-E v13 appears to
      be a useful tool to assess clinical complexity in the Italian rehab scenario case
      mix and its psychometric validation may have an important clinical rehabilitation
      impact allowing the assessment of the rehabilitation needs considering all three
      dimensions (disability, comorbidity and clinical complexity) as required by the
      Guidelines and the inhomogeneity could be reduced.

PMID- 29045411
TI  - Mating-induced sexual inhibition in the jumping spider Servaea incana (Araneae:
      Salticidae): A fast-acting and long-lasting effect.
AB  - Mating-induced sexual inhibition has been studied extensively as an important
      facet of many insect mating systems but remains little understood in spiders.
      Once mated, females of many spider species become unreceptive and aggressive
      toward males, but the speed of onset and persistence of this effect are not
      known. Addressing this gap, the present study considers (1) mating tendency of
      virgins, latency to remating, and lifetime mating frequency and (2) how quickly
      sexual inhibition is expressed after the first mating in female Servaea incana
      jumping spiders. Encounters between males and females took place in two contexts
      that simulated locations where mating occurs in nature: in the light away from
      nests ('in the open') and in low light within the shelter of silken retreats ('at
      a retreat'). Virgin females exhibited high receptivity levels in both contexts
      but sexual inhibition was induced immediately after their first copulation. The
      most common tendency was for just one mating in a lifetime, and few females mated
      more than twice. Context also had an effect on female mating tendency, as virgin
      females in the open rejected more males before accepting their first mate than
      did virgin females in retreats. Considering only those females that did remate,
      females in the open tended to reject fewer males before remating. Given low
      levels of female remating, virgin females appear to be at a premium for male
      reproductive fitness in S. incana jumping spiders and this is a likely
      explanation for protandry found in nature.

PMID- 29045410
TI  - Patterns and rates of viral evolution in HIV-1 subtype B infected females and
      males.
AB  - Biological sex differences affect the course of HIV infection, with untreated
      women having lower viral loads compared to their male counterparts but, for a
      given viral load, women have a higher rate of progression to AIDS. However, the
      vast majority of data on viral evolution, a process that is clearly impacted by
      host immunity and could be impacted by sex differences, has been derived from
      men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution
      taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study
      (WIHS) participants who had not received combination antiretroviral therapy
      (ART). This was compared to similar data previously collected from men, with both
      groups infected with HIV-1 subtype B. Early virus populations in men and women
      were generally homogenous with no differences in diversity between sexes. No
      differences in ensuing nucleotide substitution rates were found between the
      female and male cohorts studied herein. As previously reported for men, time to
      peak diversity in env-gp120 in women was positively associated with time to CD4+
      cell count below 200 (P = 0.017), and the number of predicted N-linked
      glycosylation sites generally increased over time, followed by a plateau or
      decline, with the majority of changes localized to the V1-V2 region. These
      findings strongly suggest that the sex differences in HIV-1 disease progression
      attributed to immune system composition and sensitivities are not revealed by,
      nor do they impact, global patterns of viral evolution, the latter of which
      proceeds similarly in women and men.

PMID- 29045413
TI  - Contribution of proton leak to oxygen consumption in skeletal muscle during
      intense exercise is very low despite large contribution at rest.
AB  - A computer model was used to simulate the dependence of protonmotive force
      (Deltap), proton leak and phenomenological (involving proton leak) ATP/O2 ratio
      on work intensity in skeletal muscle. Deltap, NADH and proton leak decreased with
      work intensity. The contribution of proton leak to oxygen consumption ([Formula:
      see text]) decreased from about 60% at rest to about 3 and 1% at moderate and
      heavy/severe exercise, respectively, while the ATP/O2 ratio increased from 2.1 to
      5.5 and 5.7. A two-fold increase in proton leak activity or its decrease to zero
      decreased/increased the ATP/O2 ratio by only about 3 and 1% during moderate and
      heavy/severe exercise, respectively. The low contribution of proton leak to
      [Formula: see text] in intensively working skeletal muscle was mostly caused by a
      huge increase in ATP usage intensity during rest-to-work transition, while
      OXPHOS, and thus oxidative ATP supply and [Formula: see text] related to it, was
      mostly stimulated by high each-step activation (ESA) of OXPHOS complexes. The
      contribution of proton leak to [Formula: see text] and ATP/O2 ratio in isolated
      mitochondria should not be directly extrapolated to working muscle, as
      mitochondria lack ESA, at least in the absence of Ca2+, and therefore [Formula:
      see text] cannot be elevated as much as in intact muscle.

PMID- 29045412
TI  - Self-domestication in Homo sapiens: Insights from comparative genomics.
AB  - This study identifies and analyzes statistically significant overlaps between
      selective sweep screens in anatomically modern humans and several domesticated
      species. The results obtained suggest that (paleo-)genomic data can be exploited
      to complement the fossil record and support the idea of self-domestication in
      Homo sapiens, a process that likely intensified as our species populated its
      niche. Our analysis lends support to attempts to capture the "domestication
      syndrome" in terms of alterations to certain signaling pathways and cell
      lineages, such as the neural crest.

PMID- 29045414
TI  - Influence of Poly(vinylpyrrolidone) concentration on properties of silver
      nanoparticles manufactured by modified thermal treatment method.
AB  - Very narrow and pure silver nanoparticles were synthesized by modified thermal
      treatment method via oxygen and nitrogen flow in succession. The structural and
      optical properties of the calcined silver nanoparticles at 600 degrees C with
      diverse Poly(vinylpyrrolidone) concentrations varied from 2% to 4% were studied
      by means of different techniques. Fourier transform infrared spectroscopy was
      used to monitor the production of pure Ag nanoparticles at a given
      Poly(vinylpyrrolidone) concentration. The X-ray powder diffraction spectra are
      evidence for the transformation of the amorphous sample at 30 degrees C to the
      cubic crystalline nanostructures at the calcination temperatures for all
      Poly(vinylpyrrolidone) concentrations. The transmission electron microscopy
      images showed the creation of spherical silver nanoparticles with the average
      particle size decreased by increasing Poly(vinylpyrrolidone) concentrations from
      4.61 nm at 2% to 2.49 nm at 4% Poly(vinylpyrrolidone). The optical properties
      were investigated by means of UV-vis absorption spectrophotometer, which showed
      an increase in the conduction band of Ag nanoparticles with increasing
      Poly(vinylpyrrolidone) concentrations from 2.83 eV at 2% Poly(vinylpyrrolidone)
      to 2.94 eV at 4% Poly(vinylpyrrolidone) due to decreasing particle size. This was
      due to less attraction between conduction electrons and metal ions for smaller
      particle size corresponding to fewer atoms that made up the metal nanoparticles.

PMID- 29045415
TI  - Isolation, identification and phenotypic and molecular characterization of
      pathogenic Vibrio vulnificus isolated from Litopenaeus vannamei.
AB  - The morphology and the drug sensitivity of the strain GYX2014-1 isolated from the
      hepatic pancreatic tissue of moribund Litopenaeus vannamei were evaluated by
      conventional culture characteristics, physical and chemical characteristics, and
      molecular biology methods. Detection of extracellulase and hemolysin activity
      shows that the isolated GYX2014-1 has protease, lipase, gelatinase activity, but
      none of amylase, or lecithinase activity. The 16S rRNA gene (GenBank accession
      number: KT781675) was analyzed, and a phylogenetic tree analysis showed that the
      isolated pathogen was most closely related to V. vulnificus (GenBank accession
      number: NR 118570)-a match of more than 99%. The phenotypic traits and molecular
      biology of isolated bacteria, determined their identity as Vibrio vulnificus (V.
      vulnificus). In addition, artificially infected L. vannamei with Vibrio
      vulnificus appeared with the same disease symptoms as those of naturally infected
      shrimp. Drug sensitivity tests showed that V. vulnificus is highly sensitive to
      fosfomycin, cefradine and sinomin, and was resistant to penicillin, amikacin and
      kanamycin. This experiment is the first to separate V. vulnificus from L.
      vannamei, and the findings of this study can be used as a reference for disease
      control and health management.

PMID- 29045416
TI  - Neonatal immune response to rhinovirus A16 has diminished dendritic cell function
      and increased B cell activation.
AB  - BACKGROUND: Rhinovirus infections during infancy account for the majority of
      respiratory illness health care utilization and are an associated risk factor for
      subsequent development of allergic asthma. Neonatal type I interferon production
      is diminished compared to adults after stimulation with TLR agonists. However,
      broad profiling of immune cell responses to infectious rhinovirus has not been
      undertaken and we hypothesized that additional immune differences can be
      identified in neonates. In this study, we undertook a comparative analysis of
      neonatal and adult blood immune cell responses after in vitro incubation with
      infectious RV-A16 for 6 and 24 hours. METHODS: Intracellular proinflammatory and
      type I interferon cytokines along with expression of surface co-stimulatory and
      maturation markers were measured using multi-parameter flow cytometry. RESULTS:
      Both circulating myeloid dendritic cell (mDC) and plasmacytoid dendritic cell
      (pDC) frequency were lower in cord blood. Qualitative and quantitative
      plasmacytoid dendritic cell IFN-alpha + TNF- alpha responses to rhinovirus were
      significantly lower in cord pDCs. In cord blood samples, the majority of
      responsive pDCs were single-positive TNF-alpha producing cells, whereas in adult
      samples rhinovirus increased double-positive TNF-alpha+IFN-alpha+ pDCs.
      Rhinovirus upregulated activation and maturation markers on monocytes, mDCs,
      pDCs, and B cells, but CD40+CD86+ monocytes, mDCs, and pDCs cells were
      significantly higher in adult samples compared to cord samples. Surprisingly,
      rhinovirus increased CD40+CD86+ B cells to a significantly greater extent in cord
      samples compared to adults. CONCLUSIONS: These findings define a number of cell
      specific differences in neonatal responses to rhinovirus. This differential age
      related immune response to RV may have implications for the immune correlates of
      protection to viral respiratory illness burden and determination of potential
      biomarkers for asthma risk.

PMID- 29045417
TI  - Effects of food store quality on hibernation performance in common hamsters.
AB  - Hibernating animals can adjust torpor expression according to available energy
      reserves. Besides the quantity, the quality of energy reserves could play an
      important role for overwintering strategies. Common hamsters are food-storing
      hibernators and show high individual variation in hibernation performance, which
      might be related to the quality of food hoards in the hibernacula. In this study,
      we tested the effects of food stores high in fat content, particularly
      polyunsaturated fatty acids (PUFAs), on hibernation patterns under laboratory
      conditions. Control animals received standard rodent pellets only, while in the
      other group pellets were supplemented with sunflower seeds. We recorded body
      temperature during winter using subcutaneously implanted data loggers, documented
      total food consumption during winter, and analysed PUFA proportions in white
      adipose tissue (WAT) before and after the winter period. About half of the
      individuals in both groups hibernated and torpor expression did not differ
      between these animals. Among the high-fat group, however, individuals with high
      sunflower seeds intake strongly reduced the time spent in deep torpor. PUFA
      proportions in WAT decreased during winter in both groups and this decline was
      positively related to the time an individual spent in deep torpor. Sunflower
      seeds intake dampened the PUFA decline resulting in higher PUFA levels in animals
      of the high-fat group after winter. In conclusion, our results showed that common
      hamsters adjusted torpor expression and food intake in relation to the total
      energy of food reserves, underlining the importance of food hoard quality on
      hibernation performance.

PMID- 29045418
TI  - More than 75 percent decline over 27 years in total flying insect biomass in
      protected areas.
AB  - Global declines in insects have sparked wide interest among scientists,
      politicians, and the general public. Loss of insect diversity and abundance is
      expected to provoke cascading effects on food webs and to jeopardize ecosystem
      services. Our understanding of the extent and underlying causes of this decline
      is based on the abundance of single species or taxonomic groups only, rather than
      changes in insect biomass which is more relevant for ecological functioning.
      Here, we used a standardized protocol to measure total insect biomass using
      Malaise traps, deployed over 27 years in 63 nature protection areas in Germany
      (96 unique location-year combinations) to infer on the status and trend of local
      entomofauna. Our analysis estimates a seasonal decline of 76%, and mid-summer
      decline of 82% in flying insect biomass over the 27 years of study. We show that
      this decline is apparent regardless of habitat type, while changes in weather,
      land use, and habitat characteristics cannot explain this overall decline. This
      yet unrecognized loss of insect biomass must be taken into account in evaluating
      declines in abundance of species depending on insects as a food source, and
      ecosystem functioning in the European landscape.

PMID- 29045419
TI  - The cost of mapping trachoma: Data from the Global Trachoma Mapping Project.
AB  - BACKGROUND: The Global Trachoma Mapping Project (GTMP) was implemented with the
      aim of completing the baseline map of trachoma globally. Over 2.6 million people
      were examined in 1,546 districts across 29 countries between December 2012 and
      January 2016. The aim of the analysis was to estimate the unit cost and to
      identify the key cost drivers of trachoma prevalence surveys conducted as part of
      GTMP. METHODOLOGY AND PRINCIPAL FINDINGS: In-country and global support costs
      were obtained using GTMP financial records. In-country expenditure was analysed
      for 1,164 districts across 17 countries. The mean survey cost was $13,113 per
      district [median: $11,675; IQR = $8,365-$14,618], $17,566 per evaluation unit
      [median: $15,839; IQR = $10,773-$19,915], $692 per cluster [median: $625; IQR =
      $452-$847] and $6.0 per person screened [median: $4.9; IQR = $3.7-$7.9]. Survey
      unit costs varied substantially across settings, and were driven by parameters
      such as geographic location, demographic characteristics, seasonal effects, and
      local operational constraints. Analysis by activities showed that fieldwork
      constituted the largest share of in-country survey costs (74%), followed by
      training of survey teams (11%). The main drivers of in-country survey costs were
      personnel (49%) and transportation (44%). Global support expenditure for all
      surveyed districts amounted to $5.1m, which included grant management,
      epidemiological support, and data stewardship. CONCLUSION: This study provides
      the most extensive analysis of the cost of conducting trachoma prevalence surveys
      to date. The findings can aid planning and budgeting for future trachoma surveys
      required to measure the impact of trachoma elimination activities. Furthermore,
      the results of this study can also be used as a cost basis for other disease
      mapping programmes, where disease or context-specific survey cost data are not
      available.

PMID- 29045420
TI  - Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and
      enhances auricular cartilage regeneration.
AB  - Why regeneration does not occur in mammals remains elusive. In lower vertebrates,
      epimorphic regeneration of the limb is directed by the wound epidermis, which
      controls blastema formation to promote regrowth of the appendage. Herein, we
      report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1
      (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5),
      after full thickness ear punch in mice prolongs keratinocyte activation within
      the wound epidermis and promotes regeneration of auricular cartilage.
      Histological analysis showed the ASK1 KO ears displayed enhanced protein markers
      associated with blastema formation, hole closure and regeneration of auricular
      cartilage. At seven days after punch, the wound epidermis morphology was markedly
      different in the KO, showing a thickened stratum corneum with rounded cell
      morphology and a reduction of both the granular cell layer and decreased
      expression of filament aggregating protein. In addition, cytokeratin 6 was
      expressed in the stratum spinosum and granulosum. Topical application of
      inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated
      mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase
      (SP600125) also resulted in enhanced regeneration; whereas inhibition of the
      other downstream target, the p38 alpha/beta isoforms, (SB203580) had no effect.
      The results of this investigation indicate ASK1 inhibition prolongs keratinocyte
      and blastemal cell activation leading to ear regeneration.

PMID- 29045421
TI  - Enlarged Virchow Robin spaces associate with cognitive decline in multiple
      sclerosis.
AB  - The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain
      disorders, especially in multiple sclerosis (MS), is still undefined. We analysed
      enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI
      sequence and investigated their association with inflammation or brain atrophy,
      and to clinical or physical disability. Forty-three MS patients (21 clinically
      isolated syndrome suggestive of MS [CIS], 15 RRMS, 7 progressive [PMS]) and 10
      healthy controls (HC) were studied. 3DT1, 3DFLAIR and 2DPSIR images were obtained
      with a 3T MRI scanner. eVRS number and volume were calculated by manual
      segmentation (ITK-SNAP). Freesurfer was used to assess brain parenchymal fraction
      (BPF). All patients underwent clinical (EDSS) and cognitive (Rao's BRB and DKEFS)
      evaluation. eVRS number and volume resulted significantly higher on 2D-PSIR
      compared to both 3D-T1 (p<0.001) and 3D-FLAIR (p<0.001) and were significantly
      increased in CIS compared to HC (p<0.05), in PMS and RRMS compared to CIS
      (p<0.001) and in male versus female patients (p<0.05). eVRS volume increased
      significantly with disease duration (r = 0.6) but did not correlate with EDSS.
      eVRS significantly correlated with SPARTd (r = -0.47) and DKEFSfs (r = -0.46),
      especially when RRMS and PMS were merged in a single group (r = 0.89, p = 0.002
      and r = 0.66, p = 0.009 respectively), while no correlation was found with BPF (r
      = 0.3), gadolinium-enhancing lesions (r = 0.2) and WMT2 lesion volume (r = 0.2).
      2DPSIR allowed the detection of an impressive higher number of eVRS compared to
      3DT1 and 3DFLAIR. eVRS associate with SPARTd and DKEFSfs failure in relapse-onset
      MS, suggesting they may contribute to cognitive decline in MS.

PMID- 29045422
TI  - Cluster analysis identifies three urodynamic patterns in patients with orthotopic
      neobladder reconstruction.
AB  - PURPOSE: To classify patients with orthotopic neobladder based on urodynamic
      parameters using cluster analysis and to characterize the voiding function of
      each group. MATERIALS AND METHODS: From January 2012 to November 2015, 142
      patients with bladder cancer underwent radical cystectomy and Studer neobladder
      reconstruction at our institute. Of the 142 patients, 103 with complete
      urodynamic data and information on urinary functional outcomes were included in
      this study. K-means clustering was performed with urodynamic parameters which
      included maximal cystometric capacity, residual volume, maximal flow rate,
      compliance, and detrusor pressure at maximum flow rate. Three groups emerged by
      cluster analysis. Urodynamic parameters and urinary function outcomes were
      compared between three groups. RESULTS: Group 1 (n = 44) had ideal urodynamic
      parameters with a mean maximal bladder capacity of 513.3 ml and mean residual
      urine volume of 33.1 ml. Group 2 (n = 42) was characterized by small bladder
      capacity with low compliance. Patients in group 2 had higher rates of daytime
      incontinence and nighttime incontinence than patients in group 1. Group 3 (n =
      17) was characterized by large residual urine volume with high compliance. When
      we examined gender differences in urodynamics and functional outcomes, residual
      urine volume and the rate of daytime incontinence were only marginally
      significant. However, females were significantly more likely to belong to group 2
      or 3 (P = 0.003). In multivariate analysis to identify factors associated with
      group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017) and
      male gender (OR 7.57, P = 0.003) were identified as significant factors.
      CONCLUSIONS: While patients with ileal neobladder present with various voiding
      symptoms, three urodynamic patterns were identified by cluster analysis.
      Approximately half of patients had ideal urodynamic parameters. The other two
      groups were characterized by large residual urine and small capacity bladder with
      low compliance. Young age and male gender appear to have a favorable impact on
      urodynamic and voiding outcomes in patients undergoing orthotopic neobladder
      reconstruction.

PMID- 29045424
TI  - Cats and owners interact more with each other after a longer duration of
      separation.
AB  - Little is known about the cat's (Felis silvestris catus) need for human contact,
      although it is generally believed that cats are more independent pets than e.g.
      dogs. In this study, we investigated the effect of time left alone at home on cat
      behaviour (e.g. social and distress-related) before, during and after separation
      from their owner. Fourteen privately owned cats (single-housed) were each
      subjected to two treatments: the cat was left alone in their home environment for
      30 min (T0.5) and for 4 h (T4). There were no differences between treatments in
      the behaviour of the cat (or owner) before owner departure, nor during the first
      5 min of separation. During separation, cats were lying down resting
      proportionally less (T = 22.5, P = 0.02) in T0.5 (0.27+/-0.1 (mean+/-SE))
      compared to in T4 (0.58+/-0.08), probably due to a similar duration of higher
      activity early in the separation phase in both treatments. Comparisons of the
      time interval (min 20-25) in both treatments indicated no differences across
      treatments, which supports such an explanation. Towards the end of the separation
      phase (the last two 5-min intervals of separation in both treatments), no
      differences were observed in the cats' behaviour, indicating that cats were
      unaffected by separation length. At reunion however, cats purred more (T = 10.5,
      P = 0.03) and stretched their body more (T = 17, P = 0.04) after a longer
      duration of separation (T4:0.05+/-0.02; 0.03+/-0.01; T0.5: 0.01+/-0.007; 0.008+/
      0.003). Also, owners initiated more verbal contact (T = 33.5, P = 0.04) after 4 h
      (0.18+/-0.05) compared to after 30 min (0.12+/-0.03). There was no evidence of
      any correlations between the level of purring or body stretching by the cat and
      verbal contact by the owner implying that the behavioural expressions seen in the
      cats are independent of the owner's behaviour. Hence, it seemed as cats coped
      well with being left alone, but they were affected by the time they were left
      alone, since they expressed differences in behaviour when the owner returned
      home. The increased level of social contact initiated by the cats after a longer
      duration of separation indicates a rebound of contact-seeking behaviour, implying
      that the owner is an important part of the cat's social environment.

PMID- 29045423
TI  - Candidemia in non-ICU surgical wards: Comparison with medical wards.
AB  - Candidemia acquired outside critical care or hematological areas has received
      much attention in recent years; however, data on candidemia in surgical
      departments are very scarce. Our objectives were to describe episodes of
      candidemia diagnosed in surgical wards and to compare them with episodes
      occurring in medical wards. We performed a post hoc analysis of a prospective,
      multicenter study implemented in Spain during 2010-2011 (CANDIPOP project). Of
      the 752 episodes of candidemia, 369 (49.1%) occurred in patients admitted to
      surgical wards (165, 21.9%) or medical wards (204, 27.2%). Clinical
      characteristics associated with surgical patients were solid tumor as underlying
      disease, recent surgery, indwelling CVC, and parenteral nutrition. Candidemia was
      more commonly related to a CVC in the surgical than in the medical wards. The CVC
      was removed more frequently and early management was more appropriate within 48
      hours of blood sampling in the surgical patients. Overall, 30-day mortality in
      the surgical departments was significantly lower than in medical wards (37.7% vs.
      15.8%, p<0.001). Multivariate analysis revealed admission to a surgical ward and
      appropriate early management of candidemia as factors independently associated
      with a better outcome. We found that approximately 50% of episodes of candidemia
      occurred in non-hematological patients outside the ICU and that clinical outcome
      was better in patients admitted to surgical wards than in those hospitalized in
      medical wards. These findings can be explained by the lower severity of
      underlying disease, prompt administration of antifungal therapy, and central
      venous catheter removal.

PMID- 29045425
TI  - Comorbidities and health-related quality of life in Koreans with knee
      osteoarthritis: Data from the Korean National Health and Nutrition Examination
      Survey (KNHANES).
AB  - OBJECTIVES: This study aimed to evaluate the association of knee osteoarthritis
      (OA) with comorbidities and health-related quality of life (HRQOL). METHODS: A
      total of 8,907 (weighted n = 13,687,058) participants aged >=50 years who had
      undergone knee radiography were selected from the 2010-2012 Korea National Health
      and Nutrition Examination Survey. OA was classified into four subgroups based on
      the presence or absence of pain and radiographic OA (ROA): non-OA (Pain-/ROA-),
      pain only (Pain+/ROA-), ROA only (Pain-/ROA+), and painful ROA (Pain+/ROA+). ROA
      was defined as Kellgren-Lawrence grade >= 2. HRQOL measurements including EuroQOL
      visual analogue scale (EQ-VAS) scores and the five dimensions and summary index
      of the EuroQOL-5 dimension (EQ-5D index) were also analyzed. Multivariable
      logistic regression and linear regression analyses were performed. RESULTS: After
      adjustment for socioeconomic and lifestyle characteristics, cardiovascular
      disease, malignancy, and other comorbidities were not significantly associated
      with OA. Pain only and painful ROA were each significantly associated with
      limitations in physical activity (odds ratio (OR) 2.66, 95% CI 2.07-3.44, p <
      0.001 and OR 2.83, 95% CI 2.25-3.58, p < 0.001, respectively), lower EQ-VAS (beta
      coefficient = -10.95, p < 0.001 and beta-coefficient = -9.75, p < 0.001,
      respectively), and EQ-5D index (beta-coefficient = -0.10, p < 0.001 and beta
      coefficient = -0.13, p < 0.001) compared with the non-OA group, whereas ROA only
      was not associated with limitations in physical activity or lower HRQOL score.
      CONCLUSIONS: Comorbidities were not significantly associated with knee OA after
      adjustment. Knee OA was associated with physical activity and HRQOL. Painful knee
      OA, with or without ROA, was more strongly associated with decreased physical
      activity and lower quality of life than ROA without pain.

PMID- 29045426
TI  - Dogs' recognition of human selfish and generous attitudes requires little but
      critical experience with people.
AB  - There is some dispute regarding the role of experience in the development of
      dogs' socio-cognitive abilities in their interaction with people. We sought to
      provide new evidence to this debate by comparing dogs with contrasting levels of
      experience with humans, in a task involving the discrimination of human generous
      and selfish attitudes. To this end, we compared the performance of adult family
      dogs against that of adult shelter dogs and puppies living in people's homes. In
      training trials, the generous experimenter (G) signaled the bowl with food and
      allowed the dog to eat, whereas the selfish experimenter (S) also signaled the
      baited bowl, but she/he ate the food before the dog could have access to it.
      Then, subjects were allowed to freely choose between G and S in the choice test.
      The main finding was that adult subjects (both family and shelter dogs) developed
      a preference for G over S, but puppies did not. We conclude that the quality
      and/or quantity of everyday-contact with people did not affect the discrimination
      of human attitudes in the present protocol, but the amount of experience with
      people (in years) did matter. Finally, we discuss the relative role of
      domestication and ontogeny in the development of dogs' socio-cognitive abilities.

PMID- 29045427
TI  - More or less-On the influence of labelling strategies to infer cell population
      dynamics.
AB  - The adoptive transfer of labelled cell populations has been an essential tool to
      determine and quantify cellular dynamics. The experimental methods to label and
      track cells over time range from fluorescent dyes over congenic markers towards
      single-cell labelling techniques, such as genetic barcodes. While these methods
      have been widely used to quantify cell differentiation and division dynamics, the
      extent to which the applied labelling strategy actually affects the
      quantification of the dynamics has not been determined so far. This is especially
      important in situations where measurements can only be obtained at a single time
      point, as e.g. due to organ harvest. To this end, we studied the appropriateness
      of various labelling strategies as characterised by the number of different
      labels and the initial number of cells per label to quantify cellular dynamics.
      We simulated adoptive transfer experiments in systems of various complexity that
      assumed either homoeostatic cellular turnover or cell expansion dynamics
      involving various steps of cell differentiation and proliferation. Re-sampling
      cells at a single time point, we determined the ability of different labelling
      strategies to recover the underlying kinetics. Our results indicate that cell
      transition and expansion rates are differently affected by experimental
      shortcomings, such as loss of cells during transfer or sampling, dependent on the
      labelling strategy used. Furthermore, uniformly distributed labels in the
      transferred population generally lead to more robust and less biased results than
      non-equal label sizes. In addition, our analysis indicates that certain labelling
      approaches incorporate a systematic bias for the identification of complex cell
      expansion dynamics.

PMID- 29045428
TI  - The role of PKA in the translational response to heat stress in Saccharomyces
      cerevisiae.
AB  - Cellular responses to stress stem from a variety of different mechanisms,
      including translation arrest and relocation of the translationally repressed
      mRNAs to ribonucleoprotein particles like stress granules (SGs) and processing
      bodies (PBs). Here, we examine the role of PKA in the S. cerevisiae heat shock
      response. Under mild heat stress Tpk3 aggregates and promotes aggregation of
      eIF4G, Pab1 and eIF4E, whereas severe heat stress leads to the formation of PBs
      and SGs that contain both Tpk2 and Tpk3 and a larger 48S translation initiation
      complex. Deletion of TPK2 or TPK3 impacts upon the translational response to heat
      stress of several mRNAs including CYC1, HSP42, HSP30 and ENO2. TPK2 deletion
      leads to a robust translational arrest, an increase in SGs/PBs aggregation and
      translational hypersensitivity to heat stress, whereas TPK3 deletion represses
      SGs/PBs formation, translational arrest and response for the analyzed mRNAs.
      Therefore, this work provides evidence indicating that Tpk2 and Tpk3 have
      opposing roles in translational adaptation during heat stress, and highlight how
      the same signaling pathway can be regulated to generate strikingly distinct
      physiological outputs.

PMID- 29045429
TI  - Preclinical antivenom-efficacy testing reveals potentially disturbing
      deficiencies of snakebite treatment capability in East Africa.
AB  - BACKGROUND: Antivenom is the treatment of choice for snakebite, which annually
      kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately
      100,000 survivors with permanent physical disabilities that exert a considerable
      socioeconomic burden. Over the past two decades, the high costs of the most
      polyspecifically-effective antivenoms have sequentially reduced demand,
      commercial manufacturing incentives and production volumes that have combined to
      create a continent-wide vacuum of effective snakebite therapy. This was quickly
      filled with new, less expensive antivenoms, many of which are of untested
      efficacy. Some of these successfully marketed antivenoms for Africa are
      inappropriately manufactured with venoms from non-African snakes and are
      dangerously ineffective. The uncertain efficacy of available antivenoms
      exacerbates the complexity of designing intervention measures to reduce the
      burden of snakebite in sub-Saharan Africa. The objective of this study was to
      preclinically determine the ability of antivenoms available in Kenya to
      neutralise the lethal effects of venoms from the most medically important snakes
      in East Africa. METHODS: We collected venom samples from the most medically
      important snakes in East Africa and determined their toxicity in a mouse model.
      Using a 'gold standard' comparison protocol, we preclinically tested the
      comparative venom-neutralising efficacy of four antivenoms available in Kenya
      with two antivenoms of clinically-proven efficacy. To explain the variant
      efficacies of these antivenoms we tested the IgG-venom binding characteristics of
      each antivenom using in vitro IgG titre, avidity and venom-protein specificity
      assays. We also measured the IgG concentration of each antivenom. FINDINGS: None
      of the six antivenoms are preclinically effective, at the doses tested, against
      all of the most medically important snakes of the region. The very limited snake
      polyspecific efficacy of two locally available antivenoms is of concern. In vitro
      assays of the abilities of 'test' antivenom IgGs to bind venom proteins were not
      substantially different from that of the 'gold standard' antivenoms. The least
      effective antivenoms had the lowest IgG content/vial. CONCLUSIONS: Manufacture
      stated preclinical efficacy statements guide decision making by physicians and
      antivenom purchasers in sub-Saharan Africa. This is because of the lack of both
      clinical data on the efficacy of most of the many antivenoms used to treat
      patients and independent preclinical assessment. Our preclinical efficacy
      assessment of antivenoms available in Kenya identifies important limitations for
      two of the most commonly-used antivenoms, and that no antivenom is preclinically
      effective against all the regionally important snakes. The potential implication
      to snakebite treatment is of serious concern in Kenya and elsewhere in sub
      Saharan Africa, and underscores the dilemma physicians face, the need for
      clinical data on antivenom efficacy and the medical and societal value of
      establishing independent preclinical antivenom-efficacy testing facilities
      throughout the continent.

PMID- 29045430
TI  - The association between herpes virus infections and functional somatic symptoms
      in a general population of adolescents. The TRAILS study.
AB  - BACKGROUND: FSS have been suggested to follow activation of the immune system,
      triggered by herpes virus infections. The aim of this study was to find out
      whether herpes virus infections were associated with the experience of FSS in
      adolescents, and whether this association was mediated by hsCRP, as a general
      marker of immune activation. METHODS: This study was performed in TRAILS, a large
      prospective population cohort of 2230 adolescents (mean age: 16.1 years, SD =
      .66, 53.4% girls). FSS were assessed using the somatic complaints subscale of the
      Youth Self-Report. FSS were analyzed as total scores and divided in two group
      clusters based on previous studies in this cohort. Levels of hsCRP and antibody
      levels to the herpes viruses HSV1, HSV2, CMV, EBV and HHV6 were assessed in blood
      samples at age 16. Also a value for pathogen burden was created adding the number
      of viruses the adolescents were seropositive for. Multiple regression analysis
      with bootstrapping was used to analyze the association between viral antibodies
      and pathogen burden, hsCRP and FSS scores. RESULTS: Antibody levels and pathogen
      burden were not associated with FSS total scores or FSS scores in both symptom
      groups. hsCRP was associated with the total FSS score (B = .02, 95% CI: .004 to
      .028, p = .01) and FSS score in the symptom group of headache and
      gastrointestinal complaints (B = .02, 95% CI: .001 to .039, p = .04). CONCLUSION:
      Our study showed no association between herpes virus infections and FSS in
      general or specific FSS symptom clusters. A role for inflammatory processes in
      FSS development was supported by the significant association we found between
      hsCRP levels and FSS, especially in the symptom group of headache and
      gastrointestinal complaints.

PMID- 29045431
TI  - Functional improvement of dystrophic muscle by repression of utrophin: let-7c
      interaction.
AB  - Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by an absence
      of the 427kD muscle-specific dystrophin isoform. Utrophin is the autosomal
      homolog of dystrophin and when overexpressed, can compensate for the absence of
      dystrophin and rescue the dystrophic phenotype of the mdx mouse model of DMD.
      Utrophin is subject to miRNA mediated repression by several miRNAs including let
      7c. Inhibition of utrophin: let-7c interaction is predicted to 'repress the
      repression' and increase utrophin expression. We developed and tested the ability
      of an oligonucleotide, composed of 2'-O-methyl modified bases on a
      phosphorothioate backbone, to anneal to the utrophin 3'UTR and prevent let-7c
      miRNA binding, thereby upregulating utrophin expression and improving the
      dystrophic phenotype in vivo. Suppression of utrophin: let-7c interaction using
      bi-weekly intraperitoneal injections of let7 site blocking oligonucleotides
      (SBOs) for 1 month in the mdx mouse model for DMD, led to increased utrophin
      expression along with improved muscle histology, decreased fibrosis and increased
      specific force. The functional improvement of dystrophic muscle achieved using
      let7-SBOs suggests a novel utrophin upregulation-based therapeutic strategy for
      DMD.

PMID- 29045432
TI  - Inflammatory response and oxidative stress during liver resection.
AB  - BACKGROUND: Postoperative complications are still a major concern after liver
      resection (LR). Systemic inflammation and deregulated reactive oxygen species
      during major abdominal surgery may impair outcome after hepatectomy. METHODS:
      Patients undergoing LR were included in this study (n = 40). Oxidative stress
      (OS) was measured peri- and post-operatively as static oxidation-reduction
      potential markers (sORP) and antioxidant capacity ORP (cORP) by using the
      RedoxSYS Diagnostic system. Furthermore, Th1- and Th2-specific cytokines were
      assessed. RESULTS: Whereas there was no significant change in systemic sORP
      during LR and in the early postoperative course, there was a substantial decrease
      of cORP immediately post-surgery, and on postoperative days 1 and 3 (p<0.001). OS
      response was tightly regulated, as there was a significant correlation between
      sORP and cORP (p<0.0001; R2:0.457). An increase of OS (sORP) after LR of more
      than 3 mV was predictive for severe postoperative complications (53.8% vs. 12.5;
      p = 0.017). There was a significantly higher IL-2 (p = 0.006) and IL-5 (p =
      0.001) increase during hepatectomy in patients who developed a severe morbidity.
      CONCLUSION: Antioxidant capacity remained stable during LR but dropped during the
      post-surgical period, suggesting a consumption of antioxidants to maintain OS
      within healthy range. Severe postoperative complications were associated with a
      pronounced inflammatory response during surgery.

PMID- 29045433
TI  - Integrated mRNA and microRNA transcriptome analyses reveal regulation of thermal
      acclimation in Gymnocypris przewalskii: A case study in Tibetan Schizothoracine
      fish.
AB  - Environmental acclimation is important episode in wildlife occupation of the high
      altitude Tibetan Plateau (TP). Transcriptome-wide studies on thermal acclimation
      mechanism in fish species are rarely revealed in Tibetan Plateau fish at high
      altitude. Thus, we used mRNA and miRNA transcriptome sequencing to investigate
      regulation of thermal acclimation in larval Tibetan naked carp, Gymnocypris
      przewalskii. We first remodeled the regulation network of mRNA and miRNA in
      thermal acclimation, and then identified differential expression of miRNAs and
      target mRNAs enriched in metabolic and digestive pathways. Interestingly, we
      identified two candidate genes contributed to normal skeletal development. The
      altered expression of these gene groups could potentially be associated with the
      developmental issues of deformity and induced larval death. Our results have
      three important implications: first, these findings provide strong evidences to
      support our hypothesis that G. przewalskii possess ability to build heat
      tolerance against the controversial issue. Second, this study shows that
      transcriptional and post-transcriptional regulations are extensively involved in
      thermal acclimation. Third, the integrated mRNA and microRNA transcriptome
      analyses provide a large number of valuable genetic resources for future studies
      on environmental stress response in G. przewalskii and as a case study in Tibetan
      Schizothoracine fish.

PMID- 29045434
TI  - Opportunities, challenges and systems requirements for developing post-abortion
      family planning services: Perceptions of service stakeholders in China.
AB  - Post-abortion family planning (PAFP) has been proposed as a key strategy to
      decrease unintended pregnancy and repeat induced abortions. However, the
      accessibility and quality of PAFP services remain a challenge in many countries
      including China where more than 10 million unintended pregnancies occur each
      year. Most of these unwanted pregnancies end in repeated induced abortions. This
      paper aims to explore service providers' perceptions of the current situation
      regarding family planning and abortion service needs, provision, utilization, and
      the feasibility and acceptability of high quality PAFP in the future. Qualitative
      methods, including in-depth interviews and focus group discussions, were used
      with family planning policy makers, health managers, and service providers. Three
      provinces-Zhejiang, Hubei and Yunnan-were purposively selected, representing
      high, medium and relatively undeveloped areas of China. A total of fifty-three in
      depth interviews and ten focus-group discussions were conducted and analysed
      thematically. Increased numbers of abortions among young, unmarried women were
      perceived as a major reason for high numbers of abortions. Participants
      attributed this to increasing socio-cultural acceptability of premarital sex, and
      simultaneously, lack of understanding or awareness of contraception among young
      people. The majority of service stakeholders acknowledged that free family
      planning services were neither targeted at, nor accessible to unmarried people.
      The extent of PAFP provision is variable and limited. However, service providers
      expressed willingness and enthusiasm towards providing PAFP services in the
      future. Three main considerations were expressed regarding the feasibility of
      developing and implementing PAFP services: policy support, human resources, and
      financial resources. The study indicated that key service stakeholders show
      demand for and perceive considerable opportunities to develop PAFP in China.
      However, changes are needed to enable the systematic development of high quality
      PAFP, including actively targeting young and unmarried people in service
      provision, obtaining policy support and increasing the investment of human and
      financial resources.

PMID- 29045435
TI  - Impact of clinical pharmacist interventions on inappropriate prophylactic acid
      suppressant use in hepatobiliary surgical patients undergoing elective
      operations.
AB  - OBJECTIVE: To evaluate the impact and cost-benefit of clinical pharmacist
      interventions on inappropriate use of prophylactic acid suppressant in
      hepatobiliary surgical patients in a Chinese tertiary hospital. METHODS: A retro
      prospective intervention study of patients undergoing elective operations was
      performed in the Department of Hepatobiliary Surgery of the Affiliated Hospital
      of Southwest Medical University. Patients admitted from October to December 2015
      and from October to December 2016, served as the pre-intervention and the post
      intervention group, respectively. Clinical pharmacist interventions in the post
      intervention group included real-time monitoring medical records and recommending
      that surgeons prescribe prophylactic acid suppressants according to the criteria
      established by the hospital administration. Then, the clinical outcomes of post
      intervention group were compared with the pre-intervention group which lacked
      pharmacist interventions. In addition, cost-benefit analysis was conducted to
      determine the economic effects of implementing the clinical pharmacist
      interventions in acid suppressant prophylaxis in perioperative period. RESULTS:
      Clinical pharmacist interventions significantly decreased the rate of the use of
      no indications for prophylactic acid suppressant and of the cases of
      inappropriate drug selection, dose, route, replacement and prolonged duration of
      prophylaxis (P < 0.05 or P < 0.001), resulting in significant increase by 10.65%
      in the percentage of cases adhering to all the criteria (P < 0.001). Moreover,
      significant reductions were found in the average usage quantity (P<0.001), mean
      cost (P = 0.03) and mean duration (P < 0.001) of prophylaxis acid suppressant.
      The ratio of the mean cost savings for acid suppressants to the mean cost of
      pharmacist time was 13.61:1. CONCLUSION: The clinical pharmacist's real-time
      interventions facilitated the rational use of prophylactic acid suppressant and
      resulted in favorable economic outcomes in hepatobiliary surgery.

PMID- 29045437
TI  - Microencapsulated fluorescent pH probe as implantable sensor for monitoring the
      physiological state of fish embryos.
AB  - In vivo physiological measurement is a major challenge in modern science and
      technology, as is environment conservation at the global scale. Proper
      toxicological testing of widely produced mixtures of chemicals is a necessary
      step in the development of new products, allowing us to minimize the human impact
      on aquatic ecosystems. However, currently available bioassay-based techniques
      utilizing small aquatic organisms such as fish embryos for toxicity testing do
      not allow assessing in time the changes in physiological parameters in the same
      individual. In this study, we introduce microencapsulated fluorescent probes as a
      promising tool for in vivo monitoring of internal pH variation in zebrafish
      embryos. The pH alteration identified under stress conditions demonstrates the
      applicability of the microencapsulated fluorescent probes for the repeated
      analysis of the embryo's physiological state. The proposed approach has strong
      potential to simultaneously measure a range of physiological characteristics
      using a set of specific fluorescent probes and to finally bring toxicological
      bioassays and related research fields to a new level of effectiveness and
      sensitivity.

PMID- 29045436
TI  - Development and characterization of novel chimeric monoclonal antibodies for
      broad spectrum neutralization of rabies virus.
AB  - Current post-exposure prophylaxis for rabies virus infection has several
      limitations in terms of supply, cost, safety, and efficacy. Attempts to replace
      human or equine rabies immune globulins (HRIG or ERIG) have been made by several
      companies and institutes. We developed potent monoclonal antibodies to neutralize
      a broad spectrum of rabies viruses by screening hybridomas received from the U.S.
      Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human
      antibodies (chimeric #7 and #17) were constructed by cloning the variable regions
      from selected hybridomas and the constant region of a human antibody. Two
      antibodies were bound to antigenic site III and I/IV, respectively, and were able
      to neutralize 51 field isolates of rabies virus that were isolated at different
      times and places such as Asia, Africa, North America, South America, and
      Australia. These two antibodies neutralize rabies viruses with high efficacy in
      an in vivo test using Syrian hamster and mouse models and show low risk for
      adverse immunogenicity.

PMID- 29045438
TI  - Gold nanorod reshaping in vitro and in vivo using a continuous wave laser.
AB  - Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics
      as they possess features which lend themselves in equal measures as contrast
      agents and catalysts for photothermal therapy. Their optical absorption spectral
      peak wavelength is determined by their size and shape. Photothermal therapy using
      GNRs is typically established using near infrared light as this allows sufficient
      penetration into the tumour matrix. Continuous wave (CW) lasers are the most
      commonly applied source of near infrared irradiation on GNRs for tumour
      photothermal therapy. It is perceived that large tumours may require fractionated
      or prolonged irradiation. However the true efficacy of repeated or protracted CW
      irradiation on tumour sites using the original sample of GNRs remains unclear. In
      this study spectroscopy and transmission electron microscopy are used to
      demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation,
      which reduces their absorption efficiency. These changes were sustained
      throughout and beyond the initial period of irradiation, resulting from a
      spectral blue-shift and a considerable diminution in the absorption peak of GNRs.
      Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs
      and analysed with electron microscopy pre- and post-CW laser irradiation. This
      phenomenon of thermally induced GNR reshaping can occur at relatively low bulk
      temperatures, well below the bulk melting point of gold. Photoacoustic monitoring
      of GNR reshaping is also evaluated as a potential clinical aid to determine GNR
      absorption and reshaping during photothermal therapy. Aggregation of particles
      was coincidentally observed following CW irradiation, which would further
      diminish the subsequent optical absorption capacity of irradiated GNRs. It is
      thus established that sequential or prolonged applications of CW laser will not
      confer any additional photothermal effect on tumours due to significant
      attenuations in the peak optical absorption properties of GNRs following primary
      laser irradiation.

PMID- 29045439
TI  - 3D reconstruction of human movement in a single projection by dynamic marker
      scaling.
AB  - The three dimensional (3D) reconstruction of movement from videos is widely
      utilized as a method for spatial analysis of movement. Several approaches exist
      for a 3D reconstruction of movement using 2D video projection, most of them
      require the use of at least two cameras as well as the application of relatively
      complex algorithms. While a few approaches also exist for 3D reconstruction of
      movement with a single camera, they are not widely implemented due to tedious and
      complicated methods of calibration. Here we propose a simple method that allows
      for a 3D reconstruction of movement by using a single projection and three
      calibration markers. Such approach is made possible by tracking the change in
      diameter of a moving spherical marker within a 2D projection. In order to test
      our model, we compared kinematic results obtained with this model to those with
      the commonly used approach of two cameras and Direct Linear Transformation (DLT).
      Our results show that such approach appears to be in line with the DLT method for
      3D reconstruction and kinematic analysis. The simplicity of this method may
      render it approachable for both clinical use as well as in uncontrolled
      environments.

PMID- 29045440
TI  - Parental depressive symptoms, children's emotional and behavioural problems, and
      parents' expressed emotion-Critical and positive comments.
AB  - This longitudinal study examined whether mothers' and fathers' depressive
      symptoms predict, independently and interactively, children's emotional and
      behavioural problems. It also examined bi-directional associations between
      parents' expressed emotion constituents (parents' child-directed positive and
      critical comments) and children's emotional and behavioural problems. At time 1,
      the sample consisted of 160 families in which 50 mothers and 40 fathers had
      depression according to the Structured Clinical Interview for DSM-IV. Children's
      mean age at Time 1 was 3.9 years (SD = 0.8). Families (n = 106) were followed up
      approximately 16 months later (Time 2). Expressed emotion constituents were
      assessed using the Preschool Five Minute Speech Sample. In total, 144 mothers and
      158 fathers at Time 1 and 93 mothers and 105 fathers at Time 2 provided speech
      samples. Fathers' depressive symptoms were concurrently associated with more
      child emotional problems when mothers had higher levels of depressive symptoms.
      When controlling for important confounders (children's gender, baseline problems,
      mothers' depressive symptoms and parents' education and age), fathers' depressive
      symptoms independently predicted higher levels of emotional and behavioural
      problems in their children over time. There was limited evidence for a bi
      directional relationship between fathers' positive comments and change in
      children's behavioural problems over time. Unexpectedly, there were no bi
      directional associations between parents' critical comments and children's
      outcomes. We conclude that the study provides evidence to support a whole family
      approach to prevention and intervention strategies for children's mental health
      and parental depression.

PMID- 29045441
TI  - Comparability of activity monitors used in Asian and Western-country studies for
      assessing free-living sedentary behaviour.
AB  - This study aims to compare the outputs of the waist-worn Active style Pro HJA
      350IT (ASP; used in studies with Asian populations), the waist-worn
      ActiGraghTMGT3X+ using the normal filter (GT3X+) and the thigh-worn activPAL3
      (AP) in assessing adults' sedentary behaviour (total sedentary time, number of
      breaks) under free-living conditions. Fifty healthy workers wore the three
      monitors simultaneously during their waking hours on two days, including a work
      day and a non-work day. Valid data were at least 10 hours of wearing time, and
      the differences between monitors on the sedentary outputs using the AP as
      criterion measurement were analyzed by ANOVA. The number of participants who had
      complete valid data for work day and non-work day was 47 and 44, respectively.
      Total sedentary time and breaks estimated by the AP were respectively 466.5 +/-
      146.8 min and 64.3 +/- 24.9 times on the work day and 497.7 +/- 138.3 min and
      44.6 +/- 15.4 times on the non-work day. In total sedentary time, the ASP
      estimated 29.7 min (95%CI = 7.9 to 51.5) significantly shorter than the AP on the
      work day but showed no significant difference against the AP on the non-work day.
      The GT3X+ estimated 80.1 min (54.6 to 105.6) and 52.3 (26.4 to 78.2)
      significantly longer than the AP on the work day and the non-work day,
      respectively. For the number of breaks from sedentary time, on both days, the ASP
      and the GT3X+ estimated significantly more than the AP: 14.1 to 15.8 times (6.3
      to 22.5) for the ASP and 27.7 to 28.8 times (21.8 to 34.8) for the GT3X+.
      Compared to the AP as the criterion, the ASP can underestimate total sedentary
      time and the GT3X+ can overestimate it, and more so at the lower levels of
      sedentary time. For breaks from sedentary time, compared to the AP, both the
      GT3X+ the ASP can overestimate.

PMID- 29045442
TI  - A semi-synthetic glycosaminoglycan analogue inhibits and reverses Plasmodium
      falciparum cytoadherence.
AB  - A feature of mature Plasmodium falciparum parasitized red blood cells is their
      ability to bind surface molecules of the microvascular endothelium via the
      parasite-derived surface protein Plasmodium falciparum erythrocyte membrane
      protein 1 (PfEMP1). This ligand is associated with the cytoadherence pathology
      observed in severe malaria. As pRBC treated with effective anti-malarial drugs
      are still able to cytoadhere, there is therefore a need to find an adjunct
      treatment that can inhibit and reverse the adhesion process. One semi-synthetic,
      sulfated polysaccharide has been identified that is capable of inhibiting and
      reversing sequestration of pRBC on endothelial cells in vitro under physiological
      flow conditions. Furthermore, it exhibits low toxicity in the intrinsic (APTT
      assay) and extrinsic (PT assay) clotting pathways, as well as exhibiting minimal
      effects on cell (HUVEC) viability (MTT proliferation assay). These findings
      suggest that carbohydrate-based anti-adhesive candidates may provide potential
      leads for therapeutics for severe malaria.

PMID- 29045443
TI  - A Lagrangian meshfree method applied to linear and nonlinear elasticity.
AB  - The repeated replacement method (RRM) is a Lagrangian meshfree method which we
      have previously applied to the Euler equations for compressible fluid flow. In
      this paper we present new enhancements to RRM, and we apply the enhanced method
      to both linear and nonlinear elasticity. We compare the results of ten test
      problems to those of analytic solvers, to demonstrate that RRM can successfully
      simulate these elastic systems without many of the requirements of traditional
      numerical methods such as numerical derivatives, equation system solvers, or
      Riemann solvers. We also show the relationship between error and computational
      effort for RRM on these systems, and compare RRM to other methods to highlight
      its strengths and weaknesses. And to further explain the two elastic equations
      used in the paper, we demonstrate the mathematical procedure used to create
      Riemann and Sedov-Taylor solvers for them, and detail the numerical techniques
      needed to embody those solvers in code.

PMID- 29045445
TI  - Occupancy modeling reveals territory-level effects of nest boxes on the presence,
      colonization, and persistence of a declining raptor in a fruit-growing region.
AB  - Nest boxes for predators in agricultural regions are an easily implemented tool
      to improve local habitat quality with potential benefits for both conservation
      and agriculture. The potential for nest boxes to increase raptor populations in
      agricultural regions is of particular interest given their positions as top
      predators. This study examined the effects of cherry orchard nest boxes on the
      local breeding population of a declining species, the American Kestrel (Falco
      sparverius), in a fruit-growing region of Michigan. During the 2013-2016 study,
      we added a total of 23 new nest boxes in addition to 24 intact boxes installed
      previously; kestrels used up to 100% of our new boxes each season. We conducted
      temporally-replicated surveys along four roadside transects divided into 1.6 km *
      500 m sites. We developed a multi-season occupancy model under a Bayesian
      framework and found that nest boxes had strong positive effects on first-year
      site occupancy, site colonization, and site persistence probabilities. The
      estimated number of occupied sites increased between 2013 and 2016, which
      correlated with the increase in number of sites with boxes. Kestrel detections
      decreased with survey date but were not affected by time of day or activity at
      the boxes themselves. These results indicate that nest boxes determined the
      presence of kestrels at our study sites and support the conclusion that the local
      kestrel population is likely limited by nest site availability. Furthermore, our
      results are highly relevant to the farmers on whose properties the boxes were
      installed, for we can conclude that installing a nest box in an orchard resulted
      in a high probability of kestrels occupying that orchard or the areas adjacent to
      it.

PMID- 29045444
TI  - The importance of public health, poverty reduction programs and women's
      empowerment in the reduction of child stunting in rural areas of Moramanga and
      Morondava, Madagascar.
AB  - BACKGROUND: Malnutrition accounts for 45% of mortality in children under five
      years old, despite a global mobilization against chronic malnutrition. In
      Madagascar, the most recent data show that the prevalence of stunting in children
      under five years old is still around 47.4%. This study aimed to identify the
      determinants of stunting in children in rural areas of Moramanga and Morondava
      districts to target the main areas for intervention. METHODS: A case-control
      study was conducted in children aged from 6 to 59.9 months, in 2014-2015. We
      measured the height and weight of mothers and children and collected data on
      child, mother and household characteristics. One stool specimen was collected
      from each child for intestinal parasite identification. We used a multivariate
      logistic regression model to identify the determinants of stunting using
      backwards stepwise methods. RESULTS: We included 894 and 932 children in
      Moramanga and in Morondava respectively. Stunting was highly prevalent in both
      areas, being 52.8% and 40.0% for Moramanga and Morondava, respectively. Stunting
      was most associated with a specific age period (12mo to 35mo) in the two study
      sites. Infection with Trichuris trichiura (aOR: 2.4, 95% CI: 1.1-5.3) and those
      belonging to poorer households (aOR: 2.3, 95% CI: 1.6-3.4) were the major risk
      factors in Moramanga. In Morondava, children whose mother had activities outside
      the household (aOR: 1.7, 95% CI: 1.2-2.5) and those perceived to be small at
      birth (aOR: 1.6, 95% CI: 1.1-2.1) were more likely to be stunted, whereas
      adequate birth spacing (>=24months) appeared protective (aOR: 0.4, 95% CI: 0.3
      0.7). CONCLUSION: Interventions that could improve children's growth in these two
      areas include poverty reduction, women's empowerment, public health programmes
      focusing on WASH and increasing acceptability, and increased coverage and quality
      of child/maternal health services.

PMID- 29045446
TI  - Changes in numbers and size of synaptic vesicles of cortical neurons induced by
      exposure to 835 MHz radiofrequency-electromagnetic field.
AB  - We studied the effects of radiofrequency electromagnetic fields (RF-EMFs)
      exposure on neuronal functions of mice. Particularly, we focused on RF-EMF
      effects on synaptic vesicles (SVs), which store neurotransmitters at axon
      terminals or synaptic boutons. C57 BL/6 mice were exposed to 835 MHz RF-EMF (4.0
      W/kg SAR, for 5 h daily) and alterations in SVs at presynaptic terminals in the
      cerebral cortex were determined. Ultrastructure of randomly selected cortical
      neurons was observed using typical electron microscopy and bio-high voltage
      electron microscopy (Bio-HVEM) methods, which enable the estimation of the
      numbers and size of SVs. The density of the SVs (number /10 MUm2 or 40 MUm3) was
      significantly decreased in the presynaptic boutons of cortical neurons after RF
      EMF exposure. Furthermore, qPCR and immunoblotting analyses revealed that the
      expression of synapsins I/II (Syns I/II) genes and proteins were significantly
      decreased in the cortical neurons of RF-EMF exposed mice. The present study
      suggested that alteration of SVs and Syn levels may result in alterations of
      neurotransmitters in the cerebral cortex following RF-EMF exposure.

PMID- 29045447
TI  - Protective effect of low-dose risedronate against osteocyte apoptosis and bone
      loss in ovariectomized rats.
AB  - Osteocyte apoptosis is the first reaction to estrogen depletion, thereby
      stimulating osteoclastic bone resorption resulting in bone loss. We investigated
      the effects of two different risedronate (RIS) doses (high and low) on osteocyte
      apoptosis, osteoclast activity and bone loss in ovariectomized rats. Forty rats
      with ovariectomy (OVX) and sham ovariectomy (SHAM) were divided into 4 groups: 1)
      SHAM rats treated with saline (SHAM); 2) OVX rats treated with saline (OVX); 3)
      OVX rats treated with low-dose RIS (OVX-LR, 0.08 MUg/kg/day); 4) OVX rats treated
      with high-dose RIS (OVX-HR, 0.8 MUg/kg/day). All animals were sacrificed 90 days
      after surgery for the examinations of osteocyte apoptosis by caspase-3 staining,
      osteoclast activity by TRAP staining and bone volume by micro-CT scanning in
      lumbar vertebral cancellous bone. Both low and high dose RIS significantly
      reduced caspase-3 positive osteocytes, empty lacunae and TRAP positive
      osteoclasts in OVX rats. Although the difference in caspase-3 positive osteocytes
      was not significant between the OVX-LR and OVX-HR groups, numerically these cells
      were significantly more prevalent in OVX-HR (not OVX-LR) group than in SHAM
      group. TRAP positive osteoclasts were significantly higher in OVX-LR group than
      in SHAM or OVX-HR group. There was no significant difference in bone volume among
      the OVX-LR, OVX-HR and SHAM groups, but lower in OVX group alone. However,
      significant increase in trabecular thickness only occurred in OVX-LR group. We
      conclude that both low and high dose RIS significantly inhibit osteocyte
      apoptosis and osteoclast activity in OVX rats, but the low-dose RIS has weaker
      effect on osteoclast activity. However, low-dose RIS preserves cancellous bone
      mass and microarchitecture as well as high-dose RIS after estrogen depletion.

PMID- 29045449
TI  - Substitutions in conserved regions preceding and within the linker affect
      activity and flexibility of tRNase ZL, the long form of tRNase Z.
AB  - The enzyme tRNase Z, a member of the metallo-beta-lactamase family,
      endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for
      CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions
      as a homodimer and is found in all prokaryotes and some eukaryotes. The long
      form, tRNase ZL, related to tRNase ZS through tandem duplication and found only
      in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS.
      tRNase ZL consists of related but diverged amino and carboxy domains connected by
      a flexible linker (also referred to as a flexible tether) and functions as a
      monomer. The amino domain retains the flexible arm responsible for substrate
      recognition and binding while the carboxy domain retains the active site. The
      linker region was explored by Ala-scanning through two conserved regions of D.
      melanogaster tRNase Z: NdomTprox, located at the carboxy end of the amino domain
      proximal to the linker, and Tflex, a flexible site in the linker. Periodic
      substitutions in a hydrophobic patch (F329 and L332) at the carboxy end of
      NdomTprox show 2,700 and 670-fold impairment relative to wild type, respectively,
      accompanied by reduced linker flexibility at N-T inside the Ndom- linker
      boundary. The Ala substitution for N378 in the Tflex region has 10-fold higher
      catalytic efficiency than wild type and locally decreased flexibility, while the
      Ala substitution at R382 reduces catalytic efficiency ~50-fold. These changes in
      pre-tRNA processing kinetics and protein flexibility are interpreted in light of
      a recent crystal structure for S. cerevisiae tRNase Z, suggesting transmission of
      local changes in hydrophobicity into the skeleton of the amino domain.

PMID- 29045448
TI  - Interferon-free therapy with direct acting antivirals for HCV/HIV-1 co-infected
      Japanese patients with inherited bleeding disorders.
AB  - INTRODUCTION: Almost 30 years ago, about 30% of Japanese hemophiliacs became
      infected with HIV-1 and hepatitis C virus (HCV) after receiving contaminated
      blood products. While several studies have reported the high efficacy and safety
      of direct acting antivirals (DAA) in HIV-1 co-infected patients, such data are
      limited in hemophiliacs. METHODS: We conducted a single-center, open-label study
      involving 27 Japanese patients (median age; 45 years) with inherited bleeding
      disorders who were co-infected with HCV/HIV-1. Patients with HCV genotype 1 (GT1)
      and GT4 received ledipasvir (90 mg) plus sofosbuvir (400 mg), those with HCV GT2
      received sofosbuvir plus weight-based ribavirin, and those with HCV GT3 received
      daclatasvir (60 mg) plus sofosbuvir. Treatment was continued for 12 weeks in all
      patients. The primary endpoints were rate of sustained virologic response at 12
      weeks after end of therapy (SVR12) and occurrence of adverse events during DAA
      therapy. RESULTS: Eighteen (67%) patients had had received interferon-based
      therapy, and 11 (41%) had compensated cirrhosis. HCV genotypes were GT1a 4 (15%),
      GT1b 16 (59%), GT1 undetermined 2 (7%), GT2a 1 (4%), GT3a 3 (11%) and GT4a 1
      (4%). All patients were on combination antiretroviral therapy (cART) and had
      undetectable HIV-1 viral load (<20 copies/MUL) at baseline. All patients achieved
      SVR12. Serious adverse events were observed in 3 patients: arteritis of the leg,
      which resolved after completion of DAA therapy, asymptomatic QT prolongation and
      gastrointestinal hemorrhage. cART failure was noted in one patient due to
      emergence of raltegravir resistance during ledipasvir/sofosbuvir treatment.
      Although alpha-fetoprotein, Mac-2 binding protein glycosylation isomer (M2BPGi),
      and Fibro Scan (FS) scores decreased in most patients during DAA therapy, M2BPGi
      (>2.0 cutoff index) and FS scores (>15.0 kPa) were still high in 6 patients at
      week 36. CONCLUSIONS: DAA therapy is effective in all patients. However, adverse
      events and efficacy of cART should be monitored closely.

PMID- 29045450
TI  - The genetics and development of mandibles and hypopharyngeal sclerite and cornua
      in larvae of Drosophila gaucha.
AB  - The genetics and epigenetic processes associated with morphological organization
      are a principal aim of biology, ranging from cohesion between cells to shape and
      size of organisms. We investigate the post-embryonic development of
      Hypopharyngeal sclerite and cornua HPC and mandibles M of Drosophila gaucha
      larva. Integrated functioning of these Cephalopharyngeal skeleton parts of D.
      gaucha larva is essential for food acquisition, participating in locomotion and
      microhabitat selection. We examined two isolates by recording the growth of the
      HPC and M every 24 h for 8 days in parental, F1, F2 and backcross larvae. In F1
      larvae, the HPC and M growth was similar to the parental. In F2 and backcross
      larvae, the growth was slower. Epistasis and dominance are the principal sources
      upon which the growth of HPC and M are based. Pleiotropic genes seem also to be
      involved in integrating the development of M and HPC. Our data suggest that
      hybridization of the isolates modified epigenetic processes involved in the
      development of those morphological structures of D. gaucha larva.

PMID- 29045451
TI  - Getting to the heart of the matter: Does aberrant interoceptive processing
      contribute towards emotional eating?
AB  - According to estimates from Public Health England, by 2034 70% of adults are
      expected to be overweight or obese, therefore understanding the underpinning
      aetiology is a priority. Eating in response to negative affect contributes
      towards obesity, however, little is known about the underlying mechanisms.
      Evidence that visceral afferent signals contribute towards the experience of
      emotion is accumulating rapidly, with the emergence of new influential models of
      'active inference'. No longer viewed as a 'bottom up' process, new interoceptive
      facets based on 'top down' predictions have been proposed, although at present it
      is unclear which aspects of interoception contribute to aberrant eating behaviour
      and obesity. Study one examined the link between eating behaviour, body mass
      index and the novel interoceptive indices; interoceptive metacognitive awareness
      (IAw) and interoceptive prediction error (IPE), as well as the traditional
      measures; interoceptive accuracy (IAc) and interoceptive sensibility (IS). The
      dissociation between these interoceptive indices was confirmed. Emotional eaters
      were characterised by a heightened interoceptive signal but reduced meta
      cognitive awareness of their interoceptive abilities. In addition, emotional
      eating correlated with IPE; effects that could not be accounted for by
      differences in anxiety and depression. Study two confirmed the positive
      association between interoceptive accuracy and emotional eating using a novel
      unbiased heartbeat discrimination task based on the method of constant stimuli.
      Results reveal new and important mechanistic insights into the processes that may
      underlie problematic affect regulation in overweight populations.

PMID- 29045452
TI  - Prospective, multicenter French study evaluating the clinical impact of the
      Breast Cancer Intrinsic Subtype-Prosigna(r) Test in the management of early-stage
      breast cancers.
AB  - PURPOSE: The Prosigna(r) breast cancer prognostic gene signature assay identifies
      a gene-expression profile that permits the classification of tumors into subtypes
      and gives a score for the risk of recurrence (ROR) at 10 years. The primary
      objective of this multicenter study was to evaluate the impact of Prosigna's
      assay information on physicians' adjuvant treatment decisions in patients with
      early-stage breast cancer. Secondary objectives were to assess confidence of
      practitioners in their therapeutic recommendations before and after the added
      information provided by the Prosigna assay; and to evaluate the emotional state
      of patients before and after the Prosigna test results. METHODS: Consecutive
      patients with invasive early-stage breast cancer were enrolled in a prospective,
      observational, multicenter study carried out in 8 hospitals in France. The
      Prosigna test was carried out on surgical specimens using the nCounter(r)
      Analysis System located at the Institut Curie. Both before and after receiving
      the Prosigna test results, physicians completed treatment confidence
      questionnaires and patients completed questionnaires concerning their state of
      anxiety, the difficulties felt in face of the therapy and quality of life.
      Information was also collected at 6 months regarding the physicians' opinion on
      the test results and the patients' degree of anxiety, difficulties with therapy
      and quality of life. RESULTS: Between March 2015 and January 2016, 8 study
      centers in France consecutively enrolled 210 postmenopausal women with estrogen
      receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and
      node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as
      assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1
      (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the
      Prosigna test results, physicians categorized tumor subtypes based on
      immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70
      (36%) patients, an overall discordance rate of 25%. The availability of Prosigna
      assay results was significantly associated with the likelihood of change in
      treatment recommendations, with 34 patients (18%) having their treatment plan
      changed from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa
      (p<0.001, Fisher's exact test). Prosigna test results also decreased patients'
      anxiety about the chosen adjuvant therapy, and improved emotional well-being and
      measures of personal perceptions of uncertainty. CONCLUSIONS: The results of this
      prospective decision impact study are consistent with 2 previous, identically
      designed studies carried out in Spain and Germany. The availability of Prosigna
      test results increased the confidence of treating physicians in their adjuvant
      treatment decisions, and led to an 18% change in chemotherapy treatment plan
      (from Adjuvant Chemotherapy to No Adjuvant Chemotherapy or vice versa). Prosigna
      testing decreased anxiety and improved measures of health-related quality of life
      in patients facing adjuvant therapy. The 25% discordance between Prosigna test
      and IHC subtyping underlines the importance of molecular testing for optimal
      systemic therapy indications in early breast cancer.

PMID- 29045453
TI  - CRISPR/Cas-mediated knock-in via non-homologous end-joining in the crustacean
      Daphnia magna.
AB  - The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated system (Cas) is widely used for mediating the knock-in of foreign DNA
      into the genomes of various organisms. Here, we report a process of CRISPR/Cas
      mediated knock-in via non-homologous end joining by the direct injection of
      Cas9/gRNA ribonucleoproteins (RNPs) in the crustacean Daphnia magna, which is a
      model organism for studies on toxicology, ecology, and evolution. First, we
      confirmed the cleavage activity of Cas9 RNPs comprising purified Cas9 proteins
      and gRNAs in D. magna. We used a gRNA that targets exon 10 of the eyeless gene.
      Cas9 proteins were incubated with the gRNAs and the resulting Cas9 RNPs were
      injected into D. magna eggs, which led to a typical phenotype of the eyeless
      mutant, i.e., eye deformity. The somatic and heritable mutagenesis efficiencies
      were up to 96% and 40%, respectively. Second, we tested the CRISPR/Cas-mediated
      knock-in of a plasmid by the injection of Cas9 RNPs. The donor DNA plasmid
      harboring the fluorescent reporter gene was designed to contain the gRNA
      recognition site. The co-injection of Cas9 RNPs together with the donor DNAs
      resulted in generation of one founder animal that produced fluorescent progenies.
      This transgenic Daphnia had donor DNA at the targeted genomic site, which
      suggested the concurrent cleavage of the injected plasmid DNA and genomic DNA.
      Owing to its simplicity and ease of experimental design, we suggest that the
      CRISPR/Cas-mediated knock-in method represents a promising tool for studying
      functional genomics in D. magna.

PMID- 29045454
TI  - Insights into the inhibited form of the redox-sensitive SufE-like sulfur acceptor
      CsdE.
AB  - Sulfur trafficking in living organisms relies on transpersulfuration reactions
      consisting in the enzyme-catalyzed transfer of S atoms via activated persulfidic
      S across protein-protein interfaces. The recent elucidation of the mechanistic
      basis for transpersulfuration in the CsdA-CsdE model system has paved the way for
      a better understanding of its role under oxidative stress. Herein we present the
      crystal structure of the oxidized, inactivated CsdE dimer at 2.4 A resolution.
      The structure sheds light into the activation of the Cys61 nucleophile on its way
      from a solvent-secluded position in free CsdE to a fully extended conformation in
      the persulfurated CsdA-CsdE complex. Molecular dynamics simulations of available
      CsdE structures allow to delineate the sequence of conformational changes
      underwent by CsdE and to pinpoint the key role played by the deprotonation of the
      Cys61 thiol. The low-energy subunit orientation in the disulfide-bridged CsdE
      dimer demonstrates the likely physiologic relevance of this oxidative dead-end
      form of CsdE, suggesting that CsdE could act as a redox sensor in vivo.

PMID- 29045455
TI  - Relative contributions of norspermidine synthesis and signaling pathways to the
      regulation of Vibrio cholerae biofilm formation.
AB  - The polyamine norspermidine is one of the major polyamines synthesized by
      Vibrionales and has also been found in various aquatic organisms. Norspermidine
      is among the environmental signals that positively regulate Vibrio cholerae
      biofilm formation. The NspS/MbaA signaling complex detects extracellular
      norspermidine and mediates the response to this polyamine. Norspermidine binding
      to the NspS periplasmic binding protein is thought to inhibit the
      phosphodiesterase activity of MbaA, increasing levels of the biofilm-promoting
      second messenger cyclic diguanylate monophosphate, thus enhancing biofilm
      formation. V. cholerae can also synthesize norspermidine using the enzyme NspC as
      well as import it from the environment. Deletion of the nspC gene was shown to
      reduce accumulation of bacteria in biofilms, leading to the conclusion that
      intracellular norspermidine is also a positive regulator of biofilm formation.
      Because V. cholerae uses norspermidine to synthesize the siderophore vibriobactin
      it is possible that intracellular norspermidine is required to obtain sufficient
      amounts of iron, which is also necessary for robust biofilm formation. The
      objective of this study was to assess the relative contributions of intracellular
      and extracellular norspermidine to the regulation of biofilm formation in V.
      cholerae. We show the biofilm defect of norspermidine synthesis mutants does not
      result from an inability to produce vibriobactin as vibriobactin synthesis
      mutants do not have diminished biofilm forming abilities. Furthermore, our work
      shows that extracellular, but not intracellular norspermidine, is mainly
      responsible for promoting biofilm formation. We establish that the NspS/MbaA
      signaling complex is the dominant mediator of biofilm formation in response to
      extracellular norspermidine, rather than norspermidine synthesized by NspC or
      imported into the cell.

PMID- 29045456
TI  - Inference of epidemiological parameters from household stratified data.
AB  - We consider a continuous-time Markov chain model of SIR disease dynamics with two
      levels of mixing. For this so-called stochastic households model, we provide two
      methods for inferring the model parameters-governing within-household
      transmission, recovery, and between-household transmission-from data of the day
      upon which each individual became infectious and the household in which each
      infection occurred, as might be available from First Few Hundred studies. Each
      method is a form of Bayesian Markov Chain Monte Carlo that allows us to calculate
      a joint posterior distribution for all parameters and hence the household
      reproduction number and the early growth rate of the epidemic. The first method
      performs exact Bayesian inference using a standard data-augmentation approach;
      the second performs approximate Bayesian inference based on a likelihood
      approximation derived from branching processes. These methods are compared for
      computational efficiency and posteriors from each are compared. The branching
      process is shown to be a good approximation and remains computationally efficient
      as the amount of data is increased.

PMID- 29045457
TI  - Dietary vitamin D3 deficiency exacerbates sinonasal inflammation and alters local
      25(OH)D3 metabolism.
AB  - RATIONALE: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have
      been shown to be vitamin D3 (VD3) deficient, which is associated with more severe
      disease and increased polyp size. To gain mechanistic insights into these
      observational studies, we examined the impact of VD3 deficiency on inflammation
      and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic
      rhinosinusitis (Af-CRS). METHODS: Balb/c mice were fed control or VD3 deficient
      diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week
      later given Af intranasally every three days for four weeks while being
      maintained on control or VD3 deficient diet. Airway function, sinonasal immune
      cell infiltrate and sinonasal VD3 metabolism profiles were then examined.
      RESULTS: Mice with VD3 deficiency had increased Penh and sRaw values as compared
      to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As
      compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1alpha
      hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of
      nasal lavage samples showed that VD3 deficiency alone and in combination with Af
      CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3
      deficiency exacerbated increases in monocyte-derived dendritic cell (DC)
      associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af
      CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did
      not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a
      modifying or exacerbating impact on nasal lavage levels of IFN-gamma, IL-6, IL-10
      and TNF-alpha, but had no impact on IL-17A. CONCLUSIONS: VD3 deficiency causes
      changes in sinonasal immunity, which in many ways mirrors the changes observed in
      Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3
      deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism
      causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3,
      even with adequate circulating levels.

PMID- 29045459
TI  - Microbial composition analyses by 16S rRNA sequencing: A proof of concept
      approach to provenance determination of archaeological ochre.
AB  - Many archaeological science studies use the concept of "provenance", where the
      origins of cultural material can be determined through physical or chemical
      properties that relate back to the origins of the material. Recent studies using
      DNA profiling of bacteria have been used for the forensic determination of soils,
      towards determination of geographic origin. This manuscript presents a novel
      approach to the provenance of archaeological minerals and related materials
      through the use of 16S rRNA sequencing analysis of microbial DNA. Through the
      microbial DNA characterization from ochre and multivariate statistics, we have
      demonstrated the clear discrimination between four distinct Australian cultural
      ochre sites.

PMID- 29045458
TI  - Individual differences in responsivity to social rewards: Insights from two eye
      tracking tasks.
AB  - Humans generally prefer social over nonsocial stimuli from an early age. Reduced
      preference for social rewards has been observed in individuals with autism
      spectrum conditions (ASC). This preference has typically been noted in separate
      tasks that measure orienting toward and engaging with social stimuli. In this
      experiment, we used two eye-tracking tasks to index both of these aspects of
      social preference in in 77 typical adults. We used two measures, global effect
      and preferential looking time. The global effect task measures saccadic deviation
      toward a social stimulus (related to 'orienting'), while the preferential looking
      task records gaze duration bias toward social stimuli (relating to 'engaging').
      Social rewards were found to elicit greater saccadic deviation and greater gaze
      duration bias, suggesting that they have both greater salience and higher value
      compared to nonsocial rewards. Trait empathy was positively correlated with the
      measure of relative value of social rewards, but not with their salience. This
      study thus elucidates the relationship of empathy with social reward processing.

PMID- 29045461
TI  - Past alcohol consumption and incident atrial fibrillation: The Atherosclerosis
      Risk in Communities (ARIC) Study.
AB  - BACKGROUND: Although current alcohol consumption is a risk factor for incident
      atrial fibrillation (AF), the more clinically relevant question may be whether
      alcohol cessation is associated with a reduced risk. METHODS AND RESULTS: We
      studied participants enrolled in the Atherosclerosis Risk in Communities Study
      (ARIC) between 1987 and 1989 without prevalent AF. Past and current alcohol
      consumption were ascertained at baseline and at 3 subsequent visits. Incident AF
      was ascertained via study ECGs, hospital discharge ICD-9 codes, and death
      certificates. Of 15,222 participants, 2,886 (19.0%) were former drinkers. During
      a median follow-up of 19.7 years, there were 1,631 cases of incident AF, 370
      occurring in former consumers. Former drinkers had a higher rate of AF compared
      to lifetime abstainers and current drinkers. After adjustment for potential
      confounders, every decade abstinent from alcohol was associated with an
      approximate 20% (95% CI 11-28%) lower rate of incident AF; every additional
      decade of past alcohol consumption was associated with a 13% (95% CI 3-25%)
      higher rate of AF; and every additional drink per day during former drinking was
      associated with a 4% (95% CI 0-8%) higher rate of AF. CONCLUSIONS: Among former
      drinkers, the number of years of drinking and the amount of alcohol consumed may
      each confer an increased risk of AF. Given that a longer duration of abstinence
      was associated with a decreased risk of AF, earlier modification of alcohol use
      may have a greater influence on AF prevention.

PMID- 29045460
TI  - Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective
      vaccine against breast cancer in mice xenograft model.
AB  - One of the challenging issues in vaccine development is peptide and adjuvant
      delivery into target cells. In this study, we developed a vaccine and therapeutic
      delivery system to increase cytotoxic T lymphocyte (CTL) response against a
      breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was
      conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes
      composed of DMPC, DMPG phospholipids, and fusogenic lipid
      dioleoylphosphatidylethanolamine (DOPE) containing monophosphoryl lipid A (MPL)
      adjuvant (DMPC-DMPG-DOPE-MPL-Gp2). BALB/c mice were immunized with different
      formulations and the immune response was evaluated in vitro and in vivo. ELISpot
      and intracellular cytokine analysis by flow cytometry showed that the mice
      vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-gamma+ in CD8+
      cells and CTL response. The immunization led to lower tumor sizes and longer
      survival time compared to the other groups of mice immunized and treated with the
      Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments.
      These results showed that co-formulation of DOPE and MPL conjugated with GP2
      peptide not only induces high antitumor immunity but also enhances therapeutic
      efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising
      vaccine and a therapeutic delivery system against HER2 positive cancers and
      merits further investigation.

PMID- 29045462
TI  - Correction: Temporal causal inference with stochastic audiovisual sequences.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183776.].

PMID- 29045463
TI  - Submillisievert standard-pitch CT pulmonary angiography with ultra-low dose
      contrast media administration: A comparison to standard CT imaging.
AB  - OBJECTIVES: To evaluate the image quality and radiation dose of submillisievert
      standard-pitch CT pulmonary angiography (CTPA) with ultra-low dose contrast media
      administration in comparison to standard CTPA. MATERIALS AND METHODS: Hundred
      patients (56 females, 44 males, mean age 69.6+/-15.4 years; median BMI: 26.6,
      IQR: 5.9) with suspected pulmonary embolism were examined with two different
      protocols (n = 50 each, group A: 80 kVp, ref. mAs 115, 25 ml of contrast medium;
      group B: 100 kVp, ref. mAs 150, 60 ml of contrast medium) using a dual-source CT
      equipped with automated exposure control. Objective and subjective image
      qualities, radiation exposure as well as the frequency of pulmonary embolism were
      evaluated. RESULTS: There was no significant difference in subjective image
      quality scores between two groups regarding pulmonary arteries (p = 0.776),
      whereby the interobserver agreement was excellent (group A: k = 0.9; group B k =
      1.0). Objective image analysis revealed that signal intensities (SI), signal-to
      noise ratio (SNR) and contrast-to-noise ratio (CNR) of the pulmonary arteries
      were equal or significantly higher in group B. There was no significant
      difference in the frequency of pulmonary embolism (p = 0.65). Using the low dose
      and low contrast media protocol resulted in a radiation dose reduction by 71.8%
      (2.4 vs. 0.7 mSv; p<0.001). CONCLUSIONS: This 80 kVp standard pitch CTPA protocol
      with 25 ml contrast agent volume can obtain sufficient image quality to exclude
      or diagnose pulmonary emboli while reducing radiation dose by approximately 71%.

PMID- 29045464
TI  - TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT
      promoter.
AB  - HIV1-TAT interactive protein (TIP60) is a haploinsufficient tumor suppressor.
      However, the potential mechanisms endowing its tumor suppressor ability remain
      incompletely understood. It plays a vital role in virus-induced cancers where
      TIP60 down-regulates the expression of human papillomavirus (HPV) oncoprotein E6
      which in turn destabilizes TIP60. This intrigued us to identify the role of
      TIP60, in the context of a viral infection, where it is targeted by oncoproteins.
      Through an array of molecular biology techniques such as Chromatin
      immunoprecipitation, expression analysis and mass spectrometry, we establish the
      hitherto unknown role of TIP60 in repressing the expression of the catalytic
      subunit of the human telomerase complex, TERT, a key driver for immortalization.
      TIP60 acetylates Sp1 at K639, thus inhibiting Sp1 binding to the TERT promoter.
      We identified that TIP60-mediated growth suppression of HPV-induced cervical
      cancer is mediated in part due to TERT repression through Sp1 acetylation. In
      summary, our study has identified a novel substrate for TIP60 catalytic activity
      and a unique repressive mechanism acting at the TERT promoter in virus-induced
      malignancies.

PMID- 29045465
TI  - Identifying protein complex by integrating characteristic of core-attachment into
      dynamic PPI network.
AB  - How to identify protein complex is an important and challenging task in
      proteomics. It would make great contribution to our knowledge of molecular
      mechanism in cell life activities. However, the inherent organization and dynamic
      characteristic of cell system have rarely been incorporated into the existing
      algorithms for detecting protein complexes because of the limitation of protein
      protein interaction (PPI) data produced by high throughput techniques. The
      availability of time course gene expression profile enables us to uncover the
      dynamics of molecular networks and improve the detection of protein complexes. In
      order to achieve this goal, this paper proposes a novel algorithm DCA (Dynamic
      Core-Attachment). It detects protein-complex core comprising of continually
      expressed and highly connected proteins in dynamic PPI network, and then the
      protein complex is formed by including the attachments with high adhesion into
      the core. The integration of core-attachment feature into the dynamic PPI network
      is responsible for the superiority of our algorithm. DCA has been applied on two
      different yeast dynamic PPI networks and the experimental results show that it
      performs significantly better than the state-of-the-art techniques in terms of
      prediction accuracy, hF-measure and statistical significance in biology. In
      addition, the identified complexes with strong biological significance provide
      potential candidate complexes for biologists to validate.

PMID- 29045466
TI  - Factors predicting cardiovascular events in chronic kidney disease patients. Role
      of subclinical atheromatosis extent assessed by vascular ultrasound.
AB  - Patients with chronic kidney disease (CKD) have an increased incidence of
      cardiovascular events (CVE). The contribution of subclinical atheromatosis
      extent, including femoral arteries, to CVE in CKD patients has not been
      investigated. In this paper, we examine the prognostic value of subclinical
      atheromatosis extent, assessed as the number of arterial territories with plaque,
      in predicting the incidence of major and minor CVE. The NEFRONA is a multicenter,
      prospective cohorts study that recruited 2445 CKD subjects and 559 controls, free
      from previous cardiovascular disease, in 81 medical centers across Spain. The
      presence of atheroma plaque was assessed by arterial ultrasound in ten arterial
      territories (carotid and femoral). The predictive power of the presence or
      absence of atheroma plaque in any territory was compared with the quantification
      of atheroma extent as the number of territories with plaque. During the median
      follow up of 48 months, 216 CVE were reported. Factors predicting the incidence
      of CVE in the whole cohort were being male, CKD patient, lower levels of 25(OH)
      vitamin D, higher levels of cholesterol and the extent of subclinical
      atheromatosis, yielding a higher concordance (C) index than the presence or
      absence of plaque. In stratified analysis including specific factors of CKD
      patients not on dialysis, the variables predicting CVE were the same as in the
      whole cohort, plus higher levels of potassium. Again, the inclusion of the
      information about atheromatosis as number of territories with plaque, presented a
      higher C index than the presence or absence of plaque. In the dialysis
      population, significant variables were older age, diabetes, dialysis vintage and
      higher levels of cholesterol and phosphate. In this case the higher C index was
      obtained with the information about plaque presence. Subclinical atheromatosis
      extent, including femoral arteries, influences CVE in CKD and its detection could
      improve the prediction of cardiovascular events.

PMID- 29045467
TI  - The dose of hydroxyethyl starch 6% 130/0.4 for fluid therapy and the incidence of
      acute kidney injury after cardiac surgery: A retrospective matched study.
AB  - The safety of hydroxyethyl starches (HES) is still under debate. No studies have
      compared different dosing regimens of HES in cardiac surgery. We analyzed whether
      the incidence of Acute Kidney Injury (AKI) differed taking into account a weight
      adjusted cumulative dose of HES 6% 130/0.4 for perioperative fluid therapy. This
      retrospective cohort study included all adult patients undergoing elective or
      emergency cardiac surgery with or without cardiopulmonary bypass. Exclusion
      criteria were patients on renal replacement therapy (RRT), cardiac trauma
      surgery, heart transplantation, patients with ventricular assist devices,
      subjects who required a surgical revision for bleeding and those whose medical
      records were incomplete. Primary endpoint was AKI following the creatinine based
      RIFLE classification. Secondary endpoints were 30-day mortality and RRT. Patients
      were divided into 2 groups whether they had received a cumulative HES dose of <
      30 mL/kg (Low HES) or >= 30 mL/kg (High HES) during the intra- and postoperative
      period. A total of 1501 patients were analyzed with 983 patients in the Low HES
      and 518 subjects in the High HES group. 185 (18.8%) patients in the Low HES and
      119 (23.0%) patients in the High HES group developed AKI (P = 0.06). In
      multivariable regression analysis the dose of HES administered per weight was not
      associated with AKI. After case-control matching 217 patients were analyzed in
      each group. AKI occurred in 39 (18.0%) patients in the Low HES and 50 (23.0%)
      patients in the High HES group (P = 0.19). In conditional regression analysis
      performed on the matched groups a lower weight-adjusted dose of HES was
      significantly associated with a reduced incidence of AKI [(Odds Ratio (95% CI) =
      0.825 (0.727-0.936); P = 0.003]. In the absence of any safety study the
      cumulative dose of modern HES in cardiac surgery should be kept less than 30
      mL/kg.

PMID- 29045469
TI  - Incident experience predicts freezing-like responses in firefighters.
AB  - Freezing is a defensive response to acute stress that is associated with coping
      and alterations in attentional processing. However, it remains unclear whether
      individuals in high risk professions, who are skilled at making rapid decisions
      in emergency situations, show altered threat-induced freezing. Here we
      investigated the effect of incident experience in a high risk profession on
      freezing. Additionally, we explored whether any effect of incident experience on
      freezing would be different for profession-related and -unrelated threat. Forty
      experienced and inexperienced firefighters were presented neutral, pleasant,
      related-unpleasant, and unrelated-unpleasant pictures in a passive viewing task.
      Postural sway and heart rate were assessed to determine freezing. Both postural
      and heart rate data evidenced reduced freezing upon unpleasant pictures in the
      experienced versus the inexperienced group. Relatedness of the unpleasant
      pictures did not modulate these effects. These findings indicate that higher
      incident experience relates to decreased threat-induced freezing, at least in a
      passive task context. This might suggest that primary defense responses are
      malleable through experience. Finally, these findings demonstrate the potential
      of using animal to human translational approaches to investigate defensive
      behaviors in relation to incident experience in high risk professions and
      stimulate future research on the role of freezing in resilience and coping.

PMID- 29045468
TI  - Cordycepin promotes apoptosis in renal carcinoma cells by activating the MKK7-JNK
      signaling pathway through inhibition of c-FLIPL expression.
AB  - Cellular FLICE inhibitory protein (c-FLIP) is a key anti-apoptotic regulator that
      associates with the signaling complex downstream of NF-kappaB, negatively
      interfering with apoptotic signaling. The role of c-FLIP downregulation by
      negative regulation of NF-kappaB signaling during apoptosis is poorly understood.
      Here, we demonstrate that NF-kappaB-mediated c-FLIPL negatively regulates the JNK
      signaling pathway, and that cordycepin treatment of human renal cancer cells
      leads to apoptosis induction through c-FLIPL inhibition. TNF-alpha-induced
      inflammatory microenvironments stimulated NF-kappaB signaling and the c-FLIP long
      form (c-FLIPL) in TK-10 cells. Specifically, cordycepin inhibited TNF-alpha
      mediated NF-kappaB activation, which induced renal cancer cell apoptosis.
      Cordycepin downregulated GADD45B and c-FLIPL, but upregulated MKK7 and phospho
      JNK, by preventing nuclear mobilization of NF-kappaB. Furthermore, siRNA-mediated
      knockdown of GADD45B in cordycepin-treated TK-10 cells considerably increased
      MKK7 compared to cordycepin alone. siRNA-mediated knockdown of c-FLIPL prevented
      TNF-alpha-induced JNK inactivation, whereas c-FLIPL overexpression inhibited
      cordycepin-mediated JNK activation. The JNK inhibitor SP600125 strongly inhibited
      Bax expression. In nude mice, cordycepin significantly decreased tumor volume.
      Taken together, the results indicate that cordycepin inhibits TNF-alpha-mediated
      NF-kappaB/GADD45B signaling, which activates the MKK7-JNK signaling pathway
      through inhibition of c-FLIPL expression, thus inducing TK-10 cell apoptosis.

PMID- 29045470
TI  - Structural and functional analysis of SMO-1, the SUMO homolog in Caenorhabditis
      elegans.
AB  - SUMO proteins are important post-translational modifiers involved in multiple
      cellular pathways in eukaryotes, especially during the different developmental
      stages in multicellular organisms. The nematode C. elegans is a well known model
      system for studying metazoan development and has a single SUMO homolog, SMO-1.
      Interestingly, SMO-1 modification is linked to embryogenesis and development in
      the nematode. However, high-resolution information about SMO-1 and the mechanism
      of its conjugation is lacking. In this work, we report the high-resolution three
      dimensional structure of SMO-1 solved by NMR spectroscopy. SMO-1 has flexible N
      terminal and C-terminal tails on either side of a rigid beta-grasp folded core.
      While the sequence of SMO-1 is more similar to SUMO1, the electrostatic surface
      features of SMO-1 resemble more with SUMO2/3. SMO-1 can bind to typical SUMO
      Interacting Motifs (SIMs). SMO-1 can also conjugate to a typical SUMOylation
      consensus site as well as to its natural substrate HMR-1. Poly-SMO-1 chains were
      observed in-vitro even though SMO-1 lacks any consensus SUMOylation site. Typical
      deSUMOylation enzymes like Senp2 can cleave the poly-SMO-1 chains. Despite being
      a single gene, the SMO-1 structure allows it to function in a large repertoire of
      signaling pathways involving SUMO in C. elegans. Structural and functional
      features of SMO-1 studies described here will be useful to understand its role in
      development.

PMID- 29045472
TI  - Sulfites inhibit the growth of four species of beneficial gut bacteria at
      concentrations regarded as safe for food.
AB  - Sulfites and other preservatives are considered food additives to limit bacterial
      contamination, and are generally regarded as safe for consumption by governmental
      regulatory agencies at concentrations up to 5000 parts per million (ppm).
      Consumption of bactericidal and bacteriostatic drugs have been shown to damage
      beneficial bacteria in the human gut and this damage has been associated with
      several diseases. In the present study, bactericidal and bacteriostatic effects
      of two common food preservatives, sodium bisulfite and sodium sulfite, were
      tested on four known beneficial bacterial species common as probiotics and
      members of the human gut microbiota. Lactobacillus species casei, plantarum and
      rhamnosus, and Streptococcus thermophilus were grown under optimal environmental
      conditions to achieve early log phase at start of experiments. Bacterial cultures
      were challenged with sulfite concentrations ranging between 10 and 3780 ppm for
      six hours. To establish a control, a culture of each species was inoculated into
      media containing no sulfite preservative. By two hours of exposure, a substantial
      decrease (or no increase) of cell numbers (based on OD600 readings) were observed
      for all bacteria types, in concentrations of sulfites between 250-500 ppm,
      compared to cells in sulfite free media. Further testing using serial dilution
      and drop plates identified bactericidal effects in concentrations ranging between
      1000-3780 ppm on all the Lactobacillus species by 4 hours of exposure and
      bactericidal effects on S. thermophilus in 2000ppm NaHSO3 after 6 hours of
      exposure.

PMID- 29045471
TI  - Parental and offspring contribution of genetic markers of adult blood pressure in
      early life: The FAMILY study.
AB  - Previous genome wide association studies (GWAS) identified associations of
      multiple common variants with diastolic and systolic blood pressure traits in
      adults. However, the contribution of these loci to variations of blood pressure
      in early life is unclear. We assessed the child and parental contributions of 33
      GWAS single-nucleotide polymorphisms (SNPs) for blood pressure in 1,525
      participants (515 children, 406 mothers and 237 fathers) of the Family
      Atherosclerosis Monitoring In early life (FAMILY) study followed-up for 5 years.
      Two genotype scores for systolic (29 SNPs) and diastolic (24 SNPs) blood pressure
      were built. Linear mixed-effect regressions showed significant association
      between rs1378942 in CSK and systolic blood pressure (beta = 0.98+/-0.46, P =
      3.4*10-2). The child genotype scores for diastolic and systolic blood pressure
      were not associated in children. Nominally significant parental genetic effects
      were found between the SNPs rs11191548 (CYP17A1) (paternal, beta = 2.78+/-1.49, P
      = 6.1*10-2 for SBP and beta = 3.60+/-1.24, P = 3.7*10-3 for DBP), rs17367504
      (MTHFR) (paternal, beta = 2.42+/-0.93, P = 9.3*10-3 for SBP and beta = 1.89+/
      0.80, P = 1.8*10-2 for DBP and maternal, beta = -1.32+/-0.60, P = 2.9*10-2 and
      beta = -1.97+/-0.77, P = 1.0*10-2, for SBP and DBP respectively) and child blood
      pressure. Our study supports the view that adult GWAS loci have a limited impact
      on blood pressure during the five first years of life. The parental genetic
      effects observed on blood pressure in children may suggest epigenetic mechanisms
      in the transmission of the risk of hypertension. Further replication is needed to
      confirm our results.

PMID- 29045473
TI  - Identification of functionally important microRNAs from rice inflorescence at
      heading stage of a qDTY4.1-QTL bearing Near Isogenic Line under drought
      conditions.
AB  - A cross between IR64 (high-yielding but drought-susceptible) and Aday Sel
      (drought-tolerant) rice cultivars yielded a stable line with enhanced grain yield
      under drought screening field trials at International Rice Research Institute.
      The major effect qDTY4.1 drought tolerance and yield QTL was detected in the
      IR77298-14-1-2-10 Backcrossed Inbred Line (BIL) and its IR87705-7-15-B Near
      Isogenic Line (NIL) with 93.9% genetic similarity to IR64. Although rice yield is
      extremely susceptible to water stress at reproductive stage, currently, there is
      only one report on the detection of drought-responsive microRNAs in inflorescence
      tissue of a Japonica rice line. In this study, more drought-responsive microRNAs
      were identified in the inflorescence tissues of IR64, IR77298-14-1-2-10 and
      IR87705-7-15-B via next-generation sequencing. Among the 32 families of
      inflorescence-specific non-conserved microRNAs that were identified, 22 families
      were up-regulated in IR87705-7-15-B. Overall 9 conserved and 34 non-conserved
      microRNA families were found as drought-responsive in rice inflorescence with 5
      conserved and 30 non-conserved families induced in the IR87705-7-15-B. The
      observation of more drought-responsive non-conserved microRNAs may imply their
      prominence over conserved microRNAs in drought response mechanisms of rice
      inflorescence. Gene Ontology annotation analysis on the target genes of drought
      responsive microRNAs identified in IR87705-7-15-B revealed over-representation of
      biological processes including development, signalling and response to stimulus.
      Particularly, four inflorescence-specific microRNAs viz. osa-miR5485, osa
      miR5487, osa-miR5492 and osa-miR5517, and two non-inflorescence specific
      microRNAs viz. osa-miR169d and osa-miR169f.2 target genes that are involved in
      flower or embryonic development. Among them, osa-miR169d, osa-miR5492 and osa
      miR5517 are related to flowering time control. It is also worth mentioning that
      osa-miR2118 and osa-miR2275, which are implicated in the biosynthesis of rice
      inflorescence-specific small interfering RNAs, were induced in IR87705-7-15-B but
      repressed in IR77298-14-1-2-10. Further, gene search within qDTY4.1 QTL region
      had identified multiple copies of NBS-LRR resistance genes (potential target of
      osa-miR2118), subtilisins and genes implicated in stomatal movement, ABA
      metabolism and cuticular wax biosynthesis.

PMID- 29045474
TI  - Effects of a non-cyclodextrin cyclic carbohydrate on mouse melanoma cells:
      Characterization of a new type of hypopigmenting sugar.
AB  - Cyclic nigerosyl nigerose (CNN) is a cyclic tetrasaccharide that exhibits
      properties distinct from other conventional cyclodextrins. Herein, we demonstrate
      that treatment of B16 melanoma with CNN results in a dose-dependent decrease in
      melanin synthesis, even under conditions that stimulate melanin synthesis,
      without significant cytotoxity. The effects of CNN were prolonged for more than
      27 days, and were gradually reversed following removal of CNN. Undigested CNN was
      found to accumulate within B16 cells at relatively high levels. Further, CNN
      showed a weak but significant direct inhibitory effect on the enzymatic activity
      of tyrosinase, suggesting one possible mechanism of hypopigmentation. While a
      slight reduction in tyrosinase expression was observed, tyrosinase expression was
      maintained at significant levels, processed into a mature form, and transported
      to late-stage melanosomes. Immunocytochemical analysis demonstrated that CNN
      treatment induced drastic morphological changes of Pmel17-positive and LAMP-1
      positive organelles within B16 cells, suggesting that CNN is a potent organelle
      modulator. Colocalization of both tyrosinase-positive and LAMP-1-positive regions
      in CNN-treated cells indicated possible degradation of tyrosinase in LAMP-1
      positive organelles; however, that possibility was ruled out by subsequent
      inhibition experiments. Taken together, this study opens a new paradigm of
      functional oligosaccharides, and offers CNN as a novel hypopigmenting molecule
      and organelle modulator.

PMID- 29045476
TI  - Spread of domestic animals across Neolithic western Anatolia: New
      zooarchaeological evidence from Ugurlu Hoyuk, the island of Gokceada, Turkey.
AB  - The zooarchaeological research presented here investigates Neolithic and
      Chalcolithic (ca. 6500-5000 cal. BC) animal exploitation strategies at Ugurlu
      Hoyuk on the Turkish island of Gokceada in the northeastern Aegean Sea. Toward
      this end, we first discuss the results of our analysis of the zooarchaeological
      assemblages from Ugurlu Hoyuk and then consider the data within a wider regional
      explanatory framework using a diachronic approach, comparing them with those from
      western and northwestern Anatolian sites. The first settlers of Gokceada were
      farmers who introduced domestic sheep, goats, cattle and pigs to the island as
      early as 6500 years BC. Our results align well with recently published
      zooarchaeological data on the westward spread of domestic animals across Turkey
      and the Neolithization of southeast Europe. Using an island site as a case study,
      we independently confirm that the dispersal of early farming was a polynucleated
      and multidirectional phenomenon that did not sweep across the land, replace
      everything on its way, and deliver the same "Neolithic package" everywhere.
      Instead, this complex process generated a diversity of human-animal interactions.
      Thus, studying the dispersal of early farmers from southwest Asia into southeast
      Europe via Anatolia requires a rigorous methodological approach to develop a fine
      resolution picture of the variability seen in human adaptations and dispersals
      within complex and rapidly changing environmental and cultural settings. For
      this, the whole spectrum of human-animal interactions must be fully documented
      for each sub-region of southwest Asia and the circum-Mediterranean.

PMID- 29045475
TI  - Association between RNA-binding protein Ptbp2 and germ cell injury in an
      experimentally-induced unilateral cryptorchidism murine model.
AB  - RNA binding protein polypyrimidine tract binding protein 2 (Ptbp2) as a key
      alternative splicing regulator for male germ cell development is well
      established. However, its expression levels and role in cryptorchidism testes
      tissues has not been explored. Additionally, the molecular mechanism of heat
      stress impacts the correct proliferation and differentiation of germ cells is
      unclear. To investigate whether changes in Ptbp2 expression are correlated with
      heat stress-induced germ cell injury in testicular tissue, we used a murine model
      of intraperitoneal cryptorchidism with surgical operation. Here we present
      compelling evidence that germ cells are severely damaged in mice with unilateral
      cryptorchidism, with non-obstructive azoospermia. And the Ptbp2 and Pgk2 mRNA
      levels were significantly decreased in parallel, leading us to conclude that the
      negative correlation between Ptbp2 levels and germ cell injury in unilateral
      cryptorchidism murine model. We hypothesize that Ptbp2 is susceptible to heat
      stress and its disruption has resulted in stability decline of germ cell
      transcripts Pgk2 mRNA, which consequently lead to germ cell injury in
      cryptorchidism testes. Thus, we confirm that Ptbp2 is an essential factor in heat
      stress-induced sperm cell injury and non-obstructive azoospermia.

PMID- 29045478
TI  - Camera trap placement and the potential for bias due to trails and other
      features.
AB  - Camera trapping has become an increasingly widespread tool for wildlife
      ecologists, with large numbers of studies relying on photo capture rates or
      presence/absence information. It is increasingly clear that camera placement can
      directly impact this kind of data, yet these biases are poorly understood. We
      used a paired camera design to investigate the effect of small-scale habitat
      features on species richness estimates, and capture rate and detection
      probability of several mammal species in the Shenandoah Valley of Virginia, USA.
      Cameras were deployed at either log features or on game trails with a paired
      camera at a nearby random location. Overall capture rates were significantly
      higher at trail and log cameras compared to their paired random cameras, and some
      species showed capture rates as much as 9.7 times greater at feature-based
      cameras. We recorded more species at both log (17) and trail features (15) than
      at their paired control cameras (13 and 12 species, respectively), yet richness
      estimates were indistinguishable after 659 and 385 camera nights of survey
      effort, respectively. We detected significant increases (ranging from 11-33%) in
      detection probability for five species resulting from the presence of game
      trails. For six species detection probability was also influenced by the presence
      of a log feature. This bias was most pronounced for the three rodents
      investigated, where in all cases detection probability was substantially higher
      (24.9-38.2%) at log cameras. Our results indicate that small-scale factors,
      including the presence of game trails and other features, can have significant
      impacts on species detection when camera traps are employed. Significant biases
      may result if the presence and quality of these features are not documented and
      either incorporated into analytical procedures, or controlled for in study
      design.

PMID- 29045477
TI  - Tubastatin ameliorates pulmonary fibrosis by targeting the TGFbeta-PI3K-Akt
      pathway.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and
      fatal disease. Histone deacetylase 6 (HDAC6) alters function and fate of various
      proteins via deacetylation of lysine residues, and is implicated in TGF-beta1
      induced EMT (epithelial-mesenchymal transition). However, the role of HDAC6 in
      pulmonary fibrosis is unknown. METHODS: HDAC6 expression in IPF and control lungs
      was assessed by quantitative real-time PCR (qRT-PCR) and immunoblots. Lung
      fibroblasts were treated with TGF-beta1 +/- HDAC6 inhibitors (Tubacin,
      Tubastatin, ACY1215, or MC1568), and fibrotic markers such as type I collagen
      were assessed using qRT-PCR and immunoblots. Mice were treated with bleomycin
      (oropharyngeal aspiration; single dose) +/- Tubastatin (intraperitoneally
      injection; daily for 21 days), and lung collagen expression was gauged using
      immunoblots and trichrome staining. In a separate experiment, HDAC6 wild-type
      (WT) and knockout (KO) mice were administered bleomycin, and lungs were evaluated
      in the same manner. RESULTS: HDAC6 expression was deregulated in IPF lungs. Among
      the HDAC6 inhibitors tested, only Tubastatin significantly repressed TGF-beta1
      induced expression of type-1 collagen in lung fibroblasts, and this finding was
      coupled with decreased Akt phosphorylation and increased Akt-PHLPP (PH domain and
      Leucine rich repeat Protein Phosphatase) association. Tubastatin repressed TGF
      beta1-induced S6K phosphorylation, HIF-1alpha expression, and VEGF expression.
      Tubastatin also repressed TGF-beta1-induced inhibition of LC3B-II (a marker of
      autophagosome formation). In bleomycin-treated mouse lungs, HDAC6 expression was
      increased, and Tubastatin repressed type-1 collagen expression. However, in HDAC6
      KO mice, bleomycin-induced type-1 collagen expression was not repressed compared
      to WT mice. Knockdown of HDAC6, as well as HDAC10, another potential Tubastatin
      target, did not inhibit TGF-beta1-induced collagen expression in lung
      fibroblasts. CONCLUSIONS: HDAC6 expression is altered during lung fibrogenesis.
      Tubastatin represses TGF-beta1-induced collagen expression, by diminishing Akt
      phosphorylation and regulating downstream targets such as HIF-1alpha-VEGF axis
      and autophagy. Tubastatin-treated WT mice are protected against bleomycin-induced
      fibrosis, but HDAC6 KO mice are not. Our data suggest that Tubastatin ameliorates
      pulmonary fibrosis, by targeting the TGFbeta-PI3K-Akt pathway, likely via an
      HDAC6-independent mechanism.

PMID- 29045479
TI  - Perception of climate change in patients with chronic lung disease.
AB  - BACKGROUND: Climate change affects human health. The respective consequences are
      predicted to increase in the future. Patients with chronic lung disease are
      particularly vulnerable to the involved environmental alterations. However, their
      subjective perception and reactions to these alterations remain unknown. METHODS:
      In this pilot study, we surveyed 172 adult patients who underwent pulmonary
      rehabilitation and 832 adult tourists without lung disease in the alpine region
      about their perception of being affected by climate change and their potential
      reaction to specific consequences. The patients' survey also contained the COPD
      Assessment Test (CAT) to rate the severity of symptoms. RESULTS: Most of the
      patients stated asthma (73.8%), COPD (9.3%) or both (11.0%) as underlying disease
      while 5.8% suffered from other chronic lung diseases. Patients and tourists feel
      equally affected by current climate change in general, while allergic subjects in
      both groups feel significantly more affected (p = 0.04). The severity of symptoms
      assessed by CAT correlates with the degree of feeling affected (p<0.01). The main
      disturbing consequences for patients are decreased air quality, increasing
      numbers of ticks and mosquitos and a rising risk for allergy and extreme weather
      events such as thunderstroms, while tourists are less disturbed by these factors.
      Increasing number of heat-days is of little concern to both groups. CONCLUSION:
      Overall patients are more sensitive to health-related consequences of climate
      change. Yet, the hazard of heat-days seems underestimated and awareness should be
      raised.

PMID- 29045480
TI  - Quantitative assessment of finger motor performance: Normative data.
AB  - BACKGROUND: Finger opposition movements are the basis of many daily living
      activities and are essential in general for manipulating objects; an engineered
      glove quantitatively assessing motor performance during sequences of finger
      opposition movements has been shown to be useful to provide reliable measures of
      finger motor impairment, even subtle, in subjects affected by neurological
      diseases. However, the obtained behavioral parameters lack published reference
      values. OBJECTIVE: To determine mean values for different motor behavioral
      parameters describing the strategy adopted by healthy people in performing
      repeated sequences of finger opposition movements, examining associations with
      gender and age. METHODS: Normative values for finger motor performance parameters
      were obtained on a sample of 255 healthy volunteers executing sequences of finger
      to-thumb opposition movements, stratified by gender and over a wide range of
      ages. Touch duration, inter-tapping interval, movement rate, correct sequences
      (%), movements in advance compared with a metronome (%) and inter-hand interval
      were assessed. RESULTS: Increasing age resulted in decreased movement speed,
      advance movements with respect to a cue, correctness of sequences, and bimanual
      coordination. No significant performance differences were found between male and
      female subjects except for the duration of the finger touch, the interval between
      two successive touches and their ratio. CONCLUSIONS: We report age- and gender
      specific normal mean values and ranges for different parameters objectively
      describing the performance of finger opposition movement sequences, which may
      serve as useful references for clinicians to identify possible deficits in
      subjects affected by diseases altering fine hand motor skills.

PMID- 29045481
TI  - The effect of growth phase on the surface properties of three oleaginous
      microalgae (Botryococcus sp. FACGB-762, Chlorella sp. XJ-445 and Desmodesmus
      bijugatus XJ-231).
AB  - The effects of growth phase on the lipid content and surface properties of
      oleaginous microalgae Botryococcus sp. FACGB-762, Chlorella sp. XJ-445 and
      Desmodesmus bijugatus XJ-231 were investigated in this study. The results showed
      that throughout the growth phases, the lipid content of microalgae increased. The
      surface properties like particle size, the degree of hydrophobicity, and the
      total concentration of functional groups increased while net surface zeta
      potential decreased. The results suggested that the growth stage had significant
      influence not only on the lipid content but also on the surface characteristics.
      Moreover, the lipid content was significantly positively related to the
      concentration of hydroxyl functional groups in spite of algal strains or growth
      phases. These results provided a basis for further studies on the refinery
      process using oleaginous microalgae for biofuel production.

PMID- 29045482
TI  - Influence on number of top-ups after implementing patient controlled epidural
      analgesia: A cohort study.
AB  - Postoperative epidural analgesia often needs rate readjustment using top-ups.
      Patient-controlled epidural analgesia (PCEA) is said to reduce the requirement of
      epidural top-ups when compared to continuous epidural analgesia (CEA). We
      compared CEA and PCEA in major thoracic and abdominal surgery, in a cohort study.
      The primary endpoint was the required number of epidural top-ups. Secondary
      endpoints were pain scores, side effects and workload differences. We analysed
      199 patients with CEA and 187 with PCEA. Both groups had similar pain scores. The
      total number of top-ups was 75 in 57 patients (CEA) versus 20 top-ups in 18
      patients (PCEA). (p = 0.0001) Sedation tended to occur more frequently in
      patients with CEA versus PCEA, 5.5% vs 1.6% (p = 0.05). Implementation of PCEA
      led to a decreased number of top-ups, fewer side-effects and decreased use of the
      postoperative care unit.

PMID- 29045484
TI  - Semi-field assessment of the BG-Malaria trap for monitoring the African malaria
      vector, Anopheles arabiensis.
AB  - Odour-baited technologies are increasingly considered for effective monitoring of
      mosquito populations and for the evaluation of vector control interventions. The
      BG-Malaria trap (BGM), which is an upside-down variant of the widely used BG
      Sentinel trap (BGS), has been demonstrated to be effective to sample the
      Brazilian malaria vector, Anopheles darlingi. We evaluated the BGM as an improved
      method for sampling the African malaria vectors, Anopheles arabiensis.
      Experiments were conducted inside a large semi-field cage to compare trapping
      efficiencies of BGM and BGS traps, both baited with the synthetic attractant,
      Ifakara blend, supplemented with CO2. We then compared BGMs baited with either of
      four synthetic mosquito lures, Ifakara blend, Mbita blend, BG-lure or CO2, and an
      unbaited BGM. Lastly, we compared BGMs baited with the Ifakara blend dispensed
      via either nylon strips, BG cartridges (attractant-infused microcapsules encased
      in cylindrical plastic cartridge) or BG sachets (attractant-infused microcapsules
      encased in plastic sachets). All tests were conducted between 6P.M. and 7A.M.,
      with 200-600 laboratory-reared An. arabiensis released nightly in the test
      chamber. The median number of An. arabiensis caught by the BGM per night was 83,
      IQR:(73.5-97.75), demonstrating clear superiority over BGS (median catch = 32.5
      (25.25-37.5)). Compared to unbaited controls, BGMs baited with Mbita blend caught
      most mosquitoes (45 (29.5-70.25)), followed by BGMs baited with CO2 (42.5 (27.5
      64)), Ifakara blend (31 (9.25-41.25)) and BG lure (16 (4-22)). BGM caught 51
      (29.5-72.25) mosquitoes/night, when the attractants were dispensed using BG
      Cartridges, compared to BG-Sachet (29.5 (24.75-40.5)), and nylon strips (27
      (19.25-38.25)), in all cases being significantly superior to unbaited controls (p
      < 000.1). The findings demonstrate potential of the BGM as a sampling tool for
      African malaria vectors over the standard BGS trap. Its efficacy can be optimized
      by selecting appropriate odour baits and odour-dispensing systems.

PMID- 29045483
TI  - Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk
      population: The ESCARVAL-RISK study.
AB  - INTRODUCTION: The potential impact of targeting different components of an
      adverse lipid profile in populations with multiple cardiovascular risk factors is
      not completely clear. This study aims to assess the association between different
      components of the standard lipid profile with all-cause mortality and
      hospitalization due to cardiovascular events in a high-risk population. METHODS:
      This prospective registry included high risk adults over 30 years old free of
      cardiovascular disease (2008-2012). Diagnosis of hypertension, dyslipidemia or
      diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated.
      Primary endpoints were all-cause mortality and hospital admission due to coronary
      heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk
      differences and population attributable risk associated with adverse lipid
      profiles. RESULTS: 51,462 subjects were included with a mean age of 62.6 years
      (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666
      hospitalizations for coronary heart disease and 1510 hospitalizations for stroke
      were recorded. The parameters that showed an increased rate for total mortality,
      coronary heart disease and stroke hospitalization were, respectively, low HDL
      Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38
      and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The
      parameters that showed highest population attributable risk (%) were,
      respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol:
      6.55, 12.47, 8.73; and high Triglycerides/HDL-Cholesterol: 8.94, 15.09, 6.92.
      CONCLUSIONS: In a population with cardiovascular risk factors, HDL-cholesterol,
      Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated
      with a higher population attributable risk for cardiovascular disease compared to
      other common biomarkers.

PMID- 29045485
TI  - Alterations in the placental methylome with maternal obesity and evidence for
      metabolic regulation.
AB  - The inflammatory and metabolic derangements of obesity in pregnant women generate
      an adverse intrauterine environment, increase pregnancy complications and adverse
      fetal outcomes and program the fetus for obesity and metabolic syndrome in later
      life. We hypothesized that epigenetic modifications in placenta including altered
      DNA methylation/hydroxymethylation may mediate these effects. Term placental
      villous tissue was collected following cesarean section from lean (prepregnancy
      BMI<25) or obese (BMI>30) women. Genomic DNA was isolated, methylated and
      hydroxymethylated DNA immunoprecipitated and hybridized to the NimbleGen 2.1M
      human DNA methylation array. Intermediate metabolites in placental tissues were
      measured by HPLC-ESI-MS, ascorbate levels by reverse phase HPLC and gene
      expression by RT-PCR. Differentially methylated and hydroxymethylated regions
      occurred across the genome, with a 21% increase in methylated but a 31% decrease
      in hydroxymethylated regions in obese vs lean groups. Whereas increased
      methylation and decreased methylation was evident around transcription start
      sites of multiple genes in the GH/CSH and PSG gene clusters on chromosomes 17 and
      19 in other areas there was no relationship. Increased methylation was associated
      with decreased expression only for some genes in these clusters. Biological
      pathway analysis revealed the 262 genes which showed reciprocal differential
      methylation/ hydroxymethylation were enriched for pregnancy, immune response and
      cell adhesion-linked processes. We found a negative relationship for maternal BMI
      but a positive relationship for ascorbate with alpha-ketoglutarate a metabolite
      that regulates ten eleven translocase (TET) which mediates DNA methylation. We
      provide evidence for the obese maternal metabolic milieu being linked to an
      altered DNA methylome that may affect placental gene expression in relation to
      adverse outcomes.

PMID- 29045487
TI  - The psychosocial impact of leg ulcers in patients with sickle cell disease: I
      don't want them to know my little secret.
AB  - BACKGROUND: Sickle cell disease (SCD) impacts millions of individuals worldwide
      and more than 100,000 people in the United States. Leg ulcers are the most common
      cutaneous manifestation of SCD. The health status of individuals living with
      chronic leg ulcers is not only influenced by clinical manifestations such as pain
      duration and intensity, but also by psychosocial factors. Garnering insights into
      the psychosocial impact can provide a more holistic view of their influence on
      quality of life. METHODS: Semi-structured interviews were conducted with
      participants living with active SCD-associated leg ulcers or with a history of
      ulcers. Subjects were recruited from an ongoing study (INSIGHTS, Clin Trial.Gov
      NCT02156102) and consented to this qualitative phase of the study. Five areas
      were explored: leg ulcer pain, physical function, social-isolation, social
      relationships and religious support. Data was collected from 20 individuals
      during these interviews and a thematic analysis was performed and reported.
      RESULTS: Twenty participants with a mean age of 42.4 (SD +/- 11.1years) were
      included in the study. Major themes identified included:1) pain (acute and
      chronic); 2) compromised physical function as demonstrated by decreased ability
      to walk, run, and play sports; 3) social isolation from activities either by
      others or self-induced as a means of avoiding certain emotions, such as
      embarrassment; 4) social relationships (family support and social network); 5)
      support and comfort through their religion or spirituality. CONCLUSIONS: SCD
      patients with leg ulcers expressed that they experience social isolation, intense
      and frequent ulcer pain, and difficulty in physical function. SCD-associated leg
      ulcers have been studied from a clinical approach, but the psychosocial factors
      investigated in this study informs how quality of life is impacted by the leg
      ulcers.

PMID- 29045488
TI  - Alseodaphnopsis: A new genus of Lauraceae based on molecular and morphological
      evidence.
AB  - An investigation of a questionable species of the genus Alseodaphne led to the
      discovery of a new genus Alseodaphnopsis H. W. Li & J. Li, gen. nov., separated
      from Alseodaphne Nees, and a new species Alseodaphnopsis ximengensis H. W. Li &
      J. Li, sp. nov., endemic to Yunnan province, China. This new species is
      characterized by having big, axillary, paniculate inflorescences, as well as
      large, subglobose fruits. Based on DNA sequence data from two gene regions
      (nuclear ribosomal ITS and LEAFY intron II), we investigate its phylogenetic
      position within the Persea group. Phylogenies using maximum parsimony (MP) and
      Bayesian inference (BI) support the recognition of Alseodaphnopsis as a distinct
      genus but do not resolve well its relationship within the Persea group. The new
      genus is circumscribed, eight new combinations for its species are made, and a
      description and illustration of the new species are provided.

PMID- 29045486
TI  - Thiamine deficiency activates hypoxia inducible factor-1alpha to facilitate pro
      apoptotic responses in mouse primary astrocytes.
AB  - Thiamine is an essential enzyme cofactor required for proper metabolic function
      and maintenance of metabolism and energy production in the brain. In developed
      countries, thiamine deficiency (TD) is most often manifested following chronic
      alcohol consumption leading to impaired mitochondrial function, oxidative stress,
      inflammation and excitotoxicity. These biochemical lesions result in apoptotic
      cell death in both neurons and astrocytes. Comparable histological injuries in
      patients with hypoxia/ischemia and TD have been described in the thalamus and
      mammillary bodies, suggesting a congruency between the cellular responses to
      these stresses. Consistent with hypoxia/ischemia, TD stabilizes and activates
      Hypoxia Inducible Factor-1alpha (HIF-1alpha) under physiological oxygen levels.
      However, the role of TD-induced HIF-1alpha in neurological injury is currently
      unknown. Using Western blot analysis and RT-PCR, we have demonstrated that TD
      induces HIF-1alpha expression and activity in primary mouse astrocytes. We
      observed a time-dependent increase in mRNA and protein expression of the pro
      apoptotic and pro-inflammatory HIF-1alpha target genes MCP1, BNIP3, Nix and Noxa
      during TD. We also observed apoptotic cell death in TD as demonstrated by
      PI/Annexin V staining, TUNEL assay, and Cell Death ELISA. Pharmacological
      inhibition of HIF-1alpha activity using YC1 and thiamine repletion both reduced
      expression of pro-apoptotic HIF-1alpha target genes and apoptotic cell death in
      TD. These results demonstrate that induction of HIF-1alpha mediated
      transcriptional up-regulation of pro-apoptotic/inflammatory signaling contributes
      to astrocyte cell death during thiamine deficiency.

PMID- 29045489
TI  - Ciguatoxicity of Gambierdiscus and Fukuyoa species from the Caribbean and Gulf of
      Mexico.
AB  - Dinoflagellate species belonging to the genera Gambierdiscus and Fukuyoa produce
      ciguatoxins (CTXs), potent neurotoxins that concentrate in fish causing ciguatera
      fish poisoning (CFP) in humans. While the structures and toxicities of
      ciguatoxins isolated from fish in the Pacific and Caribbean are known, there are
      few data on the variation in toxicity between and among species of Gambierdiscus
      and Fukuyoa. Quantifying the differences in species-specific toxicity is
      especially important to developing an effective cell-based risk assessment
      strategy for CFP. This study analyzed the ciguatoxicity of 33 strains
      representing seven Gambierdiscus and one Fukuyoa species using a cell based Neuro
      2a cytotoxicity assay. All strains were isolated from either the Caribbean or
      Gulf of Mexico. The average toxicity of each species was inversely proportional
      to growth rate, suggesting an evolutionary trade-off between an investment in
      growth versus the production of defensive compounds. While there is 2- to 27-fold
      variation in toxicity within species, there was a 1740-fold difference between
      the least and most toxic species. Consequently, production of CTX or CTX-like
      compounds is more dependent on the species present than on the random occurrence
      of high or low toxicity strains. Seven of the eight species tested (G.
      belizeanus, G. caribaeus, G. carolinianus, G. carpenteri, Gambierdiscus ribotype
      2, G. silvae and F. ruetzleri) exhibited low toxicities, ranging from 0 to 24.5
      fg CTX3C equivalents cell-1, relative to G. excentricus, which had a toxicity of
      469 fg CTX3C eq. cell-1. Isolates of G. excentricus from other regions have shown
      similarly high toxicities. If the hypothesis that G. excentricus is the primary
      source of ciguatoxins in the Atlantic is confirmed, it should be possible to
      identify areas where CFP risk is greatest by monitoring only G. excentricus
      abundance using species-specific molecular assays.

PMID- 29045490
TI  - The ethylene response factor AtERF4 negatively regulates the iron deficiency
      response in Arabidopsis thaliana.
AB  - Iron (Fe) deficiency is one of many conditions that can seriously damage crops.
      Low levels of photosynthesis can lead to the degradation of chlorophyll content
      and impaired respiration in affected plants, which together cause poor growth and
      reduce quality. Although ethylene plays an important role in responses to Fe
      deficiency, a limited number of studies have been carried out on ethylene
      response factor (ERFs) as components of plant regulation mechanisms. Thus, this
      study aimed to investigate the role of AtERF4 in plant responses to Fe
      deficiency. Results collected when Arabidopsis thaliana was grown under Fe
      deficient conditions as well as in the presence of 1-aminocyclopropane-1
      carboxylic acid (ACC) revealed that leaf chlorosis did not occur over short
      timescales and that chloroplast structural integrity was retained. At the same
      time, expression of the chlorophyll degradation-related genes AtPAO and AtCLH1
      was inhibited and net H+ root flux was amplified. Our results show that
      chlorophyll content was enhanced in the mutant erf4, while expression of the
      chlorophyll degradation gene AtCLH1 was reduced. Ferric reductase activity in
      roots was also significantly higher in the mutant than in wild type plants, while
      erf4 caused high levels of expression of the genes AtIRT1 and AtHA2 under Fe
      deficient conditions. We also utilized yeast one-hybrid technology in this study
      to determine that AtERF4 binds directly to the AtCLH1 and AtITR1 promoter.
      Observations show that transient over-expression of AtERF4 resulted in rapid
      chlorophyll degradation in the leaves of Nicotiana tabacum and the up-regulation
      of gene AtCLH1 expression. In summary, AtERF4 plays an important role as a
      negative regulator of Fe deficiency responses, we hypothesize that AtERF4 may
      exert a balancing effect on plants subject to nutrition stress.

PMID- 29045491
TI  - Monte Carlo simulation of secondary neutron dose for scanning proton therapy
      using FLUKA.
AB  - Proton therapy is a rapidly progressing field for cancer treatment. Globally,
      many proton therapy facilities are being commissioned or under construction.
      Secondary neutrons are an important issue during the commissioning process of a
      proton therapy facility. The purpose of this study is to model and validate
      scanning nozzles of proton therapy at Samsung Medical Center (SMC) by Monte Carlo
      simulation for beam commissioning. After the commissioning, a secondary neutron
      ambient dose from proton scanning nozzle (Gantry 1) was simulated and measured.
      This simulation was performed to evaluate beam properties such as percent depth
      dose curve, Bragg peak, and distal fall-off, so that they could be verified with
      measured data. Using the validated beam nozzle, the secondary neutron ambient
      dose was simulated and then compared with the measured ambient dose from Gantry
      1. We calculated secondary neutron dose at several different points. We
      demonstrated the validity modeling a proton scanning nozzle system to evaluate
      various parameters using FLUKA. The measured secondary neutron ambient dose
      showed a similar tendency with the simulation result. This work will increase the
      knowledge necessary for the development of radiation safety technology in medical
      particle accelerators.

PMID- 29045492
TI  - Multitasking in older adults with type 2 diabetes: A cross-sectional analysis.
AB  - BACKGROUND AND PURPOSE: Deficits in the ability to multitask contribute to gait
      abnormalities and falls in many at-risk populations. However, it is unclear
      whether older adults with type 2 diabetes mellitus (DM) also demonstrate
      impairments in multitasking. The purpose of this study was to compare
      multitasking performance in cognitively intact older adults with and without DM
      and explore its relationship to measures of gait and functional ability. METHODS:
      We performed a cross-sectional analysis of 40 individuals aged 60 and older with
      type 2 DM and a matched group of 40 cognitively intact older adults without DM.
      Multitasking was examined via the ambulatory Walking and Remembering Test (WART)
      and seated Pursuit Rotor Test (PRT). Self-selected normal and fast walking speed
      and stride length variability were quantitatively measured, and self-reported
      functional ability was assessed via the Late Life Function and Disability Index
      (LLFDI). RESULTS: Participants with DM walked slower and took more steps off path
      when multitasking during the WART. No between-group differences in multitasking
      performance were observed on the PRT. Multitasking performance demonstrated
      little correlation with gait and functional ability in either group. DISCUSSION
      AND CONCLUSIONS: Older adults with DM appear to perform poorly on an ambulatory
      measure of multitasking. However, we analyzed a relatively small, homogenous
      sample of older adults with and without type 2 DM and factors such as peripheral
      neuropathy and the use of multiple comparisons complicate interpretation of the
      data. Future research should explore the interactions between multitasking and
      safety, fall risk, and function in this vulnerable population. Clinicians should
      recognize that an array of factors may contribute to gait and physical
      dysfunction in older adults with type 2 diabetes, and be prepared to assess and
      intervene appropriately.

PMID- 29045493
TI  - The sequence preference of DNA methylation variation in mammalians.
AB  - Methylation of cytosine at the 5 position of the pyrimidine ring is the most
      prevalent and significant epigenetic modifications in mammalian DNA. The CpG
      methylation level shows a bimodal distribution but the bimodality can be
      overestimated due to the heterogeneity of per-base depth. Here, we developed an
      algorithm to eliminate the effect of per-base depth inhomogeneity on the
      bimodality and obtained a random CpG methylation distribution. By quantifying the
      deviation of the observed methylation distribution and the random one using the
      information formula, we find that in tetranucleotides 5'-N5CGN3-3' (N5, N3 = A,
      C, G or T), GCGN3 and CCGN3 show less apparent deviation than ACGN3 and TCGN3,
      indicating that GCGN3 and CCGN3 are less variant in their level of methylation.
      The methylation variation of N5CGN3 are conserved among different cells, tissues
      and species, implying common features in the mechanisms of methylation and
      demethylation, presumably mediated by DNMTs and TETs in mammalians, respectively.
      Sequence dependence of DNA methylation variation also relates to gene regulatory
      and promotes the reexamination of the role of DNA sequence in fundamental
      biological processes.

PMID- 29045494
TI  - Results of a massive experiment on virtual currency endowments and money demand.
AB  - We use a 575,000-subject, 28-day experiment to investigate monetary policy in a
      virtual setting. The experiment tests the effect of virtual currency endowments
      on player retention and virtual currency demand. An increase in endowments of a
      virtual currency should lower the demand for the currency in the short run.
      However, in the long run, we would expect money demand to rise in response to
      inflation in the virtual world. We test for this behavior in a virtual field
      experiment in the football management game Top11. 575,000 players were selected
      at random and allocated to different "shards" or versions of the world. The
      shards differed only in terms of the initial money endowment offered to new
      players. Money demand was observed for 28 days as players used real money to
      purchase additional virtual currency. The results indicate that player money
      purchases were significantly higher in the shards where higher endowments were
      given. This suggests that a positive change in the money supply in a virtual
      context leads to inflation and increased money demand, and does so much more
      quickly than in real-world economies. Differences between virtual and real
      currency behavior will become more interesting as virtual currency becomes a
      bigger part of the real economy.

PMID- 29045495
TI  - Correction: PD-1 Blockade and OX40 Triggering Synergistically Protects against
      Tumor Growth in a Murine Model of Ovarian Cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0089350.].

PMID- 29045496
TI  - At same leucine intake, a whey/plant protein blend is not as effective as whey to
      initiate a transient post prandial muscle anabolic response during a catabolic
      state in mini pigs.
AB  - BACKGROUND: Muscle atrophy has been explained by an anabolic resistance following
      food intake and an increase of dietary protein intake is recommended. To be
      optimal, a dietary protein has to be effective not only to initiate but also to
      prolong a muscle anabolic response in a catabolic state. To our knowledge,
      whether or not a dairy or a dairy/plant protein blend fulfills these criterions
      is unknown in a muscle wasting situation. OBJECTIVE: Our aim was, in a control
      and a catabolic state, to measure continuously muscle anabolism in term of
      intensity and duration in response to a meal containing casein (CAS), whey (WHEY)
      or a whey/ plant protein blend (BLEND) and to evaluate the best protein source to
      elicit the best post prandial anabolism according to the physio-pathological
      state. METHODS: Adult male Yucatan mini pigs were infused with U-13C
      Phenylalanine and fed either CAS, WHEY or BLEND. A catabolic state was induced by
      a glucocorticoid treatment for 8 days (DEX). Muscle protein synthesis,
      proteolysis and balance were measured with the hind limb arterio-venous
      differences technique. Repeated time variance analysis were used to assess
      significant differences. RESULTS: In a catabolic situation, whey proteins were
      able to initiate muscle anabolism which remained transient in contrast to the
      stimulated muscle protein accretion with WHEY, CAS or BLEND in healthy
      conditions. Despite the same leucine intake compared to WHEY, BLEND did not
      restore a positive protein balance in DEX animals. CONCLUSIONS: Even with WHEY,
      the duration of the anabolic response was not optimal and has to be improved in a
      catabolic state. The use of BLEND remained of lower efficiency even at same
      leucine intake than whey.

PMID- 29045497
TI  - Ceftriaxone- and N-acetylcysteine-induced brain tolerance to ischemia: Influence
      on glutamate levels in focal cerebral ischemia.
AB  - One of the major players in the pathophysiology of cerebral ischemia is disrupted
      homeostasis of glutamatergic neurotransmission, resulting in elevated
      extracellular glutamate (Glu) concentrations and excitotoxicity-related cell
      death. In the brain, Glu concentrations are regulated by Glu transporters,
      including Glu transporter-1 (GLT-1) and cystine/Glu antiporter (system xc-).
      Modulation of these transporters by administration of ceftriaxone (CEF, 200
      mg/kg, i.p.) or N-acetylcysteine (NAC, 150 mg/kg, i.p.) for 5 days before focal
      cerebral ischemia may induce brain tolerance to ischemia by significantly
      limiting stroke-related damage and normalizing Glu concentrations. In the present
      study, focal cerebral ischemia was induced by 90-minute middle cerebral artery
      occlusion (MCAO). We compared the effects of CEF and NAC pretreatment on Glu
      concentrations in extracellular fluid and cellular-specific expression of GLT-1
      and xCT with the effects of two reference preconditioning methods, namely,
      ischemic preconditioning and chemical preconditioning in rats. Both CEF and NAC
      significantly reduced Glu levels in the frontal cortex and hippocampus during
      focal cerebral ischemia, and this decrease was comparable with the Glu level
      achieved with the reference preconditioning strategies. The results of
      immunofluorescence staining of GLT-1 and xCT on astrocytes, neurons and microglia
      accounted for the observed changes in extracellular Glu levels to a certain
      extent. Briefly, after MCAO, the expression of GLT-1 on astrocytes decreased, but
      pretreatment with CEF seemed to prevent this downregulation. In addition, every
      intervention used in this study seemed to reduce xCT expression on astrocytes and
      neurons. The results of this study indicate that modulation of Glu transporter
      expression may restore Glu homeostasis. Moreover, our results suggest that CEF
      and NAC may induce brain tolerance to ischemia by influencing GLT-1 and system xc
      expression levels. These transporters are presumably good targets for the
      development of novel therapies for brain ischemia.

PMID- 29045498
TI  - Novel drug targets in cell wall biosynthesis exploited by gene disruption in
      Pseudomonas aeruginosa.
AB  - For clinicians, Pseudomonas aeruginosa is a nightmare pathogen that is one of the
      top three causes of opportunistic human infections. Therapy of P. aeruginosa
      infections is complicated due to its natural high intrinsic resistance to
      antibiotics. Active efflux and decreased uptake of drugs due to cell
      wall/membrane permeability appear to be important issues in the acquired
      antibiotic tolerance mechanisms. Bacterial cell wall biosynthesis enzymes have
      been shown to be essential for pathogenicity of Gram-negative bacteria. However,
      the role of these targets in virulence has not been identified in P. aeruginosa.
      Here, we report knockout (k.o) mutants of six cell wall biosynthesis targets
      (murA, PA4450; murD, PA4414; murF, PA4416; ppiB, PA1793; rmlA, PA5163; waaA,
      PA4988) in P. aeruginosa PAO1, and characterized these in order to find out
      whether these genes and their products contribute to pathogenicity and virulence
      of P. aeruginosa. Except waaA k.o, deletion of cell wall biosynthesis targets
      significantly reduced growth rate in minimal medium compared to the parent
      strain. The k.o mutants showed exciting changes in cell morphology and colonial
      architectures. Remarkably, DeltamurF cells became grossly enlarged. Moreover, the
      mutants were also attenuated in vivo in a mouse infection model except DeltamurF
      and DeltawaaA and proved to be more sensitive to macrophage-mediated killing than
      the wild-type strain. Interestingly, the deletion of the murA gene resulted in
      loss of virulence activity in mice, and the virulence was restored in a plant
      model by unknown mechanism. This study demonstrates that cell wall targets
      contribute significantly to intracellular survival, in vivo growth, and
      pathogenesis of P. aeruginosa. In conclusion, these findings establish a link
      between cell wall targets and virulence of P. aeruginosa and thus may lead to
      development of novel drugs for the treatment of P. aeruginosa infection.

PMID- 29045499
TI  - Obstetric and psychological characteristics of women choosing epidural analgesia
      during labour: A cohort study.
AB  - OBJECTIVES: To investigate the obstetric and psychological characteristics of
      women who opt to use epidural analgesia (EDA) during labour and the impact of
      participating in labour preparation courses on women's decisions to use EDA.
      DESIGN: Longitudinal cohort study. SETTING: Akershus University Hospital, Norway.
      POPULATION: 2596 women with singleton pregnancies and intended vaginal delivery.
      METHODS: Data were collected using two self-completed questionnaires at pregnancy
      weeks 17 and 32. Fear of childbirth was assessed by the Wijma Delivery Expectancy
      Questionnaire (W-DEQ). Symptoms of anxiety were measured by the Hopkins Symptom
      Check List (SCL-25) and depression by the Edinburgh Postnatal Depression Scale
      (EPDS). Obstetric and socio-demographic information was retrieved from birth
      records at the maternity ward. MAIN OUTCOME MEASURE: Preference for EDA was
      indicated by the questionnaire item "I would prefer an epidural regardless" on a
      4-point scale (1 = highly agree, 4 = highly disagree) at pregnancy week 32.
      RESULTS: Twenty-one percent of the women (540/2596) answered that they would
      choose EDA as the only alternative method of analgesia during labour. Counselling
      for fear of childbirth [OR 3.23 (95%CI 2.12; 4.92)] and W-DEQ sum score >= 85 [OR
      2.95 (95%CI 2.06; 4.23)] were significantly (p<0.001) associated with choice of
      EDA. Participation in labour preparation courses was significantly (p = 0.008)
      associated with a reduction of intended use of EDA during labour [OR 0.67 (95%CI
      0.49; 0.90)]. CONCLUSION: Fear of childbirth is significantly associated with
      women's choice of EDA during labour. On the other hand, women that participate in
      labour preparation courses would rather consider other methods of analgesia
      during labour.

PMID- 29045500
TI  - Using egocentric analysis to investigate professional networks and productivity
      of graduate students and faculty in life sciences in Japan, Singapore, and
      Taiwan.
AB  - Prior studies showed that scientists' professional networks contribute to
      research productivity, but little work has examined what factors predict the
      formation of professional networks. This study sought to 1) examine what factors
      predict the formation of international ties between faculty and graduate students
      and 2) identify how these international ties would affect publication
      productivity in three East Asian countries. Face-to-face surveys and in-depth
      semi-structured interviews were conducted with a sample of faculty and doctoral
      students in life sciences at 10 research institutions in Japan, Singapore, and
      Taiwan. Our final sample consisted of 290 respondents (84 faculty and 206
      doctoral students) and 1,435 network members. We used egocentric social network
      analysis to examine the structure of international ties and how they relate to
      research productivity. Our findings suggest that overseas graduate training can
      be a key factor in graduate students' development of international ties in these
      countries. Those with a higher proportion of international ties in their
      professional networks were likely to have published more papers and written more
      manuscripts. For faculty, international ties did not affect the number of
      manuscripts written or of papers published, but did correlate with an increase in
      publishing in top journals. The networks we examined were identified by asking
      study participants with whom they discuss their research. Because the
      relationships may not appear in explicit co-authorship networks, these networks
      were not officially recorded elsewhere. This study sheds light on the
      relationships of these invisible support networks to researcher productivity.

PMID- 29045501
TI  - Scaffold dependent histone deacetylase (HDAC) inhibitor induced re-equilibration
      of the subcellular localization and post-translational modification state of
      class I HDACs.
AB  - The mechanism of action of histone deacetylase inhibitors (HDACi) is mainly
      attributed to the inhibition of the deacetylase catalytic activity for their
      histone substrates. In this study, we analyzed the abundance of class I HDACs in
      the cytosolic, nuclear soluble and chromatin bound cellular fractions in breast
      cancer cells after HDACi treatment. We found that potent N-hydroxy propenamide
      based HDACi induced a concentration dependent decrease in the HDAC1 associated
      with chromatin and a lasting concomitant increase in cytoplasmic HDAC1 while
      maintaining total protein expression. No such change occurred with HDAC2 or 8,
      however, an increase in cytoplasmic non-phosphorylated HDAC3 was also observed.
      The subcellular re-equilibration of HDAC1 was subsequent to the accumulation of
      acetylated histones and might be cell cycle dependent. This study suggests that
      the biological activity of a subset of N-hydroxy propenamide-based HDACi may stem
      from direct competition with histone substrates of HDACs as well as from spatial
      separation from their substrates in the nucleus and/or change in post
      translational modification status of HDACs.

PMID- 29045503
TI  - Maintenance therapy following induction chemoimmunotherapy in patients with
      diffuse large B-cell lymphoma: current perspective.
AB  - Background: Maintenance therapy has proven efficacy in indolent non-Hodgkin
      lymphoma (NHL), yet its role in diffuse large B-cell lymphoma (DLBCL) is an area
      of ongoing investigation. While DLBCL is potentially curable, >30% of patients
      relapse following front-line therapy and have a poor prognosis, especially those
      with refractory disease. Maintenance therapy holds promise to maintain response
      post-induction. Patients and methods: Keyword searches were carried out in PubMed
      and congress abstracts of 'diffuse large B-cell lymphoma' and 'maintenance' and
      focused on phase II/III studies of maintenance following front-line induction.
      Results: Although used in indolent forms of NHL, studies of maintenance therapy
      with rituximab in patients with DLBCL responding to front-line R-CHOP
      (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) have not improved
      efficacy and are not recommended. Targeted agents enzastaurin and everolimus
      reported results from the phase III studies PRELUDE and PILLAR-2, respectively,
      both of which showed no proven maintenance benefit following front-line
      chemoimmunotherapy induction. Overall, the reported efficacy results with these
      agents in the maintenance setting do not outweigh the risks. Lenalidomide for
      maintenance has been reported in three studies. Results from two phase II trials
      on lenalidomide maintenance revealed positive outcomes in higher-risk patients
      following induction, resulting in improved progression-free survival in relapsed
      DLBCL patients who were ineligible for transplantation. First analysis from the
      phase III REMARC trial showed a significant improvement in progression-free
      survival for lenalidomide versus placebo, with no difference in overall survival,
      following front-line R-CHOP induction in elderly patients. Conclusions: Based on
      currently available studies of DLBCL maintenance therapies, initial results in
      front-line, as well as the relapsed setting, with immunomodulators such as
      lenalidomide show promise for further research to identify appropriate patients
      who would most benefit. Overall, this review of maintenance studies underscores
      the need for additional analyses of patient subtypes, clinical risk status, and
      molecular profiles, with careful consideration of study end points.

PMID- 29045504
TI  - Molecular Tumor Boards: current practice and future needs.
AB  - Background: Due to rapid technical advances, steeply declining sequencing costs,
      and the ever-increasing number of targeted therapies, it can be expected that
      extensive tumor sequencing such as whole-exome and whole-genome sequencing will
      soon be applied in standard care. Clinicians will thus be confronted with
      increasingly complex genetic information and multiple test-platforms to choose
      from. General medical training, meanwhile, can hardly keep up with the pace of
      innovation. Consequently, there is a rapidly growing gap between clinical
      knowledge and genetic potential in cancer care. Multidisciplinary Molecular Tumor
      Boards (MTBs) have been suggested as a means to address this disparity, but
      shared experiences are scarce in literature and no quality requirements or
      guidelines have been published to date. Methods: Based on literature review, a
      survey among hospitals in The Netherlands, and our own experience with the
      establishment of a nationally operating MTB, this article evaluates current
      knowledge and unmet needs and lays out a strategy for successful MTB
      implementation. Results: Having access to an MTB can improve and increase the
      application of genetics-guided cancer care. In our survey, however, <50% of
      hospitals and only 5% of nonacademic hospitals had access to an MTB. In addition,
      current MTBs vary widely in terms of composition, tasks, tools, and workflow.
      This may not only lead to variation in quality of care but also hinders data
      sharing and thus creation of an effective learning community. Conclusions: This
      article acknowledges a leading role for MTBs to govern (extensive) tumor
      sequencing into daily practice and proposes three basic necessities for
      successful MTB implementation: (i) global harmonization in cancer sequencing
      practices and procedures, (ii) minimal member and operational requirements, and
      (iii) an appropriate unsolicited findings policy. Meeting these prerequisites
      would not only optimize MTB functioning but also improve general interpretation
      and application of genomics-guided cancer care.

PMID- 29045502
TI  - Long-term toxicity of cisplatin in germ-cell tumor survivors.
AB  - Context: Testicular germ-cell tumors (GCT) are highly curable. A
      multidisciplinary approach, including cisplatin-based chemotherapy has resulted
      in cure in the majority of patients with GCT. Thus, the life expectancy of
      survivors will extend to many decades post-diagnosis. Late treatment toxicities
      associated with cisplatin-based chemotherapy may impact their future health.
      Objective: To systematically evaluate evidence regarding the long-term toxicity
      of cisplatin in GCT survivors. Evidence acquisition: We carried out a critical
      review of PubMed/Medline in February 2017 according to the Preferred Reporting
      Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified
      reports were reviewed according to the Consolidated Standards of Reporting Trials
      (CONSORT) criteria. Eighty-three publications were selected for inclusion in this
      analysis. Evidence synthesis: Included reports evaluated long-term toxicities of
      cisplatin-based chemotherapy in GCT survivors. Studies reporting neuro- and
      ototoxicity, secondary malignancies, cardiovascular, renal and pulmonary
      toxicities, hypogonadism and infertility were found. Seven studies (8%) reported
      genetic underpinnings of long-term toxicities and 3 (4%) and 14 (19%) studies
      correlated long-term toxicities with circulating platinum levels and cumulative
      dose of cisplatin, respectively. Significant risks for long-term toxicities
      associated with cisplatin and platinum-based regimens were reported. The
      cumulative dose of cisplatin and circulating platinum were reported as risk
      factors. Several single-nucleotide polymorphisms identified patients susceptible
      to cisplatin compared with wild-type individuals. Conclusions: GCT survivors
      cured with cisplatin-based chemotherapy are at risk for long-term side-effects.
      Detection of single-nucleotide polymorphisms could be a valuable tool for
      predicting long-term toxicities. Patient summary: Herein, this article summarizes
      the available evidence of long-term toxicity of cisplatin-based chemotherapy in
      GCT survivors and provide insights from Indiana University.

PMID- 29045505
TI  - Surfaceome profiling enables isolation of cancer-specific exosomal cargo in
      liquid biopsies from pancreatic cancer patients.
AB  - Background: Detection of circulating tumor DNA can be limited due to their
      relative scarcity in circulation, particularly while patients are actively
      undergoing therapy. Exosomes provide a vehicle through which cancer-specific
      material can be enriched from the compendium of circulating non-neoplastic tissue
      derived nucleic acids. We carried out a comprehensive profiling of the pancreatic
      ductal adenocarcinoma (PDAC) exosomal 'surfaceome' in order to identify surface
      proteins that will render liquid biopsies amenable to cancer-derived exosome
      enrichment for downstream molecular profiling. Patients and methods: Surface
      exosomal proteins were profiled in 13 human PDAC and 2 non-neoplastic cell lines
      by liquid chromatography-mass spectrometry. A total of 173 prospectively
      collected blood samples from 103 PDAC patients underwent exosome isolation.
      Droplet digital PCR was used on 74 patients (136 total exosome samples) to
      determine baseline KRAS mutation call rates while patients were on therapy. PDAC
      specific exosome capture was then carried out on additional 29 patients (37
      samples) using an antibody cocktail directed against selected proteins, followed
      by droplet digital PCR analysis. Exosomal DNA in a PDAC patient resistant to
      therapy were profiled using a molecular barcoded, targeted sequencing panel to
      determine the utility of enriched nucleic acid material for comprehensive
      molecular analysis. Results: Proteomic analysis of the exosome 'surfaceome'
      revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151,
      LGALS3BP, HIST2H2BE, and HIST2H2BF. KRAS mutations in total exosomes were
      detected in 44.1% of patients undergoing active therapy compared with 73.0%
      following exosome capture using the selected biomarkers. Enrichment of exosomal
      cargo was amenable to molecular profiling, elucidating a putative mechanism of
      resistance to PARP inhibitor therapy in a patient harboring a BRCA2 mutation.
      Conclusion: Exosomes provide unique opportunities in the context of liquid
      biopsies for enrichment of tumor-specific material in circulation. We present a
      comprehensive surfaceome characterization of PDAC exosomes which allows for
      capture and molecular profiling of tumor-derived DNA.

PMID- 29045506
TI  - Clinical and molecular characterization of patients with cancer of unknown
      primary in the modern era.
AB  - Background: On the basis of historical data, patients with cancer of unknown
      primary (CUP) are generally assumed to have a dismal prognosis with overall
      survival of less than 1 year. Treatment is typically cytotoxic chemotherapy
      guided by histologic features and the pattern of metastatic spread. The purpose
      of this study was to provide a clinical and pathologic description of patients
      with CUP in the modern era, to define the frequency of clinically actionable
      molecular alterations in this population, to determine how molecular testing can
      alter therapeutic decisions, and to investigate novel uses of next-generation
      sequencing in the evaluation and treatment of patients with CUP. Patients and
      methods: Under Institutional Review Board approval, we identified all CUP
      patients evaluated at our institution over a recent 2-year period. We documented
      demographic information, clinical outcomes, pathologic evaluations, next
      generation sequencing of available tumor tissue, use of targeted therapies, and
      clinical trial enrollment. Results: We identified 333 patients with a diagnosis
      of CUP evaluated at our institution from 1 January 2014 through 30 June 2016. Of
      these patients, 150 had targeted next-generation sequencing carried out on
      available tissue. Median overall survival in this cohort was 13 months. Forty
      five of 150 (30%) patients had potentially targetable genomic alterations
      identified by tumor molecular profiling, and 15 of 150 (10%) received targeted
      therapies. Dominant mutation signatures were identified in 21 of 150 (14%),
      largely implicating exogenous mutagen exposures such as ultraviolet radiation and
      tobacco. Conclusions: Patients with CUP represent a heterogeneous population,
      harboring a variety of potentially targetable alterations. Next-generation
      sequencing may provide an opportunity for CUP patients to benefit from novel
      personalized therapies.

PMID- 29045507
TI  - Reply to the letter to the editor 'Including lynch syndrome in personalized
      prognostication and follow-up of stage II and III colon cancer' by Sciallero et
      al.

PMID- 29045508
TI  - Response to 'Survival advantage for etoposide/cisplatin over
      paclitaxel/carboplatin concurrent chemoradiation in patients with inoperable
      stage III NSCLC: a subgroup analysis for ECOG 2 patients would be of great
      interest'.

PMID- 29045509
TI  - The antibody-drug conjugate target landscape across a broad range of tumour
      types.
AB  - Background: Antibody-drug conjugates (ADCs), consisting of an antibody designed
      against a specific target at the cell membrane linked with a cytotoxic agent, are
      an emerging class of therapeutics. Because ADC tumour cell targets do not have to
      be drivers of tumour growth, ADCs are potentially relevant for a wide range of
      tumours currently lacking clear oncogenic drivers. Therefore, we aimed to define
      the landscape of ADC targets in a broad range of tumours. Materials and methods:
      PubMed and ClinicalTrials.gov were searched for ADCs that are or were evaluated
      in clinical trials. Gene expression profiles of 18 055 patient-derived tumour
      samples representing 60 tumour (sub)types and 3520 healthy tissue samples were
      collected from the public domain. Next, we applied Functional Genomic mRNA
      profiling to predict per tumour type the overexpression rate at the protein level
      of ADC targets with healthy tissue samples as a reference. Results: We identified
      87 ADCs directed against 59 unique targets. A predicted overexpression rate of >=
      10% of samples for multiple ADC targets was observed for high-incidence tumour
      types like breast cancer (n = 31 with n = 23 in triple negative breast cancer),
      colorectal cancer (n = 18), lung adenocarcinoma (n = 18), squamous cell lung
      cancer (n = 16) and prostate cancer (n = 5). In rare tumour types we observed,
      amongst others, a predicted overexpression rate of 55% of samples for CD22 and
      55% for ENPP3 in adrenocortical carcinomas, 81% for CD74 and 81% for FGFR3 in
      osteosarcomas, and 95% for c-MET in uveal melanomas. Conclusion: This study
      provides a data-driven prioritization of clinically available ADCs directed
      against 59 unique targets across 60 tumour (sub)types. This comprehensive ADC
      target landscape can guide clinicians and drug developers which ADC is of
      potential interest for further evaluation in which tumour (sub)type.

PMID- 29045510
TI  - The St Gallen International Expert Consensus on the Primary Therapy of Early
      Breast Cancer 2017: the point of view of an International Panel of Experts in
      Radiation Oncology.

PMID- 29045511
TI  - Mechanisms regulating T-cell infiltration and activity in solid tumors.
AB  - T-lymphocytes play a critical role in cancer immunity as evidenced by their
      presence in resected tumor samples derived from long-surviving patients, and
      impressive clinical responses to various immunotherapies that reinvigorate them.
      Indeed, tumors can upregulate a wide array of defense mechanisms, both direct and
      indirect, to suppress the ability of Tcells to reach the tumor bed and mount
      curative responses upon infiltration. In addition, patient and tumor genetics,
      previous antigenic experience, and the microbiome, are all important factors in
      shaping the T-cell repertoire and sensitivity to immunotherapy. Here, we review
      the mechanisms that regulate T-cell homing, infiltration, and activity within the
      solid tumor bed. Finally, we summarize different immunotherapies and
      combinatorial treatment strategies that enable the immune system to overcome
      barriers for enhanced tumor control and improved patient outcome.

PMID- 29045512
TI  - Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients
      after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish
      Group for Research on Sarcoma (GEIS).
AB  - Background: Patients with relapsed unresectable osteosarcoma represents an unmet
      need, so active and safe systemic treatments are required. Fas cell surface death
      receptor and mammalian target of rapamycin pathways are implicated in progressing
      osteosarcoma, and we had preclinical and clinical experience with a scheme that
      targets both pathways. Therefore, we designed a phase II trial with gemcitabine
      plus rapamycin, to determine the efficacy and safety, in this subset of patients.
      Patients and methods: A multicenter, single-arm phase II trial was sponsored by
      the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or
      progressing after standard chemotherapy and unsuitable for metastasectomy
      received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of
      gemcitabine administration, and the day before. The main end point was 4-month
      progression-free survival rate (PFSR), with the assumption that rates higher than
      40% would be considered as an active regimen. Translational research aimed to
      correlate biomarkers with the clinical outcome. Results: Thirty-five patients
      were enrolled and received at least one cycle. PFSR at 4 months was 44%, and
      after central radiologic assessment, 2 partial responses and 14 stabilizations
      (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4
      adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and
      fatigue (15%); however, only three patients had febrile neutropenia. Positive
      protein expression of RRM1 significantly correlated with worse PFS and overall
      survival, while positivity of P-ERK1/2 was correlated with significant better
      overall survival. Conclusion: Gemcitabine plus sirolimus exhibits satisfactory
      antitumor activity and safety in this osteosarcoma population, exceeding the
      prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with
      clinical outcome encourages further prospective investigation.

PMID- 29045513
TI  - DPYD genotype-guided dose individualization to improve patient safety of
      fluoropyrimidine therapy: call for a drug label update.
AB  - The fluoropyrimidine anticancer drugs, especially 5-fluorouracil (5-FU) and
      capecitabine, are frequently prescribed for several types of cancer, including
      breast, colorectal, head and neck and gastric cancer. In the current drug labels
      of 5-FU and capecitabine in the European Union and the United States, no adaptive
      dosing strategies are incorporated for polymorphic metabolism of 5-FU. Although
      treatment with fluoropyrimidines is generally well tolerated, a major clinical
      limitation is that a proportion of the treated population experiences severe,
      sometimes life-threatening, fluoropyrimidine-related toxicity. This toxicity is
      strongly affected by interindividual variability in activity of dihydropyrimidine
      dehydrogenase (DPD), the main metabolic enzyme for inactivation of
      fluoropyrimidines, with an estimated 3%-8% of the population being partially DPD
      deficient. A reduced functional or abrogated DPD enzyme is often caused by
      genetic polymorphisms in DPYD, the gene encoding for DPD, and heterozygous
      carriers of such DPYD polymorphisms have a partial DPD deficiency. When these
      partially DPD deficient patients are treated with a full dose of
      fluoropyrimidines, they are generally exposed to toxic levels of 5-FU and its
      metabolites, and the risk of developing severe treatment-related toxicity is
      therefore significantly increased.Currently, functional and clinical validity is
      well established for four DPYD variants (DPYD*2A, c.2846A>T, c.1679T>G and
      c.1236G>A), as those variants have retrospectively and in a large population
      study prospectively been shown to be associated with increased risk of
      fluoropyrimidine-associated toxicity. Patient safety of fluoropyrimidine
      treatment can be significantly improved by pre-emptive screening for DPYD
      genotype variants and dose reductions in heterozygous DPYD variant allele
      carriers, thereby normalizing 5-FU exposure. Based on the critical appraisal of
      currently available data, adjusting the labels of capecitabine and 5-FU by
      including recommendations on pre-emptive screening for DPYD variants and DPYD
      genotype-guided dose adjustments should be the new standard of care.

PMID- 29045515
TI  - Performance of the cobas HPV Test for the Triage of Atypical Squamous Cells of
      Undetermined Significance Cytology in Cervical Specimens Collected in SurePath.
AB  - Objectives: Determine performance of the cobas human papillomavirus (HPV) test
      for triage of atypical squamous cells of undetermined significance (ASC-US) in
      SurePath. Methods: Women presenting for routine screening had cervical specimens
      collected in SurePath and specimen transport medium (STM); those with ASC-US
      cytology underwent colposcopy. Performance of cobas HPV in SurePath specimens
      that had undergone a preanalytic procedure to reverse possible cross-linking of
      HPV DNA was compared with Hybrid Capture 2 (hc2) specimens in STM. Results: Among
      856 women, HPV prevalence was 45.8%; HPV 16 and HPV 18 prevalences were lower
      than expected in the 21- to 29-year-old group in this highly vaccinated
      population. cobas HPV performance in SurePath was comparable to hc2 in STM.
      Sensitivity and specificity for detection of cervical intraepithelial neoplasia
      grade 3 or worse were 87.5% (95% confidence interval [CI], 71.9%-95.2%) and 55.5%
      (95% CI, 52.1%-58.9%) for cobas and 85.3% (95% CI, 69.9%-93.6%) and 54.7% (95%
      CI, 51.4%-57.9%) for hc2. Sensitivity was negatively affected by random biopsies
      performed at colposcopy; comparable sensitivities were achieved in the
      nonvaccinated and vaccinated populations with disease determined by directed
      biopsy only. Conclusions: Performance of cobas HPV for ASC-US triage in
      pretreated SurePath specimens meets criteria for validation. Preliminary data
      indicate reliable performance of HPV testing in a highly vaccinated population.

PMID- 29045514
TI  - Exploratory analysis of the association of depth of response and survival in
      patients with metastatic non-small-cell lung cancer treated with a targeted
      therapy or immunotherapy.
AB  - Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid
      evaluation of new therapeutic strategies in cancer. However, RECIST does not
      capture the heterogeneity of response in highly active therapies. Depth of tumor
      response may provide a more granular view of response. We explored the
      association between, depth of response (DepOR), with overall survival (OS) and
      progression-free survival (PFS) for patients with NSCLC being treated with an ALK
      inhibitor (ALKi) or an anti-PD-1 antibody (Ab). Methods: Experimental arms from
      two randomized controlled trials (RCTs) of an ALKi and two RCTs of an anti-PD-1
      Ab were separately pooled. Patient responses were grouped into DepOR 'quartiles'
      by percentage of maximal tumor shrinkage (Q1 = 1%-25%, Q2 = 26%-50%, Q3 = 51%
      75%, and Q4 = 76%-100%), Q0 had no shrinkage. We carried out a retrospective
      exploratory responder analysis to evaluate the association between DepOR and OS
      or PFS using hazard ratios (HR) generated by the Cox proportional hazards model.
      Results: In the pooled ALK analysis there were 12, 39, 70, 144, and 40 patients
      in quartiles 0-4, respectively. The DepOR versus PFS/OS analyses HR were:
      0.19/0.94 for Q1 0.11/0.56 for Q2, 0.05/0.28 for Q3, and 0.03/0.05 for Q4. In the
      PD-1 trials within quartiles 0-4 there were 168, 70, 44, 45, and 28 patients,
      respectively. The DepOR versus PFS/OS analyses HR were 0.3/0.52 for Q1, 0.22/0.47
      for Q2, 0.09/0.07 for Q3, and 0.07/0.14 for Q4. Conclusions: Our analysis
      suggests a greater DepOR is associated with longer PFS and OS for patients
      receiving ALKi or anti-PD1 Ab. Overall, this suggests that DepOR may provide an
      additional outcome measure for clinical trials, and may allow better comparisons
      of treatment activity.

PMID- 29045516
TI  - Navigating the highlights of phase III trials: a watchful eye on evidence-based
      radiotherapy.
AB  - Background: Phase III randomized controlled trials (RCTs) are the cornerstone of
      evidence-based oncology. However, there is no exhaustive review describing the
      radiotherapy RTCs characteristics. The objective of the present study was to
      describe features of all phase III RCTs including at least a radiation therapy.
      Methods and materials: Requests were performed in the Medline database (via
      PubMed). The latest update was performed in April 2016, using the following MESH
      terms: 'clinical trials: phase III as topic', 'radiotherapy', 'brachytherapy', as
      keywords. Results: A total of 454 phase III RCTs were identified. Studies were
      mainly based on open (92.1%) multicenter (77.5%) designs, analyzed in intend to
      treat (67.6%), aiming at proving superiority (91.6%) through overall survival
      assessment (46.5%). Most frequently studied malignancies were head and neck
      (21.8%), lung (14.3%) and prostate cancers (9.9%). Patients were mainly recruited
      with a locally advanced disease (73.7%). Median age was 59 years old. Out of 977
      treatment arms, 889 arms experienced radiotherapy, mainly using 3D-conformal
      radiotherapy (288 arms, 32.4%). Intensity-modulated techniques were tested in 12
      arms (1.3%). The intervention was a non-cytotoxic agent addition in 89 studies
      (19.6%), a radiation dose/fractionation modification in 74 studies (16.3%), a
      modification of chemotherapy regimen in 63 studies (13.9%), a chemotherapy
      addition in 63 studies (13.9%) and a radiotherapy addition in 53 trials (11.7%).
      With a median follow-up of 50 months, acute all-grade and grade 3-5 toxicities
      were reported in 49.6% and 69.4% of studies, respectively. Radiotherapy
      technique, follow-up and late toxicities were reported in 60.1%, 74%, and 31.1%
      of studies, respectively. Conclusion: Phase III randomized controlled trials
      featured severe limitations, since a third did not report radiotherapy technique,
      follow-up or late toxicities. The fast-paced technological evolution creates a
      discrepancy between literature and radiotherapy techniques performed in daily
      routine, suggesting that phase III methodology needs to be reinvented.

PMID- 29045517
TI  - Clinicobiological features and prognostic impact of diffuse large B-cell lymphoma
      component in the outcome of patients with previously untreated follicular
      lymphoma.
AB  - Background: The co-existence at diagnosis of follicular lymphoma (FL) and diffuse
      large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a
      transformed lymphoma and accordingly treated although clinicobiological
      information on these patients is scarce. The aim of this study was to analyze the
      initial features and outcome of FL/DLBCL patients in the rituximab era. Patients
      and methods: All patients consecutively diagnosed at a single institution with
      FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n =
      510) as controls. Results: The proportion of the DLBCL component was highly
      variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB
      in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these
      cases. The proportion of DLBCL component did not impact on overall survival (OS).
      Regarding initial characteristics, patients with FL/DLBCL were closer to FL in
      terms of primary nodal origin, good performance status and advanced stage,
      whereas the other features were intermediate between FL and DLBCL. FL/DLBCL
      patients were treated as DLBCL with no further intensification. Complete response
      and primary refractory rates were 65% and 20%, respectively, with these figures
      being similar to DLBCL and worse than FL. Progression-free survival and OS were
      intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL
      and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic
      value for OS in the multivariate analyses. Conclusions: The outcome of FL/DLBCL
      patients is not worse than that of de novo DLBCL. These cases should be treated
      with immunochemotherapy as DLBCL, but intensification with ASCT may not be
      necessary. The biological insights of FL/DLBCL warrants further genetic and
      molecular studies.

PMID- 29045518
TI  - Negative hyper-selection of metastatic colorectal cancer patients for anti-EGFR
      monoclonal antibodies: the PRESSING case-control study.
AB  - Background: Refining the selection of metastatic colorectal cancer patients
      candidates for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies
      beyond RAS and BRAF testing is a challenge of precision oncology. Several
      uncommon genomic mechanisms of primary resistance, leading to activation of
      tyrosine kinase receptors other than EGFR or downstream signalling pathways, have
      been suggested by preclinical and retrospective studies. Patients and methods: We
      conducted this multicentre, prospective, case-control study to demonstrate the
      negative predictive impact of a panel of rare genomic alterations [PRESSING
      (PRimary rESiStance IN RAS and BRAF wild-type metastatic colorectal cancer
      patients treated with anti-eGfr monoclonal antibodies) panel], including HER2/MET
      amplifications, ALK/ROS1/NTRK1-3/RET fusions and PIK3CA mutations. Hypothesizing
      a prevalence of candidate alterations of 15% and 0% in resistant and sensitive
      RAS and BRAF wild-type patients, respectively, with two-sided alpha and beta
      errors of 0.05 and 0.20, 47 patients per group were needed. Results: Forty-seven
      patients per group were included. PRESSING panel alterations were significantly
      more frequent in resistant (24 out of 47, 51.1%) than in sensitive (1 out of 47,
      2.1%) patients (P < 0.001) and in right- (12 out of 29, 41.4%) than left-sided
      (13 out of 65, 20.0%) tumours (P = 0.03). The predictive accuracy of PRESSING
      panel and sidedness was 75.3% and 70.2%, respectively. Among hyper-selected
      patients, right-sidedness was still associated with resistance (P = 0.002). The
      predictive accuracy of the combined evaluation of PRESSING panel and sidedness
      was 80.4%. As a secondary analysis, 8 (17.0%) resistant and 0 sensitive patients
      showed microsatellite instability (P < 0.001). Conclusion: The investigated panel
      of genomic alterations allows refining the selection of RAS and BRAF wild-type
      metastatic colorectal cancer patients candidates for anti-EGFRs, partially
      explaining and further corroborating the predictive ability of primary tumour
      sidedness.

PMID- 29045521
TI  - Analyzing the impact of depth of response on survival in patients with metastatic
      non-small-cell lung cancer.

PMID- 29045519
TI  - Reply to 'The St Gallen International Expert Consensus on the Primary Therapy of
      Early Breast Cancer 2017: the point of view of an International Panel of Experts
      in Radiation Oncology' by Kirova et al.

PMID- 29045522
TI  - Molecular Genetics of Salt-Sensitivity and Hypertension: Role of Renal Epithelial
      Sodium Channel Genes.

PMID- 29045520
TI  - Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients
      with radiographically progressive medullary thyroid carcinoma.
AB  - Background: Primary analysis of the double-blind, phase III Efficacy of XL184
      (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated
      significant improvement in progression-free survival with cabozantinib versus
      placebo in patients with progressive medullary thyroid cancer (MTC). Final
      analysis of overall survival (OS), a key secondary endpoint, was carried out
      after long-term follow-up. Patients and methods: EXAM compared cabozantinib with
      placebo in 330 patients with documented radiographic progression of metastatic
      MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo.
      Final OS and updated safety data are reported. Results: Minimum follow-up was 42
      months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with
      cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did
      not reach statistical significance [stratified hazard ratio (HR), 0.85; 95%
      confidence interval (CI), 0.64-1.12; P = 0.24]. In an exploratory assessment of
      OS, progression-free survival, and objective response rate, cabozantinib appeared
      to have a larger treatment effect in patients with RET M918T mutation-positive
      tumors compared with patients not harboring this mutation. For patients with RET
      M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9
      months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P = 0.03 (not adjusted for
      multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5
      months (HR, 1.12; 95% CI, 0.70-1.82; P = 0.63) in the RET M918T-negative
      subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4
      months with placebo. The safety profile for cabozantinib remained consistent with
      that of the primary analysis. Conclusion: The secondary end point was not met in
      this final OS analysis from the trial of cabozantinib in patients with
      metastatic, radiographically progressive MTC. A statistically nonsignificant
      increase in OS was observed for cabozantinib compared with placebo. Exploratory
      analyses suggest that patients with RET M918T-positive tumors may experience a
      greater treatment benefit with cabozantinib. Trial Registration Number:
      NCT00704730.

PMID- 29045523
TI  - The evolution of chemotherapy for the treatment of prostate cancer.
AB  - Chemotherapy has been explored as a treatment option for metastatic prostate
      cancer since the early 1980s. Docetaxel, a taxane chemotherapeutic, was approved
      for the treatment of men with metastatic castration-resistant prostate cancer in
      2004, and is now standard of care for late stage disease. Recent clinical studies
      demonstrated that patients with metastatic castration-sensitive disease, and
      possibly those with high-risk localized prostate cancer also benefit from
      docetaxel administration, expanding the role of chemotherapy in the prostate
      cancer treatment landscape. Another taxane, cabazitaxel, is approved for post
      docetaxel metastatic castration-resistant prostate cancer. Taxanes and other
      chemotherapeutics, such as carboplatin, are now being tested in combination
      regimens. This review presents an outline of recent and ongoing clinical studies
      assessing docetaxel and its derivative cabazitaxel at different stages of the
      disease, and in various combinations with other agents. We summarize current
      knowledge on biomarkers predictive of response to chemotherapy, which may in
      future be used to guide individualized treatment decisions.

PMID- 29045524
TI  - Combined irradiation and targeted therapy or immune checkpoint blockade in brain
      metastases: toxicities and efficacy.
AB  - Background: Targeted therapies (TT) and immune checkpoint inhibitors (ICI) are
      currently modifying the landscape of metastatic cancer management and are
      increasingly used over the course of many cancers treatment. They allow long-term
      survival with controlled extra-cerebral disease, contributing to the increasing
      incidence of brain metastases (BMs). Radiation therapy remains the cornerstone of
      BMs treatment (either whole brain irradiation or stereotactic radiosurgery), and
      investigating the safety profile of radiation therapy combined with TT or ICI is
      of high interest. Discontinuing an efficient systemic therapy, when BMs
      irradiation is considered, might allow systemic disease progression and, on the
      other hand, the mechanisms of action of these two therapeutic modalities might
      lead to unexpected toxicities and/or greater efficacy, when combined. Patients
      and methods: We carried out a systematic literature review focusing on the safety
      profile and the efficacy of BMs radiation therapy combined with targeted agents
      or ICI, emphasizing on the role (if any) of the sequence of combination scheme
      (drug given before, during, and/or after radiation therapy). Results: Whereas no
      relevant toxicity has been noticed with most of these drugs, the concomitant use
      of some other drugs with brain irradiation requires caution. Conclusion: Most of
      available studies appear to advocate for TT or ICI combination with radiation
      therapy, without altering the clinical safety profiles, allowing the maintenance
      of systemic treatments when stereotactic radiation therapy is considered.
      Cognitive functions, health-related quality of life and radiation necrosis risk
      remain to be assessed. The results of prospective studies are awaited in order to
      complete and validate the above discussed retrospective data.

PMID- 29045525
TI  - Clinical benefit of systemic treatment in patients with advanced pancreatic and
      gastrointestinal neuroendocrine tumours according to ESMO-MCBS and ASCO
      framework.
AB  - Background: Assessment of clinical benefit of systemic treatments of rare
      diseases including gastroenteropancreatic neuroendocrine tumours (GEP-NET) is
      challenging. Recently several tools have been developed to grade the clinical
      benefit of cancer drugs. The European Society for Medical Oncology (ESMO) has
      developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). The American
      Society of Clinical Oncology (ASCO) has developed and revised the ASCO framework
      consisting of the Net Health Benefit (NHB) score juxtaposed against the costs of
      the treatment. In this review, we graded systemic treatments for GEP-NET patients
      with both frameworks. Methods: The electronic databases (PubMed and EMBASE) were
      searched for papers reporting comparative trials, conducted in adult GEP-NET
      patients in the English language. Papers were assessed according to the ESMO-MCBS
      and the NHB part of the ASCO revised Framework (NHB-ASCO-F) by four independent
      assessors, and discrepancies were discussed. Results: The search yielded 32
      trials of which 6 were eligible for grading with the ESMO-MCBS resulting in
      scores of 2 or 3. Eight trials were eligible for grading with the NHB-ASCO-F,
      resulting in scores between 37.6 and 57.4. Trials that were not primary
      assessable by the tools were analysed separately. Consensus between assessors was
      reached in 68% of trials with the ESMO-MCBS and in 23% of trials with the NHB
      ASCO-F. Conclusion: The currently used systemic treatments for GEP-NET patients
      had low scores according to the NHB-ASCO-F and none could be graded as meaningful
      clinical beneficial according to the ESMO-MCBS. Despite the low incidence, the
      heterogeneous patient population and relatively long natural course of NET,
      future studies on new treatment modalities should aim for high clinical benefit
      outcomes.

PMID- 29045526
TI  - LAG-3+ tumor infiltrating lymphocytes in breast cancer: clinical correlates and
      association with PD-1/PD-L1+ tumors.
AB  - Background: Novel immune checkpoint blockade strategies are being evaluated in
      clinical trials and include targeting the lymphocyte activation gene 3 (LAG-3)
      checkpoint, alone or in combination with PD-1/PD-L1 blockade. We investigated LAG
      3 expression and its prognostic value in a large series of breast cancer
      patients, and correlated LAG-3 expression with key biomarkers including PD-1 and
      PD-L1. Experimental design: LAG-3 expression was evaluated by
      immunohistochemistry on two tissue microarray series incorporating 4322 breast
      cancer primary excision specimens (N = 330 in the training and N= 3992 in the
      validation set) linked to detailed clinicopathologic, biomarker and long-term
      clinical outcome data. PD-1 and PD-L1 expressions were also evaluated by
      immunohistochemistry. Stromal or intra-epithelial tumor infiltrating lymphocytes
      (sTILs or iTILs) expressing LAG-3 or PD-1 were assessed by absolute count. PD-L1
      expression was evaluated as the percentage of positive carcinoma cells per core.
      Kaplan-Meier curves and Cox proportional hazard models were used for survival
      analyses. Results: After locking down interpretation cut-offs on the training
      set, LAG-3+ iTILs were found in 11% of cases in the validation set. In both sets,
      LAG-3+ iTILs were significantly associated with negative prognostic factors:
      young age, large tumor size, high proliferation, HER2E and basal-like breast
      cancer subtypes. In multivariate analyses, breast cancer patients with LAG-3+
      iTILs had a significantly improved breast cancer-specific survival [hazard ratio
      (HR): 0.71, 95% CI 0.56-0.90], particularly among estrogen receptor-negative
      patients (HR: 0.50, 95% CI 0.36-0.69). Furthermore, we found that 53% of PD-L1+
      and 61% of PD-1+ cases were also positive for LAG-3+ iTILs. Concurrent
      infiltration of LAG-3+ and CD8+ iTILs was significantly associated with increased
      breast cancer-specific survival (HR: 0.49, 95% CI 0.32-0.74). Conclusion: LAG-3+
      iTILs are enriched in estrogen receptor-negative breast cancers and represent an
      independent favorable prognostic factor. In addition, a high proportion of PD
      1/PD-L1+ tumors are co-infiltrated with LAG-3+ TILs, supporting potential immune
      checkpoint blockade combination strategies as a treatment option for breast
      cancer patients.

PMID- 29045527
TI  - BRAF mutant colorectal cancer: prognosis, treatment, and new perspectives.
AB  - The MAPK cascade plays a crucial role in tumor cell proliferation and survival.
      Accumulating evidence suggests that mutations in the BRAF oncogene are not only
      associated with poor prognosis but also linked with less benefit when treated
      with anti-epidermal growth factor receptor antibodies in metastatic colorectal
      cancer (mCRC). Targeting this molecular aberration has thus become a matter of
      particular interest in mCRC drug development. In contrast to other malignances
      such as BRAF mutant melanoma, efficacy observed with BRAF inhibitors in
      monotherapy in mCRC is poor. Several mechanisms of resistance have been
      identified leading to the development of different treatment strategies that have
      shown promising activity in early clinical trials. Hence, rational combination of
      targeted therapies is expected to further increase the efficacy of selective BRAF
      inhibitors. Herein, we discuss the main clinical and molecular characteristics of
      BRAF mutant colorectal cancer and its translation into the clinic, with a focus
      on developmental therapeutics and combination strategies. In addition, we
      contextualize the available data with potential future approaches that include
      the extended access to next-generation sequencing platforms and gene expression
      strategies for molecular subtyping. These approaches will facilitate the
      identification of certain patient profiles providing more therapeutic
      possibilities.

PMID- 29045528
TI  - Tumor regression and preservation of graft function after combination with anti
      PD-1 immunotherapy without immunosuppressant titration.

PMID- 29045530
TI  - Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA
      analysis in metastatic breast cancer.
AB  - Background: Selection of resistance mutations may play a major role in the
      development of endocrine resistance. ESR1 mutations are rare in primary breast
      cancer but have high prevalence in patients treated with aromatase inhibitors
      (AI) for advanced breast cancer. We investigated the evolution of genetic
      resistance to the first-line AI therapy using sequential ctDNA sampling in
      patients with advanced breast cancer. Patients and methods: Eighty-three patients
      on the first-line AI therapy for metastatic breast cancer were enrolled in a
      prospective study. Plasma samples were collected every 3 months to disease
      progression and ctDNA analysed by digital droplet PCR and enhanced tagged
      amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by
      sequencing were tracked back through samples before progression to study the
      evolution of mutations on therapy. The frequency of novel mutations was validated
      in an independent cohort of available baseline plasma samples in the Study of
      Faslodex versus Exemestane with or without Arimidex (SoFEA) trial, which enrolled
      patients with prior sensitivity to AI. Results: Of the 39 patients who progressed
      on the first-line AI, 56.4% (22/39) had ESR1 mutations detectable at progression,
      which were polyclonal in 40.9% (9/22) patients. In serial tracking, ESR1
      mutations were detectable median 6.7 months (95% confidence interval 3.7-NA)
      before clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression
      plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2% (13/18)
      patients. Mutations in RAS genes were identified in 15.4% (6/39) of progressing
      patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in
      21.2% (24/113) patients although there was no evidence that KRAS mutation status
      was prognostic for progression free or overall survival. Conclusions: Cancers
      progressing on the first-line AI show high levels of genetic heterogeneity, with
      frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high
      frequency. The genetic diversity of AI resistant cancers may limit subsequent
      targeted therapy approaches.

PMID- 29045529
TI  - Impact of genetic variations in the MAPK signaling pathway on outcome in
      metastatic colorectal cancer patients treated with first-line FOLFIRI and
      bevacizumab: data from FIRE-3 and TRIBE trials.
AB  - Background: The MAPK-interacting kinase 1 (MKNK1) is localized downstream of the
      RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation
      MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a
      key player in translational control, whose expression is often upregulated in
      metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1
      increases angiogenesis by upregulating angiogenic factors. We therefore
      hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients
      treated with first-line FOLFIRI and bevacizumab (bev). Patients and methods: A
      total of 567 patients with KRAS wild-type mCRC in the randomized phase III FIRE-3
      and TRIBE trials treated with first-line FOLFIRI/bev (discovery and validation
      cohorts) or FOLFIRI and cetuximab (cet) (control cohort) were included in this
      study. Five single-nucleotide polymorphisms in the MAPK signaling pathway were
      analyzed. Results: AA genotype carriers of the MKNK1 rs8602 single-nucleotide
      polymorphism treated with FOLFIRI/bev in the discovery cohort (FIRE-3) had a
      shorter progression-free survival (PFS) than those harboring any C (7.9 versus
      10.3 months, Hazard ratio (HR) 1.73, P = 0.038). This association could be
      confirmed in the validation cohort (TRIBE) in multivariable analysis (PFS 9.0
      versus 11.0 months, HR 3.04, P = 0.029). Furthermore, AA carriers in the
      validation cohort had a decreased overall response rate (25% versus 66%, P =
      0.049). Conversely, AA genotype carriers in the control group receiving
      FOLFIRI/cet did not show a shorter PFS. By combining both FOLFIRI/bev cohorts the
      worse outcome among AA carriers became more significant (PFS 9.0 versus 10.5
      months) in univariable (HR 1.74, P = 0.015) and multivariable analysis (HR 1.76,
      P = 0.022). Accordingly, AA carriers did also exhibit an inferior overall
      response rate compared with those harboring any C (36% versus 65%, P = 0.005).
      Conclusion: MKNK1 polymorphism rs8602 might serve as a predictive marker in KRAS
      wild-type mCRC patients treated with FOLFIRI/bev in the first-line setting.
      Additionally, MKNK1 might be a promising target for drug development.

PMID- 29045532
TI  - Stevens-Johnson syndrome during nivolumab treatment of NSCLC.

PMID- 29045533
TI  - Liposuction-Augmentation Mammaplasty.
AB  - Background: The female breast loses superior fullness and becomes more ptotic
      over time. Women often present to their plastic surgeon requesting reversal of
      this evolution. While liposuction alone has been proven to lift the breast, no
      solution combining augmentation and liposuction has been reported. Objectives:
      Herein, we introduce a technique called liposuction-augmentation mammaplasty
      (LAM) that can achieve "scarless" lifting or simply volume equalization prior to
      inserting same-sized implants. We then compare its safety and efficacy to two
      gold-standard techniques with similar aims, mastopexy-augmentation mammaplasty
      (MAM) and reduction-augmentation mammaplasty (RAM). Methods: A retrospective 3
      year chart review was conducted on 359 patients (652 breasts) undergoing LAM (n =
      125), MAM (n = 188), and RAM (n = 46). Patient demographics, operative details,
      and revisions were documented. Degree of lift was measured on pre- and
      postoperative photographs using sternal notch-to-nipple distances (SN-N).
      Statistical differences were assessed between the groups. Results: The LAM
      group's mean age and OR time (37 years, 46 minutes) were significantly lower than
      those of MAM (43 years, 90 minutes) and RAM (42 years, 106 minutes). Mean BMIs
      and revision rates were uniform between the LAM and MAM groups (24, 2.5%), but
      significantly higher for RAM (28, 4.6%). Aspirate volumes and resection weights
      averaged 151 cc and 307 g (left breast) and 173 cc and 298 g (right breast).
      Minimum follow up was 12 months. The LAM group's mean SN-N reduction (~6%) was
      statistically significant, albeit much lower than MAM (~16%) and RAM (~22%).
      Conclusions: LAM is a safe, facile, reliable solution for the ptotic, fatty
      breast. Patients can direct their volumetric outcome and enjoy lower costs and
      shorter downtime. Level of Evidence 3: 

PMID- 29045531
TI  - Phylogenetic and functional signals in gymnosperm ovular secretions.
AB  - Background and Aims: Gymnosperms are either wind-pollinated (anemophilous) or
      both wind- and insect-pollinated (ambophilous). Regardless of pollination mode,
      ovular secretions play a key role in pollen capture, germination and growth; they
      are likely also involved in pollinator reward. Little is known about the broad
      scale diversity of ovular secretions across gymnosperms, and how these may relate
      to various reproductive functions. This study analyses the sugar and amino acid
      profiles of ovular secretions across a range of ambophilous (cycads and Gnetales)
      and anemophilous gymnosperms (conifers) to place them in an evolutionary context
      of their possible functions during reproduction. Methods: Ovular secretions from
      13 species representing all five main lineages of extant gymnosperms were
      sampled. High-performance liquid chromatography techniques were used to measure
      sugar and amino acid content. Multivariate statistics were applied to assess
      whether there are significant differences in the chemical profiles of
      anemophilous and ambophilous species. Data were compared with published chemical
      profiles of angiosperm nectar. Chemical profiles were placed in the context of
      phylogenetic relationships. Key results: Total sugar concentrations were
      significantly higher in ovular secretions of ambophilous species than wind
      pollinated taxa such as Pinaceae and Cupressophyta. Ambophilous species had lower
      amounts of total amino acids, and a higher proportion of non-protein amino acids
      compared with anemophilous lineages, and were also comparable to angiosperm
      nectar. Results suggest that early gymnosperms likely had ovular secretion
      profiles that were a mosaic of those associated with modern anemophilous and
      ambophilous species. Ginkgo, thought to be anemophilous, had a profile typical of
      ambophilous taxa, suggesting that insect pollination either exists in Gingko, but
      is undocumented, or that its ancestral populations were insect-pollinated.
      Conclusions: Chemical profiles of ovular secretions of ambophilous gymnosperms
      show a clear signal of pollinator-driven selection, including higher levels of
      carbohydrates than anemophilous taxa, lower levels of amino acids, and the
      presence of specific amino acids, such as beta-alanine, that are known to
      influence insect feeding behaviour and physiology.

PMID- 29045534
TI  - Evaluation of variable selection methods for random forests and omics data sets.
AB  - Machine learning methods and in particular random forests are promising
      approaches for prediction based on high dimensional omics data sets. They provide
      variable importance measures to rank predictors according to their predictive
      power. If building a prediction model is the main goal of a study, often a
      minimal set of variables with good prediction performance is selected. However,
      if the objective is the identification of involved variables to find active
      networks and pathways, approaches that aim to select all relevant variables
      should be preferred. We evaluated several variable selection procedures based on
      simulated data as well as publicly available experimental methylation and gene
      expression data. Our comparison included the Boruta algorithm, the Vita method,
      recurrent relative variable importance, a permutation approach and its parametric
      variant (Altmann) as well as recursive feature elimination (RFE). In our
      simulation studies, Boruta was the most powerful approach, followed closely by
      the Vita method. Both approaches demonstrated similar stability in variable
      selection, while Vita was the most robust approach under a pure null model
      without any predictor variables related to the outcome. In the analysis of the
      different experimental data sets, Vita demonstrated slightly better stability in
      variable selection and was less computationally intensive than Boruta.In
      conclusion, we recommend the Boruta and Vita approaches for the analysis of high
      dimensional data sets. Vita is considerably faster than Boruta and thus more
      suitable for large data sets, but only Boruta can also be applied in low
      dimensional settings.

PMID- 29045535
TI  - SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to
      assess the efficacy of selumetinib plus docetaxel as a second-line treatment of
      patients with advanced or metastatic non-small-cell lung cancer.
AB  - Background: Combination of selumetinib plus docetaxel provided clinical benefit
      in a previous phase II trial for patients with KRAS-mutant advanced non-small
      cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and
      efficacy of selumetinib plus docetaxel for patients with advanced or metastatic
      NSCLC. Patients and methods: Patients who had disease progression after first
      line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d.
      plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus
      docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently
      of KRAS mutation status, but the protocol was amended to include only patients
      with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression
      free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib
      group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type)
      populations. Results: A total of 212 patients were randomized; 69% were KRAS wild
      type. There were no statistically significant improvements in PFS or overall
      survival for overall or KRAS wild-type populations in either selumetinib group
      compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL +
      DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90%
      CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall
      population, a higher objective response rate (ORR; investigator assessed) was
      observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio:
      3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was
      consistent with historical data, without new or unexpected safety concerns
      identified. Conclusion: The primary end point (PFS) was not met. The higher ORR
      with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS
      wild-type patient populations. No clinical benefit was observed with SEL + DOC in
      KRAS wild-type patients compared with docetaxel alone. No unexpected safety
      concerns were reported. Trial identifier: Clinicaltrials.gov NCT01750281.

PMID- 29045537
TI  - Reply to the letter to the editor 'Toxicity adjustment in the ESMO-MCBS: a
      Gestalt approach?' by Del Paggio.

PMID- 29045536
TI  - The Warburg effect: persistence of stem-cell metabolism in cancers as a failure
      of differentiation.
AB  - Background: Two recent observations regarding the Warburg effect are that (i) the
      metabolism of stem cells is constitutive (aerobic) glycolysis while normal
      cellular differentiation involves a transition to oxidative phosphorylation and
      (ii) the degree of glucose uptake of a malignancy as imaged by 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with
      histologic measures of tumor differentiation. Combining these observations, we
      hypothesized that the high levels of glucose uptake observed in poorly
      differentiated cancers may reflect persistence of the glycolytic metabolism of
      stem cells in malignant cells that fail to fully differentiate. Patients and
      methods: Tumor glucose uptake was measured by FDG-PET in 552 patients with
      histologically diverse cancers. We used normal mixture modeling to explore FDG
      PET standardized uptake value (SUV) distributions and tested for associations
      between glucose uptake and histological differentiation, risk of lymph node
      metastasis, and survival. Using RNA-seq data, we carried out pathway and
      transcription factor analyses to compare tumors with high and low levels of
      glucose uptake. Results: We found that well-differentiated tumors had low FDG
      uptake, while moderately and poorly differentiated tumors had higher uptake. The
      distribution of SUV for each histology was bimodal, with a low peak around SUV 2
      5 and a high peak at SUV 8-14. The cancers in the two modes were clinically
      distinct in terms of the risk of nodal metastases and death. Carbohydrate
      metabolism and the pentose-related pathway were elevated in the poorly
      differentiated/high SUV clusters. Embryonic stem cell-related signatures were
      activated in poorly differentiated/high SUV clusters. Conclusions: Our findings
      support the hypothesis that the biological basis for the Warburg effect is a
      persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a
      failure to transition from glycolysis-utilizing undifferentiated cells to
      oxidative phosphorylation-utilizing differentiated cells. We found that cancers
      cluster along the differentiation pathway into two groups, utilizing either
      glycolysis or oxidative phosphorylation. Our results have implications for
      multiple areas of clinical oncology.

PMID- 29045538
TI  - Not only tumor but also therapy heterogeneity.

PMID- 29045539
TI  - The predictive value of interim FDG-PET in early-stage Hodgkin lymphoma is not
      well established.

PMID- 29045540
TI  - Phase II trial of pembrolizumab in patients with platinum refractory germ-cell
      tumors: a Hoosier Cancer Research Network Study GU14-206.
AB  - Background: Despite remarkable results with salvage standard-dose or high-dose
      chemotherapy ~15% of patients with relapsed germ-cell tumors (GCT) are incurable.
      Immune checkpoint inhibitors have produced significant remission in multiple
      tumor types. We report the first study of immunotherapy in patients with GCT.
      Patients and methods: Single arm phase II trial investigating pembrolizumab 200
      mg i.v. Q3weeks until disease progression in patients with relapsed GCT and no
      curable options. Patients age >=18 with GCT who progressed after first-line
      cisplatin-based chemotherapy and after at least one salvage regimen (high-dose or
      standard-dose chemotherapy) were eligible. Centrally assessed programmed death
      ligand 1 (PD-L1) on tumor and infiltrating immune cells was scored. Primary end
      point was overall response rate using immune-related response criteria. Simon two
      stage design with type I error 20% and power 80% was utilized. Results: Twelve
      male patients were enrolled. Median age was 38 years. All patients had
      nonseminoma. Primary site was testis (11) or mediastinum (1). Median AFP 615
      (range 1-32, 760) and hCG 4 (range 0.6-37, 096). Six patients had late relapse
      (>2 years). Median number of previous chemotherapy regimens was 3. Six patients
      received prior high-dose chemotherapy. Two patients had positive PD-L1 staining
      (H-score 90 and 170). Median number of pembrolizumab doses was 2 (range 1-8).
      There were six grade 3 adverse events. No immune-related adverse events were
      reported. No partial or complete responses were observed. Two patients achieved
      radiographic stable disease for 28 and 19 weeks, respectively; both had continued
      rising AFP level despite radiographic stability and had negative PD-L1 staining.
      Conclusion: This is the first reported trial evaluating immune checkpoint
      inhibitors in GCT. Pembrolizumab is well tolerated but does not appear to have
      clinically meaningful single-agent activity in refractory GCT. Clinical trial
      information: NCT02499952.

PMID- 29045541
TI  - From hepatitis C virus infection to B-cell lymphoma.
AB  - In addition to liver disorders, hepatitis C virus (HCV) is also associated with
      extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL),
      especially marginal zone lymphoma, de novo or transformed diffuse large B-cell
      lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and
      clinical observations argue for an association between HCV and
      lymphoproliferative disorders. The causative role of HCV in NHL has been further
      supported by the response to antiviral therapy. Pathophysiological processes at
      stake leading from HCV infection to overt lymphoma still need to be further
      elucidated. Based on reported biological studies, several mechanisms of
      transformation seem however to emerge. A strong body of evidence supports the
      hypothesis of an indirect transformation mechanism by which sustained antigenic
      stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank
      lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could
      play a direct role in cellular transformation, particularly in de novo large B
      cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of
      patients. In this setting, it may be hypothesized that inflammatory cytokines
      stimulate proliferation and transformation of IgH-BCL2 clones that are increased
      during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell
      lymphoproliferation is of prime importance to optimize therapeutic strategies,
      especially with the recent development of new direct-acting antiviral drugs.

PMID- 29045543
TI  - A predictive model of pathologic response based on tumor cellularity and tumor
      infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with
      chemo-free dual HER2 blockade.
AB  - Background: The presence of stromal tumor-infiltrating lymphocytes (TILs) is
      associated with increased pathologic complete response (pCR) and improved
      outcomes in HER2-positive early-breast cancer (BC) treated with anti-HER2-based
      chemotherapy. In the absence of chemotherapy, the association of TILs with pCR
      following anti-HER2 therapy-only is largely unknown. Patients and methods: The
      PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib
      and trastuzumab [and hormonal therapy if hormone receptor (HR)-positive] for 18
      weeks. Percentage of TILs and tumor cellularity were determined at baseline (N =
      148) and at day 15 (D15) of treatment (N = 134). Associations of TILs and tumor
      cellularity with pCR in the breast were evaluated. A combined score based on
      tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and
      validated in D15 samples from 65 patients with HER2-positive disease recruited in
      the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for
      2 weeks, then standard chemotherapy was added for 24 weeks. Results: In PAMELA,
      baseline and D15 TILs were significantly associated with pCR in univariate
      analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were
      significantly associated with pCR. At D15, TILs and tumor cellularity were found
      independently associated with pCR. A combined score (CelTIL) taking into account
      both variables was derived. CelTIL at D15 as a continuous variable was
      significantly associated with pCR, and patients with CelTIL-low and CelTIL-high
      scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15
      was found associated with pCR both as a continuous variable and as group
      categories using a pre-defined cut-off (75.0% versus 33.3%). Conclusions: On
      treatment TILs, but not baseline TILs, are independently associated with response
      following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity
      measured at D15 provides independent predictive information upon completion of
      neoadjuvant anti-HER2-based therapy. Clinical trial number: NCT01973660.

PMID- 29045545
TI  - Liquid biopsy: another tool towards tailored therapy in colorectal cancer.

PMID- 29045542
TI  - Bacterial artificial chromosomes as recombinant reporter constructs to
      investigate gene expression and regulation in echinoderms.
AB  - Genome sequences contain all the necessary information-both coding and regulatory
      sequences-to construct an organism. The developmental process translates this
      genomic information into a three-dimensional form. One interpretation of this
      translation process can be described using gene regulatory network (GRN) models,
      which are maps of interactions among regulatory gene products in time and space.
      As high throughput investigations reveal increasing complexity within these GRNs,
      it becomes apparent that efficient methods are required to test the necessity and
      sufficiency of regulatory interactions. One of the most complete GRNs for early
      development has been described in the purple sea urchin, Strongylocentrotus
      purpuratus. This work has been facilitated by two resources: a well-annotated
      genome sequence and transgenes generated in bacterial artificial chromosome (BAC)
      constructs. BAC libraries played a central role in assembling the S. purpuratus
      genome sequence and continue to serve as platforms for generating reporter
      constructs for use in expression and regulatory analyses. Optically transparent
      echinoderm larvae are highly amenable to transgenic approaches and are therefore
      particularly well suited for experiments that rely on BAC-based reporter
      transgenes. Here, we discuss the experimental utility of BAC constructs in the
      context of understanding developmental processes in echinoderm embryos and
      larvae.

PMID- 29045544
TI  - S-1 as an option for second-line treatment of NSCLC. Is the 'East Side Story'
      applicable in the West?

PMID- 29045546
TI  - Characterization of Adipose Tissue Product Quality Using Measurements of Oxygen
      Consumption Rate.
AB  - Background: Fat grafting is a common procedure in plastic surgery but associated
      with unpredictable graft retention. Adipose tissue (AT) "product" quality is
      affected by the methods used for harvest, processing and transfer, which vary
      widely amongst surgeons. Currently, there is no method available to accurately
      assess the quality of AT. Objectives: In this study, we present a novel method
      for the assessment of AT product quality through direct measurements of oxygen
      consumption rate (OCR). OCR has exhibited potential in predicting outcomes
      following pancreatic islet transplant. Our study aim was to reapportion existing
      technology for its use with AT preparations and to confirm that these
      measurements are feasible. Methods: OCR was successfully measured for en bloc and
      postprocessed AT using a stirred microchamber system. OCR was then normalized to
      DNA content (OCR/DNA), which represents the AT product quality. Results: Mean (+/
      SE) OCR/DNA values for fresh en bloc and post-processed AT were 149.8 (+/- 9.1)
      and 61.1 (+/- 6.1) nmol/min/mg DNA, respectively. These preliminary data suggest
      that: (1) OCR and OCR/DNA measurements of AT harvested using conventional
      protocol are feasible; and (2) standard AT processing results in a decrease in
      overall AT product quality. Conclusions: OCR measurements of AT using existing
      technology can be done and enables accurate, real-time, quantitative assessment
      of the quality of AT product prior to transfer. The availability and further
      validation of this type of assay could enable optimization of fat grafting
      protocol by providing a tool for the more detailed study of procedural variables
      that affect AT product quality.

PMID- 29045547
TI  - Safety of resuming anti-PD-1 in patients with immune-related adverse events
      (irAEs) during combined anti-CTLA-4 and anti-PD1 in metastatic melanoma.
AB  - Background: Combined cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed
      death 1 (PD-1) blockade induces high rates of immune-related adverse events
      (irAEs). The safety of resuming anti-PD-1 in patients who discontinue combination
      therapy due to irAEs is not known. Patients and methods: We assessed patients who
      experienced clinically significant irAEs from combined CTLA-4 and PD-1 blockade
      leading to treatment discontinuation at four academic centers. We assessed the
      safety of resuming anti-PD-1 in terms of recurrent and distinct irAEs. Results:
      Eighty patients discontinued combination therapy due to irAEs, including colitis
      (41%), hepatitis (36%), and pneumonitis (4%). Of these, 96% received
      corticosteroids and 21% received additional immunosuppression (e.g. infliximab).
      All were rechallenged with anti-PD-1, and 14 (18%) had recurrent irAEs at a
      median of 14 days after therapy resumption (six grade 1-2, seven grade 3-4, and
      one grade 5 Steven-Johnson Syndrome). Colitis was less likely to recur than other
      irAEs (6% versus 28%, P = 0.01). Clinically significant but distinct toxicities
      occurred in an additional 17 (21%) patients (11 grade 1-2 and 6 grade 3-4).
      Duration of steroid taper, severity of initial irAEs and use of additional
      immunosuppressants did not predict for toxicity on rechallenge, although patients
      remaining on steroid therapy at anti-PD-1 resumption had higher rates of
      toxicities (55% versus 31%, P = 0.03). Conclusions: Patients who discontinued
      CTLA-4/PD-1 blockade for severe irAEs had relatively high rates of recurrent or
      distinct toxicities with anti-PD-1 resumption. However, many patients,
      particularly with combination-induced colitis, tolerated anti-PD-1 rechallenge
      well, and this approach can be considered in selected patients.

PMID- 29045548
TI  - BOLD Activity During Correct-Answer Feedback in Cued Recall Predicts Subsequent
      Retrieval Performance: An fMRI Investigation Using a Partial Trial Design.
AB  - Receiving correct answer feedback following a retrieval attempt has proven to be
      a highly effective means of learning new information, yet the mechanisms behind
      its efficacy remain poorly understood. Here, fMRI was used to examine how BOLD
      activity measured during a period of feedback could predict subsequent memory
      (SM) performance on a final test. Twenty-five human subjects studied pairs of
      associated words, and were then asked to covertly recall target words in response
      to provided cues. Correct answer feedback was provided immediately after covert
      retrieval attempts. A partial trial design enabled separate modeling of activity
      related to retrieval and to feedback processing. During initial study, typical SM
      effects were observed across the whole brain. During feedback following a failed
      recall attempt, activity in only a subset of these regions predicted final test
      performance. These regions fell within the default mode network (DMN) and
      demonstrated negative SM effects, such that greater deactivation was associated
      with successful recall. No "task-positive" regions demonstrated SM effects in
      this contrast. The obtained results are consistent with a growing literature that
      associates DMN deactivation with successful learning in multiple task contexts,
      likely reflecting differences in the allocation of attentional resources during
      encoding.

PMID- 29045549
TI  - Emerging treatment paradigms for brain metastasis in non-small-cell lung cancer:
      an overview of the current landscape and challenges ahead.
AB  - Advances in the last decade in genomic profiling and the identification of
      druggable targets amenable to biological agents have transformed the management
      and survival of a subgroup of patients with brain metastasis in non-small-cell
      lung cancer. In parallel, clinicians have reevaluated the role of whole brain
      radiotherapy in selected patients with brain metastases to reduce neurocognitive
      toxicity. Continual progress in this understudied field is required: optimization
      of the sequence of schedules for therapies in patients with brain metastases of
      differing genomic profiles, focusing on new strategies to overcome mechanisms of
      biological resistance and increasing drug penetrability into the central nervous
      system. This review summarizes the field to date and possible treatment
      strategies based on current evidence.

PMID- 29045550
TI  - DPYD genotype-guided fluoropyrimidines dose: is it ready for prime time?

PMID- 29045551
TI  - Validation of a Metastatic Assay using biopsies to improve risk stratification in
      patients with prostate cancer treated with radical radiation therapy.
AB  - Background: Radiotherapy is an effective treatment of intermediate/high-risk
      locally advanced prostate cancer, however, >30% of patients relapse within 5
      years. Clinicopathological parameters currently fail to identify patients prone
      to systemic relapse and those whom treatment intensification may be beneficial.
      The purpose of this study was to independently validate the performance of a 70
      gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated
      with radical radiotherapy and androgen deprivation therapy. Patients and methods:
      A bridging cohort of prostate cancer diagnostic biopsy specimens was profiled to
      enable optimization of the Metastatic Assay threshold before further independent
      clinical validation in a cohort of diagnostic biopsies from patients treated with
      radical radiotherapy and androgen deprivation therapy. Multivariable Cox
      proportional hazard regression analysis was used to assess assay performance in
      predicting biochemical failure-free survival (BFFS) and metastasis-free survival
      (MFS). Results: Gene expression analysis was carried out in 248 patients from the
      independent validation cohort and the Metastatic Assay applied. Ten-year MFS was
      72% for Metastatic Assay positive patients and 94% for Metastatic Assay negative
      patients [HR = 3.21 (1.35-7.67); P = 0.003]. On multivariable analysis the
      Metastatic Assay remained predictive for development of distant metastases [HR =
      2.71 (1.11-6.63); P = 0.030]. The assay retained independent prognostic
      performance for MFS when assessed with the Cancer of the Prostate Assessment
      Score (CAPRA) [HR = 3.23 (1.22-8.59); P = 0.019] whilst CAPRA itself was not
      significant [HR = 1.88, (0.52-6.77); P = 0.332]. A high concordance [100% (61.5
      100)] for the assay result was noted between two separate foci taken from 11
      tumours, whilst Gleason score had low concordance. Conclusions: The Metastatic
      Assay demonstrated significant prognostic performance in patients treated with
      radical radiotherapy both alone and independent of standard clinical and
      pathological variables. The Metastatic Assay could have clinical utility when
      deciding upon treatment intensification in high-risk patients. Genomic and
      clinical data are available as a public resource.

PMID- 29045552
TI  - Non-Tuberculous Mycobacteria Infection Following Autologous Fat Grafting on the
      Face.
AB  - Level of Evidence: 5.

PMID- 29045553
TI  - Randomized controlled trial of S-1 versus docetaxel in patients with non-small
      cell lung cancer previously treated with platinum-based chemotherapy (East Asia S
      1 Trial in Lung Cancer).
AB  - Background: Chemotherapy remains a viable option for the management of advanced
      non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted
      therapy and immunotherapy. We evaluated the efficacy of oral 5-fluorouracil-based
      S-1 as second- or third-line therapy compared with standard docetaxel therapy in
      patients with advanced NSCLC. Patients and methods: Patients with advanced NSCLC
      previously treated with >=1 platinum-based therapy were randomized 1 : 1 to
      docetaxel (60 mg/m2 in Japan, 75 mg/m2 at all other study sites; day 1 in a 3
      week cycle) or S-1 (80-120 mg/day, depending on body surface area; days 1-28 in a
      6-week cycle). The primary endpoint was overall survival. The non-inferiority
      margin was a hazard ratio (HR) of 1.2. Results: A total of 1154 patients (577 in
      each arm) were enrolled, with balanced patient characteristics between the two
      arms. Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel
      arms, respectively [HR 0.945; 95% confidence interval (CI) 0.833-1.073; P =
      0.3818]. The upper limit of 95% CI of HR fell below 1.2, confirming non
      inferiority of S-1 to docetaxel. Difference in progression-free survival between
      treatments was not significant (HR 1.033; 95% CI 0.913-1.168; P = 0.6080).
      Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively.
      Significant improvement was observed in the EORTC QLQ-C30 global health status
      over time points in the S-1 arm. The most common adverse drug reactions were
      decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm,
      and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the
      docetaxel arm. Conclusion: S-1 is equally as efficacious as docetaxel and offers
      a treatment option for patients with previously treated advanced NSCLC. Clinical
      trial number: Japan Pharmaceutical Information Center, JapicCTI-101155.

PMID- 29045555
TI  - Reproductive potential and performance of fertility preservation strategies in
      BRCA-mutated breast cancer patients.
AB  - Background: Preclinical evidence suggests a possible negative impact of
      deleterious BRCA mutations on female fertility. However, limited and rather
      conflicting clinical data are available. This study assessed the reproductive
      potential and performance of fertility preservation strategies in BRCA-mutated
      breast cancer patients. Patients and methods: This was a retrospective analysis
      of two prospective studies investigating oocyte cryopreservation and ovarian
      tissue cryopreservation in newly diagnosed early breast cancer patients. In the
      current analysis, baseline anti-Mullerian hormone (AMH) and performance of
      cryopreservation strategies were compared between patients with or without
      germline deleterious BRCA mutations. Results: Out of 156 patients included, 101
      had known BRCA status of whom 29 (18.6%) were BRCA-mutated and 72 (46.1%) had no
      mutation. Median age in the entire cohort was 31 years [interquartile range (IQR)
      28-33). Median AMH levels were 1.8 MUg/l (IQR 1.0-2.7) and 2.6 ug/l (IQR 1.5-4.1)
      in the BRCA-positive and BRCA-negative cohorts, respectively (P = 0.109). Among
      patients who underwent oocyte cryopreservation (N = 29), women in the BRCA
      positive cohort tended to retrieve (6.5 versus 9; P = 0.145) and to cryopreserve
      (3.5 versus 6; P = 0.121) less oocytes than those in the BRCA-negative cohort.
      Poor response rate (i.e. retrieval of <=4 oocytes) was 40.0% and 11.1% in the
      BRCA-positive and BRCA-negative cohorts, respectively (P = 0.147). Among patients
      who underwent ovarian tissue cryopreservation (N = 72), women in the BRCA
      positive cohort tended to have a numerically lower number of oocytes per fragment
      (0.08 versus 0.14; P = 0.193) and per square millimeter (0.33 versus 0.78; P =
      0.153) than those in the BRCA-negative cohort. Two BRCA-mutated patients were
      transplanted after chemotherapy and one delivered at term a healthy baby. No
      difference between BRCA1- and BRCA2-mutated patients was observed in any of the
      above-mentioned outcomes. Conclusion: A consistent trend for reduced reproductive
      potential and performance of cryopreservation strategies was observed in BRCA
      mutated breast cancer patients. Independent validation of these results is
      needed.

PMID- 29045554
TI  - Veliparib with temozolomide or carboplatin/paclitaxel versus placebo with
      carboplatin/paclitaxel in patients with BRCA1/2 locally recurrent/metastatic
      breast cancer: randomized phase II study.
AB  - Background: Homologous recombination defects in BRCA1/2-mutated tumors result in
      sensitivity to poly(ADP-ribose) polymerase inhibitors, which interfere with DNA
      damage repair. Veliparib, a potent poly(ADP-ribose) polymerase inhibitor,
      enhanced the antitumor activity of platinum agents and temozolomide in early
      phase clinical trials. This phase II study examined the safety and efficacy of
      intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in
      patients with BRCA1/2-mutated breast cancer. Patients and methods: Eligible
      patients >=18 years with locally recurrent or metastatic breast cancer and a
      deleterious BRCA1/2 germline mutation were randomized 1 : 1 : 1 to VCP, VT, or
      placebo plus carboplatin/paclitaxel (PCP). Primary end point was progression-free
      survival (PFS); secondary end points included overall survival (OS) and overall
      response rate (ORR). Results: Of 290 randomized patients, 284 were BRCA+,
      confirmed by central laboratory. For VCP versus PCP, median PFS was 14.1 and 12.3
      months, respectively [hazard ratio (HR) 0.789; 95% CI 0.536-1.162; P = 0.227],
      interim median OS 28.3 and 25.9 months (HR 0.750; 95% CI 0.503-1.117; P = 0.156),
      and ORR 77.8% and 61.3% (P = 0.027). For VT (versus PCP), median PFS was 7.4
      months (HR 1.858; 95% CI 1.278-2.702; P = 0.001), interim median OS 19.1 months
      (HR 1.483; 95% CI 1.032-2.131; P = 0.032), and ORR 28.6% (P < 0.001). Safety
      profile was comparable between carboplatin/paclitaxel arms. Adverse events (all
      grades) of neutropenia, anemia, alopecia, and neuropathy were less frequent with
      VT versus PCP. Conclusion: Numerical but not statistically significant increases
      in both PFS and OS were observed in patients with BRCA1/2-mutated
      recurrent/metastatic breast cancer receiving VCP compared with PCP. The addition
      of veliparib to carboplatin/paclitaxel significantly improved ORR. There was no
      clinically meaningful increase in toxicity with VCP versus PCP. VT was inferior
      to PCP. An ongoing phase III trial is evaluating VCP versus PCP, with optional
      continuation single-agent therapy with veliparib/placebo if chemotherapy is
      discontinued without progression, in this patient population. Clinical trial
      information: NCT01506609.

PMID- 29045557
TI  - The Suprapubic Dermoadipose Flap for Aesthetic Reshaping of the Postpregnancy
      Abdomen.
AB  - Background: Postpregnancy full-length diastasis of the recti abdominis muscles is
      a common condition occasionally associated with atrophy of the subcutaneous fat
      located at the midline above and below the umbilicus. Objectives: The authors
      report a preliminary clinical experience with the suprapubic flap to prevent the
      late postoperative contour deformities of the postpregnancy abdomen. Methods:
      Between January 2005 and January 2015, all female patients undergoing
      abdominoplasty with the suprapubic flap were included in the present study.
      Electronic clinical records were reviewed to analyze the patients' ages, body
      mass index (BMI) scores, pregnancies, risk factors, and operative times, followed
      by a telephone-based survey to measure patient satisfaction. Results: Twenty-two
      patients were included. Their ages ranged from 19 to 36 years (mean, 27 years)
      and their BMI ranged from 17.5 to 22.5 kg/m2 (mean, 20.5 kg/m2). Postoperative
      follow up ranged from 12 months to 10 years (mean, 89 months). All patients had
      experienced at least one pregnancy and many of them multiple or twin pregnancies.
      Umbilical hernias were present in 18 patients. There were 5 unusual cases: one
      hematoma, one seroma, and three cases of hypertrophic scarring. Thirteen
      additional minutes were required, on average, to associate the flap. All patients
      were satisfied or very satisfied with the results. Conclusions: The suprapubic
      dermoadipose flap is an effective option to prevent the midline depression that
      would otherwise remain on the hypogastric region of postpregnant slim women with
      midline fat tissue atrophy. Level of Evidence 4: 

PMID- 29045556
TI  - Age, Race, and Gender Factors in Incident Disability.
AB  - Background: Incident disability rates enable the comparison of risk across
      populations. Understanding these by age, sex, and race is important for planning
      for the care of older adults and targeting prevention. Methods: We calculated
      incident disability rates among older adults in the Cardiovascular Health Study,
      a study of 5,888 older adults aged >= 65 years over 6 years of follow-up.
      Disability was defined in the following two ways: (i) self-report of disability
      (severe difficulty or inability) in any of six Activities of Daily Living (ADL),
      and (ii) mobility difficulty (any difficulty walking half a mile or climbing 10
      steps). Incident disability rates were calculated as events per 100 person years
      for age, gender, and race groups. Results: The incidence of ADL disability, and
      mobility difficulty were 2.7 (2.5-2.8), and 9.8 (9.4-10.3) events per 100 person
      years. Women, older participants, and blacks had higher rates in both domains.
      Conclusion: Incidence rates are considerably different based on the domain
      examined as well as age, race, and gender composition of the population.
      Prevention efforts should focus on high risk populations and attempt to
      ameliorate factors that increase risk in these groups.

PMID- 29045558
TI  - Surgery for patients with 'lower grade' glioma: putting assumptions, beliefs and
      convictions into perspective.

PMID- 29045560
TI  - Inflammatory gastrointestinal diseases associated with PD-1 blockade antibodies.
AB  - Background: Immune check-point blockade agents have shown clinical activity in
      cancer patients but are associated with immune-related adverse events that could
      limit their development. The aim of this study was to describe the
      gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer
      treated with anti-PD-1. Methods: this is a retrospective study of consecutive
      adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between
      2013 and 2016. Patients were recruited through a pharmacovigilance registry.
      Patients' data were reviewed by a multidisciplinary committee that included
      gastroenterologists, oncologists and a pathologist. Quantitative variables are
      described by median (range), qualitative variable by frequency (percentage).
      Results: Forty-four patients were addressed to a Gastroenterology unit for a
      suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1,
      which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE
      incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients
      with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13,
      65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and
      haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of
      GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7,
      35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo
      obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in
      acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper
      gastrointestinal tract inflammation. Median time to resolution was 36 days (6
      172) in acute colitis, and 98 days (42-226) in microscopic colitis. Conclusion:
      This study suggests that GI-irAE are different and less frequent with anti PD-1
      than with anti CTLA-4.

PMID- 29045561
TI  - Structural Variability Across the Primate Brain: A Cross-Species Comparison.
AB  - A large amount of variability exists across human brains; revealed initially on a
      small scale by postmortem studies and, more recently, on a larger scale with the
      advent of neuroimaging. Here we compared structural variability between human and
      macaque monkey brains using grey and white matter magnetic resonance imaging
      measures. The monkey brain was overall structurally as variable as the human
      brain, but variability had a distinct distribution pattern, with some key areas
      showing high variability. We also report the first evidence of a relationship
      between anatomical variability and evolutionary expansion in the primate brain.
      This suggests a relationship between variability and stability, where areas of
      low variability may have evolved less recently and have more stability, while
      areas of high variability may have evolved more recently and be less similar
      across individuals. We showed specific differences between the species in key
      areas, including the amount of hemispheric asymmetry in variability, which was
      left-lateralized in the human brain across several phylogenetically recent
      regions. This suggests that cerebral variability may be another useful measure
      for comparison between species and may add another dimension to our understanding
      of evolutionary mechanisms.

PMID- 29045559
TI  - Segregated Excitatory-Inhibitory Recurrent Subnetworks in Layer 5 of the Rat
      Frontal Cortex.
AB  - A prominent feature of neocortical pyramidal cells (PCs) is their numerous
      projections to diverse brain areas. In layer 5 (L5) of the rat frontal cortex,
      there are 2 major subtypes of PCs that differ in their long-range axonal
      projections, corticopontine (CPn) cells and crossed corticostriatal (CCS) cells.
      The outputs of these L5 PCs can be regulated by feedback inhibition from
      neighboring cortical GABAergic cells. Two major subtypes of GABAergic cells are
      parvalbumin (PV)-positive and somatostatin (SOM)-positive cells. PV cells have a
      fast-spiking (FS) firing pattern, while SOM cells have a low threshold spike
      (LTS) and regular spiking. In this study, we found that the 2 PC subtypes in L5
      selectively make recurrent connections with LTS cells. The connection patterns
      correlated with the morphological and physiological diversity of LTS cells. LTS
      cells with high input resistance (Ri) exhibited more compact dendrites and more
      rebound spikes than LTS cells with low Ri, which had vertically elongated
      dendrites. LTS subgroups differently inhibited the PC subtypes, although FS cells
      made nonselective connections with both projection subtypes. These results
      demonstrate a novel recurrent network of inhibitory and projection-specific
      excitatory neurons within the neocortex.

PMID- 29045562
TI  - Attenuation of high-frequency (30-200 Hz) thalamocortical EEG rhythms as
      correlate of anaesthetic action: evidence from dexmedetomidine.
AB  - Background: Gamma (30-80 Hz) and high-gamma (80-200 Hz) thalamocortical EEG
      rhythms are involved in conscious processes and are attenuated by isoflurane and
      propofol. To explore the hypothesis that this attenuation is a correlate of
      anaesthetic action, we characterized the effect dexmedetomidine, a selective
      adrenergic alpha-2 agonist with lesser hypnotic potency, on these rhythms.
      Methods: We recorded local field potentials from barrel cortex and
      ventroposteromedial thalamic nucleus in ten previously instrumented rats to
      measure spectral power (30-50 Hz, 51-75 Hz, 76-125 Hz, 126-200 Hz bands) during
      baseline, at four dexmedetomidine plasma concentrations obtained by i.v. target
      controlled infusion (1.86, 3.75, 5.63 and 7.50 ng ml -1 ), and during recovery.
      Thalamocortical coherence over 0.3-200 Hz was also measured. Results: Loss of
      righting reflex (LORR) occurred with 5.63 ng ml -1 . Dexmedetomidine produced a
      linear concentration-dependent attenuation of cortical ( P <0.04) and thalamic (
      P  <= 0.0051) log power in all bands. Slopes for cortex and thalamus were
      similar. The slope for dexmedetomidine on thalamic power in the 76-200 Hz range
      was less than half that of the other agents ( P <0.003). LORR was associated with
      an increase in delta band (0.3-4.0 Hz) thalamocortical coherence ( P <0.001).
      Increased low-frequency coherence also occurred with propofol and isoflurane.
      Conclusions: Dexmedetomidine attenuates high-frequency thalamocortical rhythms,
      but to a lesser degree than isoflurane and propofol. The main differences between
      dexmedetomidine and the other anaesthetics involved thalamic rhythms, further
      substantiating the link between impaired thalamic function and anaesthesia.
      Increased delta coherence likely reflects cyclic hyperpolarization of
      thalamocortical networks and may be a marker for loss of consciousness.

PMID- 29045563
TI  - Generation of transgenic marmosets using a tetracyclin-inducible transgene
      expression system as a neurodegenerative disease model.
AB  - Controllable transgene expression systems are indispensable tools for the
      production of animal models of disease to investigate protein functions at
      defined periods. However, in nonhuman primates that share genetic, physiological,
      and morphological similarities with humans, genetic modification techniques have
      not been well established; therefore, the establishment of novel transgenic
      models with controllable transgene expression systems will be valuable tools to
      understand pathological mechanism of human disease. In the present study, we
      successfully generated transgenic marmosets using a tetracyclin-inducible
      transgene expression (tet-on) system as a neurodegenerative disease model. The
      mutant human ataxin 3 gene controlled by the tet-on system was introduced into
      marmoset embryos via lentiviral transduction, and 34 transgene-introduced embryos
      were transferred into the uteri of surrogate mothers. Seven live offspring (TET1
      7) were obtained, of which four were transgenic. Fibroblasts from TET1 and 3
      revealed that inducible transgene expression had occurred after treatment with 10
      MUg/mL of doxycycline, while treatment with doxycycline via drinking water
      resulted in 1.7- to 1.8-fold inducible transgene expression compared with before
      treatment. One transgenic second-generation offspring (TET3-3) was obtained from
      TET3, and doxycycline-inducible transgene expression in its fibroblasts showed
      that TET3-3 maintained a high transgene expression level that matched its parent.
      In conclusion, we established a novel transgenic marmoset line carrying the
      mutant human ataxin 3 gene controlled by the tet-on system. The development of
      nonhuman primate models with controllable transgene expression systems will be
      useful for the identification of disease biomarkers and evaluation of the
      efficacy and metabolic profiles of therapeutic candidates.

PMID- 29045564
TI  - Critical Language Areas Show Increased Functional Connectivity in Human Cortex.
AB  - Electrocortical stimulation (ECS) mapping is routinely used to identify critical
      language sites before resective neurosurgery. The precise locations of these
      sites are highly variable across patients, occurring in the frontal, temporal,
      and parietal lobes-it is this variability that necessitates individual patient
      mapping. But why these particular anatomical sites are so privileged in each
      patient is unknown. We hypothesized that critical language sites have greater
      functional connectivity with nearby cortex than sites without critical functions,
      since they serve as central nodes within the language network. Functional
      connectivity across language, motor, and cleared sites was measured in 15
      patients undergoing electrocortiographic (ECoG) mapping for epilepsy surgery.
      Critical language sites had significantly higher connectivity than sites without
      critical functions (P = 0.001), and this also held for motor sites (P = 0.022).
      These data support the hypothesis that critical language sites are highly
      connected within the local cortical network, perhaps explaining why their
      disruption with ECS leads to transient disturbances in language function. It is
      our hope that improved understanding of the mechanisms of ECS will permit
      improved surgical planning and perhaps contribute to the understanding of normal
      language physiology.

PMID- 29045565
TI  - Cigarette sidestream smoke delays nucleotide excision repair: inhibited
      accumulation of repair proteins at DNA lesions.
AB  - Cigarette sidestream smoke (CSS) contains many carcinogens that induce DNA
      damage. DNA damage plays an important role in the initiation of cancer and
      several diseases, and repair is the major defense mechanism; however, the
      relationship between CSS and the repair of DNA damage remains unclear. We herein
      investigated whether CSS influences nucleotide excision repair (NER) in vivo and
      in vitro. HR-1 hairless mouse skin treated with CSS was exposed to UVB, as a
      result of which pyrimidine dimers (cyclobutane pyrimidine dimers (CPDs) and
      pyrimidine(6-4)pyrimidone photoproducts (6-4PPs)) were formed and repaired via
      the NER pathway. The immunohistochemical staining of CPDs revealed that their
      repair was delayed by the CSS treatment. This delay in NER and the underlying
      mechanisms were examined in the human skin cell lines, HaCaT and HSC-1. Dot-blot
      assays, enzyme-linked immunosorbent assay and local ultraviolet irradiation
      assays demonstrated that CSS delayed the repair of CPDs and 6-4PPs. The
      recruitment of the repair molecules, TFIIH, XPA and XPG to pyrimidine dimers was
      markedly inhibited by CSS. Semicarbazide, which reacts with aldehydes, recovered
      the CSS-induced inhibition of NER, and formaldehyde exerted similar inhibitory
      effects to those of CSS. These results suggest that aldehydes in CSS interfere
      with the recruitment of NER molecules to damaged sites, leading to a delay in the
      repair of pyrimidine dimers.

PMID- 29045566
TI  - Aesthetic Surgical Procedures in Men: Major Complications and Associated Risk
      Factors.
AB  - Background: The number of men undergoing cosmetic surgery is increasing in North
      America. Objectives: To determine the incidence and risk factors of major
      complications in males undergoing cosmetic surgery, compare the complication
      profiles between men and women, and identify specific procedures that are
      associated with higher risk of complications in males. Methods: A prospective
      cohort of patients undergoing cosmetic surgery between 2008 and 2013 was
      identified from the CosmetAssure database. Gender specific procedures were
      excluded. Primary outcome was occurrence of a major complication in males
      requiring emergency room visit, hospital admission, or reoperation within 30 days
      of the index operation. Univariate and multivariate analysis evaluated potential
      risk factors for major complications including age, body mass index (BMI),
      smoking, diabetes, type of surgical facility, type of procedure, and combined
      procedures. Results: Of the 129,007 patients, 54,927 underwent gender nonspecific
      procedures, of which 5801 (10.6%) were males. Women showed a higher mean age
      (46.4 +/- 14.1 vs 45.2 +/- 16.7 years, P < 0.01). Men had a higher BMI (27.2 +/-
      4.7 vs 25.7 +/- 4.9 kg/m2, P < 0.01), and were more likely to be smokers (7.1% vs
      5.7%, P < 0.01) when compared to women. Men demonstrated similar overall major
      complication rates compared to women (2.1% vs 2.1%, P = 0.97). When specific
      complications were analyzed further, men had higher hematoma rates, but lower
      incidence of surgical site infection. Additionally, major complications after
      abdominoplasty, facelift surgery, and buttock augmentation were noted to
      preferentially affect males. On multivariate analysis, independent predictors of
      major complications in males included BMI (RR 1.05), hospital or ambulatory
      surgery center procedures (RR 3.47), and combined procedures (RR 2.56).
      Conclusions: Aesthetic surgery in men is safe with low major complication rates.
      Modifiable predictors of complications included BMI and combined procedures.
      Level of Evidence 2: 

PMID- 29045567
TI  - Individualized positive end-expiratory pressure in obese patients during general
      anaesthesia: a randomized controlled clinical trial using electrical impedance
      tomography.
AB  - Background: General anaesthesia leads to atelectasis, reduced end-expiratory lung
      volume (EELV), and diminished arterial oxygenation in obese patients. We
      hypothesized that a combination of a recruitment manoeuvre (RM) and
      individualized positive end-expiratory pressure (PEEP) can avoid these effects.
      Methods: Patients with a BMI >=35 kg m -2 undergoing elective laparoscopic
      surgery were randomly allocated to mechanical ventilation with a tidal volume of
      8 ml kg -1 predicted body weight and (i) an RM followed by individualized PEEP
      titrated using electrical impedance tomography (PEEP IND ) or (ii) no RM and PEEP
      of 5 cm H 2 O (PEEP 5 ). Gas exchange, regional ventilation distribution, and
      EELV (multiple breath nitrogen washout method) were determined before, during,
      and after anaesthesia. The primary end point was the ratio of arterial partial
      pressure of oxygen to inspiratory oxygen fraction ( P aO 2 / F iO 2 ). Results:
      For PEEP IND ( n =25) and PEEP 5 ( n =25) arms together, P aO 2 / F iO 2 and EELV
      decreased by 15 kPa [95% confidence interval (CI) 11-20 kPa, P <0.001] and 1.2
      litres (95% CI 0.9-1.6 litres, P <0.001), respectively, after intubation. Mean (
      sd ) PEEP IND was 18.5 (5.6) cm H 2 O. In the PEEP IND arm, P aO 2 / F iO 2
      before extubation was 23 kPa higher (95% CI 16-29 kPa; P <0.001), EELV was 1.8
      litres larger (95% CI 1.5-2.2 litres; P <0.001), driving pressure was 6.7 cm H 2
      O lower (95% CI 5.4-7.9 cm H 2 O; P <0.001), and regional ventilation was more
      equally distributed than for PEEP 5 . After extubation, however, these
      differences between the arms vanished. Conclusions: In obese patients, an RM and
      higher PEEP IND restored EELV, regional ventilation distribution, and oxygenation
      during anaesthesia, but these differences did not persist after extubation.
      Therefore, lung protection strategies should include the postoperative period.
      Clinical trial registration: German clinical trials register DRKS00004199,
      www.who.int/ictrp/network/drks2/en/ .

PMID- 29045569
TI  - Altered Expression of Reorganized Inputs as They Ascend From the Cuneate Nucleus
      to Cortical Area 3b in Monkeys With Long-Term Spinal Cord Injuries.
AB  - Chronic deafferentations in adult mammals result in reorganization of the brain.
      Lesions of the dorsal columns of the spinal cord at cervical levels in monkeys
      result in expansion of the intact chin inputs into the deafferented hand
      representation in area 3b, second somatosensory (S2) and parietal ventral (PV)
      areas of the somatosensory cortex, ventroposterior lateral nucleus (VPL) of the
      thalamus, and cuneate nucleus of the brainstem. Here, we describe the extent and
      nature of reorganization of the cuneate and gracile nuclei of adult macaque
      monkeys with chronic unilateral lesions of the dorsal columns, and compare it
      with the reorganization of area 3b in the same monkeys. In both, area 3b and the
      cuneate nucleus chin inputs expand to reactivate the deafferented neurons.
      However, unlike area 3b, neurons in the cuneate nucleus also acquire receptive
      fields on the shoulder, neck, and occiput. A comparison with the previously
      published results shows that reorganization in the cuneate nucleus is similar to
      that in VPL. Thus, the emergent topography following deafferentations by spinal
      cord injuries undergoes transformation as the reorganized inputs ascend from
      subcortical nuclei to area 3b. The results help us understand mechanisms of the
      brain plasticity following spinal cord injuries.

PMID- 29045570
TI  - Optogenetic Activation of the Infralimbic Cortex Suppresses the Return of
      Appetitive Pavlovian-Conditioned Responding Following Extinction.
AB  - The infralimbic medial prefrontal cortex (IL) is important for suppressing
      learned behavior after extinction, but whether this function extends to responses
      acquired through appetitive Pavlovian conditioning is unclear. We trained male,
      Long-Evans rats to associate a white-noise conditional stimulus (CS; 10 s; 14
      presentations per session) with 10% liquid sucrose (0.2 mL per CS presentation),
      and recorded entries into the fluid port during the CS. The CS was presented
      without sucrose in subsequent extinction and test sessions. Increasing IL
      activity with pretest microinfusions of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA; 0, 0.3 nmol; 0.3 MUl/side) reduced the
      reinstatement of CS-elicited port entries. The same result was obtained when IL
      neurons that expressed Channelrhodopsin-2 (ChR2) were optically stimulated during
      CS presentations at test (473 nm, 5 ms pulses at 20 Hz for 10.2 s, unilateral).
      Optical stimulation of ChR2-expressing IL neurons during CS presentations also
      reduced spontaneous recovery and context-induced renewal. Furthermore, optical
      stimulation (1) during intertrial intervals had no impact on renewal, (2)
      depolarized ChR2-expressing IL pyramidal neurons in vitro, and (3) preferentially
      increased Fos in ChR2-expressing neurons. These novel converging data highlight a
      critical role for the IL in suppressing the return of appetitive Pavlovian
      conditioned responding following extinction.

PMID- 29045568
TI  - Loss of Protein Kinase Novel 1 (PKN1) is associated with mild systolic and
      diastolic contractile dysfunction, increased phospholamban Thr17 phosphorylation,
      and exacerbated ischaemia-reperfusion injury.
AB  - Aims: PKN1 is a stress-responsive protein kinase acting downstream of small GTP
      binding proteins of the Rho/Rac family. The aim was to determine its role in
      endogenous cardioprotection. Methods and results: Hearts from PKN1 knockout (KO)
      or wild type (WT) littermate control mice were perfused in Langendorff mode and
      subjected to global ischaemia and reperfusion (I/R). Myocardial infarct size was
      doubled in PKN1 KO hearts compared to WT hearts. PKN1 was basally phosphorylated
      on the activation loop Thr778 PDK1 target site which was unchanged during I/R.
      However, phosphorylation of p42/p44-MAPK was decreased in KO hearts at baseline
      and during I/R. In cultured neonatal rat ventricular cardiomyocytes (NRVM) and
      NRVM transduced with kinase dead (KD) PKN1 K644R mutant subjected to simulated
      ischaemia/reperfusion (sI/R), PhosTag(r) gel analysis showed net
      dephosphorylation of PKN1 during sI and early R despite Thr778 phosphorylation.
      siRNA knockdown of PKN1 in NRVM significantly decreased cell survival and
      increased cell injury by sI/R which was reversed by WT- or KD-PKN1 expression.
      Confocal immunofluorescence analysis of PKN1 in NRVM showed increased
      localization to the sarcoplasmic reticulum (SR) during sI. GC-MS/MS and
      immunoblot analysis of PKN1 immunoprecipitates following sI/R confirmed
      interaction with CamKIIdelta. Co-translocation of PKN1 and CamKIIdelta to the
      SR/membrane fraction during sI correlated with phospholamban (PLB) Thr17
      phosphorylation. siRNA knockdown of PKN1 in NRVM resulted in increased basal
      CamKIIdelta activation and increased PLB Thr17 phosphorylation only during sI. In
      vivo PLB Thr17 phosphorylation, Sarco-Endoplasmic Reticulum Ca2+ ATPase (SERCA2)
      expression and Junctophilin-2 (Jph2) expression were also basally increased in
      PKN1 KO hearts. Furthermore, in vivo P-V loop analysis of the beat-to-beat
      relationship between rate of LV pressure development or relaxation and end
      diastolic P (EDP) showed mild but significant systolic and diastolic dysfunction
      with preserved ejection fraction in PKN1 KO hearts. Conclusion: Loss of PKN1 in
      vivo significantly reduces endogenous cardioprotection and increases myocardial
      infarct size following I/R injury. Cardioprotection by PKN1 is associated with
      reduced CamKIIdelta-dependent PLB Thr17 phosphorylation at the SR and therefore
      may stabilize the coupling of SR Ca2+ handling and contractile function,
      independent of its kinase activity.

PMID- 29045572
TI  - Impaired sperm maturation in conditional Lcn6 knockout mice.
AB  - Human LCN6, a lipocalin protein, exhibits predominant expression in epididymis
      and location on the sperm surface. However, the biological function of LCN6 in
      vivo remains unknown. Herein, we found that unlike human LCN6, mouse Lcn6 gene
      encoded two transcript variants that were both upregulated by androgen.
      Subsequently, we generated a conditional knockout mouse model to disrupt Lcn6 in
      the adult and investigate its function. In this model, spermatogenesis was normal
      and Lcn6 deficiency did not affect the natural birth rate of male mice or in
      vitro fertilization ability of their cauda epididymal sperm. Nevertheless, sperm
      from the cauda epididymis of the Lcn6 null mice underwent a sustained increase of
      acrosome reaction frequency whether capacitated or not (P < 0.01). Consistent
      with premature acrosome reaction, sperm from knockout mice had significantly
      increased intracellular calcium content when extracellular calcium was supplied
      (P < 0.01). These results demonstrate an important function of LCN6 in preventing
      calcium overload and premature acrosome reaction of sperm and suggest a potential
      risk factor of LCN6 deficiency for sperm maturation.

PMID- 29045573
TI  - Potential unintended consequences of getting rigorous with scientific rigor.

PMID- 29045571
TI  - Zinc-Induced Metallothionein in Centenarian Offspring From a Large European
      Population: The MARK-AGE Project.
AB  - Metallothionein (MT) family are cysteine-rich proteins that regulate zinc (Zn)
      homeostasis and protect against oxidative damage. Studies in transgenic mice have
      shown that MT favorably influence longevity, although their role in human aging
      is not completely understood. Within the European multicenter study MARK-AGE, we
      analyzed MT induction after Zn treatment in peripheral blood mononuclear cells
      (PBMCs) and its relation with redox biomarkers in 2,936 age-stratified subjects
      (35-75 years) including the general population (RASIG), centenarian offspring
      (GO), and their spouses (SGO). We found that the lymphocyte capability to induce
      MT in response to Zn is not affected by aging. However, GO participants showed
      lower Zn-induced MT and increased basal expression of MT1A, MT1X, and ZnT-1 genes
      than RASIG subjects. Moreover, Zn-induced MT levels were found to be inversely
      related with oxidative stress markers (plasma protein carbonyls, 3-nitrotyrosine,
      and malondialdehyde) in the whole population, but not in GO subjects. In
      conclusion, our results support the hypothesis that the response to Zn is
      attenuated in PBMCs of centenarian offspring compared to the general population
      as a consequence of a tighter control of Zn homeostasis which is likely to
      provide them constant protection against stress stimuli over the whole lifespan.

PMID- 29045574
TI  - Peripheral arterial aneurysms in a toddler.

PMID- 29045575
TI  - Shared and Disorder-Specific Neurocomputational Mechanisms of Decision-Making in
      Autism Spectrum Disorder and Obsessive-Compulsive Disorder.
AB  - Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) often
      share phenotypes of repetitive behaviors, possibly underpinned by abnormal
      decision-making. To compare neural correlates underlying decision-making between
      these disorders, brain activation of boys with ASD (N = 24), OCD (N = 20) and
      typically developing controls (N = 20) during gambling was compared, and
      computational modeling compared performance. Patients were unimpaired on number
      of risky decisions, but modeling showed that both patient groups had lower choice
      consistency and relied less on reinforcement learning compared to controls. ASD
      individuals had disorder-specific choice perseverance abnormalities compared to
      OCD individuals. Neurofunctionally, ASD and OCD boys shared dorsolateral/inferior
      frontal underactivation compared to controls during decision-making. During
      outcome anticipation, patients shared underactivation compared to controls in
      lateral inferior/orbitofrontal cortex and ventral striatum. During reward
      receipt, ASD boys had disorder-specific enhanced activation in inferior
      frontal/insular regions relative to OCD boys and controls. Results showed that
      ASD and OCD individuals shared decision-making strategies that differed from
      controls to achieve comparable performance to controls. Patients showed shared
      abnormalities in lateral-(orbito)fronto-striatal reward circuitry, but ASD boys
      had disorder-specific lateral inferior frontal/insular overactivation, suggesting
      that shared and disorder-specific mechanisms underpin decision-making in these
      disorders. Findings provide evidence for shared neurobiological substrates that
      could serve as possible future biomarkers.

PMID- 29045576
TI  - Activation of cannabinoid receptor 1 is involved in protection against
      mitochondrial dysfunction and cerebral ischaemic tolerance induced by isoflurane
      preconditioning.
AB  - Background: Isoflurane preconditioning (IPC) induces cerebral ischaemic
      tolerance, but the mechanism remains poorly understood. The aim of this study was
      to determine changes in mitochondrial function in the brain after IPC, and
      whether the cannabinoid receptor 1 (CB1R) could be involved in the mechanism of
      mitochondrial protection mediated by IPC. Methods: Adult male Sprague-Dawley rats
      were pretreated with isoflurane 2% for 1 h day -1 , for 5 days consecutively, and
      then subjected to 120 min right middle cerebral artery occlusion. Cannabinoid
      receptor 1 expression in the cellular and mitochondrial membrane was measured.
      The CB1R agonist HU-210 was administered alone, or the antagonists AM251 and
      SR141716A were given to the animals before each preconditioning. Neurological
      scores, infarct volume, apoptosis, and mitochondrial function were examined after
      middle cerebral artery occlusion. Results: Expression of CB1R on cellular and
      mitochondrial membranes was increased 6 h after preconditioning. Both IPC and HU
      210 administration before middle cerebral artery occlusion improved neurological
      outcomes and reduced infarct volume. Isoflurane preconditioning increased the
      expression of the anti-apoptotic proteins Bcl-2 and Bcl-X L and reduced apoptosis
      in neurones. Isoflurane preconditioning and HU-210 also markedly preserved the
      activity of respiratory chain complexes, reduced mitochondrial radical
      generation, preserved mitochondrial membrane potential, and inhibited
      mitochondrial permeability transition pore opening. Cannabinoid receptor 1
      antagonists abolished the improvement in mitochondrial function and the
      neuroprotective effects induced by IPC. Conclusions: Our results indicate that
      IPC elicits brain ischaemic tolerance and mitochondrial protection by activating
      the CB1R, which provides a new mechanism for IPC-induced neuroprotection against
      cerebral ischaemia.

PMID- 29045577
TI  - Drug safety in paediatric anaesthesia.

PMID- 29045578
TI  - Effectiveness of enhanced pulse oximetry sonifications for conveying oxygen
      saturation ranges: a laboratory comparison of five auditory displays.
AB  - Background: Anaesthetists monitor auditory information about a patient's vital
      signs in an environment that can be noisy and while performing other cognitively
      demanding tasks. It can be difficult to identify oxygen saturation (SpO2) values
      using existing pulse oximeter auditory displays (sonifications). Methods: In a
      laboratory setting, we compared the ability of non-clinician participants to
      detect transitions into and out of an SpO2 target range using five different
      sonifications while they performed a secondary distractor arithmetic task in the
      presence of background noise. The control sonification was based on the auditory
      display of current pulse oximeters and comprised a variable pitch with an alarm.
      The four experimental conditions included an Alarm Only condition, a Variable
      pitch only condition, and two conditions using sonifications enhanced with
      additional sound dimensions. Accuracy to detect SpO2 target transitions was the
      primary outcome. Results: We found that participants using the two sonifications
      enhanced with the additional sound dimensions of tremolo and brightness were
      significantly more accurate (83 and 96%, respectively) at detecting transitions
      to and from a target SpO2 range than participants using a pitch only sonification
      plus alarms (57%) as implemented in current pulse oximeters. Conclusions:
      Enhanced sonifications are more informative than conventional sonification. The
      implication is that they might allow anaesthetists to judge better when
      desaturation decreases below, or returns to, a target range.

PMID- 29045579
TI  - Auditory Frequency Representations in Human Somatosensory Cortex.
AB  - Recent studies have challenged the traditional notion of modality-dedicated
      cortical systems by showing that audition and touch evoke responses in the same
      sensory brain regions. While much of this work has focused on somatosensory
      responses in auditory regions, fewer studies have investigated sound responses
      and representations in somatosensory regions. In this functional magnetic
      resonance imaging (fMRI) study, we measured BOLD signal changes in participants
      performing an auditory frequency discrimination task and characterized activation
      patterns related to stimulus frequency using both univariate and multivariate
      analysis approaches. Outside of bilateral temporal lobe regions, we observed
      robust and frequency-specific responses to auditory stimulation in classically
      defined somatosensory areas. Moreover, using representational similarity analysis
      to define the relationships between multi-voxel activation patterns for all sound
      pairs, we found clear similarity patterns for auditory responses in the parietal
      lobe that correlated significantly with perceptual similarity judgments. Our
      results demonstrate that auditory frequency representations can be distributed
      over brain regions traditionally considered to be dedicated to somatosensation.
      The broad distribution of auditory and tactile responses over parietal and
      temporal regions reveals a number of candidate brain areas that could support
      general temporal frequency processing and mediate the extensive and robust
      perceptual interactions between audition and touch.

PMID- 29045580
TI  - Early pitfalls in establishing the British Journal of Anaesthesia.

PMID- 29045581
TI  - 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease
      developed in collaboration with EACTS.

PMID- 29045583
TI  - A crown of thorns-right ventricular outflow tract obstruction caused by calcific
      pericardial ring.

PMID- 29045584
TI  - Oxytocin Fails to Recruit Serotonergic Neurotransmission in the Autistic Brain.
AB  - Oxytocin (OT), a neuropeptide involved in affiliation has been shown to enhance
      social skills in patients with autism spectrum disorders (ASD). Nevertheless, OT
      improvements seem ephemeral. Animal research has demonstrated OT action on
      serotonin (5-HT), an interaction that we also found in the healthy human brain.
      Whether such synaptic interplay also occurs in ASD patients is unknown. To
      address this issue, we mapped the effects of intranasal OT on 5-HT in 18 patients
      with ASD and 24 healthy controls (HC) in a double blind, placebo controlled,
      within subject PET-scan experiment. Each participant underwent two scans:
      baseline and spray (OT or placebo). Using the radiotracer [18 F]MPPF, marking the
      5-HT 1A receptor (5-HT1AR), we measured MPPF-Binding Potential (BP) as an index
      of OT-induced serotonin functional modulation. At baseline ASD patients did not
      differ from controls for 5-HT1AR concentration and distribution. However, while
      OT significantly increased MPPF BP in several brain regions of HC, no changes
      were observed in the ASD group. Serotonin serum concentration analysis
      corroborated these results. Our findings suggest a disturbed OT-serotonin
      interaction in autism. This may limit the potential benefits of OT in these
      patients and open the ways to investigate combined OT-serotonin treatments.

PMID- 29045582
TI  - Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE): A
      Cluster-Randomized Pragmatic Trial of a Multifactorial Fall Injury Prevention
      Strategy: Design and Methods.
AB  - Background: Fall injuries are a major cause of morbidity and mortality among
      older adults. We describe the design of a pragmatic trial to compare the
      effectiveness of an evidence-based, patient-centered multifactorial fall injury
      prevention strategy to an enhanced usual care. Methods: Strategies to Reduce
      Injuries and Develop Confidence in Elders (STRIDE) is a 40-month cluster
      randomized, parallel-group, superiority, pragmatic trial being conducted at 86
      primary care practices in 10 health care systems across United States. The 86
      practices were randomized to intervention or control group using covariate-based
      constrained randomization, stratified by health care system. Participants are
      community-living persons, >=70 years, at increased risk for serious fall
      injuries. The intervention is a comanagement model in which a nurse Falls Care
      Manager performs multifactorial risk assessments, develops individualized care
      plans, which include surveillance, follow-up evaluation, and intervention
      strategies. Control group receives enhanced usual care, with clinicians and
      patients receiving evidence-based information on falls prevention. Primary
      outcome is serious fall injuries, operationalized as those leading to medical
      attention (nonvertebral fractures, joint dislocation, head injury, lacerations,
      and other major sequelae). Secondary outcomes include all fall injuries, all
      falls, and well-being (concern for falling; anxiety and depressive symptoms;
      physical function and disability). Target sample size was 5,322 participants to
      provide 90% power to detect 20% reduction in primary outcome rate relative to
      control. Results: Trial enrolled 5,451 subjects in 20 months. Intervention and
      follow-up are ongoing. Conclusions: The findings of the STRIDE study will have
      important clinical and policy implications for the prevention of fall injuries in
      older adults.

PMID- 29045585
TI  - Multimorbidity in heart failure patients.

PMID- 29045586
TI  - Vestigial aortic inter-leaflet triangle resulting in severe aortic regurgitation.

PMID- 29045587
TI  - Differential Contributions of Default and Dorsal Attention Networks to
      Remembering Thoughts and External Stimuli From Real-Life Events.
AB  - Episodic memories are typically composed of perceptual information derived from
      the external environment and representations of internal states (e.g., one's
      thoughts during prior episodes). To date, however, research has mostly focused on
      the remembrance of external stimuli, such that little is known about how internal
      mentation is represented within episodic memory. In the present fMRI study, we
      examined the neural correlates of these 2 components of episodic memories using a
      novel method of cuing memories from photographs taken during real-life events. We
      found that, compared with corresponding semantic memory tasks, memories for
      internal thoughts and external elements were associated with activity in brain
      areas supporting episodic recollection. Most importantly, however, the 2 kinds of
      memories also showed differential activation in large-scale brain networks: the
      remembrance of external elements was associated with greater activity in the
      dorsal attention network, whereas memories of internal thoughts mainly recruited
      default network areas. These findings shed new light on the representation of
      internal and external aspects of prior experience within episodic memory. The
      default network may contribute to the reinstatement of thoughts experienced
      during past events, whereas the dorsal attention network may support the
      allocation of attention to visuospatial features within episodic memory
      representations.

PMID- 29045588
TI  - The mycotoxin metabolite deepoxy- deoxynivalenol increases apoptosis and
      decreases steroidogenesis in bovine ovarian theca cells.
AB  - The mycotoxin deoxynivalenol (DON) has been shown to inhibit ovarian granulosa
      cell function in cattle in vitro, but it is not known whether DON or its
      metabolite deepoxy-DON (DOM-1) affects theca cell function. The objectives of
      this study were to determine the effects of DON and of DOM-1 on theca cell
      steroidogenesis and apoptosis, and to determine the main pathways through which
      they act. Bovine theca cells were cultured in a nonluteinizing serum-free culture
      system, and challenged with DON or DOM-1 for 4 days to measure steroidogenesis
      and apoptosis, for 1-8 h to measure immediate-early genes, and for 5-60 min to
      measure phosphorylation of intracellular signaling proteins. Addition of DON
      decreased progesterone secretion at doses as low as 0.5 ng/ml but had no effect
      on testosterone secretion. Addition of DOM-1 inhibited progesterone and
      testosterone secretion at 0.5 ng/ml. Treatment of cells with 1 ng/ml DOM-1
      increased the proportion of apoptotic cells, whereas DON had no effect. Addition
      of DON or DOM-1 stimulated phosphorylation of EIF2AK2, MAPK3/1, and AKT. However,
      DON inhibited and DOM-1 stimulated MAPK14 phosphorylation. DON increased the
      levels of mRNA encoding early-immediate genes EGR1, EGR3, and FOS, whereas DOM-1
      was without effect. DOM-1 but not DON increased abundance of mRNA of the
      endoplasmic reticulum (ER) stress-related proteins, PRKRA and ATF4. We conclude
      that DOM-1 has a major impact on theca function in cattle, and possibly induces
      theca cell apoptosis through ER stress.

PMID- 29045590
TI  - An interview with Katrin Hinrichs.

PMID- 29045589
TI  - Standardization of adult transthoracic echocardiography reporting in agreement
      with recent chamber quantification, diastolic function, and heart valve disease
      recommendations: an expert consensus document of the European Association of
      Cardiovascular Imaging.
AB  - Aims: This European Association Cardiovascular Imaging (EACVI) Expert Consensus
      document aims at defining the main quantitative information on cardiac structure
      and function that needs to be included in standard echocardiographic report
      following recent ASE/EACVI chamber quantification, diastolic function, and heart
      valve disease recommendations. The document focuses on general reporting and
      specific pathological conditions such as heart failure, coronary artery and
      valvular heart disease, cardiomyopathies, and systemic diseases. Methods and
      results: Demographic data (age, body surface area, blood pressure, and heart
      rhythm and rate), type (vendor and model) of ultrasound system used and image
      quality need to be reported. In addition, measurements should be normalized for
      body size. Reference normal values, derived by ASE/EACVI recommendations, shall
      always be reported to differentiate normal from pathological conditions. This
      Expert Consensus document suggests avoiding the surveillance of specific variable
      using different ultrasound techniques (e.g. in echo labs with high expertise in
      left ventricular ejection fraction by 3D and not by 2D echocardiography). The
      report should be also tailored in relation with different cardiac pathologies,
      quality of images, and needs of the caregivers. Conclusion: The conclusion should
      be concise reflecting the status of left ventricular structure and function, the
      presence of left atrial and/or aortic dilation, right ventricular dysfunction,
      and pulmonary hypertension, leading to an objective communication with the
      patient health caregiver. Variation over time should be considered carefully,
      taking always into account the consistency of the parameters used for comparison.

PMID- 29045591
TI  - SAGE2: parallel human genome assembly.
AB  - Summary: De novo genome assembly of next-generation sequencing data is a
      fundamental problem in bioinformatics. There are many programs that assemble
      small genomes, but very few can assemble whole human genomes. We present a new
      algorithm for parallel overlap graph construction, which is capable of assembling
      human genomes and improves upon the current state-of-the-art in genome assembly.
      Availability and implementation: SAGE2 is written in C ++ and OpenMP and is
      freely available (under the GPL 3.0 license) at github.com/lucian-ilie/SAGE2.
      Contact: ilie@uwo.ca. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29045592
TI  - Impact of Public Safety Policies on Human Immunodeficiency Virus Transmission
      Dynamics in Tijuana, Mexico.
AB  - Background: North Tijuana, Mexico is home to many individuals at high risk for
      transmitting and acquiring human immunodeficiency virus (HIV). Recently, policy
      shifts by local government impacted how these individuals were handled by
      authorities. Here we examined how this affected regional HIV transmission
      dynamics. Methods: HIV pol sequences and associated demographic information were
      collected from 8 research studies enrolling persons in Tijuana and were used to
      infer viral transmission patterns. To evaluate the impact of recent policy
      changes on HIV transmission dynamics, qualitative interviews were performed on a
      subset of recently infected individuals. Results: Between 2004 and 2016, 288
      unique HIV pol sequences were obtained from individuals in Tijuana, including
      46.4% from men who have sex with men, 42.1% from individuals reporting
      transactional sex, and 27.8% from persons who inject drugs (some individuals had
      >1 risk factor). Forty-two percent of sequences linked to at least 1 other
      sequence, forming 37 transmission clusters. Thirty-two individuals seroconverted
      during the observation period, including 8 between April and July 2016. Three of
      these individuals were putatively linked together. Qualitative interviews
      suggested changes in policing led individuals to shift locations of residence and
      injection drug use, leading to increased risk taking (eg, sharing needles).
      Conclusions: Near real-time molecular epidemiologic analyses identified a cluster
      of linked transmissions temporally associated with policy shifts. Interviews
      suggested these shifts may have led to increased risk taking among individuals at
      high risk for HIV acquisition. With all public policy shifts, downstream impacts
      need to be carefully considered, as even well-intentioned policies can have major
      public health consequences.

PMID- 29045593
TI  - A teleost androgen promotes development of primary ovarian follicles in coho
      salmon and rapidly alters the ovarian transcriptome.
AB  - Recent studies using several teleost models have revealed that androgens increase
      the size of previtellogenic (primary and/or early secondary) ovarian follicles.
      To explore our hypothesis that androgens drive the development of primary
      follicles into early secondary follicles, and to determine the mechanisms
      underlying these androgenic effects, we exposed juvenile coho salmon to near
      physiological and relatively sustained levels of the nonaromatizable androgen 11
      ketotestosterone (11-KT). This resulted in significant growth of primary ovarian
      follicles after 10 and 20 days, with follicles after 20 days displaying a
      morphological phenotype characteristic of early secondary follicles (presence of
      cortical alveoli). Utilizing the same experimental approach, we then analyzed how
      11-KT rapidly altered the ovarian transcriptome after 1 and 3 days of treatment.
      RNA-Seq analysis revealed that 69 (day 1) and 1,022 (day 3) contiguous sequences
      (contigs) were differentially expressed relative to controls. The differentially
      expressed contigs mapped to genes including those encoding proteins involved in
      gonadotropin, steroid hormone, and growth factor signaling, and in cell and
      ovarian development, including genes with putative androgen-response elements.
      Biological functions and canonical pathways identified as potentially altered by
      11-KT include those involved in ovarian development, tissue differentiation and
      remodeling, and lipid metabolism. We conclude that androgens play a major role in
      stimulating primary ovarian follicle development and the transition into
      secondary growth.

PMID- 29045594
TI  - Increases in Asymptomatic Early Syphilis May Reflect Increases in Repeated
      Episodes of Syphilis and Not Enhanced Screening.

PMID- 29045595
TI  - Performance of Apanteles hemara (Hymenoptera: Braconidae) on two Amaranth Leaf
      webbers: Spoladea recurvalis and Udea ferrugalis (Lepidoptera: Crambidae).
AB  - Amaranth is an African indigenous vegetable that is gaining popularity due to its
      nutritional, medicinal, and economic values. In East Africa, frequent outbreaks
      of Lepidopteran leaf-webbers, Spoladea recurvalis F. (Lepidoptera: Crambidae) and
      Udea ferrugalis Hubner (1976) are reported on this crop, causing up to 100%
      foliage loss. The larval endoparasitoid Apanteles hemara Nixon is also frequently
      found associated with these pests during the outbreaks, however, its performance
      on both pests has never been documented. Laboratory studies were therefore
      carried out to assess the acceptability and suitability of S. recurvalis and U.
      ferrugalis to A. hemara. Both leaf-webber species were accepted by and suitable
      for the parasitoid. The mean host searching time and oviposition attempts were
      neither affected by rearing host nor test host. The total developmental time of
      A. hemara ranged between 10.6 +/- 0.16 and 12.8 +/- 0.30 days on both hosts. The
      sex ratio of the parasitoid was female biased when reared on S. recurvalis but
      male biased on U. ferrugalis. When offered 50 larvae of leaf-webbers for 24 h, a
      single female A. hemara achieved parasitism rates from 42.63 +/- 5.80 to 44.55 +/
      5.95, while a cohort of five females resulted in parasitism rates between 87.25
      +/- 2.70 and 94.67 +/- 1.98 %. There was no significant difference between hosts
      in regard to progeny fitness at each parasitoid density. The parasitoid also
      caused significant nonreproductive larval mortalities in the hosts. The
      implications of these findings for mass rearing of the parasitoid as well as for
      conservation and augmentative biological control of amaranth lepidopteran leaf
      webbers in East Africa are discussed.

PMID- 29045596
TI  - The relationship between cardiovascular magnetic resonance imaging measurement of
      extracellular volume fraction and clinical outcomes in adults with repaired
      tetralogy of Fallot.
AB  - Aims: Our aims were to explore cardiac magnetic resonance quantification of
      myocardial extracellular volume (ECV) in adults with repaired tetralogy of Fallot
      (rTOF) when compared with healthy controls and to investigate the association
      between ECV and major adverse cardiovascular outcomes. Methods and results: We
      prospectively recruited adults with rTOF (n = 44, 59% male, 32.9 +/- 13.6 years)
      and evaluated right ventricular (RV) and left ventricular (LV) ECV by pre/post
      gadolinium T1 measurements (modified Look-Locker inversion recovery technique) on
      a 1.5-T Siemens scanner compared with the healthy controls (n = 10, 50% male,
      31.5 +/- 4.4 years). The primary end point was a composite of death, out-of
      hospital cardiac arrest, heart failure (HF) requiring admission for escalation of
      therapy, or haemodynamically significant ventricular tachycardia (VT) (lasting
      >30 s and/or resulting in invasive therapy). The association between ECV and
      adverse events was assessed using Cox proportional hazard models [median follow
      up 236 days, interquartile range (IQR) 38-342]. RVECV was higher in patients
      compared with the controls (31.5 +/- 5.4% vs. 26.3 +/- 2.1%, P = 0.027). The
      following major adverse events occurred (n = 9, 21%): death (n = 1), out-of
      hospital cardiac arrest (n = 1), HF (n = 1), and VT (n = 6). RVECV was higher
      among those with an adverse event compared to those without (35.0 +/- 5.5% vs.
      29.6 +/- 4.5%, P = 0.014) and was associated with increased risk for adverse
      events [hazard ratio 1.13, 95% confidence interval (1.01-1.28); P = 0.037]. LVECV
      was not associated with adverse events (P = 0.667). Conclusion: Increased RVECV
      is associated with adverse cardiovascular events in adults with rTOF. These
      results may lead to further studies exploring the potential role for RVECV in
      risk stratification and targeted therapeutic interventions in this population.

PMID- 29045597
TI  - Delayed-onset lung injury after balloon pulmonary angioplasty for chronic
      thromboembolic pulmonary hypertension-a case report.

PMID- 29045598
TI  - Prognostic value of pulmonary blood volume by first-pass contrast-enhanced CMR in
      heart failure outpatients: the PROVE-HF study.
AB  - Aims: Pulmonary blood volume (PBV) is a novel clinical application of
      cardiovascular magnetic resonance (CMR) imaging for the quantitative grading of
      haemodynamic congestion. In this study, we aimed to assess the prognostic value
      of PBV in a cohort of outpatients with chronic heart failure (HF). Methods and
      results: One hundred and twelve consecutive patients (91 men, 67 +/- 12 years)
      and 53 age- and sex-matched healthy controls underwent echocardiography and
      contrast-enhanced CMR. PBV was calculated as the product of stroke volume and the
      number of cardiac cycles for an intravenous bolus of gadolinium contrast to pass
      through the pulmonary circulation determined by first-pass perfusion imaging.
      Compared with healthy controls, HF outpatients showed significantly higher PBV
      index (PBVI, 308 +/- 92 vs. 373 +/- 175, mL/m2, P = 0.012) and pulmonary transit
      time (6.8 +/- 1.8 vs. 9.5 +/- 4 s, P <=0.001). During a median follow-up of 26 +/
      17 months, 27 patients (24%) reached the composite end point of cardiovascular
      death, HF hospitalization, or sustained ventricular arrhythmias/appropriate
      implantable cardioverter-defibrillator intervention. Using a cut-off point of
      PBVI >492 mL/m2, corresponding to two standard deviations above the mean of
      healthy controls, event-free survival was significantly lower in patients with
      higher PBVI (P < 0.001). At multivariable-adjusted Cox regression analysis, PBVI
      was an independent predictor of the composite cardiovascular end point (per 10%
      increase hazard ratio 1.31, 95% confidence interval: 1.02-1.69, P = 0.03).
      Conclusions: PBVI is a novel application of perfusion CMR potentially useful to
      quantitatively determine haemodynamic congestion as a surrogate marker of left
      ventricular diastolic dysfunction. PBVI might prove to be helpful in stratifying
      the prognosis of asymptomatic or mildly symptomatic patients with left
      ventricular dysfunction.

PMID- 29045599
TI  - A Modulatory Effect of Brief Passive Exposure to Non-linguistic Sounds on
      Intrinsic Functional Connectivity: Relevance to Cognitive Performance.
AB  - A growing literature on resting-state fMRI (R-fMRI) has explored the impact of
      preceding sensory experience on intrinsic functional connectivity (iFC). However,
      it remains largely unknown how passive exposure to irrelevant auditory stimuli,
      which is a constant in everyday life, reconfigures iFC. Here, we directly
      compared pre- and post-exposure R-fMRI scans to examine: 1) modulatory effects of
      brief passive exposure to repeating non-linguistic sounds on subsequent iFC, and
      2) associations between iFC modulations and cognitive abilities. We used an
      exploratory regional homogeneity (ReHo) approach that indexes local iFC, and
      performed a linear mixed-effects modeling analysis. A modulatory effect
      (increase) in ReHo was observed in the right superior parietal lobule (R.SPL)
      within the parietal attention network. Post hoc seed-based correlation analyses
      provided further evidence for increased parietal iFC (e.g., R.SPL with the right
      inferior parietal lobule). Notably, less iFC modulation was associated with
      better cognitive performance (e.g., word reading). These results suggest that: 1)
      the parietal attention network dynamically reconfigures its iFC in response to
      passive (thus irrelevant) non-linguistic sounds, but also 2) minimization of iFC
      modulation in the same network characterizes better cognitive performance. Our
      findings may open up new avenues for investigating cognitive disorders that
      involve impaired sensory processing.

PMID- 29045600
TI  - Development and Validation of a Stability-indicating Reversed-phase UPLC-UV
      Method for the Assay of Imidacloprid and Estimation of its Related Compounds.
AB  - Imidacloprid is used as an active pharmaceutical ingredient (API) in veterinary
      drugs to control fleas and ticks for dogs and cats. Here we are reporting for the
      first time a validated stability-indicating reversed-phase UPLC-UV method for the
      assay of imidacloprid and estimation of its related compounds. The stability
      indicating capability of this method has been demonstrated by a forced
      degradation study. All related compounds including processing impurities,
      imidacloprid API and degradates from stressed samples were well separated from
      each other. Structures of major degradates from forced degradation study were
      elucidated through UPLC-MS/MS and key degradation pathways were proposed from the
      proposed chemical structures of major degradates. The UPLC-UV method is carried
      out using an HSS T3 column (C18, 2.1 * 30 mm, 1.8 MUm particle size) maintained
      at 30 degrees C with mobile phase A (0.05% v/v of phosphoric acid in water) and
      mobile phase B (methanol/acetonitrile 75/25 v/v). Analytes are separated by a
      gradient elution and detected at 270 nm. The UPLC method is green and fast with
      only 6.5 min run time and about 3.5 ml mobile phase consumption for each sample
      analysis. The UPLC-UV method was validated according to ICH guidelines.

PMID- 29045602
TI  - Does routinely collected patient-reported outcome data represent the actual case
      mix of elective coronary revascularization patients?
AB  - Aims: Patient-reported outcomes (PROs) are valuable for effectiveness evaluation,
      but it is unknown whether the patient views obtained represent the actual case
      mix. We studied the representativeness of the responses obtained to a routinely
      administered health-related quality of life (HRQoL) questionnaire in a cardiology
      unit. Methods and results: Elective coronary artery bypass grafting (CABG; n =
      404) and percutaneous coronary intervention (PCI; n = 738) patients operated
      during June 2012 to August 2014 in the Heart Center, Kuopio University Hospital.
      The characteristics of the patients with a baseline (n = 260 and 290 for CABG and
      PCI, respectively) or both baseline and follow-up HRQoL measurements (n = 203 and
      189 for CABG and PCI, respectively) were compared with those who did not respond
      (n = 144 and 448 for CABG and PCI). Baseline questionnaires were less likely
      obtained from older CABG patients (odds ratio 0.51, 95% confidence interval 0.28
      0.91) and those with more severe disease (0.20, 0.05-0.79). Among PCI patients,
      women (0.64, 0.45-0.91), smokers (0.74, 0.53-1.04), and those with more severe
      disease (0.26, 0.13-0.52) or more hospital days were underrepresented.
      Conclusion: Routinely collected PROs in cardiac patients may be biased towards
      younger and healthier patients. This needs to be recognized when evaluating the
      representativeness of such data. The routine collection of these data should be
      adequately resourced.

PMID- 29045601
TI  - Genomic Changes Associated with Reproductive and Migratory Ecotypes in Sockeye
      Salmon (Oncorhynchus nerka).
AB  - Mechanisms underlying adaptive evolution can best be explored using paired
      populations displaying similar phenotypic divergence, illuminating the genomic
      changes associated with specific life history traits. Here, we used paired
      migratory [anadromous vs. resident (kokanee)] and reproductive [shore- vs. stream
      spawning] ecotypes of sockeye salmon (Oncorhynchus nerka) sampled from seven
      lakes and two rivers spanning three catchments (Columbia, Fraser, and Skeena) in
      British Columbia, Canada to investigate the patterns and processes underlying
      their divergence. Restriction-site associated DNA sequencing was used to genotype
      this sampling at 7,347 single nucleotide polymorphisms, 334 of which were
      identified as outlier loci and candidates for divergent selection within at least
      one ecotype comparison. Sixty-eight of these outliers were present in two or more
      comparisons, with 33 detected across multiple catchments. Of particular note, one
      locus was detected as the most significant outlier between shore and stream
      spawning ecotypes in multiple comparisons and across catchments (Columbia,
      Fraser, and Snake). We also detected several genomic islands of divergence, some
      shared among comparisons, potentially showing linked signals of differential
      selection. The single nucleotide polymorphisms and genomic regions identified in
      our study offer a range of mechanistic hypotheses associated with the genetic
      basis of O. nerka life history variation and provide novel tools for informing
      fisheries management.

PMID- 29045603
TI  - Ustekinumab Drug Levels in Maternal and Cord Blood in a Woman With Crohn's
      Disease Treated Until 33 Weeks of Gestation.
AB  - A 35-year old woman with ileocolonic, perianal, and vulval Crohn's disease was
      treated with subcutaneous ustekinuamb [USK] throughout pregnancy. Dose intervals
      were shortened from 6-weekly to 4-weekly to maintain clinical remission. The last
      dose of USK was administered at 33 weeks of gestation, and a healthy baby boy was
      delivered by caesarean section at 37 weeks. Maternal trough USK levels remained
      stable during pregnancy. Cord blood USK levels were nearly 2-fold higher than
      contemporaneous maternal serum levels. To our knowledge, this is the first report
      of maternal and cord USK levels in a patient with Crohn's disease.

PMID- 29045604
TI  - Increases in Neisseria gonorrhoeae With Reduced Susceptibility to Azithromycin
      Among Men Who Have Sex With Men in Seattle, King County, Washington, 2012-2016.
AB  - Background: Antimicrobial-resistant Neisseria gonorrhoeae is a major public
      health threat. The Centers for Disease Control and Prevention (CDC) recommends
      ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment.
      Resistance to AZM could affect gonorrhea control efforts. Methods: Using
      gonococcal isolates collected at the Public Health-Seattle & King County (PHSKC)
      Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014
      2016, we compared cases with the CDC AZM alert value minimum inhibitory
      concentration (MIC) (>=2 ug/mL) to those with AZM MIC <=1 ug/mL, antimicrobial
      susceptibility profiles and clinical outcomes. Results: In 2012 and 2013, none of
      the 263 patients from whom we isolated N. gonorrhoeae from the urethra were
      infected with organisms with an AZM MIC >=2 ug/mL. Between 2014 and 2016, 4.4% of
      926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these
      cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014
      2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value
      isolates had concomitant cephalosporin resistance. There were 2 potential
      treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1
      pharyngeal infection that persisted after study drug. Conclusions: Among MSM with
      gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The
      World Health Organization recommends changing treatment guidelines when >5% of
      isolates are resistant to a recommended drug. The emergence of resistant AZM
      gonorrhea should prompt reconsideration of current treatment recommendations, and
      highlights the need for new therapies for gonorrhea.

PMID- 29045606
TI  - Clinical and Laboratory Features of Group B Streptococcus Meningitis in Infants
      and Newborns: Study of 848 Cases in France, 2001-2014.
AB  - Background: Group B Streptococcus (GBS) disease is the leading cause of neonatal
      bacterial meningitis despite women receiving an intravenous antibiotic
      prophylaxis during labor. We aimed to describe GBS meningitis in children <1 year
      old in France. Methods: Clinical and biological data of GBS meningitis gathered
      by the Association Clinique et Therapeutique Infantile du Val de Marne (ACTIV)
      were analyzed. The cases were classified by age: 0-6 days old (early-onset
      disease [EOD]), newborns and infants 7-89 days old (late-onset disease [LOD]:
      LOD1, 7-26 days; LOD2, 27-89 days), and infants aged 3 months to 1 year (infant
      disease). Results: Among 848 GBS meningitis cases from 2001 to 2014, the
      incidence of EOD decreased by 63.3% (95% confidence interval [CI], 43.9%-80.1%];
      P < .001) and that of LOD increased by 58.1% (95% CI, 39.1%-75.5%); P < .001)
      (52.9% and 64.3% for LOD1 and LOD2, respectively). The mean gestational age (GA)
      decreased significantly for EOD, LOD1, LOD2, and infant disease cases (38.7,
      38.6, 37.3, and 34 weeks, respectively). Serotype III accounted for 83.9% of
      cases, with no significant difference among the 4 groups or by GA. The frequency
      of GBS belonging to the clonal complex 17 did not differ among the 4 groups. Case
      mortality was 11.4%. Conclusions: In the era of intravenous antibiotic
      prophylaxis, we found decreased incidence of early-onset GBS meningitis but,
      unexpectedly, increased incidence of LOD. These data underline the interest in
      the development of effective GBS vaccines for pregnant women.

PMID- 29045605
TI  - Diagnostics for Yaws Eradication: Insights From Direct Next-Generation Sequencing
      of Cutaneous Strains of Treponema pallidum.
AB  - Background: Yaws-like chronic ulcers can be caused by Treponema pallidum
      subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To
      permit accurate evaluation of yaws elimination efforts, programmatic use of
      molecular diagnostics is required. The accuracy and sensitivity of current tools
      remain unclear because our understanding of T. pallidum diversity is limited by
      the low number of sequenced genomes. Methods: We tested samples from patients
      with suspected yaws collected in the Solomon Islands and Ghana. All samples were
      from patients whose lesions had previously tested negative using the Centers for
      Disease Control and Prevention (CDC) diagnostic assay in widespread use. However,
      some of these patients had positive serological assays for yaws on blood. We used
      direct whole-genome sequencing to identify T. pallidum subsp pertenue strains
      missed by the current assay. Results: From 45 Solomon Islands and 27 Ghanaian
      samples, 11 were positive for T. pallidum DNA using the species-wide quantitative
      polymerase chain reaction (PCR) assay, from which we obtained 6 previously
      undetected T. pallidum subsp pertenue whole-genome sequences. These show that
      Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades.
      These isolates were invisible to the CDC diagnostic PCR assay, due to sequence
      variation in the primer binding site. Conclusions: Our data double the number of
      published T. pallidum subsp pertenue genomes. We show that Solomon Islands
      strains are undetectable by the PCR used in many studies and by health
      ministries. This assay is therefore not adequate for the eradication program.
      Next-generation genome sequence data are essential for these efforts.

PMID- 29045607
TI  - Reply to Kenyon.

PMID- 29045608
TI  - Making it back to base: how recruitment to cohort studies affects outcomes.

PMID- 29045609
TI  - Stakeholder Perspectives on the Optimizing Patient Transfers, Impacting Medical
      Quality, and Improving Symptoms: Transforming Institutional Care (OPTIMISTIC)
      Project.
AB  - Background and Objectives: The need to reduce burdensome and costly
      hospitalizations of frail nursing home residents is well documented. The
      Optimizing Patient Transfers, Impacting Medical Quality, and Improving Symptoms:
      Transforming Institutional Care (OPTIMISTIC) project achieved this reduction
      through a multicomponent collaborative care model. We conducted an implementation
      focused project evaluation to describe stakeholders' perspectives on (a) the most
      and least effective components of the intervention; (b) barriers to
      implementation; and (c) program features that promoted its adoption. Research
      Design and Methods: Nineteen nursing homes participated in OPTIMISTIC. We
      conducted semistructured, qualitative interviews with 63 stakeholders: 23 nursing
      home staff and leaders, 4 primary care providers, 10 family members, and 26
      OPTIMISTIC clinical staff. We used directed content analysis to analyze the data.
      Results: We found universal endorsement of the value of in-depth advance care
      planning (ACP) discussions in reducing hospitalizations and improving care.
      Similarly, all stakeholder groups emphasized that nursing home access to
      specially trained, project registered nurses (RNs) and nurse practitioners (NPs)
      with time to focus on ACP, comprehensive resident assessment, and staff education
      was particularly valuable in identifying residents' goals for care. Challenges to
      implementation included inadequately trained facility staff and resistance to
      changing practice. In addition, the program sometimes failed to communicate its
      goals and activities clearly, leaving facilities uncertain about the OPTIMISTIC
      clinical staff's roles in the facilities. Discussion and Implications: These
      findings are important for dissemination efforts related to the OPTIMISTIC care
      model and may be applicable to other innovations in nursing homes.

PMID- 29045610
TI  - High-sensitivity cardiac troponin I and risk of heart failure in patients with
      suspected acute coronary syndrome: a cohort study.
AB  - Aims: Heart failure may occur following acute myocardial infarction, but with the
      use of high-sensitivity cardiac troponin assays we increasingly diagnose patients
      with minor myocardial injury. Whether troponin concentrations remain a useful
      predictor of heart failure in patients with acute coronary syndrome is uncertain.
      Methods and results: We identified all consecutive patients (n = 4748) with
      suspected acute coronary syndrome (61 +/- 16 years, 57% male) presenting to three
      secondary and tertiary care hospitals. Cox-regression models were used to
      evaluate the association between high-sensitivity cardiac troponin I
      concentration and subsequent heart failure hospitalization. C-statistics were
      estimated to evaluate the predictive value of troponin for heart failure
      hospitalization. Over 2071 years of follow-up there were 83 heart failure
      hospitalizations. Patients with troponin concentrations above the upper reference
      limit (URL) were more likely to be hospitalized with heart failure than patients
      below the URL (118/1000 vs. 17/1000 person years, adjusted hazard ratio: 7.0).
      Among patients with troponin concentrations <URL the rate of heart failure
      hospitalization was 2.80-fold higher [95% confidence interval (95% CI 1.81-4.31)]
      per doubling of troponin concentration. On adding troponin to a model with
      demographic, cardiovascular risk factor, and clinical variables, the prediction
      of heart failure hospitalization improved considerably (C-statistic 0.80 vs.
      0.86, P < 0.001). Conclusion: Cardiac troponin is an excellent predictor of heart
      failure hospitalization in patients with suspected acute coronary syndrome. The
      strongest associations were observed in patients with troponin concentrations in
      the normal reference range, in whom high-sensitivity cardiac troponin assays
      identify those at increased risk of heart failure who may benefit from further
      investigation and treatment.

PMID- 29045611
TI  - Cardiovascular disease burden in cancer patients from 2003 to 2014.

PMID- 29045612
TI  - Fractional flow reserve and myocardial perfusion by computed tomography: a guide
      to clinical application.
AB  - The aim of this paper is to provide a guide to the clinical application of the
      functional computed tomography (CT) techniques fractional flow reserve (CT FFR)
      and myocardial perfusion (CTP) in patients presenting for the evaluation of
      coronary artery disease (CAD). Both techniques have recently been introduced to
      complement coronary CT angiography (CTA) with physiological information. Evidence
      supporting their diagnostic accuracy accumulates at a fast pace, and both
      techniques are moving from research tools to clinical applications for specific
      subgroups of patients. As a consequence, the question that now emerges is how to
      optimally implement these techniques in the daily clinical workflow to maximize
      the benefit to patients. Given the inherent differences between both techniques
      in their underlying physical principles and methodology, as well as the types of
      pathophysiological information they provide, these techniques are not
      interchangeable. Rather, within the broad spectrum of patients presenting for CAD
      evaluation, both CT FFR and CTP may have their own optimized application where
      the highest benefit at the lowest risk and cost may be achieved. Therefore, we
      will review the physical principles and available clinical evidence of each
      technique, and propose how this information can be applied to the individual
      patient. Moreover, as techniques continue to mature, the combination of coronary
      CTA with CT FFR and/or CTP likely will become a powerful and accessible
      diagnostic tool for the detailed characterization of atherosclerotic disease
      providing a potentially more precise and personalized approach to patients with
      suspected CAD.

PMID- 29045614
TI  - "I Have to Listen to This Old Body": Femininity and the Aging Body.
AB  - Background and Objectives: This study explores how older women with low
      socioeconomic status living in rural Tanzania give meaning to their (aging) body
      in relation to the ideals of femininity. Research Design and Methods: Ten
      qualitative in-depth interviews and 10 focus group discussions (N = 60) were
      conducted among women aged 60 and older. Results: The findings reveal that older
      women perceive their aging body as "a burden." This characterization of the body
      is linked to the inability of the aging body to live up to the women's gendered
      lives. The conflict between their physical limitations and the desire to perform
      gendered tasks (internalized feminine habitus) affect the women's process of self
      identification. This led to emotional distress and subsequently threatened their
      survival and well-being. Discussion and Implications: The results suggest that
      older women need to be supported through interventions that are tailored to their
      cultural and socioeconomic context.

PMID- 29045613
TI  - Genome structure of Rosa multiflora, a wild ancestor of cultivated roses.
AB  - The draft genome sequence of a wild rose (Rosa multiflora Thunb.) was determined
      using Illumina MiSeq and HiSeq platforms. The total length of the scaffolds was
      739,637,845 bp, consisting of 83,189 scaffolds, which was close to the 711 Mbp
      length estimated by k-mer analysis. N50 length of the scaffolds was 90,830 bp,
      and extent of the longest was 1,133,259 bp. The average GC content of the
      scaffolds was 38.9%. After gene prediction, 67,380 candidates exhibiting sequence
      homology to known genes and domains were extracted, which included complete and
      partial gene structures. This large number of genes for a diploid plant may
      reflect heterogeneity of the genome originating from self-incompatibility in R.
      multiflora. According to CEGMA analysis, 91.9% and 98.0% of the core eukaryotic
      genes were completely and partially conserved in the scaffolds, respectively.
      Genes presumably involved in flower color, scent and flowering are assigned. The
      results of this study will serve as a valuable resource for fundamental and
      applied research in the rose, including breeding and phylogenetic study of
      cultivated roses.

PMID- 29045615
TI  - Superadditive and Subadditive Neural Processing of Dynamic Auditory-Visual
      Objects in the Presence of Congruent Odors.
AB  - Our sensory experiences comprise a variety of different inputs at any given time.
      Some of these experiences are unmistakable, others are ambiguous and profit from
      additional sensory information. Here, we explored whether the presence of a
      congruent odor influences the neural processing and sensory interaction of audio
      visual objects using degraded videos (V) and sounds (A) of dynamic objects in
      unimodal and bimodal (AV) combinations without or with a congruent odor (VO, AO,
      AVO). Analyses of EEG data revealed superadditive and subadditive interaction
      effects. The topography and timing of these effects suggest evaluative rather
      than sensory processes as the underlying cause. Together, the results suggest
      that the mere presence of an odor affects the processing of A, V, and AV objects
      differently while multisensory interactions of AV and AVO objects have common
      neuronal mechanisms pointing to a robust, modality-independent network for the
      processing of redundant sensory information.

PMID- 29045616
TI  - Potential impact of global climate change on benthic deep-sea microbes.
AB  - Benthic deep-sea environments are the largest ecosystem on Earth, covering ~65%
      of the Earth surface. Microbes inhabiting this huge biome at all water depths
      represent the most abundant biological components and a relevant portion of the
      biomass of the biosphere, and play a crucial role in global biogeochemical
      cycles. Increasing evidence suggests that global climate changes are affecting
      also deep-sea ecosystems, both directly (causing shifts in bottom-water
      temperature, oxygen concentration and pH) and indirectly (through changes in
      surface oceans' productivity and in the consequent export of organic matter to
      the seafloor). However, the responses of the benthic deep-sea biota to such
      shifts remain largely unknown. This applies particularly to deep-sea microbes,
      which include bacteria, archaea, microeukaryotes and their viruses. Understanding
      the potential impacts of global change on the benthic deep-sea microbial
      assemblages and the consequences on the functioning of the ocean interior is a
      priority to better forecast the potential consequences at global scale. Here we
      explore the potential changes in the benthic deep-sea microbiology expected in
      the coming decades using case studies on specific systems used as test models.

PMID- 29045617
TI  - Purification of Four Flavonoid Glycosides from Lotus (Nelumbo nucifera Gaertn)
      plumule by Macroporous Resin Combined with HSCCC.
AB  - High-speed counter-current chromatography (HSCCC) combined with macroporous resin
      (MR) column was successfully applied to the isolation and purification of four
      flavonoid glycosides from the medicinal herb Lotus plumule (LP). A polar two
      phase solvent system composed of ethyl acetate-n-butanol-water (1:2:3, v/v/v) was
      selected by high-performance liquid chromatography (HPLC) and run on a
      preparative scale where the lower aqueous phase was used as the mobile phase with
      a head-to-tail elution mode. Quercetin-3-O-beta-D-glucopyranoside (15 mg),
      isorhamnetin-3-O-beta-D-glucopyranoside (13 mg), apigenin 6-C-beta-D
      glucopyranosyl-8-C-alpha-L-arabinopyranoside (18 mg) and apigenin 6,8-di-C-beta-D
      glucopyranoside (48 mg) were obtained in a one-step HSCCC separation from 240 mg
      of the sample. The purity of each compound was over 95% as determined by HPLC.
      Chemical structures of the isolated compounds were identified by electrospray
      ionization mass spectrometry (ESI-MS-MS) and nuclear magnetic resonance (NMR)
      methods. Moreover, the four compounds were isolated from LP for the first time.

PMID- 29045618
TI  - CD27 co-stimulation increases the abundance of regulatory T cells and reduces
      atherosclerosis in hyperlipidaemic mice.
AB  - Aims: The co-stimulatory receptor CD27 modulates responses of T cells, B cells,
      and NK cells. Various T cell subsets participate in atherogenesis. However, the
      role of CD27 in atherosclerosis remains unexplored. Methods and results: Here we
      investigated the effect of bone marrow-derived and systemic CD27 deficiency in
      Apolipoprotein E-deficient (Apoe-/-) mice in early and advanced stages of
      atherosclerosis. Lethally-irradiated Apoe-/- mice reconstituted with Cd27-/-Apoe
      /- bone marrow and consuming an atherogenic diet displayed a markedly increased
      plaque size and lesional inflammation compared to mice receiving Cd27+/+Apoe-/-
      bone marrow. Accordingly, chow diet-fed Cd27-/-Apoe-/- mice showed exacerbated
      lesion development and increased inflammation at the age of 18 weeks. At a more
      advanced stage of atherosclerosis (28 weeks), lesion size and phenotype did not
      differ between the two groups. Systemic and bone marrow-derived CD27 deficiency
      reduced the abundance of regulatory T cells (Treg) in blood, lymphoid organs, and
      the aorta. Numbers of other immune cells were not affected while expression of
      inflammatory cytokine genes (e.g. IL-1beta and IL-6) was increased in the aorta
      when haematopoietic CD27 was lacking. In vitro, Tregs of CD27-deficient mice
      showed similar suppressive capacity compared with their wild-type controls and
      migrated equally towards CCL19 and CCL21. However, thymic Cd27-/- Tregs underwent
      increased apoptosis and expressed fewer markers of proliferation in vivo.
      Reconstitution of Cd27-/-Apoe-/- mice with Cd27+/+Apoe-/- Tregs reversed the
      increase in atherosclerosis. Conclusion: We demonstrate that CD27 co-stimulation
      increases the number of Tregs and limits lesion development and inflammation in
      experimental atherosclerosis, particularly during early stages of disease. Thus,
      our study suggests that promotion of CD27 function may mitigate atherosclerosis.

PMID- 29045619
TI  - Family practice goes online.

PMID- 29045621
TI  - Using proton pump inhibitors correlates with an increased risk of chronic kidney
      disease: a nationwide database-derived case-controlled study.
AB  - Background: Those taking proton pump inhibitors (PPIs) might have a higher risk
      of acute kidney injury. The long-term safety, especially the PPI-associated
      chronic kidney disease (CKD) is the subsequent concern. Objective: This study
      explores the potential relationship between using PPIs and CKD in Taiwan.
      Methods: Using a database collated by the Taiwan National Health Insurance
      programme, we conducted a population-based case-controlled study to identify 16
      704 cases of patients aged 20 years or older with newly diagnosed CKD between
      2000 and 2013. 16 704 controls were randomly selected and were matched by sex,
      age and comorbidities. 'Use' of PPIs was defined as when subjects had received at
      least a prescription for PPIs before the index date. 'Non-use' was defined as
      subjects who had never received a prescription for PPIs before the index date.
      The odds ratio (OR) for CKD associated with the use of PPIs was estimated by a
      logistic regression model. Results: The OR for CKD was 1.41 for subjects using
      PPIs [95% confidence interval (CI) 1.34, 1.48] compared with subjects who had
      never used PPIs. Almost all major types of PPIs present a weak association with
      increased odds of CKD in cumulative duration and dosage regression analysis. The
      OR in relation to cumulative duration (per month) of PPIs use was 1.02 (95% CI
      1.01, 1.02) and the OR in relation to cumulative dosage (per microgram) of PPIs
      use was 1.23 (95% CI 1.18, 1.28). Conclusions: Using PPIs presented 1.4-fold
      higher odds of CKD in Taiwan health insurance claims data analysis.

PMID- 29045620
TI  - Determination and Pharmacokinetics of WGA in Rat Plasma by LC-MS After Oral
      Administration of Xanthoceras sorbifolia Bunge Extract.
AB  - 3-O-(3-O-angeloyl-6-O-beta-D-glucopyranosyl)-beta-D-glucopyranosyl-28-O-(2-alpha
      L-rhamnopyranosyl-6-O-beta-D-glucopyranosyl)-beta-D-glucopyranosyl-16
      deoxybarringtogenol A (WGA) is a potential anti-AD (Alzheimer's disease) active
      compound isolated from the husks of Xanthoceras sorbifolia Bunge. A rapid and
      accurate high-performance liquid chromatography-mass spectrometry (LC-MS) method
      was developed and validated for the quantification of WGA in rat plasma. Digoxin
      was used as internal standard (IS). Sample preparation was performed by liquid
      liquid extraction using ethyl acetate-isopropanol (1:1, v/v). HPLC separation was
      carried out using a Venusil MP C18 column (150 mm * 4.6 mm, 5 MUm). Isocratic
      elution was performed using methanol: water (70:30, v/v) as the mobile phase, at
      a flow rate of 0.8 mL/min. Analysis was performed in selected ion monitoring mode
      with a positive electrospray ionization interface. No endogenous interference was
      observed at the retention time of the analyte because of the high specificity of
      selected ion monitoring mode. The assay was validated to demonstrate the
      selectivity, linearity, recovery, accuracy, precision and stability. The lower
      limit of quantification (LLOQ) was 10.0 ng/mL. The developed and validated method
      has been successfully applied to the quantification and pharmacokinetic study of
      WGA in rats after oral administration of X. sorbifolia Bunge extract.

PMID- 29045622
TI  - International exchanges in primary care-learning from thy neighbour.
AB  - This systematic review describes how international exchange programmes in primary
      care have been received and evaluated. Electronic databases (MEDLINE, Embase,
      PsycINFO, EBM reviews, CAB abstracts and PubMED) were searched to identify
      articles where the main focus of the study was exchanges undertaken in primary
      care/family medicine until March 2016. Articles were included if they (i)
      discussed participant exchanges in primary care; (ii) presented associated
      outcome data-this included (a) individual/group experience of exchange; (b)
      mechanism of exchange and (c) observations during the exchange. A narrative
      synthesis was performed of the heterogeneous data identified. Twenty-nine studies
      were included. Exchange locations varied across the world with the largest number
      in Europe. Participants came from a range of backgrounds including medical
      students, nurses, General Practitioners (GP), GP trainees (GPTs) and visiting
      scholars/professors. Exchange duration ranged from 3 days to 2 years. Key themes
      were identified from analysis of the studies with illustrative quotes from the
      included studies provided. Four key areas were discussed in relation to exchange
      experience: learning opportunities and new knowledge; comparative observation;
      knowledge gained and translational learning. Primary care international exchanges
      provide a rich source of cross-country learning. This review identified that
      exchange participants benefit both personally and professionally, equipping them
      with translatable skills to improve the care provided to their patients.

PMID- 29045623
TI  - The Influence of Circadian Timing on Olfactory Sensitivity.
AB  - Olfactory sensitivity has traditionally been viewed as a trait that varies
      according to individual differences but is not expected to change with one's
      momentary state. Recent research has begun to challenge this position and time of
      day has been shown to alter detection levels. Links between obesity and the
      timing of food intake further raise the issue of whether odor detection may vary
      as a function of circadian processes. To investigate this question, 37 (21 male)
      adolescents (M age = 13.7 years) took part in a 28-h forced desynchrony (FD)
      protocol with 17.5 h awake and 10.5 h of sleep, for 7 FD cycles. Odor threshold
      was measured using Sniffin' Sticks 6 times for each FD cycle (total threshold
      tests = 42). Circadian phase was determined by intrinsic period derived from dim
      light melatonin onsets. Odor threshold showed a significant effect of circadian
      phase, with lowest threshold occurring on average slightly after the onset of
      melatonin production, or about 1.5? (approximately 21:08 h). Considerable
      individual variability was observed, however, peak olfactory acuity never
      occurred between 80.5? and 197.5? (~02:22-10:10 h). These data are the first to
      show that odor threshold is differentially and consistently influenced by
      circadian timing, and is not a stable trait. Potential biological relevance for
      connections between circadian phase and olfactory sensitivity are discussed.

PMID- 29045625
TI  - Coronary optical coherence tomography-derived virtual fractional flow reserve
      (FFR): anatomy and physiology all-in-one.

PMID- 29045624
TI  - Long-term cell culture isolated from lesions of mice infected with Leishmania
      amazonensis: a new approach to study mononuclear phagocyte subpopulations during
      the infection.
AB  - Leishmanioses are neglected diseases and the parasite Leishmania survives and
      proliferates within mononuclear phagocytes, particularly macrophages. In vitro
      studies of the immunology and cell biology of leishmaniosis are performed in
      murine peritoneum and bone marrow macrophages and immortalized cell lines despite
      the normal and injured tissue-specific heterogeneity of macrophages. In this
      work, we established an ex vivo methodology to culture lesional cells from BALB/c
      mice infected with Leishmania amazonensis. The cells were successfully isolated
      from footpad skin lesions and those exhibiting macrophage morphology were
      maintained in long-term culture (12 days), while the small number of lymphocytes,
      polymorphonuclear and unidentified cells died after 1 day of culture. The
      frequency of infected cells decreased over 2 days. Most lesional cells cultivated
      ex vivo were myeloid CD11b+ CD14+ F4/80+ CD68+ cells. Low levels of IFN-gamma and
      IL-4, IL-10 production and low arginase and phagocytic activities were detected
      in ex vivo lesional cell cultures. The ex vivo model developed in this study open
      perspectives for studying the biology of leishmanial lesions in cellular
      subpopulations and at the single-cell level.

PMID- 29045627
TI  - Corrigendum to: Global position paper on cardiovascular regenerative medicine.

PMID- 29045626
TI  - Primary and heterotrophic productivity relate to multikingdom diversity in a
      hypersaline mat.
AB  - Benthic microbial ecosystems are widespread yet knowledge gaps still remain on
      the relationships between the diversity of species across kingdoms and
      productivity. Here, we ask two fundamental questions: (i) How does species
      diversity relate to the rates of primary and heterotrophic productivity? (ii) How
      do diel variations in light-energy inputs influence productivity and microbiome
      diversity? To answer these questions, microbial mats from a magnesium sulfate
      hypersaline lake were used to establish microcosms. Both the number and
      relatedness between bacterial and eukaryotic taxa in the microbiome were assayed
      via amplicon-based sequencing of 16S and 18S rRNA genes over two diel cycles.
      These results correlated with biomass productivity obtained from substrate
      specific 13C stable isotope tracers that enabled comparisons between primary and
      heterotrophic productivity. Both bacterial and eukaryotic species richness and
      evenness were related only to the rates of 13C-labeled glucose and acetate
      biomass incorporation. Interestingly, measures of these heterotrophic
      relationships changed from positive and negative correlations depending on carbon
      derived from glucose or acetate, respectively. The bacterial and eukaryotic
      diversity of this ecosystem is also controlled, in part, from energy constraints
      imposed by changing irradiance over a diel cycle.

PMID- 29045628
TI  - Troponin measurement in patients with suspected acute coronary syndromes: walking
      beyond the wall.

PMID- 29045629
TI  - Signs and symptoms of Group A versus Non-Group A strep throat: A meta-analysis.
AB  - Introduction: Both non-Group A streptococcal (non-GAS) pharyngitis and Group A
      streptococcal (GAS) pharyngitis are commonly found in patients with sore throat.
      It is not known whether or not they present with similar signs and symptoms
      compared to patients with non-streptococcal pharyngitis. Methods: MEDLINE was
      searched for prospective studies that reported throat culture for both GAS and
      non-GAS as a reference standard, and reported at least one sign, symptom, or the
      Centor score. Summary estimates of sensitivity, specificity, likelihood ratios
      (LR+ and LR-), and diagnostic odds ratios (DOR) were calculated using a bivariate
      random effects model. Summary receiver operating characteristic (ROC) curves were
      created for key signs and symptoms. Results: Eight studies met our inclusion
      criteria. Tonsillar exudate had the highest LR+ for both GAS and non-GAS
      pharyngitis (1.53 versus 1.71). The confidence intervals of sensitivity, LR+, LR
      , and DOR for all signs, symptoms, and the Centor score between two groups
      overlapped, with the relative difference between sensitivities within 15% for
      arthralgia or myalgia, fever, injected throat, tonsillar enlargement, and
      tonsillar exudate. Larger differences in sensitivities were observed for sore
      throat, cervical adenopathy, and lack of a cough, although the difference for
      lack of a cough largely due to a single outlier. Discussion: Signs and symptoms
      of patients with GAS and non-GAS pharyngitis are generally similar. No signs or
      symptoms clearly distinguish GAS from non-GAS infection. Further work is needed
      to determine whether Group C streptococcus is a pathogen that should be treated.

PMID- 29045630
TI  - Field Assessments to Control the Lesser Mealworm (Coleoptera: Tenebrionidae)
      Using Diatomaceous Earth in Poultry Houses.
AB  - Control of the lesser mealworm (Alphitobius diaperinus Panzer, 1797 [Coleoptera:
      Tenebrionidae]) is usually conducted with chemical insecticides, which have
      limited efficacy as well as environmental and health risks. Diatomaceous earth
      (DE) is safe and effective in controlling many insects including lesser mealworm.
      However, little is known of DE efficacy against this pest. Thus, an assessment of
      DE was conducted for the first time in commercial broiler houses in Brazil, with
      the aim of developing a strategy for the use of DE in the control of this insect.
      The efficacy of DE was determinate to a minimum concentration, and the
      application was directed to the most infested sites. The DE applied to the entire
      poultry house (280 g/m2) was verified to control the insects. DE was also
      comparable to chemical treatments, with a reduction of 80% in the insect
      population. DE controlled the lesser mealworm and is recommended for application
      at a concentration of 280 g/m2 when applied to the surface of new poultry litter,
      before the first lot of birds is housed. Thereafter, DE should be reapplied
      before the housing of each lot of birds, in the same concentration, only in the
      housing area and under the feeders and near the walls and pillars. In addition to
      being a control strategy, DE can be an important tool in the management of lesser
      mealworm insecticide resistance.

PMID- 29045631
TI  - Implementation of Advance Care Planning in Israel: A Convergence of Top-Down and
      Bottom-Up Processes.
AB  - Although public health has traditionally been concerned with primary, secondary,
      and tertiary prevention, more attention needs to be focused on patient-centered
      care at the end of life. Improved access to quality end-of-life care can be
      achieved by advance care planning (ACP). In this article, we present an example
      of the processes of change regarding ACP and preparing advance directives (ADs)
      that have begun to take place in Israel in recent years. We argue that these
      processes derive from the synergy between legislation on the one hand, and
      initiatives and action by health organizations on the other. In other words, top
      down action such as legislation and directives issued by the Ministry of Health
      in the past decade, alongside bottom-up action in the health plans and other
      organizations, have led to change that could not have happened without either
      side. In the first part of the article, we present Israel's Dying Patient Act and
      its ensuing amendments and in the second part, we present examples of activities
      in the health services. In the third part of the article, we discuss the argument
      that it is only thanks to the combination of top-down and bottom-up action that a
      breakthrough has been achieved.

PMID- 29045632
TI  - Patient, general practitioner and oncologist views regarding long-term cancer
      shared care.
AB  - Background: The rising incidence of cancer and increasing number of cancer
      survivors place competing demands on specialist oncology clinics. This has led to
      a need to consider collaborative care between primary and secondary care for the
      long-term post-treatment care of cancer survivors. Objective: To explore the
      views of breast and colorectal cancer survivors, their oncologist and GP about
      GPs taking a more active role in long-term cancer follow-up care. Methods: Semi
      structured interviews using a thematic analysis framework. Respondents were asked
      their views on the specialist hospital-based model for cancer follow-up care and
      their views on their GP taking a greater or leading role in follow-up care.
      Researcher triangulation was used to refine the coding framework and emergent
      themes; source triangulation and participant validation were used to increase
      credibility. Results: Fifty-six interviews were conducted (22 patients, 16
      oncologists, 18 GPs). Respondents highlighted the importance of GPs needing
      specialist cancer knowledge; the need for GPs to have an interest in and time for
      cancer follow-up care; the GPs role in providing psychosocial care; and the
      reassurance that was provided from a specialist overseeing care. A staged, shared
      care team arrangement with both GPs and specialists flexibly providing continuing
      care was found to be acceptable for most. Conclusion: Collaborative care of
      cancer survivors may lessen the load on specialist oncology clinics. The findings
      suggest that building this model will require early and ongoing shared care
      processes.

PMID- 29045633
TI  - Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic
      review of risk factors in clinical practice.
AB  - Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency
      of alpha-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of
      mortality in FD, in particular as a result of heart failure and arrhythmia, with
      a significant proportion of events categorized as sudden. There are no clear
      models for risk prediction in FD. This systematic review aims to identify the
      risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in
      FD. A systematic search was performed following PRISMA guidelines of EMBASE,
      Medline, PubMed, Web of Science, and Cochrane from inception to August 2016,
      focusing on identification of risk factors for the development of VA or SCD.
      Thirteen studies were included in the review (n = 4185 patients) from 1189
      articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years,
      and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was
      due to CV problems, with the majority being SCD events (62% of reported deaths).
      Ventricular tachycardia was reported in 7 studies, with an average prevalence of
      15.3%. Risk factors associated with SCD events were age, male gender, left
      ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance
      imaging, and non-sustained ventricular tachycardia. Although a multi-system
      disease, FD is a predominantly cardiac disease from a mortality perspective, with
      death mainly from SCD events. Limited evidence highlights the importance of
      clinical and imaging risk factors that could contribute to improved decision
      making in the management of FD.

PMID- 29045634
TI  - Does CHA2DS2-VASc score predict ischaemic stroke in chronic obstructive pulmonary
      disease?

PMID- 29045635
TI  - Caregiving Spouses and the Experience of Involuntary Separation.
AB  - Background and Objectives: We explored the meaning of the experience of
      involuntary separation, as defined formally by the Canadian government and
      informally by our participants, in formerly caregiving spouses whose partners had
      been admitted to long-term care. Our goal was to explore their lifeworld
      experience of separation, including factors influencing well-being as spouses
      shifted from at-home caregiving to involuntary separation. Research Design and
      Methods: Guided, semi-scripted personal interviews were conducted with 10
      individuals who had become involuntarily separated up to 4 years prior to the
      interview. A psychological-phenomenological analysis of participant narratives
      was conducted following procedures set out by Giorgi (2009). Results: Themes
      included access and continued involvement with spouse post-admission; seeking
      connections with family, friends, and spiritual resources; adaptability in the
      face of change and loss; and the immediate and long-term emotional impact of
      involuntary separation. Regular involvement with spouses, resources and
      connections with others, and adaptability contributed to well-being, but the
      experience was nonetheless described as an "emotional bomb." Discussion and
      Implications: Participants experienced involuntary separation as an overwhelming
      burden marked by ongoing losses, from connections with spouses and social
      supports to shifts in identity and financial security. Greater understanding of
      the unique needs and experiences of involuntarily separated spouses may help
      individuals cope in practical ways with their shifting situation and highlights
      the value of meaning-focused support.

PMID- 29045636
TI  - The diagnostic accuracy of the Ascertain Dementia 8 questionnaire for detecting
      cognitive impairment in primary care in the community, clinics and hospitals: a
      systematic review and meta-analysis.
AB  - Background: The prevalence of cognitive impairment is increasing due to the aging
      population, and early detection is essential clinically. The Ascertain Dementia 8
      (AD8) questionnaire is a brief informant-based measure recently developed to
      assess early cognitive impairment, however, its overall diagnostic performance is
      controversial. The objective of this meta-analysis was to assess the diagnostic
      accuracy of the AD8 for cognitive impairment. Methods: All relevant studies were
      collected from databases including MEDLINE, EMBASE and the Cochrane Library up to
      April 2017. We used QUADAS-2 to assess the methodological quality after the
      systematic search. The accuracy data and potential confounding variables were
      extracted from the eligible studies which included those in English and non
      English. All analyses were performed using the Midas module in Stata 14.0 and
      Meta-DiSc 1.4 software. Results: Seven relevant studies including 3728 subjects
      were collected, and classified into two subgroups according to the severity of
      cognitive impairment. The overall sensitivity (0.72, 0.91) was superior to
      specificity (0.67, 0.78). The pooled negative likelihood ratio (0.17, 0.13) was
      better than the positive likelihood ratio (2.52, 3.94). The areas under the
      summary receiver operating characteristic curve were 0.83 and 0.92, respectively.
      Meta-regression analysis showed that location (community versus non-community)
      may be the source of heterogeneity. The average administration time was less than
      3 minutes. Conclusion: Our findings suggest that the AD8 is a competitive tool
      for clinically screening cognitive impairment and has an optimal administration
      time in the busy primary care setting. Subjects with an AD8 score ?2 should be
      highly suspected to have cognitive impairment and a further definite diagnosis is
      needed.

PMID- 29045637
TI  - Effects of Feeding on Different Host Plants and Diets on Bradysia Odoriphaga
      Population Parameters and Tolerance to Heat and Insecticides.
AB  - Bradysia odoriphaga Yang et Zhang, the Chinese chive root maggot, is a
      devastating pest of agricultural plants causing significant losses in vegetable
      crops, edible mushrooms, and humus. To determine the effects of feeding on
      different host plants and diets on the life parameters of B. odoriphaga and its
      tolerance to stressful conditions, we analyzed the life-table data of B.
      odoriphaga reared on Chinese chive (Allium hookeri), Welsh onion (Allium
      fistulosum), garlic (Allium sativum), oyster mushroom (Pleurotus ostreatus), and
      humus and assayed its tolerance to heat and insecticides. Furthermore, we assayed
      the physiological responses of B. odoriphaga reared on different hosts.
      Development from egg to adult was successfully completed on five hosts. Life
      table indicated that when reared on Chinese chive and oyster mushroom, B.
      odoriphaga showed better life parameters (shorter development time, higher
      survival rate, and fecundity) than on humus and garlic. However, B. odoriphaga
      larvae fed on humus and garlic better tolerated heat and insecticides than those
      that were fed Chinese chive and oyster mushroom; larvae survived longer at 38 and
      40 degrees C heat shock and at higher insecticide doses. Activities of
      antioxidant and detoxification enzymes varied significantly in larvae fed on
      different hosts. Catalase, superoxide dismutase, glutathione S-transferase, and
      carboxylesterase activities were higher in larva reared on garlic and humus than
      on Chinese chive and oyster mushroom. These findings indicated that B. odoriphaga
      preferred liliaceous vegetables and mushroom, and their tolerance against stress
      increased when reared on humus and garlic. Such basic information can promote
      targeted pest management in different agricultural fields and allow better
      understanding of the acclimatization strategy of B. odoriphaga.

PMID- 29045639
TI  - A New Perspective on Polyploid Fragaria (Strawberry) Genome Composition Based on
      Large-Scale, Multi-Locus Phylogenetic Analysis.
AB  - The subgenomic compositions of the octoploid (2n = 8* = 56) strawberry (Fragaria)
      species, including the economically important cultivated species Fragaria x
      ananassa, have been a topic of long-standing interest. Phylogenomic approaches
      utilizing next-generation sequencing technologies offer a new window into species
      relationships and the subgenomic compositions of polyploids. We have conducted a
      large-scale phylogenetic analysis of Fragaria (strawberry) species using the
      Fluidigm Access Array system and 454 sequencing platform. About 24 single-copy or
      low-copy nuclear genes distributed across the genome were amplified and sequenced
      from 96 genomic DNA samples representing 16 Fragaria species from diploid (2*) to
      decaploid (10*), including the most extensive sampling of octoploid taxa yet
      reported. Individual gene trees were constructed by different tree-building
      methods. Mosaic genomic structures of diploid Fragaria species consisting of
      sequences at different phylogenetic positions were observed. Our findings support
      the presence in octoploid species of genetic signatures from at least five
      diploid ancestors (F. vesca, F. iinumae, F. bucharica, F. viridis, and at least
      one additional allele contributor of unknown identity), and questions the extent
      to which distinct subgenomes are preserved over evolutionary time in the
      allopolyploid Fragaria species. In addition, our data support divergence between
      the two wild octoploid species, F. virginiana and F. chiloensis.

PMID- 29045640
TI  - Action potential contour contributes to species differences in repolarization
      response to beta-adrenergic stimulation.
AB  - Aim: Repolarization response to beta-adrenergic (beta-AR) stimulation differs
      between guinea-pig and canine myocytes and, within the latter, between myocardial
      layers. Correlative analysis suggests that this may be due to differences in
      action potential (AP) contour. Here we tested whether AP contour may set the
      response of current and of repolarization to beta-AR stimulation (10 nM
      isoproterenol, ISO). Methods and results: The responses of AP and current to ISO
      were measured under I-clamp and "AP-clamp" in guinea-pig (GP), dog epicardial
      (DEPI) and dog subendocardial (DENDO) myocytes. Dynamic-clamp (DC) was used to
      evaluate the impact of AP features on AP response to ISO. ISO prolonged AP
      duration (APD) in GP myocytes, did not affect it in DENDO and shortened it in
      DEPI ones. The current induced by ISO (IISO) sharply differed between GP and
      canine myocytes and, to a lesser extent, between DENDO and DEPI ones. Differences
      in IISO profile likely important in setting APD response (time-to-peak, time-to
      reversal), were minimized when canine myocytes where clamped with GP AP-waveforms
      and vice versa. Introduction of a "notch" in GP AP (by DC) was alone insufficient
      to affect the APD response to ISO; nevertheless, when incorporated in a GP AP
      waveform, the main "canine" AP features ("notch" and low plateau potential)
      caused IISO of GP myocytes to acquire canine features. Conclusion: Early
      repolarization contour and level of plateau potential contribute to species
      specificity of IISO profile. Changes in AP contour, also when generated by
      modulation of ISO-insensitive currents, may be crucial in setting APD response to
      beta-AR stimulation.

PMID- 29045641
TI  - Genetic Variability of Two Leaffooted Bugs, Leptoglossus clypealis and
      Leptoglossus zonatus (Hemiptera: Coreidae) in the Central Valley of California.
AB  - Leaffooted plant bugs (LFPBs) (Leptoglossus spp., Guerin-Meneville) (Hemiptera:
      Coreidae) are large seed-feeding bugs native to the Western Hemisphere. In
      California, several Leptoglossus spp. feed on almonds, pistachios, and
      pomegranate and are occasional pests. The objective of this study was to survey
      the different species of Leptoglossus present in almond, pistachio, and
      pomegranate orchards in the Central Valley of California. We used two molecular
      markers, amplified fragment length polymorphisms (AFLPs) and mitochondrial DNA
      COI, to determine the number of species or strains of each species, and to infer
      whether individuals of each species move and possibly interbreed with populations
      from the other host plants. Two species of leaffooted bugs were abundant,
      Leptoglossus clypealis Heidemann, and Leptoglossus zonatus (Dallas). L. clypealis
      was collected in almond and pistachio, while L. zonatus was found on all three
      host plants, but was the dominant species in pomegranate. The AFLP results
      indicated that L. clypealis consisted of one species, which suggests it moves
      between almonds and pistachios during the growing season. Mitochondrial DNA COI
      for L. clypealis found 1-2% divergence between sequences, and a high haplotype
      diversity of 0.979 with 17 haplotypes. The AFLP results for L. zonatus found two
      genetically divergent populations which were morphologically similar. The mtDNA
      COI sequences for L. zonatus were used for haplotype analysis; three haplotypes
      were found in California, with one haplotype shared with collections from Brazil.
      The importance of genetic variability and cryptic species for pest management are
      discussed.

PMID- 29045638
TI  - Subversion of nutritional immunity by the pathogenic Neisseriae.
AB  - The pathogenic Neisseria species, including Neisseria meningitidis and Neisseria
      gonorrhoeae, are obligate human pathogens that cause significant morbidity and
      mortality. The success of these pathogens, with regard to causing disease in
      humans, is inextricably linked to their ability to acquire necessary nutrients in
      the hostile environment of the host. Humans deploy a significant arsenal of
      weaponry to defend against bacterial pathogens, not least of which are the metal
      sequestering proteins that entrap and withhold transition metals, including iron,
      zinc and manganese, from invaders. This review will discuss the general
      strategies that bacteria employ to overcome these metal-sequestering attempts by
      the host, and then will focus on the relatively uncommon 'metal piracy'
      approaches utilized by the pathogenic Neisseria for this purpose. Because
      acquiring metals from the environment is critical to microbial survival,
      interfering with this process could impede growth and therefore disease
      initiation or progression. This review will also discuss how interfering with
      metal uptake by the pathogenic Neisseriae could be deployed in the development of
      novel or improved preventative or therapeutic measures against these important
      pathogens.

PMID- 29045643
TI  - Erratum to: 'Current mid-term outcome with an integrated surgical strategy for
      correction of d-transposition of the great arteries with ventricular septal
      defect and left ventricular outflow tract obstruction' [Eur J Cardiothorac Surg
      2016;50(4):617-625; doi:10.1093/ejcts/ezw058].

PMID- 29045642
TI  - Influence of patient and tumor characteristics on early therapy persistence with
      letrozole in postmenopausal women with early breast cancer: results of the
      prospective Evaluate-TM study with 3941 patients.
AB  - Background: Patients' compliance and persistence with endocrine treatment has a
      significant effect on the prognosis in early breast cancer (EBC). The purpose of
      this analysis was to identify possible reasons for non-persistence, defined as
      premature cessation of therapy, on the basis of patient and tumor characteristics
      in individuals receiving adjuvant treatment with letrozole. Patients and methods:
      The EvAluate-TM study is a prospective, multicenter, noninterventional study in
      which treatment with the aromatase inhibitor letrozole was evaluated in
      postmenopausal women with hormone receptor-positive EBC in the early therapy
      phase. Treatment persistence was evaluated at two pre-specified study visits
      after 6 and 12 months. As a measure of early therapy persistence the time from
      the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses
      were carried out to identify patient characteristics and tumor characteristics
      predicting TTEOT. Results: Out of the total population of 3941 patients with EBC,
      540 (13.7%) events involving treatment cessation unrelated to disease progression
      were observed. This was due to drug-related toxicity in the majority of cases
      (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15
      months, respectively. The main factors influencing premature treatment
      discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR
      1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per
      grade unit). Conclusion: These results support the view that older, multimorbid
      patients with low tumor grade and low body mass index are at the greatest risk
      for treatment discontinuation and might benefit from compliance and support
      programs.

PMID- 29045644
TI  - 2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein
      convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic
      cardiovascular disease or in familial hypercholesterolaemia.

PMID- 29045646
TI  - Coming of Age in Aging America.

PMID- 29045645
TI  - Predictors of antimalarial self-medication in illegal gold miners in French
      Guiana: a pathway towards artemisinin resistance.
AB  - Background: Malaria is endemic in French Guiana (FG), South America. Despite the
      decrease in cases in the local population, illegal gold miners are very affected
      by malaria (22.3% of them carried Plasmodium spp.). Self-medication seems to be
      very common, but its modalities and associated factors have not been studied. The
      aim of this study was to evaluate parasite susceptibility to drugs and to
      document behaviours that could contribute to resistance selection in illegal gold
      miners. Methods: This multicentric cross-sectional study was conducted in resting
      sites along the FG-Surinamese border. Participating gold miners working in FG
      completed a questionnaire and provided a blood sample. Results: From January to
      June 2015, 421 illegal gold miners were included. Most were Brazilian (93.8%) and
      70.5% were male. During the most recent malaria attack, 45.5% reported having
      been tested for malaria and 52.4% self-medicated, mainly with artemisinin
      derivatives (90%). Being in FG during the last malaria attack was the main factor
      associated with self-medication (adjusted OR = 22.1). This suggests that access
      to malaria diagnosis in FG is particularly difficult for Brazilian illegal gold
      miners. Treatment adherence was better for persons who reported being tested.
      None of the 32 samples with Plasmodium falciparum presented any mutation on the
      pfK13 gene, but one isolate showed a resistance profile to artemisinin
      derivatives in vitro. Conclusions: The risk factors for the selection of
      resistance are well known and this study showed that they are present in FG with
      persons who self-medicated with poor adherence. Interventions should be
      implemented among this specific population to avoid the emergence of artemisinin
      resistance.

PMID- 29045647
TI  - Mechanical aortic valve replacement in non-elderly adults: meta-analysis and
      microsimulation.
AB  - Aims: To support decision-making regarding prosthetic valve selection in non
      elderly adults, we aim to provide a detailed overview of outcome after
      contemporary mechanical aortic valve replacement (AVR). Methods and results: A
      systematic review was conducted for papers reporting clinical outcome after AVR
      with bileaflet mechanical valves with a mean patient age >=18 and <=55 years,
      published between 1 January 1995 and 31 December 2015. Through meta-analysis
      outcomes were pooled and entered into a microsimulation model to calculate (event
      free) life expectancy and lifetime event risk. Twenty-nine publications,
      encompassing a total of 5728 patients with 32 515 patient-years of follow-up
      (pooled mean follow-up: 5.7 years), were included. Pooled mean age at surgery was
      48.0 years. Pooled early mortality risk was 3.15% (95% confidence interval
      (CI):2.37-4.23), late mortality rate was 1.55%/year (95%CI:1.25-1.92); 38.7% of
      late deaths were valve-related. Pooled thromboembolism rate was 0.90%/year
      (95%CI:0.68-1.21), major bleeding 0.85%/year (95%CI:0.65-1.12), nonstructural
      valve dysfunction 0.39%/year (95%CI:0.21-0.76), endocarditis 0.41%/year
      (95%CI:0.29-0.57), valve thrombosis 0.14%/year (95%CI:0.08-0.25), structural
      valve deterioration 0.00%/year (zero events observed), and reintervention
      0.51%/year (95%CI:0.37-0.71), mostly due to nonstructural valve dysfunction and
      endocarditis. For a 45-year-old, for example, this translated to an estimated
      life expectancy of 19 years (general population: 34 years) and lifetime risks of
      thromboembolism, bleeding and reintervention of 18%, 15%, and 10%, respectively.
      Conclusion: This study demonstrates that outcome after mechanical AVR in non
      elderly adults is characterized by suboptimal survival and considerable lifetime
      risk of anticoagulation-related complications, but also reoperation. Non-elderly
      adult patients who are facing prosthetic valve selection are entitled to
      conveyance of evidence-based estimates of the risks and benefits of both
      mechanical and biological valve options in a shared decision-making process.

PMID- 29045650
TI  - Association between race and receipt of counselling or medication for smoking
      cessation in primary care.
AB  - Background: Previous evidence of race disparities in smoking cessation treatment
      has been limited to mostly survey studies which increase the potential for recall
      bias. We examined if African American versus white patients in primary care are
      less likely to receive any treatment or if race disparities are specific to the
      type of treatment offered using data pulled from a large electronic health record
      system. Methods: Medical record data from 3510 white and 2707 African American
      patients were available from primary care encounters between 2008 and 2015 and
      was used to define smoking status, cessation treatments (counselling and
      medication), and covariates. The association between race and type of smoking
      cessation treatment offered was measured by logistic regression models before and
      after adjusting for covariates. Results: Smoking cessation counselling was
      offered to 9.3% of African American and 7.8% of white patients, and a
      prescription for smoking cessation medication was offered to 12.3% of African
      American and 16.4% of white patients. After adjusting for covariates in logistic
      regression models, whites were significantly less likely than African American
      patients to receive smoking cessation counselling [odds ratio (OR) = 0.81; 95%
      confidence interval (CI) = 0.65-0.99] and were significantly more likely to
      receive a prescription for a smoking cessation medication (OR = 1.23; 95% CI =
      1.03-1.47). Conclusions: Less than 20% of smokers received any type of therapy to
      assist in smoking cessation. We observed a race disparity in type of smoking
      cessation therapy provided to white and African American primary care patients.
      Further research is needed to increase treatment rates and eliminate disparities.

PMID- 29045648
TI  - Staphylococcus aureus bloodstream infections in Latin America: results of a
      multinational prospective cohort study.
AB  - Background: Substantial heterogeneity in the epidemiology and management of
      Staphylococcus aureus bacteraemia (SAB) occurs in Latin America. We conducted a
      prospective cohort study in 24 hospitals from nine Latin American countries.
      Objectives: To assess the clinical impact of SAB in Latin America. Patients and
      methods: We evaluated differences in the 30 day attributable mortality among
      patients with SAB due to MRSA compared with MSSA involving 84 days of follow-up.
      Adjusted relative risks were calculated using a generalized linear model.
      Results: A total of 1030 patients were included. MRSA accounted for 44.7% of
      cases with a heterogeneous geographical distribution. MRSA infection was
      associated with higher 30 day attributable mortality [25% (78 of 312) versus
      13.2% (48 of 363), adjusted RR: 1.94, 95% CI: 1.38-2.73, P < 0.001] compared with
      MSSA in the multivariable analysis based on investigators' assessment, but not in
      a per-protocol analysis [13% (35 of 270) versus 8.1% (28 of 347), adjusted RR:
      1.10, 95% CI: 0.75-1.60, P = 0.616] or in a sensitivity analysis using 30 day all
      cause mortality [36% (132 of 367) versus 27.8% (123 of 442), adjusted RR: 1.09,
      95% CI: 0.96-1.23, P = 0.179]. MRSA infection was not associated with increased
      length of hospital stay. Only 49% of MSSA bloodstream infections (BSI) received
      treatment with beta-lactams, but appropriate definitive treatment was not
      associated with lower mortality (adjusted RR: 0.93, 95% CI: 0.70-1.23, P =
      0.602). Conclusions: MRSA-BSIs in Latin America are not associated with higher 30
      day mortality or longer length of stay compared with MSSA. Management of MSSA
      BSIs was not optimal, but appropriate definitive therapy did not appear to
      influence mortality.

PMID- 29045652
TI  - Influence of Pupation Substrate on Mass Production and Fitness of Adult
      Anastrepha obliqua Macquart (Diptera: Tephritidae) for Sterile Insect Technique
      Application.
AB  - Tephritid mass-rearing systems require an artificial substrate for pupation.
      Pupation substrate characteristics influence the quality of insects produced.
      Coconut fiber, as an alternative to the conventional pupation substrate
      vermiculite, was evaluated for Anastrepha obliqua Macquart (Diptera: Tephritidae)
      pupation behavior (pupation patterns, distribution, respiration rate, and pupal
      weight) and adult fitness (adult eclosion time, flight ability, and male mating
      competitiveness). Pupation percentage at 24 h, pupal weight, and flight ability
      were not significantly affected by substrate type. Adult eclosion levels of 50%
      were reached at 29.7 and 41.6 h for coconut fiber and vermiculite, respectively.
      Pupae distribution patterns differed between substrates because the larval
      aggregation level was reduced during the pupation process in coconut fiber. The
      pupae aggregation was three times greater in vermiculite than in coconut fiber. A
      higher respiratory rate in the last days of pupation and adult eclosion were
      recorded in the insects maintained in coconut fiber. Coconut fiber suitability as
      a pupation substrate for quality mass production of pupae and its implications
      for sterile insect technique are discussed.

PMID- 29045649
TI  - Understanding Evolutionary Impacts of Seasonality: An Introduction to the
      Symposium.
AB  - Seasonality is a critically important aspect of environmental variability, and
      strongly shapes all aspects of life for organisms living in highly seasonal
      environments. Seasonality has played a key role in generating biodiversity, and
      has driven the evolution of extreme physiological adaptations and behaviors such
      as migration and hibernation. Fluctuating selection pressures on survival and
      fecundity between summer and winter provide a complex selective landscape, which
      can be met by a combination of three outcomes of adaptive evolution: genetic
      polymorphism, phenotypic plasticity, and bet-hedging. Here, we have identified
      four important research questions with the goal of advancing our understanding of
      evolutionary impacts of seasonality. First, we ask how characteristics of
      environments and species will determine which adaptive response occurs. Relevant
      characteristics include costs and limits of plasticity, predictability, and
      reliability of cues, and grain of environmental variation relative to generation
      time. A second important question is how phenological shifts will amplify or
      ameliorate selection on physiological hardiness. Shifts in phenology can preserve
      the thermal niche despite shifts in climate, but may fail to completely conserve
      the niche or may even expose life stages to conditions that cause mortality.
      Considering distinct environmental sensitivities of life history stages will be
      key to refining models that forecast susceptibility to climate change. Third, we
      must identify critical physiological phenotypes that underlie seasonal adaptation
      and work toward understanding the genetic architectures of these responses. These
      architectures are key for predicting evolutionary responses. Pleiotropic genes
      that regulate multiple responses to changing seasons may facilitate coordination
      among functionally related traits, or conversely may constrain the expression of
      optimal phenotypes. Finally, we must advance our understanding of how changes in
      seasonal fluctuations are impacting ecological interaction networks. We should
      move beyond simple dyadic interactions, such as predator prey dynamics, and
      understand how these interactions scale up to affect ecological interaction
      networks. As global climate change alters many aspects of seasonal variability,
      including extreme events and changes in mean conditions, organisms must respond
      appropriately or go extinct. The outcome of adaptation to seasonality will
      determine responses to climate change.

PMID- 29045651
TI  - Clinical decision support alert malfunctions: analysis and empirically derived
      taxonomy.
AB  - Objective: To develop an empirically derived taxonomy of clinical decision
      support (CDS) alert malfunctions. Materials and Methods: We identified CDS alert
      malfunctions using a mix of qualitative and quantitative methods: (1) site visits
      with interviews of chief medical informatics officers, CDS developers, clinical
      leaders, and CDS end users; (2) surveys of chief medical informatics officers;
      (3) analysis of CDS firing rates; and (4) analysis of CDS overrides. We used a
      multi-round, manual, iterative card sort to develop a multi-axial, empirically
      derived taxonomy of CDS malfunctions. Results: We analyzed 68 CDS alert
      malfunction cases from 14 sites across the United States with diverse electronic
      health record systems. Four primary axes emerged: the cause of the malfunction,
      its mode of discovery, when it began, and how it affected rule firing. Build
      errors, conceptualization errors, and the introduction of new concepts or terms
      were the most frequent causes. User reports were the predominant mode of
      discovery. Many malfunctions within our database caused rules to fire for
      patients for whom they should not have (false positives), but the reverse (false
      negatives) was also common. Discussion: Across organizations and electronic
      health record systems, similar malfunction patterns recurred. Challenges included
      updates to code sets and values, software issues at the time of system upgrades,
      difficulties with migration of CDS content between computing environments, and
      the challenge of correctly conceptualizing and building CDS. Conclusion: CDS
      alert malfunctions are frequent. The empirically derived taxonomy formalizes the
      common recurring issues that cause these malfunctions, helping CDS developers
      anticipate and prevent CDS malfunctions before they occur or detect and resolve
      them expediently.

PMID- 29045653
TI  - A quality improvement project to reduce hypothermia in preterm infants on
      admission to the neonatal intensive care unit.
AB  - Objective: To study effectiveness of quality improvement interventions in
      reducing hypothermia in preterm infants on admission to neonatal intensive care
      unit. Design: Quality improvement methodologies including multidisciplinary
      planning and implementation of evidence-based interventions. Data during and post
      implementation were collected. Setting and participants: In total, 84 preterm
      infants with birth weights <= 1500 g delivered during implementation period
      (October 2008-April 2009) were compared with 168 historical controls and 947
      infants in the subsequent 4 years. Intervention(s): In addition to routine
      interventions, delivery room temperatures were increased, and use of full-body
      polyethylene wraps and woollen caps were implemented during initial
      stabilization. Education and training were provided to reinforce the new
      interventions. Main Outcome Measure(s): Primary outcome was incidence of
      hypothermia and mean admission temperature. Secondary outcomes were rates of
      intraventricular haemorrhage and mortality. Results: Incidence of admission
      hypothermia decreased from 79.4 to 40.5% (P < 0.001), constituting a 49%
      improvement (OR = 0.177, 95% CI: 0.099-0.316). Mean admission temperature
      increased from 35.8 +/- 0.8 degrees C to 36.5 +/- 0.7 degrees C (P < 0.001).
      Hyperthermia incidence was higher at 6% compared to baseline of 1.3% (P = 0.049).
      The incidence of admission hypothermia remained stable at 47.4% in the 4 years
      post-implementation. Rates of intraventricular haemorrhage and mortality remained
      unchanged. Small for gestation, low 5-min Apgar score and singleton delivery were
      factors found to be associated with admission hypothermia. Conclusion: The
      implementation of evidence-based best practices resulted in significant reduction
      in admission hypothermia in preterm infants, which persisted for 4 years post
      implementation. The practices have since become standard of care in our
      institution.

PMID- 29045654
TI  - Crop Seedling Susceptibility to Armadillidium vulgare (Isopoda: Armadillidiidae)
      and Ommatoiulus moreletii (Diplopoda: Iulidae).
AB  - The isopod, Armadillidium vulgare (Latreille) (Isopoda: Armadillidiidae), and the
      millipede, Ommatoiulus moreletii (Lucas) (Diplopoda: Iulidae), are increasingly
      being reported as pests of emerging broadacre crop seedlings in southern
      Australia. This is thought to be due to the increased adoption of stubble
      retention practices, leading to increased abundance of these soil-dwelling
      organisms. Here, we evaluate the propensity of A. vulgare and O. moreletii to
      damage a range of crop seedlings. Through the combined analysis of a controlled
      feeding trial and field reports, we show A. vulgare is able to feed on and damage
      a range of pulses, legumes, cereals, and oilseeds, as emerging seedlings. O.
      moreletii had a more restricted range of feeding, being limited to lupin,
      lucerne, and canola in the feeding trial. These results are discussed in the
      context of developing pest management guidelines for these species.

PMID- 29045656
TI  - Gougerot-Sjogren-like syndrome under PD-1 inhibitor treatment.

PMID- 29045657
TI  - Forecasting Spring Emergence of the Asian Corn Borer, Ostrinia furnacalis
      (Lepidoptera: Crambidae), Based on Postdiapause Development Rate.
AB  - This study was conducted to develop temperature-dependent postdiapause
      development models of overwintering larvae of the Asian corn borer, Ostrinia
      furnacalis Guenee (Lepidoptera: Crambidae), and to evaluate the models'
      forecasting accuracy using spring adult emergence data. Overwintering larvae were
      collected at three different times: 24 February (first), 23 March (second), and
      25 April (third), 2005. The developmental periods of each collection colony were
      measured at eight constant temperatures, and those developmental rates were
      modeled with linear and nonlinear regression. One linear and three nonlinear
      models provided good fits of developmental rate to temperature across all
      colonies (r2 = 0.96-0.99). The distribution of development completion time was
      modeled with a Weibull equation that fit data from the second (r2 = 0.92) and
      third (r2 = 0.97) colonies better than the first (r2 = 0.87). A Lactin 2 model
      based on data from the first colony was statistically the best model to describe
      the relationship between temperature and the postdiapause development rate of O.
      furnacalis (r2adj = 0.99). However, validation results based on the field data
      showed that the Logan 6 model combined with the Weibull model (based on the
      second colony) was well describing spring adult emergence patterns up to 50%
      cumulative emergence date.

PMID- 29045655
TI  - Determinants of the Efficacy of Natural Selection on Coding and Noncoding
      Variability in Two Passerine Species.
AB  - Population genetic theory predicts that selection should be more effective when
      the effective population size (Ne) is larger, and that the efficacy of selection
      should correlate positively with recombination rate. Here, we analyzed the
      genomes of ten great tits and ten zebra finches. Nucleotide diversity at 4-fold
      degenerate sites indicates that zebra finches have a 2.83-fold larger Ne. We
      obtained clear evidence that purifying selection is more effective in zebra
      finches. The proportion of substitutions at 0-fold degenerate sites fixed by
      positive selection (alpha) is high in both species (great tit 48%; zebra finch
      64%) and is significantly higher in zebra finches. When alpha was estimated on GC
      conservative changes (i.e., between A and T and between G and C), the estimates
      reduced in both species (great tit 22%; zebra finch 53%). A theoretical model
      presented herein suggests that failing to control for the effects of GC-biased
      gene conversion (gBGC) is potentially a contributor to the overestimation of
      alpha, and that this effect cannot be alleviated by first fitting a demographic
      model to neutral variants. We present the first estimates in birds for alpha in
      the untranslated regions, and found evidence for substantial adaptive changes.
      Finally, although purifying selection is stronger in high-recombination regions,
      we obtained mixed evidence for alpha increasing with recombination rate,
      especially after accounting for gBGC. These results highlight that it is
      important to consider the potential confounding effects of gBGC when quantifying
      selection and that our understanding of what determines the efficacy of selection
      is incomplete.

PMID- 29045658
TI  - Exendin-4, a Glucagonlike Peptide-1 Receptor Agonist, Attenuates Breast Cancer
      Growth by Inhibiting NF-kappaB Activation.
AB  - Incretin therapies have received much attention because of their tissue
      protective effects, which extend beyond those associated with glycemic control.
      Cancer is a primary cause of death in patients who have diabetes mellitus. We
      previously reported antiprostate cancer effects of the glucagonlike peptide-1
      (GLP-1) receptor (GLP-1R) agonist exendin-4 (Ex-4). Breast cancer is one of the
      most common cancers in female patients who have type 2 diabetes mellitus and
      obesity. Thus, we examined whether GLP-1 action could attenuate breast cancer.
      GLP-1R was expressed in human breast cancer tissue and MCF-7, MDA-MB-231, and KPL
      1 cell lines. We found that 0.1 to 10 nM Ex-4 significantly decreased the number
      of breast cancer cells in a dose-dependent manner. Although Ex-4 did not induce
      apoptosis, it attenuated breast cancer cell proliferation significantly and dose
      dependently. However, the dipeptidyl peptidase-4 inhibitor linagliptin did not
      affect breast cancer cell proliferation. When MCF-7 cells were transplanted into
      athymic mice, Ex-4 decreased MCF-7 tumor size in vivo. Ki67 immunohistochemistry
      revealed that breast cancer cell proliferation was significantly reduced in
      tumors extracted from Ex-4-treated mice. In MCF-7 cells, Ex-4 significantly
      inhibited nuclear factor kappaB (NF-kappaB ) nuclear translocation and target
      gene expression. Furthermore, Ex-4 decreased both Akt and IkappaB
      phosphorylation. These results suggest that GLP-1 could attenuate breast cancer
      cell proliferation via activation of GLP-1R and subsequent inhibition of NF
      kappaB activation.

PMID- 29045659
TI  - Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with
      untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20
      study results.
AB  - Background: Metastatic colorectal cancer frequently occurs in elderly patients.
      Bevacizumab in combination with front line chemotherapy (CT) is a standard
      treatment but some concern raised about tolerance of bevacizumab for these
      patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of
      bevacizumab according to specific end points in this population. Patients and
      methods: Patients aged 75 years and over were randomly assigned to bevacizumab +
      CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according
      to investigator's choice. The composite co-primary end point, assessed 4 months
      after randomization, was based on efficacy (tumor control and absence of decrease
      of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities
      and unexpected hospitalization). For each arm, the treatment will be consider as
      inefficient if 20% or less of the patients met the efficacy criteria and not safe
      if 40% or less met the safety criteria. Results: About 102 patients were
      randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end
      point was met for efficacy in 50% and 58% and for safety in 61% and 71% of
      patients in BEV and CT, respectively. Median progression-free survival was 9.7
      months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in
      BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and
      10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities
      (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe
      and efficient. Both arms met the primary safety and efficacy criteria.

PMID- 29045660
TI  - Evaluation of Off-season Potential Breeding Sources for Spotted Wing Drosophila
      (Drosophila suzukii Matsumura) in Michigan.
AB  - It has been suggested that fruit wastes including dropped and unharvested fruits,
      and fruit byproducts (i.e., pomace) found in fruit plantings and cideries or wine
      making facilities could serve as potential off-season breeding sites for spotted
      wing Drosophila (Drosophila suzukii Matsumura (Diptera: Drosophilidae)). This
      idea, however, has yet to be widely tested. The goal of our study was to
      determine the potential of dropped fruit and fruit wastes as Fall spotted wing
      Drosophila breeding resources in Michigan, USA. Fruit waste samples were
      collected from 15 farms across the lower peninsula of Michigan and were evaluated
      for spotted wing Drosophila and other drosophilid emergence and used in host
      suitability bioassays. All of the dropped apples, pears, grapes, and raspberries
      and 40% of apple and 100% of grape fruit pomace evaluated were found to contain
      spotted wing Drosophila with the highest numbers collected from dropped grapes
      and pears. Greater spotted wing Drosophila recovery was found in fruit wastes at
      sites attached with cideries and wine-making facilities and with multiple
      cultivated fruit crops than sites with no cideries and only one crop. Females
      oviposited in raspberry, pear, apple, grape, apple pomace and grape pomace
      samples with the highest rates of reproduction in raspberries. Our results
      demonstrate that fruit wastes including dropped berry, pomme and stone fruits, as
      well as fruit compost may be important late season reproductive resources for
      spotted wing Drosophila.

PMID- 29045661
TI  - Factors associated with malnutrition among children <5 years old in Burkina Faso:
      evidence from the Demographic and Health Surveys IV 2010.
AB  - Objective: To assess the factors associated with malnutrition among children <5
      years in Burkina Faso. Design: This study was based on secondary analysis of
      cross-sectional population-based data from Burkina-Faso Demographic Health
      Surveys 2010. Setting: This study was carried out in Burkina Faso, West Africa.
      Participants: The participants were 6337 children <5 years and their mothers.
      Main outcome measures: Demographic characteristics, child nutrition and health
      status, and maternal and household information were collected. Survey-specific
      SAS procedures for weighting, clustering and stratification in the survey design
      were used. The distribution of different nutritional status, such as underweight,
      stunting and wasting and the effects of risk factors on malnutrition was
      analyzed. Results: Out of 6337 children <5 years, 51.0% of children were male and
      57.8% of children had an average size at birth. There were 15.6, 21.5 and 10.6%
      of children who recently suffered from diarrhea, fever and acute respiratory
      infection, respectively. Child sex, age, size at birth, child morbidity, mother's
      education and body mass index and household wealth index were significantly
      associated with undernutrition among children <5 years in Burkina Faso.
      Conclusions: In addition to the improvement of household wealth index, more
      health and nutritional education for mothers should be implemented by the
      government to improve health and nutritional status of children <5 years in
      Burkina Faso.

PMID- 29045662
TI  - Resistance Monitoring of Four Insecticides and a Description of an Artificial
      Diet Incorporation Method for Chilo suppressalis (Lepidoptera: Crambidae).
AB  - Chilo suppressalis (Walker; Lepidoptera: Crambidae) is one of the most damaging
      rice pests in China. Insecticides play a major role in its management. We
      describe how we monitored the resistance of C. suppressalis to four insecticides
      in seven field populations from Jiangxi, Hubei, and Hunan Provinces, China, in
      2014-2016. The topical application method for resistance monitoring was suitable
      for triazophos, monosultap, and abamectin. The conventional rice seedling dipping
      method proved ineffective for testing chlorantraniliprole so the new artificial
      diet incorporation method was substituted. This new method provided more
      consistent results than the other methods, once baseline toxicity data had been
      established. All populations had moderate to high resistance to triazophos from
      2014 to 2016. Monosultap resistance in two populations increased from low in 2014
      to moderate in 2016 and the other five populations showed moderate to high-level
      resistance throughout. Abamectin resistance in three populations increased from
      sensitive or low in 2014 to moderate in 2015-2016, and the other populations had
      moderate to high levels of resistance. Resistance to chlorantraniliprole
      increased from sensitive or low in 2014 to moderate to high in 2016. These
      results suggested that resistance management strategies should be developed
      according to the needs of a specific location. It was suggested that, in these
      localities, organophosphate insecticides should be prohibited, the application of
      nereistoxin, macrolide antibiotic, and diamide insecticides should be limited,
      and other insecticides, including spinetoram and methoxyfenozide, that exhibited
      no resistance should be used rationally and in rotation to delay resistance
      development.

PMID- 29045663
TI  - Effect of Planting Depth and Irrigation Regimes on Potato Tuberworm (Lepidoptera:
      Gelechiidae) Damage Under Central Pivot Irrigation in the Lower Columbia Basin.
AB  - Phthorimaea operculella Zeller has proven to be a limitation to potato
      production. Although pesticides can effectively reduce P. operculella
      populations, information regarding effective cultural controls is lacking. The
      following study was designed to evaluate the effect of different irrigation
      regimes and planting depths to reduce P. operculella damage under central pivot
      irrigation. Field trials were conducted in 2007 and 2008 and experimental plots
      followed standard growers' agronomic practices. Three levels of irrigation were
      used: optimal, 10% less than optimal, and 10% above optimal; potato planting
      depth was arranged as shallow, normal, and deep; normal planting was considered
      tubers planted at 0.15 m depth. Mines and number of larvae per plant were counted
      weekly until harvest and tuber damage, above and below ground, was estimated.
      Overall, irrigation had a stronger effect than planting depth but there were not
      a clear planting depth:irrigation interaction. Both years, sampling dates had a
      strong effect on the number of mines per plant where the number of mines per
      plant increased as season progressed. There were not clear trends related to
      mines per plant, mines per tuber or yield related to planting depth, but there
      were strong tendencies related to irrigation. The data presented herein provide
      valuable information regarding the potential to adjust irrigation to warrant
      better P. operculella control.

PMID- 29045664
TI  - Understanding the impact of accreditation on quality in healthcare: A grounded
      theory approach.
AB  - Objective: To explore how organizations respond to and interact with the
      accreditation process and the actual and potential mechanisms through which
      accreditation may influence quality. Design: Qualitative grounded theory study.
      Setting: Organizations who had participated in Accreditation Canada's Qmentum
      program during January 2014-June 2016. Participants: Individuals who had
      coordinated the accreditation process or were involved in managing or promoting
      quality. Results: The accreditation process is largely viewed as a quality
      assurance process, which often feeds in to quality improvement activities if the
      feedback aligns with organizational priorities. Three key stages are required for
      accreditation to impact quality: coherence, organizational buy-in and
      organizational action. These stages map to constructs outlined in Normalization
      Process Theory. Coherence is established when an organization and its staff
      perceive that accreditation aligns with the organization's beliefs, context and
      model of service delivery. Organizational buy-in is established when there is
      both a conceptual champion and an operational champion, and is influenced by both
      internal and external contextual factors. Quality improvement action occurs when
      organizations take purposeful action in response to observations, feedback or
      self-reflection resulting from the accreditation process. Conclusions: The
      accreditation process has the potential to influence quality through a series of
      three mechanisms: coherence, organizational buy-in and collective quality
      improvement action. Internal and external contextual factors, including
      individual characteristics, influence an organization's experience of
      accreditation.

PMID- 29045665
TI  - DNA Barcode Reference Library for the African Citrus Triozid, Trioza erytreae
      (Hemiptera: Triozidae): Vector of African Citrus Greening.
AB  - Citrus (Citrus spp.) production continues to decline in East Africa, particularly
      in Kenya and Tanzania, the two major producers in the region. This decline is
      attributed to pests and diseases including infestation by the African citrus
      triozid, Trioza erytreae (Del Guercio) (Hemiptera: Triozidae). Besides direct
      feeding damage by adults and immature stages, T. erytreae is the main vector of
      'Candidatus Liberibacter africanus', the causative agent of Greening disease in
      Africa, closely related to Huanglongbing. This study aimed to generate a novel
      barcode reference library for T. erytreae in order to use DNA barcoding as a
      rapid tool for accurate identification of the pest to aid phytosanitary measures.
      Triozid samples were collected from citrus orchards in Kenya, Tanzania, and South
      Africa and from alternative host plants. Sequences generated from populations in
      the study showed very low variability within acceptable ranges of species. All
      samples analyzed were linked to T. erytreae of GenBank accession number KU517195.
      Phylogeny of samples in this study and other Trioza reference species was
      inferred using the Maximum Likelihood method. The phylogenetic tree was
      paraphyletic with two distinct branches. The first branch had two clusters: 1)
      cluster of all populations analyzed with GenBank accession of T. erytreae and 2)
      cluster of all the other GenBank accession of Trioza species analyzed except T.
      incrustata Percy, 2016 (KT588307.1), T. eugeniae Froggatt (KY294637.1), and T.
      grallata Percy, 2016 (KT588308.1) that occupied the second branch as outgroups
      forming sister clade relationships. These results were further substantiated with
      genetic distance values and principal component analyses.

PMID- 29045666
TI  - Quality Improvement Feature Series Article 4: Advanced Designs for Quality
      Improvement Studies.
AB  - Each quality improvement (QI) project has an implicit study design, although
      these designs are not discussed as commonly as they are in clinical research.
      Most QI projects fall under the quasi-experimental study category, in which
      observations are made before and after the implementation of an intervention(s).
      The simplest and most commonly used for QI studies is the pre-post design, in
      which observations are made before and after each intervention that was
      implemented over a specified period. More sophisticated designs for QI studies
      enable a study team to draw stronger inferences about the system that is being
      changed and the individual effects of the interventions that are implemented. In
      the final commentary in this QI series, we discuss these study designs and focus
      on the strengths and weaknesses of more sophisticated designs, including cluster
      randomized, stepped-wedge, and factorial designs.

PMID- 29045667
TI  - Survey of Reproductive Experiences and Outcomes of Cancer Survivors Who Stored
      Reproductive Material Before Treatment.
AB  - STUDY QUESTION: What are the reproductive experiences and outcomes of people who
      store reproductive material before cancer treatment? SUMMARY ANSWER: Of
      respondents who had tried to achieve pregnancy since completing cancer treatment
      almost all had succeeded, in most cases through natural conception. WHAT IS KNOWN
      ALREADY: People of reproductive age who are diagnosed with cancer can
      cryopreserve reproductive material to guard against the adverse effects on
      fertility of gonadotoxic treatment. Little is known about the reproductive
      outcomes of people who undergo fertility preservation before cancer treatment.
      STUDY DESIGN, SIZE, DURATION: Cross-sectional survey. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Women and men who had stored reproductive material before
      cancer treatment at two private and one public fertility clinics up to June 2014
      and were at least 18 years old at the time were identified from medical records
      and invited to complete an anonymous questionnaire about their reproductive
      experiences. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 870 potential
      respondents 302 (171 female and 131 male) returned completed questionnaires
      yielding a response rate of 34.5% (39.5% and 29.7% for female and male
      respondents, respectively). Current age was similar for women and men (37.2
      years) but men had been diagnosed with cancer significantly earlier in life than
      women (28.2 versus 30.3 years, P = 0.03). Almost two-thirds of respondents wished
      to have a child or another child in the future, some of whom knew that they were
      unable to. One in ten respondents was a parent before the cancer diagnosis and
      around one-third had had a child since diagnosis or was pregnant (or a partner in
      pregnancy) at the time of the survey. Of those who had tried to conceive since
      completing cancer treatment (N = 119) 84% (79% of women and 90% of men) had had a
      child or were pregnant (or a partner in pregnancy). Most of the pregnancies since
      the diagnosis of cancer occurred after natural conception (58/100, 58%). Of the
      22 women (13% of all women) and 35 men (27% of all men) who had used their stored
      reproductive material four women (18%) and 28 men (80%) had had a child or were
      pregnant or a partner in pregnancy at the time of completing the survey. The most
      commonly stated reason for not using the stored material was not being ready to
      try for a baby. LIMITATIONS, REASON FOR CAUTION: The relatively low response
      rate, particularly among men, means that participation bias may have influenced
      the findings. As type of cancer was self-reported and we did not ask questions
      about respondents' cancer treatments, it is not possible to link reproductive
      outcomes to type of cancer or cancer treatment. Also, there is no way of
      comparing the sample with the populations they were drawn from as data on
      reproductive outcomes of people who store reproductive material before cancer
      treatment are not collected routinely. This might have led to over- or
      underestimates of the reproductive experiences and outcomes reported in this
      paper. WIDER IMPLICATIONS OF THE FINDINGS: The findings add to the limited
      evidence about the reproductive outcomes of this growing group of people and can
      be used to inform the advice given to those contemplating fertility preservation
      in the context of cancer. STUDY FUNDING/COMPETING INTERESTS: The study was funded
      by the National Health and Medical Research Council (APP1042347). The authors
      have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not
      applicable.

PMID- 29045668
TI  - Sublethal Effects of vATPase-A and Snf7 dsRNAs on Biology of Southern Corn
      Rootworm, Diabrotica undecimpunctata howardi Barber.
AB  - RNA interference is a powerful tool against corn rootworm. Adults and neonates of
      southern corn rootworm, Diabrotica undecimpunctata howardi Barber (Coleoptera:
      Chrysomelidae), were exposed to the LC50 of vATPase-A and Snf7 double-stranded
      RNAs (dsRNAs), and the effects on female fecundity, egg viability, male fitness
      as measured by sperm viability and mating capacity, larval recovery along with
      dry weight, and instar determination 10 d after exposure to dsRNA, were
      determined. Significant reductions were observed for a number of parameters in
      dsRNA-exposed rootworms relative to control treatments. Female fecundity and
      larval recovery were significantly reduced after exposure to both dsRNAs. In
      addition, larval dry weight and recovery of 2nd and 3rd instars along with dry
      weight for 3rd instars were significantly reduced after neonate exposure to
      vATPase-A dsRNA. Neither dsRNA affected male capacity to mate or sperm viability
      after exposure to the respective LC50s. After 10 d of feeding on untreated corn
      roots, neonates that survived exposure for 2 d to the vATPase-A dsRNA LC50
      exhibited lower dry weight than the control. There was significant gene knockdown
      in adult males and females after exposure for 5 d to LC50 of vATPase-A and Snf7
      dsRNAs. The parameters are discussed in terms of fitness and possible outcomes
      after deployment of corn hybrids expressing dsRNAs.

PMID- 29045669
TI  - Genetic Decoupling of Thermal Hardiness across Metamorphosis in Drosophila
      melanogaster.
AB  - As organisms age the environment fluctuates, exerting differential selection
      across ontogeny. In particular, highly seasonal environments expose life stages
      to often drastically different thermal environments. This developmental variation
      is particularly striking in organisms with complex life cycles, wherein life
      history stages also exhibit distinct morphologies, physiologies, and behaviors.
      Genes acting pleiotropically on thermal responses may produce genetic
      correlations across ontogeny, constraining the independent evolution of each life
      stage to their respective thermal environments. To investigate whether
      developmental genetic correlations constrain the evolution thermal hardiness of
      the fly Drosophila melanogaster, we applied quantitative genetic analyses to cold
      hardiness measured in both larvae and adults from isogenic lines of the
      Drosophila Genetic Reference Panel (DGRP), using survival at stressful low
      temperatures as the phenotypic metric. Using full genome resequencing data for
      the DGRP, we also implemented genome-wide association (GWA) analysis using
      Bayesian Sparse Linear Mixed Models (BSLMMs) to estimate associations between
      naturally segregating variation and cold hardiness for both larvae and adults.
      Quantitative genetic analyses revealed no significant genetic correlation for
      cold hardiness between life stages, suggesting complete genetic decoupling of
      thermal hardiness across the metamorphic boundary. Both quantitative genetic and
      GWA analyses suggested that polygenic variation underlies cold hardiness in both
      stages, and that associated loci largely affected one stage or the other, but not
      both. However, reciprocal enrichment tests and correlations between BSLMM
      parameters for each life stage support some shared physiological mechanisms that
      may reflect common cellular thermal response pathways. Overall, these results
      suggest no developmental genetic constraints on cold hardiness across
      metamorphosis in D. melanogaster, an important consideration in evolutionary
      models of responses to changing climates. Genetic correlations for environmental
      sensitivity across ontogeny remains largely unexplored in other organisms, thus
      assessing the generality of genetic decoupling will require further quantitative
      or population genetic analysis in additional species.

PMID- 29045670
TI  - Impact of Age-Related Mitochondrial Dysfunction and Exercise on Intestinal
      Microbiota Composition.
AB  - Mitochondrial dysfunction is prevalent in the aging gastrointestinal tract. We
      investigated whether mitochondrial function in aging colonic crypts and exercise
      influences microbial gut communities in mice. Twelve PolgAmut/mut mice were
      randomly divided into a sedentary and exercise group at 4 months. Seven-aged
      matched PolgA+/+ mice remained sedentary throughout. Stool samples were collected
      at 4, 7, and 11 months, and bacterial profiling was achieved through 16S rRNA
      sequencing profiling. Mitochondrial enzyme activity was assessed in colonic
      epithelial crypts at 11 months for PolgAmut/mut and PolgA+/+ mice. Sedentary and
      exercised PolgAmut/mut mice had significantly higher levels of mitochondrial
      dysfunction than PolgA+/+ mice (78%, 77%, and 1% of crypts, respectively).
      Bacterial profiles of sedentary PolgAmut/mut mice were significantly different
      from the sedentary PolgA+/+ mice, with increases in Lactobacillus and Mycoplasma,
      and decreases in Alistipes, Odoribacter, Anaeroplasma, Rikenella,
      Parabacteroides, and Allobaculum in the PolgAmut/mut mice. Exercise did not have
      any impact upon gut mitochondrial dysfunction; however, exercise did increase gut
      microbiota diversity and significantly increased bacterial genera Mucispirillum
      and Desulfovibrio. Mitochondrial dysfunction is associated with changes in the
      gut microbiota. Endurance exercise moderated some of these changes, establishing
      that environmental factors can influence gut microbiota, despite mitochondrial
      dysfunction.

PMID- 29045671
TI  - Association between self-rated health and ideal cardiovascular health: The
      Baptist Health South Florida Employee Study.
AB  - Background: There is increasing evidence of the role psychosocial factors play as
      determinants of cardiovascular health (CVH). We examined the association between
      self-rated health (SRH) and ideal CVH among employees of a large healthcare
      organization. Methods: Data were collected in 2014 from employees of Baptist
      Health South Florida during an annual voluntary health risk assessment and
      wellness fair. SRH was measured using a self-administered questionnaire where
      responses ranged from poor, fair, good, very good to excellent. A CVH score (the
      proxy for CVH) that ranged from 0 to 14 was calculated, where 0-8 indicate an
      inadequate score, 9-10, average and 11-14, optimal. A multinomial logistic
      regression was used to examine the association between SRH and CVH. Results: Of
      the 9056 participants, 75% were female and mean age (SD) was 43 +/- 12 years. The
      odds of having a higher CVH score increased as SRH improved. With participants
      who reported their health status as poor-fair serving as reference, adjusted odds
      ratios for having an optimal CVH score by the categories of SRH were: excellent,
      21.04 (15.08-29.36); very good 10.04 (7.25-13.9); and good 3.63 (2.61-5.05).
      Conclusion: Favorable SRH was consistently associated with better CVH.

PMID- 29045672
TI  - Dynamics of evidence-informed health policy making in Pakistan.
AB  - Incorporating evidence is fundamental to maintaining the general acceptance and
      efficiency in public policies. In Pakistan, different actors-local and global
      strive to facilitate the development of evidence-informed health policies.
      Effective involvement however, requires knowledge of the country-context, i.e.
      knowing the intricacies of how policies are formulated in Pakistan. Obtaining
      this knowledge is one of the key steps to making interventions impactful. We
      carried out a qualitative study to explore the environment of evidence-informed
      health policy in Pakistan. The study involved 89 participants and comprised three
      phases including: (1) literature review followed by a consultative meeting with
      key informants to explore the broad contours of policy formulation, (2) in-depth
      interviews with participants belonging to various levels of health system to
      discuss these contours and (3) a roundtable with experts to share and solidify
      the findings. Policy development is a slow, non-linear process with variable room
      for incorporation of evidence. Political actors dominate decisions that impact
      all aspects of policy, i.e. context, process and content. Research contributions
      are mostly influenced by the priorities of donor agencies-the usual proponents
      and sponsors of the generation of evidence. Since the devolution of health system
      in 2012, Pakistan's provinces continue to follow the same processes as before
      2012, with little capacity to generate evidence and incorporate it into health
      policy. This study highlights the non-systematic, nearly ad hoc way of developing
      health policy in the country, overly dominated by political actors. Health
      advocates need to understand the policy process and the actors involved if they
      are to identify points of impact where their interaction with policy brings the
      maximum leverage. Moreover, an environment is needed where generation of data
      gains the importance it deserves and where capacities are enhanced for
      communicating and understanding evidence, as well as its incorporation into
      policy.

PMID- 29045674
TI  - RE: Proportion of Never-Smoker Non-Small Cell Lung Cancer Patients at Three
      Diverse Institutions.

PMID- 29045673
TI  - Age-related changes in the mitochondria of human mural granulosa cells.
AB  - STUDY QUESTION: What changes in the mitochondria of human mural granulosa cells
      (mGCs) with maternal aging? SUMMARY ANSWER: The mitochondrial membrane potential
      (MMP) and the ability of oxidative phosphorylation (OXPHOS) of mGCs declines with
      reproductive aging, accompanied with more abnormal mitochondria. WHAT IS KNOWN
      ALREADY: Mitochondria play an important role in the dialogue between the mGCs and
      oocytes. However, the underlying mechanism of mitochondrial dysfunction in mGCs
      in aging is still poorly understood. STUDY DESIGN SIZE, DURATION: In total, 149
      infertile women underwent IVF in the ART Centre of the Chinese PLA General
      Hospital, China from September 2016 to May 2017. Two age groups were
      investigated: the young group (<38 years old) and the old group (>=38 years old).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: The mitochondrial ultrastructure of
      mGCs was observed by transmission electron microscopy, and real-time quantitative
      polymerase chain reaction was applied to quantify the mitochondrial DNA (mtDNA)
      copy number, 4977-bp deleted DNA and mRNA expression of mitochondrial ATP
      synthases ATP5A1 and ATP5I. MMP was detected by flow cytometry and fluorescence
      microscopy, respectively. Reactive oxygen species (ROS) was tested by flow
      cytometry. A luminometer was used to measure the ATP levels and western blot to
      analyse the OXPHOS complex. MAIN RESULTS AND THE ROLE OF CHANCE: In the young
      group, mitochondria were mostly round or oval, with a few intact parallel tubular
      vesicular cristae and homogenous matrix density, while elongated mitochondria
      were mainly observed in the old group, which had numerous cristae and more high
      density matrix particles. Abnormal mitochondria were more common in aging women
      (P = 0.012). mtDNA relative copy number was positively correlated with maternal
      age (r = 0.294, P = 0.009) and we found no one with 4977-bp deleted mitochondria.
      JC-1 (dye used as an indicator of MMP) ratio in the old group was significantly
      lower than the young group (3.01 +/- 0.21 vs 3.85 +/- 0.27, P = 0.033).
      Intracellular ROS levels between the groups did not differ significantly (P =
      0.191). The intracellular ATP level in the young group was 1.75-fold higher than
      that of the advanced-age group (7.17 +/- 1.16 vs 4.15 +/- 0.60, P = 0.025). The
      protein expression of ATP5A1, as one of five proteins of OXPHOS, decreased with
      aging (P < 0.001). ATP5A1 mRNA expression was negatively correlated with aging (r
      = -0.341, P = 0.012). LIMITATIONS REASONS FOR CAUTION: The quantity of mGCs from
      some individual patient, especially an advanced-age individual, was small, which
      cannot meet the demands of all the detections. WIDER IMPLICATIONS OF THE
      FINDINGS: mGCs dysfunction with aging is mainly linked to impaired mitochondrial
      function, especially OXPHOS function. Improving the OXPHOS ability in mGCs should
      be the focus in resolving infertility among advanced age women and making mGCs
      the proper mitochondria donor cells in the autologous mitochondria
      transplantation to oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was
      supported by the grants of the National High Technology Research and Development
      Program of China, 863 Program No. SS2015AA020402, and the Key Projects of
      Military Medical Research, No. BWS11J058. There were no competing interests.

PMID- 29045675
TI  - Increased steroidogenesis promotes early-onset and severe vision loss in females
      with OPA1 dominant optic atrophy.

PMID- 29045676
TI  - Reproductive Plasticity of an Invasive Insect Pest, Rice Water Weevil
      (Coleoptera: Curculionidae).
AB  - Reproductive plasticity is a key determinant of species invasiveness. However,
      there are a limited number of studies addressing this issue in exotic insects.
      The rice water weevil Lissorhoptrus oryzophilus Kuschel (Coleoptera:
      Curculionidae), which is native to North America, is one of the most invasive
      insect pests in east Asia. In this study, we investigated the reproductive status
      of first-generation females (progeny of overwintered weevils) from five
      geographic regions in southern and northern China in the field, and reproductive
      status and ovipositional features of females provided with suitable host plants
      in the laboratory after collection. Under field conditions, a proportion of
      females oviposited, while the rest remained in diapause from all three southern
      regions investigated, but reproductive development did not take place in females
      from the two northern regions, where the weevil produces only one generation per
      year. However, when fed host plants in the laboratory, females from all regions
      laid eggs. They typically had a very short ovipositional period (3-6 d on average
      on rice at a temperature of 27 degrees C), laid a low number of eggs, and did not
      die soon after oviposition; this was different from common reproductive females.
      We concluded that first-generation L. oryzophilus females, which largely enter
      diapause after emergence, are highly plastic in their reproductive performance
      and are ready to reproduce under favorable conditions. Our results indicate the
      significance of their reproductive plasticity for geographic spread and
      population development.

PMID- 29045677
TI  - Response.

PMID- 29045679
TI  - Prostate Cancer Patient Characteristics Associated With a Strong Preference to
      Preserve Sexual Function and Receipt of Active Surveillance.
AB  - Background: Men with early-stage prostate cancer have multiple options that have
      similar oncologic efficacy but vary in terms of their impact on quality of life.
      In low-risk cancer, active surveillance is the option that best preserves
      patients' sexual function, but it is unknown if patient preference affects
      treatment selection. Our objectives were to identify patient characteristics
      associated with a strong preference to preserve sexual function and to determine
      whether patient preference and baseline sexual function level are associated with
      receipt of active surveillance in low-risk cancer. Methods: In this population
      based cohort of men with localized prostate cancer, baseline patient-reported
      sexual function was assessed using a validated instrument. Patients were also
      asked whether preservation of sexual function was very, somewhat, or not
      important. Prostate cancer disease characteristics and treatments received were
      abstracted from medical records. A modified Poisson regression model with robust
      standard errors was used to compute adjusted risk ratio (aRR) estimates. All
      statistical tests were two-sided. Results: Among 1194 men, 52.6% indicated a
      strong preference for preserving sexual function. Older men were less likely to
      have a strong preference (aRR = 0.98 per year, 95% confidence interval [CI] =
      0.97 to 0.99), while men with normal sexual function were more likely (vs poor
      function, aRR = 1.59, 95% CI = 1.39 to 1.82). Among 568 men with low-risk cancer,
      there was no clear association between baseline sexual function or strong
      preference to preserve function with receipt of active surveillance. However,
      strong preference may differnetially impact those with intermediate baseline
      function vs poor function (Pinteraction = .02). Conclusions: Treatment choice may
      not always align with patients' preferences. These findings demonstrate
      opportunities to improve delivery of patient-centered care in early prostate
      cancer.

PMID- 29045678
TI  - Enterococcus faecalis Modulates Immune Activation and Slows Healing During Wound
      Infection.
AB  - Enterococcus faecalis is one of the most frequently isolated bacterial species in
      wounds yet little is known about its pathogenic mechanisms in this setting. Here,
      we used a mouse wound excisional model to characterize the infection dynamics of
      E faecalis and show that infected wounds result in 2 different states depending
      on the initial inoculum. Low-dose inocula were associated with short-term, low
      titer colonization whereas high-dose inocula were associated with acute bacterial
      replication and long-term persistence. High-dose infection and persistence were
      also associated with immune cell infiltration, despite suppression of some
      inflammatory cytokines and delayed wound healing. During high-dose infection, the
      multiple peptide resistance factor, which is involved in resisting immune
      clearance, contributes to E faecalis fitness. These results comprehensively
      describe a mouse model for investigating E faecalis wound infection determinants,
      and suggest that both immune modulation and resistance contribute to persistent,
      nonhealing wounds.

PMID- 29045680
TI  - Report of a Novel Case of Anaplastic Olfactory Groove Meningioma and Its
      Methylation Subtype.
AB  - We report a novel case of a World Health Organization grade 3 anaplastic
      meningioma arising from the olfactory groove in an 83-year-old woman. Molecular
      and methylation profiling confirm this lesion to be an NF2 subtype, methylation
      class intermediate type B meningioma. As most meningiomas in this location are
      indolent SMO subtype lesions, our report suggests that even though rare,
      aggressive NF2 subtype meningiomas can also occur along the midline anterior
      skull base.

PMID- 29045681
TI  - International Patterns and Trends in Endometrial Cancer Incidence, 1978-2013.
AB  - Background: Cancers of the corpus uteri-primarily of the endometrium-rank as the
      sixth most common neoplasm in women worldwide. Analyses of the global patterns
      and trends of uterine cancer rates are needed in view of the ongoing obesity
      epidemic, a major risk factor for the disease. Methods: Data on endometrial
      cancer (ICD-10 C54) incidence from population-based cancer registries in 43
      populations, published in CI5plus or by registries, were extracted for 1978 to
      2013. Age-standardized incidence rates were computed for all ages and for pre-
      (25-49 years) and postmenopausal ages (50 years and older). Temporal trends were
      assessed with Joinpoint analysis, and the effects of birth cohort and year of
      diagnosis on the overall trends were examined using age-period-cohort modeling.
      Results: In 2006 to 2007, rates varied 10-fold across countries. The highest
      rates were in North America, Eastern and Northern Europe (19 cases per 100 000
      among whites in the United States, 95% confidence interval [CI] = 18 to 20, and
      in Slovakia, 95% CI = 18 to 21), and the lowest rates were in middle-income
      countries (South Africa 1, 95% CI = 0 to 3, and India 3, 95% CI = 3 to 4). Rates
      during the most recent 10 data years increased in 26 of the 43 populations
      considered in this study, with South Africa and several countries in Asia showing
      the largest increase. The risk of endometrial cancer increased both in
      consecutive generations and over time in 11 of 23 populations, with the increases
      more pronounced in Japan, the Philippines, Belarus, Singapore, Costa Rica, and
      New Zealand. Conclusions: Endometrial cancer incidence rates increased over time
      and in successive generations in several countries, especially in those countries
      with rapid socioeconomic transitions.

PMID- 29045682
TI  - Effects of Hermetic Storage on Adult Sitophilus oryzae L. (Coleoptera:
      Curculionidae) Acoustic Activity Patterns and Mortality.
AB  - Hermetic storage is of interest to farmers and warehouse managers as a method to
      control insect pests in small storage facilities. To develop improved
      understanding of effects of hermetic storage on insect pest activity and
      mortality over time, oxygen levels, acoustic signals, and observations of visual
      movement were recorded from replicates of 25, 50, and 100 adult Sitophilus oryzae
      (L.) (Coleoptera: Curculionidae) hermetically sealed in 500- and 1,000-ml glass
      jars. Recordings were done for 28 d; twice daily for the first 6 d and twice
      weekly thereafter. Insect sounds were analyzed as short bursts (trains) of
      impulses with spectra that matched average spectra (profiles) of previously
      verified insect sound impulses. Oxygen consumption was highest in treatments of
      100 insects/500-ml jar and lowest in 25/1000-ml jars. The rates of bursts per
      insect, number of impulses per burst, and rates of burst impulses per insect
      decreased as the residual oxygen levels decreased in each treatment. Activity
      rates <0.02 bursts s-1, the acoustic detection threshold, typically occurred as
      oxygen fell below 5%. Mortality was observed at 2% levels. The time to obtain
      these levels of insect activity and oxygen depletion ranged from 3-14 d depending
      on initial infestation levels. Acoustic detection made it possible to estimate
      the duration required for reduction of insect activity to levels resulting in
      negligible damage to the stored product under hermetic conditions. Such
      information is of value to farmers and warehouse managers attempting to reduce
      pest damage in stored crops.

PMID- 29045683
TI  - Color Patterning in Hard Ticks (Acari: Ixodidae).
AB  - Among the hard ticks (Acari: Ixodidae), many species in the section Metastriata
      have intricate ornamentation on the scutum that is often used as a taxonomic
      character. However, the biological function(s) of this ornamentation remains
      unknown. Here, we summarize the main functions of color patterns recognized in
      the animal kingdom-thermoregulation, aposematism, camouflage, aggregation, mate
      recognition, and sexual signaling-and evaluate the potential of each of these to
      explain ornamentation in hard ticks. We also note the challenges and
      uncertainties involved in interpreting ornamentation in ticks as well as
      potential approaches for future research.

PMID- 29045684
TI  - Lean Management to support Choosing Wisely in healthcare: the first evidence from
      a systematic literature review.
AB  - Purpose: Choosing Wisely (CW) is an emergent approach to identify and reduce
      unnecessary care, such as tests and treatments that do not add value for patients
      and may even cause harm. The purpose of this paper is to investigate whether and
      how Lean Healthcare Management (LHM) can support CW objectives, focusing on
      customer needs and on waste elimination. Data sources: A systematic literature
      review has been performed in Scopus, PubMed and Web of Science. Study selection:
      Peer reviewed articles published in English language have been selected. Papers
      were considered if they regarded LHM and its possible support for achieving CW
      objectives. Data extraction. The links between the LHM purposes of adoption and
      the pursued CW objectives were investigated. Moreover, LHM tools, practices and
      interventions to support CW were grasped. Results of data synthesis: Sixteen
      articles were included in the analysis. Links between the identified LHM purposes
      of adoption and CW objectives were discovered: through process understanding,
      optimization, evaluation and control, LHM contributes to the reduction of
      overuses in healthcare, but also to the delivery of a more effective and evidence
      based care (EBC). Moreover, it provides an objective approach useful for choosing
      the most cost-effective solution among different alternatives. Conclusions:
      Results highlight how LHM, and with which tools and practices, can be adopted to
      enhance the healthcare appropriateness pursued by CW, paving the way for
      interesting future research about this emerging topic.

PMID- 29045685
TI  - MicroRNAs and complex diseases: from experimental results to computational
      models.
AB  - Plenty of microRNAs (miRNAs) were discovered at a rapid pace in plants, green
      algae, viruses and animals. As one of the most important components in the cell,
      miRNAs play a growing important role in various essential and important
      biological processes. For the recent few decades, amounts of experimental methods
      and computational models have been designed and implemented to identify novel
      miRNA-disease associations. In this review, the functions of miRNAs, miRNA-target
      interactions, miRNA-disease associations and some important publicly available
      miRNA-related databases were discussed in detail. Specially, considering the
      important fact that an increasing number of miRNA-disease associations have been
      experimentally confirmed, we selected five important miRNA-related human diseases
      and five crucial disease-related miRNAs and provided corresponding introductions.
      Identifying disease-related miRNAs has become an important goal of biomedical
      research, which will accelerate the understanding of disease pathogenesis at the
      molecular level and molecular tools design for disease diagnosis, treatment and
      prevention. Computational models have become an important means for novel miRNA
      disease association identification, which could select the most promising miRNA
      disease pairs for experimental validation and significantly reduce the time and
      cost of the biological experiments. Here, we reviewed 20 state-of-the-art
      computational models of predicting miRNA-disease associations from different
      perspectives. Finally, we summarized four important factors for the difficulties
      of predicting potential disease-related miRNAs, the framework of constructing
      powerful computational models to predict potential miRNA-disease associations
      including five feasible and important research schemas, and future directions for
      further development of computational models.

PMID- 29045686
TI  - The need for speed: the peer-review process and what are we doing about it?

PMID- 29045687
TI  - Corrigendum.

PMID- 29045688
TI  - NICE public health guidance update.

PMID- 29045689
TI  - Sensitivity to House Dust Mites Allergens with Atopic Asthma and Its Relationship
      with CD14 C(-159T) Polymorphism in Patients of West Bengal, India.
AB  - India is the home to around 15-20 million asthmatics, and asthma prevalence is
      increasing in Indian metropolitan area, including Kolkata, West Bengal. Complex
      interactions of genetic and environmental factors are involved in asthma. Genome
      wide search for susceptible loci regulating IgE response (atopy) have identified
      a candidate gene CD14 which is most important in the context of allergic
      responses of respiratory system. This study was aimed to investigate the role of
      house dust and house dust mites in development of bronchial asthma and to explore
      the possible association of candidate gene CD14 with disease manifestation among
      Kolkata patient population. Skin-prick test was done among 950 asthmatic patients
      against 8 aeroallergens, including house dust and house dust mites and total
      serum IgE and allergen-specific IgE were measured. Polymerase chain reaction
      restriction fragment length polymorphism was done in patients and nonasthmatic
      control (n = 255 in each) to characterize a functional polymorphism, C(-159)T, of
      CD14, a positional candidate gene for allergy. We identified house dust as the
      most common aeroallergen sensitizer among atopic patients in Kolkata followed by
      Dermatophagoides pteronyssinus and Dermatophagoides farinae Hughes (Acari:
      Pyroglyphidae) mites. Patient's sera contain significantly higher IgE level than
      that of control. Allergen-specific IgE antibody test revealed that 76.36%
      patients had specific IgE antibody against D. pteronyssinus mite. There was a
      significant difference in the distribution of alleles and genotypes for CD14
      polymorphism with an increase in disease severity. So, in Kolkata, house dust
      mite is a common aeroallergen and D. pteronyssinus is predominant among mites.
      The present study revealed that bronchial asthma has a genetic background.

PMID- 29045690
TI  - Clinical Characteristics of Hospitalized Infants With Laboratory-Confirmed
      Pertussis in Guatemala.
AB  - Background: Pertussis is an important cause of hospitalization and death in
      infants too young to be vaccinated (aged <2 months). Limited data on infant
      pertussis have been reported from Central America. The aim of this study was to
      characterize acute respiratory illnesses (ARIs) attributable to Bordetella
      pertussis among infants enrolled in an ongoing surveillance study in Guatemala.
      Methods: As part of a population-based surveillance study in Guatemala, infants
      aged <2 months who presented with ARI and required hospitalization were enrolled,
      and nasopharyngeal and oropharyngeal swab specimens were obtained. For this
      study, these specimens were tested for B pertussis using real-time polymerase
      chain reaction (PCR). Results: Among 301 infants hospitalized with ARI, we found
      11 with pertussis confirmed by PCR (pertussis-positive infants). Compared to
      pertussis-negative infants, pertussis-positive infants had a higher mean
      admission white blood cell count (20900 vs 12579 cells/MUl, respectively; P =
      .024), absolute lymphocyte count (11517 vs 5591 cells/MUl, respectively; P <
      .001), rate of admission to the intensive care unit (64% vs 35%, respectively; P
      = .054), and case fatality rate (18% vs 3%, respectively; P = .014). Ten of the
      11 pertussis-positive infants had cough at presentation; the majority (80%) of
      them had a cough duration of <7 days, and only 1 had a cough duration of >14
      days. Fever (temperature >= 38 degrees C) was documented in nearly half (45%) of
      the pertussis-positive infants (range, 38.0-38.4 degrees C). Conclusions: In this
      study of infants <2 months of age hospitalized with ARI in Guatemala, pertussis
      positive infants had a high rate of intensive care unit admission and a higher
      case fatality rate than pertussis-negative infants.

PMID- 29045691
TI  - Genetic dissection of Arabidopsis MAP kinase phosphatase 1-dependent PAMP-induced
      transcriptional responses.
AB  - Plant immunity is initiated by extracellular detection of pathogen-associated
      molecular patterns (PAMPs) through surface-localized pattern recognition
      receptors (PRRs). PRR activation induces many responses including the activation
      of mitogen-activated protein kinases (MAPKs) that ultimately limit bacterial
      growth. Previous work identified Arabidopsis MAP kinase phosphatase 1 (MKP1) as a
      negative regulator of signaling pathways required for some, but not all, of PAMP
      initiated responses. Specifically, loss of MAPK MPK6 in an mkp1 background
      suppressed a subset of the mkp1-dependent biological phenotypes, indicating the
      requirement for MPK6 in MKP1-dependent signaling. To further genetically separate
      the outputs of PAMP-responsive signaling pathways, we performed a transcriptome
      analysis in Arabidopsis wild type, mkp1 and mkp1 mpk6 seedlings treated with the
      bacterially derived PAMP elf26 for 0, 30, and 90 min. Using differential genetic
      and temporal clustering analyses between and within genotypes, we identified and
      separated 6963 elf26-responsive transcripts based on both genetic requirements of
      MKP1 (with or without a requirement for MPK6) and temporal transcriptional
      accumulation patterns, and some of these novel response markers were validated by
      qRT-PCR over a more extended time course. Taken together, our transcriptome
      analysis provides novel information for delineating PAMP signaling pathways.

PMID- 29045692
TI  - Seasonal Variation and Weather Changes Related to the Occurrence and Severity of
      Acute Hematogenous Osteomyelitis in Children.
AB  - Background: Acute hematogenous osteomyelitis (AHO) demonstrates regional
      variability in incidence and severity. In this study, we evaluated seasonal
      variations of AHO and assessed the effects of weather trends on the occurrence
      and severity of illness in affected children. Methods: National Weather Service
      data from the dates of symptom onset and of admission of children with AHO were
      gathered. Seasonal occurrence rates and the weather patterns were studied
      according to severity-of-illness category. Statistical analysis was performed
      with Pearson and Spearman correlations and analysis of variance. Results: A total
      of 209 children with AHO were admitted within 21 days of symptom onset (average,
      5.0 +/- 3.8 days). Severity-of-illness scores ranged from 0 to 10 (average, 3.2
      +/- 3.2). Symptom onset occurred most commonly in summer (73 [34.9%]) or spring
      (54 [25.8%]). We found a significant correlation between severity of illness and
      minimum temperature at symptom onset during the summer season (P = .020). A
      significant change in average humidity (21.6%) occurred during the winter between
      the date of symptom onset and the date of admission for children with severe
      illness (P = .020). Discussion: This study identified seasonal variation in the
      occurrence of AHO in children; summer was the most common season for occurrence.
      To our knowledge, this is the first detailed evaluation of weather parameters and
      trends in weather changes from symptom onset to admission with consideration of
      the effects of weather on the occurrence of infection and severity of illness.

PMID- 29045693
TI  - Pharmacokinetics of Ceftaroline in a Preterm Infant With Methicillin-Resistant
      Staphylococcus Aureus Pneumonia.
AB  - We report here the first pharmacokinetic-pharmacodynamic relationship for
      ceftaroline in a preterm infant born at <28 weeks' gestational age who was given
      ceftaroline (8.5 mg/kg every 8 hours) for pneumonia attributable to methicillin
      resistant Staphyloccocus aureus. This dose of ceftaroline was adequate to achieve
      the pharmacodynamic endpoint associated with efficacy for methicillin-resistant
      Staphyloccocus aureus.

PMID- 29045694
TI  - Machine learning approaches to decipher hormone and HER2 receptor status
      phenotypes in breast cancer.
AB  - Breast cancer prognosis and administration of therapies are aided by knowledge of
      hormonal and HER2 receptor status. Breast cancer lacking estrogen receptors,
      progesterone receptors and HER2 receptors are difficult to treat. Regarding large
      data repositories such as The Cancer Genome Atlas, available wet-lab methods for
      establishing the presence of these receptors do not always conclusively cover all
      available samples. To this end, we introduce median-supplement methods to
      identify hormonal and HER2 receptor status phenotypes of breast cancer patients
      using gene expression profiles. In these approaches, supplementary instances
      based on median patient gene expression are introduced to balance a training set
      from which we build simple models to identify the receptor expression status of
      patients. In addition, for the purpose of benchmarking, we examine major machine
      learning approaches that are also applicable to the problem of finding receptor
      status in breast cancer. We show that our methods are robust and have high
      sensitivity with extremely low false-positive rates compared with the well
      established methods. A successful application of these methods will permit the
      simultaneous study of large collections of samples of breast cancer patients as
      well as save time and cost while standardizing interpretation of outcomes of such
      studies.

PMID- 29045695
TI  - A New Collection of Amblyomma parvitarsum (Acari: Ixodidae) in Peru, With
      Description of a Gynandromorph and Report of Rickettsia Detection.
AB  - Adult stages of Amblyomma parvitarsum Neumann parasitize wild and domestic
      camelids of the genera Lama and Vicugna in highlands of Andean Plateau and
      Patagonia. Within the Peruvian Andes, few reports have documented this tick-host
      association, and although reported in Chile and Argentina, Rickettsia-infected A.
      parvitarsum remains undocumented for this country. Here we report a new
      collection of A. parvitarsum from Peru, the finding of the first gynandromorph
      for the species and high prevalence of Rickettsia in adult stages.

PMID- 29045696
TI  - Group Visits for Overdose Education and Naloxone Distribution in Primary Care: A
      Pilot Quality Improvement Initiative.
AB  - Objective: Opioid prescribing for chronic pain significantly contributes to
      opioid overdose deaths in the United States. Naloxone as a take-home antidote to
      opioid overdose is underutilized and has not been evaluated in the high-risk
      chronic pain population. The objective was to increase overdose education and
      naloxone distribution (OEND) to high-risk patients on long-term opioid therapy
      for pain by utilizing group visits in primary care. Design: Quality improvement
      intervention among two primary care clinics. Setting: A large, academic facility
      within the Veterans Health Administration. Subjects: Patients prescribed >=100 mg
      morphine-equivalent daily dose or coprescribed opioids and benzodiazepines.
      Methods: One clinic provided usual care with respect to OEND; another clinic
      encouraged attendance at an OEND group visit to all of its high-risk patients.
      Results: We used attendance at group visits, prescriptions of naloxone issued,
      and patient satisfaction scores to evaluate this format of OEND. Key Results:
      Group OEND visits resulted in significantly more naloxone prescriptions than
      usual care. At these group visits, patients were engaged, valued the experience,
      and all requested a prescription for the naloxone kit. Conclusion: This quality
      improvement pilot study suggests that OEND group visits are a promising model of
      care.

PMID- 29045697
TI  - Impact of Human Immunodeficiency Virus Drug Resistance on Treatment of Human
      Immunodeficiency Virus Infection in Children in Low- and Middle-Income Countries.
AB  - Children living with human immunodeficiency virus (HIV) in low- and middle-income
      countries (LMICs) experience higher rates of virologic failure than adults. Human
      immunodeficiency virus drug resistance (HIVDR) plays a major role in pediatric
      HIV treatment failure because nonsuppressive maternal antiretroviral therapy
      (ART) during pregnancy and breastfeeding as well as infant antiretroviral
      prophylaxis lead to high rates of pretreatment drug resistance to regimens most
      commonly used in children living with HIV. Lack of availability of durable,
      potent drugs in child-friendly formulations in LMICs and adherence difficulties
      contribute to acquired drug resistance during treatment. Optimizing drugs
      available for treating children living with HIV in LMICs, providing robust
      adherence support, and ensuring virologic monitoring for children receiving ART
      are essential for reducing HIVDR and improving treatment outcomes for children
      living with HIV in LMICs.

PMID- 29045698
TI  - Remission in psoriatic arthritis-where are we now?
AB  - Advances in treatments and treatment strategies for PsA have led to many patients
      responding well to management of their disease, and targeting remission as a
      treatment goal is now a possibility. Treat to target is a strategy aimed at
      maximizing benefit, irrespective of the type of medication used, by monitoring
      disease activity and using it to guide therapy. The measurement of response to
      treatment has been the subject of wide discussions among experts for some time,
      and many instruments exist. Comparisons of the different measures and their
      different strengths and weaknesses is ongoing. The impact of modern imaging
      techniques on monitoring disease progression is also evolving, and advanced
      techniques using both MRI and US have the potential to improve management of PsA
      through identification of risk factors for poor prognosis as well as accurate
      assessment of inflammation and damage, including subclinical disease. Increased
      understanding of the pathways that drive the pathogenesis of PsA will be key to
      identifying specific biomarkers for the disease and developing effective
      treatment strategies. Targets for response, considerations for use of a treat to
      target strategy in PsA, different imaging techniques and serological aspects of
      remission are all discussed in this review, and areas for further research are
      identified.

PMID- 29045699
TI  - Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza
      Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study.
AB  - Background: The impact of human immunodeficiency virus (HIV) infection on
      influenza incidence and severity in adults in sub-Saharan Africa is unclear.
      Seasonal influenza vaccination is recommended for HIV-infected persons in
      developed settings but is rarely implemented in Africa. Methods: We conducted a
      prospective cohort study to compare the incidence of laboratory-confirmed
      influenza illness between HIV-infected and HIV-uninfected adults in Blantyre,
      Malawi. In a parallel case-control study, we explored risk factors for severe
      influenza presentation of severe (hospitalized) lower respiratory tract
      infection, and mild influenza (influenza-like illness [ILI]). Results: The cohort
      study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April
      2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119
      (4.2%) in HIV-uninfected adults were positive for influenza by means of
      polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years;
      incidence rate ratio, 2.75; 95% confidence interval, 1.02-7.44; P = .03; adjusted
      for age, sex, household crowding, and food security). In the case-control study,
      influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower
      respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence
      was 69.6% and 29.6%, respectively, among influenza-positive case patients and
      controls. HIV was a significant risk factor for severe influenza (odds ratio,
      4.98; 95% confidence interval, 2.09-11.88; P < .001; population-attributable
      fraction, 57%; adjusted for season, sanitation facility, and food security).
      Conclusions: HIV is an important risk factor for influenza-associated ILI and
      severe presentation in this high-HIV prevalence African setting. Targeted
      influenza vaccination of HIV-infected African adults should be reevaluated, and
      the optimal mechanism for vaccine introduction in overstretched health systems
      needs to be determined.

PMID- 29045700
TI  - Prediction model of critical weight loss in cancer patients during particle
      therapy.
AB  - Background and purpose: The objective of this study is to investigate the
      predictors of critical weight loss in cancer patients receiving particle therapy,
      and build a prediction model based on its predictive factors. Materials and
      methods: Patients receiving particle therapy were enroled between June 2015 and
      June 2016. Body weight was measured at the start and end of particle therapy.
      Association between critical weight loss (defined as >5%) during particle therapy
      and patients' demographic, clinical characteristic, pre-therapeutic nutrition
      risk screening (NRS 2002) and BMI were evaluated by logistic regression and
      decision tree analysis. Results: Finally, 375 cancer patients receiving particle
      therapy were included. Mean weight loss was 0.55 kg, and 11.5% of patients
      experienced critical weight loss during particle therapy. The main predictors of
      critical weight loss during particle therapy were head and neck tumour location,
      total radiation dose >=70 Gy on the primary tumour, and without post-surgery, as
      indicated by both logistic regression and decision tree analysis. Prediction
      model that includes tumour locations, total radiation dose and post-surgery had a
      good predictive ability, with the area under receiver operating characteristic
      curve 0.79 (95% CI: 0.71-0.88) and 0.78 (95% CI: 0.69-0.86) for decision tree and
      logistic regression model, respectively. Conclusions: Cancer patients with head
      and neck tumour location, total radiation dose >=70 Gy and without post-surgery
      were at higher risk of critical weight loss during particle therapy, and early
      intensive nutrition counselling or intervention should be target at this
      population.

PMID- 29045701
TI  - Regulatory T Cells Contribute to HIV-1 Reservoir Persistence in CD4+ T Cells
      Through Cyclic Adenosine Monophosphate-Dependent Mechanisms in Humanized Mice In
      Vivo.
AB  - Background: Regulatory T cells (Tregs) suppress T-cell immune activation and
      human immunodeficiency virus type 1 (HIV-1) replication, but the role of Tregs in
      HIV-1 reservoir persistence is poorly defined. Methods: Tregs were depleted by
      denileukin diftitox in humanized mice with chronic HIV-1 infection. Viral
      replication in lineage cells was determined by p24 expression. Levels of HIV-1
      RNA and DNA in human cells, as well as replication-competent-virus-producing
      cells, were measured to quantified viral replication and reservoirs. Results:
      Treg depletion resulted in a blip of HIV-1 replication in T cells but not in
      myeloid cells. The major activated reservoir cells were memory CD4+ T cells in
      vivo. Interestingly, the transient activation of viral replication led to HIV-1
      reservoir reduction after viremia resuppression, as indicated by the quantity of
      HIV-1 DNA and replication-competent-virus-producing cells. Furthermore, we
      demonstrated that Tregs use cyclic adenosine monophosphate (cAMP)-dependent
      protein kinase A pathway to inhibit HIV-1 activation and replication in resting
      conventional T cells in vitro. Conclusion: Tregs suppress HIV-1 replication in T
      cells and contribute to HIV-1 reservoir persistence. cAMP produced in Tregs is
      involved in their suppression of viral gene activation and expression. Treg
      depletion combined with combination antiretroviral therapy provides a novel
      strategy for HIV-1 cure.

PMID- 29045702
TI  - The Edaphic Environment Mediates Flowering-Time Differentiation Between Adjacent
      Populations of Leptosiphon Parviflorus.
AB  - Flowering time is an important life history trait in plants that often affects
      fitness. The optimal time to flower may be influenced by trade-offs between
      flowering time and growth-related traits and is thus likely to differ among
      habitats. Because flowering-time differences between populations can also reduce
      gene flow, understanding the factors that contribute to variation in flowering
      time among closely adjacent populations that experience gene flow is of
      particular interest. Plant adaptation to different edaphic environments provides
      some of the best examples of adaptive divergence at small spatial scales, and
      often coincides with flowering-time shifts. The current study addresses the
      causes of flowering-time differences in two populations of Leptosiphon
      parviflorus that are locally adapted to adjacent serpentine and sandstone soils
      despite moderate levels of gene flow and close geographic proximity. Field
      reciprocal-transplant studies and watering manipulations in the greenhouse
      demonstrate the contribution of both the genotype and the environment to observed
      flowering-time differences. The plasticity of flowering time in response to soil
      type appears to be driven by differences in soil moisture. In addition, selection
      on flowering time was measured in both soil types across 4 years of study using a
      set of F5 advanced-generation hybrids and found to differ between the habitats.
      Therefore, both selection and plasticity contribute to flowering-time differences
      between these populations and thus have likely played an important role in the
      initiation and/or maintenance of adaptive divergence in this system.

PMID- 29045703
TI  - Reply to Skowronski et al.

PMID- 29045705
TI  - Outbreak and Eradication of Tropical Rat Mite (Acari: Macronyssidae) in a
      European Animal Facility.
AB  - A zoonotic, opportunistic out-break of tropical rat mite Ornithonyssus bacoti
      [Acari: Macronyssidae; Ornithonyssus bacoti (Hirst)] in an animal facility, is
      described. Immunocompetent mice [Mus musculus (Linnaeus)] and rat [Rattus
      norvegicus (Berkenhout)] strains in a conventional health status facility
      suffered from scratching and allopecia and staff members suffered from pruritic,
      erythemato-papular lesions, presumed to be allergic in origin. O. bacoti was
      identified and treatment with a 0.1% ivermectin solution led to its complete
      erradication. Safety assessment revealed no signs of acute toxicity in any animal
      strain. Following this inexpensive strategy, 7 wk after the initial dose, samples
      were negative for the presence of acari. At the time of this report, 26 months
      after diagnosis, O. bacoti remains undetected.

PMID- 29045704
TI  - New-onset diabetes after kidney transplantation: can the risk be modified by
      choosing immunosuppression regimen based on pretransplant viral serology?
AB  - Background: This study aimed to analyze adult kidney transplant recipients (KTRs)
      for the risk of new-onset diabetes after transplantation (NODAT) associated with
      viral serologies and immunosuppression regimens [tacrolimus (Tac) + mycophenolate
      (MPA), cyclosporine (CSA) + MPA, sirolimus (SRL) + MPA, SRL + CSA or SRL +Tac].
      Methods: Cox regression models were used to examine the risk of NODAT in the
      first posttransplant year associated with: (i) CSA + MPA, SRL + MPA, SRL + MPA or
      SRL + Tac versus reference, Tac + MPA; (ii) pretransplant viral serology [+ or -;
      hepatitis B core (HBc), hepatitis C (HCV), cytomegalovirus (CMV) or Epstein Barr
      Virus (EBV)]; and (iii) interactions between immunosuppression regimens and the
      viral serology found significant in the main analysis. Results: Adult KTRs (n =
      97 644) from January 1995 through September 2015 were studied. HCV+ [hazard ratio
      (HR) 1.50, 95% confidence interval (CI) 1.31-1.68] or CMV+ (HR 1.12, 95% CI 1.06
      1.19) serology was a risk factor and HBc+ (HR 1.04, 95% CI 0.95-1.15) or EBV+ (HR
      1.06, 95% CI 0.97-1.15) serology was not a risk factor for NODAT. Regardless of
      associated HCV or CMV serology, risk of NODAT relative to the reference regimen
      (Tac + MPA) was lower with CSA + MPA [HCV-: HR 0.74, 95% CI 0.65-0.85; HCV+: HR
      0.47, 95% CI 0.28-0.78; CMV-: CSA + MPA HR 0.68, 95% CI 0.54-0.86; CMV+: (CSA +
      MPA) HR 0.73, 95% CI 0.63-0.85] and similar with SRL + CSA or SRL + MPA. In KTRs
      with HCV- or CMV+ serology, SRL + Tac was associated with a higher risk of NODAT
      relative to reference [HCV- (HR 1.43, 95% CI 1.17-1.74) and CMV+ (HR 1.44, 95% CI
      1.14-1.81), respectively]. The risk for NODAT-free graft loss was lower with Tac
      + MPA than the other regimens. Conclusions: Tailoring immunosuppression regimen
      based on HCV or CMV serology may modify the risk of developing NODAT in KTRs.

PMID- 29045707
TI  - The social determinants of lesbian, gay, bisexual and transgender youth
      suicidality in England: a mixed methods study.
AB  - Background: Lesbian, gay, bisexual and transgender (LGBT) youth have a higher
      risk of suicidality and self-harm than heterosexual youth populations but little
      is known about the underlying mechanisms. We aimed to investigate the social
      determinants of this mental health inequality. Methods: A two-stage sequential
      mixed method study was conducted. Firstly, 29 semi-structured interviews with
      LGBT youth (aged 13-25 years old) were completed. Data was analysed thematically.
      Stage 2 involved a self-completed questionnaire employing an online community
      based sampling strategy (n = 789). Logistic regression analysis was performed to
      predict suicidality. Results: Five social determinants explained suicidal risk:
      (i) homophobia, biphobia or transphobia; (ii) sexual and gender norms; (iii)
      managing sexual and gender identities across multiple life domains; (iv) being
      unable to talk; (v) other life crises. Youth who were transgender (OR = 1.50, P <
      0.022), disabled (OR = 2.23, P < 0.000), had self-harmed (OR = 7.45, P < 0.000),
      were affected by abuse (OR = 2.14, P < 0.000), and affected by not talking about
      their emotions (OR = 2.43, P < 0.044) were most likely to have planned or
      attempted suicide. Conclusions: Public health universal interventions that tackle
      bullying and discrimination in schools, and selected interventions that provide
      specific LGBT youth mental health support could reduce LGBT mental health
      inequalities in youth suicidality.

PMID- 29045706
TI  - Kidney injury molecule-1 staining in renal allograft biopsies 10 days after
      transplantation is inversely correlated with functioning proximal tubular
      epithelial cells.
AB  - Background: Kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated
      lipocalin (NGAL) are promising biomarkers for monitoring delayed graft function
      (DGF) after kidney transplantation. Here we investigated localization and
      distribution of KIM-1 and NGAL staining in renal allograft biopsies and studied
      their association with histological features, functional DGF (fDGF) and the
      tubular function slope (TFS), a functioning proximal tubular epithelial cell
      (PTEC) marker. Methods: Day 10 protocol biopsies of 64 donation after circulatory
      death recipients were stained for KIM-1 and NGAL and the positive area was
      quantified using ImageJ software. Biopsies were scored according to Banff and
      acute tubular necrosis (ATN) criteria. A 99mtechnetium-mercaptoacetyltriglycine
      (99mTc-MAG3)-renography was performed to calculate TFS. Results: KIM-1 staining
      was located on the brush border of tubular epithelial cells (TECs) and correlated
      with denudation, while NGAL was present more focally in a cytoplasmic
      distribution. KIM-1 and NGAL staining were not correlated and no co-localization
      was observed. Quantitative stainings were not associated with fDGF, but KIM-1
      tended to be higher in patients with prolonged fDGF (>=21 days; P = 0.062). No
      correlation was observed between the quantitative tissue stainings and urinary
      KIM-1 or NGAL. Quantitative KIM-1 staining was inversely correlated with the TFS
      (Spearman's rho = -0.53; P < 0.001), whereas NGAL was not. The latter finding
      might be because cortical NGAL staining is dependent on filtration and subsequent
      reabsorption by functioning PTECs. Staining of NGAL was indeed restricted to
      PTECs, as shown by co-localization with a PTEC-specific lectin. Conclusions: KIM
      1 and NGAL staining showed different localization and distribution. Quantitative
      KIM-1 staining was inversely correlated with functioning PTECs.

PMID- 29045708
TI  - Association between polycyclic aromatic hydrocarbon exposure and peripheral blood
      mononuclear cell DNA damage in human volunteers during fire extinction exercises.
AB  - This study investigated a number of biomarkers, associated with systemic
      inflammation as well as genotoxicity, in 53 young and healthy subjects
      participating in a course to become firefighters, while wearing personal
      protective equipment (PPE). The exposure period consisted of a 3-day training
      course where the subjects participated in various live-fire training exercises.
      The subjects were instructed to extinguish fires of either wood or wood with
      electrical cords and mattresses. The personal exposure was measured as dermal
      polycyclic aromatic hydrocarbon (PAH) concentrations and urinary excretion of 1
      hydroxypyrene (1-OHP). The subjects were primarily exposed to particulate matter
      (PM) in by-stander positions, since the self-contained breathing apparatus
      effectively prevented pulmonary exposure. There was increased dermal exposure to
      pyrene (68.1%, 95% CI: 52.5%, 83.8%) and sum of 16 polycyclic aromatic
      hydrocarbons (?PAH; 79.5%, 95% CI: 52.5%, 106.6%), and increased urinary
      excretion of 1-OHP (70.4%, 95% CI: 52.5%; 106.6%) after the firefighting exercise
      compared with the mean of two control measurements performed 2 weeks before and 2
      weeks after the firefighting course, respectively. The level of Fpg-sensitive
      sites in peripheral blood mononuclear cells (PBMCs) was increased by 8.0% (95%
      CI: 0.02%, 15.9%) compared with control measurements. The level of DNA strand
      breaks was positively associated with dermal exposure to pyrene and ?PAHs, and
      urinary excretion of 1-OHP. Fpg-sensitive sites were only associated positively
      with PAHs. Biomarkers of inflammation and lung function showed no consistent
      response. In summary, the study demonstrated that PAH exposure during
      firefighting activity was associated with genotoxicity in PBMCs.

PMID- 29045709
TI  - Joint effect of physical activity and sedentary behaviour on cardiovascular risk
      factors in Chilean adults.
AB  - Background: To investigate the associations between combined categories of
      moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) with
      markers of adiposity and cardiovascular risk in adults. Methods: Overall, 5040
      participants (mean age 46.4 years and 59.3% women) from the cross-sectional
      Chilean National Health Survey 2009-2010 were included in this study. MVPA and SB
      were measured using the Global Physical Activity questionnaire. Four categories
      were computed using MVPA- and SB-specific cut-offs ('High-SB & Active', 'Low-SB &
      Active', 'High-SB & Inactive' and 'Low-SB & Inactive'). Results: Compared to the
      reference group ('High-SB & Inactive'), those in 'High-SB & Active' and 'Low-SB &
      Active' were less likely to have an obese BMI (OR: 0.67 [0.54; 0.85], P = 0.0001
      and 0.74 [0.59; 0.92] P = 0.0007, respectively) and less likely to have metabolic
      syndrome (OR: 0.63 [0.49; 0.82], P < 0.0001 and 0.72 [0.57; 0.91], P = 0.007),
      central obesity (OR: 0.79 [0.65; 0.96], P = 0.016 and 0.71 [0.59; 0.84], P <
      0.0001), diabetes (OR: 0.45 [0.35; 0.59], P < 0.0001 and 0.44 [0.34; 0.56], P <
      0.0001) and hypertension (OR: 0.52 [0.43; 0.63], P < 0.0001 and 0.60 [0.50;
      0.72], P < 0.0001), respectively. Conclusions: Being physically active and
      spending less time in SBs was associated with lower adiposity and improvements in
      cardiovascular risk factors.

PMID- 29045710
TI  - Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce
      toxicity in adults.
AB  - Radiotherapy is ubiquitous in the treatment of patients with both primary brain
      tumors as well as disease which is metastatic to the brain. This therapy is not
      without cost, however, as cognitive decline is frequently associated with cranial
      radiation, particularly with whole brain radiotherapy (WBRT). The precise
      mechanisms responsible for radiation-induced morbidity remain incompletely
      understood and continue to be an active area of ongoing research. In this
      article, we review the hypothetical means by which cranial radiation induces
      cognitive decline as well as potential therapeutic approaches to prevent,
      minimize, or reverse treatment-induced cognitive deterioration. We additionally
      review advances in imaging modalities that can potentially be used to identify
      site-specific radiation-induced anatomic or functional changes in the brain and
      their correlation with clinical outcomes.

PMID- 29045711
TI  - The endothelial prostate-specific membrane antigen is highly expressed in
      gliosarcoma and visualized by [68Ga]-PSMA-11 PET: a theranostic outlook for brain
      tumor patients?

PMID- 29045712
TI  - Hospice utilization in patients with malignant gliomas.
AB  - Background: Despite recommendations from professional organizations supporting
      early hospice enrollment for patients with cancer, little research exists
      regarding end-of-life (EOL) practices for patients with malignant glioma (MG). We
      evaluated rates and correlates of hospice enrollment and hospice length of stay
      (LOS) among patients with MG. Methods: Using the Surveillance, Epidemiology, and
      End Results (SEER)-Medicare-linked database, we identified adult patients who
      were diagnosed with MG from January 1, 2002 to December 31, 2011 and who died
      before December 31, 2012. We extracted sociodemographic and clinical data and
      used univariate logistic regression analyses to compare characteristics of
      hospice recipients versus nonrecipients. We performed multivariable logistic
      regression analyses to examine predictors of hospice enrollment >3 or >7 days
      prior to death. Results: We identified 12437 eligible patients (46% female), of
      whom 7849 (63%) were enrolled in hospice before death. On multivariable
      regression analysis, older age, female sex, higher level of education, white
      race, and lower median household income predicted hospice enrollment. Of those
      enrolled in hospice, 6996 (89%) were enrolled for >3 days, and 6047 (77%) were
      enrolled for >7 days. Older age, female sex, and urban residence were predictors
      of longer LOS (3- or 7-day minimum) on multivariable analysis. Median LOS on
      hospice for all enrolled patients was 21 days (interquartile range, 8-45 days).
      Conclusions: We identified important disparities in hospice utilization among
      patients with MG, with differences by race, sex, age, level of education, and
      rural versus urban residence. Further investigation of these barriers to earlier
      and more widespread hospice utilization is needed.

PMID- 29045714
TI  - The psychological health of remote area medics in Iraq.
AB  - Background: Remote area medics (RAMs) may be at increased risk of mental health
      difficulties. Aims: To explore the occupational experiences of RAMs to identify
      stressors and the mental health impact. Methods: Semi-structured interviews were
      conducted with six RAMs working in Iraq to gather data, which was explored using
      interpretative phenomenological analysis. Results: Three key themes emerged from
      the data (i) the experience of being remote, (ii) cultural shock and (iii) social
      support. A number of key stressors were identified, including loneliness and
      boredom, associated with being remote, and the loss of professional identity due
      to the occupational role. Three out of the six participants reported substantial
      depressive symptoms. A number of positive coping strategies were identified,
      particularly relationships with other RAMs, via instant messaging forums.
      Conclusions: RAMs experience a number of particular stressors that could put them
      at risk of depression. Adaptive coping strategies were identified; in particular,
      virtual social support. These findings should be of interest to companies which
      employ RAMs.

PMID- 29045713
TI  - SCPortalen: human and mouse single-cell centric database.
AB  - Published single-cell datasets are rich resources for investigators who want to
      address questions not originally asked by the creators of the datasets. The
      single-cell datasets might be obtained by different protocols and diverse
      analysis strategies. The main challenge in utilizing such single-cell data is how
      we can make the various large-scale datasets to be comparable and reusable in a
      different context. To challenge this issue, we developed the single-cell centric
      database 'SCPortalen' (http://single-cell.clst.riken.jp/). The current version of
      the database covers human and mouse single-cell transcriptomics datasets that are
      publicly available from the INSDC sites. The original metadata was manually
      curated and single-cell samples were annotated with standard ontology terms.
      Following that, common quality assessment procedures were conducted to check the
      quality of the raw sequence. Furthermore, primary data processing of the raw data
      followed by advanced analyses and interpretation have been performed from scratch
      using our pipeline. In addition to the transcriptomics data, SCPortalen provides
      access to single-cell image files whenever available. The target users of
      SCPortalen are all researchers interested in specific cell types or population
      heterogeneity. Through the web interface of SCPortalen users are easily able to
      search, explore and download the single-cell datasets of their interests.

PMID- 29045715
TI  - Towards precision medicine in ANCA-associated vasculitis.
AB  - ANCA-associated vasculitis (AAV) is characterized by inflammation and destruction
      of small and medium-sized vessels. Current management strategies for AAV have
      been validated in large groups of patients. However, recent insights indicate
      that distinct patient subsets may actually exist within AAV, thereby justifying
      the development of more personalized treatment strategies. In this review, we
      discuss current evidence for a better classification of AAV based on ANCA type.
      We describe how thus defined categories of AAV patients may differ in genetic
      background, clinical presentation, immune pathology, response to treatment and
      disease outcome. We also explore how these insights may provide a rationale for
      targeted treatments in different categories of AAV patients. Finally, we provide
      recommendations on how to further establish precision medicine in AAV.

PMID- 29045716
TI  - Fibromyalgia is not axial spondyloarthritis.

PMID- 29045719
TI  - Corrigenda.

PMID- 29045717
TI  - Interaction between calcium and potassium modulates elongation rate in cotton
      fiber cells.
AB  - Calcium (Ca2+) is necessary for fiber cell development in cotton (Gossypium
      hirsutum), both as a cell wall structural component and for environmental
      signaling responses. It is also known that potassium (K+) plays a critical role
      in cotton fiber cell elongation. However, it is unclear whether Ca2+ integrates
      its activities with K+ to regulate fiber elongation. Here, we report the novel
      discovery that Ca2+ deficiency, when integrated with K+ signaling, promotes fiber
      elongation. Using inductively coupled plasma-mass spectrometry (ICP-MS), we
      determined dynamic profiles of the ionome in ovules and fibers at different
      developmental stages, and found that a high accumulation of macro-elements, but
      not Ca2+, was associated with longer fibers. Using an in vitro ovule culture
      system, we found that under Ca2+-deficient conditions, sufficient K+ (52 mM)
      rapidly induced ovule and fiber browning, while reduced K+ (2 or 27 mM) not only
      suppressed tissue browning but also altered fiber elongation. Reduced K+ also
      enhanced reactive oxygen species scavenging ability and maintained abscisic acid
      and jasmonic acid levels, which in turn compensated for Ca2+ deficiency. Ca2+
      deficiency combined with reduced K+ (0 mM Ca2+ and 27 mM K+) produced longer
      fibers in cultured ovules, due to cell wall loosening by phytosulfokine (PSK),
      expansin (EXP), and xyloglucan endotransglycosylase/hydrolase (XTH), and an
      increase of the K+ content of fiber cells. Using transgenic cotton, we showed
      that the CBL-INTERACTING PROTEIN KINASE 6 (GhCIPK6) gene mediates the uptake of
      K+ under Ca2+-deficient conditions. This study establishes a new link between
      Ca2+, K+, and fiber elongation.

PMID- 29045718
TI  - Retraction Notice.

PMID- 29045720
TI  - It's arrived! Relational Autonomy Comes to Court: ABC v ST George's Healthcare
      NHS Trust [2017] EWCA 336.

PMID- 29045721
TI  - Selection Bias in the Assessment of Frailty and Its Role in Influenza Vaccine
      Effectiveness Evaluation Among Elderly Adults.

PMID- 29045722
TI  - Subjective Age and Cystatin C Among Older Adults.
AB  - Objective: Cystatin C (CysC) is a marker of kidney function that is relevant for
      the health and cognition of older adults. Little is known about the link between
      psychological factors and CysC. Therefore, the present study examined whether
      subjective age is related to CysC level and changes in CysC over time. Method:
      Participants were 5,066 individuals drawn from the Health and Retirement Study
      aged from 50 to 107 years (60% women, mean age = 69.36 years, SD = 9.54). They
      provided data on subjective age, demographic covariates, and CysC at baseline.
      CysC was assessed again 4 years later. Results: Analysis revealed that an older
      subjective age was related to higher level of CysC at baseline and to an increase
      in CysC over 4 years, controlling for demographic factors. An older subjective
      age was also related to higher risk of exceeding the clinical threshold of CysC
      at baseline and 4 years later. Additional analysis revealed that disease burden,
      depressive symptoms, physical inactivity, and BMI partly mediated these
      associations. Conclusion: The present study provides new evidence on the role of
      subjective age as a psychological factor associated with individuals' risk of
      kidney dysfunction, an association beyond chronological age.

PMID- 29045723
TI  - Acute administration of tumour necrosis factor-alpha induces spontaneous calcium
      release via the reactive oxygen species pathway in atrial myocytes.
AB  - Aims: The arrhythmogenic mechanisms of atrial fibrillation (AF) that are induced
      by acute inflammation, such as postoperative AF, are not well understood. We
      investigated the acute effects of tumour necrosis factor-alpha (TNF-alpha) that
      mimic acute inflammation on Ca2+ handling in isolated atrial myocytes and its
      underlying mechanisms. Methods and results: Cytosol Ca2+ handling and
      mitochondrial reactive oxygen species (ROS) production were studied in freshly
      isolated atrial myocytes of wild-type mice that were exposed to TNF-alpha (0.05
      ng/mL) for 2 h by Ionoptix and confocal microscopy. The acute effects of TNF
      alpha on Ca2+ handling were decreased amplitudes and prolonged decay times of
      Ca2+ transients in isolated atrial myocytes. A significant reduction in the
      sarcoplasmic reticulum (SR) Ca2+ content was detected in TNF-alpha treated cells,
      which was associated with increased spontaneous Ca2+ release events. In
      particular, physiological concentrations of TNF-alpha dramatically promoted the
      frequency of spontaneous Ca2+ waves and Ca2+ sparks, while the spark mass
      presented with reduced amplitudes and prolonged durations. The underlying
      mechanisms of pro-arrhythmic effects of TNF-alpha were further investigated.
      Acute exposure to TNF-alpha rapidly promoted mitochondrial ROS production that
      was correlated with the acute effect of TNF-alpha on Ca2+ handling, and enhanced
      the oxidation of calcium/calmodulin-dependent protein kinase II (CaMKII) and the
      phosphorylation of RyR2. However, the performance of ROS inhibitor, DL
      Dithiothreitol (DTT), reversed Ca2+ handling disorders induced by TNF-alpha.
      Conclusion: Tumour necrosis factor-alpha rapidly increases spontaneous Ca2+
      release and promotes atrial arrhythmogenesis via the ROS pathway, which suggests
      that antioxidant therapy is a promising strategy for acute inflammation related
      AF.

PMID- 29045724
TI  - Effects of Demographic History on the Detection of Recombination Hotspots from
      Linkage Disequilibrium.
AB  - In some species, meiotic recombination is concentrated in small genomic regions.
      These "recombination hotspots" leave signatures in fine-scale patterns of linkage
      disequilibrium, raising the prospect that the genomic landscape of hotspots can
      be characterized from sequence variation. This approach has led to the inference
      that hotspots evolve rapidly in some species, but are conserved in others.
      Historic demographic events, such as population bottlenecks, are known to affect
      patterns of linkage disequilibrium across the genome, violating population
      genetic assumptions of this approach. Although such events are prevalent,
      demographic history is generally ignored when making inferences about the
      evolution of recombination hotspots. To determine the effect of demography on the
      detection of recombination hotspots, we use the coalescent to simulate haplotypes
      with a known recombination landscape. We measure the ability of popular linkage
      disequilibrium-based programs to detect hotspots across a range of demographic
      histories, including population bottlenecks, hidden population structure,
      population expansions, and population contractions. We find that demographic
      events have the potential to greatly reduce the power and increase the false
      positive rate of hotspot discovery. Neither the power nor the false positive rate
      of hotspot detection can be predicted without also knowing the demographic
      history of the sample. Our results suggest that ignoring demographic history
      likely overestimates the power to detect hotspots and therefore underestimates
      the degree of hotspot sharing between species. We suggest strategies for
      incorporating demographic history into population genetic inferences about
      recombination hotspots.

PMID- 29045725
TI  - StemMapper: a curated gene expression database for stem cell lineage analysis.
AB  - Transcriptomic data have become a fundamental resource for stem cell (SC)
      biologists as well as for a wider research audience studying SC-related processes
      such as aging, embryonic development and prevalent diseases including cancer,
      diabetes and neurodegenerative diseases. Access and analysis of the growing
      amount of freely available transcriptomics datasets for SCs, however, are not
      trivial tasks. Here, we present StemMapper, a manually curated gene expression
      database and comprehensive resource for SC research, built on integrated data for
      different lineages of human and mouse SCs. It is based on careful selection,
      standardized processing and stringent quality control of relevant transcriptomics
      datasets to minimize artefacts, and includes currently over 960 transcriptomes
      covering a broad range of SC types. Each of the integrated datasets was
      individually inspected and manually curated. StemMapper's user-friendly interface
      enables fast querying, comparison, and interactive visualization of quality
      controlled SC gene expression data in a comprehensive manner. A proof-of
      principle analysis discovering novel putative astrocyte/neural SC lineage markers
      exemplifies the utility of the integrated data resource. We believe that
      StemMapper can open the way for new insights and advances in SC research by
      greatly simplifying the access and analysis of SC transcriptomic data. StemMapper
      is freely accessible at http://stemmapper.sysbiolab.eu.

PMID- 29045726
TI  - Efficacy and Safety Outcomes in Systematic Reviews of Interventions for
      Postoperative Pain in Children: Comparison Against the Recommended Core Outcome
      Set.
AB  - Objective: To investigate the range of efficacy and safety outcomes used in
      systematic reviews (SRs) of randomized controlled trials (RCTs) of interventions
      for postoperative pain in children and compare them with outcome domains
      recommended in the Pediatric Initiative on Methods, Measurement, and Pain
      Assessment in Clinical Trials (PedIMMPACT). Methods: Five electronic databases
      were searched: MEDLINE, Cochrane Database of Systematic Reviews, DARE, CINAHL,
      and PsycINFO. Two review authors extracted outcome data independently. Efficacy
      and safety outcomes were extracted and categorized. The type and number of
      outcomes were analyzed and compared against the outcomes recommended by
      PedIMMPACT. The study protocol was registered in PROSPERO (CRD42015029654).
      Results: We included 48 systematic reviews with data from 816 trials. The median
      number of all outcomes was 4, while the median number of the PedIMMPACT core
      outcomes was three out of six. The most commonly reported outcome of the
      PedIMMPACT Core Outcome set (COS) was "symptoms and adverse events," followed by
      pain intensity, which was reported in 75% of the included SRs. Just over half of
      the SRs that included a pain intensity outcome also indicated the specific pain
      assessment tool used in the methods section. Conclusions: Systematic reviews in
      the field of pediatric pain do not use the recommended COS. Nor do they
      consistently include pain as an outcome. This makes comparisons of efficacy and
      safety across interventions very difficult. Future studies should explore whether
      the authors are aware of the COS and whether the recommended COS is appropriate.

PMID- 29045727
TI  - Short-term thermal photosynthetic responses of C4 grasses are independent of the
      biochemical subtype.
AB  - C4 photosynthesis evolved independently many times, resulting in multiple
      biochemical pathways; however, little is known about how these different pathways
      respond to temperature. We investigated the photosynthetic responses of eight C4
      grasses belonging to three biochemical subtypes (NADP-ME, PEP-CK, and NAD-ME) to
      four leaf temperatures (18, 25, 32, and 40  degrees C). We also explored whether
      the biochemical subtype influences the thermal responses of (i) in vitro PEPC
      (Vpmax) and Rubisco (Vcmax) maximal activities, (ii) initial slope (IS) and CO2
      saturated rate (CSR) derived from the A-Ci curves, and (iii) CO2 leakage out of
      the bundle sheath estimated from carbon isotope discrimination. We focussed on
      leakiness and the two carboxylases because they determine the coordination of the
      CO2-concentrating mechanism and are important for parameterizing the semi
      mechanistic C4 photosynthesis model. We found that the thermal responses of Vpmax
      and Vcmax, IS, CSR, and leakiness varied among the C4 species independently of
      the biochemical subtype. No correlation was observed between Vpmax and IS or
      between Vcmax and CSR; while the ratios Vpmax/Vcmax and IS/CSR did not correlate
      with leakiness among the C4 grasses. Determining mesophyll and bundle sheath
      conductances in diverse C4 grasses is required to further elucidate how C4
      photosynthesis responds to temperature.

PMID- 29045728
TI  - How do primary care doctors in England and Wales code and manage people with
      chronic kidney disease? Results from the National Chronic Kidney Disease Audit.
AB  - Background: In the UK, primary care records are electronic and require doctors to
      ascribe disease codes to direct care plans and facilitate safe prescribing. We
      investigated factors associated with coding of chronic kidney disease (CKD) in
      patients with reduced kidney function and the impact this has on patient
      management. Methods: We identified patients meeting biochemical criteria for CKD
      (two estimated glomerular filtration rates <60 mL/min/1.73 m2 taken >90 days
      apart) from 1039 general practitioner (GP) practices in a UK audit. Clustered
      logistic regression was used to identify factors associated with coding for CKD
      and improvement in coding as a result of the audit process. We investigated the
      relationship between coding and five interventions recommended for CKD: achieving
      blood pressure targets, proteinuria testing, statin prescription and flu and
      pneumococcal vaccination. Results: Of 256 000 patients with biochemical CKD, 30%
      did not have a GP CKD code. Males, older patients, those with more severe CKD,
      diabetes or hypertension or those prescribed statins were more likely to have a
      CKD code. Among those with continued biochemical CKD following audit, these same
      characteristics increased the odds of improved coding. Patients without any
      kidney diagnosis were less likely to receive optimal care than those coded for
      CKD [e.g. odds ratio for meeting blood pressure target 0.78 (95% confidence
      interval 0.76-0.79)]. Conclusion: Older age, male sex, diabetes and hypertension
      are associated with coding for those with biochemical CKD. CKD coding is
      associated with receiving key primary care interventions recommended for CKD.
      Increased efforts to incentivize CKD coding may improve outcomes for CKD
      patients.

PMID- 29045730
TI  - Ribosomal protein NtRPL17 interacts with kinesin-12 family protein NtKRP and
      functions in the regulation of embryo/seed size and radicle growth.
AB  - We previously reported that a novel motor protein belonging to the kinesin-12
      family, NtKRP, displays critical roles in regulating embryo and seed size
      establishment. However, it remains unknown exactly how NtKRP contributes to this
      developmental process. Here, we report that a 60S ribosomal protein NtRPL17
      directly interacts with NtKRP. The phenotypes of NtRPL17 RNAi lines show notable
      embryo and seed size reduction. Structural observations of the NtRPL17-silenced
      embryos/seeds reveal that the embryo size reduction is due to a decrease in cell
      number. In these embryos, cell division cycle progression is delayed at the G2/M
      transition. These phenotypes are similar to that in NtKRP-silenced embryos/seeds,
      indicating that NtKRP and NtRPL17 function as partners in the same regulatory
      pathway during seed development and specifically regulate cell cycle progression
      to control embryo/seed size. This work reveals that NtRPL17, as a widely
      distributed ribosomal protein, plays a critical role in seed development and
      provides a new clue in the regulation of seed size. Confirmation of the
      interaction between NtKRP and NtRPL17 and their co-function in the control of the
      cell cycle also suggests that the mechanism might be conserved in both plants and
      animals.

PMID- 29045729
TI  - Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L
      have Unaffected Neuronal Migration but Display Abnormal Auditory Processing.
AB  - Developmental dyslexia is a neurodevelopmental disorder that affects reading
      ability caused by genetic and non-genetic factors. Amongst the susceptibility
      genes identified to date, KIAA0319 is a prime candidate. RNA-interference
      experiments in rats suggested its involvement in cortical migration but we could
      not confirm these findings in Kiaa0319-mutant mice. Given its homologous gene
      Kiaa0319L (AU040320) has also been proposed to play a role in neuronal migration,
      we interrogated whether absence of AU040320 alone or together with KIAA0319
      affects migration in the developing brain. Analyses of AU040320 and double
      Kiaa0319;AU040320 knockouts (dKO) revealed no evidence for impaired cortical
      lamination, neuronal migration, neurogenesis or other anatomical abnormalities.
      However, dKO mice displayed an auditory deficit in a behavioral gap-in-noise
      detection task. In addition, recordings of click-evoked auditory brainstem
      responses revealed suprathreshold deficits in wave III amplitude in AU040320-KO
      mice, and more general deficits in dKOs. These findings suggest that absence of
      AU040320 disrupts firing and/or synchrony of activity in the auditory brainstem,
      while loss of both proteins might affect both peripheral and central auditory
      function. Overall, these results stand against the proposed role of KIAA0319 and
      AU040320 in neuronal migration and outline their relationship with deficits in
      the auditory system.

PMID- 29045732
TI  - Life History Adaptations to Seasonality.
AB  - Seasonality creates a template for many natural processes and evolutionary
      adaptations. Organisms are often faced with an annual cycle consisting of a
      productive (favorable) and unproductive period. This yearly cycle along with
      other seasonal variations in abiotic factors and associated biotic interactions
      form strong selection pressures shaping the scheduling of annual activities and
      the developmental stages and modes of life through the year. Annual decisions
      impact trade-offs that involve both current and future reproductive value (RV),
      and life history theory provides the foundation to understand these linkages
      between phenology and an organism's full life. Annual routine models further
      allow for multiple annual decisions to be optimized and predicted with respect to
      lifetime consequences. Studies of life history adaptations to seasonality are
      concerned with questions such as: within the productive season, should growth
      come first, followed by reproduction, or the other way around? What is the best
      time to diapause or migrate, and how will this timing impact other life history
      traits? Should energy reserves be built, to transfer resources from 1 year to the
      next, and allow for the spatial and temporal freedom of capital breeding? If
      offspring value is low during parts of the productive season, what is then the
      best alternative to reproduction: accumulate stores, grow, or wait in safety? To
      help answer these and other questions, I provide an overview of key theoretical
      concepts and some of the main life schedules, annual routines, and trade-offs
      involved. Adaptations to the unproductive period include diapause (dormancy),
      embryonic resting stages (eggs, seeds), energy reserves, and seasonal migrations.
      Adaptations to the productive window include rapid growth, high reproductive
      effort, capital breeding, and reproduction entrained to the annual cycle and with
      precise timing. Distinct annual routines, large body size, energy storage
      capacities, and parental care are also adaptations to seasonality. Phenotypic
      plasticity and state-dependence are important parts of these traits and are
      adaptations in their own. I give particular attention to timing of breeding and
      the associated birth-time dependent contributions to fitness. Seasonality in
      offspring value impacts the scheduling of growth, storage, and reproduction and
      may create parent-offspring conflicts over breeding timing. A combined offspring
      and parent value perspective should be adopted more broadly, also because of the
      management implications. I further argue for strategic but careful use of
      latitudinal (and altitudinal) gradients, and more attention to the role of
      seasonally varying predation risk as a selective force.

PMID- 29045733
TI  - Effect of first cannulation time and dialysis machine blood flows on survival of
      arteriovenous fistulas.
AB  - Background: To study the effect of cannulation time on arteriovenous fistula
      (AVF) survival. Methods. Analysis of two prospective databases of access
      operations and dialysis sessions from 12 January 2002 through 4 January 2015 with
      follow-up until 4 January 2016. First cannulation time (FCT), defined from
      operation to first cannulation, was categorized as <2 weeks, 2-4 weeks, 4-8
      weeks, 8-16 weeks and >=16 weeks. Early cannulation was defined as FCT within 4
      weeks. AVF survival was defined as the date until the AVF was abandoned. Maximum
      machine blood flow rate (BFR) for the first 29 dialysis sessions on AVF was
      analysed. Results: Altogether, 1167 AVF with functional dialysis use were
      analysed: 667 (57%) radial cephalic AVF, 383 (33%) brachiocephalic AVF and 117
      (10%) brachiobasilic AVF. The 631 (54%) AVF created in on-dialysis patients were
      analysed separately from 536 (46%) AVF created in pre-dialysis patients. AVF
      survival was similar between cannulation categories for both pre-dialysis
      patients (P = 0.19) and on-dialysis patients (P = 0.83). Early cannulation was
      associated with similar AVF survival in both pre-dialysis patients (P = 0.82) and
      on-dialysis patients (P = 0.17). Six consecutive successful cannulations from the
      start were associated with improved AVF survival (P = 0.0002). A below-median BFR
      at the start of dialysis was associated with better AVF survival (P < 0.0001). A
      below-median increase in BFR in the first 2 months was associated with worse AVF
      survival (P = 0.007). The type of AVF, diabetes, pre-dialysis state at operation
      and six successful cannulations from the start were independent predictors for
      AVF survival. Conclusions: FCT is not associated with AVF survival. Failures to
      achieve six successful cannulations from the start of dialysis and higher machine
      BFR in the first week of dialysis are associated with decreased AVF survival.

PMID- 29045734
TI  - The Effect of Aging on Response Congruency in Task Switching: A Meta-Analysis.
AB  - Objectives: Response-congruency effects in task switching are the observed
      slowing of response times (RTs) for incongruent targets which afford more than
      one response (depending on task) in comparison to congruent stimuli that afford
      just one response regardless of the task. These effects are thought to reflect
      increased ambiguity during response selection for incongruent stimuli. Methods:
      The present study presents a meta-analysis of 27 conditions (from 16 separate
      studies) whose designs allowed investigation of age-related differences in
      response-congruency effects on RT. Results: Multilevel modelling of Brinley plots
      and state-trace plots showed no age-related effect on response congruency beyond
      that which can be explained by general age-related slowing. Discussion: The
      results add to the growing body of evidence of no age-related decline in measures
      of attention and executive functioning.

PMID- 29045735
TI  - Seasonal Variation and Dengue Burden in Paediatric Patients in New Delhi.
AB  - Objective: We conducted a study to find a relationship between main weather
      parameters with admission of positive dengue cases in a tertiary hospital.
      Methods: Retrospective analysis was undertaken to identify epidemiological trend
      of dengue in 2016 from paediatric wards of a tertiary hospital in New Delhi. Data
      were collected on patient particulars and daily weather from January to December
      2016. Results: A total of 266 confirmed cases of dengue were considered. Relative
      humidity (RH) was associated with burden of positive dengue cases. On week-wise
      analysis, each surge of dengue admission was preceded by heavy rain 4-6 weeks
      earlier. Monthly averaged daily temperature range and RH were noted to have
      strong correlations with dengue burden, keeping an interval of 2 months in
      between. Conclusions: Weather parameters seem to influence magnitude of dengue
      epidemic, particularly in dengue season. There is need to have an in-depth study
      about developing a prediction model for dengue epidemic.

PMID- 29045731
TI  - The Chimpanzee Model of Viral Hepatitis: Advances in Understanding the Immune
      Response and Treatment of Viral Hepatitis.
AB  - Chimpanzees (Pan troglodytes) have contributed to diverse fields of biomedical
      research due to their close genetic relationship to humans and in many instances
      due to the lack of any other animal model. This review focuses on the
      contributions of the chimpanzee model to research on hepatitis viruses where
      chimpanzees represented the only animal model (hepatitis B and C) or the most
      appropriate animal model (hepatitis A). Research with chimpanzees led to the
      development of vaccines for HAV and HBV that are used worldwide to protect
      hundreds of millions from these diseases and, where fully implemented, have
      provided immunity for entire generations. More recently, chimpanzee research was
      instrumental in the development of curative therapies for hepatitis C virus
      infections. Over a span of 40 years, this research would identify the causative
      agent of NonA,NonB hepatitis, validate the molecular tools for drug discovery,
      and provide safety and efficacy data on the therapies that now provide a rapid
      and complete cure of HCV chronic infections. Several cocktails of antivirals are
      FDA approved that eliminate the virus following 12 weeks of once-per-day oral
      therapy. This represents the first cure of a chronic viral disease and, once
      broadly implemented, will dramatically reduce the occurrence of cirrhosis and
      liver cancer. The recent contributions of chimpanzees to our current
      understanding of T cell immunity for HCV, development of novel therapeutics for
      HBV, and the biology of HAV are reviewed. Finally, a perspective is provided on
      the events leading to the cessation of the use of chimpanzees in research and the
      future of the chimpanzees previously used to bring about these amazing
      breakthroughs in human healthcare.

PMID- 29045736
TI  - Clinical trial parameters that influence outcomes in lupus trials that use the
      systemic lupus erythematosus responder index.
AB  - Objective: The SLE Responder Index (SRI) is a composite endpoint used in SLE
      trials. This investigation examined the clinical trial elements that drive
      response measured by the SRI. Methods: Analyses are based on data from two phase
      3 trials (n = 2262) that evaluated the impact of an anti-B-cell activating factor
      antibody on disease activity using SRI-5 as the primary endpoint
      (ClinicalTrials.gov NCT01196091 and NCT01205438). Results: The SRI-5 response
      rate at week 52 for all patients was 32.8%. Non-response due to a lack of SLEDAI
      improvement, concomitant medication non-compliance or dropout was 31, 16.5 and
      19.1%, respectively. Non-response due to deterioration in BILAG or Physician's
      Global Assessment after SLEDAI improvement, concomitant medication compliance and
      trial completion was 0.5%. Disease activity in three SLEDAI organ systems was
      highly prevalent at baseline: mucocutaneous, 90.6%; musculoskeletal, 82.9%; and
      immunologic, 71.6%. Disease activity in each of the other organ systems was <11%
      of patients. Four clinical manifestations were highly prevalent at baseline:
      arthritis, 82.6%; rash, 69.2%; alopecia, 58.2%; and mucosal ulcer, 32.5%. The
      combined prevalence of renal, vascular and CNS disease at baseline was 17.6%;
      these patients had high SRI-5 response rates. Adjustments to corticosteroids were
      allowed during the first 24 weeks. Increases in corticosteroids above 2.5 mg/day
      were observed in 16.2% of placebo patients over the first 24 weeks after
      randomization. Conclusion: The primary drivers of SRI-5 response were SLEDAI
      improvement, concomitant medication adherence and trial completion. Arthritis,
      rash, alopecia and mucosal ulcer were the most prevalent clinical manifestations
      at baseline. Corticosteroid increases and rare, highly weighted disease
      manifestations in SLEDAI can confound the SRI signal.

PMID- 29045737
TI  - Comparative Analysis of Gut Microbiota of Culex restuans (Diptera: Culicidae)
      Females From Different Parents.
AB  - The potential for gut microbiota to impede or enhance pathogen transmission is
      well-documented but the factors that shape this microbiota in mosquito vectors
      are poorly understood. We characterized and compared the gut microbiota of adult
      females of Culex restuans (Theobald; Diptera: Culicidae) from different parents.
      Cx. restuans larvae from nine field-collected egg rafts were reared on a common
      diet and gut microbiota of newly emerged adult females characterized by MiSeq
      sequencing of the V4 hypervariable region of the 16S rRNA gene. Bacterial
      diversity and evenness in individuals from one egg raft were significantly lower
      compared to those of three of the other eight egg rafts. The gut microbiota of
      adult females reared from seven of the nine egg rafts clustered together
      suggesting that individuals from most egg rafts had similar profiles of gut
      microbiota. These findings suggest that the microbiota of adult females from the
      same parents do not differ appreciably from the microbiota of adult females from
      different parents. However, additional studies using mosquitoes separated by
      geographic distances greater than those studied here and estimating the genetic
      distances between populations from different egg rafts are needed to provide
      further insights into the influence of host genetics on gut microbiota. Also
      worthwhile are studies evaluating how individuals from different egg rafts and
      harboring different gut microbiota compare in relation to vector competence for
      different pathogens.

PMID- 29045738
TI  - The proposed role of ultrasound in the management of giant cell arteritis in
      routine clinical practice.
AB  - Objective: To develop and explore a protocol for using colour duplex sonography
      (CDS) in the routine care of GCA. Methods: We tested CDS of temporal arteries and
      axillary arteries (AXs) on consecutive patients with suspected or established
      GCA, between July 2014 and September 2016. Results: We assessed 293 patients [age
      72 (10), female/male 196/97], of whom 118 had clinically confirmed GCA. Seventy
      three percent of patients had already received high-dose glucocorticoids (GCs)
      for 17 (33) days. Among new referrals with <7 days of GC treatment (n = 55), the
      sensitivity of CDS was 63.3% (95% CI: 44%, 80%), specificity 100% (95% CI: 83%,
      100%), positive predictive value 100% and negative predictive value 64.5% (95%
      CI: 53%, 74%). Sensitivity rose to 81.8% in patients with jaw claudication and
      high inflammatory markers. During the observation period, the rate of temporal
      artery biopsies decreased from 72 (42%) to 36 (25%) (P = 0.002). CDS was positive
      in 21% of 89 follow-up scans in asymptomatic individuals, compared with 37% in
      patients experiencing clinical flares. Over time, the number of halos reduced;
      only new or flaring patients showed a halo in four or more sites. The diameter of
      axillary halos reduced from referral [1.6 (0.4) mm] to follow-up [1.4 (0.2) mm, P
      = 0.01] or flares [1.4 (0.2) mm, P = 0.02]. Conclusion: CDS provides high
      positive predictive value for diagnosing GCA and allows for a significant
      reduction in temporal artery biopsies. We explored the role of CDS in detecting
      flares and demonstrated a relationship to the extent of the distribution of
      halos, but not to their size.

PMID- 29045740
TI  - Adding vancomycin to perioperative prophylaxis decreases deep sternal wound
      infections in high-risk cardiac surgery patients.
AB  - OBJECTIVES: Perioperative prophylaxis with cephalosporins reduces sternal wound
      infections (SWIs) after cardiac surgery. However, more than 50% of coagulase
      negative staphylococci, an important pathogen, are cephalosporin resistant. The
      aim of this study was to determine the impact of adjunctive vancomycin on SWIs in
      high-risk patients. METHODS: We conducted a pre- and postintervention study in an
      academic hospital. Preintervention (2010-2011), all patients received prophylaxis
      with 1.5 g of cefuroxime for 48 h. During the intervention period (2012-2013),
      high-risk patients additionally received 1 g of vancomycin. High-risk status was
      defined as body mass index <=18 or >= 30 kg/m2, reoperation, renal failure,
      diabetes mellitus, chronic obstructive pulmonary disease or immunosuppressive
      medication. Time series analysis was performed to study SWI trends and logistic
      regression to determine the effect of adding vancomycin adjusting for high-risk
      status. RESULTS: A total of 3902 consecutive patients (n = 1915 preintervention
      and n = 1987 postintervention) were included, of which 1493 (38%) patients were
      high-risk patients. In the high-risk group, 61 of 711 (8.6%) patients had SWI
      before and 30 of 782 (3.8%) patients after the intervention. Focusing on deep SWI
      (DSWI), 33 of 711 (4.6%) patients had DSWI before and 13 of 782 (1.7%) patients
      afterwards; the absolute risk difference of 2.9% yielded a number-needed-to-treat
      of 34 to prevent 1 DSWI. Corrected for high-risk status, adding vancomycin
      significantly reduced the overall SWI rate (odds ratio 0.42, 95% confidence
      interval 0.26-0.67; P < 0.001) and the subset of DSWI (odds ratio 0.30, 95%
      confidence interval 0.14-0.62; P = 0.001). The rate of SWI in low-risk patients
      remained unchanged. CONCLUSIONS: Adding vancomycin to standard antibiotic
      prophylaxis in high-risk patients significantly reduced DSWI after cardiac
      surgery.

PMID- 29045739
TI  - Assessment of Ketamine Binding of the Serotonin Transporter in Humans with
      Positron Emission Tomography.
AB  - Background: Comprehensive description of ketamine's molecular binding profile
      becomes increasingly pressing as use in real-life patient cohorts widens. Animal
      studies attribute a significant role in the substance's antidepressant effects to
      the serotonergic system. The serotonin transporter is a highly relevant target in
      this context, because it is central to depressive pathophysiology and treatment.
      This is, to our knowledge, the first study investigating ketamine's serotonin
      transporter binding in vivo in humans. Methods: Twelve healthy subjects were
      assessed twice using [11C]DASB positron emission tomography. A total of 0.50
      mg/kg bodyweight ketamine was administered once i.v. prior to the second positron
      emission tomography scan. Ketamine plasma levels were determined during positron
      emission tomography. Serotonin transporter nondisplaceable binding potential was
      computed using a reference region model, and occupancy was calculated for 4
      serotonin transporter-rich regions (caudate, putamen, thalamus, midbrain) and a
      whole-brain region of interest. Results: After administration of the routine
      antidepressant dose, ketamine showed <10% occupancy of the serotonin transporter,
      which is within the test-retest variability of [11C]DASB. A positive correlation
      between ketamine plasma levels and occupancy was shown. Conclusions: Measurable
      occupancy of the serotonin transporter was not detectable after administration of
      an antidepressant dose of ketamine. This might suggest that ketamine binding of
      the serotonin transporter is unlikely to be a primary antidepressant mechanism at
      routine antidepressant doses, as substances that facilitate antidepressant
      effects via serotonin transporter binding (e.g., selective serotonin reuptake
      inhibitors) show 70% to 80% occupancy. Administration of high-dose ketamine is
      widening. Based on the positive relationship we find between ketamine plasma
      levels and occupancy, there is a need for investigation of ketamine's serotonin
      transporter binding at higher doses.

PMID- 29045741
TI  - Respiratory Syncytial Virus Genotypes, Host Immune Profiles, and Disease Severity
      in Young Children Hospitalized With Bronchiolitis.
AB  - Background: Data on how respiratory syncytial virus (RSV) genotypes influence
      disease severity and host immune responses is limited. Here, we characterized the
      genetic variability of RSV during 5 seasons, and evaluated the role of RSV
      subtypes, genotypes, and viral loads in disease severity and host transcriptional
      profiles. Methods: A prospective, observational study was carried out, including
      a convenience sample of healthy infants hospitalized with RSV bronchiolitis.
      Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and
      blood samples for transcriptome analyses were obtained within 24 hours of
      hospitalization. Multivariate models were constructed to identify virologic and
      clinical variables predictive of clinical outcomes. Results: We enrolled 253
      infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections
      predominated over RSV B and showed greater genotype variability. RSV A/GA2,
      A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or
      BA, infants with GA5 infections had higher viral loads. GA5 infections were
      associated with longer hospital stay, and with less activation of interferon and
      increased overexpression of neutrophil genes. Conclusions: RSV A infections were
      more frequent than RSV B, and displayed greater variability. GA5 infections were
      associated with enhanced disease severity and distinct host immune responses.

PMID- 29045742
TI  - White Leaf and Panicle 2, encoding a PEP-associated protein, is required for
      chloroplast biogenesis under heat stress in rice.
AB  - The plastid-encoded RNA polymerase (PEP) plays an important role in the
      transcription machinery of mature chloroplasts, yet details of its function
      remain elusive in rice. Here, we identified a novel PEP-associated protein (PAP),
      WLP2, based on its two allelic white leaf and panicle mutants, wlp2s and wlp2w.
      The two mutants were albino lethal at high temperatures and showed decreased
      chlorophyll accumulation, abnormal chloroplast ultrastructure, and attenuated
      photosynthetic activity. Map-based cloning suggested that WLP2 encodes a putative
      pfkB-type carbohydrate kinase family protein, which is homologous to fructokinase
      like 1 (AtFLN1) in Arabidopsis. WLP2 is mainly expressed in green tissues and its
      protein localizes in chloroplasts. Expression levels of PEP-encoded genes,
      chloroplast development genes and photosynthesis-related genes were compromised
      in wlp2 mutants, indicating that WLP2 is essential for normal chloroplast
      biogenesis. Moreover, WLP2 and its paralog OsFLN2 can physically interact with
      thioredoxin OsTRXz to form a TRX-FLN regulatory module, which not only regulates
      transcription of the PEP-encoded genes but also maintains the redox balance in
      chloroplasts under heat stress. Furthermore, the wlp2w mutant gene represents a
      potential advantage in enhancing seed purity and high-throughput breeding. Our
      results strongly indicate that WLP2 protects chloroplast development from heat
      stress via a TRX-FLN regulatory module in rice.

PMID- 29045743
TI  - Sustainable Production of Fine Chemicals and Materials Using Nontoxic Renewable
      Sources.
AB  - Due to declining hydrocarbon resources and strengthening environmental
      regulations, significant attention is directed toward sustainable and nontoxic
      supplies for the development of green technologies in a variety of industries.
      This account provides an overview on the sources and recent applications of such
      materials surveying the most common nontoxic and renewable resources that can be
      obtained from biological sources. Developing a broad array of technologies based
      on these materials would establish a truly sustainable green chemical industry.
      The study thematically discusses various compound groups, eg, carbohydrates,
      proteins, and triglycerides (oils). Since often the monomers or building blocks
      of these biopolymers are of significant importance and produced in large amounts,
      the applications of these compounds are also reviewed.

PMID- 29045744
TI  - Developmental Differences Between Schizophrenia and Bipolar Disorder.
AB  - Ample evidence supports a neurodevelopmental origin in some cases of
      schizophrenia (SZ). More inconsistent information is available for bipolar
      disorder (BD). We herein review studies with a focus on premorbid (adjustment and
      functionality) and early developmental milestones that include both SZ and BD
      patients. A search was performed in the PubMed electronic database, retrieving
      619 abstracts; 30 were ultimately included in this systematic review. Eight
      prospective cohorts, 15 retrospective studies, and 7 studies based on national
      registries. Psychomotor developmental deviations and general adjustment problems
      characterize the childhood of subjects later diagnosed with SZ or BD; they are
      more marked in those later diagnosed with SZ vs BD, earlier onset vs later onset,
      and psychotic vs nonpsychotic disorders. Cognitive impairment follows a linear
      risk trend for SZ and a U-shaped trend for BD. Social isolation and
      visuoperceptual/reading anomalies more frequently antecede SZ. Pervasive
      developmental disorders increase the risk for both SZ and BD, more so in cases
      with normal intelligence. The predictive risk of each isolated developmental
      marker is low, but a significant percentage of subjects with SZ and a minority of
      adults with BD showed signs of premorbid abnormalities in childhood. The great
      limitation is still the lack of studies comparing SZ and BD that include
      psychotic and nonpsychotic bipolar cases separately. There are many cases, even
      in childhood/adolescent SZ, where no premorbid anomalies are found, and
      immunological disorders or other etiologies should be searched for. At least in
      cases with clear neurodevelopmental markers, rare genetic variants should be
      investigated.

PMID- 29045745
TI  - Long-Term Oral Appliance Therapy Improves Daytime Function and Mood in Upper
      Airway Resistance Syndrome Patients.
AB  - Objectives: To evaluate the long-term effects of an oral appliance on clinical
      symptoms, respiratory sleep parameters, sleep quality, and sustained attention in
      patients with upper airway resistance syndrome (UARS) were compared with placebo.
      Methods: This study was a randomized placebo-controlled clinical trial. Thirty
      UARS patients were randomized in two groups: placebo and mandibular advancement
      device (MAD) groups. UARS criteria were presence of sleepiness (Epworth
      Sleepiness Scale >= 10) and/or fatigue (Modified Fatigue Impact Scale >= 38)
      associated with an apnea/hypopnea index <= 5 and a respiratory disturbance index
      (RDI) > 5 events/hour of sleep, and/or flow limitation in more than 30% of total
      sleep time. All patients completed the Pittsburgh Sleep Quality Index (PSQI), the
      Functional Outcomes of Sleep Questionnaire, the Beck Anxiety and Depression
      Inventories, underwent full-night polysomnography, multiple sleep latency test,
      and Psychomotor Vigilance Test (PVT). Evaluations were performed before and after
      1.5 years of treatment. Results: RDI, number of respiratory effort-related
      arousal, percentage of total sleep time with flow limitation, and arousal index
      significantly decreased after 1.5 years of MAD treatment. PSQI total score
      improved, severity of depression symptoms decreased, and mean reaction time in
      the PVT, based on the first measurement taken at 8:00 am, significantly decreased
      (p = .03) at the end of the protocol. Conclusions: The MAD was effective in
      decreasing respiratory events in UARS patients. For UARS, 1.5 years of oral
      appliance therapy also improved sleep quality and sustained attention, and
      decreased the severity of depression symptoms. Clinical Trial: Efficacy of Oral
      Appliance for Upper Airway Resistance Syndrome: Randomized, Parallel, Placebo
      Controlled Study, NCT02636621.

PMID- 29045746
TI  - From the Cover: Identification of Natural Products as Inhibitors of Human Organic
      Anion Transporters (OAT1 and OAT3) and Their Protective Effect on Mercury-Induced
      Toxicity.
AB  - Mercury accumulates in kidneys and produces acute kidney injury. Semen cassiae
      (SC), a widely consumed tea and herbal medicine in Eastern Asia, has been
      reported to have protective effects on kidneys. In this study, SC extract was
      shown to almost abolish the histological alterations induced by mercuric chloride
      in rat kidneys. A total of 22 compounds were isolated from SC, and 1,7,8-methoxyl
      2-hydroxyl-3-methyl-anthraquinone was detected in SC for the first time. Among
      the eight compounds identified in the blood of rats after SC treatment, six were
      strong inhibitors of human organic anion transporter 1 and 3 (OAT1 and OAT3).
      Inhibitory studies revealed that OAT1 and OAT3 were inhibited by SC constituents,
      in both a competitive and noncompetitive manner. Both OAT1- and OAT3
      overexpressing cells were susceptible to the cytotoxicity of the cysteine-mercury
      conjugate, but only OAT1-overexpressing cells could be protected by 200 MUM
      probenecid or 10 MUM of the eight inhibitors in SC, suggesting that OAT1 is the
      major determinant in the cellular uptake of mercury. To facilitate the
      identification of inhibitors of OAT1 and OAT3, models of OAT1 and OAT3 were
      constructed using recently determined protein templates. By combining in silico
      and in vitro methods, inhibitors of OAT1 and OAT3 were predicted and validated
      from SC constituents. Collectively, the present study suggests that additional
      inhibitors of OAT1 and OAT3 can be predicted and validated from natural products
      by combining docking and in vitro screening, and could be a source of
      pharmaceutical compounds for developing treatments for mercury-induced kidney
      injury.

PMID- 29045747
TI  - Extracorporeal membrane oxygenation support for right ventricular failure after
      left ventricular assist device implantation.
AB  - OBJECTIVES: Right ventricular (RV) failure complicating left ventricular assist
      device implantation is associated with increased mortality. Despite a lack of
      supporting evidence, venoarterial extracorporeal membrane oxygenation (ECMO)
      support is increasingly being used as an alternative to traditional temporary RV
      support. We report our institutional experience with ECMO-facilitated RV support
      after left ventricular assist device implantation. METHODS: We retrospectively
      reviewed the concept of temporary ECMO support for perioperative RV failure in 32
      consecutive left ventricular assist device (mean age 52 +/- 14 years; male 84.4%;
      ischaemic cardiomyopathy 40.6%; INTERMACS Level I 71.8%; INTERMACS Level II 6.3%;
      INTERMACS Level III 12.5%; INTERMACS Level IV-VII 9.4%; HeartWare ventricular
      assist device 75%; HeartMate II: 25%) from May 2009 to April 2014. The study end
      points were RV recovery during ECMO support, mortality and causes of death.
      RESULTS: Twenty-nine (90.6%) patients were successfully weaned from ECMO support
      after RV recovery. Three (9.4%) patients expired during ECMO support. ECMO
      support improved RV function and haemodynamic parameters (central venous pressure
      13 mmHg vs 10 mmHg, P < 0.01; mean pulmonary artery pressure 28 mmHg vs 21 mmHg,
      P < 0.01; cardiac output 5.1 l/min vs 5.9 l/min, P = 0.09) over a median period
      of 3 (range 1-15) days. Thirty-day and in-hospital mortality were 18.8% and 25%,
      respectively. One-year survival was 75%, causes of death were multiorgan
      dysfunction syndrome (50%), sepsis (25%), haemorrhagic stroke (12.5%) and
      ischaemic stroke (12.5%). Causes of death during ECMO support were ischaemic
      stroke, sepsis and multiorgan dysfunction syndrome. CONCLUSIONS: Temporary ECMO
      facilitated RV support is associated with good long-term outcomes and high rates
      of RV recovery.

PMID- 29045749
TI  - Immune checkpoint inhibitor-related myocarditis.
AB  - Immune checkpoint inhibitors have demonstrated significant clinical benefit in
      many cancers. The clinical benefit afforded by these treatments can be
      accompanied by a unique and distinct spectrum of adverse events. Recently,
      several fatal cases of immune checkpoint inhibitor-related myocarditis were
      reported. Although its frequency is comparatively lower than that of other immune
      related adverse events, myocarditis can lead to circulatory collapse and lethal
      ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4
      (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in
      establishing peripheral tolerance to the heart. Evidence from studies using
      genetically engineered mouse models suggests that CTLA-4 signaling terminates
      proliferation and promotes anergy during the primary response to cardiac self
      peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the
      peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic
      state. Patients affected by immune checkpoint inhibitor-related myocarditis often
      experience rapid onset of profound hemodynamic compromise progressing to
      cardiogenic shock. Early diagnosis is mandatory to address specific therapy and
      correct the timing of circulatory support. However, the diagnosis of myocarditis
      is challenging due to the heterogeneity of clinical presentations. Owing to its
      early onset, nonspecific symptomatology and fulminant progression, especially
      when these drugs are used in combination, oncologists should be vigilant for
      immune checkpoint inhibitor-related myocarditis. With many questions yet to be
      answered, from basic immune biology to clinical management, future research
      should aim to optimize the use of these drugs by identifying predictive
      biomarkers of either a response to therapy or the risks of myocarditis
      development.

PMID- 29045748
TI  - Conserved asymmetry underpins homodimerization of Dicer-associated double
      stranded RNA-binding proteins.
AB  - Double-stranded RNA-binding domains (dsRBDs) are commonly found in modular
      proteins that interact with RNA. Two varieties of dsRBD exist: canonical Type A
      dsRBDs interact with dsRNA, while non-canonical Type B dsRBDs lack RNA-binding
      residues and instead interact with other proteins. In higher eukaryotes, the
      microRNA biogenesis enzyme Dicer forms a 1:1 association with a dsRNA-binding
      protein (dsRBP). Human Dicer associates with HIV TAR RNA-binding protein (TRBP)
      or protein activator of PKR (PACT), while Drosophila Dicer-1 associates with
      Loquacious (Loqs). In each case, the interaction involves a region of the protein
      that contains a Type B dsRBD. All three dsRBPs are reported to homodimerize, with
      the Dicer-binding region implicated in self-association. We report that these
      dsRBD homodimers display structural asymmetry and that this unusual self
      association mechanism is conserved from flies to humans. We show that the core
      dsRBD is sufficient for homodimerization and that mutation of a conserved leucine
      residue abolishes self-association. We attribute differences in the self
      association properties of Loqs, TRBP and PACT to divergence of the composition of
      the homodimerization interface. Modifications that make TRBP more like PACT
      enhance self-association. These data are examined in the context of miRNA
      biogenesis and the protein/protein interaction properties of Type B dsRBDs.

PMID- 29045750
TI  - Aging and HIV-Related Caregiving in Sub-Saharan Africa: A Social Ecological
      Approach.
AB  - Background and Objectives: We reviewed the literature on older adults (OAs) who
      are caring for persons living with HIV/AIDS in sub-Saharan Africa (SSA), with the
      goal of adapting models of caregiver stress and coping to include culturally
      relevant and contextually appropriate factors specific to SSA, drawing on both
      life course and cultural capital theories. Research Design and Methods: A
      systematic literature search found 81 articles published between 1975 and 2016
      which were reviewed using a narrative approach. Primary sources of articles
      included electronic databases and relevant WHO websites. Results: The main
      challenge of caregiving in SSA reflects significant financial constraints,
      specifically the lack of necessities such as food security, clean water, and
      access to health care. Caregiving is further complicated in SSA by serial bouts
      of caring for multiple individuals, including adult children and grandchildren,
      in the context of high levels of stigma associated with HIV. Factors promoting
      caregiver resilience included spirituality, bidirectional (reciprocal)
      caregiving, and collective coping strategies. Discussion and Implications: The
      creation of a theoretical model of caregiving which focuses more broadly on the
      sociocultural context of caregiving could lead to new ways of developing
      interventions in low-resources communities.

PMID- 29045751
TI  - Development and Validation of a Multidimensional Intergenerational Relationship
      Quality Scale for Aging Chinese Parents.
AB  - Background and Objectives: The quality of intergenerational relationships is
      crucial for maintaining the well-being of parents and adult children. This study
      developed and validated an Intergenerational Relationship Quality Scale for Aging
      Chinese Parents (IRQS-AP) based on the solidarity, conflict, and ambivalence
      models. Research Design and Methods: The data were derived from a cross-sectional
      study in Hong Kong which included a random sample of 1,001 community-dwelling
      individuals aged >=50 years. Exploratory factor analysis (EFA) and confirmatory
      factor analysis (CFA) were performed to examine the factor structure of the
      scale. The internal consistency reliability and convergent validity of the scale
      were also assessed. Results: EFA resulted in a 13-item four-factor (i.e.,
      consensual-normative solidarity, structural-associational solidarity, affectual
      closeness, and intergenerational conflict) model, which was supported by the CFA
      and explained 70.7% of the total variance. The reliability of the scale measured
      using Cronbach's alpha was .776. The convergent validity of the IRQS-AP was
      established by its significant correlation with depressive symptoms (r = -.385),
      sense of loneliness (r = -.449), and self-image (r = .384). Discussion and
      Implications: The IRQS-AP as a reliable and valid scale can enable researchers
      and service practitioners to measure the relationship quality between older
      people and their adult children accurately, inform the development of
      interventions to strengthen intergenerational relationships in target domains,
      and evaluate the effectiveness of related services.

PMID- 29045752
TI  - Genome size and sensitivity to DNA damage by X-rays-plant comets tell the story.
AB  - Among several factors affecting radiation sensitivity, genome size has received
      limited attention during the last 50 years since research at Brookhaven National
      Laboratory (USA) and other locations demonstrated substantial differences in
      radiation sensitivities, e.g. between tree species with large (e.g. conifers such
      as pines) versus small (e.g. dicots such as oaks) genome sizes. Taking advantage
      of the wide range of genome sizes among species, we investigated radiation
      sensitivity which we define in this study as DNA damage (break frequency)
      measured with the alkaline comet assay in isolated nuclei exposed to X-rays. As a
      starting point, we considered two possible explanations for the high radiation
      sensitivity of plants with large genome sizes: (i) inherently higher sensitivity
      of larger genomes and/or (ii) impaired DNA repair. In terms of genome size
      effects, experiments exposing isolated nuclei from six different plant species to
      X-rays, varying in genome sizes from 2.6 to 19.2 Gbp, showed that larger genomes
      are more sensitive to DNA damage by a relationship approximating the cube-root of
      the nuclear volume; e.g. a 10-fold increase in genome size increases sensitivity
      by about 2-fold. With regard to DNA repair, two conifer species, Sawara cypress
      (Chamaecyparis pisifera, 8.9 Gbp genome size) and Scots pine (Pinus sylvestris,
      20 Gbp genome size), both effectively repaired DNA damage within 50 and 70 min,
      respectively, after acute X-ray exposures. Both species also showed delayed
      repair of double-strand DNA breaks, as we previously showed with Arabidopsis
      thaliana and Lolium multiflorum.

PMID- 29045753
TI  - Association Between the rs1229984 Polymorphism in the Alcohol Dehydrogenase 1B
      Gene and Risk for Restless Legs Syndrome.
AB  - Background/Objectives: Several studies have raised the possibility of an
      association between alcohol consumption and the risk of developing restless legs
      syndrome (RLS). Moreover, an important percentage of patients under alcohol
      detoxification therapy develop RLS symptoms that fulfil the criteria for
      idiopathic RLS during alcohol withdrawal. We have aimed to establish the possible
      association between two common single nucleotide polymorphisms (SNPs) in the
      alcohol-dehydrogenase 1B (ADH1B) gene and the risk for RLS. Methods: We studied,
      using specific TaqMan assays, the genotype and allelic variant frequencies of
      ADH1B rs1229984 and ADH1B rs6413413 SNPs in 205 RLS patients and 505 gender
      matched healthy controls. Results: The sum of the frequencies of rs1229984CT and
      rs1229984TT genotypes, as well as the frequency of the rs1229984T allelic
      variant, was significantly higher in RLS patients than in controls, both in the
      whole group and in females. The frequencies of genotypes and allelic variants of
      the rs6413413 SNP were similar between the two groups. RLS patients with the
      rs1229984CT genotype were younger, and those with the rs122984TT genotype older,
      at onset of RLS symptoms than those with the rs1229984CC genotype. None of the
      studied SNPs were related either with positivity of family history for RLS or
      with RLS severity. Conclusions: These results suggest an association between
      rs1229984 SNP and the risk for RLS.

PMID- 29045754
TI  - Genomic Studies of Local Adaptation in Natural Plant Populations.
AB  - Local adaptation arises as a result of selection by the local environment
      favoring phenotypes that enhance fitness. Geographic patterns of phenotypic
      variation are in part due to this selective process. Classically, the genetic
      basis of those phenotypes has been studied in plant populations using a
      quantitative genetic approach in which plants from different source populations
      are grown in common environments, in reciprocal transplant experiments, or in
      studies across a wide geographic and environmentally heterogeneous area.
      Limitations of these approaches to understanding the genetic basis of phenotypic
      variation can now be addressed with next generation sequencing, gene expression
      profiles, and epigenetic analysis. In this paper, I summarize contemporary
      genomic research on local adaptation by comparing findings from the Arabidopsis
      annual plant model system with long-lived tree species in four kinds of local
      adaptation studies: 1) genomic studies of transplant experiments; 2) landscape
      genomic studies; 3) gene expression studies; 4) epigenetic studies of local
      adaptation. Although the basic study designs of common garden, reciprocal
      transplants, and geographic variation have remained constant, the inclusion of
      contemporary genomic approaches has provided substantive advances in our
      understanding of the genetic underpinnings of local adaptation, including the
      impact of climate, the identification of candidate genes involved in genotype-by
      environment interactions, and evidence for the potential role of epigenetic
      modification. Despite these advances, new questions are arising and key areas for
      future research include more exploration of gene networks in response to biotic
      and abiotic stressors and improved statistical tools for traits with polygenic
      inheritance.

PMID- 29045755
TI  - The TriForC database: a comprehensive up-to-date resource of plant triterpene
      biosynthesis.
AB  - Triterpenes constitute a large and important class of plant natural products with
      diverse structures and functions. Their biological roles range from membrane
      structural components over plant hormones to specialized plant defence compounds.
      Furthermore, triterpenes have great potential for a variety of commercial
      applications such as vaccine adjuvants, anti-cancer drugs, food supplements and
      agronomic agents. Their biosynthesis is carried out through complicated, branched
      pathways by multiple enzyme types that include oxidosqualene cyclases, cytochrome
      P450s, and UDP-glycosyltransferases. Given that the number of characterized
      triterpene biosynthesis enzymes has been growing fast recently, the need for a
      database specifically focusing on triterpene enzymology became eminent. Here, we
      present the TriForC database (http://bioinformatics.psb.ugent.be/triforc/),
      encompassing a comprehensive catalogue of triterpene biosynthesis enzymes. This
      highly interlinked database serves as a user-friendly access point to versatile
      data sets of enzyme and compound features, enabling the scanning of a complete
      catalogue of experimentally validated triterpene enzymes, their substrates and
      products, as well as the pathways they constitute in various plant species. The
      database can be accessed by direct browsing or through convenient search tools
      including keyword, BLAST, plant species and substructure options. This database
      will facilitate gene mining and creating genetic toolboxes for triterpene
      synthetic biology.

PMID- 29045756
TI  - Silicon reduces cadmium accumulation by suppressing expression of transporter
      genes involved in cadmium uptake and translocation in rice.
AB  - Silicon (Si) alleviates cadmium (Cd) toxicity and accumulation in a number of
      plant species, but the exact molecular mechanisms responsible for this effect are
      still poorly understood. Here, we investigated the effect of Si on Cd toxicity
      and accumulation in rice (Oryza sativa) by using two mutants (lsi1 and lsi2)
      defective in Si uptake and their wild types (WTs). Root elongation was decreased
      with increasing external Cd concentrations in both WTs and mutants, but Si did
      not show an alleviative effect on Cd toxicity in all lines. By contrast, the Cd
      concentration in both the shoots and roots was decreased by Si in the WTs, but
      not in the mutants. Furthermore, Si supply resulted in a decreased Cd
      concentration in the root cell sap and xylem sap in the WTs, but not in the
      mutants. Pre-treatment with Si also decreased Cd accumulation in the WTs, but not
      in the mutants. Silicon slightly decreased Cd accumulation in the cell wall of
      the roots. The expression level of OsNramp5 and OsHMA2 was down-regulated by Si
      in the WTs, but not in the mutants. These results indicate that the Si-decreased
      Cd accumulation was caused by down-regulating transporter genes involved in Cd
      uptake and translocation in rice.

PMID- 29045757
TI  - Elevated CO2 increases photosynthesis in fluctuating irradiance regardless of
      photosynthetic induction state.
AB  - Leaves are often exposed to fluctuating irradiance, which limits assimilation.
      Elevated CO2 enhances dynamic photosynthesis (i.e. photosynthesis in fluctuating
      irradiance) beyond its effects on steady-state photosynthesis rates. Studying the
      role of CO2 in dynamic photosynthesis is important for understanding plant
      responses to changing atmospheric CO2 partial pressures. The rise of
      photosynthesis after a step-wise increase to 1000 MUmol m-2 s-1, the loss of
      photosynthetic induction after irradiance decreases, and rates of photosynthesis
      during sinusoidal changes in irradiance were studied in tomato (Solanum
      lycopersicum L.) leaves, using three CO2 partial pressures (200, 400, and 800
      ubar). Initial irradiance was set to 0, 50, 100, and 200 MUmol m-2 s-1 to vary
      the initial induction state. Most responses at 200 ubar were not different from
      those at 400 ubar. In contrast, CO2 at 800 ubar increased the relative carbon
      gain by 12% after an increase in irradiance, decreased the loss of photosynthetic
      induction by 14%, and increased dynamic photosynthesis during sine waves by 17%,
      compared with 400 ubar. These effects were additional to steady-state effects of
      elevated CO2 on photosynthesis. The enhancement of dynamic photosynthesis rates
      by elevated CO2 may therefore additionally increase photosynthesis in a future,
      CO2-enriched climate.

PMID- 29045758
TI  - RADON CONCENTRATION TIME SERIES MODELING AND APPLICATION DISCUSSION.
AB  - In the year 2010 a continual radon measurement was established at Mladec Caves in
      the Czech Republic using a continual radon monitor RADIM3A. In order to model
      radon time series in the years 2010-15, the Box-Jenkins Methodology, often used
      in econometrics, was applied. Because of the behavior of radon concentrations
      (RCs), a seasonal integrated, autoregressive moving averages model with exogenous
      variables (SARIMAX) has been chosen to model the measured time series. This model
      uses the time series seasonality, previously acquired values and delayed
      atmospheric parameters, to forecast RC. The developed model for RC time series is
      called regARIMA(5,1,3). Model residuals could be retrospectively compared with
      seismic evidence of local or global earthquakes, which occurred during the RCs
      measurement. This technique enables us to asses if continuously measured RC could
      serve an earthquake precursor.

PMID- 29045759
TI  - The effect of hydroxychloroquine on haemostasis, complement, inflammation and
      angiogenesis in patients with antiphospholipid antibodies.
AB  - Objectives: HCQ has been described as having a beneficial effect in patients with
      APS but its mechanism of action is unclear. We hypothesized that HCQ may have
      effects on subnormal angiogenesis, inflammation and haemostatic biomarkers seen
      in APS. The aim of our study was to assess laboratory markers [annexin A5 (AnxA5)
      anticoagulant activity, tissue factor (TF) levels, thromboelastography (TEG),
      CRP, Bb, C3a and VEGF] in HCQ-naive patients with aPL at baseline and after
      commencing HCQ. Methods: Twenty-two patients with aPL [20 female, 2 male, median
      age 55 (range 18-70) years] had blood taken pre- and 3 months after starting HCQ
      200 mg daily. Results: Soluble TF levels were significantly reduced comparing
      baseline and 3 months after HCQ commencement [401.8 (152.8) vs 300.9 (108) pg/ml
      (P = 0.010)]. No significant changes were found in the following [reported as pre
      and post-HCQ commencement, mean (s.d.)]: AnxA5 anticoagulant ratio [187.1 (29.5)
      vs 193 (31) (P = 0.157)], anti-domain1 beta2 glycoprotein1 IgG activity [1.8 (2)
      vs 1.2 (1.4) MUg/ml (P = 0.105)], complement C3a-des-Arg [147.8 (84.5) vs 154.4
      (88.1) ng/ml (P = 0.905)], complement Bb [1.3 (0.7) vs 1.1 (0.7) MUg/ml (P =
      0.422)], VEGF [68.8 (40) vs 59.4 (19.6) pg/ml (P = 0.454)] and CRP [7 (3.5) vs 7
      (3.9) MUg/ml (P = 0.917)]. TEG results including TEG reaction time, achievement
      of clot firmness, TEG maximum amplitude and TEG percentage lysis 30 and 60 min
      after maximum amplitude showed no significant difference. Conclusion: HCQ
      significantly reduced soluble TF levels in patients with aPL. No significant
      change was observed in AnxA5 activity, anti-domain 1 IgG activity, TEG, CRP,
      complement Bb and C3a-des-Arg, and VEGF. Further studies of a larger patient
      cohort are needed.

PMID- 29045760
TI  - Biological Imaging with Medium-Sensitive Bichromatic Flexible Fluorescent Dyes.
AB  - A family of environment-sensitive shape-shifting molecules have been developed as
      flexible fluorescent (FlexFluor) dyes for biological imaging applications. These
      compounds feature a flexible bithiophene-based fluorophore that gives rise to
      different emission colors in lipophilic or hydrophilic environments, as well as
      side groups that can be synthetically modified with ease. FlexFluor dyes are the
      first fluorescent dyes in which emission color can be used to indicate
      lipid/water environments. The behavior of these dyes in different solvents was
      studied, and used to simultaneously highlight lipid and water contents in adipose
      and brain tissues using optical fluorescence microscopy.

PMID- 29045761
TI  - Reversible Cleavage/Formation of the Chromium-Chromium Quintuple Bond in the
      Highly Regioselective Alkyne Cyclotrimerization.
AB  - Herein we report the employment of the quintuply bonded dichromium amidinates
      [Cr{kappa2 -HC(N-2,6-i Pr2 C6 H3 )(N-2,6-R2 C6 H3 )}]2 (R=iPr (1), Me (7)) as
      catalysts to mediate the [2+2+2] cyclotrimerization of terminal alkynes giving
      1,3,5-trisubstituted benzenes. During the catalysis, the ultrashort Cr-Cr
      quintuple bond underwent reversible cleavage/formation, corroborated by the
      characterization of two inverted arene sandwich dichromium complexes (MU-eta6
      :eta6 -1,3,5-(Me3 Si)3 C6 H3 )[Cr{kappa2 -HC(N-2,6-i Pr2 C6 H3 )(N-2,6-R2 C6 H3
      )}]2 (R=i Pr (5), Me (8)). In the presence of sigma donors, such as THF and 2,4,6
      Me3 C6 H2 CN, the bridging arene 1,3,5-(Me3 Si)3 C6 H3 in 5 and 8 was extruded
      and 1 and 7 were regenerated. Theoretical calculations were employed to disclose
      the reaction pathways of these highly regioselective [2+2+2] cylcotrimerization
      reactions of terminal alkynes.

PMID- 29045763
TI  - Atomic/Molecular Layer Deposition of s-Block Metal Carboxylate Coordination
      Network Thin Films.
AB  - We present novel atomic/molecular layer deposition (ALD/MLD) processes for the
      fabrication of crystalline inorganic-organic coordination network thin films with
      different s-block elements. Terephthalic acid is employed as the organic
      precursor. Such thin films could enable for example, next-generation battery,
      sensor and gas-storage technologies. The deposition processes fulfill the basic
      principles of ALD/MLD-type growth including the sequential self-saturated gas
      surface reactions and atomic/molecular-level control for the film thickness, and
      yield crystalline thin films in a wide deposition temperature range. Structural
      characterization of the films is performed by grazing incidence X-ray diffraction
      (GIXRD) and Fourier-transform infrared (FTIR) spectroscopy. The data do not
      unambiguously prove but also do not rule out the crystal structures previously
      reported for the corresponding bulk samples. We moreover demonstrate the growth
      of crystalline thin films of a new terephthalate material with La as the metal
      component. Upon humidity treatments the Li, Na, K, Ba, and La terephthalate films
      remain unaffected while the Mg, Ca, and Sr terephthalate films reversibly absorb
      water molecules forming well-defined crystalline water-derivative phases.

PMID- 29045762
TI  - Synthesis and Determination of Lipophilicity, Anticonvulsant Activity, and
      Preliminary Safety of 3-Substituted and 3-Unsubstituted N-[(4-Arylpiperazin-1
      yl)alkyl]pyrrolidine-2,5-dione Derivatives.
AB  - A new series of 1,3-substituted pyrrolidine-2,5-dione derivatives as potential
      anticonvulsant agents are described. Initial pharmacological screening of these
      compounds was performed by using acute models of seizures (MES and scPTZ tests)
      in mice after intraperitoneal administration. Quantitative pharmacological
      research revealed that the most promising compounds were N-[{4-(3
      trifluoromethylphenyl)piperazin-1-yl}propyl]-3-benzhydrylpyrrolidine-2,5-dione
      monohydrochloride (11) with a ED50 value of 75.9 mg kg-1 (MES test) and N-[{4
      (3,4-dichlorophenyl)piperazin-1-yl}ethyl]-3-methylpyrrolidine-2,5-dione
      monohydrochloride (18) with ED50 =88.2 mg kg-1 (MES test) and ED50 =65.7 kg mg-1
      (scPTZ test). These compounds displayed a more beneficial protective index than
      well-known antiepileptic drugs. A plausible mechanism of action of compounds 11
      and 18 [molecule 11 blocked the sodium channel (site 2) and 18 blocked both the
      sodium (site 2) and L-type calcium channels] and their preliminary safety in
      vitro were evaluated. Besides, the lipophilicity of all synthesized compounds was
      determined by using UPLC-MS.

PMID- 29045764
TI  - Transuranic Computational Chemistry.
AB  - Recent developments in the chemistry of the transuranic elements are surveyed,
      with particular emphasis on computational contributions. Examples are drawn from
      molecular coordination and organometallic chemistry, and from the study of
      extended solid systems. The role of the metal valence orbitals in covalent
      bonding is a particular focus, especially the consequences of the stabilization
      of the 5f orbitals as the actinide series is traversed. The fledgling chemistry
      of transuranic elements in the +II oxidation state is highlighted. Throughout,
      the symbiotic interplay of experimental and computational studies is emphasized;
      the extraordinary challenges of experimental transuranic chemistry afford
      computational chemistry a particularly valuable role at the frontier of the
      periodic table.

PMID- 29045765
TI  - Oral anti-diabetic agents for women with established diabetes/impaired glucose
      tolerance or previous gestational diabetes planning pregnancy, or pregnant women
      with pre-existing diabetes.
AB  - BACKGROUND: While most guidance recommends the use of insulin in women whose
      pregnancies are affected by pre-existing diabetes, oral anti-diabetic agents may
      be more acceptable to women. The effects of these oral anti-diabetic agents on
      maternal and infant health outcomes need to be established in pregnant women with
      pre-existing diabetes or impaired glucose tolerance, as well as in women with
      previous gestational diabetes mellitus preconceptionally or during a subsequent
      pregnancy. This review is an update of a review that was first published in 2010.
      OBJECTIVES: To investigate the effects of oral anti-diabetic agents in women with
      established diabetes, impaired glucose tolerance or previous gestational diabetes
      who are planning a pregnancy, or pregnant women with pre-existing diabetes, on
      maternal and infant health. The use of oral anti-diabetic agents for the
      management of gestational diabetes in a current pregnancy is evaluated in a
      separate Cochrane Review. SEARCH METHODS: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (31 October 2016) and reference lists of
      retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and
      quasi-RCTs assessing the effects of oral anti-diabetic agents in women with
      established diabetes, impaired glucose tolerance or previous gestational diabetes
      who were planning a pregnancy, or pregnant women with pre-existing diabetes.
      Cluster-RCTs were eligible for inclusion, but none were identified. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed study
      eligibility, extracted data and assessed the risk of bias of the included RCTs.
      Review authors checked the data for accuracy, and assessed the quality of the
      evidence using the GRADE approach. MAIN RESULTS: We identified six RCTs (707
      women), eligible for inclusion in this updated review, however, three RCTs had
      mixed populations (that is, they included pregnant women with gestational
      diabetes) and did not report data separately for the relevant subset of women for
      this review. Therefore we have only included outcome data from three RCTs; data
      were available for 241 women and their infants. The three RCTs all compared an
      oral anti-diabetic agent (metformin) with insulin. The women in the RCTs that
      contributed data had type 2 diabetes diagnosed before or during their pregnancy.
      Overall, the RCTs were judged to be at varying risk of bias. We assessed the
      quality of the evidence for selected important outcomes using GRADE; the evidence
      was low- or very low-quality, due to downgrading because of design limitations
      (risk of bias) and imprecise effect estimates (for many outcomes only one or two
      RCTs contributed data).For our primary outcomes there was no clear difference
      between metformin and insulin groups for pre-eclampsia (risk ratio (RR) 0.63, 95%
      confidence interval (CI) 0.33 to 1.20; RCTs = 2; participants = 227; very low
      quality evidence) although in one RCT women receiving metformin were less likely
      to have pregnancy-induced hypertension (RR 0.58, 95% CI 0.37 to 0.91; RCTs = 1;
      participants = 206; low-quality evidence). Women receiving metformin were less
      likely to have a caesarean section compared with those receiving insulin (RR
      0.73, 95% CI 0.61 to 0.88; RCTs = 3; participants = 241; low-quality evidence).
      In one RCT there was no clear difference between groups for large-for-gestational
      age infants (RR 1.12, 95% CI 0.73 to 1.72; RCTs = 1; participants = 206; very low
      quality evidence). There were no perinatal deaths in two RCTs (very low-quality
      evidence). Neonatal mortality or morbidity composite outcome and
      childhood/adulthood neurosensory disability were not reported.For other secondary
      outcomes we assessed using GRADE, there were no clear differences between
      metformin and insulin groups for induction of labour (RR 1.42, 95% CI 0.62 to
      3.28; RCTs = 2; participants = 35; very low-quality evidence), though infant
      hypoglycaemia was reduced in the metformin group (RR 0.34, 95% CI 0.18 to 0.62;
      RCTs = 3; infants = 241; very low-quality evidence). Perineal trauma, maternal
      postnatal depression and postnatal weight retention, and childhood/adulthood
      adiposity and diabetes were not reported. AUTHORS' CONCLUSIONS: There are
      insufficient RCT data to evaluate the use of oral anti-diabetic agents in women
      with established diabetes, impaired glucose tolerance or previous gestational
      diabetes who are planning a pregnancy, or in pregnant women with pre-existing
      diabetes. Low to very low-quality evidence suggests possible reductions in
      pregnancy-induced hypertension, caesarean section birth and neonatal
      hypoglycaemia with metformin compared with insulin for women with type 2 diabetes
      diagnosed before or during their pregnancy, and no clear differences in pre
      eclampsia, induction of labour and babies that are large-for-gestational age.
      Further high-quality RCTs that compare any combination of oral anti-diabetic
      agent, insulin and dietary and lifestyle advice for these women are needed.
      Future RCTs could be powered to evaluate effects on short- and long-term clinical
      outcomes; such RCTs could attempt to collect and report on the standard outcomes
      suggested in this review. We have identified three ongoing studies and four are
      awaiting classification. We will consider these when this review is updated.

PMID- 29045767
TI  - The oohs and oompahs are in good company!

PMID- 29045766
TI  - Population Pharmacodynamic Analysis of Uric Acid-Lowering Effects of Febuxostat
      Based on Electronic Medical Records in Two Hospitals.
AB  - The aim of this study was to develop a population pharmacodynamic (PPD) model to
      describe uric acid (UA)-lowering effects in patients treated with febuxostat
      based on electronic medical records in 2 independent hospitals (university and
      city hospitals). Interhospital differences in the PPD model were also evaluated.
      We conducted the following 2 approaches to build the PPD models. A PPD model was
      developed separately using individual hospital data, and structural models and
      covariates between the two hospitals were compared (approach A). Another PPD
      model was developed using all available data from both hospitals, and differences
      between the 2 hospitals were evaluated by performing a covariate analysis on all
      PPD parameters (approach B). PPD analyses were performed by NONMEM using data
      from 358 patients. In both approaches, one indirect response model was
      established. In approach A, 2 diuretics (loops and thiazides) and renal function
      tests (Scr or BUN) were selected as covariates for the UA baseline level (serum
      UA levels just before the febuxostat treatment), whereas 2 diuretics and BUN were
      selected in approach B. A covariate analysis indicated that loops and thiazides
      increased UA baseline levels by 7%-14% and 6%-11%, respectively. In approach B,
      "hospital" was identified as a significant covariate for the UA baseline level;
      the baseline level was 7% higher in the city hospital. A PPD analysis may provide
      a precise description of the time course of the UA-lowering effects of febuxostat
      and quantitatively detect an interhospital difference in the UA baseline level.

PMID- 29045768
TI  - A Brief History of Lithium Treatment in Psychiatry.
AB  - The history of lithium as a psychiatric medication is marked by its serendipitous
      discovery, its lengthy path to US Food and Drug Administration approval, and
      controversy surrounding its current status in bipolar disorder treatment. Without
      doubt, the discovery of lithium as a psychotropic agent forever changed the
      course of psychiatry. The drug's fascinating, and sometimes contentious, history
      is reviewed here.

PMID- 29045769
TI  - Placebo Effects in the Treatment of Noncognitive Symptoms of Alzheimer's Disease:
      Analysis of the CATIE-AD Data.
AB  - OBJECTIVE: To compare symptom trajectories between placebo and active drug
      responders and to examine whether early placebo improvement would be associated
      with subsequent placebo response in the treatment of patients with behavioral and
      psychological symptoms of dementia. METHODS: A post hoc analysis of data from 371
      patients with DSM-IV Alzheimer's disease in Phase 1 of the Clinical Antipsychotic
      Trials of Intervention Effectiveness for Alzheimer's disease (CATIE-AD) (April
      2001 to November 2004) was conducted. Patients were randomly assigned to double
      blind treatment with olanzapine, quetiapine, risperidone, or placebo.
      Trajectories of change in Brief Psychiatric Rating Scale (BPRS) total scores were
      compared between placebo and active drug responders. The predictive power of
      improvement at week 2 for response at week 8 was investigated, and sensitivity
      and specificity of incremental 5% cutoff points between 5% and 25% reduction in
      BPRS total score at week 2 were calculated. RESULTS: There were no significant
      differences in symptom trajectories between placebo and active drug responders.
      BPRS score reduction at week 2 was significantly associated with placebo response
      at week 8 (odds ratio = 1.13; P < .001). Use of a cutoff of 10% showed the
      highest accuracy of 0.67 (sensitivity, 0.63; specificity, 0.70). CONCLUSIONS:
      Symptom trajectories of improvement of behavioral and psychological symptoms of
      dementia follow the same pattern irrespective of treatment. A 10% improvement at
      week 2 was the most appropriate predictor of subsequent placebo response at week
      8, which may indicate utility for the placebo lead-in phase to minimize future
      trial failures of treatment for noncognitive symptoms of Alzheimer's disease.
      TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00015548.

PMID- 29045770
TI  - Treatment to Enhance Cognition in Bipolar Disorder (TREC-BD): Efficacy of a
      Randomized Controlled Trial of Cognitive Remediation Versus Active Control.
AB  - OBJECTIVE: Cognitive dysfunction is a core symptom dimension in bipolar disorder
      and a strong predictor of functional outcomes. Cognitive remediation (CR)
      produces moderate, durable effects on cognition in patients with schizophrenia;
      however, studies of CR in patients with bipolar disorder are sparse and findings
      have been mixed. Thus, the aim of this study was to evaluate the effects of CR
      versus active control in patients with bipolar disorder with psychosis. METHODS:
      Patients with a DSM-IV diagnosis of bipolar disorder with psychosis (n = 75) were
      randomized to a 70-hour computerized CR program or a dose-matched computer
      control using a parallel design with 1:1 allocation between July 2011 and
      November 2015. Cognition (primary outcome) and clinical and community functioning
      (secondary outcomes) were assessed at baseline, at treatment midpoint (after 20
      25 hours of training), posttreatment, and at durability (after 6 months of no
      study contact). Participants and assessment staff were blind to group membership.
      RESULTS: 75 participants were randomly assigned to a treatment group, and 72
      participants initiated the active phase of treatment and were included in the
      primary, intent-to-treat analysis (CR: n = 39; Control: n = 33). Linear mixed
      effects models examining the effects of CR versus Control at posttreatment showed
      medium to large effects of CR on processing speed (d = 0.42), visual learning and
      memory (d = 0.92), and the composite (d = 0.80). Superiority of CR over Control
      on processing speed (d = 0.65) and composite (d = 0.83) was maintained or
      increased at durability. CR was not associated with change in community
      functioning, although cognitive change was associated with functional change
      across the sample. CONCLUSIONS: Cognitive remediation produced significant
      improvements over an active control in several cognitive domains and the
      cognitive composite. While both groups improved on several domains relative to
      baseline, durability of gains was unique to CR. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01470781.

PMID- 29045771
TI  - National Trends in and Correlates of Nonmedical Use of Prescription Stimulants,
      Nonmedical Use Frequency, and Use Disorders.
AB  - OBJECTIVE: To examine national trends in and correlates of nonmedical use of
      prescription stimulants, nonmedical use frequency, and use disorders among
      individuals aged 12-64 years. METHODS: Data from 783,400 persons aged 12-64 who
      participated in the 2003-2014 National Surveys on Drug Use and Health (NSDUH).
      Descriptive analyses and bivariable and multivariable logistic regression and
      zero-truncated negative binomial regression models were applied. RESULTS: Our
      multivariable results show that among individuals aged 12-64, the national
      prevalence of nonmedical use of prescription stimulants in 2003-2004 was higher
      than in 2007-2008 and was similar to that in 2009-2011, but was lower than in
      2013-2014. Among those who used prescription stimulants nonmedically, the
      frequency of nonmedical use of prescription stimulants in 2003-2004 was lower
      than that in 2005-2006 and was similar to that in 2007-2014, and the prevalence
      of prescription stimulant use disorders in 2003-2004 was higher than that in 2005
      2010, but was similar to that in 2011-2014. Among nonmedical prescription
      stimulant users aged 12-64 in 2013-2014, 53.2% reported that their source of
      stimulants used nonmedically last time was from relatives/friends for free. Our
      study also identified correlates of prescription stimulant nonmedical use, use
      frequency, and use disorders. Co-occurring substance use disorders are common
      among those with prescription stimulant nonmedical use problems. CONCLUSIONS:
      Among individuals aged 12-64 in the United States, after adjusting for
      covariates, the prevalence of nonmedical use of prescription stimulants in 2013
      2014 was higher than that in 2003-2004. The results of this study help inform and
      target efforts to reduce prescription stimulant nonmedical use, use frequency,
      and use disorders.

PMID- 29045772
TI  - Current Preventive Strategies for Preovulatory Progesterone Elevation During
      Ovarian Stimulation for In Vitro Fertilization
AB  - The purpose of this review is to present contemporary measures for preventing
      theincrease in preovulatory progesterone (P) and its adverse effects on ovarian
      stimulation in in vitrofertilization (IVF). For the last 20 years, the increase
      of preovulatory P has been a topic of numerousdiscussions because its role is not
      fully understood in terms of its impact on pregnancy outcome afterIVF. Some
      studies failed to establish a connection between the preovulatory P increase and
      successfulIVF outcome regardless of the level of P, while, conversely, most other
      studies have reported on adverseeffects of elevated P concentrations. Current
      strategies to prevent the increase in preovulatory P includean individualized
      approach with the use of mild stimulation protocols and early application ofhuman
      chorionic gonadotropin for ovulation induction among good responders, delay in
      the transferof fresh embryos from 3rd to 5th day, and cryopreservation of all
      embryos with the thawed embryotransfer in the natural cycle. Nevertheless,
      further studies are needed to confirm the current preventivemethods or enable the
      application of new strategies in order to lower or eliminate the
      detrimentaleffects of preovulatory P rise during ovarian stimulation in IVF.

PMID- 29045773
TI  - Oral Lesions in Kidney Transplant Recipients
AB  - Permanent immunosuppression is necessary to prevent rejection after
      kidneytransplantation. However, it may predispose patients to different
      conditions and diseases includingoral lesions. The most common benign oral
      lesions in kidney transplant recipients are gingival hyperplasia,oral
      candidiasis, hairy leukoplakia and saburral tongue. Oral form of Kaposi sarcoma,
      althoughrarely, can also be seen in kidney transplant patients. In this review,
      we present the incidence, etiology,clinical findings, diagnosis and treatment
      options for these lesions. For kidney transplant recipients,itis important to
      maintain good oral hygiene and care, as well as regular professional control by
      thedentist. This approach can reduce the number and severity of oral lesions.

PMID- 29045774
TI  - Effect of Inhalational Anesthetics on Acute Kidney Injury
AB  - Acute kidney injury (AKI) is a serious complication associated with
      increasedmorbidity and mortality. Total incidence of AKI in hospitalized patients
      is 1%-5%. As many as 30%of these patients develop AKI in the perioperative
      period, which is associated with anesthesia andsurgery. Despite scientific
      advances and improved surgery techniques, as well as treatment in intensivecare
      units, no significant decrease in AKI incidence has been achieved. To change this
      outcome, it isimportant to identify patients at risk of AKI and prevent its
      occurrence. Correct selection of anestheticdrugs during general anesthesia,
      adjusted to the individual needs of patients, also influences theoverall outcome
      of treatment. Nowadays, inhalational anesthetics are not considered nephrotoxic.
      Themore so, inhalational anesthetics have a strong and direct protective effect
      on many organs throughpreconditioning and postconditioning. New studies have
      shown that sevoflurane diminishes ischemia/reperfusion kidney injury and has an
      anti-inflammatory effect, thus having the potential to reduce theoccurrence of
      AKI. Given the incidence of AKI in the perioperative period, as well as new
      findingsabout anesthetics, the issue of anesthetic selection during general
      anesthesia might be of crucial importancefor the final outcome of treatment.

PMID- 29045775
TI  - The Impact of Sleep Deprivation on the Brain
AB  - Each sleep phase is characterized by specific chemical, cellular and anatomic
      eventsof vital importance for normal neural functioning. Different forms of sleep
      deprivation may lead to adecline of cognitive functions in individuals. Studies
      in this field make a distinction between total sleepdeprivation, chronic sleep
      restriction, and the situation of sleep disruption. Investigations covering
      theacute effects of sleep deprivation on the brain show that the discovered
      behavioral deficits in most casesregenerate after two nights of complete sleep.
      However, some studies done on mice emphasize thepossible chronic effects of long
      term sleep deprivation or chronic restriction on the occurrence of
      neurodegenerativediseases such as Alzheimer's disease and dementia. In order to
      better understand the acuteand chronic effects of sleep loss, the mechanisms of
      neural adaptation in the situations of insufficientsleep need to be further
      investigated. Future integrative research on the impact of sleep deprivation
      onneural functioning measured through the macro level of cognitive functions and
      the micro molecular andcell level could contribute to more accurate conclusions
      about the basic cellular mechanisms responsiblefor the detected behavioral
      deficits occurring due to sleep deprivation.

PMID- 29045776
TI  - Surgical Treatment of Metastatic Disease of the Vertebral Column
AB  - Spinal metastatic disease is a rather common occurrence and definitely
      warrantsattention and treatment due to the high likelihood of leaving cancer
      patients severely disabled in theirfinal months of life. Recent developments in
      the understanding of the behavior of different tumortypes, as well as advances in
      surgical treatment, are allowing for the evolution of treatment
      algorithms,especially when surgical treatment is to be considered. This paper
      gives an overview of the decision-makingprocess and the array of surgical options
      currently available.

PMID- 29045778
TI  - A Honeycomb-like Co@N-C Composite for Ultrahigh Sulfur Loading Li-S Batteries.
AB  - Because of the high theoretical capacity of 1675 mAh g-1 and high energy density
      of 2600 Wh kg-1, respectively, lithium-sulfur batteries are attracting intense
      interest. However, it remains an enormous challenge to realize high utilizations
      and loadings of sulfur in cathodes for the practical applications of Li-S
      batteries. Herein, we design a quasi-2D Co@N-C composite with honeycomb
      architecture as a multifunctional sulfur host via a simple sacrificial templates
      method. The cellular flake with large surface area and honeycomb architecture can
      encapsulate much more sulfur, leading to high sulfur content (HSC) composites,
      and by stacking these HSC flakes, a high sulfur loading (HSL) electrode can be
      realized due to their high layer bulk density. Compared to our previous work in
      multifunctional Co-N-C composites, the cellular Co@N-C composite displays a
      distinct enhancement in the sulfur content, sulfur loading, cycle stability, and
      rate performance. Benefiting from the cellular morphology, a composite with an
      HSC of 93.6 wt % and an electrode with an HSL of 7.5 mg cm-2 can be obtained
      simultaneously, which exhibited excellent rate performance up to 10 C (3.6 mg cm
      2) and great cycling stability.

PMID- 29045777
TI  - Prevalence of Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in
      Population of North-West Croatia Aged 40 and Over
AB  - The purpose of this study was to assess the prevalence of pseudoexfoliation
      syndromeand pseudoexfoliation glaucoma and to evaluate its association with open
      angle glaucoma inpatients attending the Department of Ophthalmology, Dr Tomislav
      Bardek General Hospital in Koprivnica,northwestern Croatia. This prospective
      study was conducted at Dr Tomislav Bardek GeneralHospital between December 2012
      and October 2013. A total of 5349 subjects aged 40 or abovepresenting for general
      ophthalmic examination were screened for pseudoexfoliation syndrome
      andpseudoexfoliation glaucoma. Each patient underwent complete ophthalmologic
      examination includingocular history, visual acuity testing, slit-lamp
      examination, applanation tonometry, optic disc evaluation,visual field analysis,
      and gonioscopy if glaucoma was suspected. Exclusion criteria were
      pseudophakicand/or aphakic patients of any age, patients with concomitant
      congenital eye disease, andpatients with very dense ocular media opacities. Out
      of 5349 patients examined, there were 1994(38.38%) males and 3201 (61.61%)
      females. The prevalence of pseudoexfoliation syndrome was 3.6%and primary open
      angle glaucoma 9.4%, out of which 23.6% with pseudoexfoliation glaucoma.
      Thefindings of this study improve our knowledge of pseudoexfoliation syndrome and
      pseudoexfoliationglaucoma in Croatia, particularly in the northwest region.

PMID- 29045779
TI  - Hierarchically Porous Graphitic Carbon with Simultaneously High Surface Area and
      Colossal Pore Volume Engineered via Ice Templating.
AB  - Developing hierarchical porous carbon (HPC) materials with competing textural
      characteristics such as surface area and pore volume in one material is difficult
      to accomplish, particularly for an atomically ordered graphitic carbon. Herein we
      describe a synthesis strategy to engineer tunable HPC materials across micro-,
      meso-, and macroporous length scales, allowing the fabrication of a graphitic HPC
      material (HPC-G) with both very high surface area (>2500 m2/g) and pore volume
      (>11 cm3/g), the combination of which has not been attained previously. The
      mesopore volume alone for these materials is up to 7.53 cm3/g, the highest ever
      reported, higher than even any porous carbon's total pore volume, which for our
      HPC-G material was >11 cm3/g. This HPC-G material was explored for use both as a
      supercapacitor electrode and for oil adsorption, two applications that require
      either high surface area or large pore volume, textural properties that are
      typically exclusive to one another. We accomplished these high textural
      characteristics by employing ice templating not only as a route for macroporous
      formation but as a synergistic vehicle that enabled the significant loading of
      the mesoporous hard template. This design scheme for HPC-G materials can be
      utilized in broad applications, including electrochemical systems such as
      batteries and supercapacitors, sorbents, and catalyst supports, particularly
      supports where a high degree of thermal stability is required.

PMID- 29045780
TI  - Mechanisms of Activation and Subunit Release in Ca2+/Calmodulin-Dependent Protein
      Kinase II.
AB  - Calcium/calmodulin-dependent protein kinase II is an enzyme involved in many
      different functions, including the so-called long-term potentiation, a mechanism
      that strengthens synapses in a persistent mode and is believed to be a basic
      cellular mechanism for memory formation. Here we study the conformational changes
      of the enzyme due to phosphorylation of some key residues that are believed to
      drive the transition from an inhibited to an active state; it is this active
      state the one associated with long-term potentiation. We found that the
      conformational changes could be explained in terms of three charged regions in
      the three main subdomains of the enzyme: the hub, linker, and kinase. The role of
      phosphorylation is to change the charge relation between them, turning on and off
      their interactions and switching between an attractive state (nonphosphorylated
      or inhibited) and a not attractive one (phosphorylated or active). We also show
      that phosphorylated subunits become less stable, and this could favor their
      release from the multimer, as has been already observed experimentally.

PMID- 29045781
TI  - Development of Clickable Monophosphoryl Lipid A Derivatives toward Semisynthetic
      Conjugates with Tumor-Associated Carbohydrate Antigens.
AB  - A semisynthetic strategy to obtain monophosphoryl lipid A derivatives equipped
      with clickable (azide, alkyne, double bond, or thiol precursor) moieties,
      starting from the native lipid A isolated from Escherichia coli, is presented.
      These lipid A derivatives can be conjugated with other interesting biomolecules,
      such as tumor-associated carbohydrate antigens (TACAs). In this way, the
      immunostimulant activity of monophosphoryl lipid A can significantly improve the
      immunogenicity of TACAs, thus opening access to potential self-adjuvant
      anticancer vaccine candidates. A monophosphoryl lipid A-Thomson-Friedenreich (TF)
      antigen conjugate was obtained to demonstrate the feasibility of this
      methodology, which stands as a valuable, rapid, and scalable alternative to the
      highly complex approaches of total synthesis recently reported to the same aim. A
      preliminary evaluation of the immunological activity of this conjugate as well as
      of other semisynthetic lipid A derivatives was also reported.

PMID- 29045782
TI  - Noncovalent Protein Arginine Deiminase (PAD) Inhibitors Are Efficacious in Animal
      Models of Multiple Sclerosis.
AB  - Peptidyl arginine deiminases have been shown to be hyperactive in
      neurodegenerative diseases including multiple sclerosis. An alpha-amino acid
      based core structure, derived from a hydantoin core, with unique heterocycles on
      the side chains were synthesized as potential noncovalent inhibitors of PAD
      enzymes. Among the various heterocycles investigated, compound 23, carrying an
      imidazole moiety, exhibited the highest potency in this series with some
      selectivity for PAD2, and was further investigated in vivo. Pharmacokinetics in
      mice suggested the Cmax to be 12.0 +/- 2.5 MUg/mL and 170 +/- 10 ng/mL in the
      serum and brain, respectively, when compound 23 was administered at 50 mg/kg via
      single dose ip. At the same dose, compound 23 also reversed physical disability
      and cleared the brain of T-cell infiltration in an EAE mouse model of multiple
      sclerosis (MS). This novel series of compounds show promise for further
      development as disease modifying agents for the potential treatment of MS.

PMID- 29045783
TI  - Reinvestigation of the Substitutions Reaction of Stereogenic Phosphoryl
      Compounds: Stereochemistry, Mechanism, and Applications.
AB  - Nucleophilic substitutions at P centers are of high importance in biological
      processes and asymmetric synthesis. However, detailed studies on this topic are
      rare. P-Stereogenic compounds containing P-Cl, P-O, and P-S bonds were
      diastereoselectively prepared and then used to study the substitution of Cl, O,
      and S at phosphorus centers with organometallic reagents. It was proposed that
      with alkynyl metallic reagents an SN2-like mechanism (route A1) and a Berry
      pseudorotation (BPR) of pentacoordinated phosphorus intermediates (route B1) were
      involved and afforded P-inverted and P-retained products, respectively. The P
      inverted conversion of a P-Cl functionality to a P-C functionality can be
      controlled by either the temperature or the order of addition of the starting
      materials. The introduction of a P-Cl bond using an alkyl metallic reagent
      proceeded through routes A2 and A2'. At higher temperatures, P-inverted products
      were predominantly afforded via SN2-like route A2. At lower temperatures, bis
      substituted products were formed via route A2' and cleavage of the P-O bond. The
      P-S bonds were accompanied by the epimerization of the starting materials,
      triggered by the alkylthio anion, via route C. The epimerization can be
      suppressed by the use of a poorly soluble magnesium alkylthiolate, and the P
      retained compounds will be formed as the major products via route B3 and BPR of
      the intermediates.

PMID- 29045785
TI  - Programming Enzyme-Initiated Autonomous DNAzyme Nanodevices in Living Cells.
AB  - Molecular nanodevices are computational assemblers that switch defined states
      upon external stimulation. However, interfacing artificial nanodevices with
      natural molecular machineries in living cells remains a great challenge. Here, we
      delineate a generic method for programming assembly of enzyme-initiated DNAzyme
      nanodevices (DzNanos). Two programs including split assembly of two partzymes and
      toehold exchange displacement assembly of one intact DNAzyme initiated by
      telomerase are computed. The intact one obtains higher assembly yield and
      catalytic performance ascribed to proper conformation folding and active
      misplaced assembly. By employing MnO2 nanosheets as both DNA carriers and source
      of Mn2+ as DNAzyme cofactor, we find that this DzNano is well assembled via a
      series of conformational states in living cells and operates autonomously with
      sustained cleavage activity. Other enzymes can also induce corresponding DzNano
      assembly with defined programming modules. These DzNanos not only can monitor
      enzyme catalysis in situ but also will enable the implementation of cellular
      stages, behaviors, and pathways for basic science, diagnostic, and therapeutic
      applications as genetic circuits.

PMID- 29045784
TI  - Metal Dependence of the Xylose Isomerase from Piromyces sp. E2 Explored by
      Activity Profiling and Protein Crystallography.
AB  - Xylose isomerase from Piromyces sp. E2 (PirXI) can be used to equip Saccharomyces
      cerevisiae with the capacity to ferment xylose to ethanol. The biochemical
      properties and structure of the enzyme have not been described even though its
      metal content, catalytic parameters, and expression level are critical for rapid
      xylose utilization. We have isolated the enzyme after high-level expression in
      Escherichia coli, analyzed the metal dependence of its catalytic properties, and
      determined 12 crystal structures in the presence of different metals, substrates,
      and substrate analogues. The activity assays revealed that various bivalent
      metals can activate PirXI for xylose isomerization. Among these metals, Mn2+ is
      the most favorable for catalytic activity. Furthermore, the enzyme shows the
      highest affinity for Mn2+, which was established by measuring the activation
      constants (Kact) for different metals. Metal analysis of the purified enzyme
      showed that in vivo the enzyme binds a mixture of metals that is determined by
      metal availability as well as affinity, indicating that the native metal
      composition can influence activity. The crystal structures show the presence of
      an active site similar to that of other xylose isomerases, with a d-xylose
      binding site containing two tryptophans and a catalytic histidine, as well as two
      metal binding sites that are formed by carboxylate groups of conserved aspartates
      and glutamates. The binding positions and conformations of the metal-coordinating
      residues varied slightly for different metals, which is hypothesized to
      contribute to the observed metal dependence of the isomerase activity.

PMID- 29045786
TI  - Combining Accuracy and Efficiency: An Incremental Focal-Point Method Based on
      Pair Natural Orbitals.
AB  - In this work, we present a new pair natural orbitals (PNO)-based incremental
      scheme to calculate CCSD(T) and CCSD(T0) reaction, interaction, and binding
      energies. We perform an extensive analysis, which shows small incremental errors
      similar to previous non-PNO calculations. Furthermore, slight PNO errors are
      obtained by using TPNO = TTNO with appropriate values of 10-7 to 10-8 for
      reactions and 10-8 for interaction or binding energies. The combination with the
      efficient MP2 focal-point approach yields chemical accuracy relative to the
      complete basis-set (CBS) limit. In this method, small basis sets (cc-pVDZ, def2
      TZVP) for the CCSD(T) part are sufficient in case of reactions or interactions,
      while some larger ones (e.g., (aug)-cc-pVTZ) are necessary for molecular
      clusters. For these larger basis sets, we show the very high efficiency of our
      scheme. We obtain not only tremendous decreases of the wall times (i.e., factors
      >102) due to the parallelization of the increment calculations as well as of the
      total times due to the application of PNOs (i.e., compared to the normal
      incremental scheme) but also smaller total times with respect to the standard PNO
      method. That way, our new method features a perfect applicability by combining an
      excellent accuracy with a very high efficiency as well as the accessibility to
      larger systems due to the separation of the full computation into several small
      increments.

PMID- 29045787
TI  - Mechanistic Origin of the Combined Effect of Surfaces and Mechanical Agitation on
      Amyloid Formation.
AB  - Interactions between proteins and surfaces in combination with hydrodynamic flow
      and mechanical agitation can often trigger the conversion of soluble peptides and
      proteins into aggregates, including amyloid fibrils. Despite the extensive
      literature on the empirical effects of surfaces and mechanical forces on the
      formation of amyloids, the molecular details of the mechanisms underlying this
      behavior are still elusive. This limitation is, in part, due to the complex
      reaction network underlying the formation of amyloids, where several microscopic
      reactions of nucleation and growth can occur both at the interfaces and in bulk.
      In this work, we design a high-throughput assay based on nanoparticles and we
      apply a chemical kinetic platform to analyze the mechanisms underlying the effect
      of surfaces and mechanical forces on the formation of amyloid fibrils from human
      insulin under physiological conditions. By considering a variety of polymeric
      nanoparticles with different surface properties we explore a broad range of
      repulsive and attractive interactions between insulin and surfaces. Our analysis
      shows that hydrophobic interfaces induce the formation of amyloid fibrils by
      specifically promoting the primary heterogeneous nucleation rate. In contrast,
      mechanical forces accelerate the formation of amyloid fibrils by favoring mass
      transport and further amplify the number of fibrils by promoting fragmentation
      events. Thus, surfaces and agitation have a combined effect on the kinetics of
      protein aggregation observed at the macroscopic level but, individually, they
      each affect distinct microscopic reaction steps: the presence of interfaces
      generates primary nucleation events of fibril formation, which is then amplified
      by mechanical forces. These results suggest that the inhibition of surface
      induced heterogeneous nucleation should be considered a primary target to
      suppress aggregation and explain why in many systems the simultaneous presence of
      surfaces and hydrodynamic flow enhances protein aggregation.

PMID- 29045788
TI  - Importance of Surface IrOx in Stabilizing RuO2 for Oxygen Evolution.
AB  - The high precious metal loading and high overpotential of the oxygen evolution
      reaction (OER) prevents the widespread utilization of polymer electrolyte
      membrane (PEM) water electrolyzers. Herein we explore the OER activity and
      stability in acidic electrolyte of a combined IrOx/RuO2 system consisting of RuO2
      thin films with submonolayer (1, 2, and 4 A) amounts of IrOx deposited on top.
      Operando extended X-ray absorption fine structure (EXAFS) on the Ir L-3 edge
      revealed a rutile type IrO2 structure with some Ir sites occupied by Ru, IrOx
      being at the surface of the RuO2 thin film. We monitor corrosion on IrOx/RuO2
      thin films by combining electrochemical quartz crystal microbalance (EQCM) with
      inductively coupled mass spectrometry (ICP-MS). We elucidate the importance of
      submonolayer surface IrOx in minimizing Ru dissolution. Our work shows that we
      can tune the surface properties of active OER catalysts, such as RuO2, aiming to
      achieve higher electrocatalytic stability in PEM electrolyzers.

PMID- 29045789
TI  - Nano-Hydroxyapatite Stimulation of Gene Expression Requires Fgf Receptor,
      Phosphate Transporter, and Erk1/2 Signaling.
AB  - Hydroxyapatite (HAp) is critical to health both as the main structural material
      of the skeleton and storage material of calcium and phosphate. Nanosized HAp
      (nHAp) is naturally produced by mineralizing cells during bone formation and
      remodeling and is the main constituent of the skeleton. As such, HAp is currently
      being investigated as a therapeutic biomaterial for orthopedic and dental
      purposes. Recent studies have suggested that extracellular nHAp can influence
      osteoblast lineage commitment and cell function through changes in gene
      expression; however, the mechanisms remain to be elucidated. Here, the cellular
      and molecular mechanism by which rod-shaped nHAp (10 * 100 nm) stimulates gene
      expression in preosteoblast bone marrow stromal cells was investigated. Electron
      microscopy detected a rapid and stable interaction of nHAp with the cell
      membrane, which correlated with a strong stimulation of the Erk1/2 signaling
      pathway. Results also identified the requirement of the Fgf receptor signaling
      and phosphate-transporters for nHAp regulated gene expression whereas a calcium
      sensing receptor inhibitor had no effect. Collectively, the study uncovers novel
      signaling pathways and cellular events specifically stimulated by and required
      for the cellular response to free extracellular HAp. The results provide insight
      into the osteoblastic response to HAp relevant to functional mineralization and
      pathological calcification and could be used in the development of biomaterials
      for orthopedic purposes.

PMID- 29045790
TI  - Three-Step Synthesis of Chiral Spirocyclic Oxaphospholenes.
AB  - Chiral spirocylic oxaphospholenes were prepared in a three-step sequence from
      chiral pool terpenoid ketones. After addition of a metal acetylide, the resulting
      propargyl alcohols were converted stereoselectively into their allenylphosphonate
      counterparts. In the last step, they were conveniently cyclized into
      spirooxaphospholenes with one equivalent of iodine without purification. When
      starting from sterically hindered terpenes, allenylphosphonates were also easily
      obtained but showed to be unreactive or rearranged under these cyclization
      conditions.

PMID- 29045791
TI  - Efficient and High-Color-Purity Light-Emitting Diodes Based on In Situ Grown
      Films of CsPbX3 (X = Br, I) Nanoplates with Controlled Thicknesses.
AB  - We report a facile solution-based approach to the in situ growth of perovskite
      films consisting of monolayers of CsPbBr3 nanoplates passivated by bulky
      phenylbutylammonium (PBA) cations, that is, two-dimensional layered
      PBA2(CsPbBr3)n-1PbBr4 perovskites. Optimizing film formation processes leads to
      layered perovskites with controlled n values in the range of 12-16. The layered
      perovskite emitters show quantum-confined band gap energies with a narrow
      distribution, suggesting the formation of thickness-controlled quantum-well
      (TCQW) structures. The TCQW CsPbBr3 films exhibit smooth surface features, narrow
      emission line widths, low trap densities, and high room-temperature
      photoluminance quantum yields, resulting in high-color-purity green light
      emitting diodes (LEDs) with remarkably high external quantum efficiencies (EQEs)
      of up to 10.4%. The solution-based approach is extended to the preparation of
      TCQW CsPbI3 films for high-color-purity red perovskite LEDs with high EQEs of up
      to 7.3%.

PMID- 29045792
TI  - Glycopeptides as Targets for Dendritic Cells: Exploring MUC1 Glycopeptides
      Binding Profile toward Macrophage Galactose-Type Lectin (MGL) Orthologs.
AB  - The macrophage galactose-type lectin (MGL) recognizes glycan moieties exposed by
      pathogens and malignant cells. Particularly, mucin-1 (MUC1) glycoprotein presents
      an altered glycosylation in several cancers. To estimate the ability of distinct
      MGL orthologs to recognize aberrant glycan cores in mucins, we applied evanescent
      field detection to a versatile MUC1-like glycopeptide microarray platform. Here,
      as binding was sequence-dependent, we demonstrated that not only sugars but also
      peptide region impact the recognition of murine MGL1 (mMGL1). In addition, we
      observed for all three MGL orthologs that divalent glycan presentation increased
      the binding. To assess the utility of the glycopeptide binders of the MGL
      orthologs for MGL targeting, we performed uptake assays with fluorescein-MUC1
      using murine dendritic cells. A diglycosylated MUC1 peptide was preferentially
      internalized in an MGL-dependent fashion, thus showing the utility for divalent
      MGL targeting. These findings may be relevant to a rational design of antitumor
      vaccines targeting dendritic cells via MGL.

PMID- 29045793
TI  - Adsorption Removal of Glycidyl Esters from Palm Oil and Oil Model Solution by
      Using Acid-Washed Oil Palm Wood-Based Activated Carbon: Kinetic and Mechanism
      Study.
AB  - Acid-washed oil palm wood-based activated carbon (OPAC) has been investigated for
      its potential application as a promising adsorbent in the removal of glycidyl
      esters (GEs) from both palm oil and oil model (hexadecane) solution. It was
      observed that the removal rate of GEs in palm oil was up to >95%, which was
      significantly higher than other adsorbents used in this study. In batch
      adsorption system, the adsorption efficiency and performance of acid-washed OPAC
      were evaluated as a function of several experimental parameters such as contact
      time, initial glycidyl palmitate (PGE) concentration, adsorbent dose, and
      temperature. The Langmuir, Freundlich, and Dubinin-Radushkevich models were used
      to describe the adsorption equilibrium isotherm, and the equilibrium data were
      fitted best by the Langmuir model. The maximum adsorption capacity of acid-washed
      OPAC was found to be 36.23 mg/g by using the Langmuir model. The thermodynamic
      analysis indicated that the adsorption of PGE on acid-washed OPAC was an
      endothermic and physical process in nature. The experimental data were fitted by
      using pseudo-first-order, pseudo-second-order, and intraparticle diffusion
      models. It was found that the kinetic of PGE adsorption onto acid-washed OPAC
      followed well the pseudo-second-order model for various initial PGE
      concentrations and the adsorption process was controlled by both film diffusion
      and intraparticle diffusion. The desorption test indicated the removal of GEs
      from palm oil was attributed to not only the adsorption of GEs on acid-washed
      OPAC, but also the degradation of GEs adsorbed at activated sites with acidic
      character. Furthermore, no significant difference between before and after PGE
      adsorption in oil quality was observed.

PMID- 29045795
TI  - TBHP/TBAI-Mediated Oxidative Cascade Reaction Consisting of Dimerization,
      Cyclization, and 1,2-Aryl Migration: Metal-Free Synthesis of Pyrrolin-4-ones and
      Highly Substituted Pyrroles.
AB  - Treatment of enamino esters with TBHP (t-butylhydroperoxide) and TBAI (t
      butylammonium iodide) in HFIP (hexafluoroisopropanol) was found to afford a
      variety of substituted pyrrolin-4-one compounds. This metal-free oxidative
      cascade reaction consists of the key steps of coupling of two radical
      intermediates, an intramolecular ring closure, and an exclusive 1,2-aryl radical
      migration. Upon treatment with a base, the obtained pyrrolin-4-ones could be
      converted to the highly substituted pyrrole compounds.

PMID- 29045794
TI  - Allosteric Modulation of the Faecalibacterium prausnitzii Hepatitis Delta Virus
      like Ribozyme by Glucosamine 6-Phosphate: The Substrate of the Adjacent Gene
      Product.
AB  - Self-cleaving ribozymes were discovered 30 years ago and have been found
      throughout nature, from bacteria to animals, but little is known about their
      biological functions and regulation, particularly how cofactors and metabolites
      alter their activity. A hepatitis delta virus-like self-cleaving ribozyme maps
      upstream of a phosphoglucosamine mutase (glmM) open reading frame in the genome
      of the human gut bacterium Faecalibacterium prausnitzii. The presence of a
      ribozyme in the untranslated region of glmM suggests a regulation mechanism of
      gene expression. In the bacterial hexosamine biosynthesis pathway, the enzyme
      glmM catalyzes the isomerization of glucosamine 6-phosphate into glucosamine 1
      phosphate. In this study, we investigated the effect of these metabolites on the
      co-transcriptional self-cleavage rate of the ribozyme. Our results suggest that
      glucosamine 6-phosphate, but not glucosamine 1-phosphate, is an allosteric ligand
      that increases the self-cleavage rate of drz-Fpra-1, providing the first known
      example of allosteric modulation of a self-cleaving ribozyme by the substrate of
      the adjacent gene product. Given that the ribozyme is activated by the glmM
      substrate, but not the product, this allosteric modulation may represent a
      potential feed-forward mechanism of gene expression regulation in bacteria.

PMID- 29045796
TI  - The modification of the ketogenic diet mitigates its stunting effects in rodents.
AB  - The high-fat and low-carbohydrate ketogenic diet (HFKD) is extensively studied
      within the fields of numerous diseases, including cancer and neurological
      disorders. Since most studies incorporate animal models, ensuring the quality of
      ketogenic rodent diets is important, both in the context of laboratory animal
      welfare as well as for the accuracy of the obtained results. In this study we
      implemented a modification to a commonly used ketogenic rodent chow by replacing
      non-resorbable cellulose with wheat bran. We assessed the effects of month-long
      treatment with either the unmodified or the modified HFKD on the growth and
      development of young male rats. Daily body weight, functional performance, and
      brain morphometric parameters were assessed to evaluate the influence of both
      applied diets on rodent development. Our results revealed that the unmodified
      ketogenic chow induced strong side effects that included weakness, emaciation,
      and brain undergrowth concomitant to growth inhibition. However, application of
      the ketogenic chow supplemented with wheat bran suppressed these adverse side
      effects, which was associated with the restoration of insulin-like growth factor
      1 and a decrease in corticosterone levels. We have also shown that the
      advantageous results of the modified HFKD are not species- or sex-specific. Our
      data indicate that the proposed HFKD modification even allows for its application
      in young animals, without causing detrimental side effects.

PMID- 29045797
TI  - Public Health Detailing to Increase Routine HIV Screening in Baltimore, Maryland:
      Satisfaction, Feasibility, and Effectiveness.
AB  - The objective of this study was to evaluate the satisfaction with, and the
      feasibility and effectiveness of, a public health detailing project focused on
      increasing routine human immunodeficiency virus (HIV) screening of people aged 13
      64 by primary care providers working in areas of Baltimore City, Maryland, with
      high rates of HIV transmission (defined as a mean geometric viral load of >=1500
      copies/mL per census tract). In public health detailing, trained public health
      professionals (ie, detailers) visit medical practice sites to meet with providers
      and site staff members, with the intention of influencing changes in clinical
      practice policy and/or behavior. During 2014, detailers made personal visits and
      gave HIV Testing Action Kits containing maps, educational and guideline
      documents, and resource lists to 166 providers and office managers at 85 primary
      care sites. At follow-up, 88 of 91 (96.7%) providers and 37 of 38 (97.4%) clinic
      managers were very satisfied or satisfied with the project. Of the 79 sites
      eligible at follow-up (ie, those that had not closed or merged with another
      practice), 76 (96.2%) had accepted at least 1 HIV Testing Action Kit, and 67 of
      90 (74.4%) providers had increased their HIV screening. Public health detailing
      projects can be used to educate and support providers, establish relationships
      between providers and local health departments, and disseminate public health
      messages.

PMID- 29045798
TI  - Effects of reclamation years on composition and diversity of soil bacterial
      communities in Northwest China.
AB  - The objective of this study was to evaluate bacterial community structure and
      diversity in soil aggregate fractions when salinized farmland was reclaimed after
      >27 years of abandonment and then farmed again for 1, 5, 10, and 15 years.
      Illumina MiSeq high-throughput sequencing was performed to characterize the soil
      bacterial communities in 5 aggregate size classes in each treatment. The results
      indicated that reclamation significantly increased macro-aggregation (>0.25 mm),
      as well as soil organic C, available N, and available P. The 10-year field had
      the largest proportion (93.9%) of soil in the macro-aggregate size classes (i.e.,
      >0.25 mm) and the highest soil electrical conductivity. The 5 most dominant phyla
      in the soil samples were Proteobacteria, Actinobacteria, Gemmatimonadetes,
      Acidobacteria, and Bacteroidetes. The phylogenetic diversity, Chao1, and Shannon
      indices increased after the abandoned land was reclaimed for farming, reaching
      maximums in the 15-year field. Among aggregate size classes, the 1-0.25 mm
      aggregates generally had the highest phylogenetic diversity, Chao1, and Shannon
      indices. Soil organic C and soil electrical conductivity were the main
      environmental factors affecting the soil bacterial communities. The composition
      and structure of the bacterial communities also varied significantly depending on
      soil aggregate size and time since reclamation.

PMID- 29045799
TI  - Opt-out HIV and Hepatitis C Testing at the Dallas County Jail: Uptake,
      Prevalence, and Demographic Characteristics of Testers.
AB  - Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection are
      common in the criminal justice system. We offered opt-out HIV/HCV testing at the
      Dallas County Jail during intake from June 2015 to November 2016, after which
      testing was integrated into routine phlebotomy processes. The uptake of testing
      increased from 12.9% (118/915) in June 2015 to 80.5% (269/334) in January 2016.
      HIV was confirmed in 1.0% (30/3155) of inmates; 6 were new diagnoses and all were
      linked to care. HCV antibody positivity was found in 16.4% (500/4042) of inmates.
      Sixty percent (155/258) of HCV-positive inmates born between 1945 and 1965 (ie,
      baby boomers) were non-Hispanic black, whereas 56.2% (136/242) born after 1965
      were non-Hispanic white. Testing only baby boomers would have missed
      approximately half of HCV infections, predominantly among young, non-Hispanic
      white people. Future efforts should expand HIV and HCV testing in jails, as it is
      feasible, acceptable, and increases prevention and engagement in care for a high
      prevalence, hard-to-reach population.

PMID- 29045800
TI  - Survival and Complications of Single Dental Implants in the Edentulous Mandible
      Following Immediate or Delayed Loading: A Randomized Controlled Clinical Trial.
AB  - It was the aim of this 24-mo randomized controlled clinical trial to investigate
      whether the survival of a single median implant placed in the edentulous mandible
      to retain a complete denture is not compromised by immediate loading. Secondary
      outcomes were differences in prosthetic complications between the loading
      principles. Each of the 158 patients who received an implant was randomly
      assigned to the immediate loading group ( n = 81) or the delayed loading group (
      n = 77). Recall visits were performed 1 mo after implant placement (for only the
      delayed loading group) and 1, 4, 12, and 24 mo after implant loading. Nine
      implants failed in the immediate loading group, all within the first 3 mo of
      implant loading, and 1 implant failed in the delayed loading group prior to
      loading. Noninferiority of implant survival of the immediate loading group, as
      compared with the delayed loading group, could not be shown ( P = 0.81).
      Consistent with this result, a secondary analysis with Fisher exact test revealed
      that the observed difference in implant survival between the treatment groups was
      indeed statistically significant ( P = 0.019). The most frequent prosthetic
      complications and maintenance interventions in the mandible were retention
      adjustments, denture fractures, pressure sores, and matrix exchanges. There was
      only 1 statistically significant difference between the groups regarding the
      parameter "fracture of the denture base in the ball attachment area" ( P =
      0.007). The results indicate that immediate loading of a single implant in the
      edentulous mandible reveals inferior survival than that of delayed loading and
      therefore should be considered only in exceptional cases (German Clinical Trials
      Register: DRKS00003730).

PMID- 29045801
TI  - Plant-growth-promoting rhizobacteria Bacillus subtilis RR4 isolated from rice
      rhizosphere induces malic acid biosynthesis in rice roots.
AB  - Malic acid (MA), one of the major organic acid exudates from roots, plays a
      significant role in the chemotaxis of beneficial bacteria to the plant's
      rhizosphere. In this study, the effect of a plant-growth-promoting
      rhizobacterium, Bacillus subtilis RR4, on the synthesis and exudation of MA from
      roots is demonstrated in rice. To test the chemotactic ability of strain RR4
      towards MA, a capillary chemotaxis assay was performed, which revealed a positive
      response (relative chemotactic ratio of 6.15 with 10 MUmol/L MA); with increasing
      concentrations of MA, an elevated chemotactic response was observed. Quantitative
      polymerase chain reaction, performed to analyze the influence of RR4 on the MA
      biosynthetic gene, malate synthase (OsMS), and the transporter gene, aluminium
      activated malate transporter (OsALMT), demonstrated significant differential
      expression, with 1.8- and -0.58-fold changes, respectively, in RR4-treated roots.
      The gene expression pattern of OsMS corroborated the data obtained by high
      performance liquid chromatography, which showed elevated MA levels in roots (1.52
      fold), whereas the levels of MA in root exudates were not altered significantly
      although expression of OsALMT was reduced. Our results demonstrate that B.
      subtilis RR4 is chemotactic to MA and can induce biosynthesis of MA in rice
      roots.

PMID- 29045802
TI  - Using Medicare Prices - Toward Equity and Affordability in the ACA Marketplace.

PMID- 29045803
TI  - Chitosan-Based Trilayer Scaffold for Multitissue Periodontal Regeneration.
AB  - Periodontal regeneration is still a challenge for periodontists and tissue
      engineers, as it requires the simultaneous restoration of different tissues
      namely, cementum, gingiva, bone, and periodontal ligament (PDL). Here, we
      synthetized a chitosan (CH)-based trilayer porous scaffold to achieve periodontal
      regeneration driven by multitissue simultaneous healing. We produced 2 porous
      compartments for bone and gingiva regeneration by cross-linking with genipin
      either medium molecular weight (MMW) or low molecular weight (LMW) CH and freeze
      drying the resulting scaffolds. We synthetized a third compartment for PDL
      regeneration by CH electrochemical deposition; this allowed us to produce highly
      oriented microchannels of about 450-um diameter intended to drive PDL fiber
      growth toward the dental root. In vitro characterization showed rapid equilibrium
      water content for MMW-CH and LMW-CH compartments (equilibrium water content after
      5 min >85%). The MMW-CH compartment degraded more slowly and provided
      significantly more resistance to compression (28% +/- 1% of weight loss at 4 wk;
      compression modulus HA = 18 +/- 6 kPa) than the LMW-CH compartment (34% +/- 1%;
      7.7 +/- 0.8 kPa) as required to match the physiologic healing rates of bone and
      gingiva and their mechanical properties. More than 90% of all human primary
      periodontal cell populations tested on the corresponding compartment survived
      during cytocompatibility tests, showing active cell metabolism in the alkaline
      phosphatase and collagen deposition assays. In vivo tests showed high
      biocompatibility in wild-type mice, tissue ingrowth, and vascularization within
      the scaffold. Using the periodontal ectopic model in nude mice, we preseeded
      scaffold compartments with human gingival fibroblasts, osteoblasts, and PDL
      fibroblasts and found a dense mineralized matrix within the MMW-CH region, with
      weakly mineralized deposits at the dentin interface. Together, these results
      support this resorbable trilayer scaffold as a promising candidate for
      periodontal regeneration.

PMID- 29045805
TI  - Triclocarban enhances short-chain fatty acids production from anaerobic
      fermentation of waste activated sludge.
AB  - Triclocarban (TCC), one typical antibacterial agent being widely used in various
      applications, was found to be present in waste activated sludge at significant
      levels. To date, however, its effect on anaerobic fermentation of sludge has not
      been investigated. This work therefore aims to fill this knowledge gap.
      Experimental results showed that when TCC content in sludge increased from 26.7
      +/- 5.3 to 520.5 +/- 12.6 mg per kilogram total suspended solids, the maximum
      concentration of short-chain fatty acids (SCFA) increased from 32.6 +/- 2.5 to
      228.2 +/- 3.6 (without pH control) and from 211.7 +/- 2.4 to 378.3 +/- 3.2 mg
      COD/g VSS (initial pH 10), respectively. The large promotion of acetic acid was
      found to be the major reason for the enhancement of total SCFA production.
      Although a significant level of TCC was degraded in the fermentation process,
      SCFA was neither produced from TCC nor affected by its major intermediates at the
      relevant levels. It was found that TCC facilitated solubilization, acidogenesis,
      acetogenesis, and homoacetogenesis processes but inhibited methanogenesis
      process. Microbial analysis revealed that the increase of TCC increased the
      microbial community diversity, the abundances of SCFA (especially acetic acid)
      producers, and the activities of key enzymes relevant to acetic acid production.

PMID- 29045807
TI  - Evidence reversal-when new evidence contradicts current claims: a systematic
      overview review of definitions and terms.
AB  - OBJECTIVE: To explore the terminology and definitions surrounding the phenomenon
      of evidence reversal (ER)-which occurs when an existing claim is tested and the
      original evidence is contradicted by new and stronger evidence. STUDY DESIGN AND
      SETTING: For this systematic overview review, multiple medical and gray
      literature databases were systematically searched from inception to 2016 as well
      as hand searches of relevant journals, websites, blogs, article bibliographies,
      citing articles, and related articles. All reviews directly and indirectly
      defining ER were included and rated for quality using AMSTAR. RESULTS: A total of
      87 articles met the inclusion criteria. Fifty unique sets of terms related to ER
      were identified: nine described the phenomenon of reversal; 17 described the
      consequences of reversal; 20 described targets; four described potential
      predictors of reversal. CONCLUSION: ER has only recently become a topic of formal
      exploration. There are many terms that relate to the concept of reversal, which
      fall into the categories of phenomenon, consequences, targets, and potential
      predictors of reversal. Consensus should be reached on which terms are most
      appropriate such that subject headings can be developed and cohesion can be
      brought to this emerging field of meta-research. (PROSPERO Registration number:
      CRD42014013768).

PMID- 29045804
TI  - Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic
      leukemia (T-ALL) cells.
AB  - Matrine, a natural product extracted from the root of Sophora flavescens, is a
      promising alternative drug in different types of cancer. Here, we aimed to
      investigate the therapeutic effects and underlying molecular mechanisms of
      matrine on human acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Cell
      viability and IC50 values were determined by WST-1 cell cytotoxicity assay. Cell
      cycle distribution and apoptosis rates were analyzed by flow cytometry.
      Expression patterns of 44 selected miRNAs and 44 RNAs were analyzed by
      quantitative reverse transcription polymerase chain reaction (qRT-PCR) using the
      Applied Biosystems 7500 Fast Real-Time PCR System. Matrine inhibited cell
      viability and induced apoptosis of CCRF-CEM cells in a dose-dependent manner.
      Cell cycle analysis demonstrated that matrine-treated CCRF-CEM cells
      significantly accumulated in the G0/G1 phase compared with the untreated control
      cells. hsa-miR-376b-3p (-37.09 fold, p = 0.008) and hsa-miR-106b-3p (-16.67 fold,
      p = 0.028) expressions were decreased, whereas IL6 (95.47 fold, p = 0.000011) and
      CDKN1A (140.03 fold, p = 0.000159) expressions were increased after matrine
      treatment. Our results suggest that the downregulation of hsa-miR-106b-3p leads
      to the upregulation of target p21 gene, CDKN1A, and plays a critical role in the
      cell cycle progression by arresting matrine-treated cells in the G0/G1 phase.

PMID- 29045806
TI  - Safety of magnetic resonance imaging in patients with legacy pacemakers and
      defibrillators and abandoned leads.
AB  - BACKGROUND: During magnetic resonance imaging (MRI), abandoned leads may act as
      antennae that result in tissue heating and arrhythmia induction. OBJECTIVE: The
      purpose of this study was to assess the safety of MRI in patients with abandoned
      leads, with the addition of cardiac troponin T (cTnT) assessment to screen for
      myocardial damage. METHODS: We reviewed our prospectively collected database of
      patients with cardiovascular implantable electronic devices (CIEDs) undergoing
      MRI between 2008 and 2017 at Mayo Clinic, Rochester, MN, and selected patients
      who had abandoned leads. We compared the adverse events in this population with
      an age, sex, and site of MRI-matched cohort of patients selected from this
      database. We evaluated paired (before/after) cTnT values using MRI in these
      patients. RESULTS: Of 952 patients, 80 (8.4%) underwent 97 MRI scans with CIEDs
      in situ with 90 abandoned leads in place during the scans. The median age was 66
      years (interquartile range 22.3 years) 66.1 years (interquartile range, Q1,Q3:
      53.6, 75.9) with 66.3% (53 patients) men. There was no clinical or electrical
      evidence of CIED dysfunction, arrhythmias, or pain. Paired samples for the
      measurement of cTnT values were available in 40 patients undergoing 44 MRI
      examinations. The mean difference between the pre- and postimaging values was 
      0.002 +/- 0.006 ng/mL (interquartile range 0). There was no difference after
      adjustment for total number of leads per patient and total number of implantable
      cardioverter-defibrillator coils. CONCLUSION: There was no evidence of myocardial
      injury as measured by paired cTnT. The risk of MRI with abandoned leads appears
      low, suggesting a favorable risk-benefit profile in patients with CIEDs and
      abandoned leads who are considered for MRI.

PMID- 29045808
TI  - Kaplan-Meier survival analysis overestimates cumulative incidence of health
      related events in competing risk settings: a meta-analysis.
AB  - OBJECTIVES: Kaplan-Meier survival analysis overestimates cumulative incidence in
      competing risks (CRs) settings. The extent of overestimation (or its clinical
      significance) has been questioned, and CRs methods are infrequently used. This
      meta-analysis compares the Kaplan-Meier method to the cumulative incidence
      function (CIF), a CRs method. STUDY DESIGN AND SETTING: We searched MEDLINE,
      EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies
      for studies estimating cumulative incidence using the Kaplan-Meier method and
      CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs)
      comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random
      effects models. We performed stratified meta-analyses by clinical area, rate of
      CRs (CRs/events of interest), and follow-up time. RESULTS: Of 2,192 identified
      abstracts, we included 77 studies in the systematic review and meta-analyzed 55.
      The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence
      interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest
      among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies
      related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and
      gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. CONCLUSION: The Kaplan-Meier method
      overestimated the cumulative incidence across 10 clinical areas. Using CRs
      methods will ensure accurate results inform clinical and policy decisions.

PMID- 29045809
TI  - Postnatal Sonic hedgehog (Shh) responsive cells give rise to oligodendrocyte
      lineage cells during myelination and in adulthood contribute to remyelination.
AB  - Sonic hedgehog (Shh) regulates a wave of oligodendrocyte production for extensive
      myelination during postnatal development. During this postnatal period of
      oligodendrogenesis, we fate-labeled cells exhibiting active Shh signaling to
      examine their contribution to the regenerative response during remyelination.
      Bitransgenic mouse lines were generated for induced genetic fate-labeling of
      cells actively transcribing Shh or Gli1. Gli1 transcription is an effective
      readout for canonical Shh signaling. ShhCreERT2 mice and Gli1CreERT2 mice were
      crossed to either R26tdTomato mice to label cells with red fluorescence, or,
      R26IAP mice to label membranes with alkaline phosphatase. When tamoxifen (TMX)
      was given on postnatal days 6-9 (P6-9), Shh ligand synthesis was prevalent in
      neurons of ShhCreERT2; R26tdTomato mice and ShhCreERT2;R26IAP mice. In
      Gli1CreERT2 crosses, TMX from P6-9 detected Gli1 transcription in cells that
      populated the corpus callosum (CC) during postnatal myelination. Delaying TMX to
      P14-17, after the peak of oligodendrogenesis, significantly reduced labeling of
      Shh synthesizing neurons and Gli1 expressing cells in the CC. Importantly,
      Gli1CreERT2;R26tdTomato mice given TMX from P6-9 showed Gli1 fate-labeled cells
      in the adult (P56) CC, including cycling progenitor cells identified by EdU
      incorporation and NG2 immunolabeling. Furthermore, after cuprizone demyelination
      of the adult CC, Gli1 fate-labeled cells incorporated EdU and were immunolabeled
      by NG2 early during remyelination while forming myelin-like membranes after
      longer periods for remyelination to progress. These studies reveal a postnatal
      cell population with transient Shh signaling that contributes to
      oligodendrogenesis during CC myelination, and gives rise to cells that continue
      to proliferate in adulthood and contribute to CC remyelination.

PMID- 29045810
TI  - A novel next generation sequencing assay as an alternative to currently available
      methods for hepatitis C virus genotyping.
AB  - Chronic HCV infection is one of the leading causes of liver-related death and in
      many countries it is a primary reason for having a liver transplant. HCV genotype
      identification has long been used in the clinical practice, since different
      genotypes have different response rates and required different doses and
      durations of IFN/RBV treatment; moreover both the frequency and the pattern of
      resistance to different Direct-Acting Antivirals (DAAs) classes are subtype
      specific. Hence the necessity to make an accurate HCV subtyping becomes a
      fundamental tool to optimize current and future clinical management of HCV
      infected subjects. In the present study the performance of a next generation
      sequencing (NGS: based on the Ion Torrent Platform-Vela Sentosa SQ 301 sequencer)
      HCV genotyping assay has been evaluated. The current method targets a region of
      the NS5B gene and it is the unique NGS based market CE-IVD assay. As a
      comparative method a commercial method based on the detection via reverse
      hybridization of 5'UTR and core regions (Versant HCV Genotype 2.0 Assay, LiPA,
      Siemens) was selected. A total 207 plasma samples from HCV infected individuals
      were used. No selection was made for these samples that were submitted for
      routine HCV genotyping. The results show Vela NGS assay assigns major number of
      HCV subtypes with respect LiPA. Concerning genotype 1 and 3, the discrepancy of
      assigned subtypes for LiPA with respect to Vela NGS assay is not relevant (1.8%
      and 2%, respectively); in contrast, the difference of assigned subtypes for
      genotypes 2 and 4 is very high (96.6% and 100%, respectively). The resistance
      mutations data, except for 1a and 1b subtypes, remain scarce; the future relevant
      challenge will be to identify subtypes-specific drug resistance mutations, which
      are essential to create highly personalized therapeutic pathways.

PMID- 29045811
TI  - TOP2A induces malignant character of pancreatic cancer through activating beta
      catenin signaling pathway.
AB  - It has been reported that Topoisomerase II alpha (TOP2A) could induce tumor
      development and progression in many cancer types. Herein, through analysis of
      different independent cohorts, we found TOP2A was up-regulated in pancreatic
      cancer as compared with non-tumor tissues. Moreover, the up-regulation of TOP2A
      was significantly correlated with tumor metastasis and shorter survival in
      patients with pancreatic cancer. Knockdown of TOP2A in pancreatic cancer cell
      lines inhibited cell proliferation and migration. Furthermore, bioinformatics
      analysis revealed TOP2A activatesbeta-catenin pathway in pancreatic cancer.
      Mechanistically, we demonstrated TOP2A acts as a co-activator ofbeta-catenin and
      activates EMT process. Further investigation showed TOP2A was a direct target of
      mir-139, which was validated by dual-luciferase reporter gene assay. The effects
      of mir-139 on pancreatic cancer were also mechanistically, functionally and
      clinically investigated. Taken together, our research identified a novel miR
      139?TOP2A?beta-catenin axis driving the malignant progression of pancreatic
      cancer.

PMID- 29045812
TI  - Facial emotion perception in patients with epilepsy: A systematic review with
      meta-analysis.
AB  - Facial emotion perception is a fundamental social competency relying on a
      specialised, yet distributed, neural network. This review aimed to determine
      whether patients with epilepsy have facial emotion perception accuracy
      impairments overall, or for a subset of emotions (anger, disgust, happiness,
      sadness, fear, and surprise), and the relationship to epilepsy type,
      demographic/treatment variables, and brain organisation. Database searches used
      PRISMA guidelines with strict inclusion/exclusion criteria. Thirty included
      studies assessed patients with temporal lobe (TLE; n=709), frontocentral (FCE;
      n=22), and genetic generalised (GGE; n=48) epilepsy. Large deficits emerged in
      patients with epilepsy compared to controls (n=746; Hedges' g=0.908-1.076).
      Patients with TLE were significantly impaired on all emotions except surprise;
      patients with GGE were significantly impaired in anger, disgust, and fear
      perception. Meta-regression of patients with TLE revealed younger age at testing
      was associated with lower accuracy. This review provides evidence for marked
      global deficits of emotion perception in epilepsy, with differential emotion
      specific impairment patterns in patients with TLE and GGE.

PMID- 29045813
TI  - Antimicrobial resistance, virulence genes and genetic relatedness of Salmonella
      enterica serotype Enteritidis isolates recovered from human gastroenteritis in
      Tehran, Iran.
AB  - OBJECTIVES: Salmonella enterica serotype Enteritidis is a major serotype
      associated with human salmonellosis. The main objective of this study was to
      determine the antibiotic susceptibility patterns and the presence of virulence
      associated genes among S. Enteritidis strains isolated from patients with
      gastroenteritis in Tehran, Iran. METHODS: Over a period of 14 months (May 2015 to
      July 2016), 44 S. Enteritidis isolates recovered from clinical sources were
      characterised for antimicrobial susceptibility and virulence genes. Possible
      genetic relatedness among the strains was also assessed using pulsed-field gel
      electrophoresis (PFGE). RESULTS: Salmonella Enteritidis isolates showed high
      rates of resistance to ciprofloxacin (90.9%) and nalidixic acid (77.3%). Of the
      44 S. Enteritidis isolates, 30 (68.2%) were resistant to three or more
      antibiotics. Twenty-two different antimicrobial resistance patterns were detected
      among the isolates. The most frequent resistance type was antibiotype 14
      (resistance to ciprofloxacin, cefuroxime and nalidixic acid), occurring in 8
      (18.2%) of the isolates. Notably, all of the isolates carried invA, sefA, sipA
      and sopE2 virulence genes. Furthermore, 17 virulence profiles were observed among
      the strains. The most common virulence profile was VP1 (n=17; 38.6%), harbouring
      all of the virulence genes. Two distinct PFGE patterns were observed among 44S.
      Enteritidis isolates. There was no association between virulence profiles or
      antibiotypes and PFGE clusters. CONCLUSIONS: Overall, this study provides
      valuable information on the virulence gene content, antibiotic resistance and
      genetic diversity of S. Enteritidis isolated from human sources in Iran.

PMID- 29045814
TI  - Role of KCC2-dependent potassium efflux in 4-Aminopyridine-induced Epileptiform
      synchronization.
AB  - A balance between excitation and inhibition is necessary to maintain stable brain
      network dynamics. Traditionally, seizure activity is believed to arise from the
      breakdown of this delicate balance in favor of excitation with loss of
      inhibition. Surprisingly, recent experimental evidence suggests that this
      conventional view may be limited, and that inhibition plays a prominent role in
      the development of epileptiform synchronization. Here, we explored the role of
      the KCC2 co-transporter in the onset of inhibitory network-induced seizures. Our
      experiments in acute mouse brain slices, of either sex, revealed that optogenetic
      stimulation of either parvalbumin- or somatostatin-expressing interneurons
      induced ictal discharges in rodent entorhinal cortex during 4-aminopyridine
      application. These data point to a proconvulsive role of GABAA receptor signaling
      that is independent of the inhibitory input location (i.e., dendritic vs.
      somatic). We developed a biophysically realistic network model implementing
      dynamics of ion concentrations to explore the mechanisms leading to inhibitory
      network-induced seizures. In agreement with experimental results, we found that
      stimulation of the inhibitory interneurons induced seizure-like activity in a
      network with reduced potassium A-current. Our model predicts that interneuron
      stimulation triggered an increase of interneuron firing, which was accompanied by
      an increase in the intracellular chloride concentration and a subsequent KCC2
      dependent gradual accumulation of the extracellular potassium promoting
      epileptiform ictal activity. When the KCC2 activity was reduced, stimulation of
      the interneurons was no longer able to induce ictal events. Overall, our study
      provides evidence for a proconvulsive role of GABAA receptor signaling that
      depends on the involvement of the KCC2 co-transporter.

PMID- 29045816
TI  - Assessment of bacterial membrane fluidity by flow cytometry.
AB  - It can be interesting to evaluate the cytoplasmic membrane fluidity of bacteria
      in order to understand the impacts of stresses during processing. Traditionally,
      membrane fluidity was assessed by fluorescence anisotropy measured by
      spectrofluorimetry, but this method does not make it possible to reveal the
      heterogeneity of bacterial populations. Flow cytometry, as opposed to
      spectrofluorimetry, has the ability to simultaneously detect different sub
      populations. We developed a new method to measure the fluorescence anisotropy of
      bacterial membranes using flow cytometry. This technique, coupled with
      viability/mortality/fluidity co-staining, now allows us to assess the membrane
      fluidity of viable, damaged and dead cells. Then, we show that membrane of viable
      bacterial cells becomes more and more rigid during batch culture, culminating in
      the death of the cells. This new flow cytometric method therefore opens new
      perspectives to study changes and adaptations in bacterial membranes of viable
      cells depending on the micro-environment during fermentation or stress
      applications.

PMID- 29045815
TI  - Eosinophils and eosinophil-associated diseases: An update.
AB  - The goal of this series is to offer a survey of the latest literature for
      clinicians and scientists alike, providing a list of important recent advances
      relevant to the broad field of allergy and immunology. This particular assignment
      was to cover the topic of eosinophils. In an attempt to highlight major ideas,
      themes, trends, and advances relevant to basic and clinical aspects of eosinophil
      biology, a search of articles published since 2015 in the Journal of Allergy and
      Clinical Immunology and other high-impact journals was performed. Articles were
      then reviewed and organized, and then key findings were summarized. Given space
      limitations, many outstanding articles could not be included, but the hope is
      that what follows provides a succinct overview of recently published work that
      has significantly added to our knowledge of eosinophils and eosinophil-associated
      diseases.

PMID- 29045817
TI  - Transcriptomic Characterization of the Human Cell Cycle in Individual
      Unsynchronized Cells.
AB  - The highly fine-tuned dynamics of cell cycle gene expression have been intensely
      studied for several decades. However, some previous observations may be difficult
      to fully decouple from artifacts induced by traditional cell synchronization
      procedures. In addition, bulk cell measurements may have disguised intricate
      details. Here, we address this by sorting and transcriptomic sequencing of single
      cells progressing through the cell cycle without prior synchronization. Genes and
      pathways with known cell cycle roles are confirmed, associated regulatory
      sequence motifs are determined, and we also establish ties between other
      biological processes and the unsynchronized cell cycle. Importantly, we find the
      G1 phase to be surprisingly heterogeneous, with transcriptionally distinct early
      and late time points. We additionally note that mRNAs accumulate to reach maximum
      total levels at mitosis and find that stable transcripts show reduced cell-to
      cell variability, consistent with the transcriptional burst model of gene
      expression. Our study provides the first detailed transcriptional profiling of an
      unsynchronized human cell cycle.

PMID- 29045818
TI  - Conformational Plasticity of Hepatitis C Virus Core Protein Enables RNA-Induced
      Formation of Nucleocapsid-like Particles.
AB  - Many of the unanswered questions associated with hepatitis C virus assembly are
      related to the core protein (HCVcp), which forms an oligomeric nucleocapsid
      encompassing the viral genome. The structural properties of HCVcp have been
      difficult to quantify, at least in part because it is an intrinsically disordered
      protein. We have used single-molecule Forster Resonance Energy Transfer
      techniques to study the conformational dimensions and dynamics of the HCVcp
      nucleocapsid domain (HCVncd) at various stages during the RNA-induced formation
      of nucleocapsid-like particles. Our results indicate that HCVncd is a typical
      intrinsically disordered protein. When it forms small ribonucleoprotein complexes
      with various RNA hairpins from the 3' end of the HCV genome, it compacts but
      remains intrinsically disordered and conformationally dynamic. Above a critical
      RNA concentration, these ribonucleoprotein complexes rapidly and cooperatively
      assemble into large nucleocapsid-like particles, wherein the individual HCVncd
      subunits become substantially more extended.

PMID- 29045819
TI  - Disruption of the Epidermal Barrier Induces Regulatory T Cells via IL-33 in Mice.
AB  - Disturbance of the epidermal barrier by UVR is associated with the release of
      antimicrobial peptides and inflammatory cytokines for the purpose of a danger
      response. On the other hand, UVR causes immunosuppression via regulatory T cells
      (Treg) that limit the inflammatory reaction. The concurrent induction of
      antimicrobial peptides and Treg by UVR may represent a counter-regulatory
      mechanism in response to barrier disruption, preventing microbial superinfection
      and sensitization to contact allergens, respectively, both of which cross
      impaired epidermis more easily. Thus, using a model of murine contact
      hypersensitivity we examined if disruption of the epidermal barrier only
      initiates similar counter-regulatory mechanisms via the generation of Treg.
      Sensitization through tape-stripped skin induced a weaker contact
      hypersensitivity response than in control mice. This was due to the induction of
      antigen-specific Treg, as demonstrated in adoptive transfer and depletion
      experiments utilizing DEREG mice. Treg induction by tape stripping was linked to
      the expression of the alarmin IL-33, as blockade of IL-33 exacerbated contact
      hypersensitivity, whereas injection of IL-33 inhibited contact hypersensitivity
      and induced Treg. These results demonstrate that epidermal barrier disruption, in
      addition to danger signals, induces regulatory events that prevent exaggerated
      skin inflammation and that IL-33 appears to be critically involved in this
      process.

PMID- 29045820
TI  - Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of
      Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients
      with Superficial Basal Cell Carcinoma.
AB  - For the treatment of superficial basal cell carcinoma, a prospective,
      noninferiority, randomized controlled multicenter trial with 601 patients showed
      that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to
      methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after
      treatment. No definite conclusion could be drawn regarding the superiority of
      imiquimod over 5-fluorouracil. We now present the 5-year follow-up results
      according to the intention-to-treat analysis. Five years after treatment, the
      probability of tumor-free survival was 62.7% for methyl aminolevulinate
      photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for
      imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9
      76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil
      were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P =
      0.09), respectively, when compared with methyl aminolevulinate photodynamic
      therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65
      (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results
      of this trial show that 5% imiquimod cream is superior to both methyl
      aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of
      efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod
      cream as the first choice for noninvasive treatment in most primary superficial
      basal cell carcinomas.

PMID- 29045821
TI  - MiR-93-5p promotes gastric cancer-cell progression via inactivation of the Hippo
      signaling pathway.
AB  - MiR-93-5p has been previously found to be associated with gastric cancer (GC)
      tumorigenesis; however, the current understanding of its function in this context
      remains largely incomplete. In the present study, we showed that miR-93-5p was
      upregulated in GC tissues. We also demonstrated that miR-93-5p overexpression
      promoted the proliferation, migration, invasion, and chemoresistance of SGC-7901
      cells in vitro, and conversely, that endogenously silencing miR-93-5p expression
      induced the opposite effects in HGC-27 cells. Overexpression of miR-93-5p was
      found to inactivate the Hippo pathway, and furthermore, miR-93-5p knockdown
      activated Hippo signaling. MiR-93-5p upregulation was also shown to inhibit the
      expression of two well-characterized Hippo pathway regulators, protocadherin Fat
      4 (FAT4), and large tumor suppressors 2 (LATS2), at both the mRNA and protein
      level. Additionally, the results of bioinformatics analyses and luciferase
      reporter assays indicated that miR-93-5p directly targets the 3'-UTR of FAT4 and
      LATS2. Taken together, these results demonstrate that miR-93-5p promotes GC-cell
      progression via the inactivation of the Hippo signaling pathway, and thus,
      represents a potential therapeutic target for the treatment of GC.

PMID- 29045822
TI  - Individual effects of the copia and gypsy enhancer and insulator on chromatin
      marks, eRNA synthesis, and binding of insulator proteins in transfected genetic
      constructs.
AB  - Enhancers and insulators are involved in the regulation of gene expression, but
      the basic underlying mechanisms of action of these elements are unknown. We
      analyzed the individual effects of the enhancer and the insulator from Drosophila
      mobile elements copia [enh(copia)] and gypsy using transfected genetic constructs
      in S2 cells. This system excludes the influence of genomic cis regulatory
      elements. The enhancer-induced synthesis of 350-1050-nt-long enhancer RNAs
      (eRNAs) and H3K4me3 and H3K18ac marks, mainly in the region located about 300bp
      downstream of the enhancer. Insertion of the insulator between the enhancer and
      the promoter reduced these effects. We also observed the binding of dCTCF to the
      enhancer and to gypsy insulator. Our data indicate that a single gypsy insulator
      interacts with both the enhancer and the promoter, while two copies of the gypsy
      insulator preferentially interact with each other. Our results suggest the
      formation of chromatin loops that are shaped by the enhancer and the insulator.

PMID- 29045824
TI  - Enhanced doxorubicin delivery to hepatocellular carcinoma cells via CD147
      antibody-conjugated immunoliposomes.
AB  - HAb18G/CD147, an important marker in the progression of hepatocellular carcinoma
      (HCC), is highly expressed on the surface of HCC cells. To increase the
      therapeutic efficacy of Doxil (PEGylated liposomal doxorubicin) against HCC, we
      constructed CD147-targeted doxorubicin-loaded immunoliposomes (Anti-CD147 ILs
      DOX) by conjugating F(ab')2 of a CD147-specific monoclonal antibody to DSPE-PEG
      MAL, and then inserted the antibody-conjugated polymer to Doxil. Anti-CD147 ILs
      DOX delivered DOX to CD147-overexpressing HCC cells specifically and efficiently
      in vitro and in vivo, resulting in enhanced therapeutic effects than non-targeted
      controls. Strikingly, Anti-CD147 ILs-DOX reduced the CD133-positive fraction of
      HCC cells, suggesting its potential in reducing the number of HCC stem cells.
      Pharmacokinetic and biodistribution studies of Anti-CD147 ILs-DOX confirmed its
      long circulation time and efficient accumulation in tumors. The superior
      antitumor effects of Anti-CD147 ILs-DOX than other treatments were demonstrated
      in both HCC cells and patient-derived HCC xenograft models. Anti-CD147 ILs-DOX
      represent a novel approach for targeted HCC therapy.

PMID- 29045823
TI  - Traditional uses, phytochemistry and pharmacological properties of African
      Nauclea species: A review.
AB  - ETHNOPHARMACOALOGICAL RELEVANCE: The genus Nauclea in Africa comprises seven
      species. Among them, N. latifolia, N. diderrichii and N. pobeguinii are widely
      used by the local population in traditional remedies. Preparation from various
      parts of plants (e.g. roots, bark, leaves) are indicated by traditional healers
      for a wide range of diseases including malaria, pain, digestive ailments or
      metabolic diseases. MATERIALS AND METHODS: A literature search was conducted on
      African species of the genus Nauclea using scientific databases such as Google
      Scholar, Pubmed or SciFinder. Every document of ethnopharmacological,
      phytochemical or pharmacological relevance and written in English or French were
      analyzed. RESULTS AND DISCUSSION: The Nauclea genus is used as ethnomedicine all
      along sub-Saharan Africa. Several local populations consider Nauclea species as a
      major source of remedies for malaria. In this regard, two improved traditional
      medicines are currently under development using extracts from N. latifolia and N.
      pobeguinii. Concerning the chemical composition of the Nauclea genus,
      indoloquinolizidines alkaloids could be considered as the major class of
      compounds as they are reported in every analyzed Nauclea species, with numerous
      structures identified. Based on traditional indications a considerable amount of
      pharmacological studies were conducted to ensure activity and attempt to link
      them to the presence of particular compounds in plant extracts. CONCLUSION: Many
      experimental studies using plant extracts of the African species of the genus
      Nauclea validate traditional indications (e.g. malaria and pain). However,
      bioactive compounds are rarely identified and therefore, there is a clear need
      for further evaluations as well as for toxicity experiments. The sustainability
      of these plants, especially of N. diderrichii, a threatened species, should be
      kept in mind to adapt local uses and preparation modes of traditional remedies.

PMID- 29045825
TI  - Cerenkov luminescence imaging on evaluation of early response to chemotherapy of
      drug-resistant gastric cancer.
AB  - Apoptosis imaging enables a timely and specific assessment of treatment response
      in cancer patients. In this study, we applied a probe for positron emission
      tomography (PET), which served as an optical biomaterial emitting Cerenkov
      photons, to in vivo optical imaging of tumor apoptosis, in order to evaluate
      early response to chemotherapy of drug-resistant gastric cancer. 68Ga-DOTA
      Annexin V was prepared as the apoptosis targeting probe. Wild type human gastric
      adenocarcinoma cell line SGC7901/WT and drug vincristine-resistant variant
      SGC7901/VCR were used to establish normal and vincristine-resistant xenografts to
      simulate treatment decision situation. Vincristine-resistance of SGC7901/VCR and
      apoptosis-induction ability of vincristine and cisplatin were verified. In vitro
      and in vivo CLI of apoptosis was performed. Stronger signals of apoptosis of CLI
      correlated with confirmed higher levels of apoptosis and subsequent changes in
      tumor sizes. Our study suggests that CLI is a promising technique for in vivo
      imaging of apoptosis with radiopharmaceutical-labeled biomaterials.

PMID- 29045826
TI  - A Cell Migration Tracking Tool Supports Coupling of Tissue Rotation to
      Elongation.
AB  - Cell migration is indispensable to morphogenesis and homeostasis. Live imaging
      allows mechanistic insights, but long-term observation can alter normal biology,
      and tools to track movements in vivo without perturbation are lacking. We develop
      here a tool called M-TRAIL (matrix-labeling technique for real-time and inferred
      location), which reveals migration histories in fixed tissues. Using clones that
      overexpress GFP-tagged extracellular matrix (ECM) components, motility
      trajectories are mapped based on durable traces deposited onto basement membrane.
      We applied M-TRAIL to Drosophila follicle rotation, comparing in vivo and ex vivo
      migratory dynamics. The rate, trajectory, and cessation of rotation in wild-type
      (WT) follicles measured in vivo and ex vivo were identical, as was rotation
      failure in fat2 mutants. However, follicles carrying intracellularly truncated
      Fat2, previously reported to lack rotation ex vivo, in fact rotate in vivo at a
      reduced speed, thus revalidating the hypothesis that rotation is required for
      tissue elongation. The M-TRAIL approach could be applied to track and quantitate
      in vivo cell motility in other tissues and organisms.

PMID- 29045827
TI  - Yeast Srs2 Helicase Promotes Redistribution of Single-Stranded DNA-Bound RPA and
      Rad52 in Homologous Recombination Regulation.
AB  - Srs2 is a super-family 1 helicase that promotes genome stability by dismantling
      toxic DNA recombination intermediates. However, the mechanisms by which Srs2
      remodels or resolves recombination intermediates remain poorly understood. Here,
      single-molecule imaging is used to visualize Srs2 in real time as it acts on
      single-stranded DNA (ssDNA) bound by protein factors that function in
      recombination. We demonstrate that Srs2 is highly processive and translocates
      rapidly (~170 nt per second) in the 3'->5' direction along ssDNA saturated with
      replication protein A (RPA). We show that RPA is evicted from DNA during the
      passage of Srs2. Remarkably, Srs2 also readily removes the recombination mediator
      Rad52 from RPA-ssDNA and, in doing so, promotes rapid redistribution of both
      Rad52 and RPA. These findings have important mechanistic implications for
      understanding how Srs2 and related nucleic acid motor proteins resolve
      potentially pathogenic nucleoprotein intermediates.

PMID- 29045828
TI  - Prolonged IKKbeta Inhibition Improves Ongoing CTL Antitumor Responses by
      Incapacitating Regulatory T Cells.
AB  - Regulatory T cells (Tregs) prevent autoimmunity but limit antitumor immunity. The
      canonical NF-kappaB signaling pathway both activates immunity and promotes thymic
      Treg development. Here, we report that mature Tregs continue to require NF-kappaB
      signaling through IkappaB-kinase beta (IKKbeta) after thymic egress. Mice lacking
      IKKbeta in mature Tregs developed scurfy-like immunopathology due to death of
      peripheral FoxP3+ Tregs. Also, pharmacological IKKbeta inhibition reduced Treg
      numbers in the circulation by ~50% and downregulated FoxP3 and CD25 expression
      and STAT5 phosphorylation. In contrast, activated cytotoxic T lymphocytes (CTLs)
      were resistant to IKKbeta inhibition because other pathways, in particular
      nuclear factor of activated T cells (NFATc1) signaling, sustained their survival
      and expansion. In a melanoma mouse model, IKKbeta inhibition after CTL cross
      priming improved the antitumor response and delayed tumor growth. In conclusion,
      prolonged IKKbeta inhibition decimates circulating Tregs and improves CTL
      responses when commenced after tumor vaccination, indicating that IKKbeta
      represents a druggable checkpoint.

PMID- 29045829
TI  - Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the
      Absence of Replication Organelles.
AB  - Enteroviruses reorganize cellular endomembranes into replication organelles (ROs)
      for genome replication. Although enterovirus replication depends on
      phosphatidylinositol 4-kinase type IIIbeta (PI4KB), its role, and that of its
      product, phosphatidylinositol 4-phosphate (PI4P), is only partially understood.
      Exploiting a mutant coxsackievirus resistant to PI4KB inhibition, we show that
      PI4KB activity has distinct functions both in proteolytic processing of the viral
      polyprotein and in RO biogenesis. The escape mutation rectifies a proteolytic
      processing defect imposed by PI4KB inhibition, pointing to a possible escape
      mechanism. Remarkably, under PI4KB inhibition, the mutant virus could replicate
      its genome in the absence of ROs, using instead the Golgi apparatus. This
      impaired RO biogenesis provided an opportunity to investigate the proposed role
      of ROs in shielding enteroviral RNA from cellular sensors. Neither accelerated
      sensing of viral RNA nor enhanced innate immune responses was observed. Together,
      our findings challenge the notion that ROs are indispensable for enterovirus
      genome replication and immune evasion.

PMID- 29045830
TI  - In Vivo Suppression of HIV Rebound by Didehydro-Cortistatin A, a "Block-and-Lock"
      Strategy for HIV-1 Treatment.
AB  - HIV-1 Tat activates viral transcription and limited Tat transactivation
      correlates with latency establishment. We postulated a "block-and-lock"
      functional cure approach based on properties of the Tat inhibitor didehydro
      Cortistatin A (dCA). HIV-1 transcriptional inhibitors could block ongoing viremia
      during antiretroviral therapy (ART), locking the HIV promoter in persistent
      latency. We investigated this hypothesis in human CD4+ T cells isolated from
      aviremic individuals. Combining dCA with ART accelerates HIV-1 suppression and
      prevents viral rebound after treatment interruption, even during strong cellular
      activation. We show that dCA mediates epigenetic silencing by increasing
      nucleosomal occupancy at Nucleosome-1, restricting RNAPII recruitment to the HIV
      1 promoter. The efficacy of dCA was studied in the bone marrow-liver-thymus (BLT)
      mouse model of HIV latency and persistence. Adding dCA to ART-suppressed mice
      systemically reduces viral mRNA in tissues. Moreover, dCA significantly delays
      and reduces viral rebound levels upon treatment interruption. Altogether, this
      work demonstrates the potential of block-and-lock cure strategies.

PMID- 29045831
TI  - USP7 Is a Tumor-Specific WNT Activator for APC-Mutated Colorectal Cancer by
      Mediating beta-Catenin Deubiquitination.
AB  - The tumor suppressor gene adenomatous polyposis coli (APC) is mutated in most
      colorectal cancers (CRCs), resulting in constitutive Wnt activation. To
      understand the Wnt-activating mechanism of the APC mutation, we applied
      CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find
      that the beta-catenin inhibitory domain (CID) in APC represents the threshold for
      pathological levels of Wnt activation and tumor transformation. Mechanistically,
      CID-deleted APC truncation promotes beta-catenin deubiquitination through reverse
      binding of beta-TrCP and USP7 to the destruction complex. USP7 depletion in APC
      mutated CRC inhibits Wnt activation by restoring beta-catenin ubiquitination,
      drives differentiation, and suppresses xenograft tumor growth. Finally, the Wnt
      activating role of USP7 is specific to APC mutations; thus, it can be used as a
      tumor-specific therapeutic target for most CRCs.

PMID- 29045832
TI  - UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and
      Sensitizes Cells to EZH2 inhibition.
AB  - Loss or inactivation of the histone H3K27 demethylase UTX occurs in several
      malignancies, including multiple myeloma (MM). Using an isogenic cell system, we
      found that loss of UTX leads to deactivation of gene expression ultimately
      promoting the proliferation, clonogenicity, adhesion, and tumorigenicity of MM
      cells. Moreover, UTX mutant cells showed increased in vitro and in vivo
      sensitivity to inhibition of EZH2, a histone methyltransferase that generates
      H3K27me3. Such sensitivity was related to a decrease in the levels of IRF4 and c
      MYC and an activation of repressors of IRF4 characteristic of germinal center B
      cells such as BCL6 and IRF1. Rebalance of H3K27me3 levels at specific genes
      through EZH2 inhibitors may be a therapeutic strategy in MM cases harboring UTX
      mutations.

PMID- 29045833
TI  - Intestinal Fork Head Regulates Nutrient Absorption and Promotes Longevity.
AB  - Reduced activity of nutrient-sensing signaling networks can extend organismal
      lifespan, yet the underlying biology remains unclear. We show that the anti-aging
      effects of rapamycin and reduced intestinal insulin/insulin growth factor (IGF)
      signaling (IIS) require the Drosophila FoxA transcription factor homolog Fork
      Head (FKH). Intestinal FKH induction extends lifespan, highlighting a role for
      the gut. FKH binds to and is phosphorylated by AKT and Target of Rapamycin. Gut
      specific FKH upregulation improves gut barrier function in aged flies.
      Additionally, it increases the expression of nutrient transporters, as does
      lowered IIS. Evolutionary conservation of this effect of lowered IIS is suggested
      by the upregulation of related nutrient transporters in insulin receptor
      substrate 1 knockout mouse intestine. Our study highlights a critical role played
      by FKH in the gut in mediating anti-aging effects of reduced IIS. Malnutrition
      caused by poor intestinal absorption is a major problem in the elderly, and a
      better understanding of the mechanisms involved will have important therapeutic
      implications for human aging.

PMID- 29045834
TI  - A Latent Propriospinal Network Can Restore Diaphragm Function after High Cervical
      Spinal Cord Injury.
AB  - Spinal cord injury (SCI) above cervical level 4 disrupts descending axons from
      the medulla that innervate phrenic motor neurons, causing permanent paralysis of
      the diaphragm. Using an ex vivo preparation in neonatal mice, we have identified
      an excitatory spinal network that can direct phrenic motor bursting in the
      absence of medullary input. After complete cervical SCI, blockade of fast
      inhibitory synaptic transmission caused spontaneous, bilaterally coordinated
      phrenic bursting. Here, spinal cord glutamatergic neurons were both sufficient
      and necessary for the induction of phrenic bursts. Direct stimulation of phrenic
      motor neurons was insufficient to evoke burst activity. Transection and
      pharmacological manipulations showed that this spinal network acts independently
      of medullary circuits that normally generate inspiration, suggesting a distinct
      non-respiratory function. We further show that this "latent" network can be
      harnessed to restore diaphragm function after high cervical SCI in adult mice and
      rats.

PMID- 29045835
TI  - A Role for Dystonia-Associated Genes in Spinal GABAergic Interneuron Circuitry.
AB  - Spinal interneurons are critical modulators of motor circuit function. In the
      dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits
      proprioceptive sensory afferent terminals, thus negatively regulating sensory
      motor signaling. Although deficits in presynaptic inhibition have been inferred
      in human motor diseases, including dystonia, it remains unclear whether GABApre
      circuit components are altered in these conditions. Here, we use developmental
      timing to show that GABApre neurons are a late Ptf1a-expressing subclass and
      localize to the intermediate spinal cord. Using a microarray screen to identify
      genes expressed in this intermediate population, we find the kelch-like family
      member Klhl14, implicated in dystonia through its direct binding with torsion
      dystonia-related protein Tor1a. Furthermore, in Tor1a mutant mice in which Klhl14
      and Tor1a binding is disrupted, formation of GABApre sensory afferent synapses is
      impaired. Our findings suggest a potential contribution of GABApre neurons to the
      deficits in presynaptic inhibition observed in dystonia.

PMID- 29045836
TI  - Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural
      Dysfunction and Intelligence.
AB  - Arc is an activity-regulated neuronal protein, but little is known about its
      interactions, assembly into multiprotein complexes, and role in human disease and
      cognition. We applied an integrated proteomic and genetic strategy by targeting a
      tandem affinity purification (TAP) tag and Venus fluorescent protein into the
      endogenous Arc gene in mice. This allowed biochemical and proteomic
      characterization of native complexes in wild-type and knockout mice. We
      identified many Arc-interacting proteins, of which PSD95 was the most abundant.
      PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity
      dependent recruitment to excitatory synapses. Integrating human genetic data with
      proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia,
      intellectual disability, autism, and epilepsy mutations and normal variants in
      intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect
      human cognitive function.

PMID- 29045837
TI  - The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral
      Identity and Cone Photoreceptor Function.
AB  - Circadian clocks regulate various aspects of photoreceptor physiology, but their
      contribution to photoreceptor development and function is unclear. Cone
      photoreceptors are critical for color vision. Here, we define the molecular
      function of circadian activity within cone photoreceptors and reveal a role for
      the clock genes Bmal1 and Per2 in regulating cone spectral identity. ChIP
      analysis revealed that BMAL1 binds to the promoter region of the thyroid hormone
      (TH)-activating enzyme type 2 iodothyronine deiodinase (Dio2) and thus regulates
      the expression of Dio2. TH treatment resulted in a partial rescue of the
      phenotype caused by the loss of Bmal1, thus revealing a functional relationship
      between Bmal1 and Dio2 in establishing cone photoreceptor identity. Furthermore,
      Bmal1 and Dio2 are required to maintain cone photoreceptor functional integrity.
      Overall, our results suggest a mechanism by which circadian proteins can locally
      regulate the availability of TH and influence tissue development and function.

PMID- 29045839
TI  - Heterotopic Transplantations Reveal Environmental Influences on Interneuron
      Diversity and Maturation.
AB  - During embryogenesis, neural progenitors in the ganglionic eminences give rise to
      diverse GABAergic interneuron subtypes that populate all forebrain regions. The
      extent to which these cells are genetically predefined or determined by
      postmigratory environmental cues remains unknown. To address this question, we
      performed homo- and heterotopic transplantation of early postnatal MGE-derived
      cortical and hippocampal interneurons. Grafted cells migrated, and displayed
      neurochemical, electrophysiological, morphological, and neurochemical profiles
      similar to endogenous interneurons. Our results indicate that the host
      environment regulates the proportion of interneuron classes in the brain region.
      However, some specific interneuron subtypes retain characteristics representative
      of their donor brain regions.

PMID- 29045838
TI  - p75 Is Required for the Establishment of Postnatal Sensory Neuron Diversity by
      Potentiating Ret Signaling.
AB  - Producing the neuronal diversity required to adequately discriminate all elements
      of somatosensation is a complex task during organogenesis. The mechanisms guiding
      this process during dorsal root ganglion (DRG) sensory neuron specification
      remain poorly understood. Here, we show that the p75 neurotrophin receptor
      interacts with Ret and its GFRalpha co-receptor upon stimulation with glial cell
      line-derived neurotrophic factor (GDNF). Furthermore, we demonstrate that p75 is
      required for GDNF-mediated Ret activation, survival, and cell surface
      localization of Ret in DRG neurons. In mice in which p75 is deleted specifically
      within sensory neurons beginning at E12.5, we observe that approximately 20% of
      neurons are lost between P14 and adulthood, and these losses selectively occur
      within a subpopulation of Ret+ nonpeptidergic nociceptors, with neurons
      expressing low levels of Ret impacted most heavily. These results suggest that
      p75 is required for the development of the nonpeptidergic nociceptor lineage by
      fine-tuning Ret-mediated trophic support.

PMID- 29045840
TI  - Clonal Heterogeneity Influences the Fate of New Adaptive Mutations.
AB  - The joint contribution of pre-existing and de novo genetic variation to clonal
      adaptation is poorly understood but essential to designing successful
      antimicrobial or cancer therapies. To address this, we evolve genetically diverse
      populations of budding yeast, S. cerevisiae, consisting of diploid cells with
      unique haplotype combinations. We study the asexual evolution of these
      populations under selective inhibition with chemotherapeutic drugs by time
      resolved whole-genome sequencing and phenotyping. All populations undergo clonal
      expansions driven by de novo mutations but remain genetically and phenotypically
      diverse. The clones exhibit widespread genomic instability, rendering recessive
      de novo mutations homozygous and refining pre-existing variation. Finally, we
      decompose the fitness contributions of pre-existing and de novo mutations by
      creating a large recombinant library of adaptive mutations in an ensemble of
      genetic backgrounds. Both pre-existing and de novo mutations substantially
      contribute to fitness, and the relative fitness of pre-existing variants sets a
      selective threshold for new adaptive mutations.

PMID- 29045841
TI  - Phosphorylation of iRhom2 Controls Stimulated Proteolytic Shedding by the
      Metalloprotease ADAM17/TACE.
AB  - Cell surface metalloproteases coordinate signaling during development, tissue
      homeostasis, and disease. TACE (TNF-alpha-converting enzyme), is responsible for
      cleavage ("shedding") of membrane-tethered signaling molecules, including the
      cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within
      the secretory pathway requires its binding to iRhom2, which mediates the exit of
      TACE from the endoplasmic reticulum. An important, but mechanistically unclear,
      feature of TACE biology is its ability to be stimulated rapidly on the cell
      surface by numerous inflammatory and growth-promoting agents. Here, we report a
      role for iRhom2 in TACE stimulation on the cell surface. TACE shedding stimuli
      trigger MAP kinase-dependent phosphorylation of iRhom2 N-terminal cytoplasmic
      tail. This recruits 14-3-3 proteins, enforcing the dissociation of TACE from
      complexes with iRhom2, promoting the cleavage of TACE substrates. Our data reveal
      that iRhom2 controls multiple aspects of TACE biology, including stimulated
      shedding on the cell surface.

PMID- 29045843
TI  - High-Throughput Functional Genetic and Compound Screens Identify Targets for
      Senescence Induction in Cancer.
AB  - Senescence is a proliferation arrest that can result from a variety of stresses.
      Cancer cells can also undergo senescence, but the stresses that provoke cancer
      cells to undergo senescence are unclear. Here, we use both functional genetic and
      compound screens in cancer cells harboring a reporter that is activated during
      senescence to find targets that induce senescence. We show that suppression of
      the SWI/SNF component SMARCB1 induces senescence in melanoma through strong
      activation of the MAP kinase pathway. From the compound screen, we identified
      multiple aurora kinase inhibitors as potent inducers of senescence in RAS mutant
      lung cancer. Senescent melanoma and lung cancer cells acquire sensitivity to the
      BCL2 family inhibitor ABT263. We propose a one-two punch approach for the
      treatment of cancer in which a drug is first used to induce senescence in cancer
      cells and a second drug is then used to kill senescent cancer cells.

PMID- 29045842
TI  - The Conserved RNA Exonuclease Rexo5 Is Required for 3' End Maturation of 28S
      rRNA, 5S rRNA, and snoRNAs.
AB  - Non-coding RNA biogenesis in higher eukaryotes has not been fully characterized.
      Here, we studied the Drosophila melanogaster Rexo5 (CG8368) protein, a metazoan
      specific member of the DEDDh 3'-5' single-stranded RNA exonucleases, by genetic,
      biochemical, and RNA-sequencing approaches. Rexo5 is required for small nucleolar
      RNA (snoRNA) and rRNA biogenesis and is essential in D. melanogaster. Loss-of
      function mutants accumulate improperly 3' end-trimmed 28S rRNA, 5S rRNA, and
      snoRNA precursors in vivo. Rexo5 is ubiquitously expressed at low levels in
      somatic metazoan cells but extremely elevated in male and female germ cells. Loss
      of Rexo5 leads to increased nucleolar size, genomic instability, defective
      ribosome subunit export, and larval death. Loss of germline expression
      compromises gonadal growth and meiotic entry during germline development.

PMID- 29045844
TI  - A B Cell Regulome Links Notch to Downstream Oncogenic Pathways in Small B Cell
      Lymphomas.
AB  - Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas
      such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but
      the Notch target genes that contribute to B cell oncogenesis are largely unknown.
      We performed integrative analysis of Notch-regulated transcripts, genomic binding
      of Notch transcription complexes, and genome conformation data to identify direct
      Notch target genes in MCL cell lines. This B cell Notch regulome is largely
      controlled through Notch-bound distal enhancers and includes genes involved in B
      cell receptor and cytokine signaling and the oncogene MYC, which sustains
      proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage
      restricted enhancer complex. Expression of direct Notch target genes is
      associated with Notch activity in an MCL xenograft model and in CLL lymph node
      biopsies. Our findings provide key insights into the role of Notch in MCL and
      other B cell malignancies and have important implications for therapeutic
      targeting of Notch-dependent oncogenic pathways.

PMID- 29045845
TI  - Revealing the Determinants of Widespread Alternative Splicing Perturbation in
      Cancer.
AB  - It is increasingly appreciated that alternative splicing plays a key role in
      generating functional specificity and diversity in cancer. However, the
      mechanisms by which cancer mutations perturb splicing remain unknown. Here, we
      developed a network-based strategy, DrAS-Net, to investigate more than 2.5
      million variants across cancer types and link somatic mutations with cancer
      specific splicing events. We identified more than 40,000 driver variant
      candidates and their 80,000 putative splicing targets deregulated in 33 cancer
      types and inferred their functional impact. Strikingly, tumors with splicing
      perturbations show reduced expression of immune system-related genes and
      increased expression of cell proliferation markers. Tumors harboring different
      mutations in the same gene often exhibit distinct splicing perturbations. Further
      stratification of 10,000 patients based on their mutation-splicing relationships
      identifies subtypes with distinct clinical features, including survival rates.
      Our work reveals how single-nucleotide changes can alter the repertoires of
      splicing isoforms, providing insights into oncogenic mechanisms for precision
      medicine.

PMID- 29045846
TI  - Identification of Genetically Intact HIV-1 Proviruses in Specific CD4+ T Cells
      from Effectively Treated Participants.
AB  - Latent replication-competent HIV-1 persists in individuals on long-term
      antiretroviral therapy (ART). We developed the Full-Length Individual Proviral
      Sequencing (FLIPS) assay to determine the distribution of latent replication
      competent HIV-1 within memory CD4+ T cell subsets in six individuals on long-term
      ART. FLIPS is an efficient, high-throughput assay that amplifies and sequences
      near full-length (~9 kb) HIV-1 proviral genomes and determines potential
      replication competency through genetic characterization. FLIPS provides a genome
      scale perspective that addresses the limitations of other methods that also
      genetically characterize the latent reservoir. Using FLIPS, we identified 5% of
      proviruses as intact and potentially replication competent. Intact proviruses
      were unequally distributed between T cell subsets, with effector memory cells
      containing the largest proportion of genetically intact HIV-1 proviruses. We
      identified multiple identical intact proviruses, suggesting a role for cellular
      proliferation in the maintenance of the latent HIV-1 reservoir.

PMID- 29045847
TI  - Cross-Tissue Transcriptomic Analysis of Human Secondary Lymphoid Organ-Residing
      ILC3s Reveals a Quiescent State in the Absence of Inflammation.
AB  - A substantial number of human and mouse group 3 innate lymphoid cells (ILC3s)
      reside in secondary lymphoid organs, yet the phenotype and function of these
      ILC3s is incompletely understood. Here, we employed an unbiased cross-tissue
      transcriptomic approach to compare human ILC3s from non-inflamed lymph nodes and
      spleen to their phenotypic counterparts in inflamed tonsils and from circulation.
      These analyses revealed that, in the absence of inflammation, lymphoid organ
      residing ILC3s lack transcription of cytokines associated with classical ILC3
      functions. This was independent of expression of the natural cytotoxicity
      receptor NKp44. However, and in contrast to ILC3s from peripheral blood, lymphoid
      organ-residing ILC3s express activating cytokine receptors and have acquired the
      ability to be recruited into immune responses by inflammatory cytokines. This
      comprehensive cross-tissue dataset will allow for identification of functional
      changes in human lymphoid organ ILC3s associated with human disease.

PMID- 29045848
TI  - Single-Molecule Sequencing Reveals the Chromosome-Scale Genomic Architecture of
      the Nematode Model Organism Pristionchus pacificus.
AB  - The nematode Pristionchus pacificus is an established model for integrative
      evolutionary biology and comparative studies with Caenorhabditis elegans. While
      an existing genome draft facilitated the identification of several genes
      controlling various developmental processes, its high degree of fragmentation
      complicated virtually all genomic analyses. Here, we present a de novo genome
      assembly from single-molecule, long-read sequencing data consisting of 135 P.
      pacificus contigs. When combined with a genetic linkage map, 99% of the assembly
      could be ordered and oriented into six chromosomes. This allowed us to robustly
      characterize chromosomal patterns of gene density, repeat content, nucleotide
      diversity, linkage disequilibrium, and macrosynteny in P. pacificus. Despite
      widespread conservation of synteny between P. pacificus and C. elegans, we
      identified one major translocation from an autosome to the sex chromosome in the
      lineage leading to C. elegans. This highlights the potential of the chromosome
      scale assembly for future genomic studies of P. pacificus.

PMID- 29045849
TI  - A Synthetic Oligo Library and Sequencing Approach Reveals an Insulation Mechanism
      Encoded within Bacterial sigma54 Promoters.
AB  - We use an oligonucleotide library of >10,000 variants to identify an insulation
      mechanism encoded within a subset of sigma54 promoters. Insulation manifests
      itself as reduced protein expression for a downstream gene that is expressed by
      transcriptional readthrough. It is strongly associated with the presence of short
      CT-rich motifs (3-5 bp), positioned within 25 bp upstream of the Shine-Dalgarno
      (SD) motif of the silenced gene. We provide evidence that insulation is triggered
      by binding of the ribosome binding site (RBS) to the upstream CT-rich motif. We
      also show that, in E. coli, insulator sequences are preferentially encoded within
      sigma54 promoters, suggesting an important regulatory role for these sequences in
      natural contexts. Our findings imply that sequence-specific regulatory effects
      that are sparsely encoded by short motifs may not be easily detected by lower
      throughput studies. Such sequence-specific phenomena can be uncovered with a
      focused oligo library (OL) design that mitigates sequence-related variance, as
      exemplified herein.

PMID- 29045851
TI  - Trends in pelvic inflammatory disease emergency department visits, United States,
      2006-2013.
AB  - BACKGROUND: Pelvic inflammatory disease is a female genital tract disorder with
      severe reproductive sequelae. Because of the difficulties in diagnosing pelvic
      inflammatory disease, it is not a reportable condition in many states. Females
      seeking care in emergency departments are a sentinel population for pelvic
      inflammatory disease surveillance. OBJECTIVE: The objective of the study was to
      determine trends in diagnoses of acute pelvic inflammatory disease in a
      nationally representative sample of emergency departments. STUDY DESIGN: All
      emergency department visits among females aged 15-44 years with an International
      Classification of Diseases, ninth revision, Clinical Modification diagnosis code
      indicating pelvic inflammatory disease during 2006-2013 were assessed from the
      HealthCare Utilization Project Nationwide Emergency Department Sample. Total and
      annual percentage changes in the proportion of pelvic inflammatory disease
      emergency department visits were estimated using trend analyses. RESULTS: While
      the number of emergency department visits among females aged 15-44 years during
      2006-2013 increased (6.5 million to 7.4 million), the percentage of visits due to
      pelvic inflammatory disease decreased from 0.57% in 2006 to 0.41% in 2013 (total
      percentage change, -28.4%; annual percent change, -4.3%; 95% confidence interval,
      -5.7% to -2.9%). The largest decreases were among those aged 15-19 years (total
      percent change, -40.6%; annual percentage change, -6.6%; 95% confidence interval,
      -8.6% to -4.4%) and living in the South (total percentage change, -38.0%; annual
      percentage change, -6.2%; 95% confidence interval, -7.8% to -4.6%). Females aged
      15-19 years who lived in the South had a 47.9% decrease in visits due to pelvic
      inflammatory disease (annual percentage change, -8.4%, 95% confidence interval, 
      10.4 to -6.5). Patients living in ZIP codes with the lowest median income
      (<$38,000) had the highest percent of visits with a pelvic inflammatory disease
      diagnosis; the smallest declines over time were in patients living in ZIP codes
      with the highest median income (i.e., >$64,000, total percent change, -24.4%;
      annual percent change, -3.8%; 95% confidence interval, -5.2% to -2.4%). The
      percentage of emergency department visits due to pelvic inflammatory disease was
      highest among patients not charged for their visit, self-paying, or those covered
      by Medicaid, with total percentage changes in these 3 groups of -27.8%, -30.7%,
      and -35.1%, respectively. Patients with Medicaid coverage had the largest
      decrease in visits with a diagnosis of pelvic inflammatory disease (total percent
      change, -35.1%; annual percent change, -5.8%; 95% confidence interval, -7.2% to 
      4.3%). CONCLUSION: Nationally representative data indicate the percentage of
      emergency department visits with a pelvic inflammatory disease diagnosis
      decreased during 2006-2013 among females aged 15-44 years, primarily driven by
      decreased diagnoses of pelvic inflammatory disease among females aged 15-19 years
      and among women living in the southern United States. Despite declines, a large
      number of females of reproductive age are receiving care for pelvic inflammatory
      disease in emergency departments. Patients with lower median income and no or
      public health insurance status, which may decrease access to and use of health
      care services, consistently had the highest percentage of emergency department
      visits due to pelvic inflammatory disease. Future research should focus on
      obtaining a better understanding of factors influencing trends in pelvic
      inflammatory disease diagnoses and ways to address the challenges surrounding
      surveillance for this condition.

PMID- 29045850
TI  - Comparison of conventional 2D ultrasound to magnetic resonance imaging for
      prenatal estimation of birthweight in twin pregnancy.
AB  - BACKGROUND: During prenatal follow-up of twin pregnancies, accurate
      identification of birthweight and birthweight discordance is important to
      identify the high-risk group and plan perinatal care. Unfortunately, prenatal
      evaluation of birthweight discordance by 2-dimensional ultrasound has been far
      from optimal. OBJECTIVE: The objective of the study was to prospectively compare
      estimates of fetal weight based on 2-dimensional ultrasound (ultrasound-estimated
      fetal weight) and magnetic resonance imaging (magnetic resonance-estimated fetal
      weight) with actual birthweight in women carrying twin pregnancies. STUDY DESIGN:
      Written informed consent was obtained for this ethics committee-approved study.
      Between September 2011 and December 2015 and within 48 hours before delivery,
      ultrasound-estimated fetal weight and magnetic resonance-estimated fetal weight
      were conducted in 66 fetuses deriving from twin pregnancies at 34.3-39.0 weeks;
      gestation. Magnetic resonance-estimated fetal weight derived from manual
      measurement of fetal body volume. Comparison of magnetic resonance-estimated
      fetal weight and ultrasound-estimated fetal weight measurements vs birthweight
      was performed by calculating parameters as described by Bland and Altman.
      Receiver-operating characteristic curves were constructed for the prediction of
      small-for-gestational-age neonates using magnetic resonance-estimated fetal
      weight and ultrasound-estimated fetal weight. For twins 1 and 2 separately, the
      relative error or percentage error was calculated as follows: (birthweight -
      ultrasound-estimated fetal weight (or magnetic resonance-estimated fetal
      weight)/birthweight) * 100 (percentage). Furthermore, ultrasound-estimated fetal
      weight, magnetic resonance-estimated fetal weight, and birthweight discordance
      were calculated as 100 * (larger estimated fetal weight-smaller estimated fetal
      weight)/larger estimated fetal weight. The ultrasound-estimated fetal weight
      discordance and the birthweight discordance were correlated using linear
      regression analysis and Pearson's correlation coefficient. The same was done
      between the magnetic resonance-estimated fetal weight and birthweight
      discordance. To compare data, the chi2, McNemar test, Student t test, and
      Wilcoxon signed rank test were used as appropriate. We used the Fisher r-to-z
      transformation to compare correlation coefficients. RESULTS: The bias and the 95%
      limits of agreement of ultrasound-estimated fetal weight are 2.99 (-19.17% to
      25.15%) and magnetic resonance-estimated fetal weight 0.63 (-9.41% to 10.67%).
      Limits of agreement were better between magnetic resonance-estimated fetal weight
      and actual birthweight as compared with the ultrasound-estimated fetal weight. Of
      the 66 newborns, 27 (40.9%) were of weight of the 10th centile or less and 21
      (31.8%) of the fifth centile or less. The area under the receiver-operating
      characteristic curve for prediction of birthweight the 10th centile or less by
      prenatal ultrasound was 0.895 (P < .001; SE, 0.049), and by magnetic resonance
      imaging it was 0.946 (P < .001; SE, 0.024). Pairwise comparison of receiver
      operating characteristic curves showed a significant difference between the areas
      under the receiver-operating characteristic curves (difference, 0.087, P = .049;
      SE, 0.044). The relative error for ultrasound-estimated fetal weight was 6.8% and
      by magnetic resonance-estimated fetal weight, 3.2% (P < .001). When using
      ultrasound-estimated fetal weight, 37.9% of fetuses (25 of 66) were estimated
      outside the range of +/-10% of the actual birthweight, whereas this dropped to
      6.1% (4 of 66) with magnetic resonance-estimated fetal weight (P < .001). The
      ultrasound-estimated fetal weight discordance and the birthweight discordance
      correlated significantly following the linear equation: ultrasound-estimated
      fetal weight discordance = 0.03 + 0.91 * birthweight (r = 0.75; P < .001);
      however, the correlation was better with magnetic resonance imaging: magnetic
      resonance-estimated fetal weight discordance = 0.02 + 0.81 * birthweight (r =
      0.87; P < .001). CONCLUSION: In twin pregnancies, magnetic resonance-estimated
      fetal weight performed immediately prior to delivery is more accurate and
      predicts small-for-gestational-age neonates significantly better than ultrasound
      estimated fetal weight. Prediction of birthweight discordance is better with
      magnetic resonance imaging as compared with ultrasound.

PMID- 29045852
TI  - Surgery for Herniated Lumbar Disc in Daily Tobacco Smokers: A Multicenter
      Observational Study.
AB  - OBJECTIVE: To compare clinical outcomes at 1 year following single-level lumbar
      microdiscectomy in daily tobacco smokers and nonsmokers. METHODS: Data were
      collected through the Norwegian Registry for Spine Surgery. The primary endpoint
      was a change in the Oswestry Disability Index (ODI) at 1 year. Secondary
      endpoints were change in quality of life measured with EuroQol 5 Dimensions (EQ
      5D), leg and back pain measured with a numerical rating scale (NRS), and rates of
      surgical complications. RESULTS: A total of 5514 patients were enrolled,
      including 3907 nonsmokers and 1607 smokers. A significant improvement in ODI was
      observed for the entire cohort (mean, 31.1 points; 95% confidence interval [CI],
      30.4-31.8; P < 0.001). Nonsmokers experienced a greater improvement in ODI at 1
      year compared with smokers (mean, 4.1 points; 95% CI, 2.5-5.7; P < 0.001).
      Nonsmokers were more likely to achieve a minimal important change (MIC), defined
      as an ODI improvement of >=10 points, compared with smokers (85.5% vs. 79.5%; P <
      0.001). Nonsmokers experienced greater improvements in EQ-5D (mean difference,
      0.068; 95% CI, 0.04-0.09; P < 0.001), back pain NRS (mean difference, 0.44; 95%
      CI, 0.21-0.66; P < 0.001), and leg pain NRS (mean difference, 0.54; 95% CI, 0.31
      0.77; P < 0.001). There was no difference between smokers and nonsmokers in the
      overall complication rate (6.2% vs. 6.7%; P = 0.512). Smoking was identified as a
      negative predictor for ODI change in a multiple regression analysis (P < 0.001).
      CONCLUSIONS: Nonsmokers reported a greater improvement in ODI at 1 year following
      microdiscectomy, and smokers were less likely to experience an MIC. Nonetheless,
      significant improvement was also found among smokers.

PMID- 29045853
TI  - Symptomatic Vasospasms as a Life-Threatening Complication After Transsphenoidal
      Surgery.
AB  - OBJECTIVE: To identify symptomatic vasospasms as a rare complication after
      transsphenoidal surgery, with emphasis on management and outcomes. METHODS: In
      this retrospective study, the medical records of 1997 patients who underwent
      microscopic transsphenoidal surgery at our hospital between 2008 and 2016 were
      analyzed regarding postoperative vasospasm events, clinical management, and
      neurologic outcomes. RESULTS: Four patients (0.2%) were identified who developed
      neurologic deficits in the postoperative phase caused by proven vasospasms due to
      subarachnoid hemorrhage (SAH). All 4 patients were treated according to current
      state-of-the-art recommendations for SAH-triggered vasospasms and, as ultima
      ratio, intra-arterial spasmolysis. Nonetheless, all patients developed
      multilocular ischemic infarctions. Three patients recovered with no or only
      slight neurologic deficits (2 with a Glasgow Outcome Score [GOS] of 5; 1 with a
      GOS of 4), and 1 patient died, at 24 days after surgery. CONCLUSIONS: Although a
      rare complication, vasospasms after transsphenoidal surgery can lead to severe
      and multilocular ischemic infarctions with a wide variety of neurologic
      impairments. This rare complication should be considered in patients with
      unexpected postoperative neurologic deficits. Computed tomography (CT)/magnetic
      resonance imaging and (contrast-enhanced) CT/magnetic resonance angiography are
      appropriate diagnostic tools. Treatment of vasospasms, including the option of
      intra-arterial spasmolysis, should not be delayed.

PMID- 29045854
TI  - Efficacy of Cone Beam Computed Tomography in Treating Cavernous Sinus Dural
      Arteriovenous Fistula.
AB  - BACKGROUND: Exact identification of feeding arteries, shunt points, and draining
      veins is essential in treating cavernous sinus dural arteriovenous fistula (CS
      dAVF). In addition to digital subtraction angiography (DSA) and 3-dimensional
      rotational angiography (3DRA), high-resolution cone beam computed tomography
      (CBCT; especially 80-kv high-resolution cone beam computed tomography) have been
      performed in recent years. We evaluated the efficacy of CBCT in treating CS dAVF.
      METHODS: Eight CS dAVFs were treated with endovascular embolization between
      January 2013 and December 2016. We retrospectively examined these cases regarding
      information from DSA, 3DRA, and CBCT with contrast medium. RESULTS: Although all
      procedures can evaluate feeding arteries, shunt points, and draining veins, CBCT
      can provide the best definition of feeders and their course through the bony
      structures and the compartment of CS. Therefore, CBCT with placed microcatheter
      in the CS can reveal whether the microcatheter is set at the appropriate
      compartment to be embolized. CONCLUSIONS: The efficacy of CBCT in treating dAVF
      is illustrating the relationships among the bony structures and feeders,
      compartment of CS, and the position of the microcatheter. Detailed information
      obtained with CBCT can lead to fewer complications and more effective treatment.

PMID- 29045855
TI  - Prognostic Factors in Skull Base Chordoma: A Systematic Literature Review and
      Meta-Analysis.
AB  - OBJECTIVE: Currently, there are a lack of reviews assessing the complete range of
      prognostic factors in skull base chordoma (SBC). This study aimed to
      systematically review the published literature on prognostic factors in SBC and
      establish pooled hazard ratios (HRs) of such factors. METHODS: MEDLINE and Embase
      searches (inception to April 4, 2017) were conducted. Two reviewers independently
      selected papers involving SBC prognostic factors, and studied them for
      methodologic quality and valuable factors. Pooled HRs and 95% confidence
      intervals (CIs) were calculated. The main end points determined were progression
      free survival (PFS) and overall survival (OS). RESULTS: Twenty-two studies with
      1754 subjects were included in this systematic review. However, only 18 of the
      studies provided sufficient data for quantitative synthesis. Preoperative visual
      deficit (pooled HR, 2.77; 95% CI, 1.57-4.89 for PFS), older patient age (pooled
      HR, 1.03; 95% CI, 1.1-1.05 for PFS; pooled HR, 1.03; 95% CI, 1.2-1.04 for OS),
      and nontotal or intralesional tumor resection (pooled HR, 2.01; 95% CI, 1.54-2.62
      for PFS; pooled HR, 5.16; 95% CI, 2.27-11.70 for OS) were negative predictors of
      survival outcomes. However, adjunctive radiotherapy (pooled HR, 0.30; 95% CI,
      0.16-0.56) and chondroid chordoma type (pooled HR, 0.5; 95% CI, 0.36-0.69)
      portended a favorable PFS. In addition, several prognostic biomarkers were
      promising. CONCLUSIONS: This study demonstrated that several clinicopathologic or
      molecular parameters are associated with survival up to tumor progression or
      mortality in SBC patients. However, further methodologically high-quality reports
      are still required to clarify the effects of these factors.

PMID- 29045856
TI  - Direction of stimulus movement alters fear-linked individual differences in
      attentional vigilance to spider stimuli.
AB  - Researchers have proposed that high spider-fearful individuals are characterised
      by heightened attentional vigilance to spider stimuli, as compared to low spider
      fearful individuals. However, these findings have arisen from methodologies that
      have uniformly employed only static stimuli. Such findings do not inform upon the
      patterns of fear-linked attentional selectivity that occur in the face of moving
      feared stimuli. Hence, the present study developed a novel methodology designed
      to examine the influence of stimulus movement on attentional vigilance to spider
      and non-spider stimuli. Eighty participants who varied in level of spider-fear
      completed an attentional-probe task that presented stimuli under two conditions.
      One condition presented stimuli that displayed an approaching movement, while the
      other condition presented stimuli that displayed a receding movement. Fear-linked
      heightened attentional vigilance was observed exclusively under the latter
      condition. These findings suggest that fear-linked attentional vigilance to
      spider stimuli does not represent a uniform characteristic of heightened spider
      fear, but rather is influenced by stimulus context. The means by which these
      findings inform understanding of attentional mechanisms that characterise
      heightened spider-fear, and avenues for future research, are discussed.

PMID- 29045857
TI  - A Systematic Review and Meta-Analysis on the Use of Repetitive Transcranial
      Magnetic Stimulation for Spasticity Poststroke.
AB  - BACKGROUND: Spasticity is a common and potentially debilitating complication that
      develops after stroke, arising in approximately 30% of patients. OBJECTIVE: To
      evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS)
      in improving spasticity after stroke. DESIGN: Meta-analysis and systematic
      review. SETTING: Not applicable. PATIENTS: A total of 273 poststroke (hemorrhagic
      = 123, ischemic = 150) participants were included with sample sizes ranging from
      5 to 80. The majority of participants were male (66.0%) with a mean age ranging
      from 55.0 to 64.6 years. Mean stroke duration ranged from 6 months to 10 years.
      METHODS: A literature search of multiple databases was conducted for articles
      published in English from January 1980 to April 2015 using select keywords.
      Studies were included if (1) the population included was >50% stroke patients;
      (2) the sample size included >=4 subjects; (3) the intervention applied was rTMS;
      and (4) upper extremity spasticity was assessed pre- and postintervention.
      Randomized controlled trials (RCTs) were assessed for methodologic quality with
      the Physiotherapy Evidence Database tool. All research designs were given a level
      of evidence according to a modified Sackett Scale. MAIN OUTCOME MEASUREMENTS:
      Modified Ashworth Scale (MAS). RESULTS: Ten studies met the inclusion criteria: 2
      RCTs (Physiotherapy Evidence Database scores 8-9) and 8 pre-post studies. Meta
      analyses of primarily uncontrolled pre-post studies found significant
      improvements in MAS for elbow (P < .001), wrist (P < .001), and finger flexors (P
      < .001). However, a meta-analysis of the 2 available RCTs failed to find a
      significant rTMS treatment effect on MAS for the wrist (standardized difference =
      .34, P = .30). CONCLUSIONS: There is limited available evidence to support the
      use of rTMS in improving spasticity poststroke. Despite the positive findings
      reported, better powered and appropriately controlled trials are necessary. LEVEL
      OF EVIDENCE: II.

PMID- 29045858
TI  - Circulating circular RNA hsa_circ_0001785 acts as a diagnostic biomarker for
      breast cancer detection.
AB  - BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) and
      characterized by covalently closed loop without 5' and 3' end. Recently, the
      diagnostic value of circRNAs has received more and more attention. However, the
      in-depth study about circRNAs diagnosis in breast cancer is still rarely
      reported. In present study, we try to investigate the circRNAs expression
      profiles in breast cancer peripheral blood and discover valuable diagnostic
      biomarkers. METHODS: The expression profiles of circRNAs in plasma specimens were
      screened from five breast cancer and paired healthy volunteer s. The expression
      levels of selected candidate circRNAs were detected by RT-PCR. The diagnostic
      value was performed using receiver operating characteristic (ROC) curve. RESULTS:
      CircRNAs microarray assay showed that 41 circRNAs were aberrantly expressed with
      2 fold change, including 19 up-regulated and 22 down-regulated circRNAs. Among
      these circRNAs, 3 candidate circRNAs were validated to be significantly
      dysregulated using RT-PCR, including hsa_circ_0001785, hsa_circ_0108942 and
      hsa_circ_0068033. In lager study cohort (n=20), ROC curve showed that
      hsa_circ_0001785 had better diagnostic value (AUC=0.771) than others. Moreover,
      in further extensive study cohort (n=57), we found that hsa_circ_0001785 plasma
      had better diagnostic accuracy (AUC=0.784) than CEA (AUC=0.562) and CA15-3
      (AUC=0.629). Besides, hsa_circ_0001785 plasma level was closely related to
      histological grade (P=0.013), TNM stage (P=0.008) and distant metastasis
      (P=0.016). Furthermore, hsa_circ_0001785 plasma level in postoperative patients
      (0.283+/-0.043) was significantly lower than that of preoperative patients
      (0.109+/-0.037, P<0.01). CONCLUSION: Our study reveals the aberrant circRNAs
      expression profiles in breast cancer peripheral blood, and identifies the
      potential diagnostic value of plasma hsa_circ_0001785, providing a stable
      biomarkers for the diagnosis and progress of breast cancer.

PMID- 29045859
TI  - Role of Condensing Particles in Polymer Confinement: A Model for Virus-Packed
      "Minichromosomes".
AB  - Confined mixtures of a polymer and nonspecifically binding particles (condensers)
      are studied as models for viruses containing double-stranded DNA (polymer) and
      condensing proteins (particles). We explore a model in which all interactions
      between the packed content (polymer and particles) and its confinement are purely
      repulsive, with only a short-range attraction between the condensers and polymer
      to simulate binding. In the range of physical parameters applicable to viruses,
      the model predicts reduction of pressure in the system effected by the
      condensers, despite the reduction in free volume. Condensers are found to be
      interspersed throughout the spherical confinement and only partially wrapped in
      the polymer, which acts as an effective medium for the condenser interactions.
      Crowding of the viral interior influences the DNA and protein organization,
      producing a picture inconsistent with a chromatin-like, beads-on-a-string
      structure. The model predicts an organization of the confined interior compatible
      with experimental data on unperturbed adenoviruses and polyomaviruses, at the
      same time providing insight into the role of condensing proteins in the viral
      infectious cycles of related viral families.

PMID- 29045860
TI  - Mechanics and Buckling of Biopolymeric Shells and Cell Nuclei.
AB  - We study a Brownian dynamics simulation model of a biopolymeric shell deformed by
      axial forces exerted at opposing poles. The model exhibits two distinct, linear
      force-extension regimes, with the response to small tensions governed by linear
      elasticity and the response to large tensions governed by an effective spring
      constant that scales with radius as R-0.25. When extended beyond the initial
      linear elastic regime, the shell undergoes a hysteretic, temperature-dependent
      buckling transition. We experimentally observe this buckling transition by
      stretching and imaging the lamina of isolated cell nuclei. Furthermore, the
      interior contents of the shell can alter mechanical response and buckling, which
      we show by simulating a model for the nucleus that quantitatively agrees with our
      micromanipulation experiments stretching individual nuclei.

PMID- 29045861
TI  - Effects of Nanopore Charge Decorations on the Translocation Dynamics of DNA.
AB  - We have investigated the dynamics of single-stranded DNA as it translocates
      through charge-mutated protein nanopores. Translocation of DNA is a crucial step
      in nanopore-based sequencing platforms, where control over translocation speed
      remains one of the main challenges. Taking advantage of the interactions between
      negatively charged DNA and positively charged amino acid residues, the
      translocation speed of DNA can be manipulated by deliberate charge decorations
      inside the nanopore. We employed coarse-grained Langevin dynamics simulations to
      monitor the step-by-step movement of DNA through different mutations of alpha
      hemolysin protein nanopores. We found that although the average translocation
      time per nucleotide is longer, in agreement with experiments, the DNA nucleotides
      do not translocate with a uniform speed. Furthermore, the location and spacing of
      the charge decorations can alter the translocation dynamics significantly,
      trapping DNA in some cases. Our findings can give insights when designing charge
      patterns in nanopores.

PMID- 29045862
TI  - The Two-State Prehensile Tail of the Antibacterial Toxin Colicin N.
AB  - Intrinsically disordered regions within proteins are critical elements in many
      biomolecular interactions and signaling pathways. Antibacterial toxins of the
      colicin family, which could provide new antibiotic functions against resistant
      bacteria, contain disordered N-terminal translocation domains (T-domains) that
      are essential for receptor binding and the penetration of the Escherichia coli
      outer membrane. Here we investigate the conformational behavior of the T-domain
      of colicin N (ColN-T) to understand why such domains are widespread in toxins
      that target Gram-negative bacteria. Like some other intrinsically disordered
      proteins in the solution state of the protein, ColN-T shows dual recognition,
      initially interacting with other domains of the same colicin N molecule and
      later, during cell killing, binding to two different receptors, OmpF and TolA, in
      the target bacterium. ColN-T is invisible in the high-resolution x-ray model and
      yet accounts for 90 of the toxin's 387 amino acid residues. To reveal its
      solution structure that underlies such a dynamic and complex system, we carried
      out mutagenic, biochemical, hydrodynamic and structural studies using analytical
      ultracentrifugation, NMR, and small-angle x-ray scattering on full-length ColN
      and its fragments. The structure was accurately modeled from small-angle x-ray
      scattering data by treating ColN as a flexible system, namely by the ensemble
      optimization method, which enables a distribution of conformations to be included
      in the final model. The results reveal, to our knowledge, for the first time the
      dynamic structure of a colicin T-domain. ColN-T is in dynamic equilibrium between
      a compact form, showing specific self-recognition and resistance to proteolysis,
      and an extended form, which most likely allows for effective receptor binding.

PMID- 29045863
TI  - High-Pressure-Driven Reversible Dissociation of alpha-Synuclein Fibrils Reveals
      Structural Hierarchy.
AB  - The analysis of the alpha-synuclein (aS) aggregation process, which is involved
      in Parkinson's disease etiopathogenesis, and of the structural feature of the
      resulting amyloid fibrils may shed light on the relationship between the
      structure of aS aggregates and their toxicity. This may be considered a paradigm
      of the ground work needed to tackle the molecular basis of all the protein
      aggregation-related diseases. With this aim, we used chemical and physical
      dissociation methods to explore the structural organization of wild-type aS
      fibrils. High pressure (in the kbar range) and alkaline pH were used to
      disassemble fibrils to collect information on the hierarchic pathway by which
      distinct beta-sheets sequentially unfold using the unique possibility offered by
      high-pressure Fourier transform infrared spectroscopy. The results point toward
      the formation of kinetic traps in the energy landscape of aS fibril disassembly
      and the presence of transient partially folded species during the process. Since
      we found that the dissociation of wild-type aS fibrils by high pressure is
      reversible upon pressure release, the disassembled molecules likely retain
      structural information that favors fibril reformation. To deconstruct the role of
      the different regions of aS sequence in this process, we measured the high
      pressure dissociation of amyloids formed by covalent chimeric dimers of aS (syn
      syn) and by the aS deletion mutant that lacks the C-terminus, i.e., aS (1-99).
      The results allowed us to single out the role of dimerization and that of the C
      terminus in the complete maturation of fibrillar aS.

PMID- 29045864
TI  - Molecular Simulations Suggest a Force-Dependent Mechanism of Vinculin Activation.
AB  - Focal adhesions are dynamic constructs at the leading edge of migrating cells,
      linking them to the extracellular matrix and enabling force sensing and
      transmission. The lifecycle of a focal adhesion is a highly coordinated process
      involving spatial and temporal variations of protein composition, interaction,
      and cellular tension. The assembly of focal adhesions requires the recruitment
      and activation of vinculin. Vinculin is present in the cytoplasm in an
      autoinhibited conformation in which its tail is held pincerlike by its head
      domains, further stabilized by two high-affinity head-tail interfaces. Vinculin
      has binding sites for talin and F-actin, but effective binding requires vinculin
      activation to release its head-tail associations. In migrating cells, it has been
      shown that the locations of vinculin activation coincide with areas of high
      cellular tension, and that the highest recorded tensions across vinculin are
      associated with adhesion assembly. Here, we use a structure-based model to
      investigate vinculin activation by talin modulated by tensile force generated by
      transient associations with F-actin. We show that vinculin activation may proceed
      from an intermediate state stabilized by partial talin-vinculin association.
      There is a low-force regime and a high-force regime where vinculin activation is
      dominated by two different pathways with distinct responses to force.
      Specifically, at zero or low forces, vinculin activation requires substantial
      destabilization of the main head-tail interface, which is rigid and undergoes
      very limited fluctuations, despite the other being relatively flexible. This
      pathway is not significantly affected by force; instead, higher forces favor an
      alternative pathway, which seeks to release the vinculin tail from its pincerlike
      head domains before destabilizing the head-tail interfaces. This pathway has a
      force-sensitive activation barrier and is significantly accelerated by force.
      Experimental data of vinculin during various stages of the focal adhesion
      lifecycle are consistent with the proposed force-regulated activation pathway.

PMID- 29045865
TI  - Cooperative Nucleotide Binding in Hsp90 and Its Regulation by Aha1.
AB  - The function of the molecular chaperone Hsp90 depends on large conformational
      changes, the rearrangement of local motifs, and the binding and hydrolysis of
      ATP. The size and complexity of the Hsp90 system impedes the detailed
      investigation of their interplay using standard methods. To overcome this
      limitation, we developed a three-color single-molecule FRET assay to study the
      interaction of Hsp90 with a fluorescently labeled reporter nucleotide in detail.
      It allows us to directly observe the cooperativity between the two nucleotide
      binding pockets in the protein dimer. Furthermore, our approach disentangles the
      protein conformation and the nucleotide binding state of Hsp90 and extracts the
      kinetics of the state transitions. Thereby, we can identify the kinetic causes
      mediating the cooperativity. We find that the presence of the first nucleotide
      prolongs the binding of the second nucleotide to Hsp90. In addition, we observe
      changes in the kinetics for both the open and the closed conformation of Hsp90 in
      dependence on the number of occupied nucleotide binding sites. Our analysis also
      reveals how the co-chaperone Aha1, known to accelerate Hsp90's ATPase activity,
      affects those transitions in a nucleotide-dependent and independent manner,
      thereby adding another layer of regulation to Hsp90.

PMID- 29045866
TI  - How Many Protein Sequences Fold to a Given Structure? A Coevolutionary Analysis.
AB  - Quantifying the relationship between protein sequence and structure is key to
      understanding the protein universe. A fundamental measure of this relationship is
      the total number of amino acid sequences that can fold to a target protein
      structure, known as the "sequence capacity," which has been suggested as a proxy
      for how designable a given protein fold is. Although sequence capacity has been
      extensively studied using lattice models and theory, numerical estimates for real
      protein structures are currently lacking. In this work, we have quantitatively
      estimated the sequence capacity of 10 proteins with a variety of different
      structures using a statistical model based on residue-residue co-evolution to
      capture the variation of sequences from the same protein family. Remarkably, we
      find that even for the smallest protein folds, such as the WW domain, the number
      of foldable sequences is extremely large, exceeding the Avogadro constant. In
      agreement with earlier theoretical work, the calculated sequence capacity is
      positively correlated with the size of the protein, or better, the density of
      contacts. This allows the absolute sequence capacity of a given protein to be
      approximately predicted from its structure. On the other hand, the relative
      sequence capacity, i.e., normalized by the total number of possible sequences, is
      an extremely tiny number and is strongly anti-correlated with the protein length.
      Thus, although there may be more foldable sequences for larger proteins, it will
      be much harder to find them. Lastly, we have correlated the evolutionary age of
      proteins in the CATH database with their sequence capacity as predicted by our
      model. The results suggest a trade-off between the opposing requirements of high
      designability and the likelihood of a novel fold emerging by chance.

PMID- 29045867
TI  - Enzyme-Triggered Dissociation of a FRET-Based Protein Biosensor Monitored by
      Synchrotron SAXS.
AB  - Protein biosensors are widely used for the monitoring of metabolite concentration
      and enzymatic activities inside living cells and in in vitro applications.
      Neutrophil elastase (NE) is a serine protease of relevance in inflammatory
      diseases whose activity can lead to pathological conditions if unregulated. This
      study focuses on the structural characterization of a biosensor for NE activity
      based on Forster resonance energy transfer (FRET). The cleavage by NE results in
      dissociation of the FRET fluorescent protein pair and alteration of the
      fluorescent emission spectrum. We have used small angle x-ray scattering at a
      high intensity synchrotron source, combined with model-free analysis of the
      scattering data, to demonstrate the structure of the biosensor and the effect of
      its exposure to NE on size and shape. These investigations, together with
      biochemical studies, established the nanostructure-activity relationship that may
      contribute to the detailed understanding of the FRET-based biosensor and guide
      the rational design of new biosensor constructs.

PMID- 29045868
TI  - Identification and Characterization of an Inside-Out Folding Intermediate of T4
      Phage Sliding Clamp.
AB  - Protein folding process involves formation of transiently occurring intermediates
      that are difficult to isolate and characterize. It is both necessary and
      interesting to characterize the structural conformations adopted by these
      intermediates, also called molten globules (MG), to understand protein folding.
      Here, we investigated the equilibrium (un)folding intermediate state of T4 phage
      gene product 45 (gp45, also known as DNA polymerase processivity factor or
      sliding clamp) obtained during chemical denaturation. We show that gp45 undergoes
      substantial conformational rearrangement during unfolding and forms an expanded
      dry-MG. By monitoring the fluorescence of tryptophans that were strategically
      introduced at various sites, we demonstrate that the urea-treated molecule has
      its surface residues flip inside the core, and closely placed residues move
      farther. We were also able to isolate and purify the MG form of gp45 in native
      condition (i.e., nondenaturing buffer, at physiological pH and temperature);
      characteristics of this purified molecule substantially match with urea-treated
      wild-type gp45. To the best of our knowledge, this is one of the few reports that
      demonstrate the isolation and purification of a protein folding intermediate in
      native condition. We believe that our work not only allows us to dissect the
      process of protein folding, but will also help in the designing of folding
      inhibitors against sliding clamps to treat a wide variety of diseases from
      bacterial infection to cancer, due to the vast presence of clamps in all the
      domains of life.

PMID- 29045869
TI  - Metastability Gap in the Phase Diagram of Monoclonal IgG Antibody.
AB  - Crystallization of IgG antibodies has important applications in the fields of
      structural biology, biotechnology, and biopharmaceutics. However, a rational
      approach to crystallize antibodies is still lacking. In this work, we report a
      method to estimate the solubility of antibodies at various temperatures. We
      experimentally determined the full phase diagram of an IgG antibody. Using the
      full diagram, we examined the metastability gaps, i.e., the distance between the
      crystal solubility line and the liquid-liquid coexistence curve, of IgG
      antibodies. By comparing our results to the partial phase diagrams of other IgGs
      reported in literature, we found that IgG antibodies have similar metastability
      gaps. Thereby, we present an equation with two phenomenological parameters to
      predict the approximate location of the solubility line of IgG antibodies with
      respect to their liquid-liquid coexistence curves. We have previously shown that
      the coexistence curve of an antibody solution can be readily determined by the
      polyethylene glycol-induced liquid-liquid phase separation method. Combining the
      polyethylene glycol-induced liquid-liquid phase separation measurements and the
      phenomenological equation in this article, we provide a general and practical
      means to predict the thermodynamic conditions for crystallizing IgG antibodies in
      the solution environments of interest.

PMID- 29045870
TI  - Exchange of Gramicidin between Lipid Bilayers: Implications for the Mechanism of
      Channel Formation.
AB  - The canonical mechanism of gramicidin (gA) channel formation is transmembrane
      dimerization of nonconducting subunits that reside in opposite bilayer leaflets.
      The channels do not open and close; they appear and disappear due to subunit
      association and dissociation. Many different types of experiments support this
      monomer <-> dimer mechanism. Recently, however, this mechanism was challenged,
      based on experiments with lipid vesicle-incorporated gA under conditions where
      vesicle fusion could be controlled. In these experiments, sustained channel
      activity was observed long after fusion had been terminated, which led to the
      proposal that gA single-channel current transitions result from closed-open
      transitions in long-lived bilayer-spanning dimers. This proposal is at odds with
      40 years of experiments, but involves the key assumption that gA monomers do not
      exchange between bilayers. We tested the possibility of peptide exchange between
      bilayers using three different types of experiments. First, we demonstrated the
      exchange of gA between 1,2-dierucoyl-sn-glycero-3-phosphocholine (DC22:1PC) or
      1,2-dioleoyl-sn-glycero-3-phosphocholine (DC18:1PC) lipid vesicles using a
      fluorescence assay for gA channel activity. Second, we added gA-free DC22:1PC
      vesicles to both sides of planar DC18:1PC bilayers preincubated with gA, which
      reduced channel activity up to 10-fold. Third, we added gA-containing DC22:1PC
      vesicles to one or both sides of DC18:1PC planar bilayers, which produced much
      higher channel activity when the gA-containing vesicles were added to both sides
      of the bilayer, as compared to one side only. All three types of experiments show
      that gA subunits can exchange between lipid bilayers. The exchange of subunits
      between bilayers thus is firmly established, which becomes a crucial
      consideration with respect to the mechanism of channel formation.

PMID- 29045872
TI  - The Detection of Nanoscale Membrane Bending with Polarized Localization
      Microscopy.
AB  - The curvature of biological membranes at the nanometer scale is critically
      important for vesicle trafficking, organelle morphology, and disease propagation.
      The initiation of membrane bending occurs at a length scale that is irresolvable
      by most superresolution optical microscopy methods. Here, we report the
      development of polarized localization microscopy (PLM), a pointillist optical
      imaging technique for the detection of nanoscale membrane curvature in
      correlation with single-molecule dynamics and molecular sorting. PLM combines
      polarized total internal reflection fluorescence microscopy and single-molecule
      localization microscopy to reveal membrane orientation with subdiffraction
      limited resolution without reducing localization precision by point spread
      function manipulation. Membrane curvature detection with PLM requires fewer
      localization events to detect curvature than three-dimensional single-molecule
      localization microscopy (e.g., photoactivated localization microscopy or
      stochastic optical reconstruction microscopy), which enables curvature detection
      10* faster via PLM. With rotationally confined lipophilic fluorophores and the
      polarized incident fluorescence excitation, membrane-bending events are revealed
      with superresolution. Engineered hemispherical membrane curvature with a radius
      >=24 nm was detected with PLM, and individual fluorophore localization precision
      was 13 +/- 5 nm. Further, deciphering molecular mobility as a function of
      membrane topology was enabled. The diffusion coefficient of individual DiI
      molecules was 25 +/- 5* higher in planar supported lipid bilayers than within
      nanoscale membrane curvature. Through the theoretical foundation and experimental
      demonstration provided here, PLM is poised to become a powerful technique for
      revealing the underlying biophysical mechanisms of membrane bending at
      physiological length scales.

PMID- 29045871
TI  - Mapping Cell Membrane Fluctuations Reveals Their Active Regulation and Transient
      Heterogeneities.
AB  - Shape fluctuations of the plasma membrane occur in all cells, are incessant, and
      are proposed to affect membrane functioning. Although studies show how membrane
      fluctuations are affected by cellular activity in adherent cells, their spatial
      regulation and the corresponding change in membrane mechanics remain unclear. In
      this article, we study how ATP-driven activities and actomyosin cytoskeleton
      impact basal membrane fluctuations in adherent cells. Using interference imaging,
      we map height fluctuations within single cells and compare the temporal spectra
      with existing theoretical models to gain insights about the underlying membrane
      mechanics. We find that ATP-dependent activities enhance the nanoscale z
      fluctuations but stretch out the membrane laterally. Although actin
      polymerization or myosin-II activity individually enhances fluctuations, the
      cortex in unperturbed cells stretches out the membrane and dampens fluctuations.
      Fitting with models suggest this dampening to be due to confinement by the
      cortex. However, reduced fluctuations on mitosis or on ATP
      depletion/stabilization of cortex correlate with increased tension. Both maps of
      fluctuations and local temporal autocorrelation functions reveal ATP-dependent
      transient short-range (<2 MUm) heterogeneities. Together, our results show how
      various ATP-driven processes differently affect membrane mechanics and hence
      fluctuations, while creating distinct local environments whose functional role
      needs future investigation.

PMID- 29045873
TI  - Nanoscale Membrane Budding Induced by CTxB and Detected via Polarized
      Localization Microscopy.
AB  - For endocytosis and exocytosis, membranes transition among planar, budding, and
      vesicular topographies through nanoscale reorganization of lipids, proteins, and
      carbohydrates. However, prior attempts to understand the initial stages of
      nanoscale bending have been limited by experimental resolution. Through the
      implementation of polarized localization microscopy, this article reports the
      inherent membrane bending capability of cholera toxin subunit B (CTxB) in quasi
      one-component-supported lipid bilayers. Membrane buds were first detected with
      <50 nm radius, grew to >200 nm radius, and extended into longer tubules with
      dependence on the membrane tension and CTxB concentration. Compared to the
      concentration of the planar-supported lipid bilayers, CTxB was (12 +/- 4)* more
      concentrated on the positive curvature top and (26 +/- 11)* more concentrated on
      the negative Gaussian curvature neck of the nanoscale membrane buds. CTxB is
      frequently used as a marker for liquid-ordered lipid phases; however, the
      coupling between CTxB and membrane bending provides an alternate understanding of
      CTxB-induced membrane reorganization. These findings allow for the
      reinterpretation of prior observations by correlating CTxB clustering and
      diffusion to CTxB-induced membrane bending. Single-particle tracking was
      performed on single lipids and CTxB to reveal the correlations among single
      molecule diffusion, CTxB accumulation, and membrane topography. Slowed lipid and
      CTxB diffusion was observed at the nanoscale bud locations, suggesting a local
      increase in the effective membrane viscosity or molecular crowding upon membrane
      bending. These results suggest inherent CTxB-induced membrane bending as a
      mechanism for initiating CTxB internalization in cells that could be independent
      of clathrin, caveolin, actin, and lipid phase separation.

PMID- 29045875
TI  - The Effect of Solutes on the Temperature of Miscibility Transitions in
      Multicomponent Membranes.
AB  - We address questions posed by experiments that show small-chain alcohols reduce
      the miscibility transition temperature when added to giant plasma membrane
      vesicles (GPMVs), but increase that temperature when added to giant unilamellar
      vesicles. In giant unilamellar vesicles the change in temperature displays a
      definite minimum, between decanol and tetradecanol, as a function of alcohol
      chain length; in GPMVs there is no such minimum. To emphasize the competition
      between internal entropies of the components and the interactions between them,
      we model the system as consisting of three different linear polymers. Two of them
      are the constituents of a liquid, one that can undergo a miscibility transition.
      To this liquid is added the third polymer component, which represents the short
      chain alcohol. We show that, within Flory-Huggins theory, the addition of alcohol
      causes an increase or decrease of the miscibility transition temperature
      depending upon the competition of two effects. The first is the dilution of the
      interactions between the two components of the liquid caused by the introduction
      of the alcohol. This tends to lower the transition temperature. The second effect
      is the preferential partitioning of the alcohol into one phase of the liquid or
      the other. This tends to raise the transition temperature irrespective of which
      phase the alcohol prefers. This second effect is the smallest, and the decrease
      in transition temperature the largest, when the alcohol partitions equally
      between the two phases. Such equal partitioning occurs when the effect of the
      entropic excluded volume interactions (which cause the alcohol to prefer one
      phase) just balances the effect of the direct interactions, which cause it to
      prefer the other. These results allow us to make several predictions, and to
      propose an explanation for the different behavior of the transition temperature
      in GPMVs and giant unilamellar vesicles that results from the addition of
      alcohols.

PMID- 29045874
TI  - Dynamic Scaling Analysis of Molecular Motion within the LAT:Grb2:SOS Protein
      Network on Membranes.
AB  - Biochemical signaling pathways often involve proteins with multiple, modular
      interaction domains. Signaling activates binding sites, such as by tyrosine
      phosphorylation, which enables protein recruitment and growth of networked
      protein assemblies. Although widely observed, the physical properties of the
      assemblies, as well as the mechanisms by which they function, remain largely
      unknown. Here we examine molecular mobility within LAT:Grb2:SOS assemblies on
      supported membranes by single-molecule tracking. Trajectory analysis reveals a
      discrete temporal transition to subdiffusive motion below a characteristic
      timescale, indicating that the LAT:Grb2:SOS assembly has the dynamical structure
      of a loosely entangled polymer. Such dynamical analysis is also applicable in
      living cells, where it offers another dimension on the characteristics of
      cellular signaling assemblies.

PMID- 29045876
TI  - Elastic Properties of Pore-Spanning Apical Cell Membranes Derived from MDCK II
      Cells.
AB  - The mechanical response of adherent, polarized cells to indentation is frequently
      attributed to the presence of an endogenous actin cortex attached to the inner
      leaflet of the plasma membrane. Here, we scrutinized the elastic properties of
      apical membranes separated from living cells and attached to a porous mesh in the
      absence of intracellular factors originating from the cytosol, organelles, the
      substrate, neighbors, and the nucleus. We found that a tension-based model
      describes the data very well providing essentially the prestress of the shell
      generated by adhesion of the apical membrane patches to the pore rim and the
      apparent area compressibility modulus, an intrinsic elastic modulus modulated by
      the surface excess stored in membrane reservoirs. Removal of membrane-associated
      proteins by proteases decreases the area compressibility modulus, whereas
      fixation and cross-linking of proteins with glutaraldehyde increases it.

PMID- 29045877
TI  - Self-Organization of FtsZ Polymers in Solution Reveals Spacer Role of the
      Disordered C-Terminal Tail.
AB  - FtsZ is a self-assembling GTPase that forms, below the inner membrane, the mid
      cell Z-ring guiding bacterial division. FtsZ monomers polymerize head to tail
      forming tubulin-like dynamic protofilaments, whose organization in the Z-ring is
      an unresolved problem. Rather than forming a well-defined structure, FtsZ
      protofilaments laterally associate in vitro into polymorphic condensates
      typically imaged on surfaces. We describe here nanoscale self-organizing
      properties of FtsZ assemblies in solution that underlie Z-ring assembly,
      employing time-resolved x-ray scattering and cryo-electron microscopy. We find
      that FtsZ forms bundles made of loosely bound filaments of variable length and
      curvature. Individual FtsZ protofilaments further bend upon nucleotide
      hydrolysis, highlighted by the observation of some large circular structures with
      2.5-5 degrees  curvature angles between subunits, followed by disassembly end
      products consisting of highly curved oligomers and 16-subunit -220 A diameter
      mini-rings, here observed by cryo-electron microscopy. Neighbor FtsZ filaments in
      bundles are laterally spaced 70 A, leaving a gap in between. In contrast, close
      contact between filament core structures (~50 A spacing) is observed in straight
      polymers of FtsZ constructs lacking the C-terminal tail, which is known to
      provide a flexible tether essential for FtsZ functions in cell division. Changing
      the length of the intrinsically disordered C-tail linker modifies the
      interfilament spacing. We propose that the linker prevents dynamic FtsZ
      protofilaments in bundles from sticking to one another, holding them apart at a
      distance similar to the lateral spacing observed by electron cryotomography in
      several bacteria and liposomes. According to this model, weak interactions
      between curved polar FtsZ protofilaments through their the C-tails may facilitate
      the coherent treadmilling dynamics of membrane-associated FtsZ bundles in
      reconstituted systems, as well as the recently discovered movement of FtsZ
      clusters around bacterial Z-rings that is powered by GTP hydrolysis and guides
      correct septal cell wall synthesis and cell division.

PMID- 29045878
TI  - Homodimeric Kinesin-2 KIF3CC Promotes Microtubule Dynamics.
AB  - KIF3C is one subunit of the functional microtubule-based kinesin-2 KIF3AC motor,
      an anterograde cargo transporter in neurons. However, KIF3C has also been
      implicated as an injury-specific kinesin that is a key regulator of axonal growth
      and regeneration by promoting microtubule dynamics for reorganization at the
      neuronal growth cone. To test its potential role as a modulator of microtubule
      dynamics in vitro, an engineered homodimeric KIF3CC was incorporated into a
      dynamic microtubule assay and examined by total internal reflection fluorescence
      microscopy. The results reveal that KIF3CC is targeted to the microtubule plus
      end, acts as a potent catastrophe factor through an increase in microtubule
      catastrophe frequency, and does so by elimination of the dependence of the
      catastrophe rate on microtubule lifetime. Moreover, KIF3CC accelerates the
      catastrophe rate without altering the microtubule growth rate. Therefore, the ATP
      promoted KIF3CC mechanism of catastrophe is different from the well-described
      catastrophe factors kinesin-13 MCAK and kinesin-8 Kip3/KIF18A. The properties of
      KIF3CC were not shared by heterodimeric KIF3AC and required the unique KIF3C
      specific sequence extension in loop L11 at the microtubule interface. At the
      microtubule plus-end, the presence of KIF3CC resulted in modulation of the
      tapered structure typically seen in growing dynamic microtubules to microtubule
      blunt plus-ends. Overall our results implicate homodimeric KIF3CC as a unique
      promoter of microtubule catastrophe and substantiate its physiological role in
      cytoskeletal remodeling.

PMID- 29045879
TI  - Probing Cell Adhesion Profiles with a Microscale Adhesive Choice Assay.
AB  - In this work, we introduce, to our knowledge, a new set of adhesion-based
      biomarkers for characterizing mammalian cells. Mammalian cell adhesion to the
      extracellular matrix influences numerous physiological processes. Current in
      vitro methods to probe adhesion focus on adhesive force to a single surface,
      which can investigate only a subcomponent of the adhesive, motility, and
      polarization cues responsible for adhesion in the 3D tissue environment. Here, we
      demonstrate a method to quantify the transhesive properties of cells that relies
      on the microscale juxtaposition of two extracellular matrix-coated surfaces. By
      multiplexing this approach, we investigate the unique transhesive profiles for
      breast cancer cells that are adapted to colonize different metastatic sites. We
      find that malignant breast cancer cells readily transfer to new collagen I
      surfaces, and away from basement membrane proteins. Integrins and actin
      polymerization largely regulate this transfer. This tool can be readily adopted
      in cell biology and cancer research to uncover, to our knowledge, novel drivers
      of adhesion (or de-adhesion) and sort cell populations based on complex
      phenotypes with physiological relevance.

PMID- 29045881
TI  - Confocal Rheology Probes the Structure and Mechanics of Collagen through the Sol
      Gel Transition.
AB  - Fibrillar type I collagen-based hydrogels are commonly used in tissue engineering
      and as matrices for biophysical studies. Mechanical and structural properties of
      these gels are known to be governed by the conditions under which fibrillogenesis
      occurs, exhibiting variation as a function of protein concentration, temperature,
      pH, and ionic strength. Deeper understanding of how macroscopic structure affects
      viscoelastic properties of collagen gels over the course of fibrillogenesis
      provides fundamental insight into biopolymer gel properties and promises enhanced
      control over the properties of such gels. Here, we investigate type I collagen
      fibrillogenesis using confocal rheology-simultaneous confocal reflectance
      microscopy, confocal fluorescence microscopy, and rheology. The multimodal
      approach allows direct comparison of how viscoelastic properties track the
      structural evolution of the gel on fiber and network length scales. Quantitative
      assessment and comparison of each imaging modality and the simultaneously
      collected rheological measurements show that the presence of a system-spanning
      structure occurs at a time similar to rheological determinants of gelation.
      Although this and some rheological measures are consistent with critical gelation
      through percolation, additional rheological and structural properties of the gel
      are found to be inconsistent with this theory. This study clarifies how structure
      sets viscoelasticity during collagen fibrillogenesis and more broadly highlights
      the utility of multimodal measurements as critical test-beds for theoretical
      descriptions of complex systems.

PMID- 29045880
TI  - A Model for Link Pruning to Establish Correctly Polarized and Oriented Tip Links
      in Hair Bundles.
AB  - Tip links are thought to gate the mechanically sensitive transduction channels of
      hair cells, but how they form during development and regeneration remains
      mysterious. In particular, it is unclear how tip links are strung between
      stereocilia so that they are oriented parallel to a single axis; why their
      polarity is uniform despite their constituent molecules' intrinsic asymmetry; and
      why only a single tip link is present at each tip-link position. We present here
      a series of simple rules that reasonably explain why these phenomena occur. In
      particular, our model relies on each of the two ends of the tip link having
      distinct Ca2+-dependent stability and being connected to different motor
      complexes. A simulation employing these rules allowed us to explore the parameter
      space for the model, demonstrating the importance of the feedback between
      transduction channels and angled links, links that are 60 degrees  off-axis with
      respect to mature tip links. We tested this key aspect of the model by examining
      angled links in chick cochlea hair cells. As implied by the assumptions used to
      generate the model, we found that angled links were stabilized if there was no
      tip link at the tip of the upper stereocilium, and appeared when transduction
      channels were blocked. The model thus plausibly explains how tip-link formation
      and pruning can occur.

PMID- 29045882
TI  - Untangling the Hairball: Fitness-Based Asymptotic Reduction of Biological
      Networks.
AB  - Complex mathematical models of interaction networks are routinely used for
      prediction in systems biology. However, it is difficult to reconcile network
      complexities with a formal understanding of their behavior. Here, we propose a
      simple procedure (called phi-) to reduce biological models to functional
      submodules, using statistical mechanics of complex systems combined with a
      fitness-based approach inspired by in silico evolution. The phi- algorithm works
      by putting parameters or combination of parameters to some asymptotic limit,
      while keeping (or slightly improving) the model performance, and requires
      parameter symmetry breaking for more complex models. We illustrate phi- on
      biochemical adaptation and on different models of immune recognition by T cells.
      An intractable model of immune recognition with close to a hundred individual
      transition rates is reduced to a simple two-parameter model. The phi- algorithm
      extracts three different mechanisms for early immune recognition, and
      automatically discovers similar functional modules in different models of the
      same process, allowing for model classification and comparison. Our procedure can
      be applied to biological networks based on rate equations using a fitness
      function that quantifies phenotypic performance.

PMID- 29045883
TI  - In Vitro-In Vivo Correlations of Carbamazepine Nanodispersions for Application in
      Formulation Development.
AB  - During formulation development, efficiently integrating in vitro dissolution
      testing can significantly improve one's ability to estimate in vivo performance
      and aide in the selection of premier drug candidates. The concept of in vitro-in
      vivo relationship/correlation has garnered significant attention from
      pharmaceutical scientists to predict expected bioavailability characteristics for
      drug substances and products. The present work illustrates a comparative
      evaluation of in vitro tests to access crystalline carbamazepine and various
      types of amorphous and crystalline dispersions of carbamazepine and Eudragit(r)
      L100 produced by spray drying, including a membrane-permeation dissolution
      methodology and nonsink dissolution. To establish the best model, parameters such
      as pH, membrane constitution, and dissolution media composition were
      investigated. The in vitro results were compared against in vivo mice
      pharmacokinetic studies and qualitatively, the membrane-permeation dissolution
      methodology correlated well with in vivo. Various correlations were performed in
      order to evaluate the optimal model for characterizing the relationship. Results
      exhibited a coefficient of determination (R2) values of 0.90 and 1.00, depicting
      a linear relationship of the data in comparison. Therefore, for the current
      formulation system (drug/polymer/technique), membrane-permeation dissolution can
      guide formulation development and potentially reduce the number of animal and
      clinical pharmacokinetic studies required.

PMID- 29045884
TI  - Effect of Phosphate Ion on the Structure of Lumazine Synthase, an Antigen
      Presentation System From Bacillus anthracis.
AB  - Lumazine synthase (LS) is an oligomeric enzyme involved in the biosynthesis of
      riboflavin in microorganisms, fungi, and plants. LS has become of significant
      interest to biomedical science because of its critical biological role and
      attractive structural properties for antigen presentation in vaccines. LS derived
      from Bacillus anthracis (BaLS) consists of 60 identical subunits forming an
      icosahedron. Its crystal structure has been solved, but its dynamic
      conformational properties have not yet been studied. We investigated the
      conformation of BaLS in response to different stress conditions (e.g., chemical
      denaturants, pH, and temperature) using a variety of biophysical techniques. The
      physical basis for these thermal transitions was studied, indicating that a
      molten globular state was present during chemical unfolding by guanidine HCl. In
      addition, BaLS showed 2 distinct thermal transitions in phosphate-containing
      buffers. The first transition was due to the dissociation of phosphate ions from
      BaLS and the second one came from the dissociation and conformational alteration
      of its icosahedral structure. A small conformational alteration was induced by
      the binding/dissociation of phosphate ions to BaLS. This work provides a closer
      view of the conformational behavior of BaLS and provides important information
      for the formulation of vaccines which use this protein.

PMID- 29045886
TI  - Poly(amidoamine) Dendrimers as a Pharmaceutical Excipient. Are We There yet?
AB  - Drug solubility could affect the therapeutic use of a drug because the biological
      activity of a drug is only possible if some fraction of a dissolved drug can
      permeate and overcome biological membranes to reach its site of action. The
      solubility-permeation interplay is therefore, probably the most important factor
      in determining a successful therapeutic outcome of any drug because more than 40%
      of marketed drugs and more than 70% of pipeline drugs show poor water solubility.
      Several solubilization techniques are used and include, balancing of pH-pKa
      properties, employment of cosolvents, and the solubilization by host-guest
      carriers. A relatively new addition to the polymer plethora of solubilizers are
      the poly(amidoamine) dendrimers. These highly branched, "tree-like" nanocarriers
      have a significant solubilization capacity for drugs in their cavities and also
      potentially via their terminals. Despite their successful solubilization
      capability, they are still plagued by some undesired properties such as
      cytotoxicity. Poly(amidoamine) however, seems to be a very lucrative target to
      develop into a pharmaceutical excipient, which will ultimately be confirmed by an
      official pharmacopeial monograph.

PMID- 29045887
TI  - Polymorphism, Intermolecular Interactions, and Spectroscopic Properties in
      Crystal Structures of Sulfonamides.
AB  - The antibiotics family of sulfonamides has been used worldwide intensively in
      human therapeutics and farm livestock during decades. Intermolecular interactions
      of these sulfamides are important to understand their bioactivity and
      biodegradation. These interactions are also responsible for their supramolecular
      structures. The intermolecular interactions in the crystal polymorphs of the
      sulfonamides, sulfamethoxypyridazine, and sulfamethoxydiazine, as models of
      sulfonamides, have been studied by using quantum mechanical calculations.
      Different conformations in the sulphonamide molecules have been detected in the
      crystal polymorphs. Several intermolecular patterns have been studied to
      understand the molecular packing behavior in these antibiotics. Strong
      intermolecular hydrogen bonds and pi-pi interactions are the main driving forces
      for crystal packing in these sulfonamides. Different stability between polymorphs
      can explain the experimental behavior of these crystal forms. The calculated
      infrared spectroscopy frequencies explain the main intermolecular interactions in
      these crystals.

PMID- 29045888
TI  - To plan or not to plan: Does planning for production remove facilitation from
      associative priming?
AB  - Theories of conversation propose that in order to have smooth transitions from
      one turn to the next, speakers already plan their response while listening to
      their interlocutor. Moreover, it has been argued that speakers align their
      linguistic representations (i.e. prime each other), thereby reducing the
      processing costs associated with concurrent listening and speaking. In two
      experiments, we assessed how identity and associative priming from spoken words
      onto picture naming were affected by a concurrent speech planning task. In a
      baseline (no name) condition, participants heard prime words that were identical,
      associatively related, or unrelated to target pictures presented two seconds
      after prime onset. Each prime was accompanied by a non-target picture and
      followed by its recorded name. The participant did not name the non-target
      picture. In the plan condition, the participants first named the non-target
      picture, instead of listening to the recording, and then the target. In
      Experiment 1, where the plan- and no-plan conditions were tested between
      participants, priming effects of equal strength were found in the plan and no
      plan condition. In Experiment 2, where the two conditions were tested within
      participants, the identity priming effect was maintained, but the associative
      priming effect was only seen in the no-plan but not in the plan condition. In
      this experiment, participant had to decide at the onset of each trial whether or
      not to name the non-target picture, rendering the task more complex than in
      Experiment 1. These decision processes may have interfered with the processing of
      the primes. Thus, associative priming can take place during speech planning, but
      only if the cognitive load is not too high.

PMID- 29045885
TI  - Fabrication and Use of Poly(d,l-lactide-co-glycolide)-Based Formulations Designed
      for Modified Release of 5-Fluorouracil.
AB  - 5-fluorouracil (5-FU) is a chemotherapeutic agent that has been used for the
      treatment of a variety of malignancies since its initial introduction to the
      clinic in 1957. Owing to its short biological half-life, multiple dosings are
      generally required to maintain effective 5-FU plasma concentrations throughout
      the therapeutic period. Clinical studies have shown that continuous 5-FU
      administration is generally superior to bolus injection as exhibited by lower
      toxicities and increased therapeutic efficacy. Optimal therapeutic efficacy,
      however, is often compromised by the limiting therapeutic index. Whilst oral
      formulations are also used, these suffer from the drawbacks of variable
      bioavailability and first-pass metabolism. As a result, sustained release
      formulations of 5-FU have been investigated in an effort to mimic the kinetics of
      continuous infusion particularly for situations where local delivery is
      considered appropriate. The biocompatible, biodegradable, and highly tunable
      synthetic polymer, poly(d,l-lactide-co-glycolide) (PLGA), is widely used as a
      vector for sustained drug delivery, however, issues such as insufficient loading
      and inappropriate burst release kinetics have dogged progress into the clinic for
      small hydrophilic drugs such as 5-FU. This review provides introductory
      information about the mechanism of action, pharmacokinetic and physicochemical
      properties, and clinical use of 5-FU that have contributed to the development of
      PLGA-based 5-FU release platforms. In addition, this review provides information
      on fabrication methods used for a range of 5-FU-loaded PLGA formulations and
      discusses factors affecting the release kinetics of 5-FU as well as the in vitro
      and in vivo antitumor or antiproliferative efficacy of these platforms.

PMID- 29045890
TI  - A RHIM with a View: FLYing with Functional Amyloids.
AB  - Recognition of bacterial peptidoglycan by the Drosophila IMD pathway triggers NF
      kappaB activation and an associated immune response. In this issue of Immunity,
      Kleino et al. (2017) show that proteins in the IMD pathway form functional
      amyloids via a cryptic motif resembling the RHIM motif found in mammalian RIPK
      proteins. Amyloid formation can be negatively regulated, suggesting that it
      presents a regulatory point in multiple biological processes.

PMID- 29045889
TI  - The Pathway to a Universal Influenza Vaccine.
AB  - Development of a universal influenza vaccine is a research priority for the
      National Institute of Allergy and Infectious Diseases (NIAID) at the National
      Institutes of Health. To facilitate this goal, we convened a workshop in
      Rockville, Maryland to identify knowledge gaps in influenza research and develop
      strategies to fill them.

PMID- 29045891
TI  - CD14-New Tricks of an Old Acquaintance.
AB  - Zanoni et al. (2017) show that the LPS receptor CD14 promotes internalization of
      oxidized phospholipids, a hallmark of dying cells, triggering hyperactivation of
      dendritic cells and macrophages. Their findings reveal CD14 as a regulator of
      responses to infection and damage, relaying context-dependent signals that
      determine inflammatory cell fate decisions.

PMID- 29045892
TI  - Wait, Wait ... OK Now Go In: iNKT Cells Resolve Liver Inflammation.
AB  - Resolution of inflammation is pivotal to restoring tissue homeostasis, yet there
      is limited understanding of how this process is regulated. In this issue of
      Immunity, Liew et al. (2017) reveal a critical role for invariant natural killer
      T (iNKT) cells in switching inflammation to tissue repair in an interlukin-4
      dependent process.

PMID- 29045893
TI  - HIV-1 Latency by Transition.
AB  - The latent HIV-1 reservoir represents the major barrier for the development of an
      HIV-1 cure. In this issue of Immunity, Shan et al. (2017) highlight that effector
      to-memory transitioning (EMT) CD4+ T cells are particularly permissive for the
      establishment of latent HIV-1 infection.

PMID- 29045894
TI  - From Oncogene Interference to Neutrophil Immune Modulation.
AB  - Oncogenes can aid tumor progression in a cancer cell-extrinsic way. In this issue
      of Immunity, Glodde et al. (2017) demonstrate that interference with c-MET
      tyrosine kinase receptor can relieve neutrophil-dependent immune suppression and
      unleash the effectiveness of immunotherapy even in the context of c-MET
      independent tumors.

PMID- 29045895
TI  - cGAS Micro-Manages Genotoxic Stress.
AB  - Maintenance of genome integrity is essential to prevent cancer. Genotoxic stress
      drives damaged DNA out of the nucleus by forming micronuclei. Two studies in
      Nature reveal how the cytosolic DNA sensor cGAS gains access to the cargo within
      micronuclei to drive type I IFN responses.

PMID- 29045896
TI  - Microbes REV up Host Metabolism around the Clock.
AB  - There is increasing evidence that the microbiome regulates host metabolism, but
      specific mechanisms underlying these interactions remain poorly understood. In a
      recent paper in Science, Wang et al. (2017) reveal that the gut microbiota
      regulates the expression of circadian-clock genes to impact host lipid metabolism
      and body composition.

PMID- 29045897
TI  - Monocyte-Macrophages and T Cells in Atherosclerosis.
AB  - Atherosclerosis is an arterial disease process characterized by the focal
      subendothelial accumulation of apolipoprotein-B-containing lipoproteins, immune
      and vascular wall cells, and extracellular matrix. The lipoproteins acquire
      features of damage-associated molecular patterns and trigger first an innate
      immune response, dominated by monocyte-macrophages, and then an adaptive immune
      response. These inflammatory responses often become chronic and non-resolving and
      can lead to arterial damage and thrombosis-induced organ infarction. The innate
      immune response is regulated at various stages, from hematopoiesis to monocyte
      changes and macrophage activation. The adaptive immune response is regulated
      primarily by mechanisms that affect the balance between regulatory and effector T
      cells. Mechanisms related to cellular cholesterol, phenotypic plasticity,
      metabolism, and aging play key roles in affecting these responses. Herein, we
      review select topics that shed light on these processes and suggest new treatment
      strategies.

PMID- 29045898
TI  - Peptidoglycan-Sensing Receptors Trigger the Formation of Functional Amyloids of
      the Adaptor Protein Imd to Initiate Drosophila NF-kappaB Signaling.
AB  - In the Drosophila immune response, bacterial derived diaminopimelic acid-type
      peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction
      with the adaptor protein Imd leads to activation of the NF-kappaB homolog Relish
      and robust antimicrobial peptide gene expression. PGRP-LC, PGRP-LE, and Imd each
      contain a motif with some resemblance to the RIP Homotypic Interaction Motif
      (RHIM), a domain found in mammalian RIPK proteins forming functional amyloids
      during necroptosis. Here we found that despite sequence divergence, these
      Drosophila cryptic RHIMs formed amyloid fibrils in vitro and in cells. Amyloid
      formation was required for signaling downstream of Imd, and in contrast to the
      mammalian RHIMs, was not associated with cell death. Furthermore, amyloid
      formation constituted a regulatable step and could be inhibited by Pirk, an
      endogenous feedback regulator of this pathway. Thus, diverse sequence motifs are
      capable of forming amyloidal signaling platforms, and the formation of these
      platforms may present a regulatory point in multiple biological processes.

PMID- 29045899
TI  - Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells
      in Chronic versus Acute Infection.
AB  - Distinct molecular pathways govern the differentiation of CD8+ effector T cells
      into memory or exhausted T cells during acute and chronic viral infection, but
      these are not well studied in humans. Here, we employed an integrative systems
      immunology approach to identify transcriptional commonalities and differences
      between virus-specific CD8+ T cells from patients with persistent and
      spontaneously resolving hepatitis C virus (HCV) infection during the acute phase.
      We observed dysregulation of metabolic processes during early persistent
      infection that was linked to changes in expression of genes related to
      nucleosomal regulation of transcription, T cell differentiation, and the
      inflammatory response and correlated with subject age, sex, and the presence of
      HCV-specific CD4+ T cell populations. These early changes in HCV-specific CD8+ T
      cell transcription preceded the overt establishment of T cell exhaustion, making
      this signature a prime target in the search for the regulatory origins of T cell
      dysfunction in chronic viral infection.

PMID- 29045900
TI  - Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals
      a Bipartite Architecture of Human Lymphopoiesis.
AB  - The classical model of hematopoiesis established in the mouse postulates that
      lymphoid cells originate from a founder population of common lymphoid
      progenitors. Here, using a modeling approach in humanized mice, we showed that
      human lymphoid development stemmed from distinct populations of CD127- and CD127+
      early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and
      in vivo functional assays, we demonstrated that CD127- and CD127+ ELPs emerged
      independently from lympho-mono-dendritic progenitors, responded differently to
      Notch1 signals, underwent divergent modes of lineage restriction, and displayed
      both common and specific differentiation potentials. Whereas CD127- ELPs
      comprised precursors of T cells, marginal zone B cells, and natural killer (NK)
      and innate lymphoid cells (ILCs), CD127+ ELPs supported production of all NK
      cell, ILC, and B cell populations but lacked T potential. On the basis of these
      results, we propose a "two-family" model of human lymphoid development that
      differs from the prevailing model of hematopoiesis.

PMID- 29045901
TI  - By Capturing Inflammatory Lipids Released from Dying Cells, the Receptor CD14
      Induces Inflammasome-Dependent Phagocyte Hyperactivation.
AB  - A heterogeneous mixture of lipids called oxPAPC, derived from dying cells, can
      hyperactivate dendritic cells (DCs) but not macrophages. Hyperactive DCs are
      defined by their ability to release interleukin-1 (IL-1) while maintaining cell
      viability, endowing these cells with potent aptitude to stimulate adaptive
      immunity. Herein, we found that the bacterial lipopolysaccharide receptor CD14
      captured extracellular oxPAPC and delivered these lipids into the cell to promote
      inflammasome-dependent DC hyperactivation. Notably, we identified two specific
      components within the oxPAPC mixture that hyperactivated macrophages, allowing
      these cells to release IL-1 for several days, by a CD14-dependent process. In
      murine models of sepsis, conditions that promoted cell hyperactivation resulted
      in inflammation but not lethality. Thus, multiple phagocytes are capable of
      hyperactivation in response to oxPAPC, with CD14 acting as the earliest regulator
      in this process, serving to capture and transport these lipids to promote
      inflammatory cell fate decisions.

PMID- 29045902
TI  - Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to
      Function in a T Cell Receptor-Independent Fashion.
AB  - Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL
      33), which induces type-2 helper T cells (Th2 cells) at the site of infection to
      produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)
      independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13
      secretion, Th2 cells required the expression of the epidermal growth factor
      receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling
      complex between T1/ST2 (the IL-33R) and EGFR. This shared signaling complex
      allowed IL-33 to induce the EGFR-mediated activation of the MAP-kinase signaling
      pathway and consequently the expression of IL-13. Lack of EGFR expression on T
      cells abrogated IL-13 expression in infected tissues and impaired host
      resistance. EGFR expression on Th2 cells was TCR-signaling dependent, and
      therefore, our data reveal a mechanism by which antigen presentation controls the
      innate effector function of Th2 cells at the site of inflammation.

PMID- 29045903
TI  - HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.
AB  - Infection by helminth parasites is associated with amelioration of allergic
      reactivity, but mechanistic insights into this association are lacking. Products
      secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2
      (allergic) immune responses through interference in the interleukin-33 (IL-33)
      pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an
      IL-33-suppressive 26-kDa protein, containing three predicted complement control
      protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate
      lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen
      administration, and diminished eosinophilic responses to Nippostrongylus
      brasiliensis, increasing parasite burden. HpARI bound directly to both mouse and
      human IL-33 (in the cytokine's activated state) and also to nuclear DNA via its N
      terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells,
      preventing its release, and forestalling initiation of type 2 allergic responses.
      Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in
      both infection and allergy.

PMID- 29045904
TI  - iNKT Cells Orchestrate a Switch from Inflammation to Resolution of Sterile Liver
      Injury.
AB  - After traumatic injury, some cells function as detectors to sense injury and to
      modulate the local immune response toward a restitution phase by affecting the
      local cytokine milieu. Using intravital microscopy, we observed that patrolling
      invariant natural killer T (iNKT) cells were initially excluded from a site of
      hepatic injury but subsequently were strategically arrested first via self
      antigens and then by cytokines, circumscribing the injured site at exactly the
      location where monocytes co-localized and hepatocytes proliferated. Activation of
      iNKT cells by self-antigens resulted in the production of interleukin-4 (IL-4)
      but not interferon-gamma (IFN-gamma). This promoted increased hepatocyte
      proliferation, monocyte transition (from Ly6Chi to Ly6Clo), and improved healing
      where IL-4 from iNKT cells was critical for these processes. Disruption of any of
      these mechanisms led to delayed wound healing. We have shown that self-antigen
      driven iNKT cells function as sensors and orchestrators of the transformation
      from inflammation to tissue restitution for essential timely wound repair.

PMID- 29045905
TI  - Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T
      Cells Permissive for Latent HIV-1 Infection.
AB  - The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major
      barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on
      regulation of viral gene expression in cells in which latent infection is
      established. However, it remains unclear how infection initially becomes latent.
      Here we described a unique set of properties of CD4+ T cells undergoing effector
      to-memory transition including temporary upregulation of CCR5 expression and
      rapid downregulation of cellular gene transcription. These cells allowed
      completion of steps in the HIV-1 life cycle through integration but suppressed
      HIV-1 gene transcription, thus allowing the establishment of latency. CD4+ T
      cells in this stage were substantially more permissive for HIV-1 latent infection
      than other CD4+ T cells. Establishment of latent HIV-1 infection in CD4+ T could
      be inhibited by viral-specific CD8+ T cells, a result with implications for
      elimination of latent HIV-1 infection by T cell-based vaccines.

PMID- 29045908
TI  - Long-term exposure to residential railway and road traffic noise and risk for
      diabetes in a Danish cohort.
AB  - BACKGROUND: Road traffic noise exposure has been found associated with diabetes
      incidence. Evidence for an association between railway noise exposure is less
      clear, as large studies with detailed railway noise modelling are lacking.
      PURPOSE: To investigate the association between residential railway noise and
      diabetes incidence, and to repeat previous analyses on road traffic noise and
      diabetes with longer follow-up time. METHODS: Among 50,534 middle-aged Danes
      enrolled into the Diet, Cancer and Health cohort from 1993 to 97, we identified
      5062 cases of incident diabetes during a median follow-up of 15.5 years. Present
      and historical residential addresses from 1987 to 2012 were found in national
      registries, and railway and road traffic noise (Lden) were modelled for all
      addresses, using the Nordic prediction method. We used Cox proportional hazard
      models to investigate the association between residential traffic noise over 1
      and 5 years before diagnosis, and diabetes incidence. Hazard ratios (HRs) were
      calculated as crude and adjusted for potential confounders. RESULTS: We found no
      association between railway noise exposure and diabetes incidence among the 9527
      persons exposed, regardless of exposure time-window: HR 0.99 (0.94-1.04) per 10dB
      for 5-year exposure in fully adjusted models. There was no effect modification by
      sex, road traffic noise, and education. We confirmed the previously found
      association between road traffic noise exposure and diabetes including 6
      additional years of follow-up: HR 1.08 (1.04-1.13) per 10dB for 5-year exposure
      in fully adjusted models. CONCLUSION: The study does not suggest an association
      between residential railway noise exposure and diabetes incidence, but supports
      the finding of a direct association with residential road traffic noise.

PMID- 29045907
TI  - Reactive Neutrophil Responses Dependent on the Receptor Tyrosine Kinase c-MET
      Limit Cancer Immunotherapy.
AB  - Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic
      to target oncogenic signaling in tumor cells. We found that concomitant c-MET
      inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in
      murine cancer models by increasing effector T cell infiltration in tumors. This
      therapeutic effect was independent of tumor cell-intrinsic c-MET dependence.
      Mechanistically, c-MET inhibition impaired the reactive mobilization and
      recruitment of neutrophils into tumors and draining lymph nodes in response to
      cytotoxic immunotherapies. In the absence of c-MET inhibition, neutrophils
      recruited to T cell-inflamed microenvironments rapidly acquired immunosuppressive
      properties, restraining T cell expansion and effector functions. In cancer
      patients, high serum levels of the c-MET ligand HGF correlated with increasing
      neutrophil counts and poor responses to checkpoint blockade therapies. Our
      findings reveal a role for the HGF/c-MET pathway in neutrophil recruitment and
      function and suggest that c-MET inhibitor co-treatment may improve responses to
      cancer immunotherapy in settings beyond c-MET-dependent tumors.

PMID- 29045909
TI  - An integrative review of graduate transition programmes: Developmental
      considerations for nursing management.
AB  - : Graduate transition programmes have been developed to recruit new nursing staff
      and facilitate an effective transition from nursing student to Registered Nurse
      within the clinical environment. Therefore the aim of this paper was to explore
      the various elements included in nursing graduate transition programmes. An
      integrative review was undertaken incorporating a strict inclusion criterion,
      critical appraisal, and thematic analysis of 30 studies. There are numerous
      transition programmes available yet there remains a lack of transparency
      regarding their aims/objectives, course content, support timeframe and the type
      of support provided. This inconsistency has resulted in a lack of clarity
      regarding efficacy or superiority of any one programme over another. Innovative
      multifaceted programs may assist in supporting the graduate registered nurse to
      transition effectively into the clinical environment. Providing these support
      programmes may allow nurse managers to recruit new graduates and therefore
      decrease the staff budget expenditure. IMPLICATIONS FOR NURSING MANAGEMENT: No
      graduate programme was shown to be superior to others yet graduate programmes
      appear to positively influence the experience of the graduate and increase staff
      recruitment. Comparative research is needed to ascertain the integral components
      of these programmes.

PMID- 29045911
TI  - Fuzzy-Rough Cognitive Networks.
AB  - Rough Cognitive Networks (RCNs) are a kind of granular neural network that
      augments the reasoning rule present in Fuzzy Cognitive Maps with crisp
      information granules coming from Rough Set Theory. While RCNs have shown promise
      in solving different classification problems, this model is still very sensitive
      to the similarity threshold upon which the rough information granules are built.
      In this paper, we cast the RCN model within the framework of fuzzy rough sets in
      an attempt to eliminate the need for a user-specified similarity threshold while
      retaining the model's discriminatory power. As far as we know, this is the first
      study that brings fuzzy sets into the domain of rough cognitive mapping.
      Numerical results in the presence of 140 well-known pattern classification
      problems reveal that our approach, referred to as Fuzzy-Rough Cognitive Networks,
      is capable of outperforming most traditional classifiers used for benchmarking
      purposes. Furthermore, we explore the impact of using different heterogeneous
      distance functions and fuzzy operators over the performance of our granular
      neural network.

PMID- 29045906
TI  - CTLA-4+PD-1- Memory CD4+ T Cells Critically Contribute to Viral Persistence in
      Antiretroviral Therapy-Suppressed, SIV-Infected Rhesus Macaques.
AB  - Antiretroviral therapy (ART) suppresses viral replication in HIV-infected
      individuals but does not eliminate the reservoir of latently infected cells.
      Recent work identified PD-1+ follicular helper T (Tfh) cells as an important
      cellular compartment for viral persistence. Here, using ART-treated, SIV-infected
      rhesus macaques, we show that CTLA-4+PD-1- memory CD4+ T cells, which share
      phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood,
      lymph nodes (LN), spleen, and gut, and contained replication-competent and
      infectious virus. In contrast to PD-1+ Tfh cells, SIV-enriched CTLA-4+PD-1- CD4+
      T cells were found outside the B cell follicle of the LN, predicted the size of
      the persistent viral reservoir during ART, and significantly increased their
      contribution to the SIV reservoir with prolonged ART-mediated viral suppression.
      We have shown that CTLA-4+PD-1- memory CD4+ T cells are a previously unrecognized
      component of the SIV and HIV reservoir that should be therapeutically targeted
      for a functional HIV-1 cure.

PMID- 29045910
TI  - Immunogenicity and protective efficacy of multistage vaccine candidates (Mtb8.4
      HspX and HspX-Mtb8.4) against Mycobacterium tuberculosis infection in mice.
AB  - In this study, Mtb8.4 and HspX, which are expressed at proliferating and dormant
      stages of Mycobacterium tuberculosis (M. tuberculosis), respectively, were chosen
      to construct two fusion proteins, Mtb8.4-HspX (8.4H) and HspX-Mtb8.4 (H8.4), and
      we investigated whether the antigen dose and protein sequential order could
      impact the immunogenicity and protective efficacy of these fusion protein
      vaccines against M. tuberculosis. C57BL/6 mice were vaccinated with new
      constructions containing a fusion protein with adjuvant of N, N'-dimethyl-N, N'
      dioctadecylammonium bromide (DDA) or a mixed adjuvant composed of DDA,
      polyribocytidylic acid and gelatin (DPG), and the antigen specific immune
      responses and protective efficacy against M. tuberculosis H37Rv were evaluated.
      The results showed that both antigens, Mtb8.4-HspX and HspX-Mtb8.4, could elicit
      strong human T cell responses. With the existing of DDA adjuvant, HspX-Mtb8.4
      induced significantly higher secretion level of IFN-gamma and TNF-alpha in spleen
      cells than Mtb8.4-HspX (p<0.05). In its protective efficacy study, the isolated
      bacterial Colony Form Unit (CFU) in H8.4-DPG group was significantly reduced
      compared to 8.4H-DPG group (p<0.05). Furthermore, with the stimulation of Mtb8.4
      in vitro, the secretion of IFN-gamma and TNF-alpha from mice immunized with 20MUg
      of H8.4 exhibited relative higher level than the group immunized by 7MUg of H8.4
      (p<0.05), whereas, IL-2 secreting showed contrary result. The data suggest that
      the antigen sequential order and dose selection should be considered when a
      tuberculosis protein vaccine is to be constructed and its immune strategy is to
      be planned.

PMID- 29045912
TI  - The lived experience of first year undergraduate student nurses: A hermeneutic
      phenomenological study.
AB  - INTRODUCTION: This study gives insight into the experiences and perceptions of
      one group of undergraduate nursing students as they make the transition into
      Higher Education and the nursing profession, during the first year, of their
      three-year programme. Research has shown that first year undergraduate experience
      is complex and challenging for any student. For undergraduate nursing students,
      the process of achieving additional professional practice competencies required
      for United Kingdom nursing registration adds additional responsibility and
      potentially, more pressure. Few studies have considered student nurses' lived
      experiences during their first year of study in any depth. STUDY AIM: This study
      aimed to understand how one group of undergraduate nursing students perceived
      their experiences of the transition into higher education and nursing profession.
      DESIGN: Framed within an interpretive philosophical paradigm, a hermeneutic
      phenomenological approach enabled the exploration of participants' lived
      experiences. SETTING AND PARTICIPANTS: The study took place at a Higher Education
      Institution approved nurse education provider in the North of England, United
      Kingdom (UK). Following ethical approval, ten first year student nurses from a
      range of different backgrounds gave informed consent to participate. METHODS:
      Over a one year period between 2013 and 2014 participants provided data at three
      points during their first year (four months, eight months and twelve months) via
      semi-structured, digitally recorded individual interviews (n=30) and digital
      recordings of critical incident accounts as they occurred (n=30). Data was
      transcribed verbatim, systematically thematically analysed drawing on hermeneutic
      phenomenological principles and verified for thematic accuracy by participants in
      2015. FINDINGS: Five themes emerged from the data: uncertainty; expectations;
      learning to survive; seeking support; and moving forward. Findings identify that
      the participants had developed skills to survive however considerable variation
      in their experience, influenced motivation and behaviour. They developed their
      own skills of coping to deal with the demands of academic life and those of the
      practice setting. An explanatory student journey model demonstrated that
      developing self-efficacy was key to their successful transition through the first
      year of undergraduate study. CONCLUSIONS: Understanding the first year student
      nurse perspective and insight into their coping strategies are key to supporting
      a positive learning journey. Positive feedback from nurse educators, a growing
      sense of nursing community and motivation to succeed facilitates their
      internalisation of nursing identity, norms and values and an active pursuit of
      learning towards graduate status and becoming a nurse.

PMID- 29045913
TI  - Team based learning in nursing and midwifery higher education; a systematic
      review of the evidence for change.
AB  - REVIEW AIM: The aim of this study is to review the evidence in relation to the
      experiences and outcomes of students on nursing and/or midwifery higher education
      programmes, who experience team based learning. REVIEW OBJECTIVES: To examine the
      relationship between team based learning and attainment for nursing and midwifery
      students in professional higher education. To examine the relationship between
      team based learning and student satisfaction for nurses and midwifery students in
      higher education. To identify and report examples of good practice in the
      implementation of team based learning in Nursing and Midwifery higher education.
      DESIGN: A systematic Review of the literature was undertaken. The population were
      nurses and midwives studying on higher education pre and post registration
      professional programmes. The intervention was learning and teaching activities
      based on a team-based learning approach. Data sources included CINAHL and
      MEDLINE. ERIC and Index to Theses were also searched. REVIEW METHODS:
      International research papers published in English between 2011 and 2017 that met
      the inclusion criteria were included in the study. Papers that met the criteria
      were subjected to quality appraisal and agreement amongst authors for inclusion
      in the review. RESULTS: A total of sixteen papers were reviewed and four themes
      emerged for discussion. These were Student Engagement, Student Satisfaction,
      Attainment and Practice Development and Transformational Teaching and Learning.
      CONCLUSIONS: There is a tentative, though growing body of evidence to support TBL
      as a strategy that can impact on student engagement, student satisfaction,
      attainment, practice development and transformative teaching and learning. The
      literature indicates that implementing TBL within the curriculum is not without
      challenge and requires a sustained and structured approach. Staff and students
      need to understand the processes involved, and why they should be adhered to, in
      the pursuit of enhanced student experiences and outcomes for nurses and midwives
      in Higher Education.

PMID- 29045914
TI  - Suicide exposures and bereavement among American adults: Evidence from the 2016
      General Social Survey.
AB  - BACKGROUND: We investigated lifetime suicide exposures and bereavement among a
      representative sample of American adults from the 2016 General Social Survey.
      METHODS: Questions on lifetime suicide exposures, bereavement and mental health
      status were administered to 1432 respondents. Suicide exposed and bereaved
      respondents were compared to non-exposed respondents on three different measures
      of mental health functioning with cross tabulations and means comparison tests.
      RESULTS: 51% of respondents had exposures to one suicide or more during their
      lifetimes, and 35% were deemed bereaved by suicide, having experienced moderate
      to severe emotional distress from their losses. Findings suggested more exposures
      and bereavements were associated with greater numbers of bad mental health days
      and more expectations of "having nervous breakdowns" but with no clear
      associations with CES-D scores. CONCLUSIONS: These findings suggest suicide
      exposures and bereavement are far more pervasive than commonly thought, with more
      than half of the population exposed and a third bereaved. Health professionals
      need to more actively assess for suicide exposures and bereavements, and be
      vigilant for significant impacts of suicide even when the suicide decedent is not
      a first degree family relative, helping to reduce the mental health distress
      presently associated with these experiences.

PMID- 29045915
TI  - Acute psychoactive effects of intravenous ketamine during treatment of mood
      disorders: Analysis of the Clinician Administered Dissociative State Scale.
AB  - INTRODUCTION: Ketamine has rapid-acting antidepressant effects. Frequently,
      ketamine administration also causes acute psychoactive effects - in trials, these
      effects are commonly measured using the Clinician Administered Dissociative State
      Scale (CADSS). However, the CADSS was not designed for this specific purpose,
      having been validated in other clinical contexts, and anecdotally does not appear
      to fully capture ketamine's acute psychoactive effects. METHODS: Data were
      obtained from 110 individuals with mood disorders (predominantly major depressive
      disorder) who underwent intravenous ketamine infusion. An exploratory factor
      analysis (EFA) was performed on the CADSS, along with assessment of internal
      consistency. Qualitative methods were used to conduct in-depth interviews with a
      subset of these participants to identify key features of the acute ketamine
      experience, including aspects that may not be captured by the CADSS. RESULTS: The
      mean total score of the CADSS was low at 7.7 (SD 9.2). Analysis of internal
      consistency showed a Cronbach's alpha of 0.74. Five CADSS items had low
      correlations with the total score. EFA lead to a one-factor solution containing
      16 items. Five of the six highest loading items involved perceptual disturbances,
      either of time or sensation. Qualitative analyses of 10 patient narratives
      revealed two phenomena not captured on the CADSS: disinhibition and a sense of
      peace. LIMITATIONS: This study was by limited by the absence of other ratings of
      the participants' experience. CONCLUSION: Findings suggest that the CADSS
      partially captures the acute effects of ketamine administration. Further research
      may seek to validate a revised version of the CADSS that more accurately measures
      these effects.

PMID- 29045916
TI  - Suicide deaths among patients with end-stage renal disease receiving dialysis: A
      population-based retrospective cohort study of 64,000 patients in Taiwan.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) who receive dialysis may
      experience increased distress and risk of suicide. METHODS: This population-based
      retrospective cohort study linked Taiwan's national register of ESRD patients on
      dialysis and the cause-of-death mortality data file. A separate multiple-cause-of
      death data file was used to investigate the detailed suicide methods used.
      Standardized mortality ratios (SMRs) were calculated for the overall patient
      group and by sex, age, year of initiating dialysis, method of suicide, and time
      since initiation of dialysis. RESULTS: Among 63,854 ESRD patients on dialysis,
      133 died by suicide in Taiwan in 2006-2012; the suicide rate was 76.3 per 100,000
      patient-years. The SMR for suicide was 2.38 (95% confidence interval [CI] 1.99
      2.82) in this patient group. Suicide risk was highest in the first year of
      dialysis (SMR = 3.15, 95% CI 2.39-4.08). The risk of suicide by cutting was
      nearly 20 times (SMR = 19.91, 95% CI 12.88-29.39) that of the general population.
      Detailed information on death certificates indicated that three quarters of
      patients who killed themselves by cutting cut vascular accesses used for
      hemodialysis. LIMITATIONS: Information on risk factors such as socioeconomic
      position and mental disorders was unavailable. CONCLUSION: In a country where the
      national health insurance program covers most expenses associated with dialysis
      treatment, the suicide risk in ESRD patients on dialysis still increased nearly
      140%. Adequate support for ESRD patients initiating dialysis and the assessment
      of risk of cutting vascular access as a potential means of suicide could be
      important strategies for suicide prevention.

PMID- 29045917
TI  - Learning to infer the time of our actions and decisions from their consequences.
AB  - Research shows that people infer the time of their actions and decisions from
      their consequences. We asked how people know how much time to subtract from
      consequences in order to infer their actions and decisions. They could either
      subtract a fixed, default, time from consequences, or learn from experience how
      much time to subtract in each situation. In two experiments, participants'
      actions were followed by a tone, which was presented either immediately or after
      a delay. In Experiment 1, participants estimated the time of their actions; in
      Experiment 2, the time of their decisions to act. Both actions and decisions were
      judged to occur sooner or later as a function of whether consequences were
      immediate or delayed. Estimations tended to be shifted toward their consequences,
      but in some cases they were shifted away from them. Most importantly, in all
      cases participants learned progressively to adjust their estimations with
      experience.

PMID- 29045918
TI  - Cervical cancer cells (HeLa) response to photodynamic therapy using a zinc
      phthalocyanine photosensitizer.
AB  - Cervical cancer is the most common gynecological malignancy worldwide, and the
      leading cause of cancer related deaths among females. Conventional treatment for
      early cervical cancer is radical hysterectomy. In locally advanced cancer the
      treatment of choice is concurrent chemo radiation. Although such treatment
      methods show promise, they do have adverse side effects. To minimize these
      effects, as well as prevent cancer re-occurrence, new treatment methods are being
      investigated. Photodynamic therapy (PDT) involves the selective uptake of a
      photosensitizer (PS) by cancer cells, illumination with light of an appropriate
      wavelength that triggers a photochemical reaction leading to the generation of
      reactive oxygen and subsequent tumor regression. The effect of PDT on a cervical
      cancer cell line (HeLa) was assessed by exposing cultured cells to a sulphonated
      zinc phthalocyanine PS (ZnPcSmix) and irradiating the cells using a 673nm diode
      laser. The effects were measured using the Trypan blue viability assay, adenosine
      triphosphate assay (ATP) luminescence assay for proliferation, Lactate
      Dehydrogenase (LDH) membrane integrity cytotoxicity assay, and fluorescent
      microscopy to assess PS cellular localization and nuclear damage. Fluorescent
      microscopy revealed localization of the PS in the cytoplasm and perinuclear
      region of HeLa cells. PDT treated cellular responses showed dose dependent
      structural changes, with decreased cell viability and proliferation, as well as
      considerable membrane damage. Hoechst stained cells also revealed DNA damage in
      PDT treated cells. The final findings from this study suggest that ZnPcSmix is a
      promising PS for the PDT treatment of cervical cancer in vitro, where a
      significant 85% cellular cytotoxicity with only 25% cellular viability was noted
      in cells which received 1MUM ZnPcSmix when an 8J/cm2 fluence was applied.

PMID- 29045919
TI  - Altered attentional control strategies but spared executive functioning in
      chronic cannabis users.
AB  - BACKGROUND: Cannabis use has increased rapidly in recent decades. The increase in
      cannabis use makes it important to understand the potential influence of chronic
      use on attentional control and other executive functions (EFs). Because cannabis
      is often used to reduce stress, and because stress can constrain attentional
      control and EFs, the primary goal of this study was to determine the joint effect
      of acute stress and chronic cannabis use on specific EFs. METHODS: Thirty-nine
      cannabis users and 40 non-users were assigned to either a stress or no stress
      version of the Maastricht Acute Stress Test. Participants then completed two
      cognitive tasks that involve EFs: (1) task switching, and (2) a novel Flexible
      Attentional Control Task. These two tasks provided assessments of vigilant
      attention, inhibitory control, top-down attentional control, and cognitive
      flexibility. Salivary cortisol was assessed throughout the study. RESULTS:
      Reaction time indices showed an interaction between stress and cannabis use on
      top-down attentional control (p=0.036, np2=0.059). Follow-up tests showed that
      cannabis users relied less on top-down attentional control than did non-users in
      the no stress version. Despite not relying on top-down control, the cannabis
      users showed no overall performance deficits on the tasks. CONCLUSIONS: Chronic
      cannabis users performed cognitive tasks involving EFs as well as non-users while
      not employing cognitive control processes that are typical for such tasks. These
      results indicate alterations in cognitive processing in cannabis users, but such
      alterations do not necessarily lead to global performance deficits.

PMID- 29045921
TI  - Commonalities and differences in the neural representations of English,
      Portuguese, and Mandarin sentences: When knowledge of the brain-language mappings
      for two languages is better than one.
AB  - This study extended cross-language semantic decoding (based on a concept's fMRI
      signature) to the decoding of sentences across three different languages
      (English, Portuguese and Mandarin). A classifier was trained on either the
      mapping between words and activation patterns in one language or the mappings in
      two languages (using an equivalent amount of training data), and then tested on
      its ability to decode the semantic content of a third language. The model trained
      on two languages was reliably more accurate than a classifier trained on one
      language for all three pairs of languages. This two-language advantage was
      selective to abstract concept domains such as social interactions and mental
      activity. Representational Similarity Analyses (RSA) of the inter-sentence neural
      similarities resulted in similar clustering of sentences in all the three
      languages, indicating a shared neural concept space among languages. These
      findings identify semantic domains that are common across these three languages
      versus those that are more language or culture-specific.

PMID- 29045920
TI  - The association of alcohol consumption patterns with self-rated physical health
      and psychiatric distress among Afghanistan- and Iraq-era U.S. veterans.
AB  - Alcohol misuse is associated with negative mental and physical health outcomes,
      which presents a public health concern in veterans. However, less is known
      regarding outcomes among veterans with low to moderate alcohol consumption. This
      study included veterans with military service in Iraq and/or Afghanistan (N =
      1083) who resided in the VA Mid-Atlantic region catchment area (North Carolina,
      Virginia, and parts of West Virginia). Participants completed a mailed survey
      that inquired about demographics, past-year alcohol consumption, self-rated
      physical health, and psychiatric symptoms. Logistic regression was used to
      evaluate associations between alcohol consumption and posttraumatic stress
      disorder (PTSD), depression, and self-rated physical health. In both bivariate
      results and adjusted models, non-drinkers and hazardous drinkers were more likely
      to endorse clinically significant PTSD and depression symptoms than moderate
      drinkers. Moderate drinkers were also less likely to report fair/poor health,
      after adjusting for demographics and psychiatric symptoms. Results overall showed
      a U-shaped curve, such that moderate alcohol use was associated with lower rates
      of mental health problems and fair/poor health. While the VA routinely screens
      for alcohol misuse, current results suggest that non-drinkers are also at risk
      for poor mental and physical health.

PMID- 29045922
TI  - The impact of expired commercial drugs on non-target marine species: A case study
      with the use of a battery of biomarkers in hemocytes of mussels.
AB  - The present study investigated the effects of two expired commercial medicines,
      like Buscopan Plus and Mesulid, commonly classified as household medical wastes,
      on hemocytes of mussel Mytilus galloprovincialis. Mussel hemocytes' lysosomal
      membrane stability (in terms of neutral red retention assay), superoxide anions
      (O2.-) and nitric oxides (NO, in terms of nitrites) production, lipid
      peroxidation (in terms of malondialdehyde/MDA content) and the formation of
      nuclear abnormalities (using the micronucleus/MN assay) were assessed in
      hemocytes of mussels treated for 7 days with appropriate amounts of each drug
      (the concentrations of active substances were considered in each case, due to the
      absence of data related with the excipients) as well as in hemocytes of post
      treated/recovered mussels (7 days post-treatment/recovery period). According to
      the results, treated mussels showed significantly decreased NRRT values, enhanced
      O2.-, NO and MDA levels, as well as high frequencies of nuclear abnormalities in
      both cases. Thomicronse effects showed a drastic reduction in almost all cases,
      after the post-treatment/recovery period. Moreover, the "stress on stress"
      method, commonly performed for estimating mussels' ability to survive in air,
      showed significantly reduced LT50 values in challenged mussels, compared to
      values observed in control mussels. The current findings revealed for the first
      time that both expired commercial drugs could affect mussels, probably via the
      formation of active substances bioactivated metabolites, as well as excipients,
      such as TiO2 and SiO2, at least in case of Buscopan plus. Although further
      research is needed, the current findings indicate the environmental impact of
      expired commercial drugs, thus revealing the need for the proper disposal of
      household medical wastes.

PMID- 29045923
TI  - Harvesting and contamination control of microalgae Chlorella ellipsoidea using
      the bio-polymeric flocculant alpha-poly-l-lysine.
AB  - Microalgae have been extensively studied for the production of various products.
      However, to date, microalgal biomass has not become economically feasible, mainly
      due to different issues such as contamination from various sources that occurs
      during downstream processes, and which leads to low quality biomass with limited
      application. In this study, to overcome contamination by flocculants and other
      microorganisms, the cationic biopolymer alpha-Poly-l-lysine (alpha-PLL) was
      applied. The cationic amine moiety and polymeric chain of alpha-PLL rendered
      microalgal harvesting efficient. With increasing alpha-PLL chain length,
      efficient dose- and time-dependent harvesting was achieved. In addition to
      efficient flocculation performance, biomass harvested using alpha-PLL showed
      suppressed biological contamination through the inherent antimicrobial activity
      of alpha-PLL. Thus, it is possible to upgrade the quality and storability of
      produced microalgal biomass using alpha-PLL-induced flocculation.

PMID- 29045924
TI  - Alternatively permutated conic baffles generate vortex flow field to improve
      microalgal productivity in a raceway pond.
AB  - Alternatively permutated conic (APC) baffles were proposed to generate vertical
      and horizontal vortex flow to intensify mixing and mass transfer in a raceway
      pond. Both clockwise vortexes were generated before and after conic baffles in
      the main stream to increase perpendicular velocity by 40.3% and vorticity
      magnitude by 1.7 times on vertical cross section. Self-rotary flow around conic
      baffles and vortex flow among conic baffles were generated to increase
      perpendicular velocity by 80.4% and vorticity magnitude by 4.2 times on
      horizontal cross section. The bubble generation time and diameter decreased by
      25.5% and 38.7%, respectively, while bubble residence time increased by 84.3%.
      The solution mixing time decreased by 48.1% and mass transfer coefficient
      increased by 34.0% with optimized relative spacing (epsilon) and height (omega)
      of conic baffles. The biomass productivity of Spirulina increased by 39.6% under
      pure CO2 with APC baffles in a raceway pond.

PMID- 29045925
TI  - Mixotrophic Chlorella sp. UJ-3 cultivation in the typical anaerobic fermentation
      effluents.
AB  - The growth of mixotrophic Chlorella sp. UJ-3 cultivated in the three typical
      anaerobic fermentation effluents was investigated in this paper. The results
      showed that the microalgae grew best under intermediate light intensity for all
      the types of fermentation effluents. The butyrate type fermentation effluents
      induced the fastest growth rate for Chlorella sp. UJ-3, with a maximal cell
      concentration of 3.8*107 cells/mL. Under intermediate light intensity, the
      volatile fatty acids (VFAs) were almost depleted on the fifth day of the
      cultivation for all the three types of fermentation systems. The ratios of
      chlorophyll a/b were all increased for the three systems, indicating enhanced
      energy-capturing capability of the microalgae for photosynthesis after the VFAs
      were depleted. The highest lipid content was 25.4%dwt achieved in the butyrate
      type fermentation, and the fatty acid compositions were found to be considerably
      different for these three types of fermentation systems.

PMID- 29045926
TI  - Enhanced enzymatic saccharification of sugarcane bagasse pretreated by sodium
      methoxide with glycerol.
AB  - Sodium methoxide (CH3ONa) with glycerol pretreatment (CWGP) was performed to
      improve the enzymatic digestibility of sugarcane bagasse (SCB). Response surface
      methodology was utilized to optimize the CWGP parameters for pretreating SCB from
      the perspective of total fermentable sugar yield (TFSY) and total fermentable
      sugar concentration (TFSC). Under the optimal CWGP conditions, 0.5666g/g of TFSY
      (0.82% CH3ONa, 1.11h, 150 degrees C) and 17.75g/L of TFSC (0.87% CH3ONa, 1.38h,
      149.27 degrees C) were achieved, corresponding to delignification of 79.05% and
      79.34%, respectively. Compared the pretreatment using glycerol or CH3ONa alone,
      the CWGP has significant synergies to enhance the enzymatic efficiency of SCB.
      The physical and chemical characteristics of untreated and pretreated SCBs were
      analyzed using FT-IR, XRD, and SEM, and the results suggest that CWGP
      significantly increased the susceptibility of the substrates to enzymatic
      digestibility. Ultimately, CWGP might be a prospective candidate for the
      pretreatment process of enzyme-based lignocellulosic biorefineries.

PMID- 29045927
TI  - Alkaline pH shock enhanced production of validamycin A in fermentation of
      Streptomyces hygroscopicus.
AB  - Validamycin A (Val-A) is produced by Streptomyces as a secondary metabolite with
      wide agricultural applications of controlling rice sheath blight, false smut and
      damping-off diseases. The effect of alkaline pH shock on enhancing Val-A
      production and its mechanism were investigated. A higher yield of Val-A was
      achieved by NaOH shock once or several times together with faster protein
      synthesis and sugar consumption and alkaline pH shock can increase Val-A
      production by 27.43%. Transcription of genes related to amino acid metabolism,
      carbon metabolism and electron respiratory chain was significantly up-regulated,
      accompanied by the substantial increase of respiratory activity and glutamate
      concentration. Val-A production was promoted by a series of complex mechanisms
      and made a response to pH stress signal, which led to the enhancement of
      glutamate metabolism and respiration activity. The obtained information will
      facilitate future studies for antibiotic yield improvement and the deep
      revealment of molecular mechanism.

PMID- 29045928
TI  - Factors associated with alcohol consumption among medical cannabis patients with
      chronic pain.
AB  - INTRODUCTION: Chronic pain is the most common reason for medical cannabis
      certification. Data regarding alcohol use and risky drinking among medical
      cannabis patients with pain is largely unknown. Therefore, we examined the
      prevalence and correlates of alcohol use and risky drinking in this population.
      METHODS: Participants completed surveys regarding demographics, pain-related
      variables, anxiety, cannabis use, and past six-month alcohol consumption. Alcohol
      use groups were defined using the AUDIT-C [i.e., non-drinkers, low-risk drinkers,
      and high-risk drinkers (>=4 for men and >=3 for women)] and compared on
      demographic characteristics, pain measures, anxiety, and cannabis use. RESULTS:
      Overall, 42% (n=330/780) were non-drinkers, 32% (n=251/780) were low-risk
      drinkers, and 26% (n=199/780) were high-risk drinkers. Compared to non-drinkers,
      low- and high-risk drinkers were significantly younger whereas a larger
      proportion of low-risk drinkers reported being African-American compared to non-
      or high-risk drinkers. High-risk drinkers reported significantly lower pain
      severity/interference compared to the other groups; high-risk drinkers were also
      less likely to be on disability compared to other groups. A multinomial logistic
      regression showed that patients reporting lower pain severity and less disability
      had greater odds of being classified a high-risk drinker. CONCLUSIONS: High-risk
      drinking appears common among medical cannabis patients. Future research should
      examine whether such use is concurrent or consecutive, and the relationship of
      such co-use patterns to consequences. Nevertheless, individuals treating patients
      reporting medical cannabis use for pain should consider alcohol consumption, with
      data needed regarding the efficacy of brief alcohol interventions among medical
      cannabis patients.

PMID- 29045929
TI  - Deciphering the complexation process of a fluoroquinolone antibiotic,
      levofloxacin, with bovine serum albumin in the presence of additives.
AB  - The current work aims to explore the thermodynamic and conformational aspects for
      the binding of fluoroquinolone antibacterial drug, levofloxacin (LFC), with
      bovine serum albumin (BSA) using calorimetric, spectroscopic (UV-visible,
      fluorescence, circular dichroism, and 1H NMR), dynamic light scattering (DLS) and
      computational methods (molecular docking). The binding of LFC with BSA at two
      sequential sites with higher affinity (~103M-1) at the first site has been
      explored by calorimetry whereas the binding at a single site with affinity of the
      order of ~104M-1 has been observed from fluorescence spectroscopy. The
      calorimetric study in the presence of additives along with docking analysis
      reveals the significant role of electrostatic, hydrogen bonding, and hydrophobic
      interactions in the association process. The slight conformational changes in
      protein as well as the changes in the water network structure around the binding
      cavity of protein have been observed from spectroscopic and DLS measurements. The
      LFC induced quenching of BSA fluorescence was observed to be initiated mainly
      through the static quenching process and this suggests the formation of ground
      state LFC-BSA association complex. The stronger interactions of LFC in the cavity
      of Sudlow site I (subdomain IIA) of protein have been explored from site marker
      calorimetric and molecular docking study.

PMID- 29045930
TI  - Label-free aptamer-based sensor for specific detection of malathion residues by
      surface-enhanced Raman scattering.
AB  - A novel label-free aptamer surface-enhanced Raman scattering (SERS) sensor for
      trace malathion residue detection was proposed. In this process, the binding of
      malathion molecule with aptamer is identified directly. The silver nanoparticles
      modified with positively charged spermine served as enhancing and capture
      reagents for the negatively charged aptamer. Then, the silver nanoparticles
      modified by aptamer were used to specifically capture the malathion. The SERS
      background spectra of spermine, aptamer, and malathion were recorded and
      distinguished with the spectrum of malathion-aptamer. To enhance the
      characteristic peak signal of malathion captured by the aptamer, the aggregate
      reagents (NaCl, KCl, MgCl2) were compared and selected. The selectivity of this
      method was verified in the mixed-pesticide standard solution, which included
      malathion, phosmet, chlorpyrifos-methyl, and fethion. Results show that malathion
      can be specifically identified when the mixed-pesticide interferences existed.
      The standard curve was established, presenting a good linear range of 5*10-7 to
      1*10-5mol.L-1. The spiked experiments for tap water show good recoveries from
      87.4% to 110.5% with a relative standard deviation of less than 4.22%. Therefore,
      the proposed label-free aptamer SERS sensor is convenient, specifically detects
      trace malathion residues, and can be applied for qualitative and quantitative
      analysis of other pesticides.

PMID- 29045931
TI  - Capacitive deionization of a RO brackish water by AC/graphene composite
      electrodes.
AB  - A feasibility study for water recycling and reuse of a reverse osmosis (RO)
      brackish wastewater by capacitive deionization (CDI) was carried out in the
      present work. Palm-shell wastes enriched in carbon was recycled to yield valuable
      activated carbon (AC) that has advantages of high surface area, high specific
      capacitance, and low electrical resistance as the CDI electrodes. The GAC
      prepared by dispersion of AC in the graphene (rGO) layers has a high surface area
      and electrical conductivity for CDI. The GAC electrodes have increasing
      electrosorption efficiencies from 1.6 to 3.0% during the repeated electrosorption
      regeneration cycles under +1.2 -> 0 -> +1.2 V while the efficiencies the AC
      electrodes decrease from 2.7 to 1.6%. It is clear that the GAC-based electrodes
      have a better electrosorption efficiency and stability in, for example, the three
      repeated electrosoption-regeneration cycles for CDI of the wastewater. This work
      also exemplifies that the AC recycled from biomass such as palm-shell wastes can
      be used in CDI electrodes for recycling and reuse of wastewater.

PMID- 29045933
TI  - Chemical transformation of silver nanoparticles in aquatic environments:
      Mechanism, morphology and toxicity.
AB  - Silver nanoparticles (Ag NPs) have been inevitably introduced into ecological
      environment during their extensive applications in daily human life.
      Thermodynamically, Ag NPs are unstable and transform into other species under
      various aqueous conditions. Ag NPs and their transformation products pose
      potential threats to environment and humans. However, the complex environmental
      conditions and transformations of Ag NPs complicate their human health and
      environmental risk assessment. To bridge the knowledge gap, four essential
      environmental transformations, oxidative dissolution, sulfidation, chlorination
      and photoreduction, of Ag NPs are reviewed herein. The mechanism, morphology and
      size change, as well as the toxicity of Ag NPs during these transformations under
      certain aqueous conditions are detailed. In particular, these environmental
      transformations have shown strong correlations that are discussed. The
      transformation, fate, bioavailability, morphology and toxicity of Ag NPs are
      critical factors and should be considered in a complete human health and
      environmental risk assessment of Ag NPs. The fluctuation of these factors in the
      realistic environment is also vital and should be considered.

PMID- 29045932
TI  - Modulation of sestrin confers protection to Cr(VI) induced neuronal cell death in
      Drosophila melanogaster.
AB  - Increased oxidative stress is one of the major causes of hexavalent chromium
      [Cr(VI)], a heavy metal with diverse applications and environmental presence,
      induced neuronal adversities in exposed organism including Drosophila. Sestrin
      (sesn), an oxidative stress responsive gene, emerges as a novel player in the
      management of oxidative stress response. It is reported to be regulated by Target
      of rapamycin (TOR) and the former regulates autophagy and plays an important role
      in the prevention of neurodegeneration. Due to limited information regarding the
      role of sesn in chemical induced cellular adversities, it was hypothesized that
      modulation of sesn may improve the Cr(VI) induced neuronal adversities in
      Drosophila. Upon exposure of Cr(VI) (5.0-20.0 MUg/ml) to D. melanogaster larvae
      (w1118; background control), neuronal cell death was observed at 20.0 MUg/ml of
      Cr(VI) concentration which was found to be reversed by targeted sesn
      overexpression (Elav-GAL4>UAS-sesn) in those cells of exposed organism by the
      induction of autophagy concomitant with decreased reactive oxygen species (ROS)
      level, p-Foxo-, p-JNK- and p-Akt-levels with decreased apoptosis. Conversely,
      after sesn knockdown (Elav-GAL4>UAS-sesnRNAi) in neuronal cells, they become more
      vulnerable to oxidative stress and apoptosis. Furthermore, knockdown of sesn in
      neuronal cells of exposed organism resulted in decreased autophagy with increased
      TOR and p-S6k levels while overexpression of sesn led to their decreased levels
      suggestive of decreased anabolic and increased catabolic activity in neuronal
      cells shifting energy towards the augmentation of cellular repair. Taken
      together, the study suggests therapeutic implications of sesn against chemical
      induced neuronal adversities in an organism.

PMID- 29045934
TI  - A comparison of genotoxicity change in reclaimed wastewater from different
      disinfection processes.
AB  - Effluents before disinfection from four wastewater reclamation plants were
      treated with chlorine (Cl2), ozone (O3), chlorine dioxide (ClO2), medium-pressure
      ultraviolet (MPUV) and four different combinations of the above, to evaluate the
      effect of disinfection processes on the genotoxicity removal by the SOS/umu test.
      Results showed that the genotoxicity increased after MPUV irradiation (10-100
      mJ/cm2), but declined when adopting other disinfection processes. The
      effectiveness of genotoxicity reduction by five chemical disinfectants was
      identified as: O3 > pre-ozonation with Cl2 ~ ClO2 > combination of ClO2 and Cl2 >
      Cl2. The sequential combination of MPUV, Cl2 and O3 reduced the genotoxicity to a
      level similar to the source water. The influence of differential disinfection
      process varied on iodinated wastewater, which is closely related to the
      competitive reactions between disinfectants, iodine and dissolved organic
      matters. The removal of genotoxic pollutants and the formation of genotoxic
      disinfection by-products are the two major factors that lead to the change in
      genotoxicity during disinfection.

PMID- 29045935
TI  - Emodinol ameliorates urate nephropathy by regulating renal organic ion
      transporters and inhibiting immune inflammatory responses in rats.
AB  - Emodinol, 1beta, 3beta, 23-trihydroxyolean-12-en-28-acid, as the main active
      ingredient firstly extracted from the rhizomes of Elaeagus pungens by our
      Research Group, was identified with apparent uricosuric and nephroprotective
      effects in hyperuricemia mice in our previous study. This study aimed to
      investigate the renal protective effect of emodinol in urate nephropathy rats.
      Rats were orally administrated by combined adenine and ethambutol to induce urate
      nephropathy. Emodinol at various doses were administered intragastrically to
      urate nephropathy rats daily. Serum uric acid (Sur), serum creatinine (Scr) and
      blood urea nitrogen (BUN) levels, as well as Interleukin-1beta (IL-1beta) and
      tumor necrosis factor- alpha (TNF-alpha) concentrations in serum and kidney were
      determined. Renal protein expressions of organic ion transporters, components of
      NLR pyrin domain containing 3 (NLRP3) inflammasome, as well as key factors
      involved in toll-like receptors (TLRs)/myeloid differentiation factor 88
      (MyD88)/nuclear factor kappa B (NF-kappaB) signaling pathway were analyzed by
      western blot. Emodinol significantly decreased Sur, Scr and BUN levels in adenine
      and ethambutol - induced urate nephropathy rats. More importantly, emodinol
      reversed dys-expression of organic ion transporters, inhibited NLRP3 inflammsome
      activation and suppressed TLRs/MyD88/NF-kappaB signaling pathway in the kidneys
      of urate nephropathy rats. Consistently, dilated tubules and tubular UA crystal
      formation, as well as tubular interstitial inflammatory cells infiltration in
      kidneys of urate nephropathy rats were obviously attenuated by emodinol,
      accompanied by restored renal and serum inflammatory cytokines concentrations.
      Taken together, the date suggested that emodinol ameliorated urate nephropathy by
      regulating renal organic ion transporters and inhibiting immune inflammatory
      responses in rats.

PMID- 29045936
TI  - Anti-Diabetic Potential of the Leaves of Anisomeles malabarica in Streptozotocin
      Induced Diabetic Rats.
AB  - BACKGROUND/AIMS: Diabetes mellitus is a pandemic metabolic disorder that is
      affecting a majority of populations in recent years. There is a requirement for
      new drugs that are safer and cheaper due to the side effects associated with the
      available medications. METHODS: We investigated the anti-diabetic activity of
      leaves of Anisomeles malabarica following bioactivity guided fractionation. The
      different solvent (hexane, ethyl acetate, methanol and water) extracts of A.
      malabarica leaves were used in acute treatment studies to evaluate and identify
      the active fraction. The ethyl acetate extract was subjected to further
      fractionation using silica gel column chromatography and the compounds were
      identified by LC-SRM/MS and GC-MS. Additional chronic treatment studies were
      carried out using this active fraction (AMAF) for 30 days in experimental
      diabetic rats. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c),
      plasma insulin levels and glucose tolerance were measured along with insulin
      resistance/sensitivity indicators (HOMA-IR, HOMA-beta and QUICKI) to assess the
      beneficial effects of A. malabarica in the management of diabetes mellitus.
      RESULTS: Among the different solvent extracts tested, ethyl acetate extract
      showed maximum (66%) anti-hyperglycemic activity. The hexane and ethyl acetate
      (1: 1) fraction that has maximum anti-diabetic activity was identified as active
      fraction of A. malabarica (AMAF). The FBG, HbA1c, plasma insulin levels and
      insulin sensitivity/resistance indicators such as glucose tolerance, HOMA-IR,
      HOMA-beta and QUICKI were significantly improved to near normal in diabetic rats
      treated with AMAF. Further, we identified key flavonoids and fatty acids as the
      anti-diabetic active principles from the AMAF of A. malabarica leaves.
      CONCLUSION: The results of our study suggest that Anisomeles malabarica has
      potential anti-diabetic activity in STZ induced diabetic rats.

PMID- 29045937
TI  - Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem
      Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head
      Osteonecrosis in Beagle Dogs.
AB  - BACKGROUND: This study investigated the effect of using adenovirus-mediated
      expression of bone morphogenetic protein 2 (Ad-BMP-2) and basic fibroblast growth
      factor (bFGF) in bone marrow mesenchymal stem cells (BMSCs) in combination with a
      demineralized bone matrix (DBM) to repair osteonecrosis of the femoral head
      (ONFH) in Beagle dogs. METHODS: A total of 30 Beagle dogs were selected for the
      isolation of BMSCs, which were cultured and transfected with the recombinant
      adenovirus vector Ad-BMP2-bFGF-GFP (carrying BMP-2 and bFGF) or a control
      adenovirus plasmid (encoding green fluorescent protein (Ad-GFP)). The expression
      of the transfected BMP-2 and bFGF proteins was detected by Western blotting.
      After transfection, the BMSCs were induced to undergo osteoblastic
      differentiation. The DBM was prepared to construct a DBM/BMSC complex. Beagle
      models of canine femoral head defects and necrosis were established and divided
      into control, DBM, DBM/BMSC, vector Ad-BMP2-bFGF-GFP and Ad-GFP groups. The
      composite graft was then implanted, and new bone morphology was visualized via X
      ray at 3, 6 and 12 weeks after the operation. Hematoxylin and eosin (HE) staining
      and Masson's trichrome staining were used to identify new bone formation.
      Immunohistochemistry was performed to calculate the density of new blood vessels.
      The compressive and bending strength of the BMSCs was evaluated at 12 weeks after
      the operation. RESULTS: BMSCs were successfully isolated. The protein expression
      of BMP-2 and bFGF was significantly higher in the Ad-BMP-2/bFGF group than the
      normal and Ad-GFP groups. Compared with the control group, at 12 weeks after the
      operation, the DBM, DBM/BMSC, vector Ad-BMP2-bFGF-GFP and Ad-GFP groups showed a
      larger area of new bone, higher X-ray scores, greater neovascularization density,
      and increased compressive and bending strength. The most significant
      modifications occurred in thevector Ad-BMP2-bFGF-GFP group. CONCLUSION: The
      results indicate that the use of Ad-BMP-2/bFGF-modified BMSCs in conjunction with
      DBM could successfully repair ONFH in a dog model by promoting bone formation and
      angiogenesis.

PMID- 29045938
TI  - Effectiveness of Nivolumab versus Docetaxel as Second-Line Treatment in Non-Small
      Cell Lung Cancer Patients in Clinical Practice.
AB  - AIMS: To evaluate the effectiveness of nivolumab as second-line treatment
      compared to standard therapy with docetaxel in adult patients with non-small cell
      lung cancer (NSCLC) in clinical practice. METHODS: This is an observational,
      retrospective cohort study of adult patients diagnosed with NSCLC, stage III-IV,
      treated with docetaxel or nivolumab as second-line treatment. The end points
      evaluated were overall survival (OS) and progression-free survival (PFS). PFS and
      OS were described using the Kaplan-Meier method. The Cox proportional hazards
      model was applied to identify independent prognostic and predictive factors
      related to disease progression or death. RESULTS: Thirty-three patients were
      included in this study (i.e., 14 in the nivolumab group and 19 in the docetaxel
      group). Nonsquamous NSCLC was the most frequent histological subtype. Cohorts
      were homogeneous. The follow-up time was 116 +/- 87.3 days. The median PFS was 84
      days (95% CI 39-300) for patients treated with nivolumab and 61 days (95% CI 48
      76) for patients treated with docetaxel. The risk of progression was 60% lower
      for patients treated with nivolumab (HR 0.40; 95% CI 0.16-0.97; p = 0.043)
      compared to patients receiving docetaxel. Among the patients treated with
      docetaxel, the median OS was 129 days (95% CI 106-300). More than 50% of the
      patients treated with nivolumab were alive at the end of the follow-up period;
      nevertheless, the risk difference was not statistically significant (HR 0.55; 95%
      CI 0.20-1.51; p = 0.244). CONCLUSION: NSCLC patients treated with nivolumab as
      second-line therapy had a longer PFS compared to patients treated with docetaxel
      in a health care environment.

PMID- 29045939
TI  - Very-Low-Dose Decitabine Is Effective in Treating Intermediate- or High-Risk
      Myelodysplastic Syndrome.
AB  - Nowadays, the regular recommended dose of decitabine for the treatment of
      myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a
      relatively high incidence of treatment-related morbidities and costs. In this
      study, a retrospective and multicenter analysis was performed to explore the very
      low-dose decitabine schedule for the treatment of patients with IPSS intermediate
      or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in
      Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for
      7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months,
      10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and
      3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%.
      Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed
      among all courses. The median cost of each course was USD 5,300, 3,000, 2,900,
      and 2,000, respectively. Multivariate analysis identified bone marrow blast cells
      >=10% and a Charlson comorbidity index >=1 as 2 independent factors for efficacy.
      In conclusion, very-low-dose decitabine showed relatively good efficacy, good
      tolerance, and low medical cost in the treatment of intermediate- or high-risk
      MDS. Elderly patients with more than 1 complication or patients with a higher
      proportion of blast cells may be the most suitable candidates for this regimen.

PMID- 29045940
TI  - MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via
      Targeting Rab27a.
AB  - BACKGROUND/AIMS: With the aging population increases, senile osteoporosis has
      become a global public health problem. Previous evidence has shown that miR-124
      has important effects on the occurrence and development of osteoporosis. However,
      the role of miR-124 in the process of osteoclastogenesis is still obscure.
      METHODS: First of all, we measured the expression level of miR-124 in bone marrow
      monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we
      evaluated the alteration of miR-124 during osteoclast differentiation of BMMs.
      Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the
      influences of miR-124 on osteoclast differentiation of BMMs in vitro.
      Furthermore, bioinformatics analysis and luciferase reporter assay were performed
      for prediction and identification of the target of miR-124. RESULTS: BMMs from
      OVX mice exhibited lower expression of miR-124 compared with Sham mice.
      Additionally, miR-124 was down-regulated when BMMs differentiated into
      osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into
      osteoclasts in vitro, whereas overexpression of miR-124 attenuated this
      procedure, demonstrated by increased expression of osteoclast specific genes and
      TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR
      124 by bioinformatics, Western blot and luciferase reporter assay analysis.
      CONCLUSION: Our findings revealed that miR-124 has an important role in
      osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a
      therapeutic potential in the treatment of osteoporosis.

PMID- 29045941
TI  - Relationship Between Visit-to-Visit Blood Pressure Variability (BPV) and Kidney
      Function in Patients with Hypertension.
AB  - BACKGROUND/AIMS: To investigate the impact of kidney function (using estimated
      glomerular filtration rate, [eGFR]) on blood pressure variability (BPV) via a
      retrospective post hoc analysis of patients with hypertension enrolled in two
      large clinical trials. METHODS: Subject-level data were extracted from ASCOT
      (N=18,852) and ALLHAT (N=26,441) databases; both were randomized, active
      controlled studies, with treatment duration for hypertension >=4 years. Visit-to
      visit BPV was assessed using the square root of the coefficient of variation of
      systolic blood pressure (SBP) across visits from 12 weeks onwards. Baseline GFR,
      estimated by the simplified Modification of Diet in Renal Disease equation, was
      stratified into <=60, 61-90, and >90 mL/min/1.73 m2. The relationship between
      baseline eGFR and systolic BPV was analyzed using an analysis of covariance, with
      baseline factors considered as covariates. Studies were pooled and analyzed
      individually. RESULTS: Patient characteristics were largely consistent between
      studies. In the pooled population (n=38,133) there were 19.1%, 62.9%, and 18.0%
      patients, with eGFR <=60, 61-90, and > 90 mL/min/1.73 m2, respectively. Patients
      with lower baseline eGFR had higher systolic BPV, in the pooled population and
      the individual analyses. Other baseline predictors of high systolic BPV included
      high SBP and age, being male, and a smoker. An amlodipine-based regimen was a
      negative predictor of high systolic BPV, vs. other antihypertensives, regardless
      of eGFR. CONCLUSIONS: Patients with declining renal function tended to have
      higher systolic BPV vs. those without, even after adjusting for risk factors.
      Amlodipine-based therapy reduced BPV more than other antihypertensive agents,
      regardless of level of eGFR.

PMID- 29045943
TI  - Reference Ranges for Fetal Atrioventricular and Ventriculoatrial Time Intervals
      and Their Ratios during Normal Pregnancy.
AB  - BACKGROUND: The diagnostic assessment of fetal arrhythmias relies on the
      measurements of atrioventricular (AV) and ventriculoatrial (VA) time intervals.
      Pulsed Doppler over in- and outflow of the left ventricle and tissue Doppler
      imaging are well-described methods, while Doppler measurements between the left
      brachiocephalic vein and the aortic arch are less investigated. The aim of this
      study was to compare these methods of measurement, to find influencing factors on
      AV and VA times and their ratio, and to create reference ranges. METHODS:
      Echocardiography was performed between 16 and 40 weeks of gestation in normal
      singleton pregnancies. Nomograms for the individual measurements were created
      using quantile regression with Matlab Data Analytics. Statistical analyses were
      performed with GraphPad version 5.0 for Windows. RESULTS: A total of 329 pregnant
      women were enrolled. A significant correlation exists between AV and VA times and
      gestational age (GA) (p = 0.0104 to <0.0001, sigma = 0.1412 to 0.3632). No
      correlation was found between the AV:VA ratio and GA (p = 0.08 to 0.60). All
      measurements differed significantly amongst the studied methods (p < 0.0001).
      CONCLUSIONS: AV and VA intervals increase proportionally with GA; no other
      independent influencing factors could be identified. As significant differences
      exist between the three methods of assessment, it is crucial to use appropriate
      reference ranges to diagnose pathologies.

PMID- 29045942
TI  - Quantitative Renal Echogenicity as a Tool for Diagnosis of Advanced Chronic
      Kidney Disease in Patients with Glomerulopathies and no Liver Disease.
AB  - BACKGROUND/AIMS: Glomerulopathy patients are prone to developing transitory
      reduced glomerular filtration rate (GFR), which can be difficult to differentiate
      from irreversible chronic kidney disease (CKD). Renal ultrasound can be useful,
      but differently from renal length, quantitative renal echogenicity has not been
      formerly evaluated regarding its capacity to identify irreversible advanced CKD.
      METHODS: A prospective study was performed, where quantitative renal echogenicity
      was performed during renal biopsy in patients with suspected glomerular disease
      (n=197). Quantitative echogenicity was measured as the inverse of the ratio
      between the mean pixel densities of the renal cortex and adjacent liver using
      ScionImage software. Patients were followed during a six-months period to
      ascertain irreversible advanced CKD. Quantitative renal echogenicity and
      histopathology parameters discriminatory capacity were compared regarding their
      capacity to detect advanced and irreversible CKD - estimated GFR less than
      30mL/min/1.73m2 confirmed after a six-month follow-up. RESULTS: At renal biopsy,
      the mean eGFR was 53.9+/-33.6 mL/min/1.73m2 and 63 (32.0%) patients had an eGFR
      less than 30 mL/min/1.73m2. Mean kidney/liver echogenicity ratio was 1.06+/-0.19
      and it was inversely correlated with eGFR at follow-up (r=-0.684, p<0.001).
      Multivariate analysis was performed to create a histopathology index that
      correctly identifies irreversible advanced CKD. Renal echogenicity discriminatory
      capacity to identify irreversible advanced CKD was 0.793 (0.719 -0.867), similar
      to the histopathology index. Elevated renal echogenicity with best discriminatory
      capacity was a kidney/liver ratio greater than 1.15. This cutoff had a predictive
      positive value of 92% in patients with eGFR less than 30mL/min/1.73m2.
      CONCLUSION: Quantitative renal echogenicity can be a useful tool in patients with
      glomerular disease and normal kidney size (>8cm) to identify those patients with
      irreversible advanced CKD.

PMID- 29045944
TI  - Prevalence Estimates of Rare Congenital Anomalies by Integrating Two Population
      Based Registries in Tuscany, Italy.
AB  - BACKGROUND/AIMS: Population-based registries play a key role in the
      epidemiological surveillance of congenital anomalies (CAs). This study is aimed
      at improving the epidemiological surveillance and providing prevalence estimates
      of rare CAs using the Registry of Rare Diseases as an added data source to the
      Registry of Congenital Anomalies. METHODS: Cases of diagnosed rare CAs (2006
      2013) were extracted from the Tuscany Registry of Rare Diseases and the Tuscany
      Registry of Congenital Anomalies in order to set up an integrated dataset.
      Prevalence (per 100,000 births; 95% confidence interval) was calculated for each
      rare CA. RESULTS: Overall, 56 rare CAs were analyzed including 656 cases, of whom
      121 (18.4%) were retrieved from the Registry of Rare Diseases that provided a
      major contribution for rare CAs for which a prenatal diagnosis is difficult, or
      for CAs more easily diagnosed in the postneonatal period. After data integration,
      an increased prevalence estimate was observed in particular for atresia of bile
      ducts (6.24; 3.57-10.14), tuberous sclerosis (2.34; 0.86-5.10), Kabuki syndrome
      (1.95; 0.63-4.55), and some monogenic CAs. CONCLUSIONS: This study represents an
      example of integration of registries operating in the field of rare diseases.
      Providing the accurate prevalence of rare CAs is a key point to improving
      surveillance, supporting public health policies, and planning healthcare.

PMID- 29045946
TI  - Subfoveal Choroidal and Macular Thickness Changes after Phacoemulsification Using
      Enhanced Depth Imaging Optical Coherence Tomography.
AB  - PURPOSE: To assess changes in the thickness of the subfoveal retina and choroid
      after phacoemulsification using enhanced depth imaging optical coherence
      tomography (EDI-OCT). METHODS: A prospective study was conducted on 100 patients.
      The subfoveal choroidal thickness (SFCT) was measured at 7 points and the retinal
      thickness was measured at 5 points (before surgery, and 1 day, 1 week, 1 month,
      and 3 months after surgery). RESULTS: The foveal choroidal thickness showed a
      thickening trend (but p > 0.05). Compared to the change from baseline to day 1,
      the changes from baseline were significantly different at nasal 3 mm and 6 mm at
      all other time points (all p < 0.05). Choroidal thickness changes at temporal 6
      mm correlated negatively with intraocular pressure (IOP) at 1 week and 1 month;
      changes at nasal 3 mm correlated negatively with IOP at 1 week and 1 month (all p
      < 0.05); changes at nasal 3 mm, temporal 3 mm, and temporal 6 mm correlated with
      average ultrasonic energy. Choroidal thickness changes correlated with ultrasound
      (US) time at day 1. CONCLUSIONS: Uncomplicated phacoemulsification led to changes
      in choroidal thickness. IOP and choroidal thickness changes were negatively
      correlated. The foveal retinal thickness was correlated with age. SFCT was
      correlated with sex, axial length, IOP, and US time.

PMID- 29045945
TI  - Retreatment of Exudative Age-Related Macular Degeneration after Loading 3-Monthly
      Intravitreal Ranibizumab.
AB  - PURPOSE: The aim of this study was to investigate the clinical implications of
      required retreatment after 3-monthly intravitreal ranibizumab (IVR) injections
      followed by as-needed reinjections up to 5 years in eyes with exudative age
      related macular degeneration (AMD). METHODS: A retrospective cohort study was
      conducted for 165 treatment-naive eyes from 165 patients with exudative AMD.
      Visual changes were investigated in terms of the required retreatments. RESULTS:
      Retreatment-free proportions were 37.0, 23.7, 16.6, 12.1, and 10.5% at 12, 24,
      36, 48, and 60 months, respectively. Visual changes were significantly better in
      eyes which did not require retreatment at every yearly checkpoint within the 5
      years. A multivariate logistic regression analysis revealed that requirement of
      additional IVR treatments in the first 12-24 months was associated with the T
      allele (risk allele) of ARMS2 A69S (p = 0.010 and 0.015, respectively). Cox
      regression analysis revealed that older age (p = 0.046) and the T allele of ARMS2
      A69S (p = 0.036) were associated with required retreatment within the 5-year
      follow-up period. CONCLUSIONS: Age and the T allele of ARMS2 A69S are the risk
      factors requiring retreatments, leading to poor visual change in eyes with
      exudative AMD following the initial 3-monthly IVR.

PMID- 29045947
TI  - Prediction of the Future Need for Institutional Care in Finnish Older People: A
      Comparison of Two Birth Cohorts.
AB  - BACKGROUND: More recent birth cohorts of older people have better physical and
      cognitive status than earlier cohorts. As such, this could be expected to
      diminish the need for institutional care. The prediction of the future need for
      institutional care provides essential information for the planning and delivery
      of future care and social services as well as the resources needed. OBJECTIVE: To
      predict the future need for institutional care among older Finnish people born in
      1940. METHODS: Representative samples of home-dwelling 70-year-olds from Turku,
      Finland were examined with similar methods in 1991 (those born in 1920) (n =
      1,032) and in 2011 (those born in 1940) (n = 956). Predictors of
      institutionalization rates from the earlier 1920 cohort, together with data of
      sociodemographic factors, health, psychosocial and physical status, the need for
      help, and health behavior, were used to predict the future institutionalization
      rate among the 1940 cohort in this study using Cox regression models. RESULTS:
      Health as well as psychosocial and physical status were significantly better in
      the 1940 cohort compared to the earlier cohort. In the 1940 cohort, the predicted
      rates of institutionalization were 1.8, 10.4, and 26.0% at the ages of 80 (year
      2020), 85 (year 2025), and 90 years (year 2030), respectively. At every age (80,
      85, and 90 years), the predicted rates of institutionalization by Mini-Mental
      State Examination (MMSE) were about two-fold among those with MMSE scores 18-26
      (3.0-38.8%) compared to those with scores 27-30 (1.6-23.7%) and those with a body
      mass index (BMI) <25 (2.5-34.3%) compared to those with a BMI of 25-29.9 (1.4
      20.9%), and about three-fold among participants with several falls (5.3-57.0%)
      compared to participants with no falls (1.5-23.1%). CONCLUSIONS: The 1940 cohort
      performed better in health as well as psychosocial and physical status than the
      1920 cohort. Nevertheless, the predicted rates of future need for institutional
      care were high, especially at the ages of 85 and 90 years, among those with a
      lowered cognitive or physical status.

PMID- 29045948
TI  - Impact of Gastric Cancer Surgery in Elderly Patients.
AB  - OBJECTIVES: This study aimed to investigate the validity of gastric cancer
      surgery in elderly patients. METHODS: A total of 544 patients who underwent
      elective gastrectomy for gastric cancer were divided into an elderly group (age
      >=75 years, n = 171) and a control group (age <75 years, n = 373). The
      clinicopathological data of the patients were reviewed. RESULTS: The overall
      morbidity rate (26.3 vs. 16.1%, p = 0.005) and the incidence rate of anastomotic
      leakage (6.4 vs. 1.6%, p = 0.003) were significantly higher in the elderly group.
      The proportion of patients who had severe complications (>=grade IIIa) was
      relatively higher in the elderly group (10.5 vs. 5.7%); however, the difference
      was not significant (p = 0.074). A stage-matched survival analysis revealed no
      significant differences between the groups (stage I: p = 0.978; stage II: p =
      0.964; stage III: p = 0.199). For the pathological stages II and III, the overall
      survival of the patients in the elderly group who received adjuvant chemotherapy
      for >3 months was significantly better than that of the patients who received it
      for <=3 months or did not receive it (p = 0.023). CONCLUSIONS: An aggressive
      treatment strategy should be adopted in selected elderly patients with gastric
      cancer.

PMID- 29045949
TI  - Effectiveness of a Home-Based Active Video Game Programme in Young Cystic
      Fibrosis Patients.
AB  - BACKGROUND: Exercise-based rehabilitation is already a part of cystic fibrosis
      (CF) treatment; however, patient adherence is low. OBJECTIVES: To assess the
      effectiveness of a home exercise programme using active video games (AVGs) as a
      training modality for children and adolescents with CF. METHODS: Thirty-nine
      children with CF were randomised to a control group (CG, n = 20, age 11 +/- 6
      years; FEV1 86.2 +/- 20.5% of predicted) or a training group (AVGG, n = 19, age
      13 +/- 3 years; FEV1 82.7 +/- 21.7% of predicted). The home training protocol
      consisted of 30- to 60-min sessions, 5 days/week, for 6 weeks using a Nintendo
      WiiTM platform. Exercise capacity was measured by the 6-min walk test (6MWT) and
      modified shuttle walk test (MSWT); muscular strength was estimated using the
      horizontal jump test (HJT), medicine ball throw (MBT), and hand grip strength
      (right [RHG]; left [LHG]); and quality of life was rated using the Cystic
      Fibrosis Questionnaire-Revised (CFQ-R). All the children were measured at
      baseline, after rehabilitation, and at 12 months. RESULTS: For the group * time
      interaction ANOVAs, the AVGG showed significant between-group differences in
      exercise capacity: 6MWT farthest walking distance, 38.4 m (p < 0.01); MSWT
      farthest walking distance, 78.4 m (p < 0.05); and muscular strength: HJT 9.8 cm,
      MBT 30.8 cm, RHG 7 kg, and LHG 6.5 kg (p < 0.01), before versus after
      intervention. The CFQ-R reported significantly higher scores on respiratory
      symptoms after the intervention and favoured the AVGG, and there was an
      improvement in other domains after 12 months. Adherence to the home exercise
      programme was 95% during the 6- week intervention period. CONCLUSION: A home
      based programme using AVGs can effectively improve exercise capacity, muscular
      strength and quality of life in the short-term in children and adolescents with
      CF. The effects of training on muscle performance and quality of life were
      sustained over 12 months.

PMID- 29045950
TI  - Leonurine Prevents Atherosclerosis Via Promoting the Expression of ABCA1 and
      ABCG1 in a Ppargamma/Lxralpha Signaling Pathway-Dependent Manner.
AB  - BACKGROUND/AIMS: Previous studies have demonstrated that leonurine, a unique
      alkaloid compound of Herba leonuri, can exert anti-oxidative and anti
      inflammatory effects on the development of atherosclerosis (AS). This study was
      designed to investigate the effects of leonurine on cholesterol efflux from THP-1
      macrophage-derived foam cells and development of atherosclerotic lesions in apoE
      /- mice, and further determine the potential mechanisms. METHODS: Human THP-1
      cells were fully differentiated into foam cells by the pre-treatment with phorbol
      12-myristate-13-acetate (PMA) and oxidized density lipoproteins (ox-LDL). After
      cells were incubated with various concentrations of leonurine, Oil Red O staining
      and high-performance liquid chromatography (HPLC) assays were utilized to detect
      cellular lipid accumulation and cholesterol content, respectively. Cellular
      cholesterol efflux was determined by liquid scintillation counting. The mRNA and
      protein levels of ATP-binding cassette transporter A1/G1 (ABCA1/G1), peroxisome
      proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha
      (LXRalpha) in foam cells were assessed using real-time quantitative PCR (RT-qPCR)
      and western blot analyses, respectively. Plasma triglyceride (TG), total
      cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and low-density
      lipoprotein-cholesterol (LDL-C) levels in apoE-/- mice were evaluated using
      enzymatic methods. The atherosclerotic lesion sizes and collagen contents in
      aortic roots were determined by Oil Red O and Masson's trichrome staining,
      respectively. RESULTS: Oil Red O staining and liquid scintillation counting
      assays showed that leonurine significantly inhibited lipid accumulation and
      promoted 3H-cholesterol efflux in human THP-1 macrophage-derived foam cells in a
      concentration-dependent manner. Besides, both the mRNA and protein levels of
      ABCA1/G1, PPARgamma and LXRalpha were enhanced by leonurine, which were
      attenuated by LXRalpha siRNA or PPARgamma siRNA transfection. Finally, leonurine
      improved plasma lipid profile, decreased atherosclerotic lesion sizes, increased
      collagen contents and amplified PPARgamma, LXRalpha and ABCA1/G1 expressions in
      aortic roots of apoE-/- mice. CONCLUSIONS: Leonurine can promote cholesterol
      efflux and alleviate cellular lipid accumulation by magnifying the expression of
      ABCA1/G1 in a PPARgamma/LXRalpha signaling pathway-dependent manner in human THP
      1 macrophage-derived foam cells and abate atherogenesis in apoE-/- mice, which
      may offer a promising therapeutic intervention of leonurine in protecting against
      AS.

PMID- 29045951
TI  - Lifestyle Behaviors and Clinical Outcomes in Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: Lifestyle behaviors are not well-characterized in idiopathic
      pulmonary fibrosis (IPF). OBJECTIVES: To assess the association between lifestyle
      behaviors and clinical outcomes in patients with IPF. METHODS: A total of 34 IPF
      patients (median age 68 years) were assessed for daily sitting and weekly walking
      times using the International Physical Activity Questionnaire by in-person
      interview at baseline, and they were followed up for up to 40 months. Cox
      proportional hazard analysis was conducted for cardiorespiratory-related
      hospitalizations and mortality as outcomes. RESULTS: Fifty percent of all
      patients were hospitalized, and 32% died during the follow-up period. Sitting and
      walking times were associated with hospitalizations and mortality in IPF.
      Compared to patients who reported a sitting time of <5 h/day, patients who sat 5
      to <10 and >=10 h/day experienced an increased risk of 2.4 and 5.8 (p trend =
      0.036) for hospitalization and of 4.6 and 21.2 (p trend = 0.018) for mortality,
      respectively. Compared to patients walking <100 min/week, patients with a walking
      time of 100 to <150 and >=150 min/week were associated with a 49 and 74% reduced
      risk for hospitalizations (p trend = 0.022) and a 62 and 86% reduced risk for
      mortality (p trend = 0.018), respectively. The risk for mortality was further
      reduced with a combination of shorter sitting and extended walking times.
      CONCLUSIONS: Shorter daily sitting and longer weekly walking times were
      associated with reduced hospitalization and mortality risks in patients with IPF.
      These findings suggest a clinical importance of assessing lifestyle behaviors in
      a comprehensive evaluation and prognostication of IPF patients. The results
      underscore potential clinical benefits of reducing sedentary behaviors among IPF
      patients; however, this warrants further investigation.

PMID- 29045952
TI  - [Progress in diagnosis and management of syncope in children].
AB  - Syncope is a common emergency of children and adolescents, which has serious
      influence on the quality of life. Neurally-mediated syncope, including postural
      tachycardia syndrome, vasovagal syncope, orthostatic hypotension and orthostatic
      hypertension, is the main cause of syncope in children and adolescents. The main
      manifestations of neurally-mediated syncope are diverse, such as dizziness,
      headache, chest tightness, chest pain, pale complexion, fatigue, pre-syncope and
      syncope. Although the clinical manifestations are similar, each subtype of
      syncope has its hemodynamic feature and optimal treatment option. The diagnosis
      rate of syncope in children has been greatly improved on account of the
      development of the diagnostic procedures and methods. In recent years, with the
      promotion of head-up tilt test and drug-provocated head-up tilt test, the
      hemodynamic classification of neurally-mediated syncope gets continually refined.
      In recent years, with the effort of clinicians, an appropriate diagnostic
      protocol for children with syncope has been established. The initial evaluation
      consists of history taking, physical examination, standing test and standard
      electrocardiography. After the initial evaluation, some patients could be
      diagnosed definitely, such as postural tachycardia syndrome, orthostatic
      hypotension, and situational syncope. Those with a specific entity causing
      syncope need selective clinical and laboratory investigations. Patients for whom
      the cause of syncope remained undetermined should undergo head-up tilt test. The
      precise pathogenesis of neurally-mediated syncope is not entirely clear. In
      recent years, studies have shown that neurally-mediated syncope may be related to
      several factors, including hypovolemia, high catecholamine status, abnormal local
      vascular tension, decreased skeletal muscle pump activity and abnormal
      neurohumoral factors. Currently based on the possible pathogenesis, the
      individualized treatment of neurally-mediated syncope has also been studied in
      depth. Generally, the management of neurally-mediated syncope includes non
      pharmacological and pharmacological interventions. Patient education is the
      fundamental part above all. In addition to exercise training, the first-line
      treatments mainly include oral rehydration salts, beta adrenoreceptor blockers,
      and alpha adrenoreceptor agonists. By analyzing the patient's physiological
      indexes and biomarkers before treatment, the efficacy of medication could be well
      predicted. The individualized treatment will become the main direction in the
      future researches.

PMID- 29045953
TI  - [Detection of large deletions in X linked Alport syndrome using competitive
      multiplex fluorescence polymerase chain reaction].
AB  - OBJECTIVE: To evaluate the ability of multiplex competitive fluorescence
      polymerase chain reaction in detection of large deletion and duplication
      genotypes of X-linked Alport syndrome. METHODS: Clinical diagnosis of X-linked
      Alport syndrome was based on either abnormal staining of type IV collagen alpha5
      chain in the epidermal basement membrane alone or with abnormal staining of type
      IV collagen alpha5 chain in the glomerular basement membrane and Bowman's
      capsule/ultrastructural changes in the glomerular basement membrane typical of
      Alport syndrome. A total of 20 unrelated Chinese patients (13 males and 7
      females) clinically diagnosed as X-linked Alport syndrome were included in the
      study. Their genotypes were unknown. Control subjects included a male patient
      with other renal disease and two patients who had large deletions in COL4A5 gene
      detected by multiplex ligation-dependent probe amplification. Genomic DNA was
      isolated from peripheral blood leukocytes in all the participants. Multiplex
      competitive fluorescence polymerase chain reaction was used to coamplify 53 exons
      of COL4A5 gene and four reference genes in a single reaction. When a deletion
      removed exon 1 of COL4A5 gene was identified, the same method was used to
      coamplify the first 4 exons of COL4A5 and COL4A6 genes, a promoter shared by
      COL4A5 and COL4A6 genes, and three reference genes in a single reaction. Any copy
      number loss suggested by this method was verified by electrophoresis of
      corresponding polymerase chain reaction amplified products or DNA sequencing to
      exclude possible DNA variations in the primer regions. RESULTS: Genotypes of two
      positive controls identified by multiplex competitive fluorescence polymerase
      chain reaction were consistent with those detected by multiplex ligation
      dependent probe amplification. Deletions were identified in 6 of the 20 patients,
      including two large deletions removing the 5' part of both COL4A5 and COL4A6
      genes with the breakpoint located in the second intron of COL4A6, two large
      deletions removing more than 30 exons of COL4A5 gene, one large deletion removing
      at least 1 exon of COL4A5 gene, and one small deletion involving 13 bps. No
      duplication was found. CONCLUSION: Our results show that multiplex competitive
      fluorescence polymerase chain reaction is a good alternative to classical
      techniques for large deletion genotyping in X-linked Alport syndrome.

PMID- 29045954
TI  - [Pulmonary arterial hypertension as leading manifestation of methylmalonic
      aciduria: clinical characteristics and gene testing in 15 cases].
AB  - OBJECTIVE: To deepen our understanding of Methylmalonic aciduria (MMA) associated
      pulmonary hypertension (PH) by analyzing the characteristics of clinical
      presentation, pulmonary high resolusion CT(HRCT), treatment response and gene
      mutation. METHODS: This study includes 15 cases of pediatric patients with MMA
      associated PH diagnosed and treated in Peking University First Hospital pediatric
      department between May 2012 and May 2016 with symptoms of PH as their leading
      presentation. Clinical symptoms and signs were recorded, Routine blood laboratory
      examinations was done including arterial blood gas analysis. Plasma total
      homocysteine (Hcy) and brain natriuretic peptide(BNP) level were measured. MMA
      gene mutation was analyzed. Chest HRCT was done in most of the patients. Standard
      treatment strategy to MMA and PH was given and follow up study was done, and the
      related literature was reviewed. Statistical analysis was done. The diagnosis of
      MMA was made by methylmalonic acid level >100 times the normal value in the
      urine. The diagnosis of PH was made by pulmonary arterial systolic pressure
      (PASP)>40 mmHg, which was estimated by the measurement of tricuspid regurgitation
      velocity through Doppler Echocardiography. RESULTS: (1) Patient characteristics:
      There were 10 male and 5 female patients diagnosed as MMA associated PH, aged 0.5
      to 13.8 years, with an average of (5.0+/-4.3) years. The age of onset of PH was
      (3.7+/-3.5) years, with an early onset type MMA in 5 cases and late-onset type in
      10 cases. (2) Clinical presentation: Among the 15 cases of MMA, the first
      symptoms were associated with PH in 10 cases, so PH and MMA were diagnosed at the
      same time, and PH was diagnosed 3 to 72 months post MMA presentation in the other
      5 cases. The main presentations of PH were techypnea/dyspnea and cyanosis in 11
      cases each, weakness and fatigue on exertion in 6 cases, and edema in 4 cases. PH
      WHO functional classification (WHO FC) was Class II in 4 , Class III in 5 and
      Class VI in 6 cases, with an average of Class 3.1+/-0.8. Multi-system
      involvements were common with the highest frequency in the kidney (14 cases).
      Macrocytic anemia was present in 8 cases and sub-clinical hypothyroidism in 5
      cases, and mild to moderate mental retardation in 4 cases. (3) Laboratory
      examination: PASP of the 15 patients was from 49 to 135 mmHg, with an average of
      (90.3+/-23.9) mmHg. Total blood Hcy level was severely elevated to (121.2+/-48.2)
      MUmol/L (range: 35.0-221.0 MUmol/L), and Hcy >100 MUmol/L within 11 cases. Plasma
      BNP level was also elevated, median 794 ng/L (range: 21.0-4 995.0 ng/L) with 12
      cases >300 ng/L. Blood gas analysis showed low arterial blood oxygen saturation
      between 70% and 94%, with an average of 81.4%+/-8.4%. (4) Chest HRCT: chest HRCT
      showed a diffuse ground-glass centrilobular nodular opacities with septal line
      thickening in the lungs in 9 cases, and with associated mediastinal lymph node
      enlargement in 1 case, which indicated pulmonary veno-occlusive disease (PVOD), a
      rare type of pulmonary arterial hypertension (PAH). There was lung infection or
      edema in 3 cases, and interstitial infiltration and mesh-like feature in other 3
      cases, which was inferred to interstitial lung disease. (5) Gene mutation:
      Genetic testing was done in 10 cases, totally 5 reported disease-causing
      mutations were found. There were 100% presence of MMACHC c.80A>G mutation in all
      the 10 patients tested, with the allelic genes of c.609G>A mutation in 6
      patients, including a sister and a brother from the same parents. (6) Treatment
      and follow up: Intramuscular hydroxocobalamin or vitamin B12 was given to all of
      the patients, together with betaine, levocarnidtine, folinic acid and vitamin B6.
      According to the severity of PH, single or combined PAH targeted drugs was given
      to 11 cases. By an average of (20.0+/-13.5) days of in-hospital treatment in 13
      patients (excepting 1 case treated as outpatient), symptoms remarkably resolved,
      WHO FC reduced to an average of Class 2.4+/-0.9, PASP dropped to (69.4+/-21.3)
      mmHg, and plasma Hcy and BNP level were decreased to (74.9+/-25.9) MUmol/L and
      (341.6+/-180.2) ng/L, respectively. The above values all reached statistical
      significance (P<0.05) compared with each related value before treatment. There
      were 2 patients who expired during hospitalization despite of treatment. At the
      end of 3 months' follow up, all of the 13 patients disposed oxygen, and PASP
      significantly dropped to 38.7+/-7.9 mmHg, and plasma BNP returned to normal, but
      plasma Hcy level showed no further decline. At the last follow up of 27.5+/-19.0
      (range: 11-64) months, all the patients' PASP remained normal except for the 13.8
      year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH
      still having PASP 58 mmHg. CONCLUSION: PH is a severe complication of MMA
      combined type, especially cblC type, it is more often happens in late-onset type
      of male patients and can be the first and leading manifestations of MMA. Its
      clinical symptoms are urgent and severe, characterized by tachypnea/dyspnea and
      cyanosis, and sometimes right heart failure, hypoxemia is usually present, chest
      HRCT is often indicative of PVOD, lung edema and interstitial lung disease may
      occur. Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH
      medication can reverse PH and save life. MMACHC gene c.80A>G mutation may be the
      hot point of MMA cblC type associated PH.

PMID- 29045955
TI  - [Comparison between continuous noninvasive hemoglobin monitoring and venous blood
      hemoglobin monitoring in children with kidney disease].
AB  - OBJECTIVE: To assess the correlation and consistency between continuous
      noninvasive hemoglobin detection and venous blood hemoglobin detection in
      children with kidney disease, and try to analyze the affecting factors. Try to
      provide a reference for the monitoring of hemoglobin in children with kidney
      disease by continuous noninvasive hemoglobin detection technique. METHODS: Eighty
      five inpatient children with kidney disease, 50 boys (58.8%) and 35 girls
      (41.2%), aged from 3 years old to 18 years old (9.35+/-4.29) were included
      finally. Noninvasive hemoglobin monitoring by spectrophotometry (SpHb) was stably
      read by PRONTO-7, selecting the ring finger of the non handedness as the
      detection site. And then the venous blood hemoglobin of the same patient was
      collected in 5 minutes as the true hemoglobin (tHb) by Beckman coulter DXH-800.
      The data of SpHb and tHb were compared and analyzed using SPSS 17.0 and MedCalc.
      RESULTS: Correlation analysis showed data of SpHb and tHb were with significant
      correlation, the correlation coefficient between SpHb and tHb was 0.85 (P<0.05).
      Bland-Altman plot points suggested that the mean of differences between SpHb and
      tHb was -1.3 g/dL. The 95% CI of agreement of SpHb-tHb was -4.2-1.5 g/dL,
      suggesting that the average measurement result of SpHb was lower than that of
      tHb. The mean of differences as percent between SpHb and tHb was -9.8%, 95% CI of
      agreement was (-35.9%, 16.2%) exceeding the acceptable range of true value +/-6%.
      The consistent rate of non-invasive hemoglobin detection and venous blood
      hemoglobin detection was 31.8%, the 95% CI of consistent rate was (21.7%, 41.9%).
      The chi square test of the fourfold table showed that the diagnosis of anemia
      with SpHb was of high sensitivity, but the specificity was low, the false
      positive rate was high, and the difference was statistically significant
      (P=0.000). CONCLUSION: There was a significant correlation between SpHb and tHb
      in the children with kidney disease. Noninvasive hemoglobin measurement can be
      used for monitoring of changes of hemoglobin in children with kidney diseases.
      But the consistency between SpHb and tHb needs to be improved. Noninvasive
      hemoglobin measurement could not replace the venous hemoglobin measurement. It
      could not be used for the diagnosis of anemia, and the accuracy of hemoglobin
      concentration measurement in children with kidney disease should be further
      explored.

PMID- 29045956
TI  - [Co-morbidity of vasovagal syncope and postural tachycardia syndrome with
      allergic diseases in children].
AB  - OBJECTIVE: To explore the clinical characteristics of the co-morbidity of
      vasovagal syncope (VVS) and postural tachycardia syndrome (POTS) with allergic
      diseases in children. METHODS: A re-trospective analysis was launched to
      summarize the clinical data of children with VVS and POTS. They were divided into
      allergic group and non-allergic group according to the history of allergic
      diseases. The participants' clinical characteristics were compared between
      allergic group and non-allergic group using independent sample t test or rank sum
      test; composition comparisons were completed by Chi-square test. Bi-variate
      correlation analysis was used to explore the association between eosinophil
      percentage/count and symptom scores/frequency of syncope episodes. A P value
      <0.05 was defined as statistically significant. RESULTS: Sixty-seven children
      complaining of orthostatic intolerance (43 patients diagnosed as VVS and 24 cases
      diagnosed as POTS) were enrolled. Totally 21 cases (31%) had allergic diseases,
      including allergic rhinitis, atopic eczema, asthma, as well as food allergy. And
      allergic rhinitis is the most common co-morbidity. There were no significant
      differences between the two groups in age, gender ratio, height, body weight and
      basement blood pressure. Compared with the non-allergic group, the allergic group
      showed later onset age (year) (11+/-2 vs. 9+/-3, P<0.05) of orthostatic
      intolerance and shorter course of the diseases (month) [8.0 (0.1, 0.1) vs. 24.0
      (0.1, 144.0), P<0.05]. The frequency of syncope episodes in the allergic group
      among VVS children (times per month) [2.50 (0.08, 30.00) vs. 0.25 (0.03, 5.00),
      P<0.05] was much higher than that in the non-allergic group. Additionally, the
      eosinophil percentage (%) [3.50 (0.70, 0.59) vs. 1.65 (0.30, 6.20), P<0.001] and
      eosinophil count (*109) [0.18 (0.05, 0.71) vs. 0.10 (0.02, 0.38), P<0.001] were
      increased in the allergic group. However, there were no remarkable differences in
      the results of head-up tilt test in children with VVS or in the maximum change of
      heart rate during standing test in children with POTS were involved. CONCLUSION:
      Allergic diseases are common co-morbidities in children with both VVS and POTS.
      Allergic rhinitis is the most common co-morbidity. Children with co-morbidity of
      VVS/POTS and allergic diseases had a later onset of symptoms of orthostatic
      intolerance, and were more likely to be hospitalized for intensive attacks of
      symptoms during a short period when compared with those without allergic
      diseases. Children diagnosed as VVS combined with allergic diseases had more
      frequent episodes of syncope.

PMID- 29045957
TI  - [Clinical characteristics of neonatal fungal sepsis in neonatal intensive care
      unit].
AB  - OBJECTIVE: To study the characteristics of neonatal fungal sepsis and the
      difference between bacterial sepsis and fungal sepsis. To improve the
      understanding of neonatal fungal sepsis. METHODS: Clinical data of neonatal
      fungal sepsis in neonatal intensive care unit (NICU) were collected from 2011 to
      2016 in Peking University first Hospital. The clinical characteristics were
      analyzed retrospectively. The difference between neonatal fungal sepsis and
      bacterial sepsis was also analyzed. RESULTS: Fifteen cases of neonatal fungal
      sepsis were recruited. Over the study period, the incidence of neonatal fungal
      sepsis was 0.52%, while it was 2.5% in very low birth weight infants. Clinical
      characteristics were nonspeci-fic. All the infants were treated with parenteral
      nutrition and broad spectrum antibiotics. Peripheral inserted central catheter
      (PICC) was placed in thirteen patients. Pathogenic analyses indicated Candida
      glabrata was the main pathogen in our study. All the pathogens were sensitive to
      amphotericin B. Only one Candida glabrata was resistant to fluconazole. Thirty
      four cases of bacterial sepsis were included. The clinical characteristics and
      laboratory examination results were compared. The platelet count was 61*109/L in
      fungal group, while the platelet count was 178*109/L in bacterial group. There
      was statistical difference between the fungal group and bacterial group
      (P=0.004). The rate of thrombocytopenia was 80.0% in fungal group, while it was
      29.4% in bacterial group. It was much higher in fungal group than in bacterial
      group (P=0.001). The rate of PICC placement was 86.7% in fungal group, while it
      was 55.7% in bacterial group. It was much higher in fungal group than in
      bacterial group (P=0.037). Receiver operating characteristic (ROC) curve analysis
      showed that the cut-off value of the platelet count for the diagnosis of neonatal
      fungal sepsis was 145*109/L (sensitivity 61.8%, specificity 92.9%). All the
      patients were cured after standardized antifungal therapy. The indicators of
      liver and renal function were also measured before and after antifungal therapy.
      No significant difference was observed before and after treatment. CONCLUSION:
      The clinical characteristics of neonatal fungal sepsis was nonspecific. Candida
      glabrata was the main pathogen in our NICU. It can be cured as the result of
      standardized treatment. Decreased platelet count and PICC placement may indicate
      the possibility of fungal sepsis in neonates.

PMID- 29045958
TI  - [Clinical characteristics of glucocorticoid-induced eye adverse reactions in
      children with primary nephrotic syndrome].
AB  - OBJECTIVE: To investigate the clinical features and side effects, with regard to
      glucocorticoid-induced ocular hypertension, glaucoma or cataract in children with
      primary nephrotic syndrome. METHODS: Clinical data were collected and analyzed
      from 71 cases of primary nephrotic syndrome with glucocorticoid-induced ocular
      hypertension, glaucoma or cataract from Jun. 2014 to Jun. 2016. These children
      were hospitalized in Peking University First Hospital. RESULTS: Totally 1 580
      children with primary nephrotic syndrome were collected, glucocorticoid-induced
      complications in eyes were found in 71 cases, and the incidence was 4.5%. There
      were 66 cases with ocular hypertension, 2 cases with glucocorticoid glaucoma, 2
      cases with glucocorticoid glaucoma combined with cataract, 1 case with high
      intraocular pressure combined with cataract. There were 41 boys and 30 girls with
      eye-related side effects caused by glucocorticoid. The average age of onset of
      glucocorticoid-induced eye adverse reactions in children with primary nephrotic
      syndrome in our research were 8 (2, 16) years. The average duration or interval
      time from glucocorticoid medication use to eye adverse effects was 157 (6, 420)
      days. No statistical significance was found in intraocular pressure between
      different genders, types of glucocorticoid, different route of glucocorticoid and
      whether methylprednisolone pulse treatment (P>0.05). There was no significant
      correlation between age, body mass index, blood pressure, cumulative dosage,
      duration time of glucocorticoid, mean daily dosage and glucocorticoid-induced
      ocular hypertension (P>0.05). The ocular hypertension was controlled after
      treatment. CONCLUSION: Children with nephrotic syndrome after treatment of
      glucocorticoid are susceptible to ocular complications, and the occurrence of
      ocular hypertension is closely related to glucocorticoid susceptibility of the
      nephrotic children. Regular eye monitor is indispensable for the children
      suffering from primary nephrotic syndrome.

PMID- 29045959
TI  - [Prevalence of autism spectrum disorders in children aged 0-6 years in China: a
      meta-analysis].
AB  - OBJECTIVE: To estimate the prevalence and trend of autism spectrum disorders
      (ASD) in children aged 0-6 years in China. METHODS: Systematic literature
      searches were conducted in PubMed, Web of Science, Scopus, China National
      Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM),
      Wanfang and Weipu Database (VIP ), and the literatures published before February
      25, 2017 were selected according to the same criteria. Prevalence Data of three
      periods were abstracted, then pooled using random effect model. Subgroup analysis
      was done across data resource, age group, screening criteria, diagnostic
      criteria, and literature quality. RESULTS: In the study, 9 ASD studies and 20
      autism (also known as autistic disorder, AD) studies were eligible for review.
      The pooled prevalence of AD in children aged 0-6 years in 2006-2010 and 2011-2015
      was 1.74 0/00 (95%CI: 1.120/00-2.690/00) and 1.800/00 (95%CI: 1.330/00-2.430/00),
      and there was no significant difference between the two groups (P=0.898), but
      they were higher than 0.940/00 (95%CI: 0.670/00-1.330/00) in 1996-2005 (P=0.031;
      P=0.005) significantly. The pooled prevalence of ASD in children aged 0-6 years
      was 3.52 0/00 (95% CI: 1.480/00-8.340/00) and 3.480/00 (95%CI: 1.770/00-6.840/00)
      in 2006-2010 and 2011-2015, respectively, and the difference between the two
      periods was not significant (P=0.983). There was no significant difference
      between the pooled prevalence in the three periods among the boys, and girls'
      too. The pooled prevalence of ASD in children aged 0-6 years was 3.510/00 (95%CI:
      2.150/00-5.740/00) and AD was 1.770/00 (95%CI: 1.400/00-2.240/00) in 2006-2015,
      with prevalence ratios of boys to girls 2.59:1 and 3.63:1, respectively. The
      pooled prevalence of AD was lower in 0-6 years children than in other age groups
      and higher in high-quality studies than in low-quality studies, which was the
      same as ASD. Data resource, screening and diagnostic criteria were not
      significantly related with the pooled prevalence of AD and ASD. CONCLUSION: The
      prevalence of ASD and AD in children aged 0-6 years in China from 2006 to 2015
      was stable, and there was not enough evidence to prove that it was higher than
      before 2005. National survey and monitoring of early childhood autism should to
      be conducted.

PMID- 29045960
TI  - Pharmacokinetics of once daily prolonged-release formulation of tacrolimus in
      children with primary nephrotic syndrome.
AB  - OBJECTIVE: Tacrolimus prolonged-release(PR) formulation is a new once-daily
      formulation of the calcineurin inhibitor tacrolimus, which is currently used in
      adult liver or kidney transplant patients,and is also gradually widely used in
      children with nephrotic syndrome.The present study was undertaken to
      preliminarily investigate the pharmacokinetic characteristics of tacrolimus PR in
      pediatric nephrotic syndrome recipients. METHODS: This single-center open-label
      prospective study was performed in pediatric nephrotic syndrome recipients.
      Pharmacokinetic samples were collected from eight pediatric subjects with
      nephrotic syndrome from Department of Pediatric Nephrology in Peking University
      First Hospital between June and August 2011. They followed administration of
      single oral doses of tacrolimus PR formulation at 0.02 mg/kg (n=2), 0.05 mg/kg
      (n=2) and 0.10 mg/kg (n=4). Blood samples were taken before the dose and 1, 2, 4,
      6, 8, 10, 12 and 24 h after drug intake. No other medicines or interacting food
      or drinks were taken during the study period. Blood concentrations were measured
      using an enzyme multiplied immunoassay technique. Pharmacokinetic analysis was
      performed using WinNolin Phoenix software Version 6.0(Pharsight, Cary, NC,USA).
      RESULTS: The pharmacokinetic data were best described by a non-compartment model.
      Pharmacokinetic parameters of tacrolimus PR formulation in the 3 ascending doses
      groups (0.02 mg/kg,0.05 mg/kg and 0.10 mg/kg) were as follows: the maximum drug
      concentrations (Cmax/D) were (1.7+/-1.0) MUg/L, (3.1+/-1.9) MUg/L, (8.0+/-3.5)
      MUg/L, respectively; Areas under the drug concentration-time curve(AUC0
      infinity/D) were (47.2+/-47.1) h*MUg/L, (84.0+/-13.1) h*MUg/L, (175.6+/-107.1)
      h*MUg/L, respectively; Oral clearance rates were (0.8+/-0.9) L/(h*kg), (0.4+/
      0.1) L/(h*kg), (1.9+/-1.3) L/(h*kg), respectively; Body weight normalized
      distribution volumes were (7.0+/-3.4) L/kg, (12.4+/-8.4) L/kg and (73.6+/-68.6)
      L/kg, respectively. Both mean Cmax normalized level for the administered
      dose(Cmax/D) and mean AUC0-infinity normalized level for the administered dose
      (AUC0-infinity/D) were higher in the 0.05 mg/kg dosage group than in the 0.02 and
      0.10 mg/kg dosage group. There were two peaks in the drug concentrations in every
      dose group;a primary peak appeared at the end of about 2 h followed by a small
      secondary peak at h 12, which was more noticeable in the 0.10 mg/kg dose group
      than in the two lower dosages. CONCLUSION: The pharmacokinetic characteristics of
      tacrolimus PR formulation were initially explored in pediatric patients with
      nephritic syndrome. The data presented form a basis for subsequent larger scale
      studies on pharmacokinetics of tacrolimus PR formulation in nephritic syndrome
      children.

PMID- 29045961
TI  - [Effects of recent upper respiratory-tract infections on incidence of the
      perioperative respiratory adverse events in children: a prospective cohort
      study].
AB  - OBJECTIVE: To investigate the effects of the recent upper respiratory tract
      infections (URI) on the incidence of perioperative respiratory adverse events in
      children scheduled to undergo general anesthesia and elective surgery. METHODS:
      In the study, 232 children undergoing general anesthesia with laryngeal mask
      airway (LMA) for elective ophthalmic surgeries at Peking University First
      Hospital, Beijing, China, from Nov. 1, 2015 to May 10, 2016 were enrolled. On the
      day of the surgery, the parents of the children were preoperatively asked to fill
      out a questionnaire regarding the baseline characteristics and medical history of
      the children, including gender, age, height, weight, history of URI within the
      last 2 weeks before anesthesia, history of premature, long-term passive smoking
      exposure, habitual sleep snoring, and history of asthma. In addition, all adverse
      respiratory events throughout the perioperative periods (oxygen desaturation,
      cough, copious secretions, laryngospasm and bronchospasm) as well as peri
      operative variables (number of attempts to insert the LMA successfully,
      anesthesia duration and so on) were recorded. Multivariate Logistic regression
      analysis was applied to identify independent risk factors of perioperative
      respiratory adverse events. RESULTS: Among the 232 children included in the
      study, 28.0% (65/232) presented with a history of a recent URI within the last 2
      weeks before anesthesia. The presence of the recent URI increased the incidence
      of oxygen desaturation (23.1% vs.12.0%, P=0.034), copious secretions (15.4% vs.
      6.6%, P=0.036) and any of all the adverse respiratory events (32.3% vs. 18.6%,
      P=0.024). Multivariate Logistic regression analysis identified two independent
      risk factors of perioperative adverse respiratory events: a history of URI within
      the last 2 weeks before general anesthesia (OR=2.021, 95%CI: 1.023-3.994,
      P=0.043) and habitual sleep snoring (OR=3.660, 95%CI: 1.517-8.832, P=0.004).
      CONCLUSION: A history of a recent URI within 2 weeks before general anesthesia
      was associated with a higher incidence of oxygen desaturation, copious secretions
      and the overall respiratory adverse events. For the children with recent URI, we
      recommend the general anesthesia and elective surgery should be postponed for at
      least 2 weeks after the URI.

PMID- 29045962
TI  - [Myeloid-derived suppressor cells promoted autologous B cell proliferation in
      rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the effect of myeloid-derived suppressor cells (MDSC)
      on pro-liferation of B lymphocytes in rheumatoid arthritis (RA) patients.
      METHODS: The peripheral blood specimens were collected from 15 healthy adults and
      38 RA patients who were divided into high disease activity group, medium activity
      group and low activity group according to their 28-joint disease activity score
      (DAS28). And the frequencies of MDSC were determined by flow cytometry. Then, B
      cells and MDSC were isolated by flow cytometry, respectively. B cells were
      labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) and then were
      co-cultured with MDSC in the presence of 3 mg/L anti-CD40 antibody and 10 mg/L
      CpG, for 3 days. Flow cytometry was performed to investigate the proliferation of
      B cells. RESULTS: MDSC expanded markedly in high disease activity patients (7.13%
      +/-2.17%) compared with medium (5.35%+/-1.36%) and low disease activity patients
      (4.72%+/-1.08%) or healthy controls (4.79%+/-1.02%) (P<0.05), and there were no
      statistical differences between healthy controls, medium and low disease activity
      RA (P>0.05). Moreover, the frequencies of MDSC were positively correlated with
      the DAS28 (P<0.05). After co-culture, MDSC significantly promoted B cell
      proliferation (P<0.01). CONCLUSION: Our studies showed that MDSC expanded
      obviously in high disease activity RA patients, and their frequencies were
      positively correlated with the disease activities. Furthermore, MDSC could
      promote autologous B cell proliferation remarkably in vitro. These findings
      suggest that MDSC might be involved in RA pathogenesis through regulating B cell
      functions.

PMID- 29045963
TI  - [Tumor derived IgG suppress the proliferation of T cells in cord blood].
AB  - OBJECTIVE: To explore the function of tumor derived IgG (tIgG) and whether the
      tIgG can inhibit T cells activity. METHODS: The tIgG was purified from ovarian
      cancer tissue. The cord blood monocyte cells (CBMC) and cord blood lymphocyte
      (CBL) were isolate from human umbilical cord blood. The CBMC and CBL were
      stimulated with phytohaemagg lutinin (PHA) in order to let the CBMC and CBL in
      the state of proliferation. Carboxyfluorescein succinimidyl amino ester (CFSE)
      was cultured with CBMC and CBL. CFSE had no cell toxicity, which could penetrate
      through the cell membrane and combine the intracellular protein. The fluorescence
      intensity decreased with the proliferation of cells step by step, so the
      proliferation of these cells could be detected in flow ctytometry. The tIgG which
      was purified from ovarian cancer tissue was divided into three groups, 1 mg/L
      group, 10 mg/L group, and 100 mg/L group, and the intravenous immunoglobulin
      (IVIG) was also divided into three groups too. The CBMC and CBL were treated by
      tIgG with 1 mg/L, 10 mg/L, and 100 mg/L in order to observe the proliferation of
      T cells. The cells were treated with IVIG as a positive control group, and the
      cells were treated with phosphate buffer saline (PBS) as a negative control. The
      proliferation of CD4+ or CD8+ T cells were detected in CBMC and CBL. The
      proliferation of the T cells in CBMC and CBL after 64 h and 86 h were detected.
      RESULTS: In the system of CBMC, the tIgG could suppress the proliferation of CD4+
      or CD8+ T cells. The results could also be found in the system of CBL. The CD4+
      or CD8+ T cells in the group which were treated with PBS were more active than
      those in the group which were treated with tIgG and IVIG. The suppression in the
      group which were treated with tIgG, was stronger than that in the group treated
      with IVIG. In addition, the suppression of T cells in the group which were
      stimulated with tIgG as 100 mg/L was more effective than that in the group which
      were stimulated with tIgG as 10 mg/L. This could prove that tIgG had the function
      of immunomodulation. CONCLUSION: The tIgG can be involved in immune escape of
      cancer.

PMID- 29045964
TI  - [Increased serum C-C chemokine ligand 19 levels correlated with B cell
      abnormalities in systemic lupus erythematosus].
AB  - OBJECTIVE: To detect the levels of serum C-C chemokine ligand 19 (CCL19) in
      patients with systemic lupus erythematosus (SLE) and to evaluate the correlation
      between CCL19 expression and clinical features and laboratory parameters, trying
      to reveal the possible role of CCL19 in the pathogenesis of systemic lupus
      erythematosus. METHODS: The levels of serum CCL19 were measured by enzyme linked
      immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls.
      These SLE patients included 75 patients who received treatment with
      glucocorticoids and disease-modifying anti-rheumatic drug (DMARD) and 15 patients
      without therapy. The frequencies of peripheral blood B cells and the B cell
      subsets were assessed in the patients with SLE by flow cytometry. The correlation
      between the clinical data, laboratory parameters, B cell subset frequencies and
      serum CCL19 levels were analyzed. Indepen-dent samples t test, paired t test,
      Pearson and Spearman correlation were used for statistical analyses. RESULTS: The
      levels of CCL19 were markedly higher in the SLE patients without therapy and the
      patients with therapy than in the health controls[(596.25+/-409.19) ng/L and
      (422.90+/-395.84) ng/L vs. (157.79+/-125.23) ng/L, all P<0.001]. Serum CCL19
      levels in the SLE patients without therapy were higher than the SLE patients who
      accepted glucocorticoids and DMARD treatment (P<0.05). The levels of serum CCL19
      were positively correlated with anti-double stranded deoxyribonucleic acid
      (dsDNA), anti-nucleosome antibody (AnuA), IgA, IgG and IgM (r=0.38, P=0.007;
      r=0.332, P=0.029; r=0.519, P=0.007; r=0.461, P=0.018, respectively). Serum CCL19
      levels in the SLE patients with photosensitivity, arthritis and secondary
      Sjogren's syndrome were higher than the SLE patients without photosensitivity,
      arthritis and secondary Sjogren's syndrome, respectively [(562.25+/-399.12) ng/L,
      (565.6+/-435.24) ng/L and (694.9+/-531.02) ng/L vs. (394.7+/-281.42) ng/L,
      (385.90+/-325.33) ng/L and (424.8+/-305.46) ng/L, all P<0.05]. The levels of
      serum CCL19 were positively correlated with the percentage of CD27-B cells and
      CD27-IgD-double-negative memory B cells (r=0.519, P=0.007; r=0.461, P=0.018,
      respectively). However, the levels of serum CCL19 were negatively correlated with
      the percentage of CD27+ memory B cells and CD27+IgD- switched memory B cells (r=
      0.433, P=0.027; r=-0.616, P=0.001, respectively). CONCLUSION: The increased serum
      CCL19 levels in SLE patients were associated with the production of
      autoantibodies, and CCL19 might be involved in the pathogenesis of SLE by
      disturbing the homeostasis of B cell subsets.

PMID- 29045965
TI  - [Cause analysis of spinal surgery in ankylosing spondylitis].
AB  - OBJECTIVE: To investigate the common cause of spinal surgery in ankylosing
      spondylitis (AS) and to develop reasonable and effective treatment programs for
      rhematologists. METHODS: In this study, 79 AS patients (72 males, 7 females)
      hospitalized in the Department of Orthopedic and received spinal surgery in
      Peking University Third Hospital from January 2007 to July 2013 were investigated
      retrospectively. The causes of the spinal surgery were analyzed. RESULTS: The
      majority of the surgery were of cervical vertebra surgery for 59 cases (74.7%),
      followed by the thoracolumbar vertebra, thoracic vertebra, cervicothoracic
      vertebra, and lumbar vertebra. The common causes of AS spinal surgery were
      instability (53.2%) including fracture and dislocation caused by trauma mostly,
      followed by compression symptoms (34.1%). However, the orthopaedic surgery
      (12.7%) was not the predominant surgery causes. The most common cause of cervical
      surgery was cervical spondylosis (25 cases), followed by cervical fracture (22
      cases) and cervical dislocation (10 cases). For cervical fracture, the most
      common site was C7 (8 cases). Atlanto-axial vertebral lesions (13 cases) induced
      by dislocation, subluxation, instability and fracture were common in cervical
      vertebra surgery. The age and disease duration of atlantoaxial surgical patient's
      were less than other parts of the cervical surgery. Thoracolumbar vertebra
      surgery included thoracolumbar kyphosis orthopaedic surgery (10 cases), and
      fractures (6 cases), which mainly occurred in T11-12 vertebrae. According to the
      time of admission for surgery, the cases of AS that received spinal surgery were
      34 from 2007 to 2008. The number of the cases that accepted the surgery decreased
      gradually year by year. CONCLUSION: The majority surgery section was cervical
      vertebra, and atlanto-axial vertebral lesions were not rare as we thought. The
      main etiology of spinal surgery for AS patients was instability, e.g. fracture
      and compression symptoms. Of course, trauma accounted for the relative percentage
      of this phetonomenon. Although, the annual number of patients who receives spinal
      surgery is decreasing, to go to make early diagnosis and treatment, and to
      standardize patient education for AS patients are still important.

PMID- 29045966
TI  - [Immune effects of specific CTLs response induced by dendritic cells pulsed with
      NY-ESO-1 peptide].
AB  - OBJECTIVE: To explore the potential of autologous dendritic cells (DCs) pulsed
      with caner/testis antigen NY-ESO-1 peptides in inducing specific cytotoxic T
      lymphocyte (CTLs) response and antineoplastic immune function of specific CTLs.
      METHODS: Fifteen patients with II to III stage positive HLA -A0201+ and NY-ESO-1+
      were enrolled in the Cancer Hospital Chinese Academy of Medical Sciences on the
      basis of preclinical experiments from November 2014 to October 2015, and their
      peripheral blood mononuclear cells (PBMCs) and peripheral blood lymphocytes
      (PBLs) were isolated. The PBMCs were induced into DCs and pulsed with NY-ESO-1
      peptide. The phenotypes of DCs were stained with antibodies against HLA
      DR+CD11c+,CD80+,CD83+ and CD86+, and subsequently analyzed by multichannel flow
      cytometry (FCM). The killing effects of CTLs pulsed with HLA-A0201-binding
      peptide NY-ESO-1 and the potential of autologous DCs pulsed with NY-ESO-1
      peptides in inducing specific cytotoxic T lymphocytes (CTLs) responses were
      determined. The patients were administered two infusions of auto-logous CTLs for
      1 time every two weeks. The total infusion was with 2 times. The immunological
      responses and clinical responses were examined in 1 week after the final
      administration. RESULTS: The immunophenotype of DCs pulsed with NY-ESO-1 peptide
      was analyzed, HLA-DR+CD11c+ cells (93.6%+/-1.2%), CD80+ cells (87.3%+/-3.6%),
      CD83+ cells (82.8%+/-2.5%) and CD86+ cells (93.4%+/-6.4%). PBLs isolated from
      patients primed by DCs pulsed with NY-ESO-1 peptide proliferated continuously and
      the proliferation index (PI) of the PBLs were analyzed. There was significant
      difference between the DCs loaded with polypeptides and those unloaded, though it
      could promote the proliferation of PBLs, but the PI was significantly lower than
      that of the DCs loaded with NY-ESO-1 peptide (P<0.05). The average percentage of
      special CTLs primed by DCs pulsed with NY-ESO-1 peptides was significantly higher
      than that in the control group (5.2%+/-1.2% vs. 0.4%+/-0.1%). CTLs induced by NY
      ESO-1 pulsed DCs exerted a stronger killing effect on T2 cell line pulsed with NY
      ESO-1 peptide than that in the control group at the ratio of E (effect) to T
      (target) as 30:1, P<0.05. The cytokine levels in the patients'sera such as IFN
      gamma, IL-2 and IL-12 were increased after treatments [(132.9+/-10.2) MUg/L vs.
      (46.4+/-3.1) MUg/L; (101.3+/-6.4) MUg/L vs. (26.7+/-1.2) MUg/L; (51.3+/-2.6)
      MUg/L vs. (26.4+/-1.1) MUg/L; all P<0.05], and the percentages of antigen
      specific CD8+IFN-gamma+ increased in these patients (P<0.01). CONCLUSION: Auto
      DCs pulsed with NY-ESO-1 peptides can induce the proliferation of allogenic CTLs,
      which elicit specific immune responses ex vivo or in vivo, and boost anticancer
      immunity markedly.

PMID- 29045967
TI  - [Early surgical treatment of multi-segmet intramedullary cervical spinal cord
      ependymoma].
AB  - OBJECTIVE: To investigate the early clinical treatment and prognosis of multi
      segment intramedullary cervical ependymoma. METHODS: Twenty patients with multi
      segment (more than 3 segments) intramedullary spinal ependymoma (McCormic grade
      I) were microsurgically treated with assistance of intraoperative
      neuroelectrophysiological monitoring. None of them received postoperative
      radiotherapy. Preoperatively all the patients underwent MRI examination and their
      neurologically function was assessed by McCormic classification method. They were
      followed up for an average of 2.7 years (The follow-up ranged from 3 months to 4
      years). All the patients underwent review of the MRI examination and their
      postoperative neurological function was assessed by McCormic classification
      method again. Evaluation was accomplished according to the results of the follow
      up. RESULTS: All tumors were intramedullary. The length of the tumor body varied
      from 3 to 8 vertebral segments with an average of 4.2 vertebral segments. Gross
      total removal was achieved in all the 20 patients through one-stage operation.
      The pathology of these patients was ependymoma (WHO grades I to II ). Two cases
      were lost during the follow-up due to the change of contact, but the hospital
      records of them showed that they recovered well at discharge. Eighteen cases were
      followed up constantly after operation. A case which ran through the whole
      cervical spinal cord had short-term mild motor dysfunction after operation, which
      manifested as weakness of the left side muscle strength to grade IV (which
      recovered to grade V during the follow-up period). Results of the follow-up
      showed that these 18 patients recovered well. Preoperative symptoms, such as limb
      numbness and painness were significantly alleviated. There was no obvious motor
      dysfunction. The bowel and bladder function of these 18 patients were almost
      normal. The McCormic scores of these 18 patients remained in grade I. No
      recurrence was found on review of the MRI examination. The main complications
      were a certain degree of deep sensory disturbance of lower extremities. The
      operation did not significantly affect the patient's life and work. CONCLUSION:
      Aggressive surgical therapy is a good treatment strategy for early multi-segment
      intramedullary cervical ependymoma. There is nearly no recurrence after operation
      and no postoperative radiotherapy is needed after gross total removal of tumors.

PMID- 29045968
TI  - [Comparative results of non-operative and operative treatment of humeral shaft
      fractures].
AB  - OBJECTIVE: To compare the difference between non-operative and operative
      treatment of humeral shaft fractures. METHODS: From March 2005 to October 2012,
      252 cases of humeral shaft fractures were treated and were adequately followed
      up. According to the treatment methods, the patients were divided into 2 groups:
      the non-operative group and the operative group. In the non-operative group,
      there were 76 cases treated with plaster/small splint fixation,meanwhile there
      were 176 cases treated with internal fixation either by plating or by nailing in
      the operative group. The follow-up parameters included: fracture healing rate,
      fracture union time, complications rate, Constant- Murley shoulder score and Mayo
      elbow score. RESULTS: The mean follow-up period was (31.24+/-20.06) months
      (ranging 6 to 103 months). There were no statistical differences in age, open
      fracture number, fracture site and Arbeitsgemeinschaft fur Osteosynthesefragen
      (AO) classification between the non-operative group and the operative group. The
      fracture healing rate: the non-operative group: 96.1%(72/76), the operative
      group: 97.7%(172/176), P=0.46; the fracture union time: the non-operative group:
      (10.24+/-2.93) weeks, the operative group: (10.69+/-2.51) weeks, P=0.22; the
      complication rate: the non-operative group: 5.3%(4/76),the operative group:
      15.3%(27/176), P=0.03. The complications included: nonunion: the non-operative
      group: 3.95%(3/76), the operative group: 2.3%(4/176), P=0.434; radial nerve
      palsies: the non-operative group: 0%(0/76), the operative group: 5.7%(10/176),
      P=0.035; bone split: the non-operative group: 0%(0/76), the operative group:
      1.7%(3/176), P=0.556; elbow stiffness: the non-operative group:1.3%(1/76), the
      operative group: 0.6%(1/176), P=1.000; shoulder pain: the non-operative
      group:0%(0/76), the operative group: 5.1%(9/176), P=0.061. The Constant-Murley
      shoulder score: the non-operative group: 97.37+/-4.94, the operative group:
      96.34+/-6.88, P=0.244. The Mayo elbow score: the non-operative group: 99.80+/
      1.72, the operative group: 99.49+/-2.73,P=0.923. CONCLUSION: The results of non
      operative treatment of humeral shaft fractures appeared with excellent results
      with lower complications rate compared with that of the operative treatment.

PMID- 29045969
TI  - [Clinical study on locking plate for the treatment of non-osteoporotic complex
      proximal humeral fractures].
AB  - OBJECTIVE: To describe long-term results of locking plate used for the treatment
      of non-osteoporotic fresh three- and four-part proximal humeral fractures with at
      least 2 years follow-up. METHODS: The functional outcomes and the complications
      of non-osteoporotic three- and four-part fresh proximal humeral fractures treated
      with locking plate were assessed retrospectively. The active range of motion, the
      Constant score, the University of California at Los Angeles (UCLA) shoulder
      score, the visual analogue score (VAS) were employed to evaluate the
      postoperative shoulder function, and the radiographic images were taken to
      evaluate the neck-shaft angle of the proximal humeral and postoperative implant
      related complications. RESULTS: From January 2007 to October 2014, 107
      consecutive fresh three- and four-part non-osteoporotic fresh proximal humeral
      fractures were treated with a locking plate in our department. Among them, 67
      patients completed at least 2 years follow-up. The average follow-up time was
      (43.9+/-23.3) months (range: 24-108 months). The mean Constant score was 87.1+/
      11.7 (range: 51-100), the mean UCLA score was 30.5+/-3.9 (range: 18-35), the mean
      VAS score was 1+/-2 (range: 0-7). The mean active forward flexion was 159.0
      degrees +/-19.3 degrees  (range: 80 degrees -180 degrees ), the mean external
      rotation was 36.8 degrees +/-19.5 degrees (0 degrees -80 degrees ) and the mean
      internal rotation was T11 level (T2-LS level). There were 11 patients who
      suffered from complications. Screw perforations were observed in 5 (7.5%)
      patients, avascular necrosis of the humeral head was observed in 9 (13.4%)
      patients and traumatic osteoarthritis was observed in 5 (7.5%) patients. Six
      patients showed two or more complications. There was no significant difference in
      outcomes when comparing the patients with three- part fractures (31 patients)
      with those with four-part fractures (36 patients). The rates of complications and
      avascular necrosis were significantly higher in the four-part fracture group than
      in the three-part fracture group. CONCLUSION: The locking plate is an effective
      method in treating three- and four-part non-osteoporotic fresh proximal humeral
      fractures. Strict surgical indication and precise surgical skill are the key
      points for successful treating non-osteoporotic fresh proximal humeral fractures.
      There is a higher rate of complications and avascular necrosis of the humeral
      head in the four-part fractures than in the three-part fractures.

PMID- 29045970
TI  - [Unilateral patellar resurfacing in bilateral total knee arthroplasty: a
      randomized controlled study].
AB  - OBJECTIVE: To perform unilateral patellar resurfacing and contralateral patellar
      retention in bilateral total knee arthroplasty (TKA) randomly, and to compare the
      clinical effects of patellar retention with patellar resurfacing in TKA. METHODS:
      In the study, 14 bilateral knee osteoarthritis (OA) patients were randomized in
      the bilateral TKA to receive unilateral patellar resurfacing and contralateral
      patellar retention, including 28 knees, all were females, 53 to 78 years old,
      with average (66.9+/-7.8) years, and the BMI was (26.3+/-1.8) kg/m2. All subjects
      were followed up from 3 to 12 months. The clinical effects were evaluated based
      on measurements of American Knee Society score (KSS), range of motion (ROM),
      anterior knee pain, patellar clunk, and patellar tilt angle (PTA). RESULTS: All
      the wounds healed primarily without significant complications, such as infection,
      aseptic loosening, patellar fracture and so on. The preoperative KSS scores of
      patellar resurfacing group were 38.9+/-22.2, and the scores changed to be 92.4+/
      6.7 after operation, which were added by 53.5+/-20.3. While in the patellar
      retention group, the KSS scores were 38.4 +/- 20.5 preoperatively, and after
      operation, which were added to be 92.1+/-4.2, and improved by 53.7+/-21.4. The
      differences in the changed KSS scores between TKA with and without patellar
      resurfacing were not statistically significant (Independent t-test, P=0.98). The
      ROM was changed from 95.4 degrees +/-13.5 degrees  preoperatively to 120.4
      degrees +/-8.9 degrees  postoperatively in the patellar resurfacing group and
      from 92.9 degrees +/-19.1 degrees  preoperatively to 120.4+/-8.4 degrees 
      postoperatively in the patellar retention group. The ROM of the two group were
      increased by 25.0 degrees +/-14.5 degrees  and 27.5 degrees +/-19.4 degrees 
      respectively. However, no remarkable differences were observed between the 2
      groups in the knee ROM (Independent t-test, P=0.70). At the end of the latest
      follow-up, 3 knees in the patellar resurfacing group and 2 knees in the patellar
      retention group had knee anterior pain, the incidences of anterior knee pain were
      21.4% and 14.3% respectively. There was no obvious difference for the incidence
      of post-operative anterior knee pain (Chi-square test, P=0.62). The incidences of
      post-operative patellar clunk in the 2 groups were all with 3 knees (21.4%),
      which had no significant difference in the 2 groups (Chi-square test, P=1.00).
      The post-operative PTA were 2.6 degrees +/-2.6 degrees  in the patellar
      resurfacing group and 3.6 degrees +/-2.9 degrees  in the patellar retention
      group, respectively. There was also no statistical difference between the 2
      groups (Chi-square test, P=0.36). CONCLUSION: For knee OA patients with mild or
      moderate patellar cartilage damage, performing patellar resurfacing or not didn't
      significantly affect anterior knee pain, patellar clunk, functional outcomes or
      patellar tracking after TKA. So we suggest retain patella in TKA for OA patients
      with mild or moderate patellar cartilage damage.

PMID- 29045971
TI  - [Technical improvement in retroperitoneal laparoscopic living donor nephrectomy:
      report of 193 cases].
AB  - OBJECTIVE: To summarize our experience of retroperitoneal laparoscopic living
      donor nephrectomy, our continuous technical improvements and refinement of this
      skill and standardization of each procedure of this operation. METHODS: Having
      approved by hospital ethical committee and local government administration, a
      total of 193 living donors underwent retroperitoneal laparoscopic living donor
      nephrectomy from Dec.2003 to Feb. 2016 in our department. Under general
      anaesthesia, the operation was performed through 3 lumbar ports. After the kidney
      was liberated fully and the ureter was severed 7-8 cm under the lower pole of the
      kidney, the renal artery and vein were blocked with endo-cut or hem-o-lok
      separately and then severed. Then the kidney was taken out quickly and flushed
      with 4  degrees C kidney preserving fluid immediately, the donor kidneys were
      then preserved in iced saline until kidney transplantation. Clinical data about
      operation time, volume of blood loss, perioperative complications, renal function
      of both donors and recipients before and after operation were collected. RESULTS:
      The 193 retroperitoneal laparoscopic living donor nephrectomy operations were
      successful with only one operation was converted to open living donor nephrectomy
      because of hemorrhage and unclear operation field during the operation. The
      average operation time was 85 min (55-135 min), the average blood loss was 60 mL
      (20-200 mL), and no donor needed blood transfusion during or after operation.
      Three donors were found to have hematoma of renal fossa after operation and none
      of them required further treatment. The average hospital stay after operation was
      5.7 days (4-9 days). In the study, 162 donors were followed up for an average of
      42 months (1-58 months) and they were all healthy. Two kidney recipients had
      urinary bladder anastomosis leakage after operation and both needed surgical
      repair, a new anastomosis of ureter and bladder were made. Three kidney
      recipients had kidney subcapsular hematoma but required no further treatment. One
      kidney recipient had delayed graft function and recovered finally and the renal
      function of other recipients were all normal. Renal function of both donors and
      recipients during the follow up period were normal. CONCLUSION: Retroperitoneal
      laparoscopic living donor nephrectomy is a safe and reliable technique, it may
      become a standardized operation for living kidney transplantation after
      continuous technical improvement. Precautions must be taken to avoid
      complications and a skilled hand is necessary for success.

PMID- 29045972
TI  - [Acetylsalicylic acid treatment enhanced immunomodulatory function of mesenchymal
      stem cells derived from gingiva].
AB  - OBJECTIVE: To analyze the role of acetylsalicylic acid (ASA) in immunomodulation
      of mesenchymal stem cells derived from gingiva (GMSCs), and to explore the role
      of ASA in enhancing the immumomodulation of GMSCs and the capacity of GMSCs to
      treat immune disorders and the underlying mechanism. METHODS: Flow cytometry
      analysis were used to analyze the role of ASA in the expression of stem cells
      surface markers CD146, CD105, CD90, CD34 and CD45 in GMSCs,and the GMSCs
      proliferation was analyzed by 5-bromo-2-deoxyuridine (BrdU) staining and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The GMSCs and
      T cells co-culture system was established to analyze the role of ASA in
      immunomodulation of GMSCs by measuring T cell apoptosis using flow cytometry
      analysis and inflammatory cytokines using enzyme linked immunosorbent assay
      (ELISA). Further more, the dextran sulfate sodium (DSS) induced colitis mouse
      model was established and the mouse body weight, disease activity score,
      histological index and pathological change of colons were analyzed after GMSC
      infusion. RESULTS: The proliferation of GMSCs and the expressions of CD105, CD146
      in GMSCs were increased after ASA treatment. In the GMSCs and T cells co-culture
      system, GMSCs induced T cells apoptosis and inhibited interferon gamma (IFN
      gamma) and tumor necrosis factor alpha (TNF-alpha) secretion by T cells, which
      were enhanced by ASA treatment. In vivo, GMSCs infusion could ameliorate DSS
      induced colitis, including inhibited DSS-induced mouse body weight loss,
      decreased disease activity score and histological index, and decreased
      inflammation cells infiltration in colons, as shown by hematoxylin-eosin (HE)
      staining. Moreover, the therapeutic effects of GMSC infusion on DSS-induced
      colitis could be enhanced by ASA treatment. Mechanically, ASA treatment increased
      FasL expression of Fas/FasL death pathway in GMSCs to induce T cells apoptosis.
      CONCLUSION: ASA enhanced immunomodulation of GMSCs and increased the capacity of
      GMSCs to ameliorate DSS-induced colitis in mice.

PMID- 29045973
TI  - [Application of three-dimensional reconstruction of the enhanced CT with iPlan
      CMF software in head and neck neoplasms].
AB  - OBJECTIVE: Three-dimensional reconstruction of the enhanced CT is increasingly
      becoming a valuable tool in head and neck neoplasms. The aim of this study is to
      reconstruct three-dimensional imaging of tumor and its surrounding important
      anatomical structure using iPlan CMF software, and to investigate the application
      of three-dimensional tumor mapping technique for the diagnosis and treatment of
      the head and neck neoplasms. METHODS: In the study, 13 cases with head and neck
      tumors in Department of Oral and Maxilloficial Surgery, Peking University School
      and Hospital of Stomatology from June 2014 to June 2015 were studied using spiral
      CT scanning technology based on the same scanning condition. iPlan CMF software
      was used to read the original CT data, and surface shaded technology was applied
      to reconstruct the spatial relationship of the tumor, vessel and skull. The
      distance between the tumor and its surrounding important anatomical structure
      could be measured. iPlan CMF software was also used to accomplish the virtual
      osteotomy to expose the tumor, vessel and skull. The preoperative preparation,
      operative situation and postoperative complication were reviewed. RESULTS: In
      this study 6 patients were male and 7 female. The age range was from 23 to 65
      years, and the median patient age was 50 years. The three-dimensional
      reconstruction image clearly demonstrated the extent of the tumor size, location,
      and the relation to its surrounding important anatomical structure. According to
      the three-dimensional image, the surgical risk of the patients was evaluated. The
      preoperative preparation and surgeries were successfully performed for 10
      patients. Blood transfusion for 3 patients was considered before the surgery and
      actually accomplished during the operation. The operations for 2 patients were
      performed with the help of doctors from other departments. Only one patient had
      hoarseness because the tumor resulted from the pneumogastric nerves. For 10
      patients, the average operation time was (202+/-135) min, and the average
      operation bleeding was (235+/-252) mL. The other 3 patients were not suitable
      cases for surgery. CONCLUSION: The three-dimensional reconstruction of enhanced
      CT image with iPlan CMF software is very helpful to make the treatment plan to
      avoid damaging important anatomical structures and postoperative complications.

PMID- 29045974
TI  - [Echocardiographic diagnosis of infracardiac total anomalous pulmonary venous
      connection].
AB  - OBJECTIVE: To investigate the clinical usefulness of echocardiography in the
      diagnosis of infracardiac total anomalous pulmonary venous connection (ITAPVC) in
      neonates and infants. METHODS: Retrospective analysis on 8 patients with ITAPVC
      was performed using echocardiography between April 2006 and December 2016. There
      were 4 boys and 4 girls with a mean age of 79.8 days (ranging from 15 to 195
      days). A combined scanning via parasternal, subcostal and apical acoustic windows
      had been employed to diagnose ITAPVC and to trace the course and site of the
      anomalous pulmonary venous drainage, and to confirm the direction of the inter
      atrial shunt and enlargement of right atrium and right ventricle. RESULTS: Of the
      8 patients who received echocardiography, ITAPVC was diagnosed in 7 patients. Mis
      diagnosis by echocardiography was encountered in one patient. The diagnosis by
      echocardiography was compatible with the operative findings in 5 patients
      receiving surgery and with the results of multislice computed tomography in 6
      patients. The diagnostic accuracy rate of ITAPVC was 87.5%. The indirect signs
      obtained from echocardiogram was coexistence of a small malformed, triangle
      shaped left atrium and right to left shunting at atrial level with dilatation and
      tortuousness of portal vein or hepatic vein and abundant blood flow in liver. The
      direct signs was total pulmonary veins unconnected with left atrium, whose
      confluence joining into vertical vein drained right-inferiorly to portal vein or
      hepatic vein through diaphragm. Three parallel vessels including vertical vein,
      abdominal aorta and inferior vena cava arranged anteriorly, left-posteriorly and
      right-posteriorly with the opposite flow directions of inferior vena cava and the
      other two were found on sub-costal view. Sites of the drainage to the infra
      diaphragm veins located portal vein in 8 patients. Stenosis of site of vertical
      vein connecting to portal vein or hepatic veins occurred in 3 patients.
      CONCLUSION: Echocardiography has significant value in the diagnosis of pediatric
      ITAPVC and is capable of providing important structural and hemodynamic
      information for preoperative assessment of surgery. With multiple windows and
      multiple sections, ITAPVC could be diagnosed accurately by echocardiography.
      However, it is necessary to differentiate ITAPVC with intrahepatic portosystemic
      venous shunts or hepatic arteriovenous fistula.

PMID- 29045976
TI  - [Anatomy and histology characteristics of lymph node in nude mice].
AB  - OBJECTIVE: To compare the differences of anatomical and histological
      characteristics of lymph nodes between BALB/c nude mice and BALB/c mice. METHODS:
      Firstly, twenty BALB/c nude mice and twenty BALB/c mice were dissected by using a
      surgical microscope. Secondly, the differences of T cells and B cells at the
      lymph node were compared by the expressions of CD3 and CD20 immunohistochemistry
      dyes. RESULTS: There were, on average, 23 nodes per mouse contained within the
      large lymph node assembly in the BALB/c nude mouse. The anatomical features of
      the lymph node distribution in the nude mice were mainly found in the neck with
      relatively higher density. There were two lymph nodes both in the submandible
      lymph nodes group and in the superficial cervical lymph nodes group (the
      constituent ratios were 95% and 90%, respectively) in the BALB/c nude mice, but
      there were four lymph nodes (the constituent ratios were 95% and 90%,
      respectively) in the BALB/c mice. There were significant difference between the
      BALB/c nude mice and the BALB/c mice. Mostly there were two lymph nodes of deep
      cervical lymph nodes both in the BALB/c nude mice and the BALB/c mice (the
      constituent ratios were 95% and 100%, respectively). There were no significant
      difference between the BALB/c nude mice and the BALB/c mice. We confirmed that
      the number of CD3-positive T lymphocytes in lymph nodes of the nude mice
      decreased greatly as compared with the BALB/c mice. Expressions of CD3 in T cells
      were 95% and 100% in the BALB/c nude mice and in the BALB/c mice, respectively.
      There were significant differences between the BALB/c nude mice and the BALB/c
      mice. Expressions of CD20 in B cells were 95% and 100% in the BALB/c nude mice
      and in the BALB/c mice, respectively. There was no significant difference between
      the BALB/c nude mice and BALB/c mice. CONCLUSION: The anatomical pictures of
      lymph node distribution in the nude mouse will be benefit to those who are
      interested. The anatomical features of the lymph node local higher density in
      neck of the nude mouse and lack of CD3-positive T lymphocytes would be useful for
      obtaining a better understanding of localized lymph node metastasis of oral
      transplant tumors.

PMID- 29045975
TI  - [Comparison and discussion of different surgical methods used to treat
      vesicovaginal fistulas].
AB  - OBJECTIVE: To compare the feasibility and prognosis of different surgical methods
      used for vesicovaginal fistulas and to explore the value of electrocoagulation
      treating small ones. METHODS: The medical data of 19 patients who had undertaken
      transvaginal VVF repairs in Peking University People's Hospital between October
      2008 and November 2016 were retrospectively collected. The follow-ups were
      performed. The patients' age ranged from 31 to 55 years with the median age of 48
      years and the history length ranged from 1 month to 24 months with the median
      length of 3 months. Their fistula situation, surgical methods and prognosis were
      analyzed and the differences and similarities were compared. RESULTS: Three
      patients (15.79%) was performed by electrocoagulation, 4 (21.05%) by transvaginal
      repair, 5 (21.32%) by laparoscopic repair and 7(36.84%) by open operation. Except
      one patient who rejected urinary catheter and D-J catheters, the rest of the
      patients discharged with catheters. Twelve patients (63.2%) got full satisfaction
      with one operation. One of the 3 patients who undertook electrocoagulation
      repeated the operation for twice and got completely cured within 1 month while
      the other two undertook the operation once and got dry within 1 month. Three
      patients who undertook transvaginal repair got dry within 1 month. Two of the 5
      patients who undertook laparoscopic repair had readmission for a second operation
      and the other 3 got dry after operation. Five of the 7 open repair patients got
      dry while the other 2 attempted other center for treatment. CONCLUSION:
      Transvaginal repair has been the main surgery procedure for VVF, but it is
      limited by the location of fistula and the condition of vaginal. For patients not
      suitable for transvaginal repair, laparoscopic repair and open surgery are
      feasible. However both laparoscopic repair and open surgery are more invasive.
      Based on that, electrocoagulation becomes a better choice. In our research,
      patients with small and high location fistula treated by electrocoagulation got a
      higher cure rate and bear less surgical trauma. Electrocoagulation used in the
      treatment of VVF showed advantages of less trauma, less bleeding and better
      satisfaction. Fistulas with low location were more suitable for transvaginal
      repair. Complex VVF, especially with narrow ureteral open and ureteral fistulas,
      were more suitable for open and laparoscopic repair. As for single and small
      fistula, the electrocoagulation can be the first choice.

PMID- 29045977
TI  - [Clinical and genetic characteristics of Williams-Beuren syndrome: 2 cases
      report].
AB  - To explore the clinical and genetic characteristics of Williams-Beuren syndrome
      (WBS) and to raise awareness of the disease. The characteristics of clinical
      manifestations, personal history, cardiac ultrasound, brain magnetic resonance
      imaging (MRI), electroencephalogram (EEG) and chromosome detection results of two
      cases with WBS were analyzed. The two patients were both male and the age was 11
      months and 1 day, and 9 months and 9 days, respectively. They both suffered from
      cardiovascular malformation: case one presented supravalvular aortic stenosis,
      and case two showed atrial septal defect and patent ductus arteriosus. Both of
      the cases were exhibited characteristic facial features of WBS, including full
      orbital, spherical nose, flat nasal bridge, long philtrum and thick lips. For the
      mental development, case one displayed moderate to severe developmental
      retardation, and case two showed severe developmental retardation. In addition,
      case one presented bilateral indirect inguinal hernia and hydrocele, and case two
      manifested feeding difficulties, buried penis and infantile spasms. Personal
      history: case one's mother had tocolytic therapy during pregnancy period, and
      case one was born at full-term by cesarean section due to amniotic fluid
      pollution. Supplementary examination: brain MRI of the two cases were no
      significant abnormalities; the EEG of case two showed hypsarrhythmia, and the
      epileptic spasms were recorded. Chromosome detection results: case one was
      identified as 7q11.23 deletion including the fragment deletion mutation of
      elastin (ELN) gene by multiplex ligation dependent probe amplification method,
      and case two was found with 7q11.21q11.23 deletion by high resolution G-band
      method. The two cases with WBS both had cardiovascular malformations, special
      facial features, mental retardation and connective tissue or urinary system
      abnormality. The supravalvular aortic stenosis of case one may be associated with
      the deletion of ELN gene, and the occurrence of epilepsy of case two may be
      related to the q11.21 deletion beyond the 7q11.23 region.

PMID- 29045978
TI  - [Clinicopathologic features of infant dysembryoplastic neuroepithelial tumor: a
      case report and literature review].
AB  - Dysembryoplastic neuroepithelial tumor (DNT) has traditionally been viewed as
      rare benign tumors that present with seizure widely considered curable with
      surgery alone. Most DNTs occur in childhood and young adults. However, rare
      reported cases occur in infants. This paper reported an infant case of DNT and
      its diagnosis, differential diagnosis, treatment, molecular features and
      prognosis based on the review of current literatures. The age onset of this
      patient was only 11 months old. The clinical manifestations were partial seizures
      and the imaging data untypical; CT and MRI were all supportive of astrocytoma.
      Typical glioneuronal element histologic features could be seen, which contained
      oligodendrocyte-like cells attached to bundles of axons and neurons floating in a
      myxoid interstitial fluid. Meanwhile, some atypical regions could also be seen.
      These atypical regions showed a mixture of oligodendrocyte-like cells and neurons
      without a myxoid interstitial fluid, which were easily misdiagnosed. The
      BRAFV600E mutation was not detected. This patient had a good response to drug
      therapy. Totally surgical resection of the tumor was conducted. The patient had
      been seizures free for 6 months. In conclusion, DNT is a rare and well prognostic
      tumor (WHO grade I), which most often arise in children in the setting of
      medically refractory epilepsy. The most common tumor location was temporal.
      Because clinical symptoms, imaging and histological features of DNT and other low
      grade gliomas broadly overlap such as ganglioglioma, pilocytic astrocytomas and
      oligodendroglioma et al., differential diagnosis should be made carefully. The
      glioneuronal element was the histopathological hallmark of DNT. In addition, some
      untypical regions should also be called attention. Although BRAFV600E mutation
      didn't exist in this case, it played a role in differential diagnosis because it
      has been previously recorded that BRAFV600E mutation was a common feature of DNT.
      Infant patients have their own characteristics. For example, drug therapy worked
      well and the imaging data was untypical. Doctors should improve the understanding
      of this disease to avoid unnecessary radiotherapy or chemotherapy.

PMID- 29045979
TI  - [Changes of serum Krebs von den Lungen-6 levels in interstitial lung disease
      associated with dermatomyositis and secondary Sjogren's syndrome: a case report].
AB  - Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders
      characterized by various patterns of inflammation and fibrosis in the
      interstitium of the lung. The underlying pathogenesis of ILDs is complex and
      associated with multiple rheumatologic conditions, such as systemic sclerosis,
      rheumatoid arthritis, pollymyositis and dermatomyositis, Sjogren's syndrome, and
      systemic lupus erythematosus. As the disease progresses, excessive pulmonary
      fibrosis impairs alveolar gas exchange and damages pulmonary function. The common
      methods to diagnose ILDs, such as clinical manifestations, pulmonary function
      test, and radiological examinations are not specific for ILDs and not able to
      diagnose ILDs at the early stage due to their low sensitivity. So, the easy way
      is important to diagnose ILDs. One important biomarker for ILDs is the high
      molecular-weight glycoprotein, Krebs von den Lungen-6(KL-6). KL-6 encoded by the
      MUC1 gene is a mucin-like glycoprotein with high molecular weight and expressed
      predominantly on the cell surface of type II alveolar epithelial cells, and is
      detectable in the serum of patients with ILDs. We here report a case of ILDs
      associated with dermatomyositis and secondary Sjogren's syndrome. A 60-year-old
      woman was admitted to our hospital with the chief complaints of debilitation, dry
      mouth, dyspnea and astasia. ILDs associated with dermatomyositis and secondary
      Sjogren's syndrome was diagnosed clinically when the following criteria were
      satisfied: (1) development of dyspnea within 2 months of presentation, (2)
      pulmonary dispersion dysfunction, (3) bilateral infiltrative shadows on chest
      high resolution computed tomography (HRCT). She was treated with prednisone 50
      mg/d prior to admission, but the result of therapy was not good. In our hospital
      she was treated with intravenous methylprednisolone and cyclophosphamide and oral
      hydroxychloroquine sulfate. Subsequently, her serum KL-6 levels gradually
      decreased after treatment, pulmonary diffuse function improved, and the
      improvement in the clinical manifestation and HRCT findings were observed.
      Nevertheless, the combination treatment of glucocorticoid and cyclophosphamide
      had contributed to the favourable outcomes. In conclusion, detection of serum KL
      6 levels in ILDs associated with connective tissue diseases may be beneficial to
      making a definitive diagnosis, predicting the prognosis and monitoring the
      disease activity, which would be of great help in clinical practice. However, a
      well-designed clinical study with more patients and a longer follow-up period are
      required to arrive at a more conclusive judgment on the role of serum KL-6 in
      patients with ILDs.

PMID- 29045980
TI  - [Anti-neutrophil cytoplasmic antibodies-associated vasculitis with lung
      hemorrhage in the patient on maintenance haemodialysis: a case report].
AB  - Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is
      usually a multisystem disorder, and pulmonary renal syndrome is a common
      presentation. Patients with AAV are less likely to experience relapse when they
      progress to end-stage renal disease (ESRD). We report a rare case of diffuse
      alveolar hemorrhage (DAH) in relapsing AAV after eight years of haemodialysis. A
      58-year-old woman was admitted to our hospital with the chief complaints of
      dyspnea and hemoptysis accompanied by anemia, fever, fatigue, and weight loss.
      She had elevated anti-myeloperoxidase (MPO) titer. The computer tomoghraphy
      showed diffuse alveolar hemorrhage. After the recurrent episode of AAV was
      diagnosed, she underwent the following therapy: Plasmapheresis was initiated
      within 24 h after admission, 3 000 mL of plasma was removed per session, and the
      anticoagulation of citrate was applied during plasmapheresis. Five plasmapheresis
      treatments were performed, and after three apheresis sessions, the pulmonary
      hemorrhage ceased. Other treatments included a methylprednisolone bolus, tapered
      to oral prednisone and cyclophosphamide. Regular hemodialysis was scheduled.
      These treatments resulted in resolution of the inflammatory symptoms, DAH
      improved. Her anti-MPO level decreased. The patient was discharged in good
      condition. AAV with DAH is usually acute at the onset and is generally a
      condition with high morbidity and substantial mortality. Therefore, prompt
      diagnosis and aggressive treatment are needed to improve survival.

PMID- 29045981
TI  - Renal Ewing's sarcoma/primitive neuroectodermal tumor: a case report and
      literature review.
AB  - Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) in the kidney is a
      rare but high-grade malignant tumor that affects predominantly elder children and
      adolescents. Patients mostly present with nonspecific symptoms such as abdominal
      pain and gross hematuria. Since EWS/PNET has a rapid clinical progression with
      early metastasis and death, it is essential to make an accurate and early
      diagnosis. Once diagnosed, multimodality treatment, including radical surgery
      combined with adjuvant chemotherapy, and radiotherapy if necessary, is
      recommended. Unfortunately, there are no characteristic signsthat have been
      described in ultrasonography or any other imaging modalities so far. The
      diagnosis of EWS/PNET is now based on a classical histological and
      immunohistochemical investigation complemented by a demonstration of specific
      chromosomal changes. Strong immunoreactivity to CD99 is ubiquitous, and t(11;22)
      translocation is seen in approximately 90% of EWS/PNET. Herein, we report a
      patient with such condition. The patient was a young woman, and she presented
      with sudden right flank pain clinically. Ultrasonography revealed a large
      heterogeneous mass in the lower pole of her right kidney. The tumor compressed
      the renal pelvis and led to upper pole caliectasis. Color Doppler demonstrated
      blood flow with a pulsatile arterialized waveform within the mass. The patient
      received radical nephrectomy with right renal vein and vena cava thrombectomy. A
      search for other sites of tumor involvement yielded negative results. And six
      cycles of chemotherapy were sequentially performed. The diagnosis of EWS/PNET was
      confirmed based on primitive small round cell histology and characteristic
      immunohistochemical results. She was still alive with no evidence of recurrence
      five years after initial diagnosis. We would like to point out that ultrasound is
      still a useful method for initial assessment, and ultrasound-guided fine needle
      aspiration may play an important role in determining preoperative diagnosis.

PMID- 29045982
TI  - Stuck in the Office.

PMID- 29045983
TI  - Effects of a Brief Psychosocial Intervention on Inpatient Satisfaction: A
      Randomized Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: Increasing attention is being paid to patients'
      experience of hospitalization. BATHE (a brief psychosocial intervention that
      addresses Background, Affect, Trouble, Handling, and Empathy) has been found to
      improve patients' outpatient experiences but has not yet been studied in
      inpatient settings. This randomized controlled trial (RCT) examined whether daily
      administration of BATHE would improve patients' satisfaction with their hospital
      experience. METHODS: BATHE is a brief psychosocial intervention designed to
      reduce distress and strengthen the physician-patient relationship. In February
      through March 2015 and February through March 2016, 25 patients admitted to the
      University of Virginia Family Medicine inpatient service were randomized to usual
      care or to the BATHE intervention. Participants completed a baseline measure of
      satisfaction at enrollment. Those in the intervention group received the BATHE
      intervention daily for five days or until discharge. At completion, participants
      completed a patient satisfaction measure. RESULTS: Daily administration of BATHE
      had strong effects on patients' likelihood of endorsing their medical care as
      "excellent." BATHE did not improve satisfaction by making patients feel more
      respected, informed or attended to. Rather, effects on satisfaction were mediated
      by patients' perception that their physician showed "a genuine interest in me as
      a person." CONCLUSIONS: Our study suggests that patients are more satisfied with
      their hospitalization experience when physicians take a daily moment to check in
      with the patient "as a person" and not just as a medical patient. The brevity of
      the BATHE intervention indicates that this check-in need not be lengthy or overly
      burdensome for the already busy inpatient physician.

PMID- 29045984
TI  - Results of the 2017 National Resident Matching Program(r) and the American
      Osteopathic Association Intern/Resident Registration Program.
AB  - BACKGROUND AND OBJECTIVES: The purpose of medicine as a profession is to meet the
      health needs of people and communities. Despite empirical evidence worldwide that
      an appropriate foundation of primary care in a health care system leads to
      improved health outcomes, improved experience of health care, a reduction in
      health disparities, and lower overall cost of care, publicly available data from
      National Resident Matching Program(r) (NRMP) and the American Osteopathic
      Association (AOA) Intern/Resident Registration Program show that PGY-1 family
      medicine and primary care positions offered in the NRMP Match continue to grow,
      but are losing ground in comparison to the growth of non-primary care
      specialties. In ACGME-accredited family medicine programs, DO students have been
      displacing non-US citizen IMGs while the proportion of US seniors has remained
      stable over the past decade. The impact of the displacement of non-US citizen
      IMGs by DO students in ACGME programs is unknown and deserves future research.
      Continuing trends in the growth of non-primary care specialties should raise
      great concern that the current primary shortage will be exacerbated, not serving
      the needs of the population. A major overhaul of the graduate medical education
      (GME) system is required to align the medical education system with the
      transformation of the health care system needed to improve quality, population
      health, and cost control.

PMID- 29045985
TI  - Entry of Medical School Graduates Into Family Medicine Residencies: 2016-2017.
AB  - BACKGROUND AND OBJECTIVES: This annual report is an expansion on previous reports
      in this series that provides further evidence that the current medical school
      system is failing, collectively, to produce the primary care workforce that is
      needed to achieve optimal health in the United States. Inclusion of data on the
      performance of DO-granting and international medical schools, creates a more
      complete and complex picture of the contribution of all medical school types to
      the primary care workforce that should allow stakeholders to set goals, identify
      institutions with models from which to learn, and develop strategies for
      continuous improvement. US MD graduates made up 49% of the entering first-year
      class of family medicine residencies accredited by the Accreditation Council for
      Graduate Medical Education (ACGME), a percentage that is not statistically
      changed from the 11-year average of 46%. Over the same time, the percentage of DO
      graduates in the entering class has been increasing at an annual rate of 1%,
      while the percentage of international graduates has been decreasing in a
      reciprocal manner. Production of family medicine graduates has varied widely
      between and within medical school types. The number of graduates entering family
      medicine programs accredited by the ACGME underrepresents the overall family
      medicine output by US medical schools since up to a third of DO graduates have
      historically entered residencies accredited only by the American Osteopathic
      Association. While marked differences between public and private continue among
      US MD-granting medical schools, the percentages are nearly equal between public
      and private for DO-granting medical schools, with a slightly higher percentage
      for private schools.

PMID- 29045986
TI  - Impact of Residency Training Redesign on Residents' Clinical Knowledge.
AB  - BACKGROUND AND OBJECTIVES: The In-training Examination (ITE) is a frequently used
      method to evaluate family medicine residents' clinical knowledge. We compared
      family medicine ITE scores among residents who trained in the 14 programs that
      participated in the Preparing the Personal Physician for Practice (P4) Project to
      national averages over time, and according to educational innovations. METHODS:
      The ITE scores of 802 consenting P4 residents who trained in 2007 through 2011
      were obtained from the American Board of Family Medicine. The primary analysis
      involved comparing scores within each academic year (2007 through 2011),
      according to program year (PGY) for P4 residents to all residents nationally. A
      secondary analysis compared ITE scores among residents in programs that
      experimented with length of training and compared scores among residents in
      programs that offered individualized education options with those that did not.
      RESULTS: Release of ITE scores was consented to by 95.5% of residents for this
      study. Scores of P4 residents were higher compared to national scores in each
      year. For example, in 2011, the mean P4 score for PGY1 was 401.2, compared to the
      national average of 386. For PGY2, the mean P4 score was 443.1, compared to the
      national average of 427, and for PGY3, the mean P4 score was 477.0, compared to
      the national PGY3 score of 456. Scores of residents in programs that experimented
      with length of training were similar to those in programs that did not. Scores
      were also similar between residents in programs with and without individualized
      education options. CONCLUSIONS: Family medicine residency programs undergoing
      substantial educational changes, including experiments in length of training and
      individualized education, did not appear to experience a negative effect on
      resident's clinical knowledge, as measured by ITE scores. Further research is
      needed to study the effect of a wide range of residency training innovations on
      ITE scores over time.

PMID- 29045987
TI  - Perspectives of Family Medicine Clerkship Directors Regarding Forward Feeding: A
      CERA Study.
AB  - BACKGROUND AND OBJECTIVES: Forward feeding signifies sharing information about
      learners for purposes of professional and academic advancement, and promotes
      progression toward a competency-based educational continuum. The aim of this
      study is to assess reasons for difficulty or failure of the family medicine
      clerkship and investigate utilization and methods of forward feeding. Reasons
      behind medical school policies regarding forward feeding are also evaluated.
      METHODS: Data were collected through the 2013 Council of Academic Family Medicine
      (CAFM) Educational Research Alliance (CERA) Family Medicine Clerkship Director
      survey. Directors rated reasons for clerkship difficulty or failure on a 6-point
      Likert scale. They also reported if they utilized forward feeding, to whom, and
      the communication method used. Finally, they were asked about factors influencing
      institutional policy toward forward feeding, including threats of litigation.
      RESULTS were compared between public and private schools, and based on tenure as
      clerkship director. Analyses were performed using chi-square or Fisher's exact
      test. RESULTS: Knowledge deficits were the most common reason for clerkship
      difficulty and failure, followed by professionalism difficulties. Over half of
      respondents engage in forward feeding, and almost all pass this information to
      other clerkship directors. Concern for student privacy and faculty bias were
      noted as two important factors influencing school policy. While almost half of
      respondents felt that litigation fears influenced their school's approach to
      forward feeding, few were aware of any related litigation. CONCLUSIONS: Forward
      feeding is only utilized by half of clerkship directors. More studies regarding
      the potential impacts of this practice are warranted.

PMID- 29045988
TI  - Postgraduate Experiences With an Advanced Reproductive Health and Abortion
      Training and Leadership Program.
AB  - BACKGROUND AND OBJECTIVES: Family physicians are critical to reproductive health
      service provision including miscarriage management and abortion care, but many
      graduates report barriers in integrating these services into practice. We
      designed and implemented CREATE (Continuing Reproductive Education for Advanced
      Training Efficacy), an elective advanced training and leadership program for
      senior residents aimed to help new graduates integrate miscarriage and abortion
      care into practice. METHODS: We surveyed all 53 program graduates at graduation,
      and 47 completed a follow-up survey in March 2016. We describe program graduates'
      current reproductive health practices and differences by respondent
      characteristics. We report facilitators (or enabling factors) and barriers that
      graduates encountered in attempting to integrate reproductive health care into
      practice, as well as the perceived impact of the CREATE program. RESULTS: Forty
      two percent of CREATE graduates were providing miscarriage management and 35%
      were providing abortion care at the time of the follow-up survey. Factors
      associated with abortion provision at follow-up include strength of intention to
      provide at graduation and higher volume of uterine aspirations performed during
      residency. Graduates reported a range of barriers, including internal factors
      such as strength of competing interests, and external barriers such as
      administrative and staff resistance. Graduates found the additional procedural
      training, networking opportunities, and the complication simulation to be the
      most helpful aspects of the CREATE program. CONCLUSIONS: The CREATE program model
      may provide a useful template for family medicine residencies working to
      incorporate advanced abortion training or other advanced procedural skills into
      their curricula. Future curricular interventions should consider providing
      additional postgraduate support, particularly in provider shortage areas.

PMID- 29045989
TI  - Human Papillomavirus Vaccination Training Experience Among Family Medicine
      Residents and Faculty.
AB  - BACKGROUND AND OBJECTIVES: Residency training is a pivotal time to establish
      skills for career-long practices, particularly for challenging skills such as
      human papillomavirus (HPV) vaccine recommendation. Training experience and
      preferences related to delivering HPV vaccine recommendations were examined for
      family medicine (FM) residents and faculty. METHODS: Residents (n=28) and faculty
      (n=19) were identified through a national FM residency directory and recruited
      from training programs in Florida. Participants completed a phone interview
      assessing key aspects of HPV vaccine recommendation training. Interviews were
      audio recorded, transcribed verbatim, and analyzed using content analysis. A
      brief follow-up survey assessing training, practices, and demographics was
      emailed after the interview. RESULTS: Residents' training experience with HPV
      vaccine recommendation varied from none to extensive, and was often self
      directed. Variation in training was seen between and within programs. Faculty
      often noted HPV vaccination training was not standardized and residents lacked
      instruction about effective communication. Most programs relied on preceptors for
      training residents but training from preceptors varied widely and was often not
      standardized within the program. CONCLUSIONS: This study identified a lack of
      consistent and standardized training for delivering HPV vaccine recommendations.
      A training curriculum that uses multiple modalities and reflects resident and
      faculty preferences is needed.

PMID- 29045990
TI  - Electronic Health Record Impacts on Family Medicine Teachers: Survey of Third
      Year Medical Student Clerkship Preceptors at an Academic Medical Center.
AB  - BACKGROUND AND OBJECTIVES: Electronic Health Record (EHR) use in clinical
      practice has accelerated in recent years. While several aspects of EHR use have
      been extensively studied, there is little data on EHR impacts on medical student
      educators, especially those involved in outpatient family medicine. This study
      evaluated perceived impacts of EHR use on clinician teachers of outpatient family
      medicine. METHODS: The study used a mixed methods survey of clinicians who teach
      third-year medical students during the required family and community medicine
      outpatient clerkship at a Mid-Atlantic medical school. RESULTS: Among 50
      completed surveys, most respondents reported that the EHR had impacted their
      teaching (70% reported at least one negative effect; 84% reported at least one
      positive effect). Positive impacts included more easily viewing information, more
      effectively teaching evidence-based medicine, and teaching about EHR use itself.
      Negative impacts included less time teaching or interacting with students, and a
      perception that EHR use impedes development of students' critical thinking and
      clinical integration skills. Providers who have taught medical students both with
      and without EHR in place (>P=.024), those over 50 years old (>P=.019), and those
      with at least 5 years teaching experience (>P=.006) were more likely to report
      negative impacts. CONCLUSIONS: Most preceptors reported that EHR use had both
      positive and negative impacts on their teaching of medical students, though the
      negative effects were perceived by respondents as more substantial, consistent
      with a theme of decreased enthusiasm for teaching due to EHR use. These findings
      can be used to help inform faculty development and education initiatives.

PMID- 29045991
TI  - Naloxone Counseling for Harm Reduction and Patient Engagement.
AB  - BACKGROUND AND OBJECTIVES: The United States is experiencing an epidemic of
      opioid-related deaths. Naloxone, the drug of choice for reversing acute opioid
      overdose, is not routinely prescribed for outpatient use. The aims of this
      project were to improve naloxone awareness, increase naloxone prescribing, and
      prevent opioid overdoses. METHODS: A naloxone counseling intervention was
      implemented in three family health centers by an interprofessional team of
      providers including family medicine physicians, clinical pharmacists, and social
      workers. An outreach letter was designed with provider input, an electronic order
      set was developed to facilitate prescribing, and intranasal naloxone kits were
      assembled for free dispensing. Providers and staff received education about
      opioid overdose and naloxone prescribing. Faculty and resident physicians were
      surveyed before and after the intervention to assess their attitudes. Patients
      who received naloxone kits were surveyed to assess their attitudes and use of
      opioids and naloxone. RESULTS: Over 16 months, 71 outreach letters were
      distributed and 97 naloxone kits were dispensed. The majority of kits were
      prescribed for illicit opioid use. Faculty and resident physician surveys
      indicated improved knowledge about naloxone prescribing, and increased
      professional satisfaction caring for patients requesting opioids. Surveyed
      patients endorsed high levels of comfort discussing opioid use with their primary
      care physician. Five successful opioid overdose reversals were reported.
      CONCLUSIONS: An interprofessional naloxone counseling intervention engaged
      patients in opioid use discussions, increased provider satisfaction, and reversed
      overdoses. Improving naloxone access is an essential component of comprehensive
      overdose prevention programs that encourage responsible opioid prescribing and
      use.

PMID- 29045992
TI  - Teaching Family Meeting Skills Makes a Difference.

PMID- 29045994
TI  - She Died Alone.

PMID- 29045995
TI  - Ingesting A Sports Drink Enhances Simulated Ice Hockey Performance While Reducing
      Perceived Effort.
AB  - This study determined whether ingesting a carbohydrate-electrolyte solution (CES)
      vs. progressive dehydration affected skeletal muscle glycogen use and performance
      in ice hockey players during simulated ice hockey exercise comprised of 3 active
      "periods". Seven males (21.3+/-0.3 years, 184.7+/-1.2 cm, 84.2+/-3.9 kg, and
      49.6+/-1.8 mL.kg-1.min-1) performed a hockey-specific protocol on two occasions
      and either dehydrated progressively (NF), or stayed well-hydrated by ingesting a
      CES. Muscle biopsies were taken at rest, before the 3rd period (P3), and after
      the final sprint in the protocol. Compared to dehydration in the NF trial (-1.8%
      BM), CES ingestion enhanced voluntary performance (151.0+/-8.0 vs. 144.1+/-8.7
      kJ) and glycogen use (177.5+/-31.1 vs. 103.5+/-16.2 mmol.kg dm-1), and reduced
      perceived exertion (16+/-1 vs. 18+/-1) in P3. Mean core temperature was reduced
      by CES ingestion throughout the protocol (38.0+/-0.2 vs. 38.1+/-0.1 degrees C).
      These results suggest that compared to progressive dehydration, staying hydrated
      by ingesting a CES helps preserve performance, while reducing thermal and
      perceptual strains, in P3 of cycle-based simulation of ice hockey exercise. These
      benefits are observed despite greater glycogen use in P3 with CES ingestion.

PMID- 29045996
TI  - SICKO. Development of a Multi-Disciplinary Training-Concept for Paediatric
      Oncology.
AB  - Background Treating children with cancer requires multiple different skills. For
      the healthcare personnel (HCP) in Germany the practice of ongoing training to
      improve professional skills is almost non-existent. Therefore, we developed a
      programme called 'SICKO' to support HCPs skills and attitudes by means of a
      multidisciplinary workshop. Methods Following a qualitative analysis, we then
      designed a modular (3 day) workshop. During day one (8 h) participants learn
      practical skills, the fundamentals of chemotherapy, and effective communication
      skills. Workshop day 2 (8 h) includes education regarding the complications of
      cancer therapy (e. g. tumour-lysis syndrome, delayed methotrexate excretion), and
      their management. Topics during day 3 (8 h) include 'breaking bad news', conflict
      management in the team, infusion-related complications and 'crew resource
      management' (CRM). Results 43 nurses and 33 physicians participated between 2013
      and 2015. All participants highly recommend the workshop. Participants felt that
      knowledge increased significantly after workshops and were more confident
      regarding challenging communications. Discussion/Conclusions Although long-term
      effects have not yet been evaluated, 'SICKO' offers the opportunity for HCP to
      train and experience simulated day-to-day challenges in the field of paediatric
      oncology.

PMID- 29045997
TI  - The Influence of BIS Monitoring on Sedative Dose in Pediatric Patients Undergoing
      Open Muscle Biopsies - a Randomized Controlled Trial.
AB  - BACKGROUND: The use of Propofol and Remifentanil for analgosedation in children
      is common and safe. For sedation monitoring clinical scores as Comfort Score (CS)
      as well as bispectral index (BIS) are frequently applied. The impact of BIS for
      sedation monitoring in pediatric patients is still under debate. This prospective
      study aims to investigate whether dual sedation monitoring of CS and BIS compared
      with monitoring of CS alone during muscle biopsies in children can reduce
      sedative doses, reduce awakening time and prevent complications. METHODS: 50
      pediatric patients requiring sedation for open muscle biopsy were prospectively
      enrolled. Analgosedation was performed with remifentanil and propofol. Patients
      were randomly assigned to 2 groups: In 25 patients, sedation was monitored using
      CS alone, and in 25 patients CS and BIS monitoring were simultaneously applied.
      The primary outcome was the propofol dose applied during muscle biopsy. Secondary
      outcome parameters were recovery time and the frequency of complications.
      RESULTS: The median CS during the intervention in both groups was equal (11,
      P=1.000). The median BIS in group 2 was 59. No complications occurred in either
      group. There was no difference in propofol dose in either group (8.4 vs. 7.2
      mg/kg/h; P=0.58) and no difference in the duration until eye opening (9 vs. 11
      min; P=0.081). CONCLUSION: For children undergoing minor surgical procedures
      under analgosedation, BIS monitoring does not affect the sedative dose, the time
      until eye opening or the frequency of complications.

PMID- 29045998
TI  - [Plastic reconstructive microsurgery in the elderly patient - Consensus statement
      of the German Speaking Working Group for Microsurgery of the Peripheral Nerves
      and Vessels].
AB  - During the last two decades, understanding and experience of microsurgical
      reconstruction have increased. This is linked to improved instruments and
      technical devices, as well as to the increased number of available donor sites
      for microvascular flap transfer. If the indication is appropriate, it is now
      possible to perform personalised, safe and successful microsurgical
      reconstructions, almost independently of the patients' age. Despite these
      constant developments, there is little specific literature on microsurgery
      related to the specific problems of the elderly patient. During two consensus
      workshops organised by the DAM (German Speaking Working Group for Microsurgery of
      the Peripheral Nerves and Vessels), the latest findings and experience with
      microsurgical reconstruction in the elderly patient were presented by a group of
      experts and current recommendations were formulated. On the basis of these
      consensus workshops and the current literature, this article discusses important
      issues in this area.

PMID- 29045999
TI  - [Coronary Heart Disease: Advances in Diagnostics and Therapy].

PMID- 29046000
TI  - [84-Year-Old Woman with Onesided Leg Weakness].

PMID- 29046001
TI  - [Different Symptoms and Course of Coronary Heart Disease in Men and Women].
AB  - According to the federal statistical office, cardiovascular disorders are still
      the leading cause of death in Germany. Chronic ischemic heart disease and acute
      myocardial infarction are the most important subgroups. In addition to evidence
      based and personalized medicine, in recent years gender medicine has been
      established as an independent research area. Gender differences are evident in
      the majority of prevalent diseases, including cardiovascular disorders. The
      following article provides an insight into the diagnostically and therapeutically
      specific aspects of coronary heart disease in men and women.

PMID- 29046002
TI  - [Optimal Diagnostics and Therapy for Microvascular Angina Pectoris].
AB  - Patients with microvascular angina are characterized by angina pectoris with
      proof of myocardial ischemia in the absence of any relevant epicardial stenosis
      and without myocardial disease (type 1 coronary microvascular dysfunction
      according to Crea and Camici). Structural and functional alterations of the
      coronary microvessels (diameter < 500 um) are the reason for this phenomenon.
      Frequently such alterations are associated with cardiovascular risk factors.
      Patients with angina pectoris without epicardial stenoses represent for 10 - 50 %
      of all patients undergoing coronary angiography depending on the clinical
      presentation. Diagnostic approaches include non-invasive (e. g. combination of
      coronary CT-angiography and positron emission tomography/echo Doppler-based
      coronary flow reserve measurements) as well as invasive procedures (coronary flow
      reserve measurements in response to adenosine, intracoronary acetylcholine
      testing). Pharmacological treatment of these patients is often challenging and
      should be based on the characterization of the underlying mechanisms. Moreover,
      strict risk factor control and individually titrated combinations of antianginal
      substances (e. g. beta blockers, calcium channel blockers, nitrates, ranolazine,
      ivabradine etc.) are recommended.

PMID- 29046003
TI  - [FFR-Guided Revascularisation - Pros and Cons].
AB  - An invasive measurement of the fractional flow reserve (FFR) allows the valuation
      of the individual risk for ischemic events in patients with coronary artery
      disease. Therefore, FFR has become a valuable tool to guide coronary
      revascularisations. The cut-off value <= 0.80 has been validated in many
      different subsets of patients. However, FFR values describe a risk continuum with
      an inverse correlation between FFR value and the risk of events. So FFR should
      always be interpreted regarding the patient's clinical context, especially in
      patients with a high risk for rapid disease progression. As such, patients with
      diabetes mellitus and deferred revascularisation based on FFR > 0.80 had worse
      clinical outcomes compared to patients without diabetes. In addition, FFR shows
      methodical deficiencies concerning the quantification of serial stenoses as well
      as the valuation of residual ischemia of the culprit vessel early after
      myocardial infarction. This article highlights both the strengths and the
      pitfalls in the use and interpretation of FFR.

PMID- 29046004
TI  - [Coronary Computed Tomography Angiography in Patients with Stable Coronary Artery
      Disease].
AB  - The guidelines on the management of stable coronary artery disease (SCAD)
      recommend the use of coronary computed tomography angiography (CTA) in the
      process of diagnosing coronary artery disease in patients with low intermediate
      pre-test probability for SCAD. Particularly in cases where stress
      electrocardiogram or stress imaging provides unclear results, a computed
      tomographic examination can be considered as a reliable alternative to invasive
      coronary angiography. Due to its high negative predictive value, coronary CTA can
      provide accurate information on the presence of coronary artery stenosis and thus
      coronary artery disease can be reliably excluded without the risks associated
      with invasive procedures. Similarly, patients with unstable angina or chest pain
      without typical alterations in the electrocardiogram and without an elevation of
      troponin can also benefit from a non-invasive coronary CTA-based diagnostics as
      first approach as it allows ruling out the presence of disease or planning an
      intervention without the risks associated with a potentially inappropriate
      invasive approach.

PMID- 29046005
TI  - [Coronary Computed Tomography Instead of Catheter Angiography? - No!]
AB  - The need for coronary computed tomography (CTA) is still a matter of discussion.
      Areas in which CTA can replace invasive coronary angiography are rare. More data
      is needed to precise in which clinical settings CTA might be beneficial.

PMID- 29046006
TI  - [Skin and Soft Tissue Infections Due to Corynebacterium ulcerans - Case Reports].
AB  - History and clinical findings We report on three patients suffering from skin and
      soft tissue infections of the legs due to toxigenic Corynebacterium ulcerans
      strains. In all three patients, there was a predisposition due to chronic
      diseases. Three patients had domestic animals (cat, dog) in their households.
      Investigations and diagnosis A mixed bacterial flora including Corynebacterium
      ulcerans was found in wound swab samples. Diphtheric toxin was produced by the
      Corynebacterium ulcerans strains in all three cases. Treatment and course In all
      three patients, successful handling of the skin and soft tissue infections was
      possible by combining local treatment with antibiotics. Diphtheria antitoxin was
      not administered in any case. Conclusion Based on a review of the recent
      literature pathogenesis, clinical symptoms and signs, diagnostics and therapy of
      skin and soft tissue infections due to Corynebacterium ulcerans are discussed.
      Corynebacterium ulcerans should be considered as a potential cause of severe skin
      and soft tissue infections. Occupational or domestic animal contacts should be
      evaluated.

PMID- 29046007
TI  - [Dietary Recommendations in Metabolic Vascular Syndrome].
AB  - Cardiovascular disease is the number one cause of death globally. Poor diet
      constitutes a key factor in the initiation and progression of cardiovascular
      disease and has become the leading risk factor for disability and death
      worldwide. Therefore, addressing suboptimal nutrition is of key prognostic
      relevance in primary and secondary prevention of metabolic vascular
      syndrome.Metabolic vascular syndrome is a multidimensional network of acquired
      cardiometabolic risk factors closely related to insulin resistance (IR) and
      concomitant hyperinsulinemia. IR, being the underlying cause of metabolic
      vascular syndrome and certain types of cancer, should attract the attention of
      every clinician. As changes in lipoprotein metabolism are one of the earliest
      indicators of metabolic dysfunction, a relevant biomarker for identifying
      individuals with IR is the TAG/HDL-C ratio.IR - and concomitant metabolic
      vascular risk - can be effectively treated by lifestyle intervention. If IR is
      present, dietary carbohydrate restriction has consistently been shown to be
      superior to dietary fat restriction in reversing metabolic dysfunction. The
      beneficial effects of carbohydrate restricted diets on metabolic vascular risk
      are independent of BMI - diet quality therefore confers patient benefit beyond
      weight reduction.The effect of single nutrients on isolated lipid surrogate
      markers such as LDL-C does not capture their global effect on metabolic vascular
      risk.Targeting IR with a low glycemic load, real food diet will reduce overall
      energy density and will improve all risk factors of metabolic vascular syndrome.
      In particular, replacing refined carbohydrates with healthy fats in the context
      of a Mediterranean style-, low carbohydrate and calorie-unrestricted dietary
      pattern has been shown to significantly reduce burden of metabolic vascular
      disease.

PMID- 29046008
TI  - [Severe Hemorrhagic Shock in a 93-Year Old Patient due to a Diagnostic
      Thoracocentesis].
AB  - An intercostal artery laceration is a rare iatrogenic complication following
      thoracocentesis and concerns especially elderly patients. We report a case of a
      severe hemorrhagic shock in a 93-year old patient due to diagnostic
      thoracocentesis.

PMID- 29046010
TI  - [Differential Diagnosis of Mediastinal and Hilar Lymphadenopathy with Focus on
      Occupational Diseases].
AB  - Hilar and mediastinal lymphadenopathy may represent a diagnostic challenge in
      clinical practice. This article is intended to facilitate differential diagnosis
      by a systematic description of relevant pathologies, notably with occupational
      etiology. Clinical findings of relevant diseases, i. e. of tuberculosis, chronic
      beryllium disease, sarcoidosis, lung cancer, malignant lymphoma, Epstein-Barr
      virus infection, and histoplasmosis are compared.Case history, imaging and
      laboratory tests have important diagnostic impact. But also invasive methods can
      be necessary in order to exclude and prove malignancy, infection or autoimmune
      disease.

PMID- 29046009
TI  - [Experiences of Patients with Invasive and Non-Invasive Home Mechanical
      Ventilation - a Systematic Review of Qualitative Research].
AB  - AIM OF THE STUDY:  Human beings can be ventilated outside of a hospital after a
      lung failure or due to a neurodegenerative disease. This can be done in different
      living conditions. This article examines the question of what experiences such
      patients have made with invasive home mechanical ventilation, and how they have
      adapted their new lives. METHODOLOGY:  On the basis of a systematic literature
      research, qualitative studies were analyzed that depict the social reality of
      patients with invasive and non-invasive home mechanical ventilation. RESULTS: 
      Eleven international studies with a qualitative research design could be
      identified. Studies that investigate the experiences of patients with invasive
      ventilation in Germany have not yet been published. The analysis led to the
      following topics: experiencing the start of ventilation, living with ventilation,
      safety, family life, stigmatization and a life with dependence, but self
      determined. CONCLUSION:  Human beings who need to be out of hospital an invasive
      or non-invasive ventilation, it is difficult to decide for the ventilation and
      the right time to begin it. With the ventilation, they then connect a positive
      feeling of life. To enable a self-determined and active life to humans with
      invasive ventilation, it is important for health care providers to know the needs
      and to adapt to them individually.

PMID- 29046011
TI  - [Biomarkers in Diagnosis, Treatment and Prognosis of Infectious Lung Diseases].
AB  - Biomarkers play an important role in the management of infectious pulmonary
      diseases, even though there is only limited evidence that biomarker-guided
      therapies are superior to clinical strategies.Well-established indications for
      the use of biomarkers are the guidance of the duration of antibiotic therapy in
      community-acquired pneumonia (CAP) by PCT, the decision against the use of
      antibiotics by CRP or PCT in ambulatory settings, and the evaluation of CAP
      treatment by CRP or PCT kinetics.In the prognostic assessment of CAP, the
      standard biomarkers of acute organ dysfunction should be given priority, e. g.
      leukocyte and platelet counts, creatinine/urea and lactate, in combination with
      clinical signs and symptoms.MR-pro-ADM could enrich diagnostics in the future.
      Genetic transcriptome analysis is a completely new and promising concept.

PMID- 29046012
TI  - Root aneurysm following aortic valve replacement 20 years after an arterial
      switch operation.
AB  - Late development of annuloaortic ectasia (AAE) and progression of aortic
      regurgitation (AR) are widely recognized outcomes following an arterial switch
      operation (ASO). We treated a 29-year-old male with AAE and rapid aortic root
      expansion, who underwent ASO as a neonate and aortic valve replacement (AVR) as
      an adult. He was diagnosed as having dextro-(D-loop) transposition of the great
      arteries after birth and underwent ASO at the age of 13 months. At the age of 19
      years, AVR was performed for progressive AR. AAE developed after AVR. In patients
      who have undergone neonatal ASO, AAE may occur following AVR decades later.

PMID- 29046013
TI  - New insights into cardiotoxicity caused by chemotherapeutic agents.
AB  - LINKED ARTICLES: This article is part of a themed section on New Insights into
      Cardiotoxicity Caused by Chemotherapeutic Agents. To view the other articles in
      this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.21/issuetoc.

PMID- 29046014
TI  - Tomato CRY1a plays a critical role in the regulation of phytohormone homeostasis,
      plant development, and carotenoid metabolism in fruits.
AB  - Blue light photoreceptors, cryptochromes (CRYs), regulate multiple aspects of
      plant growth and development. However, our knowledge of CRYs is predominantly
      based on model plant Arabidopsis at early growth stage. In this study, we
      elucidated functions of CRY1a gene in mature tomato (Solanum lycopersicum) plants
      by using cry1a mutants and CRY1a-overexpressing lines (OE-CRY1a-1 and OE-CRY1a
      2). In comparison with wild-type plants, cry1a mutants are relatively tall,
      accumulate low biomass, and bear more fruits, whereas OE-CRY1a plants are short
      stature, and they not only flower lately but also bear less fruits. RNA-seq, qRT
      PCR, and LC-MS/MS analysis revealed that biosynthesis of gibberellin, cytokinin,
      and jasmonic acid was down-regulated by CRY1a. Furthermore, DNA replication was
      drastically inhibited in leaves of OE-CRY1a lines, but promoted in cry1a mutants
      with concomitant changes in the expression of cell cycle genes. However, CRY1a
      positively regulated levels of soluble sugars, phytofluene, phytoene, lycopene,
      and beta-carotene in the fruits. The results indicate the important role of CRY1a
      in plant growth and have implications for molecular interventions of CRY1a aimed
      at improving agronomic traits.

PMID- 29046015
TI  - Magnesium Sulfate as an Adjuvant to Anesthesia in Patients with Arterial
      Hypertension
AB  - There is limited evidence showing that elevated arterial blood pressure in
      surgicalpatients may be associated with increased perioperative risk; however,
      cardiovascular instability frequentlyoccurs during anesthesia. The most commonly
      used anesthetic agents, both intravenous andinhalation ones, produce a decrease
      in arterial blood pressure. Magnesium, acting as a natural calcium
      channelblocker, induces direct and indirect vasodilatation, thus playing a role
      in the treatment of arterialhypertension. In this research, we assessed the
      effects of magnesium sulfate on cardiovascularstability in patients undergoing
      diverse planned surgical procedures (abdominal, orthopedic, urology)under general
      balanced anesthesia, who were diagnosed with arterial hypertension grade 1 and 2.
      Theresearch encompassed 100 patients of both sexes, aged from 20 to 65.
      Immediately before inductionof anesthesia with propofol, the patients in the
      experimental group (50 study subjects) received 30 mg/kg bolus dose and magnesium
      sulfate infusion at 10 mg/kg/h, whereas the subjects in the controlgroup (50
      patients) were administered normal saline. Anesthesia was achieved and maintained
      withsevoflurane, fentanyl and rocuronium. The hemodynamic variables of mean
      arterial pressure and heartrate were measured every five minutes, starting
      immediately before magnesium infusion. Statisticalanalysis of the categorized
      values of mean arterial pressure and heart rate revealed a statistically
      significant between-group difference at 60th and 90th minute of anesthesia. In
      conclusion, magnesiumsulfate as an adjuvant to anesthesia in patients with
      arterial hypertension reduces hemodynamicchanges during anesthesia.

PMID- 29046016
TI  - Transient Obstructive Hydrocephalus in Patients with Intracerebral Hemorrhage:
      Report of Two Cases
AB  - Obstructive hydrocephalus is a relatively common complication of
      intraventricularhemorrhage resulting in high morbidity and mortality. We report
      two cases of transient obstructivehydrocephalus caused by obstruction of
      mesencephalic duct in patients that presented with alteredconsciousness which
      resolved spontaneously in a few hours. In very rare cases, obstructive
      hydrocephalusdue to intraventricular hemorrhage may be transient and does not
      need neurosurgical orinvasive procedures for lowering raised intracranial
      pressure, which otherwise are currently preferredtreatment options.

PMID- 29046017
TI  - Pneumothorax and Pneumomediastinum as a Rare Complication of Laparoscopic Surgery
AB  - Occurrence of bilateral pneumothorax, pneumomediastinum and subcutaneousemphysema
      during gynecologic laparoscopic procedure is very rare. We report a case of a 23
      year-oldwoman who developed bilateral pneumothorax, pneumomediastinum and
      subcutaneous emphysemaduring laparoscopic ovarian cystectomy. Carbon dioxide
      extravasations outside the peritoneal cavityduring laparoscopy may have fatal
      consequences. Careful monitoring, immediate diagnosis and propertreatment are
      crucial for patient safety.

PMID- 29046018
TI  - OSTEOID OSTEOMA OF THE CORACOID PROCESS: CASE REPORT WITH LITERATURE REVIEW.
AB  - Osteoid osteoma (OO) is the most common benign osteogenic bone tumor
      thatpredominantly affects young adults. OO is commonly localized in long bones,
      and therefore, it israrely considered in differential diagnosis of chronic
      shoulder pain. We report a case of a 22-year-oldmale athlete, without history of
      previous trauma, who presented to our Department with chronicshoulder pain, which
      escalated during the night and responded to nonsteroidal anti-inflammatorydrug
      treatment. Considering these typical symptoms, diagnostic pathway was immediately
      directedtowards OO, with magnetic resonance and computed tomography confirming
      the diagnosis of OO ofthe coracoid process (CP). Since neurovascular structures
      are in the proximity of CP, and this verydelicate area does not support
      radiofrequency ablation, we decided to perform an open procedure withdrilling of
      the lesion and excochleation. The pain withdrew immediately after the procedure,
      and onsix-month follow up the patient remained pain free. In the treatment of OO
      of the CP, we recommendopen surgical procedure with tumor ablation by drilling
      instead of CP resection, presenting a safe,simple and low-cost method that
      simultaneously completely destroys the lesion and preserves theanatomical and
      functional role of CP

PMID- 29046019
TI  - Osteoid Osteoma of the Coracoid Process: Case Report with Literature Review
AB  - Osteoid osteoma (OO) is the most common benign osteogenic bone tumor
      thatpredominantly affects young adults. OO is commonly localized in long bones,
      and therefore, it israrely considered in differential diagnosis of chronic
      shoulder pain. We report a case of a 22-year-oldmale athlete, without history of
      previous trauma, who presented to our Department with chronicshoulder pain, which
      escalated during the night and responded to nonsteroidal anti-inflammatorydrug
      treatment. Considering these typical symptoms, diagnostic pathway was immediately
      directedtowards OO, with magnetic resonance and computed tomography confirming
      the diagnosis of OO ofthe coracoid process (CP). Since neurovascular structures
      are in the proximity of CP, and this verydelicate area does not support
      radiofrequency ablation, we decided to perform an open procedure withdrilling of
      the lesion and excochleation. The pain withdrew immediately after the procedure,
      and onsix-month follow up the patient remained pain free. In the treatment of OO
      of the CP, we recommendopen surgical procedure with tumor ablation by drilling
      instead of CP resection, presenting a safe,simple and low-cost method that
      simultaneously completely destroys the lesion and preserves theanatomical and
      functional role of CP.

PMID- 29046020
TI  - Botryoid Cyst, a Rare Type of Odontogenic Cyst
AB  - Botryoid cyst, a rare type of odontogenic cyst, is usually considered a
      multilocularvariant of lateral periodontal cyst. It was first described in 1973,
      and up to the present less than ahundred cases have been reported in the
      literature. Botryoid cysts are characterized by a multilocularhistologic finding
      and a higher risk of recurrence than lateral periodontal cysts. In this article,
      we presenta case of botryoid cyst from our clinical practice, accompanied by
      literature review of previouscases reported in the literature so far. Study
      results showed that botryoid cysts mostly affected populationin their fifties,
      with a slight female (53.5%) predominance over males (46.5%). The mandible wasthe
      most frequently affected region, accounting for 70 (83.3%) cases. Maxilla was
      only sporadicallyaffected accounting for 14 (16.7%) cases. Radiographic
      appearance of botryoid cysts can be multilocularor unilocular. It is concluded
      that the recurrence rate is relatively high (30.1%), therefore longterm follow up
      is needed.

PMID- 29046021
TI  - When Cardiovascular Complications Occur in Young Patients With Type 1 Diabetes
      Mellitus and How Should We Demonstrate It?

PMID- 29046022
TI  - [Prevalence of allergic rhinitis and its symptoms in the school children
      population of Cuernavaca, Morelos, Mexico].
AB  - BACKGROUND: Studies on allergic rhinitis prevalence have found significant
      variations in their results, even in closely-living populations. OBJECTIVE: To
      determine and compare the prevalence of allergic rhinitis and its symptoms in
      schoolchildren from Cuernavaca, Morelos, Mexico. METHODS: Cross-sectional,
      descriptive study on the prevalence of allergic rhinitis diagnosis and symptoms,
      where the "Diagnostic questionnaire for epidemiological studies" was used between
      June and December 2015 in pre-school and primary and secondary school population,
      after authorization was granted by parents and school authorities. RESULTS: In
      7866 surveys in a population aged between 3 and 15 years, 939 cases of allergic
      rhinitis (11.94%) were identified, with 53% belonging to the female gender. The
      symptom with the highest prevalence was cold-induced nasal congestion (56.8%),
      followed by rhinitis accompanied by ocular symptoms (35.8%) and recurrent flu
      like symptoms (20), which was the most common symptom in allergic rhinitis
      (100%). CONCLUSION: A significant variation was observed in the prevalence of
      symptoms, notably higher than that of questionnaire-obtained allergic rhinitis
      diagnosis (11.94%), which suggests that the independent prevalence of symptoms is
      not a good parameter to detect the prevalence of allergic rhinitis.

PMID- 29046023
TI  - [Determination of a new cow's milk-based formula allergenic capacity in 7
      infants].
AB  - BACKGROUND: Cow's milk protein allergy is the main allergic problem during the
      first year of life, possibly owing to immune and gastrointestinal systems poor
      maturation. To prevent allergic reactions, the content and type of proteins in
      infant formulas resemble those of breast milk. We believe that reactions are due
      rather to the amount than to the type of protein. OBJECTIVE: To design a new
      formula with cow's milk that provides the infant with the main nutrients at an
      affordable cost and with lower risk for the development of allergies. METHODS:
      Three-phase project: product design, industrial production and ex vivo assay to
      assess for anemia and type I allergic reaction by CD63 expression in basophils.
      RESULTS: For every 100 calories, the content of protein was 2.0 g, carbohydrates
      7.2 g and fat 0.5 g, which is higher than the indicated maximum value (4.5 g).
      Microbiologically, it was an innocuous food. CD63 expression was low in 57.1% of
      the babies and high in 42.9%. CONCLUSION: The new formula did not trigger any
      allergenic responses and can therefore be supplied to non-atopic infants.

PMID- 29046024
TI  - Clinical impact in the real life of guidelines recommendations for atopic
      dermatitis in a tropical population (TECCEMA cohort).
AB  - BACKGROUND: Real-life impact of guidelines for the management of atopic
      dermatitis has been poorly studied. OBJECTIVE: To assess atopic dermatitis
      clinical control in residents of a tropical area managed according to
      international consensuses. METHODS: Prospective study with a 24-month follow-up.
      Clinical response was assessed with SCORAD, DLQI and a subjective scale (SS) on
      severity perception by the patient. RESULTS: Two-hundred and thirty-three
      patients were stratified according to SCORAD: 53 had mild severity (22%), 116
      moderate (49%) and 64 severe (27%). Baseline SCORAD mean was 33 (15-41), for
      DLQI, it was 14 (11-20), and for the subjective scale, 85% (67-99). At 6 months,
      there was significant reduction (p < 0.5): SCORAD 29 (14-41), DLQI 12 (8-16) and
      subjective scale 62% (45-80). At 2 years, SCORAD was 21 (9-34), DLQI 7 (4-10) and
      subjective scale 41% (27-56); only 33% achieved complete control (SCORAD < 15%,
      DLQI < 5, subjective scale < 20%). CONCLUSIONS: Following international
      guidelines' recommendations reduces eczema severity and improves quality of life,
      although only 33% achieved complete control after 2 years.

PMID- 29046025
TI  - [Asthma-associated oral and dental health repercussions in children aged 6 to 12
      years].
AB  - BACKGROUND: Asthma, which is characterized by mouth breathing and by the use of
      drugs for its treatment, affects between 1 and 30% of children and adolescents.
      There are only few studies reporting its impact on the oral cavity. OBJECTIVE: To
      find out the most common asthma-associated repercussions in 6 to 12-year-old
      children. METHODS: Cross-sectional, comparative, analytical study carried out in
      2 primary schools from Coclique, Veracruz, Mexico, in 6 to 12-year-old children.
      The International Study of Asthma and Allergies in Childhood (ISAAC)
      questionnaire for parents was used. RESULTS: In a population of 409 children, a
      prevalence of asthma of 6.84% (n = 28) was found, which was higher in males (15,
      54%); boys aged 6, 7 and 11 years and girls aged 8, 9 and 10 years were most
      affected. Risk factors for oral manifestations were acidic pH (OR = 170), caries
      (OR = 4.29), anterior open bite (OR = 66.78), gingivitis (OR = 9.75), atypical
      swallowing (OR = 15.70) and high-arched palate (OR = 45.60). CONCLUSION: Children
      with chronic conditions such as asthma require an oral and dental preventive
      program as part of their interdisciplinary care.

PMID- 29046026
TI  - [Influence of lifestyle, diet and vitamin D on atopy in a population of Afro
      descendant Colombian children].
AB  - BACKGROUND: Allergic conditions have shown an increase in the past few decades.
      Hygiene, changes in lifestyle, diet and vitamin D have been blamed for this
      increase. OBJECTIVE: To determine the role of environment, diet and vitamin D in
      atopic diseases in a population of Colombian Afro-descendant children. METHODS:
      Cross-sectional, descriptive, observational study in 200 Afro-descendant children
      of rural and urban areas from northern Colombia. Lifestyle and diet were
      established by questionnaires, atopy was assessed with skin tests and total and
      specific IgE and vitamin D levels were determined by ELISA. RESULTS: Results:
      Atopy was more prevalent in the urban population (24 % versus 7 %, p < 0.001).
      Blomia tropicalis was the most common allergen (80.6 %). The PCA indicated two
      dietary patterns. In the rural area children, the consumption of dairy products
      and fruit/vegetables was higher, and related with a protective effect on atopy
      (OR, 0.21 [p < 0.027] and OR, 0.11 [ p < 0.04]). A similar pattern was observed
      with total IgE and vitamin D levels (2450.73 versus 777.56 kU/mL [p < 0.01] and
      59.32 ng/mL versus 31.14 ng/mL [p < 0.001], respectively). CONCLUSION: Allergic
      conditions were less prevalent in rural area residents, possibly owing to higher
      consumption of unpasteurized dairy products and fruit/vegetables, as well as
      higher levels of vitamin D.

PMID- 29046027
TI  - [Frequency of skin reactivity to food allergens in allergic patients].
AB  - BACKGROUND: Food allergy is deemed to have a worldwide prevalence ranging from 2
      to 10 %. OBJECTIVE: To determine the frequency of skin reactivity to food
      allergens by age groups. METHODS: Cross-sectional, descriptive, prolective,
      observational study. Patients aged from 2 to 64 years with symptoms consistent
      with allergic disease were included. Skin prick tests were carried out with food
      allergens. Frequencies and percentages were estimated. RESULTS: One-hundred and
      ninety-one patients were included, out of which 63.4% were females. Mean age was
      22.5 years; 19.3 % showed positive skin reactivity to at least one food.
      Distribution by age group was as follows: preschool children 13.5 %,
      schoolchildren 24.3 %, adolescents 2.7 % and adults 59.5 %. Diagnoses included
      allergic rhinitis in 84.3 %, asthma in 19.4 %, urticaria in 14.1 % and atopic
      dermatitis in 8.4 %. Positive skin reactivity frequency distribution in
      descending order was: soybeans with 5.2 %, peach with 4.7 %, grapes, orange and
      apple with 3.6 %, nuts with 3.1 %, pineapple, avocado, tomato and tuna with 2.6
      %. CONCLUSION: The frequency of skin reactivity to food allergens was similar to
      that reported in the national and Latin American literature, but sensitization to
      each specific allergen varied for each age group.

PMID- 29046028
TI  - [ARIA 2016 executive summary: Integrated care pathways for predictive medicine
      throughout the life cycle in Argentina].
AB  - The ARIA initiative was started during a World Health Organization workshop in
      1999. The initial goals were to propose a new classification for allergic
      rhinitis, to promote the concept of multi-morbidity in asthma and rhinitis and to
      develop guidelines with stakeholders for world-wide use. ARIA is now focused on
      the implementation of emerging technologies for individualized and predictive
      medicine. MASK: MACVIA-Aria Sentinel Network uses mobile technology to develop
      care pathways that enable management by a multidisciplinary group or by patients
      themselves. An App for iOS and Android uses a visual analogue scale to assess
      symptom control and work productivity, as well as a clinical decision support
      system; it is associated with an interoperable tablet for health professionals.
      The escalation strategy uses recommendations of the European Innovation
      Partnership on Active and Healthy Ageing. The aim of ARIA's new approach is to
      provide an active and healthy life to people affected by rhinitis, regardless of
      age, gender or socioeconomic status, in order to reduce social and health
      inequalities caused by the disease.

PMID- 29046030
TI  - [Immunopathology of chronic obstructive pulmonary disease].
AB  - Chronic obstructive pulmonary disease (COPD) is a common, preventable and
      treatable condition that has a complex pathophysiology and an even more complex
      immunopathological process. The purpose of this review was to analyze COPD
      immunopathological aspects, which was addressed by undertaking a literature
      search for the most relevant documents indexed in the PubMed database over the
      last 10 years. Different conclusions could be drawn: in COPD immunopathology
      there are immune and non-immune inflammatory changes with oxidative stress
      imbalance, there are alterations in the protease/anti-protease ratio caused by
      direct and indirect genetic and epigenetic-environmental defects; COPD produces
      irreversible tissue damage and chronic inflammation with tissue repair
      alteration, which induces chronic obstruction of the airway, bronchitis and
      systemic damage. Most common resulting comorbidities include cardiovascular
      disease, metabolic syndrome, osteoporosis, depression, musculoskeletal
      dysfunction, increased biological age, lung cancer and other types of
      malignancies. In the conception of COPD, recognizing that it is a non
      transmittable and preventable disease is indispensable.

PMID- 29046029
TI  - [Is it possible for chronic urticaria diagnostic approach to be simplified? A
      clinical data checklist].
AB  - BACKGROUND: Existing clinical guidelines do not offer an efficient alternative
      for the collection of data on relevant clinical traits during history and
      physical of the patient with chronic urticaria. OBJECTIVE: Our aim was to provide
      a clinical data checklist together with its guide to allow for thorough
      information to be obtained and for a physical exam that identifies the main
      features and triggering factors of the disease to be carried out. METHODS: A
      search was conducted for relevant literature on chronic urticaria in Medline, the
      Cochrane library and PubMed. RESULTS: We developed an easy-to-use clinical data
      checklist with its corresponding clinical guide, comprised by 42 items based on
      two components: essential clues for history taking and chronic urticaria
      diagnosis (typical symptoms according to subgroups, etiology and laboratory
      results). Some components are the time of disease onset, wheals' duration, shape,
      size, color and distribution, associated angioedema, atopy, triggering factors
      and others. CONCLUSION: The clinical data checklist and its guide constitute a
      tool to focus, guide and save time in medical consultation, with the main purpose
      to aid physicians in providing better diagnosis and management of the disease.

PMID- 29046031
TI  - [Innate lymphoid cells and their role in immune response regulation].
AB  - Innate lymphoid cells (ILCs) are lymphocytes lacking antigen recognition
      receptors and become activated in response to cytokines and through microbe
      associated molecular pattern (MAMP) receptors. ILCs are found mainly in mucosal
      tissues and participate in the immune response against infections and in chronic
      inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these
      cells have analogue functions to those of immune adaptive response lymphocytes
      Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNgamma, protect against
      infections with intracellular microorganisms and are related to inflammatory
      bowel disease immunopathology. ILC-2 express GATA3, produce IL-4, IL-5, IL-13 and
      amphiregulin, protect against parasitic infections and are related to allergy and
      obesity immunopathology. ILC-3 express ROR(gammat), produce IL-17 and IL-22,
      protect against fungal infections and contribute to tolerance to intestinal
      microbiota and intestinal repair. They are related to inflammatory bowel disease
      and psoriasis immunopathology. In general terms, ILCs maintain homeostasis and
      coadjuvate in the protection against infections.

PMID- 29046032
TI  - [The research protocol VI: How to choose the appropriate statistical test.
      Inferential statistics].
AB  - The statistical analysis can be divided in two main components: descriptive
      analysis and inferential analysis. An inference is to elaborate conclusions from
      the tests performed with the data obtained from a sample of a population.
      Statistical tests are used in order to establish the probability that a
      conclusion obtained from a sample is applicable to the population from which it
      was obtained. However, choosing the appropriate statistical test in general poses
      a challenge for novice researchers. To choose the statistical test it is
      necessary to take into account three aspects: the research design, the number of
      measurements and the scale of measurement of the variables. Statistical tests are
      divided into two sets, parametric and nonparametric. Parametric tests can only be
      used if the data show a normal distribution. Choosing the right statistical test
      will make it easier for readers to understand and apply the results.

PMID- 29046033
TI  - [Solar urticaria. Case report and literature review].
AB  - BACKGROUND: Solar urticaria is a rare type of inducible urticaria characterized
      by wheal and erythema formation shortly after exposure to sunlight or to an
      artificial light source; its pathophysiology is not yet entirely understood. The
      treatment of choice, in addition to exposure avoidance, consists in antihistamine
      administration. CLINICAL CASE: This is the case of a 27-year-old woman with no
      personal history of allergic diseases and with a 2-year history of erythema and
      wheals in photo-exposed areas associated with sunlight exposure for periods
      longer than 10 minutes. A provocation test was carried out; she was started on
      fexofenadine at 4-fold the standard dose (720 mg/day). Six weeks later, a new
      challenge was carried out without the antihistamine being discontinued; the
      reaction was less severe, but she continued with erythema for the first 60
      minutes post-exposure. After 3 months on high-dose antihistamines, she referred
      marked improvement in her quality of life and tolerance to brief sunlight
      exposure (for less than 15 minutes). CONCLUSIONS: Solar urticaria is a rare
      process but with a high impact on the patient. The use of antihistamines
      partially relieves symptoms and allows better tolerance to lighting expositions.

PMID- 29046034
TI  - [Neurological manifestations in atypical Kawasaki disease].
AB  - BACKGROUND: Kawasaki disease (KD) is a type of systemic vasculitis of unknown
      etiology. Atypical Kawasaki disease is defined as that where there are signs and
      symptoms not corresponding to the classical criteria for this nosological entity.
      Children with atypical Kawasaki disease may present with acute abdominal
      symptoms, meningeal irritation, pneumonia or renal failure. CLINICAL CASES: We
      describe 4 children with ages ranging from 2 to 12 years who had atypical
      Kawasaki disease, with neurological and gastrointestinal symptoms as part of the
      systemic presentation of the disease. Treatment consisted of immunoglobulin and
      corticosteroids with good evolution. CONCLUSIONS: KD is a systemic vasculitis
      that can involve many territories. Atypical manifestations can mislead the
      clinician and delay diagnosis. Pediatricians and sub-specialists should be aware
      of these neurological manifestations in order to provide adequate and opportune
      treatment.

PMID- 29046035
TI  - [Laboratorial alteration preceding staphylococcal infection clinical
      manifestations after intestinal transplantation].
AB  - BACKGROUND: Hospital-acquired infection, often with Staphylococcus aureus, is an
      important complication in intestinal transplant. CLINICAL CASE: A 2-year-old girl
      underwent small bowel transplantation owing to a small bowel volvulus. On the
      first postoperative day, lymphocyte phenotypes, serum immunoglobulins and
      chemotactic and phagocytic activity of neutrophils were assessed in peripheral
      blood. A decrease in the ingestion phase of phagocytosis by neutrophils was
      identified, in comparison with the results of 20 healthy children. On the second
      day, the patient had low fever and, on the third, abdominal pain. In view of
      this, she underwent a laparotomy that revealed purulent ascites due to
      Staphylococcus aureus. Specific treatment resulted in rapid regression of the
      infectious condition and good evolution of the patient. CONCLUSIONS: A decrease
      in the ingestion stage of phagocytosis by neutrophils preceded staphylococcal
      purulent ascites clinical manifestations, and immunologic assessment contributed
      to early diagnosis and treatment of the infection. We believe evaluation of
      neutrophilic activity is important in patients undergoing intestinal
      transplantation in order for possible hospital-acquired infections to be early
      diagnosed.

PMID- 29046036
TI  - [Spontaneous pneumomediastinum and subcutaneous emphysema associated with
      bronchospasm in a woman with no history of asthma].
AB  - BACKGROUND: Spontaneous pneumomediastinum most relevant triggering events are
      cough, vomiting, nutritional problems, physical activity and use of inhaled
      drugs. Association of spontaneous pneumomediastinum with non-asthma-related
      bronchospasm is an infrequent event. CLINICAL CASE: This is the case of a 21-year
      old woman without personal or family history of asthma, allergic rhinitis or
      atopy who during late puerperium had 39  degrees C fever, paroxysmal cough and
      chest oppression of sudden onset, as well as wheezing and subcutaneous emphysema
      of the neck; she had no previous nasal symptoms. Chest X-ray revealed free air in
      the mediastinum and left lateral side of the neck. Possible cause of the
      condition was attributed to bronchospasm related to airway infection. Treatment
      was based on bronchodilators, systemic steroids and supplementary oxygen
      administration. The symptoms subsided after 48 hours. CONCLUSIONS: In the
      clinical case herein presented, spontaneous pneumomediastinum precipitating
      factor appeared to be paroxysmal cough associated with bronchospasm and, hence,
      we suggest for this entity to be suspected in patients even if there is no
      previous history of asthma.

PMID- 29046038
TI  - Corrigendum.

PMID- 29046037
TI  - Vitamin D and asthma in clinical practice: the impact on asthma control.

PMID- 29046039
TI  - Topical Review: Transitional Services for Teens and Young Adults With Attention
      Deficit Hyperactivity Disorder: A Process Map and Proposed Model to Overcoming
      Barriers to Care.
AB  - Objective: To provide a topical review of the personal vulnerabilities and
      systemic barriers facing transitional age young adults with attention-deficit
      hyperactivity disorder (ADHD), followed by a proposed model for overcoming those
      barriers. Methods: Drawing from a growing, but limited, literature on the topic,
      we outline a process map for identifying and troubleshooting barriers to care in
      this at-risk population. Results: Young adults with ADHD frequently lack the
      organizational skills, time management, prioritization, and persistence to manage
      their health care at an expected level of adult independence. These difficulties
      are compounded by a health-care system that has less time or fewer resources for
      supporting young adult patients. Conclusions: Recommendations for easing the
      transition from pediatric to adult care for late adolescents with ADHD include
      heavily leveraging the doctor-patient relationship, and capturing the young
      adult's attention through technologies that already absorb them.

PMID- 29046040
TI  - Editorial: The Journal of Pediatric Psychology, 2013-2017: Editor's Vale Dictum.

PMID- 29046042
TI  - Commentary: The Science of Adolescent and Young Adult Health: A Growing Field and
      the Team Science Behind It.

PMID- 29046041
TI  - Development and Content Validation of the Transition Readiness Inventory Item
      Pool for Adolescent and Young Adult Survivors of Childhood Cancer.
AB  - Objective: The development of the Transition Readiness Inventory (TRI) item pool
      for adolescent and young adult childhood cancer survivors is described, aiming to
      both advance transition research and provide an example of the application of NIH
      Patient Reported Outcomes Information System methods. Methods: Using rigorous
      measurement development methods including mixed methods, patient and parent
      versions of the TRI item pool were created based on the Social-ecological Model
      of Adolescent and young adult Readiness for Transition (SMART). Results: Each
      stage informed development and refinement of the item pool. Content validity
      ratings and cognitive interviews resulted in 81 content valid items for the
      patient version and 85 items for the parent version. Conclusions: TRI represents
      the first multi-informant, rigorously developed transition readiness item pool
      that comprehensively measures the social-ecological components of transition
      readiness. Discussion includes clinical implications, the application of TRI and
      the methods to develop the item pool to other populations, and next steps for
      further validation and refinement.

PMID- 29046043
TI  - Introduction to the Special Issue on Adolescent and Young Adult Health: Why We
      Care, How Far We Have Come, and Where We Are Going.
AB  - This special issue on adolescent and young adult (AYA) health comprises 15
      original articles. The special issue recognizes the importance of AYA-focused
      research, highlights unique issues across the AYA period, and showcases cutting
      edge research focused on AYAs. We describe the rationale for focusing on the AYA
      population, themes of the special issue, and future directions.

PMID- 29046044
TI  - Lipidomics profiling reveals the role of glycerophospholipid metabolism in
      psoriasis.
AB  - Psoriasis is a common and chronic inflammatory skin disease that is complicated
      by gene-environment interactions. Although genomic, transcriptomic, and proteomic
      analyses have been performed to investigate the pathogenesis of psoriasis, the
      role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids
      not only comprise the bulk of the cellular membrane bilayers but also regulate a
      variety of biological processes such as cell proliferation, apoptosis, immunity,
      angiogenesis, and inflammation. In this study, an untargeted lipidomics approach
      was used to study the lipid profiles in psoriasis and to identify lipid
      metabolite signatures for psoriasis through ultra-performance liquid
      chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90
      participants (45 healthy and 45 psoriasis patients) were collected and analyzed.
      Statistical analysis was applied to find different metabolites between the
      disease and healthy groups. In addition, enzyme-linked immunosorbent assay was
      performed to validate differentially expressed lipids in psoriatic patient
      plasma. Finally, we identified differential expression of several lipids
      including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC),
      phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA);
      among these metabolites, LPA, LysoPC, and PA were significantly increased, while
      PC and PI were down-regulated in psoriasis patients. We found that elements of
      glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were
      significantly altered in the plasma of psoriatic patients; this study
      characterizes the circulating lipids in psoriatic patients and provides novel
      insight into the role of lipids in psoriasis.

PMID- 29046045
TI  - Comparative Study of Clinical and Radiographic Outcomes of High Tibial Osteotomy
      in Patients with Kissing Lesions and Non-Kissing Lesions.
AB  - Purpose: High Outerbridge grade lesions of the articular cartilage have been
      associated with poor outcomes of high tibial osteotomy (HTO). However, there has
      been no report on the efficacy of HTO in the presence of kissing lesions. The
      purpose of this study was to compare clinical and radiographic outcomes of HTO
      between kissing lesion and non-kissing lesion groups. Materials and Methods: Of
      the patients with medial compartment osteoarthritis and varus deformity treated
      with HTO between 2007 and 2012, 21 cases with kissing lesions and 22 cases
      without kissing lesions were selected. Clinical outcomes were assessed using the
      Lysholm knee scoring scale score, visual analogue scale score, Hospital for
      Special Surgery score, Western Ontario and McMaster Universities score, and
      Tegner activity score. Radiographic outcomes were assessed using the femoral
      tibial angle, mechanical axis deviation, medial proximal tibial angle, posterior
      tibial slope angle, and joint space width. Results: Clinical outcomes were
      improved in both groups from the postoperative assessment to the final follow-up,
      which showed no statistically significant difference between groups at the final
      follow-up. No statistically significant differences were observed with regard to
      radiographic assessment. Conclusions: Since both groups showed favorable short
      term clinical and radiographic outcomes, HTO might be an alternative treatment
      option for degenerative osteoarthritis with kissing lesions in relatively young
      patients.

PMID- 29046046
TI  - Three-Dimensional Evaluation of Similarity of Right and Left Knee Joints.
AB  - Purpose: The purpose of this study was to evaluate the anatomical similarity of
      three-dimensional (3D) morphometric parameters between right and left knees.
      Materials and Methods: Ten fresh-frozen paired cadaveric knees were tested.
      Following dissection, footprint areas of the anterior cruciate ligament (ACL) and
      posterior cruciate ligament (PCL) were measured. Surface scanning was performed
      using a 3D scanner. Scanned data were reproduced and morphometric parameters were
      measured on specialized software. After making mirror models, we compared
      footprint center positions of the ACL and PCL of both sides and calculated the
      average deviation of 3D alignment between the right- and left-side models.
      Results: No significant side-to-side differences were found in any morphometric
      parameters. Bony shapes displayed a side-to-side difference of <1 mm. Distal
      femoral and proximal tibial volumes did not present side-to-side differences,
      either; the average 3D deviations of alignment between the right and left sides
      were 0.8+/-0.4/1.1+/-0.6 mm (distal femur/proximal tibia). Center-to-center
      distances between the right and left ACL footprints were 2.6/2.7 mm (femur/tibia)
      for the anteromedial bundle and 2.4/2.8 mm for the posterolateral bundle. They
      were 1.9/1.5 mm for the anterolateral bundle and 2.2/1.8 mm for the posteromedial
      bundle of the PCL. Conclusions: There was a remarkable 3D morphometric similarity
      between right and left knees. Our results might support the concept of obtaining
      morphologic reference data from the uninvolved contralateral knee.

PMID- 29046047
TI  - Apoptosis pattern and alterations of expression of apoptosis-related factors of
      supporting cells in Kolliker's organ in vivo in early stage after birth in rats.
AB  - Kolliker's organ is a temporary but indispensable structure in the development of
      the cochlea. Supporting cells (SCs) within it release adenosine 5'-triphosphate
      (ATP), which may play a crucial role in cochlear development before the onset of
      hearing. To reveal the apoptosis of Kolliker's organ in new-born rats, we studied
      the morphological changes and expression of apoptosis-related factors during
      early postnatal development. We found SCs in Kolliker's organ decreased in number
      and changed in appearance along the cochlea apex-to-base gradient, and the
      expression of caspase-3, caspase-8, caspase-9 and bcl-2 in Kolliker's organ of
      the cochlea fluctuated along the course of postnatal development, with an
      expression peak at postnatal day 3. This study demonstrates a time-dependent
      degeneration of Kolliker's organ during postnatal cochlea development, which
      might be triggered by endogenous factors.

PMID- 29046048
TI  - Bone morphogenetic protein-4 and bone morphogenetic protein receptors expressions
      in the adult rat eye.
AB  - We investigated the expressions of bone morphogenetic protein-4 (BMP4) and its
      receptors, bone morphogenetic protein receptor IA (BMPRIA), bone morphogenetic
      protein receptor IB (BMPRIB) and bone morphogenetic protein receptor II (BMPRII)
      in the adult rat eye. Interesting differences in expression profile were observed
      between BMPRIA and BMPRIB in the retina. BMPRIA-like immunoreactivity (IR) was
      very intensely seen in the photoreceptor layer, while BMPRIB-IR was mainly
      observed in the other layers. In the cornea, BMP4, BMPRIA, BMPRIB and BMPRII-IRs
      were abundantly seen in the cell body of basal cells in the corneal epithelium,
      and endothelium. In the lens, BMP4, BMPRIA, BMPRIB and BMPRII-IRs were observed
      in epithelial cells, lens cortical fiber cells, however they were not seen in the
      capsule and the central region of the lens. In the iris and ciliary body, strong
      BMP4 and BMPRIB-IRs were observed in nonpigmented epithelium. These results
      suggest that different kinds of BMP signaling should be needed in different areas
      in the adult eye to keep the shapes, differentiation levels, and functions of
      various cells.

PMID- 29046049
TI  - Treatment of diabetic foot ulcers with Therapeutic Magnetic Resonance (TMR(r))
      improves the quality of granulation tissue.
AB  - Diabetic foot ulcers (DFUs) often result in severely adverse outcomes, such as
      serious infections, hospitalization, and lower extremity amputations. In last few
      years, to improve the outcome of DFUs, clinicians and researchers put their
      attention on the application of low intensity pulsating electro-magnetic fields
      through Therapeutic Magnetic Resonance (TMR(r)). In our study, patients with DFUs
      have been divided into two groups: The Sham Group treated with non-functioning
      TMR(r) device, and the Active Group treated with a functioning device. Biopsies
      were recovered from ulcers before and after a 15-day treatment with both kind of
      TMR(r) device. To recognize signs of inflammation or healing process, the
      harvested biopsies were subjected to histological and molecular analyses. The
      histological analysis showed a change in cell population after treatment with
      TMR(r): an increase of fibroblasts and endothelial cells with a reduction of
      inflammatory cells. After TMR(r) application, the gene expression profile
      analysis revealed an improvement in extracellular matrix components such as
      matrix metalloproteinases, collagens and integrins, a reduction in pro
      inflammatory interleukins, and an increase in growth factors expression. In
      conclusion, our research has identified histological and molecular features of
      reduced inflammation and increased cell proliferation during the wound healing
      process in response to TMR(r) application.

PMID- 29046050
TI  - Immunofluorescent characterization of non-myelinating Schwann cells and their
      interactions with immune cells in mouse mesenteric lymph node.
AB  - The central nervous system (CNS) influences the immune system in a general
      fashion by regulating the systemic concentration of humoral substances, whereas
      the autonomic nervous system communicates specifically with the immune system
      according to local interactions. Data concerning the mechanisms of this
      bidirectional crosstalk of the peripheral nervous system (PNS) and immune system
      remain limited. To gain a better understanding of local interactions of the PNS
      and immune system, we have used immunofluorescent staining of glial fibrillary
      acidic protein (GFAP), coupled with confocal microscopy, to investigate the non
      myelinating Schwann cell (NMSC)-immune cell interactions in mouse mesenteric
      lymph nodes. Our results demonstrate i) the presence of extensive NMSC processes
      and even of cell bodies in each compartment of the mouse mesenteric lymph node;
      ii) close associations/interactions of NMSC processes with blood vessels
      (including high endothelial venules) and the lymphatic vessel/sinus; iii) close
      contacts/associations of NMSC processes with various subsets of dendritic cells
      (such as CD4+CD11c+, CD8+CD11c+ dendritic cells), macrophages (F4/80+ and CD11b+
      macrophages), and lymphocytes. Our novel findings concerning the distribution of
      NMSCs and NMSC-immune cell interactions inside the mouse lymph node should help
      to elucidate the mechanisms through which the PNS affects cellular- and humoral
      mediated immune responses or vice versa in health and disease.

PMID- 29046051
TI  - Characterization of the skin mucus in the common octopus Octopus vulgaris
      (Cuvier) reared paralarvae.
AB  - The Octopus vulgaris farming is impaired by the high mortality of the paralarvae
      during the first month of life. Several factors have been investigated in this
      regard, but no data exist on the body surface mucus, which represents the
      interface with the outside environment. This study included morphometric analysis
      and glycoconjugates characterization of skin mucus in reared Octopus vulgaris
      paralarvae during the first month of life. Four types of mucous cells were
      distinguished:  mucous 1 (m1) and mucous 2 (m2) cells were scattered in the
      mantle epidermis, mucous 3 (m3) and mucous 4 (m4) in the epithelium surrounding
      the sucker. Except for the presence of fucosylated and neutral glycoconjugates in
      all mucous cells, each cell type expressed a characteristic glycopattern. m2 and
      m4 contained also suphate and acid non-sulphate glycans, m3 lacked suphate
      glycoproteins. Lectin histochemistry showed that mantle mucous cells (m1, m2)
      expressed GlcNAc and lactosamine terminating glycans. m2 also contained GalNAc
      terminal or penultimate to sialic acid. m3 was distinguished by mannosylated
      glycans terminating with lactosamine and m4 by alpha2,6 sialoglycans.
      Glycoproteins terminating with lactosamine, Galbeta1,3GalNAc, and alpha1,6-linked
      fucose were a common feature of paralarvae surface layer. Morphometry revealed a
      significant decrease of m1 and m2 abundance during the first month of life,
      afterwards the reared paralarvae died. Since the glycopattern did not change
      during the investigated period, the mantle mucous cells abundance could be
      related to the Octopus vulgaris paralarvae survival.

PMID- 29046052
TI  - Protective effect of different antioxidant agents in UVB-irradiated
      keratinocytes.
AB  - Skin cells can respond to UVB-induced damage either by tolerating it, or
      restoring it through antioxidant activation and DNA repair mechanisms or,
      ultimately, undergoing programmed cell death, when damage is massive. Nutritional
      factors, in particular, food antioxidants, have attracted much interest because
      of their potential use in new preventive, protective, and therapeutic strategies
      for chronic degenerative diseases, including skin inflammation and cancer. Some
      polyphenols, present in virgin olive oil, well tolerated by organism after oral
      administration, show a variety of pharmacological and clinical benefits such as
      anti-oxidant, anti-cancer, anti-inflammatory, and neuro-protective activities.
      Here, the protective effects of antioxidant compounds against UV-induced
      apoptosis have been described in HaCat cell line. Human keratinocytes were pre
      treated with antioxidants before UVB exposure and their effects have been
      evaluated by means of ultrastructural analyses. After UVB radiation, a known cell
      death trigger, typical apoptotic features, absent in control condition and in
      antioxidant alone-treated cells, appear. An evident numerical decrease of
      ultrastructural apoptotic patterns and TUNEL positive nuclei can be observed when
      natural antioxidants were supplied before cell death induction. These data have
      been confirmed by molecular investigation of caspase activity. In conclusion,
      this paper highlights antioxidant compound ability to prevent apoptotic cell
      death in human keratinocytes exposed to UVB, suggesting, for these molecules, a
      potential role in preventing skin damage.

PMID- 29046053
TI  - Ultrastructure and immunohistochemical characterization of proteins concerned
      with the secretory machinery in goat ceruminous glands.
AB  - The expression of soluble N-ethyl-maleimide sensitive fusion attachment protein
      receptor (SNARE) proteins in apocrine glands has not been fully elucidated. In
      addition to performing ultrastructural observation of the ceruminous glands in
      goats, our study focuses on the demonstration of beta-defensins, SNARE proteins
      and Rab3D in these glands with the use of immunohistochemical methods. The
      secretory cells were equipped with two types of vesicles, Golgi apparatus and
      abundant rough endoplasmic reticulum (ER). Additionally, in some of them, the
      characteristic concentric structures composed of rough ER were observed in their
      circum- and infranuclear parts. The expression of phosphorylated inositol
      requiring enzyme 1a was also detected. These findings may indicate their ability
      to produce numerous secretory proteins and the maintenance of homeostasis in the
      glandular cells. Furthermore, beta-defensins were demonstrated as products of the
      ceruminous glands. The present investigation also revealed the presence of SNARE
      proteins and Rab3D. It is suggested that these proteins are concerned with the
      secretory machinery of this gland type.

PMID- 29046054
TI  - Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal
      ligament stem cells: role of epigenetic modifications to the inflammation.
AB  - Periodontitis is a chronic oral inflammatory disease produced by bacteria.
      Gingival retraction and bone and connective tissues resorption are the hallmarks
      of this disease. Chronic periodontitis may contribute to the risk of onset or
      progression of neuroinflammatory pathological conditions, such as Alzheimer's
      disease. The main goal of the present study was to investigate if the role of
      epigenetic modulations is involved in periodontitis using human periodontal
      ligament stem cells (hPDLSCs) as an in vitro model system. hPDLSCs were treated
      with lipopolysaccharide of Porphyromonas gingivalis and the expression of
      proteins associated with DNA methylation and histone acetylation, such as DNMT1
      and p300, respectively, and inflammatory transcription factor NF-kB, were
      examined. Immunofluorescence, Western blot and next generation sequencing results
      demonstrated that P. gingivalis lipopolysaccharide significantly reduced DNA
      methylase DNMT1, while it markedly upregulated the level of histone
      acetyltransferase p300 and NF-kB in hPDLSCs. Our results showed that P.
      gingivalis lipopolysaccharide markedly regulate the genes involved in epigenetic
      mechanism, which may result in inflammation induction. We propose that P.
      gingivalis lipopolysaccharide-treated hPDLSCs could be a potential in vitro model
      system to study epigenetics modulations associated with periodontitis, which
      might be helpful to identify novel biomarkers linked to this oral inflammatory
      disease.

PMID- 29046055
TI  - Topographic distribution pattern of morphologically different G cells in the
      murine antral mucosa.
AB  - Gastrin-secreting enteroendocrine cells (G cells) in the antrum play an important
      role in the regulation of gastric secretion, gastric motility and mucosal cell
      proliferation. Recently we have uncovered the existence of two subpopulations of
      G cells with pivotally different morphology and a distinct localization in the
      antral invaginations; the functional implications of the different G cell types
      are still elusive. In this study a transgenic mouse line in which EGFP is
      expressed under the control of a gastrin promoter was used to elucidate the
      distribution pattern of the two G cell types throughout the different regions of
      the antrum. The results of immunohistochemical analyses revealed that G cells
      were not equally distributed along the anterior/posterior axis of the antrum. The
      "typical" pyramidal- or roundish-shaped G cells, which are located in the basal
      region of the antral invaginations, were more abundant in the proximal antrum
      bordering the corpus region but less frequent in the distal antrum bordering the
      pylorus. In contrast, the "atypical" G cells, which are located in the upper part
      of the antral invaginations and have a spindle-like contour with long processes,
      were evenly distributed along the anterior/posterior axis. This characteristic
      topographic segregation supports the notion that the two G cell types may serve
      different functions. A comparison of the antrum specific G cells with the two pan
      gastrointestinal enteroendocrine cell types, somatostatin-secreting D cells and
      serotonin-secreting enterochromaffin (EC) cells, revealed a rather similar
      distribution pattern of G and D cells, but a fundamentally different distribution
      of EC cells. These observations suggest that distinct mechanisms govern the
      spatial segregation of enteroendocrine cells in the antrum mucosa.

PMID- 29046056
TI  - Overview of the optical properties of fluorescent nanoparticles for optical
      imaging.
AB  - Nanoparticles (NPs) include a wide group of small structures composed by very
      different materials and characterized by peculiar properties that make them
      suitable for many applications, especially imaging and drug delivery. In this
      overview we focus on the optical properties of fluorescent NPs available for in
      vivo, in vitro and ex vivo preclinical studies and detectable with the optical
      imaging technique alone or in combination with microscopic confocal imaging. We
      summarize here the basic principles of the optical detection of fluorescent NPs,
      elucidate which are the current issues to be resolved and possible solutions to
      achieve the highest sensitivity and specificity for an unbiased analysis. So far
      NPs application in clinic is in evaluation due to safety questions still
      unaddressed but in the future they could dramatically improve both preclinical
      research and patient clinical care.

PMID- 29046058
TI  - Oocytes - Maternal Information and Functions.
AB  - This book presents different aspects of oocytes maturation in several animal
      models as the interactions oocyte-environment, the specific functions of oocytes
      molecules and organelles regulated by epigenetic and translational mechanisms and
      the evolution of maternal factors...

PMID- 29046057
TI  - Bile duct ligature in young rats: A revisited animal model for biliary atresia.
AB  - Biliary atresia leads to cirrhosis in the vast majority of patients and
      constitutes the first cause of paediatric liver transplantation. Animal models
      allow us to understand the molecular basis and natural history of diseases. The
      aim of this study is to describe a surgically created animal model of biliary
      atresia with emphasis in long-term liver function. Forty-two 3-week-old Sprague
      Dawley rats were randomly divided into two groups: bile duct ligature (BDL) and
      control. The animals were sacrificed on the 2nd, 4th, and 6th postoperative
      weeks. Blood samples were collected for liver function analysis. The spleen to
      body weight ratio was determined. Histopathological examination of liver tissue
      was performed by hematoxylin-eosin and Sirius red staining. Collagen
      quantification was determined by using colorimetric digital image analysis and
      was expressed as a percentage of total liver tissue area. Quantitative real-time
      polymerase chain reaction was performed to analyse gene expression levels of
      transforming growth factor-beta1 (Tgfb1) and apeline (Apln) genes. Statistical
      analysis was performed where P<0.05 was considered significant. Animals from BDL
      group developed increasing cholestasis with clinical and laboratory features.
      Splenomegaly was detected at 4th and 6th week (P<0.05). Histological evaluation
      of the liver showed ductular reaction, portal fibrosis and bile plugs. Collagen
      area to total liver tissue area had a median of 2.5% in the control group and 6.5
      %, 14.3 % and 37.7 % in BDL rats at 2nd, 4th and 6th weeks respectively
      (P<0.001). Tgfb1 mRNA expression level was significantly higher at 6th week
      (P<0.001) in BDL group when compared to control. Apln mRNA expression level was
      significantly higher at 4th and 6th week (P<0.001) and showed a positive linear
      correlation (r = 0.975, P<0.05) in BDL group when compared to control. Bile duct
      ligature in young rats is an animal model that recreates clinical, laboratory,
      histological and molecular findings of biliary atresia. Bile duct ligature
      constitutes a good animal model to investigate therapeutic approaches for
      modifying the progression of liver fibrosis in biliary atresia.

PMID- 29046059
TI  - Bis(dipyrrinato)zinc(II) Complex Chiroptical Wires: Exfoliation into Single
      Strands and Intensification of Circularly Polarized Luminescence.
AB  - One-dimensional (1D) coordination polymers (CPs) experiences limitations in
      exfoliation into individual strands, which hamper their utility as functional 1D
      nanomaterials. Here we synthesize chiral 1D-CPs that feature the
      bis(dipyrrinato)zinc(II) complex motif. They can be exfoliated into single
      strands upon sonication in organic media, retaining lengths of up to 3.19 MUm
      (ca. 2600 monomer units). Their chiroptical structure allows the exfoliated wires
      to show circularly polarized luminescence at an intensity 5.9 times that of
      reference monomer complexes.

PMID- 29046060
TI  - Crystalline Monomeric Allenyl/Propargyl Radical.
AB  - Reduction of alkynyl iminium salts derived from cyclic (alkyl)(amino)carbenes
      (CAACs) affords propargyl/allenyl radicals. Depending on the nature of the CAAC
      and alkyne substituents, these radicals can irreversibly dimerize, exist as
      monomers in solution but dimerize in the solid state, or can even remain
      monomeric as solids. The first characterization of an allenyl radical by single
      crystal X-ray crystallography is reported.

PMID- 29046061
TI  - Three-Dimensional Bacterial Behavior near Dynamic Surfaces Formed by Degradable
      Polymers.
AB  - Understanding the behavior of bacteria near biodegradable surfaces is critical
      for the development of biomedical and antibiofouling materials. By using digital
      holographic microscopy (DHM), we investigated the three-dimensional (3D) behavior
      of Escherichia coli and Pseudomonas sp. in lipase-containing aquatic environments
      near dynamic surfaces constructed by biodegradable poly(epsilon-caprolactone)
      (PCL)-based polymers in real time. As the enzymatic degradation rate increases,
      the percentage of near-surface subdiffusive bacteria and consequently, the
      irreversible adhesion decreases. Atomic force microscopy (AFM) measurements
      reveal that the adhesion force between bacteria and the surfaces decreases with
      an increasing degradation rate. In addition, the degradation products elicit a
      negative chemotactic response in E. coli, further driving them away from the
      dynamic surfaces through more frequent tumbling motion. Our study clearly
      demonstrates that bacterial adhesion can be reduced on dynamic surfaces formed by
      degradable polymers.

PMID- 29046062
TI  - Viewpoints on the 2017 American Conference on Theoretical Chemistry.

PMID- 29046063
TI  - Spotlights: Volume 8, Issue 20.

PMID- 29046064
TI  - Perspective Collections in the Limelight.

PMID- 29046066
TI  - Treatment options and reproductive outcome for adenomyosis-associated
      infertility.
AB  - PURPOSE: Adenomyosis is a benign gynecological disease mostly diagnosed in the
      forth and fifth decades. The recent improvement of the diagnostic tools and a
      better understanding of the pathology allowed clinicians to postulate a possible
      relationship between adenomyosis and infertility and to diagnose it in younger
      asymptomatic women during infertility work-up. Purpose of this article is to
      review the different theories regarding the possible correlation between
      adenomyosis and infertility and to discuss the treatment options and the final
      reproductive outcome after the treatment. MATERIALS AND METHODS: We search Pubmed
      for articles published in the English language with the use of the following MeSH
      search terms: "adenomyosis" combined with "treatment" and "fertility outcome"
      with the restriction to the human species. A manual search of review articles and
      cross-references completed the search. All selected articles were assessed for
      study design, patients characteristic, diagnosis of adenomyosis, type of
      treatment, post-treatment rates of conception, full-term pregnancy and
      completeness of information of the data sets. RESULTS: Limited data are available
      concerning the efficacy of the different treatment options of adenomyosis on
      fertility outcome and the only ones published are retrospective evaluations or
      small case series. CONCLUSIONS: Adenomyosis represents a common gynecological
      disorder with a negative impact on fertility. However, it remains challenging to
      establish if adenomyosis is the only cause of the infertility or not, because
      patients, in both case and control groups, may be affected by concomitant
      endometriosis. Further studies are required to determine the reason of
      implantation failure in women with adenomyosis and the impact of adenomyosis on
      infertile women with or without endometriosis.

PMID- 29046065
TI  - Investigational PD-1 inhibitors for advanced non-small lung cancer: new players
      in a shifting paradigm.

PMID- 29046068
TI  - Corrigendum.

PMID- 29046067
TI  - Making Food Aid Fit-for-Purpose in the 21st Century: A Review of Recent
      Initiatives Improving the Nutritional Quality of Foods Used in Emergency and
      Development Programming.
AB  - Important strides have been made recently in upgrading the global food aid agenda
      in line with evolving medical and nutrition sciences, operational experience, and
      innovations in food technology. A 2011 report endorsed by the United States
      Agency for International Development (USAID) recommended numerous improvements to
      products intended to support improved survival and nutrition in humanitarian
      programming, as well as greater rigor and transparency in the research agenda
      that supports innovations in this critical field. This article reviews progress
      since 2011 made by USAID, and other global food aid providers, in developing food
      aid products that are fit-for-purpose and are appropriately formulated to save
      lives in emergencies and to promote healthy mothers and children in nonemergency
      contexts. It highlights important modifications and addition made to products and
      identifies persisting knowledge gaps that should be prioritized in future
      research.

PMID- 29046069
TI  - Assuring children's human right to freedom of opinion and expression in
      education.
AB  - The Universal Declaration of Human Rights elaborated for children through the
      United Nations Convention on the Rights of the Child, mandates each child's right
      to participate in all matters affecting them. In particular, Article 19 includes
      the child's right to freedom of expression and opinion, access to information and
      communication choice. However, many barriers placed on children's daily lives
      often restrict or limit the enactment of children's participatory rights in
      practice, most noticeably in education. It is often the adult who decides what,
      when and how children can communicate, and the extent children's views and
      opinions are sought, considered or incorporated. This paper explores how
      children's daily lives are mediated in ways that restrict their expression, voice
      and communication rights. Children spend a significant proportion of their daily
      lives in education settings yet the restrictions on children's access to
      information and communication choices do not reflect contemporary pedagogical
      thinking. Many school settings perpetuate the key participation barriers of adult
      attitude and knowledge, pedagogical tradition, organisational structure and
      technological advancement. Such barriers to engagement stifle the realisation of
      the child's communication rights that then limits educational enhancement.
      Supporting children's right to communicate via a range of media enables pedagogy
      supporting voice-inclusive practice.

PMID- 29046070
TI  - Placenta previa without morbidly adherent placenta: comparison of characteristics
      and outcomes between planned and emergent deliveries in a tertiary center.
AB  - OBJECTIVE: The objective of this study is to compare patient outcomes between
      planned and emergent cesarean deliveries for placenta previa without morbidly
      adherent placenta. STUDY DESIGN: All patients with confirmed, persistent placenta
      previa (without morbidly adherent placentation) who underwent the surgery between
      January 2010 and April 2016 were included in this retrospective study. Primary
      outcome was composite maternal morbidity defined as the presence of at least one
      of the followings: death, red blood cell (RBC) transfusion, hysterectomy,
      reoperation, hospital stay >7 d, ureteral injury, bowel injury, or cystotomy.
      RESULTS: Three hundred and four patients with placenta previa were identified
      during the study period, of whom 154 (50.65%) had an antenatal and 10 (3.28%) had
      an intraoperative diagnosis of morbidly adherent placenta. One hundred and forty
      patients met the inclusion criteria. Eighty (57.1%) underwent planned cesarean
      delivery (planned cesarean delivery (PCD) group), and 60 (42.8%) required
      emergent cesarean delivery due to uterine contractions and/or bleeding (emergent
      cesarean delivery (ECD) group). Baseline characteristics were similar between the
      two groups except for the gestational age at delivery (36.0 weeks (36.0, 37.0) in
      PCD versus 34.0 weeks (32.0, 36.0) in ECP, p < .001). Composite maternal
      morbidity was not significantly different between two groups: 11 (18.3%) in ECD
      and 10 (12.5%) in PCD (p = .35) Conclusions: In our referral tertiary centre,
      emergent and planned cesarean deliveries for placenta previa without morbidly
      adherent placenta have similar maternal outcomes. In patients without significant
      hemorrhage, delivery may be safely deferred until 36-37 weeks.

PMID- 29046071
TI  - Clinical Significance of the Serotonin Release Assay and Platelet Count
      Monitoring After Cardiac Surgery.
AB  - Heparin-induced thrombocytopenia (HIT) is one of the serious complications in
      patients who undergo cardiac surgery. However, there remains a major problem in
      diagnosing HIT because the current immunological assays for detection of HIT
      antibody have limitations. Furthermore, the clinical course of thrombocytopenia
      in this surgery makes it increasingly difficult to diagnose HIT. We investigated
      the relationship between platelet count and HIT antibody in 59 patients who
      underwent cardiac surgery using cardiopulmonary bypass (CPB). The number of
      postoperative HIT antibody-positive patients evaluated using enzyme-linked
      immunosorbent assay kit (polyanion IgG/IgA/IgM complex antibodies/antiplatelet
      factor 4 enhanced) was 37 (62.7%). In contrast, platelet activation by HIT
      antibody was evaluated using the serotonin release assay (SRA). More than 20% and
      50% release of serotonin was obtained from 12 patients (20.3%) and 8 patients
      (13.6%), respectively. The levels of d-dimer were significantly different on
      postoperative day 14 between SRA-positive and SRA-negative groups; however,
      postoperative thrombus complication was not detected using sonography in the
      patients with positive serotonin release at all. After being decreased by the
      operation, their platelet count recovered within 2 weeks in both groups equally.
      In our study, although the patients were positive in the platelet activating HIT
      antibody assay, they remained free from thrombosis and their platelet count
      recovered after early postoperative platelet decrease. Therefore, in addition to
      the SRA, monitoring of platelet count might be still considered an indispensable
      factor to facilitate the prediction of HIT thrombosis prior to manifestation in
      the patients undergoing cardiac surgery using CPB.

PMID- 29046072
TI  - Commentary on the clinical and preclinical dosage limits of interstitially
      administered magnetic fluids for therapeutic hyperthermia based on current
      practice and efficacy models.
AB  - We offer a critique of what constitutes a suitable dosage limit, in both clinical
      and preclinical studies, for interstitially administered magnetic nanoparticles
      in order to enable therapeutic hyperthermia under the action of an externally
      applied alternating magnetic field. We approach this first from the perspective
      of the currently approved clinical dosages of magnetic nanoparticles in the
      fields of MRI contrast enhancement, sentinel node detection, iron replacement
      therapy and magnetic thermoablation. We compare this to a simple analytical model
      of the achievable hyperthermia temperature rise in both humans and animals based
      on the interstitially administered dose, the heating and dispersion
      characteristics of the injected fluid, and the strength and frequency of the
      applied magnetic field. We show that under appropriately chosen conditions a
      therapeutic temperature rise is achievable in clinically relevant situations. We
      also show that in such cases it may paradoxically be harder to achieve the same
      therapeutic temperature rise in a preclinical model. We comment on the
      implications for the evidence-based translation of hyperthermia based
      interventions from the laboratory to the clinic.

PMID- 29046073
TI  - Influence of farewell rituals and psychological vulnerability on grief following
      perinatal loss in monochorionic twin pregnancy.
AB  - AIM: The aim of this study is to analyze whether the absence of farewell rituals
      and previous psychological vulnerability are associated with the intensity of
      grief following perinatal loss in monochorionic twin pregnancy. METHOD: The
      sample comprised 28 women who experienced perinatal loss following fetal surgery.
      Sociodemographic and clinical data and information about farewell rituals were
      collected through interview. The women also completed a questionnaire about
      perinatal grief. RESULTS: A history of psychological and/or psychopharmacological
      treatment was associated with more intense grief following perinatal loss.
      CONCLUSION: Women with a history of psychological difficulties are particularly
      vulnerable to a complicated grief reaction after experiencing perinatal loss.
      However, the intensity of grief did not differ significantly according to whether
      or not the women performed some kind of farewell ritual. Further studies are
      needed to investigate these relationships and to encourage and facilitate the
      development of specific interventions for this population.

PMID- 29046074
TI  - Large cystic lympangioma of the pancreas: a case reportum.
AB  - Lymphangioma of the pancreas is rare and presents as a large cystic mass in the
      retroperitoneum. The pancreatic origin can be confirmed by careful evaluation of
      cross sectional imaging. Preoperative differentiation from other pancreatic
      cystic neoplasms is difficult but possible. Large symptomatic lesions warrant
      surgery. The diagnosis is confirmed by typical features on histopathology and
      immunohistochemistry. Presented here is a case report of a pancreatic
      lymphangioma, discussed in the context of available literature.

PMID- 29046075
TI  - Portal hypertension and chylous ascites complicating acute pancreatitis: the
      therapeutic value of portal vein stenting.
AB  - Chylous ascites as a consequence of acute pancreatitis is very rare. We present
      an unusual case of a 73-year-old man who developed refractory chylous ascites one
      month after an acute severe episode of gallstone pancreatitis, associated with
      portal hypertension. He was successfully treated with portal vein stenting, which
      has remained patent to date.

PMID- 29046076
TI  - The lesser spotted pregnant surgeon.
AB  - With more women entering surgical training, it will become more commonplace to
      encounter pregnant surgeons. This paper discusses the evidence for work-related
      risk factors as well as outlining the rights of a pregnant doctor. There are, in
      fact, very few real risks to pregnancy encountered as a surgeon, with the main
      risks involving standing or sitting for long periods and fatigue, which can be
      managed with support from the department. It is important for women in surgery to
      know that it is possible to continue their training while pregnant so they do not
      feel pressured into changing to a less demanding specialty or even leaving
      medicine entirely. It is also important for other professionals to understand the
      risks and choices faced by pregnant surgeons so that they can better support them
      in the workplace.

PMID- 29046077
TI  - Cost-effectiveness of routine imaging of suspected appendicitis.
AB  - Introduction The misdiagnosis of appendicitis and consequent removal of a normal
      appendix occurs in one in five patients in the UK. On the contrary, in healthcare
      systems with routine cross-sectional imaging of suspected appendicitis, the
      negative appendicectomy rate is around 5%. If we could reduce the rate in the UK
      to similar numbers, would this be cost effective? This study aimed to calculate
      the financial impact of negative appendicectomy at the Queen Alexandra Hospital
      and to explore whether a policy of routine imaging of such patients could reduce
      hospital costs. Materials and methods We performed a retrospective analysis of
      all appendicectomies over a 1-year period at our institution. Data were extracted
      on outcomes including appendix histology, operative time and length of stay to
      calculate the negative appendicectomy rate and to analyse costs. Results A total
      of 531 patients over 5 years of age had an appendicectomy. The negative
      appendicectomy rate was 22% (115/531). The additional financial costs of negative
      appendicectomy to the hospital during this period were L270,861. Universal
      imaging of all patients with right iliac fossa pain that could result in a 5%
      negative appendicectomy rate would cost between L67,200 and L165,600 per year but
      could save L33,896 (magnetic resonance imaging), L105,896 (computed tomography)
      or L132,296 (ultrasound) depending on imaging modality used. Conclusions Negative
      appendicectomy is still too frequent and results in additional financial burden
      to the health service. Routine imaging of patients with suspected appendicitis
      would not only reduce the negative appendicectomy rate but could lead to cost
      savings and a better service for our patients.

PMID- 29046078
TI  - Blood on screwdriver tip to aid screw insertion at depth.

PMID- 29046079
TI  - Iliac crest apophyseal insufficiency avulsion fractures.
AB  - Iliac crest apophyseal avulsion fractures are rare injuries caused mainly through
      forceful contraction of attached muscles during high level sporting activities.
      We present the first case of a spontaneous iliac crest apophyseal avulsion
      insufficiency fracture in a patient with severe atopic eczema on oral steroids
      and review the relevant literature.

PMID- 29046080
TI  - The use of viable cryopreserved placental tissue in the management of a chronic
      rectovaginal fistula.
AB  - We present a case of a chronic recurrent rectovaginal fistula that initially
      arose from complications of haemorrhoid surgery and had failed multiple prior
      surgical repairs. The fistula was successfully managed using viable cryopreserved
      placental tissue.

PMID- 29046081
TI  - Splenic artery pseudoaneurysm causing delayed gastrointestinal bleeding after
      gastrocolonic fistula following sleeve gastrectomy.
AB  - Delayed gastrointestinal bleeding in the context of a gastric fistula is a very
      rare complication of longitudinal sleeve gastrectomy. We report the case of a
      patient who presented with massive gastrointestinal bleeding from a
      pseudoaneurysm arising from the splenic artery following complications after a
      longitudinal sleeve gastrectomy several months previously. The case was
      successfully managed with angiographic embolisation and we present our experience
      with recommendations for managing this rare but life-threatening complication.

PMID- 29046082
TI  - Hydronephrotic kidney with multiple extra-renal calyces.
AB  - Extra-renal calyces are a rare anomaly of the renal collecting system,
      characterised by the presence of calyces and pelvis outside the renal parenchyma.
      It may also be associated with other anomalies, such as renal ectopia, fusion and
      malrotation. We describe an unusual case of extra-renal calyces with six long
      calyces arising from a suspected multicystic dysplastic kidney that was
      successfully managed laparoscopically.

PMID- 29046083
TI  - Variable life adjusted display methodology for continuous performance monitoring
      of carotid endarterectomy.
AB  - Introduction The aim of this study was to use variable life-adjusted display
      (VLAD) methodology to monitor performance of six vascular surgeons undertaking
      carotid endarterectomy in a single institution. Materials and methods This was a
      prospective study with continuous analysis. A risk score model to predict 30-day
      stroke or death for individual patients was developed from data collected from
      839 patients from 1992 to 1999. The model was used to monitor performance of six
      surgeons from 2000 to 2009. Individual risk factors and 30-day outcomes were
      analysed and VLAD plots were created for the whole unit and for each surgeon.
      Results Among the 941 carotid endarterectomies in the performance analysis, 28
      adverse events were recorded, giving an overall stroke or death rate of 3.06%.
      The risk model predicted there would be 33 adverse events. There was no
      statistical difference between the predicted and the observed adverse events (P >
      0.2, chi2 value 1.25, 4 degrees of freedom). The VLAD plot for the whole unit
      shows an overall net gain in operative performance, although this could have been
      chance variation. The individual VLAD plot showed that surgeons 1, 2, 3 and 6 to
      have an overall net gain in the number of successful operations. The changes
      observed between the surgeons was not significant (P > 0.05) suggesting chance
      variation only. Conclusions Performance of carotid endarterectomy can be
      continuously assessed using VLAD methodology for units and individual surgeons.
      Early identification and correction of performance variation could facilitate
      improved quality of care.

PMID- 29046084
TI  - Penetrating neck injuries: a guide to evaluation and management.
AB  - Introduction Penetrating neck injury is a relatively uncommon trauma presentation
      with the potential for significant morbidity and possible mortality. There are no
      international consensus guidelines on penetrating neck injury management and
      published reviews tend to focus on traditional zonal approaches. Recent
      improvements in imaging modalities have altered the way in which penetrating neck
      injuries are now best approached with a more conservative stance. A literature
      review was completed to provide clinicians with a current practice guideline for
      evaluation and management of penetrating neck injuries. Methods A comprehensive
      MEDLINE (PubMed) literature search was conducted using the search terms
      'penetrating neck injury', 'penetrating neck trauma', 'management', 'guidelines'
      and approach. All articles in English were considered. Articles with only limited
      relevance to the review were subsequently discarded. All other articles which had
      clear relevance concerning the epidemiology, clinical features and surgical
      management of penetrating neck injuries were included. Results After initial
      resuscitation with Advanced Trauma Life Support principles, penetrating neck
      injury management depends on whether the patient is stable or unstable on
      clinical evaluation. Patients whose condition is unstable should undergo
      immediate operative exploration. Patients whose condition is stable who lack hard
      signs should undergo multidetector helical computed tomography with angiography
      for evaluation of the injury, regardless of the zone of injury. Conclusions The
      'no zonal approach' to penetrating neck trauma is a selective approach with
      superior patient outcomes in comparison with traditional management principles.
      We present an evidence-based, algorithmic and practical guide for clinicians to
      use when assessing and managing penetrating neck injury.

PMID- 29046085
TI  - Transoral laser surgery for laryngeal carcinoma: has Steiner achieved a genuine
      paradigm shift in oncological surgery?
AB  - Transoral laser microsurgery applies to the piecemeal removal of malignant
      tumours of the upper aerodigestive tract using the CO2 laser under the operating
      microscope. This method of surgery is being increasingly popularised as a single
      modality treatment of choice in early laryngeal cancers (T1 and T2) and
      occasionally in the more advanced forms of the disease (T3 and T4), predominantly
      within the supraglottis. Thomas Kuhn, the American physicist turned philosopher
      and historian of science, coined the phrase 'paradigm shift' in his
      groundbreaking book The Structure of Scientific Revolutions. He argued that the
      arrival of the new and often incompatible idea forms the core of a new paradigm,
      the birth of an entirely new way of thinking. This article discusses whether
      Steiner and colleagues truly brought about a paradigm shift in oncological
      surgery. By rejecting the principle of en block resection and by replacing it
      with the belief that not only is it oncologically safe to cut through the
      substance of the tumour but in doing so one can actually achieve better results,
      Steiner was able to truly revolutionise the management of laryngeal cancer. Even
      though within this article the repercussions of his insight are limited to the
      upper aerodigestive tract oncological surgery, his willingness to question other
      peoples' dogma makes his contribution truly a genuine paradigm shift.

PMID- 29046086
TI  - The provision of surgical tracheostomies by maxillofacial surgeons in the UK:
      time for a dedicated tracheostomy team?
AB  - Surgical tracheostomy is a commonly provided service by surgical teams for
      patients in intensive care where percutaneous dilatational tracheostomy is
      contraindicated. A number of factors may interfere with its provision on shared
      emergency operating lists, potentially prolonging the stay in intensive care. We
      undertook a two-part project to examine the factors that might delay provision of
      surgical tracheostomy in the intensive care unit. The first part was a
      prospective audit of practice within the University Hospital Coventry. This was
      followed by a telephone survey of oral and maxillofacial surgery units throughout
      the UK. In the intensive care unit at University Hospital Coventry, of 39
      referrals, 21 (53.8%) were delayed beyond 24 hours. There was a mean (standard
      deviation) time to delay of 2.2 days (0.9 days) and the most common cause of
      delay was surgeon decision, accounting for 13 (61.9%) delays. From a telephone
      survey of 140 units nationwide, 40 (28.4%) were regularly involved in the
      provision of surgical tracheostomies for intensive care and 17 (42.5%)
      experienced delays beyond 24 hours, owing to a combination of theatre
      availability (76.5%) and surgeon availability (47.1%). There is case for having a
      dedicated tracheostomy team and provisional theatre slot to optimise patient
      outcomes and reduce delays. We aim to implement such a move within our unit and
      audit the outcomes prospectively following this change.

PMID- 29046087
TI  - Fine wire frame foot plate positioning.

PMID- 29046088
TI  - Perineal colostomy prolapse: a novel application of mesh sacral pexy.
AB  - Full thickness colonic prolapse following pseudocontinent perineal colostomy has
      not been previously reported. Possible contributing factors include a large skin
      aperture at the site of the perineal stoma, the absence of anal sphincters and
      mesorectal attachments and the presence of a perineal hernia. A novel application
      of sacral pexy combined with perineal hernia repair using two prosthetic meshes
      is described.

PMID- 29046089
TI  - The hidden cost of deep neck space infections
AB  - Introduction The incidence of deep neck space infection (DNSI) is rising and
      appears to be related to falling rates of tonsillectomy. The purpose of this
      study was to assess demographics of patients presenting with DNSI and the
      financial burden to the National Health Service (NHS). Methods Data were
      collected retrospectively on patients aged over 16 years admitted to NHS Greater
      Glasgow and Clyde with DNSI between 2012 and 2016. Demographics, aetiology and
      use of hospital resources were reviewed. The cost of hospital admissions was
      calculated using data from NHS Scotland's Information Services Division, the
      local diagnostics division and the British National Formulary. Results Seventy
      four patients were admitted with DNSI during the study period. Forty (54%) were
      male. The mean age was 44.0 years (range: 16-86 years). The most frequent source
      of infection was the tonsil (n=30, 40.5%). The most common infective organism was
      Streptococcus constellatus (n=9, 12.2%). The mean length of stay was 11 days.
      Fifty-five patients (74.3%) required operative intervention. The mean cost of
      admission per patient was L5,700 (range: L332-L46,700). Conclusions This study
      highlights the high cost burden of DNSI to the NHS. The incidence of DNSI in
      Glasgow has risen over the study period; contributing factors may include the
      reduced tonsillectomy rate and a reduction in antibiotic prescribing. As the
      incidence of DNSI continues to rise, there will be an increase in cost to the
      NHS, which must be planned for.

PMID- 29046090
TI  - Is the number of new trauma and orthopaedic consultant posts increasing or
      decreasing?
AB  - Introduction Trauma and orthopaedics is a popular surgical specialty in the UK.
      Recent changes to the National Health Service have suggested an imbalance with
      fewer jobs yet more trainees. Furthermore, subspecialisation is emerging within
      all surgical disciplines. The aim of this study was to examine whether there were
      decreasing numbers of trauma and orthopaedic (T&O) consultant appointments in the
      UK, and to determine the frequency of subspecialisation. Methods All 51 issues of
      the British Medical Journal (BMJ) careers supplement from the year 2000 were
      reviewed as well as the 51 issues from 2010. The number of T&O posts, requested
      subspecialty interests and the number of posts in other surgical specialties were
      analysed. Results A total of 481 consultant posts in T&O were advertised in the
      102 issues of the careers supplements reviewed. Of these, 281 were advertised in
      2000 and 200 in 2010. The mean number of posts per issue was 5.5 in 2000 and 3.9
      in 2010. In 2000 orthopaedic posts represented 30.5% of all surgical posts while
      in 2010 this was 37.8%. Under two-thirds (61.6%) of posts requested a specialty
      interest in 2000 but this increased to 93% in 2010. The greatest increase in
      named subspecialty was seen in 'spine' (from 4.1% to 19.0%.) while 'general' had
      the greatest decrease (from 38.4% to 7.0%). Conclusions UK consultant posts in
      T&O are decreasing in frequency. Most advertised posts request a subspecialty
      interest but registrar training focuses on producing 'generally' competent
      orthopaedic consultants. The onus is therefore on fellowships to develop
      subspecialty interest. As these are not all educationally approved,
      reconfiguration of fellowships is likely to be necessary.

PMID- 29046091
TI  - Crossing the bridge to VATS lobectomy.
AB  - Introduction The impact of the introduction of video assisted thoracoscopic
      surgery (VATS) on the management of lung cancer 20 years ago has been well
      documented. However, the uptake of VATS lobectomy in surgical practice worldwide
      has been slower than expected. We believe that this is partly due to a lack of
      consensus on how this procedure should be integrated into training programmes. We
      present our initial experience with a newly developed training model, which could
      help bridge the divide between open and VATS lobectomy. Methods Two surgical
      registrars were initiated into this model, supervised by a single consultant. All
      cases were performed using a standardised three-port anterior approach with
      systematic lymph node dissection. Both registrars were scrubbed for each case,
      alternating as first surgeon and assistant, with the supervising consultant
      operating the camera. Results Over a 6-month period, 22 lung resections for non
      small cell lung carcinoma were performed as VATS lobectomies. Thirteen of them
      were upper lobectomies. There were no emergency conversions to open surgery. The
      mean operative time for the registrars was 155 minutes compared with 140 minutes
      for consultant-led operations (p=0.22). There was no perioperative mortality. The
      most common postoperative complications were atrial fibrillation (4 cases) and
      prolonged air leak (3 cases). Conclusions VATS lobectomy involves a team
      approach. Especially in upper lobectomies, the assistant surgeon plays a
      significant role in the operation, often helping with the dissection as well as
      stapling of the bronchial and vascular structures. With a team consisting of two
      trainees and a supervising surgeon, the teaching process becomes more intuitive
      and is accelerated. This should reduce the learning curve considerably and
      improve safety during training.

PMID- 29046092
TI  - Informed consent and the readability of the written consent form.
AB  - Introduction The aim of this study was to objectively ascertain the level of
      readability of standardised consent forms for orthopaedic procedures. Methods
      Standardised consent forms (both in summary and detailed formats) endorsed by the
      British Orthopaedic Association (BOA) were retrieved from orthoconsent.com and
      assessed for readability. This involved using an online tool to calculate the
      validated Flesch reading ease score (FRES). This was compared with the FRES for
      the National Health Service (NHS) Consent Form 1. Data were analysed and
      interpreted according to the FRES grading table. Results The FRES for Consent
      Form 1 was 55.6, relating to the literacy expected of an A level student. The
      mean FRES for the BOA summary consent forms (n=27) was 63.6 (95% confidence
      interval [CI]: 61.2-66.0) while for the detailed consent forms (n=32), it was
      68.9 (95% CI: 67.7-70.0). All BOA detailed forms scored >60, correlating to the
      literacy expected of a 13-15-year-old. The detailed forms had a higher FRES than
      the summary forms (p<0.001). Conclusions This study demonstrates that the BOA
      endorsed standardised consent forms are much easier to read and understand than
      the NHS Consent Form 1, with the detailed BOA forms being the easiest to read.
      Despite this, owing to varying literacy levels, a significant proportion of
      patients may struggle to give informed consent based on the written information
      provided to them.

PMID- 29046093
TI  - Video-assisted anal fistula treatment: a high volume unit initial experience.
AB  - Introduction Perianal fistulas are a common problem. Video-assisted anal fistula
      treatment is a new technique for the management of this difficult condition. We
      describe our initial experience with the technique to facilitate the treatment of
      established perianal fistulas. Methods We reviewed a prospectively maintained
      database relating to consecutive patients undergoing video-assisted anal fistula
      treatment in a single unit. Results Seventy-eight consecutive patients had their
      perianal fistulas treated with video-assistance from November 2014 to June 2016.
      Complete follow-up data were available in 74 patients, with median follow-up of
      14 months (interquartile range 7-19 months). There were no complications and all
      patients were treated as day cases. Most patients had recurrent disease, with 57
      (77%) having had previous fistula surgery. At follow-up, 60 (81%) patients
      reported themselves 'cured' (asymptomatic) including 5 patients with Crohn's
      disease and one who had undergone 10 previous surgical procedures. Logistical
      stepwise regression did not demonstrate any statistically significant factors
      that may have been considered to affect outcome (age, gender, diabetes, previous
      I&D, Crohn's disease, smoking, type of fistula). Conclusions Our data have shown
      that video-assisted anal fistula treatment is safe and effective in the
      management of perianal fistulas in our patients and this suggests it may be
      applied to all patients regardless of comorbidity, underlying pathology or type
      of fistula.

PMID- 29046094
TI  - Ostomy creation with fewer sutures using tissue adhesives (cyanoacrylates) in
      inflammatory bowel disease: a pilot study.
AB  - Introduction Fistula formation around the ostomy site is a stoma-related
      complication often requiring surgical intervention. This complication may be
      caused by sutures or may develop as a complication of inflammatory bowel disease.
      Before conducting a clinical trial, we set out to investigate the safety of
      ostomy creation with fewer sutures using tissue adhesives in this pilot study.
      Methods Patients with inflammatory bowel disease who required surgery with ostomy
      creation at the Hyogo College of Medicine between January 2014 and December 2015
      were enrolled. Safety was assessed by evaluating the incidence of stoma-related
      complications. Ostomy was restricted to loop ileostomy and was created with two
      sutures and tissue adhesives. Results A total of 14 patients were enrolled. Mean
      body mass index was 18.9 +/- 2.0 kg/m2. There were no cases of ostomy retraction
      and no severe adverse events were observed. Conclusions This pilot study
      demonstrates that ostomy creation using tissue adhesives is safe. Although
      retraction and adverse events were not observed, even in patients with
      inflammatory bowel disease who generally exhibit delayed wound healing, the body
      mass index was extremely low in this series. This study does not strongly
      recommend ostomy creation with tissue adhesives; further studies are needed to
      clarify the efficacy and safety of the procedure.

PMID- 29046095
TI  - Surgical placement of rectus sheath catheters in a cadaveric cystectomy model.
AB  - Introduction Surgically inserted rectus sheath catheters (RSCs) are used
      increasingly for analgesia after cystectomy and other abdominal surgery.
      Currently, there is little information on the optimal positioning of RSCs to
      allow maximal spread of local anaesthetic. This study sought to assess the spread
      of dye injected via RSCs and to highlight the extent of its coverage in a fresh
      unembalmed cadaveric cystectomy model in order to confirm the nerve endings that
      are likely to be anaesthetised with RSCs. Methods Four cadavers underwent lower
      midline incision with limited bladder mobilisation. A RSC was inserted into the
      eight hemiabdomens. The RSCs were positioned either anterior (n=5) or posterior
      to the rectus muscle (n=3). Dye was injected down the RSCs to evaluate spread.
      The eight hemiabdomens were dissected anatomically to determine the surface area
      of dye spread and nerve root involvement. Results The mean surface area of dye
      spread with anteriorly placed RSCs was 30.6cm2 anterior and 25.9cm2 posterior to
      the rectus muscle. The mean surface area of dye spread with posteriorly placed
      RSCs was 11.3cm2 anterior and 37.3cm2 posterior to the rectus muscle. The mean
      number of nerve roots stained with anteriorly and posteriorly placed RSCs was 3.8
      and 2.7 respectively. Subcutaneous spread of dye was seen with one anterior RSC
      insertion. Peritoneal spread was seen with one anteriorly positioned RSC.
      Conclusions This study has demonstrated efficient nerve root infiltration with
      anteriorly and posteriorly positioned RSCs. It appears that dye spreads between
      the fibres of the rectus muscle rather than out laterally to the nerve roots when
      spreading from its initial compartment.

PMID- 29046096
TI  - Demonstrating local flaps - A simple model as part of informed consent.

PMID- 29046097
TI  - A novel cabling technique.

PMID- 29046098
TI  - Infection of PTFE mesh 15 years following pedicled TRAM flap breast
      reconstruction: mechanism and aetiology.
AB  - The pedicled transverse rectus abdominis myocutaneous (TRAM) flap procedure is
      still widely used for breast reconstruction. The repair of the flap harvest site
      in the transverse rectus abdominis muscle and sheath is often assisted by the use
      of prosthetic meshes. This decreases the risk of abdominal wall weakness and
      herniation but, being a foreign body, it also carries the risk of infection. In
      this report, we describe the case of a 63-year-old patient who, whilst receiving
      chemotherapy for metastatic breast cancer, presented with an infected
      polytetrafluoroethylene mesh 15 years after pedicled TRAM flap immediate breast
      reconstruction. This necessitated mesh removal to treat the infection. Following
      a thorough review of the English literature, this is the longest recorded
      presentation of an abdominal prosthetic mesh infection. The mechanism and
      aetiology of such a late complication are discussed.

PMID- 29046099
TI  - Neuroendocrine tumours within a Meckel's diverticulum.
AB  - A Meckel's diverticulum is a common anomaly of the gastrointestinal tract.
      Although the majority of patients do not have any symptoms, malignancies can
      develop inside these diverticula, with neuroendocrine tumours being the most
      common. Diverticulectomy is the best option for complicated diverticula but
      prophylactic resection of asymptomatic diverticula in adults remains
      controversial. We present a case series of three patients with a neuroendocrine
      tumour found in a Meckel's diverticulum. Given the number of asymptomatic
      diverticula not resected, it seems likely that incidental neuroendocrine tumours
      are more prevalent than thought previously. With the minimally invasive
      techniques now available and the low complication rate for incidental
      diverticulectomy, we believe that the benefits of resection of this high risk
      area for cancer outweigh the risks of surgery.

PMID- 29046100
TI  - Analysis of intensive care admissions among paediatric obstructive sleep apnoea
      referrals.
AB  - Introduction The aim of this study was to identify the proportion of children
      referred to a paediatric tertiary referral centre who required admission to the
      paediatric intensive care unit (PICU) following surgery for obstructive sleep
      apnoea (OSA) and to establish risk factors for these admissions. Methods
      Retrospective review of case notes and the operative database was performed for
      all children undergoing adenotonsillectomy for sleep disordered breathing and OSA
      symptoms in Great Ormond Street Hospital over a 10-year period. Results Overall,
      1,328 children underwent adenotonsillectomy for sleep disordered breathing and
      OSA. The mean age was 3.1 years (standard deviation [SD]: 1.7 years). A total of
      37 (2.8%) were admitted to the PICU postoperatively (mean length of PICU stay:
      1.2 days, standard deviation [SD]: 0.6 days) and 282 (21.2%) required
      nasopharyngeal airway (nasal prong) insertion intraoperatively. The mean length
      of stay on the ward following surgery was 1.4 days (SD: 0.8 days). Patients with
      severe OSA (apnoea-hypopnoea index [AHI] >10) and ASA (American Society of
      Anesthesiologists) grade >=3 were more likely to require postoperative PICU
      admission (22/37 vs 381/1,291 [p<0.001] and 29/37 vs 660/1,291 [p=0.001]
      respectively). Severe OSA was also more common in children who required nasal
      prong insertion intraoperatively (186/282 vs 217/1,046, p<0.001). Conclusions
      Very few children referred to a paediatric tertiary referral centre actually
      require PICU admission following surgery. This may be in part due to the use of a
      nasopharyngeal airway in patients where postoperative obstruction is anticipated.
      In children with severe OSA (AHI >10) and an ASA grade of >=3, nasopharyngeal
      airway insertion and potential admission to the PICU should be considered.

PMID- 29046101
TI  - Anorectal melanoma: experience from a tertiary cancer care centre in South India.
AB  - Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive
      disease, in which early diagnosis is difficult. The prognosis remains extremely
      poor, irrespective of the treatment. We share our experience in treating this
      malignancy at our centre in South India. Methods This study describes a
      retrospective analysis of 31 cases of anorectal melanoma presented to our centre
      between January 2001 and December 2013. Results Twenty-two patients (71%)
      presented with metastasis and had a median overall survival of nine months. None
      of the 22 patients survived for two years. Nine patients (29%) had curative
      surgery, in the form of abdominoperineal resection (six patients),
      abdominoperineal resection with bilateral inguinal node dissection (one patient),
      abdominoperineal resection with liver resection (one patient) and posterior
      exenteration (one patient). In patients who underwent curative surgery, the
      median overall survival was 15 months and disease-free survival was nine months,
      with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an
      aggressive disease with a poor prognosis. The majority of patients present with
      distant metastases. Prognosis depends on stage at presentation. Early diagnosis
      and surgical resection may improve the overall outcome. Newer modalities such as
      immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and
      anti-programmed cell death protein 1 monoclonal antibodies have radically changed
      the management of mucosal melanoma and may, in the future, improve the overall
      prognosis of anorectal melanoma.

PMID- 29046102
TI  - Hip fracture surgery in mixed-use emergency theatres: is the infection risk
      increased? A retrospective matched cohort study.
AB  - Introduction The National Institute of Health and Care Excellence recommends that
      people with hip fracture should have surgery on the day of, or the day after,
      admission. However, there remains unacceptable variation in performance around
      the country, with a range of 13-91% of patients meeting this target. Dedicated
      trauma lists have insufficient capacity in many hospitals. We occasionally employ
      a mixed-use emergency theatre to facilitate early surgery. Increased risk of
      infection has been raised as a concern owing to microbial surface contamination
      from a preceding unclean case and lack of laminar flow in these theatres. The
      objective of this study was to investigate whether there is an increased risk of
      surgical site infections in patients who had hip fracture surgery in a mixed-use
      emergency theatre. Methods Between August 2010 and July 2014, 74 patients had hip
      fracture surgery in a mixed-use emergency theatre without laminar flow. This
      group was compared with a control group of patients who had hip fracture surgery
      in dedicated orthopaedic theatres with laminar flow. Infection was the primary
      outcome measured. Results There was no statistically significant difference in
      the rate of infection, length of stay or 30-day mortality, readmission or
      reoperation rates between the two groups. Conclusions Operating on hip fractures
      in mixed-use theatre did not lead to an increase in infection or other
      complications in our series. We feel that the risk of infection can be balanced
      against advantages of timely operation and it may therefore be justified to use
      these theatres when faced with lack of time on the trauma list. A much larger
      series would be required to investigate the effects of confounders.

PMID- 29046103
TI  - Smartphone flashlight to aid in locating lost and dropped surgical sharps.

PMID- 29046104
TI  - How the Child's Gender Matters for Families Having a Child With Congenital
      Adrenal Hyperplasia.
AB  - Children with congenital adrenal hyperplasia (CAH) are exposed to high levels of
      testosterone in utero often resulting in nontypical genitalia at birth for girls.
      The purpose of this analysis, which draws on data from a larger study, was to
      examine, based on the gender of the child, the family experiences of having a
      child with CAH. Sixteen parents were interviewed, and comparisons were made
      across all categories coded in the parents' interviews to examine similarities
      and differences in the experiences of families based on the child's gender.
      Families having a daughter with CAH experienced additional challenges when
      compared with families having a son. These include fear of stigmatization,
      challenging surgical decisions, and concerns regarding disclosure of the
      condition. Acknowledging this and creating support programs tailored for girls
      that address surgical procedures and complications resulting from being born with
      elevated testosterone are critical to promoting a healthy family and child
      response.

PMID- 29046105
TI  - Safety and patients' satisfaction after hysteroscopic sterilisation.
AB  - The aim of this study was to understand the potential complications of the
      Essure(r) device as well as the factors influencing its onset and patient
      satisfaction. We present a 9-year descriptive prospective study that included
      1068 patients. The device was placed in 1056 of them (98.8%); 894 had no pain or
      mild pain during the insertion and only 12 patients experienced pain greater than
      menstrual pain. The proportion of patients without pain was greater in the group
      that took NSAIDs or NSAIDs and BZD and the unmedicated group had the highest rate
      of severe pain (p = .00). In all, 161 of the 1064 patients who had the Essure(r)
      inserted reported having an adverse effect during the 3-months post-insertion
      (pelvic pain or discomfort). The mean score out of 10 attributed to this method
      was 9.06 (S = 1.11). We concluded that the Essure(r) shows a low rate of
      complications and users showed a high degree of satisfaction. Impact statement
      What is already known on this subject: There are few international publications
      on Essure(r). When we conducted a search in PubMed for the term 'Essure', we
      obtained 221 publications. When we added the terms 'Essure and complications', we
      obtained 20 publications, and when we increased the restriction including
      'satisfaction', we obtained seven; thus, the uniqueness of our study. What the
      results of this study add: We present a 9-year descriptive prospective study that
      included 1068 patients. The aim of this study was to understand the potential
      complications of the Essure(r) device (Bayer, Whippany, NJ), as well as factors
      that can influence its onset and the patient satisfaction. The device was placed
      in 1056 of the patients (98.8%); 894 had no pain or mild pain during the
      insertion and only 12 patients experienced pain greater than menstrual pain. The
      proportion of patients without pain was greater in the group that took NSAIDs or
      NSAIDs and BZD and the unmedicated group had the highest rate of severe pain
      (p=.00). What the implications are of these findings for clinical practice and/or
      further research: Our study shows a low rate of complications with Essure(r),
      mild and transient in most cases, as well as a high degree satisfaction.
      Nevertheless, given the few published studies on this device, we believe that
      long-term follow-up is needed.

PMID- 29046106
TI  - Expression of von Willebrand factor and caldesmon in the placental tissues of
      pregnancies complicated with intrauterine growth restriction.
AB  - PURPOSE: The decreased placental perfusion is the underlying reason for
      intrauterine growth restriction that in turn leads to reduced placental perfusion
      and ischemia. However, there are several issues to be understood in the
      pathophysiology of intrauterine growth restriction. We aimed to study whether any
      compensatory response in placental vascular bed occur in pregnancies complicated
      with intrauterine growth restriction by the immunohistochemical staining of von
      Willebrand factor and caldesmon in placental tissues. MATERIALS AND METHODS: A
      total of 103 pregnant women was enrolled in the study including 50 patients who
      were complicated with IUGR and 50 uncomplicated control patients. The study was
      designed in a prospective manner. All placentas were also stained with von
      Willebrand factor and caldesmon monoclonal kits. RESULTS: The immunohistochemical
      staining of von Willebrand factor and caldesmon expressions in placental tissues
      were different between normal and intrauterine growth restriction group. The
      percentages of 2+ and 3+ von Willebrand factor expression were higher in the
      intrauterine growth restriction group comparing with the normal group, although
      the difference was not statistically significant. The intensity of caldesmon
      expression was significantly lower in the intrauterine growth restriction group
      in comparison with the normal group (p < .001). CONCLUSION: Angiogenesis occurs
      as a placental response to intrauterine growth restriction which is a hypoxic
      condition. But newly formed vessels are immature and not strong enough. Our study
      is important to clarify the pathophysiology and placental compensatory responses
      in intrauterine growth restriction.

PMID- 29046107
TI  - Determinants of Endotracheal Intubation in Critically Ill Patients Undergoing
      Gastrointestinal Endoscopy Under Conscious Sedation.
AB  - OBJECTIVES: Our primary aim was to determine the factors leading to prophylactic
      endotracheal intubation in intensive care unit (ICU) patients undergoing
      gastrointestinal endoscopy. Secondary aims were to determine the rate of
      unplanned endotracheal intubations during endoscopy and to determine the rate of
      aspiration following endoscopy for patients admitted to the ICU. METHODS:
      Critically ill adult (>=18 years) patients who underwent upper and lower
      endoscopic procedures from January 2012 to July 2016 in a medical/surgical ICU
      were included. Determinants of prophylactic endotracheal intubation prior to
      endoscopy as well as other postprocedure outcomes were electronically captured by
      a validated data mart system. Given our focus on aspiration in those who were not
      endotracheally intubated prior to endoscopy, we used a validated definition a
      priori. RESULTS: A total of 320 patients were included in the final analysis:
      76(24%) were intubated prior to endoscopy and 244 (76%) were not. The
      endotracheally intubated group had a significantly higher Acute Physiologic and
      Chronic Health Evaluation III (44.5 [16.2] vs 39.5 [15.5]; P = .02) and
      Sequential Organ Failure Assessment (6.9 [4.4] vs 3.8 [3]; P <= .01) scores,
      higher rate of hematemesis within 24 hours of endoscopy (28 [37%] vs 45 [18%]; P
      <= .01), and higher rate of upper endoscopy (72 [96%] vs 181 [74%]; P <= .01). We
      composed a composite outcome for multivariable analyses, which demonstrated the
      rate of any complication was significantly higher among those who were intubated
      prior to the procedure versus those who were not intubated previously (odds
      ratio: 2.80, 95% confidence interval (CI): 1.16-6.72, P = .02). CONCLUSION:
      Endoscopy performed in the ICU without endotracheal intubation is safe. However,
      patient selection for prophylactic intubation prior to endoscopy is of critical
      importance as illustrated in this study with higher illness severity, planned
      upper endoscopy, and hematemesis 24 hours prior being key factors on deciding to
      perform endotracheal intubation. Prophylactic intubation for endoscopy and
      preexisting cardiac disease were associated with a higher rate of adverse
      outcomes.

PMID- 29046108
TI  - Prenatal diagnosis of truncus arteriosus in the first trimester with a high
      frequency curved transducer.

PMID- 29046109
TI  - Use of the profunda artery perforator flap in vulvo-perineal reconstruction.

PMID- 29046110
TI  - Image Sharpness and Contrast Tuning in the Early Visual Pathway.
AB  - The center-surround organization of the receptive fields (RFs) of retinal
      ganglion cells highlights the presence of local contrast in visual stimuli. As RF
      of thalamic relay cells follow the same basic functional organization, it is
      often assumed that they contribute very little to alter the retinal output.
      However, in many species, thalamic relay cells largely outnumber their retinal
      inputs, which diverge to contact simultaneously several units at thalamic level.
      This gain in cell population as well as retinothalamic convergence opens the door
      to question how information about contrast is transformed at the thalamic stage.
      Here, we address this question using a realistic dynamic model of the
      retinothalamic circuit. Our results show that different components of the
      thalamic RF might implement filters that are analogous to two types of well-known
      image processing techniques to preserve the quality of a higher resolution
      version of the image on its way to the primary visual cortex.

PMID- 29046111
TI  - EEG Classification with a Sequential Decision-Making Method in Motor Imagery BCI.
AB  - To develop subject-specific classifier to recognize mental states fast and
      reliably is an important issue in brain-computer interfaces (BCI), particularly
      in practical real-time applications such as wheelchair or neuroprosthetic
      control. In this paper, a sequential decision-making strategy is explored in
      conjunction with an optimal wavelet analysis for EEG classification. The subject
      specific wavelet parameters based on a grid-search method were first developed to
      determine evidence accumulative curve for the sequential classifier. Then we
      proposed a new method to set the two constrained thresholds in the sequential
      probability ratio test (SPRT) based on the cumulative curve and a desired
      expected stopping time. As a result, it balanced the decision time of each class,
      and we term it balanced threshold SPRT (BTSPRT). The properties of the method
      were illustrated on 14 subjects' recordings from offline and online tests.
      Results showed the average maximum accuracy of the proposed method to be 83.4%
      and the average decision time of 2.77[Formula: see text]s, when compared with
      79.2% accuracy and a decision time of 3.01[Formula: see text]s for the sequential
      Bayesian (SB) method. The BTSPRT method not only improves the classification
      accuracy and decision speed comparing with the other nonsequential or SB methods,
      but also provides an explicit relationship between stopping time, thresholds and
      error, which is important for balancing the speed-accuracy tradeoff. These
      results suggest that BTSPRT would be useful in explicitly adjusting the tradeoff
      between rapid decision-making and error-free device control.

PMID- 29046112
TI  - A comparison of positive vicarious learning and verbal information for reducing
      vicariously learned fear.
AB  - Research with children has demonstrated that both positive vicarious learning
      (modelling) and positive verbal information can reduce children's acquired fear
      responses for a particular stimulus. However, this fear reduction appears to be
      more effective when the intervention pathway matches the initial fear learning
      pathway. That is, positive verbal information is a more effective intervention
      than positive modelling when fear is originally acquired via negative verbal
      information. Research has yet to explore whether fear reduction pathways are also
      important for fears acquired via vicarious learning. To test this, an experiment
      compared the effectiveness of positive verbal information and positive vicarious
      learning interventions for reducing vicariously acquired fears in children (7-9
      years). Both vicarious and informational fear reduction interventions were found
      to be equally effective at reducing vicariously acquired fears, suggesting that
      acquisition and intervention pathways do not need to match for successful fear
      reduction. This has significant implications for parents and those working with
      children because it suggests that providing children with positive information or
      positive vicarious learning immediately after a negative modelling event may
      prevent more serious fears developing.

PMID- 29046113
TI  - Association between plasma retinol binding protein 4 levels and severe
      preeclampsia.

PMID- 29046114
TI  - Pregnancy in 3M syndrome.

PMID- 29046116
TI  - Impact of human milk banking on neonatal mortality, necrotizing enterocolitis,
      and exclusive breastfeeding - experience from a tertiary care teaching hospital,
      south India.
AB  - OBJECTIVE: The objective of this study is to study the impact of a Human Milk
      Bank (HMB) on neonatal mortality, incidence of necrotizing enterocolitis (NEC)
      and rate of exclusive breastfeeding. METHODS: This pre-post intervention study
      was conducted in a tertiary care teaching institute in south India. Data
      regarding neonatal mortality, incidence of NEC, and exclusive breastfeeding rates
      were collected for a period of 6 months before and after establishing a modern
      HMB and compared. RESULTS: The number of deliveries, live births, and incidence
      of preterm and VLBW neonates during pre- and post-HMB periods were comparable.
      Neonatal mortality was 11.32/1000 live births pre-HMB compared with 10.77/1000
      live births post HMB. The incidence of NEC was 1.26% of live births pre-HMB
      compared with 1.07% post-HMB. Exclusive breastfeeding rate pre-HMB was 34%
      compared with 74% post HMB (p < .001). CONCLUSION: There is a decreasing trend in
      neonatal mortality and incidence of NEC after establishing a HMB. Human milk
      banking significantly improved exclusive breastfeeding rate in the population
      studied.

PMID- 29046117
TI  - Where Is "Family" in the Social Determinants of Health? Implications for Family
      Nursing Practice, Research, Education, and Policy.

PMID- 29046115
TI  - Bone and the Immune System.
AB  - Osteoporosis increases fracture risk, a cause of crippling morbidity and
      mortality. The immunoskeletal interface (ISI) is a centralization of cell and
      cytokine effectors shared between skeletal and immune systems. Consequently, the
      immune system mediates powerful effects on bone turnover. Physiologically, B
      cells secrete osteoprotegerin (OPG), a potent anti-osteoclastogenic factor that
      preserves bone mass. However, activated T cells and B cells secrete pro
      osteoclastogenic factors including receptor activator of Nuclear factor-kappaB
      (NF-kB) ligand (RANKL), Interleukin (IL)-17A, and tumor necrosis factor (TNF)
      alpha promoting bone loss in inflammatory states such as rheumatoid arthritis.
      Recently, ISI disruption has been linked to osteoporosis in human
      immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS),
      where elevated B cell RANKL and diminished OPG drive bone resorption. HIV
      antiretroviral therapy paradoxically intensifies bone loss during disease
      reversal, as immune reconstitution produces osteoclastogenic cytokines.
      Interestingly, in estrogen deficiency, activated T cells secrete RANKL, TNF, and
      IL-17A that amplify bone resorption and contribute to postmenopausal
      osteoporosis. T cell-produced TNF and IL-17A further contribute to bone loss in
      hyperparathyroidism, while T cell production of the anabolic Wingless integration
      site (Wnt) ligand, Wnt10b, promotes bone formation in response to anabolic
      parathyroid hormone and the immunomodulatory costimulation inhibitor cytotoxic T
      lymphocyte-associated protein-4-IgG (abatacept). These findings provide a window
      into the workings of the ISI and suggest novel targets for future therapeutic
      interventions to reduce fracture risk.

PMID- 29046118
TI  - A theoretical approach for a weighted assessment of the mutagenic potential of
      nanomaterials.
AB  - Several approaches have recently been proposed for predicting the potential
      hazard and risk to human health of engineered nanomaterials (NMs). Here, we
      present a theoretical approach to assess the mutagenic potential of NMs, which
      could be incorporated into risk assessment tools. Following the weight of
      evidence approach recommended for chemicals, we describe criteria for evaluating
      and weighting existing literature information, based on current knowledge on the
      relevance and limitations of genotoxicity and mutagenicity assays used in testing
      NMs. The relevant assays are then categorized according to the genotoxic events
      detected in three categories: DNA damage, gene mutations and chromosomal damage -
      the former weighing lower than the two latter ones, since unrepairable
      alterations have more weight than those depicting primary DNA damage that can
      still be repaired. Besides, evidence from in vivo tests are given a higher weight
      than data coming from in vitro tests, because animal studies can more accurately
      predict secondary genotoxicity. Although studies conducted according to validated
      protocols have greater weight, studies that do not comply with conventional test
      guidelines are also considered, trying to make use of all available information
      for each NM. A threshold of agreement among studies belonging to the same
      category is required to consider this category positive or negative for
      mutagenicity. The final outcome is a statement on the mutagenic potential of the
      nanoform and the uncertainty of this evaluation. Finally, we discuss new methods
      and possible improvements in current assays that could be incorporated in future
      guidelines.

PMID- 29046119
TI  - Walking Children Through a Minefield: How Professionals Experience Exploring
      Adverse Childhood Experiences.
AB  - Understanding the challenges of professionals in addressing child adversity is
      key to improving the detection, protection, and care of exposed children. We
      aimed to synthesize findings from qualitative studies of professionals' lived
      experience of addressing child adversity. Through a systematic search, we
      identified eight qualitative studies and synthesized them using metaethnography.
      We generated three themes, "feeling inadequate," "fear of making it worse," and
      "facing evil," and one overarching metaphor, "walking children through a
      minefield." The professionals felt that they lacked the means necessary to
      explore child adversity, that they were apprehensive of worsening the child's
      situation, and that their work with child adversity induced emotional discomfort.
      This metasynthesis indicated that the professionals' efficiency in exploring
      abuse relied upon their ability to manage emotional and moral distress and
      complexity. To support children at risk, we propose developing professionals'
      ability to build relationships, skills in emotion regulation, and proficiency in
      reflective practice.

PMID- 29046120
TI  - Aflatoxins and ochratoxin A in flour: a survey of the Serbian retail market.
AB  - This report presents data on the occurrence of aflatoxins (AF) and ochratoxin A
      in different types of flour marketed in Serbia. A total of 114 samples of wheat,
      buckwheat, rye, oat, barley, rice, millet and corn flour were collected in the
      period 2012-2016 and analysed using high performance liquid chromatography with
      fluorescence detection. Among flours other than corn, AFB1 was quantified only in
      rice, while ochratoxin A (OTA) was found in 29% of the samples. In corn flours
      the percentage of positive samples varied greatly over the years: AFB1 7.1-80.0%,
      OTA 30.0-40.6%, with a co-occurrence of 7.1-34.4%. Overall 5.2% of flours other
      than corn and 10.7% of corn flours exceeded the maximum levels (MLs) for AFB1
      and/or OTA. The highest recorded levels were 8.80 MUg kg-1 of AFB1 (corn) and
      23.04 MUg kg-1 of OTA (rye). Overall mean contamination levels of corn flours
      were 0.53 MUg kg-1 of AFB1 and 0.46 MUg kg-1 of OTA.

PMID- 29046121
TI  - Cefepime Intravenous Push Versus Intravenous Piggyback on Time to Administration
      of First-Dose Vancomycin in the Emergency Department.
AB  - STUDY OBJECTIVE: The combination of cefepime and vancomycin is commonly used as
      an empiric antimicrobial regimen. Time to first-dose antibiotics is associated
      with survival benefit. The objective of this study is to evaluate whether
      cefepime intravenous push (IVP) is associated with a shorter time to vancomycin
      administration in the emergency department (ED) compared with cefepime
      intravenous piggyback (IVPB) infusion. METHODS: This was a retrospective chart
      review of records of patients who were treated with the vancomycin-cefepime
      combination in the ED. RESULTS: A total of 1071 charts from April 2013 to January
      2015 were reviewed. Included in the pre-(IVBP) group was 536 subjects and 535
      subjects in the post-(IVP) group. The indications for antibiotic therapy were
      sepsis alone (28.3%), pneumonia alone (30.7%), sepsis with pneumonia (36.5%), and
      other (4.6%). The median time from administration of cefepime to vancomycin were
      63.5 minutes and 2.0 minutes in the IVPB and IVP cohorts, respectively ( P <
      .001). CONCLUSION: The use of first-dose cefepime IVP in the ED resulted in a
      statistically significant decrease in time to vancomycin administration of over 1
      hour.

PMID- 29046122
TI  - The effect of hyoscine butylbromide on the duration and progress of labor in
      primigravidae: a randomized controlled trial: methodological issues.

PMID- 29046124
TI  - The 'full-blown' MRI of sudden hearing loss: 3D FLAIR in a patient with bilateral
      metastases in the internal auditory canals.
AB  - We report a case of a 57-year-old man with bilateral masses in the internal
      auditory canal. The peculiar findings at magnetic resonance imaging with
      tridimensional fluid-attenuated inversion recovery sequence combined with
      clinical data provided new insights into understanding the pathophysiology of the
      hearing loss.

PMID- 29046125
TI  - Pretreatment with N-acetyl cysteine suppresses chronic reactive astrogliosis
      following maternal nanoparticle exposure during gestational period.
AB  - Early pregnant employees are potentially and unintendedly exposed to industrial
      chemicals including nanoparticles. Developmental toxicity of nanoparticle
      exposure has been concerned because exposure to fine particle including carbon
      black nanoparticle (CB-NP) during the brain developmental stage enhances the risk
      of brain disorders. Maternal CB-NP exposure dose-dependently induces
      astrogliosis, which is an abnormal increase in the reactive astrocytes with glial
      fibrillary acidic protein (GFAP) and aquaporin-4 overexpression due to the
      destruction of nearby neurons and blood vessels. The present study aimed to
      investigate protective effects of antioxidants on the histopathological
      denaturation with astrogliosis following maternal CB-NP exposure in offspring
      mice, thereby to evaluate the role of oxidative stress on the developmental
      toxicity. Pregnant ICR mice were treated with CB-NP by intranasal instillation on
      gestational days 5 and 9. N-acetyl cysteine (NAC) or ascorbic acid was
      intraperitoneally administered to the pregnant mice 1 h prior to CB-NP
      instillation. The brains were collected from 6- to 12-week-old offspring mice and
      analyzed using western blotting and immunohistochemistry. NAC suppressed GFAP
      overexpression in 6- and 12-week-old offspring mice following maternal CB-NP
      exposure. However, NAC did not suppress aquaporin-4 overexpression following
      maternal CB-NP exposure. Ascorbic acid did not suppress, but rather slightly and
      significantly enhanced the expression of GFAP and aquaporin-4. These results
      indicate that astrogliosis by maternal CB-NP exposure is partially prevented by
      NAC pretreatment. Oxidative stress is a possible key factor of developmental
      neurotoxicity of maternal NP exposure. This study will contribute to elucidating
      the mechanisms underlying the effects of developmental neurotoxicity of NPs.

PMID- 29046123
TI  - Differential effects of silver nanoparticles on DNA damage and DNA repair gene
      expression in Ogg1-deficient and wild type mice.
AB  - Due to extensive use in consumer goods, it is important to understand the
      genotoxicity of silver nanoparticles (AgNPs) and identify susceptible
      populations. 8-Oxoguanine DNA glycosylase 1 (OGG1) excises 8-oxo-7,8-dihydro-2
      deoxyguanine (8-oxoG), a pro-mutagenic lesion induced by oxidative stress. To
      understand whether defects in OGG1 is a possible genetic factor increasing an
      individual's susceptibly to AgNPs, we determined DNA damage, genome
      rearrangements, and expression of DNA repair genes in Ogg1-deficient and wild
      type mice exposed orally to 4 mg/kg of citrate-coated AgNPs over a period of 7 d.
      DNA damage was examined at 3 and 7 d of exposure and 7 and 14 d post-exposure.
      AgNPs induced 8-oxoG, double strand breaks (DSBs), chromosomal damage, and DNA
      deletions in both genotypes. However, 8-oxoG was induced earlier in Ogg1
      deficient mice and 8-oxoG levels were higher after 7-d treatment and persisted
      longer after exposure termination. AgNPs downregulated DNA glycosylases Ogg1,
      Neil1, and Neil2 in wild type mice, but upregulated Myh, Neil1, and Neil2
      glycosylases in Ogg1-deficient mice. Neil1 and Neil2 can repair 8-oxoG. Thus,
      AgNP-mediated downregulation of DNA glycosylases in wild type mice may contribute
      to genotoxicity, while upregulation thereof in Ogg1-deficient mice could serve as
      an adaptive response to AgNP-induced DNA damage. However, our data show that Ogg1
      is indispensable for the efficient repair of AgNP-induced damage. In summary,
      citrate-coated AgNPs are genotoxic in both genotypes and Ogg1 deficiency
      exacerbates the effect. These data suggest that humans with genetic polymorphisms
      and mutations in OGG1 may have increased susceptibility to AgNP-mediated DNA
      damage.

PMID- 29046126
TI  - Co-occurrence of ochratoxin A and citrinin in unprocessed cereals established
      during a three-year investigation period.
AB  - The aim of this study was to investigate ochratoxin A (OTA) and citrinin (CIT) co
      occurrence in different unprocessed cereals (n = 189) originating from Croatia
      during a three-year investigation period (2014-2016) using validated enzyme
      immunoassay (ELISA) methods. CIT and OTA were determined in 49% and 7% of
      samples, respectively. Significantly higher (p < 0.05) overall mean
      concentrations were determined for CIT (66.8 +/- 76.0 ug/kg) in comparison to OTA
      (5.2 +/- 1.1 ug/kg). Based on the analysis of all investigated cereals, CIT was
      found about 15 times more frequently than OTA and in similarly (15-fold) higher
      concentrations, irrespective of the cultivation year. The results revealed a
      moderately positive correlation between OTA and CIT concentrations in maize (rs =
      0.44) and wheat (rs = 0.59), whereas in barley and oat this correlation (p >
      0.01) was not significant.

PMID- 29046128
TI  - Journal of Correctional Health Care.

PMID- 29046127
TI  - Serum ferritin is a different predictor from transfusion history for allogeneic
      transplantation outcome in patients with severe aplastic anemia.
AB  - OBJECTIVES: Severe aplastic anemia (SAA) patients receive more red blood cell
      (RBC) transfusions as supportive management. We aim to clarify the associations
      between transfusion history or pre-transplantation serum ferritin (SF) and the
      overall survival of allogeneic hematopoietic stem cell transplantation (allo
      HSCT) among SAA patients. MATERIAL AND METHODS: We retrospectively investigated
      96 SAA patients undergoing allo-HSCT, and grouped them according to pre
      transplantation duration. Pre-transplantation SF, transfused units and other iron
      related parameters were collected. Comparisons in transplantation outcomes and
      complications were made in groups with different SF levels and different
      transfusion histories. RESULTS: Among the 96 SAA patients, 45 patients received
      transplantation within 2 months after diagnosis (short-term pre-transplantation
      period), and the rest of the patients had long-term pre-transplantation
      treatment. Among the patients with short-term pre-transplantation treatment, a
      higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF
      also predicted a trend in incidence of higher bloodstream infection (p = 0.108).
      Significant correlations were observed between pre-transplantation SF and
      infection incidence, as well as transfusion history. However, for patients with
      longer pre-transplantation duration, transfusion history was associated with
      worse outcome (p = 0.026), in terms of higher incidence of acute graft versus
      host disease (p = 0.048). High SF was only significantly associated with
      prolonged RBC transfusion dependence post-transplantation (p = 0.044). DISCUSSION
      AND CONCLUSIONS: Transfusion history was a stronger predictor of outcome than SF
      in patients undergoing transplantation more than 2 months after diagnosis.

PMID- 29046129
TI  - Preventing Suicide in Forensic Settings: Assessment and Intervention for Inmates
      With Serious Mental Illness.
AB  - Suicide is one of the leading causes of inmate deaths in correctional settings.
      Furthermore, there is heightened risk for suicide among individuals diagnosed
      with serious mental illness (SMI) who present in jails and prisons. In the
      present article, the authors review suicide risk factors associated with SMI,
      with emphasis on incarcerated individuals, and discuss the best practices in
      assessing risk for suicide. The authors review interventions designed to prevent
      suicide among individuals with SMI in forensic settings. The article also points
      to the need for continued research to inform the development of assessment tools
      and intervention strategies for this population.

PMID- 29046130
TI  - Aflatoxin B1 and sterigmatocystin in wheat and wheat products from supermarkets
      in China.
AB  - Wheat is an important cereal but it is often contaminated with mycotoxins. The
      natural occurrence of aflatoxin B1 (AFB1) and sterigmatocystin (STC) was
      determined in 178 food samples (32 wheat samples and 146 wheat products)
      purchased from Chinese supermarkets. The methodology was validated, the wheat and
      wheat products samples were treated with a modified QuEChERS (quick, easy, cheap,
      effective, rugged, and safe) and quantified by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). From these samples 18.8% of wheat and 8.2% of cracker
      samples were contaminated with AFB1. Mean levels were 0.06 ug/kg and 0.05ug/kg,
      respectively. There was no AFB1 contamination in white bread or whole meal bread.
      Meanwhile 53.1% of wheat, 59.2% of crackers, 20.8% of white bread and 16% of
      whole meal bread samples were contaminated with STC. The mean levels were 0.07,
      0.79, 0.12 and 0.12 ug/kg respectively. Although the levels were low, this
      demonstrates the need for more comprehensive surveys for these two mycotoxins in
      wheat and wheat products from China.

PMID- 29046131
TI  - Understanding critical care nurses' autonomy in Jordan.
AB  - Purpose The aim of this study was to describe Jordanian critical care nurses'
      experiences of autonomy in their clinical practice. Design/methodology/approach A
      descriptive correlational design was applied using a self-reported cross
      sectional survey. A total of 110 registered nurses who met the eligibility
      criteria participated in this study. The data were collected by a structured
      questionnaire. Findings A majority of critical care nurses were autonomous in
      their decision-making and participation in decisions to take action in their
      clinical settings. Also, they were independent to develop their own knowledge.
      The study identified that their autonomy in action and acquired knowledge were
      influenced by a number of factors such as gender and area of practice. Practical
      implications Nurse's autonomy could be increased if nurses are made aware of the
      current level of autonomy and explore new ways to increase empowerment. This
      could be offered through classroom lectures that concentrate on the concept of
      autonomy and its implication in practice. Nurses should demonstrate autonomous
      nursing care at the same time in the clinical practice. This could be done
      through collaboration between educators and clinical practice to help merge
      theory to practice. Originality/value Critical care nurses were more autonomous
      in action and knowledge base. This may negatively affect the quality of patient
      care and nurses' job satisfaction. Therefore, improving nurses' clinical decision
      making autonomy could be done by the support of both hospital administrators and
      nurses themselves.

PMID- 29046133
TI  - Erratum.
AB  - Anderson R, Mueller R, Reese S, Wehner A. Evaluation of an automated enzyme
      linked fluorescent assay for thyroxine measurement in cat and dog sera. J Vet
      Diagn Invest 2017;29:278-286. (Original doi: 10.1177/1040638717696442).

PMID- 29046132
TI  - Maternal breastfeeding and autism spectrum disorder in children: A systematic
      review and meta-analysis.
AB  - OBJECTIVES: Autism spectrum disorder (ASD) refers to a group of conditions
      variably affecting communicative and social interactive abilities presenting
      alongside behaviors with various restricted and repetitive patterns. In addition
      to genetic factors that influence the onset of the symptoms, there is growing
      interest in the potential involvement of non-genetic environmental factors. Some
      aspects of breastfeeding practices, including rates, timing, or optimality, have
      been put forward as environmental risk factors for autism. However, previous
      studies showed a controversial relationship between ASD and breastfeeding.
      METHODS: A meta-analysis on the association between maternal breastfeeding and
      ASD in children was conducted. We also explored potential moderating factors
      which might influence this association. Articles reporting the association
      between breastfeeding and a diagnosis of ASD were included. RESULTS: Seven
      articles were included in the meta-analysis. Cumulatively, children with ASD (n =
      1463), either in the form of clinical diagnosis or self-report, were
      significantly less likely to have been breastfed than children without ASD (n =
      1180) (OR = 0.61, 95% CI = 0.45-0.83, P = 0.002). Subgroup analyses revealed that
      results remained significant for children who were breastfed with additional
      supplementation. DISCUSSION: This meta-analysis provides evidence that
      breastfeeding (exclusively or including additional supplements) may protect
      against ASD. Prospective longitudinal research is required to disentangle the
      complex relationships and to explore potential pathophysiological mechanisms.

PMID- 29046135
TI  - Correspondence Letter to the Editor Regarding "Anesthetic-Related Neurotoxicity
      and Neuroimaging in Children: A Call for Conversation" by Bjur, Payne, Nemergut,
      et al.

PMID- 29046136
TI  - Phenotype Development in Adolescents With Tourette Syndrome: A Large Clinical
      Longitudinal Study.
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by frequent
      comorbidities and a wide spectrum of phenotype presentations. This study aimed to
      describe the development of phenotypes in TS and tic-related impairment in a
      large longitudinal study of 226 children and adolescents followed up after 6
      years. The participants were clinically examined to assess tic severity and
      impairment, obsessive compulsive disorder (OCD), and attention
      deficit/hyperactivity disorder (ADHD). The development in phenotypes changed
      toward less comorbidity with 40% TS-only (no OCD or ADHD) (TS without OCD or
      ADHD) at baseline and 55% at follow-up.Tic-related impairment was expected to
      improve with an age-related tic decline, but surprisingly the impairment score
      did not reflect the tic decline. Sex, vocal and motor tics, and OCD and ADHD
      severity were highly significantly correlated to the impairment score. Knowledge
      of TS phenotype development is used in clinical settings to guide patients and
      for genetic, etiological, and clinical research purposes.

PMID- 29046137
TI  - Magnetic Resonance Imaging (MRI) and Digital Subtraction Angiography
      Investigation of Childhood Moyamoya Disease.
AB  - Because digital subtraction angiography (DSA) is not an ideal angiographic
      examination for moyamoya disease in the pediatric population, magnetic resonance
      angiography (MRA) provides a noninvasive contrast-free angiographic examination;
      whereas magnetic resonance imaging (MRI) provides superior spatial resolution and
      soft-tissue contrast for lesion assessment. Ninety patients with moyamoya disease
      were examined by MRI and DSA to assess the distribution of lesions and their
      diagnostic agreement between modalities. MRI examination revealed 439 lesions.
      Punctate lesions were the most abundant, followed by patchy lesions. These
      lesions generally covered a smaller area than the abnormal-vascular corresponding
      brain parenchyma. Steno-occlusive changes at bilateral anterior, medial, and
      posterior cerebral arteries were identified by MRA and DSA. MRI showed moderate
      agreement in identifying lesions after steno-occlusive changes in anterior and
      medial cerebral arteries, and good agreement in posterior cerebral arteries; 6%
      to 11% of cases were misdiagnosed by MRA.

PMID- 29046138
TI  - Usefulness of Simultaneous Measurement of Plasma Steroids, Including Precursors,
      for the Evaluation of Drug Effects on Adrenal Steroidogenesis in Rats.
AB  - The aim of this study was to evaluate the usefulness of simultaneous measurement
      of plasma steroids, including precursors, for the evaluation of drug effects on
      adrenal steroidogenesis in vivo. Plasma concentrations of corticosterone and its
      precursors were examined in rats dosed with compounds that affect adrenal
      steroidogenesis via different modes of action as well as the relationships of the
      changes with blood chemistry and adrenal histopathology. Male rats were dosed
      with tricresyl phosphate, aminoglutethimide, trilostane (TRL), metyrapone (MET),
      ketoconazole (KET), or mifepristone for 7 days. In the TRL, MET, and KET groups,
      precursor levels were markedly increased, while there were no significant changes
      in the corticosterone level, suggesting that the precursors are more sensitive
      biomarkers to detect the effect on adrenal steroidogenesis. Also, the precursors
      with increased levels were those that are normally metabolized by the inhibited
      enzymes, reflecting the modes of action of the compounds. In addition, different
      patterns of changes were observed in blood chemistry and histopathology,
      supporting the mechanism suggested by the steroid changes. These results show
      that simultaneous measurement of plasma steroids, including precursors, can be a
      valuable method to sensitively evaluate drug effects on adrenal steroidogenesis
      and to investigate the underlying mechanisms.

PMID- 29046139
TI  - Immunohistochemical Characterization of Sarcomas in Trp53+/- Haploinsufficient
      Mice.
AB  - The use of immunohistochemical (IHC) staining in determining and/or confirming
      the cellular origin of poorly differentiated sarcomas was evaluated in this
      study. Sarcomatous neoplasms were evaluated in a research study conducted in 2
      strains of p53+/- haploinsufficient mice. The most common neoplasms were
      undifferentiated sarcomas, followed by osteosarcomas and rhabdomyosarcomas
      (RMSs). The RMSs were poorly differentiated and appeared similar to the
      pleomorphic, or adult type, RMS of humans. All sarcomas stained positive by IHC
      for the mesenchymal cell intermediate filament vimentin. The RMSs were identified
      by positive IHC staining for myogenin, a transcription factor specific to
      skeletal muscle. Osteosarcomas were easily identifiable on hematoxylin and eosin
      stained slides; no generally accepted IHC stain specific for bone is presently
      available. Some of the undifferentiated sarcomas contained numerous macrophages
      that stained positive for F4/80, a macrophage marker; the positive-staining cells
      were considered to be infiltrating macrophages. One-third of the neoplasms
      observed in this study were associated with subcutaneous implanted electronic
      microchips used for animal identification. Based upon histopathologic evaluation
      and IHC staining, it was not possible to distinguish neoplasms associated with
      subcutaneous microchips from neoplasms not associated with microchips.

PMID- 29046141
TI  - Generation and Characterization of a Bispecific Antibody Targeting Both PD-1 and
      c-MET.
AB  - BACKGROUND: Bispecific antibodies, BsAbs, are molecules with the ability to bind
      to two different epitopes on the same or different antigens. c-MET, cellular
      mesenchymal to epithelial transition factor, is deregulated in many types of
      human malignancies. Abnormal c-MET activation in cancer correlates with poor
      prognosis. PD-1, programmed death-1, is an additional inhibitory receptor
      expressed by T cells. Blocking the interactions between PD-1 and PD-L1 has
      emerged as a promising immunotherapy for treating cancer. OBJECTIVES: The goal of
      this study was to identify a novel bispecific antibody targeting both c-MET and
      PD-1 as an anti-cancer therapeutic candidate. METHODS: The BsAb was produced
      using 293E expression system and purified by Protein A affinity chromatography.
      Then the binding specificity and affinity of the BsAb was examined by FACS and
      biolayer light interferometry. The ability of the BsAb to inhibit the
      proliferation of tuman cells was measured using the CellTiter 96 Aqueous One
      Solution Cell Proliferation Assay kit; the potential signaling pathway involved
      was identified by Western Blot. Cytokine secreted by PHA-L stimulated PBMC was
      measured by ELISA. Effects of BsAb on PBMC-mediated lysis of MKN45 cells was
      measured by LDH cytotoxicity assay. RESULTS: Based on the original sequences of
      PD-1 and c-MET mAb, a BsAb gene was designed, cloned into pCEP4 vector for
      expression in 293E cells. The BsAb was obtained after purification of the cell
      culture supernatant. It can bind to PD-1 and c-MET simultaneously, the calculated
      affinity was 11.5 nM for PD-1 and 9.09 nM for c-MET. The BsAb enhanced IFN-gamma
      production over control IgG by 2-3 folds. It also inhibit the c-MET pathway
      activation and the proliferation of tumor cells significantly, comparable to JnJ
      38877605. The BsAb showed dose-dependent cytotoxic activity against MKN45 cells.
      CONCLUSION: Our results indicated that a novel BsAb recognizing PD-1 and c-MET
      was successfully generated. It could redirect T cells to kill tumor cells, while
      retaining its inherent ability to restore T cells and inhibit tumor cells. With
      this potential, this BsAb could be developed as a therapeutic candidate for the
      treatment of various solid tumors.

PMID- 29046140
TI  - Amplification of arsenic genotoxicity by TiO2 nanoparticles in mammalian cells:
      new insights from physicochemical interactions and mitochondria.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) have shown great adsorption capacity
      for arsenic (As); however, the potential impact of TiO2 NPs on the behavior and
      toxic responses of As remains largely unexplored. In the present study, we
      focused on the physicochemical interaction between TiO2 NPs and As(III) to
      clarify the underlying mechanisms involved in their synergistic genotoxic effect
      on mammalian cells. Our data showed that As(III) mainly interacted with TiO2 NPs
      by competitively occupying the sites of hydroxyl groups on the surface of TiO2 NP
      aggregates, resulting in more aggregation of TiO2 NPs. Although TiO2 NPs at
      concentrations used here had no cytotoxic or genotoxic effects on cells, they
      efficiently increased the genotoxicity of As(III) in human-hamster hybrid (AL)
      cells. The synergistic genotoxicity of TiO2 NPs and As(III) was partially
      inhibited by various endocytosis pathway inhibitors while it was completely
      blocked by an As(III)-specific chelator. Using a mitochondrial membrane potential
      fluorescence probe, a reactive oxygen species (ROS) probe together with
      mitochondrial DNA-depleted rho0 AL cells, we discovered that mitochondria were
      essential for mediating the synergistic DNA-damaging effects of TiO2 NPs and
      As(III). These data provide novel mechanistic proof that TiO2 NPs enhanced the
      genotoxicity of As(III) via physicochemical interactions, which were mediated by
      mitochondria-dependent ROS.

PMID- 29046142
TI  - The Roles of microRNAs in Regulating Chemotherapy Resistance of Non-Small Cell
      Lung Cancer.
AB  - Lung cancer is considered the leading cause of cancer death in the word. Among
      all lung cancer cases, non-small cell lung cancer (NSCLC) accounts for 85%.
      Currently, chemotherapy is still the major therapeutic method of lung cancer.
      However, chemoresistance is a serious obstacle in treating NSCLC. Up to now, many
      reports have suggested that microRNAs(miRNAs) could contribute to lung cancer
      cell chemosensitivity. MicroRNAs, a class of endogenous non-coding small RNAs,
      regulate gene expression by binding to their complementary target messenger RNAs,
      leading to mRNA degradation or translational suppression. Numerous studies
      indicate that changes of specific miRNA expression may contribute to
      chemoresistance or chemosensitivity. Consequently, targeting specific miRNAs
      could become an effective approach to predict the therapeutic effect of different
      anticancer agents, achieve more effective personalised treatments and enhance
      chemosensitivity. This review summarizes the several major drug resistance
      mechanisms and focuses on the roles of miRNAs in regulating chemoresistance in
      NSCLC.

PMID- 29046143
TI  - Influence of Length and Amino Acid Composition on Dimer Formation of
      Immunoglobulin based Chimera.
AB  - BACKGROUND: The dimeric immunoglobulin (Ig) chimeras used for drug targeting and
      delivery are preferred biologics over their monomeric forms. Designing these Ig
      chimeras involves critical selection of a suitable Ig base that ensures dimer
      formation. In the present study, we systematically analyzed several factors that
      influence the formation of dimeric chimera. We designed and predicted 608
      cytokine-Ig chimeras where we tested the contributions of (1) different domains
      of Ig constant heavy chain, (2) length of partner proteins, (3) amino acid (AA)
      composition and (4) position of cysteine in the formation of homodimer. METHOD:
      The sequences of various Ig and cytokines were procured from Uniprot database,
      fused and submitted to COTH (CO-THreader) server for the prediction of dimer
      formation. Contributions of different domains of Ig constant heavy chain, length
      of chimeric proteins, AA composition and position of cysteine to the homodimer
      formation of 608 cytokine-Ig chimeras were tested. Various in silico approaches
      were adopted for validating the in silico findings. Experimentally we also
      validated our approach by expressing the chimeric design of shorter cytokine with
      Ig domain in CHO cells and analyzing the protein by SDS-PAGE. RESULTS: Our
      results advocate that while the CH1 region and the Hinge region of Ig heavy chain
      are critical, the length of partner proteins also crucially influences homodimer
      formation of the Ig-based chimera. We also report that the CH1 domain of Ig is
      not required for dimer formation of Ig based chimera in the presence of larger
      partner proteins. For shorter partner proteins fused to CH2-CH3, careful
      selection of partner sequence is critical, particularly the hydrophobic AA
      composition, cysteine content & their positions, disulphide bond formation
      property, and the linker sequences. We validated our in silico observation by
      various bioinformatics tools and checked the ability of chimeras to bind with the
      receptors of native protein by docking studies. As a proof of concept, we have
      expressed the chimeric proteins in CHO cells and found that our design favors the
      synthesis of dimeric proteins. CONCLUSION: Our structural prediction study
      suggests that extra amino acids in the range of 15-20 added to the CH2 domain of
      Ig is a critical requirement to make homodimer. This information from our study
      will have implication in designing efficacious homodimeric chimera.

PMID- 29046144
TI  - Purine and Pyrimidine Phosphoribosytransferases: A versatile tool for enzymatic
      synthesis of nucleoside-5'-monophosphates.
AB  - BACKGROUND: In recent years, enzymatic methods have shown to be an efficient and
      sustainable alternative for the synthesis of nucleosides and nucleoside-5'
      monophosphates (NMPs) to the traditional multistep chemical methods, since
      chemical glycosylation reactions include several protection-deprotection steps
      and the use of chemical reagents and organic solvents that are expensive and
      environmentally harmful. RESULTS: In this mini-review, we want to illustrate the
      application of phosphoribosyltransferases (PRTs) in enzymatic synthesis of NMPs.
      In this sense, many different examples about the use of PRTs as biocatalysts, as
      whole cells or enzymes, are described. In addition, it also includes detailed
      comments about structure and catalytic mechanism of described PRTs, as well as
      their possible biological role and therapeutic use, substrate specificity and
      advances in detection of new enzyme specificities towards different substrates.
      In addition, several examples about the use of PRTs in mono or multi-enzymatic
      synthesis of NMP analogues are shown. Finally, a brief discussion about
      advantages and drawbacks of the use of PRTs as industrial biocatalyst of NMPs has
      been commented. CONCLUSION: Despite the great potential of PRTs as biocatalysts
      for industrial synthesis of NMPs, several drawbacks must be overcome before
      reaching a suitable industrial application. In this sense, multi-enzyme systems
      provide an appropriate framework for this purpose. Moreover, future advances in
      different disciplines as protein engineering, bioinformatics and -omics will help
      to reach this goal.

PMID- 29046145
TI  - Experimental Treatment Options in Absence Epilepsy.
AB  - BACKGROUND: The benign character of absence epilepsy compared to other genetic
      generalized epilepsy syndromes has often hampered the search for new treatment
      options. Absence epilepsy is most often treated with ethosuximide or valproic
      acid. However, both drugs are not always well tolerated or fail, and seizure
      freedom for a larger proportion of patients remains to be achieved. The
      availability of genuine animal models of epilepsy does allow to search for new
      treatment options not only for absence epilepsy per se but also for other genetic
      - previously called idiopathic - forms of epilepsy. The recent discovery of a
      highly excitable cortical zone in these models is considered as a new therapeutic
      target area. METHODS: Here, we provide an overview regarding the search for new
      therapeutical options as has been investigated in the genetic rodent models
      (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis can be
      achieved, various types of electrical and optogenetical invasive stimulations,
      different types of noninvasive stimulation and finally whether absence seizures
      can be predicted and prevented. RESULTS: Many factors determine either the
      cortical and or thalamic excitability or the interaction between cortex and
      thalamus and offer new possibilities for new anti-absence drugs, among others
      metabotropic glutamatergic positive and negative allosteric modulators. The
      inhibition of epileptogenesis by various drugs with its widespread consequences
      seems feasible, although its mechanisms remain obscure and seems different from
      the antiabsence action. Surgical intervention on the cortical zone initiating
      seizures, either with radiosurgery using synchrotron- generated microbeams, or
      ablation techniques might reduce spike-and-wave discharges in the rodent models.
      High frequency electrical subcortical or cortical stimulation might be a good way
      to abort ongoing spikeand- wave discharges. In addition, possibilities for
      prevention with real-time EEG analyses in combination with electrical stimulation
      could also be a way to fully control these seizures. CONCLUSION: Although it is
      obvious that some of these treatment possibilities will not be used for absence
      epilepsy and/or need to be further developed, all can be considered as proof of
      principle and provide clear directives for further developments.

PMID- 29046146
TI  - Phospholipid-based Immobilized Artificial Membrane (IAM) Chromatography: A
      Powerful Tool to Model Drug Distribution Processes.
AB  - A review of applications of the Immobilized Artificial Membrane (IAM)
      chromatography in drug discovery is given. IAM chromatography is presented as a
      tool to predict the interactions of solutes with biomembranes, blood-brain
      barrier permeability, volume of distribution, oral and skin absorption of drugs
      and compared to other in vitro techniques used to study drug bioavailability
      (caco-2 cells, liposome partition). Unbound phosphatidylcholine based stationary
      phases are also discussed. Some new trends and ideas in the IAM chromatography
      are presented.

PMID- 29046147
TI  - Neonatal Pain, Still Searching for the Optimal Approach.
AB  - BACKGROUND: although neonatal pain management has seen huge improvements in the
      past years, many gaps between knowledge and practice still exist. OBJECTIVE: to
      give the reader the state of the art of actual pain management and treatment.
      METHODS: a literature review was done on the physiopathology of pain, sex
      differences in the perception of pain, epidemiology, non-pharmacological
      treatment and developmental care approach, pharmacological treatment with
      pharmacokinetics and pharmacodynamics approaches. CONCLUSION: despite an
      increasing knowledge in the field of neonatal pain, many gaps and questions
      remain, especially relative to the lack of assessment, prevention and treatment
      of painful procedures, appropriate drugs and dosing to support the well-being and
      the brain development of this highly vulnerable population.

PMID- 29046148
TI  - Exploring the Unique Selectivity of Hydrophobic Cation Exchanger Nuvia cPrime for
      the Removal of a Major Process Impurity: A Case Study with IgM.
AB  - BACKGROUND: Mixed-mode chromatography is becoming an important tool for
      downstream process purification, as it provides the selectivity and robustness
      unmatched by conventional singlemode chromatographic methods. The joint action of
      multiple functionalities present on the ligands of mixed-mode chromatography
      matrices effectively enhances the separation of target molecules from impurities.
      MATERIAL AND METHODS: Using Nuvia cPrime as an example, we elucidate the
      separation principles of hydrophobic cation exchange mixed-mode chromatography
      and its difference from traditional strong cation exchangers. We have developed a
      Nuvia cPrime based polish purification step specifically for the removal of a
      major process contaminant, which has an isoelectric point similar to that of the
      target monoclonal IgM molecule. Additional purification was accomplished using a
      second mixed-mode chromatography column packed with Ceramic Hydroxyapatite.
      CONCLUSION: The monoclonal IgM prepared with this new process fully retained its
      biological activity and was free of high molecular weight aggregates, a product
      quality that was not achievable in previous attempts using traditional ion
      exchange or hydrophobic interaction chromatography.

PMID- 29046149
TI  - Schizophrenia And Nicotine Dependence: What Psychopharmacological Treatment
      Options Are Available For The Duo Perturbationes?
AB  - Nicotine dependence has progressively become a foremost community health interest
      in the both developed and developing nations due to the economic burden and
      health-related problem. Smoking was significantly higher among patients with
      schizophrenia in comparison to the general population. Nicotine dependence is not
      only associated with public stress, but among patients with schizophrenia,
      smoking brings major challenges to the management. Nicotine may diminish the
      therapeutic efficacy of the bioavailability of the psychopharmacological agents
      in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may
      prevent psychotic symptoms remission among patient suffering from schizophrenia
      who is smoking on the same time. The aim of this review was to highlight the role
      of pharmacological treatment options and strategies for patients with nicotine
      dependence in schizophrenia with emphasis on the underlying neurobiological
      process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine
      reuptake inhibition (NDRI) e.g. Bupropion and selective partial agonist of
      alpha4beta2 and full alpha7-nicotinic acetylcholine receptor e.g. varenicline
      were deliberated. An ideal choice of drug targets for patients with schizophrenia
      with nicotine dependence is pivotal to foster a better therapeutic alliance.

PMID- 29046150
TI  - Complex Interplay Between Solubilization, Digestion, Supersaturation and
      Absorption of Poorly Soluble Drugs with Lipid-Based Formulations.

PMID- 29046151
TI  - Combining Drug-Loaded Nanobubbles and Extracorporeal Shock Waves for Difficult-to
      Treat Cancers.

PMID- 29046152
TI  - Cerebral Small Vessel Disease is Associated with Genetic Variations in CYP2J.
AB  - BACKGROUND: Cerebral Small Vessel Disease (SVD) can cause cognitive impairment,
      disability and dementia. While it is still unclear about the pathogenesis of SVD,
      several risk factors of SVD have been identified, and studies suggested that
      hypertension may play a critical role in SVD. Furthermore, studies have
      demonstrated that CYP2J2 isoform, 50 G>T variant, is associated with increasing
      the risk of ischemic stroke. Thus, we hypothesized that CYP2J2 50 G>T variant is
      associated with increased risk of cerebral SVD. METHODS: Thus, in this case
      control study, we evaluated the association of CYP2J2 polymorphisms with the
      susceptibility to cerebral SVD in a population of Chinese Han adults. RESULTS: We
      found that CYP2J2 50 G>T genotype was significantly higher in SVD patients
      compared to healthy control group. Furthermore, 50 G>T genotype of CYP2J2 was
      associated with a significantly higher risk of SVD. Additionally, this
      polymorphism was significantly associated with WMH volume and a number of
      impaired cognitive domains in SVD patients. CONCLUSION: In conclusion, our study
      demonstrated that CYP2J2 50 G>T polymorphism is associated with increased risk of
      cerebral SVD in Han Chinese.

PMID- 29046153
TI  - Potential Therapeutics for Vascular Cognitive Impairment and Dementia.
AB  - BACKGROUND: As the human lifespan increases, the number of people affected by
      agerelated dementia is growing at an epidemic pace. Vascular pathology
      dramatically affects cognitive profiles, resulting in dementia and cognitive
      impairment. While vascular dementia itself constitutes a medical challenge, hypo
      perfusion/vascular risk factors enhance amyloid toxicity and other memory-
      damaging factors and hasten Alzheimer's disease (AD) and other memory disorders'
      progression, as well as negatively affect treatment outcome. METHODS: Research
      and online content related to vascular cognitive impairment and dementia is
      reviewed, specifically focusing on the potential treatment of the disorder.
      RESULTS: Few therapeutic options are currently available to improve the prognosis
      of patients with vascular dementia and cognitive impairment, mixed AD dementia
      with vascular pathology, or other memory disorders. Emerging evidence, however,
      indicates that, like AD and other memory disorders, synaptic impairment underlies
      much of the memory impairment in the cognitive decline of vascular cognitive
      impairment and vascular dementia. CONCLUSION: Effective rescues of the memory
      functions might be achieved through synaptic and memory therapeutics, targeting
      distinct molecular signaling pathways that support the formation of new synapses
      and maintaining their connections. Potential therapeutic agents include: 1)
      memory therapeutic agents that rescue synaptic and memory functions after the
      brain insults; 2) antipathologic therapeutics and an effective management of
      vascular risk factors; and 3) preventative therapeutic agents that achieve memory
      therapy through functional enhancement. These therapeutic agents are also likely
      to benefit patients with AD and/or other types of memory disorders.

PMID- 29046154
TI  - Neural Network Alterations Across Eating Disorders: A Narrative Review of fMRI
      Studies.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) has provided insight on
      how neural abnormalities are related to the symptomatology of the eating
      disorders (EDs): anorexia nervosa (AN), bulimia nervosa (BN), and binge eating
      disorder (BED). More specifically, an increasingly growing number of brain
      imaging studies has shed light on how functionally connected brain networks
      contribute not only to disturbed eating behavior, but also to transdiagnostic
      alterations in body/interoceptive perception, reward processing and executive
      functioning. METHODS: This narrative review aims to summarize recent advances in
      fMRI studies of patients with EDs by highlighting studies investigating network
      alterations that are shared across EDs. RESULTS AND CONCLUSION: Findings on
      reward processing in both AN and BN patients point to the presence of altered
      sensitivity to salient food stimuli in striatal regions and to the possibility of
      hypothalamic inputs being overridden by top-down emotional-cognitive control
      regions. Additionally, innovative new lines of research suggest that increased
      activations in fronto-striatal circuits are strongly associated with the
      maintenance of restrictive eating habits in AN patients. Although significantly
      fewer studies have been carried out in patients with BN and BED, aberrant neural
      responses to both food cues and anticipated food receipt appear to occur in these
      populations. These altered responses, coupled with diminished recruitment of
      prefrontal cognitive control circuitry, are believed to contribute to the binge
      eating of palatable foods. Results from functional network connectivity studies
      are diverse, but findings tend to converge on indicating disrupted resting-state
      connectivity in executive networks, the default-mode network and the salience
      network across EDs.

PMID- 29046156
TI  - Computer Aided Drug Design and its Application to the Development of Potential
      Drugs for Neurodegenerative Disorders.
AB  - BACKGROUND: Neurodegenerative disorders (NDs) are diverse group of disorders
      characterized by escalating loss of neurons (structural and functional). The
      development of potential therapeutics for NDs presents an important challenge, as
      traditional treatments are inefficient and usually are unable to stop or retard
      the process of neurodegeneration. Computer-Aided Drug Design (CADD) has emerged
      as an efficient means of developing candidate drugs for the treatment of many
      disease types. Applications of CADD approach to drug discovery are progressing
      day by day. The recent tendency in drug design is to rationally design potent
      therapeutics with multi-targeting effects, higher efficacies, and fewer side
      effects, especially in terms of toxicity. METHODS: A wide literature search was
      performed for writing this review. An updated view on different types of NDs,
      their effect on human population and a brief introduction to CADD, various
      approaches involved in this technique, ranging from structural-based to ligand
      based drug design has been discussed. The successful application of CADD
      approaches for the treatment of neurodegenerative disorders is also included in
      this review. RESULTS: In this review, we have briefly described about CADD and
      its use in the development of the therapeutic drug candidates against NDs. The
      successful applications, limitations and future prospects of this approach have
      also been discussed. CONCLUSION: CADD can assist researchers studying
      interactions between drugs and receptors. We believe this review will be helpful
      for better understanding of CADD and its applications towards the discovery of
      new drug candidates against various fatal NDs.

PMID- 29046157
TI  - Blood Brain Barrier and Alzheimer's Disease: Similarity and Dissimilarity of
      Molecular Alerts.
AB  - BACKGROUND: Blood brain barrier and Alzheimer's disease are interrelated. This
      interrelation is detected by physicochemical methods, pharmacological and
      electrophysiological analyses. Nature of the phenomenon is extremely complex. The
      description of this interrelation in mathematical terms is a very important task.
      OBJECTIVE: The systematization of facts, which are described in the literature
      and related to interaction between processes, which influence Alzheimer's disease
      and blood brain barrier is the subject of this work. In addition, establishing of
      correlations between molecular features and endpoints, which are related to the
      treatment of Alzheimer's disease and blood brain barrier using the CORAL software
      are subjects of this work. METHODS: The information on logically structured
      analysis is available in the literature and building up quantitative structure -
      activity relationships (QSARs) by the Monte Carlo method has been used to solve
      the task of systematization of facts related to the "treatment of Alzheimer's
      disease vs. blood brain barrier". RESULTS: Comparison of agreements and
      disagreements of the available published papers together with the statistical
      quality of built up QSARs are results of this work. CONCLUSION: The facts from
      published papers and technical details of QSAR built up in this study give
      possibility to formulate the following rules: (i) there are molecular alerts,
      which are promoters to increase blood brain barrier and therapeutic activity of
      anti-Alzheimer disease agents; (ii) there are molecular alerts, which contradict
      each other.

PMID- 29046159
TI  - Pilot Integration of HIV Screening and Healthcare Settings with Multi- Component
      Social Network and Partner Testing for HIV Detection.
AB  - BACKGROUND: Healthcare settings screen broadly for HIV. Public health settings
      use social network and partner testing ("Transmission Network Targeting (TNT)")
      to select high-risk individuals based on their contacts. HIV screening and TNT
      systems are not integrated, and healthcare settings have not implemented TNT.
      OBJECTIVE: The study aimed to evaluate pilot implementation of multi-component,
      multi-venue TNT in conjunction with HIV screening by a healthcare setting.
      METHODS: Our urban, academic health center implemented a TNT program in
      collaboration with the local health department for five months during 2011. High
      risk or HIV positive patients of the infectious diseases clinic and emergency
      department HIV screening program were recruited to access social and partner
      networks via compensated peer-referral, testing of companions present with them,
      and partner notification services. Contacts became the next-generation index
      cases in a snowball recruitment strategy. RESULTS: The pilot TNT program yielded
      485 HIV tests for 482 individuals through eight generations of recruitment with
      five (1.0%; 95% CI = 0.4%, 2.3%) new diagnoses. Of these, 246 (51.0%; 95% CI =
      46.6%, 55.5%) reported that they had not been tested for HIV within the last 12
      months and 383 (79.5%; 95% CI = 75.7%, 82.9%) had not been tested by the existing
      ED screening program within the last five years. CONCLUSION: TNT complements
      population screening by more directly targeting high-risk individuals and by
      expanding the population receiving testing. Information from existing healthcare
      services could be used to seed TNT programs, or TNT could be implemented within
      healthcare settings. Research evaluating multi-component, multi-venue HIV
      detection is necessary to maximize complementary approaches while minimizing
      redundancy.

PMID- 29046160
TI  - Construction and Production of HIV-VLP Harboring MPER-V3 for Potential Vaccine
      Study.
AB  - BACKGROUND: Vaccine against HIV-1 is not currently available. In present, Virus
      like particles (VLPs) as effective strategy was used in several vaccine
      developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal
      external region (MPER) of gp41 are dominant sites for vaccine studies. OBJECTIVE:
      In this study, we used fusion gene of MPER and V3 to product recombinant VLPs and
      introduced a novel retroviral VLPs harboring high copy of MPER-V3 for HIV-1
      vaccine design. METHODS: The pEGFP-N1 plasmid harboring MPER-V3 sequence with Vpr
      linker was constructed. To produce virus-like particles, HEK 293T cells were co
      transfected with the recombinant plasmid, pSPAX-2, pMD2-G and pWPXLd plasmids,
      evaluated by AFM and SEM microscopy and quantified using P24 end-point ELISA
      assay. RESULTS: Time-course quantification of p24 protein as the characteristics
      of viral production evidenced for the efficient secretion of virus-like
      structures (up to 120 ng/ml) to the culture supernatant of transfected cells.
      Examination of the centrifuge-concentrated VLPs by AFM and SEM microscope, also
      illustrated particles with spherical morphologies and diameters of around 150 nm
      that had similar sizes to HIV virions. CONCLUSION: These data indicated the
      production of HIV-1 virus-like particles harboring high copy of MPER-V3 that
      maintained their antigenic structure. These VLPs represented a good implication
      as a potential vaccine candidate and this guarantees the further investigations
      towards the assessment of its immunogenicity.

PMID- 29046155
TI  - Impact of Dietary Fats on Brain Functions.
AB  - BACKGROUND: Adequate dietary intake and nutritional status have important effects
      on brain functions and on brain health. Energy intake and specific nutrients
      excess or deficiency from diet differently affect cognitive processes, emotions,
      behaviour, neuroendocrine functions and synaptic plasticity with possible
      protective or detrimental effects on neuronal physiology. Lipids, in particular,
      play structural and functional roles in neurons. Here the importance of dietary
      fats and the need to understand the brain mechanisms activated by peripheral and
      central metabolic sensors. Thus, the manipulation of lifestyle factors such as
      dietary interventions may represent a successful therapeutic approach to maintain
      and preserve brain health along lifespan. METHODS: This review aims at
      summarizing the impact of dietary fats on brain functions. RESULTS: Starting from
      fat consumption, nutrient sensing and food-related reward, the impact of gut
      brain communications will be discussed in brain health and disease. A specific
      focus will be on the impact of fats on the molecular pathways within the
      hypothalamus involved in the control of reproduction via the expression and the
      release of Gonadotropin-Releasing Hormone. Lastly, the effects of specific lipid
      classes such as polyunsaturated fatty acids and of the "fattest" of all diets,
      commonly known as "ketogenic diets", on brain functions will also be discussed.
      CONCLUSION: Despite the knowledge of the molecular mechanisms is still a work in
      progress, the clinical relevance of the manipulation of dietary fats is well
      acknowledged and such manipulations are in fact currently in use for the
      treatment of brain diseases.

PMID- 29046161
TI  - Inhaled Nitric Oxide in Preterm Neonates with Refractory Hypoxemia Associated to
      Oligohydramnios.
AB  - BACKGROUND: Therapy with inhaled nitric oxide (iNO) is effective in the
      management of pulmonary hypertension and severe hypoxemia. However, these
      benefits have not been demonstrated in preterm infants (<34 weeks). The objective
      of this report is to present the experience of eight cases of preterm neonates
      with respiratory distress syndrome (RDS) and refractory hypoxemia, with
      oligohydramnios history. METHODS: We evaluated the clinical feature of 8 preterm
      neonates with severe hypoxemia who had maternal antecedents of oligoamnios,
      mainly due to premature rupture of membranes. They were treated with conventional
      management, with poor clinical response. Therefore, these neonates were treated
      with iNO, as a rescue strategy. iNO has been used with a dosage of 5 - 10 ppm. An
      echocardiogram was performed to determine the presence of structural
      malformations or persistent ductus arteriosus. RESULTS: All the infants showed
      improvement in oxygenation. The neonates had signs of low flow pulmonary,
      confirmed by echocardiogram. Five preterm infants survived without complications
      associated with the therapy. Two died from pulmonary bleeding secondary to ductus
      arteriosus and another for pneumothorax. CONCLUSION: iNO therapy can be useful in
      a subgroup of preterm infants with a high risk of death secondary to hypoxemia.
      Although this report is based on a small number of cases, it follows the
      directions of other studies that suggest that iNO therapy can benefit preterm
      neonates, particularly those exposed to oligohydramnios.

PMID- 29046158
TI  - E-cigarettes: Impact of E-Liquid Components and Device Characteristics on
      Nicotine Exposure.
AB  - BACKGROUND: Electronic cigarette (e-cigarette) use has increased substantially in
      recent years. While e-cigarettes have been proposed as a potentially effective
      smoking cessation tool, dualuse in smokers is common and e-cigarettes are widely
      used by non-smokers, including youth and young-adult non-smokers. Nicotine, the
      primary addictive component in cigarettes, is present at varying levels in many e
      liquids. E-cigarettes may lead to initiation of nicotine use in adult and youth
      non-smokers, re-initiation of nicotine dependence in ex-smokers or increased
      severity of nicotine dependence in dual-users of cigarettes and e-cigarettes. As
      such, there are important clinical and policy implications to understanding
      factors impacting nicotine exposure from e-cigarettes. However, the broad and
      rapidly changing range of e-liquid constituents and e-cigarette hardware which
      could impact nicotine exposure presents a challenge. Recent changes in regulatory
      oversight of e-cigarettes underscore the importance of synthesizing current
      knowledge on common factors which may impact nicotine exposure. METHODS: This
      review focuses on factors which may impact nicotine exposure by changing e
      cigarette use behavior, puff topography, altering the nicotine yield (amount of
      nicotine exiting the e-cigarette mouth piece including nicotine exhaled as vapor)
      or more directly by altering nicotine absorption and bioavailability. RESULTS:
      Topics reviewed include e-liquid components or characteristics including flavor
      additives (e.g., menthol), base e-liquid ingredients (propylene glycol, vegetable
      glycerin), components commonly used to dissolve flavorants (e.g., ethanol), and
      resulting properties of the e-liquid (e.g., pH), e-cigarette device
      characteristics (e.g., wattage, temperature, model) and user behavior (e.g., puff
      topography) which may impact nicotine exposure. CONCLUSION: E-liquid
      characteristics and components, e-cigarette hardware and settings, and user
      behavior can all contribute substantially to nicotine exposure from e-cigarettes.

PMID- 29046163
TI  - Application of Hydrogels in Cartilage Tissue Engineering.
AB  - BACKGROUND: Cartilage has limited ability for self-repairing, prompting the
      search for cartilage substitutes that can repair cartilage defects. Hydrogels
      have attracted attention as cartilage substitutes, since their mechanical
      properties, swelling ability and lubricating behavior are similar to
      extracellular matrix of articular cartilage. Hydrogels can be of natural,
      synthetic or hybrid origin, and hydrogels can encapsulate stem cells and/or be
      loaded with growth factors to promote cell differentiation into a chondrogenic
      phenotype. OBJECTIVE AND RESULTS: This review summarizes basic research advances
      in using hydrogels to repair cartilage defects. The raw materials, stem cells and
      growth factors used to prepare hydrogels are discussed. CONCLUSION: Substantial
      success has been achieved in small animal models of cartilage repair and
      regeneration, but further research is needed to improve hydrogels' mechanical
      properties and their integration with surrounding tissues.

PMID- 29046162
TI  - Potential Role of Rebamipide in Osteoclast Differentiation and Mandibular
      Condylar Cartilage Homeostasis.
AB  - BACKGROUND: Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative
      disease that involves changes in subchondral bone and progressive degradation of
      cartilage. Currently, rebamipide, a gastroprotective drug, is administered to
      protect gastric mucosa and accelerate ulcer healing. OBJECTIVES: Recent studies
      have shown that rebamipide also attenuates cartilage degeneration by suppressing
      oxidative damage and inducing homeostasis of the extracellular matrix of
      articular chondrocytes. Regarding the latter, reduced expression of cathepsin K,
      NFATc1, c-Src, and integrin beta3, and increased expression of nuclear factor
      kappa B, have been found to be mediated by the transcription factor, receptor
      activator of nuclear factor kappa-B ligand (RANKL). METHODS: Treatment with
      rebamipide was also found to activate, mitogen-activated protein kinases such as
      p38, ERK, and JNK to reduce osteoclast differentiation. Taken together, these
      results strongly indicate that rebamipide mediates inhibitory effects on
      cartilage degradation and osteoclastogenesis in TMJ-OA. RESULTS AND CONCLUSION:
      Here, we highlight recent evidence regarding the potential for rebamipide to
      affect osteoclast differentiation and TMJ-OA pathogenesis. We also discuss the
      potential role of rebamipide to serve as a new strategy for the treatment of TMJ
      OA.

PMID- 29046164
TI  - Colchicine: A Review on Chemical Structure and Clinical Usage.
AB  - For many years, colchicine has been used for therapeutic purposes and has been
      given considerable attention because of its association with tubulin and
      inhibition of small tubular polymerization. Colchicine is an alkaloid extracted
      from the colchicum autumnale plant, having molecular formula C22H25NO6, and
      consists of three rings. Many studies are concerned with structural changes in
      order to increase their pharmacological effectiveness and reduce the side effects
      of toxicity arising from it. The therapeutic use of colchicine has been mainly
      documented in Gout, Familial Mediterranean Fever, and many other diseases such as
      atrial fibrillation. This review summarizes the history of chemical structure of
      colchicine and presents some of its analogues. Furthermore, it shows binding
      mechanism with target protein when colchicine is used as a therapeutic drug, and
      gives a light spot on some studies that discuss the safe use of colchicine.

PMID- 29046165
TI  - Long-Term Use of Nimotuzumab in Combination With Intensity-Modulated Radiotherapy
      and Chemotherapy in the Treatment of Locoregionally Advanced Nasopharyngeal
      Carcinoma: Experience of a Single Institution.
AB  - In this retrospective review of a single institution's experience, the efficacy
      and safety of the long-term use of nimotuzumab in combination with intensity
      modulated radiotherapy (IMRT) and chemotherapy in the treatment of locally
      advanced nasopharyngeal carcinoma (NPC) were studied. Between August 2008 and
      March 2014, 39 newly diagnosed patients with stages III-IV NPC were treated with
      IMRT, chemotherapy, and nimotuzumab. Twenty patients were diagnosed with stage
      III (51.3%), 14 with stage IVA (35.9%), and 5 with stage IVB (12.8%) disease. All
      patients received at least one cycle of cisplatin-based induction chemotherapy
      followed by IMRT and more than nine cycles of nimotuzumab at 200 mg/week. Acute
      and late radiation-related toxicities were graded according to the Acute and Late
      Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.
      Accumulated survival was calculated according to the Kaplan-Meier method. The log
      rank test was used to compare survival differences. With a median follow-up of 46
      months (range, 22-86 months), the estimated 3-year local recurrence-free,
      regional recurrence-free, distant metastasis-free, progression failure-free, and
      overall survival rates were 92.1%, 89.7%, 82.5%, 77.6%, and 86.8%, respectively.
      Univariate analysis showed that clinical stage and the cycle of induction
      chemotherapy were related with prognosis. The median cycle for the addition of
      nimotuzumab was 12 weeks. Grade 3 radiation-induced mucositis was observed in
      15.8% of the treated patients. No skin rash or infusion reaction was observed,
      which is distinctly different from what was reported in patients treated with
      nimotuzumab. The major toxicities observed were grades I-II mucositis and
      leukocytopenia. Long-term use of nimotuzumab plus IMRT showed promising outcomes
      in terms of locoregional control and survival, without increasing the incidence
      of radiation-related toxicities in patients.

PMID- 29046166
TI  - Evaluation of mericon E. coli O157 Screen Plus and mericon E. coli STEC O-Type
      Pathogen Detection Assays in Select Foods: Collaborative Study, First Action
      2017.05.
AB  - QIAGEN mericon Escherichia coli O157 Screen Plus and mericon E. coli Shiga toxin
      producing E. coli (STEC) O-Type Pathogen Detection Assays use Real-Time PCR
      technology for the rapid, accurate detection of E. coli O157 and the "big six"
      (O26, O45, O103, O111, O121, O145) (non-O157 STEC) in select food types. Using a
      paired study design, the assays were compared with the U.S. Department of
      Agriculture, Food Safety Inspection Service Microbiology Laboratory Guidebook
      Chapter 5.09 reference method for the detection of E. coli O157:H7 in raw ground
      beef. Both mericon assays were evaluated using the manual and an automated DNA
      extraction method. Thirteen technicians from five laboratories located within the
      continental United States participated in the collaborative study. Three levels
      of contamination were evaluated. Statistical analysis was conducted according to
      the probability of detection (POD) statistical model. Results obtained for the
      low-inoculum level test portions produced a difference between laboratories POD
      (dLPOD) value with a 95% confidence interval of 0.00 (-0.12, 0.12) for the
      mericon E. coli O157 Screen Plus with manual and automated extraction and mericon
      E. coli STEC O-Type with manual extraction and -0.01 (-0.13, 0.10) for the
      mericon E. coli STEC O-Type with automated extraction. The dLPOD results indicate
      equivalence between the candidate methods and the reference method.

PMID- 29046168
TI  - Combined treatment of mezcal vinasses by ozonation and activated sludge.
AB  - In Mexico, mezcal production generates huge amounts of vinasses (MV) that cause
      negative environmental impacts. Thus, MV treatment is necessary before discharge
      to water bodies. Although there is no information for mezcal vinasses, similar
      effluents have been treated by biological processes (i.e. anaerobic and aerobic)
      usually complemented by oxidative chemical pretreatments (ozonation) and physico
      chemical methods. In this work MV were first ozonated and followed by batch
      aerobic biological degradation. In the ozonation stage, organic matter removals
      were 4.5-11 % as COD, whereas the removal of aromatic compounds and phenols were
      16-32 % and 48-83 % respectively. In the aerobic post-treatment, COD depletions
      up to 85 % were achieved; removals in ozone pre-treated vinasses were higher (80
      to 85 %) than that of raw vinasse (69 %). It seems that ozonation preferentially
      attacked the recalcitrant fraction of organic matter present in the vinasses and
      increased its aerobic biodegradability.

PMID- 29046167
TI  - Non-SMC Condensin I Complex, Subunit G (NCAPG) is a Novel Mitotic Gene Required
      for Hepatocellular Cancer Cell Proliferation and Migration.
AB  - Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related
      deaths worldwide. Currently, only chemoembolization and sorafenib have shown
      survival benefits for advanced HCC. There are major unmet needs in HCC management
      and the discovery of new therapeutic targets. Here we identified NCAPG (non-SMC
      condensin I complex, subunit G) as a novel mitotic gene required for HCC cell
      proliferation and migration through siRNA knockdown of a panel of novel
      overexpressed genes in HCC based on The Cancer Genome Atlas (TCGA) dataset. We
      found that knockdown of NCAPG induces HCC cell mitosis and inhibits cell growth,
      proliferation, and migration in vitro. Tetracycline-inducible shRNA knockdown of
      NCAPG inhibits tumor growth of HCC cells in vivo. Moreover, overexpression of
      NCAPG in clinical HCC samples was associated with recurrence and survival of
      patients. The overexpression of NCAPG was significantly correlated with the
      overexpression of CCNB1 (G2/mitotic-specific cyclin B1), a regulatory protein
      involved in mitosis. Therefore, NCAPG may provide a promising novel therapeutic
      target for the treatment of advanced HCC in the future.

PMID- 29046169
TI  - Response of Epiphytic Algae to Heavy Pollution of Water Bodies.
AB  - The objective of the present work was to study the structure of epiphyton in
      water bodies significantly differing in the degree of their contamination. In the
      studied water bodies, the concentration of ammonia (<inline-graphic
      xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00706-ilm01.gif"/>)
      accounted for 0.04-74.00 mg/L; nitrite (<inline-graphic
      xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="00706-ilm02.gif"/>), 0.002
      1.750 mg/L; nitrate (<inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink"
      xlink:href="00706-ilm03.gif"/>), 0.13-58.00 mg/L; inorganic compounds of
      phosphorus (Pinorg), 0.041-0.272 mg/L; chloride (Cl-), 34.5-560.5 mg/L; whereas
      the content of organic matter (DO) was 18.0-81.0 mg O/L. The numbers of algae
      were determined by a direct count. Biomass was calculated by the count cell
      volume method. The Generic Diatom Index, the Pantle-Buck saprobic index, and the
      Shannon index of species diversity were used to analyze algal community
      structure. This study found that epiphyton responded to heavy pollution with
      changes in its species richness, taxonomic structure, species composition,
      quantitative indices, numbers and biomass structure, dominant complex, and
      ecological spectrum.

PMID- 29046171
TI  - The Pursuit of Excellence.

PMID- 29046172
TI  - Readability of New Aviation Chart Symbology in Day and NVG Reading Conditions.
AB  - BACKGROUND: The Swedish Air Force (SwAF) conducted a study in 2010 to harmonize
      portrayal of aeronautical info (AI) on SwAF charts with NATO standards. A
      mismatch was found concerning vertical obstructions (VO). Norway regarded
      Sweden's existing symbology as a way to solve the problem of overcrowded air
      charts and the two countries started to cooperate. The result of this development
      was a new set of symbology for obstacles. The aim of this study was to test the
      readability of the new obstacle and power line symbols compared to the old
      symbols. We also wished to assess the readability in NVG illumination conditions,
      particularly regarding the new symbols compared to the old. METHODS: In a
      randomized controlled study design, 21 volunteer military pilots from the
      Norwegian and Swedish Air Force were asked to perform tracking and chart-reading
      tests. The chart-reading test scored both errors and readability using a
      predefined score index. Subjective scoring was also done at the end of the test
      day. RESULTS: Overall response time improved by approximately 20% using the new
      symbology and error rate decreased by approximately 30-90% where statistically
      significant differences were found. DISCUSSION: The tracking test turned out to
      be too difficult due to several factors in the experimental design. Even though
      some caution should be shown in drawing conclusions from this study, the general
      trends seem well supported with the number of aircrew subjects we were able to
      recruit.Wagstaff AS, Larsen T. Readability of new aviation chart symbology in day
      and NVG reading conditions. Aerosp Med Hum Perform. 2017; 88(11):978-984.

PMID- 29046173
TI  - Effects of Physical Driving Experience on Body Movement and Motion Sickness
      During Virtual Driving.
AB  - BACKGROUND: In previous research on motion sickness in simulated and virtual
      vehicles, subjects' experience controlling the corresponding physical vehicles
      has been confounded with their age. During driving of virtual automobiles in a
      video game, we separated chronological age from experience driving physical
      automobiles. METHODS: Subjects drove a virtual automobile in a driving video
      game. Drivers were young adults with several years of experience driving physical
      automobiles, while nondrivers were individuals in the same age group who did not
      have a driver's license and had never driven an automobile. During virtual
      driving, we monitored movement of the head and torso. We collected independent
      measures of the incidence and severity of motion sickness. RESULTS: After virtual
      driving, motion sickness incidence did not differ between drivers (65%) and
      nondrivers (60%). Game performance and the severity of symptoms also did not
      differ between drivers and nondrivers. However, movement differed between
      subjects who later became motion sick and those who did not. In addition,
      physical driving experience influenced patterns of postural activity that
      preceded motion sickness during virtual driving. CONCLUSIONS: The results are
      consistent with the postural instability theory of motion sickness, and help to
      illuminate relationships between the control of physical and virtual
      vehicles.Chang C-H, Chen F-C, Kung W-C, Stoffregen TA. Effects of physical
      driving experience on body movement and motion sickness during virtual driving.
      Aerosp Med Hum Perform. 2017; 88(11):985-992.

PMID- 29046174
TI  - Gravitational and Somatosensory Influences on Control and Perception of Roll
      Balance.
AB  - INTRODUCTION: Blindfolded subjects used a joystick to orient themselves to the
      direction of balance in a device programmed to exhibit inverted pendulum behavior
      in the roll plane; they indicated with a trigger press when they were at that
      location. Our goal was to determine how otolith and somatosensory information
      about the gravitational vertical influenced the ability to locate the direction
      of balance. METHODS: The subjects (N = 12) were tested in each of three
      orientations of the body roll plane: vertical (Upright), 45 degrees  back
      (45_Degree), and 90 degrees  back (Supine), which provided progressively less
      salient otolith and somatosensory information about roll orientation with regard
      to the direction of gravity. For each pitch plane, subjects were tested with
      three directions of balance: 0 degrees  (aligned with the gravitational vertical
      in the Upright condition) and 30 degrees  right or left. RESULTS: The mean
      achieved and indicated orientations for the Upright and 45_Degree conditions were
      significantly displaced away from the direction of balance in the direction of
      gravity, with indicated angles less displaced. In the Supine condition, the mean
      achieved and indicated angles were closer to the direction of balance, but their
      within-trial standard deviations were significantly larger than in the Upright
      and 45_Degree conditions, which did not differ. This greater variability resulted
      from the frequent side to side "drifting" behavior that was a characteristic
      feature of the Supine condition only. DISCUSSION: These findings indicate that in
      the absence of vision accurate dynamic orientation requires gravity dependent
      shear forces on the otolith organs and body surface.Panic AS, Panic H, DiZio P,
      Lackner JR. Gravitational and somatosensory influences on control and perception
      of roll balance. Aerosp Med Hum Perform. 2017; 88(11):993-999.

PMID- 29046175
TI  - Risk Factors for Cervical Pain in F-15C Pilots.
AB  - INTRODUCTION: Many fighter pilots report cervical pain during their careers.
      Etiology likely relates to +Gz exposure, physical positioning with maneuvers, and
      varying load associated with headgear. We evaluated whether selected risk factors
      predicted cervical pain in this population. METHODS: An Institutional Review
      Board-approved, Health Insurance Portability and Accountability Act-compliant,
      controlled crossover study of the use of home cervical traction was undertaken
      with 20 male F-15C pilots. We recorded pilot age (mean 38 yr, range 34-49), total
      high-G hours (2338 h, range 1038-4645), and previous neck problems and measured
      cervical range of motion. For 12 wk, pilots logged pre- and postflight pain,
      whether the Joint Helmet Mounted Cueing System (JHMCS) was employed, maximum +Gz
      experienced, and sortie duration. Pain with and without JHMCS was compared using
      paired t-tests and correlations assessed with Pearson or Spearman coefficients.
      RESULTS: Mean flight-related pain increased by 0.73 on the numerical rating scale
      with JHMCS and 0.52 without. Neck extension coupled with JHMCS use correlated
      negatively with increased pain (r = -0.551). Higher numbers of previously
      reported neck problems correlated with pain when using JHMCS (r = 0.629). Age,
      maximum +Gz per sortie, total high-Gz hours flown, and hours per sortie did not
      correlate. DISCUSSION: To our knowledge, this is the first prospective evaluation
      of risk factors for fighter pilots' cervical pain. Neck pain was significantly
      worse with JHMCS use and with flexed posture or history of prior neck problems
      combined with JHMCS use. This information will help guide countermeasure
      development for high-G pilots.Chumbley EM, Stolfi A, McEachen JC. Risk factors
      for cervical pain in F-15C pilots. Aerosp Med Hum Perform. 2017; 88(11):1000
      1007.

PMID- 29046176
TI  - Dysrhythmias in Laypersons During Centrifuge-Simulated Suborbital Spaceflight.
AB  - INTRODUCTION: There are limited data on cardiac dysrhythmias in laypersons during
      hypergravity exposure. We report layperson electrocardiograph (ECG) findings and
      tolerance of dysrhythmias during centrifuge-simulated suborbital spaceflight.
      METHODS: Volunteers participated in varied-length centrifuge training programs of
      2-7 centrifuge runs over 0.5-2 d, culminating in two simulated suborbital
      spaceflights of combined +Gz and +Gx (peak +4.0 Gz, +6.0 Gx, duration 5 s).
      Monitors recorded pre- and post-run mean arterial blood pressure (MAP), 6-s
      average heart rate (HR) collected at prespecified points during exposures,
      documented dysrhythmias observed on continuous 3-lead ECG, self-reported
      symptoms, and objective signs of intolerance on real-time video monitoring.
      RESULTS: Participating in the study were 148 subjects (43 women). Documented
      dysrhythmias included sinus pause (N = 5), couplet premature ventricular
      contractions (N = 4), bigeminy (N = 3), accelerated idioventricular rhythm (N =
      1), and relative bradycardia (RB, defined as a transient HR drop of >20 bpm; N =
      63). None were associated with subjective symptoms or objective signs of
      acceleration intolerance. Episodes of RB occurred only during +Gx exposures.
      Subjects had a higher post-run vs. pre-run MAP after all exposures, but
      demonstrated no difference in pre- and post-run HR. RB was more common in men,
      younger individuals, and subjects experiencing more centrifuge runs. DISCUSSION:
      Dysrhythmias in laypersons undergoing simulated suborbital spaceflight were well
      tolerated, though RB was frequently noted during short-duration +Gx exposure. No
      subjects demonstrated associated symptoms or objective hemodynamic sequelae from
      these events. Even so, heightened caution remains warranted when monitoring
      dysrhythmias in laypersons with significant cardiopulmonary disease or taking
      medications that modulate cardiac conduction.Suresh R, Blue RS, Mathers CH,
      Castleberry TL, Vanderploeg JM. Dysrhythmias in laypersons during centrifuge
      stimulated suborbital spaceflight. Aerosp Med Hum Perform. 2017; 88(11):1008
      1015.

PMID- 29046177
TI  - Incidents and Injuries in Foot-Launched Flying Extreme Sports.
AB  - BACKGROUND: Participation rates in extreme sports have grown exponentially in the
      last 40 yr, often surpassing traditional sporting activities. The purpose of this
      study was to examine injury rates in foot-launched flying sports, i.e., sports in
      which a pilot foot-launches into flight with a wing already deployed. METHODS:
      This paper is based on a retrospective analysis of the reports of incidents that
      occurred between 2000 and 2014 among the British Hang Gliding and Paragliding
      Association members. RESULTS: The majority of the 1411 reported injuries were in
      the lower limb, followed by the upper limb. The most common lower limb injury was
      to the ankle and included fractures, sprains, and dislocations. The distribution
      of injures was different in each discipline. The calculated yearly fatality rate
      (fatalities/100,000 participants) was 40.4 in hang gliding, 47.1 in paragliding,
      61.9 in powered hang gliding and 83.4 in powered paragliding; the overall value
      for foot-launched flight sports was 43.9. DISCUSSION: Significant differences in
      injury rates and injury patterns were found among different sport disciplines
      that can be useful to steer research on safety, and adopt specific safety rules
      about flying, protective clothing and safety systems in each of these
      sports.Feletti F, Aliverti A, Henjum M, Tarabini M, Brymer E. Incidents and
      injuries in foot-launched flying extreme sports. Aerosp Med Hum Perform. 2017;
      88(11):1016-1023.

PMID- 29046178
TI  - A Psychiatric Formulary for Long-Duration Spaceflight.
AB  - INTRODUCTION: Behavioral health is essential for the safety, well-being, and
      performance of crewmembers in both human spaceflight and Antarctic exploration.
      Over the past five decades, psychiatric issues have been documented in orbital
      spaceflight. In Antarctica, literature suggests up to 5% of wintering crewmembers
      could meet criteria for a psychiatric illness, including mood disorders, stressor
      related disorders, sleep-wake disorders, and substance-related disorders.
      Experience from these settings indicates that psychiatric disorders on deep space
      missions must be anticipated. An important part of planning for the psychological
      health of crewmembers is the onboard provision of psychotropic drugs. These
      medications have been available on orbital missions. A greater variety and supply
      of these drugs exist at Antarctic facilities. The size and diversity of a deep
      space psychiatric formulary will be greater than that provided on orbital
      missions. Drugs to be provisioned include anxiolytics, antidepressants, mood
      stabilizers, antipsychotics, and hypnotics. Each drug category should include
      different medications, providing diverse pharmacokinetic, pharmacodynamic, and
      side effect profiles. The formulary itself should be rigorously controlled, given
      the abuse potential of some medications. In-flight treatment strategies could
      include psychological monitoring of well-being and early intervention for
      significant symptoms. Psychiatric emergencies would be treated aggressively with
      behavioral and pharmacological interventions to de-escalate potentially hazardous
      situations. On long-duration space missions, a robust psychiatric formulary could
      provide crewmembers autonomy and flexibility in treating a range of behavioral
      issues from depression to acute psychosis. This will contribute to the safety,
      health, and performance of crewmembers, and to mission success.Friedman E, Bui B.
      A psychiatric formulary for long-duration spaceflight. Aerosp Med Hum Perform.
      2017; 88(11):1024-1033.

PMID- 29046179
TI  - Coping and Changes in Arousal After Exposure to +Gz Load.
AB  - BACKGROUND: Acceleration load causes several physiological changes that play
      important roles in pilot performance. One of the problems is determining
      individual factors responsible for the differences in changes in the level of
      central nervous system (CNS) arousal after exposure to acceleration loads. We
      were interested in whether the coping style and anxiety as a trait might
      differentiate the subjects in terms of reactions of the CNS to +Gz load-related
      stress. METHODS: Examined were 31 male volunteers with ages between 23 and 30 yr.
      Measurements were obtained under controlled conditions before, during, and every
      2 min up to 12 min after centrifugation. The study was conducted using the Coping
      Inventory for Stressful Situations (CISS) and State Trait Anxiety Inventory. The
      value of Critical Flicker Fusion Threshold (CFFT) corresponded to the level of
      CNS arousal. RESULTS: Two significantly different trends of changes in CNS
      arousal were identified: class 1 (higher level of fatigue following +Gz load) and
      class 2 (lower level of fatigue following +Gz load). Significant differences were
      observed in CISS scores with Task-Oriented Coping value in class 1 (M = 65.94, SD
      = 5.47) being considerably greater than in class 2 (M = 62, SD = 4.37). For
      Emotion-Oriented and Distraction Coping, the mean value in class 1 (M = 29.53, SD
      = 7.72; M = 16.82, SD = 3.8) was significantly lower than in class 2 (M = 34.33,
      SD = 6.68; M = 19.42, SD = 3.4). DISCUSSION: The nature of the changes in CFFT
      values over time is associated with coping style. Coping styles are very valuable
      in the prediction of CNS arousal caused by exposure to +Gz stress.Biernacki MP,
      Lewkowicz R, Zielinski P, Wojtkowiak M. Coping and changes in arousal after
      exposure to +Gz load. Aerosp Med Hum Perform. 2017; 88(11):1034-1039.

PMID- 29046180
TI  - Aircrew and Handheld Laser Exposure.
AB  - BACKGROUND: Laser devices are ubiquitous in everyday operations. These devices
      pose a hazard to the eye and numerous injuries have been documented. However,
      there lies a misunderstanding in the propensity to damage aircrews' eyes during
      an exposure. Patient encounters and article review is presented in hopes to raise
      awareness that aircrew laser exposure at altitude, outside of critical phases of
      flight, is a distraction and not a threat. Also, to propose a change to Air Force
      policy regarding such exposures and further educating flight surgeons. METHODS:
      An electronic medical record (EMR) search at a deployed clinic was performed from
      July 2016 through Jan 2017. The "reason for visit" column was perused for any
      reference to the eye and laser exposure. Subsequently, the patient encounters
      were scrutinized specifically for eye injury, optometry visit, color of laser,
      and suspension of flight duties. All members were military aircrew spanning
      loadmasters, boom operators, and pilots. No protective lenses or other forms of
      optics were employed at time of exposure. RESULTS: There were 21 encounters
      reviewed; 1 patient was seen twice due to 2 separate instances. Of the
      encounters, 14 were green lasers, 6 did not comment, and 1 indicated white. Zero
      acute injuries were discovered. DISCUSSION: Patients were needlessly sent for
      further examination and prohibited from performing their duties. Following
      military patient encounters and civilian literature regarding laser injury, the
      evidence highly supports the hypothesis that hand-held laser exposure in flight
      from a ground base does not engender eye injury. More emphasis should be placed
      on recognizing the laser threat as a distraction or disruption to critical phases
      of flight, and a policy change may be in order for the USAF laser exposure
      guide.Dietrich KC. Aircrew and handheld laser exposure. Aerosp Med Hum Perform.
      2017; 88(11):1040-1042.

PMID- 29046181
TI  - Instrument Failure, Stress, and Spatial Disorientation Leading to a Fatal Crash
      With a Large Aircraft.
AB  - BACKGROUND: An aircraft's orientation relative to the ground cannot be perceived
      via the sense of balance or the somatosensory system. When devoid of external
      visual references, the pilot must rely on instruments. A sudden unexpected
      instrument indication is a challenge to the pilot, who might have to question the
      instrument instead of responding with the controls. In this case report we
      analyze, from a human-factors perspective, how a limited instrument failure led
      to a fatal accident. CASE REPORT: During straight-ahead level flight in darkness,
      at 33,000 ft, the commander of a civil cargo airplane was suddenly confronted by
      an erroneous pitch-up indication on his primary flight display. He responded by
      pushing the control column forward, making a bunt maneuver with reduced/negative
      Gz during approximately 15 s. The pilots did not communicate rationally or cross
      check instruments. Recordings of elevator and aileron positions suggest that the
      commander made intense efforts to correct for several extreme and erroneous roll
      and pitch indications. Gz displayed an increasing trend with rapid fluctuations
      and peaks of approximately 3 G. After 50 s the aircraft entered a turn with
      decreasing radius and finally hit the ground in an inverted attitude. DISCUSSION:
      A precipitate maneuvring response can, even if occurring in a large aircraft at
      high altitude, result in a seemingly inexorable course of events, ending with a
      crash. In the present case both pilots were probably incapacitated by acute
      psychological stress and spatial disorientation. Intense variations in Gz may
      have impaired the copilot's reading of the functioning primary flight
      display.Tribukait A, Eiken O. Instrument failure, stress, and spatial
      disorientation leading to a fatal crash with a large aircraft. Aerosp Med Hum
      Perform. 2017; 88(11):1043-1048.

PMID- 29046182
TI  - You're the Flight Surgeon.
AB  - Speakman RO. You're the flight surgeon: hypertension, when it doesn't add up.
      Aerosp Med Hum Perform. 2017; 88(11):1049-1052.

PMID- 29046184
TI  - Erratum.

PMID- 29046183
TI  - You're the Flight Surgeon.
AB  - Pelligra S. You're the flight surgeon: decompression illness following altitude
      chamber exposure. Aerosp Med Hum Perform. 2017; 88(11):1052-1055.

PMID- 29046185
TI  - The Medilab Mir Module.

PMID- 29046186
TI  - Statement of Ownership, Management, and Circulation.

PMID- 29046187
TI  - This Month in Aerospace Medicine History.

PMID- 29046188
TI  - Association of imbalance of effector T cells and regulatory cells with the
      severity of asthma and allergic rhinitis in children.
AB  - PURPOSE: This study investigated the frequency and absolute numbers of different
      subsets of peripheral blood cells, including CD4+ T cells and CD19+ interleukin
      (IL) 10+ B regulatory cells (Breg) and their potential association with clinical
      laboratory measurements in children diagnosed with simple asthma or asthma plus
      allergic rhinitis (AR). METHOD: The frequency and numbers of peripheral blood
      CD4+ interferon (IFN) gamma+ T-helper (Th) type 1, CD4+ IL-4+ Th2, CD4+ IL-17A+
      Th17, CD4+CD25+ Forkhead Box P3+ regulatory T cells (Treg) and CD19+ IL-10+ Bregs
      in 22 children with asthma, 17 children with asthma and AR, and 25 healthy
      controls were determined by flow cytometry. The levels of serum cytokines were
      determined by enzyme-linked immunosorbent assay. RESULTS: In comparison with
      healthy controls, patients with asthma alone had significantly increased numbers
      of Th1, Th2, and Th17 cells, and their cytokines but decreased numbers of Tregs
      and Bregs, and the cytokines IL-10 and transforming growth factor beta 1. This
      imbalance between effector and regulatory cells and their cytokines further
      increased in patients with asthma and AR. The ratios of percentage effector T
      cells (Th1 + Th2 + Th17) to regulatory cells (Treg + Breg) were positively
      correlated with fractional exhaled nitric oxide but negatively correlated with
      forced expiratory volume in 1 second in patients with asthma or asthma plus AR.
      CONCLUSION: The imbalance of effector T cells and regulatory cells contributed to
      the pathogenesis of airway inflammation of asthma and AR in children.

PMID- 29046189
TI  - High adherence to subcutaneous immunotherapy in a real-life study from a large
      tertiary medical center.
AB  - BACKGROUND: Studies on real-life adherence to subcutaneous allergen immunotherapy
      (SCIT) for respiratory allergy are scarce. The aim of this study was to evaluate
      adherence to SCIT. METHODS: The patients prescribed SCIT for allergic rhinitis
      and/or asthma in 2009-2011 were contacted in 2014 and asked whether they
      completed at least the 3 years of SCIT and/or whether they suspended the
      treatment for at least 2 months. The Total Symptom Score-6, visual analog scale
      (VAS), asthma control test (ACT), medication scores, quality of life (QoL)
      scores, and immunotherapy satisfaction scores with VAS obtained before the
      initiation of SCIT in the first year and at the end of SCIT were compared.
      RESULTS: A total of 204 patients (136 female [66.7%]; mean age, 38.83 +/- 12.02
      years) were included; 73% (149/204) were both compliant and persistent; 14%
      (29/204) were only persistent; and, overall, 87.3% (178/204) were considered
      adherent. Adherence was more frequent in female patients (95% CI, 62.3-76.3%; p =
      0.018). Medication, symptom, ACT, and QoL scores in the first year and at the end
      of the treatment were significantly lower than the initial scores, and the
      immunotherapy satisfaction scores at the end of treatment were higher than the
      scores in the first year in the patients who were adherent (p < 0.001 for each
      score). CONCLUSION: The adherence rate to SCIT in our study was relatively high,
      in contrast to previous real-life data. Results of our study indicated that a
      close relationship between allergists and their patients during SCIT and the
      follow-up period in the same center improved the outcome of SCIT.

PMID- 29046190
TI  - Hereditary angioneurotic edema ... a disease has been described.

PMID- 29046191
TI  - Interleukin 31 and skin diseases: A systematic review.
AB  - BACKGROUND: Although the pathophysiology of pruritus has been extensively studied
      in recent years, with many resultant advancements, management of pruritus is
      still enigmatic, particularly in chronic cutaneous diseases, such as atopic
      dermatitis, chronic urticaria, allergic contact dermatitis, cutaneous T-cell
      lymphoma, and uremic pruritus. The recent finding of the involvement of
      interleukin (IL) 31 in the pathogenesis of chronic pruritus has provided a novel
      approach to the management of chronic inflammatory skin disorders. The present
      report provided an in-depth overview of the role of IL-31 in chronic skin
      diseases and the possible diagnostic and therapeutic applications in the
      management of these diseases. METHODS: A systematic review of IL-31 was conducted
      by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. RESULTS: A review of a total of 45 published research articles
      revealed that the majority of these articles focused on the role of IL-31 in
      causation of pruritus and in the worsening of the disease in atopic dermatitis.
      Other publications examined interleukin in other pruritic diseases (cutaneous T
      cell lymphoma, uremic pruritus, allergic contact dermatitis, chronic urticaria).
      In almost every disease, IL-31 levels were reported to be correlated with the
      pathology and often with pruritus. The cutaneous injection of IL-31 resulted in a
      long-lasting itching sensation, and the use of monoclonal antibodies that
      targeted IL-31 led to a reduction in pruritus. CONCLUSION: The use of monoclonal
      antibodies against mediators involved in the pathogenesis of chronic skin
      diseases has shown promising results. Antibodies that target IL-31, in
      particular, its receptor A, showed interesting results in atopic dermatitis and
      decreased pruritus. In subsequent years, the use of these new therapeutic
      strategies could change the scenario of pruritic skin diseases. However, further
      studies are needed to more rigorously examine the effects of IL-31 cascade
      blockage in different chronic skin diseases and to confirm efficacy and the
      safety of these new therapeutic approaches.

PMID- 29046192
TI  - Management of adverse reactions to biologic agents.
AB  - Hypersensitivity reactions (HSR) to targeted biologic agents present as immediate
      reactions during infusion or as delayed reactions (after one or more exposures).
      The new classification includes phenotypes, endotypes, and biomarkers. Phenotypes
      include immediate type I (immunoglobulin E [IgE] or non-IgE mediated), cytokine
      release, mixed (type I/cytokine), and immune complexes type III (IgG mediated)
      reactions as well as delayed type IV reactions. Endotypes include IgE or non-IgE
      mediated mast cells/basophils activation with elevated serum tryptase and T cells
      values as well as macrophages, which lead to cytokine production, e.g.,
      interleukin 6. A skin test is a valuable tool in evaluating HSRs to biologics;
      however, its predictive value depends on the type of reaction and the monoclonal
      antibody. Desensitization is a new approach to safely reintroduce biologics when
      they are first-line therapies, and it is available for immediate and delayed
      reactions. Research is needed to further understand the mechanisms of reactions
      to monoclonal antibodies and their management.

PMID- 29046193
TI  - Health-related quality of life in Danish children with hereditary angioedema.
AB  - BACKGROUND: The potentially life-threatening disease hereditary angioedema with
      C1-inhibitor deficiency (C1-INH-HAE) can have considerable impact on the health
      related quality of life (HRQoL) in adult patients. Half the patients with C1-INH
      HAE develop symptoms before the age of 10 years. However, the HRQoL in children
      with C1-INH-HAE is almost unexplored. OBJECTIVE: To investigate HRQoL in Danish
      children with C1-INH-HAE, including possible correlations to disease severity and
      attack frequency. METHODS: All Danish children ages 2-18 years with C1-INH-HAE
      were invited to complete questionnaires regarding HRQoL; 14 (93%) agreed. Child
      self-report forms were used for children ages >=5 years. The instruments used
      were the PedsQL (Child Self-Report and Parent Proxy-Report forms); the Children's
      Dermatology Life Quality Index; a nonvalidated, disease-specific quality-of-life
      questionnaire; and two visual analog scales that rated general health. RESULTS:
      The HRQoL scores in our study were comparable with the normal scores for healthy
      children and better than the scores in the only other study dedicated to HRQoL in
      children. Children with recent attacks had lower scores, whereas HRQoL scores
      were not correlated to overall disease severity or age. Surprisingly, home
      therapy was associated with lower HRQoL; however, home therapy was also
      correlated to a higher overall severity score and more frequent attacks. There
      was a strong child-parent agreement in the PedsQL forms, but scores were
      independent of whether the child had a family history of C1-INH-HAE or sporadic
      C1-INH-HAE and whether the parent completing the Parent Proxy-Report form carried
      the disease. CONCLUSION: Overall, the children assessed on average had a normal
      HRQoL and better than those with other common skin disorders. However, according
      to our findings, health care providers should be especially attentive to HRQoL
      when children with C1-INH-HAE become symptomatic.

PMID- 29046195
TI  - For the Patient.

PMID- 29046194
TI  - The role of intravenous access during oral food challenges in food protein
      induced enterocolitis syndrome.
AB  - BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non
      immunoglobulin E mediated food hypersensitivity syndrome characterized by profuse
      vomiting and diarrhea, which leads to lethargy, dehydration, and hypotension.
      Given the potential severity of reactions, resolution of FPIES is confirmed via
      oral food challenge (OFC) during which intravenous (IV) access is recommended to
      facilitate IV fluids (IVF) and steroid therapy. Risk factors for IV treatment are
      not well characterized. OBJECTIVES: The objectives of this study were to analyze
      predictors for IV treatment during OFC in patients with FPIES. METHODS: A
      retrospective chart review was conducted of patients with The International
      Classification of Diseases, Ninth Revision codes 558.3 and 558.9, and with OFC
      who were seen in an allergy and immunology clinic from January 2000 to October
      2015. OFC reaction severity was scored (1, mild; 2, moderate; 3, severe), and
      demographics, IV treatment frequency, and OFC outcomes were evaluated. The Fisher
      exact test and Wilcoxon rank sum test statistical analyses were performed.
      RESULTS: Of 184 patients, 28 met inclusion criteria, with 39 OFCs performed. The
      median age of onset of FPIES was 6 months. The median age at OFC was 2.6 years.
      This was 2.2 years (range, 0.3-8.5 years) from symptom onset. Of 39 OFCs, IV
      treatment, including IVF and/or steroids, was required in only 7.7%. Thirty-eight
      OFCs (97.4%) were of equal or lesser severity than historical reactions. The
      median severity of presenting reaction (3[IV+]:1[IV-]; p = 0.05) was greater in
      those who required IV treatment. OFCs with IV treatment were in younger patients
      (15 months [IV+]:32 months [IV-]; p = 0.039) who underwent OFCs earlier relative
      to the time of diagnosis (8 months [IV+]:28 months [IV-]); p = 0.018).
      CONCLUSION: Although FPIES can potentially elicit severe symptomatology, the
      patients most commonly experienced only vomiting and diarrhea, which often
      resolved with minimal treatment. Reactions generally did not worsen over time.
      Fewer than 10% of the patients challenged required IV treatment, all were young
      and with severe FPIES. It is reasonable to consider age and length of time from
      historical reactions when evaluating the necessity of IV placement in patients
      undergoing FPIES OFC.

PMID- 29046196
TI  - [Disaster response plans in the neonatal intensive care unit].
AB  - Newborns in the neonatal intensive care unit (NICU) are highly vulnerable in
      disasters due to their need for specialized and highly technical support. It is
      strongly encouraged to prepare for the most likely disaster scenarios for the
      NICU. During a disaster, neonatal care providers should maintain situational
      awareness for decision-making, including available equipment, medication, and
      staffing. Neonatal care providers also should consider the ethical issues and the
      psychosocial needs of the families and neonatal care staff.

PMID- 29046197
TI  - [Prospective study of ketogenic diet in treatment of children with global
      developmental delay].
AB  - OBJECTIVE: To study the effect of ketogenic diet (KD) on neurobehavioral
      development, emotional and social behaviors, and life ability in children with
      global developmental delay (GDD). METHODS: A prospective case-control study was
      performed for hospitalized children with GDD, who were randomly divided into KD
      treatment group (n=40) and conventional treatment group (n=37). The children in
      both groups were given comprehensive rehabilitation training, and those in the KD
      treatment group were given modified Atkins diet in addition to the comprehensive
      rehabilitation training. The children in both groups were assessed with the
      Gesell Developmental Scale, Chinese version of Urban Infant-Toddler Social and
      Emotional Assessment (CITSEA)/Achenbach Child Behavior Checklist (CBCL), and
      Infants-Junior High School Students' Social Life Abilities Scale (S-M scale)
      before treatment and after 3, 6, and 9 months of treatment. The two groups were
      compared in terms of the improvements in neurobehavioral development, emotional
      and social behaviors, and social life ability. RESULTS: After 3, 6, and 9 months
      of treatment, the KD treatment group had significantly greater improvements in
      the scores of the adaptive, fine motor, and language quotients of the Gesell
      Developmental Scale compared with the conventional treatment group (P<0.05); the
      KD treatment group had significantly greater improvements in CITSEA/CBCL scores
      than the conventional treatment group (P<0.05). The KD treatment group had a
      greater improvement in the score of the S-M scale after 9 months of treatment
      (P<0.05). During the KD treatment, 6 children experienced diarrhea and 1
      experienced mild urinary stones. CONCLUSIONS: KD can improve the neurobehavioral
      development and behavioral and emotional behaviors in children with GDD, and it
      has few adverse effects.

PMID- 29046198
TI  - [Immunological mechanism of prednisone in the treatment of infantile spasm].
AB  - OBJECTIVE: To investigate the immunological mechanism of prednisone in the
      treatment of infantile spasm (IS) by evaluating the immune function of IS
      children before and after treatment. METHODS: Thirty children with IS were
      enrolled as IS group. Thirty healthy infants who underwent physical examination
      were enrolled as healthy control group. Fasting venous blood was collected for
      both groups before and after prednisone treatment. Chemiluminescence was used to
      measure serum levels of interleukin-1B (IL-1B), interleukin-2R (IL-2R),
      interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF
      alpha). Immunoturbidimetric assay was used to measure serum levels of
      immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG). Flow
      cytometry was used to measure the percentages of T lymphocyte subsets (CD3+,
      CD4+, and CD8+). The clinical outcome and electroencephalographic findings were
      evaluated for all IS children after prednisone treatment. RESULTS: The IS group
      had significantly higher serum levels of IL-2R, IL-8, and TNF-alpha than the
      healthy control group before treatment (P<0.05). The mean number of daily ictal
      clusters was positively correlated with the levels of IL-2R, IL-8, and TNF-alpha
      in IS children, the mean number of total daily seizures was positively correlated
      with IL-8 level, and any two indices out of IL-2R, IL-8, and TNF-alpha were
      positively correlated with each other (P<0.05). Among the 30 IS children treated
      with prednisone, 19 achieved seizure control; electroencephalography showed that
      18 children achieved complete remission of hyperarrhythmia. After treatment, the
      IS group had significant reductions in the numbers of daily ictal clusters and
      total daily seizures, significant improvement in developmental quotient (P<0.05),
      and significant reductions in serum levels of IL-2R, L-8, and TNF-alpha, the
      percentage of CD4+ T lymphocytes, and CD4+/CD8+ ratio (P<0.05), as well as a
      significant increase in the percentage of CD8+ T lymphocytes (P<0.05).
      CONCLUSIONS: IS children have immune dysfunction. Prednisone can control seizures
      in IS children, possibly by regulating and improving immune dysfunction.

PMID- 29046199
TI  - [Association between serum 25(OH)D levels at birth and bronchopulmonary dysplasia
      in preterm infants].
AB  - OBJECTIVE: To assess the association between serum 25-hydroxyvitamin D [25(OH)D]
      levels at birth and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS:
      This study recruited preterm infants with gestational age of below 34 weeks who
      were born between January 2014 and December 2016. These preterm infants were
      classified into two groups: BPD and control. The association between serum
      25(OH)D levels at birth and BPD was analyzed. RESULTS: Serum 25(OH)D levels in
      the BPD group was significantly lower than those in the control group [(37+/-17
      nmol/L vs 47+/-20 nmol/L; P<0.05), and the rate of vitamin D deficiency was
      significantly higher than those in the control group (90.2% vs 74.0%; P<0.05).
      The level of serum 25(OH)D was negatively correlated with the incidence of BPD
      (r=-0.201, P=0.001). CONCLUSIONS: Vitamin D deficiency at birth may be associated
      with BPD in preterm infants, but need to be further studied by multivariate
      analysis.

PMID- 29046200
TI  - [Readmission of children with bronchopulmonary dysplasia in the first 2 years of
      life: a clinical analysis of 121 cases].
AB  - OBJECTIVE: To investigate the clinical features of readmitted children with
      bronchopulmonary dysplasia (BPD) in the first 2 years of life. METHODS: A
      retrospective analysis was performed for the clinical data of 242 children with
      BPD who were readmitted due to recurrent lower respiratory tract infection (LRTI)
      in the first 2 years of life. RESULTS: Among all the 242 children with BPD,
      115(47.5%) had wheezing, and the children aged 1-2 years had a significantly
      higher incidence rate of wheezing than those aged less than 1 year (P<0.05).
      Chest imaging was performed for 193 children, among whom 31 (16.1%) had
      hyperlucent areas. Pulmonary function examination showed that the BPD children
      had significantly lower TV/kg, TPEF/TE, VPEF/VE, TEF50 and TEF75, and
      significantly higher respiratory rate than the controls without respiratory
      disease (P<0.05). Bronchoscopy was performed for 28 children, among whom 21 (75%)
      had airway dysplasia. All the 242 children used inhaled corticosteroids (ICS) and
      experienced no treatment-related adverse reactions. Six children were given
      intravenous infusion of human umbilical cord blood mesenchymal stem cells (hUCB
      MSCs) and experienced no infusion-related events or adverse reactions, among whom
      one child successfully stopped oxygen therapy. CONCLUSIONS: The incidence rate of
      wheezing increases with the increase in age in children with BPD who are
      readmitted due to LRTI. Pulmonary function examination shows small airway
      obstruction, reduced expiratory flow rate in case of low lung capacity, and
      increased respiratory rate, and most children have airway dysplasia. ICS can be
      used to inhibit inflammatory response in the acute stage. Infusion of hUCB-MSCs
      is safe and feasible and may bring some benefits to the recovery from BPD.

PMID- 29046201
TI  - [A clinical analysis of 101 infants with plagiocephaly].
AB  - OBJECTIVE: To investigate the possible causes of plagiocephaly in infants and the
      therapeutic effect of postural correction training on plagiocephaly. METHODS: A
      total of 101 infants who were diagnosed with plagiocephaly were enrolled.
      According to the age at diagnosis, these infants were divided into 1-4 month
      group (31 infants), 5-8 month group (40 infants), and 9-12 month group (30
      infants). The possible causes of plagiocephaly were analyzed in three groups. The
      cranial vault asymmetry index (CVAI) before and after postural correction
      training was compared in three groups. RESULTS: Of the 101 infants, 89 (88.1%)
      had a sleeping posture in the supine position, and there was no significant
      difference in the percentage of infants with such posture between the three
      groups. Compared with the 5-8 month group and the 9-12 month group, the 1-4 month
      group had significantly higher rate of preterm birth, incidence rate of adverse
      perinatal factors, and incidence rate of congenital muscular torticollis. The
      three groups showed a significant decrease in CVAI 3 months after postural
      correction training (P<0.001). Compared with the 5-8 month group and the 9-12
      month group, the 1-4 month group had a significantly greater change in CVAI after
      postural correction training (P<0.001). CONCLUSIONS: The sleeping posture in the
      supine position may be associated with the development of plagiocephaly. Adverse
      perinatal factors, preterm birth, and congenital muscular torticollis as possible
      causes of plagiocephaly are commonly seen in early infancy. Postural correction
      training has a significant effect in improving plagiocephaly, especially in early
      infancy.

PMID- 29046202
TI  - [An investigation of ketoacidosis in children with newly diagnosed type 1
      diabetes].
AB  - OBJECTIVE: To investigate the incidence of diabetic ketoacidosis (DKA) in
      children with newly diagnosed type 1 diabetes. METHODS: A retrospective analysis
      was performed for the clinical data of 224 children with newly diagnosed type 1
      diabetes, and according to the presence or absence of DKA, these children were
      divided into DKA group and non-DKA group, with 112 children in each group. The
      DKA group was further divided into >=5-year group (65 children) and <5-year group
      (47 children), and according to the blood gas parameters, this group was divided
      into mild group (26 children), moderate group (29 children), and severe group (57
      children). The factors influencing the development of DKA were analyzed, as well
      as the clinical and laboratory features of DKA children with different ages.
      RESULTS: The most common symptoms in these 224 children with type 1 diabetes were
      polydipsia (86.2%), polyuria (78.6%), and weight loss (57.1%). Compared with the
      non-DKA group, the DKA group had a significantly higher percentage of children
      who were aged <5 years, who had low family income, or whose parents had an
      educational level of senior high school or below. The DKA group had significantly
      higher levels of random blood glucose and HbA1C and significantly lower levels of
      pH, HCO3-, and C-peptide than the non-DKA group (P<0.05). There was no
      significant difference in the percentage of children with severe DKA between the
      >=5-year group and the <5-year group (P>0.05). Compared with the <5-year group,
      the >=5-year group sufferred from symptoms for a significantly prolonged period,
      and had a significantly lower level of random blood glucose and significantly
      higher levels of HbA1C and C-peptide (P<0.05). CONCLUSIONS: DKA has a high
      incidence rate in children with type 1 diabetes, and the development of DKA is
      associated with age, parents' educational level, and family income.

PMID- 29046203
TI  - [Clinical effect of anti-D immunoglobulin in treatment of childhood immune
      thrombocytopenia: a Meta analysis].
AB  - OBJECTIVE: To investigate the clinical effect and safety of anti-D immunoglobulin
      (anti-D) in the treatment of children with newly diagnosed acute immune
      thrombocytopenia (ITP) through a Meta analysis. METHODS: PubMed, EMBASE, Cohrane
      Library, Ovid, CNKI, and Wanfang Data were searched for randomized controlled
      trials (RCTs) published up to April 2017. Review Manager 5.3 was used for the
      Meta analysis. RESULTS: Seven RCTs were included. The Meta analysis showed that
      after 72 hours and 7 days of treatment, the intravenous immunoglobulin (IVIG)
      group had a significantly higher percentage of children who achieved platelet
      count >20*109/L than the anti-D group (P<0.05). There were no significant
      differences in platelet count after 24 hours, 72 hours, and 7 days of treatment
      between the anti-D (50 MUg/kg) group and the IVIG group (P>0.05), and there were
      also no significant differences in platelet count after 24 hours and 7 days of
      treatment between the 50 MUg/kg and 75 MUg/kg anti-D groups (P>0.05). The anti-D
      group had a significantly greater reduction in the hemoglobin level than the IVIG
      group after treatment, but did not need transfusion. No children in the anti-D
      group or the IVIG group experienced serious adverse reactions. CONCLUSIONS:
      Intravenous injection of anti-D may have a similar effect as IVIG in improving
      platelet count in children with acute ITP, but it may be slightly inferior to
      IVIG in the rate of platelet increase after treatment. The anti-D dose of 50
      MUg/kg may have a similar effect as 75 MUg/kg. The recommended dose of anti-D for
      treatment of ITP is safe.

PMID- 29046204
TI  - [Clinical features and VPS33B mutations in a family affected by arthrogryposis,
      renal dysfunction, and cholestasis syndrome].
AB  - Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal
      recessive disorder caused by mutations in the VPS33B or VIPAS39 gene. The aim of
      this study was to investigate the clinical features and VPS33B gene mutations of
      an infant with ARC syndrome. A 47-day-old female infant was referred to the
      hospital with the complaint of jaundiced skin and sclera for 45 days and abnormal
      liver function for 39 days. The patient had been managed in different hospitals,
      but the therapeutic effects were unsatisfactory due to undetermined diagnosis.
      Physical examination showed jaundice of the skin and sclera. Systemic skin was
      dry with desquamation in the limbs and trunk. There were no positive signs on
      cardiopulmonary examination. The liver was palpable 2.0 cm under the right
      subcostal margin. The hips and knees were flexed, and the extension was limited,
      with low muscular tone in the four limbs. Biochemical analysis demonstrated
      raised serum total bile acids, bilirubin (predominantly conjugated bilirubin) and
      transaminases, but the gamma-glutamyl transpeptidase level was normal. Routine
      urine test revealed increased glucose as well as red and white blood cells. On
      genetic analysis, the infant was proved to be homologous for a VPS33B mutation
      c.1594C>T(p.R532X). She was definitely diagnosed to have ARC syndrome.
      Symptomatic and supportive therapy was given, but no improvement was observed,
      and the infant finally died at 3 months and 29 days of life.

PMID- 29046205
TI  - [Clinical phenotype and genetic analysis of MED13L syndrome].
AB  - A boy aged 4 years and 2 months was found to have delayed language and motor
      development, instability of gait, poor eye contact, stereotyped behavior, and
      seizure at the age of 3 years. Physical examination showed special facial
      features, including plagiocephaly, blepharoptosis, wide nasal bridge, down-turned
      mouth corners at both sides, and low-set ears. There were only two knuckles at
      the little finger of the left hand. The anteroposterior and lateral films of the
      spine showed scoliosis; echocardiography showed ventricular septal defect; the
      Gesell Developmental Scale showed delayed language development and moderate
      intellectual disability; there were no abnormalities in the karyotype; genome
      wide SNP arrays found a duplication in 12q24.21 region with a size of 1.03 Mb in
      chromosome 12, while this was not seen in his parents. The boy was diagnosed with
      MED13L syndrome. Point mutation, deletion, and duplication in the MED13L gene can
      lead to MED13L syndrome. The patients with different genotypes may have different
      phenotypes. Genome-wide SNP arrays may help with the diagnosis of this disease.

PMID- 29046206
TI  - [Clinical and genetic analyses of a family with atypical nonketotic
      hyperglycinemia caused by compound heterozygous mutations in the GLDC gene].
AB  - Nonketotic hyperglycinemia (NKH) is an autosomal recessive hereditary disease
      caused by a defect in the glycine cleavage system and is classified into typical
      and atypical NKH. Atypical NKH has complex manifestations and is difficult to
      diagnose in clinical practice. This article reports a family of NKH. The parents
      had normal phenotypes, and the older brother and the younger sister developed
      this disease in the neonatal period. The older brother manifested as intractable
      epilepsy, severe spastic diplegia, intellectual disability, an increased level of
      glycine in blood and cerebrospinal fluid, an increased glycine/creatinine ratio
      in urine, and an increased ratio of glycine concentration in cerebrospinal fluid
      and blood. The younger sister manifested as delayed language development, ataxia,
      chorea, mental and behavior disorders induced by pyrexia, hypotonia, an increased
      level of glycine in cerebrospinal fluid, and an increased ratio of glycine
      concentration in cerebrospinal fluid and blood. High-throughput sequencing found
      a maternal missense mutation, c.3006C>G (p.C1002W), and a paternal nonsense
      mutation, c.1256C>G (p.S419X), in the GLDC gene in both patients. These two
      mutations were thought to be pathogenic mutations by a biological software. H293T
      cells transfected with these two mutants of the GLDC gene had a down-regulated
      activity of glycine decarboxylase. NKH has various phenotypes, and high
      throughput sequencing helps to make a confirmed diagnosis. Atypical NKH is
      associated with the downregulated activity of glycine decarboxylase caused by
      gene mutations.

PMID- 29046207
TI  - [Clinical characteristics and GAA gene mutation in children with glycogen storage
      disease type II: an analysis of 3 cases].
AB  - Glycogen storage disease type II (GSD II) is an autosomal recessive disorder
      caused by a deficiency of the lysosomal glycogen-hydrolyzing enzyme acid alpha
      glucosidase (GAA) and can affect multiple systems including the heart and
      skeletal muscle. The aim of this study was to investigate three children with GSD
      II confirmed by GAA gene analysis and to report their clinical characteristics
      and gene mutations. One case was classified as infantile-onset GSD II, and two
      cases as late-onset GSD II. The infantile-onset patient (aged 4 months) showed no
      weight increase and had dyspnea, muscle hypotonia, and increased alanine
      aminotransferase and creatine kinase; echocardiography showed hypertrophic
      cardiomyopathy. The late-onset patients (aged 8 years and 13 years respectively)
      showed persistently elevated liver enzymes; one of them had recurrent respiratory
      tract infection and restrictive ventilation disorder, and the other case showed
      significantly increased creatase but normal electromyographic findings.
      Peripheral blood genetic testing for GAA gene showed six pathogenic mutations in
      the three cases, and the mutations c.2738C>T and c.568C>T had not been reported.
      Therefore, peripheral blood genetic testing for GAA gene is an effective
      diagnostic method.

PMID- 29046208
TI  - [Clinical and genetic study of an infant with Alagille syndrome: identification
      of a novel chromosomal interstitial deletion including JAG1 gene].
AB  - Alagille syndrome (ALGS) is an autosomal dominant disease affecting multiple
      systems including the liver, heart, skeleton, eyes, kidneys and face. This paper
      reports the clinical and genetic features of an infant with this disease. A 3
      month-and-10-day-old female infant was referred to the hospital with jaundiced
      skin and sclera for 3 months. Physical examination revealed wide forehead and
      micromandible. A systolic murmur of grade 3-4/6 was heard between the 2th and 3th
      intercostal spaces on the left side of the sternum. The abdomen was distended,
      and the liver palpable 3 cm under the right subcostal margin with a medium
      texture. Serum biochemistry analysis revealed abnormal liver function indices,
      with markedly elevated bilirubin (predominantly direct bilirubin), total bile
      acids (TBA) and gamma-glutamyl transpeptidase (GGT). Atrial septal defect and
      pulmonary stenosis were detected on echocardiography. Next generation sequencing
      detected entire deletion of the JAG1 gene, and then chromosomal microarray
      analysis revealed a novel interstitial deletion of 3.0 Mb in size on
      chr20p12.3p12.2, involving JAG1 gene. The child had special facial features,
      heart malformations, and cholestasis, and based on the genetic findings, ALGS was
      definitively diagnosed. Thereafter, symptomatic and supportive treatment was
      introduced. Thus far, the infant had been followed up till his age of 11 months.
      The hyperbilirubinemia got improved, but GGT and TBA were persistently elevated,
      and the long-term outcome needs to be observed. This study extended the JAG1
      mutation spectrum, and provided laboratory evidences for the diagnosis and
      treatment of the patient, and for the genetic counseling and prenatal diagnosis
      in the family.

PMID- 29046209
TI  - [Paroxysmal muscle weakness, liver enlargement, and hypoglycemia in a boy].
AB  - A boy aged 11 years was admitted due to intermittent weakness and difficulty in
      walking for 6 years, and hepatomegaly, glycopenia and unconsciousness for 4
      years. The laboratory examinations showed severe metabolic acidosis,
      hypoglycemia, and abnormal liver function. CT scan showed marked liver
      enlargement with fat density shadow. The boy was given fluid infusion, correction
      of acidosis, intravenous injection of glucose, L-carnitine, compound vitamin B,
      and coenzyme Q10, but he was in a persistent coma and it was difficult to correct
      refractory metabolic acidosis and hypoglycemia. The boy died. Blood and urinary
      organic acid screening and gene detection confirmed that the boy had late-onset
      glutaric aciduria type II (GAIIc) caused by electron-transferring-flavoprotein
      dehydrogenase (ETFDH) gene defect. GAIIc is an inherited metabolic disease with a
      low incidence, resulting in a high misdiagnosis rate. GAIIc should be considered
      for children with recurrent weakness or reduced activity endurance, hypoglycemia,
      and marked liver enlargement with abnormal liver function. Urinary organic acid
      analysis and blood tandem mass spectrometry can help with the early diagnosis of
      GAIIc, and ETFDH gene analysis helps to make a confirmed diagnosis.

PMID- 29046210
TI  - [Diffuse alveolar hemorrhage in 4 girls].
AB  - This article reports 4 girls with clinical manifestations of recurrent cough and
      anemia. The age of onset was less than 4 years, and three of them had shortness
      of breath. None of them had acute hemoptysis. All the girls had positive results
      of hemosiderin test for bronchoalveolar lavage fluid. As for imaging examination,
      3 patients had ground-glass opacity, and 1 had interstitial change. Three girls
      were given the treatment for idiopathic pulmonary hemosiderosis and had no
      response. Selective bronchial arteriography was performed for the 4 girls and
      found bronchial artery to pulmonary circulation shunt (BPS). After they were
      diagnosed with BPS, they were given transcatheter embolization. The girls were
      followed up for half a year after surgery, and none of them was readmitted due to
      "cough and anemia". BPS manifests as abnormal shunt between the bronchial artery
      and the pulmonary artery/vein and has unknown causes. It is rare in children and
      should be considered for children who were thought to have idiopathic pulmonary
      hemosiderosis and had poor response to corticosteroid therapy.

PMID- 29046211
TI  - [Application of extracorporeal membrane oxygenation in 4 critically in neonates].

PMID- 29046212
TI  - [Research advances in hereditary epilepsy and precision drug therapy].
AB  - Epilepsy is a common nervous system disease. It has been found that the
      pathogenesis of epilepsy is associated mutations in various genes, including
      genes encoding voltage-dependent ion channel, genes encoding ligand-gated ion
      channel, and solute carrier family genes. Different types of epilepsy caused by
      different mutations have different responses to drugs, and therefore, diagnosis
      and medication guidance based on genes are new thoughts for developing therapies.
      With the application of next-generation sequencing technology, more and more
      genes will be determined, which helps to further study the pathogenic mechanism
      of mutant genes and provides a basis for precision drug therapy for epilepsy.

PMID- 29046213
TI  - [Changes in blood oxygen metabolism indices and their clinical significance in
      children with septic shock].
AB  - The key to the treatment of septic shock is to provide adequate oxygen supply and
      improve tissue perfusion. Lactate and central venous oxygen saturation (ScvO2)
      are commonly used as the indices of oxygen metabolism, but tissue hypoxia may
      still exist even when lactate and ScvO2 are within the normal range.
      Arteriovenous difference in carbon dioxide partial pressure (CO2 gap) can
      accurately reflect oxygen delivery when ScvO2 is in the normal range. This
      article reviews the advantages and shortages of lactate, lactate clearance rate,
      ScvO2, and CO2 gap in evaluating tissue hypoxia, in order to provide a reference
      for treatment and severity evaluation of septic shock.

PMID- 29046214
TI  - Motivating the workforce: beyond the 'two-factor' model.
AB  - Objective The aim of the present study was to understand the factors motivating
      health and human services professionals in the workplace, thus adding to the body
      of knowledge associated with employee motivation.Methods Brainstorming research
      was performed on frontline and emerging managers in Tasmanian public sector
      organisations. Coding categories were inductively developed from the data, then
      deductively analysed using Herzberg's two-factor model.Results Communication was
      the most significant factor affecting staff motivation. When described as 'good',
      it was open, honest, appropriate and timely. Emotional factors, including a sense
      of being respected and valued, were also highly regarded. Material resources,
      such as budgets, staffing and physical amenities, were the third most cited
      factor affecting workforce motivation.Conclusions Contrary to most previous
      research, the present study found that some factors - like communication or
      resources - could be a source of satisfaction and dissatisfaction, depending on
      whether they supported the individual and the team. The research method chosen in
      the present study differed from most using the two-factor model in that it did
      not use closed survey questions. The breadth of these results reflects the
      ability to provide a more nuanced response.What is known about the topic?
      Professionals working in health and human services have a high degree of
      authority and autonomy. Increasing staff motivation has the potential to
      positively influence organisational and individual outcomes.What does this paper
      add? This paper provides greater insight into factors increasing staff
      motivation. It also suggests methodological improvements for studies using the
      two-factor model.What are the implications for practitioners? The insights into
      staff motivation may be used by employers to improve outcomes and increase
      workforce satisfaction.

PMID- 29046215
TI  - Prospective surveillance of device-associated health care-associated infection in
      an intensive care unit of a tertiary care hospital in New Delhi, India.
AB  - BACKGROUND: Surveillance of health care-associated infections (HAIs) plays a key
      role in the hospital infection control program and reduction of HAIs. In India,
      most of the surveillance of HAIs is reported from private sector hospitals that
      do not depict the situation of government sector hospitals. Other studies do not
      confirm with the Centers for Disease Control and Prevention's (CDC) National
      Healthcare Safety Network (NHSN) surveillance criterion, or deal with ventilator
      associated pneumonia (VAP) instead of ventilator-associated event (VAE). The aim
      of this study was to identify the incidences of 3 device-associated HAIs (DA
      HAIs) (VAE, central line-associated bloodstream infection [CLABSI], and catheter
      associated urinary tract infection [CAUTI]) by active surveillance using CDC's
      NHSN surveillance criteria and to identify the pathogens associated with these DA
      HAIs. METHODS: This was a prospective surveillance study (January 2015-December
      2016) conducted in an intensive care unit (ICU) of a large, tertiary care,
      government hospital situated in Delhi, India. Targeted surveillance was done as
      per the CDC's NHSN 2016 surveillance criteria. RESULTS: There were 343 patients
      admitted to the ICU that were included in the study. The surveillance data was
      reported over 3,755 patient days. A DA-HAIs attack rate of 20.1 per 100
      admissions and incidence of 18.3 per 1,000 patient days was observed. The
      duration of use for each device for patients with DA-HAIs was significantly
      longer than for patients without DA-HAIs. The device utilization ratios of
      central line, ventilator, and urinary catheters were 0.57, 0.85, and 0.72,
      respectively. The crude excess length of stay for patients with DA-HAI was 13
      days, and crude excess mortality rate was 11.8%. VAE, CLABSI, and CAUTI rates
      were 11.8, 7.4, and 9.7 per 1,000 device days, respectively. Among 69 DA-HAIs
      reported, pathogens could be identified for 49 DA-HAI cases. Klebsiella spp was
      the most common organism isolated, accounting 28.5% for all DA-HAI cases,
      followed by Enterococcus spp (24.4%). The most common organisms causing VAE,
      CAUTI, and CLABSI were Acinetobacter (6/15, 40%), Enterococcus spp (11/31,
      35.4%), and Candida spp (5/19, 26.3%), respectively. Most of the gram-negative
      organisms were carbapenem resistant; however, none of the isolates were colistin
      resistant. CONCLUSIONS: To reduce the risk of infection in hospitalized patients,
      DA-HAI surveillance is of primary importance because it effectively describes and
      addresses the importance and characteristics of the threatening situation created
      by DA-HAIs. The present surveillance shows high rates of ICU-onset DA-HAIs and
      high resistance patterns of organisms causing HAIs, representing a major risk to
      patient safety.

PMID- 29046216
TI  - Glove: Use for safety or overuse?

PMID- 29046217
TI  - Corrigendum to "Association of obesity with cognitive function and brain
      structure in patients with major depressive disorder" [J. Affect. Disord. 225
      (2018) 188-194].

PMID- 29046218
TI  - Discussion of: "PTSD and surgical residents: Everybody hurts ... sometimes".

PMID- 29046219
TI  - Discussion of: "Venous thromboembolism in common laparoscopic abdominal surgical
      operations".

PMID- 29046220
TI  - Electrocardiographic recognition of right ventricular hypertrophy.
AB  - The electrocardiogram (ECG) is a relatively insensitive tool for the detection of
      right ventricular hypertrophy (RVH), but some criteria have high specificity. The
      recommended ECG screening criteria for RVH are not sufficiently sensitive or
      specific for screening for mild RVH in adults without clinical cardiovascular
      disease. The greatest accuracy of the ECG is in congenital heart disease, with
      intermediate accuracy in acquired heart disease and primary pulmonary
      hypertension in adults.

PMID- 29046221
TI  - Botulinum toxin after stroke: A functional point of view.

PMID- 29046222
TI  - A social network analysis of the goal scoring passing networks of the 2016
      European Football Championships.
AB  - In the current study, social network analysis (SNA) and notational analysis (NA)
      methods were applied to examine the goal scoring passing networks (GSPN) for all
      goals scored at the 2016 European Football Championships. The aim of the study
      was to determine the GSPN characteristics for the overall tournament, between the
      group and knock out stages, and for the successful and unsuccessful teams. The
      study also used degree centrality (DC) metrics as a novel method to determine the
      relative contributions of the pitch locations involved in the GSPN. To determine
      changes in GSPN characteristics as a function of changing score line, the
      analysis considered the match status of the game when goals were scored. There
      were significant differences for SNA metrics as a function of match status, and
      for the DC metrics in the comparison of the different pitch locations. There were
      no differences in the SNA metrics for the GSPN between teams in the group and
      knock out stages, or between the successful and unsuccessful teams. The results
      indicate that the GSPN had low values for network density, cohesion, connections,
      and duration. The networks were direct in terms of pitch zones utilised, where
      85% of the GSPN included passes that were played within zones or progressed
      through the zones towards the goal. SNA and NA metrics were significantly
      different as a function of changing match status. The current study adds to the
      previous research on goal scoring in football, and demonstrates a novel method to
      determine the prominent pitch zones involved in the GSPN. These results have
      implications for match analysis and the coaching process.

PMID- 29046223
TI  - Antibodies to receptors are associated with biomarkers of inflammation and
      myocardial damage in heart failure.
AB  - INTRODUCTION: Naturally occurring antibodies are linked to inflammation, tissue
      injury and apoptosis, processes also linked to heart failure. Associations
      between antibodies, inflammation and myocardial damage, have not been elucidated
      in heart failure. OBJECTIVE: We investigated if 25 antibodies to receptors
      expressed in the cardiovascular system were associated with troponin-T,
      biomarkers of inflammation and clinical measures of disease severity, in patients
      with heart failure. METHODS: Antibodies in sera from patients (n=191) with
      ischemic (n=155) or non-ischemic (n=36) heart failure were measured with full
      receptor sandwich enzyme-linked immunosorbent assays. All patients underwent
      coronary angiography with determination of left ventricular ejection fraction
      (LVEF) and left ventricular end-diastolic pressure (LVEDP). Measured biomarkers
      included troponin-T, C-reactive protein, erythrocyte sedimentation rate,
      fibrinogen and neopterin. RESULTS: Stabilin-1-antibodies correlated with troponin
      T (beta 0.23 p=0.008), soluble endoglin-antibodies with erythrocyte sedimentation
      rate (beta 0.19, p=0.007) and fibrinogen (beta 0.28, p<0.001). Platelet-derived
      growth factor subunit beta-antibodies were associated with neopterin (beta 0.17,
      p=0.002). All antibodies were correlated (R 0.26 to 0.91) and formed 4 principal
      components (PCs). Patients with high CRP and high PC2 had higher NYHA class and
      patients with high troponin-T and high PC1 had lower LVEDP (interactions, all
      p<0.05). CONCLUSION: Antibodies to receptors are correlated and are associated
      with biomarkers of inflammation and myocardial damage, which further modifies
      their association with disease severity in heart failure. Their functional
      activity and immunological function, remain undecided.

PMID- 29046224
TI  - Reprint of: Impact of the corrin framework of vitamin B12 on the electrochemical
      carbon-skeleton rearrangement in comparison to an imine/oxime planar ligand;
      tuning selectivity in 1,2-migration of a functional group by controlling
      electrolysis potential.
AB  - Among the coenzyme B12-dependent enzymes, methylmalonyl-CoA mutase (MMCM)
      catalyzes the carbon-skeleton rearrangement reaction between R-methylmalonyl-CoA
      and succinyl-CoA. Diethyl 2-bromomethyl-2-phenylmalonate, an alkyl bromide
      substrate having two different migrating groups (phenyl and carboxylic ester
      groups) on the beta-carbon, was applied to the electrolysis mediated by a
      hydrophobic vitamin B12 model complex, heptamethyl cobyrinate perchlorate in this
      study. The electrolysis of the substrate at -1.0V vs. Ag-AgCl by light
      irradiation afforded the simple reduced product (diethyl 2-methyl-2
      phenylmalonate) and the phenyl migrated product (diethyl 2-benzyl-2
      phenylmalonate), as well as the electrolysis of the substrate at -1.5V vs. Ag
      AgCl in the dark. The electrolysis of the substrate at -2.0V vs. Ag-AgCl afforded
      the carboxylic ester migrated product (diethyl phenylsuccinate) as the major
      product. The selectivity for the migrating group was successfully tuned by
      controlling the electrolysis potential. We clarified that the cathodic chemistry
      of the Co(III) alkylated heptamethyl cobyrinate is critical for the selectivity
      of the migrating group through mechanistic investigations and comparisons to the
      simple vitamin B12 model complex, an imine/oxime-type cobalt complex.

PMID- 29046225
TI  - Composition and influencing factors of bacterial communities in ballast tank
      sediments: Implications for ballast water and sediment management.
AB  - This study aims to reveal the composition and influencing factors of bacterial
      communities in ballast tank sediments. Nine samples were collected and their 16S
      rRNA gene sequences were analyzed by high-throughput sequencing. The analysis
      results showed the Shannon index in ballast tank sediments was in the range of
      5.27-6.35, which was significantly higher than that in ballast water.
      Acidobacteria, Actinobacteria, Bacteroidetes, Chloroflexi and Proteobacteria were
      the dominant phyla and accounted for approximately 80% of all 16S rRNA gene
      sequences of the samples. Besides, the high contents of sulfate reducing bacteria
      (SRB) and sulfur oxidizing bacteria were detected in sediments, indicating that
      the corrosion of metal caused by SRB might occur in ballast tank. In addition,
      the trace of human fecal bacteria and candidate pathogens were also detected in
      ballast tank sediments, and these undesirable microbes reduced the effect of
      ballast water exchange. Furthermore, C and N had significant effects on the
      bacterial community composition in ballast tank sediments. In conclusion, our
      findings suggest that the proper management and disposal of the ballast tank
      sediments should be considered in order to reduce the negative impact and
      ecological risks related to ballast water and sediments.

PMID- 29046226
TI  - Pertussis toxin IgA testing over-diagnoses recent pertussis infection.
AB  - The importance of pertussis toxin (PT) IgA testing in the diagnosis of recent
      pertussis infection remains unclear. The contribution of PT IgA to the diagnosis
      of recent pertussis was reviewed in two separate analyses. Firstly, an evaluation
      of two new automated assays [DiaSorin Liaison (DL), Italy] for PT IgG and PT IgA
      provided an opportunity to assess the contribution of PT IgA testing to PT IgG
      results. Secondly, a retrospective review of results from the PT IgA assay
      currently in use [Sullivan Nicolaides Pathology (SNP) PT IgA] was performed from
      2013 to 2015 (n=63,474). For both the DL and SNP assays, the combination of PT
      IgG and PT IgA resulted in reduced specificity as compared to PT IgG results
      alone. For DL assays, an algorithm restricting DL PT IgA testing to samples with
      equivocal PT IgG results, demonstrated superior specificity to routinely testing
      both assays. The retrospective review indicated that only a minority of patients
      had a SNP PT IgA response without an accompanying rise in SNP PT IgG. There was
      also evidence of an age-related increase in the prevalence of isolated positive
      SNP PT IgA results which did not appear to be associated with recent pertussis
      infection. In general, PT IgA appears to contribute little diagnostic value to an
      accurate PT IgG assay in a community-based, Australian population. Reflex testing
      of PT IgA in the context of equivocal PT IgG results may be worthwhile if
      laboratory workflow permits.

PMID- 29046227
TI  - A Reply to "Effectiveness of an individually-tailored computerised CBT programme
      (Deprexis) for depression: A meta-analysis" by Twomey and colleagues [Psychiatry
      Res. 256 (2017) 371-377].

PMID- 29046228
TI  - Should we perform in utero MRI on a fetus at increased risk of a brain
      abnormality if ultrasonography is normal or shows non-specific findings?
AB  - There are a number of reasons why a pregnant woman might be considered to have an
      increased risk of carrying a fetus with a brain abnormality, but they fall
      broadly into two groups. First, there may be a relevant family history usually,
      but not always, when a fetus/child from a previous pregnancy has a developmental
      brain abnormality and a clinical geneticist judges that there is a risk of
      recurrence. Second, there may be findings in their current pregnancy that
      increases the risk of the fetus either having a developmental brain abnormality
      or accruing acquired brain pathology. Antenatal ultrasonography remains the
      mainstay of fetal screening and anomaly scanning, but there is now persuasive
      evidence that in utero magnetic resonance imaging should have an important
      supporting role. This is important, as more accurate and more certain diagnoses
      are central to providing parents with accurate information about the likely
      clinical outcome. In pregnancies at increased risk of brain abnormalities, it is
      also important to provide the best quality information that the fetal brain is
      normal to provide reassurance to parents. In this paper, we review the
      proposition that in utero magnetic resonance imaging should be used in
      pregnancies at increased risk of brain abnormalities, even if the consultant-led
      ultrasound examination is normal or showed non-specific findings only.

PMID- 29046229
TI  - Fetal Overnutrition and Adolescent Hepatic Fat Fraction: the Exploring Perinatal
      Outcomes in Children Study.
AB  - OBJECTIVE: To determine if fetal overnutrition resulting from maternal obesity or
      gestational diabetes mellitus (GDM) is associated with increased liver fat during
      adolescence, adjusting for past and current metabolic risk factors. STUDY DESIGN:
      Data come from a historical prospective cohort study (Exploring Perinatal
      Outcomes in Children) of 254 mother-child pairs in Colorado who participated in 2
      research visits at T1 (mean age 10.4, SD = 1.5 years) and at T2 (mean age 16.4,
      SD = 1.5 years), and had complete exposure and outcome data. Multiple linear
      regression was used to evaluate the effects of pre-pregnancy body mass index
      (BMI) and GDM on hepatic fat fraction (HFF) by magnetic resonance imaging at T2.
      RESULTS: Maternal pre-pregnancy obesity (BMI 30+) was significantly associated
      (beta = 1.59, CI = 0.66, 2.52) with increased HFF relative to mothers with normal
      pre-pregnancy weight (BMI <25) independent of maternal GDM and sociodemographic
      factors. Moreover, this association was independent of T2 and T1 metabolic risk
      factors (acanthosis nigricans, BMI, fasting glucose) (beta = 1.03, CI = 0.10,
      1.97). Prenatal GDM exposure was not associated with HFF in either unadjusted or
      adjusted models. CONCLUSIONS: Maternal pre-pregnancy obesity was associated with
      increased HFF in offspring independent of childhood and adolescent adiposity.
      Intervention studies are needed to test the hypothesis that maternal obesity is a
      modifiable risk factor for childhood fatty liver disease.

PMID- 29046230
TI  - Carbon materials derived from waste tires as high-performance anodes in microbial
      fuel cells.
AB  - In this study, carbonized waste tires were directly used as a high-performance
      anode material in microbial fuel cells (MFCs). The effect of the pyrolysis
      temperature used for waste tire carbonization on the current output performance
      was investigated to determine the optimal pyrolysis temperature. Thermal
      gravimetric analysis/differential scanning calorimetry showed that tire
      carbonization started at 200 degrees C and ended at about 500 degrees C; the
      weight loss was about 64%. When used in an MFC, the electrode obtained from waste
      tires carbonized at 800 degrees C gave a current density of 23.1+/-1.4Am-2, which
      is much higher than that achieved with traditional graphite felt anodes (5.5+/
      0.1Am-2). The results of this study will be useful in optimizing the design of
      carbonized waste tire anodes for enhancing MFC performances and will alleviate
      the environmental problems caused by waste tires.

PMID- 29046231
TI  - Influence of different revegetation choices on plant community and soil
      development nine years after initial planting on a reclaimed coal gob pile in the
      Shanxi mining area, China.
AB  - In order to identify suitable pioneer plant species for future revegetation of
      coal gob piles, a field survey was conducted to assess the success of different
      revegetation species and their influence on soil development nine years after
      initial planting on a reclaimed coal gob pile in the Yangquan mining area of
      Shanxi province, China. Data were analyzed using a quantitative classification
      method (TWINSPAN), ordination techniques (DCA and DCCA), Principal Component
      Analysis (PCA) and a geo-accumulation index (Igeo). The results revealed that the
      low levels of soil moisture and available N were the major limiting factors
      affecting plant community development on the coal gob pile, not metal toxicity.
      The plant communities that developed had significantly improved the topsoil (0
      10cm) quality on the reclaimed coal gob pile nine years after initial planting
      (p<0.05), but the degree of improvement varied greatly with different planted
      species. Revegetation types comprised of the planted leguminous species, Medicago
      sativa and Amorpha fruticosa, and the non-leguminous species, Populus tomentosa
      and Salix babylonica had the best ecological restoration effects on the reclaimed
      coal gob pile. Revegetation using these species is therefore recommended for
      future reclamation of abandoned coal gob piles in this region.

PMID- 29046232
TI  - Geomorphic controls on fluvial carbon exports and emissions from upland swamps in
      eastern Australia.
AB  - Temperate Highland Peat Swamps on Sandstone (THPSS) are upland wetlands, similar
      to fens in the Northern Hemisphere and are found at the headwaters of low-order
      streams on the plateaus of Eastern Australia. They are classified as endangered
      ecological communities under State and National legislation. Previous works have
      identified particular geomorphic characteristics that are important to carbon
      storage in these low energy sediment accumulation zones. Changes in the
      geomorphic structure of THPSS, such as channelisation, may have profound
      implications for carbon storage. To assess the effect of channelisation on carbon
      budgets in these ecosystems it is essential to identify and quantify differences
      in carbon export, emissions and stocks of carbon of intact swamps and those that
      have become channelised. We undertook seasonal sampling of the perched swamp
      aquifers and surface waters of two intact swamps and two channelised fills in the
      Blue Mountains of New South Wales, Australia, to investigate differences in
      carbon exports and emissions between the two swamp types. We found that
      channelised fills' mean CO2 emissions were almost four times higher than intact
      swamps with mean CH4 emissions up to five times higher. Annual fluvial carbon
      exports for channelised fills were up to 18 times that of intact swamps.
      Channelised fill exports and emissions can represent up to 2% of the total swamp
      carbon stocks per annum which is 40 times higher than the intact swamps. This
      work clearly demonstrates that changes in geomorphic structure brought about by
      incision and channelisation results in profound changes to the carbon storage
      function of THPSS.

PMID- 29046233
TI  - Association Among Gut Microbes, Intestinal Physiology, and Autism.

PMID- 29046234
TI  - Nonsteroidal anti-inflammatory drugs for postoperative pain control after lumbar
      spine surgery: A meta-analysis of randomized controlled trials.
AB  - STUDY OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) play a role in
      pain relief, especially in postoperative pain caused by inflammation. They have
      demonstrated significant opioid dose-sparing effects, which help in reducing
      postoperative effects and opioid side effects. The objective of this meta
      analysis was to explore the role of NSAIDs in reducing postoperative pain at
      different time intervals and provide reference for medication after lumbar spine
      surgery by a meta-analysis of randomized controlled trials (RCT). DESIGN: A meta
      analysis study of randomized controlled trials. SETTING: Postoperative recovery
      area. PATIENTS: Adult patients who have undergone lumbar spine surgery.
      INTERVENTION: Patients received NSAIDs for pain control after lumbar spine
      surgery. MEASUREMENTS: Standardized mean difference (SMD) and 95%CI were used to
      evaluate the visual analog scale of postoperative pain. MAIN RESULTS: Four
      hundred and eight participants from eight studies were included in this study.
      The difference between the NSAIDs group and placebo is significant in 0-6, 12,
      and 24h groups (overall: SMD=-0.72, 95%CI -0.98 to -0.45; 0-6h: SMD=0.50, 95%CI 
      0.81 to -0.19; 12h: SMD=-1.07, 95%CI -1.45 to -0.70; 24h: SMD=-1.16, 95%CI -1.87
      to -0.45). Heterogeneity and publication bias were observed in the 0-6 and 24h
      groups. CONCLUSION: NSAIDs are effective in postoperative analgesia after lumbar
      spine surgery. The study type, NSAID dose, different surgery types, and analgesic
      type might influence the efficacy of NSAIDs.

PMID- 29046235
TI  - White matter integrity correlates with depressive symptomatology in temporal lobe
      epilepsy.
AB  - RATIONALE: White matter abnormalities occur in both temporal lobe epilepsy (TLE)
      and depression, but there is limited research examining the depression-white
      matter association in depressed individuals with TLE. This study examined the
      relationship between white matter integrity (WMI) and depression including the
      influence of age at seizure onset, in adults with TLE, TLE and depression, and
      depression only. METHODS: Thirty-one adults were in one of three groups: TLE
      without depression (TLE; n=11), TLE with depression (TLE+DEP; n=9), and
      depression without TLE (DEP; n=11). Participants completed structured interviews
      for depression diagnosis and severity. White matter integrity was estimated based
      on fractional anisotropy (FA) calculated in frontotemporolimbic (FTL) and non-FTL
      regions in the JHU DTI atlas. RESULTS: In adults with TLE (n=20), depressive
      symptomology was significantly correlated with FA in non-FTL regions and trended
      toward significance in FTL regions. These associations were found in FTL
      (statistically significant) and non-FTL (trended toward significance) regions in
      participants with childhood seizure onset but not in those with adolescent/adult
      seizure onset. CONCLUSIONS: Current results suggest that WMI, within FTL and non
      FTL regions, are associated with depressive symptomology in adults with TLE. This
      association may be most notable in those with childhood-onset epilepsy. These
      findings could have important implications for the conceptualization and clinical
      care of neuropsychiatric comorbidities in TLE.

PMID- 29046237
TI  - Pediatric Temporomandibular Joint Disorders.

PMID- 29046236
TI  - Interactions of TRAF6 and NLRX1 gene polymorphisms with environmental factors on
      the susceptibility of type 2 diabetes mellitus vascular complications in a
      southern Han Chinese population.
AB  - AIMS: To evaluate the effects of TRAF6 and NLRX1 polymorphisms and their
      interactions with environmental factors on the susceptibility of type 2 diabetes
      mellitus (T2DM) vascular complications in a southern Han Chinese population.
      METHODS: Five single nucleotide polymorphisms (SNPs) were genotyped in a case
      control study to estimate risk factors of T2DM vascular complications. Gene-gene
      and gene-environment interactions and haplotype associations were also estimated.
      RESULTS: The CA genotype of the NLRX1 rs4245191 was identified as a risk factor
      for T2DM macrovascular complications and diabetic cerebral infarction (OR=2.88,
      95% CI=1.15-7.22, P=0.024; OR=4.00, 95% CI=1.04-15.38, P=0.043, respectively). A
      significantly lower T allele frequency in the TRAF6 rs16928973 was observed in
      T2DM patients with both microvascular and macrovascular complications compared
      with patients without any complication under the allelic model (T vs. C: OR=0.36,
      95% CI=0.14-0.98, P=0.038). No significant differences in haplotypes, gene-gene
      interactions and gene-environment interactions were observed among T2DM vascular
      subgroup patients. CONCLUSIONS: Our study provides evidence that the NLRX1
      rs4245191 polymorphisms influence the risk of T2DM macrovascular complications
      and diabetic cerebral infarction.

PMID- 29046238
TI  - 1,3,5-Triazines: A promising scaffold for anticancer drugs development.
AB  - This review covering literature reports from the beginning of this century to
      2016 describes the synthetic pathways, the antitumor activity, the structure
      activity relationship and, whenever reported, the possible mechanism of action of
      1,3,5-triazine derivatives as well as of their hetero-fused compounds. Many 1,3,5
      triazine derivatives, both uncondensed and hetero-fused, have shown remarkable
      antitumor activities and some of them reached clinical development.

PMID- 29046239
TI  - Increased Peak Wall Stress, but Not Maximum Diameter, Is Associated with
      Symptomatic Abdominal Aortic Aneurysm.
AB  - OBJECTIVE: Maximum diameter (MD) is the established rupture predictor for
      abdominal aortic aneurysm (AAA). However, biomechanical markers from finite
      element analysis (FEA) could be more accurate predictors for these patients. In
      this study, the association between peak wall stress (PWS) and MD with symptoms
      of AAA was evaluated. METHODS: Patients diagnosed with infrarenal non-ruptured
      AAA at the centre between 2009 and 2015 were included. Clinical data,
      morphological variables (including MD), and the biomechanical variables PWS and
      diameter normalised PWS (dnPWS) in symptomatic (sAAA) and asymptomatic AAA
      patients (aAAA) were included. RESULTS: A total of 170 patients were analysed,
      153 aAAA and 17 sAAA. MD was significantly greater in sAAA patients than in aAAA
      patients (70.4 mm, 95% CI 66.4-86.0 vs. 59.1 mm, 95% CI 53.7-67.8, respectively;
      p = .002). PWS was also significantly higher in the sAAA group (324.6 kPa, 95% CI
      217.4-399.5 vs. 199.2 kPa, 95% CI 165.6-239.5; p < .01). No differences in MD
      were found in patients with an AAA >= 65 mm (43 aAAA and 14 sAAA); however, both
      PWS (327.4 kPa, 95% CI 239.0-473.3 vs. 229.4 kPa, 95% CI 210.0 to 289.4; p =
      .020) and dnPWS (4.3, 95% CI 3.17-4.67 vs. 3.03, 95% CI 2.8-3.49; p = .004) were
      higher in sAAA than in aAAA. CONCLUSIONS: This study suggests that MD and the
      biomechanical parameters obtained by finite element analysis are greater in sAAA
      than in aAAA. However, considering patients with MD >= 65 mm alone, only PWS, and
      particularly dnPWS, were able to differentiate sAAA from aAAA.

PMID- 29046240
TI  - Comparison of temporomandibular joint and ramus morphology between class II and
      class III cases before and after bi-maxillary osteotomy.
AB  - PURPOSE: The purpose of this study was to compare changes in temporomandibular
      joint (TMJ) and ramus morphology between class II and III cases before and after
      sagittal split ramus osteotomy (SSRO) and Le Fort I osteotomy. MATERIALS AND
      METHODS: The subjects were 39 patients (78 sides) who underwent bi-maxillary
      surgery. They consisted of 2 groups (18 class II cases and 21 class III cases),
      and were selected randomly from among patients who underwent surgery between 2012
      and 2016. The TMJ disc tissue and joint effusion were assessed by magnetic
      resonance imaging (MRI) and the TMJ space, condylar height, ramus height, ramus
      inclination and condylar square were assessed by computed tomography (CT), pre-
      and post-operatively. RESULTS: The number of joints with anterior disc
      displacement in class II was significantly higher than that in class III (p <
      0.0001). However, there were no significant differences between the two classes
      regarding ratio of joint symptoms and ratio of joint effusion pre- and post
      operatively. Class II was significantly better than class III regarding reduction
      ratio of condylar height (p < 0.0001) and square (p = 0.0005). CONCLUSION: The
      study findings suggest that condylar morphology could change in both class II and
      III after bi-maxillary surgery. The findings of the numerical analysis also
      demonstrated that reduction of condylar volume occurred frequently in class II,
      although TMJ disc position classification did not change significantly, as
      previously reported.

PMID- 29046241
TI  - Natural variation of the zygomaticomaxillary complex symmetry in normal
      individuals.
AB  - OBJECTIVE: The study aim was to investigate variations in the symmetry of the
      zygomaticomaxillary complex (ZMC) in normal individuals. METHOD: Computed
      tomography datasets of 200 individuals without facial fractures were analyzed
      using a validated three-dimensional analysis technique. The absolute average
      distance (AD) and 90th percentile distance (NPD) were calculated, representing
      respectively the overall and maximum symmetry between bilateral ZMCs. RESULTS:
      The mean AD and NPD of the total study group was 0.9 +/- 0.3 mm (95% CI 0.3-2.3)
      and 1.7 +/- 0.5 mm (95% CI 0.5-3.9), respectively. The mean AD and NPD in males
      were 1.0 +/- 0.3 mm (95% CI 0.28-2.34) and 1.9 +/- 0.5 mm (95% CI 0.5-3.9) versus
      0.8 +/- 0.3 mm (95% CI 0.4-1.7) and 1.6 +/- 0.5 mm (95% CI 0.8-2.9),
      respectively, for females. A statistically significant difference between male
      and female was found for both AD and NPD (p < 0.01). The male population <40
      years had a mean AD and NPD of 1.0 +/- 0.3 mm and 1.8 +/- 0.5 mm, which was not
      statistically significant when compared with males >40 years. CONCLUSION: The
      naturally occurring anatomic variation in ZMC symmetry described in this study is
      proposed as a benchmark for evaluating the amount of preoperative displacement
      and postoperative reduction of ZMC in trauma cases.

PMID- 29046242
TI  - Preoperative corrections are required for planning of patient-specific
      instrumentation in total knee arthroplasty.
AB  - BACKGROUND: Patient-specific instrumentation (PSI) is attracting attention as a
      mechanical method of ensuring the accuracy of osteotomy during total knee
      arthroplasty (TKA). Few studies have focused on preoperative plans; thus, it is
      unclear how often initial plans have to be corrected preoperatively and
      intraoperatively. We investigated the frequency of corrections, the accuracy of
      intraoperative osteotomy, and postoperative alignment. METHODS: We analyzed 45
      knees of 40 patients who underwent TKA using magnetic resonance imaging (MRI)
      based PSI. We evaluated the frequency of corrections to preoperative plans and
      intraoperative corrections for each part. We also evaluated osteotomy error,
      defined as the difference between the planned and actual thickness of resected
      bone. Hip-knee-ankle angle (HKA), femoral component angle (FCA), and tibial
      component angle (TCA) on plain X-rays were evaluated for postoperative alignment.
      RESULTS: Corrections were made to the initial plans in 91.1% of cases with a mean
      of 3.3 corrections per knee. Intraoperative corrections were made in 57.8% of
      cases, with a mean of 0.6 corrections per knee. Mean absolute osteotomy error was
      around one millimeter, and values were within two millimeters over 80% of cases
      on most parts except the proximal lateral tibia. In terms of postoperative
      alignment, HKA was 178.5+/-1.7 degrees , FCA was 89.0+/-1.6 degrees , and TCA was
      89.4+/-1.9 degrees . Proportions of outliers were 11.1%, 15.6%, and 20.0%,
      respectively. CONCLUSIONS: Most of the cases required preoperative corrections
      for planning of PSI. PSI may be useful for ensuring the accuracy of osteotomy and
      postoperative alignment.

PMID- 29046243
TI  - A review of the TAEA proficiency test on natural and anthropogenic radionuclides
      activities in black tea.
AB  - A proficiency test amongst 15 Turkish laboratories with participation of 5 non
      Turkish laboratories was organized to determine the 137Cs, 40K and 90Sr massic
      activities in black tea powder samples. The bulk material, consisting of tea
      produced in 2014, was mixed with contaminated tea that was withdrawn from the
      market after the Chernobyl accident. Nineteen laboratories reported 41 results.
      The evaluation of the results was based on the accuracy and precision criteria
      adopted by the IAEA Proficiency Testing Group and resulted in 49% acceptable
      results, 19% acceptable with warning and 32% were found to be not acceptable.

PMID- 29046244
TI  - Endometrial resection and global ablation in the normal uterus.
AB  - There are various methods that can be used to destroy the endometrium as a
      treatment for menorrhagia. This chapter reviews the history, rationale, evidence,
      indications and long-term safety and efficacy of the current techniques. It also
      discusses endometrial ablation in the context of its clinical utility in
      comparison with existing alternative treatments.

PMID- 29046245
TI  - Point-of-care ultrasound in pyomyositis: A case series.

PMID- 29046246
TI  - Elevated body mass index is a risk factor associated with possible liver
      cirrhosis across different etiologies of chronic liver disease: Methodological
      issues.

PMID- 29046247
TI  - Optimal usage of radium-223 in metastatic castration-resistant prostate cancer.
AB  - Radium-223 is a first-in-class alpha-emitting radiopharmaceutical that targets
      bone metastases associated with metastatic castration-resistant prostate cancer
      (mCRPC). In the pivotal phase III trial ALSYMPCA, radium-223 significantly
      increased overall survival (OS), compared with placebo (median 14.9 vs 11.3
      months; hazard ratio 0.70; 95% CI 0.58-0.83; p < 0.001), in patients with mCRPC
      and symptomatic bone metastases-with a comparable safety profile. To optimize
      treatment outcomes, selection of appropriate patients is important. As well as
      osteoblastic bone metastases, mCRPC patients should be well enough to receive six
      doses of radium-223 as this treatment duration has been shown to greatly improve
      OS outcomes compared with administration of four or fewer doses. Additionally,
      alkaline phosphatase and lactate dehydrogenase are emerging as important
      biomarkers during radium-223 treatment. Optimal concomitant standard-of-care
      therapies (such as abiraterone or enzalutamide) to be administered with radium
      223 have yet to be defined as does the most efficacious dose and duration of
      radium-223 treatment. In conclusion, radium-223 is an important addition to the
      mCRPC treatment landscape and marks a paradigm shift in the treatment of bone
      metastases.

PMID- 29046248
TI  - Clinical characteristics and treatment outcomes of vancomycin-resistant
      Enterococcus faecium bacteremia.
AB  - BACKGROUND: Vancomycin-resistant Enterococcus faecium (VRE-fm) bacteremia causes
      significant mortality in hospitalized patients. We sought to investigate clinical
      characteristics, treatment outcomes, and microbiological eradication associated
      with VRE-fm bacteremia. METHODS: A retrospective cohort study was conducted and
      included 210 adult patients admitted between January 1, 2011 and December 31,
      2015. RESULTS: The mean Pitt bacteremia score was 4.7. ICU stay (48.6%) and
      mechanical ventilation (46.2%) were common. Diabetes mellitus was the most common
      concomitant disease (43.3%), followed by malignancies, including hematologic
      malignancies (14.3%) and solid cancers (28.1%). The 14-day and 28-day mortality
      rates were 37.1% and 50.5%, respectively. Linezolid or daptomycin treatment for
      at least 10 days and higher Pitt bacteremia scores were independently associated
      with 14-day and 28-day mortality. Longer treatment duration of linezolid or
      daptomycin predicted microbiological eradication independently. Daptomycin
      treated patients tended to have higher 14-day and 28-day mortality, and lower
      microbial eradication rates (20.8% versus 8.7%; 40.6% versus 26.1%; 14.1% versus
      26.1%; respectively) than linezolid-treated patients, and cumulative survival
      rates at 14 and 28 days tended to be lower in patients who received low-dose
      daptomycin (<10 mg/kg/day) than that in those who received linezolid and high
      dose daptomycin (>=10 mg/kg/day); however, the differences were not statistically
      significant. CONCLUSION: Higher disease severity and inappropriate treatment were
      associated with increased mortality and longer treatment duration of linezolid or
      daptomycin was associated with microbial eradication for the patient with VRE-fm
      bacteremia.

PMID- 29046249
TI  - Humoral immunity to mumps in a highly vaccinated population in Taiwan.
AB  - BACKGROUND: A resurgence of mumps was noted recently and outbreaks were
      increasingly reported in populations with high vaccine coverage. We aimed to
      evaluate the seroprevalence to mumps in Taiwan, where a two-dose childhood mumps
      containing vaccine program, with a high coverage rate, had been implemented for
      >20 years. METHODS: The anti-mumps IgG was determined in 3552 participants of all
      ages in Taiwan. The age-specific seropositivity rates were calculated and the
      sociodemographic variables associated with the seronegative sera were analyzed
      with a logistic regression method. RESULTS: The overall seroprevalence to mumps
      was 71%, with a higher rate in adults >=19 years old than in the pediatric
      population <19 years old (80.4% versus 62.0%, P < 0.0001). In participants aged 2
      20 years, who had been given at least one mumps-containing vaccine, the
      seropositivity fluctuated across different age subgroups and the lowest rate
      (36.8%) occurred in the 17-18 years age group. The multivariate analysis
      identified age within 17-18 years (adjusted odds ratio [aOR] 8.598, 95%
      confidence interval [CI] 2.990-24.722, P < 0.0001), within 19-20 years (aOR
      5.076, 95% CI 1.702-15.133, P = 0.0080), and being a resident of the suburban
      area of northern Taiwan (aOR 1.089, 95% CI 0.823-1.414, P = 0.0008) as
      independent factors associated with an increased risk of seronegative sera.
      CONCLUSION: The seropositivity to mumps was unexpectedly low in highly vaccinated
      generations, and with a significant geographical discrepancy in Taiwan, which may
      have been responsible for the sustained reports of mumps cases in Taiwan.

PMID- 29046250
TI  - Response to 'Classification of cerebral palsy and potential role of video
      recording'.

PMID- 29046251
TI  - Mycobacterium tuberculosis ESAT6 induces IFN-beta gene expression in Macrophages
      via TLRs-mediated signaling.
AB  - Mycobacterium tuberculosis is a highly virulent bacterium that causes
      tuberculosis. It infects about one third of the world's population. Type I
      interferons (IFNs) play a detrimental role in host defense against M.
      tuberculosis infection. Proteins secreted by M. tuberculosis through ESX-1
      secretion system contribute to type I IFNs production. However, the precise
      mechanism by which 6-kDa early secretory antigen target (ESAT6), one of ESX-1
      mediated secretory proteins, induces type I IFNs production in host cells is
      currently unclear. Therefore, the objective of the present study was to determine
      the underlying molecular mechanism regulating ESAT6-mediated gene expression of
      IFN-beta in macrophages. Recombinant ESAT6 produced from E. coli expression
      system induced IFN-beta gene expression in various types of macrophages such as
      mouse bone marrow-derived macrophages (BMDMs), peritoneal macrophages, and MH-S
      cells (murine alveolar macrophage cell line). Deficiency of TLR4 and TRIF
      absolutely abrogated ESAT6-induced IFN-beta gene expression. TLR2 and MyD88 were
      partially involved in IFN-beta gene expression in response to low dose of ESAT6.
      Another recombinant ESAT6 produced from baculovirus system also upregulated IFN
      beta gene expression via TLR4-dependent pathway. Polymyxin B (PMB) treatment
      impaired LPS-induced IFN-beta expression. However, IFN-beta expression induced by
      ESAT6 was not influenced by PMB. This suggests that ESAT6-mediated IFN-beta
      expression is not due to LPS contamination. Treatment with ESAT6 resulted in
      activation of TBK1 and IRF3 in macrophages. Such activation was abolished in TLR4
      and TRIF-deficient cells. Moreover, inhibition of IRF3 and TBK1 suppressed IFN
      beta gene expression in response to ESAT6. Our results suggest that ESAT6 might
      contribute to virulence of M. tuberculosis by regulating type I IFNs production
      through TLR4-TRIF signaling pathway.

PMID- 29046252
TI  - Response to Letter "High serum soluble CD40L levels previously to liver
      transplantation in patients with hepatocellular carcinoma are associated with
      mortality at one year: Methodological issues".

PMID- 29046253
TI  - Addiction and schizophrenia: A translational perspective.

PMID- 29046254
TI  - Letter to the editor regarding Robinson PM et al: "Randomized controlled trial of
      supervised physiotherapy versus a home exercise program after hydrodilatation for
      the management of primary frozen shoulder".

PMID- 29046255
TI  - Platform shoulder arthroplasty: a systematic review.
AB  - BACKGROUND: Platform shoulder arthroplasty systems may allow conversion to a
      reverse total shoulder arthroplasty (RTSA) without removing a well-fixed, well
      positioned humeral stem. We sought to evaluate the complications associated with
      humeral stem exchange versus retention in patients undergoing conversion shoulder
      arthroplasty with a platform shoulder arthroplasty system. METHODS: PubMed,
      MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and
      Embase were searched from database inception through October 9, 2016, for all
      articles comparing humeral stem retention versus exchange during conversion RTSA
      or that pertained to conversion RTSA with stem retention alone. All studies were
      screened in duplicate for eligibility. A methodologic quality assessment was
      completed for included studies. Pooled outcomes assessing complications,
      operative time, blood loss, and reoperations were determined. RESULTS: We
      included 7 studies (236 shoulders), including 1 level III and 6 level IV studies.
      Pooled analysis demonstrated significantly higher overall complications (odds
      ratio, 6.89; 95% confidence interval [CI], 2.48-19.13; P = .0002), fractures
      (odds ratio, 4.62; 95% CI, 1.14-18.67; P = .03), operative time (mean difference,
      62.09 minutes; 95% CI, 51.17-73.01 minutes; P < .00001), and blood loss (mean
      difference, 260.06 mL; 95% CI, 165.30-354.83 mL; P < .00001) with humeral stem
      exchange. Stem exchange was also associated with increased risk of reoperation (P
      = .0437). CONCLUSION: Conversion arthroplasty with retention of the humeral stem
      is associated with lower overall complications, blood loss, operative time, and
      reoperations in comparison with stem exchange.

PMID- 29046256
TI  - Capping effects on polymorphic Abeta16-21 amyloids depend on their size: A
      molecular dynamics simulation study.
AB  - Understanding Abeta amyloid oligomers associated with neuro-degenerative diseases
      is needed due to their toxic characteristics and mediation of amyloid fibril
      growth. Depending on various physiological circumstances such as ionic strength,
      metal ion, and point-residue mutation, oligomeric amyloids exhibit polymorphic
      behavior and structural stabilities, i.e. showing different conformation and
      stabilities. Specifically, experimental and computational researchers have found
      that the capping modulates the physical and chemical properties of amyloids by
      preserving electrostatic energy interactions, which is one of the dominant
      factors for amyloid stability. Still, there is no detailed knowledge for the
      polymorphic amyloids with reflecting the terminal capping effects. In the present
      study, we investigated the role of terminal capping (i.e. N-terminal acetylation
      and C-terminal amidation) on polymorphic Abeta16-21 amyloid oligomer and
      protofibrils via molecular dynamics (MD) simulations. We found that the capping
      effects have differently altered the conformation of polymorphic antiparallel
      homo and -hetero Abeta16-21 amyloid oligomer, but not Abeta16-21 amyloid
      protofibrils. However, regardless of polymorphic composition of the amyloids, the
      capping induces the thermodynamic instabilities of Abeta16-21 amyloid oligomers,
      but does not show any distinct affect on Abeta16-21 amyloid protofibrils.
      Specifically, among the molecular mechanic factors, electrostatic energy
      dominantly contributes the thermodynamic stability of the Abeta16-21 amyloids. We
      hope that our computation study about the role of the capping effects on the
      polymorphic amyloids will facilitate additional efforts to enhance degradation of
      amyloids and to design a selective drug in the future.

PMID- 29046257
TI  - Response to "GHB concentration in breast milk of narcoleptic women treated with
      sodium oxybate. How important it is to be careful when interpreting values."
      (Letter to the Editor by Busardo PB and Pichini S).

PMID- 29046258
TI  - Association between statin exposure and venous thromboembolism risk in cancer
      patients. Data from the EDITH case-control study.

PMID- 29046259
TI  - Assessing the impact of quality improvement measures on catheter related blood
      stream infections and catheter salvage: Experience from a national intestinal
      failure unit.
AB  - BACKGROUND & AIMS: Prevention of catheter related blood stream infections (CRBSI)
      and salvage of infected central venous catheters (CVC) are vital to maintaining
      long term venous access in patients needing home parenteral nutrition (HPN). It
      remains unclear as to whether patients are best trained for catheter care at home
      or in hospital or whether CRBSIs are lower if the patient self-cares for the CVC.
      Furthermore, there is minimal data on the longer term outcome following salvage
      of infected catheter and limited consensus on agreed protocols for catheter
      salvage. METHOD: We conducted a retrospective 5-year evaluation of CRBSI
      occurrence and CVC salvage outcomes in adult patients requiring HPN managed at a
      national UK Intestinal Failure Unit from 2012 to 2016. Prior to 2012, patients
      were primarily trained to administer PN in hospital; thereafter, patients
      underwent training at home. RESULTS: A total of 134 CRBSI were recorded in 92
      patients (62 patients with a single CRBSI and 30 patients with more than 1 CRBSI)
      in a cohort of 559 HPN patients, with a total of 1163 HPN years. The overall
      CRBSI rate was 0.31 per 1000 catheter days. CNS were the most common isolates
      (41/134 (30.5%)), followed by polymicrobial infections (14/134 (10.4%)),
      Klebsiella spp. (16/134 (11.9%)) and methicillin - sensitive Staphylococcus
      aureus (MSSA) 5/134 ((3.7%)). Salvage was not attempted in 34 cases due to
      methicillin - resistant (MRSA) infection (1/34), fungal infection (13/34) or
      clinical instability due to sepsis (20/34). Of the 100 cases where salvage was
      attempted, 67% were successful. 82.8% of CNS salvage attempts were successful;
      there was no difference in salvage rates between CNS CRBSIs salvaged with a 10
      day (22/26) or 14-day protocol (7/9) (p = 0.4). CRBSI rate, in those cared for by
      trained home care nurses was the lowest at 0.270 (self care: 0.342 and non
      medical carer (e.g. family member): 0.320) (p = 0.03). CONCLUSION: We previously
      reported a sustained very low CRBSI rate in a large cohort of HPN patients in a
      national unit; we now further report that this is not influenced by training
      patients at home rather than in hospital but is influenced by the individual
      managing the catheter at home. CNS remains the primary cause of CRBSIs and can be
      successfully salvaged with a reduced duration of antibiotic therapy compared to
      our previous experience.

PMID- 29046260
TI  - Assessment of liver regeneration after associating liver partition and portal
      vein ligation for staged hepatectomy: a comparative study with portal vein
      ligation.
AB  - BACKGROUND: To investigate the diagnostic value of diffusion kurtosis imaging
      (DKI) and diffusion-weighted imaging (DWI) in assessing liver regeneration after
      associating liver partition and portal vein ligation for staged hepatectomy
      (ALPPS) compared with portal vein ligation (PVL). METHODS: Thirty rats were
      divided into the ALPPS, PVL, and control groups. DKI and DWI were performed
      before and 7 days after surgery. Corrected apparent diffusion (D), kurtosis (K)
      and apparent diffusion coefficient (ADC) were calculated and compared, radiologic
      pathologic correlations were evaluated. RESULTS: The volume of the right median
      lobe increased significantly after ALPPS. There were larger cellular diameters
      after ALPPS and PVL (P = 0.0003). The proliferative indexes of Ki-67 and
      hepatocyte growth factor were higher after ALPPS (P = 0.0024/0.0433). D, K and
      ADC values differed between the groups (P = 0.021/0.0015/0.0008). A significant
      correlation existed between D and the hepatocyte size (r = -0.523), no
      correlations existed in ADC and K (P = 0.159/0.111). The proliferative indexes
      showed moderate negative correlations with ADC (r = -0.484/-0.537) and no
      correlations with D and K (P = 0.100-0.877). DISCUSSION: Liver regeneration after
      ALPPS was effective and superior to PVL. DKI, especially the D map, may provide
      added value in evaluating the microstructure of liver regeneration after ALPPS,
      but this model alone may perform no better than the standard monoexponential
      model of DWI.

PMID- 29046262
TI  - Effect of MRI on breast tissue expanders and recommendations for safe use.
AB  - INTRODUCTION: Ferromagnetic port-containing breast tissue expanders are currently
      labeled MRI-unsafe because of the presumption that magnets should not enter the
      machine. However, designating these devices as MRI-unsafe can lead to unnecessary
      procedures or suboptimal imaging choices. This study provides an ex vivo analysis
      of how breast tissue expanders behave when subjected to strong magnetic fields to
      determine which variables might affect clinical risk. METHODS: Three different
      brands of tissue expanders were evaluated in three MRI environments.
      Translational force was determined using the deflection angle method. Torque on
      empty, saline-filled, and air-filled expanders was evaluated on a 0-4 scale.
      Magnetic field was measured using a gaussmeter. The weight required to prevent
      displacement of the expanders was determined for both air- and saline-filled
      expanders. Temperature over time was measured using an alcohol thermometer.
      RESULTS: Magnetic field strength, deflection angle, and torque were the greatest
      in 3T MRI environments and varied by device manufacturer (Sientra > Mentor >
      Allergan). Saline-filled expanders required 240 mL and air-filled required 360 mL
      volume to make the torque undetectable, and the effect of torque could be
      mitigated with prone positioning. A weight of 120 g was required to prevent
      displacement of a saline-filled tissue expander and 870 g for an empty expander.
      There were no appreciable changes in temperature. CONCLUSIONS: Previously
      described risks may be reduced by using a 1.5T MRI, device selection, filling
      expanders with saline, and prone positioning. MRI can be considered in patients
      with breast tissue expanders when appropriate peri-procedural choices have been
      made so that the benefits of undergoing MRI outweigh the risks.

PMID- 29046261
TI  - Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic
      reprogramming.
AB  - OBJECTIVE: Cinnamaldehyde (CA) is a food compound that has previously been
      observed to be protective against obesity and hyperglycemia in mouse models. In
      this study, we aimed to elucidate the mechanisms behind this protective effect by
      assessing the cell-autonomous response of primary adipocytes to CA treatment.
      METHODS: Primary murine adipocytes were treated with CA and thermogenic and
      metabolic responses were assessed after both acute and chronic treatments. Human
      adipose stem cells were differentiated and treated with CA to assess whether the
      CA-mediated signaling is conserved in humans. RESULTS: CA significantly activated
      PKA signaling, increased expression levels of thermogenic genes and induced
      phosphorylation of HSL and PLIN1 in murine primary adipocytes. Inhibition of PKA
      or p38 MAPK enzymatic activity markedly inhibited the CA-induced thermogenic
      response. In addition, chronic CA treatment regulates metabolic reprogramming,
      which was partially diminished in FGF21KO adipocytes. Importantly, both acute and
      chronic effects of CA were observed in human adipose stem cells isolated from
      multiple donors of different ethnicities and ages and with a variety of body mass
      indexes (BMI). CONCLUSIONS: CA activates thermogenic and metabolic responses in
      mouse and human primary subcutaneous adipocytes in a cell-autonomous manner,
      giving a mechanistic explanation for the anti-obesity effects of CA observed
      previously and further supporting its potential metabolic benefits on humans.
      Given the wide usage of cinnamon in the food industry, the notion that this
      popular food additive, instead of a drug, may activate thermogenesis, could
      ultimately lead to therapeutic strategies against obesity that are much better
      adhered to by participants.

PMID- 29046263
TI  - Improvement of extracellular bacterial protein production in Pichia pastoris by
      co-expression of endoplasmic reticulum residing GroEL-GroES.
AB  - Pichia pastoris is an established host system for heterologous protein
      expression. However, the potential productivity of this system can be limited. In
      this study, the Escherichia coli chaperones (GroES-GroEL) were expressed from the
      PGAP promoter and targeted to the secretory pathway through the endoplasmic
      reticulum (ER). The ability of the ER targeted chaperones to improve production
      of bacterial protein in P. pastoris was evaluated. The chaperones tagged with
      alpha-factor secretion- and ER retention-signal sequences were co-expressed with
      either extracellularly secreted phytase or intracellular d-phenylglycine
      aminotransferase (D-PhgAT) enzymes. The ER residing GroEL-GroES successfully
      increased the levels of active phytase extracellularly, 1.5-2.3-fold higher than
      the phytase expression alone, but did not enhance the formation of active,
      intracellular D-PhgAT. These results indicate that the chaperones have the
      potential to enhance production of active enzymes when present in the same
      trafficking pathway. This is the first report on the improvement of extracellular
      bacterial protein production through co-expression with ER residing bacterial
      chaperones in the Pichia system. The modified P. pastoris expression system may
      be beneficial for extracellular expression of other prokaryotic proteins.

PMID- 29046264
TI  - Carbohydrate-binding module assisted purification and immobilization of beta
      glucosidase onto cellulose and application in hydrolysis of soybean isoflavone
      glycosides.
AB  - Complicated purification steps, together with the fact that beta-glucosidase has
      to be tolerant to ethanol restricts the application of beta-glucosidase in
      isoflavone aglycone hydrolyzing process. beta-Glucosidase Bgl1A(A24S/F297Y) is a
      promising enzyme in hydrolyzing isoflavones. In this work, six different
      carbohydrate-binding modules (CBMs), which were from 3 families, were fused to
      the C-terminal of Bgl1A(A24S/F297Y), respectively, to simplify the enzyme
      preparation process. The fusion proteins were expressed in Escherichia coli and
      adsorbed onto cellulose. The Bgl-CBM24 was found to have the highest
      immobilization efficiency at room temperature within 1 h adsorption. Notably, 1-g
      cellulose absorbs up to 254.9+/-5.7 U of Bgl-CBM24. Interestingly, the
      immobilized Bgl-CBM24 showed improved ethanol tolerance ability, with the IC50 of
      35% (v/v) ethanol. Bgl-CBM24 effectively hydrolyze soybean isoflavone glycosides.
      The hydrolysis rate of daidzin and gemistin was 85.22+/-3.24% and 82.14+/-3.82%
      within 10 min, with the concentrations of daidzein and genistein increased by
      6.36+/-0.18 mM and 3.98+/-0.22 mM, respectively. In the repetitive hydrolytic
      cycles, the concentrations of daidzein and genistein still increased by 3.07+/
      0.24 mM and 1.94+/-0.34 mM in the fourth cycle with 20% (v/v) ethanol. These
      results suggest that the immobilized Bgl-CBM24 has excellent potential in the
      preparation of isoflavone aglycones.

PMID- 29046266
TI  - Guidelines and mHealth to Improve Quality of Hypertension and Type 2 Diabetes
      Care for Vulnerable Populations in Lebanon: Longitudinal Cohort Study.
AB  - BACKGROUND: Given the protracted nature of the crisis in Syria, the large
      noncommunicable disease (NCD) caseload of Syrian refugees and host Lebanese, and
      the high costs of providing NCD care, the implications for Lebanon's health
      system are vast. OBJECTIVE: The aim of this study was to evaluate the
      effectiveness of treatment guidelines and a mobile health (mHealth) app on
      quality of care and health outcomes in primary care settings in Lebanon. METHODS:
      A longitudinal cohort study was implemented from January 2015 to August 2016 to
      evaluate the effectiveness of treatment guidelines and an mHealth app on quality
      of care and health outcomes for Syrian and Lebanese patients in Lebanese primary
      health care (PHC) facilities. RESULTS: Compared with baseline record extraction,
      recording of blood pressure (BP) readings (-11.4%, P<.001) and blood sugar
      measurements (-6.9%, P=.03) significantly decreased following the implementation
      of treatment guidelines. Recording of BP readings also decreased after the
      mHealth phase as compared with baseline (-8.4%, P=.001); however, recording of
      body mass index (BMI) reporting increased at the end of the mHealth phase from
      baseline (8.1%, P<.001) and the guidelines phase (7.7%, P<.001). There were a
      great proportion of patients for whom blood sugar, BP, weight, height, and BMI
      were recorded using the tablet compared with in paper records; however, only
      differences in BMI were statistically significant (31.6% higher in app data as
      compared with paper records; P<.001). Data extracted from the mHealth app showed
      that a higher proportion of providers offered lifestyle counseling compared with
      the counseling reported in patients' paper records (health diet counseling; 77.3%
      in app data vs 8.8% in paper records, P<.001 and physical activity counseling and
      59.7% in app vs 7.1% in paper records, P<.001). There were statistically
      significant increases in all four measures of patient-provider interaction across
      study phases. Provider inquiry of medical history increased by 16.6% from
      baseline following guideline implementation and by 28.2% from baseline to mHealth
      implementation (P<.001). From baseline, patient report of provider inquiry
      regarding medication complications increased in the guidelines and mHealth phases
      by 12.9% and 59.6%, respectively, (P<.001). The proportion of patients reporting
      that providers asked other questions relevant to their illness increased from
      baseline through guidelines implementation by 27.8% and to mHealth implementation
      by 66.3% (P<.001). Follow-up scheduling increased from baseline to the guidelines
      phase by 20.6% and the mHealth phase by 39.8% (P<.001). CONCLUSIONS: Results from
      this study of an mHealth app in 10 PHC facilities in Lebanon indicate that the
      app has potential to improve adherence to guidelines and quality of care. Further
      studies are necessary to determine the effects of patient-controlled health
      record apps on provider adherence to treatment guidelines, as well as patients'
      long-term medication and treatment adherence and disease control.

PMID- 29046265
TI  - Using the Internet to Train Therapists: Randomized Comparison of Two Scalable
      Methods.
AB  - BACKGROUND: One of the major barriers to the dissemination and implementation of
      psychological treatments is the scarcity of suitably trained therapists. The
      currently accepted method of training is not scalable. Recently, a scalable form
      of training, Web-centered training, has been shown to have promise. OBJECTIVE:
      The goal of our research was to conduct a randomized comparison of the relative
      effects of independent and supported Web-centered training on therapist
      competence and investigate the persistence of the effects. METHODS: Eligible
      therapists were recruited from across the United States and Canada. They were
      randomly assigned to 1 of 2 forms of training in enhanced cognitive behavior
      therapy (CBT-E), a multicomponent evidence-based psychological treatment for any
      form of eating disorder. Independent training was undertaken autonomously, while
      supported training was accompanied by support from a nonspecialist worker.
      Therapist competence was assessed using a validated competence measure before
      training, after 20 weeks of training, and 6 months after the completion of
      training. RESULTS: A total of 160 therapists expressed interest in the study, and
      156 (97.5%) were randomized to the 2 forms of training (81 to supported training
      and 75 to independent training). Mixed effects analysis showed an increase in
      competence scores in both groups. There was no difference between the 2 forms of
      training, with mean difference for the supported versus independent group being 
      0.06 (95% Cl -1.29 to 1.16, P=.92). A total of 58 participants (58/114, 50.9%)
      scored above the competence threshold; three-quarters (43/58, 74%) had not met
      this threshold before training. There was no difference between the 2 groups in
      the odds of scoring over the competence threshold (odds ratio [OR] 1.02, 95% CI
      0.52 to 1.99; P=.96). At follow-up, there was no significant difference between
      the 2 training groups (mean difference 0.19, 95% Cl -1.27 to 1.66, P=.80).
      Overall, change in competence score from end of training to follow-up was not
      significant (mean difference -0.70, 95% CI -1.52 to 0.11, P=.09). There was also
      no difference at follow-up between the training groups in the odds of scoring
      over the competence threshold (OR 0.95, 95% Cl 0.34 to 2.62; P=.92). CONCLUSIONS:
      Web-centered training was equally effective whether undertaken independently or
      accompanied by support, and its effects were sustained. The independent form of
      Web-centered training is particularly attractive as it provides a means of
      training large numbers of geographically dispersed therapists at low cost,
      thereby overcoming several obstacles to the widespread dissemination of
      psychological treatments.

PMID- 29046267
TI  - Identifying Sentiment of Hookah-Related Posts on Twitter.
AB  - BACKGROUND: The increasing popularity of hookah (or waterpipe) use in the United
      States and elsewhere has consequences for public health because it has similar
      health risks to that of combustible cigarettes. While hookah use rapidly
      increases in popularity, social media data (Twitter, Instagram) can be used to
      capture and describe the social and environmental contexts in which individuals
      use, perceive, discuss, and are marketed this tobacco product. These data may
      allow people to organically report on their sentiment toward tobacco products
      like hookah unprimed by a researcher, without instrument bias, and at low costs.
      OBJECTIVE: This study describes the sentiment of hookah-related posts on Twitter
      and describes the importance of debiasing Twitter data when attempting to
      understand attitudes. METHODS: Hookah-related posts on Twitter (N=986,320) were
      collected from March 24, 2015, to December 2, 2016. Machine learning models were
      used to describe sentiment on 20 different emotions and to debias the data so
      that Twitter posts reflected sentiment of legitimate human users and not of
      social bots or marketing-oriented accounts that would possibly provide overly
      positive or overly negative sentiment of hookah. RESULTS: From the analytical
      sample, 352,116 tweets (59.50%) were classified as positive while 177,537
      (30.00%) were classified as negative, and 62,139 (10.50%) neutral. Among all
      positive tweets, 218,312 (62.00%) were classified as highly positive emotions
      (eg, active, alert, excited, elated, happy, and pleasant), while 133,804 (38.00%)
      positive tweets were classified as passive positive emotions (eg, contented,
      serene, calm, relaxed, and subdued). Among all negative tweets, 95,870 (54.00%)
      were classified as subdued negative emotions (eg, sad, unhappy, depressed, and
      bored) while the remaining 81,667 (46.00%) negative tweets were classified as
      highly negative emotions (eg, tense, nervous, stressed, upset, and unpleasant).
      Sentiment changed drastically when comparing a corpus of tweets with social bots
      to one without. For example, the probability of any one tweet reflecting joy was
      61.30% from the debiased (or bot free) corpus of tweets. In contrast, the
      probability of any one tweet reflecting joy was 16.40% from the biased corpus.
      CONCLUSIONS: Social media data provide researchers the ability to understand
      public sentiment and attitudes by listening to what people are saying in their
      own words. Tobacco control programmers in charge of risk communication may
      consider targeting individuals posting positive messages about hookah on Twitter
      or designing messages that amplify the negative sentiments. Posts on Twitter
      communicating positive sentiment toward hookah could add to the normalization of
      hookah use and is an area of future research. Findings from this study
      demonstrated the importance of debiasing data when attempting to understand
      attitudes from Twitter data.

PMID- 29046268
TI  - Multisite Semiautomated Clinical Data Repository for Duplication 15q Syndrome:
      Study Protocol and Early Uses.
AB  - BACKGROUND: Chromosome 15q11.2-q13.1 duplication syndrome (Dup15q syndrome) is a
      rare disorder caused by duplications of chromosome 15q11.2-q13.1, resulting in a
      wide range of developmental disabilities in affected individuals. The Dup15q
      Alliance is an organization that provides family support and promotes research to
      improve the quality of life of patients living with Dup15q syndrome. Because of
      the low prevalence of this condition, the establishment of a single research
      repository would have been difficult and more time consuming without
      collaboration across multiple institutions. OBJECTIVE: The goal of this project
      is to establish a national deidentified database with clinical and survey
      information on individuals diagnosed with Dup15q syndrome. METHODS: The
      development of a multiclinic site repository for clinical and survey data on
      individuals with Dup15q syndrome was initiated and supported by the Dup15q
      Alliance. Using collaborative workflows, communication protocols, and stakeholder
      engagement tools, a comprehensive database of patient-centered information was
      built. RESULTS: We successfully established a self-report populating, centralized
      repository for Dup15q syndrome research. This repository also resulted in the
      development of standardized instruments that can be used for other studies
      relating to developmental disorders. By standardizing the data collection
      instruments, it allows us integrate our data with other national databases, such
      as the National Database for Autism Research. A substantial portion of the data
      collected from the questionnaires was facilitated through direct engagement of
      participants and their families. This allowed for a more complete set of
      information to be collected with a minimal turnaround time. CONCLUSIONS: We
      developed a repository that can efficiently be mined for shared clinical
      phenotypes observed at multiple clinic sites and used as a springboard for future
      clinical and basic research studies.

PMID- 29046269
TI  - What Clinical Information Is Valuable to Doctors Using Mobile Electronic Medical
      Records and When?
AB  - BACKGROUND: There has been a lack of understanding on what types of specific
      clinical information are most valuable for doctors to access through mobile-based
      electronic medical records (m-EMRs) and when they access such information.
      Furthermore, it has not been clearly discussed why the value of such information
      is high. OBJECTIVE: The goal of this study was to investigate the types of
      clinical information that are most valuable to doctors to access through an m-EMR
      and when such information is accessed. METHODS: Since 2010, an m-EMR has been
      used in a tertiary hospital in Seoul, South Korea. The usage logs of the m-EMR by
      doctors were gathered from March to December 2015. Descriptive analyses were
      conducted to explore the overall usage patterns of the m-EMR. To assess the value
      of the clinical information provided, the usage patterns of both the m-EMR and a
      hospital information system (HIS) were compared on an hourly basis. The peak
      usage times of the m-EMR were defined as continuous intervals having normalized
      usage values that are greater than 0.5. The usage logs were processed as an
      indicator representing specific clinical information using factor analysis.
      Random intercept logistic regression was used to explore the type of clinical
      information that is frequently accessed during the peak usage times. RESULTS: A
      total of 524,929 usage logs from 653 doctors (229 professors, 161 fellows, and
      263 residents; mean age: 37.55 years; males: 415 [63.6%]) were analyzed. The
      highest average number of m-EMR usage logs (897) was by medical residents,
      whereas the lowest (292) was by surgical residents. The usage amount for three
      menus, namely inpatient list (47,096), lab results (38,508), and investigation
      list (25,336), accounted for 60.1% of the peak time usage. The HIS was used most
      frequently during regular hours (9:00 AM to 5:00 PM). The peak usage time of the
      m-EMR was early in the morning (6:00 AM to 10:00 AM), and the use of the m-EMR
      from early evening (5:00 PM) to midnight was higher than during regular business
      hours. Four factors representing the types of clinical information were extracted
      through factor analysis. Factors related to patient investigation status and
      patient conditions were associated with the peak usage times of the m-EMR
      (P<.01). CONCLUSIONS: Access to information regarding patient investigation
      status and patient conditions is crucial for decision making during morning
      activities, including ward rounds. The m-EMRs allow doctors to maintain the
      continuity of their clinical information regardless of the time and location
      constraints. Thus, m-EMRs will best evolve in a manner that enhances the
      accessibility of clinical information helpful to the decision-making process
      under such constraints.

PMID- 29046270
TI  - #MyDepressionLooksLike: Examining Public Discourse About Depression on Twitter.
AB  - BACKGROUND: Social media provides a context for billions of users to connect,
      express sentiments, and provide in-the-moment status updates. Because Twitter
      users tend to tweet emotional updates from daily life, the platform provides
      unique insights into experiences of mental health problems. Depression is not
      only one of the most prevalent health conditions but also carries a social
      stigma. Yet, opening up about one's depression and seeking social support may
      provide relief from symptoms. OBJECTIVE: The aim of this study was to examine the
      public discourse of the trending hashtag #MyDepressionLooksLike to look more
      closely at how users talk about their depressive symptoms on Twitter. METHODS: We
      captured 3225 original content tweets for the hashtag #MyDepressionLooksLike that
      circulated in May of 2016. Eliminating public service announcements, spam, and
      tweets with links to pictures or videos resulted in a total of 1978 tweets. Using
      qualitative content analysis, we coded the tweets to detect themes. RESULTS: The
      content analysis revealed seven themes: dysfunctional thoughts, lifestyle
      challenges, social struggles, hiding behind a mask, apathy and sadness, suicidal
      thoughts and behaviors, and seeking relief. CONCLUSIONS: The themes revealed
      important information about the content of the public messages that people share
      about depression on Twitter. More research is needed to understand the effects of
      the hashtag on increasing social support for users and reducing social stigma
      related to depression.

PMID- 29046271
TI  - Client-Focused Security Assessment of mHealth Apps and Recommended Practices to
      Prevent or Mitigate Transport Security Issues.
AB  - BACKGROUND: Mobile health (mHealth) apps show a growing importance for patients
      and health care professionals. Apps in this category are diverse. Some display
      important information (ie, drug interactions), whereas others help patients to
      keep track of their health. However, insufficient transport security can lead to
      confidentiality issues for patients and medical professionals, as well as safety
      issues regarding data integrity. mHealth apps should therefore deploy intensified
      vigilance to protect their data and integrity. This paper analyzes the state of
      security in mHealth apps. OBJECTIVE: The objectives of this study were as
      follows: (1) identification of relevant transport issues in mHealth apps, (2)
      development of a platform for test purposes, and (3) recommendation of practices
      to mitigate them. METHODS: Security characteristics relevant to the transport
      security of mHealth apps were assessed, presented, and discussed. These
      characteristics were used in the development of a prototypical platform
      facilitating streamlined tests of apps. For the tests, six lists of the 10 most
      downloaded free apps from three countries and two stores were selected. As some
      apps were part of these top 10 lists in more than one country, 53 unique apps
      were tested. RESULTS: Out of the 53 apps tested from three European App Stores
      for Android and iOS, 21/53 (40%) showed critical results. All 21 apps failed to
      guarantee the integrity of data displayed. A total of 18 apps leaked private data
      or were observable in a way that compromised confidentiality between apps and
      their servers; 17 apps used unprotected connections; and two apps failed to
      validate certificates correctly. None of the apps tested utilized certificate
      pinning. Many apps employed analytics or ad providers, undermining user privacy.
      CONCLUSIONS: The tests show that many mHealth apps do not apply sufficient
      transport security measures. The most common security issue was the use of any
      kind of unprotected connection. Some apps used secure connections only for
      selected tasks, leaving all other traffic vulnerable.

PMID- 29046272
TI  - Department of Health issues warning over cut price GP indemnity cover.

PMID- 29046273
TI  - Upright versus lying down position in second stage of labour in nulliparous women
      with low dose epidural: BUMPES randomised controlled trial.
AB  - Objective To determine whether being upright in the second stage of labour in
      nulliparous women with a low dose epidural increases the chance of spontaneous
      vaginal birth compared with lying down.Design Multicentre pragmatic individually
      randomised controlled trial.Setting 41 UK hospital labour wards.Participants 3093
      nulliparous women aged 16 or older, at term with a singleton cephalic
      presentation and in the second stage of labour with epidural
      analgesia.Interventions Women were allocated to an upright or lying down
      position, using a secure web based randomisation service, stratified by centre,
      with no masking of participants or clinicians to the trial interventions.Main
      outcome measures The primary outcome was spontaneous vaginal birth. Women were
      analysed in the groups into which they were randomly allocated, regardless of
      position recorded at any time during the second stage of labour (excluding women
      with no valid consent, who withdrew, or who did not reach second stage before
      delivery). Secondary outcomes included mode of birth, perineal trauma, infant
      Apgar score <4 at five minutes, admission to a neonatal unit, and longer term
      included maternal physical and psychological health, incontinence, and infant
      gross developmental delay. Results Between 4 October 2010 and 31 January 2014,
      3236 women were randomised and 3093 (95.6%) included in the primary analysis
      (1556 in the upright group and 1537 in the lying down group). Significantly fewer
      spontaneous vaginal births occurred in women in the upright group: 35.2%
      (548/1556) compared with 41.1% (632/1537) in the lying down group (adjusted risk
      ratio 0.86, 95% confidence interval 0.78 to 0.94). This represents a 5.9%
      absolute increase in the chance of spontaneous vaginal birth in the lying down
      group (number needed to treat 17, 95% confidence interval 11 to 40). No evidence
      of differences was found for most of the secondary maternal, neonatal, or longer
      term outcomes including instrumental vaginal delivery (adjusted risk ratio 1.08,
      99% confidence interval 0.99 to 1.18), obstetric anal sphincter injury (1.27,
      0.88 to 1.84), infant Apgar score <4 at five minutes (0.66, 0.06 to 6.88), and
      maternal faecal incontinence at one year (1.18, 0.61 to 2.28).Conclusions
      Evidence shows that lying down in the second stage of labour results in more
      spontaneous vaginal births in nulliparous women with epidural analgesia, with no
      apparent disadvantages in relation to short or longer term outcomes for mother or
      baby.Trial registration Current Controlled Trials ISRCTN35706297.

PMID- 29046274
TI  - Genetic Depletion or Hyperresponsiveness of Natural Killer Cells Do Not Affect
      Atherosclerosis Development.
AB  - RATIONALE: Chronic inflammation is central in the development of atherosclerosis.
      Both innate and adaptive immunities are involved. Although several studies have
      evaluated the functions of natural killer (NK) cells in experimental animal
      models of atherosclerosis, it is not yet clear whether NK cells behave as
      protective or proatherogenic effectors. One of the main caveats of previous
      studies was the lack of specificity in targeting loss or gain of function of NK
      cells. OBJECTIVES: We used 2 selective genetic approaches to investigate the role
      of NK cells in atherosclerosis: (1) Ncr1iCre/+R26lsl-DTA/+ mice in which NK cells
      were depleted and (2) Noe mice in which NK cells are hyperresponsive. METHODS AND
      RESULTS: No difference in atherosclerotic lesion size was found in Ldlr-/- (low
      density lipoprotein receptor null) mice transplanted with bone marrow (BM) cells
      from Ncr1iCreR26Rlsl-DTA , Noe, or wild-type mice. Also, no difference was
      observed in plaque composition in terms of collagen content, macrophage
      infiltration, or the immune profile, although Noe chimera had more IFN
      (interferon)-gamma-producing NK cells, compared with wild-type mice. Then, we
      investigated the NK-cell selectivity of anti-asialoganglioside M1 antiserum,
      which was previously used to conclude the proatherogenicity of NK cells. Anti
      asialoganglioside M1 treatment decreased atherosclerosis in both Ldlr-/- mice
      transplanted with Ncr1iCreR26Rlsl-DTA or wild-type bone marrow, indicating that
      its antiatherogenic effects are unrelated to NK-cell depletion, but to CD8+ T and
      NKT cells. Finally, to determine whether NK cells could contribute to the disease
      in conditions of pathological NK-cell overactivation, we treated irradiated Ldlr
      /- mice reconstituted with either wild-type or Ncr1iCreR26Rlsl-DTA bone marrow
      with the viral mimic polyinosinic:polycytidylic acid and found a significant
      reduction of plaque size in NK-cell-deficient chimeric mice. CONCLUSIONS: Our
      findings, using state-of-the-art mouse models, demonstrate that NK cells have no
      direct effect on the natural development of hypercholesterolemia-induced
      atherosclerosis, but may play a role when an additional systemic NK-cell
      overactivation occurs.

PMID- 29046276
TI  - Anaesthetist is jailed after stealing codeine from hospital where he no longer
      worked.

PMID- 29046275
TI  - Authors of US dermatology guidelines did not declare conflicts of interest.

PMID- 29046277
TI  - Upfront charging of overseas visitors using the NHS.

PMID- 29046279
TI  - Five minute with . . . Jeannie Watkins.

PMID- 29046280
TI  - Communication and a public campaign needed for expectations in frailty to become
      realistic.

PMID- 29046278
TI  - Incidence, clinical management, and mortality risk following self harm among
      children and adolescents: cohort study in primary care.
AB  - Objectives To examine temporal trends in sex and age specific incidence of self
      harm in children and adolescents, clinical management patterns, and risk of cause
      specific mortality following an index self harm episode at a young age.Design
      Population based cohort study.Setting UK Clinical Practice Research Datalink
      electronic health records from 647 general practices, with practice level
      deprivation measured ecologically using the index of multiple deprivation.
      Patients from eligible English practices were linked to hospital episode
      statistics (HES) and Office for National Statistics (ONS) mortality
      records.Participants For the descriptive analytical phases we examined data
      pertaining to 16 912 patients aged 10-19 who harmed themselves during 2001-14.
      For analysis of cause specific mortality following self harm, 8638 patients
      eligible for HES and ONS linkage were matched by age, sex, and general practice
      with up to 20 unaffected children and adolescents (n=170 274).Main outcome
      measures In the first phase, temporal trends in sex and age specific annual
      incidence were examined. In the second phase, clinical management was assessed
      according to the likelihood of referral to mental health services and
      psychotropic drug prescribing. In the third phase, relative risks of all cause
      mortality, unnatural death (including suicide and accidental death), and fatal
      acute alcohol or drug poisoning were estimated as hazard ratios derived from
      stratified Cox proportional hazards models for the self harm cohort versus the
      matched unaffected comparison cohort.Results The annual incidence of self harm
      was observed to increase in girls (37.4 per 10 000) compared with boys (12.3 per
      10 000), and a sharp 68% increase occurred among girls aged 13-16, from 45.9 per
      10 000 in 2011 to 77.0 per 10 000 in 2014. Referrals within 12 months of the
      index self harm episode were 23% less likely for young patients registered at the
      most socially deprived practices, even though incidences were considerably higher
      in these localities. Children and adolescents who harmed themselves were
      approximately nine times more likely to die unnaturally during follow-up, with
      especially noticeable increases in risks of suicide (deprivation adjusted hazard
      ratio 17.5, 95% confidence interval 7.6 to 40.5) and fatal acute alcohol or drug
      poisoning (34.3, 10.2 to 115.7).Conclusions Gaining a better understanding of the
      mechanisms responsible for the recent apparent increase in the incidence of self
      harm among early-mid teenage girls, and coordinated initiatives to tackle health
      inequalities in the provision of services to distressed children and adolescents,
      represent urgent priorities for multiple public agencies.

PMID- 29046281
TI  - Free fatty acid flux measured using [1-11C]palmitate positron emission tomography
      and [U-13C]palmitate in humans.
AB  - PET radiopharmaceuticals can noninvasively measure free fatty acid (FFA) tissue
      uptake. Investigators often use PET scan-derived data to calculate FFA flux. We
      tested whether the [1-11C]palmitate PET measures of palmitate flux provide
      results equivalent to a continuous infusion of [U-13C]palmitate. Nine volunteers
      participated in study 1 to evaluate whether a rapidly (10-20 s) given bolus of [1
      11C]palmitate affects calculated flux results. Thirty volunteers participated in
      study 2, which was identical to study 1 except that the [1-11C]palmitate bolus
      was given over 1 min. Volunteers in both studies also received a continuous
      intravenous infusion of [U-13C]palmitate. Plasma palmitate concentrations and
      enrichment were measured by liquid chromatography-mass spectrometry. The PET/CT
      images were analyzed on a workstation running PMOD. Palmitate flux was estimated
      using PET time-activity curve (TAC) data from regions of interest in the left
      ventricle (LV) and aorta both with and without hybrid TACs that employed the
      11CO2-corrected data for the first 5 min and the 11CO2-corrected blood
      radioactivity for the remainder of the PET scan. Palmitate flux in study 1
      measured with PET [1-11C]palmitate and [U-13C]palmitate were not correlated, and
      the PET [1-11C]palmitate flux was significantly less than the [U-13C]palmitate
      measured flux. In study 2, the palmitate flux using PET [1-11C]palmitate hybrid
      LV models provided closer mean estimates of [U-13C]palmitate measured flux. The
      best PET calculation approaches predicted 64% of the interindividual variance in
      [U-13C]palmitate measured flux. Palmitate kinetics measured using [1
      11C]palmitate/PET do not provide the same palmitate kinetic results as the
      continuous infusion [U-13C]palmitate approach.

PMID- 29046283
TI  - Pfizer and Cipla plan to make cancer drugs affordable in Africa.

PMID- 29046284
TI  - Blood lines.

PMID- 29046282
TI  - Clonality in context: hematopoietic clones in their marrow environment.
AB  - Clonal hematopoiesis occurs normally, especially with aging, and in the setting
      of disease, not only in myeloid cancers but in bone marrow failure as well. In
      cancer, malignant clones are characterized by recurrent somatic mutations in
      specific sets of genes, but the direct relationship of such mutations to
      leukemogenesis, when they occur in cells of an apparently healthy older
      individual or after recovery from immune aplastic anemia, is uncertain. Here we
      emphasize a view of clonal evolution that stresses natural selection over
      deterministic ontogeny, and we stress the selective role of the environment of
      the marrow and organism. Clonal hematopoieses after chemotherapy, in marrow
      failure, and with aging serve as models. We caution against the
      overinterpretation of clinical results of genomic testing in the absence of a
      better understanding of clonal selection and evolution.

PMID- 29046287
TI  - Nazneen Rahman: In tune with genetics.

PMID- 29046286
TI  - Primary care management of postoperative shoulder, hip, and knee arthroplasty.

PMID- 29046288
TI  - Formative care is needed for "progressive dwindling".

PMID- 29046289
TI  - A novel model to predict positive prostate biopsy based on serum androgen level.
AB  - Circulating levels of prostate-specific antigen (PSA) and testosterone are widely
      used for the detection of prostate cancer prior to prostate biopsy; however, both
      remain controversial. Effective screening strategies based on quantitative
      factors could help avoid unnecessary biopsies. Here, we sought to clarify the
      predictive value of free testosterone (FT) vs total testosterone (TT) in
      identifying patients likely to have positive biopsies. This study aims to develop
      a novel model for predicting positive prostate biopsy based on serum androgen
      levels. This study included 253 Japanese patients who underwent prostate biopsy
      at our institution. TT and FT, %FT (=FT/TT), age, PSA, prostate volume (PV) and
      PSA density (PSAD = PSA/PV) were assessed for association with prostate biopsy
      findings. The following results were obtained. Of 253 patients, 145 (57.3%) had
      positive biopsies. Compared to the negative biopsy group, the positive biopsy
      group demonstrated higher age, PSA and PSAD but lower PV, FT and %FT by
      univariate analysis. Multivariate logistic regression analysis indicated PSA,
      PSAD and %FT were independent predictors of cancer detection. We developed a
      predictive model based on PSAD and %FT, for which the area under the curve was
      significantly greater than that of PSA (0.82 vs 0.66), a well-known predictor.
      Applying this analysis to the subset of patients with PSA <10 ng/mL yielded
      similar results. We confirmed the utility of this model in another independent
      cohort of 88 patients. In conclusion, lower %FT predicted a positive prostate
      biopsy. We constructed a predictive model based on %FT and PSAD, which are easily
      obtained prior to biopsy.

PMID- 29046290
TI  - Re-Establishing Brain Networks in Patients with ESRD after Successful Kidney
      Transplantation.
AB  - BACKGROUND AND OBJECTIVES: Cognition in ESRD may be improved by kidney
      transplantation, but mechanisms are unclear. We explored patterns of resting
      state networks with resting-state functional magnetic resonance imaging among
      patients with ESRD before and after kidney transplantation. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Thirty-seven patients with ESRD scheduled for
      kidney transplantation and 22 age-, sex-, and education-matched healthy subjects
      underwent resting-state functional magnetic resonance imaging. Patients were
      imaged before and 1 and 6 months after kidney transplantation. Functional
      connectivity of seven resting-state subnetworks was evaluated: default mode
      network, dorsal attention network, central executive network, self-referential
      network, sensorimotor network, visual network, and auditory network. Mixed
      effects models tested associations of ESRD, kidney transplantation, and
      neuropsychological measurements with functional connectivity. RESULTS: Compared
      with controls, pretransplant patients showed abnormal functional connectivity in
      six subnetworks. Compared with pretransplant patients, increased functional
      connectivity was observed in the default mode network, the dorsal attention
      network, the central executive network, the sensorimotor network, the auditory
      network, and the visual network 1 and 6 months after kidney transplantation
      (P=0.01). Six months after kidney transplantation, no significant difference in
      functional connectivity was observed for the dorsal attention network, the
      central executive network, the auditory network, or the visual network between
      patients and controls. Default mode network and sensorimotor network remained
      significantly different from those in controls when assessed 6 months after
      kidney transplantation. A relationship between functional connectivity and
      neuropsychological measurements was found in specific brain regions of some brain
      networks. CONCLUSIONS: The recovery patterns of resting-state subnetworks vary
      after kidney transplantation. The dorsal attention network, the central executive
      network, the auditory network, and the visual network recovered to normal levels,
      whereas the default mode network and the sensorimotor network did not recover
      completely 6 months after kidney transplantation. Neural resting-state functional
      connectivity was lower among patients with ESRD compared with control subjects,
      but it significantly improved with kidney transplantation. Resting-state
      subnetworks exhibited variable recovery, in some cases to levels that were no
      longer significantly different from those of normal controls.

PMID- 29046291
TI  - Diabetic Kidney Disease.

PMID- 29046292
TI  - Identification of UT-A1- and AQP2-interacting proteins in rat inner medullary
      collecting duct.
AB  - The urea channel UT-A1 and the water channel aquaporin-2 (AQP2) mediate
      vasopressin-regulated transport in the renal inner medullary collecting duct
      (IMCD). To identify the proteins that interact with UT-A1 and AQP2 in native rat
      IMCD cells, we carried out chemical cross-linking followed by detergent
      solubilization, immunoprecipitation, and LC-MS/MS analysis of the
      immunoprecipitated material. The analyses revealed 133 UT-A1-interacting proteins
      and 139 AQP2-interacting proteins, each identified in multiple replicates. Fifty
      three proteins that were present in both the UT-A1 and the AQP2 interactomes can
      be considered as mediators of housekeeping interactions, likely common to all
      plasma membrane proteins. Among proteins unique to the UT-A1 list were those
      involved in posttranslational modifications: phosphorylation (protein kinases
      Cdc42bpb, Phkb, Camk2d, and Mtor), ubiquitylation/deubiquitylation (Uba1, Usp9x),
      and neddylation (Nae1 and Uba3). Among the proteins unique to the AQP2 list were
      several Rab proteins (Rab1a, Rab2a, Rab5b, Rab5c, Rab7a, Rab11a, Rab11b, Rab14,
      Rab17) involved in membrane trafficking. UT-A1 was found to interact with UT-A3,
      although quantitative proteomics revealed that most UT-A1 molecules in the cell
      are not bound to UT-A3. In vitro incubation of UT-A1 peptides with the protein
      kinases identified in the UT-A1 interactome revealed that all except Mtor were
      capable of phosphorylating known sites in UT-A1. Overall, the UT-A1 and AQP2
      interactomes provide a snapshot of a dynamic process in which UT-A1 and AQP2 are
      produced in the rough endoplasmic reticulum, processed through the Golgi
      apparatus, delivered to endosomes that move into and out of the plasma membrane,
      and are regulated in the plasma membrane.

PMID- 29046294
TI  - Local Ca2+ coupling between mitochondria and sarcoplasmic reticulum following
      depolarization in guinea pig urinary bladder smooth muscle cells.
AB  - Spatiotemporal changes in cytosolic Ca2+ concentration ([Ca2+]c) trigger a number
      of physiological functions in smooth muscle cells (SMCs). We previously imaged
      Ca2+-induced Ca2+ release following membrane depolarization as local Ca2+
      transients, Ca2+ hotspots, in subplasmalemmal regions. In this study, the
      physiological significance of mitochondria on local Ca2+ signaling was examined.
      Cytosolic and mitochondrial Ca2+ images following depolarization or action
      potentials were recorded in single SMCs from the guinea pig urinary bladder using
      a fast-scanning confocal fluorescent microscope. Depolarization- and action
      potential-induced [Ca2+]c transients occurred at several discrete sites in
      subplasmalemmal regions, peaked within 30 ms, and then spread throughout the
      whole-cell. In contrast, Ca2+ concentration in the mitochondria matrix ([Ca2+]m)
      increased after a delay of ~50 ms from the start of depolarization, and then
      peaked within 500 ms. Following repolarization, [Ca2+]c returned to the resting
      level with a half-decay time of ~500 ms, while [Ca2+]m recovered more slowly
      (~1.5 s). Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, a mitochondrial
      uncoupler, abolished depolarization-induced [Ca2+]m elevations and slowed [Ca2+]c
      changes. Importantly, short depolarization-induced changes in [Ca2+]m and
      transmembrane potential in mitochondria coupled to Ca2+ hotspots were
      significantly larger than those in other mitochondria. Total internal reflection
      fluorescence imaging revealed that a subset of mitochondria closely localized
      with ryanodine receptors and voltage-dependent Ca2+ channels. These results
      indicate that particular mitochondria are functionally coupled to ion channels
      and sarcoplasmic reticulum fragments within the local Ca2+ microdomain, and thus,
      strongly contribute to [Ca2+]c regulation in SMCs.

PMID- 29046293
TI  - Exercise induces TFEB expression and activity in skeletal muscle in a PGC-1alpha
      dependent manner.
AB  - The mitochondrial network in muscle is controlled by the opposing processes of
      mitochondrial biogenesis and mitophagy. The coactivator peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (PGC-1alpha) regulates biogenesis,
      while the transcription of mitophagy-related genes is controlled by transcription
      factor EB (TFEB). PGC-1alpha activation is induced by exercise; however, the
      effect of exercise on TFEB is not fully known. We investigated the interplay
      between PGC-1alpha and TFEB on mitochondria in response to acute contractile
      activity in C2C12 myotubes and following exercise in wild-type and PGC-1alpha
      knockout mice. TFEB nuclear localization was increased by 1.6-fold following 2 h
      of acute myotube contractile activity in culture, while TFEB transcription was
      also simultaneously increased by twofold to threefold. Viral overexpression of
      TFEB in myotubes increased PGC-1alpha and cytochrome- c oxidase-IV gene
      expression. In wild-type mice, TFEB translocation to the nucleus increased 2.4
      fold in response to acute exercise, while TFEB transcription, assessed through
      the electroporation of a TFEB promoter construct, was elevated by fourfold. These
      exercise effects were dependent on the presence of PGC-1alpha. Our data indicate
      that acute exercise provokes TFEB expression and activation in a PGC-1alpha
      dependent manner and suggest that TFEB, along with PGC-1alpha, is an important
      regulator of mitochondrial biogenesis in muscle as a result of exercise.

PMID- 29046295
TI  - Free circulating active elastase contributes to chronic inflammation in patients
      on hemodialysis.
AB  - Atherosclerosis and cardiovascular complications are prevalent among patients
      undergoing chronic hemodialysis (HD). In this population, peripheral
      polymorphonuclear leukocytes (PMNLs) are primed, releasing proinflammatory
      mediators such as elastase. Elastase is normally inhibited by a specific
      inhibitor, avoiding undesirable degradation of cellular and extracellular
      components. This study tested the hypothesis that in states of noninfectious
      inflammation, elastase is released by PMNLs and acts in an uncontrolled manner to
      inflict vascular damage. Blood was collected from patients undergoing HD and
      healthy controls (HC). PMNL intracellular and surface expressions of elastase
      were determined by quantitative real-time PCR, Western blotting, and flow
      cytometry. The elastase activity was evaluated using a fluorescent substrate. The
      levels of serum alpha1-antitrypsin (alpha1-AT), the natural elastase inhibitor,
      were determined by Western blot. Free active elastase was elevated in HD sera,
      whereas the levels of alpha1-AT were decreased compared with HC. The levels of
      the intracellular elastase enzyme and its activity were lower in HD PMNLs despite
      similar expression levels of elastase mRNA. Elastase binding to PMNL cell surface
      was higher in HD compared with HC. The increased circulating levels of free
      active elastase released from primed HD PMNLs together with the higher cell
      surface-bound enzymes and the lower levels of alpha1-AT result in the higher
      elastase activity in HD sera. This exacerbated elastase activity could lead to
      the endothelial dysfunction, as hypothesized. In addition, it suggests that free
      circulating elastase can serve as a new biomarker and therapeutic target to
      reduce inflammation and vascular complications in patients on hemodialysis.

PMID- 29046296
TI  - Geraniin is a diuretic by inhibiting the Na+-K+-2Cl- cotransporter NKCC2.
AB  - Geranium seemannii Peyr is a perennial plant endemic to central Mexico that has
      been widely used for its diuretic effect, but the responsible compound of this
      effect is unknown as well as the mechanism by which the diuretic effect is
      achieved. Geraniin is one of the compounds isolated from this kind of geranium.
      This study was designed to determinate whether geraniin possesses diuretic
      activity and to elucidate the mechanism of action. Geraniin was extracted and
      purified from Geranium seemannii Peyr. Male Wistar rats were divided into four
      groups: 1) Control, 2) 75 mg/kg of geraniin, 3) 20 mg/kg of furosemide, and 4) 10
      mg/kg of hydrochlorothiazide. Each treatment was administered by gavage every 24
      h for 7 days. The urinary excretion of electrolytes and the fractional excretion
      of sodium (FENa) were determined. To uncover the molecular target of geraniin,
      Xenopus laevis oocytes were microinjected with cRNAs encoding the Na+-Cl-
      cotransporter (NCC) and the Na+-K+-2Cl- cotransporter NKCC2 to functionally
      express these cotransporters. Geraniin significantly increased diuresis,
      natriuresis, and calciuresis to a similar extent as was observed in the
      furosemide-treated rats. Consistent with the furosemide-like effect, in X. laevis
      oocytes, geraniin significantly reduced the activity of NKCC2, with no effect on
      NCC activity. In contrast to furosemide, the effect of geraniin on NKCC2 was
      irreversible, apparently due to its inhibitory effect on heat shock protein 90.
      Our observations suggest that geraniin could have a potential role in the
      treatment of hypertension or edematous states.

PMID- 29046297
TI  - Renal and colonic potassium transporters in the pregnant rat.
AB  - Gestational potassium retention, most of which occurs during late pregnancy, is
      essential for fetal development. The purpose of this study was to examine
      mechanisms underlying changes in potassium handling by the kidney and colon in
      pregnancy. We found that potassium intake and renal excretion increased in late
      pregnancy while fecal potassium excretion remained unchanged and that pregnant
      rats exhibited net potassium retention. By quantitative PCR we found markedly
      increased H+-K+-ATPase type 2 (HKA2) mRNA expression in the cortex and outer
      medullary of late pregnant vs. virgin. Renal outer medullary potassium channel
      (ROMK) mRNA was unchanged in the cortex, but apical ROMK abundance (by
      immunofluorescence) was decreased in pregnant vs. virgin in the distal convoluted
      tubule (DCT) and connecting tubule (CNT). Big potassium-alpha (BKalpha) channel
      alpha protein abundance in intercalated cells in the cortex and outer medullary
      collecting ducts (by immunohistochemistry) fell in late pregnancy. In the distal
      colon we found increased HKA2 mRNA and protein abundance (Western blot) and
      decreased BKalpha protein with no observed changes in mRNA. Therefore, the
      potassium retention of pregnancy is likely to be due to increased collecting duct
      potassium reabsorption (via increased HKA2), decreased potassium secretion (via
      decreased ROMK and BK), as well as increased colonic reabsorption via HKA2.

PMID- 29046298
TI  - Identification of dual mechanisms mediating 5-hydroxytryptamine receptor 1F
      induced mitochondrial biogenesis.
AB  - Our laboratory recently made the novel observation that 5-hydroxytryptamine 1F (5
      HT1F) receptor activation induces mitochondrial biogenesis (MB), the production
      of new, functional mitochondria, in vitro and in vivo. We sought to determine the
      mechanism linking the 5-HT1F receptor to MB in renal proximal tubule cells. Using
      LY344864 , a selective 5-HT1F receptor agonist, we determined that the 5-HT1F
      receptor is coupled to Galphai/o and induces MB through Gbetagamma-dependent
      activation of Akt, endothelial nitric oxide synthase (eNOS), cyclic guanosine
      monophosphate (cGMP), protein kinase G (PKG), and peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (PGC-1alpha). We also report that the
      5-HT1F receptor signals through a second, Gbetagamma-dependent pathway that is
      linked by Akt phosphorylation of Raf. In contrast to the activated Akt pathway,
      Raf phosphorylation reduced extracellular signal regulated kinases (ERK1/2) and
      foxhead box O3a (FOXO3a) phosphorylation, suppressing an inhibitory MB pathway.
      These results demonstrate that the 5-HT1F receptor regulates MB through
      Gbetagamma-dependent dual mechanisms that activate a stimulatory MB pathway,
      Akt/eNOS/cGMP/PKG/PGC-1alpha, while simultaneously repressing an inhibitory MB
      pathway, Raf/MEK/ERK/FOXO3a. Novel mechanisms of MB provide the foundation for
      new chemicals that induce MB to treat acute and chronic organ injuries.

PMID- 29046299
TI  - High-content screening assay-based discovery of paullones as novel podocyte
      protective agents.
AB  - Podocyte dysfunction and loss is an early event and a hallmark of proteinuric
      kidney diseases. A podocyte's normal function is maintained via its unique
      cellular architecture that relies on an intracellular network of filaments,
      including filamentous actin (F-actin) and microtubules, that provides mechanical
      support. Damage to this filamentous network leads to changes in cellular
      morphology and results in podocyte injury, dysfunction, and death. Conversely,
      stabilization of this network protects podocytes and ameliorates proteinuria.
      This suggests that stabilization of podocyte architecture via its filamentous
      network could be a key therapeutic strategy for proteinuric kidney diseases.
      However, development of podocyte-directed therapeutics, especially those that
      target the cell's filamentous network, is still lacking, partly because of
      unavailability of appropriate cellular assays for use in a drug discovery
      environment. Here, we describe a new high-content screening-based methodology and
      its implementation on podocytes to identify paullone derivatives as a novel group
      of podocyte-protective compounds. We find that three compounds, i.e.,
      kenpaullone, 1-azakenpaullone, and alsterpaullone, dose dependently protect
      podocytes from puromycin aminonucleoside (PAN)-mediated injury in vitro by
      reducing PAN-induced changes in both the filamentous actin and microtubules, with
      alsterpaullone providing maximal protection. Mechanistic studies further show
      that alsterpaullone suppressed PAN-induced activation of signaling downstream of
      GSK3beta and p38 mitogen-activated protein kinase. In vivo it reduced ADR-induced
      glomerular injury in a zebrafish model. Together, these results identify paullone
      derivatives as novel podocyte-protective agents for future therapeutic
      development.

PMID- 29046300
TI  - Manganese promotes intracellular accumulation of AQP2 via modulating F-actin
      polymerization and reduces urinary concentration in mice.
AB  - Aquaporin-2 (AQP2) is a water channel protein expressed in principal cells (PCs)
      of the kidney collecting ducts (CDs) and plays a critical role in mediating water
      reabsorption and urine concentration. AQP2 undergoes both regulated trafficking
      mediated by vasopressin (VP) and constitutive recycling, which is independent of
      VP. For both pathways, actin cytoskeletal dynamics is a key determinant of AQP2
      trafficking. We report here that manganese chloride (MnCl2) is a novel and potent
      regulator of AQP2 trafficking in cultured cells and in the kidney. MnCl2
      treatment promoted internalization and intracellular accumulation of AQP2. The
      effect of MnCl2 on the intracellular accumulation of AQP2 was associated with
      activation of RhoA and actin polymerization without modification of AQP2
      phosphorylation. Although the level of total and phosphorylated AQP2 did not
      change, MnCl2 treatment impeded VP-induced phosphorylation of AQP2 at its serine
      256, -264, and -269 residues and dephosphorylation at serine 261. In addition,
      MnCl2 significantly promoted F-actin polymerization along with downregulation of
      RhoA activity and prevented VP-induced membrane accumulation of AQP2. Finally,
      MnCl2 treatment in mice resulted in significant polyuria and reduced urinary
      concentration, likely due to intracellular relocation of AQP2 in the PCs of
      kidney CDs. More importantly, the reduced urinary concentration caused by MnCl2
      treatment in animals was not corrected by VP. In summary, our study identified a
      novel effect of MnCl2 on AQP2 trafficking through modifying RhoA activity and
      actin polymerization and uncovered its potent impact on water diuresis in vivo.

PMID- 29046301
TI  - Bone mineral density during pregnancy in women participating in a randomized
      controlled trial of vitamin D supplementation.
AB  - Background: Little is known about bone mineral density (BMD) during pregnancy.
      Advances in technology with lower radiation emissions by dual-energy X-ray
      absorptiometry instruments now permit the safe measurement of BMD during
      pregnancy.Objective: We evaluated maternal BMD during pregnancy as a function of
      vitamin D status in women of diverse racial/ethnic backgrounds.Design: A total of
      301 women who underwent BMD measurements at 12-20 wk of gestation and again at 0
      14 wk postpartum were included in this analysis. Women were a subset of subjects
      who were recruited for a randomized, controlled, double-blind trial of vitamin D
      supplementation in pregnancy (400, 2000, or 4000 IU/d).Results: Treatment had no
      significant effect on changes in BMD that occurred between 12-20 wk of gestation
      and 0-14 wk postpartum. Similarly, changes in spine and femoral neck bone mineral
      contents (BMCs) were not significantly different in the treatment groups. In
      addition, vitamin D inadequacy (serum 25-hydroxyvitamin D concentration, averaged
      across pregnancy, <50 nmol/L) was not associated with changes in BMD or BMC.
      There were significant racial/ethnic differences in spine BMD. African Americans
      lost more spine BMD than did Caucasians (-0.04 +/- 0.04 compared with -0.02 +/-
      0.04 g/cm2; P = 0.033). In addition, baseline obesity was associated with a
      greater loss of femoral neck BMD. The means +/- SDs of femoral neck BMD loss were
      -0.02 +/- 0.05 and 0.0 +/- 0.03 g/cm2 for groups with baseline body mass index
      (BMI; in kg/m2) >=30 and <30, respectively.Conclusion: These findings do not
      support a dose effect of vitamin D supplementation on bone health and suggest
      that race/ethnicity and BMI play an important role in pregnancy bone health. This
      trial was registered at clinicaltrials.gov as NCT00292591.

PMID- 29046302
TI  - A 1-h time interval between a meal containing iron and consumption of tea
      attenuates the inhibitory effects on iron absorption: a controlled trial in a
      cohort of healthy UK women using a stable iron isotope.
AB  - Background: Tea has been shown to be a potent inhibitor of nonheme iron
      absorption, but it remains unclear whether the timing of tea consumption relative
      to a meal influences iron bioavailability.Objective: The aim of the study was to
      investigate the effect of a 1-h time interval of tea consumption on nonheme iron
      absorption in an iron-containing meal in a cohort of iron-replete, nonanemic
      female subjects with the use of a stable isotope (57Fe).Design: Twelve women
      (mean +/- SD age: 24.8 +/- 6.9 y) were administered a standardized porridge meal
      extrinsically labeled with 4 mg 57Fe as FeSO4 on 3 separate occasions, with a 14
      d time interval between each test meal (TM). The TM was administered with water
      (TM-1), with tea administered simultaneously (TM-2), and with tea administered 1
      h postmeal (TM-3). Fasted venous blood samples were collected for iron isotopic
      analysis and measurement of iron status biomarkers. Fractional iron absorption
      was estimated by the erythrocyte iron incorporation method.Results: Iron
      absorption was 5.7% +/- 8.5% (TM-1), 3.6% +/- 4.2% (TM-2), and 5.7% +/- 5.4% (TM
      3). Mean fractional iron absorption was found to be significantly higher (2.2%)
      when tea was administered 1 h postmeal (TM-3) than when tea was administered
      simultaneously with the meal (TM-2) (P = 0.046). An ~50% reduction in the
      inhibitory effect of tea (relative to water) was observed, from 37.2% (TM-2) to
      18.1% (TM-3).Conclusions: This study shows that tea consumed simultaneously with
      an iron-containing porridge meal leads to decreased nonheme iron absorption and
      that a 1-h time interval between a meal and tea consumption attenuates the
      inhibitory effect, resulting in increased nonheme iron absorption. These findings
      are not only important in relation to the management of iron deficiency but
      should also inform dietary advice, especially that given to those at risk of
      deficiency. This trial was registered at clinicaltrials.gov as NCT02365103.

PMID- 29046303
TI  - Salt substitution is a promising but unproven intervention for stroke management.

PMID- 29046304
TI  - Comparison among criteria to define successful weight-loss maintainers and
      regainers in the Action for Health in Diabetes (Look AHEAD) and Diabetes
      Prevention Program trials.
AB  - Background: Given the low rates of successful weight maintenance after lifestyle
      induced weight loss, it is critical to develop approaches that distinguish
      successful weight-loss maintainers from regainers.Objective: The aim of this
      study was to compare published categorization criteria that differentiate
      maintainers and regainers via quantitative agreement.Design: The study used
      publicly available data from Look AHEAD (Action for Health in Diabetes; n = 1791)
      and Diabetes Prevention Program (DPP; n = 613) participants with >=3% initial
      weight loss after lifestyle interventions and 4-y follow-up data. Eight
      previously published criteria defining maintainers and regainers were compared
      with respect to number of participants and concordance via agreement statistics.
      Criteria were assessed separately among those with 3-9% and >=10% initial weight
      loss.Results: Regainers had higher body weight at year 4 than did maintainers
      (mean difference range: 6.6-11.9 kg in Look AHEAD; 11.5-14.6 kg in DPP; P <
      0.0001). Assessing concordance among criteria, agreement was dependent on initial
      weight loss. Among those with 3-9% initial weight loss in both cohorts, 9 of 28
      comparisons were concordant (agreement >=80%). Among those with >=10% initial
      weight loss, 7 of 28 comparisons in Look AHEAD and 13 of 28 in the DPP were in
      high agreement. The definition of successful weight-loss maintenance "regaining
      <=25% of initial weight loss during maintenance" showed high agreement with the
      most commonly used definition of "staying >=10% below initial weight" among those
      with >=10% initial weight loss (agreement: 85.0% in Look AHEAD; 87.4% in DPP).
      The same definition of <=25% regain showed high agreement with the definition of
      staying >=5% below initial weight among those with 3-9% initial weight loss
      (agreement: 91.6% in Look AHEAD; 90.5% in DPP).Conclusions: Although all of the
      criteria discriminated on the basis of weight loss, many showed low agreement,
      which limited cross-study comparisons. Among criteria with high agreement, the
      definition of successful weight maintenance "regaining <=25% of initial weight
      loss during maintenance" is a preferred definition of success, given the
      realistic challenges of maintaining 100% weight loss and flexible application in
      populations with high initial weight-loss variations. This trial was registered
      at clinicaltrials.gov as NCT00017953 (Look AHEAD) and NCT00004992 (DPP).

PMID- 29046305
TI  - Neuromodulation directed at the prefrontal cortex of subjects with obesity
      reduces snack food intake and hunger in a randomized trial.
AB  - Background: Obesity is associated with reduced activation in the left
      dorsolateral prefrontal cortex (DLPFC), a region of the brain that plays a key
      role in the support of self-regulatory aspects of eating behavior and inhibitory
      control. Transcranial direct current stimulation (tDCS) is a noninvasive
      technique used to modulate brain activity.Objectives: We tested whether repeated
      anodal tDCS targeted at the left DLPFC (compared with sham tDCS) has an immediate
      effect on eating behavior during ad libitum food intake, resulting in weight
      change, and whether it might influence longer-term food intake-related appetite
      ratings in individuals with obesity.Design: In a randomized parallel-design study
      combining inpatient and outpatient assessments over 31 d, 23 individuals with
      obesity [12 men; mean +/- SD body mass index (BMI; in kg/m2): 39.3 +/- 8.42]
      received 15 sessions of anodal (i.e., enhancing cortical activity) or sham tDCS
      aimed at the left DLPFC. Ad libitum food intake was assessed through the use of a
      vending machine paradigm and snack food taste tests (SFTTs). Appetite was
      evaluated with a visual analog scale (VAS). Body weight was measured. We examined
      the effect of short-term (i.e., 3 sessions) and long-term (i.e., 15 sessions)
      tDCS on these variables.Results: Relative to sham tDCS, short-term anodal tDCS
      did not influence ad libitum intake of food from the vending machines.
      Accordingly, no effect on short-term or 4-wk weight change was observed. In the
      anodal tDCS group, compared with the sham group, VAS ratings for hunger and the
      urge to eat declined significantly more (P = 0.01 and P = 0.05, respectively),
      and total energy intake during an SFTT was relatively lower in satiated
      individuals (P = 0.01), after long-term tDCS.Conclusions: Short-term anodal tDCS
      of the left DLPFC did not have an immediate effect on ad libitum food intake or
      thereby weight change, relative to sham tDCS. Hunger and snack food intake were
      reduced only after a longer period of anodal tDCS in individuals with obesity.
      This trial was registered at clinicaltrials.gov as NCT00739362.

PMID- 29046306
TI  - GI-19007, a Novel Saccharomyces cerevisiae-Based Therapeutic Vaccine against
      Tuberculosis.
AB  - As yet, very few vaccine candidates with activity in animals against
      Mycobacterium tuberculosis infection have been tested as therapeutic postexposure
      vaccines. We recently described two pools of mycobacterial proteins with this
      activity, and here we describe further studies in which four of these proteins
      (Rv1738, Rv2032, Rv3130, and Rv3841) were generated as a fusion polypeptide and
      then delivered in a novel yeast-based platform (Tarmogen) which itself has
      immunostimulatory properties, including activation of Toll-like receptors. This
      platform can deliver antigens into both the class I and class II antigen
      presentation pathways and stimulate strong Th1 and Th17 responses. In mice this
      fusion vaccine, designated GI-19007, was immunogenic and elicited strong gamma
      interferon (IFN-gamma) and interleukin-17 (IL-17) responses; despite this, they
      displayed minimal prophylactic activity in mice that were subsequently infected
      with a virulent clinical strain. In contrast, in a therapeutic model in the
      guinea pig, GI-19007 significantly reduced the lung bacterial load and reduced
      lung pathology, particularly in terms of secondary lesion development, while
      significantly improving survival in one-third of these animals. In further
      studies in which guinea pigs were vaccinated with BCG before challenge,
      therapeutic vaccination with GI-19007 initially improved survival versus that of
      animals given BCG alone, although this protective effect was gradually lost at
      around 400 days after challenge. Given its apparent ability to substantially
      limit bacterial dissemination within and from the lungs, GI-19007 potentially can
      be used to limit lung damage as well as facilitating chemotherapeutic regimens in
      infected individuals.

PMID- 29046307
TI  - High-Definition Mapping of Four Spatially Distinct Neutralizing Epitope Clusters
      on RiVax, a Candidate Ricin Toxin Subunit Vaccine.
AB  - RiVax is a promising recombinant ricin toxin A subunit (RTA) vaccine antigen that
      has been shown to be safe and immunogenic in humans and effective at protecting
      rhesus macaques against lethal-dose aerosolized toxin exposure. We previously
      used a panel of RTA-specific monoclonal antibodies (MAbs) to demonstrate, by
      competition enzyme-linked immunosorbent assay (ELISA), that RiVax elicits similar
      serum antibody profiles in humans and macaques. However, the MAb binding sites on
      RiVax have yet to be defined. In this study, we employed hydrogen exchange-mass
      spectrometry (HX-MS) to localize the epitopes on RiVax recognized by nine toxin
      neutralizing MAbs and one nonneutralizing MAb. Based on strong protection from
      hydrogen exchange, the nine MAbs grouped into four spatially distinct epitope
      clusters (namely, clusters I to IV). Cluster I MAbs protected RiVax's alpha-helix
      B (residues 94 to 107), a protruding immunodominant secondary structure element
      known to be a target of potent toxin-neutralizing antibodies. Cluster II
      consisted of two subclusters located on the "back side" (relative to the active
      site pocket) of RiVax. One subcluster involved alpha-helix A (residues 14 to 24)
      and alpha-helices F-G (residues 184 to 207); the other encompassed beta-strand d
      (residues 62 to 69) and parts of alpha-helices D-E (154 to 164) and the
      intervening loop. Cluster III involved alpha-helices C and G on the front side of
      RiVax, while cluster IV formed a sash from the front to back of RiVax, spanning
      strands b, c, and d (residues 35 to 59). Having a high-resolution B cell epitope
      map of RiVax will enable the development and optimization of competitive serum
      profiling assays to examine vaccine-induced antibody responses across species.

PMID- 29046308
TI  - Progress toward Development of a Vaccine against Congenital Cytomegalovirus
      Infection.
AB  - A vaccine against congenital human cytomegalovirus (CMV) infection is a major
      public health priority. Congenital CMV causes substantial long-term morbidity,
      particularly sensorineural hearing loss (SNHL), in newborns, and the public
      health impact of this infection on maternal and child health is underrecognized.
      Although progress toward development of a vaccine has been limited by an
      incomplete understanding of the correlates of protective immunity for the fetus,
      knowledge about some of the key components of the maternal immune response
      necessary for preventing transplacental transmission is accumulating. Moreover,
      although there have been concerns raised about observations indicating that
      maternal seropositivity does not fully prevent recurrent maternal CMV infections
      during pregnancy, it is becoming increasing clear that preconception immunity
      does confer some measure of protection against both CMV transmission and CMV
      disease (if transmission occurs) in the newborn infant. Although the immunity to
      CMV conferred by both infection and vaccination is imperfect, there are
      encouraging data emerging from clinical trials demonstrating the immunogenicity
      and potential efficacy of candidate CMV vaccines. In the face of the knowledge
      that between 20,000 and 30,000 infants are born with congenital CMV in the United
      States every year, there is an urgent and compelling need to accelerate the pace
      of vaccine trials. In this minireview, we summarize the status of CMV vaccines in
      clinical trials and provide a perspective on what would be required for a CMV
      immunization program to become incorporated into clinical practice.

PMID- 29046310
TI  - Protein Structure Facilitates High-Resolution Immunological Mapping.
AB  - Select agents (SA) pose unique challenges for licensing vaccines and therapies.
      In the case of toxin-mediated diseases, HHS assigns guidelines for SA use,
      oversees vaccine and therapy development, and approves animal models and
      approaches to identify mechanisms for toxin neutralization. In this commentary,
      we discuss next-generation vaccines and therapies against ricin toxin and
      botulinum toxin, which are regulated SA toxins that utilize structure-based
      approaches for countermeasures to guide rapid response to future biothreats.

PMID- 29046309
TI  - Stable Chromosomal Expression of Shigella flexneri 2a and 3a O-Antigens in the
      Live Salmonella Oral Vaccine Vector Ty21a.
AB  - We have been exploring the use of the live attenuated Salmonella enterica serovar
      Typhi Ty21a vaccine strain as a versatile oral vaccine vector for the expression
      and delivery of multiple foreign antigens, including Shigella O-antigens. In this
      study, we separately cloned genes necessary for the biosynthesis of the Shigella
      flexneri serotype 2a and 3a O-antigens, which have been shown to provide broad
      cross-protection to multiple disease-predominant S. flexneri serotypes. The
      cloned S. flexneri 2a rfb operon, along with bgt and gtrII, contained on the SfII
      bacteriophage, was sufficient in Ty21a to express the heterologous S. flexneri 2a
      O-antigen containing the 3,4 antigenic determinants. Further, this rfb operon,
      along with gtrA, gtrB, and gtrX contained on the Sfx bacteriophage and oac
      contained on the Sf6 bacteriophage, was sufficient to express S. flexneri 3a O
      antigen containing the 6, 7, and 8 antigenic determinants. Ty21a, with these
      plasmid-carried or chromosomally inserted genes, demonstrated simultaneous and
      stable expression of homologous S Typhi O-antigen plus the heterologous S.
      flexneri O-antigen. Candidate Ty21a vaccine strains expressing heterologous S.
      flexneri 2a or 3a lipopolysaccharide (LPS) elicited significant serum antibody
      responses against both homologous S Typhi and heterologous Shigella LPS and
      protected mice against virulent S. flexneri 2a or 3a challenges. These new S.
      flexneri 2a and 3a O-antigen-expressing Ty21a vaccine strains, together with our
      previously constructed Ty21a strains expressing Shigella sonnei or Shigella
      dysenteriae 1 O-antigens, have the potential to be used together for simultaneous
      protection against the predominant causes of shigellosis worldwide as well as
      against typhoid fever.

PMID- 29046311
TI  - Activity of muscle sympathetic neurons during normotensive pregnancy.
AB  - In pathological populations, elevated sympathetic activity is associated with
      increased activity of individual sympathetic neurons. We used custom action
      potential detection software to analyze multiunit sympathetic activity in 18
      normotensive pregnant women (third trimester; 33 +/- 5 wk) and 19 nonpregnant
      women at rest and a subset (10 and 13, respectively) during a cold pressor
      challenge. Although the number of action potentials per burst and number of
      active amplitude-based "clusters" were not different between groups, the total
      number of sympathetic action potentials per minute was higher in pregnant women
      at rest. Individual clusters were active predominately once per burst, suggesting
      they represent single neurons. Action potentials occurred in closer succession in
      normotensive pregnant (interspike interval 36 +/- 10 ms) versus nonpregnant women
      (50 +/- 27 ms; P < 0.001) at rest. Pregnant women had a lower total peripheral
      resistance (11.7 +/- 3.0 mmHg.l-1.min) than nonpregnant women (15.1 +/- 2.7
      mmHg.l-1.min; P < 0.001), indicating a blunted neurovascular transduction. The
      cold pressor reduced the number of action potentials per burst in both groups due
      to shortening of the R-R interval in conjunction with increased burst frequency;
      total neural firing per minute was unchanged. Thus elevated sympathetic activity
      during normotensive pregnancy is specific to increased incidence of multiunit
      bursts. This is likely due to decreased central gating of burst output as opposed
      to generalized increases in central drive. These data also reinforce the concept
      that pregnancy appears to be the only healthy state of chronic sympathetic
      hyperactivity of which we are aware.

PMID- 29046312
TI  - Relaxin-mediated renal vasodilation in the rat is associated with falls in
      glomerular blood pressure.
AB  - Relaxin (RLX) is a pleiotropic peptide hormone with marked renal vasodilatory
      actions that are physiologically important during pregnancy. RLX also has potent
      antifibrotic actions and is being tested therapeutically in various fibrotic
      diseases, including chronic kidney disease (CKD). Since renal vasodilation may
      expose the glomerulus to increased blood pressure [glomerular capillary pressure
      (PGC)], which exacerbates progression of CKD, we assessed the glomerular
      hemodynamic actions of acute (0.89 ug.100 g body wt-1.h-1 iv over 75 min) and
      chronic (1.5 ug.100 g body wt-1.h-1 sc) administration of RLX. Both acute and
      chronic RLX produced marked renal vasodilation and increased renal plasma flow
      (RPF) in euvolemic, anesthetized male rats. Glomerular filtration rate also
      increased with RLX, but the magnitude of the rise was much less than the increase
      in RPF due to concomitant decreases in filtration fraction. The fall in
      filtration fraction was the result of significant decreases in PGC, despite a
      slight increase in mean arterial blood pressure (MAP) with acute RLX and no net
      change in MAP with chronic RLX. This fall in PGC occurred because of the "in
      series" arrangement of the afferent and efferent arteriolar resistance vessels,
      which can regulate PGC independently of MAP. With both acute and chronic RLX,
      efferent arteriolar resistance vessels relaxed to a greater extent than afferent
      arteriolar resistance vessels, thus producing falls in PGC. Based on this
      finding, RLX has a beneficial hemodynamic impact on the kidney, which, together
      with the antifibrotic actions of RLX, suggests a strong therapeutic potential for
      use in CKD.

PMID- 29046313
TI  - Dicarbonyl stress and glyoxalase enzyme system regulation in human skeletal
      muscle.
AB  - Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and
      may be exacerbated by protein modifications by methylglyoxal (MG), known as
      dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2
      (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein
      expression, activity, and regulation remain largely unexplored in skeletal
      muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase
      enzyme system in the skeletal muscle of subjects with T2DM (age: 56 +/- 5 yr.;
      BMI: 32 +/- 2 kg/m2) compared with lean healthy control subjects (LHC; age: 27 +/
      1 yr.; BMI: 22 +/- 1 kg/m2). Skeletal muscle biopsies obtained from the vastus
      lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU.m
      2.min-1)-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl
      stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress
      and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI,
      percent body fat, and HOMA-IR, while positively correlating with clamp-derived
      glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%),
      which is a positive regulator of GLO1, while Keap1 protein expression, a negative
      regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during
      the clamp had a differential effect on NRF2, Keap1, and MG-modified protein
      expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme
      system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle
      insulin resistance. Whether these phenotypic differences contribute to the
      development of T2DM warrants further investigation.

PMID- 29046314
TI  - Respiratory dysfunction following neonatal sustained hypoxia exposure during a
      critical window of brain stem extracellular matrix formation.
AB  - The extracellular matrix (ECM) modulates brain maturation and plays a major role
      in regulating neuronal plasticity during critical periods of development. We
      examined 1) whether there is a critical postnatal period of ECM expression in
      brain stem cardiorespiratory control regions and 2) whether the attenuated
      hypoxic ventilatory response (HVR) following neonatal sustained (5 days) hypoxia
      [SH (11% O2, 24 h/day)] exposure is associated with altered ECM formation. The
      nucleus tractus solitarius (nTS), dorsal motor nucleus of the vagus, hypoglossal
      motor nucleus, cuneate nucleus, and area postrema were immunofluorescently
      processed for aggrecan and Wisteria floribunda agglutinin (WFA), a key
      proteoglycan of the ECM and the perineuronal net. From postnatal day ( P) 5 (
      P5), aggrecan and WFA expression increased postnatally in all regions. We
      observed an abrupt increase in aggrecan expression in the nTS, a region that
      integrates and receives afferent inputs from the carotid body, between P10 and
      P15 followed by a distinct and transient plateau between P15 and P20. WFA
      expression in the nTS exhibited an analogous transient plateau, but it occurred
      earlier (between P10 and P15). SH between P11 and P15 attenuated the HVR
      (assessed at P16) and increased aggrecan (but not WFA) expression in the nTS,
      dorsal motor nucleus of the vagus, and area postrema. An intracisternal
      microinjection of chondroitinase ABC, an enzyme that digests chondroitin sulfate
      proteoglycans, rescued the HVR and the increased aggrecan expression. These data
      indicate that important stages of ECM formation take place in key brain stem
      respiratory neural control regions and appear to be associated with a heightened
      vulnerability to hypoxia.

PMID- 29046315
TI  - Sex differences in maternal gestational hypertension-induced sensitization of
      angiotensin II hypertension in rat offspring: the protective effect of estrogen.
AB  - Recent studies demonstrate that maternal hypertension during pregnancy sensitizes
      an angiotensin (ANG) II-induced increase in blood pressure (BP) in adult male
      offspring that was associated with upregulation of mRNA expression of several
      renin-angiotensin-aldosterone system (RAAS) components and NADPH oxidase in the
      lamina terminalis (LT) and paraventricular nucleus (PVN). The purpose of the
      present study was to test whether there are sex differences in the maternal
      hypertension-induced sensitization of ANG II hypertension, and whether sex
      hormones are involved in the sensitization process. Male offspring of
      hypertensive dams showed an enhanced hypertensive response to systemic ANG II
      when compared with male offspring of normotensive dams and to female offspring of
      either normotensive or hypertensive dams. Castration did not alter the
      hypertensive response to ANG II in male offspring. Intact female offspring had no
      upregulation of RAAS components and NADPH oxidase in the LT and PVN, whereas
      ovariectomy (OVX) upregulated mRNA expression of several RAAS components and
      NADPH oxidase in these nuclei and induced a greater increase in the pressor
      response to ANG II in female offspring of hypertensive dams compared with female
      offspring of normotensive dams. This enhanced increase in BP was partially
      attenuated by 17beta-estradiol replacement in the OVX offspring of hypertensive
      dams. The results suggest that maternal hypertension induces a sex-specific
      sensitization of ANG II-induced hypertension and mRNA expression of brain RAAS
      and NADPH oxidase in offspring. Female offspring are protected from maternal
      hypertension-induced sensitization of ANG II hypertension, and female sex
      hormones are partially responsible for this protective effect.

PMID- 29046316
TI  - Evidence for the presence in rainbow trout brain of amino acid-sensing systems
      involved in the control of food intake.
AB  - To assess the hypothesis of central amino acid-sensing systems involved in the
      control of food intake in fish, we carried out two experiments in rainbow trout.
      In the first one, we injected intracerebroventricularly two different branched
      chain amino acids (BCAAs), leucine and valine, and assessed food intake up to 48
      h later. Leucine decreased and valine increased food intake. In a second
      experiment, 6 h after similar intracerebroventricular treatment we determined
      changes in parameters related to putative amino acid-sensing systems. Different
      areas of rainbow trout brain present amino acid-sensing systems responding to
      leucine (hypothalamus and telencephalon) and valine (telencephalon), while other
      areas (midbrain and hindbrain) do not respond to these treatments. The decreased
      food intake observed in fish treated intracerebroventricularly with leucine could
      relate to changes in mRNA abundance of hypothalamic neuropeptides
      [proopiomelanocortin (POMC), cocaine- and amphetamine-related transcript (CART),
      neuropeptide Y (NPY), and agouti-related peptide (AgRP)]. These in turn could
      relate to amino acid-sensing systems present in the same area, related to BCAA
      and glutamine metabolism, as well as mechanistic target of rapamycin (mTOR),
      taste receptors, and general control nonderepressible 2 (GCN2) kinase signaling.
      The treatment with valine did not affect amino acid-sensing parameters in the
      hypothalamus. These responses are comparable to those characterized in mammals.
      However, clear differences arise when comparing rainbow trout and mammals, in
      particular with respect to the clear orexigenic effect of valine, which could
      relate to the finding that valine partially stimulated two amino acid-sensing
      systems in the telencephalon. Another novel result is the clear effect of leucine
      on telencephalon, in which amino acid-sensing systems, but not neuropeptides,
      were activated as in the hypothalamus.

PMID- 29046317
TI  - Vasoactivity of nitrite in the iliac artery of the toad Rhinella marina.
AB  - Nitrite ([Formula: see text]) causes vasodilation in mammals due to the formation
      of (nitric oxide) NO by endogenous [Formula: see text] reduction in the vascular
      wall. In this study, we determined if a similar mechanism operates in amphibians.
      Dual-wire myography of the iliac artery from Rhinella marina showed that applied
      [Formula: see text] caused a concentration-dependent vasodilation in normoxia
      (21% O2; EC50: 438 uM). Hypoxia (0.63% O2) significantly increased the maximal
      dilation to [Formula: see text] by 5% ( P = 0.0398). The addition of
      oxyhemoglobin significantly increased the EC50 ( P = 0.0144; EC50: 2,236 uM) but
      did not affect the maximal vasodilation. In contrast, partially deoxygenated
      hemoglobin (90% desaturation) did not affect the EC50 ( P = 0.1189) but
      significantly ( P = 0.0012) increased the maximal dilation to [Formula: see text]
      by 11%. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ) completely abolished the response to [Formula: see text]
      ( P < 0.0001), and of the nitric oxide synthase inhibitors, only N5-(1-imino-3
      butenyl)-l-ornithine (vinyl-l-NIO; P = 0.0028) significantly reduced the
      [Formula: see text] vasodilation. The xanthine oxidoreductase inhibitor
      allopurinol ( P = 0.927), the nitric oxide-scavenger 2-(4-carboxyphenyl)-4,5
      dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3-oxide (C-PTIO; P = 0.478), and
      disruption of the endothelium ( P = 0.094) did not affect the [Formula: see text]
      vasodilation. Incubation of iliac arteries with 1 mM [Formula: see text] did not
      a cause a change in the cGMP concentration (P = 0.407). Plasma [Formula: see
      text] was found to be 0.86 +/- 0.20 umol/l, while nitrate ([Formula: see text])
      was 19.55 +/- 2.55 umol/l. Both cygb and ngb mRNAs were expressed in the iliac
      artery, and it is possible that these globins facilitate [Formula: see text]
      reduction in hypoxia. In addition, [Formula: see text] intracellular
      disproportionation processes could be important in the generation of NO from
      [Formula: see text].

PMID- 29046318
TI  - Central serotonin and the control of arterial blood pressure and heart rate in
      infant rats: influence of sleep state and sex.
AB  - Sudden infant death syndrome (SIDS) is associated with serotonin (5-HT) neuron
      abnormalities. There is evidence of autonomic dysfunction during sleep in infants
      eventually succumbing to SIDS, as well as cardiovascular collapse before death.
      Neonatal rodents deficient in central 5-HT display hypotension and bradycardia.
      We hypothesized that central 5-HT reduces cardiac vagal tone and increases
      sympathetic vascular tone and, given the firing pattern of 5-HT neurons, that
      these effects are greater in quiet sleep (QS) than in active sleep (AS). We
      tested these hypotheses using 2-wk-old male and female rat pups lacking
      tryptophan hydroxylase-2 ( TPH2-/-) and wild-type (WT) littermates. Arterial
      blood pressure (ABP) and heart rate (HR) were measured over 3 h during periods of
      QS and AS. We also gave atropine or atenolol (each 1 mg/kg iv), or phentolamine
      (5, 50, and 500 MUg/kg iv) to separate groups to assess the effects 5-HT
      deficiency on autonomic tone to the heart or sympathetic vascular tone,
      respectively. Compared with WT, male and female TPH2-/- pups had reduced ABP in
      QS but not in AS. Atropine induced a greater HR increase in female TPH2-/- than
      in female WT pups, an effect absent in male TPH2-/- pups. Both genotypes
      experienced the same atenolol-induced drop in HR. In males only, phentolamine
      induced a smaller decrease in the ABP of TPH2-/- pups compared with WT. These
      data suggest that central 5-HT maintains ABP in QS, and HR in both states. In
      males, central 5-HT facilitates sympathetic vascular tone, and in females it
      reduces cardiac vagal drive.

PMID- 29046319
TI  - Effect of Intravenous Fentanyl on Ticagrelor Absorption and Platelet Inhibition
      Among Patients Undergoing Percutaneous Coronary Intervention: The PACIFY
      Randomized Clinical Trial (Platelet Aggregation With Ticagrelor Inhibition and
      Fentanyl).

PMID- 29046320
TI  - Mortality and Cerebrovascular Events After Heart Rhythm Disorder Management
      Procedures.
AB  - BACKGROUND: Recognition of rates and causes of hard, patient-centered outcomes of
      death and cerebrovascular events (CVEs) after heart rhythm disorder management
      (HRDM) procedures is an essential step for the development of quality improvement
      programs in electrophysiology laboratories. Our primary aim was to assess and
      characterize death and CVEs (stroke or transient ischemic attack) after HRDM
      procedures over a 17-year period. METHODS: We performed a retrospective cohort
      study of all patients undergoing HRDM procedures between January 2000 and
      November 2016 at the Mayo Clinic. Patients from all 3 tertiary academic centers
      (Rochester, Phoenix, and Jacksonville) were included in the study. All in
      hospital deaths and CVEs after HRDM procedures were identified and were further
      characterized as directly or indirectly related to the HRDM procedure. Subgroup
      analysis of death and CVE rates was performed for ablation, device implantation,
      electrophysiology study, lead extraction, and defibrillation threshold testing
      procedures. RESULTS: A total of 48 913 patients (age, 65.7+/-6.6 years; 64% male)
      who underwent a total of 62 065 HRDM procedures were included in the study. The
      overall mortality and CVE rates in the cohort were 0.36% (95% confidence interval
      [CI], 0.31-0.42) and 0.12% (95% CI, 0.09-0.16), respectively. Patients undergoing
      lead extraction had the highest overall mortality rate at 1.9% (95% CI, 1.34
      2.61) and CVE rate at 0.62% (95% CI, 0.32-1.07). Among patients undergoing HRDM
      procedures, 48% of deaths directly related to the HDRM procedure were among
      patients undergoing device implantation procedures. Overall, cardiac tamponade
      was the most frequent direct cause of death (40%), and infection was the most
      common indirect cause of death (29%). The overall 30-day mortality rate was
      0.76%, with the highest being in lead extraction procedures (3.08%), followed by
      device implantation procedures (0.94%). CONCLUSIONS: Half of the deaths directly
      related to an HRDM procedure were among the patients undergoing device
      implantation procedures, with cardiac tamponade being the most common cause of
      death. This highlights the importance of the development of protocols for the
      quick identification and management of cardiac tamponade even in procedures
      typically believed to be lower risk such as device implantation.

PMID- 29046321
TI  - Why we must defend suicide in fiction.

PMID- 29046322
TI  - Pumilio2-deficient mice show a predisposition for epilepsy.
AB  - Epilepsy is a neurological disease that is caused by abnormal hypersynchronous
      activities of neuronal ensembles leading to recurrent and spontaneous seizures in
      human patients. Enhanced neuronal excitability and a high level of synchrony
      between neurons seem to trigger these spontaneous seizures. The molecular
      mechanisms, however, regarding the development of neuronal hyperexcitability and
      maintenance of epilepsy are still poorly understood. Here, we show that pumilio
      RNA-binding family member 2 (Pumilio2; Pum2) plays a role in the regulation of
      excitability in hippocampal neurons of weaned and 5-month-old male mice. Almost
      complete deficiency of Pum2 in adult Pum2 gene-trap mice (Pum2 GT) causes
      misregulation of genes involved in neuronal excitability control. Interestingly,
      this finding is accompanied by the development of spontaneous epileptic seizures
      in Pum2 GT mice. Furthermore, we detect an age-dependent increase in Scn1a
      (Nav1.1) and Scn8a (Nav1.6) mRNA levels together with a decrease in Scn2a
      (Nav1.2) transcript levels in weaned Pum2 GT that is absent in older mice.
      Moreover, field recordings of CA1 pyramidal neurons show a tendency towards a
      reduced paired-pulse inhibition after stimulation of the Schaffer-collateral
      commissural pathway in Pum2 GT mice, indicating a predisposition to the
      development of spontaneous seizures at later stages. With the onset of
      spontaneous seizures at the age of 5 months, we detect increased protein levels
      of Nav1.1 and Nav1.2 as well as decreased protein levels of Nav1.6 in those mice.
      In addition, GABA receptor subunit alpha-2 (Gabra2) mRNA levels are increased in
      weaned and adult mice. Furthermore, we observe an enhanced GABRA2 protein level
      in the dendritic field of the CA1 subregion in the Pum2 GT hippocampus. We
      conclude that altered expression levels of known epileptic risk factors such as
      Nav1.1, Nav1.2, Nav1.6 and GABRA2 result in enhanced seizure susceptibility and
      manifestation of epilepsy in the hippocampus. Thus, our results argue for a role
      of Pum2 in epileptogenesis and the maintenance of epilepsy.

PMID- 29046323
TI  - European Society of Endocrinology Clinical Practice Guidelines for the management
      of aggressive pituitary tumours and carcinomas.
AB  - BACKGROUND: Pituitary tumours are common and easily treated by surgery or medical
      treatment in most cases. However, a small subset of pituitary tumours does not
      respond to standard medical treatment and presents with multiple local
      recurrences (aggressive pituitary tumours) and in rare occasion with metastases
      (pituitary carcinoma). The present European Society of Endocrinology (ESE)
      guideline aims to provide clinical guidance on diagnosis, treatment and follow-up
      in aggressive pituitary tumours and carcinomas. METHODS: We decided upfront,
      while acknowledging that literature on aggressive pituitary tumours and
      carcinomas is scarce, to systematically review the literature according to the
      GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
      The review focused primarily on first- and second-line treatment in aggressive
      pituitary tumours and carcinomas. We included 14 single-arm cohort studies (total
      number of patients = 116) most on temozolomide treatment (n = 11 studies, total
      number of patients = 106). A positive treatment effect was seen in 47% (95% CI:
      36-58%) of temozolomide treated. Data from the recently performed ESE survey on
      aggressive pituitary tumours and carcinomas (165 patients) were also used as
      backbone for the guideline. SELECTED RECOMMENDATION: (i) Patients with aggressive
      pituitary tumours should be managed by a multidisciplinary expert team. (ii)
      Histopathological analyses including pituitary hormones and proliferative markers
      are needed for correct tumour classification. (iii) Temozolomide monotherapy is
      the first-line chemotherapy for aggressive pituitary tumours and pituitary
      carcinomas after failure of standard therapies; treatment evaluation after 3
      cycles allows identification of responder and non-responder patients. (iv) In
      patients responding to first-line temozolomide, we suggest continuing treatment
      for at least 6 months in total. Furthermore, the guideline offers recommendations
      for patients who recurred after temozolomide treatment, for those who did not
      respond to temozolomide and for patients with systemic metastasis.

PMID- 29046324
TI  - ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid
      cancer of adult population.
AB  - OBJECTIVE: PTC-specific analysis identified novel fusions involving RET, BRAF,
      NTRK1, NTRK3, AGK and ALK genes in adults and pediatric PTCs. Although many novel
      fusions are PTC-specific events and, therefore, are ideal for diagnosis purposes,
      validation across additional and larger patient cohorts is essential for
      introducing these potential diagnostic or prognostic biomarkers into the clinical
      practice. As most of the BRAF, NTRK3 and ALK fusions were initially found in
      pediatric PTC or in more aggressive thyroid carcinomas, and there is a great
      disparity across population, in this study, we screened a large set of adult
      sporadic PTC cases for the most prevalent kinase fusion lately described in the
      TCGA. DESIGN AND METHODS: The prevalence of the fusions was determined by RT-PCR
      in 71 classical PTC, 45 follicular variants of PTC (FVPTC), 19 follicular thyroid
      adenomas (FTAs) and 22 follicular thyroid carcinomas (FTCs). RESULTS: ETV6-NTRK3
      was exclusively found in FVPTC, in both encapsulated and infiltrative variants,
      but was not found in FTAs and FTCs. STRN-ALK was found in both classical PTC and
      FVPTC. No AGK-BRAF fusion was identified in this series, endorsing that AGK-BRAF
      is a genetic event mainly associated with pediatric PTCs. CONCLUSIONS: The
      identification of kinase fusions in thyroid carcinomas helps to expand our
      knowledge about the landscape of oncogenic alterations in PTC. As ETV6-NTRK3 and
      STRN-ALK are recurrent and not identified in benign lesions, they can certainly
      help with diagnosis of thyroid nodules. Further analysis is needed to define if
      they can also be useful for prognosis and guiding therapy.

PMID- 29046325
TI  - Excess morbidity and mortality in patients with craniopharyngioma: a hospital
      based retrospective cohort study.
AB  - OBJECTIVE: Most studies in patients with craniopharyngioma did not investigate
      morbidity and mortality relative to the general population nor evaluated risk
      factors for excess morbidity and mortality. Therefore, the objective of this
      study was to examine excess morbidity and mortality, as well as their
      determinants in patients with craniopharyngioma. DESIGN: Hospital-based
      retrospective cohort study conducted between 1987 and 2014. METHODS: We included
      144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer
      based search in the medical records (105 females (47%), 112 patients with
      childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess
      morbidity and mortality were analysed using standardized incidence and mortality
      ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs
      and SMRs between non-overlapping subgroups. RESULTS: Patients with
      craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus
      (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8-6.8) and cerebral infarction
      (SIR: 4.9, 95% CI: 3.1-8.0) compared to the general population. Risks for
      malignant neoplasms, myocardial infarctions and fractures were not increased.
      Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95%
      CI: 2.0-3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1-4.5) and
      respiratory (SMR: 6.0, 95% CI: 2.5-14.5) diseases. Female sex, childhood-onset
      craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk
      factors for excess T2DM, cerebral infarction and total mortality. CONCLUSIONS:
      Patients with craniopharyngioma are at an increased risk for T2DM, cerebral
      infarction, total mortality and mortality due to circulatory and respiratory
      diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour
      recurrence are important risk factors.

PMID- 29046326
TI  - DIAGNOSIS OF ENDOCRINE DISEASE: Bone turnover markers: are they clinically
      useful?
AB  - Bone turnover markers (BTMs) are useful in clinical practice as they are
      inexpensive, and they have proven useful for treatment monitoring and
      identification of poor adherence. BTMs cannot be used in individual patients for
      identifying accelerated bone loss or an increase in fracture risk or in deciding
      on the optimal therapy. They are useful for monitoring both anti-resorptive and
      anabolic treatment. Response can be defined as a result that exceeds an absolute
      target, or by a change greater than the least significant change; if such a
      response is not present, then poor compliance or secondary osteoporosis are
      likely causes. A baseline BTM measurement is not always made; in that case, a
      value of BTM on anti-resorptive treatment that is low or low normal or above the
      reference interval for anabolic therapy may be taken to indicate a satisfactory
      response. We provide an approach to using these bone turnover markers in clinical
      practice by describing algorithms for anti-resorptive and anabolic therapy and
      describing the changes we observe in the clinical practice setting.

PMID- 29046327
TI  - Time Trends of Dietary and Lifestyle Factors and Their Potential Impact on
      Diabetes Burden in China.
AB  - OBJECTIVE: To examine the secular trends in risk factors, estimate their impact
      on type 2 diabetes burden from 1991 to 2011, and project trends in the next 20
      years. RESEARCH DESIGN AND METHODS: Risk factor distributions were based on data
      from the China Health and Nutrition Survey 1991-2011. Diabetes cases attributable
      to all nonoptimal levels of each risk factor were estimated by applying the
      comparative risk assessment method. RESULTS: In 2011, high BMI was the leading
      individual attributable factor for diabetes cases in China responsible for 43.8
      million diabetes cases with a population-attributable fraction of 46.8%. Low
      whole-grain intake and high refined grain intake were the leading dietary risk
      factors in China responsible for 37.8 million and 21.8 million diabetes
      attributable cases, respectively. The number of attributable diabetes cases
      associated with low physical activity, high blood pressure, and current smoking
      was 29.5, 21.6, and 9.8 million, respectively. Although intakes of low-fat dairy
      products, nuts, fruit, vegetables, and fish and seafood increased moderately over
      time, the average intake was below optimal levels in 2011 and were responsible
      for 15.8, 11.3, 9.9, 6.0, 3.6, and 2.6 million diabetes cases, respectively.
      Meanwhile, intakes of processed meat, red meat, and sugar-sweetened beverage
      showed increasing trends over time and were responsible for 2.8, 1.8, and 0.5
      million diabetes cases, respectively, in 2011. CONCLUSIONS: A high BMI and low
      intake of whole grains but high intake of refined grains are the most important
      individual risk factors related to Chinese diabetes burden; low physical activity
      and high blood pressure also significantly contributed.

PMID- 29046329
TI  - Copy Number Variations in Serum Amyloid A Play a Role in the Determination of its
      Individual Baseline Concentrations.

PMID- 29046328
TI  - Genetic Support for a Causal Role of Insulin Resistance on Circulating Branched
      Chain Amino Acids and Inflammation.
AB  - OBJECTIVE: Insulin resistance has deleterious effects on cardiometabolic disease.
      We used Mendelian randomization analyses to clarify the causal relationships of
      insulin resistance (IR) on circulating blood-based metabolites to shed light on
      potential mediators of the IR to cardiometabolic disease relationship. RESEARCH
      DESIGN AND METHODS: We used 53 single nucleotide polymorphisms associated with IR
      from a recent genome-wide association study (GWAS) to explore their effects on
      circulating lipids and metabolites. We used published summary-level data from two
      GWASs of European individuals; data on the exposure (IR) were obtained from meta
      GWASs of 188,577 individuals, and data on the outcomes (58 metabolic measures
      assessed by nuclear magnetic resonance) were taken from a GWAS of 24,925
      individuals. RESULTS: One-SD genetically elevated IR (equivalent to 55% higher
      geometric mean of fasting insulin, 0.89 mmol/L higher triglycerides, and 0.46
      mmol/L lower HDL cholesterol) was associated with higher concentrations of all
      branched-chain amino acids (BCAAs)-isoleucine (0.56 SD; 95% CI 0.43, 0.70),
      leucine (0.42 SD; 95% CI 0.28, 0.55), and valine (0.26 SD; 95% CI 0.12, 0.39)-as
      well as with higher glycoprotein acetyls (an inflammation marker) (0.47 SD; 95%
      CI 0.32, 0.62) (P < 0.0003 for each). Results were broadly consistent when using
      multiple sensitivity analyses to account for potential genetic pleiotropy.
      CONCLUSIONS: We provide robust evidence that IR causally affects each individual
      BCAA and inflammation. Taken together with existing studies, this implies that
      BCAA metabolism lies on a causal pathway from adiposity and IR to type 2
      diabetes.

PMID- 29046330
TI  - Systematic Review and Metaanalysis Comparing the Bias and Accuracy of the
      Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology
      Collaboration Equations in Community-Based Populations.
AB  - BACKGROUND: The majority of patients with chronic kidney disease are diagnosed
      and monitored in primary care. Glomerular filtration rate (GFR) is a key marker
      of renal function, but direct measurement is invasive; in routine practice,
      equations are used for estimated GFR (eGFR) from serum creatinine. We
      systematically assessed bias and accuracy of commonly used eGFR equations in
      populations relevant to primary care. CONTENT: MEDLINE, EMBASE, and the Cochrane
      Library were searched for studies comparing measured GFR (mGFR) with eGFR in
      adult populations comparable to primary care and reporting both the Modification
      of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equations based on standardized creatinine measurements.
      We pooled data on mean bias (difference between eGFR and mGFR) and on mean
      accuracy (proportion of eGFR within 30% of mGFR) using a random-effects inverse
      variance weighted metaanalysis. We included 48 studies of 26875 patients that
      reported data on bias and/or accuracy. Metaanalysis of within-study comparisons
      in which both formulae were tested on the same patient cohorts using isotope
      dilution-mass spectrometry-traceable creatinine showed a lower mean bias in eGFR
      using CKD-EPI of 2.2 mL/min/1.73 m2 (95% CI, 1.1-3.2; 30 studies; I2 = 74.4%) and
      a higher mean accuracy of CKD-EPI of 2.7% (1.6-3.8; 47 studies; I2 = 55.5%).
      Metaregression showed that in both equations bias and accuracy favored the CKD
      EPI equation at higher mGFR values. SUMMARY: Both equations underestimated mGFR,
      but CKD-EPI gave more accurate estimates of GFR.

PMID- 29046331
TI  - Comprehensive Age and Sex 99th Percentiles for a High-Sensitivity Cardiac
      Troponin I Assay.

PMID- 29046332
TI  - Adipose Tissue LPL Methylation is Associated with Triglyceride Concentrations in
      the Metabolic Syndrome.
AB  - BACKGROUND: DNA methylation is one of the epigenetic mechanisms that regulate
      gene expression. DNA methylation may be modified by environmental and nutritional
      factors. Thus, epigenetics could potentially provide a mechanism to explain the
      etiology of metabolic disorders, such as metabolic syndrome (MetS). The aim of
      this study was to analyze the level of DNA methylation of several lipoprotein
      lipase (LPL)-promoter-CpG dinucleotides in a CpG island region and relate this to
      the gene and protein expression levels in human visceral adipose tissue (VAT)
      from individuals with and without MetS. METHODS: VAT samples were collected from
      laparoscopic surgical patients without and with MetS, and levels of LPL mRNA, LPL
      protein, and LPL DNA methylation were measured by qPCR, western blot, and
      pyrosequencing. Biochemical and anthropometric variables were analyzed.
      Individuals included in a subset underwent a dietary fat challenge test, and
      levels of postprandial triglycerides were determined. RESULTS: We found higher
      levels of DNA methylation in MetS patients but lower gene expression and protein
      levels. There was a negative association between LPL methylation and LPL gene
      expression. We found a positive association between LPL methylation status and
      abnormalities of the metabolic profile and basal and postprandial triglycerides,
      whereas LPL gene expression was negatively associated with these abnormalities.
      CONCLUSIONS: We demonstrate that LPL methylation may be influenced by the degree
      of metabolic disturbances and could be involved in triglyceride metabolism,
      promoting hypertriglyceridemia and subsequent associated disorders, such as MetS.

PMID- 29046333
TI  - The p53-inducible long noncoding RNA TRINGS protects cancer cells from necrosis
      under glucose starvation.
AB  - The tumor suppressor p53 is activated in response to cellular stress to prevent
      malignant transformation. However, several recent studies have shown that p53 can
      play protective roles in tumor cell survival under adversity. Whether p53
      regulated long noncoding RNAs are involved in this process remains to be fully
      understood. Here, we show that under glucose starvation condition, p53 directly
      upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis
      under glucose starvation) in human tumor cells. TRINGS binds to STRAP and
      inhibits STRAP-GSK3beta-NF-kappaB necrotic signaling to protect tumor cells from
      cell death. Interestingly, TRINGS appears to respond to glucose starvation
      specifically, as it is not activated by serum, serine, or glutamine deprivation.
      Collectively, our findings reveal that p53-induced lncRNA TRINGS controls the
      necrotic pathway and contributes to the survival of cancer cells harboring wild
      type p53 under glucose stress.

PMID- 29046334
TI  - The organic anion transporter SLCO2A1 constitutes the core component of the Maxi
      Cl channel.
AB  - The maxi-anion channels (MACs) are expressed in cells from mammals to amphibians
      with ~60% exhibiting a phenotype called Maxi-Cl. Maxi-Cl serves as the most
      efficient pathway for regulated fluxes of inorganic and organic anions including
      ATP However, its molecular entity has long been elusive. By subjecting proteins
      isolated from bleb membranes rich in Maxi-Cl activity to LC-MS/MS combined with
      targeted siRNA screening, CRISPR/Cas9-mediated knockout, and heterologous
      overexpression, we identified the organic anion transporter SLCO2A1, known as a
      prostaglandin transporter (PGT), as a key component of Maxi-Cl. Recombinant
      SLCO2A1 exhibited Maxi-Cl activity in reconstituted proteoliposomes. When
      SLCO2A1, but not its two disease-causing mutants, was heterologously expressed in
      cells which lack endogenous SLCO2A1 expression and Maxi-Cl activity, Maxi-Cl
      currents became activated. The charge-neutralized mutant became weakly cation
      selective with exhibiting a smaller single-channel conductance. Slco2a1 silencing
      in vitro and in vivo, respectively, suppressed the release of ATP from swollen
      C127 cells and from Langendorff-perfused mouse hearts subjected to ischemia
      reperfusion. These findings indicate that SLCO2A1 is an essential core component
      of the ATP-conductive Maxi-Cl channel.

PMID- 29046336
TI  - PP2A Inactivation Mediated by PPP2R4 Haploinsufficiency Promotes Cancer
      Development.
AB  - Protein phosphatase 2A (PP2A) complexes counteract many oncogenic kinase
      pathways. In cancer cells, PP2A function can be compromised by several
      mechanisms, including sporadic mutations in its scaffolding A and regulatory B
      subunits or more frequently through overexpression of cellular PP2A inhibitors.
      Here, we identify a novel genetic mechanism by which PP2A function is recurrently
      affected in human cancer, involving haploinsufficiency of PPP2R4, a gene encoding
      the cellular PP2A activator PTPA. Notably, up to 70% of cancer patients showed a
      heterozygous deletion or missense mutations in PPP2R4 Cancer-associated PTPA
      mutants exhibited decreased abilities to bind the PP2A-C subunit or activate PP2A
      and failed to reverse the tumorigenic phenotype induced by PTPA suppression,
      indicating they function as null alleles. In Ppp2r4 gene-trapped (gt) mice
      showing residual PTPA expression, total PP2A activity and methylation were
      reduced, selectively affecting specific PP2A holoenzymes. Both PTPAgt/gt and
      PTPA+/gt mice showed higher rates of spontaneous tumors, mainly hematologic
      malignancies and hepatocellular adenomas and carcinomas. These tumors exhibited
      increased c-Myc phosphorylation and increased Wnt or Hedgehog signaling. We
      observed a significant reduction in lifespan in PTPA+/gt mice compared with wild
      type mice. In addition, chemical-induced skin carcinogenesis was accelerated in
      PTPA+/gt compared with wild-type mice. Our results provide evidence for PPP2R4 as
      a haploinsufficient tumor suppressor gene, defining a high-penetrance genetic
      mechanism for PP2A inhibition in human cancer. Cancer Res; 77(24); 6825-37.
      (c)2017 AACR.

PMID- 29046335
TI  - Molecular basis for inner kinetochore configuration through RWD domain-peptide
      interactions.
AB  - Kinetochores are dynamic cellular structures that connect chromosomes to
      microtubules. They form from multi-protein assemblies that are evolutionarily
      conserved between yeasts and humans. One of these assemblies-COMA-consists of
      subunits Ame1CENP-U, Ctf19CENP-P, Mcm21CENP-O and Okp1CENP-Q A description of
      COMA molecular organization has so far been missing. We defined the subunit
      topology of COMA, bound with inner kinetochore proteins Nkp1 and Nkp2, from the
      yeast Kluyveromyces lactis, with nanoflow electrospray ionization mass
      spectrometry, and mapped intermolecular contacts with hydrogen-deuterium exchange
      coupled to mass spectrometry. Our data suggest that the essential Okp1 subunit is
      a multi-segmented nexus with distinct binding sites for Ame1, Nkp1-Nkp2 and Ctf19
      Mcm21. Our crystal structure of the Ctf19-Mcm21 RWD domains bound with Okp1 shows
      the molecular contacts of this important inner kinetochore joint. The Ctf19-Mcm21
      binding motif in Okp1 configures a branch of mitotic inner kinetochores, by
      tethering Ctf19-Mcm21 and Chl4CENP-N-Iml3CENP-L Absence of this motif results in
      dependence on the mitotic checkpoint for viability.

PMID- 29046337
TI  - Cathepsin B Is Dispensable for Cellular Processing of Cathepsin B-Cleavable
      Antibody-Drug Conjugates.
AB  - Antibody-drug conjugates (ADC) are designed to selectively bind to tumor antigens
      via the antibody and release their cytotoxic payload upon internalization.
      Controllable payload release through judicious design of the linker has been an
      early technological milestone. Here, we examine the effect of the protease
      cleavable valine-citrulline [VC(S)] linker on ADC efficacy. The VC(S) linker was
      designed to be cleaved by cathepsin B, a lysosomal cysteine protease.
      Surprisingly, suppression of cathepsin B expression via CRISPR-Cas9 gene deletion
      or shRNA knockdown had no effect on the efficacy of ADCs with VC(S) linkers armed
      with a monomethyl auristatin E (MMAE) payload. Mass spectrometry studies of
      payload release suggested that other cysteine cathepsins can cleave the VC(S)
      linker. Also, ADCs with a nonprotease-cleavable enantiomer, the VC(R) isomer,
      mediated effective cell killing with a cysteine-VC(R)-MMAE catabolite generated
      by lysosomal catabolism. Based on these observations, we altered the payload to a
      pyrrolo[2,1-c][1,4]benzodiazepine dimer (PBD) conjugate that requires linker
      cleavage in order to bind its DNA target. Unlike the VC-MMAE ADCs, the VC(S)-PBD
      ADC is at least 20-fold more cytotoxic than the VC(R)-PBD ADC. Our findings
      reveal that the VC(S) linker has multiple paths to produce active catabolites and
      that antibody and intracellular targets are more critical to ADC efficacy. These
      results suggest that protease-cleavable linkers are unlikely to increase the
      therapeutic index of ADCs and that resistance based on linker processing is
      improbable. Cancer Res; 77(24); 7027-37. (c)2017 AACR.

PMID- 29046339
TI  - A checkpoint-independent mechanism delays entry into mitosis after UV
      irradiation.
AB  - When cells are exposed to stress they delay entry into mitosis. The most
      extensively studied mechanism behind this delay is the DNA-damage-induced G2/M
      checkpoint. Here, we show the existence of an additional stress-response pathway
      in Schizosaccharomyces pombe that is independent of the classic ATR/Rad3
      dependent checkpoint. This novel mechanism delays entry mitosis independently of
      the spindle assembly checkpoint and the mitotic kinases Fin1, Ark1 and Plo1. The
      pathway delays activation of the mitotic cyclin-dependent kinase (CDK) Cdc2 after
      UV irradiation. Furthermore, we demonstrate that translation of the mitotic
      cyclin Cdc13 is selectively downregulated after UV irradiation, and we propose
      that this downregulation of Cdc13 contributes to the delayed activation of Cdc2
      and the delayed mitosis.

PMID- 29046338
TI  - Regulation of valve interstitial cell homeostasis by mechanical deformation:
      implications for heart valve disease and surgical repair.
AB  - Mechanical stress is one of the major aetiological factors underlying soft-tissue
      remodelling, especially for the mitral valve (MV). It has been hypothesized that
      altered MV tissue stress states lead to deviations from cellular homeostasis,
      resulting in subsequent cellular activation and extracellular matrix (ECM)
      remodelling. However, a quantitative link between alterations in the organ-level
      in vivo state and in vitro-based mechanobiology studies has yet to be made. We
      thus developed an integrated experimental-computational approach to elucidate MV
      tissue and interstitial cell responses to varying tissue strain levels.
      Comprehensive results at different length scales revealed that normal responses
      are observed only within a defined range of tissue deformations, whereas
      deformations outside of this range lead to hypo- and hyper-synthetic responses,
      evidenced by changes in alpha-smooth muscle actin, type I collagen, and other ECM
      and cell adhesion molecule regulation. We identified MV interstitial cell
      deformation as a key player in leaflet tissue homeostatic regulation and, as
      such, used it as the metric that makes the critical link between in vitro
      responses to simulated equivalent in vivo behaviour. Results indicated that cell
      responses have a delimited range of in vivo deformations that maintain a
      homeostatic response, suggesting that deviations from this range may lead to
      deleterious tissue remodelling and failure.

PMID- 29046340
TI  - NNT is a key regulator of adrenal redox homeostasis and steroidogenesis in male
      mice.
AB  - Nicotinamide nucleotide transhydrogenase, NNT, is a ubiquitous protein of the
      inner mitochondrial membrane with a key role in mitochondrial redox balance. NNT
      produces high concentrations of NADPH for detoxification of reactive oxygen
      species by glutathione and thioredoxin pathways. In humans, NNT dysfunction leads
      to an adrenal-specific disorder, glucocorticoid deficiency. Certain substrains of
      C57BL/6 mice contain a spontaneously occurring inactivating Nnt mutation and
      display glucocorticoid deficiency along with glucose intolerance and reduced
      insulin secretion. To understand the underlying mechanism(s) behind the
      glucocorticoid deficiency, we performed comprehensive RNA-seq on adrenals from
      wild-type (C57BL/6N), mutant (C57BL/6J) and BAC transgenic mice overexpressing
      Nnt (C57BL/6JBAC). The following results were obtained. Our data suggest that Nnt
      deletion (or overexpression) reduces adrenal steroidogenic output by decreasing
      the expression of crucial, mitochondrial antioxidant (Prdx3 and Txnrd2) and
      steroidogenic (Cyp11a1) enzymes. Pathway analysis also revealed upregulation of
      heat shock protein machinery and haemoglobins possibly in response to the
      oxidative stress initiated by NNT ablation. In conclusion, using transcriptomic
      profiling in adrenals from three mouse models, we showed that disturbances in
      adrenal redox homeostasis are mediated not only by under expression of NNT but
      also by its overexpression. Further, we demonstrated that both under expression
      or overexpression of NNT reduced corticosterone output implying a central role
      for it in the control of steroidogenesis. This is likely due to a reduction in
      the expression of a key steroidogenic enzyme, Cyp11a1, which mirrored the
      reduction in corticosterone output.

PMID- 29046341
TI  - Influence of the membrane environment on cholesterol transfer.
AB  - Cholesterol, an essential component in biological membranes, is highly unevenly
      distributed within the cell, with most localized in the plasma membrane while
      only a small fraction is found in the endoplasmic reticulum, where it is
      synthesized. Cellular membranes differ in lipid composition and protein content,
      and these differences can exist across their leaflets too. This thermodynamic
      landscape that cellular membranes impose on cholesterol is expected to modulate
      its transport. To uncover the role the membrane environment has on cholesterol
      inter- and intra-membrane movement, we used time-resolved small angle neutron
      scattering to study the passive movement of cholesterol between and within
      membranes with varying degrees of saturation content. We found that cholesterol
      moves systematically slower as the degree of saturation in the membranes
      increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is
      unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully
      saturated. Additionally, we found that the energetic barrier to move cholesterol
      in these phosphatidylcholine membranes is independent of their relative lipid
      composition and remains constant for both flip-flop and exchange at ~100 kJ/mol.
      Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an
      abundant saturated lipid of the outer leaflet of the plasma membrane, we found
      the rates decreased by a factor of two. This finding is in stark contrast with
      recent molecular dynamic simulations that predict a dramatic slow-down of seven
      orders of magnitude for cholesterol flipping in membranes with a similar
      phosphocholine and SM lipid composition.

PMID- 29046342
TI  - The pioneering of intracytoplasmic sperm injection: historical perspectives.
AB  - Intracytoplasmic sperm injection (ICSI) has often been heralded as a ground
      breaking technique that has transformed the treatment of couples with
      infertility. By injecting a single spermatozoon into the cytoplasm of the oocyte,
      ICSI bypasses the zona pellucida and increases the chances of fertilization and
      subsequent embryo development, independent of semen parameters. Ever since the
      first live births using ICSI were reported in 1992, ICSI has become the mainstay
      of treating male factor infertility as well as overcoming fertilization failure
      associated with conventional in vitro insemination. Today, ICSI is utilized in
      nearly 66% of all assisted reproductive treatments worldwide and has resulted in
      the birth of millions of babies. The primary goal of this review is to provide
      historical perspectives about the pioneering of ICSI. We begin by highlighting
      the scientific work of early investigators who elucidated the mechanisms central
      to mammalian fertilization. Furthermore, we briefly discuss how these findings
      contributed to the development of IVF for the treatment of infertility. We then
      emphasize the shortcomings of IVF in treating severe forms of male factor
      infertility and enumerate the micromanipulation techniques that were developed to
      circumvent these shortcomings. Finally, we indicate how the inadequacies of these
      micromanipulation techniques lead to the inception, application and popularity of
      ICSI.

PMID- 29046344
TI  - Kinetochore-microtubule interactions in chromosome segregation: lessons from
      yeast and mammalian cells.
AB  - Chromosome congression and segregation require robust yet dynamic attachment of
      the kinetochore with the spindle microtubules. Force generated at the kinetochore
      microtubule interface plays a vital role to drive the attachment, as it is
      required to move chromosomes and to provide signal to sense correct attachments.
      To understand the mechanisms underlying these processes, it is critical to
      describe how the force is generated and how the molecules at the kinetochore
      microtubule interface are organized and assembled to withstand the force and
      respond to it. Research in the past few years or so has revealed interesting
      insights into the structural organization and architecture of kinetochore
      proteins that couple kinetochore attachment to the spindle microtubules.
      Interestingly, despite diversities in the molecular players and their modes of
      action, there appears to be architectural similarity of the kinetochore-coupling
      machines in lower to higher eukaryotes. The present review focuses on the most
      recent advances in understanding of the molecular and structural aspects of
      kinetochore-microtubule interaction based on the studies in yeast and vertebrate
      cells.

PMID- 29046343
TI  - Complement Activation in Peritoneal Dialysis-Induced Arteriolopathy.
AB  - Cardiovascular disease (CVD) is the leading cause of increased mortality in
      patients with CKD and is further aggravated by peritoneal dialysis (PD). Children
      are devoid of preexisting CVD and provide unique insight into specific uremia-
      and PD-induced pathomechanisms of CVD. We obtained peritoneal specimens from
      children with stage 5 CKD at time of PD catheter insertion (CKD5 group), children
      with established PD (PD group), and age-matched nonuremic controls (n=6/group).
      We microdissected omental arterioles from tissue layers not directly exposed to
      PD fluid and used adjacent sections of four arterioles per patient for
      transcriptomic and proteomic analyses. Findings were validated in omental and
      parietal arterioles from independent pediatric control (n=5), CKD5 (n=15), and PD
      (n=15) cohorts. Transcriptomic analysis revealed differential gene expression in
      control versus CKD5 arterioles and in CKD5 versus PD arterioles. Gene ontology
      analyses revealed activation of metabolic processes in CKD5 arterioles and of
      inflammatory, immunologic, and stress-response cascades in PD arterioles. PD
      arterioles exhibited particular upregulation of the complement system and
      respective regulatory pathways, with concordant findings at the proteomic level.
      In the validation cohorts, PD specimens had the highest abundance of omental and
      parietal arteriolar C1q, C3d, terminal complement complex, and phosphorylated
      SMAD2/3, a downstream effector of TGF-beta Furthermore, in the PD parietal
      arterioles, C1q and terminal complement complex abundance correlated with the
      level of dialytic glucose exposure, abundance of phosphorylated SMAD2/3, and
      degree of vasculopathy. We conclude that PD fluids activate arteriolar complement
      and TGF-beta signaling, which quantitatively correlate with the severity of
      arteriolar vasculopathy.

PMID- 29046345
TI  - Endoplasmic Reticulum Transmembrane Proteins ZDHHC1 and STING Both Act as Direct
      Adaptors for IRF3 Activation in Teleost.
AB  - IFN regulatory factor (IRF)3 is a central regulator for IFN-beta expression in
      different types of pathogenic infections. Mammals have various pathogenic sensors
      that are involved in monitoring pathogen intrusions. These sensors can trigger
      IRF3-mediated antiviral responses through different pathways. Endoplasmic
      reticulum-associated proteins stimulator of IFN gene (STING) and zinc finger DHHC
      type containing 1 (ZDHHC1) are critical mediators of IRF3 activation in response
      to viral DNA infections. In this study, grass carp STING and ZDHHC1 were found to
      have some similar molecular features and subcellular localization, and both were
      upregulated upon stimulation with polyinosinic:polycytidylic acid, B-DNA, or Z
      DNA. Based on these results, we suggest that grass carp STING and ZDHHC1 might
      possess some properties similar to their mammalian counterparts. Overexpression
      of ZDHHC1 and STING in Ctenopharyngodon idella kidney cells upregulated IFN
      expression, whereas knockdown of IRF3 inhibited IFN activation. In addition,
      coimmunoprecipitation and GST pull-down assays demonstrated that STING and ZDHHC1
      can interact separately with IRF3 and promote the dimerization and nuclear
      translocation of IRF3. Furthermore, we also found that small interfering RNA
      mediated knockdown of STING could inhibit the expression of IFN and ZDHHC1 in
      fish cells. Similarly, knockdown of STING resulted in inhibition of the IFN
      promoter. In contrast, ZDHHC1 knockdown also inhibited IFN expression but had no
      apparent effect on STING, which indicates that STING is necessary for IFN
      activation through ZDHHC1. In conclusion, STING and ZDHHC1 in fish can respond to
      viral DNA or RNA molecules in cytoplasm, as well as activate IRF3 and,
      eventually, trigger IFN expression.

PMID- 29046347
TI  - Investigating Immune Gene Signatures in Peripheral Blood from Subjects with
      Allergic Rhinitis Undergoing Nasal Allergen Challenge.
AB  - Nasal allergen challenge (NAC) is a human model of allergic rhinitis (AR) that
      delivers standardized allergens locally to the nasal mucosa allowing clinical
      symptoms and biospecimens such as peripheral blood to be collected. Although many
      studies have focused on local inflammatory sites, peripheral blood, an important
      mediator and a component of the systemic immune response, has not been well
      studied in the setting of AR. We sought to investigate immune gene signatures in
      peripheral blood collected after NAC under the setting of AR. Clinical symptoms
      and peripheral blood samples from AR subjects were collected during NAC. Fuzzy c
      means clustering method was used to identify immune gene expression patterns in
      blood over time points (before NAC and 1, 2, and 6 h after NAC). We identified
      and validated seven clusters of differentially expressed immune genes after NAC
      onset. Clusters 2, 3, and 4 were associated with neutrophil and lymphocyte
      frequencies and neutrophil/lymphocyte ratio after the allergen challenge. The
      patterns of the clusters and immune cell frequencies were associated with the
      clinical symptoms of the AR subjects and were significantly different from
      healthy nonallergic subjects who had also undergone NAC. Our approach identified
      dynamic signatures of immune gene expression in blood as a systemic immune
      response associated with clinical symptoms after NAC. The immune gene signatures
      may allow cross-sectional investigation of the pathophysiology of AR and may also
      be useful as a potential objective measurement for diagnosis and treatment of AR
      combined with the NAC model.

PMID- 29046346
TI  - T Cell-Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell
      Responses.
AB  - The CD27-CD70 pathway is known to provide a costimulatory signal, with CD70
      expressed on APCs and CD27 functions on T cells. Although CD70 is also expressed
      on activated T cells, it remains unclear how T cell-derived CD70 affects T cell
      function. Therefore, we have assessed the role of T cell-derived CD70 using
      adoptive-transfer models, including autoimmune inflammatory bowel disease and
      allogeneic graft-versus-host disease. Surprisingly, compared with wild-type T
      cells, CD70-/- T cells caused more severe inflammatory bowel disease and graft
      versus-host disease and produced higher levels of inflammatory cytokines.
      Mechanistic analyses reveal that IFN-gamma induces CD70 expression in T cells,
      and CD70 limits T cell expansion via a regulatory T cell-independent mechanism
      that involves caspase-dependent T cell apoptosis and upregulation of inhibitory
      immune checkpoint molecules. Notably, T cell-intrinsic CD70 signaling
      contributes, as least in part, to the inhibitory checkpoint function. Overall,
      our findings demonstrate for the first time, to our knowledge, that T cell
      derived CD70 plays a novel immune checkpoint role in inhibiting inflammatory T
      cell responses. This study suggests that T cell-derived CD70 performs a critical
      negative feedback function to downregulate inflammatory T cell responses.

PMID- 29046348
TI  - D1-Asn-298 in photosystem II is involved in a hydrogen-bond network near the
      redox-active tyrosine YZ for proton exit during water oxidation.
AB  - In photosynthetic water oxidation, two water molecules are converted into one
      oxygen molecule and four protons at the Mn4CaO5 cluster in photosystem II (PSII)
      via the S-state cycle. Efficient proton exit from the catalytic site to the lumen
      is essential for this process. However, the exit pathways of individual protons
      through the PSII proteins remain to be identified. In this study, we examined the
      involvement of a hydrogen-bond network near the redox-active tyrosine YZ in
      proton transfer during the S-state cycle. We focused on spectroscopic analyses of
      a site-directed variant of D1-Asn-298, a residue involved in a hydrogen-bond
      network near YZ We found that the D1-N298A mutant of Synechocystis sp. PCC 6803
      exhibits an O2 evolution activity of ~10% of the wild-type. D1-N298A and the wild
      type D1 had very similar features of thermoluminescence glow curves and of an
      FTIR difference spectrum upon YZ oxidation, suggesting that the hydrogen-bonded
      structure of YZ and electron transfer from the Mn4CaO5 cluster to YZ were little
      affected by substitution. In the D1-N298A mutant, however, the flash-number
      dependence of delayed luminescence showed a monotonic increase without
      oscillation, and FTIR difference spectra of the S-state cycle indicated partial
      and significant inhibition of the S2 -> S3 and S3 -> S0 transitions,
      respectively. These results suggest that the D1-N298A substitution inhibits the
      proton transfer processes in the S2 -> S3 and S3 -> S0 transitions. This in turn
      indicates that the hydrogen-bond network near YZ can be functional as a proton
      transfer pathway during photosynthetic water oxidation.

PMID- 29046349
TI  - Differential regulation of the Rac1 GTPase-activating protein (GAP) BCR during
      oxygen/glucose deprivation in hippocampal and cortical neurons.
AB  - Brain ischemia causes oxygen and glucose deprivation (OGD) in neurons, triggering
      a cascade of events leading to synaptic accumulation of glutamate. Excessive
      activation of glutamate receptors causes excitotoxicity and delayed cell death in
      vulnerable neurons. Following global cerebral ischemia, hippocampal CA1 pyramidal
      neurons are more vulnerable to injury than their cortical counterparts, but the
      mechanisms that underlie this difference are unclear. Signaling via Rho-family
      small GTPases, their upstream guanine nucleotide exchange factors, and GTPase
      activating proteins (GAPs) is differentially dysregulated in response to
      OGD/ischemia in hippocampal and cortical neurons. Increased Rac1 activity caused
      by OGD/ischemia contributes to neuronal death in hippocampal neurons via diverse
      effects on NADPH oxidase activity and dendritic spine morphology. The Rac1
      guanine nucleotide exchange factor Tiam1 mediates an OGD-induced increase in Rac1
      activity in hippocampal neurons; however, the identity of an antagonistic GAP
      remains elusive. Here we show that the Rac1 GAP breakpoint cluster region (BCR)
      associates with NMDA receptors (NMDARs) along with Tiam1 and that this protein
      complex is more abundant in hippocampal compared with cortical neurons. Although
      total BCR is similar in the two neuronal types, BCR is more active in hippocampal
      compared with cortical neurons. OGD causes an NMDAR- and Ca2+-permeable AMPAR
      dependent deactivation of BCR in hippocampal but not cortical neurons. BCR
      knockdown occludes OGD-induced Rac1 activation in hippocampal neurons.
      Furthermore, disrupting the Tiam1-NMDAR interaction with a fragment of Tiam1
      blocks OGD-induced Tiam1 activation but has no effect on the deactivation of BCR.
      This work identifies BCR as a critical player in Rac1 regulation during OGD in
      hippocampal neurons.

PMID- 29046350
TI  - Host transcription factor Speckled 110 kDa (Sp110), a nuclear body protein, is
      hijacked by hepatitis B virus protein X for viral persistence.
AB  - Promyelocytic leukemia nuclear bodies (PML-NB) are sub-nuclear organelles that
      are the hub of numerous proteins. DNA/RNA viruses often hijack the cellular
      factors resident in PML-NBs to promote their proliferation in host cells.
      Hepatitis B virus (HBV), belonging to Hepadnaviridae family, remains undetected
      in early infection as it does not induce the innate immune response and is known
      to be the cause of several hepatic diseases leading to cirrhosis and
      hepatocellular carcinoma. The association of PML-NB proteins and HBV is being
      addressed in a number of recent studies. Here, we report that the PML-NB protein
      Speckled 110 kDa (Sp110) is SUMO1-modified and undergoes a deSUMOylation-driven
      release from the PML-NB in the presence of HBV. Intriguingly, Sp110 knockdown
      significantly reduced viral DNA load in the culture supernatant by activation of
      the type I interferon-response pathway. Furthermore, we found that Sp110
      differentially regulates several direct target genes of hepatitis B virus protein
      X (HBx), a viral co-factor. Subsequently, we identified Sp110 as a novel
      interactor of HBx and found this association to be essential for the exit of
      Sp110 from the PML-NB during HBV infection and HBx recruitment on the promoter of
      these genes. HBx, in turn, modulates the recruitment of its associated
      transcription cofactors p300/HDAC1 to these co-regulated genes, thereby altering
      the host gene expression program in favor of viral persistence. Thus, we report a
      mechanism by which HBV can evade host immune response by hijacking the PML-NB
      protein Sp110, and therefore, we propose it to be a novel target for antiviral
      therapy.

PMID- 29046352
TI  - The lignan manassantin is a potent and specific inhibitor of mitochondrial
      complex I and bioenergetic activity in mammals.
AB  - Dineolignans manassantin A and B from the plant Saururus cernuus are used in
      traditional medicine to manage a wide range of ailments such as edema, jaundice,
      and gonorrhea. Cell-based studies have identified several molecular target
      candidates of manassantin including NF-kappaB, MAPK, STAT3, and hypoxia-inducible
      factor 1alpha (HIF-1alpha). It is unclear whether or how these structurally
      diverse proteins or pathways mediate any of the medical benefits of manassantin
      in vivo Moreover, it has recently been reported that manassantin causes
      developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but
      it is unknown whether manassantin inhibits mitochondrial respiration in intact
      mammalian cells and live animals. Here, we present direct evidence that
      manassantin potently and specifically inhibits the mitochondrial complex I and
      bioenergetic activity in mammalian systems. Manassantin had no effect on complex
      II- or complex IV-mediated respiration. Of note, it decreased NADH-ubiquinone
      reductase activity but not the activity of NADH-ferricyanide reductase. Treatment
      with manassantin reduced cellular ATP levels and concomitantly stimulated AMP
      activated protein kinase in vitro and in vivo As an adaptive response to
      manassantin-induced bioenergetic deficiency, mammalian cells up-regulated aerobic
      glycolysis, a process mediated by AMP-activated protein kinase (AMPK)
      independently of HIF-1alpha. Together these results demonstrate a biologically
      important activity of manassantin in the control of complex I-mediated
      respiration and its profound effects on oxygen utilization, energy homeostasis,
      and glucose metabolism in mammalian cells.

PMID- 29046351
TI  - An improved labeling strategy enables automated detection of single-virus fusion
      and assessment of HIV-1 protease activity in single virions.
AB  - Enveloped viruses transfer their genomes into host cells by fusing their membrane
      to that of the cell. To visualize single-virus fusion in living cells,
      researchers take advantage of the proteolytic maturation of HIV, type 1 (HIV-1),
      which can generate free fluorescent proteins within the viral particle. Co
      labeling viruses with a content marker and a fluorescently tagged Vpr (a viral
      core protein) enables detection of single-virus fusions, but a major limitation
      of this approach is that not all viral particles incorporate both markers. Here
      we designed a labeling strategy based on the bifunctional mCherry-2xCL-YFP-Vpr
      construct, in which 2xCL denotes a tandem cleavage site for the viral protease.
      This bifunctional marker was efficiently cleaved during virus maturation,
      producing free mCherry and the core-associated YFP-Vpr. A nearly perfect
      colocalization of these two markers in virions and their fixed 1:1 ratio enabled
      automated detection of single-particle fusion in both fixed and live cells based
      on loss of the mCherry signal. Furthermore, a drop in FRET efficiency between YFP
      and mCherry because of cleavage of the bifunctional marker, which manifested as a
      marked shift in the normalized YFP/mCherry fluorescence ratio, reliably predicted
      viral protease activity in single virions. This feature could discriminate
      between the particles containing free mCherry, and therefore likely representing
      mature viruses, and immature particles whose fusion cannot be detected. In
      summary, our new labeling strategy offers several advantages compared with
      previous approaches, including increased reliability and throughput of detection
      of viral fusion. We anticipate that our method will have significant utility for
      studying viral fusion and maturation.

PMID- 29046353
TI  - A mechanistic model to predict effects of cathepsin B and cystatin C on beta
      amyloid aggregation and degradation.
AB  - beta-Amyloid (Abeta) aggregation is thought to initiate a cascade of
      neurodegenerative events in Alzheimer's disease (AD). Much effort is underway to
      develop strategies to reduce Abeta concentration or inhibit aggregation.
      Cathepsin B (CatB) proteolytically degrades Abeta into non-aggregating fragments
      but is potently inhibited by cystatin C (CysC). It has been suggested that
      decreasing CysC would facilitate Abeta clearance by relieving CatB inhibition.
      However, CysC binds Abeta and inhibits Abeta aggregation, suggesting that an
      intervention that increases CysC would prevent Abeta aggregation. Both approaches
      have been tested in animal models, yielding contradictory results, possibly
      because of the opposing influences of CysC on Abeta degradation versus
      aggregation. Here, we sought to develop a model that quantitatively predicts the
      effects of CysC and CatB on Abeta aggregation. Abeta aggregation kinetics in the
      absence of CatB or CysC was measured. The rate constant for Abeta degradation by
      CatB and the equilibrium constant for binding of CysC to Abeta were determined.
      We derived a mathematical model that combines material balances and kinetic rate
      equations. The model accurately predicted Abeta aggregation kinetics at various
      CatB and CysC concentrations. We derived approximate expressions for the half
      times of degradation and aggregation and show that their ratio can be used to
      estimate, at any given Abeta, CatB, or CysC concentration, whether Abeta
      aggregation or degradation will result. Our results may be useful for designing
      experiments and interpreting results from investigations of manipulation of CysC
      concentration as an AD therapy.

PMID- 29046354
TI  - Evidence for a conserved inhibitory binding mode between the membrane fusion
      assembly factors Munc18 and syntaxin in animals.
AB  - The membrane fusion necessary for vesicle trafficking is driven by the assembly
      of heterologous SNARE proteins orchestrated by the binding of Sec1/Munc18 (SM)
      proteins to specific syntaxin SNARE proteins. However, the precise mode of
      interaction between SM proteins and SNAREs is debated, as contrasting binding
      modes have been found for different members of the SM protein family, including
      the three vertebrate Munc18 isoforms. While different binding modes could be
      necessary, given their roles in different secretory processes in different
      tissues, the structural similarity of the three isoforms makes this divergence
      perplexing. Although the neuronal isoform Munc18a is well-established to bind
      tightly to both the closed conformation and the N-peptide of syntaxin 1a, thereby
      inhibiting SNARE complex formation, Munc18b and -c, which have a more widespread
      distribution, are reported to mainly interact with the N-peptide of their
      partnering syntaxins and are thought to instead promote SNARE complex formation.
      We have reinvestigated the interaction between Munc18c and syntaxin 4 (Syx4).
      Using isothermal titration calorimetry, we found that Munc18c, like Munc18a,
      binds to both the closed conformation and the N-peptide of Syx4. Furthermore,
      using a novel kinetic approach, we found that Munc18c, like Munc18a, slows down
      SNARE complex formation through high-affinity binding to syntaxin. This strongly
      suggests that secretory Munc18s in general control the accessibility of the bound
      syntaxin, probably preparing it for SNARE complex assembly.

PMID- 29046355
TI  - Matrix metalloproteinase-7 induces homotypic tumor cell aggregation via
      proteolytic cleavage of the membrane-bound Kunitz-type inhibitor HAI-1.
AB  - Matrix metalloproteinase-7 (MMP-7) plays important roles in tumor progression and
      metastasis. Our previous studies have demonstrated that MMP-7 binds to colon
      cancer cells via cell surface-bound cholesterol sulfate and induces significant
      cell aggregation by cleaving cell-surface protein(s). These aggregated cells
      exhibit a dramatically enhanced metastatic potential. However, the molecular
      mechanism inducing this cell-cell adhesion through the proteolytic action of MMP
      7 remained to be clarified. Here, we explored MMP-7 substrates on the cell
      surface; the proteins on the cell surface were first biotinylated, and a labeled
      protein fragment specifically released from the cells after MMP-7 treatment was
      analyzed using LC-MS/MS. We found that hepatocyte growth factor activator
      inhibitor type 1 (HAI-1), a membrane-bound Kunitz-type serine protease inhibitor,
      is an MMP-7 substrate. We also found that the cell-bound MMP-7 cleaves HAI-1
      mainly between Gly451 and Leu452 and thereby releases the extracellular region as
      soluble HAI-1 (sHAI-1). We further demonstrated that this sHAI-1 can induce
      cancer cell aggregation and determined that the HAI-1 region corresponding to
      amino acids 141-249, which does not include the serine protease inhibitor domain,
      has the cell aggregation-inducing activity. Interestingly, a cell-surface
      cholesterol sulfate-independent proteolytic action of MMP-7 is critical for the
      sHAI-1-mediated induction of cell aggregation, whereas cholesterol sulfate is
      needed for the MMP-7-catalyzed generation of sHAI-1. Considering that MMP-7
      induced cancer cell aggregation is an important mechanism in cancer metastasis,
      we propose that sHAI-1 is an essential component of MMP-7-induced stimulation of
      cancer metastasis and may therefore represent a suitable target for
      antimetastatic therapeutic strategies.

PMID- 29046356
TI  - MicroRNA-302a suppresses influenza A virus-stimulated interferon regulatory
      factor-5 expression and cytokine storm induction.
AB  - During influenza A virus (IAV) infection, cytokine storms play a vital and
      critical role in clinical outcomes. We have previously reported that microRNA
      (miR)-302c regulates IAV-induced IFN expression by targeting the 3'-UTR of
      nuclear factor kappaB (NF-kappaB)-inducing kinase. In the current study, we found
      that miR-302a, another member of the miR-302 cluster, controls the IAV-induced
      cytokine storm. According to results from cell-based and knockout mouse models,
      IAV induces a cytokine storm via interferon regulatory factor-5 (IRF-5). We also
      found that IAV infection up-regulates IRF-5 expression and that IRF-5 in turn
      promotes IAV replication. Furthermore, we observed that IRF-5 is a direct target
      of miR-302a, which down-regulated IRF-5 expression by binding its 3'-UTR.
      Moreover, IAV increased IRF-5 expression by down-regulating miR-302a expression.
      Interestingly, miR-302a inhibited IAV replication. In IAV-infected patients, miR
      302a expression was down-regulated, whereas IRF-5 expression was up-regulated.
      Taken together, our work uncovers and defines a signaling pathway implicated in
      an IAV-induced cytokine storm.

PMID- 29046357
TI  - Structural and thermodynamic analyses reveal critical features of glycopeptide
      recognition by the human PILRalpha immune cell receptor.
AB  - Before entering host cells, herpes simplex virus-1 uses its envelope glycoprotein
      B to bind paired immunoglobulin-like type 2 receptor alpha (PILRalpha) on immune
      cells. PILRalpha belongs to the Siglec (sialic acid (SA)-binding immunoglobulin
      like lectin)-like family, members of which bind SA. PILRalpha is the only Siglec
      member to recognize not only the sialylated O-linked sugar T antigen (sTn) but
      also its attached peptide region. We previously determined the crystal structure
      of PILRalpha complexed with the sTn-linked glycopeptide of glycoprotein B,
      revealing the simultaneous recognition of sTn and peptide by the receptor.
      However, the contribution of each glycopeptide component to PILRalpha binding was
      largely unclear. Here, we chemically synthesized glycopeptide derivatives and
      determined the thermodynamic parameters of their interaction with PILRalpha. We
      show that glycopeptides with different sugar units linking SA and peptides (i.e.
      "GlcNAc-type" and "deoxy-GlcNAc-type" glycopeptides) have lower affinity and more
      enthalpy-driven binding than the wild type (i.e. GalNAc-type glycopeptide). The
      crystal structures of PILRalpha complexed with these glycopeptides highlighted
      the importance of stereochemical positioning of the O4 atom of the sugar moiety.
      These results provide insights both for understanding the unique O-glycosylated
      peptide recognition by the PILRalpha and for the rational design of herpes
      simplex virus-1 entry inhibitors.

PMID- 29046358
TI  - Translationally controlled tumor protein is required for the fast growth of
      Toxoplasma gondii and maintenance of its intracellular development.
AB  - Translationally controlled tumor protein (TCTP) is a highly conserved,
      multifunctional protein that has been implicated in a range of cell physiologic
      processes, especially cell growth and development. A TCTP-like gene has been
      identified in the Toxoplasma genome [ Toxoplasma gondii TCTP ( TgTCTP)], although
      its function remains unknown. The sequence analysis of TgTCTP indicated that it
      is a highly conserved protein in eukaryotes. We found that the expression level
      of TgTCTP in the virulent RH strain was significantly higher than that in the
      avirulent PLK strain. Indirect immunofluorescence showed that TgTCTP was
      expressed in the parasite cytoplasm. The localization of TgTCTP was unchanged
      during the replication of the parasite. We expressed a functional recombinant
      TgTCTP (r TgTCTP) protein in Escherichia coli and found that the recombinant
      protein could form a multimer. We then evaluated the function of TgTCTP using the
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein 9 knockout (KO) system. Phenotypic analysis of the KO strain
      (Delta TgTCTP) revealed that TgTCTP is required for the robust growth of the
      parasites. TgTCTP deficiency also led to early egress of the parasites and
      subsequent impairment in their invasion and attachment abilities. We subsequently
      found that the multimer form of TgTCTP might not be necessary for the growth and
      replication of the parasite. Then the expression profiling of genes in the Delta
      TgTCTP and complement strains were analyzed. The results revealed that 988 genes
      were regulated in Delta TgTCTP compared with the complement strain. Overall,
      although not essential, TgTCTP is required for the fast growth of Tg and
      maintenance of its intracellular development.-Zheng, J., Chen, Y., Li, Z., Cao,
      S., Zhang, Z., Jia, H. Translationally controlled tumor protein is required for
      the fast growth of Toxoplasma gondii and maintenance of its intracellular
      development.

PMID- 29046359
TI  - Androgens trigger different growth responses in genetically identical human hair
      follicles in organ culture that reflect their epigenetic diversity in life.
AB  - Male sex hormones-androgens-regulate male physique development. Without androgen
      signaling, genetic males appear female. During puberty, increasing androgens
      harness the hair follicle's unique regenerative ability to replace many tiny
      vellus hairs with larger, darker terminal hairs ( e.g., beard). Follicle response
      is epigenetically varied: some remain unaffected ( e.g., eyelashes) or are
      inhibited, causing balding. How sex steroid hormones alter such developmental
      processes is unclear, despite high incidences of hormone-driven cancer,
      hirsutism, and alopecia. Unfortunately, existing development models are not
      androgen sensitive. Here, we use hair follicles to establish an androgen
      responsive human organ culture model. We show that women's intermediate facial
      follicles respond to men's higher androgen levels by synthesizing more hair over
      several days, unlike donor-matched, androgen-insensitive, terminal follicles. We
      demonstrate that androgen receptors-androgen-activated gene transcription
      regulators-are required and are present in vivo within these follicles. This is
      the first human organ that involves multiple cell types that responds
      appropriately to hormones in prolonged culture, in a way which mirrors its
      natural behavior. Thus, intermediate hair follicles offer a hormone-switchable
      human model with exceptional, unique availability of genetically identical, but
      epigenetically hormone-insensitive, terminal follicles. This should enable
      advances in understanding sex steroid hormone signaling, gene regulation, and
      developmental and regenerative systems and facilitate better therapies for
      hormone-dependent disorders.-Miranda, B. H., Charlesworth, M. R., Tobin, D. J.,
      Sharpe, D. T., Randall, V. A. Androgens trigger different growth responses in
      genetically identical human hair follicles in organ culture that reflect their
      epigenetic diversity in life.

PMID- 29046361
TI  - Trefoil factor family peptides enhance cell migration by increasing cellular
      osmotic permeability and aquaporin 3 levels.
AB  - Trefoil factor family (TFF) peptides are produced rapidly at sites of injury,
      stimulating epithelial migration, a process involving rapid changes in cell shape
      and volume, requiring rapid flow of water into and out of the cell. We examined
      the effect of TFFs on fluidity of cells by measuring their sensitivity to osmotic
      challenges and cell migration, and determined whether those results were mediated
      through altering the levels of aquaporins (AQPs), a family of transmembrane water
      channels involved in cellular water homeostasis. Gastric (AGS) and colonic (Caco
      2) cell lines had intrinsic TFF levels determined and the predominant TFF peptide
      knocked down (RNA interference). Knockdown caused lessened responsiveness to
      changes in external osmotic challenge (by 51 and 69% in AGS and Caco-2 cells,
      respectively) and reduced cell migration and transepithelial permeability but did
      not influence proliferation. Exogenous TFF increased several AQPs, particularly
      AQP3, and those were reciprocally reduced in knockdown cells. TFF-induced, but
      not fetal calf serum-induced, cell migration was inhibited by the presence of
      AQP3 blocker (CuSO4). We summarize that TFF peptides promptly produced at sites
      of injury increase AQP levels, most notably AQP3, thereby enhancing the cells'
      ability to rapidly change their shape as part of the restitutive process. TFF
      peptides also require functioning AQP3 channels to induce cell migration.
      Marchbank, T., Playford, R. J. Trefoil factor family peptides enhance cell
      migration by increasing cellular osmotic permeability and aquaporin 3 levels.

PMID- 29046360
TI  - A ERK/RSK-mediated negative feedback loop regulates M-CSF-evoked PI3K/AKT
      activation in macrophages.
AB  - Activation of the RAS/ERK and its downstream signaling components is essential
      for growth factor-induced cell survival, proliferation, and differentiation. The
      Src homology-2 domain containing protein tyrosine phosphatase 2 (SHP2), encoded
      by protein tyrosine phosphatase, non-receptor type 11 ( Ptpn11), is a positive
      mediator required for most, if not all, receptor tyrosine kinase-evoked RAS/ERK
      activation, but differentially regulates the PI3K/AKT signaling cascade in
      various cellular contexts. The precise mechanisms underlying the differential
      effects of SHP2 deficiency on the PI3K pathway remain unclear. We found that mice
      with myelomonocytic cell-specific [ Tg(LysM-Cre); Ptpn11fl/fl mice] Ptpn11
      deficiency exhibit mild osteopetrosis. SHP2-deficient bone marrow macrophages
      (BMMs) showed decreased proliferation in response to M-CSF and decreased
      osteoclast generation. M-CSF-evoked ERK1/2 activation was decreased, whereas AKT
      activation was enhanced in SHP2-deficient BMMs. ERK1/2, via its downstream target
      RSK2, mediates this negative feedback by negatively regulating phosphorylation of
      M-CSF receptor at Tyr721 and, consequently, its binding to p85 subunit of PI3K
      and PI3K activation. Pharmacologic inhibition of RSK or ERK phenotypically mimics
      the signaling defects observed in SHP2-deficient BMMs. Furthermore, this increase
      in PI3K/AKT activation enables BMM survival in the setting of SHP2 deficiency.
      Wang, L., Iorio, C., Yan, K., Yang, H., Takeshita, S., Kang, S., Neel, B.G.,
      Yang, W. An ERK/RSK-mediated negative feedback loop regulates M-CSF-evoked
      PI3K/AKT activation in macrophages.

PMID- 29046363
TI  - Serum neurofilament light is sensitive to active cerebral small vessel disease.
AB  - OBJECTIVE: To explore whether serum neurofilament light chain protein (NfL)
      levels are increased in patients with MRI-confirmed recent small subcortical
      infarcts (RSSI) compared to healthy controls and to determine the subsequent
      course and determinants of NfL levels in a longitudinal manner. METHODS: In a
      prospectively collected group of symptomatic patients with an RSSI (n = 79, mean
      age 61 +/- 11 years, 67% male), we analyzed brain MRI and serum NfL using a
      Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after
      stroke. Community-dwelling healthy age- and sex-matched individuals with
      comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as
      controls. RESULTS: Patients with an RSSI had higher NfL baseline levels compared
      to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher
      with the time from stroke symptom onset to blood sampling (median 4 days, range 1
      11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month
      follow-up but returned to normal at 15 months after stroke. NfL levels were
      associated with RSSI size and baseline WMH severity and were especially high in
      patients with new, clinically silent cerebral small vessel disease (CSVD)-related
      lesions at follow-up. CONCLUSIONS: Serum NfL is increased in patients with an
      RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically
      silent. This suggests NfL as a blood biomarker for active CSVD.

PMID- 29046364
TI  - Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone
      for migraine.
AB  - OBJECTIVE: To determine outcomes among patients with migraine in the emergency
      department (ED) who receive IV hydromorphone vs IV prochlorperazine +
      diphenhydramine. METHODS: This study was conducted in 2 EDs in New York City.
      Patients who met international criteria for migraine were eligible for
      participation if they had not used an opioid within the previous month.
      Clinicians, participants, investigators, and research personnel were blinded to
      treatment. Patients were randomized in blocks of 4. Participants received
      hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg.
      Diphenhydramine was administered to prevent akathisia, a common side effect of IV
      prochlorperazine. The primary outcome was sustained headache relief, defined as
      achieving a headache level of mild or none within 2 hours of medication
      administration and maintaining that level for 48 hours without the requirement of
      rescue medication. A planned interim analysis was conducted once 48-hour data
      were available for 120 patients. RESULTS: The trial was halted by the data
      monitoring committee after 127 patients had been enrolled. The primary outcome
      was achieved in the prochlorperazine arm by 37 of 62 (60%) participants and in
      the hydromorphone arm by 20 of 64 (31%) participants (difference 28%, 95%
      confidence interval 12-45, number needed to treat 4, 95% confidence interval 2
      9). CONCLUSIONS: IV hydromorphone is substantially less effective than IV
      prochlorperazine for the treatment of acute migraine in the ED and should not be
      used as first-line therapy. CLINICALTRIALSGOV IDENTIFIER: NCT02389829.
      CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for
      patients in the ED with migraine, IV prochlorperazine + diphenhydramine is
      superior to IV hydromorphone.

PMID- 29046365
TI  - Amyloid PET scan: Staging beyond reading?

PMID- 29046366
TI  - Long non-coding RNA PVT1 indicates a poor prognosis of glioma and promotes cell
      proliferation and invasion via target EZH2.
AB  - Human glioma is one of the malignant tumors of the central nervous system (CNS).
      Its prognosis is poor, which is due to its genetic heterogeneity and our poor
      understanding of its underlying molecular mechanisms. The present study aimed to
      assess the relationship between plasmacytoma variant translocation 1 (PVT1) and
      enhancer of zeste homolog 2 (EZH2), and their effects on the proliferation and
      invasion of glioma cells. The expression levels of PVT1 and EZH2 in human glioma
      tissues and cell lines were measured using quantitative RT-PCR (qRT-PCR). Then,
      after siRNA-PVT1 and entire PVT1 sequence vector transfection, we determined the
      regulation roles of PVT1 in the proliferation, apoptosis, migration, and invasion
      of glioma cells. We found that the expression levels of both PVT1 and EZH2 were
      up-regulated in human glioma tissues and cell lines, and positively correlated
      with glioma malignancy. And, silencing of PVT1 expression resulted in decreased
      proliferation, increased apoptosis, and decreased migration and invasion. In
      addition, exogenous PVT1 led to increased EZH2 expression and increased
      proliferation and induced proliferation and invasion. These data inferred that
      long non-coding RNA PVT1 could be served as an indicator of glioma prognosis, and
      PVT1-EZH2 regulatory pathway may be a novel therapeutic target for treating
      glioma.

PMID- 29046362
TI  - In vivo staging of regional amyloid deposition.
AB  - OBJECTIVES: To estimate a regional progression pattern of amyloid deposition from
      cross-sectional amyloid-sensitive PET data and evaluate its potential for in vivo
      staging of an individual's amyloid pathology. METHODS: Multiregional analysis of
      florbetapir (18F-AV45)-PET data was used to determine individual amyloid
      distribution profiles in a sample of 667 participants from the Alzheimer's
      Disease Neuroimaging Initiative cohort, including cognitively normal older
      individuals (CN) as well as patients with mild cognitive impairment and Alzheimer
      disease (AD) dementia. The frequency of regional amyloid positivity across CN
      individuals was used to construct a 4-stage model of progressing amyloid
      pathology, and individual distribution profiles were used to evaluate the
      consistency of this hierarchical stage model across the full cohort. RESULTS:
      According to a 4-stage model, amyloid deposition begins in temporobasal and
      frontomedial areas, and successively affects the remaining associative neocortex,
      primary sensory-motor areas and the medial temporal lobe, and finally the
      striatum. Amyloid deposition in these brain regions showed a highly consistent
      hierarchical nesting across participants, where only 2% exhibited distribution
      profiles that deviated from the staging scheme. The earliest in vivo amyloid
      stages were mostly missed by conventional dichotomous classification approaches
      based on global florbetapir-PET signal, but were associated with significantly
      reduced CSF Abeta42 levels. Advanced in vivo amyloid stages were most frequent in
      patients with AD and correlated with cognitive impairment in individuals without
      dementia. CONCLUSIONS: The highly consistent regional hierarchy of PET-evidenced
      amyloid deposition across participants resembles neuropathologic observations and
      suggests a predictable regional sequence that may be used to stage an
      individual's progress of amyloid pathology in vivo.

PMID- 29046367
TI  - PKCdelta silencing alleviates saturated fatty acid induced ER stress by enhancing
      SERCA activity.
AB  - Protein kinase C delta (PKCdelta) plays an important role in nonalcoholic fatty
      liver disease (NAFLD), however, the mechanism remains unknown. The present study
      explored the role of PKCdelta in NAFLD development and investigated the
      relationships between PKCdelta, calcium homeostasis, and endoplasmic reticulum
      (ER) stress (ERS). Hepatic steatosis cell model was induced by palmitic acid (PA)
      in L02 cells. Lipid accretion was evaluated using Oil Red O staining and a
      triglyceride (TG) detection kit. PKCdelta was down-regulated by siRNA. RT-PCR and
      Western blotting were used to detect the expression of ERS markers. The
      fluorescence of Ca2+ influx was recorded using confocal microscopy. Sarco-ER Ca2+
      ATPase (SERCA) activity was measured by ultramicro-ATP enzyme test kit. PA
      treatment induced lipid accretion in L02 cells, destroyed the ER structure, and
      increased PKCdelta activation in a time-dependent manner. Further, PA treatment
      significantly increased the expression of ERS markers, Ig heavy chain binding
      protein (Bip), and homologous proteins of CCAAT-enhancer binding proteins (CHOP).
      PKCdelta silencing down-regulated Bip and CHOP expression, indicating a
      successful alleviation of ERS. The increased calcium storage induced by PA
      stimulation was significantly decreased in L02 cells treated with PKCdelta siRNA
      compared with the negative control. Moreover, diminished SERCA activity caused by
      PA was recovered in PKCdelta siRNA transfected cells. To the best of our
      knowledge, this is the first report demonstrating that the inhibition of PKCdelta
      alleviates ERS by enhancing SERCA activity and stabilizing calcium homeostasis.

PMID- 29046369
TI  - Structural and functional studies of SAV0551 from Staphylococcus aureus as a
      chaperone and glyoxalase III.
AB  - The DJ-1/ThiJ/PfpI superfamily of proteins is highly conserved across all
      biological kingdoms showing divergent multifunctions, such as chaperone,
      catalase, protease, and kinase. The common theme of these functions is responding
      to and managing various cellular stresses. DJ-1/ThiJ/PfpI superfamily members are
      classified into three subfamilies according to their quaternary structure (DJ-1-,
      YhbO-, and Hsp-types). The Hsp-type subfamily includes Hsp31, a chaperone and
      glyoxalase III. SAV0551, an Hsp-type subfamily member from Staphylococcus aureus,
      is a hypothetical protein that is predicted as Hsp31. Thus, to reveal the
      function and reaction mechanism of SAV0551, the crystal structure of SAV0551 was
      determined. The overall folds in SAV0551 are similar to other members of the Hsp
      type subfamily. We have shown that SAV0551 functions as a chaperone and that the
      surface structure is crucial for holding unfolded substrates. As many DJ
      1/ThiJ/PfpI superfamily proteins have been characterized as glyoxalase III, our
      study also demonstrates SAV0551 as a glyoxalase III that is independent of any
      cofactors. The reaction mechanism was evaluated via a glyoxylate-bound structure
      that mimics the hemithioacetal reaction intermediate. We have confirmed that the
      components required for reaction are present in the structure, including a
      catalytic triad for a catalytic action, His78 as a base, and a water molecule for
      hydrolysis. Our functional studies based on the crystal structures of native and
      glyoxylate-bound SAV0551 will provide a better understanding of the reaction
      mechanism of a chaperone and glyoxalase III.

PMID- 29046368
TI  - Enhancement of lung gene delivery after aerosol: a new strategy using non-viral
      complexes with antibacterial properties.
AB  - The pathophysiology of obstructive pulmonary diseases, such as cystic fibrosis
      (CF), leads to the development of chronic infections in the respiratory tract.
      Thus, the symptomatic management of the disease requires, in particular,
      repetitive antibiotherapy. Besides these antibacterial treatments, certain
      pathologies, such as CF or chronic obstructive pulmonary disease (COPD), require
      the intake of many drugs. This simultaneous absorption may lead to undesirable
      drug interactions. For example, Orkambi(r) (lumacaftor/Ivacaftor, Vertex), a
      pharmacological drug employed to treat F508del patients, cannot be used with
      antibiotics such as rifampicin or rifabutin (rifamycin family) which are
      necessary to treat Mycobacteriaceae. As far as gene therapy is concerned,
      bacteria and/or biofilm in the airways present an additional barrier for gene
      transfer. Thus, aerosol administration of nanoparticles have to overcome many
      obstacles before allowing cellular penetration of therapeutic compounds. This
      review focusses on the development of aerosol formulations adapted to the
      respiratory tract and its multiple barriers. Then, formulations that are
      currently used in clinical applications are summarized depending on the active
      molecule delivered. Finally, we focus on new therapeutic approaches to reduce
      possible drug interactions by transferring the antibacterial activity to the
      nanocarrier while ensuring the transfection efficiency.

PMID- 29046371
TI  - Low heritability of nest construction in a wild bird.
AB  - In birds and other taxa, nest construction varies considerably between and within
      populations. Such variation is hypothesized to have an adaptive (i.e. genetic)
      basis, but estimates of heritability in nest construction are largely lacking.
      Here, we demonstrate with data collected over 10 years from 1010 nests built by
      blue tits in nest-boxes that nest size (height of nest material) and nest
      composition (proportion of feathers in the nest) are repeatable but only weakly
      (12-13%) heritable female traits. These findings imply that nest construction may
      evolve but only if subjected to strong and consistent selection pressures.

PMID- 29046370
TI  - Excessive glucocorticoid-induced muscle MuRF1 overexpression is independent of
      Akt/FoXO1 pathway.
AB  - The ubiquitin-proteasome system (UPS)-dependent proteolysis plays a major role in
      the muscle catabolic action of glucocorticoids (GCs). Atrogin-1 and muscle
      specific RING finger protein 1 (MuRF1), two E3 ubiquitin ligases, are uniquely
      expressed in muscle. It has been previously demonstrated that GC treatment
      induced MuRF1 and atrogin-1 overexpression. However, it is yet unclear whether
      the higher pharmacological dose of GCs induced muscle protein catabolism through
      MuRF1 and atrogin-1. In the present study, the role of atrogin-1 and MuRF1 in
      C2C12 cells protein metabolism during excessive dexamethasone (DEX) was studied.
      The involvement of Akt/forkhead box O1 (FoXO1) signaling pathway and the cross
      talk between anabolic regulator mammalian target of rapamycin (mTOR) and
      catabolic regulator FoXO1 were investigated. High concentration of DEX increased
      MuRF1 protein level in a time-dependent fashion (P<0.05), while had no detectable
      effect on atrogin-1 protein (P>0.05). FoXO1/3a (Thr24/32) phosphorylation was
      enhanced (P<0.05), mTOR phosphorylation was suppressed (P<0.05), while Akt
      protein expression was not affected (P>0.05) by DEX. RU486 treatment inhibited
      the DEX-induced increase of FoXO1/3a phosphorylation (P<0.05) and MuRF1 protein;
      LY294002 (LY) did not restore the stimulative effect of DEX on the FoXO1/3a
      phosphorylation (P>0.05), but inhibited the activation of MuRF1 protein induced
      by DEX (P<0.05); rapamycin (RAPA) inhibited the stimulative effect of DEX on the
      FoXO1/3a phosphorylation and MuRF1 protein (P<0.05).

PMID- 29046372
TI  - Stressful city sounds: glucocorticoid responses to experimental traffic noise are
      environmentally dependent.
AB  - A major challenge in urban ecology is to identify the environmental factors
      responsible for phenotypic differences between urban and rural individuals.
      However, the intercorrelation between the factors that characterize urban
      environments, combined with a lack of experimental manipulations of these factors
      in both urban and rural areas, hinder efforts to identify which aspects of urban
      environments are responsible for phenotypic differences. Among the factors
      modified by urbanization, anthropogenic sound, particularly traffic noise, is
      especially detrimental to animals. The mechanisms by which anthropogenic sound
      affects animals are unclear, but one potential mechanism is through changes in
      glucocorticoid hormone levels. We exposed adult house wrens, Troglodytes aedon,
      to either traffic noise or pink noise (a non-traffic noise control). We found
      that urban wrens had higher initial (pre-restraint) corticosterone than rural
      wrens before treatment, and that traffic noise elevated initial corticosterone of
      rural, but not urban, wrens. By contrast, restraint stress-induced corticosterone
      was not affected by noise treatment. Our results indicate that traffic noise
      specifically contributes to determining the glucocorticoid phenotype, and suggest
      that glucocorticoids are a mechanism by which anthropogenic sound causes
      phenotypic differences between urban and rural animals.

PMID- 29046373
TI  - O brother, where art thou? Investment in siblings for inclusive fitness benefits,
      not father absence, predicts earlier age at menarche.
AB  - Numerous studies have indicated that father absence is associated with earlier
      age at menarche, with many evolutionary theories assuming that father absence is
      a causal factor that accelerates reproductive development. However, an
      alternative interpretation suggests that offspring may reproduce earlier in the
      presence of half- or step-siblings as the indirect fitness benefits to investing
      in them are lower, relative to delaying reproduction and investing in full
      siblings. From this perspective, father absence may perform no causal role in
      facilitating the onset of menarche. Using data from the Avon Longitudinal Study
      of Parents and Children, I find that individuals with only half- or step-siblings
      reach reproductive age earlier than those with only full siblings, with no
      independent effect of father absence. These results suggest that inclusive
      fitness benefits to investing in siblings, rather than father absence, may
      predict variation in age at menarche. These results provide a greater
      understanding of the adaptive mechanisms involved in reproductive decision
      making, as well as potential implications for human life-history evolution and
      cooperative breeding more broadly.

PMID- 29046375
TI  - Left-right asymmetry of the Maxwell spot centroids in adults without and with
      dyslexia.
AB  - In human vision, the brain has to select one view of the world from our two eyes.
      However, the existence of a clear anatomical asymmetry providing an initial
      imbalance for normal neural development is still not understood. Using a so
      called foveascope, we found that for a cohort of 30 normal adults, the two blue
      cone-free areas at the centre of the foveas are asymmetrical. The noise
      stimulated afterimage dominant eye introduced here corresponds to the circular
      blue cone-free area, while the non-dominant eye corresponds to the diffuse and
      irregular elliptical outline. By contrast, we found that this asymmetry is absent
      or frustrated in a similar cohort of 30 adults with normal ocular status, but
      with dyslexia, i.e. with visual and phonological deficits. In this case, our
      results show that the two Maxwell centroid outlines are both circular but lead to
      an undetermined afterimage dominance with a coexistence of primary and mirror
      images. The interplay between the lack of asymmetry and the development in the
      neural maturation of the brain pathways suggests new implications in both
      fundamental and biomedical sciences.

PMID- 29046374
TI  - A multivariate test of disease risk reveals conditions leading to disease
      amplification.
AB  - Theory predicts that increasing biodiversity will dilute the risk of infectious
      diseases under certain conditions and will amplify disease risk under others.
      Yet, few empirical studies demonstrate amplification. This contrast may occur
      because few studies have considered the multivariate nature of disease risk,
      which includes richness and abundance of parasites with different transmission
      modes. By combining a multivariate statistical model developed for biodiversity
      ecosystem-multifunctionality with an extensive field manipulation of host (plant)
      richness, composition and resource supply to hosts, we reveal that (i) host
      richness alone could not explain most changes in disease risk, and (ii) shifting
      host composition allowed disease amplification, depending on parasite
      transmission mode. Specifically, as predicted from theory, the effect of host
      diversity on parasite abundance differed for microbes (more density-dependent
      transmission) and insects (more frequency-dependent transmission). Host diversity
      did not influence microbial parasite abundance, but nearly doubled insect
      parasite abundance, and this amplification effect was attributable to variation
      in host composition. Parasite richness was reduced by resource addition, but only
      in species-rich host communities. Overall, this study demonstrates that multiple
      drivers, related to both host community and parasite characteristics, can
      influence disease risk. Furthermore, it provides a framework for evaluating
      multivariate disease risk in other systems.

PMID- 29046376
TI  - Functional basis of the sexual dimorphism in the auditory fovea of the duetting
      bushcricket Ancylecha fenestrata.
AB  - From mammals to insects, acoustic communication is in many species crucial for
      successful reproduction. In the duetting bushcricket Ancylecha fenestrata, the
      mutual acoustic communication between males and females is asymmetrical. We
      investigated how those signalling disparities are reflected by sexual dimorphism
      of their ears. Both sexes have tympanic ears in their forelegs, but male ears
      possess a significantly longer crista acustica containing 35% more scolopidia.
      With more sensory cells to cover a similar hearing range, the male hearing organ
      shows a significantly expanded auditory fovea that is tuned to the dominant
      frequency of the female reply to facilitate phonotactic mate finding. This sex
      specific auditory fovea is demonstrated in the mechanical and neuronal responses
      along the tonotopically organized crista acustica by laservibrometric and
      electrophysiological frequency mapping, respectively. Morphometric analysis of
      the crista acustica revealed an interrupted gradient in organ height solely
      within this auditory fovea region, whereas all other anatomical parameters
      decrease continuously from proximal to distal. Combining behavioural, anatomical,
      biomechanical and neurophysiological information, we demonstrate evidence of a
      pronounced auditory fovea as a sex-specific adaptation of an insect hearing organ
      for intraspecific acoustic communication.

PMID- 29046377
TI  - Morphospaces of functionally analogous traits show ecological separation between
      birds and pterosaurs.
AB  - Birds originated and radiated in the presence of another group of flying
      vertebrates, the pterosaurs. Opinion is divided as to whether birds competitively
      displaced pterosaurs from small-body size niches or whether the two groups
      coexisted with little competition. Previous studies of Mesozoic birds and
      pterosaurs compared measurements of homologous limb bones to test these
      hypotheses. However, these characters probably reflect differing ancestries
      rather than ecologies. Here, competition and ecological separation were tested
      for using multivariate analyses of functionally equivalent morphological
      characters. As well as using characters from the fore- and hindlimbs, these
      analyses also included measurements of the lower jaw. The results of this study
      indicate that pterosaurs had relatively longer jaws, shorter metatarsals and
      shorter brachial regions compared with birds of similar size. Contrary to the
      results of previous studies, the distal wing was not important for separating the
      two clades in morphospace owing to the inclusion of the primary feathers in this
      unit. The differences found here indicate ecological separation based on
      differences in size, locomotory features and feeding adaptations. Thus, instead
      of one group displacing the other, birds and pterosaurs appear to have adopted
      distinctive ecological strategies throughout their period of coexistence.

PMID- 29046378
TI  - Fluctuating seawater pH/pCO2 regimes are more energetically expensive than static
      pH/pCO2 levels in the mussel Mytilus edulis.
AB  - Ocean acidification (OA) studies typically use stable open-ocean pH or CO2
      values. However, species living within dynamic coastal environments can naturally
      experience wide fluctuations in abiotic factors, suggesting their responses to
      stable pH conditions may not be reflective of either present or near-future
      conditions. Here we investigate the physiological responses of the mussel Mytilus
      edulis to variable seawater pH conditions over short- (6 h) and medium-term (2
      weeks) exposures under both current and near-future OA scenarios. Mussel
      haemolymph pH closely mirrored that of seawater pH over short-term changes of 1
      pH unit with acidosis or recovery accordingly, highlighting a limited capacity
      for acid-base regulation. After 2 weeks, mussels under variable pH conditions had
      significantly higher metabolic rates, antioxidant enzyme activities and lipid
      peroxidation than those exposed to static pH under both current and near-future
      OA scenarios. Static near-future pH conditions induced significant acid-base
      disturbances and lipid peroxidation compared with the static present-day
      conditions but did not affect the metabolic rate. These results clearly
      demonstrate that living in naturally variable environments is energetically more
      expensive than living in static seawater conditions, which has consequences for
      how we extrapolate future OA responses in coastal species.

PMID- 29046379
TI  - Heterospecific eavesdropping in ant-following birds of the Neotropics is a
      learned behaviour.
AB  - Animals eavesdrop on other species to obtain information about their
      environments. Heterospecific eavesdropping can yield tangible fitness benefits by
      providing valuable information about food resources and predator presence. The
      ability to eavesdrop may therefore be under strong selection, although extensive
      research on alarm-calling in avian mixed-species flocks has found only limited
      evidence that close association with another species could select for innate
      signal recognition. Nevertheless, very little is known about the evolution of
      eavesdropping behaviour and the mechanism of heterospecific signal recognition,
      particularly in other ecological contexts, such as foraging. To understand
      whether heterospecific eavesdropping was an innate or learned behaviour in a
      foraging context, we studied heterospecific signal recognition in ant-following
      birds of the Neotropics, which eavesdrop on vocalizations of obligate ant
      following species to locate and recruit to swarms of the army ant Eciton
      burchellii, a profitable food resource. We used a playback experiment to compare
      recruitment of ant-following birds to vocalizations of two obligate species at a
      mainland site (where both species are present) and a nearby island site (where
      one species remains whereas the other went extinct approx. 40 years ago). We
      found that ant-following birds recruited strongly to playbacks of the obligate
      species present at both island and mainland sites, but the island birds did not
      recruit to playbacks of the absent obligate species. Our results strongly suggest
      that (i) ant-following birds learn to recognize heterospecific vocalizations from
      ecological experience and (ii) island birds no longer recognize the locally
      extinct obligate species after eight generations of absence from the island.
      Although learning appears to be the mechanism of heterospecific signal
      recognition in ant-following birds, more experimental tests are needed to fully
      understand the evolution of eavesdropping behaviour.

PMID- 29046380
TI  - Re-evaluating the link between brain size and behavioural ecology in primates.
AB  - Comparative studies have identified a wide range of behavioural and ecological
      correlates of relative brain size, with results differing between taxonomic
      groups, and even within them. In primates for example, recent studies contradict
      one another over whether social or ecological factors are critical. A basic
      assumption of such studies is that with sufficiently large samples and
      appropriate analysis, robust correlations indicative of selection pressures on
      cognition will emerge. We carried out a comprehensive re-examination of
      correlates of primate brain size using two large comparative datasets and
      phylogenetic comparative methods. We found evidence in both datasets for
      associations between brain size and ecological variables (home range size, diet
      and activity period), but little evidence for an effect of social group size, a
      correlation which has previously formed the empirical basis of the Social Brain
      Hypothesis. However, reflecting divergent results in the literature, our results
      exhibited instability across datasets, even when they were matched for species
      composition and predictor variables. We identify several potential empirical and
      theoretical difficulties underlying this instability and suggest that these
      issues raise doubts about inferring cognitive selection pressures from
      behavioural correlates of brain size.

PMID- 29046382
TI  - The erroneous signals of detection theory.
AB  - Signal detection theory has influenced the behavioural sciences for over 50
      years. The theory provides a simple equation that indicates numerous 'intuitive'
      results; e.g. prey should be more prone to take evasive action (in response to an
      ambiguous cue) if predators are more common. Here, we use analytical and
      computational models to show that, in numerous biological scenarios, the standard
      results of signal detection theory do not apply; more predators can result in
      prey being less responsive to such cues. The standard results need not apply when
      the probability of danger pertains not just to the present, but also to future
      decisions. We identify how responses to risk should depend on background
      mortality and autocorrelation, and that predictions in relation to animal welfare
      can also be reversed from the standard theory.

PMID- 29046381
TI  - Trunk dental tissue evolved independently from underlying dermal bony plates but
      is associated with surface bones in living odontode-bearing catfish.
AB  - Although oral dental tissue is a vertebrate attribute, trunk dental tissue
      evolved in several extinct vertebrate lineages but is rare among living species.
      The question of which processes trigger dental-tissue formation in the trunk
      remains open, and would shed light on odontogenesis evolution. Extra-oral dental
      structures (odontodes) in the trunk are associated with underlying dermal bony
      plates, leading us to ask whether the formation of trunk bony plates is necessary
      for trunk odontodes to emerge. To address this question, we focus on
      Loricarioidei: an extant, highly diverse group of catfish whose species all have
      odontodes. We examined the location and cover of odontodes and trunk dermal bony
      plates for all six loricarioid families and 17 non-loricarioid catfish families
      for comparison. We inferred the phylogeny of Loricarioidei using a new 10-gene
      dataset, eight time-calibration points, and noise-reduction techniques. Based on
      this phylogeny, we reconstructed the ancestral states of odontode and bony plate
      cover, and find that trunk odontodes emerged before dermal bony plates in
      Loricarioidei. Yet we discovered that when bony plates are absent, other surface
      bones are always associated with odontodes, suggesting a link between osteogenic
      and odontogenic developmental pathways, and indicating a remarkable trunk
      odontogenic potential in Loricarioidei.

PMID- 29046383
TI  - Preservation of uropygial gland lipids in a 48-million-year-old bird.
AB  - Although various kinds of organic molecules are known to occur in fossils and
      rocks, most soft tissue preservation in animals is attributed to melanin or
      porphyrins. Lipids are particularly stable over time-as diagenetically altered
      'geolipids' or as major molecular constituents of kerogen or fossil 'geopolymers'
      and may be expected to be preserved in certain vertebrate tissues. Here we
      analysed lipid residues from the uropygial gland of an early Eocene bird using
      pyrolysis gas chromatography mass spectroscopy. We found a pattern of aliphatic
      molecules in the fossil gland that was distinct from the host oil shale sediment
      matrix and from feathers of the same fossil. The fossil gland contained abundant
      n-alkenes, n-alkanes and alkylbenzenes with chain lengths greater than 20, as
      well as functionalized long-chain aldehydes, ketones, alkylnitriles and
      alkylthiophenes that were not detected in host sediment or fossil feathers. By
      comparison with modern bird uropygial gland wax esters, we show that these
      molecular fossils are likely derived from endogenous wax ester fatty alcohols and
      fatty acids that survived initial decay and underwent early diagenetic
      geopolymerization. These data demonstrate the high fidelity preservation of the
      uropygial gland waxes and showcase the resilience of lipids over geologic time
      and their potential role in the exceptional preservation of lipid-rich tissues of
      macrofossils.

PMID- 29046384
TI  - Temperate marine protected area provides recruitment subsidies to local
      fisheries.
AB  - The utility of marine protected areas (MPAs) as a means of protecting exploited
      species and conserving biodiversity within MPA boundaries is supported by strong
      empirical evidence. However, the potential contribution of MPAs to fished
      populations beyond their boundaries is still highly controversial; empirical
      measures are scarce and modelling studies have produced a range of predictions,
      including both positive and negative effects. Using a combination of genetic
      parentage and relatedness analysis, we measured larval subsidies to local
      fisheries replenishment for Australasian snapper (Chrysophrys auratus: Sparidae)
      from a small (5.2 km2), well-established, temperate, coastal MPA in northern New
      Zealand. Adult snapper within the MPA contributed an estimated 10.6% (95% CI: 5.5
      18.1%) of newly settled juveniles to surrounding areas (approx. 400 km2), with no
      decreasing trend in contributions up to 40 km away. Biophysical modelling of
      larval dispersal matched experimental data, showing larvae produced inside the
      MPA dispersed over a comparable distance. These results demonstrate that
      temperate MPAs have the potential to provide recruitment subsidies at magnitudes
      and spatial scales relevant to fisheries management. The validated biophysical
      model provides a cost-efficient opportunity to generalize these findings to other
      locations and climate conditions, and potentially informs the design of MPA
      networks for enhancing fisheries management.

PMID- 29046385
TI  - Trisomy 13 and 18: Cardiac Surgery Makes Sense if It Is Part of a Comprehensive
      Care Strategy.

PMID- 29046386
TI  - Social Determinants of Health and Hospital Readmission.

PMID- 29046387
TI  - Congenital Heart Surgery on In-Hospital Mortality in Trisomy 13 and 18.
AB  - BACKGROUND AND OBJECTIVES: Congenital heart disease (CHD) is common in trisomy 13
      (T13) and trisomy 18 (T18), but surgical repair has not been offered in most
      centers. Data on outcomes of congenital heart surgery (CHS) for T13 and T18 are
      lacking. We sought to determine the impact of CHS on in-hospital mortality in T13
      and T18. METHODS: Data from the 2004 to 2015 Pediatric Health Information System
      database were used to identify inpatients with T13 or T18 and CHD. Data were
      restricted to newborns with T13 or T18 admitted at <=14 days of age. Hospital
      readmissions were examined to analyze longer-term in-hospital mortality. In
      hospital mortality and length of stay were compared between infants with and
      without CHD and with and without CHS. RESULTS: The study cohort included 1020
      infants with T18 and 648 infants with T13. CHD was present in 91% of infants with
      T18 and 86% of infants with T13. CHS was performed in 7% of each group. In
      hospital mortality was decreased in those who underwent CHS (64% lower in T18 [P
      <.001]; 45% lower in T13 [P = .003]) and remained decreased throughout the 24
      months of follow-up. In-hospital mortality was decreased in infants with higher
      weight, female sex, and older age at admission. CONCLUSIONS: CHS is associated
      with decreased in-hospital mortality in T18 and T13. These results suggest CHS
      may be beneficial in select cases.

PMID- 29046388
TI  - The Early Dendritic Cell Signaling Induced by Virulent Francisella tularensis
      Strain Occurs in Phases and Involves the Activation of Extracellular Signal
      Regulated Kinases (ERKs) and p38 In the Later Stage.
AB  - Dendritic cells (DCs) infected by Francisella tularensis are poorly activated and
      do not undergo classical maturation process. Although reasons of such
      unresponsiveness are not fully understood, their impact on the priming of
      immunity is well appreciated. Previous attempts to explain the behavior of
      Francisella-infected DCs were hypothesis-driven and focused on events at later
      stages of infection. Here, we took an alternative unbiased approach by applying
      methods of global phosphoproteomics to analyze the dynamics of cell signaling in
      primary DCs during the first hour of infection by Francisella tularensis
      Presented results show that the early response of DCs to Francisella occurs in
      phases and that ERK and p38 signaling modules induced at the later stage are
      differentially regulated by virulent and attenuated DeltadsbA strain. These
      findings imply that the temporal orchestration of host proinflammatory pathways
      represents the integral part of Francisella life-cycle inside hijacked DCs.

PMID- 29046389
TI  - The Antibody Repertoire of Colorectal Cancer.
AB  - Immunotherapy is becoming increasingly important in the fight against cancers,
      using and manipulating the body's immune response to treat tumors. Understanding
      the immune repertoire-the collection of immunological proteins-of treated and
      untreated cells is possible at the genomic, but technically difficult at the
      protein level. Standard protein databases do not include the highly divergent
      sequences of somatic rearranged immunoglobulin genes, and may lead to miss
      identifications in a mass spectrometry search. We introduce a novel proteogenomic
      approach, AbScan, to identify these highly variable antibody peptides, by
      developing a customized antibody database construction method using RNA-seq reads
      aligned to immunoglobulin (Ig) genes.AbScan starts by filtering transcript (RNA
      seq) reads that match the template for Ig genes. The retained reads are used to
      construct a repertoire graph using the "split" de Bruijn graph: a graph structure
      that improves on the standard de Bruijn graph to capture the high diversity of Ig
      genes in a compact manner. AbScan corrects for sequencing errors, and converts
      the graph to a format suitable for searching with MS/MS search tools. We used
      AbScan to create an antibody database from 90 RNA-seq colorectal tumor samples.
      Next, we used proteogenomic analysis to search MS/MS spectra of matched
      colorectal samples from the Clinical Proteomic Tumor Analysis Consortium (CPTAC)
      against the AbScan generated database. AbScan identified 1,940 distinct antibody
      peptides. Correlating with previously identified Single Amino-Acid Variants
      (SAAVs) in the tumor samples, we identified 163 pairs (antibody peptide, SAAV)
      with significant cooccurrence pattern in the 90 samples. The presence of
      coexpressed antibody and mutated peptides was correlated with survival time of
      the individuals. Our results suggest that AbScan
      (https://github.com/csw407/AbScan.git) is an effective tool for a proteomic
      exploration of the immune response in cancers.

PMID- 29046390
TI  - Novel Sarcopenia-related Alterations in Sarcomeric Protein Post-translational
      Modifications (PTMs) in Skeletal Muscles Identified by Top-down Proteomics.
AB  - Sarcopenia, the age-related loss of skeletal muscle mass and strength, is a
      significant cause of morbidity in the elderly and is a major burden on health
      care systems. Unfortunately, the underlying molecular mechanisms in sarcopenia
      remain poorly understood. Herein, we utilized top-down proteomics to elucidate
      sarcopenia-related changes in the fast- and slow-twitch skeletal muscles of aging
      rats with a focus on the sarcomeric proteome, which includes both myofilament and
      Z-disc proteins-the proteins that constitute the contractile apparatuses. Top
      down quantitative proteomics identified significant changes in the post
      translational modifications (PTMs) of critical myofilament proteins in the fast
      twitch skeletal muscles of aging rats, in accordance with the vulnerability of
      fast-twitch muscles to sarcopenia. Surprisingly, age-related alterations in the
      phosphorylation of Cypher isoforms, proteins that localize to the Z-discs in
      striated muscles, were also noted in the fast-twitch skeletal muscle of aging
      rats. This represents the first report of changes in the phosphorylation of Z
      disc proteins in skeletal muscle during aging. In addition, increased
      glutathionylation of slow skeletal troponin I, a novel modification that may help
      protect against oxidative damage, was observed in slow-twitch skeletal muscles.
      Furthermore, we have identified and characterized novel muscle type-specific
      proteoforms of myofilament proteins and Z-disc proteins, including a novel
      isoform of the Z-disc protein Enigma. The finding that the phosphorylation of Z
      disc proteins is altered in response to aging in the fast-twitch skeletal muscles
      of aging rats opens new avenues for the investigation of the role of Z-discs in
      age-related muscle dysfunction.

PMID- 29046391
TI  - GPI-anchored proteins are confined in subdiffraction clusters at the apical
      surface of polarized epithelial cells.
AB  - Spatio-temporal compartmentalization of membrane proteins is critical for the
      regulation of diverse vital functions in eukaryotic cells. It was previously
      shown that, at the apical surface of polarized MDCK cells,
      glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are organized in
      small cholesterol-independent clusters of single GPI-AP species (homoclusters),
      which are required for the formation of larger cholesterol-dependent clusters
      formed by multiple GPI-AP species (heteroclusters). This clustered organization
      is crucial for the biological activities of GPI-APs; hence, understanding the
      spatio-temporal properties of their membrane organization is of fundamental
      importance. Here, by using direct stochastic optical reconstruction microscopy
      coupled to pair correlation analysis (pc-STORM), we were able to visualize and
      measure the size of these clusters. Specifically, we show that they are non
      randomly distributed and have an average size of 67 nm. We also demonstrated that
      polarized MDCK and non-polarized CHO cells have similar cluster distribution and
      size, but different sensitivity to cholesterol depletion. Finally, we derived a
      model that allowed a quantitative characterization of the cluster organization of
      GPI-APs at the apical surface of polarized MDCK cells for the first time.
      Experimental FRET (fluorescence resonance energy transfer)/FLIM (fluorescence
      lifetime imaging microscopy) data were correlated to the theoretical predictions
      of the model.

PMID- 29046392
TI  - Nutlin-3 plus tanshinone IIA exhibits synergetic anti-leukemia effect with
      imatinib by reactivating p53 and inhibiting the AKT/mTOR pathway in Ph+ ALL.
AB  - Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is
      triggered by BCR/ABL kinase. Recent efforts focused on the development of more
      potent tyrosine kinase inhibitors (TKIs) that also inhibit mutant tyrosine
      kinases such as nilotinib and dasatinib. Although major advances in the treatment
      of this aggressive disease with potent inhibitors of the BCR/ABL kinases,
      patients in remission frequently relapse due to drug resistance possibly
      mediated, at least in part, by compensatory activation of growth-signaling
      pathways and protective feedback signaling of leukemia cells in response to TKI
      treatment. Continuous activation of AKT/mTOR signaling and inactivation of p53
      pathway were two mechanisms of TKI resistance. Here, we reported that nutlin-3
      plus tanshinone IIA significantly potentiated the cytotoxic and apoptotic
      induction effects of imatinib by down-regulation of the AKT/mTOR pathway and
      reactivating the p53 pathway deeply in Ph+ ALL cell line. In primary samples from
      Ph+ ALL patients, nutlin-3 plus tanshinone IIA also exhibited synergetic
      cytotoxic effects with imatinib. Of note, three samples from Ph+ ALL patients
      harboring T315I mutation also showed sensitivity to the combined treatment of
      imatinib, nutlin-3 plus tanshinone IIA. In Ph+ ALL mouse models, imatinib
      combined with nutlin-3 plus tanshinone IIA also exhibited synergetic effects on
      reduction in leukemia burden. These results demonstrated that nutlin-3 plus
      tanshinone IIA combined TKI might be a promising treatment strategy for Ph+ ALL
      patients.

PMID- 29046393
TI  - Rac1-stimulated macropinocytosis enhances Gbetagamma activation of PI3Kbeta.
AB  - Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of
      upstream activators, including receptor tyrosine kinases (RTKs), G-protein
      coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families.
      For the Class IA PI 3-kinase PI3Kbeta, two mechanisms for GPCR-mediated
      regulation have been described: direct binding of Gbetagamma subunits to the C2
      helical domain linker of p110beta, and Dock180/Elmo1-mediated activation of Rac1,
      which binds to the Ras-Binding Domain of p110beta. We now show that the
      integration of these dual pathways is unexpectedly complex. In breast cancer
      cells, expression of constitutively activated Rac1 (CA-Rac1) along with either
      GPCR stimulation or expression of Gbetagamma led to an additive PI3Kbeta
      dependent activation of Akt. Whereas CA-Rac1-mediated activation of Akt was
      blocked in cells expressing a mutated PI3Kbeta that cannot bind Gbetagamma,
      Gbetagamma and GPCR-mediated activation of Akt was preserved when Rac1 binding to
      PI3Kbeta was blocked. Surprisingly, PI3Kbeta-dependent CA-Rac1 signaling to Akt
      was still seen in cells expressing a mutant p110beta that cannot bind Rac1.
      Instead of directly binding to PI3Kbeta, CA-Rac1 acts by enhancing Gbetagamma
      coupling to PI3Kbeta, as CA-Rac1-mediated Akt activation was blocked by
      inhibitors of Gbetagamma. Cells expressing CA-Rac1 exhibited a robust induction
      of macropinocytosis, and inhibitors of macropinocytosis blocked the activation of
      Akt by CA-Rac1 or lysophosphatidic acid. Our data suggest that Rac1 can
      potentiate the activation of PI3Kbeta by GPCRs through an indirect mechanism, by
      driving the formation of macropinosomes that serve as signaling platforms for
      Gbetagamma coupling to PI3Kbeta.

PMID- 29046394
TI  - Recombinant human islet amyloid polypeptide forms shorter fibrils and mediates
      beta-cell apoptosis via generation of oxidative stress.
AB  - Protein misfolding and aggregation play an important role in many human diseases
      including Alzheimer's, Parkinson's and type 2 diabetes mellitus (T2DM). The human
      islet amyloid polypeptide (hIAPP) forms amyloid plaques in the pancreas of T2DM
      subjects (>95%) that are involved in deteriorating islet function and in
      mediating beta-cell apoptosis. However, the detailed mechanism of action,
      structure and nature of toxic hIAPP species responsible for this effect remains
      elusive to date mainly due to the high cost associated with the chemical
      synthesis of pure peptide required for these studies. In the present work, we
      attempted to obtain structural and mechanistic insights into the hIAPP
      aggregation process using recombinant hIAPP (rhIAPP) isolated from Escherichia
      coli Results from biophysical and structural studies indicate that the rhIAPP
      self-assembled into highly pure, beta-sheet-rich amyloid fibrils with uniform
      morphology. rhIAPP-mediated apoptosis in INS-1E cells was associated with
      increased oxidative stress and changes in mitochondrial membrane potential. The
      transcript levels of apoptotic genes - Caspase-3 and Bax were found to be up
      regulated, while the levels of the anti-apoptotic gene - Bcl2 were down-regulated
      in rhIAPP-treated cells. Additionally, the expression levels of genes involved in
      combating oxidative stress namely Catalase, SOD1 and GPx were down-regulated.
      rhIAPP exposure also affected glucose-stimulated insulin secretion from isolated
      pancreatic islets. The aggregation of rhIAPP also occurred significantly faster
      when compared with that of the chemically synthesized peptide. We also show that
      the rhIAPP fibrils were shorter and more cytotoxic. In summary, our study is one
      among the few to provide comprehensive evaluation of structural, biophysical and
      cytotoxic properties of rhIAPP.

PMID- 29046395
TI  - Epithelial contribution to the profibrotic stiff microenvironment and
      myofibroblast population in lung fibrosis.
AB  - The contribution of epithelial-to-mesenchymal transition (EMT) to the profibrotic
      stiff microenvironment and myofibroblast accumulation in pulmonary fibrosis
      remains unclear. We examined EMT-competent lung epithelial cells and lung
      fibroblasts from control (fibrosis-free) donors or patients with idiopathic
      pulmonary fibrosis (IPF), which is a very aggressive fibrotic disorder. Cells
      were cultured on profibrotic conditions including stiff substrata and TGF-beta1,
      and analyzed in terms of morphology, stiffness, and expression of
      EMT/myofibroblast markers and fibrillar collagens. All fibroblasts acquired a
      robust myofibroblast phenotype on TGF-beta1 stimulation. Yet IPF myofibroblasts
      exhibited higher stiffness and expression of fibrillar collagens than control
      fibroblasts, concomitantly with enhanced FAKY397 activity. FAK inhibition was
      sufficient to decrease fibroblast stiffness and collagen expression, supporting
      that FAKY397 hyperactivation may underlie the aberrant mechanobiology of IPF
      fibroblasts. In contrast, cells undergoing EMT failed to reach the values
      exhibited by IPF myofibroblasts in all parameters examined. Likewise, EMT could
      be distinguished from nonactivated control fibroblasts, suggesting that EMT does
      not elicit myofibroblast precursors either. Our data suggest that EMT does not
      contribute directly to the myofibroblast population, and may contribute to the
      stiff fibrotic microenvironment through their own stiffness but not their
      collagen expression. Our results also support that targeting FAKY397 may rescue
      normal mechanobiology in IPF.

PMID- 29046396
TI  - Activation of ROCK and MLCK tunes regional stress fiber formation and mechanics
      via preferential myosin light chain phosphorylation.
AB  - The assembly and mechanics of actomyosin stress fibers (SFs) depend on myosin
      regulatory light chain (RLC) phosphorylation, which is driven by myosin light
      chain kinase (MLCK) and Rho-associated kinase (ROCK). Although previous work
      suggests that MLCK and ROCK control distinct pools of cellular SFs, it remains
      unclear how these kinases differ in their regulation of RLC phosphorylation or
      how phosphorylation influences individual SF mechanics. Here, we combine genetic
      approaches with biophysical tools to explore relationships between kinase
      activity, RLC phosphorylation, SF localization, and SF mechanics. We show that
      graded MLCK overexpression increases RLC monophosphorylation (p-RLC) in a graded
      manner and that this p-RLC localizes to peripheral SFs. Conversely, graded ROCK
      overexpression preferentially increases RLC diphosphorylation (pp-RLC), with pp
      RLC localizing to central SFs. Interrogation of single SFs with subcellular laser
      ablation reveals that MLCK and ROCK quantitatively regulate the viscoelastic
      properties of peripheral and central SFs, respectively. The effects of MLCK and
      ROCK on single-SF mechanics may be correspondingly phenocopied by overexpression
      of mono- and diphosphomimetic RLC mutants. Our results point to a model in which
      MLCK and ROCK regulate peripheral and central SF viscoelastic properties through
      mono- and diphosphorylation of RLC, offering new quantitative connections between
      kinase activity, RLC phosphorylation, and SF viscoelasticity.

PMID- 29046397
TI  - Lipid metabolic perturbation is an early-onset phenotype in adult spinster
      mutants: a Drosophila model for lysosomal storage disorders.
AB  - Intracellular accumulation of lipids and swollen dysfunctional lysosomes are
      linked to several neurodegenerative diseases, including lysosomal storage
      disorders (LSD). Detailed characterization of lipid metabolic changes in relation
      to the onset and progression of neurodegeneration is currently missing. We
      systematically analyzed lipid perturbations in spinster (spin) mutants, a
      Drosophila model of LSD-like neurodegeneration. Our results highlight an
      imbalance in brain ceramide and sphingosine in the early stages of
      neurodegeneration, preceding the accumulation of endomembranous structures,
      manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels
      of ceramidase and altering these lipids in spin mutants allowed us to conclude
      that ceramide homeostasis is the driving force in disease progression and is
      integral to spin function in the adult nervous system. We identified 29 novel
      physical interaction partners of Spin and focused on the lipid carrier protein,
      Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within
      organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp
      protein was observed in spin mutant tissues. Finally, increased levels of lipid
      metabolites produced by oenocytes in spin mutants allude to a functional
      interaction between Spin and Lpp, underscoring the systemic nature of lipid
      perturbation in LSD.

PMID- 29046398
TI  - Paxillin regulates cell polarization and anterograde vesicle trafficking during
      cell migration.
AB  - Cell polarization and directed migration play pivotal roles in diverse
      physiological and pathological processes. Herein, we identify new roles for
      paxillin-mediated HDAC6 inhibition in regulating key aspects of cell polarization
      in both two-dimensional and one-dimensional matrix environments. Paxillin, by
      modulating microtubule acetylation through HDAC6 regulation, was shown to control
      centrosome and Golgi reorientation toward the leading edge, a hallmark of cell
      polarization to ensure directed trafficking of promigratory factors. Paxillin was
      also required for pericentrosomal Golgi localization and centrosome cohesion,
      independent of its localization to, and role in, focal adhesion signaling. In
      addition, we provide evidence of an accumulation of paxillin at the centrosome
      that is dependent on focal adhesion kinase (FAK) and identify an important
      collaboration between paxillin and FAK signaling in the modulation of microtubule
      acetylation, as well as centrosome and Golgi organization and polarization.
      Finally, paxillin was also shown to be required for optimal anterograde vesicular
      trafficking to the plasma membrane.

PMID- 29046399
TI  - Dynamic localization of a yeast development-specific PP1 complex during prospore
      membrane formation is dependent on multiple localization signals and complex
      formation.
AB  - During the developmental process of sporulation in Saccharomyces cerevisiae,
      membrane structures called prospore membranes are formed de novo, expand, extend,
      acquire a round shape, and finally become plasma membranes of the spores. GIP1
      encodes a regulatory/targeting subunit of protein phosphatase type 1 that is
      required for sporulation. Gip1 recruits the catalytic subunit Glc7 to septin
      structures that form along the prospore membrane; however, the molecular basis of
      its localization and function is not fully understood. Here we show that Gip1
      changes its localization dynamically and is required for prospore membrane
      extension. Gip1 first associates with the spindle pole body as the prospore
      membrane forms, moves onto the prospore membrane and then to the septins as the
      membrane extends, distributes around the prospore membrane after closure, and
      finally translocates into the nucleus in the maturing spore. Deletion and
      mutation analyses reveal distinct sequences in Gip1 that are required for
      different localizations and for association with Glc7. Binding to Glc7 is also
      required for proper localization. Strikingly, localization to the prospore
      membrane, but not association with septins, is important for Gip1 function.
      Further, our genetic analysis suggests that a Gip1-Glc7 phosphatase complex
      regulates prospore membrane extension in parallel to the previously reported
      Vps13, Spo71, Spo73 pathway.

PMID- 29046401
TI  - Reconstructing the Molecular Function of Genetic Variation in Regulatory
      Networks.
AB  - Over the past decade, genetic studies have recognized hundreds of polymorphic DNA
      loci called response QTLs (reQTLs) as potential contributors to interindividual
      variation in transcriptional responses to stimulations. Such reQTLs commonly
      affect the transduction of signals along the regulatory network that controls
      gene transcription. Identifying the pathways through which reQTLs perturb the
      underlying network has been a major challenge. Here, we present GEVIN ("Genome
      wide Embedding of Variation In Networks"), a methodology that simultaneously
      identifies a reQTL and the particular pathway in which the reQTL affects
      downstream signal transduction along the network. Using synthetic data, we show
      that this algorithm outperforms existing pathway identification and reQTL
      identification methods. We applied GEVIN to the analysis of murine and human
      dendritic cells in response to pathogenic components. These analyses revealed
      significant reQTLs together with their perturbed Toll-like receptor signaling
      pathways. GEVIN thus offers a powerful framework that renders a comprehensive
      picture of disease-related DNA loci and their molecular functions within
      regulatory networks.

PMID- 29046400
TI  - Ribosome Biogenesis Modulates Ty1 Copy Number Control in Saccharomyces
      cerevisiae.
AB  - Transposons can impact the host genome by altering gene expression and
      participating in chromosome rearrangements. Therefore, organisms evolved
      different ways to minimize the level of transposition. In Saccharomyces
      cerevisiae and its close relative S. paradoxus, Ty1 copy number control (CNC) is
      mediated by the self-encoded restriction factor p22, which is derived from the
      GAG capsid gene and inhibits virus-like particle (VLP) assembly and function.
      Based on secondary screens of Ty1 cofactors, we identified LOC1, a RNA
      localization/ribosome biogenesis gene that affects Ty1 mobility predominantly in
      strains harboring Ty1 elements. Ribosomal protein mutants rps0bDelta and
      rpl7aDelta displayed similar CNC-specific phenotypes as loc1Delta, suggesting
      that ribosome biogenesis is critical for CNC. The level of Ty1 mRNA and Ty1
      internal (Ty1i) transcripts encoding p22 was altered in these mutants, and
      displayed a trend where the level of Ty1i RNA increased relative to full-length
      Ty1 mRNA. The level of p22 increased in these mutants, and the half-life of p22
      also increased in a loc1Delta mutant. Transcriptomic analyses revealed small
      changes in the level of Ty1 transcripts or efficiency of translation initiation
      in a loc1Delta mutant. Importantly, a loc1Delta mutant had defects in assembly of
      Gag complexes and packaging Ty1 RNA. Our results indicate that defective ribosome
      biogenesis enhances CNC by increasing the level of p22, and raise the possibility
      for versatile links between VLP assembly, its cytoplasmic environment, and a
      novel stress response.

PMID- 29046404
TI  - Cranberry Reduces the Risk of Urinary Tract Infection Recurrence in Otherwise
      Healthy Women: A Systematic Review and Meta-Analysis.
AB  - Background: Cranberry (Vaccinium spp.) has been advocated for treatment of
      urinary tract infection (UTI); however, its efficacy is controversial. Women have
      a 50% risk of UTI over their lifetime, and ~20-30% experience a subsequent UTI
      recurrence.Objective: We conducted this meta-analysis to assess the effect of
      cranberry on the risk of UTI recurrence in otherwise healthy women.Methods:
      Literature published before January 2011 was obtained from 2 published systematic
      reviews, and we conducted updated searches in EMBASE and MEDLINE (through July
      2017). We included randomized controlled trials that were conducted in generally
      healthy nonpregnant women aged >=18 y with a history of UTI, compared cranberry
      intervention to a placebo or control, and reported the outcome as the number of
      participants experiencing a UTI. Two researchers conducted abstract and full-text
      screenings, data extractions, and risk of bias assessments independently, and
      discrepancies were resolved by group consensus. Meta-analyses were performed by
      using Stata SE software (version 13). We employed a fixed-effect model using the
      Mantel-Haenszel method to estimate the summary risk if the heterogeneity was low
      to moderate (I2 < 50%). Otherwise, we applied a random-effects model using the
      DerSimonian-Laird method.Results: We identified 7 randomized controlled trials
      conducted in healthy women at risk of UTI (n = 1498 participants). Results of the
      meta-analysis showed that cranberry reduced the risk of UTI by 26% (pooled risk
      ratio: 0.74; 95% CI: 0.55, 0.98; I2 = 54%). Risk of bias indicated that 2 studies
      had high loss to follow-up or selective outcome reporting. Overall, the studies
      were relatively small, with only 2 having >300 participants.Conclusion: These
      results suggest that cranberry may be effective in preventing UTI recurrence in
      generally healthy women; however, larger high-quality studies are needed to
      confirm these findings. This trial was registered at crd.york.ac.uk/prospero as
      CRD42015024439.

PMID- 29046402
TI  - The Hybrid Incompatibility Genes Lhr and Hmr Are Required for Sister Chromatid
      Detachment During Anaphase but Not for Centromere Function.
AB  - Crosses between Drosophila melanogaster females and Drosophila simulans males
      produce hybrid sons that die at the larval stage. This hybrid lethality is
      suppressed by loss-of-function mutations in the D. melanogaster Hybrid male
      rescue (Hmr) or in the D. simulans Lethal hybrid rescue (Lhr) genes. Previous
      studies have shown that Hmr and Lhr interact with heterochromatin proteins and
      suppress expression of transposable elements within D. melanogaster It also has
      been proposed that Hmr and Lhr function at the centromere. We examined mitotic
      divisions in larval brains from Hmr and Lhr single mutants and Hmr; Lhr double
      mutants in D. melanogaster In none of the mutants did we observe defects in
      metaphase chromosome alignment or hyperploid cells, which are hallmarks of
      centromere or kinetochore dysfunction. In addition, we found that Hmr-HA and Lhr
      HA do not colocalize with centromeres either during interphase or mitotic
      division. However, all mutants displayed anaphase bridges and chromosome
      aberrations resulting from the breakage of these bridges, predominantly at the
      euchromatin-heterochromatin junction. The few dividing cells present in hybrid
      males showed fuzzy and irregularly condensed chromosomes with unresolved sister
      chromatids. Despite this defect in condensation, chromosomes in hybrids managed
      to align on the metaphase plate and undergo anaphase. We conclude that there is
      no evidence for a centromeric function of Hmr and Lhr within D. melanogaster nor
      for a centromere defect causing hybrid lethality. Instead, we find that Hmr and
      Lhr are required in D. melanogaster for detachment of sister chromatids during
      anaphase.

PMID- 29046403
TI  - Distinguishing Among Modes of Convergent Adaptation Using Population Genomic
      Data.
AB  - Geographically separated populations can convergently adapt to the same selection
      pressure. Convergent evolution at the level of a gene may arise via three
      distinct modes. The selected alleles can (1) have multiple independent mutational
      origins, (2) be shared due to shared ancestral standing variation, or (3) spread
      throughout subpopulations via gene flow. We present a model-based, statistical
      approach that utilizes genomic data to detect cases of convergent adaptation at
      the genetic level, identify the loci involved and distinguish among these modes.
      To understand the impact of convergent positive selection on neutral diversity at
      linked loci, we make use of the fact that hitchhiking can be modeled as an
      increase in the variance in neutral allele frequencies around a selected site
      within a population. We build on coalescent theory to show how shared hitchhiking
      events between subpopulations act to increase covariance in allele frequencies
      between subpopulations at loci near the selected site, and extend this theory
      under different models of migration and selection on the same standing variation.
      We incorporate this hitchhiking effect into a multivariate normal model of allele
      frequencies that also accounts for population structure. Based on this theory, we
      present a composite-likelihood-based approach that utilizes genomic data to
      identify loci involved in convergence, and distinguishes among alternate modes of
      convergent adaptation. We illustrate our method on genome-wide polymorphism data
      from two distinct cases of convergent adaptation. First, we investigate the
      adaptation for copper toxicity tolerance in two populations of the common yellow
      monkey flower, Mimulus guttatus We show that selection has occurred on an allele
      that has been standing in these populations prior to the onset of copper mining
      in this region. Lastly, we apply our method to data from four populations of the
      killifish, Fundulus heteroclitus, that show very rapid convergent adaptation for
      tolerance to industrial pollutants. Here, we identify a single locus at which
      both independent mutation events and selection on an allele shared via gene flow,
      either slightly before or during selection, play a role in adaptation across the
      species' range.

PMID- 29046405
TI  - Potato Consumption Does Not Increase Blood Pressure or Incident Hypertension in 2
      Cohorts of Spanish Adults.
AB  - Background: Potatoes have a high glycemic load but also antioxidants, vitamins,
      and minerals. It is unclear what mechanisms are involved in relation to their
      effect on blood pressure (BP) and hypertension.Objectives: This study aimed to
      assess the association between potato consumption, BP changes, and the risk of
      hypertension in 2 Spanish populations.Methods: Separate analyses were performed
      in PREDIMED (PREvencion con DIeta MEDiterranea), a multicenter nutrition
      intervention trial of adults aged 55-80 y, and the SUN (Seguimiento Universidad
      de Navarra) project, a prospective cohort made up of university graduates and
      educated adults with ages (means +/- SDs) of 42.7 +/- 13.3 y for men and 35.1 +/-
      10.7 y for women. In PREDIMED, generalized estimating equations adjusted for
      lifestyle and dietary characteristics were used to assess changes in BP across
      quintiles of total potato consumption during a 4-y follow-up. Controlled BP
      values (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) during follow-up were
      also assessed. For SUN, multivariate-adjusted HRs for incident hypertension
      during a mean 6.7-y follow-up were calculated.Results: In PREDIMED, the total
      potato intake was 81.9 +/- 40.6 g/d. No overall differences in systolic or
      diastolic BP changes were detected based on consumption of potatoes. For total
      potatoes, the mean difference in change between quintile 5 (highest intake) and
      quintile 1 (lowest intake) in systolic BP after multivariate adjustment was -0.90
      mm Hg (95% CI: -2.56, 0.76 mm Hg; P-trend = 0.1) and for diastolic BP was -0.02
      mm Hg (95% CI: -0.93, 0.89 mm Hg; P-trend = 0.8). In SUN, the total potato
      consumption was 52.7 +/- 33.6 g/d, and no significant association between potato
      consumption and hypertension incidence was observed in the fully adjusted HR for
      total potato consumption (quintile 5 compared with quintile 1: 0.98; 95% CI:
      0.80, 1.19; P-trend = 0.8).Conclusions: Potato consumption is not associated with
      changes over 4 y in blood pressure among older adults in Spain or with the risk
      of hypertension among Spanish adults. This trial was registered at www.controlled
      trials.com as ISRCTN35739639.

PMID- 29046406
TI  - Cold Extrusion but Not Coating Affects Iron Bioavailability from Fortified Rice
      in Young Women and Is Associated with Modifications in Starch Microstructure and
      Mineral Retention during Cooking.
AB  - Background: Rice can be fortified with the use of hot or cold extrusion or
      coating, but the nutritional qualities of the resulting rice grains have never
      been directly compared.Objective: Using fortified rice produced by coating or hot
      or cold extrusion, we compared 1) iron and zinc absorption with the use of stable
      isotopes, 2) iron and zinc retention during cooking, and 3) starch
      microstructure.Methods: We conducted 2 studies in young women: in study 1 [n =
      19; mean +/- SD age: 26.2 +/- 3.4 y; body mass index (BMI; in kg/m2): 21.3 +/-
      1.6], we compared the fractional iron absorption (FAFe) from rice meals
      containing isotopically labeled ferric prophosphate (57FePP), zinc oxide (ZnO),
      citric acid, and micronutrients fortified through hot extrusion (HER1) with rice
      meals fortified through cold extrusion containing 57FePP, ZnO, citric acid, and
      micronutrients (CER); in study 2 (n = 22; age: 24 +/- 4 y; BMI: 21.2 +/- 1.3), we
      compared FAFe and fractional zinc absorption (FAZn) from rice meals fortified
      through hot extrusion (HER2) compared with rice meals fortified through coating
      containing 57FePP, ZnO, a citric acid and trisodium cirate mixture (CA/TSC), and
      micronutrients (COR) relative to rice meals extrinsically fortified with ferrous
      sulfate (reference). Rice types HER1 and CER contained citric acid, whereas types
      HER2 and COR contained CA/TSC. We assessed retention during standardized cooking
      experiments and characterized the rice starch microstructure.Results: FAFe (95%
      CI) was greater from CER [2.2% (1.4%, 3.4%)] than from HER1 [1.2% (0.7%, 2.0%)]
      (P = 0.036). There was no difference in FAFe between HER2 [5.1% (3.7%, 7.1%)] and
      COR [4.0% (2.9%, 5.4%)] (P = 0.14), but FAFe from COR was lower than that from
      the reference meal [6.6% (4.9%, 9.0%)] (P = 0.003), and the geometric mean FAZn
      (95% CI) did not differ between HER2 [9.5% (7.9%, 11.6%)] and COR [9.6% (8.7%,
      10.7%)] (P = 0.92). Cooking in a rice-to-water ratio of 1:2 resulted in iron and
      zinc retentions >80%, and cooking in excess water did not affect iron retention
      from hot-extruded rice but caused iron losses of 25% from CER and COR. Distinct
      variations in starch microstructure were found in CER and HER1.Conclusions: Iron
      absorption was 64% higher from CER than from hot-extruded rice, with no
      difference between COR compared with hot-extruded rice. Lower extrusion
      temperatures may generate a more readily digestible starch structure, allowing
      for greater iron release in vivo but lower mineral retention during cooking. This
      trial was registered at clinicaltrials.gov as NCT02176759.

PMID- 29046407
TI  - An Improved Extended-Spectrum-beta-Lactamase Detection Test Utilizing Aztreonam
      plus Clavulanate.
AB  - Clinical laboratories test for extended-spectrum beta-lactamases (ESBLs) for
      epidemiological and infection control purposes and also for the potential of
      cephalosporins to cause therapeutic failures. Testing can be problematic, because
      the CLSI does not recommend the testing of all producers of ESBLs and also
      falsely negative results may occur with isolates that coproduce AmpC. Boronic
      acid-supplemented tests can enhance ESBL detection in AmpC producers. Because
      aztreonam inhibits AmpCs, a study was designed to compare ESBL detection by the
      CLSI disk test (CLSI), a boronic acid-supplemented CLSI disk test (CLSI plus BA),
      and an aztreonam plus clavulanate disk test (ATM plus CA). The study tested 100
      well-characterized Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas
      aeruginosa isolates. Seventy produced TEM, SHV, or CTX-M ESBLs, with 15
      coproducing an AmpC and 11 coproducing a metallo-beta-lactamase. Thirty ESBL
      negative isolates were also tested. Tests were inoculated by CLSI methodology and
      interpreted as positive if an inhibitor caused a zone diameter increase of >=5
      mm. The percentages of ESBL producers detected were as follows: ATM plus CA,
      95.7%; CLSI plus BA, 88.6%; and CLSI, 78.6%. When AmpC was coproduced, the
      sensitivities of the tests were as follows: ATM plus CA, 100%; CLSI plus BA,
      93.3%; and CLSI, 60%. ATM plus CA also detected an ESBL in 90.1% of isolates that
      coproduced a metallo-beta-lactamase. Falsely positive tests occurred only with
      the CLSI and CLSI plus BA tests. Overall, the ATM plus CA test detected ESBLs
      more accurately than the CLSI and CLSI plus BA tests, especially with isolates
      coproducing an AmpC or metallo-beta-lactamase.

PMID- 29046408
TI  - "Smart Diagnosis" of Parasitic Diseases by Use of Smartphones.
AB  - Accurate and rapid diagnosis is crucial in combating parasitic diseases that
      cause millions of deaths worldwide. However, the scarcity of specialized
      diagnostic equipment in low- and middle-income countries is one of the barriers
      to effective management of parasitic diseases and warrants the need for
      alternative, inexpensive, point-of-care diagnostic tools. Due to their multiple
      built-in sensors, smartphones offer cost-effective alternative to expensive
      diagnostic devices. However, the use of smartphones in parasitic diagnoses
      remains in its infancy. This minireview describes various smartphone-based
      devices applied specifically for the diagnosis of parasitic diseases and
      discusses challenges and potential implications for their use in future.

PMID- 29046409
TI  - Using Treponemal Assay Signal Strength Cutoff Ratios To Predict Syphilis
      Infection.
AB  - Syphilis screening with the reverse algorithm, a treponemal test for screening
      followed by a nontreponemal test if reactive, is increasingly being used. That
      algorithm has several advantages, including use of an automated screening test,
      saving on laboratory time and costs, as well as detection of very early syphilis
      infection. However, under that algorithm, in situations where the treponemal
      result is positive and the nontreponemal result is nonreactive a second
      treponemal test must be performed, which may actually lead to inefficiencies in
      the laboratory. In this issue of the Journal of Clinical Microbiology, Y. F.
      Fakile et al. (J Clin Microbiol 56:e01165-17, 2017,
      https://doi.org/10.1128/JCM.01165-17) report the results of their study, which
      demonstrates the capability of signal strength ratio cutoffs for automated
      treponemal immunoassays to predict the outcome of repeat treponemal testing.
      Their findings suggest that anti-treponemal signal strength ratio values above a
      cutoff value can be used in lieu of repeat treponemal tests.

PMID- 29046410
TI  - Correlation of Treponemal Immunoassay Signal Strength Values with Reactivity of
      Confirmatory Treponemal Testing.
AB  - Automated treponemal immunoassays are used for syphilis screening with the
      reverse-sequence algorithm; discordant results (e.g., enzyme immunoassay [EIA]
      reactive and reactive plasma reagin [RPR] nonreactive) are resolved with a second
      treponemal test. We conducted a study to determine automated immunoassay signal
      strength values consistently correlating with reactive confirmatory treponemal
      testing. We conducted a cross-sectional analysis of four automated immunoassays
      (BioPlex 2200 microbead immunoassay [MBIA], Liaison chemiluminescence immunoassay
      [CIA], Advia-Centaur CIA, and Trep-Sure EIA) and three manual assays (Treponema
      pallidum particle agglutination [TP-PA], fluorescent treponemal antibody
      absorption [FTA-ABS] test, and Inno-LIA line immunoassay). We compared signal
      strength values of automated immunoassays and positive and negative agreement.
      Among 1,995 specimens, 908 (45.5%) were true positives (>=4/7 tests reactive) and
      1,087 (54.5%) were true negatives (>=4/7 tests nonreactive). Positive agreement
      ranged from 86.1% (83.7 to 88.2%) for FTA-ABS to 99.7% (99.0 to 99.9%) for Advia
      Centaur CIA; negative agreement ranged from 86.3% (84.1 to 88.2%) for Trep-Sure
      EIA to 100% for TP-PA (99.6 to 100%). Increasing signal strength values
      correlated with increasing reactivity of confirmatory testing (P < 0.0001 for all
      automated immunoassays by Cochran-Armitage test for trend). All automated
      immunoassays had signal strength cutoffs corresponding to >=4/7 reactive
      treponemal tests. BioPlex MBIA and Liaison CIA had signal strength cutoffs
      correlating with >=99% and 100% TP-PA reactivity, respectively. The Advia-Centaur
      CIA and Trep-Sure EIA had signal strength cutoffs correlating with at least 95%
      TP-PA reactivity. All automated immunoassays had signal strength cutoffs
      correlating with at least 95% FTA-ABS reactivity. Assuming that a 95% level of
      confirmation is adequate, these signal strength values can be used in lieu of
      confirmatory testing with TP-PA and FTA-ABS.

PMID- 29046411
TI  - Rapid Detection and Differentiation of Clinically Relevant Candida Species
      Simultaneously from Blood Culture by Use of a Novel Signal Amplification
      Approach.
AB  - Fungal bloodstream infections are a significant problem in the United States,
      with an attributable mortality rate of up to 40%. An early diagnosis to direct
      appropriate therapy has been shown to be critical to reduce mortality rates.
      Conventional phenotypic methods for fungal detection take several days, which is
      often too late to impact outcomes. Herein, we describe a cost-effective multiplex
      assay platform for the rapid detection and differentiation of major clinically
      relevant Candida species directly from blood culture. This approach utilizes a
      novel biotin-labeled polymer-mediated signal amplification process combined with
      targeting rRNA to exploit phylogenetic differences for sensitive and unambiguous
      species identification; this assay detects seven pathogenic Candida species (C.
      albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. lusitaniae,
      and C. guilliermondii) simultaneously with very high specificity to the species
      level in less than 80 min with the limits of detection at 1 * 103 to 10 * 103
      CFU/ml or as few as 50 CFU per assay. The performance of the described assay was
      verified with 67 clinical samples (including mixed multiple-species infections as
      well), with an overall 100% agreement with matrix-assisted laser desorption
      ionization (MALDI) mass spectrometry-based reference results. By providing a
      species identity rapidly, the clinician is aided with information that may direct
      appropriate therapy sooner and more accurately than current approaches, including
      PCR-based tests.

PMID- 29046412
TI  - Detection of Plasmodium Species by High-Resolution Melt Analysis of DNA from
      Blood Smears Acquired in Southwestern Uganda.
AB  - Microscopic diagnosis of malaria using Giemsa-stained blood smears is the
      standard of care in resource-limited settings. These smears represent a potential
      source of DNA for PCR testing to confirm Plasmodium infections or for
      epidemiological studies of archived samples. Therefore, we assessed the use of
      DNA extracts from stained blood smears for the detection of Plasmodium species
      using real-time PCR. We extracted DNA from archived blood smears and
      corresponding red blood cell pellets collected from asymptomatic children in
      southwestern Uganda in 2010. We then performed real-time PCR followed by high
      resolution melting (HRM) to identify Plasmodium species, and we compared our
      results to those of microscopy. We analyzed a total of 367 blood smears and
      corresponding red blood cell pellets, including 185 smears (50.4%) that were
      positive by microscopy. Compared to microscopy, PCR-HRM analysis of smear DNA had
      a sensitivity of 93.0% (95% confidence interval [CI], 88.2 to 96.2%) and a
      specificity of 96.7% (95% CI, 93.0 to 98.8%), and PCR-HRM analysis of pellet DNA
      had a sensitivity of 100.0% (95% CI, 98.0 to 100.0%) and a specificity of 94.0%
      (95% CI, 89.4 to 96.9%). Identification of positive PCR-HRM results to the
      species level revealed Plasmodium falciparum (92.0%), Plasmodium ovale (5.6%),
      and Plasmodium malariae (2.4%). PCR-HRM analysis of DNA extracts from Giemsa
      stained thick blood smears or corresponding blood pellets had high sensitivity
      and specificity for malaria diagnosis, compared to microscopy. Therefore, blood
      smears can provide an adequate source of DNA for confirmation of Plasmodium
      species infections and can be used for retrospective genetic studies.

PMID- 29046414
TI  - Early-career researchers: an interview with Jodie Rummer.
AB  - Jodie Rummer is an Associate Professor at James Cook University, Australia, where
      she specialises in conservation physiology. She received her Bachelor's degree in
      Marine Biology and her Master's degree from the University of West Florida, USA.
      Rummer then moved to the University of British Columbia, Canada, for her PhD in
      Zoology with Colin Brauner, after which she completed a short postdoc with Dave
      Randall at the City University of Hong Kong. She has been recognised with a
      L'Oreal-UNESCO For Women in Science Fellowship and was one of the Australia
      Broadcasting Corporation's Top Five Scientists under 40 in 2016.

PMID- 29046413
TI  - Prediction of Local Transmission of Mycobacterium tuberculosis Isolates of a
      Predominantly Beijing Lineage by Use of a Variable-Number Tandem-Repeat Typing
      Method Incorporating a Consensus Set of Hypervariable Loci.
AB  - Strain genotyping based on the variable-number tandem repeat (VNTR) is widely
      applied for identifying the transmission of Mycobacterium tuberculosis A
      consensus set of four hypervariable loci (1982, 3232, 3820, and 4120) has been
      proposed to improve the discrimination of Beijing lineage strains. Herein, we
      evaluated the utility of these four hypervariable loci for tracing local
      tuberculosis transmission in 981 cases over a 14-month period in Japan (2010 to
      2011). We used six different VNTR systems, with or without the four hypervariable
      loci. Patient ages and weighted standard distances (a measure of the dispersion
      of genotype-clustered cases) were used as proxies for estimating local
      tuberculosis transmission. The highest levels of isolate discrimination were
      achieved with VNTR systems that incorporated the four hypervariable loci (i.e.,
      the Japan Anti-Tuberculosis Association [JATA]18-VNTR, mycobacterial interspersed
      repetitive unit [MIRU]28-VNTR, and 24Beijing-VNTR). The clustering rates by
      JATA12-VNTR, MIRU15-VNTR, JATA15-VNTR, JATA18-VNTR, MIRU28-VNTR, and 24Beijing
      VNTR systems were 52.2%, 51.0%, 39.0%, 24.1%, 23.1%, and 22.0%, respectively. As
      the discriminative power increased, the median weighted standard distances of the
      clusters tended to decrease (from 311 to 80 km, P < 0.001, Jonckheere-Terpstra
      trend test). Concurrently, the median ages of patients in the clusters tended to
      decrease (from 68 to 60 years, P < 0.001, Jonckheere-Terpstra trend test). These
      findings suggest that strain typing using the four hypervariable loci improves
      the prediction of active local tuberculosis transmission. The four-locus set can
      therefore contribute to the targeted control of tuberculosis in settings with
      high prevalence of Beijing lineage strains.

PMID- 29046415
TI  - Skeletal stiffening in an amphibious fish out of water is a response to increased
      body weight.
AB  - Terrestrial animals must support their bodies against gravity, while aquatic
      animals are effectively weightless because of buoyant support from water. Given
      this evolutionary history of minimal gravitational loading of fishes in water, it
      has been hypothesized that weight-responsive musculoskeletal systems evolved
      during the tetrapod invasion of land and are thus absent in fishes. Amphibious
      fishes, however, experience increased effective weight when out of water - are
      these fishes responsive to gravitational loading? Contrary to the tetrapod-origin
      hypothesis, we found that terrestrial acclimation reversibly increased gill arch
      stiffness (~60% increase) in the amphibious fish Kryptolebias marmoratus when
      loaded normally by gravity, but not under simulated microgravity. Quantitative
      proteomics analysis revealed that this change in mechanical properties occurred
      via increased abundance of proteins responsible for bone mineralization in other
      fishes as well as in tetrapods. Type X collagen, associated with endochondral
      bone growth, increased in abundance almost ninefold after terrestrial
      acclimation. Collagen isoforms known to promote extracellular matrix cross
      linking and cause tissue stiffening, such as types IX and XII collagen, also
      increased in abundance. Finally, more densely packed collagen fibrils in both
      gill arches and filaments were observed microscopically in terrestrially
      acclimated fish. Our results demonstrate that the mechanical properties of the
      fish musculoskeletal system can be fine-tuned in response to changes in effective
      body weight using biochemical pathways similar to those in mammals, suggesting
      that weight sensing is an ancestral vertebrate trait rather than a tetrapod
      innovation.

PMID- 29046416
TI  - It's just sand between the toes: how particle size and shape variation affect
      running performance and kinematics in a generalist lizard.
AB  - Animals must cope with and be able to move effectively on a variety of
      substrates. Substrates composed of granular media, such as sand and gravel, are
      extremely common in nature, and vary tremendously in particle size and shape.
      Despite many studies of the properties of granular media and comparisons of
      locomotion between granular and solid substrates, the effects of systematically
      manipulating these media on locomotion is poorly understood. We studied granular
      media ranging over four orders of magnitude in particle size, and differing in
      the amount of particle shape variation, to determine how these factors affected
      substrate physical properties and sprinting in the generalist lizard Eremias
      arguta We found that media with intermediate particle sizes had high bulk
      densities, low angles of stability and low load-bearing capacities. Rock
      substrates with high shape variation had higher values for all three properties
      than glass bead substrates with low shape variation. We found that E. arguta had
      the highest maximum velocities and accelerations on intermediate size particles,
      and higher velocities on rock than glass beads. Lizards had higher stride
      frequencies and lower duty factors on intermediate particle size substrates, but
      their stride lengths did not change with substrate. Our findings suggest that
      sand and gravel may represent different locomotor challenges for animals. Sand
      substrates provide animals with an even surface for running, but particles shift
      underfoot. In contrast, gravel particles are heavy, so move far less underfoot,
      yet provide the animal with an uneven substrate.

PMID- 29046417
TI  - Life history adjustments to intestinal inflammation in a gut nematode.
AB  - Many parasitic nematodes establish chronic infections. This implies a finely
      tuned interaction with the host immune response in order to avoid infection
      clearance. Although a number of immune interference mechanisms have been
      described in nematodes, how parasites adapt to the immune environment provided by
      their hosts remains largely unexplored. Here, we used the gastrointestinal
      nematode Heligmosomoides polygyrus to investigate the plasticity of life history
      traits and immunomodulatory mechanisms in response to intestinal inflammation. We
      adopted an experimental model of induced colitis and exposed worms to intestinal
      inflammation at two different developmental stages (larvae and adults). We found
      that H. polygyrus responded to intestinal inflammation by up-regulating the
      expression of a candidate gene involved in the interference with the host immune
      response. Worms infecting mice with colitis also had better infectivity (earlier
      adult emergence in the intestinal lumen and higher survival) compared with worms
      infecting control hosts, suggesting that H. polygyrus adjusted its life history
      schedule in response to intestinal inflammation.

PMID- 29046418
TI  - Escaping blood-fed malaria mosquitoes minimize tactile detection without
      compromising on take-off speed.
AB  - To escape after taking a blood meal, a mosquito must exert forces sufficiently
      high to take off when carrying a load roughly equal to its body weight, while
      simultaneously avoiding detection by minimizing tactile signals exerted on the
      host's skin. We studied this trade-off between escape speed and stealth in the
      malaria mosquito Anopheles coluzzii using 3D motion analysis of high-speed
      stereoscopic videos of mosquito take-offs and aerodynamic modeling. We found that
      during the push-off phase, mosquitoes enhanced take-off speed using aerodynamic
      forces generated by the beating wings in addition to leg-based push-off forces,
      whereby wing forces contributed 61% of the total push-off force. Exchanging leg
      derived push-off forces for wing-derived aerodynamic forces allows the animal to
      reduce peak force production on the host's skin. By slowly extending their long
      legs throughout the push-off, mosquitoes spread push-off forces over a longer
      time window than insects with short legs, thereby further reducing peak leg
      forces. Using this specialized take-off behavior, mosquitoes are capable of
      reaching take-off speeds comparable to those of similarly sized fruit flies, but
      with weight-normalized peak leg forces that were only 27% of those of the fruit
      flies. By limiting peak leg forces, mosquitoes possibly reduce the chance of
      being detected by the host. The resulting combination of high take-off speed and
      low tactile signals on the host might help increase the mosquito's success in
      escaping from blood-hosts, which consequently also increases the chance of
      transmitting vector-borne diseases, such as malaria, to future hosts.

PMID- 29046419
TI  - High diving metabolic rate indicated by high-speed transit to depth in negatively
      buoyant long-finned pilot whales.
AB  - To maximize foraging duration at depth, diving mammals are expected to use the
      lowest cost optimal speed during descent and ascent transit and to minimize the
      cost of transport by achieving neutral buoyancy. Here, we outfitted 18 deep
      diving long-finned pilot whales with multi-sensor data loggers and found
      indications that their diving strategy is associated with higher costs than those
      of other deep-diving toothed whales. Theoretical models predict that optimal
      speed is proportional to (basal metabolic rate/drag)1/3 and therefore to body
      mass0.05 The transit speed of tagged animals (2.7+/-0.3 m s-1) was substantially
      higher than the optimal speed predicted from body mass (1.4-1.7 m s-1). According
      to the theoretical models, this choice of high transit speed, given a similar
      drag coefficient (median, 0.0035) to that in other cetaceans, indicated greater
      basal metabolic costs during diving than for other cetaceans. This could explain
      the comparatively short duration (8.9+/-1.5 min) of their deep dives (maximum
      depth, 444+/-85 m). Hydrodynamic gliding models indicated negative buoyancy of
      tissue body density (1038.8+/-1.6 kg m-3, +/-95% credible interval, CI) and
      similar diving gas volume (34.6+/-0.6 ml kg-1, +/-95% CI) to those in other deep
      diving toothed whales. High diving metabolic rate and costly negative buoyancy
      imply a 'spend more, gain more' strategy of long-finned pilot whales, differing
      from that in other deep-diving toothed whales, which limits the costs of
      locomotion during foraging. We also found that net buoyancy affected the optimal
      speed: high transit speeds gradually decreased during ascent as the whales
      approached neutral buoyancy owing to gas expansion.

PMID- 29046420
TI  - DELLA1-Mediated Gibberellin Signaling Regulates Cytokinin-Dependent Symbiotic
      Nodulation.
AB  - In legume plants, low-nitrogen soils promote symbiotic interactions with
      rhizobial bacteria, leading to the formation of nitrogen-fixing root nodules.
      Among critical signals regulating this developmental process are bacterial Nod
      Factors (NFs) and several plant hormones, including cytokinins (CKs) and
      gibberellins (GAs). Here, we show in Medicago truncatula that GA signaling
      mediated by DELLA1 decreases the amount of bioactive CKs in roots and negatively
      impacts the Cytokinin Response1 (CRE1)-dependent NF activation of a subset of CK
      signaling genes as well as of the CK-regulated Nodulation Signaling Pathway2 and
      Ethylene Response Factor Required for Nodulation1 early nodulation genes.
      Consistently, a dominant-active DELLA1 protein can partially rescue the reduced
      nodulation of the cre1 mutant and triggers the formation of nodule-like
      structures when expressed in the root cortex or in the root epidermis. This
      suggests a model where the DELLA1-mediated GA signaling interplays with the CRE1
      dependent CK pathway to regulate early nodulation in response to both NF and CK
      signals critical for this symbiotic interaction.

PMID- 29046422
TI  - The fate of nonselected activity in saccadic decisions: distinct goal-related and
      history-related modulation.
AB  - The global effect (GE) traditionally refers to the tendency of effectors (e.g.,
      hand, eyes) to first land in between two nearby stimuli, forming a unimodal
      distribution. By measuring a shift of this distribution, recent studies used the
      GE to assess the presence of decision-related inputs on the motor map for eye
      movements. However, this method cannot distinguish whether one stimulus is
      inhibited or the other is facilitated and could not detect situations where both
      stimuli are inhibited or facilitated. Here, we detect deviations in the bimodal
      distribution of landing positions for remote stimuli and find that this bimodal
      GE reveals the presence, location, and polarity (facilitation or inhibition) of
      history-related and goal-related modulation of the nonselected activity (e.g.,
      the distractor activity in correct trials, and the target activity in error
      trials). We tested, for different interstimulus distances, the effect of the
      rarity of double-stimulus trials and the difference between performing a
      discrimination task compared with free choice. Our work shows that the effect of
      rarity is symmetric and decreases with interstimulus distances, while the effect
      of goal-directed discrimination is asymmetric - occurring only when the
      distractor is selected for the saccade - and maintained across interstimulus
      distances. These results suggest that the former effect changes the response
      property of the motor map, while the latter specifically facilitates the target
      location. NEW & NOTEWORTHY Deviations in landing positions for saccades to
      targets and distractors reveal the presence, location and polarity of history
      related or goal-related signals. Goal-directed discrimination appears to
      facilitate the target location, rather than inhibiting the distractor location,
      Rare occurrence of a choice appears to indiscriminately increase the neural
      response for both locations.

PMID- 29046423
TI  - Intrinsic physiology of inhibitory neurons changes over auditory development.
AB  - During auditory development, changes in membrane properties promote the ability
      of excitatory neurons in the brain stem to code aspects of sound, including the
      level and timing of a stimulus. Some of these changes coincide with hearing
      onset, suggesting that sound-driven neural activity produces developmental
      plasticity of ion channel expression. While it is known that the coding
      properties of excitatory neurons are modulated by inhibition in the mature
      system, it is unknown whether there are also developmental changes in the
      membrane properties of brain stem inhibitory neurons. We investigated the primary
      source of inhibition in the avian auditory brain stem, the superior olivary
      nucleus (SON). The present studies test the hypothesis that, as in excitatory
      neurons, the membrane properties of these inhibitory neurons change after hearing
      onset. We examined SON neurons at different stages of auditory development:
      embryonic days 14-16 (E14-E16), a time at which cochlear ganglion neurons are
      just beginning to respond to sound; later embryonic stages (E18-E19); and after
      hatching (P0-P2). We used in vitro whole cell patch electrophysiology to explore
      physiological changes in SON. Age-related changes were observed at the level of a
      single spike and in multispiking behavior. In particular, tonic behavior,
      measured as a neuron's ability to sustain tonic firing over a range of current
      steps, became more common later in development. Voltage-clamp recordings and
      biophysical models were employed to examine how age-related increases in ion
      currents enhance excitability in SON. Our findings suggest that concurrent
      increases in sodium and potassium currents underlie the emergence of tonic
      behavior. NEW & NOTEWORTHY This article is the first to examine heterogeneity of
      neuronal physiology in the inhibitory nucleus of the avian auditory system and
      demonstrate that tonic firing here emerges over development. By pairing computer
      simulations with physiological data, we show that increases in both sodium and
      potassium channels over development are necessary for the emergence of tonic
      firing.

PMID- 29046421
TI  - Fluctuating Light Takes Crop Photosynthesis on a Rollercoaster Ride.

PMID- 29046424
TI  - Passive sensorimotor stimulation triggers long lasting alpha-band fluctuations in
      visual perception.
AB  - Movement planning and execution rely on the anticipation and online control of
      the incoming sensory input. Evidence suggests that sensorimotor processes may
      synchronize visual rhythmic activity in preparation of action performance.
      Indeed, we recently reported periodic fluctuations of visual contrast sensitivity
      that are time-locked to the onset of an intended movement of the arm. However,
      the origin of the observed visual modulations has so far remained unclear because
      of the endogenous (and thus temporally undetermined) activation of the
      sensorimotor system that is associated with voluntary movement initiation. In
      this study, we activated the sensorimotor circuitry involved in the hand control
      in an exogenous and controlled way by means of peripheral stimulation of the
      median nerve and characterized the spectrotemporal dynamics of the ensuing visual
      perception. The stimulation of the median nerve triggers robust and long-lasting
      (~1 s) alpha-band oscillations in visual perception, whose strength is temporally
      modulated in a way that is consistent with the changes in alpha power described
      at the neurophysiological level after sensorimotor stimulation. These findings
      provide evidence in support of a causal role of the sensorimotor system in
      modulating oscillatory activity in visual areas with consequences for visual
      perception. NEW & NOTEWORTHY This study shows that the peripheral activation of
      the somatomotor hand system triggers long-lasting alpha periodicity in visual
      perception. This demonstrates that not only the endogenous sensorimotor processes
      involved in movement preparation but also the passive stimulation of the
      sensorimotor system can synchronize visual activity. The present work suggests
      that oscillation-based mechanisms may subserve core (task independent)
      sensorimotor integration functions.

PMID- 29046426
TI  - Phosphorylation of connexin 43 induced by traumatic brain injury promotes exosome
      release.
AB  - Traumatic brain injury (TBI) caused by the external force leads to the neuronal
      dysfunction and even death. TBI has been reported to significantly increase the
      phosphorylation of glial gap junction protein connexin 43 (Cx43), which in turn
      propagates damages into surrounding brain tissues. However, the neuroprotective
      and anti-apoptosis effects of glia-derived exosomes have also been implicated in
      recent studies. Therefore, we detected whether TBI-induced phosphorylation of
      Cx43 would promote exosome release in rat brain. To generate TBI model, adult
      male Sprague-Dawley rats were subjected to lateral fluid percussion injury.
      Phosphorylated Cx43 protein levels and exosome activities were quantified using
      Western blot analysis following TBI. Long-term potentiation (LTP) was also tested
      in rat hippocampal slices. TBI significantly increased the phosphorylated Cx43
      and exosome markers expression in rat ipsilateral hippocampus, but not cortex.
      Blocking the activity of Cx43 or ERK, but not JNK, significantly suppressed TBI
      induced exosome release in hippocampus. Furthermore, TBI significantly inhibited
      the induction of LTP in hippocampal slices, which could be partially but
      significantly restored by pretreatment with exosomes. The results imply that TBI
      activated Cx43 could mediate a nociceptive effect by propagating the brain
      damages, as well as a neuroprotective effect by promoting exosome release. NEW &
      NOTEWORTHY We have demonstrated in rat traumatic brain injury (TBI) models that
      both phosphorylated connexin 43 (p-Cx43) expression and exosome release were
      elevated in the hippocampus following TBI. The promoted exosome release depends
      on the phosphorylation of Cx43 and requires ERK signaling activation. Exosome
      treatment could partially restore the attenuated long-term potentiation. Our
      results provide new insight for future therapeutic direction on the functional
      recovery of TBI by promoting p-Cx43-dependent exosome release but limiting the
      gap junction-mediated bystander effect.

PMID- 29046425
TI  - Carotid chemoreceptors tune breathing via multipath routing: reticular chain and
      loop operations supported by parallel spike train correlations.
AB  - We tested the hypothesis that carotid chemoreceptors tune breathing through
      parallel circuit paths that target distinct elements of an inspiratory neuron
      chain in the ventral respiratory column (VRC). Microelectrode arrays were used to
      monitor neuronal spike trains simultaneously in the VRC, peri-nucleus tractus
      solitarius (p-NTS)-medial medulla, the dorsal parafacial region of the lateral
      tegmental field (FTL-pF), and medullary raphe nuclei together with phrenic nerve
      activity during selective stimulation of carotid chemoreceptors or transient
      hypoxia in 19 decerebrate, neuromuscularly blocked, and artificially ventilated
      cats. Of 994 neurons tested, 56% had a significant change in firing rate. A total
      of 33,422 cell pairs were evaluated for signs of functional interaction; 63% of
      chemoresponsive neurons were elements of at least one pair with correlational
      signatures indicative of paucisynaptic relationships. We detected evidence for
      postinspiratory neuron inhibition of rostral VRC I-Driver (pre-Botzinger)
      neurons, an interaction predicted to modulate breathing frequency, and for
      reciprocal excitation between chemoresponsive p-NTS neurons and more downstream
      VRC inspiratory neurons for control of breathing depth. Chemoresponsive
      pericolumnar tonic expiratory neurons, proposed to amplify inspiratory drive by
      disinhibition, were correlationally linked to afferent and efferent "chains" of
      chemoresponsive neurons extending to all monitored regions. The chains included
      coordinated clusters of chemoresponsive FTL-pF neurons with functional links to
      widespread medullary sites involved in the control of breathing. The results
      support long-standing concepts on brain stem network architecture and a circuit
      model for peripheral chemoreceptor modulation of breathing with multiple circuit
      loops and chains tuned by tegmental field neurons with quasi-periodic discharge
      patterns. NEW & NOTEWORTHY We tested the long-standing hypothesis that carotid
      chemoreceptors tune the frequency and depth of breathing through parallel circuit
      operations targeting the ventral respiratory column. Responses to stimulation of
      the chemoreceptors and identified functional connectivity support differential
      tuning of inspiratory neuron burst duration and firing rate and a model of brain
      stem network architecture incorporating tonic expiratory "hub" neurons regulated
      by convergent neuronal chains and loops through rostral lateral tegmental field
      neurons with quasi-periodic discharge patterns.

PMID- 29046427
TI  - Different contributions of primary motor cortex, reticular formation, and spinal
      cord to fractionated muscle activation.
AB  - Coordinated movement requires patterned activation of muscles. In this study, we
      examined differences in selective activation of primate upper limb muscles by
      cortical and subcortical regions. Five macaque monkeys were trained to perform a
      reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles
      while weak single-pulse stimuli were delivered through microelectrodes inserted
      in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC).
      Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked
      effects were assessed from averages of rectified EMG. M1, RF, and SC activated
      1.5 +/- 0.9, 1.9 +/- 0.8, and 2.5 +/- 1.6 muscles per site (means +/- SD); only
      M1 and SC differed significantly. In between recording sessions, natural muscle
      activity in the home cage was recorded using a miniature data logger. A novel
      analysis assessed how well natural activity could be reconstructed by stimulus
      evoked responses. This provided two measures: normalized vector length L,
      reflecting how closely aligned natural and stimulus-evoked activity were, and
      normalized residual R, measuring the fraction of natural activity not reachable
      using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1
      +/- 9.6, 105.9 +/- 6.2, and 109.3 +/- 8.4% and R = 50.3 +/- 4.9, 56.4 +/- 3.5,
      and 51.5 +/- 4.8%, respectively. RF was significantly different from M1 and SC on
      both measurements. RF is thus able to generate an approximation to the motor
      output with less activation than required by M1 and SC, but M1 and SC are more
      precise in reaching the exact activation pattern required. Cortical, brainstem,
      and spinal centers likely play distinct roles, as they cooperate to generate
      voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary
      motor cortex, and cervical spinal cord intermediate zone can all activate primate
      upper limb muscles. However, brainstem output is more efficient but less precise
      in producing natural patterns of motor output than motor cortex or spinal cord.
      We suggest that gross muscle synergies from the reticular formation are sculpted
      and refined by motor cortex and spinal circuits to reach the finely fractionated
      output characteristic of dexterous primate upper limb movements.

PMID- 29046428
TI  - Spatiotemporal characteristics of retinal response to network-mediated
      photovoltaic stimulation.
AB  - Subretinal prostheses aim at restoring sight to patients blinded by photoreceptor
      degeneration using electrical activation of the surviving inner retinal neurons.
      Today, such implants deliver visual information with low-frequency stimulation,
      resulting in discontinuous visual percepts. We measured retinal responses to
      complex visual stimuli delivered at video rate via a photovoltaic subretinal
      implant and by visible light. Using a multielectrode array to record from retinal
      ganglion cells (RGCs) in the healthy and degenerated rat retina ex vivo, we
      estimated their spatiotemporal properties from the spike-triggered average
      responses to photovoltaic binary white noise stimulus with 70-MUm pixel size at
      20-Hz frame rate. The average photovoltaic receptive field size was 194 +/- 3 MUm
      (mean +/- SE), similar to that of visual responses (221 +/- 4 MUm), but response
      latency was significantly shorter with photovoltaic stimulation. Both visual and
      photovoltaic receptive fields had an opposing center-surround structure. In the
      healthy retina, ON RGCs had photovoltaic OFF responses, and vice versa. This
      reversal is consistent with depolarization of photoreceptors by electrical
      pulses, as opposed to their hyperpolarization under increasing light, although
      alternative mechanisms cannot be excluded. In degenerate retina, both ON and OFF
      photovoltaic responses were observed, but in the absence of visual responses, it
      is not clear what functional RGC types they correspond to. Degenerate retina
      maintained the antagonistic center-surround organization of receptive fields.
      These fast and spatially localized network-mediated ON and OFF responses to
      subretinal stimulation via photovoltaic pixels with local return electrodes raise
      confidence in the possibility of providing more functional prosthetic vision. NEW
      & NOTEWORTHY Retinal prostheses currently in clinical use have struggled to
      deliver visual information at naturalistic frequencies, resulting in
      discontinuous percepts. We demonstrate modulation of the retinal ganglion cells
      (RGC) activity using complex spatiotemporal stimuli delivered via subretinal
      photovoltaic implant at 20 Hz in healthy and in degenerate retina. RGCs exhibit
      fast and localized ON and OFF network-mediated responses, with antagonistic
      center-surround organization of their receptive fields.

PMID- 29046429
TI  - Paired corticospinal-motoneuronal stimulation increases maximal voluntary
      activation of human adductor pollicis.
AB  - Paired corticospinal-motoneuronal stimulation (PCMS), which delivers repeated
      pairs of transcranial magnetic stimuli (TMS) and maximal motor nerve stimuli, can
      alter corticospinal transmission to low-threshold motoneurons in the human spinal
      cord. To determine whether similar changes occur for high-threshold motoneurons,
      we tested whether maximal voluntary activation and force can be affected by PCMS
      in healthy individuals. On 2 separate days, healthy participants ( n = 14)
      performed brief thumb adduction maximal voluntary contractions (MVCs) before and
      after a control protocol (TMS only) or PCMS designed to facilitate corticospinal
      transmission to adductor pollicis. Peripheral nerve stimulation alone was not
      performed. During each MVC, a superimposed twitch was elicited by a supramaximal
      stimulus delivered to the ulnar nerve. With muscles relaxed following the maximal
      contraction, a similar stimulus elicited a resting twitch. Voluntary activation
      was calculated as (1 - superimposed twitch/resting twitch) * 100%. Although
      voluntary activation decreased over time in both conditions, the decrease was
      less after PCMS (-0.4 +/- 4.1%) than after the control protocol (-4.9 +/- 4.9%; P
      = 0.007). This was supported by a greater increase in electromyographic response
      after PCMS than control (7 +/- 13% vs. -3 +/- 10%; P = 0.043). However, maximal
      force was not affected. The findings indicate a modest effect of PCMS on maximal
      neural drive to adductor pollicis, suggesting that PCMS can affect corticospinal
      transmission to high-threshold motoneurons. NEW & NOTEWORTHY Paired corticospinal
      motoneuronal stimulation (PCMS) induces changes in the human spinal cord. To
      date, the reported effects of PCMS have been limited to low-threshold motoneurons
      and low-force tasks in healthy and spinal cord injured individuals. For the first
      time, we show that these plastic changes are not limited to lower threshold
      motoneurons, but occur across the entire motoneuron pool as demonstrated by the
      increases in voluntary activation and muscle activity during maximal voluntary
      contractions of adductor pollicis.

PMID- 29046430
TI  - Path perturbation detection tasks reduce MSTd neuronal self-movement heading
      responses.
AB  - We presented optic flow and real movement heading stimuli while recording MSTd
      neuronal activity. Monkeys were alternately engaged in three tasks: visual
      detection of optic flow heading perturbations, vestibular detection of real
      movement heading perturbations, and auditory detection of brief tones. Push
      button RTs were fastest for tones and slower for visual and vestibular heading
      perturbations, suggesting that the tone detection task was easier. Neuronal
      heading selectivity was strongest during the tone detection task, and weaker
      during the visual and vestibular heading perturbation detection tasks. Heading
      selectivity was weaker during visual and vestibular path perturbation detection,
      despite our presented heading cues only in the visual and vestibular modalities.
      We conclude that focusing on the self-movement transients of path perturbation
      distracted the monkeys from their heading and reduced neuronal responsiveness to
      heading direction. NEW & NOTEWORTHY Heading analysis is critical for steering and
      navigation. We recorded the activity of monkey cortical heading neurons during
      naturalistic self-movement. When the monkeys were required to respond to
      transient changes in their path, neuronal responses to heading direction were
      diminished. This suggests that the need to respond to momentary path
      perturbations reduces your ability to process your heading direction.

PMID- 29046431
TI  - A Survey of Perceived Effectiveness of Part 4 Maintenance of Certification.
AB  - OBJECTIVES: Evaluative assessment is needed to inform improvement of Part 4
      Maintenance of Certification (MOC), a large-scale program that aims to improve
      physician knowledge, engagement, and skills in quality improvement (QI). We
      sought to determine if Part 4 MOC participation improves perceived educational
      and clinical outcomes by piloting a new physician survey. METHODS: We
      administered a new online survey (MOC Practice, Engagement, Attitude, and
      Knowledge Survey) to physicians at the beginning and end of a Part 4 MOC project
      sponsored by a pediatric hospital's American Board of Medical Specialties'
      portfolio program during 2015. Participants worked in academic and community
      settings and in various accredited specialties. The main outcome was change in
      survey response on a 5-point Likert scale (1 = best) for 3 learning domains (QI
      engagement and attitude; QI method application, and improved patient care).
      RESULTS: Of 123 complete responses and a 97% response rate, mean baseline
      responses were positive or neutral (2.2, 2.3, 1.9, respectively). Responses
      improved in QI engagement and attitude (-0.15, z score = -2.78, P = .005), QI
      method application (-0.39, z score = -7.364, P < .005), and improved patient care
      (-0.11, z score = -1.728, P = .084). CONCLUSIONS: A Part 4 MOC physician survey
      provides valuable data to evaluate and improve the learning activity. In this
      children's hospital program, physicians view Part 4 favorably. Participation was
      associated with modest improvements in perceptions of QI engagement and attitude,
      application of QI methods, and patient care. Systematic evaluation of all Part 4
      MOC projects and programs has the potential to improve the program nationally.

PMID- 29046432
TI  - ALK is a therapeutic target for lethal sepsis.
AB  - Sepsis, a life-threatening organ dysfunction caused by infection, is a major
      public health concern with limited therapeutic options. We provide evidence to
      support a role for anaplastic lymphoma kinase (ALK), a tumor-associated receptor
      tyrosine kinase, in the regulation of innate immunity during lethal sepsis. The
      genetic disruption of ALK expression diminishes the stimulator of interferon
      genes (STING)-mediated host immune response to cyclic dinucleotides in monocytes
      and macrophages. Mechanistically, ALK directly interacts with epidermal growth
      factor receptor (EGFR) to trigger serine-threonine protein kinase AKT
      phosphorylation and activate interferon regulatory factor 3 (IRF3) and nuclear
      factor kappaB (NF-kappaB) signaling pathways, enabling STING-dependent rigorous
      inflammatory responses. Moreover, pharmacological or genetic inhibition of the
      ALK-STING pathway confers protection against lethal endotoxemia and sepsis in
      mice. The ALK pathway is up-regulated in patients with sepsis. These findings
      uncover a key role for ALK in modulating the inflammatory signaling pathway and
      shed light on the development of ALK-targeting therapeutics for lethal systemic
      inflammatory disorders.

PMID- 29046433
TI  - A multimechanistic antibody targeting the receptor binding site potently cross
      protects against influenza B viruses.
AB  - Influenza B virus causes considerable disease burden worldwide annually,
      highlighting the limitations of current influenza vaccines and antiviral drugs.
      In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin
      (HA) have emerged as a new approach for combating influenza. We describe the
      generation and characterization of a chimeric monoclonal antibody, C12G6, that
      cross-neutralizes representative viruses spanning the 76 years of influenza B
      antigenic evolution since 1940, including viruses belonging to the Yamagata,
      Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage
      hemagglutination inhibition activity against influenza B viruses and has higher
      potency and breadth of neutralization when compared to four previously reported
      influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against
      Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than
      other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral
      effect when administered in combination with oseltamivir. Epitope mapping
      indicated that C12G6 targets a conserved epitope that overlaps with the receptor
      binding site in the HA region of influenza B virus, indicating why it neutralizes
      virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B
      viruses via multiple mechanisms, including preventing viral entry, egress, and HA
      mediated membrane fusion and triggering antibody-dependent cell-mediated
      cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore
      a promising candidate for the development of prophylactics or therapeutics
      against influenza B infection and may inform the design of a truly universal
      influenza vaccine.

PMID- 29046434
TI  - Aristolochic acids and their derivatives are widely implicated in liver cancers
      in Taiwan and throughout Asia.
AB  - Many traditional pharmacopeias include Aristolochia and related plants, which
      contain nephrotoxins and mutagens in the form of aristolochic acids and similar
      compounds (collectively, AA). AA is implicated in multiple cancer types,
      sometimes with very high mutational burdens, especially in upper tract urothelial
      cancers (UTUCs). AA-associated kidney failure and UTUCs are prevalent in Taiwan,
      but AA's role in hepatocellular carcinomas (HCCs) there remains unexplored.
      Therefore, we sequenced the whole exomes of 98 HCCs from two hospitals in Taiwan
      and found that 78% showed the distinctive mutational signature of AA exposure,
      accounting for most of the nonsilent mutations in known cancer driver genes. We
      then searched for the AA signature in 1400 HCCs from diverse geographic regions.
      Consistent with exposure through known herbal medicines, 47% of Chinese HCCs
      showed the signature, albeit with lower mutation loads than in Taiwan. In
      addition, 29% of HCCs from Southeast Asia showed the signature. The AA signature
      was also detected in 13 and 2.7% of HCCs from Korea and Japan as well as in 4.8
      and 1.7% of HCCs from North America and Europe, respectively, excluding one U.S.
      hospital where 22% of 87 "Asian" HCCs had the signature. Thus, AA exposure is
      geographically widespread. Asia, especially Taiwan, appears to be much more
      extensively affected, which is consistent with other evidence of patterns of AA
      exposure. We propose that additional measures aimed at primary prevention through
      avoidance of AA exposure and investigation of possible approaches to secondary
      prevention are warranted.

PMID- 29046435
TI  - Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to
      monkeys.
AB  - In search of metabolically regulated secreted proteins, we conducted a microarray
      study comparing gene expression in major metabolic tissues of fed and fasted
      ob/ob mice and C57BL/6 mice. The array used in this study included probes for
      ~4000 genes annotated as potential secreted proteins. Circulating macrophage
      inhibitory cytokine 1 (MIC-1)/growth differentiation factor 15 (GDF15)
      concentrations were increased in obese mice, rats, and humans in comparison to
      age-matched lean controls. Adeno-associated virus-mediated overexpression of
      GDF15 and recombinant GDF15 treatments reduced food intake and body weight and
      improved metabolic profiles in various metabolic disease models in mice, rats,
      and obese cynomolgus monkeys. Analysis of the GDF15 crystal structure suggested
      that the protein is not suitable for conventional Fc fusion at the carboxyl
      terminus of the protein. Thus, we used a structure-guided approach to design and
      successfully generate several Fc fusion molecules with extended half-life and
      potent efficacy. Furthermore, we discovered that GDF15 delayed gastric emptying,
      changed food preference, and activated area postrema neurons, confirming a role
      for GDF15 in the gut-brain axis responsible for the regulation of body energy
      intake. Our work provides evidence that GDF15 Fc fusion proteins could be
      potential therapeutic agents for the treatment of obesity and related
      comorbidities.

PMID- 29046436
TI  - Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint
      Components Are Required for Genome Stability in Response to Treatment with
      Ionizing Radiation.
AB  - Relatively little is known about the cross-talk between the spindle assembly
      checkpoint and the DNA damage response, especially in multicellular organisms. We
      performed a Caenorhabditis elegans forward genetic screen to uncover new genes
      involved in the repair of DNA damage induced by ionizing radiation. We isolated a
      mutation, gt2000, which confers hypersensitivity to ionizing radiation and showed
      that gt2000 introduces a premature stop in bub-3 BUB-3 is a key component of the
      spindle assembly checkpoint. We provide evidence that BUB-3 acts during
      development and in the germline; irradiated bub-3(gt2000) larvae are
      developmentally retarded and form abnormal vulvae. Moreover, bub-3(gt2000)
      embryos sired from irradiated worms show increased levels of lethality. Both bub
      3 and san-1 (the C. elegans homolog of MAD3) deletion alleles confer
      hypersensitivity to ionizing radiation, consistent with the notion that the
      spindle assembly checkpoint pathway is required for the DNA damage response. bub
      3(gt2000) is moderately sensitive to the cross-linking drug cisplatin but not to
      ultraviolet light or methyl methanesulfonate. This is consistent with a role in
      dealing with DNA double-strand breaks and not with base damage. Double mutant
      analysis revealed that bub-3 does not act within any of the three major pathways
      involved in the repair of double-strand breaks. Finally, the cdc-20 gain-of
      function mutant cdc-20/fzy-1(av15), which is refractory to the cell cycle delay
      conferred by the spindle checkpoint, showed phenotypes similar to bub-3 and san-1
      mutants. We speculate that BUB-3 is involved in the DNA damage response through
      regulation of cell cycle timing.

PMID- 29046438
TI  - On Myelinated Axon Plasticity and Neuronal Circuit Formation and Function.
AB  - Studies of activity-driven nervous system plasticity have primarily focused on
      the gray matter. However, MRI-based imaging studies have shown that white matter,
      primarily composed of myelinated axons, can also be dynamically regulated by
      activity of the healthy brain. Myelination in the CNS is an ongoing process that
      starts around birth and continues throughout life. Myelin in the CNS is generated
      by oligodendrocytes and recent evidence has shown that many aspects of
      oligodendrocyte development and myelination can be modulated by extrinsic signals
      including neuronal activity. Because modulation of myelin can, in turn, affect
      several aspects of conduction, the concept has emerged that activity-regulated
      myelination represents an important form of nervous system plasticity. Here we
      review our increasing understanding of how neuronal activity regulates
      oligodendrocytes and myelinated axons in vivo, with a focus on the timing of
      relevant processes. We highlight the observations that neuronal activity can
      rapidly tune axonal diameter, promote re-entry of oligodendrocyte progenitor
      cells into the cell cycle, or drive their direct differentiation into
      oligodendrocytes. We suggest that activity-regulated myelin formation and
      remodeling that significantly change axonal conduction properties are most likely
      to occur over timescales of days to weeks. Finally, we propose that precise fine
      tuning of conduction along already-myelinated axons may also be mediated by
      alterations to the axon itself. We conclude that future studies need to analyze
      activity-driven adaptations to both axons and their myelin sheaths to fully
      understand how myelinated axon plasticity contributes to neuronal circuit
      formation and function.

PMID- 29046437
TI  - Modulation of Global Transcriptional Regulatory Networks as a Strategy for
      Increasing Kanamycin Resistance of the Translational Elongation Factor-G Mutants
      in Escherichia coli.
AB  - Evolve and resequence experiments have provided us a tool to understand bacterial
      adaptation to antibiotics. In our previous work, we used short-term evolution to
      isolate mutants resistant to the ribosome targeting antibiotic kanamycin, and
      reported that Escherichia coli develops low cost resistance to kanamycin via
      different point mutations in the translation Elongation Factor-G (EF-G).
      Furthermore, we had shown that the resistance of EF-G mutants could be increased
      by second site mutations in the genes rpoD/cpxA/topA/cyaA Mutations in three of
      these genes had been discovered in earlier screens for aminoglycoside resistance.
      In this work, we expand our understanding of these second site mutations, the
      goal being to understand how these mutations affect the activities of the mutated
      gene products to confer resistance. We show that the mutation in cpxA most likely
      results in an active Cpx stress response. Further evolution of an EF-G mutant in
      a higher concentration of kanamycin than what was used in our previous
      experiments identified the cpxA locus as a primary target for a significant
      increase in resistance. The mutation in cyaA results in a loss of catalytic
      activity and probably results in resistance via altered CRP function. Despite a
      reduction in cAMP levels, the CyaAN600Y mutant has a transcriptome indicative of
      increased CRP activity, pointing to an unknown role for CyaA and / or cAMP in
      gene expression. From the transcriptomes of double and single mutants, we
      describe the epistasis between the mutation in EF-G and these second site
      mutations. We show that the large scale transcriptomic changes in the
      topoisomerase I (FusAA608E-TopAS180L) mutant likely result from increased
      negative supercoiling in the cell. Finally, genes with known roles in
      aminoglycoside resistance were present among the misregulated genes in the
      mutants.

PMID- 29046439
TI  - Stress and Exploitative Decision-Making.

PMID- 29046440
TI  - Innate Sensing of Influenza A Virus Hemagglutinin Glycoproteins by the Host
      Endoplasmic Reticulum (ER) Stress Pathway Triggers a Potent Antiviral Response
      via ER-Associated Protein Degradation.
AB  - Innate immunity provides an immediate defense against infection after host cells
      sense danger signals from microbes. Endoplasmic reticulum (ER) stress arises from
      accumulation of misfolded/unfolded proteins when protein load overwhelms the ER
      folding capacity, which activates the unfolded protein response (UPR) to restore
      ER homeostasis. Here, we show that a mechanism for antiviral innate immunity is
      triggered after the ER stress pathway senses viral glycoproteins. When
      hemagglutinin (HA) glycoproteins from influenza A virus (IAV) are expressed in
      cells, ER stress is induced, resulting in rapid HA degradation via proteasomes.
      The ER-associated protein degradation (ERAD) pathway, an important UPR function
      for destruction of aberrant proteins, mediates HA degradation. Three class I
      alpha-mannosidases were identified to play a critical role in the degradation
      process, including EDEM1, EDEM2, and ERManI. HA degradation requires either
      ERManI enzymatic activity or EDEM1/EDEM2 enzymatic activity when ERManI is not
      expressed, indicating that demannosylation is a critical step for HA degradation.
      Silencing of EDEM1, EDEM2, and ERManI strongly increases HA expression and
      promotes IAV replication. Thus, the ER stress pathway senses influenza HA as
      "nonself" or misfolded protein and sorts HA to ERAD for degradation, resulting in
      inhibition of IAV replication.IMPORTANCE Viral nucleic acids are recognized as
      important inducers of innate antiviral immune responses that are sensed by
      multiple classes of sensors, but other inducers and sensors of viral innate
      immunity need to be identified and characterized. Here, we used IAV to
      investigate how host innate immunity is activated. We found that IAV HA
      glycoproteins induce ER stress, resulting in HA degradation via ERAD and
      consequent inhibition of IAV replication. In addition, we have identified three
      class I alpha-mannosidases, EDEM1, EDEM2, and ERManI, which play a critical role
      in initiating HA degradation. Knockdown of these proteins substantially increases
      HA expression and IAV replication. The enzymatic activities and joint actions of
      these mannosidases are required for this antiviral activity. Our results suggest
      that viral glycoproteins induce a strong innate antiviral response through
      activating the ER stress pathway during viral infection.

PMID- 29046441
TI  - Structure-function dissection of the Pseudorabies virus glycoprotein B fusion
      loops.
AB  - Conserved across the Herpesviridae family, glycoprotein B (gB) is responsible for
      driving fusion of the viral envelope with the host cell membrane for entry upon
      receptor binding and activation by the viral gH/gL complex. Although crystal
      structures of the gB ectodomain of several herpesviruses have been reported, the
      membrane fusion mechanism has remained elusive. Here, we report the X-ray
      structure of the Pseudorabies virus (PrV) gB ectodomain, revealing a typical
      class III post-fusion trimer that binds membranes via its fusion loops (FLs) in a
      cholesterol-dependent manner. Mutagenesis of FL residues allowed us to dissect
      those interacting with distinct sub-regions of the lipid bilayer and their role
      for membrane interactions. We tested 15 gB variants for their ability to bind to
      liposomes, and further investigated a subset of them in functional assays. We
      found that PrV gB FL residues Trp187, Tyr192, Phe275 and Tyr276, which were
      essential for liposome binding and for fusion in a cellular and viral context,
      form a continuous hydrophobic patch at the gB trimer surface. Together with
      reported results from other alpha-herpesvirus gBs, our data suggest a model in
      which Phe275 from the tip of FL2 protrudes deeper into the hydrocarbon core of
      the lipid bilayer, while the side chains of Trp187, Tyr192 and Tyr276 form a rim
      that inserts into the more superficial, interfacial region of the membrane to
      catalyze the fusion process. Comparative analysis with gB from beta- and gamma
      herpesviruses suggest that this membrane-interaction mode is valid for gB from
      all herpesviruses.IMPORTANCE Herpesviruses are common human and animal pathogens,
      which infect cells by entering via fusion of viral and cellular membranes and
      which cause life-long and incurable infections. Central to the membrane fusion
      event for entry is glycoprotein B (gB), which is the most conserved envelope
      protein across the herpesvirus family. Like other viral fusion proteins, gB
      anchors itself into the target membrane via two polypeptide segments called
      fusion loops (FL). The molecular details of how gB FLs insert into the lipid
      bilayer have not been described. We provide here structural and functional data
      regarding key FL residues of gB from Pseudorabies virus, a porcine herpesvirus of
      veterinary concern, which allows us to propose, for the first time, a molecular
      model to understand how the initial interactions by gB from all herpesviruses
      with target membranes are established.

PMID- 29046442
TI  - Rice Stripe Tenuivirus Has a Greater Tendency To Use the Prime-and-Realign
      Mechanism in Transcription of Genomic than in Transcription of Antigenomic
      Template RNAs.
AB  - Most segmented negative-sense RNA viruses employ a process termed cap snatching,
      during which they snatch capped RNA leaders from host cellular mRNAs and use the
      snatched leaders as primers for transcription, leading to the synthesis of viral
      mRNAs with 5' heterogeneous sequences (HSs). With traditional methods, only a few
      HSs can be determined, and identification of their donors is difficult. Here, the
      mRNA 5' ends of Rice stripe tenuivirus (RSV) and Rice grassy stunt tenuivirus
      (RGSV) and those of their host rice were determined by high-throughput
      sequencing. Millions of tenuiviral HSs were obtained, and a large number of them
      mapped to the 5' ends of corresponding host cellular mRNAs. Repeats of the
      dinucleotide AC, which are complementary to the U1G2 of the tenuiviral template
      3'-U1G2U3G4UUUCG, were found to be prevalent at the 3' termini of tenuiviral HSs.
      Most of these ACs did not match host cellular mRNAs, supporting the idea that
      tenuiviruses use the prime-and-realign mechanism during cap snatching. We
      previously reported a greater tendency of RSV than RGSV to use the prime-and
      realign mechanism in transcription with leaders cap snatched from a coinfecting
      reovirus. Besides confirming this observation in natural tenuiviral infections,
      the data here additionally reveal that RSV has a greater tendency to use this
      mechanism in transcribing genomic than in transcribing antigenomic templates. The
      data also suggest that tenuiviruses cap snatch host cellular mRNAs from
      translation- and photosynthesis-related genes, and capped RNA leaders snatched by
      tenuiviruses base pair with U1/U3 or G2/G4 of viral templates. These results
      provide unprecedented insights into the cap-snatching process of
      tenuiviruses.IMPORTANCE Many segmented negative-sense RNA viruses (segmented
      NSVs) are medically or agriculturally important pathogens. The cap-snatching
      process is a promising target for the development of antiviral strategies against
      this group of viruses. However, many details of this process remain poorly
      characterized. Tenuiviruses constitute a genus of agriculturally important
      segmented NSVs, several members of which are major viral pathogens of rice. Here,
      we for the first time adopted a high-throughput sequencing strategy to determine
      the 5' heterogeneous sequences (HSs) of tenuiviruses and mapped them to host
      cellular mRNAs. Besides providing deep insights into the cap snatching of
      tenuiviruses, the data obtained provide clear evidence to support several
      previously proposed models regarding cap snatching. Curiously and importantly,
      the data here reveal that not only different tenuiviruses but also the same
      tenuivirus synthesizing different mRNAs use the prime-and-realign mechanism with
      different tendencies during their cap snatching.

PMID- 29046443
TI  - Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform
      Encephalopathy Pathogenesis in Mice.
AB  - Conformational conversion of the cellular isoform of prion protein, PrPC, into
      the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in
      prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and
      bovine spongiform encephalopathy (BSE) in animals. We previously reported that
      the octapeptide repeat (OR) region could be dispensable for converting PrPC into
      PrPSc after infection with RML prions. We demonstrated that mice transgenically
      expressing mouse PrP with deletion of the OR region on the PrP knockout
      background, designated Tg(PrPDeltaOR)/Prnp0/0 mice, did not show reduced
      susceptibility to RML scrapie prions, with abundant accumulation of PrPScDeltaOR
      in their brains. We show here that Tg(PrPDeltaOR)/Prnp0/0 mice were highly
      resistant to BSE prions, developing the disease with markedly elongated
      incubation times after infection with BSE prions. The conversion of PrPDeltaOR
      into PrPScDeltaOR was markedly delayed in their brains. These results suggest
      that the OR region may have a crucial role in the conversion of PrPC into PrPSc
      after infection with BSE prions. However, Tg(PrPDeltaOR)/Prnp0/0 mice remained
      susceptible to RML and 22L scrapie prions, developing the disease without
      elongated incubation times after infection with RML and 22L prions. PrPScDeltaOR
      accumulated only slightly less in the brains of RML- or 22L-infected
      Tg(PrPDeltaOR)/Prnp0/0 mice than PrPSc in control wild-type mice. Taken together,
      these results indicate that the OR region of PrPC could play a differential role
      in the pathogenesis of BSE prions and RML or 22L scrapie prions.IMPORTANCE
      Structure-function relationship studies of PrPC conformational conversion into
      PrPSc are worthwhile to understand the mechanism of the conversion of PrPC into
      PrPSc We show here that, by inoculating Tg(PrPDeltaOR)/Prnp0/0 mice with the
      three different strains of RML, 22L, and BSE prions, the OR region could play a
      differential role in the conversion of PrPC into PrPSc after infection with RML
      or 22L scrapie prions and BSE prions. PrPDeltaOR was efficiently converted into
      PrPScDeltaOR after infection with RML and 22L prions. However, the conversion of
      PrPDeltaOR into PrPScDeltaOR was markedly delayed after infection with BSE
      prions. Further investigation into the role of the OR region in the conversion of
      PrPC into PrPSc after infection with BSE prions might be helpful for
      understanding the pathogenesis of BSE prions.

PMID- 29046444
TI  - Resistance of Major Histocompatibility Complex Class B (MHC-B) to Nef-Mediated
      Downregulation Relative to that of MHC-A Is Conserved among Primate Lentiviruses
      and Influences Antiviral T Cell Responses in HIV-1-Infected Individuals.
AB  - Patient-derived HIV-1 subtype B Nef clones downregulate HLA-A more efficiently
      than HLA-B. However, it remains unknown whether this property is common to Nef
      proteins across primate lentiviruses and how antiviral immune responses may be
      affected. We examined 263 Nef clones from diverse primate lentiviruses including
      different pandemic HIV-1 group M subtypes for their ability to downregulate major
      histocompatibility complex class A (MHC-A) and MHC-B from the cell surface.
      Though lentiviral Nef proteins differed markedly in their absolute MHC-A and MHC
      B downregulation abilities, all lentiviral Nef lineages downregulated MHC-A, on
      average, 11 to 32% more efficiently than MHC-B. Nef genotype/phenotype analyses
      in a cohort of HIV-1 subtype C-infected patients (n = 168), together with site
      directed mutagenesis, revealed Nef position 9 as a subtype-specific determinant
      of differential HLA-A versus HLA-B downregulation activity. Nef clones harboring
      nonconsensus variants at codon 9 downregulated HLA-B (though not HLA-A)
      significantly better than those harboring the consensus sequence at this site,
      resulting in reduced recognition of infected target cells by HIV-1-specific CD8+
      effector cells in vitro Among persons expressing protective HLA class I alleles,
      carriage of Nef codon 9 variants was also associated with reduced ex vivo HIV
      specific T cell responses. Our results demonstrate that Nef's inferior ability to
      downregulate MHC-B compared to that of MHC-A is conserved across primate
      lentiviruses and suggest that this property influences antiviral cellular immune
      responses.IMPORTANCE Primate lentiviruses encode the Nef protein that plays an
      essential role in establishing persistent infection in their respective host
      species. Nef interacts with the cytoplasmic region of MHC-A and MHC-B molecules
      and downregulates them from the infected cell surface to escape recognition by
      host cellular immunity. Using a panel of Nef alleles isolated from diverse
      primate lentiviruses including pandemic HIV-1 group M subtypes, we demonstrate
      that Nef proteins across all lentiviral lineages downregulate MHC-A approximately
      20% more effectively than MHC-B. We further identify a naturally polymorphic site
      at Nef position 9 that contributes to the MHC-B downregulation function in HIV-1
      subtype C and show that carriage of Nef variants with enhanced MHC-B
      downregulation ability is associated with reduced breadth and magnitude of MHC-B
      restricted cellular immune responses in HIV-infected individuals. Our study
      underscores an evolutionarily conserved interaction between lentiviruses and
      primate immune systems that may contribute to pathogenesis.

PMID- 29046445
TI  - Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus
      Diversity and Evolution.
AB  - Until fairly recently, genome-wide evolutionary dynamics and within-host
      diversity were more commonly examined in the context of small viruses than in the
      context of large double-stranded DNA viruses such as herpesviruses. The high
      mutation rates and more compact genomes of RNA viruses have inspired the
      investigation of population dynamics for these species, and recent data now
      suggest that herpesviruses might also be considered candidates for population
      modeling. High-throughput sequencing (HTS) and bioinformatics have expanded our
      understanding of herpesviruses through genome-wide comparisons of sequence
      diversity, recombination, allele frequency, and selective pressures. Here we
      discuss recent data on the mechanisms that generate herpesvirus genomic diversity
      and underlie the evolution of these virus families. We focus on human
      herpesviruses, with key insights drawn from veterinary herpesviruses and other
      large DNA virus families. We consider the impacts of cell culture on herpesvirus
      genomes and how to accurately describe the viral populations under study. The
      need for a strong foundation of high-quality genomes is also discussed, since it
      underlies all secondary genomic analyses such as RNA sequencing (RNA-Seq),
      chromatin immunoprecipitation, and ribosome profiling. Areas where we foresee
      future progress, such as the linking of viral genetic differences to phenotypic
      or clinical outcomes, are highlighted as well.

PMID- 29046446
TI  - Foamy Virus Vector Carries a Strong Insulator in Its Long Terminal Repeat Which
      Reduces Its Genotoxic Potential.
AB  - Strong viral enhancers in gammaretrovirus vectors have caused cellular proto
      oncogene activation and leukemia, necessitating the use of cellular promoters in
      "enhancerless" self-inactivating integrating vectors. However, cellular promoters
      result in relatively low transgene expression, often leading to inadequate
      disease phenotype correction. Vectors derived from foamy virus, a nonpathogenic
      retrovirus, show higher preference for nongenic integrations than
      gammaretroviruses/lentiviruses and preferential integration near transcriptional
      start sites, like gammaretroviruses. We found that strong viral
      enhancers/promoters placed in foamy viral vectors caused extremely low
      immortalization of primary mouse hematopoietic stem/progenitor cells compared to
      analogous gammaretrovirus/lentivirus vectors carrying the same
      enhancers/promoters, an effect not explained solely by foamy virus' modest
      insertional site preference for nongenic regions compared to
      gammaretrovirus/lentivirus vectors. Using CRISPR/Cas9-mediated targeted insertion
      of analogous proviral sequences into the LMO2 gene and then measuring LMO2
      expression, we demonstrate a sequence-specific effect of foamy virus, independent
      of insertional bias, contributing to reduced genotoxicity. We show that this
      effect is mediated by a 36-bp insulator located in the foamy virus long terminal
      repeat (LTR) that has high-affinity binding to the CCCTC-binding factor. Using
      our LMO2 activation assay, LMO2 expression was significantly increased when this
      insulator was removed from foamy virus and significantly reduced when the
      insulator was inserted into the lentiviral LTR. Our results elucidate a mechanism
      underlying the low genotoxicity of foamy virus, identify a novel insulator, and
      support the use of foamy virus as a vector for gene therapy, especially when
      strong enhancers/promoters are required.IMPORTANCE Understanding the genotoxic
      potential of viral vectors is important in designing safe and efficacious vectors
      for gene therapy. Self-inactivating vectors devoid of viral long-terminal-repeat
      enhancers have proven safe; however, transgene expression from cellular promoters
      is often insufficient for full phenotypic correction. Foamy virus is an
      attractive vector for gene therapy. We found foamy virus vectors to be remarkably
      less genotoxic, well below what was expected from their integration site
      preferences. We demonstrate that the foamy virus long terminal repeats contain an
      insulator element that binds CCCTC-binding factor and reduces its insertional
      genotoxicity. Our study elucidates a mechanism behind the low genotoxic potential
      of foamy virus, identifies a unique insulator, and supports the use of foamy
      virus as a vector for gene therapy.

PMID- 29046447
TI  - Functional Carboxy-Terminal Fluorescent Protein Fusion to Pseudorabies Virus
      Small Capsid Protein VP26.
AB  - Fluorescent protein fusions to herpesvirus capsids have proven to be a valuable
      method to study virus particle transport in living cells. Fluorescent protein
      fusions to the amino terminus of small capsid protein VP26 are the most widely
      used method to visualize pseudorabies virus (PRV) and herpes simplex virus (HSV)
      particles in living cells. However, these fusion proteins do not incorporate to
      full occupancy and have modest effects on virus replication and pathogenesis.
      Recent cryoelectron microscopy studies have revealed that herpesvirus small
      capsid proteins bind to capsids via their amino terminus, whereas the carboxy
      terminus is unstructured and therefore may better tolerate fluorescent protein
      fusions. Here, we describe a new recombinant PRV expressing a carboxy-terminal
      VP26-mCherry fusion. Compared to previously characterized viruses expressing
      amino-terminal fusions, this virus expresses more VP26 fusion protein in infected
      cells and incorporates more VP26 fusion protein into virus particles, and
      individual virus particles exhibit brighter red fluorescence. We performed single
      particle tracking of fluorescent virus particles in primary neurons to measure
      anterograde and retrograde axonal transport, demonstrating the usefulness of this
      novel VP26-mCherry fusion for the study of viral intracellular
      transport.IMPORTANCE Alphaherpesviruses are among the very few viruses that are
      adapted to invade the mammalian nervous system. Intracellular transport of virus
      particles in neurons is important, as this process underlies both mild peripheral
      nervous system infection and severe spread to the central nervous system. VP26,
      the small capsid protein of HSV and PRV, was one of the first herpesvirus
      proteins to be fused to a fluorescent protein. Since then, these capsid-tagged
      virus mutants have become a powerful tool to visualize and track individual virus
      particles. Improved capsid tags will facilitate fluorescence microscopy studies
      of virus particle intracellular transport, as a brighter particle will improve
      localization accuracy of individual particles and allow for shorter exposure
      times, reducing phototoxicity and improving the time resolution of particle
      tracking in live cells.

PMID- 29046448
TI  - In Vitro Neutralization Is Not Predictive of Prophylactic Efficacy of Broadly
      Neutralizing Monoclonal Antibodies CR6261 and CR9114 against Lethal H2 Influenza
      Virus Challenge in Mice.
AB  - Influenza viruses of the H1N1, H2N2, and H3N2 subtypes have caused previous
      pandemics. H2 influenza viruses represent a pandemic threat due to continued
      circulation in wild birds and limited immunity in the human population. In the
      event of a pandemic, antiviral agents are the mainstay for treatment, but broadly
      neutralizing antibodies (bNAbs) may be a viable alternative for short-term
      prophylaxis or treatment. The hemagglutinin stem binding bNAbs CR6261 and CR9114
      have been shown to protect mice from severe disease following challenge with H1N1
      and H5N1 and with H1N1, H3N2, and influenza B viruses, respectively. Early
      studies with CR6261 and CR9114 showed weak in vitro activity against human H2
      influenza viruses, but the in vivo efficacy against H2 viruses is unknown.
      Therefore, we evaluated these antibodies against human- and animal-origin H2
      viruses A/Ann Arbor/6/1960 (H2N2) (AA60) and A/swine/MO/4296424/06 (H2N3) (Sw06).
      In vitro, CR6261 neutralized both H2 viruses, while CR9114 only neutralized Sw06.
      To evaluate prophylactic efficacy, mice were given CR6261 or CR9114 and
      intranasally challenged 24 h later with lethal doses of AA60 or Sw06. Both
      antibodies reduced mortality, weight loss, airway inflammation, and pulmonary
      viral load. Using engineered bNAb variants, antibody-mediated cell cytotoxicity
      reporter assays, and Fcgamma receptor-deficient (Fcer1g-/-) mice, we show that
      the in vivo efficacy of CR9114 against AA60 is mediated by Fcgamma receptor
      dependent mechanisms. Collectively, these findings demonstrate the in vivo
      efficacy of CR6261 and CR9114 against H2 viruses and emphasize the need for in
      vivo evaluation of bNAbs.IMPORTANCE bNAbs represent a strategy to prevent or
      treat infection by a wide range of influenza viruses. The evaluation of these
      antibodies against H2 viruses is important because H2 viruses caused a pandemic
      in 1957 and could cross into humans again. We demonstrate that CR6261 and CR9114
      are effective against infection with H2 viruses of both human and animal origin
      in mice, despite the finding that CR9114 did not display in vitro neutralizing
      activity against the human H2 virus. These findings emphasize the importance of
      in vivo evaluation and testing of bNAbs.

PMID- 29046450
TI  - Distribution of Hepatitis B Virus Nuclear DNA.
AB  - Chronic hepatitis B affects over 300 million people who are at risk of developing
      liver cancer. The basis for the persistence of hepatitis B virus (HBV) in
      hepatocytes, even in the presence of available antiviral therapies, lies in the
      accumulation of covalently closed circular DNA (cccDNA) in nuclei of infected
      cells. While methods for cccDNA quantification from liver biopsy specimens and
      cell lines expressing the virus are known, information about cccDNA formation,
      stability, and turnover is lacking. In particular, little is known about the fate
      of cccDNA during cell division. To fill the gaps in knowledge concerning cccDNA
      biology, we have developed a fluorescence imaging in situ hybridization (FISH)
      based assay for the detection of duck hepatitis B virus (DHBV) cccDNA and HBV
      nuclear DNA in established cell lines. Using FISH, we determined the distribution
      of cccDNA under conditions mimicking chronic infections with and without
      antiviral therapy, which prevents de novo viral replication. Our results showed
      that the copy numbers of viral nuclear DNA can vary by as much as 1.8 orders of
      magnitude among individual cells and that antiviral therapy leads to a reduction
      in nuclear DNA in a manner consistent with symmetrical distribution of viral DNA
      to daughter cells.IMPORTANCE A mechanistic understanding of the stability of HBV
      cccDNA in the presence of antiviral therapy and during cell division induced by
      immune-mediated lysis of infected hepatocytes will be critical for the future
      design of curative antiviral therapies against chronic hepatitis B. Current
      knowledge about cccDNA stability was largely derived from quantitative analyses
      of cccDNA levels present in liver samples, and little was known about the fate of
      cccDNA in individual cells. The development of a FISH-based assay for cccDNA
      tracking provided the first insights into the fate of DHBV cccDNA and nuclear HBV
      DNA under conditions mimicking antiviral therapy.

PMID- 29046449
TI  - MicroRNA gga-miR-130b Suppresses Infectious Bursal Disease Virus Replication via
      Targeting of the Viral Genome and Cellular Suppressors of Cytokine Signaling 5.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression
      posttranscriptionally through silencing or degrading their targets, thus playing
      important roles in the immune response. However, the role of miRNAs in the host
      response against infectious bursal disease virus (IBDV) infection is not clear.
      In this study, we show that the expression of a series of miRNAs was
      significantly altered in DF-1 cells after IBDV infection. We found that the miRNA
      gga-miR-130b inhibited IBDV replication via targeting the specific sequence of
      IBDV segment A and enhanced the expression of beta interferon (IFN-beta) by
      targeting suppressors of cytokine signaling 5 (SOCS5) in host cells. These
      findings indicate that gga-miR-130b-3p plays a crucial role in host defense
      against IBDV infection.IMPORTANCE This work shows that gga-miR-130b suppresses
      IBDV replication via directly targeting the viral genome and cellular SOCS5, the
      negative regulator for type I interferon expression, revealing the mechanism
      underlying gga-miR-130-induced inhibition of IBDV replication. This information
      will be helpful for the understanding of how host cells combat pathogenic
      infection by self-encoded small RNA and furthers our knowledge of the role of
      microRNAs in the cell response to viral infection.

PMID- 29046452
TI  - Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in
      genome packaging.
AB  - Non-enveloped viruses protect their genomes by packaging them into an outer shell
      or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses
      can involve interactions between capsid proteins and secondary structures in the
      viral genome as exemplified by the RNA bacteriophage MS2 and as proposed for
      other RNA viruses of plants, animals and human. In the picornavirus family of non
      enveloped RNA viruses, the requirements for genome packaging remain poorly
      understood. Here we show a novel and simple approach to identify predicted RNA
      secondary structures involved in genome packaging in the picornavirus foot-and
      mouth disease virus (FMDV). By interrogating deep sequencing data generated from
      both packaged and unpackaged populations of RNA we have determined multiple
      regions of the genome with constrained variation in the packaged population.
      Predicted secondary structures of these regions revealed stem loops with
      conservation of structure and a common motif at the loop. Disruption of these
      features resulted in attenuation of virus growth in cell culture due to a
      reduction in assembly of mature virions. This study provides evidence for the
      involvement of predicted RNA structures in picornavirus packaging and offers a
      readily transferable methodology for identifying packaging requirements in many
      other viruses.Importance In order to transmit their genetic material to a new
      host, non-enveloped viruses must protect their genomes by packaging them into an
      outer shell or capsid of virus-encoded proteins. For many non-enveloped RNA
      viruses the requirements for this critical part of the viral life cycle remain
      poorly understood. We have identified RNA sequences involved in genome packaging
      of the picornavirus foot-and-mouth disease virus. This virus causes an
      economically devastating disease of livestock affecting both the developed and
      developing world. The experimental methods developed to carry out this work are
      novel, simple and transferable to the study of packaging signals in other RNA
      viruses. Improved understanding of RNA packaging may lead to novel vaccine
      approaches or targets for antiviral drugs with broad spectrum activity.

PMID- 29046451
TI  - Mutations in the Influenza A Virus M1 Protein Enhance Virus Budding To Complement
      Lethal Mutations in the M2 Cytoplasmic Tail.
AB  - The influenza A virus M1 and M2 proteins play important roles in virus assembly
      and in the morphology of virus particles. Mutations in the distal cytoplasmic
      tail region of M2, and in particular a tyrosine-to-alanine mutation at residue 76
      (Y76A), were essential for infectious virus production and filament formation
      while having limited effects on total virus particle budding. Using a novel
      selection method, mutations at seven different M1 amino acids (residue 73, 94,
      135, 136, or 138 or a double mutation, 93/244) that are not found in circulating
      influenza virus strains or have not been previously identified to play a role in
      influenza A virus assembly were found to complement the lethal M2Y76A mutation.
      These M1 suppressor mutations restored infectious virus production in the
      presence of M2Y76A and mediated increased budding and filament formation even in
      the absence of M2. However, the efficiency of infectious virus replication was
      still dependent on the presence of the distal region of the M2 cytoplasmic tail.
      The data suggest that influenza A virus budding and genome incorporation can
      occur independently and provide further support for complementary roles of the M1
      and M2 proteins in virus assembly.IMPORTANCE Influenza virus particle assembly
      involves the careful coordination of various viral and host factors to optimally
      produce infectious virus particles. We have previously identified a mutation at
      position 76 of the influenza A virus M2 protein that drastically reduces
      infectious virus production and filament formation with minimal effects on virus
      budding. In this work, we identified suppressor mutations in the M1 protein which
      complement this lethal M2 mutation by increasing the efficiency with which virus
      particles bud from infected cells and restoring filament formation at the
      infected-cell surface. M2 distal cytoplasmic domain sequences were still required
      for optimal infectivity. This indicates that M1 and M2 can functionally replace
      each other in some, but not all, aspects of virus particle assembly.

PMID- 29046453
TI  - Murine Hepatitis Virus nsp14 Exoribonuclease Activity Is Required for Resistance
      to Innate Immunity.
AB  - Coronaviruses (CoVs) are positive-sense RNA viruses that infect numerous
      mammalian and avian species and are capable of causing severe and lethal disease
      in humans. CoVs encode several innate immune antagonists that counteract the host
      innate immune response to facilitate efficient viral replication. CoV
      nonstructural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity
      (ExoN), which performs a proofreading function and is required for high-fidelity
      replication. Outside of the order Nidovirales, arenaviruses are the only RNA
      viruses that encode an ExoN, which functions to degrade double-stranded RNA
      (dsRNA) replication intermediates. In this study, we tested the hypothesis that
      CoV ExoN also functions to antagonize the innate immune response. We demonstrate
      that viruses lacking ExoN activity [ExoN(-)] are sensitive to cellular
      pretreatment with interferon beta (IFN-beta) in a dose-dependent manner. In
      addition, ExoN(-) virus replication was attenuated in wild-type bone marrow
      derived macrophages (BMMs) and partially restored in interferon alpha/beta
      receptor-deficient (IFNAR-/-) BMMs. ExoN(-) virus replication did not result in
      IFN-beta gene expression, and in the presence of an IFN-beta-mediated antiviral
      state, ExoN(-) viral RNA levels were not substantially reduced relative to those
      of untreated samples. However, ExoN(-) virus generated from IFN-beta-pretreated
      cells had reduced specific infectivity and decreased relative fitness, suggesting
      that ExoN(-) virus generated during an antiviral state is less viable to
      establish a subsequent infection. Overall, our data suggest murine hepatitis
      virus (MHV) ExoN activity is required for resistance to the innate immune
      response, and antiviral mechanisms affecting the viral RNA sequence and/or an RNA
      modification act on viruses lacking ExoN activity.IMPORTANCE CoVs encode multiple
      antagonists that prevent or disrupt an efficient innate immune response.
      Additionally, no specific antiviral therapies or vaccines currently exist for
      human CoV infections. Therefore, the study of CoV innate immune antagonists is
      essential for understanding how CoVs overcome host defenses and to maximize
      potential therapeutic interventions. Here, we sought to determine the
      contributions of nsp14 ExoN activity in the induction of and resistance to the
      innate immune response. We show that viruses lacking nsp14 ExoN activity are more
      sensitive than wild-type MHV to restriction by exogenous IFN-beta and that
      viruses produced in the presence of an antiviral state are less capable of
      establishing a subsequent viral infection. Our results support the hypothesis
      that murine hepatitis virus ExoN activity is required for resistance to the
      innate immune response.

PMID- 29046454
TI  - Mechanisms of HERV-K (HML-2) Transcription during Human Mammary Epithelial Cell
      Transformation.
AB  - Increasing evidence suggests that repetitive elements may play a role in host
      gene regulation, particularly through the donation of alternative promoters,
      enhancers, splice sites, and termination signals. Elevated transcript expression
      of the endogenous retrovirus group HERV-K (HML-2) is seen in many human cancers,
      although the identities of the individual proviral loci contributing to this
      expression as well as their mechanisms of activation have been unclear. Using
      high-throughput next-generation sequencing techniques optimized for the capture
      of HML-2 expression, we characterized the HML-2 transcriptome and means of
      activation in an in vitro model of human mammary epithelial cell transformation.
      Our analysis showed significant expression originating from 15 HML-2 full-length
      proviruses, through four modes of transcription. The majority of expression was
      in the antisense orientation and from proviruses integrated within introns. We
      found two instances of long terminal repeat (LTR)-driven provirus transcription
      but no evidence to suggest that these active 5' LTRs were influencing nearby host
      gene expression. Importantly, LTR-driven transcription was restricted to
      tumorigenic cells, suggesting that LTR promoter activity is dependent upon the
      transcriptional environment of a malignant cell.IMPORTANCE Here, we use an in
      vitro model of human mammary epithelial cell transformation to assess how
      malignancy-associated shifts in the transcriptional milieu of a cell may impact
      HML-2 activity. We found 15 proviruses to be significantly expressed through four
      different mechanisms, with the majority of transcripts being antisense copies of
      proviruses located within introns. We saw active 5' LTR use in tumorigenic cells
      only, suggesting that the cellular environment of a cancer cell is a critical
      component for induction of LTR promoter activity. These findings have
      implications for future studies investigating HML-2 as a target for immunotherapy
      or as a biomarker for disease.

PMID- 29046455
TI  - Extended Synaptotagmin 1 Interacts with Herpes Simplex Virus 1 Glycoprotein M and
      Negatively Modulates Virus-Induced Membrane Fusion.
AB  - Enveloped viruses typically encode their own fusion machinery to enter cells.
      Herpesviruses are unusual, as they fuse with a number of cellular compartments
      throughout their life cycles. As uncontrolled fusion of the host membranes should
      be avoided in these events, tight regulation of the viral fusion machinery is
      critical. While studying herpes simplex virus 1 (HSV-1) glycoprotein gM, we
      identified the cellular protein E-Syt1 (extended synaptotagmin 1) as an
      interaction partner. The interaction took place in both infected and transfected
      cells, suggesting other viral proteins were not required for the interaction.
      Most interestingly, E-Syt1 is a member of the synaptotagmin family of membrane
      fusion regulators. However, the protein is known to promote the tethering of the
      endoplasmic reticulum (ER) to the plasma membrane. We now show that E-Syt1, along
      with the related E-Syt3, negatively modulates viral release into the
      extracellular milieu, cell-to-cell viral spread, and viral entry, all processes
      that implicate membrane fusion events. Similarly, these E-Syt proteins impacted
      the formation of virus-induced syncytia. Altogether, these findings hint at the
      modulation of the viral fusion machinery by the E-Syt family of
      proteins.IMPORTANCE Viruses typically encode their own fusion apparatus to enable
      them to enter cells. For many viruses, this means a single fusogenic protein.
      However, herpesviruses are large entities that express several accessory viral
      proteins to regulate their fusogenic activity. The present study hints at the
      additional participation of cellular proteins in this process, suggesting the
      host can also modulate viral fusion to some extent. Hence E-Syt proteins 1 and 3
      seem to negatively modulate the different viral fusion events that take place
      during the HSV-1 life cycle. This could represent yet another innate immunity
      response to the virus.

PMID- 29046456
TI  - Viperin targets flavivirus virulence by inducing assembly of non-infectious
      capsid particles.
AB  - Efficient antiviral immunity requires interference with virus replication at
      multiple layers targeting diverse steps in the viral life cycle. Here we describe
      a novel flavivirus inhibition mechanism that results in interferon-mediated
      obstruction of tick-borne encephalitis virus particle assembly, and involves
      release of malfunctional membrane associated capsid (C) particles. This mechanism
      is controlled by the activity of the interferon-induced protein viperin, a broad
      spectrum antiviral interferon stimulated gene. Through analysis of the viperin
      interactome, we identified the Golgi Brefeldin A resistant guanine nucleotide
      exchange factor 1 (GBF1), as the cellular protein targeted by viperin. Viperin
      induced antiviral activity as well as C-particle release was stimulated by GBF1
      inhibition and knock down, and reduced by elevated levels of GBF1. Our results
      suggest that viperin targets flavivirus virulence by inducing the secretion of
      unproductive non-infectious virus particles, by a GBF1-dependent mechanism. This
      yet undescribed antiviral mechanism allows potential therapeutic
      intervention.Importance The interferon response can target viral infection on
      almost every level, however, very little is known about interference of
      flavivirus assembly. Here we show that interferon, through the action of viperin,
      can disturb assembly of tick-borne encephalitis virus. The viperin protein is
      highly induced after viral infection and exhibit broad-spectrum antiviral
      activity. However, the mechanism of action is still elusive and appear to vary
      between the different viruses, indicating that cellular targets utilized by
      several viruses might be involved. In this study we show that viperin induce
      capsid particle release by interacting and inhibiting the function of the
      cellular protein Golgi Brefeldin A resistant guanine nucleotide exchange factor 1
      (GBF1). GBF1 is a key protein in the cellular secretory pathway and essential in
      the life cycle of many viruses, also targeted by viperin, implicating GBF1 as a
      novel putative drug target.

PMID- 29046457
TI  - HIV-1 Infection of Primary CD4+ T Cells Regulates the Expression of Specific
      Human Endogenous Retrovirus HERV-K (HML-2) Elements.
AB  - Endogenous retroviruses (ERVs) occupy extensive regions of the human genome.
      Although many of these retroviral elements have lost their ability to replicate,
      those whose insertion took place more recently, such as the HML-2 group of HERV-K
      elements, still retain intact open reading frames and the capacity to produce
      certain viral RNA and/or proteins. Transcription of these ERVs is, however,
      tightly regulated by dedicated epigenetic control mechanisms. Nonetheless, it has
      been reported that some pathological states, such as viral infections and certain
      cancers, coincide with ERV expression, suggesting that transcriptional
      reawakening is possible. HML-2 elements are reportedly induced during HIV-1
      infection, but the conserved nature of these elements has, until recently,
      rendered their expression profiling problematic. Here, we provide comprehensive
      HERV-K HML-2 expression profiles specific for productively HIV-1-infected primary
      human CD4+ T cells. We combined enrichment of HIV-1 infected cells using a
      reporter virus expressing a surface reporter for gentle and efficient
      purification with long-read single-molecule real-time sequencing. We show that
      three HML-2 proviruses-6q25.1, 8q24.3, and 19q13.42-are upregulated on average
      between 3- and 5-fold in HIV-1-infected CD4+ T cells. One provirus, HML-2
      12q24.33, in contrast, was repressed in the presence of active HIV replication.
      In conclusion, this report identifies the HERV-K HML-2 loci whose expression
      profiles differ upon HIV-1 infection in primary human CD4+ T cells. These data
      will help pave the way for further studies on the influence of endogenous
      retroviruses on HIV-1 replication.IMPORTANCE Endogenous retroviruses inhabit big
      portions of our genome. Moreover, although they are mainly inert, some of the
      evolutionarily younger members maintain the ability to express both RNA and
      proteins. We have developed an approach using long-read single-molecule real-time
      (SMRT) sequencing that produces long reads that allow us to obtain detailed and
      accurate HERV-K HML-2 expression profiles. We applied this approach to study HERV
      K expression in the presence or absence of productive HIV-1 infection of primary
      human CD4+ T cells. In addition to using SMRT sequencing, our strategy also
      includes the magnetic selection of the infected cells so that levels of
      background expression due to uninfected cells are kept at a minimum. The results
      presented here provide a blueprint for in-depth studies of the interactions of
      the authentic upregulated HERV-K HML-2 elements and HIV-1.

PMID- 29046458
TI  - A Tyrosine-Based Trafficking Motif of the Tegument Protein pUL71 Is Crucial for
      Human Cytomegalovirus Secondary Envelopment.
AB  - The human cytomegalovirus (HCMV) tegument protein pUL71 is required for efficient
      secondary envelopment and accumulates at the Golgi compartment-derived viral
      assembly complex (vAC) during infection. Analysis of various C-terminally
      truncated pUL71 proteins fused to enhanced green fluorescent protein (eGFP)
      identified amino acids 23 to 34 as important determinants for its Golgi complex
      localization. Sequence analysis and mutational verification revealed the presence
      of an N-terminal tyrosine-based trafficking motif (YXXPhi) in pUL71. This led us
      to hypothesize a requirement of the YXXPhi motif for the function of pUL71 in
      infection. Mutation of both the tyrosine residue and the entire YXXPhi motif
      resulted in an altered distribution of mutant pUL71 at the plasma membrane and in
      the cytoplasm during infection. Both YXXPhi mutant viruses exhibited similarly
      decreased focal growth and reduced virus yields in supernatants.
      Ultrastructurally, mutant-virus-infected cells exhibited impaired secondary
      envelopment manifested by accumulations of capsids undergoing an envelopment
      process. Additionally, clusters of capsid accumulations surrounding the vAC were
      observed, similar to the ultrastructural phenotype of a UL71-deficient mutant.
      The importance of endocytosis and thus the YXXPhi motif for targeting pUL71 to
      the Golgi complex was further demonstrated when clathrin-mediated endocytosis was
      inhibited either by coexpression of the C-terminal part of cellular AP180 (AP180
      C) or by treatment with methyl-beta-cyclodextrin. Both conditions resulted in a
      plasma membrane accumulation of pUL71. Altogether, these data reveal the presence
      of a functional N-terminal endocytosis motif that is an important determinant for
      intracellular localization of pUL71 and that is furthermore required for the
      function of pUL71 during secondary envelopment of HCMV capsids at the
      vAC.IMPORTANCE Human cytomegalovirus (HCMV) is the leading cause of birth defects
      among congenital virus infections and can lead to life-threatening infections in
      immunocompromised hosts. Current antiviral treatments target viral genome
      replication and are increasingly overcome by viral mutations. Therefore,
      identifying new targets for antiviral therapy is important for future development
      of novel treatment options. A detailed molecular understanding of the complex
      virus morphogenesis will identify potential viral as well as cellular targets for
      antiviral intervention. Secondary envelopment is an important viral process
      through which infectious virus particles are generated and which involves the
      action of several viral proteins, such as tegument protein pUL71. Targeting of
      pUL71 to the site of secondary envelopment appears to be crucial for its function
      during this process and is regulated by utilizing host trafficking mechanisms
      that are commonly exploited by viral glycoproteins. Thus, intracellular
      trafficking, if targeted, might present a novel target for antiviral therapy.

PMID- 29046459
TI  - Hepatitis C Virus Replication Depends on Endosomal Cholesterol Homeostasis.
AB  - Similar to other positive-strand RNA viruses, hepatitis C virus (HCV) causes
      massive rearrangements of intracellular membranes, resulting in a membranous web
      (MW) composed of predominantly double-membrane vesicles (DMVs), the presumed
      sites of RNA replication. DMVs are enriched for cholesterol, but mechanistic
      details on the source and recruitment of cholesterol to the viral replication
      organelle are only partially known. Here we focused on selected lipid transfer
      proteins implicated in direct lipid transfer at various endoplasmic reticulum
      (ER)-membrane contact sites. RNA interference (RNAi)-mediated knockdown
      identified several hitherto unknown HCV dependency factors, such as steroidogenic
      acute regulatory protein-related lipid transfer domain protein 3 (STARD3),
      oxysterol-binding protein-related protein 1A and -B (OSBPL1A and -B), and Niemann
      Pick-type C1 (NPC1), all residing at late endosome and lysosome membranes and
      required for efficient HCV RNA replication but not for replication of the closely
      related dengue virus. Focusing on NPC1, we found that knockdown or
      pharmacological inhibition caused cholesterol entrapment in lysosomal vesicles
      concomitant with decreased cholesterol abundance at sites containing the viral
      replicase factor NS5A. In untreated HCV-infected cells, unesterified cholesterol
      accumulated at the perinuclear region, partially colocalizing with NS5A at DMVs,
      arguing for NPC1-mediated endosomal cholesterol transport to the viral
      replication organelle. Consistent with cholesterol being an important structural
      component of DMVs, reducing NPC1-dependent endosomal cholesterol transport
      impaired MW integrity. This suggests that HCV usurps lipid transfer proteins,
      such as NPC1, at ER-late endosome/lysosome membrane contact sites to recruit
      cholesterol to the viral replication organelle, where it contributes to MW
      functionality.IMPORTANCE A key feature of the replication of positive-strand RNA
      viruses is the rearrangement of the host cell endomembrane system to produce a
      membranous replication organelle (RO). The underlying mechanisms are far from
      being elucidated fully. In this report, we provide evidence that HCV RNA
      replication depends on functional lipid transport along the endosomal-lysosomal
      pathway that is mediated by several lipid transfer proteins, such as the Niemann
      Pick type C1 (NPC1) protein. Pharmacological inhibition of NPC1 function reduced
      viral replication, impaired the transport of cholesterol to the viral replication
      organelle, and altered organelle morphology. Besides NPC1, our study reports the
      importance of additional endosomal and lysosomal lipid transfer proteins required
      for viral replication, thus contributing to our understanding of how HCV
      manipulates their function in order to generate a membranous replication
      organelle. These results might have implications for the biogenesis of
      replication organelles of other positive-strand RNA viruses.

PMID- 29046460
TI  - Myeloid Dendritic Cells Repress Human Cytomegalovirus Gene Expression and Spread
      by Releasing Interferon-Unrelated Soluble Antiviral Factors.
AB  - Cytomegalovirus (CMV) is a betaherpesvirus that latently infects most adult
      humans worldwide and is a major cause of morbidity and mortality in
      immunocompromised hosts. Latent human CMV (HCMV) is believed to reside in
      precursors of myeloid-lineage leukocytes and monocytes, which give rise to
      macrophages and dendritic cells (DC). We report here that human monocyte-derived
      DC (mo-DC) suppress HCMV infection in coculture with infected fibroblast target
      cells in a manner dependent on the effector-to-target ratio. Intriguingly,
      optimal activation of mo-DC was achieved under coculture conditions and not by
      direct infection with HCMV, implying that mo-DC may recognize unique molecular
      patterns on, or within, infected fibroblasts. We show that HCMV is controlled by
      secreted factors that act by priming defenses in target cells rather than by
      direct viral neutralization, but we excluded a role for interferons (IFNs) in
      this control. The expression of lytic viral genes in infected cells and the
      progression of infection were significantly slowed, but this effect was
      reversible, indicating that the control of infection depended on the transient
      induction of antiviral effector molecules in target cells. Using immediate early
      or late-phase reporter HCMVs, we show that soluble factors secreted in the
      cocultures suppress HCMV replication at both stages of the infection and that
      their antiviral effects are robust and comparable in numerous batches of mo-DC as
      well as in primary fibroblasts and stromal cells.IMPORTANCE Human cytomegalovirus
      is a widespread opportunistic pathogen that can cause severe disease and
      complications in vulnerable individuals. This includes newborn children, HIV AIDS
      patients, and transplant recipients. Although the majority of healthy humans
      carry this virus throughout their lives without symptoms, it is not exactly clear
      which tissues in the body are the main reservoirs of latent virus infection or
      how the delicate balance between the virus and the immune system is maintained
      over an individual's lifetime. Here, for the first time, we provide evidence for
      a novel mechanism of direct virus control by a subset of human innate immune
      cells called dendritic cells, which are regarded as a major site of virus latency
      and reactivation. Our findings may have important implications in HCMV disease
      prevention as well as in development of novel therapeutic approaches.

PMID- 29046461
TI  - Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella
      Zoster Virus Lytic Infection.
AB  - Varicella-zoster virus (VZV) is highly cell associated when grown in culture and
      has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in
      vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in
      vivo by airborne transmission. Neurons are major targets for VZV in vivo; in
      neurons, the virus can establish latency and reactivate to produce infectious
      virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free
      wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more
      permissive for WT VZV infection than very-early-passage human embryonic lung
      cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production
      or virus isolation. The peak titers achieved after infection were ~10-fold higher
      in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU
      ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells.
      Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other
      herpesviruses; instead, the cells previously used to propagate virus in vitro may
      have been suboptimal. Furthermore, based on electron microscopy, neurons infected
      with VZV produced fewer defective or incomplete viral particles than MRC-5 cells.
      Our data suggest that neurons derived from hESC may have advantages compared to
      other cells for studies of VZV pathogenesis, for obtaining stocks of virus with
      high titers, and for isolating VZV from clinical specimens.IMPORTANCE Varicella
      zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been
      difficult to obtain, both for in vitro studies and for vaccine production. While
      numerous cells lines have been tested for their ability to produce high titers of
      VZV, the number of total virus particles relative to the number of viral
      particles that can form plaques in culture has been reported to be extremely high
      relative to that in other viruses. We show that VZV grows to much higher titers
      in human neurons than in other cell types in vitro and that the number of total
      virus genomes relative to the number of viral particles that can form plaques in
      culture is much lower in human neurons than other cultured cells. These findings
      indicate that human neurons may be useful for studying VZV in vitro, for growing
      preparations of virus with high titers, and for isolating the virus from human
      samples.

PMID- 29046462
TI  - Distinct Roles of Cellular ESCRT-I and ESCRT-III Proteins in Efficient Entry and
      Egress of Budded Virions of Autographa californica Multiple Nucleopolyhedrovirus.
AB  - The endosomal sorting complex required for transport (ESCRT) machinery is
      necessary for budding of many enveloped viruses. Recently, it was demonstrated
      that Vps4, the key regulator for recycling of the ESCRT-III complex, is required
      for efficient infection by the baculovirus Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV). However, ESCRT assembly, regulation, and function
      are complex, and little is known regarding the details of participation of
      specific ESCRT complexes in AcMNPV infection. In this study, the core components
      of ESCRT-I (Tsg101 and Vps28) and ESCRT-III (Vps2B, Vps20, Vps24, Snf7, Vps46,
      and Vps60) were cloned from Spodoptera frugiperda Using a viral complementation
      system and RNA interference (RNAi) assays, we found that ESCRT-I and ESCRT-III
      complexes are required for efficient entry of AcMNPV into insect cells. In cells
      knocking down or overexpressing dominant negative (DN) forms of the components of
      ESCRT-I and ESCRT-III complexes, entering virions were partially trapped within
      the cytosol. To examine only egress, cells were transfected with the double
      stranded RNA (dsRNA) targeting an individual ESCRT-I or ESCRT-III gene and viral
      bacmid DNA or viral bacmid DNA that expressed DN forms of ESCRT-I and ESCRT-III
      components. We found that ESCRT-III components (but not ESCRT-I components) are
      required for efficient nuclear egress of progeny nucleocapsids. In addition, we
      found that several baculovirus core or conserved proteins (Ac11, Ac76, Ac78,
      GP41, Ac93, Ac103, Ac142, and Ac146) interact with Vps4 and components of ESCRT
      III. We propose that these viral proteins may form an "egress complex" that is
      involved in recruiting ESCRT-III components to a virus egress domain on the
      nuclear membrane.IMPORTANCE The ESCRT system is hijacked by many enveloped
      viruses to mediate budding and release. Recently, it was found that Vps4, the key
      regulator of the cellular ESCRT machinery, is necessary for efficient entry and
      egress of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). However,
      little is known about the roles of specific ESCRT complexes in AcMNPV infection.
      In this study, we demonstrated that ESCRT-I and ESCRT-III complexes are required
      for efficient entry of AcMNPV into insect cells. The components of ESCRT-III (but
      not ESCRT-I) are also necessary for efficient nuclear egress of progeny
      nucleocapsids. Several baculovirus core or conserved proteins were found to
      interact with Vps4 and components of ESCRT-III, and these interactions may
      suggest the formation of an "egress complex" involved in the nuclear release or
      transport of viral nucleocapsids.

PMID- 29046463
TI  - Flow Cytometric Detection of PrPSc in Neurons and Glial Cells from Prion-Infected
      Mouse Brains.
AB  - In prion diseases, an abnormal isoform of prion protein (PrPSc) accumulates in
      neurons, astrocytes, and microglia in the brains of animals affected by prions.
      Detailed analyses of PrPSc-positive neurons and glial cells are required to
      clarify their pathophysiological roles in the disease. Here, we report a novel
      method for the detection of PrPSc in neurons and glial cells from the brains of
      prion-infected mice by flow cytometry using PrPSc-specific staining with
      monoclonal antibody (MAb) 132. The combination of PrPSc staining and
      immunolabeling of neural cell markers clearly distinguished neurons, astrocytes,
      and microglia that were positive for PrPSc from those that were PrPSc negative.
      The flow cytometric analysis of PrPSc revealed the appearance of PrPSc-positive
      neurons, astrocytes, and microglia at 60 days after intracerebral prion
      inoculation, suggesting the presence of PrPSc in the glial cells, as well as in
      neurons, from an early stage of infection. Moreover, the kinetic analysis of
      PrPSc revealed a continuous increase in the proportion of PrPSc-positive cells
      for all cell types with disease progression. Finally, we applied this method to
      isolate neurons, astrocytes, and microglia positive for PrPSc from a prion
      infected mouse brain by florescence-activated cell sorting. The method described
      here enables comprehensive analyses specific to PrPSc-positive neurons,
      astrocytes, and microglia that will contribute to the understanding of the
      pathophysiological roles of neurons and glial cells in PrPSc-associated
      pathogenesis.IMPORTANCE Although formation of PrPSc in neurons is associated
      closely with neurodegeneration in prion diseases, the mechanism of
      neurodegeneration is not understood completely. On the other hand, recent studies
      proposed the important roles of glial cells in PrPSc-associated pathogenesis,
      such as the intracerebral spread of PrPSc and clearance of PrPSc from the brain.
      Despite the great need for detailed analyses of PrPSc-positive neurons and glial
      cells, methods available for cell type-specific analysis of PrPSc have been
      limited thus far to microscopic observations. Here, we have established a novel
      high-throughput method for flow cytometric detection of PrPSc in cells with more
      accurate quantitative performance. By applying this method, we succeeded in
      isolating PrPSc-positive cells from the prion-infected mouse brains via
      fluorescence-activated cell sorting. This allows us to perform further detailed
      analysis specific to PrPSc-positive neurons and glial cells for the clarification
      of pathological changes in neurons and pathophysiological roles of glial cells.

PMID- 29046465
TI  - [Usefulness of Bilateral rSO<sub>2</sub> Monitoring for Predicting Cerebral
      Hyperperfusion Syndrome after Carotid Artery Stenting].
AB  - OBJECTIVE: Cerebral hyperperfusion syndrome(CHS)and cerebral hyperperfusion
      phenomenon(CHP)induce intracranial hemorrhage and can become critical
      complications after carotid artery stenting(CAS). The purpose of the present
      study was to predict and avoid CHS after CAS using bilateral rSO<sub>2</sub>
      intraoperative monitoring. METHODS: We retrospectively analyzed 100 consecutive
      patients who underwent CAS between January 2012 and May 2014 in our institution.
      We performed continuous bilateral rSO<sub>2</sub> monitoring from anesthetic
      induction to the day following CAS. CHS was defined as the deterioration of
      neurological conditions post-CAS, no ischemic changes on post-CAS head CT or
      brain MRI, an increase in cerebral blood flow(CBF)and cerebral blood volume(CBV),
      and shortening of the mean transit time(MTT)or time to peak(TTP)on CT perfusion.
      To compare the CHS/CHP group and non-CHS/CHP group, we defined four
      parameters:rSO<sub>2</sub> difference(rSO<sub>2</sub> at the endpoint of the
      procedure-baseline rSO<sub>2</sub>), DeltarSO<sub>2</sub> difference(affected
      side rSO<sub>2</sub> difference-unaffected side rSO<sub>2</sub> difference),
      rSO<sub>2</sub> ratio(rSO<sub>2</sub> at the endpoint of the procedure/baseline
      rSO<sub>2</sub>), and DeltarSO<sub>2</sub> ratio(affected side rSO<sub>2</sub>
      ratio/unaffected side rSO<sub>2</sub> ratio). RESULTS: There were 2 CHS
      cases(2.2%)and 3 CHP cases(3.3%). In the CHS/CHP group, the DeltarSO<sub>2</sub>
      difference and DeltarSO<sub>2</sub> ratio were significantly higher than those in
      the non-CHS/CHP group(p value<0.05);however, no significant differences were
      found in the affected side rSO<sub>2</sub> difference(p value=0.063)and affected
      side rSO<sub>2</sub> ratio(p value=0.054)between the groups. CONCLUSION: We could
      promptly detect CHS and CHP in all cases by using continuous bilateral
      rSO<sub>2</sub> monitoring and analysis of the DeltarSO<sub>2</sub> difference
      and DeltarSO<sub>2</sub> ratio.

PMID- 29046466
TI  - [Five Cases of Neuroendovascular Treatment Using the Goose Neck Snare for
      Inducing and Holding the Guiding Catheter].
AB  - The stabilization of a guiding catheter is a very important factor for successful
      endovascular treatment. However, it is sometimes difficult to obtain sufficient
      stabilization because of the tortuosity of the approach route. A Goose Neck Snare
      is useful for the retrieval of intravascular foreign bodies and can be used to
      hold the guiding catheter. We describe five cases of endovascular treatment
      performed while using the Goose Neck Snare via the brachial artery to hold the
      guiding catheter. We discuss the utility of this strategy.

PMID- 29046464
TI  - Screening for Neuraminidase Inhibitor Resistance Markers among Avian Influenza
      Viruses of the N4, N5, N6, and N8 Neuraminidase Subtypes.
AB  - Several subtypes of avian influenza viruses (AIVs) are emerging as novel human
      pathogens, and the frequency of related infections has increased in recent years.
      Although neuraminidase (NA) inhibitors (NAIs) are the only class of antiviral
      drugs available for therapeutic intervention for AIV-infected patients, studies
      on NAI resistance among AIVs have been limited, and markers of resistance are
      poorly understood. Previously, we identified unique NAI resistance substitutions
      in AIVs of the N3, N7, and N9 NA subtypes. Here, we report profiles of NA
      substitutions that confer NAI resistance in AIVs of the N4, N5, N6, and N8 NA
      subtypes using gene-fragmented random mutagenesis. We generated libraries of
      mutant influenza viruses using reverse genetics (RG) and selected resistant
      variants in the presence of the NAIs oseltamivir carboxylate and zanamivir in
      MDCK cells. In addition, two substitutions, H274Y and R292K (N2 numbering), were
      introduced into each NA gene for comparison. We identified 37 amino acid
      substitutions within the NA gene, 16 of which (4 in N4, 4 in N5, 4 in N6, and 4
      in N8) conferred resistance to NAIs (oseltamivir carboxylate, zanamivir, or
      peramivir) as determined using a fluorescence-based NA inhibition assay.
      Substitutions conferring NAI resistance were mainly categorized as either novel
      NA subtype specific (G/N147V/I, A246V, and I427L) or previously reported in other
      subtypes (E119A/D/V, Q136K, E276D, R292K, and R371K). Our results demonstrate
      that each NA subtype possesses unique NAI resistance markers, and knowledge of
      these substitutions in AIVs is important in facilitating antiviral susceptibility
      monitoring of NAI resistance in AIVs.IMPORTANCE The frequency of human infections
      with avian influenza viruses (AIVs) has increased in recent years. Despite the
      availability of vaccines, neuraminidase inhibitors (NAIs), as the only available
      class of drugs for AIVs in humans, have been constantly used for treatment,
      leading to the inevitable emergence of drug-resistant variants. To screen for
      substitutions conferring NAI resistance in AIVs of N4, N5, N6, and N8 NA
      subtypes, random mutations within the target gene were generated, and resistant
      viruses were selected from mutant libraries in the presence of individual drugs.
      We identified 16 NA substitutions conferring NAI resistance in the tested AIV
      subtypes; some are novel and subtype specific, and others have been previously
      reported in other subtypes. Our findings will contribute to an increased and more
      comprehensive understanding of the mechanisms of NAI-induced inhibition of
      influenza virus and help lead to the development of drugs that bind to
      alternative interaction motifs.

PMID- 29046467
TI  - [Clinical Characteristics of Craniocervical Junction Arteriovenous Fistulas].
AB  - OBJECTIVE: Craniocervical junction arteriovenous fistulas(CCJ-AVFs)are extremely
      rare lesions that may result in both subarachnoid hemorrhage(SAH)and myelopathy.
      Diagnosis of CCJ-AVF is difficult and may be delayed due to variable clinical
      features and a spectrum of neuroradiological findings. To elucidate the clinical
      characteristics of CCJ-AVF, we analyzed the clinical symptoms, neuroimaging
      findings, and the results of surgical treatment in five patients. RESULTS: Among
      the five patients, four were diagnosed with dural AVFs, and the remaining patient
      was diagnosed with radicular AVF. Two of the five patients presented with SAH,
      and the rest presented with myelopathy. In both the SAH patients, the initial
      digital subtraction angiography(DSA)failed to reveal the AVFs, and a definitive
      diagnosis was made only after repeated DSAs. In two of the three myelopathy
      patients, the diagnosis was delayed because of nonspecific chronic neurological
      symptoms which resembled a thoracolumbar lesion. Four patients underwent shunt
      occlusion through direct surgery and demonstrated favorable outcomes. One
      myelopathy patient, however, demonstrated abrupt onset, associated with
      progressive neurological deterioration, which resulted in poor prognosis. The
      magnetic resonance imaging(MRI)findings, which included intramedullary high
      intensity on a T2 weighted image, flow void, and varix at the cervical cord, were
      specific for the myelopathy patients. CONCLUSION: A thorough 4-vessel DSA study,
      including the cervical region, is mandatory for SAH patients whose clots are
      predominantly in the posterior fossa, and repeated DSA must be considered in
      cases of unknown origin. CCJ-AVF may cause myelopathy, with symptoms such as
      urinary dysfunction and/or paraparesis. Screening with a cervical MRI is useful
      for detecting CCJ-AVF in cases of myelopathy. Emergency radical treatment must be
      attempted for those patients demonstrating abrupt onset associated with symptoms
      of progressive deterioration, such as respiratory dysfunction or bulbar palsy.

PMID- 29046468
TI  - [A Case of Dural Arteriovenous Fistula that Developed 21 Months after Cerebral
      Venous Sinus Thrombosis].
AB  - A 56-year-old man experienced a sudden onset of left hemiparesis. The computed
      tomography(CT)scan revealed a lobar hemorrhage in the right fronto-parietal lobe.
      After his admission, deep vein thrombosis was detected in his left lower limb,
      and angiograms taken on the 36th day of hospitalization revealed cerebral venous
      sinus thrombosis. Anticoagulant treatment was induced. After 21 months, he
      experienced a sudden onset of left hemiparesis again. The CT scan revealed a new
      lobar hemorrhage in the right frontal lobe, and angiograms revealed that two
      dural arteriovenous fistulas(dAVF)developed in the superior sagittal
      sinus(SSS)and the left transverse-sigmoid sinus. The one in the SSS had
      retrograde drainage from the bilateral middle meningeal artery, and we performed
      transarterial embolization with 50% n-butyl-cyanoacrylate. Postoperative course
      was uneventful and no further stroke occurred. Intracranial dAVF is known to be
      an acquired disease caused by venous hypertension, but we rarely find new
      development of dAVFs after venous diseases. This patient's case will help to
      elucidate the pathophysiology of dAVF.

PMID- 29046469
TI  - [A Rare Case of Ruptured/Unruptured Miniature Aneurysms Originating from the
      Infundibular Dilatation of the Callosomarginal Artery, Branching from the
      Infracallosal(A2)Segment of the Azygos Anterior Cerebral Artery].
AB  - We report the first case of two de novo miniature
      aneurysms(ruptured/unruptured)emerging from the infundibular dilatation(ID)of the
      callosomarginal artery, which branches from the infracallosal(A2)segment of the
      azygos anterior cerebral artery(AACA), in a 36-year-old woman. The patient had
      previously been diagnosed with a miniature, unruptured aneurysm, occurring in the
      A2 segment of the AACA, detected by CT angiography(CTA)at another hospital two
      years ago, and had been followed up with MR angiography(MRA)every 6 months. Three
      months after the final check-up with MRA, which did not indicate a significant
      change in the aneurysm, the patient presented with subarachnoid hemorrhage.
      Subsequent CTA and digital subtraction angiograms revealed that the right
      callosomarginal artery, originating from the apex of the aneurysmal bulge, had a
      maximal diameter of 3mm, indicating an ID of the artery. Additionally, two
      miniature bleb-like aneurysms emerged from the ID, projecting in opposite
      directions:one projecting to the right-posterior/superior direction and the other
      to the left-anterior/inferior direction. Both aneurysms were successfully clipped
      via a right pterional approach with partial resection of the gyrus rectus, and
      the right-projecting aneurysm was confirmed to be ruptured during surgery. In the
      current report, we review previously reported cases of AACA with aneurysms, and
      discuss their clinical characteristics, and the possible mechanisms underlying
      the formation of the ID and de novo aneurysms in this extremely rare case.

PMID- 29046470
TI  - [Metastasis of Hepatocellular Carcinoma to the Membrane of Chronic Subdural
      Hematomas:A Case Report].
AB  - An 81-year-old man presented with gait disturbance. Two months previously, he
      suffered from hepatocellular carcinoma and transarterial chemoembolization was
      performed. A head computed tomography(CT)scan revealed bilateral chronic subdural
      hematomas. The patient's gait disturbance was improved after achievement of
      bilateral burr hole drainage. A head CT two months after treatment revealed no
      recurrence of the hematomas. However, head CT images obtained four months after
      treatment revealed an abnormal mass in the right parietal region attached to the
      internal surface of the skull. The mass was located in the same region from where
      the chronic subdural hematomas were previously removed via burr hole drainage,
      and was suspected to have originated from the dura mater. We performed craniotomy
      and total removal of the mass. The dura mater was intact, and macroscopically,
      the mass originated from the organized membrane of the chronic subdural hematoma.
      A pathological examination revealed metastasis of hepatocellular carcinoma to the
      membrane of the chronic subdural hematomas. Head magnetic resonance
      imaging(MRI)performed 39 days after craniotomy presented a new lesion in the left
      parietal region attached to the internal surface of the skull. The patient
      subsequently died 46 days post-operation. When examining chronic subdural
      hematomas in cancer patients, histological examination of the dura mater,
      hematoma, and membrane of the hematoma are important. The possibility of
      metastasis to the capsule of the hematoma should be considered.

PMID- 29046471
TI  - [A Case Report of Congenital Protein C Deficiency with Cerebral Venous Sinus
      Thrombosis during Early Pregnancy Period].
AB  - A 35-year-old woman at eight weeks of gestation in her second pregnancy presented
      with generalized seizures. Magnetic resonance images revealed a small hemorrhagic
      infarction in the left frontal lobe, and magnetic resonance venography indicated
      cerebral venous sinus thrombosis. After hospitalization, anticoagulant therapy
      was continued, and a low protein C level was confirmed, which was also confirmed
      in both her mother and her sister. Follow-up magnetic resonance venography
      performed on day 27 confirmed that the cerebral venous sinuses had undergone
      recanalization. After a completed gestation period, the patient gave birth to
      healthy girl uneventfully.

PMID- 29046473
TI  - [Clinical Applications of Positron Emission Tomography for Neurosurgery(3)PET for
      Patients with Intractable Epilepsy].

PMID- 29046472
TI  - [Surgical Treatment of a Giant Olfactory Groove Schwannoma:A Case Report].
AB  - Schwannomas originating from the olfactory nerve are extremely rare because the
      olfactory nerve does not normally contain Schwann cells. We describe a case of a
      giant schwannoma of the olfactory groove. A 73-year-old woman presented with
      anosmia persisting for 10 months. Head computed tomography(CT)for head trauma at
      another hospital demonstrated a tumor lesion located in the left frontal lobe and
      paranasal sinus. She had never suffered epilepsy, and past medical history and
      family history identified no indicators. Neurological examination revealed
      anosmia and dementia. Head CT demonstrated a tumor lesion with bone erosion,
      causing a defect of about 5cm in the frontal base. Head magnetic
      resonance(MR)imaging with contrast medium indicated a lesion that was 6cm in
      diameter, with heterogeneous enhancement and severe perifocal edema in the left
      frontal base, extending into the paranasal cavity. The tumor was resected through
      a left extradural subfrontal approach with bicoronal frontal craniotomy. The
      endoscopic approach was also performed simultaneously to remove the tumor in the
      paranasal sinus. The cystic tumor was soft and easy to bleed. Intraoperatively
      the right olfactory nerve was confirmed, but the left olfactory nerve could not
      be identified because of replacement by the tumor, suggesting that the tumor had
      originated from the left olfactory nerve. The defect of the dura was repaired
      with femoral fascia, the pedunculated periosteal flap was laid over the frontal
      base, and the bone defect was repaired with the inner plate of the frontal
      calvaria. Postoperative head MR imaging with contrast medium revealed no residual
      lesion. The patient was discharged 25 days after surgery, without new
      neurological deficits. Histological examination identified mixed Antoni type A
      and Antoni type B schwannoma on hematoxylin and eosin staining and S-100 protein
      on immunostaining.

PMID- 29046474
TI  - Human alternative Klotho mRNA is a nonsense-mediated mRNA decay target
      inefficiently spliced in renal disease.
AB  - Klotho is a renal protein involved in phosphate homeostasis, which is
      downregulated in renal disease. It has long been considered an antiaging factor.
      Two Klotho gene transcripts are thought to encode membrane-bound and secreted
      Klotho. Indeed, soluble Klotho is detectable in bodily fluids, but the relative
      contributions of Klotho secretion and of membrane-bound Klotho shedding are
      unknown. Recent advances in RNA surveillance reveal that premature termination
      codons, as present in alternative Klotho mRNA (for secreted Klotho), prime mRNAs
      for degradation by nonsense-mediated mRNA decay (NMD). Disruption of NMD led to
      accumulation of alternative Klotho mRNA, indicative of normally continuous
      degradation. RNA IP for NMD core factor UPF1 resulted in enrichment for
      alternative Klotho mRNA, which was also not associated with polysomes, indicating
      no active protein translation. Alternative Klotho mRNA transcripts colocalized
      with some P bodies, where NMD transcripts are degraded. Moreover, we could not
      detect secreted Klotho in vitro. These results suggest that soluble Klotho is
      likely cleaved membrane-bound Klotho only. Furthermore, we found that, especially
      in acute kidney injury, splicing of the 2 mRNA transcripts is dysregulated, which
      was recapitulated by various noxious stimuli in vitro. This likely constitutes a
      novel mechanism resulting in the downregulation of membrane-bound Klotho.

PMID- 29046475
TI  - Evidence for mast cells contributing to neuromuscular pathology in an inherited
      model of ALS.
AB  - Evidence indicates that neuroinflammation contributes to motor neuron
      degeneration in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative
      disease leading to progressive muscular paralysis. However, it remains elusive
      whether inflammatory cells can interact with degenerating distal motor axons,
      influencing the progressive denervation of neuromuscular junctions (NMJs). By
      analyzing the muscle extensor digitorum longus (EDL) following paralysis onset in
      the SOD1G93A rat model, we have observed a massive infiltration and degranulation
      of mast cells, starting after paralysis onset and correlating with progressive
      NMJ denervation. Remarkably, mast cells accumulated around degenerating motor
      axons and NMJs, and were also associated with macrophages. Mast cell accumulation
      and degranulation in paralytic EDL muscle was prevented by systemic treatment
      over 15 days with masitinib, a tyrosine kinase inhibitor currently in clinical
      trials for ALS exhibiting pharmacological activity affecting mast cells and
      microglia. Masitinib-induced mast cell reduction resulted in a 35% decrease in
      NMJ denervation and reduced motor deficits as compared with vehicle-treated rats.
      Masitinib also normalized macrophage infiltration, as well as regressive changes
      in Schwann cells and capillary networks observed in advanced paralysis. These
      findings provide evidence for mast cell contribution to distal axonopathy and
      paralysis progression in ALS, a mechanism that can be therapeutically targeted by
      masitinib.

PMID- 29046476
TI  - Tracking mesenchymal stem cell contributions to regeneration in an
      immunocompetent cartilage regeneration model.
AB  - It is currently controversially discussed whether mesenchymal stem cells (MSC)
      facilitate cartilage regeneration in vivo by a progenitor- or a nonprogenitor
      mediated mechanism. Here, we describe a potentially novel unbiased in vivo cell
      tracking system based on transgenic donor and corresponding immunocompetent
      marker-tolerant recipient mouse and rat lines in inbred genetic backgrounds.
      Tolerance of recipients was achieved by transgenic expression of an
      immunologically neutral but physicochemically distinguishable variant of the
      marker human placental alkaline phosphatase (ALPP). In this dual transgenic
      system, donor lines ubiquitously express WT, heat-resistant ALPP protein, whereas
      recipient lines express a heat-labile ALPP mutant (ALPPE451G) resulting from a
      single amino acid substitution. Tolerance of recipient lines to ALPP-expressing
      cells and tissues was verified by skin transplantation. Using this model, we show
      that intraarticularly injected MSC contribute to regeneration of articular
      cartilage in full-thickness cartilage defects mainly via a nonprogenitor-mediated
      mechanism.

PMID- 29046477
TI  - Increased putamen hypercapnic vasoreactivity in levodopa-induced dyskinesia.
AB  - In a rodent model of Parkinson's disease (PD), levodopa-induced involuntary
      movements have been linked to striatal angiogenesis - a process that is difficult
      to document in living human subjects. Angiogenesis can be accompanied by
      localized increases in cerebral blood flow (CBF) responses to hypercapnia. We
      therefore explored the possibility that, in the absence of levodopa, local
      hypercapnic CBF responses are abnormally increased in PD patients with levodopa
      induced dyskinesias (LID) but not in their nondyskinetic (NLID) counterparts. We
      used H215O PET to scan 24 unmedicated PD subjects (12 LID and 12 NLID) and 12
      matched healthy subjects in the rest state under normocapnic and hypercapnic
      conditions. Hypercapnic CBF responses were compared to corresponding levodopa
      responses from the same subjects. Group differences in hypercapnic vasoreactivity
      were significant only in the posterior putamen, with greater CBF responses in LID
      subjects compared with the other subjects. Hypercapnic and levodopa-mediated CBF
      responses measured in this region exhibited distinct associations with disease
      severity: the former correlated with off-state motor disability ratings but not
      symptom duration, whereas the latter correlated with symptom duration but not
      motor disability. These are the first in vivo human findings linking LID to
      microvascular changes in the basal ganglia.

PMID- 29046478
TI  - Cinacalcet corrects hypercalcemia in mice with an inactivating Galpha11 mutation.
AB  - Loss-of-function mutations of GNA11, which encodes G-protein subunit alpha11
      (Galpha11), a signaling partner for the calcium-sensing receptor (CaSR), result
      in familial hypocalciuric hypercalcemia type 2 (FHH2). FHH2 is characterized by
      hypercalcemia, inappropriately normal or raised parathyroid hormone (PTH)
      concentrations, and normal or low urinary calcium excretion. A mouse model for
      FHH2 that would facilitate investigations of the in vivo role of Galpha11 and the
      evaluation of calcimimetic drugs, which are CaSR allosteric activators, is not
      available. We therefore screened DNA from > 10,000 mice treated with the chemical
      mutagen N-ethyl-N-nitrosourea (ENU) for GNA11 mutations and identified a Galpha11
      variant, Asp195Gly (D195G), which downregulated CaSR-mediated intracellular
      calcium signaling in vitro, consistent with it being a loss-of-function mutation.
      Treatment with the calcimimetic cinacalcet rectified these signaling responses.
      In vivo studies showed mutant heterozygous (Gna11+/195G) and homozygous
      (Gna11195G/195G) mice to be hypercalcemic with normal or increased plasma PTH
      concentrations and normal urinary calcium excretion. Cinacalcet (30mg/kg orally)
      significantly reduced plasma albumin-adjusted calcium and PTH concentrations in
      Gna11+/195G and Gna11195G/195G mice. Thus, our studies have established a mouse
      model with a germline loss-of-function Galpha11 mutation that is representative
      for FHH2 in humans and demonstrated that cinacalcet can correct the associated
      abnormalities of plasma calcium and PTH.

PMID- 29046479
TI  - Lipoprotein lipase reaches the capillary lumen in chickens despite an apparent
      absence of GPIHBP1.
AB  - In mammals, GPIHBP1 is absolutely essential for transporting lipoprotein lipase
      (LPL) to the lumen of capillaries, where it hydrolyzes the triglycerides in
      triglyceride-rich lipoproteins. In all lower vertebrate species (e.g., birds,
      amphibians, reptiles, fish), a gene for LPL can be found easily, but a gene for
      GPIHBP1 has never been found. The obvious question is whether the LPL in lower
      vertebrates is able to reach the capillary lumen. Using purified antibodies
      against chicken LPL, we showed that LPL is present on capillary endothelial cells
      of chicken heart and adipose tissue, colocalizing with von Willebrand factor.
      When the antibodies against chicken LPL were injected intravenously into
      chickens, they bound to LPL on the luminal surface of capillaries in heart and
      adipose tissue. LPL was released rapidly from chicken hearts with an infusion of
      heparin, consistent with LPL being located inside blood vessels. Remarkably,
      chicken LPL bound in a specific fashion to mammalian GPIHBP1. However, we could
      not identify a gene for GPIHBP1 in the chicken genome, nor could we identify a
      transcript for GPIHBP1 in a large chicken RNA-seq data set. We conclude that LPL
      reaches the capillary lumen in chickens - as it does in mammals - despite an
      apparent absence of GPIHBP1.

PMID- 29046480
TI  - Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital
      heart disease.
AB  - Birth defects are the leading cause of infant mortality, and they are caused by a
      combination of genetic and environmental factors. Environmental risk factors may
      contribute to birth defects in genetically susceptible infants by altering
      critical molecular pathways during embryogenesis, but experimental evidence for
      gene-environment interactions is limited. Fetal hyperglycemia associated with
      maternal diabetes results in a 5-fold increased risk of congenital heart disease
      (CHD), but the molecular basis for this correlation is unknown. Here, we show
      that the effects of maternal hyperglycemia on cardiac development are sensitized
      by haploinsufficiency of Notch1, a key transcriptional regulator known to cause
      CHD. Using ATAC-seq, we found that hyperglycemia decreased chromatin
      accessibility at the endothelial NO synthase (Nos3) locus, resulting in reduced
      NO synthesis. Transcription of Jarid2, a regulator of histone methyltransferase
      complexes, was increased in response to reduced NO, and this upregulation
      directly resulted in inhibition of Notch1 expression to levels below a threshold
      necessary for normal heart development. We extended these findings using a
      Drosophila maternal diabetic model that revealed the evolutionary conservation of
      this interaction and the Jarid2-mediated mechanism. These findings identify a
      gene-environment interaction between maternal hyperglycemia and Notch signaling
      and support a model in which environmental factors cause birth defects in
      genetically susceptible infants.

PMID- 29046481
TI  - Reevaluation of immune activation in the era of cART and an aging HIV-infected
      population.
AB  - Biological aging is associated with immune activation (IA) and declining immunity
      due to systemic inflammation. It is widely accepted that HIV infection causes
      persistent IA and premature immune senescence despite effective antiretroviral
      therapy and virologic suppression; however, the effects of combined HIV infection
      and aging are not well defined. Here, we assessed the relationship between
      markers of IA and inflammation during biological aging in HIV-infected and 
      uninfected populations. Antibody response to seasonal influenza vaccination was
      implemented as a measure of immune competence and relationships between IA,
      inflammation, and antibody responses were explored using statistical modeling
      appropriate for integrating high-dimensional data sets. Our results show that
      markers of IA, such as coexpression of HLA antigen D related (HLA-DR) and CD38 on
      CD4+ T cells, exhibit strong associations with HIV infection but not with
      biological age. Certain variables that showed a strong relationship with aging,
      such as declining naive and CD38+ CD4 and CD8+ T cells, did so regardless of HIV
      infection. Interestingly, the variable of biological age was not identified in a
      predictive model as significantly impacting vaccine responses in either group,
      while distinct IA and inflammatory variables were closely associated with vaccine
      response in HIV-infected and -uninfected populations. These findings shed light
      on the most relevant and persistent immune defects during virological suppression
      with antiretroviral therapy.

PMID- 29046482
TI  - Blunted rise in brain glucose levels during hyperglycemia in adults with obesity
      and T2DM.
AB  - In rodent models, obesity and hyperglycemia alter cerebral glucose metabolism and
      glucose transport into the brain, resulting in disordered cerebral function as
      well as inappropriate responses to homeostatic and hedonic inputs. Whether
      similar findings are seen in the human brain remains unclear. In this study, 25
      participants (9 healthy participants; 10 obese nondiabetic participants; and 6
      poorly controlled, insulin- and metformin-treated type 2 diabetes mellitus (T2DM)
      participants) underwent 1H magnetic resonance spectroscopy scanning in the
      occipital lobe to measure the change in intracerebral glucose levels during a 2
      hour hyperglycemic clamp (glucose ~220 mg/dl). The change in intracerebral
      glucose was significantly different across groups after controlling for age and
      sex, despite similar plasma glucose levels at baseline and during hyperglycemia.
      Compared with lean participants, brain glucose increments were lower in
      participants with obesity and T2DM. Furthermore, the change in brain glucose
      correlated inversely with plasma free fatty acid (FFA) levels during
      hyperglycemia. These data suggest that obesity and poorly controlled T2DM
      progressively diminish brain glucose responses to hyperglycemia, which has
      important implications for understanding not only the altered feeding behavior,
      but also the adverse neurocognitive consequences associated with obesity and
      T2DM.

PMID- 29046483
TI  - Deficiency of Shank2 causes mania-like behavior that responds to mood
      stabilizers.
AB  - Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a
      variety of neuropsychiatric disorders, including autism spectrum disorders,
      schizophrenia, intellectual disability, and bipolar disorder, but the molecular
      mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly
      understood. We generated and characterized a line of Shank2 mutant mice by
      deleting exon 24 (Deltae24). Shank2Deltae24-/- mice engage in significantly
      increased locomotor activity, display abnormal reward-seeking behavior, are
      anhedonic, have perturbations in circadian rhythms, and show deficits in social
      and cognitive behaviors. While these phenotypes recapitulate the pleotropic
      behaviors associated with human SHANK2-related disorders, major behavioral
      features in these mice are reminiscent of bipolar disorder. For instance, their
      hyperactivity was augmented with amphetamine but was normalized with the mood
      stabilizers lithium and valproate. Shank2 deficiency limited to the forebrain
      recapitulated the bipolar mania phenotype. The composition and functions of NMDA
      and AMPA receptors were altered at Shank2-deficient synapses, hinting toward the
      mechanism underlying these behavioral abnormalities. Human genetic findings
      support construct validity, and the behavioral features in Shank2 Deltae24 mice
      support face and predictive validities of this model for bipolar mania. Further
      genetic studies to understand the contribution of SHANK2 deficiencies in bipolar
      disorder are warranted.

PMID- 29046484
TI  - T cells expressing chimeric antigen receptor promote immune tolerance.
AB  - Cellular therapies based on permanent genetic modification of conventional T
      cells have emerged as a promising strategy for cancer. However, it remains
      unknown if modification of T cell subsets, such as Tregs, could be useful in
      other settings, such as allograft transplantation. Here, we use a modular system
      based on a chimeric antigen receptor (CAR) that binds covalently modified mAbs to
      control Treg activation in vivo. Transient expression of this mAb-directed CAR
      (mAbCAR) in Tregs permitted Treg targeting to specific tissue sites and mitigated
      allograft responses, such as graft-versus-host disease. mAbCAR Tregs targeted to
      MHC class I proteins on allografts prolonged islet allograft survival and also
      prolonged the survival of secondary skin grafts specifically matched to the
      original islet allograft. Thus, transient genetic modification to produce mAbCAR
      T cells led to durable immune modulation, suggesting therapeutic targeting
      strategies for controlling alloreactivity in settings such as organ or tissue
      transplantation.

PMID- 29046485
TI  - Dimethyl fumarate increases fetal hemoglobin, provides heme detoxification, and
      corrects anemia in sickle cell disease.
AB  - Sickle cell disease (SCD) results from a point mutation in the beta-globin gene
      forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes,
      triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia.
      Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD.
      Nuclear factor (erythroid derived-2)-like 2 (Nrf2) is a transcription factor that
      triggers cytoprotective and antioxidant pathways to limit oxidative damage and
      inflammation and increases HbF synthesis in CD34+ stem cell-derived erythroid
      progenitors. We investigated the ability of dimethyl fumarate (DMF), a small
      molecule Nrf2 agonist, to activate gamma-globin transcription and enhance HbF in
      tissue culture and in murine and primate models. DMF recruited Nrf2 to the gamma
      globin promoters and the locus control region of the beta-globin locus in
      erythroleukemia cells, elevated HbF in SCD donor-derived erythroid progenitors,
      and reduced hypoxia-induced sickling. Chronic DMF administration in SCD mice
      induced HbF and increased Nrf2-dependent genes to detoxify heme and limit
      inflammation. This improved hematological parameters, reduced plasma-free Hb, and
      attenuated inflammatory markers. Chronic DMF administration to nonanemic primates
      increased gamma-globin mRNA in BM and HbF protein in rbc. DMF represents a
      potential therapy for SCD to induce HbF and augment vasoprotection and heme
      detoxification.

PMID- 29046486
TI  - Synaptopodin is upregulated by IL-13 in eosinophilic esophagitis and regulates
      esophageal epithelial cell motility and barrier integrity.
AB  - Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the
      esophagus mediated by an IL-13-driven epithelial cell transcriptional program.
      Herein, we show that the cytoskeletal protein synaptopodin (SYNPO), previously
      associated with podocytes, is constitutively expressed in esophageal epithelium
      and induced during allergic inflammation. In addition, we show that the SYNPO
      gene is transcriptionally and epigenetically regulated by IL-13 in esophageal
      epithelial cells. SYNPO was expressed in the basal layer of homeostatic
      esophageal epithelium, colocalized with actin filaments, and expanded into the
      suprabasal epithelium in EoE patients, where expression was elevated 25-fold
      compared with control individuals. The expression level of SYNPO in esophageal
      biopsies correlated with esophageal eosinophil density and was improved following
      anti-IL-13 treatment in EoE patients. In esophageal epithelial cells, SYNPO gene
      silencing reduced epithelial motility in a wound healing model, whereas SYNPO
      overexpression impaired epithelial barrier integrity and reduced esophageal
      differentiation. Taken together, we demonstrate that SYNPO is induced by IL-13 in
      vitro and in vivo, is a nonredundant regulator of epithelial cell barrier
      function and motility, and is likely involved in EoE pathogenesis.

PMID- 29046487
TI  - Autograft Valve-Sparing Root Replacement for Late Ross Failure during Quadruple
      Valve Surgery.
AB  - Approximately 25% of patients require reoperation within 15 yrs of a Ross
      procedure. Increasing experience with valve-sparing root replacement (VSRR) has
      led some surgeons to spare the autograft valve. Here, we demonstrate that all
      valves can be surgically repaired or replaced safely during autograft VSRR. As
      more patients are considered for this operation, coexistent mitral, tricuspid,
      and pulmonic valve dysfunction should not preclude salvage of the autograft
      valve, nor should autograft leaflet prolapse.

PMID- 29046488
TI  - Principles and Applications of Rabbit Models for Atherosclerosis Research.
AB  - Rabbits are one of the most used experimental animals for biomedical research,
      particularly as a bioreactor for the production of antibodies. However, many
      unique features of the rabbit have also made it as an excellent species for
      examining a number of aspects of human diseases such as atherosclerosis. Rabbits
      are phylogenetically closer to humans than rodents, in addition to their
      relatively proper size, tame disposition, and ease of use and maintenance in the
      laboratory facility. Due to their short life spans, short gestation periods, high
      numbers of progeny, low cost (compared with other large animals) and availability
      of genomics and proteomics, rabbits usually serve to bridge the gap between
      smaller rodents (mice and rats) and larger animals, such as dogs, pigs and
      monkeys, and play an important role in many translational research activities
      such as pre-clinical testing of drugs and diagnostic methods for patients. The
      principle of using rabbits rather than other animals as an experimental model is
      very simple: rabbits should be used for research, such as translational research,
      that is difficult to accomplish with other species. Recently, rabbit genome
      sequencing and transcriptomic profiling of atherosclerosis have been successfully
      completed, which has paved a new way for researchers to use this model in the
      future. In this review, we provide an overview of the recent progress using
      rabbits with specific reference to their usefulness for studying human
      atherosclerosis.

PMID- 29046489
TI  - Association between rotating night shift work and metabolic syndrome in Korean
      workers: differences between 8-hour and 12-hour rotating shift work.
AB  - This study aimed to analyze the association between the shift work schedule and
      metabolic syndrome (MetS). This is a retrospective longitudinal study based on
      the 2015 health checkup data of 2,090 workers evaluated for MetS in 2010 at a
      general hospital in Korea. The participants were divided according to their shift
      work schedule into daytime, three-shift (8-h rotation), and two-shift (12-h
      rotation) workers. The index that indicates the association between the shift
      work schedule and MetS is the odds ratio (OR) calculated using multivariate
      logistic regression. The analysis for the entire group of workers indicated that
      there was positive association between two-shift rotation and MetS (OR=1.58, 95%
      confidence interval [CI]: 1.09, 2.29). In the analysis of rotating night-shift
      workers, the years of rotating night shifts, frequency of night-shift work, and
      sleep disturbance were added to the confounding variables, and two-shift work
      remained positively associated with MetS (OR=1.72, 95% CI: 1.10, 2.70). The risk
      of MetS differs based on the shift work schedules they engage in. Hence,
      structural changes to the shift work schedules are required to prevent MetS in
      night-shift workers.

PMID- 29046490
TI  - Exposure to airborne endotoxin in Italian greenhouses: environmental analyses.
AB  - The peculiar characteristics of the greenhouses as confined spaces, microclimate
      and poor air exchange with the outside environment, encourage the development of
      a large number of biological agents. Endotoxin, is probably a major causative
      agent of occupational health problems. The objective of this study was to measure
      the concentrations of airborne endotoxin in greenhouses with different cultures.
      The influence of microclimate was studied in correlation with endotoxin levels
      and type of cultured vegetables. The data indicate that workers employed
      greenhouses are exposed to low levels of inhalable endotoxins; endotoxin
      concentrations do not correlate with the temperature and relative humidity
      values. A strong correlation between the leaf size and endotoxin concentration
      was observed. The mean concentration of endotoxins in the air of greenhouses is
      relatively low, however, there could be peaks of exposure during harvesting and
      eradication of broadleaf plants.

PMID- 29046491
TI  - Factors associated with adherence to recommendations to visit a physician after
      annual health checkups among Japanese employees: a cross-sectional observational
      study.
AB  - Periodic health checkups constitute an important public health strategy to
      prevent the onset of diseases and promote healthy behaviors. However, adherence
      to recommendations to undergo further medical examination after annual health
      checkups is not necessarily high. This study examined the factors related to
      adherence to recommendations among Japanese employees. We conducted a cross
      sectional study of 219 employees who had ignored recommendations to visit a
      physician for the previous 3 yr; we assessed their work- and life-related
      factors, health status, and health literacy. We analyzed the data of 103
      employees who met the inclusion criteria. Participants who lived alone and had a
      primary doctor, lower job demand, and lower self-rated health were significantly
      more likely to adhere to recommendations, suggesting that work- and life-related
      factors-rather than individual health literacy-may be more important. Further
      study is needed toward effective utilization of annual health checkups in the
      workplace.

PMID- 29046492
TI  - Newly breeding an inbred strain of ischemia-prone Mongolian gerbils and its
      reproduction and genetic characteristics.
AB  - The Mongolian gerbil has been a useful laboratory animal in many research fields,
      especially in ischemia studies. However, due to the variation of the circle of
      Willis (COW), the ischemic model is unstable and various. To solve this problem,
      we newly established an inbred strain of gerbils, restricting breeding and
      keeping to F23. The data on the breeding and growth of the animals are described
      in the present study. The genetic characteristics of F4 to F20 detected by
      microsatellite DNA and biochemical markers are also shown here. The results
      demonstrated that the frequency of ischemic model by unilateral carotid occlusion
      and the frequency of incomplete COW increased, increasing from 50% and 75% in F1
      to 88.89% and 100% in F20, respectively. The ratios of consistent patterns of COW
      in parents were positively related with the number of inbred generations. A
      reproductive performance analysis indicated that the average size of litters in
      the inbred gerbils was less than that of outbred gerbils and that adult body
      weight was also lower in inbred gerbils; also, the pups in the 2nd litter were
      the best ones chosen to reproduce. The genetic detection results indicated that
      26 out of 28 microsatellite loci and all 26 biochemical markers were homozygous
      in F20, showing comparably identical genetic composition in inbred gerbils. All
      the data demonstrated that an inbred strain of ischemia-prone gerbil has been
      established successfully. This strain can be used in stroke research and can
      largely reduce the number of animals needed in experiments.

PMID- 29046493
TI  - Current global standards for chemical protective clothing: how to choose the
      right protection for the right job?
AB  - The first standards for chemical protective clothing (CPC) emerged mid to late
      1980's and have evolved since as most standards are revisited every 5 yr. Over
      the past years, we have also seen a strengthening of the chemical and worker
      protection legislation around the globe (various forms of REACH) but also
      protection of workers. The most prevalent standards originate under the auspices
      of the International Standards Organisation (ISO), European Committee for
      Standardisation (CEN) or under various US standards organisations (e.g. NFPA,
      ASTM). Protective clothing against hazardous materials is required in many of the
      professional and non-professional activities of everyday life. Effective and
      adequate protection is important in many scenarios from household (e.g. cleaning
      agents, peroxides, acids and bases, paints), to agricultural (e.g. fuel,
      pesticides), to medical (e.g. pharmaceuticals and active ingredients), to
      industrial production (e.g. petro-chemicals, chemicals, paints, adhesive and
      coatings) but also manufacturing of many products (e.g. light bulbs, cars, semi
      conductors), during various emergency activities (e.g. boat, rail or road
      accidents as well as fire-fighting in an urban and industrial setting), and
      finally, military operations or response to incidents of terrorism. Nevertheless,
      CPC must remain the last line of defence whenever possible through a preference
      for less hazardous chemicals, less dangerous processes and handling operations,
      and by engineering controls to reduce and minimise human contact with the
      chemicals. This article provides information about the selection, use, care and
      maintenance (SUCAM) of protective clothing against chemical and microbiological
      hazards.

PMID- 29046494
TI  - A user-centred design process of new cold-protective clothing for offshore
      petroleum workers operating in the Barents Sea.
AB  - : Petroleum operations in the Barents Sea require personal protective clothing
      (PPC) to ensure the safety and performance of the workers. This paper describes
      the accomplishment of a user-centred design process of new PPC for offshore
      workers operating in this area. The user-centred design process was accomplished
      by mixed-methods. Insights into user needs and context of use were established by
      group interviews and on-the-job observations during a field-trip. The design was
      developed based on these insights, and refined by user feedback and participatory
      design. The new PPC was evaluated via field-tests and cold climate chamber tests.
      The insight into user needs and context of use provided useful input to the
      design process and contributed to tailored solutions. Providing users with
      clothing prototypes facilitated participatory design and iterations of design
      refinement. The group interviews following the final field test showed consensus
      of enhanced user satisfaction compared to PPC in current use. The final cold
      chamber test indicated that the new PPC provides sufficient thermal protection
      during the 60 min of simulated work in a wind-chill temperature of -25 degrees C.
      CONCLUSION: Accomplishing a user-centred design process contributed to new PPC
      with enhanced user satisfaction and included relevant functional solutions.

PMID- 29046495
TI  - Molecular epidemiological survey and genetic characterization of ovine
      gammaherpesvirus-2 in Mongolian livestock.
AB  - Sheep-associated malignant catarrhal fever (SA-MCF), caused by ovine
      gammaherpesvirus-2 (OvHV-2), is a fatal disease in all ruminants. The
      epidemiological survey and molecular characterization of OvHV-2 in Mongolian
      livestock were performed. Of 928 blood samples, 14 were positive for OvHV-2 in
      sheep and native cattle from Tsenkher County and in sheep from Lun County.
      Phylogenetic analyses revealed that the tegument gene of OvHV-2 sequences from
      Mongolian animals is identical to that in animals from Egypt, India, and Turkey,
      and is 98.0% similar to that in animals from Germany and Brazil. To our
      knowledge, this is the first confirmed report of OvHV-2 in Mongolian livestock,
      and could provide useful information for controlling SA-MCF.

PMID- 29046496
TI  - Fluoroscopic observation of the development of displaced abomasum in dairy cows.
AB  - To clarify the mechanisms underlying the development of displaced abomasum (DA),
      we repositioned DA in 12 cows by rolling and observed the course of
      redisplacement using X-ray fluoroscopy. Displacement of the abomasum was observed
      to follow three patterns: displacement to the left side of the abdominal cavity
      through the gap formed at the reticulum, atrium of the rumen and ventral sac of
      the rumen (n=7); displacement to the left side after cranial movement along the
      diaphragm (n=3); displacement to the right side after cranial movement along the
      diaphragm (n=2). These differences were considered to be associated with the
      rumen volume. To the best of our knowledge, this is the first study reporting the
      visual observation of the course of DA in dairy cows.

PMID- 29046498
TI  - Immunophenotypical analysis of pancreatic interstitial cells in the developing
      rat pancreas and myofibroblasts in the fibrotic pancreas in dogs and cats.
AB  - Pancreatic fibrosis develops as the results of the activity of myofibroblasts
      capable of producing collagens. The myofibroblasts derive from pancreatic
      interstitial cells, including pancreatic stellate cells (PSCs), which can express
      glial fibrillary acidic protein (GFAP). First, we investigated the expression
      patterns of vimentin, desmin, alpha-smooth muscle actin (alpha-SMA), Thy-1 and
      GFAP in the developing rat pancreas (in fetuses at 18 and 20 days, neonates from
      1 to 21 days, and adults). Interstitial cells in the developing pancreas
      expressed vimentin, desmin, GFAP and Thy-1 at varying degrees; interestingly, the
      reactivity for desmin and vimentin was the highest in fetuses. GFAP expression
      was consistent between fetuses and neonates, and Thy-1 reactivity transiently
      increased after birth; however, alpha-SMA-positive interstitial cells were rarely
      seen. Next, we analyzed the immunophenotypical characteristics of myofibroblasts
      appearing in pancreatic fibrosis in dogs and cats. With increasing fibrotic
      grade, myofibroblasts showed increased expression of vimentin, desmin and alpha
      SMA, in addition to increased GFAP expression. Collectively, pancreatic
      interstitial cells and myofibroblasts may have similar immunophenotypes, and
      myofibroblasts might originate partly from GFAP-expressing PSCs.

PMID- 29046497
TI  - Hypoxia increases glucose transporter 1 expression in bovine corpus luteum at the
      early luteal stage.
AB  - A major role of the corpus luteum (CL) is to produce progesterone (P4). The CL
      has immature vasculature shortly after ovulation, suggesting it exists under
      hypoxic conditions. Hypoxia-inducible factor-1 (HIF1) induces the expression of
      glucose transporter 1 (GLUT1). To clarify the physiological roles of GLUT1 in
      bovine CL, we examined GLUT1 mRNA expression in the CL under hypoxic conditions
      by quantitative RT-PCR. We also measured the effects of glucose (0-25 mM) and
      GLUT1 inhibitors (cytochalasin B, STF-31) on P4 production in bovine luteal
      cells. GLUT1 mRNA expression in bovine CL was higher at the early luteal stage
      compared to the other later stages. Hypoxia (3% O2) increased GLUT1 mRNA
      expression in early luteal cells, but not in mid luteal cells. Glucose (0-25 mM)
      increased P4 production in early luteal cells, but not in mid luteal cells. Both
      GLUT1 inhibitors decreased P4 production in early and mid luteal cells. Overall,
      the results suggest that GLUT1 (possibly induced by hypoxic conditions in the
      early CL) plays a role in the establishment and development of bovine CL,
      especially in supporting luteal P4 synthesis at the early luteal stage.

PMID- 29046500
TI  - Comparative genomics of Tetragenococcus halophilus.

PMID- 29046499
TI  - The assessment of total antioxidant capacity and superoxide dismutase levels, and
      the possible role of manganese superoxide dismutase polymorphism in acromegaly.
AB  - Oxidative status is attributed to endothelial dysfunction and might be one of the
      key mechanisms of endothelial dysfunction in acromegaly. In this study, we aimed
      to investigate the effect of acromegaly on superoxide dismutase (SOD) and total
      antioxidant capacity (TAC) levels, and the possible influence of human manganese
      superoxide dismutase (MnSOD) polymorphism on these levels. 51 acromegaly patients
      and 57 age and sex matched healthy subjects were recruited to the study in
      Bezmialem Vakif University Hospital between 2011 and 2014. The median SOD and TAC
      levels were 42.7 (33-60) pg/mL and 1,313.7 (155-1,902) MUM in acromegaly; and
      46.3 (38-95) pg/mL and 1,607.3 (195-1,981) MUM in healthy subjects (p < 0.001, p
      < 0.001). SOD levels were decreased in controlled and uncontrolled patients
      compared to healthy subjects (p = 0.05 and p = 0.002, respectively). Controlled
      and uncontrolled acromegaly displayed significantly decreased levels of TAC
      compared to healthy subjects (p < 0.05 and p < 0.001, respectively). SOD levels
      were not associated with MnSOD polymorphisms in acromegaly. In conclusion, this
      study showed that acromegaly was associated with decreased levels of SOD and TAC,
      and controlling the disease activity could not adequately improve these levels.

PMID- 29046501
TI  - Characterization of amylolytic enzyme overproducing mutant of Aspergillus
      luchuensis obtained by ion beam mutagenesis.
AB  - Aspergillus luchuensis is a kuro (black) koji fungus that has been used as a
      starch degrader for the awamori- and shochu-making industries in Japan. In this
      study, we investigated the effect of ion beam irradiation on A. luchuensis
      RIB2601 and obtained a high starch-degrading mutant strain U1. Strain U1 showed
      reduced growth rate, whereas it showed higher alpha-amylase, glucoamylase, and
      alpha-glucosidase activities on a mycelial mass basis than the wild type (wt)
      strain both on agar plates and in rice koji. In addition, strain U1 showed higher
      N-acetylglucosamine content in the cell wall and higher sensitivity to calcofluor
      white, suggesting a deficiency in cell wall composition. Interestingly, produced
      protein showed higher expression of acid-labile alpha-amylase (AmyA) and
      glucoamylase (GlaA) in strain U1, although real-time RT-PCR indicated no
      significant change in the transcription of the amyA or glaA gene. These results
      suggested that the high amylolytic activity of strain U1 is attributable to a
      high AmyA and GlaA production level, but the elevated production is not due to
      transcriptional regulation of the corresponding genes. Furthermore, RNA-seq
      analysis indicated that strain U1 shows transcriptional changes in at least 604
      genes related to oxidation-reduction, transport, and glucosamine-containing
      compound metabolic processes, which may be involved in the deficient cell wall
      composition of strain U1.

PMID- 29046502
TI  - Correlation between Thyroid Stimulating Hormone and Renal Function in Euthyroid
      Residents of Japan: Results from the Kyushu and Okinawa Population Study (KOPS).
AB  - AIM: The present large-scale Japanese population study was performed to evaluate
      the relation between the serum thyroid stimulating hormone (TSH) level and renal
      function. METHODS: Out of 1,374 residents who participated in a free public
      physical examination between 2010 and 2011, we evaluated the data of 888
      participants for whom the serum TSH level and estimated glomerular filtration
      rate (eGFR) were successfully measured. The participants were categorized into
      three groups based on TSH levels (normal TSH, <=2.4; high-normal TSH, 2.5-4.4;
      and subclinical hypothyroid, >=4.5 MUIU/mL). Multiple linear regression analysis
      adjusted for cardiovascular risk factors was performed to determine the
      relationship between serum TSH level and renal function. RESULTS: The mean+/-SD
      TSH level was 2.0+/-1.4 MUIU/mL, and 75.9% (n=674) of the participants had
      normal, 17.9% (n=159) had high-normal, and 6.2% (n=55) had subclinical
      hypothyroid TSH levels. The mean eGFR significantly decreased with increased TSH
      levels (normal TSH, 79.3+/-14.1; high-normal TSH, 77.4+/-13.0; and subclinical
      hypothyroid, 72.3+/-12.2 mL/min/1.73 m2: P for trend <0.01). Multiple linear
      regression analysis extracted log-transformed TSH level as an independent factor
      correlated with eGFR in the high-normal TSH group (beta=-0.18, P=0.02).
      CONCLUSIONS: Our findings demonstrated a significant correlation between serum
      TSH levels and eGFR in high-normal TSH participants. In healthy individuals, high
      normal TSH levels indicate increased the risk of chronic kidney disease.

PMID- 29046503
TI  - Effects of a Novel Selective Peroxisome Proliferator-Activated Receptor alpha
      Modulator K-877 (Pemafibrate) on Postprandial hyperlipidemia.

PMID- 29046504
TI  - Radiographic Assessment on Magnetic Resonance Imaging after Percutaneous
      Endoscopic Lumbar Foraminotomy.
AB  - Percutaneous endoscopic lumbar foraminotomy (ELF) is a novel minimally invasive
      technique used to treat lumbar foraminal stenosis. However, the validity of
      foraminal decompression based on quantitative assessment using magnetic resonance
      imaging (MRI) has not yet been established. The objective of this study was to
      investigate the radiographic efficiency of ELF using MRI. Radiographic changes of
      neuroforamen were measured based on pre- and postoperative MRI findings. Images
      were blindly analyzed by two observers for foraminal stenosis grade and foraminal
      dimensions. The intraclass correlation coefficient (ICC) and k statistic were
      calculated to determine interobserver agreement. Thirty-five patients with 40
      neuroforamen were evaluated. The mean visual analog scale (VAS) score improved
      from 8.4 to 2.1, and the mean Oswestry disability index (ODI) improved from 65.9
      to 19.2. Overall, 91.4% of the patients achieved good or excellent outcomes. The
      mean grade of foraminal stenosis significantly improved from 2.63 to 0.68. There
      were significant increases in the mean foraminal area (FA) from 50.05 to 92.03
      mm2, in mean foraminal height (FH) from 11.36 to 13.47 mm, in mean superior
      foraminal width (SFW) from 6.43 to 9.27 mm, and in mean middle foraminal width
      (MFW) from 1.47 to 78 mm (P < 0.001). Interobserver agreements for preoperative
      and postoperative measurements were good to excellent with the exception of SFW.
      In conclusion, foraminal dimensions and grades of foraminal stenosis
      significantly improved after ELF. These findings may enhance the clinical
      relevance of endoscopic lumbar foraminal decompression.

PMID- 29046505
TI  - Bipolar Endo-Epicardial Radiofrequency Ablation of Arrhythmia Originating From
      the Left Ventricular Summit.

PMID- 29046506
TI  - Analysis of differentially expressed proteins in Muscovy duck embryo fibroblasts
      infected with virulent and attenuated Muscovy duck reovirus by two-dimensional
      polyacrylamide gel electrophoresis.
AB  - Muscovy duck reovirus (MDRV) belongs to the Orthoreovirus genus of the Reoviridae
      family, which is a significant poultry pathogen leading to high morbidity and
      mortality in ducklings. However, the pathogenesis of the virus is not well
      understood. In the present study, two-dimensional (2D) polyacrylamide gel
      electrophoresis (PAGE) combined with LC-MS-MS was used to identify differentially
      expressed proteins between Muscovy duck embryo fibroblasts (MDEF) infected with
      virulent (MV9710 strain) and attenuated (CA strain) MDRV and non-infected MDEFs.
      A total of 115 abundant protein spots were identified. Of these, 59 of
      differentially expressed proteins were detected, with functions in metabolism and
      utilization of carbohydrates and nucleotides, anti-stress, and regulation of
      immune and cellular process. GO analysis of the identified proteins showed that
      they belonged to the classes molecular function (141 proteins), cellular
      component (62 proteins), and biological process (146 proteins). The results were
      validated by qRT-PCR, which suggests that the analysis method of 2D PAGE combined
      with LC-MS-MS used in this study is reliable. This study lays a foundation for
      further investigation of the biology of MDRV infection in MDEF.

PMID- 29046507
TI  - Subretinal implantation of Okayama University-type retinal prosthesis (OURePTM)
      in canine eyes by vitrectomy.
AB  - Okayama University-type retinal prosthesis (OURePTM) is a photoelectric dye
      coupled polyethylene film which generates electric potential in response to light
      and stimulates nearby neurons. This study aims to test surgical feasibility of
      subretinal implantation and functional durability of dye-coupled films in the
      subretinal space. The dye-coupled films were implanted subretinally by 25-gauge
      vitrectomy in the right eye of 11 normal beagle dogs: 2 dogs served for film
      removal after 5-month film implantation, 3 dogs for film removal after 3-month
      film implantation, 3 dogs for 3-month film implantation and pathological
      examination, and 3 dogs for sham surgery. The surface electric potential of the
      removed dye-coupled films in response to light was measured by the Kelvin Probe
      system. At surgery, rolled-up dye-coupled films in 5 * 5 mm square size could be
      inserted into subretinal space of retinal detachment induced by fluid injection
      with a 38-gauge polyimide tip. Retinal attachment was maintained by silicone oil
      injection in vitreous cavity. At autopsy, the retina in all dogs maintained the
      ganglion cell layer, inner and outer nuclear layers while it lost the outer
      segments in some part. All 5 sheets of removed dye-coupled films maintained the
      dye color. One sheet of the 5-month implanted film showed proportional increase
      of surface potential in response to increasing light intensity. Subretinal
      implantation of OURePTM by vitrectomy was technically feasible in canine eyes,
      and OURePTM maintained the function of generating light-evoked surface potential
      after 5 months in subretinal implantation.

PMID- 29046508
TI  - The MARCKS protein amount is differently regulated by calpain during toxic
      effects of methylmercury between SH-SY5Y and EA.hy926 cells.
AB  - Methylmercury (MeHg) is an environmental pollutant that shows severe toxicity to
      humans and animals. However, the molecular mechanisms mediating MeHg toxicity are
      not completely understood. We have previously reported that the MARCKS protein is
      involved in the MeHg toxicity to SH-SY5Y neuroblastoma and EA.hy926 vascular
      endothelial cell lines. In addition, calpain, a Ca2+-dependent protease, is
      suggested to be associated with the MeHg toxicity. Because MARCKS is known as a
      substrate of calpain, we studied the relation between calpain activation and
      cleavage of MARCKS and its role in MeHg toxicity. In SH-SY5Y cells, MeHg
      decreased cell viability along with increased calcium mobilization, calpain
      activation and a decrease in MARCKS amounts. However, pretreatment with calpain
      inhibitors attenuated the decrease in cell viability and MARCKS amount induced
      only by 1 uM but not by 3 uM MeHg. In cells with a MARCKS knockdown, calpain
      inhibitors failed to attenuate the decrease in cell viability caused by MeHg. In
      EA.hy926 cells, although MeHg caused calcium mobilization and a decrease in
      MARCKS levels, calpain activation was not observed. These results indicate that
      the participation of calpain in the regulation of MARCKS amounts is dependent on
      the cell type and concentration of MeHg. In SH-SY5Y cells, calpain-mediated
      proteolysis of MARCKS is involved in cytotoxicity induced by a low concentration
      of MeHg.

PMID- 29046509
TI  - Full shift assessment of back and head postures in overhead crane operators with
      and without symptoms.
AB  - OBJECTIVES: Prolonged sitting with a flexed back and neck is recognized as being
      associated with an increased risk of neck and back pain disorders among overhead
      crane operators. The aim of this study was to compare back and head postures over
      a full shift of work between operators who experience back and neck pain, and
      healthy operators. METHODS: In a first phase, the prevalence of musculoskeletal
      symptoms was assessed using the Nordic questionnaire among 120 crane operators.
      Based on first phase results, 17 operators with back/neck disorders were matched
      with 15 healthy operators based on age and selected to participate in the second
      phase of the study. Postures and movements were continuously measured over an 8 h
      shift using inclinometers. RESULTS: The highest 12-month prevalence of
      musculoskeletal disorders was found in the lower back, neck and knees. Case and
      control groups differed significantly in back and head flexion angles at the 50th
      percentiles APDF (p < 0.05). There was also a significant difference in the time
      spent working in an extreme posture of the back and head between groups (p <
      0.05). CONCLUSIONS: This is the first study to document work postures assumed
      during a full work shift and to compare postures between symptomatic and healthy
      overhead crane operators. Physical exposure in case group operators was
      characterized by more awkward and extreme postures in the back and head. The
      results of this study demonstrate that effective prevention strategies directed
      towards musculoskeletal disorders are required that address awkward work postures
      for overhead crane operators.

PMID- 29046511
TI  - Human resource factors associated with workplace safety and health education of
      small manufacturing businesses in Korea.
AB  - OBJECTIVES: Human resources (HR) are essential indicators of safety and health
      (SH) status, and HR can be key sources of workplace safety management such as
      safety and health education at work (SHEW). This study analyzed significant HR
      factors associated with SHEW of small manufacturing businesses in Korea. METHODS:
      The secondary data of the 2012 Korea Occupational Safety and Health Trend Survey
      were used to achieve this research purpose. A total of 2,089 supervisors or
      managers employed in the small manufacturing businesses completed the interview
      survey. Survey businesses were selected by multiple stratified sampling method
      based on industry code, business size, and region in Korea. The survey included
      workplace characteristics of HR and SHEW. RESULTS: SHEW was significantly related
      to business size, occupational injury incidence in the previous year, foreign and
      elderly worker employment, presence of site supervisors, and presence of SH
      committees (p <.05). SHEW for office workers, non-office workers, and newcomers
      was associated with business size, presence of site supervisors, and presence of
      SH committees in logistic regression analysis (p <.001). Businesses with 30-49
      workers conducted SHEW 3.64 times more than did businesses with 5 to fewer than
      10 workers. The companies that had occupational injuries in the previous year
      conducted SHEW 1.68 times more than the others. The businesses that had site
      supervisors and committees conducted SHEW 2.30 and 2.18 times more, respectively,
      than others. CONCLUSIONS: Site supervisors and SH committees were significant HR
      factors that improved SHEW in small manufacturing businesses.

PMID- 29046512
TI  - Guidelines for personal exposure monitoring of chemicals: Part II.
AB  - This Document, "Guidelines for personal exposure monitoring of chemicals" ("this
      Guideline"), has been prepared by "The Committee for Personal Exposure
      Monitoring" ("the Committee") of the Expert Division of Occupational Hygiene &
      Ergonomics, Japan Society for Occupational Health. Considering the background of
      the growing importance of personal exposure monitoring in risk assessment and the
      need to prepare for the introduction of monitoring using personal samplers from
      an administrative perspective in recent years, the Committee was organized in
      November 2012. The Committee has prepared this Guideline as a "practical
      guideline" for personal exposure monitoring, so as to offer proposals and
      recommendations to the members of the Japan Society for Occupational Health and
      to society in general. The scope of this Guideline covers all chemical substances
      and all related workplaces regarded as targets for general assessment and the
      management of risk. It thus is not to be considered to comment on legal
      regulations and methodology. The main text provides the basic methods and
      concepts of personal exposure monitoring, while 31 "Appendices" are provided in
      this Guideline throughout the series; technical descriptions, statistical bases,
      and actual workplace examples are provided in these appendices, to assist better
      understanding. The personal exposure monitoring described as per this Guideline
      is equivalent to an "expert-centered basic method to reasonably proceed with the
      assessment and management of risk at workplaces." It is considered that
      practicing and expanding on this method will significantly contribute in
      reforming the overall framework of occupational hygiene management in Japan.

PMID- 29046510
TI  - Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard
      assessment.
AB  - OBJECTIVES: This report reviews the carcinogenicity of multi-walled carbon
      nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight
      fibrous MWCNT. METHODS: MWCNTs were administered to mice and rats by
      intraperitoneal injection, intrascrotal injection, subcutaneous injection,
      intratracheal instillation and inhalation. RESULTS: Intraperitoneal injection of
      MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection
      induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N
      (another straight fibrous MWCNT) induced both lung carcinoma and pleural
      mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7
      promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of
      MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with
      increasing concentration of airborne MWNT-7 and increasing duration of exposure.
      CONCLUSIONS: Straight, fibrous MWCNTs exerted carcinogenicity in experimental
      animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a
      principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect
      level-based approach, we calculated that the occupational exposure limit (OEL) of
      MWNT-7 for cancer protection is 0.15 MUg/m3 for a human worker. Further studies
      on the effects of the shape and size of MWCNT fibers and mode of action on the
      carcinogenicity are required.

PMID- 29046513
TI  - History and Practice of Thyroid Fine-Needle Aspiration in China, Based on
      Retrospective Study of the Practice in Shandong University Qilu Hospital.
AB  - Cytology in China developed from nothing and underwent a long journey from
      gynecologic cytology to that of all organs, laying a solid foundation for new
      developments in the 21st century. Thyroid fine-needle aspiration (FNA) was
      primarily developed in an endocrinology department and then in the clinical
      laboratory department or pathology department in the 1970-80s. Wrights staining
      is popular in endocrine and clinical laboratory departments, while hematoxylin
      and eosin staining is common in pathology. Liquid based cytology is not common in
      thyroid FNA cytology, while BRAF V600E mutation analysis has been the most
      popular molecular test. The history and practice of thyroid FNA practice in China
      were reviewed based on retrospective study of the practice in Qilu Hospital of
      Shandong University.

PMID- 29046514
TI  - Protein Phosphatase Magnesium-Dependent 1delta (PPM1D) Expression as a Prognostic
      Marker in Adult Supratentorial Diffuse Astrocytic and Oligodendroglial Tumors.
AB  - BACKGROUND: Protein phosphatase magnesium-dependent 1delta (PPM1D) is a p53
      induced serine/threonine phosphatase, which is overexpressed in various human
      cancers. A recent study reported that a mutation in the PPM1D gene is associated
      with poor prognosis in brainstem gliomas. In this study, we evaluated the utility
      of PPM1D as a prognostic biomarker of adult supratentorial diffuse astrocytic and
      oligodendroglial tumors. METHODS: To investigate PPM1D protein expression, mRNA
      expression, and copy number changes, immunohistochemistry, RNAscope in situ
      hybridization, and fluorescence in situ hybridization were performed in 84 adult
      supratentorial diffuse gliomas. We further analyzed clinical characteristics and
      overall survival (OS) according to PPM1D protein expression, and examined its
      correlation with other glioma biomarkers such as isocitrate dehydrogenase (IDH)
      mutation, and p53 expression. RESULTS: Forty-six cases (54.8%) were PPM1D
      positive. PPM1D expression levels were significantly correlated with PPM1D
      transcript levels (p= .035), but marginally with PPM1D gene amplification
      (p=.079). Patients with high-grade gliomas showed a higher frequency of PPM1D
      expression than those with low-grade gliomas (p <.001). Multivariate analysis
      demonstrated that PPM1D expression (hazard ratio [HR], 2.58; p=.032), age over 60
      years (HR, 2.55; p=.018), and IDH1 mutation (HR, 0.18; p=.002) were significantly
      independent prognostic factors; p53 expression had no prognostic significance
      (p=.986). The patients with tumor expressing PPM1D showed a shorter OS (p=.003).
      Moreover, patients with tumor harboring wild-type IDH1 and PPM1D expression had
      the worst OS (p<.001). CONCLUSIONS: Our data suggest that a subset of gliomas
      express PPM1D; PPM1D expression is a significant marker of poor prognosis in
      adult supratentorial diffuse astrocytic and oligodendroglial tumors.

PMID- 29046515
TI  - Thyroid Fine-Needle Aspiration in Taiwan: The History and Current Practice.
AB  - In Taiwan, thyroid cancer is the most common endocrine gland malignancy and the
      incidence of thyroid cancer has increased four-fold in the past two decades. Fine
      needle aspiration is an accurate and cost-effective method of evaluating thyroid
      nodules and has been the gold-standard diagnostic tool for thyroid tumors in
      Taiwan since the 1980s. This article reviews the history, current practice,
      reporting systems, training, and quality assurance for thyroid fine-needle
      aspiration cytology in Taiwan.

PMID- 29046516
TI  - Current Practices of Thyroid Fine-Needle Aspiration in Asia: A Missing Voice.

PMID- 29046517
TI  - A Rare Association of Congenital Asplenia with Jejunal Arteriovenous
      Malformation.
AB  - BACKGROUND Isolated congenital asplenia is a poorly understood and rare form of
      primary immunodeficiency, often associated with life-threatening infections. CASE
      REPORT We encountered a unique case of a 22-year-old asplenic male who presented
      with severe iron-deficiency anemia secondary to occult gastrointestinal bleeding
      since age 15. Our extensive work-up confirmed jejunal arteriovenous malformations
      as the source of the bleed. Six months after the treatment, the patient has
      reported no further episodes of gastrointestinal bleeding and his hemoglobin has
      remained stable. CONCLUSIONS A comprehensive literature review confirmed that
      this is the first reported case of adult congenital asplenia associated with
      arteriovenous malformation in the United States. The relationship of isolated
      congenital asplenia and arteriovenous malformation-associated bleeding remains
      unknown at this time; we postulate that this may be a congenital syndrome on its
      own. Obscure bleeding in the presence of rare anomalies such as asplenia should
      be investigated as one of the important causes of unexplained intestinal
      arteriovenous malformations.

PMID- 29046518
TI  - Pretreatment with Oxycodone Simultaneously Reduces Etomidate-Induced Myoclonus
      and Rocuronium-Induced Withdrawal Movements During Rapid-Sequence Induction.
AB  - BACKGROUND Etomidate and rocuronium are often paired in rapid-sequence anesthesia
      induction. However, the effect of pretreatment with oxycodone on myoclonic and
      withdrawal movements has not been previously investigated. The aim of this study
      was to evaluate the effects of oxycodone on the incidence and severity of
      etomidate-induced myoclonus and rocuronium-induced nociceptive withdrawal
      movements during rapid-sequence anesthesia induction. MATERIAL AND METHODS We
      randomly divided 120 patients into the saline group (group S) and the oxycodone
      group (group O) (n=60 in each group). Patients received 0.05 mg/kg oxycodone or
      saline intravenously 2 min before administration of 0.3 mg/kg etomidate. The
      occurrence and severity of myoclonus were assessed after administration of
      etomidate, then rocuronium was injected, followed by evaluation of withdrawal
      movements. RESULTS The total frequency of involuntary movements following
      sequential administration of etomidate and rocuronium was significantly lower in
      Group O than in Group S (28.3% vs. 90%, p<0.001). The total frequency and grade 3
      severity of myoclonus following etomidate injection in Group O was significantly
      lower than in Group S (25.0% vs. 63.3% for total frequency; 0 vs. 10 for grade 3
      severity, P<0.001). The total frequency and grade 3 intensity of withdrawal
      movements were significantly less in Group O than in Group S (6.7% vs. 73.3% for
      total frequency; 0 vs. 11 for grade 3 intensity, P<0.001). CONCLUSIONS Oxycodone
      is effective for simultaneously preventing etomidate-induced myoclonus and
      rocuronium-induced withdrawal movements during general anesthesia induction.

PMID- 29046520
TI  - The impact of salt intake during and after pregnancy.
AB  - Although high blood pressure before pregnancy is associated with a risk of
      gestational hypertension and preeclampsia, no convincing evidence has been
      produced to show that dietary salt reduction helps in the prevention and
      treatment of hypertension during pregnancy. Thus the current guidelines do not
      recommend a sodium restriction during pregnancy to prevent gestational
      hypertension and the development of preeclampsia. However, the long-term impact
      of hypertensive disorders of pregnancy for life-threatening diseases later in
      life is a critical issue. Gestational hypertension could contribute to the risk
      of developing hypertension later in life, and recent studies have suggested that
      gestational hypertension and preeclampsia are linked to cardiovascular
      complications. In this article, we provide an overview of the current
      perspectives on the salt intake of pregnant women and consider both the short
      term influence and the impact beyond the perinatal period.

PMID- 29046519
TI  - The effects of anti-hypertensive drugs and the mechanism of hypertension in
      vascular smooth muscle cell-specific ATP2B1 knockout mice.
AB  - ATP2B1 is a gene associated with hypertension. We reported previously that mice
      lacking ATP2B1 in vascular smooth muscle cells (VSMC ATP2B1 KO mice) exhibited
      high blood pressure and increased intracellular calcium concentration. The
      present study was designed to investigate whether lack of the ATP2B1 gene causes
      a higher response to calcium channel blockers (CCBs) than to other types of anti
      hypertensive drugs. Both VSMC ATP2B1 KO and control mice were administered anti
      hypertensive drugs while monitoring blood pressure shifts. We also examined the
      association of nitric oxide synthase (NOS) activity in those mice to investigate
      whether another mechanism of hypertension existed. VSMC ATP2B1 KO mice exhibited
      significantly greater anti-hypertensive effects with a single injection of
      nicardipine, but the effects of an angiotensin II receptor blocker (ARB), an
      alpha-blocker and amlodipine on blood pressure were all similar to control mice.
      However, long-term treatment with amlodipine, but not an ARB, significantly
      decreased the blood pressure of KO mice compared with control mice. Both mRNA and
      protein expression levels of the L-type calcium channel were significantly
      upregulated in KO VSMCs. There were no alterations in neural NOS protein
      expression of VSMCs or in urinary NO production between the two groups. VSMC
      ATP2B1 KO mice had a higher response to CCBs for blood pressure-lowering effects
      than other anti-hypertensive drugs. These results mean that increased
      intracellular calcium concentration in VSMCs due to lack of ATP2B1 and subsequent
      activation of L-type calcium channels mainly affects blood pressure and suggests
      increased susceptibility to CCBs in this type of hypertension.

PMID- 29046523
TI  - European infrastructures for sustainable agriculture.

PMID- 29046525
TI  - Streptococci target inflammasome.

PMID- 29046524
TI  - Maintaining the common grounds.

PMID- 29046526
TI  - Hitting malaria where it hurts.

PMID- 29046527
TI  - Better support translational research.

PMID- 29046528
TI  - Plasmid vesicles mimicking virions.

PMID- 29046529
TI  - Cheese, phages and anti-CRISPRs.

PMID- 29046530
TI  - New options to treat influenza B.

PMID- 29046531
TI  - Diversity in stomatal function is integral to modelling plant carbon and water
      fluxes.
AB  - Stomatal pores on leaf surfaces respond to environmental and physiological
      signals to regulate leaf gas exchange. Mathematical models can predict stomatal
      conductance (g s), with one parameter (m or g l) reflecting the sensitivity of g
      s to the photosynthetic rate (A), atmospheric carbon dioxide concentration and
      atmospheric humidity, and a second parameter (g 0) representing the minimum g s.
      Such models are solved iteratively with a photosynthesis model to form the core
      of many models of crop or ecosystem carbon and water fluxes. For three decades, g
      s models have frequently been used assuming fixed parameter values for m or g 1
      and g 0 across species and major plant functional types. This study of temperate
      tree species reveals significant interspecific variation in stomatal function.
      Applying species-specific parameterizations substantially reduced error in model
      predictions of g s by 34 to 64% and A by 52 to 60% and resulted in significant
      correlation between modelled and measured values. This work challenges the long
      held assumption of fixed parameter values and, in doing so, suggests an approach
      for reducing modelling error across a wide range of ecological and agricultural
      applications.

PMID- 29046532
TI  - Cradles and museums of Antarctic teleost biodiversity.
AB  - Isolated in one of the most extreme marine environments on Earth, teleost fish
      diversity in Antarctica's Southern Ocean is dominated by one lineage: the
      notothenioids. Throughout the past century, the long-term persistence of this
      unique marine fauna has become increasingly threatened by regional atmospheric
      and, to a lesser extent oceanic, warming. Developing an understanding of how
      historical temperature shifts have shaped source-sink dynamics for Antarctica's
      teleost lineages provides critical insight for predicting future demographic
      responses to climate change. We use a combination of phylogenetic and
      biogeographic modelling to show that high-latitude Antarctic nearshore habitats
      have been an evolutionary sink for notothenioid species diversity. Contrary to
      expectations from island biogeographic theory, lower latitude regions of the
      Southern Ocean that include the northern Antarctic Peninsula and peripheral
      island archipelagos act as source areas to continental diversity. These
      peripheral areas facilitate both the generation of new species and repeated
      colonization of nearshore Antarctic continental regions. Our results provide
      historical context to contemporary trends of global climate change that threaten
      to invert these evolutionary dynamics.

PMID- 29046533
TI  - Anatomical integration of the sacral-hindlimb unit coordinated by GDF11 underlies
      variation in hindlimb positioning in tetrapods.
AB  - Elucidating how body parts from different primordia are integrated during
      development is essential for understanding the nature of morphological evolution.
      In tetrapod evolution, while the position of the hindlimb has diversified along
      with the vertebral formula, the mechanism responsible for this coordination has
      not been well understood. However, this synchronization suggests the presence of
      an evolutionarily conserved developmental mechanism that coordinates the
      positioning of the hindlimb skeleton derived from the lateral plate mesoderm with
      that of the sacral vertebrae derived from the somites. Here we show that GDF11
      secreted from the posterior axial mesoderm is a key factor in the integration of
      sacral vertebrae and hindlimb positioning by inducing Hox gene expression in two
      different primordia. Manipulating the onset of GDF11 activity altered the
      position of the hindlimb in chicken embryos, indicating that the onset of Gdf11
      expression is responsible for the coordinated positioning of the sacral vertebrae
      and hindlimbs. Through comparative analysis with other vertebrate embryos, we
      also show that each tetrapod species has a unique onset timing of Gdf11
      expression, which is tightly correlated with the anteroposterior levels of the
      hindlimb bud. We conclude that the evolutionary diversity of hindlimb positioning
      resulted from heterochronic shifts in Gdf11 expression, which led to coordinated
      shifts in the sacral-hindlimb unit along the anteroposterior axis.

PMID- 29046534
TI  - Evidence complacency hampers conservation.

PMID- 29046535
TI  - Decision-making psychology can bolster conservation.

PMID- 29046536
TI  - Honeybee spillover reshuffles pollinator diets and affects plant reproductive
      success.
AB  - During the past decades, managed honeybee stocks have increased globally. Managed
      honeybees are particularly used within mass-flowering crops and often spill over
      to adjacent natural habitats after crop blooming. Here, we uniquely show the
      simultaneous impact that honeybee spillover has on wild plant and animal
      communities in flower-rich woodlands via changes in plant-pollinator network
      structure that translate into a direct negative effect on the reproductive
      success of a dominant wild plant. Honeybee spillover leads to a re-assembly of
      plant-pollinator interactions through increased competition with other pollinator
      species. Moreover, honeybee preference for the most abundant plant species
      reduces its seed set, driven by high honeybee visitation rates that prevent
      pollen tube growth. Our study therefore calls for an adequate understanding of
      the trade-offs between providing pollination services to crops and the effects
      that managed pollinators might have on wild plants and pollinators.

PMID- 29046537
TI  - Robust assessment comes of age.

PMID- 29046538
TI  - Publisher correction: The spatial scales of species coexistence.
AB  - An error during production led to a truncation of the final two sentences in the
      abstract, which should have read 'In so doing, this framework substantially
      reframes current approaches to spatial community ecology. Quantifying the spatial
      scales of species coexistence will permit the next important advance in our
      understanding of the maintenance of diversity in nature, and should improve the
      contribution of community ecology to biodiversity conservation.' These have been
      corrected in all versions of the Perspective.

PMID- 29046539
TI  - Publisher correction: Oil exposure disrupts early life-history stages of coral
      reef fishes via behavioural impairments.
AB  - In the version of this Article originally published, a statistic relating to the
      northern Great Barrier Reef was attributed to the Great Barrier Reef as a whole.
      The sentence should have read 'In 2016 alone, more than 35% of corals on the
      northern Great Barrier Reef are estimated to have died following the worst
      bleaching event ever recorded'. This has been corrected in all versions of the
      Article.

PMID- 29046540
TI  - Compensatory mutations improve general permissiveness to antibiotic resistance
      plasmids.
AB  - Horizontal gene transfer mediated by broad-host-range plasmids is an important
      mechanism of antibiotic resistance spread. While not all bacteria maintain
      plasmids equally well, plasmid persistence can improve over time, yet no general
      evolutionary mechanisms have emerged. Our goal was to identify these mechanisms
      and to assess if adaptation to one plasmid affects the permissiveness to others.
      We experimentally evolved Pseudomonas sp. H2 containing multidrug resistance
      plasmid RP4, determined plasmid persistence and cost using a joint experimental
      modelling approach, resequenced evolved clones, and reconstructed key mutations.
      Plasmid persistence improved in fewer than 600 generations because the fitness
      cost turned into a benefit. Improved retention of naive plasmids indicated that
      the host evolved towards increased plasmid permissiveness. Key chromosomal
      mutations affected two accessory helicases and the RNA polymerase beta-subunit.
      Our and other findings suggest that poor plasmid persistence can be caused by a
      high cost involving helicase-plasmid interactions that can be rapidly
      ameliorated.

PMID- 29046542
TI  - Decadal ecosystem response to an anomalous melt season in a polar desert in
      Antarctica.
AB  - Amplified climate change in polar regions is significantly altering regional
      ecosystems, yet there are few long-term records documenting these responses. The
      McMurdo Dry Valleys (MDV) cold desert ecosystem is the largest ice-free area of
      Antarctica, comprising soils, glaciers, meltwater streams and permanently ice
      covered lakes. Multi-decadal records indicate that the MDV exhibited a distinct
      ecosystem response to an uncharacteristic austral summer and ensuing climatic
      shift. A decadal summer cooling phase ended in 2002 with intense glacial melt
      ('flood year')-a step-change in water availability triggering distinct changes in
      the ecosystem. Before 2002, the ecosystem exhibited synchronous behaviour:
      declining stream flow, decreasing lake levels, thickening lake ice cover,
      decreasing primary production in lakes and streams, and diminishing soil
      secondary production. Since 2002, summer air temperatures and solar flux have
      been relatively consistent, leading to lake level rise, lake ice thinning and
      elevated stream flow. Biological responses varied; one stream cyanobacterial mat
      type immediately increased production, but another stream mat type, soil
      invertebrates and lake primary productivity responded asynchronously a few years
      after 2002. This ecosystem response to a climatic anomaly demonstrates
      differential biological community responses to substantial perturbations, and the
      mediation of biological responses to climate change by changes in physical
      ecosystem properties.

PMID- 29046543
TI  - Ecosystem shift after a hot event.

PMID- 29046544
TI  - Palaeoclimate explains a unique proportion of the global variation in soil
      bacterial communities.
AB  - The legacy impacts of past climates on the current distribution of soil microbial
      communities are largely unknown. Here, we use data from more than 1,000 sites
      from five separate global and regional datasets to identify the importance of
      palaeoclimatic conditions (Last Glacial Maximum and mid-Holocene) in shaping the
      current structure of soil bacterial communities in natural and agricultural
      soils. We show that palaeoclimate explains more of the variation in the richness
      and composition of bacterial communities than current climate. Moreover,
      palaeoclimate accounts for a unique fraction of this variation that cannot be
      predicted from geographical location, current climate, soil properties or plant
      diversity. Climatic legacies (temperature and precipitation anomalies from the
      present to ~20 kyr ago) probably shape soil bacterial communities both directly
      and indirectly through shifts in soil properties and plant communities. The
      ability to predict the distribution of soil bacteria from either palaeoclimate or
      current climate declines greatly in agricultural soils, highlighting the fact
      that anthropogenic activities have a strong influence on soil bacterial
      diversity. We illustrate how climatic legacies can help to explain the current
      distribution of soil bacteria in natural ecosystems and advocate that climatic
      legacies should be considered when predicting microbial responses to climate
      change.

PMID- 29046541
TI  - A multi-species synthesis of physiological mechanisms in drought-induced tree
      mortality.
AB  - Widespread tree mortality associated with drought has been observed on all
      forested continents and global change is expected to exacerbate vegetation
      vulnerability. Forest mortality has implications for future biosphere-atmosphere
      interactions of carbon, water and energy balance, and is poorly represented in
      dynamic vegetation models. Reducing uncertainty requires improved mortality
      projections founded on robust physiological processes. However, the proposed
      mechanisms of drought-induced mortality, including hydraulic failure and carbon
      starvation, are unresolved. A growing number of empirical studies have
      investigated these mechanisms, but data have not been consistently analysed
      across species and biomes using a standardized physiological framework. Here, we
      show that xylem hydraulic failure was ubiquitous across multiple tree taxa at
      drought-induced mortality. All species assessed had 60% or higher loss of xylem
      hydraulic conductivity, consistent with proposed theoretical and modelled
      survival thresholds. We found diverse responses in non-structural carbohydrate
      reserves at mortality, indicating that evidence supporting carbon starvation was
      not universal. Reduced non-structural carbohydrates were more common for
      gymnosperms than angiosperms, associated with xylem hydraulic vulnerability, and
      may have a role in reducing hydraulic function. Our finding that hydraulic
      failure at drought-induced mortality was persistent across species indicates that
      substantial improvement in vegetation modelling can be achieved using thresholds
      in hydraulic function.

PMID- 29046545
TI  - Academic conferences urgently need environmental policies.

PMID- 29046546
TI  - Hard times for the Brazilian environment.

PMID- 29046547
TI  - Mapping the global potential for marine aquaculture.
AB  - Marine aquaculture presents an opportunity for increasing seafood production in
      the face of growing demand for marine protein and limited scope for expanding
      wild fishery harvests. However, the global capacity for increased aquaculture
      production from the ocean and the relative productivity potential across
      countries are unknown. Here, we map the biological production potential for
      marine aquaculture across the globe using an innovative approach that draws from
      physiology, allometry and growth theory. Even after applying substantial
      constraints based on existing ocean uses and limitations, we find vast areas in
      nearly every coastal country that are suitable for aquaculture. The development
      potential far exceeds the space required to meet foreseeable seafood demand;
      indeed, the current total landings of all wild-capture fisheries could be
      produced using less than 0.015% of the global ocean area. This analysis
      demonstrates that suitable space is unlikely to limit marine aquaculture
      development and highlights the role that other factors, such as economics and
      governance, play in shaping growth trajectories. We suggest that the vast amount
      of space suitable for marine aquaculture presents an opportunity for countries to
      develop aquaculture in a way that aligns with their economic, environmental and
      social objectives.

PMID- 29046548
TI  - Long-term relationships.

PMID- 29046549
TI  - Adult frogs and tadpoles have different macroevolutionary patterns across the
      Australian continent.
AB  - Developmental changes through an animal's life are generally understood to
      contribute to the resulting adult morphology. Possible exceptions are species
      with complex life cycles, where individuals pass through distinct ecological and
      morphological life stages during their ontogeny, ending with metamorphosis to the
      adult form. Antagonistic selection is expected to drive low genetic correlations
      between life stages, theoretically permitting stages to evolve independently.
      Here we describe, using Australian frog radiation, the evolutionary consequences
      on morphological evolution when life stages are under different selective
      pressures. We use morphometrics to characterize body shape of tadpoles and adults
      across 166 species of frog and investigate similarities in the two resulting
      morphological spaces (morphospaces) to test for concerted evolution across
      metamorphosis in trait variation during speciation. A clear pattern emerges:
      Australian frogs and their tadpoles are evolving independently; their markedly
      different morphospaces and contrasting estimated evolutionary histories of body
      shape diversification indicate that different processes are driving morphological
      diversification at each stage. Tadpole morphospace is characterized by rampant
      homoplasy, convergent evolution and high lineage density. By contrast, the adult
      morphospace shows greater phylogenetic signal, low lineage density and divergent
      evolution between the main clades. Our results provide insight into the
      macroevolutionary consequences of a biphasic life cycle.

PMID- 29046550
TI  - Gene flow favours local adaptation under habitat choice in ciliate microcosms.
AB  - Local adaptation is assumed to occur under limited gene flow. However, habitat
      matching theory predicts dispersal should favour rather than hinder local
      adaptation when individuals selectively disperse towards habitats maximizing
      their performance. We provide experimental evidence that local adaptation to the
      upper margin of a species' thermal niche is favoured by dispersal with habitat
      choice, but hindered under random dispersal. Our study challenges the idea that
      high gene flow precludes local adaptation, and provides unique experimental
      evidence of habitat choice as an overlooked mechanism responsible for adaptation
      under rapid environmental changes.

PMID- 29046551
TI  - Population extinctions can increase metapopulation persistence.
AB  - Metapopulations persist when local populations are rapidly recolonized following
      local extinctions. Such persistence requires asynchrony; simultaneous crashes of
      all populations would leave no source of recolonization. We show theoretically
      and experimentally that catastrophic population extinctions themselves can
      promote metapopulation persistence, by preventing spatial synchrony and thus
      enhancing recolonization. We refer to this behaviour as the 'spatial hydra
      effect': as with the mythical hydra that grows two new heads when one is removed,
      extinctions can increase recolonization. The effect is robust, occurring in a
      wide range of theoretical models exhibiting cyclic or quasi-cyclic population
      dynamics. In a laboratory microcosm experiment using cyclic protist predator-prey
      metapopulations, catastrophic perturbations wiping out populations but leaving
      the patch otherwise unchanged increased metapopulation persistence when high
      dispersal rates would otherwise have led to spatially synchronous extinctions of
      all populations. We discuss several candidate examples of the spatial hydra
      effect in nature.

PMID- 29046552
TI  - A green epoch in the evolutionary history of biological energy sources.

PMID- 29046553
TI  - Pesticide reduces bumblebee colony initiation and increases probability of
      population extinction.
AB  - Pollinators are in global decline and agricultural pesticides are a potential
      driver of this. Recent studies have suggested that pesticides may significantly
      impact bumblebee colonies-an important and declining group of pollinators. Here,
      we show that colony-founding queens, a critical yet vulnerable stage of the
      bumblebee lifecycle, are less likely to initiate a colony after exposure to
      thiamethoxam, a neonicotinoid insecticide. Bombus terrestris queens were exposed
      to field-relevant levels of thiamethoxam and two natural stressors: the parasite
      Crithidia bombi and varying hibernation durations. Exposure to thiamethoxam
      caused a 26% reduction in the proportion of queens that laid eggs, and advanced
      the timing of colony initiation, although we did not detect impacts of any
      experimental treatment on the ability of queens to produce adult offspring during
      the 14-week experimental period. As expected from previous studies, the
      hibernation duration also had an impact on egg laying, but there was no
      significant interaction with insecticide treatment. Modelling the impacts of a
      26% reduction in colony founding on population dynamics dramatically increased
      the likelihood of population extinction. This shows that neonicotinoids can
      affect this critical stage in the bumblebee lifecycle and may have significant
      impacts on population dynamics.

PMID- 29046554
TI  - The veiled ecological danger of rising sea levels.

PMID- 29046555
TI  - Mother's curse neutralizes natural selection against a human genetic disease over
      three centuries.
AB  - According to evolutionary theory, mitochondria could be poisoned gifts that
      mothers transmit to their sons. This is because mutations harmful to males are
      expected to accumulate in the mitochondrial genome, the so-called 'mother's
      curse'. However, the contribution of the mother's curse to the mutation load in
      nature remains largely unknown and hard to predict, because compensatory
      mechanisms could impede the spread of deleterious mitochondria. Here we provide
      evidence for the mother's curse in action over 290 years in a human population.
      We studied a mutation causing Leber's hereditary optical neuropathy, a disease
      with male-biased prevalence and which has long been suspected to be maintained in
      populations by the mother's curse. Male carriers showed a low fitness relative to
      non-carriers and to females, mostly explained by their high rate of infant
      mortality. Despite poor male fitness, selection analysis predicted a slight
      (albeit non-significant) increase in frequency, which sharply contrasts with the
      35.5% per-generation decrease predicted if mitochondrial DNA transmission had
      been through males instead of females. Our results are therefore even suggestive
      of positive selection through the female line that may exacerbate effects of the
      mother's curse. This study supports a contribution of the mother's curse to the
      reduction of male lifespan, uncovering a large fitness effect associated with a
      single mitochondrial variant.

PMID- 29046556
TI  - The former Iron Curtain still drives biodiversity-profit trade-offs in German
      agriculture.
AB  - Agricultural intensification drives biodiversity loss and shapes farmers' profit,
      but the role of legacy effects and detailed quantification of ecological-economic
      trade-offs are largely unknown. In Europe during the 1950s, the Eastern communist
      bloc switched to large-scale farming by forced collectivization of small farms,
      while the West kept small-scale private farming. Here we show that large-scale
      agriculture in East Germany reduced biodiversity, which has been maintained in
      West Germany due to >70% longer field edges than those in the East. In contrast,
      profit per farmland area in the East was 50% higher than that in the West,
      despite similar yield levels. In both regions, switching from conventional to
      organic farming increased biodiversity and halved yield levels, but doubled
      farmers' profits. In conclusion, European Union policy should acknowledge the
      surprisingly high biodiversity benefits of small-scale agriculture, which are on
      a par with conversion to organic agriculture.

PMID- 29046557
TI  - A multidimensional framework for studying social predation strategies.
AB  - Social predation-the act of hunting and feeding with others-is one of the most
      successful life-history traits in the animal kingdom. Although many predators
      hunt and feed together, a diversity of mechanisms exist by which individuals
      forage socially. However, a comprehensive framework capturing this diversity is
      lacking, preventing us from better understanding cooperative forms of predation,
      and how such behaviours have evolved and been maintained over time. We outline a
      framework of social predation that describes five key behavioural dimensions:
      sociality, communication, specialization, resource sharing, and dependence. By
      reviewing examples of social predation, we demonstrate the strength of a
      multidimensional approach, highlighting key commonalities and differences among
      species, and informative cross-dimensional correlations. These patterns highlight
      different potential evolutionary pathways and end-points across a
      multidimensional social predation spectrum.

PMID- 29046558
TI  - Ocean space for seafood.

PMID- 29046559
TI  - Linked sustainability challenges and trade-offs among fisheries, aquaculture and
      agriculture.
AB  - Fisheries and aquaculture make a crucial contribution to global food security,
      nutrition and livelihoods. However, the UN Sustainable Development Goals separate
      marine and terrestrial food production sectors and ecosystems. To sustainably
      meet increasing global demands for fish, the interlinkages among goals within and
      across fisheries, aquaculture and agriculture sectors must be recognized and
      addressed along with their changing nature. Here, we assess and highlight
      development challenges for fisheries-dependent countries based on analyses of
      interactions and trade-offs between goals focusing on food, biodiversity and
      climate change. We demonstrate that some countries are likely to face double
      jeopardies in both fisheries and agriculture sectors under climate change. The
      strategies to mitigate these risks will be context-dependent, and will need to
      directly address the trade-offs among Sustainable Development Goals, such as
      halting biodiversity loss and reducing poverty. Countries with low adaptive
      capacity but increasing demand for food require greater support and capacity
      building to transition towards reconciling trade-offs. Necessary actions are
      context-dependent and include effective governance, improved management and
      conservation, maximizing societal and environmental benefits from trade,
      increased equitability of distribution and innovation in food production,
      including continued development of low input and low impact aquaculture.

PMID- 29046561
TI  - The curse of the Filles du Roy.

PMID- 29046560
TI  - Ecosystem functioning is enveloped by hydrometeorological variability.
AB  - Terrestrial ecosystem processes, and the associated vegetation carbon dynamics,
      respond differently to hydrometeorological variability across timescales, and so
      does our scientific understanding of the underlying mechanisms. Long-term
      variability of the terrestrial carbon cycle is not yet well constrained and the
      resulting climate-biosphere feedbacks are highly uncertain. Here we present a
      comprehensive overview of hydrometeorological and ecosystem variability from
      hourly to decadal timescales integrating multiple in situ and remote-sensing
      datasets characterizing extra-tropical forest sites. We find that ecosystem
      variability at all sites is confined within a hydrometeorological envelope across
      sites and timescales. Furthermore, ecosystem variability demonstrates long-term
      persistence, highlighting ecological memory and slow ecosystem recovery rates
      after disturbances. However, simulation results with state-of-the-art process
      based models do not reflect this long-term persistent behaviour in ecosystem
      functioning. Accordingly, we develop a cross-time-scale stochastic framework that
      captures hydrometeorological and ecosystem variability. Our analysis offers a
      perspective for terrestrial ecosystem modelling and paves the way for new model
      data integration opportunities in Earth system sciences.

PMID- 29046563
TI  - Publisher Correction: The global distribution of tetrapods reveals a need for
      targeted reptile conservation.
AB  - In this Article originally published, owing to a technical error, the author
      'Laurent Chirio' was mistakenly designated as a corresponding author in the HTML
      version, the PDF was correct. This error has now been corrected in the HTML
      version. Further, in Supplementary Table 3, the authors misspelt the surname of
      'Danny Meirte'; this file has now been replaced.

PMID- 29046564
TI  - Risky times and risky places interact to affect prey behaviour.
AB  - Both short-term and long-term variation in predation risk can affect the
      behaviour of prey, thus affecting growth, reproduction, survival and population
      dynamics. Inferences about the strength of such 'risk effects' in the wild have
      been limited by a lack of studies that relate antipredator responses to the
      magnitude of direct predation, measure responses of prey to risk from complete
      predator guilds, and quantify risk in more than one way. Here, we quantify
      behavioural responses of a complete ungulate prey guild to long-term and short
      term variation in risks from all of the large predators in Liuwa Plain National
      Park, with known patterns of direct predation. Our analysis allows the first
      direct test for interaction between responses to long-term and short-term risk in
      the wild, and reveals that prey vigilance responds strongly to locations with
      high long-term risk when short-term risk is high, but not when short-term risk is
      low. This result has broad ramifications for the design and interpretation of
      field studies of antipredator behaviour, its costs and its consequences for
      population dynamics.

PMID- 29046562
TI  - Ecological and evolutionary approaches to managing honeybee disease.
AB  - Honeybee declines are a serious threat to global agricultural security and
      productivity. Although multiple factors contribute to these declines, parasites
      are a key driver. Disease problems in honeybees have intensified in recent years,
      despite increasing attention to addressing them. Here we argue that we must focus
      on the principles of disease ecology and evolution to understand disease
      dynamics, assess the severity of disease threats, and control these threats via
      honeybee management. We cover the ecological context of honeybee disease,
      including both host and parasite factors driving current transmission dynamics,
      and then discuss evolutionary dynamics including how beekeeping management
      practices may drive selection for more virulent parasites. We then outline how
      ecological and evolutionary principles can guide disease mitigation in honeybees,
      including several practical management suggestions for addressing short- and long
      term disease dynamics and consequences.

PMID- 29046565
TI  - Agricultural intensification without biodiversity loss is possible in grassland
      landscapes.
AB  - Grassland biodiversity in managed landscapes is threatened by land-use
      intensification, but is also dependent on low-intensity management. Solutions
      that allow for both agricultural production and species conservation may be
      realized either on individual grasslands, by adjusting management intensity, or
      at the landscape level, when grasslands are managed at different intensities.
      Here we use a dataset of more than 1,000 arthropod species collected in more than
      100 grasslands along gradients of productivity, to assess the reaction of
      individual species to changes in productivity. We defined a range of land-use
      strategies and evaluated their effects on overall production and on species
      abundances. We show that conservation of arthropods can be improved without
      reducing overall production. We also find that production can be increased
      without jeopardizing conservation. Conservation and production could, however,
      not be maximized simultaneously at the landscape level, emphasizing that
      management goals need to be clearly defined.

PMID- 29046566
TI  - The Pliocene marine megafauna extinction and its impact on functional diversity.
AB  - The end of the Pliocene marked the beginning of a period of great climatic
      variability and sea-level oscillations. Here, based on a new analysis of the
      fossil record, we identify a previously unrecognized extinction event among
      marine megafauna (mammals, seabirds, turtles and sharks) during this time, with
      extinction rates three times higher than in the rest of the Cenozoic, and with
      36% of Pliocene genera failing to survive into the Pleistocene. To gauge the
      potential consequences of this event for ecosystem functioning, we evaluate its
      impacts on functional diversity, focusing on the 86% of the megafauna genera that
      are associated with coastal habitats. Seven (14%) coastal functional entities
      (unique trait combinations) disappeared, along with 17% of functional richness
      (volume of the functional space). The origination of new genera during the
      Pleistocene created new functional entities and contributed to a functional shift
      of 21%, but minimally compensated for the functional space lost. Reconstructions
      show that from the late Pliocene onwards, the global area of the neritic zone
      significantly diminished and exhibited amplified fluctuations. We hypothesize
      that the abrupt loss of productive coastal habitats, potentially acting alongside
      oceanographic alterations, was a key extinction driver. The importance of area
      loss is supported by model analyses showing that animals with high energy
      requirements (homeotherms) were more susceptible to extinction. The extinction
      event we uncover here demonstrates that marine megafauna were more vulnerable to
      global environmental changes in the recent geological past than previously
      thought.

PMID- 29046567
TI  - Molecular signatures of fossil leaves provide unexpected new evidence for extinct
      plant relationships.
AB  - Gene sequences form the primary basis for understanding the relationships among
      extant plant groups, but genetic data are unavailable from fossils to evaluate
      the affinities of extinct taxa. Here we show that geothermally resistant fossil
      cuticles of seed-bearing plants, analysed with Fourier transform infrared (FTIR)
      spectroscopy and hierarchical cluster analysis (HCA), retain biomolecular suites
      that consistently distinguish major taxa even after experiencing different
      diagenetic histories. Our results reveal that similarities between the cuticular
      biochemical signatures of major plant groups (extant and fossil) are mostly
      consistent with recent phylogenetic hypotheses based on molecular and
      morphological data. Our novel chemotaxonomic data also support the hypothesis
      that the extinct Nilssoniales and Bennettitales are closely allied, but only
      distantly related to Cycadales. The chemical signature of the cuticle of
      Czekanowskia (Leptostrobales) is strongly similar to that of Ginkgo leaves and
      supports a close evolutionary relationship between these groups. Finally, our
      results also reveal that the extinct putative araucariacean, Allocladus, when
      analysed through HCA, is grouped closer to Ginkgoales than to conifers. Thus, in
      the absence of modern relatives yielding molecular information, FTIR spectroscopy
      provides valuable proxy biochemical data complementing morphological characters
      to distinguish fossil taxa and to help elucidate extinct plant relationships.

PMID- 29046568
TI  - Negative density dependence mediates biodiversity-productivity relationships
      across scales.
AB  - Regional species diversity generally increases with primary productivity whereas
      local diversity-productivity relationships are highly variable. This scale
      dependence of the biodiversity-productivity relationship highlights the
      importance of understanding the mechanisms that govern variation in species
      composition among local communities, which is known as beta-diversity. Hypotheses
      to explain changes in beta-diversity with productivity invoke multiple mechanisms
      operating at local and regional scales, but the relative importance of these
      mechanisms is unknown. Here we show that changes in the strength of local density
      dependent interactions within and among tree species explain changes in beta
      diversity across a subcontinental-productivity gradient. Stronger conspecific
      relative to heterospecific negative density dependence in more productive regions
      was associated with higher local diversity, weaker habitat partitioning (less
      species sorting), and homogenization of community composition among sites (lower
      beta-diversity). Regional processes associated with changes in species pools had
      limited effects on beta-diversity. Our study suggests that systematic shifts in
      the strength of local interactions within and among species might generally
      contribute to some of the most prominent but poorly understood gradients in
      global biodiversity.

PMID- 29046569
TI  - The ecology of rural poverty.

PMID- 29046570
TI  - General ecological models for human subsistence, health and poverty.
AB  - The world's rural poor rely heavily on their immediate natural environment for
      subsistence and suffer high rates of morbidity and mortality from infectious
      diseases. We present a general framework for modelling subsistence and health of
      the rural poor by coupling simple dynamic models of population ecology with those
      for economic growth. The models show that feedbacks between the biological and
      economic systems can lead to a state of persistent poverty. Analyses of a wide
      range of specific systems under alternative assumptions show the existence of
      three possible regimes corresponding to a globally stable development
      equilibrium, a globally stable poverty equilibrium and bistability. Bistability
      consistently emerges as a property of generalized disease-economic systems for
      about a fifth of the feasible parameter space. The overall proportion of
      parameters leading to poverty is larger than that resulting in healthy/wealthy
      development. All the systems are found to be most sensitive to human disease
      parameters. The framework highlights feedbacks, processes and parameters that are
      important to measure in studies of rural poverty to identify effective pathways
      towards sustainable development.

PMID- 29046571
TI  - Induced defences in plants reduce herbivory by increasing cannibalism.
AB  - Plants are attacked by myriad herbivores, and many plants exhibit anti-herbivore
      defences. We tested the hypothesis that induced defences benefit tomato plants by
      encouraging insects to eat other members of their species. We found that defences
      that promote cannibalism benefit tomatoes in two ways: cannibalism directly
      reduces herbivore abundance, and cannibals eat significantly less plant material.
      This previously unknown means of defence may alter plant-herbivore dynamics,
      plant evolution and pathogen transmission.

PMID- 29046572
TI  - Nutrient-dependent growth underpinned the Ediacaran transition to large body
      size.
AB  - Macroscale rangeomorph fossils, with characteristic branching fronds, appear (571
      Myr ago) after the Gaskiers glaciation (580 Myr ago). However, biological
      mechanisms of size growth and potential connections to ocean geochemistry were
      untested. Using micro-computerized tomography and photographic measurements,
      alongside mathematical and computer models, we demonstrate that growth of
      rangeomorph branch internodes declined as their relative surface area decreased.
      This suggests that frond size and shape were directly responsive to nutrient
      uptake.

PMID- 29046573
TI  - Sex-specific evolution during the diversification of live-bearing fishes.
AB  - Natural selection is often assumed to drive parallel functional diversification
      of the sexes. But males and females exhibit fundamental differences in their
      biology, and it remains largely unknown how sex differences affect
      macroevolutionary patterns. On microevolutionary scales, we understand how
      natural and sexual selection interact to give rise to sex-specific evolution
      during phenotypic diversification and speciation. Here we show that ignoring sex
      specific patterns of functional trait evolution misrepresents the
      macroevolutionary adaptive landscape and evolutionary rates for 112 species of
      live-bearing fishes (Poeciliidae). Males and females of the same species evolve
      in different adaptive landscapes. Major axes of female morphology were correlated
      with environmental variables but not reproductive investment, while male
      morphological variation was primarily associated with sexual selection. Despite
      the importance of both natural and sexual selection in shaping sex-specific
      phenotypic diversification, species diversification was overwhelmingly associated
      with ecological divergence. Hence, the inter-predictability of mechanisms of
      phenotypic and species diversification may be limited in many systems. These
      results underscore the importance of explicitly addressing sex-specific
      diversification in empirical and theoretical frameworks of evolutionary
      radiations to elucidate the roles of different sources of selection and
      constraint.

PMID- 29046574
TI  - Amotz Zahavi (1928-2017).

PMID- 29046575
TI  - Oil exposure disrupts early life-history stages of coral reef fishes via
      behavioural impairments.
AB  - Global demand for energy and oil-based products is progressively introducing
      petrogenic polycyclic aromatic hydrocarbons (PAHs) into sensitive marine
      environments, primarily from fossil-fuel exploration, transport, and urban and
      industrial runoff. These toxic pollutants are found worldwide, yet the long-term
      ecological effects on coral reef ecosystems are unknown. Here, we demonstrate
      that oil exposure spanning PAH concentrations that are environmentally relevant
      for many coastal marine ecosystems (<=5.7 MUg l-1), including parts of the Great
      Barrier Reef, Red Sea, Asia and the Caribbean, causes elevated mortality and
      stunted growth rates in six species of pre-settlement coral reef fishes, spanning
      two evolutionarily distinct families (Pomacentridae and Lethrinidae).
      Furthermore, oil exposure alters habitat settlement and antipredator behaviours,
      causing reduced sheltering, shoaling and increased risk taking, all of which
      exacerbate predator-induced mortality during recruitment. These results suggest a
      previously unknown path, whereby oil and PAH exposure impair higher-order
      cognitive processing and behaviours necessary for the successful settlement and
      survival of larval fishes. This emphasizes the risks associated with industrial
      activities within at-risk ecosystems.

PMID- 29046576
TI  - A sex-chromosome inversion causes strong overdominance for sperm traits that
      affect siring success.
AB  - Male reproductive success depends on the competitive ability of sperm to
      fertilize the ova, which should lead to strong selection on sperm
      characteristics. This raises the question of how heritable variation in sperm
      traits is maintained. Here we show that in zebra finches (Taeniopygia guttata)
      nearly half of the variance in sperm morphology is explained by an inversion on
      the Z chromosome with a 40% allele frequency in the wild. The sperm of males that
      are heterozygous for the inversion had the longest midpieces and the highest
      velocity. Furthermore, such males achieved the highest fertility and the highest
      siring success, both within-pair and extra-pair. Males homozygous for the derived
      allele show detrimental sperm characteristics and the lowest siring success. Our
      results suggest heterozygote advantage as the mechanism that maintains the
      inversion polymorphism and hence variance in sperm design and in fitness.

PMID- 29046577
TI  - Biodiversity at risk under future cropland expansion and intensification.
AB  - Agriculture is the leading driver of biodiversity loss. However, its future
      impact on biodiversity remains unclear, especially because agricultural
      intensification is often neglected, and high path-dependency is assumed when
      forecasting agricultural development-although the past suggests that shock events
      leading to considerable agricultural change occur frequently. Here, we
      investigate the possible impacts on biodiversity of pathways of expansion and
      intensification. Our pathways are not built to reach equivalent production
      targets, and therefore they should not be directly compared; they instead
      highlight areas at risk of high biodiversity loss across the entire option space
      of possible agricultural change.   Based on an extensive database of biodiversity
      responses to agriculture, we find 30% of species richness and 31% of species
      abundances potentially lost because of agricultural expansion across the Amazon
      and Afrotropics. Only 21% of high-risk expansion areas in the Afrotropics overlap
      with protected areas (compared with 43% of the Neotropics). Areas at risk of
      biodiversity loss from intensification are found in India, Eastern Europe and the
      Afromontane region (7% species richness, 13% abundance loss). Many high-risk
      regions are not adequately covered by conservation prioritization schemes, and
      have low national conservation spending and high agricultural growth. Considering
      rising agricultural demand, we highlight areas where timely land-use planning may
      proactively mitigate biodiversity loss.

PMID- 29046578
TI  - A sex-linked supergene controls sperm morphology and swimming speed in a
      songbird.
AB  - Sperm competition is an important selective force in many organisms. As a result,
      sperm have evolved to be among the most diverse cells in the animal kingdom.
      However, the relationship between sperm morphology, sperm motility and
      fertilization success is only partially understood. The extent to which between
      male variation is heritable is largely unknown, and remarkably few studies have
      investigated the genetic architecture of sperm traits, especially sperm
      morphology. Here we use high-density genotyping and gene expression profiling to
      explore the considerable sperm trait variation that exists in the zebra finch
      Taeniopygia guttata. We show that nearly all of the genetic variation in sperm
      morphology is caused by an inversion polymorphism on the Z chromosome acting as a
      'supergene'. These results provide a striking example of two evolutionary genetic
      predictions. First, that in species where females are the heterogametic sex,
      genetic variation affecting sexually dimorphic traits will accumulate on the Z
      chromosome. Second, recombination suppression at the inversion allows beneficial
      dominant alleles to become fixed on whichever haplotype they first arise, without
      being exchanged onto other haplotypes. Finally, we show that the inversion
      polymorphism will be stably maintained by heterozygote advantage, because
      heterozygous males have the fastest and most successful sperm.

PMID- 29046579
TI  - A general scaling law reveals why the largest animals are not the fastest.
AB  - Speed is the fundamental constraint on animal movement, yet there is no general
      consensus on the determinants of maximum speed itself. Here, we provide a general
      scaling model of maximum speed with body mass, which holds across locomotion
      modes, ecosystem types and taxonomic groups. In contrast to traditional power-law
      scaling, we predict a hump-shaped relationship resulting from a finite
      acceleration time for animals, which explains why the largest animals are not the
      fastest. This model is strongly supported by extensive empirical data (474
      species, with body masses ranging from 30 MUg to 100 tonnes) from terrestrial as
      well as aquatic ecosystems. Our approach unravels a fundamental constraint on the
      upper limit of animal movement, thus enabling a better understanding of realized
      movement patterns in nature and their multifold ecological consequences.

PMID- 29046580
TI  - Supergene yields super sperm.

PMID- 29046581
TI  - Sticking to the speed limits.

PMID- 29046583
TI  - Parallel genome reduction in symbionts descended from closely related free-living
      bacteria.
AB  - Endosymbiosis plays an important role in ecology and evolution, but fundamental
      aspects of the origin of intracellular symbionts remain unclear. The extreme age
      of many symbiotic relationships, lack of data on free-living ancestors and
      uniqueness of each event hinder investigations. Here, we describe multiple
      strains of the bacterium Polynucleobacter that evolved independently and under
      similar conditions from closely related, free-living ancestors to become obligate
      endosymbionts of closely related ciliate hosts. As these genomes reduced in
      parallel from similar starting states, they provide unique glimpses into the
      mechanisms underlying genome reduction in symbionts. We found that gene loss is
      contingently lineage-specific, with no evidence for ordered streamlining.
      However, some genes in otherwise disrupted pathways are retained, possibly
      reflecting cryptic genetic network complexity. We also measured substitution
      rates between many endosymbiotic and free-living pairs for hundreds of genes,
      which showed that genetic drift, and not mutation pressure, is the main non
      selective factor driving molecular evolution in endosymbionts.

PMID- 29046582
TI  - Maximizing ecological and evolutionary insight in bisulfite sequencing data sets.
AB  - Genome-scale bisulfite sequencing approaches have opened the door to ecological
      and evolutionary studies of DNA methylation in many organisms. These approaches
      can be powerful. However, they introduce new methodological and statistical
      considerations, some of which are particularly relevant to non-model systems.
      Here, we highlight how these considerations influence a study's power to link
      methylation variation with a predictor variable of interest. Relative to current
      practice, we argue that sample sizes will need to increase to provide robust
      insights. We also provide recommendations for overcoming common challenges and an
      R Shiny app to aid in study design.

PMID- 29046584
TI  - The spatial scales of species coexistence.
AB  - Understanding how species diversity is maintained is a foundational problem in
      ecology and an essential requirement for the discipline to be effective as an
      applied science. Ecologists' understanding of this problem has rapidly matured,
      but this has exposed profound uncertainty about the spatial scales required to
      maintain species diversity. Here we define and develop this frontier by proposing
      the coexistence-area relationship-a real relationship in nature that can be used
      to understand the determinants of the scale-dependence of diversity maintenance.
      The coexistence-area relationship motivates new empirical techniques for
      addressing important, unresolved problems about the influence of demographic
      stochasticity, environmental heterogeneity and dispersal on scale-dependent
      patterns of diversity. In so doing, this framework substantially reframes current
      approaches to spatial community ecology. Quantifying the spatial scales of
      species coexistence will permit the next important advance in our understanding
      of the maintenance of diversity in nature, and should improve the contribution of
      community ecology to biodiversity conservation.

PMID- 29046585
TI  - Infectious disease management must be evolutionary.

PMID- 29046586
TI  - Cancer (r)evolution.

PMID- 29046587
TI  - The unpredictable road to reduction.

PMID- 29046588
TI  - Preserve Precambrian fossil heritage from mining.

PMID- 29046589
TI  - The shadow of diclofenac hangs over European vultures.

PMID- 29046590
TI  - Evolution can beat disease.

PMID- 29046591
TI  - Effect of maternal predator exposure on the ability of stickleback offspring to
      generalize a learned colour-reward association.
AB  - Maternal stress can have long-term negative consequences for offspring learning
      performance. However, it is unknown whether these maternal effects extend to the
      ability of offspring to apply previously learned information to new situations.
      In this study, we first demonstrate that juvenile threespine sticklebacks,
      Gasterosteus aculeatus, are indeed capable of generalizing an association between
      a colour and a food reward learned in one foraging context to a new foraging
      context (i.e. they can apply previously learned knowledge to a new situation).
      Next, we examined whether this ability to generalize was affected by maternal
      predator stress. We manipulated whether mothers were repeatedly chased by a model
      predator while yolking eggs (i.e. before spawning) and then assessed the learning
      performance of their juvenile offspring in groups and pairs using a colour
      discrimination task that associated a colour with a food reward. We found that
      maternal predator exposure affected the tendency of offspring to use social cues:
      offspring of predator-exposed mothers were faster at copying a leader's behaviour
      towards the rewarded colour than offspring of unexposed mothers. However, once
      the colour-reward association had been learned, offspring of predator-exposed and
      unexposed mothers were equally able to generalize their learned association to a
      new foraging task. These results suggest that offspring of predator-exposed
      mothers might be able to overcome learning deficits caused by maternal stress by
      relying more on social cues.

PMID- 29046592
TI  - Natural variation in brain gene expression profiles of aggressive and
      nonaggressive individual sticklebacks.
AB  - Within many species, some individuals are consistently more aggressive than
      others. We examine whether there are differences in brain gene expression between
      aggressive versus nonaggressive behavioural types of individuals within a natural
      population of male three-spined sticklebacks (Gasterosteus aculeatus). We
      compared gene expression profiles of aggressive male sticklebacks to
      nonaggressive males in four regions of the brain (brainstem, cerebellum,
      diencephalon and telencephalon). Relatively few genes were differentially
      expressed between behavioural types in telencephalon, cerebellum and
      diencephalon, but hundreds of genes were differentially expressed in brainstem, a
      brain area involved in detecting threats. Six genes that were differentially
      expressed in response to a territorial intrusion in a previous study were also
      differentially expressed between behavioural types in this study, implying
      primarily non-shared but some shared molecular mechanisms. Our findings offer new
      insights into the molecular causes and correlates of behavioural plasticity and
      individual variation in behaviour.

PMID- 29046593
TI  - Wavelength-Selective Sequential Polymer Network Formation Controlled with a Two
      Color Responsive Initiation System.
AB  - We report a wavelength-selective polymerization process controlled by visible/UV
      light, whereby a base is generated for anion-mediated thiol-Michael
      polymerization reaction upon exposure at one wavelength (400-500 nm), while
      radicals are subsequently generated for a second stage radical polymerization at
      a second, independent wavelength (365 nm). Dual wavelength, light controlled
      sequential polymerization not only provides a relatively soft intermediate
      polymer that facilitates optimum processing and modification under visible light
      exposure but also enables a highly cross-linked, rigid final material after the
      UV-induced second stage radical polymerization. A photobase generator, NPPOC-TMG,
      and a photo-radical initiator, Irgacure 2959, were selected as the appropriate
      initiator pair for sequential thiol-Michael polymerization and acrylate
      homopolymerization. FT-IR and rheological tests were utilized to monitor the dual
      cure photo-polymerization process, and mechanical performance of the polymer was
      characterized at each distinct stage by dynamic mechanical analysis (DMA). By
      demonstrating complete light control in another sequential polymerization system
      (thiol-Michael and thiol-ene hybrid polymerization), this initiator pair exhibits
      great potential to regulate many other coupled anion and radical hybrid
      polymerizations in both a sequential and controllable manner.

PMID- 29046594
TI  - Framing in criminal investigation: How police officers (re)construct a crime.
AB  - Failures in criminal investigation may lead to wrongful convictions. Insight in
      the criminal investigation process is needed to understand how these
      investigative failures may rise and how measures can contribute to the prevention
      of this kind of failures. Some of the main findings of an empirical study of the
      criminal investigation process in four cases of major investigations are
      presented here. This criminal investigation process is analyzed as a process of
      framing, using Goffman's framing (Goffman, 1975) and interaction theories
      (Goffman, 1990). It shows that in addition to framing, other substantive and
      social factors affect the criminal investigation.

PMID- 29046595
TI  - Predictors of Individual Variation in Movement in a Natural Population of
      Threespine Stickleback (Gasterosteus aculeatus).
AB  - Species abundances and distributions are inherently tied to individuals'
      decisions about movement within their habitat. Therefore, integrating individual
      phenotypic variation within a larger ecological framework may provide better
      insight into how populations structure themselves. Recent evidence for consistent
      individual differences in behaviour prompts the hypothesis that variation in
      behavioural types might be related to variation in movement in natural
      environments. In a multiyear mark-recapture study, we found that individual
      sticklebacks exhibited consistent individual differences in behaviour both within
      a standardized testing arena designed to measure exploratory behaviour and within
      a river. Therefore, we asked whether individual differences in movement in a
      natural river were related to an individual's exploratory behavioural type. We
      also considered whether body condition and/or the individual's habitat or social
      environment use was related to movement. There was no evidence that an
      individual's exploratory behavioural type was related to movement within the
      river. Instead, an individual's habitat use and body condition interacted to
      influence natural movement patterns. Individuals in good condition were more
      likely to move further in the river, but only if they inhabited a vegetated
      complex part of the river; body condition had no influence on movement in those
      individuals inhabiting open areas of the river. Our results suggest that
      individual traits could help improve predictions about how populations may
      distribute themselves within patchy and complex environments.

PMID- 29046596
TI  - Birth Outcomes of Patients Enrolled in "Familias Sanas" Research project.
AB  - PURPOSE: This chapter examines birth outcomes of patients enrolled in Familias
      Sanas (Healthy Families), an educational intervention designed to reduce health
      disadvantages of low-income, immigrant Latvia mothers by providing social support
      during and after pregnancy. METHODOLOGY/APPROACH: Using a randomized control
      group design, the project recruited 440 pregnant Latina women, 88% of whom were
      first generation. Birth outcomes were collected through medical charts and
      analyzed using regression analysis to evaluate if there were any differences
      between patients enrolled in Familias Sanas compared to those patients who
      followed a typical prenatal course. FINDINGS: Control and intervention groups
      were found to be similar with regard to demographic characteristics. In addition,
      we did not observe a decrease in rate of a number of common pregnancy-related
      complications. Likewise, rates of operative delivery were similar between the two
      groups as were fetal weight at delivery and use of regional anesthesia at
      delivery. RESEARCH LIMITATIONS/IMPLICATIONS: The lack of improvements in birth
      outcomes for this study was perhaps because this social support intervention was
      not significant enough to override long-standing stressors such as socioeconomic
      status, poor nutrition, genetics, and other environmental stressors.
      ORIGINALITY/VALUE OF CHAPTER: This study was set in an inner-city, urban hospital
      with a large percentage of patients being of Hispanic descent. The study itself
      is a randomized controlled clinical trial, and data were collected directly from
      electronic medical records by physicians.

PMID- 29046597
TI  - Ultrasound tomography imaging with waveform sound speed: Parenchymal changes in
      women undergoing tamoxifen therapy.
AB  - Ultrasound tomography (UST) is an emerging modality that can offer quantitative
      measurements of breast density. Recent breakthroughs in UST image reconstruction
      involve the use of a waveform reconstruction as opposed to a ray-based
      reconstruction. The sound speed (SS) images that are created using the waveform
      reconstruction have a much higher image quality. These waveform images offer
      improved resolution and contrasts between regions of dense and fatty tissues. As
      part of a study that was designed to assess breast density changes using UST
      sound speed imaging among women undergoing tamoxifen therapy, UST waveform sound
      speed images were then reconstructed for a subset of participants. These initial
      results show that changes to the parenchymal tissue can more clearly be
      visualized when using the waveform sound speed images. Additional quantitative
      testing of the waveform images was also started to test the hypothesis that
      waveform sound speed images are a more robust measure of breast density than ray
      based reconstructions. Further analysis is still needed to better understand how
      tamoxifen affects breast tissue.

PMID- 29046599
TI  - We Know the Yin-But Where Is the Yang? Toward a Balanced Approach on Common
      Source Bias in Public Administration Scholarship.
AB  - Surveys have long been a dominant instrument for data collection in public
      administration. However, it has become widely accepted in the last decade that
      the usage of a self-reported instrument to measure both the independent and
      dependent variables results in common source bias (CSB). In turn, CSB is argued
      to inflate correlations between variables, resulting in biased findings.
      Subsequently, a narrow blinkered approach on the usage of surveys as single data
      source has emerged. In this article, we argue that this approach has resulted in
      an unbalanced perspective on CSB. We argue that claims on CSB are exaggerated,
      draw upon selective evidence, and project what should be tentative inferences as
      certainty over large domains of inquiry. We also discuss the perceptual nature of
      some variables and measurement validity concerns in using archival data. In
      conclusion, we present a flowchart that public administration scholars can use to
      analyze CSB concerns.

PMID- 29046598
TI  - Individual variation in foraging behavior reveals a trade-off between flexibility
      and performance of a top predator.
AB  - There is increasing evidence that behavioral flexibility is associated with the
      ability to adaptively respond to environmental change. Flexibility can be
      advantageous in some contexts such as exploiting novel resources, but it may come
      at a cost of accuracy or performance in ecologically relevant tasks, such as
      foraging. Such trade-offs may, in part, explain why individuals within a species
      are not equally flexible. Here, we conducted a reversal learning task and
      predation experiment on a top fish predator, the Northern pike (Esox lucius), to
      examine individual variation in flexibility and test the hypothesis that an
      individual's behavioral flexibility is negatively related with its foraging
      performance. Pikes were trained to receive a food reward from either a red or
      blue cup and then the color of the rewarded cup was reversed. We found that pike
      improved over time in how quickly they oriented to the rewarded cup, but there
      was a bias toward the color red. Moreover, there was substantial variation among
      individuals in their ability to overcome this red bias and switch from an
      unrewarded red cup to the rewarded blue cup, which we interpret as consistent
      variation among individuals in behavioral flexibility. Furthermore, individual
      differences in behavioral flexibility were negatively associated with foraging
      performance on ecologically relevant stickleback prey. Our data indicate that
      individuals cannot be both behaviorally flexible and efficient predators,
      suggesting a trade-off between these two traits.

PMID- 29046600
TI  - The Inside Out? Views of Young People, Parents, and Professionals Regarding
      Successful Secure Residential Care.
AB  - Although adolescents often seem to improve in their functioning during
      residential care, there still is little knowledge on what factors are important
      in achieving these changes. The present study aims to identify the care factors
      that are important for adolescents' behavior change during secure residential
      care. We conducted in-depth interviews with eight adolescents, their parents,
      eight group care workers and seven teachers concerning their in-care experiences.
      Both adolescents and parents commonly attributed changes during secure
      residential care to the treatment environment. Group care workers and teachers
      did not have a clear, consistent view on the treatment aspects causing positive
      change with the adolescents. According to the adolescents, good professionals
      apply a fine balance between rules and freedom, show empathy and are available
      for support. The view of parents corresponds to this image. Although group care
      workers are perceived as available for support, adolescents tend to make little
      use of this help if they experience personal problems during care. The results
      highlight the importance of responsiveness of secure residential care
      professionals to the needs and perspectives of adolescents and parents.

PMID- 29046601
TI  - Knowledge of practice: A multi-sited event ethnography of border security fairs
      in Europe and North America.
AB  - This article takes the reader inside four border security fairs in Europe and
      North America to examine the knowledge practices of border security
      professionals. Building on the border security as practice research agenda, the
      analysis focuses on the production, circulation, and consumption of scarce forms
      of knowledge. To explore situated knowledge of border security practices, I
      develop an approach to multi-sited event ethnography to observe and interpret
      knowledge that may be hard to access at the security fairs. The analysis focuses
      on mechanisms for disseminating and distributing scarce forms of knowledge,
      technological materializations of situated knowledge, expressions of transversal
      knowledge of security problems, how masculinities structure knowledge in gendered
      ways, and how unease is expressed through imagined futures in order to anticipate
      emergent solutions to proposed security problems. The article concludes by
      reflecting on the contradictions at play at fairs and how to address such
      contradictions through alternative knowledges and practices.

PMID- 29046602
TI  - Surveillance at sea: The transactional politics of border control in the Aegean.
AB  - The relationship between vision and action is a key element of both practices and
      conceptualizations of border surveillance in Europe. This article engages with
      what we call the 'operative vision' of surveillance at sea, specifically as
      performed by the border control apparatus in the Aegean. We analyse the political
      consequences of this operative vision by elaborating on three examples of
      fieldwork conducted in the Aegean and on the islands of Chios and Lesbos. One of
      the main aims is to bring the figure of the migrant back into the study of border
      technologies. By combining insights from science and technology studies with
      border, mobility and security studies, the article distinguishes between
      processes of intervention, mobilization and realization and emphasizes the role
      of migrants in their encounter with surveillance operations. Two claims are
      brought forward. First, engaging with recent scholarly work on the visual
      politics of border surveillance, we circumscribe an ongoing 'transactional
      politics'. Second, the dynamic interplay between vision and action brings about a
      situation of 'recalcitrance', in which mobile objects and subjects of various
      kinds are drawn into securitized relations, for instance in encounters between
      coast guard boats and migrant boats at sea. Without reducing migrants to
      epiphenomena of those relations, this recalcitrance typifies the objects of
      surveillance as both relatable as well as resistant, particularly in the tensions
      between border control and search and rescue.

PMID- 29046603
TI  - An extended data envelopment analysis for the decision-making.
AB  - Based on the CCR model, we propose an extended data envelopment analysis to
      evaluate the efficiency of decision making units with historical input and output
      data. The contributions of the work are threefold. First, the input and output
      data of the evaluated decision making unit are variable over time, and time
      series method is used to analyze and predict the data. Second, there are many
      sample decision making units, which are divided into several ordered sample
      standards in terms of production strategy, and the constraint condition consists
      of one of the sample standards. Furthermore, the efficiency is illustrated by
      considering the efficiency relationship between the evaluated decision making
      unit and sample decision making units from constraint condition. Third, to reduce
      the computation complexity, we introduce an algorithm based on the binary search
      tree in the model to choose the sample standard that has similar behavior with
      the evaluated decision making unit. Finally, we provide two numerical examples to
      illustrate the proposed model.

PMID- 29046604
TI  - Convergence rates in the law of large numbers for long-range dependent linear
      processes.
AB  - Baum and Katz (Trans. Am. Math. Soc. 120:108-123, 1965) obtained convergence
      rates in the Marcinkiewicz-Zygmund law of large numbers. Their result has already
      been extended to the short-range dependent linear processes by many authors. In
      this paper, we extend the result of Baum and Katz to the long-range dependent
      linear processes. As a corollary, we obtain convergence rates in the
      Marcinkiewicz-Zygmund law of large numbers for short-range dependent linear
      processes.

PMID- 29046605
TI  - Pseudo almost periodic solutions for shunting inhibitory cellular neural networks
      with continuously distributed delays.
AB  - The shunting inhibitory cellular neural networks with continuously distributed
      delays and pseudo almost periodic coefficients are considered. First, we make a
      generalization of the Halanay inequality, and then establish some sufficient
      conditions for the existence and asymptotical stability of pseudo almost periodic
      solutions. Finally, a numerical simulation is presented to illustrate the
      theoretical results.

PMID- 29046606
TI  - Prederivatives of gamma paraconvex set-valued maps and Pareto optimality
      conditions for set optimization problems.
AB  - Prederivatives play an important role in the research of set optimization
      problems. First, we establish several existence theorems of prederivatives for
      gamma-paraconvex set-valued mappings in Banach spaces with [Formula: see text].
      Then, in terms of prederivatives, we establish both necessary and sufficient
      conditions for the existence of Pareto minimal solution of set optimization
      problems.

PMID- 29046607
TI  - Exporting a Student-Centered Curriculum: A Home Institution's Perspective.
AB  - Numerous, mainly Anglo-Saxon, higher education institutions have agreements with
      foreign providers to deliver their curricula abroad. This trend is gradually
      making inroads into the medical domain, where foreign institutions undertake to
      offer their students learning experiences similar to those of the home
      institution. Not an easy feat, as the national health care contexts differ
      greatly between institutions. In a bid to export the curriculum, institutions
      risk compromising their financial resilience and reputation. This article
      presents an instrumental case study of a home institution's perspective on the
      establishment of a cross-border student-centered curriculum partnership. It
      provides the reader with a practical discourse on dimensions that need to be
      bridged between home and host contexts, and on new working processes that need to
      be integrated within the home institution's existing organizational structure. We
      describe the advantages and disadvantages based on our experiences with a
      centralized organizational approach, and advocate for a gradual move toward
      decentral interfaculty communities of practice.

PMID- 29046609
TI  - NPS and Online WOM: Investigating the Relationship Between Customers' Promoter
      Scores and eWOM Behavior.
AB  - The Net Promoter Score (NPS) is, according to Reichheld, the single most reliable
      indicator of company growth, and many companies use this recommendation-based
      technique for measuring customer loyalty. Despite its widespread adoption by many
      companies across multiple industries, the debate about NPS goes on. A major
      concern is that managers treat NPS as being equivalent across customers, which is
      often very misleading. By using a unique data set that combines customers'
      promoter scores and online word-of-mouth (eWOM) behavior, this research studies
      how individual customers' promoter scores are related to eWOM, including its
      relationship with the three categories of customers that are identified by the
      NPS paradigm (i.e., promoters, passives, and detractors). Based on a sample of
      189 customers, their promoter scores and corresponding eWOM, the results show
      that there is a positive relationship between customers' promoter scores and the
      valence of online messages. Further, while detractors and promoters are
      homogeneous with respect to the valence of the eWOM messages they spread,
      passives show message valence heterogeneity. Thus, although passives, the largest
      group of customers, have no weight in calculating the NPS, our results reveal
      that companies should flag passives for further attention and action.

PMID- 29046608
TI  - Elucidating the molecular basis of PPCD: Effects of decreased ZEB1 expression on
      corneal endothelial cell function.
AB  - PURPOSE: To investigate the functional role that the zinc e-box binding homeobox
      1 (ZEB1) gene, which underlies the genetic basis of posterior polymorphous
      corneal dystrophy 3 (PPCD3), plays in corneal endothelial cell proliferation,
      apoptosis, migration, and barrier function. METHODS: A human corneal endothelial
      cell line (HCEnC-21T) was transfected with siRNA targeting ZEB1 mRNA. Cell
      proliferation, apoptosis, migration, and barrier assays were performed: Cell
      proliferation was assessed with cell counting using a hemocytometer; cell
      apoptosis, induced by either ultraviolet C (UVC) radiation or doxorubicin
      treatment, was quantified by measuring cleaved caspase 3 (cCASP3) protein levels;
      and cell migration and barrier function were monitored with electric cell
      substrate impedance sensing (ECIS). RESULTS: ZEB1 knockdown in HCEnC-21T cells
      transfected with siRNA targeting ZEB1 did not result in a significant difference
      in cell proliferation when compared with control. Although knockdown of ZEB1 in
      HCEnC-21T cells sensitized the cells to UV-induced apoptosis, ZEB1 knockdown did
      not alter the cells' susceptibility to doxorubicin-induced apoptosis, as measured
      with cCASP3 protein levels, compared with controls. Similarly, no difference was
      observed in cell migration following ZEB1 knockdown. However, cell barrier
      function increased significantly following ZEB1 knockdown. CONCLUSIONS: The
      corneal endothelium in PPCD3 is characterized by morphologic, anatomic, and
      molecular features that are more consistent with an epithelial-like rather than
      an endothelial-like phenotype. Although these characteristics have been well
      documented, we demonstrate for the first time that susceptibility to UV-induced
      apoptosis and cell barrier function are significantly altered in the setting of
      reduced ZEB1. The significance of an altered cellular response to apoptotic
      stimuli and increased cell barrier function in the pathobiology of PPCD remains
      to be fully elucidated.

PMID- 29046610
TI  - Molecular epidemiology of mosquitoes for the transmission of forest malaria in
      south-central Vietnam.
AB  - Human infection caused by non-human primate malarial parasites, such as
      Plasmodium knowlesi and Plasmodium cynomolgi, occurs naturally in Southeast Asian
      countries, including Vietnam. Members of the Anopheles dirus species complex are
      known to be important vectors of human malarial parasites in the forested areas
      of southern and central Vietnam, including those in Khanh Phu commune and Khanh
      Hoa Province. Recent molecular epidemiological studies in Vietnam have reported
      cases of co-infection with Plasmodium falciparum, Plasmodium vivax, Plasmodium
      malariae, and P. knowlesi in An. dirus. The commonly found macaques in the forest
      in the forested areas are suspected to be bitten by the same An. dirus population
      that bites humans. A recent epidemiological study identified six species of
      malarial parasites in sporozoite-infected An. dirus using polymerase chain
      reaction, of which P. vivax was the most common, followed by P. knowlesi,
      Plasmodium inui, P. cynomolgi, Plasmodium coatneyi, and P. falciparum. Based on a
      gametocyte analysis, the same allelic gametocyte types were observed in both
      humans and mosquitoes at similar frequencies. These observations suggest that
      people who stay overnight in the forests are frequently infected with both human
      and non-human primate malarial parasites, leading to the emergence of novel
      zoonotic malaria. Moreover, it is suggested that mosquito vector populations
      should be controlled and monitored closely.

PMID- 29046611
TI  - Variation in chemical, colloidal and electrochemical properties of carbon
      nanotubes with the degree of carboxylation.
AB  - Multiwalled carbon nanotubes (CNTs) were carboxylated via microwave irradiation
      where the treatment time was varied to alter the degree of functionalization, and
      as many as one in 15 carbons in the CNT could be oxidized. Chemical, physical,
      electrochemical, and colloidal behavior of the carboxylated CNTs was studied. All
      properties changed with the degree of functionalization to a point beyond which
      they appeared to remain constant. The surface area increased from 173.9 to 270.9
      m2/g while the critical coagulation concentration (CCC) values increased from
      142.14 to 168.69 mM in the presence of NaCl, and the corresponding increase was
      from 0.97 to 5.32 mM in the presence of MgCl2. As seen from cyclic voltammetry
      curves, the functionalized CNTs showed mainly non-Faradic interactions with
      Na2SO4, but showed Faradic behaviors in alkaline KOH.

PMID- 29046613
TI  - Ecologies of ideologies: Explaining party entry and exit in West-European
      parliaments, 1945-2013.
AB  - This study introduces a population-ecological approach to the entry and exit of
      political parties. A primary proposition of population ecology is that
      organizational entry and exit depends on the number of organizations already
      present: that is, density. We propose that political parties mainly experience
      competition from parties in the same ideological niche (left, centre, right).
      Pooled time-series analyses of 410 parties, 263 elections and 18 West-European
      countries largely support our expectations. We find that political parties are
      more likely to exit when density within their niche increases. Also there is
      competition between adjacent ideological niches, i.e. between centrist and right
      wing niches. In contrast to our expectations, neither density nor institutional
      rules impact party entry. This raises important questions about the rationale of
      prospective entrants.

PMID- 29046612
TI  - Space, race, and poverty: Spatial inequalities in walkable neighborhood
      amenities?
AB  - BACKGROUND: Multiple and varied benefits have been suggested for increased
      neighborhood walkability. However, spatial inequalities in neighborhood
      walkability likely exist and may be attributable, in part, to residential
      segregation. OBJECTIVE: Utilizing a spatial demographic perspective, we evaluated
      potential spatial inequalities in walkable neighborhood amenities across census
      tracts in Boston, MA (US). METHODS: The independent variables included minority
      racial/ethnic population percentages and percent of families in poverty. Walkable
      neighborhood amenities were assessed with a composite measure. Spatial
      autocorrelation in key study variables were first calculated with the Global
      Moran's I statistic. Then, Spearman correlations between neighborhood socio
      demographic characteristics and walkable neighborhood amenities were calculated
      as well as Spearman correlations accounting for spatial autocorrelation. We fit
      ordinary least squares (OLS) regression and spatial autoregressive models, when
      appropriate, as a final step. RESULTS: Significant positive spatial
      autocorrelation was found in neighborhood socio-demographic characteristics (e.g.
      census tract percent Black), but not walkable neighborhood amenities or in the
      OLS regression residuals. Spearman correlations between neighborhood socio
      demographic characteristics and walkable neighborhood amenities were not
      statistically significant, nor were neighborhood socio-demographic
      characteristics significantly associated with walkable neighborhood amenities in
      OLS regression models. CONCLUSIONS: Our results suggest that there is residential
      segregation in Boston and that spatial inequalities do not necessarily show up
      using a composite measure. COMMENTS: Future research in other geographic areas
      (including international contexts) and using different definitions of
      neighborhoods (including small-area definitions) should evaluate if spatial
      inequalities are found using composite measures but also should use measures of
      specific neighborhood amenities.

PMID- 29046614
TI  - Long-term effects of nurse-led individualized education on middle-aged patients
      with acute coronary synrome: a quasi-experimental study.
AB  - BACKGROUND: This study examined the long-term effects of nurse-led,
      individualized education on self-efficacy, self-care compliance, and health
      related quality of life (HRQoL) in middle-aged patients with new-onset acute
      coronary syndrome. METHODS: A quasi-experimental pretest-posttest design was used
      in the study. A cardiovascular nurse provided individualized education to the
      intervention group (n = 32), and self-efficacy, self-care compliance, and HRQoL
      at baseline and 3 and 12 months after discharge were compared to those of a
      control group (n = 30). Patients were recruited from a cardiovascular care unit
      at a university hospital between 2012 and 2013. Repeated measures analysis of
      variance was used to compare time-related changes. RESULTS: There was no
      significant difference in self-efficacy between the 2 groups over a fixed period
      (F = 3.47, p = 0.067) and showed no interaction between the 2 groups (F = 0.45, p
      = 0.636). However, significant differences were found in the main and interaction
      effects between the 2 groups and changes in self-care compliance over the follow
      up period differed significantly between the 2 groups (F = 28.72, p < 0.001).
      Changes in mental HRQoL over the follow-up period differed significantly between
      the 2 groups (F = 33.34, p < 0.001) and significant interaction effect (F = 4.40,
      p = 0.040). CONCLUSIONS: Structured nurse-led education should be provided to
      middle-aged patients with new-onset acute coronary syndrome, as part of routine
      predischarge education, to increase self-care compliance and mental HRQoL and
      prevent secondary adverse events. TRIAL REGISTRATION: Trial registration number
      (TRN) is KCT0002454. The study was registered retrospectively with registration
      date July 9, 2017.

PMID- 29046615
TI  - Integrated genomic characterization of cancer genes in glioma.
AB  - BACKGROUND: Cancers are caused by the acquisition of somatic mutations. Numerous
      efforts have been made to characterize the key driver genes and pathways in
      glioma, however, the etiology of glioma is still not completely known. This study
      was implemented to characterize driver genes in glioma independently of somatic
      mutation frequencies. METHODS: Driver genes and pathways were predicted by
      OncodriveCLUST, OncodriveFM, Icages, Drgap and Dendrix in glioma using 31,958
      somatic mutations from TCGA, followed by an integrative characterization of
      driver genes. RESULTS: Overall, 685 driver genes and 215 driver pathways were
      determined by the five tools. FSTL5, HCN1, TMEM132D, TRHDE and KRT222 showed the
      strongest expression correlation with other genes in the co-expression network of
      glioma tissues. ST6GAL2, PIK3CA, PIK3R1, TP53 and EGFR are at the core of the
      protein-protein interaction network. 133 driver genes were up-regulated and
      associated to poor prognosis, 43 driver genes were down-regulated and related to
      favorable clinical outcome in glioma patients. The driver genes such as MSH6 and
      RUNX1T1 might serve as candidate prognostic biomarkers and therapeutic targets in
      glioma. CONCLUSIONS: The set of new cancer genes and pathways sheds insights into
      the tumorigenesis of glioma and paves the way for developing driver gene-targeted
      therapy and prognostic biomarkers in glioma.

PMID- 29046616
TI  - Comparison of three different anti-Xa assays in major orthopedic surgery patients
      treated with direct oral anticoagulant.
AB  - BACKGROUND: Measurement of edoxaban plasma concentration has been gathering
      attention in major orthopedic surgery patients receiving edoxaban for the
      prevention of venous thromboembolism (VTE). METHODS: The anti-Xa activity was
      measured one hour after edoxaban intake using 3 different assays in 200 patients
      after major orthopedic surgery. RESULTS: The anti-Xa activities on Day 8 were
      significantly higher than those on Day 4 and those on Day 4 were significantly
      higher than those on Day 1. The anti-Xa activities in two assays closely
      correlated with each other, but the other anti-Xa assay did not correlated with
      other two assays. The anti-Xa activities as detected in the three Xa assays were
      significantly higher in the patients without deep vein thrombosis (DVT) than in
      those with DVT on Day 4. Additionally, there were no significant differences in
      the anti-Xa activities of assays A, B and C between patients with and without
      massive bleeding (MB) on Days 1, 4, 8 and 15. CONCLUSION: The results of this
      study suggest that anti-Xa level could be predictive of the risk of VTE, but not
      of the risk of massive bleeding.

PMID- 29046617
TI  - A fluorescence in situ hybridization (FISH) protocol for stickleback tissue.
AB  - BACKGROUND: Threespine stickleback are an important model for behaviour and
      evolutionary studies. A growing number of quantitative trait loci (QTL) and gene
      expression studies are identifying genes related to ecologically important traits
      in sticklebacks. In order to visualize the expression of candidate genes, we
      developed a fluorescence in situ hybridization (FISH) protocol. METHODS: We
      present a protocol for FISH on fresh or flash-frozen dissected tissue, using
      either cryo- or paraffin embedding. The protocol covers probe design guidelines
      and synthesis, sample embedding, sectioning, and the hybridization process. The
      protocol is optimized for brain tissue. Key steps for modifying the protocol for
      other tissues are noted. RESULTS: The FISH protocol resulted in specific
      labelling under all combinations of dissection and embedding conditions. Paraffin
      embedding preserved morphology better than cryo-embedding. We provide
      representative results showing the expression of glial fibrillary acidic protein
      (GFAP), oxytocin receptor (OXTR), and tyrosine hydroxylase (TH) in the brain.

PMID- 29046618
TI  - MESOSCOPIC MODELING OF STOCHASTIC REACTION-DIFFUSION KINETICS IN THE SUBDIFFUSIVE
      REGIME.
AB  - Subdiffusion has been proposed as an explanation of various kinetic phenomena
      inside living cells. In order to fascilitate large-scale computational studies of
      subdiffusive chemical processes, we extend a recently suggested mesoscopic model
      of subdiffusion into an accurate and consistent reaction-subdiffusion
      computational framework. Two different possible models of chemical reaction are
      revealed and some basic dynamic properties are derived. In certain cases those
      mesoscopic models have a direct interpretation at the macroscopic level as
      fractional partial differential equations in a bounded time interval. Through
      analysis and numerical experiments we estimate the macroscopic effects of
      reactions under subdiffusive mixing. The models display properties observed also
      in experiments: for a short time interval the behavior of the diffusion and the
      reaction is ordinary, in an intermediate interval the behavior is anomalous, and
      at long times the behavior is ordinary again.

PMID- 29046619
TI  - EIGENVECTOR-BASED CENTRALITY MEASURES FOR TEMPORAL NETWORKS.
AB  - Numerous centrality measures have been developed to quantify the importances of
      nodes in time-independent networks, and many of them can be expressed as the
      leading eigenvector of some matrix. With the increasing availability of network
      data that changes in time, it is important to extend such eigenvector-based
      centrality measures to time-dependent networks. In this paper, we introduce a
      principled generalization of network centrality measures that is valid for any
      eigenvector-based centrality. We consider a temporal network with N nodes as a
      sequence of T layers that describe the network during different time windows, and
      we couple centrality matrices for the layers into a supra-centrality matrix of
      size NT * NT whose dominant eigenvector gives the centrality of each node i at
      each time t. We refer to this eigenvector and its components as a joint
      centrality, as it reflects the importances of both the node i and the time layer
      t. We also introduce the concepts of marginal and conditional centralities, which
      facilitate the study of centrality trajectories over time. We find that the
      strength of coupling between layers is important for determining multiscale
      properties of centrality, such as localization phenomena and the time scale of
      centrality changes. In the strong-coupling regime, we derive expressions for time
      averaged centralities, which are given by the zeroth-order terms of a singular
      perturbation expansion. We also study first-order terms to obtain first-order
      mover scores, which concisely describe the magnitude of nodes' centrality changes
      over time. As examples, we apply our method to three empirical temporal networks:
      the United States Ph.D. exchange in mathematics, costarring relationships among
      top-billed actors during the Golden Age of Hollywood, and citations of decisions
      from the United States Supreme Court.

PMID- 29046621
TI  - Applying a statistical method in transvaginal ultrasound training: lessons from
      the learning curve cumulative summation test (LC-CUSUM) for endometriosis
      mapping.
AB  - BACKGROUND: Methods available for assessing the learning curve, such as a
      predefined number of procedures or direct mentoring are lacking. Our aim was to
      describe the use of a statistical method to identify the minimal training length
      of an experienced sonographer, newly trained in deep infiltrating endometriosis
      (DIE) mapping by evaluating the learning curve of transvaginal ultrasound (TVUS)
      in the preoperative assessment of endometriosis. METHODS: A retrospective study
      in a tertiary referral center for endometriosis. Reports and stored data from
      TVUS scans performed by one operator with training in general gynecological
      ultrasound, but not in endometriosis mapping, were analyzed retrospectively for
      patients who subsequently underwent laparoscopy, which served as a reference
      standard. The performance of TVUS was assessed for the following sites:
      endometriomas, bladder, vagina, pouch of Douglas, bowel and uterosacral
      ligaments, and correlated with laparoscopic findings. Sensitivity, specificity,
      PPV, NPV, and accuracy were calculated, and the operator's diagnostic performance
      was assessed using the learning curve cumulative summation test (LC-CUSUM).
      RESULTS: Data from 94 women were available for analysis. The learning curve using
      the LC-CUSUM graph showed that the sonographer reached the predefined level of
      proficiency in detecting endometriosis lesions after 20, 26, 32, 31, 38, and 44
      examinations for endometriomas, bladder nodules, vaginal nodules, pouch of
      Douglas obliteration, bowel nodules, and uterosacral ligament nodules,
      respectively. CONCLUSIONS: LC-CUSUM allows monitoring of individual performance
      during the learning process of new methodologies. This study shows that a
      sonographer trained in general gynecologic ultrasonography, who devotes time to
      learn TVUS for DIE mapping, can achieve proficiency for diagnosing the major
      types of endometriotic lesions after examining less than 50 patients who
      subsequently undergo surgery in a training setting.

PMID- 29046622
TI  - Essure(r) present controversies and 5 years' learned lessons: a retrospective
      study with short- and long-term follow-up.
AB  - BACKGROUND: The risk-benefit of contraception with Essure(r) is being readdressed
      due to an increase of reports of adverse effects with this device. Our aim was to
      proceed to an internal quality evaluation and to identify opportunities for
      protocol improvement. We proceeded to a one-center, retrospective consecutive
      case series of women admitted for Essure(r) placement, from 1 January 2012 until
      31 December 2016 (5 years). RESULTS: In a total of 274 women, technical
      difficulties were mainly unilateral, with no acute or short-term severe
      complications. The procedure was brief (median 3.2 min, IQR 2.5-5.2) and
      moderately painful (median of 4 in a 0-10 scale; IQR 3-5). At 3 months, the
      failure rate was 2%, with no pregnancies. Second surgery indication (< 1%)
      resumed to a case of nickel hypersensitivity. At 1 year, pregnancy rate was 1%.
      Ninety-eight percent of the patients would recommend the method. CONCLUSIONS: We
      identified high patient satisfaction and low failure rates, both at short and
      long term. Investigation about whether some women still have patent tubes at the
      3-month follow-up could lead to protocol improvement. It is important that
      clinicians look for second causes for adverse effects related to Essure(r) and
      avoid the erroneous indication for implant removal. Long follow-up allowed for
      both internal quality evaluation and clarification of misconception; it could
      possibly also have contributed to patient satisfaction.

PMID- 29046620
TI  - The dental calculus metabolome in modern and historic samples.
AB  - INTRODUCTION: Dental calculus is a mineralized microbial dental plaque biofilm
      that forms throughout life by precipitation of salivary calcium salts. Successive
      cycles of dental plaque growth and calcification make it an unusually well
      preserved, long-term record of host-microbial interaction in the archaeological
      record. Recent studies have confirmed the survival of authentic ancient DNA and
      proteins within historic and prehistoric dental calculus, making it a promising
      substrate for investigating oral microbiome evolution via direct measurement and
      comparison of modern and ancient specimens. OBJECTIVE: We present the first
      comprehensive characterization of the human dental calculus metabolome using a
      multi-platform approach. METHODS: Ultra performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic
      (200 years old) dental calculus, including metabolites of drug and dietary
      origin. A subset of historic samples was additionally analyzed by high-resolution
      gas chromatography-MS (GC-MS) and UPLC-MS/MS for further characterization of
      metabolites and lipids. Metabolite profiles of modern and historic calculus were
      compared to identify patterns of persistence and loss. RESULTS: Dipeptides, free
      amino acids, free nucleotides, and carbohydrates substantially decrease in
      abundance and ubiquity in archaeological samples, with some exceptions. Lipids
      generally persist, and saturated and mono-unsaturated medium and long chain fatty
      acids appear to be well-preserved, while metabolic derivatives related to
      oxidation and chemical degradation are found at higher levels in archaeological
      dental calculus than fresh samples. CONCLUSIONS: The results of this study
      indicate that certain metabolite classes have higher potential for recovery over
      long time scales and may serve as appropriate targets for oral microbiome
      evolutionary studies.

PMID- 29046623
TI  - Biocompatible D-A Semiconducting Polymer Nanoparticle with Light-Harvesting Unit
      for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy.
AB  - The development of nanotheranostic agents that integrate diagnosis and therapy
      for effective personalized precision medicine has obtained tremendous attention
      in the past few decades. In this report, biocompatible electron donor-acceptor
      conjugated semiconducting polymer nanoparticles (PPor-PEG NPs) with light
      harvesting unit is prepared and developed for highly effective photoacoustic
      imaging guided photothermal therapy. To the best of our knowledge, it is the
      first time that the concept of light-harvesting unit is exploited for enhancing
      the photoacoustic signal and photothermal energy conversion in polymer-based
      theranostic agent. Combined with additional merits including donor-acceptor pair
      to favor electron transfer and fluorescence quenching effect after NP formation,
      the photothermal conversion efficiency of the PPor-PEG NPs is determined to be
      62.3%, which is the highest value among reported polymer NPs. Moreover, the as
      prepared PPor-PEG NP not only exhibits a remarkable cell-killing ability but also
      achieves 100% tumor elimination, demonstrating its excellent photothermal
      therapeutic efficacy. Finally, the as-prepared water-dispersible PPor-PEG NPs
      show good biocompatibility and biosafety, making them a promising candidate for
      future clinical applications in cancer theranostics.

PMID- 29046624
TI  - Designing Thin, Ultrastretchable Electronics with Stacked Circuits and
      Elastomeric Encapsulation Materials.
AB  - Many recently developed soft, skin-like electronics with high performance
      circuits and low modulus encapsulation materials can accommodate large bending,
      stretching, and twisting deformations. Their compliant mechanics also allows for
      intimate, nonintrusive integration to the curvilinear surfaces of soft biological
      tissues. By introducing a stacked circuit construct, the functional density of
      these systems can be greatly improved, yet their desirable mechanics may be
      compromised due to the increased overall thickness. To address this issue, the
      results presented here establish design guidelines for optimizing the deformable
      properties of stretchable electronics with stacked circuit layers. The effects of
      three contributing factors (i.e., the silicone inter-layer, the composite
      encapsulation, and the deformable interconnects) on the stretchability of a
      multilayer system are explored in detail via combined experimental observation,
      finite element modeling, and theoretical analysis. Finally, an electronic module
      with optimized design is demonstrated. This highly deformable system can be
      repetitively folded, twisted, or stretched without observable influences to its
      electrical functionality. The ultrasoft, thin nature of the module makes it
      suitable for conformal biointegration.

PMID- 29046625
TI  - Assessing the Depth of Cognitive Processing as the Basis for Potential User-State
      Adaptation.
AB  - Objective: Decoding neurocognitive processes on a single-trial basis with Brain
      Computer Interface (BCI) techniques can reveal the user's internal interpretation
      of the current situation. Such information can potentially be exploited to make
      devices and interfaces more user aware. In this line of research, we took a
      further step by studying neural correlates of different levels of cognitive
      processes and developing a method that allows to quantify how deeply presented
      information is processed in the brain. Methods/Approach: Seventeen participants
      took part in an EEG study in which we evaluated different levels of cognitive
      processing (no processing, shallow, and deep processing) within three distinct
      domains (memory, language, and visual imagination). Our investigations showed
      gradual differences in the amplitudes of event-related potentials (ERPs) and in
      the extend and duration of event-related desynchronization (ERD) which both
      correlate with task difficulty. We performed multi-modal classification to map
      the measured correlates of neurocognitive processing to the corresponding level
      of processing. Results: Successful classification of the neural components was
      achieved, which reflects the level of cognitive processing performed by the
      participants. The results show performances above chance level for each
      participant and a mean performance of 70-90% for all conditions and
      classification pairs. Significance: The successful estimation of the level of
      cognition on a single-trial basis supports the feasibility of user-state
      adaptation based on ongoing neural activity. There is a variety of potential use
      cases such as: a user-friendly adaptive design of an interface or the development
      of assistance systems in safety critical workplaces.

PMID- 29046626
TI  - Curcumin Activates AMPK Pathway and Regulates Lipid Metabolism in Rats Following
      Prolonged Clozapine Exposure.
AB  - Clozapine (CLO) remains an ultimate option for patients with treatment resistant
      schizophrenia. However, the atypical antipsychotic is often associated with
      serious metabolic side effects, such as dyslipidemia. Hepatic sterol regulatory
      element-binding proteins (SREBPs) are central in the allosteric control of a
      variety of lipid biosynthetic pathways. There is emerging evidence that CLO can
      activate SREBP pathway and enhance downstream lipogenesis, whereas curcumin
      (CUR), a major active compound of Curcuma longa, contains hypolipidemic
      properties. Therefore, in the present study, we examined the protective effects
      of CUR against CLO-induced lipid disturbance and analyzed the expression of key
      components in hepatic lipid metabolism. Our data showed that 4-week treatment of
      CLO (15 mg/kg/day) markedly elevated serum lipid levels and resulted in hepatic
      lipid accumulation, whereas co-treatment of CUR (80 mg/kg/day) alleviated the CLO
      induced dyslipidemia. We further demonstrated that CUR appears to be a novel AMP
      activated protein kinase (AMPK) agonist, which enhanced AMPK phosphorylation and
      mitigated CLO-induced SREBP overexpression. Additionally, CUR also modulated the
      downstream SREBP-targeted genes involved in fatty acid synthesis and cholesterol
      metabolism, including fatty acid synthase (FAS) and HMG-CoA reductase (HMGCR). In
      summary, our study suggests that the suppressed AMPK activity and thereby
      enhanced SREBP-dependent lipid synthesis could be associated with the
      antipsychotic-stimulated dyslipidemia, whereas CUR may maintain lipid homeostasis
      by directly binding to AMPK, indicating that adjunctive use of CUR could be a
      promising preventive strategy for the drug-induced lipogenesis.

PMID- 29046628
TI  - The Human Periallocortex: Layer Pattern in Presubiculum, Parasubiculum and
      Entorhinal Cortex. A Review.
AB  - The cortical mantle is not homogeneous, so that three types of cortex can be
      distinguished: allocortex, periallocortex and isocortex. The main distinction
      among those three types is based on morphological differences, in particular the
      number of layers, overall organization, appearance, etc., as well as its
      connectivity. Additionally, in the phylogenetic scale, this classification is
      conserved among different mammals. The most primitive and simple cortex is the
      allocortex, which is characterized by the presence of three layers, with one
      cellular main layer; it is continued by the periallocortex, which presents six
      layers, although with enough differences in the layer pattern to separate three
      different fields: presubiculum (PrS), parasubiculum (PaS), and entorhinal cortex
      (EC). The closest part to the allocortex (represented by the subiculum) is the
      PrS, which shows outer (layers I-III) and inner (V-VI) principal layers (lamina
      principalis externa and lamina principalis interna), both separated by a cell
      poor band, parallel to the pial surface (layer IV or lamina dissecans). This
      layer organization is present throughout the anterior-posterior axis. The PaS
      continues the PrS, but its rostrocaudal extent is shorter than the PrS. The
      organization of the PaS shows the layer pattern more clearly than in the PrS. Up
      to six layers are recognizable in the PaS, with layer IV as lamina dissecans
      between superficial (layers I-III) and deep (V-VI) layers, as in the PrS. The EC
      presents even more clearly the layer pattern along both mediolateral and
      rostrocaudal extent. The layer pattern is a thick layer I, layer II in islands,
      layer III medium pyramids, layer IV as lamina dissecans (not present throughout
      the EC extent), layer V with dark and big pyramids and a multiform layer VI. The
      EC borders laterally the proisocortex (incomplete type of isocortex). Variations
      in the appearance of its layers justify the distinction of subfields in the EC,
      in particular in human and nonhuman primates. EC layers are not similar to those
      in the neocortex. The transition between the periallocortical EC and isocortex is
      not sharp, so that the proisocortex forms an intervening cortex, which fills the
      gap between the periallocortex and the isocortex.

PMID- 29046627
TI  - MeCP2 Deficiency in Neuroglia: New Progress in the Pathogenesis of Rett Syndrome.
AB  - Rett syndrome (RTT) is an X-linked neurodevelopmental disease predominantly
      caused by mutations of the methyl-CpG-binding protein 2 (MeCP2) gene. Generally,
      RTT has been attributed to neuron-centric dysfunction. However, increasing
      evidence has shown that glial abnormalities are also involved in the pathogenesis
      of RTT. Mice that are MeCP2-null specifically in glial cells showed similar
      behavioral and/or neuronal abnormalities as those found in MeCP2-null mice, a
      mouse model of RTT. MeCP2 deficiency in astrocytes impacts the expression of
      glial intermediate filament proteins such as fibrillary acidic protein (GFAP) and
      S100 and induces neuron toxicity by disturbing glutamate metabolism or enhancing
      microtubule instability. MeCP2 deficiency in oligodendrocytes (OLs) results in
      down-regulation of myelin gene expression and impacts myelination. While MeCP2
      deficient microglia cells fail in response to environmental stimuli, release
      excessive glutamate, and aggravate impairment of the neuronal circuit. In this
      review, we mainly focus on the progress in determining the role of MeCP2 in glial
      cells involved in RTT, which may provide further insight into a therapeutic
      intervention for RTT.

PMID- 29046629
TI  - Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from
      the Embryonic Mid-Hindbrain Region.
AB  - Reduced fibroblast growth factor (FGF) signaling from the mid-hindbrain or
      isthmus organizer (IsO) during early embryonic development results in hypoplasia
      of the midbrain and cerebellar vermis. We previously reported evidence for
      reduced Fgf8 expression and FGF signaling in the mid-hindbrain region of embryos
      heterozygous for Chd7, the gene mutated in CHARGE (Coloboma, Heart defects,
      choanal Atresia, Retarded growth and development, Genitourinary anomalies and Ear
      defects) syndrome. However, Chd7+/- animals only exhibit mild cerebellar vermis
      anomalies. As homozygous deletion of Chd7 is embryonic lethal, we conditionally
      deleted Chd7 from the early embryonic mid-hindbrain region to identify the
      function of CHD7 in mid-hindbrain development. Using a combination of high
      resolution structural MRI and histology, we report striking midbrain and
      cerebellar vermis hypoplasia in the homozygous conditional mutants. We show that
      cerebellar vermis hypoplasia is associated with reduced embryonic Fgf8 expression
      and an expanded roof plate in rhombomere 1 (r1). These findings identify an
      essential role for Chd7 in regulating mid-hindbrain development via Fgf8.

PMID- 29046630
TI  - Agency over Phantom Limb Enhanced by Short-Term Mirror Therapy.
AB  - Most amputees experience phantom limb, whereby they feel that the amputated limb
      is still present. In some cases, these experiences include pain that can be
      alleviated by "mirror therapy." Mirror therapy consists of superimposing a
      mirrored image of the moving intact limb onto the phantom limb. This therapy
      provides a closed loop between the motor command to the amputated limb and its
      predicted visual feedback. This loop is also involved in the sense of agency, a
      feeling of controlling one's own body. However, it is unclear how mirror therapy
      is related to the sense of agency over a phantom limb. Using mirror therapy, we
      investigated phantom limb pain and the senses of agency and ownership (i.e., a
      feeling of having one's own body) of the phantom limb. Nine upper-limb amputees,
      five of whom reported recent phantom limb pain, underwent a single 15-min trial
      of mirror therapy. Before and after the trial, the participants completed a
      questionnaire regarding agency, ownership, and pain related to their phantom
      limb. They reported that the sense of agency over the phantom limb increased
      following the mirror therapy trial, while the ownership slightly increased but
      not as much as did the agency. The reported pain did not change; that is, it was
      comparably mild before and after the trial. These results suggest that short-term
      mirror therapy can, at least transiently, selectively enhance the sense of agency
      over a phantom limb, but may not alleviate phantom limb pain.

PMID- 29046631
TI  - Development of a Bayesian Estimator for Audio-Visual Integration: A
      Neurocomputational Study.
AB  - The brain integrates information from different sensory modalities to generate a
      coherent and accurate percept of external events. Several experimental studies
      suggest that this integration follows the principle of Bayesian estimate.
      However, the neural mechanisms responsible for this behavior, and its development
      in a multisensory environment, are still insufficiently understood. We recently
      presented a neural network model of audio-visual integration (Neural Computation,
      2017) to investigate how a Bayesian estimator can spontaneously develop from the
      statistics of external stimuli. Model assumes the presence of two unimodal areas
      (auditory and visual) topologically organized. Neurons in each area receive an
      input from the external environment, computed as the inner product of the sensory
      specific stimulus and the receptive field synapses, and a cross-modal input from
      neurons of the other modality. Based on sensory experience, synapses were trained
      via Hebbian potentiation and a decay term. Aim of this work is to improve the
      previous model, including a more realistic distribution of visual stimuli: visual
      stimuli have a higher spatial accuracy at the central azimuthal coordinate and a
      lower accuracy at the periphery. Moreover, their prior probability is higher at
      the center, and decreases toward the periphery. Simulations show that, after
      training, the receptive fields of visual and auditory neurons shrink to reproduce
      the accuracy of the input (both at the center and at the periphery in the visual
      case), thus realizing the likelihood estimate of unimodal spatial position.
      Moreover, the preferred positions of visual neurons contract toward the center,
      thus encoding the prior probability of the visual input. Finally, a prior
      probability of the co-occurrence of audio-visual stimuli is encoded in the cross
      modal synapses. The model is able to simulate the main properties of a Bayesian
      estimator and to reproduce behavioral data in all conditions examined. In
      particular, in unisensory conditions the visual estimates exhibit a bias toward
      the fovea, which increases with the level of noise. In cross modal conditions,
      the SD of the estimates decreases when using congruent audio-visual stimuli, and
      a ventriloquism effect becomes evident in case of spatially disparate stimuli.
      Moreover, the ventriloquism decreases with the eccentricity.

PMID- 29046632
TI  - A Developmental Learning Approach of Mobile Manipulator via Playing.
AB  - Inspired by infant development theories, a robotic developmental model combined
      with game elements is proposed in this paper. This model does not require the
      definition of specific developmental goals for the robot, but the developmental
      goals are implied in the goals of a series of game tasks. The games are
      characterized into a sequence of game modes based on the complexity of the game
      tasks from simple to complex, and the task complexity is determined by the
      applications of developmental constraints. Given a current mode, the robot
      switches to play in a more complicated game mode when it cannot find any new
      salient stimuli in the current mode. By doing so, the robot gradually achieves it
      developmental goals by playing different modes of games. In the experiment, the
      game was instantiated into a mobile robot with the playing task of picking up
      toys, and the game is designed with a simple game mode and a complex game mode. A
      developmental algorithm, "Lift-Constraint, Act and Saturate," is employed to
      drive the mobile robot move from the simple mode to the complex one. The
      experimental results show that the mobile manipulator is able to successfully
      learn the mobile grasping ability after playing simple and complex games, which
      is promising in developing robotic abilities to solve complex tasks using games.

PMID- 29046633
TI  - Activity-Dependent Phosphorylation by CaMKIIdelta Alters the Ca2+ Affinity of the
      Multi-C2-Domain Protein Otoferlin.
AB  - Otoferlin is essential for fast Ca2+-triggered transmitter release from auditory
      inner hair cells (IHCs), playing key roles in synaptic vesicle release,
      replenishment and retrieval. Dysfunction of otoferlin results in profound
      prelingual deafness. Despite its crucial role in cochlear synaptic processes,
      mechanisms regulating otoferlin activity have not been studied to date. Here, we
      identified Ca2+/calmodulin-dependent serine/threonine kinase II delta
      (CaMKIIdelta) as an otoferlin binding partner by pull-downs from chicken utricles
      and reassured interaction by a co-immunoprecipitation with heterologously
      expressed proteins in HEK cells. We confirmed the expression of CaMKIIdelta in
      rodent IHCs by immunohistochemistry and real-time PCR. A proximity ligation assay
      indicates close proximity of the two proteins in rat IHCs, suggesting that
      otoferlin and CaMKIIdelta also interact in mammalian IHCs. In vitro
      phosphorylation of otoferlin by CaMKIIdelta revealed ten phosphorylation sites,
      five of which are located within C2-domains. Exchange of serines/threonines at
      phosphorylated sites into phosphomimetic aspartates reduces the Ca2+ affinity of
      the recombinant C2F domain 10-fold, and increases the Ca2+ affinity of the C2C
      domain. Concordantly, we show that phosphorylation of otoferlin and/or its
      interaction partners are enhanced upon hair cell depolarization and blocked by
      pharmacological CaMKII inhibition. We therefore propose that otoferlin activity
      is regulated by CaMKIIdelta in IHCs.

PMID- 29046634
TI  - Cognitive Training Enhances Auditory Attention Efficiency in Older Adults.
AB  - Auditory cognitive training (ACT) improves attention in older adults; however,
      the underlying neurophysiological mechanisms are still unknown. The present study
      examined the effects of ACT on the P3b event-related potential reflecting
      attention allocation (amplitude) and speed of processing (latency) during
      stimulus categorization and the P1-N1-P2 complex reflecting perceptual processing
      (amplitude and latency). Participants completed an auditory oddball task before
      and after 10 weeks of ACT (n = 9) or a no contact control period (n = 15).
      Parietal P3b amplitudes to oddball stimuli decreased at post-test in the trained
      group as compared to those in the control group, and frontal P3b amplitudes show
      a similar trend, potentially reflecting more efficient attentional allocation
      after ACT. No advantages for the ACT group were evident for auditory perceptual
      processing or speed of processing in this small sample. Our results provide
      preliminary evidence that ACT may enhance the efficiency of attention allocation,
      which may account for the positive impact of ACT on the everyday functioning of
      older adults.

PMID- 29046635
TI  - miRNA in Circulating Microvesicles as Biomarkers for Age-Related Cognitive
      Decline.
AB  - Community dwelling older individuals from the North Florida region were examined
      for health status and a comprehensive neuropsychological battery, including the
      Montreal Cognitive Assessment (MoCA), was performed on each participant. A
      subpopulation (58 females and 39 males) met the criteria for age (60-89) and no
      evidence of mild cognitive impairment, with a MoCA score >=23. Despite the
      stringent criteria for participation, MoCA scores were negatively correlated
      within the limited age range. Extracellular microvesicles were isolated from the
      plasma and samples were found to be positive for the exosome marker CD63, with an
      enrichment of particles within the size range for exosomes. miRNA was extracted
      and examined using next generation sequencing with a stringent criterion (average
      of >=10 counts per million reads) resulting in 117 miRNA for subsequent analysis.
      Characterization of expression confirmed pervious work concerning the relative
      abundance and overall pattern of expression of miRNA in plasma. Correlation
      analysis indicated that most of the miRNAs (74 miRNAs) were positively correlated
      with age (p <0.01). Multiple regression was employed to identify the relationship
      of miRNA expression and MoCA score, accounting for age. MoCA scores were
      negatively correlated with 13 miRNAs. The pattern of expression for cognition
      related miRNA did not match that previously described for Alzheimer's disease.
      Enrichment analysis was employed to identify miRNA-gene interactions to reveal
      possible links to brain function.

PMID- 29046636
TI  - Targeting the Immune System with Plant Lectins to Combat Microbial Infections.
AB  - The arsenal of drugs available to treat infections caused by eukaryotic and
      prokaryotic microbes has been declining exponentially due to antimicrobial
      resistance phenomenon, leading to an urgent need to develop new therapeutic
      strategies. Host-directed immunotherapy has been reported as an attractive option
      to treat microbial infections. It consists in the improvement of host defenses by
      increasing the expression of inflammatory mediators and/or controlling of
      inflammation-induced tissue injury. Although the in vitro antimicrobial and
      immunomodulatory activities of lectins have been extensively demonstrated, few
      studies have evaluated their in vivo effects on experimental models of
      infections. This review aims to highlight the experimental use of
      immunomodulatory plant lectins to improve the host immune response against
      microbial infections. Lectins have been used in vivo both prophylactically and
      therapeutically resulting in the increased survival of mice under microbial
      challenge. Other studies successfully demonstrated that lectins could be used in
      combination with parasite antigens in order to induce a more efficient
      immunization. Therefore, these plant lectins represent new candidates for
      management of microbial infections. Furthermore, immunotherapeutic studies have
      improved our knowledge about the mechanisms involved in host-pathogen
      interactions, and may also help in the discovery of new drug targets.

PMID- 29046637
TI  - Meclizine Prevents Ovariectomy-Induced Bone Loss and Inhibits Osteoclastogenesis
      Partially by Upregulating PXR.
AB  - Pregnane X receptor (PXR) which belongs to the nuclear hormone receptor
      superfamily plays vital roles in several biological functions, especially in the
      inflammatory procedure. Besides that, PXR is revealed by recent studies to have
      essential effects on bone tissue. As an agonist of PXR, meclizine is a piperazine
      derived histamine H1 antagonist, and has been frequently used for prevention and
      treatment of vomiting and nausea. Because osteoclastogenesis is characterized by
      the activation of inflammation-related signaling pathways, we speculated that
      meclizine may affect formation and function of osteoclast. In the present study,
      we explored the effect of meclizine on RANKL-induced osteoclastogenesis both in
      vivo and in vitro. In primary bone marrow-derived macrophages (BMMs), meclizine
      reduced osteoclast formation and bone resorption in a dose-dependent manner,
      while knockdown of PXR with siRNA partially abrogated the osteoclastogenesis
      inhibition of meclizine. On the one hand, at the molecular level, meclizine
      attenuated RANKL-induced activation of c-Fos, NFATc1, nuclear factor-kappaB (NF
      kappaB) and mitogen-activated protein kinase (MAPKs), including ERK and p38, but
      not JNK. Meanwhile, meclizine reduced the expression of osteoclast-specific
      genes, including TRAP, MMP9, Cathepsin K and NFATc1. On the other hand, meclizine
      decreased OVX-induced bone loss by repressing osteoclast activity. In conclusion,
      our results indicated that meclizine inhibits osteoclastogenesis via regulation
      of several RANKL signaling pathways and PXR was involved in the processes.
      Therefore, meclizine may be considered as a novel therapeutic candidate for
      osteoclast-related diseases.

PMID- 29046638
TI  - Blockade of Cannabinoid CB1 Receptors in the Dorsal Periaqueductal Gray Unmasks
      the Antinociceptive Effect of Local Injections of Anandamide in Mice.
AB  - Divergent results in pain management account for the growing number of studies
      aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid
      anandamide (AEA) within several pain-related brain structures. For instance, the
      stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1) and
      Cannabinoid type 1 (CB1) receptors led to paradoxical effects on nociception.
      Here, we attempted to propose a clear and reproducible methodology to achieve the
      antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray
      (dPAG) of mice exposed to the tail-flick test. Accordingly, male Swiss mice
      received intra-dPAG injection of AEA (CB1/TRPV1 agonist), capsaicin (TRPV1
      agonist), WIN (CB1 agonist), AM251 (CB1 antagonist), and 6
      iodonordihydrocapsaicin (6-IODO) (TRPV1 selective antagonist) and their
      nociceptive response was assessed with the tail-flick test. In order to assess
      AEA effects on nociception specifically at vanilloid or cannabinoid (CB)
      substrates into the dPAG, mice underwent an intrinsically inactive dose of AM251
      or 6-IODO followed by local AEA injections and were subjected to the same test.
      While intra-dPAG AEA did not change acute pain, local injections of capsaicin or
      WIN induced a marked TRPV1- and CB1-dependent antinociceptive effect,
      respectively. Regarding the role of AEA specifically at CB/vanilloid substrates,
      while the blockade of TRPV1 did not change the lack of effects of intra-dPAG AEA
      on nociception, local pre-treatment of AM251, a CB1 antagonist, led to a clear
      AEA-induced antinociception. It seems that the exogenous AEA-induced
      antinociception is unmasked when it selectively binds to vanilloid substrates,
      which might be useful to address acute pain in basic and perhaps clinical trials.

PMID- 29046639
TI  - Neonatal Colonic Inflammation Increases Spinal Transmission and Cystathionine
      beta-Synthetase Expression in Spinal Dorsal Horn of Rats with Visceral
      Hypersensitivity.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder
      characterized by chronic abdominal pain and alteration of bowel movements. The
      pathogenesis of visceral hypersensitivity in IBS patients remains largely
      unknown. Hydrogen sulfide (H2S) is reported to play an important role in
      development of visceral hyperalgesia. However, the role of H2S at spinal dorsal
      horn level remains elusive in visceral hypersensitivity. The aim of this study is
      designed to investigate how H2S takes part in visceral hypersensitivity of adult
      rats with neonatal colonic inflammation (NCI). Visceral hypersensitivity was
      induced by neonatal colonic injection of diluted acetic acid. Expression of an
      endogenous H2S synthesizing enzyme cystathionine beta-synthetase (CBS) was
      determined by Western blot. Excitability and synaptic transmission of neurons in
      the substantia gelatinosa (SG) of spinal cord was recorded by patch clamping.
      Here, we showed that expression of CBS in the spinal dorsal horn was
      significantly upregulated in NCI rats. The frequency of glutamatergic synaptic
      activities in SG was markedly enhanced in NCI rats when compared with control
      rats. Application of NaHS increased the frequency of both spontaneous and
      miniature excitatory post-synaptic currents of SG neurons in control rats through
      a presynaptic mechanism. In contrast, application of AOAA, an inhibitor of CBS,
      dramatically suppressed the frequency of glutamatergic synaptic activities of SG
      neurons of NCI rats. Importantly, intrathecal injection of AOAA remarkably
      attenuated visceral hypersensitivity of NCI rats. These results suggest that H2S
      modulates pain signaling likely through a presynaptic mechanism in SG of spinal
      dorsal horn, thus providing a potential therapeutic strategy for treatment for
      chronic visceral pain in patients with IBS.

PMID- 29046640
TI  - Antiparkinsonian Efficacy of Guanosine in Rodent Models of Movement Disorder.
AB  - Guanosine (GUO) is a guanine-based purine nucleoside with important trophic
      functions and promising neuroprotective properties. Although the neuroprotective
      effects of GUO have been corroborated in cellular models of Parkinson's disease
      (PD), its efficacy as an antiparkinsonian agent has not been fully explored in PD
      animal models. Accordingly, we evaluated the effectiveness of GUO in reversing
      motor impairments in several rodent movement disorder models, including
      catalepsy, tremor, and hemiparkinsonism. Our results showed that orally
      administered GUO antagonized reserpine-mediated catalepsy, reduced reserpine
      induced tremulous jaw movements, and potentiated the number of contralateral
      rotations induced by L-3,4-dihydroxyphenylalanine in unilaterally 6
      hydroxidopamine-lesioned rats. In addition, at 5 and 7.5 mg/kg, GUO inhibited L
      DOPA-induced dyskinesia in rats chronically treated with a pro-dopaminergic
      agent. Overall, we describe the therapeutic potential of GUO, which may be
      effective not only for reversing parkinsonian motor impairments but also for
      reducing dyskinesia induced by treatment for PD.

PMID- 29046641
TI  - Buspirone Counteracts MK-801-Induced Schizophrenia-Like Phenotypes through
      Dopamine D3 Receptor Blockade.
AB  - Background: Several efforts have been made to develop effective antipsychotic
      drugs. Currently, available antipsychotics are effective on positive symptoms,
      less on negative symptoms, but not on cognitive impairment, a clinically relevant
      dimension of schizophrenia. Drug repurposing offers great advantages over the
      long-lasting, risky and expensive, de novo drug discovery strategy. To our
      knowledge, the possible antipsychotic properties of buspirone, an azapirone
      anxiolytic drug marketed in 1986 as serotonin 5-HT1A receptor (5-HT1AR) partial
      agonist, have not been extensively investigated despite its intriguing
      pharmacodynamic profile, which includes dopamine D3 (D3R) and D4 receptor (D4R)
      antagonist activity. Multiple lines of evidence point to D3R as a valid
      therapeutic target for the treatment of several neuropsychiatric disorders
      including schizophrenia. In the present study, we tested the hypothesis that
      buspirone, behaving as dopamine D3R antagonist, may have antipsychotic-like
      activity. Materials and Methods: Effects of acute administration of buspirone was
      assessed on a wide-range of schizophrenia-relevant abnormalities induced by a
      single administration of the non-competitive NMDAR antagonist MK-801, in both
      wild-type mice (WT) and D3R-null mutant mice (D3R-/-). Results: Buspirone (3
      mg?kg-1, i.p.) was devoid of cataleptogenic activity in itself, but resulted
      effective in counteracting disruption of prepulse inhibition (PPI),
      hyperlocomotion and deficit of temporal order recognition memory (TOR) induced by
      MK-801 (0.1 mg?kg-1, i.p.) in WT mice. Conversely, in D3R-/- mice, buspirone was
      ineffective in preventing MK-801-induced TOR deficit and it was only partially
      effective in blocking MK-801-stimulated hyperlocomotion. Conclusion: Taken
      together, these results indicate, for the first time, that buspirone, might be a
      potential therapeutic medication for the treatment of schizophrenia. In
      particular, buspirone, through its D3R antagonist activity, may be a useful tool
      for improving the treatment of cognitive deficits in schizophrenia that still
      represents an unmet need of this disease.

PMID- 29046643
TI  - Trigger vs. Substrate: Multi-Dimensional Modulation of QT-Prolongation Associated
      Arrhythmic Dynamics by a hERG Channel Activator.
AB  - Background: Prolongation of the QT interval of the electrocardiogram (ECG),
      underlain by prolongation of the action potential duration (APD) at the cellular
      level, is linked to increased vulnerability to cardiac arrhythmia.
      Pharmacological management of arrhythmia associated with QT prolongation is
      typically achieved through attempting to restore APD to control ranges, reversing
      the enhanced vulnerability to Ca2+-dependent afterdepolarisations (arrhythmia
      triggers) and increased transmural dispersion of repolarisation (arrhythmia
      substrate) associated with APD prolongation. However, such pharmacological
      modulation has been demonstrated to have limited effectiveness. Understanding the
      integrative functional impact of pharmacological modulation requires simultaneous
      investigation of both the trigger and substrate. Methods: We implemented a multi
      scale (cell and tissue) in silico approach using a model of the human ventricular
      action potential, integrated with a model of stochastic 3D spatiotemporal Ca2+
      dynamics, and parameter modification to mimic prolonged QT conditions. We used
      these models to examine the efficacy of the hERG activator MC-II-157c in
      restoring APD to control ranges, examined its effects on arrhythmia triggers and
      substrates, and the interaction of these arrhythmia triggers and substrates.
      Results: QT prolongation conditions promoted the development of spontaneous
      release events underlying afterdepolarisations during rapid pacing. MC-II-157c
      applied to prolonged QT conditions shortened the APD, inhibited the development
      of afterdepolarisations and reduced the probability of afterdepolarisations
      manifesting as triggered activity in single cells. In tissue, QT prolongation
      resulted in an increased transmural dispersion of repolarisation, which
      manifested as an increased vulnerable window for uni-directional conduction
      block. In some cases, MC-II-157c further increased the vulnerable window through
      its effects on INa. The combination of stochastic release event modulation and
      transmural dispersion of repolarisation modulation by MC-II-157c resulted in an
      integrative behavior wherein the arrhythmia trigger is reduced but the arrhythmia
      substrate is increased, leading to variable and non-linear overall vulnerability
      to arrhythmia. Conclusion: The relative balance of reduced trigger and increased
      substrate underlies a multi-dimensional role of MC-II-157c in modulation of
      cardiac arrhythmia vulnerability associated with prolonged QT interval.

PMID- 29046642
TI  - Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure
      Control.
AB  - Oxygen sensing mechanisms are vital for homeostasis and survival. When oxygen
      levels are too low (hypoxia), blood flow has to be increased, metabolism reduced,
      or a combination of both, to counteract tissue damage. These adjustments are
      regulated by local, humoral, or neural reflex mechanisms. The kidney and the
      carotid body are both directly sensitive to falls in the partial pressure of
      oxygen and trigger reflex adjustments and thus act as oxygen sensors. We
      hypothesize a cooperative oxygen sensing function by both the kidney and carotid
      body to ensure maintenance of whole body blood flow and tissue oxygen
      homeostasis. Under pathological conditions of severe or prolonged tissue hypoxia,
      these sensors may become continuously excessively activated and increase
      perfusion pressure chronically. Consequently, persistence of their activity could
      become a driver for the development of hypertension and cardiovascular disease.
      Hypoxia-mediated renal and carotid body afferent signaling triggers unrestrained
      activation of the renin angiotensin-aldosterone system (RAAS). Renal and carotid
      body mediated responses in arterial pressure appear to be synergistic as
      interruption of either afferent source has a summative effect of reducing blood
      pressure in renovascular hypertension. We discuss that this cooperative oxygen
      sensing system can activate/sensitize their own afferent transduction mechanisms
      via interactions between the RAAS, hypoxia inducible factor and erythropoiesis
      pathways. This joint mechanism supports our view point that the development of
      cardiovascular disease involves afferent nerve activation.

PMID- 29046644
TI  - More Relaxation by Deep Breath on Methacholine- Than on Exercise-Induced
      bronchoconstriction during the Routine Testing of Asthmatic Children.
AB  - Deep inspiration (DI) dilates normal airway precontracted with methacholine. The
      fact that this effect is diminished or absent in asthma could be explained by the
      presence of bronchial inflammation. The hypothesis was tested that DI induces
      more relaxation in methacholine induced bronchoconstriction-solely determined by
      the smooth muscle contraction-than in exercise induced bronchoconstriction, which
      is contributed to by both smooth muscle contraction and airway wall inflammation.
      The respiratory conductance (Grs) response to DI was monitored in asthmatic
      children presenting a moderately positive airway response to challenge by
      methacholine (n = 36) or exercise (n = 37), and expressed as the post- to pre-DI
      Grs ratio (GrsDI). Both groups showed similar change in FEV1 after challenge and
      performed a DI of similar amplitude. GrsDI however was significantly larger in
      methacholine than in exercise induced bronchoconstriction (p < 0.02). The
      bronchodilatory effect of DI is thus less during exercise- than methacholine
      induced bronchoconstriction. The observation is consistent with airway wall
      inflammation-that characterizes exercise induced bronchoconstriction-rendering
      the airways less responsive to DI. More generally, it is surmised that less
      relief of bronchoconstriction by DI is to be expected during indirect than direct
      airway challenge. The current suggestion that airway smooth muscle constriction
      and airway wall inflammation may result in opposing effects on the bronchomotor
      action of DI opens important perspective to the routine testing of asthmatic
      children. New crossover research protocols comparing the mechanical consequences
      of the DI maneuver are warranted during direct and indirect bronchial challenges.

PMID- 29046645
TI  - Computational Cardiac Modeling Reveals Mechanisms of Ventricular Arrhythmogenesis
      in Long QT Syndrome Type 8: CACNA1C R858H Mutation Linked to Ventricular
      Fibrillation.
AB  - Functional analysis of the L-type calcium channel has shown that the CACNA1C
      R858H mutation associated with severe QT interval prolongation may lead to
      ventricular fibrillation (VF). This study investigated multiple potential
      mechanisms by which the CACNA1C R858H mutation facilitates and perpetuates VF.
      The Ten Tusscher-Panfilov (TP06) human ventricular cell models incorporating the
      experimental data on the kinetic properties of L-type calcium channels were
      integrated into one-dimensional (1D) fiber, 2D sheet, and 3D ventricular models
      to investigate the pro-arrhythmic effects of CACNA1C mutations by quantifying
      changes in intracellular calcium handling, action potential profiles, action
      potential duration restitution (APDR) curves, dispersion of repolarization (DOR),
      QT interval and spiral wave dynamics. R858H "mutant" L-type calcium current (ICaL
      ) augmented sarcoplasmic reticulum calcium content, leading to the development of
      afterdepolarizations at the single cell level and focal activities at the tissue
      level. It also produced inhomogeneous APD prolongation, causing QT prolongation
      and repolarization dispersion amplification, rendering R858H "mutant" tissue more
      vulnerable to the induction of reentry compared with other conditions. In
      conclusion, altered ICaL due to the CACNA1C R858H mutation increases arrhythmia
      risk due to afterdepolarizations and increased tissue vulnerability to
      unidirectional conduction block. However, the observed reentry is not due to
      afterdepolarizations (not present in our model), but rather to a novel blocking
      mechanism.

PMID- 29046647
TI  - East London Modified-Broset as Decision-Making Tool to Predict Seclusion in
      Psychiatric Intensive Care Units.
AB  - Seclusion is a last resort intervention for management of aggressive behavior in
      psychiatric settings. There is no current objective and practical decision-making
      instrument for seclusion use on psychiatric wards. Our aim was to test the
      predictive and discriminatory characteristics of the East London Modified-Broset
      (ELMB), to delineate its decision-making profile for seclusion of adult
      psychiatric patients, and second to benchmark it against the psychometric
      properties of the Broset Violence Checklist (BVC). ELMB, an 8-item modified
      version of the 6-item BVC, was retrospectively employed to evaluate the seclusion
      decision-making process on two Psychiatric Intensive Care Units (patients n =
      201; incidents n = 2,187). Data analyses were carried out using multivariate
      regression and Receiver Operating Characteristic (ROC) curves. Predictors of
      seclusion were: physical violence toward staff/patients OR = 24.2; non-compliance
      with PRN (pro re nata) medications OR = 9.8; and damage to hospital property OR =
      2.9. ROC analyses indicated that ELMB was significantly more accurate that BVC,
      with higher sensitivity, specificity, and positive likelihood ratio. Results were
      similar across gender. The ELMB is a sensitive and specific instrument that can
      be used to guide the decision-making process when implementing seclusion.

PMID- 29046646
TI  - Role of Sex Hormones in the Control of Vegetative and Metabolic Functions of
      Middle-Aged Women.
AB  - Aims: In women's life, menopause is characterized by significant physiological
      changes often associated with an increase in body mass and obesity-associated
      sicknesses. Numerous researches described interdependencies of estrogen
      deficiency, aging, and resting energy expenditure (REE) downfall in the obesity
      correlated with the menopause. The aim of this study was to determining whether
      healthy, obese menopausal women underwent HRT treatment, showed changes in their
      REE, autonomic asset, and assessment of oxidative stress in comparison with obese
      pre- and post-menopausal women. Methodology: In this study, we measured the body
      composition, the REE, the oxidative stress, the diet assimilation, and the
      autonomic nervous system activity in three groups: pre-menopause women (n = 50),
      post-menopause women following hormone-replacement therapy (HRT; n = 50), and
      post-menopause women not following HRT (n = 50). Results: In the group with HRT a
      significant increase of the sympathetic activity and REE was described. Finally
      this group showed a notable increment of oxidative stress compared with the
      others, and utilizing BIA instrument, the free fat mass was increased respect to
      the fat mass of obese women. Conclusion: The study highlights the importance of
      the HRT-related physiological changes that influence body weight in menopause
      women. This results are important because have a practical implications for
      prevention and/or treatment of the obesity.

PMID- 29046648
TI  - The Relationships among Tryptophan, Kynurenine, Indoleamine 2,3-Dioxygenase,
      Depression, and Neuropsychological Performance.
AB  - It has been suggested that the metabolic enzyme indoleamine 2,3-dioxygenase (IDO)
      is a biological mediator of inflammation related to the psychopathology of
      depression, with a Kynurenine (KYN) increase in the Tryptophan (TRP) metabolic
      pathway, resulting in reduced Serotonin. In this study, we examined KYN, TRP, and
      the ratio of KYN to TRP concentrations * 103 (KT Ratio) in serum and
      cerebrospinal fluid (CSF) in (a) a group of depressed patients and (b) a control
      group of patients referred to a neurologic outpatient clinic for whom no specific
      diagnosis could be established. The KT Ratio is considered an index that
      represents IDO. The participants were examined with the Beck Depression Inventory
      II (BDI-II), the Montgomery Aasberg Depression Rating Scale (MADRS), and a
      neuropsychological test battery. We found no significant differences between the
      two study groups with respect to TRP, KYN, or KT Ratio in serum or CSF.
      Differences in neuropsychological performance between the two patient groups
      could be seen in the following tests: Animal Fluency, Digit Symbol, the DKEFS
      Color-Interference Test (Naming Part), Trail Making Test A and B, and the Grooved
      Pegboard Non-dominant Hand. KYN in serum correlated highly with KYN in CSF. KYN
      in serum correlated significantly with both age and gender. When analyzing males
      and females separately, we found that women had a lower level of TRP in both
      serum (Mann-Whitney U-test: TRP in Serum; p = 0.001) and CSF (Mann-Whitney U
      test: TRP in CSF; p = 0.003). Women had a lower level of KYN in serum (p = 0.029)
      than men did. Age was positively associated with KYN. KYN in CSF correlated only
      with age, however; there were no gender differences. No significant relationship
      was seen between BDI-II and MADRS on the one hand, and KYN and TRP on the other.
      KYN in CSF as the KT Ratio in both serum and CSF was associated with
      neuropsychological performance. Thus, we suggest that KYN and KT Ratio are
      related more strongly to neuropsychological performance than to affective
      symptoms in depression.

PMID- 29046649
TI  - Psychological Flexibility as a Buffer against Caregiver Distress in Families with
      Psychosis.
AB  - Background: Research has shown that caregivers of persons with psychosis play an
      invaluable role in recovery, but unfortunately, often report high levels of
      distress. While cognitive models of caregiver distress have been well-supported,
      there is still limited knowledge of the psychological factors involved. Recent
      advances in cognitive behavioral therapy seem to converge on the importance of
      acceptance- and mindfulness based processes. Aim: To examine the impact of
      psychological flexibility on caregiver distress in the early phases of psychosis,
      while controlling for known predictors of caregiver distress. Method: Within a
      cross-sectional design, 101 caregivers of 38 persons with first-episode psychosis
      in a clinical epidemiological sample completed a series of self-report measures.
      Results: A linear mixed model analysis found that, after controlling for
      caregiver socio-demographic factors, service user symptoms, drug use and global
      functioning, psychological flexibility was a significant predictor of caregiver
      distress. Conclusion: Greater level of psychological flexibility in caregivers,
      seems to be related to lower levels of caregiver distress. This finding
      corresponds to studies within a broad range of emotional disorders. There may be
      important clinical implications in terms of facilitating the process of
      acceptance through interventions from the 'third-wave' or contextual cognitive
      behavioral therapies.

PMID- 29046650
TI  - Alcohol Binge Drinking and Executive Functioning during Adolescent Brain
      Development.
AB  - Alcohol consumption in adolescents causes negative effects on familiar, social,
      academic life, as well as neurocognitive alterations. The binge drinking (BD)
      pattern of alcohol is characterized by the alternation of episodes of heavy
      drinking in a short interval of time, and periods of abstinence, a practice that
      can result in important brain alterations; even more than regular alcohol
      consumption. The prefrontal cortex, which acts as neural support for the
      executive processes, is particularly affected by alcohol; however, not all
      studies are in agreement about how BD alcohol consumption affects executive
      functioning. Some research has found that alcohol consumption in adolescence does
      not significantly affect executive functioning while others found it does. It is
      possible that these discrepancies could be due to the history of alcohol
      consumption, that is, at what age the subjects started drinking. The aim of our
      study is to assess the performance on executive functioning tasks of 13-19-year
      old adolescents according to their pattern of alcohol consumption. We hypothesize
      that BD adolescents will perform worse than non-BD subjects in tasks that
      evaluate executive functions, and these differences will increase depending on
      how long they have been consuming alcohol. Three hundred and twenty-two students
      (48.14% females; age range 13-22 years; mean aged 16.7 +/- 2.59) participated in
      the study; all of them had begun drinking at the age of 13 years. Participant
      were divided into three groups, according to their age range (13-15, 16-18, and
      19-22 years) and divided according to their pattern of alcohol consumption (BD
      and control groups). Then, the subjects were evaluated with neuropsychological
      tasks that assess executive functions like working memory, inhibition, cognitive
      flexibility, or self-control among others. The entire sample showed a normal
      improvement in their executive performance, but this improvement was more stable
      and robust in the control group. Regarding the executive performance among age
      groups, control subjects only obtained better results than BDs in the 19-22-year
      old range, whereas the performance was quite similar at younger ages. Considering
      that all the BD subjects started drinking at the same age (13 years old), it is
      possible that a kind of compensation mechanism exists in the adolescent brain
      which allows them to reach a normal performance in executive tasks. This
      theoretical mechanism would depend upon neuronal labor, which could lose efficacy
      over time with further alcohol ingestion. This process would account for the
      differences in neuropsychological performance, which were only observed in older
      students with a longer history of alcohol consumption.

PMID- 29046652
TI  - How Context Influences Our Perception of Emotional Faces: A Behavioral Study on
      the Kuleshov Effect.
AB  - Facial expressions are of major importance in understanding the mental and
      emotional states of others. So far, most studies on the perception and
      comprehension of emotions have used isolated facial expressions as stimuli; for
      example, photographs of actors displaying facial expressions corresponding to one
      of the so called 'basic emotions.' However, our real experience during social
      interactions is different: facial expressions of emotion are mostly perceived in
      a wider context, constituted by body language, the surrounding environment, and
      our beliefs and expectations. Already in the early twentieth century, the Russian
      filmmaker Lev Kuleshov argued that such context, established by intermediate
      shots of strong emotional content, could significantly change our interpretation
      of facial expressions in film. Prior experiments have shown behavioral effects
      pointing in this direction, but have only used static images as stimuli. Our
      study used a more ecological design with participants watching film sequences of
      neutral faces, crosscut with scenes of strong emotional content (evoking
      happiness or fear, plus neutral stimuli as a baseline condition). The task was to
      rate the emotion displayed by a target person's face in terms of valence,
      arousal, and category. Results clearly demonstrated the presence of a significant
      effect in terms of both valence and arousal in the fear condition only. Moreover,
      participants tended to categorize the target person's neutral facial expression
      choosing the emotion category congruent with the preceding context. Our results
      highlight the context-sensitivity of emotions and the importance of studying them
      under ecologically valid conditions.

PMID- 29046653
TI  - Restorative Qualities of and Preference for Natural and Urban Soundscapes.
AB  - Psychological restoration in urban agglomerations has become a growing challenge.
      Although scientific proof of the significance of nature is irrefutable, an
      increase in built-up areas has led to a decrease in urban greenery. Thus, a
      growing need for restorativeness in urban surroundings has emerged. To
      investigate whether positively evaluated sonic environments, represented by
      natural and urban sounds, have comparable restorative qualities we conducted two
      studies. The aim of the first (Study 1) was to explore the restorative qualities
      of positively assessed natural and urban sounds. Participants (N = 88) were asked
      to listen and to rate 22 recordings (each 1 min long) either from natural or
      urban environments. In the second (Study 2) we investigated whether positively
      evaluated sonic environments (natural and urban), demand for restoration (feeling
      relaxed or fatigued) and company (being alone or with a friend) affect the
      restorative qualities of natural and urban soundscapes. After reading assigned
      scenarios (feeling relaxed or fatigued; being alone or with a friend),
      participants (N = 120) were asked to imagine a walk in presented sonic
      environments and to complete forms (one for each sonic environment) concerning
      the restorative qualities of given soundscapes (natural and urban). Top five
      recordings of natural and urban sonic environments were selected from Study 1 and
      combined into a 154-s soundtrack, to provide a background for the imagined walks
      in both settings. Our findings confirmed that natural sounds are perceived more
      favorably than urban recordings. Even when only the most positively assessed
      soundscapes were compared, nature was still perceived as being more restorative
      than urban areas. Company of a friend was found to be more beneficial in the
      urban surroundings, particularly when there was no need for restoration.

PMID- 29046654
TI  - The Effect of Consistency on Short-Term Memory for Scenes.
AB  - Which is more detectable, the change of a consistent or an inconsistent object in
      a scene? This question has been debated for decades. We noted that the change of
      objects in scenes might simultaneously be accompanied with gist changes. In the
      present study we aimed to examine how the alteration of gist, as well as the
      consistency of the changed objects, modulated change detection. In Experiment 1,
      we manipulated the semantic content by either keeping or changing the consistency
      of the scene. Results showed that the changes of consistent and inconsistent
      scenes were equally detected. More importantly, the changes were more accurately
      detected when scene consistency changed than when the consistency remained
      unchanged, regardless of the consistency of the memory scenes. A phase-scrambled
      version of stimuli was adopted in Experiment 2 to decouple the possible
      confounding effect of low-level factors. The results of Experiment 2 demonstrated
      that the effect found in Experiment 1 was indeed due to the change of high-level
      semantic consistency rather than the change of low-level physical features.
      Together, the study suggests that the change of consistency plays an important
      role in scene short-term memory, which might be attributed to the sensitivity to
      the change of semantic content.

PMID- 29046651
TI  - Robots As Intentional Agents: Using Neuroscientific Methods to Make Robots Appear
      More Social.
AB  - Robots are increasingly envisaged as our future cohabitants. However, while
      considerable progress has been made in recent years in terms of their
      technological realization, the ability of robots to interact with humans in an
      intuitive and social way is still quite limited. An important challenge for
      social robotics is to determine how to design robots that can perceive the user's
      needs, feelings, and intentions, and adapt to users over a broad range of
      cognitive abilities. It is conceivable that if robots were able to adequately
      demonstrate these skills, humans would eventually accept them as social
      companions. We argue that the best way to achieve this is using a systematic
      experimental approach based on behavioral and physiological neuroscience methods
      such as motion/eye-tracking, electroencephalography, or functional near-infrared
      spectroscopy embedded in interactive human-robot paradigms. This approach
      requires understanding how humans interact with each other, how they perform
      tasks together and how they develop feelings of social connection over time, and
      using these insights to formulate design principles that make social robots
      attuned to the workings of the human brain. In this review, we put forward the
      argument that the likelihood of artificial agents being perceived as social
      companions can be increased by designing them in a way that they are perceived as
      intentional agents that activate areas in the human brain involved in social
      cognitive processing. We first review literature related to social-cognitive
      processes and mechanisms involved in human-human interactions, and highlight the
      importance of perceiving others as intentional agents to activate these social
      brain areas. We then discuss how attribution of intentionality can positively
      affect human-robot interaction by (a) fostering feelings of social connection,
      empathy and prosociality, and by (b) enhancing performance on joint human-robot
      tasks. Lastly, we describe circumstances under which attribution of
      intentionality to robot agents might be disadvantageous, and discuss challenges
      associated with designing social robots that are inspired by neuroscientific
      principles.

PMID- 29046655
TI  - Change Blindness Is Influenced by Both Contrast Energy and Subjective Importance
      within Local Regions of the Image.
AB  - Our visual system receives an enormous amount of information, but not all
      information is retained. This is exemplified by the fact that subjects fail to
      detect large changes in a visual scene, i.e., change-blindness. Current theories
      propose that our ability to detect these changes is influenced by the gist or
      interpretation of an image. On the other hand, stimulus-driven image features
      such as contrast energy dominate the representation in early visual cortex (De
      Valois and De Valois, 1988; Boynton et al., 1999; Olman et al., 2004; Mante and
      Carandini, 2005; Dumoulin et al., 2008). Here we investigated whether contrast
      energy contributes to our ability to detect changes within a visual scene. We
      compared the ability to detect changes in contrast energy together with changes
      to a measure of the interpretation of an image. We used subjective important
      aspects of the image as a measure of the interpretation of an image. We measured
      reaction times while manipulating the contrast energy and subjective important
      properties using the change blindness paradigm. Our results suggest that our
      ability to detect changes in a visual scene is not only influenced by the
      subjective importance, but also by contrast energy. Also, we find that contrast
      energy and subjective importance interact. We speculate that contrast energy and
      subjective important properties are not independently represented in the visual
      system. Thus, our results suggest that the information that is retained of a
      visual scene is both influenced by stimulus-driven information as well as the
      interpretation of a scene.

PMID- 29046656
TI  - Blood Alcohol Concentration-Related Lower Performance in Immediate Visual Memory
      and Working Memory in Adolescent Binge Drinkers.
AB  - The binge drinking (BD) pattern of alcohol consumption is prevalent during
      adolescence, a period characterized by critical changes to the structural and
      functional development of brain areas related with memory and cognition. There is
      considerable evidence of the cognitive dysfunctions caused by the neurotoxic
      effects of BD in the not-yet-adult brain. Thus, the aim of the present study was
      to evaluate the effects of different blood alcohol concentrations (BAC) on memory
      during late adolescence (18-19 years old) in males and females with a history of
      BD. The sample consisted of 154 adolescents (67 males and 87 females) that were
      classified as refrainers if they had never previously drunk alcoholic drinks and
      as binge drinkers if they had drunk six or more standard drink units in a row for
      men or five or more for women at a minimum frequency of three occasions in a
      month, throughout the previous 12 months. After intake of a high acute dose of
      alcohol by binge drinkers or a control refreshment by refrainers and binge
      drinkers, subjects were distributed into four groups for each gender according to
      their BAC: BAC0-R (0 g/L, in refrainers), BAC0-BD (0 g/L, in binge drinkers),
      BAC1 (0.3 - 0.5 g/L, in binge drinkers) or BAC2 (0.54 - 1.1 g/L, in binge
      drinkers). The subjects' immediate visual memory and working memory were then
      measured according to the Wechsler Memory Scale (WMS-III). The BAC1 group showed
      lower scores of immediate visual memory but not of working memory, while lower
      performance in both memories were found in the BAC2 group. Therefore, the brain
      of binge drinkers with moderate BAC could be employing compensatory mechanisms
      from additional brain areas to perform a working memory task adequately, but
      these resources would be undermined when BAC is higher (>0.5 g/L). No gender
      differences were found in BAC-related lower performance in immediate visual
      memory and working memory. In conclusion, immediate visual memory is more
      sensitive than working memory to the neurotoxic effects of alcohol in adolescent
      binge drinkers of both genders, being a BAC-related lower performance, and
      without obvious differences between males and females.

PMID- 29046657
TI  - The Palliative Function of Hostile Sexism among High and Low-Status Chilean
      Students.
AB  - Previous studies have demonstrated that justifying the social, economic, and
      political systems is associated with psychological well-being, which has been
      termed as the palliative function of ideology. However, little research has been
      conducted on gender stereotypes among children, comparing by socioeconomic
      status. This study aimed to fill this gap in the system justification literature.
      We present data from the Chilean version of the International Survey of Children
      Well-Being (ISCWeB), which was conducted in 2012. We found that the palliative
      function of gender stereotypes is present among this sample, being qualified by a
      socioeconomic status by hostile gender stereotype interaction. In other words,
      the effect on the psychological well-being was observed in low-status, but not in
      high-status students. These results extend the previous knowledge about the
      palliative function of the ideology, suggesting why the low-status members of a
      society actively engage in system justification.

PMID- 29046658
TI  - Dissociated Spatial-Arithmetic Associations in Horizontal and Vertical
      Dimensions.
AB  - Spatial-numerical associations (small numbers-left/lower space and large numbers
      right/upper space) are regularly found in elementary number processing. Recently,
      the interest in this phenomenon has been extended from elementary number
      processing to mental arithmetic. Many studies have demonstrated horizontal
      spatial-arithmetic associations, i.e., solving addition or subtraction problems
      cause spatial shifts of attention rightward or leftward, respectively. However,
      the role of this effect in the vertical dimension has not been addressed. This is
      problematic because it leaves the analogy between elementary number processing
      and arithmetic incomplete. In order to make a strong case for a similarity
      between elementary number processing and mental arithmetic, a spatial-arithmetic
      association should be observed in the vertical dimension too. Here, we adopted
      the target detection paradigm from Liu et al. (2017) to replicate the horizontal
      spatial-arithmetic association, and meanwhile investigate whether this effect
      also exists in the vertical direction. Our results confirmed that addition could
      induce covert movement to right side and subtraction to left side. However, such
      a spatial-arithmetic association was not found in the vertical dimension. The
      implication of these findings is discussed.

PMID- 29046659
TI  - Four Distinctions for the Auditory "Wastebasket" of Timbre.

PMID- 29046660
TI  - Beyond Clinical Case Studies in Psychoanalysis: A Review of Psychoanalytic
      Empirical Single Case Studies Published in ISI-Ranked Journals.
AB  - Single case studies are at the origin of both theory development and research in
      the field of psychoanalysis and psychotherapy. While clinical case studies are
      the hallmark of psychoanalytic theory and practice, their scientific value has
      been strongly criticized. To address problems with the subjective bias of
      retrospective therapist reports and uncontrollability of clinical case studies,
      systematic approaches to investigate psychotherapy process and outcome at the
      level of the single case have been developed. Such empirical case studies are
      also able to bridge the famous gap between academic research and clinical
      practice as they provide clinically relevant insights into how psychotherapy
      works. This study presents a review of psychoanalytic empirical case studies
      published in ISI-ranked journals and maps the characteristics of the study,
      therapist, patient en therapies that are investigated. Empirical case studies
      increased in quantity and quality (amount of information and systematization)
      over time. While future studies could pay more attention to providing contextual
      information on therapist characteristics and informed consent considerations, the
      available literature provides a basis to conduct meta-studies of single cases and
      as such contribute to knowledge aggregation.

PMID- 29046661
TI  - Mitophagy in Parkinson's Disease: Pathogenic and Therapeutic Implications.
AB  - Neurons affected in Parkinson's disease (PD) experience mitochondrial dysfunction
      and bioenergetic deficits that occur early and promote the disease-related alpha
      synucleinopathy. Emerging findings suggest that the autophagy-lysosome pathway,
      which removes damaged mitochondria (mitophagy), is also compromised in PD and
      results in the accumulation of dysfunctional mitochondria. Studies using genetic
      modulated or toxin-induced animal and cellular models as well as postmortem human
      tissue indicate that impaired mitophagy might be a critical factor in the
      pathogenesis of synaptic dysfunction and the aggregation of misfolded proteins,
      which in turn impairs mitochondrial homeostasis. Interventions that stimulate
      mitophagy to maintain mitochondrial health might, therefore, be used as an
      approach to delay the neurodegenerative processes in PD.

PMID- 29046662
TI  - Shared Medical Appointments May Be Effective for Improving Clinical and
      Behavioral Outcomes in Type 2 Diabetes: A Narrative Review.
AB  - Type 2 diabetes mellitus (T2DM) is a complex chronic disease affecting over 400
      million people worldwide. Managing T2DM and its associated complications in
      individual patient consultations poses substantial challenges to physicians due
      to limited time and resources and lack of access to multidisciplinary teams.
      Shared medical appointments (SMAs) are consecutive medical consultations provided
      by a physician in a group setting, where integrated medical care and patient
      education are delivered in a single session. SMAs allow physicians to deliver the
      same level of care to multiple patients at the same time, thereby maximizing
      available resources. However, the effectiveness and practicality of SMAs in the
      management of T2DM remains unknown. This narrative review summarizes current and
      emerging evidence regarding the effectiveness of SMAs in improving clinical
      outcomes in patients with T2DM, as well as whether SMAs are associated with
      reduced costs and improved diabetes-related behavioral and lifestyle changes. An
      extensive literature search was conducted on major electronic databases including
      PubMed and Google Scholar using keywords, including SMAs, group visits, and T2DM
      to identify all studies of SMAs in patients with T2DM. Studies in type 1 diabetes
      or mixed or unspecified populations were excluded, as well as studies where SMAs
      did not involve a physician since these do not meet the classical definition of a
      SMA. Nineteen studies were identified and are included in this review. Overall,
      current evidence suggests that SMAs delivered regularly over time may be
      effective in improving glycemic outcomes, diabetes knowledge, and some diabetes
      related behaviors. However, the main limitation of existing studies was the
      paucity of comparisons with standard care which limits the ability to draw
      conclusions regarding whether SMAs are superior to standard care in T2DM
      management. Moreover, the small number of studies and substantial heterogeneity
      in study designs, populations, and interventions creates difficulties in
      establishing the practicality and efficiency of SMAs in the clinical care
      setting. We conclude that there remains a need for larger studies to identify
      populations who may or may not benefit from the SMA model of care and to clarify
      the potential benefits and barriers to implementing SMAs into routine diabetes
      care.

PMID- 29046663
TI  - Reclassification of Paenibacillus riograndensis as a Genomovar of Paenibacillus
      sonchi: Genome-Based Metrics Improve Bacterial Taxonomic Classification.
AB  - Species from the genus Paenibacillus are widely studied due to their
      biotechnological relevance. Dozens of novel species descriptions of this genus
      were published in the last couple of years, but few utilized genomic data as
      classification criteria. Here, we demonstrate the importance of using genome
      based metrics and phylogenetic analyses to identify and classify Paenibacillus
      strains. For this purpose, Paenibacillus riograndensis SBR5T, Paenibacillus
      sonchi X19-5T, and their close relatives were compared through phenotypic,
      genotypic, and genomic approaches. With respect to P. sonchi X19-5T, P.
      riograndensis SBR5T, Paenibacillus sp. CAR114, and Paenibacillus sp. CAS34
      presented ANI (average nucleotide identity) values ranging from 95.61 to 96.32%,
      gANI (whole-genome average nucleotide identity) values ranging from 96.78 to
      97.31%, and dDDH (digital DNA-DNA hybridization) values ranging from 68.2 to
      73.2%. Phylogenetic analyses of 16S rRNA, gyrB, recA, recN, and rpoB genes and
      concatenated proteins supported the monophyletic origin of these Paenibacillus
      strains. Therefore, we propose to assign Paenibacillus sp. CAR114 and
      Paenibacillus sp. CAS34 to P. sonchi species, and reclassify P. riograndensis
      SBR5T as a later heterotypic synonym of P. sonchi (type strain X19-5T), with the
      creation of three novel genomovars, P. sonchi genomovar Sonchi (type strain X19
      5T), P. sonchi genomovar Riograndensis (type strain SBR5T), P. sonchi genomovar
      Oryzarum (type strain CAS34T = DSM 102041T; = BR10511T).

PMID- 29046664
TI  - Regulation-Structured Dynamic Metabolic Model Provides a Potential Mechanism for
      Delayed Enzyme Response in Denitrification Process.
AB  - In a recent study of denitrification dynamics in hyporheic zone sediments, we
      observed a significant time lag (up to several days) in enzymatic response to the
      changes in substrate concentration. To explore an underlying mechanism and
      understand the interactive dynamics between enzymes and nutrients, we developed a
      trait-based model that associates a community's traits with functional enzymes,
      instead of typically used species guilds (or functional guilds). This enzyme
      based formulation allows to collectively describe biogeochemical functions of
      microbial communities without directly parameterizing the dynamics of species
      guilds, therefore being scalable to complex communities. As a key component of
      modeling, we accounted for microbial regulation occurring through transcriptional
      and translational processes, the dynamics of which was parameterized based on the
      temporal profiles of enzyme concentrations measured using a new signature peptide
      based method. The simulation results using the resulting model showed several
      days of a time lag in enzymatic responses as observed in experiments. Further,
      the model showed that the delayed enzymatic reactions could be primarily
      controlled by transcriptional responses and that the dynamics of transcripts and
      enzymes are closely correlated. The developed model can serve as a useful tool
      for predicting biogeochemical processes in natural environments, either
      independently or through integration with hydrologic flow simulators.

PMID- 29046665
TI  - Boeravinone B, A Novel Dual Inhibitor of NorA Bacterial Efflux Pump of
      Staphylococcus aureus and Human P-Glycoprotein, Reduces the Biofilm Formation and
      Intracellular Invasion of Bacteria.
AB  - This study elucidated the role of boeravinone B, a NorA multidrug efflux pump
      inhibitor, in biofilm inhibition. The effects of boeravinone B plus
      ciprofloxacin, a NorA substrate, were evaluated in NorA-overexpressing, wild
      type, and knocked-out Staphylococcus aureus (SA-1199B, SA-1199, and SA-K1758,
      respectively). The mechanism of action was confirmed using the ethidium bromide
      accumulation and efflux assay. The role of boeravinone B as a human P
      glycoprotein (P-gp) inhibitor was examined in the LS-180 (colon cancer) cell
      line. Moreover, its role in the inhibition of biofilm formation and intracellular
      invasion of S. aureus in macrophages was studied. Boeravinone B reduced the
      minimum inhibitory concentration (MIC) of ciprofloxacin against S. aureus and its
      methicillin-resistant strains; the effect was stronger in SA-1199B. Furthermore,
      time-kill kinetics revealed that boeravinone B plus ciprofloxacin, at
      subinhibitory concentration (0.25 * MIC), is as equipotent as that at the MIC
      level. This combination also had a reduced mutation prevention concentration.
      Boeravinone B reduced the efflux of ethidium bromide and increased the
      accumulation, thus strengthening the role as a NorA inhibitor. Biofilm formation
      was reduced by four-eightfold of the minimal biofilm inhibitory concentration of
      ciprofloxacin, effectively preventing bacterial entry into macrophages.
      Boeravinone B effectively inhibited P-gp with half maximal inhibitory
      concentration (IC50) of 64.85 MUM. The study concluded that boeravinone B not
      only inhibits the NorA-mediated efflux of fluoroquinolones but also considerably
      inhibits the biofilm formation of S. aureus. Its P-gp inhibition activity
      demonstrates its potential as a bioavailability and bioefficacy enhancer.

PMID- 29046666
TI  - Molecular Serotype-Specific Identification of Non-type b Haemophilus influenzae
      by Loop-Mediated Isothermal Amplification.
AB  - Over the past four decades, the incidence of meningitis caused by Haemophilus
      influenzae in children has decreased due to widespread vaccination against H.
      influenzae type b (Hib). The incidence of invasive diseases due to H. influenzae
      types not included in the vaccines, however, has increased. At present, there are
      a limited number of diagnostics available to detect non-type b H. influenzae. To
      address this issue, we developed a rapid, simple, and cost-effective method for
      detecting serotypes of H. influenzae. We designed LAMP primer sets based on
      published sequences for H. influenzae capsular types a, c, d, e, and f. The assay
      was evaluated to determine test reactivity, specificity, and sensitivity. To
      support its use in patients with suspected meningitis, we evaluated the detection
      limit of the non-Hib serotype specific LAMP assay using bacterial genomic DNA
      spiked cerebrospinal fluid (CSF) specimens. The reactivity and specificity of the
      LAMP assays were confirmed using six serotypes and non-typeable H. influenzae
      strains, plus eight strains of other Haemophilus species and non-Haemophilus
      genera. The detection limits of the LAMP assay for capsular types a, c, d, e, and
      f were 102, 102, 102, 103, and 10 copies per reaction, while those of the PCR
      assay were 104, 104, 103, 103, and 104 genome copies per reaction, respectively.
      Using DNA-spiked CSF specimens, the detection limit of the LAMP assay was
      equivalent to that using purified DNA as the template. However, the detection
      limit of the PCR was reduced from 103 to 104 genome copies per reaction for
      serotype d and from 103 to 105 genome copies per reaction for serotype e. To the
      best of our knowledge, this is the first report of a serotype-specific
      identification assay for H. influenzae using the LAMP method. Our results suggest
      the potential of LAMP methods for patients with suspected meningitis in resource
      limited laboratories or public health surveillance systems.

PMID- 29046667
TI  - Nanopore Long-Read Guided Complete Genome Assembly of Hydrogenophaga intermedia,
      and Genomic Insights into 4-Aminobenzenesulfonate, p-Aminobenzoic Acid and
      Hydrogen Metabolism in the Genus Hydrogenophaga.
AB  - We improved upon the previously reported draft genome of Hydrogenophaga
      intermedia strain PBC, a 4-aminobenzenesulfonate-degrading bacterium, by
      supplementing the assembly with Nanopore long reads which enabled the
      reconstruction of the genome as a single contig. From the complete genome, major
      genes responsible for the catabolism of 4-aminobenzenesulfonate in strain PBC are
      clustered in two distinct genomic regions. Although the catabolic genes for 4
      sulfocatechol, the deaminated product of 4-aminobenzenesulfonate, are only found
      in H. intermedia, the sad operon responsible for the first deamination step of 4
      aminobenzenesulfonate is conserved in various Hydrogenophaga strains. The absence
      of pabB gene in the complete genome of H. intermedia PBC is consistent with its p
      aminobenzoic acid (pABA) auxotrophy but surprisingly comparative genomics
      analysis of 14 Hydrogenophaga genomes indicate that pABA auxotrophy is not an
      uncommon feature among members of this genus. Of even more interest, several
      Hydrogenophaga strains do not possess the genomic potential for hydrogen
      oxidation, calling for a revision to the taxonomic description of Hydrogenophaga
      as "hydrogen eating bacteria."

PMID- 29046668
TI  - Characterization of Anti-bacterial Compounds from the Seed Coat of Chinese
      Windmill Palm Tree (Trachycarpus fortunei).
AB  - The increasing of multidrug resistance in bacterial associated infections has
      impaired the current antimicrobial therapy and it forces the search for other
      alternatives. In this study, we aimed to find the in vitro antibacterial activity
      of seed coat of Trachycarpus fortunei against a panel of clinically important
      bacterial species. Ethanolic extracts of target tissues were fractionated through
      macro porous resin by column chromatography, using ethanol as an organic solvent
      with a concentration gradient of 0-100%, each along with 20% concentration
      increment. The minimum inhibitory (MIC) concentrations of all fractions were
      measured. It is found that 20% ethanolic fraction showed the most significant
      inhibition against tested bacterial species. All fractions were analyzed by Ultra
      Performance Liquid Chromatography/mass spectrometry (UPLC/MS) and compounds were
      identified by comparing mass spectra with standard libraries. By pairing the
      identified compounds from different fractions with the antibacterial activity of
      each fraction, it was shown that compounds stearamide (7), 1-(4-Fluorophenyl)-2
      (methylthio)-1H-imidazole-5-carboxylic acid (9) and 2,4,5 triacetoxybiphenyl (10)
      topped in the list for anti-bacterial activity. Further experiment with pure
      chemicals verified that compounds 9 and 10 have antibacterial activity against
      Gram-negative bacteria. Whereas, the lowest MIC value (39.06 MUg/mL) was obtained
      by compound 10 against Staphylococcus epidermidis. Hence, the seed coat of T.
      fortunei with its antimicrobial spectrum could be a good candidate for further
      bactericidal research.

PMID- 29046669
TI  - Susceptibility to Mycobacterium ulcerans Disease (Buruli ulcer) Is Associated
      with IFNG and iNOS Gene Polymorphisms.
AB  - Buruli ulcer (BU) is a chronic necrotizing disease of the skin and subcutaneous
      fat tissue. The causative agent, Mycobacterium ulcerans, produces mycolactone, a
      macrolide toxin, which causes apoptosis of mammalian cells. Only a small
      proportion of individuals exposed to M. ulcerans develop clinical disease, as
      surrounding macrophages may control the infection by bacterial killing at an
      early stage, while mycolactone concentration is still low. Otherwise, bacterial
      multiplication leads to in higher concentrations of mycolactone, with formation
      of necrotizing lesions that are no more accessible to immune cells. By typing a
      cohort of 96 Ghanaian BU patients and 384 endemic controls without BU, we show an
      association between BU and single nucleotide polymorphisms (SNPs) in iNOS
      (rs9282799) and IFNG (rs2069705). Both polymorphisms influence promoter activity
      in vitro. A previously reported SNP in SLC11A1 (NRAMP, rs17235409) tended to be
      associated with BU. Altogether, these data reflect the importance of IFNG
      signaling in early defense against M. ulcerans infection.

PMID- 29046670
TI  - Analytical Performance of Four Polymerase Chain Reaction (PCR) and Real Time PCR
      (qPCR) Assays for the Detection of Six Leishmania Species DNA in Colombia.
AB  - Leishmaniasis comprises a spectrum of parasitic diseases caused by protozoans of
      the genus Leishmania. Molecular tools have been widely employed for the detection
      of Leishmania due to its high sensitivity and specificity. However, the
      analytical performance of molecular platforms as PCR and real time PCR (qPCR)
      including a wide variety of molecular markers has never been evaluated. Herein,
      the aim was to evaluate the analytical performance of 4 PCR-based assays
      (designed on four different targets) and applied on conventional and real-time
      PCR platforms. We evaluated the analytical performance of conventional PCR and
      real time PCR, determining exclusivity and inclusivity, Anticipated Reportable
      Range (ARR), limit of detection (LoD) and accuracy using primers directed to
      kDNA, HSP70, 18S and ITS-1 targets. We observed that the kDNA was the most
      sensitive but does not meet the criterion of exclusivity. The HSP70 presented a
      higher LoD in conventional PCR and qPCR in comparison with the other markers (1 *
      101 and 1 * 10-1 equivalent parasites/mL respectively) and had a higher
      coefficient of variation in qPCR. No statistically significant differences were
      found between the days of the test with the four molecular markers. The present
      study revealed that the 18S marker presented the best performance in terms of
      analytical sensitivity and specificity for the qPCR in the species tested
      (species circulating in Colombia). Therefore, we recommend to explore the
      analytical and diagnostic performance in future studies using a broader number of
      species across America.

PMID- 29046672
TI  - Cross-Resistance of UV- or Chlorine Dioxide-Resistant Echovirus 11 to Other
      Disinfectants.
AB  - The emergence of waterborne viruses with resistance to disinfection has been
      demonstrated in the laboratory and in the environment. Yet, the implications of
      such resistance for virus control remain obscure. In this study we investigate if
      viruses with resistance to a given disinfection method exhibit cross-resistance
      to other disinfectants. Chlorine dioxide (ClO2)- or UV-resistant populations of
      echovirus 11 were exposed to five inactivating treatments (free chlorine, ClO2,
      UV radiation, sunlight, and heat), and the extent of cross-resistance was
      determined. The ClO2-resistant population exhibited cross-resistance to free
      chlorine, but to none of the other inactivating treatments tested. We furthermore
      demonstrated that ClO2 and free chlorine act by a similar mechanism, in that they
      mainly inhibit the binding of echovirus 11 to its host cell. As such, viruses
      with host binding mechanisms that can withstand ClO2 treatment were also better
      able to withstand oxidation by free chlorine. Conversely, the UV-resistant
      population was not significantly cross-resistant to any other disinfection
      treatment. Overall, our results indicate that viruses with resistance to multiple
      disinfectants exist, but that they can be controlled by inactivating methods that
      operate by a distinctly different mechanism. We therefore suggest to utilize two
      disinfection barriers that act by different mechanisms in order to control
      disinfection-resistant viruses.

PMID- 29046671
TI  - Generation of Persister Cells of Pseudomonas aeruginosa and Staphylococcus aureus
      by Chemical Treatment and Evaluation of Their Susceptibility to Membrane
      Targeting Agents.
AB  - Persister cells (PCs) are a subset of dormant, phenotypic variants of regular
      bacteria, highly tolerant to antibiotics. Generation of PCs in vivo may account
      for the recalcitrance of most chronic infections to antimicrobial treatment and
      demands for the identification of new antimicrobial agents able to target such
      cells. The present study explored the possibility to obtain in vitro PCs of
      Pseudomonas aeruginosa and Staphylococcus aureus at high efficiency through
      chemical treatment, and to test their susceptibility to structurally different
      antimicrobial peptides (AMPs) and two clinically used peptide-based antibiotics,
      colistin and daptomycin. The main mechanism of action of these molecules (i.e.,
      membrane-perturbing activity) renders them potential candidates to act against
      dormant cells. Exposure of stationary-phase cultures to optimized concentrations
      of the uncoupling agent cyanide m-chlorophenylhydrazone (CCCP) was able to
      generate at high efficiency PCs exhibiting an antibiotic-tolerant phenotype
      toward different classes of antibiotics. The metabolic profile of CCCP-treated
      bacteria was investigated by monitoring bacterial heat production through
      isothermal microcalorimetry and by evaluating oxidoreductase activity by flow
      cytometry. CCCP-pretreated bacteria of both bacterial species underwent a
      substantial decrease in heat production and oxidoreductase activity, as compared
      to the untreated controls. After CCCP removal, induced persisters showed a delay
      in heat production that correlated with a lag phase before resumption of normal
      growth. The metabolic reactivation of bacteria coincided with their reversion to
      an antibiotic-sensitive phenotype. Interestingly, PCs generated by CCCP treatment
      resulted highly sensitive to three different membrane-targeting AMPs at levels
      comparable to those of CCCP-untreated bacteria. Colistin was also highly active
      against PCs of P. aeruginosa, while daptomycin killed PCs of S. aureus only at
      concentrations 32 to 64-fold higher than those of the tested AMPs. In conclusion,
      CCCP treatment was demonstrated to be a suitable method to generate in vitro PCs
      of medically important bacterial species at high efficiency. Importantly, unlike
      conventional antibiotics, structurally different AMPs were able to eradicate PCs
      suggesting that such molecules might represent valid templates for the
      development of new antimicrobials active against persisters.

PMID- 29046673
TI  - Genome of Ca. Pandoraea novymonadis, an Endosymbiotic Bacterium of the
      Trypanosomatid Novymonas esmeraldas.
AB  - We have sequenced, annotated, and analyzed the genome of Ca. Pandoraea
      novymonadis, a recently described bacterial endosymbiont of the trypanosomatid
      Novymonas esmeraldas. When compared with genomes of its free-living relatives, it
      has all the hallmarks of the endosymbionts' genomes, such as significantly
      reduced size, extensive gene loss, low GC content, numerous gene rearrangements,
      and low codon usage bias. In addition, Ca. P. novymonadis lacks mobile elements,
      has a strikingly low number of pseudogenes, and almost all genes are single
      copied. This suggests that it already passed the intensive period of host
      adaptation, which still can be observed in the genome of Polynucleobacter
      necessarius, a certainly recent endosymbiont. Phylogenetically, Ca. P.
      novymonadis is more related to P. necessarius, an intracytoplasmic bacterium of
      free-living ciliates, than to Ca. Kinetoplastibacterium spp., the only other
      known endosymbionts of trypanosomatid flagellates. As judged by the extent of the
      overall genome reduction and the loss of particular metabolic abilities
      correlating with the increasing dependence of the symbiont on its host, Ca. P.
      novymonadis occupies an intermediate position P. necessarius and Ca.
      Kinetoplastibacterium spp. We conclude that the relationships between Ca. P.
      novymonadis and N. esmeraldas are well-established, although not as fine-tuned as
      in the case of Strigomonadinae and their endosymbionts.

PMID- 29046675
TI  - Interpreting T-Cell Cross-reactivity through Structure: Implications for TCR
      Based Cancer Immunotherapy.
AB  - Immunotherapy has become one of the most promising avenues for cancer treatment,
      making use of the patient's own immune system to eliminate cancer cells. Clinical
      trials with T-cell-based immunotherapies have shown dramatic tumor regressions,
      being effective in multiple cancer types and for many different patients.
      Unfortunately, this progress was tempered by reports of serious (even fatal) side
      effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an
      essential part of the adaptive immune system. Cytotoxic T-cells are regularly
      involved in surveillance and are capable of both eliminating diseased cells and
      generating protective immunological memory. The specificity of a given T-cell is
      determined through the structural interaction between the T-cell receptor (TCR)
      and a peptide-loaded major histocompatibility complex (MHC); i.e., an
      intracellular peptide-ligand displayed at the cell surface by an MHC molecule.
      However, a given TCR can recognize different peptide-MHC (pMHC) complexes, which
      can sometimes trigger an unwanted response that is referred to as T-cell cross
      reactivity. This has become a major safety issue in TCR-based immunotherapies,
      following reports of melanoma-specific T-cells causing cytotoxic damage to
      healthy tissues (e.g., heart and nervous system). T-cell cross-reactivity has
      been extensively studied in the context of viral immunology and tissue
      transplantation. Growing evidence suggests that it is largely driven by
      structural similarities of seemingly unrelated pMHC complexes. Here, we review
      recent reports about the existence of pMHC "hot-spots" for cross-reactivity and
      propose the existence of a TCR interaction profile (i.e., a refinement of a more
      general TCR footprint in which some amino acid residues are more important than
      others in triggering T-cell cross-reactivity). We also make use of available
      structural data and pMHC models to interpret previously reported cross-reactivity
      patterns among virus-derived peptides. Our study provides further evidence that
      structural analyses of pMHC complexes can be used to assess the intrinsic
      likelihood of cross-reactivity among peptide-targets. Furthermore, we hypothesize
      that some apparent inconsistencies in reported cross-reactivities, such as a
      preferential directionality, might also be driven by particular structural
      features of the targeted pMHC complex. Finally, we explain why TCR-based
      immunotherapy provides a special context in which meaningful T-cell cross
      reactivity predictions can be made.

PMID- 29046674
TI  - TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical
      Development.
AB  - TBVAC2020 is a research project supported by the Horizon 2020 program of the
      European Commission (EC). It aims at the discovery and development of novel
      tuberculosis (TB) vaccines from preclinical research projects to early clinical
      assessment. The project builds on previous collaborations from 1998 onwards
      funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in
      attracting new partners from outstanding laboratories from all over the world,
      now totaling 40 institutions. Next to the development of novel vaccines, TB
      biomarker development is also considered an important asset to facilitate
      rational vaccine selection and development. In addition, TBVAC2020 offers
      portfolio management that provides selection criteria for entry, gating, and
      priority settings of novel vaccines at an early developmental stage. The
      TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data
      sharing between partners with the common aim of working toward the development of
      an effective TB vaccine. Close links with funders and other consortia with shared
      interests further contribute to this goal.

PMID- 29046676
TI  - Therapeutic Antibodies: What Have We Learnt from Targeting CD20 and Where Are We
      Going?
AB  - Therapeutic monoclonal antibodies (mAbs) have become one of the fastest growing
      classes of drugs in recent years and are approved for the treatment of a wide
      range of indications, from cancer to autoimmune disease. Perhaps the best studied
      target is the pan B-cell marker CD20. Indeed, the first mAb to receive approval
      by the Food and Drug Administration for use in cancer treatment was the CD20
      targeting mAb rituximab (Rituxan(r)). Since its approval for relapsed/refractory
      non-Hodgkin's lymphoma in 1997, rituximab has been licensed for use in the
      treatment of numerous other B-cell malignancies, as well as autoimmune
      conditions, including rheumatoid arthritis. Despite having a significant impact
      on the treatment of these patients, the exact mechanisms of action of rituximab
      remain incompletely understood. Nevertheless, numerous second- and third
      generation anti-CD20 mAbs have since been developed using various strategies to
      enhance specific effector functions thought to be key for efficacy. A plethora of
      knowledge has been gained during the development and testing of these mAbs, and
      this knowledge can now be applied to the design of novel mAbs directed to targets
      beyond CD20. As we enter the "post-rituximab" era, this review will focus on the
      lessons learned thus far through investigation of anti-CD20 mAb. Also discussed
      are current and future developments relating to enhanced effector function, such
      as the ability to form multimers on the target cell surface. These strategies
      have potential applications not only in oncology but also in the improved
      treatment of autoimmune disorders and infectious diseases. Finally, potential
      approaches to overcoming mechanisms of resistance to anti-CD20 therapy are
      discussed, chiefly involving the combination of anti-CD20 mAbs with various other
      agents to resensitize patients to treatment.

PMID- 29046677
TI  - Defining Genome-Wide Expression and Phenotypic Contextual Cues in Macrophages
      Generated by Granulocyte/Macrophage Colony-Stimulating Factor, Macrophage Colony
      Stimulating Factor, and Heat-Killed Mycobacteria.
AB  - Heat-killed (HK) Mycobacterium obuense (NCTC13365) is currently being evaluated
      in the clinic as an immunotherapeutic agent for cancer treatment. Yet, the
      molecular underpinnings underlying immunomodulatory properties of HK M. obuense
      are still largely undefined. To fill this void, we sought to perform
      immunophenotyping, chemokine/cytokine release analysis and genome-wide
      characterization of monocyte-derived macrophages (MDM) in which monocytes were
      originally isolated from healthy donors and differentiated by HK M. obuense (Mob
      MDM) relative to macrophage colony-stimulating factor (M-MDM) and
      granulocyte/macrophage colony-stimulating factor (GM-MDM). Immunophenotyping and
      cytokine release analysis revealed downregulated surface expression of CD36,
      decreased spontaneous release of CCL2 and increased spontaneous secretion of
      CCL5, CXCL8/IL-8, IL-6, and TNF-alpha in Mob-MDM relative to M-MDM and GM-MDM.
      Analysis of cytostatic activity showed that Mob-MDM exhibited similar growth
      inhibitory effects on immortalized and malignant epithelial cells compared with
      GM-MDM but at an elevated rate relative to M-MDM. To understand global cues in
      Mob-MDM, we performed comparative RNA-sequencing (RNA-Seq) analysis of Mob-MDM
      relative to GM-MDM and M-MDM (n = 4 donors). Clustering analysis underscored
      expression profiles (n = 256) that were significantly modulated in Mob-MDM versus
      both M-MDM and GM-MDM including, among others, chemokines/cytokines and their
      receptors, enzymes and transcriptions factors. Topological functional analysis of
      these profiles identified pathways and gene sets linked to Mob-MDM phenotype
      including nitric oxide production, acute phase response signaling and microbe
      recognition pathways as well as signaling cues mediated by the proinflammatory
      cytokine, interferon-gamma, and the intracellular pattern recognition receptor,
      nucleotide-binding oligomerization domain-containing protein 2. Taken together,
      our study highlights molecular immune phenotypes and global signaling cues in Mob
      MDM that may underlie immunomodulatory properties of HK M. obuense. Such
      properties could be of valuable use in immunotherapy approaches such as adoptive
      cell therapy against cancer.

PMID- 29046678
TI  - Kunitz Proteinase Inhibitors Limit Water Stress Responses in White Clover
      (Trifolium repens L.) Plants.
AB  - The response of plants to water deficiency or drought is a complex process, the
      perception of which is triggered at the molecular level before any visible
      morphological responses are detected. It was found that different groups of plant
      proteinase inhibitors (PIs) are induced and play an active role during abiotic
      stress conditions such as drought. Our previous work with the white clover
      (Trifolium repens L.) Kunitz Proteinase Inhibitor (Tr-KPI) gene family showed
      that Tr-KPIs are differentially regulated to ontogenetic and biotic stress
      associated cues and that, at least some members of this gene family may be
      required to maintain cellular homeostasis. Altered cellular homeostasis may also
      affect abiotic stress responses and therefore, we aimed to understand if distinct
      Tr-PKI members function during drought stress. First, the expression level of
      three Tr-KPI genes, Tr-KPI1, Tr-KPI2, and Tr-KPI5, was measured in two cultivars
      and one white clover ecotype with differing capacity to tolerate drought. The
      expression of Tr-KPI1 and Tr-KPI5 increased in response to water deficiency and
      this was exaggerated when the plants were treated with a previous period of water
      deficiency. In contrast, proline accumulation and increased expression of Tr
      NCED1, a gene encoding a protein involved in ABA biosynthesis, was delayed in
      plants that experienced a previous drought period. RNAi knock-down of Tr-KPI1 and
      Tr-KPI5 resulted in increased proline accumulation in leaf tissue of plants grown
      under both well-watered and water-deficit conditions. In addition, increased
      expression of genes involved in ethylene biosynthesis was found. The data
      suggests that Tr-KPIs, particularly Tr-KPI5, have an explicit function during
      water limitation. The results also imply that the Tr-KPI family has different in
      planta proteinase targets and that the functions of this protein family are not
      solely restricted to one of storage proteins or in response to biotic stress.

PMID- 29046679
TI  - Overexpression of NPR1 in Brassica juncea Confers Broad Spectrum Resistance to
      Fungal Pathogens.
AB  - Brassica juncea (Indian mustard) is a commercially important oil seed crop, which
      is highly affected by many biotic stresses. Among them, Alternaria leaf blight
      and powdery mildew are the most devastating diseases leading to huge yield losses
      in B. juncea around the world. In this regard, genetic engineering is a promising
      tool that may possibly allow us to enhance the B. juncea disease resistance
      against these pathogens. NPR1 (non-expressor of pathogen-related gene 1) is a
      bonafide receptor of salicylic acid (SA) which modulates multiple immune
      responses in plants especially activation of induced and systemic acquired
      resistance (SAR). Here, we report the isolation and characterization of new NPR1
      homolog (BjNPR1) from B. juncea. The phylogenetic tree constructed based on the
      deduced sequence of BjNPR1 with homologs from other species revealed that BjNPR1
      grouped together with other known NPR1 proteins of Cruciferae family, and was
      nearest to B. napus. Furthermore, expression analysis showed that BjNPR1 was
      upregulated after SA treatment and fungal infection but not by jasmonic acid or
      abscisic acid. To understand the defensive role of this gene, we generated B.
      juncea transgenic lines overexpressing BjNPR1, and further confirmed by PCR and
      Southern blotting. The transgenic lines showed no phenotypic abnormalities, and
      constitutive expression of BjNPR1 activates defense signaling pathways by priming
      the expression of antifungal PR genes. Moreover, BjNPR1 transgenic lines showed
      enhanced resistance to Alternaria brassicae and Erysiphe cruciferarum as there
      was delay in symptoms and reduced disease severity than non-transgenic plants. In
      addition, the rate of disease spreading to uninfected or distal parts was also
      delayed in transgenic plants thus suggesting the activation of SAR. Altogether,
      the present study suggests that BjNPR1 is involved in broad spectrum of disease
      resistance against fungal pathogens.

PMID- 29046681
TI  - An Automated Method for High-Throughput Screening of Arabidopsis Rosette Growth
      in Multi-Well Plates and Its Validation in Stress Conditions.
AB  - High-throughput plant phenotyping platforms provide new possibilities for
      automated, fast scoring of several plant growth and development traits, followed
      over time using non-invasive sensors. Using Arabidopsis as a model offers
      important advantages for high-throughput screening with the opportunity to
      extrapolate the results obtained to other crops of commercial interest. In this
      study we describe the development of a highly reproducible high-throughput
      Arabidopsis in vitro bioassay established using our OloPhen platform, suitable
      for analysis of rosette growth in multi-well plates. This method was successfully
      validated on example of multivariate analysis of Arabidopsis rosette growth in
      different salt concentrations and the interaction with varying nutritional
      composition of the growth medium. Several traits such as changes in the rosette
      area, relative growth rate, survival rate and homogeneity of the population are
      scored using fully automated RGB imaging and subsequent image analysis. The assay
      can be used for fast screening of the biological activity of chemical libraries,
      phenotypes of transgenic or recombinant inbred lines, or to search for potential
      quantitative trait loci. It is especially valuable for selecting genotypes or
      growth conditions that improve plant stress tolerance.

PMID- 29046680
TI  - Smart Parasitic Nematodes Use Multifaceted Strategies to Parasitize Plants.
AB  - Nematodes are omnipresent in nature including many species which are parasitic to
      plants and cause enormous economic losses in various crops. During the process of
      parasitism, sedentary phytonematodes use their stylet to secrete effector
      proteins into the plant cells to induce the development of specialized feeding
      structures. These effectors are used by the nematodes to develop compatible
      interactions with plants, partly by mimicking the expression of host genes.
      Intensive research is going on to investigate the molecular function of these
      effector proteins in the plants. In this review, we have summarized which
      physiological and molecular changes occur when endoparasitic nematodes invade the
      plant roots and how they develop a successful interaction with plants using the
      effector proteins. We have also mentioned the host genes which are induced by the
      nematodes for a compatible interaction. Additionally, we discuss how nematodes
      modulate the reactive oxygen species (ROS) and RNA silencing pathways in addition
      to post-translational modifications in their own favor for successful parasitism
      in plants.

PMID- 29046682
TI  - Cyclic Nucleotide Monophosphates and Their Cyclases in Plant Signaling.
AB  - The cyclic nucleotide monophosphates (cNMPs), and notably 3',5'-cyclic guanosine
      monophosphate (cGMP) and 3',5'-cyclic adenosine monophosphate (cAMP) are now
      accepted as key signaling molecules in many processes in plants including growth
      and differentiation, photosynthesis, and biotic and abiotic defense. At the
      single molecule level, we are now beginning to understand how cNMPs modify
      specific target molecules such as cyclic nucleotide-gated channels, while at the
      systems level, a recent study of the Arabidopsis cNMP interactome has identified
      novel target molecules with specific cNMP-binding domains. A major advance came
      with the discovery and characterization of a steadily increasing number of
      guanylate cyclases (GCs) and adenylate cyclases (ACs). Several of the GCs are
      receptor kinases and include the brassinosteroid receptor, the phytosulfokine
      receptor, the Pep receptor, the plant natriuretic peptide receptor as well as a
      nitric oxide sensor. We foresee that in the near future many more molecular
      mechanisms and biological roles of GCs and ACs and their catalytic products will
      be discovered and further establish cNMPs as a key component of plant responses
      to the environment.

PMID- 29046683
TI  - The Diversity of Sequence and Chromosomal Distribution of New Transposable
      Element-Related Segments in the Rye Genome Revealed by FISH and Lineage
      Annotation.
AB  - Transposable elements (TEs) in plant genomes exhibit a great variety of
      structure, sequence content and copy number, making them important drivers for
      species diversity and genome evolution. Even though a genome-wide statistic
      summary of TEs in rye has been obtained using high-throughput DNA sequencing
      technology, the accurate diversity of TEs in rye, as well as their chromosomal
      distribution and evolution, remains elusive due to the repetitive sequence
      assembling problems and the high dynamic and nested nature of TEs. In this study,
      using genomic plasmid library construction combined with dot-blot hybridization
      and fluorescence in situ hybridization (FISH) analysis, we successfully isolated
      70 unique FISH-positive TE-related sequences including 47 rye genome specific
      ones: 30 showed homology or partial homology with previously FISH characterized
      sequences and 40 have not been characterized. Among the 70 sequences, 48
      sequences carried Ty3/gypsy-derived segments, 7 sequences carried Ty1/copia
      derived segments and 15 sequences carried segments homologous with multiple TE
      families. 26 TE lineages were found in the 70 sequences, and among these
      lineages, Wilma was found in sequences dispersed in all chromosome regions except
      telomeric positions; Abiba was found in sequences predominantly located at
      pericentromeric and centromeric positions; Wis, Carmilla, and Inga were found in
      sequences displaying signals dispersed from distal regions toward pericentromeric
      positions; except DNA transposon lineages, all the other lineages were found in
      sequences displaying signals dispersed from proximal regions toward distal
      regions. A high percentage (21.4%) of chimeric sequences were identified in this
      study and their high abundance in rye genome suggested that new TEs might form
      through recombination and nested transposition. Our results also gave proofs that
      diverse TE lineages were arranged at centromeric and pericentromeric positions in
      rye, and lineages like Abiba might play a role in their structural organization
      and function. All these results might help in understanding the diversity and
      evolution of TEs in rye, as well as their driving forces in rye genome
      organization and evolution.

PMID- 29046684
TI  - Novel Insights into miRNA Regulation of Storage Protein Biosynthesis during Wheat
      Caryopsis Development under Drought Stress.
AB  - Drought stress is a significant abiotic stress factor that affects wheat yield
      and quality. MicroRNA (miRNA) plays an important role in regulating caryopsis
      development in response to drought stress. However, little is known about the
      expression characteristics of miRNAs and how they regulate protein accumulation
      in wheat caryopsis under drought stress. To address this, two small RNA libraries
      of wheat caryopsis under control and drought stress conditions were constructed
      and sequenced. A total of 125 miRNAs were identified in the two samples, of which
      110 were known and 15 were novel. A total of 1,981 miRNA target genes were
      predicted and functional annotations were obtained from various databases for
      1,641 of them. Four miRNAs were identified as differential expression under
      drought stress, and the expression patterns of three of them were consistent with
      results obtained by reverse transcription polymerase chain reaction (RT-PCR) and
      reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover,
      three miRNA-target pairs showed negative regulation tendency, as revealed by RT
      qPCR. Functional enrichment and pathway analysis revealed that four pathways
      might be involved in storage protein biosynthesis. Furthermore, drought stress
      significantly increased the accumulation of protein bodies and protein content in
      wheat endosperm. In summary, our findings suggest that drought stress may enhance
      storage protein by regulating the expression of miRNAs and their target genes.

PMID- 29046685
TI  - Comparative Analysis of the Complete Plastomes of Apostasia wallichii and
      Neuwiedia singapureana (Apostasioideae) Reveals Different Evolutionary Dynamics
      of IR/SSC Boundary among Photosynthetic Orchids.
AB  - Apostasioideae, consists of only two genera, Apostasia and Neuwiedia, which are
      mainly distributed in Southeast Asia and northern Australia. The floral
      structure, taxonomy, biogeography, and genome variation of Apostasioideae have
      been intensively studied. However, detailed analyses of plastome composition and
      structure and comparisons with those of other orchid subfamilies have not yet
      been conducted. Here, the complete plastome sequences of Apostasia wallichii and
      Neuwiedia singapureana were sequenced and compared with 43 previously published
      photosynthetic orchid plastomes to characterize the plastome structure and
      evolution in the orchids. Unlike many orchid plastomes (e.g., Paphiopedilum and
      Vanilla), the plastomes of Apostasioideae contain a full set of 11 functional
      NADH dehydrogenase (ndh) genes. The distribution of repeat sequences and simple
      sequence repeat elements enhanced the view that the mutation rate of non-coding
      regions was higher than that of coding regions. The 10 loci-ndhA intron, matK
      5'trnK, clpP-psbB, rps8-rpl14, trnT-trnL, 3'trnK-matK, clpP intron, psbK-trnK,
      trnS-psbC, and ndhF-rpl32-that had the highest degrees of sequence variability
      were identified as mutational hotspots for the Apostasia plastome. Furthermore,
      our results revealed that plastid genes exhibited a variable evolution rate
      within and among different orchid genus. Considering the diversified evolution of
      both coding and non-coding regions, we suggested that the plastome-wide evolution
      of orchid species was disproportional. Additionally, the sequences flanking the
      inverted repeat/small single copy (IR/SSC) junctions of photosynthetic orchid
      plastomes were categorized into three types according to the presence/absence of
      ndh genes. Different evolutionary dynamics for each of the three IR/SSC types of
      photosynthetic orchid plastomes were also proposed.

PMID- 29046686
TI  - Combining Fungicides and Prospective NPR1-Based "Just-in-Time" Immunomodulating
      Chemistries for Crop Protection.
AB  - Each year, crop yield is lost to weeds competing for resources, insect herbivory
      and diseases caused by pathogens. To thwart these insults and preserve yield
      security and a high quality of traits, conventional agriculture makes use of
      improved cultivars combined with fertilizer and agrochemical applications.
      However, given that regulatory bodies and consumers are demanding environmentally
      safer agrochemicals, while at the same time resistance to agrochemicals is
      mounting, it is crucial to adopt a "holistic" approach to agriculture by not
      excluding any number of management tools at our disposal. One such tool includes
      chemicals that stimulate plant immunity. The development of this particular type
      of alternative crop protection strategy has been of great interest to us. We have
      approached this paradigm by studying plant immunity, specifically systemic
      acquired resistance (SAR). The deployment of SAR immunity requires the production
      by the crop plant of an endogenous small molecule metabolite called salicylic
      acid (SA). Furthermore, immunity can only be deployed if SA can bind to its
      receptor and activate the genes responsible for the SAR program. The key receptor
      for SAR is a transcription coactivator called NPR1. Since discovering this NPR1
      SA receptor-ligand pair, we have embarked on a journey to develop novel
      chemistries capable of deploying SAR in the field. The journey begins with the
      development of a scalable assay to identify these novel chemistries. One such
      assay, presented here, is based on differential scanning fluorimetry technology
      and demonstrates that NPR1 is destabilized by binding to SA.

PMID- 29046687
TI  - How Do Plants and Phytohormones Accomplish Heterophylly, Leaf Phenotypic
      Plasticity, in Response to Environmental Cues.
AB  - Plant species are known to respond to variations in environmental conditions.
      Many plant species have the ability to alter their leaf morphology in response to
      such changes. This phenomenon is termed heterophylly and is widespread among land
      plants. In some cases, heterophylly is thought to be an adaptive mechanism that
      allows plants to optimally respond to environmental heterogeneity. Recently, many
      research studies have investigated the occurrence of heterophylly in a wide
      variety of plants. Several studies have suggested that heterophylly in plants is
      regulated by phytohormones. Herein, we reviewed the existing knowledge on the
      relationship and role of phytohormones, especially abscisic acid, ethylene,
      gibberellins, and auxins (IAA), in regulating heterophylly and attempted to
      elucidate the mechanisms that regulate heterophylly.

PMID- 29046689
TI  - An Updated Protocol for High Throughput Plant Tissue Sectioning.
AB  - Quantification of the tissue and cellular structure of plant material is
      essential for the study of a variety of plant sciences applications. Currently,
      many methods for sectioning plant material are either low throughput or involve
      free-hand sectioning which requires a significant amount of practice. Here, we
      present an updated method to provide rapid and high-quality cross sections,
      primarily of root tissue but which can also be readily applied to other tissues
      such as leaves or stems. To increase the throughput of traditional agarose
      embedding and sectioning, custom designed 3D printed molds were utilized to embed
      5-15 roots in a block for sectioning in a single cut. A single fluorescent stain
      in combination with laser scanning confocal microscopy was used to obtain high
      quality images of thick sections. The provided CAD files allow production of the
      embedding molds described here from a number of online 3D printing services.
      Although originally developed for roots, this method provides rapid, high quality
      cross sections of many plant tissue types, making it suitable for use in forward
      genetic screens for differences in specific cell structures or developmental
      changes. To demonstrate the utility of the technique, the two parent lines of the
      wheat (Triticum aestivum) Chinese Spring * Paragon doubled haploid mapping
      population were phenotyped for root anatomical differences. Significant
      differences in adventitious cross section area, stele area, xylem, phloem,
      metaxylem, and cortical cell file count were found.

PMID- 29046688
TI  - Global Analysis of Small RNA Dynamics during Seed Development of Picea glauca and
      Arabidopsis thaliana Populations Reveals Insights on their Evolutionary
      Trajectories.
AB  - While DNA methylation carries genetic signals and is instrumental in the
      evolution of organismal complexity, small RNAs (sRNAs), ~18-24 ribonucleotide
      (nt) sequences, are crucial mediators of methylation as well as gene silencing.
      However, scant study deals with sRNA evolution via featuring their expression
      dynamics coupled with species of different evolutionary time. Here we report an
      atlas of sRNAs and microRNAs (miRNAs, single-stranded sRNAs) produced over time
      at seed-set of two major spermatophytes represented by populations of Picea
      glauca and Arabidopsis thaliana with different seed-set duration. We applied
      diverse profiling methods to examine sRNA and miRNA features, including size
      distribution, sequence conservation and reproduction-specific regulation, as well
      as to predict their putative targets. The top 27 most abundant miRNAs were highly
      overlapped between the two species (e.g., miR166,-319 and-396), but in P. glauca,
      they were less abundant and significantly less correlated with seed-set phases.
      The most abundant sRNAs in libraries were deeply conserved miRNAs in the plant
      kingdom for Arabidopsis but long sRNAs (24-nt) for P. glauca. We also found
      significant difference in normalized expression between populations for
      population-specific sRNAs but not for lineage-specific ones. Moreover, lineage
      specific sRNAs were enriched in the 21-nt size class. This pattern is consistent
      in both species and alludes to a specific type of sRNAs (e.g., miRNA, tasiRNA)
      being selected for. In addition, we deemed 24 and 9 sRNAs in P. glauca and
      Arabidopsis, respectively, as sRNA candidates targeting known adaptive genes.
      Temperature had significant influence on selected gene and miRNA expression at
      seed development in both species. This study increases our integrated
      understanding of sRNA evolution and its potential link to genomic architecture
      (e.g., sRNA derivation from genome and sRNA-mediated genomic events) and
      organismal complexity (e.g., association between different sRNA expression and
      their functionality).

PMID- 29046690
TI  - ALA6, a P4-type ATPase, Is Involved in Heat Stress Responses in Arabidopsis
      thaliana.
AB  - Maintaining lipid membrane integrity is an essential aspect of plant tolerance to
      high temperature. P4-type ATPases are responsible for flipping and stabilizing
      asymmetric phospholipids in membrane systems, though their functions in stress
      tolerance are not entirely clear. Aminophospholipid ATPase6 (ALA6) is a member of
      the P4-type ATPase family, which has 12 members in Arabidopsis thaliana. Here, we
      show that a loss-of-function mutant of ALA6 (ala6) exhibits clear sensitivity to
      heat stress, including both basal and acquired thermotolerance treatments.
      Overexpression of ALA6 improves seedling resistance to heat stress, while mutated
      ALA6 transgenic plants, in which the conserved functional site of the ALA family
      has a point mutation, are still susceptible to heat stress like ala6 loss-of
      function mutant. In addition, ala6 displays higher ion-leakage during heat
      treatment, suggesting that the lipid flippase activity of ALA6 plays a vital role
      in heat stress responses. Transcriptome analysis reveals differences in gene
      expression between ala6 and wild-type plants with or without heat stress. The
      differentially expressed genes are involved primarily in the physiological
      processes of stress response, cellular compartment maintenance, macromolecule
      stability and energy production. Our results suggest that ALA6 is crucial for the
      stability of membrane when plants suffer from high temperature stress.

PMID- 29046691
TI  - Effect on Growth, Photosynthesis, and Oxidative Stress of Single Walled Carbon
      Nanotubes Exposure to Marine Alga Dunaliella tertiolecta.
AB  - Single walled carbon nanotubes were carboxylated by microwave assisted acid
      oxidation (f-SWCNTs) and examined for their ecotoxicity on marine alga
      chlorophyte Dunaliella tertiolecta. Toxicity was evaluated based on growth,
      photosynthetic activities, oxidative stress, and intracellular glutathione in the
      concentration range of 0.1-20 mg/L f-SWCNT. Physical interactions between the f
      SWCNT and alga were examined using light microscopy and scanning electron
      microscope. Increasing the nanotube concentration increased the toxic effects
      where growth inhibition was as high as 30%, photosynthetic yield decreased by as
      much as 18%, and intracellular glutathione reduction reached 95%. The results
      from f-SWCNTs were somewhat different when compared to our previous study using
      the same algae and functionalized multiwalled carbon nanotubes, where exposure
      led to longer lag phase and higher growth rate inhibition.

PMID- 29046692
TI  - A patient with van Maldergem syndrome with endocrine abnormalities,
      hypogonadotropic hypogonadism, and breast aplasia/hypoplasia.
AB  - BACKGROUND: We report a female patient with endocrine abnormalities,
      hypogonadotropic hypogonadism and amazia (breasts aplasia/hypoplasia but normal
      nipples and areolas) in a rare syndrome: Van Maldergem syndrome (VMS). CASE
      PRESENTATION: Our patient was first evaluated at age 4 for intellectual
      disability, craniofacial features, and auditory malformations. At age 15, she
      presented with no breast development and other findings consistent with
      hypogonadotropic hypogonadism. At age 37, she underwent whole exome sequencing
      (WES) to identify pathogenic variants. WES revealed compound heterozygous
      variants in DCHS1 (rs145099391:G > A, p.P197L & rs753548138:G > A, p.T2334 M)
      [RefSeq NM_003737.3], diagnostic of Van Maldergem syndrome (VMS-1). VMS is a rare
      autosomal disorder reported in only 13 patients, characterized by intellectual
      disability, typical craniofacial features, auditory malformations, hearing loss,
      skeletal and limb malformations, brain abnormalities with periventricular
      neuronal heterotopia and other variable anomalies. Our patient had similar
      phenotypic abnormalities. She also had hypogonadotropic hypogonadism and amazia.
      Based on the clinical findings reported, two previously published patients with
      VMS may also have been affected by hypogonadotropic hypogonadism, but endocrine
      abnormalities were not evaluated or mentioned. CONCLUSION: This case highlights
      an individual with VMS, characterized by compound heterozygous variants in DCHS1.
      Our observations may provide additional information on the phenotypic spectrum of
      VMS, including hypogonadotropic hypogonadism and amazia. However, the molecular
      genetic basis for endocrine anomalies observed in some VMS patients, including
      ours, remains unexplained.

PMID- 29046693
TI  - Antibacterial activity of essential oil from lavender (Lavandula angustifolia)
      against pet turtle-borne pathogenic bacteria.
AB  - Pet turtles are well-known to harbor an array of bacterial pathogens which can
      cause zoonotic infections in humans as well as opportunistic infections in the
      turtles itself. Essential oils are the natural plant extracts which have been
      traditionally used for disease treatment. In the present study, the essential oil
      of lavender (EOL) was examined for its antibacterial activity against thirty
      eight strains of turtle-borne pathogenic bacteria belonging to seven species;
      Aeromonas hydrophila, A. caviae, A. dhakensis, Citrobacter freundii, Proteus
      mirabilis, Salmonella enterica and Pseudomonas aeruginosa. Antibacterial activity
      of EOL was tested by means of disk diffusion, minimum inhibitory concentration
      (MIC), and minimum bactericidal concentration (MBC) tests. In addition, the
      antimicrobial susceptibility pattern of 11 commonly used antimicrobials was
      examined and the multiple antibiotic resistance (MAR) index was calculated. The
      results revealed that EOL was active against all tested turtle-borne pathogenic
      bacteria except P. aeruginosa. The range of MIC and MBC values of EOL against
      isolates except P. aeruginosa were recorded as 0.5-1% (V/V) and 0.5-2% (V/V),
      respectively. The MBC/MIC ratio was detected as <4, revealing that the tested EOL
      was bactericidal. Besides, most of the isolates were resistant to different
      antimicrobials in antimicrobial disk diffusion test. MAR index values of the
      tested strains were ranging from 0.27 to 0.91. The outcomes indicate that EOL has
      a potential to be used as an antibacterial agent against pathogenic bacteria
      isolated from pet turtles.

PMID- 29046694
TI  - Hyperglycemia exacerbates downregulation of dynamin-like protein 1 in ischemic
      cerebral injury.
AB  - Ischemic stroke is one of the leading causes of adult disability and death.
      Hyperglycemia is associated with an increased risk of stroke and poor outcomes
      after brain injury. Dynamin-like protein I (DLP-1) regulates mitochondrial
      fission and promotes mitochondrial dynamics. Neurodegenerative diseases are
      associated with mitochondrial dysfunction, and the downregulation of DLP-1 has
      been previously identified in a stroke animal model. Here, we investigated the
      changes in DLP-1 protein expression in an animal model of focal cerebral ischemia
      with induced hyperglycemia. Streptozotocin (40 mg/kg) was intraperitoneally
      injected into male rats to induce hyperglycemia, and middle cerebral artery
      occlusion (MCAO) was surgically induced 4 weeks after streptozotocin treatment.
      Brain tissue was isolated 24 hours after MCAO, and cerebral cortex samples were
      used for this study. Proteomics revealed a decrease in DLP-1 expression in MCAO
      animals when compared with controls, and this downregulation was more prominent
      in MCAO animals with hyperglycemia. Reverse-transcription polymerase chain
      reaction and Western blot analyses confirmed that DLP-1 was significantly
      downregulated in MCAO-injured animals with hyperglycemia compared to those
      without hyperglycemia. The decrease in DLP-1 indicates mitochondrial
      morphological changes and dysfunction. Together, these results suggest that the
      severe decrease of DLP-1 seen after brain injury under hyperglycemic conditions
      may exacerbate the damage to the brain.

PMID- 29046695
TI  - Artemisia argyi attenuates airway inflammation in lipopolysaccharide induced
      acute lung injury model.
AB  - Artemisia argyi is used as a health supplement, tea, and food source in Korea.
      This study aimed to evaluate the effect of Artemisia argyi (AA) and its active
      compound, dehydromatricarin A (DA), on the attenuation of airway inflammation in
      a murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). The
      C57BL/6 mice were administered AA (50 mg/kg or 100 mg/kg) and DA (10 mg/kg or 20
      mg/kg) by oral gavage from day 0 to 7 days and LPS treated by intranasal
      instillation 48 hours before the sacrifice. The treatment of AA and DA markedly
      decreased inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared
      with that in ALI-induced mice, which was accompanied by a significant reduction
      in the levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in
      BALF. Furthermore, the administration of AA and DA clearly decreased inducible
      nitric oxide synthase (iNOS) expression and nuclear factor kappa B (NF-kappaB)
      phosphorylation in comparison with that in the ALI-induced mice. The histological
      examination of the lung tissue revealed that the administration of AA and DA
      suppressed the inflammatory cell infiltration into the peribronchial and alveolar
      lesions induced by LPS instillation. Collectively, our results indicated that AA
      and DA effectively decreased the airway inflammatory response induced by LPS
      instillation. Therefore, AA and DA may offer a potential therapy for airway
      inflammatory disease.

PMID- 29046696
TI  - Early changes in retinal structure and BMP2 expression in the retina and
      crystalline lens of streptozotocin-induced diabetic pigs.
AB  - PURPOSE: This study aims to evaluate early changes in retinal structure and BMP2
      expression in the retina and crystalline lens by comparing streptozotocin-induced
      diabetic pigs and normal control group pigs. METHODS: Five eye samples from five
      diabetic Micro-pigs (Medikinetics, Pyeongtaek, Korea) and five eye samples from
      five control pigs bred in a specific pathogen-free area were used. Diabetes was
      developed through intravenous injection of nicotinamide and streptozotocin, and
      the average fasting glucose level was maintained at 250 mg/dL or higher for 16
      weeks. To evaluate BMP2 expression in the retina and crystalline lens, Western
      blotting was performed. RESULTS: In Hematoxylin and Eosin staining, most diabetic
      pigs showed structural abnormalities in the inner plexiform layer. The number of
      nuclei in the ganglion cell layer within the range of 104 um2 was 3.78+/-0.60 for
      diabetic pigs and 5.57+/-1.07 for control group pigs, showing a statistically
      significant difference. In immunohistochemical staining, diabetic retinas showed
      an overall increase in BMP2 expression. In Western blotting, the average
      BMP2/actin level of diabetic retinas was 1.19+/-0.05, showing a significant
      increase compared to the 1.06+/-0.03 of the control group retinas (P=0.016). The
      BMP2/actin level of diabetic crystalline lenses was similar to the control group
      crystalline lenses (P=0.730). CONCLUSIONS: Compared to control group pigs, the
      number of nuclei in the inner nuclear layer of retinas from streptozotocin
      induced diabetic pigs decreased, while an increase in BMP2 expression was
      observed in the retina of diabetic pigs.

PMID- 29046697
TI  - Preclinical safety assessment of Angelica acutiloba using a 13-week repeated dose
      oral toxicity study in rats.
AB  - Angelica acutiloba (AA), a Japanese species of Danggui, has been used worldwide
      as a traditional herbal medicine with several bioactivities including anti
      diabetic, anti-allergic, anti-inflammatory, anti-tumor, and anti-obesity.
      However, there is lack of toxicological data available to evaluate potential long
      term toxicity and the no-observed-adverse-effect level (NOAEL) of AA extract in
      accordance with the test guidelines published by the Organization for Economic
      Cooperation and Development. In the 14-day repeat-dose toxicity study, no adverse
      effects on mortality, body weight change, clinical signs, and organ weights was
      found following repeat oral administration to rats for 14 days (125, 250, 500,
      1000, and 2000 mg/kg body weight), leading that 2000 mg/kg is the highest
      recommended dose of AA extract for the 13-week repeat-dose oral toxicity study.
      In the 13-week repeat-dose oral toxicity study, the AA extract was orally
      administered to groups of rats for 13 weeks (125, 250, 500, 1000, and 2000 mg/kg
      body weight) to compare between control and AA extract groups. The administration
      of AA extract did not produce mortality or remarkable clinical signs during this
      13-week study. And, the data revealed that there were no significant differences
      in food/water consumption, body weight, hematological parameters, clinical
      chemistry parameters, gross macroscopic findings, organ weight and histopathology
      in comparison to the control group. On the basis of these results, the subchronic
      NOAEL of the AA extract was more than 2000 mg/kg/day when tested in rats. And,
      the AA extract is considered safe to use orally as a traditional herbal medicine.

PMID- 29046698
TI  - Evaluation of in vitro and in vivo genotoxicity of Angelica acutiloba in a
      standard battery of assays.
AB  - Among three representative species of Angelica found in Asian countries,
      including Korea, China, and Japan, Angelica acutiloba (AA) has been used as
      traditional herbal medicine with antitumor, anti-inflammatory, anti-obesity, and
      anti-diabetes activities. In this study, the potential genotoxicity and
      mutagenicity of the AA extract were examined in a battery of in vitro and in vivo
      tests (bacterial reverse mutation assay, in vitro chromosomal aberrations assay,
      and in vivo micronucleus assay) in accordance with the test guidelines for
      toxicity testing developed by the Organization for Economic Cooperation and
      Development. Upon testing in the bacterial mutation assay (Ames test) using five
      Salmonella typhimurium TA98, TA100, TA102, TA1535 and TA1537, no significant
      increase the number of revertant colonies in the metabolic activation system and
      non-activation system was noted in the AA extract groups. Also, in the chromosome
      aberration test, the AA extract did not cause chromosomal aberration with or
      without metabolic activation by S9 mix. A bone marrow micronucleus test of mice
      demonstrated that the incidence of micronucleated polychromatic erythrocytes in
      the AA extract groups (500, 1000 and 2000 mg/kg BW) was equivalent to that of the
      negative control group. Based on these results from a standard battery of assays,
      the AA extract was concluded to have no genotoxic at the proper dose.

PMID- 29046700
TI  - Cerebral ischemic injury decreases alpha-synuclein expression in brain tissue and
      glutamate-exposed HT22 cells.
AB  - alpha-Synuclein is abundantly expressed in neuronal tissue, plays an essential
      role in the pathogenesis of neurodegenerative disorders, and exerts a
      neuroprotective effect against oxidative stress. Cerebral ischemia causes severe
      neurological disorders and neuronal dysfunction. In this study, we examined alpha
      synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral
      ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical
      operation was performed on male Sprague-Dawley rats, and brain samples were
      isolated 24 hours after MCAO. We confirmed neurological behavior deficit,
      infarction area, and histopathological changes following MCAO injury. A proteomic
      approach and Western blot analysis demonstrated a decrease in alpha-synuclein in
      the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced
      neuronal cell death and decreased alpha-synuclein expression in a hippocampal
      derived cell line in a dose-dependent manner. It is known that alpha-synuclein
      regulates neuronal survival, and low levels of alpha-synuclein expression result
      in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads
      to a reduction in alpha-synuclein and consequently causes serious brain damage.

PMID- 29046699
TI  - Age-dependent differences in myelin basic protein expression in the hippocampus
      of young, adult and aged gerbils.
AB  - Myelin degeneration is one of the characteristics of aging and degenerative
      diseases. This study investigated age-related alterations in expression of myelin
      basic protein (MBP) in the hippocampal subregions (dentate gyrus, CA2/3 and CA1
      areas) of gerbils of various ages; young (1 month), adult (6 months) and aged (24
      months), using western blot and immunohistochemistry. Western blot results showed
      tendencies of age-related reductions of MBP levels. MBP immunoreactivity was
      significantly decreased with age in synaptic sites of trisynaptic loops,
      perforant paths, mossy fibers, and Schaffer collaterals. In particular, MBP
      immunoreactive fibers in the dentate molecular cell layer (perforant path) was
      significantly reduced in adult and aged subjects. In addition, MBP immunoreactive
      mossy fibers in the dentate polymorphic layer and in the CA3 striatum radiatum
      was significantly decreased in the aged group. Furthermore, we observed similar
      age-related alterations in the CA1 stratum radiatum (Schaffer collaterals).
      However, the density of MBP immunoreactive fibers in the dentate granular cell
      layer and CA stratum pyramidale was decreased with aging. These findings indicate
      that expression of MBP is age-dependent and tissue specific according to
      hippocampal layers.

PMID- 29046701
TI  - Safety of 8-weeks oral administration of Arctium lappa L.
AB  - Recently, worldwide dietary reference intakes have been considered an important
      guideline for public health. Some governments and the World Health Organization
      (WHO) provide guidelines concerning dietary intake. Although an ingredient may
      have a history of use as a culinary material, changes in the environment over
      time suggest that the acceptable maximum intake each of food/culinary material
      should be regularly evaluated. Arctium lappa L. has been used as a culinary
      material for many centuries in Korea and Japan and some recent studies have
      reported related therapeutic effects. However, there are no reports on the safety
      of repeated oral administration. In this study, we evaluated the safety of a 8
      weeks repeated oral intake of A. lappa. We concluded that treatment with <250
      mg/kg A. lappa, which was within the safety range, resulted in body weight
      decrease and blood glucose suppression.

PMID- 29046702
TI  - In vivo validation of metastasis-regulating microRNA-766 in human triple-negative
      breast cancer cells.
AB  - Breast cancer is the second most common cancer and the most frequent cancer in
      women worldwide. Recent improvements in early detection and effective adjuvant
      chemotherapies have improved the survival of breast cancer patients. Even with
      initial disease remission, one-third of all breast cancer patients will relapse
      with distant metastasis. Breast cancer metastasis is largely an incurable disease
      and the main cause of death among breast cancer patients. Cancer metastasis is
      comprised of complex processes that are usually not controllable by intervention
      of a single molecular target. As a single microRNA (miRNA) can affect the
      aggressiveness of breast cancer cells by concurrently modulating multiple pathway
      effectors, a metastasis-regulating miRNA would represent a good disease target
      candidate. In this study, we evaluated the functional capacity of a newly defined
      human metastasis-related miRNA, miR-766, which was previously identified by
      comparing a patient-derived xenograft primary tumor model and a metastasis model.
      Compared to vector-transfected control cells, miR-766-overexpressed triple
      negative breast cancer cells exhibited similar primary tumor growth in the
      orthotopic xenograft model. In contrast, tumor sphere formation and Matrigel
      invasion were significantly decreased in miR-766-overexpressed breast cancer
      cells compared with control cancer cells. In addition, lung metastasis was
      dramatically reduced in miR-766-overexpressed breast cancer cells compared with
      control cells. Thus, miR-766 affected the distant metastasis process to a greater
      extent than cancer cell proliferation and primary tumor growth, and may represent
      a future therapeutic target to effectively control fatal breast cancer
      metastasis.

PMID- 29046703
TI  - Dose-dependent effects of busulfan on dog testes in preparation for
      spermatogonial stem cell transplantation.
AB  - Successful male germ cell transplantation requires depletion of the host germ
      cells to allow efficient colonization of the donor spermatogonial stem cells.
      Although a sterilizing drug, busulfan, is commonly used for the preparation of
      recipient models before transplantation, the optimal dose of this drug has not
      yet been defined in dogs. In this study, 1-year-old mongrel dogs were
      intravenously injected with three different concentrations of busulfan (10, 15,
      or 17.5 mg/kg). Four weeks after busulfan treatment, no fully matured spermatozoa
      were detected in any of the busulfan-treated groups. However, small numbers of
      PGP9.5-positive spermatogonia were detected in all treatment groups, although no
      synaptonemal complex protein-3-positive spermatocytes were detected. Of note,
      acrosin-positive spermatids were not detected in the dogs treated with 15 or 17.5
      mg/kg busulfan, but were detected in the other group. Eight weeks after busulfan
      treatment, the dogs treated with 10 mg/kg busulfan fully recovered, but those in
      the other groups did not. PGP9.5-positive spermatogonia were detected in the 10
      mg/kg group, and at a similar level as in the control group, but these cells were
      rarely detected in the 15 and 17.5 mg/kg groups. These results suggest that a
      dose of 15-17.5 mg/kg is optimal for ablative treatment with busulfan to prepare
      the recipient dogs for male germ cell transplantation. At least eight weeks
      should be allowed for recovery. The results of this study might facilitate the
      production of recipient dogs for male germ cell transplantation and can also
      contribute to studies on chemotherapy.

PMID- 29046704
TI  - Lipolytic effect of novel extracts from mulberry (Morus alba) leaves fermented
      with Cordyceps militaris in the primary adipocytes derived from SD rats.
AB  - Mulberry (Morus alba) leaves are known to have therapeutic effects on lipid
      metabolism including lipogenesis, lipolysis and hyperlipidemia. However, novel
      compounds with strong lipolytic ability among 27 extracts of the mulberry leaves
      fermented with Cordyceps militaris (EMfCs) have not yet been identified.
      Therefore, the cAMP concentration and cell viability were measured in the primary
      adipocytes of SD (Sprague Dawley) rats and 3T3-L1 cells after treatment of 27
      EMfCs. Briefly, mulberry leaves powders amended with three different
      concentrations (0, 25 and 50%) of silkworm pupae (SWP) powder were fermented with
      10% C. militaris (v/w) during three different periods (3, 4 and 6 weeks). A total
      of 27 extracts were obtained from the fermented mulberry leaves powders using
      three different solvents (dH2O, 50% EtOH and 95% EtOH). Among the 27 EMfCs
      treated groups, a significant increase in the concentration of cAMP was detected
      in primary adipocytes treated with 10 extracts when compared with the Vehicle
      treated group. However, their cAMP concentration did not agree completely with
      the non-toxicity, although most extracts showed non-toxicity. Furthermore, the
      concentration of cAMP and level of free glycerol gradually increased in a dose
      dependent manner (100, 200 and 400 ug/mL) of 4M3-95 contained cordycepin without
      any significant toxicity. Overall, the results of this study provide strong
      evidence that 4M3-95 extract derived from EMfCs can stimulate the lipolysis of
      primary adipocytes at an appropriate concentration and therefore have the
      potential for use as lipolytic agents to treat obesity.

PMID- 29046705
TI  - Super pregnancy in a BALB/c mouse superovulated with PMSG.
AB  - This paper reports a case of super pregnancy in a BALB/c mouse pregnant with 30
      pups following induction of superovulation using a PMSG-hCG protocol.
      Superovulation was induced in 10 mice by injecting 5 IU PMSG followed by 5 IU hCG
      48 hours later. Immediately after injection of hCG, animals were placed with
      males at a ratio of 1 to 1 for 24 hours. On day 14 after mating, animals were
      killed by cervical dislocation and the uterus was examined for pregnancy and the
      number of fetuses. The mean (+/-SEM) number of fetuses observed in ten mice was
      5.4+/-3.18 with an unexpectedly super pregnant mouse bearing 30 fetuses on day 14
      of pregnancy.

PMID- 29046706
TI  - Don't call me a leader, but I am one: The Dutch mayor and the tradition of
      bridging-and-bonding leadership in consensus democracies.
AB  - In some democratic contexts, there is a strong aversion to the directive,
      individualistic and masculine expressions of leadership that have come to
      dominate the study of political leadership. Such leadership is antithetical to
      consensus democracies in parts of continental Europe, where the antipathy to
      leadership has linguistic, institutional as well as cultural dimensions.
      Political-administrative and socio-cultural contexts in these countries provide
      little room for heroic expressions of leadership. Consequently, alternative forms
      of leadership and associated vocabularies have developed that carry profound
      practical relevance but that have remained underexplored. Based on an in-depth
      mixed-methods study, this article presents the Dutch mayoralty as an insightful
      and exemplary case of what can be called 'bridging-and-bonding leadership'; it
      provides a clear illustration of how understandings of democratic leadership can
      deviate from the dominant paradigm and of how leading in a consensus context
      brings about unique practical challenges for office holders. The analysis shows
      that the important leadership task of democratic guardianship that is performed
      by Dutch mayors is in danger of being overlooked by scholars of political
      leadership, as are consensus-oriented leadership roles in other parts of the
      world. For that reason, a recalibration of the leadership concept is needed,
      developing an increased theoretical sensitivity towards the non-decisive and
      process-oriented aspects of the leadership phenomenon. This article specifies how
      the future study of leadership, as a part of the change that is advocated, can
      benefit from adopting additional languages of leadership.

PMID- 29046707
TI  - Comparative cytogenetic analysis of marine Palaemon species reveals a
      X1X1X2X2/X1X2Y sex chromosome system in Palaemon elegans.
AB  - BACKGROUND: The maintenance of species and the promotion of speciation are
      closely related to chromosomal rearrangements throughout evolution. Decapoda
      represents the most species-rich order among crustaceans and, despite its
      ecological and economic importance, little is known about decapod karyology. We
      aim at cytogenetically characterizing two sympatric prawn species. RESULTS:
      Analysis of mitotic metaphases and meiotic diakinesis of the common prawn
      Palaemon serratus and the rockpool prawn P. elegans, revealed considerable
      differences between their karyotypes including chromosome numbers and sex
      determination systems. The cytogenetic data for P. serratus showed a diploid
      number of 56 and the putative absence of heteromorphic sex chromosomes. However,
      the diploid chromosome number in P. elegans was 90 for females and 89 for males.
      The karyotype of the females consisted of the three largest acrocentric pairs and
      42 submetacentric and metacentric pairs, while the karyotype of the males
      comprised a clearly identifiable large metacentric chromosome and two acrocentric
      pairs as well as the smaller 42 pairs. These results highlight the presence of
      the X1X1X2X2/X1X2Y multiple sex chromosome system in P. elegans, which constitute
      the only sexual system for Decapoda reported cytogenetically using modern
      techniques. The origin of this sex chromosome system is discussed. We hypothesize
      that the chromosome evolution within the genus could involve several fusion
      events giving rise to a reduction on the chromosome number in P. serratus. In
      both species, the major ribosomal genes were located in two chromosome pairs and
      hybridization signals of the telomeric sequences (TTAGGG)n were visualized at the
      telomeres of all chromosomes. C-banding revealed that, when present, constitutive
      heterochromatin had a predominantly telomeric distribution and no centromeric
      constitutive heterochromatin was observed. CONCLUSIONS: Although more comparative
      cytogenetic analyses are needed to clarify our hypotheses, the findings of this
      work indicate that the prawns of the genus Palaemon represent a promising model
      among Decapoda representatives to investigate the karyotype evolution and the
      patterns of sex chromosome differentiation.

PMID- 29046708
TI  - Improved method for genomic DNA extraction for Opuntia Mill. (Cactaceae).
AB  - BACKGROUND: Genomic DNA extracted from species of Cactaceae is often contaminated
      with significant amounts of mucilage and pectin. Pectin is one of the main
      components of cellular walls, whereas mucilage is a complex polysaccharide with a
      ramified structure. Thus, pectin- and mucilage-free extraction of DNA is a key
      step for further downstream PCR-based analyses. RESULTS: We tested our DNA
      extraction method on cladode tissue (juvenile, adult, and herbaria exemplars) of
      17 species of Opuntia Mill., which are characterized by a large quantity of
      pectin and mucilage. CONCLUSION: We developed a method for the extraction of gDNA
      free of inhibitory compounds common in species of Opuntia Mill., such as pectin
      and mucilage. Compared to previously extraction protocols, our method produced
      higher yields of high-quality genomic DNA.

PMID- 29046709
TI  - Detecting spikes of wheat plants using neural networks with Laws texture energy.
AB  - BACKGROUND: The spike of a cereal plant is the grain-bearing organ whose physical
      characteristics are proxy measures of grain yield. The ability to detect and
      characterise spikes from 2D images of cereal plants, such as wheat, therefore
      provides vital information on tiller number and yield potential. RESULTS: We have
      developed a novel spike detection method for wheat plants involving, firstly, an
      improved colour index method for plant segmentation and, secondly, a neural
      network-based method using Laws texture energy for spike detection. The spike
      detection step was further improved by removing noise using an area and height
      threshold. The evaluation results showed an accuracy of over 80% in
      identification of spikes. In the proposed method we also measure the area of
      individual spikes as well as all spikes of individual plants under different
      experimental conditions. The correlation between the final average grain yield
      and spike area is also discussed in this paper. CONCLUSIONS: Our highly accurate
      yield trait phenotyping method for spike number counting and spike area
      estimation, is useful and reliable not only for grain yield estimation but also
      for detecting and quantifying subtle phenotypic variations arising from genetic
      or environmental differences.

PMID- 29046710
TI  - Pediatric falls from windows and balconies: incidents and risk factors as
      reported by newspapers in the United Arab Emirates.
AB  - BACKGROUND: Falls of children from heights (balconies and windows) usually result
      in severe injuries and death. Details on child falls from heights in the United
      Arab Emirates (UAE) are not easily accessible. Our aim was to assess the
      incidents, personal, and environmental risk factors for pediatric falls from
      windows/balconies using newspaper clippings. METHODS: We used a retrospective
      study design to electronically assess all major UAE national Arabic and English
      newspapers for reports of unintentional child falls from windows and balconies
      during 2005-2016. A structured data collection form was developed to collect
      information. Data were entered into an Excel sheet and descriptive analysis was
      performed. RESULTS: Newspaper clippings documented 96 fall incidents. After
      cleaning the data and excluding duplicate cases and intentional injuries, 81
      cases were included into the final analysis. Fifty-three percent (n = 42) were
      boys. The mean (range) age was 4.9 years (1-15). Thirty-eight (47%) children fell
      from windows and 36 (44%) from balconies. Twenty-two (27%) children climbed on
      the furniture placed on a balcony or close to a window. Twenty-five (31%)
      children were not alone in the apartment when they fell. Twenty-nine children
      fell from less than 5 floors (37%), 33 from 5 to 10 floors (42%) and 16 from more
      than 10 floors (21%). Fifteen children (19%) were hospitalized and survived the
      fall incident, while 66 died (81%). CONCLUSIONS: Newspapers proved to be useful
      to study pediatric falls from heights. It is necessary to improve window safety
      by installing window guards and raising awareness.

PMID- 29046711
TI  - Effect of methanol extract of Salviae miltiorrhizae Radix in high-fat diet
      induced hyperlipidemic mice.
AB  - BACKGROUND: The dried root of Salvia miltiorrhiza, Salviae miltiorrhizae Radix
      (SR), is one of the most popular medicinal herbs in Asian countries such as China
      and Korea. In Asian traditional medicine, SR is considered to have a bitter
      flavor, be slightly cold in nature, and exert therapeutic actions in the heart
      and liver meridians. Thus, SR has been used to control symptoms related to
      cardiovascular diseases. Hyperlipidemia is recognized as the main cause of
      cerebrovascular and heart diseases; consequently, therapeutic strategies for
      hyperlipidemia have been widely studied. In this study, the effects and molecular
      targets of methanol extract of SR (SRme) in hyperlipidemic mice were
      investigated. METHODS: High-fat diet was fed to mice to induce hyperlipidemia,
      and measurement of blood cholesterol and triglycerides were conducted to evaluate
      the effect of SRme on hyperlipidemic mice, and gene expression in mice liver was
      analyzed to identify key molecules which could be potential targets for
      developing anti-hyperlipidemic herbal medicines. RESULTS: There was no
      significant effect on the body weight gain of hyperlipidemic mice, but the
      triglyceride content in blood was significantly reduced by the administration of
      SRme to hyperlipidemic mice. Proteins such as minichromosome maintenance (Mcm)
      family which play a key role in DNA replication were identified as molecular
      targets in the amelioration of hyperlipidemia. CONCLUSIONS: SRme ameliorated
      hyperlipidemia in high-fat diet fed mice by inhibiting increase of blood serum
      level of triglycerides. And several proteins such as Mcm proteins were deduced to
      be molecular targets in treating hyperlipidemia.

PMID- 29046712
TI  - Integration of human papillomavirus 16 in esophageal carcinoma samples.
AB  - BACKGROUND: Esophageal carcinoma (EC) is one of the major cancers in China. In
      1982, Syrjanen first hypothesized the relationship between human papillomavirus
      (HPV) infection and the development of esophageal cancer. Since then, many
      reports in the field have supported this viewpoint. This study investigated the
      etiological relationship between HPV infection and the occurrence of esophageal
      carcinoma at Tangshan City of the Hebei province in China. METHODS: 189 samples
      of esophageal carcinoma patients were collected. DNA and RNA were isolated from
      samples, HPV DNA was detected by polymerase chain reaction (PCR) using My09/11
      for HPV L1, and HPV16 was determined using type-specific primer sets for HPV16
      E6. The HPV16 integration site was verified by amplification of papillomavirus
      oncogene transcripts, and HPV16 oncogene transcript products were ligated to the
      pMD-18 T vector and sequenced to confirm the physical location of HPV16
      integration. RESULTS: 168 HPV-positive samples were detected in 189 samples, and
      among them 76 specimens were HPV16 positive. Approximately 600 bp of the HPV16
      oncogene transcript were detected in nine esophageal cancer samples. Sequence
      analysis revealed that HPV16 E7 integrated into human chromosome 2 in three
      samples, into human chromosome 5 in one sample, into human chromosome 6 in one
      sample, into human chromosome 8 in two samples, and into human chromosome 17 in
      two samples. The results verified that the integrated HPV16 E7 in five samples
      harbored one mutation of viral DNA compared with the HPV16 sequence provided in
      GenBank (K02718). CONCLUSIONS: The high prevalence of HPV16 suggests that HPV16
      may play an etiological role in the development of esophageal cancer. The
      integration of HPV16 into host cell chromosomes suggests that persistent HPV
      infection is key for esophageal epithelial cell malignant transformation and
      carcinogenesis.

PMID- 29046713
TI  - HPV infection and p53 and p16 expression in esophageal cancer: are they
      prognostic factors?
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly lethal
      malignant tumor. Currently, Human papillomavirus (HPV) is suggested as a
      potential risk factor for esophageal cancer (EC) in addition to the classic risk
      factors, alcohol and tobacco, but this hypothesis still remains contradictory. We
      sought to investigate wether HPV and well-known biomarkers (p16 and p53) and
      patient-related factors that may have impact on survival of ESCC. METHODS: We
      conducted a prospective cohort study. By using multiplex PCR, we determined the
      prevalence of high risk HPV in ESCC, and evaluated the immunohistochemical
      expression of p16 and p53, molecular markers related to esophageal carcinogenesis
      in order to verify the potential influence of these variables in patients's
      survival. Survival rates were estimated using Kaplan-Meier methods. A
      multivariate confirmatory model was performed using Cox proportional hazards
      regression. RESULTS: Twelve (13.8%) of 87 patients were HPV-DNA positive.
      Positive reactions of p16 and p53 were 10.7% and 68.6%, respectively. Kaplan
      Meier analysis indicated that men (p = 0.025) had poor specific-cancer survival
      and a shorter progression-free survival (p = 0.050) as compared to women; III or
      IV clinical stage (p < 0.019) had poor specific-cancer survival and a shorter
      progression-free survival (p < 0.001) compared to I and II clinical stage; not
      submitted to surgery (<0.001) and not submitted to chemoradiotherapy (p = 0.039)
      had a poor specific-cancer survival, as well. The multivariate analysis showed
      that HPV, p16 and p53 status are not predictive parameters of progression-free
      and specific-cancer survival. CONCLUSION: HPV infection and p53 and p16
      expression are not prognostic factors in ESCC.

PMID- 29046714
TI  - Understanding the menstrual hygiene management challenges facing displaced girls
      and women: findings from qualitative assessments in Myanmar and Lebanon.
AB  - BACKGROUND: There is a significant gap in empirical evidence on the menstrual
      hygiene management (MHM) challenges faced by adolescent girls and women in
      emergency contexts, and on appropriate humanitarian response approaches to meet
      their needs in diverse emergency contexts. To begin filling the gap in the
      evidence, we conducted a study in two diverse contexts (Myanmar and Lebanon),
      exploring the MHM barriers facing girls and women, and the various relevant
      sectoral responses being conducted (e.g. water, sanitation and hygiene (WASH),
      Protection, Health, Education and Camp Management). METHODS: Two qualitative
      assessments were conducted: one in camps for internally displaced populations in
      Myanmar, and one with refugees living in informal settlements and host
      communities in Lebanon. Key informant interviews were conducted with emergency
      response staff in both sites, and focus group discussion and participatory
      mapping activities conducted with adolescent girls and women. RESULTS: Key
      findings included that there was insufficient access to safe and private
      facilities for MHM coupled with displacement induced shifts in menstrual
      practices by girls and women. Among staff, there was a narrow interpretation of
      what an MHM response includes, with a focus on supplies; significant interest in
      understanding what an improved MHM response would include and acknowledgement of
      limited existing MHM guidance across various sectors; and insufficient
      consultation with beneficiaries, related to discomfort asking about menstruation,
      and limited coordination between sectors. CONCLUSIONS: There is a significant
      need for improved guidance across all relevant sectors for improving MHM response
      in emergency context, along with increased evidence on effective approaches for
      integrating MHM into existing responses.

PMID- 29046715
TI  - Mental health training for primary health care workers and implication for
      success of integration of mental health into primary care: evaluation of effect
      on knowledge, attitude and practices (KAP).
AB  - BACKGROUND: Mental disorders are always remained a neglected public health
      problems in low and middle-income countries (LMICs), most people with mental
      disorders never receive effective care and there is a large treatment gap. In
      order to solve the problem integration of mental health into primary health care
      is recommended and in Ethiopia implementation of the scale of mental health
      services at primary health care level was started in 2014. For the success of the
      integration of mental health into primary health care, primary care health
      professionals are the key personnel who are responsible for the management of
      mental, neurologic and substance use disorders. However, proper training and
      education of primary care health professionals is mandatory for an optimal
      performance and success of integration. This interventional study was conducted
      to assess the effectiveness of mental health training course for scale up of
      mental health services at primary health care level in Ethiopia. METHODS: This
      quasi-experimental pre- and post-study design was conducted in Ethiopia from
      October to December 2016 using quantitative data collection methods. A total of
      94 primary health care professionals were included in the study. The intervention
      was conducted by psychiatry professionals using standardized World Health
      Organization (WHO) Mental Health Gap Action Programme (mhGAP) guide prepared for
      scaling up of mental health care through integration into primary health care
      (PHC) and general medical services. Pre- and post intervention assessment was
      done for knowledge, attitude and practice (KAP); and statistically analyzed. A
      paired sample t test with p values was performed to test the differences between
      the pre- and post-test. In additions mean and standard deviation of the responses
      were calculated. Overall the response rate was 100% at the end of the
      intervention. RESULTS: The study resulted in a significant improvement in
      knowledge, attitude and practice (KAP) of PHC workers about all the four mental,
      neurologic and substance use disorders during the post intervention survey (p <
      0.05). Post intervention the knowledge of health professionals increased by
      53.19% for psychosis, 42.56% for depression, 19.25% for epilepsy and 54.22% for
      alcohol use disorders. Similarly, post intervention attitude increased by 55.32%
      for psychosis, 40.42% for depression, 36.17% for epilepsy and 43.6% for alcohol
      use disorders. In addition, post intervention case identification rate increased
      by 62.78% for psychosis, 55.46% for depression, 21.35% for epilepsy and 41.49%
      for alcohol use disorders with significant p value (p < 0.05). CONCLUSIONS: The
      study results suggest that mental health training could be an effective
      intervention for improving knowledge, attitudes, and practices among primary
      health care professionals regarding mental, neurologic and substance use
      disorders. Training is a prerequisite and vital to enhance the knowledge,
      attitude, and practice of primary care professionals which plays a significant
      role for the easy success of integrated care and treatment of mental, neurologic
      and substance use disorders into the existing general health care services.

PMID- 29046716
TI  - A multi-national comparison of antipsychotic drug use in children and
      adolescents, 2005-2012.
AB  - Over the last decades, an increase in antipsychotic (AP) prescribing and a shift
      from first-generation antipsychotics (FGA) to second-generation antipsychotics
      (SGA) among youth have been reported. However, most AP prescriptions for youth
      are off-label, and there are worrying long-term safety data in youth. The
      objective of this study was to assess multinational trends in AP use among
      children and adolescents. A repeated cross-sectional design was applied to
      cohorts from varied sources from Denmark, Germany, the Netherlands, the United
      Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The
      annual prevalence of AP use was assessed, stratified by age group, sex and
      subclass (FGA/SGA). The prevalence of AP use increased from 0.78 to 1.03% in the
      Netherlands' data, from 0.26 to 0.48% in the Danish cohort, from 0.23 to 0.32% in
      the German cohort, and from 0.1 to 0.14% in the UK cohort. In the US cohort, AP
      use decreased from 0.94 to 0.79%. In the US cohort, nearly all ATP dispensings
      were for SGA, while among the European cohorts the proportion of SGA dispensings
      grew to nearly 75% of all AP dispensings. With the exception of the Netherlands,
      AP use prevalence was highest in 15-19 year-olds. So, from 2005/6 to 2012, AP use
      prevalence increased in all youth cohorts from European countries and decreased
      in the US cohort. SGA were favoured in all countries' cohorts.

PMID- 29046717
TI  - Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary
      commercial 3D printer.
AB  - BACKGROUND: The primary objective of Tissue engineering is a regeneration or
      replacement of tissues or organs damaged by disease, injury, or congenital
      anomalies. At present, Tissue engineering repairs damaged tissues and organs with
      artificial supporting structures called scaffolds. These are used for attachment
      and subsequent growth of appropriate cells. During the cell growth gradual
      biodegradation of the scaffold occurs and the final product is a new tissue with
      the desired shape and properties. In recent years, research workplaces are
      focused on developing scaffold by bio-fabrication techniques to achieve fast,
      precise and cheap automatic manufacturing of these structures. Most promising
      techniques seem to be Rapid prototyping due to its high level of precision and
      controlling. However, this technique is still to solve various issues before it
      is easily used for scaffold fabrication. In this article we tested printing of
      clinically applicable scaffolds with use of commercially available devices and
      materials. Research presented in this article is in general focused on
      "scaffolding" on a field of bone tissue replacement. RESULTS: Commercially
      available 3D printer and Polylactic acid were used to create originally designed
      and possibly suitable scaffold structures for bone tissue engineering. We tested
      printing of scaffolds with different geometrical structures. Based on the
      osteosarcoma cells proliferation experiment and mechanical testing of designed
      scaffold samples, it will be stated that it is likely not necessary to keep the
      recommended porosity of the scaffold for bone tissue replacement at about 90%,
      and it will also be clarified why this fact eliminates mechanical properties
      issue. Moreover, it is demonstrated that the size of an individual pore could be
      double the size of the recommended range between 0.2-0.35 mm without affecting
      the cell proliferation. CONCLUSION: Rapid prototyping technique based on Fused
      deposition modelling was used for the fabrication of designed scaffold
      structures. All the experiments were performed in order to show how to possibly
      solve certain limitations and issues that are currently reported by research
      workplaces on the field of scaffold bio-fabrication. These results should provide
      new valuable knowledge for further research.

PMID- 29046718
TI  - Increased lipid production by heterologous expression of AtWRI1 transcription
      factor in Nannochloropsis salina.
AB  - BACKGROUND: Genetic engineering of microalgae is necessary to produce
      economically feasible strains for biofuel production. Current efforts are focused
      on the manipulation of individual metabolic genes, but the outcomes are not
      sufficiently stable and/or efficient for large-scale production of biofuels and
      other materials. Transcription factors (TFs) are emerging as good alternatives
      for engineering of microalgae, not only to increase production of biomaterials
      but to enhance stress tolerance. Here, we investigated an AP2 type TF Wrinkled1
      in Arabidopsis (AtWRI1) known as a key regulator of lipid biosynthesis in plants,
      and applied it to industrial microalgae, Nannochloropsis salina. RESULTS: We
      expressed AtWRI1 TF heterologously in N. salina, named NsAtWRI1, in an effort to
      re-enact its key regulatory function of lipid accumulation. Stable integration
      AtWRI1 was confirmed by RESDA PCR, and its expression was confirmed by Western
      blotting using the FLAG tag. Characterizations of transformants revealed that the
      neutral and total lipid contents were greater in NsAtWRI1 transformants than in
      WT under both normal and stress conditions from day 8. Especially, total lipid
      contents were 36.5 and 44.7% higher in NsAtWRI1 2-3 than in WT under normal and
      osmotic stress condition, respectively. FAME contents of NsAtWRI1 2-3 were also
      increased compared to WT. As a result, FAME yield of NsAtWRI1 2-3 was increased
      to 768 mg/L/day, which was 64% higher than that of WT under the normal condition.
      We identified candidates of AtWRI1-regulated genes by searching for the presence
      of the AW-box in promoter regions, among which lipid metabolic genes were further
      analyzed by qRT-PCR. Overall, qRT-PCR results on day 1 indicated that AtWRI1 down
      regulated TAGL and DAGK, and up-regulated PPDK, LPL, LPGAT1, and PDH, resulting
      in enhanced lipid production in NsAtWRI1 transformants from early growth phase.
      CONCLUSION: AtWRI1 TF regulated several genes involved in lipid synthesis in N.
      salina, resulting in enhancement of neutral lipid and FAME production. These
      findings suggest that heterologous expression of AtWRI1 TF can be utilized for
      efficient biofuel production in industrial microalgae.

PMID- 29046719
TI  - Conversion of cellulose and hemicellulose of biomass simultaneously to acetoin by
      thermophilic simultaneous saccharification and fermentation.
AB  - BACKGROUND: Acetoin (3-hydroxy-2-butanone), the precursor of biofuel 2,3
      butanediol, is an important bio-based platform chemical with wide applications.
      Fermenting the low-cost and renewable plant biomass is undoubtedly a promising
      strategy for acetoin production. Isothermal simultaneous saccharification and
      fermentation (SSF) is regarded as an efficient method for bioconversion of
      lignocellulosic biomass, in which the temperature optima fitting for both
      lignocellulose-degrading enzymes and microbial strains. RESULTS: A thermotolerant
      (up to 52  degrees C) acetoin producer Bacillus subtilis IPE5-4 which
      simultaneously consumed glucose and xylose was isolated and identified. By
      compound mutagenesis, the mutant IPE5-4-UD-4 with higher acetoin productivity was
      selected. When fermenting at 50  degrees C in a 5-L bioreactor using glucose as
      the feedstock by strain IPE5-4-UD-4, the acetoin concentration reached 28.83 +/-
      0.91 g L-1 with the acetoin yield and productivity of 0.34 g g-1 glucose and 0.60
      g L-1 h-1, respectively. Furthermore, an optimized and thermophilic SSF process
      operating at 50  degrees C was conducted for acetoin production from alkali
      pretreated corncob (APC). An acetoin concentration of 12.55 +/- 0.28 g L-1 was
      achieved by strain IPE5-4-UD-4 in shake flask SSF, with the acetoin yield and
      productivity of 0.25 g g-1 APC and 0.17 g L-1 h-1. Meanwhile, the utilization of
      cellulose and hemicellulose in the SSF approach reached 96.34 and 93.29%,
      respectively. When further fermented at 50  degrees C in a 5-L bioreactor, the
      concentration of acetoin reached the maximum of 22.76 +/- 1.16 g L-1, with the
      acetoin yield and productivity reaching, respectively, 0.46 g g-1 APC and 0.38 g
      L-1 h-1. This was by far the highest acetoin yield in SSF from lignocellulosic
      biomass. CONCLUSIONS: This thermophilic SSF process provided an efficient and
      economical route for acetoin production from lignocellulosic biomass at ideal
      temperature for both enzymatic hydrolysis and microbial fermentation.

PMID- 29046720
TI  - A new method to evaluate temperature vs. pH activity profiles for
      biotechnological relevant enzymes.
AB  - BACKGROUND: Glycoside hydrolases are important for various industrial and
      scientific applications. Determination of their temperature as well as pH optima
      and range is crucial to evaluate whether an enzyme is suitable for application in
      a biotechnological process. These basic characteristics of enzymes are generally
      determined by two separate measurements. However, these lead to a two-dimensional
      assessment of the pH range at one temperature (and vice versa) and do not allow
      prediction of the relative enzymatic performance at any pH/temperature
      combination of interest. In this work, we demonstrate a new method that is based
      on experimental data and visualizes the relationship among pH, temperature, and
      activity at a glance in a three-dimensional contour plot. RESULTS: In this study,
      we present a method to determine the relative activity of an enzyme at 96
      different combinations of pH and temperature in parallel. For this purpose, we
      used a gradient PCR cycler and a citrate-phosphate-based buffer system in
      microtiter plates. The approach was successfully tested with various substrates
      and diverse assays for glycoside hydrolases. Furthermore, its applicability was
      demonstrated for single enzymes using the endoglucanase Cel8A from Clostridium
      thermocellum as well as the commercially available complex enzyme mixture
      Celluclast(r). Thereby, we developed a fast and adaptable method to determine
      simultaneously both pH and temperature ranges of enzymes over a wide range of
      conditions, an easy transformation of the experimental data into a contour plot
      for visualization, and the necessary controls. With our method, the suitability
      of an enzyme or enzyme mixture for any chosen combination of temperature and pH
      can easily be assessed at a glance. CONCLUSIONS: We propose a method that offers
      significant advantages over commonly used methods to determine the pH and
      temperature ranges of enzymes. The overall relationship among pH, temperature,
      and activity is visualized. Our method could be applied to evaluate exactly what
      conditions have to be met for optimal utilization of an enzyme or enzyme mixture
      for both lab-scale and industrial processes. Adaptation to other enzymes,
      including proteases, should be possible and the method may also lead to a
      platform for additional applications, such as inactivation kinetics analysis.

PMID- 29046721
TI  - Engineering Bacillus licheniformis as a thermophilic platform for the production
      of l-lactic acid from lignocellulose-derived sugars.
AB  - BACKGROUND: Bacillus licheniformis MW3 as a GRAS and thermophilic strain is a
      promising microorganism for chemical and biofuel production. However, its
      capacity to co-utilize glucose and xylose, the major sugars found in
      lignocellulosic biomass, is severely impaired by glucose-mediated carbon
      catabolite repression (CCR). In this study, a "dual-channel" process was
      implemented to engineer strain MW3 for simultaneous utilization of glucose and
      xylose, using l-lactic acid as a target product. RESULTS: A non
      phosphotransferase system (PTS) glucose uptake route was activated via deletion
      of the glucose transporter gene ptsG and introduction of the galactose permease
      gene galP. After replacing the promoter of glucokinase gene glck with the strong
      promoter Pals, the engineered strain recovered glucose consumption and utilized
      glucose and xylose simultaneously. Meanwhile, to improve the consumption rate of
      xylose in this strain, several measures were undertaken, such as relieving the
      regulation of the xylose repressor XylR, reducing the catabolite-responsive
      element, and optimizing the rate-limiting step. Knockout of ethanol and acetic
      acid pathway genes further increased lactic acid yield by 6.2%. The resultant
      strain, RH15, was capable of producing 121.9 g/L l-lactic acid at high yield
      (95.3%) after 40 h of fermentation from a mixture of glucose and xylose. When a
      lignocellulosic hydrolysate was used as the substrate, 99.3 g/L l-lactic acid was
      produced within 40 h, with a specific productivity of 2.48 g/[L h] and a yield of
      94.6%. CONCLUSIONS: Our engineered strain B. licheniformis RH15 could
      thermophilically produced l-lactic acid from lignocellulosic hydrolysate with
      relatively high concentration and productivity at levels that were competitive
      with most reported cases of l-lactic acid-producers. Thus, the engineered strain
      might be used as a platform for the production of other chemicals. In addition to
      engineering the B. licheniformis strain, the "dual-channel" process might serve
      as an alternative method for engineering a variety of other strains.

PMID- 29046722
TI  - Replacing process water and nitrogen sources with biogas slurry during cellulosic
      ethanol production.
AB  - BACKGROUND: Environmental issues, such as the fossil energy crisis, have resulted
      in increased public attention to use bioethanol as an alternative renewable
      energy. For ethanol production, water and nutrient consumption has become
      increasingly important factors being considered by the bioethanol industry as
      reducing the consumption of these resources would decrease the overall cost of
      ethanol production. Biogas slurry contains not only large amounts of wastewater,
      but also the nutrients required for microbial growth, e.g., nitrogen, ammonia,
      phosphate, and potassium. Therefore, biogas slurry is an attractive potential
      resource for bioethanol production that could serve as an alternative to process
      water and nitrogen sources. RESULTS: In this study, we propose a method that
      replaces the process water and nitrogen sources needed for cellulosic ethanol
      production by Zymomonas mobilis with biogas slurry. To test the efficacy of these
      methods, corn straw degradation following pretreatment with diluted NaOH and
      enzymatic hydrolysis in the absence of fresh water was evaluated. Then, ethanol
      fermentation using the ethanologenic bacterial strain Z. mobilis ZMT2 was
      conducted without supplementing with additional nitrogen sources. After
      pretreatment with 1.34% NaOH (w/v) diluted in 100% biogas slurry and continuous
      enzymatic hydrolysis for 144 h, 29.19 g/L glucose and 12.76 g/L xylose were
      generated from 30 g dry corn straw. The maximum ethanol concentration acquired
      was 13.75 g/L, which was a yield of 72.63% ethanol from the hydrolysate medium.
      Nearly 94.87% of the ammonia nitrogen was depleted and no nitrate nitrogen
      remained after ethanol fermentation. The use of biogas slurry as an alternative
      to process water and nitrogen sources may decrease the cost of cellulosic ethanol
      production by 10.0-20.0%. By combining pretreatment with NaOH diluted in biogas
      slurry, enzymatic hydrolysis, and ethanol fermentation, 56.3 kg of ethanol was
      produced by Z. mobilis ZMT-2 through fermentation of 1000 kg of dried corn straw.
      CONCLUSIONS: In this study, biogas slurry replaced process water and nitrogen
      sources during cellulosic ethanol production. The results suggest that biogas
      slurry is a potential alternative to water when pretreating corn straw and, thus,
      has important potential applications in cellulosic ethanol production from corn
      straw. This study not only provides a novel method for utilizing biogas slurry,
      but also demonstrates a means of reducing the overall cost of cellulosic ethanol.

PMID- 29046723
TI  - Etiological factors in hallux valgus, a three-dimensional analysis of the first
      metatarsal.
AB  - BACKGROUND: It has been reported that hallux valgus (HV) is associated with axial
      rotation of the first metatarsal (1MT). However, the association between HV and
      torsion of the 1MT head with respect to the base has not been previously
      investigated. The present study examined whether there was a significant
      difference in 1MT torsion between HV and control groups. METHODS: Three
      dimensional (3D) computed tomography (CT) scans of 39 ft were obtained, and 3D
      surface models of the 1MT were generated to quantify the torsion of the head with
      respect to the base. The HV group consisted of 27 ft from 27 women (69.5 +/- 7.5
      years old). Only the feet of HV patients with an HV angle >20 degrees  on weight
      bearing radiography were selected for analysis. The control group consisted of 12
      ft from 12 women (67.7 +/- 7.2 years old). In a virtual 3D space, two unit
      vectors, which describe the orientation of the 1MT head and base, were
      calculated. The angle formed by these two unit vectors representing 1MT torsion
      was compared between the control and hallux valgus groups. RESULTS: The mean (+/-
      standard deviation) of the torsional angle of the 1MT was 17.6 (+/- 7.7) degrees 
      and 4.7 (+/- 4.0) degrees  in the HV and control groups, respectively, and the
      difference was significant (p < 0.01). CONCLUSIONS: This is the first study, to
      the best of our knowledge, to investigate 1MT torsion in HV patients using CT
      based 3D analysis. The 1MT showed significant eversion in hallux valgus patients
      compared to control group patients.

PMID- 29046724
TI  - The integration of a Podiatrist into an orthopaedic department: a cost
      consequences analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the cost-consequences of a
      podiatry-led triage clinic provided in an orthopaedic department relative to
      usual care for non-urgent foot and ankle complaints in an Australian tertiary
      care hospital. METHODS: All new, non-urgent foot and ankle patients seen in an
      outpatient orthopaedic department were included in this study. The patients seen
      between 2014 and 2015 by Orthopaedic Surgeons were considered 'usual care', the
      patients seen between 2015 and 2016 by a Podiatrist were considered the 'Podiatry
      Triage Clinic'. Data on new and review patient appointments; the number of new
      patients / session; the number of appointments / patient; the number of patients
      discharged; the surgical conversion rate; staff time; and imaging use were
      collected. A cost-consequences analysis, undertaken from a healthcare provider
      perspective (hospital) estimated the incremental resource use, costs and effects
      of the Podiatry Triage Clinic relative to usual care over a 12-month period.
      RESULTS: The Orthopaedic Surgeons and Podiatrist consulted with 72 and 212 new
      patients during the usual care and triage periods, respectively. The Podiatrist
      consulted with more new patients / session, mean (SD) of 3.6 (1.0) versus 0.7
      (0.8), p < 0.001 and utilised less appointments / patient than the Orthopaedic
      Surgeons, mean (SD) of 1.3 (0.6) versus 1.9 (1.1), p < 0.001. The percentage of
      patients discharged without surgery was similar in the Podiatry Triage Clinic and
      usual care, 80.3% and 87.5% p = 0.135, respectively, but the surgical conversion
      rate was higher in the Podiatry Triage Clinic, 76.1% versus 12.5% p < 0.001. The
      total integrated appointment cost for the 12-month usual care period was $32,744,
      which represented a cost of $454.78 / patient. The total appointment and imaging
      cost during the triage period was $19,999, representing $94.34 / patient. Further
      analysis, suggests that the projected annual saving of integrating a Podiatry
      Triage Clinic versus an orthopaedic clinic alone is $50,441. CONCLUSIONS: The
      integration of a Podiatrist into an orthopaedic department significantly
      increases the number of patients seen, is cost-effective, improves the surgical
      conversion rate and improves the utilisation of Orthopaedic Surgeons.

PMID- 29046725
TI  - Clinical photographic observation of plantar corns and callus associated with a
      nominal scale classification and inter- observer reliability study in a student
      population.
AB  - BACKGROUND: The management of plantar corns and callus has a low cost-benefit
      with reduced prioritisation in healthcare. The distinction between types of
      keratin lesions that forms corns and callus has attracted limited interest.
      Observation is imperative to improving diagnostic predictions and a number of
      studies point to some confusion as to how best to achieve this. The use of
      photographic observation has been proposed to improve our understanding of
      intractable keratin lesions. METHODS: Students from a podiatry school reviewed
      photographs where plantar keratin lesions were divided into four nominal groups;
      light callus (Grade 1), heavy defined callus (Grade 2), concentric keratin plugs
      (Grade 3) and callus with deeper density changes under the forefoot (Grade 4). A
      group of 'experts' assigned from qualified podiatrists validated the observer
      rated responses by the students. RESULTS: Cohen's weighted statistic (k) was used
      to measure inter-observer reliability. First year students (unskilled) performed
      less well when viewing photographs (k = 0.33) compared to third year students
      (semi-skilled, k = 0.62). The experts performed better than students (k = 0.88)
      providing consistency with wound care models in other studies. CONCLUSIONS:
      Improved clinical annotation of clinical features, supported by classification of
      keratin- based lesions, combined with patient outcome tools, could improve the
      scientific rationale to prioritise patient care. Problems associated with
      photographic assessment involves trying to differentiate similar lesions without
      the benefit of direct palpation. Direct observation of callus with and without
      debridement requires further investigation alongside the model proposed in this
      paper.

PMID- 29046726
TI  - Helicobacter pylori virulence genes of minor ethnic groups in North Thailand.
AB  - BACKGROUND: There are few studies analyzed concurrently the prevalence and
      genotypes of Helicobacter pylori infection with the ancestor origins from
      different ethnics, especially with including minority groups. We recruited a
      total of 289 patients in MaeSot, Thailand (154 Thai, 14 Thai-Chinese, 29 Karen
      and 92 Hmong ethnics). The virulence genes and genealogy of the strains were
      determined by PCR-based sequencing. RESULTS: Based on culture and
      histology/immunohistochemistry, the prevalence of H. pylori infection was 54.5%
      (158/289). Among 152 isolates cultured, the East-Asian-type cagA was predominant
      genotype among strains from Hmong, Thai-Chinese and Thai (96.0% [48/50], 85.7%
      [6/7] and 62.7% [47/75], respectively), whilst majority of strains from Karen had
      Western-type cagA (73.3% [11/15]). Patients infected with the East-Asian-type
      cagA strains had significantly higher activity and intestinal metaplasia in the
      antrum and activity in the corpus than those with Western-type cagA (P = 0.024,
      0.006 and 0.005, respectively). The multilocus sequencing typing analysis
      discriminated that most strains from Hmong and Thai-Chinese belonged to hspEAsia
      (92.0 and 85.7%, respectively), whereas strains from Karen predominantly
      possessed hpAsia2 (86.7%) and strains from Thai were classified into hspEAsia
      (45.2%) and hpAsia2 (31.1%). CONCLUSIONS: Helicobacter pylori genotypes were
      relatively different among ethnic groups in Thailand and were associated with the
      source of ancestor even living in a small rural town. Caution and careful check
      up are required especially on Hmong ethnic associated with high prevalence of
      virulence genotypes of H. pylori.

PMID- 29046727
TI  - Elevated circulating fasting glucagon-like peptide-1 in surgical patients with
      aortic valve disease and diabetes.
AB  - BACKGROUND: Diabetes is a risk factor for peripheral, coronary, and
      cerebrovascular disease. In contrast, results also indicate that patients with
      diabetes have reduced prevalence of aortic aneurysms, although the mechanisms
      remain largely unknown. We hypothesize that altered endogenous secretion of the
      intestinal hormone glucagon-like peptide-1 (GLP-1)-previously shown to protect
      from aneurysm formation, and governing many of the mechanisms thought to be
      involved in aneurysm formation-may provide insights into the mechanisms
      underlying the inverse relationship of diabetes and aneurysm. METHODS: We
      undertook a case-control study to characterize circulating plasma GLP-1 levels in
      diabetic and non-diabetic surgical patients with aortic valve disease, and with
      or without ascending aortic dilation. The cohort included patients with a
      bicuspid aortic valve (BAV), a common congenital disorder associated with
      ascending aortic aneurysm, as well as patients with a tricuspid aortic valve
      (TAV). RESULTS: In our patient group, diabetes was characterized by a significant
      increase in fasting plasma GLP-1 levels. Further, we show that aortic dilation in
      these patients was associated with a significant increase in fasting plasma GLP
      1, although a significant increase in the intact and bioactive peptide could not
      be detected in BAV patients with aortic dilation. CONCLUSION: A subgroup of
      diabetic patients with aortic valve pathology have increased fasting plasma GLP-1
      levels, which may be of importance for the low prevalence of aortic dilation in
      this patient group. Further, in TAV patients, GLP-1 secretion and plasma levels
      of intact GLP-1 are upregulated in association with aortic dilation, possibly
      indicating a compensatory mechanism.

PMID- 29046728
TI  - High prevalence of Berardinelli-Seip Congenital Lipodystrophy in Rio Grande do
      Norte State, Northeast Brazil.
AB  - BACKGROUND: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare disease
      characterized by the almost complete absence of adipose tissue. Although a large
      number of BSCL cases was previously identified in Rio Grande do Norte (RN), a
      state in Northeast Brazil, its prevalence in RN regions and municipalities
      remains unknown. The purpose of this study was to better characterize the
      prevalence of BSCL in RN. METHODS: A descriptive study was conducted using
      secondary data obtained from the Association of Parents and People with BSCL of
      RN to determine its prevalence. The patients' socio-demographic characteristics
      and geolocalization were analyzed. RESULTS: We estimated a total of 103 BSCL
      cases in RN, resulting in a prevalence of 3.23 per 100,000 people. The Central
      Potiguar mesoregion, Serido territory, Carnauba dos Dantas and Timbauba dos
      Batistas municipalities had a much higher prevalence of BSCL, with 20.56, 20.66,
      498.05 and 217.85 per 100,000 people, respectively. CONCLUSIONS: Together, our
      results showed that BSCL is highly prevalent in RN and confirmed that our state
      has one of the highest prevalences of this lipodystrophy worldwide. More studies
      are still needed to better estimate the prevalence and incidence of BSCL in RN as
      well as in other states in Brazil. Trial registration Study Number
      31809314.0.0000.5568.

PMID- 29046729
TI  - Long-term feeding of high-fat plus high-fructose diet induces isolated impaired
      glucose tolerance and skeletal muscle insulin resistance in miniature pigs.
AB  - BACKGROUND: During the prediabetic development, the changes in beta-cell function
      and tissue-specific insulin resistance have been described. However, there are
      conflicting views in insulin secretory capacity between early clinical
      observation and recent proposed mathematical model. On the basis of digestive and
      metabolic similarities with humans, swine have great potential as an animal model
      to investigate the progressive mechanisms of prediabetes. The aim of this study
      was to investigate the insulin secretory response and tissue-specific insulin
      resistance in a dietary-induced prediabetic porcine model. METHODS: Adult male
      Taiwan Lee-Sung miniature pigs were randomized into two groups: (1) low-fat diet
      and (2) high-fat plus high-fructose diet (HFHF; 20.9% crude fat and 17.8%
      fructose). During the 12-month dietary intervention, body weights and blood
      glucose levels were measured monthly. Intravenous glucose tolerance test was used
      for measuring glucose tolerance and insulin secretory capacity. At the end of the
      experiment, liver and soleus muscle specimens were collected for ex vivo insulin
      sensitivity testing. RESULTS: The results showed that the HFHF group had obesity,
      hyperinsulinemia, and dyslipidemia, but normal fasting glucose levels. The HFHF
      pigs exhibited enhanced first- and second-phase insulin secretion and high 2-h
      postload glucose levels in intravenous glucose tolerance test. Furthermore, the
      skeletal muscle specimens from the HFHF group were desensitized to insulin
      stimulation as shown by the lack of AKT Ser473 phosphorylation; however, the
      liver specimens remained a normal response. CONCLUSIONS: In conclusion, the HFHF
      diet-fed pigs developed isolated impaired glucose tolerance corresponding to
      prediabetes with an intense insulin secretory response and skeletal muscle
      insulin resistance.

PMID- 29046730
TI  - Aliskiren effect on non-alcoholic steatohepatitis in metabolic syndrome.
AB  - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is highly associated with
      metabolic syndrome, a major cause of morbidity in the globalized society. The
      renin-angiotensin system (RAS) influences hepatic fatty acid metabolism,
      inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the
      effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related
      NASH. METHODS: C57BL/6 male mice (n = 45) were divided into three groups:
      controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days
      and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for
      5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for
      the final 2 weeks. Glycemic and insulin levels, hepatic lipid profile,
      histological parameters and inflammatory protein expression were analyzed.
      RESULTS: Aliskiren normalized plasma glucose and insulin levels, reduced
      cholesterol, triglycerides and total fat accumulation in liver and diminished
      hepatic injury, steatosis and fibrosis. These results could be explained by the
      ability of aliskiren to block angiotensin-II, lowering oxidative stress and
      inflammation in liver. Also, it exhibited a beneficial effect in increasing
      insulin sensitivity. CONCLUSION: These findings support the use of aliskiren in
      the treatment of metabolic syndrome underlying conditions. However, clinical
      studies are indispensable to test its effectiveness in the treatment of patients
      with metabolic syndrome.

PMID- 29046731
TI  - Promoter methylation inhibits expression of tumor suppressor KIBRA in human clear
      cell renal cell carcinoma.
AB  - BACKGROUND: KIBRA has been suggested as a key regulator of the Hippo signaling
      pathway, regulating organ size, cell contact inhibition, tissue regeneration as
      well as tumorigenesis and cystogenesis. We recently reported that human KIBRA
      expression depends on a complex alternative CpG-rich promoter system. Our current
      study aimed at the identification of epigenetic mechanisms associated with
      alterations in KIBRA expression regulation. RESULTS: We identified two separated
      methylation-sensitive CpG islands located to independent KIBRA promoter regions.
      In vitro promoter methylation analysis using human neuroblastoma (SH-SY5Y) and
      immortalized kidney cells (IHKE) revealed that total promoter methylation by CpG
      methyltransferase SssI resulted in complete abrogation of transcriptional
      activity (p < 0.001), while partial methylation by HpaII selectively repressed
      KIBRA core promoter activity in kidney cells (p < 0.001). Cell culture-based
      experiments demonstrated that 5-azacitidine may be used to restore KIBRA mRNA and
      protein levels, while overexpression of transcription factor SP1 also induced
      KIBRA upregulation (all p < 0.001). Furthermore, SP1 transactivation of KIBRA
      transcription was largely prevented by methylation of KIBRA regulatory elements
      (p < 0.001). Analysis of human kidney biopsies revealed that KIBRA promoter
      methylation was associated with human clear cell renal cell carcinoma (ccRCC; n =
      8 vs 16 controls, OR = 1.921, [CI 95% = 1.369-2.695]). The subsequent
      determination of KIBRA mRNA levels by real-time PCR in a larger patient sample
      confirmed significantly reduced KIBRA expression in ccRCC (n = 32) compared to
      non-neoplastic human kidney tissue samples (controls, n = 32, p < 0.001).
      CONCLUSION: We conclude that epigenetic downregulation of tumor suppressor KIBRA
      may involve impaired SP1 binding to functional methylation-sensitive KIBRA
      promoter elements as observed in human kidney clear cell carcinoma. Our findings
      provide a pathophysiological basis for future studies on altered KIBRA regulation
      in clinical disease entities such as renal cancer.

PMID- 29046733
TI  - Mosaic genome-wide maternal isodiploidy: an extreme form of imprinting disorder
      presenting as prenatal diagnostic challenge.
AB  - BACKGROUND: Uniparental disomy of certain chromosomes are associated with a group
      of well-known genetic syndromes referred to as imprinting disorders. However, the
      extreme form of uniparental disomy affecting the whole genome is usually not
      compatible with life, with the exception of very rare cases of patients with
      mosaic genome-wide uniparental disomy reported in the literature. RESULTS: We
      here report on a fetus with intrauterine growth retardation and malformations
      observed on prenatal ultrasound leading to invasive prenatal testing. By
      cytogenetic (conventional karyotyping), molecular cytogenetic (QF-PCR, FISH,
      array), and methylation (MS-MLPA) analyses of amniotic fluid, we detected
      mosaicism for one cell line with genome-wide maternal uniparental disomy and a
      second diploid cell line of biparental inheritance with trisomy X due to paternal
      isodisomy X. As expected for this constellation, we observed DNA methylation
      changes at all imprinted loci investigated. CONCLUSIONS: This report adds new
      information on phenotypic outcome of mosaic genome-wide maternal uniparental
      disomy leading to an extreme form of multilocus imprinting disturbance. Moreover,
      the findings highlight the technical challenges of detecting these rare
      chromosome disorders prenatally.

PMID- 29046732
TI  - Effect of a diet containing folate and hazelnut oil capsule on the methylation
      level of the ADRB3 gene, lipid profile and oxidative stress in overweight or
      obese women.
AB  - BACKGROUND: Studies of genes that play an important role in the development of
      obesity are needed, especially studies focusing on genes that regulate food
      intake and affect nutrient metabolism. For example, the beta-3 adrenergic
      receptor (ADRB3) responds to noradrenaline and mediates lipolysis in adipocytes.
      METHODS: This was a controlled intervention study involving 40 overweight and
      obese adult women in which food intake, anthropometric measurements, biochemical
      analyses, and methylation levels of the ADRB3 gene were evaluated before and
      after intervention. The individuals were randomized into four groups: group 1
      (G1) received 300 g of vegetables and legumes containing on average 191 MUg/day
      of folate and 1 hazelnut oil capsule; group 2 (G2) received 300 g of vegetables
      and legumes containing on average 191 MUg/day of folate and 1 placebo capsule;
      group 3 (G3) received 300 g of vegetables and legumes containing on average 90
      MUg/day of folate and 1 hazelnut oil capsule; and individuals in group 4 (G4)
      were only followed-up and maintained their regular dietary habits. Statistical
      analysis was performed using analysis of variance (ANOVA), Student's t test and
      simple regression, using STATA 13 software. RESULTS: In the total sample, after
      the intervention, the women classified as overweight and obese did not present
      weight loss, and there was a reduction in the methylation levels of the ADRB3
      gene and malondialdehyde, as well as an increase in high-density lipoprotein
      cholesterol and total antioxidant capacity. CONCLUSIONS: The beneficial effect of
      the intake of a hazelnut capsule on the methylation levels of the ADRB3 gene was
      demonstrated for the first time. TRIAL REGISTRATION: ClinicalTrials.gov, NCT
      02846025.

PMID- 29046735
TI  - Identification of a key role of widespread epigenetic drift in Barrett's
      esophagus and esophageal adenocarcinoma.
AB  - BACKGROUND: Recent studies have identified age-related changes in DNA methylation
      patterns in normal and cancer tissues in a process that is called epigenetic
      drift. However, the evolving patterns, functional consequences, and dynamics of
      epigenetic drift during carcinogenesis remain largely unexplored. Here we analyze
      the evolution of epigenetic drift patterns during progression from normal
      squamous esophagus tissue to Barrett's esophagus (BE) to esophageal
      adenocarcinoma (EAC) using 173 tissue samples from 100 (nonfamilial) BE patients,
      along with publically available datasets including The Cancer Genome Atlas
      (TCGA). RESULTS: Our analysis reveals extensive methylomic drift between normal
      squamous esophagus and BE tissues in nonprogressed BE patients, with differential
      drift affecting 4024 (24%) of 16,984 normally hypomethylated cytosine-guanine
      dinucleotides (CpGs) occurring in CpG islands. The majority (63%) of islands that
      include drift CpGs are associated with gene promoter regions. Island CpGs that
      drift have stronger pairwise correlations than static islands, reflecting
      collective drift consistent with processive DNA methylation maintenance.
      Individual BE tissues are extremely heterogeneous in their distribution of
      methylomic drift and encompass unimodal low-drift to bimodal high-drift patterns,
      reflective of differences in BE tissue age. Further analysis of longitudinally
      collected biopsy samples from 20 BE patients confirm the time-dependent evolution
      of these drift patterns. Drift patterns in EAC are similar to those in BE, but
      frequently exhibit enhanced bimodality and advanced mode drift. To better
      understand the observed drift patterns, we developed a multicellular stochastic
      model at the CpG island level. Importantly, we find that nonlinear feedback in
      the model between mean island methylation and CpG methylation rates is able to
      explain the widely heterogeneous collective drift patterns. Using matched gene
      expression and DNA methylation data in EAC from TCGA and other publically
      available data, we also find that advanced methylomic drift is correlated with
      significant transcriptional repression of ~ 200 genes in important regulatory and
      developmental pathways, including several checkpoint and tumor suppressor-like
      genes. CONCLUSIONS: Taken together, our findings suggest that epigenetic drift
      evolution acts to significantly reduce the expression of developmental genes that
      may alter tissue characteristics and improve functional adaptation during BE to
      EAC progression.

PMID- 29046737
TI  - Between the West and Asia: "Humanistic" Japanese Family Planning in the Cold War.
AB  - This paper studies the formation of Japanese ventures in family planning deployed
      in various villages in Asia from the 1960s onward in the name of development aid.
      By critically examining how Asia became the priority area for Japan's
      international cooperation in family planning and by analyzing how the adjective
      "humanistic" was used to underscore the originality of Japan's family planning
      program overseas, the paper shows that visions of Japanese actors were directly
      informed by Japan's delicate position in Cold War geopolitics, between the
      imagined West represented by the United States and "underdeveloped" Asia, at a
      time when Japan was striving to (re-)establish its position in world politics and
      economics. Additionally, by highlighting subjectivities and intra-Asian networks
      centered on Japanese actors, the paper also aims to destabilize the current
      historiography on population control which has hitherto focused either on Western
      actors in the transnational population control movement or on non-Western
      "acceptors" subjected to the population control programs.

PMID- 29046736
TI  - Factors determining dry deposition of total mercury and organic carbon in house
      dust of residents of the Tri-city and the surrounding area (Baltic Sea coast).
AB  - The purpose of this study was to find out what factors determine the deposition
      levels of mercury and organic carbon in household dust in the Tri-city region
      (southern Baltic Sea coast). Analyses were performed on samples collected over
      the period of 2 years, from 2013 to 2015, always in the heating season. The
      deposition of organic carbon was between 4and 210 mg m-2 month-1, while mercury
      deposition ranged from 4 to 1336 ng m-2 month-1. Deposition of mercury in
      household dust during the heating season was three times lower and deposition of
      organic carbon one and a half times lower than outdoor deposition obtained in the
      Baltic Sea region by other researchers. In the non-heating period, deposition of
      mercury in household dust was similar to outdoor deposition while deposition of
      OC was one and a half times higher. Both of the analyzed dust components reached
      higher deposition in rural areas than in cities, and both mercury and organic
      carbon were found to have higher deposition in single-family houses than in
      buildings housing several families. The increased level of OC was conditioned by
      the vicinity of the building to a road or street with a high level of traffic,
      and dust collected on the ground floor had higher Hg depositions. The presence of
      plants and pets, as well as smoking more than ten cigarettes per day, resulted in
      higher depositions of both the compounds present in household dust within the Tri
      city region.

PMID- 29046734
TI  - Epigenome-wide association study of asthma and wheeze in childhood and
      adolescence.
AB  - BACKGROUND: Asthma heritability has only been partially explained by genetic
      variants and is known to be sensitive to environmental factors, implicating
      epigenetic modifications such as DNA methylation in its pathogenesis. METHODS:
      Using data collected in the Avon Longitudinal Study of Parents and Children
      (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at
      7.5 and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of
      approx. 1000 participants. We used Mendelian randomization (MR), a method of
      causal inference that uses genetic variants as instrumental variables, to infer
      the direction of association between DNA methylation and asthma. RESULTS: We
      identified 302 CpGs associated with current asthma status (FDR-adjusted P value <
      0.05) and 445 with current wheeze status at 7.5 years, with substantial overlap
      between the two. Genes annotated to the 302 associated CpGs were enriched for
      pathways related to movement of cellular/subcellular components, locomotion,
      interleukin-4 production and eosinophil migration. All associations attenuated
      when adjusted for eosinophil and neutrophil cell count estimates. At 16.5 years,
      two sites were associated with current asthma after adjustment for cell counts.
      The CpGs mapped to the AP2A2 and IL5RA genes, with a - 2.32 [95% CI - 1.47, -
      3.18] and - 2.49 [95% CI - 1.56, - 3.43] difference in percentage methylation in
      asthma cases respectively. Two-sample bi-directional MR indicated a causal effect
      of asthma on DNA methylation at several CpG sites at 7.5 years. However,
      associations did not persist after adjustment for multiple testing. There was no
      evidence of a causal effect of asthma on DNA methylation at either of the two CpG
      sites at 16.5 years. CONCLUSION: The majority of observed associations are driven
      by higher eosinophil cell counts in asthma cases, acting as an intermediate
      phenotype, with important implications for future studies of DNA methylation in
      atopic diseases.

PMID- 29046739
TI  - High-quality-draft genomic sequence of Paenibacillus ferrarius CY1T with the
      potential to bioremediate Cd, Cr and Se contamination.
AB  - Paenibacillus ferrarius CY1T (= KCTC 33419T = CCTCC AB2013369T) is a Gram
      positive, aerobic, endospore-forming, motile and rod-shaped bacterium isolated
      from iron mineral soil. This bacterium reduces sulfate (SO42-) to S2-, which
      reacts with Cd(II) to generate precipitated CdS. It also reduces the toxic
      chromate [Cr(VI)] and selenite [Se(VI)] to the less bioavailable chromite
      [Cr(III)] and selenium (Se0), respectively. Thus, strain CY1T has the potential
      to bioremediate Cd, Cr and Se contamination, which is the main reason for the
      interest in sequencing its genome. Here we describe the features of strain CY1T,
      together with the draft genome sequence and its annotation. The 9,184,169 bp long
      genome exhibits a G + C content of 45.6%, 7909 protein-coding genes and 81 RNA
      genes. Nine putative Se(IV)-reducing genes, five putative Cr(VI) reductase and
      nine putative sulfate-reducing genes were identified in the genome.

PMID- 29046738
TI  - Colorectal cancer incidence in path_MLH1 carriers subjected to different follow
      up protocols: a Prospective Lynch Syndrome Database report.
AB  - BACKGROUND: We have previously reported a high incidence of colorectal cancer
      (CRC) in carriers of pathogenic MLH1 variants (path_MLH1) despite follow-up with
      colonoscopy including polypectomy. METHODS: The cohort included Finnish carriers
      enrolled in 3-yearly colonoscopy (n = 505; 4625 observation years) and carriers
      from other countries enrolled in colonoscopy 2-yearly or more frequently (n =
      439; 3299 observation years). We examined whether the longer interval between
      colonoscopies in Finland could explain the high incidence of CRC and whether
      disease expression correlated with differences in population CRC incidence.
      RESULTS: Cumulative CRC incidences in carriers of path_MLH1 at 70-years of age
      were 41% for males and 36% for females in the Finnish series and 58% and 55% in
      the non-Finnish series, respectively (p > 0.05). Mean time from last colonoscopy
      to CRC was 32.7 months in the Finnish compared to 31.0 months in the non-Finnish
      (p > 0.05) and was therefore unaffected by the recommended colonoscopy interval.
      Differences in population incidence of CRC could not explain the lower point
      estimates for CRC in the Finnish series. Ten-year overall survival after CRC was
      similar for the Finnish and non-Finnish series (88% and 91%, respectively; p >
      0.05). CONCLUSIONS: The hypothesis that the high incidence of CRC in path_MLH1
      carriers was caused by a higher incidence in the Finnish series was not valid. We
      discuss whether the results were influenced by methodological shortcomings in our
      study or whether the assumption that a shorter interval between colonoscopies
      leads to a lower CRC incidence may be wrong. This second possibility is
      intriguing, because it suggests the dogma that CRC in path_MLH1 carriers develops
      from polyps that can be detected at colonoscopy and removed to prevent CRC may be
      erroneous. In view of the excellent 10-year overall survival in the Finnish and
      non-Finnish series we remain strong advocates of current surveillance practices
      for those with LS pending studies that will inform new recommendations on the
      best surveillance interval.

PMID- 29046740
TI  - Draft genome sequence and characterization of commensal Escherichia coli strain
      BG1 isolated from bovine gastro-intestinal tract.
AB  - Escherichia coli is the most abundant facultative anaerobic bacteria in the
      gastro-intestinal tract of mammals but can be responsible for intestinal
      infection due to acquisition of virulence factors. Genomes of pathogenic E. coli
      strains are widely described whereas those of bovine commensal E. coli strains
      are very scarce. Here, we report the genome sequence, annotation, and features of
      the commensal E. coli BG1 isolated from the gastro-intestinal tract of cattle.
      Whole genome sequencing analysis showed that BG1 has a chromosome of 4,782,107 bp
      coding for 4465 proteins and 97 RNAs. E. coli BG1 belonged to the serotype
      O159:H21, was classified in the phylogroup B1 and possessed the genetic
      information encoding "virulence factors" such as adherence systems, iron
      acquisition and flagella synthesis. A total of 12 adherence systems were detected
      reflecting the potential ability of BG1 to colonize different segments of the
      bovine gastro-intestinal tract. E. coli BG1 is unable to assimilate ethanolamine
      that confers a nutritional advantage to some pathogenic E. coli in the bovine
      gastro-intestinal tract. Genome analysis revealed the presence of i) 34 amino
      acids change due to non-synonymous SNPs among the genes encoding ethanolamine
      transport and assimilation, and ii) an additional predicted alpha helix inserted
      in cobalamin adenosyltransferase, a key enzyme required for ethanolamine
      assimilation. These modifications could explain the incapacity of BG1 to use
      ethanolamine. The BG1 genome can now be used as a reference (control strain) for
      subsequent evolution and comparative studies.

PMID- 29046742
TI  - Complete genome sequence of Paenibacillus yonginensis DCY84T, a novel plant
      Symbiont that promotes growth via induced systemic resistance.
AB  - This article reports the full genome sequence of Paenibacillus yonginensis DCY84T
      (KCTC33428, JCM19885), which is a Gram-positive rod-shaped bacterium isolated
      from humus soil of Yongin Forest in Gyeonggi Province, South Korea. The genome
      sequence of strain DCY84T provides greater understanding of the Paenibacillus
      species for practical use. This bacterium displays plant growth promotion via
      induced systemic resistance of abiotic stresses.

PMID- 29046741
TI  - Complete genome sequence of Thermotoga sp. strain RQ7.
AB  - Thermotoga sp. strain RQ7 is a member of the family Thermotogaceae in the order
      Thermotogales. It is a Gram negative, hyperthermophilic, and strictly anaerobic
      bacterium. It grows on diverse simple and complex carbohydrates and can use
      protons as the final electron acceptor. Its complete genome is composed of a
      chromosome of 1,851,618 bp and a plasmid of 846 bp. The chromosome contains 1906
      putative genes, including 1853 protein coding genes and 53 RNA genes. The genetic
      features pertaining to various lateral gene transfer mechanisms are analyzed. The
      genome carries a complete set of putative competence genes, 8 loci of CRISPRs,
      and a deletion of a well-conserved Type II R-M system.

PMID- 29046743
TI  - Post-Processing Partitions to Identify Domains of Modularity Optimization.
AB  - We introduce the Convex Hull of Admissible Modularity Partitions (CHAMP)
      algorithm to prune and prioritize different network community structures
      identified across multiple runs of possibly various computational heuristics.
      Given a set of partitions, CHAMP identifies the domain of modularity optimization
      for each partition-i.e., the parameter-space domain where it has the largest
      modularity relative to the input set-discarding partitions with empty domains to
      obtain the subset of partitions that are "admissible" candidate community
      structures that remain potentially optimal over indicated parameter domains.
      Importantly, CHAMP can be used for multi-dimensional parameter spaces, such as
      those for multilayer networks where one includes a resolution parameter and
      interlayer coupling. Using the results from CHAMP, a user can more appropriately
      select robust community structures by observing the sizes of domains of
      optimization and the pairwise comparisons between partitions in the admissible
      subset. We demonstrate the utility of CHAMP with several example networks. In
      these examples, CHAMP focuses attention onto pruned subsets of admissible
      partitions that are 20-to-1785 times smaller than the sets of unique partitions
      obtained by community detection heuristics that were input into CHAMP.

PMID- 29046745
TI  - The Bedside Index for Severity in Acute Pancreatitis: a systematic review of
      prospective studies to determine predictive performance.
AB  - Background: predicting the development of severe disease has remained a major
      challenge in management of acute pancreatitis. The Bedside Index for Severity in
      Acute Pancreatitis (BISAP) is easy to calculate from the data available in the
      first 24 hours. Here, we performed a systematic review to determine the
      prognostic accuracy of the BISAP for severe acute pancreatitis (SAP). Methods:
      major databases of biomedical publications were searched during the first week of
      October 2015. Two independent reviewers searched records in two phases. Studies
      that reported prognostic accuracy of the BISAP for SAP from prospective cohorts
      were included. The pooled area under the receiver operating curve (AUC) was
      calculated. Results: Twelve studies were included for data-synthesis and
      methodology quality assessment was performed for 10. All the studies had enrolled
      consecutive patients, had a broad spectrum of the disease severity, reported
      explicit interpretation of the predictor, outcome of interest was well defined
      and had adequate follow-up. Blinded outcome assessment was reported in only one
      study. The pooled AUC was 0.85 (95% CI 0.80-0.90). There was significant
      heterogeneity, I2 86.6%. Studies using revised Atlanta classification in defining
      SAP had a pooled AUC of 0.92 (95% CI, 0.90-0.95), but heterogeneity persisted, I2
      67%. Subgroup analysis based on rate of SAP (>20% vs <20%) did not eliminate the
      heterogeneity. Conclusion: the BISAP has very good predictive performance for SAP
      across different patient population and etiologies. Studies to evaluate the
      impact of incorporating the BISAP into clinical practice to improve outcome in
      acute pancreatitis are needed before adoption could be advocated with confidence.

PMID- 29046744
TI  - Clinical and epidemiological characteristics of patients with acute drug
      intoxication admitted to ICU.
AB  - Background: Drug overdose continues to be the most common cause of acute
      poisoning worldwide. There has been a substantial increase in drug overdose
      incidence and prevalence over the past decade, probably as a result of the
      emergence of new synthetic designer drugs. The purpose of this study is to
      describe the clinical and epidemiological characteristics of patients with acute
      drug intoxication admitted to the Intensive Care Unit (ICU). Methods: A single
      center, prospective, observational study was conducted among all adult patients
      with clinical signs suggestive of acute drug intoxication admitted from the
      Emergency Department (ED) to ICU during a 6-month period (September to March).
      Results: Sixty-five patients were admitted. Their median age was 49 years (mean
      48.2, range 20-72), and the majority were male (48, 74%). Median Sequential Organ
      Failure Assessment (SOFA) score on admission to ICU was 6 (mean 6, range 0-13).
      Fifty-five patients (85%) had a positive urine and/or serum toxicology screen.
      Most commonly detected substances were: opiates (18, 33%), cocaine (13, 24%),
      methadone (12, 22%), benzodiazepines (10, 18%), and marijuana (9, 16%). In 16
      patients (29%), >1 substance was isolated. Twenty-three patients (35%) had
      negative urine toxicology screen. Ethyl alcohol was detected in the serum of 23
      patients (35%). Five patients (8%) expired in ICU. Conclusion: Classic
      recreational drugs remain the most common substances involved in acute drug
      poisoning. More sensitive detection methods are warranted to identify new
      designer drugs of abuse such as synthetic cannabinoids.

PMID- 29046746
TI  - Perspectives on non-neoformans cryptococcal opportunistic infections.
AB  - Non-neoformans Cryptococcus species, including C. laurentii and C. albidus, have
      historically been classified as exclusively saprophytic. However, recent studies
      have increasingly implicated these organisms as the causative agent of
      opportunistic infections in humans. Herein, the case is presented of C. laurentii
      meningitis in a critically ill patient receiving corticosteroids. C. laurentii
      has been implicated in an additional 18 cases of opportunistic infection,
      predominantly of the skin, bloodstream, and central nervous system. The most
      clinically significant risk factors for non-neoformans cryptococcal infections
      include: impaired cell-mediated immunity, recent corticosteroid use, and invasive
      catheter placement. This article provides a comprehensive review of the clinical
      relevance, pathogenesis, risk factors, and treatment of non-neoformans
      Cryptococcus species.

PMID- 29046747
TI  - Ventricular fibrillation due to overdose of loperamide, the "poor man's
      methadone".
AB  - Loperamide is an over-the-counter antidiarrheal agent that is considered by many
      patients to be safe, but has been used as a drug of abuse due to its opioid
      properties. However, cardiotoxicity has been reported, prompting the FDA to
      release a warning regarding the arrhythmogenic potential of loperamide. We
      present a case of a 38-year-old female presenting with cardiac arrest thought to
      be secondary to abuse of the loperamide that she was using to alleviate the
      heroin withdrawal symptoms. Cardiac ischemia and other drug toxicities were ruled
      out. Loperamide induces QTc prolongation and cardiac dysrhythmias. She had
      recurrent ventricular arrhythmias with multiple cardiac arrests. The persistence
      of the cardiotoxicity for a longer duration than previously reported in the
      literature is unique in this clinical presentation. We also highlight the
      potential mechanisms for loperamide cardiotoxicity and its challenging
      management. Abbreviations: ACLS: Advanced cardiac life support; GI:
      Gastrointestinal.

PMID- 29046748
TI  - beta-thalassemia minor, carbohydrate malabsorption and histamine intolerance.
AB  - Background: beta-thalassemia minor is characterized by reduced beta-haemoglobin
      chain synthesis and sometimes mild anaemia, although carriers of beta-thalassemia
      minorare usually clinically asymptomatic.Nonspecific abdominal complaints may be
      caused by gastrointestinal carbohydrate malabsorption (lactose and fructose)
      and/or malabsorption of biogenic amines (histamine), or proteins (gluten).
      Objectives: We report on two patients with beta-thalassemia minor suffering
      nonspecific abdominal symptoms due to a carbohydrate and histamine malabsorption.
      Design/methods: The diagnosis of beta-thalassemia minorwas done with peripheral
      blood smear and cellulose acetate electrophoresis. Carbohydrate malabsorption was
      diagnosed with hydrogen breath tests and, histamine intolerance (HIT) with a
      serum diamine oxidase value <10 U/ml and more than two gastrointestinal symptoms
      described for HIT. Conclusion: The symptoms of gastrointestinal malabsorption in
      these two patients with beta-thalassemia minor were treated successfully with an
      individually-tailored diet free of symptom causing carbohydrates and histamine.

PMID- 29046749
TI  - An unusual case of chronic lymphocytic leukemia, multiple myeloma and cardiac
      amyloidosis.
AB  - Light chain amyloidosis has very rarely been reported in association with chronic
      lymphocytic leukemia (CLL). We reported on a 76-years-old female who presented
      with simultaneous kappa-restricted chronic lymphocytic leukemia (CLL) and a
      lambda-restricted multiple myeloma with plasma cells causing AL amyloidosis
      involving the heart. While monoclonal immunoglobulins occasionallyproduced by CLL
      have previously been implicated in AL amyloidosis, there only a few cases
      reported of AL amyloidosis resulting from a distinct plasma cell dyscrasia that
      is not clonally related to the concurrent CLL.

PMID- 29046750
TI  - Metastasis to the pancreas and stomach from a breast cancer primary: a case
      report.
AB  - A 60-year-old female with an unknown family history initially presented with
      signs and symptoms concerning for gastrointestinal cancer. Regular breast cancer
      screening and subsequent work-up around this time demonstrated the presence of
      T2N1 stage II triple positive ductal adenocarcinoma of the left breast. Follow-up
      imaging for her gastrointestinal symptoms demonstrated a 3.5 cm solitary mass in
      the pancreas and diffuse thickening of the stomach wall. Biopsies of the
      gastrointestinal lesions were identified as metastatic foci of the breast cancer
      primary. Breast cancer metastases to the stomach and to the pancreas are both
      very rare events. Of the breast cancer primaries that do metastasize to the
      gastrointestinal system, it is unusual for the primary to be ductal
      adenocarcinoma. The rapid succession of diagnosing the primary source of breast
      cancer simultaneously with its metastases is also unusual. Timely identification
      and appropriate management of these rare metastases was made possible due to
      routine breast cancer screening.

PMID- 29046751
TI  - Case series of multiple primary cancers in single individuals: diagnostic and
      therapeutic dilemmas.
AB  - Background and Objectives: Cancer recurrence represents treatment failure; the
      development of new primary tumors is suggestive of persistent exposure to
      etiological risk factors or genetic predisposition due to mutations in multiple
      cell lines. Case presentation/Design/Methods: The first case is a 65-years-old
      Caucasian male who presented with esophageal and lung cancer diagnosed
      synchronously. Smoking was the common risk factor for both cancers, underscoring
      field cancerization. The diagnosis and management was a challenge and different
      from either cancer presenting alone. Multidisciplinary approach was used and led
      to good outcomes. The second case is a 72-years-old Caucasian male presenting a
      rare dilemma of genetic mutation leading to multiple primary gastrointestinal
      cancers in a single individual. The gene explaining this group of cancers has not
      been diagnosed yet and the field needs to be explored further. Conclusion:
      Multiple primary cancers can be secondary to a common environmental risk factor
      or genetic mutations.

PMID- 29046752
TI  - An exceedingly rare adrenal collision tumor: adrenal adenoma-metastatic breast
      cancer-myelolipoma.
AB  - Adrenal collision tumors (ACTs), in which distinct tumors coexist without
      histological intermingling in the same adrenal gland, are rare and their actual
      prevalence is unknown. ACTs commonly consist of adrenal cortical adenoma,
      myelolipoma, or metastatic malignant tumor. We report a 58-year-old woman with a
      past history of breast cancer, who presented with a 1 month history of fevers,
      chills, and abdominal fullness. The physical examination and the laboratory data
      including endocrine studies were unremarkable. Computed tomography of the abdomen
      showed a right adrenal gland mass, and a laparoscopic right adrenalectomy was
      performed. Histological and immunohistochemical examinations revealed three
      distinct tumors: an adrenal cortical adenoma, a myelolipoma, and metastatic
      breast tumors. Breast cancer metastases are rare in the adrenal gland and exist
      as ACTs only in exceptionally rare cases. To our knowledge, this is the first
      reported case of coexisting metastatic breast tumors, adrenal adenoma, and
      myelolipoma in the same adrenal gland.

PMID- 29046753
TI  - Melioidosis: the great mimicker.
AB  - Melioidosis is an infectious disease endemic in Northern Australia and South East
      Asia. It is associated with high degrees of morbidity and mortality. On average,
      around five cases are diagnosed annually in the USA. Diagnosis remains a
      challenge, as it mimics many other conditions, especially tuberculosis, hence its
      other name, the 'great mimicker.' The present case involves a recent traveler to
      the Philippines, who presented with episodic fevers and weight loss to his
      primary care physician. Blood cultures ordered grew Burkholderia pseudomallei.
      Primary care physicians should suspect melioidosis in symptomatic patients with
      travel history to endemic areas.

PMID- 29046754
TI  - Splenic infarct in a patient with Infectious Mononucleosis: a rare presentation.
AB  - We report a case of a 25-year-old obese, currently smoking, female diagnosed with
      EBV infectious mononucleosis. The patient complained of sudden onset abdominal
      pain with progressively increasing intensity in the left upper quadrant.
      Abdominal CT scan showed a wedge infarct of the spleen. We present this rare case
      that EBV may cause splenic infarct in young adults.

PMID- 29046755
TI  - Some neck swellings are serious; a case of Lemierre's Syndrome.
AB  - Lemierre's syndrome also termed post-anginal septicemia, is a disease
      characterized by internal jugular septic thrombophlebitis leading to
      Fusobacterium septicemia with multiple metastatic foci following an oropharyngeal
      infection. Diagnosis and management is challenging and can result in fatal
      consequences due to potential multisystem involvement and multiple complications.
      We describe here a case of Lemierre's syndrome with multifocal pneumonia, acute
      renal failure and protracted course of illness over forty days with successful
      recovery. A brief overview of literature is also presented.

PMID- 29046756
TI  - Pneumatosis of the esophagus and intestines with portal venous air: a rare
      presentation.
AB  - Pneumatosis intestinalis is a radiographic finding that represents a spectrum of
      conditions ranging from benign disease to abdominal sepsis and death. Along with
      portal venous gas, it is generally considered an ominous sign prompting emergency
      operative intervention. We report a rare case showing that nonoperative therapy
      can be considered in a seriously ill patient with esophageal, gastric and portal
      venous air.

PMID- 29046757
TI  - Multiple left anterior descending coronary artery to left ventricular fistula - A
      case series and literature review.
AB  - Coronary artery fistulas (CAFs) are found in 0.3-0.8% of patients who undergo
      coronary angiography. CAFs are defined as single or multiple, small or large
      direct communications that arise from one or more coronary arteries and enter
      into one of the four cardiac chambers or major vessels. We present two cases of
      multiple coronary artery fistulas arising from diagonal and left anterior
      descending (LAD) branches of left coronary artery draining into the left
      ventricle. In both the cases, No intervention was performed. Of the congenital
      fistulas, two major groups are identified: solitary CAFs or coronary artery-left
      ventricular multiple micro-fistulas (CALVMMFs). Noninvasive techniques such as
      transthoracic echocardiography, transesophageal echocardiography and magnetic
      resonance imaging are becoming increasingly popular for diagnosis and follow-up
      of CAFs. Despite the advent of these newer non-invasive modalities, coronary
      angiography remains the gold standard for diagnosis. Treatment of CAFs is
      indicated when the patients are symptomatic with left ventricular volume
      overload, myocardial ischemia, left ventricular dysfunction or in the presence of
      a large or increasing left-to-right shunt. If the fistula is small and
      hemodynamically insignificant, it can be managed with conservative management.
      Multiple left anterior descending to left ventricle (LV) fistulas are extremely
      rare and, as per our literature review, we noted only a few case reports of
      coronary artery fistulas between branches of LAD and left ventricle.

PMID- 29046758
TI  - Coronary artery ectasia presenting with acute inferior wall myocardial infarction
      in a young adult.
AB  - Coronary artery ectasia (CAE), a variant of coronary artery anomalies, is a rare
      clinical entity. Although atherosclerotic coronary artery disease (CAD) is the
      most common cause of acute coronary syndrome (ACS), CAE also conveys a relatively
      high risk for potentially life-threatening cardiac events. We report a case of a
      35-year-old male with two-vessel CAE, who presented with acute inferior wall ST
      election myocardial infarction (STEMI). After initiating medical therapy
      including bivalirudin, emergent percutaneous coronary intervention (PCI) with
      stenting of postero-lateral branch of right coronary artery (RCA) was performed.
      Coronary angiography also showed diffuse ectasia of RCA and left anterior
      descending artery (LAD). The patient tolerated the procedure well and was
      discharged on appropriate medical therapy. He was followed-up at one month, with
      no resulting cardiac events. This case highlights the importance of CAE
      awareness. CAE has drawn the attention of clinicians because of its clinical
      implications, as well as its seemingly higher prevalence, due to the abundant use
      of coronary angiograms and advanced cardiac imaging in the contemporary world.
      Albeit there has been much progress in the understanding and management of the
      disease, questions still remain regarding the exact pathophysiology, management
      guidelines and prognosis of CAE, which are worth further study.

PMID- 29046759
TI  - Copper deficiency, a new triad: anemia, leucopenia, and myeloneuropathy.
AB  - Clinical copper deficiency is now more frequently recognized. Hematologically, it
      can present as anemia (microcytic, normocytic, or macrocytic) and neutropenia.
      Thrombocytopenia is relatively rare. Neurologically, it can manifest as
      myelopathy and peripheral neuropathy simulating subacute combined degeneration.
      Bone marrow findings can mimic myelodysplasia resulting in occasional
      inappropriate referral for bone marrow transplantation. Other conditions with
      similar presentations include infections, drug toxicity, autoimmunity, B12
      deficiency, folate deficiency, myelodysplastic syndrome, aplastic anemia, and
      lymphoma with bone marrow involvement. Hematological, but not neurological,
      manifestations respond promptly to copper replacement, making early diagnosis
      essential for good outcome. Common risk factors for copper deficiency are foregut
      surgery, dietary deficiency, enteropathies with malabsorption, and prolonged
      intravenous nutrition (total parenteral nutrition). We present a unique case of
      copper deficiency, with no apparent known risk factors.

PMID- 29046760
TI  - An atypical subacute presentation of posterior reversible encephalopathy
      syndrome.
AB  - Posterior reversible encephalopathy syndrome (PRES) characteristically presents
      with rapid onset of headache, seizure, encephalopathy, and visual changes, along
      with evidence of parieto-occipital vasogenic edema on magnetic resonance imaging.
      We describe the case of a 41-year-old female with a protracted presentation of
      two of the four classic PRES symptoms, which were not immediately recognized as
      PRES due to the presence of multiple other comorbidities and reasons for
      encephalopathy. This case highlights the possibility of atypical presentations of
      PRES and the diagnostic challenges in making this clinical diagnosis when
      competing diagnoses are present.

PMID- 29046761
TI  - Loperamide abuse and cardiotoxicity.

PMID- 29046762
TI  - A commentary on operamide and cardiotoxicity.

PMID- 29046763
TI  - Abstract Book: ISEV2017.

PMID- 29046764
TI  - Dynamics of Change and Change in Dynamics.
AB  - A framework is presented for building and testing models of dynamic regulation by
      categorizing sources of differences between theories of dynamics. A distinction
      is made between the dynamics of change, i.e., how a system self-regulates on a
      short time scale, and change in dynamics, i.e., how those dynamics may themselves
      change over a longer time scale. In order to clarify the categories, models are
      first built to estimate individual differences in equilibrium value and
      equilibrium change. Next, models are presented in which there are individual
      differences in parameters of dynamics such as frequency of fluctuations, damping
      of fluctuations, and amplitude of fluctuations. Finally, models for within-person
      change in dynamics over time are proposed. Simulations demonstrating feasibility
      of these models are presented and OpenMx scripts for fitting these models have
      been made available in a downloadable archive along with scripts to simulate data
      so that a researcher may test a selected models' feasibility within a chosen
      experimental design.

PMID- 29046766
TI  - PONV prevention: still not enough.

PMID- 29046765
TI  - Is ultrasound-guided procedure entirely reliable?

PMID- 29046767
TI  - Can we trust the results of scientific papers?

PMID- 29046768
TI  - Smartphones and e-tablets in perioperative medicine.
AB  - Smartphones and electronic tablets (e-tablets) have become ubiquitous devices.
      Their ease of use, smartness, accessibility, mobility and connectivity create
      unique opportunities to improve quality of surgical care from prehabilitation to
      rehabilitation. Before surgery, digital applications (Apps), serious games and
      text messaging may help for a better control of risk factors (hypertension,
      overweight), for smoking cessation, and for optimizing adherence to preoperative
      recommendations (e.g., regarding anticoagulation or antihypertensive treatments).
      During surgery, Apps may help to rationalize fluid management and estimate blood
      loss. After surgery, smartphones and/or connected sensors (pulse oximeter,
      adhesive path, electronic tattoo, bioimpedance necklace) can be used to monitor
      body temperature, heart rate, heart rate variability (detection of cardiac
      arrhythmia), respiratory rate, arterial oxygen saturation and thoracic fluid
      content. Therefore, these tools have potential for the early detection of
      infectious, cardiac and respiratory complications in the wards and from home.
      When connected to echo probes, smartphones and e-tablets can also be used as
      ultrasound devices during central venous catheter insertion, for peripheral nerve
      blocks, and to perform echocardiography in patients developing cardiac
      complications. Finally, electronic checklists now exist as Apps to enhance
      communication between patients and healthcare professionals, and to track and
      record step by step each element of the surgical journey. Studies are now
      urgently needed to investigate whether this digital revolution can translate into
      a better outcome, an earlier detection of postoperative complications, a decrease
      in hospital readmissions and in health care costs.

PMID- 29046770
TI  - Assessment of risk of bias in quasi-randomized controlled trials and randomized
      controlled trials reported in the Korean Journal of Anesthesiology between 2010
      and 2016.
AB  - Bias affects the true intervention effect in randomized controlled trials (RCTs),
      making the results unreliable. We evaluated the risk of bias (ROB) of quasi-RCTs
      or RCTs reported in the Korean Journal of Anesthesiology (KJA) between 2010 and
      2016. Six kinds of bias (selection, performance, detection, attrition, reporting,
      and other biases) were evaluated by determining low, unclear, or high ROB for
      eight domains (random sequence generation, allocation concealment, blinding of
      participants, blinding of personnel, blinding of outcome assessment, incomplete
      outcome data, selective reporting, and other bias) according to publication year.
      We identified 296 quasi-RCTs or RCTs. Random sequence generation was performed
      better than allocation concealment (51.7% vs. 20.9% for the proportion of low
      ROB, P < 0.001 and P = 0.943 for trend, respectively). Blinding of outcome
      assessment was superior to blinding of participants and personnel (42.9% vs.
      15.5% and 23.0% for the proportion of low ROB, P = 0.026 vs. P = 0.003 and 0.896
      for trend, respectively). Handling of incomplete outcome data was performed best
      with the highest proportion of low ROB (84.8%). Selective reporting had the
      lowest proportion of low ROB (4.7%). However, the ROB improved year by year (P <
      0.001 for trend). Authors and reviewers should consider allocation concealment
      after random sequence generation, blinding of participants and personnel, and
      full reporting of results to improve the quality of RCTs submitted hereafter for
      publication in the KJA.

PMID- 29046769
TI  - Factors that affect the onset of action of non-depolarizing neuromuscular
      blocking agents.
AB  - Neuromuscular blockade plays an important role in the safe management of patient
      airways, surgical field improvement, and respiratory care. Rapid-sequence
      induction of anesthesia is indispensable to emergency surgery and obstetric
      anesthesia, and its purpose is to obtain a stable airway, adequate depth of
      anesthesia, and appropriate respiration within a short period of time without
      causing irritation or damage to the patient. There has been a continued search
      for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action.
      Factors that affect the onset time include the potency of the NMBDs, the rate of
      NMBDs reaching the effect site, the onset time by dose control, metabolism and
      elimination of NMBDs, buffered diffusion to the effect site, nicotinic
      acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh)
      production and release at the neuromuscular junction, drugs that inhibit plasma
      cholinesterase, presynaptic receptors responsible for ACh release at the
      neuromuscular junction, anesthetics or drugs that affect muscle contractility,
      site and methods for monitoring neuromuscular function, individual variability,
      and coexisting disease. NMBDs with rapid onset without major adverse events are
      expected in the next few years, and the development of lower potency NMBDs will
      continue. Anesthesiologists should be aware of the use of NMBDs in the management
      of anesthesia. The choice of NMBD and determination of the appropriate dosage to
      modulate neuromuscular blockade characteristics such as onset time and duration
      of neuromuscular blockade should be considered along with factors that affect the
      effects of the NMBDs. In this review, we discuss the factors that affect the
      onset time of NMBDs.

PMID- 29046771
TI  - A comparison of palonosetron and dexamethasone for postoperative nausea and
      vomiting in orthopedic patients receiving patient-controlled epidural analgesia.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the major concerns
      after anesthesia and surgery, and it may be more frequent in orthopedic patients
      receiving patient-controlled epidural analgesia (PCEA). The purpose of this study
      was to compare the effect of palonosetron and dexamethasone on the prevention of
      PONV in patients undergoing total joint arthroplasty and receiving PCEA. METHODS:
      Patients scheduled for total hip or knee arthroplasty under spinal
      anesthesia/PCEA were randomly allocated to receive either intravenous
      palonosetron (0.075 mg, n = 50) or dexamethasone (5 mg, n = 50). Treatments were
      administered intravenously to the patients 30 min before the beginning of
      surgery. The total incidence of PONV and incidence in each time period, severity
      of nausea, need for rescue anti-emetics, pain score, and adverse effects during
      the first 48 h postoperatively were evaluated. RESULTS: The total incidence of
      PONV was lower in the palonosetron group compared with the dexamethasone group
      (18.4% vs. 36.7%, P = 0.042), but there were no statistically significant
      differences in incidence between the groups at all time points. No significant
      intergroup differences were observed in the severity of nausea, use of rescue
      anti-emetics, pain score, and adverse effects. CONCLUSIONS: Although there were
      no significant differences in the incidence of PONV between the treatment groups
      at all time points, intravenous palonosetron reduced the total incidence of PONV
      in orthopedic patients receiving PCEA compared with dexamethasone.

PMID- 29046772
TI  - Effects of acute kidney injury after liver resection on long-term outcomes.
AB  - BACKGROUND: To investigate the effects of acute kidney injury (AKI) after liver
      resection on the long-term outcome, including mortality and renal dysfunction
      after hospital discharge. METHODS: We conducted a historical cohort study of
      patients who underwent liver resection for hepatocellular carcinoma with
      sevoflurane anesthesia between January 2004 and October 2011, survived the
      hospital stay, and were followed for at least 3 years or died within 3 years
      after hospital discharge. AKI was diagnosed based on the Acute Kidney Injury
      Network classification within 72 hours postoperatively. In addition to the data
      obtained during hospitalization, serum creatinine concentration data were
      collected and the glomerular filtration rate (GFR) was estimated after hospital
      discharge. RESULTS: AKI patients (63%, P = 0.002) were more likely to reach the
      threshold of an estimated GFR (eGFR) of 45 ml/min/1.73 m2 within 3 years than non
      AKI patients (31%) although there was no significant difference in mortality (33%
      vs. 29%). Cox proportional hazard regression analysis showed that postoperative
      AKI was significantly associated with the composite outcome of mortality or an
      eGFR of 45 ml/min/1.73 m2 (95% CI of hazard ratio, 1.05-2.96, P = 0.033), but not
      with mortality (P = 0.699), the composite outcome of mortality or an eGFR of 60
      ml/min/1.73 m2 (P =0.347). CONCLUSIONS: After liver resection, AKI patients may
      be at higher risk of mortality or moderate renal dysfunction within 3 years.
      These findings suggest that even after discharge from the hospital, patients who
      suffered AKI after liver resection may need to be followed-up regarding renal
      function in the long term.

PMID- 29046774
TI  - Role of WhatsApp-based discussions in improving residents' knowledge of post
      operative pain management: a pilot study.
AB  - BACKGROUND: To provide a platform for the dissemination of basic knowledge of
      pain management, a WhatsApp group was created by residents and consultants.
      Common clinical scenarios, resident queries, and important instructions to be
      followed by residents with respect to running the Acute Pain Service were
      discussed in the group. This study evaluates the benefits of this interaction.
      METHODS: This study was approved by the hospital ethics board and was registered
      with the Clinical Trial Registry of India. Second- and third-year anesthesia
      residents were included in a WhatsApp group, along with consultants (board
      certified anesthesiologists with a special interest in pain). Pain knowledge
      assessment was performed pre- and post-discussion using a standard 22-point
      questionnaire. A feedback form, which included self-rated confidence scores (1
      10, 10-most confident) and opinions about the 3-month WhatsApp discussion, was
      collected. Improvements in the documentation in clinical sheets post-discussion
      were also analyzed. RESULTS: A total of 38 residents were included in the
      WhatsApp group. An improvement in the percentage of correct answers from 69.1%
      (pre-discussion) to 73.6% (post-discussion) was observed (P = 0.031).
      Improvements in the self-rated residents' confidence levels were also noted (P <
      0.05). A total of 37 residents felt that the WhatsApp-based discussion was
      useful. Documentation of the details of epidural blockade in clinical sheets
      improved from 30% to 100%. CONCLUSIONS: The WhatsApp discussion improved
      residents' knowledge and confidence levels, and also resulted in improved
      documentation of essential details in the clinical notes. This form of education
      is promising and should be explored in future studies.

PMID- 29046773
TI  - Dexamethasone alone versus in combination with intra-operative super-hydration
      for postoperative nausea and vomiting prophylaxis in female patients undergoing
      laparoscopic cholecystectomy: a randomized clinical trial.
AB  - BACKGROUND: Dexamethasone has a prophylactic effect on postoperative nausea and
      vomiting (PONV) and perioperative hydration is believed to play a role in PONV
      prophylaxis. This study was performed to examine the combined effects of pre
      induction dexamethasone plus super-hydration on PONV and pain following
      laparoscopic cholecystectomy (LC). METHODS: A total of 100 female patients
      undergoing LC were enrolled and randomized equally into two groups. Group DF
      received 5 mg dexamethasone (pre-induction) plus 30 ml/kg Ringer's lactate
      (intraoperative) and group D received 5 mg dexamethasone (pre-induction) alone.
      Anesthetic and surgical managements were standardized for all patients. The
      incidence and severity of PONV, and intra and post-operative analgesic and
      postoperative antiemetic consumption, were assessed during the first 24 h
      postoperatively. Post-anesthesia care unit (PACU) stay and aggregated 24 h pain
      scores were calculated. RESULTS: Group DF had significantly lower PONV than group
      D (P = 0.03). The number of patients with the lowest PONV score was significantly
      increased in group DF (P = 0.03). Ondansetron consumption was significantly lower
      in group DF (P < 0.0001). The mean accumulated 24 h pain scores were
      significantly lower in group DF compared to group D (P < 0.0001). The time to
      first analgesic request was significantly longer in group DF than group D (P <
      0.0001). In addition, total meperidine consumption during the first postoperative
      24 h was significantly lower in group DF than group D (P = 0.002). CONCLUSIONS:
      In female patients undergoing LC, pre-induction with 5 mg dexamethasone plus
      intraoperative 30 ml/kg Ringer's lactate solution decreased PONV and pain during
      the first 24 h postoperatively compared to 5 mg dexamethasone alone.

PMID- 29046775
TI  - Effect of preoperative incentive spirometry on fentanyl-induced cough: a
      prospective, randomized, controlled study.
AB  - BACKGROUND: Fentanyl-induced cough (FIC) has a reported incidence of 13-65% on
      induction of anesthesia. Incentive spirometry (IS) creates forceful inspiration,
      while stretching pulmonary receptors. We postulated that spirometry just before
      the fentanyl (F) bolus would decrease the incidence and severity of FIC. METHODS:
      This study enrolled 200 patients aged 18-60 years and with American Society of
      Anesthesiologists status I or II. The patients were allocated to two groups of
      100 patients each depending on whether they received preoperative incentive
      spirometry before fentanyl administration. Patients in the F+IS group performed
      incentive spirometry 10 times just before an intravenous bolus of 3 ug/kg
      fentanyl in the operating room. The onset time and number of coughs after
      fentanyl injection were recorded as primary outcomes. Any significant changes in
      blood pressure, heart rate, or adverse effects of the drug were recorded as
      secondary outcomes. RESULTS: Patients in the F+IS group had a significantly lower
      incidence of FIC than in the F group (6% vs. 26%) (P < 0.05). The severity of
      cough in the F+IS group was also significantly lower than that in group F (mild,
      5 vs. 17; moderate 1 vs. 7; severe, 0 vs. 2) (P < 0.05). The median onset time
      was comparable in both groups (9 s [range: 6-12 s] in both groups). CONCLUSIONS:
      Preoperative incentive spirometry significantly reduces the incidence and
      severity of FIC when performed just before fentanyl administration.

PMID- 29046776
TI  - The safety of endoscopic esophageal procedures under general anesthesia.
AB  - BACKGROUND: With the increasing demand for general anesthesia for endoscopic
      esophageal procedures, anesthesiologists should understand the clinical
      characteristics of post-procedural complications (PPCs). METHODS: We
      retrospectively investigated the incidence of and risk factors associated with
      PPCs of endoscopic esophageal procedures performed under general anesthesia from
      July 2013 to November 2016. The final analysis included 129 patients; 114 who
      underwent esophageal endoscopic dissection for esophageal tumors and 15 cases of
      peroral endoscopic myotomy for achalasia. Frank perforation during the procedure
      was defined as an endoscopically recognizable or clinically detected perforation
      during the procedures. A multivariable logistic regression analysis was conducted
      to identify independent risk factors for PPCs. RESULTS: The overall incidence of
      PPCs was 19.4% (25/129). All of the PPCs were managed successfully with
      conservative measures. The most common PPC was symptomatic, radiologically
      documented atelectasis (11/25, 44.0%), followed by esophageal perforation-related
      PPCs (symptomatic pneumomediastinum or pneumoperitoneum; 9/25, 36.0%). In the
      multivariable analysis, frank perforation during the procedure was the only
      independent risk factor for PPCs (odds ratio, 8.470, 95% CI, 2.051-34.974, P =
      0.003). Although frank perforation during the procedure occurred in 13 patients,
      38.5% (5/13) of them did not develop any clinical sequelae after their
      procedures. Compared with patients without PPCs, patients who developed PPCs took
      longer to their first oral intake and had prolonged hospital stays (P = 0.047 and
      0.026, respectively). CONCLUSIONS: Iatrogenic perforation during endoscopic
      esophageal procedures under general anesthesia was the only independent risk
      factor for PPCs; therefore, proactive measures and close follow-up are necessary.

PMID- 29046777
TI  - Effect of palmitoylethanolamide on inflammatory and neuropathic pain in rats.
AB  - BACKGROUND: A growing body of evidence suggests that neuroinflammation, which is
      characterized by infiltration of immune cells, activation of mast cells and glial
      cells, and production of inflammatory mediators in the peripheral and central
      nervous systems, plays an important role in the induction and maintenance of
      chronic pain. Palmitoylethanolamide (PEA), which is a type of N-acylethanolamide
      and a lipid, has an anti-inflammatory effect. Relative to the anti-inflammatory
      effect, little is known about its analgesic effect in chronic pain. This study
      aimed to determine whether PEA relieves chronic inflammatory and neuropathic
      pain. METHODS: Male Sprague-Dawley rats were injured by transection of the left
      L5 and L6 spinal nerves to induce neuropathic pain or were injected with
      monoiodoacetic acid into the synovial cavity of knee joints to induce
      inflammatory pain. To assess the degree of pain, two kinds of stimuli - pressing
      von Frey filaments and wetting with acetone - were applied to the plantar surface
      of the rat to measure mechanical and cold sensitivity, respectively. Pain was
      measured by assessing behavioral responses, including paw withdrawal response
      threshold and paw withdrawal frequency upon stimulation. RESULTS: Neuropathic
      pain caused by spinal nerve transection (SNT) decreased the mechanical threshold
      and increased the frequency of response to acetone application. But, cold
      allodynia caused by SNT did not decrease the withdrawal frequency. Mechanical
      hyperalgesia caused by chronic inflammation was significantly reduced by both
      intraperitoneal and intra-articular injections of PEA. CONCLUSIONS: These
      outcomes revealed that PEA might be effective in relieving inflammatory and
      neuropathic pain, especially pain induced by mechanical hyperalgesia, but not
      cold allodynia.

PMID- 29046778
TI  - Ultrasound-guided percutaneous cryoneurolysis providing postoperative analgesia
      lasting many weeks following a single administration: a replacement for
      continuous peripheral nerve blocks?: a case report.
AB  - Cryoneurolysis entails using low temperatures to reversibly ablate nerves, with a
      subsequent analgesia duration measured in weeks or months. Previously, clinical
      applications for acute pain were limited because treatment originally required
      exposing the target nerve surgically. However, three developments have now made
      it possible to provide prolonged postoperative analgesia by cryoneurolysis: 1)
      new portable, hand-held cryoneurolysis devices, 2) ultrasound machine
      proliferation, and, 3) anesthesiologists trained in ultrasound-guided peripheral
      nerve block administration. This report is the first to describe the use of a
      single preoperative administration of ultrasound-guided percutaneous
      cryoneurolysis to provide multiple weeks of analgesia following shoulder rotator
      cuff repair and total knee arthroplasty. Considering the significant benefits of
      cryoanalgesia relative to continuous peripheral nerve blocks (e.g., lack of
      catheter/pump care, extremely long duration), this analgesic modality may be a
      practical alternative for the treatment of prolonged post-surgical pain in a
      select group of surgical patients.

PMID- 29046779
TI  - Anesthetic management during the first combined heart-liver transplant performed
      in Korea: a case report.
AB  - Herein, we describe the anesthetic management during the first combined heart
      liver transplant (CHLT) performed in Korea. Though CHLT is a rare procedure,
      accumulating evidence suggests that it is a feasible option for patients with
      coexisting heart and liver failure. A 45-year-old female patient presented with
      severe cardiac dysfunction requiring extracorporeal membrane oxygenation (ECMO)
      support and secondary congestive hepatopathy. The patient underwent consecutive
      heart and liver transplantation using extracorporeal circulatory devices-heart
      transplant with cardiopulmonary bypass, and liver transplant with peripheral
      ECMO. In this case report, we focus on the specific anesthetic considerations for
      CHLT pertaining to the challenges associated with dual pathophysiology.

PMID- 29046780
TI  - Myoclonus of ipsilateral upper extremity after ultrasound-guided supraclavicular
      brachial plexus block with mepivacaine.

PMID- 29046781
TI  - Diagnosis of pulmonary embolism due to the use of interscalene block.

PMID- 29046782
TI  - Assessment of the potential for resistance to antimicrobial violet-blue light in
      Staphylococcus aureus.
AB  - BACKGROUND: Antimicrobial violet-blue light in the region of 405 nm is emerging
      as an alternative technology for hospital decontamination and clinical treatment.
      The mechanism of action is the excitation of endogenous porphyrins within exposed
      microorganisms, resulting in ROS generation, oxidative damage and cell death.
      Although resistance to 405 nm light is not thought likely, little evidence has
      been published to support this. This study was designed to establish if there is
      potential for tolerance development, using the nosocomial pathogen Staphylococcus
      aureus as the model organism. METHODS: The first stage of this study investigated
      the potential for S. aureus to develop tolerance to high-intensity 405 nm light
      if pre-cultured in low-level stress violet-blue light (<=1 mW/cm2) conditions.
      Secondly, the potential for tolerance development in bacteria subjected to
      repeated sub-lethal exposure was compared by carrying out 15 cycles of exposure
      to high-intensity 405 nm light, using a sub-lethal dose of 108 J/cm2.
      Inactivation kinetics and antibiotic susceptibility were also compared. RESULTS:
      When cultured in low-level violet-blue light conditions, S. aureus required a
      greater dose of high-intensity 405 nm light for complete inactivation, however
      this did not increase with multiple (3) low-stress cultivations. Repeated sub
      lethal exposures indicated no evidence of bacterial tolerance to 405 nm light.
      After 15 sub-lethal exposures 1.2 and 1.4 log10 reductions were achieved for MSSA
      and MRSA respectively, which were not significantly different to the initial 1.3
      log10 reductions achieved (P = 0.242 & 0.116, respectively). Antibiotic
      susceptibility was unaffected, with the maximum change in zone of inhibition
      being +/- 2 mm. CONCLUSIONS: Repeated sub-lethal exposure of non-proliferating S.
      aureus populations did not affect the susceptibility of the organism to 405 nm
      light, nor to antibiotics. Culture in low-level violet-blue light prior to 405 nm
      light exposure may increase oxidative stress responses in S. aureus, however,
      inactivation still occurs and results demonstrate that this is unlikely to be a
      selective process. These results demonstrate that tolerance from repeated
      exposure is unlikely to occur, and further supports the potential development of
      405 nm light for clinical decontamination and treatment applications.

PMID- 29046783
TI  - Phenotypic and genotypic characteristics of ESBL and AmpC producing organisms
      associated with bacteraemia in Ho Chi Minh City, Vietnam.
AB  - BACKGROUND: Broad-spectrum antimicrobials are commonly used as empirical therapy
      for infections of presumed bacterial origin. Increasing resistance to these
      antimicrobial agents has prompted the need for alternative therapies and more
      effective surveillance. Better surveillance leads to more informed and improved
      delivery of therapeutic interventions, potentially leading to better treatment
      outcomes. METHODS: We screened 1017 Gram negative bacteria (excluding Pseudomonas
      spp. and Acinetobacter spp.) isolated between 2011 and 2013 from positive blood
      cultures for susceptibility against third generation cephalosporins, ESBL and/or
      AmpC production, and associated ESBL/AmpC genes, at the Hospital for Tropical
      Diseases in Ho Chi Minh City. RESULTS: Phenotypic screening found that 304/1017
      (30%) organisms were resistance to third generation cephalosporins; 172/1017
      (16.9%) of isolates exhibited ESBL activity, 6.2% (63/1017) had AmpC activity,
      and 0.5% (5/1017) had both ESBL and AmpC activity. E. coli and Aeromonas spp.
      were the most common organisms associated with ESBL and AmpC phenotypes,
      respectively. Nearly half of the AmpC producers harboured an ESBL gene. There was
      no significant difference (p > 0.05) between the antimicrobial resistance
      phenotypes of the organisms associated with community and hospital-acquired
      infections. CONCLUSION: AmpC and ESBL producing organisms were commonly
      associated with bloodstream infections in this setting, with antimicrobial
      resistant organisms being equally distributed between infections originating from
      the community and healthcare settings. Aeromonas spp., which was associated with
      bloodstream infections in cirrhotic/hepatitis patients, were the most abundant
      AmpC producing organism. We conclude that empirical monotherapy with third
      generation cephalosporins may not be optimum in this setting.

PMID- 29046784
TI  - The role of gene variants in the pathogenesis of neurodegenerative disorders as
      revealed by next generation sequencing studies: a review.
AB  - The clinical diagnosis of neurodegenerative disorders based on phenotype is
      difficult in heterogeneous conditions with overlapping symptoms. It does not take
      into account the disease etiology or the highly variable clinical course even
      amongst patients diagnosed with the same disorder. The advent of next generation
      sequencing (NGS) has allowed for a system-wide, unbiased approach to identify all
      gene variants in the genome simultaneously. With the plethora of new genes being
      identified, genetic rather than phenotype-based classification of Mendelian
      diseases such as spinocerebellar ataxia (SCA), hereditary spastic paraplegia
      (HSP) and Charcot-Marie-Tooth disease (CMT) has become widely accepted. It has
      also become clear that gene variants play a role in common and predominantly
      sporadic neurodegenerative diseases such as Parkinson's disease (PD) and
      amyotrophic lateral sclerosis (ALS). The observation of pleiotropy has emerged,
      with mutations in the same gene giving rise to diverse phenotypes, which further
      increases the complexity of phenotype-genotype correlation. Possible mechanisms
      of pleiotropy include different downstream effects of different mutations in the
      same gene, presence of modifier genes, and oligogenic inheritance. Future
      directions include development of bioinformatics tools and establishment of more
      extensive public genotype/phenotype databases to better distinguish deleterious
      gene variants from benign polymorphisms, translation of genetic findings into
      pathogenic mechanisms through in-vitro and in-vivo studies, and ultimately
      finding disease-modifying therapies for neurodegenerative disorders.

PMID- 29046785
TI  - Educational inequalities in premature mortality by region in the Belgian
      population in the 2000s.
AB  - BACKGROUND: In Belgium, socio-economic inequalities in mortality have long been
      described at country-level. As Belgium is a federal state with many
      responsibilities in health policies being transferred to the regional levels,
      regional breakdown of health indicators is becoming increasingly relevant for
      policy-makers, as a tool for planning and evaluation. We analyzed the educational
      disparities by region for all-cause and cause-specific premature mortality in the
      Belgian population. METHODS: Residents with Belgian nationality at birth
      registered in the census 2001 aged 25-64 were included, and followed up for 10
      years though a linkage with the cause-of-death database. The role of 3 socio
      economic variables (education, employment and housing) in explaining the regional
      mortality difference was explored through a Poisson regression. Age-standardised
      mortality rates (ASMRs) by educational level (EL), rate differences (RD), rate
      ratios (RR), and population attributable fractions (PAF) were computed in the 3
      regions of Belgium and compared with pairwise regional ratios. The global PAFs
      were also decomposed into the main causes of death. RESULTS: Regional health gaps
      are observed within each EL, with ASMRs in Brussels and Wallonia exceeding those
      of Flanders by about 50% in males and 40% in females among Belgian. Individual SE
      variables only explained up to half of the regional differences. Educational
      inequalities were also larger in Brussels and Wallonia than in Flanders, with RDs
      ratios reaching 1.8 and 1.6 for Brussels versus Flanders, and Wallonia versus
      Flanders respectively; regional ratios in relative inequalities (RRs and PAFs)
      were smaller. This pattern was observed for all-cause and most specific causes of
      premature mortality. Ranking the cause-specific PAFs revealed a higher health
      impact of inequalities in causes combining high mortality rate and relative
      inequality, with lung cancer and ischemic heart disease on top for all regions
      and both sexes. The ranking showed few regional differences. CONCLUSIONS: For the
      first time in Belgium, educational inequalities were studied by region. Among the
      Belgian, educational inequalities were higher in Brussels, followed by Wallonia
      and Flanders. The region-specific PAF decomposition, leading to a ranking of
      causes according to their population-level impact on overall inequality, is
      useful for regional policy-making processes.

PMID- 29046787
TI  - Relapsed and unresectable inflammatory myofibroblastic tumor responded to
      chemotherapy: A case report and review of the literature.
AB  - A 63-year-old female patient who had undergone cholecystectomy for inflammatory
      myofibroblastic tumor (IMT) in the gallbladder was referred to our hospital. The
      patient's disease relapsed, involving the pancreas, and was diagnosed as
      inoperable IMT 13 months after the cholecystectomy. The patient failed to respond
      to steroid and non-steroidal anti-inflammatory drug therapy, but subsequently
      exhibited a good response to vinorelbine and methotrexate combination
      chemotherapy. Little information is currently available on the efficacy of
      chemotherapy for adult-onset IMT. The present case suggests that chemotherapy
      with vinorelbine and methotrexate is a viable therapeutic option for adult
      patients with unresectable IMT.

PMID- 29046786
TI  - Sedentary time among primary school children in south-west Germany: amounts and
      correlates.
AB  - BACKGROUND: Sedentary behaviour in children is related to different health
      consequences such as overweight and cardio-metabolic diseases that can track into
      adulthood. Previous studies have shown that children spend hours being sedentary,
      but no data of sedentary time (ST) among German children has been available, yet.
      Therefore, this study investigated objectively measured amounts and correlates of
      ST in a sample of German primary school children. METHODS: Children's physical
      activity (PA) was objectively assessed for 6 days using a multi-sensor device
      (Actiheart(r); CamNtech, Cambridge, UK). Activity levels were categorized on the
      basis of energy expenditure (MET) into sedentary, light PA (LPA), and moderate to
      vigorous PA (MVPA). ST excluding sleeping hours was assessed for 231 children
      (7.1 +/- 0.6 years, male: 45.9%) and analysed for independent groups. Examined
      factors (parental education, household income, and migration background) were
      assessed by parental questionnaire. Children's weight, height and gender were
      collected in schools. Weight status was calculated on the basis of BMI
      percentiles. RESULTS: On average, children spent 3.5 +/- 1.5 h daily being
      sedentary, excluding sleeping hours. Significantly higher ST was found in girls
      (t = -4.6; p < 0.01), in children with migration background (t = -6.9; p < 0.01),
      at the weekend (t = -2.8; p < 0.01), and among inactive children (t = 6.8; p <
      0.01). Additionally, significant correlations with ST in this sample were
      identified for MVPA (B = -0.99; [-1.09;-0.88], p < 0.01), LPA (B = -0.89; [-0.97;
      0.82], p < 0.01), migration background (B = -17.64; [5.24;30.04], p < 0.01),
      gender (B = -13.48; [-25.94;-1.01], p < 0.05) and household income (B = -4.80; [
      9.07; -0.53], p < 0.05). CONCLUSION: Girls, children with migration background,
      and inactive children were identified as potential risk groups. A higher income
      was associated with less ST. In general, ST was higher at the weekend.
      Furthermore, as PA was found to be negatively correlated to ST, these activities
      may replace each other. Therefore, these findings should be considered in future
      health interventions. TRIAL REGISTRATION: German Clinical Trials Register (DRKS),
      DRKS-ID: DRKS00000494 DATE: 25/08/2010.

PMID- 29046788
TI  - A rare case of dedifferentiated liposarcoma of the sinonasal cavity: A case
      report.
AB  - Sarcoma is an uncommon histopathological presentation of sinonasal tumors,
      comprising ~15% of all cases; liposarcoma is particularly uncommon. An analysis
      of the available medical literature revealed no prior reports of dedifferentiated
      liposarcoma (DDLPS) of the sinonasal cavity. This case report presents a rare
      case of DDLPS of the sinonasal cavity. A 40-year old six-week pregnant female was
      admitted with a left nasal obstruction. Endoscopic evaluation of the left nasal
      cavity revealed a polypoid lesion. A computed tomography scan indicated a mass
      invading the left nasal cavity, maxillary sinus and anterior ethmoid sinus with
      focal destruction of the surrounding bone. A biopsy of the tumor was performed
      and hematoxylin and eosin staining of the tissue sections revealed proliferation
      of atypical and pleomorphic spindle cells with enlarged or elongated
      hyperchromatic nuclei and occasional vacuolated cytoplasm arranged in short
      interlacing fascicles or storiform structures, accompanied by tumor necrosis.
      These findings were consistent with undifferentiated pleomorphic sarcoma.
      Immunohistochemically, the tumor cells were positive for cyclin dependent kinase
      4, mouse double minute 2 homolog (MDM2) and adipophilin. Fluorescence in situ
      hybridization (FISH) analysis revealed amplification of the MDM2 gene. Recently,
      undifferentiated pleomorphic sarcoma without areas of well-differentiated
      liposarcoma but with MDM2 amplification is regarded as conventional DDLPS. In the
      present case, the tumor was diagnosed as a DDLPS due to the results of
      histopathological, immunohistochemical and FISH analysis.

PMID- 29046789
TI  - A retrospective study of late adverse events in proton beam therapy for prostate
      cancer.
AB  - The efficacy and safety of proton beam therapy (PBT) were retrospectively
      evaluated in 111 consecutive patients with prostate cancer who underwent
      definitive PBT between 2008 and 2012. Following exclusion of 18 patients due to
      treatment suspension, loss to follow-up, and histology, the analysis included 93
      patients with a median age of 68 years (range, 49-81 years). A total of 7, 32 and
      54 prostate cancer patients were classified as low-, intermediate- and high-risk,
      respectively, as follows: High-risk, T>=3a or prostate-specific antigen (PSA)
      >=20 ng/ml or Gleason Score >=8; low-risk, T <=2b and PSA<=10 ng/ml and Gleason
      Score=6; intermediate-risk, all other combinations. The median initial prostate
      specific antigen (PSA) level was 9.75 ng/ml (range, 1.4-100 ng/ml) and the median
      Gleason score was 7 (range, 6-10). Patients with low-risk disease received 74 GyE
      (relative biological effectiveness=1.1) in 37 fractions, and those at
      intermediate or higher risk received 78 GyE in 39 fractions. Complete androgen
      blockade (CAB) therapy was performed from 6 months prior to PBT for patients with
      intermediate- or high-risk disease. CAB was continued during PBT and then
      terminated at the end of PBT for intermediate-risk patients. Patients at high
      risk continued CAB for 3 years. No combination therapy was used for low-risk
      patients. All the patients were followed up for >2 years after PBT, and all but
      one were PSA failure-free. The Common Terminology Criteria for Adverse Events
      v.4.0 was used to evaluate late adverse events. One patient developed grade 3 non
      infectious cystitis and hematuria. Grade 2 urinary frequency was observed in 1
      patient, and grade 2 rectal bleeding occurred in 4 patients. Of the 4 patients
      with grade 2 rectal bleeding, 2 received anticoagulant therapy, but none had
      diabetes mellitus or another high-risk comorbidity. The median time to occurrence
      of an adverse event of grade >=2 was 14 months (range, 3-41 months). Therefore,
      the present retrospective study revealed that PBT at 78 GyE/39 Fr was well
      tolerated and achieved good tumor control in patients with prostate cancer.

PMID- 29046790
TI  - Intraluminal rectal cancer metastasis to the small bowel: An extremely rare case
      report.
AB  - Prolonged survival in patients suffering from colorectal cancer (CRC) may lead to
      the emergence of rare metastatic sites that are not well-documented in the
      literature. We herein describe a very rare case of an intraluminal small
      intestinal metastasis in a patient with previously resected CRC. A 71-year-old
      Caucasian male patient with a history of rectosigmoid junction cancer was
      initially treated with anterior resection. The tumor was classified as pT3pN0
      (0/26) M0, stage II. Eighteen months after the primary surgery, local recurrence
      was detected in the presacral region, and the patient received combined image
      guided radiotherapy and chemotherapy. Two months later, due to residual disease
      at the level of the anastomosis, the patient underwent additional low anterior
      resection with a diverting stoma. During extensive adhesiolysis, a small palpable
      intraluminal mass was identified in the jejunum, and segmental small bowel
      resection was performed. Pathological examination of the resected specimen
      confirmed that the lesion was a metastasis from the CRC primary. The precise
      mechanism and clinical significance of CRC metastasis to the small bowel remain
      unclear. There is limited clinical experience with this condition, as <20 cases
      have been reported in the literature to date. The main symptoms leading to
      evaluation, diagnosis and surgical resection are bowel obstruction and bleeding.
      The present case highlights the possibility of uncomplicated presence of
      metastatic CRC in the small bowel. Therefore, dilligent inspection of the
      peritoneal cavity, including the entire length of the gastrointestinal canal, is
      of paramount importance, particularly in cases of recurrent CRC.

PMID- 29046791
TI  - Evaluation of safety, feasibility and the long-term outcomes of colorectomy for
      colorectal adenocarcinoma in patients older than 80 years of age.
AB  - The short- and long-term outcomes of colorectomy for colorectal adenocarcinoma
      have not been fully evaluated in elderly patients. The present retrospective
      study investigated patients who underwent curative surgery for colorectal cancer
      at the Department of Surgery, Yokohama City University (Yokohoma, Japan). The
      patients were categorized into two groups: Elderly patients (70-79 years of age;
      group A) and extremely elderly patients (>=80 years of age; group B). The rates
      of surgical morbidity, surgical mortality, overall survival (OS), and recurrence
      free survival (RFS) in the two groups were compared. A total of 191 patients were
      evaluated in the current study. Of these, 137 patients were included in group A,
      and 54 were included in group B. With the exception of the American Society of
      Anesthesiology physical status score, there were no significant differences in
      the preoperative clinicopathological outcomes of the two groups. The overall
      complication rates in groups A and B were 12.4 and 16.7%, respectively, and did
      not differ to a statistically significant extent (P=0.440). In addition, surgical
      mortality was not observed in either group. The 5-year OS and RFS rates were
      similar between the group A and B patients (75.6 vs. 76.9%; P=0.5537; and 71.9
      vs. 62.2%; P=0.192, respectively). The short-term outcomes and long-term survival
      following colorectomy for colorectal adenocarcinoma among patients in the 70-79
      years of age group, and those who were >=80 in the current study were almost
      equal. Thus, it is not necessary to avoid colorectomy for colorectal
      adenocarcinoma in elderly patients simply because of their age.

PMID- 29046793
TI  - Updated recommendation on molecular-targeted therapy for metastatic renal cell
      cancer.
AB  - Molecular-targeted therapy was recommended for the systemic therapy of renal cell
      cancer (RCC) in the RCC guidelines, but these guidelines do not address the order
      of administration of the multiple presently available agents. There are several
      aspects that remain unknown regarding the optimal administration order and
      combination of molecular-targeted drugs. Until the optimal treatment sequence is
      determined by clinical trials, treatment individualization is required for each
      patient based on patient and disease characteristics. We herein investigate 12
      cases of RCC patients who received axitinib. Axitinib was used as the first-line
      drug in 4 cases, second-line in 5 cases, third-line in 1 case and as a fourth
      line drug in 2 cases. Partial response (PR) was observed in 4 cases (30%) and
      stable disease in 4 cases (30%) during axitinib treatment, with an overall
      response rate of 60%. The duration of PR ranged from 6 to 19 months. Based on our
      cases, axitinib exhibited reasonable therapeutic efficacy as first- as well as
      second-line treatment. However, more cases are required to draw firm conclusions.

PMID- 29046794
TI  - Palliative surgery for giant mucinous carcinoma of the breast in an elderly
      patient: A rare case report.
AB  - Mucinous breast carcinoma (MBC) is relatively rare, accounting for <10% of all
      breast cancers in women. These tumors are usually slow-growing and exhibit less
      aggressive characteristics compared with other types of breast cancer. Between
      1989 and 2016, 55 patients underwent surgery for MBC at the Shiga Medical Center
      for Adults (Moriyama, Japan). The 10-year disease-free survival (DFS) and overall
      survival rates were 94.5 and 100.0%, respectively. Specifically, the 10-year DFS
      rates of pure MBC (PMBC) and mixed MBC were 97.7 and 83.3%, respectively. We
      herein report the case of a sizeable mucinous carcinoma causing rupture of the
      skin and bleeding due to tumor pressure. Palliative surgery was performed in
      order to remove the bleeding source after a total of 5 months of preoperative
      endocrine-based therapy. In conclusion, palliative surgery improved the patient's
      quality of life and may be a viable option for PMBC patients. The aim of the
      present study was to review the characteristics and management of these tumors,
      particularly in elderly patients.

PMID- 29046792
TI  - There is no relationship between SOD2 Val-16Ala polymorphism and breast cancer
      risk or survival.
AB  - Breast cancer is the most common diagnosed cancer among females worldwide.
      Superoxide dismutase 2 (SOD2), an antioxidant enzyme, may break the balance
      between the oxidant and antioxidant system to induce various diseases. The
      present study aimed to clarify the association between the SOD2 Val-16Ala
      polymorphism and breast cancer risk or survival. Thus, a meta-analysis of the
      relevant articles retrieved from PubMed and EMBASE databases was conducted to
      illuminate the association with odd ratios (ORs) or hazards ratios (HRs). A total
      of 26 eligible publications (n=38,008) were available in risk analysis and eight
      publications (n=5,746) in survival analysis. The results demonstrated a marginal
      association between breast cancer risk and SOD2 polymorphism in Caucasian
      patients [TT vs. CT + CC: (OR, 0.94; 95% confidence interval (CI), 0.88-1.00)].
      However, no other positive results were observed in risk and survival of breast
      cancer in the whole study [T vs. C: (OR, 0.99; 95% CI, 0.96-1.02); CT vs. CC:
      (OR, 1.00; 95% CI, 0.95-1.05); TT vs. CC: (OR, 0.98; 95% CI, 0.92-1.05); TT vs.
      CT + CC: (OR, 1.00; 95% CI, 0.95-1.05); CT + TT vs. CC: (OR, 0.99; 95% CI, 0.95
      1.05)]. The present meta-analysis indicated that there was no significant
      relationship between SOD2 Val-16Ala polymorphism and breast cancer risk or
      survival, although in Caucasian patients, the SOD2 TT genotype may marginally
      decrease the risk of breast cancer in comparison to the CT + CC genotype.

PMID- 29046795
TI  - Comparison of clinicopathological characteristics between cirrhotic and non
      cirrhotic patients with intrahepatic cholangiocarcinoma: A large-scale
      retrospective study.
AB  - The effect of cirrhosis on the characteristics of intrahepatic cholangiocarcinoma
      (ICC) has not been fully elucidated. The purpose of this study was to investigate
      how cirrhosis affects the clinicopathological characteristics and survival of
      surgically treated ICC patients. A total of 1,312 ICC patients surgically treated
      between January 2007 and December 2011 at a single institution were
      retrospectively reviewed and the clinicopathological data were compared between
      cirrhotic and non-cirrhotic patients. Univariate and multivariate analyses were
      performed to identify significant and independent prognostic factors in this
      cohort. A total of 302 patients (23.0%) were cirrhotic. Compared with cirrhotic
      patients, the tumors in non-cirrhotic patients were usually larger, less
      differentiated, and more likely to have lymphatic metastasis, vascular and
      perineural invasion. Following resection, cirrhotic patients achieved a longer
      survival compared with non-cirrhotic patients (16.0 vs. 13.0 months,
      respectively; P<0.038). Multivariate analysis demonstrated that hepatitis B virus
      infection and cirrhosis were independent favorable prognostic factors, while the
      presence of cholelithiasis, elevated carbohydrate antigen 19-9 and
      carcinoembryonic antigen levels, multiple tumors, lymphatic metastasis, vascular
      invasion and positive surgical margin status were independent unfavorable
      prognostic factors. Overall, the clinicopathological characteristics of ICC
      patients with and without cirrhosis differed significantly. Compared with
      cirrhotic patients, in whom the biological behavior of ICC was similar to that of
      HCC, non-cirrhotic patients exhibited higher-risk pathological characteristics,
      lower curative resection rate and worse survival.

PMID- 29046796
TI  - Pulmonary and pleural metastasis of intracranial anaplastic meningioma in a 3
      year-old boy: A case report.
AB  - In adults, meningiomas occasionally display aggressive behavior and may
      occasionally metastasize. By contrast, pediatric meningiomas are rare, and there
      is limited information regarding their clinical characteristics, treatment and
      prognosis. We herein report the case of a 3-year-old boy with anaplastic
      meningioma with a history of local recurrence and late pulmonary metastasis. At
      diagnosis, a 70-mm mass lesion in was identified in the right frontal lobe, with
      intratumoral hemorrhage. The tumor was attached to the falx cerebri and was
      completely resected. The histological diagnosis was anaplastic meningioma, World
      Health Organization grade III. Two months after the surgery, the meningioma
      recurred at the same site. Although the patient received radiotherapy after a
      second operation, the tumor metastasized to the lung and pleura 8 months after
      the initial operation. The metastasis was resistant to treatment, even after
      gross total resection, and the effectiveness of further radiotherapy was limited.
      The patient succumbed to the disease 1 year and 4 months after the initial
      diagnosis. The findings of the present case and a review of the relevant
      literature suggest that recurrence and metastasis of meningiomas are difficult to
      predict. Therefore, such patients should be carefully monitored throughout the
      follow-up period.

PMID- 29046797
TI  - Gastrointestinal tract-like muscular walls in ovarian mature cystic teratomas: A
      histopathological study.
AB  - To elucidate the frequency and histopathological features of gastrointestinal
      (GI) tract-like muscular walls developing in ovarian mature cystic teratoma
      (MCT), the present study examined 149 MCTs surgically removed from 126 females,
      including 23 bilateral cases. GI tract-like muscular walls were identified in 9
      (7.1%) cases, and were accompanied by mucosa in 5 cases, muscularis mucosae in 5
      cases, serosa in 5 cases and all of these components in 3 cases. The mean size of
      the GI tract-like structures was 0.6 cm. The presence of MCT-related GI tract
      like muscular walls was not significantly associated with patient age, size of
      MCTs or bilateral presence of MCT. The detected mucosae and muscular walls
      commonly demonstrated incomplete or anomalous features. Immunohistochemically, a
      few weakly KIT+ spindle and/or stellate cells were identified in 7 cases (77.8%
      of the 9 cases of MCT-related GI tracts); these cells were presented chiefly near
      conspicuous or inconspicuous S-100 protein+ neural tissues between the
      conspicuous or inconspicuous two muscular wall layers, indicating interstitial
      cells of Cajal (ICCs). Discovered on gastrointestinal stromal tumors 1 co
      expression in KIT+ ICCs was observed in only 1 case. Neural cell-related
      intramuscular cluster of differentiation 34+ cells were occasionally observed;
      however, no hyperplastic ICCs were observed in the present study.

PMID- 29046798
TI  - Monitoring of recurrent and superior laryngeal nerve function using an
      AirwayscopeTM during thyroid surgery.
AB  - In thyroid surgery, intraoperative identification and preservation of the
      recurrent laryngeal nerve (RLN) and superior laryngeal nerve external branch
      (SLNEB) are crucial. Several reports have proposed that electromyography (EMG)
      monitoring is an acceptable adjunct for identification and preservation of the
      RLN. However, a limited number of hospitals have access to an EMG monitoring
      system. Therefore, the development of another viable monitoring method is
      required. The aim of the present study was to design a new RLN and SLNEB
      monitoring method combining an AirwayscopeTM (AWS) and a facial nerve stimulator.
      The facial nerve-stimulating electrode stimulates the RLN or SLNEB, so that the
      movement of the vocal cord may be observed with an AWS. This monitoring method
      was performed on 10 patients with a thyroid tumor. In all the cases, RLN and
      SLNEB were identified and vocal cord function was preserved. All the patients
      exhibited normal vocal cord function following surgery. Thus, the new RLN and
      SLNEB monitoring method using an AWS and a facial nerve stimulator is useful in
      thyroid surgery, and this method may be used as a reliable and available
      alternative to EMG monitoring to ensure the normal function of the vocal cord.

PMID- 29046799
TI  - Retrospective analysis of acute exacerbation of interstitial lung diseases with
      nanoparticle albumin-bound paclitaxel in patients with advanced lung cancer with
      preexisting interstitial lung disease.
AB  - Lung cancer with preexisting interstitial lung disease (ILD) is difficult to
      treat due to the risk of acute exacerbation of ILD. Nanoparticle albumin-bound
      (nab-) paclitaxel improves the overall response rate and reduces neuropathy more
      efficiently compared with conventional solvent-based (sb-) paclitaxel in patients
      with advanced non-small-cell lung cancer. However, it is not known whether the
      risk of acute exacerbation of ILD with nab-paclitaxel is higher compared with
      that with sb-paclitaxel. Advanced lung cancer patients with ILD treated with nab
      paclitaxel (n=14) or sb-paclitaxel (n=14) were retrospectively reviewed. Acute
      exacerbation of ILD developed in 1/14 patients (7.7%) receiving nab-paclitaxel
      and 3/14 patients (21.4%) receiving sb-paclitaxel; the difference was not
      statistically significant. To the best of our knowledge, this is the first study
      to compare the incidence of acute exacerbation of ILD with nab-paclitaxel with
      that of sb-paclitaxel in patients with advanced lung cancer with preexisting ILD.
      The results of the present study support conducting a prospective clinical trial
      to confirm the clinical benefit of this agent.

PMID- 29046800
TI  - Re-irradiation of locoregional esophageal cancer recurrence following definitive
      chemoradiotherapy: A report of 6 cases.
AB  - There is currently no consensus on salvage therapy for recurrent esophageal
      cancer. Salvage surgery is a well-established option for attaining long-term
      survival; however, it is associated with a high risk of perioperative morbidity
      and mortality. A total of 6 patients who underwent re-irradiation for recurrence
      of locoregional esophageal cancer following definitive chemoradiotherapy were
      investigated. The median interval between initial radiotherapy and re-irradiation
      was 17.4 months (range, 6.4-59.2 months). Re-irradiation salvage therapy was
      mostly administered with concurrent chemotherapy, which consisted of several
      cycles of nedaplatin on day 1 and oral S-1 administration on days 1-14. The
      median survival after re-irradiation was 13.6 months (range, 1.9-33.3 months). A
      total of 3 patients who completed hyperfractionated radiation therapy survived
      for >1 year. One patient has had no signs of recurrence or late radiation
      toxicity for >2 years. Severe acute hematological adverse events (AEs) occurred
      in 3 patients, including 1 case of grade 4 leukopenia. One severe late AE
      occurred in 1 patient, who developed grade 3 dysphagia and became permanently
      dependent on percutaneous endoscopic gastrostomy tube feeding. Salvage
      radiotherapy is considered to be a good treatment option for inoperable
      locoregional recurrent esophageal cancer. The results of the present study
      demonstrated that re-irradiation, with or without chemotherapy, for recurrent
      esophageal carcinoma after definitive chemoradiotherapy was tolerable and yielded
      reasonably satisfactory results.

PMID- 29046801
TI  - Outcome of decompression using a transnasal ileus tube in malignant adhesive
      bowel obstruction: A retrospective study.
AB  - Malignant adhesive bowel obstruction caused by peritoneal carcinomatosis is a
      common complication of advanced abdominal malignancies, and surgical treatment
      provides little benefit. The present study was undertaken to evaluate the
      decompression efficacy of a transnasal ileus tube under X-ray guidance, with
      benign adhesive bowel obstruction patients serving as the control group. A total
      of 21 patients with malignant adhesive bowel obstruction and 60 patients with
      benign conditions were enrolled between February 2011 and March 2015. All the
      patients were treated with transnasal ileus intubation under X-ray guidance. A
      total of 9 of the 21 malignant cases and 44 of the 60 benign cases were
      successfully treated with transnasal ileus intubation (42.9 vs. 73.3%,
      respectively; P=0.01). Treatment in 8 malignant and 4 benign cases failed due to
      death, tube discharge, and/or therapy abandonment, all of which contributed to a
      significant difference between the two groups (38.1 vs. 6.7%, respectively;
      P=0.01). A total of 4 malignant cases and 12 benign adhesion cases received
      further surgical treatment, the success rate of which was 50 vs. 91.7%,
      respectively. The rate of successfully treated intubation cases in all resolution
      patients was similar between the two groups (81.8% in the malignant group and 80%
      in the benign group; P=0.89). In conclusion, ileus tube decompression in patients
      with malignant conditions was associated with a lower success rate and lower
      further surgical intervention success rate compared with that observed in
      patients with benign conditions. However, insertion of an ileus tube may
      successfully cure ~80% of all resolution patients in both groups; thus, it may be
      used as a feasible therapy in malignant adhesive bowel obstruction patients,
      similar to patients with benign obstruction.

PMID- 29046802
TI  - Tuberous sclerosis-associated renal angiomyolipoma: A report of two cases and
      review of the literature.
AB  - In the general population, tuberous sclerosis-associated renal angiomyolipoma
      (RAML) is a rare benign hamartoma with potentially life-threatening complications
      and a poor prognosis. The two patients reported in the present study, who were
      diagnosed with bilateral RAML and spontaneous rupture of the RAML with tuberous
      sclerosis, presented with flank pain, abdominal pain, hemorrhage, hematuria and
      multiple lesions. The two cases are representative examples of the disease, and
      highlight the importance of determining the risk of acute hemorrhage in the early
      stages, and the significance of timely and proper treatment.

PMID- 29046803
TI  - Antitumor activity of yulangsan polysacchrides in mice bearing S180 sarcoma
      tumors.
AB  - Sarcoma is one of the most prevalent pediatric tumors and the therapeutic role of
      chemotherapy has yet to be elucidated. It has been reported that extracts of
      Longyanshen (Yulangsan) may enhance the sensitivity of drug-resistant cancer cell
      lines, and improve the immune dysfunction induced by cyclophosphamide (CTX) in
      mice. The present in vivo study investigated the antitumor effects of Yulangsan
      polysaccharides (YLSPS) and their interaction with CTX in murine sarcoma 180
      (S180)-bearing mice. Immunohistochemistry was used to detect the expression of
      apoptosis-related proteins. The ultrastructure of sarcoma cells was examined by
      transmission electron microscopy and the tumor growth rate was determined by
      measuring the tumor weight. A dose-dependent inhibition of sarcoma growth was
      observed in S180-bearing mice following administration of YLSPS. In combination
      with CTX, an additive antitumor effect was obtained, which was accompanied by
      amelioration of immune function. YLSPS also potentiated the tumor suppression
      effect of CTX while avoiding cytotoxicity against immune cells. YLSPS inhibited
      sarcoma growth in S180-bearing mice through the induction of apoptosis in S180
      sarcoma cells. YLSPS also attenuated CTX-induced cytotoxicity to the immune
      system while potentiating the tumor suppression effect. These results provide
      additional information regarding combination therapy with YLSPS and chemotherapy
      for the treatment of sarcoma.

PMID- 29046804
TI  - Sport practice, physical structure, and body image among university students.
AB  - BACKGROUND: The aim of this study was to estimate body image perception in
      undergraduate students, and to investigate its associations with weight status,
      abdominal obesity, muscularity, gender and sport. METHODS: The sample consisted
      of 231 Italian students (174 males and 57 females); anthropometric measurements,
      taken by trained technicians, were: height, weight, arm-circumference, waist and
      hip circumferences. BMI, WHR and Delta arm-circumference were calculated. Body
      image was assessed using body silhouette charts. Information about sport
      (currently practiced sport, starting age, and weekly hours of sport) was acquired
      with questionnaires. RESULTS: Females perceived themselves as slightly
      overweight, while males identified themselves as normal weight. Females had a
      tendency to desire to be thinner in all weight status categories; in males,
      normal weight subjects had a tendency to desire to be larger, while overweight
      wished to be thinner. Sport practice was significantly higher in males.
      Individuals who were overweight and did less sport were significantly more likely
      to have higher body dissatisfaction. CONCLUSIONS: The present study highlights a
      positive relationship between sport practice, corpulence and body image
      perception.

PMID- 29046805
TI  - Reprogrammable ultra-fast shape-transformation of macroporous composite hydrogel
      sheets.
AB  - In this communication, we report a composite macroporous hydrogel sheet that can
      rapidly transform into multiple 3D shapes in response to near-infrared (NIR)
      light on demand. The transformation relies on the photo-thermal-induced
      asymmetric shrinking of the hydrogel material, which is further verified by
      finite element modeling.

PMID- 29046806
TI  - Development of a fully automated chemiluminescence immunoassay for urine
      monomeric laminin-gamma2 as a promising diagnostic tool of non-muscle invasive
      bladder cancer.
AB  - BACKGROUND: Monomeric laminin-gamma2 in urine is a potential biomarker for
      bladder cancer. However, the current detection system uses an antibody that
      cannot discriminate between monomeric laminin-gamma2 and the heterotrimeric
      gamma2 chain of laminin-332, which may cause false-positive reactions. The
      present study aimed to develop a fully automated chemiluminescence immunoassay
      system using a specific monoclonal antibody against monomeric laminin-gamma2.
      METHODS: In total, 237 urine specimens (84 from patients with bladder cancer, 48
      from patients with benign urological disease, and 105 from healthy donors) were
      collected, and monomeric laminin-gamma2 values in the urine were measured using a
      fully automated chemiluminescence immunoassay. RESULTS: The results revealed that
      laminin-gamma2 values in patients with benign urological disease were comparable
      to those of healthy donors and that the chemiluminescence immunoassay's lower
      limit of detection was 10 pg/mL (approximately 20-fold better than the sandwich
      enzyme-linked immunosorbent assay's limit of 200 pg/mL). Moreover, the
      chemiluminescence immunoassay demonstrated that patients with bladder cancer,
      including non-muscle invasive bladder cancer (<=pT1), had higher laminin-gamma2
      values than patients with benign urological disease or healthy donors.
      CONCLUSIONS: These results suggest that urine monomeric laminin-gamma2 may be a
      promising biomarker to diagnose cases of non-muscle invasive bladder cancer using
      a fully automated chemiluminescence immunoassay system.

PMID- 29046807
TI  - Pulmonary schistosomiasis mimicking IgG4-related lung disease.
AB  - IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease
      characterized by tumefactive lesions in various organ systems, including the
      lungs. Clinical and radiological manifestations of IgG4-RD are relatively non
      specific, and we report a case highlighting the importance of histopathological
      confirmation in cases of suspected IgG4-related lung disease. A 44-year-old male
      with significantly elevated serum IgG4 levels, patchy consolidation on thoracic
      CT imaging, and cough was referred with suspected IgG4-related lung disease.
      However, surgical lung biopsy revealed an unexpected diagnosis of pulmonary
      schistosomiasis, and following treatment with praziquantel, cough resolved and
      IgG4 levels significantly declined. This case highlights the potentially diverse
      array of conditions that may mimic IgG4-related lung disease and the importance
      of comprehensive evaluation including histopathological confirmation where
      possible.

PMID- 29046809
TI  - Hospital resuscitation teams: a review of the risks to the healthcare worker.
AB  - BACKGROUND: "Code blue" events and related resuscitation efforts involve
      multidisciplinary bedside teams that implement specialized interventions aimed at
      patient revival. Activities include performing effective chest compressions,
      assessing and restoring a perfusing cardiac rhythm, stabilizing the airway, and
      treating the underlying cause of the arrest. While the existing critical care
      literature has appropriately focused on the patient, there has been a dearth of
      information discussing the various stresses to the healthcare team. This review
      summarizes the available literature regarding occupational risks to medical
      emergency teams, characterizes these risks, offers preventive strategies to
      healthcare workers, and highlights further research needs. METHODS: We performed
      a literature search of PubMed for English articles of all types (randomized
      controlled trials, case-control and cohort studies, case reports and series,
      editorials and commentaries) through September 22, 2016, discussing potential
      occupational hazards during resuscitation scenarios. Of the 6266 articles
      reviewed, 73 relevant articles were included. RESULTS: The literature search
      identified six potential occupational risk categories to members of the
      resuscitation team-infectious, electrical, musculoskeletal, chemical,
      irradiative, and psychological. Retrieved articles were reviewed in detail by the
      authors. CONCLUSION: Overall, we found there is limited evidence detailing the
      risks to healthcare workers performing resuscitation. We identify these risks and
      offer potential solutions. There are clearly numerous opportunities for further
      study in this field.

PMID- 29046808
TI  - Occurrence and reproductive roles of hormones in seminal plasma.
AB  - Only 2-5% of seminal fluid is composed of spermatozoa, while the rest is seminal
      plasma. The seminal plasma is a rich cocktail of organic and inorganic compounds
      including hormones, serving as a source of nutrients for sperm development and
      maturation, protecting them from infection and enabling them to overcome the
      immunological and chemical environment of the female reproductive tract. In this
      review, a survey of the hormones found in human seminal plasma, with particular
      emphasis on reproductive hormones is provided. Their participation in
      fertilization is discussed including their indispensable role in ovum
      fertilization. The origin of individual hormones found in seminal plasma is
      discussed, along with differences in the concentrations in seminal plasma and
      blood plasma. A part of review is devoted to methods of measurement, emphasising
      particular instances in which they differ from measurement in blood plasma. These
      methods include separation techniques, overcoming the matrix effect and current
      ways for end-point measurement, focusing on so called hyphenated techniques as a
      combination of chromatographic separation and mass spectrometry. Finally, the
      informative value of their determination as markers of male fertility disorders
      (impaired spermatogenesis, abnormal sperm parameters, varicocele) is discussed,
      along with instances where measuring their levels in seminal plasma is preferable
      to measurement of levels in blood plasma.

PMID- 29046810
TI  - Competency in supportive supervision: a study of public sector medicines
      management supervisors in Uganda.
AB  - BACKGROUND: Supportive supervision has been found to be more effective than
      corrective fault-oriented inspections. Uganda's Ministry of Health in 2012
      implemented a comprehensive strategy (SPARS) to build medicines management
      capacity in public sector health facilities. The approach includes supportive
      supervision. This structured observational study assesses supportive supervision
      competency among medicines management supervisors (MMS). METHOD: The study used
      structured observations of two groups of five purposely selected MMS-one group
      supervising facilities with greater medicines management improvement during one
      year of SPARS and one group with less improvement, based on quantitative metrics.
      We observed and scored behaviors and skills of supervisors in 11 categories
      deemed critical for effective and supportive supervision. RESULTS: Supportive
      supervision was not evenly or adequately implemented, with the median supportive
      supervision competency score for all observed supervisors being 38%. Supervisors'
      main strengths were problem identification, data interpretation, education, and
      providing constructive feedback (45%-47%). Their weakest areas were assuring
      continuity and setting targets (17%), and most MMS were fair to strong in
      effective communication, use of tools, and problem solving. MMS of facilities
      with little improvement in medicines management over time were weak in setting
      targets and promoting participation. There was a 33 percentage point difference
      in the median supportive supervision competency scores between MMS of facilities
      with more versus less improvement (57%-24%) and a 77 percentage point difference
      in competency between the highest and lowest scoring MMS (77%-0%). We did not
      find a relationship between MMS experience (number of visits implemented) and
      their supportive supervision competency or facility improvement in medicines
      management. However, there is a likely relationship between supportive
      supervision competency and facility improvement. CONCLUSION: Competency of MMS in
      supportive supervision among the sampled MMS was generally weak, but with much
      individual variation. Our results suggest that MMS' supportive supervision
      competency is positively related to the SPARS effectiveness scores of the
      facilities they supervise. We recommend strategies to strengthen supportive
      supervision behaviors and skills.

PMID- 29046811
TI  - Association between supervisors' behavior and wage workers' job stress in Korea:
      analysis of the fourth Korean working conditions survey.
AB  - BACKGROUND: In modern society, many workers are stressed. Supervisors' support or
      behavior can affect the emotional or psychological part of the worker. The
      purpose of this study is to investigate the effect of supervisor's behavior on
      worker's stress. METHODS: The study included 19,272 subjects following the
      assignment of weighted values to workers other than soldiers using data from the
      Fourth Korean Working Condition Survey. Supervisors' behavior was measured using
      5 items: "supervisor feedback regarding work," "respectful attitude," "good
      conflict-resolution ability," "good work-related planning and organizational
      ability," and the encouragement of participation in important decision making.
      Job stress was measured using 1 item: "I experience stress at work." Multiple
      logistic regression analysis was performed to examine the effects of supervisors'
      behavioral, general, occupational, and psychosocial characteristics on job stress
      in workers. Organizational characteristics associated with supervisors' behavior
      were also analyzed. RESULTS: The results showed that supervisors' provision of
      feedback regarding work increased workers' job stress (OR = 1.329, 95% CI = 1.203
      ~ 1.468). When a supervisor respect workers (OR = 0.812, 95% CI = 0.722 ~ 0.913)
      or good at planning and organizing works (OR = 0.816, 95% CI: 0.732 ~ 0.910),
      workers' job stress decreased. In particular, the two types of supervisor
      behaviors, other than feedback regarding work, were high in private-sector
      organizations employing less than 300 employees. CONCLUSION: Supervisors'
      behavior influenced job stress levels in workers. Therefore, it is necessary to
      increase education regarding the effects of supervisors' behavior on job stress,
      which should initially be provided in private-sector organizations with up to 300
      employees.

PMID- 29046812
TI  - Relationship of activities outside work to sleep and depression/anxiety disorders
      in Korean workers: the 4th Korean working condition survey.
AB  - BACKGROUND: Sleep disorders and depression/anxiety disorders are long-standing
      and significant problem for mental health. Also there are already known so many
      negative health effect of these disorders. But there were few studies to examine
      the association between activities outside work and forementioned disorders. So
      this study aimed the association of those things by using the Republic of Korean
      data. METHODS: Data from 32,232 wage workers were used in the 4th Korean Working
      Condition Survey. General and occupational characteristics, sleep disorders,
      depression/anxiety disorders and activities outside work are included in
      questionnaire. To find the relationship between activities outside work and
      sleep, depression/anxiety disorders, multivariate logistic regression analysis
      was used after adjusting for general and occupational characteristics. RESULTS:
      We observed that volunteer activities increased the odds ratio of both sleep
      disorders and depression/anxiety disorders(Odds ratio[OR] = 1.35, 95% confidence
      interval[CI]: 1.03-1.78 and OR = 1.54, 95% CI: 1.29-1.84, respectively). And self
      development activities increase the odds ratio of sleep disorders(OR = 1.35, 95%
      CI: 1.17-1.57). Gardening activities lowered the odds ratio of depression/anxiety
      disorders(OR = 0.74, 95% CI: 0.59-0.94). CONCLUSION: Some of activities outside
      work were related to sleep disorders and depression/anxiety disorders among
      Korean wage workers. Our results showed negative health effect of some kinds of
      activities outside work such as volunteering and self-devlopment compared to
      other studies that emphasized positive effect of those activities for health.

PMID- 29046813
TI  - Single nucleotide polymorphisms and microsatellites in the canine glutathione S
      transferase pi 1 (GSTP1) gene promoter.
AB  - BACKGROUND: Genetic polymorphisms within the glutathione S-transferase P1 (GSTP1)
      gene affect the elimination of toxic xenobiotics by the GSTP1 enzyme. In dogs,
      exposure to environmental chemicals that may be GSTP1 substrates is associated
      with cancer. The objectives of this study were to investigate the genetic
      variability in the GSTP1 promoter in a diverse population of 278 purebred dogs,
      compare the incidence of any variants found between breeds, and predict their
      effects on gene expression. To provide information on ancestral alleles, a number
      of wolves, coyotes, and foxes were also sequenced. RESULTS: Fifteen single
      nucleotide polymorphisms (SNPs) and two microsatellites were discovered. Three of
      these loci were only polymorphic in dogs while three other SNPs were unique to
      wolves and coyotes. The major allele at c.-46 is T in dogs but is C in the wild
      canids. The c.-185 delT variant was unique to dogs. The microsatellite located in
      the 5' untranslated region (5'UTR) was a highly polymorphic GCC tandem repeat,
      consisting of simple and compound alleles that varied in size from 10 to 22
      repeat units. The most common alleles consisted of 11, 16, and 17-repeats. The 11
      repeat allele was found in 10% of dogs but not in the other canids. Unequal
      recombination and replication slippage between similar and distinct alleles may
      be the mechanism for the multiple microsatellites observed. Twenty-eight
      haplotypes were constructed in the dog, and an additional 8 were observed in
      wolves and coyotes. While the most common haplotype acrossbreeds was the wild
      type *1A(17), other prevalent haplotypes included *3A(11) in Greyhounds, *6A(16)
      in Labrador Retrievers, *9A(16) in Golden Retrievers, and *8A(19) in Standard
      Poodles. Boxers and Siberian Huskies exhibited minimal haplotypic diversity.
      Compared to the simple 16*1 allele, the compound 16*2 allele (found in 12% of
      dogs) may interfere with transcription factor binding and/or the stability of the
      GSTP1 transcript. CONCLUSIONS: Dogs and other canids exhibit extensive variation
      in the GSTP1 promoter. Genetic polymorphisms within distinct haplotypes prevalent
      in certain breeds can affect GSTP1 expression and carcinogen detoxification, and
      thus may be useful as genetic markers for cancer in dogs.

PMID- 29046814
TI  - Emergence and loss of spliceosomal twin introns.
AB  - BACKGROUND: In the primary transcript of nuclear genes, coding sequences-exons
      usually alternate with non-coding sequences-introns. In the evolution of
      spliceosomal intron-exon structure, extant intron positions can be abandoned and
      new intron positions can be occupied. Spliceosomal twin introns ("stwintrons")
      are unconventional intervening sequences where a standard "internal" intron
      interrupts a canonical splicing motif of a second, "external" intron. The
      availability of genome sequences of more than a thousand species of fungi
      provides a unique opportunity to study spliceosomal intron evolution throughout a
      whole kingdom by means of molecular phylogenetics. RESULTS: A new stwintron was
      encountered in Aspergillus nidulans and Aspergillus niger. It is present across
      three classes of Leotiomyceta in the transcript of a well-conserved gene encoding
      a putative lipase (lipS). It occupies the same position as a standard intron in
      the orthologue gene in species of the early divergent classes of the
      Pezizomycetes and the Orbiliomycetes, suggesting that an internal intron has
      appeared within a pre-extant intron. On the other hand, the stwintron has been
      lost from certain taxa in Leotiomycetes and Eurotiomycetes at several occasions,
      most likely by a mechanism involving reverse transcription and homologous
      recombination. Another ancient stwintron present across whole Pezizomycotina
      orders-in the transcript of the bifunctional biotin biosynthesis gene bioDA
      occurs at the same position as a standard intron in many species of non-Dikarya.
      Nevertheless, also the bioDA stwintron has disappeared from certain lineages
      within the taxa where it occurs, i.e., Sordariomycetes and Botryosphaeriales.
      Intriguingly, only the internal intron was lost from the Sordariomycetes bioDA
      stwintron at all but one occasion, leaving a standard intron in the same
      position, while where the putative lipase stwintron was lost, no intronic
      sequences remain. CONCLUSIONS: Molecular phylogeny of the peptide product was
      used to monitor the existence and fate of a stwintron in the transcripts of two
      neatly defined fungal genes, encoding well conserved proteins. Both defining
      events-stwintron emergence and loss-can be explained with extant models for
      intron insertion and loss. We thus demonstrate that stwintrons can serve as model
      systems to study spliceosomal intron evolution.

PMID- 29046815
TI  - Non adherence to inhalational medications and associated factors among patients
      with asthma in a referral hospital in Ethiopia, using validated tool TAI.
AB  - BACKGROUND: Asthma is a chronic inflammatory condition of the airways that
      affects roughly 358 million people globally. It is a serious global health
      problem with an increasing prevalence worldwide. Most people affected are in low-
      and middle-income countries including Ethiopia. The association between non 
      adherence and poor disease control is clearly stated in different literatures.
      The main objective of the present study was to assess self-reported non-
      adherence level and to identify the potential factors associated with non
      adherence. METHODS: An institution based cross-sectional study was conducted in
      university of Gondar teaching and referral hospital. The data was collected using
      a validated tool called Test of Adherence to Inhalers (TAI). RESULT: Among the
      total of study participants, higher proportions of patients were female (57.3%).
      Large number of the respondents (59.1%) were Unable to read and write. 18.3% of
      inhalational user asthmatic patients were not adherent to inhalational
      medications. According to this study only 49.4% of the respondents were adherent
      to inhalations and 32.3% of them were intermediate adherent to inhalational anti
      asthmatics medications. Lack of education about the Proper use of inhalational
      anti-asthmatics medications, poly pharmacy and co-morbidities were statistically
      significant factors associated with non-adherence. CONCLUSION: The rate of non
      adherence to inhalational anti asthmatics is high. Therefore, promoting optimal
      medication adherences through education, proper patient consultation is essential
      to optimize the benefits of treatment. Measurement of the degree of non-adherence
      to inhaled treatment in each individual patient is important in early
      interventional practice.

PMID- 29046816
TI  - Vitamin D binding protein is lower in infertile patients compared to fertile
      controls: a case control study.
AB  - BACKGROUND: The importance of vitamin D in general health as well as in human
      reproductive success has been an area of focus. A better understanding of vitamin
      D metabolism, particularly vitamin D binding protein, is important when
      elucidating this relationship. METHODS: This case control trial seeks to
      characterize vitamin D metabolism in infertile patients undergoing natural cycle
      IVF as compared to normally cycling premenopausal women with proven fertility
      matched for age and body mass index (BMI). A total of 68 subjects were examined;
      39 were infertile premenopausal women and 29 were regularly cycling fertile
      controls. Their 25-hydroxy vitamin D (25OHD), vitamin D binding protein (DBP),
      and albumin were measured and free and bioavailable 25OHD calculated. Between
      group comparisons were conducted with an unpaired t-test. A stepwise regression
      using age, BMI, 25OHD, estradiol & albumin in the model were used to determine
      predictors of DBP. RESULTS: Age, BMI, and total 25OHD did not differ between the
      two groups. However, vitamin D binding protein, free and bioavailable vitamin D
      were significantly different in the infertile patients as compared to the
      regularly cycling fertile controls (p < 0.01). Stepwise Regression using age,
      BMI, 25OHD, estradiol & albumin in the model showed that only albumin was a
      predictor of DBP (beta-coefficient - 0.310; p = 0.01). CONCLUSION: The
      implications of lower vitamin D binding protein associated with infertility is
      not clear from this pilot study, and requires further study.

PMID- 29046818
TI  - Fertility differential of women in Bangladesh demographic and health survey 2014.
AB  - BACKGROUND: The aim of this study was to examine the fertility differential of
      women age 15 to 49 using data from Bangladesh Demographic and Health Survey 2014-
      a survey of women who were born from 1963 to 1999. METHODS: The secondary data
      analysis was carried out using the BDHS 2014 in order to discuss differences in
      childbearing practices in Bangladesh. Descriptive statistics were used to analyze
      the data including education level, geographic location, and religion. A trend
      test used to assess the inferences. RESULTS: On average, women had 2.3 children
      in the BDHS 2014; more than 90% of them gave birth to at least one child by age
      49 and the average age of first birth was 18 years. Fertility of women strongly
      differed by education (p < 0.001). The percentage of women with secondary
      education who had no child was 50.3% and never attended school 8.4%;those with
      secondary education were six times as likely as those who never attended school
      to have no child and this pattern was stronger among urban compared with rural
      women. CONCLUSIONS: Fertility differential becomes robust as education increases.
      Women's fertility is also related to religion and residence, but these factors
      were not strongly related as those educational attainments.

PMID- 29046817
TI  - Fertility with early reduction of ovarian reserve: the last straw that breaks the
      Camel's back.
AB  - Diminished fertility and poor ovarian response pose a conundrum to the experts in
      the field of reproductive medicine. There is limited knowledge about the risk
      factors of diminished ovarian reserve other than the iatrogenic ones. One of the
      leading causes of infertility in women today is diminished ovarian reserve (DOR).
      DOR is characterized by a low number of eggs in a woman's ovaries and/or with
      poor quality of the remaining eggs, which boils down to impaired development of
      the existing eggs, even with assisted reproductive techniques. A good number of
      such women with low ovarian reserve may conceive with their own eggs, if they are
      given individualized treatment that is tailored for their profile. Such patients
      should be counseled appropriately for an aggressive approach towards achieving
      fertility. The sooner the treatment is started, the better the chances of
      pregnancy.

PMID- 29046819
TI  - Interpersonal art psychotherapy for the treatment of aggression in people with
      learning disabilities in secure care: a protocol for a randomised controlled
      feasibility study.
AB  - BACKGROUND: Art psychotherapy has greater potential for use with adults with mild
      to moderate learning disabilities as it places less of a burden on verbal
      interaction to achieve positive therapeutic, psychological, and behavioural
      goals. The feasibility study objectives include testing procedures, outcomes,
      validated tools, recruitment and attrition rates, acceptability, and treatment
      fidelity for manualised interpersonal art psychotherapy. METHODS: Adult males and
      females with mild to moderate learning disabilities will be recruited from four
      NHS secure hospitals. Twenty patients will be recruited and randomly assigned to
      one of two treatment groups: fifteen 1-h individual sessions of manualised
      interpersonal art psychotherapy, or a treatment as usual waiting list control
      group. The Modified Overt Aggression Scale will be administered to both treatment
      arms. Four patients will be recruited to a single-case design component of the
      study exploring the acceptability of an attentional condition. DISCUSSION: This
      multi-site study will assist in future trial planning and inform feasibility
      including, procedures, treatment acceptability, therapist adherence, and
      estimation of samples size for a definitive RCT.

PMID- 29046820
TI  - Bioimaging of botulinum toxin and hyaluronate hydrogels using zwitterionic near
      infrared fluorophores.
AB  - BACKGROUND: The injection of botulinum toxin (BTX) to reduce facial wrinkles is
      one of the most frequently performed plastic surgery procedures. The
      biocompatible hydrogels are injected with BTX for effective tissue augmentation.
      However, it is difficult to determine the interval of injection for effective
      tissue augmentation. METHOD: BTX and hyaluronate (HA) hydrogels were labeled with
      zwitterionic (ZW) near-infrared (NIR) fluorophores and visualized for 3 weeks
      after injection to BALB/c nude mice. RESULTS: BTX-ZW conjugates and diaminohexane
      (DAH)-HA-ZW hydrogels were successfully prepared by the conventional EDC/NHS
      chemistry. Using the NIR fluorescence imaging, we confirmed that approximately
      10% of BTX-ZW conjugates and 50% of DAH-HA-ZW hydrogels remained 3 weeks post
      injection. CONCLUSION: This bioimaging technique using invisible NIR fluorescence
      light can be exploited for various biomedical applications.

PMID- 29046821
TI  - Advances in medical adhesives inspired by aquatic organisms' adhesion.
AB  - In biomedicine, adhesives for hard and soft tissues are crucial for various
      clinical purposes. However, compared with that under dry conditions, adhesion
      performance in the presence of water or moisture is dramatically reduced. In this
      review, representative types of medical adhesives and the challenging aspects of
      wet adhesion are introduced. The adhesion mechanisms of marine mussels,
      sandcastle worms, and endoparasitic worms are described, and stemming from the
      insights gained, designs based on the chemistry of molecules like catechol and on
      coacervation and mechanical interlocking platforms are introduced in the
      viewpoint of translating these natural adhesion mechanisms into synthetic
      approaches.

PMID- 29046822
TI  - Polyion complex micelle formed from tetraphenylethene containing block copolymer.
AB  - BACKGROUND: Polymeric micelles attract great attention in drug delivery and
      therapeutics. Various types of block copolymers have been designed for the
      application in biomedical fields. If we can introduce additional functional
      groups to the block copolymers, we can achieve advanced applications. In this
      regards, we tried to introduce aggregation induced emission enhancement (AIE)
      unit in the block copolymer. METHODS: The formation of polyion complex micelle
      was confirmed by dynamic light scattering and transmission electron microscopy.
      HeLa cells were incubated with polyion complex micelle and broad-band visible
      light using a halogen lamp (150 W) was irradiated to evaluate photocytotoxicity
      of polyion complex (PIC) micelle. RESULTS: For the design of functional polymeric
      micelle, aggregation induced emission enhancement unit was introduced in the
      middle of block copolymer. We newly synthesized a new type block copolymer (PEG
      TPE-PEI) possessing tetraphenylethene (TPE) group, as an AIE unit, in the middle
      of polymeric segments of PEG and PEI, which successfully formed PIC micelle with
      DP. The formation of PIC micelle was confirmed by dynamic light scattering, zeta
      potential measurement and transmission electron microscopy. CONCLUSIONS: PEG-TPE
      PEI successfully formed PIC micelle by mixing with negatively charged dendrimer
      porphyrin. The PIC micelle exhibited photocytotoxicity upon illumination of
      broadband visible light.

PMID- 29046823
TI  - Functionalization of Ti-40Nb implant material with strontium by reactive
      sputtering.
AB  - BACKGROUND: Surface functionalization of orthopedic implants with
      pharmaceutically active agents is a modern approach to enhance osseointegration
      in systemically altered bone. A local release of strontium, a verified bone
      building therapeutic agent, at the fracture site would diminish side effects,
      which could occur otherwise by oral administration. Strontium surface
      functionalization of specially designed titanium-niobium (Ti-40Nb) implant alloy
      would provide an advanced implant system that is mechanically adapted to altered
      bone with the ability to stimulate bone formation. METHODS: Strontium-containing
      coatings were prepared by reactive sputtering of strontium chloride (SrCl2) in a
      self-constructed capacitively coupled radio frequency (RF) plasma reactor. Film
      morphology, structure and composition were investigated by scanning electron
      microscopy (SEM), time of flight secondary ion mass spectrometry (ToF-SIMS) and X
      ray photoelectron spectroscopy (XPS). High-resolution transmission electron
      microscopy (HR-TEM) was used for the investigation of thickness and growth
      direction of the product layer. TEM lamellae were prepared using the focused ion
      beam (FIB) technique. Bioactivity of the surface coatings was tested by
      cultivation of primary human osteoblasts and subsequent analysis of cell
      morphology, viability, proliferation and differentiation. The results are
      correlated with the amount of strontium that is released from the coating in
      biomedical buffer solution, quantified by inductively coupled plasma mass
      spectrometry (ICP-MS). RESULTS: Dense coatings, consisting of SrOxCly, of more
      than 100 nm thickness and columnar structure, were prepared. TEM images of cross
      sections clearly show an incoherent but well-structured interface between coating
      and substrate without any cracks. Sr2+ is released from the SrOxCly coating into
      physiological solution as proven by ICP-MS analysis. Cell culture studies showed
      excellent biocompatibility of the functionalized alloy. CONCLUSIONS: Ti-40Nb
      alloy, a potential orthopedic implant material for osteoporosis patients, could
      be successfully plasma coated with a dense SrOxCly film. The material performed
      well in in vitro tests. Nevertheless, the Sr2+ release must be optimized in
      future work to meet the requirements of an effective drug delivery system.

PMID- 29046824
TI  - Authentication of Algorithm to Detect Metastases in Men with Prostate Cancer
      Using ICD-9 Codes.
AB  - BACKGROUND: Metastasis is a crucial endpoint for patients with prostate cancer
      (PCa), but currently lacks a validated claims-based algorithm for detection.
      OBJECTIVE: To develop an algorithm using ICD-9 codes to facilitate accurate
      reporting of PCa metastases. METHODS: Medical records from 300 men hospitalized
      at Robert Wood Johnson University Hospital for PCa were reviewed. Using the
      presence of metastatic PCa on chart review as the gold standard, two algorithms
      to detect metastases were compared. Algorithm A used ICD-9 codes 198.5 (bone
      metastases), 197.0 (lung metastases), 197.7 (liver metastases), or 198.3 (brain
      and spinal cord metastases) to detect metastases, while algorithm B used only
      198.5. Sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) for the two algorithms were determined. Kappa statistics
      were used to measure agreement rates between claim data and chart review.
      RESULTS: Algorithm A demonstrated a sensitivity, specificity, PPV, and NPV of
      95%, 100%, 100%, and 98.7%, respectively. Corresponding numbers for algorithm B
      were 90%, 100%, 100%, and 97.5%, respectively. The agreement rate is 96.8% for
      algorithm A and 93.5% for algorithm B. CONCLUSIONS: Using ICD-9 codes 198.5,
      197.0, 197.7, or 198.3 in detecting the presence of PCa metastases offers a high
      sensitivity, specificity, PPV, and NPV value.

PMID- 29046825
TI  - Physicochemical and surface properties of acrylic intraocular lenses and their
      clinical significance.
AB  - To analyze and compare several commercially available acrylic intraocular lenses
      (IOLs) with particular regard to their clinical significance, we examined the
      physicochemical and surface properties of four currently available acrylic IOLs
      using static water contact angle, atomic force microscopy (AFM), Raman
      spectroscopy, and differential scanning calorimetry (DSC) measurements. The
      hydrophobic acrylic IOLs, ZA9003, and MA60BM, had contact angles ranging from
      77.9 degrees  +/- 0.65 degrees  to 84.4 degrees  +/- 0.09 degrees . The contact
      angles in the hydrophilic acrylic (970C) and heparin-surface-modified (HSM)
      hydrophilic acrylic IOLs (BioVue) were 61.8 degrees  +/- 0.45 degrees  and 69.7
      degrees  +/- 0.76 degrees , respectively. The roughness of the IOL optic surface
      differed depending on the type of IOL (p < 0.001). The surface roughness of
      BioVue had the lowest value: 5.87 +/- 1.26 nm. This suggests that the BioVue IOL
      may lead to reduced cellular adhesion compared to the unmodified IOLs. All IOLs
      including those composed of acrylic optic materials from different manufacturers
      showed distinct Raman spectra peaks. The glass transition temperatures (Tg) for
      the hydrophobic acrylic IOLs were between 12.5 and 13.8  degrees C. These results
      suggest that the intraoperative and postoperative behavior of an IOL can be
      predicted. This information is also expected to contribute greatly to the
      industrial production of reliable biocompatible IOLs.

PMID- 29046826
TI  - Incorporation of functional elements enhances the antitumor capacity of CAR T
      cells.
AB  - As chimeric antigen receptor (CAR) T cells have displayed an unprecedented
      efficacy in the treatment of CD19-positive malignances, it is believed that this
      cell therapy will be a milestone in the history of mankind's conquering of
      cancer. However, there are some issues that restrict CAR T cells from reaching
      their optimal anti-tumor capacity, especially in the treatment of solid tumors.
      Inhibitory cytokines, immune checkpoint molecules, hypoxia and other adverse
      factors have been reported to be involved in this process. To obtain better
      efficacy in the treatment of leukemia and solid tumors, we need to continuously
      upgrade CAR T cell technology by incorporating novel functional elements into CAR
      T cells to overcome these restrictions. In this review, we summarize recent
      advances regarding this topic.

PMID- 29046827
TI  - The Importance of Reviewers.

PMID- 29046828
TI  - Exploring Test-Retest Variability Using High-Resolution Perimetry.
AB  - PURPOSE: Test-retest variability (TRV) of visual field (VF) data seriously
      degrades our capacity to recognize true VF progression. We conducted repeated
      high-resolution perimetry with a test interval of 0.5 degrees  to investigate the
      sources of TRV. In particular, we examined whether the spatial variance of the
      observed sensitivity changes or if their absolute magnitude was of more
      importance. METHODS: Sixteen eyes of 16 glaucoma patients were each tested three
      times at 61 VF locations along the superior-temporal 45 degrees  meridian using a
      modified protocol of the Octopus 900 perimeter. TRV was quantified as the
      standard deviation of the repeats at each point (retest-SD). We also computed the
      mean sensitivity at each point (retest-MS) and the running spatial-SD along the
      tested meridian. Multiple regression models investigated whether any of those
      variables (and also age, sex, and VF eccentricity) were significant independent
      determinants of TRV. RESULTS: The main independent determinants of TRV were the
      retest-MS at -0.04 dB TRV/dB loss (P < 0.0001, t-statistic 5.05), and the retest
      SD at 0.47 dB spatial variance/dB loss (P < 0.0001, t-statistic 12.5).
      CONCLUSIONS: The larger effect for the spatial-SD suggested that it was perhaps a
      stronger determinant of TRV than scotoma depth per se. This might support the
      hypothesis that interactions between small perimetric stimuli, rapidly varying
      sensitivity across the field, and normal fixational jitter are strong
      determinants of TRV. TRANSLATIONAL RELEVANCE: Our study indicates that methods
      that might reduce the effects of jagged sensitivity changes, such as increasing
      stimulus size or better gaze tracking, could reduce TRV.

PMID- 29046830
TI  - Reviewers.

PMID- 29046829
TI  - Evaluation of a Sustained-Release Prednisolone Acetate Biodegradable
      Subconjunctival Implant in a Non-Human Primate Model.
AB  - PURPOSE: We evaluate the toxicity and plasma toxicokinetic (TK) profile of a
      biodegradable subconjunctival microrod for sustained prednisolone acetate (PA)
      release over 12 weeks in a non-human primate model. METHODS: The biodegradable
      copolymer poly(l-lactide-co-epsilon-caprolactone) (PLC) and 40-wt% PA microrods
      were used and fashioned into 8 and 16 mm lengths. Twelve monkeys were divided
      into two treatment groups of PA-loaded and blank microrods, with six monkeys each
      receiving either 8- or 16-mm microrods subconjunctively implanted into both eyes.
      TK and hematology parameters were analyzed. Ophthalmic clinical evaluation,
      including slit-lamp and ophthalmoscopy examinations, was performed. RESULTS: Over
      the study period of 12 weeks, the mean area under the plasma concentration-time
      curve was 45.7% higher, and the maximum plasma concentration was 17.2% lower for
      the animals treated with 40-wt% PA 16-mm microrods compared to 8-mm microrods
      (251.44 versus 172.54 hours * nanograms per milliliter and 8.53 versus 10.30
      ng/mL, respectively). The PA release was significantly below the levels of
      assumed toxicity. There was no significant difference in the time to reach
      maximum concentration between the 8- and 16-mm microrod groups (7.33 and 8 hours;
      P = 0.421). Findings from clinical evaluation, hematology, and histopathology
      showed no ocular side effects and no significant adverse systemic effects.
      CONCLUSION: The PA biodegradable microrods demonstrated safe toxicokinetics even
      with the larger size implant containing a higher amount of drug. The PA implant
      may be considered as a safe alternative to the application of topical PA
      eyedrops. TRANSLATIONAL RELEVANCE: The results provide the evidence of the safety
      of implanting a steroid delivery system subconjunctively, offering an alternative
      to topical PA eyedrops.

PMID- 29046831
TI  - Self-assembly of chiral fluorescent nanoparticles based on water-soluble L
      tryptophan derivatives of p-tert-butylthiacalix[4]arene.
AB  - New water-soluble tetra-substituted derivatives of p-tert-butylthiacalix[4]arene
      containing fragments of L-tryptophan in cone and 1,3-alternate conformations were
      obtained. It was shown that the resulting compounds form stable, positively
      charged aggregates of 86-134 nm in diameter in water at a concentration of 1 * 10
      4 M as confirmed by dynamic light scattering, scanning electron microscopy and
      transmission electron microscopy. It was established that these aggregates are
      fluorescently active and chiral. A distinctive feature of the compounds is the
      pronounced dependence of their spectral (emission and chiroptical) properties on
      the polarity of the solvent and the length of the linker between the macrocyclic
      and fluorophore parts of the molecule.

PMID- 29046832
TI  - Structural model of silicene-like nanoribbons on a Pb-reconstructed Si(111)
      surface.
AB  - A structural model of the recently observed silicene-like nanoribbons on a Pb
      induced ?3 * ?3 reconstructed Si(111) surface is proposed. The model, which is
      based on first principles density functional theory calculations, features a
      deformed honeycomb structure directly bonded to the Si(111) surface underneath.
      Pb atoms stabilize the nanoribbons, as they passivate the uncovered substrate,
      thus lower the surface energy, and suppress the nanoribbon-substrate interaction.
      The proposed structural model reproduces well all the experimental findings.

PMID- 29046834
TI  - Application of visible-light photosensitization to form alkyl-radical-derived
      thin films on gold.
AB  - Visible-light irradiation of phthalimide esters in the presence of the
      photosensitizer [Ru(bpy)3]2+ and the stoichiometric reducing agent benzyl
      nicotinamide results in the formation of alkyl radicals under mild conditions.
      This approach to radical generation has proven useful for the synthesis of small
      organic molecules. Herein, we demonstrate for the first time the visible-light
      photosensitized deposition of robust alkyl thin films on Au surfaces using
      phthalimide esters as the alkyl radical precursors. In particular, we combine
      visible-light photosensitization with particle lithography to produce
      nanostructured thin films, the thickness of which can be measured easily using
      AFM cursor profiles. Analysis with AFM demonstrated that the films are robust and
      resistant to mechanical force while contact angle goniometry suggests a
      multilayered and disordered film structure. Analysis with IRRAS, XPS, and TOF
      SIMS provides further insights.

PMID- 29046833
TI  - Optical techniques for cervical neoplasia detection.
AB  - This paper provides an overview of the current research in the field of optical
      techniques for cervical neoplasia detection and covers a wide range of the
      existing and emerging technologies. Using colposcopy, a visual inspection of the
      uterine cervix with a colposcope (a binocular microscope with 3- to 15-fold
      magnification), has proven to be an efficient approach for the detection of
      invasive cancer. Nevertheless, the development of a reliable and cost-effective
      technique for the identification of precancerous lesions, confined to the
      epithelium (cervical intraepithelial neoplasia) still remains a challenging
      problem. It is known that even at early stages the neoplastic transformations of
      cervical tissue induce complex changes and modify both structural and biochemical
      properties of tissues. The different methods, including spectroscopic (diffuse
      reflectance spectroscopy, induced fluorescence and autofluorescence spectroscopy,
      Raman spectroscopy) and imaging techniques (confocal microscopy, optical
      coherence tomography, Mueller matrix imaging polarimetry, photoacoustic imaging),
      probe different tissue properties that may serve as optical biomarkers for
      diagnosis. Both the advantages and drawbacks of these techniques for the
      diagnosis of cervical precancerous lesions are discussed and compared.

PMID- 29046835
TI  - Carbon nano-onions as fluorescent on/off modulated nanoprobes for diagnostics.
AB  - Multishell fullerenes, known as carbon nano-onions (CNOs), have emerged as a
      platform for bioimaging because of their cell-penetration properties and minimal
      systemic toxicity. Here, we describe the covalent functionalization of CNOs with
      a pi-extended distyryl-substituted boron dipyrromethene (BODIPY) dye with on/off
      modulated fluorescence emission activated by an acidic environment. The switching
      properties are linked to the photoinduced electron transfer (PET) characteristics
      of the dimethylamino functionalities attached to the BODIPY core. The on/off
      emission of the fluorescent CNOs is fast and reversible both in solution and in
      vitro, making this nanomaterial suitable as pH-dependent probes for diagnostic
      applications.

PMID- 29046836
TI  - Stick-slip boundary friction mode as a second-order phase transition with an
      inhomogeneous distribution of elastic stress in the contact area.
AB  - This article presents an investigation of the dynamical contact between two
      atomically flat surfaces separated by an ultrathin lubricant film. Using a
      thermodynamic approach we describe the second-order phase transition between two
      structural states of the lubricant which leads to the stick-slip mode of boundary
      friction. An analytical description and numerical simulation with radial
      distributions of the order parameter, stress and strain were performed to
      investigate the spatial inhomogeneity. It is shown that in the case when the
      driving device is connected to the upper part of the friction block through an
      elastic spring, the frequency of the melting/solidification phase transitions
      increases with time.

PMID- 29046837
TI  - Fabrication of carbon nanospheres by the pyrolysis of polyacrylonitrile
      poly(methyl methacrylate) core-shell composite nanoparticles.
AB  - Carbon nanospheres with a high Brunauer-Emmett-Teller (BET) specific surface area
      were fabricated via the pyrolysis of polyacrylonitrile-poly(methyl methacrylate)
      (PAN-PMMA) core-shell nanoparticles. Firstly, PAN-PMMA nanoparticles at high
      concentration and low surfactant content were controllably synthesized by a two
      stage azobisisobutyronitrile (AIBN)-initiated semicontinuous emulsion
      polymerization. The carbon nanospheres were obtained after the PAN core domain
      was converted into carbon and the PMMA shell was sacrificed via the subsequent
      heat treatment steps. The thickness of the PMMA shell can be easily adjusted by
      changing the feeding volume ratio (FVR) of methyl methacrylate (MMA) to
      acrylonitrile (AN). At an FVR of 1.6, the coarse PAN cores were completely buried
      in the PMMA shells, and the surface of the obtained PAN-PMMA nanoparticles became
      smooth. The thick PMMA shell can inhibit the adhesion between carbon nanospheres
      caused by cyclization reactions during heat treatment. The carbon nanospheres
      with a diameter of 35-65 nm and a high BET specific surface area of 612.8 m2/g
      were obtained from the PAN-PMMA nanoparticles synthesized at an FVR of 1.6. The
      carbon nanospheres exhibited a large adsorption capacity of 190.0 mg/g for
      methylene blue, thus making them excellent adsorbents for the removal of organic
      pollutants from water.

PMID- 29046838
TI  - Enhancement of mechanical and electrical properties of continuous-fiber
      reinforced epoxy composites with stacked graphene.
AB  - Impregnation of expandable graphite (EG) after thermal treatment with an epoxy
      resin containing surface-active agents (SAAs) enhanced the intercalation of epoxy
      monomer between EG layers and led to further exfoliation of the graphite,
      resulting in stacks of few graphene layers, so-called "stacked" graphene (SG).
      This process enabled electrical conductivity of cured epoxy/SG composites at
      lower percolation thresholds, and improved thermo-mechanical properties were
      measured with either Kevlar, carbon or glass-fiber-reinforced composites. Several
      compositions with SAA-modified SG led to higher dynamic moduli especially at high
      temperatures, reflecting the better wetting ability of the modified
      nanoparticles. The hydrophilic/hydrophobic nature of the SAA dictates the surface
      energy balance. More hydrophilic SAAs promoted localization of the SG at the
      Kevlar/epoxy interface, and morphology seems to be driven by thermodynamics,
      rather than the kinetic effect of viscosity. This effect was less obvious with
      carbon or glass fibers, due to the lower surface energy of the carbon fibers or
      some incompatibility with the glass-fiber sizing. Proper choice of the surfactant
      and fine-tuning of the crosslink density at the interphase may provide further
      enhancements in thermo-mechanical behavior.

PMID- 29046839
TI  - Spin-dependent transport and functional design in organic ferromagnetic devices.
AB  - Organic ferromagnets are intriguing materials in that they combine ferromagnetic
      and organic properties. Although challenges in their synthesis still remain, the
      development of organic spintronics has triggered strong interest in high
      performance organic ferromagnetic devices. This review first introduces our
      theory for spin-dependent electron transport through organic ferromagnetic
      devices, which combines an extended Su-Schrieffer-Heeger model with the Green's
      function method. The effects of the intrinsic interactions in the organic
      ferromagnets, including strong electron-lattice interaction and spin-spin
      correlation between pi-electrons and radicals, are highlighted. Several
      interesting functional designs of organic ferromagnetic devices are discussed,
      specifically the concepts of a spin filter, multi-state magnetoresistance, and
      spin-current rectification. The mechanism of each phenomenon is explained by
      transmission and orbital analysis. These works show that organic ferromagnets are
      promising components for spintronic devices that deserve to be designed and
      examined in future experiments.

PMID- 29046840
TI  - Freestanding graphene/MnO2 cathodes for Li-ion batteries.
AB  - Different polymorphs of MnO2 (alpha-, beta-, and gamma-) were produced by
      microwave hydrothermal synthesis, and graphene oxide (GO) nanosheets were
      prepared by oxidation of graphite using a modified Hummers' method. Freestanding
      graphene/MnO2 cathodes were manufactured through a vacuum filtration process. The
      structure of the graphene/MnO2 nanocomposites was characterized using X-ray
      diffraction (XRD) and Raman spectroscopy. The surface and cross-sectional
      morphologies of freestanding cathodes were investigated by scanning electron
      microcopy (SEM). The charge-discharge profile of the cathodes was tested between
      1.5 V and 4.5 V at a constant current of 0.1 mA cm-2 using CR2016 coin cells. The
      initial specific capacity of graphene/alpha-, beta-, and gamma-MnO2 freestanding
      cathodes was found to be 321 mAhg-1, 198 mAhg-1, and 251 mAhg-1, respectively.
      Finally, the graphene/alpha-MnO2 cathode displayed the best cycling performance
      due to the low charge transfer resistance and higher electrochemical reaction
      behavior. Graphene/alpha-MnO2 freestanding cathodes exhibited a specific capacity
      of 229 mAhg-1 after 200 cycles with 72% capacity retention.

PMID- 29046841
TI  - Growth and characterization of textured well-faceted ZnO on planar Si(100),
      planar Si(111), and textured Si(100) substrates for solar cell applications.
AB  - In this work, textured, well-faceted ZnO materials grown on planar Si(100),
      planar Si(111), and textured Si(100) substrates by low-pressure chemical vapor
      deposition (LPCVD) were analyzed by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), atomic force microscopy (AFM), and cathode luminescence (CL)
      measurements. The results show that ZnO grown on planar Si(100), planar Si(111),
      and textured Si(100) substrates favor the growth of ZnO(110) ridge-like, ZnO(002)
      pyramid-like, and ZnO(101) pyramidal-tip structures, respectively. This could be
      attributed to the constraints of the lattice mismatch between the ZnO and Si unit
      cells. The average grain size of ZnO on the planar Si(100) substrate is slightly
      larger than that on the planar Si(111) substrate, while both of them are much
      larger than that on the textured Si(100) substrate. The average grain sizes
      (about 10-50 nm) of the ZnO grown on the different silicon substrates decreases
      with the increase of their strains. These results are shown to strongly correlate
      with the results from the SEM, AFM, and CL as well. The reflectance spectra of
      these three samples show that the antireflection function provided by theses
      samples mostly results from the nanometer-scaled texture of the ZnO films, while
      the micrometer-scaled texture of the Si substrate has a limited contribution. The
      results of this work provide important information for optimized growth of
      textured and well-faceted ZnO grown on wafer-based silicon solar cells and can be
      utilized for efficiency enhancement and optimization of device materials and
      structures, such as heterojunction with intrinsic thin layer (HIT) solar cells.

PMID- 29046842
TI  - Coexistence of strongly buckled germanene phases on Al(111).
AB  - We report a study of structural and electronic properties of a germanium layer on
      Al(111) using scanning tunneling microscopy (STM), low energy electron
      diffraction and core-level photoelectron spectroscopy. Experimental results show
      that a germanium layer can be formed at a relatively high substrate temperature
      showing either (3*3) or (?7*?7)R+/-19.1 degrees  reconstructions. First
      principles calculations based on density functional theory suggest an atomic
      model consisting of a strongly buckled (2*2) germanene layer, which is stable in
      two different orientations on Al(111). Simulated STM of both orientations fit
      nicely with experimental STM images and the Ge 3d core-level data decomposed into
      four components is consistent with the suggested model.

PMID- 29046843
TI  - Intercalation of Si between MoS2 layers.
AB  - We report a combined experimental and theoretical study of the growth of sub
      monolayer amounts of silicon (Si) on molybdenum disulfide (MoS2). At room
      temperature and low deposition rates we have found compelling evidence that the
      deposited Si atoms intercalate between the MoS2 layers. Our evidence relies on
      several experimental observations: (1) Upon the deposition of Si on pristine MoS2
      the morphology of the surface transforms from a smooth surface to a hill-and
      valley surface. The lattice constant of the hill-and-valley structure amounts to
      3.16 A, which is exactly the lattice constant of pristine MoS2. (2) The
      transitions from hills to valleys are not abrupt, as one would expect for
      epitaxial islands growing on-top of a substrate, but very gradual. (3) I(V)
      scanning tunneling spectroscopy spectra recorded at the hills and valleys reveal
      no noteworthy differences. (4) Spatial maps of dI/dz reveal that the surface
      exhibits a uniform work function and a lattice constant of 3.16 A. (5) X-ray
      photo-electron spectroscopy measurements reveal that sputtering of the MoS2/Si
      substrate does not lead to a decrease, but an increase of the relative Si signal.
      Based on these experimental observations we have to conclude that deposited Si
      atoms do not reside on the MoS2 surface, but rather intercalate between the MoS2
      layers. Our conclusion that Si intercalates upon the deposition on MoS2 is at
      variance with the interpretation by Chiappe et al. (Adv. Mater.2014, 26, 2096
      2101) that silicon forms a highly strained epitaxial layer on MoS2. Finally,
      density functional theory calculations indicate that silicene clusters
      encapsulated by MoS2 are stable.

PMID- 29046844
TI  - Imidazolium-based ionic liquids used as additives in the nanolubrication of
      silicon surfaces.
AB  - In recent years, with the development of micro/nanoelectromechanical systems
      (MEMS/NEMS), the demand for efficient lubricants of silicon surfaces intensified.
      Although the use of ionic liquids (ILs) as additives to base oils in the
      lubrication of steel/steel or other types of metal/ metal tribological pairs has
      been investigated, the number of studies involving Si is very low. In this work,
      we tested imidazolium-based ILs as additives to the base oil polyethylene glycol
      (PEG) to lubricate Si surfaces. The friction coefficients were measured in a
      nanotribometer. The viscosity of the PEG + IL mixtures as well as their contact
      angles on the Si surface were measured. The topography and chemical composition
      of the substrates surfaces were determined with atomic force microscopy (AFM) and
      X-ray photoelectron spectroscopy (XPS), respectively. Due to the hygroscopic
      properties of PEG, the first step was to assess the effect of the presence of
      water. Then, a series of ILs based on the cations 1-ethyl-3-methylimidazolium
      [EMIM], 1-butyl-3-methylimidazolium [BMIM], 1-ethyl-3-vinylimidazolium [EVIM], 1
      (2-hydroxyethyl)-3-methylimidazolium [C2OHMIM] and 1-allyl-3-methylimidazolium
      [AMIM] combined with the anions dicyanamide [DCA], trifluoromethanesulfonate
      [TfO], and ethylsulfate [EtSO4] were added to dry PEG. All additives (2 wt %) led
      to a decrease in friction coefficient as well as an increase in viscosity (with
      the exception of [AMIM][TfO]) and improved the Si wettability. The additives
      based on the anion [EtSO4] exhibited the most promising tribological behavior,
      which was attributed to the strong interaction with the Si surface ensuring the
      formation of a stable surface layer, which hinders the contact between the
      sliding surfaces.

PMID- 29046845
TI  - Identifying the nature of surface chemical modification for directed self
      assembly of block copolymers.
AB  - In recent years, block copolymer lithography has emerged as a viable alternative
      technology for advanced lithography. In chemical-epitaxy-directed self-assembly,
      the interfacial energy between the substrate and each block copolymer domain
      plays a key role on the final ordering. Here, we focus on the experimental
      characterization of the chemical interactions that occur at the interface built
      between different chemical guiding patterns and the domains of the block
      copolymers. We have chosen hard X-ray high kinetic energy photoelectron
      spectroscopy as an exploration technique because it provides information on the
      electronic structure of buried interfaces. The outcome of the characterization
      sheds light onto key aspects of directed self-assembly: grafted brush layer,
      chemical pattern creation and brush/block co-polymer interface.

PMID- 29046846
TI  - Bi-layer sandwich film for antibacterial catheters.
AB  - Background: Approximately one quarter of all nosocomial infections can be
      attributed to the urinary tract. The infections are supposed to be mainly caused
      by implantations of urethral catheters and stents. A new catheter design is
      introduced with the aim to lower the high number of nosocomial urethral
      infections. In order to avoid limitations to use, the design is first applied to
      conventional commercially available balloon catheters. Results: The main feature
      of the design is a sandwich layer on both sides of the catheter wall, which is
      composed of a fragmented base layer of silver capped by a thin film of poly(p
      xylylene). This top layer is mainly designed to release a controlled amount of
      Ag+ ions, which is bactericidal, but not toxic to humans. Simultaneously, the
      lifetime is prolonged to at least one year. The base layer is electrolessly
      deposited applying Tollens' reagens, the cap layer is deposited by using chemical
      vapor deposition. Conclusion: The three main problems of this process,
      electroless deposition of a fragmented silver film on the surface of an
      electrically insulating organic polymer, irreproducible evaporation during
      heating of the precursor, and exponential decrease of the layer thickness along
      the capillary, have been solved trough the application of a simple
      electrochemical reaction and two standard principles of physics: Papin's pot and
      the principle of Le Chatelier.

PMID- 29046847
TI  - Advances and challenges in the field of plasma polymer nanoparticles.
AB  - This contribution reviews plasma polymer nanoparticles produced by gas
      aggregation cluster sources either via plasma polymerization of volatile monomers
      or via radio frequency (RF) magnetron sputtering of conventional polymers. The
      formation of hydrocarbon, fluorocarbon, silicon- and nitrogen-containing plasma
      polymer nanoparticles as well as core@shell nanoparticles based on plasma
      polymers is discussed with a focus on the development of novel nanostructured
      surfaces.

PMID- 29046848
TI  - Functional materials for environmental sensors and energy systems.

PMID- 29046849
TI  - A systematic study of the controlled generation of crystalline iron oxide
      nanoparticles on graphene using a chemical etching process.
AB  - Chemical vapor deposition (CVD) of carbon precursors employing a metal catalyst
      is a well-established method for synthesizing high-quality single-layer graphene.
      Yet the main challenge of the CVD process is the required transfer of a graphene
      layer from the substrate surface onto a chosen target substrate. This process is
      delicate and can severely degrade the quality of the transferred graphene. The
      protective polymer coatings typically used generate residues and contamination on
      the ultrathin graphene layer. In this work, we have developed a graphene transfer
      process which works without a coating and allows the transfer of graphene onto
      arbitrary substrates without the need for any additional post-processing. During
      the course of our transfer studies, we found that the etching process that is
      usually employed can lead to contamination of the graphene layer with the
      Faradaic etchant component FeCl3, resulting in the deposition of iron oxide Fe x
      O y nanoparticles on the graphene surface. We systematically analyzed the removal
      of the copper substrate layer and verified that crystalline iron oxide
      nanoparticles could be generated in controllable density on the graphene surface
      when this process is optimized. It was further confirmed that the Fe x O y
      particles on graphene are active in the catalytic growth of carbon nanotubes when
      employing a water-assisted CVD process.

PMID- 29046850
TI  - Preparation and characterization of polycarbonate/multiwalled carbon nanotube
      nanocomposites.
AB  - A polymer nanocomposite was produced by ultrasonic-assisted dispersion of
      multiwalled carbon nanotubes (MWCNTs) in a polycarbonate matrix using p-xylene
      and dichloromethane as the solvents. The filler loading was varied from 1 to 3 wt
      % in order to examine the effect of MWCNTs on the structure and properties of the
      composites. The nanocomposites were characterized by DSC, DTA, TGA, UV-vis, FTIR
      and Raman spectroscopy to evaluate the changes induced by the filler in the
      polymer matrix. UV-vis, FTIR and Raman spectroscopy measurements confirmed the
      presence of the dispersed phase in the composite films, while TGA and DSC
      analysis of the nanocomposites revealed enhanced thermal stability and decreased
      crystallinity, respectively, as compared to the neat polymer. The proposed
      composites can find application in a number of everyday products where
      polycarbonate is the base polymer.

PMID- 29046851
TI  - Systematic control of alpha-Fe2O3 crystal growth direction for improved
      electrochemical performance of lithium-ion battery anodes.
AB  - alpha-Fe2O3 nanomaterials with an elongated nanorod morphology exhibiting
      superior electrochemical performance were obtained through hydrothermal synthesis
      assisted by diamine derivatives as shape-controlling agents (SCAs) for
      application as anodes in lithium-ion batteries (LIBs). The physicochemical
      characteristics were investigated via XRD and FESEM, revealing well-crystallized
      alpha-Fe2O3 with adjustable nanorod lengths between 240 and 400 nm and aspect
      ratios in the range from 2.6 to 5.7. The electrochemical performance was
      evaluated by cyclic voltammetry and charge-discharge measurements. A SCA test
      series, including ethylenediamine, 1,2-diaminopropane, 2,3-diaminobutane, and N
      methylethylenediamine, was implemented in terms of the impact on the nanorod
      aspect ratio. Varied substituents on the vicinal diamine structure were examined
      towards an optimized reaction center in terms of electron density and steric
      hindrance. Possible interaction mechanisms of the diamine derivatives with ferric
      species and the correlation between the aspect ratio and electrochemical
      performance are discussed. Intermediate-sized alpha-Fe2O3 nanorods with
      length/aspect ratios of ~240 nm/~2.6 and ~280 nm/~3.0 were found to have
      excellent electrochemical characteristics with reversible discharge capacities of
      1086 and 1072 mAh g-1 at 0.1 C after 50 cycles.

PMID- 29046852
TI  - A comparative study of the nanoscale and macroscale tribological attributes of
      alumina and stainless steel surfaces immersed in aqueous suspensions of
      positively or negatively charged nanodiamonds.
AB  - This article reports a comparative study of the nanoscale and macroscale
      tribological attributes of alumina and stainless steel surfaces immersed in
      aqueous suspensions of positively (hydroxylated) or negatively (carboxylated)
      charged nanodiamonds (ND). Immersion in -ND suspensions resulted in a decrease in
      the macroscopic friction coefficients to values in the range 0.05-0.1 for both
      stainless steel and alumina, while +ND suspensions yielded an increase in
      friction for stainless steel contacts but little to no increase for alumina
      contacts. Quartz crystal microbalance (QCM), atomic force microscopy (AFM) and
      scanning electron microscopy (SEM) measurements were employed to assess
      nanoparticle uptake, surface polishing, and resistance to solid-liquid
      interfacial shear motion. The QCM studies revealed abrupt changes to the surfaces
      of both alumina and stainless steel upon injection of -ND into the surrounding
      water environment that are consistent with strong attachment of NDs and/or
      chemical changes to the surfaces. AFM images of the surfaces indicated slight
      increases in the surface roughness upon an exposure to both +ND and -ND
      suspensions. A suggested mechanism for these observations is that carboxylated 
      NDs from aqueous suspensions are forming robust lubricious deposits on stainless
      and alumina surfaces that enable gliding of the surfaces through the -ND
      suspensions with relatively low resistance to shear. In contrast, +ND suspensions
      are failing to improve tribological performance for either of the surfaces and
      may have abraded existing protective boundary layers in the case of stainless
      steel contacts. This study therefore reveals atomic scale details associated with
      systems that exhibit starkly different macroscale tribological properties,
      enabling future efforts to predict and design complex lubricant interfaces.

PMID- 29046853
TI  - Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by a Carbonylation-Cyclization Domino
      Reaction of ortho-Halophenols and Cyanamide.
AB  - Invited for this month's cover are researchers from the Division of Organic
      Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University
      (Sweden). The research interests in the group span areas such as enzyme
      inhibitors, new antibiotics, angiotensin II AT2R ligands, PET tracers, palladium
      catalysis, heterocycle synthesis, and the development of novel multicomponent
      reactions. In particular, sequential carbonylation and cyclization appeal to us
      as a convenient and straightforward synthetic route for the synthesis of
      heterocycles. The cover picture shows how carbon monoxide gas is diffused over a
      bridge, in the two-chamber system set-up used in this work, to take part in the
      catalytic cycle, and be incorporated into the heterocyclic core by a
      carbonylation/cyclization domino reaction to yield4H -benzo[e][1,3]oxazin-4-ones.
      For more details, see the full text of the Full Paper at 10.1002/open.201700130.

PMID- 29046854
TI  - Tannins and Their Complex Interaction with Different Organic Nitrogen Compounds
      and Enzymes: Old Paradigms versus Recent Advances.
AB  - Tannins, an abundant group of plant secondary compounds, raise interest in
      different fields of science, owing to their unique chemical characteristics. In
      chemical ecology, tannins play a crucial role in plant defense against pathogens,
      herbivores, and changing environmental conditions. In the food industry and in
      medicine, tannins are important because of their proven positive effect on human
      health and disease treatment. Such wide interests fueled studies on tannin
      chemistry, especially on their flagship ability to precipitate proteins. In this
      Review, we expand the basic knowledge on tannin chemistry to the newest insights
      from the field. We focus especially on tannin reactions with different non
      protein organic N compounds, as well as the complex interactions of tannins with
      enzymes, resulting in either an increase or decrease in enzyme activity.

PMID- 29046855
TI  - Specific Binding of Liposomal Nanoparticles through Inverse Electron-Demand Diels
      Alder Click Chemistry.
AB  - Here, we report a method to specifically bind liposomal radiopharmaceuticals to a
      CoCrMo alloy, which can be used in arterial stents, via an irreversible inverse
      electron-demand Diels-Alder reaction. Inspired by recent accomplishments in pre
      targeted imaging using tetrazine-trans-cyclooctene click chemistry, we
      synthesized 89Zr-labeled trans-cyclooctene-functionalized liposomal
      nanoparticles, which were validated on a tetrazine-appended polydopamine-coated
      CoCrMo surface. In efforts to ultimately translate this new material to
      biomedical applications, we compared the ability of 89Zr-TCO-liposomal
      nanoparticles (89Zr-TCO-LNP) to be immobilized on the tetrazine surface to the
      control suspensions of non-TCO functionalized 89Zr-liposomal nanoparticles.
      Ultimately, this platform technology could result in a systemic decrease of the
      radiotherapeutic dose deposited in non-targeted tissues by specific removal of
      long-circulating liposomal radiopharmaceuticals from the blood pool.

PMID- 29046856
TI  - Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by a Carbonylation-Cyclization Domino
      Reaction of ortho-Halophenols and Cyanamide.
AB  - A mild and convenient one-step preparation of 4H-1,3-benzoxazin-4-ones by a
      domino carbonylation-cyclization process is developed. Readily available ortho
      iodophenols are subjected to palladium-catalyzed carbonylative coupling with
      Mo(CO)6 and cyanamide, followed by a spontaneous, intramolecular cyclization to
      afford 4H-1,3-benzoxazin-4-ones in moderate to excellent yields. Furthermore, the
      scope of the reaction is extended to include challenging ortho-bromophenols.
      Finally, to highlight the versatility of the developed method, Mo(CO)6 is
      successfully replaced with a wide array of CO-releasing reagents, such as oxalyl
      chloride, phenyl formate, 9-methylfluorene-9-carbonyl chloride, and formic acid,
      making this an appealing strategy for the synthesis of 4H-benzo[e][1,3]oxazin-4
      ones.

PMID- 29046857
TI  - Voltage Oscillations in a Polymer Electrolyte Membrane Fuel Cell with Pd-Pt/C and
      Pd/C Anodes.
AB  - Polymer electrolyte membrane fuel cells (PEMFC) fed with H2 contaminated with CO
      may exhibit oscillatory behavior when operated galvanostatically. The self
      organization of the anodic overpotential is interesting because it can be
      accompanied by an increase in the average performance. Herein we report
      experimental studies of voltage oscillations that emerge in a PEMFC equipped with
      a Pd/C or PdPt/C anode and fed with H2 contaminated with CO (100 ppm). We used on
      line mass spectrometry to investigate how the mass fragments associated with CO2
      and CO (m/z 44 and 28, respectively) varied with the voltage oscillations.
      Overall, we observed that oscillations in the anodic overpotential are in phase
      with that of the CO and CO2 signals. This fact is consistent with an autonomous
      adsorption-oxidation cyclic process. For both anodes, it has been observed that,
      in general, an increase in current density implies an increase in oscillatory
      frequency. By using CO stripping, we also discuss how the onset of CO oxidation
      is related to the maximum overpotential reached during a cycle, whereas the
      minimum overpotential can be associated with the catalytic activity of the
      electrode for H2 oxidation.

PMID- 29046858
TI  - Fabrication of Poly(styrene-co-maleic anhydride)@Ag Spheres with High Surface
      Charge Intensity and their Self-Assembly into Photonic Crystal Films.
AB  - Herein, we developed a method to prepare monodisperse poly(styrene-co-maleic
      anhydride)@Ag (PSMA@Ag) core-shell microspheres with high surface charge
      intensity by using an in situ reduction method. In this method, ethylenediamine
      tetraacetic acid tetrasodium salt (Na4EDTA) was used as a reducing agent to
      promote the growth of Ag, and at the same time endowed the PSMA@Ag spheres with a
      surface charge. The monodispersity of PSMA and PSMA@Ag and the ordered array of
      the photonic crystal films were characterized by using SEM. The formation of Ag
      nanoparticles was confirmed by using TEM, HR-TEM, and XRD characterizations. Due
      to the existence of surface charges, the obtained PSMA@Ag microspheres easily
      self-assembled to form photonic crystal structures. In addition, the surface
      enhanced Raman scattering (SERS) activity of the PSMA@Ag photonic crystal films
      was evaluated by detecting the signal from Raman probe molecules, 4
      aminothiophenol (4-ATP). The PSMA@Ag photonic crystal films exhibited a high SERS
      effect, a low detection limit of up to 10-8 for 4-ATP, good uniformity, and
      reproducibility.

PMID- 29046859
TI  - The Design of Radical Stacks: Nitronyl-Nitroxide-Substituted Heteropentacenes.
AB  - The first alkyl chain-anchored heteropentacene, dithieno[2,3-d;2',3'-d']benzo
      [1,2-b;3,4-b']dithiophene (DTmBDT), mono- or disubstituted with a nitronyl
      nitroxide group has been prepared through a cross-coupling synthetic procedure of
      the corresponding dibromo-derivative (Br2-DTmBDT) with a nitronyl nitroxide-2-ide
      gold(I) complex. The synthesized nitroxides possess high kinetic stability, which
      allowed us to investigate their structure and thermal, optical, electrochemical,
      and magnetic properties. Single-crystal X-ray diffraction of both mono- and
      diradicals revealed that the nitronyl nitroxide group lies almost in the same
      plane as the nearest side thiophene ring. Such arrangement favors formation of
      edge-to-edge dimers, which then form close pi-stacks surrounded by
      interdigitating alkyl chains. Before melting, these nitronyl nitroxide radical
      substituted molecules undergo at least two different phase transitions (PTs): for
      the monoradical, PTs are reversible, accompanied by hysteresis, and occur near 13
      and 83  degrees C; the diradical upon heating shows a reversible PT with
      hysteresis in the temperature range 2-11  degrees C and an irreversible PT near
      135  degrees C. PTs of this type are absent in Br2-DTmBDT. Therefore, the step-by
      step substitution of bromine atoms by nitronyl nitroxide groups changes the
      structural organization of DTmBDT and induces the emergence of PTs. This
      knowledge may facilitate crystal engineering of pi-stacked paramagnets and
      related molecular spin devices.

PMID- 29046860
TI  - Two New Fluorogenic Aptasensors Based on Capped Mesoporous Silica Nanoparticles
      to Detect Ochratoxin A.
AB  - Aptamers have been used as recognition elements for several molecules due to
      their great affinity and selectivity. Additionally, mesoporous nanomaterials have
      demonstrated great potential in sensing applications. Based on these concepts, we
      report herein the use of two aptamer-capped mesoporous silica materials for the
      selective detection of ochratoxin A (OTA). A specific aptamer for OTA was used to
      block the pores of rhodamine B-loaded mesoporous silica nanoparticles. Two solids
      were prepared in which the aptamer capped the porous scaffolds by using a
      covalent or electrostatic approach. Whereas the prepared materials remained
      capped in water, dye delivery was selectively observed in the presence of OTA.
      The protocol showed excellent analytical performance in terms of sensitivity
      (limit of detection: 0.5-0.05 nm), reproducibility, and selectivity. Moreover,
      the aptasensors were tested for OTA detection in commercial foodstuff matrices,
      which demonstrated their potential applicability in real samples.

PMID- 29046861
TI  - Quinoline-Derived Two-Photon-Sensitive Octupolar Probes.
AB  - A systematic study on quinoline-derived light sensitive probes, having third
      order rotational symmetry is presented. The electronically linked octupolar
      structures show considerably improved linear and nonlinear photophysical
      properties under one- and two-photon irradiation conditions compared to the
      corresponding monomers. Photolysis of the three acetate derivatives shows strong
      structure dependency: whereas irradiation of the 6- and 7-aminoquinoline
      derivatives resulted in fast intramolecular cyclization and only trace amounts of
      fragmentation products, the 8-aminoquinoline derivative afforded clean and
      selective photolysis, with a sequential release of their acetate groups
      (deltau[730]=0.67 GM).

PMID- 29046862
TI  - Chemoenzymatic Synthesis in Flow Reactors: A Rapid and Convenient Preparation of
      Captopril.
AB  - The chemoenzymatic flow synthesis of enantiomerically pure captopril, a widely
      used antihypertensive drug, is accomplished starting from simple, inexpensive,
      and readily available reagents. The first step is a heterogeneous biocatalyzed
      regio- and stereoselective oxidation of cheap prochiral 2-methyl-1,3-propandiol,
      performed in flow using immobilized whole cells of Acetobacter aceti MIM 2000/28,
      thus avoiding the use of aggressive and environmentally harmful chemical
      oxidants. The isolation of the highly hydrophilic intermediate (R)-3-hydroxy-2
      methylpropanoic acid is achieved in-line by using a catch-and-release strategy.
      Then, three sequential high-throughput chemical steps lead to the isolation of
      captopril in only 75 min. In-line quenching and liquid-liquid separation enable
      breaks in the workflow and other manipulations to be avoided.

PMID- 29046863
TI  - CO2 Cycloaddition to Epoxides by using M-DABCO Metal-Organic Frameworks and the
      Influence of the Synthetic Method on Catalytic Reactivity.
AB  - A series of high-quality M2(BDC)2(DABCO) metal-organic frameworks (abbreviated as
      M-DABCO; M=Zn, Co, Ni, Cu; BDC=1,4-benzene dicarboxylate; DABCO=1,4
      diazabicyclo[2.2.2]octane), were synthesized by using a solvothermal (SV) method,
      and their catalytic activity for the cycloaddition of CO2 to epoxides in the
      absence of a co-catalyst or solvent was demonstrated. Of these metal-organic
      frameworks (MOFs), Zn-DABCO exhibited very high activity and nearly complete
      selectivity under moderate reaction conditions. The other members of this MOF
      series (Co-DABCO, Ni-DABCO, and Cu-DABCO) displayed lower activity in the given
      sequence. Samples of Zn-DABCO, Co-DABCO, and Ni-DABCO were recycled at least
      three times without a noticeable loss in catalytic activity. The reaction
      mechanism can be attributed to structural defects along with the acid-base
      bifunctional characteristics of these MOFs. Moreover, we illustrate that the
      synthetic method of M-DABCO influences the yield of the reaction. In addition to
      the SV method, Zn-DABCO was synthesized by using spray drying due to its
      industrial attractiveness. It was found that the synthesis procedure clearly
      influenced the crystal growth and thus the physicochemical properties, such as
      surface area, pore volume, and gas adsorption, which in turn affected the
      catalytic performance. The results clarified that although different synthetic
      methods can produce isostructural MOFs, the application of MOFs, especially as
      catalysts, strongly depends on the crystal morphology and textural properties
      and, therefore, on the synthesis method.

PMID- 29046864
TI  - Corrigendum: Synthesis of Metal Nanoparticles and Metal Fluoride Nanoparticles
      from Metal Amidinate Precursors in 1-Butyl-3-Methylimidazolium Ionic Liquids and
      Propylene Carbonate.
AB  - [This corrects the article DOI: 10.1002/open.201600105.].

PMID- 29046865
TI  - Measuring Aggregation of Events about a Mass Using Spatial Point Pattern Methods.
AB  - We present a methodology that detects event aggregation about a mass surface
      using 3-dimensional study regions with a point pattern and a mass present. The
      Aggregation about a Mass function determines aggregation, randomness, or
      repulsion of events with respect to the mass surface. Our method closely
      resembles Ripley's K function but is modified to discern the pattern about the
      mass surface. We briefly state the definition and derivation of Ripley's K
      function and explain how the Aggregation about a Mass function is different. We
      develop the novel function according to the definition: the Aggregation about a
      Mass function times the intensity is the expected number of events within a
      distance h of a mass. Special consideration of edge effects is taken in order to
      make the function invariant to the location of the mass within the study region.
      Significance of aggregation or repulsion is determined using simulation
      envelopes. A simulation study is performed to inform researchers how the
      Aggregation about a Mass function performs under different types of aggregation.
      Finally, we apply the Aggregation about a Mass function to neuroscience as a
      novel analysis tool by examining the spatial pattern of neurotransmitter release
      sites as events about a neuron.

PMID- 29046866
TI  - Transforming Mutations of Jak3 (A573V and M511I) Show Differential Sensitivity to
      Selective Jak3 Inhibitors.
AB  - BACKGROUND: A medical need exists for successfully treating patients afflicted
      with leukemia and especially those that relapse and ultimately become refractory
      to front line chemotherapies. Leukemia cases are particularly high within
      Hispanic populations where this disease is among the most frequently occurring
      cancer. A possible cause is somatic mutations in Janus tyrosine kinase (Jak3).
      Fourteen somatic mutations have been reported in Jak3, including M511I and A573V,
      from patients with various forms of leukemia. While several of these Jak3
      mutations have been shown to possess transforming ability in cell lines, whether
      these mutations are susceptible to Jak3 selective inhibitors remains less clear.
      METHODS: The IL-3 dependent pro-B cell line Ba/F3 was virally transduced with
      plasmids encoding GFP and different mutant forms of Jak3, some of which conferred
      IL-3 independence. Sensitivity to pre-clinical and clinical Jak3 selective
      inhibitors was assessed for cellular viability and growth. RESULTS: Two Jak3
      mutations conferred IL-3 independent growth in Ba/F3 cells. However, the level of
      drug sensitivity varied with respect to Jak3 inhibitors NC1153, CP-690,550, and
      EP-009. CONCLUSION: Jak3 inhibitors CP-690,550 and NC1153 showed efficacy in
      reducing viability of Ba/F3 cells transformed with mutant forms of Jak3, thus
      providing new therapeutic strategies to treat these types of cancer.

PMID- 29046867
TI  - Use of Multicenter Data in a Large Cancer Registry for Evaluation of Outcome and
      Implementation of Novel Concepts.
AB  - Large clinical cancer registries (CCRs) in Germany shall be strengthened by the
      German Social Code Book V (SGB V) and implemented until the end of 2017. There
      are currently several large cancer registries that support clinical data for
      outcome analysis and knowledge acquisition. The various examples of the Munich
      Cancer Registry outlined in this paper present many-sided possibilities using and
      analyzing registry data. The main objective of population-based cancer
      registration within a defined area and the performance of outcomes research is to
      provide feedback regarding the results to the broad public, the reporting
      doctors, and the scientific community. These tasks determine principles of
      operation and data usage by CCRs. Each clinical department delivers its own
      findings and applied therapy. The compilation of these data in CCRs provides
      information on patient progress through the regional network of medical care and
      delivers meaningful information on the course of oncological diseases. Successful
      implementation of CCRs allows for presenting the statistical outcomes of health
      care delivery, improving the quality of care within the region, accelerating the
      process of implementing innovative therapies, and generating new hypotheses as a
      stimulus for research activities.

PMID- 29046868
TI  - Inactive trans-Sialidase Expression in iTS-null Trypanosoma cruzi Generates
      Virulent Trypomastigotes.
AB  - Disclosing virulence factors from pathogens is required to better understand the
      pathogenic mechanisms involved in their interaction with the host. In the case of
      Trypanosoma cruzi several molecules are associated with virulence. Among them,
      the trans-sialidase (TS) has arisen as one of particular relevance due to its
      effect on the immune system and involvement in the interaction/invasion of the
      host cells. The presence of conserved genes encoding for an inactive TS (iTS)
      isoform is puzzlingly restricted to the genome of parasites from the Discrete
      Typing Units TcII, TcV, and TcVI, which include highly virulent strains. Previous
      in vitro results using recombinant iTS support that this isoform could play a
      different or complementary pathogenic role to that of the enzymatically active
      protein. However, direct evidence involving iTS in in vivo pathogenesis and
      invasion is still lacking. Here we faced this challenge by transfecting iTS-null
      parasites with a recombinant gene that allowed us to follow its expression and
      association with pathological events. We found that iTS expression improves
      parasite invasion of host cells and increases their in vivo virulence for mice as
      shown by histopathologic findings in heart and skeletal muscle.

PMID- 29046869
TI  - Staphylococcus aureus Alpha-Toxin Induces the Formation of Dynamic Tubules
      Labeled with LC3 within Host Cells in a Rab7 and Rab1b-Dependent Manner.
AB  - Staphylococcus aureus is a pathogen that causes severe infectious diseases that
      eventually lead to septic and toxic shock. S. aureus infection is characterized
      by the production of virulence factors, including enzymes and toxins. After
      internalization S. aureus resides in a phagosome labeled with Rab7 protein. Here,
      we show that S. aureus generates tubular structures marked with the small GTPases
      Rab1b and Rab7 and by the autophagic protein LC3 at early times post-infection.
      As shown by live cell imaging these tubular structures are highly dynamic,
      extend, branch and grow in length. We have named them S. aureus induced filaments
      (Saf). Furthermore, we demonstrate that the formation of these filaments depends
      on the integrity of microtubules and the activity of the motor protein Kinesin-1
      (Kif5B) and the Rab-interacting lysosomal protein (RILP). Our group has
      previously reported that alpha-hemolysin, a secreted toxin of S. aureus, is
      responsible of the activation of the autophagic pathway induced by the bacteria.
      In the present report, we demonstrate that the autophagic protein LC3 is
      recruited to the membrane of S. aureus induced filaments and that alpha-hemolysin
      is the toxin that induces Saf formation. Interestingly, increasing the levels of
      intracellular cAMP significantly inhibited Saf biogenesis. Remarkably in this
      report we show the formation of tubular structures that emerge from the S. aureus
      containing phagosome and that these tubules generation seems to be required for
      efficient bacteria replication.

PMID- 29046871
TI  - Correction to: Does this patient have Pheochromocytoma? a systematic review of
      clinical signs and symptoms.
AB  - [This corrects the article DOI: 10.1186/s40200-016-0226-x.].

PMID- 29046870
TI  - Salmonella Populations inside Host Cells.
AB  - Bacteria of the Salmonella genus cause diseases ranging from gastroenteritis to
      life-threatening typhoid fever and are among the most successful intracellular
      pathogens known. After the invasion of the eukaryotic cell, Salmonella exhibits
      contrasting lifestyles with different replication rates and subcellular
      locations. Although Salmonella hyper-replicates in the cytosol of certain host
      cell types, most invading bacteria remain within vacuoles in which the pathogen
      proliferates at moderate rates or persists in a dormant-like state. Remarkably,
      these cytosolic and intra-vacuolar intracellular lifestyles are not mutually
      exclusive and can co-exist in the same infected host cell. The mechanisms that
      direct the invading bacterium to follow the cytosolic or intra-vacuolar "pathway"
      remain poorly understood. In vitro studies show predominance of either the
      cytosolic or the intra-vacuolar population depending on the host cell type
      invaded by the pathogen. The host and pathogen factors controlling phagosomal
      membrane integrity and, as consequence, the egress into the cytosol, are
      intensively investigated. Other aspects of major interest are the host defenses
      that may affect differentially the cytosolic and intra-vacuolar populations and
      the strategies used by the pathogen to circumvent these attacks. Here, we
      summarize current knowledge about these Salmonella intracellular subpopulations
      and discuss how they emerge during the interaction of this pathogen with the
      eukaryotic cell.

PMID- 29046872
TI  - Swallow-Breath Interaction and Phase of Respiration with Swallow during Non
      Nutritive Suck in Infants Affected by Neonatal Abstinence Syndrome.
AB  - BACKGROUND: The development of suck-swallow-breath rhythms during non-nutritive
      suck (NNS) may be an indicator of neurologic integrity. We have described swallow
      breath (SwBr) interaction and phase of respiration (POR) with swallow during NNS
      in low-risk preterm (LRP) infants. NNS in infants with neonatal abstinence
      syndrome (NAS) has not been described with our method. METHOD: Suckle, swallow,
      thoracic motion, and nasal airflow were measured during NNS in 10 infants with
      NAS and 12 unaffected infants (control). Logistic regression models were fit to
      describe the three types of SwBr and five types of POR in terms of the
      independent variables (gender, gestational age, birth weight, postmenstrual age,
      weeks postfirst nipple feed and swallows per study). We also compared the NAS
      group to 16 LRP infants. RESULTS: In the NAS group, there were 94 swallows in 18
      studies. In the control group, there were 94 swallows in 12 studies. There were
      statistical differences between groups for all three types of SwBr. The
      distribution of SwBr in NAS was similar to LRP infants with NAS having fewer
      swallows with attenuated respiration and more with central apnea. For POR, there
      were few differences. Over time, the distribution of SwBr in NAS infants
      approaches that of control infants. DISCUSSION: Variability in SwBr and POR
      during NNS may represent neurologic dysfunction in infants with NAS.
      Specifically, term infants with NAS display an immature pattern of SwBr making
      them more similar to preterm infants, rather than a unique pathology. The
      distribution of SwBr and POR in NAS infants becomes more like term infants,
      possibly representing catch-up development as the NAS symptoms resolve.
      CONCLUSION: SwBr in babies with NAS is different from that of unaffected term
      infants, actually being similar to preterm infants. Infants with NAS exhibit a
      dysmature pattern of NNS development which resolves over time.

PMID- 29046873
TI  - Embryonic Stem Cell-Like Subpopulations in Venous Malformation.
AB  - BACKGROUND: Venous malformation (VM) consists of a network of ectatic anomalous
      thin-walled venous channels. A role for an activating TIE2 mutation in the
      development of the dilated luminal vessels in VM, and its proposed involvement of
      embryonic stem cells (ESCs), led us to investigate the expression of ESC markers
      in subcutaneous VM (SCVM) and intramuscular VM (IMVM). METHODS: Formalin-fixed
      paraffin-embedded sections of SCVM from seven patients and IMVM samples from
      seven patients were analyzed for the expression of Nanog, pSTAT3, OCT4, SOX2,
      SALL4, and CD44, using 3,3'-diaminobenzidine (DAB) immunohistochemical (IHC)
      staining. All these samples did not express lymphatic marker D2-40. NanoString
      mRNA analysis and RT-PCR were performed on snap-frozen samples of SCVM (n = 3)
      and IMVM (n = 3) from the respective original cohorts of patients included in DAB
      IHC staining. To confirm co-expression of two proteins, immunofluorescent (IF)
      IHC staining on two representative samples of IMVM and SCVM samples from the
      original cohorts of patients included for DAB IHC staining was performed.
      RESULTS: DAB IHC staining demonstrated expression of all of the above ESC markers
      in both SCVM and IMVM samples. IF IHC staining showed that these markers were
      localized to the endothelium within these lesions and that Nanog, pSTAT3, SOX2,
      and CD44 were also expressed by cells outside of the endothelium. NanoString mRNA
      analysis confirmed transcription activation of pSTAT3, OCT4, and CD44. RT-qPCR
      confirmed transcription activation of Nanog, SOX2, and SALL4. CONCLUSION: Our
      findings support the presence of two ESC-like subpopulations, one within and one
      outside of the endothelium, of both SCVM and IMVM. Given that the endothelial ESC
      like subpopulation expresses the more primitive marker, OCT4, it is exciting to
      speculate that they give rise to the non-endothelial subpopulation.

PMID- 29046874
TI  - Biochemical Pathways of Sarcopenia and Their Modulation by Physical Exercise: A
      Narrative Review.
AB  - Aging is a complex process characterized by progressive multisystem derangement
      predisposing individuals to increased risk of developing negative health
      outcomes. Sarcopenia is the age-related decline of muscle mass and
      function/strength and represents a highly prevalent correlate of aging. Several
      factors have been indicated to play a role in the onset and progression of
      sarcopenia; however, its pathophysiology is still unclear. Physical exercise is
      to date one of the few strategies able to improve muscle health in old age
      through multiple metabolic and transcriptional adaptations. Although the benefits
      of different exercise modalities on the function and structure of aged myocytes
      is acknowledged, the cellular and molecular mechanisms underlying such effects
      are not yet fully identified. Here, we briefly overview the current knowledge on
      the biochemical pathways associated with the onset and progression of sarcopenia.
      We subsequently describe the effects of exercise on relevant signaling pathways
      involved in sarcopenia pathophysiology.

PMID- 29046876
TI  - The emergence of multidrug-resistant clone ST664 Pseudomonas aeruginosa in a
      referral burn hospital, Isfahan, Iran.

PMID- 29046875
TI  - Asymmetric RNA Distribution among Cells and Their Secreted Exosomes: Biomedical
      Meaning and Considerations on Diagnostic Applications.
AB  - Over the past few years, exosomes and their RNA cargo have been extensively
      studied because of the fascinating biological roles they play in cell-to-cell
      communication, including the signal exchange among cancer, stromal, and immune
      cells, leading to modifications of tumor microenvironment. RNAs, especially
      miRNAs, stored within exosomes, seem to be among the main determinants of such
      signaling: their sorting into exosomes appears to be cell-specific and related to
      cellular physiopathology. Accordingly, the identification of exosomal miRNAs in
      body fluids from pathological patients has become one of the most promising
      activity in the field of biomarker discovery. Several analyses on the qualitative
      and quantitative distribution of RNAs between cells and their secreted exosomes
      have given rise to questions on whether and how accurately exosomal RNAs would
      represent the transcriptomic snapshot of the physiological and pathological
      status of secreting cells. Although the exact molecular mechanisms of sorting
      remain quite elusive, many papers have reported an evident asymmetric
      quantitative distribution of RNAs between source cells and their exosomes. This
      phenomenon could depend both on passive and active sorting mechanisms related to:
      (a) RNA turnover; (b) maintaining the cytoplasmic miRNA:target equilibrium; (c)
      removal of RNAs not critical or even detrimental for normal or diseased cells.
      These observations represent very critical issues in the exploitation of exosomal
      miRNAs as cancer biomarkers. In this review, we will discuss how much the
      exosomal and corresponding donor cell transcriptomes match each other, to better
      understand the actual reliability of exosomal RNA molecules as pathological
      biomarkers reflecting a diseased status of the cells.

PMID- 29046878
TI  - Determination of the Proteomic Response to Lapatinib Treatment using a
      comprehensive and reproducible ion-current-based proteomics strategy.
AB  - Lapatinib, a small molecule tyrosine kinase inhibitor is currently used in the
      treatment of HER2-positive breast cancer. The aim of this study was to further
      understanding of lapatinib response for the development of novel treatment
      lapatinib-focussed treatment strategies. HER2-overexpressing SKBR3 breast cancer
      cells were treated with lapatinib for 12 hours and the resultant proteome
      analyzed by a comprehensive ion-current-based LC-MS strategy. Among the 1224
      unique protein identified from SKBR3 cell lysates, 67 showed a significant change
      in protein abundance in response to lapatinib. Of these, CENPE a centromeric
      protein with increased abundance, was chosen for further validation. Knockdown
      and inhibition of CENPE demonstrated that CENPE enhances SKBR3 cell survival in
      the presence of lapatinib. Based on this study, CENPE inhibitors may warrant
      further investigation for use in combination with lapatinib.

PMID- 29046877
TI  - Effect of carotenoids dietary supplementation on macular function in diabetic
      patients.
AB  - BACKGROUND: Diabetic retinopathy is a major cause of visual impairment and
      blindness among working-age people worldwide. The aim of our study was to
      investigate the effects of a carotenoid supplementation on retinal thickness and
      macular function of patients with diabetes using optical coherence tomography
      (OCT) and multifocal electroretinography (mfERG). METHODS: A retrospective study
      of one hundred and twenty eyes of sixty patients age between 40 and 60 years with
      non-insulin dependent type 2 diabetes mellitus without diabetic retinopathy who
      underwent OCT and mfERG and took vitamin supplements for a period of two years.
      Patients received a carotenoid supplement containing lutein (10 mg), zeaxanthin
      (2 mg) and meso-zeaxanthin (10 mg) once a day for two years. The thickness of the
      fovea was evaluated using OCT and the macular function was tested by mfERG.
      RESULTS: OCT showed an increase in the central foveal thickness and mfERG
      revealed increased retinal response density within the central 13 degrees 
      surrounding the fovea (rings 1 to 3) at two years after the onset of carotenoids
      supplement intake. CONCLUSION: The use of carotenoid supplements may be of
      benefit for improving visual function of type 2 diabetes patients. However,
      further study is needed to assess the treatment's long-term efficacy.

PMID- 29046879
TI  - Impaired synaptic function is linked to cognition in Parkinson's disease.
AB  - OBJECTIVE: Cognitive impairment is frequent in Parkinson's disease, but the
      underlying mechanisms are insufficiently understood. Because cortical metabolism
      is reduced in Parkinson's disease and closely associated with cognitive
      impairment, and CSF amyloid-beta species are reduced and correlate with
      neuropsychological performance in Parkinson's disease, and amyloid-beta release
      to interstitial fluid may be related to synaptic activity; we hypothesize that
      synapse dysfunction links cortical hypometabolism, reduced CSF amyloid-beta, and
      presynaptic deposits of alpha-synuclein. We expect a correlation between
      hypometabolism, CSF amyloid-beta, and the synapse related-markers CSF neurogranin
      and alpha-synuclein. METHODS: Thirty patients with mild-to-moderate Parkinson's
      disease and 26 healthy controls underwent a clinical assessment, lumbar puncture,
      MRI, 18F-fludeoxyglucose-PET, and a neuropsychological test battery (repeated for
      the patients after 2 years). RESULTS: All subjects had CSF amyloid-beta 1-42
      within normal range. In Parkinson's disease, we found strong significant
      correlations between cortical glucose metabolism, CSF Abeta, alpha-synuclein, and
      neurogranin. All PET CSF biomarker-based cortical clusters correlated strongly
      with cognitive parameters. CSF neurogranin levels were significantly lower in
      mild-to-moderate Parkinson's disease compared to controls, correlated with
      amyloid-beta and alpha-synuclein, and with motor stage. There was little change
      in cognition after 2 years, but the cognitive tests that were significantly
      different, were also significantly associated with cortical metabolism. No such
      correlations were found in the control group. INTERPRETATION: CSF Abeta, alpha
      synuclein, and neurogranin concentrations are related to cortical metabolism and
      cognitive decline. Synaptic dysfunction due to Abeta and alpha-synuclein
      dysmetabolism may be central in the evolution of cognitive impairment in
      Parkinson's disease.

PMID- 29046881
TI  - NMNAT3 is protective against the effects of neonatal cerebral hypoxia-ischemia.
AB  - OBJECTIVE: To determine whether the NAD+ biosynthetic protein, nicotinamide
      mononucleotide adenylyltransferase-3 (NMNAT3), is a neuroprotective inducible
      enzyme capable of decreasing cerebral injury after neonatal hypoxia-ischemia (H
      I) and reducing glutamate receptor-mediated excitotoxic neurodegeneration of
      immature neurons. METHODS: Using NMNAT3-overexpressing mice we investigated
      whether increases in brain NMNAT3 reduced cerebral tissue loss following H-I. We
      then employed biochemical methods from injured neonatal brains to examine the
      inducibility of NMNAT3 and the mechanism of NMNAT3-dependent neuroprotection.
      Using AAV8-mediated vectors for in vitro neuronal NMNAT3 knockdown, we then
      examine the endogenous role of this protein on immature neuronal survival prior
      and following NMDA receptor-mediated excitotoxicity. RESULTS: NMNAT3 mRNA and
      protein levels increased after neonatal H-I. In addition, NMNAT3 overexpression
      decreased cortical and hippocampal tissue loss 7 days following injury. We
      further show that the NMNAT3 neuroprotective mechanism involves a decrease in
      calpastatin degradation, and a decrease in caspase-3 activity and calpain
      mediated cleavage. Conversely, NMNAT3 knockdown of cortical and hippocampal
      neurons in vitro caused neuronal degeneration and increased excitotoxic cell
      death. The neurodegenerative effects of NMNAT3 knockdown were counteracted by
      exogenous upregulation of NMNAT3. CONCLUSIONS: Our observations provide new
      insights into the neuroprotective mechanisms of NMNATs in the injured developing
      brain, adding NMNAT3 as an important neuroprotective enzyme in neonatal H-I via
      inhibition of apoptotic and necrotic neurodegeneration. Interestingly, we find
      that endogenous NMNAT3 is an inducible protein important for maintaining the
      survival of immature neurons. Future studies aimed at uncovering the mechanisms
      of NMNAT3 upregulation and neuroprotection may offer new therapies against the
      effects of hypoxic-ischemic encephalopathy.

PMID- 29046880
TI  - Improved diagnosis of Parkinson's disease from a detailed olfactory phenotype.
AB  - OBJECTIVE: To assess the predictive potential of the complete response pattern
      from the University of Pennsylvania Smell Identification Test for the diagnosis
      of Parkinson's disease. METHODS: We analyzed a large dataset from the Arizona
      Study of Aging and Neurodegenerative Disorders, a longitudinal
      clinicopathological study of health and disease in elderly volunteers. Using the
      complete pattern of responses to all 40 items in each subject's test, we built
      predictive models of neurodegenerative disease, and we validated these models out
      of sample by comparing model predictions against postmortem pathological
      diagnosis. RESULTS: Consistent with anatomical considerations, we found that the
      specific test response pattern had additional predictive power compared with a
      conventional measure - total test score - in Parkinson's disease, but not
      Alzheimer's disease. We also identified specific test questions that carry the
      greatest predictive power for disease diagnosis. INTERPRETATION: Olfactory
      ability has typically been assessed with either self-report or total score on a
      multiple choice test. We showed that a more accurate clinical diagnosis can be
      made using the pattern of responses to all the test questions, and validated this
      against the "gold standard" of pathological diagnosis. Information in the
      response pattern also suggests specific modifications to the standard test that
      may optimize predictive power under the typical clinical constraint of limited
      time. We recommend that future studies retain the individual item responses for
      each subject, and not just the total score, both to enable more accurate
      diagnosis and to enable additional future insights.

PMID- 29046882
TI  - Biased numerical cognition impairs economic decision-making in Parkinson's
      disease.
AB  - OBJECTIVE: Previous findings suggest a context-dependent bihemispheric allocation
      of numerical magnitude. Accordingly, we predicted that lateralized motor symptoms
      in Parkinson's disease (PD), which reflect hemispheric asymmetries, would induce
      systematic lateralized biases in numerical cognition and have a subsequent
      influence on decision-making. METHODS: In 20 PD patients and matched healthy
      controls we assessed numerical cognition using a number-pair bisection and random
      number generation task. Decision-making was assessed using both the dictator game
      and a validated questionnaire. RESULTS: PD patients with predominant right-sided
      motor symptoms exhibited pathological biases toward smaller numerical magnitudes
      and formulated less favorable prosocial choices during a neuroeconomics task
      (i.e., dictator game). Conversely, patients with left-sided motor symptoms
      exhibited pathological biases toward larger numerical magnitudes and formulated
      more generous prosocial choices. Our account of context-dependent hemispheric
      allocation of numerical magnitude in PD was corroborated by applying our data to
      a pre-existing computational model and observing significant concordance.
      Notably, both numerical biasing and impaired decision-making were correlated with
      motor asymmetry. INTERPRETATION: Accordingly, motor asymmetry and functional
      impairment of cognitive processes in PD can be functionally intertwined. To
      conclude, our findings demonstrate context-dependent hemispheric allocation and
      encoding of numerical magnitude in PD and how biases in numerical magnitude
      allocation in Parkinsonian patients can correspondingly impair economic decision
      making.

PMID- 29046883
TI  - Human neural stem cell transplantation into the corpus callosum of Alzheimer's
      mice.
AB  - The hippocampus has been the target of stem cell transplantations in preclinical
      studies focused on Alzheimer's disease, with results showing improvements in
      histological and behavioral outcomes. The corpus callosum is another structure
      that is affected early in Alzheimer's disease. Therefore, we hypothesize that
      this structure is a novel target for human neural stem cell transplantation in
      transgenic Alzheimer's disease mouse models. This study demonstrates the
      feasibility of targeting the corpus callosum and identifies an effective
      immunosuppression regimen for transplanted neural stem cell survival. These
      results support further preclinical development of the corpus callosum as a
      therapeutic target in Alzheimer's disease.

PMID- 29046884
TI  - Selective intrathecal enrichment of G1m1-positive B cells in multiple sclerosis.
AB  - Immunoglobulin gamma (IgG) heavy chain genes are associated with susceptibility
      to multiple sclerosis (MS) and IgG levels in the cerebrospinal fluid (CSF).
      However, how these variants are implicated in disease mechanisms remains unknown.
      Here, we show that proliferating plasmablasts expressing the G1m1 allotype of
      IgG1 are selectively enriched in CSF of G1m1/G1m3 heterozygous MS patients,
      whereas plasmablasts expressing either G1m1 or G1m3 are evenly distributed in
      blood. Moreover, there was a preferential intrathecal synthesis of oligoclonal
      IgG1 of the G1m1 allotype in heterozygous patients, whereas controls with Lyme
      neuroborreliosis displayed oligoclonal IgG1 of both allotypes. This points to a
      disease-specific mechanism involved in B-cell establishment within the central
      nervous system in MS.

PMID- 29046885
TI  - Comment on: Extra-virgin olive oil ameliorates cognition and neuropathology of
      the 3xTg mice: role of autophagy.

PMID- 29046886
TI  - Reply to comment: Extravirgin olive oil ameliorates cognition and neuropathology
      of the 3xTg mice.

PMID- 29046887
TI  - Erratum: Selected missense mutations impair frataxin processing in Friedreich
      ataxia.
AB  - [This corrects the article DOI: 10.1002/acn3.433.].

PMID- 29046888
TI  - Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid
      Withdrawal.
AB  - The rate of opioid overdose continues to rise, necessitating improved treatment
      options. Current therapeutic approaches rely on administration of either a
      blocking agent, such as naloxone, or chronic treatment with replacement drugs,
      including methadone and/or buprenorphine. Recent findings suggest that males and
      females respond to these treatments uniquely. In an effort to better understand
      this sex-specific variation in treatment efficacy, we investigated the effects of
      acute opioid withdrawal in male and female rats using 18FDG and microPET. These
      data demonstrate that acute opioid withdrawal produces metabolic alterations in
      brain regions associated with reward and drug dependence, namely corpus striatum,
      thalamic nuclei, septum, and frontal cortex. Furthermore, certain changes are
      unique to males. Specifically, males demonstrated increased metabolism in the
      anterior cingulate cortex and the ventral hippocampus (CA3) following acute
      opioid withdrawal. If males and females exhibit sex-specific changes in regional
      brain metabolism following acute opioid withdrawal, then perhaps it is not
      surprising that they respond to treatment differently.

PMID- 29046889
TI  - Whispering-gallery-mode emission from biological luminescent protein microcavity
      assemblies.
AB  - Fluorescence and bioluminescence are widely used to study biological systems from
      molecular to whole organism level. However, their broadband emission is often a
      bottleneck for sensitive spectral measurements and multiplexing. To overcome the
      limitation, the emitters can be coupled with optical cavity modes to generate
      narrowband spectral features. Here we demonstrate several types of emitter
      resonator complexes made of fluorescent or bioluminescent proteins and
      artificially or naturally formed optical resonators. We engineered cells to
      express green fluorescent protein (GFP) fused with ABHD5, which binds to oil or
      lipid droplets supporting whispering gallery modes (WGM). The genetically
      integrated complexes feature well-defined WGM spectral peaks. We measured WGM
      peaks from GFP-coated BaTiO3 beads (2.56 MUm in diameter) during mitosis.
      Finally, we demonstrate cavity-enhanced bioluminescence using luciferase-coated
      beads and biochemical excitation. The ability to tailor spontaneous emission by
      cavity resonance inside biological systems should have applications in biological
      sensing, imaging and cell tagging.

PMID- 29046890
TI  - A comparison of passive and active estimates of sleep in a cohort with
      schizophrenia.
AB  - Sleep abnormalities are considered an important feature of schizophrenia, yet
      convenient and reliable sleep monitoring remains a challenge. Smartphones offer a
      novel solution to capture both self-reported and objective measures of sleep in
      schizophrenia. In this three-month observational study, 17 subjects with a
      diagnosis of schizophrenia currently in treatment downloaded Beiwe, a platform
      for digital phenotyping, on their personal Apple or Android smartphones. Subjects
      were given tri-weekly ecological momentary assessments (EMAs) on their own
      smartphones, and passive data including accelerometer, GPS, screen use, and
      anonymized call and text message logs was continuously collected. We compare the
      in-clinic assessment of sleep quality, assessed with the Pittsburgh Sleep
      Questionnaire Inventory (PSQI), to EMAs, as well as sleep estimates based on
      passively collected accelerometer data. EMAs and passive data classified 85%
      (11/13) of subjects as exhibiting high or low sleep quality compared to the in
      clinic assessments among subjects who completed at least one in-person PSQI.
      Phone-based accelerometer data used to infer sleep duration was moderately
      correlated with subject self-assessment of sleep duration (r = 0.69, 95% CI 0.23
      0.90). Active and passive phone data predicts concurrent PSQI scores for all
      subjects with mean average error of 0.75 and future PSQI scores with a mean
      average error of 1.9, with scores ranging from 0-14. These results suggest sleep
      monitoring via personal smartphones is feasible for subjects with schizophrenia
      in a scalable and affordable manner.

PMID- 29046891
TI  - Neurobiological Models of the Impact of Adversity on Education.
AB  - Poverty and exposure to adversity have been linked with decreased educational
      success. Various environmental and neurobiological pathways have been proposed
      for these associations, however, existing models have several clear drawbacks.
      Here we outline existing models, and propose an alternate model linking exposure
      to adverse experiences in childhood to education success. Specifically, we
      propose that measured dimensions of experience (e.g., decreased cognitive
      enrichment or increased exposure to violence), instead of named exposures (e.g.,
      poverty) impact neurobiology through neurodevelopmental processes of
      neuroplasticity. Our model results in testable hypotheses and clear intervention
      strategies. We predict that exposure to trauma will have a distinct
      neurobiological impact from exposure to a lack of cognitive stimulation and that
      these distinct exposures will benefit from different interventions. Specificity
      in this arena is thus likely to better support educational achievement for
      disadvantaged children.

PMID- 29046892
TI  - Intramolecular Photogeneration of a Tyrosine Radical in a Designed Protein.
AB  - Long-distance biological electron transfer occurs through a hopping mechanism and
      often involves tyrosine as a high potential intermediate, for example in the
      early charge separation steps during photosynthesis. Protein design allows for
      the development of minimal systems to study the underlying principles of complex
      systems. Herein, we report the development of the first ruthenium-linked designed
      protein for the photogeneration of a tyrosine radical by intramolecular electron
      transfer.

PMID- 29046893
TI  - The measurement of the surface energy of solids using a laboratory drop tower.
AB  - This work presents a technique for the study and measurement of the interfacial
      energies of solid-liquid-gas systems. The instrument and the evaluation method
      for the measurements obtained by it, allow the analysis of the energy changes of
      sessile drops submitted to microgravity. A mathematical model based on the
      thermodynamic of wetting is applied to evaluate the interfacial energies as a
      function of the drop shape changes due to the effect of the release of
      gravitation during the experiment. The presented model bases on the thermodynamic
      equilibrium of the interfaces and not on the balance of bi-dimensional tensors on
      the contour line. For this reason, the model does not follow Young's equation as
      the current surface wetting characterization techniques usually do.

PMID- 29046895
TI  - Compression for Similarity Identification: Computing the Error Exponent.
AB  - We consider the problem of compressing discrete memoryless data sequences for the
      purpose of similarity identification, first studied by Ahlswede et al. (1997). In
      this setting, a source sequence is compressed, where the goal is to be able to
      identify whether the original source sequence is similar to another given
      sequence (called the query sequence). There is no requirement that the source
      will be reproducible from the compressed version. In the case where no false
      negatives are allowed, a compression scheme is said to be reliable if the
      probability of error (false positive) vanishes as the sequence length grows. The
      minimal compression rate in this sense, which is the parallel of the classical
      rate distortion function, is called the identification rate. The rate at which
      the error probability vanishes is measured by its exponent, called the
      identification exponent (which is the analog of the classical excess distortion
      exponent). While an information-theoretic expression for the identification
      exponent was found in past work, it is uncomputable due to a dependency on an
      auxiliary random variable with unbounded cardinality. The main result of this
      paper is a cardinality bound on the auxiliary random variable in the
      identification exponent, thereby making the quantity computable (solving the
      problem that was left open by Ahlswede et al.). The new proof technique relies on
      the fact that the Lagrangian in the optimization problem (in the expression for
      the exponent) can be decomposed by coordinate (of the auxiliary random variable).
      Then a standard Caratheodory - style argument completes the proof.

PMID- 29046894
TI  - Fatty Acid-Mimetic Micelles for Dual Delivery of Antigens and Imidazoquinoline
      Adjuvants.
AB  - Vaccine design has undergone a shift towards the use of purified protein subunit
      vaccines, which offer increased safety and greater control over antigen
      specificity, but at the expense of immunogenicity. Here we report the development
      of a new polymer-based vaccine delivery platform engineered to enhance immunity
      through the co-delivery of protein antigens and the Toll-like receptor 7 (TLR7)
      agonist imiquimod (IMQ). Owing to the preferential solubility of IMQ in fatty
      acids, a series of block copolymer micelles with a fatty acid-mimetic core
      comprising lauryl methacrylate (LMA) and methacrylic acid (MAA), and a
      poly(ethylene glycol) methyl ether methacrylate (PEGMA) corona decorated with
      pyridyl disulfide ethyl methacrylate (PDSM) moieties for antigen conjugation were
      synthesized via reversible addition-fragmentation chain transfer (RAFT)
      polymerization. Carriers composed of 50 mole% LMA (LMA50) demonstrated the
      highest IMQ loading (2.2 w/w%) and significantly enhanced the immunostimulatory
      capacity of IMQ to induce dendritic cell maturation and proinflammatory cytokine
      production. Conjugation of a model antigen, ovalbumin (OVA), to the corona of IMQ
      loaded LMA50 micelles enhanced in vitro antigen uptake and cross-presentation on
      MHC class I (MHC-I). A single intranasal (IN) immunization of mice with carriers
      co-loaded with IMQ and OVA elicited significantly higher pulmonary and systemic
      CD8+ T cell responses and increased serum IgG titer relative to a soluble
      formulation of antigen and adjuvant. Collectively, these data demonstrate that
      rationally designed fatty acid-mimetic micelles enhance intracellular antigen and
      IMQ delivery and have potential as synthetic vectors for enhancing the
      immunogenicity of subunit vaccines.

PMID- 29046896
TI  - GeneComp, a new reference-based compressor for SAM files.
AB  - The affordability of DNA sequencing has led to unprecedented volumes of genomic
      data. These data must be stored, processed, and analyzed. The most popular format
      for genomic data is the SAM format, which contains information such as alignment,
      quality values, etc. These files are large (on the order of terabytes), which
      necessitates compression. In this work we propose a new reference-based
      compressor for SAM files, which can accommodate different levels of compression,
      based on the specific needs of the user. In particular, the proposed compressor
      GeneComp allows the user to perform lossy compression of the quality scores,
      which have been proven to occupy more than half of the compressed file (when
      losslessly compressed). We show that the proposed compressor GeneComp overall
      achieves better compression ratios than previously proposed algorithms when
      working on lossless mode.

PMID- 29046897
TI  - Compressing Tabular Data via Pairwise Dependencies.

PMID- 29046898
TI  - The role of the paravertebral muscles in adolescent idiopathic scoliosis
      evaluated by temporary paralysis.
AB  - BACKGROUND: Muscle imbalance has been suggested as implicated in the pathology of
      adolescent idiopathic scoliosis (AIS). The specific "pathomechanic" role of the
      paravertebral muscles as being scoliogenic (inducing scoliosis) or counteracting
      scoliosis in the initial development and maintenance of this spinal deformity has
      yet to be clarified in humans. In the present study, we investigated the
      radiographic changes of temporal paralysis using botulinum toxin A as localized
      injection therapy (ITB) in the psoas major muscle in AIS patients. METHODS: Nine
      patients with AIS were injected one time with ITB using ultrasonic and EMG
      guidance in the selected spine muscles. Radiographic and clinical examinations
      were performed before and 6 weeks after the injection. Primary outcome parameters
      of radiological changes were analyzed using Wilcoxon signed-rank test and
      binomial test, and secondary outcome parameters of short- and long-term clinical
      effects were obtained. RESULTS: Significant radiological corrective changes were
      seen in the frontal plane in the thoracic and lumbar spine as well as significant
      derotational corrective change in the lumbar spine according to Cobb's angle
      measurements and to Nash and Moe's classification, respectively. No serious
      adverse events were detected at follow-up. CONCLUSIONS: In conclusion, this study
      demonstrated that the psoas major muscle do play a role into the pathology in
      adolescent idiopathic scoliosis by maintaining the curvature of the lumbar spine
      and thoracic spine. TRIAL REGISTRATION: EudraCT number 2008-004584-19.

PMID- 29046899
TI  - Marketing activities of vape shops across racial/ethnic communities.
AB  - INTRODUCTION: There has been a surge in the number of vape shops in the USA.
      Research on the marketing practices of e-cigarette manufacturers is scarce and
      even less known are the practices of vape shop retailers. Past research on
      tobacco marketing has shown differences in the amount and content of marketing
      material, based on a community's demographic profile. This study examined
      marketing strategies in vape shops and explored differences among vape shops
      located in communities that differ by ethnic composition. METHODS: Data was
      gathered in 2014 from a pilot-study on vape shops (n=77) in Los Angeles, which
      documented the characteristics of shops through employee interviews and in-store
      observations. Data were collected from shops located in communities that were
      predominantly, African-American (n=20), Hispanic (n=17), Korean (n=18), or non
      Hispanic White (n=22). RESULTS: Sixty-one percent of vape shops had
      advertisements (print ads and posters) for e-cigarettes and 84% offered
      discounts. Vape shops in Hispanic communities were more likely to have ethnic
      specific marketing material compared to shops in other communities. All the shops
      provided customers with free samples, however those in Korean and non-Hispanic
      White communities had a significantly higher prevalence of customer accessible
      free samples. CONCLUSIONS: Vape shop marketing practices differed by ethnic
      community. A large majority of shops provided free samples to their customers, a
      practice which is now banned by the FDA. It will be important to monitor how vape
      shops will adjust their marketing strategy because of this ban. Future research
      should expand on the findings presented here to provide regulators with further
      crucial information.

PMID- 29046900
TI  - US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell
      Transplant in Philadelphia Chromosome Positive ALL.
AB  - This multicenter trial was conducted to determine whether the addition of
      dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant
      (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic
      leukemia (ALL) was feasible. Patients >= 18 and <= 60 years of age with newly
      diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose
      cytarabine and methotrexate with dasatinib. Patients with an available matched
      sibling or unrelated donor underwent an allogeneic HCT in first complete
      remission (CR1) followed by daily dasatinib starting from day 100. Others
      received maintenance therapy with vincristine and prednisone for 2 years and
      dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years
      (range, 20 - 60) and median WBC at presentation of 10 * 109/L (range, 1 - 410 *
      109/L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count
      recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months
      (range, 9 - 63). For the overall population, overall survival (OS), event-free
      survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and
      62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%,
      respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time
      to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and
      0.037, respectively) for the transplanted patients. Addition of dasatinib to
      chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants
      further testing.

PMID- 29046901
TI  - ?
AB  - The median life expectancy of population among industrialized countries has
      dramatically expanded in recent years. On the other hand, the risk of developing
      cancer increases with age.The treatment for gynaecological malignancies is well
      defined with respect to the surgery, radiation treatment and chemotherapy.
      However, elderly patients receives substandard treatment when compared to the
      younger people, generally due to the presence of associated medical conditions.
      The assessment of the co-morbidity is an important aspect of the surgical
      decision-making process.Maximal cytoreductive surgery is one of the most powerful
      determinants of survival in patients with FIGO stage III and IV ovarian cancer.
      Unfortunately, older patients underwent fewer operations as compared with those
      of their younger counterparts However, in recent years, new developments in the
      fields of anesthesiology, perioperative care, and surgical techniques have
      modified the picture and several studies confirm the feasibility of optimal
      cytoreduction with a complication rate similar to younger patients.Elderly
      patients may tolerate well surgical procedures within acceptable postoperative
      morbidity, a length of hospital stay and a need for intensive care quite similar
      to that of younger patients.

PMID- 29046903
TI  - FOD Restoration for Enhanced Mapping of White Matter Lesion Connectivity.
AB  - To achieve improved understanding of white matter (WM) lesions and their effect
      on brain functions, it is important to obtain a comprehensive map of their
      connectivity. However, changes of the cellular environment in WM lesions
      attenuate diffusion MRI (dMRI) signals and make the robust estimation of fiber
      orientation distributions (FODs) difficult. In this work, we integrate techniques
      from image inpainting and compartment modeling to develop a novel method for
      enhancing FOD estimation in WM lesions from multi-shell dMRI, which is becoming
      increasingly popular with the success of the Human Connectome Project (HCP). By
      using FODs estimated from normal WM as the boundary condition, our method
      iteratively cycles through two key steps: diffusion-based inpainting and FOD
      reconstruction with compartment modeling for the successful restoration of FODs
      in WM lesions. In our experiments, we carry out extensive simulations to
      quantitatively demonstrate that our method outperforms a state-of-the-art method
      in angular accuracy and compartment parameter estimation. We also apply our
      method to multi-shell imaging data from 23 multiple sclerosis (MS) patients and
      one LifeSpan subject of HCP with WM lesion. We show that our method achieves
      superior performance in mapping the connectivity of WM lesions with FOD-based
      tractography.

PMID- 29046902
TI  - Holistic Mapping of Striatum Surfaces in the Laplace-Beltrami Embedding Space.
AB  - In brain shape analysis, the striatum is typically divided into three parts: the
      caudate, putamen, and accumbens nuclei for its analysis. Recent connectivity and
      animal studies, however, indicate striatum-cortical inter-connections do not
      always follow such subdivisions. For the holistic mapping of striatum surfaces,
      conventional spherical registration techniques are not suitable due to the large
      metric distortions in spherical parameterization of striatal surfaces. To
      overcome this difficulty, we develop a novel striatal surface mapping method
      using the recently proposed Riemannian metric optimization techniques in the
      Laplace-Beltrami (LB) embedding space. For the robust resolution of sign
      ambiguities in the LB spectrum, we also devise novel anatomical contextual
      features to guide the surface mapping in the embedding space. In our experimental
      results, we compare with spherical registration tools from FreeSurfer and FSL to
      demonstrate that our novel method provides a superior solution to the striatal
      mapping problem. We also apply our method to map the striatal surfaces from 211
      subjects of the Human Connectome Project (HCP), and use the surface maps to
      construct a cortical connectivity atlas. Our atlas results show that the striato
      cortical connectivity is not distinctive according to traditional structural
      subdivision of the striatum, and further confirms the holistic approach for
      mapping striatal surfaces.

PMID- 29046904
TI  - Label-Informed Non-negative Matrix Factorization with Manifold Regularization for
      Discriminative Subnetwork Detection.
AB  - In this paper, we present a novel method for obtaining a low dimensional
      representation of a complex brain network that: (1) can be interpreted in a
      neurobiologically meaningful way, (2) emphasizes group differences by accounting
      for label information, and (3) captures the variation in disease
      subtypes/severity by respecting the intrinsic manifold structure underlying the
      data. Our method is a supervised variant of non-negative matrix factorization
      (NMF), and achieves dimensionality reduction by extracting an orthogonal set of
      subnetworks that are interpretable, reconstructive of the original data, and also
      discriminative at the group level. In addition, the method includes a manifold
      regularizer that encourages the low dimensional representations to be smooth with
      respect to the intrinsic geometry of the data, allowing subjects with similar
      disease-severity to share similar network representations. While the method is
      generalizable to other types of non-negative network data, in this work we have
      used structural connectomes (SCs) derived from diffusion data to identify the
      cortical/subcortical connections that have been disrupted in abnormal
      neurological state. Experiments on a traumatic brain injury (TBI) dataset
      demonstrate that our method can identify subnetworks that can reliably classify
      TBI from controls and also reveal insightful connectivity patterns that may be
      indicative of a biomarker.

PMID- 29046905
TI  - The controversial role of forkhead box F2 (FOXF2) transcription factor in breast
      cancer.
AB  - Deregulating the subcellular localization, functions and expression of Forkhead
      box (FOX) transcription factors that are critically involved in embryonic
      development and multiple biological processes is known to result in the
      development and progression of diseases, in particular cancer. Human FOXF
      transcription factors, including FOXF1 and FOXF2, are a subfamily of the FOX gene
      family. The recent findings from ours and others have linked FOXF2 to breast
      cancer development and progression. Our studies have shown that FOXF2 acts as a
      tumor-suppressive inhibitor of DNA replication in luminal and HER2-positive
      breast cancers and as an oncogenic activator of the epithelial-mesenchymal
      transition (EMT) in triple-negative/basal-like breast cancers (TN/BLBC),
      suggesting that FOXF2 plays a dual role in breast cancer. However, studies from
      Feng's research group have pointed out an opposite role of FOXF2 in TN/BLBC,
      which acts as an inhibitor of the EMT and as a promoter of cell proliferation in
      TN/BLBC. These discrepancies between our and Feng's studies have caused
      controversy in the role of FOXF2 in breast cancer. This article reviews both
      studies and discusses what causes might have led to these inconsistencies as well
      as what future experiments are needed to solve this debate.

PMID- 29046906
TI  - Target and identify: triazene linker helps identify azidation sites of labelled
      proteins via click and cleave strategy.
AB  - A method for identifying probe modification of proteins via tandem mass
      spectrometry was developed. Azide bearing molecules are immobilized on
      functionalised sepharose beads via copper catalysed Huisgen-type click chemistry
      and selectively released under acidic conditions by chemical cleavage of the
      triazene linkage. We applied this method to identify the modification site of
      targeted-diazotransfer on BirA.

PMID- 29046907
TI  - Bladder regeneration in a canine model using a bladder acellular matrix loaded
      with a collagen-binding bFGF.
AB  - Bladder reconstruction remains challenging for urological surgery due to lack of
      suitable regenerative scaffolds. In a previous study, we had used a collagen
      binding basic fibroblast growth factor (CBD-bFGF) to bind bFGF to the collagen
      scaffold, which could promote bladder regeneration in rats. However, the limited
      graft size in rodent models cannot provide enough evidence to demonstrate the
      repair capabilities of this method for severely damaged bladders in humans or
      large animals. In this study, the CBD-bFGF was used to activate a bladder
      acellular matrix (BAM) scaffold, and the CBD-bFGF/BAM functional scaffold was
      assessed in a canine model with a large segment defect (half of the entire
      bladder was resected). The results demonstrated that the functional biomaterials
      could promote bladder smooth muscle, vascular, and nerve regeneration and improve
      the function of neobladders. Thus, the CBD-bFGF/BAM functional scaffold may be a
      promising biomaterial for bladder reconstruction.

PMID- 29046908
TI  - Phenolic compounds, antioxidant activity, antiproliferative activity and
      bioaccessibility of Sea buckthorn (Hippophae rhamnoides L.) berries as affected
      by in vitro digestion.
AB  - Phenolics, antioxidant and antiproliferative properties of Sea buckthorn berries
      were evaluated using a simulated in vitro digestion and compared with a chemical
      extraction method. Digested samples were subjected to antiproliferation
      evaluation against human liver, breast and colon cancer cells. Furthermore, the
      bioaccessibility of digested berries was evaluated using a Caco-2 cell culture
      model. Results revealed that after enzymatic digestion the phenolic compounds
      were quite different from the chemical extracts, more flavonoid aglycones were
      released, whereas less total phenolics, phenolic acids and flavonoid glycosides
      were detected. Although the extracellular antioxidant activity of the digesta was
      lower than that of extracts, the cellular antioxidant activity (CAA) and
      antiproliferative effects of berries were significantly enhanced by digestion.
      This was attributed to their higher flavonoid aglycone content and could be
      verified by testing individual active compounds, suggesting that the cellular
      uptake of samples might be improved, which was also certified by the Caco-2 cell
      uptake model. The digested samples showed an almost 5-fold cellular accumulative
      amount of isorhamnetin than pure isorhamnetin, which was attributed to the
      significant down regulation of the mRNA expression level of efflux transporters
      MRP2 and P-gp. This finding indicated that the digestion enhanced the
      bioaccessibility of bioactive compounds of berries.

PMID- 29046916
TI  - Enhancement of charge transfer between graphene and donor-pi-acceptor molecule
      for ultrahigh sensing performance.
AB  - In this work, we report the formation of a supramolecular assembly of graphene
      with a donor-pi-acceptor (D-pi-A) molecule to detect low concentration NO2. 5
      Aminonaphthalene-1-sulfonic acid (ANS) was used herein to pi-pi stack with
      reduced graphene oxide (rGO), the resulting pi-conjugated bridge being linked by
      a donor unit (-NH2) and an acceptor unit (-SO3H). The prepared ANS-rGO shows the
      highest response (Ra/Rg = 13.2 to 10 ppm NO2) so far among the reported organic
      molecule modified graphene materials, and excellent selectivity and reliable
      reversibility at room temperature. Furthermore, as revealed through the charge
      density difference calculation, it is the effective enhancement of charge
      transfer between ANS and graphene that should be responsible for the sharp
      improvement of NO2 gas response of the material. Thus, for the first time, we
      demonstrate that supramolecular assembly of a D-pi-A molecule and graphene
      provides a facile and effective approach to fabrication of high performance
      graphene-based gas sensors.

PMID- 29046917
TI  - Effects of an injectable functionalized self-assembling nanopeptide hydrogel on
      angiogenesis and neurogenesis for regeneration of the central nervous system.
AB  - Brain injury is a devastating medical condition and represents a major health
      problem. Tissue and organ reconstruction have been regarded as promising
      therapeutic strategies. Here, we propose a regenerative methodology focusing on
      the provision of functionalized nanopeptide scaffolds to facilitate angiogenesis
      and neurogenesis at the brain injury site. The peptide RADA16-SVVYGLR undergoes
      self-assembly to construct an interconnected network with intertwining
      nanofibers, and can be controlled to display various physicochemical properties
      by the adjustment of microenvironmental factors such as pH and ion concentration.
      Such scaffolds can support endothelial cells to form tube-like structures and
      neural stem cells to survive and proliferate. In an in vivo zebrafish brain
      injury model, sprouting angiogenesis and developmental neurogenesis were
      achieved, and functional recovery of the severed optic tectum was enhanced in
      RADA16-SVVYGLR hydrogel-implanted zebrafish. This nanopeptide hydrogel was non
      toxic to zebrafish embryos during early developmental stages. This angiogenic
      self-assembling peptide hydrogel had programmable physical properties, good
      biocompatibility, and regenerative ability for functional recovery in the injured
      brain. We suggest that functionalized self-assembling peptides encapsulated with
      neural stem cells or used alone could be an attractive and effective therapeutic
      modality for brain injury and diseases (e.g., trauma, stroke, tumor, degenerative
      neurological disorders, etc.).

PMID- 29046918
TI  - Flow diverter treatment of cerebral blister aneurysms.
AB  - PURPOSE: Blood blister-like aneurysms (BBA) are small, friable, broad-based
      aneurysms that represent high risk for rerupture. Treatment of BBA is
      challenging, and may include surgical wrapping, clipping, multiple overlapping
      stents, and/or coiling. Flow diversion is a rapidly evolving treatment strategy
      for intracranial aneurysms, but the evidence for its use in cases of BBA is
      scarce. METHODS: A retrospective review of flow-diverter-treated, ruptured BBA
      cases at our tertiary care institution was undertaken. Clinical, imaging,
      procedural, and mid-term follow-up data on the patients were collected. RESULTS:
      Eight patients underwent flow-diverter stent treatment for ruptured BBA. Median
      age at time of treatment was 49 years (interquartile range [IQR] 42-57) with five
      females (62.5%). The most common location of the BBA was the supraclinoid segment
      of the internal carotid artery. The median Hunt-Hess score was 2 (IQR 1.7-3.2).
      All patients were treated with dual anti-platelet therapy. Good clinical outcomes
      (modified Rankin score 0-2) were seen in 6/7 (85.7%) patients with available
      follow-up at 1 year. Complete occlusion of the aneurysm on latest angiogram (7)
      or MRI (1) was seen in 6/8 (75%) patients (at a median of 8 months). No patient
      had rerupture, retreatment, or recurrence of the aneurysm. CONCLUSION: Flow
      diverter stents may be a feasible treatment option for BBAs. They offer high
      occlusion and low retreatment rates with good mid-term outcomes, but the long
      term efficacy remains unknown. Also, dual anti-platelet therapy in the acute
      ruptured setting can be challenging.

PMID- 29046919
TI  - Female gonadal shielding with automatic exposure control increases radiation
      risks.
AB  - BACKGROUND: Gonadal shielding remains common, but current estimates of gonadal
      radiation risk are lower than estimated risks to colon and stomach. A female
      gonadal shield may attenuate active automatic exposure control (AEC) sensors,
      resulting in increased dose to colon and stomach as well as to ovaries outside
      the shielded area. OBJECTIVE: We assess changes in dose-area product (DAP) and
      absorbed organ dose when female gonadal shielding is used with AEC for pelvis
      radiography. MATERIALS AND METHODS: We imaged adult and 5-year-old equivalent
      dosimetry phantoms using pelvis radiograph technique with AEC in the presence and
      absence of a female gonadal shield. We recorded DAP and mAs and measured organ
      absorbed dose at six internal sites using film dosimetry. RESULTS: Female gonadal
      shielding with AEC increased DAP 63% for the 5-year-old phantom and 147% for the
      adult phantom. Absorbed organ dose at unshielded locations of colon, stomach and
      ovaries increased 21-51% in the 5-year-old phantom and 17-100% in the adult
      phantom. Absorbed organ dose sampled under the shield decreased 67% in the 5-year
      old phantom and 16% in the adult phantom. CONCLUSION: Female gonadal shielding
      combined with AEC during pelvic radiography increases absorbed dose to organs
      with greater radiation sensitivity and to unshielded ovaries. Difficulty in
      proper use of gonadal shields has been well described, and use of female gonadal
      shielding may be inadvisable given the risks of increasing radiation.

PMID- 29046920
TI  - Commentary on: Suburethral sling procedures in the United States: complications,
      readmission, and reoperation.

PMID- 29046922
TI  - Selection and identification of transferrin receptor-specific peptides as
      recognition probes for cancer cells.
AB  - Since the transferrin receptor (CD71 or TFRC) is known to be highly expressed in
      numerous cancers, CD71 has become an attractive target in cancer research.
      Acquiring specific molecular probes for CD71, such as small molecular ligands,
      aptamers, peptides, or antibodies, is of great importance for cancer cell
      recognition and capture. In this work, we chose CD71 as the target for phage
      display, and after four rounds of positive selection and one round of negative
      selection, the specific phage library was enriched. After verification and
      sequence analysis, six peptides were identified to be able to bind to CD71 with
      high specificity. The specific recognition of the CD71-positive cells was
      confirmed by flow cytometry and confocal microscopy. Competition experiments
      demonstrated that peptide Y1 and transferrin (TF) were bound to distinct sites on
      CD71, indicating that peptide Y1 could replace TF as a potential probe for cell
      imaging and drug delivery, thus avoiding competition by endogenous TF and side
      effects. Graphical abstract Six peptides were successfully isolated using in
      vitro biopanning against CD71 with high specificity and affinity. Peptides Y1 and
      Y2 would be powerful tools in biosensors and biomedicine due to their unique
      properties.

PMID- 29046923
TI  - The capillary gap sampler, a new microfluidic platform for direct coupling of
      automated solid-phase microextraction with ESI-MS.
AB  - A new technology for rapid, automated coupling of solid-phase microextraction and
      mass spectrometry is introduced. Use of a so-called capillary gap sampler for
      automated solid-phase microextraction and direct delivery of the extracted
      analytes to a mass spectrometer provides certain advantages over existing
      technologies: coupling of the capillary gap sampler to a mass spectrometer offers
      quick, automated, and site-specific extraction from very low volume samples. High
      stability, reusability, and repeatability were achieved through systematic
      optimization. Diazepam, oxazepam, and nordiazepam were used as test compounds in
      all experiments. The ability of the sampler to extract benzodiazepines from human
      plasma (limit of detection 0.3 MUg/mL) in the therapeutic range was confirmed. A
      linear dynamic range from 1 to 1000 ng/mL for all three analytes was found. The
      relative standard deviation of 20 extractions was between 11% and 17%, for
      oxazepam, nordiazepam, and diazepam, indicating acceptable repeatability of the
      method. Graphical Abstract Schematic of the desorption step inside the liquid
      bridge formed between two capillaries in thecapillary gap sampler.

PMID- 29046921
TI  - Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of
      browning in cultured human adipocytes: a randomised, controlled trial in humans.
AB  - AIMS/HYPOTHESIS: Increasing brown adipose tissue (BAT) activity is a possible
      therapeutic strategy to increase energy expenditure and glucose and lipid
      clearance to ameliorate obesity and associated comorbidities. The
      thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in
      preclinical experimental models but whether these actions extend to humans in
      vivo is unknown. The aim of this study was to determine the effect of
      pioglitazone treatment on adipocyte browning and adaptive thermogenesis in
      humans. METHODS: We first examined whether pioglitazone treatment of cultured
      human primary subacromioclavicular-derived adipocytes induced browning. Then, in
      a blinded, placebo-controlled, parallel trial, conducted within the Baker
      Institute clinical research laboratories, 14 lean male participants who were free
      of cardiometabolic disease were randomised to receive either placebo (lactose; n
      = 7, age 22 +/- 1 years) or pioglitazone (45 mg/day, n = 7, age 21 +/- 1 years)
      for 28 days. Participants were allocated to treatments by Alfred Hospital staff
      independent from the study via electronic generation of a random number sequence.
      Researchers conducting trials and analysing data were blind to treatment
      allocation. The change in cold-stimulated BAT activity, assessed before and after
      the intervention by [18F]fluorodeoxyglucose uptake via positron emission
      tomography/computed tomography in upper thoracic and cervical adipose tissue, was
      the primary outcome measure. Energy expenditure, cardiovascular responses, core
      temperature, blood metabolites and hormones were measured in response to acute
      cold exposure along with body composition before and after the intervention.
      RESULTS: Pioglitazone significantly increased in vitro browning and adipogenesis
      of adipocytes. In the clinical trial, cold-induced BAT maximum standardised
      uptake value was significantly reduced after pioglitazone compared with placebo (
      57 +/- 6% vs -12 +/- 18%, respectively; p < 0.05). BAT total glucose uptake
      followed a similar but non-significant trend (-50 +/- 10% vs -6 +/- 24%,
      respectively; p = 0.097). Pioglitazone increased total and lean body mass
      compared with placebo (p < 0.05). No other changes between groups were detected.
      CONCLUSIONS/INTERPRETATION: The disparity in the actions of pioglitazone on BAT
      between preclinical experimental models and our in vivo human trial highlight the
      imperative to conduct human proof-of-concept studies as early as possible in BAT
      research programmes aimed at therapeutic development. Our clinical trial findings
      suggest that reduced BAT activity may contribute to weight gain associated with
      pioglitazone and other TZDs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02236962
      FUNDING: This work was supported by the Diabetes Australia Research Program and
      OIS scheme from the Victorian State Government.

PMID- 29046924
TI  - Liquid chromatography-mass spectrometry with triazole-bonded stationary phase for
      N-methyl-D-aspartate receptor-related amino acids: development and application in
      microdialysis studies.
AB  - We aimed to monitor changes in the levels of amino acid neurotransmitters or
      neuromodulators simultaneously at the synaptic clefts of experimental animals. We
      developed a method for the simultaneous determination of the levels of amino
      acids, such as D-Ser, Gly, and L-Glu, which were involved in neurotransmission
      via the N-methyl-D-aspartate (NMDA) receptor, and other protein-constituted amino
      acids in a rat brain microdialysis (MD) sample. We used a liquid chromatography
      mass spectrometry (LC-MS)/MS device equipped with a triazole-bonded column. The
      determination was achieved without using stable isotope-labeled compounds. We
      instead used suitable amino acid analogues as internal standards (ISs). We
      examined various analyte-IS combinations to improve reproducibility. We found a
      positive correlation (r = 0.720, **p < 0.0001) between relative standard
      deviation (%) of the area ratio and the analyte-IS retention time differences.
      Using the proposed method, we were able to accurately analyze trace amounts of
      amino acids in MD samples using ISs that were structurally similar to the
      analytes. Furthermore, we observed that the peripheral administration of S-methyl
      L-cysteine, which was an inhibitor of the amino acid transporter Asc-1, caused
      some amino acid level changes in the rat brain. The proposed LC-MS/MS method can
      be applied in vivo to study the effects of novel therapeutic agents with
      monitoring the levels of amino acid neuromodulators, such as Glu, Gly, GABA, and
      D-Ser, in the brain. Graphical abstract LC-MS/MS analysis of amino acid
      enantiomers in microdialysis samples from rat striatum using triazole-bonded
      stationary phase.

PMID- 29046925
TI  - [Clinical anamnestic characteristics in neurological work-related medical
      rehabilitation : Necessity for a qualitative identification of severe
      restrictions of work ability].
AB  - BACKGROUND: Severe restrictions of work ability (SRWA) as a condition for
      participation in neurological work-related medical rehabilitation (WMR) have not
      been adequately described up to now. Similarly, the applicability of the
      screening instrument SIMBO-C for evaluating SRWA in neurological rehabilitation
      has not yet been answered conclusively. OBJECTIVE: Determination of clinical and
      anamnestic characteristics of neurological SRWA and assessment of the
      applicability of the screening instrument SIMBO-C in neurological WMR. MATERIAL
      AND METHODS: For the identification of SRWA clinical and anamnestic
      characteristics of 344 rehabilitants were routinely collected. The clinically and
      anamnestically determined SRWA was described quantitatively and content
      analytically and correlated with SIMBO-C. RESULTS: Of the rehabilitants 66%
      exhibited SRWA. Apart from the established characteristics of SRWA further person
      and disease-specific factors were found. The SIMBO-C score was significantly
      higher in the group with SRWA compared to the group without SRWA (45.6 +/- 18.9
      vs. 31.5 +/- 12.5, p < 0.001); however, 31% of the group with SRWA and 50% of the
      group without SRWA demonstrated a SIMBO-C score <= 36 points and thereby a large
      overlap. The profile of the clinical and anamnestic characteristics in the group
      with SRWA was homogeneous, regardless of the SIMBO-C score. CONCLUSION: The
      characteristics of neurological SRWA are mainly qualitatively shaped and may only
      partly be identified by SIMBO-C. A combined quantitative and qualitative approach
      is necessary in neurological WMR.

PMID- 29046926
TI  - ?

PMID- 29046928
TI  - What future for the myocardial sympathetic innervation imaging?

PMID- 29046929
TI  - Improved fruiting of the straw mushroom (Volvariella volvacea) on cotton waste
      supplemented with sodium acetate.
AB  - Compared with controls, treatment of the cultivation substrate for Volvariella
      volvacea with 0.02% NaAc at the "spraying water" stage increased the number of
      fruiting body primordia by 280, the mushroom yield by 16.25%, the number of
      fruiting bodies by 35.57%, and the biological efficiency by 16.28%. The average
      single mushroom weight increased by 19.33%, but there was no significant
      difference between treatments and controls. A correlation analysis revealed a
      significant (p < 0.05) positive correlation between the total yield and the
      number of fruiting bodies. Comparisons of the cost and profit values for the
      sodium acetate-treated and untreated groups revealed that the former generated a
      higher income for the grower. Our data indicate that sodium acetate treatment is
      a promising new method for increasing V. volvacea yields. A possible mechanism
      whereby sodium acetate increased the mushroom yield is discussed.

PMID- 29046930
TI  - Asfotase alfa treatment for 1 year in a 16 year-old male with severe childhood
      hypophosphatasia.
AB  - We describe the clinical outcome of asfotase alfa therapy in a 16-year-old boy
      with severe childhood hypophosphatasia (HPP), who began therapy at age 15 years.
      The patient was diagnosed with HPP at age 2 years when he presented with genu
      varum and premature loss of primary teeth. He had a history of multiple fractures
      requiring 16 orthopedic surgeries with rod and pin placement in his lower
      extremities. He had chronic skeletal pain and used cane to ambulate with great
      difficulty. His height Z score at age 15 years was - 5. He had severe scoliosis
      and deformity of both legs. Bone radiograph showed hypomineralization and
      characteristic "tongues" of radiolucency in the distal radius and ulna. His serum
      alkaline phosphatase level was stable, with elevated serum pyridoxal 5'-phosphate
      and urine phosphoethanolamine, consistent with HPP. He was started on asfotase
      alfa 2 mg/kg given subcutaneously thrice weekly. He had marked clinical
      improvement in mobility with no report of pain after 3 months of treatment. At 6
      month, he walked without cane and participated in outdoor activities with peers.
      Bone radiograph at 6 months showed striking improvement in previous radiolucent
      areas. At 9 months, his annualized growth velocity was 9.5 cm/year, while growth
      velocity of arm span was 12 cm/year. However, at 12 months, he was noted to have
      worsening scoliosis from 60 degrees before therapy to 110 degrees, with a slight
      decrease in height, necessitating a spinal fusion surgery. In conclusion,
      treatment with asfotase alfa significantly improved physical function, pain,
      overall quality of life, and skeletal radiographic findings in this patient.
      Close monitoring for progression of scoliosis in adolescents with HPP treated
      with asfotase alfa is recommended.

PMID- 29046927
TI  - FDG PET/CT radiomics for predicting the outcome of locally advanced rectal
      cancer.
AB  - PURPOSE: The aim of this study was to investigate the prognostic value of
      baseline 18F-FDG PET/CT textural analysis in locally-advanced rectal cancer
      (LARC). METHODS: Eighty-six patients with LARC underwent 18F-FDG PET/CT before
      treatment. Maximum and mean standard uptake values (SUVmax and SUVmean),
      metabolic tumoral volume (MTV), total lesion glycolysis (TLG), histogram
      intensity features, as well as 11 local and regional textural features, were
      evaluated. The relationships of clinical, pathological and PET-derived metabolic
      parameters with disease-specific survival (DSS), disease-free survival (DFS) and
      overall survival (OS) were assessed by Cox regression analysis. Logistic
      regression was used to predict the pathological response by the Dworak tumor
      regression grade (TRG) in the 66 patients treated with neoadjuvant
      chemoradiotherapy (nCRT). RESULTS: The median follow-up of patients was 41
      months. Seventeen patients (19.7%) had recurrent disease and 18 (20.9 %) died,
      either due to cancer progression (n = 10) or from another cause while in complete
      remission (n = 8). DSS was 95% at 1 year, 93% at 2 years and 87% at 4 years.
      Weight loss, surgery and the texture parameter coarseness were significantly
      associated with DSS in multivariate analyses. DFS was 94 % at 1 year, 86 % at 2
      years and 79 % at 4 years. From a multivariate standpoint, tumoral
      differentiation and the texture parameters homogeneity and coarseness were
      significantly associated with DFS. OS was 93% at 1 year, 87% at 2 years and 79%
      after 4 years. cT, surgery, SUVmean, dissimilarity and contrast from the
      neighborhood intensity-difference matrix (contrastNGTDM) were significantly and
      independently associated with OS. Finally, RAS-mutational status (KRAS and NRAS
      mutations) and TLG were significant predictors of pathological response to nCRT
      (TRG 3-4). CONCLUSION: Textural analysis of baseline 18F-FDG PET/CT provides
      strong independent predictors of survival in patients with LARC, with better
      predictive power than intensity- and volume-based parameters. The utility of such
      features, especially coarseness, should be confirmed by larger clinical studies
      before considering their potential integration into decisional algorithms aimed
      at personalized medicine.

PMID- 29046931
TI  - Hip arthroscopy learning curve: a prospective single-surgeon study.
AB  - PURPOSE: Arthroscopy of the hip joint is considered a demanding procedure with
      long learning curve. There are only a few studies that concentrate on this topic.
      This prospective clinical study evaluates the learning curve of the hip
      arthroscopy based on clinical outcomes, surgical time, and complication rate.
      MATERIALS: In this study, we first evaluated 150 hip arthroscopy procedures
      performed by a single surgeon. The patient group consisted of 86 females and 64
      males with mean age 37 years (range 16-69). Study cohorts were divided into
      groups of 50 patients. Surgical time, complication rate and clinical results
      based on NAHS score were recorded for each group. Statistical analysis of
      differences between groups was performed using the ANOVA method and paired t
      test. RESULTS: We found a statistically significant decrease of complication rate
      with more procedures performed. There were significantly better clinical outcomes
      after at least 100 procedures. No difference in surgical time was found, but
      towards the end of the learning curve, more complex procedures were performed.
      The only statistical difference was the portal setup time. The learning curves
      were constructed based on these results. CONCLUSIONS: Hip arthroscopy provides
      very good clinical outcomes if precisely indicated and performed. It is, however,
      a demanding procedure with many possible pitfalls and complications. According to
      our study, at least 100 procedures are needed to gain basic technical and
      indication skills. The presence of a more skilled surgeon in the beginning of the
      learning curve is advised to reduce the complication rate.

PMID- 29046932
TI  - [Postoperative MRI of the ankle].
AB  - CLINICAL/METHODICAL ISSUE: Postoperative imaging of the ankle can be challenging,
      even for the experienced radiologist. Pathological and postoperative changes to
      the primarily complex anatomy of the ankle with its great variety of bone
      structures, tendons, ligaments, and soft tissue in a very limited space may cause
      great difficulty in differentiating underlying pathology from expected
      postoperative changes and artifacts, especially in magnetic resonance imaging
      (MRI). STANDARD RADIOLOGICAL METHODS: Selecting the appropriate radiological
      modality is key to making the correct diagnosis. Therefore, knowledge of the
      initial and current symptoms is just as important as familiarity with the most
      frequently performed operations in the ankle. PRACTICAL RECOMMENDATIONS: This
      article aims to give its reader a summary of the most important and frequently
      performed operation techniques of the ankle and discusses the expected appearance
      and possible complications in postoperative imaging.

PMID- 29046933
TI  - [Regional anesthesia - are the standards changing?]
AB  - Regional anesthesia has undergone many changes over the years and the increasing
      use of ultrasound has certainly played an important role in this. Apart from
      individual case reports in the literature of very different blocking options,
      some new procedures seem to have become established and can be broadly applied.
      Among these are blockades, by which ultrasound-guided injection of local
      anesthetics is carried out in fascial or muscular layers rather than around
      target nerves (e.g. cervical plexus blocks and truncal blocks). In addition, the
      precision with which ultrasound can be used to identify nerve structures led to
      an increasingly better definition of targets exemplified for interscalene or
      femoral nerve blocks. The use of ultrasound also seems to be helpful in the
      performance of neuraxial blocks, particularly in obese patients or patients with
      a difficult anatomy. With the implementation 10 years ago of a registry for
      safety in regional anesthesia and acute pain therapy by the German Society of
      Anesthesiology and Intensive Care Medicine (DGAI) and the Association of German
      Anesthesiologists (BDA), it has been possible to answer important safety
      questions and define protective measures (e.g. tunnelling, antibiotic prophylaxis
      and sedation). Moreover, this registry can be used as a benchmark to compare the
      quality of regional anesthesia in individual hospitals with all other
      participating centers.

PMID- 29046935
TI  - Admission after the gold interval in acute calculous cholecystitis: Should we
      really cool it off?

PMID- 29046934
TI  - [Knowledge of the population about leading symptoms of cardiovascular emergencies
      and the responsibility and accessibility of medical facilities in emergencies :
      Results of the KZEN study in Western Palatinate].
AB  - BACKGROUND: The Westpfalz is a mainly rural region in the southwestern part of
      the German state of Rhineland-Palatinate with 527,000 inhabitants and
      demonstrates a higher than average cardiovascular mortality compared to the rest
      of Germany. The reasons are not known. Our study attempted to investigate whether
      significant deficits in knowledge of the population on cardiovascular
      emergencies, the accessibility of emergency medical services (EMS) or the
      different responsibilities and abilities of the medical facilities could be held
      responsible for this. These factors are of the utmost importance for the timely
      initiation and administration of curative therapeutic strategies. METHODS: We
      conducted standardized telephone interviews with 1126 inhabitants of Westpfalz as
      a representative sample of the population in the study area. The interviewees
      were asked about demographic data, participation in first aid courses, knowledge
      of emergency telephone numbers and the different responsibilities of preclinical
      emergency physicians which are a part of the EMS and the doctor-on-call system
      for non-life-threatening conditions (ABD). Moreover, we asked about the leading
      symptoms of myocardial infarction and stroke. Finally, we enquired how the
      respondents would react in fictitious cardiovascular emergencies. RESULTS: Of the
      participants 651 (57.8%) were female and 475 (42.2%) male. The mean age in our
      study was 51 +/- 18 years and 1002 of the participants (89%) had some formal
      first aid training. The current telephone number of the EMS system (112) was
      known to 29.5% of the interviewees and 15.4% could only recall the old number
      (19222) which is no longer in use. In the case of participants who gave the
      correct telephone number the first aid course took place 10 years ago (median),
      whereas for participants who did not know the correct number, the course dated
      back 15 years (median, p < 0.01). The telephone number 116117 of the ABD, usually
      a family physician, was familiar to only 23 of the people interviewed (2.0%). The
      basic differences in the functions and responsibilities of the ABD and the
      emergency physician within the EMS were known to only 235 participants (20.2%),
      231 (20.5%) were not able to name a single leading symptom of a myocardial
      infarction and 354 did not know a leading symptom (31.4%) of stroke. In the
      fictitious case report of an unconscious patient with respiratory arrest (as a
      sign of cardiac arrest) 96.8% of the interviewees would have correctly informed
      the EMS, for patients with acute coronary syndrome 81.8% and for a stroke patient
      76.8% (cardiac arrest vs. acute coronary syndrome: p < 0.001, cardiac arrest vs.
      stroke: p < 0.001, acute coronary syndrome vs. stroke: p = 0.005). CONCLUSION AND
      RECOMMENDATIONS: A large proportion of the population were found to be ignorant
      about the telephone numbers for medical emergency calls and the different
      functions of the ABD and emergency physicians within the EMS. Moreover, our
      results indicate that a significant percentage of the population would neither be
      in a position to recognize a stroke or myocardial infarction in an emergency
      situation nor be informed enough to communicate with the correct part of the
      emergency system. The association of these deficits with the time elapsed since
      the last first aid course should be reason enough to continuously motivate the
      population, especially at risk patients and their relatives, to repeat such
      courses several times. Furthermore, digital media should be used more intensively
      in providing first aid instructions. In our opinion, this study clearly shows
      that in Germany a uniform number for medical emergency calls is mandatory.

PMID- 29046936
TI  - Localization of helotialean fungi on ectomycorrhizae of Castanopsis cuspidata
      visualized by in situ hybridization.
AB  - Non-ectomycorrhizal fungi that associate with typical ectomycorrhizae often
      remain hidden, and their localization inside ectomycorrhizal (ECM) roots has
      remained uncharacterized. In this study, the fungal community associated with the
      ectomycorrhizae of Castanopsis cuspidata was investigated using a culture
      dependent isolation technique. Additionally, the species composition and
      localization were determined using molecular techniques. The results of the
      isolation and identification of fungal species revealed the predominance of a few
      species belonging to the order Helotiales. Furthermore, the fungal community
      structures were significantly different depending on the taxa of the
      ectomycorrhiza-forming fungi. A taxon-specific probe was developed to analyze the
      localization of one dominant Hyaloscyphaceae (Helotiales) species in ECM tissues
      by in situ hybridization. Hybridization signals were detected on the surface of
      the fungal mantle and around the ECM fungal cells within the mantle. Hyphal
      penetration into ECM hyphal cells of fungal mantles was also observed. Signals
      were not detected in the Hartig net or plant tissues inside the mantle in healthy
      ectomycorrhizae. These findings suggest that the analyzed species interact not
      only with host plant as root endophyte but also directly with the ECM fungi.

PMID- 29046937
TI  - Field evaluation of a novel molluscicide (niclosamidate) against Oncomelania
      hupensis, intermediate host of Schistosoma japonicum.
AB  - The molluscicidal activity of a novel molluscicide (niclosamidate) was evaluated
      in field trials against Oncomelania hupensis, the intermediate host of
      Schistosoma japonicum. The environmental safety of niclosamidate for local fishes
      was also studied under field conditions. The results showed that, at the dosages
      of 8.0 g/m2 and 4.0 g/m3, niclosamidate exhibits highly potent molluscicidal
      activity in the spraying and immersion trials, resulting in mortality rates of up
      to 81.8 and 72.7%, respectively. Its performance seems to be target-specific,
      with good molluscicidal ability observed for Oncomelania hupensis snails, but
      very low toxicity for local fishes and other aquatic organisms. The results
      suggest that niclosamidate can be used as an alternative molluscicide for snail
      control, which would be particularly applicable in semi-commercial or commercial
      aquaculture ponds.

PMID- 29046938
TI  - Is there a negative association between the content of condensed tannins, total
      phenols, and total tannins of tropical plant extracts and in vitro anthelmintic
      activity against Haemonchus contortus eggs?
AB  - In vitro studies using plant extracts suggest a relationship between their
      polyphenol contents and their anthelmintic (AH) activity against Haemonchus
      contortus. High polyphenol content appears to increase the efficacy of plant
      extracts against H. contortus as assessed by the larval exsheathment inhibition
      assay (LEIA) while appearing to reduce the AH efficacy measured using the egg
      hatch assay (EHA). In addition, some plants lack AH activity. Therefore, the
      present study investigated the relationship between the contents of condensed
      tannins (CT), total phenols (TP), and total tannins (TT) in methanol:water
      extracts (70:30) obtained from ten tropical plant species consumed by small
      ruminants as well as their AH activity against H. contortus evaluated by LEIA and
      EHA. Extracts of Acacia collinsii, Lysiloma latisiliquum, Havardia albicans,
      Senegalia gaumeri, Mimosa bahamensis, Piscidia piscipula, Acacia pennatula,
      Gymnopodium floribundum, Leucaena leucocephala, and Bunchosia swartziana were
      examined. Positive correlations were found between the effective concentration
      50% (EC50) (EHA) of extracts and their CT (r = 0.6809, P < 0.05, n = 10) and TP
      (r = 0.9152, P < 0.05, n = 10) content, suggesting that their concentration
      negatively affected AH activity against eggs. Based on the LEIA, there was no
      significant association between the EC50 and the CT, TP, or TT of all extracts
      evaluated. Thus, if sheep and goats consume a complex feed mixture with high
      amounts of CT, TP, and TT, it might be difficult to observe an AH effect against
      H. contortus egg hatching. However, the AH effect upon L3 establishment might be
      feasible.

PMID- 29046940
TI  - Gastric cancer: immunohistochemical classification of molecular subtypes and
      their association with clinicopathological characteristics.
AB  - Gastric cancer is traditionally divided into intestinal and diffuse histological
      subtypes, but recent molecular analyses have led to novel classification
      proposals based on genomic alterations. While the intestinal- and diffuse-type
      tumours are distinguishable from each other at the molecular level, intestinal
      type tumours have more diverse molecular profile. The technology required for
      comprehensive molecular analysis is expensive and not applicable for routine
      clinical diagnostics. In this study, we have used immunohistochemistry and in
      situ hybridisation in molecular classification of gastric adenocarcinomas with an
      emphasis on the intestinal subtype. A tissue microarray consisting of 244 gastric
      adenocarcinomas was constructed, and the tumours were divided into four subgroups
      based on the presence of Epstein-Barr virus, TP53 aberrations and microsatellite
      instability. The intestinal- and diffuse-type tumours were separately examined.
      The distribution of EGFR and HER2 gene amplifications was studied in the
      intestinal-type tumours. Epstein-Barr virus positive intestinal-type tumours were
      more common in male patients (p = 0.035) and most often found in the gastric
      corpus (p = 0.011). The majority of the intestinal-type tumours with TP53
      aberrations were proximally located (p = 0.010). All tumours with microsatellite
      instability showed intestinal-type histology (p = 0.017) and were associated with
      increased overall survival both in the univariate (p = 0.040) and multivariate
      analysis (p = 0.015). In conclusion, this study shows that gastric
      adenocarcinomas can be classified into biologically and clinically different
      subgroups by using a simple method also applicable for clinical diagnostics.

PMID- 29046941
TI  - [Sepsis-3 : What has been confirmed in therapy?]
AB  - Hugo Schottmuller realized already over 100 years ago that sepsis is a syndrome
      that occurs as a consequence of an infection defined by a systemic overreaction
      to a periodic invasion of bacilli. Consistent with this old concept, the term
      "systemic inflammatory response syndrome" (SIRS) was coined about 25 years ago
      and has been regularly used ever since. In 2016, a sepsis task force was formed
      to re-evaluate the current definition on a scientific basis. The task force
      suggested a third definition (sepsis-3) of the disease that now focuses both on
      the pathological host response and on organ dysfunction as obligatory key
      features to diagnose sepsis. In this review article, the definition is explained
      in detail and we summarize the novel international sepsis guideline from 2017
      with personal commentaries.

PMID- 29046942
TI  - Antidepressants and the risk of arrhythmia in elderly affected by a previous
      cardiovascular disease: a real-life investigation from Italy.
AB  - PURPOSE: The study aimed to fill existing knowledge gaps on the safety of
      antidepressant drugs (ADs) by estimating the risk of hospitalization for
      arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs)
      and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV)
      events. METHODS: The cohort was composed by 199,569 individuals aged >= 65 years
      from five Italian healthcare territorial units who were discharged for
      cardiovascular outcomes in the years 2008-2010. The 17,277 patients who
      experienced hospital admission for arrhythmia during follow-up were included as
      cases. Odds of current ADs use among cases (i.e., 14 days before hospital
      admission) was compared with (i) odds of current use of 1:5 matched controls
      (between-patients case-control) and with (ii) odds of previous use during 1:5
      matched control periods (within-patient case-crossover). The risk of arrhythmia
      associated with ADs current use was modelled fitting a conditional logistic
      regression. A set of sensitivity analyses was performed to account for sources of
      systematic uncertainty. RESULTS: Current users of SSRIs and NAAs were at
      increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95%
      confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover
      OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of
      arrhythmia was associated with current use of trazodone (NAA) consistently in
      case-control and case-crossover designs. CONCLUSIONS: Evidence that current use
      of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly
      with CV disease was consistently supplied by two observational approaches.

PMID- 29046944
TI  - Complement functional tests for monitoring eculizumab treatment in patients with
      atypical hemolytic uremic syndrome: an update.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic
      microangiopathy (TMA) characterized by platelet consumption, hemolysis, and organ
      damage. Eculizumab (ECU), a humanized antibody that blocks complement activity,
      has been successfully used in aHUS, but the best treatment schedule is not yet
      clear. METHODS: Here, we report our experience with ECU maintenance treatment and
      the interval between subsequent doses being extended based on global classical
      complement pathway (CCP) activity aimed at <30% for maintaining aHUS into
      remission. RESULTS: We report on 38 patients with aHUS, 13 children, 21 female,
      with a median age of 25.0 years (range 0.5-60) at disease onset treated with ECU
      standard schedule for a median of 2.6 months (range 0.4-24.6). Once stable TMA
      remission was obtained, the interval between ECU doses was extended based on
      complement function, with a target CCP activity of <30%. With this approach, 22
      patients regularly receive ECU infusion every 28 days and 16 every 21. During a
      median observation period on ECU, an extended interval of 26.9 months (range 0.8
      80.9), with a cumulative observation period of 1,208 months, none of the patients
      relapsed. CONCLUSION: Monitoring complement activity allows a safe reduction in
      the frequency of ECU administration in aHUS while keeping the disease in
      remission.

PMID- 29046945
TI  - Cystic renal mass in an infant with significant family history: Answers.

PMID- 29046943
TI  - Congenital pulmonary airway malformations: state-of-the-art review for
      pediatrician's use.
AB  - : Congenital pulmonary airway malformations or CPAM are rare developmental lung
      malformations, leading to cystic and/or adenomatous pulmonary areas. Nowadays,
      CPAM are diagnosed prenatally, improving the prenatal and immediate postnatal
      care and ultimately the knowledge on CPAM pathophysiology. CPAM natural evolution
      can lead to infections or malignancies, whose exact prevalence is still difficult
      to assess. The aim of this "state-of-the-art" review is to cover the recently
      published literature on CPAM management whether the pulmonary lesion was detected
      during pregnancy or after birth, the current indications of surgery or
      surveillance and finally its potential evolution to pleuro-pulmonary blastoma.
      CONCLUSION: Surgery remains the cornerstone treatment of symptomatic lesions but
      the postnatal management of asymptomatic CPAM remains controversial. There are
      pros and cons of surgical resection, as increasing rate of infections over time
      renders the surgery more difficult after months or years of evolution, as well as
      risk of malignancy, though exact incidence is still unknown. What is known: *
      Congenital pulmonary airway malformations (CPAM) are rare developmental lung
      malformations mainly antenatally diagnosed. * While the neonatal management of
      symptomatic CPAM is clear and includes prompt surgery, controversies remain for
      asymptomatic CPAM due to risk of infections and malignancies. What is new: *
      Increased rate of infection over time renders the surgery more difficult after
      months or years of evolution and pushes for recommendation of early elective
      surgery. * New molecular or pathological pathways may help in the distinction of
      type 4 CPAM from type I pleuropulmonary blastoma.

PMID- 29046946
TI  - [Report of the Working Group on Pediatric and Fetal Pathology].

PMID- 29046947
TI  - [Meeting Report of the Working Group on Uropathology of the German Society of
      Pathology].

PMID- 29046949
TI  - Temporal arachnoid cysts: are they congenital?
AB  - CASE REPORT: The authors report two cases of arachnoid cysts (ACs) neither
      detected during pregnancy nor shortly after birth when newborns underwent CT scan
      evaluation after birth head trauma. ACs were diagnosed at 10 months and 6 years,
      respectively. The first one becomes symptomatic, and the other one was
      incidentally found during a head trauma investigation. DISCUSSION: These cases
      give support for the postnatal pathogenesis for some of the assumed congenital
      ACs. We collected data from the literature that supports the acquired hypothesis
      for ACs.

PMID- 29046948
TI  - Planned secondary wound closure at the circular stapler insertion site after
      laparoscopic gastric bypass reduces postoperative morbidity, costs, and hospital
      stay.
AB  - PURPOSE: The aims of the present study were to assess whether planned secondary
      wound closure at the insertion site of the circular stapler reduces wound
      infection rate and postoperative morbidity after laparoscopic Roux-en-Y gastric
      bypass (RYGB) and to identify independent predictive factors increasing the risk
      for wound infections after RYGB. METHODS: This paper is a retrospective single
      center analysis of a prospectively collected database of 1400 patients undergoing
      RYGB surgery in circular technique between June 2000 and June 2016. Planned
      secondary wound closure at the circular stapler introduction site was performed
      at postoperative day 3 in 291 (20.8%) consecutive patients and compared to a
      historical control of 1109 (79.2%) consecutive patients with primary wound
      closure. Independent predictive factors for wound infection were assessed by
      multivariable analysis. RESULTS: Secondary wound closure significantly decreased
      wound infection rate from 9.3% (103/1109) to 1% (3/291) (p < 0.001) leading to a
      shorter hospital stay (mean 9 (SD8) vs. 7 days (SD2), p < 0.001), lower costs (p
      = 0.039), and reduced postoperative morbidity (mean 90-day Comprehensive
      Complication Index (CCI) 7.4 (SD14.0) vs. 5.1 (SD11.1) p = 0.008) when compared
      to primary wound closure. Primary wound closure, dyslipidemia, and preoperative
      gastritis were independent predictive risk factors for developing wound
      infections both in the univariate (p < 0.001; p = 0.048; p = 0.003) and
      multivariable analysis (p < 0.001; p = 0.040; p = 0.012). Further, on
      multivariable analysis, the female gender was a predictive factor (p = 0.034) for
      wound infection development. CONCLUSIONS: Secondary wound closure at the circular
      stapler introduction site in laparoscopic RYGB significantly reduces the overall
      wound infection rate as well as postoperative morbidity, costs, and hospital stay
      when compared to primary wound closure.

PMID- 29046950
TI  - Pediatric neuro-oncology research in the third world.

PMID- 29046951
TI  - Time trends in colorectal cancer early postoperative mortality. A French 25-year
      population-based study.
AB  - BACKGROUND: Postoperative mortality after resection of colorectal cancer is an
      important issue. The aim of this study was to assess early postoperative
      mortality in a well-defined French population. METHODS: Data on 30- and 90-day
      postoperative mortality after resection for colorectal cancer were extracted from
      the digestive cancer registry of Burgundy. Time trends of postoperative mortality
      between 1989 and 2013 were described for the large population. Case-control
      studies (death within 30 or 90 days = cases, alive at 90 days = controls) focused
      on the association between postoperative mortality and surgical approach, obesity
      and other comorbidities over the last [2010-2013] period, using conditional
      logistic regressions. RESULTS: Among the 11,448 concerned patients, 30- and 90
      day postoperative mortalities were 4.9 and 7.2%. Thirty-day operative mortality
      decreased from 7.2% (1989-1993) to 4.4% (2010-2013; p < 0.001) for colon cancer
      and from 4.2 to 3.3% for rectal cancer (NS). Diagnosis before 1997, male gender,
      advanced age, emergency surgery and palliative resection were associated with a
      significantly higher 30- and 90-day mortality rate. The univariate risk of
      mortality was two to three times higher for conventional open laparotomy and
      conversion than for laparoscopy-assisted surgery. The surgical approach was no
      longer significant in multivariate analysis. Emergency surgery and comorbidities
      were associated with higher 30- and 90-day postoperative mortality, whereas
      obesity was not specific. CONCLUSION: Postoperative mortality after colorectal
      resection decreased over time. Surgical approach had no influence on early
      mortality. Improvement in the management of the elderly and patients with
      comorbidities is a challenge to reduce postoperative mortality in the future.

PMID- 29046952
TI  - Evaluation of a visual acuity test using closed Landolt-Cs to determine
      malingering.
AB  - PURPOSE: To evaluate a visual acuity test (VAT) with unexpected optotypes to
      detect malingering. METHODS: We tested two groups. Group 1 consisted of 20
      individuals with normal best corrected visual acuity (BCVA). Group 2 included
      participants with ocular diseases and reduced BCVA. All subjects underwent a VAT
      proposed by Graf and Roesen to assess suspected malingering. This test used 36
      charts with one Landolt-C per page. The first 20 optotypes were Landolt-Cs, while
      at positions 21, 26, 30, and 34 closed rings were presented. The testing distance
      was adapted to 50% of the test person's visual acuity. The test person was
      requested to name the gap direction of the Landolt-C within 3 s. The complete
      testing conversation was recorded digitally to determine response latency for
      each optotype from the audio tracks. RESULTS: The average response time was 0.46
      s in group 1 and 0.45 s in group 2 for the first 20 Landolt-Cs. In both groups
      the response time was significantly extended (p < 0.05) for the first closed ring
      compared to the mean of the first 20 Landolt-Cs, (group 1: 2.9 s; group 2: 2.3
      s). The following three closed rings had also longer response times. However,
      these differences were not significant. CONCLUSIONS: Our results suggest that the
      proposed test may be helpful to evaluate ocular malingering. The testing
      procedure appeared to be feasible and showed good repeatability. The fast
      training effect may be a limitation for malingering detection.

PMID- 29046954
TI  - An eye tracking study of bloodstain pattern analysts during pattern
      classification.
AB  - Bloodstain pattern analysis (BPA) is the forensic discipline concerned with the
      classification and interpretation of bloodstains and bloodstain patterns at the
      crime scene. At present, it is unclear exactly which stain or pattern properties
      and their associated values are most relevant to analysts when classifying a
      bloodstain pattern. Eye tracking technology has been widely used to investigate
      human perception and cognition. Its application to forensics, however, is
      limited. This is the first study to use eye tracking as a tool for gaining access
      to the mindset of the bloodstain pattern expert. An eye tracking method was used
      to follow the gaze of 24 bloodstain pattern analysts during an assigned task of
      classifying a laboratory-generated test bloodstain pattern. With the aid of an
      automated image-processing methodology, the properties of selected features of
      the pattern were quantified leading to the delineation of areas of interest
      (AOIs). Eye tracking data were collected for each AOI and combined with verbal
      statements made by analysts after the classification task to determine the
      critical range of values for relevant diagnostic features. Eye-tracking data
      indicated that there were four main regions of the pattern that analysts were
      most interested in. Within each region, individual elements or groups of elements
      that exhibited features associated with directionality, size, colour and shape
      appeared to capture the most interest of analysts during the classification task.
      The study showed that the eye movements of trained bloodstain pattern experts and
      their verbal descriptions of a pattern were well correlated.

PMID- 29046953
TI  - SNP typing using the HID-Ion AmpliSeqTM Identity Panel in a southern Chinese
      population.
AB  - In the present study, 90 autosomal single nucleotide polymorphisms (SNPs) and 34
      Y chromosomal SNPs were sequenced simultaneously using HID-Ion AmpliSeqTM
      Identity Panel on the Ion PGMTM platform for 125 samples in a southern Chinese
      population. Raw data were analyzed and forensic parameters were calculated.
      Haplogrouping concordance was also assessed using alternative methods based on Y
      SNP haplotypes and Y-STR haplotypes. The results showed that allelic imbalance
      occurred more frequently with low coverage while several SNPs with high coverage
      were also observed with poor allelic balance, including rs214955, rs430046,
      rs7520386, rs876724, rs9171188, rs16981290, and rs2032631. Totally, 21,261
      miscalled reads (0.28%) were observed. The rate of allele-specific miscalled
      reads (ASMRs) was higher than that of allele nonspecific miscalled reads (ANMRs)
      and associated with genetic diversity of the SNP. The ASMRs of major allele were
      lower than that of minor allele while there was no difference for ANMRs. The
      combined discrimination power (CDP) was 1-4.81 * 10-34 and the combined power of
      exclusion (CPE) was 0.99989 and 0.99999992 for duo and trio paternity testing,
      respectively. No significant genetic difference was detected between southern and
      northern Chinese populations. For haplogroup study, O2 was the predominant
      haplogroup and 97.01% of samples were assigned consistent haplogoups with Y-SNP
      and Y-STR haplotypes. In conclusion, the AmpliSeqTM Identity Panel was powerful
      for individual identification and trio paternity testing. ASMRs were associated
      with the genetic diversity and allele frequency while neither was related for
      ANMRs. High concordance of haplogrouping assignment can be obtained with Y-STR
      and Y-SNP haplotypes.

PMID- 29046955
TI  - The relationship between child and caregiver sleep in acute lymphoblastic
      leukemia maintenance.
AB  - PURPOSE: The purposes of this study are to describe sleep quality and sleep
      disturbance among caregivers of children in the maintenance phase of acute
      lymphoblastic leukemia (ALL) and to examine the relationship between sleep
      quality, child sleep disturbance, and caregiver guilt and worry. METHODS:
      Caregivers of 68 children with ALL, ages 3 to 12 years old, completed measures of
      caregiver guilt and worry, caregiver sleep quality, and child's developmental
      history and sleep habits. Demographic and treatment correlates of poor caregiver
      sleep were examined, and caregiver guilt and worry was tested as a moderator
      between child and caregiver sleep. RESULTS: More than half of caregivers (55.9%)
      reported clinically significant poor sleep and less than 40% were obtaining
      adequate sleep durations. Caregiver sleep was significantly related to child age
      at diagnosis, child sleep, and caregiver guilt and worry. Caregiver guilt and
      worry did not moderate the relationship between child sleep and caregiver sleep.
      CONCLUSIONS: Poor sleep is common in caregivers of children with cancer. Further
      research on the timing of sleep interventions and the most effective intervention
      targets are needed to maximize caregiver functioning during a child's cancer
      treatment. Targeted interventions seeking to improve caregiver sleep should be
      directed towards caregivers of children diagnosed in early childhood, caregivers
      of children with poor sleep, and caregivers with high guilt and worry.

PMID- 29046956
TI  - Unpredictable episodic breathlessness in patients with advanced chronic
      obstructive pulmonary disease and lung cancer: a qualitative study.
AB  - PURPOSE: The internationally consented definition and categorization describe two
      categories of episodic breathlessness: predictable (with known triggers) and
      unpredictable. The link of known triggers only to predictable episodes can be
      read that unpredictable episodes have none known trigger. Our aim was to
      illuminate patients' experiences with episodes of unpredictable breathlessness,
      to collect descriptions of the episodes' impact on the patients' lives, and, in
      turn, the patients' individual coping strategies in this connection. DESIGN:
      Qualitative study using semi-structured in-depth interviews with patients
      suffering from unpredictable episodes of breathlessness and chronic obstructive
      pulmonary disease (COPD; Global Initiative for Obstructive Lung Disease III and
      IV) or lung cancer (all stages). Interviews were audio-recorded, transcribed
      verbatim, and analyzed using Framework Analysis. RESULTS: One hundred one
      patients were screened in a large university hospital; ten participants fulfilled
      the inclusion criteria and provided consent. The experienced episodes were
      evaluated as unpleasant and with higher intensity compared to predictable
      episodes. Non-pharmacological interventions were identified as useful coping
      strategies. Interestingly, although patients experienced the episodes in an
      unpredictable manner, a trigger could be detected retrospectively for the
      majority of cases (mostly emotions (especially panic) and, occasionally, physical
      exertion). Unpredictable episodes are less frequent than previously assumed.
      CONCLUSION: The unpredictability of unpredictable breathless episodes refers to
      the patients' experience that these episodes occur "out-of-the-blue." However, a
      known trigger can be identified for the majority of unpredictable breathless
      episodes. These are therefore triggered as well. Further research needs to
      describe more possible triggers, to inquire the prevalence of unpredictable
      episodic breathlessness, and to develop effective management strategies.

PMID- 29046957
TI  - Heller myotomy versus Heller myotomy with Dor fundoplication for achalasia: long
      term symptomatic follow-up of a prospective randomized controlled trial.
AB  - BACKGROUND: Our prior randomized controlled trial of Heller myotomy alone versus
      Heller plus Dor fundoplication for achalasia from 2000 to 2004 demonstrated
      comparable postoperative resolution of dysphagia but less gastroesophageal reflux
      after Heller plus Dor. Patient-reported outcomes are needed to determine whether
      the findings are sustained long-term. METHODS: We actively engaged participants
      from the prior randomized cohort, making up to six contact attempts per person
      using telephone, mail, and electronic messaging. We collected patient-reported
      measures of dysphagia and gastroesophageal reflux using the Dysphagia Score and
      the Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL)
      instrument. Patient-reported re-interventions for dysphagia were verified by
      obtaining longitudinal medical records. RESULTS: Among living participants, 27/41
      (66%) were contacted and all completed the follow-up study at a mean of 11.8
      years postoperatively. Median Dysphagia Scores and GERD-HRQL scores were slightly
      worse for Heller than Heller plus Dor but were not statistically different (6 vs
      3, p = 0.08 for dysphagia, 15 vs 13, p = 0.25 for reflux). Five patients in the
      Heller group and 6 in Heller plus Dor underwent re-intervention for dysphagia
      with most occurring more than five years postoperatively. One patient in each
      group underwent redo Heller myotomy and subsequent esophagectomy. Nearly all
      patients (96%) would undergo operation again. CONCLUSIONS: Long-term patient
      reported outcomes after Heller alone and Heller plus Dor for achalasia are
      comparable, providing support for either procedure.

PMID- 29046958
TI  - Laparoscopic choledochoduodenostomy as a reliable rescue procedure for
      complicated bile duct stones.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with stone
      extraction is generally accepted as first line management for common bile duct
      (CBD) stones. CBD exploration, either by open or laparoscopic approach nowadays,
      is usually reserved for ERCP failures, complicated stone locations, along with
      altered anatomical situations. The aim of this study was to highlight the
      increasing role of laparoscopic choledochoduodenostomy which is not only a
      reliable but also as a rescue procedure for those failed ERCP cases due to
      complicated bile duct stones. MATERIALS AND METHODS: It is a retrospective review
      of the database, from a tertiary care teaching institution from India, from Jan
      2012 up to December 2016. RESULTS: Out of total 30 patients who underwent
      laparoscopic choledochoduodenostomy, 28 had failed ERC stone clearance while two
      patients were directly offered drainage in view of unfavorable anatomy. The major
      reasons for failed ERC stone clearance were as follows-multiple large calculi
      (42.8%), recurrent stones (21.4%), and associated stricture (21.4%). Mean
      operating time was 130 (+/- 27) minutes with mean blood loss of 60 (+/- 19) ml.
      Stone extraction was successful, primarily by milking in 13 (43.33%) patients,
      rest required augmentation by Dormia basket/balloon. Two patients (6.66%)
      developed controlled bile leak which resolved with conservative treatment. The
      median length of hospital stay was 5 days (IQR 3-9). Mean duration of follow-up
      was 17 (+/- 3.2) months. CONCLUSION: Laparoscopic common bile duct exploration
      with choledochoduodenostomy has been shown to be a safe, reliable, and efficient
      method for treating complex CBDS, especially after failed ERCP procedures.

PMID- 29046959
TI  - Minimally invasive liver resection for primary and metastatic liver tumors:
      influence of age on perioperative complications and mortality.
AB  - BACKGROUND: As minimally invasive technique becomes more popular, an increasing
      number of elderly patients were considered for minimally invasive liver resection
      (MILR). Limited physiologic reserve remains a major concern, which frequently
      leads surgeons to recommend nonresectional alternatives. We sought to evaluate
      complications and outcomes of elderly patients undergoing MILR. METHODS: Eight
      hundred and thirty-one patients who underwent MILR were classified into groups A,
      B, and C based on age [(< 70, n = 629), (70-79, n = 148), (>= 80, n = 54) years
      old, respectively]. RESULTS: Gender distribution, BMI, and cirrhotic status were
      comparable among all groups. Groups B and C had higher MELD (p = 0.047) and ASA
      (p = 0.001) scores. Operative time (170, 157, 152 min; p = 0.64) and estimated
      blood loss (145, 130, 145 ml; p = 0.95) were statistically equal. Overall
      postoperative complications were greater in groups B and C (12.9 and 9.3 vs.
      6.5%, respectively). Complications in group C were all minor. Clavien-Dindo grade
      III-IV complications were higher in group B when compared to group A (6.8 vs.
      2.7%, p = 0.43). There was no significant difference in cardiopulmonary
      complications, thromboembolic events, ICU admissions, and transfusion rates seen
      in groups B and C when compared to group A. Duration of hospital stay was
      statistically longer in groups B and C (3.6, 3.5 vs. 2.5 days, p = 0.0012). 30-
      and 90-day mortality rates were comparable among the groups, irrespective of age.
      CONCLUSIONS: In spite of greater preoperative comorbidities and ASA score, there
      was no significant increase in postoperative morbidity after minimally invasive
      liver resection in patients >= 70 years of age.

PMID- 29046960
TI  - Endoscopic submucosal dissection for undifferentiated-type early gastric cancer:
      short- and long-term outcomes.
AB  - BACKGROUND AND AIMS: Application of endoscopic submucosal dissection (ESD) for
      undifferentiated-type early gastric cancers (EGCs) remains controversial owing to
      limited data regarding long-term outcomes. We aimed to evaluate the feasibility
      of ESD for undifferentiated-type EGCs that meet the expanded criteria (EC).
      METHODS: We performed a retrospective analysis of 66 patients who underwent ESD
      for undifferentiated-type EGC between January 2005 and December 2014. We
      evaluated the rates of en bloc, complete, and curative resections along with
      overall survival (OS), disease-specific survival (DSS), and recurrence-free
      survival (RFS). RESULTS: Of the 66 patients, the EC group included 38 patients
      and the beyond-EC group included 28 patients. The overall rates of en bloc,
      complete, and curative resection of the 66 lesions were 92.4% (61/66), 65.2%
      (43/66), and 48.5% (32/66), respectively. Of the 34 patients with non-curative
      resection, 18 underwent additional surgery. Local remnant cancer was detected in
      1 patient (1/18, 5.6%), and none of the 18 patients had lymph node metastasis. On
      multivariate analysis, tumors > 2 cm [odd ratio (OR) 6.183, 95% confidence
      interval (CI) 1.279-29.880, p = 0.023) and submucosal invasion depth (OR 6.226,
      95% CI 1.881-20.606, p = 0.003) were independent predictors of incomplete
      resection. All 26 patients with more than 1 year of follow-up after curative
      resection survived without any evidence of local or distant recurrences over a
      median follow-up period of 36 months. The OS, DSS, and RFS rates of patients with
      curative ESD were 93.8, 100, and 100%, respectively. CONCLUSIONS: ESD may have
      favorable long-term outcomes in patients with undifferentiated-type EGC after
      curative resection.

PMID- 29046961
TI  - Modified peroral endoscopic myotomy: a "Push and Pull" technique.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) is a minimally invasive yet
      challenging procedure for achalasia. Additional technological innovations and
      improvements are important for simplifying the procedure. METHODS: We report the
      successful use of a modified POEM procedure, which utilized a "Push and Pull"
      technique, on a patient with achalasia. RESULTS: Our modifications resulted in a
      short operation time of only 35 min. No complications arose during or after the
      procedure, up to a follow-up period of 6 months, and symptoms were significantly
      and quickly improved. CONCLUSIONS: This modified procedure shortens operation
      time and lowers the difficulty of the operation, while leaving the safety and
      efficacy uncompromised.

PMID- 29046962
TI  - Comparison of posterior retroperitoneal and transabdominal lateral approaches in
      robotic adrenalectomy: an analysis of 200 cases.
AB  - BACKGROUND: Although numerous studies have been published on robotic
      adrenalectomy (RA) in the literature, none has done a comparison of posterior
      retroperitoneal (PR) and transabdominal lateral (TL) approaches. The aim of this
      study was to compare the outcomes of robotic PR and TL adrenalectomy. METHODS:
      This is a retrospective analysis of a prospectively maintained database. Between
      September 2008 and January 2017, perioperative outcomes of patients undergoing RA
      through PR and TL approaches were recorded into an IRB-approved database.
      Clinical and perioperative parameters were compared using Student's t test,
      Wilcoxon rank-sum test, and chi 2 test. Multivariate regression analysis was
      performed to determine factors associated with total operative time. RESULTS: 188
      patients underwent 200 RAs. 110 patients were operated through TL and 78 patients
      through PR approach. Overall, conversion rate to open was 2.5% and 90-day
      morbidity 4.8%. The perioperative outcomes of TL and PR approaches were similar
      regarding estimated blood loss, rate of conversion to open, length of hospital
      stay, and 90-day morbidity. PR approach resulted in a shorter mean +/- SD total
      operative time (136.3 +/- 38.7 vs. 154.6 +/- 48.4 min; p = 0.005) and lower
      visual analog scale pain score on postoperative day #1 (4.3 +/- 2.5 vs. 5.4 +/-
      2.4; p = 0.001). After excluding tumors larger than 6 cm operated through TL
      approach, the difference in operative times persisted (136.3 +/- 38.7 vs. 153.7
      +/- 45.7 min; p = 0.009). On multivariate regression analysis, increasing BMI and
      TL approaches were associated with longer total operative time. CONCLUSION: This
      study shows that robotic PR and TL approaches are equally safe and efficacious.
      With experience, shorter operative time and less postoperative pain can be
      achieved with PR technique. This supports the preferential utilization of PR
      approach in high-volume centers with enough experience.

PMID- 29046963
TI  - Cone beam computed tomography and ultrasonography imaging of benign intraosseous
      jaw lesion: a prospective radiopathological study.
AB  - OBJECTIVE: We assessed whether ultrasonography (US) can be used in combination
      with cone beam computed tomography (CBCT) to image intraosseous jaw lesions.
      MATERIAL AND METHODS: Using CBCT and US, we evaluated 123 lytic intraosseous jaw
      lesions diagnosed in 121 patients with guidance from the CBCT findings. The
      lesions were classified into two groups based on histopathological evaluation:
      (1) cysts and (2) tumors and tumor-like lesions. US and histopathological
      findings on the lesions of the two groups and their relationships with each other
      were also assessed. Results are reported as means +/- standard errors, and p <
      0.001 was accepted as indicating statistical significance. RESULT: In total, 123
      lesions were evaluated; 74 (60.2%) were cysts and 49 (39.8%) were tumors or tumor
      like lesions. The CBCT and US findings were compatible as far as dimensional
      measurements of the lesions in the three planes (p < 0.001). The US and
      histopathological findings on the content of the lesions correlated (p < 0.001).
      CONCLUSION: CBCT provides useful information for diagnosing intraosseous jaw
      lesions. Because it offers no valid Hounsfield unit (HU) value, it does not
      differentiate between solid and cystic masses. Thus, US can be used with CBCT to
      image intraosseous jaw lesions caused by buccal cortical thinning or perforation.
      CLINICAL RELEVANCE: US provides useful information about intraosseous jaw lesions
      and can be used with CBCT to image such lesions caused by buccal cortical
      thinning or perforation. Clinicians can take this information into consideration
      when evaluating intraosseous jaw pathology.

PMID- 29046964
TI  - Differences in maxillomandibular morphology among patients with
      mucopolysaccharidoses I, II, III, IV and VI: a retrospective MRI study.
AB  - OBJECTIVE: The aims of this study were to analyze the maxillomandibular
      morphology of patients with mucopolysaccharidosis (MPS) type I, II, III, IVa and
      VI and to evaluate the craniofacial effect of hematopoietic stem cell
      transplantation (HCST) in MPS I. MATERIALS AND METHODS: One hundred head magnetic
      resonance images were retrospectively analyzed from 41 MPS and 27 control
      individuals. The width, height and length of the maxilla and mandible were
      plotted against age and the means of controls, MPS I, MPS II and MPS III were
      statistically compared. To determine the effect of HSCT in MPS I, jaw morphology
      was compared between MPS I patients with full donor chimerism versus patients
      with mixed/no donor chimerism. RESULTS: Maxillary dimensions were not
      statistically different between the MPS types. The height and length of the
      mandible were clearly smaller in MPS I as compared to those in controls, MPS II
      and MPS III. This was associated with progressive resorption of the mandibular
      condyles in MPS I, which was also observed in MPS II and VI, but not in MPS III
      or IVa. Whereas the success of HCST did not affect these changes, mandibular
      width was significantly smaller in MPS I individuals with full donor chimerism.
      CONCLUSION: MPS I individuals have a smaller mandible as compared to control, MPS
      II and MPS III individuals due to progressive condylar degeneration. These
      abnormalities are also evident following successful HSCT. CLINICAL RELEVANCE:
      Clinicians should be aware of specific differences in mandibular morphology and
      condylar involvement among the MPS subtypes.

PMID- 29046965
TI  - Mother-infant bonding in the postpartum period: assessment of the impact of pre
      delivery factors in a clinical sample.
AB  - This study aims to examine the extent to which a variety of pre-delivery factors
      (demographic, reproductive, psychological, psychiatric, and psychopathological)
      predict disturbances in mother-infant bonding (MIB) in the postpartum period. Two
      hundred fifty-one pregnant women enrolled at a public perinatal psychiatric
      service were assessed between the first and second trimester of pregnancy and at
      6-7 weeks after delivery. During pregnancy, the psychological risk factors were
      assessed with the Vulnerable Personality Style Questionnaire, the Marital
      Adjustment Scale, the Early Trauma Inventory, and the General Health
      Questionnaire. To detect psychopathology, the Edinburgh Postnatal Depression
      Scale and the State-Trait Anxiety Inventory were used. At the postpartum
      evaluation, MIB was measured by the Postpartum Bonding Questionnaire. The results
      of the final regression model showed that emotional abuse in childhood, family
      psychiatric history, previous psychiatric hospitalization, and anxiety during
      pregnancy were significant predictors of MIB disturbances in postpartum,
      explaining 10.7% of the variance. The evaluation of women's risk factors in
      pregnancy is important in order to prevent MIB disturbances and thus to ensure
      the welfare of mothers and their babies.

PMID- 29046966
TI  - Substituent effects on the electronic structures and nonlinear optical properties
      of Li-doped nano-carbon bowl.
AB  - A series of Li-corannulene-(NH2)n and Li-corannulene-(NO2)n (n = 1, 2, 5)
      compounds have been theoretically designed and investigated using density
      functional theory. In this work, two models are systematically investigated to
      explore the important factors for enhancing the static first hyperpolarizability
      by introducing the substitution group. It is revealed that energy gaps (Egap)
      between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular
      orbital (LUMO) of all compounds are in the range of 4.149-4.934 eV. Different DFT
      methods are adopted to calculate polarizabilities and the first
      hyperpolarizabilities of Li-corannulene-(NH2)n and Li-corannulene-(NO2)n (n = 1,
      2, 5) compounds. It is revealed that polarizability values of the systems
      increase with increasing number of NH2/NO2 substitution group. Moreover, it is
      found that the first hyperpolarizabilities of Li-corannulene-(NO2)n are larger
      than those of Li-corannulene-(NH2)n, which can be attributed to the lower
      transition energies. In contrast to the NH2 substitution group, NO2 substitution
      group can be more powerful in increasing the first hyperpolarizability of Li
      doped corannulene. We hope that this study can provide a new idea for designing
      nonlinear optical materials using the NH2 and NO2 groups.

PMID- 29046967
TI  - What do docking and QSAR tell us about the design of HIV-1 reverse transcriptase
      nonnucleoside inhibitors?
AB  - Despite vigorous studies, effective nonnucleoside inhibitors of HIV-1 reverse
      transcriptase (NNRTIs) are still in demand, not only due to toxicity and
      detrimental side effects of currently used drugs but also because of the
      emergence of multidrug-resistant viral strains. In this contribution, we present
      results of docking of 47 inhibitors to 107 allosteric centers of HIV-1 reverse
      transcriptase. Based on the average binding scores, we have constructed QSAR
      equations to elucidate directions of further developments in the inhibitor design
      that come from this structural data.

PMID- 29046968
TI  - Development of an elution device for ViroCap virus filters.
AB  - Environmental surveillance of waterborne pathogens is vital for monitoring the
      spread of diseases, and electropositive filters are frequently used for sampling
      wastewater and wastewater-impacted surface water. Viruses adsorbed to
      electropositive filters require elution prior to detection or quantification.
      Elution is typically facilitated by a peristaltic pump, although this requires a
      significant startup cost and does not include biosafety or cross-contamination
      considerations. These factors may pose a barrier for low-resource laboratories
      that aim to conduct environmental surveillance of viruses. The objective of this
      study was to develop a biologically enclosed, manually powered, low-cost device
      for effectively eluting from electropositive ViroCapTM virus filters. The elution
      device described here utilizes a non-electric bilge pump, instead of an electric
      peristaltic pump or a positive pressure vessel. The elution device also fully
      encloses liquids and aerosols that could contain biological organisms, thereby
      increasing biosafety. Moreover, all elution device components that are used in
      the biosafety cabinet are autoclavable, reducing cross-contamination potential.
      This device reduces costs of materials while maintaining convenience in terms of
      size and weight. With this new device, there is little sample volume loss due to
      device inefficiency, similar virus yields were demonstrated during seeded studies
      with poliovirus type 1, and the time to elute filters is similar to that required
      with the peristaltic pump. The efforts described here resulted in a novel, low
      cost, manually powered elution device that can facilitate environmental
      surveillance of pathogens through effective virus recovery from ViroCap filters
      while maintaining the potential for adaptability to other cartridge filters.

PMID- 29046970
TI  - A focused evaluation of lumbar spine trabecular bone score in the first year post
      menarche.
AB  - : Trabecular bone score, an index of lumbar spine trabecular texture, has not
      been explored fully in adolescent girls. Our cross-sectional analysis supported
      the hypothesis that "adult normal" trabecular bone score has been achieved by the
      end of the first year post-menarche, providing a potential screening tool,
      independent from bone density. INTRODUCTION: Trabecular bone score (TBS)
      evaluates lumbar spine (LS) trabecular texture from DXA images. Limited evidence
      suggests low TBS in pre-pubertal girls. TBS has not been assessed in the context
      of the key peri-menarcheal bone accrual phase. Thus, we evaluated (1) whether
      "normal" adult TBS (>= 1.35) is reached in the first year post-menarche and (2)
      the role of maturational timing (menarcheal age) and status (gynecological age)
      in TBS variation. METHODS: For 44 healthy girls aged 11 to 13 years, whole body
      and LS DXA scans were obtained within 1 year post-menarche. As TBS is optimized
      for adults and can be affected by body thickness, custom software provided
      unadjusted "rawTBS" and adjusted for tissue thickness "corrTBS" (TBS iNsight,
      Medimaps, France). Correlations evaluated menarcheal age and gynecological age as
      factors in LS bone mineral content (BMC), areal bone mineral density (BMD), and
      TBS. RESULTS: Lowest observed TBS exceeded 1.35 (rawTBS = 1.362; corrTBS =
      1.352). Menarcheal age correlated negatively with rawTBS (r = - 0.34, p = 0.02),
      with a similar trend for corrTBS (r = - 0.29, p < 0.06). Gynecological age did
      not correlate with TBS but was positively correlated with LSBMD (r = + 0.37, p =
      0.01). Correlations with body composition variables differed between rawTBS and
      corrTBS. CONCLUSIONS: In this healthy cohort, "normal" adult TBS is present by 1
      year post-menarche, 2 years before projected LS peak bone mass. Thus, TBS may be
      a useful bone architectural screen during the first post-menarcheal year,
      enabling intervention to improve structure prior to "peak bone mass".
      Longitudinal studies are needed to elucidate TBS development and intervention
      response.

PMID- 29046969
TI  - Determination of airborne trace elements in an urban area using lichens as
      biomonitor.
AB  - The amounts of elements emitted from industrial, domestic, and vehicle sources in
      Duzce through the analyses of lichens, which are bioindicators of air pollution,
      were determined in this research. Concentrations of Al, Fe, Cr, Mn, Co, Ni, Cu,
      Zn, As, V, Cd, Hg, and Pb in the lichens that were collected from 40 different
      points were analyzed using an inductively coupled plasma (ICP-MS) device. The
      highest concentration values were detected for Fe and Al, while the lowest
      concentration values were detected for Cd and Hg. Distribution maps of elements
      were created using geographic information systems. The distribution maps showed
      how the concentrations of elements for Duzce have changed across the city.
      According to our results, the elements sourced from traffic and combustion, such
      as Cr, Co, Ni, Cu, As, and V, have the highest concentrations in the city center
      near the traffic.

PMID- 29046971
TI  - Training and Service Provision in Cardiovascular CT: International Challenges and
      Solutions.
AB  - PURPOSE OF REVIEW: This manuscript identifies international challenges in
      cardiovascular CT that may prevent it from becoming a mainstream cardiovascular
      investigation. It offers potential solutions and a vision to overcome these
      barriers. RECENT FINDINGS: The acceptance of cardiovascular CT as a mainstream
      investigation now mandates a root and branch review of how we deliver a
      technology that is no longer emerging but recommended for mainstream clinical
      practice. The main challenges include investment in equipment and personnel and a
      substantial uplift in educational and training opportunities available. This
      requires revision of existing structures for training and accreditation and a
      broadening of these opportunities to include radiographers/technologists. The
      evidence for cardiovascular CT is overwhelming; the same energy and investment
      witnessed in driving the evidence base for this technology is now required in
      education and training. Failure to do so risks undermining the academic
      investment made over the last decade.

PMID- 29046972
TI  - Quantitative assessment of Urmia Lake water using spaceborne multisensor data and
      3D modeling.
AB  - Preserving aquatic ecosystems and water resources management is crucial in arid
      and semi-arid regions for anthropogenic reasons and climate change. In recent
      decades, the water level of the largest lake in Iran, Urmia Lake, has decreased
      sharply, which has become a major environmental concern in Iran and the region.
      The efforts to revive the lake concerns the amount of water required for
      restoration. This study monitored and assessed Urmia Lake status over a period of
      30 years (1984 to 2014) using remotely sensed data. A novel method is proposed
      that generates a lakebed digital elevation model (LBDEM) for Urmia Lake based on
      time series images from Landsat satellites, water level field measurements,
      remote sensing techniques, GIS, and 3D modeling. The volume of water required to
      restore the Lake water level to that of previous years and the ecological water
      level was calculated based on LBDEM. The results indicate a marked change in the
      area and volume of the lake from its maximum water level in 1998 to its minimum
      level in 2014. During this period, 86% of the lake became a salt desert and the
      volume of the lake water in 2013 was just 0.83% of the 1998 volume. The volume of
      water required to restore Urmia Lake from benchmark status (in 2014) to
      ecological water level (1274.10 m) is 12.546 Bm3, excluding evaporation. The
      results and the proposed method can be used by national and international
      environmental organizations to monitor and assess the status of Urmia Lake and
      support them in decision-making.

PMID- 29046973
TI  - Clinical Management of Cavernous Malformations.
AB  - PURPOSE OF REVIEW: This study aims to review the current epidemiology and
      clinical management of patients with cavernous malformations (CM). RECENT
      FINDINGS: Hemorrhage is the most feared complication and leads to morbidity in
      patients with CM. Multiple studies including three meta-analyses have provided
      useful estimates of hemorrhage risk, but have failed to identify a modifiable
      risk factor for prevention of cavernous malformation related hemorrhage. In
      treating the CM itself, surgical risk is weighed against the natural history.
      However, accumulating knowledge regarding the roles of CCM 1, 2, and 3 genes has
      led to the discovery of potential therapeutic targets. The risk of future
      hemorrhage in patients with CM is highest in those who have had previously
      clinical hemorrhages. Estimated risks are helpful in counseling patients and
      comparing to the risk of surgery. Future clinical trials of candidate medications
      are likely to target those patients with prior clinical hemorrhage in whom the
      surgical risk is deemed high.

PMID- 29046974
TI  - Stress Echocardiography in Stable Coronary Artery Disease.
AB  - PURPOSE OF REVIEW: Stress echocardiography (SE) is a well-established technique
      for the diagnosis and risk stratification of patients with known or suspected
      coronary artery disease (CAD). This review article summarizes the status of SE in
      CAD, including testing protocols, clinical efficacy and current use of newer
      technologies: myocardial perfusion, strain imaging, three-dimensional
      echocardiography and adjunctive carotid ultrasonography. RECENT FINDINGS: Recent
      major findings in SE include the clinical value of myocardial perfusion imaging
      in multicentre studies, as well as when added to left ventricular (LV) wall
      motion assessment in clinical service. Additionally, SE has been shown to be more
      cost-effective than exercise ECG in patients with low-intermediate pre-test
      probability of CAD. Adjunctive atherosclerosis imaging by carotid ultrasonography
      (CU) to ischaemia testing by SE provides synergistic prognostic value, equivalent
      to hybrid imaging by PET-CT. Despite the development of newer and more expensive
      imaging modalities, SE remains the cornerstone for the assessment of CAD and has
      excellent clinical efficacy, is safe and is cost-effective.

PMID- 29046975
TI  - The Genetics of Physical Activity.
AB  - PURPOSE OF REVIEW: Physical activity (PA) is a well-established modifiable
      lifestyle determinant for multiple cardio-metabolic outcomes. While many
      psychosocial and environmental correlates of PA have been identified, current
      understanding of the genetic architecture that contributes to PA is still very
      limited, especially when compared to other phenotypes such as obesity and
      diabetes. RECENT FINDINGS: This review systematically and comprehensively
      assesses available evidence from animal experiments, family studies, population
      based candidate gene analyses, and genome-wide association studies (GWAS)
      studying the genetics of physical activity patterns. It discusses the scientific
      evolution in the field of PA genetics, including the recognition of increased
      sample sizes, the shift from early family-based approaches to association-based
      design, and the rapidly advancement of enabling genotyping and sequencing
      technologies. In addition, this review points to the gaps in the current
      knowledge base, including the general lack of GWAS and whole-genome sequence
      analyses particularly understudied populations, and the need for large-scale
      collaborative effort in both observational and experimental settings. In this
      review, we also call for research utilizing systems biology strategies for PA
      genetic research and accounting for complex gene-environment interactions that
      may vary by race/ethnicity. The epidemic of physical inactivity has been a public
      health nemesis, encompassing a large burden of diseases and high societal costs.
      A better understanding of the genetic basis of PA can inform public health
      policies for the prevention, control, and treatment of many chronic diseases
      related to physical inactivity.

PMID- 29046977
TI  - Carotid Angioplasty and Stenting and Embolic Protection.
AB  - PURPOSE OF REVIEW: We review the evidence on the safety and efficacy of carotid
      angioplasty and stenting (CAS) compared to carotid endarterectomy (CEA) and also
      summarizes emerging technical issues. RECENT FINDINGS: Randomized trials have
      demonstrated a progressive decrease of periprocedural strokes after CAS. Overall,
      in symptomatic patients, CAS is associated with a slightly higher risk of
      periprocedural strokes when compared to CEA. This is especially true after the
      age of 70 and immediately after a presenting symptomatic event. CAS is associated
      with lower incidence of periprocedural cardiac events and cranial nerve palsies.
      Both procedures are equally effective in preventing future ipsilateral ischemic
      events, and restenosis after CAS is not a major limitation. In asymptomatic
      patients, CAS is as safe as CEA, although modern medical therapy may be as
      effective as any carotid intervention. CAS is a valid alternative to CEA in
      selected patients with symptomatic carotid stenosis. In asymptomatic patients,
      the two procedures are equally safe, although medical therapy alone may be as
      effective.

PMID- 29046976
TI  - The Complement System and Preeclampsia.
AB  - PURPOSE OF REVIEW: Preeclampsia affects 3-4% of pregnancies with few treatment
      options to reduce maternal and fetal harm. Recent evidence that targeting the
      complement system may be an effective therapeutic strategy in prevention or
      treatment of preeclampsia will be reviewed. RECENT FINDINGS: Studies in humans
      confirm the safety and efficacy of C5 blockade in complement-mediated disorders
      of pregnancy, including preeclampsia. Animal models mimic the placental
      abnormalities and/or the maternal symptoms which characterize preeclampsia. These
      models in mouse and rat have defined a role for complement and its regulators in
      placental dysfunction, hypertension, proteinuria, endothelial dysfunction, fetal
      growth restriction, and angiogenic imbalance, thus informing future human
      studies. Targeting excessive complement activation, particularly the terminal
      complement complex (C5b-9) and C5a may be an effective strategy to prolong
      pregnancy in women with preeclampsia. Continued research is needed to identify
      the initiator(s) of activation, the pathways involved, and the key component(s)
      in the pathophysiology to allow development of safe and effective therapeutics to
      target complement without compromising its role in homeostasis and host defense.

PMID- 29046978
TI  - Blood Pressure Response to Exercise and Cardiovascular Disease.
AB  - PURPOSE OF REVIEW: This review aimed to provide a clinical update on exercise
      blood pressure (BP) and its relationship to cardiovascular disease (CVD),
      outlining key determinants of abnormal exercise BP responses. We also highlight
      current evidence gaps that need addressing in order to optimise the relevance of
      exercise BP as clinical CVD risk factor. RECENT FINDINGS: Abnormal exercise BP
      manifests as either exercise hypotension (low BP response) or as exaggerated
      exercise BP (high BP response). Exercise hypotension is an established sign of
      existing and likely severe CVD, but exaggerated exercise BP also carries elevated
      CVD risk due to its association with sub-clinical hypertension. Although
      exaggerated exercise BP is related to heightened CVD risk at any exercise
      intensity, recent data suggest that the BP response to submaximal intensity
      exercise holds greater prognostic and clinical significance than BP achieved at
      peak/maximal intensity exercise. Cardiorespiratory fitness is a strong modifier
      of the exercise BP response, and should be taken into consideration when
      assessing the association with CVD. Both exercise hypotension and exaggerated
      exercise BP serve as markers that should prompt evaluation for potential
      underlying CVD. However, the clinical utility of these markers is currently
      inhibited by the lack of consensus informing the definitions and thresholds for
      abnormalities in exercise BP.

PMID- 29046980
TI  - Aortic Stiffness in Aging and Hypertension: Prevention and Treatment with
      Habitual Aerobic Exercise.
AB  - PURPOSE OF REVIEW: Habitual aerobic exercise is associated with lower aortic
      stiffness, as measured by carotid-femoral pulse wave velocity (CFPWV), in middle
      aged/older adults without hypertension, but beneficial effects of aerobic
      exercise on CFPWV in hypertension remain contraversial. Therefore, the focus of
      this review is to discuss the evidence for and against the beneficial effects of
      aerobic exercise on aortic stiffness in middle-aged and older adults with
      hypertension, possible limitations in these studies, and highlight novel
      directions for future research. RECENT FINDINGS: Most randomized controlled
      intervention studies demonstrate that short-term aerobic exercise results in no
      reductions in CFPWV in middle-aged and/or older adults with treated or treatment
      naive hypertension. Higher aerobic fitness is not associated with lower aortic
      stiffness among older adults with treated hypertension. Aortic stiffness appears
      to be resistant to clinically relevant improvements in response to habitual
      aerobic exercise in the presence of hypertension among middle-aged and older
      adults.

PMID- 29046979
TI  - Medical Management of Pulmonary Hypertension with Unclear and/or Multifactorial
      Mechanisms (Group 5): Is There a Role for Pulmonary Arterial Hypertension
      Medications?
AB  - PURPOSE OF REVIEW: The purpose of this review was to outline the mechanisms and
      to review recent literature on pulmonary arterial hypertension (PAH) medications
      in group 5 pulmonary hypertension (PH). RECENT FINDINGS: The first steps in
      management are to understand the mechanisms and hemodynamic profile and to
      exclude chronic thromboembolic disease. Recent studies in the past 5 years have
      found that PAH medications may improve hemodynamics in patients with pre
      capillary pulmonary hypertension due to sarcoidosis, pulmonary Langerhans cell
      histiocytosis, lymphangioleiomyomatosis, and myeloproliferative disorders with
      dasatinib-induced PH. Improvements in exercise capacity are uncommon, and no
      survival benefit has been demonstrated. There is a risk of pulmonary edema in
      patients with pulmonary venous involvement or fibrosing mediastinitis when
      treated with PAH therapies. There is limited evidence supporting the use of PAH
      medications in group 5 patients, and they may be harmful in certain cases. In
      most patients with group 5 PH, treatment should be directed to the underlying
      disease with PAH therapies reserved for patients with severe pre-capillary PH.

PMID- 29046981
TI  - Ophthalmologic Disease in HIV Infection: Recent Changes in Pathophysiology and
      Treatment.
AB  - PURPOSE OF REVIEW: Ophthalmologic conditions were among the earliest described
      findings in patients with the acquired immunodeficiency syndrome (AIDS). The
      purpose of this review is to highlight recent changes in the pathophysiology and
      management of ophthalmologic conditions in patients infected with the human
      immunodeficiency virus (HIV). RECENT FINDINGS: The introduction of highly active
      antiretroviral therapy (HAART) in 1996 changed ophthalmologic findings from
      predominantly acute infectious diseases to chronic, slowly progressive,
      debilitating conditions. HIV-associated neuroretinal disorder infrequently leads
      to blindness, but it causes visual disability in a large percentage of patients.
      Cytomegalovirus retinitis is now seen less commonly in the USA, but it remains an
      important cause of blindness in HIV-infected patients from developing countries.
      Immune recovery uveitis has emerged as a major cause of visual disability in the
      USA. As HIV has become a chronic disease, visual disability due to chronic
      noninfectious diseases have become increasingly important.

PMID- 29046982
TI  - Ureteroscopy for Stone Disease in Paediatric Population is Safe and Effective in
      Medium-Volume and High-Volume Centres: Evidence from a Systematic Review.
AB  - PURPOSE OF REVIEW: The incidence of urinary stone disease among the paediatric
      population is increasing. Whilst there has been a rise in the number of original
      studies published on ureteroscopy (URS) in children, critical review still
      remains under-reported. RECENT FINDINGS: A Cochrane style systematic review was
      performed to identify all original articles on URS (minimum of 25 cases) for
      stone disease in paediatric patients between Jan. 1996 and Dec. 2016. Based on
      the number of reported cases, centres were divided into medium (25-49 cases) and
      high (>= 50 cases) volume studies. Thirty-four studies (2758 children) satisfied
      our search criteria and were included in this review. The mean stone size was 8.6
      mm with an overall stone-free rate (SFR) of 90.4% (range 58-100). Medium-volume
      centres reported a mean SFR of 94.1% (range 87.5-100), whilst high-volume centres
      reported a mean SFR of 88.1% (range 58-98.5). Mean number of sessions to achieve
      stone-free status in medium-volume and high-volume groups was 1.1 and 1.2
      procedures/patient respectively. The overall complication rate was 11.1%
      (327/2994). Breakdown by Clavien grade was as follows: Clavien I 69% and Clavien
      II/III 31%. There were no Clavien IV/V complications, and no mortality was
      recorded across any of the studies. The overall failure to access rate was 2.5%
      (76/2944). Medium-volume and high-volume studies had overall complication rates
      of 6.9% (37/530) and 12.1% (287/2222) respectively, but there was no significant
      difference in major or minor complications between these two groups. Ureteroscopy
      is a safe and effective treatment for paediatric stone disease. Medium-volume
      centres can achieve equally high SFRs and safety profiles as high-volume centres.
      Despite the rarity of paediatric stone disease, our findings might increase the
      uptake of paediatric URS procedures.

PMID- 29046983
TI  - Holmium Laser Enucleation of the Prostate: Patient Selection and Outcomes.
AB  - PURPOSE OF REVIEW: Holmium laser enucleation of the prostate (HoLEP) is a proven
      technique to alleviate bladder outlet obstruction (BOO) from benign prostatic
      hyperplasia (BPH). Herein, we review factors relevant to selecting patients who
      will benefit from this procedure and expected outcomes. RECENT FINDINGS: New
      randomized trials have validated the excellent outcomes achieved by HoLEP in the
      management of BOO from BPH. Its success has been reproduced in a diverse array of
      patients including those on anticoagulation, with detrusor
      underactivity/acontractility, prostate cancer, and in the retreatment setting.
      HoLEP can be applied to the majority of patients with BOO from BPH regardless of
      prostate size, previous operations, or the condition of the detrusor. HoLEP can
      also be carefully considered in patients requiring anticoagulation or who are
      undergoing active surveillance for low-risk prostate cancer. Immediate
      complication rate is low and incontinence is rare. Retrograde ejaculation occurs
      in approximately 75% patients. Furthermore, the retreatment rate for HoLEP is
      lower than reported for other endoscopic BPH procedures demonstrating its
      durability.

PMID- 29046984
TI  - Spatial Tracking of Targeted Prostate Biopsy Locations: Moving Towards Effective
      Focal Partial Prostate Gland Ablation with Improved Treatment Planning.
AB  - The ability to selectively characterize, localize, and predict the specific areas
      of the prostate gland which harbor the worst biologic behavior is requisite for
      optimal prostate cancer therapy, especially in the emerging field of partial
      prostate gland ablation (focal therapy). In this manuscript, we highlight
      contemporary techniques in target tracking for focal therapy planning.
      Multiparametric magnetic resonance imaging has emerged as a dominant strategy to
      localize biopsy sites most likely to contain high-grade lesions. In-bore MRI
      biopsy and MR/US fusion biopsy using cognitive or software-enhanced co
      registration have also become the most common strategy to accomplish this
      technical challenge. Such advances have led to growing optimism in the field of
      focal therapy for prostate cancer.

PMID- 29046985
TI  - New Devices and Technologies for the Management of Overactive Bladder.
AB  - PURPOSE OF REVIEW: Overactive bladder (OAB) affects millions of people in the USA
      and has a significant impact on their quality of life. Despite having a number of
      safe and effective ways of managing refractory OAB patients, there are many
      promising new technologies actively being studied and developed for the treatment
      of this population. This review examines current new devices and technologies
      under study for the treatment of OAB. RECENT FINDINGS: Modifications to already
      established therapies such as sacral nerve stimulation (SNS) or tibial nerve
      stimulation (TNS) are currently being studied for refractory OAB. On the SNS
      front, a newly rechargeable, smaller neurostimulator has been developed and has
      shown promising results for the treatment of refractory OAB. There are two newly
      implantable TNS devices actively being studied for the treatment of refractory
      OAB. These implanted TNS systems will allow the patient to receive treatment from
      the comfort of their home without the need for frequent office visits. Most
      recently, radiofrequency ablation intravesical therapy has been proposed as a
      newer technology with the potential to reduce OAB symptoms. There are many new
      technologies actively being studied and developed for the management of
      refractory OAB patients. If shown to be safe and efficacious, these therapies may
      one day alter our current management of patients with OAB.

PMID- 29046987
TI  - Blood Pressure Parameters and their Associations with Death in Patients with
      Chronic Kidney Disease.
AB  - PURPOSE OF REVIEW: Optimal blood pressure (BP) parameters among patients with
      chronic kidney disease (CKD) have been a matter of debate. This review critically
      evaluates recent literature to better define the associations of BP parameters
      and death among individuals with non-dialysis-dependent CKD. RECENT FINDINGS:
      Observational studies report a "U- or J-shaped" association between BP and all
      cause mortality in CKD and caution-intensive BP lowering in the elderly. Causes
      of death have been evaluated in a recent report noting higher cardiovascular and
      non-cardiovascular/non-malignant-related mortality among CKD population with SBP
      < 110 and > 150 mmHg. Very few randomized control trials evaluated the impact of
      different BP targets on patient-centered outcomes in those with CKD. Recently
      published SPRINT trial results suggest that intensive SBP control (<120 mm Hg)
      reduces cardiovascular events and all-cause death among non-diabetic patients
      with and without CKD. Clinical trial evidence supports lower BP target in those
      with mild to moderate non-diabetic CKD. However, clinical trials are warranted to
      further determine the beneficial effects of intensive blood pressure control in
      diabetic CKD population. In elderly population with CKD, BP targets might need to
      be individualized based on their comorbidities, life expectancy, and other
      factors.

PMID- 29046986
TI  - Predictability and Practicality of Image-Based Scoring Systems for Patient
      Assessment and Outcome Stratification During Percutaneous Nephrolithotomy: a
      Contemporary Update.
AB  - Preoperative nomograms offer systematic and quantitative methods to assess
      patient- and stone-related characteristics and their impact on successful
      treatment and potential risk of complication. Discrepancies in the correlation of
      perioperative variables to patient outcomes have led to the individual
      development, validation, and application of four independent scoring systems for
      the percutaneous nephrolithotomy: Guy's stone score, S.T.O.N.E. nephrolithometry,
      Clinical Research Office of the Endourology Society nomogram, and Seoul National
      University Renal Stone Complexity. The optimal nomogram should have high
      predictive ability, be practically integrated into clinical use, and be widely
      applicable to urinary stone disease. Herein, we seek to provide a contemporary
      evaluation of the advantages, disadvantages, and commonalities of each scoring
      system. While the current data is insufficient to conclude which scoring system
      is destined to become the gold standard, it is crucial that a nephrolithometric
      scoring system be incorporated into common practice to improve surgical planning,
      patient counseling, and outcome assessment.

PMID- 29046988
TI  - Should Pre-hypertension Be Treated?
AB  - Hypertension is an important preventable risk factor for disease and death
      worldwide. In light of the world's population growth and aging, hypertension is a
      global public health issue. Many studies have shown associations between pre
      hypertension and a higher risk of the future development of hypertension and
      cardiovascular disease in general populations. However, pre-hypertension per se
      is not a disease with an immediate high risk, and the clinical value of the
      identification of pre-hypertension is the potential detection of the early stage
      of the risk of hypertension and/or cardiovascular disease over an individual's
      lifespan. We recently assessed the impacts of age-related differences in risk
      factors on new-onset hypertension among normotensive individuals. As risk factors
      of the new onset of hypertension, the impact of diastolic blood pressure compared
      with systolic blood pressure (SBP), men compared with women, and higher body mass
      index were greater in the younger adults, whereas in the older adults, the impact
      of SBP and female sex were greater. Proteinuria was a risk factor for
      hypertension in both younger and older adults. Non-pharmacological approaches
      such as body weight reduction, low-salt diet, physical exercise, and good sleep
      hygiene should be first-line treatments for pre-hypertension. In addition,
      careful observation to detect the new onset of hypertension and the
      identification of the appropriate timing of pharmacologic treatment should be
      conducted, especially in adults with pre-hypertension and the risk factors
      mentioned above.

PMID- 29046989
TI  - Epilepsy and Psychiatric Comorbidities: Drug Selection.
AB  - Purpose of review The pharmacological treatment of patients with epilepsy and
      psychiatric comorbidities may sometimes represent a therapeutic challenge. This
      review is focused on the pharmacological management of patients with epilepsy and
      psychiatric problems in terms of rationalization of the antiepileptic drug (AED)
      treatment and the pharmacological management of the most clinically relevant
      psychiatric comorbidities, namely mood and anxiety disorders, psychoses, and
      attention deficit hyperactivity disorder (ADHD). Recent findings Up to 8% of
      patients with drug-resistant epilepsy develop treatment-emergent psychiatric
      adverse events of AED regardless of the mechanism of action of the drug and this
      is usually related to an underlying predisposition given by the previous
      psychiatric history and the involvement of mesolimbic structures. Careful history
      taking, periodic screening for mood and anxiety disorders, low starting doses,
      and slow titration schedules can reduce the possibility of AED-related problems.
      A pragmatic checklist for the pharmacological management of patients with
      epilepsy and psychiatric disorders is presented. Summary patients should be
      informed of potential behavioral effects of AEDs but no drugs should be excluded
      a priori. Any psychiatric comorbidity should be addressed in the appropriate
      setting and full remission and recovery should always represent the first goal of
      any therapeutic intervention. Neurologists should be aware of the side effects of
      major psychotropic drug classes in order to fully counsel their patients and
      other health professionals involved.

PMID- 29046990
TI  - Active force maintains the stability of a contractile ring.
AB  - We investigate a system of sufficiently dense polar actin filaments considered
      rigid and cross-linked by dimer myosin II protein within the contractile ring.
      The Langevin dynamics of this system is cast in a functional integral formalism
      and then transformed into density variables. Using the dynamical Random Phase
      Approximation (RPA) along with the a one-dimensional Langevin dynamics simulation
      (LDS), we investigate the structural integrity of the actin bundle network. The
      active force and the networking force reveal a non-trivial diffusive behaviour of
      the filaments within the ring. We conclude on when the active and networking
      forces lead to the contractile ring breaking down. The non-equilibrium active
      force is predominantly responsible for the prevention of the gaps in the ring.

PMID- 29046991
TI  - Implications of allometric model selection for county-level biomass mapping.
AB  - BACKGROUND: Carbon accounting in forests remains a large area of uncertainty in
      the global carbon cycle. Forest aboveground biomass is therefore an attribute of
      great interest for the forest management community, but the accuracy of
      aboveground biomass maps depends on the accuracy of the underlying field
      estimates used to calibrate models. These field estimates depend on the
      application of allometric models, which often have unknown and unreported
      uncertainties outside of the size class or environment in which they were
      developed. RESULTS: Here, we test three popular allometric approaches to field
      biomass estimation, and explore the implications of allometric model selection
      for county-level biomass mapping in Sonoma County, California. We test three
      allometric models: Jenkins et al. (For Sci 49(1): 12-35, 2003), Chojnacky et al.
      (Forestry 87(1): 129-151, 2014) and the US Forest Service's Component Ratio
      Method (CRM). We found that Jenkins and Chojnacky models perform comparably, but
      that at both a field plot level and a total county level there was a ~ 20%
      difference between these estimates and the CRM estimates. Further, we show that
      discrepancies are greater in high biomass areas with high canopy covers and
      relatively moderate heights (25-45 m). The CRM models, although on average ~ 20%
      lower than Jenkins and Chojnacky, produce higher estimates in the tallest forests
      samples (> 60 m), while Jenkins generally produces higher estimates of biomass in
      forests < 50 m tall. Discrepancies do not continually increase with increasing
      forest height, suggesting that inclusion of height in allometric models is not
      primarily driving discrepancies. Models developed using all three allometric
      models underestimate high biomass and overestimate low biomass, as expected with
      random forest biomass modeling. However, these deviations were generally larger
      using the Jenkins and Chojnacky allometries, suggesting that the CRM approach may
      be more appropriate for biomass mapping with lidar. CONCLUSIONS: These results
      confirm that allometric model selection considerably impacts biomass maps and
      estimates, and that allometric model errors remain poorly understood. Our
      findings that allometric model discrepancies are not explained by lidar heights
      suggests that allometric model form does not drive these discrepancies. A better
      understanding of the sources of allometric model errors, particularly in high
      biomass systems, is essential for improved forest biomass mapping.

PMID- 29046992
TI  - Managing Hypertension in Patients Aged 75 Years and Older.
AB  - On the basis of the available data, we would diagnose a normal blood pressure in
      elderly persons including those 75 years of age and older if the blood pressure
      was below 120/80 mmHg. We would diagnose hypertension in elderly persons
      including those aged 75 years and older if the systolic blood pressure was 130
      mmHg and higher or if the diastolic blood pressure was 80 mmHg and higher. We
      would treat these elderly patients with hypertension to a blood pressure goal of
      less than 130/80 mmHg if the blood pressure was obtained by automated blood
      pressure monitoring in a quiet room. We would consider treating high-risk persons
      aged 75 years and older to a blood pressure goal of less than 120/80 mmHg if they
      were carefully monitored for serious adverse events. If the blood pressure is
      more than 20/10 mmHg above the goal blood pressure, we would initiate
      antihypertensive drug therapy with two antihypertensive drugs. The initial drug
      of choice for the treatment of hypertension in adults aged 75 years and older
      should be based on co-morbidities, co-incidental indications, tolerability, and
      cost.

PMID- 29046993
TI  - Synthesis and In Vitro Performance of Polypyrrole-Coated Iron-Platinum
      Nanoparticles for Photothermal Therapy and Photoacoustic Imaging.
AB  - Multifunctional nano-platform for the combination of photo-based therapy and
      photoacoustic imaging (PAI) for cancer treatment has recently attracted much
      attention to nanotechnology development. In this study, we developed iron
      platinum nanoparticles (FePt NPs) with the polypyrrole (PPy) coating as novel
      agents for combined photothermal therapy (PTT) and PAI. The obtained PPy-coated
      FePt NPs (FePt@PPy NPs) showed excellent biocompatibility, photothermal
      stability, and high near-infrared (NIR) absorbance for the combination of PTT and
      PAI. In vitro investigation experimentally demonstrated the effectiveness of
      FePt@PPy NPs in killing cancer cells with NIR laser irradiation. Moreover, the
      phantom test of PAI used in conjunction with FePt@PPy NPs showed a strong
      photoacoustic signal. Thus, the novel FePt@PPy NPs could be considered as
      promising multifunctional nanoparticles for further applications of photo-based
      diagnosis and treatment.

PMID- 29046994
TI  - Peripheral markers of autophagy in polyglutamine diseases.
AB  - Polyglutamine disorders are neurodegenerative diseases that share a CAG repeat
      expansion in the coding region, resulting in aggregated proteins that can be only
      degraded through aggrephagy. We measured the expression of autophagy genes in
      peripheral blood mononuclear cells of 20 patients with Huntington's disease (HD),
      20 with spinocerebellar ataxia type 2 (SCA2), and 20 healthy individuals. HD
      patients showed increased expression of MAP1LC3B (+ 43%; p = 0.048), SQSTM1 (+
      49%; p = 0.002), and WDFY3 (+ 89%; p < 0.001). SCA2 patients had increased
      expression of WDFY3 (+ 69%; p < 0.001). We show that peripheral markers of
      autophagy are elevated in polyQ diseases, and this is particularly evident in HD.

PMID- 29046996
TI  - Predicting complexity of tumor removal and postoperative outcome in patients with
      high-grade gliomas.

PMID- 29046995
TI  - Aquablation of the Prostate for Symptomatic Benign Prostatic Hyperplasia: Early
      Results.
AB  - Aquablation is a novel technique for the surgical management of bladder outlet
      obstruction secondary to benign prostatic hyperplasia. Following first-in-man
      studies, a multicenter trial was conducted with results now out to 1 year.
      Aquablation resulted in a mean International Prostate Symptom Score improvement
      of 16 points (p < 0.01) and a mean maximum urinary flow rate increase from 8.7 to
      18.3 ml/s (p < 0.01) at 12 months. Due to the precise prostate mapping,
      aquablation has also demonstrated favorable sexual and urinary outcomes with no
      new erectile dysfunction, retrograde ejaculation, or urinary incontinence as
      often experienced with other techniques. These improvements in functional
      outcomes at 12 months confirm that aquablation is a safe and effective
      alternative for BPH treatment.

PMID- 29046997
TI  - Membrane perturbation through novel cell-penetrating peptides influences
      intracellular accumulation of imatinib mesylate in CML cells.
AB  - Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia
      chromosome generated through reciprocal translocation of chromosome 9 and 22. The
      use of first- and second-generation tyrosine kinase inhibitors has been
      successful to an extent. However, resistance against such drugs is an emerging
      problem. Apart from several drug-resistant mechanisms, drug influx/efflux ratio
      appears to be one of the key determinants of therapeutic outcomes. In addition,
      intracellular accumulation of drug critically depends on cell membrane fluidity
      and lipid raft dynamics. Previously, we reported two novel cell-penetrating
      peptides (CPPs), namely, cationic IR15 and anionic SR11 present in tryptic digest
      of Abrus agglutinin. Here, the potential of IR15 and SR11 to influence
      intracellular concentration of imatinib has been evaluated. Fluorescent
      correlation spectroscopy and lifetime imaging were employed to map membrane
      fluidity and lipid raft distribution following peptide-drug co-administration.
      Results show that IR15 and SR11 are the two CPPs which can modulate membrane
      fluidity and lipid raft distribution in K562 cells. Both IR15 and SR11
      significantly reduce the viability of CML cells in the presence of imatinib by
      increasing the intracellular accumulation of the drug.

PMID- 29046998
TI  - Metabolite profiling and associated gene expression reveal two metabolic shifts
      during the seed-to-seedling transition in Arabidopsis thaliana.
AB  - KEY MESSAGE: Metabolic and transcriptomic correlation analysis identified two
      distinctive profiles involved in the metabolic preparation for seed germination
      and seedling establishment, respectively. Transcripts were identified that may
      control metabolic fluxes. The transition from a quiescent metabolic state (dry
      seed) to the active state of a vigorous seedling is crucial in the plant's life
      cycle. We analysed this complex physiological trait by measuring the changes in
      primary metabolism that occur during the transition in order to determine which
      metabolic networks are operational. The transition involves several developmental
      stages from seed germination to seedling establishment, i.e. between imbibition
      of the mature dry seed and opening of the cotyledons, the final stage of seedling
      establishment. We hypothesized that the advancement of growth is associated with
      certain signature metabolite profiles. Metabolite-metabolite correlation analysis
      underlined two specific profiles which appear to be involved in the metabolic
      preparation for seed germination and efficient seedling establishment,
      respectively. Metabolite profiles were also compared to transcript profiles and
      although transcriptional changes did not always equate to a proportional
      metabolic response, in depth correlation analysis identified several transcripts
      that may directly influence the flux through metabolic pathways during the seed
      to-seedling transition. This correlation analysis also pinpointed metabolic
      pathways which are significant for the seed-to-seedling transition, and
      metabolite contents that appeared to be controlled directly by transcript
      abundance. This global view of the transcriptional and metabolic changes during
      the seed-to-seedling transition in Arabidopsis opens up new perspectives for
      understanding the complex regulatory mechanism underlying this transition.

PMID- 29046999
TI  - Attentional Orienting to Emotional Faces Moderates the Association Between
      Callous-Unemotional Traits and Peer-Nominated Aggression in Young Adolescent
      School Children.
AB  - Callous-unemotional (CU) traits are associated with aggressive behavior but
      preliminary research suggests this relationship is modified by patterns of
      emotional processing. This study examined whether attentional orienting to
      emotional faces moderated the association between CU traits and peer-nominated
      aggression in 251 middle school students (53% females, mean age = 13.24 years, SD
      = 0.73). Attentional orienting was assessed using an emotional faces (i.e.,
      angry, fearful, happy, sad, and neutral) variant of the dot-probe task. Students
      also completed a self-report measure of CU traits and their classmates made peer
      nominations of aggression. Logistic regression analyses showed that peer
      nominated aggression was positively related to CU traits at low levels of
      attentional orienting to angry faces, whereas aggression was unrelated to CU
      traits at high levels of attentional orienting to angry faces. That is, peer
      nominated aggression was greatest for youth high on CU traits who were not
      engaged by angry faces. These findings support the importance of considering
      different patterns of emotional responding when studying the association between
      CU traits and aggressive behavior in youth.

PMID- 29047000
TI  - Latent Class Analysis of HIV Risk Behaviors Among Russian Women at Risk for
      Alcohol-Exposed Pregnancies.
AB  - The number of HIV cases attributed to heterosexual contact and the proportion of
      women among HIV positive individuals has increased worldwide. Russia is a country
      with the highest rates of newly diagnosed HIV infections in the region, and the
      infection spreads beyond traditional risk groups. While young women are affected
      disproportionately, knowledge of HIV risk behaviors in women in the general
      population remains limited. The objectives of this study were to identify
      patterns of behaviors that place women of childbearing age at high risk for HIV
      transmission and determine whether socio-demographic characteristics and alcohol
      use are predictive of the risk pattern. A total of 708 non-pregnant women, aged
      between 18 and 44 years, who were at risk for an alcohol-exposed pregnancy were
      enrolled in two regions in Russia. Participants completed a structured interview
      focused on HIV risk behaviors, including risky sexual behavior and alcohol and
      drug use. Latent class analysis was utilized to examine associations between HIV
      risk and other demographic and alcohol use characteristics and to identify
      patterns of risk among women. Three classes were identified. 34.93% of
      participants were at high risk, combining their risk behaviors, e.g., having
      multiple sexual partners, with high partner's risk associated with partner's drug
      use (class I). Despite reporting self-perceived risk for HIV/STI, this class of
      participants was unlikely to utilize adequate protection (i.e., condom use). The
      second high risk class included 13.19% of participants who combined their risky
      sexual behaviors, i.e., multiple sexual partners and having STDs, with partner's
      risk that included partner's imprisonment and partner's sex with other women
      (class II). Participants in this class were likely to utilize protection/condoms.
      Finally, 51.88% of participants were at lower risk, which was associated
      primarily with their partners' risk, and these participants utilized protection
      (class III). The odds of being in class I compared with class III were 3.3 (95%
      CI [1.06, 10.38]) times higher for those women who had Alcohol Use Disorders
      Identification Test scores >= 8 than those who had lower scores, and were 3.9
      (95% CI [1.69, 8.97]) times higher for those who used alcohol before sex than
      those who did not. In addition, women who drank more days per week were 1.36
      times more likely to be in class II than in class III. The study informs
      prevention by identifying specific population groups and targets for
      interventions. Alcohol use is a significant predictor and an overarching factor
      of HIV risk in women. Since at-risk drinking is common among young Russian women,
      alcohol risk reduction should be an essential component of HIV prevention
      efforts.

PMID- 29047001
TI  - In vitro bond strength of an epoxy resin-based root canal sealer to root dentin
      irradiated with high-power lasers and adhesive interface analyses.
AB  - The aim of this study was to evaluate in vitro the influence of high-power lasers
      (Nd:YAG and diode 980 nm) associated with mineral coal as fotopotencializer on
      bond strength of an epoxy resin-based root canal sealer to root dentin, using the
      pushout test, and on the dentin/filling material interface, using confocal laser
      microscopy. For this purposes, 50 canines were instrumented with Mtwo rotary
      system up to #50.04 instrument and randomly assigned to five groups (n = 10):
      group I-control EDTAC; group II-EDTAC and Nd:YAG laser; group III-EDTAC and diode
      laser 980 nm; group IV-EDTAC, Nd:YAG laser and mineral coal 5 g/100 mL; and group
      V-EDTAC, diode laser 980 nm and mineral coal 5 g/100 mL. All data were analyzed
      by ANOVA (at 5% significance level) following the Kruskal-Wallis, Dunn and Tukey
      tests. The group I increased more bond strength of the sealer to root dentin that
      treated with only EDTAC 17% (17.21 +/- 21.75 MPa), similar to the group II (12.21
      +/- 18.20 MPa) and group IV (14.92 +/- 28.06 MPa), both treated with Nd:YAG
      laser, with the exception of group IV, which was added to mineral coal. The group
      V (8.75 +/- 13.42 MPa) had similar results to the groups II and IV, but the same
      similarity were found when compared with group III (7.11 + 11.28 MPa), with lower
      results. Regarding the root thirds, the apical third (23.27 +/- 29.21 MPa)
      presented a statistically higher value on bond strength than the cervical third
      (5.92 +/- 5.33 MPa) and middle third (6.93 +/- 7, 11 MPa) (p > 0.05). Group II
      (86.27 MUm) showed the highest tags penetration values, with a statistically
      difference to the group III (51.57 MUm), IV (36.77 MUm) and V (32.37 MUm) (p <
      0.05). Group I (71.63 MUm) was statistically similar to groups II and III (p >
      0.05). Group IV had the lowest values and was statistically similarity to groups
      III and V (p > 0.05). It was concluded that the treatment with Nd:YAG laser
      provides better results than the diode 980 nm laser, except when was added
      mineral coal. The control and diode 980 nm laser groups presented less adhesive
      failures and more mists failures than the other groups. Both lasers did not
      interfere negatively compared to the control group.

PMID- 29047002
TI  - Treatment of keloid scars using light-, laser- and energy-based devices: a
      contemporary review of the literature.
AB  - Keloid scars are common and have a predilection for young, ethnic skin often with
      a family history. Keloids can be painful and pruritic and cause significant
      emotional distress when particularly visible or prominent. In this article, we
      review the evidence underlying the use of laser- and energy-based devices for
      treatment of keloid scars, either as monotherapy or in conjunction with other
      therapies such as corticosteroids, surgery and silicone gel in the treatment of
      keloid scars.

PMID- 29047005
TI  - Identification of valve-related artifact during cardiac mapping.
AB  - PURPOSE: During cardiac mapping, it is critical to discriminate signals related
      to cardiac conduction versus those due to mechanical interaction with other
      cardiac structures such as valves. We sought to define characteristics that could
      facilitate discrimination of valve artifact from cardiac conduction signals.
      METHODS: Patients with structurally normal heart undergoing mapping for
      ventricular arrhythmias arising from the vicinity of the aortic valve between
      January 2013 and May 2015 were included. Potentials felt to reflect aortic valve
      opening (occurring at the end of the QRS after the local ventricular signal) were
      termed A1, and those felt to reflect valve closure were termed A2. RESULTS: A
      total of 24 patients had mapping in the sinuses of Valsalva, and 10 (average age
      40 + 15, 60% male) were found to have additional signals (A1 and/or A2) notable
      during mapping. In all patients, intervals between A1 and A2 shortened after
      ectopic beats and lengthened after compensatory pauses. These variations in the
      interval matched the change in systolic duration on Doppler echocardiography.
      Overdrive atrial pacing was performed in four patients, which demonstrated
      progressive shortening of intervals between A1 and A2. Pacing always revealed
      local capture without affecting A1 or A2. In the one patient in whom ablation was
      performed in these areas, there was no effect on A1 or A2, suggesting these
      signals represented artifact. CONCLUSIONS: Valve-related signals in the aortic
      sinuses are commonly seen and can be distinguished. The interval between A1 and
      A2 correlated with mechanical systole and varied in a physiologically predictable
      manner with heart rate changes.

PMID- 29047004
TI  - Age Patterns in Risk Taking Across the World.
AB  - Epidemiological data indicate that risk behaviors are among the leading causes of
      adolescent morbidity and mortality worldwide. Consistent with this, laboratory
      based studies of age differences in risk behavior allude to a peak in
      adolescence, suggesting that adolescents demonstrate a heightened propensity, or
      inherent inclination, to take risks. Unlike epidemiological reports, studies of
      risk taking propensity have been limited to Western samples, leaving questions
      about the extent to which heightened risk taking propensity is an inherent or
      culturally constructed aspect of adolescence. In the present study, age patterns
      in risk-taking propensity (using two laboratory tasks: the Stoplight and the
      BART) and real-world risk taking (using self-reports of health and antisocial
      risk taking) were examined in a sample of 5227 individuals (50.7% female) ages 10
      30 (M = 17.05 years, SD = 5.91) from 11 Western and non-Western countries (China,
      Colombia, Cyprus, India, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand,
      and the US). Two hypotheses were tested: (1) risk taking follows an inverted-U
      pattern across age groups, peaking earlier on measures of risk taking propensity
      than on measures of real-world risk taking, and (2) age patterns in risk taking
      propensity are more consistent across countries than age patterns in real-world
      risk taking. Overall, risk taking followed the hypothesized inverted-U pattern
      across age groups, with health risk taking evincing the latest peak. Age patterns
      in risk taking propensity were more consistent across countries than age patterns
      in real-world risk taking. Results suggest that although the association between
      age and risk taking is sensitive to measurement and culture, around the world,
      risk taking is generally highest among late adolescents.

PMID- 29047006
TI  - Extended culture of poor-quality supernumerary embryos improves ART outcomes.
AB  - PURPOSE: The aims of this study were to investigate the possible benefits of
      extending the culture of poor-quality day-2 embryos (PQE) versus good-quality
      embryos (GQE) and to identify factors associated with pregnancy and live birth
      when transferring frozen-thawed blastocysts originating from GQE and PQE.
      METHODS: This is a retrospective cohort follow-up study performed between
      November 2012 and February 2015 at the IVF Laboratory Unit of Cochin University
      Hospital (Paris, France) including 3108 day-2 supernumerary embryos resulting
      from 1237 IVF/ICSI cycles. RESULTS: Total blastulation rate was 67.2% from GQE
      and 48.7% from PQE. Percentage of good-quality blastocysts was 60.7 and 47.9%
      respectively including 14.7 and 7.3% top-quality blastocysts. A total of 150
      blastocysts originating from GQE and 729 from PQE were frozen, and then, 37 and
      164 were thawed and transferred respectively resulting in 19 (51.4%) and 61
      (37.9%) clinical pregnancies with 13 (35.1%) deliveries from GQE and 32 (19.9%)
      from PQE (p = 0.046) without any difference in neonatal outcomes. Quality of
      blastocysts that resulted in live birth was similar in the two groups. Women < 35
      years old and day-5 blastocyst expansion were predictive of pregnancy and live
      birth. CONCLUSIONS: (i) PQE are able to reach the blastocyst stage, to implant,
      and to give healthy babies and (ii) women age and day of blastocyst expansion are
      predictive of pregnancy and live birth.

PMID- 29047007
TI  - Author Correction: Association between G1733A (rs6152) polymorphism in androgen
      receptor gene and recurrent spontaneous abortions in Mexican population.
AB  - The original version of this article unfortunately contained two mistakes in the
      Abstract and the Discussion sections that the authors would like to correct.

PMID- 29047008
TI  - Pastoralists' knowledge and practices towards clinical bovine dermatophilosis in
      cattle herds of North-Central Nigeria: the associated factors, burden and
      economic impact.
AB  - Dermatophilosis is a contagious disease of high economic importance. The study
      assessed knowledge/awareness and clinical burden of and mitigation measures
      practised against clinical bovine dermatophilosis in pastoral herds of North
      Central Nigeria and associated socio-cultural factors that predisposed to its
      occurrence in herds. A cross-sectional survey was conducted between October 2015
      and September 2016. Questionnaires were administered on pastoralists and clinical
      assessment of cattle with gross pathological lesions indicative of
      dermatophilosis conducted. Associated economic impact was estimated. All 384
      selected pastoralists participated in the survey. The majorities of nomadic
      (97.4%) and sedentary (68.2%) pastoralists significantly (p < 0.05) reported to
      have heard about dermatophilosis. Majorities of the sedentary (91.7%) and nomadic
      (97.4%) pastoralists mentioned the use antibiotics to manage the disease.
      Pastoralists in age group 70-79 years were more likely (OR 15.22; 95% CI 4.69,
      49.34) to possess satisfactory knowledge about the disease. Culture of giving out
      cattle as gift or payment for dowry was more likely (OR 28.56; 95% CI 15.64,
      52.12) to influence dermatophilosis occurrence in herds. Overall clinical
      dermatophilosis burden was 3.6% (95% CI 3.46, 3.80) and the annual economic
      impact was estimated at 908,463.9 USD. This study has given an idea to the status
      of pastoralists' levels of awareness about dermatophilosis in Nigeria, which can
      be harnessed by policy makers to develop its mitigation measures. Significant
      influence of pastoralists' socio-cultural activities on dermatophilosis
      occurrence in herds was identified. Surveillance and control programmes towards
      dermatophilosis that take these factors into consideration will be beneficial to
      the herders.

PMID- 29047009
TI  - Correction to: First confirmation of rabies in Zamfara State, Nigeria-in a sheep.
AB  - Unfortunately the Abstract was missing in the original version of this article.
      The Abstract is published below.

PMID- 29047010
TI  - Disrupted cholinergic modulation can underlie abnormal gamma rhythms in
      schizophrenia and auditory hallucination.
AB  - The pathophysiology of auditory hallucination, a common symptom of schizophrenia,
      has yet been understood, but during auditory hallucination, primary auditory
      cortex (A1) shows paradoxical responses. When auditory stimuli are absent, A1
      becomes hyperactive, while A1 responses to auditory stimuli are reduced. Such
      activation pattern of A1 responses during auditory hallucination is consistent
      with aberrant gamma rhythms in schizophrenia observed during auditory tasks,
      raising the possibility that the pathology underlying abnormal gamma rhythms can
      account for auditory hallucination. Moreover, A1 receives top-down signals in the
      gamma frequency band from an adjacent association area (Par2), and cholinergic
      modulation regulates interactions between A1 and Par2. In this study, we utilized
      a computational model of A1 to ask if disrupted cholinergic modulation could
      underlie abnormal gamma rhythms in schizophrenia. Furthermore, based on our
      simulation results, we propose potential pathology by which A1 can directly
      contribute to auditory hallucination.

PMID- 29047011
TI  - Comparing pharmacophore models derived from crystallography and NMR ensembles.
AB  - NMR and X-ray crystallography are the two most widely used methods for
      determining protein structures. Our previous study examining NMR versus X-Ray
      sources of protein conformations showed improved performance with NMR structures
      when used in our Multiple Protein Structures (MPS) method for receptor-based
      pharmacophores (Damm, Carlson, J Am Chem Soc 129:8225-8235, 2007). However, that
      work was based on a single test case, HIV-1 protease, because of the rich data
      available for that system. New data for more systems are available now, which
      calls for further examination of the effect of different sources of protein
      conformations. The MPS technique was applied to Growth factor receptor bound
      protein 2 (Grb2), Src SH2 homology domain (Src-SH2), FK506-binding protein 1A
      (FKBP12), and Peroxisome proliferator-activated receptor-gamma (PPAR-gamma).
      Pharmacophore models from both crystal and NMR ensembles were able to
      discriminate between high-affinity, low-affinity, and decoy molecules. As we
      found in our original study, NMR models showed optimal performance when all
      elements were used. The crystal models had more pharmacophore elements compared
      to their NMR counterparts. The crystal-based models exhibited optimum performance
      only when pharmacophore elements were dropped. This supports our assertion that
      the higher flexibility in NMR ensembles helps focus the models on the most
      essential interactions with the protein. Our studies suggest that the "extra"
      pharmacophore elements seen at the periphery in X-ray models arise as a result of
      decreased protein flexibility and make very little contribution to model
      performance.

PMID- 29047014
TI  - A Callosal Catastrophe: Toxic Leukoencephalopathy Associated with Thermogenic
      Weight Loss Supplement Use.
AB  - BACKGROUND: The use of weight loss drugs and dietary supplements is common, but
      safety profiles for these drugs are largely unknown. Reports of toxicity have
      been published, and the use of these agents should be considered in clinical
      differential diagnoses. METHODS: We report the case of a patient with toxic
      leukoencephalopathy and hyponatremia associated with oral consumption of a
      thermogenic dietary supplement and essential oils. RESULTS: A 30-year-old woman
      presented after 2 days of headache, blurred vision, photophobia, vomiting, and
      hand spasms. She was taking a thermogenic dietary supplement daily for 6 months
      as well as a number of essential oils. Examination revealed mild right sided
      ataxia and diffuse hyperreflexia. Neuroimaging demonstrated bilaterally symmetric
      T2 hyperintensities of the corpus callosum and periventricular white matter.
      Approximately 18 h after admission she became unresponsive with brief extensor
      posturing and urinary incontinence. She partially recovered, but 1 h later became
      unresponsive with dilated nonreactive pupils and extensor posturing (central
      herniation syndrome). She was intubated, hyperventilated, and given hyperosmotic
      therapy. Emergent imaging showed diffuse cerebral edema. Intracranial pressure
      was elevated but normalized with treatment; she regained consciousness the
      following day. She was extubated one day later and discharged on hospital day 5.
      She was seen 2 months later with no further symptoms and a normal neurologic
      examination. CONCLUSIONS: The pathophysiology of this patient's hyponatremia and
      toxic leukoencephalopathy is unknown. However, physicians must be aware of the
      association between thermogenic dietary supplements and toxic
      leukoencephalopathy. Vigilance for life-threatening complications including
      hyponatremia and cerebral edema is critical.

PMID- 29047012
TI  - Chronic curcumin treatment improves spatial working memory but not recognition
      memory in middle-aged rhesus monkeys.
AB  - Studies of both humans and non-human primates have demonstrated that aging is
      typically characterized by a decline in cognition that can occur as early as the
      fifth decade of life. Age-related changes in working memory are particularly
      evident and mediated, in part, by the prefrontal cortex, an area known to
      evidence age-related changes in myelin that is attributed to inflammation. In
      recent years, several nutraceuticals, including curcumin, by virtue of their anti
      inflammatory and antioxidant effects, have received considerable attention as
      potential treatments for age-related cognitive decline and inflammation.
      Accordingly, we assessed for the first time in a non-human primate model of
      normal aging the efficacy of dietary intervention using the natural phenol
      curcumin to ameliorate the effects of aging on spatial working and recognition
      memory. Results revealed that monkeys receiving daily administration of curcumin
      over 14-18 months demonstrated a greater improvement in performance on repeated
      administration of a task of spatial working memory compared to monkeys that
      received a control substance.

PMID- 29047015
TI  - Quality of Online Resources for Pancreatic Cancer Patients.
AB  - The Internet is increasingly a source of information for pancreatic cancer
      patients. This disease is usually diagnosed at an advanced stage; therefore,
      timely access to high-quality information is critical. Our purpose is to
      systematically evaluate the information available to pancreatic cancer patients
      on the internet. An internet search using the term "pancreatic cancer" was
      performed, with the meta-search engines "Dogpile", "Yippy" and "Google". The top
      100 websites returned by the search engines were evaluated using a validated
      structured rating tool. Inter-rater reliability was evaluated using kappa
      statistics and results were analyzed using descriptive statistics. Amongst the
      100 websites evaluated, etiology/risk factors and symptoms were the most
      accurately covered (70 and 67% of websites). Prevention, treatment and prognosis
      were the least accurate sections (55, 55 and 43% of websites). Prevention and
      prognosis were also the least likely to be covered with 63 and 51 websites
      covering these, respectively. Only 40% of websites identified an author. Twenty
      two percent of websites were at a university reading level. The majority of
      online information is accurate but incomplete. Websites may lack information on
      prognosis. Many websites are outdated and lacked author information, and
      readability levels are inappropriate. This knowledge can inform the dialogue
      between healthcare providers and patients.

PMID- 29047013
TI  - Behavioral Animal Model of the Emotional Response to Tinnitus and Hearing Loss.
AB  - Increased prevalence of emotional distress is associated with tinnitus and
      hearing loss. The underlying mechanisms of the negative emotional response to
      tinnitus and hearing loss remain poorly understood, and it is challenging to
      disentangle the emotional consequences of hearing loss from those specific to
      tinnitus in listeners experiencing both. We addressed these questions in
      laboratory rats using three common rodent anxiety screening assays: elevated plus
      maze, open field test, and social interaction test. Open arm activity in the
      elevated plus maze decreased substantially after one trial in controls,
      indicating its limited utility for comparing pre- and post-treatment behavior.
      Open field exploration and social interaction behavior were consistent across
      multiple sessions in control animals. Individual sound-exposed and salicylate
      treated rats showed a range of phenotypes in the open field, including reduced
      entries into the center in some subjects and reduced locomotion overall. In rats
      screened for tinnitus, less locomotion was associated with higher tinnitus
      scores. In salicylate-treated animals, locomotion was correlated with age. Sound
      exposed and salicylate-treated rats also showed reduced social interaction. These
      results suggest that open field exploratory activity is a selective measure for
      identifying tinnitus distress in individual animals, whereas social interaction
      reflects the general effects of hearing loss. This animal model will facilitate
      future studies of the structural and functional changes in the brain pathways
      underlying emotional distress associated with hearing dysfunction, as well as
      development of novel interventions to ameliorate or prevent negative emotional
      responses.

PMID- 29047016
TI  - The Impact of Peritumoral Retraction Clefting & Intratumoral Eosinophils on
      Overall Survival in Oral Squamous Carcinoma Patients.
AB  - This retrospective study aimed to investigate the impact of peritumoral
      retraction clefts (RC) and tumor-associated tissue eosinophilia (TATE) as
      predictors of overall survival (OS) in oral squamous cell carcinoma (OSCC)
      patients. Their relationships with tumor-factors were also examined. Eighty-seven
      OSCC cases (pTNM: I + II/III + IV; 32/55), post-curative surgery, comprised the
      study cohort. Three observers independently estimated the percent RC semi
      quantitatively in the selected tumor sections. Additionally, stromal eosinophils
      were counted in ten consecutive high-power fields of intratumoral and peritumoral
      regions to evaluate the corresponding TATE. The percent RC ranged between 0% -90%
      (Mean +/- SD: 16 +/- 24%; Median: 5%). The stromal eosinophils were greater in
      peritumoral as compared to intratumoral region. The events of death and tumor
      recurrence were reached in 16 (18.4%) and 36 (41%) cases respectively. The 3
      years OS was 69% [Median OS: 1880 days; Mean follow up: 471(Range; 36-1880)
      days]. Increased percent RC exhibited relationship with pathologic stage (pTNM
      III&IV), primary tumor (pT III&IV), tumor depth > 4 mm and categorical tumor
      recurrence. Additionally, peritumoral eosinophilic infiltrates increased with
      increasing tumor depths and muscle invasion. Kaplan-Meier curves revealed
      significantly reduced OS in OSCC cases exhibiting: increased percent RC (>2.5%),
      mild -moderate/absent intratumoral TATE (versus intense TATE) or categorical
      tumor recurrence. In subsequent multivariate tests, all the three variables
      retained significance. Additionally, intraclass correlation coefficient
      demonstrated acceptable internal consistency for the observers who estimated
      percent RC. In conclusion, RC and intratumoral TATE proved to be independent
      predictors of OS in our OSCC cohort. Additionally, increased percent RC pointed
      towards aggressive tumor behaviour.

PMID- 29047017
TI  - Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations
      Containing Sugars and Polyol: 1-Formulation Development.
AB  - L-arginine was introduced into protein-based freeze-dried formulations to study
      the ability of arginine to reduce/prevent from protein aggregation during
      manufacturing, storage and reconstitution of lyophilized protein-based
      pharmaceuticals. As L-arginine is known to be very hygroscopic, additional
      excipients which could provide a moisture buffering capacity need to be
      introduced into the formulation. In the first part of our study-excipient
      formulation development-the screening of a number of sugars/polyols has been done
      in order to select the best combination of excipients that, in a complex with L
      arginine, can (i) produce freeze-dried cakes with elegant appearance, adequate
      mechanical properties and reconstitution times, and (ii) resist/minimise the
      moisture sorption. Various freeze-dried cakes containing L-arginine in
      combination with mannitol, trehalose, lactose and sucrose were produced and
      analysed by TGA, DSC, texture analysis, moisture sorption, cake shrinkage, TVIM
      and SEM. The non-linear dependencies of the physicochemical properties of the
      freeze-dried cakes on the sugar-to-mannitol ratios were found. The best
      combinations of excipients (L-arginine, mannitol and trehalose) were selected to
      be used in the second part of this work, in which the impact of each selected
      formulation will be studied in relation to the aggregation of a protein.

PMID- 29047018
TI  - Identification of a novel torque teno mini virus in cerebrospinal fluid from a
      child with encephalitis.
AB  - Anelloviruses are single-strand circular DNA viruses and ubiquitous within the
      human population. Although there is no direct evidence, many studies have
      suggested the anelloviruses may be associated with a variety of diseases. In this
      study, a novel torque teno mini virus (TTMV) was detected in a child with
      unexplained encephalitis. The detected virus had a circular genome of 2943 nt in
      length and 3 open reading frames. It shared 45.4% - 35.9% nucleotide identities
      with known TTMV species and < 35% with the other species of anellovirus, which
      suggested it might belong to a new species within the genus Betatorquevirus.
      Phylogenetic analysis based on the amino acid sequences of ORF1 showed that this
      virus represented a distinct branch within the diversity of anellovirus. Whether
      this novel anellovirus strain is associated with encephalitis requires further
      study.

PMID- 29047019
TI  - Challenges for nationwide vaccine delivery in African countries.
AB  - Vaccines are very effective in providing individual and community (herd) immunity
      against a range of diseases. In addition to protection against a range of
      diseases, vaccines also have social and economic benefits. However, for vaccines
      to be effective, routine immunization programmes must be undertaken regularly to
      ensure individual and community protection. Nonetheless, in many countries in
      Africa, vaccination coverage is low because governments struggle to deliver
      vaccines to the most remote areas, thus contributing to constant outbreaks of
      various vaccine-preventable diseases. African governments fail to deliver
      vaccines to a significant percentage of the target population due to many issues
      in key areas such as policy setting, programme management and financing, supply
      chain, global vaccine market, research and development of vaccines. This review
      gives an overview of the causes of these issues and what is currently being done
      to address them. This review will discuss the role of philanthropic organisations
      such as the Bill and Melinda Gates Foundation and global partnerships such as the
      global alliance for vaccines and immunizations in the development, purchase and
      delivery of vaccines.

PMID- 29047021
TI  - The Influence of Constructed Family Membership on HIV Risk Behaviors among Gay,
      Bisexual, and Other Men Who Have Sex with Men in New Orleans.
AB  - Gay, bisexual, and other men who have sex with men (MSM) represent more new HIV
      infections than all other at-risk populations. Many young black MSM belong to
      constructed families (i.e., the house ball community, gay families, and pageant
      families) which are often organized in a family structure with members referred
      to as parents and children. Many constructed families are associated with a
      family surname which is informally adopted by members. In some cases, however,
      constructed families do not identify with a collective family name. In 2014, 553
      MSM were recruited through venue-based time-space sampling during the National
      HIV Behavioral Surveillance (NHBS) in New Orleans to complete a structured survey
      and HIV test. Black, Latino, and other race MSM were more likely to belong to
      constructed families in comparison to white MSM. In addition, participants who
      belonged to constructed families with a family name were more likely to engage in
      protective behaviors including wearing condoms at last sexual intercourse.
      Overall, younger, white MSM who did not belong to any social groups were more
      likely to engage in at least one risk behavior. These findings significantly
      contribute to understanding variations in HIV risk behavior among members of
      constructed families.

PMID- 29047022
TI  - Training for Data Science: Imagine There's no Countries.

PMID- 29047023
TI  - Heparin-binding protein (HBP) improves prediction of sepsis-related acute kidney
      injury.
AB  - BACKGROUND: Sepsis-related acute kidney injury (AKI) accounts for major morbidity
      and mortality among the critically ill. Heparin-binding protein (HBP) is a
      promising biomarker in predicting development and prognosis of severe sepsis and
      septic shock that has recently been proposed to be involved in the
      pathophysiology of AKI. The objective of this study was to investigate the added
      predictive value of measuring plasma HBP on admission to the intensive care unit
      (ICU) regarding the development of septic AKI. METHODS: We included 601 patients
      with severe sepsis or septic shock from the prospective, observational FINNAKI
      study conducted in seventeen Finnish ICUs during a 5-month period (1 September
      2011-1 February 2012). The main outcome measure was the development of KDIGO AKI
      stages 2-3 from 12 h after admission up to 5 days. Statistical analysis for the
      primary endpoint included construction of a clinical risk model, area under the
      receiver operating curve (ROC area), category-free net reclassification index
      (cfNRI) and integrated discrimination improvement (IDI) with 95% confidence
      intervals (95% CI). RESULTS: Out of 511 eligible patients, 101 (20%) reached the
      primary endpoint. The addition of plasma HBP to a clinical risk model
      significantly increased ROC area (0.82 vs. 0.78, p = 0.03) and risk
      classification scores: cfNRI 62.0% (95% CI 40.5-82.4%) and IDI 0.053 (95% CI
      0.029-0.075). CONCLUSIONS: Plasma HBP adds predictive value to known clinical
      risk factors in septic AKI. Further studies are warranted to compare the
      predictive performance of plasma HBP to other novel AKI biomarkers.

PMID- 29047020
TI  - Rotavirus epidemiology and vaccine demand: considering Bangladesh chapter through
      the book of global disease burden.
AB  - BACKGROUND: Rotavirus is the major cause of gastroenteritis in children
      throughout the world. Every year, a large number of children aged < 5 years die
      from rotavirus-related diarrhoeal diseases. Though these infections are vaccine
      preventable, the vast majority of children in low-income countries suffer from
      the infection. The situation leads to severe economic loss and constitutes a
      major public health problem. METHODS: We searched electronic databases including
      PubMed and Google scholar using the following words: "features of rotavirus,"
      "epidemiology of rotavirus," "rotavirus serotypes," "rotavirus in Bangladesh,"
      "disease burden of rotavirus," "rotavirus vaccine," "low efficacy of rotavirus
      vaccine," "inactivated rotavirus vaccine". Publications until July 2017 have been
      considered for this work. RESULTS AND CONCLUSION: Currently, two live attenuated
      vaccines are available throughout the world. Many countries have included
      rotavirus vaccines in national immunization program to reduce the disease burden.
      However, due to low efficacy of the available vaccines, satisfactory outcome has
      not yet been achieved in developing countries such as Bangladesh. Poor economic,
      public health, treatment, and sanitation status of the low-income countries
      necessitate the need for the most effective rotavirus vaccines. Therefore, the
      present scenario demands the development of a highly effective rotavirus vaccine.
      In this regard, inactivated rotavirus vaccine concept holds much promise for
      reducing the current disease burden. Recent advancements in developing an
      inactivated rotavirus vaccine indicate a significant progress towards disease
      prophylaxis and control.

PMID- 29047024
TI  - Generation of Photoreceptor Precursors from Mouse Embryonic Stem Cells.
AB  - Embryonic stem cell (ESC) differentiation can be used to model development and to
      produce transplantable cells of the desired phenotype. ESCs can reproducibly
      generate retinal cells but the derivation of photoreceptor precursors is variable
      and depends on an array of exogenous factors and intrinsic cell-cell
      interactions. In this work, we have defined the use of exogenous signaling
      factors, dissociation, and adherent versus 3-dimensional (3D) conditions on the
      derivation of retinal cells from pluripotent mouse ESCs. Differentiation
      protocols were chosen based on the developmental stage and cell population of
      interest and evaluated by expression of developmental stage- and lineage-specific
      marker genes. We present a relatively simple protocol that guides differentiating
      ESCs through stages that correspond to the sequence of in vivo developmental
      events and is optimized for studying the time frame between eye field formation
      and photoreceptor precursor development in the equivalent of embryonic retina.
      Step-wise exposure of adherent cultures to exogenous factors facilitated
      expression of eye field transcription factors and limited non-specific
      differentiation. Dissociation after the establishment of eye field and retinal
      progenitor cell gene expression did not cause substantial loss in expression of
      markers of mature photoreceptors. Finally, 3D organoids improved expression of
      photoreceptor genes and region-specific architecture but required more technical
      manipulation. We demonstrate the usefulness of this ESC-retinal induction
      protocol in screening for factors that improve photoreceptor precursor yield by
      evaluating response to alterations in Activin signaling.

PMID- 29047026
TI  - An observation that illustrates most T cell receptor structure-function
      relationships.
AB  - The Standard model of the T cell receptor (TCR) structure-function relationships
      is based on an analogy with the B cell receptor. Here a single observation is
      analyzed to show why this appears to be untenable. The Standard model cannot
      account for allele-specific recognition of theMHC-encoded presenter of peptide
      (R) by the TCR nor can it adequately explain alloreactivity. The competing
      framework is based on the assumptions that (1) single V-domains recognize the
      alleles of R, (2) restrictive reactivity is peptide specific, whereas
      alloreactivity is peptide unspecific, and (3) the TCR is born in two
      conformations, which display reciprocal behaviors (see text). In any case,
      whatever position one takes regarding these two models, competing
      conceptualizations are of crucial value in guiding experimentation, not to
      mention creative thinking.

PMID- 29047027
TI  - A possible mechanism for low affinity of silkworm Na+/K+-ATPase for K.
AB  - The affinity for K+ of silkworm nerve Na+/K+-ATPase is markedly lower than that
      of mammalian Na+/K+-ATPase (Homareda 2010). In order to obtain clues on the
      molecular basis of the difference in K+ affinities, we cloned cDNAs of silkworm
      (Bombyx mori) nerve Na+/K+-ATPase alpha and beta subunits, and analyzed the
      deduced amino acid sequences. The molecular masses of the alpha and beta subunits
      were presumed to be 111.5 kDa with ten transmembrane segments and 37.7 kDa with a
      single transmembrane segment, respectively. The alpha subunit showed 75% identity
      and 93% homology with the pig Na+/K+-ATPase alpha1 subunit. On the other hand,
      the amino acid identity of the beta subunit with mammalian counterparts was as
      low as 30%. Cloned alpha and beta cDNAs were co-expressed in cultured silkworm
      ovary-derived cells, BM-N cells, which lack endogenous Na+/K+-ATPase. Na+/K+
      ATPase expressed in the cultured cells showed a low affinity for K+ and a high
      affinity for Na+, characteristic of the silkworm nerve Na+/K+-ATPase. These
      results suggest that the beta subunit is responsible for the affinity for K+ of
      Na+/K+-ATPase.

PMID- 29047025
TI  - Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel
      inhibitors from nature and drug repurposing.
AB  - In the past 15 years, the proteasome has been validated as an anti-cancer drug
      target and 20S proteasome inhibitors (such as bortezomib and carfilzomib) have
      been approved by the FDA for the treatment of multiple myeloma and some other
      liquid tumors. However, there are shortcomings of clinical proteasome inhibitors,
      including severe toxicity, drug resistance, and no effect in solid tumors. At the
      same time, extensive research has been conducted in the areas of natural
      compounds and old drug repositioning towards the goal of discovering effective,
      economical, low toxicity proteasome-inhibitory anti-cancer drugs. A variety of
      dietary polyphenols, medicinal molecules, metallic complexes, and metal-binding
      compounds have been found to be able to selectively inhibit tumor cellular
      proteasomes and induce apoptotic cell death in vitro and in vivo, supporting the
      clinical success of specific 20S proteasome inhibitors bortezomib and
      carfilzomib. Therefore, the discovery of natural proteasome inhibitors and
      researching old drugs with proteasome-inhibitory properties may provide an
      alternative strategy for improving the current status of cancer treatment and
      even prevention.

PMID- 29047028
TI  - De novo implantation vs. upgrade cardiac resynchronization therapy: a systematic
      review and meta-analysis.
AB  - : Patients with conventional pacemakers or implanted defibrillators are often
      considered for cardiac resynchronization therapy (CRT). Our aim was to summarize
      the available evidences regarding the clinical benefits of upgrade procedures. A
      systematic literature search was performed from studies published between 2006
      and 2017 in order to compare the outcome of CRT upgrade vs. de novo
      implantations. Outcome data on all-cause mortality, heart failure events, New
      York Heart Association (NYHA) Class, QRS narrowing and echocardiographic
      parameters were analysed. A total of 16 reports were analysed comprising 489,568
      CRT recipients, of whom 468,205 patients underwent de novo and 21,363 upgrade
      procedures. All-cause mortality was similar after CRT upgrade compared to de novo
      implantations (RR 1.19, 95% CI 0.88-1.60, p = 0.27). The risk of heart failure
      was also similar in both groups (RR 0.96, 95% CI 0.70-1.32, p = 0.81). There was
      no significant difference in clinical response after CRT upgrade compared to de
      novo implantations in terms of improvement in left ventricular ejection fraction
      (DeltaEF de novo - 6.85% vs. upgrade - 9.35%; p = 0.235), NYHA class (DeltaNYHA
      de novo - 0.74 vs. upgrade - 0.70; p = 0.737) and QRS narrowing (DeltaQRS de novo
      - 9.6 ms vs. upgrade - 29.5 ms; p = 0.485). Our systematic review and meta
      analysis of currently available studies reports that CRT upgrade is associated
      with similar risk for all-cause mortality compared to de novo resynchronization
      therapy. Benefits on reverse remodelling and functional capacity improved
      similarly in both groups suggesting that CRT upgrade may be safely and
      effectively offered in routine practice. CLINICAL TRIAL REGISTRATION: Prospero
      Database-CRD42016043747.

PMID- 29047030
TI  - Representational momentum and anisotropies in nearby visual space.
AB  - The possibility of anisotropies in visual space in and near the final location of
      a moving target was examined. Experiments 1 and 2 presented a moving target, and
      after the target vanished, participants indicated the final location of the
      leading or trailing edge of the target. Memory for both edges was displaced
      forward from the actual final locations, and the magnitude of displacement was
      smaller for the leading edge. Experiments 3 and 4 also presented stationary
      objects in front of and behind the final location of the target, and participants
      indicated the location of the nearest or farthest edge of one of the stationary
      objects. Memory for the near or far edge of an object in front of the target was
      displaced backward, and memory for the near or far edge of an object behind the
      target was displaced forward; the magnitude of displacement was larger for
      objects in front of the target and when the edge was farther away. The findings
      (a) suggest representational momentum is associated with an anisotropy of visual
      space that extends across and outward from the moving target and (b) are
      consistent with previous findings regarding estimation of time-to-contact,
      anorthoscopic perception, and memory psychophysics.

PMID- 29047029
TI  - Phase I study of the combination of crizotinib (as a MET inhibitor) and dasatinib
      (as a c-SRC inhibitor) in patients with advanced cancer.
AB  - Background Both MET and c-SRC are important mediators of cancer progression and
      there is cross talk between the two molecules. Preclinical studies have
      demonstrated combination of MET and c-SRC inhibitors is effective in multiple
      cancer types. Methods We analyzed the safety and efficacy of administering a c
      SRC inhibitor (dasatinib) in combination with a MET inhibitor (crizotinib) in a
      two-arm concurrent phase I study. Arm A consisted of crizotinib fixed at 250 mg
      twice per day with escalation of dasatinib. Arm B consisted of dasatinib fixed at
      140 mg daily with escalation of crizotinib. Endpoints included dose-limiting
      toxicities (DLTs), recommended phase II dose (RP2D), and response (RECIST 1.1).
      Results We enrolled 61 patients (arm A: 31, arm B: 30). The most common cancers
      were sarcoma (21%) and prostate cancer (16%). In Arm A, at dose level 2 (DL2),
      40% (2/5) experienced DLTs. In the expanded DL1, 21% (4/19) experienced DLTs (all
      grade 3). In Arm B, at DL2, 50% (2/4) experienced DLTs. In the expanded DL1, 22%
      (4/18) experienced DLTs (all grade 3). RP2D was determined to be arm A, DL1 (250
      mg crizotinib orally twice per day plus 50 mg dasatinib orally daily). Partial
      response (N = 1) and stable disease for >=6 months (N = 3) were seen. Conclusions
      The combination of crizotinib and dasatinib is safe to administer but
      tolerability is limited given the high rate of adverse events. Responses and
      durable stable disease were limited. Further precision therapy approach using
      this specific combination may be difficult given the toxicity.

PMID- 29047031
TI  - The effect of phasic alertness on temporal precision.
AB  - Many previous studies have found that there is a close relationship between
      attention and temporal precision. As a mechanism that regulates the intensity of
      attention, alertness has beneficial influences on perceptual processing. However,
      little is known regarding whether and how phasic alertness affects temporal
      precision. Experiment 1 and Experiment 2 used visual and auditory warning cues in
      a visual temporal order judgment (TOJ) task and a simultaneity judgment (SJ) task
      to investigate the phasic alerting effect on temporal precision. Participants in
      the TOJ and SJ tasks were required to make judgments of two successive and
      synchronous stimuli at various stimulus onset asynchronies (SOAs). Because of
      dissension regarding the SJ task, Experiment 3 adopted a dual SJ and TOJ task to
      create a new indicator of participant performance. Although these tasks may
      differ in the cognitive mechanism they involve, they all produced consistently
      decreased just noticeable difference (JND) scores and unaltered point of
      subjective simultaneity (PSS). This suggests that phasic alertness could
      significantly improve participants' temporal precision (reduced JNDs) of visual
      perception, without affecting temporal accuracy (unaltered PSS). We then discuss
      that the alerting effect on temporal sensitivity might be attributed mainly to
      transient arousal rather than temporal expectancy. Furthermore, the analysis of
      response ratios at each SOA could distinguish a heightened temporal precision
      from a reduction of attentional lapses. According to the previous and present
      studies, phasic alertness might simultaneously benefited the early perceptual
      processing and late motor execution of responses.

PMID- 29047032
TI  - Rethinking Skin Lesion Segmentation in a Convolutional Classifier.
AB  - Melanoma is a fatal form of skin cancer when left undiagnosed. Computer-aided
      diagnosis systems powered by convolutional neural networks (CNNs) can improve
      diagnostic accuracy and save lives. CNNs have been successfully used in both skin
      lesion segmentation and classification. For reasons heretofore unclear, previous
      works have found image segmentation to be, conflictingly, both detrimental and
      beneficial to skin lesion classification. We investigate the effect of expanding
      the segmentation border to include pixels surrounding the target lesion.
      Ostensibly, segmenting a target skin lesion will remove inessential information,
      non-lesion skin, and artifacts to aid in classification. Our results indicate
      that segmentation border enlargement produces, to a certain degree, better
      results across all metrics of interest when using a convolutional based
      classifier built using the transfer learning paradigm. Consequently,
      preprocessing methods which produce borders larger than the actual lesion can
      potentially improve classifier performance, more than both perfect segmentation,
      using dermatologist created ground truth masks, and no segmentation altogether.

PMID- 29047033
TI  - Characterization of Pulmonary Nodules Based on Features of Margin Sharpness and
      Texture.
AB  - Lung cancer is the leading cause of cancer-related deaths in the world, and one
      of its manifestations occurs with the appearance of pulmonary nodules. The
      classification of pulmonary nodules may be a complex task to specialists due to
      temporal, subjective, and qualitative aspects. Therefore, it is important to
      integrate computational tools to the early pulmonary nodule classification
      process, since they have the potential to characterize objectively and
      quantitatively the lesions. In this context, the goal of this work is to perform
      the classification of pulmonary nodules based on image features of texture and
      margin sharpness. Computed tomography scans were obtained from a publicly
      available image database. Texture attributes were extracted from a co-occurrence
      matrix obtained from the nodule volume. Margin sharpness attributes were
      extracted from perpendicular lines drawn over the borders on all nodule slices.
      Feature selection was performed by different algorithms. Classification was
      performed by several machine learning classifiers and assessed by the area under
      the receiver operating characteristic curve, sensitivity, specificity, and
      accuracy. Highest classification performance was obtained by a random forest
      algorithm with all 48 extracted features. However, a decision tree using only two
      selected features obtained statistically equivalent performance on sensitivity
      and specificity.

PMID- 29047034
TI  - Quantitative Volumetric K-Means Cluster Segmentation of Fibroglandular Tissue and
      Skin in Breast MRI.
AB  - Mammographic breast density (MBD) is the most commonly used method to assess the
      volume of fibroglandular tissue (FGT). However, MRI could provide a clinically
      feasible and more accurate alternative. There were three aims in this study: (1)
      to evaluate a clinically feasible method to quantify FGT with MRI, (2) to assess
      the inter-rater agreement of MRI-based volumetric measurements and (3) to compare
      them to measurements acquired using digital mammography and 3D tomosynthesis.
      This retrospective study examined 72 women (mean age 52.4 +/- 12.3 years) with
      105 disease-free breasts undergoing diagnostic 3.0-T breast MRI and either
      digital mammography or tomosynthesis. Two observers analyzed MRI images for
      breast and FGT volumes and FGT-% from T1-weighted images (0.7-, 2.0-, and 4.0-mm
      thick slices) using K-means clustering, data from histogram, and active contour
      algorithms. Reference values were obtained with Quantra software. Inter-rater
      agreement for MRI measurements made with 2-mm-thick slices was excellent: for FGT
      %, r = 0.994 (95% CI 0.990-0.997); for breast volume, r = 0.985 (95% CI 0.934
      0.994); and for FGT volume, r = 0.979 (95% CI 0.958-0.989). MRI-based FGT-%
      correlated strongly with MBD in mammography (r = 0.819-0.904, P < 0.001) and
      moderately to high with MBD in tomosynthesis (r = 0.630-0.738, P < 0.001). K
      means clustering-based assessments of the proportion of the fibroglandular tissue
      in the breast at MRI are highly reproducible. In the future, quantitative
      assessment of FGT-% to complement visual estimation of FGT should be performed on
      a more regular basis as it provides a component which can be incorporated into
      the individual's breast cancer risk stratification.

PMID- 29047035
TI  - Application of Super-Resolution Convolutional Neural Network for Enhancing Image
      Resolution in Chest CT.
AB  - In this study, the super-resolution convolutional neural network (SRCNN) scheme,
      which is the emerging deep-learning-based super-resolution method for enhancing
      image resolution in chest CT images, was applied and evaluated using the post
      processing approach. For evaluation, 89 chest CT cases were sampled from The
      Cancer Imaging Archive. The 89 CT cases were divided randomly into 45 training
      cases and 44 external test cases. The SRCNN was trained using the training
      dataset. With the trained SRCNN, a high-resolution image was reconstructed from a
      low-resolution image, which was down-sampled from an original test image. For
      quantitative evaluation, two image quality metrics were measured and compared to
      those of the conventional linear interpolation methods. The image restoration
      quality of the SRCNN scheme was significantly higher than that of the linear
      interpolation methods (p < 0.001 or p < 0.05). The high-resolution image
      reconstructed by the SRCNN scheme was highly restored and comparable to the
      original reference image, in particular, for a *2 magnification. These results
      indicate that the SRCNN scheme significantly outperforms the linear interpolation
      methods for enhancing image resolution in chest CT images. The results also
      suggest that SRCNN may become a potential solution for generating high-resolution
      CT images from standard CT images.

PMID- 29047036
TI  - The Falconoid Luteolin Mitigates the Myocardial Inflammatory Response Induced by
      High-Carbohydrate/High-Fat Diet in Wistar Rats.
AB  - Luteolin is a major component of many medicinal plants and traditional medicines.
      The current study aims at testing its protective effect against high
      carbohydrate/high-fat (HCHF) diet-induced cardiac dysfunction in rats. Male
      Wistar rats were divided into six groups as follows: control group that received
      standard rat chow, group received HCHF diet (~ 30% carbohydrate and 42% fat)
      daily for 16 weeks, and four groups received HCHF diet concurrently with luteolin
      (10, 25, 50 or 100 mg/kg; 10% w/v suspension in 0.9% NaCl) daily from the first
      week by oral gavage. Body weight was measured weekly. At the end of the study,
      histopathological examinations of stained heart sections were carried out. Lipid
      profile, oxidative stress, and cardiac function biomarkers were measured.
      Furthermore, neurohumoral mediators and inflammatory cytokines (TNF-alpha, IL-18)
      were assigned. Results showed a significant improvement in cardiac function,
      tissue integrity, and a decrease in the compensatory neurohumoral mediators by
      luteolin 50 and 100 mg/kg. In addition, a significant (P < 0.05) decrease in
      collagen deposition, fibrosis percentage, lipid peroxidation, and inflammatory
      cells (macrophages and lymphocytes) infiltration was observed. Tested doses of
      luteolin decreased lipid peroxidation and elevated the endogenous antioxidant
      biomarkers (reduced glutathione and superoxide dismutase) significantly (P <
      0.05). Finally, luteolin decreased TNF-alpha and IL-18 (P < 0.001) in a dose
      dependent manner. It can be concluded that luteolin has a cardioprotective effect
      against HCHF diet-induced myocardial inflammation through antioxidant anti
      inflammatory mechanisms.

PMID- 29047037
TI  - Diesel Exhaust Particles and the Induction of Macrophage Activation and
      Dysfunction.
AB  - Diesel exhaust particles (DEP) are an important component of air particulate
      matter, generated from the incomplete combustion of fossil fuel in diesel
      engines. Several epidemiological and experimental data have shown the ability of
      DEP to induce oxidative stress and pro-inflammatory response as mechanisms in
      macrophage activation and dysfunction. Macrophages are very important to immunity
      and immune response due to their ability to phagocyte microbes and parasites.
      They also respond to toxic chemicals, such as DEP, in the environment and studies
      have shown that their functions may be impaired by their exposure to DEP. For
      instance, the ultrafine particles (UFP) of DEP are capable of penetrating deep
      into the lungs and getting deposited in the alveolar component, where they can
      mitigate against the phagocytosis function of the alveolar macrophages. In this
      review, data linking DEP exposure to macrophage activation and dysfunction are
      addressed together with the various mechanisms involved in these DEP-induced
      effects.

PMID- 29047039
TI  - Correction to: Contribution of the MRPS22 variant and a Down mosaic to the
      phenotype.
AB  - In the original publication of the article, the title was incorrectly written as
      "The cerebellum is a common site of affection in Leigh syndrome." The correct
      title is "Contribution of the MRPS22 variant and a Down mosaic to the phenotype."

PMID- 29047038
TI  - The Regulatory Roles of Toll-Like Receptor 4 in Secretions of Type 1/Type 2
      Relative Cytokines by Splenocytes and Dendritic Cells Exposed to Clonorchis
      sinensis Excretory/Secretory Products.
AB  - The roles of TLR4 in mediation of innate immune response and in regulation of
      adaptive immune responses triggered by Clonorchis sinensis remain unknown. In the
      present study, splenocytes derived from C3H/HeN (TLR4 wild ) and C3H/Hej mice
      (TLR4 mut ) that were infected with 45 metacercariae of C. sinensis were
      harvested, then stimulated by C. sinensis excretory/secretory products (ESP) or
      medium (control) for 48 h, respectively. Meanwhile, bone marrow-derived dendritic
      cells (BMDCs) from normal C3H/HeN and C3H/Hej mice were prepared and stimulated
      with medium, ESP, LPS, or ESP+LPS for 24 h, respectively. The supernatants were
      collected, and the concentrations of type 1 and type 2 relative cytokines were
      determined by ELISA. The maturation of BMDCs indicated by surface markers of
      CD80, CD86, and MHC II was evaluated by flow cytometry. The results showed that
      the levels of IFN-gamma, IL-6, TNF-alpha, and IL-10 in the splenocytes from C.
      sinensis-infected TLR4 mut mice were significantly lower than those from TLR4
      wild mice when they were further exposed to ESP. For BMDCs, the productions of
      the cytokines IL-12p70 and IL-10, but not IL-4, in the BMDCs from TLR4 mutation
      mice were predominantly decreased compared with those from TLR4 wild mice when
      the BMDCs were co-stimulated by ESP combined with LPS. Flow cytometry analysis
      showed that ESP could significantly decrease the high levels of CD80, CD86, and
      MHC II which were elevated by LPS. In conclusion, these data suggest that TLR4
      may play a regulatory role in type 1 immune responses during C. sinensis
      infection.

PMID- 29047040
TI  - Proline dehydrogenase gene (PRODH) polymorphisms and schizophrenia
      susceptibility: a meta-analysis.
AB  - Previous studies have been conducted to explore the association between proline
      dehydrogenase gene (PRODH) polymorphisms and schizophrenia (SZ) susceptibility,
      but providing the controversial results. Here we performed this meta-analysis to
      determine whether PRODH variants were associated with SZ risk. Relevant studies
      were screened by retrieving online database PubMed, Web of Science, Embase, China
      National Knowledge Infrastructure (CNKI) and SZGene from inception to December
      2016. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based
      on genotype data or allele frequency to evaluate the strength of this
      association. For rs372055, eleven studies with 3398 SZ patients and 3171 controls
      were included and the results indicated that people carrying the T allele was not
      associated with SZ risk in allele frequency model (C vs T, OR = 1.12, 95%CI =
      0.96-1.32). However, results from subgroup analysis showed a significant
      relationship between rs372055 and SZ risk in dominant genetic model (CC + CT vs
      TT, OR = 1.26, 95% CI = 1.05-1.50) and heterogeneous model (CT vs TT, OR = 1.26,
      95% CI = 1.05-1.52) in Asian, but not in Caucasian. For polymorphisms rs383964,
      rs450046, rs385440 and rs2870983, no associations were found between these
      polymorphisms and SZ susceptibility in allele frequency. This meta-analysis
      suggests that rs372055 (C/T) polymorphism in PRODH gene is associated with
      increased SZ risk only in Asian.

PMID- 29047043
TI  - Uncommon Initial Presentation of Gastric Cancer with Bone Metastases: a Case
      Report.

PMID- 29047041
TI  - A profound computational study to prioritize the disease-causing mutations in
      PRPS1 gene.
AB  - Charcot-Marie-Tooth disease (CMT) is one of the most commonly inherited
      congenital neurological disorders, affecting approximately 1 in 2500 in the US.
      About 80 genes were found to be in association with CMT. The phosphoribosyl
      pyrophosphate synthetase 1 (PRPS1) is an essential enzyme in the primary stage of
      de novo and salvage nucleotide synthesis. The mutations in the PRPS1 gene leads
      to X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5), PRS super activity,
      Arts syndrome, X-linked deafness-1, breast cancer, and colorectal cancer. In the
      present study, we obtained 20 missense mutations from UniProt and dbSNP databases
      and applied series of comprehensive in silico prediction methods to assess the
      degree of pathogenicity and stability. In silico tools predicted four missense
      mutations (D52H, M115 T, L152P, and D203H) to be potential disease causing
      mutations. We further subjected the four mutations along with native protein to
      50 ns molecular dynamics simulation (MDS) using Gromacs package. The resulting
      trajectory files were analyzed to understand the stability differences caused by
      the mutations. We used the Root Mean Square Deviation (RMSD), Radius of Gyration
      (Rg), solvent accessibility surface area (SASA), Covariance matrix, Principal
      Component Analysis (PCA), Free Energy Landscape (FEL), and secondary structure
      analysis to assess the structural changes in the protein upon mutation. Our study
      suggests that the four mutations might affect the PRPS1 protein function and
      stability of the structure. The proposed study may serve as a platform for drug
      repositioning and personalized medicine for diseases that are caused by the PRPS1
      deficiency.

PMID- 29047044
TI  - Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin.
AB  - Exosomes are extracellular microvesicles with a particle size of 30-100 nm and
      carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in
      and-out of the cells suggest that these particles can be exploited as a nano drug
      carrier. In this manuscript, we show that curcumin can be delivered effectively
      using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of
      10% ethanol:acetonitrile (1:1) provided a drug load of 18-24%, and the
      formulation stored at - 80 degrees C was stable for 6 months as determined by
      particle size analysis, drug load, and antiproliferative activity. The uptake of
      exosomes by cancer cells involved caveolae/clathrin-mediated endocytosis. Oral
      administration of exosomal curcumin (ExoCUR) in Sprague-Dawley rats demonstrated
      3-5 times higher levels in various organs versus free agent. ExoCUR showed
      enhanced antiproliferative activity against multiple cancer cell lines including,
      breast, lung, and cervical cancer compared with the free curcumin. ExoCUR showed
      significantly higher anti-inflammatory activity measured as NF-kappaB activation
      in human lung and breast cancer cells. To determine in vivo antitumor activity,
      nude mice bearing the cervical CaSki tumor xenograft were treated with ExoCUR by
      oral gavage, curcumin diet, exosomes alone, and PBS as controls. While curcumin
      via dietary route failed to elicit any effect, exosomes had a modest (25-30%)
      tumor growth inhibition. However, ExoCUR showed significant inhibition (61%; p <
      0.01) of the cervical tumor xenograft. No gross or systemic toxicity was observed
      in the rats administered with the exosomes or ExoCUR. These results suggest that
      exosomes can be developed as potential nano carriers for delivering curcumin
      which otherwise has encountered significant tissue bioavailability issues in the
      past.

PMID- 29047046
TI  - Letter to the Editor: Bariatric Surgery and Endoluminal Procedures: IFSO
      Worldwide Survey 2014.

PMID- 29047045
TI  - How sublexical association strength modulates updating: Cognitive and strategic
      effects.
AB  - In the current study, we investigated updating of long-term memory (LTM)
      associations. Specifically, we examined sublexical associations by manipulating
      preexisting LTM relations between consonant couplets (in encoding and updating
      phases), and explicitly instructed participants to engage with a specific
      strategy for approaching the task (item disjunction, grouping, or none). In two
      experiments, we used a multistep subject-based memory updating task in which we
      measured processing response times (RTs; Exp. 1, Exp. 2) and recognition RTs
      (Exp. 2). For the first time, in both experiments, we found costs in dismantling
      strong pre-existing associations from LTM and benefits in recreating strong
      preexisting associations. In addition, we found that control of irrelevant
      information was more difficult when this belonged to a strong association.
      Regarding task strategies, we showed that inducing a disjunction strategy
      enhanced updating, no matter the strength of the association. Results were
      discussed in the light of updating as a process of dismantling and recreating
      associations. The role of a specific strategic approach in enhancing the updating
      was also discussed.

PMID- 29047048
TI  - Correction to: Omeprazole Absorption and Fasting Gastrinemia After Roux-en-Y
      Gastric Bypass.
AB  - Larissa Alves dos Reis Dias wasmistakenly included in the 13 acknowledgment
      section of this article, and was mistakenly.

PMID- 29047047
TI  - Impact of Bariatric Surgery on Outcomes of Patients with Inflammatory Bowel
      Disease: a Nationwide Inpatient Sample Analysis, 2004-2014.
AB  - PURPOSE: There is a paucity of data regarding the benefits of bariatric surgery
      in patients with inflammatory bowel disease (IBD). The primary aim of this study
      was to evaluate the role of bariatric surgery on clinical outcomes among
      hospitalized patients with IBD. MATERIALS AND METHODS: The United States (US)
      National Inpatient Sample database was queried between 2004 and 2014 for
      discharges with co-diagnoses of morbid obesity and IBD. Hospitalizations with a
      history of prior-bariatric surgery were also identified. The primary outcome was
      in-hospital mortality. Secondary outcomes included renal failure, under
      nutrition, thromboembolic events, strictures, fistulae, length of stay, and
      hospitalization costs. Using Poisson regression, adjusted incidence risk ratios
      (IRR) were derived for clinical outcomes in patients with prior-bariatric surgery
      compared to those without bariatric surgery. RESULTS: Among 15,319 patients with
      a discharge diagnosis of IBD and morbid obesity, 493 patients (3.2%) had
      bariatric surgery. From 2004 to 2014, the proportion of obese IBD patients that
      underwent bariatric surgery declined (5.2 versus 3.1%). In a multivariable
      analysis, prior-bariatric surgery was associated with decreased IRR for renal
      failure, under-nutrition, and fistulae formation in morbidly obese IBD patients
      [(IRR 0.1; 95% CI 0.02-0.3; P < 0.001), (IRR 0.2; 95% CI 0.05-0.8; P = 0.03), and
      (IRR 0.1; 95% 0.2-08; P = 0.03), respectively]. Bariatric surgery did not
      influence mortality (P = 0.99). CONCLUSIONS: Despite a gradual increase in morbid
      obesity among patients with IBD, there has been a decrease in proportion of
      overall bariatric surgeries. Bariatric surgery appears to reduce morbidity in
      obese patients with IBD.

PMID- 29047049
TI  - Comparison of Imaging Modalities for Detecting Complications in Bariatric
      Surgery.
AB  - PURPOSE: The purpose of this study is to evaluate the results of routine
      fluoroscopic swallowing study (FSS) imaging 24 h after surgery and computed
      tomography (CT) on demand based on clinical data, in diagnosing complications
      after bariatric surgery. MATERIAL AND METHODS: This retrospective study includes
      9386 patients that underwent bariatric surgery. A total of 3241 (34.53%) patients
      underwent FSS imaging following the surgical procedure, and 106 (1.13%) patients
      underwent CT. RESULTS: Sleeve gastrectomy was performed in 8093 patients
      (75.81%), gastric bypass was performed in 1281 patients (12%), duodenal switch or
      biliopancreatic diversion was performed in 12 patients (0.11%), and gastric
      banding was performed in 1289 patients (12.07%), which were excluded from the
      study as no imaging modality was used in any of these patients. The sensitivity
      for FSS was 71.43% and the specificity was 99.85%. An analysis of disease
      prevalence revealed a value of 0.43% with a positive predictive value of 66.67%.
      The sensitivity for CT was 71.42% and the specificity was 98%. A disease
      prevalence analysis revealed a value of 6.60% with a positive predictive value of
      83.33%. A comparison of the two modalities showed that FSS has higher specificity
      values (p < 0.02) and a higher accuracy (p < 0.0001) than CT. CONCLUSION: CT and
      FSS have a similar sensitivity for diagnosing complications after bariatric
      surgery. However, the specificity and accuracy of FSS are superior to that of CT.
      This study was approved by the instructional ethics committee (Helsinki board)
      and was registered on the National Institutes of Health ( ClinicalTrials.gov )
      web site with identifier NCT02813122.

PMID- 29047050
TI  - Pituitary plasmacytoma-a rare presentation of multiple myeloma.

PMID- 29047051
TI  - Time Inhomogeneous Mutation Models with Birth Date Dependence.
AB  - The classic Luria-Delbruck model for fluctuation analysis is extended to the case
      where the split instant distributions of cells are not i.i.d.: the lifetime of
      each cell is assumed to depend on its birth date. This model takes also into
      account cell deaths and non-exponentially distributed lifetimes. In particular,
      it is possible to consider subprobability distributions and to model non
      exponential growth. The extended model leads to a family of probability
      distributions which depend on the expected number of mutations, the death
      probability of mutant cells, and the split instant distributions of normal and
      mutant cells. This is deduced from the Bellman-Harris integral equation, written
      for the birth date inhomogeneous case. A new theorem of convergence for the final
      mutant counts is proved, using an analytic method. Particular examples like the
      Haldane model or the case where hazard functions of the split-instant
      distributions are proportional are studied. The Luria-Delbruck distribution with
      cell deaths is recovered. A computation algorithm for the probabilities is
      provided.

PMID- 29047052
TI  - Effects of Zinc Oxide Nanoparticles on Performance, Egg Quality, Tissue Zinc
      Content, Bone Parameters, and Antioxidative Status in Laying Hens.
AB  - The objective of this study was to observe the effects of dietary supplementation
      with zinc oxide nanoparticles (ZnO-NPs) on performance, egg quality, tissue Zn
      content, bone parameters, superoxide dismutase activity (SOD), and egg
      malondialdehyde (MDA) content in laying hens. A total of 288 laying hens at 64
      weeks of age were randomly assigned to 4 treatments, 6 replicates, with 12 birds
      each. Experimental diets included the based diet (without Zn supplementation),
      and basal diet supplemented with 40, 80, and 120 mg Zn/kg from ZnO-NPs. Feed
      intake and egg mass were significantly higher in the 40 and 80 ZnO-NPs groups
      than the other groups. The birds in the 80 ZnO-NPs group had significantly higher
      egg product than the 120 ZnO-NPs and control groups. Egg shell thickness and
      shell strength significantly increased in the 40 and 80 ZnO-NPs groups. Moreover,
      Haugh unit significantly improved in the groups supplemented with ZnO-NPs,
      compared to the control group. Bone-breaking strength was significantly greater
      in the 80 ZnO-NPs group than the 120 ZnO-NPs and control groups. Also, ash weight
      was significantly greater in the 40 and 80 ZnO-NPs groups than the control group.
      There were significant differences among the groups in the Zn content in plasma,
      tibia, liver, pancreas, and egg. Relative to the control group, ZnO-NPs
      supplementation significantly increased the activities of SOD in the liver,
      pancreas, and plasma. The MDA content in egg was significantly reduced in the
      groups supplemented with ZnO-NPs. In conclusion, this study demonstrates that ZnO
      NPs as dietary supplementation can improve the performance of laying hens, and
      levels of 40 to 80 ZnO-NPs are the optimal concentrations.

PMID- 29047053
TI  - Mild Zellweger syndrome due to a novel PEX6 mutation: correlation between
      clinical phenotype and in silico prediction of variant pathogenicity.
AB  - Zellweger syndrome (ZS) is a consequence of a peroxisome biogenesis disorder
      (PBD) caused by the presence of a pathogenic mutation in one of the 13 genes from
      the PEX family. ZS is a severe multisystem condition characterized by neonatal
      appearance of symptoms and a shorter life. Here, we report a case of ZS with a
      mild phenotype, due to a novel PEX6 gene mutation. The patient presented subtle
      craniofacial dysmorphic features and slightly slower psychomotor development. At
      the age of 2 years, he was diagnosed with adrenal insufficiency, hypoacusis, and
      general deterioration. Magnetic resonance imaging showed a symmetrical
      hyperintense signal in the frontal and parietal white matter. Biochemical tests
      showed elevated liver transaminases, elevated serum very long chain fatty acids,
      and phytanic acid. After the death of the child at the age of 6 years, molecular
      diagnostics were continued in order to provide genetic counseling for his
      parents. Next generation sequencing (NGS) analysis with the TruSight OneTM
      Sequencing Panel revealed a novel homozygous PEX6 p.Ala94Pro mutation. In silico
      prediction of variant severity suggested its possible benign effect. To conclude,
      in the milder phenotypes, adrenal insufficiency, hypoacusis, and leukodystrophy
      together seem to be pathognomonic for ZS.

PMID- 29047054
TI  - Residual degradation and toxicity of insecticides against Bactrocera oleae.
AB  - Field and lab trials took place in Crete (July to September 2016), concerning the
      residual degradation and toxicity of seven active ingredients applied as bait
      sprays against the olive fruit fly. Highest residues were recorded in olive
      leaves for dimethoate and phosmet (~ 60 mg/kg) immediately after application (day
      1+), while a threefold and fivefold reduction was observed 1 week later,
      respectively. Residues of pyrethroids were determined at lower levels (< 10
      mg/kg) but remained almost stable for a longer period of time. Finally,
      thiacloprid and spinosad residues were determined at 5.81 and 0.19 mg/kg
      respectively (day 1+), and rapidly decreased below the LOQ. Highest toxicity
      against the olive fruit fly was observed just right after the application of
      dimethoate (100%), a-cypermethrin (80%), and L-cyhalothrin (72.92%). Although the
      toxicity of dimethoate was significantly reduced 1 week after the application
      (80%) and then minimized, toxicity of pyrethroids remained almost stable (> 60%)
      for the first 2 weeks and then decreased to 30-40%, which remained stable up to
      the end of the study (8 weeks). Concerning phosmet, its toxicity ranged from 35
      to 56% for 3 weeks with no significant reduction, while spinosad presented a
      lower toxicity profile (50% only for 1 week). The benefits of these results in
      the knowledge of insecticide residues and their toxicity against olive fruit fly
      can be used for improving olive fruit fly control.

PMID- 29047055
TI  - Experimental investigations on a diesel engine operated with fuel blends derived
      from a mixture of Pakistani waste tyre oil and waste soybean oil biodiesel.
AB  - The waste tyre and waste cooking oils have a great potential to be used as
      alternative fuels for diesel engines. The aim of this study was to convert light
      fractions of pyrolysis oil derived from Pakistani waste vehicle tyres and waste
      soybean oil methyl esters into valuable fuel and to reduce waste disposal
      associated environmental problems. In this study, the waste tyre pyrolysis liquid
      (light fraction) was collected from commercial tyre pyrolysis plant and biodiesel
      was prepared from waste soybean oil. The fuel blends (FMWO10, FMWO20, FMWO30,
      FMWO40 and FMWO50) were prepared from a 30:70 mixture of waste tyre pyrolysis
      liquid and waste soybean oil methyl esters with different proportions of mineral
      diesel. The mixture was named as the fuel mixture of waste oils (FMWO). FT-IR
      analysis of the fuel mixture was carried out using ALPHA FT-IR spectrometer.
      Experimental investigations on a diesel engine were carried out with various FMWO
      blends. It was observed that the engine fuel consumption was marginally increased
      and brake thermal efficiency was marginally decreased with FMWO fuel blends.
      FMWO10 has shown lowest NOx emissions among all the fuel blends tested. In
      addition, HC, CO and smoke emissions were noticeably decreased by 3.1-15.6%, 16.5
      33.2%, and 1.8-4.5%, respectively, in comparison to diesel fuel, thereby
      qualifying the blends to be used as alternative fuel for diesel engines.

PMID- 29047057
TI  - Strategies of heavy metal uptake by three Armeria species growing on different
      geological substrates in Serbia.
AB  - This study surveyed three species of the genus Armeria Willd. from five
      ultramafic outcrops, two non-ultramafic (schist) soils, and one tailing heap of
      an abandoned iron-copper mine from Serbia. Similarities and differences among the
      three Armeria species growing on different geological substrates in the ability
      to control uptake and translocate nine metals were examined. Chemical
      characteristics of the soil and plant samples (concentrations of P2O5, K2O, Ca,
      Fe, Mn, Ni, Zn, Cu, Cr, Co, Cd, and Pb) are presented. In order to assess
      accumulative potential of these three Armeria species, biological concentration,
      accumulation, as well as translocation factors were used. Three investigated
      Armeria species growing on eight different localities showed large differences in
      heavy metal uptake, translocation, and accumulation. The differences were present
      among the plant samples of the same species and even more among three different
      Armeria species and were primarily the result of the different contents of
      available heavy metals in the investigated soils. Additionally, differences might
      be the consequence of diverse responses and possible presence of supplementary
      resistance mechanisms in the plants from the ultramafic soils. None of the three
      Armeria species showed shoot hyperaccumulative potential for any of the
      investigated heavy metals and they could be considered as root accumulators,
      considering their potential to accumulate medium to large amounts of Zn (BCF up
      to 134), Cr (BCF up to 148), and Cd (BCF up to 9) in their roots.

PMID- 29047056
TI  - Chemical elements as fingerprints of geographical origin in cultivars of Vitis
      vinifera L. raised on the same SO4 rootstock.
AB  - The uptake of major and trace elements in grapevine (Vitis vinifera L.) can be
      influenced by soil, climate, geographic origin, and rootstock type. Rootstocks
      were mainly selected to resist phylloxera and for specific tolerance to lime,
      mineral uptake, drought, and salinity. The relationship among concentrations of
      major, trace, and rare earth elements was studied in soil and leaves from two
      Italian grapevine cultivars, "Cabernet Sauvignon" and "Corvina," employed to
      produce renowned controlled designation of origin (DOC) wines. The cultivars were
      raised on the same rootstock SO4 in two different areas of the Veneto Region
      (Northern Italy). The elements were studied by X-ray fluorescence and inductively
      coupled plasma mass spectrometry, and data were elaborated by non-parametric
      tests and multivariate linear discrimination analysis. The related index of
      bioaccumulation was calculated to define the specific assimilation of the
      elements from soil to leaves. A statistically significant correspondence between
      soil and leaf samples was observed for Mg, Sm, V, and Zr. The results allowed to
      discriminate soil and leaf samples of the two cultivars according to geographical
      provenance, possibly providing geochemical markers (fingerprints) useful against
      fraudulent use of DOC wine labels.

PMID- 29047058
TI  - Lead in roadway dusts from different functional areas in a typical valley city,
      NW China: contamination and exposure risk.
AB  - Lead contamination and exposure risk assessment in roadway dusts from four
      different functional areas in a typical valley city in northwest China (Xi'an)
      were conducted in this study. A total of 130 roadway dust samples from park area
      (PA), traffic area (TA), educational area (EA), and residential area (RA) were
      collected and Pb concentrations in the samples were determined by using XRF (X
      ray fluorescence). Geo-accumulation index (I geo) and enrichment factor (EF) were
      applied to assess Pb contamination level and the hazard indexes (HI) of Pb were
      calculated to evaluate the exposure risks to children and adults. The results
      showed that roadway dusts from all four functional areas had elevated Pb
      concentrations and pollution characteristics of Pb were discrepant in different
      functional areas. The mean concentration of Pb in roadway dusts from PA, TA, EA,
      and RA was 147.4, 74.8, 119.6, and 161.0 mg kg-1, respectively. The I geo and EF
      of Pb were mostly 1-3 and 2-20, which indicated moderate to high Pb contamination
      in roadway dusts. High contamination level of Pb in RA and EA should receive
      priority for prevention and control. Exposure risk assessment of Pb from roadway
      dusts was mainly in the acceptable range, but the potential risk of Pb exposure
      to children should be continuously concerned.

PMID- 29047059
TI  - Characterization of carbonaceous fractions in PM2.5 and PM10 over a typical
      industrial city in central China.
AB  - Aerosol samples of PM2.5 and PM10 were collected every 6 days from March 2012 to
      February 2013 in Huangshi, a typical industrial city in central China, to
      investigate the characteristics, relationships, and sources of carbonaceous
      species. The PM2.5 and PM10 samples were analyzed for organic carbon (OC),
      elemental carbon (EC), char, and soot using the thermal/optical reflectance (TOR)
      method following the IMPROVE_A protocol. PM2.5 and PM10 concentrations ranged
      from 29.37 to 501.43 MUg m-3 and from 50.42 to 330.07 MUg m-3, with average
      levels of 104.90 and 151.23 MUg m-3, respectively. The 24-h average level of
      PM2.5 was about three times the US EPA standard of 35 MUg m-3, and significantly
      exceeds the Class II National Air Quality Standard of China of 75 MUg m-3. The
      seasonal cycles of PM mass and OC concentrations were higher during winter than
      in summer. EC and char concentrations were generally highest during winter but
      lowest in spring, while higher soot concentrations occurred in summer. This
      seasonal variation could be attributed to different seasonal meteorological
      conditions and changes in source contributions. Strong correlations between OC
      and EC were found for both PM2.5 and PM10 in winter and fall, while char and soot
      showed a moderate correlation in summer and winter. The average OC/EC ratios were
      5.11 and 4.46 for PM2.5 and PM10, respectively, with individual OC/EC ratios
      nearly always exceeding 2.0. Higher char/soot ratios during the four seasons
      indicated that coal combustion and biomass burning were the major sources for
      carbonaceous aerosol in Huangshi. Contrary to expectations, secondary organic
      carbon (SOC) which is estimated using the EC tracer method exhibited spring
      maximum and summer minimum, suggesting that photochemical activity is not a
      leading factor in the formation of secondary organic aerosols in the study area.
      The contribution of SOC to OC concentration for PM2.5 and PM10 were 47.33 and
      45.38%, respectively, implying that SOC was an important component of OC mass.
      The serious air pollution in haze-fog episode was strongly correlated with the
      emissions of pollutants from biomass burning and the meteorological conditions.

PMID- 29047060
TI  - Association between coal consumption and urbanization in a coal-based region: a
      multivariate path analysis.
AB  - This study examines causal relationship between urbanization and coal
      consumption. By taking Shanxi Province, China, as a typical case area, a
      multivariate path analysis model is used to seek for the key driving factors of
      coal consumption throughout its urbanization during the period of 1978 to 2014.
      The result indicates that the key factors are urban household disposable income
      and residential area per capita, which are closely related to urban construction
      and household lifestyle. It is expected that the study may inform better policies
      on coal consumption reduction and energy structure improvement.

PMID- 29047061
TI  - Release and kinetics of arsenic and plumbum in the Songhua River surficial
      sediments.
AB  - To estimate the pollution of As and Pb in the Songhua River which flows through
      the major rice-producing regions in China, the present study investigated the
      level and release of As and Pb in surficial sediments which collected from nine
      sites in Songhua River (M1-M9). The concentration of As and Pb was ranged as
      follows: As = 3.104~15.01 MUg/g, Pb = 20.10~37.42 MUg/g; the average
      concentration: As = 6.466 +/- 3.077 MUg/g, Pb = 28.88 +/- 5.077 MUg/g. By
      analysis vertically, the average concentration of As was 5.166 +/- 1.496 MUg/g in
      the upstream, 5.815 +/- 1.793 MUg/g in the midstream, and 9.716 +/- 4.977 MUg/g
      in the downstream. The average concentration of Pb was 27.83 +/- 4.552 MUg/g in
      the upstream, 28.66 +/- 6.333 MUg/g in the midstream, and 30.99 +/- 4.837 MUg/g
      in the downstream. It indicated that the concentration of As and Pb increased
      gradually from upstream to downstream. As existed mainly as insoluble state and
      Pb existed mainly as sulfide and organic combining state in surficial sediments,
      and the species of As and Pb could transform with the change of the circumstance.
      The release of quantity of As was higher than Pb. The pH of 6 was not conducive
      to the release of As and Pb. When the temperature was 35 and 6  degrees C, the
      release of As and Pb in surficial sediments were restrained, respectively.
      Fumaric acid and citric acid played an important role in promoting the release of
      As, but not conducive to Pb. Furthermore, the reasonable aeration rate was
      beneficial to the release process of As and Pb in surficial sediment. By kinetic
      analysis, the Elovich equation (Ct = 84.931-8.952lnt) could be used to describe
      the dynamic process of the release of As in a relatively short time. The Elovich
      equation (C t  = 2.724 + 1.3724lnt) and double constant rate equation (lnC T  =
      1.4646 + 0.1522lnT) could well describe the dynamics process of the release of
      Pb.

PMID- 29047062
TI  - Fungicidal activity of slow-release P(3HB)/TEB formulations in wheat plant
      communities infected by Fusarium moniliforme.
AB  - Fungicidal activity of experimental tebuconazole (TEB) formulations was
      investigated in laboratory soil ecosystems in wheat plant communities infected by
      Fusarium moniliforme. TEB was embedded in the matrix of poly-3-hydroxybutyrate,
      shaped as films and microgranules. These formulations were buried in the soil
      with wheat plants, and their efficacy was compared with that of commercial
      formulation Raxil and with the effect of pre-sowing treatment of seeds. In the
      experiment with the initially infected seeds and a relatively low level of
      natural soil infection caused by Fusarium fungi, the effects of the experimental
      P(3HB)/TEB formulations and Raxil were comparable. However, when the level of
      soil infection was increased by adding F. moniliforme spores, P(3HB)/TEB granules
      and films reduced the total counts of fungi and the abundance of F. moniliforme
      more effectively than Raxil. Seed treatment or soil treatment with Raxil solution
      showed an increase in the percentage of rot-damaged roots in the later stages of
      the experiment. In the early stage (between days 10 and 20), the percentage of
      rot-damaged roots in the soil with TEB embedded in the slowly degraded P(3HB)
      matrix was similar to that in the soil with Raxil. However, the efficacy of
      P(3HB)/TEB formulations lasted longer, and in later stages (between days 20 and
      30), the percentage of rot-damaged roots in that group did not grow. In
      experiments with different TEB formulations and, hence, different fungicidal
      activities, the increase in plant biomass was 15-17 to 40-60% higher than in the
      groups where TEB was applied by using conventional techniques.

PMID- 29047063
TI  - Life-cycle impacts of shower water waste heat recovery: case study of an
      installation at a university sport facility in the UK.
AB  - Recovering heat from waste water discharged from showers to preheat the incoming
      cold water has been promoted as a cost-effective, energy-efficient, and low
      carbon design option which has been included in the UK's Standard Assessment
      Procedure (SAP) for demonstrating compliance with the Building Regulation for
      dwellings. Incentivized by its carbon cost-effectiveness, waste water heat
      exchangers (WWHX) have been selected and incorporated in a newly constructed
      Sports Pavilion at the University of Brighton in the UK. This L2-m sports
      development serving several football fields was completed in August 2015
      providing eight water- and energy-efficient shower rooms for students, staff, and
      external organizations. Six of the shower rooms are located on the ground floor
      and two on the first floor, each fitted with five or six thermostatically
      controlled shower units. Inline type of WWHX were installed, each consisted of a
      copper pipe section wound by an external coil of smaller copper pipe through
      which the cold water would be warmed before entering the shower mixers. Using the
      installation at Sport Pavilion as the case study, this research aims to evaluate
      the environmental and financial sustainability of a vertical waste heat recovery
      device, over a life cycle of 50 years, with comparison to the normal use of a PVC
      u pipe. A heat transfer mathematical model representing the system has been
      developed to inform the development of the methodology for measuring the in-situ
      thermal performance of individual and multiple use of showers in each changing
      room. Adopting a system thinking modeling technique, a quasi-dynamic simulation
      computer model was established enabling the prediction of annual energy
      consumptions under different shower usage profiles. Data based on the process map
      and inventory of a functional unit of WWHX were applied to a proprietary
      assessment software to establish the relevant outputs for the life-cycle
      environmental impact assessment. Life-cycle cost models were developed and
      industry price book data were applied. The results indicated that the seasonal
      thermal effectiveness was over 50% enabling significant energy savings through
      heat recovery that led to short carbon payback time of less than 2 years to
      compensate for the additional greenhouse gas emissions associated with the WWHX.
      However, the life-cycle cost of the WWHX is much higher than using the PVC pipe,
      even with significant heat recovered under heavy usage, highlighting the need to
      adopt more economic configurations, such as combining waste water through fewer
      units, in order to maximize the return on investment and improve the financial
      viability.

PMID- 29047064
TI  - Are distinct nitrous oxide emission factors required for cattle urine and dung
      deposited on pasture in western Canada?
AB  - While some countries disaggregate N2O emission factors for urine and dung
      deposited onto pastures, in Canada, distinct N2O emission factors for beef cattle
      urine and dung have not been defined. To help address this knowledge gap, we
      conducted a 1-year study to quantify N2O fluxes from beef cattle urine and dung
      patches on a semiarid tame pasture in western Canada, as well as to quantify the
      N2O emission factors (EF3) for urine and dung as the percentage of applied N
      emitted as N2O-N. Urine and dung were deposited when soil water-filled pore space
      was nearly 60%, a wet soil condition for the grazing season in the semiarid study
      region, which led to a burst of N2O from urine in the first 14 days of the study
      (42% of total N emitted). Urine emitted more cumulative N2O (P < 0.001) and had a
      greater N2O emission factor (P = 0.002) than dung. The urine patch emitted 1.30
      +/- 0.47 g N2O-N m-2 year-1, while the dung patch emitted 0.083 +/- 0.020 g N2O-N
      m-2 year-1 (mean values +/- SD). The N2O emission factor for urine was 1.32 +/-
      0.49%, while for dung it was 0.03 +/- 0.02%. We conclude that more study is
      needed to determine if distinct N2O emission factors are required for urine and
      dung deposited onto pasture in western Canada to more accurately estimate
      national N2O inventories.

PMID- 29047065
TI  - First determination of fullerenes in the Austrian market and environment:
      quantitative analysis and assessment.
AB  - This study forms the first report on analyzing fullerenes in the Austrian
      environment and cosmetic products available on the Austrian market. We developed,
      optimized, and validated a novel method for the analysis of C60 and C70
      fullerenes and N-methylfulleropyrrolidine C60 (NMFP) for measuring sensitivities
      in the low nanograms per liter range in order to prove their presence in the
      environment (12 wastewater- and 12 sewage sludge samples) and in 11 selected
      fullerene-containing cosmetic products from three different brands. The optimized
      method relies on a liquid-liquid extraction (LLE) or solid-liquid extraction
      (SLE) and, for the first time, introduced the Carrez-clarification, followed by
      liquid chromatography (LC) and coupled to a hybrid triple quadrupole mass
      spectrometry (MS) quantification. The total variability of the new established LC
      MS/MS method based on all the tested matrices was below 10%. We found recoveries
      generally higher than 70% for both tap water and surface water. The limits of
      quantitation (LOQ) for the wastewater samples were measured to be from 0.8 to 1.6
      ng/L, for the sewage sludge samples, from 1.4 to 2.6 ng/g DM (drymass), and for
      the cosmetic samples from 0.2 to 0.4 ng/g. None of the analyzed samples of
      wastewater or sewage sludge samples contained fullerenes. But in 70% of the
      tested cosmetics, fullerene concentrations between 10 and 340 ng/g were detected.
      These values were much lower than concentrations causing toxicity in water
      animals.

PMID- 29047066
TI  - Spatial distribution and potential biological risk of some metals in relation to
      granulometric content in core sediments from Chilika Lake, India.
AB  - The article presents first systematic report on the concentration of selected
      major elements [iron (Fe) and manganese (Mn)] and minor elements [zinc (Zn),
      copper (Cu), chromium (Cr), lead (Pb), nickel (Ni), and cobalt (Co)] from the
      core sediment of Chilika Lake, India. The analyzed samples revealed higher
      content of Pb than the background levels in the entire study area. The extent of
      contamination from minor and major elements is expressed by assessing (i) the
      metal enrichments in the sediment through the calculations of anthropogenic
      factor (AF), pollution load index (PLI), Enrichment factor (EF), and
      geoaccumulation index (Igeo) and (ii) potential biological risks by the use of
      sediment quality guidelines like effect range median (ERM) and effect range low
      (ERL) benchmarks. The estimated indices indicated that sediment is enriched with
      Pb, Ni, Cr, Cu and Co. The enrichment of these elements seems to be due to the
      fine granulometric characteristics of the sediment with Fe and Mn oxyhydroxides
      being the main metal carriers and fishing boats using low grade paints, fuel, and
      fishing technology using lead beads fixed to fishing nets. Trace element input to
      the Chilika lake needs to be monitored with due emphasis on Cr and Pb
      contaminations since the ERM and ERL benchmarks indicated potential biological
      risk with these metals.

PMID- 29047067
TI  - Spatial distributions, fractionation characteristics, and ecological risk
      assessment of trace elements in sediments of Chaohu Lake, a large eutrophic
      freshwater lake in eastern China.
AB  - The concentrations, spatial distribution, fractionation characteristics, and
      potential ecological risks of trace elements (Cu, Pb, Zn, Cr, Ni, and Co) in the
      surface sediment samples collected from 32 sites in Chaohu Lake were
      investigated. The improved BCR sequential extraction procedure was applied to
      analyze the chemical forms of trace elements in sediments. The enrichment factor
      (EF), sediment quality guidelines (SQGs), potential ecological risk index (PERI),
      and risk assessment code (RAC) were employed to evaluate the pollution levels and
      the potential ecological risks. The results found that the concentrations of Cu,
      Pb, Zn, Cr, Ni, and Co in the surface sediments were 78.59, 36.91, 161.84, 98.87,
      38.92, and 10.09 mg kg-1, respectively. The lower concentrations of Cu, Pb, Zn,
      Cr, and Ni were almost found in the middle part of the lake, while Co increased
      from the western toward the eastern parts of the lake. Cr, Ni, Co, and Zn
      predominantly existed in the residual fractions, with the average values of
      76.35, 59.22, 45.60, and 44.30%, respectively. Cu and Pb were mainly combined
      with Fe/Mn oxides in reducible fraction, with the average values of 66.4 and
      69.1%, respectively. The pollution levels were different among the selected
      elements. Cu had the highest potential ecological risk, while Cr had the lowest
      potential ecological risk.

PMID- 29047068
TI  - Intraductal Papillary Mucinous Neoplasm of the Pancreas in Young Patients: Tumor
      Biology, Clinical Features, and Survival Outcomes.
AB  - AIM: The aim of this paper is to describe the characteristics of intraductal
      papillary mucinous neoplasms (IPMNs) of the pancreas in young patients. METHODS:
      We evaluated 1693 patients from the Pancreatic Surgery Consortium who underwent
      resection for IPMN and classified them as younger or older than 50 years of age
      at the time of surgery. We assessed the relationship of age with clinical,
      radiological, pathological, and prognostic features. RESULTS: We identified 90
      (5%) young patients. Age was not associated with differences in main pancreatic
      duct size (P = 0.323), presence of solid components (P = 0.805), or cyst size (P
      = 0.135). IPMNs from young patients were less likely to be of gastric type (37
      vs. 57%, P = 0.005), and more likely to be of oncocytic (15 vs. 4%, P = 0.003)
      and intestinal types (44 vs. 26%, P = 0.004). Invasive carcinomas arising from
      IPMN were less common in young patients (17 vs. 27%, P = 0.044), and when present
      they were commonly of colloid type (47 vs. 31% in older patients, P = 0.261) and
      had better overall survival than older patients (5-year, 71 vs. 37%, log-rank P =
      0.031). CONCLUSION: Resection for IPMN is infrequent in young patients, but when
      they are resected, IPMNs from young patients demonstrate different epithelial
      subtypes from those in older patients and more favorable prognosis.

PMID- 29047069
TI  - Postoperative Visceral Tissue Edema Assessed by Computed Tomography Is a
      Predictor for Severe Complications After Pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: In pancreatoduodenectomy (PD), the adverse impact of tissue
      edema owing to intraoperative fluid overload remains unclear. This study aims to
      evaluate how visceral tissue edema due to fluid overload affects severe
      postoperative complications after PD. It aims to clarify the usefulness of
      assessment by computed tomography (CT) of postoperative tissue edema. METHODS: We
      classified 200 patients who underwent PD as either liberal fluid management (LFM)
      group (n = 100) or goal-directed fluid therapy (GDFT) group (n = 100), based on
      intraoperative fluid management. We assessed postoperative tissue edema by cross
      section of the body trunk area using pre- and postoperative CT. RESULTS: Severe
      complication (Clavien-Dindo more than grade III) rate was significantly higher in
      LFM group than GDFT group (37 vs. 17%, P = 0.001). Independent risk factors of
      severe complications after PD included diameter of main pancreatic duct <= 3 mm
      at the cut surface (P = 0.041; OR 2.274; 95% CI 1.034-5.001), LFM (P = 0.005; OR
      2.720; 95% CI 1.355-5.462), and increased rate of body trunk area >= 20% (P <
      0.001; OR 3.448; 95% CI 1.723-5.462). In subgroup analysis of patients with no
      transfusion, LFM and increased rate of body trunk area >= 20% were independent
      risk factors of severe postoperative complications. CONCLUSIONS: Visceral tissue
      edema evaluation is a valuable method to predict severe complications after PD.

PMID- 29047070
TI  - Predictive Factors for Lymph Node Metastasis and Prognostic Factors for Survival
      in Rectal Neuroendocrine Tumors.
AB  - INTRODUCTION: Neuroendocrine tumors have malignant potential, and lymph node
      metastasis can occur. This study aimed to identify predictive factors of lymph
      node metastasis and prognostic factors for survival in rectal neuroendocrine
      tumors. METHODS: Sixty-four patients underwent endoscopic or surgical treatment
      for rectal NET. The data on these patients were collected in our database
      prospectively and reviewed retrospectively. RESULTS: Transanal excision was
      performed in 28 (43.8%) patients, endoscopic mucosal resection or submucosal
      dissection was performed in 15 (23.4%) patients, and radical resection was
      performed in 21 (31.8%) patients. Lymph node and distant metastasis was present
      in 16 (25.0%) and fir (7.8%) patients. The significant risk factors for lymph
      node metastasis identified in the multivariable analyses were tumor size (>= 2
      cm, p = 0.003) and tumor grade (G2, p < 0.001; G3, p = 0.008). In patients with a
      tumor smaller than 2 cm, the risk factors for lymph node metastasis included the
      tumor grade, mitosis count, and Ki-67 index. The median follow-up period was 30.0
      months, and recurrence developed in four (6.8%) patients. The significant
      prognostic factors for survival included tumor size, T stage, lymph node
      metastasis, and tumor grade. CONCLUSION: Tumor grade combined with tumor size is
      an important predictive factor for lymph node metastasis and could serve as a
      prognostic factor for survival outcomes.

PMID- 29047071
TI  - Category effects on stimulus estimation: Shifting and skewed frequency
      distributions-A reexamination.
AB  - Duffy, Huttenlocher, Hedges, and Crawford (Psychonomic Bulletin & Review, 17(2),
      224-230, 2010) report on experiments where participants estimate the lengths of
      lines. These studies were designed to test the category adjustment model (CAM), a
      Bayesian model of judgments. The authors report that their analysis provides
      evidence consistent with CAM: that there is a bias toward the running mean and
      not recent stimuli. We reexamine their data. First, we attempt to replicate their
      analysis, and we obtain different results. Second, we conduct a different
      statistical analysis. We find significant recency effects, and we identify
      several specifications where the running mean is not significantly related to
      judgment. Third, we conduct tests of auxiliary predictions of CAM. We do not find
      evidence that the bias toward the mean increases with exposure to the
      distribution. We also do not find that responses longer than the maximum of the
      distribution or shorter than the minimum become less likely with greater exposure
      to the distribution. Fourth, we produce a simulated dataset that is consistent
      with key features of CAM, and our methods correctly identify it as consistent
      with CAM. We conclude that the Duffy et al. (2010) dataset is not consistent with
      CAM. We also discuss how conventions in psychology do not sufficiently reduce the
      likelihood of these mistakes in future research. We hope that the methods that we
      employ will be used to evaluate other datasets.

PMID- 29047072
TI  - Involving Members of the Public in Health Economics Research: Insights from
      Selecting Health States for Valuation to Estimate Quality-Adjusted Life-Year
      (QALY) Weights.
AB  - Over recent years, public involvement in health research has expanded
      considerably. However, public involvement in designing and conducting health
      economics research is seldom reported. Here we describe the development, delivery
      and assessment of an approach for involving people in a clearly defined piece of
      health economics research: selecting health states for valuation in estimating
      quality-adjusted life-years (QALYs). This involvement formed part of a study to
      develop a condition-specific preference-based measure of health-related quality
      of life, the Multiple Sclerosis Impact Scale (MSIS-8D), and the work reported
      here relates to the identification of plausible, or realistic, health states for
      valuation. An Expert Panel of three people with multiple sclerosis (MS) was
      recruited from a local involvement network, and two health economists designed an
      interactive task that enabled the Panel to identify health states that were
      implausible, or unlikely to be experienced. Following some initial confusion over
      terminology, which was resolved by discussion with the Panel, the task worked
      well and can be adapted to select health states for valuation in the development
      of any preference-based measure. As part of the involvement process, five themes
      were identified by the Panel members and the researchers which summarised our
      experiences of public involvement in this health economics research example:
      proportionality, task design, prior involvement, protectiveness and partnerships.
      These are described in the paper, along with their practical implications for
      involving members of the public in health economics research. Our experience
      demonstrates how members of the public and health economists can work together to
      improve the validity of health economics research. Plain Language Summary It has
      become commonplace to involve members of the public in health service research.
      However, published reports of involving people in designing health economics
      research are rare. We describe how we designed a way of involving people in a
      particular piece of health economics research.The aim of the work was to produce
      descriptions of different states of health experienced by people with multiple
      sclerosis (MS). These descriptions have since been rated in terms of how good or
      bad they are in a way that can be used by the National Institute for Health and
      Care Excellence (NICE) to make decisions about what services to fund on the
      NHS.We formed a panel of three people with MS, and designed a task to help the
      group produce health descriptions likely to be experienced by people with MS.
      After discussion about jargon, and working together to find more layman's terms,
      the task worked well, and can be adapted to produce health descriptions for any
      condition.We identified some key themes about working together that give insights
      into how members of the public can be involved in health economics research, and
      show the importance of their involvement in improving the relevance of this
      research.

PMID- 29047073
TI  - Rounds with Dr. Seuss: Formulating a Case of Takotsubo Syndrome through Theodor
      Seuss Geisel's How the Grinch Stole Christmas.

PMID- 29047074
TI  - Clinical Informatics in Psychiatric Training: Preparing Today's Trainees for the
      Already Present Future.

PMID- 29047075
TI  - Body Image, Media, and Eating Disorders-a 10-Year Update.

PMID- 29047076
TI  - Increased Rates of Documented Alcohol Counseling in Primary Care: More Counseling
      or Just More Documentation?
AB  - BACKGROUND: Clinical performance measures often require documentation of patient
      counseling by healthcare providers. Little is known about whether such measures
      encourage delivery of counseling or merely its documentation. OBJECTIVE: To
      assess changes in provider documentation of alcohol counseling and patient report
      of receiving alcohol counseling in the Veterans Administration (VA) from 2009 to
      2012. DESIGN: Retrospective time-series analysis. PARTICIPANTS: A total of 5413
      men who screened positive for unhealthy alcohol use at an outpatient visit and
      responded to a confidential mailed survey regarding alcohol counseling from a VA
      provider in the prior year. MAIN MEASURES: Rates of provider documentation of
      alcohol counseling in the electronic health record and patient report of such
      counseling on the survey were assessed over 4 fiscal years. Annual rates were
      calculated overall and with patients categorized into four mutually exclusive
      groups based on their own reports of alcohol counseling (yes/no) and whether
      alcohol counseling was documented by a provider (yes/no). KEY RESULTS: Provider
      documentation of alcohol counseling increased 23.6% (95% CI: 17.0, 30.2), from
      59.4% to 83.0%, while patient report of alcohol counseling showed no significant
      change (4.0%, 95% CI: -2.3, 10.3), increasing from 66.1% to 70.1%. An 18.7% (95%
      CI: 11.7, 25.7) increase in the proportion of patients who reported counseling
      that was documented by a provider largely reflected a 14.7% decline (95% CI: 8.5,
      20.8) in the proportion of patients who reported alcohol counseling that was not
      documented by a provider. The proportion of patients who did not report
      counseling but whose providers documented it did not show a significant change
      (4.9%, 95%CI: 0.0, 9.9). CONCLUSIONS: If patient report is accurate, increased
      rates of documented alcohol counseling in the VA from 2009 to 2012 predominantly
      reflected improved documentation of previously undocumented counseling rather
      than delivery of additional counseling or increased documentation of counseling
      that did not meaningfully occur.

PMID- 29047077
TI  - Adventitial Fibroblast Nox4 Expression and ROS Signaling in Pulmonary Arterial
      Hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease arising from
      remodeling and narrowing of pulmonary arteries (PA) resulting in high pulmonary
      arterial blood pressure and ultimately right ventricular failure. Elevated
      production of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4), a
      constitutively active enzyme, has been associated with oxygen sensing, vasomotor
      control, cellular proliferation, differentiation, migration, apoptosis,
      senescence, fibrosis, and angiogenesis. Further, elevated expression of Nox4 has
      been reported in a number of cardiovascular diseases, including atherosclerosis,
      hypertension, cardiac failure, ischemic stroke, and PAH. However, the cellular
      location of Nox4 and its contribution to aberrant vascular remodeling in PAH
      remains poorly understood. The goal of this review is to summarize the recent
      literature on the enzymatic regulation of Nox4 in the production of ROS in PAH.
      In the vascular wall, Nox4 is present in fibroblasts, a primary cell of the
      adventitia, and matches the adventitial location of ROS production in PAH.
      Further, in adventitial fibroblasts, Nox4 overexpression stimulates migration and
      proliferation as well as matrix gene expression. Collectively, reports indicate
      that Nox4 contributes to altered fibroblast behavior, ROS production leading to
      hypertensive vascular remodeling and the development of PAH. Finally, we address
      the functional significance of Nox4 in fibroblasts, and also suggest an "outside
      in" (adventitial) process of vascular remodeling that is mediated by Nox4, which
      although has physiological roles in the intimal layer (i.e., endothelium), may
      also have pathologic importance in the adventitial layer of the vascular wall
      through signaling in fibroblasts.

PMID- 29047078
TI  - Role of Transcription Factors in Pulmonary Artery Smooth Muscle Cells: An
      Important Link to Hypoxic Pulmonary Hypertension.
AB  - Hypoxia, namely a lack of oxygen in the blood, induces pulmonary vasoconstriction
      and vasoremodeling, which serve as essential pathologic factors leading to
      pulmonary hypertension (PH). The underlying molecular mechanisms are uncertain;
      however, pulmonary artery smooth muscle cells (PASMCs) play an essential role in
      hypoxia-induced pulmonary vasoconstriction, vasoremodeling, and PH. Hypoxia
      causes oxidative damage to DNAs, proteins, and lipids. This damage (oxidative
      stress) modulates the activity of ion channels and elevates the intracellular
      calcium concentration ([Ca2+]i, Ca2+ signaling) of PASMCs. The oxidative stress
      and increased Ca2+ signaling mutually interact with each other, and
      synergistically results in a variety of cellular responses. These responses
      include functional and structural abnormalities of mitochondria, sarcoplasmic
      reticulum, and nucleus; cell contraction, proliferation, migration, and
      apoptosis, as well as generation of vasoactive substances, inflammatory
      molecules, and growth factors that mediate the development of PH. A number of
      studies reveal that various transcription factors (TFs) play important roles in
      hypoxia-induced oxidative stress, disrupted PAMSC Ca2+ signaling and the
      development and progress of PH. It is believed that in the pathogenesis of PH,
      hypoxia facilitates these roles by mediating the expression of multiple genes.
      Therefore, the identification of specific genes and their transcription factors
      implicated in PH is necessary for the complete understanding of the underlying
      molecular mechanisms. Moreover, this identification may aid in the development of
      novel and effective therapeutic strategies for PH.

PMID- 29047079
TI  - Molecular Basis of Nitrative Stress in the Pathogenesis of Pulmonary
      Hypertension.
AB  - Pulmonary hypertension (PH) is a lung vascular disease with marked increases in
      pulmonary vascular resistance and pulmonary artery pressure (>25 mmHg at rest).
      In PH patients, increases in pulmonary vascular resistance lead to impaired
      cardiac output and reduced exercise tolerance. If untreated, PH progresses to
      right heart failure and premature lethality. The mechanisms that control the
      pathogenesis of PH are incompletely understood, but evidence from human and
      animal studies implicate nitrative stress in the development of PH. Increased
      levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS)
      result in nitrative stress, which in turn induces posttranslational modification
      of key proteins important for maintaining pulmonary vascular homeostasis. This
      affects their functions and thereby contributes to the pathogenesis of PH. In
      this chapter, molecular mechanisms underlying nitrative stress-induced PH are
      reviewed, molecular sources of ROS and RNS are delineated, and evidence of
      nitrative stress in PH patients is described. A better understanding of such
      mechanisms could lead to the development of novel treatments for PH.

PMID- 29047080
TI  - Pentose Shunt, Glucose-6-Phosphate Dehydrogenase, NADPH Redox, and Stem Cells in
      Pulmonary Hypertension.
AB  - Redox signaling plays a critical role in the pathophysiology of cardiovascular
      diseases. The pentose phosphate pathway is a major source of NADPH redox in the
      cell. The activities of glucose-6-phosphate dehydrogenase (the rate-limiting
      enzyme in the pentose shunt) and glucose flux through the shunt pathway is
      increased in various lung cells including, the stem cells, in pulmonary
      hypertension. This chapter discusses the importance of the shunt pathway and
      glucose-6-phosphate dehydrogenase in the pathogenesis of pulmonary artery
      remodeling and occlusive lesion formation within the hypertensive lungs.

PMID- 29047081
TI  - Redox Regulation of the Superoxide Dismutases SOD3 and SOD2 in the Pulmonary
      Circulation.
AB  - When evaluating the role of redox-regulating signaling in pulmonary vascular
      diseases, it is intriguing to consider the modulation of key antioxidant enzymes
      like superoxide dismutase (SOD) because SOD isoforms are regulated by redox
      reactions, and, in turn, modulate downstream redox sensitive processes. The
      emerging field of redox biology is built upon understanding the regulation and
      consequences of tightly controlled and specific reduction-oxidation reactions
      that are critical for diverse cellular processes including cell signaling. Of
      relevance, both the site of production of specific reactive oxygen and nitrogen
      species and the site of the antioxidant defenses are highly compartmentalized
      within the cell. For example, superoxide is generated during oxidative
      phosphorylation in the mitochondria as well as by a number of enzymatic sources
      within the cytosol and at the cell membrane. In the pulmonary circulation, these
      sources include the mitochondrial electron transport chain, NADPH oxidases (NOX1
      4, Duox1,2), nitric oxide synthases, and xanthine oxidase; this important topic
      has been thoroughly reviewed recently [1]. In parallel with these different
      cellular sites of superoxide production, the three SOD isoforms are also
      specifically localized to the cytosol (SOD1), mitochondria (SOD2) or
      extracellular compartment (SOD3). This chapter focuses on the role of redox
      mechanisms regulating SOD2 and SOD3, with an emphasis on these processes in the
      setting of pulmonary hypertension.

PMID- 29047083
TI  - Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary
      Hypertension.
AB  - Normally, the pulmonary circulation is maintained in a low-pressure, low
      resistance state with little resting tone. Pulmonary arteries are thin-walled and
      rely heavily on pulmonary arterial distension and recruitment for reducing
      pulmonary vascular resistance when cardiac output is elevated. Under
      pathophysiological conditions, however, active vasoconstriction and vascular
      remodeling lead to enhanced pulmonary vascular resistance and subsequent
      pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor
      associated with the development of PH resulting from airway obstruction (COPD,
      sleep apnea), diffusion impairment (interstitial lung disease), developmental
      lung abnormalities, or high altitude exposure (World Health Organization [WHO];
      Group III). The rise in pulmonary vascular resistance increases right heart
      afterload causing right ventricular hypertrophy that can ultimately lead to right
      heart failure in patients with chronic lung disease. PH is typically
      characterized by diminished paracrine release of vasodilators, antimitogenic
      factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and
      enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive
      oxygen species and endothelin-1) from the endothelium and lung parenchyma. In
      addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC),
      including alterations in Ca2+ homeostasis, Ca2+ sensitivity, and activation of
      transcription factors are thought to play prominent roles in the development of
      both vasoconstrictor and arterial remodeling components of hypoxia-associated PH.
      These changes in PASMC function are briefly reviewed in Sect. 1 and the influence
      of altered reactive oxygen species homeostasis on PASMC function discussed in
      Sects. 2-4.

PMID- 29047084
TI  - ROS Signaling in the Pathogenesis of Acute Lung Injury (ALI) and Acute
      Respiratory Distress Syndrome (ARDS).
AB  - The generation of reactive oxygen species (ROS) plays an important role for the
      maintenance of cellular processes and functions in the body. However, the
      excessive generation of oxygen radicals under pathological conditions such as
      acute lung injury (ALI) and its most severe form acute respiratory distress
      syndrome (ARDS) leads to increased endothelial permeability. Within this hallmark
      of ALI and ARDS, vascular microvessels lose their junctional integrity and show
      increased myosin contractions that promote the migration of polymorphonuclear
      leukocytes (PMNs) and the transition of solutes and fluids in the alveolar lumen.
      These processes all have a redox component, and this chapter focuses on the role
      played by ROS during the development of ALI/ARDS. We discuss the origins of ROS
      within the cell, cellular defense mechanisms against oxidative damage, the role
      of ROS in the development of endothelial permeability, and potential therapies
      targeted at oxidative stress.

PMID- 29047085
TI  - Redox-Dependent Calpain Signaling in Airway and Pulmonary Vascular Remodeling in
      COPD.
AB  - The calcium-dependent cytosolic, neutral, thiol endopeptidases, calpains, perform
      limited cleavage of their substrates thereby irreversibly changing their
      functions. Calpains have been shown to be involved in several physiological
      processes such as cell motility, proliferation, cell cycle, signal transduction,
      and apoptosis. Overactivation of calpain or mutations in the calpain genes
      contribute to a number of pathological conditions including neurodegenerative
      disorders, rheumatoid arthritis, cancer, and lung diseases. High concentrations
      of reactive oxygen and nitrogen species (RONS) originated from cigarette smoke or
      released by numerous cell types such as activated inflammatory cells and other
      respiratory cells cause oxidative and nitrosative stress contributing to the
      pathogenesis of COPD. RONS and calpain play important roles in the development of
      airway and pulmonary vascular remodeling in COPD. Published data show that
      increased RONS production is associated with increased calpain activation and/or
      elevated calpain protein level, leading to epithelial or endothelial barrier
      dysfunction, neovascularization, lung inflammation, increased smooth muscle cell
      proliferation, and deposition of extracellular matrix protein. Further
      investigation of the redox-dependent calpain signaling may provide future targets
      for the prevention and treatment of COPD.

PMID- 29047086
TI  - Natural Antioxidants as Potential Therapy, and a Promising Role for Melatonin
      Against Pulmonary Hypertension.
AB  - Plasma and serum samples, and lung/heart tissue of pulmonary hypertension (PH)
      patients and animal models of PH display elevated oxidative stress. Moreover, the
      severity of PH and levels of oxidative stress increase concurrently, which
      suggests that oxidative stress could be utilized as a biomarker for PH
      progression. Accumulating evidence has well established that oxidative stress is
      also key role player in the development of PH. Preclinical studies have
      demonstrated that natural antioxidants improved PH condition, and, therefore,
      antioxidant therapy has been proposed as a potential therapeutic strategy against
      PH. These natural antioxidants include medicinal plant extracts and compounds
      such as resveratrol and melatonin. Recent studies suggest that melatonin provides
      health benefit against PH, by enhancing antioxidant capacity, increasing
      vasodilation, counteracting lung and cardiac fibrosis, and stunting right
      ventricular (RV) hypertrophy/failure. This chapter comprehensively reviews and
      discusses a variety of natural antioxidants and their efficacy in modulating
      experimental PH. This chapter also demonstrates that antioxidant therapy remains
      a therapeutic strategy for PH, and particularly identifies melatonin as a safe,
      cost-effective, and promising antioxidant therapy.

PMID- 29047082
TI  - A Brief Overview of Nitric Oxide and Reactive Oxygen Species Signaling in Hypoxia
      Induced Pulmonary Hypertension.
AB  - Pulmonary hypertension (PH) is characterized by increased vasoconstriction and
      smooth muscle cell hyperplasia driving pathological vascular remodeling of
      arterial vessels. In this short review, we discuss the primary source of reactive
      oxygen species (ROS) and nitric oxide (NO) relevant to PH and the mechanism by
      which dysregulation of their production contributes to PH. Specifically, hypoxia
      induced PH is associated with diminished endothelial nitric oxide synthase (eNOS)
      derived NO production and increased production of superoxide (O2*-) through eNOS
      uncoupling and defective mitochondrial respiration. This drives the inhibition of
      the NO/soluble guanylate cyclase (sGC) pathway and activation of the
      transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) with
      consequential dysregulation of the pulmonary vasculature. Therapeutics aimed at
      increasing NO or cGMP bioavailabilities are amenable to hypoxia disease-induced
      PH. Similarly, strategies targeting HIF-1alpha are now considered. Overall,
      pulmonary hypertension including hypoxia-induced PH offers unique opportunities
      for the rational development of therapeutics centered on modulating redox
      signaling.

PMID- 29047087
TI  - Effects of Hyperoxia on the Developing Airway and Pulmonary Vasculature.
AB  - Although it is necessary and part of standard practice, supplemental oxygen (40
      90% O2) or hyperoxia is a significant contributing factor to development of
      bronchopulmonary dysplasia, persistent pulmonary hypertension, recurrent
      wheezing, and asthma in preterm infants. This chapter discusses hyperoxia and the
      role of redox signaling in the context of neonatal lung growth and disease. Here,
      we discuss how hyperoxia promotes dysfunction in the airway and the known redox
      mediated mechanisms that are important for postnatal vascular and alveolar
      development. Whether in the airway or alveoli, redox pathways are important and
      greatly influence the neonatal lung.

PMID- 29047088
TI  - Lung Ischaemia-Reperfusion Injury: The Role of Reactive Oxygen Species.
AB  - Lung ischaemia-reperfusion injury (LIRI) occurs in many lung diseases and during
      surgical procedures such as lung transplantation. The re-establishment of blood
      flow and oxygen delivery into the previously ischaemic lung exacerbates the
      ischaemic injury and leads to increased microvascular permeability and pulmonary
      vascular resistance as well as to vigorous activation of the immune response.
      These events initiate the irreversible damage of the lung with subsequent oedema
      formation that can result in systemic hypoxaemia and multi-organ failure.
      Alterations in the production of reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) have been suggested as crucial mediators of such responses
      during ischaemia-reperfusion in the lung. Among numerous potential sources of
      ROS/RNS within cells, nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidases, xanthine oxidases, nitric oxide synthases and mitochondria have been
      investigated during LIRI. Against this background, we aim to review here the
      extensive literature about the ROS-mediated cellular signalling during LIRI, as
      well as the effectiveness of antioxidants as treatment option for LIRI.

PMID- 29047090
TI  - Metabolic Reprogramming and Redox Signaling in Pulmonary Hypertension.
AB  - Pulmonary hypertension is a complex disease of the pulmonary vasculature, which
      in severe cases terminates in right heart failure. Complex remodeling of
      pulmonary arteries comprises the central issue of its pathology. This includes
      extensive proliferation, apoptotic resistance and inflammation. As such, the
      molecular and cellular features of pulmonary hypertension resemble hallmark
      characteristics of cancer cell behavior. The vascular remodeling derives from
      significant metabolic changes in resident cells, which we describe in detail. It
      affects not only cells of pulmonary artery wall, but also its immediate
      microenvironment involving cells of immune system (i.e., macrophages). Thus
      aberrant metabolism constitutes principle component of the cancer-like theory of
      pulmonary hypertension. The metabolic changes in pulmonary artery cells resemble
      the cancer associated Warburg effect, involving incomplete glucose oxidation
      through aerobic glycolysis with depressed mitochondrial catabolism enabling the
      fueling of anabolic reactions with amino acids, nucleotides and lipids to sustain
      proliferation. Macrophages also undergo overlapping but distinct metabolic
      reprogramming inducing specific activation or polarization states that enable
      their participation in the vascular remodeling process. Such metabolic synergy
      drives chronic inflammation further contributing to remodeling. Enhanced
      glycolytic flux together with suppressed mitochondrial bioenergetics promotes the
      accumulation of reducing equivalents, NAD(P)H. We discuss the enzymes and
      reactions involved. The reducing equivalents modulate the regulation of proteins
      using NAD(P)H as the transcriptional co-repressor C-terminal binding protein 1
      cofactor and significantly impact redox status (through GSH, NAD(P)H oxidases,
      etc.), which together act to control the phenotype of the cells of pulmonary
      arteries. The altered mitochondrial metabolism changes its redox poise, which
      together with enhanced NAD(P)H oxidase activity and reduced enzymatic antioxidant
      activity promotes a pro-oxidative cellular status. Herein we discuss all
      described metabolic changes along with resultant alterations in redox status,
      which result in excessive proliferation, apoptotic resistance, and inflammation,
      further leading to pulmonary arterial wall remodeling and thus establishing
      pulmonary artery hypertension pathology.

PMID- 29047091
TI  - Hydrogen Sulfide as an O2 Sensor: A Critical Analysis.
AB  - There is increasing interest in the physiological actions and therapeutic
      potential of the gasotransmitter hydrogen sulfide (H2S). In addition to exerting
      antihypertensive, anti-inflammatory, antioxidant, and pro-angiogenic effects, H2S
      has been suggested to play a central and ubiquitous role in O2 sensing. According
      to this concept, because H2S is metabolized by oxidation, its cellular
      concentration varies inversely with the ambient pO2 such that hypoxia causes a
      rise in intracellular [H2S]; this then acts to induce appropriate cellular
      responses. In particular, it has been proposed that H2S underpins O2 sensing in
      the carotid body, which triggers increases in ventilation in response to
      hypoxemia, and also in pulmonary arteries, which constrict in response to local
      alveolar hypoxia. This process, termed hypoxic pulmonary vasoconstriction (HPV),
      acts to divert blood to better-oxygenated regions of the lung, thereby
      maintaining the ventilation-perfusion ratio and minimizing hypoxia-induced falls
      in blood O2 saturation. In this chapter, we present a critical review of the
      evidence supporting and questioning this model in both HPV and the carotid body.

PMID- 29047092
TI  - Redox Signaling and Persistent Pulmonary Hypertension of the Newborn.
AB  - Reactive oxygen species (ROS) are redox-signaling molecules that are critically
      involved in regulating endothelial cell functions, host defense, aging, and
      cellular adaptation. Mitochondria are the major sources of ROS and important
      sources of redox signaling in pulmonary circulation. It is becoming increasingly
      evident that increased mitochondrial oxidative stress and aberrant signaling
      through redox-sensitive pathways play a direct causative role in the pathogenesis
      of many cardiopulmonary disorders including persistent pulmonary hypertension of
      the newborn (PPHN). This chapter highlights redox signaling in endothelial cells,
      antioxidant defense mechanism, cell responses to oxidative stress, and their
      contributions to disease pathogenesis.

PMID- 29047089
TI  - Redox Mechanisms Influencing cGMP Signaling in Pulmonary Vascular Physiology and
      Pathophysiology.
AB  - The soluble form of guanylate cyclase (sGC) and cGMP signaling are major
      regulators of pulmonary vasodilation and vascular remodeling that protect the
      pulmonary circulation from hypertension development. Nitric oxide, reactive
      oxygen species, thiol and heme redox, and heme biosynthesis control mechanisms
      regulating the production of cGMP by sGC. In addition, a cGMP-independent
      mechanism regulates protein kinase G through thiol oxidation in manner controlled
      by peroxide metabolism and NADPH redox. Multiple aspects of these regulatory
      processes contribute to physiological and pathophysiological regulation of the
      pulmonary circulation, and create potentially novel therapeutic targets for the
      treatment of pulmonary vascular disease.

PMID- 29047093
TI  - Cross Talk Between Mitochondrial Reactive Oxygen Species and Sarcoplasmic
      Reticulum Calcium in Pulmonary Arterial Smooth Muscle Cells.
AB  - Hypoxic pulmonary vasoconstriction (HPV) occurs during both fetal and postnatal
      development and plays a critical role in matching regional alveolar perfusion
      with ventilation in humans and animals. HPV also contributes significantly to the
      development of pulmonary hypertension. Although the molecular mechanisms of HPV
      and pulmonary hypertension remain incompletely understood, increasing evidence
      demonstrates that hypoxia induces an elevated intracellular reactive oxygen
      species concentration ([ROS]i) in pulmonary artery smooth muscle cells (PASMCs).
      The increased [ROS]i is attributed to the mitochondrial electron transport chain
      (ETC) and plasmalemmal NADPH oxidase (NOX); however, the mitochondrial ETC is a
      primary source for the elevated [ROS]i. Our studies reveal that mitochondrial ROS
      can specifically increase the activity of protein kinase C-epsilon, activate NOX,
      and then induce more ROS production (i.e., ROS-induced ROS production, RIRP).
      Mitochondrial ROS production is principally mediated by Rieske iron-sulfur
      protein (RISP) at the complex III. The increased [ROS]i causes an elevation of
      intracellular Ca2+ concentration ([Ca2+]i), thereby leading to HPV and associated
      pulmonary hypertension. Ryanodine receptor-2 (RyR2)/Ca2+ release channel on the
      sarcoplasmic reticulum (SR) serves as a most valuable player in the elevated
      [Ca2+]i. Our recent data indicate that RyR2-induced Ca2+ release can enhance RISP
      mediated increase in mitochondrial ROS concentration ([ROS]mito), and that the
      mitochondrial Ca2+ uniporter is involved in elevating [ROS]mito. Based on the
      existing reports and our unpublished data, we conclude that the cross talk
      between [ROS]mito and [Ca2+]i, that is RISP-dependent mitochondrial ROS-induced
      RyR2-mediated SR Ca2+ release (ROS-induced Ca2+ release, RICR) and RyR2-mediated
      SR Ca2+ release-induced RISP-dependent mitochondrial ROS production (Ca2+-induced
      ROS production, CIRP), may form a positive reciprocal loop in mediating HPV and
      also possibly pulmonary hypertension.

PMID- 29047094
TI  - Endothelial Cell Reactive Oxygen Species and Ca2+ Signaling in Pulmonary
      Hypertension.
AB  - Pulmonary hypertension (PH) refers to a disorder characterized by elevated
      pulmonary arterial pressure, leading to right ventricular overload and eventually
      right ventricular failure, which results in high morbidity and mortality. PH is
      associated with heterogeneous etiologies and distinct molecular mechanisms,
      including abnormal migration and proliferation of endothelial and smooth muscle
      cells. Although the exact details are not fully elucidated, reactive oxygen
      species (ROS) have been shown to play a key role in promoting abnormal function
      in pulmonary arterial smooth muscle and endothelial cells in PH. In endothelial
      cells, ROS can be generated from sources such as NADPH oxidase and mitochondria,
      which in turn can serve as signaling molecules in a wide variety of processes
      including posttranslational modification of proteins involved in Ca2+
      homeostasis. In this chapter, we discuss the role of ROS in promoting abnormal
      vasoreactivity and endothelial migration and proliferation in various models of
      PH. Furthermore, we draw particular attention to the role of ROS-induced
      increases in intracellular Ca2+ concentration in the pathobiology of PH.

PMID- 29047095
TI  - Redox Signaling in the Right Ventricle.
AB  - Pulmonary hypertension is a devastating disease without cure. The major cause of
      death among patients with pulmonary hypertension is right heart failure; however,
      biology of the right heart is not well understood. This lack of knowledge
      interferes with developing effective therapeutic strategies to treat these
      patients. In this chapter, we summarize studies performed in our laboratory that
      investigated the role of redox signaling in the regulation of the right ventricle
      (RV), using rat models of experimental pulmonary hypertension and right heart
      failure. Specifically, this chapter covers the topics of (a) redox regulation of
      serotonin signaling in the RV, (b) the carbonylation-degradation pathway of
      signal transduction in RV hypertrophy and (c) oxidative modifications in the RV
      of the SU5416/ovalbumin model of pulmonary arterial hypertension. These studies
      revealed that redox regulation in the RV is complex and simply giving lots of
      antioxidants to patients will unlikely benefit them. Deeper understanding of
      specific and selective redox mechanisms should shed light on how we can develop
      therapeutic strategies by modulating redox reactions.

PMID- 29047096
TI  - Hypoxia and Local Inflammation in Pulmonary Artery Structure and Function.
AB  - Hypoxia is recognized as a contributor to pulmonary vascular diseases such as
      pulmonary hypertension. Hypoxia-induced inflammatory changes can enhance
      structural and functional changes in pulmonary artery (PA) in the context of PH.
      Accordingly, understanding how hypoxia and inflammation are linked in the context
      of pulmonary artery structure and function could be relevant towards development
      of novel therapies for PH. In this regard, factors such as thymic stromal
      lymphopoietin (TSLP), an inflammatory cytokine, and brain-derived neurotrophic
      factor (BDNF), a neurotrophin, have been found critical for nonvascular systems
      such as airway and asthma. While TSLP canonically affects the immune system, in
      nonvascular systems, noncanonical effects such as altered [Ca2+]i and cell
      proliferation have been noted: aspects also relevant to the PA, where there is
      currently little to no data. Similarly, better known in the nervous system, there
      is increasing evidence that BDNF is locally produced by structural cells of the
      airway and can contribute to asthma pathophysiology. In this chapter, we
      summarize the potential relevance of factors such as TSLP and BDNF to the PA and
      in the context of hypoxia influences towards development of PH. We focus on cell
      sources and targets such as PA endothelial cells (PAECs) and smooth muscle cells
      (PASMCs), and the effects of TSLP or BDNF on intracellular Ca2+ responses to
      vasoconstrictor agonist, cell proliferation, and potential signaling cascades
      involved.

PMID- 29047097
TI  - From Physiological Redox Signalling to Oxidant Stress.
AB  - Oxidant stress is strongly associated with cardiovascular disease, including
      pulmonary hypertension, but antioxidant therapies have so far proven ineffective.
      This is partly due to a lack of understanding of the key role played by reactive
      oxygen species (ROS) in physiological cell signalling, and partly to the complex
      interrelationships between generators of ROS (e.g. mitochondria and NADPH
      oxidases, NOX), cellular antioxidant systems and indeed Ca2+ signalling. At
      physiological levels ROS reversibly affect the function of numerous enzymes and
      transcription factors, most often via oxidation of specific protein thiols.
      Importantly, they also affect pathways that promote ROS generation by NOX or
      mitochondria (ROS-induced ROS release), which has an inherent propensity for
      positive feedback and uncontrolled oxidant production. The reason this does not
      occur under normal conditions reflects in part a high level of
      compartmentalisation of ROS signalling within the cell, akin to that for Ca2+.
      This article considers the physiological processes which regulate NOX and
      mitochondrial ROS production and degradation and their interactions with each
      other and Ca2+ signalling pathways, and discusses how loss of spatiotemporal
      constraints and activation of positive feedback pathways may impact on their
      dysregulation in pulmonary hypertension.

PMID- 29047098
TI  - Emerging Role of MicroRNAs and Long Noncoding RNAs in Healthy and Diseased Lung.
AB  - Pulmonary hypertension (PH) is a complex and multifactorial disease. An inability
      to fully unravel the molecular complexities has led to various clinical
      challenges in developing new therapies for this disease. Noncoding RNAs (ncRNAs)
      are RNA molecules with limited ability of coding proteins. The amount of ncRNAs
      is up to 98% of the whole genome's transcripts. Many ncRNAs with a regulatory
      function of genes have been identified to date and found to act at various steps
      along the protein biosynthetic process, which includes transcription, RNA
      maturation, translation, and protein degradation. These discoveries are fueling a
      new era in understanding the pathophysiology and therapeutic pathways of PH. In
      this chapter, we discuss the emerging role of noncoding RNAs in PH as well as
      other pulmonary diseases.

PMID- 29047099
TI  - Techniques for Detecting Reactive Oxygen Species in Pulmonary Vasculature Redox
      Signaling.
AB  - Redox signaling plays important roles in regulating pulmonary vasculature
      function. Aberrant redox signaling, e.g., overproduction of reactive oxygen
      species (ROS) that exceeds the capability of cellular antioxidant mechanisms, has
      been found to alter vasculature function and remodel blood vessel structure, thus
      contributes to pathological processes of pulmonary vasculature. The regulation of
      pulmonary vasculature via ROS is a very complicated process with various
      biological events involved, however, the specific effect of individual ROS and
      the underlying mechanism still remain unclear. Most of ROS are present as free
      radical forms with extremely short lifetime, which makes it very difficult to
      detect the ROS and investigate their bioactivities. Therefore, developing
      specific and sensitive methods to detect ROS in complex biological system is
      essential for us to advance our knowledge in pulmonary vasculature regulation. In
      this chapter, we introduce several commonly used techniques for the detection of
      ROS in vitro and in vivo, including chemiluminescence-based assay, fluorescence
      based assay, cytochrome c reduction method, genetically encoded fluorescent
      probes, as well as ESR spin trapping technique. We also discuss the advantages,
      limitations, and recent technical advances of each individual technique as well
      as their applications in pulmonary vasculature studies. We believe that technical
      advance in the detection of ROS will provide us with a better understanding on
      how to maintain normal pulmonary vasculature functions under oxidative stress.

PMID- 29047101
TI  - Subcellular Redox Signaling.
AB  - Oxidative and antioxidative system of cells and tissues maintains a balanced
      state under physiological conditions. A disruption in this balance of redox
      status has been associated with numerous pathological processes. Reactive oxygen
      species (ROS) as a major redox signaling generates in a spatiotemporally
      dependent manner. Subcellular organelles such as mitochondria, endoplasmic
      reticulum, plasma membrane and nuclei contribute to the production of ROS. In
      addition to downstream effects of ROS signaling regulated by average ROS changes
      in cytoplasm, whether subcelluar ROS mediate biological effect(s) has drawn
      greater attentions. With the advance in redox-sensitive probes targeted to
      different subcellular compartments, the investigation of subcellular ROS
      signaling and its associated cellular function has become feasible. In this
      review, we discuss the subcellular ROS signaling, with particular focus on
      mechanisms of subcellular ROS production and its downstream effects.

PMID- 29047102
TI  - Reactive Oxygen Species in COPD-Related Vascular Remodeling.
AB  - The pathogenesis of chronic obstructive pulmonary disease (COPD) is a
      multifaceted process involving the alteration of pulmonary vasculature. Such
      vascular remodeling can be associated with inflammation, shear stress, and
      hypoxia-conditions commonly seen in patients with lung diseases. Particularly,
      the overproduction of reactive oxygen species (ROS) in the diseased lungs
      contributes greatly to pulmonary vascular remodeling. ROS play an important role
      in vascular homeostasis, yet excessive ROS can alter pulmonary vasculature and
      impair lung function, as implicated in COPD at all stages. Increased inflammatory
      cell infiltration and endothelial dysfunction both correspond to the severity of
      COPD. As a byproduct of vascular remodeling, pulmonary hypertension negatively
      affects the long-term survival rate of COPD patients. While there is currently no
      cure for COPD, several treatment options have focused on alleviating COPD
      symptoms. Interventions such as long-term oxygen therapy, endothelium-targeted
      treatment, and pharmacological therapies show promising results in improving the
      life span of COPD patients and attenuating the progression of pulmonary
      hypertension. In this chapter, we aim to discuss the contributing factors of
      pulmonary vascular remodeling in COPD with an emphasis on the ROS, as well as
      potential redox treatments for COPD-related vascular remodeling.

PMID- 29047100
TI  - Mitochondrial and Metabolic Drivers of Pulmonary Vascular Endothelial Dysfunction
      in Pulmonary Hypertension.
AB  - Pulmonary hypertension (PH) is a deadly and increasingly prevalent vascular
      disease characterized by excessive pulmonary vascular remodeling and right
      ventricular dysfunction which leads to right heart failure, multiorgan
      dysfunction, and premature death. The cause of the vascular remodeling in PH
      remains elusive, and thus current treatments are marginally effective and
      prognosis of PH remains poor. Increasing evidence indicates the pathogenic
      importance of endothelial dysfunction in PH. However, the underlying mechanisms
      of such dysfunction are not well described. Endothelial apoptosis and
      hyperproliferation have been identified in patients with PH. Both are linked with
      the increased oxidative stress and inflammatory responses, and are influenced by
      various genetic and exogenous stresses. Importantly, contrary to historic dogma
      that suggested a negligible role for mitochondria and energy balance in
      endothelial pathology, recent findings have implicated the role of endothelial
      metabolism directly in PH. This chapter addresses the emerging role of
      mitochondria in pulmonary vascular endothelial dysfunction in PH. A more
      sophisticated understanding of the biochemical, metabolic, molecular, and
      physiologic underpinnings of this emerging paradigm should enable the development
      of a new generation of targeted therapies that will stunt or reverse pulmonary
      vascular remodeling.

PMID- 29047103
TI  - Correction to: adjacent level disease-background and update based on disc
      replacement data.
AB  - This article was published and transmitted with the lead author's name listed
      incorrectly in the citation. The correct citation is, in full: Kaye, I.D. &
      Hilibrand, A.S. Curr Rev Musculoskelet Med (2017) 10: 147.
      https://doi.org/10.1007/s12178-017-9396-5 .

PMID- 29047104
TI  - Discrepancies in reference values of soluble Triggering Receptor Expressed on
      Myelocytes 1 (sTREM-1) question the reliability of related studies.

PMID- 29047105
TI  - gamma-Secretase inhibitor reduces immunosuppressive cells and enhances tumour
      immunity in head and neck squamous cell carcinoma.
AB  - Immune evasion is a hallmark feature of cancer, and it plays an important role in
      tumour initiation and progression. In addition, tumour immune evasion severely
      hampers the desired antitumour effect in multiple cancers. In this study, we
      aimed to investigate the role of the Notch pathway in immune evasion in the head
      and neck squamous cell carcinoma (HNSCC) microenvironment. We first demonstrated
      that Notch1 signaling was activated in a Tgfbr1/Pten-knockout HNSCC mouse model.
      Notch signaling inhibition using a gamma-secretase inhibitor (GSI-IX, DAPT)
      decreased tumour burden in the mouse model after prophylactic treatment. In
      addition, flow cytometry analysis indicated that Notch signaling inhibition
      reduced the sub-population of myeloid-derived suppressor cells (MDSCs), tumour
      associated macrophages (TAMs) and regulatory T cells (Tregs), as well as immune
      checkpoint molecules (PD1, CTLA4, TIM3 and LAG3), in the circulation and in the
      tumour. Immunohistochemistry (IHC) of human HNSCC tissues demonstrated that
      elevation of the Notch1 downstream target HES1 was correlated with MDSC, TAM and
      Treg markers and with immune checkpoint molecules. These results suggest that
      modulating the Notch signaling pathway may decrease MDSCs, TAMs, Tregs and immune
      checkpoint molecules in HNSCC.

PMID- 29047106
TI  - Extracellular 5'-nucleotidase (CD73) promotes human breast cancer cells growth
      through AKT/GSK-3beta/beta-catenin/cyclinD1 signaling pathway.
AB  - To identify the role and to explore the mechanism of extracellular 5'
      nucleotidase (CD73) in human breast cancer growth, CD73 expression was measured
      firstly in breast cancer tissues and cell lines, and then interfered with or over
      expressed by recombinant lentivirus in cell lines. Impacts of CD73 on breast
      cancer cell proliferation and cell cycle were investigated with colony formation
      assay, CCK-8 and flow cytometry. The relationship between CD73 and AKT/GSK
      3beta/beta-catenin pathway was assessed with adenosine, adenosine 2A receptor
      antagonist (SCH-58261), adenosine 2A receptor agonist (NECA), CD73 enzyme
      inhibitor (APCP) and Akt inhibitor (MK-2206). Moreover, the effect of CD73 on
      breast cancer growth in vivo was examined with human breast cancer transplanting
      model of nude mice. The results showed that the expression of CD73 was high in
      breast cancer tissues and increased with advanced tumor grades and lympho-node
      status. CD73 expression was higher in more malignant cells, and CD73
      overexpression promoted breast cancer cell proliferation in both in vivo and in
      vitro. It activated AKT/GSK-3beta/beta-catenin/cyclinD1 signaling pathway through
      CD73 enzyme activity and other mechanism.

PMID- 29047107
TI  - Hybrid organic-inorganic CH3 NH3 PbI3 perovskite building blocks: Revealing ultra
      strong hydrogen bonding and mulliken inner complexes and their implications in
      materials design.
AB  - Methylammonium lead iodide (CH3 NH3 PbI3 ) perovskite compound has produced a
      remarkable breakthrough in the photovoltaic history of solar cell technology
      because of its outstanding device-based performance as a light-harvesting
      semiconductor. Whereas the experimental and theoretical studies of this system in
      the solid state have been numerously reported in the last 4 years, its
      fundamental cluster physics is yet to be exploited. To this end, this study has
      performed theoretical investigations using DFT-M06-2X/ADZP to examine the
      principal geometrical, electronic, topological, and orbital properties of the CH3
      NH3 PbI3 molecular building block. The intermolecular hydrogen bonded
      interactions examined for the most important conformers of the system are found
      to be unusually strong, with binding energies lying between -93.53 and -125.11
      kcal mol-1 (beyond the covalent limit, -40 kcal mol-1 ), enabling us to classify
      the underlying interactions as ultra-strong type since their characteristic
      properties are unidentical with those have already been proposed as very strong,
      strong, moderate, weak, and van der Waals. Based on this, together with the
      unusually high charge transfers, strong hyperconjugative interactions,
      sophisticated topologies of the charge density, and short intermolecular
      distances of separation, we have characterized the conformers of CH3 NH3 PbI3 as
      Mulliken inner complexes. The consequences of these, as well as of the ultra
      strong interactions, in designing novel functional nanomaterials are outlined.
      (c) 2017 Wiley Periodicals, Inc.

PMID- 29047109
TI  - Metabolic flux towards the (iso)flavonoid pathway in lignin modified alfalfa
      lines induces resistance against Fusarium oxysporum f. sp. medicaginis.
AB  - Downregulation of lignin in alfalfa (Medicago sativa L.) is associated with
      increased availability of cell wall polysaccharides in plant cells. We tested
      transgenic alfalfa plants downregulated for Caffeoyl-CoA O-methyltransferase
      (CCoAOMT) against an economically important fungal disease of alfalfa, Fusarium
      wilt caused by Fusarium oxysporum f. sp. medicaginis, and found it more resistant
      to this disease. Transcriptomic and metabolomic analyses indicated that the
      improved disease resistance against Fusarium wilt is due to increased
      accumulation and/or spillover of flux towards the (iso)flavonoid pathway. Some
      (iso)flavonoids and their pathway intermediate compounds showed strong
      accumulation in CCoAOMT downregulated plants after F. oxysporum f. sp.
      medicaginis inoculation. The identified (iso)flavonoids, including medicarpin and
      7,4'-dihydroxyflavone, inhibited the in vitro growth of F. oxysporum f. sp.
      medicaginis. These results suggested that the increased accumulation and/or
      shift/spillover of flux towards the (iso)flavonoid pathway in CCoAOMT
      downregulated plants is associated with induced disease resistance.

PMID- 29047108
TI  - Clinicopathologic characteristics and outcomes of transformed diffuse large B
      cell lymphoma in hepatitis C virus-infected patients.
AB  - Hepatitis C virus (HCV) causes a chronic but curable infection associated with
      the development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma
      (DLBCL). Preliminary data have shown frequent transformation of indolent lymphoma
      to DLBCL in HCV-infected patients. To compare their clinicopathologic
      characteristics and oncologic outcomes, we reviewed the medical records and
      pathology reports of HCV-infected and uninfected patients with DLBCL that
      transformed from indolent lymphoma seen at The University of Texas MD Anderson
      Cancer Center (June 2004 to May 2015). To identify predictors of DLBCL relapse,
      patients with relapse after first-line chemotherapy were compared with those
      without it using univariate and logistic regression analyses. Compared with the
      uninfected patients (n = 63), HCV-infected patients (n = 21) were younger (median
      age =54 years [interquartile range= 49-62 years] vs. 62 years [53-66 years]; p =
      0.01) and more often had advanced DLBCL (Ann Arbor stage 3-4; 95% vs. 76%; p =
      0.05). Immunophenotypically, more HCV-infected than uninfected patients had CD10
      negative B cells (76% vs. 43%; p = 0.008), CD5-positive B cells (39% vs. 7%; p =
      0.004) and activated B-cell phenotypes (57% vs. 31%; p = 0.07). Comparison of the
      patients who had relapse after first-line chemotherapy (n = 42) and those who did
      not (n = 40) revealed that having CD5-positive B cells was the only factor
      associated with DLBCL relapse in multivariate analysis (odds ratio= 10.7; p =
      0.02). HCV-infected patients with transformed DLBCL have unique clinicopathologic
      characteristics that make their lymphoma difficult to treat, potentially leading
      to unfavorable outcome. The impact of HCV eradication should be explored in such
      patients.

PMID- 29047111
TI  - Primary cutaneous aggressive epidermotropic cytotoxic CD8+ T-cell lymphoma: long
      term remission after brentuximab vedotin.

PMID- 29047110
TI  - Cytoskeleton and ECM tumor mutant peptides: Increased protease sensitivities and
      potential consequences for the HLA class I mutant epitope reservoir.
AB  - Cytoskeleton and extracellular matrix-related proteins (CECMPs) represent the
      most common class of cancer mutants, owing to the large size of their coding
      regions and the randomness of mutagenesis. We used a bioinformatics approach to
      assess the impact of amino acid (AA) substitutions on the sensitivity of CECMPs
      to proteases relevant to melanoma and on the binding affinities for HLA class I.
      CECMP peptides with AA substitutions overwhelmingly reflect increased sensitivity
      to proteases implicated in melanoma development (MME, CTSS, MMP2, CTSD, CTSL) in
      comparison to the wild-type peptide sequences. Furthermore, peptides with AA
      substitutions representing increased peptide protease sensitivity also
      represented relatively high binding affinities for HLA class I allelic variants.
      These analyses raise the question of whether increased protease sensitivity, of
      mutant cancer peptides represents a significant increase in the availability of
      cancer mutant, HLA class I epitopes and a hitherto unappreciated aspect of cancer
      cell immunogenicity, particularly in the case of melanoma?

PMID- 29047112
TI  - Clinical and dermoscopic characteristics of a patient with cutaneous and mucosal
      manifestations of Peruvian wart.

PMID- 29047113
TI  - Second primary cutaneous T-cell lymphoma in patients with non-Hodgkin lymphoma: a
      chicken-or-the-egg issue.

PMID- 29047114
TI  - Complications following laryngeal sacculectomy in brachycephalic dogs.
AB  - OBJECTIVES: To evaluate the effect of sacculectomy on the immediate postoperative
      complication rate in dogs affected with brachycephalic obstructive airway
      syndrome. MATERIALS AND METHODS: Retrospective review of clinical records of
      brachycephalic dogs with everted saccules that underwent surgery for
      brachycephalic obstructive airway syndrome between 2009 and 2014. Dogs were
      grouped as those having nares resection and staphylectomy only and those having
      nares resection, staphylectomy and laryngeal sacculectomy. Complications were
      scored as mild, moderate or severe. RESULTS: In total, 37 dogs were included in
      the sacculectomy group and 44 in the comparator group. Dogs that had undergone
      sacculectomy were more likely to develop postoperative complications, with 18 of
      37 developing complications, nine of which were moderate to severe. In the group
      without sacculectomy, nine of 44 dogs developed complications, of which one was
      severe. Different breed distribution between groups might also impact this
      outcome. CLINICAL SIGNIFICANCE: The results suggest that sacculectomy might
      increase morbidity following brachycephalic airway surgery, but repeat studies
      are required to confirm this result. Further information is also required to
      determine whether the short-term risks of sacculectomy are outweighed by superior
      long-term functional outcome.

PMID- 29047115
TI  - Response to the letter to the editor by Gkougkourelas et al - EJCI-2017-0361.

PMID- 29047116
TI  - Novel mutations in KLF1 encoding the In(Lu) phenotype reflect a diversity of
      clinical presentations.
AB  - BACKGROUND: Mutation in the KLF1 gene is the cause of the In(Lu) (Inhibitor of
      Lutheran) Lu(a-b-) phenotype and more than 60 alleles have been associated with
      this phenotype. Here we describe findings from investigation of seven cases: six
      presenting with a Lu(a-b-) phenotype including the historical index case and one
      referred from a patient with chronic anemia. STUDY DESIGN AND METHODS: Serologic
      testing was by standard methods. DNA testing included amplification and
      sequencing of KLF1 and LU coding regions. A StuI polymerase chain reaction
      restriction fragment length polymorphism was designed to target c.304T>C in KLF1.
      RESULTS: Five different KLF1 alleles were identified. Three are new: KLF1*90A
      (p.Trp30Ter), KLF*911A (p.Thr304Lys), and KLF1*304C,318G (p. Ser102Pro,
      Tyr106Ter) present in two unrelated individuals. Two, including the index case,
      had c.954dupG (p.Arg319Glufs*34), that is, KLF1*BGM06. The child with unexplained
      anemia had c.973G>A (p.Glu325Lys), associated with congenital dyserythropoietic
      anemia. The common c.304T>C was found in two of the seven samples investigated
      and in 60 of 100 blood donors. CONCLUSION: Mutations in KLF1 are pleiotropic and
      although most are benign, others are associated with hematologic abnormalities.
      We report three new KLF1 alleles associated with benign In(Lu) and document both
      the molecular basis of the original In(Lu) phenotype using a frozen sample stored
      for more than 50 years and the cause of unexplained anemia in a child. We also
      confirm previous observations that c.304C (p.102Pro) is not, by itself,
      associated with an In(Lu) phenotype in donors self-identified as U.S. minorities.

PMID- 29047117
TI  - Dermographism in a patient with fever.

PMID- 29047118
TI  - Modeling Community Discharge of Medicaid Nursing Home Residents: Implications for
      Money Follows the Person.
AB  - OBJECTIVE: To build and test a model that predicts community discharge
      probabilities for Medicaid-eligible nursing home (NH) residents who remain in the
      nursing home at 90 days after admission and, thus, would be candidates for the
      Money Follows the Person (MFP) program. DATA SOURCE: The Minimum Data Set,
      Medicaid Management Information Systems, and Minnesota Vital Statistics file.
      DATA: Cohort of 33, 590 nursing home stays that qualified for Medicaid by the
      90th day of their stay from 383 Minnesota nursing homes from July 2011 to June
      2013. STUDY DESIGN: Mixed effects logistic regression model to predict community
      discharge. PRINCIPAL FINDINGS: The scoring system had a high level of accuracy in
      predicting community discharge for both the fitting and validation cohorts.
      Subpopulations with severe mental illness or intellectual disability were well
      represented across the entire score range. CONCLUSIONS: Findings are being
      applied in the Minnesota's MFP initiative (Moving Home Minnesota) to target
      Medicaid-eligible NH residents for transitioning to the community. This approach
      could be applied to MFP in other states.

PMID- 29047119
TI  - Vessel diameter is related to amount and spatial arrangement of axial parenchyma
      in woody angiosperms.
AB  - Parenchyma represents a critically important living tissue in the sapwood of the
      secondary xylem of woody angiosperms. Considering various interactions between
      parenchyma and water transporting vessels, we hypothesize a structure-function
      relationship between both cell types. Through a generalized additive mixed model
      approach based on 2,332 woody angiosperm species derived from the literature, we
      explored the relationship between the proportion and spatial distribution of ray
      and axial parenchyma and vessel size, while controlling for maximum plant height
      and a range of climatic factors. When factoring in maximum plant height, we found
      that with increasing mean annual temperatures, mean vessel diameter showed a
      positive correlation with axial parenchyma proportion and arrangement, but not
      for ray parenchyma. Species with a high axial parenchyma tissue fraction tend to
      have wide vessels, with most of the parenchyma packed around vessels, whereas
      species with small diameter vessels show a reduced amount of axial parenchyma
      that is not directly connected to vessels. This finding provides evidence for
      independent functions of axial parenchyma and ray parenchyma in large vesselled
      species and further supports a strong role for axial parenchyma in long-distance
      xylem water transport.

PMID- 29047120
TI  - Dental pulp regeneration via cell homing.
AB  - The typical treatment for irreversibly inflamed/necrotic pulp tissue is root
      canal treatment. As an alternative approach, regenerative endodontics aims to
      regenerate dental pulp-like tissues using two possible strategies: cell
      transplantation and cell homing. The former requires exogenously transplanted
      stem cells, complex procedures and high costs; the latter employs the host's
      endogenous cells to achieve tissue repair/regeneration, which is more clinically
      translatable. This systematic review examines cell homing for dental pulp
      regeneration, selecting articles on in vitro experiments, in vivo ectopic
      transplantation models and in situ pulp revascularization. MEDLINE/PubMed and
      Scopus databases were electronically searched for articles without limits in
      publication date. Two reviewers independently screened and included papers
      according to the predefined selection criteria. The electronic searches
      identified 46 studies. After title, abstract and full-text examination, 10
      articles met the inclusion criteria. In vitro data highlighted that multiple
      cytokines have the capacity to induce migration, proliferation and
      differentiation of dental pulp stem/progenitor cells. The majority of the in vivo
      studies obtained regenerated connective pulp-like tissues with
      neovascularization. In some cases, the samples showed new innervation and new
      dentine deposition. The in situ pulp revascularization regenerated intracanal
      pulp-like tissues with neovascularization, innervation and dentine formation.
      Cell homing strategies for pulp regeneration need further understanding and
      improvement if they are to become a reliable and effective approach in
      endodontics. Nevertheless, cell homing currently represents the most clinically
      viable pathway for dental pulp regeneration.

PMID- 29047121
TI  - In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas
      using reporter gene-based MR imaging.
AB  - Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for
      gene therapy of malignant gliomas due to their property of tumor tropism.
      However, MSCs may show bidirectional and divergent effects on tumor growth.
      Therefore, a robust surveillance system with a capacity for noninvasive
      monitoring of the homing, distribution and fate of stem cells in vivo is highly
      desired for developing stem cell-based gene therapies for tumors. In this study,
      we used ferritin gene-based magnetic resonance imaging (MRI) to track the tumor
      tropism of MSCs in a rat orthotopic xenograft model of malignant glioma. MSCs
      were transduced with lentiviral vectors expressing ferritin heavy chain (FTH) and
      enhanced green fluorescent protein (eGFP). Intra-arterial, intravenous and
      intertumoral injections of these FTH transgenic MSCs (FTH-MSCs) were performed in
      rats bearing intracranial orthotopic C6 gliomas. The FTH-MSCs were detected as
      hypointense signals on T2- and T2*-weighted images on a 3.0 T clinical MRI. After
      intra-arterial injection, 17% of FTH-MSCs migrated toward the tumor and gradually
      diffused throughout the orthotopic glioma. This dynamic process could be tracked
      in vivo by MRI up to 10 days of follow-up, as confirmed by histology. Moreover,
      the tumor tropism of MSCs showed no appreciable impact on the progression of the
      tumor. These results suggest that FTH reporter gene-based MRI can be used to
      reliably track the tropism and fate of MSCs after their systemic transplantation
      in orthotopic gliomas. This real-time in vivo tracking system will facilitate the
      future development of stem cell-based therapies for malignant gliomas.

PMID- 29047122
TI  - The presence of Philadelphia chromosome does not confer poor prognosis in adult
      pre-B acute lymphoblastic leukaemia in the tyrosine kinase inhibitor era - a
      surveillance, epidemiology, and end results database analysis.
AB  - The BCR-ABL1 fusion gene is caused by a translocation between chromosomes 9 and
      22, resulting in an abnormal chromosome 22 (Philadelphia chromosome; Ph). Prior
      to the introduction of tyrosine kinase inhibitors (TKI), the presence of BCR-ABL1
      conferred a poor prognosis in patients with acute lymphoblastic leukaemia (ALL).
      We compared the survival of Ph+ and Ph-ALL during the period when TKIs were
      universally available in the US for Ph+ALL, using a Surveillance, Epidemiology,
      and End Results (SEER) Database analysis. A total of 2694 patients with pre-B ALL
      (206 Ph+ALL; 2488 Ph-ALL) aged >=18 years, who were diagnosed between 2010 and
      2014, were identified in SEER registries. The median overall survival (OS) was 32
      months in Ph+ALL (95% confidence interval [CI] 18 months-not reached) and 27
      months (95% CI 24-30 months) in Ph-ALL (Log-rank test P-value 0.34). Older age
      was associated with worse prognosis in both Ph+ALL and Ph-ALL. Age-adjusted OS
      was inferior in Hispanics and African-Americans compared to non-Hispanic whites.
      Survival of pre-B ALL shows continued improvement with time. Philadelphia
      chromosome status does not confer poor prognosis in pre-B ALL in the TKI era:
      prognostic factors in pre-B ALL should be re-evaluated in the light of this
      finding.

PMID- 29047123
TI  - Parallel implementation of efficient charge-charge interaction evaluation scheme
      in periodic divide-and-conquer density-functional tight-binding calculations.
AB  - A low-computational-cost algorithm and its parallel implementation for periodic
      divide-and-conquer density-functional tight-binding (DC-DFTB) calculations are
      presented. The developed algorithm enables rapid computation of the interaction
      between atomic partial charges, which is the bottleneck for applications to large
      systems, by means of multipole- and interpolation-based approaches for long- and
      short-range contributions. The numerical errors of energy and forces with respect
      to the conventional Ewald-based technique can be under the control of the
      multipole expansion order, level of unit cell replication, and interpolation grid
      size. The parallel performance of four different evaluation schemes combining
      previous approaches and the proposed one are assessed using test calculations of
      a cubic water box on the K computer. The largest benchmark system consisted of
      3,295,500 atoms. DC-DFTB energy and forces for this system were obtained in only
      a few minutes when the proposed algorithm was activated and parallelized over
      16,000 nodes in the K computer. The high performance using a single node
      workstation was also confirmed. In addition to liquid water systems, the
      feasibility of the present method was examined by testing solid systems such as
      diamond form of carbon, face-centered cubic form of copper, and rock salt form of
      sodium chloride. (c) 2017 Wiley Periodicals, Inc.

PMID- 29047124
TI  - When traditional research fails - the case for veno-arterial ECMO in
      postcardiotomy cardiogenic shock.

PMID- 29047125
TI  - How to describe your data - the devil is in the distribution.

PMID- 29047127
TI  - Suxamethonium or rocuronium for rapid sequence induction of anaesthesia? A reply.

PMID- 29047126
TI  - Are aviation industry fatigue risk management strategies needed in healthcare?

PMID- 29047128
TI  - Onset of labour epidural analgesia with low-dose bupivacaine and different doses
      of fentanyl.
AB  - This study investigated the effects of different doses of epidural fentanyl on
      the time to onset of epidural analgesia in women in early labour. We hypothesised
      that onset of epidural labour analgesia (the primary outcome defined as time in
      minutes from completion of epidural bolus to the first uterine contraction with a
      numeric pain rating scale [NPRS] score <= 3) would be faster with 100 MUg of
      fentanyl epidural bolus compared with 20 MUg or 50 MUg. Epidural labour analgesia
      was initiated with 20 MUg of fentanyl (F20 group), 50 MUg (F50 group) or 100 MUg
      (F100 group) along with 10 ml bupivacaine 0.08% as the loading dose. We randomly
      allocated 105 patients, with 35 patients in each group. Median (IQR [range]) time
      to achieve NPRS <= 3 was 18 (11-30 [6-20]) min in F20, 10 (8-19 [4-30]) min in
      F50 and 10 (6-16 [3-30]) min in F100 groups. There was a significant difference
      in onset times comparing F100 with F20 (p < 0.001) and F50 with F20 (p = 0.007),
      but not significantly different comparing F100 with F50 (p = 0.19). The median
      (IQR [range]) time from the epidural loading dose to first patient controlled
      epidural analgesia bolus was 61 min (20-165 [20-420]) in F20, 118 min (66-176 [20
      396]) in F50 and 150 min (66-214 [30-764]) in F100 groups. This was not
      statistically significant (p = 0.16) comparing the F20 with the F100 group. There
      were no significant differences in maternal side-effects, mode of delivery,
      patient satisfaction scores or neonatal Apgar scores between all groups. We
      conclude that the 50 MUg and 100 MUg fentanyl doses were associated with reduced
      onset times to effective analgesia compared with the 20 MUg dose.

PMID- 29047130
TI  - Correction.

PMID- 29047131
TI  - EWTD implementation in anaesthesia: effects on training and quality of life.

PMID- 29047129
TI  - The use of activated charcoal filters in anaesthetic circuits in suspected
      malignant hyperthermia.

PMID- 29047132
TI  - Errors in published papers are multifactorial.

PMID- 29047133
TI  - Corrections.

PMID- 29047134
TI  - Curtailing fabrication in medical literature.

PMID- 29047135
TI  - Iliac artery balloon catheter use in abnormally invasive placenta disease
      management - a reply.

PMID- 29047137
TI  - Are aviation industry fatigue risk management strategies needed in healthcare? A
      reply.

PMID- 29047136
TI  - Apnoeic oxygenation with high-flow nasal oxygen for laryngeal surgery: a case
      series.
AB  - Surgery under apnoeic conditions with the use of high-flow nasal oxygen is novel.
      Between November 2016 and May 2017, 28 patients underwent tubeless laryngeal or
      tracheal surgery under apnoeic conditions with high-flow nasal oxygen as the sole
      method of gas exchange. Patients received total intravenous anaesthesia and
      neuromuscular blocking agents for the duration of their surgery. The median (IQR
      [range]) apnoea time was 19 (15-24 [9-37]) min. Four patients experienced an
      episode of oxygen desaturation to a value between 85% and 90%, lasting less than
      2 min in each case. Median (IQR [range]) end-tidal carbon dioxide (ETCO2 ) level
      following apnoea was 8.2 (7.2-9.4 [5.8-11.8]) kPa. The mean (SD) rate of ETCO2
      increase was 0.17 (0.07) kPa.min-1 from an approximated baseline value of 5.00
      kPa. Venous blood sampling from 19 patients demonstrated a mean (SD) partial
      pressure of carbon dioxide (PV CO2 ) of 6.29 (0.71) kPa at baseline and 9.44
      (1.12) kPa after 15 min of apnoea. This equates to a mean (SD) PV CO2 rise of
      0.21 (0.08) kPa.min-1 during this period. Mean (SD) pH was 7.40 (0.03) at
      baseline and 7.23 (0.04) after 15 min of apnoea. Mean (SD) standard bicarbonate
      was 26.7 (1.8) mmol.l-1 at baseline and 25.4 (1.8) mmol.l-1 at 15 min. We
      conclude that high-flow nasal oxygen under apnoeic conditions can provide
      satisfactory gas exchange in order to allow tubeless anaesthesia for laryngeal
      surgery.

PMID- 29047138
TI  - Improving TIVA safety through measurement of peripheral venous pressure.

PMID- 29047139
TI  - Suxamethonium or rocuronium for rapid sequence induction of anaesthesia?

PMID- 29047140
TI  - Iliac artery balloon catheter use in abnormally invasive placental disease
      management.

PMID- 29047141
TI  - Dawn song in natural and artificial continuous day: Light pollution affects
      songbirds at high latitudes.
AB  - In Focus: Da Silva, A., & Kempenaers, B. (2017). Singing from North to South:
      Latitudinal variation in timing of dawn singing under natural and artificial
      light conditions. Journal of Animal Ecology, 86, 1286-1297. doi: 10.1111/1365
      2656.12739 Satellite images of the world at night show bright dots connected by
      glowing lines crisscrossing the globe. As these connect-the-dots become brighter
      and expand into more and more remote regions, much of the flora and fauna of the
      world are experiencing evolutionarily unprecedented levels of light at night.
      Light cues are essential to most physiological and behavioural processes, and so
      the need to measure the effects of light pollution on these processes is
      critical. In this issue, Da Silva and Kempenaers take on this task using an
      important reproductive behaviour in songbirds-dawn song. The geographic, temporal
      and taxonomic breadth of sampling in this study allows for a close examination of
      a potentially complex interaction between light pollution and natural variation
      in the behaviour of dawn singing across latitude, season and species. Their
      extensive dataset highlights complexity in how songbirds respond to light
      pollution. Although light pollution has a strong effect on the timing of dawn
      song, not all songbirds respond the same way to light pollution, and the effects
      of light pollution vary with changes in natural light levels. Early dawn singers
      show more flexibility in the timing of dawn song across the season and across
      latitudes than late dawn singers, and also appear less affected by light
      pollution at high latitudes than are late dawn singers. These findings suggest
      that not all songbirds are responding to artificial continuous daylight as they
      do to natural continuous daylight, highlighting the general need to measure the
      fitness effects of light pollution.

PMID- 29047142
TI  - Relevance of liver-limited disease in metastatic colorectal cancer: Subgroup
      findings of the FIRE-3/AIO KRK0306 trial.
AB  - In metastatic colorectal cancer (mCRC), liver-limited disease (LLD) is associated
      with a higher chance of metastectomy leading to long-term survival. However,
      limited data describes the prognostic and predictive relevance of initially
      unresectable LLD with regard to targeted first-line therapy. The present analysis
      investigated the relevance of initially unresectable LLD in mCRC patients treated
      with targeted therapy against either the epidermal growth factor receptor (EGFR)
      or vascular epithelial growth factor (VEGF). The analysis was performed based on
      FIRE-3, a randomized phase III trial comparing first-line chemotherapy with
      FOLFIRI plus either cetuximab (anti-EGFR) or bevacizumab (anti-VEGF) in RAS wild
      type (WT) mCRC. Of 400 patients, 133 (33.3%) had LLD and 267 (66.8%) had non-LLD.
      Median overall survival (OS) was significantly longer in LLD compared to non-LLD
      patients (36.0 vs. 25.4 months; hazard ratio [HR] = 0.66; 95% confidence interval
      [CI]: 0.51-0.87; p = 0.002). In a multivariate analysis also including secondary
      hepatic resection as time-dependent variable, LLD status was independently
      prognostic for OS (HR = 0.67; 95% CI: 0.50-0.91; p = 0.01). As assessed by
      interaction tests, treatment benefit from FOLFIRI plus cetuximab compared to
      FOLFIRI plus bevacizumab was independent of LLD status with regard to objective
      response rate (ORR), early tumour shrinkage >=20% (ETS), depth of response (DpR)
      and OS (all p > 0.05). In conclusion, LLD could be identified as a prognostic
      factor in RAS-WT mCRC, which was independent of hepatic resection in patients
      treated with targeted therapy. LLD had no predictive relevance since benefit from
      FOLFIRI plus cetuximab over bevacizumab was independent of LLD status.

PMID- 29047143
TI  - Rising Drug Costs Drives the Growth of Pharmacy Benefit Managers Exclusion Lists:
      Are Exclusion Decisions Value-Based?
AB  - OBJECTIVE: We examine whether drugs' excluded versus recommended status on
      pharmacy benefit manager exclusion lists corresponds to evidence from cost
      effectiveness analyses, lack of evidence, or rebates. DATA SOURCES: To find cost
      effectiveness data for drugs on 2016 exclusion lists of CVS Caremark and Express
      Scripts, we searched the Tufts Cost-Effectiveness Analysis Registry and the peer
      reviewed literature. STUDY DESIGN: For each excluded and recommended drug, we
      compared the mean cost-per-QALY, and we calculated the difference between the
      numbers of excluded and recommended drugs for which we could find no cost
      effectiveness evidence. DATA COLLECTION: As keywords in our searches, we used the
      brand and generic drug name and "cost-effectiveness" and "cost-per-quality
      adjusted life-year." Of 240 retrieved studies, 110 were selected for analysis.
      PRINCIPAL FINDINGS: The mean cost-per-QALY for excluded drugs was higher
      ($51,611) than the cost-per-QALY for recommended drugs ($49,474), but not
      statistically significant. We could find no cost-effectiveness evidence in the
      Registry or peer-reviewed literature for 23 of the excluded drugs, and no
      evidence for 5 of the recommended drugs. CONCLUSIONS: Cost-effectiveness does not
      correlate with a drug's excluded or recommended status. Lack of cost
      effectiveness evidence favors a drug's excluded status.

PMID- 29047144
TI  - MECOM, HBS1L-MYB, THRB-RARB, JAK2, and TERT polymorphisms defining the genetic
      predisposition to myeloproliferative neoplasms: A study on 939 patients.
AB  - Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis
      (PMF) are classical myeloproliferative neoplasms (MPN), characterized by specific
      somatic mutations in JAK2, CALR or MPL genes. JAK2 46/1 and TERT rs2736100
      polymorphisms are known to significantly predispose to MPN. This study aimed to
      establish the additional contribution of the recently described MECOM rs2201862,
      HBS1L-MYB rs9376092 and THRB-RARB rs4858647 polymorphisms to the occurrence of
      MPN. These three polymorphisms, along with JAK2 46/1 and TERT rs2736100 were
      genotyped in 939 MPN patients (454 with ET, 337 with PV and 148 with PMF) and 483
      controls. MECOM rs2201862 associated significantly with each MPN entity, except
      for ET, and with all major molecular sub-types, especially those CALR-mutated (OR
      = 1.4; 95% CI = 1.1-1.8; P-value = .005). HBS1L-MYB rs9376092 associated only
      with JAK2 V617F-mutated ET (OR = 1.4; 95% CI = 1.1-1.7; P-value = .003). THRB
      RARB rs4858647 had a weak association with PMF only (OR = 1.5; 95% CI = 1-2.1; P
      value = .04). Surprisingly, JAK2 46/1 haplotype was associated significantly not
      only with JAK2 V617F-mutated MPN, but also with CALR-mutated MPN (OR = 1.4; 95%
      CI = 1.1-1.8; P-value = .01). TERT rs2736100 was associated equally strong with
      all MPN, regardless of phenotype or molecular sub-type. In conclusion, JAK2 46/1,
      TERT rs2736100 and MECOM rs2201862 are the chief predisposing polymorphisms to
      MPN.

PMID- 29047145
TI  - A randomized controlled trial comparing two vaso-occlusive episode (VOE)
      protocols in sickle cell disease (SCD).
AB  - Limited evidence guides opioid dosing strategies for acute Sickle Cell (SCD)
      pain. We compared two National Heart, Lung and Blood (NHBLI) recommended opioid
      dosing strategies (weight-based vs. patient-specific) for ED treatment of acute
      vaso-occlusive episodes (VOE). A prospective randomized controlled trial (RCT)
      was conducted in two ED's. Adults >= 21 years of age with SCD disease were
      eligible. Among the 155 eligible patients, 106 consented and 52 had eligible
      visits. Patients were pre-enrolled in the outpatient setting and randomized to
      one of two opioid dosing strategies for a future ED visit. ED providers accessed
      protocols through the electronic medical record. Change in pain score (0-100 mm
      VAS) from arrival to ED disposition, as well as side effects were assessed. 52
      patients (median age was 27 years, 42% were female, and 89% black) had one or
      more ED visits for a VOE (total of 126 ED study visits, up to 5 visits/patient
      were included). Participants randomized to the patient-specific protocol
      experienced a mean reduction in pain score that was 16.6 points greater than
      patients randomized to the weight-based group (mean difference 95% CI = 11.3 to
      21.9, P = 0.03). Naloxone was not required for either protocol and nausea and/or
      vomiting was observed less often in the patient-specific protocol (25.8% vs
      59.4%, P = 0.0001). The hospital admission rate for VOE was lower for patients in
      the patient-specific protocol (40.3% vs 57.8% P = 0.05). NHLBI guideline-based
      analgesia with patient-specific opioid dosing resulted in greater improvements in
      the pain experience compared to a weight-based strategy, without increased side
      effects.

PMID- 29047146
TI  - Incidence and risk factors of colorectal cancer based on 56 324 health checkups:
      A 7-year retrospective cohort study.
AB  - BACKGROUND AND AIM: Although mortality rates of colorectal cancer (CRC) have been
      increasing in Japan, its screening rates remain stagnant at 19.2% among Japanese
      population aged > 40 years in 2014. To evaluate the importance of CRC screening
      by fecal occult blood test (FOBT), this study estimated the incidence of FOBT
      positivity and CRC by sex-age stratification and clarified the risk factors for
      CRC. METHODS: Between 2007 and 2014, 56 324 residents (21 517 men and 34 807
      women) were enrolled in this study. The sex-age-stratified incidence rates of
      FOBT-positivity and CRC were estimated by records from health checkups and
      colonoscopy. Regarding CRC incidence rate in particular, positive predictive
      value was adopted to adjust bias of FOBT-positivity that did not undergo
      colonoscopy by person-year method. To investigate the risks of CRC onset, a
      nested case-control study with 1:10 person-matching on sex and age was performed.
      RESULTS: Incidence rates of FOBT-positivity and CRC are 4183/100 000 person-year
      (100 Kpy) and 141.3/100 Kpy, respectively. In both cases, men has higher
      incidence rate than women (1.3 times for FOBT; 4977 vs 3718/100 Kpy and 2.3 times
      for CRC; 217.0 vs 96.4/100 Kpy). CONCLUSIONS: The records from health checkups
      were useful to estimate incidence rates of CRC with this procedure. The age
      stratified incidence rate indicated the importance of CRC screening by FOBT,
      especially for men and those aged > 50 years. Additionally, it is strongly
      recommended to do further investigation if positive for initial FOBT screening
      especially for those who are > 70 years.

PMID- 29047147
TI  - Case-control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized
      epilepsies.
AB  - Epilepsy is a common complex neurological disorder, and some forms are resistant
      to drug treatment. The HCN1/HCN2 genes encode hyperpolarization-activated cyclic
      nucleotide-gated channels, which play important roles in the electrophysiology of
      neurons. We investigated the association between HCN1/HCN2 variants and drug
      resistance or the risk of genetic generalized epilepsies (GGEs). We used matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry to assess
      nine variants of HCN1/HCN2 in 284 healthy participants and 483 GGEs (279 drug
      responsive, 204 drug-resistant). Frequencies of HCN2 rs7255568 and rs3752158 G
      alleles differed in GGEs and in controls (P = .039, P = .027, respectively). The
      frequency of HCN2 haplotype (CAC) was higher in patients than controls (P =
      .046). The frequency of the HCN1 rs10462087 CC+CT genotype was lower in patients
      with childhood absence epilepsy (CAE) than controls (P = .047). Rs7255568 was
      associated with the risk of CAE (P = .028) and juvenile myoclonic epilepsy (JME)
      (P = .02). Rs3752158 was associated with the risk of generalized tonic-clonic
      seizures, JME, and febrile seizures (all P < .05). The frequency of the HCN2
      haplotype (CAC) was higher in patients with JME (P = .015) and in those with
      febrile seizures (P = .024) than in controls. No significant association was
      found between HCN1/HCN2 alleles, genotypes or haplotypes, and drug resistance in
      patients. After Bonferroni's multiple comparisons correction, only the HCN2
      rs3752158 C allele and GC+CC genotype frequencies in patients with JME were
      higher than those in controls (19.2% vs 11.6%, odds ratio (OR) = 1.71, 95% CI =
      1.18-2.32), P = .004 < 0.05/9; 36% vs 22.2%, OR = 1.62(1.18-2.23), P = .003 <
      0.05/9). Our study suggests that HCN2 rs3752158 is involved in the susceptibility
      to JME.

PMID- 29047148
TI  - Epidemiological survey of patients with psoriasis in Matsumoto city, Nagano
      Prefecture, Japan.
AB  - A local epidemiological survey of psoriasis was conducted from 19 February to 30
      June 2016 in Matsumoto city, Nagano Prefecture, Japan. Patients were
      predominantly male (268 cases, 71.5% males vs 107 cases, 28.5% females). We
      estimated that the prevalence of psoriasis was 0.097% in the Matsumoto area. The
      clinical types of psoriasis identified were psoriasis vulgaris (90.7%), psoriatic
      arthritis (5.9%), pustular psoriasis (2.1%), guttate psoriasis (1.0%) and
      psoriatic erythroderma (0.3%). The topical therapeutic agents included
      corticosteroids (84.0%), vitamin D3 analogs (61.5%), and a combination of
      calcipotriol and betamethasone dipropionate (31.0%). Current systemic treatments
      included cyclosporin (9.0%), etretinate (7.4%) and methotrexate (1.3%). Biologic
      treatments included adalimumab (4.0%), ustekinumab (2.7%), infliximab (1.3%) and
      secukinumab (0.8%). Ultraviolet B therapy (11.3%) was the predominant
      phototherapy in which narrow band ultraviolet B therapy accounted for the
      majority, followed by psoralen and ultraviolet A therapy (1.0%). According to the
      recent evolution of psoriasis treatment, the use of biologics has been
      increasing. This study demonstrates the changes of treatment trends of psoriasis
      in a non-metropolitan regional area.

PMID- 29047149
TI  - Cognitive and physical development in HIV-positive children in South Africa and
      Malawi: A community-based follow-up comparison study.
AB  - BACKGROUND: Child development is negatively impacted by HIV with children that
      are infected and affected by HIV performing worse than their peers in cognitive
      assessments. METHODS: We conducted a descriptive follow-up comparison study
      (n=989) in South Africa and Malawi. We tracked child development in 135 HIV
      positive children compared to 854 uninfected children aged 4-13 years attending
      community-based organizations at baseline and again 12-15 months later. RESULTS:
      Children with HIV were more often stunted (58.8% vs. 27.4%) and underweight
      (18.7% vs. 7.1%). They also had significantly poorer general physical functioning
      (M=93.37 vs. M=97.00). HIV-positive children scored significantly lower on digit
      span and the draw-a-person task. CONCLUSIONS: These data clearly show that HIV
      infection poses a serious risk for child development and that there is a need for
      scaled up interventions. Community-based services may be ideally placed to
      accommodate such provision and deliver urgently needed support to these children.

PMID- 29047151
TI  - Acute immune toxicity during anti-thymocyte globulin: That's CARPA!

PMID- 29047150
TI  - Rebamipide alleviates radiation-induced colitis through improvement of goblet
      cell differentiation in mice.
AB  - BACKGROUND AND AIM: Radiation-induced colitis is a common clinical problem
      associated with radiotherapy and accidental exposure to ionizing radiation.
      Goblet cells play a pivotal role in the intestinal barrier against pathogenic
      bacteria. Rebamipide, an anti-gastric ulcer drug, has the effects to promote
      goblet cell proliferation. The aim of this study was to investigate whether
      radiation-induced colonic injury could be alleviated by rebamipide. METHODS: This
      study orally administered rebamipide for 6 days to mice, which were subjected to
      13 Gy abdominal irradiation, to evaluate the therapeutic effects of rebamipide
      against radiation-induced colitis. To confirm the effects of rebamipide on
      irradiated colonic epithelial cells, this study used the HT29 cell line. RESULTS:
      Rebamipide clearly alleviated the acute radiation-induced colitis, as reflected
      by the histopathological data, and significantly increased the number of goblet
      cells. The drug also inhibited intestinal inflammation and protected from
      bacterial translocation during acute radiation-induced colitis. Furthermore,
      rebamipide significantly increased mucin 2 expression in both the irradiated
      mouse colon and human colonic epithelial cells. Additionally, rebamipide
      accelerated not only the recovery of defective tight junctions but also the
      differentiation of impaired goblet cells in an irradiated colonic epithelium,
      which indicates that rebamipide has beneficial effects on the colon. CONCLUSIONS:
      Rebamipide is a therapeutic candidate for radiation-induced colitis, owing to its
      ability to inhibit inflammation and protect the colonic epithelial barrier.

PMID- 29047152
TI  - False gold: Safely navigating open access publishing to avoid predatory
      publishers and journals.
AB  - AIM: The aim of this study was to review and discuss predatory open access
      publishing in the context of nursing and midwifery and develop a set of
      guidelines that serve as a framework to help clinicians, educators and
      researchers avoid predatory publishers. BACKGROUND: Open access publishing is
      increasingly common across all academic disciplines. However, this publishing
      model is vulnerable to exploitation by predatory publishers, posing a threat to
      nursing and midwifery scholarship and practice. Guidelines are needed to help
      researchers recognize predatory journals and publishers and understand the
      negative consequences of publishing in them. DESIGN: Discussion paper. DATA
      SOURCES: A literature search of BioMed Central, CINAHL, MEDLINE with Full Text
      and PubMed for terms related to predatory publishing, published in the period
      2007-2017. IMPLICATIONS FOR NURSING: Lack of awareness of the risks and pressure
      to publish in international journals, may result in nursing and midwifery
      researchers publishing their work in dubious open access journals. Caution should
      be taken prior to writing and submitting a paper, to avoid predatory publishers.
      FINDINGS: The advantage of open access publishing is that it provides readers
      with access to peer-reviewed research as soon as it is published online. However,
      predatory publishers use deceptive methods to exploit open access publishing for
      their own profit. Clear guidelines are needed to help researchers navigate safely
      open access publishing. CONCLUSION: A deeper understanding of the risks of
      predatory publishing is needed. Clear guidelines should be followed by nursing
      and midwifery researchers seeking to publish their work in open access journals.

PMID- 29047153
TI  - Structured nurse-led follow-up for patients after discharge from the intensive
      care unit: Prospective quasi-experimental study.
AB  - AIMS: The aim of this study was to describe a structured 3-month nurse-led follow
      up of patients after discharge from intensive care and measure its effects on
      health status. BACKGROUND: Patients requiring intensive care stay frequently have
      lengthy and incomplete recovery suggesting need for additional support. The
      effects of intensive care nurse-led follow-up have not been sufficiently
      elucidated. DESIGN: A prospective, quasi-experimental study of patients who
      received structured nurse-led follow-up from intensive care nurses after
      discharge from intensive care until 3 months afterwards. The control group
      received usual care. METHODS: Of 574 patients assessed for eligibility, from
      November 2012 - May 2015, 168 were assigned to the experimental group (N = 73)
      and the control group (N = 75). Primary outcome was health status, measured with
      eight scales of Short Form-36v2, before the intensive care admission and at four
      time points until 12 months after intensive care. A mixed effect model tested
      differences between the groups over time. Criteria for Reporting Development and
      Evaluation of Complex Interventions 2 guideline, guided the reporting of the
      intervention. RESULTS: The structured nurse-led follow-up did not improve
      patients' health status compared with usual care (mixed effect model, p = .078
      .937). CONCLUSION: The structured nurse-led follow-up did not reveal an effect on
      the intensive care patients studied. Further examination of intensive care nurse
      led follow-up is needed, taking into account the heterogeneity of the patient
      population, variations in length of ward stay, patients' health care needs during
      the first week at home after discharge from general ward and health status before
      intensive care admission.

PMID- 29047154
TI  - Effects of testosterone enanthate and resistance training on myocardium in Wistar
      rats; clinical and anatomical pathology.
AB  - This study was performed to determine the effects of 8 weeks testosterone
      enanthate (TE) injection and resistance training (RT) on cardiac muscle in male
      Wistar rats. A total of 28 male adult Wistar rats were randomly divided into 4
      groups; control + placebo, RT + placebo, TE and TE + RT. Testosterone enanthate
      (20 mg/kg BW, IM) and placebo (olive oil; 0.2 ml, IM) were injected twice a week
      for 2 months. The RT consisted of climbing (5 reps/3 sets) a ladder carrying a
      load suspended from the tail. The serum activities of aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine
      kinase MB (CK-MB) and serum level of creatinine, urea and cardiac troponin I
      (CTnI) were evaluated. After sacrifice, samples from myocardial muscle were
      collected for histopathology evaluation. The serum concentration of CTnI and CK
      MB activity significantly increased in group RT compared with control (p < .05).
      In group RT + TE, all biomarkers of muscle damage (CTnI, CK-MB, AST, LDH) were
      significantly more than those in control (p < .05). Also, mild myocardial
      hypertrophy was observed in RT and RT + TE groups. The higher level of all heart
      damage biomarkers in the RT + TE group rather than control may indicate the
      synergistic effects of medication and exercise.

PMID- 29047155
TI  - Maduramicin induces apoptosis and necrosis, and blocks autophagic flux in
      myocardial H9c2 cells.
AB  - Maduramicin, a polyether ionophore antibiotic, is widely used as an anticoccidial
      agent in the poultry industry. It has been reported that maduramicin may cause
      heart and skeletal muscle cell damage, resulting in heart failure, skeletal
      muscle degeneration and even death in animals and humans, if improperly used.
      However, the molecular mechanism behind its capability to cause death of cardiac
      cells is not known. Here, we show that maduramicin induced apoptosis and necrosis
      in rat myocardial cells (H9c2). Maduramicin did not apparently upregulate the
      expression of pro-apoptotic proteins (e.g., BAD, BAK and BAX) or downregulate the
      expression of anti-apoptotic proteins (e.g. Bcl-2, Bcl-xL, Mcl-1 and survivin).
      Interestingly, maduramicin increased the expression of DR4 and TRAIL, activating
      caspases 8/3 and triggering cleavage of poly ADP ribose polymerase (PARP). In
      addition, maduramicin induced nuclear translocation of apoptosis inducing factor.
      Furthermore, maduramicin blocked autophagic flux, as evidenced by inducing
      accumulation of both LC3-II and p62/SQSTM1. Taken together, the above results
      suggest that maduramicin executes its toxicity in the myocardial cells at least
      by inducing caspase-dependent cell death through TRAIL/DR4-mediated extrinsic
      pathway and caspase-independent cell death by inducing apoptosis inducing factor
      nuclear translocation and blocking autophagic flux. Our findings provide a new
      insight into the molecular mechanism of maduramicin's toxicity in myocardial
      cells.

PMID- 29047156
TI  - Cyclophosphamide-induced male subfertility in mice: An assessment of the
      potential benefits of Maca supplement.
AB  - Effects of Lepidium meyenii (Maca) on cyclophosphamide (CYP)-induced gonadal
      toxicity in male mice were investigated. Mice were assigned to six treatment
      groups: Vehicle control, CYP control, CYP plus oral Maca (500 or 1,000 mg/kg),
      and oral Maca (500 or 1,000 mg/kg). CYP was administered via the intraperitoneal
      route (days 1-2), while vehicle or Maca were administered daily for 28 days. On
      day 28, half of the animals in each group were either sacrificed or paired with
      age-matched females for fertility assessment. Plasma testosterone assay, sperm
      analysis and assessment of tissue antioxidant/morphological status were also
      carried out. CYP administration was associated with oxidative stress,
      subfertility and morphometric/morphological indices of gonadal injury, while
      administration of Maca mitigated CYP-induced gonadal toxicity and subfertility.
      This study shows that Maca is beneficial in the mitigation of CYP-induced male
      gonadal insufficiency and/or testicular morphological changes; however, further
      studies will be needed to ascertain its usability for this purpose in humans.

PMID- 29047157
TI  - Protein contact prediction by integrating deep multiple sequence alignments,
      coevolution and machine learning.
AB  - In this study, we report the evaluation of the residue-residue contacts predicted
      by our three different methods in the CASP12 experiment, focusing on studying the
      impact of multiple sequence alignment, residue coevolution, and machine learning
      on contact prediction. The first method (MULTICOM-NOVEL) uses only traditional
      features (sequence profile, secondary structure, and solvent accessibility) with
      deep learning to predict contacts and serves as a baseline. The second method
      (MULTICOM-CONSTRUCT) uses our new alignment algorithm to generate deep multiple
      sequence alignment to derive coevolution-based features, which are integrated by
      a neural network method to predict contacts. The third method (MULTICOM-CLUSTER)
      is a consensus combination of the predictions of the first two methods. We
      evaluated our methods on 94 CASP12 domains. On a subset of 38 free-modeling
      domains, our methods achieved an average precision of up to 41.7% for top L/5
      long-range contact predictions. The comparison of the three methods shows that
      the quality and effective depth of multiple sequence alignments, coevolution
      based features, and machine learning integration of coevolution-based features
      and traditional features drive the quality of predicted protein contacts. On the
      full CASP12 dataset, the coevolution-based features alone can improve the average
      precision from 28.4% to 41.6%, and the machine learning integration of all the
      features further raises the precision to 56.3%, when top L/5 predicted long-range
      contacts are evaluated. And the correlation between the precision of contact
      prediction and the logarithm of the number of effective sequences in alignments
      is 0.66.

PMID- 29047159
TI  - Pigmentary mosaicism with trisomy 7.

PMID- 29047158
TI  - Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic
      leukemia and T-lymphoblastic lymphoma.
AB  - Nelarabine, a water soluble prodrug of 9-beta-D-arabinofuranosylguanine (ara-G),
      is a T-cell specific purine nucleoside analogue. Given its activity in relapsed
      and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic
      lymphoma (T-LBL), we sought to define its role in the frontline treatment of
      adult patients. Therefore, we conducted a single arm phase 2 study to determine
      the safety and efficacy of nelarabine in combination with hyper-CVAD in newly
      diagnosed patients. For induction/consolidation, patients received eight cycles
      of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two
      cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days.
      This was followed by thirty months of POMP maintenance chemotherapy with two
      additional cycles of nelarabine given instead of cycles 6 and 7 of POMP
      maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL,
      were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100%
      respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients.
      There were 21 relapses (31%) including 2 after allogeneic stem cell
      transplantation. Median duration of follow-up was 42.5 months. The 3-year
      complete remission duration (CRD) and overall survival (OS) rates were 66% and
      65%, respectively. Compared to our historic hyper-CVAD data, there was no
      survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus
      nelarabine was well tolerated and active in the frontline treatment of adult T
      ALL/LBL patients.

PMID- 29047160
TI  - Mutations in the genes for keratin-4 and keratin-13 in Swedish patients with
      white sponge nevus.
AB  - BACKGROUND: White sponge nevus is a rare autosomal dominant disorder that affects
      the non-keratinised stratified squamous epithelium. Mutations in the genes that
      encode mucosa-specific keratin-4 and keratin-13 are strongly linked to the
      manifestation of white sponge nevus. This study involved mutational analysis of
      the genes encoding keratin-4 and keratin-13 in two Swedish families with white
      sponge nevus. METHODS: The diagnosis of white sponge nevus was based on disease
      history, clinical characteristics of the lesions and, in the majority of the
      cases, histopathological examination. Samples were collected from the affected
      buccal mucosa using buccal swabs. DNA was subsequently extracted and amplified
      using touchdown-PCR. The keratin-4 and keratin-13 genes were sequenced, and a
      genetic analysis was performed. RESULTS: A novel heterozygous missense mutation
      was identified in exon 1A of the keratin-4 gene in Family 2. In addition,
      previously reported heterozygous missense mutations were identified in the
      keratin-4 (E449K, A72V, Q156R, R208H) and keratin-13 (L115P) genes in both
      families. CONCLUSION: We describe a novel heterozygous missense mutation in the
      keratin-4 gene of a Swedish family with white sponge nevus. Our results support
      the notion that mutations in keratin-4 and keratin-13 are the underlying cause of
      white sponge nevus.

PMID- 29047161
TI  - Donor lymphocyte infusion and methotrexate for immune recovery after T-cell
      depleted haploidentical transplantation.
AB  - CD34+ cell selection minimizes graft-versus-host disease (GVHD) after
      haploidentical donor stem cell transplant but is associated with slow immune
      recovery and infections. We report a Phase I/II study of prophylactic donor
      lymphocyte infusion (DLI) followed by methotrexate (MTX) GVHD prophylaxis after
      CD34-selected haploidentical donor transplant. A prophylactic DLI was given
      between day +30 and +42. Rituximab was given with DLI for the last 10 patients.
      The goal of the study was to determine a DLI dose that would result in a CD4+
      cell count > 100/uL at Day +120 in >= 66% of patients with <= 33% grade II-III,
      <= 17% grade III, and no grade IV acute GVHD by Day +180. Thirty-five patients
      with malignant (n = 25) or nonmalignant disease (n = 10) were treated after CD34
      selected haploidentical donor peripheral blood stem cell transplant. The DLI dose
      of 5 * 104 /kg met the CD4/GVHD goal with 67% of patients having CD4+ cells >
      100/uL and 11% grade II-IV acute GVHD. The cumulative incidence of chronic GVHD
      was 16%. Fatal viral and fungal infections occurred in 11%. The 2 year estimated
      overall survival was 69% and the relapse rate was 14% for patients in remission
      at transplant. There was no effect of NK alloreactivity on relapse. Nine of ten
      patients at the target DLI dose cohort of 5 * 104 /kg are alive with median
      follow-up of 18 mos (range 6-29). Delayed prophylactic DLI and MTX was associated
      with promising outcomes at the target DLI dose. This trial was registered at
      clinicaltrials.gov, # NCT01027702.

PMID- 29047162
TI  - Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation-induced
      apoptosis and oxidative stress through activation of mitochondrial aldehyde
      dehydrogenase 2.
AB  - Baicalin, a flavonoid glycoside separated from Scutellaria baicalensis, has
      cardioprotection against ischaemia/reperfusion (I/R) injury. Mitochondrial
      aldehyde dehydrogenase 2 (ALDH2) is considered as an endogenous protective
      mechanism against I/R injury depending on its anti-oxidant and anti-apoptotic
      characteristics. The present study demonstrates whether ALDH2 contributes to the
      cardioprotection of baicalin against hypoxia/reoxygenation (H/R)-inudced H9c2
      cardiomyocytes injury. Our results observed that H/R treatment resulted in a
      significant decrease in cells viability and obvious increases in caspase-3
      activity and apoptosis rate in H9c2 cells, while these alterations were evidently
      reversed by baicalin pretreatment. Simultaneously, baicalin mitigated H/R-induced
      the decreases in the levels of ALDH2 mRNA and protein as well as the activity of
      ALDH2 in H9c2 cells. However, we found that daidzin, an ALDH2 antagonist,
      remarkably attenuated baicalin-elicited inhibitory action on H/R-induced the
      downregulation of cells viability and Bcl-2 protein expression, and the
      upregulations of caspase-3 activity, apoptosis rate, cytochrome c and Bax
      proteins expressions in H9c2 cells. In addition, baicalin reversed H/R-induced
      oxidative stress as evidenced by the downregulation of malondialdehyde (MAD) and
      4-hydroxy aldehydes (4-HNE) levels, the inhibition of endogenous reactive oxygen
      species (ROS) generation, and the downregulation of superoxide dismutase (SOD)
      activity induced by H/R treatment, while these effects were also blocked by
      daidzin. Furthermore, we found that Alda-1, an ALDH2 agonist, also abolished H/R
      induced cytotoxicity, apoptosis, and oxidative stress, indicating that ALDH2
      mediated H/R-induced H9c2 cell injury. Overall, these results suggested that
      baicalin prevents H/R-induced apoptosis and oxidative stress through enhancing
      ALDH activity and expression in H9c2 cardiomyocytes.

PMID- 29047163
TI  - From job stress to intention to leave among hospital nurses: A structural
      equation modelling approach.
AB  - AIMS: The aim of this study was to examine the structural relationships linking
      job stress to leaving intentions through job satisfaction, depressed mood and
      stress adaptation among hospital nurses. BACKGROUND: High turnover among nurses
      is a global concern. Structural relationships linking job stress to leaving
      intentions have not been thoroughly examined. DESIGN: Two nationwide cross
      sectional surveys of full-time hospital staff in 2011 and 2014. METHODS: The
      study participants were 26,945 and 19,386 full-time clinical nurses in 2011 and
      2014 respectively. Structural equation modelling was used to examine the
      interrelationships among the study variables based on the hypothesized model. We
      used cross-validation procedures to ensure the stability and validity of the
      model in the two samples. RESULTS: There were five main paths from job stress to
      intention to leave the hospital. In addition to the direct path, job stress
      directly affected job satisfaction and depressed mood, which in turn affected
      intention to leave the hospital. Stress adaptation mitigated the effects of job
      stress on job satisfaction and depressed mood, which led to intention to leave
      the hospital. Intention to leave the hospital preceded intention to leave the
      profession. Those variables explained about 55% of the variance in intention to
      leave the profession in both years. CONCLUSION: The model fit was good for both
      samples, suggesting validity of the model. Strategies to decrease turnover
      intentions among nurses could focus on creating a less stressful work
      environment, increasing job satisfaction and stress adaptation and decreasing
      depressed mood. Hospitals should cooperate in this issue to decrease nurse
      turnover.

PMID- 29047164
TI  - Multifocal fixed drug eruption to ceftazidime in a child with cystic fibrosis.

PMID- 29047166
TI  - Pre-Assembled Coumarin-Rhodamine Scaffold for Ratiometric Sensing of Nitric Oxide
      and Hypochlorite.
AB  - A new pre-assembled ratiometric sensing platform was constructed from a coumarin
      donor and a rhodamine acceptor designed for through-bond energy transfer (TBET).
      A phenylacetylene linker was installed to disrupt the planarity of the extended
      conjugated system but retaining the efficient energy transfer between the donor
      and acceptor motifs. To demonstrate its versatility as a sensing platform, we
      conjugated recognition motifs through amide coupling reactions to yield two TBET
      chemosensors capable of sensing either endogenously produced NO and ClO- . Both
      probes possessed high selectivity for their analytes, exhibited good stability
      under physiological conditions, and performed well as bioimaging probes in living
      cells.

PMID- 29047165
TI  - OPUS-CSF: A C-atom-based scoring function for ranking protein structural models.
AB  - We report a C-atom-based scoring function, named OPUS-CSF, for ranking protein
      structural models. Rather than using traditional Boltzmann formula, we built a
      scoring function (CSF score) based on the native distributions (derived from the
      entire PDB) of coordinate components of mainchain C (carbonyl) atoms on selected
      residues of peptide segments of 5, 7, 9, and 11 residues in length. In testing
      OPUS-CSF on decoy recognition, it maximally recognized 257 native structures out
      of 278 targets in 11 commonly used decoy sets, significantly outperforming other
      popular all-atom empirical potentials. The average correlation coefficient with
      TM-score was also comparable with those of other potentials. OPUS-CSF is a highly
      coarse-grained scoring function, which only requires input of partial mainchain
      information, and very fast. Thus, it is suitable for applications at early stage
      of structural building.

PMID- 29047168
TI  - Changes in sleep quality with age-a 36-year follow-up study of Finnish working
      aged adults.
AB  - Long-term follow-up data on changes in sleep quality among middle-aged adults is
      scarce. We assessed sleep quality in a population-based cohort (n = 4847) of
      twins born between 1945 and 1957 during a follow-up of 36 years, with four
      measurement points in 1975, 1981, 1990 and 2011. Sleep quality was categorized as
      sleeping well, fairly well, fairly poorly or poorly. The mean age at the
      beginning of follow-up was 24.0, and at the end was 60.3 years. Of all the
      adults, 71.1% slept well or fairly well at each time-point throughout the follow
      up and 0.5% poorly or fairly poorly. The proportion of those sleeping poorly or
      fairly poorly increased linearly over time; 3.5% among both sexes at the start,
      and 15.5% among men and 20.9% among women at the end of the follow-up. The last
      survey indicated a strong association between self-rated health and sleep
      quality: sleeping poorly or fairly poorly was reported 15 times more frequently
      by those rating their health as fairly poor than by those rating their health as
      very good. There was a strong association between indicators of depression and
      poor sleep. Although many studies have reported increasing frequencies in sleep
      problems, our results, based on a long-term cohort study, indicate that the
      majority of people sleep well or fairly well. Sleep quality declines with age,
      but only a very small fraction of the adults in this long follow-up consistently
      slept poorly.

PMID- 29047167
TI  - The association between a genetic risk score for allergy and the risk of
      developing allergies in childhood-Results of the WHISTLER cohort.
AB  - BACKGROUND: Several genetic variants have been associated with the susceptibility
      to allergic disease in adults, but it remains unclear whether these genetic
      variants are also associated with the onset of allergic disease early in life.
      The aim of this study was to develop a genetic risk score (GRS) for allergy based
      on findings in adults and study its predictive capacity for allergy in children.
      METHODS: A GRS was constructed based on 10 SNPs previously associated with
      allergies in adults. The GRS was tested in children who participated in a
      population-based newborn cohort (WHISTLER) and were followed from birth to school
      age. Logistic regression analysis was used to study the association between the
      GRS and the parental-reported allergies at age 5 (based on a reported allergy to
      >=1 of the following allergens: pollen, house dust mites, or pets). A Cox
      regression model was used to study the association between GRS and a physician
      diagnosed allergy during follow-up (allergic conjunctivitis, allergic rhinitis,
      and eczema/dermatitis). Cohen's kappa coefficient was calculated to study the
      agreement between physician-diagnosed allergy and parental-reported allergy at
      age 5. RESULTS: The GRS was significantly associated with parental-reported
      allergy (odds ratio: 15.9, 95% confidence interval (CI): 1.07-233.73) at age 5,
      as well as with a physician-diagnosed allergy during follow-up (hazard ratio:
      1.89, 95% CI: 1.05-3.41). The overall agreement between physician-diagnosed and
      parental-reported allergies was 70.5% (kappa: 0.10, 95% CI: 0.03-0.18).
      CONCLUSIONS: An adult-derived GRS for allergy predicts the risk of developing
      allergies in childhood.

PMID- 29047169
TI  - Non-immediate-reading skin tests and prolonged challenges in non-immediate
      hypersensitivity to beta-lactams in children.
AB  - BACKGROUND: A minority of children reporting non-immediate reactions to beta
      lactams (BLs) are allergic. Allergy workup usually includes late-reading (48-72
      hours) skin tests (ST) and short (1-3 days) drug provocation tests (DPT),
      regardless of the chronology of the index reaction. The sensitivity of hyper-late
      reading (>=6-7 days) ST and of prolonged DPT for the diagnosis of non-immediate
      hypersensitivity to BLs is yet to be determined. OBJECTIVES: To establish the
      diagnostic values of late-reading ST and hyper-late-reading ST and of prolonged
      DPT in children reporting non-immediate reactions to BLs. METHODS: Prospective
      assessment of children reporting non-immediate reactions to BLs with late- and
      additional hyper-late-reading intradermal (ID) and patch tests, and if negative,
      with prolonged DPT. RESULTS: Five hundred and fifty children reporting reactions
      to a single or several BLs (674 suspected BLs) were included. Non-immediate
      hypersensitivity to BLs was diagnosed in 63 children (11.5%), reporting 66
      reactions (9.8%), based on responses in ST (n = 17, 25.8%: 5 to ID, 8 to patch
      tests, and 4 to both tests), DPT (n = 43, 65.2%), and clinical history (n = 6,
      9.1%), including 3/9 children with severe cutaneous adverse reactions. Skin test
      positivity was observed after the 6-7th day in 14/17 children, and DPT positivity
      after a median time of 3 days. No severe reaction was observed after ST or during
      prolonged DPT. CONCLUSION: Additional hyper-late-reading of ST enhanced their
      positivity. However, their overall sensitivity remained weak, especially in non
      severe cases. Prolonged DPT are safe and may improve the performance of DPT in
      the diagnosis of non-immediate hypersensitivity to BLs.

PMID- 29047170
TI  - IRF-1 SNPs influence the risk for childhood allergic asthma: A critical role for
      pro-inflammatory immune regulation.
AB  - BACKGROUND: Allergic and non-allergic childhood asthma has been characterized by
      distinct immune mechanisms. While interferon regulating factor 1 (IRF-1)
      polymorphisms (SNPs) influence atopy risk, the effect of SNPs on asthma phenotype
      specific immune mechanisms is unclear. We assessed whether IRF-1 SNPs modify
      distinct immune-regulatory pathways in allergic and non-allergic childhood asthma
      (AA/NA). METHODS: In the CLARA study, asthma was characterized by doctor's
      diagnosis and AA vs NA by positive or negative specific IgE. Children were
      genotyped for four tagging SNPs within IRF-1 (n = 172). mRNA expression was
      measured with qRT-PCR. Gene expression was analyzed depending on genetic variants
      within IRF-1 and phenotype including haplotype estimation and an allelic risk
      score. RESULTS: Carrying the risk alleles of IRF-1 in rs10035166, rs2706384, or
      rs2070721 was associated with increased risk for AA. Carrying the non-risk allele
      in rs17622656 was associated with lower risk for AA but not NA. In AA carrying
      the risk alleles, an increased pro-inflammatory expression of ICAM3, IRF-8, XBP
      1, IFN-gamma, RGS13, RORC, and TSC2 was observed. NOD2 expression was decreased
      in AA with risk alleles in rs2706384 and rs10035166 and with risk haplotype.
      Further, AA with risk haplotype showed increased IL-13 secretion. NA with risk
      allele in rs2070721 compared to non-risk allele in rs17622656 showed
      significantly upregulated calcium, innate, mTOR, neutrophil, and inflammatory
      associated genes. CONCLUSION: IRF-1 polymorphisms influence the risk for
      childhood allergic asthma being associated with increased pro-inflammatory gene
      regulation. Thus, it is critical to implement IRF-1 genetics in immune assessment
      for childhood asthma phenotypes.

PMID- 29047171
TI  - Effectiveness and side-effect profile of stimulant therapy as monotherapy and in
      combination in the central hypersomnias in clinical practice.
AB  - Effectiveness and side-effect profile data on pharmacotherapy for daytime
      sleepiness in central hypersomnias are based largely upon randomized controlled
      trials. Evidence regarding the use of combination therapy is scant. The aim of
      this study was to examine the effectiveness and occurrence of drug-related side
      effects of these drugs in routine clinical practice. Adult patients diagnosed
      with a central hypersomnia during a 54-month period at a tertiary sleep disorders
      centre were identified retrospectively. Side effects were recorded at every
      follow-up visit. A total of 126 patients, with 3275 patient-months of drug
      exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n
      = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used
      as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per
      cent of the patients demonstrated a complete, 25% partial and 36% a poor response
      to treatment. Combination treatment improved daytime sleepiness in 55% of the
      patients with residual symptoms despite monotherapy. Sixty per cent of patients
      reported side effects, and 30% reported treatment-limiting side effects. Drugs
      had similar side-effect incidence (P = 0.363) and their side-effect profile met
      those reported in the literature. Twenty-seven per cent of the patients received
      combination treatment and had fewer side effects compared to monotherapy (29.4%
      versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory
      symptom control in most patients with central hypersomnia, but significant side
      effects are common. Combination therapy appears to be a useful and safe option in
      patients with refractory symptoms.

PMID- 29047172
TI  - Fatal anaphylaxis in children in France: Analysis of national data.

PMID- 29047173
TI  - Motivational orientations and performance in penalty throws during elite male
      team handball games.
AB  - This study is based on Regulatory Focus Theory and investigates the links between
      the subjects' motivational orientations for promotion or prevention and their
      performance in handball penalty throws. In a real-world setting with high stakes,
      we analyzed 327 penalties taken from 68 closed games. The results of the 7-meter
      throws constitute the dependent variable (Goal vs Miss). The independent
      variables are the situational focus ([critical moment (ie, final minute) =
      pressure] vs [non-critical moment = no pressure]), the reward structure (ie,
      [thrower's team is behind = losses reward structure] vs [thrower's team is ahead
      or teams are tied = gains reward structure), and the game location (home vs
      away). Using logistic regression analysis, the results show that when there is a
      fit between the situational focus and the reward structure, the thrower's
      performance is higher than when there is a mismatch (OR = 2.21; P = .004). In the
      same way, the thrower's performance is higher when there is high fit between the
      situational focus and the reward structure (OR = 1.78), than when there is a high
      mismatch (OR = 0.54). These results globally support the Regulatory Fit Theory in
      an ecological context.

PMID- 29047174
TI  - Pediatric allergy and immunology in China.
AB  - Over the past 30 years, China has enjoyed rapid economic development along with
      urbanization at a massive scale that the world has not experienced before. Such
      development has also been associated with a rapid rise in the prevalence of
      allergic disorders. Because of the large childhood population in the country, the
      burden of childhood allergic disorders has become one of the major challenges in
      the healthcare system. Among the Chinese centers participating in the
      International Study of Asthma and Allergies in Childhood, the data clearly showed
      a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic
      eczema. However, the discipline of pediatric allergy in mainland China is still
      in its infancy due to the lack of formal training program and subspecialty
      certification. Clinicians and researchers are increasingly interested in
      providing better care for patients with allergies by establishing pediatric
      allergy centers in different regions of the country. Many of them have also
      participated in national or international collaborative projects hoping to answer
      the various research questions related to the discipline of pediatric allergy and
      immunology. It is our hope that the research findings from China will not only
      improve the quality of care of affected children within this country but also the
      millions of patients with allergies worldwide.

PMID- 29047175
TI  - New Generation Agent Defeat Weapons: Energetic N,N'-Ethylene-Bridged
      Polyiodoazoles.
AB  - Sodium salts of iodine-rich pyrazole and imidazole with 1-(2-bromoethyl)-5
      aminotetrazole are useful precursors for energetic N,N'-ethylene-bridged
      polyiodoazoles. Compounds 1-3 were characterized with IR, and 1 H and 13 C NMR
      spectroscopy as well as elemental analyses. The molecular structures of 1 and 2
      were confirmed by using single crystal X-ray diffraction. Heats of formation were
      calculated using Gaussian 03 and detonation properties and biocidal efficiency
      were calculated with CHEETAH 7. The decomposition products of 1-3 destroy
      microbes more effectively than some previously reported biocides since the
      thermal decomposition occurs at below 400  degrees C without addition of oxidizer
      or combustion adjuvant.

PMID- 29047176
TI  - Increase in atopic sensitization rate among Dutch children with symptoms of
      allergic disease between 1994 and 2014.
AB  - BACKGROUND: The prevalence of symptoms of allergic diseases has increased
      significantly during the last decades. However, studies into time trends of
      atopic sensitization among children are limited and have focused on aeroallergen
      sensitization. We aimed to investigate time trends in the prevalence and degree
      of atopic sensitization to inhalant and food allergens among children (0-17
      years) with symptoms of allergic disease. METHODS: Sensitization data of all
      children tested in our clinical laboratory during 1994-2014 were analyzed.
      Sensitization was detected using the ImmunoCAP system and defined as a specific
      IgE level of >=0.35 kU/L. Trends in sensitization rates to 5 food and 5
      aeroallergens for different age categories were investigated with logistic
      regression, adjusted for age and sex. RESULTS: Sensitization data of 18 199
      children were analyzed. Between 1994 and 2014, a steady and statistically
      significant increase in overall sensitization rate was found (from 40.5% in 1994
      to 48.9% in 2014, adjusted odds ratio [aOR] 1.01 per year, 95% confidence
      interval [CI] 1.00 to 1.01, P = .003). This increase in sensitization rate was
      mainly explained by increasing aeroallergen sensitization among 4- to 11-year-old
      children (aOR 1.02, 95% CI 1.01 to 1.02, P < .001). We found no increase in
      sensitization rates to food and aeroallergens in other age categories. The degree
      of sensitization did not change significantly during the study period (all tests
      P > .15). CONCLUSION: We observed a statistically significant increase in
      sensitization rate between 1994 and 2014 among children with symptoms of allergic
      disease. This was mainly explained by increasing aeroallergen sensitization among
      4- to 11-year-olds.

PMID- 29047177
TI  - Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal
      applications, animal models, and possible mechanism of actions.
AB  - Insight into the hepatoprotective effects of medicinally important plants is
      important, both for physicians and researchers. Main reasons for the use of
      herbal medicine include their lesser cost compared with conventional drugs,
      lesser undesirable drug reactions and thus high safety, and reduced side effects.
      The present review focuses on the composition, pharmacology, and results of
      experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn.,
      Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza
      Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium
      intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba
      (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis
      (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis
      (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of
      these plants include immunomodulation, stimulation of hepatic DNA synthesis,
      simulation of superoxide dismutase and glutathione reductase to inhibit oxidation
      in hepatocytes, reduction of intracellular reactive oxygen species by enhancing
      levels of antioxidants, suppression of ethanol-induced lipid accumulation,
      inhibition of nucleic acid polymerases to downregulate viral mRNA transcription
      and translation, free radical scavenging and reduction of hepatic fibrosis by
      decreasing the levels of transforming growth factor beta-1, and collagen
      synthesis in hepatic cells. However, further research is needed to identify,
      characterize, and standardize the active ingredients, useful compounds, and their
      preparations for the treatment of liver diseases.

PMID- 29047178
TI  - The effect of montelukast on early-life wheezing: A randomized, double-blinded
      placebo-controlled study.
AB  - BACKGROUND: Cysteinyl-leukotrienes are increased in the airways of infants with
      virus-associated wheezing. We aimed to determine the effects of a cysteinyl
      leukotriene-1 receptor antagonist on symptoms during an early-life wheezing
      illness and to investigate the factors that affect the response to this drug.
      METHOD: This placebo-controlled double-blinded randomized controlled trial
      recruited children aged 3-36 months with wheezing illness and randomized to
      active drug or placebo for 56 days. A symptom score diary (SSD) was kept by the
      children's caregivers. RESULTS: One-hundred patients completed the study, and 62
      (30 montelukast and 32 placebo) were analyzed. There were no significant
      differences in the percent of symptom-free days, symptom scores, and the need for
      rescue salbutamol between the two groups. However, the percent of symptom-free
      days within the first week was significantly higher for the montelukast than for
      the placebo group (13.8 +/- 4.1% vs. 5.4 +/- 3.4%; P = 0.028); wheezing score at
      7th day was significantly lower for the montelukast than for the placebo group
      (0.5 +/- 0.1 vs. 1.4 +/- 0.2; P = 0.002). In addition, the number of inhaled
      beta2 -agonist rescue episodes per day during the first week was significantly
      lower for the montelukast compared with the placebo group (12.7 +/- 1.8 vs. 19.2
      +/- 1.6; P = 0.013). Conclusions Our results indicate that montelukast may be
      effective for reducing caregiver-observed wheezing and the need for salbutamol
      during the first week of treatment for early-life wheezing. The impact for
      caregivers and the optimal duration of treatment will need to be explored in
      studies of larger size.

PMID- 29047179
TI  - What about sleep homeostasis in insomnia? Comment on the European guideline for
      the diagnosis and treatment of insomnia.

PMID- 29047180
TI  - Systematic screening of viral entry inhibitors using surface plasmon resonance.
AB  - Viral binding and entry into host cells for various viruses have been studied
      extensively, yielding a detailed understanding of the overall viral entry
      process. As cell entry is an essential and requisite process by which a virus
      initiates infection, it is an attractive target for therapeutic intervention. The
      advantages of targeting viral entry are an extracellular target site, relatively
      easy access for biological interventions, and lower toxicity. Several cell-based
      strategies and biophysical techniques have been used to screen compounds that
      block viral entry. These studies led to the discovery of inhibitors against HIV,
      HCV, influenza, Ebola, and RSV. In recent years, several compounds screened by
      fragment-based drug discovery have been approved as drugs or are in the final
      stages of clinical trials. Among fragment screening technologies, surface plasmon
      resonance has been widely used because it provides accurate information on
      binding kinetics, allows real-time monitoring of ligand-drug interactions,
      requires very small sample amounts to perform analyses, and requires no
      modifications to or labeling of ligands. This review focuses on surface plasmon
      resonance-based schemes for screening viral entry inhibitors.

PMID- 29047181
TI  - A Rotaxane Scaffold for the Construction of Multiporphyrinic Light-Harvesting
      Devices.
AB  - A sophisticated photoactive molecular device has been prepared by combining
      recent concepts for the preparation of multifunctional nanomolecules (click
      chemistry on multifunctional scaffolds) with supramolecular chemistry (self
      assembly to prepare rotaxanes). Specifically, a clickable [2]rotaxane scaffold
      incorporating a free-base porphyrin stopper has been prepared and functionalized
      with ten peripheral Zn(II)-porphyrin moieties. Electrochemical investigations of
      the final compound revealed a peculiar behavior resulting from the intramolecular
      coordination of the Zn(II) porphyrin moieties to 1,2,3-triazole units. Finally,
      steady state investigations of the compound combining Zn(II) and free-base
      porphyrin moieties have shown that this compound is a light-harvesting device
      capable of channeling the light energy from the peripheral Zn(II)-porphyrin
      subunits to the core by singlet-singlet energy transfer.

PMID- 29047182
TI  - Nanoscale Metal-Organic Frameworks Decorated with Graphene Oxide for Magnetic
      Resonance Imaging Guided Photothermal Therapy.
AB  - Imaging-guided photothermal therapy (PTT) provides an attractive way to treat
      cancer. A composite material of a nanoscale metal-organic framework (NMOF) and
      graphene oxide (GO) has been prepared for potential use in tumor-guided PTT with
      magnetic resonance imaging (MRI). The NMOFs containing Fe3+ were prefabricated
      with an octahedral morphology through a solvothermal reaction to offer a strong
      T2 -weighted contrast in MRI. Then the NMOFs were decorated with GO nanosheets,
      which had good photothermal properties. After decoration, zeta-potential
      characterization shows that the aqueous stability of the composite material is
      enhanced, UV/Vis and near-infrared (NIR) spectra confirm that NIR absorption is
      also increased, and photothermal experiments reveal that the composite materials
      express higher photothermal conversion effects and conversion stability. The
      fabricated NMOF/GO shows low cytotoxicity, effective T2 -weighted contrast of
      MRI, and positive PTT behavior for a tumor model in vitro. The performance of the
      composite NMOF/GO for MRI and PTT was also tested upon injection into A549 tumor
      bearing mice. The studies in vivo revealed that the fabricated NMOF/GO was
      efficient in T2 -weighted imaging and ablation of the A549 tumor with low
      cytotoxicity, which implied that the prepared composite contrast agent was a
      potential multifunctional nanotheranostic agent.

PMID- 29047183
TI  - Follow-up of patients with uncertain symptoms during an oral food challenge is
      useful for diagnosis.
AB  - BACKGROUND: Uncertain symptoms often emerge during an oral food challenge (OFC),
      and Open-OFCs with those uncertain mild symptoms are ordinarily regarded as
      positive. Double-blind placebo-controlled food challenges should be conducted to
      determine these associations. Nevertheless, studies regarding the diagnosis of
      uncertain food allergy symptoms are lacking. We examined the diagnostic decision
      for a food allergy based on uncertain symptoms during an Open-OFC. METHODS: We
      conducted an Open-OFC between August 2005 and April 2012 with 2271 cases who
      suspected as allergic to hen's eggs, cow's milk, or wheat. For the primary
      diagnosis, Open-OFCs with obvious symptoms were classified as "positive," no
      symptoms as "negative," and uncertain, indeterminate symptoms as "uncertain." We
      encouraged the children in the uncertain group to consume the causative foods at
      home more than twice; if any definitive symptoms were induced, children were
      classified as "intolerant," and children without any symptoms were classified as
      "tolerant," for the final diagnosis. RESULTS: We analyzed 454 uncertain cases
      excluding 781 positive cases and 1036 negative cases. The symptoms that occurred
      for the uncertain cases included slight abdominal pain, localized skin rash, and
      an isolated cough. Of these cases, 362 (79.7%) were considered tolerant at the
      final diagnosis. Of the intolerant children at the final diagnosis, the induced
      symptoms at home were not serious. CONCLUSIONS: Monitoring of recurring symptoms
      following consumption of causative foods at home by patients with uncertain
      symptoms improves the diagnostic accuracy of an Open-OFC.

PMID- 29047184
TI  - Meeting the support needs of persons with mild intellectual disability or
      borderline intellectual functioning: still a long way to go.
AB  - BACKGROUND: Among persons with a mild intellectual disability or borderline
      intellectual functioning, differences in their characteristics imply that a
      differentiated approach is required to meet their needs. This retrospective study
      examined whether the history of support/treatment programs and the type of
      healthcare providers involved matched the specific support needs of persons with
      a mild intellectual disability or borderline intellectual functioning. METHOD:
      Five (previously identified) profiles of persons with a mild intellectual
      disability or borderline intellectual functioning were used to investigate to
      what extent the support needs of this group had been met. For the 250 persons
      with mild intellectual disability or borderline intellectual functioning who
      matched these five profiles, data were collected retrospectively from their case
      files. RESULTS: Persons with mild intellectual disability or borderline
      intellectual functioning received a very similar amount and type of
      support/treatment programs. Differences between the profiles were found for non
      verbal therapy, residential treatment and contacts with social work. Regarding
      the type of healthcare providers involved, differences between the profiles
      emerged for specialised intellectual disability services, youth services and
      specialised addiction services. CONCLUSIONS: The support programs for a
      heterogeneous population of persons with mild intellectual disability or
      borderline intellectual functioning seem to be suboptimal, indicating that more
      differentiation is required in the services offered to these individuals.

PMID- 29047185
TI  - Pluripotent Stem Cell-Derived Hematopoietic Progenitors Are Unable to
      Downregulate Key Epithelial-Mesenchymal Transition-Associated miRNAs.
AB  - Hematopoietic stem cells derived from pluripotent stem cells could be used as an
      alternative to bone marrow transplants. Deriving these has been a long-term goal
      for researchers. However, the success of these efforts has been limited with the
      cells produced able to engraft in the bone marrow of recipient animals only in
      very low numbers. There is evidence that defects in the migratory and homing
      capacity of the cells are due to mis-regulation of miRNA expression and are
      responsible for their failure to engraft. We compared the miRNA expression
      profile of hematopoietic progenitors derived from pluripotent stem cells to those
      derived from bone marrow and found that numerous miRNAs are too highly expressed
      in hematopoietic progenitors derived from pluripotent stem cells, and that most
      of these are inhibitors of epithelial-mesenchymal transition or metastasis
      (including miR-200b, miR-200c, miR-205, miR-148a, and miR-424). We hypothesize
      that the high expression of these factors, which promote an adherent phenotype,
      may be causing the defect in hematopoietic differentiation. However, inhibiting
      these miRNAs, individually or in multiplex, was insufficient to improve
      hematopoietic differentiation in vitro, suggesting that other miRNAs and/or genes
      may be involved in this process. Stem Cells 2018;36:55-64.

PMID- 29047186
TI  - IL-1RN gene polymorphisms are associated with breast cancer risk in a Chinese Han
      population.
AB  - BACKGROUND: The interleukins (ILs) are a large family of endogenous cytokines
      that are crucial in the regulation of inflammation and immunological responses.
      The IL-1 receptor antagonist (IL-1RN) has been found to be associated with risk
      breast cancer (BC) in Korean and Indian women. However, little information is
      found about the polymorphisms of IL-1RN in Chinese Han BC patients. METHODS: We
      investigated the association between single-nucleotide polymorphisms (SNPs) in IL
      1RN and BC risk in a case-control study that included 530 BC cases and 628
      healthy controls. Six tag SNPs in IL-1RN were selected and genotyped using the
      Sequenom MassARRAY platform (Sequenom, San Diego, CA, USA). Odds ratios (ORs) and
      95% confidence intervals (CIs) were calculated using unconditional logistic
      regression after adjusting for age and sex. RESULTS: In the allele model, we
      found that the frequency of the 'T' allele of rs928940 was significantly lower in
      BC cases than in controls (OR = 0.776, 95% CI = 0.611-0.985, p = 0.037). In the
      genetic model analysis, five susceptibility SNPs were found to be associated with
      BC risk: the minor allele 'G' of rs315919, rs3181052 and rs452204 were associated
      with a decreased risk of BC under dominant model (p < 0.05), whereas the minor
      alleles 'T' and 'C' of rs928940 and rs4252019 were associated with a decreased
      risk of BC under both the codominant and dominant models (p < 0.05), which
      suggested these SNPs may play a protective role against BC risk. The haplotype
      'TAGC' constructed by rs928940, rs3181052, rs452204 and rs4252019 was associated
      with a decreased risk of BC (OR = 0.33; 95% CI = 0.12-0.94; p = 0.038).
      CONCLUSIONS: The data obtained in the present study shed new light on the
      association between genetic polymorphisms of IL-1RN and BC susceptibility in the
      Chinese Han population.

PMID- 29047187
TI  - A novel HIF1AN substrate KANK3 plays a tumor-suppressive role in hepatocellular
      carcinoma.
AB  - The KN motif and ankyrin repeat domain-containing protein (KANK) family is
      involved in actin cytoskeleton organization and cell motility. Compared with
      other KANK members, the biological function of KANK3 is not clear. Here, we
      identified KANK3 as a new substrate for the oxygen sensor hypoxia-inducible
      factor 1-alpha inhibitor (HIF1AN), which hydroxylates HIF-1/2alpha and other
      ankyrin repeat domain-containing proteins at asparagine residues. An in vitro
      hydroxylation assay clearly demonstrated asparaginyl hydroxylation of KANK3 by
      HIF1AN, and mass spectroscopic analysis revealed that KANK3 is hydroxylated at
      three asparagine residues within the ankyrin repeat domain. Bioinformatics
      analysis revealed that KANK3 downregulation is correlated with a poor prognosis
      in several types of cancers, including hepatocellular carcinoma (HCC). In HCC
      cells, KANK3 knockdown enhanced cell migration and invasion, while its
      overexpression inhibited these cell behaviors. Interestingly, such effects of
      KANK3 were not observed under hypoxic conditions, suggesting oxygen-dependent
      activity of KANK3. Based on these data, we propose that KANK3 acts as a tumor
      suppressor to control cancer behavior in an oxygen-dependent manner.

PMID- 29047189
TI  - Cerebral blood flow in the central autonomic network: is there any effect of
      hemispheric lateralization in patients with heart failure? Reply.

PMID- 29047188
TI  - Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant
      chemotherapy in BRCA-negative breast cancers.
AB  - It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the
      relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant
      chemotherapy in sporadic breast cancer patients has not been well established.
      Here, we investigate the association between BRCA1 or BRCA2 mRNA expression
      levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer
      patients who received neoadjuvant chemotherapy. BRCA1 and BRCA2 mRNA expression
      were assessed using quantitative real-time polymerase chain reaction in core
      biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant
      chemotherapy. A total 129 patients (19.1%) achieved pathological complete
      response (pCR) after neoadjuvant chemotherapy. Among patients treated with
      anthracycline-based chemotherapy (n = 531), BRCA1 mRNA low expression patients
      had a significantly higher pCR rate than intermediate or high BRCA1 mRNA
      expression groups (24.6% vs 16.8% or 14.0%, P = .031) and retained borderline
      significance (OR = 1.54, 95% CI = 0.93-2.56, P = .094) in multivariate analysis.
      Among the 129 patients who received a taxane-based regimen, pCR rate showed no
      differences in BRCA1 low, intermediate, and high mRNA level subgroups (19.6%,
      26.8% and 21.4%, respectively; P = .71). BRCA2 mRNA level was not associated with
      pCR rate in the anthracyline-based treated subgroup (P = .60) or the taxane-based
      regimen subgroup (P = .82). Taken together, our findings suggested that BRCA1
      mRNA expression could be used as a predictive marker in BRCA1/2 mutation-negative
      breast cancer patients who received neoadjuvant anthracycline-based treatment.

PMID- 29047190
TI  - Relationship between gastric lanthanum deposition and Helicobacter pylori
      associated chronic gastritis: is it rare or common?

PMID- 29047191
TI  - Concise Review: Wnt Signaling Pathways in Skin Development and Epidermal Stem
      Cells.
AB  - Mammalian skin and its appendages constitute the integumentary system forming a
      barrier between the organism and its environment. During development, skin
      epidermal cells divide rapidly and stratify into a multilayered epithelium, as
      well as invaginate downward in the underlying mesenchyme to form hair follicles
      (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously
      proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal
      regeneration is fueled by epidermal stem cells (SCs) located in the basal layer
      of the IFE and the outer layer of the bulge in the HF. Epidermal development and
      SC behavior are mainly regulated by various extrinsic cues, among which Wnt
      dependent signaling pathways play crucial roles. This review not only summarizes
      the current knowledge of Wnt signaling pathways in the regulation of skin
      development and governance of SCs during tissue homeostasis, but also discusses
      the potential crosstalk of Wnt signaling with other pathways involved in these
      processes. Stem Cells 2018;36:22-35.

PMID- 29047192
TI  - Palladium-Catalyzed Cross-Coupling of Nitroarenes.
AB  - Pd at the crossroads: The palladium-catalyzed cross-coupling of nitroarenes has
      eluded chemists for decades. Recently, the first palladium-catalyzed Suzuki
      Miyaura and Buchwald-Hartwig cross-couplings of nitroarenes were reported.
      Mechanistically, this process involves the challenging oxidative addition of LPd0
      into the Ar-NO2 bond. This process features a broad substrate scope with respect
      to both the nitroarene and the nucleophilic coupling partners.

PMID- 29047193
TI  - Unlicensed pharmaceutical preparations for clinical patient care: Ensuring
      safety.
AB  - Most medicinal products dispensed to patients have marketing authorization (MA)
      to ensure high quality of the product, safety, and efficacy. However, in daily
      practice, to treat patients adequately, there is a medical need for drugs that do
      not hold MA. To meet this medical need, medicinal products are used in clinical
      care without MA (unlicensed), such as products prepared by (local) pharmacies:
      the pharmaceutical preparations. Three types of pharmaceutical preparations are
      distinguished: (i) reconstitution in excess of summary of product
      characteristics; (ii) adaptation of a licensed medicinal product (outside its
      official labeling); (iii) medicinal products from an active pharmaceutical
      ingredient. Although unlicensed, patients may expect the same quality for these
      unlicensed pharmaceutical preparations as for the licensed medicinal products. To
      assure this quality, a proper risk-benefit assessment and proper documentation in
      (centralized) patient registries and linking to a national pharmacovigilance
      database should be in place. Based on a risk assessment matrix, requirements for
      quality assurance can be determined, which has impact on the level of
      documentation of a pharmaceutical preparation. In this paper, the approach for
      good documentation including quality assurance and benefit-risk assessment will
      be discussed and possibilities for patient registries are described to make these
      crucial preparations available for regular patient care. KEY POINTS Ensuring
      pharmaceutical quality and performing a proper benefit-risk assessment will
      guarantee safe use of pharmaceutical preparations. Good documentation of (ultra
      )orphan treatments can be collected in centralized patient registries and should
      be combined with existing information in (inter)national databases and self
      reflection of patients. Linking patient registries to a centralized database for
      adverse drug events is highly recommended as it increases safety control of the
      (ultra) orphan pharmaceutical preparations.

PMID- 29047194
TI  - Gerard Ferey (1941-2017).
AB  - Gerard Ferey, a leader in the field of solid-state chemistry and a pioneer of
      metal-organic frameworks (MOFs), passed away on August 19, 2017 in Paris. Ferey
      developed both open-framework templated metal fluorophosphates (the ULM-n series)
      and a series of topical porous MOFs (the MIL-n series). He also created the
      automated assembly of secondary building units methodology to predict the
      structure of new porous solids.

PMID- 29047195
TI  - Hepatic transudation barrier properties.
AB  - OBJECTIVE: Fluid and protein continuously transude from the surface of the liver.
      Despite a common understanding that transudation plays a critical role in hepatic
      interstitial and peritoneal fluid balance, transudation from the entire liver has
      not been studied. Therefore, the goal of the present work was to provide the
      first direct measurement of the hepatic transudation rate and transudation
      barrier properties. METHODS: Transudation rates were determined by collecting
      transudate from the entire liver. Hydraulic conductivity, and fluid transudation
      and protein reflection coefficients of the transudation barrier (formed by the
      subscapular interstitial matrix, capsule, and peritoneum) were determined from
      changes in fluid and protein transudation rates in response to hepatic venous
      pressure elevation. RESULTS: Following hepatic venous pressure elevation from 6.1
      +/- 0.9 to 11.1 +/- 0.6 mm Hg, transudation rate increased from 0.13 +/- 0.03 to
      0.37 +/- 0.03 mL/min.100 g. Transudation barrier hydraulic conductivity, fluid
      transudation and protein reflection coefficients (3.9 * 10-4  +/- 5.7 * 10-5 
      mL/min.mm Hg.cm2 , 0.36 +/- 0.04 mL/min.mm Hg, and 0.09 +/- 0.03, respectively)
      were comparable to those reported for hepatic sinusoids. CONCLUSIONS: Taken
      together, these findings suggest that the hepatic transudation barrier is highly
      permeable at elevated sinusoidal pressures. These fundamental studies provide a
      better understanding of the hepatic transudation barrier properties and
      transudation under conditions that are physiologically and clinically relevant to
      ascites formation.

PMID- 29047196
TI  - To what extent do data from pharmaceutical claims under-estimate opioid analgesic
      utilisation in Australia?
AB  - PURPOSE: Although pharmaceutical claims are an essential data source for
      pharmacoepidemiological studies, these data potentially under-estimate opioid
      utilisation. Therefore, this study aimed to quantify the extent to which
      pharmaceutical claims from Australia's national medicines subsidy programs
      (Pharmaceutical Benefits Scheme [PBS] and Repatriation Schedule of Pharmaceutical
      Benefits [RPBS]) under-estimate prescription-only and total national opioid
      utilisation across time and for different opioids. A secondary aim was to examine
      the impact of the 2012 policy change to record all PBS/RPBS dispensed medicines,
      irrespective of government subsidy, on the degree of under-estimation. METHODS:
      Aggregated data on Australian opioid utilisation were obtained for the 2010 to
      2014 calendar years, including all single ingredient and combination opioid
      analgesic preparations available on prescription or over-the-counter (OTC). Total
      opioid utilisation (oral morphine equivalent kilogrammes) was quantified using
      sales data from IMS Health and compared with pharmaceutical claims data from the
      PBS/RPBS. RESULTS: PBS/RPBS claims data did not account for 12.4% of prescription
      only opioid utilisation in 2014 and 19.1% in 2010, and 18.4% to 25.4% of total
      opioid use when accounting for OTC preparations. Between 2010 and 2014, 5.6% to
      5.3% of buprenorphine, 8.1% to 6.3% fentanyl, 17.7% to 10.7% oxycodone, 18.4% to
      11.0% tramadol, 38.4% to 21.0% hydromorphone, and 28.6% to 21.0% of prescription
      only codeine utilisation were not accounted for in PBS/RPBS claims. CONCLUSIONS:
      Despite increased capture of less expensive (under co-payment) opioid items since
      2012, PBS/RPBS claims still under-estimate opioid use in Australia, with varying
      degrees across opioids. The estimates generated in this study allow us to better
      understand the degree of under-estimation and account for these in research using
      Australia's national pharmaceutical claims data.

PMID- 29047197
TI  - Locus of control, optimism, and recollections of depression and self-reported
      cognitive functioning following treatment for colorectal cancer.
AB  - OBJECTIVE: To investigate the effects of disposition (locus of control, optimism,
      and depression) on recollections of cognitive functioning following cancer
      treatment. METHODS: Participants were survivors of colorectal cancer (n = 88) and
      their spouses (n = 40). Survivors retrospectively rated their cognitive
      functioning and depression, as experienced following treatment and currently
      rated their dispositions for optimism and locus of control. Survivors' spouses
      likewise provided their recollections of survivors' cognitive functioning and
      depression at time following treatment. RESULTS: Correlations between survivors'
      and spouses' ratings for cognitive functioning were statistically significant but
      not for depression. Results supported validity of survivors' longer term
      retrospective reports. Although internal locus of control correlated positively
      with retrospectively self-reported cognitive functioning, and negatively with
      retrospectively self-reported depression, moderated hierarchical multiple
      regression found independent contribution of internal locus of control was
      limited to predicting quality of life; and that, among variables tested,
      depression correlated strongest with cognitive functioning. CONCLUSIONS: Neither
      internal locus of control nor optimism in colorectal cancer survivors influences
      correlation between cognition and depression. Health care providers should note
      individual differences in responses to treatment and be alert to the impact of
      depression on perceived everyday functioning.

PMID- 29047198
TI  - Evaluation of narrow band ultraviolet B phototherapy in the treatment of chronic
      actinic dermatitis in Chinese patients.
AB  - Few studies have been conducted in chronic actinic dermatitis (CAD) treated with
      narrowband ultraviolet B (NB UVB) phototherapy, especially in Asian patients. We
      aim to evaluate the efficacy and safety of NB UVB phototherapy in Chinese
      patients with CAD. 19 CAD patients of Fitzpatrick skin phototype IV received NB
      UVB phototherapy in spring and treatments were given 3 times weekly with
      incremental dose and maintenance therapy was given twice weekly for 3-4 weeks.
      The mean initial, endpoint, and cumulative dose of NB UVB was 0.08, 0.33, and 6.0
      J/cm2 , respectively. Patients totally received 27 times of treatments in
      average. 87.5% of previously ultraviolet B(UVB) sensitive patients and 75% of
      previously ultraviolet A(UVA) sensitive patients had normal or improved MED after
      phototherapy. The percentage of patients returned to normal UVB phototesting was
      higher than that of patients returned to normal UVA phototesting (68.8% vs.
      37.5%). The mean 1-week DLQI and the need for using immunosuppressive agents and
      antihistamines were significantly reduced after treatment (p < .01 or p < .05).
      In conclusion, prophylactic NB UVB phototherapy is effective and safe in
      treatment of CAD in Chinese patients with Fitzpatrick skin phototype IV.

PMID- 29047199
TI  - Student veterans' construction and enactment of resilience: A constructivist
      grounded theory study.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Resilience is an ability and a process that
      allows an individual to develop positive adaptation despite challenges and
      adversities. Many military veterans returning to college after their military
      service have difficulty transitioning to civilian life. Although some research
      exists that explores factors related to the resilience of college student
      veterans, limited theoretical descriptions exist that explain how student
      veterans construct resilience, and how resilience is enacted and enhanced in
      their academic and personal (non-academic) lives. WHAT THIS PAPER ADDS TO
      EXISTING KNOWLEDGE?: The resilience of student veterans involves a complex
      process of transitioning from military to civilian life and an iterative journey
      between positive adaptation and transient perturbations. Student veterans'
      resilience is a result of integrating and resolving various aspects of their
      academic and personal challenges. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses
      can apply this grounded theory as a practical framework for equipping student
      veterans with effective strategies to develop and enhance resilience. Nurses can
      employ a holistic approach of care in their interactions with military veterans
      and student veterans that includes fostering psychological resilience, helping to
      manage their multiple non-academic responsibilities and supporting their academic
      success. ABSTRACT: Introduction Adjusting to college life is one of the most
      difficult experiences in a military veteran's transition to civilian life. Many
      military veterans returning to college not only encounter academic challenges,
      but also deal with physical and psychiatric disabilities, loss of military
      camaraderie and social disconnect. These often negatively affect their personal
      and academic lives. Hence, it is important to explore resilience to best support
      student veterans as they transition from military to civilian life. Aim The aim
      of this study was to explore how student veterans construct and enact resilience
      within their personal and academic lives. Method Using constructivist grounded
      theory methodology, in-depth individual interviews were conducted with 20
      military veterans enrolled as undergraduate students at a U.S. university.
      Results The process of "integrating," which represents student veterans'
      construction and enactment of resilience, was the core category. This category
      has three subcategories: (1) the aspects; (2) the expressions; and (3) the
      enactments of resilience. Implications for practice Nurses can use this grounded
      theory as the practical framework for their interactions with military veterans,
      and more particularly with supporting student veterans in their academic lives,
      in their personal lives and in the transition from military to civilian life.

PMID- 29047200
TI  - Interactions between fawns and does of farmed fallow deer Dama dama in the
      postnatal period.
AB  - The aim of the present study was to describe the suckling behavior of the
      offspring of farmed European fallow deer Dama dama in the postnatal period. Video
      surveillance footage from the first 18 days postpartum was analyzed in detail to
      reveal that the duration of interactions between the mother and the offspring
      changed with the fawns' age. The duration of mother-offspring interactions was
      longest between postpartum days 12 and 18. The frequency of interactions at
      different times of the day varied in the analyzed periods. The results of the
      study could be used to increase the welfare of farmed deer.

PMID- 29047201
TI  - Using copulas to estimate the coefficient of a binary endogenous regressor in a
      Poisson regression: Application to the effect of insurance on doctor visits.
AB  - This paper presents a copula-based method for identifying and estimating the
      coefficient of a binary endogenous regressor in a Poisson regression. The method
      offers advantages over existing approaches. Most importantly, it relies upon
      standard maximum likelihood approaches, and it does not require numerical
      integration. Further, as part of its implementation, the method provides a
      convenient test for the presence of endogeneity. The empirical application
      investigates the effect of insurance status (a binary measure) on doctor visits
      (a count measure).

PMID- 29047202
TI  - Unsymmetrical Biaryl Compounds: Metal- and Reagent-Free Electrochemical Couplings
      Are on the Advance.
AB  - It's electrifying! Electrochemical cross-coupling of aryl compounds provides a
      one-step approach to unsymmetrical biaryl compounds. A boron-doped diamond
      electrode is used as the anode to oxidise the phenolic hydroxy group to a phenoxy
      radical, with 1,1,1,3,3,3-hexafluoroisopropylalcohol (HFIP) and
      tetraalkylammonium methylsulfate used as the solvent and electrolyte. Since no
      reagents are required, no waste is formed from this source.

PMID- 29047203
TI  - Engineered cross-reacting nanobodies simplify comparative oncology between humans
      and dogs.
AB  - Antibodies cross-reacting with homologue antigens in different species would be
      essential reagents for the development of comparative oncology studies. In
      comparison with conventional immunoglobulin Gs, recombinant nanobodies (single
      domain variable regions of heavy-chain only antibodies of Camelidae origin) can
      be easily isolated in vitro and engineered into a variety of reagents with
      optimized characteristics for different research and clinical applications. We
      recovered an anti-human epidermal growth factor receptor 2 (anti-HER2) nanobody
      from a naive llama library by direct panning on whole cells and expressed it
      fused to Fc and green fluorescent protein. These immunoreagents were assessed by
      flow cytometry and immunofluorescence with both human and canine cells
      overexpressing HER2 and its canine homologue dog epidermal growth factor receptor
      2. The reported data illustrate the potential of using this class of antibodies
      in comparative oncology and suggest some development perspectives enabled by in
      vitro panning of pre-immune nanobody libraries.

PMID- 29047204
TI  - Influence of cell distribution and diabetes status on the association between
      mitochondrial DNA copy number and aging phenotypes in the InCHIANTI study.
AB  - Mitochondrial DNA copy number (mtDNA-CN) estimated in whole blood is a novel
      marker of mitochondrial mass and function that can be used in large population
      based studies. Analyses that attempt to relate mtDNA-CN to specific aging
      phenotypes may be confounded by differences in the distribution of blood cell
      types across samples. Also, low or high mtDNA-CN may have a different meaning
      given the presence of diseases associated with mitochondrial damage. We evaluated
      the impact of blood cell type distribution and diabetes status on the association
      between mtDNA-CN and aging phenotypes, namely chronologic age, interleukin-6,
      hemoglobin, and all-cause mortality, among 672 participants of the InCHIANTI
      study. After accounting for white blood cell count, platelet count, and white
      blood cell proportions in multivariate models, associations of mtDNA-CN with age
      and interleukin-6 were no longer statistically significant. Evaluation of a
      statistical interaction by diabetes status suggested heterogeneity of effects in
      the analysis of mortality (P < 0.01). The magnitude and direction of associations
      between mtDNA-CN estimated from blood samples and aging phenotypes are influenced
      by the sample cell type distribution and disease status. Therefore, accounting
      for these factors may aid understanding of the relevance of mitochondrial DNA
      copy number to health and aging.

PMID- 29047205
TI  - Experimental precipitation of apatite pseudofossils resembling fossil embryos.
AB  - Certain phosphatic grains preserved in the rock record are interpreted as
      microfossils representing a diversity of microorganisms from bacteria to fossil
      embryos. In addition to bona fide primary biological features, phosphatic
      microfossils and fossil embryos commonly exhibit features that result from
      abiotic precipitation or diagenetic alteration. Distinguishing between abiotic
      and primary biological features can be difficult, and some features thought to
      represent biological tissue could instead be artifacts that are unrelated to the
      original morphology of a preserved organism. Here, we present experimentally
      generated, abiotically produced mineral precipitates that morphologically
      resemble biologically produced features, some of which may be observed in the
      rock record or noted in extant organisms, including embryos. These findings
      extend the diversity of biomorphic features known to result from abiotic
      precipitation.

PMID- 29047206
TI  - Determining the cross-talk between smooth muscle cells and macrophages on a
      cobalt-chromium stent material surface using an in vitro postimplantation
      coculture model.
AB  - Smooth muscle cells (SMCs) and macrophages are important cellular components
      involved in the development of complications following the implantation of
      cardiovascular devices. This leads to various disorders such as restenosis,
      chronic inflammation, and may ultimately result in device failure. In this study,
      we developed a postimplant stent coculture model using different ratios of SMCs
      and macrophages seeded on to cobalt-chromium alloy. The macrophages had an
      increased affinity to the coculture surfaces, which resulted in decreased SMC
      attachment to the alloy surfaces at the initial time point. Once adhered, the
      macrophages spread freely and displayed advanced stages of inflammation at 48 h
      when cocultured with SMCs. This resulted in an increased secretion of
      proinflammatory cytokines (tumor necrosis factor alpha, monocyte chemotactic
      protein 1, interleukin [IL]-6, and IL-8) by 48 h in the coculture samples with
      the greatest increase observed with the high number of macrophages. Therefore,
      the increased levels of proinflammatory cytokines promoted the growth of SMCs in
      coculture to a greater extent than when the SMCs were culture alone. Thus, this
      study demonstrated the constant cross-talk between SMCs and macrophages occurring
      on the postimplant stent surface. Similar coculture models can be used to test
      the biocompatibility of drugs and biomaterials at possible postimplantation
      scenarios. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 673
      685, 2018.

PMID- 29047207
TI  - Effects of probiotics on body weight, body mass index, fat mass and fat
      percentage in subjects with overweight or obesity: a systematic review and meta
      analysis of randomized controlled trials.
AB  - A systematic review and meta-analysis of randomized controlled trials was
      conducted to examine the effects of probiotic supplementation on body weight,
      body mass index (BMI), fat mass and fat percentage in subjects with overweight
      (BMI 25-29.9 kg m-2 ) or obesity (BMI >=30 kg m-2 ). MEDLINE, EMBASE and the
      Cochrane Central Register of Controlled Trials were searched for studies
      published between 1946 and September 2016. A meta-analysis, using a random
      effects model, was performed to calculate the weighted mean difference between
      the intervention and control groups. Of 800 studies identified through the
      literature search, 15 were finally included. The studies comprised a total of 957
      subjects (63% women), with the mean BMI being 27.6 kg m-2 and the duration of the
      interventions ranging from 3 to 12 weeks. Administration of probiotics resulted
      in a significantly larger reduction in body weight (weighted mean difference [95%
      confidence interval]; -0.60 [-1.19, -0.01] kg, I2  = 49%), BMI (-0.27 [-0.45, 
      0.08] kg m-2 , I2  = 57%) and fat percentage (-0.60 [-1.20, -0.01] %, I2  = 19%),
      compared with placebo; however, the effect sizes were small. The effect of
      probiotics on fat mass was non-significant (-0.42 [-1.08, 0.23] kg, I2  = 84%).

PMID- 29047208
TI  - Expression of aromatase in the rostral ventromedial medulla and its role in the
      regulation of visceral pain.
AB  - AIMS: Estrogens are known to exert a wide spectrum of actions on brain functions
      including modulation of pain. Besides the circulating estrogens produced mainly
      by the ovaries, many brain regions are also capable of de novo synthesizing
      estrogens, which may exert important modulatory effects on neuronal functions.
      This study was aimed to test the hypothesis that aromatase, the enzyme that
      catalyzes the conversion of testosterone to estradiols, may be distributed in the
      rostral ventromedial medulla (RVM), where it may impact on visceral pain. METHODS
      AND RESULTS: Adult female rats were treated with cyclophosphamide (CPM, 50 mg/kg,
      ip, once every 3 days) or saline. At approximately day 10 following the 3rd
      injection, CPM-treated rats exhibited colorectal hyperalgesia as they showed
      significantly greater abdominal withdrawal responses (AWR) to graded colorectal
      distension (CRD, 0-100 mm Hg) than the saline group. Immunofluorescent staining
      and Western blot assay revealed that CPM-induced colorectal hyperalgesia was
      associated with significantly increased expression of aromatase and
      phosphorylated MU-type opioid receptor (pMOR) and decreased expression of total
      MOR in the RVM. Intracisternal application of aromatase inhibitors, fadrozole,
      and letrozole reversed CPM-induced colorectal hyperalgesia and restored pMOR and
      MOR expression in the RVM. CONCLUSIONS: Our observations confirmed the expression
      of aromatase in the RVM, a pivotal brain region in descending modulation of pain
      and opioid analgesia. The results support the hypothesis that locally produced
      estrogens in the RVM may be involved in the maintenance of chronic visceral
      hyperalgesia and the downstream signaling may involve phosphorylation of MOR.

PMID- 29047209
TI  - Effects of cryopreservation on adipose tissue-derived microvascular fragments.
AB  - Adipose tissue-derived microvascular fragments (ad-MVF) are effective
      vascularization units for tissue engineering. They rapidly reassemble into new
      microvascular networks after seeding on scaffolds and subsequent in vivo
      implantation. Herein, we analyzed whether the vascularization capacity of ad-MVF
      is affected by cryopreservation. Ad-MVF were isolated from the epididymal fat
      pads of C57BL/6 mice and cryopreserved for 7 days to compare their morphology,
      viability, cellular composition, and protein expression with freshly isolated
      control ad-MVF. Moreover, cryopreserved and control ad-MVF from green fluorescent
      protein (GFP)+ donor mice were seeded on collagen-glycosaminoglycan matrices
      (Integra(r) ), which were implanted into dorsal skinfold chambers of GFP-
      recipient animals to study their vascularization and incorporation using
      intravital fluorescence microscopy, histology, and immunohistochemistry.
      Cryopreservation of ad-MVF did not affect vessel morphology and cellular
      composition. However, cryopreservation was associated with an increased rate of
      necrotic cells and a significantly reduced number of transplantable ad-MVF. This
      was compensated by a higher angiogenic activity of the remaining ad-MVF, as
      indicated by significantly elevated expression levels of pro-angiogenic factors
      when compared to controls. Accordingly, cryopreserved and control ad-MVF induced
      a comparable vascularization and incorporation of implanted Integra(r) without
      differences in microvascular network formation, maturation, and remodeling.
      Enhanced angiogenic sprouting even resulted in a higher fraction of GFP+
      microvessels within the implants of the cryopreservation group. These findings
      indicate that cryopreservation of ad-MVF is feasible and, thus, offers the
      exciting opportunity to build up stocks of readily available vascularization
      units for future tissue engineering applications.

PMID- 29047210
TI  - Environmental insights from high-resolution (SIMS) sulfur isotope analyses of
      sulfides in Proterozoic microbialites with diverse mat textures.
AB  - In modern microbial mats, hydrogen sulfide shows pronounced sulfur isotope
      (delta34 S) variability over small spatial scales (~500/00 over <4 mm), providing
      information about microbial sulfur cycling within different ecological niches in
      the mat. In the geological record, the location of pyrite formation, overprinting
      from mat accretion, and post-depositional alteration also affect both fine-scale
      delta34 S patterns and bulk delta34 Spyrite values. We report MUm-scale delta34 S
      patterns in Proterozoic samples with well-preserved microbial mat textures. We
      show a well-defined relationship between delta34 S values and sulfide mineral
      grain size and type. Small pyrite grains (<25 MUm) span a large range, tending
      toward high delta34 S values (-54.50/00 to 11.70/00, mean: -14.40/00). Larger
      pyrite grains (>25 MUm) have low but equally variable delta34 S values (-61.00/00
      to -10.50/00, mean: -44.40/00). In one sample, larger sphalerite grains (>35 MUm)
      have intermediate and essentially invariant delta34 S values (-22.60/00 to 
      15.60/00, mean: -19.40/00). We suggest that different sulfide mineral populations
      reflect separate stages of formation. In the first stage, small pyrite grains
      form near the mat surface along a redox boundary where high rates of sulfate
      reduction, partial closed-system sulfate consumption in microenvironments, and/or
      sulfide oxidation lead to high delta34 S values. In another stage, large
      sphalerite grains with low delta34 S values grow along the edges of pore spaces
      formed from desiccation of the mat. Large pyrite grains form deeper in the mat at
      slower sulfate reduction rates, leading to low delta34 Ssulfide values. We do not
      see evidence for significant 34 S-enrichment in bulk pore water sulfide at depth
      in the mat due to closed-system Rayleigh fractionation effects. On a local scale,
      Rayleigh fractionation influences the range of delta34 S values measured for
      individual pyrite grains. Fine-scale analyses of delta34 Spyrite patterns can
      thus be used to extract environmental information from ancient microbial mats and
      aid in the interpretation of bulk delta34 Spyrite records.

PMID- 29047211
TI  - Exploring the nature of illness perceptions in people with end-stage kidney
      disease.
AB  - BACKGROUND: Diagnosis and treatment for End-Stage Kidney Disease (ESKD) results
      in vast lifestyle changes. Despite the high prevalence of depression in people
      with ESKD, the psychosocial impacts of ESKD are still often overlooked. Illness
      perceptions enable people to make sense of their illness and are closely
      associated with depression. Due to the high levels of depression within ESKD,
      this study sought to understand the nature of illness perceptions in people with
      ESKD. METHODOLOGY: In this qualitative study, eleven participants were identified
      through hospital and online patient support groups. Semi-structured interviews
      were audio-taped, transcribed and analysed using grounded theory techniques.
      RESULTS: Three themes emerged from the data: Renal Conflicts, Forced Adjustment
      and Coping. The main dimensions of illness perception discussed by participants
      were Consequences, Control, Timeline and Identity. CONCLUSION: The results of
      this study have practical implications for informing practitioners about the
      psychosocial effects of ESKD diagnosis and treatment.

PMID- 29047212
TI  - A Nickel-Catalyzed Carbonyl-Heck Reaction.
AB  - The use of transition-metal catalysis to enable the coupling of readily available
      organic molecules has greatly enhanced the ability of chemists to access complex
      chemical structures. In this work, an intermolecular coupling reaction that
      unites organotriflates and aldehydes is presented. A unique catalyst system is
      identified to enable this reaction, featuring a Ni0 precatalyst, a tridentate
      Triphos ligand, and a bulky amine base. This transformation provides access to a
      variety of ketone-containing products without the selectivity- and reactivity
      related challenges associated with more traditional Friedel-Crafts reactions. A
      Heck-type mechanism is postulated, wherein the pi bond of the aldehyde takes the
      role of the olefin in the insertion/elimination steps.

PMID- 29047213
TI  - Baseline and Time-Averaged Values Predicting Residual Renal Function Decline Rate
      in Japanese Peritoneal Dialysis Patients.
AB  - Residual renal function (RRF) is a strong prognostic factor of morbidity and
      mortality in patients undergoing peritoneal dialysis (PD). We determined
      predictors of the RRF rate of decline using both baseline values and time
      averaged ones. We retrospectively analyzed 94 patients being treated with PD at
      the Japanese Red Cross Medical Center. The decline rate of RRF was calculated by
      a diminution in the weekly renal Kt/V between the first and last follow up
      divided by follow-up years. The mean follow-up period was 2.28 years, and the
      mean decline rate of weekly renal Kt/V was 0.25 per year. A multivariate analysis
      using baseline parameters identified dialysis-to-plasma ratios of creatinine at 4
      h (P = 0.02), urinary protein (P = 0.02), and mean blood pressure (MBP) (P <
      0.01) as being positively associated with the RRF rate of decline, while the use
      of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker
      (ARB) had a negative correlation (P = 0.03). When using time-averaged values as
      independent variables, a lower weekly total renal Kt/V (P < 0.0001), higher
      urinary protein (P < 0.0001), and higher MBP (P = 0.04) independently predicted a
      faster RRF rate of decline. We demonstrated that PD patients with a lower MBP and
      lower urinary protein both at baseline and throughout their PD duration had a
      slower RRF rate of decline. We recommend strict control of blood pressure and
      anti-proteinuric therapy for PD patients.

PMID- 29047214
TI  - Tanshinone IIA alleviates lipopolysaccharide-induced acute lung injury by
      downregulating TRPM7 and pro-inflammatory factors.
AB  - The study aimed to investigate the role of Tanshinone IIA (Tan IIA) in
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) in its regulation of
      TRPM7. Wistar male rats were randomly divided into the normal saline (NS), LPS,
      knockout (KO) + LPS, low-dose Tan IIA (Tan-L), middle-dose Tan IIA (Tan-M), high
      dose Tan IIA (Tan-H) and KO + high-dose Tan IIA (KO + Tan-H) groups. The level of
      tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, TRPM7
      protein expression, current density-voltage curve and Ca2+ concentration were
      detected through ELISA, Western blotting, electrophysiological experiment and a
      calcium-imaging technique, respectively. The rats in the KO + LPS, Tan-L, Tan-M,
      Tan-H and KO + Tan-H groups all displayed lower levels of TNF-alpha, IL-1beta and
      IL-6 than the LPS group. Rats in the KO + Tan-H group exhibited lower levels of
      NF-alpha, IL-1beta and IL-6 than rats in the Tan-H group. Elevated levels of
      TRPM7 protein expression in the LPS and Tan groups were detected in comparison
      with the NS group. However, TRPM7 protein expression in Tan-M and Tan-H groups
      was notably lower than in that of the LPS group. In comparison with the NS group,
      the LPS and Tan groups had a greater PIMs cell density and a higher concentration
      of Ca2+ . Contrary results were observed in the KO + LPS, Tan-H and KO + Tan-H
      groups. Tan IIA decreases calcium influx in PIMs and inhibits pro-inflammatory
      factors which provide an alleviatory effect in regards to LPS-induced ALI by
      suppressing TRPM7 expression.

PMID- 29047215
TI  - Acute cardiovascular effects of bitter orange extract (p-synephrine) consumed
      alone and in combination with caffeine in human subjects: A placebo-controlled,
      double-blind study.
AB  - The purpose was to examine cardiovascular responses to supplementation with p
      synephrine alone and in combination with caffeine during quiet sitting. Sixteen
      subjects were given (in double-blind manner) either 103 mg of p-synephrine (S),
      233 mg of caffeine +104 mg of p-synephrine (LC + S), 240 mg of caffeine (LC), 337
      mg of caffeine +46 mg of p-synephrine (HC + S), 325 mg of caffeine (HC), or a
      placebo. The subjects sat quietly for 3 hr while heart rate (HR) and blood
      pressure were measured. Only HC + S and HC significantly increased mean systolic
      blood pressure (SBP) during the second hour and tended to increase mean SBP
      during the third hour. Mean diastolic blood pressure in S was significantly lower
      than the other trials during the first and second hours, and mean arterial
      pressure was significantly lower in S compared to the LC, LC + S, HC, and HC + S
      trials. No differences were observed in HR. Consumption of p-synephrine may
      acutely reduce diastolic blood pressure and mean arterial pressure and not affect
      SBP or HR during quiet sitting. The addition of p-synephrine to caffeine did not
      augment SBP or HR indicating that consumption of up to 104 mg of p-synephrine
      does not induce cardiovascular stress during quiet sitting.

PMID- 29047216
TI  - Uteroplacental insufficiency in rats induces renal apoptosis and delays
      nephrogenesis completion.
AB  - AIM: Uteroplacental insufficiency in rats reduces nephron endowment, leptin
      concentrations and programmes cardiorenal disease in offspring. Cross-fostering
      growth-restricted (Restricted) offspring onto a mother with normal lactation
      restores leptin concentrations and nephron endowment. This study aimed to
      determine whether the reduced nephron endowment in Restricted offspring is due to
      delayed glomerular formation and dysregulation of renal genes regulating
      branching morphogenesis, apoptosis or leptin signalling. Furthermore, we aimed to
      investigate whether cross-fostering Restricted offspring onto Control mothers
      could improve glomerular maturation and restore renal gene abundance. METHODS:
      Uteroplacental insufficiency was induced by bilateral uterine vessel ligation
      (Restricted) or sham (Control) surgery on gestation day 18 (E18). Kidneys were
      collected at E20, postnatal day 1 (PN1) and PN7. An additional cohort was cross
      fostered onto separate mothers at birth and kidneys collected at PN7. RESULTS:
      Kidneys were lighter in the Restricted group, but weight was restored with cross
      fostering. At E20, abundance of Bax, Flt1 and Vegfa was increased in Restricted
      offspring, while Ret and Bcl2 transcripts were increased only in Restricted
      females. At PN7, abundance of Gdnf and Ret was higher in Restricted offspring, as
      was Casp3. Restricted offspring had a wider nephrogenic zone with more immature
      glomeruli suggesting a delayed or extended nephrogenic period. Cross-fostering
      had subtle effects on gene abundance and glomerular maturity. CONCLUSION:
      Uteroplacental insufficiency induced apoptosis in the developing kidney and
      delayed and extended nephrogenesis. Cross-fostering Restricted offspring onto
      Control mothers had beneficial effects on kidney growth and renal maturity, which
      may contribute to the restoration of nephron endowment.

PMID- 29047218
TI  - Risk of Incident Chronic Obstructive Pulmonary Disease in Rheumatoid Arthritis: A
      Population-Based Cohort Study.
AB  - OBJECTIVE: Studies have demonstrated a link between chronic obstructive pulmonary
      disease (COPD) and inflammation, raising the question whether chronic
      inflammatory conditions, such as rheumatoid arthritis (RA), predispose to COPD.
      Our objective was to evaluate the risk of incident COPD hospitalization in RA
      compared to the general population. METHODS: We studied a population-based
      incident RA cohort with matched general population controls, using administrative
      health data. All incident RA cases in British Columbia who first met RA
      definition between January 1996 and December 2006 were selected using previously
      published criteria. General population controls were randomly selected, matched
      1:1 to RA cases on birth year, sex, and index year. COPD outcome was defined as
      hospitalization with a primary COPD code. Incidence rates, 95% confidence
      intervals (95% CIs), and incidence rate ratios (IRRs) were calculated for RA and
      controls. Multivariable Cox proportional hazards models estimated the risk of
      COPD in RA compared to the general population after adjusting for potential
      confounders. Sensitivity analyses were performed to test the robustness of the
      results to the possible confounding effect of smoking, unavailable in
      administrative data, and to COPD outcome definitions. RESULTS: The cohorts
      included 24,625 RA individuals and 25,396 controls. The incidence of COPD
      hospitalization was greater in RA than controls (IRR 1.58, 95% CI 1.34-1.87).
      After adjusting for potential confounders, RA cases had a 47% greater risk of
      COPD hospitalization than controls. The increased risk remained significant after
      modeling for smoking and with varying COPD definitions. CONCLUSION: In our
      population-based cohort, individuals with RA had a 47% greater risk of COPD
      hospitalization compared to the general population.

PMID- 29047217
TI  - Spotted fever group rickettsiae associated with ixodid ticks in wild environment
      in Southern Italy.
AB  - Ixodidae ticks are vectors and reservoirs of several species of rickettsiae, and
      tick-borne rickettsioses are reported worldwide. This study was aimed to verify
      the distribution of spotted fever group rickettsiae associated with ticks in a
      wild environment, the National Park of Gargano, where there is proximity between
      wild and domestic animals, and which is within an endemic area for rickettsiosis.
      Ticks were collected from animals or vegetation, morphologically identified and
      tested by a PCR targeting the 17kDa gene, and by a loop-mediated isothermal
      amplification (LAMP) targeting ompB gene. Out of 34 tested tick pools, 2 from
      Dermacentor marginatus, 1 from Ixodes ricinus, and 1 from Rhipicephalus turanicus
      resulted positive. Nucleotide sequences of amplicons showed high similarity with
      sequences from Rickettsia slovaca, Rickettsia raoultii, Rickettsia helvetica, and
      Rickettsia felis. The overall calculated infection rate was 26.19 per 1,000,
      while it rose up to 107.77 when only D. marginatus was considered. The results
      highlight the association among Ri. slovaca, Ri. raoultii, D. marginatus and wild
      boars from which infected ticks were collected. Finally, the study shows the low
      efficacy of the previously described LAMP method for the detection of Rickettsia
      spp., when compared to PCR, making urgent the development of most effective LAMP
      protocols.

PMID- 29047219
TI  - Addition of dipeptidyl peptidase-4 inhibitors to insulin treatment in type 2
      diabetes patients: A meta-analysis.
AB  - AIMS/INTRODUCTION: To evaluate the efficacy and safety of combining insulin
      therapy with dipeptidyl peptidase-4 (DPP-4) inhibitors compared with combining
      insulin therapy with a placebo or other antihyperglycemic agents. MATERIALS AND
      METHODS: A literature search was carried out via electronic databases. The
      inclusion criteria were randomized controlled trials comparing the addition of
      DPP-4 inhibitors to insulin with the addition of a placebo or other active
      hypoglycemic agents to insulin therapy, study duration of no less than 12 weeks
      carried out in type 2 diabetes patients and the availability of outcome data to
      evaluate a change in the glycated hemoglobin. RESULTS: The glycated hemoglobin
      lowering efficacy was significantly greater with DPP-4 inhibitor/insulin (DPP
      4i/INS) than with placebo/insulin (weighted mean difference -0.53%, 95%
      confidence interval -0.63, -0.43, P < 0.01). The postprandial plasma glucose
      lowering efficacies was also significantly greater with DPP-4i/INS than with
      placebo/insulin (weighted mean difference -1.65 mmol/L, 95% CI: -2.34, -0.96, P <
      0.05). The risk of hypoglycemia or severe hypoglycemia was similar for DPP4i/INS
      and placebo/insulin treatments. There was no significant difference in the
      glycemia-lowering efficacy between DPP-4i/INS and alpha-glucosidase
      inhibitors/insulin, thiazolidinedione/insulin and glucagon-like peptide-1
      receptor agonist/insulin. Sodium-glucose cotransporter 2 inhibitor/insulin
      treatment achieved better placebo-corrected efficacy in lowering postprandial
      plasma glucose, with less weight gain and no higher risk of hypoglycemia.
      CONCLUSIONS: Treatment with DPP-4 inhibitors combined with insulin improved
      glycemic control without an increased risk of hypoglycemia or weight gain
      compared with insulin treatment alone.

PMID- 29047220
TI  - The cytokines and micro-environment of fracture haematoma: Current evidence.
AB  - Fracture haematoma formation is the first and foremost important stage of
      fracture healing. It orchestrates the inflammatory and cellular processes leading
      to the formation of callus and the restoration of the continuity of the bone.
      Evidence suggests that blocking this initial stage could lead to an impairment of
      the overall bone healing process. This review aims to analyse the existing
      evidence of molecular contributions to bone healing within fracture haematoma and
      to determine the potential to modify the molecular response to fracture in the
      haematoma with the aim of improving union times. A comprehensive search of
      literature documenting fracture haematoma cytokine content was performed.
      Suitable papers according to prespecified criteria were identified and analysed
      according to Preferred Reporting Items for Systematic Reviews and Meta-analyses
      guidelines. A total of 89 manuscripts formed the basis of this analysis. Low
      oxygen tension, high acidity, and high calcium characterised initially the
      fracture haematoma micro-environment. In addition, a number of cytokines have
      been measured with concentrations significantly higher than those found in
      peripheral circulation. Growth factors have also been isolated, with an observed
      increase in bone morphogenetic proteins, platelet-derived growth factor, and
      transforming growth factor. Although molecular modification of fracture haematoma
      has been attempted, more research is required to determine a suitable biological
      response modifier leading to therapeutic effects. The cytokine content of
      fracture haematoma gives insight into processes occurring in the initial stages
      of fracture healing. Manipulation of signalling molecules represents a promising
      pathway to target future therapies aiming to upregulate the osteogenesis.

PMID- 29047222
TI  - Validation of the German version of the Ford Insomnia Response to Stress Test.
AB  - The purpose of this study was to assess the psychometric properties of a German
      version of the Ford Insomnia Response to Stress Test with groups with and without
      sleep problems. Three studies were analysed. Data set 1 was based on an initial
      screening for a sleep training program (n = 393), data set 2 was based on a study
      to test the test-retest reliability of the Ford Insomnia Response to Stress Test
      (n = 284) and data set 3 was based on a study to examine the influence of
      competitive sport on sleep (n = 37). Data sets 1 and 2 were used to test internal
      consistency, factor structure, convergent validity, discriminant validity and
      test-retest reliability of the Ford Insomnia Response to Stress Test. Content
      validity was tested using data set 3. Cronbach's alpha of the Ford Insomnia
      Response to Stress Test was good (alpha = 0.80) and test-retest reliability was
      satisfactory (r = 0.72). Overall, the one-factor model showed the best fit.
      Furthermore, significant positive correlations between the Ford Insomnia Response
      to Stress Test and impaired sleep quality, depression and stress reactivity were
      in line with the expectations regarding the convergent validity. Subjects with
      sleep problems had significantly higher scores in the Ford Insomnia Response to
      Stress Test than subjects without sleep problems (P < 0.01). Competitive athletes
      with higher scores in the Ford Insomnia Response to Stress Test had significantly
      lower sleep quality (P = 0.01), demonstrating that vulnerability for stress
      induced sleep disturbances accompanies poorer sleep quality in stressful
      episodes. The findings show that the German version of the Ford Insomnia Response
      to Stress Test is a reliable and valid questionnaire to assess the vulnerability
      to stress-induced sleep disturbances.

PMID- 29047221
TI  - Selection and characterization of Bacillus thuringiensis strains from
      northwestern Himalayas toxic against Helicoverpa armigera.
AB  - In this study, we present the selection and the characterization of Bacillus
      thuringiensis (Bt) strains with respect to their cry/cyt gene content and
      toxicity evaluation toward one of the most important polyphagous lepidopteran
      pest, Helicoverpa armigera. Fifty-six Bt isolates were obtained from 10 different
      regions of northwestern Himalayas, recording a total B. thuringiensis index of
      0.62. Scanning electron microscopy revealed presence of bipyramidal, spherical,
      flat and irregular crystal shapes; SDS-PAGE analysis of spore-crystal mixtures
      showed the prominence of 130, 70, and 100 kDa protein bands in majority of the
      isolates; PCR analysis with primers for eight cry and cyt gene families and 13
      cry gene subfamilies resulted in isolates showing different combinations of
      insecticidal genes. Strains containing cry1 were the most abundant (57.1%)
      followed by cyt2 (46.42%), cry11 (37.5%), cry2 (28.57%), cry4 (21.42%), cyt1
      (19.64%), cry3 (8.9%), and cry7, 8 (7.14%). A total of 30.35% of the strains did
      not amplify with any of the primers used in this study. Median lethal
      concentration 50 (LC50 ) estimates of spore-crystal mixtures of Bt-JK12, 17, 22,
      48, and 72 against second instar larvae of H. armigera was observed to be 184.62,
      275.39, 256.29, 259.93 MUg ml-1 , respectively. B. thuringiensis presents great
      diversity with respect to the presence of crystal protein encoding genes and
      insecticidal activity. Four putative toxic isolates identified in this study have
      potential application in insect pest control. B. thuringiensis isolate JK12
      exhibited higher toxicity against H. armigera than that of B. thuringiensis HD1,
      hence can be commercially exploited to control insect pest for sustainable crop
      production. The results of this study confirm the significance of continuous
      exploration of new Bt stains from different ecological regions of the world.

PMID- 29047223
TI  - Regeneration of osteochondral defects in vivo by a cell-free cylindrical
      poly(lactide-co-glycolide) scaffold with a radially oriented microstructure.
AB  - A scaffold with an oriented porous architecture to facilitate cell infiltration
      and bioactive interflow between neo-host tissues is of great importance for in
      situ inductive osteochondral regeneration. In this study, a poly(lactide-co
      glycolide) (PLGA) scaffold with oriented pores in its radial direction was
      fabricated via unidirectional cooling of the PLGA solution in the radial
      direction, following with lyophilization. Micro-computed tomography evaluation
      and scanning electron microscopy observation confirmed the radially oriented
      microtubular pores in the scaffold. The scaffold had porosity larger than 90% and
      a compressive modulus of 4 MPa in a dry state. Culture of bone marrow stem cells
      in vitro revealed faster migration and regular distribution of cells in the
      poly(lactide-co-glycolide) scaffold with oriented pores compared with the random
      PLGA scaffold. The cell-free oriented macroporous PLGA scaffold was implanted
      into rabbit articular osteochondral defect in vivo for 12 weeks to evaluate its
      inductive tissue regeneration function. Histological analysis confirmed obvious
      tide mark formation and abundant chondrocytes distributed regularly with obvious
      lacunae in the cartilage layer. Safranin O-fast green staining showed an obvious
      boundary between the two layers with distinct staining results, indicating the
      simultaneous regeneration of the cartilage and subchondral bone layers, which is
      not the case for the random poly(lactide-co-glycolide) scaffold after the same
      implantation in vivo. The oriented macroporous PLGA scaffold is a promising
      material for the in situ inductive osteochondral regeneration without the
      necessity of preseeding cells.

PMID- 29047225
TI  - Understanding middle-aged and older adults' first associations with the word
      "cancer": A mixed methods study in England.
AB  - OBJECTIVE: Cancer is still widely feared and often associated with death.
      Fatalistic beliefs adversely affect help-seeking for cancer symptoms and
      engagement in cancer prevention. This study aims to understand middle-aged and
      older adults' first association with the word "cancer" and their relationship
      with sociodemographic factors, cancer fear, and cancer information avoidance.
      METHODS: We conducted a cross-sectional survey of 1464 community-based adults
      aged 50 to 70 living in England in April 2015. First associations with cancer
      were measured qualitatively and analysed using content analysis. We used binary
      logistic regression to analyse associations between the most common first
      association of cancer and sociodemographic characteristics, cancer fear, and
      cancer information avoidance. RESULTS: Cancer was most commonly associated with
      "death" (26%). Respondents with lower levels of education, living in the Midlands
      or North of England where cancer mortality is higher, or with close friends or
      family members with a cancer history, were more likely to associate cancer with
      death. Cancer fear was significantly associated with death associations, but
      cancer information avoidance was not. CONCLUSIONS: Despite improved cancer
      outcomes, middle-aged and older adults often associate cancer with death. Further
      efforts to decrease fatalistic associations in this age group may be needed.

PMID- 29047226
TI  - Babies in boxes and the missing links on safe sleep: Human evolution and cultural
      revolution.
AB  - Concerns about bedsharing as a risk for sudden infant death syndrome and other
      forms of sleep-associated infant death have gained prominence as a public health
      issue. Cardboard "baby boxes" are increasingly promoted to prevent infant death
      through separate sleep, despite no proof of efficacy. However, baby boxes disrupt
      "breastsleeping" (breastfeeding with co-sleeping) and may undermine
      breastfeeding. Recommendations enforcing separate sleep are based on 20th century
      Euro-American social norms for solitary infant sleep and scheduled feedings via
      bottles of cow's milk-based formula, in contrast to breastsleeping, an
      evolutionary adaptation facilitating the survival of mammalian infants for
      millennia. Interventions that aim to prevent bedsharing, such as the cardboard
      baby box, fail to consider the implications of evolutionary biology or of
      ethnocentrism in sleep guidance. Moreover, the focus on bedsharing neglects more
      potent risks such as smoking, drugs, alcohol, formula feeding, and poverty.
      Distribution of baby boxes may divert resources and attention away from
      addressing these other risk factors and lead to a false sense of security wherein
      we overlook that sudden unexplained infant deaths also occur in solitary sleep
      environments. Recognizing breastsleeping as the evolutionary and cross-cultural
      norm entails re-evaluating our research and policy priorities, such as providing
      greater structural support for families, supporting breastfeeding and safe co
      sleeping, investigating ways to safely minimize separation for formula-fed
      infants, and mitigating the potential harms of mother-infant separation when
      breastsleeping is disrupted. Resources would be better spent addressing such
      questions rather than on a feel-good solution such as the baby box.

PMID- 29047227
TI  - Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal
      cancer.
AB  - High rates of telomerase reverse transcriptase (TERT) promoter mutations have
      recently been described in urothelial carcinoma (UC). Unlike UC in the bladder,
      adenocarcinomas account for the majority of urachal cancer (UrC) cases. As data
      in UrC is unclear, we analyzed TERT promoter mutations in a large cohort of UrC
      for its differential diagnostic, clinicopathological and prognostic significance.
      UrC cases from six academic centers were analyzed for c.-146C>T (C250T) and c.
      124C>T (C228T) TERT promoter mutations by PCR and Sanger sequencing.
      Clinicopathological and survival data were collected. The cohort consisted of 15
      men (56%) and 12 women (44%) with a median age of 50 years including 23
      adenocarcinomas, two squamous cell carcinomas (SCC), one UC and one
      undifferentiated carcinoma. In one case of (mucinous) urachal adenocarcinoma a
      C228T mutation was detected (1/23; 4%), like in a case of SCC in addition to one
      C250T mutation in the UC case. TERT promoter mutations are very rare in urachal
      adenocarcinomas (unlike in UC) with differential diagnostic implications.
      Additionally, the low TERT promoter mutation rate in urachal adenocarcinomas is
      more comparable to colorectal adenocarcinomas than to UC, giving further support
      to recent genetic findings and therapeutic considerations.

PMID- 29047224
TI  - Ral signaling pathway in health and cancer.
AB  - The Ral (Ras-Like) signaling pathway plays an important role in the biology of
      cells. A plethora of effects is regulated by this signaling pathway and its
      prooncogenic effectors. Our team has demonstrated the overactivation of the RalA
      signaling pathway in a number of human malignancies including cancers of the
      liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors.
      Additionally, we have shown that the activation of RalA in cancer stem cells is
      higher in comparison with differentiated cancer cells. In this article, we review
      the role of Ral signaling in health and disease with a focus on the role of this
      multifunctional protein in the generation of therapies for cancer. An improved
      understanding of this pathway can lead to development of a novel class of
      anticancer therapies that functions on the basis of intervention with RalA or its
      downstream effectors.

PMID- 29047228
TI  - Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins
      within Cancer Cells.
AB  - Strongly luminescent iridium(III) complexes, [Ir(C,N)2 (S,S)]+ (1) and [Ir(C,N)2
      (O,O)] (2), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione)
      chelating ligands, have been characterized by X-ray crystallography and DFT
      calculations. Their long phosphorescence lifetimes in living cancer cells give
      rise to high quantum yields for the generation of 1 O2 , with large 2-photon
      absorption cross-sections. 2 is nontoxic to cells, but potently cytotoxic to
      cancer cells upon brief irradiation with low doses of visible light, and potent
      at sub-micromolar doses towards 3D multicellular tumor spheroids with 2-photon
      red light. Photoactivation causes oxidative damage to specific histidine residues
      in the key proteins in aldose reductase and heat-shock protein-70 within living
      cancer cells. The oxidative stress induced by iridium photosensitizers during
      photoactivation can increase the levels of enzymes involved in the glycolytic
      pathway.

PMID- 29047229
TI  - Enhanced inflammation and attenuated tumor suppressor pathways are associated
      with oncogene-induced lung tumors in aged mice.
AB  - Aging is often accompanied by a dramatic increase in cancer susceptibility. To
      gain insights into how aging affects tumor susceptibility, we generated a
      conditional mouse model in which oncogenic KrasG12D was activated specifically in
      lungs of young (3-5 months) and old (19-24 months) mice. Activation of KrasG12D
      in old mice resulted in shorter survival and development of higher-grade lung
      tumors. Six weeks after KrasG12D activation, old lung tissues contained higher
      numbers of adenomas than their young tissue counterparts. Lung tumors in old mice
      displayed higher proliferation rates, as well as attenuated DNA damage and p53
      tumor suppressor responses. Gene expression comparison of lung tumors from young
      and old mice revealed upregulation of extracellular matrix-related genes in young
      tumors, indicative of a robust cancer-associated fibroblast response. In old
      tumors, numerous inflammation-related genes such as Ccl7, IL-1beta, Cxcr6, and IL
      15ra were consistently upregulated. Increased numbers of immune cells were
      localized around the periphery of lung adenomas from old mice. Our experiments
      indicate that more aggressive lung tumor formation in older KrasG12D mice may be
      in part the result of subdued tumor suppressor and DNA damage responses, an
      enhanced inflammatory milieu, and a more accommodating tissue microenvironment.

PMID- 29047230
TI  - A comprehensive genome-wide analysis of long noncoding RNA expression profile in
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide,
      especially in East Asia and China. Long noncoding RNAs (lncRNAs) are emerging as
      critical regulators that may be involved in the development and progression of
      cancers in humans. However, the contributions of lncRNAs to HCC development,
      metastasis, and recurrence remain largely unknown. In this study, we
      comprehensively investigated lncRNA expression profile in HCC and normal tissues
      using TCGA RNA sequencing data, one RNA sequencing dataset, and two microarray
      datasets from GEO. By analyzing these four datasets, we identified hundreds of
      expression-dysregulated lncRNAs in HCC tissues compared with normal tissues.
      Genomic copy number variation analysis showed that many of those lncRNAs disorder
      are related to the copy number amplification or deletion. Moreover, several
      lncRNAs expression levels are associated with HCC patients' overall and
      recurrence-free survival, such as RP1-228H13.5, TMCC1-AS1, LINC00205, and RP11
      307C12.11. Furthermore, we identified two lncRNAs termed PVT1 and SNHG7 that may
      be involved in HCC cells metastasis by comparing lncRNAs expression profiles
      between early recurrence HCC tissues with metastasis and late recurrence HCC
      tissues without metastasis. Finally, loss-of-function assays confirmed that
      knockdown of SNHG7 and PVT1 impaired HCC cells invasion. Taken together, these
      findings may provide a valuable resource for further identification of novel
      biomarkers and therapeutic targets for HCC patients.

PMID- 29047231
TI  - Alterations in Gut Microbiota and Immunity by Dietary Fat.
AB  - Gut microbiota play critical physiological roles in energy extraction from the
      intestine and in the control of systemic immunity, as well as local intestinal
      immunity. Disturbance of gut microbiota leads to the development of several
      diseases, such as colitis, inflammatory bowel diseases, metabolic disorders,
      cancer, etc. From a metabolic point of view, the gut is a large metabolic organ
      and one of the first to come into contact with dietary fats. Interestingly,
      excessive dietary fat has been incriminated as a primary culprit of metabolic
      syndrome and obesity. After intake of high-fat diet or Western diet, extensive
      changes in gut microbiota have been observed, which may be an underlying cause of
      alterations in whole body metabolism and nutrient homeostasis. Here, we summarize
      recent data on changes in the gut microbiota and immunity associated with dietary
      fat, as well as their relationships with the pathogenesis of metabolic syndrome.
      These findings may provide insight into the understanding of the complex
      pathophysiology related to the development of metabolic diseases and offer an
      opportunity to develop novel candidates for therapeutic agents.

PMID- 29047232
TI  - Knockdown of Long Non-Coding RNA NEAT1 Inhibits Proliferation and Invasion and
      Induces Apoptosis of Osteosarcoma by Inhibiting miR-194 Expression.
AB  - PURPOSE: Long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1
      (NEAT1) has been implicated as an oncogene in the development and progression of
      osteosarcoma. This study aims to explore the mechanism of NEAT1 in osteosarcoma.
      MATERIALS AND METHODS: Expressions of NEAT1 and miR-194 in osteosarcoma tissues
      and cells were detected by quantitative real-time PCR. The effects of NEAT1
      knockdown or miR-194 overexpression on cell proliferation, invasion, and
      apoptosis were determined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl
      tetrazolium bromide (MTT) assay, transwell invasive assay, and flow cytometry
      analysis, respectively. Luciferase reporter assay was performed to observe the
      possible interaction between NEAT1 and miR-194. RESULTS: NEAT1 was upregulated
      and miR-194 was downregulated in osteosarcoma tissues and cells. Knockdown of
      NEAT1 or overexpression of miR-194 suppressed proliferation and invasion and
      induced apoptosis of osteosarcoma cells in vitro. Luciferase reporter assay
      validated that NEAT1 could interact with miR-194 and negatively modulated its
      expression. Furthermore, inhibition of miR-194 reversed the suppression of
      proliferation and invasion and the promotion of apoptosis induced by NEAT1
      depletion in osteosarcoma cells. CONCLUSION: Knockdown of NEAT1 suppressed
      proliferation and invasion and induced apoptosis in osteosarcoma cells by
      inhibiting miR-194 expression.

PMID- 29047233
TI  - Overexpression of miR-191 Predicts Poor Prognosis and Promotes Proliferation and
      Invasion in Esophageal Squamous Cell Carcinoma.
AB  - PURPOSE: Accumulating evidence has shown that dysregulation of microRNA-191 (miR
      191) is closely associated with tumorigenesis and progression in a wide range of
      cancers. This study aimed to explore the potential role of miR-191 in esophageal
      squamous cell carcinoma (ESCC). MATERIALS AND METHODS: miR-191 expression was
      assessed in 93 ESCC tissue specimens by real-time polymerase chain reaction, and
      survival analysis was performed via Kaplan-Meier and Cox regression analyses. 3
      (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, plate colony
      forming, BrdU, and Transwell assays were conducted to observe the effect of miR
      191 on ESCC proliferation and invasion. Luciferase reporter and western blot
      assays were taken to identify target genes of miR-191. RESULTS: miR-191 was
      overexpressed in 93 cases of ESCC, compared with adjacent normal tissues, and miR
      191 expression was significantly related to differentiation, depth of invasion,
      TNM stage, lymph node metastasis, and distant metastasis of tumor. Kaplan-Meier
      and Cox regression analyses demonstrated that overexpression of miR-191 was an
      independent and significant predictor of ESCC prognosis. Both gain-of-function
      and loss-of-function experiments showed that miR-191 promoted ESCC cell
      proliferation and invasion activities in vitro. Early growth response 1 (EGR1), a
      tumor suppressor, was predicted as a direct target of miR-191. Luciferase
      reporter and western blot assays proved that miR-191 reduced EGR1 expression by
      directly binding its 3' untranslated region. Moreover, EGR1 knockdown by siRNA
      enhanced ESCC cell growth and invasion. CONCLUSION: Our findings provide specific
      biological roles of miR-191 in ESCC survival and progression. Targeting the novel
      miR-191/EGR1 axis represents a potential new therapeutic way to block ESCC
      development.

PMID- 29047234
TI  - Lung Cancer Risk and Residential Exposure to Air Pollution: A Korean Population
      Based Case-Control Study.
AB  - PURPOSE: To investigate the association between long-term exposure to ambient air
      pollution and lung cancer incidence in Koreans. MATERIALS AND METHODS: This was a
      population-based case-control study covering 908 lung cancer patients and 908
      controls selected from a random sample of people within each Korean province and
      matched according to age, sex, and smoking status. We developed land-use
      regression models to estimate annual residential exposure to particulate matter
      (PM10) and nitrogen dioxide (NO2) over a 20-year exposure period. Logistic
      regression was used to estimate odds ratios (ORs) and their corresponding 95%
      confidence intervals (CI). RESULTS: Increases in lung cancer incidence (expressed
      as adjusted OR) were 1.09 (95% CI: 0.96-1.23) with a ten-unit increase in PM10
      (MUg/m3) and 1.10 (95% CI: 1.00-1.22) with a ten-unit increase in NO2 (ppb).
      Tendencies for stronger associations between air pollution and lung cancer
      incidence were noted among never smokers, among those with low fruit consumption,
      and among those with a higher education level. Air pollution was more strongly
      associated with squamous cell and small cell carcinomas than with adenocarcinoma
      of the lung. CONCLUSION: This study provides evidence that PM10 and NO2
      contribute to lung cancer incidence in Korea.

PMID- 29047235
TI  - Gender Difference in the Long-Term Clinical Implications of New-Onset Atrial
      Fibrillation after Coronary Artery Bypass Grafting.
AB  - PURPOSE: New-onset postoperative atrial fibrillation (POAF) is associated with
      poor short- and long-term outcomes after isolated coronary artery bypass graft
      (CABG) surgery. This study evaluated gender differences in the long-term clinical
      implications of POAF. MATERIALS AND METHODS: After propensity score matching, a
      gender-based comparison of long-term (>1 year) newly developed atrial
      fibrillation (LTAF) and mortality between 1664 (480 females) consecutive patients
      with (POAF) and without POAF (no-POAF) who had undergone CABG was performed.
      RESULTS: During a follow-up of 49+/-28 months, cumulative survival free of LTAF
      was lower in the POAF group than in the no-POAF group for both males (92.1% vs.
      98.2%, p<0.001) and females (84.1% vs. 98.0%, p<0.001). However, female patients
      with POAF more frequently developed LTAF than male POAF patients (13.9 % vs.
      6.9%, p=0.049). In multivariate analysis, POAF was a significant predictor of
      LTAF among males [hazard ratio (HR) 4.91; 95% confidence interval (CI) 1.22
      19.79, p=0.031] and females (HR 16.50; 95% CI 4.79-56.78; p<0.001). POAF was a
      predictor of long-term mortality among females (adjusted HR 3.96; 95% CI 1.13
      13.87, p=0.033), but not among males. CONCLUSION: Although POAF was related to
      LTAF in both genders, cumulative survival free of LTAF was poorer among females
      than among males. Additionally, a significant correlation with long-term
      mortality after CABG was observed among female patients with POAF.

PMID- 29047236
TI  - Subsequent Thrombotic Outcomes in Patients with Ischemic Stroke with
      Antiphospholipid Antibody Positivity.
AB  - PURPOSE: International consensus criteria for antiphospholipid syndrome (APS)
      require persistently positive antiphospholipid antibodies (aPL) and medium or
      high titers in association with clinical manifestations. However, the clinical
      relevance of persistence and titers of aPL in patients with stroke has not been
      identified. We aimed to investigate the risk of subsequent thrombotic events in
      patients with ischemic stroke with aPL positivity in terms of aPL status.
      MATERIALS AND METHODS: We reviewed the medical records of 99 patients with
      ischemic stroke with at least one or more aPL-positivity (i.e., positivity for
      aCL, anti-beta2-glycoprotein-1, and/or lupus anticoagulants). The patients were
      divided into two groups: "definite APS" who fulfilled the laboratory criteria and
      "indefinite APS" who fell short of the criteria. We compared the risk of
      subsequent thrombotic events between the two groups. Cox proportional hazards
      model and Kaplan-Meier survival curves were used for the analyses. RESULTS: Of
      the 99 patients, 46 (46%) were classified as having definite APS and 53 (54%) as
      having indefinite APS. The mean follow-up was 51.6 months. Overall event numbers
      were 14 (30.4%) in definite APS and 16 (30.2%) in indefinite APS. Increased
      subsequent thrombotic events (hazard ratio 1.039; 95% confidence interval 0.449
      2.404; p=0.930) and decreased time to thrombotic events (log-rank p=0.321) were
      not associated with aPL status. CONCLUSION: There was no increased risk of
      subsequent thrombotic events in ischemic stroke patients with definite APS,
      compared with those with indefinite APS.

PMID- 29047237
TI  - Proteus vulgaris and Proteus mirabilis Decrease Candida albicans Biofilm
      Formation by Suppressing Morphological Transition to Its Hyphal Form.
AB  - PURPOSE: Candida albicans (C. albicans) and Proteus species are causative agents
      in a variety of opportunistic nosocomial infections, and their ability to form
      biofilms is known to be a virulence factor. In this study, the influence of co
      cultivation with Proteus vulgaris (P. vulgaris) and Proteus mirabilis (P.
      mirabilis) on C. albicans biofilm formation and its underlying mechanisms were
      examined. MATERIALS AND METHODS: XTT reduction assays were adopted to measure
      biofilm formation, and viable colony counts were performed to quantify yeast
      growth. Real-time reverse transcriptase polymerase chain reaction was used to
      evaluate the expression of yeast-specific genes (rhd1 and rbe1), filament
      formation inhibiting genes (tup1 and nrg1), and hyphae-related genes (als3, ece1,
      hwp1, and sap5). RESULTS: Candida biofilm formation was markedly inhibited by
      treatment with either living or heat-killed P. vulgaris and P. mirabilis. Proteus
      cultured supernatant also inhibited Candida biofilm formation. Likewise,
      treatment with live P. vulgaris or P. mirabilis or with Proteus-cultured
      supernatant decreased expression of hyphae-related C. albicans genes, while the
      expression of yeast-specific genes and the filament formation inhibiting genes of
      C. albicans were increased. Heat-killed P. vulgaris and P. mirabilis treatment,
      however, did not affect the expression of C. albicans morphology-related genes.
      CONCLUSION: These results suggest that secretory products from P. vulgaris and P.
      mirabilis regulate the expression of genes related to morphologic changes in C.
      albicans such that transition from the yeast form to the hyphal form can be
      inhibited.

PMID- 29047238
TI  - Identification of 10 Candidate Biomarkers Distinguishing Tuberculous and
      Malignant Pleural Fluid by Proteomic Methods.
AB  - PURPOSE: Pleural effusion, an accumulation of fluid in the pleural space, usually
      occurs in patients when the rate of fluid formation exceeds the rate of fluid
      removal. The differential diagnosis of tuberculous pleurisy and malignant pleural
      effusion is a difficult task in high tuberculous prevalence areas. The aim of the
      present study was to identify novel biomarkers for the diagnosis of pleural fluid
      using proteomics technology. MATERIALS AND METHODS: We used samples from five
      patients with transudative pleural effusions for internal standard, five patients
      with tuberculous pleurisy, and the same numbers of patients having malignant
      effusions were enrolled in the study. We analyzed the proteins in pleural fluid
      from patients using a technique that combined two-dimensional liquid-phase
      electrophoresis and matrix assisted laser desorption/ionization-time of flight
      mass spectrometry. RESULTS: We identified a total of 10 proteins with statistical
      significance. Among 10 proteins, trasthyretin, haptoglobin, metastasis-associated
      protein 1, t-complex protein 1, and fibroblast growth factor-binding protein 1
      were related with malignant pleural effusions and human ceruloplasmin, lysozyme
      precursor, gelsolin, clusterin C complement lysis inhibitor, and peroxirexdoxin 3
      were expressed several times or more in tuberculous pleural effusions.
      CONCLUSION: Highly expressed proteins in malignant pleural effusion were
      associated with carcinogenesis and cell growth, and proteins associated with
      tuberculous pleural effusion played a role in the response to inflammation and
      fibrosis. These findings will aid in the development of novel diagnostic tools
      for tuberculous pleurisy and malignant pleural effusion of lung cancer.

PMID- 29047239
TI  - A Gender-Specific Association between Self-Reported Snoring and Hemoglobin A1c
      Levels in a General Population without Type 2 Diabetes Mellitus.
AB  - PURPOSE: We explored whether a gender difference was evident in terms of the
      associations of snoring with hemoglobin A1c (HbA1c) and homeostatic model
      assessment-insulin resistance (HOMA-IR) levels in a healthy population without
      type 2 diabetes mellitus (DM). MATERIALS AND METHODS: We analyzed 2706 males and
      4080 females who participated in the baseline survey of the Namwon Study. In
      terms of self-reported snoring frequency, participants were classified as non
      snorers or occasional (1-3 days/week), frequent (4-6 days/week), or constant (7
      days/week) snorers. Participants with DM, defined as a fasting blood glucose
      level >=126 mg/dL and/or use of insulin or hypoglycemic medication, were excluded
      from the analysis. RESULTS: In females, the fully adjusted mean (95% confidence
      interval) HbA1c levels in non-snorers and in occasional, frequent, and constant
      snorers were 5.53% (5.47-5.59%), 5.53% (5.47-5.59%), 5.57% (5.49-5.64%), and
      5.57% (5.51-5.64%), respectively, reflecting a dose-response relationship (p
      trend=0.004). Compared with female non-snorers, the risk of an elevated HbA1c
      level (top quintile, >=5.9%) in constant snorers remained significant (odds ratio
      1.30, 95% confidence interval 1.02-1.66) after full adjustment. In addition, in
      females, a significant linear trend in HbA1c level odds ratio by increased
      snoring frequency was apparent (p trend=0.019 in model 3). In contrast, no
      significant association between snoring frequency and HbA1c level was identified
      in males. No significant association between snoring frequency and HOMA-IR was
      detected in either gender. CONCLUSION: We discovered a gender-specific
      association between snoring and HbA1c level in a healthy, community-dwelling
      population free of DM.

PMID- 29047240
TI  - Identification and Functional Characterization of ST3GAL5 and ST8SIA1 Variants in
      Patients with Thyroid-Associated Ophthalmopathy.
AB  - PURPOSE: This study was conducted to identify and to functionally characterize
      genetic variants in ST3GAL5 and ST8SIA1 in Korean patients with thyroid
      associated ophthalmopathy (TAO). MATERIALS AND METHODS: Genetic analyses were
      conducted using DNA samples from TAO patients (n=50) and healthy subjects (n=48)
      to identify TAO-specific genetic variants of ST3GAL5 or ST8SIA1. The effect of
      each genetic variant on the transcription or expression of these genes was
      examined. Additionally, correlations between functional haplotypes of ST3GAL5 or
      ST8SIA1 and clinical characteristics of the patients were investigated. RESULTS:
      Six promoter variants and one nonsynonymous variant of ST3GAL5 were identified,
      and four major promoter haplotypes were assembled. Additionally, three promoter
      variants and two major haplotypes of ST8SIA1 were identified. All ST3GAL5 and
      ST8SIA1 variants identified in TAO patients were also found in healthy controls.
      Promoter activity was significantly decreased in three promoter haplotypes of
      ST3GAL5 and increased in one promoter haplotype of ST8SIA1. Transcription factors
      activating protein-1, NKX3.1, and specificity protein 1 were revealed as having
      roles in transcriptional regulation of these haplotypes. The nonsynonymous
      variant of ST3GAL5, H104R, did not alter the expression of ST3GAL5. While no
      differences in clinical characteristics were detected in patients possessing the
      functional promoter haplotypes of ST3GAL5, exophthalmic values were significantly
      lower in patients with the ST8SIA1 haplotype, which showed a significant increase
      in promoter activity. CONCLUSION: These results from genotype-phenotype analysis
      might suggest a possible link between the ST8SIA1 functional promoter haplotype
      and the clinical severity of TAO. However, further studies with larger sample
      sizes are warranted.

PMID- 29047241
TI  - Normative Values of Physical Examinations Commonly Used for Cerebral Palsy.
AB  - PURPOSE: The aim of this study was to establish normative values and to identify
      age-related change in physical examinations that are commonly used while
      evaluating patients with cerebral palsy (CP). MATERIALS AND METHODS: One hundred
      four healthy volunteers (mean age 36 years, standard deviation 15 years) were
      enrolled and divided into four age groups: 13-20, 21-35, 36-50, and 51 years and
      older. The eighteen physical examination tests for CP were selected by five
      orthopedic surgeons in consensus-building session. The measurements were taken by
      three orthopedic surgeons. RESULTS: There was no significant difference in the
      measures of physical examination among all the age groups, except for the Staheli
      test (p=0.002). The post hoc test revealed that the mean hip extension was 2.7
      degrees  higher in the 13-20-year-old group than in the other age groups. The
      bilateral popliteal angle had a tendency to increase in those over 36-years-old.
      There were 31 participants (30%) with a unilateral popliteal angle greater than
      40 degrees . CONCLUSION: We documented normative values that can be widely used
      for evaluating CP in patients 13 years and older.

PMID- 29047242
TI  - Effect of Sagittal Balance on Risk of Falling after Lateral Lumbar Interbody
      Fusion Surgery Combined with Posterior Surgery.
AB  - PURPOSE: To demonstrate the impact of correcting sagittal balance (SB) on
      functional outcomes of surgical treatment for degenerative spinal disease and
      actual falls via utilization of new minimally invasive lumbar fusion techniques
      via a lateral approach. MATERIALS AND METHODS: From November 2011 to March 2015,
      we enrolled 56 patients who underwent minimally invasive lateral lumbar interbody
      fusion (LLIF) and matched 112 patients receiving decompression/postero-lateral
      fusion (PLF) surgery for lumbar spinal stenosis. According to SB status using C7
      plumb line-distance (C7PL) and surgery type, patients were divided into three
      groups: SB PLF, sagittal imbalance (SI) PLF, and LLIF groups. We then compared
      their outcomes. RESULTS: The mean C7PL was 6.2+/-13.6 mm in the SB PLF group,
      72.9+/-33.8 mm in the SI PLF group, and 74.8+/-38.2 mm in the LLIF group
      preoperatively. Postoperatively, C7PL in only the LLIF group improved
      significantly (p=0.000). Patients in the LLIF group showed greater improvement in
      fall-related functional test scores than the SI PLF group (p=0.007 for Alternate
      Step test, p=0.032 for Sit-to-Stand test). The average number of postoperative
      falls was 0.4+/-0.7 in the SB PLF group, 1.1+/-1.4 in the SI PLF group, and 0.8+/
      1.0 in the LLIF group (p=0.041). Oswestry Disability Index and the Euro-QoL 5
      dimension visual analogue scale scores also showed greater improvements in the
      LLIF group than in the SI PLF group at postoperative 1 year (p=0.003, 0.016).
      CONCLUSION: Surgical correction of SI in patients with lumbar spinal stenosis
      using a combination of minimal invasive LLIF and posterior surgery achieved
      better surgical outcomes and a lower incidence of actual falls than PLF surgery.

PMID- 29047243
TI  - Three-Dimensional Fast Spin-Echo Imaging without Fat Suppression of the Knee:
      Diagnostic Accuracy Comparison to Fat-Suppressed Imaging on 1.5T MRI.
AB  - PURPOSE: To evaluate the diagnostic performance of three-dimensional fast spin
      echo (3D FSE-Cube) without fat suppression (NFS) for detecting knee lesions,
      using comparison to 3D FSE-Cube with fat suppression (FS). MATERIALS AND METHODS:
      One hundred twenty-four patients who underwent 1.5T knee magnetic resonance
      imaging (MRI) scans and 25 subsequent arthroscopic surgeries were retrospectively
      reviewed. Using arthroscopic results and two-dimensional images as reference
      standards, diagnostic performances of 3D FSE-Cube-NFS and FS imaging about
      lesions of ligament, meniscus, subchondral bone marrow edema (BME), and cartilage
      were compared. Scan parameters of 3D FSE-Cube imaging were previously optimized
      by a porcine knee phantom. RESULTS: No significant differences were observed
      between detection rates of NFS and FS imaging for detecting lesions of meniscus
      and cartilage (p>0.05). However, NFS imaging had lower sensitivity for detection
      of medial collateral ligament (MCL) tears, and lower sensitivity and specificity
      for detection of BME lesions, compared to FS imaging (p<0.05). CONCLUSION: 3D FSE
      Cube-NFS imaging showed similar diagnostic performance for detecting lesions of
      meniscus or cartilage compared to FS imaging, unlike MCL or BME lesions.

PMID- 29047245
TI  - 11beta-Hydroxysteroid Dehydrogenase Type 1 Inhibition Attenuates the Adverse
      Effects of Glucocorticoids on Dermal Papilla Cells.
AB  - PURPOSE: Glucocorticoids, stress-related hormones, inhibit hair growth.
      Intracellular glucocorticoid availability is regulated by 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 was recently detected in
      keratinocytes and fibroblasts. However, the expression of 11beta-HSD1 in human
      hair follicles remains unknown. We aimed to examine 11beta-HSD1 expression in
      human dermal papilla cells (DPCs) and to investigate whether modulation of 11beta
      HSD1 activity can regulate the negative effects of glucocorticoids on DPCs.
      MATERIALS AND METHODS: 11beta-HSD1 expression in normal human scalp skin was
      examined by immunohistochemistry. 11beta-HSD1 protein was detected in Western
      blots of human DPCs. Cultured human DPCs were treated with cortisol with or
      without a selective 11beta-HSD1 inhibitor and subsequently stained for Ki-67
      antibody. Expression levels of 11beta-HSD1, Wnt5a, alkaline phosphatase (ALP),
      and vascular endothelial growth factor (VEGF) were analyzed by Western blotting.
      RESULTS: 11beta-HSD1 was detected in dermal papilla in human scalp skin by
      immunohistochemistry. Human DPCs expressed 11beta-HSD1 protein in vitro.
      Furthermore, cortisol stimulated the expression of 11beta-HSD1 in DPCs.
      Glucocorticoids decreased cellular proliferation and the expression of Wnt5a,
      ALP, and VEGF in DPCs. A specific 11beta-HSD1 inhibitor significantly attenuated
      the anti-proliferative effects of cortisol and reversed the cortisol-induced
      suppression of Wnt5a, ALP, and VEGF expression in DPCs. CONCLUSION: Our data
      demonstrated the expression of 11beta-HSD1 in human DPCs and revealed that
      inhibition of 11beta-HSD1 activity can partially prevent the negative effect of
      glucocorticoids on DPCs, suggesting the possible application of 11beta-HSD1
      inhibitors for stress-related hair loss.

PMID- 29047244
TI  - Effects of Autologous Platelet-Rich Plasma on Regeneration of Damaged Endometrium
      in Female Rats.
AB  - PURPOSE: To investigate whether autologous platelet-rich plasma (PRP) treatment
      can improve regeneration of the endometrium in an experimental model of ethanol
      induced damage. MATERIALS AND METHODS: Sixty female Sprague-Dawley rats were
      randomly assigned into three groups: control group, ethanol group, and PRP
      treated group (administration of 0.25 mL of PRP into both uterine cavities 72
      hours after ethanol injection). After 15 days of endometrial damage, all the
      animals were sacrificed during the estrous cycle, and samples were taken from the
      mid-uterine horn. Functional and structural recovery of the endometrium was
      analyzed by hematoxylin-eosin (H&E) and Masson trichrome (MT) staining, real-time
      polymerase chain reaction (PCR) assay, and immuno-histochemical (IHC) analyses.
      RESULTS: H&E and MT staining confirmed significantly decreased fibrosis and
      increased cellular proliferation in the PRP-treated group, compared to the
      ethanol group. The endometrial areas in the ethanol and PRP-treated groups were
      212.83+/-15.84 MUm2 and 262.34+/-12.33 MUm2 (p=0.065). Significantly stronger IHC
      expression of cytokeratin, homeobox A10 (HOXA10), vascular endothelial growth
      factor (VEGF), and Ki-67 was found in the PRP-treated group, compared to the
      ethanol group. In real-time PCR analyses, interleukin-1beta mRNA was down
      regulated, while c-Kit mRNA was up-regulated, in the PRP-treated group, compared
      to the ethanol group. CONCLUSION: Intrauterine administration of autologous PRP
      stimulated and accelerated regeneration of the endometrium and also decreased
      fibrosis in a murine model of damaged endometrium.

PMID- 29047246
TI  - Social Support as a Mediator of Posttraumatic Embitterment and Perceptions of
      Meaning in Life among Danwon Survivors of the Sewol Ferry Disaster.
AB  - PURPOSE: Our research was designed to test and explore the relationships among
      embitterment, social support, and perceptions of meaning in life in the Danwon
      High School survivors of the Sewol ferry disaster. MATERIALS AND METHODS: Seventy
      five Sewol ferry disaster survivors were eligible for participation, and were
      invited to participate in the study 28 months after the disaster. Forty-eight
      (64%) survivors (24 males, 24 females) completed questionnaires; the
      Posttraumatic Embitterment Disorder (PTED) scale, the Functional Social Support
      Questionnaire (FSSQ), and the Meaning in Life Questionnaire (MLQ). RESULTS: PTED
      scores were negatively correlated with scores on the FSSQ and the Presence of
      Meaning (MLQ-P) (r=-0.43 and -0.40, respectively). The hierarchical regression
      analysis showed that FSSQ scores may fully mediate the effects of PTED scores on
      MLQ-P scores, given that the indirect effect was significant whereas the direct
      effect was not (95% confidence interval=-0.5912 to -0.0365). CONCLUSION: These
      findings imply that therapies targeting embitterment may play a vital role in
      increasing positive cognitions, such as those related to perceived social support
      and the meaningfulness of life.

PMID- 29047247
TI  - A Simulation Study of Propofol Effect-Site Concentration for Appropriate Sedation
      in Pediatric Patients Undergoing Brain MRI: Pharmacodynamic Analysis.
AB  - PURPOSE: We aimed to establish the propofol effect-site concentration (Ce) for
      appropriate sedation by pharmacodynamic analysis and to determine the propofol Ce
      during occurrence of sedation-related side effects in pediatric patients
      undergoing brain magnetic resonance imaging (MRI). MATERIALS AND METHODS: In 50
      pediatric patients scheduled for brain MRI, sedation was induced with 2.0 mg/kg
      propofol; additional propofol doses were 0.5-1 mg/kg. Propofol Ce was simulated
      by inputting the propofol administration profiles of patients into a pediatric
      compartmental model (Choi model). The relationship between propofol Ce and
      probabilities of sedation and recovery were analyzed using a sigmoidal Emax
      model. The simulated propofol Ce for sedation-related side effects was
      investigated. Population model parameters were estimated using the Nonlinear
      Mixed-Effects Modelling software. RESULTS: The mean values of propofol Ce50 for
      sedation during the preparation, scanning, and recovery phases were 1.23, 0.43,
      and 0.39 MUg/mL. The simulated propofol Ce values during oxygen desaturation
      (SpO2 <90%) (3 patients; 6%), hypotension (16 patients; 32%), and bradycardia (12
      patients; 24%) were 3.01+/-0.04, 2.05+/-0.63, and 2.41+/-0.89 MUg/mL,
      respectively. CONCLUSION: The required propofol Ce50 for applying monitors during
      the preparation phase before the start of MRI was higher than the propofol Ce50
      required during the scanning phase. During low-intensity stimulation phases, such
      as scanning, propofol bolus dose should be strictly titrated not to exceed the
      propofol Ce that can lead to oxygen desaturation because of the relatively low
      propofol Ce (Ce95, 1.43 MUg/mL) required for sedation in most patients.

PMID- 29047248
TI  - Association between Sleep Duration and Injury from Falling among Older Adults: A
      Cross-Sectional Analysis of Korean Community Health Survey Data.
AB  - PURPOSE: While sleeping problems increase with advancing age, there are inherent
      differences in sleep between males and females. Previous studies have shown
      inconsistent results of the relationship between sleep duration and risk of
      injury from falling. While controlling various sociodemographic and health
      related factors, national representative data were used in order to analyze the
      association between sleep duration and injury from falling among older adults.
      MATERIALS AND METHODS: The data were obtained from the Korean Community Health
      Survey of 2011. A total of 55654 individuals aged 65 years and older participated
      in the study. Multivariable logistic regression analysis was conducted to
      identify the factors associated with injury from falling. RESULTS: After
      adjusting for covariates, such as age, sex, marital status, whether or not an
      individual is a recipient of benefits from the National Basic Livelihood Act,
      hypertension, diabetes mellitus, dyslipidemia, stress level, and self-rated
      health status, those who slept five hours or less per day [odds ratio (OR)=1.26;
      95% confidence interval (CI)=1.18-1.34; p<0.001] or eight hours or more per day
      (OR=1.11; 95% CI=1.04-1.17; p=0.001) presented significantly higher ORs for
      injury from falling. A similar result was found when we conducted stratification
      by sex. CONCLUSION: The current study supports that there is a relationship
      between short sleep duration and injury from falling and also identified a
      marginal risk of long sleep in older adults. Therefore, sleep management in older
      adults with inadequate sleep duration may be necessary.

PMID- 29047249
TI  - A Personalized and Learning Approach for Identifying Drugs with Adverse Events.
AB  - PURPOSE: Adverse drug events (ADEs) are associated with high health and financial
      costs and have increased as more elderly patients treated with multiple
      medications emerge in an aging society. It has thus become challenging for
      physicians to identify drugs causing adverse events. This study proposes a novel
      approach that can improve clinical decision making with recommendations on ADE
      causative drugs based on patient information, drug information, and previous ADE
      cases. MATERIALS AND METHODS: We introduce a personalized and learning approach
      for detecting drugs with a specific adverse event, where recommendations tailored
      to each patient are generated using data mining techniques. Recommendations could
      be improved by learning the associations of patients and ADEs as more ADE cases
      are accumulated through iterations. After consulting the system-generated
      recommendations, a physician can alter prescriptions accordingly and report
      feedback, enabling the system to evolve with actual causal relationships.
      RESULTS: A prototype system is developed using ADE cases reported over 1.5 years
      and recommendations obtained from decision tree analysis are validated by
      physicians. Two representative cases demonstrate that the personalized
      recommendations could contribute to more prompt and accurate responses to ADEs.
      CONCLUSION: The current system where the information of individual drugs exists
      but is not organized in such a way that facilitates the extraction of relevant
      information together can be complemented with the proposed approach to enhance
      the treatment of patients with ADEs. Our illustrative results show the promise of
      the proposed system and further studies are expected to validate its performance
      with quantitative measures.

PMID- 29047250
TI  - Simultaneous Closure of a Left Atrial Appendage through an Atrial Septal Defect
      and the Atrial Septal Defect.
AB  - Left atrial appendage (LAA) occlusion can be employed as an alternative treatment
      to oral anticoagulation in patients with atrial fibrillation to prevent embolic
      events. Atrial septal defect (ASD) may be related with right heart dysfunction
      and allow paradoxical embolism to occur. However, occlusion of both LAA through
      atrial access with ostium secundum ASD and ASD in the same setting is unusual.
      Therefore, we report a case in which a LAA and an ASD was sequentially occluded.

PMID- 29047251
TI  - A Novel 1.13 Mb Interstitial Duplication at 19q13.32 Causing Developmental Delay
      and Microcephaly in a Pediatric Patient: the First Asian Case Reports.
AB  - Only 6 patients with partial trisomy of the long arm of chromosome 19 (19q),
      caused by direct interstitial duplications, have been reported until today.
      Herein, we report a pediatric patient with a novel 1.13 Mb direct interstitial
      duplication within 19q13.32, which is the smallest fragment affected so far. A
      five-year old Korean boy of healthy parents presented with microcephaly, growth
      retardation, developmental delay, and craniofacial dysmorphism. Even though G
      banded chromosome analysis at resolution of 550-band revealed normal karyotype,
      duplication of 1.13 Mb fragment within 19q13.32 was detected by array comparative
      genomic hybridization. Comparing with previously reported patients with pure
      duplication involving 19q as a sole chromosomal abnormality, our case showed the
      smallest duplication segment with relatively mild degree of clinical features.
      Our present case might serve as the landmark case among patients with 19q
      duplication for genotype-phenotype correlation study and further identification
      of critical region for 19q duplication abnormalities.

PMID- 29047252
TI  - Calcium Hydroxylapatite Pulmonary Embolism after Percutaneous Injection
      Laryngoplasty.
AB  - Injection medialization laryngoplasty is a procedure that has many advantages in
      treating vocal fold paralysis; however, undesired complications can occur. We
      experienced a case of a pulmonary embolism, suspected in a patient who had
      undergone an injection laryngoplasty with calcium hydroxylapatite (CaHA). The
      patient suffered dyspnea after undergoing the injection laryngoplasty. Chest
      embolism computed tomography (CT) scan revealed a new lesion of enhancing
      materials at the pulmonary vasculature in the right upper lobe. The CaHA embolism
      was suspected, and the patient was treated with warfarin for 12 months. The
      patient's symptom of dyspnea nearly disappeared and a follow up chest embolism CT
      scan revealed no signs of the previous lesion. Thus, we would like to report this
      rare case along with a review of the literature.

PMID- 29047253
TI  - Percutaneous Drainage and Povidone-Iodine Sclerotherapy of Cervical Lymphatic
      Malformation.
AB  - Lymphatic malformations in cases with macrocystic lesions can be treated with
      surgical excision or sclerotherapy using alcohol, bleomycin, doxycycline, or OK
      432. We report a case of a 24-year-old woman who underwent percutaneous drainage
      and povidone-iodine sclerotherapy as primary treatment for cervical lymphatic
      malformation. The patient underwent povidone-iodine sclerotherapy for 3
      consecutive days. After 8 months, ultrasonography of the lesion in the neck
      revealed complete resolution of the cervical lymphatic malformation without any
      complication. Povidone-iodine sclerotherapy can be a safe and cost-effective
      treatment option for cervical lymphatic malformation.

PMID- 29047254
TI  - Letter to the Editor: Breakpoints of the Mycoplasma Hominis and Ureaplasma
      Urealyticum.

PMID- 29047255
TI  - The Author Reply: Breakpoints of the Mycoplasma Hominis and Ureaplasma
      Urealyticum.

PMID- 29047256
TI  - Analysis of Genes with Alternatively Spliced Transcripts in the Leaf, Root,
      Panicle and Seed of Rice Using a Long Oligomer Microarray and RNA-Seq.
AB  - Pre-mRNA splicing further increases protein diversity acquired through evolution.
      The underlying driving forces for this phenomenon are unknown, especially in
      terms of gene expression. A rice alternatively spliced transcript detection
      microarray (ASDM) and RNA sequencing (RNA-Seq) were applied to differentiate the
      transcriptome of 4 representative organs of Oryza sativa L. cv. Ilmi: leaves,
      roots, 1-cm-stage panicles and young seeds at 21 days after pollination.
      Comparison of data obtained by microarray and RNA-Seq showed a bell-shaped
      distribution and a co-lineation for highly expressed genes. Transcripts were
      classified according to the degree of organ enrichment using a coefficient value
      (CV, the ratio of the standard deviation to the mean values): highly variable
      (CVI), variable (CVII), and constitutive (CVIII) groups. A higher index of the
      portion of loci with alternatively spliced transcripts in a group (IAST) value
      was observed for the constitutive group. Genes of the highly variable group
      showed the characteristics of the examined organs, and alternatively spliced
      transcripts tended to exhibit the same organ specificity or less organ
      preferences, with avoidance of 'organ distinctness'. In addition, within a locus,
      a tendency of higher expression was found for transcripts with a longer coding
      sequence (CDS), and a spliced intron was the most commonly found type of
      alternative splicing for an extended CDS. Thus, pre-mRNA splicing might have
      evolved to retain maximum functionality in terms of organ preference and
      multiplicity.

PMID- 29047257
TI  - Rice 7-Hydroxymethyl Chlorophyll a Reductase Is Involved in the Promotion of
      Chlorophyll Degradation and Modulates Cell Death Signaling.
AB  - The loss of green coloration via chlorophyll (Chl) degradation typically occurs
      during leaf senescence. To date, many Chl catabolic enzymes have been identified
      and shown to interact with light harvesting complex II to form a Chl degradation
      complex in senescing chloroplasts; this complex might metabolically channel
      phototoxic Chl catabolic intermediates to prevent oxidative damage to cells. The
      Chl catabolic enzyme 7-hydroxymethyl Chl a reductase (HCAR) converts 7
      hydroxymethyl Chl a (7-HMC a) to Chl a. The rice (Oryza sativa) genome contains a
      single HCAR homolog (OsHCAR), but its exact role remains unknown. Here, we show
      that an oshcar knockout mutant exhibits persistent green leaves during both dark
      induced and natural senescence, and accumulates 7-HMC a and pheophorbide a (Pheo
      a) in green leaf blades. Interestingly, both rice and Arabidopsis hcar mutants
      exhibit severe cell death at the vegetative stage; this cell death largely occurs
      in a light intensity-dependent manner. In addition, 7-HMC a treatment led to the
      generation of singlet oxygen (1O2) in Arabidopsis and rice protoplasts in the
      light. Under herbicide-induced oxidative stress conditions, leaf necrosis was
      more severe in hcar plants than in wild type, and HCAR-overexpressing plants were
      more tolerant to reactive oxygen species than wild type. Therefore, in addition
      to functioning in the conversion of 7-HMC a to Chl a in senescent leaves, HCAR
      may play a critical role in protecting plants from high light-induced damage by
      preventing the accumulation of 7-HMC a and Pheo a in developing and mature leaves
      at the vegetative stage.

PMID- 29047258
TI  - Identification and Expression Analyses of Equine Endogenous Retroviruses in
      Horses.
AB  - Endogenous retroviruses (ERVs) have been integrated into vertebrate genomes and
      have momentously affected host organisms. Horses (Equus caballus) have been
      domesticated and selected for elite racing ability over centuries. ERVs played an
      important role in the evolutionary diversification of the horse genome. In the
      present study, we identified six equine ERV families (EqERVs-E1, I1, M2, P1, S1,
      and Y4), their full-length viral open reading frames (ORFs), and elucidated their
      phylogenetic relationships. The divergence time of EqERV families assuming an
      evolutionary rate of 0.2%/Myr indicated that EqERV-S3 (75.4 million years ago;
      mya) on chromosome 10 is an old EqERV family and EqERV-P5 (1.2 Mya) on chromosome
      12 is a young member. During the evolutionary diversification of horses, the
      EqERV-I family diverged 1.7 Mya to 38.7 Mya. Reverse transcription quantitative
      real-time PCR (RT-qPCR) amplification of EqERV pol genes showed greater
      expression in the cerebellum of the Jeju horse than the Thoroughbred horse. These
      results could contribute further dynamic studies for horse genome in relation to
      EqERV gene function.

PMID- 29047259
TI  - The Candidate Tumor Suppressor Gene SLC8A2 Inhibits Invasion, Angiogenesis and
      Growth of Glioblastoma.
AB  - Glioblastoma is the most frequent and most aggressive brain tumor in adults.
      Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but
      not present in other human normal tissues or in gliomas. Therefore, we
      hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the
      role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism.
      The glioblastoma U87MG cells stably transfected with the lentivirus plasmid
      containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed.
      In the present study, we found that the tumorigenicity of U87MG in nude mice was
      totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell
      proliferation or cell cycle, but impaired the invasion and migration of U87MG
      cells, most likely through inactivating the extracellular signal-related kinases
      (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding
      activity of nuclear factor kappa B (NF-kappaB), reducing the level of matrix
      metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its
      receptor (uPAR) system (ERK1/2-NF-kappaB-MMPs/uPA-uPAR), and altering the protein
      levels of epithelial to mesenchymal transitions (EMT)-associated proteins E
      cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of
      U87MG cells, probably through combined inhibition of endothelium-dependent and
      endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2
      serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth
      of glioblastoma.

PMID- 29047260
TI  - GSK-J4-Mediated Transcriptomic Alterations in Differentiating Embryoid Bodies.
AB  - Histone-modifying enzymes are key players in the field of cellular
      differentiation. Here, we used GSK-J4 to profile important target genes that are
      responsible for neural differentiation. Embryoid bodies were treated with
      retinoic acid (10 MUM) to induce neural differentiation in the presence or
      absence of GSK-J4. To profile GSKJ4-target genes, we performed RNA sequencing for
      both normal and demethylase-inhibited cells. A total of 47 and 58 genes were up-
      and down-regulated, respectively, after GSK-J4 exposure at a log2-fold-change cut
      off value of 1.2 (p-value < 0.05). Functional annotations of all of the
      differentially expressed genes revealed that a significant number of genes were
      associated with the suppression of cellular proliferation, cell cycle progression
      and induction of cell death. We also identified an enrichment of potent motifs in
      selected genes that were differentially expressed. Additionally, we listed
      upstream transcriptional regulators of all of the differentially expressed genes.
      Our data indicate that GSK-J4 affects cellular biology by inhibiting cellular
      proliferation through cell cycle suppression and induction of cell death. These
      findings will expand the current understanding of the biology of histone
      modifying enzymes, thereby promoting further investigations to elucidate the
      underlying mechanisms.

PMID- 29047261
TI  - Deciphering the Genes for Taste Receptors for Fructose in Drosophila.
AB  - Taste sensitivity to sugars plays an essential role in the initiation of feeding
      behavior. In Drosophila melanogaster, recent studies have identified several
      gustatory receptor (Gr) genes required for sensing sweet compounds. However, it
      is as yet undetermined how these GRs function as taste receptors tuned to a wide
      range of sugars. Among sugars, fructose has been suggested to be detected by a
      distinct receptor from other sugars. While GR43A has been reported to sense
      fructose in the brain, it is not expressed in labellar gustatory receptor neurons
      that show taste response to fructose. In contrast, the Gr64a-Gr64f gene cluster
      was recently shown to be associated with fructose sensitivity. Here we sought to
      decipher the genes required for fructose response among Gr64a-Gr64f genes.
      Unexpectedly, the qPCR analyses for these genes show that labellar expression
      levels of Gr64d and Gr64e are higher in fructose low-sensitivity flies than in
      high-sensitivity flies. Moreover, gustatory nerve responses to fructose in
      labellar sensilla are higher in Gr64d and Gr64f mutant lines than in mutant flies
      of the other Gr64a-Gr64f genes. These data suggest the possibility that deletion
      of GR64D or GR64F may indirectly induce enhanced fructose sensitivity in the
      labellum. Finally, we conclude that response to fructose cannot be explained by a
      single one of the Gr64a-Gr64f genes.

PMID- 29047262
TI  - Current Understanding of RANK Signaling in Osteoclast Differentiation and
      Maturation.
AB  - Osteoclasts are bone-resorbing cells that are derived from hematopoietic
      precursor cells and require macrophage-colony stimulating factor and receptor
      activator of nuclear factor-kappaB ligand (RANKL) for their survival,
      proliferation, differentiation, and activation. The binding of RANKL to its
      receptor RANK triggers osteoclast precursors to differentiate into osteoclasts.
      This process depends on RANKL-RANK signaling, which is temporally regulated by
      various adaptor proteins and kinases. Here we summarize the current understanding
      of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the
      early stage, RANK signaling is mediated by recruiting adaptor molecules such as
      tumor necrosis factor receptor-associated factor 6 (TRAF6), which leads to the
      activation of mitogen-activated protein kinases (MAPKs), and the transcription
      factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1).
      Activated NF-kappaB induces the nuclear factor of activated T-cells cytoplasmic 1
      (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate
      stage of signaling, the co-stimulatory signal induces Ca2+ oscillation via
      activated phospholipase Cgamma2 (PLCgamma2) together with c-Fos/AP-1, wherein
      Ca2+ signaling facilitates the robust production of NFATc1. In the late stage of
      osteoclastogenesis, NFATc1 translocates into the nucleus where it induces
      numerous osteoclast-specific target genes that are responsible for cell fusion
      and function.

PMID- 29047263
TI  - Cross-talk between Phosphate Starvation and Other Environmental Stress Signaling
      Pathways in Plants.
AB  - The maintenance of inorganic phosphate (Pi) homeostasis is essential for plant
      growth and yield. Plants have evolved strategies to cope with Pi starvation at
      the transcriptional, post-transcriptional, and post-translational levels, which
      maximizes its availability. Many transcription factors, miRNAs, and transporters
      participate in the Pi starvation signaling pathway where their activities are
      modulated by sugar and phytohormone signaling. Environmental stresses
      significantly affect the uptake and utilization of nutrients by plants, but their
      effects on the Pi starvation response remain unclear. Recently, we reported that
      Pi starvation signaling is affected by abiotic stresses such as salt, abscisic
      acid, and drought. In this review, we identified transcription factors, such as
      MYB, WRKY, and zinc finger transcription factors with functions in Pi starvation
      and other environmental stress signaling. In silico analysis of the promoter
      regions of Pi starvation-responsive genes, including phosphate transporters,
      microRNAs, and phosphate starvation-induced genes, suggest that their expression
      may be regulated by other environmental stresses, such as hormones, drought,
      cold, heat, and pathogens as well as by Pi starvation. Thus, we suggest the
      possibility of cross-talk between Pi starvation signaling and other environmental
      stress signaling pathways.

PMID- 29047265
TI  - Editorial: Telemedicine/e-health as mediated communication.

PMID- 29047264
TI  - The Inactivation of ERK1/2, p38 and NF-kB Is Involved in the Down-Regulation of
      Osteoclastogenesis and Function by A2B Adenosine Receptor Stimulation.
AB  - A2B adenosine receptor (A2BAR) is known to be the regulator of bone homeostasis,
      but its regulatory mechanisms in osteoclast formation are less well-defined.
      Here, we demonstrate the effect of A2BAR stimulation on osteoclast
      differentiation and activity by RANKL. A2BAR was expressed in bone marrow-derived
      monocyte/macrophage (BMM) and RANKL increased A2BAR expression during
      osteoclastogenesis. A2BAR stimulation with its specific agonist BAY 60-6583 was
      sufficient to inhibit the activation of ERK1/2, p38 MAP kinases and NF-kappaB by
      RANKL as well as it abrogated cell-cell fusion in the late stage of osteoclast
      differentiation. Stimulation of A2BAR suppressed the expression of osteoclast
      marker genes, such as c-Fos, TRAP, Cathepsin-K and NFATc1, induced by RANKL, and
      transcriptional activity of NFATc1 was also inhibited by stimulation of A2BAR.
      A2BAR stimulation caused a notable reduction in the expression of Atp6v0d2 and DC
      STAMP related to cell-cell fusion of osteoclasts. Especially, a decrease in bone
      resorption activity through suppression of actin ring formation by A2BAR
      stimulation was observed. Taken together, these results suggest that A2BAR
      stimulation inhibits the activation of ERK1/2, p38 and NF-kappaB by RANKL, which
      suppresses the induction of osteoclast marker genes, thus contributing to the
      decrease in osteoclast cell-cell fusion and bone resorption activity.

PMID- 29047266
TI  - Instantaneous Wave-free Ratio versus Fractional Flow Reserve.

PMID- 29047267
TI  - Instantaneous Wave-free Ratio versus Fractional Flow Reserve.

PMID- 29047268
TI  - Liquid Chromatography-Mass Spectrometry Analysis Reveals Hydrolyzed Gluten in
      Beers Crafted To Remove Gluten.
AB  - During brewing, gluten proteins may be solubilized, modified, complexed,
      hydrolyzed, and/or precipitate. Gluten fragments that persist in conventional
      beers render them unsuitable for people with celiac disease (CD) or gluten
      intolerance. Barley-based beers crafted to remove gluten using proprietary
      precipitation and/or application of enzymes, e.g. prolyl endopeptidases (PEP)
      that degrade the proline-rich gluten molecules, are available commercially.
      Gluten measurement in fermented products remains controversial. The industry
      standard, a competitive ELISA, may indicate gluten values <20 mg/kg, which is
      deemed safe for people with CD. However, in this study, liquid chromatography
      mass spectrometry analyses revealed gluten peptides derived from hydrolyzed
      fragments, many >30 kDa in size. Barley gluten (hordeins) were detected in all
      beers analyzed with peptides representing all hordein classes detected in
      conventional beers but also, alarmingly, in many gluten-reduced beers. It is
      evident that PEP digestion was incomplete in several commercial beers, and
      peptides comprising missed cleavages were identified, warranting further
      optimization of PEP application in an industrial setting.

PMID- 29047269
TI  - High-Speed, Self-Biased Broadband Photodetector-Based on a Solution-Processed Ag
      Nanowire/Si Schottky Junction.
AB  - In this work, we demonstrate the effectiveness of Ag nanowires (AgNWs) to design
      a high-speed broadband photodetector. A simple AgNW solution was spin-coated on a
      Si substrate to form a Schottky junction. The junction properties were
      investigated using current-voltage characteristics and Mott-Schottky analysis.
      The present device had a remarkably fast response speed, e.g., rising time taur =
      784 ns and fall time tauf = 92 MUs, with good reproducibility over a wide range
      of switching frequencies (50 Hz-50 kHz). Such a high performance was attributed
      to the strong electric field created at the AgNW/Si interface without an external
      electric field, enabling the efficient separation of photogenerated electron-hole
      pairs. The present study will open a new avenue to design future optoelectronic
      devices and energy devices including solar cells.

PMID- 29047270
TI  - Three-Component Catalytic Carboxygenation of Activated Alkenes Enabled by
      Bimetallic Rh(III)/Cu(II) Catalysis.
AB  - A novel cascade Cp*Rh(III)-catalyzed C-H alkylation/Cu(II)-promoted alpha
      oxygenation which enabled a three-component carboxygenation of activated alkene
      is reported. Mild reaction conditions, broad substrate scope, and good functional
      group tolerance were observed. The synthetic utility of the protocol was
      showcased by the facile transformations of the product to a variety of
      structurally diverse molecules. Preliminary mechanistic studies were conducted.

PMID- 29047271
TI  - Synthesis of Benzoaryl-5-yl(2-hydroxyphenyl)methanones via Photoinduced
      Rearrangement of (E)-3-Arylvinyl-4H-chromen-4-ones.
AB  - A concise and efficient photoinduced rearrangement of (E)-3-arylvinyl-4H-chromen
      4-ones for the synthesis of benzoaryl-5-yl(2-hydroxyphenyl)methanones is
      described. Benzoaryl-5-yl-(2-hydroxyphenyl)methanones were obtained in 77-95%
      yields via the irradiation of (E)-3-arylvinyl-chromones in the 95% EtOH with a
      high-pressure mercury lamp at room temperature under Ar atmosphere. The reported
      method provides a novel procedure for the synthesis of alpha,alpha'-diaryl ketone
      derivatives without addition of any transition metals and oxidants or other
      additives. A plausible mechanism was proposed, and the rearrangement product was
      characterized by NMR, HRMS, and X-ray.

PMID- 29047272
TI  - Three-Dimensional Lupinus-like TiO2 Nanorod@Sn3O4 Nanosheet Hierarchical
      Heterostructured Arrays as Photoanode for Enhanced Photoelectrochemical
      Performance.
AB  - A novel photoelectrode of three-dimensional (3D) lupinus-like TiO2 nanorod@Sn3O4
      nanosheet hierarchical heterostructured arrays (TiO2@Sn3O4 HHAs) on a transparent
      F-doped SnO2 glass substrate was designed and fabricated by a two-step
      solvothermal growth process. Photoelectrochemical (PEC) measurements showed that
      the 3D lupinus-like TiO2@Sn3O4 HHAs photoelectrode displayed enhanced
      photocurrent density (3-fold increase with respect to that of pure TiO2),
      improved conversion efficiency, more negative onset potential (from -0.13 to 
      0.33 V vs normal hydrogen electrode), and higher light on/off cycle stability.
      The improved PEC properties may be ascribable to the enhancement of light
      harvesting and large contact area with the electrolyte by increased surface area
      as well as improvement of charge transfer and collection through the synergistic
      effects between band structures and morphology.

PMID- 29047273
TI  - Thiophene-Thiazole-Based Semiconducting Copolymers for High-Performance Polymer
      Field-Effect Transistors.
AB  - We report a newly synthesized donor (D)-acceptor (A)type semiconducting
      copolymer, consisting of thiophene as an electron-donating unit and thiazole as
      an electron-accepting unit (PQTBTz-TT-C8) for the active layer of the organic
      field-effect transistors (OFETs). Specifically, this study investigates the
      structure and electrical property relationships of PQTBTz-TT-C8 with
      comprehensive analyses on the charge-transporting properties corresponding to the
      spin rate of the spin coater during the formation of the PQTBTz-TT-C8 film. The
      crystallinity of PQTBTz-TT-C8 films is examined with grazing incidence X-ray
      diffraction. Temperature-dependent transfer measurements of the OFETs are
      conducted to extract the density of states (DOS) and characterize the charge
      transport properties. Comparative analyses on charge transports within the
      framework of the physical model, based on polaron hopping and Gaussian DOS,
      reveal that the prefactors of both physical charge-transport models are
      independent of the spin-coating condition for the films. For staggered structural
      transistors, however, the thickness of the PQTBTz-TT-C8 films, which strongly
      affect the series resistance along the charge-transfer path in a vertical
      direction, is changed in accordance with the spin-coating rate. In other words,
      the spin-coating rate of the PQTBTz-TT-C8 films influences the thickness of the
      polymer films, yet any significant changes in the crystallinity of the film or
      electronic coupling between the neighboring molecules upon the spin-coating
      condition were barely noticeable. Because the PQTBTz-TT-C8 backbone chains inside
      the thin film are stacked up with the edge-on, the series resistances are changed
      according to the thickness of the film and thus the performance of the device
      varies depending on the thickness.

PMID- 29047274
TI  - Asymmetric alpha-Allylation of alpha-Substituted beta-Ketoesters with Allyl
      Alcohols.
AB  - Enantioselective alpha-allylation of alpha-substituted beta-ketoesters with
      simple allyl alcohols was successfully performed by synergistic catalysis with
      the catalyst combination of a chiral primary amino acid and an achiral palladium
      complex without additional promotors like acids or bases. The allylation reaction
      and generation of a chiral quaternary carbon stereocenter proceeded smoothly to
      produce alpha,alpha-disubstituted beta-ketoesters in high yields (91-99%) with
      high enantioselectivities (90-99% ee).

PMID- 29047275
TI  - Excipient-Free Pulmonary Delivery and Macrophage Targeting of Clofazimine via Air
      Jet Micronization.
AB  - Clofazimine (CFZ) is highly active against mycobacterium, including resistant
      Mycobacterium tuberculosis, but its therapeutic efficacy via the oral route is
      limited by severe adverse effects, poor aqueous solubility, and slow onset of
      action. Pulmonary delivery of CFZ is an attractive alternative to target
      mycobacterium-harboring alveolar macrophages. This study explores the use of air
      jet milling to develop a respirable, cost-effective CFZ formulation. Jet milled
      CFZ was readily dispersed from an off-the-shelf dry powder inhaler without the
      need for additional excipients or carrier particles. Additionally, milled CFZ was
      internalized by J774.A1 alveolar macrophages within 8 h, with evidence of
      intracellular biotransformation of the CFZ crystals and macrophage sequestration
      by 24 h. Less macrophage toxicity was noted in comparison to solubilized drug.
      Compared to macrophage uptake rate, dissolution of milled CFZ was limited,
      thereby potentially reducing systemic absorption and subsequent side effects.
      These results suggest that jet milling is an effective manufacturing method in
      the development of a CFZ formulation for pulmonary delivery and alveolar
      macrophage targeting.

PMID- 29047276
TI  - pi-Extended Isoindigo-Based Derivative: A Promising Electron-Deficient Building
      Block for Polymer Semiconductors.
AB  - The exploration of novel electron-deficient building blocks is a key task for
      developing high-performance polymer semiconductors in organic thin-film
      transistors. In view of the situation of the lack of strong electron-deficient
      building blocks, we designed two novel pi-extended isoindigo-based electron
      deficient building blocks, IVI and F4IVI. Owing to the strong electron-deficient
      nature and the extended pi-conjugated system of the two acceptor units, their
      copolymers, PIVI2T and PF4IVI2T, containing 2,2'-bithiophene donor units, are
      endowed with deep-lying highest occupied molecular orbital (HOMO)/lowest
      unoccupied molecular orbital (LUMO) energy levels and strong intermolecular
      interactions. In comparison to PIVI2T, the fluorinated PF4IVI2T exhibits stronger
      intra- and intermolecular interactions, lower HOMO/LUMO energy levels up to 
      5.74/-4.17 eV, and more ordered molecular packing with a smaller pi-pi stacking
      distance of up to 3.53 A, resulting in an excellent ambipolar transporting
      behavior and a promising application in logic circuits for PF4IVI2T in ambient
      with hole and electron mobilities of up to 1.03 and 1.82 cm2 V-1 s-1,
      respectively. The results reveal that F4IVI is a promising and strong electron
      deficient building unit to construct high-performance semiconducting polymers,
      which provides an insight into the structure-property relationships for the
      exploration and molecular engineering of excellent electron-deficient building
      blocks in the field of organic electronics.

PMID- 29047278
TI  - Copper-Catalyzed Arylsulfonylation and Cyclizative Carbonation of N
      (Arylsulfonyl)acrylamides Involving Desulfonative Arrangement toward Sulfonated
      Oxindoles.
AB  - Sulfonated oxindoles are accessed by a Cu(OAc)2-catalyzed three-component
      reaction of N-(arylsulfonyl)acrylamides, DABSO, and aryldiazonium
      tetrafluoroborates. This transformation is triggered by the formation of
      arylsulfonyl radicals in situ from the reaction of aryldiazonium
      tetrafluoroborates and DABSO. Afterward, the sequential radical addition, radical
      cyclization, and desulfonylative 1,4-aryl migration take place to provide the
      final product by the formation of four new bonds in one pot. This procedure shows
      good functional group tolerance.

PMID- 29047277
TI  - Regioselective Synthesis of 5-Aminooxazoles via Cp*Co(III)-Catalyzed Formal [3 +
      2] Cycloaddition of N-(Pivaloyloxy)amides with Ynamides.
AB  - A simple and efficient protocol for the regioselective synthesis of 5
      aminooxazoles is disclosed. The reaction, catalyzed by a cheap Cp*Co(III)
      catalyst, starts from easily accessible N-(pivaloyloxy)amides and ynamides. Mild
      reaction conditions, a broad substrate scope, good functional group tolerance,
      and good to excellent yields were observed.

PMID- 29047279
TI  - High-Performance Photoelectronic Sensor Using Mesostructured ZnO Nanowires.
AB  - Semiconductor photoelectrodes that simultaneously possess rapid charge transport
      and high surface area are highly desirable for efficient charge generation and
      collection in photoelectrochemical devices. Herein, we report mesostructured ZnO
      nanowires (NWs) that not only demonstrate a surface area as high as 50.7 m2/g,
      comparable to that of conventional nanoparticles (NPs), but also exhibit a 100
      times faster electron transport rate than that in NP films. Moreover, using the
      comparison between NWs and NPs as an exploratory platform, we show that the
      synergistic effect between rapid charge transport and high surface area leads to
      a high performance photoelectronic formaldehyde sensor that exhibits a detection
      limit of as low as 5 ppb and a response of 1223% (at 10 ppm), which are,
      respectively, over 100 times lower and 20 times higher than those of conventional
      NPs-based device. Our work establishes a foundational pathway toward a better
      photoelectronic system by materials design.

PMID- 29047280
TI  - Adhesion of Phospholipid Bilayers to Hydroxylated Silica: Existence of Nanometer
      Thick Water Interlayers.
AB  - Lipid bilayers attached to solid surfaces play an important role in bioinspired
      materials and devices and serve as model systems for studies of interactions of
      cell membranes with particles and biomolecules. Despite active experimental and
      theoretical studies, the interactions of lipid membranes with solid substrates
      are still poorly understood. In this work, we explore, using atomistic molecular
      dynamics simulations, the equilibrium and stability of a phospholipid 1,2
      dimyristoyl-sn-glycero-3-phosphocholine membrane supported on hydroxylated
      amorphous silica. We reveal two distinct types of thermodynamically stable
      states, characterized by different widths of the water layer between the membrane
      and the substrate. In alpha-states, the membrane is closely attached with the
      lipid head groups interacting directly with surface hydroxyls; however, because
      of the molecular level roughness of the amorphous silica surface, there exists an
      inhomogeneous water layer trapped between the substrate and the membrane. In beta
      states, the membrane is separated from the silica surface by a water film of ~2.5
      nm in thickness. The thermodynamic equilibrium is quantified in terms of the
      disjoining pressure isotherm as a function of membrane-substrate separation,
      which has a double sigmoidal shape with two minima and one maximum, which
      correspond to the limits of stability of alpha- and beta-states. The
      thermodynamic properties and bilayer structure are compared with experimental
      findings and simulation results for relevant systems.

PMID- 29047281
TI  - Development of Wheat Bran Oil Concentrates Rich in Bioactives with Antioxidant
      and Hypolipidemic Properties.
AB  - Wheat bran, an abundant byproduct of the milling industry, comprises fat-soluble
      bioactives and fibers. In the present study, two concentrates were prepared from
      wheat bran oil (WBO) using silicic acid coupled with acetone (WBA) and hexane
      (WBH). WBA extract had enhanced color and viscosity and was enriched with fat
      soluble bioactives (sterols, oryzanol-like compounds, tocopherols, and
      carotenoids) as evidenced from NMR and other techniques. In in vitro studies, WBA
      exhibited significant free radical scavenging activity, limited DNA and LDL
      oxidation, and inhibiting HMG-CoA reductase and lipase activity better than WBH
      and WBO. Further, an in vivo study with WBA 2 or 3.5% containing high fat diet
      ameliorated malonaldehyde (MDA) level, lipid profile, and antioxidant enzyme
      (SOD, catalase, GPx, and GR) activities in liver. A possible reason for this
      effect is downregulation of HMG-CoA reductase expression with WBA. Thus, WBA has
      significant potential as an ingredient in health food formulations.

PMID- 29047283
TI  - [Articles of the Hungarian Medical Journal from January, 2005].

PMID- 29047284
TI  - [Articles of the Hungarian Medical Journal from September, 2005].

PMID- 29047282
TI  - A New Cell Separation Method Based on Antibody-Immobilized Nanoneedle Arrays for
      the Detection of Intracellular Markers.
AB  - Focusing on intracellular targets, we propose a new cell separation technique
      based on a nanoneedle array (NNA) device, which allows simultaneous insertion of
      multiple needles into multiple cells. The device is designed to target and lift
      ("fish") individual cells from a mixed population of cells on a substrate using
      an antibody-functionalized NNA. The mechanics underlying this approach were
      validated by force analysis using an atomic force microscope. Accurate high
      throughput separation was achieved using one-to-one contacts between the
      nanoneedles and the cells by preparing a single-cell array in which the positions
      of the cells were aligned with 10,000 nanoneedles in the NNA. Cell-type-specific
      separation was realized by controlling the adhesion force so that the cells could
      be detached in cell-type-independent manner. Separation of nestin-expressing
      neural stem cells (NSCs) derived from human induced pluripotent stem cells
      (hiPSCs) was demonstrated using the proposed technology, and successful
      differentiation to neuronal cells was confirmed.

PMID- 29047285
TI  - [Articles of the Hungarian Medical Journal from April, 2005].

PMID- 29047286
TI  - [Articles of the Hungarian Medical Journal from August, 2005].

PMID- 29047287
TI  - [Articles of the Hungarian Medical Journal from March, 2005].

PMID- 29047289
TI  - [Articles of the Hungarian Medical Journal from November, 2005].

PMID- 29047288
TI  - Upregulating Positive Affectivity in the Transdiagnostic Treatment of Emotional
      Disorders: A Randomized Pilot Study.
AB  - Transdiagnostic cognitive-behavioral therapy for emotional disorders (ED) has
      proven to be effective. However, current transdiagnostic treatment protocols
      address only the regulation of negative affectivity, and they do not include
      treatment components to more directly target the regulation of positive
      affectivity. In this study, we propose to evaluate the preliminary efficacy and
      acceptability of a transdiagnostic treatment protocol for ED that includes, as an
      innovative feature, a specific treatment component to directly upregulate
      positive affectivity based on positive psychology interventions. A total of 24
      participants were randomized to either a transdiagnostic treatment protocol ( n =
      12) or a transdiagnostic treatment protocol with an additional component designed
      to regulate positive affectivity ( n = 12). Participants completed measures of
      anxiety, depression, positive and negative affectivity, and quality of life, as
      well as treatment acceptability at pre- and posttreatment and at the 3-month
      follow-up. Both interventions led to improvements in all measures at
      posttreatment, and these outcomes were maintained at the 3-month follow-up, with
      large effect sizes for all measures. The effect sizes for positive affect were
      larger in the condition that included the component to upregulate positive
      affectivity. Attrition rate was low, and both treatment protocols were well
      accepted by participants. The results obtained in this study indicate the
      feasibility of testing the treatment protocol in a larger, randomized, controlled
      trial, and they suggest the potential of including treatment components for
      directly upregulating positive affectivity in future research on transdiagnostic
      treatment protocols for ED.

PMID- 29047290
TI  - Understanding Factors Related to Prolonged Trial of Detained Defendants in the
      Philippines.
AB  - Utilizing a combination of jail official data and qualitative data gathered
      through Focus Group Discussions and interviews with inmates, court actors, and
      jail officers, this article investigates the factors related to prolonged trial
      of detained defendants in the Philippines. Sensitizing concepts derived from
      Western literature are utilized to understand individual, court, and jail-level
      variations to prolonged detention. Results from official jail data show the
      magnitude and extent of the problem. The narrative data suggests the salience of
      organizational and cultural dynamics that lead to the delay of cases for detained
      defendants. Specifically, courts that are loosely coupled and subscribe to
      workgroup culture that condones leniency are more likely to be delayed.
      Implications to theory and policy are discussed.

PMID- 29047291
TI  - Recurrent moderate hypoglycemia exacerbates oxidative damage and neuronal death
      leading to cognitive dysfunction after the hypoglycemic coma.
AB  - Moderate recurrent hypoglycemia (RH) is frequent in Type 1 diabetes mellitus
      (TIDM) patients who are under intensive insulin therapy increasing the risk for
      severe hypoglycemia (SH). The consequences of RH are not well understood and its
      repercussions on neuronal damage and cognitive function after a subsequent
      episode of SH have been poorly investigated. In the current study, we have
      addressed this question and observed that previous RH during seven consecutive
      days exacerbated oxidative damage and neuronal death induced by a subsequent
      episode of SH accompanied by a short period of coma, in the parietal cortex, the
      striatum and mainly in the hippocampus. These changes correlated with a severe
      decrease in reduced glutathione content (GSH), and a significant spatial and
      contextual memory deficit. Administration of the antioxidant, N-acetyl-L
      cysteine, (NAC) reduced neuronal death and prevented cognitive impairment. These
      results demonstrate that previous RH enhances brain vulnerability to acute
      hypoglycemia and suggests that this effect is mediated by the decline in the
      antioxidant defense and oxidative damage. The present results highlight the
      importance of an adequate control of moderate hypoglycemic episodes in TIDM.

PMID- 29047292
TI  - How we use the Internet matters for health: The relationship between various
      online health-related activities and preventive dietary behaviors.
AB  - This study identified specific types of online health-related activities that may
      promote preventive dietary behaviors. Two cycles (Cycles 1 and 3) of the Health
      Information National Trends Survey 4 were analyzed ( N = 2606 and 2284,
      respectively; Internet users only). Similar types of activities were grouped to
      create three types of online activities: information seeking, engagement in
      health information technology, and social media use. In both cycles, online
      health information seeking and the engagement in health information technology
      were positively associated with two dietary behaviors (fruit/vegetable
      consumption and using menu information on calories) but not with soda
      consumption. Individuals may be exposed to new information or become more aware
      of their current health status through information seeking or health information
      technology engagement. However, social media use for health was not related to
      any of the dietary behavior. The results suggest that "how we use the Internet"
      may make a difference in health outcomes.

PMID- 29047293
TI  - [Articles of the Hungarian Medical Journal from December, 2005].

PMID- 29047294
TI  - Deep Transverse Metatarsal Ligament Transection in Morton's Neuroma Excision: A
      Cadaveric Study Examining Effects on Metatarsal Alignment.
AB  - BACKGROUND: In the dorsal incisional approach for Morton's neuroma, it is
      required to transect the deep transverse metatarsal ligament (DTML) that lies in
      the interspace between the third and fourth metatarsal heads. The purpose of this
      study was to evaluate the relationship between transection of the DTML in the
      third intermetatarsal space and the metatarsal alignment. METHODS: Nine human
      cadaveric lower extremity limbs were used for this study. Each limb was mounted
      to the MTS 858 Mini Bionix biomechanical test system and loaded to 120% of the
      donor's documented body weight at a rate of 15 lbf/s, in order to simulate peak
      weightbearing ground reactive forces on the forefoot. Preoperative and immediate
      postoperative radiographs were obtained. Cyclic loading was then performed to
      simulate 1 month of full weightbearing. Radiographs were repeated and metatarsal
      alignment was analyzed. RESULTS: A statistically significant difference was noted
      with intermetatarsal angle (IMA) 1-2 and IMA 1-4. The IMA 1-2 after 1 month
      cycling time showed statistical significant difference from those found
      immediately postoperatively (P < .05). Average increase in IMA 1-2 from
      preoperative to 1 month cycling time was 2.18 degrees . The power of the analyses
      for IMA 1-2 was 0.992. Regarding the IMA 1-4, data recorded at 1 week and 1 month
      cycling times showed a statistically significant difference compared to the
      preoperative IMA 1-4 (P < .05). Average increase in IM 1-4 angles from
      preoperative to 1 month cycling time was an increase of 1.79 degrees . The power
      of the analyses for IM 1-4 angles was 0.953. CONCLUSION: Technically, 2.18
      degrees  increase in IMA 1-2 or 1.79 degrees  increase in IM 1-4 would be
      considered an abnormal widening of the forefoot, but clinically, these values
      could not be detected; nor should they deter a surgeon or patient from undergoing
      a Morton's neurectomy via a dorsal incisional approach. LEVELS OF EVIDENCE: Level
      V: Cadaveric study.

PMID- 29047295
TI  - Enhanced Irrigant Delivery to the Ethmoid Sinuses Directly Following Ethmoid
      Punch Sinusotomy.
AB  - OBJECTIVES: Ethmoid punch sinusotomy (EPS) is a feasible treatment for ethmoid
      sinusitis in a subset of chronic rhinosinusitis (CRS) patients per a recent
      report. This adjunctive work investigates the technical characteristics of EPS
      and determines if EPS measurably alters the topical delivery of irrigant into the
      ethmoid sinuses in a cadaveric model. METHODS: The sinonasal cavities of 10 human
      cadaver heads were irrigated with a solution containing methylene blue and radio
      opaque contrast prior to and following EPS. Procedural characteristics and
      irrigant distribution were assessed by endoscopy and computed tomography.
      RESULTS: Forty EPS procedures were performed through the ethmoid bulla and basal
      lamella. Compared to controls, EPS enhanced dye distribution into the anterior
      (90% vs 35%, P < .004) and posterior (90% vs 35%, P < .002) ethmoid sinuses,
      representing a 157% increase for each of these sites. Contrast was detected in a
      higher proportion of anterior (65% vs 5%, P < .001) and posterior (60% vs 0%, P <
      .001) ethmoid sinuses. Endoscopically guided catheter instillation of contrast
      through the EPS sites achieved radiotracer distribution throughout the ethmoid
      complex. CONCLUSIONS: Ethmoid punch sinusotomy sites can be reliably created via
      micro-minimally invasive procedures. Ethmoid punch sinusotomy improves irrigant
      delivery to the ethmoid sinuses, providing mechanistic understanding for the
      clinical outcomes observed in CRS patients.

PMID- 29047297
TI  - Inhibition of the solid state transformation of carbamazepine in aqueous
      solution: impact of polymeric properties.
AB  - The effects of polymers on the anhydrate-to-hydrate transformation of
      carbamazepine (CBZ) was investigated. The three types of polymers studied were
      polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA) and substituted celluloses
      which included hydroxypropyl methylcellulose (HPMC) and methylcellulose (MC).
      Anhydrous CBZ was added to dilute aqueous polymer solutions and Raman
      spectroscopy measurements were collected to monitor the kinetics of the solution
      mediated transformation to CBZ dihydrate. Polymers exhibiting the greatest
      inhibition were able to reduce the growth phase of the solution-mediated
      transformation and change the habit of the hydrate crystal indicating polymer
      adsorption to the hydrate crystal surface as the mechanism of inhibition. The
      results of the various polymers showed that short chain substituted celluloses
      (HPMC and MC) inhibited the CBZ transformation to a much greater extent than
      longer chains. The same trend was observed for PVP and PVA, but to a lesser
      extent. These chain length effects were attributed to changes in polymer
      confirmation when adsorbed on the crystal surface. Additionally, decreasing the
      percentage of hydroxyl groups on the PVA polymer backbone reduced the ability of
      the polymer to inhibit the transformation and changing the degree of
      substitutions of methyl and hydroxypropyl groups on the cellulosic polymer
      backbone had no effect on the transformation.

PMID- 29047296
TI  - In vivo 13C MRS in the mouse brain at 14.1 Tesla and metabolic flux
      quantification under infusion of [1,6-13C2]glucose.
AB  - In vivo 13C magnetic resonance spectroscopy (MRS) enables the investigation of
      cerebral metabolic compartmentation while, e.g. infusing 13C-labeled glucose.
      Metabolic flux analysis of 13C turnover previously yielded quantitative
      information of glutamate and glutamine metabolism in humans and rats, while the
      application to in vivo mouse brain remains exceedingly challenging. In the
      present study, 13C direct detection at 14.1 T provided highly resolved in vivo
      spectra of the mouse brain while infusing [1,6-13C2]glucose for up to 5 h. 13C
      incorporation to glutamate and glutamine C4, C3, and C2 and aspartate C3 were
      detected dynamically and fitted to a two-compartment model: flux estimation of
      neuron-glial metabolism included tricarboxylic acid cycle (TCA) flux in
      astrocytes (Vg = 0.16 +/- 0.03 umol/g/min) and neurons (VTCAn = 0.56 +/- 0.03
      umol/g/min), pyruvate carboxylase activity (VPC = 0.041 +/- 0.003 umol/g/min) and
      neurotransmission rate (VNT = 0.084 +/- 0.008 umol/g/min), resulting in a
      cerebral metabolic rate of glucose (CMRglc) of 0.38 +/- 0.02 umol/g/min, in
      excellent agreement with that determined with concomitant 18F-fluorodeoxyglucose
      positron emission tomography (18FDG PET).We conclude that modeling of neuron
      glial metabolism in vivo is accessible in the mouse brain from 13C direct
      detection with an unprecedented spatial resolution under [1,6-13C2]glucose
      infusion.

PMID- 29047299
TI  - [Articles of the Hungarian Medical Journal from February, 2006].

PMID- 29047298
TI  - Anti obese potential of Cucurbita maxima seeds oil: effect on lipid profile and
      histoarchitecture in high fat diet induced obese rats.
AB  - In this study, we made an attempt to evaluate the potential of Cucurbita maxima
      seeds oil (CSO) against high-fat diet (HFD)-induced obesity in rats. We
      investigated the effect of CSO (100 mg/kg body weight) supplementation over 30
      days on the changes of HFD-induced obese rats in body weight, biochemical
      parameters and lipid profile as well as investigated the effects of CSO on the
      histopathological changes. Oral administration with CSO revealed significant
      diminution in body weight gain, glucose and insulin levels, which altered the
      activity of lipid profile and restored the pathological alterations. It
      demonstrated that CSO had considerably altered these parameters when evaluated
      with HFD control rats. In conclusion, this study established that CSO prevents
      the HFD-induced obesity by altering the markers important to lipid metabolism.

PMID- 29047301
TI  - Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis.
AB  - INTRODUCTION: Pimavanserin is the first FDA-approved atypical antipsychotic drug
      indicated for the treatment of hallucinations and delusions associated with
      Parkinson's disease psychosis (PDP). Areas covered: This review focuses on the
      preclinical discovery of pimavanserin. It analyzes the pharmacological,
      behavioral and molecular mechanisms of pimavanserin and their contribution to the
      therapeutic advantages of the drug as reported in published preclinical and
      clinical studies, press releases and product labels. Expert opinion: Pimavanserin
      exhibits a unique pharmacological profile with nanomolar affinity at serotonin 5
      HT2A and 5-HT2C receptors. Functionally, it acts as a potent inverse agonist at 5
      HT2A receptors, with selectivity over 5-HT2C receptors and no appreciable
      activity at other neurotransmitter receptors. Behavioral studies found that
      pimavanserin reversed impaired behaviors in animal models predictive of
      antipsychotic activity, and with no impairment of motor functions. The drug
      exhibits long plasma half-life (57 hours), which support its once/day
      administration. A pivotal phase III clinical trial demonstrated significant
      improvement in PDP symptoms in patients receiving pimavanserin compared to
      placebo-treated patients. The drug also displayed relatively benign safety and
      tolerability profiles. Pimavanserin's mechanism of action might contribute to its
      unique psychopharmacological properties in the improved treatment of PDP, and
      perhaps psychosis in other diseases including schizophrenia and dementia-related
      psychosis.

PMID- 29047300
TI  - Cancer survivors' and partners' key concerns and quality of life.
AB  - OBJECTIVE: Understanding the concerns of cancer survivors is essential for
      effective interventions. This study was designed to identify the primary concerns
      of dyads coping with cancer, how concerns differed by role and sex, and whether
      concerns expressed during counselling were associated with survivors'
      psychosocial well-being and adjustment. DESIGN: Forty-three dyads with breast and
      prostate cancer (N = 86 participants) were enrolled in an interpersonal telephone
      counselling intervention. Audio recordings of 228 counselling sessions were
      transcribed and content analysed qualitatively to identify major themes and key
      concerns. A total of three 30-min sessions were coded for each study participant.
      Quantitative data and statistical analyses were used to predict changes in
      survivors' quality of life. MAIN OUTCOME MEASURES: Participants completed
      psychosocial well-being measures (depression, positive/negative affect, and
      relationship satisfaction), pre- and post-counselling. RESULTS: Survivors'
      concerns focused on cancer- and treatment-related issues, whereas partners'
      concerns centred on the well-being of their spouse/partner with cancer, and what
      they were doing to help their loved one cope with his/her illness. Key concerns
      for all consisted of relationship maintenance and communication issues. Further,
      discussion of these concerns was predictive of significant improvements in
      adjustment post-counselling for women with breast cancer. CONCLUSION: Discussion
      of interpersonal concerns may play a more important role in the well-being of
      women, than men, coping with cancer.

PMID- 29047302
TI  - A self-assembled clavanin A-coated amniotic membrane scaffold for the prevention
      of biofilm formation by ocular surface fungal pathogens.
AB  - Amniotic membrane (AM) is frequently used in ophthalmologic surgery for rapid
      ocular surface reconstruction. Sometimes it may create a major problem with
      associated infections after biofilm formation over the membrane. To overcome this
      problem, AM was coated with the antimicrobial peptide clavanin A. The antifungal
      activity of clavanin A in the native and self-assembled form was determined
      against the common ocular surface pathogens Candida albicans, Aspergillus
      fumigatus, Alternaria sp. and Fusarium sp. Biofilm formation over the coated
      surface was significantly reduced in comparison with the uncoated membrane. The
      coated membrane revealed effectiveness in terms of biocompatibility, cell
      attachment colonization when tested in non-cancerous 3T3 and human embryonic
      kidney (HEK)-293 cell lines. Clavanin A-coated AM also exhibited excellent
      physical, morphological and antifungal characteristics, indicating potential
      applicability for ocular surface infection control.

PMID- 29047303
TI  - [Articles of the Hungarian Medical Journal from October, 2005].

PMID- 29047304
TI  - Real-world comparison of all-cause hospitalizations, hospitalizations due to
      stroke and major bleeding, and costs for non-valvular atrial fibrillation
      patients prescribed oral anticoagulants in a US health plan.
AB  - AIMS: To compare the risk of all-cause hospitalization and hospitalizations due
      to stroke/systemic embolism (SE) and major bleeding, as well as associated
      healthcare costs for non-valvular atrial fibrillation (NVAF) patients initiating
      apixaban, dabigatran, rivaroxaban, or warfarin. MATERIALS AND METHODS: NVAF
      patients initiating apixaban, dabigatran, rivaroxaban, or warfarin were selected
      from the OptumInsight Research Database from January 1, 2013-September 30, 2015.
      Propensity score matching (PSM) was performed between apixaban and each oral
      anticoagulant. Cox models were used to estimate the risk of stroke/SE and major
      bleeding. Generalized linear and 2-part models were used to compare healthcare
      costs. RESULTS: Of the 47,634 eligible patients, 8,328 warfarin-apixaban pairs,
      3,557 dabigatran-apixaban pairs, and 8,440 rivaroxaban-apixaban pairs were
      matched. Compared to apixaban, warfarin patients were associated with a
      significantly higher risk of all-cause (hazard ratio [HR] = 1.30; 95% confidence
      interval [CI] = 1.21-1.40) as well as stroke/SE-related (HR = 1.60; 95% CI = 1.23
      2.07) and major bleeding-related (HR = 1.95; 95% CI = 1.60-2.39) hospitalization;
      rivaroxaban patients were associated with a higher risk of all-cause (HR = 1.15;
      95% CI = 1.07-1.24) and major bleeding-related hospitalization (HR = 1.71; 95% CI
      = 1.39-2.10); and dabigatran patients were associated with a higher risk of major
      bleeding hospitalization (HR = 1.46, 95% CI = 1.02-2.10). Warfarin patients had
      significantly higher major bleeding-related and total all-cause healthcare costs
      compared to apixaban patients. Rivaroxaban patients had significantly higher
      major bleeding-related costs compared to apixaban patients. No significant
      results were found for the remaining comparisons. LIMITATIONS: No causal
      relationships can be concluded, and unobserved confounders may exist in this
      retrospective database analysis. CONCLUSIONS: This study demonstrated a
      significantly higher risk of hospitalization (all-cause, stroke/SE, and major
      bleeding) associated with warfarin, a significantly higher risk of major bleeding
      hospitalization associated with dabigatran or rivaroxaban, and a significantly
      higher risk of all-cause hospitalization associated with rivaroxaban compared to
      apixaban. Lower major bleeding-related costs were observed for apixaban patients
      compared to warfarin and rivaroxaban patients.

PMID- 29047305
TI  - Influenza vaccine response: future perspectives.

PMID- 29047306
TI  - Comparison of Anti-Xa Activity in Patients Receiving Apixaban or Rivaroxaban.
AB  - BACKGROUND: There is no established method for monitoring the anticoagulant
      effects of apixaban and rivaroxaban. Linear correlation between serum levels and
      anti-Xa activity has been shown, with r2 ranging from 0.88 to 0.99. However,
      there are minimal data in patients receiving apixaban 5 mg twice daily or
      rivaroxaban 20 mg once daily. OBJECTIVE: To evaluate the anti-Xa activity and
      serum levels at those doses and compare the trough anti-Xa activity. METHODS:
      This was a single-center prospective study,approved by the institutional review
      board. Patients on an inappropriate dose or receiving an interacting drug were
      excluded. Blood samples were drawn 0.5 to 3 hours before a dose for both agents,
      2 to 3 hours after an apixaban dose, and 12 to 16 hours after a rivaroxaban dose.
      Anti-Xa activity and serum levels were determined, and correlation was done via
      regression analysis. Trough anti-Xa activity was compared using a t-test.
      RESULTS: The study enrolled 88 patients receiving each drug. The r2 values were
      0.79 and 0.87 for apixaban and rivaroxaban, respectively. The mean trough anti-Xa
      activity was 1.79 +/- 0.96 IU/mL for apixaban and 1.25 +/- 0.88 IU for
      rivaroxaban ( P < 0.01). The trough sample was drawn a mean of 1.3 and 1.8 hours
      prior to the next dose for apixaban and rivaroxaban, respectively ( P < 0.01).
      CONCLUSIONS: Good correlation was shown between anti-Xa activity and serum
      levels. The clinical utility of monitoring anti-Xa activity and the significance
      of the difference in trough anti-Xa activity for these agents remains to be
      established.

PMID- 29047307
TI  - Roland Hauspie (April 8, 1948-April 25, 2017).

PMID- 29047308
TI  - Characterization of organophosphate pesticides in urine and home environment dust
      in an agricultural community.
AB  - CONTEXT: Organophosphorus insecticides (OPs) have been used to control
      agricultural pests found in Washington state. Farmworkers (FW) have higher
      exposure to OP pesticides than non-farmworkers (NFW), and FW children may in turn
      have higher exposure than NFW children. OBJECTIVE: To examine the association
      between the concentration in house dust of five OPs used commonly in pome fruit
      orchards and the concentration in urine of dialkylphosphate metabolites (DAP), in
      a cohort of Hispanic FW and NFW and their children. METHODS: Parents and children
      participated in three data collection periods over the course of one year. Urine
      samples were evaluated for the DAPs characteristic of OP exposure, and dust from
      homes and vehicles was evaluated for intact OP residues. RESULTS: Geometric mean
      (GM) concentrations of OPs in house and vehicle dust were higher in FW households
      than NFW households in all agricultural seasons. GM concentration of urinary DAPs
      was higher for children in FW households than NFW households. DISCUSSION:
      Regression analysis found a positive association between OP residues in house
      dust and the children's urinary DAPs. CONCLUSIONS: To our knowledge, this study
      is the first to report an association between pesticides in house dust and their
      biological metabolites in urine.

PMID- 29047309
TI  - Chimpanzee adenoviral vectors as vaccines - challenges to move the technology
      into the fast lane.
AB  - INTRODUCTION: In recent years, replication-defective chimpanzee-derived
      adenoviruses have been extensively evaluated as genetic vaccines. These vectors
      share desirable properties with human adenoviruses like the broad tissue tropism
      and the ease of large-scale manufacturing. Additionally, chimpanzee adenoviruses
      have the advantage to overcome the negative impact of pre-existing anti-human
      adenovirus immunity. Areas covered: Here the authors review current pre-clinical
      research and clinical trials that utilize chimpanzee-derived adenoviral vectors
      as vaccines. A wealth of studies are ongoing to evaluate different vector
      backbones and administration routes with the aim of improving immune responses.
      The challenges associated with the identification of an optimal chimpanzee vector
      and immunization strategies for different immunological outcomes will be
      discussed. Expert commentary: The demonstration that chimpanzee adenoviruses can
      be safely used in humans has paved the way to the use of a whole new array of
      vectors of different serotypes. However, so far no predictive signature of vector
      immunity in humans has been identified. The high magnitude of T cell responses
      elicited by chimpanzee adenoviruses has allowed dissecting the qualitative
      aspects that may be important for protective immunity. Ultimately, only the
      results from the most clinically advanced products will help establish the
      efficacy of the vaccine vector platform in the field of disease prevention.

PMID- 29047312
TI  - [Articles of the Hungarian Medical Journal from March, 2006].

PMID- 29047310
TI  - Reserve or Resident Progenitors in Cartilage? Comparative Analysis of
      Chondrocytes versus Chondroprogenitors and Their Role in Cartilage Repair.
AB  - Introduction Articular cartilage is made up of hyaline tissue embodying
      chondrocytes, which arise from mesenchymal stromal cells (MSCs) and specialized
      extracellular matrix. Despite possessing resident progenitors in and around the
      joint primed for chondrogenesis, cartilage has limited intrinsic capacity of
      repair and cell turnover. Advances in isolation, culture, and characterization of
      these progenitors have raised the possibility for their use in cell-based
      cartilage repair. Chondroprogenitors (CPCs) have been classified as MSCs and have
      been postulated to play a vital role in injury response and are identified by
      their colony forming ability, proliferative potential, telomere dynamics,
      multipotency, and expression of stem cell markers. The combined presence of CPCs
      and chondrocytes within the same tissue compartments and the ability of
      chondrocytes to dedifferentiate and acquire stemness during culture expansion has
      obscured our ability to define and provide clear-cut differences between these 2
      cell populations. Objective This review aims to evaluate and summarize the
      available literature on CPCs in terms of their origin, growth kinetics, molecular
      characteristics, and differential and therapeutic potential with emphasis on
      their difference from daughter chondrocytes. Design For this systematic review, a
      comprehensive electronic search was performed on PubMed and Google Scholar using
      relevant terms such as chondrocytes, chondroprogenitors, and surface marker
      expression. Results and Conclusion Our comparative analysis shows that there is
      an ill-defined distinction between CPCs and chondrocytes with respect to their
      cell surface expression (MSC markers and CPC-specific markers) and
      differentiation potential. Accumulating evidence indicates that the 2
      subpopulations may be distinguished based on their growth kinetics and
      chondrogenic marker.

PMID- 29047311
TI  - Catomentosaponin, a new triterpene saponin from the roots of Catunaregam
      tomentosa.
AB  - A new triterpene saponin, catomentosaponin (1) and 11 known analogues (2-12) were
      isolated from the roots of Catunaregam tomentosa. The structures of 1-12 were
      determined on the basis of extensive NMR and MS data analysis. The sugar residues
      were identified by co-TLC and HPLC analysis after hydrolysis. All isolated
      compounds were evaluated for their cytotoxicity against KB and HeLa cell lines.
      Compound 2 showed moderate cytotoxicity against KB cell with IC50 value of 24.84
      MUM.

PMID- 29047313
TI  - Two new hirsutane-type sesquiterpenoids chondrosterins N and O from the marine
      fungus Chondrostereum sp.
AB  - The marine fungus Chondrostereum sp. was collected from a soft coral Sarcophyton
      tortuosum from the South China Sea. This fungus was cultured in glucose-peptone
      yeast (GPY) medium and the culture broth was extracted with EtOAc. By the method
      of 1H NMR pre-screening and tracing the diagnostic proton signals of the methyl
      groups, two new hirsutane-type sesquiterpenoids, chondrosterins N and O (1 and 2)
      were isolated from the metabolite extracts. Their structures were elucidated on
      the basis of MS, 1D and 2D NMR data.

PMID- 29047314
TI  - Phytochemical investigation and acetylcholinesterase inhibitory activity of bark
      of Hymenodictyon orixense.
AB  - The chemical investigation of the methanol extract of Hymenodictyon orixense
      bark, a Thai medicinal herb, provided five compounds. Their structures were
      identified on the basis of 1D NMR and MS data, as well as by comparison of the
      data with published values, as an iridoid glycoside: loganin (1), four coumarins:
      scopoletin (2), scopolin (3), hymexelsin (4) and scopoletin 7-O-beta-D
      xylopyranosyl-(1->6)-beta-D-glucopyranoside (5). Compounds 1-5 showed
      acetylcholinesterase (AChE) inhibitory activity in the range of 13.92-34.18% at a
      concentration of 100 MUg/mL. In addition, compounds 1 and 5 are reported for the
      first time from this genus.

PMID- 29047315
TI  - In the presence of conflicting gaze cues, fearful expression and eye-size guide
      attention.
AB  - Humans are social beings that often interact in multi-individual environments. As
      such, we are frequently confronted with nonverbal social signals, including eye
      gaze direction, from multiple individuals. Yet, the factors that allow for the
      prioritisation of certain gaze cues over others are poorly understood. Using a
      modified conflicting gaze paradigm, we tested the hypothesis that fearful gaze
      would be favoured amongst competing gaze cues. We further hypothesised that this
      effect is related to the increased sclera exposure, which is characteristic of
      fearful expressions. Across three experiments, we found that fearful, but not
      happy, gaze guides observers' attention over competing non-emotional gaze. The
      guidance of attention by fearful gaze appears to be linked to increased sclera
      exposure. However, differences in sclera exposure do not prioritise competing
      gazes of other types. Thus, fearful gaze guides attention among competing cues
      and this effect is facilitated by increased sclera exposure - but increased
      sclera exposure per se does not guide attention. The prioritisation of fearful
      gaze over non-emotional gaze likely represents an adaptive means of selectively
      attending to survival-relevant spatial locations.

PMID- 29047316
TI  - Molecular analysis of haemoglobin E in Southeast Asian populations.
AB  - Haemoglobin (Hb) E is the most common Hb variant in Asia where its gene frequency
      approaches 0.3 in some areas. We studied genetic background of Hb E genes among
      Southeast Asian populations. This study examined beta-globin gene haplotypes
      linked to haemoglobin E (Hb E) in diverse groups of Southeast Asian populations.
      The study was conducted on southern Thai (22 alleles), Cambodian (84 alleles),
      Laotian (120 alleles), Vietnamese (87 alleles) and Burmese (one allele) subjects.
      Results were compared with those of previous studies in northeast Thailand, the
      Yunnan of China, West India and Europe. Ten different haplotypes were observed.
      The four most common haplotypes were haplotypes 1 (- + - + + + -) and 2 (+ - - - 
      + -) on chromosomes with framework 2 and haplotypes 6 (- + - + + - +) and 7 (+ -
      - - - - +) on chromosomes with framework 3 variety. Phylogenetic analysis
      indicated that haplotype 1 is a relatively recent haplotype found in all
      populations, whereas haplotype 6 is found predominately in Cambodians. The
      results indicate that at least two genetic origins of Hb E are responsible for
      the high prevalence and spread of Hb E among Southeast Asian populations.

PMID- 29047318
TI  - Spontaneous spinal epidural hemorrhage following disseminated intravascular
      coagulation resulting in paraplegia: a case report.
AB  - CONTEXT: Spontaneous spinal epidural hemorrhage (SSEH) mostly presents as low
      back pain with or without a radiculopathy, and rarely with paraplegia or
      tetraplegia depending on the site and severity of spinal cord compression. We
      present here a case who had anemia and developed paraplegia following
      disseminated intravascular coagulation (DIC) due to a transfusion reaction.
      FINDINGS: A 65-year-old lady presented with sudden onset chest pain radiating to
      nape of the neck followed by loss of sensations and power in legs few hours after
      a blood transfusion. Her past history was negative for diabetes mellitus,
      hypertension, coronary artery disease, or a bleeding disorder. Her blood pressure
      was 90/57 mmHg and she had a normal pulse, respiratory rate, and temperature. On
      neurological examination, she had no motor power and unevokable muscle stretch
      reflexes in the lower limbs. The sensations were intact till T3 dermatome. The
      laboratory evaluation was suggestive of DIC. The magnetic resonance imaging
      showed a non-enhancing abnormal signal intensity area in the posterior epidural
      space, extending from CV4 to LV4 causing cervico-dorsal cord compression
      associated with cord edema. Following diagnosis, urgent decompressive surgery was
      carried out due to deteriorating neurological status. The patient was transfused
      with five bags of red cell concentrate, two bags of platelets, and four bags of
      fresh frozen plasma during the operation. The patient regained consciousness
      following operation, however, the neurological status did not improve. She,
      unfortunately, died on the third post-op day due to cardiac arrest. CONCLUSION:
      SSEH is a rare cause of paraplegia. Early radiological diagnosis is crucial for
      timely neurosurgical management and saving patient from permanent neurological
      deficit or a fatal outcome.

PMID- 29047319
TI  - Hedge Fund Managers With Psychopathic Tendencies Make for Worse Investors.
AB  - It is widely assumed that psychopathic personality traits promote success in high
      powered, competitive contexts such as financial investment. By contrast,
      empirical studies find that psychopathic leaders can be charming and persuasive,
      but poor performers who mismanage, bully, and engage in unethical behavior. By
      coding nonverbal behaviors displayed in semistructured interviews, we identified
      the psychopathic, Machiavellian, and narcissistic tendencies in 101 hedge fund
      managers, and examined whether these traits were associated with financial
      performance over the course of 10 diverse years of economic volatility (2005
      2015). Managers with greater psychopathic tendencies produced lower absolute
      returns than their less psychopathic peers, and managers with greater
      narcissistic traits produced decreased risk-adjusted returns. The discussion
      focuses on the costs of Dark Triad traits in financial investment, and
      organizational leadership more generally.

PMID- 29047317
TI  - Varicella and herpes zoster vaccine development: lessons learned.
AB  - INTRODUCTION: Before vaccination, varicella zoster virus (VZV), which is endemic
      worldwide, led to almost universal infection. This neurotropic virus persists
      lifelong by establishing latency in sensory ganglia, where its reactivation is
      controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation
      (zoster) is around 30%. Vaccine development was galvanised by the economic and
      societal burden of VZV, including debilitating zoster complications that largely
      affect older individuals. Areas covered: We describe the story of development,
      licensing and implementation of live attenuated vaccines against varicella and
      zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune
      responses in the absence of suitable animal models and examine the changing
      epidemiology of VZV disease. We review the vaccines' efficacy, safety,
      effectiveness and coverage using evidence from trials, observational studies from
      large routine health datasets and clinical post-marketing surveillance studies
      and outline newer developments in subunit and inactivated vaccines. Expert
      commentary: Safe and effective, varicella and zoster vaccines have already made
      major inroads into reducing the burden of VZV disease globally. As these live
      vaccines have the potential to reactivate and cause clinical disease, developing
      alternatives that do not establish latency is an attractive prospect but will
      require better understanding of latency mechanisms.

PMID- 29047320
TI  - A trypsin inhibitor from Moringa oleifera flower extract is cytotoxic to
      Trypanosoma cruzi with high selectivity over mammalian cells.
AB  - In this study, Moringa oleifera flower extract and a trypsin inhibitor (MoFTI)
      isolated from it were evaluated for anti-protozoal activity against Trypanosoma
      cruzi and cytotoxicity to mammalian cells. The presence of flavonoids was
      remarkable in the HPLC fingerprints of the extract at 254 and 360 nm. Amino acid
      sequences of peptides derived from in-gel digestion of MoFTI were determined.
      Both the extract and MoFTI caused lysis of T. cruzi trypomastigotes with LC50/24
      h of 54.18 +/- 6.62 and 41.20 +/- 4.28 MUg/mL, respectively. High selectivity
      indices (7.9 to >12) for T. cruzi cells over murine peritoneal macrophages and
      Vero cells were found for the extract and MoFTI. The results show that MoFTI is a
      trypanocidal principle of the flower extract.

PMID- 29047321
TI  - Perioperative and Anesthetic Considerations in Pulmonary Atresia With Intact
      Ventricular Septum.
AB  - Pulmonary atresia with intact ventricular septum (PA/IVS) is a rare right-heart
      obstructive lesion with a wide anatomic and physiologic spectrum of disease,
      ranging from simple membranous pulmonary valve atresia with a fully developed
      right ventricle (RV) to a severely hypoplastic RV and ventriculocoronary (RV
      coronary) fistulas. Affected neonates are dependent on prostaglandin for adequate
      pulmonary blood flow. Depending on the severity of disease, treatment options
      range from transcatheter pulmonary valve perforation and ultimate biventricular
      repair to staged single-ventricle palliation. Cardiac transplantation is
      recommended in the most severe cases. This review will discuss the perioperative
      and anesthetic management of patients with PA/IVS and highlight the challenges in
      management.

PMID- 29047322
TI  - Trends in Primary Care Provision to Medicare Beneficiaries by Physicians, Nurse
      Practitioners, or Physician Assistants: 2008-2014.
AB  - OBJECTIVES: To document the temporal trends in alternative primary care models in
      which physicians, nurse practitioners (NPs), or physician assistants (PAs)
      engaged in care provision to the elderly, and examine the role of these models in
      serving elders with multiple chronic conditions and those residing in rural and
      health professional shortage areas (HPSAs). DESIGN: Serial cross-sectional
      analysis of Medicare claims data for years 2008, 2011, and 2014. SETTING: Primary
      care outpatient setting. PARTICIPANTS: Medicare fee-for-service beneficiaries who
      had at least 1 primary care office visit in each study year. The sample size is 2
      471 498. MEASUREMENTS: Physician model-Medicare beneficiary's primary care office
      visits in a year were conducted exclusively by physicians; shared care model
      conducted by a group of professionals that included physicians and either NPs or
      PAs or both; NP/PA model: conducted either by NPs or PAs or both. RESULTS: There
      was a decrease in the physician model (85.5% to 70.9%) and an increase in the
      shared care model (11.9% to 23.3%) and NP/PA model (2.7% to 5.9%) from 2008 to
      2014. Compared with the physician model, the adjusted odds ratio (AOR) of
      receiving NP/PA care was 3.97 (95% CI 3.80-4.14) in rural and 1.26 (95% CI 1.23
      1.29) in HPSAs; and the AOR of receiving shared care was 1.66 (95% CI 1.61-1.72)
      and 1.14 (95% CI 1.13-1.15), respectively. Beneficiaries with 3 or more chronic
      conditions were most likely to received shared care (AOR = 1.67, 95% CI 1.65
      1.70). CONCLUSION: The increase in shared care practice signifies a shift toward
      bolstering capacity of the primary care delivery system to serve elderly
      populations with growing chronic disease burden and to improve access to care in
      rural and HPSAs.

PMID- 29047323
TI  - Cooking Classes: A Diabetes Self-Management Support Intervention Enhancing
      Clinical Values.
AB  - Purpose The purpose of this study is to examine the relationship between Healthy
      Teaching Kitchen (HTK) attendance among veterans who are diagnosed with type 2
      diabetes mellitus (T2DM) and clinical outcomes as measured by A1C and blood
      pressure. Methods This retrospective chart review collected data from veterans
      with T2DM who participated in the Diabetes Self-Management Support (DSMS) HTK
      program at the Louis Stokes Cleveland VA Medical Center (LSCVAMC) between
      February 2013 and May 2016. Data collected included demographic information,
      frequency of DSMS HTK attendance, 3 A1C values, and 3 blood pressure values. Each
      subject was assigned to 1 of 4 quartiles based on frequency of DSMS HTK
      attendance. Results A1C values of all groups improved over time, regardless of
      DSMS HTK attendance quartile. However, as total DSMS HTK class attendance
      increased, there was a significant decrease in the A1C difference score.
      Conclusions Participation in a DSMS program that focuses on healthy, economical
      cooking skills may lead to a significant improvement in A1C regardless of
      frequency of attendance. However, individuals with more frequent attendance may
      experience additional improvement in glycemic control.

PMID- 29047324
TI  - Three-dimensional duck's feet collagen/PLGA scaffold for chondrification: role of
      pore size and porosity.
AB  - An ideal tissue-engineered scaffold must provide sufficient porosity to allow
      free movement of cells, nutrients, and oxygen for proper cell growth and further
      maintenance. Owing to variation in pore sizes and shapes of as-fabricated
      scaffold, the amount of oxygen available for the cells attached to the scaffold
      and transfer of by-products and excrement will be different, which ultimately
      results in cell activity. Thus, optimizing pore size and porosity of a scaffold
      for a specific tissue regeneration are one of the key highlights, which should be
      considered while designing a scaffold as well as choosing a specific cell type.
      In this study, three-dimensional (3D) scaffolds based on blends of duck's feet
      collagen (DC) and poly (lactic-co-glycolic acid) (PLGA) with different pore sizes
      i.e. 90-180, 180-250, 250-355 and 355-425 MUm were prepared using solvent
      casting/salt leaching approach and examined its effects on chondrification. The
      morphological analysis of the as-fabricated scaffolds was performed using SEM for
      studying porosity and pore size. The cell proliferation and gene expression were
      investigated after culturing costal chondrocytes on each scaffolds using 3-(4, 5
      dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay and qRT-PCR.
      Histological staining of in vivo implants was performed in nude mice as models.
      The biological evaluation showed a pore-size dependent chondrification at
      different time points. Especially, the 355-425 MUm DC/PLGA scaffold showed a
      highest positive impact on maintenance of cell proliferation, costal chondrocyte
      phenotype and increased glycosaminoglycan accumulation than the other groups.
      These results indicated that DC/PLGA scaffolds with pore size ranging from 250 to
      425 MUm can be considered as highly-suitable constructs for enhanced
      chondrification.

PMID- 29047325
TI  - Synthesis of BiOCl using Cl source from industrial wastewater and its application
      for wastewater treatment.
AB  - Cl- in industrial wastewater from glyphosate production has been used as Cl
      source to synthesize BiOCl photocatalyst via a simple solvothermal route. The
      crystalline, morphology, specific surface area and optical properties of
      photocatalysts prepared under various conditions have been investigated. BiOCl
      photocatalyst prepared in acidic solution shows the highest crystallinity and
      without impurities and microcellular structure. The degradation of industrial
      wastewater contaminants demonstrates the possibility of this BiOCl used in
      industrial wastewater treatment and phosphorus recycling through the subsequent
      phosphorus recovery processes. This study not only sheds light on the possibility
      of photocatalysts' preparation in situ using industrial wasterwater as raw
      materials and the feasibility of using photocatalysis technology in wastewater
      treatment area, but also the chloride ions have been removed as an available
      resource and the corrosion to treatment facilities has been slowed down. The
      phosphorus and nitrogen resources can be recycled by other subsequent recycle
      recoveries. It offers a novel way for the wastewater treatment process in
      succession from photocatalysts' manufacture to contaminants disposal.

PMID- 29047326
TI  - Integrating CHWs as Part of the Team Leading Diabetes Group Visits: A Randomized
      Controlled Feasibility Study.
AB  - Purpose The purpose of the study was to evaluate the feasibility of integrating
      Community Health Workers (CHWs) as part of the team leading diabetes group
      visits. Methods This was a randomized controlled study that integrated CHWs as
      part of the team leading diabetes group visits for low-income Hispanic adults (n
      = 50). Group visits met for 3 hours each month for a 6-month duration. Main
      measures included baseline and 6-month clinical outcomes (ie, A1C, lipids),
      concordance with 8 standard of care guidelines (ie, screens for cervical, breast,
      and colon cancer) from the US Preventive Task Force and American Diabetes
      Association, and participant acceptability. Results Compared to control
      participants, the intervention group resulted in significantly better clinical
      outcomes or guideline concordance for the following areas: target A1C levels,
      retinal eye exams, diabetes foot exams, mammograms, and urine microalbumin.
      Significantly more individuals in the control group gained weight, whereas a
      greater number of participants in the intervention group lost weight.
      Intervention participants found the group visits highly acceptable. Conclusions
      Integrating CHWs as part a comprehensive diabetes group visit program is a
      feasible and effective system-level intervention to improve glycemic control and
      achieve guideline concordance.

PMID- 29047327
TI  - Integrative testis transcriptome analysis reveals differentially expressed miRNAs
      and their mRNA targets during early puberty in Atlantic salmon.
AB  - BACKGROUND: Our understanding of the molecular mechanisms implementing pubertal
      maturation of the testis in vertebrates is incomplete. This topic is relevant in
      Atlantic salmon aquaculture, since precocious male puberty negatively impacts
      animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs
      relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs
      during initiation of puberty in salmon, we performed an integrated transcriptome
      analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an
      immature, long-term quiescent stage, a prepubertal stage just before, and a
      pubertal stage just after the onset of single cell proliferation activity in the
      testis. RESULTS: Differentially expressed miRNAs clustered into 5 distinct
      expression profiles related to the immature, prepubertal and pubertal salmon
      testis. Potential mRNA targets of these miRNAs were predicted with miRmap and
      filtered for mRNAs displaying negatively correlated expression patterns. In
      summary, this analysis revealed miRNAs previously known to be regulated in
      immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but
      also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c,
      miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the
      novel predicted n268). By KEGG enrichment analysis, progesterone signaling and
      cell cycle pathway genes were found regulated by these differentially expressed
      miRNAs. During the transition into puberty we found differential expression of
      miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184,
      miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment
      analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways
      were potential regulated targets during the transition into puberty. Likewise,
      several regulated miRNAs in the pubertal stage had earlier been associated (miR
      20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b, miR-222a/b, miR-190a) or
      have now been found connected (miR-2188, miR-144, miR-731, miR-8157 and the novel
      n2) to the initiation of puberty. CONCLUSIONS: This study has - for the first
      time - linked testis maturation to specific miRNAs and their inversely correlated
      expressed targets in Atlantic salmon. The study indicates a broad functional
      conservation of already known miRNAs and associated pathways involved in the
      transition into puberty in vertebrates. The analysis also reveals miRNAs not
      previously associated with testis tissue or its maturation, which calls for
      further functional studies in the testis.

PMID- 29047328
TI  - The modified pancreatic stent system for prevention of post-ERCP pancreatitis: a
      case-control study.
AB  - BACKGROUND: Prophylactic pancreatic stents after endoscopic retrograde
      cholangiopancreatography (ERCP) can help prevent post-ERCP pancreatitis. However
      most of the pancreatic stents need to be removed by another ERCP. The aim of this
      observational study was to investigate the feasibility and effectiveness of the
      modified pancreatic stent system for prevention of post-ERCP pancreatitis.
      METHODS: From November 2013 to November 2015, a total of 230 patients who had
      prophylactic pancreatic stent placed for prevention of post-ERCP pancreatitis at
      a single institution were identified and stratified. In this case-control design,
      150 patients received an ordinary pancreatic stent, and 80 patients received the
      modified pancreatic stent. The main outcome measures were the difficulty level
      and complications of pancreatic stent placement and extraction between the two
      groups. RESULTS: In ordinary group, the average time of pancreatic stent and
      nasal biliary drainage placement was 3.5 +/- 0.6 min. There were 13 cases of
      stent proximal migration (8.7%), 20 cases of stent spontaneous abscission
      (13.3%), 5 cases of acute pancreatitis (3.3%) (2 cases for stent abscission) and
      7 cases of hyperamylasemia (4.7%) after ERCP. One hundred thirty patients
      received extra duodenoscope (86.7%) to remove the stent, and 4 cases had acute
      pancreatitis and 5 patients had hyperamylasemia after removing the proximal
      migratory stents. In modified group, the average time of pancreatic stent system
      placement was 4.9 +/- 0.7 min, but there was only one case of stent abscission
      (1.3%), 2 cases of acute pancreatitis (2.5%) and 3 cases of hyperamylasemia
      (3.8%). The new pancreatic stents were removed directly under x-ray without
      complication. CONCLUSIONS: The modified pancreatic stent system has the same
      effect of preventing post-ERCP pancreatitis, lower rate of stents proximal
      migration and spontaneous abscission, and the advantage of easier removed
      compared with ordinary pancreatic stent.

PMID- 29047330
TI  - Deletion of the NR4A nuclear receptor NOR1 in hematopoietic stem cells reduces
      inflammation but not abdominal aortic aneurysm formation.
AB  - BACKGROUND: The NR4A3 orphan nuclear hormone receptor, NOR1, functions as a
      constitutively active transcription factor to regulate inflammation,
      proliferation, and cell survival during pathological vascular remodeling.
      Inflammatory processes represent key mechanisms leading to abdominal aortic
      aneurysm (AAA) formation. However, a role of NOR1 in AAA formation has not been
      investigated previously. METHODS: Inflammatory gene expression was analyzed in
      bone marrow-derived macrophages isolated from NOR1-deficient mice. Low-density
      lipoprotein receptor-deficient (LDLr-/-) mice were irradiated and reconstituted
      with hematopoietic stem cells obtained from NOR1-/- or wild-type littermate mice.
      Animals were infused with angiotensin II and fed a diet enriched in saturated fat
      to induce AAA formation. Quantification of AAA formation was performed by
      ultrasound and ex vivo measurements. RESULTS: Among 184 inflammatory genes that
      were analyzed, 36 genes were differentially regulated in LPS-treated NOR1
      deficient macrophages. Albeit this difference in gene regulation, NOR1-deficiency
      in hematopoietic stem cells did not affect development of AAA formation in bone
      marrow-derived stem cell transplanted LDLr-deficient mice. CONCLUSION: NOR1
      deletion induced differential inflammatory gene transcription in macrophages but
      did not influence AAA formation in mice.

PMID- 29047329
TI  - Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population
      structure, genomic and functional diverisity, and global distribution in
      mammalian gut microbiotas.
AB  - BACKGROUND: Akkermansia muciniphila is one of the most dominant bacteria that
      resides on the mucus layer of intestinal tract and plays key role in human
      health, however, little is known about its genomic content. RESULTS: Herein, we
      for the first time characterized the genomic architecture of A. muciniphila based
      on whole-genome sequencing, assembling, and annotating of 39 isolates derived
      from human and mouse feces. We revealed a flexible open pangenome of A.
      muciniphila currently consisting of 5644 unique proteins. Phylogenetic analysis
      identified three species-level A. muciniphila phylogroups exhibiting distinct
      metabolic and functional features. Based on the comprehensive genome catalogue,
      we reconstructed 106 newly A. muciniphila metagenome assembled genomes (MAGs)
      from available metagenomic datasets of human, mouse and pig gut microbiomes,
      revealing a transcontinental distribution of A. muciniphila phylogroups across
      mammalian gut microbiotas. Accurate quantitative analysis of A. muciniphila
      phylogroups in human subjects further demonstrated its strong correlation with
      body mass index and anti-diabetic drug usage. Furthermore, we found that, during
      their mammalian gut evolution history, A. muciniphila acquired extra genes,
      especially antibiotic resistance genes, from symbiotic microbes via recent
      lateral gene transfer. CONCLUSIONS: The genome repertoire of A. muciniphila
      provided insights into population structure, evolutionary and functional
      specificity of this significant bacterium.

PMID- 29047331
TI  - "I can't bend it and it hurts like mad": direct observation of gout consultations
      in routine primary health care.
AB  - BACKGROUND: Gout is the most common form of inflammatory arthritis and is
      associated with considerable co-morbidity. It is usually managed in the primary
      care setting with a combination of lifestyle modification and pharmacological
      therapy. This study describes patterns of communication about gout observed in
      interactions between patients and primary care practitioners during routine
      consultations. METHODS: Secondary analysis of video-recordings of individual
      healthcare consultations between patients and a range of primary care
      practitioners (including general practitioners, practice nurses, podiatrists and
      dietitians) from an archived database. Consultations that included any discussion
      about gout were eligible for inclusion (n = 31) and were not restricted to those
      where gout was the main presenting complaint. The consultation transcripts were
      analysed using a qualitative inductive approach from clinical and linguistic
      perspectives and supplemented with visual observation of the interactions.
      RESULTS: Two main themes emerged from the data; the importance of gout and
      'telling' versus 'listening' in consultations. The first theme had two distinct
      strands; gout as an incidental part of the consultation and the impact of gout on
      patients. A trend towards more didactic practitioner communication encompassed by
      the second theme occurred at many different consultation points including
      diagnosis, in more general post-diagnosis discussion, and when discussing
      biochemical test results and lifestyle advice. In contrast, when discussion about
      treatment with medicines occurred a tendency towards a greater degree of
      listening to patients was observed. CONCLUSION: Our observation of the
      communication patterns in these consultations illustrates an inherent complexity
      of gout consultations in primary care. Gout may be more important to patients
      than is often apparent to practitioners in routine consultations. Consultation
      management needs to take into account the impact of the condition and the balance
      of information provided around lifestyle advice versus long-term management with
      medicines.

PMID- 29047332
TI  - A set of systematic reviews to help reduce inappropriate prescribing to older
      people: study protocol.
AB  - BACKGROUND: Multimorbidity and polypharmacy are common in older people.
      Assessment tools or lists of criteria aimed at supporting prescription decisions
      for older people exist, but have often been based on expert opinion with
      insufficient consideration of the evidence available. The present paper describes
      the methods we are using to systematically review the existing evidence on the
      efficacy and safety of the most commonly prescribed drugs for older people in the
      management of their chronic medical conditions and to develop recommendations to
      reduce inappropriate prescriptions for incorporation into the Comprehensive
      Medication Review (CMR) tool developed by the PRIMA-eDS European project.
      METHODS: We selected the 20 most relevant drugs/drug classes in terms of
      prescription volumes and risk of hospitalisation for older people and the most
      relevant indications for the most common chronic conditions among older people
      and a total of 35 distinct drug-indication pairs were chosen. Based on clinical
      considerations we collapsed some indications together, reducing the 35 pairs to a
      final total of 22 separate systematic reviews (SR). A common methodology will be
      used for each individual SR, based on the methodological manuals of the Cochrane
      collaboration and the PRISMA statement for reporting systematic reviews. Our
      search strategy will have a staged approach where we initially search for
      systematic reviews and meta-analyses, but if relevant reviews are not found, then
      search for individual studies (controlled intervention and observational
      studies). Our pilot work and initial scoping of the literature suggested that
      very few, relevant individual trials or existing systematic reviews have
      researched or reported exclusively on older people. Therefore, sufficient data
      might not be available to perform meta-analysis but we will provide a narrative
      synthesis describing characteristics and findings of included studies. The
      collected evidence will be used to construct recommendations on when not to use
      or to discontinue a drug, or when to reduce its dose. Recommendations will be
      developed in team meetings using the GRADE methodology to reflect the strength of
      the recommendation and the quality of the evidence. Recommendations will be built
      into the CMR tool. DISCUSSION: This protocol has been prepared for a series of
      systematic reviews which will provide research-based evidence to develop
      recommendations to reduce inappropriate polypharmacy in older people as part of
      the CMR tool of the PRIMA-eDS project.

PMID- 29047333
TI  - Electrochemical performance and microbial community profiles in microbial fuel
      cells in relation to electron transfer mechanisms.
AB  - BACKGROUND: Microbial fuel cells (MFCs) operating with complex microbial
      communities have been extensively reported in the past, and are commonly used in
      applications such as wastewater treatment, bioremediation or in-situ powering of
      environmental sensors. However, our knowledge on how the composition of the
      microbial community and the different types of electron transfer to the anode
      affect the performance of these bioelectrochemical systems is far from complete.
      To fill this gap of knowledge, we designed a set of three MFCs with different
      constrains limiting direct and mediated electron transfer to the anode. RESULTS:
      The results obtained indicate that MFCs with a naked anode on which a biofilm was
      allowed unrestricted development (MFC-A) had the most diverse archaeal and
      bacterial community, and offered the best performance. In this MFC both, direct
      and mediated electron transfer, occurred simultaneously, but direct electron
      transfer was the predominant mechanism. Microbial fuel cells in which the anode
      was enclosed in a dialysis membrane and biofilm was not allowed to develop (MFC
      D), had a much lower power output (about 60% lower), and a prevalence of
      dissolved redox species that acted as putative electron shuttles. In the anolyte
      of this MFC, Arcobacter and Methanosaeta were the prevalent bacteria and archaea
      respectively. In the third MFC, in which the anode had been covered by a cation
      selective nafion membrane (MFC-N), power output decreased a further 5% (95% less
      than MFC-A). In this MFC, conventional organic electron shuttles could not
      operate and the low power output obtained was presumably attributed to
      fermentation end-products produced by some of the organisms present in the
      anolyte, probably Pseudomonas or Methanosaeta. CONCLUSION: Electron transfer
      mechanisms have an impact on the development of different microbial communities
      and in turn on MFC performance. Although a stable current was achieved in all
      cases, direct electron transfer MFC showed the best performance concluding that
      biofilms are the major contributors to current production in MFCs.
      Characterization of the complex microbial assemblages in these systems may help
      us to unveil new electrogenic microorganisms and improve our understanding on
      their role to the functioning of MFCs.

PMID- 29047334
TI  - A Support Vector Machine based method to distinguish long non-coding RNAs from
      protein coding transcripts.
AB  - BACKGROUND: In recent years, a rapidly increasing number of RNA transcripts has
      been generated by thousands of sequencing projects around the world, creating
      enormous volumes of transcript data to be analyzed. An important problem to be
      addressed when analyzing this data is distinguishing between long non-coding RNAs
      (lncRNAs) and protein coding transcripts (PCTs). Thus, we present a Support
      Vector Machine (SVM) based method to distinguish lncRNAs from PCTs, using
      features based on frequencies of nucleotide patterns and ORF lengths, in
      transcripts. METHODS: The proposed method is based on SVM and uses the first ORF
      relative length and frequencies of nucleotide patterns selected by PCA as
      features. FASTA files were used as input to calculate all possible features.
      These features were divided in two sets: (i) 336 frequencies of nucleotide
      patterns; and (ii) 4 features derived from ORFs. PCA were applied to the first
      set to identify 6 groups of frequencies that could most contribute to the
      distinction. Twenty-four experiments using the 6 groups from the first set and
      the features from the second set where built to create the best model to
      distinguish lncRNAs from PCTs. RESULTS: This method was trained and tested with
      human (Homo sapiens), mouse (Mus musculus) and zebrafish (Danio rerio) data,
      achieving 98.21%, 98.03% and 96.09%, accuracy, respectively. Our method was
      compared to other tools available in the literature (CPAT, CPC, iSeeRNA,
      lncRNApred, lncRScan-SVM and FEELnc), and showed an improvement in accuracy by
      ~3.00%. In addition, to validate our model, the mouse data was classified with
      the human model, and vice-versa, achieving ~97.80% accuracy in both cases,
      showing that the model is not overfit. The SVM models were validated with data
      from rat (Rattus norvegicus), pig (Sus scrofa) and fruit fly (Drosophila
      melanogaster), and obtained more than 84.00% accuracy in all these organisms. Our
      results also showed that 81.2% of human pseudogenes and 91.7% of mouse
      pseudogenes were classified as non-coding. Moreover, our method was capable of re
      annotating two uncharacterized sequences of Swiss-Prot database with high
      probability of being lncRNAs. Finally, in order to use the method to annotate
      transcripts derived from RNA-seq, previously identified lncRNAs of human, gorilla
      (Gorilla gorilla) and rhesus macaque (Macaca mulatta) were analyzed, having
      successfully classified 98.62%, 80.8% and 91.9%, respectively. CONCLUSIONS: The
      SVM method proposed in this work presents high performance to distinguish lncRNAs
      from PCTs, as shown in the results. To build the model, besides using features
      known in the literature regarding ORFs, we used PCA to identify features among
      nucleotide pattern frequencies that contribute the most in distinguishing lncRNAs
      from PCTs, in reference data sets. Interestingly, models created with two
      evolutionary distant species could distinguish lncRNAs of even more distant
      species.

PMID- 29047335
TI  - Candidate lethal haplotypes and causal mutations in Angus cattle.
AB  - BACKGROUND: If unmanaged, high rates of inbreeding in livestock populations
      adversely impact their reproductive fitness. In beef cattle, historical selection
      strategies have increased the frequency of several segregating fatal autosomal
      recessive polymorphisms. Selective breeding has also decreased the extent of
      haplotypic diversity genome-wide. By identifying haplotypes for which homozygotes
      are not observed but would be expected based on their frequency, candidates for
      developmentally lethal recessive loci can be localized. This analysis comes
      without the need for observation of the loss-associated phenotype (e.g., failure
      to implant, first trimester abortion, deformity at birth). In this study,
      haplotypes were estimated for 3961 registered Angus individuals using 52,545 SNP
      loci using findhap v2, which exploited the complex pedigree among the individuals
      in this population. RESULTS: Seven loci were detected to possess haplotypes that
      were not observed in homozygous form despite a sufficiently high frequency and
      pedigree-based expectation of homozygote occurrence. These haplotypes were
      identified as candidates for harboring autosomal recessive lethal alleles. Of the
      genotyped individuals, 109 were resequenced to an average 27X depth of coverage
      to identify putative loss-of-function alleles genome-wide and had variants called
      using a custom in-house developed pipeline. For the candidate lethal-harboring
      haplotypes present in these bulls, sequence-called genotypes were used to
      identify concordant variants. In addition, whole-genome sequence imputation of
      variants was performed into the set of 3961 genotyped animals using the 109
      resequenced animals to identify candidate lethal recessive variants at the seven
      loci. Following the imputation, no variants were identified that were fully
      concordant with the marker-based diplotypes. CONCLUSIONS: Selective breeding
      programs could utilize the predicted lethal haplotypes associated with SNP
      genotypes. Sequencing and other methods for identifying the causal variants
      underlying these haplotypes can allow for more efficient methods of management
      such as gene editing. These two methods in total will reduce the negative impacts
      of inbreeding on fertility and maximize overall genetic gains.

PMID- 29047336
TI  - A qualitative exploration of work-related head injury: vulnerability at the
      intersection of workers' decision making and organizational values.
AB  - BACKGROUND: Work-related head injury is a critical public health issue due to its
      rising prevalence; the association with profound disruption of workers' lives;
      and significant economic burdens in terms of medical costs and lost wages.
      Efforts to understand and prevent these types of injuries have largely been
      dominated by epidemiological research and safety science, which has focused on
      identifying risk at the level of the individual worker, population group, or
      organizational sector. Limited research has focused on the perspectives of the
      workers, a key stakeholder group for informing understanding of vulnerability to
      work-related head injury. This study explored workers' perspectives to better
      understand their decision-making and how and why their injuries occurred.
      METHODS: We conducted a qualitative study using in-depth semi-structured
      interviews with thirty-two adult workers who had sustained a work-related head
      injury. Workers were recruited from an urban clinic in central Ontario, Canada.
      Labour Process Theory informed the thematic analysis. RESULTS: Three hazardous
      work conditions were identified: insufficient training; inadequate staffing; and
      inattention to the physical environment. In addition, professional and
      organizational norms were implicated in vulnerability to head injury including
      putting the client before the worker and the pressure to work unsafely. The
      findings also highlight a complex interrelationship between workers' decision
      making and professional and organizational norms that produces vulnerability to
      head injury, a vulnerability which oftentimes is reproduced by workers' decisions
      to work despite hazardous conditions. CONCLUSIONS: Our findings suggest that,
      beyond the need to redress the inattention to hazards in the physical
      environment, there is a need to address norms that influence worker decision
      making to improve the safety of workers. Using Labour Process Theory highlights
      an important social dynamic within workplace sectors that could inform future
      development and implementation of multi-level and integrated public health
      strategies to reduce work-related head injury.

PMID- 29047337
TI  - Prevalence and incidence of musculoskeletal extremity complaints in children and
      adolescents. A systematic review.
AB  - BACKGROUND: It is difficult to gain an overview of musculoskeletal extremity
      complaints in childhood although this is essential to develop evidence-based
      prevention and treatment strategies. The objectives of this systematic review
      were therefore to describe the prevalence and incidence of musculoskeletal
      extremity complaints in children and adolescents in both general and clinical
      populations in relation to age, anatomical site and mode of onset. METHODS:
      MEDLINE and EMBASE were electronically searched; risk of bias was assessed; and
      data extraction was individually performed by two authors. RESULTS: In total, 19
      general population studies and three clinical population studies were included
      with children aged 0-19 years. For most of the analyses, a division between
      younger children aged 0-12 years, and older children aged 10-19 years was used.
      Lower extremity complaints were more common than upper extremity complaints
      regardless of age and type of population, with the most frequent pain site
      changing from ankle/foot in the youngest to knee in the oldest. There were about
      twice as many non-traumatic as traumatic complaints in the lower extremities,
      whereas the opposite relationship was found for the upper extremities in the
      general population studies. There were relatively more lower extremity complaints
      in the general population studies than in the clinical population studies. The
      review showed no pattern of differences in reporting between studies of high and
      low risk of bias. CONCLUSIONS: This review shows that musculoskeletal complaints
      are more frequent in the lower extremities than in the upper extremities in
      childhood, and there are indications of a large amount of non-traumatic low
      intensity complaints in the population that do not reach threshold for
      consultation. A meta-analysis, or even a simple overall description of prevalence
      and incidence of musculoskeletal extremity complaints in children and adolescents
      was not feasible, due to a large variety in the studies, primarily related to
      outcome measurements.

PMID- 29047338
TI  - Unique N-terminal sequences in two Runx1 isoforms are dispensable for Runx1
      function.
AB  - BACKGROUND: The Runt-related transcription factors (Runx) are a family of
      evolutionarily conserved transcriptional regulators that play multiple roles in
      the developmental control of various cell types. Among the three mammalian Runx
      proteins, Runx1 is essential for definitive hematopoiesis and its dysfunction
      leads to human leukemogenesis. There are two promoters, distal (P1) and proximal
      (P2), in the Runx1 gene, which produce two Runx1 isoforms with distinct N
      terminal amino acid sequences, P1-Runx1 and P2-Runx1. However, it remains unclear
      whether P2-Runx specific N-terminal sequence have any specific function for Runx1
      protein. RESULTS: To address the function of the P2-Runx1 isoform, we established
      novel mutant mouse models in which the translational initiation AUG (+1) codon
      for P2-Runx1 isoform was modulated. We found that a truncated P2-Runx1 isoform is
      translated from a downstream non-canonical AUG codon. Importantly, the truncated
      P2-Runx1 isoform is sufficient to support primary hematopoiesis, even in the
      absence of the P1-Runx1 isoform. Furthermore, the truncated P2-Runx1 isoform was
      able to restore defect in basophil development caused by loss of the P1-Runx1
      isoform. The truncated P2-Runx1 isoform was more stable than the canonical P2
      Runx1 isoform. CONCLUSIONS: Our results demonstrate that the N-terminal sequences
      specific for P2-Runx1 are dispensable for Runx1 function, and likely serve as a
      de-stabilization module to regulate Runx1 production.

PMID- 29047339
TI  - Exploring the evidence base for how people with dementia and their informal
      carers manage their medication in the community: a mixed studies review.
AB  - BACKGROUND: Little is known about the general medicines management issues for
      people with dementia living in the community. This review has three aims: firstly
      to explore and evaluate the international literature on how people with dementia
      manage medication; assess understanding of medicines management from an informal
      carers perspective; and lastly to understand the role that healthcare
      professionals play in assisting this population with medicines management.
      METHODS: A mixed studies review was conducted. Web of Knowledge, PubMed and
      Cochrane Library were searched post-1999 for studies that explored medicines
      management in people with dementia dwelling in the community, and the role
      healthcare professionals play in supporting medicines management in people with
      dementia. Following screening, nine articles were included. Data from included
      studies were synthesised using a convergent synthesis approach and analysed
      thematically to combine findings from studies using a range of methods
      (qualitative, quantitative and mixed methods). RESULTS: Four themes were
      generated from the synthesis: The nature of the disease and the effects this had
      on medicines management; the additional responsibilities informal carers have;
      informal caregivers' knowledge of the importance of managing medication and
      healthcare professionals' understanding of medicines management in people with
      dementia. Consequently, these were found to affect management of medication, in
      particular adherence to medication. CONCLUSIONS: This review has identified that
      managing medication for people with dementia dwelling in the community is a
      complex task with a frequently associated burden on their informal caregivers.
      Healthcare professionals can be unaware of this burden. The findings warrant the
      need for healthcare professionals to undergo further training in supporting
      medicines management for people with dementia in their own homes.

PMID- 29047340
TI  - Occupational blood exposures in health care workers: incidence, characteristics,
      and transmission of bloodborne pathogens in South Korea.
AB  - BACKGROUND: Health care workers (HCWs) are at high risk for occupational blood
      exposures (OBEs) and transmission of bloodborne pathogens. This study elucidated
      the incidence rate and epidemiological characteristics of OBEs among HCWs and
      investigated the pathogen transmission rate for hepatitis B virus (HBV),
      hepatitis C virus (HCV), and human immunodeficiency virus (HIV). METHODS: Self
      reported OBEs from January 1, 2011 to December 31, 2015 were obtained from the
      electronic recording system. OBE incidence densities per 100 person-years and per
      100 bed-years were calculated with a 5-year trend analysis. OBE characteristics
      and pathogen transmission rates were evaluated. RESULTS: Among 10,452 HCWs and
      1072 average yearly beds, 1076 OBEs were reported. OBE incidence rate was 5.6
      cases per 100 person (full-time equivalent)-years and 20.3 per 100 bed-years.
      Incidence rate decreased and was significantly associated with a decrease of beds
      served per HCW. Housekeeping showed the highest OBE rate (14.8%) followed by
      doctors (8.5%) and nurses (6.2%). OBEs occurred in wards, emergency rooms, and
      operating rooms (38.1%, 13.3% and 12.2%, respectively) via percutaneous (86.7%)
      and mucocutaneous exposures (13.2%). Of OBEs associated with HBV (n = 133), HCV
      (n = 126), and HIV (n = 25), only one led to an infection (HCV; transmission rate
      of 0.8%). Neither HBV nor HIV infection occurred. CONCLUSIONS: OBE incidence rate
      in a Korean university hospital was 5.6 cases per 100 person-years and 20.3 per
      100 bed-years and was related to HCW workload and work proficiency. Though the
      actual bloodborne pathogen transmission rate was low, efforts to prevent OBE
      should be made for hospital safety.

PMID- 29047341
TI  - Prevalence of multimorbidity in Germany: impact of age and educational level in a
      cross-sectional study on 19,294 adults.
AB  - BACKGROUND: Multimorbidity is one of the most important and challenging aspects
      in public health. Multimorbid people are associated with more hospital
      admissions, a large number of drug prescriptions and higher risks of mortality.
      As there is evidence that multimorbidity varies with age and socioeconomic
      disparity, the main objective aimed at determining age-specific prevalence rates
      as well as exploring educational differences relating to multimorbidity in
      Germany. METHODS: This cross-sectional analysis is based on the national
      telephone health interview survey "German Health Update" (GEDA2012) conducted
      between March 2012 and March 2013 with nearly 20,000 adults. GEDA2012 provides
      information on 17 self-reported health conditions along with sociodemographic
      characteristics. Multimorbidity was defined as the occurrence of two or more
      chronic conditions in one individual at the same time. Descriptive statistical
      analysis was used to examine multimorbidity according to age and education, which
      was defined by the International Standard Classification of Education (ISCED
      1997). RESULTS: Overall, 39.6% (95% confidence interval (CI) 38.7%-40.6%) of the
      19,294 participants were multimorbid and the proportion of adults with
      multimorbidity increased substantially with age: nearly half (49.2%, 95% CI 46.9%
      51.5%) of the adults aged 50-59 years had already two or more chronic health
      conditions. Prevalence rates of multimorbidity differed considerably between the
      levels of education. Low-level educated adults aged 40-49 years were more likely
      to be multimorbid with a prevalence rate of 47.4% (95% CI 44.2%-50.5%) matching
      those of highly educated men and women aged about ten years older. CONCLUSIONS:
      Our findings demonstrate that both, age and education are associated with a
      higher risk of being multimorbid in Germany. Hence, special emphasis in the
      development of new approaches in national public health and prevention programs
      on multimorbidity should be given to low-level educated people aged <65 years.

PMID- 29047343
TI  - Prevalence of congenital cytomegalovirus infection in symptomatic newborns under
      3 weeks in Tehran, Iran.
AB  - BACKGROUND: Cytomegalovirus (CMV) is a common cause of congenital infection
      worldwide and infants with symptomatic congenital CMV (cCMV) infection are at
      significantly increased risk of developing adverse long-term outcomes. This study
      aimed to determine the prevalence of cCMV infections in symptomatic infants under
      3 weeks in Tehran, IRAN and to evaluate the usefulness of serologic markers in
      these neonates. METHODS: Urine and serum samples of 100 symptomatic infants,
      under 3 weeks old, with clinical signs referred to Tehran medical centers from
      June 2013 to December 2014, were collected and tested for CMV-DNA and IgG/IgM
      antibody titers by PCR and ELISA, respectively. RESULTS: CMV-DNA was detected in
      urine of 58 cases, whereas only 20 cases had detectable CMV-IgM titers. All CMV
      IgM positive cases excreted CMV-DNA through their urine. Of the 100 patients,
      only 59 had CMV-IgG antibody and CMV-DNA was found in the urine of only 40 of
      them. CONCLUSIONS: We conclude that CMV is an important etiologic agent of
      congenital infections in symptomatic infants in Tehran, IRAN (prevalence: 58%)
      and CMV-DNA detection immediately after delivery is recommended for early
      treatment and reduction of post infection problems. Furthermore, our study showed
      that the serologic markers are unreliable for diagnosis of cCMV infection in
      infants. This is the first report of cCMV prevalence in symptomatic congenital
      infections in Iran showing similarity with the world averages.

PMID- 29047342
TI  - Effectiveness and patient safety of platelet aggregation inhibitors in the
      prevention of cardiovascular disease and ischemic stroke in older adults - a
      systematic review.
AB  - BACKGROUND: Platelet aggregation inhibitors (PAI) are among the most frequently
      prescribed drugs in older people, though evidence about risks and benefits of
      their use in older adults is scarce. The objectives of this systematic review are
      firstly to identify the risks and benefits of their use in the prevention and
      treatment of vascular events in older adults, and secondly to develop
      recommendations on discontinuing PAI in this population if risks outweigh
      benefits. METHODS: Staged systematic review consisting of three searches.
      Searches 1 and 2 identified systematic reviews and meta-analyses. Search 3
      included controlled intervention and observational studies from review-articles
      not included in searches 1 and 2. All articles were assessed by two independent
      reviewers regarding the type of study, age of participants, type of intervention,
      and clinically relevant outcomes. After data extraction and quality appraisal we
      developed recommendations to stop the prescribing of specific drugs in older
      adults following the Grading of Recommendations Assessment Development and
      Evaluation (GRADE) methodology. RESULTS: Overall, 2385 records were screened
      leading to an inclusion of 35 articles reporting on 22 systematic reviews and
      meta-analyses, 11 randomised controlled trials, and two observational studies.
      Mean ages ranged from 57.0 to 84.6 years. Ten studies included a subgroup
      analysis by age. Overall, based on the evaluated evidence, three recommendations
      were formulated. First, the use of acetylsalicylic acid (ASA) for primary
      prevention of cardiovascular disease (CVD) in older people cannot be recommended
      due to an uncertainty in the risk-benefit ratio (weak recommendation; low quality
      of evidence). Secondly, the combination of ASA and clopidogrel in patients
      without specific indications should be avoided (strong recommendation; moderate
      quality of evidence). Lastly, to improve the effectiveness and reduce the risks
      of stroke prevention therapy in older people with atrial fibrillation (AF) and a
      CHA2DS2-VASc score of >= 2, the use of ASA for the primary prevention of stroke
      should be discontinued in preference for the use of oral anticoagulants (weak
      recommendation; low quality of evidence). CONCLUSIONS: The use of ASA for the
      primary prevention of CVD and the combination therapy of ASA and clopidogrel for
      the secondary prevention of vascular events in older people may not be justified.
      The use of oral anticoagulants instead of ASA in older people with atrial
      fibrillation may be recommended. Further high quality studies with older adults
      are needed.

PMID- 29047344
TI  - Efficacy and safety of metformin in the management of type 2 diabetes mellitus in
      older adults: a systematic review for the development of recommendations to
      reduce potentially inappropriate prescribing.
AB  - BACKGROUND: Metformin is usually prescribed as first line therapy for type 2
      diabetes mellitus (DM2). However, the benefits and risks of metformin may be
      different for older people. This systematic review examined the available
      evidence on the safety and efficacy of metformin in the management of DM2 in
      older adults. The findings were used to develop recommendations for the
      electronic decision support tool of the European project PRIMA-eDS. METHODS: The
      systematic review followed a staged approach, initially searching for systematic
      reviews and meta-analyses first, and then individual studies when prior searches
      were inconclusive. The target population was older people (>=65 years old) with
      DM2. Studies were included if they reported safety or efficacy outcomes with
      metformin (alone or in combination) for the management of DM2 compared to
      placebo, usual or no treatment, or other antidiabetics. Using the evidence
      identified, recommendations were developed using GRADE methodology. RESULTS:
      Fifteen studies were included (4 intervention and 11 observational studies). In
      ten studies at least 80% of participants were 65 years or older and 5 studies
      reported subgroup analyses by age. Comorbidities were reported by 9 studies,
      cognitive status was reported by 4 studies and functional status by 1 study. In
      general, metformin showed similar or better safety and efficacy than other
      specific or non-specific active treatments. However, these findings were mainly
      based on retrospective observational studies. Four recommendations were developed
      suggesting to discontinue the use of metformin for the management of DM2 in older
      adults with risk factors such as age > 80, gastrointestinal complaints during the
      last year and/or GFR <=60 ml/min. CONCLUSIONS: On the evidence available, the
      safety and efficacy profiles of metformin appear to be better, and certainly no
      worse, than other treatments for the management of DM2 in older adults. However,
      the quality and quantity of the evidence is low, with scarce data on adverse
      events such as gastrointestinal complaints or renal failure. Further studies are
      needed to more reliably assess the benefits and risks of metformin in very old
      (>80), cognitively and functionally impaired older people.

PMID- 29047345
TI  - Visual prognosis better in eyes with less severe reduction of visual acuity one
      year after onset of Leber hereditary optic neuropathy caused by the 11,778
      mutation.
AB  - BACKGROUND: Patients with Leber hereditary optic neuropathy (LHON) have a
      progressive decrease of their visual acuity which can deteriorate to <0.1. Some
      patients can have a partial recovery of their vision in one or both eyes. One
      prognostic factor associated with a recovery of vision is an early-age onset. The
      purpose of this study was to determine other clinical factors that are predictive
      of a good visual recovery. METHODS: Sixty-one Japanese LHON patients, with the
      11,778 mutation and a mean age of 23.1 +/- 12.1 years at the onset, were studied.
      All patients were initially examined at an acute stage of LHON and were followed
      for 3 to 10 years. At 1 year after the onset, the lowest visual acuity was <0.1
      in all eyes. We studied the following parameters of patients with/without a final
      visual acuity of >= 0.2: sex; heavy consumption of cigarettes and alcohol; taking
      idebenone; mean age at onset; mean lowest visual acuity; and distribution of the
      lowest and the final visual acuity. RESULTS: Fifteen (24.6%) of the 61 patients
      or 25 (20.5%) of the 122 eyes had a recovery of their visual acuity to >= 0.2.
      The mean age at onset of these 15 patients with visual recovery to >= 0.2 was
      17.5 +/- 7.7 years, and that of the 46 patients without visual recovery to >= 0.2
      was 25.0 +/- 12.8 years (P = 0.02, Mann-Whitney U test). The mean lowest visual
      acuity of the 25 eyes with visual recovery >= 0.2 was 0.04, and that of the 97
      eyes without visual recovery to >= 0.2 was 0.015 (P < 0.001, Mann-Whitney U
      test). Fifty percent (15/30) of the eyes whose lowest visual acuity was >= 0.04
      during 1 year after the onset had a visual recovery to >= 0.2, while 11% (10/92)
      of the eyes whose the lowest visual acuity was <= 0.03 had a visual recovery to
      >= 0.2 (P < 0.001, chi 2 test). There were no significant differences in the
      other clinical factors. CONCLUSION: A final visual acuity of >= 0.2 was
      associated with a less severe reduction of the visual acuity at 1 year after the
      onset. Our findings can be used to predict the visual prognosis in LHON patients.

PMID- 29047346
TI  - Mapping eQTL by leveraging multiple tissues and DNA methylation.
AB  - BACKGROUND: DNA methylation is an important tissue-specific epigenetic event that
      influences transcriptional regulation of gene expression. Differentially
      methylated CpG sites may act as mediators between genetic variation and gene
      expression, and this relationship can be exploited while mapping multi-tissue
      expression quantitative trait loci (eQTL). Current multi-tissue eQTL mapping
      techniques are limited to only exploiting gene expression patterns across
      multiple tissues either in a joint tissue or tissue-by-tissue frameworks. We
      present a new statistical approach that enables us to model the effect of germ
      line variation on tissue-specific gene expression in the presence of effects due
      to DNA methylation. RESULTS: Our method efficiently models genetic and epigenetic
      variation to identify genomic regions of interest containing combinations of mRNA
      transcripts, CpG sites, and SNPs by jointly testing for genotypic effect and
      higher order interaction effects between genotype, methylation and tissues. We
      demonstrate using Monte Carlo simulations that our approach, in the presence of
      both genetic and DNA methylation effects, gives an improved performance (in terms
      of statistical power) to detect eQTLs over the current eQTL mapping approaches.
      When applied to an array-based dataset from 150 neuropathologically normal adult
      human brains, our method identifies eQTLs that were undetected using standard
      tissue-by-tissue or joint tissue eQTL mapping techniques. As an example, our
      method identifies eQTLs by leveraging methylated CpG sites in a LIM homeobox
      member gene (LHX9), which may have a role in the neural development. CONCLUSIONS:
      Our score test-based approach does not need parameter estimation under the
      alternative hypothesis. As a result, our model parameters are estimated only once
      for each mRNA - CpG pair. Our model specifically studies the effects of non
      coding regions of DNA (in this case, CpG sites) on mapping eQTLs. However, we can
      easily model micro-RNAs instead of CpG sites to study the effects of post
      transcriptional events in mapping eQTL. Our model's flexible framework also
      allows us to investigate other genomic events such as alternative gene splicing
      by extending our model to include gene isoform-specific data.

PMID- 29047347
TI  - The dynamics of smoking-related disturbed methylation: a two time-point study of
      methylation change in smokers, non-smokers and former smokers.
AB  - BACKGROUND: The evidence for epigenome-wide associations between smoking and DNA
      methylation continues to grow through cross-sectional studies. However, few large
      scale investigations have explored the associations using observations for
      individuals at multiple time-points. Here, through the use of the Illumina 450K
      BeadChip and data collected at two time-points separated by approximately 7
      years, we investigate changes in methylation over time associated with quitting
      smoking or remaining a former smoker, and those associated with continued
      smoking. RESULTS: Our results indicate that after quitting smoking the most rapid
      reversion of altered methylation occurs within the first two decades, with
      reversion rates related to the initial differences in methylation. For 52 CpG
      sites, the change in methylation from baseline to follow-up is significantly
      different for former smokers relative to the change for never smokers (lowest p
      value 3.61 x 10-39 for cg26703534, gene AHRR). Most of these sites' respective
      regions have been previously implicated in smoking-associated diseases. Despite
      the early rapid change, dynamism of methylation appears greater in former smokers
      vs never smokers even four decades after cessation. Furthermore, our study
      reveals the heterogeneous effect of continued smoking: the methylation levels of
      some loci further diverge between smokers and non-smokers, while others re
      approach. Though intensity of smoking habit appears more significant than
      duration, results remain inconclusive. CONCLUSIONS: This study improves the
      understanding of the dynamic link between cigarette smoking and methylation,
      revealing the continued fluctuation of methylation levels decades after smoking
      cessation and demonstrating that continuing smoking can have an array of effects.
      The results can facilitate insights into the molecular mechanisms behind smoking
      induced disturbed methylation, improving the possibility for development of
      biomarkers of past smoking behavior and increasing the understanding of the
      molecular path from exposure to disease.

PMID- 29047349
TI  - Professional identity, career choices, and working conditions of future and young
      dentists in Germany - study design and methods of a nationwide comprehensive
      survey.
AB  - BACKGROUND: Little is known regarding young and future dentists' career choices,
      professional identity, and working conditions in Germany. While the dental
      healthcare environment and demands in treatment are changing, it remains unclear
      what job perceptions young dentists have developed at the beginning of their work
      life and if and how these perceptions change during the subsequent years. The aim
      of this study was to survey future and young dentists regarding their
      professional identity, planned career paths, and working conditions and strains
      to understand career decisions and choices and enable policy makers to include
      future dentists' views and expectations in their decisions. METHODS/DESIGN: This
      study is a longitudinal nationwide survey over a time span of 4 years of dental
      students and young dentists in Germany and is comprised of three waves. The first
      wave focuses on dental students in their final year before the state examination
      and is composed of a qualitative pre-study in the form of focus groups and a
      quantitative main survey in the form of a questionnaire. The end points were
      established to analyse (1) the professional identity of the young future
      dentists; (2) their career paths, preparation for a career, and basic career
      conditions; and (3) perceived conditions and strains. The aim of the overall
      survey was to depict the development of these three aspects during the first
      years of work life. All of the questions were evaluated with a descriptive
      univariate analysis. The analysed subgroups were grouped according to gender,
      target working condition (employed/self-employed), and primary socialisation
      (parents dentists/parents not dentists). DISCUSSION: To our knowledge, this is
      the only study which focuses on career choices, professional identity, and
      working conditions of future and young dentists in Germany. The longitudinal
      observation provides information that is essential for professional and purposive
      dental health care planning, and to meet the oral health demands and needs of the
      German population appropriately over the long term. TRIAL REGISTRATION: German
      Health Services Research Data Bank VfD_Y-Dent_14_003759 .

PMID- 29047348
TI  - Effectiveness and safety of vitamin K antagonists and new anticoagulants in the
      prevention of thromboembolism in atrial fibrillation in older adults - a
      systematic review of reviews and the development of recommendations to reduce
      inappropriate prescribing.

PMID- 29047352
TI  - Correction to: Evaluating the impact of a walking program in a disadvantaged
      area: using the RE-AIM framework by mixed methods.

PMID- 29047350
TI  - Sequence variants identification at the KCNQ1OT1:TSS differentially Methylated
      region in isolated omphalocele cases.
AB  - BACKGROUND: Omphalocele is a congenital midline ventral body wall defect that can
      exist as isolated malformation or as part of a syndrome. It can be considered one
      of the major and most frequent clinical manifestation of Beckwith-Wiedemann
      Syndrome (BWS) in case of loss of methylation at KCNQ1OT1: Transcription Star
      Site-Differentially Methylated Region (TSS-DMR) or in presence of CDKN1C
      mutations. The isolated form of the omphalocele accounts approximately for about
      the 14% of the total cases and its molecular etiology has never been fully
      elucidated. METHODS: Given the tight relationship with BWS, we hypothesized that
      the isolated form of the omphalocele could belong to the heterogeneous spectrum
      of the BWS associated features, representing an endophenotype with a clear
      genetic connection. We therefore investigated genetic and epigenetic changes
      affecting BWS imprinted locus at 11p15.5 imprinted region, focusing in particular
      on the KCNQ1OT1:TSS DMR. RESULTS: We studied 21 cases of isolated omphalocele
      detected during pregnancy or at birth and identified the following rare
      maternally inherited variants: i) the non-coding variant G > A at nucleotide 687
      (NR_002728.3) at KCNQ1OT1:TSS-DMR, which alters the methylation pattern of the
      imprinted allele, in one patient; ii) the deletion c.624-629delGGCCCC at exon 1
      of CDKN1C, with unknown clinical significance, in two unrelated cases.
      CONCLUSIONS: Taken together, these findings suggest that KCNQ1OT1:TSS-DMR could
      be a susceptibility locus for the isolated omphalocele.

PMID- 29047351
TI  - Lifestyle factors are significantly associated with the locomotive syndrome: a
      cross-sectional study.
AB  - BACKGROUND: The Japanese Orthopedic Association first proposed the concept of
      "locomotive syndrome" in 2007. It refers to circumstances in which elderly people
      need nursing care services or are at high risk of requiring such services within
      a short time. Recently, the public health burden of providing nursing care for
      elderly individuals has increased. Therefore, locomotive syndrome, and the means
      of preventing it, are a major public health focus in Japan. The purpose of this
      study was to investigate the relationships of lifestyle factors, such as smoking,
      alcohol consumption, sleep duration, and dental health, with locomotive syndrome.
      METHODS: We conducted a cross-sectional study using an internet panel survey. The
      participants comprised 747 individuals aged 30-90 years. Factors related to
      demographics (age, sex), general health (number of teeth, presence of periodontal
      disease), and lifestyle (smoking, alcohol consumption, sleep duration) were
      assessed. We also used the 25-question Geriatric Locomotive Function Scale to
      determine whether each participant had locomotive syndrome. Multivariate analysis
      was conducted using logistic regression to investigate the independent
      relationships between locomotive syndrome and lifestyle factors after adjusting
      for sex and age. RESULTS: A greater proportion of women (17.7%) than men (11.2%)
      had locomotive syndrome (p < 0.05). Participants aged >=65 years showed
      significantly higher percentages (men: 21.4%, women: 75.7%) of locomotive
      syndrome compared with those aged <65 years (p < 0.05). Logistic regression
      analysis revealed that older age (>= 65 years), sex, current smoking status,
      number of existing teeth, and presence of periodontal disease were associated
      with locomotive syndrome, whereas sleep duration was not. The frequency of
      alcohol consumption, except for daily drinking, was also associated with
      locomotive syndrome. CONCLUSION: Our study indicates that lifestyle factors, such
      as smoking and number of existing teeth, may partly affect the prevalence of
      locomotive syndrome. Hence, lifestyle modifications, such as improving oral
      hygiene and promoting cessation of smoking, are important means to reduce the
      risk of locomotive syndrome and should be promoted by public health staff.

PMID- 29047354
TI  - Using risk-tracing snowball approach to increase HIV case detection among high
      risk populations in Cambodia: an intervention study.
AB  - BACKGROUND: Early HIV diagnosis and initiation onto antiretroviral therapy may
      prevent ongoing spread of HIV. Risk Tracing Snowball Approach (RTSA) has been
      shown to be effective in detecting new HIV cases in other settings. The main
      objective of this study is to evaluate the effectiveness of RTSA in increasing
      the rate of newly identified HIV cases among high-risk populations. Our second
      objective was to evaluate the effectiveness of RTSA, as compared to the walk-in
      group, in increasing the number of HIV tests and early case detection. METHODS:
      This study was conducted from April 1 to September 30, 2016 at two NGO clinics in
      Phnom Penh, Cambodia. Respondent driven sampling method was adapted to develop
      RTSA to reach high-risk populations, including key populations and the general
      population who have social connections with key populations. Bivariate and
      multivariate logistic regression analyses were conducted. RESULTS: During the
      implementation period, 721 clients walked in for HIV testing (walk-in group), and
      all were invited to be seeds. Of the invited clients, 36.6% agreed to serve as
      seeds. Throughout the implementation, 6195 coupons were distributed to seeds or
      recruiters, and resulted in 1572 clients visiting the two clinics with coupons
      (RTSA group), for a coupon return rate of 25.3%. The rate of newly identified HIV
      cases among the RTSA group was significantly lower compared to that in walk-in
      group. However, the highest number of newly identified HIV cases was found during
      the implementation period, compared to both pre- and post-implementation period.
      Although statistically not significant, the mean CD4 count of newly identified
      HIV cases detected through RTSA was almost 200 cells/mm3 higher than that in the
      walk-in group. CONCLUSIONS: Although the rate of newly identified HIV cases among
      the RTSA group was lower than that in the walk-in group, the inclusion of RTSA in
      addition to the traditional walk-in method boosted new HIV case detection in the
      two participating clinics. A higher mean CD4 count for the RTSA group may reveal
      that RTSA may be able to detect HIV cases earlier than the traditional walk-in
      approach. Further research is needed to understand whether RTSA is a cost
      effective intervention to prevent ongoing spread of the HIV among high-risk
      populations in Cambodia.

PMID- 29047353
TI  - Precision medicine for all? Challenges and opportunities for a precision medicine
      approach to critical illness.
AB  - All of medicine aspires to be precise, where a greater understanding of
      individual data will lead to personalized treatment and improved outcomes.
      Prompted by specific examples in oncology, the field of critical care may be
      tempted to envision that complex, acute syndromes could bend to a similar
      reductionist philosophy-where single mutations could identify and target our
      critically ill patients for treatment. However, precision medicine faces many
      challenges in critical care. These include confusion about terminology,
      uncertainty about how to divide patients into discrete groups, the challenges of
      multi-morbidity, scale, and the need for timely interventions. This review
      addresses these challenges and provides a translational roadmap spanning
      preclinical work to identify putative treatment targets, novel designs for
      clinical trials, and the integration of the electronic health record to implement
      precision critical care for all.

PMID- 29047355
TI  - Hyperdynamic CSF motion profiles found in idiopathic normal pressure
      hydrocephalus and Alzheimer's disease assessed by fluid mechanics derived from
      magnetic resonance images.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) does not only ascertain
      morphological features, but also measures physiological properties such as fluid
      velocity or pressure gradient. The purpose of this study was to investigate
      cerebrospinal fluid (CSF) dynamics in patients with morphological abnormalities
      such as enlarged brain ventricles and subarachnoid spaces. We used a time
      resolved three dimensional phase contrast (3D-PC) MRI technique to quantitatively
      evaluate CSF dynamics in the Sylvian aqueduct of healthy elderly individuals and
      patients with either idiopathic normal pressure hydrocephalus (iNPH) or
      Alzheimer's disease (AD) presenting with ventricular enlargement. METHODS:
      Nineteen healthy elderly individuals, ten iNPH patients, and seven AD patients
      (all subjects >= 60 years old) were retrospectively evaluated 3D-PC MRI. The CSF
      velocity, pressure gradient, and rotation in the Sylvian aqueduct were quantified
      and compared between the three groups using Kolmogorov-Smirnov and Mann-Whitney U
      tests. RESULTS: There was no statistically significant difference in velocity
      among the three groups. The pressure gradient was not significantly different
      between the iNPH and AD groups, but was significantly different between the iNPH
      group and the healthy controls (p < 0.001), and similarly, between the AD group
      and the healthy controls (p < 0.001). Rotation was not significantly different
      between the iNPH and AD groups, but was significantly different between the iNPH
      group and healthy controls (p < 0.001), and similarly, between the AD group and
      the healthy controls (p < 0.001). CONCLUSIONS: Quantitative analysis of CSF
      dynamics with time resolved 3D-PC MRI revealed differences and similarities in
      the Sylvian aqueduct between healthy elderly individuals, iNPH patients, and AD
      patients. The results showed that CSF motion is in a hyperdynamic state in both
      iNPH and AD patient groups compared to healthy elderly individuals, and that iNPH
      patients and AD patients display similar CSF motion profiles.

PMID- 29047356
TI  - Non-syndromic cardiac progeria in a patient with the rare pathogenic p.Asp300Asn
      variant in the LMNA gene.
AB  - BACKGROUND: Mutations in LMNA gene, encoding Lamin A/C, cause a diverse array of
      phenotypes, collectively referred to as laminopathies. The most common
      manifestation is dilated cardiomyopathy (DCM), occurring in conjunction with
      variable skeletal muscle involvement but without involvement of the coronary
      arteries. Much less commonly, LMNA mutations cause progeroid syndromes, whereby
      an early-onset coronary artery disease (CAD) is the hallmark of the disease. We
      report a hitherto unreported compound cardiac phenotype, dubbed as "non-syndromic
      cardiac progeria", in a young patient who carried a rare pathogenic variant in
      the LMNA gene and developed progressive degeneration of various cardiac
      structures, as seen in the elderly. The phenotype resembled the progeroid
      syndromes, except that it was restricted to the heart and did not involve other
      organs. CASE PRESENTATION: The patient was a well-developed Caucasian female who
      presented at age 29 years with an acute myocardial infarction (MI) and was found
      to have extensive CAD. She had none of the conventional risk factors for
      atherosclerosis. She underwent coronary artery bypass surgery but continued to
      require multiple percutaneous coronary interventions for symptomatic obstructive
      coronary lesions. During the course of next 10 years, she developed mitral
      regurgitation, degenerative mitral and aortic valve diseases, atrial flutter, and
      progressive conduction defects. She died from progressive heart failure with
      predominant involvement of the right ventricle and severe tricuspid
      regurgitation. Cardiac phenotype in this young patient resembled degenerative
      cardiac diseases of the elderly and the progeroid syndromes. However, in contrast
      to the progeroid syndromes, the phenotype was restricted to the heart and did not
      involve other organs. Thus, the phenotype was dubbed as a non-syndromic cardiac
      progeria. Genetic screening of several cardiomyopathy genes, including LMNA,
      which is a causal gene for progeroid syndromes, led to identification of a very
      rare pathogenic p.Asp300Asn variant in the LMNA gene. CONCLUSIONS: We infer that
      the LMNA p.Asp300Asn mutation is pathogenic in non-syndromic cardiac progeria.
      Mutations involving codon 300 in the LMNA gene have been associated with
      progeroid syndromes involving multiple organs. Collectively, the data provide
      credence to the causal role of p.Asp300Asn mutation in the pathogenesis of non
      syndromic cardiac progeria.

PMID- 29047357
TI  - Effects of inbreeding and other systematic effects on fertility of Black Forest
      Draught horses in Germany.
AB  - BACKGROUND: The Black Forest Draught horse (BFDH) is an endangered German
      coldblood breed with its origin in the area of the Black Forest in South Germany.
      In this retrospective study, the influence of the inbreeding coefficient on
      foaling rates was investigated using records from ten breeding seasons. Due to
      the small population size of BFDH, the level of inbreeding is increasing and may
      have an effect on foaling rates.The data of the present study included all
      coverings reported for 1024 BFDH mares in the years 2001-2009. These mares were
      covered by 32 BFDH stallions from the State Stud Marbach. Data from 4534 estrus
      cycles was used to calculate per cycle foaling rate (CFR). Pedigree data
      contained all studbook data up to the foundation of the breed as early as 1836.
      The level of inbreeding of the mare, stallion and expected foal along with other
      systematic effects on CFR were analysed using a generalized linear mixed model
      approach. Stallion was employed as a random effect. Systematic fixed effects were
      month of mating, mating type, age of the mare and stallion, reproductive status
      of the mare and stallion line of the mare. Inbreeding coefficients of the
      stallion, mare and expected foal were modelled as linear covariates. RESULTS: The
      average CFR was 40.9%. The mean inbreeding coefficients of the mares, stallions
      and expected foals were 7.46, 7.70 and 9.66%. Mating type, age of the mare,
      reproductive status of the mare and stallion line of the mare had a significant
      effect. CONCLUSIONS: The results showed that the mating type, stallion line of
      the mare, sire, age and reproductive status of the mare exerted the largest
      influences on CFR in BFDH. Inbreeding coefficients of the stallion, mare and
      expected foal were not significantly related with CFR.

PMID- 29047358
TI  - Erratum to: Immunomodulation after ischemic stroke: potential mechanisms and
      implications for therapy.

PMID- 29047359
TI  - Thiazides in the management of hypertension in older adults - a systematic
      review.
AB  - BACKGROUND: Thiazides are commonly prescribed to older people for the management
      of hypertension. The objective of this study was to identify the evidence on the
      risks and benefits of their use among adults aged >=65 years and to develop
      recommendations to reduce potentially inappropriate use. METHODS: Systematic
      review (SR) of the literature covering six databases. We applied a staged search
      approach, where each search was undertaken only if the previous one did not yield
      high quality results. Searches 1 and 2 identified relevant SRs and meta-analyses
      published up to December 2015 from all databases. Search 3 identified additional
      individual interventional studies (IS) and observational studies (OS) not
      identified by the preceding searches. We included all studies evaluating the
      effect of thiazides on patient-relevant outcomes in the management of
      hypertension with a sufficient number of participants aged >=65 years or a
      subgroup analysis based on age. Two independent reviewers extracted data and
      carried out quality appraisal. Recommendations were developed using the GRADE
      methodology. RESULTS: Searches 1 to 3 were performed. We included 34 articles
      reporting on 12 IS and 4 OS. Mean ages ranged from 59 to 83.8 years. Four studies
      had performed a subgroup analysis by age. Information on comorbidity,
      polypharmacy and frailty of the participants was scarce or not available. The IS
      compared thiazides to placebo or other antihypertensive drugs and evaluated
      cardiovascular endpoints or all-cause-mortality as primary outcomes. The OS
      investigated the association between thiazide use and the risk of gout, fractures
      and adverse effects. Our results suggest that thiazides are efficacious in
      preventing cardiovascular events for this population group. Low-dose regimens of
      thiazides may be safer than high-dose (low quality of evidence), and a history of
      gout may increase the risk of adverse events (low quality of evidence). Three
      recommendations were developed. CONCLUSIONS: The use of low dose treatment with
      thiazides for the management of hypertension in adults aged 65 and older seems
      justified, unless a history of gout is present. The quality of the evidence is
      low and studies rarely describe characteristics of the participants such as
      polypharmacy and frailty. Further good quality studies are needed.

PMID- 29047360
TI  - Comparison of circulating dendritic cell and monocyte subsets at different stages
      of atherosclerosis: insights from optical coherence tomography.
AB  - BACKGROUND: While specific patterns of circulating dendritic cells (DCs) and
      monocytes are associated with the incidence of coronary artery disease, the
      characterization of circulating DC and monocyte subsets in patients with
      different stages of atherosclerosis remains unclear. METHODS: Forty-eight
      patients with unstable angina pectoris (UAP) diagnosed by angiography were
      enrolled. Likewise, 31 patients with ST-segment elevation myocardial infarction
      (STEMI) were enrolled and confirmed with the presence of thrombosis by
      angiography. Plaque features of 48 UAP patients were evaluated at the culprit
      lesions by OCT. Circulating myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and
      monocyte subsets were analyzed using flow cytometry. RESULTS: The proportions and
      absolute counts of mDC2s, which specifically express CD141 and possess the
      ability to activate CD8+ T lymphocytes, significantly decreased in patients with
      UAP and STEMI when compared with controls (0.08 * 104 +/- 0.05 * 104/ml and 0.08
      * 104 +/- 0.06 * 104/ml vs. 0.11 * 104 +/- 0.06 * 104/ml, p = 0.027). On the
      other hand, patients with UAP and STEMI had significantly higher proportions and
      counts of Mon2 subsets. In the OCT subgroup, patients with thin-cap fibroatheroma
      (TCFA) had higher proportions and absolute number of Mon2 (11.96% +/- 4.27% vs.
      9.42% +/- 4.05%, p = 0.034; 5.17 * 104/ml +/- 1.92 * 104/ml vs. 3.53 * 104/ml +/-
      2.65 * 104/ml, p = 0.045) than those without TCFA. However, there was no
      remarkable difference in mDC2s between patients with and without TCFA.
      CONCLUSIONS: Circulating Mon2 appears to be a promising marker for the severity
      of atherosclerotic plaque.

PMID- 29047361
TI  - Cross-cultural validation of simplified Chinese version of spine functional
      index.
AB  - BACKGROUND: No effective constructs were available in mainland China to assess
      the whole spine function. The SFI was developed to evaluate spinal function based
      on the concept of a single kinetic chain concept for whole spine. The SFI has
      been translated to Spanish and Turkish with accepted psychometric properties. It
      is imperative to introduce the SFI in mainland China and further to explore the
      measurement properties. METHODS: The English versions of the SFI was cross
      culturally translated according to international guidelines. Measurement
      properties (content validity, construct validity and reliability) were tested in
      accordance with the COSMIN checklists. A total of 271 patients were included in
      this study, and 61 participants with neck pain and 64 participants with back pain
      paid a second visit three to seven days later. Confirmatory factor analysis (CFA)
      and principal factor analysis (PCA) were applied to test the factor structure.
      The Functional Rating Index (FRI), Neck Disability Index (NDI), Oswestry
      Disability Index (ODI), SF-12 and a Visual Analogue Scale (VAS) were employed to
      evaluate the construct validity. Cronbach's alpha and an intra-class correlation
      coefficient (ICC) were calculated for internal consistency and reproducibility.
      RESULTS: The means score of SC-SFI was 63.60 in patients with spinal
      musculoskeletal disorders. A high response rate was acquired (265/271). No item
      was removed due to abnormal distribution or low item-total correlation. Results
      of CFA did not support that one-factor structure was in goodness of fit (CMIN/DF
      = 3.306, NNFI = 0.687, CFI = 0.756, GFI = 0.771 and RMSEA = 0.092). Yet, PCA
      suggested a one-factor structure was the best, accounting for 32% of the total
      variance. For structural validity, the SC-SFI correlated highly with the FRI,
      NDI, ODI, and PF, BP in SF-12 (r = 0.661, 0.610, 0.750, 0.709, 0.605,
      respectively). All the a priori hypotheses were verified. The Cronbach's alpha
      for the SC-SFI was 0.91, and ICC was 0.96 (95% CI, 0.94-0.98). Bland-Altman plot
      also confirmed excellent test-retest reliability. CONCLUSIONS: The SFI has been
      culturally adapted into SC-SFI with remarkable clinical acceptance, excellent
      internal consistency, reproducibility, and construct validity when applied to
      patients with spinal musculoskeletal disorders. The results of current study
      suggest that SC-SFI can be applied by physicians and researchers to measure whole
      spine functional status in mainland China.

PMID- 29047362
TI  - The GREENH-City interventional research protocol on health in all policies.
AB  - BACKGROUND: This paper presents the research protocol of the GoveRnance for
      Equity, EnviroNment and Health in the City (GREENH-City) project funded by the
      National Institute for Cancer (Subvention N degrees 2017-003-INCA). In France,
      health inequities have tended to increase since the late 1980s. Numerous studies
      show the influence of social, economic, geographic and political determinants on
      health inequities across the life course. Exposure to environmental factors is
      uneven across the population and may impact on health and health inequities. In
      cities, green spaces contribute to creating healthy settings which may help
      tackle health inequities. Health in All Policies (HiAP) represents one of the key
      strategies for addressing social and environmental determinants of health
      inequities. The objective of this research is to identify the most promising
      interventions to operationalize the HiAP approaches at the city level to tackle
      health inequities through urban green spaces. It is a participatory
      interventional research to analyze public policy in real life setting (WHO
      Healthy Cities). METHOD/DESIGN: It is a mixed method systemic study with a
      quantitative approach for the 80 cities and a comparative qualitative multiple
      case-studies of 6 cities. The research combines 3 different lens: 1/a political
      analysis of how municipalities apply HiAP to reduce social inequities of health
      through green space policies and interventions 2/a geographical and topological
      characterization of green spaces and 3/ on-site observations of the use of green
      spaces by the inhabitants. RESULTS: City profiles will be identified regarding
      their HiAP approaches and the extent to which these cities address social
      inequities in health as part of their green space policy action. The analysis of
      the transferability of the results will inform policy recommendations in the rest
      of the Health City Network and widely for the French municipalities.
      DISCUSSION/CONCLUSION: The study will help identify factors enabling the
      implementation of the HiAP approach at a municipal level, promoting the
      development of green spaces policies in urban areas in order to tackle the social
      inequities in health.

PMID- 29047363
TI  - Thymosin beta4 alleviates renal fibrosis and tubular cell apoptosis through TGF
      beta pathway inhibition in UUO rat models.
AB  - BACKGROUND: Thymosin beta4 (Tbeta4) is closely associated with the cytoskeleton,
      inflammation, wound healing, angiogenesis, apoptosis, and myocardial
      regeneration, but the effects of Tbeta4 treatment on chronic renal tubular
      interstitial fibrosis (CRTIF) are poorly known. This study aimed to examine the
      effects of Tbeta4 on the renal apoptosis and the expression of transforming
      growth factor (TGF-beta), E-cadherin, and alpha-smooth muscle actin (alpha-SMA)
      in CRTIF rat models. METHODS: Male SD rats were randomized into four groups (sham
      group, unilateral ureteral obstruction (UUO) group, UUO + low-dose Tbeta4 group,
      and UUO + high-dose Tbeta4 group). The pathological changes of kidney tissue and
      its function were assessed two weeks after UUO. In renal interstitial tissue,TGF
      beta, E-cadherin and alpha-SMA expression was detected by western blot. In
      tubular epithelial cells, E-cadherin and alpha-SMA expression was detected using
      Real-time qPCR and western blot. Cell apoptosis of rat renal interstitial tissue
      and tubular epithelial cells was evaluated by immunofluorescence and western
      blot. RESULTS: Two weeks after UUO, no differences in blood urea nitrogen and
      creatinine were observed between the four groups (P > 0.05). Compared to the UUO
      group, Tbeta4 treatment decreased the 24-h proteinuria (P < 0.001) and reduced
      the area of pathological change (P < 0.01); this effect was more apparent in the
      UUO + high-dose Tbeta4 group. Compared to the UUO group, a significant decrease
      in TGF-beta and alpha-SMA protein expression was observed in the high-dose Tbeta4
      group. The level of E-cadherin protein was lower in the UUO group than the Tbeta4
      groups, and high-dose Tbeta4 treatment further increased E-cadherin expression
      and improved cell apoptosis in the renal interstitial tissue. Analysis of in
      vitro tubular epithelial cells showed that alpha-SMA mRNA and protein expression
      decreased, while E-cadherin mRNA and protein expression increased by Tbeta4
      treatment. Similarly, these changes were more significant in the UUO + high-dose
      Tbeta4 group. Tbeta4 treatment improved the apoptosis of In vitro tubular
      epithelial cells compared with pure TGF-beta stimulation, and equally, the
      decrease of apoptosis was more apparent in the TGF-beta + high-dose Tbeta4 group.
      CONCLUSIONS: Tbeta4 treatment might alleviate the renal fibrosis and apoptosis of
      tubular epithelial cells through TGF-beta pathway inhibition in UUO rats with
      CRTIF.

PMID- 29047364
TI  - Mapping child maltreatment risk: a 12-year spatio-temporal analysis of
      neighborhood influences.
AB  - BACKGROUND: 'Place' matters in understanding prevalence variations and
      inequalities in child maltreatment risk. However, most studies examining
      ecological variations in child maltreatment risk fail to take into account the
      implications of the spatial and temporal dimensions of neighborhoods. In this
      study, we conduct a high-resolution small-area study to analyze the influence of
      neighborhood characteristics on the spatio-temporal epidemiology of child
      maltreatment risk. METHODS: We conducted a 12-year (2004-2015) small-area
      Bayesian spatio-temporal epidemiological study with all families with child
      maltreatment protection measures in the city of Valencia, Spain. As neighborhood
      units, we used 552 census block groups. Cases were geocoded using the family
      address. Neighborhood-level characteristics analyzed included three indicators of
      neighborhood disadvantage-neighborhood economic status, neighborhood education
      level, and levels of policing activity-, immigrant concentration, and residential
      instability. Bayesian spatio-temporal modelling and disease mapping methods were
      used to provide area-specific risk estimations. RESULTS: Results from a spatio
      temporal autoregressive model showed that neighborhoods with low levels of
      economic and educational status, with high levels of policing activity, and high
      immigrant concentration had higher levels of substantiated child maltreatment
      risk. Disease mapping methods were used to analyze areas of excess risk. Results
      showed chronic spatial patterns of high child maltreatment risk during the years
      analyzed, as well as stability over time in areas of low risk. Areas with
      increased or decreased child maltreatment risk over the years were also observed.
      CONCLUSIONS: A spatio-temporal epidemiological approach to study the geographical
      patterns, trends over time, and the contextual determinants of child maltreatment
      risk can provide a useful method to inform policy and action. This method can
      offer a more accurate description of the problem, and help to inform more
      localized prevention and intervention strategies. This new approach can also
      contribute to an improved epidemiological surveillance system to detect
      ecological variations in risk, and to assess the effectiveness of the initiatives
      to reduce this risk.

PMID- 29047365
TI  - The weight of work: the association between maternal employment and overweight in
      low- and middle-income countries.
AB  - BACKGROUND: Maternal employment has increased in low-and middle-income countries
      (LMIC) and is a hypothesized risk factor for maternal overweight due to increased
      income and behavioral changes related to time allocation. However, few studies
      have investigated this relationship in LMIC. METHODS: Using cross-sectional
      samples from Demographic and Health Surveys, we investigated the association
      between maternal employment and overweight (body mass index [BMI] >= 25 kg/m2)
      among women in 38 LMIC (N = 162,768). We categorized mothers as formally
      employed, informally employed, or non-employed based on 4 indicators: employment
      status in the last 12 months; aggregate occupation category (skilled, unskilled);
      type of earnings (cash only, cash and in-kind, in-kind only, unpaid); and
      seasonality of employment (all year, seasonal/occasional employment). Formally
      employed women were largely employed year-round in skilled occupations and earned
      a wage (e.g. professional), whereas informally employed women were often
      irregularly employed in unskilled occupations and in some cases, were paid in
      kind (e.g. domestic work). For within-country analyses, we used adjusted logistic
      regression models and included an interaction term to assess heterogeneity in the
      association by maternal education level. We then used meta-analysis and meta
      regression to explore differences in the associations pooled across countries.
      RESULTS: Compared to non-employed mothers, formally employed mothers had higher
      odds of overweight (pooled odds ratio [POR] = 1.3; 95% Confidence Interval [CI]
      1.2, 1.4) whereas informally employed mothers, compared to non-employed mothers,
      had lower odds of overweight (POR = 0.72; 95% CI: 0.64, 0.81). In 14 LMIC, the
      association varied by education. In these countries, the magnitude of the formal
      employment-overweight association was larger for women with low education (POR =
      1.5; 95% CI: 1.1, 1.9) compared to those with high education (POR = 1.2; 95% CI:
      1.0, 1.3). CONCLUSIONS: Formally employed mothers in LMIC have higher odds of
      overweight and the association varies by educational attainment in 14 countries.
      This knowledge highlights the importance of workplace initiatives to reduce the
      risk of overweight among working women in LMIC.

PMID- 29047366
TI  - The use of cinacalcet hinders the diagnosis of parathyroid carcinoma in a chronic
      dialysis patient: a case report.
AB  - BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in
      patients receiving chronic dialysis therapy. Although cinacalcet can control
      parathyroid function and bone turnover, preventing ectopic calcification remains
      challenging. Cinacalcet can also suppress PTH secretion due to parathyroid
      carcinoma in the same way as it does for parathyroid hyperplasia in the uremic
      condition. We present a case of parathyroid carcinoma partially controlled by
      cinacalcet, in which tumorous calcinosis was successfully resolved by total
      parathyroidectomy. CASE PRESENTATION: A female patient in her forties who had
      received dialysis for 12 years was referred to our hospital for painful ectopic
      calcifications on her right hip joint and both knees. Although she had been
      treated with alfacalcidol and cinacalcet for 2 years, this therapy had been
      discontinued 6 months earlier as a result of hypercalcemia. The patient exhibited
      normocalcemia (2.37 mmol/L) and hyperphosphatemia (2.42 mmol/L) with elevated
      intact parathyroid hormone (707,000 MUg/L). Ultrasonography revealed an enlarged
      parathyroid gland on the left lower side of the thyroid gland. The
      otolaryngologist surgeons had to perform an en bloc excision to remove this
      parathyroid gland because of tight adhesions. Histological examination revealed
      that parathyroid cells had invaded the surrounding skeletal muscle through
      fibrous capsules, consistent with parathyroid carcinoma. Her joint pain
      disappeared 2 weeks after parathyroidectomy, and the tumorous calcinosis had
      largely resolved after 1 year. CONCLUSIONS: Parathyroid carcinoma is a rare cause
      of hyperparathyroidism in end-stage kidney disease. Our case indicates that the
      use of cinacalcet hinders the diagnosis of parathyroid carcinoma in a chronic
      dialysis patient. When uncontrolled hypercalcemia and/or hyperphosphathemia
      develop during cinacalcet administration, parathyroidectomy should be considered
      to prevent a vicious exacerbation of ectopic calcification.

PMID- 29047367
TI  - Effectiveness and safety of beta blockers in the management of hypertension in
      older adults: a systematic review to help reduce inappropriate prescribing.
AB  - BACKGROUND: The benefit from a blood pressure lowering therapy with beta blockers
      may not outweigh its risks, especially in older populations. The aim of this
      study was to look for evidence on risks and benefits of beta blockers in older
      adults and to use this evidence to develop recommendations for the electronic
      decision support tool of the PRIMA-eDS project. METHODS: Systematic review of the
      literature using a stage approach with searches for systematic reviews and meta
      analyses first, and individual studies only if the previous searches are
      inconclusive. The target population were older adults (>=65 years old) with
      hypertension. We included studies reporting on the effectiveness and/or safety of
      beta blockers on clinically relevant endpoints (e.g. mortality, cardiovascular
      events, and stroke) in the management of hypertension. The recommendations were
      developed according to the GRADE methodology. RESULTS: Fifteen studies were
      included, comprising one meta-analysis, four randomized controlled trials, six
      secondary analyses of randomized controlled trials and four observational
      studies. Seven studies involved only older adults and eight studies reported
      subgroup analyses by age. With regard to a composite endpoint (death, stroke or
      myocardial infarction) beta blockers were associated with a higher risk of events
      then were other antihypertensive agents. Further, beta blockers showed no benefit
      compared to other antihypertensive agents or placebo regarding mortality. They
      appear to be less effective than other antihypertensive agents in reducing
      cardiovascular events. Contradictory results were found regarding the effect of
      beta blockers on stroke. None of the studies explored the effect on quality of
      life, hospitalisation, functional impairment/status, safety endpoints or renal
      failure. CONCLUSION: The quality of current evidence to interpret the benefits of
      beta blockers in hypertension is rather weak. It cannot be recommended to use
      beta blockers in older adults as first line agent for hypertension.

PMID- 29047368
TI  - Comparison and predictors of treatment adherence and remission among patients
      with schizophrenia treated with paliperidone palmitate or atypical oral
      antipsychotics in community behavioral health organizations.
AB  - BACKGROUND: Nonadherence to antipsychotic treatment increases the likelihood of
      relapse and progressive symptomatology in patients with schizophrenia. Atypical
      long-acting injectables, including paliperidone palmitate (PP), may increase
      adherence and improve symptoms. This study compared and assessed predictors of
      treatment patterns and symptom remission among schizophrenia patients treated
      with PP versus atypical oral antipsychotic therapy (OAT) in community behavioral
      health organizations (CBHOs). METHODS: This retrospective cohort analysis
      evaluated 763 patients with schizophrenia and new (PP-N; N = 174) or continuing
      (PP-C; N = 308) users of PP, or new users of OAT (N = 281) at enrollment in the
      REACH-OUT study (2010-2013). Treatment outcomes assessed at 1 year were
      discontinuation, and adherence, measured by proportion of days covered (PDC) or
      medication possession ratio (MPR). Remission status was assessed using the
      Structured Clinical Interview for Symptoms of Remission (SCI-SR). A machine
      learning platform, Reverse Engineering and Forward Simulation (REFSTM), was used
      to identify predictors of study outcomes. Multivariate Cox and generalized linear
      regressions estimated the adjusted hazard ratios (HRs) or odds ratios (ORs) with
      95% confidence intervals. RESULTS: Among PP-N users, 27% discontinued their
      initial treatment regimen versus 51% (p < 0.001) of OAT users. PP-N (vs OAT; HR =
      0.49 [0.31-0.76]) users and males (HR = 0.65 [0.46-0.92]) had significantly lower
      rates of discontinuation. Relative to OAT, PP-N had a 36% [31%-42%] higher MPR
      and a 10-fold increased achievement of PDC >=80% (OR = 10.46 [5.72-19.76]). PP
      users were significantly more likely to achieve remission in follow-up (PP-N vs
      OAT: OR = 2.65 [1.39-5.05]; PP-C vs OAT: OR = 1.83 [1.03-3.25]). CONCLUSIONS:
      Relative to OAT, PP was associated with improved adherence, less frequent
      treatment discontinuation, and improved symptom remission in this CBHO study
      population.

PMID- 29047369
TI  - Intrasession repeatability of ocular anatomical measurements obtained with a
      multidiagnostic device in healthy eyes.
AB  - BACKGROUND: To evaluate the intrasession repeatability of anterior chamber depth
      (ACD), central (CCT) and peripheral corneal thickness (PCT), white-to-white
      diameter (WTW), and irido-corneal angle (IA) measurements obtained with a
      multidiagnostic device in healthy eyes. METHODS: A total of 107 eyes of 107
      patients ranging in age from 23 to 65 years were examined with the VX120 system
      (Visionix-Luneau Technologies). Three consecutive measurements were obtained with
      this device to assess the intrasession repeatability of ACD, CCT, PCT at
      different nasal and temporal locations, WTW, and nasal and temporal IA. Data
      analysis included the calculation of within-subject standard deviation (Sw),
      intrasubject precision (1.96xSw), coefficient of variation (CV) and intraclass
      correlation coefficient (ICC). RESULTS: The Sw and CV for ACD was 0.03 mm and
      1.16%, respectively, with an ICC of 0.992. The Sw values for central and
      peripheral pachymetric measurements were below 9 MUm, with CV of less than 1.6%
      and ICC of 0.976 or higher. For IA measurements, Sw values of 0.84 or lower were
      found, with a CV between 1 and 2%, and an ICC of more than 0.970. The Sw for WTW
      was 0.24 mm and the CV was 1.95%. No statistically significant correlations were
      found between any anatomical parameter evaluated and their Sw and CV values
      associated (-0.220 <= r <= 0.204, p >= 0.125). CONCLUSIONS: The VX120 system is
      able to provide repeatable measurements of anatomical parameters in healthy eyes.
      Inter-observer repeatability should be evaluated in future studies.

PMID- 29047370
TI  - The recent development and applications of fluidic channels by 3D printing.
AB  - The technology of "Lab-on-a-Chip" allows the synthesis and analysis of chemicals
      and biological substance within a portable or handheld device. The 3D printed
      structures enable precise control of various geometries. The combination of these
      two technologies in recent years makes a significant progress. The current
      approaches of 3D printing, such as stereolithography, polyjet, and fused
      deposition modeling, are introduced. Their manufacture specifications, such as
      surface roughness, resolution, replication fidelity, cost, and fabrication time,
      are compared with each other. Finally, novel application of 3D printed channel in
      biology are reviewed, including pathogenic bacteria detection using magnetic
      nanoparticle clusters in a helical microchannel, cell stimulation by 3D chemical
      gradients, perfused functional vascular channels, 3D tissue construct, organ-on-a
      chip, and miniaturized fluidic "reactionware" devices for chemical syntheses.
      Overall, the 3D printed fluidic chip is becoming a powerful tool in the both
      medical and chemical industries.

PMID- 29047371
TI  - Needle acquisition patterns, network risk and social capital among rural PWID in
      Puerto Rico.
AB  - BACKGROUND: People who inject drugs (PWID) take on significant risks of
      contracting blood-borne infection, including injecting with a large number of
      partners and acquiring needles from unsafe sources. When combined, risk of
      infection can be magnified. METHODS: Using a sample of PWID in rural Puerto Rico,
      we model the relationship between a subject's number of injection partners and
      the likelihood of having used an unsafe source of injection syringes. Data
      collection with 315 current injectors identified six sources of needles. RESULTS:
      Of the six possible sources, only acquisition from a seller (paid or free), or
      using syringes found on the street, was significantly related to number of
      partners. CONCLUSIONS: These results suggest that sources of syringes do serve to
      multiply risk of infection caused by multi-partner injection concurrency. They
      also suggest that prior research on distinct forms of social capital among PWID
      may need to be rethought.

PMID- 29047372
TI  - Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management
      of type 2 diabetes in older adults: a systematic review and development of
      recommendations to reduce inappropriate prescribing.
AB  - BACKGROUND: Preventable drug-related hospital admissions can be associated with
      drugs used in diabetes and the benefits of strict diabetes control may not
      outweigh the risks, especially in older populations. The aim of this study was to
      look for evidence on risks and benefits of DPP-4 inhibitors in older adults and
      to use this evidence to develop recommendations for the electronic decision
      support tool of the PRIMA-eDS project. METHODS: Systematic review using a staged
      approach which searches for systematic reviews and meta-analyses first, then
      individual studies only if prior searches were inconclusive. The target
      population were older people (>=65 years old) with type 2 diabetes. We included
      studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the
      management of type 2 diabetes. Studies were included irrespective of DPP-4
      inhibitors prescribed as monotherapy or in combination with any other drug for
      the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors
      compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non
      pharmacological intervention. RESULTS: Thirty studies (reported in 33
      publications) were included: 1 meta-analysis, 17 intervention studies and 12
      observational studies. Sixteen studies were focused on older adults and 14
      studies reported subgroup analyses in participants >=65, >=70, or >=75 years.
      Comorbidities were reported by 26 studies and frailty or functional status by one
      study. There were conflicting findings regarding the effectiveness of DPP-4
      inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better
      safety than placebo and other antidiabetic drugs. However, these safety data are
      mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c
      control levels recommended for younger people. One recommendation was developed
      advising clinicians to reconsider the use of DPP-4 inhibitors for the management
      of type 2 diabetes in older adults with HbA1c <8.5% because of scarce data on
      clinically relevant benefits of their use. Twenty-two of the included studies
      were funded by pharmaceutical companies and authored or co-authored by employees
      of the sponsor. CONCLUSIONS: Other than the surrogate endpoint of improved
      glycaemic control, data on clinically relevant benefits of DPP-4 inhibitors in
      the treatment of type 2 diabetes mellitus in older adults is scarce. DPP-4
      inhibitors might have a lower risk of hypoglycaemia compared to other
      antidiabetic drugs but data show conflicting findings for long-term benefits.
      Further studies are needed that evaluate the risks and benefits of DPP-4
      inhibitors for the management of type 2 diabetes mellitus in older adults, using
      clinically relevant outcomes and including representative samples of older adults
      with information on their frailty status and comorbidities. Studies are also
      needed that are independent of pharmaceutical company involvement.

PMID- 29047373
TI  - Correction to: A large and persistent outbreak of typhoid fever caused by
      consuming contaminated water and street-vended beverages: Kampala, Uganda,
      January - June 2015.

PMID- 29047374
TI  - Ideal cardiovascular health and the subclinical impairments of cardiovascular
      diseases: a cross-sectional study in central south China.
AB  - BACKGROUND: Ideal cardiovascular health (CVH) is related to a low cardiovascular
      disease risk profile. This study aimed to investigate CVH metrics with both the
      biomarkers and markers of subclinical impairments of cardiovascular diseases
      (CVDs) in subjects from central south China. METHODS: The ideal CVH score (non
      smoking status; ideal body mass index; regular physical activity; healthy diet;
      and an optimal serum cholesterol, blood pressure, and glucose profile; 1 point
      for each; total score: 0-7) was collected from 3009 participants without a
      history of CVDs. Subclinical biomarkers were assessed using C-reactive protein,
      homocysteine, and microalbuminuria. The presence of subclinical disease markers
      was defined as having at least one of the following: increased carotid intima
      media thickness, carotid plaque, left ventricular hypertrophy, left ventricular
      systolic dysfunction, or a reduced ankle-brachial index. The association of
      biomarkers and markers with the CVH score was evaluated using multivariate
      logistic regression and linear regression analyses. RESULTS: Only 0.2% of the
      study participants met all 7 ideal CVH metrics (CVH score = 7). Compared to the
      female participants, the male participants had poorer CVH profiles and a higher
      incidence of subclinical lesions (P < 0.05). In the fully adjusted models, per 1
      unit increase in the CVH score was inversely associated with the biomarker levels
      (beta = -0.092 - -0.224, P < 0.05 for all) and the odds of the presence of
      markers (odds ratio, 0.808; 95% confidence interval, 0.755-0.865). Similar
      relationships were observed in the gender subgroups and were stronger in the
      females. CONCLUSION: A clear inverse association was observed between the
      biomarkers or markers of subclinical impairments and the CVH score in a central
      south Chinese population, implying the importance of ideal CVH for the primordial
      prevention of CVDs.

PMID- 29047375
TI  - A low initial serum sodium level is associated with an increased risk of
      overcorrection in patients with chronic profound hyponatremia: a retrospective
      cohort analysis.
AB  - BACKGROUND: Even with abundant evidence for osmotic demyelination in patients
      with hyponatremia, the risk factors for overcorrection have not been fully
      investigated. Therefore the purpose of this study is to clarify the risks for
      overcorrection during the treatment of chronic profound hyponatremia. METHODS:
      This is a single-center retrospective observational study. We enrolled 56 adult
      patients with a serum sodium (SNa) concentration of <=125 mEq/L who were treated
      in an intensive care unit by nephrologists using a locally developed, fixed
      treatment algorithm between February 2012 and April 2014. The impact of patient
      parameters on the incidence of overcorrection was estimated using univariable and
      multivariable logistic regression models. Overcorrection was defined as an
      increase of SNa by >10 mEq/L and >18 mEq/L during the first 24 and 48 h,
      respectively. RESULTS: The median age was 78 years, 48.2% were male, and 94.6% of
      the patients presented with symptoms associated with hyponatremia. The initial
      median SNa was 115 mEq/L (quartile, 111-119 mEq/L). A total of 11 (19.6%)
      patients met the criteria for overcorrection with 9 (16.0%) occurring at 24 h, 6
      (10.7%) at 48 h, and 4 (7.1%) at both 24 and 48 h. However, none of these
      patients developed osmotic demyelination. Primary polydipsia, initial SNa, and
      early urine output were the significant risk factors for overcorrection on
      univariable analysis. Multivariable analysis revealed that the initial SNa had a
      statistically significant impact on the incidence of overcorrection with an
      adjusted odds ratio of 0.84 (95% confidence interval, 0.70-0.98; p = 0.037) for
      every 1 mEq/L increase. Additionaly, the increase in SNa during the first 4 h and
      early urine output were significantly higher in patients with overcorrection than
      in those without (p = 0.001 and 0.005, respectively). CONCLUSIONS: An initial low
      level of SNa was associated with an increased risk of overcorrection in patients
      with profound hyponatremia. In this regard, the rapid increase in SNa during the
      first 4 h may play an important role.

PMID- 29047376
TI  - Women's education level amplifies the effects of a livelihoods-based intervention
      on household wealth, child diet, and child growth in rural Nepal.
AB  - BACKGROUND: Many organizations seek to alleviate poverty in the developing world,
      often focusing their interventions on women. The role, status, and education of
      women are fundamentally important facets of development. Thus, understanding the
      interaction of women's educational level and the response to interventions is
      important. Therefore, we examined the impact of educational level of household
      adults on responses to a livestock-based community intervention. METHODS: Six
      pair-matched communities in 3 districts of Nepal (Chitwan/Nawalparasi/Nuwakot),
      were randomly assigned to receive community development activities via women's
      self-help groups at baseline or 1 year later. At 6 intervals over 48 months, a
      125- item questionnaire addressing family demographics and child health/nutrition
      was completed in each household, plus child growth monitoring. Results were
      analyzed in relation to the highest education attained by any woman in the
      household, the child's mother, men, or any other adult in the household. RESULTS:
      Outcomes (wealth, water/toilet availability, child diet diversity and growth) all
      significantly related to adult education. However, notable differences were found
      comparing the impact of men's and women's education. Percent change in wealth
      score was significant only in households where women had primary or secondary
      education (respectively, p = .0009 and p < .0001). Increased soap use related
      only to women's education (p < .0001). When adjusted for group assignment,
      baseline income, wealth, and animal scores, higher women's education was
      significantly associated with increased household wealth (p < .0001), better
      child height-for-age z scores (HAZ, p = .005), and improved child diet diversity
      (p = .01). Higher mother's education predicted better child HAZ (primary, p =
      .01, secondary, p = .03) and diet diversity (primary, p = .05, secondary, p <
      .0001). Higher men's education was significantly associated with household wealth
      (p = .02) and child diet diversity (p = .04), but not HAZ; higher education of
      any household member was associated only with household wealth (p < .0001).
      Moreover, households where the mother's education was better than the best
      educated man also were significantly more likely to have children with better HAZ
      and dietary diversity (p = .03, p < .0001). Thus, the educational level of women
      and mothers had the broadest impact on child outcome variables. CONCLUSIONS:
      Household characteristics vary among participants in most community development
      projects. Of these, adult education likely mediates response to the inputs
      provided by the intervention. Particularly in interventions directed towards
      women, better education may enhance the ability of households to put
      interventions into practice, thus improving wealth, hygiene, and child diet and
      growth indices.

PMID- 29047377
TI  - Cognitive impairment profile in adult patients with Niemann pick type C disease.
AB  - BACKGROUND: Cognitive impairment is one of the core symptoms of Niemann Pick type
      C (NPC) disease, but few data concerning the neuropsychological profile of NPC
      patients are available. The aim of our study was to characterize cognitive
      impairments in NPC disease and to assess the evolution of these symptoms and the
      impact of miglustat on cognitive follow-up. METHODS: We conducted a retrospective
      study of 21 adult patients diagnosed with NPC disease. Neuropsychological data
      (global cognitive efficiency, language, attention, executive functions, praxis,
      and visuoconstructive functions tests) were retrieved to describe the cognitive
      profile of patients. Cognitive impairment scores over time were assessed under
      treatment by miglustat. RESULTS: The majority of patients (90%) were impaired in
      one or more cognitive function. Executive functions and attention were the most
      impaired cognitive functions. Conversely, storage in the episodic memory was
      preserved in 61.5% of cases. Mean neuropsychological scores were stable during
      the period under miglustat (mean of 3.8 years). CONCLUSIONS: This study is one of
      the first to assess the cognitive profile of adult NPC patients. This profile is
      not specific to attention and executive dysfunctions; however, the preservation
      of storage in the episodic memory is promising for cognitive remediation. Further
      studies are needed to confirm the role of miglustat on cognition, but in this
      study, patients were stable under this treatment.

PMID- 29047378
TI  - Comparison of strain parameters in dyssynchronous heart failure between speckle
      tracking echocardiography vendor systems.
AB  - BACKGROUND: Although mechanical dyssynchrony parameters derived by speckle
      tracking echocardiography (STE) may predict response to cardiac resynchronization
      therapy (CRT), comparability of parameters derived with different STE vendors is
      unknown. METHODS: In the MARC study, echocardiographic images of heart failure
      patients obtained before CRT implantation were prospectively analysed with vendor
      specific STE software (GE EchoPac and Philips QLAB) and vendor-independent
      software (TomTec 2DCPA). Response was defined as change in left ventricular (LV)
      end-systolic volume between examination before and six-months after CRT
      implantation. Basic longitudinal strain and mechanical dyssynchrony parameters
      (septal to lateral wall delay (SL-delay), septal systolic rebound stretch
      (SRSsept), and systolic stretch index (SSI)) were obtained from either separate
      septal and lateral walls, or total LV apical four chamber. Septal strain patterns
      were categorized in three types. The coefficient of variation and intra-class
      correlation coefficient (ICC) were analysed. Dyssynchrony parameters were
      associated with CRT response using univariate regression analysis and C
      statistics. RESULTS: Two-hundred eleven patients were analysed. GE-cohort (n =
      123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177
      ms (IQR: 160-192), LV ejection fraction: 26 +/- 7%. Philips-cohort (n = 88): age
      67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection
      fraction: 27 +/- 8. LV derived peak strain was comparable in the GE- (GE: -7.3 +/
      3.1%, TomTec: -6.4 +/- 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 +/-
      2.7%, TomTec: -7.7 +/- 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs.
      TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were
      higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs.
      QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was
      low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal
      strain patterns, SRSsept and SSI were associated with changes in LV end-systolic
      volume for all vendors. SRSsept and SSI had relative varying C-statistic values
      (range: 0.530-0.705) and different cut-off values between vendors. CONCLUSIONS:
      Although global longitudinal strain analysis showed fair comparability,
      assessment of dyssynchrony parameters was vendor specific and not applicable
      outside the context of the implemented platform. While the standardization
      taskforce took an important step for global peak strain, further standardization
      of STE is still warranted.

PMID- 29047379
TI  - Physicians' attitude towards selection of second line therapy with nilotinib and
      dasatinib in chronic myeloid leukemia patients.
AB  - We investigated factors that physicians consider of most importance in the
      selection of second line tyrosine kinase inhibitors treatments (TKIs) in chronic
      myeloid leukemia patients (CML).

PMID- 29047380
TI  - Population genetics of Enterocytozoon bieneusi in captive giant pandas of China.
AB  - BACKGROUND: Most studies on Enterocytozoon bieneusi are conducted based on the
      internal transcribed spacer (ITS) region of the rRNA gene, whereas some have
      examined E. bieneusi population structures. Currently, the population genetics of
      this pathogen in giant panda remains unknown. The objective of this study was to
      determine the E. bieneusi population in captive giant pandas in China. RESULTS:
      We examined 69 E. bieneusi-positive specimens from captive giant pandas in China
      using five loci (ITS, MS1, MS3, MS4 and MS7) to infer E. bieneusi population
      genetics. For multilocus genotype (MLG) analysis of E. bieneusi-positive
      isolates, the MS1, MS3, MS4, and MS7 microsatellite and minisatellite loci were
      amplified and sequenced in 48, 45, 50 and 47 specimens, respectively, generating
      ten, eight, nine and five types. We successfully amplified 36 specimens and
      sequenced all five loci, forming 24 MLGs. Multilocus sequence analysis revealed a
      strong and significant linkage disequilibrium (LD), indicating a clonal
      population. This result was further supported by measurements of pairwise
      intergenic LD and a standardized index of association (I SA) from allelic profile
      data. The analysis in STRUCTURE suggested three subpopulations in E. bieneusi,
      further confirmed using right's fixation index (F ST). Subpopulations 1 and 2
      exhibited an epidemic structure, whereas subpopulation 3 had a clonal structure.
      CONCLUSIONS: Our results describe E. bieneusi population genetics in giant pandas
      for the first time, improving the current understanding E. bieneusi epidemiology
      in the studied region. These data also benefit future studies exploring potential
      transmission risks from pandas to other animals, including humans.

PMID- 29047381
TI  - A critical appraisal of guidelines used for management of severe acute
      malnutrition in South Africa's referral system.
AB  - BACKGROUND: Focusing on healthcare referral processes for children with severe
      acute malnutrition (SAM) in South Africa, this paper discusses the
      comprehensiveness of documents (global and national) that guide the country's SAM
      healthcare. This research is relevant because South African studies on SAM mostly
      examine the implementation of WHO guidelines in hospitals, making their technical
      relevance to the country's lower level and referral healthcare system under
      explored. METHODS: To add to both literature and methods for studying SAM
      healthcare, we critically appraised four child healthcare guidelines (global and
      national) and conducted complementary expert interviews (n = 5). Combining both
      methods enabled us to examine the comprehensiveness of the documents as related
      to guiding SAM healthcare within the country's referral system as well as the
      credibility (rigour and stakeholder representation) of the guideline documents'
      development process. RESULTS: None of the guidelines appraised covered all steps
      of SAM referrals; however, each addressed certain steps thoroughly, apart from
      transit care. Our study also revealed that national documents were mostly
      modelled after WHO guidelines but were not explicitly adapted to local context.
      Furthermore, we found most guidelines' formulation processes to be unclear and
      stakeholder involvement in the process to be minimal. CONCLUSION: In adapting
      guidelines for management of SAM in South Africa, it is important that local
      context applicability is taken into consideration. In doing this, wider
      stakeholder involvement is essential; this is important because factors that
      affect SAM management go beyond in-hospital care. Community, civil society,
      medical and administrative involvement during guideline formulation processes
      will enhance acceptability and adherence to the guidelines.

PMID- 29047382
TI  - A novel and fully automated mammographic texture analysis for risk prediction:
      results from two case-control studies.
AB  - BACKGROUND: The percentage of mammographic dense tissue (PD) is an important risk
      factor for breast cancer, and there is some evidence that texture features may
      further improve predictive ability. However, relatively little work has assessed
      or validated textural feature algorithms using raw full field digital mammograms
      (FFDM). METHOD: A case-control study nested within a screening cohort (age 46-73
      years) from Manchester UK was used to develop a texture feature risk score (264
      cases diagnosed at the same time as mammogram of the contralateral breast, 787
      controls) using the least absolute shrinkage and selection operator (LASSO)
      method for 112 features, and validated in a second case-control study from the
      same cohort but with cases diagnosed after the index mammogram (317 cases, 931
      controls). Predictive ability was assessed using deviance and matched concordance
      index (mC). The ability to improve risk estimation beyond percent volumetric
      density (Volpara) was evaluated using conditional logistic regression. RESULTS:
      The strongest features identified in the training set were "sum average" based on
      the grey-level co-occurrence matrix at low image resolutions (original resolution
      10.628 pixels per mm; downsized by factors of 16, 32 and 64), which had a better
      deviance and mC than volumetric PD. In the validation study, the risk score
      combining the three sum average features achieved a better deviance than
      volumetric PD (Deltachi2 = 10.55 or 6.95 if logarithm PD) and a similar mC to
      volumetric PD (0.58 and 0.57, respectively). The risk score added independent
      information to volumetric PD (Deltachi2 = 14.38, p = 0.0008). CONCLUSION:
      Textural features based on digital mammograms improve risk assessment beyond
      volumetric percentage density. The features and risk score developed need further
      investigation in other settings.

PMID- 29047383
TI  - A novel small molecule inhibitor of p32 mitochondrial protein overexpressed in
      glioma.
AB  - BACKGROUND: The mitochondrial protein p32 is a validated therapeutic target of
      cancer overexpressed in glioma. Therapeutic targeting of p32 with monoclonal
      antibody or p32-binding LyP-1 tumor-homing peptide can limit tumor growth.
      However, these agents do not specifically target mitochondrial-localized p32 and
      would not readily cross the blood-brain barrier to target p32-overexpressing
      gliomas. Identifying small molecule inhibitors of p32 overexpressed in cancer is
      a more rational therapeutic strategy. Thus, in this study we employed a
      pharmacophore modeling strategy to identify small molecules that could bind and
      inhibit mitochondrial p32. METHODS: A pharmacophore model of C1q and LyP-1
      peptide association with p32 was used to screen a virtual compound library. A
      primary screening assay for inhibitors of p32 was developed to identify compounds
      that could rescue p32-dependent glutamine-addicted glioma cells from glutamine
      withdrawal. Inhibitors from this screen were analyzed for direct binding to p32
      by fluorescence polarization assay and protein thermal shift. Affect of the p32
      inhibitor on glioma cell proliferation was assessed by Alamar Blue assay, and
      affect on metabolism was examined by measuring lactate secretion. RESULTS:
      Identification of a hit compound (M36) validates the pharmacophore model. M36
      binds directly to p32 and inhibits LyP-1 tumor homing peptide association with
      p32 in vitro. M36 effectively inhibits the growth of p32 overexpressing glioma
      cells, and sensitizes the cells to glucose depletion. CONCLUSIONS: This study
      demonstrates a novel screening strategy to identify potential inhibitors of
      mitochondrial p32 protein overexpressed in glioma. High throughput screening
      employing this strategy has potential to identify highly selective, potent, brain
      penetrant small molecules amenable for further drug development.

PMID- 29047384
TI  - Enhancing evidence-based diabetes and chronic disease control among local health
      departments: a multi-phase dissemination study with a stepped-wedge cluster
      randomized trial component.
AB  - BACKGROUND: The rates of diabetes and prediabetes in the USA are growing,
      significantly impacting the quality and length of life of those diagnosed and
      financially burdening society. Premature death and disability can be prevented
      through implementation of evidence-based programs and policies (EBPPs). Local
      health departments (LHDs) are uniquely positioned to implement diabetes control
      EBPPs because of their knowledge of, and focus on, community-level needs,
      contexts, and resources. There is a significant gap, however, between known
      diabetes control EBPPs and actual diabetes control activities conducted by LHDs.
      The purpose of this study is to determine how best to support the use of evidence
      based public health for diabetes (and related chronic diseases) control among
      local-level public health practitioners. METHODS/DESIGN: This paper describes the
      methods for a two-phase study with a stepped-wedge cluster randomized trial that
      will evaluate dissemination strategies to increase the uptake of public health
      knowledge and EBPPs for diabetes control among LHDs. Phase 1 includes development
      of measures to assess practitioner views on and organizational supports for
      evidence-based public health, data collection using a national online survey of
      LHD chronic disease practitioners, and a needs assessment of factors influencing
      the uptake of diabetes control EBPPs among LHDs within one state in the USA.
      Phase 2 involves conducting a stepped-wedge cluster randomized trial to assess
      effectiveness of dissemination strategies with local-level practitioners at LHDs
      to enhance capacity and organizational support for evidence-based diabetes
      prevention and control. Twelve LHDs will be selected and randomly assigned to one
      of the three groups that cross over from usual practice to receive the
      intervention (dissemination) strategies at 8-month intervals; the intervention
      duration for groups ranges from 8 to 24 months. Intervention (dissemination)
      strategies may include multi-day in-person workshops, electronic information
      exchange methods, technical assistance through a knowledge broker, and
      organizational changes to support evidence-based public health approaches.
      Evaluation methods comprise surveys at baseline and the three crossover time
      points, abstraction of local-level diabetes and chronic disease control program
      plans and progress reports, and social network analysis to understand the
      relationships and contextual issues that influence EBPP adoption. TRIAL
      REGISTRATION: ClinicalTrial.gov, NCT03211832.

PMID- 29047385
TI  - Fully quantitative cardiovascular magnetic resonance myocardial perfusion ready
      for clinical use: a comparison between cardiovascular magnetic resonance imaging
      and positron emission tomography.
AB  - BACKGROUND: Recent studies have shown that quantification of myocardial perfusion
      (MP) at stress and myocardial perfusion reserve (MPR) offer additional diagnostic
      and prognostic information compared to qualitative and semi-quantitative
      assessment of myocardial perfusion distribution in patients with coronary artery
      disease (CAD). Technical advancements have enabled fully automatic quantification
      of MP using cardiovascular magnetic resonance (CMR) to be performed in-line in a
      clinical workflow. The aim of this study was to validate the use of the automated
      CMR perfusion mapping technique for quantification of MP using 13N-NH3 cardiac
      positron emission tomography (PET) as the reference method. METHODS: Twenty-one
      patients with stable CAD were included in the study. All patients underwent
      adenosine stress and rest perfusion imaging with 13N-NH3 PET and a dual sequence,
      single contrast bolus CMR on the same day. Global and regional MP were quantified
      both at stress and rest using PET and CMR. RESULTS: There was good agreement
      between global MP quantified by PET and CMR both at stress (-0.1 +/- 0.5
      ml/min/g) and at rest (0 +/- 0.2 ml/min/g) with a strong correlation (r = 0.92, p
      < 0.001; y = 0.94* + 0.14). Furthermore, there was strong correlation between CMR
      and PET with regards to regional MP (r = 0.83, p < 0.001; y = 0.87* + 0.26) with
      a good agreement (-0.1 +/- 0.6 ml/min/g). There was also a significant
      correlation between CMR and PET with regard to global and regional MPR (r = 0.69,
      p = 0.001 and r = 0.57, p < 0.001, respectively). CONCLUSIONS: There is good
      agreement between MP quantified by 13N-NH3 PET and dual sequence, single contrast
      bolus CMR in patients with stable CAD. Thus, CMR is viable in clinical practice
      for quantification of MP.

PMID- 29047386
TI  - Epoetin beta pegol (continuous erythropoietin receptor activator, CERA) is
      another choice for the treatment of anemia in myelodysplastic syndrome: a case
      report.
AB  - BACKGROUND: In most patients, anemia is present when myelodysplastic syndrome is
      diagnosed. Although darbepoetin alpha is the first-choice supportive therapy for
      low-risk myelodysplastic syndrome, half of all patients develop a loss of
      response to darbepoetin alpha within 12 months. However, few reports have
      described supportive therapy after the loss of response to darbepoetin alpha.
      CASE PRESENTATION: We herein present a case involving a 65-year-old Japanese
      woman with low-risk myelodysplastic syndrome whose erythropoiesis-stimulating
      agent treatment was switched from darbepoetin alpha to epoetin beta pegol
      (continuous erythropoietin receptor activator) to treat transfusion-dependent
      anemia. The frequent transfusions required to treat the anemia resulted in
      transfusion-associated circulatory overload. The transfusion-dependent anemia was
      initially treated with darbepoetin alpha, which negated the requirement for
      transfusion. However, after 12 months of darbepoetin alpha therapy, the
      hemoglobin concentration sharply declined. We switched her therapy from
      darbepoetin alpha to continuous erythropoietin receptor activator to avoid
      transfusion. After initiation of continuous erythropoietin receptor activator
      therapy, the hemoglobin concentration gradually increased and transfusion was not
      required. At the time of writing, no progression of the anemia had occurred.
      CONCLUSIONS: Although darbepoetin alpha is the first-choice supportive therapy
      for low-risk myelodysplastic syndrome, continuous erythropoietin receptor
      activator might be considered the second-choice therapy.

PMID- 29047387
TI  - Isothermal diagnostic assays for the detection of soil-transmitted helminths
      based on the SmartAmp2 method.
AB  - BACKGROUND: Diagnosis of soil-transmitted helminths (STHs) has traditionally
      relied on stool microscopy, which has a number of critical deficiencies.
      Molecular diagnostics are powerful tools to identify closely related species, but
      the requirement for costly equipment makes their implementation difficult in low
      resource or field settings. Rapid, sensitive and cost-effective diagnostic tools
      are crucial for accurate estimation of STH infection intensity in MDA programmes
      in which the goal is to reduce morbidity following repeated rounds of
      chemotherapy. RESULTS: In this study, colourimetric isothermal assays were
      developed using SmartAmp2 primer sets and reagents in loop-mediated amplification
      (LAMP) assays. Species-specific primer sets, designed on a specific target
      sequence in the beta-tubulin gene, were used to identify Necator americanus,
      Trichuris trichiura and Ascaris lumbricoides. After initial optimization on
      control plasmids and genomic DNA from adult worms, assays were evaluated on field
      samples. Assays showed high sensitivity and demonstrated high tolerance to
      inhibitors in spiked faecal samples. Rapid and sensitive colourimetric assays
      were successfully developed to identify the STHs in field samples using hydroxy
      napthol blue (HNB) dye. CONCLUSIONS: Rapid and simple colourimetric diagnostic
      assays, using the SmartAmp2 method, were developed, with the potential to be
      applied in the field for detection of STH infections and the estimation of
      response to treatment. However, further validation on large numbers of field
      samples is needed.

PMID- 29047388
TI  - Challenges in implementing uncomplicated malaria treatment in children: a health
      facility survey in rural Malawi.
AB  - BACKGROUND: Prompt and effective malaria treatment are key in reducing
      transmission, disease severity and mortality. With the current scale-up of
      artemisinin-based combination therapy (ACT) coverage, there is need to focus on
      challenges affecting implementation of the intervention. Routine indicators focus
      on utilization and coverage, neglecting implementation quality. A health system
      in rural Malawi was assessed for uncomplicated malaria treatment implementation
      in children. METHODS: A cross-sectional health facility survey was conducted in
      six health centres around the Majete Wildlife Reserve in Chikwawa district using
      a health system effectiveness approach to assess uncomplicated malaria treatment
      implementation. Interviews with health facility personnel and exit interviews
      with guardians of 120 children under 5 years were conducted. RESULTS: Health
      workers appropriately prescribed an ACT and did not prescribe an ACT to 73% (95%
      CI 63-84%) of malaria rapid diagnostic test (RDT) positive and 98% (95% CI 96
      100%) RDT negative children, respectively. However, 24% (95% CI 13-37%) of
      children receiving artemisinin-lumefantrine had an inappropriate dose by weight.
      Health facility findings included inadequate number of personnel (average: 2.1
      health workers per 10,000 population), anti-malarial drug stock-outs or not
      supplied, and inconsistent health information records. Guardians of 59% (95% CI
      51-69%) of children presented within 24 h of onset of child's symptoms.
      CONCLUSION: The survey presents an approach for assessing treatment
      effectiveness, highlighting bottlenecks which coverage indicators are incapable
      of detecting, and which may reduce quality and effectiveness of malaria
      treatment. Health service provider practices in prescribing and dosing anti
      malarial drugs, due to drug stock-outs or high patient load, risk development of
      drug resistance, treatment failure and exposure to adverse effects.

PMID- 29047389
TI  - Investigating local policy drivers for alcohol harm prevention: a comparative
      case study of two local authorities in England.
AB  - BACKGROUND: The considerable challenges associated with implementing national
      level alcohol policies have encouraged a renewed focus on the prospects for local
      level policies in the UK and elsewhere. We adopted a case study approach to
      identify the major characteristics and drivers of differences in the patterns of
      local alcohol policies and services in two contrasting local authority (LA) areas
      in England. METHODS: Data were collected via thirteen semi-structured interviews
      with key informants (including public health, licensing and trading standards)
      and documentary analysis, including harm reduction strategies and statements of
      licensing policy. A two-stage thematic analysis was used to categorize all
      relevant statements into seven over-arching themes, by which document sources
      were then also analysed. RESULTS: Three of the seven over-arching themes (drink
      environment, treatment services and barriers and facilitators), provided for the
      most explanatory detail informing the contrasting policy responses of the two
      LAs: LA1 pursued a risk-informed strategy via a specialist police team working
      proactively with problem premises and screening systematically to identify
      riskier drinking. LA2 adopted a more upstream regulatory approach around
      restrictions on availability with less emphasis on co-ordinated screening and
      treatment measures. CONCLUSION: New powers over alcohol policy for LAs in England
      can produce markedly different policies for reducing alcohol-related harm. These
      difference are rooted in economic, opportunistic, organisational and personnel
      factors particular to the LAs themselves and may lead to closely tailored
      solutions in some policy areas and poorer co-ordination and attention in others.

PMID- 29047391
TI  - Report of a case combining solitary Peutz-Jeghers polyp, colitis cystica
      profunda, and high-grade dysplasia of the epithelium of the colon.
AB  - BACKGROUND: Colitis cystica profunda is a rare nonneoplastic disease defined by
      the presence of intramural cysts that contain mucus, usually situated in the
      rectosigmoid area, which can mimic various malignant lesions and polyps. Its
      etiology still remains not fully elucidated, and several mechanisms such as
      congenital, post-traumatic, and infectious have been implicated in the
      development of this rare entity. CASE PRESENTATION: Herein, we describe a unique
      case of colitis cystica profunda in the setting of Peutz-Jeghers-type polyp of
      the sigmoid colon, associated with high-grade dysplasia of the overlying
      epithelium in a 48-year-old female patient, who presented to the emergency room
      with signs of intestinal obstruction. To the best of our insight, this is the
      first manifestation ever reported in the literature regarding the coexistence of
      solitary Peutz-Jeghers-type polyp, colitis cystica profunda, and high-grade
      dysplasia of the epithelium of the colon. CONCLUSIONS: The purpose of this case
      report is to highlight colitis cystica profunda and its clinical significance. An
      uncommon nonneoplastic entity, many times masquerading as malignant lesion of the
      rectosigmoid area of the colon. Clinicians and pathologists should be aware of
      this benign condition that is found incidentally postoperatively in patients
      undergoing colectomies, leading to unnecessary increase of morbidity and
      mortality in these patients, who otherwise could have been cured with
      conservative treatment only.

PMID- 29047390
TI  - Roles of BCCIP deficiency in mammary tumorigenesis.
AB  - BACKGROUND: Dysregulated DNA repair and cell proliferation controls are essential
      driving forces in mammary tumorigenesis. BCCIP was originally identified as a
      BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of
      genomic stability, cell cycle regulation, and microtubule dynamics. The aims of
      this study were to determine whether BCCIP deficiency contributes to mammary
      tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality,
      and to reveal the mechanistic implications of BCCIP in breast cancer
      interventions. METHODS: We analyzed the BCCIP protein level in 470 cases of human
      breast cancer to determine the associations between BCCIP and 53BP1, p53, and
      subtypes of breast cancer. We further constructed a unique BCCIP knockdown mouse
      model to determine whether a partial BCCIP deficiency leads to spontaneous breast
      cancer formation. RESULTS: We found that the BCCIP protein level is downregulated
      in 49% of triple-negative breast cancer and 25% of nontriple-negative breast
      cancer. The downregulation of BCCIP is mutually exclusive with p53 mutations but
      concurrent with 53BP1 loss in triple-negative breast cancer. In a K14-Cre
      mediated conditional BCCIP knockdown mouse model, we found that BCCIP
      downregulation causes a formation of benign modules in the mammary glands,
      resembling the epidermal inclusion cyst of the breast. However, the majority of
      these benign lesions remain indolent, and only ~ 10% of them evolve into
      malignant tumors after a long latency. This tumor progression is associated with
      a loss of 53BP1 and p16 expression. BCCIP knockdown did not alter the latency of
      mammary tumor formation induced by conditional Trp53 deletion. CONCLUSIONS: Our
      data suggest a confounding role of BCCIP deficiency in modulating breast cancer
      development by enhancing tumor initiation but hindering progression. Furthermore,
      secondary genetic alternations may overcome the progression suppression imposed
      by BCCIP deficiency through a synthetic viability mechanism.

PMID- 29047392
TI  - Correction to: Report from the 2nd Cardiovascular Outcome Trial (CVOT) Summit of
      the Diabetes and Cardiovascular Disease (D&CVD) EASD Study Group.
AB  - Following publication of the original article [1], author Antonio Ceriello
      requested that a correction be published in relation to his affiliations. His
      correct affiliations have been updated in this erratum. This correction is very
      important for the correct assignment of funds to his Institutions.

PMID- 29047393
TI  - The Human Behaviour-Change Project: harnessing the power of artificial
      intelligence and machine learning for evidence synthesis and interpretation.
AB  - BACKGROUND: Behaviour change is key to addressing both the challenges facing
      human health and wellbeing and to promoting the uptake of research findings in
      health policy and practice. We need to make better use of the vast amount of
      accumulating evidence from behaviour change intervention (BCI) evaluations and
      promote the uptake of that evidence into a wide range of contexts. The scale and
      complexity of the task of synthesising and interpreting this evidence, and
      increasing evidence timeliness and accessibility, will require increased computer
      support. The Human Behaviour-Change Project (HBCP) will use Artificial
      Intelligence and Machine Learning to (i) develop and evaluate a 'Knowledge
      System' that automatically extracts, synthesises and interprets findings from BCI
      evaluation reports to generate new insights about behaviour change and improve
      prediction of intervention effectiveness and (ii) allow users, such as
      practitioners, policy makers and researchers, to easily and efficiently query the
      system to get answers to variants of the question 'What works, compared with
      what, how well, with what exposure, with what behaviours (for how long), for
      whom, in what settings and why?'. METHODS: The HBCP will: a) develop an ontology
      of BCI evaluations and their reports linking effect sizes for given target
      behaviours with intervention content and delivery and mechanisms of action, as
      moderated by exposure, populations and settings; b) develop and train an
      automated feature extraction system to annotate BCI evaluation reports using this
      ontology; c) develop and train machine learning and reasoning algorithms to use
      the annotated BCI evaluation reports to predict effect sizes for particular
      combinations of behaviours, interventions, populations and settings; d) build
      user and machine interfaces for interrogating and updating the knowledge base;
      and e) evaluate all the above in terms of performance and utility. DISCUSSION:
      The HBCP aims to revolutionise our ability to synthesise, interpret and deliver
      evidence on behaviour change interventions that is up-to-date and tailored to
      user need and context. This will enhance the usefulness, and support the
      implementation of, that evidence.

PMID- 29047394
TI  - EsPRit: ethics committee proposals for Long Term Medical Data Registries in
      rapidly evolving research fields - a future-proof best practice approach.
AB  - BACKGROUND: Long-term data collection is a challenging task in the domain of
      medical research. Many effects in medicine require long periods of time to become
      traceable e.g. the development of secondary malignancies based on a given
      radiotherapeutic treatment of the primary disease. Nevertheless, long-term
      studies often suffer from an initial lack of available information, thus
      disallowing a standardized approach for their approval by the ethics committee.
      This is due to several factors, such as the lack of existing case report forms or
      an explorative research approach in which data elements may change over time. In
      connection with current medical research and the ongoing digitalization in
      medicine, Long Term Medical Data Registries (MDR-LT) have become an important
      means of collecting and analyzing study data. As with any clinical study, ethical
      aspects must be taken into account when setting up such registries. This work
      addresses the problem of creating a valid, high-quality ethics committee proposal
      for medical registries by suggesting groups of tasks (building blocks),
      information sources and appropriate methods for collecting and analyzing the
      information, as well as a process model to compile an ethics committee proposal
      (EsPRit). METHODS: To derive the building blocks and associated methods software
      and requirements engineering approaches were utilized. Furthermore, a process
      oriented approach was chosen, as information required in the creating process of
      ethics committee proposals remain unknown in the beginning of planning an MDR-LT.
      Here, we derived the needed steps from medical product certification. This was
      done as the medical product certification itself also communicates a process
      oriented approach rather than merely focusing on content. A proposal was created
      for validation and inspection of applicability by using the proposed building
      blocks. The proposed best practice was tested and refined within SEMPER
      (Secondary Malignoma - Prospective Evaluation of the Radiotherapeutics dose
      distribution as the cause for induction) as a case study. RESULTS: The proposed
      building blocks cover the topics of "Context Analysis", "Requirements Analysis",
      "Requirements Validation", "Electronic Case Report (eCRF) Design" and "Overall
      Concept Creation". Additional methods are attached with regards to each topic.
      The goals of each block can be met by applying those methods. The proposed
      methods are proven methods as applied in e.g. existing Medical Data Registry
      projects, as well as in software or requirements engineering. CONCLUSION: Several
      building blocks and attached methods could be identified in the creation of a
      generic ethics committee proposal. Hence, an Ethics Committee can make informed
      decisions on the suggested study via said blocks, using the suggested methods
      such as "Defining Clinical Questions" within the Context Analysis. The study
      creators have to confirm that they adhere to the proposed procedure within the
      ethic proposal statement. Additional existing Medical Data Registry projects can
      be compared to EsPRit for conformity to the proposed procedure. This allows for
      the identification of gaps, which can lead to amendments requested by the ethics
      committee.

PMID- 29047396
TI  - Correction to: Oral health literacy and oral health outcomes in an adult
      population in Brazil.

PMID- 29047395
TI  - Cellular and molecular characterization of gametogenic progression in ex vivo
      cultured prepuberal mouse testes.
AB  - BACKGROUND: Recently, an effective testis culture method using a gas-liquid
      interphase, capable of differentiate male germ cells from neonatal spermatogonia
      to spermatozoa has been developed. Nevertheless, this methodology needs deep
      analyses that allow future experimental approaches in basic, pathologic and/or
      reprotoxicologic studies. Because of this, we characterized at cellular and
      molecular levels the entire in vitro spermatogenic progression, in order to
      understand and evaluate the characteristics that define the spermatogenic process
      in ex vivo cultured testes compared to the in vivo development. METHODS:
      Testicular explants of CD1 mice aged 6 and 10 days post-partum were respectively
      cultured during 55 and 89 days. Cytological and molecular approaches were
      performed, analyzing germ cell proportion at different time culture points,
      meiotic markers immunodetecting synaptonemal complex protein SYCP3 by
      immunocytochemistry and the relative expression of different marker genes along
      the differentiation process by Reverse Transcription - quantitative Polymerase
      Chain Reaction. In addition, microRNA and piwi-interactingRNA profiles were also
      evaluated by Next Generation Sequencing and bioinformatic approaches. RESULTS:
      The method promoted and maintained the spermatogenic process during 89 days. At a
      cytological level we detected spermatogenic development delays of cultured
      explants compared to the natural in vivo process. The expression of different
      spermatogenic stages gene markers correlated with the proportion of different
      cell types detected in the cytological preparations. CONCLUSIONS: In vitro
      progression analysis of the different spermatogenic cell types, from both 6.5 dpp
      and 10.5 dpp testes explants, has revealed a relative delay in relation to in
      vivo process. The expression of the genes studied as biomarkers correlates with
      the cytologically and functional detected progression and differential expression
      identified in vivo. After a first analysis of deep sequencing data it has been
      observed that as long as cultures progress, the proportion of microRNAs declined
      respect to piwi-interactingRNAs levels that increased, showing a similar
      propensity than which happens in in vivo spermatogenesis. Our study allows to
      improve and potentially to control the ex vivo spermatogenesis development,
      opening new perspectives in the reproductive biology fields including male
      fertility.

PMID- 29047397
TI  - Tyrosine kinase 4 is involved in the reproduction of the platyhelminth parasite
      Schistosoma japonicum.
AB  - BACKGROUND: Schistosomiasis is one of the most common parasitic diseases
      affecting millions of humans and animals worldwide. Understanding the signal
      transduction pathways and the molecular basis of reproductive regulation in
      schistosomes is critically important for developing new strategies for preventing
      and treating these infections. Syk kinases regulate the proliferation,
      differentiation, morphogenesis, and survival of various types of cells and have
      been identified in invertebrates. Tyrosine kinase 4 (TK4), a member of the Syk
      kinase family, plays a pivotal role in gametogenesis in S. mansoni, affecting the
      development of the testis and ovaries in this parasite. The role of TK4, however,
      in the reproduction of S. japonicum is poorly understood. METHODS: Here, the
      complete coding sequence of TK4 gene in S. japonicum (SjTK4) was cloned and
      characterized. The expression of SjTK4 was analyzed at different life-cycle
      stages and in various tissues of S. japonicum by qPCR. Piceatannol, a Syk kinase
      inhibitor, was applied to S. japonicum in vitro. The piceatannol-induced
      morphological changes of the parasites were observed using confocal laser
      scanning microscopy and the alterations in important egg-shell synthesis-related
      genes were examined using qPCR analyses. RESULTS: SjTK4 mRNA was differentially
      expressed throughout the life-cycle of S. japonicum. SjTK4 mRNA was highly
      expressed in the ovary and testis of S. japonicum, with the level of gene
      expression significantly higher in males than in females. The expression levels
      of some important egg-shell synthesis related genes were higher in the
      piceatannol-treated groups than in the vehicle-treated control group and the
      number of eggs and germ cells also decreased in a concentration-dependent manner.
      Importantly, large pore-like structures can be found in the testis and ovaries of
      males and females after treating with piceatannol. CONCLUSION: The results
      suggest that SjTK4 may play an important role in regulating gametogenesis of S.
      japonicum. The findings may help better understand the fundamental biology of S.
      japonicum. Moreover, the effect of S. japonicum treatment by piceatannol provides
      us with a new idea that inhibition of SjTK4 signaling pathway can effectively
      retard the development of the testis and ovaries.

PMID- 29047398
TI  - Microscopic and molecular analysis of Babesia canis in archived and diagnostic
      specimens reveal the impact of anti-parasitic treatment and postmortem changes on
      pathogen detection.
AB  - BACKGROUND: Classification of Babesia parasites has traditionally relied on
      morphological differentiation based on piroplasm size and shape. Molecular typing
      has subsequently revealed a more complex taxonomy for these piroplasms than
      previously thought. To evaluate the factors that influence the morphology of
      Babesia species upon microscopic examination and hence, their taxonomic
      classification, we performed detailed characterizations of piroplasms from
      archival and prospective collections of cytological samples of dogs with
      piroplasmosis before and after death. Merozoite morphology and time of parasite
      disappearance following imidocarb dipropionate was also investigated. METHODS:
      The study was divided into a (i) review of archived cytological slides from
      confirmed cases of canine piroplasmosis, and (ii) a prospective study of smears
      and tissue imprints from 15 recently necropsied dogs. The latter group could be
      further sub-divided into a non-treated group and an imidocarb dipropionate
      treated group. Exact times of treatment before death were reviewed. Additional
      blood smears prepared from the live dogs and taken before therapy were also
      evaluated in the latter group. Parasite burden per each slide was determined in
      both studies. The shape and size of merozoites were described from blood smears
      taken while the dogs were alive and from different organs during necropsy. The
      results of all measurements were statistically analyzed. RESULTS: The morphology
      and size of merozoites from live dogs corresponded to that of previously
      described 'large' Babesia. The morphology and size of merozoites were
      significantly different (P < 0.001) in postmortem samples, however, and more
      consistent in shape and size with piroplasm cells previously referred to as
      'small' Babesia. PCR and sequencing confirmed B. canis as the causative agent of
      disease in all investigated dogs, including in postmortem negative tissue
      imprints from dogs treated at least 24 h before death. CONCLUSIONS: Changes in
      the morphology of 'large' B. canis to 'small'-like Babesia observed by light
      microscopy appear to represent a common postmortem change. Classification of
      Babesia parasites into 'large' and 'small' Babesia using only microscopy of
      postmortem slides should be treated with caution. PCR-based methodologies for
      detection and molecular typing of Babesia spp. may prove valuable for
      investigating suspected cases of babesiosis following necropsy.

PMID- 29047401
TI  - Correction to: Potent and reversible lentiviral vector restriction in murine
      induced pluripotent stem cells.
AB  - The authors wish to apologize for an error within the scale bar of the microarray
      heatmap in Additional File 5 of the supplementary information. Two values were
      incorrectly displayed on the scale bar (11 instead of 10 and 13 instead of 12).

PMID- 29047399
TI  - Pathogen communities of songbird-derived ticks in Europe's low countries.
AB  - BACKGROUND: Birds play a major role in the maintenance of enzootic cycles of
      pathogens transmitted by ticks. Due to their mobility, they affect the spatial
      distribution and abundance of both ticks and pathogens. In the present study, we
      aim to identify members of a pathogen community [Borrelia burgdorferi (s.l.), B.
      miyamotoi, 'Ca. Neoehrlichia mikurensis', Anaplasma phagocytophilum and
      Rickettsia helvetica] in songbird-derived ticks from 11 locations in the
      Netherlands and Belgium (2012-2014). RESULTS: Overall, 375 infested songbird
      individuals were captured, belonging to 35 species. Thrushes (Turdus iliacus, T.
      merula and T. philomelos) were trapped most often and had the highest mean
      infestation intensity for both Ixodes ricinus and I. frontalis. Of the 671 bird
      derived ticks, 51% contained DNA of at least one pathogenic agent and 13% showed
      co-infections with two or more pathogens. Borrelia burgdorferi (s.l.) DNA was
      found in 34% of the ticks of which majority belong to so-called avian Borrelia
      species (distribution in Borrelia-infected ticks: 47% B. garinii, 34% B.
      valaisiana, 3% B. turdi), but also the mammal-associated B. afzelii (16%) was
      detected. The occurrence of B. miyamotoi was low (1%). Prevalence of R. helvetica
      in ticks was high (22%), while A. phagocytophilum and 'Ca. N. mikurensis'
      prevalences were 5% and 4%, respectively. The occurrence of B. burgdorferi (s.l.)
      was positively correlated with the occurrence of 'Ca. N. mikurensis', reflecting
      variation in susceptibility among birds and/or suggesting transmission
      facilitation due to interactions between pathogens. CONCLUSIONS: Our findings
      highlight the contribution of European songbirds to co-infections in tick
      individuals and consequently to the exposure of humans to multiple pathogens
      during a tick bite. Although poorly studied, exposure to and possibly also
      infection with multiple tick-borne pathogens in humans seems to be the rule
      rather than the exception.

PMID- 29047400
TI  - Observation of the influences of diosgenin on aging ovarian reserve and function
      in a mouse model.
AB  - BACKGROUND: The aim of this study was to investigate the impact of diosgenin, an
      important monomer of sapogenins in yams, on ovarian reserve in a natural aging
      mice model. STUDY DESIGN: This randomized controlled trial included 60 9-month
      old C57 naturally aging female mice. Twenty-one mice were assigned to the dio
      group and were fed a single dose of diosgenin (200 mg/kg/day) suspended in 0.3%
      CMC. Twenty mice were assigned to the DHEA group and were fed a single dose of
      DHEA (1.25 mg/kg/day) suspended in 0.3% CMC. The remaining 20 mice were assigned
      to the old control group and were fed a single dose of 0.3% CMC. Three months
      later, the reproductive performance of these female mice was determined by
      evaluating ovarian follicles and oocyte number and quality in IVF and comparing
      age-matched and young controls. The impact of NOBOX, GDF9 and BMP15 mRNA
      expression was also evaluated. RESULTS: Diosgenin improves ovarian reserve in
      naturally aging mice in terms of increasing the number of primary follicles (P <
      0.05) and serum levels of AMH (P < 0.05). CONCLUSIONS: Diosgenin could counteract
      age-associated ovarian dysfunction by improving the ovarian reserve in a natural
      aging mice model.

PMID- 29047403
TI  - Successful treatment of a recurrent granulation polyp in the airways with high
      dose-rate brachytherapy: a case report.
AB  - BACKGROUND: Benign central airway tumors are very rare diseases. Their unspecific
      symptoms are responsible for late diagnosis. Endoscopic interventions with
      different techniques and tools are widely used for their treatment. However, in
      certain cases interventional endoscopy might be unsuccessful and therefore other
      methods such as high-dose-rate brachytherapy could be a therapeutic option. CASE
      PRESENTATION: A 76-year-old white German woman was referred to our clinic for an
      endoscopic treatment of a recurrent granulation polyp in her left main bronchus.
      She had dyspnea, coughing, and mucus retention. Three times resections via
      bronchoscopy were performed within less than a year. After each intervention the
      polyp regrew inside her left main bronchus causing a repeat of the initial
      symptoms. She presented to our clinic less than 1 month since the last
      intervention. Twice we performed a rigid bronchoscopy in total anesthesia where
      we resected the granulation polyp with a snare wire loop and did an argon plasma
      coagulation of its base. Due to the recurrent growing of the granuloma, we
      performed a high-dose-rate brachytherapy in conscious sedation after another
      interventional bronchoscopy with a resection of the polyp and argon plasma
      coagulation of the base. Three months after brachytherapy our patient came to our
      clinic for a follow-up with none of the initial symptoms. Only a small remnant of
      the polyp without a significant occlusion of her bronchus was visualized by
      bronchoscopy. Furthermore, 6 months after brachytherapy she was not presenting
      any of the initial symptoms. CONCLUSIONS: This case report shows that high-dose
      rate brachytherapy is a therapeutic option for the treatment of benign airway
      stenosis when other interventional treatments are not or are less than
      successful. However, further investigations are needed to prove the effectiveness
      and reliability of the method.

PMID- 29047402
TI  - Associations of physical activity and sedentary behavior during pregnancy with
      gestational diabetes mellitus among Asian women in Singapore.
AB  - BACKGROUND: Few studies have investigated physical activity (PA) and sedentary
      behavior (SB) in relation to fasting (FG) and 2-h postprandial plasma glucose
      (2hPG) levels and gestational diabetes mellitus (GDM); we investigated these
      associations among Asian pregnant women. METHODS: As part of the Growing Up in
      Singapore Towards healthy Outcomes cohort study, PA and SB (sitting and
      television times) were assessed by interviewer-administered questionnaire. During
      75 g oral glucose tolerance tests at 26-28 weeks' gestation we measured FG, 2hPG
      levels and GDM (FG >= 7.0 mmol/L and/or 2hPG >= 7.8 mmol/L). Associations were
      analysed by multiple linear and logistic regression. RESULTS: Among the 1083
      women studied, 18.6% had GDM. SB was not associated with FG, 2hPG and GDM. Higher
      categories of PA were associated with lower 2hPG and a lower likelihood of GDM (p
      trend < 0.05), but not with FG levels. Compared to insufficiently active women,
      highly active women had lower 2hPG levels [beta (95% CI): -0.32 (-0.59, -0.05), p
      = 0.020) and were less likely to have GDM [OR: 0.56 (0.32-0.98), p = 0.040].
      Stratified analysis revealed no associations among under/normal-weight women, but
      significant associations among overweight/obese women; in those with BMI >=23
      kg/m2, sufficiently active and highly active women were less likely to have GDM
      [OR: 0.52, (0.29-0.93), p = 0.028, and OR: 0.34, (0.15-0.77), p = 0.010,
      respectively]. CONCLUSION: Higher PA was associated with lower 2hPG levels and a
      lower prevalence of GDM, particularly in overweight/obese women. Further studies
      are warranted to confirm these findings, and to examine the effectiveness of PA
      promotion strategies for the prevention of gestational hyperglycemia.

PMID- 29047404
TI  - Structural and functional characterization of the divergent Entamoeba Src using
      Src inhibitor-1.
AB  - BACKGROUND: The abundant number of kinases that Entamoeba histolytica possesses
      allows us to assume that the regulation of cellular functions by phosphorylation
      dephosphorylation processes is very important. However, the kinases responsible
      for the phosphorylation in Entamoeba spp. vary in the structure of their domains
      and, therefore, could be responsible for the unusual biological characteristics
      of this parasite. In higher eukaryotes, Src kinases share conserved structural
      domains and are very important in the regulation of the actin cytoskeleton. In
      both Entamoeba histolytica and Entamoeba invadens, the major Src kinase homologue
      of higher eukaryotes lacks SH3 and SH2 domains, but does have KELCH domains; the
      latter are part of actin cross-linking proteins in higher eukaryotic cells.
      METHODS: The function of the EhSrc protein kinase of Entamoeba spp. was evaluated
      using Src inhibitor-1, microscopy assays, Src kinase activity and western blot.
      In addition, to define the potential inhibitory mechanism of Src-inhibitor-1 for
      the amoebic EhSrc protein kinase, molecular dynamic simulations using NAnoscale
      Molecular Dynamics (NAMD2) program and docking studies were performed with MOE
      software. RESULTS: We demonstrate that Src inhibitor-1 is able to prevent the
      activity of EhSrc protein kinase, most likely by binding to the catalytic domain,
      which affects cell morphology via the disruption of actin cytoskeleton remodeling
      and the formation of phagocytic structures without an effect on cell adhesion.
      Furthermore, in E. invadens, Src inhibitor-1 inhibited the encystment process by
      blocking RhoA GTPase activity, a small GTPase protein of Rho family. CONCLUSIONS:
      Even though the EhSrc molecule of Entamoeba is not a typical Src, because its
      divergent amino acid sequence, it is a critical factor in the biology of this
      parasite via the regulation of actin cytoskeleton remodeling via RhoA GTPase
      activation. Based on this, we conclude that EhSrc could become a target molecule
      for the future design of drugs that can prevent the transmission of the disease.

PMID- 29047405
TI  - Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head.
AB  - BACKGROUND: ANFH is a major health problem, to which long lasting and definitive
      treatments are lacking. The aim of this study is to study RNA alterations
      attributed to cortisol-induced ANFH. METHODS: Rat models were stratified into
      three groups: in vitro group (n = 20) for molecular biological assays, control
      group (n = 3), and ANFH group induced using lipopolysaccharide and dexamethasone
      (n = 3). Bone marrow-derived endothelial progenitor cells (BM-EPCs) were
      extracted from the rats. An RNA expression array was performed on BM-EPCs, and
      enriched genes were subject to pathway analysis. In vitro studies following
      findings of array results were also performed using the isolated BM-EPCs.
      RESULTS: Significant alterations in mammalian target of rapamycin (mTOR) and HIF
      signaling pathways were identified in BM-EPCs of ANFH. By applying cortisol and
      dexamethasone to BM-EPCs, significant changes in mTOR and HIF elements were
      identified. The alteration of HIF pathways appeared to be downstream of mTOR
      signaling. Glucocorticoid receptor (GR) expression was related to glucocorticoid
      dependent mRNA expression of mTOR/HIF genes. mTOR-dependent angiogenesis but not
      anabolism was the target of GR in ANFH. Inhibition of mTOR signaling also induced
      apoptosis of BM-EPCs via CHOP-dependent DR5 induction in response to GR
      stimulation. CONCLUSION: Decreased mTOR signaling in response to GR stimulation
      leading to downregulated HIF pathway as well as increased apoptosis could be the
      pathophysiology.

PMID- 29047406
TI  - Loss of MKP-5 promotes myofiber survival by activating STAT3/Bcl-2 signaling
      during regenerative myogenesis.
AB  - BACKGROUND: The mitogen-activated protein kinases (MAPKs) have been shown to be
      involved in regulating myofiber survival. In skeletal muscle, p38 MAPK and JNK
      are negatively regulated by MAPK phosphatase-5 (MKP-5). During muscle
      regeneration, MKP-5 is downregulated, thereby promoting p38 MAPK/JNK signaling,
      and subsequent repair of damaged muscle. Mice lacking MKP-5 expression exhibit
      enhanced regenerative myogenesis. However, the effect of MKP-5 on myofiber
      survival during regeneration is unclear. METHODS: To investigate whether MKP-5 is
      involved in myofiber survival, skeletal muscle injury was induced by cardiotoxin
      injection, and the effects on apoptosis were assessed by TUNEL assay in wild type
      and MKP-5-deficient mice. The contribution of MKP-5 to apoptotic signaling and
      its link to this pathway through mitochondrial function were determined in
      regenerating skeletal muscle of MKP-5-deficient mice. RESULTS: We found that loss
      of MKP-5 in skeletal muscle resulted in improved myofiber survival. In response
      to skeletal muscle injury, loss of MKP-5 decreased activation of the
      mitochondrial apoptotic pathway involving the signal transducer and activator of
      transcription 3 (STAT3) and increased expression of the anti-apoptotic
      transcription factor Bcl-2. Skeletal muscle of MKP-5-deficient mice also
      exhibited an improved anti-oxidant capacity as a result of increased expression
      of catalase further contributing to myofiber survival by attenuating oxidative
      damage. CONCLUSIONS: Taken together, these findings suggest that MKP-5
      coordinates skeletal muscle regeneration by regulating mitochondria-mediated
      apoptosis. MKP-5 negatively regulates apoptotic signaling, and during
      regeneration, MKP-5 downregulation contributes to the restoration of myofiber
      survival. Finally, these results suggest that MKP-5 inhibition may serve as an
      important therapeutic target for the preservation of skeletal muscle survival in
      degenerative muscle diseases.

PMID- 29047407
TI  - A web-based collection of genotype-phenotype associations in hereditary recurrent
      fevers from the Eurofever registry.
AB  - BACKGROUND: Hereditary recurrent fevers (HRF) are a group of rare monogenic
      diseases leading to recurrent inflammatory flares. A large number of variants has
      been described for the four genes associated with the best known HRF, namely
      MEFV, NLRP3, MVK, TNFRSF1A. The Infevers database (
      http://fmf.igh.cnrs.fr/ISSAID/infevers ) is a large international registry
      collecting variants reported in these genes. However, no genotype-phenotype
      associations are provided, but only the clinical phenotype of the first
      patient(s) described for each mutation. The aim of this study is to develop a
      registry of genotype-phenotype associations observed in patients with HRF,
      enrolled and validated in the Eurofever registry. RESULTS: Genotype-phenotype
      associations observed in all the patients with HRF enrolled in the Eurofever
      registry were retrospectively analyzed. For autosomal dominant diseases (CAPS and
      TRAPS), all mutations were individually analyzed. For autosomal recessive
      diseases (FMF and MKD), homozygous and heterozygous combinations were described.
      Mean age of onset, disease course (recurrent or chronic), mean duration of fever
      episodes, clinical manifestations associated with fever episodes, atypical
      manifestations, complications and response to treatment were also studied. Data
      observed in 751 patients (346 FMF, 133 CAPS, 114 MKD, 158 TRAPS) included in the
      Eurofever registry and validated by experts were summarized in Tables. A total of
      149 variants were described: 46 TNFRSF1A and 27 NLRP3 variants, as well as
      various combinations of 48 MVK and 28 MEFV variants were available. CONCLUSIONS:
      We provide a potentially useful tool for physicians dealing with HRF, namely a
      registry of genotype-phenotype associations for patients enrolled in the
      Eurofever registry. This tool is complementary to the Infevers database and will
      be available at the Eurofever and Infevers websites.

PMID- 29047408
TI  - The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia
      (RICH trial): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Cisplatin is a key drug in lung cancer therapy. However, cisplatin is
      also well known to induce gastrointestinal disorders, such as chemotherapy
      induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes
      affect patients' quality of life and make continuation of chemotherapy difficult.
      Anorexia is a cause of concern for patients with cancer because a persistent loss
      of appetite progresses to cancer cachexia. Although evidence-based management for
      chemotherapy has recently been established, there is room for improvement.
      METHODS/DESIGN: This placebo-controlled, double-blind, randomized trial will aim
      to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito
      (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in
      patients with lung cancer. Patients with lung cancer who plan to receive
      cisplatin-including chemotherapy will be recruited. Patients who provide written
      consent will be randomly allocated to receive either TJ-43 (arm A) or placebo
      (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators
      and patients will be masked to the treatment assignment throughout the trial. The
      primary endpoint will be evaluated as the change in dietary intake from day 0
      (the day before the start of chemotherapy) to day 7 of cisplatin-including
      chemotherapy. The two arms of the trial will comprise 30 patients each. From
      November 2014, a total of 60 patients will be recruited, and recruitment for the
      study is planned to be complete by October 2017. DISCUSSION: This trial is
      designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and
      maintaining food intake caused by cisplatin-including chemotherapy in patients
      with lung cancer. TRIAL REGISTRATION: Japan Pharmaceutical Information Center
      Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 .
      Registered on 15 December 2014; the RICH trial.

PMID- 29047409
TI  - Novel approach to gastric mucosal defect repair using fresh amniotic membrane
      allograft in dogs (experimental study).
AB  - BACKGROUND: Gastric mucosal defect could result from several causative factors
      including the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori
      infection, gastrointestinal and spinal cord diseases, and neoplasia. This study
      was performed to achieve a novel simple, inexpensive, and effective surgical
      technique for the repair of gastric mucosal defect. METHODS: Six adult male
      mongrel dogs were divided into two groups (three dogs each). In the control
      positive group (C + ve), dogs were subjected to surgical induction of gastric
      mucosal defect and then treated using traditional medicinal treatment for such a
      condition. In the amniotic membrane (AM) group, dogs were subjected to the same
      operation and then fresh AM allograft was applied. Clinical, endoscopic,
      biochemical (serum protein and lipid and pepsin activity in gastric juice),
      histopathological, and immunohistochemistry evaluations were performed. RESULTS:
      Regarding endoscopic examination, there was no sign of inflammatory reaction
      around the grafted area in the AM group compared to the C + ve group. The
      leukocytic infiltration in the gastric ulcer was well detected in the control
      group and was less observed in the AM group. In the AM group, the concentrations
      of both protein and lipid profiles were nearly the same as those in serum samples
      taken preoperatively at zero time, which indicated that the AM grafting acted the
      same as gastric mucosa. The re-epithelization of the gastric ulcer in the C + ve
      group was not yet detected at 21 days, while in the AM group it was well observed
      covering most of the gastric ulcer. AM accelerated the re-epithelization of the
      gastric ulcer. The fibrous connective tissue and the precursor of collagen (COL
      IA1) were poorly detected in the gastric ulcer with AM application. CONCLUSION:
      Using fresh AM allograft for repairing gastric mucosal defect in dogs showed
      great impact as a novel method to achieve optimum reconstruction of the gastric
      mucosal architecture and restoration of pre-epithelial, epithelial, and post
      epithelial normal gastric mucosal barriers.

PMID- 29047410
TI  - Association between kidney intracapsular pressure and ultrasound elastography.
AB  - BACKGROUND: Kidney congestion is a common pathophysiologic pathway of acute
      kidney injury (AKI) in sepsis and heart failure. There is no noninvasive tool to
      measure kidney intracapsular pressure (KIP) directly. METHODS: We evaluated the
      correlation of KIP with kidney elasticity measured by ultrasound surface wave
      elastography (USWE). We directly measured transcatheter KIP in three pigs at
      baseline and after bolus infusion of normal saline, norepinephrine, vasopressin,
      dopamine, and fenoldopam; infiltration of 2-L peritoneal dialysis solution in the
      intra-abdominal space; and venous, arterial, and ureteral clamping. KIP was
      compared with USWE wave speed. RESULTS: Only intra-abdominal installation of
      peritoneal dialysis fluid was associated with significant change in KIP (mean
      (95% CI) increase, 3.7 (3.2-4.2)] mmHg; P < .001). Although intraperitoneal
      pressure and KIP did not differ under any experimental condition, bladder
      pressure was consistently and significantly greater than KIP under all
      circumstances (mean (95% CI) bladder pressure vs. KIP, 3.8 (2.9-4.) mmHg; P <
      .001). USWE wave speed significantly correlated with KIP (adjusted coefficient of
      determination, 0.71; P < .001). Estimate (95% CI) USWE speed for KIP prediction
      stayed significant after adjustment for KIP hypertension (-0.8 (- 1.4 to - 0.2)
      m/s; P = .008) whereas systolic and diastolic blood pressures were not
      significant predictors of KIP. CONCLUSIONS: In a pilot study of the swine model,
      we found ultrasound surface wave elastography speed is significantly correlated
      with transcatheter measurement of kidney intracapsular and intra-abdominal
      pressures, while bladder pressure overestimated kidney intracapsular pressure.

PMID- 29047412
TI  - Wetland characteristics linked to broad-scale patterns in Culiseta melanura
      abundance and eastern equine encephalitis virus infection.
AB  - BACKGROUND: Eastern equine encephalitis virus (EEEV) is an expanding mosquito
      borne threat to humans and domestic animal populations in the northeastern United
      States. Outbreaks of EEEV are challenging to predict due to spatial and temporal
      uncertainty in the abundance and viral infection of Cs. melanura, the principal
      enzootic vector. EEEV activity may be closely linked to wetlands because they
      provide essential habitat for mosquito vectors and avian reservoir hosts.
      However, wetlands are not homogeneous and can vary by vegetation, connectivity,
      size, and inundation patterns. Wetlands may also have different effects on EEEV
      transmission depending on the assessed spatial scale. We investigated
      associations between wetland characteristics and Cs. melanura abundance and
      infection with EEEV at multiple spatial scales in Connecticut, USA. RESULTS: Our
      findings indicate that wetland vegetative characteristics have strong
      associations with Cs. melanura abundance. Deciduous and evergreen forested
      wetlands were associated with higher Cs. melanura abundance, likely because these
      wetlands provide suitable subterranean habitat for Cs. melanura development. In
      contrast, Cs. melanura abundance was negatively associated with emergent and
      scrub/shrub wetlands, and wetland connectivity to streams. These relationships
      were generally strongest at broad spatial scales. Additionally, the relationships
      between wetland characteristics and EEEV infection in Cs. melanura were generally
      weak. However, Cs. melanura abundance was strongly associated with EEEV
      infection, suggesting that wetland-associated changes in abundance may be
      indirectly linked to EEEV infection in Cs. melanura. Finally, we found that wet
      hydrological conditions during the transmission season and during the fall/winter
      preceding the transmission season were associated with higher Cs. melanura
      abundance and EEEV infection, indicating that wet conditions are favorable for
      EEEV transmission. CONCLUSIONS: These results expand the broad-scale
      understanding of the effects of wetlands on EEEV transmission and help to reduce
      the spatial and temporal uncertainty associated with EEEV outbreaks.

PMID- 29047413
TI  - iTACTIC - implementing Treatment Algorithms for the Correction of Trauma-Induced
      Coagulopathy: study protocol for a multicentre, randomised controlled trial.
AB  - BACKGROUND: Traumatic injury is the fourth leading cause of death globally. Half
      of all trauma deaths are due to bleeding and most of these will occur within 6 h
      of injury. Haemorrhagic shock following injury has been shown to induce a
      clotting dysfunction within minutes, and this early trauma-induced coagulopathy
      (TIC) may exacerbate bleeding and is associated with higher mortality and
      morbidity. In spite of improved resuscitation strategies over the last decade,
      current transfusion therapy still fails to correct TIC during ongoing haemorrhage
      and evidence for the optimal management of bleeding trauma patients is lacking.
      Recent publications describe increasing the use of Viscoelastic Haemostatic
      Assays (VHAs) in trauma haemorrhage; however, there is insufficient evidence to
      support their superiority to conventional coagulation tests (CCTs).
      METHODS/DESIGN: This multicentre, randomised controlled study will compare the
      haemostatic effect of an evidence-based VHA-guided versus an optimised CCT-guided
      transfusion algorithm in haemorrhaging trauma patients. A total of 392 adult
      trauma patients will be enrolled at major trauma centres. Participants will be
      eligible if they present with clinical signs of haemorrhagic shock, activate the
      local massive haemorrhage protocol and initiate first blood transfusion. Enrolled
      patients will be block randomised per centre to either VHA-guided or CCT-guided
      transfusion therapy in addition to that therapy delivered as part of standard
      care, until haemostasis is achieved. Patients will be followed until discharge or
      28 days. The primary endpoint is the proportion of subjects alive and free of
      massive transfusion (less than 10 units of red blood cells) at 24 h. Secondary
      outcomes include the effect of CCT- versus VHA-guided therapy on organ failure,
      total hospital and intensive care lengths of stay, health care resources needed
      and mortality. Surviving patients will be asked to complete a quality of life
      questionnaire (EuroQol EQ-5DTM) at day 90. DISCUSSION: CCTs have traditionally
      been used to detect TIC and monitor response to treatment in traumatic major
      haemorrhage. The use of VHAs is increasing, but limited evidence exists to
      support the superiority of these technologies (or comparatively) for patient
      centred outcomes. This knowledge gap will be addressed by this trial. TRIAL
      REGISTRATION: ClinicalTrials.gov, ID: NCT02593877 . Registered on 15 October
      2015. Trial sponsor Queen Mary University of London The contact person of the
      above sponsor organisation is: Dr. Sally Burtles, Director of Research Services
      and Business Development, Joint Research Management Office, QM Innovation
      Building, 5 Walden Street, London E1 2EF; phone: 020 7882 7260; Email:
      sponsorsrep@bartshealth.nhs.uk Trial sites Academic Medical Centre, Amsterdam,
      The Netherlands Kliniken der Stadt Koln gGmbH, Cologne, Germany Rigshospitalet
      (Copenhagen University Hospital), Copenhagen, Denmark John Radcliff Hospital,
      Oxford, United Kingdom Oslo University Hospital, Oslo, Norway The Royal London
      Hospital, London, United Kingdom Centre for Trauma Sciences, Blizard Institute,
      Queen Mary University of London, London, United Kingdom Health Economics Research
      Centre, Nuffield Department of Population Health, University of Oxford, Oxford,
      United Kingdom Sites that are planning to start recruitment in mid/late 2017
      Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United
      Kingdom University of Kansas Hospital (UKH), Kansas City, MO, USA Protocol
      version: 3.0/14.03.2017 (Additional file 1).

PMID- 29047411
TI  - Mildly elevated lactate levels are associated with microcirculatory flow
      abnormalities and increased mortality: a microSOAP post hoc analysis.
AB  - BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly
      recognized as a prognostic finding in critically ill patients. One of several
      possible underlying mechanisms, microcirculatory dysfunction, can be assessed at
      the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the
      association between relative hyperlactatemia, microcirculatory flow, and outcome.
      METHODS: This study was a predefined subanalysis of a multicenter international
      point prevalence study on microcirculatory flow abnormalities, the
      Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP).
      Microcirculatory flow abnormalities were assessed with sidestream dark-field
      imaging. Abnormal microcirculatory flow was defined as a microvascular flow index
      (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3
      (continuous flow). Associations between microcirculatory flow abnormalities,
      single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of
      501 patients, lactate levels were available. For this substudy, all 257 patients
      with lactate levels <= 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were
      included. Crude ICU mortality increased with each lactate quartile. In a
      multivariable analysis, a lactate level > 1.5 mmol/L was independently associated
      with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a
      heterogeneous ICU population, a single-spot mildly elevated lactate level (even
      within the reference range) was independently associated with increased mortality
      and microvascular flow abnormalities. In vivo microscopy of the microcirculation
      may be helpful in discriminating between flow- and non-flow-related causes of
      mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01179243 . Registered on August 3, 2010.

PMID- 29047414
TI  - Histone isoform H2A1H promotes attainment of distinct physiological states by
      altering chromatin dynamics.
AB  - BACKGROUND: The distinct functional effects of the replication-dependent histone
      H2A isoforms have been demonstrated; however, the mechanistic basis of the non
      redundancy remains unclear. Here, we have investigated the specific functional
      contribution of the histone H2A isoform H2A1H, which differs from another isoform
      H2A2A3 in the identity of only three amino acids. RESULTS: H2A1H exhibits varied
      expression levels in different normal tissues and human cancer cell lines (H2A1C
      in humans). It also promotes cell proliferation in a context-dependent manner
      when exogenously overexpressed. To uncover the molecular basis of the non
      redundancy, equilibrium unfolding of recombinant H2A1H-H2B dimer was performed.
      We found that the M51L alteration at the H2A-H2B dimer interface decreases the
      temperature of melting of H2A1H-H2B by ~ 3  degrees C as compared to the H2A2A3
      H2B dimer. This difference in the dimer stability is also reflected in the
      chromatin dynamics as H2A1H-containing nucleosomes are more stable owing to M51L
      and K99R substitutions. Molecular dynamic simulations suggest that these
      substitutions increase the number of hydrogen bonds and hydrophobic interactions
      of H2A1H, enabling it to form more stable nucleosomes. CONCLUSION: We show that
      the M51L and K99R substitutions, besides altering the stability of histone
      histone and histone-DNA complexes, have the most prominent effect on cell
      proliferation, suggesting that the nucleosome stability is intimately linked with
      the physiological effects observed. Our work provides insights into the molecular
      basis of the non-redundancy of the histone H2A isoforms that are being
      increasingly reported to be functionally important in varied physiological
      contexts.

PMID- 29047415
TI  - Transgender women in Malaysia, in the context of HIV and Islam: a qualitative
      study of stakeholders' perceptions.
AB  - BACKGROUND: Globally, one of the key groups considered to be at high risk of
      acquiring HIV are transgender women, often a marginalised group. In the Malaysian
      context there has been a scarcity of published research relating to transgender
      women, a sensitive issue in a Muslim majority country, where Islam plays an
      influential role in society. Furthermore, there has been a paucity of research
      relating to how such issues relate to HIV prevention in transgender women in
      Malaysia. Thus, the aim of this study is to explore the attitudes of stakeholders
      involved in HIV prevention policy in Malaysia towards transgender women, given
      the Islamic context. METHODS: In-depth interviews were undertaken with
      stakeholders involved in HIV prevention, Ministry of Health, Religious Leaders
      and People Living with HIV, including transgender women. Thirty five participants
      were recruited using purposive sampling from June to December 2013 within Kuala
      Lumpur and surrounding vicinities. Interviews were in person, audiotaped,
      transcribed verbatim and used a framework analysis. RESULTS: Five central themes
      emerged from the qualitative data; Perceptions of Transgender women and their
      place in Society; Reaching out to Transgender Women; Islamic doctrine; 'Cure',
      'Correction' and finally, Stigma and Discrimination. DISCUSSION: Islamic rulings
      about transgenderism were often the justification given by participants
      chastising transgender women, whilst there were also more progressive attitudes
      and room for debate. Pervasive negative attitudes and stigma and discrimination
      created a climate where transgender women often felt more comfortable with non
      governmental organisations. CONCLUSION: The situation of transgender women in
      Malaysia and HIV prevention is a highly sensitive and challenging environment for
      all stakeholders, given the Muslim context and current legal system. Despite this
      apparent impasse, there are practically achievable areas that can be improved
      upon to optimise HIV prevention services and the environment for transgender
      women in Malaysia.

PMID- 29047417
TI  - Levosimendan for patients with severely reduced left ventricular systolic
      function and/or low cardiac output syndrome undergoing cardiac surgery: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Previous studies have shown beneficial effects of levosimendan in
      high-risk patients undergoing cardiac surgery. Two large randomized controlled
      trials (RCTs), however, showed no advantages of levosimendan. METHODS: We
      performed a systematic review and meta-analysis (MEDLINE and Embase from
      inception until March 30, 2017), investigating whether levosimendan offers
      advantages compared with placebo in high-risk cardiac surgery patients, as
      defined by preoperative left ventricular ejection fraction (LVEF) <= 35% and/or
      low cardiac output syndrome (LCOS). The primary outcomes were mortality at
      longest follow-up and need for postoperative renal replacement therapy (RRT).
      Secondary postoperative outcomes investigated included myocardial injury,
      supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI),
      duration of mechanical ventilation, intensive care unit and hospital lengths of
      stay, and incidence of hypotension during drug infusion. RESULTS: Six RCTs were
      included in the meta-analysis, five of which investigated only patients with LVEF
      <= 35% and one of which included predominantly patients with LCOS. Mortality was
      similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with
      LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by
      levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with
      LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found
      lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR
      0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02),
      and a trend toward lower mechanical support, both overall (p = 0.07) and in
      patients with LVEF < 35% (p = 0.05). CONCLUSIONS: Levosimendan reduces mortality
      in patients with preoperative severely reduced LVEF but does not affect overall
      mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

PMID- 29047416
TI  - Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed
      Parkinson's case.
AB  - [F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high
      affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET
      studies have shown increased tracer retention in patients clinically diagnosed
      with dementia of AD type and mild cognitive impairment in regions that are known
      to contain tau lesions. In vivo uptake has also consistently been observed in
      midbrain, basal ganglia and choroid plexus in elderly individuals regardless of
      their clinical diagnosis, including clinically normal whose brains are not
      expected to harbor tau pathology in those areas. We and others have shown that [F
      18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood
      products on postmortem material; and this is important for the correct
      interpretation of PET images. In the present study, we further investigated [F
      18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson's disease
      (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated
      [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal
      ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the
      PD diagnosis. Phosphor screen and high resolution autoradiography failed to show
      detectable [F-18]-AV-1451 binding in multiple brain regions examined with the
      exception of neuromelanin-containing neurons in the substantia nigra,
      leptomeningeal melanocytes adjacent to ventricles and midbrain, and
      microhemorrhages in the occipital cortex (all reflecting off-target binding), in
      addition to incidental age-related neurofibrillary tangles in the entorhinal
      cortex. Additional legacy postmortem brain samples containing basal ganglia,
      choroid plexus, and parenchymal hemorrhages from 20 subjects with various
      neuropathologic diagnoses were also included in the autoradiography experiments
      to better understand what [F-18]-AV-1451 in vivo positivity in those regions
      means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the
      basal ganglia of the PD case or any of the other subjects. Off-target binding in
      postmortem choroid plexus samples was only observed in subjects harboring
      leptomeningeal melanocytes within the choroidal stroma. Off-target binding to
      parenchymal hemorrhages was noticed in postmortem material from subjects with
      cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this
      PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for
      neurofibrillary tau pathology but also exhibits off-target binding to
      neuromelanin, melanin and blood components. The robust off-target in vivo
      retention in basal ganglia and choroid plexus, in the absence of tau deposits,
      meningeal melanocytes or any other identifiable binding substrate by
      autoradiography in the PD case reported here, also suggests that the PET signal
      in those regions may be influenced, at least in part, by biological or technical
      factors that occur in vivo and are not captured by autoradiography.

PMID- 29047419
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      Taxonomy of Campylobacter and Related Bacteria. Minutes of the meetings,
      September 15th and 18th 2013, Aberdeen, Scotland.

PMID- 29047418
TI  - Primary small cell carcinoma of the breast: a case report.
AB  - BACKGROUND: Neuroendocrine breast cancer is a rare entity that was defined in
      2003 by the World Health Organization as a separate breast cancer subtype. The
      diagnosis of neuroendocrine breast cancer requires the presence of neuroendocrine
      features in at least 50% of malignant cells, the exclusion of non-mammary primary
      tumors, as well as the presence of an in situ component in breast histology. The
      treatment and prognosis of neuroendocrine breast cancer are still not well
      established. Small cell carcinoma of the breast is a subtype of neuroendocrine
      cancer, resembling small cell carcinoma of the lung. It has a very poor prognosis
      and warrants treatment with platinum-based chemotherapy. CASE PRESENTATION: We
      herein report the case of a 47-year-old white woman with a left breast mass that
      was found to be an early-stage, high-grade small cell carcinoma of the breast.
      Positron emission tomography-computed tomography imaging excluded any other
      primary disease. Our patient underwent a left total mastectomy with sentinel
      lymph node biopsy and received cisplatin-based adjuvant chemotherapy. Our patient
      remains free of disease to date. CONCLUSIONS: This case report sheds light on a
      rarely described disease and provides a comprehensive approach to diagnosis and
      management. Neuroendocrine carcinoma of the breast is a well-defined histologic
      subtype of breast cancer. Small cell carcinoma of the breast is a rare subtype of
      neuroendocrine breast cancer. Due to the rarity of this entity, prognosis has
      still not been well established, and treatment has not been standardized,
      cisplatin-based treatment has been used in this case similar to small cell
      carcinoma of the lung.

PMID- 29047420
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      Taxonomy of Campylobacter and Related Bacteria. Minutes of the meetings, August
      27 and August 31 2011, Vancouver, Canada.

PMID- 29047421
TI  - Pedobacter kyonggii sp. nov., a psychrotolerant bacterium isolated from forest
      soil.
AB  - Strain K-4-11-1T, a psychrotolerant, light salmon-coloured, Gram-stain-negative,
      non-motile and rod-shaped bacterium, was isolated from forest soil of Kyonggi
      University, Suwon, South Korea. It was able to grow at 0-32  degrees C, at pH 5.0
      10.0 and with 0-1.5 % (w/v) NaCl. This strain was taxonomically characterized by
      a polyphasic approach. Based on 16S rRNA gene sequence analysis, strain K-4-11-1T
      belongs to the genus Pedobacter and is closely related to Pedobacter
      ginsenosidimutans THG-45T (98.75 % sequence similarity), Pedobacter borealis G-1T
      (98.48 %), Pedobacter terrae DS-57T (98.20 %), Pedobacter agri PB92T (97.92 %)
      and Pedobacter suwonensis 15-52T (97.84 %). The only respiratory quinone was
      menaquinone-7. The major polar lipids were phosphatidylethanolamine and
      unidentified glycolipids. The predominant fatty acids of strain K-4-11-1T were
      summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c), iso-C15 : 0, iso-C17 : 0
      3-OH, anteiso-C17 : 0 and summed feature 9 (iso-C17 : 1omega9c and/or C16 : 0 10
      methyl). The genomic DNA G+C content of this novel strain was 38.3 mol%. The DNA
      DNA relatedness values between strain K-4-11-1T and P. ginsenosidimutans KACC
      14530T, P. borealis KACC 14287T, P. terrae KACC 13766T, P. agri KACC 13768T and
      P. suwonensis KACC 11317T were 40.0, 36.3, 37.0, 32.3 and 29.7 %, respectively.
      The morphological, physiological, chemotaxonomic and phylogenetic analyses
      clearly distinguished this novel strain from its closest phylogenetic neighbours.
      Thus, strain K-4-11-1T represents a novel species of the genus Pedobacter, for
      which the name Pedobacter kyonggii sp. nov. is proposed. The type strain is K-4
      11-1T (=KEMB 9005-574T=KACC 19174T=JCM 31916T).

PMID- 29047422
TI  - Mycoplasma genitalium Infection in Adults Reporting Sexual Contact with Infected
      Partners, Australia, 2008-2016.
AB  - Data on the likelihood of Mycoplasma genitalium infection in sexual contacts,
      particularly for men who have sex with men (MSM), are needed to form an evidence
      base for guidelines. We conducted a cross-sectional analysis of patients
      attending a sexual health clinic in Melbourne, Victoria, Australia, during 2008
      2016. We calculated the proportion of contacts with M. genitalium infection and
      determined factors associated with infection. Among those patients reporting
      sexual contact with an M. genitalium-infected person, 48.2% of women, 31.0% of
      heterosexual men, and 41.7% of MSM were infected. Among heterosexual contacts,
      women were twice as likely to be infected; among MSM, rectal infection was more
      common than urethral infection; and among persons within heterosexual
      partnerships, concordance of infection was high. High positivity among female and
      MSM contacts and high concordance in heterosexual partnerships provide some
      justification for presumptive treatment; however, clinicians should consider
      antimicrobial drug resistance and toxicity of quinolones.

PMID- 29047423
TI  - Antimicrobial Nonsusceptibility of Gram-Negative Bloodstream Isolates, Veterans
      Health Administration System, United States, 2003-20131.
AB  - Bacteremia caused by gram-negative bacteria is associated with serious illness
      and death, and emergence of antimicrobial drug resistance in these bacteria is a
      major concern. Using national microbiology and patient data for 2003-2013 from
      the US Veterans Health Administration, we characterized nonsusceptibility trends
      of community-acquired, community-onset; healthcare-associated, community-onset;
      and hospital-onset bacteremia for selected gram-negative bacteria (Escherichia
      coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter spp.). For
      47,746 episodes of bacteremia, the incidence rate was 6.37 episodes/10,000 person
      years for community-onset bacteremia and 4.53 episodes/10,000 patient-days for
      hospital-onset bacteremia. For Klebsiella spp., P. aeruginosa, and Acinetobacter
      spp., we observed a decreasing proportion of nonsusceptibility across nearly all
      antimicrobial drug classes for patients with healthcare exposure; trends for
      community-acquired, community-onset isolates were stable or increasing. The role
      of infection control and antimicrobial stewardship efforts in inpatient settings
      in the decrease in drug resistance rates for hospital-onset isolates needs to be
      determined.

PMID- 29047424
TI  - Drug-Resistant Tuberculosis among Children, China, 2006-2015.
AB  - Microbial drug resistance has become a major public health concern worldwide. To
      acquire epidemiologic data on drug-resistant tuberculosis (DR TB) among children,
      a major cause of illness and death for this population, we conducted a
      retrospective study of 2006-2015 data from 36 TB prevention and control
      institutions in Shandong Province, China. A total of 14,223 new TB cases, among
      which children (<18 years of age) accounted for only 5.5%, were caused by culture
      confirmed Mycobacterium tuberculosis. Among children with TB, 18.9% had DR TB and
      6.9% had multidrug-resistant TB. Over the past decade, the percentage of DR TB;
      multidrug-resistant TB; and overall first-line drug resistance for isoniazid,
      rifampin, ethambutol, and streptomycin among children increased significantly (at
      least 12%). Understanding the long-term trends of DR TB among children can shed
      light on the performance of TB control programs, thereby contributing to global
      TB control.

PMID- 29047425
TI  - Legionnaires' Disease Outbreak Caused by Endemic Strain of Legionella
      pneumophila, New York, New York, USA, 2015.
AB  - During the summer of 2015, New York, New York, USA, had one of the largest and
      deadliest outbreaks of Legionnaires' disease in the history of the United States.
      A total of 138 cases and 16 deaths were linked to a single cooling tower in the
      South Bronx. Analysis of environmental samples and clinical isolates showed that
      sporadic cases of legionellosis before, during, and after the outbreak could be
      traced to a slowly evolving, single-ancestor strain. Detection of an ostensibly
      virulent Legionella strain endemic to the Bronx community suggests potential risk
      for future cases of legionellosis in the area. The genetic homogeneity of the
      Legionella population in this area might complicate investigations and
      interpretations of future outbreaks of Legionnaires' disease.

PMID- 29047426
TI  - Airborne Transmission of Highly Pathogenic Influenza Virus during Processing of
      Infected Poultry.
AB  - Exposure to infected poultry is a suspected cause of avian influenza (H5N1) virus
      infections in humans. We detected infectious droplets and aerosols during
      laboratory-simulated processing of asymptomatic chickens infected with human-
      (clades 1 and 2.2.1) and avian- (clades 1.1, 2.2, and 2.1) origin H5N1 viruses.
      We detected fewer airborne infectious particles in simulated processing of
      infected ducks. Influenza virus-naive chickens and ferrets exposed to the air
      space in which virus-infected chickens were processed became infected and died,
      suggesting that the slaughter of infected chickens is an efficient source of
      airborne virus that can infect birds and mammals. We did not detect consistent
      infections in ducks and ferrets exposed to the air space in which virus-infected
      ducks were processed. Our results support the hypothesis that airborne
      transmission of HPAI viruses can occur among poultry and from poultry to humans
      during home or live-poultry market slaughter of infected poultry.

PMID- 29047427
TI  - Pregnant Women Hospitalized with Chikungunya Virus Infection, Colombia, 2015.
AB  - In 2015 in Colombia, 60 pregnant women were hospitalized with chikungunya virus
      infections confirmed by reverse transcription PCR. Nine of these women required
      admission to the intensive care unit because of sepsis with hypoperfusion and
      organ dysfunction; these women met the criteria for severe acute maternal
      morbidity. No deaths occurred. Fifteen women delivered during acute infection;
      some received tocolytics to delay delivery until after the febrile episode and
      prevent possible vertical transmission. As recommended by a pediatric
      neonatologist, 12 neonates were hospitalized to rule out vertical transmission;
      no clinical findings suggestive of neonatal chikungunya virus infection were
      observed. With 36 women (60%), follow-up was performed 1 year after acute
      viremia; 13 patients had arthralgia in >2 joints (a relapse of infection).
      Despite disease severity, pregnant women with chikungunya should be treated in
      high-complexity obstetric units to rule out adverse outcomes. These women should
      also be followed up to treat potential relapses.

PMID- 29047429
TI  - Tobacco control: a Foundation too far?

PMID- 29047428
TI  - Symptom- and Laboratory-Based Ebola Risk Scores to Differentiate Likely Ebola
      Infections.
AB  - Rapidly identifying likely Ebola patients is difficult because of a broad case
      definition, overlap of symptoms with common illnesses, and lack of rapid
      diagnostics. However, rapid identification is critical for care and containment
      of contagion. We analyzed retrospective data from 252 Ebola-positive and 172
      Ebola-negative patients at a Sierra Leone Ebola treatment center to develop easy
      to-use risk scores, based on symptoms and laboratory tests (if available), to
      stratify triaged patients by their likelihood of having Ebola infection.
      Headache, diarrhea, difficulty breathing, nausea/vomiting, loss of appetite, and
      conjunctivitis comprised the symptom-based score. The laboratory-based score also
      included creatinine, creatine kinase, alanine aminotransferase, and total
      bilirubin. This risk score correctly identified 92% of Ebola-positive patients as
      high risk for infection; both scores correctly classified >70% of Ebola-negative
      patients as low or medium risk. Clinicians can use these risk scores to gauge the
      likelihood of triaged patients having Ebola while awaiting laboratory
      confirmation.

PMID- 29047430
TI  - WHO launches new leadership, new priorities.

PMID- 29047431
TI  - The link between cancer and obesity.

PMID- 29047432
TI  - Towards a smoke-free world? Philip Morris International's new Foundation is not
      credible.

PMID- 29047433
TI  - Catastrophic medical insurance in China.

PMID- 29047434
TI  - Offline: Jim Kim finds his voice.

PMID- 29047435
TI  - The ACA after the expiry of the budget reconciliation.

PMID- 29047436
TI  - Jiang Baoguo: one, two, three against trauma in China.

PMID- 29047437
TI  - Condemning industry attempts to subvert public policy for a tobacco-free world.

PMID- 29047438
TI  - Nuclear war and public health: rebalancing priorities and global health
      leadership.

PMID- 29047439
TI  - Severity of illness and the weekend effect.

PMID- 29047440
TI  - Charlie Gard and the limits of medicine.

PMID- 29047441
TI  - Severity of illness and the weekend effect - Authors' reply.

PMID- 29047442
TI  - HPV vaccination in China needs to be more cost-effective.

PMID- 29047443
TI  - Department of Error.

PMID- 29047444
TI  - Medical education: what about the barefoot doctors?

PMID- 29047446
TI  - Foundation for a smoke-free world.

PMID- 29047445
TI  - Transport and public health in China: the road to a healthy future.
AB  - Transportation-related risk factors are a major source of morbidity and mortality
      in China, where the expansion of road networks and surges in personal vehicle
      ownership are having profound effects on public health. Road traffic injuries and
      fatalities have increased alongside increased use of motorised transport in
      China, and accident injury risk is aggravated by inadequate emergency response
      systems and trauma care. National air quality standards and emission control
      technologies are having a positive effect on air quality, but persistent air
      pollution is increasingly attributable to a growing and outdated vehicle fleet
      and to famously congested roads. Urban design favours motorised transport, and
      physical activity and its associated health benefits are hindered by poor urban
      infrastructure. Transport emissions of greenhouse gases contribute substantially
      to regional and global climate change, which compound public health risks from
      multiple factors. Despite these complex challenges, technological advances and
      innovations in planning and policy stand to make China a leader in sustainable,
      healthy transportation.

PMID- 29047447
TI  - Nobel Prize awarded for discoveries in circadian rhythm.

PMID- 29047448
TI  - 2017 Roux Prize recipient announced: Samba Sow.

PMID- 29047449
TI  - Highly anisotropic electric conductivity in PAN-based carbon nanofibers.
AB  - In addition to the chemical and physical properties of nanostructures their
      successful utilization for applications is strongly triggered by economic
      aspects. Electrospinning of nanowires from solution followed by subsequent
      annealing steps is a comparably cheap technique to fabricate conductive carbon
      nanofibers (CNF) made from polyacrylonitrile (PAN) molecules in large quantities.
      In this work, we investigated the microscopic properties of the CNFs with
      diameters of 100-300 nm by means of Raman and x-ray photoelectron spectroscopy
      and correlated these results with transport measurements done with a 4-tip STM.
      In particular, we investigated the effect of fiber alignment and knot densities,
      which can be controlled by applying constant creep due to stress during the
      stabilization process. The comparison of the conductivity obtained from single
      CNFs revealed further that the fiber crossings within the ensemble structure act
      as scattering centers and proofs that the transport is along the surfaces of the
      CNFs.

PMID- 29047450
TI  - Quantum modeling of ultrafast photoinduced charge separation.
AB  - Phenomena involving electron transfer are ubiquitous in nature, photosynthesis
      and enzymes or protein activity being prominent examples. Their deep
      understanding thus represents a mandatory scientific goal. Moreover, controlling
      the separation of photogenerated charges is a crucial prerequisite in many
      applicative contexts, including quantum electronics, photo-electrochemical water
      splitting, photocatalytic dye degradation, and energy conversion. In particular,
      photoinduced charge separation is the pivotal step driving the storage of sun
      light into electrical or chemical energy. If properly mastered, these processes
      may also allow us to achieve a better command of information storage at the
      nanoscale, as required for the development of molecular electronics, optical
      switching, or quantum technologies, amongst others. In this Topical Review we
      survey recent progress in the understanding of ultrafast charge separation from
      photoexcited states. We report the state-of-the-art of the observation and
      theoretical description of charge separation phenomena in the ultrafast regime
      mainly focusing on molecular- and nano-sized solar energy conversion systems. In
      particular, we examine different proposed mechanisms driving ultrafast charge
      dynamics, with particular regard to the role of quantum coherence and electron
      nuclear coupling, and link experimental observations to theoretical approaches
      based either on model Hamiltonians or on first principles simulations.

PMID- 29047451
TI  - Functionalization of bacterial cellulose wound dressings with the antimicrobial
      peptide epsilon-poly-L-Lysine.
AB  - Wound dressings based on bacterial cellulose (BC) can form a soft and conformable
      protective layer that can stimulate wound healing while preventing bacteria from
      entering the wound. Bacteria already present in the wound can, however, thrive in
      the moist environment created by the BC dressing which can aggravate the healing
      process. Possibilities to render the BC antimicrobial without affecting the
      beneficial structural and mechanical properties of the material would hence be
      highly attractive. Here we present methods for functionalization of BC with
      epsilon-poly-L-Lysine (epsilon-PLL), a non-toxic biopolymer with broad-spectrum
      antimicrobial activity. Low molecular weight epsilon-PLL was cross-linked in
      pristine BC membranes and to carboxymethyl cellulose functionalized BC using
      carbodiimide chemistry. The functionalization of BC with epsilon-PLL inhibited
      growth of S. epidermidis on the membranes but did not affect the
      cytocompatibility to cultured human fibroblasts as compared to native BC. The
      functionalization had no significant effects on the nanofibrous structure and
      mechanical properties of the BC. The possibility to functionalize BC with epsilon
      PLL is a promising, green and versatile approach to improve the performance of BC
      in wound care and other biomedical applications.

PMID- 29047452
TI  - Thermal transport in epitaxial Si1-xGex alloy nanowires with varying composition
      and morphology.
AB  - We report on structural, compositional, and thermal characterization of self
      assembled in-plane epitaxial Si1-xGex alloy nanowires grown by molecular beam
      epitaxy on Si (001) substrates. The thermal properties were studied by means of
      scanning thermal microscopy, while the microstructural characteristics, the
      spatial distribution of the elemental composition of the alloy nanowires and the
      sample surface were investigated by transmission electron microscopy and energy
      dispersive x-ray microanalysis. We provide new insights regarding the morphology
      of the in-plane nanostructures, their size-dependent gradient chemical
      composition, and the formation of a 5 nm thick wetting layer on the Si substrate
      surface. In addition, we directly probe heat transfer between a heated scanning
      probe sensor and Si1-xGex alloy nanowires of different morphological
      characteristics and we quantify their thermal resistance variations. We correlate
      the variations of the thermal signal to the dependence of the heat spreading with
      the cross-sectional geometry of the nanowires using finite element method simula
      tions. With this method we determine the thermal conductivity of the nanowires
      with values in the range of 2-3 Wm-1K-1. These results provide valuable
      information in growth processes and show the great capability of the scanning
      thermal mi-croscopy technique in ambient environment for nanoscale thermal
      studies, otherwise not possible using conventional tech-niques.

PMID- 29047453
TI  - Simulation study of light transport in laser-processed LYSO:Ce detectors with
      single-side readout.
AB  - A tightly focused pulsed laser beam can locally modify the crystal structure
      inside the bulk of a scintillator. The result is incorporation of so-called
      optical barriers with a refractive index different from that of the crystal bulk,
      that can be used to redirect the scintillation light and control the light spread
      in the detector. We here systematically study the scintillation light transport
      in detectors fabricated using the laser induced optical barrier technique, and
      objectively compare their potential performance characteristics with those of the
      two mainstream detector types: monolithic and mechanically pixelated arrays.
      Among countless optical barrier patterns, we explore barriers arranged in a pixel
      like pattern extending all-the-way or half-way through a 20 mm thick LYSO:Ce
      crystal. We analyze the performance of the detectors coupled to MPPC arrays, in
      terms of light response functions, flood maps, line profiles, and light
      collection efficiency. Our results show that laser-processed detectors with both
      barrier patterns constitute a new detector category with a behavior between that
      of the two standard detector types. Results show that when the barrier-crystal
      interface is smooth, no DOI information can be obtained regardless of barrier
      refractive index (RI). However, with a rough barrier-crystal interface we can
      extract multiple levels of DOI. Lower barrier RI results in larger light
      confinement, leading to better transverse resolution. Furthermore we see that the
      laser-processed crystals have the potential to increase the light collection
      efficiency, which could lead to improved energy resolution and potentially better
      timing resolution due to higher signals. For a laser-processed detector with
      smooth barrier-crystal interfaces the light collection efficiency is simulated to
      >42%, and for rough interfaces  >73%. The corresponding numbers for a monolithic
      crystal is 39% with polished surfaces, and 71% with rough surfaces, and for a
      mechanically pixelated array 35% with polished pixel surfaces and 59% with rough
      surfaces.

PMID- 29047454
TI  - Analysis of dose heterogeneity using a subvolume-DVH.
AB  - The dose-volume histogram (DVH) is universally used in radiation therapy for its
      highly efficient way of summarizing three-dimensional dose distributions. An
      apparent limitation that is inherent to standard histograms is the loss of
      spatial information, e.g. it is no longer possible to tell where low- and high
      dose regions are, and whether they are connected or disjoint. Two methods for
      overcoming the spatial fragmentation of low- and high-dose regions are presented,
      both based on the gray-level size zone matrix, which is a two-dimensional
      histogram describing the frequencies of connected regions of similar intensities.
      The first approach is a quantitative metric which can be likened to a homogeneity
      index. The large cold spot metric (LCS) is here defined to emphasize large
      contiguous regions receiving too low a dose; emphasis is put on both size, and
      deviation from the prescribed dose. In contrast, the subvolume-DVH (sDVH) is an
      extension to the standard DVH and allows for a qualitative evaluation of the
      degree of dose heterogeneity. The information retained from the two-dimensional
      histogram is overlaid on top of the DVH and the two are presented simultaneously.
      Both methods gauge the underlying heterogeneity in ways that the DVH alone
      cannot, and both have their own merits-the sDVH being more intuitive and the LCS
      being quantitative.

PMID- 29047455
TI  - A Monte-Carlo study to assess the effect of 1.5 T magnetic fields on the overall
      robustness of pencil-beam scanning proton radiotherapy plans for prostate cancer.
AB  - Combining magnetic-resonance imaging (MRI) and proton therapy (PT) using pencil
      beam scanning (PBS) may improve image-guided radiotherapy. We aimed at assessing
      the impact of a magnetic field on PBS-PT plan quality and robustness.
      Specifically, the robustness against anatomical changes and positioning errors in
      an MRI-guided scenario with a 30 cm radius 1.5 T magnetic field was studied for
      prostate PT. Five prostate cancer patients with three consecutive CT images (CT1
      3) were considered. Single-field uniform dose PBS-PT plans were generated on the
      segmented CT1 with Monte-Carlo-based treatment planning software for inverse
      optimization. Plans were optimized at 90 degrees  gantry angle without B-field
      (no B), with  +/-1.5 T B-field (B and minus B), as well as at 81 degrees  gantry
      angle and  +1.5 T (B G81). Plans were re-calculated on aligned CT2 and CT3 to
      study the impact of anatomical changes. Dose distributions were compared in terms
      of changes in DVH parameters, proton range and gamma-index pass-rates. To assess
      the impact of positioning errors, DVH parameters were compared for  +/-5 mm CT1
      patient shifts in anterior-posterior (AP) and left-right (LR) direction. Proton
      beam deflection considerably reduced robustness against inter-fractional changes
      for the B scenario. Range agreement, gamma-index pass-rates and PTV V95% were
      significantly lower compared to no B. Improved robustness was obtained for minus
      B and B G81, the latter showing only minor differences to no B. The magnetic
      field introduced slight dosimetric changes under LR shifts. The impact of AP
      shifts was considerably larger, and equivalent for scenarios with and without B
      field. Results suggest that robustness equivalent to PT without magnetic field
      can be achieved by adaptation of the treatment parameters, such as B-field
      orientation (minus B) with respect to the patient and/or gantry angle (B G81).
      MRI-guided PT for prostate cancer might thus be implemented without compromising
      robustness compared to state-of-the-art CT-guided PT.

PMID- 29047456
TI  - A reusable OSL-film for 2D radiotherapy dosimetry.
AB  - Optical stimulated luminescence (OSL) combines reusability, sub-mm resolution,
      and a linear dose response in a single radiation detection technology. Such a
      combination is currently lacking in radiotherapy dosimetry. But OSL-films have a
      strong energy dependent response to keV photons due to a relative high effective
      atomic number (Z eff). The current work studied the applicability of a 2D OSL
      film with a reduced Z eff as (IMRT/VMAT) dosimeter. Based on their commercial OSL
      film experience, Agfa Healthcare N.V. produced a new experimental OSL-film for RT
      dosimetry. This film had a lower effective atomic number compared to the films
      used in radiology. Typical 2D dosimeter requirements such as uniformity, dose
      response, signal stability with time, and angular dependence were evaluated.
      Additionally, the impact of a possible residual energy dependence was assessed
      for the infield as well as the out-of-field region of both static beams and
      standard intensity modulated patterns (chair and pyramid). The OSL-film's
      reusable nature allowed for a film specific absolute and linear calibration
      including a flood-field uniformity correction. The OSL-film was scanned with a CR
      15X engine based reader using a strict timing (i.e. 4 min after 'beam on' or as
      soon as possible) to account for spontaneous recombination. The OSL-film had good
      basic response properties: non-uniformities  ?2.6%, a linear dose response (0-32
      Gy), a linear signal decay (0.5% min-1) over the 20 min measured, and limited
      angular dependence  ?2.6%. Due to variations of the energy spectrum, larger dose
      differences were noted outside the central region of the homogenous phantom and
      outside both static and IMRT fields. However, the OSL-film's measured dose
      differences of the IMRT patterns were lower than those of Gafchromic EBT
      measurements ([-1.6%, 2.1%] versus [-2.9%, 3.6%]). The current OSL-film could be
      used as a reusable high resolution dosimeter with read-out immediately after
      irradiation. Inside the (IMRT) treatment fields residual energy dependent effects
      were not observed. Novelty and significance: Implementing a reusable optical
      stimulated luminescence (OSL) film for radiotherapy dosimetry would enable user
      friendly, sub(mm) resolution 2D dosimetry with instantaneous read-out. Radiology
      OSL-films have a strong energy dependent response which hampers accurate
      dosimetry. The current work reports measurements with a first 2D OSL-film
      tailored to the radiotherapy needs: including an improved water equivalent
      composition. The dosimeter adds the ability for sub-mm resolution repeated
      measurements to the portfolio of radiotherapy dosimetry.

PMID- 29047457
TI  - Effects of penile fracture and its surgical treatment on psychosocial and sexual
      function.
AB  - The current therapy for penile fracture is immediate surgical repair, but sexual
      and psychosocial effects of the repair have been poorly investigated. We aimed to
      assess the impact of surgical correction of penile fracture on psychosocial
      status, sexual function, and erectile quality. Sixty-four patients classified
      into two subgroups according to follow-up: 2-24 months (Group 1), and longer than
      24 months (Group 2), and 28 healthy men (Control group). The mean overall follow
      up period was 39.1+/-32.7 months. The number of sexual intercourse origin was 44
      (68.8%), the mean time interval from incident-to-surgery was 13.6+/-9.3 h. The
      mean sexual relationship score decreased during first year (P=0.001), and
      significant recovery was observed over 12-24 months. The mean overall
      relationship scores and the mean self-esteem scores of the study groups decreased
      until the end of the 24 months (P<0.05). The mean erectile function domains
      remained stable in all groups (P>0.05). The mean EHS scores were lower but the
      difference was not significant in the study groups (P>0.05). Penile fracture
      repair have no detrimental effect on sexual function, but psychogenic aspect may
      be adversely affected. This article concludes lower complication rates can be
      reached with immediate surgical correction of the penile fracture whereas
      psychogenic recovery might prolonged.

PMID- 29047458
TI  - Recordings of Caenorhabditis elegans locomotor behaviour following targeted
      ablation of single motorneurons.
AB  - Lesioning studies have provided important insight into the functions of brain
      regions in humans and other animals. In the nematode Caenorhabditis elegans, with
      a small nervous system of 302 identified neurons, it is possible to generate
      lesions with single cell resolution and infer the roles of individual neurons in
      behaviour. Here we present a dataset of ~300 video recordings representing the
      locomotor behaviour of animals carrying single-cell ablations of 5 different
      motorneurons. Each file includes a raw video of approximately 27,000 frames; each
      frame has also been segmented to yield the position, contour, and body curvature
      of the tracked animal. These recordings can be further analysed using publicly
      available software to extract features relevant to behavioural phenotypes. This
      dataset therefore represents a useful resource for probing the neural basis of
      behaviour in C. elegans, a resource we hope to augment in the future with
      ablation recordings for additional neurons.

PMID- 29047459
TI  - Protostemonine effectively attenuates lipopolysaccharide-induced acute lung
      injury in mice.
AB  - Protostemonine (PSN) is the main anti-inflammatory alkaloid extracted from the
      roots of Stemona sessilifolia (known as "Baibu" in traditional Chinese medicine).
      Here, we reported the inhibitory effects of PSN on lipopolysaccharide (LPS)
      induced macrophage activation in vitro and LPS-induced acute lung injury in mice.
      Macrophage cell line RAW264.7 cells and mouse bone marrow-derived macrophages
      (BMDMs) were treated with PSN (1, 3, 10, 30 and 100 MUmol/L) for 0.5 h and then
      challenged with LPS (0.1 MUg/mL) for 24 h. Pretreatment with PSN significantly
      inhibited LPS-induced phosphorylation of MAPKs and AKT, iNOS expression and NO
      production in the macrophages. C57BL/6 mice were intratracheally injected with
      LPS (5 mg/kg) to induce acute lung injury (ALI). The mice were subsequently
      treated with PSN (10 mg/kg, ip) at 4 and 24 h after LPS challenge. PSN
      administration significantly attenuated LPS-induced inflammatory cell
      infiltration, reduced pro-inflammatory cytokine (TNF-alpha, IL-1beta and IL-6)
      production and eliminated LPS-mediated lung edema. Furthermore, PSN
      administration significantly inhibited LPS-induced pulmonary MPO activity.
      Meanwhile, LPS-induced phosphorylation of p38 MAPK, iNOS expression and NO
      production in the lungs were also suppressed. The results demonstrate that PSN
      effectively attenuates LPS-induced inflammatory responses in vitro and in vivo;
      the beneficial effects are associated with the decreased phosphorylation of MAPK
      and AKT and the reduced expression of pro-inflammatory mediators, such as iNOS,
      NO and cytokines. These data suggest that PSN may be a potential therapeutic
      agent in the treatment of ALI.

PMID- 29047462
TI  - Icebows.
AB  - Theoretical and experimental studies show that water ice spheres can produce a
      rainbow in which the primary and secondary bows overlap. To our knowledge, no
      such natural "icebow" has ever been reported.

PMID- 29047463
TI  - Simultaneous observation of a glory and in-situ microphysical cloud properties.
AB  - While making airborne measurements of cloud particles, a bright glory was
      observed on a thin layer cloud. By deliberately flying through this glory
      producing cloud on several occasions, cloud particle size distributions were
      obtained. We found that warm liquid clouds with narrow cloud droplet size
      distributions are responsible for producing the observed glory. This paper
      presents these results and compares the results of Mie theory simulations with an
      image of the glory.

PMID- 29047464
TI  - Iridescent clouds and distorted coronas.
AB  - Near-forward scattering of sunlight generates coronas and iridescence on clouds.
      Coronas are caused by diffraction, whereas iridescence is less easily explained.
      Iridescence often appears as bands of color aligned with the edges of clouds or
      as apparently random patches of color on clouds. This paper suggests that
      iridescence is due to interference between light that has been diffracted by a
      spherical droplet of water and light that has been transmitted through the same
      droplet.

PMID- 29047460
TI  - Computational insights into the subtype selectivity and "message-address
      efficacy" mechanisms of opioid receptors through JDTic binding and unbinding.
AB  - In drug design and discovery, binding affinity and selectivity are two basic
      properties of a drug candidate. Opioid receptors (ORs) are the main targets of
      strong analgesics. Like some other class A members of G-protein-coupled receptors
      (GPCRs), ORs exhibit complex selectivity on their ligands. The diversity of
      binding activity and selectivity among opioids has deeply attracted researchers
      for a long time. To investigate the subtype selectivity of MU, delta and kappa
      ORs in detail, using the kappa-selective antagonist JDTic as a probe, we
      performed a series of computational simulations, including molecular dynamics and
      metadynamics, on JDTic-MU/delta/kappa-OR complexes. From the simulations, we
      found that the decisive factor of JDTic selectivity on the MU-subtype was the
      2.63 position, which affected the efficacy of JDTic through changing the dynamics
      of the Q2.60 residue. In addition to the 2.63-position residue, the 7.35 position
      was the other crucial aspect of JDTic selectivity for the delta-subtype. Based on
      the results, we suggest a new concept, the "message-address-efficacy" hypothesis,
      to explain the relationships among the affinity, selectivity and function between
      ORs and opioids. Thus, all the detailed dynamics of JDTic-bound ORs might be
      helpful to deeply understand the subtype selectivity and binding mechanisms of
      other GPCRs.

PMID- 29047465
TI  - Transmission bows of radially inhomogeneous spheres.
AB  - We consider transmission scattering of a plane wave by a radially inhomogeneous
      sphere containing a localized region of refractive index decrease. In ray theory,
      the boundary conditions on the deflection angle at axial and grazing incidence
      determine that transmission scattering gives rise to an even number of bows, half
      of them being relative maximum bows and half being relative minimum bows. For a
      model refractive index profile, we determine the conditions under which different
      numbers of bows occur, and we suggest physical mechanisms responsible for
      producing them. We also verify that these bows occur in wave scattering in the
      short wavelength limit, both in the frequency domain and time domain.

PMID- 29047461
TI  - Hematopoietic stem cell-derived exosomes promote hematopoietic differentiation of
      mouse embryonic stem cells in vitro via inhibiting the miR126/Notch1 pathway.
AB  - Cell-derived exosomes (EXs) can modulate target cell differentiation via
      microRNAs (miRs) that they carried. Previous studies have shown that miR126 is
      highly expressed in hematopoietic stem cells (HSCs) and plays a role in
      hematopoiesis via modulating the Notch pathway that participates in progenitors'
      cell fate decisions. In this study we investigated whether HSC-derived EXs (HSC
      EXs) could affect the differentiation of mouse embryonic stem cells (ESCs) into
      HSCs. We prepared HSC-EXscon, HSC-EXssc and HSC-EXsmiR126 from control HSCs and
      the HSCs transfected with scramble control or miR126 mimics, respectively. HSC
      EXs were isolated by ultracentrifugation and analyzed using nanoparticle tracking
      analysis. We incubated the collected EXs with mouse ESCs over a 10-d
      differentiation induction period, during which HSC-EXs and a Notch pathway
      activator (Jagged1, 100 ng/mL) were added to the cultures every 3 d. After the 10
      d differentiation period, the expression levels of miR126, SSEA1, CD117, Sca1,
      Notch1 and Hes1 in ESCs were assessed. The generated HSCs were validated by flow
      cytometry using antibodies against HSC markers (CD117, CD34 and Sca1). Our
      results revealed that: (1) transfection with miR126 mimics significantly
      increased miR126 levels in HSC-EXsmiR126. (2) HSC-EX co-culture promoted mouse
      ESCs differentiation into HSCs with the most prominent effect found in the HSC
      EXsmiR126 co-culture. (3) HSC differentiation was verified by reduced SSEA1
      expression and increased CD117 and Sca1 expression. (4) All the effects caused by
      HSC-EXs were accompanied by significant reduction of Notch1 and Hes1 expression,
      thus inhibition of the Notch1/Hes1 pathway, whereas activation of Notch by
      Jagged1 abolished the effects of HSC-EXsmiR126. In conclusion, HSC-EXs promote
      hematopoietic differentiation of mouse ESCs in vitro by inhibiting the
      miR126/Notch1 pathway.

PMID- 29047466
TI  - Mountain shadows revisited.
AB  - Using purely geometric considerations, a sequence of mountain shadow models is
      considered. The observer is located at the summit of idealized mountains with
      several different cross-sectional profiles. The result for a triangular profile
      is generalized to the case of an off-summit observer. We also examine the case of
      a conical mountain. In addition, a simple geometric model is formulated for
      mountain "spikes" in terms of the differences in shadow length and contrast for
      an off-summit observer within the shadow. The first appendix is devoted to the
      notion of "umbral volume" and the second to the geometry of sunlit areas on a
      conical mountain.

PMID- 29047467
TI  - Blue sun glints on water viewed through a polarizer.
AB  - Sun glints are formed by specular reflections of the sun from capillary waves
      formed by wind blowing over water. These glints are normally colorless for a high
      sun or take on the color of the light source, such as orange-red during sunset or
      sunrise. However, when the glints are highly polarized by reflection near the
      Brewster angle, i.e., with relatively high sun they can change from colorless to
      a blue appearance caused by blue light leakage through a polarizing filter
      oriented orthogonal to the plane of polarization of the reflected light.
      Measurements are shown of crossed-polarizer transmission spectra exhibiting blue
      and near infrared light leakage for photographic polarizing filters and polarized
      sunglasses. A variety of photographs is shown to confirm blue light leakage as
      the source of the blue glint color.

PMID- 29047468
TI  - Spectral measurement and modeling of natural rainbows.
AB  - Although quantitative observations of rainbow spectra, colors, and luminances are
      needed for any comprehensive analysis of rainbow scattering theory, very little
      such data has been published. But new remote sensing tools now make possible the
      detailed spectral and colorimetric measurement of natural rainbows, which here
      are defined as bows seen in sunlit rain or water-drop sprays. To measure these
      often short-lived phenomena, both multispectral tools (colorimetrically
      calibrated RGB cameras) and hyperspectral tools (imaging spectrometers) are used
      to examine the spectral and angular fine structure of natural rainbows. Airy
      theory for aerodynamically flattened drops helps to explain some of these bows'
      observed features, such as the reduced color gamuts caused by smaller drop sizes
      and low sun elevations h0. However, other features such as the distinct blues
      seen in rainbows at higher h0 are not well explained.

PMID- 29047469
TI  - Mirages at Lake Geneva: the Fata Morgana.
AB  - Fata Morgana mirages are frequently seen at Lake Geneva. We show the first
      photographs of them, including a real-time video, and explain their main
      features, which are due to the very turbulent entrainment zones of capping
      inversions, especially in valley circulations.

PMID- 29047470
TI  - Hafgerdingar and giant waves.
AB  - A 13th-century text in Old Norse, Konungs Skuggsja (translated as The King's
      Mirror), tells about a phenomenon that may be encountered in the Greenland Sea.
      It is called hafgerdingar (sea fences). The horizon is raised, and from there
      three giant waves come rolling in. Recently Lehn and Schroeder have explained the
      phenomenon as a superior mirage. I extend their analysis by introducing a
      periodic time dependence in the properties of the inversion layer, and show that
      also the illusion of incoming waves and an immediate danger may so be explained.

PMID- 29047471
TI  - Teaching rainbows with simulations: revisiting Minnaert's lab experiment.
AB  - This work presents an educational simulation to support students' learning about
      the formation of the rainbow. The main aim of the simulation is to provide our
      students with a didactic tool in addition to their traditional laboratory
      practice, which can be easily implemented in e-learning teaching platforms. A
      system consisting of a flask filled with water and a screen with a rounded
      aperture placed between the sun and the flask was simulated; this way a faint
      rainbow was seen on the simulated screen. The interactive nature of the
      simulation allowed the students to perform some alterations that would be
      impossible to do in the real world; thus, the observed rainbow deviated from the
      simplest model. Additionally, all these modifications could be rendered into an
      animation, in order to observe changes in real time.

PMID- 29047472
TI  - High-order rainbows of a spherical particle produced by near-grazing incident
      light.
AB  - This study is concerned with the formation of high-order rainbows by near-grazing
      light incident on a spherical particle. As the number of internal reflections
      involved increases, the incident Descartes ray strikes the sphere surface
      increasingly closer to its edge, where the predictions of ray theory and Airy
      theory become invalid. The deflection angle of the confluence of the stationary
      points of the phase of the partial wave scattering amplitudes is studied as a
      function of rainbow order and sphere radius. It is found that as the rainbow
      order increases, the angular interval over which the upper supernumerary ray
      stationary point occurs shrinks to zero. In addition, for deflection angles
      beyond the confluence of the upper supernumerary ray with the tunneling ray,
      intensity oscillations are due to interference of the field of the lower
      supernumerary ray with that of the edge region Fock transition, rather than
      interference between the upper and lower supernumerary rays.

PMID- 29047473
TI  - Supernumerary arcs of rainbows: Young's theory of interference.
AB  - Supernumerary arcs on rainbows are historically important because in the early
      1800s they provided evidence in favor of the wave theory of light. The success of
      Airy's rainbow integral has overshadowed the earlier contribution from Young, who
      proposed that supernumerary arcs were caused by interference between two
      geometrical rays that emerge from the raindrop at the same scattering angle. Airy
      dismissed Young's idea as "the imperfect theory of interference" because it
      predicted supernumerary arcs at the wrong angles. Young was unaware that a light
      ray encountering a focal line can suffer a phase shift of 90 degrees . If these
      phase shifts are taken into account, the theory of interference becomes
      surprisingly accurate.

PMID- 29047474
TI  - Rainbows by elliptically deformed drops. I. Mobius shift for high-order rainbows.
AB  - Using ray theory, the Mobius shift of the (p-1)-order rainbow angle for a
      particle having an elliptical cross section is obtained to first order in the
      ellipticity as a function of the tilt of the ellipse with respect to the
      propagation direction of the incoming rays. The result is then adapted to the
      geometry of scattering of light rays from the sun by a falling water drop as a
      function of sun height angle. The variation in the angular spacing between the
      supernumeraries is determined as a function of location along the rainbow arc,
      the conditions under which the rainbow angle is insensitive to drop flattening
      were determined, and the dependence of the Mobius shift on the drop refractive
      index is shown for rainbows up to fourth order (p=5).

PMID- 29047475
TI  - Rainbows by elliptically deformed drops. II. The appearance of supernumeraries of
      high-order rainbows in rain showers.
AB  - The appearance of supernumeraries of high-order rainbows in heavy rain showers is
      explored for rainbows up to order five (p=6). This is done by using a combination
      of the ray-theory-based first-order Mobius approximation for high-order rainbows
      with the Airy approximation of the rainbow radiance distribution. We conclude
      that supernumerary formation of rainbows of order three, four, and five is
      possible in natural rain showers. Supernumeraries of the third-order and fourth
      order rainbows are preferentially formed near the bottom of these rainbows. A
      strategy for observing supernumeraries of high-order rainbows is proposed.

PMID- 29047476
TI  - Inflight observation of Bottlinger's rings.
AB  - On the morning of 5 November 2013, a bright subsun was consistently visible
      during a flight from Bozeman, Montana, to Salt Lake City, Utah. Just after
      passing over the Wasatch Mountains and beginning to descend into the Salt Lake
      Valley, the subsun expanded to a rare display of Bottlinger's rings-an elliptical
      halo surrounding the subsun. The rings remained visible for 1 to 2 min. This
      paper shows photographs of the sequence, along with meteorological data from a
      nearby radiosonde. The display occurred in virga below clouds at an air
      temperature in the approximate range from -8 degrees C to -12 degrees C, in air
      saturated with respect to ice, at an altitude of approximately 2600-3600 m above
      mean sea level.

PMID- 29047477
TI  - How daylight influences high-order chromatic descriptors in natural images.
AB  - Despite the global and local daylight changes naturally occurring in natural
      scenes, the human visual system usually adapts quite well to those changes,
      developing a stable color perception. Nevertheless, the influence of daylight in
      modeling natural image statistics is not fully understood and has received little
      attention. The aim of this work was to analyze the influence of daylight changes
      in different high-order chromatic descriptors (i.e., color volume, color gamut,
      and number of discernible colors) derived from 350 color images, which were
      rendered under 108 natural illuminants with Correlated Color Temperatures (CCT)
      from 2735 to 25,889 K. Results suggest that chromatic and luminance information
      is almost constant and does not depend on the CCT of the illuminant for values
      above 14,000 K. Nevertheless, differences between the red-green and blue-yellow
      image components were found below that CCT, with most of the statistical
      descriptors analyzed showing local extremes in the range 2950 K-6300 K. Uniform
      regions and areas of the images attracting observers' attention were also
      considered in this analysis and were characterized by their patchiness index and
      their saliency maps. Meanwhile, the results of the patchiness index do not show a
      clear dependence on CCT, and it is remarkable that a significant reduction in the
      number of discernible colors (58% on average) was found when the images were
      masked with their corresponding saliency maps. Our results suggest that chromatic
      diversity, as defined in terms of the discernible colors, can be strongly reduced
      when an observer scans a natural scene. These findings support the idea that a
      reduction in the number of discernible colors will guide visual saliency and
      attention. Whatever the modeling is mediating the neural representation of
      natural images, natural image statistics, it is clear that natural image
      statistics should take into account those local maxima and minima depending on
      the daylight illumination and the reduction of the number of discernible colors
      when salient regions are considered.

PMID- 29047478
TI  - Colored thunderstorms.
AB  - Three scenarios that produce colored thunderstorms are simulated. In Scenario #1,
      the thunderstorm's sunlit face exhibits a color gradient from white or yellow at
      top to red at base when the sun is near the horizon. It is simulated with a
      second-order scattering model as a combination of sunlight and skylight reflected
      from the cloud face that is attenuated and reddened by Rayleigh and Mie
      scattering over the long optical path near sunset that increases from cloud top
      to base. In Scenario #2, the base of the precipitation shaft appears luminous
      green-blue when surrounded by a much darker arcus cloud. It is simulated as
      multiply scattered light transmitted through the precipitation shaft using a
      Monte Carlo model that includes absorption by liquid water and ice. The color
      occurs over a wide range of solar zenith angles with large liquid water content,
      but the precipitation shaft is only bright when hydrometeors are large.
      Attenuation of the light by Rayleigh and Mie scattering outside the precipitation
      shaft shifts the spectrum to green when viewed from a distance of several
      kilometers. In Scenario #3, the shaded cloud face exhibits a "sickly" yellow
      green color. It is simulated with a second-order scattering model as the result
      of distant skylight that originates in the sunlit region beyond an opaque anvil
      of order 40 km wide but is attenuated by Rayleigh and Mie scattering in its path
      to the cloud and observer.

PMID- 29047479
TI  - Light scattering from sessile water drops and raindrop-shaped glass beads as a
      validation tool for rainbow simulations.
AB  - The shape deviation of falling raindrops from exact spheres is known to affect
      the appearance of natural rainbows, e.g., by enhancing the visibility of
      supernumerary arcs around the top or by creating branching effects known as
      "twinned rainbows." To check the accuracy of numerical optical models for rainbow
      scattering from such nonspherical drops, two simple and low-cost experiments are
      presented in this paper: (1) sessile, i.e., sitting, drops on ultrahydrophobic
      surfaces, and (2) glass beads in the shape of falling raindrops. The experimental
      results are compared to polarization-resolved Monte Carlo ray-tracing
      simulations, with special emphasis on circular polarization, which results from
      total internal reflections in these nonspherical scatterers.

PMID- 29047480
TI  - Atmospheric optics in the near infrared.
AB  - Digital near-infrared photography opens up new observation possibilities and
      applications for atmospheric optics. We discuss necessary conditions and
      requirements for observing a variety of atmospheric optical phenomena in the
      infrared spectral range and report for the first time near-infrared photographs
      of 22 degrees  ring halos and inferior mirages. Our emphasis is on optical
      phenomena observable in the troposphere, excluding the large body of work
      addressing near-infrared airglow and aurora.

PMID- 29047481
TI  - Antitwilight II: Monte Carlo simulations.
AB  - For this paper, we employ the Monte Carlo scene (MCScene) radiative transfer code
      to elucidate the underlying physics giving rise to the structure and colors of
      the antitwilight, i.e., twilight opposite the Sun. MCScene calculations
      successfully reproduce colors and spatial features observed in videos and still
      photos of the antitwilight taken under clear, aerosol-free sky conditions.
      Through simulations, we examine the effects of solar elevation angle, Rayleigh
      scattering, molecular absorption, aerosol scattering, multiple scattering, and
      surface reflectance on the appearance of the antitwilight. We also compare
      MCScene calculations with predictions made by the MODTRAN radiative transfer code
      for a solar elevation angle of +1 degrees .

PMID- 29047482
TI  - Tropospheric haze and colors of the clear twilight sky.
AB  - At the earth's surface, clear-sky colors during civil twilights depend on the
      combined spectral effects of molecular scattering, extinction by tropospheric
      aerosols, and absorption by ozone. Molecular scattering alone cannot produce the
      most vivid twilight colors near the solar horizon, for which aerosol scattering
      and absorption are also required. However, less well known are haze aerosols'
      effects on twilight sky colors at larger scattering angles, including near the
      antisolar horizon. To analyze this range of colors, we compare 3D Monte Carlo
      simulations of skylight spectra with hyperspectral measurements of clear twilight
      skies over a wide range of aerosol optical depths. Our combined measurements and
      simulations indicate that (a) the purest antisolar twilight colors would occur in
      a purely molecular, multiple-scattering atmosphere, whereas (b) the most vivid
      solar-sky colors require at least some turbidity. Taken together, these results
      suggest that multiple scattering plays an important role in determining the
      redness of the antitwilight arch.

PMID- 29047483
TI  - Antitwilight I: structure and optics.
AB  - Time-lapse videos, still photos, visual observations, and theoretical studies
      were used to investigate the antitwilight, i.e., twilight opposite the Sun.
      Colors, brightnesses, and antitwilight features as a function of solar altitude
      were measured. Four roughly horizontal bands were identified and explained
      physically in terms of atmospheric geometry, the observer's line-of-sight,
      optical depth, refraction, and multiple scattering. Particular emphasis is placed
      on (1) the origin of the dark segment, (2) the rapid rising of the Belt of Venus
      with solar altitude, and (3) ray tracing light through the low atmosphere to
      understand refractive effects. New names are suggested for three of the four
      bands, and the new terminology is reconciled with earlier papers.

PMID- 29047484
TI  - Characterizing ice particles using two-dimensional reflections of a lidar beam.
AB  - We report a phenomenon manifesting itself as brief flashes of light on the snow's
      surface near a lidar beam. The flashes are imaged and interpreted as specular
      reflection patterns from individual ice particles. Such patterns have a two
      dimensional structure and are similar to those previously observed in forward
      scattering. Patterns are easiest to capture from particles with well-defined
      horizontal facets, such as near-horizontally aligned plates. The patterns and
      their position can be used to determine properties such as ice particle shape,
      size, roughness, alignment, and altitude. Data obtained at Summit in Greenland
      show the presence of regular hexagonal and scalene plates, columns, and rounded
      plates of various sizes, among others.

PMID- 29047485
TI  - Terahertz bistability and multistability in graphene/dielectric Fibonacci
      multilayer.
AB  - Here, we benefit from the strong nonlinear response of graphene and the rich
      variety of resonances provided by a graphene/dielectric Fibonacci multilayer to
      realize bistability and multistability in the terahertz (THz) frequency range.
      Toward this pursuit, we employ the nonlinear transfer matrix method. We examine
      the suitability of resonances in the Fibonacci multilayer for the
      bi/multistability purposes and determine the proper working point. We report
      various switching up/down manners via single or stepwise jumps between states of
      the same or different contrasts upon increasing followed by decreasing the
      intensity of the incident wave. We show that graphene samples of high quality are
      preferred for bi/multistable switching in terms of reducing the switch-up/-down
      thresholds and widening the multistable region. We also explore the possibility
      of tuning the bi/multistable behavior via the frequency and angle of the incident
      wave as well as the graphene Fermi level. We envision precious applications in
      THz switching, realizing logic gates, and so on for this system.

PMID- 29047486
TI  - Scattering of aerosol particles by a Hermite-Gaussian beam in marine atmosphere.
AB  - Based on the complex-source-point method and the generalized Lorenz-Mie theory,
      the scattering properties and polarization of aerosol particles by a Hermite
      Gaussian (HG) beam in marine atmosphere is investigated. The influences of beam
      mode, beam width, and humidity on the scattered field are analyzed numerically.
      Results indicate that when the number of HG beam modes u (v) increase, the radar
      cross section of aerosol particles alternating appears at maximum and minimum
      values in the forward and backward scattering, respectively, because of the
      special petal-shaped distribution of the HG beam. The forward and backward
      scattering of aerosol particles decreases with the increase in beam waist. When
      beam waist is less than the radius of the aerosol particle, a minimum value is
      observed in the forward direction. The scattering properties of aerosol particles
      by the HG beam are more sensitive to the change in relative humidity compared
      with those by the plane wave and the Gaussian beam (GB). The HG beam shows
      superiority over the plane wave and the GB in detecting changes in the relative
      humidity of marine atmosphere aerosol. The effects of relative humidity on the
      polarization of the HG beam have been numerically analyzed in detail.

PMID- 29047487
TI  - 10.23  Mcps laser pseudo-code ranging system with 0.33  mm (1sigma) pseudo-range
      measurement precision.
AB  - The inter-satellite laser link is the backbone of the next inter-satellite
      information network, and ranging and communication are the main functions of the
      inter-satellite laser link. This study focuses on the inter-satellite laser
      ranging based on the pseudo-code correlation technology. In this paper, several
      typical laser-ranging methods have been compared and we determined that the laser
      pseudo-code ranging architecture is more suitable for the inter-satellite laser
      communication link. The pseudo-code ranging system is easy to combine with a
      digital communication system, and we used it to calculate integer ambiguity by
      modulating the time information. The main challenge of the ranging system is
      range precision, which is the main focus of this paper. First, the framework of
      the pseudo-code ranging system is introduced; the ranging architecture of dual
      one-way ranging is used to eliminate the clock error between the two
      transceivers, and then the uncertainty of the phase detector is analyzed. In the
      analysis, the carrier to noise ratio and the ranging code rate are constrained by
      the laser communication link margin and the electronic hardware limitation.
      Therefore, the relationship between the sampling depth and the phase detector
      uncertainty is verified. A series of optical fiber channel laser pseudo-code
      ranging experiments demonstrated the effects of sampling depth on the ranging
      precision. By adjusting the depth of storage, such as the depth of 1.6 Mb, we
      obtained a pseudo-range measurement precision of 0.33 mm (1sigma), which is
      equivalent to 0.0001 times code subdivision of 10.23 Mcps pseudo-code. This paper
      has achieved high precision in a pseudo-range measurements, which is the
      foundation of the inter-satellite laser link.

PMID- 29047488
TI  - Composite reflective/absorptive IR-blocking filters embedded in metamaterial
      antireflection-coated silicon.
AB  - Infrared (IR)-blocking filters are crucial for controlling the radiative loading
      on cryogenic systems and for optimizing the sensitivity of bolometric detectors
      in the far-IR. We present a new IR filter approach based on a combination of
      patterned frequency-selective structures on silicon and a thin (25-75 MUm thick)
      absorptive composite based on powdered reststrahlen absorbing materials. For a
      300 K blackbody, this combination reflects ~50% of the incoming light and blocks
      >99.8% of the total power with negligible thermal gradients and excellent low
      frequency transmission. This allows a reduction in the IR thermal loading to
      negligible levels in a single cold filter. These composite filters are fabricated
      on silicon substrates, which provide excellent thermal transport laterally
      through the filter and ensure that the entire area of the absorptive filter stays
      near the bath temperature. A metamaterial antireflection coating cut into these
      substrates reduces in-band reflections to below 1%, and the in-band absorption of
      the powder mix is below 1% for signal bands below 750 GHz. This type of filter
      can be directly incorporated into silicon refractive optical elements.

PMID- 29047489
TI  - Grating- and checkerboard-based zone plates as an optical array generator with a
      favorable beam shape.
AB  - The combination of a grating as a periodic object and a Fresnel zone plate with a
      quasi-periodic structure leads us to propose some novel array generator elements.
      It is shown that diffraction performance of the proposed element depends on the
      grating structure, so that the diffraction performance may efficiently be
      increased if the grating is replaced with a checkerboard structure. Depending on
      the kind of zone plate, we have demonstrated that the corresponding array
      generator is also created. For instance, a focused array of vortices is generated
      when the zone plate is replaced with a spiral zone plate. We have also clarified
      that the method allows us to generalize it to the other class of the zone plate
      based elements, e.g., a cross zone plate. Namely, when the cross zone plate is
      used instead of the Fresnel zone plate, a spot array generator is again created
      whose diffractive performance is improved by modifying its phase structure. Also,
      it is clearly shown that the focusing feature of the element depends on the
      grating period. Finally, there is a good agreement between the simulation results
      and the corresponding experimental works.

PMID- 29047490
TI  - Lp-norm-residual constrained regularization model for estimation of particle size
      distribution in dynamic light scattering.
AB  - In particle size measurement using dynamic light scattering (DLS), noise makes
      the estimation of the particle size distribution (PSD) from the autocorrelation
      function data unreliable, and a regularization technique is usually required to
      estimate a reasonable PSD. In this paper, we propose an Lp-norm-residual
      constrained regularization model for the estimation of the PSD from DLS data
      based on the Lp norm of the fitting residual. Our model is a generalization of
      the existing, commonly used L2-norm-residual-based regularization methods such as
      CONTIN and constrained Tikhonov regularization. The estimation of PSDs by the
      proposed model, using different Lp norms of the fitting residual for p=1, 2, 10,
      and infinity, is studied and their performance is determined using simulated and
      experimental data. Results show that our proposed model with p=1 is less
      sensitive to noise and improves stability and accuracy in the estimation of PSDs
      for unimodal and bimodal systems. The model with p=1 is particularly applicable
      to the noisy or bimodal PSD cases.

PMID- 29047491
TI  - 40  GHz narrow linewidth frequency-switched microwave signal generation based on
      a single-longitudinal-mode double-Brillouin-frequency spaced Brillouin fiber
      laser.
AB  - A novel approach to generating 40 GHz narrow linewidth frequency-switched
      microwave signals is proposed and demonstrated. In this scheme, a single
      longitudinal-mode (SLM) double-Brillouin-frequency spaced Brillouin fiber laser
      with dual-ring configuration and unpumped erbium-doped fiber (EDF) is used to
      generate dual-wavelength lasers, and a fiber Bragg grating is used to select the
      laser for different Brillouin frequency spacings. Dual-ring configuration and
      unpumped EDF are designed to select the mode for the SLM laser. Dual-wavelength
      lasers are inserted into a photodetector, and microwave signals at 10.66, 21.39,
      32.12, or 42.85 GHz can be obtained. The linewidth of the generated microwave
      signals is less than 69 kHz. The frequency drift at each frequency is less than
      0.83 MHz. The frequency noise and linewidth of Stokes signals are measured, and
      the linewidth broadening effect of microwave signals is analyzed.

PMID- 29047492
TI  - Sharp bend in two-dimensional optical waveguide based on gradient refractive
      index structure.
AB  - In this work, we propose the design of a sharp bend in a two-dimensional optical
      waveguide which has super-ellipse curve boundaries and a gradient refractive
      index structure in its core. Numerical simulations are presented to show the
      efficient light propagation in the waveguide bend, as well as the efficient light
      coupling between the proposed waveguide bend and a straight waveguide, for TE0
      and TM0 modes. The proposed design strategy is also useful for designing other
      compact optical and photonic components.

PMID- 29047493
TI  - Chromatic dispersion measurement along both polarization directions of a
      birefringent hollow-core photonic crystal fiber using spectral interferometry.
AB  - Applications based on photonic crystal fibers depend strongly on their dispersion
      properties that might differ from the desired specifications due to deficiencies
      in the manufacturing process. Since dispersion characteristics might also be
      affected by the placement of the fiber, in this paper the effect of various
      placements on the chromatic dispersion properties of a commercially available HC
      800-02 photonic crystal fiber was investigated between 760 and 870 nm with
      Fourier-transform spectral interferometry. To test the scaling of dispersion with
      fiber length, samples of different lengths ranging from 10 to 97 cm were used in
      the measurements. It was found that the dispersion properties of the orthogonal
      directions were different. The dispersion parameter showed small dependence on
      the placement and fiber length. The polarization-mode dispersion (PMD) of the
      fiber was measured using an indirect and a direct technique. To retrieve the PMD
      directly in the case of the shorter fibers where the fringes were too sparse for
      the Fourier method, the so-called minima-maxima method was employed. The
      precision was comparable with both techniques; however, the direct approach
      proved to be more accurate when longer samples were measured, and the indirect
      method seemed to be more reliable in the case of shorter fibers.

PMID- 29047494
TI  - On the validity of the integral localized approximation for Bessel beams and
      associated radiation pressure forces.
AB  - In this paper we investigate the integral version of the localized approximation
      (ILA)-a powerful technique for evaluating the beam shape coefficients in the
      framework of the generalized Lorenz-Mie theory-as applied to ideal scalar Bessel
      beams (BBs). Originally conceived for arbitrary shaped beams with a propagating
      factor exp(+/-ikz), it has recently been shown that care must be taken when
      applying the ILA for the case of ideal scalar BBs, since they carry a propagating
      factor exp(+/-ikz cos alpha), with alpha being the axicon angle, which cannot be
      smoothly accommodated into its mathematical formalism. Comparisons are
      established between the beam shape coefficients calculated from both ILA and
      exact approaches, assuming paraxial approximation and both on- and off-axis
      beams. Particular simulations of radiation pressure forces are provided based on
      the existing data in the literature. This work helps us in elucidating that ILA
      provides adequate beam shape coefficients and descriptions of ideal scalar BBs up
      to certain limits and, even when it fails to do so, reliable information on the
      physical optical properties of interest can still be inferred, depending on
      specific geometric and electromagnetic aspects of the scatterer.

PMID- 29047495
TI  - Minimum variance control for mitigation of vibrations in adaptive optics systems.
AB  - In this paper, we address the design of a minimum variance controller (MVC) for
      the mitigation of vibrations in modern telescope adaptive optics (AO) systems. It
      is widely accepted that a main source of non-turbulent perturbations is the
      mechanical resonance induced by the wind or the instrumentation systems, such as
      fans and cooling pumps. To adequately mitigate vibrations, the application of
      frequency-based controllers has been considered in the past decade. In this work,
      we express the system model in terms of the tracking of a zero-input signal via
      the MVC. We show that the MVC is an equivalent representation of the linear
      quadratic Gaussian (LQG) controller for the AO system. We also show that by
      developing the MVC, we can obtain different expressions, in terms of transfer
      functions, that offer insights into the behavior and expected performance of the
      controller in the frequency domain. In addition, we analyze the impact of the
      accuracy of the system and perturbations model on the mitigation of vibrations.

PMID- 29047496
TI  - Spatial-spectral holographic real-time correlative optical processor with >100 
      Gb/s throughput.
AB  - The demonstration of an all-optical, ultra-high-speed, time-domain signal
      correlator based on spatial-spectral holographic (SSH) technology is described.
      The fully programmable signal correlator demonstration operates asynchronously
      and continuously on signals with up to 32 GHz of bandwidth and correlative filter
      length exceeding a time-bandwidth product of 104, for the equivalent of teraflop
      scale processing. Experimental demonstrations are presented that show both
      digital and analog correlation capability using phase-shift keyed modulation
      formats to search plain text ASCII data sources for arbitrary phrases at
      continuous line rate throughputs up to 200 Gbps with minimal latency. These high
      bandwidth demonstrations were enabled by improvements in the photonic supporting
      components and cryogenic SSH for RF and microwave signal processing methods.
      Potential application of the SSH real-time correlator for high-bandwidth analog
      or multi-level format signals is discussed.

PMID- 29047497
TI  - Nonlinear refractive index of ultrafast laser inscribed waveguides in gallium
      lanthanum sulphide.
AB  - We demonstrate ultrafast all-optical switching in femtosecond laser inscribed
      nonlinear directional couplers in gallium lanthanum sulphide operated at 1.55
      MUm. We report on the evaluation of the nonlinear refractive index of the
      waveguides forming the directional couplers by making use of the switching
      parameters. The nonlinear refractive index is reduced by the inscription process
      to about 4-5 times compared to bulk material.

PMID- 29047498
TI  - Mode instability dynamics in high-power low-numerical-aperture step-index fiber
      amplifier.
AB  - The study on mode instability (MI) in the large-mode-area fiber is generating
      great interest regarding the high-power applications of fiber lasers. To the best
      of our knowledge, we have investigated for the first time the dynamics of the
      output beam from a kilowatt-level all-fiber amplifier based on the low-numerical
      aperture (<0.04) step-index (SI) fiber before and after the onset of the MI,
      including the temporal dynamics and mode evolution. The temporal power
      fluctuations indicate three evolution stages apart from the onset threshold of
      the MI, defined as stable, transition, and chaotic regions. In addition, the mode
      decomposition technique is utilized to accurately observe and investigate the
      mode evolution and relevant modal content corresponding to the transition and
      chaotic regions in the SI fiber laser for the first time. According to the mode
      decomposition results, the reduction of the extracted power can be explained by
      the high bending loss of the high-order mode excited in the MI process. Finally,
      the difference of MI dynamics between the fiber lasers based on the SI fiber and
      rod-type photonic crystal fiber is discussed.

PMID- 29047499
TI  - Three-dimensional absolute shape measurement by combining binary statistical
      pattern matching with phase-shifting methods.
AB  - This paper presents a novel method that leverages the stereo geometric
      relationship between projector and camera for absolute phase unwrapping on a
      standard one-projector and one-camera structured light system. Specifically, we
      use only one additional binary random image and the epipolar geometric constraint
      to generate a coarse correspondence map between projector and camera images. The
      coarse correspondence map is further refined by using the wrapped phase as a
      constraint. We then use the refined correspondence map to determine a fringe
      order for absolute phase unwrapping. Experimental results demonstrated the
      success of our proposed method.

PMID- 29047500
TI  - Step-by-step guide to reduce spatial coherence of laser light using a rotating
      ground glass diffuser.
AB  - Wide field-of-view imaging of fast processes in a microscope requires high light
      intensities motivating the use of lasers as light sources. However, due to their
      long spatial coherence length, lasers are inappropriate for such applications, as
      they produce coherent noise and parasitic reflections, such as speckle, degrading
      image quality. Therefore, we provide a step-by-step guide for constructing a
      speckle-free and high-contrast laser illumination setup using a rotating ground
      glass diffuser driven by a stepper motor. The setup is easy to build, cheap, and
      allows a significant light throughput of 48%, which is 40% higher in comparison
      to a single lens collector commonly used in reported setups. This is achieved by
      using only one objective to collect the scattered light from the ground glass
      diffuser. We validate our setup in terms of image quality, speckle contrast,
      motor-induced vibrations, and light throughput. To highlight the latter, we
      record Brownian motion of micro-particles using a 100* oil immersion objective
      and a high-speed camera operating at 2000 Hz with a laser output power of only 22
      mW. Moreover, by reducing the objective magnification to 50*, sampling rates up
      to 10,000 Hz are realized. To help readers with basic or advanced optics
      knowledge realize this setup, we provide a full component list, 3D-printing CAD
      files, setup protocol, and the code for running the stepper motor.

PMID- 29047501
TI  - Medium-finesse optical cavity for the stabilization of Rydberg lasers.
AB  - We describe the design, construction, and characterization of a medium-finesse
      Fabry-Perot cavity for simultaneous frequency stabilization of two lasers
      operating at 960 and 780 nm wavelengths, respectively. The lasers are applied in
      experiments with ultracold rubidium Rydberg atoms, for which a combined laser
      linewidth similar to the natural Rydberg linewidth (~10  kHz) is desired. The
      cavity, with a finesse of ~1500, is used to reduce the linewidth of the lasers to
      below this level. By using a spacer made of ultra low expansion (ULE) glass with
      active temperature stabilization, the residual frequency drift is limited to ?1 
      MHz/day. The design optimizes for ease of construction, robustness, and
      affordability.

PMID- 29047502
TI  - Compact microring resonators integrated with grating couplers working at 2  MUm
      wavelength on silicon-on-insulator platform.
AB  - Compact all-pass and add-drop microring resonators (radius=10  MUm) integrated
      with grating couplers working at 2 MUm wavelength are designed, fabricated, and
      characterized on a commercial 340-nm-thick-top-silicon silicon-on-insulator
      platform. They are suitable for high-volume integrated optical circuits at 2 MUm
      wavelength as the fabrication process involved are uncomplicated and
      complementary metal-oxide-semiconductor (CMOS)-process compatible, thus making
      them more convenient to be utilized. The performance of the grating couplers,
      based on four most important parameters, has been simulated and optimized. The
      simulation and experimental results of grating couplers show the lowest coupling
      loss of 4.5 dB and 6.5 Db, respectively. By utilizing the grating couplers to
      couple light in and out from the chip, the designed microring resonators have
      been tested. The experimental results of microring resonators show that an
      extinction ratio of 12 dB and a quality factor of 11,200 can be achieved. To the
      best of our knowledge, this is thus far the smallest microring resonator ever
      demonstrated at this wavelength.

PMID- 29047503
TI  - Subpixel area-based evaluation for crosstalk suppression in quasi-three
      dimensional displays.
AB  - A subpixel area-based evaluation method for an improved slanted lenticular film
      that minimizes the crosstalk in a quasi-three-dimensional (Q3D) display is
      proposed in this paper. To identify an optimal slant angle of the film, a
      subpixel area-based measurement is derived to evaluate the crosstalk among
      viewing regions of the intended subpixel and adjacent unintended subpixel by
      taking the real subpixel shape and black matrix into consideration. The subpixel
      mapping, which corresponds to the optimal slant angle of the film, can then be
      determined. Meanwhile, the viewing zone characteristics are analyzed to balance
      the light intensity in both right and left eye channels. A compact and portable
      Q3D system has been built and appropriate experiments have been applied. The
      results indicate that significant improvements in both crosstalk and resolution
      can be obtained with the proposed technique.

PMID- 29047504
TI  - Broadband, wide-angle and tunable terahertz absorber based on cross-shaped
      graphene arrays.
AB  - Tunable terahertz absorbers composed of periodically cross-shaped graphene arrays
      with the ability to achieve near-unity absorbance are proposed and studied. Our
      results demonstrate that the bandwidth of absorption rate above 90% can reach up
      to 1.13 terahertz by use of a single layer of cross-shaped graphene arrays. By
      simply stacking the double layer cross-shaped graphene with careful design, the
      working bandwidth can be broadened compared with the single-layer graphene-based
      absorber. The proposed absorbers have the properties of being polarization
      insensitive and having large angle tolerance, and the tunability of the Fermi
      level in graphene allows us to realize tunable terahertz absorbers with potential
      interest in integrated terahertz optoelectronic devices.

PMID- 29047505
TI  - Tunable dual-channel filter based on the photonic crystal with air defects.
AB  - We propose a tuning filter containing two channels by inserting a defect layer
      (Air/Si/Air/Si/Air) into a one-dimensional photonic crystal of Si/SiO2, which is
      on the symmetry of the defect. Two transmission peaks (1528.98 and 1564.74 nm)
      appear in the optical communication S-band and C-band, and the transmittance of
      these two channels is up to 100%. In addition, this design realizes multi-channel
      filtering to process large dynamic range or multiple independent signals in the
      near-infrared band by changing the structure. The tuning range will be enlarged,
      and the channels can be moved in this range through the easy control of air
      thickness and incident angle.

PMID- 29047506
TI  - Guided lock of a suspended optical cavity enhanced by a higher-order
      extrapolation.
AB  - Lock acquisition of a suspended optical cavity can be a highly stochastic process
      and is therefore nontrivial. Guided lock is a method to make lock acquisition
      less stochastic by decelerating the motion of the cavity length based on an
      extrapolation of the motion from an instantaneous velocity measurement. We
      propose an improved scheme that is less susceptible to seismic disturbances by
      incorporating the acceleration as a higher-order correction in the extrapolation.
      We implemented the new scheme in a 300-m suspended Fabry-Perot cavity and
      improved the success rate of lock acquisition by a factor of 30.

PMID- 29047507
TI  - Amendment performance of an apodized tilted fiber Bragg grating for a quasi
      distributed-based sensor.
AB  - In this work, the characteristics of reflectivity spectra produced inside a
      reflective-tilted fiber Bragg grating (R-TFBG) are investigated, seeking a
      remarkable performance that could be able to upgrade the sensitivity range for
      temperature-strain sensors of quasi-distribution type. We introduce an optimized
      performance through a comparative investigation among different evaluation
      parameters, such as core radius, tilt angle, and the elite selection of
      apodization profiles, in addition to the traditional parameters, such as grating
      length, L, and index modulation amplitude, Deltan. Regarding the tilt angle, its
      increase affects the full width at half-maximum (FWHM) affirmatively, while
      having a negative impact on the maximum reflectivity. By controlling L and
      Deltan, a compromised solution is achieved to retrieve the maximum reflectivity
      to be around 1.0. Regarding the sidelobes, the Kaiser profile is the best
      candidate that minimized the main sidelobe level (MSL) and raised the sidelobe
      suppression ratio (SLSR) at any tilt angle, while tanh apodization is the best
      choice from the perspective of raising the ramp down sidelobes asymptotic decay.
      The contrasts in the optimization process are examined through investigating the
      R-TFBG quasi-distributed sensors to be applied to a temperature-strain sensing
      system. The objective is to evaluate an assessment for the performance of a
      sensor system that extends the range and efficiency of temperature-strain ranges.
      Based on our analysis, the sensitivity range is upgraded for a temperature change
      to reach 179 degrees C and for strain to be 3000 MUepsilon at a tilt angle of 10
      degrees  with a FWHM of 0.063 nm, attenuation of -154  dB for an MSL of 75.5%,
      and an SLSR of -60  dB/nm.

PMID- 29047508
TI  - Hybrid plasmonic mode converter: theoretical formulation and design with a
      graphical approach.
AB  - The theoretical formulation based on rigorous transmission-line networks is
      developed for a general mode conversion problem and lays the groundwork for a
      simpler yet more efficient graphical design approach for hybrid plasmonic mode
      converters (HPMCs). The concurrence of co- and cross-polarization conversion to
      and among higher-order photonic and HP modes followed by subsequent power
      redistributions and losses over the course of the HPMC can lead to performance
      degradation and largely determines the silicon core thickness. Using gradient
      ascent of the TM polarization fraction incorporated with modal index contours
      sets critical perturbation parameters for required transverse structural
      asymmetry. Polarization reversal estimates are shown to be practically applicable
      for about 60% of the total device length. The mode conversion efficiency (MCE),
      insertion loss (IL), and the polarization conversion efficiency of the proposed
      HPMC (<7*0.4  MUm2) at lambda0=1550  nm are 90.04%, 0.4691 dB, and 99.96%,
      respectively. The 85%-bandwidth of the MCE is 135 nm, while the IL stays below
      0.5 dB over a 68-nm spectral range.

PMID- 29047509
TI  - Beam modulation due to thermal deformation of grating in a spectral beam
      combining system.
AB  - As the power of a spectral beam combining (SBC) system increases, the temperature
      of the multilayer dielectric grating (MDG) inevitably rises under the influence
      of high-power continuous-wave (CW) laser irradiation. Hence, thermal deformation
      of the MDG occurs, along with degeneration of the combined beam properties. In
      this study, we experimentally and theoretically investigate the influence of the
      MDG thermal deformation on the combined beam properties. An experimental setup is
      first proposed, in which beam quality M2, beam profile, and MDG wavefront
      deformation are investigated. The experimental results indicate that the beam
      quality clearly degrades and the MDG wavefront deformation becomes more
      significant with increasing pump-CW power density. On this basis, a calculation
      model for MDG thermal deformation in SBC systems is proposed. The results
      indicate that MDG wavefront deformation becomes more significant, combined beam
      profile becomes deformed, and beam quality of the combined beam degrades with
      increasing power density. Further, thermal expansion of the substrate is a
      crucial factor that induces MDG wavefront deformation and far-field intensity
      modulation.

PMID- 29047510
TI  - Calculation method for laser radar cross sections of rotationally symmetric
      targets.
AB  - The laser radar cross section (LRCS) is a key parameter in the study of target
      scattering characteristics. In this paper, a practical method for calculating
      LRCSs of rotationally symmetric targets is presented. Monostatic LRCSs for four
      kinds of rotationally symmetric targets (cone, rotating ellipsoid, super
      ellipsoid, and blunt cone) are calculated, and the results verify the feasibility
      of the method. Compared with the results for the triangular patch method, the
      correctness of the method is verified, and several advantages of the method are
      highlighted. For instance, the method does not require geometric modeling and
      patch discretization. The method uses a generatrix model and double integral, and
      its calculation is concise and accurate. This work provides a theory analysis for
      the rapid calculation of LRCS for common basic targets.

PMID- 29047511
TI  - Temperature sensing through long period fiber gratings mechanically induced on
      tapered optical fibers.
AB  - In this work the feasibility of employing two well-known techniques already used
      on designing optical fiber sensors is explored. The first technique employed
      involves monomode tapered fibers, which were fabricated using a taper machine
      designed, built, and implemented in our laboratory. This implementation greatly
      reduced the costs and fabrication time allowing us to produce the desired taper
      length and transmission conditions. The second technique used fiber Bragg
      gratings, which we decided to have mechanically induced and for that reason we
      devised and produced our own mechanical gratings with the help of a computer
      numerical control tool. This grating had to be fabricated with aluminum to
      withstand temperatures of up to 600 degrees C. When light traveling through an
      optical fiber reaches a taper it couples into the cladding layer and comes back
      into the core when the taper ends. In the same manner, when the light encounters
      gratings in the fiber, it couples to the cladding modes, and when the gratings
      end, the light couples back into the core. For our experimentation, the tapering
      machine was programmed to fabricate single-mode tapers with 3 cm length, and the
      mechanically induced gratings characteristics were 5 cm length, and had a period
      of 500 MUm and depth of the period of 300 MUm. For the conducting tests, the
      tapered fiber is positioned in between two aluminum slabs, one grooved and the
      other plane. These two blocks accomplish the mechanically induced long period
      grating (LPG); the gratings on the grooved plaque are imprinted on the taper
      forming the period gratings. An optical spectrum analyzer is used to observe the
      changes on the transmission spectrum as the temperature varies from 20 degrees C
      to 600 degrees C. The resultant attenuation peak wavelength in the transmission
      spectrum shifts up to 8 nm, which is a higher shift compared to what has been
      reported using nontapered fibers. As the temperature increases there is no longer
      a shift, but there is significant power loss. Such a characteristic can be used
      as well for sensing applications.

PMID- 29047512
TI  - Nonlinear photonics on-a-chip in III-V semiconductors: quest for promising
      material candidates.
AB  - We propose several designs of nonlinear optical waveguides based on quaternary
      III-V semiconductors AlGaAsSb and InGaAsP. These semiconductor materials have
      been widely used for laser sources. Their nonlinear optical properties, however,
      yet remain unexplored, while the materials definitely hold promise for nonlinear
      photonics on-a-chip. The latter argument is based on the fact that III-V
      compounds tend to exhibit high values of the nonlinear optical susceptibilities,
      while the nonlinear absorption in these materials can be minimized in the
      wavelength range of interest through a proper selection of the material
      composition. We present the modal analysis for the designed waveguide structures
      and show that the effective mode area much less than 1  MUm2 can be achieved
      through a design optimization in each of the two compounds. We also present
      specific waveguide designs that demonstrate zero dispersion at the wavelengths of
      interest. The designed AlGaAsSb and InGaAsP waveguides are thus expected to
      demonstrate high values of the nonlinear coefficient and efficient nonlinear
      optical interactions.

PMID- 29047513
TI  - Bow-shaped caustics from conical prisms: a 13th-century account of rainbow
      formation from Robert Grosseteste's De iride.
AB  - The rainbow has been the subject of discussion across a variety of historical
      periods and cultures, and numerous optical explanations have been suggested.
      Here, we further explore the scientific treatise De iride [On the Rainbow]
      written by Robert Grosseteste in the 13th century. Attempting to account for the
      shape of the rainbow, Grosseteste bases his explanation on the optical properties
      of transparent cones, which he claims can give rise to arc-shaped projections
      through refraction. By stating that atmospheric phenomena are reducible to the
      geometric optics of a conical prism, the De iride lays out a coherent and
      testable hypothesis. Through both physical experiment and physics-based
      simulation, we present a novel characterization of cone-light interactions,
      demonstrating that transparent cones do indeed give rise to bow-shaped caustics-a
      nonintuitive phenomenon that suggests Grosseteste's theory of the rainbow is
      likely to have been grounded in observation.

PMID- 29047514
TI  - Evaluation of adaptively enhanced two-shot fringe pattern phase and amplitude
      demodulation methods.
AB  - Phase-shifting interferometry is a standard tool in optical metrology. Most
      frequently, it needs three or more interferograms to solve the system of fringe
      equations for phase or amplitude retrieval, which limits its time resolution.
      Recently, the topic of two-shot, arbitrary-phase-step fringe pattern phase and
      amplitude demodulation has been flourishing and attracting attention with several
      novel and interesting methods being proposed. In this work, we evaluate six up-to
      date two-shot phase-shifting methods analyzing their main error sources and
      proposing efficient ways to minimize their influence by adaptive filtering using
      the Hilbert-Huang transform.

PMID- 29047515
TI  - Design of a collimated UV-LED exposure unit based on light spread function
      method.
AB  - A collimated and uniform UV-LED exposure unit (EU) applied in a printed circuit
      board is investigated by the light spread function (LSF) method. To accurately
      calculate the source-to-source distance of collimated UV-LED sources and achieve
      uniform irradiance in the exposure area, we propose a regional maximally flat
      condition for the LSF. This regional maximally flat condition contains irradiance
      information from multiple positions in two dimensions. To verify the design
      results, we built this parameter into optical simulation software and used it in
      our LSF method calculations. The obtained collimated UV-LED EU results show
      uniformity and average irradiance values of 98.23% and 43.32  mW/cm2,
      respectively. Thus, we can conclude that the proposed LSF method is effective for
      achieving a uniform irradiance distribution.

PMID- 29047516
TI  - Numerical reproduction and explanation of road surface mirages under grazing
      angle scattering.
AB  - The mirror-like reflection image of the road surface under grazing-angle
      scattering can be easily observed in daily life. It was suggested that road
      surface mirages may occur due to a light-enhancing effect of the rough surface
      under grazing-angle scattering. The main purpose of this work is to explain the
      light-enhancing mechanism of rough surfaces under grazing-angle scattering. The
      off-specular reflection from a random rough magnesium oxide ceramic surface is
      analyzed by using the geometric optics approximation method. Then, the geometric
      optics approximation method is employed to develop a theoretical model to predict
      the observation effect of the grazing-angle scattering phenomenon of the road
      surface. The rough surface is assumed to consist of small-scale rough surface
      facets. The road surface mirage is reproduced from a large number of small-scale
      rough surface facets within the eye's resolution limit at grazing scattering
      angles, as the average bidirectional reflectance distribution function value at
      the bright location is about twice that of the surface in front of the mirage. It
      is suggested that the light-enhancing effect of the rough surface under grazing
      angle scattering is not proper to be termed as "off-specular reflection," since
      it has nothing to do with the "specular" direction with respect to the incident
      direction.

PMID- 29047517
TI  - Relationship between foot eversion and thermographic foot skin temperature after
      running.
AB  - The main instruments to assess foot eversion have some limitations (especially
      for field applications), and therefore it is necessary to explore new methods.
      The objective was to determine the relationship between foot eversion and skin
      temperature asymmetry of the foot sole (difference between medial and lateral
      side), using infrared thermography. Twenty-two runners performed a running test
      lasting 30 min. Skin temperature of the feet soles was measured by infrared
      thermography before and after running. Foot eversion during running was measured
      by kinematic analysis. Immediately after running, weak negative correlations were
      observed between thermal symmetry of the rearfoot and eversion at contact time,
      and between thermal symmetry of the entire plantar surface of the foot and
      maximum eversion during stance phase (r=-0.3 and p=0.04 in both cases). Regarding
      temperature variations, weak correlations were also observed (r=0.4 and p<0.05).
      The weak correlations observed in this study suggest that skin temperature is not
      related to foot eversion. However, these results open interesting future lines of
      research.

PMID- 29047518
TI  - Model of the material removal function and an experimental study on a
      magnetorheological finishing process using a small ball-end permanent-magnet
      polishing head.
AB  - In order to achieve the deterministic finishing of optical components with
      concave surfaces of a curvature radius less than 10 mm, a novel
      magnetorheological finishing (MRF) process using a small ball-end permanent
      magnet polishing head with a diameter of 4 mm is introduced. The characteristics
      of material removal in the proposed MRF process are studied. The model of the
      material removal function for the proposed MRF process is established based on
      the three-dimensional hydrodynamics analysis and Preston's equation. The shear
      stress on the workpiece surface is calculated by means of resolving the presented
      mathematical model using a numerical solution method. The analysis result reveals
      that the material removal in the proposed MRF process shows a positive dependence
      on shear stress. Experimental research is conducted to investigate the effect of
      processing parameters on the material removal rate and improve the surface
      accuracy of a typical rotational symmetrical optical component. The experimental
      results show that the surface accuracy of the finished component of K9 glass
      material has been improved to 0.14 MUm (PV) from the initial 0.8 MUm (PV), and
      the finished surface roughness Ra is 0.0024 MUm. It indicates that the proposed
      MRF process can be used to achieve the deterministic removal of surface material
      and perform the nanofinishing of small curvature radius concave surfaces.

PMID- 29047519
TI  - DBPSK and DQPSK crosstalk in single-span WDM systems using DRA.
AB  - A closed-loop formula is derived for the nonlinear crosstalk degradation due to
      self-phase modulation and cross-phase modulation in a wavelength-division
      multiplexing system. The crosstalk is investigated in differential binary phase
      shift keying (DBPSK) and differential quadrature phase-shift keying (DQPSK)
      schemes. The system under consideration is standard single-mode fiber with a
      single-span distributed Raman amplifier. The backward DBPSK shows a better
      performance with minimum crosstalk performance of 71%, as compared to backward
      DQPSK.

PMID- 29047520
TI  - Comparison of symmetric and asymmetric double quantum well extended-cavity diode
      lasers for broadband passive mode-locking at 780  nm.
AB  - We present a compact, mode-locked diode laser system designed to emit a frequency
      comb in the wavelength range around 780 nm. We compare the mode-locking
      performance of symmetric and asymmetric double quantum well ridge-waveguide diode
      laser chips in an extended-cavity diode laser configuration. By reverse biasing a
      short section of the diode laser chip, passive mode-locking at 3.4 GHz is
      achieved. Employing an asymmetric double quantum well allows for generation of a
      mode-locked optical spectrum spanning more than 15 nm (full width at -20  dB)
      while the symmetric double quantum well device only provides a bandwidth of ~2.7 
      nm (full width at -20  dB). Analysis of the RF noise characteristics of the pulse
      repetition rate shows an RF linewidth of about 7 kHz (full width at half-maximum)
      and of at most 530 Hz (full width at half-maximum) for the asymmetric and
      symmetric double quantum well devices, respectively. Investigation of the
      frequency noise power spectral density at the pulse repetition rate shows a white
      noise floor of approximately 2100  Hz2/Hz and of at most 170  Hz2/Hz for the
      diode laser employing the asymmetric and symmetric double quantum well
      structures, respectively. The pulse width is less than 10 ps for both devices.

PMID- 29047521
TI  - Light and color in the open air-introduction to the feature issue.
AB  - This feature issue reports recent progress in scientific understanding of optical
      phenomena in the natural world, visible to the naked eye. The issue contains
      papers largely arising from presentations given at the 12th International
      Conference on Light and Color in Nature, held at the University of Granada from
      31 May to 3 June 2016.

PMID- 29047522
TI  - On the discrimination of multiple phytoplankton groups from light absorption
      spectra of assemblages with mixed taxonomic composition and variable light
      conditions.
AB  - According to recommendations of the international community of phytoplankton
      functional type algorithm developers, a set of experiments on marine algal
      cultures was conducted to (1) investigate uncertainties and limits in
      phytoplankton group discrimination from hyperspectral light absorption properties
      of assemblages with mixed taxonomic composition, and (2) evaluate the extent to
      which modifications of the absorption spectral features due to variable light
      conditions affect the optical discrimination of phytoplankton. Results showed
      that spectral absorption signatures of multiple species can be extracted from
      mixed assemblages, even at low relative contributions. Errors in retrieved
      pigment abundances are, however, influenced by the co-occurrence of species with
      similar spectral features. Plasticity of absorption spectra due to changes in
      light conditions weakly affects interspecific differences, with errors <21% for
      retrievals of pigment concentrations from mixed assemblages.

PMID- 29047523
TI  - Simulation of small- and wide-angle scattering properties of glass-bead
      retroreflectors.
AB  - Retroreflective materials are extensively used as traffic signs and security
      patterns. These goods are often realized by spherical glass-beads attached to
      some reflective substrate. New applications, especially 3D projection, require
      the precise evaluation and design of the characteristics of light backscattered
      from retroreflective screens. Simulation of such materials is not straightforward
      due to the different optical processes taking place: direct retroreflection
      involving small-angle diffraction effects, and multiple scattering resulting in
      wide-angle diffuse light. We propose a new complex method to describe the
      backscattering properties of glass-bead retroreflectors that uniquely combines
      diffraction calculations with ray tracing based on the microscopic properties of
      the screen. We validated our simulation method by measurements performed on
      commercial retroreflective samples.

PMID- 29047524
TI  - Design of a coaxial light guide producing a wide-angle light distribution.
AB  - A compact light-emitting diode (LED) lighting module with a coaxial light guide
      that can produce a wide-angle light distribution is proposed. The structure of
      the coaxial light guide has a scattering area inside it and a tapered outer
      surface that is able to concentrate all of the rays on the scattering area owing
      to the total internal reflection. The rays diffused and reflected by the
      scattering area are refracted by the tapered outer surface and emitted in a wide
      angle light distribution. A prototype of the LED lighting module was able to
      produce a point-like compact light source that radiates rays with half-intensity
      angle of 274 degrees  and lighting efficiency of 91%.

PMID- 29047525
TI  - Numerical investigation of a microfiber-plane-grating composite optical waveguide
      for gas refractive index sensing.
AB  - In this paper, we propose a microfiber-plane-grating composite optical waveguide
      (MPGCOW), which is formed by immobilizing a tapered microfiber on the surface of
      a plane grating with one defect, for gas refractive index (RI) sensing. Its
      optical properties and gas RI sensing properties are investigated by the finite
      difference time domain method. Results show that the MPGCOW has a photonic stop
      band and is very sensitive to the ambient gas RI variation. The largest gas RI
      sensing sensitivity of 486.67 nm/RIU and detection limit of 2*10-6 are obtained
      by immersing the structure in the mixture gas of N2 and He with various mixture
      ratios.

PMID- 29047526
TI  - Drifts in real-time partial wavefront correction and how to avoid them.
AB  - In visual experiments that require real-time partial correction of wavefront
      aberrations, small errors occur that accumulate over time and lead to drifts in
      Zernike coefficients of the uncorrected aberrations. A simple algorithm that does
      not require the inclusion of an additional optical path to obtain independent
      measurements of the eye's aberrations is described here, and its effectiveness in
      preventing these drifts is demonstrated.

PMID- 29047527
TI  - Invertible propagator for plane wave illumination of forward-scattering
      structures.
AB  - Propagation of directed waves in forward-scattering media is considered. It is
      assumed that the evolution of the wave field is governed by the standard
      parabolic wave equation. An efficient one-step momentum-space propagator,
      suitable for a tilted plane wave illumination of extended objects, is derived. It
      is expressed in terms of a propagation operator that transforms (the complex
      exponential of) a linogram of the illuminated object into a set of its
      diffraction patterns. The invertibility of the propagator is demonstrated, which
      permits a multiple-shot scatter correction to be performed, and makes the
      solution especially attractive for either projective or tomographic imaging. As
      an example, high-resolution tomograms are obtained in numerical simulations
      implemented for a synthetic phantom, with both refractive and absorptive
      inclusions.

PMID- 29047528
TI  - Plasmonic wavelength demultiplexer with a ring resonator using high-order
      resonant modes.
AB  - In this paper, we propose a novel wavelength demultiplexer based on metal
      insulator-metal plasmonic waveguides with a nanoscale ring resonator. Its
      transmission characteristics are numerically studied using finite element method
      (FEM) simulations, and the eigenwavelengths of the ring resonator are
      theoretically calculated. For the proposed structure, we found that the ratio of
      the orders of resonant transmittance peaks for two different high-order modes of
      the ring resonator is close to the ratio of the two communication wavelengths
      1310 and 1550 nm. These resonance wavelengths of the demultiplexer are
      effortlessly tuned by varying the refractive index of the material in the ring
      resonator and the geometrical parameters of the structure. The results simulated
      by FEM agree well with those from the resonant theory of the ring resonator. The
      presented structures will have significant potential applications in highly
      integrated plasmonic devices.

PMID- 29047529
TI  - Color design model of high color rendering index white-light LED module.
AB  - The traditional white-light light-emitting diode (LED) is packaged with a single
      chip and a single phosphor but has a poor color rendering index (CRI). The next
      generation package comprises two chips and a single phosphor, has a high CRI, and
      retains high luminous efficacy. This study employs two chips and two phosphors to
      improve the diode's color tunability with various proportions of two phosphors
      and various densities of phosphor in the silicone used. A color design model is
      established for color fine-tuning of the white-light LED module. The maximum
      difference between the measured and color-design-model simulated CIE 1931 color
      coordinates is approximately 0.0063 around a correlated color temperature (CCT)
      of 2500 K. This study provides a rapid method to obtain the color fine-tuning of
      a white-light LED module with a high CRI and luminous efficacy.

PMID- 29047530
TI  - Calibration method for a large-scale structured light measurement system.
AB  - The structured light method is an effective non-contact measurement approach. The
      calibration greatly affects the measurement precision of structured light
      systems. To construct a large-scale structured light system with high accuracy, a
      large-scale and precise calibration gauge is always required, which leads to an
      increased cost. To this end, in this paper, a calibration method with a planar
      mirror is proposed to reduce the calibration gauge size and cost. An out-of-focus
      camera calibration method is also proposed to overcome the defocusing problem
      caused by the shortened distance during the calibration procedure. The
      experimental results verify the accuracy of the proposed calibration method.

PMID- 29047531
TI  - Image restoration in fiber-coupled imagers using space-variant impulse response
      characterization.
AB  - Fiber-coupled image sensors have attracted interest in recent years for high
      resolution conformal image transfer, including mapping of the spherical image
      surface of a monocentric wide-angle lens to one or more flat focal plane sensors.
      However, image resolution is lost due to fiber bundle defects, moire from lateral
      fiber-sensor misalignment, and blur due to the nonzero gap between fiber bundle
      and the image sensor. Here we investigate whether subpixel impulse response
      characterization of the strongly shift-variant impulse response can be used with
      existing image-processing techniques to recover the resolution otherwise lost in
      image transfer. We show that the submicrometer impulse response is experimentally
      repeatable, and can be used to recover image data and reveal fine features of the
      input surface structure of a 2.5 MUm pitch fiber bundle.

PMID- 29047532
TI  - Experimental measurements of the magnitude and phase response of high-frequency
      modulated light underwater.
AB  - The propagation behavior of high-frequency intensity-modulated signals through
      turbid water is of significant interest for underwater laser ranging, imaging,
      and communications. Prior experimental measurements have focused only on the
      magnitude response of the underwater optical channel to forward-scattered and
      unscattered modulated light. In this study we include, for the first time to our
      knowledge, both the magnitude and phase of the underwater optical channel to
      forward-scattered light. The magnitude and phase response is measured out to 1
      GHz, using three different artificial scattering agents in scattering
      environments in excess of 25 attenuation lengths. The phase response provides
      additional insight into the behavior of forward-scattered light carrying high
      frequency intensity modulation.

PMID- 29047533
TI  - Development of a multi-band photoacoustic tomography imaging system based on a
      capacitive micromachined ultrasonic transducer array.
AB  - Photoacoustic tomography (PAT) as a hybrid technology combines the high optical
      contrast and high acoustic resolution in a single imaging modality. However, most
      of the available PAT systems cannot comprehensively or accurately characterize
      biological systems at multiple length scales due to the use of narrow bandwidth
      commercial ultrasonic transducers. In this study, we fabricated a novel multi
      band capacitive micromachined ultrasonic transducer (CMUT) array, and first
      developed a CMUT-based multi-band photoacoustic tomography (MBPAT) imaging
      system. The MBPAT imaging system was examined by the phantom experiment, and then
      was successfully applied to image the zebrafish in vivo. The imaging results
      indicated that CMUT-array-based MBPAT can provide a more comprehensive and
      accurate characterization of biological tissues, which exhibit the potential of
      MBPAT/CMUT in various areas of biomedical imaging.

PMID- 29047534
TI  - Efficient self-frequency-doubling Nd:GdCOB green laser at 545  nm pumped by a 796
      nm laser diode.
AB  - A 796 nm laser-diode (LD)-pumped self-frequency-doubling Nd:GdCa4O(BO3)3
      (Nd:GdCOB) green laser is first demonstrated. With 2.93 W of 796 nm LD pump
      power, a maximum power of 460 mW green laser at 545 nm has been achieved. The
      optical conversion efficiency of 15.8% is higher than that pumped with a 808 nm
      LD. As the pump wavelength shifts toward 796 nm, the output power and optical
      conversion efficiency increase.

PMID- 29047535
TI  - Illumination-direction multiplexing Fourier ptychographic microscopy using
      hemispherical digital condensers.
AB  - Simulations were conducted to explore a broader collection of possible
      illumination patterns realizable using a white-light-emitting hemispherical
      digital condenser. Several simple, but practical, illumination patterns were
      selected and used in experiments where a sample was illuminated simultaneously
      from different directions. The illumination-direction multiplexing (IDM) Fourier
      ptychographic microscopy (FPM) method was successfully used for imaging and phase
      recovery. This study suggests that IDM-FPM can be used for imaging photonic
      crystals with subwavelength periods using traditional microscope condensers with
      variable numerical aperture.

PMID- 29047536
TI  - Phase-sensitive optical time-domain reflectometric system based on a single
      source dual heterodyne detection scheme.
AB  - A phase-sensitive optical time-domain reflectometric (phi-OTDR) system based on a
      novel single-source dual heterodyne detection scheme is proposed and
      demonstrated. It uses the optical beat-frequency signals as the local oscillator
      signal containing the modulated frequency, frequency drift and phase fluctuation,
      while the signal to be detected contains all the forgoing spectral components, in
      addition to the vibration signal under measurement. Frequency mixing serves to
      isolate the pure vibration signal from the omnipresent residual frequency and
      phase fluctuations caused by a less strictly synchronous clock, inherent
      characteristics of the laser and the acousto-optical modulator, and environment
      temperature changes. With a reduced burden on data processing, better real-time
      performance is achieved as well. Using probe light pulses of 4 kHz repetition
      rate and 80 ns pulse width, a 9 m spatial resolution has been achieved on a 24.6
      km sensing fiber, with a detectable frequency range from 5 Hz to 1.715 kHz, with
      a signal-to-noise ratio greater than 23.5 dB. All the above parameters are close
      to the maximum theoretical values. The drastically improved system demodulation
      characteristics foreshadow better performance and improved reliability in
      engineering applications.

PMID- 29047537
TI  - Study of the influence of the agarose hydrogel layer thickness on sensitivity of
      the coated silica microsphere resonator to humidity.
AB  - In this paper, we investigate both theoretically and experimentally the influence
      of the agarose hydrogel layer thickness on the sensitivity of a proposed relative
      humidity (RH) sensor based on a silica microsphere resonator coated with agarose
      hydrogel. The operating principle of the sensor relies on excitation of
      whispering gallery modes (WGMs) in the coated silica microsphere using the
      evanescent field of a tapered fiber. A change in the ambient relative humidity is
      detected by measuring the wavelength shift of the WGMs in the transmission
      spectrum of the tapered fiber. Using perturbation theory, we analyze the
      influence of the agarose coating thickness on the sensitivity of the proposed
      sensor and compare the results of this analysis with experimental findings for
      different coating layer thicknesses. We demonstrate that an increase in the
      coating layer thickness initially leads to an increase in the sensitivity to RH
      and reaches saturation at higher values of the agarose layer thickness. The
      results of the study are useful for the design and optimization of microsphere
      sensor parameters to meet a performance specification.

PMID- 29047538
TI  - Detection of heavy metal Cd in polluted fresh leafy vegetables by laser-induced
      breakdown spectroscopy.
AB  - In seeking a novel method with the ability of green analysis in monitoring toxic
      heavy metals residue in fresh leafy vegetables, laser-induced breakdown
      spectroscopy (LIBS) was applied to prove its capability in performing this work.
      The spectra of fresh vegetable samples polluted in the lab were collected by
      optimized LIBS experimental setup, and the reference concentrations of cadmium
      (Cd) from samples were obtained by conventional atomic absorption spectroscopy
      after wet digestion. The direct calibration employing intensity of single Cd line
      and Cd concentration exposed the weakness of this calibration method.
      Furthermore, the accuracy of linear calibration can be improved a little by
      triple Cd lines as characteristic variables, especially after the spectra were
      pretreated. However, it is not enough in predicting Cd in samples. Therefore,
      partial least-squares regression (PLSR) was utilized to enhance the robustness of
      quantitative analysis. The results of the PLSR model showed that the prediction
      accuracy of the Cd target can meet the requirement of determination in food
      safety. This investigation presented that LIBS is a promising and emerging method
      in analyzing toxic compositions in agricultural products, especially combined
      with suitable chemometrics.

PMID- 29047539
TI  - Demodulation of multimodulation artifacts in Fourier-transform infrared
      spectroscopy.
AB  - Fourier-transform infrared (FTIR) spectra can show artifacts, for example, in the
      vicinity of the overtone when light is doubly modulated. Technical approaches,
      i.e., modifications to the spectrometer setup, have been devised in order to
      reduce those artifacts. Elimination of the artifacts was achieved only partly but
      at the expense of a loss of intensity or an increase in the noise level. We
      devised a computational demodulation scheme that is capable of almost fully
      reducing the artifacts with neither a loss of spectroscopic information nor an
      increase in the noise level. This has been demonstrated for the FTIR absorption
      spectra in the overtone regions of HCl(g) and CH4(g).

PMID- 29047540
TI  - Single-pixel compressive diffractive imaging with structured illumination.
AB  - We present a method for diffractive imaging with a single photodetector and
      structured illumination based on compressive sensing. A complex-amplitude object
      is sequentially illuminated with randomly structured coherent light patterns, and
      the intensities of each propagating field are measured with a single
      photodetector. This measurement process does not use any reference light or
      imaging optics. The object complex field is reconstructed from the sequentially
      measured intensities with an algorithm in which compressive sensing and phase
      retrieval are integrated. We demonstrate the proposed method experimentally.

PMID- 29047541
TI  - Effect of Cu/Ga ratio on deep-level defects in CuGaSe2 thin films studied by
      photocapacitance measurements with two-wavelength excitation.
AB  - The effect of the Cu/Ga ratio on properties of deep-level defects in CuGaSe2 thin
      films were studied, using photocapacitance methods with two-wavelength
      excitation. The transient photocapacitance method, using a monochromatic probe
      light, determined two kinds of defects located at 0.8 eV and 1.5 eV above the
      valence band, respectively, the positions of which kept almost constant
      regardless of Cu/Ga ratio. In addition to the probe light, laser light with a
      wavelength of 1550 nm corresponding to 0.8 eV was then used to study the
      saturation effect of the deep-level defect at 0.8 eV above the valence band. The
      results suggest that the defect level at 0.8 eV acts as a recombination center at
      room temperature, and it becomes more effective in CuGaSe2 films with a lower
      Cu/Ga ratio.

PMID- 29047542
TI  - Astigmatic transforms of an optical vortex for measurement of its topological
      charge.
AB  - We obtain analytical expressions for the complex amplitudes of optical vortices
      deformed by astigmatic transforms, i.e., passed either through a cylindrical lens
      or through an inclined spherical lens. We also obtain similar analytical
      expressions describing propagation of an optical vortex generated when a Gaussian
      beam illuminates an inclined spiral phase plate (SPP) or when an elliptic
      Gaussian beam illuminates a SPP (not inclined). All these optical vortices with a
      topological charge (TC) n are described by the n-th order Hermite polynomial with
      a complex argument. It is shown that the argument is real only on a straight line
      in the transverse plane of the laser beam. There are n intensity nulls on this
      line. The treated here astigmatic transforms are used to determine the integer TC
      of optical vortices. We conduct a comparative experimental study of different
      astigmatic transforms and we show that the transform with a cylindrical lens is
      the best for determining the TC. Unlike other similar works, in this study we
      achieve transformation of n-degenerate intensity null of an optical vortex with
      the TC n=100 into n isolated first-order intensity nulls.

PMID- 29047543
TI  - Equivalence of internal and external mixture schemes of single scattering
      properties in vector radiative transfer.
AB  - Polarized radiation fields in a turbid medium are influenced by single-scattering
      properties of scatterers. It is common that media contain two or more types of
      scatterers, which makes it essential to properly mix single-scattering properties
      of different types of scatterers in the vector radiative transfer theory. The
      vector radiative transfer solvers can be divided into two basic categories: the
      stochastic and deterministic methods. The stochastic method is basically the
      Monte Carlo method, which can handle scatterers with different scattering
      properties explicitly. This mixture scheme is called the external mixture scheme
      in this paper. The deterministic methods, however, can only deal with a single
      set of scattering properties in the smallest discretized spatial volume. The
      single-scattering properties of different types of scatterers have to be averaged
      before they are input to deterministic solvers. This second scheme is called the
      internal mixture scheme. The equivalence of these two different mixture schemes
      of scattering properties has not been demonstrated so far. In this paper,
      polarized radiation fields for several scattering media are solved using the
      Monte Carlo and successive order of scattering (SOS) methods and scattering media
      contain two types of scatterers: Rayleigh scatterers (molecules) and Mie
      scatterers (aerosols). The Monte Carlo and SOS methods employ external and
      internal mixture schemes of scatterers, respectively. It is found that the
      percentage differences between radiances solved by these two methods with
      different mixture schemes are of the order of 0.1%. The differences of Q/I, U/I,
      and V/I are of the order of 10-5~10-4, where I, Q, U, and V are the Stokes
      parameters. Therefore, the equivalence between these two mixture schemes is
      confirmed to the accuracy level of the radiative transfer numerical benchmarks.
      This result provides important guidelines for many radiative transfer
      applications that involve the mixture of different scattering and absorptive
      particles.

PMID- 29047544
TI  - Potential material for fabricating optical mirrors: polished diamond coated
      silicon carbide.
AB  - Polished diamond coated silicon carbide can be a potential candidate material for
      making optical mirrors, due to the excellent properties. At present, five typical
      types of diamond films are deposited on RB-SiC substrates by hot filament
      chemical vapor deposition, and then polished by mechanical polishing. It is found
      that the boron-doped micro-crystalline and undoped nano-crystalline composite
      diamond (BDMC-UNCCD) coated specimen performs the best before, during, and after
      polishing. The film surface composed of nano-sized diamond grains has relatively
      low surface roughness and hardness, which are beneficial for the efficient
      polishing, and under the present condition only such a surface can be completely
      polished to a homogeneous mirror surface. The micro-sized diamond grains and the
      boron incorporation in the underlying BDMCD layer can enhance the film-substrate
      adhesion, which plays an important role in the film integrity during the
      polishing or subsequent applications. In conclusion, the polished BDMC-UNCCD
      coated RB-SiC specimen indeed shows low surface roughness (Ra=5.41  nm), high
      hardness (71.47 GPa), high elastic modulus (746 GPa), favorable surface shape
      accuracy (RMS=0.083lambda), and considerable reflectivity in the short-wavelength
      range.

PMID- 29047545
TI  - Differentiation of soot particulates in air using polarized light scattering
      method.
AB  - Soot is the main light-absorbing particle in the visible range. Light scattering
      and absorption by air particulates can change their optical polarization state,
      and the information upon polarization can reflect the nature of particles. In
      this paper, a polarization scattering method has been developed for the
      feasibility study concerning differentiating soot from other typical air
      particulates. Simulation results indicate that S2/S0 at the scattering angle of
      115 degrees  can identify the soot particles specifically. Single component
      experiments and double composition experiments are carried out, which confirm the
      validity of differentiating soot by a polarization indicator. These preliminary
      simulations, experiments, and field tests also imply the potential of
      polarization characterization applied in air pollutants analysis.

PMID- 29047546
TI  - Beam drift error and control technology for scanning beam interference
      lithography.
AB  - To improve the quality of grating masks made by scanning beam interference
      lithography, this article established a mathematical model of step-scanning
      exposure and analyzed the effects of the beam drift error on the interference
      image. Beam angle drift can be decomposed into the drift error deltax in the
      exposure plane (XOZ plane) and the drift error deltay perpendicular to the plane.
      Analysis shows that the deltax has a major impact on the interference fringes
      during exposure, which may affect the precision of phase lock. deltay leads to
      the appearance of deflected interference strips and affects the exposure dose.
      When a low-frequency drift error appears in the light path, the exposure contrast
      on the photoresist will decrease with the exposure process, which makes the
      fabrication of large-size diffraction gratings difficult. Furthermore, taking
      advantage of the characteristics of a scanning beam interference lithography
      system, an exposed beam stable system was designed that can effectively suppress
      the low-frequency drift of the beam. The total beam angle control accuracy is
      better than the 2.7 MUrad, and position control accuracy is better than 3.9 MUm
      (both for 1sigma), which achieves the expected goal of the design.

PMID- 29047547
TI  - Electrically tunable all-optical diode in a one-dimensional photonic crystal
      structure.
AB  - All-optical-diode tunability with externally applied voltage in a one-dimensional
      photonic crystal structure of arrangement (BA)5/AgLiNbO3Ag/(AB)5(AABB)5 was
      investigated. It is an asymmetric hybrid Fabry-Perot resonator which is composed
      of distributed Bragg reflector segments (AB5) containing the linear (B layers)
      and nonlinear (A layers) optical materials. The LiNbO3, (LNO) sandwiched with two
      pairs Ag layers, is employed as a defect. The electro-optical (EO) effect and
      optical nonlinear response (Kerr effect) of LNO is considered. The linear
      transmittance (LT) spectrum, nonlinear transmission (NT) curves and field
      distribution, for left to right (L-R) and right to left (R-L) incidents at
      different applied voltages are graphically illustrated. Results show that with an
      increase in the applied voltage, L-R and R-L NT curves deflect, amplify, and
      compress in comparison to zero applied voltage. At negative voltages, due to
      accumulation of the EO and Kerr effects, variations are more sensitive. The EO
      effect in LNO causes tunability of the LT spectrum, and the Kerr effect in
      nonlinear layers dynamically tunes the optical bistability threshold. The results
      of this study can be useful in designing externally tunable basic elements for
      optoelectronic devices.

PMID- 29047548
TI  - Characterization and control of the electro-optic phase dispersion in lithium
      niobate modulators for wide spectral band interferometry applications in the mid
      infrared.
AB  - Mid-infrared wideband modulation (3.2-3.7 MUm) is achieved in an electro-optic Y
      junction using lithium niobate waveguides in TE polarized light. Comparison
      between external (scanning mirror) and internal (electro-optical) modulation
      allows studying the chromatic polynomial dependence of the relative phase.
      Internal modulation consists on a VAC ramp up to 370 V at 0.25 Hz, applied over
      14 mm long electrodes with 14 MUm separation. The overall VpiLpi obtained is 17.5
      V.cm, meaning that using a 300 V generator we can actively scan and track the
      whole L-band (3.4-4.1 MUm) wideband fringes. We observe a dramatic reduction of
      the coherence length under electro-optic modulation, which is attributed to a
      strong nonlinear dependence of the electro-optic effect on the wavelength upon
      application of such high voltages. We study the effect of applying a VDC offset,
      from -50  V to 200 V (50 V step). We characterize this dispersion and propose an
      improved dispersion model that is used to show active dispersion compensation in
      wideband fringe modulation in the mid-infrared. This can be useful for long
      baseline interferometry or pulse compression applications when light propagates
      along fibers, in order to compensate for chromatic effects that induce
      differential dispersion or pulse spreading, respectively.

PMID- 29047549
TI  - Compact, semi-passive beam steering prism array for solar concentrators.
AB  - In order to maximize solar energy utilization in a limited space (e.g.,
      rooftops), solar collectors should track the sun. As an alternative to rotational
      tracking systems, this paper presents a compact, semi-passive beam steering prism
      array which has been designed, analyzed, and tested for solar applications. The
      proposed prism array enables a linear concentrator system to remain stationary so
      that it can integrate with a variety of different solar concentrators, and which
      should be particularly useful for systems which require a low profile (namely
      rooftop-mounted systems). A case study of this prism array working within a
      specific rooftop solar collector demonstrates that it can boost the average daily
      optical efficiency of the collector by 32.7% and expand its effective working
      time from 6 h to 7.33 h. Overall, the proposed design provides an alternative way
      to "follow" the sun for a wide range of solar thermal and photovoltaic
      concentrator systems.

PMID- 29047550
TI  - Background oriented schlieren measurement of the refractive index field of air
      induced by a hot, cylindrical measurement object.
AB  - To optically capture the topography of a hot measurement object with high
      precision, the light deflection by the inhomogeneous refractive index field
      induced by the heat transfer from the measurement object to the ambient medium
      has to be considered. We used the 2D background oriented schlieren method with
      illuminated wavelet background, an optical flow algorithm, and Ciddor's equation
      to quantify the refractive index field located directly above a red-glowing, hot
      measurement object. A heat transfer simulation has been implemented to verify the
      magnitude and the shape of the measured refractive index field. Provided that no
      forced external flow is disturbing the shape of the convective flow originating
      from the hot object, a laminar flow can be observed directly above the object,
      resulting in a sharply bounded, inhomogeneous refractive index field.

PMID- 29047551
TI  - Estimation of order parameter of a liquid crystal variable retarder using
      Haller's approximation.
AB  - We use a liquid crystal variable retarder (LCVR) for polarization modulation of
      the input beam in a polarimeter intended for solar observations. It is known that
      the retardance of LCVR depends on the voltage and temperature. Voltage at a
      constant temperature is used for fast modulation. However, fluctuations in the
      temperature reduce the accuracy in the polarimetric measurements. In order to
      understand these, we have performed calibration of the LCVR with respect to
      temperature and estimated the different parameters, critical exponent (beta),
      maximum retardance (delta0), and order parameter (S) of the liquid crystal using
      Haller's approximation. We also study the dependence of these parameters with
      voltage. It is observed that the change in order parameter with change in
      temperature varies linearly with voltage in the range of 1-7 V.

PMID- 29047552
TI  - Cascaded chirped narrow bandpass filter with flat-top based on two-dimensional
      photonic crystals.
AB  - We propose a structure of a cascaded chirped narrow bandpass filter with a flat
      top based on two-dimensional (2D) photonic crystals (PhCs). The filter discussed
      here consists of three filter units, each with a resonator and two reflectors.
      Coupled mode theory and transfer matrix method are methodologies applied in the
      analysis of the features. The calculations show that the bandwidth of the filter
      can be adjusted by changing the distances between resonators and reflectors, and
      based on this, a flat-top response can be achieved by chirped-cascading the
      filter units. According to the theoretical model, we design a narrow bandpass
      filter based on 2D PhCs with a triangular lattice of air holes, the parameters of
      which are calculated using the finite element method. The simulation results show
      that the filter has a center frequency of 193.40 THz, an insertion loss of 0.18
      dB, a flat bandwidth of 40 GHz, and ripples of about 0.2 dB in the passband. The
      filter is suitable for dense-wavelength-division-multiplexed optical
      communication systems with 100 GHz channel spacing.

PMID- 29047553
TI  - Laser characteristics of Nd3+-doped calcium barium niobate ferroelectric crystal
      at 1.06 and 1.34  MUm.
AB  - We report on diode-pumped Nd3+-doped calcium barium niobate ferroelectric crystal
      (Nd:CBN-28) lasers at 1.06 and 1.34 MUm. The maximum output power of the 1.06 MUm
      laser reaches 0.69 W in the continuous-wave regime, which is believed to be the
      highest output power with Nd:CBN-28 crystal to date. Using a chopper to modulate
      the pump, the highest output power further improves to 0.77 W. Passively Q
      switched laser operation at 1.06 MUm, using a Cr:YAG saturable absorber, is
      realized with a maximum average output power of 89 mW, a pulse width of 220 ns,
      and a pulse energy 10.8 MUJ. A quasi-continuous-wave laser at 1.34 MUm with a
      chopper is also demonstrated with maximum output power of 56 mW. The scaled
      output power in the fundamental wave should be favorable for the investigation on
      broadband nonlinear self-frequency conversion into visible.

PMID- 29047554
TI  - Scattering of cylindrical waves by a chiral-coated cylindrical reflector placed
      in chiral background.
AB  - The scattering of cylindrical waves by a chiral-coated cylindrical reflector
      placed in chiral background has been investigated using numerical simulations.
      The expressions for electric and magnetic fields inside the chiral coating and in
      the chiral background have been derived using the wavefield decomposition
      approach. It is postulated that the scattering gain can be controlled by varying
      the cylindrical wave source location, thickness of coating, chirality of coating,
      and chirality of background medium. It is shown that by increasing the chirality
      of coating for a chiral-coated cylindrical reflector placed in free space, the
      scattering gain in the forward direction increases, whereas the scattering gain
      in the backward direction decreases. It is further asserted that a strong chiral
      coated cylindrical reflector placed in a certain chiral background guides most of
      the scattered field toward the rear side of the reflector. It is also observed
      that the scattering gain pattern becomes isotropic provided the chiral, strong
      chiral, and chiral nihility coated cylindrical reflectors are placed in a chiral
      nihility background. A cloaking phenomenon associated with a chiral-coated
      reflector placed in a chiral background at a specific observation angle is also
      discussed.

PMID- 29047555
TI  - Influence of residual carbon impurities in a heavily Mg-doped GaN contact layer
      on an Ohmic contact.
AB  - The influence of residual carbon impurities incorporated into a heavily Mg-doped
      GaN layer has been studied systematically according to the relation between the
      carbon concentration and specific contact resistance. Furthermore, the results of
      temperature-dependent current-voltage characteristics and the photoluminescence
      spectra indicate that a proper concentration of residual carbon impurities can
      improve the performance of Ohmic contact by introducing deep-level defects to
      enhance the variable-range-hopping conduction.

PMID- 29047556
TI  - Wide-angle, polarization-insensitive, and broadband metamaterial absorber based
      on multilayered metal-dielectric structures.
AB  - A wide-angle, polarization-insensitive, and broadband metamaterial absorber (MA)
      based on multilayered metal-dielectric structures was designed and investigated
      using the finite-difference time-domain solution. The device exhibited
      polarization-insensitive absorption in the 475-592 nm range, with the absorption
      higher than 95%. At the same time, the broadband absorption was nearly unaffected
      for incident angles below 50 degrees . To understand this absorption mechanism of
      this broadband MA, we investigated the magnetic field distributions at the
      resonance wavelength. Different metallic layers yielded different resonant
      wavelengths, leading to the observed high absorption in the broadband spectrum.
      For broadband MAs, the absorption spectrum can be expanded by adjusting
      structural parameters.

PMID- 29047557
TI  - Generating superimposed Bessel beams with a volume holographic axicon.
AB  - Quasi-Bessel beams (QBB) with different profiles are generated with an axicon
      telescope system. Beam profiles are found to vary with different axicon-telescope
      distance delta. QBBs are stored as volume holograms in a photorefractive crystal.
      Reconstructions of the QBBs are focused by the recording axicon to produce
      superimposed Bessel beams (SBBs) with oscillating cores. SBBs formed through this
      method have different oscillation periods that range from 4.3 to 6.1 cm. We
      demonstrate that periodicity is dependent on delta. Our method allows tunability
      of the SBB period through a simple rearrangement of optical elements.

PMID- 29047558
TI  - >1  kW all-fiberized narrow-linewidth polarization-maintained fiber amplifiers
      with wavelength spanning from 1065 to 1090  nm.
AB  - We demonstrate all-fiberized, kilowatt-level, narrow-linewidth, Yb-doped and
      polarization-maintained (PM) amplifiers with a central wavelength spanning from
      1065 to 1090 nm. The laser system consists of a tunable single-frequency laser
      seed and multistage PM fiber amplifiers in the master oscillator power amplifier
      configuration. The stimulated Brillouin scattering effect is suppressed by phase
      modulation based on a white noise source. The linewidth (Deltalambda~0.12  nm at
      1 kW), polarization extinction ratio (PER>13  dB) and beam quality (M2~1.2) are
      well maintained during the power scaling process, and the slope efficiency of
      this system is 70.8%.

PMID- 29047559
TI  - Full-color reflector using vertically stacked liquid crystal guided-mode
      resonators.
AB  - In this work, we proposed a full-color reflector using three stacked red (R),
      green (G), and blue (B) reflection gratings which are combined with the tunable
      90 degrees  twisted nematic liquid crystals (TNLCs). The color reflector based on
      guided-mode resonance (GMR) gratings reflects strongly at the resonance
      wavelength. The optical reflectivity of GMR gratings can then be controlled by
      using 90 degrees  TNLCs to change the polarization of incident light. The optical
      characteristics and the chromaticity of the designed reflectors were evaluated by
      simulation. An individual RGB chip with/without LC was demonstrated
      experimentally. The fabricated GMR reflector for red exhibits a high TE/TM
      polarization ratio of >10:1 and 80% optical reflectivity at resonant wavelength,
      while the GMR reflector for blue only allows 60% optical reflectivity and a
      degraded polarization ratio of 3:1 mainly due to high optical absorption of
      silicon. Nevertheless, the silicon-based GMR reflector enables a wide reflection
      bandwidth, so a full-color reflector can be realized by vertically stacking RGB
      tunable reflectors. The proposed full-color reflector therefore exhibits a wide
      gamut color space with low driving voltage of <3  V, showing its promise for use
      in energy-saving reflective information systems.

PMID- 29047560
TI  - Optical function of the finite-thickness corrugated pellicle of euglenoids.
AB  - We explore the electromagnetic response of the pellicle of selected species of
      euglenoids. These microorganisms are bounded by a typical surface pellicle formed
      by S-shaped overlapping bands that resemble a corrugated film. We investigate the
      role played by this structure in the protection of the cell against UV radiation.
      By considering the pellicle as a periodically corrugated film of finite
      thickness, we applied the C-method to compute the reflectance spectra. The far
      field results revealed reflectance peaks with a Q-factor larger than 103 in the
      UV region for all the illumination conditions investigated. The resonant behavior
      responsible for this enhancement has also been illustrated by near-field
      computations performed by a photonic simulation method. These results confirm
      that the corrugated pellicle of euglenoids shields the cell from harmful UV
      radiation and open up new possibilities for the design of highly UV-reflective
      surfaces.

PMID- 29047561
TI  - Impact of a counter-rotating planetary rotation system on thin-film thickness and
      uniformity.
AB  - Planetary rotation systems incorporating forward- and counter-rotating planets
      are used as a means of increasing coating-system capacity for large oblong
      substrates. Comparisons of planetary motion for the two types of rotating systems
      are presented based on point tracking for multiple revolutions as well as
      comparisons of quantitative thickness and uniformity. Counter-rotation system
      geometry is shown to result in differences in thin-film thickness relative to
      standard planetary rotation for precision optical coatings. This systematic error
      in thin-film thickness will reduce deposition yields for sensitive coating
      designs.

PMID- 29047562
TI  - High-order mode conversion based on adiabatical mode evolution for mode division
      multiplexing applications.
AB  - Mode conversion based on adiabatical mode evolution in a two-core configuration
      is investigated. The configuration can convert all the launching modes to higher
      order modes from one port and convert all the launching modes to lower-order
      modes from another port. Mode conversion between the two degenerated high-order
      modes is also demonstrated numerically. The mode conversion feature is only
      dependent on the relationship between the effective mode indices of the two cores
      in the configuration, which shows the characteristics of high flexibility and
      large fabrication tolerance.

PMID- 29047563
TI  - Analytical model of amplified spontaneous emission with different thickness anti
      ASE caps for thin disk lasers.
AB  - The amplified spontaneous emission (ASE) effect is a major factor affecting
      large, high gain Yb:YAG thin disk lasers. In this paper, the analytical model is
      built to estimate the ASE photon flux density of thin disk crystals with
      different thickness anti-ASE caps. Theoretical analysis shows that it is
      unnecessary to use a critical thickness anti-ASE cap to suppress the ASE effect.
      At the same time, adjusting the coupler reflectivity of the resonator is an
      effective way to decrease the ASE effect and decrease the thickness of the anti
      ASE cap to effectively suppress the ASE effect. This paper will better reveal how
      the anti-ASE cap suppresses the ASE effect.

PMID- 29047564
TI  - Zonal wavefront reconstruction in quadrilateral geometry for phase measuring
      deflectometry.
AB  - There are wide applications for zonal reconstruction methods in slope-based
      metrology due to its good capability of reconstructing the local details on
      surface profile. It was noticed in the literature that large reconstruction
      errors occur when using zonal reconstruction methods designed for rectangular
      geometry to process slopes in a quadrilateral geometry, which is a more general
      geometry with phase measuring deflectometry. In this work, we present a new idea
      for the zonal methods for quadrilateral geometry. Instead of employing the
      intermediate slopes to set up height-slope equations, we consider the height
      increment as a more general connector to establish the height-slope relations for
      least-squares regression. The classical zonal methods and interpolation-assisted
      zonal methods are compared with our proposal. Results of both simulation and
      experiment demonstrate the effectiveness of the proposed idea. In implementation,
      the modification on the classical zonal methods is addressed. The new methods
      preserve many good aspects of the classical ones, such as the ability to handle a
      large incomplete slope dataset in an arbitrary aperture, and the low
      computational complexity comparable with the classical zonal method. Of course,
      the accuracy of the new methods is much higher when integrating the slopes in
      quadrilateral geometry.

PMID- 29047565
TI  - Polarization property changes of optical beam transmission in atmospheric
      turbulent channels.
AB  - We theoretically analyze and experimentally verify the performance of multiple
      polarization parameters in the presence of atmospheric turbulence for a
      terrestrial optical transmission. First, both the first- and second-moment
      characteristic of polarization parameters are derived based on the extended
      Huygens-Fresnel principle. Then, numerical simulations are presented for
      different propagating distances, optical source properties, and turbulent
      strengths. Finally, a series of well-designed experiments are carried out to
      verify the theory with turbulence-controlled conditions, where the polarization
      states are measured at two wavelengths, respectively. As a result, the
      theoretical predictions conform closely to the experimental data, and both show
      that with the increasing turbulent strength, the first-order moment of
      polarization parameters varies in different trends, while their second-order
      moment increases. The proposed approach is promising for building a comprehensive
      statistical model of polarization and improving the performance of a free-space
      optical communication link.

PMID- 29047566
TI  - Infrared optical constants of liquid palm oil and palm oil biodiesel determined
      by the combined ellipsometry-transmission method.
AB  - The optical constants of vegetable oils and biodiesels are the basic input
      parameters in the study of the thermal radiation transfer and monitoring the
      productivity of vegetable oils converting to biodiesels. In this work, a combined
      ellipsometry-transmission method is presented to obtain the optical constants of
      palm oil and palm oil biodiesel between 20 degrees C and 150 degrees C in the
      spectral range 600-4100  cm-1 and to study the temperature effect on the optical
      constants. In the combined method, a modified ellipsometry method is used to
      measure the optical constants of palm oil and palm oil biodiesel for the whole
      researched wave bands. For the weak absorption regions in which the ellipsometry
      method cannot give precise absorption indices, the transmission method is
      conducted to get the absorption indices using the refractive indices obtained by
      the proposed ellipsometry method. Deionized water and methanol are taken as
      examples to verify the combined ellipsometry-transmission method. It is shown
      that the combined method can overcome the deficiencies of the traditional
      ellipsometry and transmission method, which can be used for the measurements of
      both strong and weak absorption wave bands. The experimental analyses indicate
      that temperature exerts a noticeable influence on the infrared optical constants
      of palm oil and palm oil biodiesel. With the increase of temperature, the
      refractive indices at certain wavenumbers decrease nearly linearly, and the
      amplitudes of dominant absorption peaks show a decreasing trend. The absorption
      peaks located around 3550  cm-1 show blueshift trends as temperature increases.
      Comparing these two kinds of oils, palm oil presents larger values in refractive
      indices and dominant absorption peaks.

PMID- 29047567
TI  - Lateral mode constrictions for broad-ridge quantum cascade lasers.
AB  - We develop a method for analyzing the lateral modes of broad-ridge quantum
      cascade lasers (QCLs) that incorporate an intracavity lateral constriction. The
      calculations provide results that are in good agreement with the recent data
      taken on broad-ridge QCLs that incorporate such lateral constrictions. We
      conclude by providing design principles for broad-ridge QCLs that implement an
      intracavity lateral constriction.

PMID- 29047568
TI  - Characteristics of chiral long-period fiber gratings written in the twisted two
      mode fiber by CO2 laser.
AB  - We demonstrated the fabrication of a chiral long-period grating (CLPG) by
      twisting a two-mode fiber (TMF) when a CO2 laser beam was sweeping along the
      fiber axis. The torsion, temperature, and surrounding refractive index
      characteristics of the fabricated TMF-CLPG were investigated experimentally. The
      fabricated TMF-CLPG has a high torsion sensitivity [0.7768 nm/(rad/m)], and can
      measure the twist rate and twist direction simultaneously. This kind of CLPG
      would have great potential applications in high-sensitivity optical sensors.

PMID- 29047569
TI  - Temporal evolution of low-coherence reflectrometry signals in photoacoustic
      remote sensing microscopy.
AB  - Recently, a new noncontact reflection-mode imaging modality called photoacoustic
      remote sensing (PARS) microscopy was introduced providing optical absorption
      contrast. Unlike previous modalities, which rely on interferometric detection of
      a probe beam to measure surface oscillations, the PARS technique detects
      photoacoustic initial pressures induced by a pulsed laser at their origin by
      monitoring intensity modulations of a reflected probe beam. In this paper, a
      model describing the temporal evolution from a finite excitation pulse is
      developed with consideration given to the coherence length of the interrogation
      beam. Analytical models are compared with approximations, finite-difference time
      domain (FDTD) simulations, and experiments with good agreement.

PMID- 29047570
TI  - Three-dimensional shape profiling by out-of-focus projection of colored pulse
      width modulation fringe patterns.
AB  - Three-dimensional (3D) shape profiling by sinusoidal phase-shifting methods is
      affected by the non-linearity of the projector. To overcome this problem, the
      defocusing technique has become an important alternative to generate sinusoidal
      fringe patterns. The precision of this method depends on the binary pattern used
      and on the defocusing applied. To improve the defocusing technique, we propose
      the implementation of a color-based binary fringe patterns. The proposed
      technique involves the generation of colored pulse width modulation (PWM) fringe
      patterns, which are generated with different frequencies at the carrier signal.
      From an adequate selection of these frequencies, the colored PWM fringe patterns
      will lead to amplitude harmonics lower than the conventional PWM fringe patterns.
      Hence, the defocusing can decrease, and the 3D shape profiling can be more
      accurate. Numerical simulations and experimental results are presented as
      validation.

PMID- 29047571
TI  - Application of a mobile laser-induced breakdown spectroscopy system to detect
      heavy metal elements in soil.
AB  - In this work, a mobile laser-induced breakdown spectroscopy (LIBS) system has
      been successfully applied to in situ analysis of heavy metals in soil samples.
      The LIBS system had two working methods, which were a fixed measuring method and
      a handheld method. For the fixed measuring method, a simple sample pretreatment
      was needed to reduce the soil matrix effect generated by moisture and porosity.
      Experiments proved that this method could be used to semi-quantitatively detect
      heavy metals when combined with the traditional calibration curve method. The
      limits of detection for copper, lead, and zinc were all below 10  mg/kg, which
      satisfied the need of heavy metal detection in soil. Principal component analysis
      was used for soil classification, which helped to build appropriate calibration
      curves. On the basis of soil classification, accurate and rapid detection of
      heavy metals in soil is feasible. For the handheld method, spectrum intensity and
      stability decreased significantly compared with the fixed measuring method.
      However, by using the internal standard method, the stability of LIBS data was
      improved significantly to 6%. For soil samples with serious heavy-metal
      pollution, the measurement errors were less than 12%, which indicated that
      handheld LIBS was effective to monitor heavy-metal pollution in soil. The
      research results provide application support for rapid and on-site monitoring of
      heavy metals in soil.

PMID- 29047572
TI  - CHARM-F-a new airborne integrated-path differential-absorption lidar for carbon
      dioxide and methane observations: measurement performance and quantification of
      strong point source emissions.
AB  - The integrated-path differential-absorption lidar CHARM-F (CO2 and CH4 Remote
      Monitoring-Flugzeug) was developed for the simultaneous measurement of the
      greenhouse gases CO2 and CH4 onboard the German research aircraft HALO (High
      Altitude and Long Range Research Aircraft). The purpose is to derive the
      weighted, column-averaged dry-air mixing ratios of the two gases with high
      precision and accuracy between aircraft and ground or cloud tops. This paper
      presents the first measurements, performed in the spring of 2015, and shows
      performance analyses as well as the methodology for the quantification of strong
      point sources applied on example cases. A measurement precision of below 0.5% for
      20 km averages was found. However, individual measurements still show deviations
      of the absolute mixing ratios compared to corresponding data from in situ
      profiles. The detailed analysis of the methane point source emission rate yields
      plausible results (26+/-3  m3/min or 9.2+/-1.15  kt CH4 yr-1), which is in good
      agreement with reported numbers. In terms of CO2, a power plant emission could be
      identified and analyzed.

PMID- 29047573
TI  - Microscanning in Hadamard spectroscopy.
AB  - Hadamard spectroscopy is a method of taking spectroscopic measurements suited to
      domains such as far infrared, where the sensor noise is dominant. Unfortunately,
      the signal-to-noise ratio of such a system scales poorly with the resolution. In
      this paper, we analyze a technique called microscanning that attempts to solve
      this problem by combining several lower resolution "preview" spectra to form a
      higher resolution spectrum. We provide a theoretical analysis of the method
      concerning the noise reduction and blurring. We conduct simulations based on the
      measured far infrared spectra of minerals in order to determine if the noise
      reduction can outweigh the loss in accuracy caused by the blurring effect, and we
      demonstrate the microscanning method in experimental conditions. We conclude that
      the microscanning method provides a noise reduction by a factor proportional to
      the number of previews and that it can be useful in far infrared spectroscopy.

PMID- 29047574
TI  - Grating interferometer for light-efficient spatial coherence measurement of
      arbitrary sources.
AB  - We present a theoretical analysis and experimental verification of a z-scanning
      double-grating interferometer for spatial coherence measurements in space
      frequency and space-time domains. This interferometer permits the measurement of
      spatial coherence between an arbitrary pair of points along a one-dimensional
      line, and in favorable conditions, it has a high light efficiency compared to the
      classical Young's two-pinhole experiment. The scheme is applicable to both quasi
      monochromatic and broadband sources that need not obey the Schell model. We first
      provide experimental results with several narrowband primary and secondary
      sources, and then apply the technique to broadband sources with discrete and
      continuous spectra. In the latter case, the complex degree of (time-domain)
      spatial coherence is retrieved from spectrally resolved measurements using the
      Friberg-Wolf theorem [Opt. Lett.20, 623 (1995)OPLEDP0146
      959210.1364/OL.20.000623]. We compare all results to those obtained with Young's
      interferometer realized using a digital micromirror device.

PMID- 29047575
TI  - Inversion of oceanographic profiling lidars by a perturbation to a linear
      regression.
AB  - We present a simple, robust inversion for airborne oceanographic lidar profiles.
      A linear regression to the logarithm of the return is followed by a perturbation
      to obtain a backscatter estimate. For typical thin plankton layer examples,
      errors are expected to be <10% over 90% of the ocean. The inversion was applied
      to lidar data off the coast of Florida, where the correlation between lidar
      backscatter at 5 m and surface chlorophyll concentration from satellite ocean
      color measurements was 0.92.

PMID- 29047576
TI  - Modeling of light-emitting diode wavefronts for the optimization of transmission
      holograms.
AB  - The objective of applying transmission holograms in automotive headlamp systems
      requires the adaptation of holograms to divergent and polychromatic light sources
      like light-emitting diodes (LEDs). In this paper, four different options to
      describe the scalar light waves emitted by a typical automotive LED are regarded.
      This includes a new approach to determine the LED's wavefront from
      interferometric measurements. Computer-generated holograms are designed
      considering the different LED approximations and recorded into a photopolymer.
      The holograms are reconstructed with the LED and the resulting images are
      analyzed to evaluate the quality of the wave descriptions. In this paper, we show
      that our presented new approach leads to better results in comparison to other
      wave descriptions. The enhancement is evaluated by the correlation between
      reconstructed and ideal images. In contrast to the next best approximation, a
      spherical wave, the correlation coefficient increased by 0.18% at 532 nm, 1.69%
      at 590 nm, and 0.75% at 620 nm.

PMID- 29047577
TI  - Experimental demonstration of nonlinear enhancement in a graphene-deposited
      microfiber.
AB  - Nonlinear enhancement is experimentally demonstrated by depositing graphene
      scraps from graphene ethanol dispersion onto a tapered microfiber. The
      enhancement of the nonlinearity is verified by observing the four-wave mixing
      (FWM) effect in the homemade graphene-deposited microfiber (GDMF). When the
      incident pump power is 24.2 dBm, the FWM conversion efficiency in the GDMF
      reaches -57.1  dB. Compared to the bare microfiber with the same dimensions, the
      conversion efficiency is improved by more than 3 dB. Our fabricated GDMF provides
      a simple way to enhance the fiber nonlinearity, and it will be suitable for
      nonlinear applications such as wavelength conversion and other optical signal
      processing operations.

PMID- 29047578
TI  - Calculation model of the Hyperion reflected light scattering efficiency.
AB  - Space-borne sensors can provide valuable spatial image data, which play an
      irreplaceable role in ground target observation. In this paper, we have derived a
      parameter called the scattering efficiency per unit area (SEA), which is used to
      describe the ability of different media to change the energy of an incident field
      in the far zone. Over the range of Hyperion wavelengths, the SEA are unequal,
      which can be used as the characteristic signal for target classification. In
      order to increase the accuracy of this model, we selected five groups of
      characteristic bands unaffected by noise using principal component analysis. We
      then combined this with a backpropagation neural network; the identification of
      five ground media was implemented, and the residuals were very low. These
      theoretical and experimental analyses verify that SEA can be used as the basis
      for studying the physical characteristics of scattering of ground targets.

PMID- 29047579
TI  - Experimental power spectral density analysis for mid- to high-spatial frequency
      surface error control.
AB  - The control of surface errors as a function of spatial frequency is critical
      during the fabrication of modern optical systems. A large-scale surface figure
      error is controlled by a guided removal process, such as computer-controlled
      optical surfacing. Smaller-scale surface errors are controlled by polishing
      process parameters. Surface errors of only a few millimeters may degrade the
      performance of an optical system, causing background noise from scattered light
      and reducing imaging contrast for large optical systems. Conventionally, the
      microsurface roughness is often given by the root mean square at a high spatial
      frequency range, with errors within a 0.5*0.5  mm local surface map with 500*500
      pixels. This surface specification is not adequate to fully describe the
      characteristics for advanced optical systems. The process for controlling and
      minimizing mid- to high-spatial frequency surface errors with periods of up to ~2
      3  mm was investigated for many optical fabrication conditions using the measured
      surface power spectral density (PSD) of a finished Zerodur optical surface. Then,
      the surface PSD was systematically related to various fabrication process
      parameters, such as the grinding methods, polishing interface materials, and
      polishing compounds. The retraceable experimental polishing conditions and
      processes used to produce an optimal optical surface PSD are presented.

PMID- 29047580
TI  - Diffraction by gratings with random fill factor.
AB  - In this work, we analyze the diffraction produced by Ronchi gratings where the
      fill factor is not constant, but presents random fluctuations around its nominal
      value. This effect can be produced while developing the grating with etchers
      since the process can be slightly unpredictable. We obtain the theoretical
      formalism to describe the intensity produced by the grating at near and far
      field, showing that smoothing of the self-images is produced at the near field
      and, consequently, cancellation of higher diffraction orders is obtained at the
      far field. In addition, different nominal fill factors produce different
      diffraction behaviors in terms of the randomness. We corroborate the analytical
      formalism using a direct integration method based on the Rayleigh-Sommerfeld
      formula and conclude that the numerical results are in high agreement with the
      theoretical predictions.

PMID- 29047581
TI  - Optimum selection of detection point and threshold noise ratio of airborne
      infrared search and track systems.
AB  - To improve the recognition probability of airborne infrared search and track
      systems (IRSTS) in air-to-air operations, the point target recognition
      probability model is established. And using an operating range model, the
      detection envelope is calculated for the airborne IRSTS. Combining with different
      operational backgrounds and specific technical parameters, the simulation results
      show that: (1) an increase in visual range and target speed, along with a
      decrease of oblique angle, produces an increase in the recognition probability;
      (2) the angle of maximum operating range of each detection envelope is the
      optimum detection point for the airborne IRSTS; and (3) the optimum threshold
      noise ratio is 8-10. These conclusions provide further scope in improving the
      operational effectiveness of airborne IRSTS in practical applications.

PMID- 29047582
TI  - Composite infrared spectrometer (CIRS) on Cassini.
AB  - The Cassini spacecraft orbiting Saturn carries the composite infrared
      spectrometer (CIRS) designed to study thermal emission from Saturn and its rings
      and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of
      the payload providing unique measurements and important synergies with the other
      instruments. It takes full advantage of Cassini's 13-year-long mission and
      surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The
      instrument, consisting of two interferometers sharing a telescope and a scan
      mechanism, covers over a factor of 100 in wavelength in the mid and far infrared.
      It is used to study temperature, composition, structure, and dynamics of the
      atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of
      the icy moons. CIRS has returned a large volume of scientific results, the
      culmination of over 30 years of instrument development, operation, data
      calibration, and analysis. As Cassini and CIRS reach the end of their mission in
      2017, we expect that archived spectra will be used by scientists for many years
      to come.

PMID- 29047583
TI  - Using confidence intervals to evaluate the focus alignment of spectrograph
      detector arrays.
AB  - High-resolution spectrographs extract detailed spectral information of a sample
      and are frequently used in astronomy, laser-induced breakdown spectroscopy, and
      Raman spectroscopy. These instruments employ dispersive elements such as prisms
      and diffraction gratings to spatially separate different wavelengths of light,
      which are then detected by a charge-coupled device (CCD) or complementary metal
      oxide-semiconductor (CMOS) detector array. Precise alignment along the optical
      axis (focus position) of the detector array is critical to maximize the
      instrumental resolution; however, traditional approaches of scanning the detector
      through focus lack a quantitative measure of precision, limiting the
      repeatability and relying on one's experience. Here we propose a method to
      evaluate the focus alignment of spectrograph detector arrays by establishing
      confidence intervals to measure the alignment precision. We show that propagation
      of uncertainty can be used to estimate the variance in an alignment, thus
      providing a quantitative and repeatable means to evaluate the precision and
      confidence of an alignment. We test the approach by aligning the detector array
      of a prototype miniature echelle spectrograph. The results indicate that the
      procedure effectively quantifies alignment precision, enabling one to objectively
      determine when an alignment has reached an acceptable level. This quantitative
      approach also provides a foundation for further optimization, including automated
      alignment. Furthermore, the procedure introduced here can be extended to other
      alignment techniques that rely on numerically fitting data to a model, providing
      a general framework for evaluating the precision of alignment methods.

PMID- 29047584
TI  - Method of first-order analysis of a three-element two-conjugate zoom lens.
AB  - A method is described for the first-order analysis of a two-conjugate zoom lens
      composed of three movable elements. Such an optical system satisfies the
      requirement that the object, image, and pupil planes are fixed within the change
      of its magnification. General formulas are derived for the calculation of
      parameters of a three-component two-conjugate zoom lens system, which enable us
      to calculate the optical power of individual optical elements and their distances
      for a different range of magnification and imposed conditions. The application of
      derived formulas is presented on three examples of optical systems with different
      parameters.

PMID- 29047585
TI  - Optical modulation format conversion from one QPSK to one BPSK with information
      integrity-employing phase-sensitive amplifier.
AB  - In this paper, a scheme for optical modulation format conversion from one 20 Gbps
      quadrature phase-shift keying (QPSK) signal to one 20 Gbps binary phase-shift
      keying (BPSK) signal with information integrity is proposed and verified by
      simulation. The theory of degenerate phase-sensitive amplifier (PSA) employed as
      a phase de-multiplexer is derived in detail and used to decompose the in- (I) and
      quadrature- (Q) phase components of QPSK. Then the I and Q components are
      parallel-to-series converted into one BPSK. The constellations show that the
      phase noise of the original signal is effectively restrained by the conversion
      system through use of the PSA. The error vector magnitude and bit-error rate
      (BER) of the QPSK, converted BPSK, and a back-to-back BPSK are measured and
      compared with each other. We find that the BER performance of the converted BPSK
      is better than QPSK and maintains the original information integrity with
      different input signal quality. Some potential issues are also discussed as to
      practical implementation of the scheme. This modulation-format-conversion scheme
      has potential applications in improving the signal BER performance and flexible
      transmitters and receivers in software-defined networks.

PMID- 29047586
TI  - Beam-steering efficiency optimization method based on a rapid-search algorithm
      for liquid crystal optical phased array.
AB  - A rapid-search algorithm to improve the beam-steering efficiency for a liquid
      crystal optical phased array was proposed and experimentally demonstrated in this
      paper. This proposed algorithm, in which the value of steering efficiency is
      taken as the objective function and the controlling voltage codes are considered
      as the optimization variables, consisted of a detection stage and a construction
      stage. It optimized the steering efficiency in the detection stage and adjusted
      its search direction adaptively in the construction stage to avoid getting caught
      in a wrong search space. Simulations had been conducted to compare the proposed
      algorithm with the widely used pattern-search algorithm using criteria of
      convergence rate and optimized efficiency. Beam-steering optimization experiments
      had been performed to verify the validity of the proposed method.

PMID- 29047587
TI  - Lensless complex amplitude image retrieval through a visually opaque scattering
      medium.
AB  - We propose and experimentally demonstrate lensless complex amplitude image
      retrieval through a visually opaque scattering medium from spatially fluctuating
      fields using intensity measurement and a phase-retrieval algorithm. The complex
      amplitude information of the hidden object is encoded in the form of a real and
      nonnegative amplitude function represented as an interference pattern. A single
      charge coupled device (CCD) image of the scattered light collected through a
      visually opaque optical diffuser contains enough information to digitally
      regenerate the interference pattern. Furthermore, a lensless configuration is
      implemented which eliminates any possible aberration effects associated with
      optical components, and this further has promising applications where the use of
      imaging optics is not feasible. Experimental results for the recovery of complex
      fields corresponding to optical vortices of two different topological charges are
      presented.

PMID- 29047588
TI  - Range extension of the optical delay line in white light interferometry.
AB  - We propose an effective and promising method to extend the continuous range of
      the optical delay line in white light interferometry. The method adopts the
      combination of switchable fixed delays and a continuous-scanning stage laid in
      one arm of the interferometer. Moreover, a fiber ring constructed by a fiber
      coupler is employed in the other arm to achieve self-calibration and improve the
      delay precision, voiding the use of a specialized measurement instrument. The
      range-extension method maintains the original performances of the stage just
      through the process of orderly copying and jointing. The setup with 16 parallel
      fixed delay paths is experimentally demonstrated. The insertion loss of the
      optical delay line will not increase as the range extension and keeps an average
      of 1.45 dB with a fluctuation of +/-0.15  dB(3sigma) over a delay range of 37.2 m
      without a blind zone. In addition, the delay precision as a function of the port
      number of the optical switch does not deteriorate and remains at a level of 10.21
      MUm with a standard deviation of 0.08 MUm. The loss and delay precision features
      enable the proposed structure to be extended without limitation, which is
      particularly significant for practical applications.

PMID- 29047589
TI  - Design, fabrication, and testing of zone-plate interconnects for a compact
      optoelectronic integrated neural coprocessor.
AB  - We have designed, fabricated, and tested a set of scalable compact optical
      elements for use in the compact optoelectronic integrated neural (COIN)
      coprocessor. The COIN coprocessor is an implementation of a feed-forward neural
      network that uses optical interconnects to transmit information from one layer of
      neurons to the next. Optical interconnection elements based on Fresnel-zone-plate
      concepts have been fabricated using standard lithographic processes, thereby
      allowing large arrays to be fabricated with a single exposure. This paper
      discusses the design trade-offs that must be considered for effective use of such
      elements in a COIN coprocessor, and the fabrication and testing of a set of such
      optical interconnection elements. It was found that the behavior of the
      fabricated zone plates correlated well with the design simulation, and that this
      type of optical element is indeed suitable for use in the COIN coprocessor.

PMID- 29047590
TI  - Correcting aero-optical wavefront aberration of the supersonic mixing layer based
      on periodic pulse forcing.
AB  - A correction strategy for correcting the aero-optical wavefront aberration of the
      supersonic mixing layer is presented based on flow control that is implemented by
      periodic pulse forcing. The flow field of the controlled supersonic mixing layer
      is simulated by large eddy simulation, and the optical transmission trajectory of
      the incident beam is computed by the ray-tracing method. The key component of the
      correction strategy is a compensation signal employed to correct the aberrated
      wavefront, which is produced according to flow and control parameters. Three
      numerical examples, including cases of an incident beam at different streamwise
      locations, flow control with different pulse periods, and vortex evolution in a
      pulse period, are performed to test performance of the correction strategy. The
      numerical results indicate that the correction strategy has a great effect in
      perfecting the aberrated wavefront again, and hence the far-field beam quality is
      also improved remarkably. In the end, the possibility of experimental
      implementation of the presented correction strategy is discussed.

PMID- 29047591
TI  - Ethics, plagiarism, and Crosscheck: editorial.
AB  - Editor-in-Chief Ron Driggers discusses common ways that articles can include
      plagiarism and how to avoid them.

PMID- 29047592
TI  - Digital holography on moving objects: interference contrast as a function of
      velocity and aperture width.
AB  - Digital holographic measurements on planar moving objects are investigated. We
      discuss the dependence of the interference contrast on velocity and aperture
      width for both diffusely and specularly reflecting objects. Using spatial phase
      shifting, the experimental results for motion in parallel and perpendicular to
      the optical axis are in good agreement with the theoretical considerations.
      Measurements with object velocities of up to 100 mm/s are conducted using only
      less than 1 mW of continuous-wave laser light. These considerations are used to
      determine the optimal angle between the direction of motion and the illuminating
      beam, resulting in the lowest decrease in contrast with increasing velocity.

PMID- 29047593
TI  - Influence of a variable Rayleigh scattering-loss coefficient on the light
      backscattering in multimode optical fibers.
AB  - The recently developed diffraction technique of analytical investigation of the
      Rayleigh backscattering produced by an incident fundamental mode in a multimode
      optical fiber with an arbitrary refractive index profile is supplemented by
      taking into account the Rayleigh scattering-loss coefficient, which could be
      variable within the fiber cross section. The relative changes in various radial
      and azimuthal modes' excitation levels, due to some typical radial dependences of
      this coefficient, are computed for the quadratic- and step-index fibers. It is
      stated that the excitation efficiency could either rise or decay for different
      modes. The effect of the variable Rayleigh scattering-loss coefficient is shown
      to be more noticeable in the fibers with a quadratic refractive index profile,
      whereas it is negligible in actual multimode step-index fibers.

PMID- 29047594
TI  - Calculation of the overlap factor for scanning LiDAR based on the tridimensional
      ray-tracing method.
AB  - The overlap factor is used to evaluate the LiDAR light collection ability.
      Ranging LiDAR is mainly determined by the optical configuration. However,
      scanning LiDAR, equipped with a scanning mechanism to acquire a 3D coordinate
      points cloud for a specified target, is essential in considering the scanning
      effect at the same time. Otherwise, scanning LiDAR will reduce the light
      collection ability and even cannot receive any echo. From this point of view, we
      propose a scanning LiDAR overlap factor calculation method based on the
      tridimensional ray-tracing method, which can be applied to scanning LiDAR with
      any special laser intensity distribution, any type of telescope (reflector,
      refractor, or mixed), and any shape obstruction (i.e., the reflector of a coaxial
      optical system). A case study for our LiDAR with a scanning mirror is carried
      out, and a MATLAB program is written to analyze the laser emission and reception
      process. Sensitivity analysis is carried out as a function of scanning mirror
      rotation speed and detector position, and the results guide how to optimize the
      overlap factor for our LiDAR. The results of this research will have a guiding
      significance in scanning LiDAR design and assembly.

PMID- 29047595
TI  - Ultrafast all-optical flip-flop based on passive micro Sagnac waveguide ring with
      photonic crystal fiber.
AB  - Ultrafast all-optical flip-flop based on a passive micro Sagnac waveguide ring is
      studied through theoretical analysis and numerical simulation in this paper. The
      types of D, R-S, J-K, and T flip-flop are designed by controlling the cross-phase
      modulation effect of lights in this special microring. The high nonlinearity of
      the hollow-core photonic crystal fiber is implanted on a chip to shorten the
      length of the ring and reduce input power. By sensible management, the pulse
      width ratio of the input and the control signal, problems of pulse narrowing, and
      residual pedestal at the out port are solved. The parameters affecting the
      performance of flip-flops are optimized. The results show that the all-optical
      flip-flops have stable performance, low power consumption, high transmission rate
      (up to 100  Gb/s), and response time in picosecond order. The small size
      microwaveguide structure is suitable for photonic integration.

PMID- 29047596
TI  - Design of wafer-bonded structures for near room temperature Geiger-mode operation
      of germanium on silicon single-photon avalanche photodiode.
AB  - We investigate the effect of temperature on the single-photon properties of four
      germanium/silicon (Ge/Si) single-photon avalanche photodiodes (SPADs), which are
      fabricated by Ge-on-Si direct epitaxial growth, Ge-on-Si two-step epitaxial
      growth, Ge/Si direct wafer bonding, and Si/Si hydrophobic bonding, respectively.
      It is found that the wafer-bonded Ge/Si SPAD exhibits extremely low dark current
      and dark count rate (DCR) compared with the epitaxial ones at 250 and 300 K. This
      implies that the wafer-bonding technique is a possible candidate for the
      fabrication of Ge/Si SPAD, which can be operated at near room temperature.
      Additionally, due to the low DCR and high operation temperature, the wafer-bonded
      Ge/Si SPAD shows extremely high pulse repetition rate (~28  MHz in theory for
      DCR=108  Hz). That is, the wafer-bonded Ge/Si SPAD can be used in a high-speed
      field. Finally, the effect of voltage pulse width, number of photons per pulse,
      and hold-off time on the performance of the wafer-bonded Ge/Si SPAD at different
      temperatures is also clarified.

PMID- 29047597
TI  - Investigation on a laser-assisted radiation thermometry technique.
AB  - A laser-assisted radiation thermometry (LART) technique is proposed for the
      surface temperature measurement of objects at high temperatures, which obviates
      the need for the knowledge of specimen emissivity. It uses a modulated laser to
      excite a temperature rise at the specimen surface, which is remotely sensed
      through thermal radiation detection at two infrared wavelengths. The theoretical
      analysis indicates that the surface temperature of the specimen can be inferred
      from the detected signals, independently of specimen emissivity. Measurements
      were performed on an oxidized Inconel 600 sample over a temperature range of 1120
      1265 K. Measured surface temperatures were compared with those deduced from
      thermocouple measurements made inside the sample, and indicated less than 3%
      differences between them for sample surface temperatures above 1200 K.

PMID- 29047598
TI  - Optimal parameter retrieval for metamaterial absorbers using the least-square
      method for wide incidence angle insensitivity.
AB  - In this paper, we propose a specific algorithm based on the least-square method
      to predict the incidence angle insensitivity of a metamaterial absorber. The
      proposed algorithm was analyzed on a metamaterial absorber design with circular
      sectors on the top layer and a full copper cover on the bottom layer. We
      retrieved the parameters of inductance, capacitance, and conductance from the
      equivalent circuit of the metamaterial absorber at different incidence angles of
      0 degrees , 30 degrees , 65 degrees , and 70 degrees  under both transverse
      electric and transverse magnetic polarization. The complex impedances calculated
      from the optimal parameter retrieval are compared with the complex impedances
      from full-wave simulation at each incidence angle. The calculated and simulated
      results show excellent agreement, and the proposed algorithm can be used to
      design angle-insensitive metamaterial absorbers.

PMID- 29047600
TI  - On-chip splicer for coupling light between photonic crystal and solid-core
      fibers.
AB  - We present a lithographically defined, ultra-high vacuum (UHV) compatible on-chip
      structure acting as a mechanical splicer that allows efficient injection of light
      from a conventional solid-core (SC) fiber to a hollow-core photonic crystal fiber
      (HCPCF) and vice versa. We report the observed coupling efficiencies for an
      assortment of solid-core fibers and a HCPCF with maximum efficiency between solid
      core fiber and HCPCF of 93%.

PMID- 29047599
TI  - Temperature sensing using CdSe quantum dot doped poly(methyl methacrylate)
      microfiber.
AB  - This work describes noncontact temperature measurements using wavelength shifts
      of CdSe quantum dot (QD) doped poly(methyl methacrylate) microfiber. The sensor
      is fabricated using a drawing method by bridging two tapered single mode fibers
      with a polymer microfiber (PMF) approximately 3 MUm in diameter. A set of a PMF
      section with and without the doping of the CdSe-ZnS core-shell QD was applied as
      sensing probes and used to measure temperatures over the range of 25 degrees C-48
      degrees C. The experimental results show that the doped PMF is able to achieve a
      higher performance with a reasonably good sensitivity of 58.5 pm/ degrees C based
      on the wavelength shifting, which is about 18 times that of the undoped PMF
      temperature sensitivity. The proposed sensor showed a linear temperature sensing
      range that matches well with the physiologically relevant temperatures. Moreover,
      these results open the way for long-term and high-stability realization of
      temperature sensing optical fibers.

PMID- 29047601
TI  - Ultrahigh-sensitive temperature sensor based on modal interference in a metal
      under-clad ridge waveguide with a polymer upper cladding.
AB  - We propose a highly sensitive temperature sensor based on modal interference in a
      metal-under-clad ridge waveguide (MUCRW) with polydimethylsiloxane as the upper
      cladding. The proposed sensor exploits the interference between the fundamental
      and the first higher order TE modes of the MUCRW. The increased fractional modal
      power in the ambient medium due to the metal under-cladding along with the high
      thermo-optic coefficient of the upper cladding results in a very significant
      change in the modal characteristics of the two interfering modes with temperature
      variation. Moreover, the effect of temperature change is more pronounced for the
      higher order mode compared with the fundamental mode, resulting in an ultrahigh
      sensitivity of the modal interference to the ambient temperature. The sensitivity
      of the proposed sensor structure is found to be as high as 8.35  nm/ degrees C,
      which, to the best of our knowledge, is the highest reported sensitivity in any
      integrated optic waveguide-based temperature sensor.

PMID- 29047602
TI  - Picosecond nonlinear optical properties of SrTiO3 composite films doped with gold
      and nickel nanoparticles.
AB  - Nanoparticles composite thin films formed by nanometer-sized gold and nickel
      particles embedded in SrTiO3 matrices were fabricated on MgO single-crystal
      substrates by co-depositing the metal and ceramic targets using the pulsed laser
      deposition technique. The linear optical absorption properties were measured from
      350 to 800 nm, and the absorption peak due to the surface plasmon resonance of Au
      metal particles was observed around 557 nm. The ultra-fast third-order nonlinear
      optical properties of the films were determined by a single-beam z-scan method at
      a wavelength of 532 nm with laser duration of 55 ps. The nonlinear refractive
      index n2 and the nonlinear absorption coefficient beta were determined,
      respectively, and the figure of merit chi(3)/alpha (with chi(3) being the third
      order nonlinear susceptibility and alpha the linear optical absorption
      coefficient) was discussed. Whether gold or nickel, metal particles have little
      effect on the figure of merit, but significantly affect the ratio of the real
      part to the imaginary part of chi(3) [Rechi(3)/Imchi(3)]. The obtained
      Rechi(3)/Imchi(3) of Au/SrTiO3 is 1.43, which is more than 3 times as large as
      that of Ni/SrTiO3.

PMID- 29047603
TI  - Performance improvement of coherent free-space optical communication with
      quadrature phase-shift keying modulation using digital phase estimation.
AB  - The performance of coherent free-space optical (CFSO) communication with phase
      modulation is limited by both phase fluctuations and intensity scintillations
      induced by atmospheric turbulence. To improve the system performance, one
      effective way is to use digital phase estimation. In this paper, a CFSO
      communication system with quadrature phase-shift keying modulation is studied.
      With consideration of the effects of log-normal amplitude fluctuations and Gauss
      phase fluctuations, a two-stage Mth power carrier phase estimation (CPE) scheme
      is proposed. The simulation results show that the phase noise can be suppressed
      greatly by this scheme, and the system symbol error rate performance with the two
      stage Mth power CPE can be three orders lower than that of the single-stage Mth
      power CPE. Therefore, the two-stage CPE we proposed can contribute to the
      performance improvements of the CFSO communication system and has determinate
      guidance sense to its actual application.

PMID- 29047604
TI  - Design and implementation of the modified signed digit multiplication routine on
      a ternary optical computer.
AB  - Multiplication with traditional electronic computers is faced with a low
      calculating accuracy and a long computation time delay. To overcome these
      problems, the modified signed digit (MSD) multiplication routine is established
      based on the MSD system and the carry-free adder. Also, its parallel algorithm
      and optimization techniques are studied in detail. With the help of a ternary
      optical computer's characteristics, the structured data processor is designed
      especially for the multiplication routine. Several ternary optical operators are
      constructed to perform M transformations and summations in parallel, which has
      accelerated the iterative process of multiplication. In particular, the routine
      allocates data bits of the ternary optical processor based on digits of
      multiplication input, so the accuracy of the calculation results can always
      satisfy the users. Finally, the routine is verified by simulation experiments,
      and the results are in full compliance with the expectations. Compared with an
      electronic computer, the MSD multiplication routine is not only good at dealing
      with large-value data and high-precision arithmetic, but also maintains lower
      power consumption and fewer calculating delays.

PMID- 29047605
TI  - Chiral long-period gratings: fabrication, highly sensitive torsion sensing, and
      tunable single-band filtering.
AB  - A promising technology for fabricating chiral long-period gratings (CLPGs) is
      demonstrated using a commercial fusion splicer. The key aspect of this technology
      is the incorporation of a fully automatic program we designed for the fusion
      splicer. High-quality CLPGs are successfully fabricated from single-mode fibers,
      which have very flat surfaces and low insertion loss. We also investigate the
      tuning characteristics of the transmission spectrum with the mechanical twist
      rate in CLPGs for torsion sensing application. The torsion sensitivity is
      improved and the shift in resonance wavelength versus the mechanical twist rate
      shows an almost perfect linear relationship. In addition, by choosing appropriate
      fabrication parameters, the fabricated CLPGs can be used as tunable single-band
      rejection filters in a broad wavelength range.

PMID- 29047606
TI  - Neighborhood binary speckle pattern for deformation measurements insensitive to
      local illumination variation by digital image correlation.
AB  - Speckle pattern-based characteristics of digital image correlation (DIC) restrict
      its application in engineering fields and nonlaboratory environments, since
      serious decorrelation effect occurs due to localized sudden illumination
      variation. A simple and efficient speckle pattern adjusting and optimizing
      approach presented in this paper is aimed at providing a novel speckle pattern
      robust enough to resist local illumination variation. The new speckle pattern,
      called neighborhood binary speckle pattern, derived from original speckle
      pattern, is obtained by means of thresholding the pixels of a neighborhood at its
      central pixel value and considering the result as a binary number. The efficiency
      of the proposed speckle pattern is evaluated in six experimental scenarios.
      Experiment results indicate that the DIC measurements based on neighborhood
      binary speckle pattern are able to provide reliable and accurate results, even
      though local brightness and contrast of the deformed images have been seriously
      changed. It is expected that the new speckle pattern will have more potential
      value in engineering applications.

PMID- 29047607
TI  - Aluminum oxide nanoparticles as saturable absorber for C-band passively Q
      switched fiber laser.
AB  - We report on aluminum oxide nanoparticles (Al2O3 NPs) as a saturable absorber
      (SA) for passively Q-switched erbium-doped fiber laser (EDFL) operating at a
      wavelength of 1560.6 nm within the C-band region. A thin film of Al2O3-SA was
      prepared using polyvinyl alcohol (PVA) as a host polymer. Very stable pulses with
      a 57.8 KHz repetition rate and 5.6 MUs pulse width at a threshold pump power of
      158 mW were obtained. A 2.8 MUs pulse width, 81 kHz pulse repetition rate, with
      maximum pulse energy of 56.7 nJ at a diode pump power of 330 mW were recorded. To
      the best of the authors' knowledge, this is the first time that a Al2O3-based SA
      has been used to generate a Q-switched EDFL.

PMID- 29047608
TI  - Noise level estimation of BOTDA for optimal non-local means denoising.
AB  - Due to the similarity of Brillouin optical time domain analyzer (BOTDA) signals,
      image denoising could be utilized to remove the noise. However, the performance
      can be much degraded due to inaccurate noise level estimation. By numerical and
      experimental study, we compare the noise level estimation of three different
      methods for BOTDA: calculating the standard deviation (STD) of the measurements,
      a filter-based estimation algorithm, and a patch-based estimation algorithm
      proposed in this paper, which selects weak textured patches of BOTDA signal and
      then estimates noise level using principal component analysis (W-PCA). The
      results show that W-PCA and the mean of STD can accurately estimate the noise
      level, while the filter-based method overestimates the noise level. Nevertheless,
      for BOTDA with distributed amplification, the STD has huge fluctuation along the
      length, while the W-PCA is relatively robust for its global consideration.
      Experimental results of an ultra-long-distance BOTDA prove that the non-local
      means denoising processing based on W-PCA effectively removes the noise of a
      sensing system without signal distortion.

PMID- 29047609
TI  - Optically coherent image formation and denoising using a plug and play inversion
      framework.
AB  - The performance of optically coherent imaging systems can be limited by
      measurement and speckle noise. In this paper, we develop an image formation
      framework for computing the maximum a posteriori estimate of an object's
      reflectivity when imaged using coherent illumination and detection. The proposed
      approach allows for the use of Gaussian denoising algorithms (GDAs), without
      modification, to mitigate the exponentially distributed and signal-dependent
      noise that occurs in coherent imaging. Several GDAs are compared using both
      simulated and experimental data. The proposed framework is shown to be robust to
      noise and significantly reduce reconstruction error compared to the standard
      inversion technique.

PMID- 29047610
TI  - Graphene Q-switched Er,Yb:GdAl3(BO3)4 laser at 1550  nm.
AB  - A single-layer graphene saturable absorber is employed for passive Q-switching of
      an Er, Yb:GdAl3(BO3)4 (Er,Yb:GdAB) compact laser, representing the first Er-doped
      oxoborate laser Q-switched by graphene. This laser is based on a c-cut 1.8 at. %
      Er3+, 15 at. % Yb3+:GdAB crystal diode-pumped at 0.976 MUm. It generates a
      maximum average output power of 360 mW at 1.55 MUm with a slope efficiency of 23%
      (with respect to the incident power). Stable ~1  MUJ/130  ns pulses are achieved
      at a repetition rate of 400 kHz. This result represents, to the best of our
      knowledge, the shortest pulse duration ever achieved in bulk Er lasers Q-switched
      by 2D materials. Graphene is a promising material for generating nanosecond
      pulses at high repetition rates (MHz range) in Er-doped oxoborate lasers emitting
      in the eye-safe range at 1.5-1.7 MUm.

PMID- 29047611
TI  - Evanescent coupling between refillable ring resonators and laser-inscribed
      optical waveguides.
AB  - We investigated theoretically and experimentally the evanescent coupling between
      photonic waveguides of arbitrary shapes and refillable optical ring resonators on
      the same chip. The resonator hosts were designed to facilitate whispering gallery
      modes and etched by using a single-mask standard lithography process, whereas the
      waveguides were imprinted in the proximity of the ring resonator by using 3D
      ultrafast laser-writing technology. Finite element analysis in conjunction with
      coupled-mode theory revealed a coupling Q-factor (QC) of approximately 106. The
      polymer core ring resonator exhibited a loaded Q-factor (QT) as high as 5.4*104
      and a free spectral range (FSR) of 406 pm at a center wavelength of 775 nm. Long
      term stability of the ring resonator was repeatedly tested by examining the
      spectral location of optical resonances and the constancy of Q-factors and FSRs
      under ambient laboratory conditions for 1 month. We recorded consistent Q-factors
      and repeatable FSRs for all measurements. Renewability of the polymer core was
      demonstrated by removing and redepositing the polymer in the cavity, followed by
      measurements of Q-factors and FSRs. This work promises to enable reconfigurable
      and renewable photonic devices for on-chip lasers, 3D integrated optical signal
      processing, chip-scale molecular sensing, and the investigation of new optical
      phenomena.

PMID- 29047612
TI  - Interfacial surface roughness determination by coherence scanning interferometry
      using noise compensation.
AB  - The capability of coherence scanning interferometry has been extended recently to
      include the determination of the interfacial surface roughness between a thin
      film and a substrate when the surface perturbations are less than ~10  nm in
      magnitude. The technique relies on introducing a first-order approximation to the
      helical complex field (HCF) function. This approximation of the HCF function
      enables a least-squares optimization to be carried out in every pixel of the
      scanned area to determine the heights of the substrate and/or the film layers in
      a multilayer stack. The method is fast but its implementation assumes that the
      noise variance in the frequency domain is statistically the same over the scanned
      area of the sample. This results in reconstructed surfaces that contain
      statistical fluctuations. In this paper we present an alternative least-squares
      optimization method, which takes into account the distribution of the noise
      variance-covariance in the frequency domain. The method is tested using results
      from a simulator and these show a significant improvement in the quality of the
      reconstructed surfaces.

PMID- 29047613
TI  - Spherical aberration measurement of a microscope objective by use of calibrated
      spherical particles.
AB  - The purpose of this paper is to characterize the spherical aberration of a
      microscope objective lens by using diffraction light from nanosphere particles.
      The experimental image of the diffraction spot of a nanosphere is fitted with the
      Nijboer-Zernike model to estimate the spherical aberration. The method can easily
      be extended to the measurement of other and higher-order aberrations. Noticeable
      features of this new measurement technique are real-time measurements, simple
      structure, and flexibility, which lead it to measure optical aberrations with a
      good accuracy.

PMID- 29047614
TI  - Investigation of a metamaterial slab lens and an imaging system based on an
      ellipsoidal cavity.
AB  - A slab metamaterial lens with a refractive index of -1 is capable of producing a
      perfect image, since it transfers all the plane waves from the object plane to
      the image plane without creating any distortion in their amplitudes and phases.
      However, its practical implementation encounters several challenges. In this
      paper, a lossless slab metamaterial lens is investigated using the ray-tracing
      technique. We also discuss propagating waves and evanescent waves and investigate
      an imaging system based on an ellipsoidal cavity. It is shown that since an
      ellipsoidal cavity transfers the beams from one of its foci to the other with the
      same amplitude and phase, it acts similarly to a metamaterial slab lens of n=-1.
      Therefore, this structure can be used as a subwavelength resolution imaging
      system. Also, it does not suffer from chromatic aberration, since all the rays
      transmitted from one focus pass through the other independent of the wavelength.
      Another important advantage of this system, compared to metamaterial-based
      superlenses, is that it can operate at any frequency as long as the dimensions of
      the cavity are much larger than the wavelength.

PMID- 29047615
TI  - Optimal micro-mirror tilt angle and sync mark design for digital micro-mirror
      device based collinear holographic data storage system.
AB  - The collinear holographic data storage system (CHDSS) is a very promising storage
      system due to its large storage capacities and high transfer rates in the era of
      big data. The digital micro-mirror device (DMD) as a spatial light modulator is
      the key device of the CHDSS due to its high speed, high precision, and broadband
      working range. To improve the system stability and performance, an optimal micro
      mirror tilt angle was theoretically calculated and experimentally confirmed by
      analyzing the relationship between the tilt angle of the micro-mirror on the DMD
      and the power profiles of diffraction patterns of the DMD at the Fourier plane.
      In addition, we proposed a novel chess board sync mark design in the data page to
      reduce the system bit error rate in circumstances of reduced aperture required to
      decrease noise and median exposure amount. It will provide practical guidance for
      future DMD based CHDSS development.

PMID- 29047616
TI  - Hyperspectral remote sensing image retrieval system using spectral and texture
      features.
AB  - Although many content-based image retrieval systems have been developed, few
      studies have focused on hyperspectral remote sensing images. In this paper, a
      hyperspectral remote sensing image retrieval system based on spectral and texture
      features is proposed. The main contributions are fourfold: (1) considering the
      "mixed pixel" in the hyperspectral image, endmembers as spectral features are
      extracted by an improved automatic pixel purity index algorithm, then the texture
      features are extracted with the gray level co-occurrence matrix; (2) similarity
      measurement is designed for the hyperspectral remote sensing image retrieval
      system, in which the similarity of spectral features is measured with the
      spectral information divergence and spectral angle match mixed measurement and in
      which the similarity of textural features is measured with Euclidean distance;
      (3) considering the limited ability of the human visual system, the retrieval
      results are returned after synthesizing true color images based on the
      hyperspectral image characteristics; (4) the retrieval results are optimized by
      adjusting the feature weights of similarity measurements according to the user's
      relevance feedback. The experimental results on NASA data sets can show that our
      system can achieve comparable superior retrieval performance to existing
      hyperspectral analysis schemes.

PMID- 29047617
TI  - Wide-band supercontinuum generation in mid-IR using polarization maintaining
      chalcogenide photonic quasi-crystal fiber.
AB  - We report a polarization maintaining chalcogenide (ChG) photonic quasicrystal
      fiber (PQF) for wide-band mid-IR (MIR) supercontinuum (SC) generation. The
      numerical demonstration of SC generation in the proposed PQF spans from 2 to 15
      MUm wavelengths for a pulse power of 2 kW. Besides, the proposed PQF offers a
      high birefringence (10-3 to 10-2) from 3.5 to 15 MUm wavelengths and exhibits a
      low confinement loss (10-7 to 10-1) for the wavelengths from 2 to 15 MUm with
      single mode behavior. The proposed Ge11.5As24Se64.5 PQF is designed with zero
      dispersion wavelengths (ZDWs) at 4.33 and 4.46 MUm for X and Y polarized modes
      within the wavelength range of 2-15 MUm. The polarized spectral broadening of the
      continuum is realized for the first time from 2 to 15 MUm using the proposed PQF
      with a length of 8 mm. Hence, the two orthogonally polarized modes allow the high
      degree of freedom in tuning the properties of the SC. Thus, the proposed PQF
      based SC source is a good candidate for applications such as optical sensing,
      frequency metrology, and optical tomography.

PMID- 29047618
TI  - Simple lock-in detection technique utilizing multiple harmonics for digital PGC
      demodulators.
AB  - A simple lock-in detection technique especially suited for digital phase
      generated carrier (PGC) demodulators is proposed in this paper. It mixes the
      interference signal with rectangular waves whose Fourier expansions contain
      multiple odd or multiple even harmonics of the carrier to recover the quadrature
      components needed for interference phase demodulation. In this way, the use of a
      multiplier is avoided and the efficiency of the algorithm is improved. Noise
      performance with regard to light intensity variation and circuit noise is
      analyzed theoretically for both the proposed technique and the traditional lock
      in technique, and results show that the former provides a better signal-to-noise
      ratio than the latter with proper modulation depth and average interference
      phase. Detailed simulations were conducted and the theoretical analysis was
      verified. A fiber-optic Michelson interferometer was constructed and the
      feasibility of the proposed technique is demonstrated.

PMID- 29047619
TI  - High-power lasers for directed-energy applications: reply.
AB  - The comment by Vorontsov and Weyrauch [Appl. Opt.55, 9950 (2016)APOPAI0003
      693510.1364/AO.55.009950] is aimed at rebutting the critiques in Sprangle et al.
      [Appl. Opt.54, F201 (2015)APOPAI0003-693510.1364/AO.54.00F201] and Nelson et al.
      [Appl. Opt.55, 1757 (2016)APOPAI0003-693510.1364/AO.55.001757]. In the comment,
      Vorontsov and colleagues describe their experiments aimed at demonstrating the
      feasibility of coherent combining of lasers on a distant target, using relatively
      low-power lasers and a cooperative retro-reflective target. The Naval Research
      Laboratory has demonstrated the capability to project high power on a distant
      target by making use of an incoherent combining architecture. The proof-of
      concept experiments were performed in a realistic environment without employing
      cooperative targets and without sophisticated adaptive optics instrumentation.

PMID- 29047620
TI  - Quantifying the polarization properties of non-depolarizing optical elements with
      virtual distorting elements: publisher's note.
AB  - This publisher's note amends the author list and Acknowledgments in Appl. Opt.56,
      2589 (2017)APOPAI0003-693510.1364/AO.56.002589.

PMID- 29047621
TI  - Investigation of the local dispersion change in anomalous dispersion microcavity
      and quantitative analysis of the phase-matching in Kerr comb generation.
AB  - We numerically simulate Kerr comb generation in an anomalous dispersion
      microcavity by modal expansion method and demonstrate that the initiation of comb
      generation is affected by the change of local dispersion possibly caused by
      avoided mode crossings. We also quantitatively analyze the instantaneous phase
      matching of different modes and reveal the characteristics of energy distribution
      in different modes in the dynamics of comb generation. We demonstrate that the
      local dispersion change can control the Kerr comb to transform between Type I and
      Type II combs. We also find that local dispersion is closely related to the
      stability of the power of Kerr comb lines, something that can change the
      dynamical state of the system near the Hamiltonian-Hopf bifurcation under an
      anomalous dispersion regime from a quasi-periodic oscillation state to a periodic
      state (Turing patterns).

PMID- 29047622
TI  - Shock-related effects on aero-optical environment for hemisphere-on-cylinder
      turrets at transonic speeds.
AB  - The aero-optical environment around a hemisphere-on-cylinder turret with both
      flat and conformal windows was studied experimentally in flight using the
      Airborne Aero-Optical Laboratory-Transonic for a range of subsonic and transonic
      Mach numbers between 0.5 and 0.8. Above M=0.6, the local shock appeared near the
      top of the turret, causing additional aero-optical distortions at side-looking
      angles. Using time-resolved wavefronts, instantaneous shock locations were
      extracted and analyzed. The mean shock location was found to be near a viewing
      angle, alpha=80  deg for both window types at M=0.7 and 0.8. For M=0.8, the shock
      has a single frequency peak at StD=0.15, the same as for the unsteady separation
      line, indicating a lock-in mechanism between the shock and the separated wake
      region. Analysis of aero-optical distortions in the wake indicated that the wake
      dynamics were beginning to be affected by the shock only at high transonic speed
      of M=0.8 for the conformal-window turret.

PMID- 29047623
TI  - Structural evolution of axial intensity distribution during hot image formation.
AB  - The structural evolution of the axial intensity distribution during hot image
      formation perturbed by a small circular optical obscuration is investigated in
      detail under different conditions. An analytic expression is derived for the
      axial intensity distribution around the conjugate plane by assuming the thickness
      of the nonlinear medium to be infinitely small. In view of the analysis of the
      axial intensity oscillation, the expression can be extensively utilized to
      characterize the intensity maxima for a nonlinear medium with a finite thickness.
      The nonlinear medium thickness and obscuration size both have great influence on
      the magnitudes and distributed features of the intensity maxima, which initially
      vary from multiple ones with comparable intensities to ultimately a maximum of
      one obviously remaining. The reason for this phenomenon is that the nonlinear
      medium acts like a low-pass filter to the scattering field, and optical
      interference exists between the scattering and background field. Furthermore, a
      fixed expression of nonlinear medium thickness and obscuration size is obtained
      to determine the dividing point of the alterations of the hot image intensity
      distribution.

PMID- 29047624
TI  - General filtering method for electronic speckle pattern interferometry fringe
      images with various densities based on variational image decomposition.
AB  - Filtering off speckle noise from a fringe image is one of the key tasks in
      electronic speckle pattern interferometry (ESPI). In general, ESPI fringe images
      can be divided into three categories: low-density fringe images, high-density
      fringe images, and variable-density fringe images. In this paper, we first
      present a general filtering method based on variational image decomposition that
      can filter speckle noise for ESPI fringe images with various densities. In our
      method, a variable-density ESPI fringe image is decomposed into low-density
      fringes, high-density fringes, and noise. A low-density fringe image is
      decomposed into low-density fringes and noise. A high-density fringe image is
      decomposed into high-density fringes and noise. We give some suitable function
      spaces to describe low-density fringes, high-density fringes, and noise,
      respectively. Then we construct several models and numerical algorithms for ESPI
      fringe images with various densities. And we investigate the performance of these
      models via our extensive experiments. Finally, we compare our proposed models
      with the windowed Fourier transform method and coherence enhancing diffusion
      partial differential equation filter. These two methods may be the most effective
      filtering methods at present. Furthermore, we use the proposed method to filter a
      collection of the experimentally obtained ESPI fringe images with poor quality.
      The experimental results demonstrate the performance of our proposed method.

PMID- 29047625
TI  - Tolerance of holographic polymer-dispersed liquid crystal memory for gamma-ray
      irradiation.
AB  - The radiation-hardened characteristics of holographic polymer-dispersed liquid
      crystal (HPDLC) memory are discussed in the application for an optically
      reconfigurable gate array. The radiation experiments are conducted using a cobalt
      60 gamma radiation source to examine the tolerance of a 100 Mrad total ionizing
      dose for the HPDLC memory. The optical properties are compared in the conditions
      before and after gamma-ray irradiation for the fabricated HPDLC gratings. The
      effects of gamma-ray irradiation on the internal grating structure are also
      investigated by polarization optical microscopy and scanning electron microscopy
      observations. The HPDLC memory irradiated by a 100 Mrad total ionizing dose
      demonstrates the implementation of the optical reconfiguration in a gate-array
      VLSI.

PMID- 29047626
TI  - Mode properties in metallic and non-metallic plasmonic waveguides.
AB  - Non-metallic plasmonic materials have recently attracted research interest due to
      their adjustable plasmonic material properties and the potential low loss, which
      is important to plasmonic waveguides with ultrahigh mode confinement. In this
      paper, we analyzed the mode properties of four types of plasmonic waveguides
      based on noble metals, aluminum-zinc-oxide (AZO), and TiN, where the propagation
      length and mode size are chosen to compare the figures of merit. It is found that
      AZO has the smallest imaginary part of permittivity in the near-infrared region,
      while AZO waveguides have propagation lengths comparable to those of Cu
      waveguides but shorter than those of Au and Ag waveguides. Furthermore, due to
      the larger real part of permittivities, the mode sizes of the AZO and TiN
      waveguides are smaller than those of the metal waveguides, in particular, for the
      insulator-metal-insulator waveguide and dielectric-loaded plasmonic waveguide.
      AZO/ZnO films with tunable carrier density between 1.8*1017/cm3 and 8.6*1020/cm3
      were grown by pulsed-laser deposition. Metal-like properties, i.e., negative real
      part of permittivity around 1550 nm, were observed, predicting an interesting
      candidate in the plasmonic optical interconnect.

PMID- 29047627
TI  - Detecting the topological charge of optical vortex beams using a sectorial
      screen.
AB  - We demonstrate a new method to detect the vortex beams carrying orbital angular
      momentum by a sectorial screen. When the sectorial screen is illuminated by
      optical vortex beams, the far-field diffraction pattern can be used to visually
      determine the modulus and sign of topological charges. We also prove that center
      alignment is not strictly required. The experimental results agree well with the
      simulated results.

PMID- 29047628
TI  - Towards industrial ultrafast laser microwelding: SiO2 and BK7 to aluminum alloy.
AB  - We report systematic analysis and comparison of ps-laser microwelding of industry
      relevant Al6082 parts to SiO2 and BK7. Parameter mapping of pulse energy and
      focal depth on the weld strength is presented. The welding process was found to
      be strongly dependent on the focal plane but has a large tolerance to variation
      in pulse energy. Accelerated lifetime tests by thermal cycling from -50 degrees 
      to +90 degrees C are presented. Welds in Al6082-BK7 parts survive over the full
      temperature range where the ratio of thermal expansion coefficients is 3.4:1.
      Welds in Al6082-SiO2 parts (ratio 47.1:1) survive only a limited temperature
      range.

PMID- 29047629
TI  - Interfaces with fractional optical constants and linear reflectance versus angle
      of incidence for incident unpolarized or circularly polarized light.
AB  - For unpolarized or circularly polarized light incident at a dielectric-conductor
      interface, the intensity reflectance Ru(phi) can be made an essentially linear
      function of the angle of incidence phi over a significant range of phi at
      specific values of the normal-incidence intensity reflectance R0 (~1/3) and the
      associated normal-incidence reflection phase shift delta0 (~40 degrees ). This
      places the complex refractive index n-jk of the interface in the domain of
      fractional optical constants. As demonstrated by specific examples, this is
      realizable in external reflection at vacuum-metal interfaces in the UV, and in
      internal reflection in the IR at interfaces between a transparent high-index
      substrate and an optically opaque thin film of the proper n and k. Fractional
      optical constants are also achievable for light reflection in air at planar
      surfaces of appropriately designed, nanostructured, metamaterial substrates.

PMID- 29047630
TI  - Extended shift-rotation method for absolute interferometric testing of a
      spherical surface with pixel-level spatial resolution.
AB  - An improved shift-rotation method for the absolute testing of spherical surfaces
      is developed to obtain pixel-level spatial resolution and a low noise propagation
      ratio. The absolute testing process includes multiple rotational tests and two
      lateral shifting tests with large shifts. A wavefront reconstruction algorithm
      based on subaperture division and least squares fitting is proposed to
      reconstruct the surface figure of the test optics. Numerical simulation results
      show that the method reveals high-frequency figures missed in the traditional
      Zernike-based shift-rotation method. The algorithm error is lower than 0.4%, and
      the noise propagation ratio can be reduced by 70% using large shifts. The
      absolute testing of spherical optics is carried out to verify this method. One
      spherical surface was tested with the presented absolute testing method and the
      method using a point diffraction interferometer. The difference of the
      measurement results based on the two methods showed that the testing uncertainty
      reached 0.19 nm root mean square (RMS), which indicated that the presented method
      has potential subnanometer testing uncertainty.

PMID- 29047631
TI  - Compact polarization rotator for silicon-based cross-slot waveguides using
      subwavelength gratings.
AB  - A compact and broadband polarization rotator (PR) for silicon-based cross-slot
      waveguides using subwavelength gratings (SWGs) is proposed and analyzed. To
      significantly break the symmetry of the waveguide structure, the diagonal regular
      Si wires of the cross-slot waveguides are replaced with the full etching SWGs.
      Moreover, the special properties of the SWGs-whose effective index is adjustable
      can effectively enhance the modal birefringence between the two lowest-order
      hybrid modes, resulting in a more compact device. By utilizing interference
      effect of the hybrid modes, both transverse electric to transverse magnetic (TE
      to-TM) and TM-to-TE conversion can be efficiently realized. Numerical results
      show that a PR of 12.6 MUm in length at a wavelength of 1.55 MUm is achieved,
      where the polarization conversion efficiency (PCE) and insertion loss (IL) are,
      respectively, 97.2% and 0.71 dB, and the reflection loss is below -20.5  dB for
      both cases. Moreover, a wide bandwidth of ~260  nm for both polarizations is
      obtained for keeping the PCE over 90% and IL below 1 dB. In addition, fabrication
      tolerances to the structural parameters are analyzed in detail, and field
      evolution along the propagation distance is also presented.

PMID- 29047632
TI  - Slip-free processing of (001) silicon wafers under 1064  nm laser ablation.
AB  - Slip phenomenon on a (001) silicon surface under 1064 nm laser ablation was
      studied by experiments and simulations. The surface morphologies of the silicon
      wafers after laser irradiation were observed using an optical microscope. The
      slip patterns showed that slip that occurred before melting was responsible for a
      low-quality ablation surface. The slip damage was predicted by a three
      dimensional finite element model based on heat transfer and thermoelasticity
      theory. The judging criterion of slip was explained in detail. The numerical
      results gave a better understanding of slip phenomenon in experiments. It is
      shown that low laser irradiances cause slip and high laser irradiances are
      helpful in preventing slip. The threshold irradiance is ~1  MW/cm2. Lasers with
      higher irradiance are essential to obtain a slip-free ablation on a (001) silicon
      surface.

PMID- 29047633
TI  - Upconversion photoluminescence of core-shell structured SiO2@YVO4:Yb3+, Er3+,
      Eu3+ nanospheres.
AB  - Core-shell structured SiO2@YVO4:Yb3+, Er3+, Eu3+ nanospheres were prepared by a
      simple solgel method followed by a subsequent heat treatment. The as-prepared
      composites were characterized by a scanning electron microscope, high-resolution
      transmission electron microscope, x-ray diffraction, and photoluminescence
      spectra. The influences of different coating numbers were also studied. To sum
      up, the composites are spherical shaped with an average diameter of 200 nm, and
      the YVO4:Yb3+, Er3+, Eu3+ luminescent particles are successfully coated on the
      surface of SiO2 nanospheres. Under the near-infrared irradiation at 980 nm, the
      composites can emit strong green lights (at 525 nm, 550 nm) attributed to the
      H11/22->I15/24, S3/24->I15/24 transitions of Er3+ ions, and slight red lights (at
      590 nm, 620 nm) attributed to the D05->F17, D05->F27 transitions of Eu3+ ions.
      Given the above, due to the regular core-shell structure, the uniform
      distribution of nanoparticles, and the colorful emissions, the SiO2@YVO4:Yb3+,
      Er3+, Eu3+ nanospheres may have great potential for some biological applications,
      such as biological tracers, bio-labeling, and so on.

PMID- 29047634
TI  - Optical electric field sensor sensitivity direction rerouting and enhancement
      using a passive integrated dipole antenna.
AB  - This work introduces a passive dipole antenna integrated into the packaging of a
      slab-coupled optical sensor to enhance the directional sensitivity of electro
      optic electric field measurements parallel to the fiber axis. Using the passive
      integrated dipole antenna described in this work, a sensor that can typically
      only sense fields transverse to the fiber direction is able to sense a 1.25 kV/m
      field along the fiber direction with a gain of 17.5. This is verified through
      simulation and experiment.

PMID- 29047635
TI  - Key-length analysis of double random phase encoding: publisher's note.
AB  - This publisher's note corrects a value in Table 3 in [Appl. Opt.56, 4474
      (2017)APOPAI0003-693510.1364/AO.56.004474].

PMID- 29047636
TI  - Internal stray radiation measurement for cryogenic infrared imaging systems using
      a spherical mirror.
AB  - Internal stray radiation is a key factor that influences infrared imaging
      systems, and its suppression level is an important criterion to evaluate system
      performance, especially for cryogenic infrared imaging systems, which are highly
      sensitive to thermal sources. In order to achieve accurate measurement for
      internal stray radiation, an approach is proposed, which is based on radiometric
      calibration using a spherical mirror. First of all, the theory of spherical
      mirror design is introduced. Then, the calibration formula considering the
      integration time is presented. Following this, the details regarding the
      measurement method are presented. By placing a spherical mirror in front of the
      infrared detector, the influence of internal factors of the detector on system
      output can be obtained. According to the calibration results of the infrared
      imaging system, the output caused by internal stray radiation can be acquired.
      Finally, several experiments are performed in a chamber with controllable inside
      temperatures to validate the theory proposed in this paper. Experimental results
      show that the measurement results are in good accordance with the theoretical
      analysis, and demonstrate that the proposed theories are valid and can be
      employed in practical applications. The proposed method can achieve accurate
      measurement for internal stray radiation at arbitrary integration time and
      ambient temperatures. The measurement result can be used to evaluate whether the
      suppression level meets the system requirement.

PMID- 29047637
TI  - Minimum length modulator design with a graphene-based plasmonic waveguide.
AB  - In this study, we simulated and analyzed a plasmonic waveguide modulator based on
      a single layer of graphene. It includes a graphene sheet, which sandwiches
      between two layers of silicon dioxide. Then, some gates are arranged on either
      side of the waveguide on a periodic structure. When an electric field is applied
      perpendicular to the waveguide plate, the Fermi level of graphene under the gates
      changes. Detailed analysis is performed by the method of lines based on Maxwell's
      equations along the propagation direction of the waveguide. Computation of the
      multi-gate device starts by examining the effect of the Fermi level. The
      transmission coefficient of the magnetic-field norms of the modulator is
      calculated by varying the parameters, such as Fermi level, length, gates number,
      and distance between the gates to achieve optimized design of the modulator
      device with very small dimensions. The results show that at higher Fermi levels,
      where the imaginary part of the effective index of the waveguide is close to
      zero, the reflection is dominant and absorption is low. Therefore, the modulator
      length becomes so long that it is more than one hundred nanometers. At lower
      Fermi levels, where the amount of the imaginary part of the effective index is
      significant, the absorption is dominant. At this range, a one-gate device is
      sufficient for modulation. Consequently, the designed minimum device length
      becomes equal to six nanometers for the ten-micrometer wavelength. Furthermore,
      the design is carried out in other wavelengths.

PMID- 29047638
TI  - Dual square-wave pulse passively mode-locked fiber laser.
AB  - We study a passively mode-locked square-wave pulse (SWP) fiber laser with a
      nonlinear amplifying loop mirror in the cavity. The net dispersion of the cavity
      is about 0.68  ps2 and the SWP mode-locked fiber laser can be realized. The peak
      power of the SWP hardly varies and the pulse duration gets expanded with the
      increasing pump power. SWPs breaking in the low nonlinear cavity can be observed
      and the stable dual SWP can be achieved in the experiment. When the total pump
      power stays at 800 mW, the interval of dual pulses is 41 ns. The widths of dual
      SWPs are both 1.5 ns. The output power rises linearly with the increasing of the
      pump power, while the interval of dual SWPs is almost constant. Then, the
      physical mechanism of the SWP breaking and vector nature of the pulse are
      analyzed.

PMID- 29047639
TI  - Adaptive reconstruction for coded aperture temporal compressive imaging.
AB  - This paper presents an adaptive reconstruction method for coded aperture temporal
      compressive imaging. A pixel-wise equal-exposure coding strategy is first
      implemented to induce speckle-like features in the moving area of the measured
      image. A moving area detection method is then proposed to reconstruct the
      adaptively segmented moving areas into a series of video frames, which are filled
      back into the stationary clear background. Both simulation and experimental
      results demonstrate that the proposed method significantly reduces the time
      consumption of video reconstruction without degradation of image quality.

PMID- 29047640
TI  - Bicontinuity analysis of multibeam interference three-dimensional periodic
      structures: volume fractions and interface areas.
AB  - Bicontinuous structures are an important subset of three-dimensional periodic
      structures. In multibeam interference structures, the conditions for bicontinuity
      depend on the beam parameters and the exposure dose. As described in the present
      work, these conditions can be applied to establish the range of bicontinuity for
      any multibeam-interference-produced structure. In addition to the bicontinuity
      range, the analysis yields the volume fraction of the constituent materials and
      the normalized interface areas. This analysis has been performed for rhombohedral
      and woodpile lattices as well as their cubic structure limiting cases. A sphere
      at-each-lattice-site model for each of the cubic cases has also been developed
      for comparison. The multibeam interference structures were investigated for
      representative media and for various incident polarizations.

PMID- 29047641
TI  - Efficient generation of vector beams by calibrating the phase response of a
      spatial light modulator.
AB  - The spatial light modulator (SLM) is considered as an effective device to create
      beams with inhomogeneous phases and polarizations, such as vortex beams and
      vector beams. However, the nonlinear responses of SLM severely reduce the
      generation efficiency of these beams. In this paper, by calibrating the SLM to
      present a linear phase response in the scope of 0-2pi, we propose a convenient
      and efficient method of creating vector beams with arbitrary polarizations based
      on phase encoding. Compared with the common methods of generating vector beams,
      our approach can distinctly enhance the generation efficiency.

PMID- 29047642
TI  - Optical design and fabrication of palm/fingerprint uniform illumination system
      with a high-power near-infrared light-emitting diode.
AB  - In order to meet the requirements of uniform illumination for optical
      palm/fingerprint instruments and overcome the shortcomings of the poor uniform
      illumination on the working plane of the optical palm/fingerprint prism, a novel
      secondary optical lens with a free-form surface, compact structure, and high
      uniformity is presented in this paper. The design of the secondary optical lens
      is based on emission properties of the near-infrared light-emitting diode (LED)
      and basic principles of non-imaging optics, especially considering the impact of
      the thickness of the prism in the design. Through the numerical solution of
      Snell's law in geometric optics, we obtain the profile of the free-form surface
      of the lens. Using the optical software TracePro, we trace and simulate the
      illumination system. The results show that the uniformity is 89.8% on the working
      plane of the prism, and the test results show that the actual uniformity reaches
      85.7% in the experiment, which provides an effective way for realizing a highly
      uniform illumination system with high-power near-infrared LED.

PMID- 29047643
TI  - High-power, cladding-pumped all-fiber laser with selective transverse mode
      generation property.
AB  - We demonstrate, to the best of our knowledge, the first cladding-pumped all-fiber
      oscillator configuration with selective transverse mode generation based on a
      mode-selective fiber Bragg grating pair. Operating in the second-order (LP11)
      mode, maximum output power of 4.2 W is obtained with slope efficiency of about
      38%. This is the highest reported output power of single higher-order transverse
      mode generation in an all-fiber configuration. The intensity distribution profile
      and spectral evolution have also been investigated in this paper. Our work
      suggests the potential of realizing higher power with selective transverse mode
      operation based on a mode-selective fiber Bragg grating pair.

PMID- 29047644
TI  - Passively Q-switched Yb-doped all-fiber ring laser based on SBS feedback.
AB  - We report on a passively Q-switched Yb-doped all-fiber (YDF) ring laser based on
      stimulated Brillouin scattering (SBS) feedback in a 20-m single-mode fiber (SMF).
      The Q-switched pulses are generated from the Stokes pulses of SBS and amplified
      in the YDF. The 10-ns self-Q-switched pulses with ~1  kW maximum peak power are
      obtained. The repetition frequency of the pulse train is tuned from 4 to 12.6 kHz
      by changing the pump power in the experiment. A bandpass filter inserted in the
      laser cavity was used to suppress the time jitter of the Q-switched pulses.

PMID- 29047645
TI  - Flux density measurement of radial magnetic bearing with a rotating rotor based
      on fiber Bragg grating-giant magnetostrictive material sensors.
AB  - The rotational magnetic field of radial magnetic bearings characterizes
      remarkable time and spatial nonlinearity due to the eddy current and induced
      electromagnetic field. It is significant to experimentally obtain the features of
      the rotational magnetic field of the radial magnetic bearings to validate the
      theoretical analysis and reveal the discipline of a rotational magnetic field.
      This paper developed thin-slice fiber Bragg grating-giant magnetostrictive
      material (FBG-GMM) magnetic sensors to measure air-gap flux density of a radial
      magnetic bearing with a rotating rotor; a radial magnetic bearing test rig was
      constructed and the rotational magnetic field with different rotation speed was
      measured. Moreover, the finite element method (FEM) was used to simulate the
      rotational magnetic field; the measurement results and FEM results were
      investigated, and it was concluded that the FBG-GMM sensors were capable of
      measuring the radial magnetic bearing's air gap flux density with a rotating
      rotor, and the measurement results showed a certain degree of accuracy.

PMID- 29047646
TI  - Full-duplex radio-over-fiber system with tunable millimeter-wave signal
      generation and wavelength reuse for upstream signal.
AB  - A full-duplex radio-over-fiber system is proposed, which provides both the
      generation of a millimeter-wave (mm-wave) signal with tunable frequency
      multiplication factors (FMFs) and wavelength reuse for uplink data. A dual
      driving Mach-Zehnder modulator and a phase modulator are cascaded to form an
      optical frequency comb. An acousto-optic tunable filter based on a uniform fiber
      Bragg grating (FBG-AOTF) is employed to select three target optical sidebands.
      Two symmetrical sidebands are chosen to generate mm waves with tunable FMFs up to
      16, which can be adjusted by changing the frequency of the applied acoustic wave.
      The optical carrier is reused at the base station for uplink connection. FBG
      AOTFs driven by two acoustic wave signals are experimentally fabricated and
      further applied in the proposed scheme. Results of the research indicate that the
      2-Gbit/s data can be successfully transmitted over a 25-km single-mode fiber for
      bidirectional full-duplex channels with power penalty of less than 2.6 dB. The
      feasibility of the proposed scheme is verified by detailed simulations and
      partial experiments.

PMID- 29047647
TI  - Carrier-envelope phase stable, 5.4  MUJ, broadband, mid-infrared pulse generation
      from a 1-ps, Yb:YAG thin-disk laser.
AB  - We report on a simple scheme to generate broadband, MUJ pulses centered at 2.1
      MUm with an intrinsic carrier-envelope phase (CEP) stability from the output of a
      Yb:YAG regenerative amplifier delivering 1-ps pulses with randomly varying CEP.
      To the best of our knowledge, the reported system has the highest optical-to
      optical efficiency for converting 1-ps, 1 MUm pulses to CEP stable, broadband,
      2.1 MUm pulses. The generated coherent light carries an energy of 5.4 MUJ, at 5
      kHz repetition rate, that can be scaled to higher energy or power by using a
      suitable front end, if required. The system is ideally suited for seeding
      broadband parametric amplifiers and multichannel synthesizers pumped by
      picosecond Yb-doped amplifiers, obviating the need for active timing
      synchronization. Alternatively, this scheme can be combined with high-power
      oscillators with tens of MUJ energy to generate CEP stable, multioctave
      supercontinua, suitable for field-resolved and time-resolved spectroscopy.

PMID- 29047648
TI  - Interferometric synthetic aperture ladar using code division multiple access
      apertures.
AB  - This paper describes a multi-static interferometric synthetic aperture ladar
      (IFSAL) for high-resolution, high-precision 3D imaging. Code division multiple
      access apertures with periodic, pseudorandom noise waveforms are used to create
      aperture diversity and overcome the ambiguity associated with the aperture
      separation requirements for interferometric synthetic aperture ladar. The basic
      theory for mapping relative aperture phase to a high-precision elevation profile
      is derived for a multi-static IFSAL system and subsequent processing steps are
      presented. An analytic model and computer simulation are developed to demonstrate
      the 3D imaging capability of an IFSAL system.

PMID- 29047649
TI  - Influence of periodic texture profile and parameters for enhanced light
      absorption in amorphous silicon ultra-thin solar cells.
AB  - We have investigated the antireflection and light trapping properties of two
      dimensional grating arrays in the hexagonal symmetry with various texture
      morphologies. Optical simulation based on finite-difference time-domain (FDTD)
      analysis is carried out to understand the role of the structure profile for
      different periodicities and heights to achieve enhanced light trapping. The
      considered active medium of interest is 200-nm-thick hydrogenated amorphous
      silicon. Although the considered texture profiles possess an incremental change
      of refractive index from incident medium to active medium, a parabolic-shaped
      front side texture provides better antireflection effects owing to its high
      diffraction efficiencies in the higher-order modes as compared to other pattern
      morphologies. In the back side texture, the parabolic-shaped pattern also
      dominates with better light trapping efficiencies due to its ability to
      distribute a major amount of diffracted energy in the higher-order modes. The
      average reflection calculations in the wavelength range of 300-800 nm confirm
      that in both side textures, a periodicity of 500 nm with a height of 200 nm can
      be preferentially recommended for less reflection loss and improved scattering in
      oblique angles. The quantum efficiency calculation verifies that a device
      designed with these optimized parameters can offer improved efficiency for ultra
      thin solar cells.

PMID- 29047650
TI  - Low-cost, large-visual-field pyroelectric infrared linear device.
AB  - In this paper, a low-cost, large-visual-field pyroelectric infrared linear device
      fabricated using a multisensor was reported. The multisensor has been fabricated
      by connecting five unit sensors to a flexible circuit whose substrate is a
      polyethylene terephthalate film. The fabrication process of the pyroelectric
      sensor, microstructure, sensor electric properties, and device performances were
      studied. In order to obtain a larger visual field, the multisensor has been bent
      a specific angle. The visual field angle (more than 180 degrees ) of the device
      can be much larger than a traditional linear device (132 degrees ), and this
      greatly improved the detection capability of the pyroelectric infrared linear
      device with lower cost than the other methods.

PMID- 29047651
TI  - Diffuse back-illumination setup for high temporally resolved extinction imaging.
AB  - This work presents the development of an optical setup for quantitative, high
      temporal resolution line-of-sight extinction imaging in harsh optical
      environments. The application specifically targets measurements of automotive
      fuel sprays at high ambient temperature and pressure conditions where time scales
      are short and perceived attenuation by refractive index gradients along the
      optical path (i.e., beam steering) can be significant. The illumination and
      collection optics are optimized to abate beam steering, and the design criteria
      are supported by well-established theoretical relationships. The general effects
      of refractive steering are explained conceptually using simple ray tracing. Three
      isolated scenarios are analyzed to establish the lighting characteristics
      required to render the observed radiant flux unaffected by the steering effect.
      These criteria are used to optimize light throughput in the optical system,
      enabling minimal exposure times and high-temporal resolution capabilities. The
      setup uses a customized engineered diffuser to transmit a constant radiance
      within a limited angular range such that radiant intensity is maximized while
      fulfilling the lighting criteria for optimal beam-steering suppression. Methods
      for complete characterization of the optical system are detailed. Measurements of
      the liquid-vapor boundary and the soot volume fraction in an automotive spray are
      presented to demonstrate the resulting improved contrast and reduced uncertainty.
      The current optical setup reduces attenuation caused by refractive index
      gradients by an order of magnitude compared to previous high-temporal resolution
      setups.

PMID- 29047652
TI  - Characterization and modeling of Fabry-Perot ultrasound sensors with hard
      dielectric mirrors for photoacoustic imaging.
AB  - A Fabry-Perot ultrasound sensor with nonhygroscopic dielectric mirrors made out
      of Ta2O5 and SiO2 for use in photoacoustic tomography is described. The sensor
      offers flat frequency response up to 36 MHz, low noise-equivalent pressure (70
      Pa), and near-omnidirectional response up to 20 MHz as well as optical
      transparency for near-infrared illumination. A numerical model was developed to
      predict its frequency response, and the results were validated experimentally. An
      image of the human palm was acquired to demonstrate in vivo imaging capabilities.

PMID- 29047653
TI  - Time-domain measurements reveal spatial aberrations in a sub-surface two-photon
      microscope.
AB  - We show that in a nonlinear microscopy system the effects of chromatic and
      spherical aberrations are revealed by a difference in the focal positions
      corresponding to the shortest pulse duration and the minimum lateral resolution.
      By interpreting experimental results from a high-numerical-aperture two-photon
      microscope using a previously reported spatio-temporal model, we conclude that
      the two-photon autocorrelation of the pulses at the focal plane can be used to
      minimize both the chromatic and spherical aberrations of the system. Based on
      these results, a possible optimization strategy is proposed whereby the objective
      lens is first adjusted for minimum autocorrelation duration, and then the
      wavefront before the objective is modified to maximize the autocorrelation
      intensity.

PMID- 29047654
TI  - Surface damage induced by a combined millisecond and nanosecond laser.
AB  - The surface damage morphologies of single-crystal silicon induced by a combined
      pulse laser (CPL) and a single millisecond laser are investigated, respectively.
      The CPL includes a millisecond (ms) laser superposed by a nanosecond (ns) laser.
      Inspected by an optical microscope, it was found that the surface damage was more
      serious when the sample was irradiated by the CPL than by a single ms laser with
      the same incident laser energy. Besides surface cleavage, obvious ablation and
      fold areas were discovered by CPL irradiation. A two-dimensional spatial
      axisymmetric model was established to assess the difference between single ms
      laser and CPL irradiation and explain the generation mechanism of the different
      surface damage. This was attributed to the preheating effect by the ms laser and
      the surface damage caused by the ns laser.

PMID- 29047655
TI  - Formation of silver nanoparticles in Li2B4O7-Ag2O and Li2B4O7-Gd2O3-Ag2O borate
      glasses.
AB  - Results of investigations of 98.0Li2B4O7-2.0Ag2O and 97.0Li2B4O7-2.0Ag2O-1.0Gd2O3
      glasses with Ag nanoparticles (Ag NPs), formed by thermal treatment in vacuum and
      in air, are presented. Intensive plasmon absorption bands, connected with Ag NPs,
      were observed in their optical transmission spectra. It is ascertained that in
      volumes of both glasses there is formed a small number of Ag NPs, whereas their
      main mass is concentrated near the surface of samples. The mechanism of Ag NPs
      formation is proposed. A conclusion is drawn that annealing in vacuum does not
      necessarily require the presence of reducing ions, whereas formation of
      nanoparticles at annealing in air is impossible without reducing agents.
      Structural defects play a decisive role in the Ag NPs nucleation process. Radii
      of formed Ag NPs are estimated by the half-width of plasmon bands, and by means
      of small-angle x-ray scattering.

PMID- 29047656
TI  - Multiple spontaneously generated coherence and phase control of optical
      bistability and multistability in a tripod four-level atomic medium.
AB  - Optical bistability (OB) and optical multistability (OM) behaviors induced by
      multiple spontaneously generated coherence (SGC) are investigated theoretically
      in a tripod four-level atomic scheme. It is found that OB or OM is sensitive to
      the SGC effects, and the thresholds of OB can be controlled via changing the
      strength of multiple SGC or the relative phases of the applied fields. In
      addition, we can switch OB to OM by adjusting the twofold relative phases of the
      applied fields or vice versa.

PMID- 29047657
TI  - Sol-gel zirconia diffraction grating using a soft imprinting process.
AB  - A zirconia diffraction grating with high diffraction efficiency was fabricated
      using a soft imprinting technique and a sol-gel method. The imprinting process
      involved dropping zirconia nanoparticle dispersion onto a silicone
      (polydimethylsiloxane) mold, which was transferred from the patterned photoresist
      grating through the molding process. The first-order diffraction transmittance of
      the fabricated zirconia gel grating with a 1.0-MUm pitch and a depth of 0.58 MUm
      reached 29.4% at a wavelength of 632.8 nm (zeroth-order transmittance: 18.1%).
      This high aspect ratio grating can be fabricated in a simpler manner and at lower
      cost compared to conventional gratings.

PMID- 29047658
TI  - Absolute detector-based spectrally tunable radiant source using digital
      micromirror device and supercontinuum fiber laser.
AB  - High-accuracy absolute detector-based spectroradiometric calibration techniques
      traceable to cryogenic absolute radiometers have made progress rapidly in recent
      decades under the impetus of atmospheric quantitative spectral remote sensing. A
      high brightness spectrally tunable radiant source using a supercontinuum fiber
      laser and a digital micromirror device (DMD) has been developed to meet demands
      of spectroradiometric calibrations for ground-based, aeronautics-based, and
      aerospace-based remote sensing instruments and spectral simulations of natural
      scenes such as the sun and atmosphere. Using a supercontinuum fiber laser as a
      radiant source, the spectral radiance of the spectrally tunable radiant source is
      20 times higher than the spectrally tunable radiant source using conventional
      radiant sources such as tungsten halogen lamps, xenon lamps, or LED lamps, and
      the stability is better than +/-0.3%/h. Using a DMD, the spectrally tunable
      radiant source possesses two working modes. In narrow-band modes, it is
      calibrated by an absolute detector, and in broad-band modes, it can calibrate for
      remote sensing instrument. The uncertainty of the spectral radiance of the
      spectrally tunable radiant source is estimated at less than 1.87% at 350 nm to
      0.85% at 750 nm, and compared to only standard lamp-based calibration, a greater
      improvement is gained.

PMID- 29047659
TI  - Cassegrain antenna with a semitransparent secondary mirror.
AB  - With the help of the vector theory of reflection and refraction, a novel emitting
      Cassegrain antenna with a semitransparent secondary mirror has been proposed and
      analyzed for a distant point source. Based on the absorptivity valued at 3.00%
      and the reflectivity valued at 0.10%, this new emitting antenna can increase the
      transmission efficiency from 63.65% to 93.85%. In addition, an off-axis parabolic
      receiving antenna corresponding to the emitting antenna is designed and the 3D
      ray-trace simulation result is given. According to the simulation result, this
      receiving antenna can nicely converge the rays from the emitting antenna.

PMID- 29047660
TI  - Comparison of III-V/Si on-chip lasers with etched facet reflectors.
AB  - Electrically pumped heterogeneously integrated III-V/SiO2 semiconductor on-chip
      lasers with different types of etched facet reflectors are designed and
      fabricated and their lasing performances are characterized and compared. The III
      V quantum-well-based epitaxial layers are bonded on silica-on-silicon substrates
      and fabricated to form Fabry-Perot lasers with dry-etched rear facets. Three
      types of reflectors are demonstrated, which are etched facets terminated by air,
      benzocyclobutene, and metal with a thin layer of SiO2 insulator in-between. The
      laser devices are characterized and compared, including lasing threshold,
      external quantum efficiency, and output power, and show the impact of different
      types of etched facet reflectors on lasing performance.

PMID- 29047661
TI  - Highly concentrated, ring-shaped phase conversion laser-induced breakdown
      spectroscopy technology for liquid sample analysis.
AB  - A highly concentrated, ring-shaped phase conversion (RSPC) method was developed
      for liquid sample analysis using the laser-induced breakdown spectroscopy (LIBS)
      technique. In this work, test samples were prepared by mixing the metal particles
      with polyvinyl alcohol (PVA) supporter in liquid phase. With heat, the PVA
      solution solidified inside a modified glass petri dish, forming a metal-enriched
      polymer ring film. Distinguished from other traditional liquid-to-solid
      conversing methods, the proposed new method takes advantage of enhanced
      homogeneity for the target elements inside the ring film. The modified glass
      petri dish was used to control the ring-shaped concentration. Due to the
      specially designed circular groove at the bottom of this dish, where the PVA
      solution and liquid sample mixture accumulated, the target elements were
      concentrated in this small ring, which is beneficial for enhancing and
      stabilizing the plasma signals compared to the direct liquid sample analysis
      using LIBS. The limits of detection for Ag, Cu, Cr, and Ba obtained with the RSPC
      LIBS technology were 0.098  MUg.mL-1, 0.18  MUg.mL-1, 0.83  MUg.mL-1, and 0.046 
      MUg.mL-1, respectively, which provided greater improvement than the direct bulk
      liquid analysis using LIBS.

PMID- 29047662
TI  - Spherical aberration of an optical system and its influence on depth of focus.
AB  - This paper analyzes the influence of spherical aberration on the depth of focus
      of symmetrical optical systems for imaging of axial points. A calculation of a
      beam's caustics is discussed using ray equations in the image plane and
      considering longitudinal spherical aberration as well. Concurrently, the
      influence of aberration coefficients on extremes of such a curve is presented.
      Afterwards, conditions for aberration coefficients are derived if the Strehl
      definition should be the same in two symmetrically placed planes with respect to
      the paraxial image plane. Such conditions for optical systems with large
      aberrations are derived with the use of geometric-optical approximation where the
      gyration diameter of the beam in given planes of the optical system is evaluated.
      Therefore, one can calculate aberration coefficients in such a way that the
      optical system generates a beam of rays that has the gyration radius in a given
      interval smaller than the defined limit value. Moreover, one can calculate the
      maximal depth of focus of the optical system respecting the aforementioned
      conditions.

PMID- 29047663
TI  - Improvement of disturbing color effects depending on the axial color of an
      automotive headlamp lens.
AB  - Light-emitting diodes (LEDs) are causing big changes in the automotive lighting
      field. Optical systems with LEDs can use a plastic lens, which means almost all
      shapes can be made through plastic injection molding. Already, some car
      manufacturers are adopting this technology in their designs to express their own
      identities to customers. However, to use this technology, an important defect has
      to be overcome, which is color aberration near the cutoff line of the low-beam.
      In this paper, the criteria for measuring the color coordinates are established
      and simulations for axial color aberration in the plastic lens are carried out.

PMID- 29047664
TI  - Dynamic wavefront measurement with a pinhole linear polarizer point-diffraction
      interferometer.
AB  - We propose a pinhole linear polarizer point-diffraction interferometer (PLP-PDI)
      for dynamic wavefront measurements. The proposed interferometer uses a metallic
      wire grid linear polarizer that acts as a point-diffraction plate to generate an
      ideal spherical wave, from which we can obtain orthogonally polarized reference
      and test beams. The special polarization phase-shifting configuration allows four
      phase-shifted interferograms to be captured in a single shot with high precision
      and stability. The wavefront can then be reconstructed using a phase-unwrapping
      algorithm. In this paper, we describe the theory of the PLP-PDI and analyze the
      possible errors introduced by the device. The feasibility of the proposed PLP-PDI
      was verified by direct measurements of a wavefront. The experimental results show
      that the proposed PLP-PDI is an effective and efficient tool for the dynamic
      measurement of wavefronts.

PMID- 29047665
TI  - Design of a compact device to generate and test beams with orbital angular
      momentum in the EUV.
AB  - We present a compact design to generate and test optical-vortex beams with
      possible applications in the extreme ultraviolet (EUV) region of the
      electromagnetic spectrum. The device consists of a diffractive mask where both
      the beam with orbital angular momentum and the reference wavefront to test its
      phase are generated. In order to show that the proposal would work in the EUV,
      simulations and proof-of-principle experiments were performed, using typical
      parameters for EUV holography scaled to visible wavelengths. As the simplest
      case, we consider the well-known Laguerre-Gaussian (LG)-like beams, which have a
      single vortex in the propagation axis. To further test the versatility of the
      device, we consider Mathieu beams, more complex structured beams that may contain
      several vortices. In the experiment, a spatial light modulator was used to
      display the mask. As examples, we show the results for a LG-like beam with
      topological charge l=1 and Mathieu beams with topological charge l=2 and
      ellipticity q=2. These results show the potential of the device to generate a
      variety of beam shapes at EUV wavelengths.

PMID- 29047666
TI  - Angled-MMI-based wavelength splitters on silicon nitride waveguide platforms for
      fluorescence sensing.
AB  - Compact wavelength splitters based on angled multimode interferometers (AMMIs) on
      silicon nitride platforms working in visible lights are reported for fluorescence
      sensing applications. A diplexer and triplexer with different footprints are
      designed and experimentally demonstrated. The diplexer and triplexer have the
      insertion loss of ~1.7 and ~2.7  dB/channel with cross talks of less than -22  dB
      and -17  dB on target wavelengths, respectively. These splitters are used to
      distinguish the signals collected from two fluorescent dyes that give different
      emission spectra when excited with an excitation source, due to their different
      Stokes shifts. In the case of the triplexer, a third port is to collect the
      excitation light, both to monitor the remaining excitation power and to reduce
      the interference at the signal ports. A termination structure at the end of the
      AMMIs and input and output tapering waveguides as a part of the wavelength
      splitters are designed and their performances are presented.

PMID- 29047667
TI  - Tuneable and switchable liquid crystal laser protection system.
AB  - The use of a liquid crystal Lyot filter as a simple and compact switchable laser
      protection system is demonstrated. The system OFF state exhibits a wavelength
      independent transmission and switches to an ON state, which rejects a selected
      wavelength. The response time of the switchable system is <110  ms, depending on
      the rejected wavelength, with the ability for faster switching of <5  ms when
      using a lower-order rejection band. A rejection tuning range between 480 and 640
      nm is demonstrated, and the potential to operate outside of the visible spectrum
      is discussed. In the ON state, the transmission at the rejected wavelength was
      found to be effectively limited by the polarizer extinction ratio, while
      transmission at other wavelengths allows for partial observations through the
      system even when in protection mode.

PMID- 29047668
TI  - High spatial resolution zonal reconstruction with modified multishear method in
      frequency domain.
AB  - An exact multishear zonal algorithm is proposed to reconstruct two-dimensional
      wavefronts in frequency domain. The algorithm maintains the advantage of fast
      Fourier transform and loosens the "natural extension" requirement that the shear
      amounts must be divisors of sampling points N; therefore, it can be rapidly
      executed for large data arrays. The effect of tilt errors in multishear
      interferometry is analyzed and compensated in our method. The presented algorithm
      is applicable for a general aperture shape by using an iterative method.
      Application of large shears is allowed, and high resolution of the reconstructed
      wavefront can be achieved. Results of numerical simulations demonstrate the
      capability of our method.

PMID- 29047669
TI  - Ultraviolet optical vortex generation using a pair of beta-BaB2O4 crystals with
      inverted orientations.
AB  - Picosecond pulsed frequency-doubled optical vortices were generated using a pair
      of beta-BaB2O4 crystals with their c axes inverted. This arrangement produced
      high-quality ultraviolet vortex output with low spatial separation of the phase
      singularity at a conversion efficiency of ~40%. We also discuss the theoretical
      spatial form and beam propagation of the ultraviolet vortex output.

PMID- 29047670
TI  - Polarization smoothing for single beam by a nematic liquid crystal scrambler.
AB  - Polarization smoothing (PS) is a key approach to suppress laser plasma
      instabilities (LPI) in inertial confinement fusion (ICF) experiments. Here, we
      propose a liquid crystal (LC) PS element to realize single beam smoothing and
      demonstrate its smoothing effect, in principle, with a 2*2 LC polarization
      checkerboard, which reduces the laser intensity variation in the focal spot to
      78.4%. LC PS elements, which have potential applications in high-power ICF laser
      drivers, have many advantages because they are easy to fabricate, cost effective,
      flexible, and large.

PMID- 29047671
TI  - Measurement of pile-up around spherical indentation by image-plane digital
      holography.
AB  - Instrumented indentation has been used to measure mechanical properties, residual
      stresses, hardness, and viscoelastic properties, among others, due to its fast
      and nondestructive procedure. The accurate determination of the contact area
      between the indenter and the material is important for material property
      measurements and usually is masked by the pile-up or sink-in phenomenon. This
      paper presents the application of dual-wavelength image-plane digital holography
      in order to achieve a full-field determination of the topography around the
      indentation mark. The optical configuration was able to identify pile-up with
      magnitudes close to 25 MUm. Measurement results were compared with the references
      performed by a commercial focus-variation device showing positive agreement
      between the obtained profiles. Additionally, most of the points presented
      differences between measurements lower than 3 MUm.

PMID- 29047672
TI  - Submicrometer-sized nonspherical particle separation by laser beam.
AB  - The radiation pressure exerted on sub-micrometer-size particles is shown to be an
      important factor predetermining the impact coordinates of the particles after
      being illuminated by a laser beam. Unlike spherical particles, the nonspherical
      ones can be deflected perpendicularly to the beam direction if the momentum
      transfer from the laser beam to a particle is large enough. Such an optical
      sorting is a useful technology, which can be used to isolate spherules of a
      specific size from a population of particles of random sizes and shapes. The
      system of ideal spheres has a wide range of applications in industry and also in
      the development of targeted optical devices, and so the methods for fast contact
      less particle separation are expected to lead to considerable progress in the
      field. The theoretical model we have developed is demonstrated in a set of
      numerical experiments on metallic and nonmetallic particles.

PMID- 29047673
TI  - Effects of a nonideal half-wave plate on the gain ratio calibration measurements
      in polarization lidars.
AB  - A half-wave plate (HWP) is a critical component for calibrating the gain ratio in
      polarization lidars. In this paper, the effects of a nonideal HWP on the gain
      ratio calibration measurements are analyzed. We focus on the +/-45 degrees 
      method and the multi-rotation HWP method, which are the two main approaches for
      calibrating the gain ratio. Specifically, we discuss the influences of a nonideal
      HWP from two scenarios: an HWP with nonideal polarization properties and an ideal
      HWP under nonideal external conditions. The allowable ranges of relevant
      parameters for the nonideal polarization properties of HWPs are obtained, which
      can help to determine qualified HWPs in polarization lidars. Several external
      conditions, including ambient temperature variations, wavelength differences, and
      the tilt angles of HWPs, are also analyzed in detail. To the best of our
      knowledge, this paper represents the first comprehensive study on the effects of
      nonideal HWPs on the gain ratio calibration measurements, offering some
      guidelines on choosing a qualified HWP for proper use in polarization lidars.

PMID- 29047674
TI  - Droplet sizing and mixture fraction measurement in liquid-liquid flows with
      rainbow-angle diffractometry.
AB  - The capabilities and resolution of the rainbow technique were extended to
      estimate the size distribution and composition of droplets in liquid-liquid
      systems. For these droplets, essentially characterized by a low relative
      refractive index (m~1.001-1.20), the first-order rainbow is localized in the near
      forward to sideways region. It exhibits an unusually higher contrast in the
      parallel polarization due to the vicinity of the rainbow and the Brewster angles.
      A numerical study revealed that a few thousand to ten thousand droplets were
      necessary to obtain reliable estimations of the first moments of typical droplet
      size distributions when the diffractometer is operated as an ensemble averaging
      technique. The importance of the accuracy of the light scattering model and the
      inverse methods used are also documented. Experimental results performed on free
      rising submillimeter to millimeter droplets of various compositions showed that a
      global resolution of 1% to 5% of their mean diameter and about 1.6*10-4 of the
      dispersion on their refractive index (i.e., 3% in the mixture fraction of oily
      droplets in water) could be achieved, which enhances the perspectives on mixing
      and extraction studies in liquid-liquid systems.

PMID- 29047675
TI  - Heterodyne high-spectral-resolution lidar.
AB  - In this work, a novel lidar technique to perform high-spectral-resolution
      measurements of the atmospheric backscatter is discussed and the first results
      are presented. The proposed method, which relies on a heterodyne detection
      receiver, allows us not only to separate the molecular and the aerosol component
      of the atmospheric backscatter, but also to investigate the spectral shape of the
      Rayleigh-Brillouin line. As in the case of the direct-detection high-spectral
      resolution lidars, the separation of the different scattering processes would
      allow an independent system calibration and aerosol extinction measurements. The
      proposed retrieval technique was successfully tested on the Deutsches Zentrum fur
      Luft- und Raumfahrt airborne Doppler wind lidar system with measurements
      conducted during different measurement campaigns and under different atmospheric
      conditions. In light of these results, further ideas for the implementation of a
      dedicated heterodyne high-spectral-resolution lidar are discussed.

PMID- 29047676
TI  - Wavelength and ambient luminance dependence of laser eye dazzle.
AB  - A series of experiments has been conducted to quantify the effects of laser
      wavelength and ambient luminance on the severity of laser eye dazzle experienced
      by human subjects. Eight laser wavelengths in the visible spectrum were used (458
      647 nm) across a wide range of ambient luminance conditions (0.1-10,000  cd.m-2).
      Subjects were exposed to laser irradiance levels up to 600  MUW.cm-2 and were
      asked to recognize the orientation of optotypes at varying eccentricities up to
      31.6 deg of visual angle from the laser axis. More than 40,000 data points were
      collected from 14 subjects (ages 23-64), and these were consolidated into a
      series of obscuration angles for comparison to a theoretical model of laser eye
      dazzle. Scaling functions were derived to allow the model to predict the effects
      of laser dazzle on vision more accurately by including the effects of ambient
      luminance and laser wavelength. The updated model provides an improved match to
      observed laser eye dazzle effects across the full range of conditions assessed.
      The resulting model will find use in a variety of laser safety applications,
      including the estimation of maximum dazzle exposure and nominal ocular dazzle
      distance values.

PMID- 29047677
TI  - Simultaneous analysis of Cr and Pb in contaminated pork by laser-induced
      breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) as a rapid and green method was used
      to detect heavy metals Cr and Pb in pork contaminated in the lab. The laser
      induced plasma was generated by a Q-switched Nd:YAG laser, and the LIBS signal
      was collected by a spectrometer with a charge-coupled device detector. The
      traditional calibration curves (CC) and multivariate partial least squares (PLS)
      algorithm were applied and compared to validate the accuracy in predicting the
      content of heavy metals in samples. The results demonstrated that the correlation
      coefficient of CC is poor by the classical univariate calibration method, so the
      univariate calibration analysis cannot effectively serve the quantitative purpose
      in analyzing heavy metals' residue in pork with a complex matrix. The analysis
      accuracy was improved effectively by the PLS method, and the correlation
      coefficient is 0.9894 for Cr and 0.9908 for Pb. The concentration of Cr and Pb in
      samples from a prediction set was obtained using the PLS calibration method, and
      the average relative errors for the 21 samples in the prediction set are lower
      than 6.53% and 7.82% for Cr and Pb, respectively. The investigated results
      display that the matrix effect would be reduced effectively during the
      quantitative analysis of pork by a LIBS-combined PLS model, and the predictive
      accuracy would be improved greatly compared to traditional univariate analysis.

PMID- 29047678
TI  - Angular-dependent light scattering from cancer cells in different phases of the
      cell cycle.
AB  - Cancer cells in different phases of the cell cycle result in significant
      differences in light scattering properties. In order to harvest cancer cells in
      particular phases of the cell cycle, we cultured cancer cells through the process
      of synchronization. Flow cytometric analysis was applied to check the results of
      cell synchronization and prepare for light scattering measurements. Angular
      dependent light scattering measurements of cancer cells arrested in the G1, S,
      and G2 phases have been performed. Based on integral calculations for scattering
      intensities from 5 degrees  to 10 degrees  and from 110 degrees  to 150 degrees ,
      conclusions have been reached. Clearly, the sizes of the cancer cells in
      different phases of the cell cycle dominated the forward scatter. Accompanying
      the increase of cell size with the progression of the cell cycle, the forward
      scattering intensity also increased. Meanwhile, the DNA content of cancer cells
      in every phase of the cell cycle is responsible for light scattering at large
      scatter angles. The higher the DNA content of cancer cells was, the greater the
      positive effect on the high-scattering intensity. As expected, understanding the
      relationships between the light scattering from cancer cells and cell cycles will
      aid in the development of cancer diagnoses. Also, it may assist in the guidance
      of antineoplastic drugs clinically.

PMID- 29047679
TI  - Low driving voltage ITO doped polymer-dispersed liquid crystal film and reverse
      voltage pulse driving method.
AB  - This paper investigates the effects of indium tin oxide (ITO) powders on the
      driving voltage of polymer-dispersed liquid crystal (PDLC). The threshold voltage
      (Vth) and driving voltage (Vd) can be reduced through doping the ITO powders; in
      particular, the Vd is 5.8 V when the weight ratio of ITO is 1.5 wt. %. The
      relationship between the applied voltage and off-time of PDLC has been
      investigated; the lower the applied voltage, the shorter the off-time. On this
      basis, the reverse voltage pulse driving method was proposed; this driving method
      uses the driving signal to reduce the off-time of PDLC.

PMID- 29047680
TI  - Broadband 2 * 2 lithium niobate electro-optic switch based on a Mach-Zehnder
      interferometer with counter-tapered directional couplers.
AB  - We demonstrate a broadband 2*2 electro-optic switch based on a Mach-Zehnder
      interferometer with counter-tapered directional couplers (DCs). The counter
      tapered DC is introduced here to replace the conventional one formed with uniform
      waveguides so that a splitting ratio of 50%?50% is much easier to be realized
      over a wide wavelength range and, hence, increase bandwidth of the switch. The
      proposed switch is fabricated with x-cut lithium niobate by the annealed proton
      exchange process. A comparison of several experimental devices, fabricated on the
      same chip with the conventional and different counter-tapered DCs, respectively,
      confirms the increase of the bandwidth and the improvement of the fabrication
      tolerance by using the counter-tapered DC. Our fabricated best device, which has
      a length of ~22  mm, exhibits an ~85  nm bandwidth for an extinction ratio (ER)
      higher than 15 dB and a maximum ER of ~35  dB at 1563 nm at a driving voltage of
      6.0 V. The insertion losses are less than 8.5 dB for all channels. Our proposed
      optical switch could find applications in wavelength-division-multiplexing
      optical communication systems.

PMID- 29047681
TI  - Analysis of beam propagation characteristics in gain-guided, index antiguided
      fibers with the beam propagation method.
AB  - The transmission properties of beams in gain fibers are studied with the complex
      refractive index beam propagation method (CRI-BPM). The method is checked by
      comparison with an analytic method. The behavior of a gain-guided, index
      antiguided (GG-IAG) fiber with different gain coefficients is studied. The
      simulation results show that the signal can transfer in the fiber with almost no
      loss when the gain coefficient reaches the threshold of the fundamental mode, and
      the shape of output spot will have no major changes when the gain coefficient is
      over the thresholds of high-order modes, even when the mode competition is not
      obvious. The CRI-BPM can predict the changes in light power and light mode at the
      same time, and will be very useful in the designing of fiber amplifiers and
      lasers with complex structures. More factors will be considered in this method to
      provide reference for practical application in our further research.

PMID- 29047682
TI  - Surface recovery algorithm in white light interferometry based on combined white
      light phase shifting and fast Fourier transform algorithms.
AB  - Quality control of micro-nano structured and freeform surfaces is becoming
      increasingly important, which leads to challenging requirements in the
      measurement and characterization of rough and highly reflective surfaces. As an
      important measurement technique, white light scanning interferometry (WLSI) is a
      fast noncontact method to measure three-dimensional (3D) surface profiles.
      Nevertheless, the existing WLSI 3D surface reconstruction algorithms are prone to
      environmental vibrations and phase changes caused by reflections on the tested
      surface. A novel peak detecting algorithm that combines the white light phase
      shifting interferometry (WLPSI) method and fast Fourier transform (FFT) coherence
      peak-sensing technique is proposed in this paper, which can accurately determine
      the local fringe peak and improve the vertical resolution of the measurement. A
      microcomponent (10 MUm standard step height) and a spherical surface were used as
      test specimens to evaluate the proposed method. Both simulated and experimental
      results show that the proposed algorithm improves the precision and anti
      interference ability of the WLPSI and FFT methods, which can effectively reduce
      the batwing effects at the edges and solve the problem of positioning error in
      the maximum modulation.

PMID- 29047683
TI  - Toward a unified model for predicting color quality of light sources.
AB  - Considering that the existing color quality (CQ) metrics for light sources cannot
      correlate well with the subjective evaluation, in an immersive environment
      equipped with a multichannel LED light source, a psychophysical experiment by
      categorical judgment method was carried out to assess the three perception
      related CQ attributes of light sources in terms of naturalness, colorfulness, and
      preference. The experiment collected the subjective responses to these attributes
      of up to 41 metameric spectra at each of four test correlated color temperatures
      (CCTs) ranging from 2800 to 6500 K, which covers the usual white-light range for
      general lighting. The results indicate that preference exhibits relatively high
      correlation with naturalness and colorfulness, and naturalness is weakly related
      to colorfulness. Besides, 20 typical CQ metrics were adopted to examine their
      validity in characterizing the subjective data, confirming their limited
      performance. Meanwhile, the underlying relationship of these metrics and the
      subjective data was also analyzed by the multidimensional scaling, revealing that
      almost all metrics can correspond to one attribute of naturalness, colorfulness,
      and preference, and that the saturation level is identified as a critical factor
      affecting these attributes. Based on these results, a unified CQ model was
      developed with a multiple nonlinear regression equation combining the
      Illuminating Engineering Society of North America color rendition method. The
      model accords satisfactorily with the subjective evaluation, while being
      applicable to a wide range of CCTs.

PMID- 29047684
TI  - Development of a compact underwater laser-induced breakdown spectroscopy (LIBS)
      system and preliminary results in sea trials.
AB  - The exploitation and research of deep-sea hydrothermal vent has been an issue of
      great interest in ocean research in recent years. Laser-induced breakdown
      spectroscopy (LIBS) has great potential for ocean application due to the
      capabilities of stand-off, multiphase, and multielement analysis. In this work, a
      newly developed compact 4000 m rated LIBS system (LIBSea) is introduced with
      preliminary results of sea trials. The underwater system consists of an Nd:YAG
      single-pulsed laser operating at 1064 nm, an optical fiber spectrometer, an
      optics module, and an electronic controller module. The whole system is housed in
      an L800  mm*phi258  mm pressure housing with an optical window on the end cap. It
      was deployed on the remote operated vehicle Faxian on the research vessel Kexue,
      and in June 2015 was successfully applied for hydrothermal field measurements at
      the Manus area. The obtained results are shown that the LIBS system is capable of
      detecting elements Li, Na, K, Ca, and Mg in the hydrothermal area. Profiles of
      LIBS signals of elements K and Ca have also been obtained during the sea trial.
      The results show that the K emission line is gradually broadened with depth from
      sea surface to sea floor (1800 m or so); the K intensity shows a hump shape with
      maximum value at about 1050 m. The Ca emission line is rapidly broadened below
      400 m and slowly narrowed to the sea floor; the Ca intensity shows no obvious
      change below 400 m and increases continuously to sea floor. A very interesting
      finding is that the small fluctuations of intensity profile curve of Ca show a
      degree of correlation with seawater temperature change. The sea trial results
      prove the performance of LIBSea. After further optimization, it is hoped to apply
      the LIBS system to the in situ mineral deposits and hydrothermal vent fluid
      detection in deep sea.

PMID- 29047685
TI  - Nondestructive determination of optical properties of a pear using spatial
      frequency domain imaging combined with phase-measuring profilometry.
AB  - Spatial frequency domain imaging (SFDI), as a rapid, noncontact, and scan-free
      method, can realize wide-field, quantitative optical property mapping and
      tomographic imaging for a biological sample. Phase-measuring profilometry (PMP)
      is a surface profile characterization method. Since the projection of structured
      light onto an object is the basis for PMP and SFDI, the SFDI system is capable of
      performing both techniques. In this work, we present the results of a feasibility
      study with the developed SFDI system to realize acquisition of the optical
      property information and the surface profile information. The surface profile
      information was used to correct the absorption (MUa) maps and reduced scattering
      (MUs') maps. The evaluation of correction effect of the PMP and the calibration
      and calculation of detection accuracy of the SFDI system were realized by using a
      series of self-made hemispheric and homogeneous solid phantoms covering a wide
      range of absorption and reduced scattering coefficients. The results show that
      the MUa and MUs' maps become more uniform after using profilometry correction.
      The maximum relative errors of the system after profilometry correction and
      calibration were 8.74% for MUa and 4.97% for MUs' at the wavelength of 527 nm,
      respectively. A case study was carried out on a pear to verify the application
      prospect of the method in the field of agricultural products quality inspection.
      Results indicate that MUa and MUs' maps of a pear after profilometry correction
      and calibration were more uniform and more comparable with the reported values.

PMID- 29047686
TI  - Improved cumulative probabilities and range accuracy of a pulsed Geiger-mode
      avalanche photodiode laser ranging system with turbulence effects.
AB  - There exists a performance limitation in a pulsed Geiger-mode avalanche
      photodiode laser ranging system because of the echo intensity random fluctuation
      caused by turbulence effects. To suppress the influence of turbulence effects, we
      present a cumulative pulse detection technique with the ability to achieve
      improved cumulative probabilities and range accuracy. Based on the modulated
      Poisson model, the cumulative probabilities, range accuracy, and their
      influencing factors are investigated for a cumulative Q-switched laser pulse
      train. The results show that the improved cumulative probabilities and range
      accuracy can be obtained by utilizing cumulative pulse detection, with the
      condition that the echo intensity is 10, the echo pulse width is 10 ns, and the
      turbulence degree is 3, the target detection probability increases by 0.4, the
      false alarm probability decreases by 0.08, and the accuracy and precision
      increase by 46 cm and 27 cm, respectively.

PMID- 29047687
TI  - Ultraviolet polarizer with a Ge subwavelength grating.
AB  - A polarizer with high extinction ratio (ER) was developed in the ultraviolet
      wavelength region using a germanium subwavelength grating (Ge-SWG). By utilizing
      an eigenmode with the Ge-SWG, a high ER was numerically predicted to exist
      without requiring a high structural aspect ratio. After using lithography to
      fabricate the proposed Ge-SWG, an experimentally high ER value of 17.4 dB was
      reached at a wavelength of 360 nm in the developed Ge-SWG, which had a very low
      structural aspect ratio of 1.67.

PMID- 29047688
TI  - Optimized design method for the inner surface of a conformal dome based on the
      ray tracing approach.
AB  - Traditional optical domes are spherical, which introduces constant aberrations
      with look angle. However, spherical domes are not optimum for reducing
      aerodynamic drag. Conformal domes deviate from spherical to reduce drag but they
      generate dynamic aberrations varying significantly with look angle in the field
      of regard. Thus, conformal domes require unique challenges for aberration
      correction. This paper presents a method to reduce the dynamic aberrations
      through designing the inner surface of conformal domes. This method follows the
      principle that the optical axis ray of the imaging system maintains the same
      direction after refraction through the conformal dome for different look angles.
      Based on this principle, equations that the inner surface should satisfy are
      established and a numerical solution method is introduced. Eventually, Zernike
      polynomial coefficients of Z4, Z5, Z8, and Z9, which represent defocus,
      astigmatism, coma, and spherical aberration, respectively, are analyzed for
      quadratic domes with different inner surfaces. Compared with domes with
      traditional inner surfaces, quadratic domes with the inner surfaces calculated by
      this method have smaller Zernike aberrations. In conclusion, this design method
      for the inner surface can effectively reduce dynamic aberrations.

PMID- 29047689
TI  - Dependence of plasmon coupling on curved interfaces.
AB  - The optical properties of coupled plasmon systems can be tuned by individual
      material and geometry, gap distance, and surrounding dielectric. This paper
      reports a dramatic effect of a curved interface in the nanoparticles dimer on the
      optical responses. Compared with gold nanorod (AuNR) monomer, AuNR dimers with
      different assembly types (such as end-to-end and side-by-side) can manipulate the
      longitudinal surface plasmon resonance (SPRL) to red/blueshift. The
      electromagnetic field of the dimer is further enhanced in the interactive region.
      Under the incident polarization along the gap, a new resonance mode will be
      excited when AuNR dimers touch each other, and the SPR mode turns to blueshift
      from redshift due to the formation of the conductive coupling. It can be assumed
      that when one of the interactive surfaces is curved, an additional plasmon
      resonance can be stimulated under the polarization of incident light along the
      gap. The particular phenomenon can be explained by the plasmon hybridization
      theory. Silver nanocubes dimers (with sharp or smooth corners and edges) also
      possess the same property. Supported by finite-difference time-domain solutions,
      the coupled plasmon resonance mode represents high sensitivity to structural
      geometry.

PMID- 29047690
TI  - Frequency-dependent noise figure analysis of continuous photonic time-stretch
      system.
AB  - In this paper, the frequency-dependent noise figure of a continuous photonic time
      stretch system is theoretically analyzed and experimentally demonstrated.
      Mathematic analysis discloses that the frequency-dependent noise figure in the
      continuous photonic time-stretch system is mainly owing to the dispersion-induced
      phase shift in the link. In the experiment, a completely continuous signal is
      reconstructed with time-interleaved joining of four sections of time-stretched
      signals from optical wavelength-division de-multiplexing channels. The result of
      the frequency-dependent noise figure property agrees well with that of
      theoretical analysis.

PMID- 29047691
TI  - Nanoantenna arrays combining enhancement and beam control for fluorescence-based
      sensing applications.
AB  - This paper presents measured fluorescence enhancement results for ~250*250
      element aluminum nanoantenna arrays fabricated using electron beam lithography.
      The arrays have been designed to use diffractive coupling to enhance and control
      the direction of fluorescent emission. Highly directional emission is obtained at
      the designed angles with beam widths simulated to be in the range of 4-6 degrees
      . Angle-resolved spectroscopy measurements of dye-coated nanoantenna arrays were
      in good agreement with finite difference time domain modeling. Critically, these
      results were obtained for near UV wavelengths (~360  nm), which is relevant to a
      number of biosensing applications.

PMID- 29047692
TI  - Glucose sensing in oral mucosa simulating phantom using differential absorption
      based frequency domain low-coherence interferometry.
AB  - The superluminescent diode based differential absorption frequency domain low
      coherence interferometry (FD-DALCI) technique is proposed and demonstrated for
      sensing physiological concentrations of glucose (0-250 mg/dl) in oral mucosa
      simulating phantoms (intralipid of concentrations 0.25-0.50%) with wavelengths at
      1589 and 1310 nm. The proposed technique allows simultaneous measurements of
      refractive index based spectral shift and estimation of physiological
      concentration of glucose in intralipid with scattering characteristics using the
      differential absorption approach. The sensitivity of the glucose concentration
      obtained by spectral shift measurement was ~0.016  nm/(mg/dl), irrespective of
      the intralipid concentration. The resolution of the glucose level was estimated
      to be ~15  mg/dl in 0.25% intralipid and ~19  mg/dl in 0.5% intralipid using the
      FD-DALCI technique.

PMID- 29047693
TI  - Fiber-based tools: material removal and mid-spatial frequency error reduction.
AB  - This paper details the feasibility of using fiber-based tools in a computer
      numerical control (CNC) environment to process optical materials and their
      ability to reduce the amplitude of pre-existing mid-spatial-frequency (MSF)
      surface errors. The work is motivated by earlier research conducted by the group
      exploring the ability of polymeric fiber-based tools to remove material from BK7
      glass substrates. To evaluate these tools in a CNC environment, three tasks are
      explored. First, the ability of the tools to maintain their form and material
      removal profile while operating under translational conditions is explored.
      Second, the ability of the tools to disengage and re-engage with the workpiece
      edge, and how this affects the tool's material removal profile. Finite element
      (FE) modelling of the fiber-workpiece edge interaction was conducted to support
      the experimental work. And third, the deterministic behavior of the tool under
      full raster conditions is verified. Testing on a 3-axis CNC machine tool
      demonstrated that the tooling is sufficiently robust and stable to operate under
      translational and rotational speeds of 30 mm/s and 1000 rpm, respectively. Both
      the FE modeling and experimental testing confirmed the truncation of a fiber's
      material removal profile as a fiber extends beyond the workpiece edge. The
      ability of fiber-based tools to reduce MSF errors was explored both through FE
      modeling and experimental testing on germanium samples. Both the FE model and
      experimental results demonstrate that fiber-based tools can successfully reduce
      pre-existing MSF errors.

PMID- 29047694
TI  - Independence between intensity and phase noise of superluminescent diodes in the
      low-frequency domain.
AB  - We theoretically and experimentally demonstrate a method for measuring the phase
      and intensity noise and their correlation in superluminescent diodes. A Michelson
      interferometer containing strongly unbalanced paths has been developed to measure
      the noise. By the spectral analysis of the photocurrents in detectors, the
      intensity noise is about twice the value of the phase noise in the
      superluminescent diode. The more interesting result we obtained is the
      experimental evidence that the intensity noise and the phase noise are mutually
      independent. The correlation coefficient of the intensity noise and the phase
      noise fluctuates between -0.08 and 0, which shows scarcely any sign of amplitude
      phase noise correlation. The results offer a basic premise for the analysis of
      broadband light sources.

PMID- 29047695
TI  - Wide-field fluorescence tomography with composited epi-illumination of multi
      frequency sinusoidal patterns.
AB  - We present a spatial-frequency domain (SFD) fluorescence tomography (FT) for
      acquiring three-dimensional fluorophore distribution in turbid media. The
      approach uses a composited epi-illumination of multi-frequency sinusoidal
      patterns on a sample of semi-infinite geometry and demodulates the measured data
      with a generalized phase shifting scheme to calculate the modulation transfer
      function (MTF) at each frequency. This method results in a significantly reduced
      number of the optical field measurements, as compared to those with separate
      illumination of single-frequency sinusoidal patterns, and, thereby, achieves a
      fast data acquisition that is desired for a dynamic imaging application.
      Fluorescence yield images are recovered with the normalized Born formulated
      inversion of the diffusion model by simultaneously using the multi-frequency
      MTFs. Simulative and experimental reconstructions are performed in comparison
      with the single-frequency scheme to validate the proposed algorithm. The results
      suggest that adoption of the multi-frequency strategy to the SFD-FT can
      substantially improve the reconstruction quality, as well as its imaging
      resolution and quantitative accuracy.

PMID- 29047696
TI  - Full-reference quality assessment of stereoscopic images by learning binocular
      visual properties.
AB  - Stereoscopic imaging technology has been growingly prevalent driven by both the
      entertainment industry and scientific applications in today's world. But
      objective quality assessment of stereoscopic images is a challenging task. In
      this paper, we propose a novel stereoscopic image quality assessment (SIQA)
      method by jointly considering monocular perception and binocular interaction. As
      the most significant contribution of this study, binocular perceptual properties
      of simple and complex cells are considered for full-reference (FR) SIQA.
      Specifically, the proposed scheme first simulates the receptive fields of simple
      cells (one class of V1 neurons) using a push-pull combination of receptive fields
      response, which is used to represent a monocular cue. Further, the receptive
      fields of complex cells (the other class of V1 neurons) are simulated by using
      binocular energy response and binocular rivalry response, which are used to
      represent a binocular cue. Subsequently, various quality-aware features are
      extracted from the response of area V1 by calculating the self-weighted histogram
      of the local binary pattern on four types of feature maps of similarity
      measurement that will change in the presence of distortions. Finally, kernel
      ridge regression is used to simulate a nonlinear relationship between the quality
      aware features and objective quality scores. The performance of our method is
      evaluated over popular stereoscopic image databases and shown to be competitive
      with the state-of-the-art FR SIQA algorithms.

PMID- 29047697
TI  - Dual-grating dielectric accelerators driven by a pulse-front-tilted laser.
AB  - This paper investigates numerically dual-grating dielectric laser-driven
      accelerators driven by a pulse-front-tilted (PFT) laser, which extends the
      interaction length and boosts the electrons' energy gain. The optical system
      necessary to generate PFT laser beams with an ultrashort pulse duration of 100 fs
      is also studied in detail. Through two-dimensional particle-in-cell simulations,
      we show that such a PFT laser effectively increases the energy gain by (91+/-25)
      % compared to that of a normally incident laser with a waist radius of 50 MUm for
      a 100-period dual-grating structure.

PMID- 29047698
TI  - One-pump fiber optical parametric amplifier in presence of dispersion
      fluctuations: impact of fourth-order dispersion coefficient.
AB  - The impact of random dispersion fluctuations on the gain and saturation behavior
      of a one-pump fiber optical parametric amplifier (1-P FOPA) in the presence of
      fourth-order dispersion coefficient (beta4) is investigated. Three coupled
      amplitude equations with fiber losses are solved numerically for the calculation
      of the pump, signal, and idler. The performances of 1-P FOPA are also analyzed
      with variation of dispersion fluctuation amplitude (sigma) and correlation length
      (Lc). Based on the numerical results, it is found that the gain spectra and
      saturation curves exhibit some differences when beta4 is considered. In
      comparison with the case where beta4 is ignored, the peak gain remains the same,
      but the 3 dB bandwidth increases when beta4 exists. Another notable difference is
      that the saturation power is shifted to lower or higher values, depending on the
      sigma and Lc parameters. In general, the peak gain reduces as sigma increases,
      and the peak gain reduction is greater for the case of shorter Lc. The numerical
      analysis is probably useful, especially for the case where the signal wavelength
      is detuned far from the pump wavelength.

PMID- 29047699
TI  - Deconvolution of spectral power distribution of high-power laser diode arrays.
AB  - A novel method is proposed to predict the spectral power distributions (SPDs) of
      individual emitters in a high-power laser diode (LD) array. The proposed method
      deconvolutes the SPD of an LD array by taking into account the thermal cross-talk
      effect as well as the current competition effect. A complete analytical
      expression to deconvolute the SPD of an LD array is described. The expression
      contains four key parameters that are to be measured experimentally: (1) the
      normalized SPD of the central emitter, (2) the temperature coefficient of
      wavelength, (3) the current competition constant, and (4) the maximum power of
      the center emitter. The method is implemented with a commercial water-cooled high
      power LD array. The SPD of the LD array predicted from the SPDs of individual
      emitters are compared with the experimentally measured SPD of the LD array. The
      results show excellent agreement in both shape and magnitude, which corroborates
      the validity of the proposed method.

PMID- 29047700
TI  - Reflectionless compact nonmagnetic optical waveguide coupler design based on
      transformation optics.
AB  - The design of an optical waveguide coupler has several challenges, such as
      reflection losses at the interfaces of the coupler, material complexity for
      optical applications, and the coupling between arbitrary materials at the input
      and the output of the coupler. In this paper, for the first time to the best of
      our knowledge, we propose a solution to overcome the above difficulties. For this
      purpose, we introduce an auxiliary transformation function and an impedance
      scaling function. The auxiliary function specifies the matched dielectric
      materials at the input and output interfaces of the coupler, and the scaling
      function suppresses the reflections and makes the material nonmagnetic for
      transverse magnetic (TM) polarization. As a result, an optical waveguide coupler
      is designed that can ideally couple two waveguides with arbitrary dielectric
      materials and arbitrary cross sections using a nonmagnetic material. Validation
      of the design method is done by using COMSOL Multiphysics.

PMID- 29047701
TI  - Numerical investigation of nonlinear shrinkage effects in volume holographic
      gratings.
AB  - Photopolymers are widely used as a recording medium in holographic data storage,
      but they shrink during polymerization. We proposed a nonlinear shrinkage model to
      numerically evaluate the effect of photopolymer shrinkage on signal quality.
      Specifically, we developed both a numerical model in which the shrinkage factor
      is determined locally according to the light intensity, and a numerical
      simulation method that can handle computational lattices distorted by shrinkage.
      We clarified the influence of shrinkage on diffraction efficiency, angle
      selectivity, wavelength selectivity, signal-to-noise ratio, and symbol error
      rate. This study provides useful information for system design of holographic
      data storage.

PMID- 29047702
TI  - Symmetry evaluation for an interferometric fiber optic gyro coil utilizing a
      bidirectional distributed polarization measurement system.
AB  - We propose a dual-channel measurement system for evaluating the optical path
      symmetry of an interferometric fiber optic gyro (IFOG) coil. Utilizing a
      bidirectional distributed polarization measurement system, the forward and
      backward transmission performances of an IFOG coil are characterized
      simultaneously by just a one-time measurement. The simple but practical
      configuration is composed of a bidirectional Mach-Zehnder interferometer and
      multichannel transmission devices connected to the IFOG coil under test. The
      static and dynamic temperature results of the IFOG coil reveal that its
      polarization-related symmetric properties can be effectively obtained with high
      accuracy. The optical path symmetry investigation is highly beneficial in
      monitoring and improving the winding technology of an IFOG coil and reducing the
      nonreciprocal effect of an IFOG.

PMID- 29047703
TI  - Six-channel multi-wavelength polarization Raman lidar for aerosol and water vapor
      profiling.
AB  - Aerosols and water vapor are important atmospheric components, and have
      significant effects on both atmospheric energy conversion and climate formation.
      They play the important roles in balancing the radiation budget between the
      atmosphere and Earth, while water vapor also directly affects rainfall and other
      weather processes. To further research atmospheric aerosol optical properties and
      water vapor content, an all-time six-channel multi-wavelength polarization Raman
      lidar has been developed at Beifang University of Nationalities. In addition to
      1064, 532, and 355 nm Mie scattering channels, the lidar has a polarization
      channel for 532 nm return signals, a 660 nm water vapor channel, and a 607 nm
      nitrogen detection channel. Experiments verified the lidar's feasibility and
      return signals from six channels were detected. Using inversion algorithms,
      extinction coefficient profiles at 1064, 532 and 355 nm, Angstrom exponent
      profiles, depolarization ratio profiles, and water vapor mixing ratio profiles
      were all obtained. The polarization characteristics and water vapor content of
      cirrus clouds, the polarization characteristics of dusty weather, and the water
      vapor profiles over different days were also analyzed. Results show that the
      lidar has the full-time detection capability for atmospheric aerosol optical
      properties and water vapor profiles, and real-time measurements of aerosols and
      water vapor over the Yinchuan area were realized, providing important information
      for studying the environmental quality and climate change in this area.

PMID- 29047704
TI  - Freeform optical design for a nonscanning corneal imaging system with a convexly
      curved image.
AB  - Most existing techniques that are typically used by specialists to image the
      cornea are based on point, slit, or annular scanning due to a narrow field of
      view. The difficulty in achieving a larger field of view comes from the convex
      shape of the human eyeball. Field curvature for a refractive imaging system with
      positive power is typically negative and thus a concave image surface. In order
      to view the full cornea and sclera with snapshot imaging, we calculate qualified
      two- and three-mirror solutions from Seidel aberration theory. A three-mirror
      solution is further optimized as a high-resolution off-axis imaging system using
      freeform surfaces, which can obtain a full-field tailored image shell without
      scanning. The lateral resolution on the cornea is about 10 MUm with good
      modulation transfer function (MTF) and spot performance. To ease the assembly, a
      monolithic design is achieved with slightly lower resolution, leading to a
      potential mass production solution.

PMID- 29047705
TI  - Radiometric imaging by double exposure and gain calibration.
AB  - Due to low cost and small size, uncooled microbolometer-based thermal focal plane
      arrays are very attractive for radiometry. However, being non-cooled, they suffer
      from temporally and spatially dependent changes that require constant
      calibration. While the gain calibration can be reasonably realized by two-point
      correction, the offset due to internal radiation loads poses a complicated
      calibration scheme. We present a new computational optics approach that
      simplifies the essential calibration for temperature offset. Using two successive
      images of the object taken with different known blur levels, one can eliminate
      the object term from the image-formation equation, resulting in an equation for
      the unknown sensor offset. A general algebraic model is presented for the space
      variant case followed by solutions using both direct inverse method and iterative
      solver. The new scheme allows restoration of the radiometric value within 1%
      error with the direct method, and 0.2% error with the iterative scheme. Account
      of the influence of realistic lens positioning error on restoration accuracy was
      given. Results using direct inverse methods for restoring the radiometric values
      yield restoration error with a good average error of 3.7% and less.

PMID- 29047706
TI  - Experimental optimization of concatenated taper Mach-Zehnder interferometers
      operating in the 1000-1150  nm wavelength range.
AB  - Experimental optimization of all fiber Mach-Zehnder interferometers based on
      concatenated tapers is presented. The experimental optimization was realized by
      the application of the four parameters Taguchi algorithm, and the insertion loss
      of comb filters operating around the 1064 nm wavelength was taken as the
      parameter to be optimized. The out of band losses were reduced from around 2.5 dB
      (43.7%) to a minimum of 0.45 dB (9.84%) in one case, and from 2.9 (48.71%) to 0.4
      dB (8.79%) by using a fixed tapers pair's geometry with 1  mm*1  mm*1  mm of up
      taper length/waist length/down-taper length, respectively, and a waist diameter
      of 40 MUm.

PMID- 29047707
TI  - Micromirrors with controlled amplitude and phase.
AB  - This paper describes the fabrication of circular micromirrors with diameters
      between 50 and 150 MUm with controlled amplitude and phase. Design,
      manufacturing, and characterization method are presented.

PMID- 29047708
TI  - How good is your lens? Assessing performance with MTF full-field displays.
AB  - Modern optical systems achieve incredible resolution and require more thorough
      testing. We present a method of evaluating and displaying the modulation transfer
      function (MTF) of a lens over its full rectangular field of view. The method
      consists of utilizing commercially available MTF test stations to gather data as
      well as custom software to plot the results. Critically, these measurements allow
      the characterization of misaligned systems with much higher accuracy than the
      typical three- or five-field-point MTF measurements yield. Examples are provided
      of both well-centered and poorly centered systems.

PMID- 29047709
TI  - Full-color holographic 3D display using slice-based fractional Fourier transform
      combined with free-space Fresnel diffraction.
AB  - The fractional Fourier transform (FRT) has been used for computing holograms in
      holographic displays due to its continuity of describing wave diffraction in the
      near field and far field. In this study, we propose a method to realize a full
      color holographic 3D display with combined use of the FRT and the free-space
      Fresnel diffraction. A slice-based optical configuration and the calculation
      algorithm of the FRT are proposed for generating phase-only holograms of full
      color 3D objects. Sequential phase-only holograms are generated for reducing the
      speckle noise of reconstructed images by the time-averaging effect. Free-space
      Fresnel diffraction is used for 3D image reconstruction from the generated
      holograms. The relationship between the fractional orders of different color
      channels and the free-space Fresnel diffraction distance is analyzed. Chromatic
      aberrations caused by different wavelengths of RGB lasers are also compensated. A
      full-color holographic display system using a reflective phase-only spatial light
      modulator (SLM) is established. Both the numerical and optical reconstruction
      results demonstrate the feasibility of the proposed method.

PMID- 29047710
TI  - Intrinsic decomposition from a single spectral image.
AB  - In this paper, we present a spectral intrinsic image decomposition (SIID) model,
      which is dedicated to resolve a natural scene into its purely independent
      intrinsic components: illumination, shading, and reflectance. By introducing
      spectral information, our work can solve many challenging cases, such as scenes
      with metameric effects, which are hard to tackle for trichromatic intrinsic image
      decomposition (IID), and thus offers potential benefits to many higher-level
      vision tasks, e.g., materials classification and recognition, shape-from-shading,
      and spectral image relighting. A both effective and efficient algorithm is
      presented to decompose a spectral image into its independent intrinsic
      components. To facilitate future SIID research, we present a public dataset with
      ground-truth illumination, shading, reflectance and specularity, and a meaningful
      error metric, so that the quantitative comparison becomes achievable. The
      experiments on this dataset and other images demonstrate the accuracy and
      robustness of the proposed method on diverse scenes, and reveal that more
      spectral channels indeed facilitate the vision task (i.e., segmentation and
      recognition).

PMID- 29047711
TI  - Sinusoidal phase-modulating laser diode interferometer for wide range
      displacement measurement.
AB  - A sinusoidal phase-modulating laser diode interferometer for wide range
      displacement measurement is proposed. To realize wide range displacement
      measurement, a signal processing method utilizing a look-up table to estimate the
      dynamic value of the effective sinusoidal phase-modulating depth is detailed, and
      the error caused by the residual amplitude modulation and the effective
      sinusoidal phase-modulating depth in wide range displacement measurement can be
      eliminated. It is discussed that the extended measurement range depends on the
      monotone intervals of several specific functions. The simulation and experimental
      results prove that the sinusoidal phase-modulating laser diode interferometer
      with the proposed method could realize centimeter level displacement measurement
      range.

PMID- 29047712
TI  - Inscription of type I and depressed cladding waveguides in lithium niobate using
      a femtosecond laser.
AB  - We describe two types of waveguides (type I and depressed cladding) inscribed in
      lithium niobate using a variable repetition rate (200 kHz-25 MHz), 270 fs
      duration fiber laser. The type I modification-based waveguides have propagation
      losses in the range from 1.2 to 10 dB/cm at 1550 nm, depending on experimental
      parameters. These waveguides are not permanent; they deteriorate over time. Such
      deterioration of waveguides can be slowed down from 30 days to 100 days by pre
      annealing the samples and by writing at a 720 kHz laser repetition rate. The
      propagation losses measured at 1550 nm show significant improvement for pre
      annealed samples. The depressed cladding-inscribed waveguides are permanent, but
      the propagation loss depends on the number of damage tracks. A track separation
      of ~1  MUm between adjacent damage tracks yields the lowest propagation loss of
      0.5 dB/cm at 1550 nm for a 40 MUm diameter waveguide. We observe multimode
      guidance for sizes in the range of 20-80 MUm in these waveguide structures at
      1550 nm. Their crystalline nature is found to remain intact, as inferred from
      second-harmonic generation within the waveguide region.

PMID- 29047713
TI  - Numerical method based on transfer function for eliminating water vapor noise
      from terahertz spectra.
AB  - Water vapor noise in the air affects the accuracy of optical parameters extracted
      from terahertz (THz) time-domain spectroscopy. In this paper, a numerical method
      was proposed to eliminate water vapor noise from the THz spectra. According to
      the Van Vleck-Weisskopf function and the linear absorption spectrum of water
      molecules in the HITRAN database, we simulated the water vapor absorption
      spectrum and real refractive index spectrum with a particular line width. The
      continuum effect of water vapor molecules was also considered. Theoretical
      transfer function of a different humidity was constructed through the theoretical
      calculation of the water vapor absorption coefficient and the real refractive
      index. The THz signal of the Lacidipine sample containing water vapor background
      noise in the continuous frequency domain of 0.5-1.8 THz was denoised by use of
      the method. The results show that the optical parameters extracted from the
      denoised signal are closer to the optical parameters in the dry nitrogen
      environment.

PMID- 29047714
TI  - Frequency domain approach to the steady state and stability analysis of dual
      injection-locked optoelectronic oscillators.
AB  - A frequency domain algorithm is proposed for deriving all of the possible steady
      state modes of dual injection-locked optoelectronic oscillators (DIL-OEOs),
      corresponding to the detailed system parameters, such as the fiber lengths, small
      signal open loop gains, radio frequency filters' bandwidths, phase shifting
      values, and injection parameters. It is shown that some or all of the modes
      computed by the new approach may be unstable; these are just mathematical
      solutions of the steady state equations. Therefore, it is necessary to check the
      stability of these modes. A stability analysis approach is proposed, which is
      based on simulating the slowly varying time domain dynamic governing the
      perturbation variables. The steady state and stability analysis approaches enable
      one to predict the required injection parameters for having a reliable steady
      state injection-locked mode in the DIL-OEO system. The new method requires a much
      smaller runtime compared to the corresponding time domain methods. In addition,
      it avoids many simplifying assumptions of the corresponding frequency domain
      approaches presented in the literature. The validities of the steady state and
      stability analysis methods are verified by comparing their results with full time
      domain integrations and with other predictions regarding the required injection
      parameters for phase locking, as presented in the literature.

PMID- 29047715
TI  - Performance analysis of zinc oxide-implemented lossy mode resonance-based optical
      fiber refractive index sensor utilizing thin film/nanostructure.
AB  - A detailed primeval study on the lossy mode resonance (LMR) behavior of zinc
      oxide (ZnO)-coated optical fiber as a refractive index sensor is carried out.
      Theoretical evaluation predicts ZnO as a good choice for the LMR-based chemical
      and gas sensor operating in the visible region of the electromagnetic spectrum.
      To confirm, the optical fiber probe has been fabricated with an optimized film
      thickness of ZnO over an unclad core of fiber and characterized. Additionally, an
      LMR-based nanosensor platform utilizing ZnO has also been investigated to find
      the compatibility of a nanotechnological LMR sensor. The nanostructured LMR
      sensors have shown enhanced sensitivity in comparison to a bulk layered probe.

PMID- 29047716
TI  - Dynamical range and stability enhancement in electrically fused microknot optical
      resonators.
AB  - Microknot resonators (MKRs), locally fused using a two-probe technique, have
      exhibited significantly improved optical performance and mechanical stability.
      They have been operated with low losses both in situ and as transferred devices.
      We found consistently more than threefold dynamical range enhancement, which
      remained stable in time, in electrically fused MKRs. These devices can be
      harbored in next-generation optical sensors, actuators, and optomechanical
      applications incorporating MKR-assisted microstructures taking advantage of this
      simple and robust fusing technique.

PMID- 29047718
TI  - Beam splitter and router via an incoherent pump-assisted electromagnetically
      induced blazed grating.
AB  - We propose a scheme for a beam splitter and a beam router via an
      electromagnetically induced blazed grating in a four-level double-Lambda system
      driven by an intensity-modulated coupling field and an incoherent pump field. The
      blazed grating relies on the incoherent pump process, which helps in inducing
      large refractivity with suppressed absorption or even gain. Consequently, the
      weak probe beam can be effectively deflected with high diffraction efficiency,
      and, meanwhile, its energy is amplified. When using an intensity mask with two
      symmetric domains in the coupling field, the presented blazed grating provides
      the possibility of a symmetric beam splitter. The diffraction efficiency and
      diffraction order of the gratings are sensitive to the intensity of the coupling
      field, and, thus, the gratings can function as a tunable asymmetric beam splitter
      or a beam router, which distributes the probe field into different spatial
      directions. Therefore, the proposed scheme may have potential applications in
      optical communication and networking.

PMID- 29047717
TI  - Broadening the reflection bandwidth of polymer-stabilized cholesteric liquid
      crystal via a reactive surface coating layer.
AB  - We report a method of broadening the reflection bandwidth of polymer-stabilized
      cholesteric liquid crystal (PSCLC). The top substrate was consecutively coated
      with a polyimide (PI) and a reactive mesogen (RM) layer, while the bottom
      substrate was coated with only PI. We exposed the top substrate with the RM
      coating to UV light. The reflection bandwidth of the PSCLC samples where the top
      substrate was over-coated with RM was significantly broader than the samples
      where both substrates were coated with PI. In addition to the effect of the UV
      intensity gradient, the RM-coated top substrate has a chemical affinity to bulk
      RM, promoting formation of the pitch gradient and broadening the reflection
      bandwidth in the sample.

PMID- 29047720
TI  - Uncertainty analysis for the determination of B4C optical constants by angle
      dependent reflectance measurement for 40  nm to 80  nm wavelength.
AB  - The index of refraction and the extinction coefficient for thin films of boron
      carbide were determined by angle-dependent reflectance measurements in the vacuum
      ultraviolet spectral range. The numerical approximation was done using transfer
      matrix formalism in combination with particle swarm optimization for the fitting
      algorithm. By this, not only for the reflectance measurement but also for the
      numerical approximation, a profound uncertainty budget was developed. This
      includes possible effects due to contamination and intermediate layers. Thus it
      was possible to establish a method for determination of n and k with reliable and
      highly traceable uncertainties, and to significantly improve the consistency of
      existing data required for current developments in optical technology.

PMID- 29047719
TI  - Light trapping for photovoltaic cells using polarization-insensitive angle
      selective filters under monochromatic illumination.
AB  - We have proposed a light-trapping concept for photovoltaic (PV) cells under
      monochromatic illumination with restricted incident angles. We employed a
      configuration consisting of a shortpass filter (SPF) on the front surface and a
      diffuse reflector on the rear surface of the cell. The SPF was designed so that
      it functioned as a polarization-insensitive angle-selective filter. We fabricated
      30-80-MUm-thick crystalline silicon samples for incident angles changing within
      30 degrees , and analyzed the measured results using a ray-trace simulation with
      the Monte Carlo method. The ratio of the absorbed intensity to the 1064 nm
      illumination intensity was 0.69-0.85, which was higher than those equipped with
      antireflection coatings instead of the SPFs by 0.19-0.13. Thus, we have proven
      the light-trapping concept of the SPF/diffuse reflector configuration for
      monochromatic illumination. The PV cells could be applied to wireless power
      supply, in particular from solar-pumped lasers.

PMID- 29047721
TI  - Bessel function expansion to reduce the calculation time and memory usage for
      cylindrical computer-generated holograms.
AB  - This study proposes a method to reduce the calculation time and memory usage
      required for calculating cylindrical computer-generated holograms. The wavefront
      on the cylindrical observation surface is represented as a convolution integral
      in the 3D Fourier domain. The Fourier transformation of the kernel function
      involving this convolution integral is analytically performed using a Bessel
      function expansion. The analytical solution can drastically reduce the
      calculation time and the memory usage without any cost, compared with the
      numerical method using fast Fourier transform to Fourier transform the kernel
      function. In this study, we present the analytical derivation, the efficient
      calculation of Bessel function series, and a numerical simulation. Furthermore,
      we demonstrate the effectiveness of the analytical solution through comparisons
      of calculation time and memory usage.

PMID- 29047722
TI  - Frequency domain staring pump-probe technique for Brillouin gain/loss spectrum
      measurement.
AB  - We propose and demonstrate a modified frequency sweep-free pump-probe technique,
      called staring pump-probe technique (SPPT) for Brillouin signal measurement based
      on stimulated Brillouin scattering (SBS). The SPPT retains the advantages of
      conventional pump-probe technique, and employs a simple device and low-cost
      measurement system. Moreover, the Brillouin gain/loss spectrum (BGS/BLS) can be
      reconstructed without frequency-sweep, thus greatly improving the measurement
      speed. In this paper, an approximate flat-top spectrum broadened probe light is
      introduced through distributed feedback laser by direct modulation. The BGS/BLS
      is reconstructed with the enhanced signal-noise ratio of approximately 21 dB/23
      dB. This technique has a potential application for some Brillouin scattering
      involved Brillouin frequency shift measurement.

PMID- 29047724
TI  - Asymmetric transmission of obliquely intersecting nanoslit arrays in a gold film.
AB  - Asymmetric transmission (AT) has significant applications in optical polarization
      control. In this paper, we propose a kind of periodic nanoslit rather than the
      protruding planar structures, such as G-shaped structure and coupled split-ring
      resonators, to realize the AT effect. The planar periodic obliquely intersecting
      nanoslits (OINs) in the gold film, composed of gratings with an infinite length
      and tilted nanoslits with a finite length, are proposed to realize the AT effect
      by performing the finite element method. Obvious dips in the AT spectra result
      from the circular localized surface plasmon resonance around the two terminals of
      the tilted nanoslits and from the surface plasmon polariton resonances on the
      film and in the gratings or tilted nanoslits. In addition, the AT effect strongly
      depends on the geometric parameters of the OINs. The film can be straightly
      powered on as an in-plane electrical conductor, which broadens its applications
      in optoelectronic devices. Overall, these results are beneficial in designing
      devices to achieve AT for polarization transformation.

PMID- 29047723
TI  - High-performance surface-enhanced Raman scattering substrate prepared by self
      assembling of silver nanoparticles into the nanogaps of silver nanoislands.
AB  - We report an effective and simple method to further enhance the surface-enhanced
      Raman scattering (SERS) by silver (Ag) nanoparticles (AgNPs) self-assembling into
      the nanogaps of an Ag nanoisland (AgNIs). The AgNIs prepared by dewetting of Ag
      film created a nanorough surface, which induced the Ag nanoparticles to regularly
      deposit into the nanogaps. AgNPs and AgNIs samples were also prepared for
      comparative analysis. Their SERS activities were investigated theoretically and
      experimentally. Experimental enhancement factors (EFs) for AgNPs, AgNIs, and
      AgNPs decorated AgNIs substrate (AgNPs-AgNIs) were ~107, ~106, ~108,
      respectively, with relative standard deviation (RSD) of 66.1%, 12.9%, and 13.2%.
      Remarkable enhancement (EF~108) and excellent reproducibility (RSD=13.2%)
      indicated the AgNPs-AgNIs had a high potential in practical application.
      Electromagnetic simulation using COMSOL Multiphysics demonstrated that the
      additional enhancement of the SERS effect could be mainly attributed to the
      improvement of the local electromagnetic field. Moreover, the deposition process
      of Ag nanoparticles was analyzed in detail to understand the reproducibility of
      AgNPs-AgNIs.

PMID- 29047725
TI  - Optimal modified lateral shearing interferometer for submicro-defects measurement
      of transparent objects.
AB  - Transparent optical components, which are required for high-precision and high
      performance, are made by a plastic injection molding method. This can cause inner
      defects to appear because of the difference in cooling rate and pressure.
      However, submicron inner defects, caused by the refractive index error, are
      extremely difficult to determine. Thus, digital holographic microscopy based on
      an optimal modified lateral shearing interferometer is proposed. This is to
      measure submicron defects in transparent objects, such as a defective microlens.
      In addition, the optimal lateral shearing distance is proposed to efficiently
      remove duplicate images. Optical experiments using the suggested lateral shearing
      interferometer are presented, and the experimental results with a test microlens
      confirm the feasibility of the proposed method.

PMID- 29047726
TI  - Nonstationary optical transfer functions of underwater imaging systems.
AB  - Optical transfer functions of underwater imaging systems employing narrow pulses
      or sinusoidally modulated beams for image formation are studied. A modified Monte
      Carlo technique allowing for direct statistical modeling of these functions
      accounting for temporal dispersion is proposed and implemented. The optical
      transfer functions are calculated for various modulation frequencies of the
      illumination beam and for the case of pulsed illumination. The employment of high
      frequency sinusoidal or pulsed modulation with consistent processing of the
      received signal is shown to significantly increase the contrast sensitivity of
      underwater imaging systems as compared with systems with stationary illumination.

PMID- 29047728
TI  - Narrowband transparent absorbers based on ellipsoidal nanoparticles.
AB  - In this paper, we propose the design of an optical device that is able to
      selectively absorb impinging light in a desired frequency range while being
      almost completely transparent outside this range. The proposed absorber is a
      variant of the optical Salisbury screen we recently proposed [Opt. Lett.41, 3383
      (2016)OPLEDP0146-959210.1364/OL.41.003383] but, differently from this earlier
      version, is transparent for any electromagnetic wave whose frequency is outside
      the absorption spectrum. Such an absorber also exhibits excellent performance in
      terms of angular bandwidth and may find application in all scenarios where
      narrowband absorption is required, such as for light filters or digital sensors.
      Full-wave simulations confirming the effectiveness of the proposed absorber as
      well as its robustness toward geometrical defects are provided.

PMID- 29047727
TI  - Performance of Co/Ti multilayers in a water window soft x-ray regime.
AB  - The DC magnetron sputter grown Co/Ti multilayers, with ultra-low bi-layer
      thicknesses and with Co layers deposited under mixed ambience of argon and dry
      air, have been investigated for use in the water window soft x-ray regime of 23
      44 A. Initially, deposition parameters have been optimized for obtaining smooth
      and continuous low thickness Co and Ti single-layer films, and, then, multilayers
      with five bi-layers of various bi-layer thicknesses were deposited. The samples
      have been primarily characterized by the grazing incidence x-ray reflectivity
      (GIXR) measurements with a hard x-ray laboratory source. Subsequently, a set of
      multilayers with an increasing number of bi-layers has been deposited with a
      constant bi-layer thickness of 42 A. GIXR results show that hard x-ray
      reflectivity at the first Bragg peak is maximum for the 20 bi-layer sample,
      beyond which the reflectivity decreases. Finally, the samples with the most
      promising hard x-ray GIXR have been used for soft x-ray reflectivity measurement
      with synchrotron radiation, and ~2.5% peak reflectivity has been obtained in the
      multilayer sample at a 30.7 A wavelength for a 21.5 degrees  grazing angle of
      incidence. The fitting results for both hard and soft x-ray reflectivities have
      been thoroughly investigated to find out the cause of the saturation of
      reflectivity with the increase in the number of bi-layers.

PMID- 29047729
TI  - Quantification and analysis of color stability based on thermal transient
      behavior in white LED lamps.
AB  - We present measurement and analysis of color stability over time for two
      categories of white LED lamps based on their thermal management scheme, which
      also affects their transient lumen depreciation. We previously reported that
      lumen depreciation in LED lamps can be minimized by properly designing the heat
      sink configuration that allows lamps to reach a thermal equilibrium condition
      quickly. Although it is well known that lumen depreciation degrades color
      stability of white light since color coordinates vary with total lumen power by
      definition, quantification and characterization of color shifts based on thermal
      transient behavior have not been previously reported in literature for LED lamps.
      Here we provide experimental data and analysis of transient color shifts for two
      categories of household LED lamps (from a total of six lamps in two categories)
      and demonstrate that reaching thermal equilibrium more quickly provides better
      stability for color rendering, color temperature, and less deviation of color
      coordinates from the Planckian blackbody locus line, which are all very important
      characterization parameters of color for white light. We report for the first
      time that a lamp's color degradation from the turn-on time primarily depends on
      thermal transient behavior of the semiconductor LED chip, which experiences a
      wavelength shift as well as a decrease in its dominant wavelength peak value with
      time, which in turn degrades the phosphor conversion. For the first time, we also
      provide a comprehensive quantitative analysis that differentiates color
      degradation due to the heat rise in GaN/GaInN LED chips and subsequently the
      boards these chips are mounted on-from that caused by phosphor heating in a white
      LED module. Finally, we briefly discuss why there are some inevitable trade-offs
      between omnidirectionality and color and luminous output stability in current
      household LED lamps and what will help eliminate these trade-offs in future lamp
      designs.

PMID- 29047730
TI  - Comparative study between polarimetric and intensity-based surface plasmon
      resonance sensors in the spectral mode.
AB  - There is a debate on whether phase measurement in surface plasmon resonance (SPR)
      sensors give better resolution than intensity measurement. In this work, we show
      that each one of the modes can give better resolution depending on the metal
      layer thickness chosen, as well as the available noise levels in the system. We
      propose a three point polarimetric approach to extract the ellipsometric
      parameters and phase information in the spectral mode. It is shown that the
      polarimetric measurement at its optimal thickness range gives up to seven-fold
      higher resolution than the intensity, especially at noise levels of off the shelf
      spectrometers. When noise levels are very low, the resolution in the two modes
      becomes nearly equal. The same is true when considering the whole SPR curve
      rather than single point detection. However, it is clearly shown both
      experimentally and theoretically that the polarimetric measurements at their
      optimal range give much better resolution than the intensity.

PMID- 29047731
TI  - Catadioptric interfaces for designing VLC antennae.
AB  - This paper presents a model to design bi-aspherical catadioptric lenses with
      limited image diffraction. A first refractive Cartesian oval surface that does
      not introduce any spherical aberration is used. When total internal reflection
      occurs, this surface can also be simultaneously used as a mirror. The reflective
      characteristics of Cartesian ovals are also well described in this paper. The
      theoretical work described here can considerably reduce computing time in optical
      system design. This model is applied to examples of antennae design for visible
      light communications (VLC).

PMID- 29047732
TI  - Generation of perfect polarization vortices using combined gratings in a single
      spatial light modulator.
AB  - Perfect polarization vortices (PPVs) are a type of vector beam with a diameter
      independent of the polarization order. In this paper, an experimental method is
      proposed to generate PPVs with an anisotropic polarization distribution. First, a
      specially designed hologram is generated on a liquid-crystal spatial light
      modulator (SLM) to obtain Bessel-Gaussian (BG) beams. Second, the BG beams are
      transformed into PPVs in the Bessel region by an interferometer, which includes a
      polarized beam splitter, two reflectors, and several lenses. In our experiment,
      PPVs with adjustable polarization orders and diameters are obtained by generating
      various combined holograms on the SLM.

PMID- 29047733
TI  - Realization of an O-waveband laser based on cascaded stimulated Raman scattering
      of microspheres.
AB  - We report an experimental realization of five-order Stokes stimulated Raman
      scattering lasing in silica microspheres pumped by a 1030 nm continuous-wave
      laser. The wavelength of the Stokes Raman laser is extended to 1348.55 nm, which
      is located in the second low loss window of the optical fiber. It has potential
      applications in the wavelength converter and Raman amplifier in O-waveband
      optical communication. The minimum pump power is about 50 MUW when the first
      order Stokes Raman laser can be observed.

PMID- 29047734
TI  - Evaluation of a HgCdTe e-APD based detector for 2  MUm CO2 DIAL application.
AB  - Benefiting from close to ideal amplification properties (high gain, low dark
      current, and low excess noise factor), HgCdTe electron initiated avalanche
      photodiode (e-APD) technology exhibits state of the art sensitivity, thus being
      especially relevant for applications relying on low light level detection, such
      as LIDAR (Light Detection And Ranging). In addition, the tunable gap of the Hg1
      xCdxTe alloy enables coverage of the short wavelength infrared (SWIR) and
      especially the 2 MUm spectral range. For these two reasons, a HgCdTe e-APD based
      detector is a promising candidate for future differential absorption LIDAR
      missions targeting greenhouse gas absorption bands in SWIR. In this study, we
      report on the design and evaluation of such a HgCdTe e-APD based detector. The
      first part focuses on detector architecture and performance. Key figures of merit
      are: 2.8 MUm cutoff wavelength, 200 MUm diameter almost circular sensitive area,
      185 K operating temperature (thermo-electric cooling), 22 APD gain (at 12 V
      reverse bias), 360  kOmega transimpedance gain, and 60  fWHz-0.5 noise equivalent
      power (at 12 V reverse bias). The second part presents an analysis of atmospheric
      LIDAR signals obtained by mounting the HgCdTe e-APD based detector on the 2 MUm
      differential absorption LIDAR developed at the Laboratoire de Meteorologie
      Dynamique and dedicated to CO2 monitoring. Discussion emphasizes random and
      systematic errors in LIDAR measurements regarding breadboard detector
      characterization. In particular, we investigate the influence of parasitic tails
      in detector impulse response on short range DIAL measurements.

PMID- 29047735
TI  - Quasi-single-crystal-fiber acousto-optic Q-switched tandem dual Nd:YVO4 thin rods
      laser.
AB  - An 888 nm pumped quasi-single-crystal-fiber (quasi-SCF) acousto-optic Q-switched
      Nd:YVO4 laser is experimentally demonstrated for the first time, where two
      closely jointed crystals with different side surface styles serve as a long thin
      medium to improve the pump absorption and alleviate thermal load. In continuous
      wave operation, the highest output power can reach 38.7 W with corresponding
      optical-optical efficiency of 0.492. In Q-switched operation, the optical-optical
      efficiency increases from 0.347 to 0.476 and pulse duration varies from 15 ns to
      32.8 ns when pulse repetition frequency increases from 30 kHz to 100 kHz. The
      measured beam quality factors M2 are 1.018 and 1.030, respectively. The quasi-SCF
      scheme enjoys the advantage of sufficient pump absorption and reduced amplified
      spontaneous emission, which is promising for further applications in high-power
      lasers.

PMID- 29047736
TI  - Biconic White multipass cell design based on a skew ray-tracing model.
AB  - A biconic White multipass cell (bi-WMPC), designed as a compact, zero-geometrical
      loss, anastigmatic optical system, capably used with an extended divergent
      source, is proposed. First, a skew ray-tracing model is developed for a
      conventional White-type multipass cell (WMPC), based on which the astigmatism is
      calculated, together with its sensitivity coefficients in relation to all
      important optical structural parameters in various configurations. Next, a
      generalized bi-WMPC is designed to suppress the astigmatism, which leads to much
      smaller reflection spots on the field mirror compared to the conventional design.
      The demonstration of an optimized bi-WMPC initialized from a commercial WMPC (52
      pass with a 0.8 m base length) suggests a 53 fold reduction of the wavefront
      error value from 79.187lambda to 1.493lambda, as well as the path-to-volume ratio
      (PVR) increase from 20.8 to 35.2 m/L. These improvements are critical for the
      design of a compact WMPC with a path length of tens to hundreds of meters.
      Presently developed skew ray-tracing models for a WMPC can also be applied to
      other freeform surfaces to further compensate the inherent aberrations induced by
      multiple off-axis reflections.

PMID- 29047737
TI  - Determination of the laser beam quality factor (M2) by stitching quadriwave
      lateral shearing interferograms with different exposures.
AB  - A complete complex amplitude reconstruction method for the determination of the
      laser beam quality factor M2 based on the multiple exposure of a quadriwave
      lateral shearing interferometer (QWLSI) is presented. The theoretical analysis
      and simulation of the influence of the information in the small signal area on
      the calculation of the M2 factor is provided. The experimental results
      demonstrate that the new method can be an accurate means to measure the M2
      factor. The proposed method can avoid the influence of phase inaccuracy in the
      small signal area of the interferogram, during the measurement of the M2 factor.

PMID- 29047738
TI  - Magnesium diboride (MgB2) as a saturable absorber for a ytterbium-doped Q
      switched fiber laser.
AB  - Magnesium diboride (MgB2) is a well-known superconductor at temperatures below 39
      K. At higher temperatures, it behaves as a lossy material. In this paper, we
      examine the performance of MgB2 nano-particles as saturable absorber in a
      ytterbium-doped fiber ring laser at room temperature: we show that the nano
      particles can produce pulses between 200 and 1700 ns. The dynamics of the
      saturable absorber are both examined as a stand-alone saturable absorber and in
      combination with an acousto-optic modulator. We believe, to the best of our
      knowledge, that this is the first time that MgB2 is used as a saturable absorber
      in a Q-switched laser.

PMID- 29047739
TI  - Temperature-dependent diffuse reflectance spectroscopy of plasma-sprayed Cr-doped
      alpha-alumina using supercontinuum laser illumination and CO2 laser heating.
AB  - This study presents results for the high-temperature (up to 1550 K) optical
      properties of polycrystalline Cr-doped alpha-alumina materials. Diffuse
      reflectance spectra in the wavelength range of 510-840 nm are presented as a
      function of temperature to illustrate changes to the optical behavior of these
      materials including a previously unreported thermally activated splitting of the
      U-band absorption (A24->T24) in octahedrally coordinated Cr3+. Measurements were
      made using a unique laser-based approach for high-temperature solid-state
      spectroscopy, involving front-side supercontinuum laser illumination and back
      side CO2 laser heating. This approach required development of samples that could
      withstand related thermal stresses, and measurements were made on plasma-sprayed,
      Cr-doped alpha-alumina monoliths. Measured spectra are interpreted, in part,
      using published optical spectra for ruby; agreement between results here with
      those obtained using more traditional methods serves to validate the measurement
      methods used for this work.

PMID- 29047740
TI  - Experimental investigation on aero-optics of supersonic turbulent boundary
      layers.
AB  - Nanoparticle-based planar laser scattering was used to measure the density
      distribution of the supersonic (Ma=3.0) turbulent boundary layer and the optical
      path difference (OPD), which is quite crucial for aero-optics study. Results were
      obtained using ray tracing. The influences of different layers in the boundary
      layer, turbulence scales, and light incident angle on aero-optics were examined,
      and the underlying flow physics were analyzed. The inner layer plays a dominant
      role, followed by the outer layer. One hundred OPDrms of the outer layer at
      different times satisfy the normal distribution better than that of the inner
      layer. Aero-optics induced by the outer layer is sensitive to the filter scale.
      When induced by the inner layer, it is not sensitive to the filter scale. The
      vortices with scales less than the Kolmogorov scale (=46.0  MUm) have little
      influence on the aero-optics and could be ignored; the validity of the smallest
      optically active scale (=88.1  MUm) proposed by Mani is verified, and vortices
      with scales less than that are ignored, resulting in a 1.62% decay of aero
      optics; the filter with a width of 16-grid spacing (=182.4  MUm) decreases OPDrms
      by 7.04%. With the increase of the angle between the wall-normal direction and
      the light-incident direction, the aero-optics becomes more serious, and the
      difference between the distribution of the OPDrms and the normal distribution
      increases. The difficulty of aero-optics correction is increased. Light tilted
      toward downstream experiences more distortions than when tilted toward upstream
      at the same angle relative to the wall-normal direction.

PMID- 29047741
TI  - Electric field sensing with liquid-crystal-filled slot waveguide microring
      resonators.
AB  - We consider the operation principles of the sensor of an external electric field
      on the bases of microring resonators that consist of bent-strip waveguides with
      vertical or horizontal slots filled with nematic liquid crystal. The mode-field
      distribution and dispersion parameters of the bent-slot waveguides are calculated
      by using the algorithm based on the method of lines. The influence of the
      waveguide and microresonator structure (slot width, position and orientation,
      microresonator radius, etc.) on the sensor sensitivity is analyzed.

PMID- 29047742
TI  - Mode-locked laser with a repetition rate of 17.6  THz.
AB  - In 2001, a concept was proposed to generate mode-locked ultrashort laser pulses
      with a repetition rate in excess of 10 THz [Phys. Rev. Lett.87, 223901
      (2001)PRLTAO0031-900710.1103/PhysRevLett.87.223901], which has not been
      demonstrated so far. In the present research, the concept is experimentally
      demonstrated using a dispersion-compensated high-finesse cavity filled with
      hydrogen gas. Second-order intensity autocorrelation is used for distinguishing
      two cases with and without mode-locking as well as for characterization of the
      temporal profile. Mode-locked sub-30-fs pulses with a repetition rate of 17.6 THz
      are synthesized by continuous-wave laser lines generated via stimulated Raman
      scattering and four-wave Raman mixing induced in the high-finesse cavity.

PMID- 29047743
TI  - Subpixel reconstruction for single-shot phase imaging with coded diffraction.
AB  - We present an algorithm for reconstructing an object complex field with
      resolution below that of an image sensor (subpixel resolution) in single-shot
      diffractive imaging with coded diffraction. The algorithm employs subpixel phase
      retrieval and sparse regularization based on compressive sensing. This is useful
      for high-speed or high-sensitivity imaging using an image sensor with a low pixel
      count and/or a large pixel size. We experimentally demonstrated the proposed
      method with two types of moving objects.

PMID- 29047744
TI  - Full-color holographic 3D display using slice-based fractional Fourier transform
      combined with free-space Fresnel diffraction: erratum.
AB  - We have addressed some errors in our recent work [Appl. Opt.56, 5668
      (2017)APOPAI0003-693510.1364/AO.56.005668]. Especially, we note that the formulae
      for reconstruction of phase-only holograms are different from the formulae for
      amplitude holograms. So Eqs. (9) and (12) must be modified.

PMID- 29047745
TI  - Demonstration of a 150-kW-peak-power, 2-GHz-linewidth, 1.9-MUm fiber gas Raman
      source.
AB  - We report here for the first time, to the best of our knowledge, a 100-kW-peak
      power, GHz-linewidth, sub-nanosecond, 1.9-MUm laser source by gas stimulated
      Raman scattering (SRS) in hollow-core fiber. A H2-filled, anti-resonance, hollow
      core fiber is pumped with a sub-nanosecond, high-peak-power, 1064-nm microchip
      laser, generating a 1908-nm Stokes wave by vibrational SRS of H2 molecules. A
      maximum peak power of about 150 kW (average power 55 mW, pulse energy 55 MUJ) is
      achieved with a 1.4-m fiber length and only 3 bar H2 pressure. The maximum
      quantum efficiency is about 54%, and the corresponding slope efficiency is about
      37%. The linewidth of the Stokes wave is about 2 GHz, which decreases about 1-2
      orders compared with the rare-earth-doped fiber lasers of the same peak-power
      level. Operation close to atmospheric pressure makes it more convenient in future
      applications. If a tunable pump laser is used, a high-peak-power, narrow
      linewidth, broadly tunable, 2-MUm fiber laser source can be easily achieved.

PMID- 29047746
TI  - Building texture acquisition and processing based on an unmanned airship low
      altitude aerial survey system.
AB  - The traditional oblique cameras cannot self-calibrate to complete the three
      dimensional (3D) modeling to meet high mapping accuracy requirements. We propose
      an oblique combined camera system, called a texture camera, aboard an unmanned
      airship that can simultaneously obtain a single vertical image and four oblique
      images of an object. The images acquired by this self-calibrating camera system
      can be used to produce traditional products on a large scale. Additionally, they
      can be used to accurately determine the orientation elements of each individual
      camera, which are essential for 3D modeling. With the methods of building texture
      extraction and color optimization, the processing of 3D building texture can be
      completed automatically and quickly. Experimental results show that our strategy
      can meet the precision requirements of an aerial survey topographic map with a
      scale of 1:500, and that the building facade textures are complete and clear.
      Using this texture camera system, 3D building models with a high mapping accuracy
      and realistic textures can be established.

PMID- 29047747
TI  - Wavelength and concentration-dependent optical constants of NaCl, KCl, MgCl2,
      CaCl2, and Na2SO4 multi-component mixed-salt solutions.
AB  - The optical constants of sodium chloride (NaCl), potassium chloride (KCl),
      magnesium chloride (MgCl2), calcium chloride (CaCl2) and sodium sulfate (Na2SO4)
      solutions at weight fractions ranging from 0 to 16.6667% are measured by the
      combined ellipsometry-transmission method in the spectral range 0.3-1.0 MUm. In
      the combined method, a modified ellipsometry method is used to measure the
      refractive indices of liquids, and then the transmission method is conducted to
      obtain the extinction coefficients using the refractive indices obtained by the
      ellipsometry method. The experimental refractive indices of these binary
      solutions are utilized to obtain a mole-fraction weighted mixing rule, which
      relates the refractive index of multi-component mixed-salt solutions to the
      wavelength and concentration of each component. The effects of wavelength and
      concentration are taken into account by empirical expressions of the Lorentz
      Lorenz formulized molar refraction. A mole-fraction weighted linear combined
      mixing rule is proposed to study the wavelength and concentration-dependent
      extinction coefficients of mixed-salt solutions. The optical constants of NaCl
      KCl and NaCl-Na2SO4 ternary solutions, NaCl-KCl-CaCl2 quaternary solutions, and
      NaCl-KCl-MgCl2-CaCl2-Na2SO4 multi-component solutions are measured to verify the
      mixing rules. The results show that the optical constants calculated based on the
      mixing rules are in good agreement with experimental data, which demonstrate the
      feasibility of the proposed mixing rules. As the experimental analysis indicates,
      both the refractive indices and the extinction coefficients of the saline
      solutions increase with solute concentrations in the spectral range 0.3-1.0 MUm.

PMID- 29047748
TI  - Error analysis of large-diameter subaperture stitching Fresnel diffractive
      elements.
AB  - Image quality is dramatically influenced by the stitching errors in a large
      diameter stitching Fresnel lens. In this paper, we studied three kinds of errors
      that can cover all stitching errors in a Cornwell deployed Fresnel lens. In
      particular, a 300-mm-diameter, three-belt deployed Fresnel diffractive lens was
      simulated to investigate the stitching error. The star test and the resolution
      board test experiments were conducted, and the experimental results fit the
      simulation results. This means that our error analysis theory and simulation
      method are efficient and accurate and could be used to guide future super-large
      aperture stitching.

PMID- 29047749
TI  - Lidar equation inversion methods and uncertainties in measuring fugitive
      particulate matter emission factors.
AB  - Measurements from two field campaigns that employed a micropulse lidar are used
      to compare the near-end and the far-end lidar equation inversion methods for
      estimating emission factors (EFs) of particulate matter (PM) from three types of
      anthropogenic fugitive sources: vehicles moving on unpaved roads, open burning,
      and open detonation. As optical depth increased from 0 to 2, relative EF
      uncertainty increased from 54% to 300% using the near-end method and decreased
      from 69% to 42% using the far-end method. To the best of our knowledge, this
      research is the first to use field measurements to compare results from these
      methods for anthropogenic PM plumes and quantify their uncertainties.

PMID- 29047751
TI  - Comparative analysis of gradient-field-based orientation estimation methods and
      regularized singular-value decomposition for fringe pattern processing.
AB  - Fringe orientation is an important feature of fringe patterns and has a wide
      range of applications such as guiding fringe pattern filtering, phase unwrapping,
      and abstraction. Estimating fringe orientation is a basic task for subsequent
      processing of fringe patterns. However, various noise, singular and obscure
      points, and orientation data degeneration lead to inaccurate calculations of
      fringe orientation. Thus, to deepen the understanding of orientation estimation
      and to better guide orientation estimation in fringe pattern processing, some
      advanced gradient-field-based orientation estimation methods are compared and
      analyzed. At the same time, following the ideas of smoothing regularization and
      computing of bigger gradient fields, a regularized singular-value decomposition
      (RSVD) technique is proposed for fringe orientation estimation. To compare the
      performance of these gradient-field-based methods, quantitative results and
      visual effect maps of orientation estimation are given on simulated and real
      fringe patterns that demonstrate that the RSVD produces the best estimation
      results at a cost of relatively less time.

PMID- 29047750
TI  - Vector representation of spectrophotometric measurements of medium composition.
AB  - A rigorous theoretical description of the standard spectrophotometric method for
      determining medium composition is given using a vector representation of measured
      signals. Further modifications, methods of orthogonal optical absorption
      spectroscopy (OOAS) and differential optical absorption spectroscopy (DOAS), are
      also substantiated. It is shown that the conventional criterion, the difference
      between the measured spectrum and the spectrum simulated on the basis of
      calculations, does not serve as an indicator of quality of the latter. The main
      problem of metrological assurance of the methods-estimating uncertainties of
      calculation results-is discussed in detail. Inability to quantify the quality of
      approximation of some contributions to measured signals appears to be a
      significant disadvantage of the DOAS procedure.

PMID- 29047752
TI  - Interferometric measurement of temporal behavior of linear birefringence with
      extended range.
AB  - A heterodyne interferometer is developed to measure the static and temporal
      behaviors of birefringence of a liquid crystal variable retarder. The
      interferometer is designed based on the analysis of the polarization state of a
      coherent wave. Since the optical components of the interferometer are fixed
      without any adjustment, the phase retardation and the azimuthal angle of a liquid
      crystal variable retarder is measured independently in real time, where the
      environmental perturbations and common mode noises can be reduced. From the
      analysis and experimental demonstrations, the phase retardation can be determined
      in the [0, 4pi] range. Meanwhile, the orientational variation of the azimuthal
      angle of the optic axis is found.

PMID- 29047753
TI  - Real-time reference-based dynamic phase retrieval algorithm for optical
      measurement.
AB  - To study dynamic behaviors of a phenomenon, measuring the evolving field of a
      specimen/material/structure is required. Optical interferometry, as a full-field,
      non-contact, and highly sensitive optical measurement technique, has been
      applied, where the evolving field is represented as dynamic phase distribution. A
      dynamic phase retrieval algorithm, called least-squares with 3 unknowns (LS3U),
      which estimates the phase change between each two consecutive patterns by a least
      squares fitting method and denoises the phase change by a windowed Fourier
      filtering (WFF) algorithm, has been shown to be a simple yet effective algorithm.
      However, LS3U is computationally expensive, restricting its potential application
      in real-time dynamic phase retrieval systems. In this paper, a real-time LS3U
      algorithm powered by GPU parallel computing is proposed, with which frame rates
      of up to 64.5 frames per second (fps) and 131.8 fps are achieved on NVIDIA's GTX
      680 and GTX 1080 graphics cards, respectively.

PMID- 29047754
TI  - Scene reassembly after multimodal digitization and pipeline evaluation using
      photorealistic rendering.
AB  - Transparent objects require acquisition modalities that are very different from
      the ones used for objects with more diffuse reflectance properties. Digitizing a
      scene where objects must be acquired with different modalities requires scene
      reassembly after reconstruction of the object surfaces. This reassembly of a
      scene that was picked apart for scanning seems unexplored. We contribute with a
      multimodal digitization pipeline for scenes that require this step of reassembly.
      Our pipeline includes measurement of bidirectional reflectance distribution
      functions and high dynamic range imaging of the lighting environment. This
      enables pixelwise comparison of photographs of the real scene with renderings of
      the digital version of the scene. Such quantitative evaluation is useful for
      verifying acquired material appearance and reconstructed surface geometry, which
      is an important aspect of digital content creation. It is also useful for
      identifying and improving issues in the different steps of the pipeline. In this
      work, we use it to improve reconstruction, apply analysis by synthesis to
      estimate optical properties, and to develop our method for scene reassembly.

PMID- 29047755
TI  - Common-mode noise reduction in an atomic spin gyroscope using optical
      differential detection.
AB  - Optical rotation of linearly polarized light is used to measure atom spin
      precession in an atomic spin gyroscope (ASG). However, the common-mode noise in
      the polarization measurement seriously affects the performance of the sensitive
      ASG. Here we propose an optical differential detection method based on the
      photoelastic polarization modulation, which could effectively eliminate the light
      power fluctuation of the laser source and optical elements, while removing the
      polarization noise and the residual birefringence. The feasibility and efficiency
      of this method have been verified experimentally. The rotation sensitivity of the
      ASG is an order of magnitude better, and the long-time stability is significantly
      improved. In addition, this method is easier to implement because noise sources
      do not need to be strictly distinguished.

PMID- 29047756
TI  - Polarimetric target depth sensing in ambient illumination based on polarization
      coded structured light.
AB  - Depth sensing is a basic issue in three-dimensional computer vision, and
      structured light is one of the most prevailing methods for it. However, complex
      surroundings and strong ambient illumination are fairly unfavorable to depth
      sensing based on structured light. Complex surroundings increase computation
      overhead and require extra effort to be separated from the target object. Strong
      ambient illumination is unfavorable to the signal-noise ratio of structured light
      and, thus, increases the difficulty of decoding. In this paper, we propose that
      the polarization-coded structured light is capable of target enhanced depth
      sensing in ambient illumination. We present the polarimetric principle, an
      improved algorithm of polarization-coded structured light, and signal-noise-ratio
      analysis in ambient illumination. Experimental results show that polarization
      coded structured light is efficient and robust for target depth sensing of a
      complicated environment. The polarization-coded structured light is promising to
      the target depth sensing in an outdoor scenario and industrial inspection.

PMID- 29047758
TI  - Interferometric inverse synthetic aperture ladar target detection method.
AB  - To improve the target detection performance of inverse synthetic aperture ladar
      (ISAL) under the situation that there is Doppler bandwidth ambiguity, we consider
      energy accumulation of echo signals along a range through matched illumination.
      However, since the target impulse responses change with the target aspect angle,
      the phase shifts along slow-time between range cells are different, and the
      output of matched illumination fluctuates along slow-time. To reduce the slow
      time fluctuation of matched illumination under additive white Gaussian noise
      assumption, we have proposed an interferometric ISAL (InISAL) target detection
      method based on interferometry processing and principal component analysis (PCA)
      in this paper. After the interferometry processing, the interferometric phase
      shifts along slow-time of all range cells are approximately the same. Then PCA is
      introduced to reduce the impact of noise, interference, and cross-terms of
      interferometry processing. Thus, the slow-time fluctuation of matched
      illumination can be decreased, and the target detection performance is improved.
      The proposed method has been validated with both simulated data of InISAL and
      real data of millimeter-wave interferometric synthetic aperture radar.

PMID- 29047757
TI  - Investigation on the effect of output mirror transmission in WS2-based red-light
      passively Q-switched Pr:ZBLAN all-fiber lasers.
AB  - We report the experimental investigation of visible passively Q-switched Pr3+
      doped all-fiber lasers with tungsten disulfide (WS2) saturable absorber, where
      red-light short-pulse generations from different output mirror transmissions are
      systemically characterized. The proposed simple and compact all-fiber linear
      cavity was constructed by a fiber-pigtail-based blue laser-diode pump, a Pr3+
      doped fluorozirconate glass active fiber, and the fiber end-facet mirrors.
      Integrating a free-standing layered WS2 film into the laser cavity initiated the
      Q-switching operation. Stable microsecond-duration output pulses with kilohertz
      repetition rates are achieved, corresponding to a few mW/nJ average output power
      and single-pulse energy. The comparisons on red-light Q-switched output
      parameters for output transmissions of both ~40% and ~80% are performed. This
      work could provide a useful guideline to manipulate the output performance of
      visible pulsed all-fiber lasers for various practical applications.

PMID- 29047759
TI  - Multiple-wavelength range-gated active imaging in superimposed style for moving
      object tracking.
AB  - Having laid down previously the foundations of the multiple-wavelength range
      gated active imaging (WRAI) principle in flash mode and accumulation mode, its
      use in superimposed style for the direct tracking of moving objects was studied.
      The movement is supposed to be in a transverse plane of the scene. Each emitted
      laser pulse with a different wavelength visualizes the object at a specific time.
      Therefore, the wavelength set allows us to freeze the different positions of the
      object in the recorded image according to the laser emission period. Thus, in
      each recorded image, the object trajectory can be visualized directly according
      to these specific moments, allowing us to deduce the speed and the acceleration
      of the object at the same time. Another advantage, especially when the object
      trajectory is unpredictable, is that the wavelength progression indicates the
      trajectory direction. The principle being independent of the video frequency, the
      object speed can be very high. Furthermore, the range gating allows improvement
      of the object visibility through scattering environments. Three cases were
      identified and studied in superimposed style. Although the first case has not
      been used with range gating, it allowed us to show the possibility of using a
      traditional color camera. On the other hand, the two cases applying range gating
      required management of the exposure time. In each case, the temporal behavior was
      studied, as well as the possible speeds according to the object distance. The
      experimental test results validated the theoretical part and the possibility to
      determine the trajectory and the speed of a moving object with the WRAI principle
      in superimposed style.

PMID- 29047760
TI  - Electrical and optical properties of reduced graphene oxide thin film deposited
      onto polyethylene terephthalate by spin coating technique.
AB  - We present the reduction of solution processed graphene oxide films by hydrogen
      iodide vapor. The films were studied by Raman spectroscopy and Fourier-transform
      infrared spectroscopy and its optoelectronic properties characterized. We
      obtained reduced graphene oxide films on polyethylene terephthalate flexible
      substrates with good electrical properties, 3.74*10-6  Omega.m, and high optical
      transmittance of 70% in the visible range. The fabricated layers contain graphene
      sheets with sizes up to ~10  MUm long and ~6  MUm wide. The presented solution,
      with highly concentrated processed graphene oxide, could be used as printing ink
      for manufacturing transparent and conductive electrodes on plastic substrates
      without the requirement of elevated temperatures.

PMID- 29047761
TI  - Spectrally controlled interferometry.
AB  - Optical interferometers are typically categorized by their source type into
      incoherent (white-light) and coherent (laser). Both approaches provide adequate
      solutions for many measurement applications, offer unique advantages, and suffer
      distinct limitations. A novel interferometry method, spectrally controlled
      interferometry, is presented, which successfully merges many advantages from both
      categories while bypassing some of the limitations. The relationship between
      measurement accuracy and fringe stability as a function of fundamental control
      parameters is explored. Surface measurements of common optical components are
      presented, and method specific noise sources and measurement accuracy are
      assessed as well.

PMID- 29047762
TI  - Analysis of charcoal blast furnace slags by laser-induced breakdown spectroscopy.
AB  - Laser-induced breakdown spectroscopy (LIBS) was used for the analysis of charcoal
      blast furnace slags. Plasma was generated by an application of a 1064 nm
      wavelength Nd:YAG laser beam to the surface of pellets created from the slags.
      The presence of Al, Ca, Fe, K, Mg, Mn, and Si was determined by identifying their
      characteristic spectral signatures. Multivariate analysis was performed for the
      quantification of these elements. The predicted LIBS results were found in
      agreement with the inductively coupled plasma optical emission spectrometry
      analysis. The limit of detection for Al, Ca, Fe, K, Mg, Mn, and Si was calculated
      to be 0.10%, 0.22%, 0.02%, 0.01%, 0.01%, 0.005%, and 0.18%, respectively.

PMID- 29047763
TI  - Passive ranging using a filter-based non-imaging method based on oxygen
      absorption.
AB  - To solve the problem of poor real-time measurement caused by a hyperspectral
      imaging system and to simplify the design in passive ranging technology based on
      oxygen absorption spectrum, a filter-based non-imaging ranging method is
      proposed. In this method, three bandpass filters are used to obtain the source
      radiation intensities that are located in the oxygen absorption band near 762 nm
      and the band's left and right non-absorption shoulders, and a photomultiplier
      tube is used as the non-imaging sensor of the passive ranging system. Range is
      estimated by comparing the calculated values of band-average transmission due to
      oxygen absorption, tauO2 , against the predicted curve of tauO2 versus range. The
      method is tested under short-range conditions. Accuracy of 6.5% is achieved with
      the designed experimental ranging system at the range of 400 m.

PMID- 29047764
TI  - Surface topography measurement by frequency sweeping digital holography.
AB  - High-precision measurements of mechanical parts' surface topography represent an
      essential task in many industry sectors. Examples of such tasks are, e.g.,
      precise alignments of opto-mechanical systems, large object deformation
      measurements, evaluation of object shape, and many others. Today, the standard
      method used for such measurements is based on use of coordinate measuring
      machines (CMMs). Unfortunately, CMMs have severe shortcomings: low measurement
      point density, long measurement time, risk of surface damage, etc. Indeed, the
      measurement time rapidly increases with the object complexity and with the
      density of measurement points. In this paper, we have developed a method for
      surface topography measurements called "frequency sweeping digital holography"
      (FSDH). Our developed FSDH method is based on the principles of wavelength
      scanning interferometry. It allows surface topography measurements of objects
      with a diameter of several hundred of mms and a high axial accuracy reaching 10
      MUm. The greatest advantage of the presented FSDH is the fact that the surface
      topology data are captured in a motionless manner by means of a relatively simple
      setup. This makes the FSDH method a suitable technique for topography
      measurements of objects with complex geometries made of common materials (such as
      metals, plastics, etc.), as well as for the characterization of complex composite
      structures such as acoustic metamaterials, active acoustic metasurfaces, etc.
      Measurement method principles, setup details, lateral resolution, and axial
      accuracy are discussed.

PMID- 29047765
TI  - Off-surface optic axis birefringent filters for smooth tuning of broadband
      lasers.
AB  - Transition metal-doped gain media, such as Ce:LiCAF, Ti:sapphire, Cr:ZnSe, and
      Fe:ZnSe, possess wide gain bandwidths that could provide ultra broadly tunable
      laser output with the usage of adequate intracavity tuning elements. Birefringent
      filters (BRFs) are a low-cost and easy to use solution for tuning. However, for
      ultrabroad gain media, regular on-surface optic axis BRFs could not provide
      smooth tuning of laser wavelength in the whole emission range. Basically, regular
      BRFs could not accommodate a large enough free spectral range with acceptable
      modulation depth variation while tuning, due to their slow tuning rates.
      Motivated by this, in this study, we have numerically investigated the effect of
      optic axis orientation on filter parameters for magnesium fluoride birefringent
      tuning plates. We have shown that a magnesium fluoride BRF with an optic axis
      diving by 30 degrees  into the plate could provide smooth tuning of ultra-broad
      laser gain media. A similar analysis has shown that for broadband tuning
      applications, the optimum optic axis diving angle lies around 25 degrees  for
      crystal quartz BRFs. The proposed filters have the potential to be useful in
      tuning of broadband lasers in continuous-wave, long-pulsed, and femtosecond
      operation regimes.

PMID- 29047766
TI  - Measurement of refractive index profiles in optical waveguides by moire
      deflectometry technique.
AB  - Measurement of refractive index profiles in optical waveguides is an important
      issue for controlling manufacturing procedures and determination of some
      important characteristics of waveguides. In this paper, an optical waveguide is
      considered as a phase object. When collimated laser beams are illuminated on
      waveguides, the refractive index gradient distorts the plane waves, then the
      distortion is determined by use of the moire deflectometry method. Dimensions of
      the waveguides under study are on the order of 10 MUm, so the moire deflectometry
      setup was changed and optimized for measuring in the micrometer dimensions. This
      modified and generalized moire deflectometry technique helps to intensify plane
      wave distortion thousands of times and expands it to be measurable. Finally, by
      analysis of moire fringes, we succeeded in determining the refractive index
      profile of an optical waveguide by approximation of semi-cylindrical symmetry.

PMID- 29047767
TI  - Reflectance calculations of anisotropic dielectric constants of graphene-like two
      dimensional materials.
AB  - A new optical method for determining anisotropic dielectric constants of graphene
      like two-dimensional materials on semiconductor or metal substrates is developed.
      The method is based on the surface differential reflectance measurements at three
      different incident angles. The inversion problem is resolved analytically in a
      long-wavelength approximation, where graphene is discussed within the framework
      of macroscopic electrodynamics as a uniaxially anisotropic film with the optical
      axis perpendicular to the film surface. The method is fast and has no need for
      the initial guesses of the desired parameters. It also offers an effective
      technique to get good start points for iterative numerical methods to improve the
      preliminary results. The method is unique in its simplicity and, therefore,
      important for graphene research.

PMID- 29047768
TI  - On-chip membrane-based GaInAs/InP waveguide-type p-i-n photodiode fabricated on
      silicon substrate.
AB  - Toward the realization of ultralow-power-consumption on-chip optical
      interconnection, two types of membrane-based GaInAs/InP p-i-n photodiodes were
      fabricated on Si host substrates by using benzocyclobutene bonding. A
      responsivity of 0.95 A/W was estimated with a conventional waveguide-type
      photodiode with an ~30-MUm-long absorption region. The fitting curves based on
      the experimental data indicated that an absorption efficiency above 90% could be
      achieved with a length of 10 MUm. In addition, increased absorption per length of
      a photonic crystal waveguide-type photodiode was obtained because of the enhanced
      lateral optical confinement or the slow-light effect, enabling a further
      reduction in the device length.

PMID- 29047769
TI  - Performance of photomultipliers in the context of laser-induced incandescence.
AB  - Photomultiplier tubes (PMTs) are widely used as detectors for laser-induced
      incandescence (LII), a diagnostics method for gas-borne particles that requires
      signal detection over a large dynamic range with nanosecond time resolution
      around the signal peak. Especially when more than one PMT is used (i.e., for
      pyrometric temperature measurements) even small deviations from the linear
      detector response can lead to significant errors. Reasons for non-linearity
      observed in other PMT measurement techniques are summarized and strategies to
      identify non-linear PMT operation in LII are outlined. To quantify the influence
      of the non-linear behavior, experiments at similar light levels as those
      encountered in LII measurements are carried out, and errors propagated in two
      color pyrometry-derived temperatures are determined. As light sources, a
      calibrated broadband light source and light-emitting diodes (LEDs), centered at
      the bandpass filter wavelengths of the LII detectors, were used. The LEDs were
      operated in continuous and pulsed (<300  ns) mode, respectively, to simulate DC
      background radiation (e.g., from sooting flames) and similar pulsed signal traces
      as in typical LII measurements. A measured linearity deviation of up to 10% could
      bias the temperature determination by several hundred Kelvin. Guidelines are
      given for the design and the operation of LII setups, which allow users to
      identify and prevent errors.

PMID- 29047770
TI  - Three-dimensional image acquisition and reconstruction system on a mobile device
      based on computer-generated integral imaging.
AB  - A mobile three-dimensional image acquisition and reconstruction system using a
      computer-generated integral imaging technique is proposed. A depth camera
      connected to the mobile device acquires the color and depth data of a real object
      simultaneously, and an elemental image array is generated based on the original
      three-dimensional information for the object, with lens array specifications
      input into the mobile device. The three-dimensional visualization of the real
      object is reconstructed on the mobile display through optical or digital
      reconstruction methods. The proposed system is implemented successfully and the
      experimental results certify that the system is an effective and interesting
      method of displaying real three-dimensional content on a mobile device.

PMID- 29047771
TI  - Astigmatism-corrected echelle spectrometer using an off-the-shelf cylindrical
      lens.
AB  - As a special kind of spectrometer with the Czerny-Turner structure, the echelle
      spectrometer features two-dimensional dispersion, which leads to a complex
      astigmatic condition. In this work, we propose an optical design of astigmatism
      corrected echelle spectrometer using an off-the-shelf cylindrical lens. The
      mathematical model considering astigmatism introduced by the off-axis mirrors,
      the echelle grating, and the prism is established. Our solution features
      simplified calculation and low-cost construction, which is capable of overall
      compensation of the astigmatism in a wide spectral range (200-600 nm). An optical
      simulation utilizing ZEMAX software, astigmatism assessment based on Zernike
      polynomials, and an instrument experiment is implemented to validate the effect
      of astigmatism correction. The results demonstrated that astigmatism of the
      echelle spectrometer was corrected to a large extent, and high spectral
      resolution better than 0.1 nm was achieved.

PMID- 29047772
TI  - Pseudo-random masks for angular alignment.
AB  - We present an alignment technique that exploits angular correlations by employing
      a pair of masks, which encode in an angular format pseudo-random sequences. The
      angular correlator generates peaked irradiance distributions on-axis, provided
      that the elements of the pair are aligned. Otherwise, the on-axis irradiance
      distribution decreases to a minimum value. Since the proposed angular correlator
      is independent of the lateral magnification, it is useful for testing the
      performance of varifocal lenses. A merit function describes the tolerance to
      focus errors associated with the location of a small size detector. We use
      linearly polarized films for showing that the technique also works well with
      broad band light.

PMID- 29047773
TI  - Transient dynamic distributed strain sensing using photonic crystal waveguides.
AB  - This paper presents a new type of one-dimensional photonic crystal (PC) waveguide
      sensor and a technique for prediction of transient strain response accurately.
      The PC waveguide is integrated on a silicon substrate. We investigate the effect
      of non-uniform strain localization on the optical signal and use that information
      to capture the transient strain. Wavelength shift due to distributed strain field
      is modeled by incorporating the mechanically deformed geometry and photo-acoustic
      coupling through Pockels effect in a finite element formulation. We demonstrate
      the advantages of using our proposed method, where multiple spectral peak shift
      is used instead of single peak shift in order to improve sensing output accuracy
      and also to estimate the sensor parameter regressively, where the signal's
      bandwidth is limited. The maximum sensitivity of the waveguide sensor in terms of
      wavelength shift is estimated to be 0.36 pm/MUstrain in single-peak-based
      sensing, whereas the proposed adaptive multispectral estimation scheme shows an
      enhanced sensitivity of 4.029 pm/MUstrain.

PMID- 29047774
TI  - Feasibility study of high spatial resolution multimodality fluorescence
      tomography in ex vivo biological tissue.
AB  - Previously, we demonstrated that temperature-modulated fluorescence tomography
      (TM-FT) could provide fluorescence images with high quantitative accuracy and the
      spatial resolution of focused ultrasound. TM-FT is based on scanning the focused
      ultrasound across the medium to activate temperature-reversible fluorescent
      nanoprobes (ThermoDots). This technique can resolve small fluorescent targets
      located several centimeters deep in turbid media with millimeter resolution. Our
      past studies with this multimodality technique used agar phantoms, which could
      not represent the true heterogeneous nature of the acoustic and optical
      properties of biological tissue. In this work, we report the results of the first
      TM-FT study performed on ex vivo chicken breast tissue. In order to improve the
      spatial resolution of this technique, diffuse optical tomography is also used to
      better estimate the optical property maps of the tissue, which is utilized as
      functional a priori for the TM-FT reconstruction algorithm. These ex vivo results
      show that TM-FT can accurately recover the concentration and position of a 1.5 
      mm*5  mm inclusion filled with ThermoDots. Since the inclusion is embedded 2 cm
      deep in the chicken breast sample, these results demonstrate the great potential
      of TM-FT for future in vivo small animal imaging.

PMID- 29047775
TI  - Selective photo-oxidation induced bi-periodic plasmonic structures for high
      density data storage.
AB  - Stable and controllable optical memory is necessary for the development of
      current information technology. In this context, Ag/TiO2 films have received much
      attention for their photosensitivity in wavelength and polarization, which can be
      applied to high-density optical storage. Here, we carried out dual-wavelength
      holographic recording using 403.4 nm and 532 nm lasers, and obtained mixed
      microfringes based on selective photodissolution of Ag nanoparticles of various
      sizes in TiO2 nanoporous films. Two recording methods of simultaneous and
      sequential multiplexing were investigated. It was found that using simultaneous
      irradiation it is easier to obtain equivalent efficiency in both spectral hole
      burning and multiplexed grating diffraction, compared with the sequential one.
      The results can be explained by the Time-accumulation effect during Ag+ ion
      diffusion and migration in holographic recordings. Based on such properties,
      multiplexed-holographic fringes with uniform contrast were reserved by
      simultaneous recording in Ag/TiO2 films. This work provides a new strategy for
      fabrication of photonic devices with complex microstructures.

PMID- 29047776
TI  - Measuring optical constants of ultrathin layers using surface-plasmon-resonance
      based imaging ellipsometry.
AB  - A setup for surface-plasmon-resonance- (SPR) based imaging ellipsometry was
      developed, which gains from the sensitivities of both SPR and ellipsometry to
      ultrathin film parameters. It is based on Otto's configuration for prism-sample
      coupling and a wide-beam imaging ellipsometry. A set of ultrathin gold and silver
      films was measured to determine their optical constants and thicknesses. Coupling
      the sample using a prism with a convex surface enables us to capture images of
      generated SPR elliptical fringes, which correspond to different SPR amplitude
      values at different air gap thicknesses. Analysis of the images acquired at
      different polarizer and analyzer angles provides the ellipsometric functions Psi
      and Delta versus thickness of air gap and hence the extraction of the optical
      constants of ultrathin metal films. The measured film thickness is in agreement
      with the results of x-ray reflectivity measurements.

PMID- 29047777
TI  - Stereo line-scan sensor calibration for 3D shape measurement.
AB  - The stereo line-scan sensor opens up new potentialities for 3D measurement owing
      to the ultra-high resolution and acquisition rate. Calibration is a crucial key
      technology for a stereo line-scan sensor. This paper presents a precise
      calibration method for the stereo line-scan sensor. Several reference points are
      installed onto the sensor's body as an intermediary. The calibration turns into a
      two-step process: calibrating the cameras in the laboratory prior to measurement
      and locating the sensor in an actual measurement field. A mobile apparatus that
      comprises a planar pattern and extra reference points is designed. By
      incorporating the apparatus in combination with an auxiliary instrument, an
      optimal calibration configuration is created by placing the apparatus into
      multiple positions. A robust algorithm is proposed to enhance the stability of
      the parameter estimation. The quality of the calibration method is experimentally
      tested, and the performance is further investigated. Experimental results
      demonstrate that the proposed method offers a practical solution to calibrate a
      stereo line-scan sensor for 3D shape measurement.

PMID- 29047778
TI  - Low-cost dynamic real-time foveated imager.
AB  - Foveated imaging systems have the ability to capture local high-resolution or
      high-magnification images with wide field of view (FOV); thus, they have great
      potential for applications in the field of monitoring and remote sensing of
      unmanned aerial vehicles. Hence, foveated optical systems are in strong demand.
      However, the existing foveated imaging systems either are equipped with expensive
      modulators or require fixing the local high resolution imaging field, which is
      not suitable for mass production or object tracking in industrial applications.
      We propose a low-cost dynamic real-time foveated imaging system for extensive use
      in the listed applications. Specifically, we place a microlens behind the first
      intermediary image plane to modulate the local focal length, constructing a local
      high magnification imaging channel. One two-axis translation stage drives the
      microlens to scan in the plane perpendicular to the optical axis, resulting in
      dynamic local high magnifying imaging. Furthermore, the peripheral imaging
      channel and the foveated imaging channel focus on the same detector, and the post
      image fusion is unnecessary; the system consists of only a common aspherical lens
      and thus is very inexpensive. The experimental system has a focal length of 25
      mm, a full FOV of 30 degrees , and an entrance pupil diameter of 5 mm, while the
      local high magnifying imaging channel has a focal length of 35 mm and FOV of 15
      degrees . Experiment results show that the low-cost dynamic real-time foveated
      imaging system performs very well.

PMID- 29047779
TI  - Thermally stable multi-color phosphor-in-glass bonded on flip-chip UV-LEDs for
      chromaticity-tunable WLEDs.
AB  - In this paper, we propose a thermally stable multi-color phosphor-in-glass (PiG)
      for chromaticity-tunable white light-emitting diodes (WLEDs). The multi-color PiG
      has a red, green, and blue (RGB) phosphor glass layer, which was screen-printed
      and co-sintered on a glass plate with a low temperature of 600 degrees C. The
      WLED with ultra-compact structure was fabricated by the RGB-PiG directly bonded
      on a flip-chip ultraviolet (UV) LED. By controlling the weight ratio of R?G?B
      phosphors, the thickness of the RGB layer, and the weight ratio of phosphors to
      glass powders (PtG), the chromaticity of RGB-PiG based WLEDs can be effectively
      tuned with high color quality. With the R?G?B ratio of 2?3?2, the RGB thickness
      of 75 MUm, and the PtG ratio of 2?1, the RGB-PiG based WLED achieves a natural
      white light with a luminous efficacy (LE) of 27.8 lm/W, a correlated color
      temperature of 4245 K, and a color rendering index of 92.6 at the current of 350
      mA. The LE losses of the RGB-PiG based and RGB phosphor-in-silicone based WLEDs
      are 4.7% and 14.6% after the aging tests of 1000 h at 100 degrees C,
      respectively. The results demonstrate that the multi-color PiG is a promising
      converter for UV-excited WLEDs.

PMID- 29047780
TI  - Variations in the water vapor distribution and the associated effects on fog and
      haze events over Xi'an based on Raman lidar data and back trajectories.
AB  - A combination of more than two years of water vapor lidar data with back
      trajectory analysis using the hybrid single-particle Lagrangian integrated
      trajectory (HYSPLIT) model was used to study the long-range transport of air
      masses and the water vapor distribution characteristics and variations over
      Xi'an, China (34.233 degrees  N, 108.911 degrees  E), which is a typical city in
      Northwest China. High-quality profiles of the water vapor density were derived
      from a multifunction Raman lidar system built in Xi'an, and more than 2000 sets
      of profiles with >400 nighttime observations from October 2013 to July 2016 were
      collected and used for statistical and quantitative analyses. The vertical
      variations in the water vapor content were discussed. A mutation height of the
      water vapor exists at 2-4 km with a high occurrence rate of ~60% during the
      autumn and winter seasons. This height reflects a distinct stratification in the
      water vapor content. Additionally, the atmospheric water vapor content was mainly
      concentrated in the lower troposphere, and the proportion of the water vapor
      content at 0.5-5 km accounted for 80%-90% of the total water vapor below 10 km.
      Obvious seasonal variations were observed, including large water vapor content
      during the spring and summer and small content during the autumn and winter.
      Combined with back trajectory analysis, the results showed that markedly
      different water vapor transport pathways contribute to seasonal variations in the
      water vapor content. South and southeast airflows dominated during the summer,
      with 30% of the 84 trajectories originating from these areas; however, the air
      masses during the winter originated from the north and local regions (64.3%) and
      from the northwest (27%). In addition, we discussed variations in the water vapor
      during fog and haze weather conditions during the winter. A considerable
      enhancement in the mean water vapor density at 0.5-3 km exhibited a clear
      positive correlation (correlation coefficient >0.8) with the PM2.5 and PM10
      concentrations. The results indicate that local airflow trajectories mainly
      affect water vapor transport below the boundary layer, and that these flows are
      closely related to the formation of fog and haze events in the Xi'an area.

PMID- 29047781
TI  - Experimental demonstration of 12.5  GHz wideband chaos in symmetric dual-port
      EDFRL.
AB  - We study the dynamics of chaos in a dual-port erbium-doped fiber ring laser
      (EDFRL). The laser consists of two erbium-doped fibers, intracavity filters at
      1549.32 nm, isolators, and couplers. At both ports, the laser transitions into
      the chaotic regime for pump currents greater than 100 mA via the period doubling
      route. We calculate the largest Lyapunov exponent using Rosenstein's algorithm.
      We obtain positive values for the largest Lyapunov exponent (~0.2) for embedding
      dimensions 5, 7, 9, and 11 indicating chaos. We compute the power spectral
      density of the photocurrents at the output ports of the laser. We observe a
      bandwidth of 12.5 GHz at both ports. This ultra-wideband nature of chaos obtained
      has potential applications in high-speed random number generation and
      communication.

PMID- 29047782
TI  - Utilizing electromagnetically induced transparency in InAs quantum dots for all
      optical transistor design.
AB  - We propose a multilayer medium with semiconductor quantum dot nano-structures as
      a defect layer for all-optical control of the 1.55 MUm probe beam. The effect of
      the coupling field and incoherent pump on absorption and dispersion properties of
      the quantum dot defect layer is investigated. Depending on the intensity of the
      coupling field and rate of the incoherent pump field, the possibility of the
      absorption cancellation and even amplification are demonstrated. The optimum
      values of the coupling field intensity and incoherent pump field for complete
      transmission or amplification are obtained. The dynamical behavior of the
      structure is investigated, and the estimated switching time scales are about tens
      of picoseconds.

PMID- 29047783
TI  - Development and accuracy of a multipoint method for measuring visibility.
AB  - Accurate measurements of visibility are of great importance in many fields. This
      paper reports a multipoint visibility measurement (MVM) method to measure and
      calculate the atmospheric transmittance, extinction coefficient, and
      meteorological optical range (MOR). The relative errors of atmospheric
      transmittance and MOR measured by the MVM method and traditional transmissometer
      method are analyzed and compared. Experiments were conducted indoors, and the
      data were simultaneously processed. The results revealed that the MVM can
      effectively improve the accuracy under different visibility conditions. The
      greatest improvement of accuracy was 27%. The MVM can be used to calibrate and
      evaluate visibility meters.

PMID- 29047784
TI  - Signal detection algorithms for interferometric sensors with harmonic phase
      modulation: distortion analysis and suppression.
AB  - In the current paper, distortions in digital demodulation schemes with harmonic
      phase modulation for interferometric optical sensors are considered. In
      particular, the influence of target signal variations on phase demodulation
      errors is theoretically evaluated. An analytical expression describing the phase
      error magnitude dependence on the first derivative and mean value of the measured
      signal and amplitude of the phase modulation in the case of a simple 4-point
      demodulation algorithm is derived. After that, an approach for synthesizing
      algorithms with suppressed sensitivity to target signal variations is developed.
      Based on this approach, a novel 4+1 demodulation algorithm is proposed. It is
      shown analytically that the demodulation error of the new 4+1 algorithm is
      proportional to the second derivative of the target signal, and therefore, is
      typically several orders of magnitude smaller than in the case of the 4-point
      algorithm. The correspondence between analytical expressions and real phase
      errors induced by target signal variations is verified by means of numeric
      simulation.

PMID- 29047785
TI  - Image decomposition fusion method based on sparse representation and neural
      network.
AB  - For noisy images, in most existing sparse representation-based models, fusion and
      denoising proceed simultaneously using the coefficients of a universal
      dictionary. This paper proposes an image fusion method based on a cartoon +
      texture dictionary pair combined with a deep neural network combination (DNNC).
      In our model, denoising and fusion are carried out alternately. The proposed
      method is divided into three main steps: denoising + fusion + network denoising.
      More specifically, (1) denoise the source images using external/internal methods
      separately; (2) fuse these preliminary denoised results with external/internal
      cartoon and texture dictionary pair to obtain the external cartoon + texture
      sparse representation result (E-CTSR) and internal cartoon + texture sparse
      representation result (I-CTSR); and (3) combine E-CTSR and I-CTSR using DNNC (EI
      CTSR) to obtain the final result. Experimental results demonstrate that EI-CTSR
      outperforms not only the stand-alone E-CTSR and I-CTSR methods but also state-of
      the-art methods such as sparse representation (SR) and adaptive sparse
      representation (ASR) for isomorphic images, and E-CTSR outperforms SR and ASR for
      heterogeneous multi-mode images.

PMID- 29047786
TI  - Integrated reconfigurable photonic filters based on interferometric fractional
      Hilbert transforms.
AB  - In this paper, we present integrated reconfigurable photonic filters using
      fractional Hilbert transformers (FrHTs) and optical phase tuning structure within
      the silica-on-silicon platform. The proposed structure, including grating-based
      FrHTs, an X-coupler, and a pair of thermal tuning filaments, is fabricated
      through the direct UV grating writing technique. The thermal tuning effect is
      realized by the controllable microheaters located on the two arms of the X
      coupler. We investigate the 200 GHz maximum bandwidth photonic FrHTs based on
      apodized planar Bragg gratings, and analyze the reflection spectrum responses.
      Through device integration and thermal modulation, the device could operate as
      photonic notch filters with 5 GHz linewidth and controllable single sideband
      suppression filters with measured 12 dB suppression ratio. A 50 GHz instantaneous
      frequency measuring system using this device is also schematically proposed and
      analyzed with potential 3 dB measurement improvement. The device could be
      configured with these multiple functions according to need. The reconfigurable
      structure has great potential in ultrafast all-optical signal processing fields.

PMID- 29047787
TI  - Dual-sensitivity profilometry with defocused projection of binary fringes.
AB  - A dual-sensitivity profilometry technique based on defocused projection of binary
      fringes is presented. Here, two sets of fringe patterns with a sinusoidal profile
      are produced by applying the same analog low-pass filter (projector defocusing)
      to binary fringes with a high- and low-frequency spatial carrier. The high
      frequency fringes have a binary square-wave profile, while the low-frequency
      binary fringes are produced with error-diffusion dithering. The binary nature of
      the binary fringes removes the need for calibration of the projector's nonlinear
      gamma. Working with high-frequency carrier fringes, we obtain a high-quality
      wrapped phase. On the other hand, working with low-frequency carrier fringes we
      found a lower-quality, nonwrapped phase map. The nonwrapped estimation is used as
      stepping stone for dual-sensitivity temporal phase unwrapping, extending the
      applicability of the technique to discontinuous (piecewise continuous) surfaces.
      We are proposing a single defocusing level for faster high- and low-frequency
      fringe data acquisition. The proposed technique is validated with experimental
      results.

PMID- 29047788
TI  - Analysis on multifocal contact lens design based on optical power distribution
      with NURBS.
AB  - This paper aims to develop and analyze the design method of multifocal contact
      lenses to obtain curvature continuity in the optical surfaces with the high
      addition (Add) powers by adjusting non-uniform rational B-spline (NURBS) curves.
      The paper has developed mathematical formulae to generate the optical power
      distributions in which the powers continuously change from either near or distant
      center to the opposite focal length in the periphery of the optical region with
      different change rates and Add power values. This developed method can
      efficiently adjust and optimize three parameters, including control points,
      weight, and knots of the NURBS, to be anterior optical lens surface profiles to
      adapt for these given power profiles. The result shows that the proposed contact
      lenses not only achieve smooth and continuous anterior optical surfaces, but also
      satisfy various optical power distributions with high Add power values for
      different pupil diameters. Then, these designs of contact lenses can be feasibly
      converted to the computer-aided design format for analysis and manufacture for
      molding or single-point diamond turning. Experimental results of this method have
      been tested and proven when both the power distributions of simulation of lenses
      and the actual machined samples match the original specified powers provided by
      clinical demands of a multifocal contact lens. Future integration with variant
      clinical demands and optimization rules of lens design can be explored for a
      progressive contact lens.

PMID- 29047789
TI  - Geometrical optical transfer function: is it worth calculating?
AB  - In this paper, we explore the merit of calculating the geometrical optical
      transfer function (GOTF) in optical design by comparing the time to calculate it
      with the time to calculate the diffraction optical transfer function (DOTF). We
      determine the DOTF by numerical integration of the pupil function autocorrelation
      (that reduces to an integration of a complex exponential of the aberration
      difference function), 2D digital autocorrelation of the pupil function, and the
      Fourier transform (FT) of the point-spread function (PSF); and we determine the
      GOTF by the FT of the geometrical PSF (that reduces to an integration over the
      pupil plane of a complex exponential that is a scalar product of the spatial
      frequency and transverse ray aberration vectors) and the FT of the spot diagram.
      Our starting point for calculating the DOTF is the wave aberrations of the system
      in its pupil plane, and the transverse ray aberrations in the image plane for the
      GOTF. Numerical results for primary aberrations and some typical imaging systems
      show that the direct numerical integrations are slow, but the GOTF calculation by
      a FT of the spot diagram is two or even three times slower than the DOTF
      calculation by an FT of the PSF, depending on the aberration. We conclude that
      the calculation of GOTF is, at best, an approximation of the DOTF and only for
      large aberrations; GOTF does not offer any advantage in the optical design
      process, and hence negates its utility.

PMID- 29047790
TI  - Optical beam deflection sensor: design and experiments.
AB  - In this work, we present a double-pass optical beam deflection sensor and its
      optical design method. To accomplish that, a mathematical model was proposed and
      computational simulations were performed, in order to obtain the sensor's
      characteristic curves and to analyze its behavior as function of design
      parameters. The mathematical model was validated by comparison with the
      characteristic curves acquired experimentally. The sensor was employed to detect
      acoustic pulses generated by a pulsed laser in a sample surface, in order to show
      its potential for monitoring applications handling high energy input as laser
      welding or laser ablation.

PMID- 29047791
TI  - Optimal defocus selection based on normed Fourier transform for digital fringe
      pattern profilometry.
AB  - Owing to gamma-effect robustness and high-speed imaging capabilities, projector
      defocusing of binary-coded fringe patterns is by far the most widely used and
      effective technique in generating sinusoidal fringe patterns for three
      dimensional optical topography measurement with digital fringe projection
      techniques. However, this technique is not trouble-free. It is borne with
      uncertainty and challenges mainly because it remains somewhat difficult to
      quantify and ascertain the level of defocus required for desired fidelity in
      sinuousness of the projected fringe pattern. Too much or too little defocusing
      will affect the sinuosity accuracy of fringe patterns and consequently jeopardize
      the quality of the measurement results. In this paper, by combining intrinsic
      phase spectral sensitivities and normed Fourier transform, a method to quantify
      the amount of defocus and subsequently select the optimal degree of sinuosity for
      generating digital sinusoidal fringe patterns with projector defocusing for
      fringe pattern optical three-dimensional profilometry is proposed. Numerical
      simulations plus experiments give evidence of the feasibility and validity of the
      proposed method in enabling an improved digital binary defocusing technique for
      optical phase-shift profilometry using the digital fringe projection technique.

PMID- 29047792
TI  - Dispersion engineering of a microsphere via multi-layer coating.
AB  - Controlling dispersion of a whispering gallery mode resonator is of critical
      importance for many nonlinear applications, such as frequency comb generation,
      parametric oscillators, Raman lasers, stimulated Brillouin lasers, and ultrafast
      optics. Here, we show by numerical and theoretical modeling that dispersion can
      be strongly engineered in a three-layer-coated microsphere of high, low, and high
      refractive indices (RIs). We investigate the impact of the coating thickness, the
      gap between the two high-RI layers, the surrounding medium, and the coating
      materials on the group-velocity dispersion and discover that the dispersion is
      controllable over a broad range in both normal and anomalous dispersion regimes.
      Our approach provides dispersion engineering flexibility in any axisymmetric
      resonator with a three-layer-coating structure.

PMID- 29047793
TI  - Adaptive measurement method for miniature spectrometers used in cold
      environments.
AB  - Adaptive measurement is a major concern when using miniature spectrometers in
      extreme environments, especially when the ambient temperatures and incident light
      intensities vary greatly. In this study, parameters, including the signal output
      and the relevant noise and signal-to-noise ratio (SNR) of a fiber optic
      spectrometry system composed of a photodiode array miniature spectrometer and
      external driver electronics were examined at multiple integration times from -50
      degrees C to 30 degrees C, well below the specified operating temperature of this
      spectrometer. The relationships between those parameters and incident light level
      were also examined, at a single temperature of 0 degrees C. Based on these
      examinations, temperature-induced biases in the linear operating range of the
      spectrometer were identified. Signal output and the relevant noise and SNR in
      response to different integration times, temperatures, and incident light levels
      were assessed separately. These assessments were then used to develop an adaptive
      measurement method for estimating the incident light level and setting up an
      optimal integration time for this spectrometer, while autonomously adapting the
      variation in the ambient temperature and incident light level simultaneously.
      This approach provides a general framework for developing an adaptive measurement
      algorithm for miniature spectrometers, which face tremendous variations in
      ambient temperature and incident light level.

PMID- 29047794
TI  - Optical sensor system for time-resolved quantification of methane densities in
      CH4-fueled spark ignition engines.
AB  - We present the development and the first application of an optical sensor system
      that allows single-cycle determination of methane (CH4) concentration inside
      internal combustion (IC) engines. We use non-dispersive infrared absorption
      spectroscopy to detect the CH4 density with a time resolution up to 33 MUs at
      acquisition rates of 30 kHz. The measurement scheme takes advantage of the strong
      temperature dependence of the absorption band applying two detection channels for
      CH4 that detect different spectral regions of the nu3 anti-symmetric C-H-stretch
      absorption. The strategy allows the simultaneous determination of fuel
      concentration as well as gas temperature. We show the proof-of-concept by
      validation of the measurement strategy in static pressure cell experiments as
      well as its application to a methane-fueled IC engine using a modified spark plug
      probe. Our results clearly demonstrate that it is crucial to determine the CH4
      temperature in the probe volume. Due to thermal influences of the sensor probe,
      the temperature needed to calculate the desired quantities (fuel density, fuel
      concentration) significantly differs from the gas phase temperature in the rest
      of the combustion chamber and estimations from standard thermodynamic models,
      e.g., polytropic compression, will fail.

PMID- 29047795
TI  - Depth-of-field extension in integral imaging using multi-focus elemental images.
AB  - In integral imaging, one of the main challenges is the limited depth of field
      (DOF), which is mainly caused by the short focal length of the microlenses. In
      this paper, we propose a method to extend the DOF of a synthetic aperture
      integral imaging (SAII) system by realizing the image fusion method on the multi
      focus elemental images with different perspectives. In the proposed system, the
      contour-based object extraction method combined with size correction is developed
      to solve size inconsistency of the objects in the misaligned elemental images.
      The all-in-focus elemental images (EIs) combining selected features of multi
      focus elemental images are then obtained by the block-based image fusion method.
      In the last step, the reconstructed images with the extended DOF can be generated
      based on the all-in-focus EIs in the SAII system. Experimental results are
      presented to demonstrate the feasibility of the proposed system.

PMID- 29047796
TI  - Experimental and numerical study of underwater beam propagation in a Rayleigh
      Benard turbulence tank.
AB  - The propagation of a laser beam through Rayleigh-Benard (RB) turbulence is
      investigated experimentally and by way of numerical simulation. For the
      experimental part, a focused laser beam transversed a 5  m*0.5  m*0.5  m water
      filled tank lengthwise. The tank is heated from the bottom and cooled from the
      top to produce convective RB turbulence. The effect of the turbulence on the beam
      is recorded on the exit of the beam from the tank. From the centroid motion of
      the beam, the index of refraction structure constant Cn2 is determined. For the
      numerical efforts RB turbulence is simulated for a tank of the same geometry. The
      simulated temperature fields are converted to the index of refraction
      distributions, and Cn2 is extracted from the index of refraction structure
      functions, as well as from the simulated beam wander. To model the effect on beam
      propagation, the simulated index of refraction fields are converted to discrete
      index of refraction phase screens. These phase screens are then used in a split
      step beam propagation method to investigate the effect of the turbulence on a
      laser beam. The beam wander as well as the index of refraction structure
      parameter Cn2 determined from the experiment and simulation are compared and
      found to be in good agreement.

PMID- 29047797
TI  - Strain measurement at temperatures up to 800 degrees C using regenerated gratings
      produced in the highGe-doped and B/Ge co-doped fibers.
AB  - In this work, we have proposed a sensor for strain measurement in high
      temperature environments up to 800 degrees C by employing two regenerated fiber
      Bragg gratings. Two seed gratings (SGs) are inscribed in high Ge-doped and B/Ge
      codoped fibers, respectively, which possess different temperature sensitivities.
      To achieve two gratings with different strain sensitivities, one of the gratings
      is chemically etched to reduce the fiber diameter for strain sensitivity
      enhancement. A thermal annealing process is carried out to activate the grating
      regeneration in the SGs. The temperature and strain calibration experiments
      indicate that the proposed structure has uncertainty values of 23.42 MUepsilon
      and 5.83 degrees C over the ranges of 0-1000 MUepsilon and 20 degrees C-800
      degrees C, respectively.

PMID- 29047798
TI  - Inception learning super-resolution.
AB  - An efficient network for super-resolution, which we refer to as inception
      learning super-resolution (ILSR), is proposed. We adopt the inception module from
      GoogLeNet to exploit multiple features from low-resolution images, yet maintain
      fast training steps. The proposed ILSR network demonstrates low computation time
      and fast convergence during the training process. It is divided into three parts:
      feature extraction, mapping, and reconstruction. In feature extraction, we apply
      the inception module followed by dimensional reduction. Then, we map features
      using a simple convolutional layer. Finally, we reconstruct the high-resolution
      component using the inception module and a 1*1 convolutional layer. Experimental
      results demonstrate that the proposed network can construct sharp edges and clean
      textures, and reduce computation time by up to three orders of magnitude compared
      to state-of-the-art methods.

PMID- 29047799
TI  - Beam steering limitation of a Risley prism system due to total internal
      reflection.
AB  - Limitations of beam steering in Risley prisms, induced by total internal
      reflection, are investigated for the four typical configurations. The incident
      angles at the exit surfaces of double prisms are calculated by nonparaxial ray
      tracing and compared with the critical angle. On this basis, the limitations of
      the opening angle, relative orientation of the prisms, and ray deviation power of
      the system are derived. It is shown that the ray deviation power reaches its
      extreme value when the opening angles increase to a certain limit value for a
      given prism material. As the opening angles exceed the limit value, the prisms'
      relative orientation is limited. With the increase in refractive index, the limit
      value of opening angles decreases, while the extreme value of deviation power
      increases. In comparison to a 21-12, 12-12 configuration, a 21-21, 12-21
      configuration has a larger limit value of opening angles and also a larger
      extreme value (90 degrees ) of deviation power, so that it leaves a wider margin
      for the design of wide-angle beam steering system. The research can afford
      guidance for prism material and geometry choices in the design of a wide-angle
      Risley-prism-based beam steering system.

PMID- 29047800
TI  - Laser range finder approach based on a fieldable electro-optic dual optical
      frequency comb: a proof of concept.
AB  - In this paper a new laser range finder approach is presented. It is based on a
      fan of beams of different optical frequencies that are projected to the target.
      The detected back-reflected beams contain frequency-encoded information about its
      reflection angles, which are used for the calculation of the range by means of
      triangulation methods. The fan of beams is generated from a fieldable electro
      optic dual optical frequency comb generator and a diffractive optical system,
      without any moving parts. A proof-of-concept prototype of a range finder based on
      this approach was implemented and experimentally tested. An analysis of main
      sources of errors is also presented.

PMID- 29047801
TI  - Graph-regularized tensor robust principal component analysis for hyperspectral
      image denoising.
AB  - In this paper, we have developed a novel model that is named graph-regularized
      tensor robust principal component analysis (GTRPCA) for denoising hyperspectral
      images (HSIs). Incorporating spectral graph regularization into TRPCA makes the
      model more accurate by preserving local geometric structures embedded in a high
      dimensional space. Based on tensor singular value decomposition (t-SVD), we
      introduce a general tensor-based altering direction method of multipliers (ADMM)
      algorithm which can solve the proposed model for denoising HSIs. Experiments on
      both the synthetic and real captured datasets have demonstrated the effectiveness
      of the proposed method.

PMID- 29047802
TI  - Intermode beating mode-locking technique for a rare-earth-doped fiber pulsed
      laser.
AB  - In this paper, we report the intermode beating mode-locking of a 2  MUm Tm3+
      doped fiber laser (TDFL) pumped by a 1565 nm continuous-wave multi-longitudinal
      mode laser. Because strong intermode beating of the 1565 nm pump source induces
      the periodic modulation of 2 MUm intracavity power, stable mode-locking of the
      TDFL is successfully established by precisely matching the 2 MUm cavity frequency
      with the intermode-beating frequency of the 1565 nm pump source. The mode-locked
      laser, without requiring any specific mode-locking element, can stably emit the
      rectangular nanosecond pulses. The mode-locking operation at the center
      wavelength of 1980.35 nm has a >61  dB signal-to-noise ratio and a 34.496 MHz
      repetition rate. Although the preliminary results are not better than those of
      conventional mode-locking, intermode beating mode-locking in combination with
      rare-earth-doped fiber lasers could provide a promising and alternative solution
      for compact, low-cost, and high-performance pulsed laser sources.

PMID- 29047803
TI  - Light-efficient augmented reality 3D display using highly transparent retro
      reflective screen.
AB  - We propose and demonstrate a light-efficient 3D display using a highly
      transparent desktop-sized augmented reality screen. The display consists of a
      specially designed transparent retro-reflective screen and a pair of low-power
      pico-projectors positioned close to the viewer's eyes to provide stereo views.
      The transfer screen is an optically clear sheet partially patterned with retro
      reflective microspheres for high optical gain. The retro-reflective material
      buried in the screen reflects incident light back towards the projectors with a
      narrow scattering angle and facilitates the viewer to perceive a very bright
      content. The tabletop prototype mainly consists of an in-house fabricated large
      augmented reality (AR) screen (60  cm*40  cm) and a pair of laser-scanning 30
      lumen pico-projectors. The display is tested for different viewing
      configurations, and different display parameters, such as retro-reflective
      coefficient, eye-box size, polarization maintainability, stereo crosstalk, and
      brightness, are examined. The AR prototype display provides 75% optical
      transparency, exceptional brightness (up to 1000  cd/m2 when viewed through beam
      splitters and 350  cd/m2 with bare eyes), and negligible crosstalk in 3D mode
      (<5% and <1% when viewed through beam splitters and polarizers, respectively) for
      the working distance of up to 2 m.

PMID- 29047804
TI  - Effect of oxygen partial pressure in deposition ambient on the properties of RF
      magnetron sputter deposited Gd2O3 thin films.
AB  - Gadolinium oxide is an excellent optical material that offers high transmission
      in a wide wavelength range of 200-1600 nm and exhibits a high bulk refractive
      index of ~1.80 at 550 nm. In the present study, a set of Gd2O3 thin films has
      been deposited on fused silica substrates by RF sputtering of a Gd2O3 target
      under various O2 to Ar flow ratios. The samples have been characterized by
      grazing incidence x-ray diffraction (GIXRD) to study the long range structural
      behavior, by GIXR to study density and surface roughness of the films, by atomic
      force microscopy measurements to study morphological properties, by Rutherford
      backscattering measurements for compositional studies, and by transmission
      spectrophotometry and spectroscopic ellipsometry techniques to study their
      optical properties. It has been observed that the films deposited with 10% oxygen
      partial pressure have low density, high surface roughness, and high void content,
      which results in a low value of refractive index of this film, and film quality
      improves as oxygen partial pressure is further increased. Extended x-ray
      absorption fine structure measurement with synchrotron radiation has also been
      employed to extract local structural information around Gd sites, which has in
      turn been used to explain some of the observed macroscopic properties of the
      films.

PMID- 29047805
TI  - Phase-matching properties of LiGaSe2 for SHG and SFG in the 1.026-10.5910 MUm
      range.
AB  - This paper reports on the new experimental results for second-harmonic generation
      and sum-frequency generation in LiGaSe2 in the 1.026-10.5910 MUm range, and the
      improved Sellmeier equations that provide a good reproduction of the present
      experimental results, as well as the published data points for a Ti:Al2O3 laser
      (lambda=0.8200  MUm)-pumped optical parametric amplifier and a Nd:YAG laser
      pumped optical parametric oscillator in the mid-IR.

PMID- 29047806
TI  - Waveform width of a satellite laser altimeter illuminating on the sea surface.
AB  - The echo width is one of the most essential parameters of waveforms, which can be
      used to evaluate the ranging performance of a laser altimeter or retrieve wind
      speeds when laser pulses illuminate on the sea surface. The classical expression
      of waveform widths is not suitable for a current satellite laser altimeter
      because only the waves on the sea with smaller wavelengths can be covered by a
      satellite laser altimeter due to its small footprint. A new expression is derived
      by dividing the broadening effect of echo widths into the wind wave with small
      wavelengths and the swell cause with large wavelengths. The Geoscience Laser
      Altimeter System (GLAS) and National Centers for Environmental Prediction (NCEP)
      data are used to verify the new expression. Based on the new echo width
      expression, the ranging performance is evaluated when a laser is illuminating on
      the ocean surface. It indicates that a laser altimeter performs a better ranging
      accuracy (better than 5 cm) than when it is evaluated using the classical
      expression (worse than 6 cm) at moderate and strong winds.

PMID- 29047807
TI  - Reconstruction of polarization images from a multimode light-field imaging
      system.
AB  - The multimode light-field camera can capture spatial location and spectral and
      polarization characteristics of a target simultaneously. There is an aliasing
      effect, which causes the directly extracted image of a certain filter to include
      information from other filters. The reconstruction method proposed by Li
      (Jingzhen Li, thesis of Beihang University, 2015) can improve the accuracy of the
      polarization images, but the gray values still have gradient variations. In this
      paper, a method for reconstructing polarization images from the light-field image
      is proposed along with an aliasing model. Compared with the conventional direct
      extraction and Li's methods, the proposed method can greatly reduce energy loss,
      and the accuracy of the reconstructed image increases more than fivefold.

PMID- 29047808
TI  - Optical elements containing semitransparent wavelike films.
AB  - Novel optical elements containing semitransparent wavelike films embedded into
      the bulk of transparent material, which form a reflection image without
      transmitted light distortion, are studied. The dynamic theory of light
      diffraction by a locally periodic multilayer semitransparent wavelike film is
      developed. A simple analytical formula for near Bragg diffraction order intensity
      is obtained for the case when only one diffraction order lies within the hologram
      angular selectivity. The phase modulation of light transmitted through the
      optical element containing wavelike films is estimated for single-layer and
      multilayer wavelike films with an arbitrary shape of surface. The restrictions on
      the structure parameters for which transmitted light distortions would be
      negligible are obtained. A new type of high-quality color hologram is proposed
      and shown to be feasible by calculation of hologram diffraction efficiency and
      spectral selectivity for three colors. Other possible applications, such as
      monochrome and color head-up and head-mounted displays, and imaging on spectacle
      lenses, are discussed.

PMID- 29047809
TI  - 360-degree screen-free floating 3D image in a crystal ball using a spatially
      imaged iris and rotational multiview DFD technologies.
AB  - A rotational multiview depth-fused 3D (DFD) display and 360-deg displaying optics
      using a spatially imaged iris method are proposed to realize a 360-deg 3D image.
      This method enables displaying clear floating images in a crystal ball. Its
      symmetric optics provide clear and natural 360-deg images with smooth motion
      parallax in horizontal and vertical directions using the directional selectivity
      of a spatially imaged iris method and natural 3D images of a rotational multiview
      DFD display.

PMID- 29047810
TI  - Multi-region phase calibration of liquid crystal SLM for holographic display.
AB  - The liquid crystal spatial light modulator (SLM) is able to provide flexible
      wavefront control, whereas the initial phase and its response distortions will
      heavily influence the modulation accuracy. The currently existing calibration
      methods are tedious and time consuming. A novel multi-region calibration method
      for minimizing those distortions is proposed. The entire panel is divided into
      several local regions based on the similarity of phase response characteristic.
      The nonlinear phase response and static phase distortion of each local region are
      calibrated in the iterative division procedure. The calibration method is
      theoretically analyzed and experimentally verified. For the Jasper 4 K SLM panel,
      when five local regions are built, the root mean error of linear phase shifts is
      reduced to 0.1 rad and the compensation accuracy of the static phase distortion
      reaches 0.24 wavelength. The calibrated SLM is applied for the color holographic
      display and the results show that the reconstructed image quality is improved
      significantly. The proposed method is simpler and faster because of the
      reasonable regional division and lower calibration complexity. It could be used
      for the calibration of various phase only or complex modulators with high space
      bandwidth product in the future.

PMID- 29047811
TI  - High-efficiency and flexible generation of vector vortex optical fields by a
      reflective phase-only spatial light modulator.
AB  - The scheme for generating vector optical fields should have not only high
      efficiency but also flexibility for satisfying the requirements of various
      applications. However, in general, high efficiency and flexibility are not
      compatible. Here we present and experimentally demonstrate a solution to
      directly, flexibly, and efficiently generate vector vortex optical fields (VVOFs)
      with a reflective phase-only liquid crystal spatial light modulator (LC-SLM)
      based on optical birefringence of liquid crystal molecules. To generate the
      VVOFs, this approach needs in principle only a half-wave plate, an LC-SLM, and a
      quarter-wave plate. This approach has some advantages, including a simple
      experimental setup, good flexibility, and high efficiency, making the approach
      very promising in some applications when higher power is need. This approach has
      a generation efficiency of 44.0%, which is much higher than the 1.1% of the
      common path interferometric approach.

PMID- 29047812
TI  - Polarization singularity index sign inversion by a half-wave plate.
AB  - Inhomogeneous polarization distributions can host polarization singularities such
      as lemons, monstars, stars, flowers, spider webs, and higher-order C-points in
      optical beams. Singularities in ellipse fields are characterized by a C-point
      index and singularities in vector fields by the Poincare-Hopf index. These
      singularities can be generated by diffractive or interference methods. In this
      paper, we show that a half-wave plate (HWP) can be used for polarization
      singularity index sign inversion. The result presented here is powerful, and it
      shows the importance of a HWP in the study of polarization singularities. The HWP
      affects the entire state of polarization (SOP) distribution in the index sign
      inversion process. The concomitant global change of the SOP distribution happens
      in an orderly fashion to change the polarity of the polarization singularity
      index. This method of changing the polarity of the polarization singularity index
      by a HWP holds good both for ellipse fields as well as for vector fields.

PMID- 29047813
TI  - Unique and concise system translation matrices for evaluating optical aberration
      variations.
AB  - New unique and concise translation matrices are derived for evaluating the
      aberration variations of conceptual and real lenses when the paraxial marginal
      and chief ray paths are arbitrarily changed. They are helpful in investigating
      the general behaviors of lenses and optimizing the balanced aberrations of lens
      components in prime and zoom lenses. These new matrices, with a dimension of 9*9
      for monochromatic aberrations and a dimension of 4*4 for chromatic aberrations,
      are derived based on our earlier algorithms of which four cases with distinct
      translation factors and matrices are required according to the relationships of
      the original and new positions of the object and pupil; otherwise, division-by
      zero errors or insufficient numerical accuracy will be encountered. As a
      comparison, the new matrices have several advantages. First, by introducing four
      meaningful equivalent optical invariants, multiplying the old matrices, and
      simplifying the new matrices, they have concise expressions to significantly
      reduce the calculation time. Second, they are unique and always accurate to apply
      for all kinds of object and pupil positions without suffering any mathematical
      problems, i.e., four separated algorithms are no longer necessary. Third, due to
      the unique property, the component contributions of original aberrations to new
      aberrations can be directly evaluated and analyzed.

PMID- 29047814
TI  - Annealing properties of fiber Bragg grating UV-inscribed in boron-germanium
      codoped fiber.
AB  - In this work, we mainly focus on the investigation of the feasibility of
      production of high-temperature stable fiber Bragg grating (FBG) based on
      reduplicative alternate annealing and hydrogen loading. The experimental results
      also can demonstrate the significance of the presence of hydrogen to the thermal
      regeneration of FBGs. The gratings are characterized and variations are compared
      after each stage, including UV fabrication, annealing, and reduplicative hydrogen
      preloaded annealing. In different stages, the spectral and annealing responses of
      FBG are, respectively, investigated, as temperature increases, the Bragg
      wavelength consistently shifts to longer wavelengths; nevertheless, the
      reflection variations are distinctly discrepant. After reduplicative alternate
      annealing and hydrogen loading, the thermal stability is tremendously improved,
      and a reborn, stable grating is formed.

PMID- 29047815
TI  - Electromagnetic pulse scattering by a spacecraft nearing light speed.
AB  - Humans will launch spacecraft that travel at an appreciable fraction of the speed
      of light. Spacecraft traffic will be tracked by radar. Scattering of pulsed
      electromagnetic fields by an object in uniform translational motion at
      relativistic speed may be computed using the frame-hopping technique. Pulse
      scattering depends strongly on the velocity, shape, orientation, and composition
      of the object. The peak magnitude of the backscattered signal varies by many
      orders of magnitude, depending on whether the object is advancing toward or
      receding from the source of the interrogating signal. The peak magnitude of the
      backscattered signal goes to zero as the object recedes from the observer at a
      speed very closely approaching light speed, rendering the object invisible to the
      observer. The energy scattered by an object in motion may increase or decrease
      relative to the energy scattered by the same object at rest. Both the magnitude
      and sign of the change depend on the velocity of the object, as well as on its
      shape, orientation, and composition. In some cases, the change in total scattered
      energy is greatest when the object is moving transversely to the propagation
      direction of the interrogating signal, even though the Doppler effect is
      strongest when the motion is parallel or antiparallel to the propagation
      direction.

PMID- 29047816
TI  - Multiple-3D-object decryption based on one interference using two phase-only
      functions.
AB  - We propose a multiple-3D-object decryption scheme based on one interference using
      two beams that are from two different phase-only functions. It takes advantage of
      off-axis digital holography to extract the optical fields of multiple 3D objects,
      and respectively utilize single different decryption keys to decrypt multiple 3D
      objects in the decryption procedure. The advantages of the proposed scheme
      include the following: each 3D object can be decrypted discretionarily without
      decrypting a series of other objects earlier; no iterative algorithm is involved;
      and the decrypted image of each object can be successfully clearly distinguished.
      The feasibility of the proposed scheme is verified by the optical holograms of
      real 3D objects.

PMID- 29047817
TI  - Autofocusing imaging system based on laser ranging and a retina-like sample.
AB  - A novel autofocusing method combining active and passive techniques is proposed
      to improve autofocusing performance. The proposed method is divided into coarse
      and fine autofocusing stages. First, a laser ranging finder viewed as the active
      technique is used to obtain a reasonable initial position of the compensating
      lens group during the coarse autofocusing stage. Second, a retina-like sampling
      method is used to decrease the volume of processing data during the fine
      autofocusing stage. We developed a prototype and performed comparative
      experiments using different targets based on the proposed method and the
      traditional passive method (TPM). Under optical power of 9*, the TPM consumed 2.5
      s, while the proposed method performed at 1.3 s. The comparative experiments also
      showed that the proposed method exhibited a better anti-interference property
      than the traditional method.

PMID- 29047818
TI  - Optical-power tunable dual-wavelength laser around 1  MUm in Nd3+/Yb3+ co-doped
      phosphate glass fiber.
AB  - This work reports the generation of an optical-power tunable 1 MUm dual
      wavelength fiber laser in Nd3+/Yb3+ co-doped phosphate glass fiber under 970 nm
      and 808 nm laser diode pumping. A bidirectional free-space pump laser setup was
      adopted. An optical-power tunable dual-wavelength laser can be easily realized by
      the control of 808 nm pump power magnitude. Based on a series of laser tests
      under different pump conditions and theoretical calculation of the Nd3+->Yb3+
      energy transfer efficiency, the control mechanism was found to be the stimulated
      emission modulation of Nd3+ on Yb3+ lasing. This property is helpful to enhance
      the knowledge of the Nd3+/Yb3+ co-doping system.

PMID- 29047819
TI  - Design of a simple non-destructive detection system using P-wave lasers for
      determining the soluble solids content of apples.
AB  - The simple and nondestructive detection system studied in this work uses a near
      infrared (NIR) detector and parallel-polarized (P-wave) NIR lasers to determine
      the soluble solids content (SSC) of apples. The P-wave NIR laser in this system
      is incident into the apple's pulp at the Brewster angle to minimize the
      interference caused by interfacial reflections. After the apple has been
      illuminated by four P-wave NIR lasers that correspond to the specified
      wavelengths of the SSC chemical bonds (880, 940, 980, and 1064 nm), the
      prediction of correlation (rp2) and the root-mean-square error for prediction
      (RMSEP) of the SSC are determined via partial least square regression analysis of
      the reflectance. Our results indicate that the use of P-wave lasers at the
      Brewster angle (as the angle of incidence) and the above specified wavelengths
      for the prediction set measurement of the SSC of apples obtained an rp2 of 0.88
      and an RMSEP of 0.47 degrees Brix. These rp2 are 6% higher, and the RMSEPs are 9%
      lower, than those obtained using non-polarized lasers.

PMID- 29047820
TI  - Analytic conic constants to reduce the spherical aberration of a single lens used
      in collimated light.
AB  - We study the formation of caustic surfaces produced by conic lenses, considering
      a plane wavefront propagating parallel to the optical axis. The shape of the
      caustic can be modified by changing the parameters of the lens in such a way that
      if we are able to vanish the caustic, the optical system produces the sharpest
      diffraction-limited images. Alternatively, caustic surfaces with a large area can
      be applied to the design of non-imaging optical systems, with potential
      applications such as diffusers of light for illumination or solar concentrators.
      Here, we provide analytic equations for the conic constants, principal surfaces,
      and caustic surfaces, and also approximations at the third and fifth orders
      formed by conic lenses, in order to reduce the spherical aberration at these
      orders.

PMID- 29047821
TI  - General method of extreme surfaces for geometry optimization of the linear
      electro-optic effect on an example of LiNbO3:MgO crystals.
AB  - A general method for determining the global maximum of the linear electro-optic
      effect in crystalline materials based on the construction and analysis of extreme
      surfaces obtained as a result of the optimization procedure is proposed. The
      electrically induced optical path length changes for ordinary and extraordinary
      waves as well as the optical path difference for orthogonally polarized waves
      were used as the objective functions in the optimization. The objective functions
      were determined for units of the electric field and crystal thickness in the
      light pass direction. In the example of LiNbO3:MgO, it is shown that the maximal
      achievable given values of the optical path length change (global maxima) for
      ordinary and extraordinary waves are 119 pm/V and 277 pm/V, respectively. The
      global maximum of the optical path difference for orthogonally polarized waves is
      269 pm/V (for 632.8 nm wavelength and at room temperature). These global maxima
      are exceeded by ~1.5, 1.7, and 2.3 times the respective maximum values on direct
      cut crystals of LiNbO3:MgO and are ~5%, 9%, or 11% larger than the global maxima
      for undoped LiNbO3 crystal. This ensures a possibility to increase the energy
      efficiency by ~2.9 or 5.3 times in the case of using of LiNbO3:MgO crystals with
      optimal cuts as sensitive elements of electro-optic devices.

PMID- 29047822
TI  - Circular dichroism effect in a double-layer dolmen array nanostructure.
AB  - Chiral plasmonic nanostructures have been studied widely in past years and have
      various applications in biological sensing, negative refractive indexing, and
      analytical chemistry. Dolmen is also a commonly used nanostructure in many recent
      research papers. By placing dolmens in different directions and forming a double
      layer dolmen array (DLDA), a new nanostructure with good circular dichroism (CD)
      effect is designed in this paper. We get up to the maximum of 0.5 of CD effect
      through numerical simulation. Among three obvious resonance wavelengths of CD
      effect, magnetic dipole resonance appears in two of them and contributes to the
      origin of a strong CD effect. In these different coupling modes, the strongest
      one locating at the largest wavelength is the result of a big magnetic dipolar
      resonance generated by circulation current in two layers of dolmen together, and
      the second strongest CD effect is caused by individual magnetic dipolar resonance
      in the opposite direction located in each layer. At the weakest one, the
      circulation current disappears and only a regular electric dipolar resonance
      appears. This simulation result shows that magnetic dipolar resonance of
      plasmonic nanostructure could create a strong CD effect, and much more
      effectively in the DLDA we propose. The results can help us in designing novel
      chiral optical nanostructures and provide applications in the interactions
      between photons and electrons.

PMID- 29047823
TI  - Modeling the focusing efficiency of lobster-eye optics for image shifting
      depending on the soft x-ray wavelength.
AB  - Lobster-eye optics is widely applied to space x-ray detection missions and x-ray
      security checks for its wide field of view and low weight. This paper presents a
      theoretical model to obtain spatial distribution of focusing efficiency based on
      lobster-eye optics in a soft x-ray wavelength. The calculations reveal the
      competition mechanism of contributions to the focusing efficiency between the
      geometrical parameters of lobster-eye optics and the reflectivity of the iridium
      film. In addition, the focusing efficiency image depending on x-ray wavelengths
      further explains the influence of different geometrical parameters of lobster-eye
      optics and different soft x-ray wavelengths on focusing efficiency. These results
      could be beneficial to optimize parameters of lobster-eye optics in order to
      realize maximum focusing efficiency.

PMID- 29047824
TI  - Optical turbulence in confined media. Part II:first results using the INTENSE
      instrument.
AB  - Optical system performances can be affected by local optical turbulence created
      by its surrounding environment (telescope dome, clean room, or atmospheric
      layer). This paper follows a previous one introducing the INdoor TurbulENce
      SEnsor (INTENSE) instrument for optical turbulence characterization in a local
      area by exploitation of laser beam angle-of-arrival fluctuations. After a brief
      summary of the theoretical background, we present in this part results obtained
      using the INTENSE instrument in various optical integration testing clean rooms
      and telescope domes, each with specific air behavior conditions.

PMID- 29047825
TI  - Compact polarization-based dual-view panoramic lens.
AB  - Panoramic annular lens (PAL) is a type of special optical system that can
      transform the cylindrical side view onto a planar annular image. We propose a
      compact polarization-based dual-view panoramic lens to solve the two major
      limitations of the conventional PAL structure: large front annular lens and lack
      of forward view. Dual-view imaging capability, which is highly needed for some
      applications, is achieved by using a polarization technique. The diameter ratio
      of the proposed front PAL lens and the sensor is reduced to less than 1.5, while
      it is larger than 2.5 for traditional PAL systems, expanding its applications in
      space-confined environments.

PMID- 29047826
TI  - Astrometric distortion calibration of a portable refractor.
AB  - A compact refractor simplifies imaging stars during a total solar eclipse from
      remote, temporary locations. To achieve astrometric accuracy, cubic distortion
      terms were measured using hundreds of nighttime images. A detailed procedure is
      presented here, along with an example from a portable telescope. The results show
      that precisions down to the 20 mas level are possible with commercial equipment.

PMID- 29047827
TI  - Detecting wavefront amplitude and phase using linear phase diversity.
AB  - We propose a simplified phase diversity method based on the first-order Taylor
      expansion of the optical transfer function (OTF) as the light intensity on the
      pupil plane is not uniform but presents Gaussian distribution. By extending the
      Zernike polynomial term to the complex field, we regard the distribution of the
      light intensity as the imaginary part of the phase, which can be solved together
      with the phase aberration (the real part of the phase). The approximation of the
      OTF using the first-order Taylor expansion can simplify the relationship between
      the phase and OTF to linear relation, so that the aberration can be quickly
      solved. We present an experiment that validates the advantage of our method. The
      result shows that the modified method has a higher accuracy with less time
      compared to the traditional phase diversity algorithm, and can acquire the
      distribution of the light on the pupil plane.

PMID- 29047828
TI  - Three-dimensional surface microtopography recovery from a multifocus image
      sequence using an omnidirectional modified Laplacian operator with adaptive
      window size.
AB  - Optical microscopy enables the observation of highly magnified objects and
      material structures on microsurfaces, but it can only acquire 2D images. In order
      to observe areal features more accurately and intuitively, 3D surface
      microtopography recovery has been applied to form a 3D surface model of an object
      from its 2D image sequence. In the 3D reconstruction of the focus evaluation
      operator, we have the gray variance operator, the gray-scale difference absolute
      sum operator, the Roberts gradient operator, the Tenengrad gradient operator, the
      improved Laplace operator, etc. There are two problems with these operators: one
      is that there is no difference between (x,y) and the gray scale of the pixel in
      the diagonal direction in the field and the other is that the window size of the
      focus evaluation operator is fixed, e.g., 3*3, 5*5, etc. Thus, the size of the
      window for each pixel in the image is the same, and the small window may not
      cover enough field information while being vulnerable to noise. Large windows can
      cover more information, but they may result in a smoothing phenomenon, which
      affects the accuracy of the model. Different pixels around the field have
      different pixel colors when the size of the window is not the same. Therefore,
      this paper proposes a modified omnidirectional Laplacian operator with an
      adaptive window to automatically adjust the size of the window according to the
      color difference within the window. This also takes into consideration the pixels
      in the diagonal direction. In addition, very comprehensive verification
      experiments proved the conclusions.

PMID- 29047829
TI  - Probing methane in air with a midinfrared frequency comb source.
AB  - We employed a midinfrared frequency comb source for methane detection in ambient
      air. The transmitted spectra over a bandwidth of about 500 nm were recorded with
      an optical spectrum analyzer under various experimental conditions of different
      path lengths. The normalized absorption spectra were compared and fitted with
      simulations, yielding quantitative values of concentrations of methane and water
      vapor in the ambient air. The 3sigma detection limit was ~6.6*10-7  cm-1 in
      ambient air for a broad spectral range, achieved with a path length of ~590  m.
      This approach provides a broad spectral range, a large dynamic range, high
      sensitivity, and accurate calibration. The performed analysis of the residuals
      shows that an excellent agreement between the measured and calculated spectral
      profiles was obtained.

PMID- 29047830
TI  - In situ detection of water quality contamination events based on signal
      complexity analysis using online ultraviolet-visible spectral sensor.
AB  - The contaminant detection in water distribution systems is essential to protect
      public health from potentially harmful compounds resulting from accidental spills
      or intentional releases. As a noninvasive optical technique, ultraviolet-visible
      (UV-Vis) spectroscopy is investigated for detecting contamination events.
      However, current methods for event detection exhibit the shortcomings of noise
      susceptibility. In this paper, a new method that has less sensitivity to noise
      was proposed to detect water quality contamination events by analyzing the
      complexity of the UV-Vis spectrum series. The proposed method applied approximate
      entropy (ApEn) to measure spectrum signals' complexity, which made a distinction
      between normal and abnormal signals. The impact of noise was attenuated with the
      help of ApEn's insensitivity to signal disturbance. This method was tested on a
      real water distribution system data set with various concentration simulation
      events. Results from the experiment and analysis show that the proposed method
      has a good performance on noise tolerance and provides a better detection result
      compared with the autoregressive model and sequential probability ratio test.

PMID- 29047831
TI  - Design of a smooth freeform illumination system for a point light source based on
      polar-type optimal transport mapping.
AB  - A design method is proposed to generate smooth freeform illumination optics for a
      point light source based on the L2 optimal transport (LOT) mapping. In this
      method, the LOT mapping between an assumed circular planar source and a
      prescribed target is first obtained by solving a polar-type LOT problem. Then,
      the mapping calculated for the circular source is applied for a point light
      source. Finally, the freeform optical surface is generated by a geometric
      construction method to realize the ray mapping. As examples, a series of smooth
      surface freeform lenses are designed for a point light source to form uniform and
      complex illumination patterns on rectangular targets. The ray-tracing results
      show that all the designs achieve excellent performance with the light
      utilization efficiency eta over 0.87 (Fresnel loss considered) and the relative
      standard deviation (RSD) of the simulated illumination distribution less than
      0.051 simultaneously.

PMID- 29047832
TI  - Coded aperture design in compressive spectral imaging based on side information.
AB  - Coded aperture compressive spectral imagers (CSI) sense a three-dimensional data
      cube by using two-dimensional projections of the coded and spectrally dispersed
      input image. Recently, it has been shown that by combining spectral images
      acquired from a CSI sensor and a complementary sensor leads to substantial
      improvement in the quality of the fused image. To maximally exploit the benefits
      of the complementary information, the spatial structure of the coded apertures
      must be optimized inasmuch as these structures determine the sensing matrix
      properties and, accordingly, the quality of the reconstructed images. This paper
      proposes a method to use side information from a red-green-blue sensor to design
      the coded aperture patterns of a CSI imager, such that more detailed spatial
      images and wavelength profiles can be reconstructed. The side information is used
      as the input of an edge detection algorithm to approximate a version of the edges
      of the spectral images. The coded apertures are designed to follow the spatial
      structure determined by the estimated spectral edges, such that the high
      frequencies are promoted, leading to more detailed reconstructed spectral images.
      Simulations and experimental results indicate that when compared with random
      coded aperture structures, the designed coded apertures based on side information
      obtain up to 3 dB improvement in the quality of the reconstructed images.

PMID- 29047833
TI  - Visualization and label-free quantification of microfluidic mixing using
      quantitative phase imaging.
AB  - Microfluidic mixing plays a key role in various fields, including biomedicine and
      chemical engineering. To date, although various approaches for imaging
      microfluidic mixing have been proposed, they provide only quantitative imaging
      capability and require exogenous labeling agents. Quantitative phase imaging
      techniques, however, circumvent these problems and offer label-free quantitative
      information about concentration maps of microfluidic mixing. We present the
      quantitative phase imaging of microfluidic mixing in various types of
      polydimethylsiloxane microfluidic channels with different geometries; the
      feasibility of the present method was validated by comparing it with the results
      obtained by theoretical calculation based on Fick's law.

PMID- 29047834
TI  - N-isopropylacrylamide-based photopolymer for holographic recording of
      thermosensitive transmission and reflection gratings.
AB  - In recent years, functionalized photopolymer systems capable of holographic
      recording are in great demand due to their potential use in the development of
      holographic sensors. This work presents a newly developed N-isopropylacrylamide
      (NIPA)-based photopolymer for holographic recording in reflection and
      transmission modes. The optimized composition of the material is found to reach
      refractive index modulation of up to 5*10-3 and 1.6*10-3 after recording in
      transmission and reflection mode, respectively. In addition to fulfilling the
      requirements for holographic recording materials, the NIPA-based photopolymer is
      sensitive to temperature and has lower toxicity than acrylamide-based
      photopolymers. Possible application of the NIPA-based photopolymer in the
      development of a holographic temperature sensor is discussed.

PMID- 29047835
TI  - Uncertainty budgets for liquid waveguide CDOM absorption measurements.
AB  - Long path length liquid waveguide capillary cell (LWCC) systems using simple
      spectrometers to determine the spectral absorption by colored dissolved organic
      matter (CDOM) have previously been shown to have better measurement sensitivity
      compared to high-end spectrophotometers using 10 cm cuvettes. Information on the
      magnitude of measurement uncertainties for LWCC systems, however, has remained
      scarce. Cross-comparison of three different LWCC systems with three different
      path lengths (50, 100, and 250 cm) and two different cladding materials enabled
      quantification of measurement precision and accuracy, revealing strong wavelength
      dependency in both parameters. Stable pumping of the sample through the capillary
      cell was found to improve measurement precision over measurements made with the
      sample kept stationary. Results from the 50 and 100 cm LWCC systems, with higher
      refractive index cladding, showed systematic artifacts including small but
      unphysical negative offsets and high-frequency spectral perturbations due to
      limited performance of the salinity correction. In comparison, the newer 250 cm
      LWCC with lower refractive index cladding returned small positive offsets that
      may be physically correct. After null correction of measurements at 700 nm,
      overall agreement of CDOM absorption data at 440 nm was found to be within 5%
      root mean square percentage error.

PMID- 29047836
TI  - Lorenz curve of a light beam: evaluating beam quality from a majorization
      perspective.
AB  - We introduce a novel approach for the characterization of the quality of a laser
      beam that is not based on particular criteria for beam width definition. The
      Lorenz curve of a light beam is a sophisticated version of the so-called power-in
      the-bucket curve, formed by the partial sums of discretized joint intensity
      distribution in the near and far fields, sorted in decreasing order. According to
      majorization theory, a higher Lorenz curve implies that all measures of spreading
      in phase space, and, in particular, all Renyi (and Shannon) entropy-based
      measures of the beam width products in near and far fields, are unanimously
      smaller, providing a strong assessment of a better beam quality. Two beams whose
      Lorenz curves intersect can be considered of relatively better or lower quality
      only according to specific criteria, which can be inferred from the plot of the
      respective Lorenz curves.

PMID- 29047837
TI  - Optimization of a multibeam-pumped optical parametric amplifier.
AB  - The results of numerical simulation of the output amplifier cascade of a powerful
      laser system based on the parametric amplification of femtosecond pulses in an
      LiB3O5 crystal with multiple beams pumping are presented. The improved technique
      for choosing pump beam angles with minimal parasitic amplification is presented.
      Differences of carrier-resolving versus envelope simulations are discussed.
      Results for pulse energy, duration, and fraction of parasitic energy are
      presented. It has been established that with an increase in the number of pump
      beams up to 11 beams, the duration of the amplified pulse increases
      insignificantly from 20 to 21 fs in the case of incoherent pumping beams and
      increases to 26 fs in the case of coherent ones. At the same time, the
      amplification efficiency decreases from 23% to 21% in the first case and drops to
      10% in the second case. Influence of small-scale, self-focusing of the pump field
      interference pattern on peak intensity is discussed.

PMID- 29047838
TI  - Convolution- and Fourier-transform-based reconstructors for pyramid wavefront
      sensor.
AB  - In this paper, we present two novel algorithms for wavefront reconstruction from
      pyramid-type wavefront sensor data. An overview of the current state-of-the-art
      in the application of pyramid-type wavefront sensors shows that the novel
      algorithms can be applied in various scientific fields such as astronomy,
      ophthalmology, and microscopy. Assuming a computationally very challenging
      setting corresponding to the extreme adaptive optics (XAO) on the European
      Extremely Large Telescope, we present the results of the performed end-to-end
      simulations and compare the achieved AO correction quality (in terms of the long
      exposure Strehl ratio) to other methods, such as matrix-vector multiplication and
      preprocessed cumulative reconstructor with domain decomposition. Also, we provide
      a comparison in terms of applicability and computational complexity and closed
      loop performance of our novel algorithms to other methods existing for this type
      of sensor.

PMID- 29047839
TI  - Development of a spatially dispersed short-coherence interferometry sensor using
      diffraction grating orders.
AB  - Modern manufacturing processes can achieve good throughput by requiring that
      manufactured products be screened by better quality control exercised at a
      quicker rate. This trend in the quality control of manufactured products
      increases the need for process-oriented precision metrology capable of performing
      faster inspections and yielding valuable feedback to the manufacturing system.
      This paper presents a spatially dispersed short-coherence interferometry sensor
      using diffraction orders of the zeroth and first order for a diffraction grating
      introduced as a new compact system configuration for surface profile measurement.
      In this modified design, the diffraction grating acts as the beam
      splitter/combiner. Diffractions for the zeroth and first orders are represented
      by the reference and measurement arms, respectively, of a Michelson
      interferometer, which reduces the optical path length. This innovative design has
      been proven effective for determining the step-height repeatability in the sensor
      range from 27 nm to 22 nm for profiles spanning the step heights of the tested
      specimens.

PMID- 29047840
TI  - Sub-diffraction limit laser ablation via multiple exposures using a digital
      micromirror device.
AB  - We present the use of digital micromirror devices as variable illumination masks
      for pitch-splitting multiple exposures to laser machine the surfaces of
      materials. Ultrafast laser pulses of length 150 fs and 800 nm central wavelength
      were used for the sequential machining of contiguous patterns on the surface of
      samples in order to build up complex structures with sub-diffraction limit
      features. Machined patterns of tens to hundreds of micrometers in lateral
      dimensions with feature separations as low as 270 nm were produced in electroless
      nickel on an optical setup diffraction limited to 727 nm, showing a reduction
      factor below the Abbe diffraction limit of ~2.7*. This was compared to similar
      patterns in a photoresist optimized for two-photon absorption, which showed a
      reduction factor of only 2*, demonstrating that multiple exposures via ablation
      can produce a greater resolution enhancement than via two-photon polymerization.

PMID- 29047841
TI  - Monitoring stress changes in carbon fiber reinforced polymer composites with GHz
      radiation.
AB  - We performed proof of concept experiments to demonstrate that the reflected power
      of GHz illumination from the surface of carbon fiber reinforced polymer (CFRP)
      composites is linearly related to the stress in the material. We introduce a
      stress coefficient to describe the change in normalized power with applied
      stress, analogous to the stress-optic coefficient, because the effect is
      attributed to changes in the refractive index of the effective medium comprising
      the polymer matrix and carbon fibers. Stress coefficients of -0.549+/-0.134/GPa
      and -0.154+/-0.024/GPa were measured for two different composite materials, both
      linear in the measurement range of 40 MPa and 100 Mpa, respectively. This
      technique opens up the possibility of non-destructive evaluation of stresses in
      CFRP components for quality assurance in manufacturing and in structural health
      monitoring of in-service aerospace and automotive parts.

PMID- 29047842
TI  - Breaking camouflage and detecting targets require optic flow and image structure
      information.
AB  - Use of motion to break camouflage extends back to the Cambrian [In the Blink of
      an Eye: How Vision Sparked the Big Bang of Evolution (New York Basic Books,
      2003)]. We investigated the ability to break camouflage and continue to see
      camouflaged targets after motion stops. This is crucial for the survival of
      hunting predators. With camouflage, visual targets and distracters cannot be
      distinguished using only static image structure (i.e., appearance). Motion
      generates another source of optical information, optic flow, which breaks
      camouflage and specifies target locations. Optic flow calibrates image structure
      with respect to spatial relations among targets and distracters, and calibrated
      image structure makes previously camouflaged targets perceptible in a temporally
      stable fashion after motion stops. We investigated this proposal using laboratory
      experiments and compared how many camouflaged targets were identified either with
      optic flow information alone or with combined optic flow and image structure
      information. Our results show that the combination of motion-generated optic flow
      and target-projected image structure information yielded efficient and stable
      perception of camouflaged targets.

PMID- 29047843
TI  - Field diversity phase retrieval method for wavefront sensing in monolithic mirror
      space telescopes.
AB  - To guarantee the uniqueness of the solution for the wavefront phase, a series of
      intensity images with known phase diversities is usually needed in the current
      phase retrieval wavefront sensing methods. However, to obtain these intensity
      images with deliberately added diversity phases, some additional instruments
      (e.g., beam splitters) or operations (e.g., adjustment of the focus) are usually
      needed, which can pose a challenge for wavefront sensing in space telescopes.
      This paper proposes a new concept for retrieving the wavefront phase of
      monolithic mirror space telescopes with perturbations, where the intensity
      measurements with phase diversities are directly obtained from different field
      positions of one image, without the need for any additional instruments or
      operations. To realize this new concept, we present a modified phase diversity
      method to account for the unknown phase diversities between these intensity
      measurements based on an in-depth understanding of the net aberration fields
      induced by misalignments and figure errors. Relevant simulations for different
      cases are performed to demonstrate the feasibility and accuracy of the proposed
      method. Since in this method the phase diversities between different intensity
      measurements are mainly induced by the diversities in the field position, we call
      it the field diversity phase retrieval method. This work can present great
      facility for wavefront sensing in monolithic mirror space telescopes.

PMID- 29047844
TI  - Nanoparticle classification in wide-field interferometric microscopy by
      supervised learning from model.
AB  - Interference-enhanced wide-field nanoparticle imaging is a highly sensitive
      technique that has found numerous applications in labeled and label-free
      subdiffraction-limited pathogen detection. It also provides unique opportunities
      for nanoparticle classification upon detection. More specifically, the
      nanoparticle defocus images result in a particle-specific response that can be of
      great utility for nanoparticle classification, particularly based on type and
      size. In this work, we combine a model-based supervised learning algorithm with a
      wide-field common-path interferometric microscopy method to achieve accurate
      nanoparticle classification. We verify our classification schemes experimentally
      by blindly detecting gold and polystyrene nanospheres, and then classifying them
      in terms of type and size.

PMID- 29047845
TI  - Investigation of high optical gain in complex type-II InGaAs/InAs/GaAsSb nano
      scale heterostructure for MIR applications.
AB  - This paper reports a comprehensive theoretical study of W-shaped complex type-II
      InGaAs/InAs/GaAsSb nano-scale heterostructure consisting of two quantum wells of
      InAs material using the six-band k.p theory. The entire structure has been
      supposed to be grown on InP substrate. In order to optimize the optical gain, the
      probability densities of electrons and holes were optimized in the
      heterostructure. Following these calculations, dispersion relations for electron
      and hole energies, and transverse electric and transverse magnetic polarizations
      dependent dipole matrix elements and momentum matrix elements were calculated
      and, finally, the optical gain in both polarization modes was calculated. For
      this optimized complex heterostructure, a very high optical gain of the order of
      ~4500  cm-1 in the regime of mid-infrared wavelength ~3.2  MUm has been achieved.
      The results suggest that the designed nano-heterostructure may be utilized for
      mid-infrared region (MIR) applications such as chemical and bio-molecular sensing
      of molecules, for the applications of spectroscopy in the "fingerprint region" of
      molecular science, and for detection of atmospheric gases that respond to 3.2 MUm
      wavelength.

PMID- 29047846
TI  - Integrated FP/RFBG sensor with a micro-channel for dual-parameter measurement
      under high temperature.
AB  - An integrated sensor via overlapping a micro Fabry-Perot (MFP) cavity with a
      micro-channel on a regenerated fiber Bragg grating (RFBG) is constructed for dual
      parameter sensing of temperature, strain, and gas pressure under a high
      temperature (600 degrees C). The MFP is fabricated by using a 157 nm micro
      machining on H2-loaded bendinsensitive fiber. A fiber Bragg grating (FBG) is
      inscribed at the same position of the MFP using 248 nm laser exposure, and then
      successfully regenerated after a required annealing process which enhances the
      strain sensitivity of MFP more than three times. The micro-channel created on the
      MFP is used to improve gas pressure sensitivity of the MFP nearly 100 times.
      Since the MFP and RFBG have different sensitivities to gas pressure, strain, and
      temperature, the sensor head could be used to perform dual-parameter measurement
      by simultaneous measurement of high temperature and strain, and high temperature
      and gas pressure.

PMID- 29047847
TI  - Coherent beam combining of fiber lasers using a CDMA-based single-frequency
      dithering technique.
AB  - Coherent beam combination (CBC) is a promising method to obtain high-power and
      high-brightness laser output. In this paper, we present a novel single-frequency
      dithering technique based on code division multiple access (CDMA). By using
      orthogonal phase control signals, the number of channels can be increased and the
      phase control speed in the coherent beam combination system can be boosted. The
      design method and coding expression of orthogonal signals, as well as the
      relevant simulations and experiments of the designed signals, have been
      demonstrated. In the experiment, we design four orthogonal signals and realize
      the phase locking of five channels. When the phase control system is in the
      closed loop, the residual phase error is less than lambda/30 and the phase
      control speed of the CBC system is increased to nearly eleven times compared with
      that of the single-frequency dithering technique.

PMID- 29047848
TI  - Interaction of two singular Lissajous lines in free space.
AB  - The interaction of two singular Lissajous lines emergent from a polychromatic
      vector beam is studied. It is shown that singular Lissajous lines disappear with
      propagation; meanwhile Lissajous singularities take place. The handedness
      reversal, the changes in the shape of Lissajous figures, and the degree of
      polarization of Lissajous singularities, as well as the creation and annihilation
      of a single singularity, may appear by varying the control parameters. In
      addition, the transformation of the shape of line h=0, the creation and
      annihilation of pairs of Lissajous singularities not only with opposite
      topological charge and same handedness, but also with same degree of
      polarization, take place with propagation.

PMID- 29047849
TI  - Dispersed-fringe-accumulation-based left-subtract-right method for fine co
      phasing of a dispersed fringe sensor.
AB  - In this paper, a dispersed-fringe-accumulation (DFA)-based left-subtract-right
      (LSR) piston estimation method (DFA-LSR), in which the dispersed fringe image is
      accumulated in the dispersed direction, and then the LSR method is used to
      estimate the piston error, is proposed for dispersed fringe sensors (DFS) in the
      fine co-phasing stage. The DFS is usually used to detect the piston errors
      (optical path difference) between different segmented mirrors or synthetic
      aperture telescopes. The DFA-LSR makes up for the shortcomings of the main peak
      position (MPP) method, which suffers from the constant offset in the pixel
      counts. The analysis and experiment results show that the proposed method can
      keep relatively better performance even at the condition of poor signal-to-noise
      ratio, compared with the MPP method in fine co-phasing stage.

PMID- 29047850
TI  - 1  kHz, 96  W pulse-burst picosecond laser system with six equal spacing and
      amplitude pulses.
AB  - An average power of 96 W pulse-bursts picosecond laser system at a pulse
      repetition frequency of 1 kHz was reported with six pulses in bursts. Pulses in
      bursts have equal spacing and amplitude; spacing between each pulse was 800 ps,
      which repetition rate was up to gigahertz. The beam quality of M2 factor was less
      than 3, and pulse width was 50 ps. Pulses from a Nd:YVO4 mode-locked laser were
      broadened to 115 ps by a volume-Bragg grating and each pulse was divided into six
      pulses by beam splitter mirrors to obtain seed bursts. A Nd:YAG regenerative
      amplifier and two stages of single passed high gain Nd:YAG amplifier with
      serrated aperture were applied to achieve high power.

PMID- 29047851
TI  - Self-calibrating phase-shifting interferometry of three unequal phase steps by
      fitting background light to a polynomial of degree K.
AB  - This paper presents a novel non-iterative and robust algorithm in phase-shifting
      interferometry of three unknown and unequal phase steps. First, the modulation
      light and the object phase are algebraically eliminated; second, the background
      light is approximated to a 2-D polynomial of degree K and estimated by applying
      the least squares method; third the phase steps are obtained, and finally, the
      object phase is computed. This idea is theoretically described and verified
      numerically and experimentally for several values of K.

PMID- 29047852
TI  - Advanced modeling of a moderate-resolution holographic spectrograph.
AB  - In the present article we consider an accurate modeling of a spectrograph with a
      cascade of volume-phase holographic gratings. The proposed optical scheme allows
      us to detect spectra in an extended wavelength range without gaps, providing
      relatively high spectral resolution and high throughput. However, modeling and
      minimization of possible cross-talk between gratings and stray light in such a
      scheme represents a separate task. We use analytical equations of the coupled
      wave theory together with rigorous coupled-wave analysis to optimize the gratings
      parameters and further apply the latter together with a non-sequential ray
      tracing algorithm to model propagation of beams through the spectrograph. The
      results show relatively high throughput up to 53% and the absence of any
      significant cross-talk or ghost images, even for ordinary holograms recorded on
      dichromated gelatin.

PMID- 29047853
TI  - Scanning high-power continuous wave laser-generated bulk acoustic waves.
AB  - The ultrasonic bulk waves generated by a high-power continuous laser scanning
      along the surface of aluminum material were theoretically investigated. Although
      the temperature rise generated by this scanning laser irradiation was small, it
      provided a large temperature gradient, which was able to generate measurable
      ultrasonic waves. Detailed discussions were given to the influence of scanning
      speed on the generation propagation direction and the amplitude of the wavefront.
      The longitudinal and transverse waves would be generated in the material only
      when the scanning speeds reached a certain range. What's more, the amplitude of
      the wavefronts were significantly enhanced if the wavefront angle controlled by
      the scanning speed matched with the propagation direction of the ultrasound. In
      summary, it expounded a method to obtain the ultrasonic signal of direction,
      controlled from the perspective of numerical simulation, as long as the scanning
      speed met the requirements.

PMID- 29047854
TI  - Measurement of water vapor using an imaging field-widened spatial heterodyne
      spectrometer.
AB  - Spatial heterodyne spectroscopy (SHS) has been successfully applied to measure
      variations in water vapor pressure in the lab. An imaging system is combined with
      a monolithic field-widened SHS to observe a white-light source through a 1 m
      length water vapor cell that is designed to produce predictable variations in the
      water vapor pressure. The performance of the spectrometer design is examined by
      comparing spectra simulated using a radiative transfer model to observed spectra
      at several cell pressures. The intended application of the instrument to
      vertically resolve the water vapor profile in the upper troposphere and lower
      stratosphere using limb-scattered radiation in a vibrational band of water (1363
      1366 nm) is also introduced.

PMID- 29047855
TI  - Mapping of spectral signatures with snapshot spectral imaging.
AB  - We propose a snapshot spectral imaging method that enables direct reconstruction
      of spatial maps for spectral signatures of given materials using a monochromatic
      image sensor. An image-plane array of dispersive shapers converts an aerial image
      of an object into a tailored mixture of spectral and spatial data that is sensed
      and digitally processed to reconstruct weight coefficients of the spectral
      signatures. The feasibility of the method is proven by computer simulations.

PMID- 29047856
TI  - Fabrication of asymmetric long-period gratings in polarization-maintaining fiber
      with a CO2 laser.
AB  - We propose the fabrication of the long-period fiber gratings (LPFGs) in a panda
      polarization-maintaining fiber (PMF) using a two-step CO2 laser writing method.
      The first laser irradiation was aligned along one of the axes of the PMF and the
      grating with high contrast can be written after several laser scannings. The
      second irradiation was performed by rotating the PMF so that the other axis of
      the fiber aligns toward the laser exposure. New transmission dips can be observed
      when the first irradiation is along the slow axis and the second one is along the
      fast axis of the PMF. The stress relaxation effect of the stress-applying parts
      due to the laser heating was investigated theoretically and experimentally, which
      is believed to be dominant for the fabrication of the LPFGs in the PMFs by a CO2
      laser.

PMID- 29047857
TI  - Optimization technique for rolled edge control process based on the acentric tool
      influence functions.
AB  - In the process of computer controlled optical surfacing (CCOS), the
      uncontrollable rolled edge restricts further improvements of the machining
      accuracy and efficiency. Two reasons are responsible for the rolled edge problem
      during small tool polishing. One is that the edge areas cannot be processed
      because of the orbit movement. The other is that changing the tool influence
      function (TIF) is difficult to compensate for in algorithms, since pressure step
      appears in the local pressure distribution at the surface edge. In this paper, an
      acentric tool influence function (A-TIF) is designed to remove the rolled edge
      after CCOS polishing. The model of A-TIF is analyzed theoretically, and a control
      point translation dwell time algorithm is used to verify that the full aperture
      of the workpiece can be covered by the peak removal point of the tool influence
      functions. Thus, surface residual error in the full aperture can be effectively
      corrected. Finally, the experiments are carried out. Two fused silica glass
      samples of 100  mm*100  mm are polished by traditional CCOS and the A-TIF method,
      respectively. The rolled edge was clearly produced in the sample polished by the
      traditional CCOS, while residual errors do not show this problem the sample
      polished by the A-TIF method. Therefore, the rolled edge caused by the
      traditional CCOS process is successfully suppressed during the A-TIF process. The
      ability to suppress the rolled edge of the designed A-TIF has been confirmed.

PMID- 29047858
TI  - Opto-mechanical design of a dispersive artificial eye.
AB  - We present an opto-mechanical artificial eye that can be used for examining multi
      wavelength ophthalmic instruments. Standard off-the-shelf lenses and a refractive
      index-matching fluid were used in the creation of the artificial eye. In addition
      to dispersive properties, the artificial eye can be used to simulate refractive
      error. To analyze the artificial eye, a multi-wavelength Hartmann-Shack
      aberrometer was used to measure the longitudinal chromatic aberration and the
      possibility of inducing refractive error. Off-axis chromatic aberrations were
      also analyzed by imaging through the artificial eye at two discrete wavelengths.
      Possible extensions to the dispersive artificial eye are also discussed.

PMID- 29047859
TI  - Movement flatness error measurement based on an astigmatic method.
AB  - The movement flatness error is one of the critical parameters of motorized stage
      performance. In this work, the measurement of the movement flatness error based
      on an astigmatic method is proposed, in which the focus error signal is detected
      and used to analyze the movement flatness error. The theoretical derivation and
      analysis are presented, and the experimental system is established accordingly.
      The experimental results indicate that our measurement method and established
      system exhibit an accuracy of less than +/-100  nm. The movement flatness error
      of an x-y stepping motorized stage is measured using the established system, and
      the movement flatness error profile is mapped; it is determined that the maximum
      movement flatness error is within 1.3 MUm in our experiment. The proposed method
      is hence proven to be an effective way of measuring the movement flatness error
      of motorized stages.

PMID- 29047860
TI  - Fourier analysis of phase-shifting algorithms for amplitude measurement of
      interference fringe.
AB  - This paper analyses the detuning error in determining the fringe amplitude with
      phase-shifting interferometry (PSI) algorithms. The detuning error occurs when
      the phase-shift step size is not calibrated. The PSI algorithm is treated as a
      quadrature filter and the analysis is based on the filter function (FF) of the
      PSI algorithm. A mathematical expression has been derived showing that the
      detuning error consists of a bias error and a 2phi dependent error, where phi is
      the fringe phase. Examples of PSI algorithms are investigated. Computer
      simulations are performed to check the theoretical detuning errors for the PSI
      algorithms.

PMID- 29047861
TI  - Mid-infrared supercontinuum generation in multimode As2 Se3 chalcogenide photonic
      crystal fiber.
AB  - We rigorously investigated the mid-infrared supercontinuum generation in a
      multimode As2Se3 chalcogenide photonic crystal fiber (PCF). We studied the impact
      of the intermodal nonlinear effects on the nonlinear propagation of the
      fundamental and high-order modes. By solving the multimode generalized nonlinear
      Schrodinger equation, we have predicted the generation of a very broadband
      supercontinuum in both polarizations of the fundamental mode spanning from 2 to
      11 MUm at -20  dB in only 5 cm PCF length. The proposed study confirms that the
      energy transfer occurs only between the optical degenerate modes when propagating
      in the multimode chalcogenide PCF in the mid-infrared region.

PMID- 29047862
TI  - Learning-based focusing through scattering media.
AB  - We present a machine-learning-based method for light focusing through scattering
      media. In this method, the optical process in a scattering medium is
      computationally inverted based on a nonlinear regression algorithm with a number
      of training input-output pairs through the medium, and an input optimized for a
      target output is calculated. We experimentally demonstrate focusing via a process
      involving randomness due to a scattering medium and nonlinearity due to double
      modulation with a spatial light modulator. Our approach realizes model-free
      control of optical fields, where optical processes or models are unknown.

PMID- 29047863
TI  - Ultra-compact air-mode photonic crystal nanobeam cavity integrated with bandstop
      filter for refractive index sensing.
AB  - We propose and investigate an ultra-compact air-mode photonic crystal nanobeam
      cavity (PCNC) with an ultra-high quality factor-to-mode volume ratio (Q/V) by
      quadratically tapering the lattice space of the rectangular holes from the center
      to both ends while other parameters remain unchanged. By using the three
      dimensional finite-difference time-domain method, an optimized geometry yields a
      Q of 7.2*106 and a V~1.095(lambda/nSi)3 in simulations, resulting in an ultra
      high Q/V ratio of about 6.5*106(lambda/nSi)-3. When the number of holes on either
      side is 8, the cavity possesses a high sensitivity of 252 nm/RIU (refractive
      index unit), a high calculated Q-factor of 1.27*105, and an ultra-small effective
      V of ~0.758(lambda/nSi)3 at the fundamental resonant wavelength of 1521.74 nm.
      Particularly, the footprint is only about 8*0.7  MUm2. However, inevitably our
      proposed PCNC has several higher-order resonant modes in the transmission
      spectrum, which makes the PCNC difficult to be used for multiplexed sensing.
      Thus, a well-designed bandstop filter with weak sidelobes and broad bandwidth
      based on a photonic crystal nanobeam waveguide is created to connect with the
      PCNC to filter out the high-order modes. Therefore, the integrated structure
      presented in this work is promising for building ultra-compact lab-on-chip sensor
      arrays with high density and parallel-multiplexing capability.

PMID- 29047864
TI  - Simultaneous measurement of refractive index and temperature based on SPR in D
      shaped MOF.
AB  - A surface plasmon resonance (SPR) sensor based on D-shaped microstructured
      optical fiber (MOF) is proposed to realize the simultaneous measurement of
      refractive index (RI) and temperature. The D-shaped flat surface coated with a
      gold layer is in direct contact with analyte as a sensing channel of RI, and one
      of the air holes near the fiber core is filled with chloroform to detect
      temperature. Two separate channels and birefringence caused by the asymmetric
      structure can distinguish the variations of RI and temperature independently,
      thus completely solving the cross-sensitivity problem. This is the first time to
      realize the simultaneous measurement of multiple parameters without matrix
      equations, to the best of our knowledge. Results show that the y-polarized peak
      supported by channel I only shifts with RI variation and is unaffected by the
      temperature floating. Similarly, the x-polarized peak supported by channel II is
      only influenced by the change of temperature in the external environment. The
      effect of gold layer thickness is investigated numerically, and the sensor
      sensitivity is identified both in wavelength and amplitude interrogations. This
      work is very helpful for the design and implementation of a highly sensitive,
      real-time, and distributed SPR sensor for multi-parameter measurement
      applications.

PMID- 29047866
TI  - Three-dimensional image authentication scheme using sparse phase information in
      double random phase encoded integral imaging.
AB  - In recent years, many studies have focused on authentication of two-dimensional
      (2D) images using double random phase encryption techniques. However, there has
      been little research on three-dimensional (3D) imaging systems, such as integral
      imaging, for 3D image authentication. We propose a 3D image authentication scheme
      based on a double random phase integral imaging method. All of the 2D elemental
      images captured through integral imaging are encrypted with a double random phase
      encoding algorithm and only partial phase information is reserved. All the
      amplitude and other miscellaneous phase information in the encrypted elemental
      images is discarded. Nevertheless, we demonstrate that 3D images from integral
      imaging can be authenticated at different depths using a nonlinear correlation
      method. The proposed 3D image authentication algorithm can provide enhanced
      information security because the decrypted 2D elemental images from the sparse
      phase cannot be easily observed by the naked eye. Additionally, using sparse
      phase images without any amplitude information can greatly reduce data storage
      costs and aid in image compression and data transmission.

PMID- 29047865
TI  - Reflectance bandwidth and efficiency improvement of light-emitting diodes with
      double-distributed Bragg reflector.
AB  - Distributed Bragg reflectors (DBR) with metal film on the bottom have been
      demonstrated to further improve the light output power of GaN-based light
      emitting diodes (LEDs). Periods of TiO2/SiO2 stacks, thickness of metal film, and
      material of metallic reflector were designed and optimized in simulation
      software. The maximal bandwidth of double-DBR stacks have reached up to 272 nm,
      which was 102 nm higher than a single-DBR stack. The average reflectance of LEDs
      with wavelength from 380 nm to 780 nm in double-DBR stacks is 95.09% at normal
      incident, which was much higher than that of a single-DBR stack whose average
      reflectance was 91.38%. Meanwhile, maximal average reflectance of LEDs for double
      DBR stacks with an incident angle from 0 to 90 degrees  was 97.41%, which was
      3.2% higher than that of a single-DBR stack with maximal average reflectance of
      94.21%. The light output power of an LED with double-DBR stacks is 3% higher than
      that of an LED with a single-DBR stack, which was attributed to high reflectance
      of double-DBR stacks.

PMID- 29047867
TI  - Wide-angle broadband terahertz metamaterial absorber with a multilayered
      heterostructure.
AB  - In this paper, a wide-angle broadband perfect absorber is composed of a
      periodical metamaterial heterostructure. The structure is designed according to
      the concept that the metamaterial absorber's resonant frequency range can be
      manipulated by adjusting the filling factor of a bi-insulator heterostructure.
      The calculated results reveal that the four-layer herostructure has four perfect
      absorption peaks at the range of the terahertz frequency band. The related
      absorption bandwidth is 300 GHz and the average absorptivity is 98.6%. At the
      same time, the structure is insensitive to the incident angle.

PMID- 29047868
TI  - Correction of numerical aperture effect on reflection phase measurement using a
      thick-gap Fabry-Perot etalon.
AB  - We propose a method for the measurement of the reflection phase using a thick-gap
      Fabry-Perot (FP) etalon interferometry technique with correction for the
      numerical aperture effect of the optical setup. The setup is first calibrated
      using a known sample by comparing the reflectance from a two-beam interference
      model for the FP etalon with experimental data. We then apply the correction to a
      sample of interest and obtain the reflection phase of the sample. Our method can
      be used to measure the reflection phase of a small sample and could lead to
      practical applications in optical characterization of metamaterials. Moreover,
      the principle of our approach could be generalized to other systems in the
      correction of numerical aperture effect due to microscopic objectives.

PMID- 29047869
TI  - Calibration and data extraction in nonoptimized Mueller matrix polarimeters.
AB  - We present a method for calibration and data extraction for a nonoptimized
      Mueller matrix polarimeter. The advantage of this type of method is a reduction
      in measurement time for multiwavelength systems or in systems with slow response
      times. The calibration process requires the measurement of four known
      polarization devices. Here we use free-space transmission, a horizontal and a
      vertical linear polarizer, and a quarter-wave retarder with its fast axis at 30
      degrees  to the horizontal. Experimental measurements of rotating quarter-wave
      and half-wave retarders show that accurate results can be obtained with the
      proposed method.

PMID- 29047870
TI  - Optimized design of six-wave fiber optical parametric amplifiers by using a
      genetic algorithm.
AB  - A governing equation of the six-wave fiber optical parametric amplifier (FOPA)
      for the power and phase difference evolution of the six interacting waves is
      deduced. To optimize the gain of the six-wave FOPA, a multivariate stochastic
      optimization algorithm, i.e., the genetic algorithm (GA), is applied. The effect
      of pump depletion on the gain characteristic of the six-wave FOPA is emphasized
      and the effect of the fiber length, the wavelength, and the power of two pumps on
      bandwidth, flatness, and magnitude of the gain spectrum has also been studied. A
      broader and flatter six-wave FOPA gain is obtained by adopting optimum design
      parameters, which theoretically provide a uniform gain of 65 dB with 0.3 dB
      uniformity over a 110 nm bandwidth for the six-wave FOPA.

PMID- 29047871
TI  - Experimental evaluation of a 3D wavelet-based phase recovery method in temporal
      speckle pattern interferometry.
AB  - We test the performance of a phase recovery method based on a three-dimensional
      directional wavelet transform applied to the intensity signal measured by
      temporal speckle pattern interferometry (TSPI). We present and discuss several
      sources of uncertainty by analyzing experimental datasets recorded for an in
      plane interferometer without introducing a temporal carrier. The dynamic phase
      data measured with the proposed method are compared with those obtained from the
      well-known one-dimensional Fourier transform phase recovery technique. In the
      Fourier method, the filtered Fourier transform for each intensity pixel is
      evaluated along the temporal direction. In contrast, the three-dimensional
      directional wavelet transform method uses the information of adjacent pixels and
      then increases the performance of the recovered dynamic phase results. The
      advantages and limitations of the three-dimensional directional wavelet transform
      approach are discussed, and a summary of conclusions from the analysis of TSPI
      data is also given.

PMID- 29047872
TI  - Utilization of complex-valued signals in a white-light scanning interferometer
      for accurate measurement of a surface profile.
AB  - Complex-valued interference signals (CVISs) of a white-light scanning
      interferometer (WLSI) and a spectrally resolved interferometer (SRI) are obtained
      from their real-valued interference signals through Fourier transform. First the
      phase distribution in the CVIS of the SRI indicates a dispersion phase caused by
      two sides of unequal length in a cubic beam splitter, and the magnitude of the
      dispersion phase changes linearly along a horizontal direction of the beam
      splitter. Next the dispersion phase with a different magnitude is subtracted from
      the spectral phase in Fourier transform of the CVIS of the WLSI. Through inverse
      Fourier transform of this spectral distribution, a dispersion-free CVIS is
      obtained, and the position of zero phase nearest to the position of amplitude
      maximum provides a surface profile measured accurately with an error less than 4
      nm after 2pi corrections, while a position calculated by the linear component of
      the spectral phase causes measurement error less than 12 nm.

PMID- 29047873
TI  - GPU-based acceleration and mesh optimization of finite-element-method-based
      quantitative photoacoustic tomography: a step towards clinical applications.
AB  - Finite element method (FEM)-based time-domain quantitative photoacoustic
      tomography (TD-qPAT) is a powerful approach, as it provides highly accurate
      quantitative imaging capability by recovering absolute tissue absorption
      coefficients for functional imaging. However, this approach is extremely
      computationally demanding, and requires days for the reconstruction of one set of
      images, making it impractical to be used in clinical applications, where a large
      amount of data needs to be processed in a limited time scale. To address this
      challenge, here we present a graphic processing unit (GPU)-based parallelization
      method to accelerate the image reconstruction using FEM-based TD-qPAT. In
      addition, to further optimize FEM-based TD-qPAT reconstruction, an adaptive
      meshing technique, along with mesh density optimization, is adopted. Phantom
      experimental data are used in our study to evaluate the GPU-based TD-qPAT
      algorithm, as well as the adaptive meshing technique. The results show that our
      new approach can considerably reduce the computation time by at least 136-fold
      over the current central processing unit (CPU)-based algorithm. The quality of
      image reconstruction is also improved significantly when adaptive meshing and
      mesh density optimization are applied.

PMID- 29047874
TI  - Optimized calibration methodology of VIIRS day-night band low-gain stage using a
      solar diffuser.
AB  - An enhanced methodology of the standard on-orbit calibration of the day-night
      band (DNB) of the visible infrared imaging radiometer suite on board the Suomi
      National Polar-orbiting Partnership satellite is presented, specifically for the
      low-gain stage. The range of the "sweet spot" for the fully illuminated scans in
      the calibration events is expanded from 4 degrees  to 7.8 degrees  in order to
      increase the number of fully illuminated scans to 72, which then permits a
      complete calibration of the DNB to be carried out within one orbit for all 36
      aggregated modes and the two mirror sides. This improves over the current
      operational methodology, which is with a more restricted range for the sweet spot
      that requires multiple orbits to complete a calibration. The expansion
      necessarily requires the expansion of a key calibration input, the product of the
      bidirectional reflectance factor of the solar diffuser (SD) with the vignetting
      function describing the transmission of the attenuation screen in front of the SD
      port, or BVP for short. The expanded BVP is derived by fitting the function in
      three separate intervals and joining them smoothly to form a single function.
      Additional enhancements include the adaptation of the previously improved SD
      degradation and all other improvements developed for reflective solar bands from
      the previous work. The time-dependent relative spectral response is also
      characterized and implemented, and its impact and improvements are studied and
      discussed. The result shows that the improved DNB calibration coefficients are
      more stable and smooth, and less noisy.

PMID- 29047875
TI  - Improved-resolution millimeter-wave imaging through structured illumination.
AB  - A resolution-improved active millimeter-wave (MMW) imaging structure, based on
      the theory of structured illumination, is proposed in this paper. The structured
      illumination is a well-defined concept for surpassing the diffraction limit in
      optical microscopy, where imposing grating patterns on the targeted object could
      help in moving the object frequency spectrum along the desired direction in the
      spatial frequency domain. This frequency shift helps in passing different parts
      of the object's frequency spectrum through the diffraction filter. The
      combination of resultant images provides a framework to pass a wider frequency
      band of the object, thereby achieving super-resolution. This idea has not yet
      been employed for MMW image resolution improvement due to practical limitations
      in producing the desired grating patterns. Therefore, a desired fringe pattern is
      produced here and tailored for a MMW imaging system through antenna array
      synthesis. In the proposed scheme, the structured illumination has been
      implemented for improving the MMW image resolution. Furthermore, an adaptive
      approach has been proposed in order to generalize the structure for resolution
      improvement in all required directions in a very fast manner. Electromagnetic
      simulation results show at most twofold improvement in the image resolution
      through the proposed MMW imaging structure.

PMID- 29047876
TI  - Modeling of surface topography on diamond-turned spherical and freeform surfaces.
AB  - Single-point diamond turning machines are capable of generating high-quality
      spherical and freeform surfaces. However, there are inevitable tool marks on the
      diamond-turned surfaces. Although several models have been proposed to describe
      the surface topography of a flat surface, there is a lack of a more general model
      to describe spherical and freeform surfaces. In this paper, we propose a model to
      estimate the surface topography of the diamond-turned spherical and freeform
      surfaces. The model takes into consideration the basic cutting parameters as well
      as the dominant relative vibration components between the diamond tool and the
      workpiece in both infeed and feeding directions. We first discuss the principles
      and create a model for spherical surfaces. The model is then extended to describe
      more general freeform surfaces. We also show how the micro-waviness of the
      diamond tool impacts the surface topography. Finally, we conduct a series of face
      cutting experiments and conclude that there is good correlation between the model
      and the experimental results.

PMID- 29047877
TI  - High-speed combustion diagnostics in a rapid compression machine by broadband
      supercontinuum absorption spectroscopy.
AB  - The first results under fired internal combustion engine conditions based on a
      supercontinuum absorption spectrometer are presented and discussed. Temperature,
      pressure, and water mole fraction are inferred simultaneously from broadband H2O
      absorbance spectra ranging from 1340 nm to 1440 nm. The auto-ignition combustion
      process is monitored for two premixed n-heptane/air mixtures with 10 kHz in a
      rapid compression machine. Pressure and temperature levels during combustion
      exceed 65 bar and 1900 K, respectively. To allow for combustion measurements, the
      robustness of the spectrometer against beam steering has been improved compared
      to its previous version. Additionally, the detectable wavelength range has been
      extended further into the infrared region to allow for the acquisition of
      distinct high-temperature water transitions located in the P-branch above 1410
      nm. Based on a theoretical study, line-of-sight (LOS) effects introduced by
      temperature stratification on the broadband fitting algorithm in the complete
      range from 1340 nm to 1440 nm are discussed. In this context, the recorded
      spectra during combustion were evaluated only within a narrower spectral region
      exhibiting almost no interference from low-temperature molecules (here, P-branch
      from 1410 nm to 1440 nm). It is shown that this strategy mitigates almost all of
      the LOS effects introduced by cold molecules and the evaluation of the spectrum
      in the entirely recorded wavelength range at engine combustion conditions.

PMID- 29047878
TI  - Key-length analysis of double random phase encoding.
AB  - Double random phase encoding (DRPE) is a classical optical symmetric-key
      encryption method. DRPE prevents the key length from being determined because of
      its redundancy between encryption and decryption, unlike digital symmetric-key
      cryptographies. In our study, we numerically analyzed the key length of DRPE
      based on key-space analysis. We estimated the key length of DRPE by calculating
      the inverse value of the cumulative probability of the normal distribution that
      was estimated from samples of DRPE and then discuss security against brute-force
      attacks.

PMID- 29047879
TI  - Method for simultaneously calibrating peak retardation and static retardation of
      a photoelastic modulator.
AB  - A method for simultaneously calibrating the peak retardation and static
      retardation of a photoelastic modulator (PEM) is proposed. By optimizing the
      polarization modulation system, the normalized fundamental frequency components
      of the modulation signals are obtained to calculate the peak retardation and
      static retardation of the PEM. The calibration result is immune to fluctuations
      of the incident light intensity and can be used to correct the deviation of the
      photoelastic modulation detection results. In our experiments, the average
      deviation between measured peak retardations and corresponding set values is
      0.0339 rad. The standard deviation between the measured static retardations and
      the average measured value is 0.0003 rad. The calibration method has a high
      sensitivity, since the large gradient of the first-order Bessel function when the
      peak retardation is less than 1 rad. The experimental results are consistent with
      the theoretical analysis.

PMID- 29047880
TI  - Fiber-coupled LED gas sensor and its application to online monitoring of
      ecoefficient dielectric insulation gases in high-voltage circuit breakers.
AB  - Novel dielectric insulation gases used as alternatives to sulfur hexafluoride in
      gas-insulated switchgear (GIS) include several mixtures containing fluorinated
      organic compounds. We developed a fiber-optic analyzer enabling concentration
      measurement of fluoroketones used in medium- and high-voltage switchgear
      applications by ABB, with concurrent compensation of disturbing effects caused by
      dust and dirt. The sensor enables measurements in GIS and even in operating high
      voltage circuit breakers. The online availability of concentration readings of
      fluoroketones is important for development tests, but can also be applied for
      monitoring or diagnostics of field installations.

PMID- 29047881
TI  - Optimization method of star tracker orientation for sun-synchronous orbit based
      on space light distribution.
AB  - Star trackers, optical attitude sensors with high precision, are susceptible to
      space light from the Sun and the Earth albedo. Until now, research in this field
      has lacked systematic analysis. In this paper, we propose an installation
      orientation method for a star tracker onboard sun-synchronous-orbit spacecraft
      and analyze the space light distribution by transforming the complicated relative
      motion among the Sun, Earth, and the satellite to the body coordinate system of
      the satellite. Meanwhile, the boundary-curve equations of the areas exposed to
      the stray light from the Sun and the Earth albedo were calculated by the
      coordinate-transformation matrix under different maneuver attitudes, and the
      installation orientation of the star tracker was optimized based on the boundary
      equations instead of the traditional iterative simulation method. The simulation
      and verification experiment indicate that this installation orientation method is
      effective and precise and can provide a reference for the installation of sun
      synchronous orbit star trackers free from the stray light.

PMID- 29047882
TI  - Method proposing a slow light ring resonator structure coupled with a metal
      dielectric-metal waveguide system based on plasmonic induced transparency.
AB  - We demonstrate the analogue of electromagnetically induced transparency (EIT) in
      a metal-dielectric-metal (MDM) plasmonic waveguide. Plasmonic induced
      transparency is a method similar to EIT. In this paper, a plasmonic MDM waveguide
      is proposed by using an ellipse shaped side-coupled ring resonator and simulated
      by finite difference time domain. Plasmonics as a new field of chip-scale
      technology is an interesting substrate, which is used to propose and numerically
      investigate a novel MDM structure. The aforementioned framework is a 2*2
      plasmonic ring resonator, employing gold as a metal and polymethyl methacrylate
      as a dielectric. Simulations show that a transparent window is located at 1550 nm
      and signal wavelength is assumed to be 860 nm, which is the phenomenon of
      plasmonic induced transparency. The velocity of the plasmonic mode can be
      considerably slowed while propagating along the MDM bends. Our proposed
      configuration may thus be applied to storing and stopping light in plasmonic
      waveguide bends. This plasmonic waveguide system may find important applications
      for multichannel plasmonic filters, nano-scale optical switching, delay time
      devices, and slow-light devices in highly integrated optical circuits and
      networks. In comparison with our previous theoretical work based on circular
      shaped ring resonators, it is shown that ellipse shaped ring resonators
      demonstrate better specifications with a slow down factor estimated to be more
      than 30.

PMID- 29047883
TI  - Analysis and manipulation of the induced changes in the state of polarization by
      mirror scanners.
AB  - The induced polarization effects of metal-coated mirrors were studied in the
      configurations of one- and two-mirror lidar scanners as a function of azimuth and
      elevation angles. The theoretical results were verified experimentally for three
      types of mirrors (custom enhanced gold, off-the-shelf protected gold, and
      protected aluminum). A method was devised and tested to maintain a desired
      polarization state (linear or circular) of the transmit beam for all pointing
      directions by means of rotating wave plates in the transmit and detection paths.
      Alternatively, the mirror coating can be optimized to preserve the linear
      polarization state of the transmitted beam. The compensation methods will enable
      ground-based scanning lidars to produce absolutely calibrated depolarization
      measurements.

PMID- 29047884
TI  - Optimization-based non-cooperative spacecraft pose estimation using stereo
      cameras during proximity operations.
AB  - Pose estimation for spacecraft is widely recognized as an important technology
      for space applications. Many space missions require accurate relative pose
      between the chaser and the target spacecraft. Stereo-vision is a usual mean to
      estimate the pose of non-cooperative targets during proximity operations.
      However, the uncertainty of stereo-vision measurement is still an outstanding
      issue that needs to be solved. With binocular structure and the geometric
      structure of the object, we present a robust pose estimation method for non
      cooperative spacecraft. Because the solar panel can provide strict geometry
      constraints, our approach takes the corner points of which as features. After
      stereo matching, an optimization-based method is proposed to estimate the
      relative pose between the two spacecraft. Simulation results show that our method
      improves the precision and robustness of pose estimation. Our system improves the
      performance with maximum 3D localization error less than 5% and relative rotation
      angle error less than 1 degrees . Our laboratory experiments further validate the
      method.

PMID- 29047885
TI  - Optimal design of depth-scaling error for multilayer diffractive optical elements
      with oblique incidence.
AB  - The mathematical analytic models of the relationship between depth-scaling error
      and diffraction efficiency/polychromatic integral diffraction efficiency (PIDE)
      for multilayer diffractive optical elements (MLDOEs) with oblique incidence are
      presented. A method for optimal design of the depth-scaling error for MLDOEs with
      consideration of comprehensive PIDE working within a range of incident angle is
      established. The effect of depth-scaling error on diffraction efficiency and PIDE
      of MLDOEs working in the visible wavelength with oblique incidence is analyzed.
      For the MLDOEs working within the range of incident angle 0-20 degrees , the
      maximum comprehensive PIDE is 98.24%, and the optimal relative depth-scaling
      error is -6.55%. The analytic method and conclusion provide a theoretical basis
      for the determination of manufacturing tolerance of depth-scaling error for
      MLDOEs with oblique incidence.

PMID- 29047886
TI  - Thermal conductivity of GaAs/AlAs distributed Bragg reflectors in semiconductor
      disk laser: comparison of molecular dynamics simulation and analytic methods.
AB  - GaAs/AlAs distributed Bragg reflectors (DBRs) are widely used in the gain chips
      of 1 MUm wave band semiconductor disk lasers (SDLs) as an end/folded cavity
      mirror. Because the generated redundant heat in the active region of a gain chip
      mainly dissipates through the DBR, thermal conductivities of DBRs are crucial for
      the output performance of SDLs. For the purpose of more reasonable semiconductor
      wafer design, to improve the thermal management of SDLs, accurate thermal
      conductivities of DBRs with various layer thicknesses are under considerable
      requirement. By the use of the equilibrium molecular dynamics (EMD) simulation
      and the Tersoff potential, thermal conductivities of GaAs/AlAs superlattices with
      different layer thickness are calculated, and computed results are compared with
      reported data to verify the validity of the EMD simulation. The computed thermal
      conductivities of GaAs/AlAs DBRs using the EMD method show significant reduction
      in contrast to the bulk value. Compared to EMD simulation, analytic methods
      result in smaller values of thermal conductivities and get close to the bulk
      value much more slowly with increasing layer thickness. In the layer thickness of
      interest (60-100 nm), the Matthiessen rule with alpha=1 for GaAs and alpha=0.5
      for AlAs is a practicable tool for thermal conductivity estimation.

PMID- 29047887
TI  - Topology-optimization-based design method of flexures for mounting the primary
      mirror of a large-aperture space telescope.
AB  - For the development of a large-aperture space telescope, one of the key
      techniques is the method for designing the flexures for mounting the primary
      mirror, as the flexures are the key components. In this paper, a topology
      optimization-based method for designing flexures is presented. The structural
      performances of the mirror system under multiple load conditions, including
      static gravity and thermal loads, as well as the dynamic vibration, are
      considered. The mirror surface shape error caused by gravity and the thermal
      effect is treated as the objective function, and the first-order natural
      frequency of the mirror structural system is taken as the constraint. The pattern
      repetition constraint is added, which can ensure symmetrical material
      distribution. The topology optimization model for flexure design is established.
      The substructuring method is also used to condense the degrees of freedom (DOF)
      of all the nodes of the mirror system, except for the nodes that are linked to
      the mounting flexures, to reduce the computation effort during the optimization
      iteration process. A potential optimized configuration is achieved by solving the
      optimization model and post-processing. A detailed shape optimization is
      subsequently conducted to optimize its dimension parameters. Our optimization
      method deduces new mounting structures that significantly enhance the optical
      performance of the mirror system compared to the traditional methods, which only
      focus on the parameters of existing structures. Design results demonstrate the
      effectiveness of the proposed optimization method.

PMID- 29047888
TI  - Realization of uniform and collimated light distribution in a single freeform
      Fresnel double surface LED lens.
AB  - In this work, a design method of a freeform-Fresnel composite surface lens is
      proposed, which can be applied on LED lighting optics to realize uniform and
      collimated light output in a single lens element. The lower lens surface is of
      freeform type, which transforms the light distribution from the LED sources to a
      uniform one, and the upper lens surface is of the Fresnel type, which further
      transforms the lights to a collimated beam. Through the optimization of lens
      parameters, the obtained lens has the advantages of compact volume, wide
      acceptance angle, high light extraction efficiency, and high design accuracy.

PMID- 29047889
TI  - Algorithm for the propagation of electromagnetic fields through etalons and
      crystals.
AB  - We investigate the propagation of general electromagnetic fields through optical
      layer structures made of either isotropic or anisotropic media, by using the
      spectrum-of-plane-waves analysis together with the S-matrix method. We also
      develop an algorithm based on the fast Fourier transform technique, with a
      numerically efficient sampling rule. By using this algorithm in combination with
      other system modeling techniques, we present a few simulation examples, such as
      field propagation through an isotropic Fabry-Perot etalon, as well as uniaxial
      crystal slabs with arbitrary orientation and optic axis direction.

PMID- 29047890
TI  - Weighted least-squares phase unwrapping algorithm based on a non-interfering
      image of an object.
AB  - Conventional quality maps for weighted least-squares phase unwrapping are not
      appropriate in regions of abnormal fringes. In this paper, the use of a non
      interfering image of an object for a reliability map is proposed for robust phase
      unwrapping. First, the conventional weighted least-squares algorithm is applied,
      and the unreliable region is detected. Then, the unreliable region is unwrapped
      iteratively using the non-interfering image of the object. Finally, both phase
      maps are combined and smoothed by a continuity operation. Experimental results
      show that the proposed algorithm is appropriate for unwrapping phase maps of
      abnormal fringes.

PMID- 29047891
TI  - Enhanced luminescence at 2.7  MUm of Na5Lu9F32 single crystals co-doped Er3+/Pr3+
      grown by Bridgman method.
AB  - Na5Lu9F32 single crystals co-doped with 1 mol. % Er3+ and various concentrations
      (0.1 mol. %, 0.3 mol. %, 0.5 mol. %, 0.7 mol. %, and 1 mol. %) of Pr3+ were
      successfully grown using the Bridgman method. Optical spectroscopic
      investigations of the obtained single crystal were reported for the absorption,
      emission, and luminous decay. The obtained single crystal appears with almost no
      absorption at the 2.7 MUm band, attributable to the OH- bond. According to the
      Judd-Ofelt (J-O) theory, the J-O intense parameters of Er3+ ions were calculated.
      Under the 980 nm LD pumping, an obviously enhanced emission at 2.7 MUm was
      obtained in the Er3+/Pr3+ co-doped crystal compared with the Er3+ singly doped
      crystal due to the energy transfer from Er3+ to Pr3+. The most intense emission
      at 2.7 MUm was obtained when the doping concentrations of Er3+ and Pr3+ were 1
      mol. % and 0.5 mol. % in the present research. The maximum emission cross-section
      and gain cross-section at 2.7 MUm were also estimated. Moreover, using the Dexter
      theory, the energy transfer microscopic parameters have been calculated, and the
      decay curve fitting using the Inokuti-Hirayama expression indicated the dipole
      dipole energy transfer from Er3+ to Pr3+ ions.

PMID- 29047892
TI  - Estimating constituents of optical isomers in mixed solution based on spin Hall
      effect of light.
AB  - In this paper, an optical method for precisely estimating constituents of optical
      isomers (OIs) in mixed solution is presented. We convert the composition ratio of
      OI into polarization-rotation-dependent spin Hall effect of light (SHEL). The
      theoretical model between the SHEL and OI composition ratio is established in the
      geometrical-optics picture, and the spatial shift can be measured through weak
      measurement technique. Based on our theory, the concentrations of glucose and
      fructose in a mixed solution are separately obtained. Our accurate measurements
      of the chiral enantiomer composition can provide an avenue for chiral drug
      synthesis and analysis.

PMID- 29047893
TI  - Experimental validation of nonlinearity suppression for an inverse-layer-type
      silicon photodiode and its prediction based on theoretical modeling.
AB  - The spectral nonlinearity of an inverse-layer-type silicon (Si) photodiode (PD)
      in the visible region was investigated. As expected by theoretical calculation,
      supralinearity and saturation of the Si PD, which are key factors of
      nonlinearity, were suppressed by applying a reverse voltage above 30 V.
      Experimentally observed nonlinear behavior depending on the reverse bias was
      compared to a theoretical model describing supralinearity, including the inner
      parameters of the Si PD, and these comparison results were in agreement. This
      theoretical model enables us to quantitatively predict the behavior of the
      supralinearity of the inverse-layer-type Si PD in various reverse bias
      conditions. Accurate experimental nonlinearity supported by theoretical
      predictions will contribute to high-accuracy optical measurement with the Si PD
      over a wide range of optical power levels and various reverse-bias voltages.

PMID- 29047894
TI  - Optical limiting performance of a GaAs/AlAs heterostructure microcavity in the
      near-infrared.
AB  - A multilayer GaAs/AlAs heterostructure forming a Fabry-Perot microcavity with a
      narrow resonance at 1.1 MUm was produced by molecular-beam epitaxy. Under
      nanosecond pulsed laser radiation, a blueshift of the resonant line, associated
      with a photo-induced negative change in refractive index in GaAs, was
      experimentally registered by using an optical parametric oscillator. The spectral
      shift was accompanied by a reduction in peak transmittance, associated with
      nonlinear intracavity absorption. Such a cavity can be used as an optical limiter
      at the resonant wavelength when both the spectral shift and the transmittance
      reduction contribute to the limiting effect. An exceptionally low limiting
      threshold of about 1  mJ/cm2 was observed in the experiment.

PMID- 29047895
TI  - Generation of perfect optical vortices using a Bessel-Gaussian beam diffracted by
      curved fork grating.
AB  - Perfect optical vortices (POVs) are beams whose topological charges are
      independent of radius, unlike conventional optical vortices. POVs are the Fourier
      transformation of Bessel-Gaussian (BG) beams and can be seen in the far-field
      diffraction of BG beams. In this paper, we present the generation of POVs of
      arbitrary charge using curved fork grating (CFG) illuminated by BG beam. For this
      purpose, first, a theoretical study of the Fresnel-Kirchhoff integral for
      diffraction of a BG beam by CFG is completed. The analytical results show the
      presence of vortex beams with various topological charges in diffraction orders.
      Then, diffraction of the BG beam with the order (l) by CFG with a topological
      charge (p) is numerically simulated. Additionally, experimental results prove the
      generation of POVs in diffraction orders. Also, experimental interference
      patterns obtained by interfering a POV and Gaussian beam confirm the ability of
      analytical solutions to determine the topological charges of vortex beams.
      Comparison of the results reveals the validity of the analytical, simulation, and
      experimental results.

PMID- 29047896
TI  - Multilayer-coated photodiode-based beam intensity monitor for polarization
      analysis of plasma soft X-ray laser.
AB  - A Mo/Si multilayer-coated photodiode detector (MP) for beam intensity monitoring
      was prototyped and characterized using synchrotron radiation and X-ray laser
      (XRL) sources in order to perform polarization analysis of a laser-driven plasma
      soft XRL generated from nickel-like silver plasma. At a wavelength of 13.9 nm and
      an angle of incidence of 45 degrees , the s-polarization reflectance is 0.525 and
      shows a strong positive correlation with the transmittance, corresponding to the
      photodiode current generated by the MP. We succeeded in performing polarization
      analysis of XRL beams with a large shot-to-shot intensity variation using the MP.
      Thus, this MP enables shot-to-shot monitoring and delivery of high intensity
      beams for downstream XRL experiments.

PMID- 29047897
TI  - Calibration of night vision goggles: an SI-units-based gain measurement
      technique.
AB  - A gain measurement technique for the calibration of night vision goggles (NVG) is
      proposed and evaluated. This technique is based on the radiance measurements at
      the input and output of the NVG. In contrast to the old definition, which uses a
      non-International System of Units (SI) traceable luminance, the "equivalent
      luminance unit," the suggested technique utilizes the radiance quantities that
      are traceable to the SI units through National Institute of Standards and
      Technology (NIST) standards. Due to the implementation of the scaling
      coefficients originating from the NVG spectral responsivities, the same NVG gain
      is expected within both techniques. The suggested method was evaluated at the
      NIST night vision calibration facility and the experimental data were compared to
      the results obtained with a commercial NVG test set. The comparison of the
      radiometric quantities obtained using the two different methods indicated
      differences up to 15% due to different calibration conditions. However, at proper
      calibration, equal NVG gains within both the suggested and old gain definitions
      were measured for the goggles equipped with a filmless image tube. The NVG gain
      uncertainty analysis, including the effect of no-moon night sky radiation, was
      performed for goggle types A, B, and C.

PMID- 29047898
TI  - Multiobjective optimization for a plasmonic nanoslit array sensor using Kriging
      models.
AB  - We propose an efficient multiobjective optimization approach for a plasmonic
      nanoslit array sensor using Kriging surrogate models. The universal Kriging
      models whose regression functions are zeroth-, first-, and second-order
      polynomials are adopted to estimate objective functions. The multiobjective
      extension of the genetic algorithm is used for Pareto optimal sensor geometry.
      The objective functions are the figure of merit defined as a ratio of peak
      wavelength shift at molecular adsorption and 3 dB bandwidth of transmission
      spectrum, and peak transmission power, respectively. The optical properties of a
      plasmonic slit sensor are investigated, such as transmission power, bandwidth,
      and peak shift, using the finite element method.

PMID- 29047899
TI  - UV-visible broadband wide-angle polarization-insensitive absorber based on metal
      groove structures with multiple depths.
AB  - A new periodic Al groove structure coated by SiO2 thin film is designed and
      numerically investigated for wide-angle and polarization-insensitive broadband
      absorption. A metal groove array presents optical absorption enhancement due to
      the cavity mode resonance, with the absorption peak capable of being shifted by
      controlling the depth of the metal groove. Broadband absorption can be realized
      by a periodic array of metal grooves with different depths combined in one single
      period. A two-dimensional Al structure with four different grooves in each period
      is designed to realize polarization-insensitive broadband absorption from 220 nm
      to 800 nm with average absorption efficiency over 80% within the incident angle
      of 40 degrees . These wide-angle and broadband absorption structures can be
      applied in UV/visible-related biochemical sensors, solar cells, or
      photocatalysts.

PMID- 29047900
TI  - Optimized design and fabrication of polymer/silica thermo-optic switch with low
      power consumption.
AB  - In this paper, the power-consumption characteristics of a polymeric thermo-optic
      (TO) switch consisting of a silica under-cladding on silicon substrate, a polymer
      core surrounded with polymer upper-cladding, and aluminum heating electrodes with
      different widths were investigated. Norland optical adhesive 73 with a larger TO
      coefficient was selected as the core layer, which could reduce the power
      consumption effectively. The silica under-cladding, with large thermal
      conductivity, could shorten the response time. The influences of the heating
      electrode width and the air trench structure on the power consumption of the
      device were systemically studied. A device with different widths of electrodes
      was fabricated by using conventional semiconductor fabrication techniques and
      measured with the planar optical waveguide testing system. Under 1550-nm
      wavelength, the power consumption of the device would be reduced from 23.27 to
      4.35 mW, while the heating electrode width was decreased from 25 to 7 MUm.
      Furthermore, it would be reduced to 1.7 mW after the air trench structure was
      employed. The switching time of the device was also measured, which was about 200
      MUs.

PMID- 29047901
TI  - Optical properties of a dichroic dye-doped liquid-crystal grating and its
      application to optical rotation measurement.
AB  - The diffraction properties of a twisted nematic liquid-crystal (TN-LC) grating,
      in which a dichroic dye was doped, were investigated experimentally in terms of
      the applicability to an optical system for determining the polarization angle of
      incident linearly polarized light. The main reason to dope a nematic LC material
      with a dichroic dye was to enhance the polarization dependence of the diffracted
      light intensities for the positive and negative first orders. We found the best
      values of the applied voltage for application in polarization angle measurement.
      The TN-LC grating with a high polarization sensibility was applied to the optical
      system for measuring the concentration of an optically active component in a
      liquid specimen. As a result, the applicability of the proposed optical system
      was revealed experimentally. Furthermore, the cause of the random measurement
      error is discussed briefly.

PMID- 29047902
TI  - Correcting groove error in gratings ruled on a 500-mm ruling engine using
      interferometric control.
AB  - Groove error is one of the most important factors affecting grating quality and
      spectral performance. To reduce groove error, we propose a new ruling-tool
      carriage system based on aerostatic guideways. We design a new blank carriage
      system with double piezoelectric actuators. We also propose a completely closed
      loop servo-control system with a new optical measurement system that can control
      the position of the diamond relative to the blank. To evaluate our proposed
      methods, we produced several gratings, including an echelle grating with 79 
      grooves/mm, a grating with 768  grooves/mm, and a high-density grating with 6000 
      grooves/mm. The results show that our methods effectively reduce groove error in
      ruled gratings.

PMID- 29047903
TI  - High-conversion-efficiency all-optical wavelength converter based on cascaded
      highly nonlinear fibers.
AB  - All-optical wavelength converters based on parametric processing of highly
      nonlinear fiber (HNLF) can provide low energy consumption, fast process speed,
      and modulation format agnosticism. A longer HNLF with a larger nonlinear
      coefficient and high pump power will contribute to achieve higher conversion
      efficiency. However, the injected pump power to the fiber is limited by its
      stimulated Brillouin scattering threshold, where longer fibers always have lower
      threshold powers. In the paper, we propose an all-optical wavelength converter
      with higher conversion efficiency by cascading two different HNLFs. We
      experimentally achieved -8  dB conversion efficiency and good converted signals
      with negligible power penalties.

PMID- 29047904
TI  - Cooperative execution of auto-focusing metrics in digital lensless holographic
      microscopy for internal-structured samples.
AB  - The cooperative execution of two metrics to automatically determine the best
      focal plane in digital lensless holographic microscopy (DLHM) is presented. This
      proposal is comprised of two stages: first, a quick coarse search over the whole
      reconstruction range by using Dubois's metric allows the finding of a range in
      which the best focal plane can be found. In a second stage, the modified enclosed
      energy (MEE) metric is used within the found range in the former stage to finely
      determine the best focal plane. While this cooperative implementation keeps the
      proven effectiveness of the MEE in DLHM, it reduces by at least 11 times the
      total computational complexity of the auto-focusing method with respect to the
      MEE method only. This proposal has been validated experimentally with DLHM
      holograms of a paramecium specimen, polystyrene beads, and the section of the
      head of a Drosophila melanogaster fly.

PMID- 29047905
TI  - Experimental optical encryption of grayscale information.
AB  - In this paper, we present a new protocol for achieving lower noise and
      consequently a higher dynamic range in optical encryption. This protocol allows
      for the securing and optimal recovery of any arbitrary grayscale images encrypted
      using an experimental double random phase mask encoding (DPRE) cryptosystem. The
      protocol takes advantage of recent advances that help reduce the noise due to the
      correlation of random phase mask in the decryption procedure and introduces the
      use of a "reference mask" as a reference object used to eliminate the noise due
      to the complex nature of the masks used in experimental DRPE setups. This noise
      reduction increases the dynamic range of the decrypted data, retaining the
      grayscale values to a higher extent and opening new possible applications. We
      detailed the procedure, and we present the experimental results, including an
      actual experimental video of a grayscale scene, confirming the validity of our
      proposal.

PMID- 29047906
TI  - Transfer matrix method for four-flux radiative transfer.
AB  - We develop a transfer matrix method for four-flux radiative transfer, which is
      ideally suited for studying transport through multiple scattering layers. The
      model predicts the specular and diffuse reflection and transmission of multilayer
      composite films, including interface reflections, for diffuse or collimated
      incidence. For spherical particles in the diffusion approximation, we derive
      closed-form expressions for the matrix coefficients and show remarkable agreement
      with numerical Monte Carlo simulations for a range of absorption values and film
      thicknesses, and for an example multilayer slab.

PMID- 29047907
TI  - All-fiber multimode interferometer for the generation of a switchable multi
      wavelength thulium-doped fiber laser.
AB  - A compact all-fiber multimode interferometer (MMI) designed to produce a
      switchable multi-wavelength thulium-doped fiber laser (TDFL) is proposed and
      demonstrated. The TDFL fiber ring cavity employs a 60-cm-long multimode fiber
      into the cavity to induce multimode interference and provide intensity-dependent
      loss in order to generate a multi-wavelength output. The suppression of mode
      competition and the overall stability of the TDFL are further improved by
      exploiting the filtering capability of a Sagnac loop. By increasing the pump
      power, a switchable wavelength output is allowed with a wavelength spacing of
      ~1.8  nm. At 361 mW input pump power, nine laser lines are generated, with a
      maximum signal-to-noise ratio value of ~36  dB and an output power of 3.3 mW. The
      multi-wavelength TDFL also exhibits great stability in one-hour operation with a
      wavelength drift of 0.2 nm. The proposed multi-wavelength TDFL has potential to
      be employed in future thulium-doped fiber amplifier-based telecommunication
      infrastructure and also may be applicable in areas such as sensing and
      spectroscopy, largely associated with its 2 MUm wavelength output.

PMID- 29047909
TI  - Fiber-integrated spectroscopy device for hot alkali vapor.
AB  - We introduce an all-glass, vacuum tight, fiber-integrated and alkali compatible
      spectroscopy device consisting of two conventional optical fibers spliced to each
      end of a capillary. This is mainly realized through a decentered splicing method
      allowing refilling of the capillary and controlling the vapor density inside. We
      analyze the light guidance of the setup through simulations and measurements of
      the transmission efficiency at different wavelengths and show that filling it
      with highly reactive alkali metals is possible, and that the vapor density can be
      controlled reliably.

PMID- 29047910
TI  - Fast lithographic source optimization using a batch-processing sequential least
      square estimator.
AB  - This paper proposes a fast source optimization (SO) method for lithography
      systems to improve the imaging performance of different hotspots on the fullchip
      layout. Hotspots are referred to as the critical locations on the layout that are
      difficult to print. A fullchip layout usually includes numerous hotspots with
      different geometric characteristics. Current SO approaches collect all of the
      data from different hotspots before the optimization, and then try to calculate
      the common optimal source for all hotspots. If any new data from unaccounted
      hotspots become available, the optimal source has to be recalculated. This paper
      first develops a batch-processing sequential least square estimator, and then
      uses it to iteratively modify the source pattern based on the ongoing hotspot
      data. The optimized source for one hotspot can be updated to suit others without
      redundant computation. Simulations show that the proposed method can
      significantly accelerate the SO procedure, while improving the imaging
      performance of multiple hotspots.

PMID- 29047908
TI  - Composite infrared spectrometer (CIRS) on Cassini: publisher's note.
AB  - This publisher's note renumbers the reference list in Appl. Opt.56, 5274
      (2017)APOPAI0003-693510.1364/AO.56.005274.

PMID- 29047911
TI  - Magnetically tunable enhanced absorption of circularly polarized light in
      graphene-based 1D photonic crystals.
AB  - We theoretically investigate the magnetic-field-induced terahertz absorption
      enhancement of a graphene-based one-dimensional photonic crystal using the 4*4
      transfer matrix method for the circular polarization of light. The results show
      that the magnetically tunable absorption of the structure depends on the circular
      polarization state, magnetic circular dichroism, and, interestingly, absorption
      behaviors of right-handed and left-handed circularly polarized light interchange
      by changing the direction of the magnetic field. These properties can be used to
      design the circular-polarization-based sensors.

PMID- 29047912
TI  - Confocal signal evaluation algorithms for surface metrology: uncertainty and
      numerical efficiency.
AB  - Confocal microscopy is one of the dominating measurement techniques in surface
      metrology, with an enhanced lateral resolution compared to alternative optical
      methods. However, the axial resolution in confocal microscopy is strongly
      dependent on the accuracy of signal evaluation algorithms, which are limited by
      random noise. Here, we discuss the influence of various noise sources on confocal
      intensity signal evaluating algorithms, including center-of-mass, parabolic least
      square fit, and cross-correlation-based methods. We derive results in closed form
      for the uncertainty in height evaluation on surface microstructures, also
      accounting for the number of axially measured intensity values and a threshold
      that is commonly applied before signal evaluation. The validity of our results is
      verified by numerical Monte Carlo simulations. In addition, we implemented all
      three algorithms and analyzed their numerical efficiency. Our results can serve
      as guidance for a suitable choice of measurement parameters in confocal surface
      topography measurement, and thus lead to a shorter measurement time in practical
      applications.

PMID- 29047913
TI  - Reduction of far off-resonance laser frequency drifts based on the second
      harmonic of electro-optic modulator detection in the optically pumped
      magnetometer.
AB  - The frequency drifts of the probe laser could be coupled into the calibrated
      scale factor of the optically pumped magnetometer (OPM) and induce an error of
      the measurement accuracy. We propose a method to reduce the far off-resonance
      laser frequency drifts based on the second harmonic of the electro-optic
      modulator (EOM) detection system in the all-optical K-Rb hybrid pumping
      magnetometer. Adopting the closed-loop feedback by monitoring the second-harmonic
      component in real time, the frequency drift of the probe laser has been
      effectively reduced by about five times to ~30  MHz/0.5  h at the detuning of 130
      GHz and the cell temperature of 443 K. Besides, this technique has been
      demonstrated to be helpful for reducing the frequency drifts at different
      detuning points and temperatures. This method is not only suitable for the
      development of more compact, high-sensitivity OPMs due to the long-term stability
      improvement with no extra optical path, but also can be applied to other atomic
      devices and EOM detection systems for reducing the influence of the laser.

PMID- 29047914
TI  - Image quality and spectral performance evaluations of a polarization imaging
      spectrometer based on a Savart polariscope.
AB  - The modulation transfer function (MTF) and signal-to-noise ratio (SNR) are the
      key parameters to evaluate quantitatively the image quality and spectral
      performance in a polarization imaging spectrometer based on a Savart polariscope.
      In order to evaluate the image quality and reflect the detecting ability of the
      imaging spectrometer, calibration experiments on the MTF, SNR, and spectral
      resolution were carried out and some important conclusions were obtained. For
      incident radiance values 4.464, 3.119, and 0.523  w/m2.sr, the average SNRs of
      the interferogram were 500, 400, and 200 dB, respectively, and the MTF is 0.24.
      During the spectral resolution calibration, the maximum optical path difference
      was set as 57.08 um, and the measured value is greater than the theoretical
      value, which is mainly caused by the structural design of the polarization
      imaging spectrometer. For the wavelength range of [500 nm, 600 nm], the SNR of
      the spectrum is lower and about 50 dB, while the SNR is obviously higher in a
      range of lambda?[600 nm, 960 nm]. This study provides a theoretical and practical
      guidance for improving the image quality and judging the spectral performance of
      the polarization imaging spectrometer.

PMID- 29047915
TI  - Calculation of nonlinearly deformed membrane shape of liquid lens caused by
      uniform pressure.
AB  - The paper discusses a numerical calculation of deformation of a circular
      axisymmetric membrane of a liquid lens caused by the pressure of an optical
      liquid. Since such deflections of the membrane are many times larger than the
      membrane thickness, a nonlinear model is applied and generalized relationships
      are derived that characterize the resulting shape with a high precision and
      permit an accurate analysis of imaging properties of the lens and of optical
      aberrations. By comparison with experimental data, it is shown that the presented
      model is suitable to describe the deformation of the membrane of the lens.

PMID- 29047916
TI  - Optical mapping of prefrontal activity in pathological gamblers.
AB  - Functional near-infrared spectroscopy (fNIRS) has emerged as a highly promising
      brain mapping technique that enables continuously and noninvasively monitoring
      the hemodynamic responses in the human brain. In this study, fNIRS was utilized
      to identify the different brain activation patterns between pathological gamblers
      (PGs) and healthy controls (HCs). Specifically, we examined the hemodynamic
      changes in the prefrontal cortex using fNIRS recordings during the completion of
      executive function and decision-making tasks for both PGs and HCs. Our mapping
      results revealed that PGs and HCs exhibited notable differences in the
      hemodynamic responses and brain activation patterns across the prefrontal region.

PMID- 29047917
TI  - Shape measurement with modified phase-shift lateral shearing interferometry
      illumination and radial basis function.
AB  - Three-dimensional shapes of objects were evaluated with modified phase-shift
      lateral shearing interferometry illumination and radial basis function. A simple
      optical system was developed to create the fringe pattern based on the Murty
      interferometer. The phase shift was generated only by moving a plane-parallel
      plate along an in-plane parallel direction. A novel moving radial basis function
      method was presented to improve the quality of fringe patterns. And the proper
      calculation window size was given based on numerical simulation. Three
      dimensional shapes of two kinds of objects were determined to verify the
      feasibility and effectiveness of the proposed method, and the reconstructed
      height distributions were in good accordance with the referenced data.

PMID- 29047918
TI  - Star tracking method based on multiexposure imaging for intensified star
      trackers.
AB  - The requirements for the dynamic performance of star trackers are rapidly
      increasing with the development of space exploration technologies. However,
      insufficient knowledge of the angular acceleration has largely decreased the
      performance of the existing star tracking methods, and star trackers may even
      fail to track under highly dynamic conditions. This study proposes a star
      tracking method based on multiexposure imaging for intensified star trackers. The
      accurate estimation model of the complete motion parameters, including the
      angular velocity and angular acceleration, is established according to the
      working characteristic of multiexposure imaging. The estimation of the complete
      motion parameters is utilized to generate the predictive star image accurately.
      Therefore, the correct matching and tracking between stars in the real and
      predictive star images can be reliably accomplished under highly dynamic
      conditions. Simulations with specific dynamic conditions are conducted to verify
      the feasibility and effectiveness of the proposed method. Experiments with real
      starry night sky observation are also conducted for further verification.
      Simulations and experiments demonstrate that the proposed method is effective and
      shows excellent performance under highly dynamic conditions.

PMID- 29047919
TI  - Response non-uniformity of beam profiling cameras at near-infrared laser
      wavelengths.
AB  - The response non-uniformities of laser beam profiling cameras were investigated
      experimentally at near-infrared laser wavelengths. A uniform-irradiance light
      source with near-infrared laser wavelengths, and also a visible wavelength as
      comparison, was constructed for testing several different commercially available
      beam profiling cameras. The response signals of all charge-coupled device (CCD)
      type sensors showed a strong dependence on the irradiant wavelength. The pixel-to
      pixel non-uniformity of CCDs at 1064 nm increased rapidly with the reduction of
      exposure time, whereas that of CMOS sensors was maintained independently of these
      parameters. The characteristics of CCDs were discussed in terms of charge leakage
      effect, which is a likely source of these phenomena.

PMID- 29047920
TI  - All-fiber wavelength-tunable Tm-doped fiber laser mode locked by SESAM with 120 
      nm tuning range.
AB  - We demonstrate an all-fiber widely wavelength-tunable thulium-doped fiber laser
      (TDFL) mode locked by a semiconductor saturable absorber mirror (SESAM). The
      tuning range spans 121 nm, from 1862 nm to 1983 nm. The central wavelength is
      tuned by a grating-based tunable filter in the ring laser cavity. To the best of
      our knowledge, this is so far the most widely wavelength-tunable TDFL mode locked
      by SESAM.

PMID- 29047921
TI  - Game theory-based visual tracking approach focusing on color and texture
      features.
AB  - It is difficult for a single-feature tracking algorithm to achieve strong
      robustness under a complex environment. To solve this problem, we proposed a
      multifeature fusion tracking algorithm that is based on game theory. By focusing
      on color and texture features as two gamers, this algorithm accomplishes tracking
      by using a mean shift iterative formula to search for the Nash equilibrium of the
      game. The contribution of different features is always keeping the state of
      optical balance, so that the algorithm can fully take advantage of feature
      fusion. According to the experiment results, this algorithm proves to possess
      good performance, especially under the condition of scene variation, target
      occlusion, and similar interference.

PMID- 29047922
TI  - Measurement method of high spectral resolution lidar with a multimode laser and a
      scanning Mach-Zehnder interferometer.
AB  - A simple high spectral resolution lidar technique using a multi-longitudinal mode
      laser is proposed for measuring aerosol extinction and backscattering
      coefficients. A scanning interferometer having the same free spectral range as
      the mode spacing of the laser is used to separate Rayleigh from Mie scattering.
      Scanning the interferometer in the span of one fringe, the lidar signals at the
      minimum and maximum Mie-scattering transmission are measured. The Rayleigh
      scattering signal is analyzed from these signals, and the aerosol extinction
      coefficient is derived. The interferometer transmittance for Mie scattering is
      calibrated with the reference signals taken with a portion of the transmitted
      laser beam.

PMID- 29047923
TI  - Simple and flexible phase compensation for digital holographic microscopy with
      electrically tunable lens.
AB  - In a digital holographic microscopy (DHM) system, different microscope objectives
      (MOs) will introduce different phase distortions and thus lead to measurement
      errors. To address this problem, we present a simple and flexible method to
      compensate all phase distortions by introducing an electrically tunable lens
      (ETL) in the reference arm for a DHM system with multiple MOs. By exactly
      controlling the external currents of the ETL, we can change the reference wave
      front to match the wave front introduced by different MOs without complex
      alignment or additional numerical postprocessing manipulations. This method is
      suitable for quantitative real-time phase imaging especially when it refers to
      multiple MOs. To demonstrate the validity and effectiveness of our scheme, we did
      a series of simulations and carried out some real experiments with two different
      MOs (4* and 10*).

PMID- 29047924
TI  - Temperature dependence of photoemission characteristics from AlxGa1-xAs/GaAs
      photocathodes.
AB  - In this work, photon-enhanced thermionic emission (PETE), which simultaneously
      harvests solar photonic and thermionic energies, is studied theoretically and
      experimentally with a transmission-mode AlxGa1-xAs/GaAs cathode within a compact
      photodiode. The effect of temperature on energy distribution and photoemission
      yield was experimentally studied in the wavelength range 450-850 nm. The
      variation of the energy distribution with increasing temperatures demonstrates
      that direct photoemission gradually declines, while PETE contribution increases
      with increased heat. Further quantitative proof of the PETE phenomenon can be
      observed at 850 nm, as temperature increases from 20 degrees C to 90 degrees C.
      The PETE model with the t-mode AlxGa1-xAs/GaAs cathode is deduced, and the
      temperature dependence of electron affinity can be achieved. The results show
      promising applications of the AlxGa1-xAs/GaAs cathode in combined solar/thermal
      energy conversion.

PMID- 29047925
TI  - Tunable graphene-based plasmonic multispectral and narrowband perfect
      metamaterial absorbers at the mid-infrared region.
AB  - We numerically investigate the optical performance of a periodically patterned H
      shaped graphene array by the finite-difference time-domain (FDTD) in the mid
      infrared region. The simulated results reveal that absorption spectra of the
      proposed structure consist of two dramatic narrowband perfect absorption peaks
      located at 6.3 MUm (Mode 1) and 8.6 MUm (Mode 2) with high absorption
      coefficients of 99.65% and 99.80%, respectively. Two impressive absorption
      bandwidths that are the full width at half-maximum (FWHM) of the resonant
      frequency of 90 nm and 188 nm are obtained. The dipole resonance mode is
      supported by graphene ribbon at a wavelength of 6.3 MUm. While the other
      absorption, attributed to the hybridized mode, is a new resonance that is
      different from the dipole resonance. The spectral position of the absorption
      peaks can be dynamically tuned by controlling the refractive index of the
      dielectric and the Fermi energy of graphene. Furthermore, we can obtain
      multispectral absorption peaks by applying multilayer graphene arrays. These
      design approaches enable us to control the number of absorption spectra and such
      absorbers will benefit the easy-to-fabricate nanophotonic devices for optical
      filtering, thermal detectors, and electromagnetic wave energy storage.

PMID- 29047926
TI  - Effects of elemental images' quantity on three-dimensional segmentation using
      computational integral imaging: publisher's note.
AB  - This publisher's note corrects the Funding section in Appl. Opt.56, 2132
      (2017)APOPAI0003-693510.1364/AO.56.002132.

PMID- 29047927
TI  - Fiber-coupled, UV-SWIR hyperspectral imaging sensor for combustion diagnostics.
AB  - A fiber-coupled, hyperspectral imaging sensor (HSIS) ranging from ultraviolet
      (UV) to short-wavelength-infrared (SWIR) wavelengths is developed for remote
      detection of planar [two-dimensional (2D)], spectrally resolved flame emission.
      The key component of the sensor is a dimension-reduction 2D-to-1D (one
      dimensional) fiber-optic array that contains 1024 fibers and features high-UV
      optical transmission (>30% transmission at 310-340 nm, >90% at 340-2000 nm), wide
      operational wavelengths (300-2400 nm), and a compact and robust design (full
      length <5  cm). The flame-emission signals are transmitted to the remote HSIS
      through a 3-m-long, UV-grade, imaging fiber bundle that consists of 30,000 single
      mode fibers. The design of the 2D-to-1D fiber array, the fiber-characterization
      process, and the sensor development are discussed in detail. 2D spectrally
      resolved measurements of CH*, OH*, and C2* distribution are made in premixed
      laminar flames. Improved chemiluminescence-based fuel/air ratio measurements
      using spectrally resolved detection are demonstrated. The results of the current
      study indicate that implementation of fiber-coupled HSIS is feasible in practical
      gas-turbine-engine test facilities with limited optical access.

PMID- 29047928
TI  - Improved laser-based triangulation sensor with enhanced range and resolution
      through adaptive optics-based active beam control.
AB  - Various existing target ranging techniques are limited in terms of the dynamic
      range of operation and measurement resolution. These limitations arise as a
      result of a particular measurement methodology, the finite processing capability
      of the hardware components deployed within the sensor module, and the medium
      through which the target is viewed. Generally, improving the sensor range
      adversely affects its resolution and vice versa. Often, a distance sensor is
      designed for an optimal range/resolution setting depending on its intended
      application. Optical triangulation is broadly classified as a spatial-signal
      processing-based ranging technique and measures target distance from the location
      of the reflected spot on a position sensitive detector (PSD). In most
      triangulation sensors that use lasers as a light source, beam divergence-which
      severely affects sensor measurement range-is often ignored in calculations. In
      this paper, we first discuss in detail the limitations to ranging imposed by beam
      divergence, which, in effect, sets the sensor dynamic range. Next, we show how
      the resolution of laser-based triangulation sensors is limited by the interpixel
      pitch of a finite-sized PSD. In this paper, through the use of tunable focus
      lenses (TFLs), we propose a novel design of a triangulation-based optical
      rangefinder that improves both the sensor resolution and its dynamic range
      through adaptive electronic control of beam propagation parameters. We present
      the theory and operation of the proposed sensor and clearly demonstrate a range
      and resolution improvement with the use of TFLs. Experimental results in support
      of our claims are shown to be in strong agreement with theory.

PMID- 29047929
TI  - Finite element simulation of light transfer in turbid media under structured
      illumination.
AB  - The spatial-frequency domain (SFD) imaging technique allows us to estimate the
      optical properties of biological tissues in a wide field of view. The technique
      is, however, prone to error in measurement because the two crucial assumptions
      used for deriving the analytical solution to the diffusion approximation cannot
      be met perfectly in practical applications. This research mainly focused on
      modeling light transfer in turbid media under the normal incidence of structured
      illumination using the finite element method (FEM). Finite element simulations
      were performed for 50 simulation samples with different combinations of optical
      absorption and scattering coefficients for varying spatial frequencies, and the
      results were then compared with the analytical method and Monte Carlo simulation.
      Relationships between diffuse reflectance and dimensionless absorption and
      dimensionless scattering coefficients were investigated. The results indicated
      that the FEM provided reasonable results for diffuse reflectance, compared with
      the analytical method. Both the FEM and the analytical method overestimated the
      reflectance for MUtr/fx values of greater than 2 and underestimated the
      reflectance for MUtr/fx values of smaller than 2. Larger values of MUs'/MUa
      yielded better diffuse reflectance estimations than did those of smaller than 10.
      The reflectance increased nonlinearly with the dimensionless scattering, whereas
      the reflectance decreased linearly with the dimensionless absorption. It was also
      observed that diffuse reflectance was relatively stable and insensitive to MUs'
      when the dimensionless scattering was larger than 50. Overall results demonstrate
      that the FEM is effective for modeling light transfer in turbid media and can be
      used to explore the effects of crucial parameters for the SFD imaging technique.

PMID- 29047930
TI  - Heat-coupled Gaussian continuous-wave double-pass optical parametric oscillator:
      thermally induced phase mismatching for periodically poled MgO:LiNbO3 crystal.
AB  - In this paper, a model describing the thermal effects on the optical parametric
      oscillator (OPO) of Gaussian continuous waves in double-pass cavities is
      presented. Eight equations, including forward and backward nonlinear waves, heat,
      and thermally induced phase mismatching equations, were coupled and solved
      simultaneously to investigate the effect of heat generation on the OPO's
      efficiency. The model was applied for a periodically poled MgO:LiNbO3 crystal
      with an excellent agreement with experimental data. The numerical calculations
      have been carried out by a homemade code written in Intel FORTRAN, which used a
      finite difference method.

PMID- 29047931
TI  - Black phosphorus flakes covered microfiber for Q-switched ytterbium-doped fiber
      laser.
AB  - We demonstrate a passively Q-switched ytterbium-doped fiber laser based on black
      phosphorus (BP) flakes covered microfiber. The BP saturable absorber is
      fabricated by sandwiching a microfiber between two pieces of polydimethylsiloxane
      supported BP flakes film, which is prepared by the mechanical exfoliation method.
      In this case the BP flakes can be well protected from the action of air and
      moisture. By incorporating BP flakes covered microfiber into a ytterbium-doped
      ring fiber laser, stable and reliable Q-switched operation at 1064 nm can be
      realized via interaction between few-layers BP flakes and the evanescent field of
      the laser. The laser allows Q-switched pulse generation with a repetition rate in
      the range of 26-76 kHz and a pulse duration in the range of 5.5-2.0 MUs, by
      varying the pump power from 38 mW to 100 mW.

PMID- 29047932
TI  - Performance analysis of a PPM-FSO communication system with an avalanche
      photodiode receiver over atmospheric turbulence channels with aperture averaging.
AB  - The average bit error rate (ABER) performance of an avalanche-photodiode (APD)
      based pulse-position modulation (PPM) free-space optical (FSO) communication
      system is investigated considering the aperture averaging effect. The approximate
      ABER expression is theoretically derived in terms of M and exponentiated Weibull
      (EW) distributions under weak-to-strong turbulent atmosphere conditions with a
      binary PPM (BPPM) scheme. Union-bound and Hermite polynomials are then considered
      to estimate the performance of M-ary PPM FSO systems. The system performance is
      analyzed with the aperture sizes, turbulence strengths, receiver temperatures,
      and average photon counts taken into account. The results show that an optimal
      average APD gain, which is affected by receiver temperature, can be chosen to
      minimize the ABER value. And the impact of aperture averaging on the system
      performance over M distribution is not so apparent as that over EW distribution
      for different temperatures, turbulent strengths, and average photon counts. In
      addition, the present APD-based system can offer better ABER performance than
      that of a P-i-N-based PPM system over both EW and M fading channels at 300 and
      500 K. This work is beneficial to the FSO system design.

PMID- 29047933
TI  - Lidar algorithms for atmospheric slant range visibility, meteorological
      conditions detection, and atmospheric layering measurements.
AB  - Visibility at airports has to do, in many ways, with flight and ground safety. We
      present a novel method and algorithms based on lidar measurements and signal
      noise subtraction to provide atmospheric layering and estimated visibility values
      for tower controllers and meteorologists as well as from the pilot's point of
      view, according to the International Civil Aviation Organization and World
      Meteorological Organization requirements.

PMID- 29047934
TI  - Lensless photography with only an image sensor.
AB  - Photography usually requires optics in conjunction with a recording device (an
      image sensor). Eliminating the optics could lead to new form factors for cameras.
      Here, we report a simple demonstration of imaging using a bare CMOS sensor that
      utilizes computation. The technique relies on the space variant point-spread
      functions resulting from the interaction of a point source in the field of view
      with the image sensor. These space-variant point-spread functions are combined
      with a reconstruction algorithm in order to image simple objects displayed on a
      discrete LED array as well as on an LCD screen. We extended the approach to video
      imaging. Finally, we performed experiments to analyze the parametric impact of
      the object distance. Improving the sensor designs and reconstruction algorithms
      can lead to useful cameras without optics.

PMID- 29047935
TI  - Measurement of picometer-scale mirror dynamics.
AB  - A high-speed interferometer has been designed and built to measure the dynamics
      of the James Webb Space Telescope primary mirror system currently under testing.
      This interferometer is capable of tracking large absolute motion (i.e., piston)
      of the mirror's entire surface over orders of magnitudes of wavelengths
      displacement. Preliminary tests have shown it to be capable of measuring dynamic
      effects on the level of tens of picometers reliably. This paper reports the
      details of test setup to do so, the data system used to collect and process the
      data, and the algorithms to distill the dynamics motions detected. The results
      that were obtained are presented and followed by a discussion of the conclusions
      and potential applications of this measurement technique.

PMID- 29047936
TI  - Centroid estimation for a Shack-Hartmann wavefront sensor based on stream
      processing.
AB  - Using center of gravity to estimate the centroid of the spot in a Shack-Hartmann
      wavefront sensor, the measurement corrupts with photon and detector noise.
      Parameters, like window size, often require careful optimization to balance the
      noise error, dynamic range, and linearity of the response coefficient under
      different photon flux. It also needs to be substituted by the correlation method
      for extended sources. We propose a centroid estimator based on stream processing,
      where the center of gravity calculation window floats with the incoming pixel
      from the detector. In comparison with conventional methods, we show that the
      proposed estimator simplifies the choice of optimized parameters, provides a unit
      linear coefficient response, and reduces the influence of background and noise.
      It is shown that the stream-based centroid estimator also works well for limited
      size extended sources. A hardware implementation of the proposed estimator is
      discussed.

PMID- 29047937
TI  - Simple light-emitting electrochemical cell using reduced graphene oxide and a
      ruthenium (II) complex.
AB  - We report the use of conducting substrates from reduced graphene oxide (rGO)
      applied in light-emitting electrochemical cells (LECs) in which we used an
      electroluminescent polymer as a light-emitting layer. The emitting layer was
      composed of an organic metal complex of tris(2, 2'-bipyridine) ruthenium (II)
      linked to the sodium tetrafluoroborate anion ([Ru(bpy)3]+2)(BF4)-1. The luminance
      generated from the electroluminescent device was 6.89  Cd/m2 when applying a
      voltage of 13.48 V and a current of 10.19 mA. The luminance of this device was
      kept on almost constant for 36.84 min. The prolonged lifetime of the
      electrochemical device was achieved by depositing an rGO thin layer with a 161.3
      nm thickness inside the LEC structure.

PMID- 29047938
TI  - Fast lithography aerial image calculation method based on machine learning.
AB  - Aerial image calculation for thick masks is an indispensable but time-consuming
      step in most lithography simulations. This paper develops a fast thick-mask
      aerial image calculation method based on machine learning for partially coherent
      lithography systems. First, some sparse sampling points are chosen from the
      source plane to represent the partially coherent illumination. Then, the training
      libraries of thick-mask diffraction near-fields are built up for all sampling
      points based on a set of representative mask features. For an arbitrary thick
      mask, we calculate its aerial image using the nonparametric kernel regression
      technique and the pre-calculated training libraries. Subsequently, a post
      processing method is applied to compensate for the estimation error and improve
      the computational accuracy. In addition, this paper also studies the impacts of
      several key factors on the accuracy and efficiency of the proposed method.
      Finally, the proposed method is verified by the simulations at 45 nm and 14 nm
      technology nodes.

PMID- 29047939
TI  - Optical, magnetic, and charge-carriers transport properties of a transition
      metal: bulk palladium.
AB  - Three parametric models of Drude-Lorentz (DL) are used to describe the spectral
      variation of the dielectric function of bulk palladium. An improved version of
      the acceptance-probability-controlled simulated annealing method is applied to
      optimize the values of the parameters involved in the models: high-frequency
      dielectric constant, free-electron collision frequency and corresponding
      relaxation time, oscillation strengths, nominal resonance frequencies, and
      Lorentzian widths. Normalization of the oscillation strengths allows the
      introduction of a new parameter in the context of the original DL model: the
      number density ratio, which is the ratio between the number density of conduction
      electrons and the number density of metal atoms. Inclusion of this parameter in
      the optimization procedure allows us to evaluate additional parameters related to
      the charge-carriers transport: the number density of conduction electrons,
      average effective mass of conduction electrons and holes, Fermi energy and
      electronic density of states at the Fermi energy, electrical resistivity,
      intrinsic mean-free path of conduction electrons, electronic heat capacity, Hall
      coefficient, as well as the mobilities of conduction electrons and holes. The
      paramagnetic and diamagnetic susceptibilities are also included as derived
      parameters. A parametric form of the bulk Pd dielectric function, with
      incorporation of the average local electric field effect in the Lorentz
      contribution, is reported.

PMID- 29047940
TI  - Experimental analysis of the dynamic north-finding method based on a fiber optic
      gyroscope.
AB  - This paper demonstrates the principles of static and dynamic north-finding
      methods by measuring the projection of the Earth's rotation rate with a fiber
      optic gyroscope. For a comprehensive comparison of the two methods, the influence
      of a closed-loop feedback mechanism of a servo motor in a turntable is taken into
      consideration. Thus, we proposed the static and dynamic north-finding
      experimental implementations according to the different impact of the motor
      jitters and the different seeking times. Experimental results show that the
      dynamic method can reduce the north-finding bias error and instability by 60.1%
      and 54.6%, respectively, in the seeking time of 360 s, while the reduced
      proportions are 81.3% and 82.5%, respectively, in the seeking time of 120 s,
      compared with the static method under the jittering effect of the turntable.
      Therefore, it can be concluded that the dynamic method is more accurate and
      robust to the jittering effect.

PMID- 29047941
TI  - Design and characterization of an integrated surface ion trap and micromirror
      optical cavity.
AB  - We have fabricated and characterized laser-ablated micromirrors on fused silica
      substrates for constructing stable Fabry-Perot optical cavities. We highlight
      several design features which allow these cavities to have lengths in the 250-300
      MUm range and be integrated directly with surface ion traps. We present a method
      to calculate the optical mode shape and losses of these micromirror cavities as
      functions of cavity length and mirror shape, and confirm that our simulation
      model is in good agreement with experimental measurements of the intracavity
      optical mode at a test wavelength of 780 nm. We have designed and tested a
      mechanical setup for dampening vibrations and stabilizing the cavity length, and
      explore applications for these cavities as efficient single-photon sources when
      combined with trapped Yb171+ ions.

PMID- 29047942
TI  - Classification of morphologically similar algae and cyanobacteria using Mueller
      matrix imaging and convolutional neural networks.
AB  - We present the Mueller matrix imaging system to classify morphologically similar
      algae based on convolutional neural networks (CNNs). The algae and cyanobacteria
      data set contains 10,463 Mueller matrices from eight species of algae and one
      species of cyanobacteria, belonging to four phyla, the shapes of which are mostly
      randomly oriented spheres, ovals, wheels, or rods. The CNN serves as an automatic
      machine with learning ability to help in extracting features from the Mueller
      matrix, and trains a classifier to achieve a 97% classification accuracy. We
      compare the performance in two ways. One way is to compare the performance of
      five CNNs that differ in the number of convolution layers as well as the
      classical principle component analysis (PCA) plus the support vector machine
      (SVM) method; the other way is to quantify the differences of scores between full
      Mueller matrix and the first matrix element m11, which does not contain
      polarization information under the same conditions. As the results show, deeper
      CNNs perform better, the best of which outperforms the conventional PCA plus SVM
      method by 19.66% in accuracy, and using the full Mueller matrix earns 6.56%
      increase of accuracy than using m11. It demonstrates that the coupling of Mueller
      matrix imaging and CNN may be a promising and efficient solution for the
      automatic classification of morphologically similar algae.

PMID- 29047943
TI  - Feasibility study of a space-based high pulse energy 2  MUm CO2 IPDA lidar.
AB  - Sustained high-quality column carbon dioxide (CO2) atmospheric measurements from
      space are required to improve estimates of regional and continental-scale sources
      and sinks of CO2. Modeling of a space-based 2 MUm, high pulse energy, triple
      pulse, direct detection integrated path differential absorption (IPDA) lidar was
      conducted to demonstrate CO2 measurement capability and to evaluate random and
      systematic errors. Parameters based on recent technology developments in the 2
      MUm laser and state-of-the-art HgCdTe (MCT) electron-initiated avalanche
      photodiode (e-APD) detection system were incorporated in this model. Strong
      absorption features of CO2 in the 2 MUm region, which allows optimum lower
      tropospheric and near surface measurements, were used to project simultaneous
      measurements using two independent altitude-dependent weighting functions with
      the triple-pulse IPDA. Analysis of measurements over a variety of atmospheric and
      aerosol models using a variety of Earth's surface target and aerosol loading
      conditions were conducted. Water vapor (H2O) influences on CO2 measurements were
      assessed, including molecular interference, dry-air estimate, and line
      broadening. Projected performance shows a <0.35  ppm precision and a <0.3  ppm
      bias in low-tropospheric weighted measurements related to column CO2 optical
      depth for the space-based IPDA using 10 s signal averaging over the Railroad
      Valley (RRV) reference surface under clear and thin cloud conditions.

PMID- 29047944
TI  - Long-term (2007-2013) analysis of aerosol optical properties over four locations
      in the Indo-Gangetic plains: erratum.
AB  - The authors regret the incomplete acknowledgment in Appl. Opt.55, 6199
      (2016)APOPAI0003-693510.1364/AO.55.006199.

PMID- 29047945
TI  - Color-image reconstruction for two-wavelength digital holography using a
      generalized phase-shifting approach.
AB  - We propose a color-image reconstruction method for two-wavelength digital
      holography using generalized phase-shifting digital holography (GPSDH). In this
      method, color interference fringes are captured by a digital camera with a Bayer
      array color filter, and phase shifting is simultaneously performed for all
      wavelengths. Color interference fringes are separated into three monochromatic
      interference fringes using a color-separation method that suppresses the color
      filter crosstalk. The object wave is extracted from each monochromatic
      interference fringe using GPSDH, which prevents problems due to the phase shift
      wavelength dependence. Image reconstruction is performed using a shifted Fresnel
      transform-based method, in which the color reconstructed image is obtained by
      directly superposing the reconstructed images for all wavelengths. We verify the
      proposed method through optical experiments with a two-wavelength digital
      holography system. The results show that the dual-color image can be successfully
      reconstructed without chromatic aberration.

PMID- 29047946
TI  - Experimental study of an optimized PSP-OSTBC scheme with m-PPM in ultraviolet
      scattering channel for optical MIMO system.
AB  - An optimized scheme of pulse symmetrical position-orthogonal space-time block
      codes (PSP-OSTBC) is proposed and applied with m-pulse positions modulation (m
      PPM) without the use of a complex decoding algorithm in an optical multi-input
      multi-output (MIMO) ultraviolet (UV) communication system. The proposed scheme
      breaks through the limitation of the traditional Alamouti code and is suitable
      for high-order m-PPM in a UV scattering channel, verified by both simulation
      experiments and field tests with specific parameters. The performances of 1*1,
      2*1, and 2*2 PSP-OSTBC systems with 4-PPM are compared experimentally as the
      optimal tradeoff between modification and coding in practical application.
      Meanwhile, the feasibility of the proposed scheme for 8-PPM is examined by a
      simulation experiment as well. The results suggest that the proposed scheme makes
      the system insensitive to the influence of path loss with a larger channel
      capacity, and a higher diversity gain and coding gain with a simple decoding
      algorithm will be achieved by employing the orthogonality of m-PPM in an optical
      MIMO-based ultraviolet scattering channel.

PMID- 29047947
TI  - Statistical properties of rectangular cusped random beams propagating in oceanic
      turbulence.
AB  - The analytical formula for the cross-spectral density function of the rectangular
      cusped random beams, also known as fractional multi-Gaussian Schell-model beams,
      propagating in oceanic turbulence, is derived. The statistical properties
      incorporating the spectral density and the spectral degree of coherence of the
      beams on propagation are investigated. It is found that the beams maintain a
      rectangular-shaped cusped profile in weak turbulence just as in free space,
      whereas in strong turbulence or at sufficiently long propagation distances, the
      beams profile would be destroyed little by little, turning out to be Gaussian
      profile eventually. Moreover, the beams with smaller coherence length exhibit a
      more obvious rectangular outline. In addition, the spectral density and the
      spectral degree of coherence are both affected by various turbulence parameters.

PMID- 29047948
TI  - Detection and characterization of chemical aerosol using laser-trapping single
      particle Raman spectroscopy.
AB  - Detection and characterization of the presence of chemical agent aerosols in
      various complex atmospheric environments is an essential defense mission. Raman
      spectroscopy has the ability to identify chemical molecules, but there are
      limited numbers of photons detectable from single airborne aerosol particles as
      they are flowing through a detection system. In this paper, we report on a single
      particle Raman spectrometer system that can measure strong spontaneous,
      stimulated, and resonance Raman spectral peaks from a single laser-trapped
      chemical aerosol particle, such as a droplet of the VX nerve agent chemical
      simulant diethyl phthalate. Using this system, time-resolved Raman spectra and
      elastic scattered intensities were recorded to monitor the chemical properties
      and size variation of the trapped particle. Such a system supplies a new approach
      for the detection and characterization of single airborne chemical aerosol
      particles.

PMID- 29047949
TI  - Temperature sensitivity enhancement of platinum-nanoparticle-coated long period
      fiber gratings fabricated by femtosecond laser.
AB  - The temperature sensing performance of long period fiber gratings (LPFGs) written
      by femtosecond laser pulses coated with platinum nanoparticles (PtNPs) is
      proposed and demonstrated. It is found that the PtNPs increase the wavelength
      sensitivity of the LPFG significantly compared with the bare LPFG. The
      temperature sensitivities of the bare LPFG for three dips, corresponding to 1438,
      1485, and 1585 nm, are 74.04, 77.23, and 86.26  pm/ degrees C, respectively, when
      the temperature changes from 10 degrees C to 500 degrees C, whereas the
      corresponding sensitivities of PtNP coated LPFGs are up to 90.58, 93.51, and
      103.43  pm/ degrees C, respectively. Moreover, the PtNP coated LPFG has shown
      better wavelength repeatability. A small wavelength hysteresis of ~0.5  nm is
      observed when the temperature is less than 300 degrees C.

PMID- 29047950
TI  - Brewster-angle 50%-50% beam splitter for p-polarized infrared light using a high
      index quarter-wave layer deposited on a low-index prism.
AB  - A quarter-wave layer (QWL) of high refractive index, which is deposited on a
      transparent prism of low refractive index, can be designed to split an incident p
      polarized light beam at the Brewster angle (BA) of the air-substrate interface
      into p-polarized reflected and transmitted beams of equal intensity (50% each)
      that travel in orthogonal directions. For reflection of p-polarized light at the
      BA, the supported QWL functions as a free-standing (unsupported) pellicle. An
      exemplary design is presented that uses SixGe1-x QWL deposited on an IRTRAN1
      prism for applications (such as Michelson and Mach-Zehnder interferometry) with a
      variable compositional fraction x in the 2-6 MUm mid-IR spectral range.

PMID- 29047951
TI  - Convex relaxation for illumination control of multi-color multiple-input-multiple
      output visible light communications with linear minimum mean square error
      detection.
AB  - Visible light communications (VLC) using multi-color light-emitting diodes (LEDs)
      can support simultaneous high-speed data rate and high-quality lighting. However,
      since the radiation spectrum of LEDs has a limited width, spectral overlapping
      will result in multi-color cross talk even when optical filters are applied at
      the receivers. Moreover, since LEDs are used for illumination and wireless data
      transmission in the meantime, both lighting quality and communication performance
      must be considered in VLC systems. In this paper, we consider a multiple-input
      multiple-output with low-complexity linear minimum mean square error detection to
      collaboratively manage the cross talk by maximizing the minimum signal-to
      interference-plus-noise ratio (SINR) subject to chromaticity constraint based on
      MacAdam ellipse, luminance constraint, and signal range constraint. A sub-optimal
      convex relaxation is proposed to attack the SINR maximization problem. Extensive
      simulations indicate that the proposed method provides very efficient solutions
      and outperforms the conventional wave-division multiplexing scheme under the
      illumination constraint.

PMID- 29047952
TI  - Depth estimation algorithm for light field data by epipolar image analysis and
      region interpolation.
AB  - In this paper, we propose an optimized algorithm to estimate the depth
      information in the 4D light field data. Our scheme has the advantage of
      conciseness compared to the traditional epipolar-plane image analysis method.
      First, we have analyzed the depth resolution properties of light field data not
      mentioned by the previous researchers. In the depth estimation process, epipolar
      analysis is confined in a small range to reduce the running time, combining with
      a regression test to reduce estimation error. Occlusion condition is especially
      dealt with by recognizing object margin. To test the accuracy of our algorithm,
      we use a benchmark dataset to evaluate the output depth result. We get a
      competitive result in the estimation error evaluation and prevailing runtime
      result compared to that of baseline algorithms. Owing to the high performance,
      this algorithm can be used in real-time depth recognition with the aid of
      parallel computing.

PMID- 29047953
TI  - Optical properties and electronic transitions of zinc oxide, ferric oxide, cerium
      oxide, and samarium oxide in the ultraviolet and extreme ultraviolet.
AB  - Optical properties and electronic transitions of four oxides, namely zinc oxide,
      ferric oxide, cerium oxide, and samarium oxide, are determined in the ultraviolet
      and extreme ultraviolet by reflection electron energy loss spectroscopy using
      primary electron energies in the range 0.3-2.0 keV. This technique allows the
      evaluation of the optical response in these ultraviolet spectral regions of a
      thin layer of material, and the analysis is straightforward. It is performed
      within the dielectric response theory by means of the QUEELS-epsilon(k, omega)
      REELS software developed by Tougaard and Yubero [Surf. Interface Anal.36, 824
      (2004)SIANDQ0142-242110.1002/(ISSN)1096-9918]. The method consists basically in
      the fitting of experimentally determined single-scattering electron energy loss
      cross sections with a parametric energy loss function of the corresponding
      material, to the one calculated within a dielectric response formalism. The
      obtained refractive index and extinction coefficients, as well as the identified
      electronic transitions are compared, when available, with previously published
      results.

PMID- 29047954
TI  - Effects of interface thermal resistance on surface morphology evolution in
      precision glass molding for microlens array.
AB  - To study the effects of the interface thermal resistance on surface morphology
      evolution in precision glass molding (PGM) for microlens array with different
      mold materials, including Tungsten carbide and heat-resistant stainless steel,
      the glass-mold interface thermal resistance is calculated, and heat-transfer
      simulation of PGM based on an interface thermal resistance model at the heating
      stage is conducted correspondingly. The effect of flattening behavior on the
      glass-mold interface is explained. Then, experiments evaluating the relationship
      between heating time and glass surface roughness are carried out, and the glass
      adhesion phenomenon appearing on the heat-resistant stainless steel mold is
      observed and analyzed. Finally, the microlens array is fabricated on the nickel
      phosphorous plating layer on the heat-resistant stainless steel substrate by
      diamond-ball nose-end milling, and experiments of PGM for the microlens array are
      carried out to verify the interface thermal resistance model. The result shows
      that a high-quality surface can be obtained by the combination of a smooth mold
      and rough glass. Compared with the microlens array fabricated with the rough
      glass preform, using the smooth glass preform achieves higher form accuracy
      without defects or blurs.

PMID- 29047955
TI  - Active underwater descattering and image recovery.
AB  - Underwater imaging is a promising but challenging topic due to the scattering
      particles in water, which result in serious light attenuation. Therefore,
      underwater images suffer from low-contrast and low-resolution issues. In this
      study, in order to recover high-quality underwater images, the point spread
      functions (PSFs) are estimated by a slant-edge method. The experiment modulates
      the illumination source to deal with backscattering and the imager to take two
      images in orthogonally polarized states. This imaging method benefits the
      satisfactory edge extraction. The PSF estimation is performed based on the
      extracted slant edge to enable recovery of the image. In addition, the modulation
      transfer function (MTF) is introduced to evaluate the resolution variation with
      the spatial frequencies. It manifests considerable resolution enhancement in the
      recovered images. Moreover, the proposed underwater image recovery method also
      reduces the effect from the scattering as an effective compensation to the
      polarization imaging approach.

PMID- 29047956
TI  - Analysis of a holographic laser adaptive optics system using a deformable mirror.
AB  - We describe a closed-loop holographic laser adaptive optics system (HLAOS) based
      on a holographic wavefront sensor (HWFS) and 21-element continuous-surface
      piezoelectric deformable mirror (DM). The principle behind HWFSs is described,
      and then the response sensitivity and crosstalk effect on the lowest 12 Zernike
      modes of aberration are analyzed. Next, the wavefront-correction capability of
      the 21-element DM is analyzed. The closed-loop correction of the HLAOS to a
      static aberration is then numerically simulated. We report a practical
      implementation of the HLAOS and compare the aberration-compensation effect with a
      traditional adaptive optics system based on a 37-unit Shark-Hartmann sensor. The
      practically relevant parameters are analyzed and the experimental results show
      that an HLAOS using a piezoelectric DM can achieve a correction capability
      comparable to that of a traditional adaptive optics system.

PMID- 29047957
TI  - Diffuse optical localization of blood vessels and 3D printing for guiding oral
      surgery.
AB  - Diffuse optical imaging through centimeters of tissue has emerged as a powerful
      tool in biomedical research. However, applications in the operating theater have
      been limited in part due to data set requirements and computational burden. We
      present an approach that uses a small number of optical source-detector pairs
      that allows for the fast localization of arteries in the roof of the mouth and
      has the potential to reduce complications during oral surgery. The arteries are
      modeled as multiple-point absorbers, allowing localization of their complex
      shapes. The method is demonstrated using a printed tissue-simulating mouth
      phantom. Furthermore, we use the extracted position information to fabricate a
      custom surgical guide using 3D printing that could protect the arteries during
      surgery.

PMID- 29047958
TI  - Improvement in imaging contrast feature of liquid crystal lens with the dopant of
      multi-walled carbon nanotubes.
AB  - An effective method to fabricate a high-contrast imaging liquid crystal (LC) lens
      with a relatively fast response time is proposed. This electrically tunable-focus
      LC lens is doped with multi-walled carbon nanotubes (MWCNTs) and has a high
      resistance layer. A grinding method is utilized to lower agglomeration of doping
      MWCNTs. With respect to the high-resistance layer, it can make maximum use of
      doped nanoparticles to behave with high-quality lens character. The principles of
      improvement in electro-optical properties are discussed. The experimental results
      show that the proposed LC lens is effectively improved. The LC lens has great
      potential in compact imaging systems.

PMID- 29047959
TI  - Far infrared micro-spectroscopy: an innovative method to detect individual metal
      organic framework particles.
AB  - The purpose of this study is to extend the spectral range of a differential
      method of infrared micro-spectroscopy in order to allow the accurate detection of
      nanoparticles of interest for biomedical applications. Among these, metal-organic
      framework (MOF) nanoparticles have attracted increasing interest due to their
      capacity to incorporate high drug payloads, biodegradability, and possibility of
      tailoring their surfaces by grafting specific ligands. However, MOF particle
      detection in biological media without grafting or incorporating fluorescent
      molecules is challenging. We took advantage here of the presence of the specific
      absorption bands of nanoscale MOFs in far infrared in order to individually
      discriminate them. Here we show that single MOF nanoparticles can be imaged with
      a spatial resolution of a few tens of nanometers.

PMID- 29047960
TI  - Noise reduction of air turbulence via thequasi-common-path method.
AB  - In this paper, a quasi-common-path method to improve the stability of laser
      measurement instruments is proposed. The method releases the strictness of the
      common-path structure and enables the compensation of errors caused by air
      turbulence. A wavefront measurement system is set up to simultaneously detect
      both the wavefronts of the quasi-common-path beams, of which the orthogonal
      distance varies from 0 to 4 times the beam diameter. The correlation coefficient
      between two wavefronts remains around 0.9 in turbulence, which verifies the
      feasibility. Based on the method, a three-axis interferometer whose measuring
      optical paths orthogonally split 30 mm is established, and the stability of the
      optical paths is evaluated. The standard deviations of the displacement and the
      displacement difference at the original point are about 0.31 MUm and 0.006 MUm,
      respectively, while these performance properties at 1 m are 1.14 MUm and 0.02
      MUm, respectively. The experimental results show that quasi-common-path beams
      allow for stability improvement, which can also be widely used in the field of
      precision machine manufacturing.

PMID- 29047961
TI  - Localized surface plasmon sensor based on gold island films using a hetero-core
      structured optical fiber.
AB  - This paper reports the effect of applying an Au island film to the hetero-core
      structured optical fiber, which is fabricated by annealing thin Au films with
      thicknesses of 3 and 5 nm and its sensing performance for the refractive index
      changes. We experimentally observe that novel localized surface plasmon resonance
      spectra for 1.333 RIU appear in the visible-to-near-infrared region, depending on
      the shape of Au islands. The absorbance and spectral sensitivity for a given
      refractive index region of the tested solvents were obtained to be 4.81 AU/RIU
      and 517 nm/RIU, respectively, in the range of 1.333-1.384 RIU in the case of 5 nm
      thick Au film annealed at 900 degrees C.

PMID- 29047962
TI  - Influence of dead-time on detection efficiency and range performance of photon
      counting laser radar that uses a Geiger-mode avalanche photodiode.
AB  - Dead-time has a significant influence on the detection efficiency and range
      performance of a photon-counting laser radar system with a Geiger-mode avalanche
      photodiode. In this paper, a rapid universal recursive model of the detection
      probability of discrete time under various dead-times is proposed, which is
      verified with controlled parameters. Our model has the advantage of fast
      computing speed and unifies multi-trigger, single-trigger, and zero-dead-time
      models. The computing speed is 1 to 2 orders of magnitude faster than Gatt's and
      Zhao's models under a short dead-time condition, with relative errors less than
      0.001 and 10-14, respectively. Subsequently, the detection efficiency and range
      bias and precision with various dead-times are theoretically calculated and Monte
      Carlo simulated with different parameters. On the one hand, dead-time shorter
      than the end time of the target achieves better detection efficiency; however,
      this results in worse range performance. On the other hand, dead-time longer than
      the end time of the target maintains the detection efficiency at a low level but
      provides a better range performance. We discover that noise is the key reason for
      the periodic fluctuation of the detection efficiency and range performance versus
      different dead-times and the local optimum values of fluctuations occur when the
      dead-time is a few nanoseconds shorter or longer than 1, 1/2, 1/3, or even 1/4 of
      the end time of the target; further, this phenomenon becomes more evident when
      noise increases. Moreover, weaker noise level is crucial to the detection
      efficiency, and narrow pulse width and nearer target position in the range gate
      are important factors to improve precision.

PMID- 29047963
TI  - Reduction of chromatic dispersion using multiple carrier frequency patterns in
      SLM-based microscopy.
AB  - Typically, spatial light modulator (SLM)-based microscopy is implemented using a
      carrier frequency in order to avoid disturbances due to the non-ideal modulation
      behavior of most SLMs. However, in combination with polychromatic light, this
      leads to strong chromatic aberrations due to the dispersion at the grating formed
      by the carrier frequency. In this contribution, we introduce a method based on
      the evaluation of multiple images obtained with different carrier frequency
      orientations. This way, chromatic aberrations and the limitation concerning the
      object field can be strongly reduced.

PMID- 29047964
TI  - Laboratory demonstration of a cryogenic deformable mirror for wavefront
      correction of space-borne infrared telescopes.
AB  - This paper demonstrates a cryogenic deformable mirror (DM) with 1020 actuators
      based on micro-electrical mechanical systems (MEMS) technology. Cryogenic space
      borne infrared telescopes can experience a wavefront error due to a figure error
      of their mirror surface, which makes the imaging performance worse. For on-orbit
      wavefront correction as one solution, we developed a MEMS-processed electro
      static DM with a special surrounding structure for use under the cryogenic
      temperature. We conducted a laboratory demonstration of its operation in three
      cooling cycles between 5 K and 295 K. Using a laser interferometer, we detected
      the deformation corresponding to the applied voltages under the cryogenic
      temperature for the first time. The relationship between voltages and
      displacements was qualitatively expressed by the quadratic function, which is
      assumed based on the principle of electro-static DMs. We also found that it had a
      high operating repeatability of a few nm root-mean-square and no significant
      hysteresis. Using the measured values of repeatability, we simulated the
      improvement of the point spread function (PSF) by wavefront correction with our
      DM. These results show that our developed DM is effective in improving imaging
      performance and PSF contrast of space-borne infrared telescopes.

PMID- 29047965
TI  - Velocity measurement based on multiple self-mixing interference.
AB  - This study proposes a novel algorithm based on the multiple self-mixing
      interference (MSMI) theory to measure the velocity of a remote target without
      contact. The principle of MSMI is presented and the corresponding formulas for
      velocity measurement are derived. Fast Fourier transform is applied to detect
      signal frequency and calculate velocity values. A low-cost, compact, and easy-to
      operate experimental setup is also constructed. Experiments are conducted to
      validate the correctness of our algorithm. This algorithm can improve resolution
      more easily than conventional self-mixing interference methods.

PMID- 29047966
TI  - Laser confocal cylindrical radius measurement method and its system.
AB  - This paper proposes a laser confocal cylindrical radius of the curvature
      measurement (CCRM) method. The CCRM method precisely identifies the positions of
      the vertex and curvature center of the test cylindrical surface by using the
      property so that the maximum point of the laser confocal axial intensity curve
      precisely corresponds to the focus of the laser confocal measurement system, and
      the accurate distance of these two positions is obtained by the distance
      measuring instrument, thus achieving the precise measurement of the cylindrical
      radius. The quadratic fitting method is used to further improve the measurement
      accuracy. Compared with existing measurement methods, the CCRM method has high
      measurement precision, simple structure, and strong environmental interference
      capability, and it is more suitable for engineering applications. Based on the
      CCRM, the CCRM system is established, and theoretical analysis and preliminary
      experiments indicate that the relative uncertainty of cylindrical radius
      measurement is better than 0.045%. Therefore, the CCRM provides an effective
      approach for the high-precision measurement of cylindrical radius.

PMID- 29047967
TI  - Fast and accurate phase-unwrapping algorithm based on the transport of intensity
      equation.
AB  - The phase information of a complex field is routinely obtained using coherent
      measurement techniques as, e.g., interferometry or holography. The obtained
      measurement result is subject to a 2pi ambiguity and is often referred to as
      wrapped phase. Phase-unwrapping algorithms (PUAs) are commonly employed to remove
      this ambiguity and, hence, obtain the absolute phase. However, implementing PUAs
      can be computationally intensive, and the accuracy of those algorithms may be
      low. Recently, the transport of intensity equation (TIE) has been proposed as a
      simple and practical alternative for obtaining the absolute phase map.
      Nevertheless, an efficient implementation of this technique has not yet been
      made. In this work, we propose an accurate solution for the TIE-based PUA that
      does not require the use of wave-propagation techniques, as previously reported
      TIE-based approaches. The proposed method calculates directly the axial
      derivative of the intensity from the wrapped phase when considering the correct
      propagation method. This is done in order to bypass the time-consuming wave
      propagation techniques employed in similar methods. The analytical evaluation of
      this parameter allows obtaining an accurate solution when unwrapping the phase
      map with low computational effort. This work further introduces the use of the
      iterative TIE-PUA that, in a few steps, improves significantly the accuracy of
      the final absolute phase map, even in the presence of noise or aliasing of the
      wrapped data. The high accuracy and utility of the developed TIE-PUA technique is
      proven by both numerical simulations and experiments for various objects.

PMID- 29047968
TI  - Line-scanning laser scattering system for fast defect inspection of a large
      aperture surface.
AB  - Inspection of defects with micrometer level on large aperture surfaces with
      hundreds of millimeters is one of the challenges in surface quality evaluation.
      Various microscopic imaging methods have been applied to inspecting the surface
      defects, while they are time-consuming for the small field of view and the sub
      aperture stitching. To tackle this problem, a high-speed line scanning system
      based on the dark-field laser scattering method is proposed. The laser beam is
      scanned by the rotating polygon mirror to a laser line for high throughput and
      then the telecentric F-theta lens converges each incoming laser beam to a focused
      spot that creates a high intensity to enhance the signal-to-noise ratio. The
      scattered light from surface defect is collected by the designed integrating
      sphere for low background noise and the scattering signal is detected for each
      focused spot at a proper acquisition rate by a photomultiplier (PMT) detector
      with extremely short response time. In the meanwhile, the tested surface is
      moving perpendicular to the laser line to realize high-speed large area
      inspection. The defect inspection system is confirmed experimentally with laser
      line length of 60 mm, minimum detectable size less than 0.5 MUm, and figure of
      merit of 9.6  cm2 s-1 MUm-1. The work put forward an effective method for
      automatic discovery of surface defects such as scratches, digs, and contaminants
      on large aperture surfaces.

PMID- 29047969
TI  - Ion-exchanged binary phase plates for mode multiplexing in graded-index optical
      fibers.
AB  - Few-mode graded-index optical fibers are being increasingly relevant in spatial
      division multiplexing. Likewise, multi-region binary phase plates are fundamental
      elements for some mode multiplexing schemes in such optical fibers. In this work,
      we propose a coupling configuration for mode multiplexing based on collimating
      focusing graded-index lenses together with binary phase plates, and calculate, in
      a fully analytical and quasi-analytical way, the theoretical conversion
      efficiencies and crosstalks between the fields generated by such plates and the
      Laguerre-Gaussian modes. These modes describe, directly or by a linear
      combination of them, the first optical modes of many graded-index optical fibers.
      The results obtained provide both the illumination conditions of the plates and
      their optical characteristics. The fabrication of the plates is made by using ion
      exchange technology and their optical characterization by beam profilometry. The
      experimental conversion efficiencies are in agreement with the theoretical
      results.

PMID- 29047970
TI  - Demonstration of 3D computed tomography of chemiluminescence with a restricted
      field of view.
AB  - Three-dimensional imaging techniques have experienced a surge in research
      interest during the past few years due to advancements in both hardware, i.e.,
      the sensor arrays and data acquisition systems, and new imaging concepts, such as
      light field imaging and compressed sensing. Computed tomography of
      chemiluminescence (CTC) is an intriguing technique for combustion diagnostics due
      to its ease of implementation, as no excitation source is required in
      measurements. It has been applied extensively for the retrieval of intermediate
      species such as CH*/OH*, from which the flame topology can be obtained. However,
      all previous demonstrations or applications were performed under the assumption
      that a complete field of view is available for all projections. However, this
      prerequisite cannot be guaranteed for some practical scenarios, such as engine
      measurements, in which optical access is extremely limited and a portion of the
      field of view is unavoidably blocked, especially when a considerable number of
      projections are required. This work aims to develop an improved CTC modality that
      can handle projections with a restricted field of view, and to suggest the best
      strategy for tomographic reconstruction under such experimental conditions.
      Although this technique is discussed under the context of combustion diagnostics,
      it can also be useful and adapted for other tomographic areas, such as biomedical
      imaging.

PMID- 29047971
TI  - Decomposition and correction overlapping peaks of LIBS using an error
      compensation method combined with curve fitting.
AB  - The laser induced breakdown spectroscopy (LIBS) technique is an effective method
      to detect material composition by obtaining the plasma emission spectrum. The
      overlapping peaks in the spectrum are a fundamental problem in the qualitative
      and quantitative analysis of LIBS. Based on a curve fitting method, this paper
      studies an error compensation method to achieve the decomposition and correction
      of overlapping peaks. The vital step is that the fitting residual is fed back to
      the overlapping peaks and performs multiple curve fitting processes to obtain a
      lower residual result. For the quantitative experiments of Cu, the Cu-Fe
      overlapping peaks in the range of 321-327 nm obtained from the LIBS spectrum of
      five different concentrations of CuSO4.5H2O solution were decomposed and
      corrected using curve fitting and error compensation methods. Compared with the
      curve fitting method, the error compensation reduced the fitting residual about
      18.12-32.64% and improved the correlation about 0.86-1.82%. Then, the calibration
      curve between the intensity and concentration of the Cu was established. It can
      be seen that the error compensation method exhibits a higher linear correlation
      between the intensity and concentration of Cu, which can be applied to the
      decomposition and correction of overlapping peaks in the LIBS spectrum.

PMID- 29047972
TI  - Design, fabrication, and demonstration of a dielectric vortex waveguide in the
      sub-terahertz region.
AB  - A sub-terahertz vortex dielectric waveguide was designed and fabricated in the
      cyclic olefin copolymer (TOPAS) compound. The annular index profile was
      engineered using a holey cladding to support operation from approximately 200-300
      GHz. The vortex waveguide was tested at 280 GHz using an OAM-endowed Laguerre
      Gaussian mode generated by a stepped spiral phase plate.

PMID- 29047973
TI  - Figuring process of potassium dihydrogen phosphate crystal using ion beam
      figuring technology.
AB  - Currently, ion beam figuring (IBF) technology has presented many excellent
      performances in figuring potassium dihydrogen phosphate (KDP) crystals, such as
      it is a noncontact figuring process and it does not require polishing fluid. So,
      it is a very clean figuring process and does not introduce any impurities.
      However, the ion beam energy deposited on KDP crystal will heat the KDP crystal
      and may generate cracks on it. So, it is difficult directly using IBF technology
      to figure KDP crystal, as oblique incident IBF (OI-IBF) has lower heat
      deposition, higher removal rate, and smoother surface roughness compared to
      normal incident IBF. This paper studied the process of using OI-IBF to figure KDP
      crystal. Removal rates and removal functions at different incident angles were
      first investigated. Then heat depositions on a test work piece were obtained
      through experiments. To validate the figuring process, a KDP crystal with a size
      of 200  mm*200  mm*12  mm was figured by OI-IBF. After three iterations using the
      OI-IBF process, the surface error decreases from the initial values with PV
      1.986lambda RMS 0.438lambda to PV 0.215lambda RMS 0.035lambda. Experimental
      results indicate that OI-IBF is feasible and effective to figure KDP crystals.

PMID- 29047974
TI  - Mean estimation empirical mode decomposition method for terahertz time-domain
      spectroscopy de-noising.
AB  - The wavelet-domain de-noising technique has many applications in terahertz time
      domain spectroscopy (THz-TDS). However, it requires a complex procedure for the
      selection of the optimal wavelet basis and threshold, which varies for different
      materials. Inappropriate selections can lead to de-noising failure. Here, we
      propose the Mean Estimation Empirical Mode Decomposition (ME-EMD) de-noising
      method for THz-TDS. First, the THz-TDS signal and the collected reference noise
      are decomposed into the intrinsic mode functions (IMFs); second, the maximum and
      mean absolute values of the noise IMF amplitudes are calculated and defined as
      the adaptive threshold and adaptive estimated noise value, respectively; finally,
      these thresholds and estimated noise values are utilized to filter the noise from
      the signal IMFs and reconstruct the THz-TDS signal. We also calculate the signal
      to-noise ratio (SNR) and mean square error (MSE) for the ME-EMD method, the "db7"
      wavelet basis, and the "sym8" wavelet basis after de-noising in both the
      simulation and the real sample experiments. Both theoretical analysis and
      experimental results demonstrated that the new ME-EMD method is a simple,
      effective, and high-stability de-noising tool for THz-TDS pulses. The measured
      refractive index curves are compared before and after de-noising and demonstrated
      that the de-noising process is necessary and useful for measuring the optical
      constants of a sample.

PMID- 29047976
TI  - Reflectivity and transmissivity of a surface covered by a disordered monolayer of
      large and tenuous particles: theory versus experiment.
AB  - The main objective of this paper is to endorse a recently derived theoretical
      model for the coherent reflectance and transmittance from a surface supporting a
      disordered monolayer of large and tenuous particles by comparison with
      experimental measurements. The model is based on the so-called anomalous
      diffraction approximation and is assumed to be valid for small and moderate
      angles of incidence. We prepared disordered monolayers of spherical polystyrene
      particles of 1.8 MUm diameter and of human red blood cells on glass microscope
      slides. In both cases, particles were immersed in a liquid of refractive index
      close to that of the particle. We measured the relative reflectivity and
      transmissivity of the samples versus the wavelength of light at normal incidence
      and the reflectivity and transmissivity versus the angle of incidence at a fixed
      wavelength, and compared with predictions of the anomalous-diffraction
      approximation model. For the polystyrene particle samples, we also compare the
      results with another available theoretical model developed some years ago to deal
      with disordered monolayers of highly scattering particles. In the case of red
      blood cell monolayers, we also present measurements with a hemolyzed sample and a
      disordered multilayer film for comparison. We find that the anomalous diffraction
      model can be fitted very well to the experimental curves, in some cases, even for
      high angles of incidence.

PMID- 29047975
TI  - Breast density quantification using structured-light-based diffuse optical
      tomography simulations.
AB  - We present the feasibility of structured-light-based diffuse optical tomography
      (DOT) to quantify the breast density with an extensive simulation study. This
      study is performed on multiple numerical breast phantoms built from magnetic
      resonance imaging (MRI) images. These phantoms represent realistic tissue
      morphologies and are given typical breast optical properties. First, synthetic
      data are simulated at five wavelengths using our structured-light-based DOT
      forward problem. Afterwards, the inverse problem is solved to obtain the
      absorption images and subsequently the chromophore concentration maps.
      Parameters, such as segmented volumes and mean concentrations, are extracted from
      these maps and used in a regression model to estimate the percent breast
      densities. These estimations are correlated with the true values from MRI,
      r=0.97, showing that our new technique is promising in measuring breast density.

PMID- 29047977
TI  - Controllable direction of liquid jets generated by thermocavitation within a
      droplet.
AB  - A high-velocity fluid stream ejected from an orifice or nozzle is a common
      mechanism to produce liquid jets in inkjet printers or to produce sprays among
      other applications. In the present research, we show the generation of liquid
      jets of controllable direction produced within a sessile water droplet by
      thermocavitation. The jets are driven by an acoustic shock wave emitted by the
      collapse of a hemispherical vapor bubble at the liquid-solid/substrate interface.
      The generated shock wave is reflected at the liquid-air interface due to acoustic
      impedance mismatch generating multiple reflections inside the droplet. During
      each reflection, a force is exerted on the interface driving the jets. Depending
      on the position of the generation of the bubble within the droplet, the
      mechanical energy of the shock wave is focused on different regions at the liquid
      air interface, ejecting cylindrical liquid jets at different angles. The ejected
      jet angle dependence is explained by a simple ray tracing model of the
      propagation of the acoustic shock wave inside the droplet.

PMID- 29047978
TI  - Determination of point of incidence for the case of reflection or refraction at
      spherical surface knowing two points lying on the ray.
AB  - The paper is focused on the problem of determination of the point of incidence of
      a light ray for the case of reflection or refraction at the spherical optical
      surface, assuming that two fixed points in space that the sought light ray should
      go through are given. The requirement is that one of these points lies on the
      incident ray and the other point on the reflected/refracted ray. Although at
      first glance it seems to be a simple problem, it will be shown that it has no
      simple analytical solution. The basic idea of the solution is given, and it is
      shown that the problem leads to a nonlinear equation in one variable. The roots
      of the resulting nonlinear equation can be found by numerical methods of
      mathematical optimization. The proposed methods were implemented in MATLAB, and
      the proper function of these algorithms was verified on several examples.

PMID- 29047979
TI  - Theoretical imaging study of early caries by a laser induced Rayleigh wave.
AB  - Vivo human teeth are scanned by computed tomography through three-dimensional
      (3D) reconstruction technology. Geometric models of teeth are built. Based on
      that, a physical model of the laser induced acoustic waves propagating in teeth
      is established, and the finite element method is used to solve this physical
      model. As the velocity of the Rayleigh wave is sensitive to the elastic modulus
      of the teeth, the parameters, such as the position, demineralization degree,
      depth, and morphology of the caries, can be evaluated by the velocity field of
      the Rayleigh wave, which propagate in teeth. Furthermore, by the frequency domain
      characters of surface acoustic waves, the depth of the caries region can be
      evaluated. Therefore, the 3D evaluation method is established to develop the
      nondestructive and quantitative detection of the early stages of caries.

PMID- 29047980
TI  - Signal-to-noise ratio enhancement of a Hadamard transform spectrometer using a
      two-dimensional slit-array.
AB  - The encoding and decoding principle of the Hadamard transform spectrometer with a
      2D slit-array mask is described in this paper. Based on the Hadamard transform
      theory, the signal-to-noise ratio (SNR) enhancement of a 2D slit-array Hadamard
      transform spectrometer is deduced and verified experimentally. Affected by the
      optical system of the spectrometer, there are differences between the
      experimental results and theoretical calculations. At the end of this paper, we
      discuss the influence of the spectrometer's optical system on the SNR enhancement
      based on the spatial frequency analysis.

PMID- 29047981
TI  - Validation of a gonio-hyperspectral imaging system based on light-emitting diodes
      for the spectral and colorimetric analysis of automotive coatings.
AB  - In this study, a novel gonio-hyperspectral imaging system based on light-emitting
      diodes for the analysis of automotive coatings was validated colorimetrically and
      spectrally from 368 to 1309 nm. A total of 30 pearlescent, 30 metallic, and 30
      solid real automotive coatings were evaluated with this system, the BYK-mac and X
      Rite MA98 gonio-spectrophotometers, and also with the SPECTRO 320 spectrometer
      for further comparison. The results showed very precise correlations, especially
      in the visible range. In conclusion, this new system provides a deeper assessment
      of goniochromatic pigments than current approaches due to the expansion of the
      spectral range to the infrared.

PMID- 29047982
TI  - Self-correction of projector nonlinearity in phase-shifting fringe projection
      profilometry.
AB  - In phase-shifting fringe projection profilometry, the luminance nonlinearity of
      the used projector has been recognized as one of the most crucial factors
      decreasing the measurement accuracy. To solve this problem, this paper presents a
      self-correcting technique that allows us to suppress the effect of the projector
      nonlinearity in the absence of any calibration data regarding the projector
      intensities or regarding the phase errors. In its first step, the standard phase
      shifting algorithm is used to recover the phases, as well as the background
      intensities and the modulations. Using these results enables normalizing the
      fringe patterns, for ridding them of the effects of the background and
      modulations. Second, we smooth the calculated phase map by use of a low-pass
      filter in order to remove the ripple-like phase errors induced by the projector
      nonlinearity. Third, we determine a polynomial representing the projector
      nonlinearity by fitting the curve of the normalized fringe intensities against
      the cosine values of the smoothed phases. Finally, we correct the phase errors
      using the curve just obtained. Doing these steps in an iterative way eventually
      results in a phase map and, further, a 3D shape with their artifacts induced by
      the projector nonlinearity suppressed significantly. Experimental results
      demonstrate that this technique offers some advantages over others. It does not
      require a prior calibration of the projector, thus being suitable for dealing
      with a time-variant nonlinearity; its pointwise operation protects the edges and
      details of the measurement results from being blurred; and it works well with
      very few fringe patterns and is efficient in image capturing.

PMID- 29047983
TI  - Simplified paraboloid phase model-based phase tracker for demodulation of a
      single complex fringe.
AB  - A regularized phase tracker (RPT) is an effective method for demodulation of
      single closed-fringe patterns. However, lengthy calculation time, specially
      designed scanning strategy, and sign-ambiguity problems caused by noise and
      saddle points reduce its effectiveness, especially for demodulating large and
      complex fringe patterns. In this paper, a simplified paraboloid phase model-based
      regularized phase tracker (SPRPT) is proposed. In SPRPT, first and second phase
      derivatives are pre-determined by the density-direction-combined method and
      discrete higher-order demodulation algorithm, respectively. Hence, cost function
      is effectively simplified to reduce the computation time significantly. Moreover,
      pre-determined phase derivatives improve the robustness of the demodulation of
      closed, complex fringe patterns. Thus, no specifically designed scanning strategy
      is needed; nevertheless, it is robust against the sign-ambiguity problem. The
      paraboloid phase model also assures better accuracy and robustness against noise.
      Both the simulated and experimental fringe patterns (obtained using electronic
      speckle pattern interferometry) are used to validate the proposed method, and a
      comparison of the proposed method with existing RPT methods is carried out. The
      simulation results show that the proposed method has achieved the highest
      accuracy with less computational time. The experimental result proves the
      robustness and the accuracy of the proposed method for demodulation of noisy
      fringe patterns and its feasibility for static and dynamic applications.

PMID- 29047984
TI  - 1018  nm Yb-doped high-power fiber laser pumped by broadband pump sources around
      915  nm with output power above 100  W.
AB  - We demonstrate a 1018 nm ytterbium-doped all-fiber laser pumped by tunable pump
      sources operating in the broad absorption spectrum around 915 nm. In the
      experiment, two different pump diodes were tested to pump over a wide spectrum
      ranging from 904 to 924 nm by altering the cooling temperature of the pump
      diodes. Across this so-called pump wavelength regime having a 20 nm wavelength
      span, the amplified stimulated emission (ASE) suppression of the resulting laser
      was generally around 35 dB, showing good suppression ratio. Comparisons to the
      conventional 976 nm-pumped 1018 nm ytterbium-doped fiber laser were also
      addressed in this study. Finally, we have tested this system for high power
      experimentation and obtained 67% maximum optical-to-optical efficiency at an
      approximately 110 W output power level. To the best of our knowledge, this is the
      first 1018 nm ytterbium-doped all-fiber laser pumped by tunable pump sources
      around 915 nm reported in detail.

PMID- 29047985
TI  - Quantitative phase imaging by optimized asymmetric illumination.
AB  - We have presented a simple approach for quantitative phase imaging by optimizing
      asymmetric illumination of a conventional microscope. With this illumination, the
      light intensity modulation accompanying refraction at the surface profile of
      phase objects occurs, and "phase-gradient information" can be derived by
      detecting it. Two images with phase-gradient information on different axes are
      converted into the two-dimensional phase distribution of the specimen by
      introducing the phase-gradient transfer function, which is the intensity change
      due to refraction by the phase-gradient of a specimen. We experimentally confirm
      accurate and repeatable performance of our method and demonstrate phase imaging
      of live cells.

PMID- 29047986
TI  - Temperature-tunable one-dimensional plasmonic photonic crystals based on a single
      graphene layer and a semiconductor constituent.
AB  - We first investigate a graphene based 1D plasmonic photonic crystal (PPC)
      composed of a graphene sheet deposited on an SiO2 grating whose grooves are
      filled with air by using finite-element method (FEM) software (COMSOL
      Multiphysics). The dispersion effect of SiO2 is considered in the simulation, and
      we show that this effect significantly affects the transmission spectrum of the
      proposed PPC. The transmission spectrum shows a stop band in the mid-infrared
      region, which is blueshifted by increasing the Fermi energy level of the graphene
      sheet. However, the transmission spectrum is not affected by variation of the
      ambient temperature. To achieve a temperature-tunable 1D graphene-based PPC, we
      propose that the graphene sheet be placed on a grating composed of InAs
      semiconductor material. Our results confirm that the stop band in the proposed
      structure can be easily tuned with temperature and moves to higher frequencies by
      increasing the ambient temperature. Moreover, we introduce a defect into the
      temperature-tunable PPC to obtain a temperature-tunable Fabry-Perot microcavity.
      It is demonstrated that the resonance defect mode is easily controllable by
      changing the temperature and the Fermi energy level.

PMID- 29047987
TI  - Microsphere-assisted phase-shifting profilometry.
AB  - In the present work, we have investigated the combination of a superresolution
      microsphere-assisted 2D imaging technique with low-coherence phase-shifting
      interference microscopy. The imaging performance of this technique is studied by
      numerical simulation in terms of the magnification and the lateral resolution as
      a function of the geometrical and optical parameters. The results of simulations
      are compared with the experimental measurements of reference gratings using a
      Linnik interference configuration. Additional measurements are also shown on
      nanostructures. An improvement by a factor of 4.7 in the lateral resolution is
      demonstrated in air, thus giving a more isotropic nanometric resolution for full
      field surface profilometry in the far field.

PMID- 29047988
TI  - Highly birefringent, highly negative dispersion compensating photonic crystal
      fiber.
AB  - A triangular lattice dispersion compensating photonic crystal fiber is presented
      in this paper. The fiber produces high birefringence and operates at fundamental
      mode only. The full vector finite element method with a perfectly matched
      absorbing layer boundary condition is applied to investigate the guiding
      properties of the proposed fiber. The designed fiber demonstrates that it is
      possible to obtain a very large negative dispersion of -9486.1  ps/(nm.km) at
      1550 nm wavelength with a negative dispersion more than -7000  ps/(nm.km) over
      the entire C-band (1530-1565 nm), which is suitable for broadband dispersion
      compensation. The birefringence is about 4.13*10-2 at 1550 nm wavelength, which
      is also very high. All these properties make this fiber very suitable in the area
      of broadband dispersion compensation and polarization-maintaining applications.

PMID- 29047989
TI  - Bi-directional ultrasonic wave coupling to FBGs in continuously bonded optical
      fiber sensing.
AB  - Fiber Bragg grating (FBG) sensors are typically spot-bonded onto the surface of a
      structure to detect ultrasonic waves in laboratory demonstrations. However, to
      protect the rest of the optical fiber from any environmental damage during real
      applications, bonding the entire length of fiber, called continuous bonding, is
      commonly done. In this paper, we investigate the impact of continuously bonding
      FBGs on the measured Lamb wave signal. In theory, the ultrasonic wave signal can
      bi-directionally transfer between the optical fiber and the plate at any adhered
      location, which could potentially produce output signal distortion for the
      continuous bonding case. Therefore, an experiment is performed to investigate the
      plate-to-fiber and fiber-to-plate signal transfer, from which the signal coupling
      coefficient of each case is theoretically estimated based on the experimental
      data. We demonstrate that the two coupling coefficients are comparable, with the
      plate-to-fiber case approximately 19% larger than the fiber-to-plate case.
      Finally, the signal waveform and arrival time of the output FBG responses are
      compared between the continuous and spot bonding cases. The results indicate that
      the resulting Lamb wave signal output is only that directly detected at the FBG
      location; however, a slight difference in signal waveform is observed between the
      two bonding configurations. This paper demonstrates the practicality of using
      continuously bonded FBGs for ultrasonic wave detection in structural health
      monitoring (SHM) applications.

PMID- 29047990
TI  - Integrated optical readout using a hybrid plasmonic directional coupler in water.
AB  - The integrated polymer optical readout has been recognized as a promising route
      to obtain miniaturized cantilever-based sensor works on static mode for various
      liquid-state chemical and biological measurements in portable lab-on-chip
      systems. For conventional optical readouts based on end-fire coupling mechanisms,
      the most sensitive region was limited to a cantilever deflection of several
      micrometers due to the Gaussian profile of the mode in polymer waveguides. We
      proposed an integrated optical readout based on a hybrid plasmon directional
      coupler aiming at improving the sensitivity at the sub-micrometer deflection
      region (<1  MUm). The coupler consists of a short-range surface plasmon waveguide
      and a polymer waveguide. We show that the coupling length and the propagation
      loss of the coupler are ultra-sensitive to the deflection, which leads to
      improved sensitivity of the readout. In addition, the dynamic range can be
      extended by integrating an array of hybrid plasmon directional couplers onto a
      single microcantilever. The proposed optical readout is beneficial to high
      sensitivity cantilever-based sensors for lab-on-chip applications and enables the
      design of more compact optical waveguide-based sensors in water.

PMID- 29047991
TI  - MWIR thermal imaging spectrometer based on the acousto-optic tunable filter.
AB  - Mid-wavelength IR (MWIR) thermal imaging spectrometers are widely used in remote
      sensing, industrial detection, and military applications. The acousto-optic
      tunable filter (AOTF)-based spectrometer has the advantages of fast tuning, light
      weight, and no moving parts, which make it ideally suited for MWIR applications.
      However, when designing an AOTF imaging spectrometer, the traditional method uses
      a refractive grating or parallel glass model in optical design software to
      simulate the AOTF, lowering the imaging performance of the optical system. In
      this paper, an accurate simulating model for an actual MWIR AOTF using the user
      defined surface function in ZEMAX is presented, and an AOTF-based MWIR thermal
      imaging spectrometer is designed and tested successfully. It is based on a MWIR
      tellurium dioxide (TeO2) AOTF with an operational spectral range from 3.0 to 5.0
      MUm and a spectral resolution of 30.8 nm at 3.392 MUm. The optical system employs
      a three-mirror off-axis afocal telescope with a 2.4 degrees *2.0 degrees  field
      of view. The operation of the MWIR thermal imaging spectrometer and its image
      acquisition are computer controlled. Furthermore, the imaging spectrometer is
      tested in the laboratory, and several experiments are also presented. The
      experimental results indicate that the proposed AOTF model is efficient, and also
      show that the imaging spectrometer has the ability to distinguish the real hot
      target from the interfering target effectively.

PMID- 29047992
TI  - Analyses of optical rays in KTN optical beam deflectors for device design.
AB  - The potassium tantalate niobate (KTN) optical beam deflector is an electro-optic
      deflector without any moving parts that works at frequencies higher than 200 kHz.
      In this paper, we discuss the performance parameters of this deflector. Optical
      beams are bent by the spatial distribution of the refractive index in the KTN
      crystal block used in this deflector. In addition to the deflection function, the
      index distribution operates as a cylindrical convex lens. Therefore, the
      deflector is often used with glass cylindrical lenses to cancel out the lens
      function. We analyzed optical rays curving in the block based on the graded index
      lens theory. We describe the way in which performance parameters, such as the
      deflection angle, change, depending on both the choice of the compensating lenses
      and the parameters of the KTN block, namely its size and charge density. We
      concentrate especially on methods designed to improve the resolvable spot number,
      which is the most important figure of merit for optical deflectors. One way to
      achieve improvement is to input a collimated beam or a slightly converging beam
      into the KTN block.

PMID- 29047993
TI  - Sub-millimeter depth-resolved digital holography.
AB  - We present sub-millimeter full-field depth from focus digital holography of
      surface topography of rough objects. For each pixel, the depth of the object is
      calculated from the variance of the intensity image over a set of reconstruction
      distances. First, we theoretically describe the axial resolution of this method
      and show that sub-millimeter resolution is feasible. Second, using a digital
      holography setup without magnifying optics or lateral scanning we experimentally
      demonstrate 100 MUm axial resolution depth ranging and surface topography
      imaging. This is significantly better than what has previously been reported
      using digital holography and could make this technique useful for rapid large
      area characterization of surface topography of objects.

PMID- 29047995
TI  - Using refraction in thick glass plates for optical path length modulation in low
      coherence interferometry.
AB  - In Michelson interferometer setups the standard way to generate different optical
      path lengths between a measurement arm and a reference arm relies on expensive
      high precision linear stages such as piezo actuators. We present an alternative
      approach based on the refraction of light at optical interfaces using a cheap
      stepper motor with high gearing ratio to control the rotation of a glass plate.
      The beam path is examined and a relation between angle of rotation and change in
      optical path length is devised. As verification, an experimental setup is
      presented, and reconstruction results from a measurement standard are shown. The
      reconstructed step height from this setup lies within 1.25% of the expected
      value.

PMID- 29047994
TI  - Ultrashort polarization rotator based on spiral photonic crystal fiber aided by
      liquid crystal.
AB  - A novel polarization rotator (PR) is proposed based on a spiral photonic crystal
      fiber aided by liquid crystal. The proposed PR has an ultrashort length of only
      ~4.17  MUm and a low cross talk of ~-20.93  dB, and the proposed PR offers a
      nearly 100% polarization conversion efficiency for the whole C-band. In addition,
      a large temperature tolerance of ~+/-5 degrees C and a large rotation angle
      tolerance of ~+/-4 degrees  can be accepted based on the full-vector finite
      element method simulation. The proposed PR is a potentially effective
      polarization conversion device for applications in modern communication systems.

PMID- 29047996
TI  - Vector mode conversion based on an asymmetric fiber Bragg grating in few-mode
      fibers.
AB  - We propose a vector mode conversion approach based on asymmetric fiber Bragg
      gratings (AFBGs) written in step-index fiber and vortex fiber, respectively. The
      mode coupling properties of AFBGs are numerically investigated. Compared to step
      index fiber, the large mode separation in the vortex fiber is beneficial to
      extracting the desired vector mode at specific wavelengths. In addition, the
      polarization of incident light and the attenuation coefficient of index change
      distribution of the AFBG play critical roles in the mode coupling process. The
      proposed AFBG provides an efficient method to realize high-order vector mode
      conversion, and it shows great potential for orbital angular momentum
      multiplexing and fiber lasers with vortex beam output.

PMID- 29047997
TI  - Aerosol optical properties and direct radiative forcing at Taihu.
AB  - Ground-based characteristics (optical, type, size, and radiative properties) of
      aerosols measured between 2005 and 2012 were investigated over the Taihu rim
      region, which encompasses the cities of Shanghai, Suzhou, Wuxi, and Changzhou.
      The aerosol optical depth (AOD) showed a distinct seasonal variation with the
      highest value in summer and the lowest AOD in winter. There was broadest
      frequency distribution with a multimodal structure in summer. The Angstrom
      exponent (AE) showed high values during spring; the relative frequency of AE in
      the range of 0-0.8 was 5-10 times greater than that of other seasons. The samples
      with high AOD440 and low AE440-870 were mainly observed in spring, which is
      attributed to the relative abundance of coarse particles. The monthly aerosol
      volume size distributions presented a bimodal structure (fine and coarse modes).
      The coarse mode was dominant during spring, while the fine mode was predominant
      in other seasons. The main aerosol type over Taihu during all the seasons was the
      mixed small-particle category, followed by the urban/industrial category. The
      minimum single scattering albedo (SSA) occurred in winter, suggesting that
      atmosphere aerosol had a higher absorption. All monthly averaged asymmetry
      factors (ASY) had positive values and no distinct seasonal variation. Both high
      real (Re) and imaginary (Im) parts of the refractive index occurred in winter.
      The atmospheric warming effect of aerosol was more significant in winter compared
      with other seasons, with the averaged atmosphere aerosol radiative forcing (ARF)
      and the corresponding atmospheric heating rate up to +69.46  W.m-2 and 1.95 
      K.day-1, respectively. There existed a significant positive correlation between
      AOD and ARF (absolute value), and the correlation coefficients (r) exceeded 0.86
      in each season with maximum r in summer. Along with the increasing of the SSA,
      the aerosol radiative forcing efficiency (absolute value) showed a decreasing
      trend at the bottom of the atmosphere and an increasing trend at the top of the
      atmosphere.

PMID- 29047998
TI  - Fundamental uncertainty limit for speckle displacement measurements.
AB  - The basic metrological task in speckle photography is to quantify displacements
      of speckle patterns, allowing for instance the investigation of the mechanical
      load and modification of objects with rough surfaces. However, the fundamental
      limit of the measurement uncertainty due to photon shot noise is unknown. For
      this reason, the Cramer-Rao bound (CRB) is derived for speckle displacement
      measurements, representing the squared minimal achievable measurement
      uncertainty. As result, the CRB for speckle patterns is only two times the CRB
      for an ideal point light source. Hence, speckle photography is an optimal
      measurement approach for contactless displacement measurements on rough surfaces.
      In agreement with a derivation from Heisenberg's uncertainty principle, the CRB
      depends on the number of detected photons and the diffraction limit of the
      imaging system described by the speckle size. The theoretical results are
      verified and validated, demonstrating the capability for displacement
      measurements with nanometer resolution.

PMID- 29047999
TI  - Double-sided telecentric zoom lens consisting of four tunable lenses with fixed
      distance between object and image plane.
AB  - This work performs a paraxial analysis of the double-sided telecentric zoom lens
      consisting of four tunable lenses with fixed distance between the object and
      image plane. Equations enabling calculation of paraxial parameters of such
      optical systems are derived and the calculation is presented on examples. To our
      knowledge the presented analysis is novel and such optical systems have not been
      investigated yet.

PMID- 29048000
TI  - Beam diameter thresholds as applying light depolarization for effective submicron
      and micron root mean square roughness evaluation.
AB  - To further study the microscopic mechanism and beam diameter effect during light
      depolarization (LDP), we developed a compact laser instrument (lambda=632.8  nm)
      with an adjustable beam diameter of >=18  MUm (approximately 28lambda). Six
      nickel plate samples with rms roughness, Rq, of 42 nm to 2.3 MUm (i.e., 0.067
      3.7lambda) fabricated by the fine-honing method are examined. To analyze the beam
      diameter effect as applying LDP for submicron and micron Rq evaluation, the cross
      sectional beam-spot size (BSS) is adjusted from 20 MUm to 650 MUm during off
      specular inspections. The results of BSS <=40  MUm (i.e., 60lambda) have a 10-nm
      level Rq sensitivity, while those of BSS >=140  MUm (220lambda) have about a 100
      times weaker sensitivity. It means that BSS of 60lambda and 220lambda should have
      instructional significance as applying LDP for precision levels of 10 nm and 1
      MUm surface roughness analyses, respectively. In addition, since the instrument
      is simple, portable, stable, and low-cost, it has great potential for both LDP
      analyses and practical online roughness testing.

PMID- 29048001
TI  - Self-shading associated with a skylight-blocked approach system for the
      measurement of water-leaving radiance and its correction.
AB  - Self-shading associated with a skylight-blocked approach (SBA) system for the
      measurement of water-leaving radiance (Lw) and its correction [Appl. Opt.52, 1693
      (2013)APOPAI0003-693510.1364/AO.52.001693] is characterized by Monte Carlo
      simulations, and it is found that this error is in a range of ~1%-20% under most
      water properties and solar positions. A model for estimating this shading error
      is further developed, and eventually a scheme to correct this error based on the
      shaded measurements is proposed and evaluated. It is found that the shade
      corrected value in the visible domain is within 3% of the true value, which thus
      indicates that we can obtain not only high precision but also high accuracy Lw in
      the field with the SBA scheme.

PMID- 29048002
TI  - Investigation for connecting waveguide in off-planar integrated circuits.
AB  - The transmission properties of a vertical waveguide connected by different
      devices in off-planar integrated circuits are designed, investigated, and
      analyzed in detail by the finite-difference time-domain method. The results show
      that both guide bandwidth and transmission efficiency can be adjusted effectively
      by shifting the vertical waveguide continuously. Surprisingly, the wide guide
      band (0.385[c/a]~0.407[c/a]) and well transmission (-6  dB) are observed
      simultaneously in several directions when the vertical waveguide is located at a
      specific location. The results are very important for all-optical integrated
      circuits, especially in compact integration.

PMID- 29048003
TI  - Wander of the short-term spreading filter for partially coherent Gaussian beams
      through the anisotropic turbulent ocean.
AB  - The models of the short-term spreading and wander of the short-term spreading
      filter for partially coherent Gaussian beams propagating in an anisotropic
      oceanic turbulence are established by considering the effect of irradiance
      fluctuations on beam wander. The results of beam wander based on our model are
      larger than Andrews and Phillips's model, which considers the effect of the beam
      wander twice and weakens the effect of irradiance fluctuations on the beam
      wander. The results of our model show that the short-term spreading and wander of
      beams increase as the rate of dissipation of kinetic energy per unit mass of
      fluid and the emitting beam radius decrease, but they increase as the dissipation
      rate of temperature variance increases. As the temperature fluctuation of the
      oceanic turbulence gets stronger, the beam wander rises first and then turns into
      the wander saturation. The larger inner scale of turbulence and larger spatial
      coherent radius will decrease the short-term spreading of the beam and increase
      the beam wander. It also indicates that the anisotropy can restrain the impact of
      the turbulence to some extent in the oceanic channel. The salinity fluctuation
      has a greater impact on both short-term spreading and wander of the beam than
      temperature fluctuation does in oceanic turbulence.

PMID- 29048004
TI  - Double-pulse 1.57  MUm integrated path differential absorption lidar ground
      validation for atmospheric carbon dioxide measurement.
AB  - A ground-based double-pulse integrated path differential absorption (IPDA)
      instrument for carbon dioxide (CO2) concentration measurements at 1572 nm has
      been developed. A ground experiment was implemented under different conditions
      with a known wall located about 1.17 km away acting as the scattering hard
      target. Off-/offline testing of a laser transmitter was conducted to estimate the
      instrument systematic and random errors. Results showed a differential absorption
      optical depth (DAOD) offset of 0.0046 existing in the instrument. On-/offline
      testing was done to achieve the actual DAOD resulting from the CO2 absorption.
      With 18 s pulses average, it demonstrated that a CO2 concentration measurement of
      432.71+/-2.42  ppm with 0.56% uncertainty was achieved. The IPDA ranging led to a
      measurement uncertainty of 1.5 m.

PMID- 29048005
TI  - Improved generation method utilizing a modified Fourier spectrum for Airy beams
      with the phase-only filter technique.
AB  - We present an improved method to generate Airy beams utilizing a liquid crystal
      on silicon (LCoS) device. In this method, the phase and amplitude information of
      a modified Fourier spectrum of an Airy beam together with a Fresnel holographic
      lens is encoded onto the LCoS using the phase-only filter technique; thus, a
      desired Airy beam is formed in the focal plane of the Fresnel holographic lens.
      In this paper, the principle of the proposed method is described in detail, and
      both the excellent numerical simulations and experimental results for verifying
      this method are demonstrated. It is shown that the new generation method is
      accurate and simple; in particular, the setup is more compact compared to the
      conventional Fourier transform method, which comprises only the input polarized
      laser and a LCoS device. This effective method will further promote
      investigations into the properties and applications of Airy beams.

PMID- 29048006
TI  - Error analysis of the calibration of a dual-rotating-retarder Mueller matrix
      polarimeter.
AB  - We previously developed a Mueller matrix microscope by combining a dual-rotating
      retarder device with a commercial microscope, which holds promise for pathologic
      diagnosis applications. In practical applications, the signals to be measured are
      sensitive to systematic errors, and the measurement accuracy and the instrument
      calibration affect the capacity to characterize the data. In conventional
      calibration, the initial positions of the rotating devices are constrained,
      causing calibration instability. To improve the calibration, we examine the
      mathematical model of the calibration process using previous studies, and derive
      a calibration algorithm with reduced error magnification. Our experimental
      results show the proposed algorithm improves calibration accuracy, and provides
      more robust results.

PMID- 29048007
TI  - 1  kHz single-frequency 2.09  MUm Ho:YAG ring laser.
AB  - In this paper, we report the experimental realization of a high-repetition-rate
      single-frequency Ho-doped yttrium aluminum garnet (Ho:YAG) ring laser at 2.09
      MUm. Single-frequency operation of the ring laser is achieved by injection
      seeding with a continuous wave (CW) Ho:YAG non-planar ring oscillator (NPRO)
      laser. The output energy of the ring laser is 6.24 mJ with a pulse width of 172
      ns and a repetition rate of 1 kHz. The beam quality M2-factor is measured to be
      ~1.3 at the maximum output energy. The half-width of the pulse spectrum is
      measured to be 2.61 MHz by a heterodyne technique.

PMID- 29048008
TI  - Design of an all-optical fractional-order differentiator with terahertz bandwidth
      based on a fiber Bragg grating in transmission.
AB  - All-optical fractional-order temporal differentiators with bandwidths reaching
      terahertz (THz) values are demonstrated with transmissive fiber Bragg gratings.
      Since the designed fractional-order differentiator is a minimum phase function,
      the reflective phase of the designed function can be chosen arbitrarily. As
      examples, we first design several 0.5th-order differentiators with bandwidths
      reaching the THz range for comparison. The reflective phases of the 0.5th-order
      differentiators are chosen to be linear phase, quadratic phase, cubic phase, and
      biquadratic phase, respectively. We find that both the maximum coupling
      coefficient and the spatial resolution of the designed grating increase when the
      reflective phase varies from quadratic function to cubic function to biquadratic
      function. Furthermore, when the reflective phase is chosen to be a quadratic
      function, the obtained grating coupling coefficient and period are more likely to
      be achieved in practice. Then we design fractional-order differentiators with
      different orders when the reflective phase is chosen to be a quadratic function.
      We see that when the designed order of the differentiator increases, the obtained
      maximum coupling coefficient also increases while the oscillation of the coupling
      coefficient decreases. Finally, we give the numerical performance of the designed
      0.5th-order differentiator by showing its temporal response and calculating its
      cross-correlation coefficient.

PMID- 29048009
TI  - MEMS tracking mirror system for a bidirectional free-space optical link.
AB  - We report on a bidirectional free-space optical system that is capable of
      automatic connection and tracking of an optical link between two nodes. A
      piezoelectric micro-electro-mechanical systems (MEMS) optical scanner is used to
      steer a laser beam of two wavelengths superposed to visually present a
      communication zone, to search for the position of the remote node by means of the
      retro-reflector optics, and to transmit the data between the nodes. A feedback
      system is developed to control the MEMS scanner to dynamically establish the
      optical link within a 10-ms transition time and to keep track of the moving node.

PMID- 29048010
TI  - Complexity-enhanced polarization-resolved chaos in a ring network of mutually
      coupled vertical-cavity surface-emitting lasers with multiple delays.
AB  - The complexity properties of polarization-resolved chaotic signals generated in a
      ring network of vertical-cavity surface-emitting lasers (VCSELs) mutually coupled
      with multiple delays are investigated quantitatively by using the proposed mean
      permutation entropy (MPE). For direct comparison, the complexity of polarization
      resolved chaos in a ring network of VCSELs coupled with single delay is also
      considered. The effects of injection current, coupling strength, and frequency
      detuning on the chaotic complexity for both a single-delay ring network (SDRN)
      and a multiple-delay ring network (MDRN) are evaluated quantitatively and
      compared by the MPE. The effects of internal parameters of VCSELs on the
      complexity are also discussed, and the correlation properties between different
      polarization-resolved modes are also analyzed. It is shown that the complexity of
      chaos in two polarization-resolved modes of VCSELs in MDRN is much higher than
      those in SDRN in a much wider parameter region. Besides, wider range of injection
      current, coupling strength, and frequency detuning can be tuned to achieve the
      enhancement of chaotic complexity in MDRN. These results provide an effective
      quantifier, the proposed MPE, to evaluate quantitatively the complexity of chaos
      generated in systems with multiple delays, and the multichannel complexity
      enhanced polarization-resolved chaos generated in MDRN of mutually coupled VCSELs
      is extremely meaningful for the chaos-based random number generators.

PMID- 29048011
TI  - Directional backlighting system using a light guide with paired microstructures.
AB  - In a conventional edge-lit backlighting system, a light guide with diffusing
      dots, prism films and diffusers are used to produce desired light distribution.
      In such a system, the use of prism films helps to collimate the light, but it
      also increases the cost and reduces the overall optical efficiency. This paper
      proposes a novel light guide with paired microstructures to produce highly
      collimated light distribution without using prism films. Each paired
      microstructure is composed of two different micro-geometries that are placed next
      to each other. By optimizing the surface angles of a paired microstructure in the
      light guide, a highly collimated light distribution can be generated without
      using prism films.

PMID- 29048012
TI  - Generation of a square pulse with ultra-wide tuning range in a passively mode
      locked Yb-doped fiber laser.
AB  - We have experimentally demonstrated a square pulse in a passively mode-locked Yb
      doped fiber ring laser operating in the dissipative soliton resonance (DSR)
      region based on the nonlinear polarization rotation technique. In our experiment,
      a 1.5-km long single-mode fiber (SMF) is inserted into the cavity to increase the
      cavity length. The total cavity is 1501.8 m. With increasing pump power, the
      pulse duration can be tuned from 209.8 ns to 812.4 ns without wave-breaking, and
      the maximum output single pulse energy is 42.34 nJ. To the best of our knowledge,
      this is the widest pulse in any Yb-doped mode-locked fiber laser. Moreover, the
      relationship between pulse width and cavity length is investigated. When the
      total cavity length is decreased to 1001.8 m and 501.8 m, the tuning range of
      square pulse is 372.4 ns (from 58.6 ns to 431 ns) and 138 ns (from 26 ns to 164
      ns), respectively, and the maximum output single pulse energy is 13.85 nJ and
      8.75 nJ, respectively.

PMID- 29048013
TI  - Adaptive optics retinal imaging with automatic detection of the pupil and its
      boundary in real time using Shack-Hartmann images.
AB  - Retinal imaging with an adaptive optics (AO) system usually requires that the eye
      be centered and stable relative to the exit pupil of the system. Aberrations are
      then typically corrected inside a fixed circular pupil. This approach can be
      restrictive when imaging some subjects, since the pupil may not be round and
      maintaining a stable head position can be difficult. In this paper, we present an
      automatic algorithm that relaxes these constraints. An image quality metric is
      computed for each spot of the Shack-Hartmann image to detect the pupil and its
      boundary, and the control algorithm is applied only to regions within the
      subject's pupil. Images on a model eye as well as for five subjects were obtained
      to show that a system exit pupil larger than the subject's eye pupil could be
      used for AO retinal imaging without a reduction in image quality. This algorithm
      automates the task of selecting pupil size. It also may relax constraints on
      centering the subject's pupil and on the shape of the pupil.

PMID- 29048014
TI  - Weighted reconstruction of three-dimensional refractive index in interferometric
      tomography.
AB  - Interferometric tomography can reconstruct 3D refractive-index distributions
      through phase-shift measurements for different beam angles. To reconstruct a
      complex refractive-index distribution, many projections along different
      directions are required. For the purpose of increasing the number of the
      projections, we earlier proposed a beam-angle-controllable interferometer with
      mechanical stages; however, the quality of reconstructed distribution by
      conventional algorithms was poor because the background fringes cannot be
      precisely controlled. To improve the quality, we propose a weighted
      reconstruction algorithm that can consider projection errors. We demonstrate the
      validity of the weighted reconstruction through simulations and a reconstruction
      from experimental data for three candle flames.

PMID- 29048015
TI  - Computer-aided-design-model-assisted absolute three-dimensional shape
      measurement.
AB  - Conventional three-dimensional (3D) shape measurement methods are typically
      generic to all types of objects. Yet, for many measurement conditions, such a
      level of generality is inessential when having the preknowledge of the object
      geometry. This paper introduces a novel adaptive algorithm for absolute 3D shape
      measurement with the assistance of the object computer-aided-design (CAD) model.
      The proposed algorithm includes the following major steps: (1) export the 3D
      point cloud data from the CAD model; (2) transform the CAD model into the camera
      perspective; (3) obtain a wrapped phase map from three phase-shifted fringe
      images; and (4) retrieve absolute phase and 3D geometry assisted by the CAD
      model. We demonstrate that if object CAD models are available, such an algorithm
      is efficient in recovering absolute 3D geometries of both simple and complex
      objects with only three phase-shifted fringe images.

PMID- 29048016
TI  - Affordable dispersion mitigation method for the next generation RF-over-fiber
      optical channels.
AB  - Next-generation analog radio frequency over fiber (RFoF) links will require
      dispersion compensation. Most dispersion compensation methods are based on
      additional optical elements. Therefore, these solutions may be inadequate for low
      cost channels. In this work, we suggest a novel low-cost dispersion compensation
      solution for RFoF links. The method is based on two properties, which are common
      in these links: the modulation depth in analog RFoF links is lower than in
      digital links (and to avoid nonlinearities, it may be deliberately set to a small
      value), and the data are carried by a high-frequency carrier. It is shown that
      with these properties, the optical channel behaves approximately as a linear
      system. The distortion occurs in the linear domain and in the third-harmonic
      regime. Since the third-harmonic distortions are usually smaller than the back-to
      back distortions, they are linear in the power domain. We therefore suggest using
      a simple low-cost electronic filter to compensate the dispersion distortions. The
      performance of this technique is presented both analytically and with a numerical
      simulation. These preliminary results are very encouraging and point to an
      inexpensive solution for next-generation RFoF links to the home.

PMID- 29048017
TI  - Joint sparse and low rank recovery algorithm for compressive hyperspectral
      imaging.
AB  - Compressive spectral imaging techniques encode and disperse a hyperspectral image
      (HSI) to sense its spatial and spectral information with few bidimensional (2D)
      multiplexed projections. Recovering the original HSI from the 2D projections is
      carried by traditional compressive sensing-based techniques that exploit the
      sparsity property of natural HSI as they are represented in a proper orthonormal
      basis. Nevertheless, HSIs also exhibit a low rank property inasmuch only a few
      numbers of spectral signatures are present in the images. Specifically, when an
      HSI is rearranged as a matrix whose columns represent vectorized 2D spatial
      images in a different wavelength, this matrix is said to be low rank. Therefore,
      this paper proposes an HSI recovering algorithm from compressed measurements
      involving a joint sparse and low rank optimization problem, which seeks to
      jointly minimize the l2-, l1-, and l*-norm, leading the solution to fit the given
      projections, and be simultaneously sparse and low rank. Several simulations,
      along different data sets and optical sensing architectures, show that when the
      low rank property is included in the inverse problem formulation, the
      reconstruction quality increases up to four (dB) in terms of peak signal to noise
      ratio.

PMID- 29048018
TI  - Point target detection based on multiscale morphological filtering and an energy
      concentration criterion.
AB  - The research on optical imaging characteristics of infrared dim point targets in
      the presence of nonstationary cloud clutter and random noise is necessary for
      target detection. We analyze the energy concentration of point targets that are
      less than 3*3 pixels in size and deduce a simulation model of the point target
      imaging process. Then we adopt omnidirectional multiscale structural elements to
      detect all the possible targets distributing in every direction. The adaptive
      threshold and the energy concentration criterion are employed to eliminate false
      alarms. Finally, the trajectory of point targets is obtained after the low-order
      recursive correlation. The results show that the detection probability of the
      proposed method reaches 99.8% with 0.2% false alarm probability. It demonstrates
      that the proposed method has a good performance to suppress complex background
      and random noise. Also, it has the advantage of low complexity and easy
      implementation in a real-time system.

PMID- 29048019
TI  - Sampling moire technique for determination of optical transfer function of
      digital imaging systems.
AB  - In this paper, the optical transfer function (OTF) of a digital imaging system is
      determined by different frequencies' sinusoidal gratings in two stages of before
      and after the Nyquist frequency. Before the Nyquist frequency, modulation
      transfer function (MTF) and visibility are equivalent, and the phase transfer
      function (PTF) does not change with phase variation of the initial object
      gratings. Sampling of the grating with frequency above the Nyquist frequency
      gives rise to sampling moire fringes. In this situation, the MTF is unusually
      bigger than 1 and is not equivalent to the visibility of the sampling moire, but
      the PTF shows two different behaviors before and after the Nyquist frequency.
      Before the Nyquist frequency, the PTF does not depend on the initial phase
      variation of the grating, but after the Nyquist frequency, the PTF depends on the
      initial phase variation. Therefore, the PTF of the sampling moire is proposed for
      phase variation detection.

PMID- 29048020
TI  - Non-perturbing voltage measurement in a coaxial cable with slab-coupled optical
      sensors.
AB  - Voltage in a coaxial cable is measured by an electric-field optical fiber sensor
      exploiting the proportionality of voltage and electric field in a fixed
      structure. The sensor is inserted in a hole drilled through the dielectric of the
      RG-218 coaxial cable and sealed with epoxy to displace all air and prevent the
      adverse effects of charge buildup during high-voltage measurements. It is shown
      that the presence of the sensor in the coaxial cable does not significantly
      increase electrical reflections in the cable. A slab-coupled optical fiber sensor
      (SCOS) is used for its compact size and dielectric make. The dynamic range of 50
      dB is shown experimentally with detection of signals as low as 1 V and up to 157
      kV. A low corner of 0.3 Hz is demonstrated and the SCOS is shown to be able to
      measure 90 ns rise time.

PMID- 29048021
TI  - 3D pose estimation of large and complicated workpieces based on binocular stereo
      vision.
AB  - A binocular stereo vision method is proposed for automatically locating the
      position and posture of workpieces, which is especially important when processing
      large, complicated structures, for example, the laser hardening and laser
      cladding of automotive die. First, a binocular stereo vision positioning system
      was designed and modeled, from which a method of background subtraction was
      proposed to extract the edge line of the foreground area. Furthermore, the
      intersection point of the workpiece contour line was taken as the characteristic
      point of the workpiece, and an algorithm that combines epipolar constraint with
      gray value similarity was proposed to quickly and accurately realize the feature
      points matching. Finally, experiments show that the workpiece can be positioned
      accurately, and that the precision of position recognition could be controlled
      within +/-0.5  mm when the camera was 1 m away from the workpiece, meeting the
      requirement of robot processing.

PMID- 29048022
TI  - Polarization properties of receiving telescopes in atmospheric remote sensing
      polarization lidars.
AB  - A receiving telescope is an indispensable component in an atmospheric remote
      sensing polarization lidar. In order to achieve accurate atmospheric
      depolarization measurements, it is necessary to study the polarization properties
      of receiving telescopes, which are embodied by their Mueller matrices. In this
      paper, the Mueller matrices of receiving telescopes are obtained by ray tracing
      with space vectors. The relationship between the measurement errors of the
      atmospheric depolarization parameter and the elements of the Mueller matrix of
      receiving telescopes is derived. The polarization properties of receiving
      telescopes in terms of orientation, field of view, and F number are analyzed,
      respectively. By comparing two common receiving telescopes in linear and circular
      polarization lidars, it is found that the measurement errors caused by the Newton
      telescopes in circular polarization lidars are significantly greater than those
      in linear polarization lidars, while the performances of the Cassegrain
      telescopes in the two lidars are almost identical. What is more, the measurement
      errors caused by the Cassegrain telescopes are much less than the counterparts
      caused by the Newton telescopes. According to the comparison results, the optimal
      telescopes are respectively presented for polarization lidars working in
      different polarization states and laser wavelengths.

PMID- 29048023
TI  - Generalized sequential four-step phase-shifting color digital holography.
AB  - A generalized sequential four-step phase-shifting color digital holography is
      proposed. As an arbitrary phase-shift quantity is independent from wavelengths,
      it can be used for four-step phase-shifting color digital holography.
      Furthermore, no constraint on the phase-shifting quantities or statistical
      property on the hologram is required in the proposed method. Experimental results
      using a reflective object are shown to confirm the proposed phase-shifting
      digital holography.

PMID- 29048024
TI  - Random bit generation using coherent state and threshold detectors at 1550
      nanometers.
AB  - We theoretically propose and experimentally validate a practical random bit
      generation method based on the detections of a coherent state in the few-photon
      regime by a gated single-photon threshold detector, operating at the telecom
      wavelength of 1550 nanometers. By fine tuning the mean number of photons per
      pulse of a laser beam directed to the single-photon detector, a 50-50 chance of
      detection or no-detection is reached; under this condition, detections inside the
      gate window are treated as "1"s, while "0"s are associated with the absence of
      detections. The same method could also be applied in a free-running single-photon
      detector for increased throughput by chopping the light signal instead of gating
      the detector. Both hardware implementations yielded bit strings, which were
      evaluated by a standard randomness test suite with good confidence. Despite the
      yet low rates achieved by the proposed method, its hardware compatibility with
      quantum key distribution setups makes it an interesting candidate for random
      number generation within the context of practical quantum communications.

PMID- 29048025
TI  - One-step real-virtual combined reflection hologram: a 4f relay approach.
AB  - The production of conventional optical reflection holograms can be classified
      into the one-step method or the two-step method. In the one-step method, only the
      diverging light of an object can be recorded, and the reconstructed scene is a
      virtual one behind the recording medium. In the two-step method, the diverging
      light or the converging light can be recorded alternatively. However, the process
      is complicated considering double exposures. The object is first imaged by a 4f
      system, and then the interference patterns are recorded by single exposure. The
      reconstructed image can be either a virtual image behind the recording medium or
      a real image in front of the recording medium. The ideal imaging property of a 4f
      system has been demonstrated theoretically, and the proposed method has been
      verified experimentally.

PMID- 29048026
TI  - Bounds of parameter estimation for interference signals.
AB  - Parameter estimation, especially frequency estimation, from noisy observations of
      interference is essential in optical interferometric sensing and metrology. The
      Cramer-Rao bound (CRB) of such estimation determines measurement sensitivity
      limit. Unlike the well-studied complex sinusoids in communication theory, an
      optical interference signal is distinctly different in its model parameters and
      noise statistics. The connection between these parameters and their estimation
      bounds has not been well understood. Here we propose a complete, realistic
      multiparameter interference model corrupted by a combination of shot noise, dark
      noise, and readout noise. We derive the Fisher information matrix and the CRBs
      for all model parameters, including intensity, visibility, optical path length
      (frequency), and initial phase. We show that the CRBs of frequency and phase are
      coupled but not affected by the knowledge of intensity and visibility. Knowing
      the initial phase offers significant sensitivity advantage, which is verified by
      both theoretical derivations and numerical simulations. In addition to the
      complete model, a shot noise-limited case is studied, permitting the calculation
      of the CRBs directly from measured data.

PMID- 29048027
TI  - Measurement error analysis for polarization extinction ratio of multifunctional
      integrated optic chips.
AB  - Measurement error for the polarization extinction ratio (PER) of a
      multifunctional integrated optic chip (MFIOC) utilizing white light
      interferometry was analyzed. Three influence factors derived from the all-fiber
      device (or optical circuit) under test were demonstrated to be the main error
      sources, including: 1) the axis-alignment angle (AA) of the connection point
      between the extended polarization-maintaining fiber (PMF) and the chip PMF
      pigtail; 2) the oriented angle (OA) of the linear polarizer; and 3) the
      birefringence dispersion of PMF and the MFIOC chip. Theoretical calculations and
      experimental results indicated that by controlling the AA range within 0 degrees
      +/-5 degrees , the OA range within 45 degrees +/-2 degrees  and combining with
      dispersion compensation process, the maximal PER measurement error can be limited
      to under 1.4 dB, with the 3sigma uncertainty of 0.3 dB. The variations of
      birefringence dispersion effect versus PMF length were also discussed to further
      confirm the validity of dispersion compensation. A MFIOC with the PER of ~50  dB
      was experimentally tested, and the total measurement error was calculated to be
      ~0.7  dB, which proved the effectiveness of the proposed error reduction methods.
      We believe that these methods are able to facilitate high-accuracy PER
      measurement.

PMID- 29048028
TI  - Re-examining the effect of particle phase functions on the remote-sensing
      reflectance.
AB  - Even though it is well known that both the magnitude and detailed angular shape
      of scattering (phase function, PF), particularly in the backward angles, affect
      the color of the ocean, the current remote-sensing reflectance (Rrs) models
      typically account for the effect of its magnitude only through the backscattering
      coefficient (bb). Using 116 volume scattering function (VSF) measurements
      previously collected in three coastal waters around the U.S. and in the water of
      the North Atlantic Ocean, we re-examined the effect of particle PF on Rrs in four
      scenarios. In each scenario, the magnitude of particle backscattering (i.e., bbp)
      is known, but the knowledge on the angular shape of particle backscattering is
      assumed to increase from knowing nothing about the shape of particle PFs to
      partially knowing the particle backscattering ratio (Bp), the exact
      backscattering shape as defined by beta~p(gamma>=90 degrees ) (particle VSF
      normalized by the particle total scattering coefficient), and the exact
      backscattering shape as defined by the chip factor (particle VSF normalized by
      the particle backscattering coefficient). At sun zenith angle=30 degrees , the
      nadir-viewed Rrs would vary up to 65%, 35%, 20%, and 10%, respectively, as the
      constraints on the shape of particle backscattering become increasingly stringent
      from scenarios 1 to 4. In all four scenarios, the Rrs variations increase with
      both viewing and sun angles and are most prominent in the direction opposite the
      sun. Our results show a greater impact of the measured particle PFs on Rrs than
      previously found, mainly because our VSF data show a much greater variability in
      Bp, beta~p(gamma>=90 degrees ), and chip than previously known. Among the
      uncertainties in Rrs due to the particle PFs, about 97% can be explained by chip,
      90% by beta~p(gamma>=90 degrees ), and 27% by Bp. The results indicate that the
      uncertainty in ocean color remote sensing can be significantly constrained by
      accounting for chip of the VSFs.

PMID- 29048029
TI  - Superconductor based ternary periodic multilayered structure as a single and
      multichanneled filter in the terahertz region.
AB  - A single as well as a multichanneled filter in the terahertz region has been
      proposed by designing a one-dimensional photonic crystal (PhC) structure using a
      high-temperature superconductor air-dielectric ternary periodic structure. The
      filter is designed without incorporating any defect, which has rarely been
      proposed in a ternary PhC structure. The theoretical study of transmittance was
      performed by applying the transfer matrix method. The transition from single
      channel to desired multichannel is achieved by adjusting the number of periods.
      Furthermore, the impact of the thicknesses and dielectric constants of the
      constituting layers was investigated. In addition to this, the tunability is
      achieved by the influence of temperature-dependent dielectric constant of the
      superconductor.

PMID- 29048030
TI  - Continuously tunable mode-spacing of a dual-mode external cavity InAs/InP quantum
      dot laser.
AB  - A tunable double-mode external cavity InAs/InP quantum dot laser based on a dual
      Littrow configuration is demonstrated. A 115 nm single-mode tuning spectrum with
      obviously varied mode intensity has been obtained. A modified tuning method has
      been adopted to realize continuously tunable mode-spacing between two modes. It
      is found that single and double modes coexist in the tuning spectrum when one
      grating angle is fixed while the other grating is rotated; the biggest mode
      spacing between double modes is about 75 nm. A continuously tunable range of mode
      spacing between double wavelengths has reached up to 80 nm by inserting an
      attenuation slice in the external optical feedback paths to balance the intensity
      of the double modes; the separation of double modes is about 50 nm at best. The
      average output power of the double-mode laser is about a few milliwatts.

PMID- 29048031
TI  - Ultrasound-to-plastic optical fiber coupling as an acoustic source probe.
AB  - An integrated ultrasonic detection system that consists of emission and detection
      has been proposed and demonstrated experimentally. The proposed emission source
      is based on plastic optical fiber (POF). In order to promote the coupling of
      ultrasound-to-POF, and the end of the POF is heated to form a circular pedestal.
      A homemade fiber Fabry-Perot interferometer is employed to evaluate the coupling
      efficiency of ultrasound-to-POF. The sensing head is spliced with a short section
      of hollow-core fiber and single-mode fiber, resulting in an air microbubble
      formation by discharging. The experimental results show that ultrasound can be
      transmitted effectively in a narrow space using the coupling method, and the
      compact sensor also presents a considered sensitivity for ultrasonic detection.
      This all-fiber ultrasonic interrogation can be integrated as a system for the
      application in the bioimaging field, especially the organism body.

PMID- 29048032
TI  - Comparison of hyperspectral imaging spectrometer designs and the improvement of
      system performance with freeform surfaces.
AB  - Hyperspectral-grating-based imaging spectrometer systems with F/3 and covering
      the visual-near-infrared (420-1000 nm) spectral range are investigated for
      monitoring Earth's environmental changes. The systems have an entrance slit of 24
      MUm and a 6.5 nm spectral resolution. Both smile and keystone distortions are
      smaller than 20% of the pixel pitch. We benefit from the development in freeform
      technology and design 15 different systems with the help of off-axis aspheric and
      freeform surfaces. The potential of each system is explored with the help of
      nonspherical surfaces. Cross comparisons between different system types are
      summarized to give their advantages and disadvantages. In the end, detailed
      tolerancing of one selected system is presented to show the feasibility for
      fabrication.

PMID- 29048033
TI  - Effect of laser intensity on temporal and spectral features of laser generated
      acoustic shock waves: ns versus ps laser pulses.
AB  - Evolution of acoustic shock wave (ASW) properties generated during nanosecond
      (ns) and picosecond (ps) laser-induced breakdown (LIB) of atmospheric air at
      different input intensities is presented. The intensity is varied by changing the
      focal geometry of ns and ps pulses. The ASW pressures are observed to follow the
      dynamic interplay between the plasma density and recombination of plasma species.
      The conversion of laser energy to acoustic energy has increased from loose to
      tight focusing conditions. The central frequencies have moved toward the lower
      side with increasing laser intensities for both ns-LIB (76-48 kHz) and ps-LIB
      (111.2-92.1 kHz). The angular distribution of acoustic emissions was observed to
      follow the laser-induced plasma spark in both ns- and ps-LIB.

PMID- 29048034
TI  - Confocal laser displacement sensor using a micro-machined varifocal mirror.
AB  - A confocal laser displacement sensor using a micro-machined varifocal mirror is
      reported. The focal length modulation is a key function of the confocal sensor.
      The mechanism of the focal length modulation determines the measurement speed and
      range. Here, we propose application of the micro-machined varifocal mirror for
      the modulation. The varifocal mirror can realize faster modulation, small size,
      and low energy consumption for the confocal displacement sensor. The
      electrostatically actuated varifocal mirror made by single crystalline silicon is
      used. The working distance of the sensor is designed to be 31 mm. The actuating
      range at 7 kHz is 310 MUm. The linearity error in the actuating range is from 
      1.1% to 1.2%.

PMID- 29048035
TI  - Effect of self-absorption correction on surface hardness estimation of Fe-Cr-Ni
      alloys via LIBS.
AB  - The effect of self-absorption was investigated on the estimation of surface
      hardness of Fe-Cr-Ni metallic alloys by the laser-induced breakdown spectroscopy
      (LIBS) technique. For this purpose, the linear relationship between the ratio of
      chromium ionic to atomic line intensities (CrII/CrI) and surface hardness was
      studied, both before and after correcting the self-absorption effect. The
      correlation coefficient significantly increased from 47% to 90% after self
      absorption correction. The results showed the measurements of surface hardness
      using LIBS can be more accurate and valid by correcting the self-absorption
      effect.

PMID- 29048036
TI  - Thermal effects in an ultrafast BiB3O6 optical parametric oscillator at high
      average powers.
AB  - An ultrafast, high-average-power, extended-cavity, femtosecond BiB3O6 optical
      parametric oscillator was constructed as a test bed for investigating the
      scalability of infrared parametric devices. Despite the high pulse energies
      achieved by this system, the reduction in slope efficiency near the maximum
      available pump power prompted the investigation of thermal effects in the crystal
      during operation. The local heating effects in the crystal were used to determine
      the impact on both phase matching and thermal lensing to understand limitations
      that must be overcome to achieve microjoule-level pulse energies at high
      repetition rates.

PMID- 29048037
TI  - Pattern-illuminated Fourier ptychography microscopy with a pattern-estimation
      algorithm.
AB  - In this paper we proposed a new method that combines random pattern illumination,
      the pattern-estimation algorithm, and the Fourier ptychography (FP) algorithm to
      recover a super-resolution image. We shifted one multispot pattern to different
      positions to capture images, and estimated these illumination patterns using a
      gradient descent algorithm that shares the same root with blind structured
      illumination microscopy (SIM). Based on the captured images and estimated
      patterns, the FP algorithm is then applied to recover a super-resolution image.
      Our method, termed as pattern-estimated Fourier ptychography (PEFP) microscopy,
      does not need the prior information about the scanning position, and is thus
      insensitive to rotational errors and shift errors. The performance of PEFP has
      been demonstrated both in simulations and experiments, and PEFP achieves better
      resolution than the pattern-illuminated FP method when shift errors appear in our
      simulations. Moreover, PEFP shows strong resistance towards aberrations and works
      fine when there is noise in the captured image. Compared with a newly proposed
      blind-SIM method, PEFP also shows better resolution enhancement both in our
      simulations and experiments. Our method also provides the possibility to extend
      the application of pattern-illuminated FP to any illumination pattern because we
      estimated every illumination pattern separately, as blind-SIM does.

PMID- 29048038
TI  - Fluorescence lifetime evaluation of whole soils from the Amazon rainforest.
AB  - Time-resolved fluorescence spectroscopy (TRFS) is a new tool that can be used to
      investigate processes of interaction between metal ions and organic matter (OM)
      in soils, providing a specific analysis of the structure and dynamics of
      macromolecules. To the best of our knowledge, there are no studies in the
      literature reporting the use of this technique applied to whole/non-fractionated
      soil samples, making it a potential method for use in future studies. This work
      describes the use of TRFS to evaluate the fluorescence lifetimes of OM of whole
      soils from the Amazon region. Analysis was made of pellets of soils from an
      oxisol-spodosol system, collected in Sao Gabriel da Cachoeira (Amazonas, Brazil).
      The fluorescence lifetimes in the oxisol-spodosol system were attributed to two
      different fluorophores. One was related to complexation of an OM fraction with
      metals, resulting in a shorter fluorophore lifetime. A short fluorescence
      lifetime (2-12 ns) could be associated with simpler structures of the OM, while a
      long lifetime (19-66 ns) was associated with more complex OM structures. This new
      TRFS technique for analysis of the fluorescence lifetime in whole soil samples
      complies with the principles of green chemistry.

PMID- 29048039
TI  - Nonvolatile plasmonic holographic memory based on photo-driven ion migration.
AB  - Stability of data storage is essential for optical information processing. TiO2
      nanoporous films loaded with small-sized Ag nanoparticles thus attracted much
      attention due to their fast and polarization-sensitive photochemical response,
      which is able to realize optical phase modulation and high-density optical
      memory. However, little attention was given to the modulation of the silver ion
      migration, which plays a key role in anti-erasure of the recorded hologram. In
      this paper, the strong coupling of two phase gratings was achieved by long-term
      recording in the Ag-TiO2 film irradiated with a pair of coherent left- and right
      hand circular polarization lights from a Blu-ray (~405  nm) laser. The migration
      of Ag+ ions was enhanced by the electronic field gradient force. A stable
      polarization holographic grating was obtained by this method and observed by a
      polarizing microscope. This work provided a strategy for a nonvolatile device
      based on photo-driven ion migration.

PMID- 29048040
TI  - Compressive correlation holography.
AB  - We propose and demonstrate a compressive sensing (CS) framework for correlation
      holography. This is accomplished by adopting the principle of compressive sensing
      and thresholding in the two-point intensity correlation. The measurement matrix
      and the sensing matrix that are required for applying the CS framework here are
      systematically extracted from the random illuminations of the laser speckle data.
      Reconstruction results using CS, CS with thresholding, and intensity correlation
      are compared. Our study reveals that liminal CS requires far fewer samples for
      the reconstruction of the hologram and has wide application in image
      reconstruction.

PMID- 29048041
TI  - High-precision frequency estimation for frequency modulated continuous wave laser
      ranging using the multiple signal classification method.
AB  - The long fiber frequency sampling method is used to eliminate the nonlinearity of
      laser tuning in the frequency-modulated continuous-wave laser detection and
      ranging (FMCW ladar) technique. However, although it has high precision, it is
      affected by the picket fence effect and spectrum leakage. In this paper, we
      propose a novel frequency estimation method, multiple signal classification
      (MUSIC), to be used instead of the conventional fast Fourier transform (FFT)
      based algorithm in order to obtain better range precision. The proposed method
      was verified by experiments. In the experiments, when the distance was up to
      3.814 m and chirped bandwidth was equal to 20 nm (2.5 THz), the full width at
      half-maximum of the range peak, which represented the estimated precision of
      frequency obtained by MUSIC, was 20 MUm, and it was improved by 7 times compared
      to the FFT-based method. Meanwhile, to evaluate the performance of the proposed
      method, the frequency estimation according to the Cramer-Rao lower bound (CRLB)
      was also performed. The experimental results have shown that the mean square
      error of distance estimation based on the MUSIC algorithm is 0.56 MUm, which is
      much closer to the CRLB of 0.18 MUm than the mean square error of the
      conventional FFT-based method. Furthermore, we demonstrated that the MUSIC
      estimator has an unparalleled advantage over other estimators in the high
      precision ranging fields.

PMID- 29048042
TI  - Displacement sensing using the relaxation oscillation frequency of a laser diode
      with optical feedback.
AB  - A laser diode (LD) with external optical feedback can generate undamped
      relaxation oscillation (RO) under certain operational conditions. The RO
      frequency can be modified by the external cavity length of the LD and is highly
      sensitive to the variation of the cavity length (DeltaL). This work first
      investigates the relationship between the RO frequency and DeltaL by solving the
      well-known Lang-Kobayashi (L-K) equations and then verifies the relationship by
      experiments. Both theory and experiment show that the RO frequency changes in a
      sawtooth-like quasi-periodic manner with respect to DeltaL. The fundamental
      period is half laser wavelength. This sawtooth feature enables us to achieve
      period unwrapping and thus extend the measurement range up to a few micrometers.
      This work shows a possible new solution for achieving high-resolution, large
      range displacement measurements.

PMID- 29048043
TI  - On-demand tailored vector beams.
AB  - We introduce an effective optical system to produce optical beams with arbitrary,
      inhomogeneous polarization states. Using our system, we are capable of generating
      vector beams with discretionarily chosen transverse complex fields in a
      straightforward way. We generate several different instances of well-known vector
      beams and the less common spirally polarized vector beams, as well as a full
      Poincare beam. We visually show the continual transition between azimuthally and
      radially polarized beams via a collection of spirally polarized beams. We
      experimentally determine the polarization states of the generated beams and
      quantitatively assess the performance of our system. We find that the measured
      polarization distributions accurately coincide with the intended input
      polarization distributions.

PMID- 29048044
TI  - Scheme for achieving a continuous-wave laser operation at 1178  nm.
AB  - We report for the first time, to the best of our knowledge, a new scheme for
      generating the important 1178 nm laser. Based on a high-power 1018 nm fiber laser
      as the pump source and chemical vapor deposition diamond as the Raman gain
      medium, the Raman laser was capable of generating 34.6 W output power centered at
      1178.02 nm. As far as we know, 34.6 W is the highest output power of a 1178 nm
      laser obtained within a crystalline Raman gain medium. The experimental results
      show the superiority of our scheme in obtaining 1178 nm laser generation.

PMID- 29048045
TI  - UV laser fabrication and modification of fiber Bragg gratings by stitching sub
      gratings with in situ fluorescence monitoring.
AB  - We present a method for synthesizing complex fiber Bragg gratings using
      femtosecond UV laser pulses and image projection from a small phase mask. Fiber
      gratings with arbitrary spectral reflectivity can be achieved by stitching short
      grating segments with proper phases. The relative phase between neighboring sub
      gratings is controlled using in situ UV-excited fluorescence monitoring. During
      the fabrication, we are able to monitor the amplitude and phase of each segment
      right after it was written. This is accomplished by scanning the phase mask with
      attenuated UV laser pulses and observing modulation in fluorescence. This
      information allows us to precisely set the position of fiber for the next
      segment. A fabricated grating segment can also be effectively erased with
      additional out-of-phase UV exposure. Bragg gratings over both telecom C-band and
      L-band can be conveniently achieved with this simple setup and a single phase
      mask.

PMID- 29048046
TI  - Absolute calibration of optical streak cameras on picosecond time scales using
      supercontinuum generation.
AB  - We report a new method using high-stability, laser-driven supercontinuum
      generation in a liquid cell to calibrate the absolute photon response of fast
      optical streak cameras as a function of wavelength when operating at fastest
      sweep speeds. A stable, pulsed white light source based around the use of self
      phase modulation in a salt solution was developed to provide the required
      brightness on picosecond time scales, enabling streak camera calibration in fully
      dynamic operation. The measured spectral brightness allowed for absolute photon
      response calibration over a broad spectral range (425-650 nm). Calibrations
      performed with two Axis Photonique streak cameras using the Photonis P820PSU
      streak tube demonstrated responses that qualitatively follow the photocathode
      response. Peak sensitivities were one photon/count above background. The absolute
      dynamic sensitivity is less than the static by up to an order of magnitude. We
      attribute this to the dynamic response of the phosphor being lower.

PMID- 29048047
TI  - D-shaped photonic crystal fiber refractive index sensor based on surface plasmon
      resonance.
AB  - A type of D-shaped photonic crystal fiber sensor based on surface plasmon
      resonance (SPR) is proposed for refractive index sensing and analyzed by the
      finite element method. The SPR effect between surface plasmon polariton modes and
      fiber core modes of the designed D-shaped photonic crystal fiber is used to
      measure the refractive index of the analyte. Numerical results show that the
      sensor can detect a range of refractive index ranging from 1.33 to 1.38. When the
      thickness of metal film is t=20  nm, the maximum sensitivity of 10,493  nm/RIU is
      obtained with a very high resolution of 9.53*10-6  RIU. The good sensing
      performance makes the proposed sensor a competitive candidate for environmental,
      biological, and biochemical sensing applications.

PMID- 29048048
TI  - Design and numerical analysis of a THz square porous-core photonic crystal fiber
      for low flattened dispersion, ultrahigh birefringence.
AB  - We propose a kind of square porous-core photonic crystal fiber (PCF) for
      polarization-maintaining terahertz (THz) wave guidance. An asymmetry is
      introduced by implementing rectangular array air holes in the porous core of the
      PCF, and ultrahigh birefringence and low effective material loss (EML) can be
      achieved simultaneously. The properties of THz wave propagation are analyzed
      numerically in detail. The numerical results indicate that the proposed fiber
      offers a high birefringence of 0.063 and a low EML of 0.081  cm-1 at 1 THz.
      Moreover, a very low flattened dispersion profile is observed over a wide
      frequency domain of 0.85-1.9 THz. The zero flattened dispersion can be
      controlled. It is predicted that this PCF would be used potentially in
      polarization maintaining and dispersion management of THz waves.

PMID- 29048049
TI  - Bike ride, solar eclipse, and back to school: editorial.
AB  - Editor-in-Chief Ron Driggers shares a recent adventure, encourages readers to
      experience the upcoming total solar eclipse in the U.S., and announces that he
      has accepted a faculty position.

PMID- 29048050
TI  - Compact fabrication-tolerant subwavelength-grating-based two-mode division
      (de)multiplexer.
AB  - Regarding the importance of bandwidth and capacity expansion in communication
      systems, a novel mode division (de)multiplexer based on subwavelength grating
      (SWG) is proposed. SWG-based devices could have smaller sizes, be much more
      fabrication-tolerant, and have much wider bandwidths due to the reduced
      confinement of the field and dispersion. It is also feasible to reduce the loss
      of a SWG-based device by tuning the duty cycle of the grating. Owing to these
      properties of SWGs, we have designed a compact fabrication-tolerant two-mode
      division (de)multiplexer. A flat-top transmission of >0.89 (loss <0.5  dB) is
      obtained over 65 nm from 1500 to 1565 nm, completely covering the entire C-band
      used for dense wavelength division multiplexing. Moreover, the cross-talk is <-10
      dB for a broad bandwidth of ~120  nm over which the loss of the complete device
      including both multiplexer and demultiplexer is <1  dB. Therefore, the proposed
      device is promising for high-capacity optical communications in both conventional
      and entirely SWG-based silicon photonic circuits.

PMID- 29048051
TI  - Negative influence of detector noise on ghost imaging based on the photon
      counting technique at low light levels.
AB  - The influence of detector noise on ghost imaging (GI) is investigated at low
      light levels. Based on the characteristics of the additive detector noise, we
      establish the analytical model and display the ghost images through numerical and
      experimental demonstrations. It is shown that the contrast-to-noise ratio and
      visibility of reconstructed images are sharply affected by the detector noise.
      Following the increase of the ratio of average signal intensity to the average
      noise, the quality of reconstructions is enhanced. To reduce the measurement
      numbers and, thus, shorten the consuming time without sacrificing the imaging
      quality, we propose a sorting technique in the traditional GI algorithm for a
      high quality image reconstruction. The results demonstrated here will be
      favorable to the applications of low-light-level imaging.

PMID- 29048053
TI  - Analysis and investigation of temperature and hydrostatic pressure effects on
      optical characteristics of multiple quantum well slow light devices.
AB  - This paper represents the influences of temperature and hydrostatic pressure
      variations on GaAs/AlGaAs multiple quantum well slow light systems based on
      coherence population oscillations. An analytical model in non-integer dimension
      space is used to study the considerable effects of these parameters on optical
      properties of the slow light apparatus. Exciton oscillator strength and
      fractional dimension constants have special roles on the analytical model in
      fractional dimension. Hence, the impacts of hydrostatic pressure and temperature
      on exciton oscillator strength and fractional dimension quantity are investigated
      theoretically in this paper. Based on the achieved results, temperature and
      hydrostatic pressure play key roles on optical parameters of the slow light
      systems, such as the slow down factor and central energy of the device. It is
      found that the slope and value of the refractive index real part change with
      alterations of temperature and hydrostatic pressure in the range of 5-40 deg of
      Kelvin and 1 bar to 2 kbar, respectively. Thus, the peak value of the slow down
      factor can be adjusted by altering these parameters. Moreover, the central energy
      of the device shifts when the hydrostatic pressure is applied to the slow light
      device or temperature is varied. In comparison with previous reported
      experimental results, our simulations follow them successfully. It is shown that
      the maximum value of the slow down factor is estimated close to 5.5*104 with a
      fine adjustment of temperature and hydrostatic pressure. Meanwhile, the central
      energy shift of the slow light device rises up to 27 meV, which provides an
      appropriate basis for different optical devices in which multiple quantum well
      slow light is one of their essential subsections. This multiple quantum well slow
      light device has potential applications for use as a tunable optical buffer and
      pressure/temperature sensors.

PMID- 29048052
TI  - Convolutional neural network-based data page classification for holographic
      memory.
AB  - We propose a deep-learning-based classification of data pages used in holographic
      memory. We numerically investigated the classification performance of a
      conventional multilayer perceptron (MLP) and a deep neural network, under the
      condition that reconstructed page data are contaminated by some noise and are
      randomly laterally shifted. When data pages are randomly laterally shifted, the
      MLP was found to have a classification accuracy of 93.02%, whereas the deep
      neural network was able to classify data pages at an accuracy of 99.98%. The
      accuracy of the deep neural network is 2 orders of magnitude better than the MLP.

PMID- 29048054
TI  - Coherent laser phase retrieval in the presence of measurement imperfections and
      incoherent light.
AB  - Phase retrieval is a powerful numerical method that can be used to determine the
      wavefront of laser beams based only on intensity measurements, without the use of
      expensive, low-resolution specialized wavefront sensors such as Shack-Hartmann
      sensors. However, phase retrieval techniques generally suffer from poor
      convergence and fidelity when the input measurements contain electronic or
      optical noise and/or an incoherent intensity contribution overlapped with the
      otherwise spatially coherent laser beam. Here, we present an implementation of a
      modified version of the standard multiple-plane Gerchberg-Saxton algorithm and
      demonstrate that it is highly successful at extracting the intensity profile and
      wavefront of the spatially coherent part of the light from various lasers,
      including tapered laser diodes, at a very high fidelity despite the presence of
      incoherent light and noise.

PMID- 29048055
TI  - Automated batch characterization of inkjet-printed elastomer lenses using a LEGO
      platform.
AB  - Small, self-adhesive, inkjet-printed elastomer lenses have enabled smartphone
      cameras to image and resolve microscopic objects. However, the performance of
      different lenses within a batch is affected by hard-to-control environmental
      variables. We present a cost-effective platform to perform automated batch
      characterization of 300 lens units simultaneously for quality inspection. The
      system was designed and configured with LEGO bricks, 3D printed parts, and a
      digital camera. The scheme presented here may become the basis of a high
      throughput, in-line inspection tool for quality control purposes and can also be
      employed for optimization of the manufacturing process.

PMID- 29048056
TI  - Reversible and irreversible alterations of the optical thickness of PQ/PMMA
      volume recording media samples. Part I: Experiment.
AB  - Experimental research into changes of the optical thickness of
      phenanthrenequinone-doped polymethyl methacrylate samples in the process of
      irradiation by a 473 nm laser is presented. It was demonstrated that heating
      induced reversible changes lead to a decrease in the optical thickness. The
      temperature coefficient of the relative changes of the optical thickness was
      measured to be -1.40*10-5  K-1, which matches the data published by other
      authors. It is also established that the irreversible changes induced by the
      photochemical transformation lead to an increase in the optical thickness outside
      of the absorption band of the samples (lambda>530  nm), where the relative change
      of which at lambda=532  nm is +3.7*10-5. It was demonstrated that the reversible
      and irreversible changes do not compensate for each other in the process of
      sample exposure.

PMID- 29048057
TI  - Improvement of pointing accuracy for Risley prisms by parameter identification.
AB  - Risley prisms appear to be a promising solution to high-accuracy pointing and
      tracking. To improve the pointing accuracy of achromatic Risley prisms, an
      appropriate mathematical model is established, and the forward and inverse
      solutions are proposed. Focusing on the sources of systematic errors, an
      optimization method based on a genetic algorithm is proposed to identify the
      parameters of the physical model, including wedge angles, refractive indexes, and
      installations. Finally, the experimental platform is established. The pointing
      accuracy and the size of the blind zone are tested to prove the validity of the
      method. Experimental results show that the proposed method is effective to reduce
      the influence of manufacturing, installation, and measurement errors. The
      optimized pointing accuracy has been improved significantly. Within the maximum
      deflection angle of 3 degrees , the maximum pointing error is reduced from 33
      arcsec to less than 1 arcsec. And the angular dynamic range is found to be
      greater than 43 dB, able to meet the needs of the majority of applications. In
      addition, the test of the blind zone shows that the optimized parameters are
      consistent with the actual system.

PMID- 29048058
TI  - Extra-cavity radiofrequency modulator for a lidar radar designed for underwater
      target detection.
AB  - The hybrid lidar-radar technique is commonly used for shallow underwater target
      detection. This technique requires a powerful blue-green RF-modulated laser with
      stable microwave frequency. In this paper, a novel modulator design perfectly
      suited for this application is proposed. It consists of an extra-cavity modulator
      composed of two plane mirrors and a second-harmonic generator stage within the
      cavity to maximize the energy efficiency. This modulator is coupled with a
      picosecond Nd:YAG infrared laser source to insure the emission of a powerful
      pulse (up to 5 mJ). Results considering this architecture show stable modulation
      frequency and a powerful modulated beam. As the emitted signal lasts only a few
      nanoseconds, a range-gating method can be used for target localization. This
      emitted signal has experimentally proven to preserve input beam polarization,
      which also can be employed to enhance the target return.

PMID- 29048059
TI  - Optomechanical design of rotary kaleidoscope for bidirectional texture function
      acquisition.
AB  - Optical systems are traditionally used for accurate recording and measurement of
      the real world's appearance. Present techniques allow us to form a computer-based
      virtual world, which is used in a variety of technical fields. The crucial issue
      for future applications of virtual reality is the fidelity of rendered images to
      real-world objects. This is strongly affected by the appearance of the rendered
      object's surfaces. Currently, the most applied method of describing a surface's
      visual appearance of spatially nonuniform surfaces is bidirectional texture
      function (BTF). We have designed, optimized, built, and tested a unique portable
      instrument based on a rotary kaleidoscope principle for BTF acquisition in situ.
      To the best of our knowledge, such an instrument has never been used before to
      measure BTF of a surface. We enhanced a common static kaleidoscope by adding
      rotation, which allows us to get a larger number of images of the sample for more
      combinations of illumination directions and viewing directions. This results in a
      higher directional and spatial resolution of measured BTF data. In this paper, we
      focus on the optomechanical design of the rotary BTF measurement instrument and
      issues related to its alignment to keep the desired mechanical precision.

PMID- 29048060
TI  - Instantaneous 3D imaging of highly turbulent flames using computed tomography of
      chemiluminescence.
AB  - The computed tomography of chemiluminescence (CTC) technique was applied for the
      first time to a real highly turbulent swirl flame setup, using a large number of
      CCD cameras (Nq=24 views), to directly reconstruct the three-dimensional
      instantaneous and time-averaged chemiluminescence fields. The views were obtained
      from a 172.5 degrees  region (in one plane) around the flame, and the CTC
      algorithm [Floyd et al., Combust. Flame158, 376 (2011)CBFMAO0010-2180] was used
      to reconstruct the flame by discretizing the domain into voxels. We investigated
      how the reconstructions are affected by the views' arrangement and the settings
      of the algorithm, and considered how the quality of reconstructions should be
      assessed to ensure a realistic description of the capabilities of the technique.
      Reconstructions using Nq<=12 were generally better when the cameras were
      distributed more equiangularly. When Nq was severely low (e.g., 3), the
      reconstruction could be improved by using fewer voxels. The paper concludes with
      a summary of the strengths and weaknesses of the CTC technique for examining a
      real turbulent flame geometry and provides guidance on best practice.

PMID- 29048061
TI  - Wavefront aberration metrology based on transmitted fringe deflectometry.
AB  - A simple, precise, and innovative technique for wavefront aberration measurement
      is presented in this paper. This technique is based on transmitted fringe
      deflectometry (TFD) used to measure wavefront slope and wavefronts. The system
      measurement error when measuring wavefront aberration is analyzed, including the
      aberration of the reference wavefront caused by shape distribution and the tilt
      and decentration of the phase object. Based on this, the system error model is
      established, and the system error compensation method is also presented. In
      addition, the system parameters calibration method is discussed in detail.
      Simulation and experimental results show that the proposed TFD wavefront
      aberration measurement model can achieve high measurement accuracy.

PMID- 29048062
TI  - Ductile mode grinding of reaction-bonded silicon carbide mirrors.
AB  - The demand for reaction-bonded silicon carbide (RB-SiC) mirrors has escalated
      recently with the rapid development of space optical remote sensors used in
      astronomy or Earth observation. However, RB-SiC is difficult to machine due to
      its high hardness. This study intends to perform ductile mode grinding to RB-SiC,
      which produces superior surface integrity and fewer subsurface damages, thus
      minimizing the workload of subsequent lapping and polishing. For this purpose, a
      modified theoretical model for grain depth of cut of grinding wheels is
      presented, which correlates various processing parameters and the material
      characteristics (i.e., elastic module) of a wheel's bonding matrix and workpiece.
      Ductile mode grinding can be achieved as the grain depth of cut of wheels
      decreases to be less than the critical cut depth of workpieces. The theoretical
      model gives a roadmap to optimize the grinding parameters for ductile mode
      grinding of RB-SiC and other ultra-hard brittle materials. Its feasibility was
      validated by experiments. With the optimized grinding parameters for RB-SiC, the
      ductile mode grinding produced highly specular surfaces (with roughness of ~2.2
      2.8  nm Ra), which means the material removal mechanism of RB-SiC is dominated by
      plastic deformation rather than brittle fracture. Contrast experiments were also
      conducted on fused silica, using the same grinding parameters; this produced only
      very rough surfaces, which further validated the feasibility of the proposed
      model.

PMID- 29048063
TI  - Determination of laser beam focus position based on secondary speckles pattern
      analysis.
AB  - Proper positioning of a laser beam focus is a universal problem for various
      applications that does not have a universal solution. Quite often the taken
      approach relies on some sort of a calibration and temporal stability of the laser
      and the optical train. While such an approach can be suitable for a large number
      of applications its applicability becomes limited in the cases where the laser
      beam properties uncontrollably change with time. The latter can occur due to the
      thermal effects, for example. In those cases, the laser focus positioning method
      should include direct analysis of the laser beam properties. In this contribution
      we present a simple optical method based on the secondary speckles pattern
      analysis suitable for determination of the absolute focal spot position. The
      method does not require any a priori knowledge of the laser beam properties and
      is suitable for various diffuse or partially diffuse surfaces of interest.

PMID- 29048065
TI  - Investigation of nonuniform surface properties of classically manufactured fused
      silica windows.
AB  - We report on investigations of the spatial variations of contamination,
      roughness, and index of refraction of classically manufactured polished fused
      silica surfaces. Therefore, laser-induced breakdown spectroscopy was used to
      probe surface and subsurface impurities via the detection of aluminum.
      Measurements at different positions on the surface of the cylindrical fused
      silica windows evidenced an almost contamination-free center region, whereas a
      relatively large contamination area was found close to the edge. In-depth
      measurements verify the presence of aluminum atoms in the bulk until a depth of
      several tens of microns for the edge region. In addition, atomic force
      microscopic measurements show that the surface roughness is larger in the center
      region compared to the edge. Further, the index of refraction increases from the
      center region towards the edge as measured via ellipsometry. The results indicate
      a nonuniform impact of the grinding, lapping, and polishing tools on the surface.
      The findings turn out to be of specific interest for different applications,
      particularly for the realization of large-scale high-performance coatings.

PMID- 29048064
TI  - Triple Brillouin frequency spacing multiwavelength fiber laser with double
      Brillouin cavities and its application in microwave signal generation.
AB  - We propose and experimentally investigate a multiwavelength Brillouin fiber laser
      (MBFL) with triple frequency spacing by employing a modular structure. In this
      scheme, we obtain nine channels optimized with frequency spacing of 0.259 nm. The
      single, double, and triple Brillouin frequency spacing for the MBFL can be easily
      realized by utilizing this modular structure. The impact of Brillouin pump (BP)
      power, BP wavelength, and erbium-ytterbium-doped fiber amplifier (EYDFA) output
      power on the performance of the MBFL is investigated, respectively. We also study
      the generation of beating frequency microwave signals based on single, double,
      and triple frequency spacing MBFL. 10.5 GHz, 21.48 GHz, and 31.77 GHz microwave
      signals with 3 dB linewidth of 16.4 MHz, 15.2 MHz, and 12.8 MHz are generated,
      respectively.

PMID- 29048066
TI  - Defect detection based on a lensless reflective point diffraction interferometer.
AB  - We propose a defect detection system to identify phase defects on optics based on
      a lensless reflective point diffraction interferometer (LRPDI). The optics under
      test are illuminated by a collimated beam to produce a signal wavefront carrying
      the defect information, and then the signal wavefront is recorded in a high
      carrier interferogram using the LRPDI. By lensless imaging, amplitude and phase
      defects, as well as the accurate phase of a phase defect, can be identified. The
      simulation and experiment demonstrate the success of the proposed system in
      detecting phase defects, and its high-accuracy and high-resolution dynamic
      detection abilities are verified.

PMID- 29048067
TI  - Design and simulation of a superposition compound eye system based on hybrid
      diffractive-refractive lenses.
AB  - Compound eyes offer a promising field of miniaturized imaging systems. In one
      application of a compound eye, superposition of compound eye systems forms a
      composite image by superposing the images produced by different channels. The
      geometric configuration of superposition compound eye systems is achieved by
      three micro-lens arrays with different pitches and focal lengths. High resolution
      is indispensable for the practicability of superposition compound eye systems. In
      this paper, hybrid diffractive-refractive lenses are introduced into the design
      of a compound eye system for this purpose. With the help of ZEMAX, two
      superposition compound eye systems with and without hybrid diffractive-refractive
      lenses were separately designed. Then, we demonstrate the effectiveness of using
      a hybrid diffractive-refractive lens to improve the image quality.

PMID- 29048068
TI  - Demodulation algorithm for optical fiber F-P sensor.
AB  - The demodulation algorithm is very important to improving the measurement
      accuracy of a sensing system. In this paper, the variable step size hill climbing
      search method will be initially used for the optical fiber Fabry-Perot (F-P)
      sensing demodulation algorithm. Compared with the traditional discrete gap
      transformation demodulation algorithm, the computation is greatly reduced by
      changing step size of each climb, which could achieve nano-scale resolution, high
      measurement accuracy, high demodulation rates, and large dynamic demodulation
      range. An optical fiber F-P pressure sensor based on micro-electro-mechanical
      system (MEMS) has been fabricated to carry out the experiment, and the results
      show that the resolution of the algorithm can reach nano-scale level, the
      sensor's sensitivity is about 2.5  nm/KPa, which is similar to the theoretical
      value, and this sensor has great reproducibility.

PMID- 29048069
TI  - Optical system design of an atmospheric detector with nadir view and
      omnidirectional limb view.
AB  - A new type of optical system for atmospheric detection is designed by using the
      principle of panoramic imaging. Compared to the traditional ones, this optical
      system can observe nadir view and omnidirectional limb view at the same time,
      thus improving the efficiency and accuracy of the observation data inversion. The
      optical system consists of a front lens group, a panoramic annular lens, a relay
      lens group, and a narrowband filter. The nadir view and limb view are shared with
      the panoramic annular lens and the relay lens group. The narrowband filter is
      employed to select the specific band and restrain the stray light outside the
      band. This detector can monitor atmosphere conditions in the nadir field of view
      of 10 degrees  and the limb field of view of 360 degrees *(70.9 degrees -73.3
      degrees ). Based on this optical design, we develop a prototype for the detector
      and use it for the field test. The results of experiments verify the feasibility
      of the optical system design.

PMID- 29048070
TI  - Low-stress and high-reflectance Mo/Si multilayers for extreme ultraviolet
      lithography by magnetron sputtering deposition with bias assistance.
AB  - To explore the potential of achieving low-stress and high-reflectance Mo/Si
      multilayers deposited by conventional magnetron sputtering with bias assistance,
      we investigated the effects of varying Ar gas pressure, substrate bias voltage,
      and a bias-assisted Si ratio on the stress and extreme ultraviolet (EUV)
      reflectance of Mo/Si multilayers. To reduce the damage of ion bombardments on an
      Si-on-Mo interface, only the final part of the Si layer was deposited with bias
      assistance. Bias voltage has strong influence on the stress. The compressive
      stress of Mo/Si multilayers can be reduced remarkably by increasing bias voltage
      due to the increase of Mo-on-Si interdiffusion and postponement of Mo
      crystallization transition. Properly choosing gas pressure and a bias-assisted Si
      ratio is critical to obtain high EUV reflectance. Appropriately decreasing gas
      pressure can reduce the interface roughness without increasing interdiffusion.
      Too much bias assistance can seriously reduce the optical contrast between Mo and
      Si layers and lead to a remarkable decrease of EUV reflectance. Thus, by
      appropriately choosing gas pressure, bias voltage, and a bias-assisted Si ratio,
      the stress values of Mo/Si multilayers can be reduced to the order of -100  MPa
      with an EUV reflectance loss of about 1%.

PMID- 29048071
TI  - 2  MUm laser oscillation of Ho3+:Tm3+-codoped silica microspheres.
AB  - 2 MUm laser oscillation with a low threshold has been achieved in Ho3+:Tm3+
      codoped silica microspheres (HTCSMs). Ho3+:Tm3+-codoped solgel functionalization
      film is applied to the surface of a silica microsphere, and an optical tapered
      fiber is adopted to couple an 808 nm continuous-wave laser to serve as the pump
      light source. Multimode and single-mode laser oscillations around 2 MUm within
      the eye-safe wave band are observed due to the I75->I85 transitions of Ho3+ ions
      sensitized by Tm3+. The morphology characteristics of microspheres determine the
      multimode laser oscillation spectrum. The free spectral range is in good
      accordance with the calculated value based on Mie scattering theory. The HTCSM
      laser oscillation shows characteristics of good capability, simple process, high
      flexibility, and low cost.

PMID- 29048072
TI  - Wave-optics simulation of the double-pass beam propagation in modulating retro
      reflector FSO systems using a corner cube reflector.
AB  - Free-space optical (FSO) communication utilizing a modulating retro-reflector
      (MRR) is an innovative way to convey information between the traditional optical
      transceiver and the semi-passive MRR unit that reflects optical signals. The
      reflected signals experience turbulence-induced fading in the double-pass
      channel, which is very different from that in the traditional single-pass FSO
      channel. In this paper, we consider the corner cube reflector (CCR) as the retro
      reflective device in the MRR. A general geometrical model of the CCR is
      established based on the ray tracing method to describe the ray trajectory inside
      the CCR. This ray tracing model could treat the general case that the optical
      beam is obliquely incident on the hypotenuse surface of the CCR with the dihedral
      angle error and surface nonflatness. Then, we integrate this general CCR model
      into the wave-optics (WO) simulation to construct the double-pass beam
      propagation simulation. This double-pass simulation contains the forward
      propagation from the transceiver to the MRR through the atmosphere, the retro
      reflection of the CCR, and the backward propagation from the MRR to the
      transceiver, which can be realized by a single-pass WO simulation, the ray
      tracing CCR model, and another single-pass WO simulation, respectively. To verify
      the proposed CCR model and double-pass WO simulation, the effective reflection
      area, the incremental phase, and the reflected beam spot on the transceiver plane
      of the CCR are analyzed, and the numerical results are in agreement with the
      previously published results. Finally, we use the double-pass WO simulation to
      investigate the double-pass channel in the MRR FSO systems. The histograms of the
      turbulence-induced fading in the forward and backward channels are obtained from
      the simulation data and are fitted by gamma-gamma (GammaGamma) distributions. As
      the two opposite channels are highly correlated, we model the double-pass channel
      fading by the product of two correlated GammaGamma random variables (RVs).

PMID- 29048073
TI  - Effective mode-field diameter for few-mode fibers for considering splice loss
      characteristics.
AB  - We experimentally and numerically investigate the applicability of the
      conventional near-field pattern, far-field pattern (FFP), and variable aperture
      (VA) methods for measuring the effective mode-field diameter (MFD) of the higher
      order modes, which can be used for accurately evaluating splice loss. We
      confirmed that the variation in the MFD values obtained with the FFP and VA
      methods can be converged by considering the minimum scanning angle and the
      minimum aperture angle, respectively, for both fundamental and higher-order
      modes. We reveal that the FFP and VA methods provide adequate effective MFD
      values for few-mode fiber (FMF), which can be used for evaluating the splice loss
      based on the conventional Gaussian fitting model. We also show the applicability
      of the effective MFD to four linearly polarized mode FMFs for considering the
      splice loss characteristics of each mode.

PMID- 29048074
TI  - Effective method for fast and detailed analysis of holographic patterns over a
      large area.
AB  - An effective method is proposed that enables one to simultaneously analyze
      details of numerous holographic grating patterns over a large area. Unlike the
      conventional approaches relying on sophisticated lighting and optical systems and
      dark environment, only a flatbed scanner is needed. Thanks to the "rotate-scan"
      measurement strategy, details of the holographic grating patterns can be
      obtained, e.g., spatial distribution of the grating patterns, interval and
      orientation of the grating grooves within each grating pattern, and defects of
      the holographic patterns. The method has been verified by applications to two
      holographic papers of different grating intervals and orientations. The measured
      values agree well with those obtained with a light optical microscope (LOM). The
      proposed method is applicable to both transparent and reflective holographic
      materials of broad grating periodicity.

PMID- 29048075
TI  - Fluorescence properties of doxorubicin coupled carbon nanocarriers.
AB  - The effect of graphene oxide (GO) and nanodiamond (ND) is investigated on the
      spectral properties of doxorubicin (DOX) fluorescence emissions in the form of
      (DOX+GO) and (DOX+ND) biomaterials. It is shown that carbon nanostructure
      additives lead to sensible blueshifts, due to their optical properties and
      surface functionality. The quenching coefficient KND is obtained to be KND=0.043 
      (MUg/ml)-1 and KGO=0.342  (MUg/ml)-1 in DOX solutions. In general, Stern-Volmer
      attests that excited (DOX+GO) strongly quenches with respect to that of (DOX+ND)
      regarding its privileged bonding affinity.

PMID- 29048076
TI  - Nickel-catalyzed acetamidation and lactamization of arylboronic acids.
AB  - A nickel-catalyzed acetamidation and lactamization of arylboronic acids via a one
      pot reaction with ynamides and N-hydroxyphthalimide is described. This protocol
      features with mild reaction conditions and a broad substrate scope, and has been
      successfully applied to late-stage functionalization of pharmaceuticals.
      Moreover, control reactions were conducted to elucidate a plausible mechanism.

PMID- 29048081
TI  - Influence of size, shape, heteroatom content and dispersive contributions on
      guest binding in a coordination cage.
AB  - A halide-triggered metallosupramolecular host was systematically studied for the
      uptake of small neutral molecules using NMR and MS experiments. Starting from
      benzene, cyclic guests were screened with respect to size (ring count), shape
      (flatness, 3D structure, substitution pattern, flexibility) and hetero atom
      content (number, position, donor character). 5-Rings and substituted 5/6-rings
      bind only weakly, while oversized (e.g. naphthalene, adamantane, ferrocene) and
      linear alkanes do not bind at all. Bridged 6-rings of the norbornane type and in
      particular DABCO bind strongly, likewise other guests with oppositely arranged
      hetero atoms. For the DABCO complex, a single crystal X-ray structure was
      obtained. The contribution of dispersive interactions to binding was derived from
      electronic structure calculations. Together, experimental and theoretical data
      deepen the understanding of guest selectivity and encapsulation driving force
      towards application of the host as a switchable receptor and reaction chamber.

PMID- 29048082
TI  - High temperature ferroelectric behaviour in alpha-MnO2 nanorods realised through
      enriched oxygen vacancy induced non-stoichiometry.
AB  - Nanostructuring followed by incorporation of defect induced non-stoichiometry is
      an emerging field of prominence due to its capacity to introduce unprecedented
      properties in materials with potential applications. In this work, crystalline
      alpha-MnO2 nanorods are synthesised using a facile co-precipitation method to
      exhibit ferroelectric behaviour for the first time. The evolution mechanism of
      the nanorods is investigated using XRD, HRTEM and FTIR spectra, while their
      thermal stability is probed using TGA/DTA. The novel properties observed are the
      result of structural rearrangements sparked by electrons in mixed valence cations
      (Mn3+/Mn4+). The high density of Jahn-Teller active Mn3+ cations breaks the
      inversion symmetry in alpha-MnO2, thereby altering the atomic environment
      inducing distortion in the basic MnO6 octahedra. Since variable temperature XRD
      analysis confirms the phase stability of the crystal structure up to very high
      temperatures, the ferroelectric phase exhibited by the material below Tc is an
      outcome of the combined effects of orbital ordering (OO) of the eg electron in
      Mn3+ and charge ordering (CO) of Mn3+ and Mn4+ cations. This is confirmed by DSC
      analysis. The breakdown of the ferroelectric nature is identified to originate as
      a result of octahedral tilting as suggested by temperature-dependent Raman
      studies. Magnetic and electrical transport studies provide additional evidence of
      a CO ferroelectric phase as they predict the existence of double-exchange hopping
      conduction and surface ferromagnetism in the sample.

PMID- 29048083
TI  - Phases and thermoelectric properties of SnTe with (Ge, Mn) co-doping.
AB  - A lead-free SnTe compound shows good electrical properties but also high thermal
      conductivity, resulting in a low figure of merit ZT. We demonstrate a significant
      enhancement of the thermoelectric properties of SnTe by (Ge, Mn) co-doping. (Ge,
      Mn) co-doped samples (Sn0.8Ge0.2)1-xMnxTe with x = 0, 0.03, 0.06, 0.09, 0.12,
      0.15, 0.18 and 0.2 were prepared for this investigation. The substitution of Ge
      for Sn in SnTe promotes the solubility of Mn in a SnTe-based phase up to 20 at%,
      which further enlarges the band gap and gives rise to enhanced valence band
      convergence as compared with Mn doping, leading to a notably increased Seebeck
      coefficient and a power factor. All alloys retain p-type conduction and hole
      carrier concentration increases with increasing Mn content. The solute Ge and Mn
      atoms as well as the second phase of Ge in a SnTe-based system enhance phonon
      scattering and thus reduce thermal conductivity. The synergistic role that Ge and
      Mn play in regulating the electron and phonon transport of SnTe yields a maximum
      figure of merit ZT of 1.22 at 873 K for the sample (Sn0.8Ge0.2)0.85Mn0.15Te.

PMID- 29048084
TI  - Thermal evolution of MnxOy nanofibres as catalysts for the oxygen reduction
      reaction.
AB  - Manganese oxides (MnxOy) are considered as a promising catalyst alternative to
      platinum in fuel cell applications. In fact, a proper catalyst is needed in order
      to facilitate the oxygen reduction reaction (ORR) at the cathode, and platinum is
      considered the best material due to its low overpotential for this reaction.
      Contrary to platinum, MnxOy is inexpensive, environmentally friendly and can be
      shaped into several nanostructures; furthermore, most of them show significant
      electro-catalytic performance. Several strategies have been carried out in order
      to increase their efficiency, by preparing light and high-surface area materials.
      In this framework, nanofibres are among the most promising nanostructures that
      can be used for this purpose. In this work, a study of the thermal, morphological
      and catalytic behavior of MnxOy nanofibres obtained through the electrospinning
      technique is proposed. Emphasis is given to the thermal evolution of the
      precursors, proposing a possible crystallization mechanism of the different
      manganese oxides obtained. It turns out that manganese oxide nanofibres exhibit
      good catalytic performance for the ORR, comparable to those obtained by using Pt
      based catalysts.

PMID- 29048085
TI  - Solution-processed indium oxide electron transporting layers for high-performance
      and photo-stable perovskite and organic solar cells.
AB  - Interface engineering is considered the key to improving the device performance
      and stability of solar cells. In particular, TiO2 nanostructures, when used as
      electron transporting layers (ETLs) in metal halide perovskite solar cells
      (PSCs), led to excellent power conversion efficiencies (PCEs) of over 20%. They
      effectively transferred charge carriers from the perovskite and suppressed charge
      recombination at the interfaces. However, the photocatalytic effect of TiO2 on
      the perovskite can significantly degrade the device performance under ultraviolet
      illumination. Therefore, other classes of n-type metal oxides with a wide band
      gap should be developed to improve their photo-stability. Herein, we demonstrate
      the development of In2O3 thin films by a solution process and their application
      as ETLs in PSCs and organic solar cells (OSCs). Pin hole-free In2O3 ETLs obtained
      by the thermal decomposition of an In precursor thin film exhibit high
      conductivity (2.49 * 10-4 S cm-1) and low surface roughness (7.33 nm). This leads
      to impressive PCEs of 14.63% and 3.03% for the PSC and the inverted OSC,
      respectively. Furthermore, the In2O3-PSC shows better photo-stability than the
      TiO2-PSC by virtue of the wider band gap of In2O3, which leads to a PCE retention
      of 74% and 46%, relative to the initial PCE values of the PSC and the inverted
      OSC, respectively.

PMID- 29048086
TI  - Oleylamine-functionalized graphene oxide as an electron block layer towards high
      performance and photostable fullerene-free polymer solar cells.
AB  - Oleylamine-functionalized graphene oxide (GO) has a shallower energy level of
      conduction band (ECB) and a deeper energy level of the valence band (EVB) as
      compared to common hole extraction layer (HEL) materials, which make the electron
      block layer (EBL). Photoluminescence, X-ray photoelectron spectroscopy (XPS), and
      current density-voltage (J-V) curves with a large reverse bias voltage range
      obtained under dark conditions are used to determine whether GO layers play
      important roles in blocking the electron transport to the MoO3/Ag composite anode
      and prevent MoO3 diffusion into a photoactive layer under light illumination.
      Moreover, GO inserted between a photoactive layer and an HEL enhances charge
      carrier transport and collection and avoids the monomolecular recombination
      between the photoactive layer and HEL. Photovoltaic parameters and photostability
      measurements of inverted and forward PSCs have shown that upon introduction of
      GO, the performance and photostability of PSCs are improved. On adding GO to
      PSCs, the power conversion efficiency (PCE) increases approximately 5% and 4% and
      reduces the decay ratio to approximately 50% and 65% of the initial value for the
      inverted and forward PSCs, respectively.

PMID- 29048087
TI  - A diversity oriented synthesis of natural product inspired molecular libraries.
AB  - Natural products are the source of innumerable pharmaceutical drug candidates and
      also form an important aspect of herbal remedies. They are also a source of
      various bioactive compounds. Herein we have leveraged the structural attributes
      of several natural products in building a library of architecturally diverse
      chiral molecules by harnessing R-tryptophan as the chiral auxiliary. It is
      converted to its corresponding methyl ester 1 which in turn provided a bevy of 1
      aryl-tetrahydro-beta-carbolines 2a-d, which were then converted to chiral
      compounds via a diversity oriented synthetic strategy (DOS). In general,
      intermolecular and intramolecular ring rearrangements facilitated the formation
      of the final compounds. Four different classes of molecules with distinct
      architectures were generated, adding up to nearly twenty-two individual
      molecules. Phenotypic screening of a representative section of the library
      revealed two molecules that selectively inhibit MCF7 breast cancer cells with
      IC50 of ~5 MUg mL-1 potency.

PMID- 29048089
TI  - Reversible pressure pre-amorphization of a piezochromic metal-organic framework.
AB  - The piezochromic metal-organic framework Co2(Bdc)2Dabco.4DMF.H2O (Bdc denotes 1,4
      benzenedicarboxylate, Dabco - 1,4-diazabicyclo[2.2.2]octane, and DMF -
      dimethylformamide) under ambient conditions is tetragonal (phase alpha) and at
      about 1.9 GPa undergoes a strong pressure-induced shortening of translational
      correlations in the sample. A broad gradual pre-amorphization process starting at
      about 0.7 GPa reduces the tetragonal symmetry and is described as phase beta. The
      pre-amorphization mechanism involves several competing distortions of the Bdc
      linkers and Co(ii)-coordination schemes. These in turn, affect the crystal field
      around the cations and their optical absorption. The compression strongly affects
      the VIS absorption of this piezochromic compound visibly changing its colour from
      blue to red.

PMID- 29048088
TI  - Synthesis, characterization and biological activity of new cyclometallated
      platinum(iv) iodido complexes.
AB  - The synthesis of six novel cyclometallated platinum(iv) iodido complexes is
      accomplished by intermolecular oxidative addition of methyl iodide (compounds 2a
      2c) or iodine (compounds 3a-3c) upon cyclometallated platinum(ii) compounds
      [PtX{(CH3)2N(CH2)3NCH(4-ClC6H3)}] (1a-1c: X = Cl, CH3 or I). The X-ray molecular
      structures of platinum(ii) compound 1c and platinum(iv) compounds 3b and 3a' (an
      isomer of 3a) are reported. The cytotoxic activity against a panel of human
      adenocarcinoma cell lines (A-549 lung, MDA-MB-231 and MCF-7 breast, and HCT-116
      colon), DNA interaction, topoisomerase I, IIalpha, and cathepsin B inhibition,
      and cell cycle arrest, apoptosis and ROS generation of the investigated complexes
      are presented. Remarkable antiproliferative activity was observed for most of the
      synthesized cycloplatinated compounds (series 1-3) in all the selected carcinoma
      cell lines. The best inhibition was provided for the octahedral platinum(iv)
      compounds 2a-2c exhibiting a methyl and an iodido axial ligand. Preliminary
      biological results point to a different mechanism of action for the investigated
      compounds. Cyclometallated platinum(ii) compounds 1a-1c modify the DNA migration
      as cisplatin. In contrast, cyclometallated platinum(iv) compounds 2a-2c and 3a-3c
      did not modify the DNA tertiary structure neither in the absence nor in the
      presence of ascorbic acid, which made them incapable of reducing platinum(iv)
      compounds 2b and 2c in a buffered aqueous medium (pH 7.40) according to 1H NMR
      experiments. Remarkable topoisomerase IIalpha inhibitory activity is reported for
      platinum(iv) complexes 2b and 3a and in addition, for the last one, a moderate
      cathepsin B inhibition is reported. Cell cycle arrest (decrease in G0/G1 and G2
      phases and arrest in the S phase), induction of apoptosis and ROS generation are
      related to the antiproliferative activity of some representative octahedral
      cyclometallated platinum(iv) compounds (2b and 2c).

PMID- 29048090
TI  - Engineering a nanotubular mesoporous cobalt phosphide electrocatalyst by the
      Kirkendall effect towards highly efficient hydrogen evolution reactions.
AB  - Tailoring the size and controlling the morphology of particular nano
      architectures are considered as two promising strategies to improve the catalytic
      performance of metal nanocrystals towards hydrogen evolution reactions (HERs).
      Herein, mesoporous cobalt phosphide nanotubes (CoP-NTs) with a three-dimensional
      network structure have been obtained through a facile and efficient
      electrospinning technique combined with thermal stabilization and phosphorization
      treatments. The thermal stabilization process has been demonstrated to play a key
      role in the morphological tailoring of Co3O4 nanotubes (Co3O4-NTs). As a result,
      the CoP-NTs show one-dimensional hollow tubular architecture instead of forming a
      worm-like tubular CoP structure (W-CoP-NTs) or severely aggregated CoP powder
      (CoP-NPs) which originate from the Co3O4 nanotubes without thermal stabilization
      treatment and Co3O4 nanoparticles, respectively. Satisfyingly, under an optimized
      phosphorization degree, the CoP-NT electrode exhibits a low onset overpotential
      of 53 mV with a low Tafel slope of 50 mV dec-1 during the HER process.
      Furthermore, the CoP-NT electrode is capable of driving a large cathodic current
      density of 10 mA cm-2 at an overpotential of 152 mV, which is much lower than
      those of its contrast samples, i.e. CoP-NPs (211 mV) and W-CoP-NTs (230 mV).
      Therefore, this work provides a feasible and general strategy for constructing
      three-dimensionally organized mesoporous non-noble metal phosphide nanotubes as
      promising alternative high-performance electrocatalysts for the commercial
      platinum ones.

PMID- 29048094
TI  - Solid electrolyte interphase formation by propylene carbonate reduction for
      lithium anode.
AB  - The naturally formed solid electrolyte interphase (SEI) of lithium (Li) with
      organic electrolytes is fragile and can result in repeated exposure of fresh Li
      metal to the electrolyte during plating/stripping cycles. Building an artificial
      SEI layer is an effective way to enhance its stability and improve the
      electrochemical deposition behavior of Li. Using non-Li metal substrate to
      construct Li metal electrode is a more applicable method than using direct Li
      metal anode. In this study, the possibility of electrochemical reduction of
      propylene carbonate (PC) as an artificial SEI formation reaction for Li metal
      anode was evaluated. The results show that PC reduction can be divided into two
      stages: in the potential region higher than 0.85 V (vs. Li/Li+), the soluble free
      radical anion CH3-CH-CH2-OCO2- is formed and can be re-oxidized. In the potential
      region between 0.85 and 0.55 V (vs. Li/Li+), the insoluble reduction products
      CH3CH(-OCO2Li)CH2-OCO2Li and Li2CO3 are formed and construct the SEI film. By
      controlling the PC reduction rate with limited current, the morphology and
      construction of the SEI film could be improved, and thus the Li plating/stripping
      cycling efficiency could be enhanced. This can be considered a fundamental
      concept for high quality artificial SEI formation.

PMID- 29048095
TI  - An Asymptomatic Plaque on the Chest: A Quiz.

PMID- 29048096
TI  - Diagnostic Delay in Dermatitis Herpetiformis in a High-prevalence Area.
AB  - Dermatitis herpetiformis (DH) is an extra-intestinal manifestation of coeliac
      disease. The highest currently reported prevalence of DH is in Finland, but
      knowledge of diagnostic delay is limited. This study investigated the duration of
      rash prior to diagnosis in 446 patients with DH, analysing the results in 3
      periods of 15 years. The diagnosis was considered delayed when the duration of
      rash before diagnosis was 2 years or longer. Factors associated with delayed
      diagnosis were analysed. Within the 45 years, the median duration of rash before
      diagnosis decreased significantly, from 12.0 to 8.0 months (p?=?0.002) and the
      occurrence of a delayed diagnosis decreased from 47% to 25% (p?=?0.002). Female
      sex, the presence of villous atrophy, and a diagnosis of DH before the year 2000
      were significantly associated with delayed diagnosis. In conclusion, the present
      study showed that one-quarter of patients currently have a diagnostic delay of 2
      years or more, which is far from ideal.

PMID- 29048097
TI  - Six-month History of a Split Thumbnail: A Quiz.

PMID- 29048098
TI  - Central Obesity in Children with Psoriasis.

PMID- 29048099
TI  - Patients' Illness Perception as a Tool to Improve Individual Disease Management
      in Primary Cutaneous Lymphomas.
AB  - The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess
      illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL).
      Illness perception reflects patients' individual concepts of understanding and
      interpretation of the disease, influencing illness behaviour and health-related
      quality of life (HRQOL). This study investigated the clinical relevance of the
      relationships between illness perception, illness behaviour, and HRQOL in CTCL
      and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ
      R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific
      HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to
      illness perception, whereas illness perception was significantly associated with
      HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and
      socio-demographics. Only IPQ-R results provided practical information on
      patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and
      CBCL might be a useful instrument to improve individual disease management.

PMID- 29048101
TI  - Gallic acid inhibits the growth of calf pulmonary arterial endothelial cells
      through cell death and glutathione depletion.
AB  - Gallic acid (GA) exhibits a number of cellular effects, including apoptosis,
      which is associated with oxidative stress. The present study investigated the
      effects of GA on calf pulmonary arterial endothelial cell (CPAEC) growth and
      death, along with the levels of reactive oxygen species (ROS) and glutathione
      (GSH). GA treatment inhibited the growth of CPAECs at 24 h, and the half-maximal
      inhibitory concentration (IC50) value of GA was ~30 uM. GA treatment also induced
      cell death, which was accompanied by a loss of mitochondrial membrane potential
      (Delta?m). GA treatment in CPAECs resulted in decreased ROS levels, including O2*
      , whereas the number of GSH-depleted cells increased. Neither a pan-caspase
      inhibitor (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone) nor buthionine
      sulfoximine treatment affected GA-induced cell growth inhibition, cell death, ROS
      and GSH levels in CPAECs, whereas co-treatment with N-acetyl-cysteine (NAC)
      resulted in enhanced cell growth inhibition, cell death and Delta?m loss in these
      cells. Although NAC treatment did not significantly influence ROS levels in GA
      treated CPAECs, it significantly enhanced GSH depletion in these cells. In
      conclusion, GA inhibited the growth of CPAECs via cell death, which was
      associated with GSH depletion rather than alterations to ROS levels.

PMID- 29048100
TI  - Circadian gene hCLOCK contributes to progression of colorectal carcinoma and is
      directly regulated by tumor-suppressive microRNA-124.
AB  - An abundance of studies has demonstrated that disruption of circadian rhythms is
      one of the factors that may contribute to the initiation and development of human
      colorectal carcinomas (CRCs). Recently, microRNA-124 has been demonstrated to
      suppress tumor growth or metastasis of CRCs. However, the mechanisms of cross
      talk between microRNA-124 (miR-124) and circadian rhythms in the regulation of
      CRCs are poorly understood. The present study demonstrated that the protein
      expression levels of human circadian locomoter output cycles protein kaput
      (hCLOCK) is significantly increased, while miR-124 is attenuated in high-grade
      human CRC tissues and in the more invasive colorectal cancer cell lines SW620 and
      LOVO. It was further demonstrated that hCLOCK is a direct target of miR-124.
      Upregulation of miR-124 significantly inhibited hCLOCK expression in LOVO cells,
      and consequently inhibited its promoting effects on the proliferation and
      migration of LOVO cells. In conclusion, these data revealed that hCLOCK serves an
      enhancing role, whereas mir-124 serves a suppressive role, in human CRC.
      Attenuation of miR-124, of which hCLOCK is a direct target, leads to increased
      hCLOCK expression and disruption of circadian rhythms in CRC.

PMID- 29048102
TI  - High interpatient variability of treosulfan exposure is associated with early
      toxicity in paediatric HSCT: a prospective multicentre study.
AB  - Treosulfan-based conditioning is increasingly employed in paediatric
      haematopoietic stem cell transplantation (HSCT). Data on treosulfan
      pharmacokinetics in children are scarce, and the relationship between treosulfan
      exposure, toxicity and clinical outcome is unresolved. In this multicentre
      prospective observational study, we studied treosulfan pharmacokinetics and the
      drug's relationship with regimen-related toxicity and early clinical outcome in
      77 paediatric patients. Treosulfan dose was 30 g/m2 , administered over 3
      consecutive days in infants <1 year old (n = 12) and 42 g/m2 in children >=1 year
      old (n = 65). Mean day 1 treosulfan exposure was 1744 +/- 795 mg*h/l (10 g/m2 )
      and 1561 +/- 511 mg*h/l (14 g/m2 ), with an inter-individual variability of 56
      and 33% in the respective groups. High treosulfan exposure (>1650 mg*h/l) was
      associated with an increased risk of mucosal [Odds ratio (OR) 4.40; 95%
      confidence interval (CI) 1.19-16.28, P = 0.026] and skin toxicity (OR 4.51; 95%
      CI 1.07-18.93, P = 0.040). No correlation was found between treosulfan exposure
      and the early clinical outcome parameters: engraftment, acute graft-versus-host
      disease and donor chimerism. Our study provides the first evidence in a large
      cohort of paediatric patients of high variability in treosulfan pharmacokinetics
      and an association between treosulfan exposure and early toxicity. Ongoing
      studies will reveal whether treosulfan exposure is related to long-term disease
      specific outcome and late treatment-related toxicity.

PMID- 29048103
TI  - A four-year spontaneous remission of angioimmunoblastic T-cell lymphoma.

PMID- 29048104
TI  - Distinct clinical, laboratory and molecular features of myeloproliferative
      neoplasm patients with splanchnic vein thrombosis.

PMID- 29048105
TI  - Recurrent cardiotoxicity potentiated by the interaction of proteasome inhibitor
      and immunomodulatory therapy for the treatment of multiple myeloma.
AB  - Patients with multiple myeloma (MM) have improved treatment options, including
      immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Despite their
      efficacy, increased rates of cardiovascular (CV) complications occur in patients
      exposed to some of these therapies. While previous research has focused on
      identifying the toxicities inherent to each specific agent, the CV side effects
      may be potentiated by the combination of PIs and IMiDs plus dexamethasone. We
      present a patient with MM with recurrent cardiotoxicity only when exposed to
      combination PI and IMiD-based therapy. We also review the literature in this
      context, and propose a potential algorithm for cardiotoxicity prevention in this
      population.

PMID- 29048106
TI  - Severe granulocytic dysplasia with vacuolar rosettes in a myelodysplastic
      syndrome with low-copy KMT2A gain.

PMID- 29048107
TI  - Lenalidomide and dexamethasone in patients with POEMS syndrome: results of a
      prospective, open-label trial.
AB  - Given its anti-angiogenic activity, lenalidomide may have a role in the treatment
      of POEMS (Peripheral neuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma
      cell disorder and Skin changes) syndrome. This prospective, open-label, pilot
      study evaluated the combination of lenalidomide + dexamethasone (RD) in 18 POEMS
      syndrome patients (13 pre-treated, 5 newly-diagnosed but ineligible for high-dose
      therapy). Treatment consisted of six cycles of lenalidomide (25 mg/day for 21
      days followed by 7 days rest) plus dexamethasone (40 mg/once a week). Patients
      responding after six cycles continued treatment until progression or unbearable
      toxicity. The primary endpoint was the proportion of patients with either
      neurological or clinical improvement. The RD combination was considered as
      deserving further evaluation if 9 of the first 15 patients responded. Ten
      responses were observed among the first 15 enrolled patients, meeting the primary
      endpoint. Fifteen of 18 patients (83%) completed six RD cycles: 13 (72%) patients
      responded and nine had both clinical and neurological improvement. Among the 15
      patients who completed the six RD cycles, four were still on treatment after a 25
      month follow-up. At 39 months of follow-up, all patients were alive with a 3-year
      progression-free survival of 59%. No patient discontinued RD for toxicity.
      Overall, the RD regimen showed a high incidence of prolonged symptoms improvement
      and was well tolerated in most POEMS patients.

PMID- 29048108
TI  - Renin-angiotensin system blockade promotes a cardio-renal protection in
      albuminuric homozygous sickle cell patients.
AB  - The management of sickle cell nephropathy (SCN) at an early stage is an important
      issue to prevent renal and cardiovascular morbidity and mortality. This study
      aimed to evaluate in this population, whether angiotensin converting enzyme
      inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN
      cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10
      mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured
      glomerular filtration rate (mGFR) together with haematological and cardiovascular
      parameters. A 1-month washout was also performed in order to differentiate short-
      and long-term ACEIs effects. A decrease in ACR baseline value (>30%) was detected
      in 62% of cases (mean ACR: 46.4 +/- 7.6 and 26.4 +/- 3.9 mg/mmol at baseline and
      6 months respectively; P = 0.002), whereas mGFR values were unchanged. ACR
      decrease was detected at 1 month following ACEI initiation (32.9 +/- 6.9, P =
      0.02) with a persistent trend after withdrawal (P = 0.08). ACEIs also decreased
      diastolic blood pressure (P = 0.007), pulse wave velocity (P = 0.01), tricuspid
      regurgitation velocity (TRV; P = 0.04), asymmetric dimethyl arginine (ADMA: P =
      0.001) and haemoglobin (P = 0.01) while conventional haemolytic biomarkers were
      unchanged. Our data suggest that ACEIs are safe and effective at decreasing
      albuminuria in sickle cell patients with a beneficial effect on specific
      mortality risk factors, such as TRV and asymmetric dimethyl arginine.

PMID- 29048110
TI  - Morphometric and morphologic parameters of the heart in healthy Alouatta guariba
      clamitans (Cabrera, 1940).
AB  - BACKGROUND: This study aimed at assessing the heart function of one neotropical
      primate (Alouatta guariba clamitans) kept in captivity using radiography,
      electrocardiogram (ECG) and Doppler echocardiography. METHODS: Ten adult healthy
      howler monkeys (A. g. clamitans) were evaluated under general anaesthesia.
      Vertebral Heart Scores (VHS) were obtained from radiographic studies. Ejection
      fraction, shortening fraction of left ventricle, left atrial/aortic root ratio,
      ascending aortic diameter, peak velocity of pulmonary, mitral, tricuspid and
      aortic blood flow and other values were measured by Doppler echocardiography.
      Heart rate, mean electrical axis of QRS complex, P, Q, R, S, T amplitude, P, PR
      interval, QRS, QT interval duration and ST segment unbalancing were measured by
      ECG. RESULTS AND CONCLUSIONS: Exam techniques were akin the ones used in humans.
      Doppler echocardiographic, radiographic, electrocardiographic and clinical
      parameters for howler monkey were described and correlated. The results have
      shown profiles of cardiovascular function and structure of A. g. clamitans.

PMID- 29048109
TI  - Evaluation of a disease risk index for adult patients undergoing umbilical cord
      blood transplantation for haematological malignancies.
AB  - A disease risk index (DRI) has been defined for stratifying heterogeneous cohorts
      of patients undergoing allogeneic haematopoietic stem cell transplantation
      (HSCT). This index defines 4 distinct groups with different outcomes, dividing
      patients by disease type and status and considering cytogenetics for acute
      myeloid leukaemia and myelodysplastic syndromes (MDS). Recently, the DRI has been
      refined to include rare diseases and improve MDS stratification by blast
      percentage and response to prior therapy. Previous reports on DRI include only a
      small number of UCBT recipients. The current study aims to determine the
      applicability of the DRI for patients undergoing unrelated cord blood
      transplantation (UCBT). We retrospectively analysed 2530 adults receiving UCBT
      between 2004 and 2014. Diagnosis was acute leukaemia (AL) in 66% of the cases.
      Overall survival (OS) at 2 years was 56 +/- 3% for patients with low DRI (n =
      352), 46 +/- 1% for intermediate DRI (n = 1403), 28 +/- 2% for high (n = 489) and
      20 +/- 4% for very high DRI (n = 109) (P < 0.001). In the multivariate model, DRI
      remained an independent risk factor for OS. Similar findings were observed for
      PFS and DRI. Our results show the applicability of DRI for stratifying UCBT
      recipients and confirm the prognostic value of this simple and robust tool in
      this setting.

PMID- 29048111
TI  - Cerebrospinal fluid leak after bone marrow biopsy.

PMID- 29048112
TI  - How we diagnose and treat systemic mastocytosis in adults.
AB  - Rapid advances in the understanding of the molecular biology, data from
      translational and clinical trials, and retrospective analyses has influenced the
      diagnosis and treatment of systemic mastocytosis (SM). Many options have existed
      for the symptomatic management of SM patients, but recent evolution in regards to
      the molecular underpinnings of this disease and our ability to distinguish clonal
      mastocytosis from mast cell activation syndrome has changed our treatment
      paradigm and opened new opportunities for understanding genetic risk,
      transformation to mast cell leukaemia, and treatment choices. Key to this change
      has been the discovery of the KIT mutation and the use of next generation
      sequencing to evaluate for co-existing molecular mutations that may define the
      disease course. Careful diagnosis, judicious symptom management and close
      surveillance of those who may have yet undiagnosed disease is paramount in
      providing optimal management. In this article, we review the diagnosis and
      provide a paradigm for the management of SM patients.

PMID- 29048114
TI  - Relapsing polychondritis as a presenting feature of acute myeloid leukaemia.

PMID- 29048116
TI  - The interaction of phalloidin, some of its derivatives, and of other cyclic
      peptides with muscle actin as studied by viscosimetry.

PMID- 29048117
TI  - Elevations in serum glycoprotein:N-acetylneuraminic acid transferases in rats
      bearing mammary tumors.

PMID- 29048113
TI  - Salicylic acid-dependent immunity contributes to resistance against Rhizoctonia
      solani, a necrotrophic fungal agent of sheath blight, in rice and Brachypodium
      distachyon.
AB  - Rhizoctonia solani is a soil-borne fungus causing sheath blight. In consistent
      with its necrotrophic life style, no rice cultivars fully resistant to R. solani
      are known, and agrochemical plant defense activators used for rice blast, which
      upregulate a phytohormonal salicylic acid (SA)-dependent pathway, are ineffective
      towards this pathogen. As a result of the unavailability of genetics, the
      infection process of R. solani remains unclear. We used the model
      monocotyledonous plants Brachypodium distachyon and rice, and evaluated the
      effects of phytohormone-induced resistance to R. solani by pharmacological,
      genetic and microscopic approaches to understand fungal pathogenicity.
      Pretreatment with SA, but not with plant defense activators used in agriculture,
      can unexpectedly induce sheath blight resistance in plants. SA treatment inhibits
      the advancement of R. solani to the point in the infection process in which
      fungal biomass shows remarkable expansion and specific infection machinery is
      developed. The involvement of SA in R. solani resistance is demonstrated by SA
      deficient NahG transgenic rice and the sheath blight-resistant B. distachyon
      accessions, Bd3-1 and Gaz-4, which activate SA-dependent signaling on
      inoculation. Our findings suggest a hemi-biotrophic nature of R. solani, which
      can be targeted by SA-dependent plant immunity. Furthermore, B. distachyon
      provides a genetic resource that can confer disease resistance against R. solani
      to plants.

PMID- 29048118
TI  - A pteridine adsorbent for affinity chromatography.

PMID- 29048119
TI  - Immunopurification of phospholipase C (alpha-toxin) from Clostridium perfringens.

PMID- 29048121
TI  - Formation and decay of peroxy radicals of some pyrimidine derivatives in water.

PMID- 29048120
TI  - Inhibition of pyruvate and beta-hydroxy buty rate oxidation in rat brain
      mitochondria by phenylpyruvate and alpha-ketoisocaproate.

PMID- 29048122
TI  - Chemical modification of cholera toxin for characterization of antigenic receptor
      binding and toxic sites.

PMID- 29048123
TI  - A precursor of the neck appendage protein of B. subtilis phage Phi 29.

PMID- 29048124
TI  - The binding of microsomal hydroxylation substrates to cytochrome P-450Rh and its
      effect on the nitrogen fixation by lupin bacteroids.

PMID- 29048125
TI  - TCL1A interacts with TP63 and enhances the survival of Raji Burkitt lymphoma cell
      line.

PMID- 29048126
TI  - Elimination of different leukaemia subtypes using novel CD89-specific human
      cytolytic fusion proteins.

PMID- 29048127
TI  - A highly purified form of staphylococcal protein A alleviates murine immune
      thrombocytopenia (ITP).

PMID- 29048128
TI  - How I manage relapse of chronic myeloid leukaemia after stopping tyrosine kinase
      inhibitor therapy.
AB  - During the last 10 years, clinical trials formally demonstrated that about 50% of
      patients with chronic phase (CP) chronic myeloid leukaemia (CML) who achieve and
      maintain deep molecular responses for a prolonged period of time during treatment
      with imatinib or new generation tyrosine kinase inhibitors (TKIs) may
      successfully stop their anti-leukaemic therapy. Based on the accumulated
      knowledge from abundant clinical trial experience, TKI discontinuation is
      becoming an important goal to achieve and is about to enter clinical practice.
      This review focuses on relapse definition, laboratory tests to identify relapse
      and relapse management after TKI discontinuation.

PMID- 29048131
TI  - Sickness absence following breast cancer surgery: a two-year follow-up cohort
      study.
AB  - RATIONALE AND AIM: Most women of working ages with limited breast cancer (BC)
      have returned to work within the first year after diagnosis. However, little is
      known about what is happening during this year regarding sickness absence and
      return to work. Also, the knowledge is very limited about the occurrence of part
      time sickness absence after BC diagnosis. Therefore, the aim of this study was to
      describe occurrence, extent and length of SA during a two-year follow-up after BC
      surgery and to analyse the association between being SA and type of cancer
      treatment. METHODS: In this prospective cohort study, 497 women responded to
      questionnaires about different aspects of sickness absence at six occasions
      during two years after primary BC surgery (at baseline and after 4, 8, 12, 18 and
      24 months). Treatment information was obtained from the National breast cancer
      register. Multinomial logistic regression was used to calculate odds ratios (OR)
      for likelihood of being sickness absent more than once. RESULTS: Two-thirds of
      the women were sickness absent at baseline; this proportion decreased, especially
      during the first eight months. At 24 months, 13% were sickness absent. Of all
      women, 27% never reported sickness absence and 14% were sickness absent at most
      of the six survey times. At eight months, many had shifted from full- to part
      time sickness absence. Women with chemotherapy and/or advanced BC surgery had
      higher ORs for being sickness absent at most of the follow-ups. CONCLUSIONS: Most
      women returned to work within the first eight months after BC surgery and of
      those sickness absent after that, most had been part-time sickness absent. Thus,
      it is important to differentiate between part- and full-time sickness absence in
      future studies. Special attention should be paid to the impact of chemotherapy
      and type of surgery on the likelihood of being sickness absent.

PMID- 29048129
TI  - Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo
      activity against multiple myeloma.
AB  - Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation
      of plasma cells in the bone marrow, remains incurable despite the use of novel
      and conventional therapies. In this study, we demonstrated MM cell cytotoxicity
      triggered by realgar (REA; As4 S4 ) nanoparticles (NREA) versus Arsenic trioxide
      (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo
      anti-MM activity, resulting in significantly decreased tumour burden. The anti-MM
      activity of NREA and ATO is associated with apoptosis, evidenced by DNA
      fragmentation, depletion of mitochondrial membrane potential, cleavage of
      caspases and anti-apoptotic proteins. NREA induced G2 /M cell cycle arrest and
      modulation of cyclin B1, p53 (TP53), p21 (CDKN1A), Puma (BBC3) and Wee-1 (WEE1).
      Moreover, NREA induced modulation of key regulatory molecules in MM pathogenesis
      including JNK activation, c-Myc (MYC), BRD4, and histones. Importantly, NREA, but
      not ATO, significantly depleted the proportion and clonogenicity of the MM stem
      like side population, even in the context of the bone marrow stromal cells.
      Finally, our study showed that both NREA and ATO triggered synergistic anti-MM
      activity when combined with lenalidomide or melphalan. Taken together, the anti
      MM activity of NREA was more potent compared to ATO, providing the preclinical
      framework for clinical trials to improve patient outcome in MM.

PMID- 29048130
TI  - Beneficial effect of exogenous platelet factor 4 for detecting pathogenic heparin
      induced thrombocytopenia antibodies.
AB  - The laboratory diagnosis of heparin-induced thrombocytopenia (HIT) is based on an
      enzyme immunoassay combined with a functional test, and serotonin release assay
      (SRA) is the gold standard for detecting activating HIT antibodies. However, a
      recent atypical history of HIT prompted us to evaluate whether addition of
      platelet factor 4 (PF4) during SRA could improve its ability to detect pathogenic
      HIT antibodies. Using 5B9, a monoclonal antibody to PF4/H with a human Fc
      fragment, we first defined the optimal PF4 concentration for detecting low
      amounts of platelet-activating IgG with SRA. Plasma samples from 50 patients with
      suspected HIT were then studied, and SRA was positive in 17 cases (Group SRApos
      ), with relatively high levels of PF4-specific IgG (median optical density =
      2.66). SRA was also systematically performed after adding 10 MUg/ml of PF4 in the
      reaction mixture, and significant serotonin release was measured with samples
      from 9 additional patients (Group PF4-SRApos ). Importantly, levels of PF4
      specific IgG were similar in these samples and those from the 24 persistently SRA
      negative patients. Moreover, the pre-test probability of HIT was
      intermediate/high in all 'SRApos ' or 'SRA-PF4pos ' patients. In conclusion,
      addition of exogenous PF4 might improve the detection of pathogenic HIT
      antibodies by SRA.

PMID- 29048132
TI  - Comparison of the Efficiency of Ultrasound-Guided Injections of the Rhomboid
      Major and Trapezius Muscles in Myofascial Pain Syndrome: A Prospective Randomized
      Controlled Double-blind Study.
AB  - OBJECTIVES: We aimed to investigate the effect of ultrasound (US)-guided
      injections of the rhomboid major (deep) and trapezius (superficial) muscles on
      pain, disability, and quality of life in patients with myofascial pain syndrome.
      METHODS: In this prospective randomized controlled double-blind study, 65
      patients with a diagnosis of myofascial pain syndrome were randomized into 2
      groups. In group 1 (n = 33), US-guided rhomboid major muscle injection was
      performed, and in group 2 (n = 32), US-guided trapezius muscle injection was
      performed. The patients were assessed by a visual analog scale for pain, the
      Pressure Pain Threshold, the Neck Pain and Disability Scale, and Short Form 12.
      Data were obtained before treatment (week 0), the second week after treatment,
      and the fourth week after treatment. RESULTS: In both groups, significant
      improvements were observed for all parameters at both weeks 2 and 4 compared to
      pretreatment values (P < .05). A comparison of the groups showed significantly
      superior results in group 1 for all parameters at week 2 (P < .05) and for all
      parameters but the Physical Component Scale of Short Form 12 at week 4 (P < .05).
      CONCLUSIONS: We think that US-guided deep injection of the rhomboid major muscle
      was more effective than superficial injection of the trapezius muscle for pain,
      disability, and quality of life in patients with myofascial pain syndrome.

PMID- 29048133
TI  - Vasa Previa: Prenatal Diagnosis and Outcomes: Thirty-five Cases From a Single
      Maternal-Fetal Medicine Practice.
AB  - OBJECTIVES: To assess the accuracy and effectiveness of routine screening for
      vasa previa, to describe our experience, and to assess factors that contribute to
      missed cases of vasa previa. METHODS: A retrospective descriptive study of all
      cases of vasa previa from a single maternal-fetal medicine service between 2009
      and 2017 was performed. Ultrasound findings and obstetric and neonatal outcomes
      were reviewed and analyzed. RESULTS: Thirty-five cases of vasa previa were
      identified. Most cases (33 of 35 [94.3%]) were diagnosed antenatally. All 33
      cases that followed our screening protocol were diagnosed antenatally and had
      favorable outcomes. Two cases that did not follow our protocol were not diagnosed
      antenatally and were delivered emergently. The mean gestational age +/- SD at
      delivery of antenatally diagnosed cases was 34.9 +/- 1.69 weeks. All neonates
      survived. CONCLUSIONS: Routine ultrasound screening for vasa previa using
      American Institute of Ultrasound in Medicine criteria will almost universally
      lead to good outcomes and prevent perinatal mortality.

PMID- 29048134
TI  - Necrobiotic xanthogranuloma treated with lenalidomide.

PMID- 29048136
TI  - Controllable Hierarchical Surface Patterns of Supramolecular Hydrogels:
      Harnessing Buckling Instability by Confinement.
AB  - Patterned surfaces of responsive polymers find applications in diverse fields.
      However, it is still a great challenge to fabricate hierarchical patterns with
      long-range orders. Herein controllable hierarchical surface patterns that can be
      fabricated by combining nanoembossing techniques with the surface instability of
      supramolecular hydrogels are presented. Nanoembossed nanostripe arrays of
      polyethylene glycol (PEG)-based polyurethane-urea supramolecular hydrogels are
      fabricated and exposed to water, whereby the lateral expansion of nanostripes is
      confined and leads to the formation of folded in-plane or out-of-plane patterns
      depending on the aspect ratios. The direction of folds is perpendicular to the
      nanostripes. Both the amplitude and the wavelength of out-of-plane folds are
      proportional to the thickness of nanostripes. Therefore, hierarchical structures,
      in which one periodicity is defined by the nanoembossing processes and the other
      is determined by surface buckling, can be quickly fabricated in supramolecular
      hydrogel thin films.

PMID- 29048135
TI  - Oligonucleotides with Cationic Backbone and Their Hybridization with DNA:
      Interplay of Base Pairing and Electrostatic Attraction.
AB  - Non-natural oligonucleotides represent important (bio)chemical tools and
      potential therapeutic agents. Backbone modifications altering hybridization
      properties and biostability can provide useful analogues. Here, we employ an
      artificial nucleosyl amino acid (NAA) motif for the synthesis of oligonucleotides
      containing a backbone decorated with primary amines. An oligo-T sequence of this
      cationic DNA analogue shows significantly increased affinity for complementary
      DNA. Notably, hybridization with DNA is still governed by Watson-Crick base
      pairing. However, single base pair mismatches are tolerated and some degree of
      sequence-independent interactions between the cationic NAA backbone and fully
      mismatched DNA are observed. These findings demonstrate that a high density of
      positive charges directly connected to the oligonucleotide backbone can affect
      Watson-Crick base pairing. This provides a paradigm for the design of therapeutic
      oligonucleotides with altered backbone charge patterns.

PMID- 29048138
TI  - Ventilation in Preterm Infants and Lung Function at 8 Years.

PMID- 29048137
TI  - The impact of passive smoking on the risk of colorectal neoplasia in never,
      former, and current smokers.
AB  - BACKGROUND AND AIM: Active smoking is well known to be a risk factor for
      colorectal neoplasia (CRN). However, it remains unclear whether passive smoking
      is also related to the risk of CRN. This study investigated the effect of passive
      smoking on the risk of CRN in never, former, and current smokers. METHODS: A
      cross-sectional study was performed on asymptomatic examinees who underwent
      colonoscopy as part of a health check-up. RESULTS: Of 136 707 participants, 33
      052 (24.2%) were never passive smokers, and 103 655 (75.8%) were ever passive
      smokers. The mean age of the study population was 41.0 years. The proportion of
      never, former, and current smokers was 56.9%, 21.4%, and 24.8%, respectively, and
      the proportion of overall CRN and advanced CRN (ACRN) was 15.4% and 1.7%,
      respectively. Ever passive smoke exposure was associated with an increased risk
      of overall CRN in never smokers (adjusted odds ratio [AOR] 1.08; 95% confidence
      interval [CI] 1.02-1.13) and former smokers (AOR 1.08; 95% CI 1.00-1.17) but not
      in current smokers (AOR 1.02; 95% CI 0.94-1.11). Additionally, it significantly
      increased the risk of ACRN among never smokers (AOR 1.17; 95% CI 1.01-1.35) and
      tended to increase the risk of ACRN among former smokers (AOR 1.26; 95% CI 0.99
      1.61). Moreover, the risk of CRN increased with increasing frequency and duration
      of passive smoking in never and former smokers. CONCLUSIONS: Passive smoking was
      an independent risk factor for CRN in never and former smokers. Never and former
      smokers who are highly exposed to passive smoke as well as current smokers should
      be given priority for colonoscopy.

PMID- 29048139
TI  - The relevance of existing health communication models in the email age:
      Anintegrative literature review.
AB  - Email communication is being integrated relatively slowly into doctor-patient
      communication.Patients have expressed enthusiasm for the medium, while doctors
      are generally morereluctant. As existing health communication models have
      characteristically assumed the co-presenceof doctor and patient and primarily
      reflect medical practitioners' perspectives, theirsuitability in relation to
      email communication and patients' perspectives warrants further
      investigation.Following a two-step process and using the methodology of the
      integrative literaturereview, 29 articles from 2004-2014 are analysed with the
      aim of investigating the advantagesand disadvantages of the medium of email from
      the patient's perspective. The findings arecompared to the health communication
      models of biomedicine, patient-centeredness, patienteducation and patient
      empowerment to investigate these models' relevance for doctor-patientemail
      communication. Results show that patients identify numerous advantages with email
      communication, including improved convenienceand access, more detailed
      informational exchanges, greater reflection opportunities, freedomfrom the
      medical gaze and the potential to level out power imbalances, as well as a
      numberof primarily medium-related disadvantages. The findings indicate that email
      can counteractsome of the communicative problems associatedwith biomedicine and
      suggest the ongoing relevance of aspects of the models of patient
      empowerment,patient-centeredness and patient education for email communication.

PMID- 29048140
TI  - Ventilation in Preterm Infants and Lung Function at 8 Years.

PMID- 29048141
TI  - Conceptualizing 'role' in patient-engaging e-health: A cross-disciplinary review
      ofthe literature.
AB  - Patient-engaging e-health is promoted as a means toimprove care and change the
      social order of healthcare- most notably the roles of patients and
      healthcareprofessionals. Nevertheless, while researchersacross various fields
      expect and praise such changes,these social aspects are rarely addressed
      rigorously inthe literature on the effects of e-health.In this paper we review
      the scientific literatureon patient-engaging e-health, with the purpose
      ofarticulating the different ways in which role is conceptualizedin the various
      strands of literature andwhat explicit and implicit assumptions such
      conceptualizationsentail. We identify three conceptualizationsof the concept of
      role and exemplify the findingsproposed by studies that apply each of these.
      Weargue that the identified conceptual differences haveimplications for what is
      found to be at stake whenusing e-health to further the involvement of patientsin
      their own care, and that a more rigorous and reflectiveapproach to the use of
      concepts with rich intellectualhistories, such as that of role, will improveboth
      empirical research in e-health and discussionsof implications for practice.

PMID- 29048142
TI  - Amyotrophic Lateral Sclerosis

PMID- 29048143
TI  - Participatory research design in mobile health: Tablet devices for diabetes self
      management.
AB  - Type 2 diabetes is a prevalent, chronic disease, whichplaces significant burden
      on societies and individuals.This article reports the participatory
      researchdesign of an exploratory study that introduces mobiletablet devices in
      the self-management of type 2diabetes in a primary healthcare setting.
      Strategiesfrom democratic dialogic theory were used in the designof the research
      to steer the participatory engagementbetween researchers and healthcare
      practitioners.The outcome of this phase of the research was theissue of six
      'invitations' to 28 people with diabetesto frame their use of a mobile tablet
      device in managingtheir health. Those invitations were clusteredin two themes,
      Empowered and Compelled, representingtypical patient attitudes and behaviours.
      Thework reported here sets the stage for a longitudinaland socially complex study
      that encompasses a newand comprehensive General Practitioner (GP) SuperClinic
      with an array of health and administrativestaff, patients with a chronic health
      condition requiringcontinual self-management, a wide continuum ofdigital literacy
      capability in all participants and anever-increasing digital society. It reports
      a novel researchdesign methodology that merges democraticdialogic theory and
      participatory design, resulting ina grounded and agreed approach to a mobile
      healthintervention.

PMID- 29048144
TI  - Involving patients, families and medical staff in the evaluation of 3D
      printingmodels of congenital heart disease.
AB  - OBJECTIVE: To develop a participatory approach inthe evaluation of 3D printed
      patient-specific modelsof congenital heart disease (CHD) with
      differentstakeholders who would potentially benefit from thetechnology (patients,
      parents, clinicians and nurses). METHODS: Workshops, focus groups and
      teachingsessions were organised, targeting different stakeholders.Sessions
      involved displaying and discussingdifferent 3D models of CHD. Model
      evaluationinvolved response counts from questionnaires andthematic analysis of
      audio-recorded discussions andwritten feedback. RESULTS: Stakeholders' responses
      indicated thescope and potential for clinical translation of 3Dmodels. As
      tangible, three-dimensional artefacts,these can have a role in communicative
      processes.Their patient-specific quality is also important in relationto
      individual characteristics of CHD. Patientsindicated that 3D models can help them
      visualise'what's going on inside'. Parents agreed that modelscan spark curiosity
      in young people. Clinicians indicatedthat teaching might be the most relevant
      application.Nurses agreed that 3D models improved theirlearning experience during
      a CHD course. CONCLUSION: Engagement of different stakeholdersto evaluate 3D
      printing technology for CHD identifiedthe potential of the models for improving
      patient-doctor communication, patient empowermentand training. PRACTICE
      IMPLICATIONS: A participatory approachcould benefit the clinical evaluation and
      translationof 3D printing technology.

PMID- 29048145
TI  - 'Shift' 'n 'control': The computer as a third interactant in Spanish
      languagemedical consultations.
AB  - The purpose of this paper is to examine the role of thecomputer in medical
      consultations in which English-Spanish-bilingual medical providers interact
      withSpanish-monolingual patients. Following previousstudies that have revealed
      that the presence of thecomputer in consultations detracts from direct provider
      patient communication, we pay specific attentionto how the use of the computer in
      Spanish-languagemedical consultations can complement oradversely affect the co
      construction of the patient'shealth narrative. The data for the present study
      consistof 36 Spanish-language medical consultationsin Southern California.
      Applying a conversationanalytical approach to the health narratives in thecorpus,
      we argue that the computer is essentially athird interactant to which medical
      providers orientthrough lowered volume, minimal responses, bureaucraticside talk,
      and, most importantly, code-switchingto English - all of which strip the
      patientsof control over the co-construction of their healthnarrative with their
      medical provider. Because thepatient does not have access to the
      computationaltask and the language, we posit that this exacerbatesthe already
      existing adverse effects that the computerhas on provider-patient interaction.

PMID- 29048146
TI  - Exploring web-mediated communication: A genre-based linguistic study for
      newpatterns of doctor-patient interaction in online environment.
AB  - This paper questions the nature of the communicativeevent that takes place in
      online contexts betweendoctors and web-users, showing computer-mediatedlinguistic
      norms and discussing the nature of theparticipants' roles. Based on an analysis
      of 1005posts occurring between doctors and the users ofhealth service websites, I
      analyse how doctor-patientcommunication is affected by the medium and howhealth
      professionals overcome issues concerning thevirtual medical visit. Results
      suggest that (a) onlinemedical answers offer a different service from
      thatexpected by users, as doctors cannot always fulfillpatient requests, and (b)
      net consultations use aspectsof traditional doctor-patient exchange andyet
      present a language and a style that are affectedby the computer-mediated
      environment. Additionally,it seems that this new form leads to a differentmodel
      of doctor-patient relationship. The findingsare intended to provide new insights
      into web-baseddiscourse in doctor-patient communication and todemonstrate the
      emergence of a new style in medicalcommunication.

PMID- 29048147
TI  - Practical videoconference training: Experience from a Norwegian resource
      centrefor rare disorders.
AB  - A pilot programme was developed for trainingprofessionals to communicate in
      counsellingsituations via videoconferencing, with participantsfrom Norwegian
      resource centres for raredisorders. The programme was conducted atthree
      videoconferencing studios, and entailedthree sessions involving role play,
      feedback,reflection, and discussion. After each session,participants received a
      short web-based questionnaire.The programme was generally perceivedas realistic,
      with 95% of participantsconsidering it to be a suitable training methodand 94%
      reporting greater awareness of howto engage successfully in dialogue during
      videoconferencing.Those who experienced technicaldifficulties reported
      significantly lowersatisfaction with the role play, feedback, anddiscussion
      segments. Experiences conveyed inthe feedback and reflection segments are
      described,demonstrating the importance of anappropriate technical infrastructure
      and givinguseful insights into how videoconferencesshould be performed. The
      programme could bereplicated and developed further and offered toprofessionals
      who give counselling services via videoconferences.

PMID- 29048148
TI  - 'Am I anorexic?' Weight, eating and discourses of the body in online
      adolescenthealth communication.
AB  - This article explores the communicative choices ofadolescents seeking advice from
      an internet-basedhealth forum run by medical professionals. Techniquesfrom the
      disciplines of sociolinguistics andcorpus linguistics are integrated to examine
      thestrategies used in adolescents' health questions. Wefocus on the emergent
      theme of Weight and Eating,a concern which features prominently in
      adolescents'requests to medical practitioners. The majority ofadvice requests are
      authored by adolescent girls,with queries peaking at age 12. A combined
      quantitativeand qualitative analysis provides detailedinsights into adolescents'
      communicative strategies.Examinations of question types, register anda discourse
      based analysis draw attention to dominantdiscourses of the body, including a
      'discourseof slenderness' and a 'discourse of normality', whichexercise negative
      influences on adolescents' dietarybehaviours. The findings are of applied
      linguistic relevanceto health practitioners and educators, as theyprovide them
      with access to adolescents' health queriesin their own language.

PMID- 29048149
TI  - Management of inflammatory bowel disease flares in the emergency department
AB  - Because of the chronic relapsing nature of inflammatory bowel disease (IBD),
      emergency clinicians frequently manage patients with acute flares and
      complications. IBD patients present with an often-broad range of nonspecific
      signs and symptoms, and it is essential to differentiate a mild flare from a life
      threatening intra-abdominal process. Recognizing extraintestinal manifestations
      and the presence of infection are critical. This issue reviews the literature on
      management of IBD flares in the emergency department, including laboratory
      testing, imaging, and identification of surgical emergencies, emphasizing the
      importance of coordination of care with specialists on treatment plans and
      offering patients resources for ongoing support.

PMID- 29048150
TI  - Carboxymethylated Dextran-Modified N-Heterocyclic Carbene Self-Assembled
      Monolayers on Gold for Use in Surface Plasmon Resonance Biosensing.
AB  - Surface chemistry is a key enabler for various biosensing applications.
      Biosensors based on surface plasmon resonance routinely employ thiol-based
      chemistry for the linker layer between gold-coated support surfaces and
      functional biosensor surfaces. However, there is a growing awareness that such
      sensor surfaces are prone to oxidation/degradation problems in the presence of
      oxygen, and previous efforts to improve the stability have shown limited
      advancements. As an alternative, recent studies employing N-heterocyclic carbene
      (NHC) self-assembled monolayers (SAMs) deposited on gold have shown significant
      promise in this area. Here, we describe a sensor surface employing an NHC SAM to
      couple a modified carboxymethylated dextran onto a gold surface. Such a dextran
      matrix is also used for affinity chromatography, and it is the most commonly
      employed matrix for commercial biosensor surfaces today. The performance
      reliability of the dextran-modified NHC chip to act as an alternative biosensing
      platform is compared with that of a thiol-based commercial chip in the proof-of
      concept tests. The resultant NHC sensor surface shows a higher thermal stability
      compared to thiol analogues. Moreover, the plasma protein/drug and
      antibody/antigen interactions were validated on the NHC-based dextran chip and
      showed similar performance as compared to the thiol-based commercial chip.
      Ultimately, this study shows the strong potential applicability of chemical
      modifications to gold surfaces using NHC ligands for biosensing applications.

PMID- 29048152
TI  - A New Chemometric Approach for Automatic Identification of Microplastics from
      Environmental Compartments Based on FT-IR Spectroscopy.
AB  - One key step studying interactions of microplastics with our ecological system is
      to identify plastics within environmental samples. Aging processes and surface
      contamination especially with biofilms impede this characterization. A complex
      and time-consuming cleaning procedure is a common solution for this problem.
      However, it implies an artificial change of sample composition with a risk of
      losing important information or even damaging microplastic particles. In the
      present work, we introduce a new chemometric approach to identify heavily
      weathered and contaminated microplastics without any cleaning. The main idea of
      this concept is based on an automated curve fitting of most relevant vibrational
      bands to calculate a highly characteristic fingerprint that contains all
      vibrational band area ratios. This new data set will be used to estimate the
      similarity of samples and reference standards for identification. A total of 300
      individual naturally weathered plastic particles were measured with Fourier
      transformation infrared spectroscopy in attenuated total reflection mode (FT-IR
      ATR) and identified successfully with the new method. To that end, all samples
      were compared with a selection of common reference plastics and bio polymers. As
      it turns out, the accuracy of identification rises significantly from 76% by
      means of conventional library searching algorithms to 96% by identifying
      microplastics with our new method. Therefore, the new approach can be a useful
      tool to compare and describe similarities of FT-IR spectra of microplastics,
      which may improve further research studies on this topic.

PMID- 29048151
TI  - Fabrication of Plasmonically Active Substrates Using Engineered Silver
      Nanostructures for SERS Applications.
AB  - Demanding applications in sensing, metasurfaces, catalysis, and biotechnology
      require fabrication of plasmonically active substrates. Herein, we demonstrate a
      bottom-up, versatile, and scalable approach that relies on direct growth of
      silver nanostructures from seed particles that were immobilized on polymer brush
      grafted substrates. Our approach is based on (i) the uniform and tunable assembly
      of citrate-stabilized gold nanoparticles on poly(ethylene glycol) brushes to
      serve as seeds and (ii) the use of hydroquinone as a reducing agent, which is
      extremely selective to the presence of seed particles, confining the growth of
      silver nanostructures on the surface of the substrate. The diameter of the seed
      particles, concentration, as well as ratio of reactants and duration of the
      growth process are investigated for large-area growth of silver nanostructures
      with high surface coverage and plasmonic activity. The resulting silver
      nanostructures exhibit high levels of surface-enhanced Raman scattering activity
      at two different laser lines and allow detection of molecules at concentrations
      as low as 10 pM. The plasmonic properties of the silver nanostructures are
      further studied using ultrafast pump-probe spectroscopy. Spatially defined silver
      nanostructures are fabricated through the seed particles that are patterned via
      soft lithography, showing the capabilities of the presented approach in device
      applications.

PMID- 29048153
TI  - Controlled Photoerasable Fluorescent Behaviors with Dithienylethene-Based
      Molecular Turnstile.
AB  - The precise control of molecular interaction and motion is a powerful strategy in
      the creation and development of intelligent materials. We demonstrate here a
      simple concept and approach to integrate intramolecular photochromic property
      with intermolecular aggregation-induced emission behaviors, with the aim to
      construct a new type of photoswitchable luminescent materials. This strategy is
      realized by the dithienylethene-bridged bispyridinium salt as photochromic
      molecular turnstile, and their subsequent fabrication into optically functional
      materials is reported. By restricting the rotation of central chemical bonds, the
      obtained molecular turnstile not only exhibits photocontrolled fluorescence
      emission through solvent exchange but is also capable of transforming into
      photowritable and photoerasable films in polymeric matrix with good
      recyclability. This functional molecular turnstile provides convenient routes to
      construct photochromic nanomaterials with controlled photophysical behaviors.

PMID- 29048154
TI  - Hexanuclear and Trinuclear Metal Complexes of a Giant Octadecaaza Macrocycle.
AB  - A large macrocyclic ligand containing six pyridine fragments and six
      diaminocyclopentane fragments is able to form hexanuclear Zn(II) and Ni(II)
      complexes as well as a trinuclear Zn(II) complex. X-ray crystal structures of
      these complexes indicate quite different ligand conformations. In the hexanuclear
      Zn(II) derivative with chloride counteranions metal ions have a distorted
      trigonal-bipyramidal geometry and occupy loop sections formed by the highly
      folded macrocycle, which adopts a globular shape. In the hexanuclear Ni(II)
      derivative with nitrate counteranions metal ions exhibit a distorted-octahedral
      geometry and the ligand conformation is much more open, while in the trinuclear
      Zn(II) complex the macrocycle wraps around the octahedral metal ions. The last
      highly entangled conformation of the trinuclear complex is also present in
      solution, as confirmed by the NOESY spectra. The NMR data indicate that the
      hexanuclear Zn(II) complex partially dissociates in water solutions to form the
      trinuclear complex, while the 1H NMR titration of the free macrocycle with
      zinc(II) chloride indicates that the formation of a trinuclear complex
      corresponds to cooperative binding of metal ions.

PMID- 29048155
TI  - Wavelengths and Lifetimes of Paper Autofluorescence: A Simple Substrate Screening
      Process to Enhance the Sensitivity of Fluorescence-Based Assays in Paper.
AB  - Porous media made of nitrocellulose and glass fiber are common "paper" substrates
      for lateral flow assays, microfluidic paper analytical devices and other point-of
      care diagnostic assays. Such assays commonly use optical labels such as gold
      nanoparticles, latex beads, or fluorescent nanoparticles to visualize the
      presence of analytes. Fluorescent labels are commonly used in bioassays to
      enhance sensitivity, but autoluminescence of the paper substrate worsens signal
      to-noise ratios of fluorescence-based assays. To date, there exists no systematic
      investigation of autoluminescence wavelengths or lifetimes of porous membranes
      used in lateral flow assays. In response, we quantified the autoluminescence of
      commonly used porous materials across the visible spectrum via excitation
      emission spectroscopy and time-resolved fluorescence spectroscopy, and
      demonstrate that autoluminescence is solely due to autofluorescence with
      lifetimes of about 5 ns in the visible spectrum. Counterintuitively, we found
      that spectroscopy alone does not provide sufficient information to select
      candidate paper substrates for fluorophore-labeled assays. Therefore, we
      developed a simple quantitative framework to select a low-fluorescence substrate
      that minimizes both the overlap of paper and fluorophore emission spectra and the
      fluorescence intensity on an imaging system of interest (such as a gel imager).
      Use of this framework was shown to lower the limit of detection of an influenza A
      nucleoprotein immunoassay by over 50%. The tools developed in this manuscript
      enable assay developers to screen appropriate, low-fluorescence porous substrates
      and enhance the sensitivity of membrane-based fluorescence assays.

PMID- 29048156
TI  - Prelithiation Activates Fe2(MoO4)3 Cathode for Rechargeable Hybrid Mg2+/Li+
      Batteries.
AB  - The development of rechargeable Mg-based batteries with a high energy density is
      restricted by the high-voltage cathodes and the parasitic side reactions between
      the battery components and electrolytes operating at relatively high potentials.
      Here, we develop a hybrid Mg2+/Li+ cell using a monoclinic or orthorhombic
      Fe2(MoO4)3 cathode, a Mg anode, and a simple (PhMgCl)2-AlCl3 + LiCl electrolyte.
      Hastelloy-C alloy is proposed as a current collector of high-voltage cathode for
      the hybrid Mg2+/Li+ battery within a Swagelok-type cell. The application of the
      Hastelloy-C alloy current collector breaks the crucial bottleneck of
      incompatibility between the currently available current collectors and
      electrolytes. The hybrid cell features a low voltage polarization between the
      discharge and charge profiles, which is in favor of practical applications. On
      the other hand, because all Li+ ions are supplied by the electrolyte in a hybrid
      Mg2+/Li+ battery, a high Li+ concentration is required to operate at high
      capacities for the hybrid battery. We further show the first-hand evidence about
      the compensation of Li+ ions by simply soaking the cathode in the hybrid
      electrolyte. The prelithiation of Li+ ions into monoclinic Fe2(MoO4)3
      significantly enhances the cycling stability and reversibility.

PMID- 29048157
TI  - Paramagnetic 19F Relaxation Enhancement in Nickel(II) Complexes of N
      Trifluoroethyl Cyclam Derivatives and Cell Labeling for 19F MRI.
AB  - 1,8-Bis(2,2,2-trifluoroethyl)cyclam (te2f) derivatives with two coordinating
      pendant arms involving methylenecarboxylic acid (H2te2f2a), methylenephosphonic
      acid (H4te2f2p), (2-pyridyl)methyl (te2f2py), and 2-aminoethyl arms (te2f2ae) in
      4,11-positions were prepared, and their nickel(II) complexes were investigated as
      possible 19F MR tracers. The solid-state structures of several synthetic
      intermediates, ligands, and all complexes were confirmed by X-ray diffraction
      analysis. The average Ni...F distances were determined to be about 5.2 A. All
      complexes exhibit a trans-III cyclam conformation with pendant arms bound in the
      apical positions. Kinetic inertness of the complexes is increased in the ligand
      order te2f2ae ? te2f < te2f2py ~ H4te2f2p ? H2te2f2a. The [Ni(te2f2a)] complex is
      the most kinetically inert Ni(II) complex reported so far. Paramagnetic divalent
      nickel caused a shortening of 19F NMR relaxation time down to the millisecond
      range. Solubility, stability, and cell toxicity were only satisfactory for the
      [Ni(te2f2p)]2- complex. This complex was visualized by 19F MRI utilizing an
      ultrashort echo time (UTE) imaging pulse sequence, which led to an increase in
      sensitivity gain. Mesenchymal stem cells were successfully loaded with the
      complex (up to 0.925/5.55 pg Ni/F per cell).19F MRI using a UTE pulse sequence
      provided images with a good signal-to-noise ratio within the measurement time, as
      short as tens of minutes. The data thus proved a major sensitivity gain in 19F
      MRI achieved by utilization of the paramagnetic (transition) metal complex as 19F
      MR tracers coupled with the optimal fast imaging protocol.

PMID- 29048158
TI  - Efficient Energy Transfer (EnT) in Pyrene- and Porphyrin-Based Mixed-Ligand Metal
      Organic Frameworks.
AB  - Designing and synthesizing the ordered light-harvesting systems, possessing
      complementary absorption and energy-transfer process between the chromophores,
      are essential steps to accomplish successful mimicking of the natural
      photosynthetic systems. Metal-organic frameworks (MOFs) can be considered as an
      ideal system to achieve this due to their highly ordered structure, superior
      synthetic versatility, and tailorable functionality. Herein, we have synthesized
      the new light-harvesting mixed-ligand MOFs (MLMs, MLM-1-3) via solvothermal
      reactions between a Zr6 cluster and a mixture of appropriate ratio of 1,3,6,8
      tetrakis(p-benzoic acid)pyrene and [5,10,15,20-tetrakis(4-carboxy
      phenyl)porphyrinato]-Zn(II) ligands. The identical symmetry and connectivity of
      the two ligands of the MLMs was the key parameter of successful synthesis as a
      single MOF form, and the ample overlap between the emission spectrum of pyrene
      and the absorption spectrum of porphyrin provided the ideal platform to design an
      efficient-energy transfer (EnT) process within the MLMs. We obtained the
      nanoscale maps of the fluorescence intensities and lifetimes of microsize MLM
      grains for unambiguous visualization of EnT phenomena occurring between two
      ligands in MLMs. Moreover, due to complementary absorption and energy transfer
      between the two ligands in the MLMs, our MLMs performed as superior photoinduced
      singlet-oxygen generators, verifying the enhanced light-harvesting properties of
      the pyrene- and porphyrin-based MLMs.

PMID- 29048159
TI  - Using Printing Orientation for Tuning Fluidic Behavior in Microfluidic Chips Made
      by Fused Deposition Modeling 3D Printing.
AB  - Fluidic behavior in microfluidic devices is dictated by low Reynolds numbers,
      complicating mixing. Here, the effect of the orientation of the extruded filament
      on the fluidic behavior is investigated in fused deposition modeling (FDM)
      printed fluidic devices. Devices were printed with filament orientations at 0
      degrees , 30 degrees , 60 degrees , and 90 degrees  to the direction of the flow.
      The extent of mixing was observed when pumping yellow and blue solutions into the
      inlets of a Y-shaped device, and measuring the extent of mixing of two colored
      solutions under different angles and at flow rates of 25, 50, and 100 MUL/min.
      Fluidic devices printed with filament extruded at 60 degrees  to the flow showed
      the highest mixing efficiency, but results obtained at 30 degrees  suggested more
      complex fluid movement, as the measured degree of mixing decreased along the
      fluidic channel at higher flow rates. To explore this, a device with -37 degrees 
      filament orientation on the top surface was designed to align with the direction
      of the first fluid input channel and +37 degrees  on the bottom surface of the
      channel to align with the direction of the second fluidic input. Results
      indicated a rotational movement of the fluids down the microchannel, which were
      confirmed by computational fluid dynamics. These results demonstrate the impact
      of the filament extrusion direction on fluidic behavior in microfluidic devices
      made by FDM printing. Two chips with laminar flow (0 degrees  filament direction)
      or mixing flow (+37/-37 degrees  filament direction) were used to perform
      isotachophoresis and colorimetric detection of iron in river water, respectively,
      demonstrating the simplicity with which the same device can be tuned for
      different applications simply by controlling the way the device is printed.

PMID- 29048160
TI  - Destruxin A Induces and Binds HSPs in Bombyx mori Bm12 Cells.
AB  - Destruxin A (DA) is a cyclodepsipeptidic mycotoxin isolated from the
      entomopathogenic fungus, Metarhizium anisopliae. It has insecticidal activity
      against host insect's innate immunity system, but the molecular mechanism is not
      yet elucidated. In our previous experiment, four HSPs (heat shock proteins,
      BmHSP70-3, BmHSP75, BmHSP83, and BmHSCP) were characterized from the specific
      protein electrophoretic bands of Bombyx mori Bm12 cell line treated with DA in
      the test of drug affinity responsive target stability (DARTS), which implied that
      these HSPs might be kinds of DA-affinity proteins, or DA induces them up
      regulated expression. Therefore, in current research, the interactions of DA and
      HSPs were explored through analysis of bio-layer interferometry (BLI) employing
      FortBio OcteteQK. The expression levels of HSPs genes were surveyed by
      quantitative real-time polymerase chain reaction (qPCR). The results indicated
      that DA had no interactions with BmHSP70-3, BmHSP75, and BmHSP83, but had
      affinity to BmHSCP with a KD value of 88.1 MUM, in BLI analysis. However, the
      expression levels of all HSPs genes were significantly up-regulated after the
      Bm12 cells were treated by DA. In conclusion, DA can induce the four HSPs
      expression in Bm12 cells, but DA only binds to BmHSCP. Our research provides new
      insights on understanding of the action mechanisms of destruxins.

PMID- 29048161
TI  - Effects of Temperature and Concentration on the Rate of Photobleaching of
      Erythrosine in Water.
AB  - Erythrosine, a popular food dye, undergoes fast O2-sensitive bleaching in water
      when subjected to visible light illumination. In dilute solution, erythrosine
      undergoes photobleaching via first-order kinetics, where the rate of bleaching
      depends critically on the rate of photon absorption and on the concentration of
      dissolved oxygen. Kinetic studies indicate that this inherent bleaching is
      augmented by self-catalysis at higher concentrations of erythrosine and on long
      exposure times. Under the conditions used, bleaching occurs by way of geminate
      attack of singlet molecular oxygen on the chromophore. Despite the complexity of
      the overall photobleaching process, the rate constants associated with both
      inherent and self-catalytic bleaching reactions follow Arrhenius-type behavior,
      allowing the activation parameters to be resolved. Bleaching remains reasonably
      efficient in the solid state, especially if the sample is damp, and provides a
      convenient means by which to construct a simple chemical actinometer.

PMID- 29048162
TI  - Cytochrome c as a Peroxidase: Activation of the Precatalytic Native State by H2O2
      Induced Covalent Modifications.
AB  - In addition to serving as respiratory electron shuttle, ferri-cytochrome c (cyt
      c) acts as a peroxidase; i.e., it catalyzes the oxidation of organic substrates
      by H2O2. This peroxidase function plays a key role during apoptosis. Typical
      peroxidases have a five-coordinate heme with a vacant distal coordination site
      that permits the iron center to interact with H2O2. In contrast, native cyt c is
      six-coordinate, as the distal coordination site is occupied by Met80. It thus
      seems counterintuitive that native cyt c would exhibit peroxidase activity. The
      current work scrutinizes the origin of this structure-function mismatch. Cyt c
      catalyzed peroxidase reactions show an initial lag phase that is consistent with
      the in situ conversion of a precatalyst to an active peroxidase. Using mass
      spectrometry, we demonstrate the occurrence of cyt c self-oxidation in the
      presence of H2O2. The newly generated oxidized proteoforms are shown to possess
      significantly enhanced peroxidase activity. H2O2-induced modifications commence
      with oxidation of Tyr67, followed by permanent displacement of Met80 from the
      heme iron. The actual peroxidase activation step corresponds to subsequent side
      chain carbonylation, likely at Lys72/73. The Tyr67-oxidized/carbonylated protein
      has a vacant distal ligation site, and it represents the true peroxidase-active
      structure of cyt c. Subsequent self-oxidation eventually causes deactivation. It
      appears that this is the first report that identifies H2O2-induced covalent
      modifications as an essential component for the peroxidase activity of "native"
      cyt c.

PMID- 29048163
TI  - LiGaGe2S6: A Chalcogenide with Good Infrared Nonlinear Optical Performance and
      Low Melting Point.
AB  - In this work, we design and synthesize a new chalcogenide LiGaGe2S6 on the basis
      of known infrared (IR) material LiGaS2 by partially substituting Ga with Ge. This
      compound possesses very strong nonlinear (NLO) response (2.5 * LiGaS2) and large
      band gap (3.52 eV), manifesting a better balance between band gap and NLO
      response compared with that for LiGaS2. Moreover, LiGaGe2S6 exhibits a much lower
      melting point (663  degrees C) than that of LiGaS2 (1050  degrees C). This would
      result in the much smaller vapor pressure of sulfur in the fused quartz vessels
      used for the crystal growth, and thus, it should be greatly beneficial to obtain
      the large stoichiometric LiGaGe2S6 single crystal. Our studies demonstrate that
      LiGaGe2S6 is a good candidate material for IR NLO applications.

PMID- 29048164
TI  - Development of a Modular Synthetic Route to (+)-Pleuromutilin, (+)-12-epi
      Mutilins, and Related Structures.
AB  - We describe the development of an enantioselective synthetic route to (+)
      pleuromutilin (1), (+)-12-epi-mutilin, and related derivatives. A key
      hydrindanone was prepared in three steps and 48% overall yield from cyclohex-2-en
      1-one. 1,4-Hydrocyanation provided a nitrile (53%, or 85% based on recovered
      starting material) that was converted to the eneimide 57 in 80% yield by the 1,2
      addition of methyllithium to the nitrile function, cyclization, and in situ
      acylation with di-tert-butyldicarbonate. The eneimide 57 was employed in a 2-fold
      neopentylic coupling reaction with an organolithium reagent derived from the
      alkyl iodides (R)- or (S)-30, which contain the C11-C13 atoms of the target, to
      provide diastereomeric diketones in 60% or 48% yield (for coupling with (R)- or
      (S)-30, respectively). The diketone derived from (S)-30 contains the (S)-C12
      stereochemistry found in pleuromutilin and was elaborated to an alkynylaldehyde.
      Nickel-catalyzed reductive cyclization of this alkynylaldehyde, to construct the
      eight-membered ring of the target, unexpectedly provided a cyclopentene (67%),
      which arises from participation of the C12-alpha-olefin in the transformation.
      The diketone derived from the enantiomeric C12-fragment (R)-30 underwent
      reductive cyclization to provide the desired product in 60% yield. This was
      elaborated to 12-epi-mutilin by a four-step sequence (39% overall). Installation
      of the glycolic acid residue followed by C12 epimerization (Berner et al.
      Monatsh. Chem. 1986, 117, 1073) generated (+)-pleuromutilin (1). (+)-12-epi
      Pleuromutilin and (+)-11,12-di-epi-pleuromutilin were prepared by related
      sequences. This work establishes a convergent entry to the pleuromutilins and
      provides a foundation for the production of novel antibiotics to treat drug
      resistant and Gram-negative infections.

PMID- 29048165
TI  - Dielectric and Ferroelectric Properties of SrTiO3-Bi0.5Na0.5TiO3-BaAl0.5Nb0.5O3
      Lead-Free Ceramics for High-Energy-Storage Applications.
AB  - Pulsed capacitors require high-recoverable energy-storage density (Wrec) and high
      energy-storage efficiency (eta), which can be realized through the selection and
      adjustment of the composition. In this work, (1 - x)SrTiO3-x(0.95Bi0.5Na0.5TiO3
      0.05BaAl0.5Nb0.5O3) [(1 - x)ST-x(BNT-BAN)] ceramics were successfully prepared
      via the pressureless solid-state reaction method. The dielectric constant
      increases gradually with the introduction of BNT-BAN and obtains a maximum value
      of 3430 with the composition of 0.4ST-0.6(BNT-BAN) at 100 Hz, which is 10.39
      times higher than that of the pure ST sample (~330). Dispersive relaxor behaviors
      and ferroelectric performances can be enhanced with the introduction of BNT-BAN.
      The composition of 0.5ST-0.5(BNT-BAN) exhibits a high Wrec of 1.89 J/cm3 as well
      as a high eta of 77%. Therefore, the (1 - x)ST-x(BNT-BAN) systems are candidate
      materials for pulsed capacitor applications.

PMID- 29048166
TI  - Atomistic Explanation for Interlayer Charge Transfer in Metal-Semiconductor
      Nanocomposites: The Case of Silver and Anatase.
AB  - A concerted theoretical and experimental investigation of the silver/anatase
      hybrid nanocomposite, a very promising material for advanced sensing
      applications, is presented. We measure its exceptional electrochemical virtues in
      terms of current densities and reproducibility, providing their explanation at
      the atomic-scale level and demonstrating how and why silver acts as a positive
      electrode. Using periodic plane-wave DFT calculations, we estimate the overall
      amount of electron transfer toward the semiconductor side of the interface at
      equilibrium. Suitably designed (photo)electrochemical experiments strictly agree,
      both qualitatively and quantitatively, with the theoretical charge transfer
      estimates. The unique permanent charge separation occurring in the device is
      possible because of the favorable synergy of Ag and TiO2, which exploits in a
      favorable band alignment, while the electron-hole recombination rate and carrier
      mobility decrease when electrons cross the metal-semiconductor interface.
      Finally, the hybrid material is proven to be extremely robust against aging,
      showing complete regeneration, even after 1 year.

PMID- 29048167
TI  - Toroidal Droplets: Growth Rates, Dispersion Relations, and Behavior in the Thick
      Torus Limit.
AB  - Toroidal droplets in a viscous liquid are unstable and transform into single or
      multiple spherical droplets. For thin tori, this can happen via the Rayleigh
      Plateau instability causing the breakup of cylindrical jets. In contrast, for
      thick tori, this can happpen via the shrinking of the "hole". In this work, we
      use the thin-torus limit to directly measure the growth rate associated with
      capillary disturbances. In the case of toroidal droplets inside a much more
      viscous liquid, we even obtain the full dispersion relation, which is in
      agreement with theoretical results for cylindrical jets. For thick tori, we
      employ particle image velocimetry to determine the flow field of a sinking
      toroidal drop inside another viscous liquid. We find that the presence of the
      "hole" greatly suppresses one of the circulation loops expected for sinking
      cylinders. Finally, using the flow field of a shrinking toroidal droplet and the
      time-reversal symmetry of the Stokes equations, we theoretically predict the
      expected shape deformation of an expanding torus and confirm the result
      experimentally using charged toroidal droplets.

PMID- 29048168
TI  - Comment on The Ecstasy and Agony of Assay Interference Compounds.
AB  - : A recent editorial (Aldrich et al. The Ecstasy and Agony of Assay Interference
      Compounds . J. Chem. Inf. MODEL: 2017 , 57 , 387 - 390 ) is examined critically.
      When assessing assay hits from screening, it is important to draw a distinction
      between false positives, that have no effect on target function, and compounds
      that affect target function through an undesirable mechanism of action.
      Observation of frequent-hitter behavior for a compound should be regarded as
      circumstantial evidence, rather than definitive proof, that the compound has
      interfered with assay readouts or acted through an undesirable mechanism of
      action. The applicability domain of published (Baell and Holloway J. Med. Chem.
      2010 , 53 , 2719 - 2740 ) Pan Assay INterference compoundS (PAINS) filters is
      limited by the narrow scope of the proprietary data used to derive them. It is
      suggested that journal guidelines for authors should not prescribe, as those for
      the Journal of Medicinal Chemistry appear to do, that activity in assays reported
      for compounds that match PAINS filters be treated any differently from that for
      compounds that do not match PAINS filters. It is argued that use of models based
      on proprietary data in the evaluation of manuscripts would contradict the
      editorial policy of any journal that deemed the use of proprietary data to be
      unacceptable in modeling studies.

PMID- 29048170
TI  - Total Synthesis of (+)-Pochonin D and (+)-Monocillin II via Chemo- and
      Regioselective Intramolecular Nitrile Oxide Cycloaddition.
AB  - Asymmetric total syntheses of (+)-pochonin D (1) and (+)-monocillin II (2), Hsp90
      inhibitors with potent anticancer activity, have been accomplished where the
      macrolactone 3 was constructed through a chemo- and regioselective intramolecular
      nitrile oxide cycloaddition of diene 4.

PMID- 29048169
TI  - Photoactivity of New Octacationic Magnesium(II) and Zinc(II) Porphyrazines in a
      Water Solution and G-Quadruplex Binding Ability of Differently Sized Zinc(II)
      Porphyrazines.
AB  - The new octacations [(2-Mepy)8PzM]8+ [M = MgII(H2O), ZnII], isolated as iodide
      salts, were obtained from the corresponding neutral complexes [Py8PzM] (Py = 2
      pyridyl; Pz = porphyrazinato dianion) upon quaternization with CH3I of the N
      atoms of the 2-pyridyl rings under mild experimental conditions. The absorption
      spectra registered in organic solvents as well as in water (H2O) confirm the
      presence of the complexes in their monomeric form in all cases. The two
      octacations behave as photosensitizers in a H2O/sodium dodecyl sulfate solution
      for the production of singlet oxygen, 1O2, and exhibit quantum yield values
      (PhiDelta) 2.2-2.5 higher than those measured for the standard PcAlSmix, a
      promising feature of interest for photodynamic therapy. The interaction of the
      ZnII octacation [(2-Mepy)8PzZn]8+ with different types of DNA has been studied by
      means of optical spectroscopic techniques, clearly suggesting that binding of the
      charged macrocycle to the DNA effectively takes place. In order to assess the
      effect of the aromatic ring size, the same binding study was performed for the
      octapyridinated zinc(II) tetraquinoxalinoporphyrazine complex having a much more
      expanded macrocyclic framework and compared with the behavior of the parent
      octapyridinated zinc(II) tetrapyrazinoporphyrazine complex having an intermediate
      macrocycle. The achieved information confirms the relationship between the
      binding of the charged macrocycle to the DNA and the dimension of the
      porphyrazine macrocycle.

PMID- 29048171
TI  - AFM Colloidal Probe Measurements Implicate Capillary Condensation in Punch
      Particle Surface Interactions during Tableting.
AB  - Adhesion of the powders to the punches is a common issue during tableting. This
      phenomenon is known as sticking and affects the quality of the manufactured
      tablets. Defective tablets increase the cost of the manufacturing process. Thus,
      the ability to predict the tableting performance of the formulation blend before
      the process is scaled-up is important. The adhesive propensity of the powder to
      the tableting tools is mostly governed by the surface-surface adhesive
      interactions. Atomic force microscopy (AFM) colloidal probe is a surface
      characterization technique that allows the measurement of the adhesive
      interactions between two materials of interest. In this study, AFM steel
      colloidal probe measurements were performed on ibuprofen, MCC (microcrystalline
      cellulose), alpha-lactose monohydrate, and spray-dried lactose particles as an
      approach to modeling the punch-particle surface interactions during tableting.
      The excipients (lactose and MCC) showed constant, small, attractive, and adhesive
      forces toward the steel surface after a repeated number of contacts. In
      comparison, ibuprofen displayed a much larger attractive and adhesive interaction
      increasing over time both in magnitude and in jump-in/jump-out separation
      distance. The type of interaction acting on the excipient-steel interface can be
      related to a van der Waals force, which is relatively weak and short-ranged. By
      contrast, the ibuprofen-steel interaction is described by a capillary force
      profile. Even though ibuprofen is not highly hydrophilic, the relatively smooth
      surfaces of the crystals allow "contact flooding" upon contact with the steel
      probe. Capillary forces increase because of the "harvesting" of moisture-due to
      the fast condensation kinetics-leaving a residual condensate that contributes to
      increase the interaction force after each consecutive contact. Local asperity
      contacts on the more hydrophilic surface of the excipients prevent the flooding
      of the contact zone, and there is no such adhesive effect under the same ambient
      conditions. The markedly different behavior detected by force measurements
      clearly shows the sticky and nonsticky propensity of the materials and allows a
      mechanistic description.

PMID- 29048172
TI  - Effects of Different Lipophilized Ferulate Esters in Fish Oil-Enriched Milk:
      Partitioning, Interaction, Protein, and Lipid Oxidation.
AB  - Antioxidant effects of ferulic acid and lipophilized ferulate esters were
      investigated in fish oil-enriched milk. Methyl ferulate (C1) and ethyl ferulate
      (C2) more efficiently prevented lipid oxidation than dodecyl ferulate (C12) did,
      followed by ferulic acid (C0). The combination of C1 or C2 with C12 could have a
      "synergistic" effect indicated by peroxide value, hexanal, and 1-penten-3-ol
      analysis results. These antioxidants also showed protein oxidation inhibition
      effects. The most effective antioxidants (C1 and C2) had the highest
      concentration in the precipitate phase but the lowest concentration in the
      aqueous phase, which was the opposite of the partitioning of C0. C12 had the
      highest concentration in the oil and emulsion phase. In particular, the
      interaction between ferulates esterified with short and medium alkyl chain
      lengths could lead to their "synergistic" effects in fish oil-enriched milk,
      which could be caused by the change in their partitioning or localization at the
      interface.

PMID- 29048173
TI  - Family of Polynuclear Nickel Cagelike Phenylsilsesquioxanes; Features of Periodic
      Networks and Magnetic Properties.
AB  - A new family of bi-, tetra-, penta-, and hexanickel cagelike
      phenylsilsesquioxanes 1-6 was obtained by self-assembly and transmetalation
      procedures. Their crystal structures were established by single-crystal X-ray
      analysis, and features of crystal packing relevant to the network formation were
      studied by a topological analysis. Compounds 1, 2, and 4 are isolated
      architectures, while 3, 5, and 6 present extended 1D and 3D networks. The
      investigation of magnetic properties revealed the presence of ferro- (1 and 3-5)
      or antiferromagnetic (2 and 6) interactions between Ni(II) ions, giving rise in
      the most cases (1, 2, and 4-6) to the presence of a slow relaxation of the
      magnetization, which can originate from the spin frustration.

PMID- 29048174
TI  - Rare-Earth-Incorporated Tellurotungstate Hybrids Functionalized by 2-Picolinic
      Acid Ligands: Syntheses, Structures, and Properties.
AB  - A series of organic-inorganic rare-earth-incorporated tellurotungstate hybrids,
      Na4[RE2(H2O)4(pica)2W2O5][(RE(H2O)W2(Hpica)2O4)(B-beta-TeW8O30H2)2]2.38H2O (RE =
      LaIII (1), CeIII (2), NdIII (3), SmIII (4), EuIII (5); Hpica = 2-picolinic acid),
      were prepared via a one-step assembly reaction of Na2WO4.2H2O, RE(NO3)3.6H2O,
      K2TeO3, Hpica, and triethylamine (tea). Notably, the solubilization of tea toward
      Hpica and the solubilization of Hpica toward RE cations in the reaction system
      play an important role in the formation of 1-5. The most significant feature of 1
      5 consists of an intriguing tetrameric
      [RE2(H2O)4(pica)2W2O5][(RE(H2O)W2(Hpica)2O4)(B-beta-TeW8O30H2)2]24- polyoxoanion
      constructed from two tetravacant Keggin sandwich-type [(RE(H2O)W2(Hpica)2O4)(B
      beta-TeW8O30H2)2]5- entities linked by a RE-W-Hpica {RE2(H2O)4(pica)2W2O5}6+
      cluster, in which Hpica ligands not only play a key bridging role in linking RE
      and W centers by carboxylic groups in an irregular N-O-RE-O-W-O six-membered-ring
      motif but also can directly chelate with W centers via N and O atoms in a stable
      N-O-C-O-W five-membered-ring fashion. 1-5 represent rare organic-inorganic hybrid
      RE-substituted tellurotungstates. Moreover, the solid-state photoluminescence
      properties of 3-5 have been deeply investigated, and these compounds exhibit the
      characteristic emission stemming from intra-4f transitions of RE ions. The energy
      transfer of the O -> W transitions sensitizing the emission of SmIII centers in 4
      is convincingly proved by time-resolved emission spectra (TRES); the increase in
      the strongest typical emission of SmIII ions at a decay time of 17 MUs is
      accompanied by the decline of O -> W emission, and the CIE 1931 diagram was
      obtained from the corresponding TRES. Furthermore, a comparison of the
      luminescence behaviors of 5 in the solid state and in solution reveals the
      structural skeletal integrity of 5 in solution and a shorter decay lifetime in
      the solution caused by the high-frequency O-H oscillators.

PMID- 29048175
TI  - Testing a continuum structure of self-determined motivation: A meta-analysis.
AB  - Self-determination theory proposes a multidimensional representation of
      motivation comprised of several factors said to fall along a continuum of
      relative autonomy. The current meta-analysis examined the relationships between
      these motivation factors in order to demonstrate how reliably they conformed to a
      predictable continuum-like pattern. Based on data from 486 samples representing
      over 205,000 participants who completed 1 of 13 validated motivation scales, the
      results largely supported a continuum-like structure of motivation and indicate
      that self-determination is central in explaining human motivation. Further
      examination of heterogeneity indicated that while regulations were predictably
      ordered across domains and scales, the exact distance between subscales varied
      across samples in a way that was not explainable by a set of moderators. Results
      did not support the inclusion of integrated regulation or the 3 subscales of
      intrinsic motivation (i.e., intrinsic motivation to know, to experience
      stimulation, and to achieve) due to excessively high interfactor correlations and
      overlapping confidence intervals. Recommendations for scale refinements and the
      scoring of motivation are provided. (PsycINFO Database Record

PMID- 29048176
TI  - Meta-analysis of the effect of natural frequencies on Bayesian reasoning.
AB  - The natural frequency facilitation effect describes the finding that people are
      better able to solve descriptive Bayesian inference tasks when represented as
      joint frequencies obtained through natural sampling, known as natural
      frequencies, than as conditional probabilities. The present meta-analysis reviews
      20 years of research seeking to address when, why, and for whom natural frequency
      formats are most effective. We review contributions from research associated with
      the 2 dominant theoretical perspectives, the ecological rationality framework and
      nested-sets theory, and test potential moderators of the effect. A systematic
      review of relevant literature yielded 35 articles representing 226 performance
      estimates. These estimates were statistically integrated using a bivariate mixed
      effects model that yields summary estimates of average performances across the 2
      formats and estimates of the effects of different study characteristics on
      performance. These study characteristics range from moderators representing
      individual characteristics (e.g., numeracy, expertise), to methodological
      differences (e.g., use of incentives, scoring criteria) and features of problem
      representation (e.g., short menu format, visual aid). Short menu formats (less
      computationally complex representations showing joint-events) and visual aids
      demonstrated some of the strongest moderation effects, improving performance for
      both conditional probability and natural frequency formats. A number of
      methodological factors (e.g., exposure to both problem formats) were also found
      to affect performance rates, emphasizing the importance of a systematic approach.
      We suggest how research on Bayesian reasoning can be strengthened by broadening
      the definition of successful Bayesian reasoning to incorporate choice and process
      and by applying different research methodologies. (PsycINFO Database Record

PMID- 29048178
TI  - The uncertainty of psychological and psychiatric diagnoses.
AB  - Psychiatric and psychological diagnoses are imperfect. Unlike somatic medicine,
      most psychological and psychiatric phenomena have no gold standard to establish
      their presence beyond reasonable doubt. Consequently, prevalence estimates are
      based on the average agreement of imperfect evaluators. Kuchenhoff, Augustin, and
      Kunz (2012) provided a statistical method for estimating confidence intervals of
      the prevalence based on the well-known kappa coefficient of interrater agreement.
      We expand this method and derive confidence intervals for the probability of a
      diagnosis being true (i.e., the positive predictive value). We illustrate the
      method and its results with empirical data for a particular type of paraphilia
      (pedophilia) in sexual offenders. The findings indicate that up to 1 in 3
      diagnoses of pedophilia may be wrong. Given the similar rates of prevalence and
      interrater agreement reported for diagnoses in general psychiatry (such as
      schizophrenia or affective disorders), the results likely apply to other
      diagnostic domains as well. (PsycINFO Database Record

PMID- 29048177
TI  - The role of a palliative care intervention in moderating the relationship between
      depression and survival among individuals with advanced cancer.
AB  - OBJECTIVE: Randomized controlled trials (RCTs) of early palliative care
      interventions in advanced cancer have positively impacted patient survival, yet
      the mechanisms remain unknown. This secondary analysis of 2 RCTs assessed whether
      an early palliative care intervention moderates the relationship between
      depressive symptoms and survival. METHOD: The relationships among mood, survival,
      and early palliative care intervention were studied among 529 advanced cancer
      patients who participated in 2 RCTs. The first (N = 322) compared intervention
      versus usual care. The second (N = 207) compared early versus delayed
      intervention (12 weeks after enrollment). The interventions included an in-person
      consultation, weekly nurse coach-facilitated phone sessions, and monthly follow
      up. Mood was measured using the Center for Epidemiologic Studies-Depression (CES
      D) scale. Cox proportional hazard analyses were used to examine the effects of
      baseline CES-D scores, the intervention, and their interaction on mortality risk
      while controlling for demographic variables, cancer site, and illness severity.
      RESULTS: The combined sample was 56% male (M = 64.7 years). Higher baseline CES-D
      scores were significantly associated with greater mortality risk (hazard ratio
      [HR] = 1.042, 95% confidence interval [CI] [1.017, 1.067], p = .001). However,
      participants with higher CES-D scores who received the intervention had a lower
      mortality risk (HR = .963, CI [0.933, 0.993], p = .018) even when controlling for
      demographics, cancer site, and illness-related variables. CONCLUSION: This study
      is the first to demonstrate that patients with advanced cancer who also have
      depressive symptoms benefit the most from early palliative care. Future research
      should be devoted to exploring the mechanisms responsible for these
      relationships. (PsycINFO Database Record

PMID- 29048179
TI  - Constellations of dyadic relationship quality in stepfamilies: A factor mixture
      model.
AB  - Stepfamilies are an increasingly common family form, marked by distinct
      challenges, opportunities, and complex networks of dyadic relationships that can
      transcend single households. There exists a dearth of typological analyses by
      which constellations of dyadic processes in stepfamilies are holistically
      analyzed. Factor mixture modeling is used to identify population heterogeneity
      with respect to features of mother-child, stepfather-child, nonresident father
      child, and stepcouple relationships using a representative sample of 1,182
      adolescents in mother-stepfather families with living nonresident fathers from
      Wave I of the National Longitudinal Study of Adolescent to Adult Health. Results
      favor a 4-class factor-mixture solution with class-specific factor covariance
      matrices. Class 1 (n = 302, 25.5%), the residence-centered pattern, was marked by
      high-quality residential relationships. Class 2 (n = 307, 26%), the inclusive
      pattern, was marked by high-quality relationships across all four dyads, with an
      especially involved nonresident father-child relationship. Class 3 (n = 350,
      29.6%), the unhappy couple pattern, was marked by very low stepcouple
      relationship quality. Class 4 (n = 223, 18.9%), the parent-child disconnection
      pattern, was marked by distant relationships between youth and all three parental
      figures. The residence-centered and inclusive patterns encompassed some positive
      correlations between dyadic relationships whereas the unhappy couple and parent
      child disconnection patterns encompassed some negative correlations between
      dyadic relationships. The patterns present with differences across
      sociodemographic and substantive covariates and highlight important opportunities
      for the development of new and innovative interventions, particularly to meet the
      needs of stepfamilies that reflect the parent-child disconnection pattern.
      (PsycINFO Database Record

PMID- 29048180
TI  - "Meta-analyses and P-curves support robust cycle shifts in women's mate
      preferences: Reply to Wood and Carden (2014) and Harris, Pashler, and Mickes
      (2014)": Correction to Gildersleeve, Haselton, and Fales (2014).
AB  - Reports an error in "Meta-analyses and p-curves support robust cycle shifts in
      women's mate preferences: Reply to Wood and Carden (2014) and Harris, Pashler,
      and Mickes (2014)" by Kelly Gildersleeve, Martie G. Haselton and Melissa R. Fales
      (Psychological Bulletin, 2014[Sep], Vol 140[5], 1272-1280). In the article, all p
      curve analyses examining the Context Moderation Hypothesis Prediction mistakenly
      included the p-value from Little, Jones, Burt, & Perrett (2007) Study 2 for the
      simple effect of fertility on attraction to facial symmetry in a short-term
      relationship context (p < .001). The analyses should have instead included the p
      value for the fertility X relationship context interaction (p = .011). In
      addition, the p-curve analyses examining exact two-tailed p-values for the Cycle
      Shift Prediction should have included an additional p-value from Provost et al.
      (2008) Study 1 for the main effect of fertility on attraction to gait
      masculinity. The reported p-value for this effect was .05, making it ineligible
      for inclusion in p-curves of reported p-values. However, the exact recalculated
      two-tailed p-value was .049, making it eligible for inclusion in p-curves of
      exact p-values. The corrected p-curve of exact two-tailed p-values evaluating the
      Cycle Shift Prediction and Context Moderation Prediction (displayed in Figure 2)
      now includes a total of 15 p-values (N = 1442) is no longer significantly right
      skewed chi2(30) = 41.25, p = .08. The corrected p-curve of exact two-tailed p
      values evaluating the Cycle Shift Prediction, Context Moderation Prediction, and
      Partner Qualities Moderation Prediction (displayed in Figure 3) now includes a
      total of 21 p-values (N = 1707) and continues to be significantly right skewed
      Chi2(42) = 69.83, p = .004. As part of this correction, the online supplemental
      materials have been updated. (The following abstract of the original article
      appeared in record 2014-35938-003.) Two meta-analyses evaluated shifts across the
      ovulatory cycle in women's mate preferences but reported very different findings.
      In this journal, we reported robust evidence for the pattern of cycle shifts
      predicted by the ovulatory shift hypothesis (Gildersleeve, Haselton, & Fales,
      2014). However, Wood, Kressel, Joshi, and Louie (2014) claimed an absence of
      compelling support for this hypothesis and asserted that the few significant
      cycle shifts they observed were false positives resulting from publication bias,
      p-hacking, or other research artifacts. How could 2 meta-analyses of the same
      literature reach such different conclusions? We reanalyzed the data compiled by
      Wood et al. These analyses revealed problems in Wood et al.'s meta-analysis-some
      of which are reproduced in Wood and Carden's (2014) comment in the current issue
      of this journal-that led them to overlook clear evidence for the ovulatory shift
      hypothesis in their own set of effects. In addition, we present right-skewed p
      curves that directly contradict speculations by Wood et al.; Wood and Carden; and
      Harris, Pashler, and Mickes (2014) that supportive findings in the cycle shift
      literature are false positives. Therefore, evidence from both of the meta
      analyses and the p-curves strongly supports genuine, robust effects consistent
      with the ovulatory shift hypothesis and contradicts claims that these effects
      merely reflect publication bias, p-hacking, or other research artifacts.
      Unfounded speculations about p-hacking distort the research record and risk
      unfairly damaging researchers' reputations; they should therefore be made only on
      the basis of firm evidence. (PsycINFO Database Record

PMID- 29048181
TI  - An open-label pilot study of an intervention using mobile phones to deliver
      contingency management of tobacco abstinence to high school students.
AB  - This pilot study assessed the feasibility, acceptability, and preliminary
      efficacy of a smoking cessation intervention that used mobile phones to remotely
      deliver reinforcements contingent on tobacco abstinence (contingency management
      [CM]) and weekly in-person cognitive-behavioral therapy to adolescent smokers.
      Daily adolescent smokers (N = 15; 12 completed study procedures, 3 dropped out)
      were recruited to participate in a 4-week study. During the first 2 weeks, daily
      text messages sent at random times prompted participants to transmit a video of
      themselves providing a carbon monoxide (CO) sample. During the last 2 weeks, text
      messages sent on 3 randomly chosen days each week prompted participants to
      transmit a video of themselves providing a saliva sample. Negative samples (CO
      <=8 ppm; cotinine <=100 ng/ml) were reinforced with monetary incentives.
      Feasibility was assessed using the number of on-time, valid videos, and
      acceptability was determined using participant perceptions of the intervention.
      Seven-day point-prevalence (PP) abstinence (self-reported abstinence, cotinine
      <100 ng/ml) was assessed at end of treatment (EOT) and at a 1-month follow-up.
      The study findings indicate that remote delivery of CM using mobile phones was
      feasible (85.8% of the CO videos and 67% of the saliva cotinine videos were on
      time) and acceptable (positive perceptions of the CM procedures). Seven-day PP
      was 60% at EOT and 46.7% at the follow-up. Although larger randomized controlled
      trials are needed to evaluate efficacy, this pilot study suggests that the use of
      mobile phones to deliver CM for smoking cessation among adolescent smokers was
      acceptable and feasible. (PsycINFO Database Record

PMID- 29048183
TI  - An initial study of behavioral addiction symptom severity and demand for indoor
      tanning.
AB  - Indoor tanning remains a popular activity in Western cultures despite a growing
      body of literature suggesting its link to skin cancer and melanoma. Advances in
      indoor tanning research have illuminated problematic patterns of its use. With
      problems such as difficulty quitting, devoting resources toward its use at the
      expense of healthy activities, and excessive motivation and urges to tan,
      symptoms of excessive indoor tanning appear consistent with behavioral addiction.
      The present study bridges the gap between clinical approaches to understanding
      indoor tanning problems and behavioral economic considerations of unhealthy
      habits and addiction. Eighty undergraduate females completed both the Behavioral
      Addiction Indoor Tanning Screener and the Tanning Purchase Task. Results suggest
      that behavioral economic demand for tanning significantly differs between risk
      classification groups, providing divergent validity to the Behavioral Addiction
      Indoor Tanning Screener and offering additional evidence of the sensitivity of
      the Tanning Purchase Task to differentiating groups according to tanning
      profiles. (PsycINFO Database Record

PMID- 29048182
TI  - Differences in mood and cortisol by menstrual phase during acute smoking
      abstinence: A within-subject comparison.
AB  - There is evidence that smoking-cessation success differs by menstrual phase and
      sex hormone levels; however, the biological mechanisms underlying these
      differences are not clear. One possibility is that variation in cortisol
      throughout the menstrual cycle and early smoking abstinence may be partly
      responsible. The goal of this secondary-data analysis was to conduct a within
      subject examination of the effects of menstrual phase and smoking abstinence on
      salivary cortisol and mood. Data are from a controlled crossover trial, in which
      participants completed 2 testing weeks during their follicular and luteal phases.
      During each testing week, they smoked ad libitum during the first 2 days and then
      abstained from smoking during the next 4 days. Salivary cortisol and self
      reported mood were collected 5 times on the day before abstinence (D0) and the
      first (D1) and third (D3) days of abstinence. Participants (n = 125) were, on
      average (mean +/- SE), 29.4 +/- 0.6 years old and smoked 12.6 +/- 0.5
      cigarettes/day. Whereas salivary cortisol varied significantly by time of day (p
      < .0001) and smoking abstinence (D0 to D1: beta = -0.06 +/- 0.02 log[ng/ml], p =
      .0074 and D3: beta = -0.05 +/- 0.02 log[ng/ml], p = .0117). no significant
      differences by menstrual phase were observed. Craving increased from D0 to D1
      during the follicular phase but decreased in the luteal phase (+0.31 vs. -0.15,
      beta = 0.46 +/- 0.19, p = .0162). This work builds on prior observations in
      demonstrating a decrease in cortisol in acute smoking abstinence and menstrual
      phase differences in craving. The results provide further evidence that cortisol
      levels do not vary by menstrual phase in the first few days of abstinence.
      (PsycINFO Database Record

PMID- 29048184
TI  - Association of nicotine metabolism and sex with relapse following varenicline and
      nicotine replacement therapy.
AB  - Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine,
      mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of
      varenicline in women and in nicotine normal metabolizers phenotypically
      determined by nicotine-metabolite ratio. Our objective was to study the influence
      of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine
      replacement therapy and varenicline. Data were extracted from a longitudinal
      study which included smokers participating in a smoking cessation program.
      Response to treatment was defined by the absence of relapse when a set threshold
      of reduction in cigarettes per day relative to the week before the study was no
      more reached. The analysis considered total and partial reduction defined by a
      diminution of 100% and of 90% in cigarettes per day, respectively. The hazard
      ratio of relapsing was estimated in multivariate Cox regression models including
      the sex and the nicotine metabolism determined by the phenotype or by CYP2A6
      genotyping (rs1801272 and rs28399433). In the normal metabolizers determined by
      phenotyping and in women, the hazard ratio for relapsing was significantly lower
      with varenicline for a partial decrease (HR = 0.33, 95% CI [0.12, 0.89] and HR =
      0.20, 95% CI [0.04, 0.91], respectively) and nonsignificantly lower for a total
      cessation (HR = 0.45, 95% CI [0.20, 1.0] and HR = 0.38, 95% CI [0.14, 1.0]). When
      compared with the normal metabolizers determined by phenotyping, the hazard ratio
      for a partial decrease was similar in the normal metabolizers determined by
      genotyping (HR = 0.42, 95% CI [0.18, 0.94]) while it was significantly lower with
      varenicline for a total cessation (HR = 0.50, 95% CI [0.26, 0.98]). Women and
      normal nicotine metabolizers may benefit more from varenicline over nicotine
      replacement therapy. (PsycINFO Database Record

PMID- 29048185
TI  - Impulsivity and approach tendencies towards cigarette stimuli: Implications for
      cigarette smoking and cessation behaviors among youth.
AB  - Impulsivity is associated with smoking, difficulties quitting smoking, and
      approach tendencies toward cigarette stimuli among adolescents. We examined the
      effects of impulsivity on (a) the association between approach tendencies and
      adolescents' smoking status and (b) the effectiveness of Cognitive Bias
      Modification (CBM), a smoking cessation intervention focused on changing approach
      tendencies, among adolescent smokers. We conducted a secondary analysis of
      evidence from 2 previous published studies: Study 1: a cross-sectional study
      comparing impulsivity and approach tendencies between adolescent smokers (n = 67)
      and nonsmokers (n = 58); Study 2: a treatment study that randomized 60 adolescent
      smokers to receive either CBM or sham training. Impulsivity was measured using
      the Barratt Impulsiveness Scale (BIS) and the Experiential Discounting Task
      (EDT). We found higher impulsivity, as determined by the BIS but not the EDT,
      increased adolescents' odds of being smokers. We observed that the interaction
      between EDT and approach tendencies also significantly predicted smoking status,
      however post hoc comparisons were not significant. Adolescents with higher BIS
      scores receiving CBM had increased odds of being abstinent at the end of
      treatment, but we found no association between EDT and treatment outcome. Our
      findings suggest that approach-bias modification (a form of CBM) may be more
      effective in impulsive adolescent smokers. Differences in findings for BIS and
      EDT highlight the complexity of the construct of impulsivity. Future studies with
      larger samples are needed to further disentangle the effects of different aspects
      of impulsivity on smoking behaviors and cessation outcomes among youth. (PsycINFO
      Database Record

PMID- 29048186
TI  - Toward a laboratory model for psychotherapeutic treatment screening:
      Implementation intentions and incentives for abstinence in an analog of smoking
      relapse.
AB  - Despite reductions in cigarette smoking in the United States, approximately 40
      million Americans are smokers. Innovative interventions are needed to help
      remaining smokers quit. To develop innovative interventions, precise and
      effective tools are needed. Here, a laboratory model of smoking relapse is
      assessed for its ability to detect increased resistance to smoking across 2
      interventions and for its sensitivity to differing degrees of effectiveness.
      Nicotine-deprived participants (N = 36) completed, in randomized order, 4 smoking
      resistance sessions with and without implementation intentions and monetary
      incentives. A Cox proportional hazard mixed-effects model indicated significant
      differences between condition, chi2(3) = 64.87, p < .001, and the Questionnaire
      on Smoking Urges, chi2(1) = 4.86, p = .03. Comparisons between conditions were
      used to estimate the effect size of each condition on delay to smoking
      reinitiation. The implementation intentions intervention had a small effect (d =
      0.32), the monetary incentives had a large effect (d = 0.89) and the combination
      of both interventions had a large effect size (d = 1.20). This initial
      investigation of the smoking resistance paradigm showed sensitivity to smoking
      reinitiation across intervention conditions. Individuals resisted smoking
      significantly more in the presence of monetary incentives and implementation
      intentions than without these interventions. These results provide support for
      further examination of these interventions in more translational settings and the
      use of this laboratory analog to screen future interventions and treatment
      packages. (PsycINFO Database Record

PMID- 29048187
TI  - Electronic cigarette user plasma nicotine concentration, puff topography, heart
      rate, and subjective effects: Influence of liquid nicotine concentration and user
      experience.
AB  - Electronic cigarette (ECIG) nicotine delivery and other effects may depend on
      liquid nicotine concentration and user experience. This study is the first to
      systematically examine the influence of ECIG liquid nicotine concentration and
      user experience on nicotine delivery, heart rate, puff topography, and subjective
      effects. Thirty-three ECIG-experienced individuals and 31 ECIG-naive cigarette
      smokers completed 4 laboratory conditions consisting of 2, 10-puff bouts (30-sec
      interpuff interval) with a 3.3-V ECIG battery attached to a 1.5-Omega
      "cartomizer" (7.3 W) filled with 1 ml ECIG liquid. Conditions differed by liquid
      nicotine concentration: 0, 8, 18, or 36 mg/ml. Participants' plasma nicotine
      concentration was directly related to liquid nicotine concentration and dependent
      on user experience, with significantly higher mean plasma nicotine increases
      observed in ECIG-experienced individuals relative to ECIG-naive smokers in each
      active nicotine condition. When using 36 mg/ml, mean plasma nicotine increase for
      ECIG-experienced individuals was 17.9 ng/ml (SD = 17.2) and 6.9 (SD = 7.1; p <
      .05) for ECIG-naive individuals. Between-group differences were likely due to
      longer puffs taken by experienced ECIG users: collapsed across condition, mean
      puff duration was 5.6 sec (SD = 3.0) for ECIG-experienced and 2.9 (SD = 1.5) for
      ECIG-naive individuals. ECIG use also suppressed nicotine/tobacco abstinence
      symptoms in both groups; the magnitude of abstinence symptom suppression depended
      on liquid nicotine concentration and user experience. These and other recent
      results suggest that policies intended to limit ECIG nicotine delivery will need
      to account for factors in addition to liquid nicotine concentration (e.g., device
      power and user behavior). (PsycINFO Database Record

PMID- 29048188
TI  - Effects of environmental enrichment on d-amphetamine self-administration
      following nicotine exposure.
AB  - Adolescent nicotine exposure has been shown to lead to further psychostimulant
      use in adulthood. Previous preclinical research in rats has shown that
      environmental enrichment may protect against drug abuse vulnerability. The
      current study was designed to examine whether environmental enrichment can block
      the ability of adolescent nicotine exposure to increase d-amphetamine self
      administration in adulthood. Male Sprague-Dawley rats were raised in either
      enriched conditions (ECs) or isolated conditions (ICs) and then injected with
      saline or nicotine (0.4 mg/kg, sc) for 7 days during adolescence. In adulthood
      rats were allowed to self-administer d-amphetamine under a fixed ratio (FR; 0,
      0.006, 0.01, 0.02, 0.06, and 0.1 mg/kg/infusion) and progressive ratio (PR; 0,
      0.006, 0.06, and 0.1 mg/kg/infusion) schedule of reinforcement. Nicotine-treated
      IC rats self-administered more d-amphetamine at 0.006, 0.01, and 0.02
      mg/kg/infusion doses compared with their saline-treated IC counterparts
      regardless of the schedule maintaining behavior. This effect of nicotine was
      reversed in EC rats on a fixed ratio schedule. These findings indicate that
      environmental enrichment can limit the ability of adolescent nicotine exposure to
      increase vulnerability to other psychostimulant drugs, such as d-amphetamine.
      (PsycINFO Database Record

PMID- 29048189
TI  - Sex-related marijuana expectancies as predictors of sexual risk behavior
      following smoked marijuana challenge.
AB  - Marijuana use has been associated with sexual risk behavior, but the mechanisms
      that underlie this relationship are not well understood. The present study
      examined whether marijuana acutely increased sexual risk on a behavioral decision
      making task and whether sex-related marijuana outcome expectancies influenced
      sexual risk decisions after marijuana administration. Participants were
      heterosexual marijuana users (n = 126) who were randomly assigned to 1 of 4 study
      conditions using a 2 * 2 factorial design crossing drug administration (received
      2.8% delta-9-tetrahydrocannabinol [THC] or 0% THC) with instructional set (told
      THC or told placebo). Participants completed a self-report measure of sex-related
      marijuana outcome expectancies at baseline and estimated likelihood of using
      condoms with a new and a steady partner in an interactive sexual role-play task
      (SRT) after smoking. In gender-specific analyses, there was a significant
      interaction of drug administration by sex-related outcome expectancies, such that
      for men in the received-placebo conditions, more salient sex-related marijuana
      outcome expectancies were associated with increased likelihood for sex without a
      condom with a new partner. Among women, there was no interaction or main effect
      of drug administration but more salient sex-related marijuana outcome
      expectancies were associated with increased likelihood of sex without a condom
      with a steady but not new partner. Findings suggest marijuana does not acutely
      increase risk for engaging in sexual risk behaviors. By contrast, sex-related
      marijuana outcome expectancies may play a more significant role in sexual
      decision-making process among marijuana users. (PsycINFO Database Record

PMID- 29048190
TI  - The efficacy and tolerability of paliperidone in mania of bipolar disorder: A
      preliminary meta-analysis.
AB  - Paliperidone may be effective for the treatment of bipolar disorder (BD);
      however, the evidence has been mixed. This is the first meta-analysis to evaluate
      the efficacy, safety, and tolerability of paliperidone for the treatment of BD.
      We performed a systematic search of the literature using major electronic
      databases from inception to January 27, 2017. Randomized control trials (RCTs)
      investigating paliperidone treatment among patients with BD versus a placebo or
      other second-generation antipsychotics were included. We then performed
      exploratory random-effects meta-analysis. The 3 included RCTs compared
      paliperidone with placebo (667 patients received paliperidone and 369 received a
      placebo). The dose of paliperidone in the included studies ranged from 3 to 12
      mg/day. Paliperidone did not significantly improve manic symptoms (Hedges' g = 
      0.221, p = .067, k = 5) compared with a placebo; however, it was superior to a
      placebo in improving psychosocial function (Hedges' g = -0.156, p = .042, k = 3)
      and general severity (Hedges' g = -0.205, p = .001, k = 5). Paliperidone was
      associated with a greater use of anticholinergic medications (p = .002),
      increased body weight (p < .001), and higher serum prolactin level (p < .001)
      compared with a placebo. Our preliminary results suggest that paliperidone does
      not offer significant benefits for the treatment of mania symptoms in BD compared
      with a placebo. In addition, treatment with paliperidone was associated with a
      higher incidence of adverse effects. Because of the limited number of studies,
      further well-designed RCTs are warranted. (PsycINFO Database Record

PMID- 29048191
TI  - Risperidone in combination with other drugs: Experimental research in individuals
      with autism spectrum disorder.
AB  - Many individuals with autism spectrum disorder simultaneously receive 2 or more
      drugs intended to improve their behavior, but few studies have evaluated the
      effects of such polypharmacy. This article summarizes those studies that have
      systematically examined the effects of risperidone, an antipsychotic drug that is
      approved by the U.S. Food and Drug Administration to treat "irritability" in
      children and adolescents with autism spectrum disorder, in combination with
      another drug with respect to experimental design, assessment techniques, drug co
      administered, reported effects, and participant characteristics. The drug
      combinations that have been evaluated do not parallel those commonly co
      administered to individuals with autism spectrum disorder in the United States,
      and there is no compelling empirical evidence to support the practice of
      prescribing risperidone in combination with another drug in an attempt to benefit
      individuals with autism spectrum disorder. (PsycINFO Database Record

PMID- 29048192
TI  - Intersectionality research in counseling psychology.
AB  - This article introduces the special section on intersectionality research in
      counseling psychology. Across the 4 manuscripts that constitute this special
      section, a clear theme emerges: a need to return to the roots and politics of
      intersectionality. Importantly, the 2 empirical articles in this special section
      (Jerald, Cole, Ward, & Avery, 2017; Lewis, Williams, Peppers, & Gadson, 2017) are
      studies of Black women's experiences: a return, so to speak, to the subject
      positions and social locations from which intersectionality emanates. Shin et al.
      (2017) explore why this focus on Black feminist thought and social justice is so
      important by highlighting the persistent weaknesses in how much research
      published in leading counseling psychology journals has tended to use
      intersectionality as a way to talk about multiple identities, rather than as a
      framework for critiquing systemic, intersecting forms of oppression and
      privilege. Shin and colleagues also point to the possibilities intersectionality
      affords us when scholars realize the transformative potential of this critical
      framework. Answers to this call for transformative practices are foregrounded in
      Moradi and Grzanka's (2017) contribution, which surveys the interdisciplinary
      literature on intersectionality and presents a series of guidelines for using
      intersectionality responsibly. We close with a discussion of issues concerning
      the applications of intersectionality to counseling psychology research that
      spans beyond the contributions of each manuscript in this special section.
      (PsycINFO Database Record

PMID- 29048193
TI  - The intersectionality framework and identity intersections in the Journal of
      Counseling Psychology and The Counseling Psychologist: A content analysis.
AB  - The framework of intersectionality is a powerful analytical tool for making sense
      of how interlocking systems of privilege and oppression are experienced by
      individuals and groups. Despite the long history of the concept,
      intersectionality has only recently gained attention in psychology. We conducted
      a content analysis to assess counseling psychology's engagement with an
      intersectional perspective. All articles published in the Journal of Counseling
      Psychology (n = 4,800) and The Counseling Psychologist (n = 1,915) from their
      first issues until July 2016 were reviewed to identify conceptual and empirical
      work focused on intersectionality. A total of 40 articles were identified and
      examined for themes. Limitations and future directions are discussed. (PsycINFO
      Database Record

PMID- 29048194
TI  - Applying intersectionality to explore the relations between gendered racism and
      health among Black women.
AB  - The purpose of this study was to apply an intersectionality framework to explore
      the influence of gendered racism (i.e., intersection of racism and sexism) on
      health outcomes. Specifically, we applied intersectionality to extend a
      biopsychosocial model of racism to highlight the psychosocial variables that
      mediate and moderate the influence of gendered racial microaggressions (i.e.,
      subtle gendered racism) on health outcomes. In addition, we tested aspects of
      this conceptual model by exploring the influence of gendered racial
      microaggressions on the mental and physical health of Black women. In addition,
      we explored the mediating role of coping strategies and the moderating role of
      gendered racial identity centrality. Participants were 231 Black women who
      completed an online survey. Results from regression analyses indicated that
      gendered racial microaggressions significantly predicted both self-reported
      mental and physical health outcomes. In addition, results from mediation analyses
      indicated that disengagement coping significantly mediated the link between
      gendered racial microaggressions and negative mental and physical health. In
      addition, a moderated mediation effect was found, such that individuals who
      reported a greater frequency of gendered racial microaggressions and reported
      lower levels of gendered racial identity centrality tended to use greater
      disengagement coping, which in turn, was negatively associated with mental and
      physical health outcomes. Findings of this study suggest that gendered racial
      identity centrality can serve a buffering role against the negative mental and
      physical health effects of gendered racism for Black women. (PsycINFO Database
      Record

PMID- 29048195
TI  - Controlling images: How awareness of group stereotypes affects Black women's well
      being.
AB  - This paper presents research exploring how stereotypes that are simultaneously
      racialized and gendered affect Black women. We investigated the mental and
      physical health consequences of Black women's awareness that others hold these
      stereotypes and tested whether this association was moderated by the centrality
      of racial identity. A structural equation model tested among 609 young Black
      women revealed that metastereotype awareness (i.e., being aware that others hold
      negative stereotypes of one's group) predicted negative mental health outcomes
      (e.g., depression, anxiety, hostility), which, in turn, predicted diminished self
      care behaviors and greater drug and alcohol use for coping. High racial
      centrality exacerbated the negative association between metastereotype awareness
      and self-care. We discuss implications of the findings for clinical practice and
      for approaches to research using intersectionality frameworks. (PsycINFO Database
      Record

PMID- 29048196
TI  - Using intersectionality responsibly: Toward critical epistemology, structural
      analysis, and social justice activism.
AB  - The increasing popularity of the concept of intersectionality in the social
      sciences, including in psychology, represents an opportunity to reflect on the
      state of stewardship of this concept, its roots, and its promise. In this
      context, the authors aim to promote responsible stewardship of intersectionality
      and to tip the momentum of intersectionality's flourishing toward fuller use and
      engagement of its roots and promise for understanding and challenging dynamics of
      power, privilege, and oppression. To this end, this article provides a set of
      guidelines for reflection and action. The authors organize these guidelines along
      3 major formulations of intersectionality: intersectionality as a field of study,
      as analytic strategy or disposition, and as critical praxis for social justice.
      Ultimately, the authors call for expanding the use of intersectionality toward
      fuller engagement with its roots in Black feminist thought, its current
      interdisciplinary richness and potential, and its central aims to challenge and
      transform structures and systems of power, privilege, and oppression. (PsycINFO
      Database Record

PMID- 29048197
TI  - A longitudinal investigation of the impact of psychotherapist training: Does
      training improve client outcomes?
AB  - This study is a longitudinal examination of the impact of therapist stage of
      training on client outcomes in psychotherapy. The study included 22 PhD-level
      psychologists who work in a university counseling center (8 female, 14 male) who
      had completed at least 2 training periods in the center where data were gathered.
      Therapists worked with 4,047 clients, and 40,271 sessions were included in our
      analyses. Clients were given the Outcome Questionnaire-45 (OQ-45) on a session-by
      session basis, tracking treatment response. The effect of stage of training on
      both the magnitude and speed of OQ-45 change was examined through hierarchical
      linear modeling. Therapists were found to achieve the same amount of change or
      less change on average in their later stages of training. Therapists were also
      found, on average, to achieve the same rate of change or a slower rate of change
      in later stages of training. Findings suggest that as therapists progress through
      formal stages of training, they do not improve in their ability to effect change
      in their clients. Given these findings, a better understanding of expertise in
      psychotherapy practice and how to develop it may be an important area for future
      theory development, research, and training program development. We call for
      further work examining if and how an individual therapist can become more
      effective with time. (PsycINFO Database Record

PMID- 29048198
TI  - Autonomous and controlled motivation for interpersonal therapy for depression:
      Between-therapists and within-therapist effects.
AB  - Differences between therapists in the average outcomes their patients achieve are
      well documented, and researchers have begun to try to explain such differences
      (Baldwin & Imel, 2013). Guided by Self-Determination Theory (Deci & Ryan, 2000),
      we examined the effects on outcome of differences between therapists in their
      patients' average levels of autonomous and controlled motivation for treatment,
      as well as the effects of differences among the patients within each therapist's
      caseload. Between and within-therapist differences in the SDT construct of
      perceived relational support were explored as predictors of patients' motivation.
      Nineteen therapists treated 63 patients in an outpatient clinic providing
      manualized interpersonal therapy (IPT) for depression. Patients completed the BDI
      II at pretreatment, posttreatment, and each treatment session. The Impact Message
      Inventory was administered at the third session and scored for perceived
      therapist friendliness, a core element of relational support. We created between
      therapists (therapist-level) scores by averaging over the patients in each
      therapist's caseload; within-therapist (patient-level) scores were computed by
      centering within each therapist's caseload. As expected, better outcome was
      predicted by higher levels of therapist-level and patient-level autonomous
      motivation and by lower levels of therapist-level and patient-level controlled
      motivation. In turn, autonomous motivation was predicted by therapist-level and
      patient-level relational support (friendliness). Controlled motivation was
      predicted solely by patient self-critical perfectionism. The results extend past
      work by demonstrating that both between-therapists and within-therapist
      differences in motivation predict outcome. As well, the results suggest that
      therapists should monitor their interpersonal impact so as to provide relational
      support. (PsycINFO Database Record

PMID- 29048199
TI  - Polyamine-Based Thiols in Trypanosomatids: Evolution, Protein Structural
      Adaptations, and Biological Functions.
AB  - SIGNIFICANCE: Major pathogenic enterobacteria and protozoan parasites from the
      phylum Euglenozoa, such as trypanosomatids, are endowed with glutathione (GSH)
      spermidine (Sp) derivatives that play important roles in signaling and metal and
      thiol-redox homeostasis. For some Euglenozoa lineages, the GSH-Sp conjugates
      represent the main redox cosubstrates around which entire new redox systems have
      evolved. Several proteins underwent molecular adaptations to synthesize and
      utilize the new polyamine-based thiols. Recent Advances: The genomes of closely
      related organisms have recently been sequenced, which allows mining and analysis
      of gene sequences that belong to these peculiar redox systems. Similarly, the
      three-dimensional structures of several of these proteins have been solved, which
      allows for comparison with their counterparts in classical redox systems that
      rely on GSH/glutaredoxin and thioredoxin. CRITICAL ISSUES: The evolutionary and
      structural aspects related to the emergence and use of GSH-Sp conjugates in
      Euglenozoa are reviewed focusing on unique structural specializations that
      proteins developed to use N1,N8-bisglutathionylspermidine (trypanothione) as
      redox cosubstrate. An updated overview on the biochemical and biological
      significance of the major enzymatic activities is also provided. FUTURE
      DIRECTIONS: A thiol-redox system strictly dependent on trypanothione is a feature
      unique to trypanosomatids. The physicochemical properties of the polyamine-GSH
      conjugates were a major driving force for structural adaptation of proteins that
      use these thiols as ligand and redox cofactor. In fact, the structural
      differences of indispensable components of this system can be exploited toward
      selective drug development. Future research should clarify whether additional
      cellular processes are regulated by the trypanothione system. Antioxid. Redox
      Signal. 28, 463-486.

PMID- 29048201
TI  - Hygienic Shortcomings of Frozen Dessert Freezing Equipment and Fate of Listeria
      monocytogenes on Ice Cream-Soiled Stainless Steel.
AB  - Although frozen dairy desserts have a strong record of safety, recent outbreaks
      of foodborne disease linked to ice creams have brought new attention to this
      industry. There is concern that small-scale frozen dessert equipment may not
      comply with or be reviewed against published comprehensive design and
      construction sanitation specifications (National Sanitation Foundation or 3-A
      sanitary standards). Equipment sanitary design issues may result in reduced
      efficacy of cleaning and sanitation, thus increasing the likelihood of
      postprocess contamination with pathogenic bacteria. In this context, and given
      that Listeria monocytogenes outbreaks are of great concern for the frozen dessert
      industry, a complementary study was conducted to evaluate the fate of L.
      monocytogenes in ice cream mix on a stainless steel surface. Our results showed
      that L. monocytogenes survived for up to 6 weeks at room temperature and 9 weeks
      at 4 degrees C in contaminated ice cream on a stainless steel surface.
      Furthermore, chlorine- and acid-based surface sanitizers had no detrimental
      effect on the L. monocytogenes when used at a concentration and contact time (1
      min) recommended by the manufacturer; significant reduction in CFU required 5 to
      20 min of contact time.

PMID- 29048200
TI  - Automated Quantification of the Landing Error Scoring System With a Markerless
      Motion-Capture System.
AB  - CONTEXT:   The Landing Error Scoring System (LESS) can be used to identify
      individuals with an elevated risk of lower extremity injury. The limitation of
      the LESS is that raters identify movement errors from video replay, which is time
      consuming and, therefore, may limit its use by clinicians. A markerless motion
      capture system may be capable of automating LESS scoring, thereby removing this
      obstacle. OBJECTIVE:   To determine the reliability of an automated markerless
      motion-capture system for scoring the LESS. DESIGN:   Cross-sectional study.
      SETTING:   United States Military Academy. PATIENTS OR OTHER PARTICIPANTS:   A
      total of 57 healthy, physically active individuals (47 men, 10 women; age = 18.6
      +/- 0.6 years, height = 174.5 +/- 6.7 cm, mass = 75.9 +/- 9.2 kg). MAIN OUTCOME
      MEASURE(S):   Participants completed 3 jump-landing trials that were recorded by
      standard video cameras and a depth camera. Their movement quality was evaluated
      by expert LESS raters (standard video recording) using the LESS rubric and by
      software that automates LESS scoring (depth-camera data). We recorded an error
      for a LESS item if it was present on at least 2 of 3 jump-landing trials. We
      calculated kappa statistics, prevalence- and bias-adjusted kappa (PABAK)
      statistics, and percentage agreement for each LESS item. Interrater reliability
      was evaluated between the 2 expert rater scores and between a consensus expert
      score and the markerless motion-capture system score. RESULTS:   We observed
      reliability between the 2 expert LESS raters (average kappa = 0.45 +/- 0.35,
      average PABAK = 0.67 +/- 0.34; percentage agreement = 0.83 +/- 0.17). The
      markerless motion-capture system had similar reliability with consensus expert
      scores (average kappa = 0.48 +/- 0.40, average PABAK = 0.71 +/- 0.27; percentage
      agreement = 0.85 +/- 0.14). However, reliability was poor for 5 LESS items in
      both LESS score comparisons. CONCLUSIONS:   A markerless motion-capture system
      had the same level of reliability as expert LESS raters, suggesting that an
      automated system can accurately assess movement. Therefore, clinicians can use
      the markerless motion-capture system to reliably score the LESS without being
      limited by the time requirements of manual LESS scoring.

PMID- 29048202
TI  - Editorial Comment on: Comparison of Perioperative Outcomes Between Holmium Laser
      Enucleation of the Prostate and Robot-Assisted Simple Prostatectomy by Zhang et
      al. (From: Zhang MW, El Tayeb MM, Borofsky MS, et al. J Endourol 2017;31:847
      850).

PMID- 29048203
TI  - Editorial Comment on: An Innovative Technique of Transurethral Seminal
      Vesiculoscopy with Ultrasonic Lithotripter for Severe, Persistent Hematospermia
      by Zhang et al.

PMID- 29048204
TI  - Editorial Comment on: Defining the Costs of Reusable Flexible Ureteroscope
      Reprocessing Using Time-Driven Activity Based Costing by Isaacson et al. (From:
      Isaacson D, Ahmad T, Metzler, I, et al. J Endourol 2017;31:1026-1031).

PMID- 29048205
TI  - Cardiac rehabilitation after percutaneous coronary intervention: Results from a
      nationwide survey.
AB  - AIM: The purpose of this study was to estimate the proportion of Norwegian
      coronary heart disease patients participating in cardiac rehabilitation
      programmes after percutaneous coronary intervention, and to determine predictors
      of cardiac rehabilitation participation. METHODS: Participants were patients
      enrolled in the Norwegian Coronary Stent Trial. We assessed cardiac
      rehabilitation participation in 9013 of these patients who had undergone their
      first percutaneous coronary intervention during 2008-2011. Of these, 7068
      patients (82%) completed a self-administered questionnaire on cardiac
      rehabilitation participation within three years after their percutaneous coronary
      intervention. RESULTS: Twenty-eight per cent of the participants reported
      engaging in cardiac rehabilitation. Participation rate differed among the four
      regional health authorities in Norway, varying from 20%-31%. Patients undergoing
      percutaneous coronary intervention for an acute coronary syndrome were more
      likely to participate in cardiac rehabilitation than patients with stable angina
      (odds ratio 3.2; 95% confidence interval 2.74-3.76). A multivariate statistical
      model revealed that men had a 28% lower probability ( p<0.001) of participating
      in cardiac rehabilitation, and the odds of attending cardiac rehabilitation
      decreased with increasing age ( p<0.001). Contributors to higher odds of cardiac
      rehabilitation participation were educational level >12 years (odds ratio 1.50;
      95% confidence interval 1.32-1.71) and body mass index>25 (odds ratio 1.19; 95%
      confidence interval 1.05-1.36). Prior coronary artery bypass graft was associated
      with lower odds of cardiac rehabilitation participation (odds ratio 0.47; 95%
      confidence interval 0.32-0.70) Conclusion: The estimated cardiac rehabilitation
      participation rate among patients undergoing first-time percutaneous coronary
      intervention is low in Norway. The typical participant is young, overweight, well
      educated, and had an acute coronary event. These results varied by geographical
      region.

PMID- 29048206
TI  - Analysis of the Efficacy and Safety of Increasing the Energy Dose Applied Per
      Session by Increasing the Number of Shock Waves in Extracorporeal Lithotripsy: A
      Prospective and Comparative Study.
AB  - PURPOSE: To evaluate the efficacy and safety of increasing the energy dose in
      treating urinary lithiasis with extracorporeal lithotripsy through an expanded
      number of Shock Waves Per Session (SWPS). MATERIALS AND METHODS: a randomized,
      prospective, and comparative study was performed with patients with renal or
      ureteral lithiasis from 2011 to 2014. Two groups were studied: Group A (n = 136),
      treated with 3500 SWPS, and Group B (n = 171), subjected to an expanded treatment
      with 7000 SWPS. Patients were considered stone free when there was no lithiasis
      or it were less or equal to 4 mm after treatment. Variables related to the
      patient, stones, treatment, and complications were collected. RESULTS: The global
      SFR was 75.0% and 87.7% in Groups A and B, respectively (p = 0.004). In renal
      location, the SFR was higher in Group B (74.1% vs 90.7%, p = 0.003) regardless of
      the size. In the ureteral location, there were differences in the pelvic only
      (73.7% vs 95.2%). There were no differences in either the complication rate
      (27.2% vs 25.7%, p = 0.77), or the severity between the two groups. The variable
      "number of SWPS" was seen to be an independent predictor of the resolution of
      lithiasis, having the probability of resolving lithiasis 2.62 (CI 95% = 1.40
      4.89) times greater when applying 7000 SWPS. CONCLUSION: In our study, increasing
      the energy dose applied through an expanded number of SWPS has been shown to be
      more effective than standard regimens with a similar safety profile. However,
      more clinical studies on different types of lithotripters are required to confirm
      these results.

PMID- 29048207
TI  - Acute inflammation and long-term cardiovascular risk: Identifying an unrecognised
      vulnerable gap.

PMID- 29048208
TI  - An Innovative Technique of Transurethral Seminal Vesiculoscopy with Ultrasonic
      Lithotripter for Severe, Persistent Hematospermia.
AB  - BACKGROUND AND PURPOSE: Transurethral seminal vesiculoscopy (TSV) provides an
      efficient approach to diagnose and treat hematospermia, but still needs further
      improvement in manipulation and corresponding instruments. In this study, we
      develop an innovative technique with ultrasonic lithotripter (EMS) to treat
      severe, persistent hematospermia. PATIENTS AND METHODS: Data of patients who
      underwent TSV with or without ultrasonic lithotripter between May 2012 and
      December 2015 was reviewed. For the innovative procedure, a 3.3F ultrasonic
      lithotripter was introduced through the working channel of an 8F seminal
      vesiculoscope to remove calculi, blood clots, or purulent material, whereas in
      routine procedure, the holmium laser lithotripsy was performed with lower energy
      (maximum power 10 W). Complication, hematospermia recurrence, the operative time,
      and postoperative hospitalization were recorded. RESULTS: A total of 30 patients,
      16 in Group A (routine TSV) and 14 in Group B (TSV with ultrasonic lithotripter
      procedure), were involved in this study. The median follow-up time for patients
      in Group A and B was 28 and 31 months, respectively. The mean operative time in
      Group A and B was 66 and 50 minutes, respectively (p < 0.05). All the TSV
      procedures in Group B were successful, except one patient had a two-stage
      procedure because of right seminal vesicle stones accompanying with pus. One
      patient in Group A had the discontinuation of the procedure because of accidental
      bleeding during stone fragmentation. During the follow-up, two patients in Group
      A had recurrent hematospermia and underwent the second TSV, whereas no recurrence
      happened in Group B. No epididymitis, retrograde ejaculation, rectal injury,
      incontinence, bladder neck contracture, or erectile dysfunction happened in both
      groups. CONCLUSION: TSV with ultrasonic lithotripter enables a more reliable,
      effective, and convenient procedure to diagnose and treat severe, persistent
      hematospermia. It controls the recurrent hematospermia with less operative time
      and complication.

PMID- 29048209
TI  - Percuflex Helical Ureteral Stents Significantly Reduce Patient Analgesic
      Requirements Compared to Control Stents.
AB  - INTRODUCTION AND OBJECTIVES: Ureteral stent symptoms are experienced by the
      majority of patients with ureteral stents. No one stent or technology has shown a
      clear advantage. The HelicalTM stent, a spirally cut stent made of proprietary
      PercuflexTM material, was designed to conform to the shape of the ureter and
      better accommodate patient movement. We prospectively sought to compare
      unscheduled visits, analgesic use, and pain scores in patients who received a
      Percuflex Helical ureteral stent following ureteroscopy compared to a historical
      control group. METHODS: Fifteen (n = 15) patients undergoing ureteroscopy for the
      treatment of kidney stones were consented for study. A Percuflex Helical ureteral
      stent was inserted after treating the urinary stone. The historical control group
      consisted of 30 patients, from a previous (ketorolac eluting) ureteral stent
      study utilizing the same protocol and clinical monitoring forms, who received a
      regular Percuflex ureteral stent. The control patients were matched by age and
      sex. The primary study outcome was to compare unscheduled visits. Secondary
      outcomes included comparison of Visual Pain Analog Scale (VPAS) scores and
      analgesic use between the two groups. RESULTS: There were no differences in the
      gender, age, BMI, or stone characteristics between groups. Both groups underwent
      retrograde ureteroscopy using holmium:YAG laser lithotripsy and stone
      fragmentation. There was a significant reduction in the amount of analgesics
      required in the Helical stent group (4.4 +/- 7.99 mg morphine equivalents)
      compared to controls (16.75 +/- 18.31 mg, p = 0.0035) to achieve similar VPAS
      scores. There was no difference in unscheduled visits (20%) or VPAS scores (13.84
      +/- 13.68 helical vs 14.29 +/- 11.58 control, p = 0.7910) between groups.
      CONCLUSIONS: Patients who received a Percuflex Helical ureteral stent required
      significantly fewer analgesics than those who received a Percuflex stent and both
      had equivalent pain scores.

PMID- 29048212
TI  - Living Too Long? Exploring Attitudes Toward Reaching 100 Years Old.
AB  - Objective This study analyses the relationship between pro- and anti-longevity
      attitudes, attitudes toward centenarians, and the wish to reach 100 years of age
      in a sample of community dwelling older adults. Methods Participants ( N = 137)
      completed a questionnaire on attitudes toward life-extension and an aging
      semantic differential using centenarians as an attitudinal target.
      Sociodemographic information, perceived health status, and information on knowing
      a centenarian were also obtained. A cluster analysis was used to identify
      subgroups (leaning anti-longevity group vs. leaning prolongevity group), and
      their associations with personal attributes were tested using logistic regression
      models. Results Most respondents said they would wish to reach 100 years old
      (54.7%) and presented a leaning positive attitude toward centenarians (52.6%).
      Holding a negative attitude toward centenarians rather than any other attribute
      increases the odds of having more negative attitudes toward life extension.
      Conclusion Results stress the importance of social views on extreme longevity in
      shaping life extension attitudes.

PMID- 29048211
TI  - Ureteroscopy in Patients with Bleeding Diatheses, Anticoagulated, and on Anti
      Platelet Agents: A Systematic Review and Meta-Analysis of the Literature.
AB  - INTRODUCTION: Ureteroscopy (URS) is the most common surgical treatment of
      urolithiasis and can be problematic in patients with a bleeding diathesis. The
      intent of this review is to systematically review the literature to assess the
      safety and efficacy of ureteroscopic procedures in these groups of patients.
      METHODS: The systematic review was performed according to the Cochrane diagnostic
      accuracy review guidelines. The search strategy was conducted to perform a
      comprehensive database search (1990-2017). A cumulative analysis was done and
      where applicable a comparative analysis between bleeding diathesis patients and
      those without. RESULTS: Eight studies included were all published between 1998
      and 2016 with the total number of participants with bleeding diatheses being 1109
      with an age range of 18-97. Overall stone-free rate across the studies was 90.8%
      vs 86.2% in the control group. There was no significant difference in
      complications between the bleeding diathesis group and control group (N = 12,757,
      p = 0.07, 95% confidence interval [CI] 0.92, 6.02, I2 = 78%). Pooled analysis for
      bleeding-related complications shows a statistically significant difference
      favoring the control arm (N = 12,757, p <= 0.0001, 95% CI 1.81, 5.73, I2 = 0%).
      Pooled analysis for thrombosis shows no statistically significant difference
      between the bleeding diathesis group and the control arm (N = 118, p = 0.67, 95%
      CI 0.23, 9.86, I2 = 48%). CONCLUSION: The use of URS with or without the holmium
      laser is a safe and efficient modality for treating patients with urolithiasis
      who also have a bleeding diathesis or are anticoagulated or on antiplatelet
      agents. However, this review would suggest that the increased risk of procedure
      related bleeding is not insignificant and a patient-centered approach should be
      taken with regards to continuing these agents or not correcting bleeding
      diatheses.

PMID- 29048213
TI  - Structural Modeling the Relationship of Food Addiction and Eating Attitudes of
      Young Adults with Emotional Appetite and Self-Esteem.
AB  - The aim of the study was to examine the relationships among food addiction,
      eating attitudes, emotional appetite, and self-esteem of young adults aged 18-30
      years by using a structural model. This cross-sectional study was conducted with
      1,058 volunteers (male = 307, female = 751). The hypothesis that self-esteem of
      young adults influences their eating attitudes was supported in the study (beta =
      -0.081, p < .05). Another hypothesis was also supported, so self-esteem had a
      positive effect on food addiction (beta = 0.280, p < .05). Furthermore, eating
      attitude has mediating effects on the relationships between self-esteem and food
      addiction and between emotional appetite and food addiction. Individuals' eating
      attitude, food addiction, emotional appetite, and self-esteem scores were found
      to be related to each other. This article provides valuable data for studies of
      disordered eating attitudes, emotional state, and food addiction that are thought
      to be important for young adults in the future.

PMID- 29048214
TI  - Validation of a Full-Immersion Simulation Platform for Percutaneous
      Nephrolithotomy Using Three-Dimensional Printing Technology.
AB  - INTRODUCTION AND OBJECTIVES: The restriction of resident hours with an increasing
      focus on patient safety and a reduced caseload has impacted surgical training. A
      complex and complication prone procedure such as percutaneous nephrolithotomy
      (PCNL) with a steep learning curve may create an unsafe environment for hands-on
      resident training. In this study, we validate a high fidelity, inanimate PCNL
      model within a full-immersion simulation environment. METHODS: Anatomically
      correct models of the human pelvicaliceal system, kidney, and relevant adjacent
      structures were created using polyvinyl alcohol hydrogels and three-dimensional
      printed injection molds. All steps of a PCNL were simulated including
      percutaneous renal access, nephroscopy, and lithotripsy. Five experts (>100
      caseload) and 10 novices (<20 caseload) from both urology (full procedure) and
      interventional radiology (access only) departments completed the simulation. Face
      and content validity were calculated using model ratings for similarity to the
      real procedure and usefulness as a training tool. Differences in performance
      among groups with various levels of experience using clinically relevant
      procedural metrics were used to calculate construct validity. RESULTS: The model
      was determined to have an excellent face and content validity with an average
      score of 4.5/5.0 and 4.6/5.0, respectively. There were significant differences
      between novice and expert operative metrics including mean fluoroscopy time, the
      number of percutaneous access attempts, and number of times the needle was
      repositioned. Experts achieved better stone clearance with fewer procedural
      complications. CONCLUSIONS: We demonstrated the face, content, and construct
      validity of an inanimate, full task trainer for PCNL. Construct validity between
      experts and novices was demonstrated using incorporated procedural metrics, which
      permitted the accurate assessment of performance. While hands-on training under
      supervision remains an integral part of any residency, this full-immersion
      simulation provides a comprehensive tool for surgical skills development and
      evaluation before hands-on exposure.

PMID- 29048215
TI  - Sauna exposure leads to improved arterial compliance: Findings from a non
      randomised experimental study.
AB  - Background Heat therapy has been suggested to improve cardiovascular function.
      However, the effects of hot sauna exposure on arterial compliance and the
      dynamics of blood flow and pressure have not been well documented. Thus, we
      investigated the short-term effects of sauna bathing on arterial stiffness and
      haemodynamics. Design The design was an experimental non-randomised study.
      Methods There were 102 asymptomatic participants (mean age, 51.9 years) who had
      at least one cardiovascular risk factor. Participants were exposed to a single
      sauna session (duration: 30 min; temperature: 73C; humidity: 10-20%). Pulse wave
      velocity, augmentation index, heart rate, blood pressure, mean arterial pressure,
      pulse pressure, augmented pressure and left ventricular ejection time were
      assessed before, immediately after, and 30 min after a single sauna session.
      Results Sauna bathing led to reductions in pulse wave velocity, blood pressure,
      mean arterial pressure and left ventricular ejection time. Mean pulse wave
      velocity value before sauna was 9.8 m/s and decreased to 8.6 m/s immediately
      after sauna bathing ( p < 0.001 for difference), and was 9.0 m/s after the 30
      minute recovery period ( p < 0.001 for analysis of variance). Systolic blood
      pressure was 137 mm Hg before sauna bathing, decreasing to 130 mm Hg after sauna
      ( p < 0.001), which remained sustained during the 30-minute recovery phase ( p <
      0.001 for analysis of variance). After a single sauna session, diastolic blood
      pressure decreased from 82 to 75 mm Hg, mean arterial pressure from 99.4 to 93.6
      mm Hg and left ventricular ejection time from 307 to 278 m/s ( p < 0.001 for all
      differences). Pulse pressure was 42.7 mm Hg before the sauna, 44.9 mm Hg
      immediately after the sauna, and reduced to 39.3 mm Hg after 30-minutes recovery
      ( p < 0.001 for analysis of variance). Heart rate increased from 65 to 81
      beats/min post-sauna ( p < 0.001); there were no significant changes for
      augmented pressure and pulse pressure amplification. Conclusion This study shows
      that pulse wave velocity, systolic blood pressure, diastolic blood pressure, mean
      arterial pressure, left ventricular ejection time and diastolic time decreased
      immediately after a 30-minute sauna session. Decreases in systolic blood pressure
      and left ventricular ejection time were sustained during the 30-minute recovery
      phase.

PMID- 29048210
TI  - Breastfeeding Challenges and the Preterm Mother-Infant Dyad: A Conceptual Model.
AB  - Breastfeeding is an experience that only a mother and her infant(s) can share.
      Infants who can feed from the breast receive not only the best nutrition but
      also, due to the close physical contact between mother and child, it is the
      optimal nurturance they can receive from their mother. When breastfeeding is
      trouble free, maternal well-being is uniquely heightened. However, breastfeeding
      remains a challenge for many mother-infant dyads and more so for those whose
      infants are born prematurely. This article introduces a conceptual model of the
      breastfeeding challenges facing preterm mother-infant dyads. It distinguishes
      between a maternal caregiving and an infant growth/development components. Within
      the maternal component, two primary elements are considered, that is, maternal
      behavioral and nutritional care. The two primary elements within the infant
      component include infant non-nutritional and nutritional growth/development. It
      is proposed that an improved understanding of the factors associated with these
      four elements and how they interplay with each other within individual dyads will
      facilitate the identification of the breastfeeding challenges facing these mother
      infant entities. Due to the intimate relationships existing between a mother and
      her infant(s), it is further advanced that breastfeeding studies would be
      optimized if mother-infant pairs are studied as one entity rather than mother and
      infant separately. It is proposed that this conceptual model will assist health
      professionals develop personalized breastfeeding management plans for individual
      preterm mother-infant dyads, while furthering the development of evidence-based
      interventions to optimize their breastfeeding experiences.

PMID- 29048216
TI  - Thermal Response to High-Power Holmium Laser Lithotripsy.
AB  - OBJECTIVES: The aim of this study was to investigate "caliceal" fluid temperature
      changes during holmium laser activation/lithotripsy using settings up to 40 W
      power output with different irrigation flow rates. MATERIALS AND METHODS: The
      experimental system consisted of a glass test tube (diameter 10 mm/length 75 mm)
      filled with deionized water, to mimic a calix. Real-time temperature was recorded
      using a thermocouple (Physitemp, NJ) positioned 5 mm from the bottom of the tube.
      A 200 MUm laser fiber (Flexiva; Boston Scientific, MA) was introduced through the
      working channel of a disposable ureteroscope (LithoVue; Boston Scientific) and
      the laser fiber tip was positioned 15 mm above the bottom of the test tube.
      Deionized water irrigation (room temperature) through the working channel of the
      ureteroscope was delivered at flow rates of 0, 7-8, 14-15, and 38-40 mL/minute. A
      120-W holmium laser (pulse 120; Lumenis, CA) was used. The following settings
      were explored: 0.5 J * 10 Hz, 1.0 J * 10 Hz, 0.5 J * 20 Hz, 1.0 J * 20 Hz, 0.5 J
      * 40 Hz, 1.0 J * 40 Hz, and 0.5 J * 80 Hz. During each experiment, the laser was
      activated continuously for 60 seconds. RESULTS: Temperature increased with
      increasing laser power output and decreasing irrigation flow rate. The highest
      temperature, 70.3 degrees C (standard deviation 2.7), occurred with laser setting
      of 1.0 J * 40 Hz and no irrigation after 60 seconds of continuous laser firing.
      None of the tested laser settings and irrigation parameters produced temperature
      exceeding 51 degrees C when activated for only 10 seconds of continuous laser
      firing. CONCLUSION: High-power holmium settings fired in long bursts with low
      irrigation flow rates can generate high fluid temperatures in a laboratory
      "caliceal" model. Awareness of this risk allows urologist to implement a variety
      of techniques (higher irrigation flow rates, intermittent laser activation, and
      potentially cooled irrigation fluid) to control and mitigate thermal effects
      during holmium laser lithotripsy.

PMID- 29048217
TI  - Electrocardiographic unrecognized myocardial infarction does not improve
      prediction of cardiovascular events beyond traditional risk factors. The Tromso
      Study.
AB  - Background Unrecognized myocardial infarction (MI) is a frequent and intriguing
      entity associated with a similar risk of death as recognized MI. Previous studies
      have not fully addressed whether the poor prognosis is explained by traditional
      cardiovascular risk factors. We investigated whether electrocardiographically
      detected unrecognized MI was independently associated with cardiovascular events
      and death and whether it improved prediction for future MI in a general
      population. Design Prospective cohort study. Methods We studied 5686 women and
      men without clinically recognized MI at baseline in 2007-2008. We assessed the
      risk of future MI, stroke and all-cause mortality in persons with unrecognized MI
      compared with persons with no MI during 31,051 person-years of follow-up. Results
      In the unadjusted analyses, unrecognized MI was associated with increased risk of
      future recognized MI (hazard ratio 1.84, 95% confidence interval (CI) 1.15-2.96)
      and all-cause mortality (hazard ratio 1.78, 95% CI 1.21-2.61), but not stroke
      (hazard ratio 1.09, 95% CI 0.56-2.17). The associations did not remain
      significant after adjustment for traditional risk factors (hazard ratio 1.25, 95%
      CI 0.76-2.06 and hazard ratio 1.38, 95% CI 0.93-2.05) for MI and all-cause
      mortality respectively. Unrecognized MI did not improve risk prediction for
      future recognized MI using the Framingham Risk Score ( p = 0.96) or the European
      Systematic COronary Risk Evaluation ( p = 0.65). There was no significant sex
      interaction regarding any of the endpoints. Conclusion Electrocardiographic
      unrecognized MI was not significantly associated with future risk of MI, stroke
      or all-cause mortality in the general population after adjustment for the
      traditional cardiovascular risk factors, and it did not improve prediction of
      future MI.

PMID- 29048218
TI  - Radiotherapy for Patients With Resected Tumor Deposit-Positive Colorectal Cancer:
      A Surveillance, Epidemiology, and End Results-Based Population Study.
AB  - CONTEXT: - According to the American Joint Committee on Cancer's Cancer Staging
      Manual, 7th edition, TNM classification, tumor deposit (TD)-positive colorectal
      cancers (CRCs) are classified as N1c. The effects of radiotherapy and the effects
      of the updated American Joint Committee on Cancer 7th edition TNM N1c
      classification for patients with TD-positive CRC are unclear. OBJECTIVE: - To
      investigate outcomes of radiotherapy in patients with resected TD-positive CRC.
      DESIGN: - Resected TD-positive CRCs diagnosed from 2010 to 2014 were identified
      in the Surveillance, Epidemiology, and End Results 18 database. Factors
      associated with overall survival (OS) and cancer-specific survival (CSS) were
      investigated using Kaplan-Meier and Cox proportional hazards models. RESULTS: -
      We included 2712 qualified CRC patients, who either underwent adjuvant
      radiotherapy (n = 187; 6.9%) or received no radiotherapy (n = 2525; 93.1%).
      Univariate Cox proportional models showed improved CSS among all CRC patients who
      underwent adjuvant radiotherapy (CSS hazard ratio, 0.73; 95% CI, 0.57-0.95) and
      among rectal cancer patients when separated by location (hazard ratio, 0.57; 95%
      CI, 0.40-0.83), although these associations were attenuated in multivariable
      adjusted models. There was improved OS among rectal cancer patients (hazard
      ratio, 0.77; 95% CI, 0.59-0.99). In subgroup analyses, radiotherapy was not
      associated with OS or CSS in either metastatic or nonmetastatic CRC patients.
      Instead, N1c category (versus N0) was associated with a worse OS (hazard ratio,
      1.43; 95% CI, 1.31-1.57) but was not associated with CSS. CONCLUSIONS: -
      Radiotherapy did not independently improve OS among TD-positive CRC patients. In
      this study, classifying TD positivity as N1c was associated with worse OS than
      classifying TD positivity as N0. The findings seem to challenge the benefits of
      radiotherapy and the new N1c classification of TD for TD-positive CRC patients.

PMID- 29048219
TI  - Immunohistochemistry in Peritoneal Mesothelioma: A Single-Center Experience of
      244 Cases.
AB  - CONTEXT: - Diagnosis of malignant mesothelioma is more common in the chest than
      it is in the abdomen. Most published immunohistochemistry data are more
      applicable to pleural than to peritoneal mesothelioma. OBJECTIVE: - To clarify
      the practical utility of 17 immunohistochemistry markers in the differential
      diagnosis of peritoneal mesothelioma with an emphasis on stains for which there
      is either contradictory information or a paucity of literature. DESIGN: -
      Consultation files of peritoneal mesothelioma diagnoses rendered from 1999 to
      2014 were reviewed; 244 cases were identified. The results of
      immunohistochemistry markers performed were tabulated. RESULTS: -
      Immunohistochemistry markers positive in peritoneal mesothelioma in order of
      sensitivity were calretinin (244 of 244; 100%), WT1 (205 of 218; 94%), CK5/6 (173
      of 194; 89%), mesothelin (132 of 150; 88%), and D2-40 (78 of 97; 80%). Markers
      used to differentiate carcinoma from mesothelioma showed immunoreactivity in
      peritoneal mesothelioma: estrogen receptor (2 of 84; 2%), B72.3 (6 of 196; 3%),
      CK20 (5 of 116; 4%), CD15 (7 of 192; 4%), p63 (3 of 62; 5%), carcinoembryonic
      antigen (9 of 199; 5%), PAX8 (12 of 191; 6%), progesterone receptor (5 of 71;
      7%), Ber-EP4 (17 of 209; 8%), and CD138 (9 of 91; 10%). BAP1 loss, increasingly
      used in the differential diagnosis of benign versus malignant mesothelial
      proliferation, occured in 55% (99 of 181) of peritoneal mesothelioma cases.
      CONCLUSIONS: - The results support the experience that there is no definitive
      marker to rule out malignant mesothelioma, including PAX8, estrogen receptor,
      progesterone receptor, and p63 immunoreactivity. The high rate of
      immunoreactivity for mesothelin may have a role as a predictive marker for immune
      targeting. BAP1 loss of 55% in this cohort of peritoneal mesothelioma confirms
      published observations, and BAP1 retention is seen in a significant proportion of
      neoplastic cases.

PMID- 29048220
TI  - Performance Characteristics of Body Fluid Cytology Analysis of 344 380 Responses
      From the College of American Pathologists Interlaboratory Comparison Program in
      Nongynecologic Cytopathology.
AB  - CONTEXT: - Body fluid cytology is an important diagnostic tool used to identify
      various conditions. However, an accurate diagnosis in this setting can sometimes
      be challenging. OBJECTIVE: - To identify the performance characteristics of body
      fluid cytology by analyzing participant responses from the College of American
      Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology.
      DESIGN: - Participant responses from 5102 slides were analyzed for concordance to
      the general category (GC) and to the reference diagnosis (RD). Nonlinear mixed
      models were used to analyze concordance. RESULTS: - The overall GC concordance
      was 95.2%. The GC type, participant type, and preparation type were significantly
      associated with GC concordance ( P < .001). Concordance for malignant cases was
      higher than it was for benign cases. Cytotechnologists had better GC concordance
      compared to pathologists. ThinPrep (Hologic, Marlborough, Massachusetts) slides
      had the highest GC concordance. Participant type, fluid type, preparation type,
      and participant interpretation were significantly associated with RD concordance
      ( P < .001). Pathologists performed better than cytotechnologists did for RD
      concordance. Pericardial fluid had the lowest RD concordance, especially for
      cases with normal or reactive findings. Modified Giemsa-stained slides performed
      best for lymphoma and hematopoietic malignancy. Small cell carcinoma had the
      highest GC concordance, and its RD concordance was higher in pleural than in
      peritoneal fluids. Adenocarcinoma showed the highest concordance rates for both
      GC and RD. CONCLUSIONS: - This study illustrates the challenges associated with
      interpreting body fluid cytology, particularly in pericardial fluid, and the
      factors that may affect accurate diagnoses. The results also highlight the value
      of using multiple preparation types in challenging cases.

PMID- 29048221
TI  - Editorial Comment on: Management of Colon Perforation During Percutaneous
      Nephrolithotomy: 12 Years of Experience in a Referral Center by Maghsoudi et al.
      (From: Maghsoudi R, Etemadian M, Kashi AH, et al. J Endourol 2017;31:1032-1036).

PMID- 29048222
TI  - Correlations Between Life-Detection Techniques and Implications for Sampling Site
      Selection in Planetary Analog Missions.
AB  - We conducted an analog sampling expedition under simulated mission constraints to
      areas dominated by basaltic tephra of the Eldfell and Fimmvorduhals lava fields
      (Iceland). Sites were selected to be "homogeneous" at a coarse remote sensing
      resolution (10-100 m) in apparent color, morphology, moisture, and grain size,
      with best-effort realism in numbers of locations and replicates. Three different
      biomarker assays (counting of nucleic-acid-stained cells via fluorescent
      microscopy, a luciferin/luciferase assay for adenosine triphosphate, and
      quantitative polymerase chain reaction (qPCR) to detect DNA associated with
      bacteria, archaea, and fungi) were characterized at four nested spatial scales (1
      m, 10 m, 100 m, and >1 km) by using five common metrics for sample site
      representativeness (sample mean variance, group F tests, pairwise t tests, and
      the distribution-free rank sum H and u tests). Correlations between all assays
      were characterized with Spearman's rank test. The bioluminescence assay showed
      the most variance across the sites, followed by qPCR for bacterial and archaeal
      DNA; these results could not be considered representative at the finest
      resolution tested (1 m). Cell concentration and fungal DNA also had significant
      local variation, but they were homogeneous over scales of >1 km. These results
      show that the selection of life detection assays and the number, distribution,
      and location of sampling sites in a low biomass environment with limited a priori
      characterization can yield both contrasting and complementary results, and that
      their interdependence must be given due consideration to maximize science return
      in future biomarker sampling expeditions. Key Words: Astrobiology-Biodiversity
      Microbiology-Iceland-Planetary exploration-Mars mission simulation-Biomarker.
      Astrobiology 17, 1009-1021.

PMID- 29048224
TI  - The Power of Self-Skepticism in Astrobiology.

PMID- 29048223
TI  - Laboratory Investigations on the Survival of Bacillus subtilis Spores in
      Deliquescent Salt Mars Analog Environments.
AB  - Observed features such as recurring slope lineae suggest that liquid water may
      exist on the surface and near-subsurface of Mars today. The presence of this
      liquid water, likely in the form of a brine, has important implications for the
      present-day water cycle, habitability, and planetary protection policies. It is
      possible that this water is formed, at least partially, by deliquescence of
      salts, a process during which hygroscopic salts absorb water vapor from the
      atmosphere and form a saturated liquid brine. We performed laboratory experiments
      to examine the ability of Bacillus subtilis (B-168) spores, alone or mixed with
      calcium perchlorate salt (Ca(ClO4)2), to form liquid water via deliquescence
      under Mars-relevant conditions. Spore survival after exposure to these conditions
      was examined. An environmental chamber was used to expose the samples to
      temperature and relative humidity (RH) values similar to those found on Mars, and
      Raman microscopy was used to identify the phases of water and salt that were
      present and to confirm the presence of spores. We found that B-168 spores did not
      condense any detectable water vapor on their own during the diurnal cycle, even
      at 100% RH. However, when spores were mixed with perchlorate salt, the entire
      sample deliquesced at low RH values, immersing the spores in a brine solution
      during the majority of the simulated martian temperature and humidity cycle.
      After exposure to the simulated diurnal cycles and, in some cases, perchlorate
      brine, the impact of each environmental scenario on spore survival was estimated
      by standard plate assay. We found that, if there are deliquescent salts in
      contact with spores, there is a mechanism for the spores to acquire liquid water
      starting with only atmospheric water vapor as the H2O source. Also, neither
      crystalline nor liquid Ca(ClO4)2 is sporicidal despite the low water activity.
      Key Words: Raman microscopy-Mars-Planetary protection-Salts-Water activity.
      Astrobiology 17, 997-1008.

PMID- 29048225
TI  - Protecting Our Investment in the Exploration and Utilization of Space.

PMID- 29048226
TI  - Effect of Laser Settings and Irrigation Rates on Ureteral Temperature During
      Holmium Laser Lithotripsy, an In Vitro Model.
AB  - PURPOSE: Ureteroscopic laser lithotripsy requires irrigation for adequate
      visualization and temperature control during treatment of ureteral stones.
      However, there are little data on how different irrigation and laser settings
      affect the ureteral wall and surrounding tissues. This effect has become an
      important consideration with the advent of high-powered lasers. We therefore
      evaluated the effect of laser settings and irrigation flow on ureteral
      temperature in an in vitro setting. MATERIALS AND METHODS: To mimic ureteroscopic
      laser lithotripsy, we simulated clinically relevant irrigation flow rates and
      fired a Holmium:Yttrium-aluminum-garnet (Ho:YAG) laser while monitoring
      "intraureteral" temperature. The probe tip of a thermometer was placed 1 mm from
      the tip of a 200 MUm laser fiber, which was fired for 60 seconds at 0.2 J/50 Hz,
      0.6 J/6 Hz, 0.8 J/8 Hz, 1 J/10 Hz, and 1 J/20 Hz within a tubing system that
      allowed for specified room temperature flow rates (100, 50, and 0 mL/minute). We
      recorded temperatures every 5 seconds. The maximum temperature was noted, and
      each laser/flow trial was duplicated. Averaged maximum temperatures were compared
      using analysis of variance across irrigation settings. RESULTS: At 100 cc/minute,
      only the 1 J/20 Hz laser setting produced a significantly higher maximum
      temperature (p < 0.01), although this finding was not clinically significant at a
      maximum of 30.7 degrees C. At a lower irrigation rate of 50 cc/minute, the 1 J/20
      Hz setting was again the only significantly higher maximum temperature (p <
      0.05), although this temperature crossed the toxic threshold at a maximum of 43.4
      degrees C. With no flow, all maximum temperatures reached over 43 degrees C, with
      0.8 J/8 Hz, 1 J/10 Hz, and 1 J/20 Hz each statistically higher than the lower
      energy settings (p < 0.05). The maximum temperature at 1 J/20 Hz with no
      irrigation was over 100 degrees C. CONCLUSIONS: Despite increasing laser
      settings, adequate irrigation can maintain relatively stable temperatures within
      an in vitro ureteral system. As irrigation rates decrease, even lower power laser
      settings produce a clinically significant increase in maximum temperature,
      potentially causing ureteral tissue injury.

PMID- 29048227
TI  - Nephrolithiasis Among Middle Aged and Elderly Urban Chinese: A Report from
      Prospective Cohort Studies in Shanghai.
AB  - INTRODUCTION: Kidney stone risk factors are understudied among Asians. Our study
      objective was to investigate associations of obesity and other chronic diseases
      with incident kidney stones among the urban Chinese. PATIENTS AND METHODS:
      Included in this study are two prospective cohorts: the Shanghai Women's Health
      Study (N = 69,166) and Shanghai Men's Health Study (N = 58,054). Incident kidney
      stones were determined by self-report in 2004 and 2008. Cox regression models
      were used to evaluate the associations of study variables with stone risk with
      adjustment of demographics, medical history, and dietary intakes. RESULTS: There
      were 2653 incident stones over 1,007,958 person-years of follow-up. Overall
      incidence rates (per 1000 person-years, 95% confidence interval [CI]) were 2.10
      (1.99, 2.21) among women and 3.80 (3.59, 4.02) among men. Higher body mass index
      (BMI) was associated with risk (BMI >=25 vs 18.5-24.9 kg/m2, women: hazard ratio
      [HR] = 1.14 [95% CI 1.01, 1.28]; men: HR = 1.17 [1.03, 1.32]). High waist-hip
      ratio (>=0.80 and >=0.90 for women and men, respectively) was associated with
      risk (HR 1.13, 95% CI 1.01, 1.27 for women; HR 1.19, 95% CI 1.05, 1.35 for men).
      Coronary heart disease or stroke history was associated with risk in women only
      (HR 1.31, 95% CI 1.10, 1.56). Hypertension history was associated with risk in
      men only (HR 1.27, 95% CI 1.11, 1.45). No significant association with diabetes
      mellitus was observed. CONCLUSIONS: Among the Chinese, kidney stone incidence in
      men is almost twice that of women. Obesity is a shared risk factor. Hypertension
      history is associated with risk in men, whereas history of coronary heart disease
      or stroke is associated with risk in women.

PMID- 29048229
TI  - Editorial Comment on: The Decline of Laparoendoscopic Single-Site Surgery: A
      Survey of the Endourological Society to Identify Shortcomings and Guidance for
      Future Directions by Sorokin et al. (From: Sorokin I, Canvasser NE, Irwin B, et
      al. J Endourol 2017;31:1049-1055).

PMID- 29048228
TI  - Predictive Factors for Achieving Superior Pentafecta Outcomes Following Robot
      Assisted Partial Nephrectomy in Patients with Localized Renal Cell Carcinoma.
AB  - PURPOSE: To examine the perioperative outcomes following robot-assisted partial
      nephrectomy (RAPN) in patients with localized renal cell carcinoma (RCC) and to
      identify the predictors of Pentafecta achievement following RAPN. MATERIALS AND
      METHODS: We retrospectively analyzed the data from 362 patients with RCC who
      underwent RAPN from 2008 to 2016. The criteria for Pentafecta achievement were
      defined as the Trifecta [warm ischemic time (WIT) <=25 minutes, negative surgical
      margin, and no significant perioperative complications]; with the addition of
      renal function preservation, including over 90% preservation of the estimated
      glomerular filtration rate (e-GFR); and no stage upgrade of chronic kidney
      disease at 1 year after surgery. Multivariate logistic regression analysis was
      performed to determine the predictors of the Pentafecta outcomes. RESULTS: Among
      362 patients, 82.3% (n = 298) had clinical T1a tumors. The median tumor size was
      2.9 cm [interquartile range (IQR) = 2.1-3.6] and median nephrometry score was 7
      (IQR = 6-8). The median operative time was 220 minutes (IQR = 185-270) and median
      estimated blood loss was 150 mL (IQR = 100-200). The median WIT was 20 minutes
      (IQR = 16-26). The overall rate of postoperative complications was 18.8% (n =
      68). The rates of Trifecta and Pentafecta achievement were 66.6% (n = 241/362)
      and 33.9% (n = 121/303), respectively. Notably, the preoperative e-GFR,
      hypertension, tumor size, L-component of the R.E.N.A.L score, and surgeon's
      experience were identified as the significant predictors of Pentafecta
      achievement. Additionally, patients with T1a tumors showed higher rates of
      Pentafecta achievement (45.7% vs 25.9%) compared with those of patients with T1b
      tumors. However, there was no significant difference in the Pentafecta
      accomplishment rates between the transperitoneal and retroperitoneal approaches.
      CONCLUSIONS: In summary, our data highlighted that tumor size and nephrometry
      score, which are tumor-related factors, as well as the surgeon's experience, a
      surgeon-related factor, appear to be the critical predictive factors for
      Pentafecta achievement following RAPN.

PMID- 29048230
TI  - The Progress of Breastfeeding Support Programs in the Indian Health Service.

PMID- 29048231
TI  - Ninth Annual Summit on Breastfeeding Participants.

PMID- 29048232
TI  - Ninth Annual Summit on Breastfeeding Agenda.

PMID- 29048233
TI  - Ninth Annual Summit on Breastfeeding Institutions.

PMID- 29048234
TI  - Parent Education for Young Children With Autism and Disruptive Behavior: Response
      to Active Control Treatment.
AB  - This study examines parent and child characteristics in young children with
      autism spectrum disorder and disruptive behavior who showed a positive response
      to a parent education program in a randomized clinical trial of parent training.
      Children with autism spectrum disorder (N = 180) were randomized to parent
      training (PT) or parent education program (PEP) for 6 months. Using the Clinical
      Global Impression-Improvement scale, masked independent evaluators rated positive
      response in 68.5% of children in PT compared to 39.6% in PEP. We compared
      baseline characteristics and change in parental stress, strain, competence, and
      mental health for participants who showed a positive response to PEP (PEP-R) to
      those who did not (PEP-NR). We also compared change in child and parent measures
      for PEP-R participants to those who showed a positive response to PT (PT-R). At
      baseline, PEP-R and PEP-NR participants did not differ on any demographic or
      clinical characteristics. Parents in PEP-R reported significant reductions on the
      Parenting Stress Index, Caregiver Strain Questionnaire, and Parent Health
      Questionnaire, and increases on the Parenting Sense of Competence scale.
      Improvements in child disruptive behavior and parental stress, strain,
      competence, and mental health for PEP-R participants were similar to PT-R
      participants. Vineland Daily Living Skills improved only for children in PT-R.
      PEP was an active control treatment with nearly 40% of participants showing a
      positive response. Change in child disruptive behavior and parental stress,
      strain, competence, and mental health were remarkably similar for participants
      independently rated with a positive response to PEP and PT.

PMID- 29048235
TI  - Role of Constant, Random and Blocked Practice in an Electromyography-Based Oral
      Motor Learning Task.
AB  - PURPOSE: The role of principles of motor learning (PMLs) in speech has received
      much attention in the past decade. Oral motor learning, however, has not received
      similar consideration. This study evaluated the role of three practice conditions
      in an oral motor tracking task. METHOD: Forty-five healthy adult participants
      were randomly and equally assigned to one of three practice conditions (constant,
      blocked, and random) and participated in an electromyography-based task. The
      study consisted of four sessions, at one session a day for four consecutive days.
      The first three days sessions included a practice phase, with immediate visual
      feedback, and an immediate retention phase, without visual feedback. The fourth
      session did not include practice, but only delayed retention testing, lasting 10
      15 minutes, without visual feedback. RESULTS: Random group participants performed
      better than participants in constant and blocked practice conditions on all the
      four days. Constant group participants demonstrated superior learning over
      blocked group participants only on day 4. CONCLUSION: Findings indicate that
      random practice facilitates oral motor learning, which is in line with
      limb/speech motor learning literature. Future research should systematically
      investigate the outcomes of random practice as a function of different oral and
      speech-based tasks.

PMID- 29048236
TI  - "It Just Kind of Happens": College Students' Rationalizations for Blackout
      Drinking.
AB  - Nearly half of college students engage in binge drinking, and blackouts (i.e.,
      episodes of periodic memory loss) represent one common consequence of this
      behavior. Although researchers have begun to understand the extent to which
      students black out, little is known about why they do so. We conducted two
      studies to further our understanding of this risky health behavior. In Study 1,
      we conducted face-to-face interviews (N = 19) to explore students' blackout
      experiences. Our findings suggest that students recognize that blacking out is an
      unhealthy behavior; however, because such a recognition contradicts group norms
      about alcohol consumption, it causes them to experience dissonance, which they
      manage via a variety of rationalization strategies. We investigated these
      findings more systematically through an online survey in Study 2, in which
      students (N = 254) reported on their own and others' beliefs and behaviors about
      blacking out. Our results indicate that many of the rationalization strategies
      students identified in Study 1 were grounded in fallacious reasoning. We discuss
      the collective implications of these findings for future interventions addressing
      students' excessive drinking behaviors.

PMID- 29048237
TI  - Lenvatinib for the Treatment of Radioiodine-Refractory Thyroid Cancer in Real
      Life Practice.
AB  - BACKGROUND: In the Study of (E7080) Lenvatinib in Differentiated Cancer of the
      Thyroid (SELECT) phase 3 trial on advanced radioactive iodine-refractory
      differentiated thyroid cancer (rDTC), lenvatinib improved median progression-free
      survival over placebo by almost 15 months and induces an objective response rate
      of 64.8%, but adverse events occurred in almost all patients. The present study
      evaluates the efficacy and toxicity of lenvatinib treatment in real-life
      practice. METHODS: Clinical charts of 88 consecutive patients treated with
      lenvatinib from July 2015 to June 2016 in 27 French centers were retrospectively
      reviewed. Patients treated for other thyroid cancer types (n = 11) or previously
      treated with lenvatinib within a trial (n = 2) were excluded and the remaining 75
      rDTC patients formed the basis of this report. RESULTS: 75 rDTC patients were
      analyzed (33 females, median age 65 years [range, 35-88 years]), 12 had an
      Eastern Cooperative Oncology Group performance status >=2; 24 cases received
      lenvatinib as first line systemic treatment; 47 (63%) patients had documented
      progressive disease prior to treatment initiation. Distant metastases were
      located in lungs, bones, and lymph nodes (89%, 60%, and 69%, respectively). The
      initial treatment dose was 24 mg in 54 patients and was lower in the other 21
      patients. The median follow-up was 7 months, with a median duration of treatment
      of 6 months [0.3-15]. Median progression-free survival was 10 months. Among the
      65 patients with evaluation of tumor response during treatment, best tumor
      response was a partial response in 23 patients (31%) and stable disease in 38
      (51%). Eleven patients (14.7%) discontinued lenvatinib because of disease
      progression. Forty-four (59%) and 23 (31%) patients had dose reductions or an
      interruption of lenvatinib for adverse events (AEs). The most frequent AEs
      related to treatment were fatigue, hypertension, weight loss, diarrhea, and
      anorexia. Eleven deaths occurred during the study (one considered to be drug
      related). Pneumothorax occurred in 2 patients with lung metastases. CONCLUSIONS:
      Real-life patients with rDTC can benefit from lenvatinib treatment. AEs are
      frequent and should be closely monitored.

PMID- 29048238
TI  - Superiority of a vitamin B12-containing emollient compared to a standard
      emollient in the maintenance treatment of mild-to-moderate plaque psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease affecting 2%-3% of the
      population. The wide range of drugs currently available for its treatment could
      be associated, in the long term, with organ toxicity and adverse events, thus,
      clinical monitoring throughout treatment is required. This investigator-initiated
      trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing
      ointment in comparison with glycerol-petrolatum-based emollient cream used twice
      a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks
      followed by a wash-out observation period of 4 weeks. This study was conducted as
      a randomized, controlled, single-blind, intra-patient left- to right-side trial
      comparing the efficacy and safety of vitamin B12-containing ointment (M
      treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The
      Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time
      points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after
      the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis
      were randomized to receive left- or right-side treatment with B12 ointment. From
      time point T2 to time point F1, there was a statistically significant difference
      in PASI reduction between M-treatment side and C-treatment side. At time point T
      12, the difference between the mean reductions from baseline PASI scores by 5.92
      +/- 2.49 (87, 6%) in the M-treatment side versus 1.08 +/- 1.02 (23, 1%) C
      treatment side was statistically highly significant ( PWex < 0.001). On the
      contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12
      ointment will represent a new concrete therapy option and should be considered in
      the update of therapeutic algorithm for the treatment of psoriasis.

PMID- 29048239
TI  - Community Priorities for Healthy Eating in Older Adults.
AB  - Community planners such as policymakers and health care and nutrition service
      providers can create an "age-friendly" environment to support healthy eating in
      older residents by addressing the highest priorities that enable older adults to
      improve their dietary intake through different food-related community settings.
      To identify and prioritize these factors that facilitate behavioral change
      (enablers) and behavioral settings important for older adult nutrition based on
      the social ecological model, nutrition and aging professionals (n = 30) from two
      rural (West Virginia, Iowa) and two urban (Massachusetts, New York) city/county
      regions (communities) participated in an online or live focus group discussion
      and completed an analytic hierarchy process survey online. Overall, the most
      important perceived enablers were accessibility and cost, followed by
      transportation and social support, but their relative importance varied by
      community. Participants from all communities considered congregate meal sites and
      food banks among the most important behavioral settings. Participants from most
      communities considered food stores to be important and also highlighted other
      settings unique to the area, such as senior housing, neighborhood, and farmers'
      markets. By targeting interventions to address the most notable enablers and
      behavioral settings specific to their community, planning groups can enhance
      their older residents' ability to achieve optimal nutritional health.

PMID- 29048240
TI  - Natural course of posterior subcapsular cataract over a short time period.
AB  - : Purpose/aim of the study: To observe and analyze the weekly changes in
      morphology and size of vacuoles, so called Wedl cells, in eyes with posterior
      subcapsular cataract (PSC). MATERIALS AND METHODS: Thirty-six eyes of 36 patients
      with pronounced PSC were included in this prospective study. High-resolution
      retroillumination images were taken, and the changes in size and shape of Wedl
      cells were analyzed at baseline and at 2 and 4 weeks later using dedicated
      imaging software. RESULTS: In total, 1087 Wedl cells were observed. Within 2 and
      4 weeks, 31 and 22 Wedl cells appeared and 13 and 40 Wedl cells disappeared,
      respectively. Median Wedl cell size at baseline and after 2 and 4 weeks was 4000
      um2 (range: 40-212120 um2), 4080 um2 (range: 40-274520 um2), and 4160 um2 (range:
      40-212200 um2), respectively. For the absolute size change within 4 weeks, a
      significant difference was observed (p = 0.045). The median change in absolute
      solidity within 2 and 4 weeks was 0.01 (range: 0.00-0.19) and 0.02 (range: 0.00
      0.53), respectively. CONCLUSIONS: Wedl cells undergo morphological changes within
      a short time period of 4 weeks and even appearance and disappearance of Wedl
      cells can be observed within weeks. The fact that spontaneous regression occurs
      may, when properly understood, have some relevance for the development of
      therapeutical approaches to reverse existing PSC in the future.

PMID- 29048241
TI  - Nanofibrous Electrospun Heart Decellularized Extracellular Matrix-Based Hybrid
      Scaffold as Wound Dressing for Reducing Scarring in Wound Healing.
AB  - Produced through electrospinning, poly(l-lactide-co-caprolactone) (PLCL)
      membranes, which have a porous structure and are biodegradable, are of interest
      in various medical fields. The porous-structured electrospun membrane is
      particularly interesting because of several favorable properties as follows: it
      exudes fluid from the wound, does not build up under the wound covering, and does
      not cause wound desiccation. Moreover, extracellular matrix (ECM)-based
      structures derived by tissue decellularization have application as engineered
      tissue scaffolds and as supports for cellular regeneration. In particular, heart
      decellularized ECM (hdECM) has various pro-angiogenic factors that can induce
      angiogenesis for wound healing. In this regard, a nanofibrous electrospun hdECM
      based hybrid scaffold (NEhdHS), which is a PLCL membrane, including hdECM as an
      active agent, was tested as a wound dressing to assess its fundamental
      biochemical and physical features in wound healing. Use of NEhdHS with its porous
      structure and pro-angiogenic factors is expected to provide an effective wound
      dressing and reduced scarring. We first demonstrate the effectiveness of a
      proposed decellularization protocol through analysis of dECM components and
      describe the mechanical properties of the fabricated NEhdHS. Next, we present an
      in vitro angiogenesis analysis of the NEhdHS, using a coculture system with human
      dermal fibroblasts and human umbilical vein endothelial cells; the results of
      which confirm its biocompatibility and show that the NEhdHS can significantly
      enhance angiogenesis over that obtained from PLCL or gelatin-containing PLCL
      scaffolds. We also studied the effectiveness of the NEhdHS in vivo. Using a rat
      excisional wound-splinting model, we show that covering the upper part of the
      wound with NEhdHS significantly reduces scarring in the wound healing process
      compared to that with PLCL or gelatin-containing PLCL scaffolds. Based upon its
      properties, we conclude that the NEhdHS has potential for application in wound
      dressing.

PMID- 29048242
TI  - QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of
      Olmesartan medoxomil employing multivariate statistical techniques.
AB  - PURPOSE: This research work entails quality by design (QbD)-based systematic
      development of nanostructured lipid carriers (NLCs) of Olmesartan medoxomil (OLM)
      with improved biopharmaceutical attributes. METHODS: Quality target product
      profile (QTPP) was defined and critical quality attributes (CQAs) were earmarked.
      Solubility of drug was performed in various lipids for screening of them. NLCs
      were prepared by hot-microemulsion method using solid lipids, liquid lipids and
      surfactants with maximal solubility. Failure mode and effect analysis (FMEA) was
      carried out for identifying high risk formulation and process parameters.
      Further, principal component analysis (PCA) was applied on high risk parameters
      for evaluating the effect of type and concentration of lipids and surfactants on
      CQAs. Further, systematic optimization of critical material attributes (CMAs) was
      carried out using face centered cubic design and optimized formulation was
      identified in the design space. RESULTS: FMEA and PCA suggested suitability of
      stearic acid, oleic acid and Tween 80 as the CMAs for NLCs. Response surface
      optimization helped in identifying the optimized NLC formulation with particle
      size ~250 nm, zeta potential <25 mV, entrapment efficiency >75%, in vitro drug
      release >80% within 6 h. Release kinetic modeling indicated drug release through
      Fickian-diffusion mechanism. CONCLUSIONS: Overall, these studies indicated
      successful development of NLCs using multivariate statistical approaches for
      improved product and process understanding.

PMID- 29048243
TI  - Mithramycin A Improves Functional Recovery by Inhibiting BSCB Disruption and
      Hemorrhage after Spinal Cord Injury.
AB  - After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption and
      progressive hemorrhage lead to secondary injury, subsequent apoptosis and/or
      necrosis of neurons and glia, causing permanent neurological deficits. Growing
      evidence indicates that mithramycin A (MA), an anti-cancer drug, has
      neuroprotective effects in ischemic brain injury and Huntington's disease (HD).
      However, the precise mechanism underlying its protective effects is largely
      unknown. Here, we examined the effect of MA on BSCB breakdown and hemorrhage as
      well as subsequent inflammation after SCI. After moderate spinal cord contusion
      injury at T9, MA (150 MUg/kg) was immediately injected intraperitoneally (i.p.)
      and further injected once a day for 5 days. Our data show that MA attenuated BSCB
      disruption and hemorrhage, and inhibited the infiltration of neutrophils and
      macrophages after SCI. Consistent with these findings, the expression of
      inflammatory mediators was significantly alleviated by MA. MA also inhibited the
      expression and activation of matrix metalloprotease-9 (MMP-9) after injury, which
      is known to disrupt BSCB and the degradation of tight junction (TJ) proteins. In
      addition, the expression of sulfonylurea receptor 1 (SUR1) and transient receptor
      potential melastatin 4 (TRPM4), which are known to mediate hemorrhage at an early
      stage after SCI, was significantly blocked by MA treatment. Finally, MA inhibited
      apoptotic cell death and improved functional recovery after injury. Thus, our
      results demonstrated that MA improves functional recovery by attenuating BSCB
      disruption and hemorrhage through the downregulation of SUR1/TRPM4 and MMP-9
      after SCI.

PMID- 29048244
TI  - A pedagogical strategy addressing an unmet need: Making the biology of aging an
      accessible part of interdisciplinary gerontology education.
AB  - In an age of specialization, obstacles to interdisciplinary training and
      integrated intellectual growth are expected. One such obstacle to graduate-level
      training in gerontology is the challenge of making the biology of aging
      accessible to nonbiologists. In this article, the authors' aim is to share 15
      years of experience developing a pedagogical strategy that situates the biology
      of aging as an accessible part of interdisciplinary gerontology education for
      nonbiologists and biologists alike. The approach hinges on a four-pronged
      learning opportunity-four course offerings-that places high priority on
      exactitude with language and sees development of an attitude of precision with
      language as essential to intellectual growth. By inspiring students to master
      language in the key of B-Biology of Aging-we unleash a versatile method for
      developing cross-disciplinary discoverers prepared for a lifetime of seeing and
      reporting.

PMID- 29048245
TI  - Self-Esteem, Internalizing Symptoms, and Theory of Mind in Youth With Autism
      Spectrum Disorder.
AB  - Self-esteem is a potent indicator of mental health in typically developing (TYP)
      individuals. It is surprising that there have been few comprehensive
      investigations of self-esteem in children and adolescents with autism spectrum
      disorder (ASD), given that they are at high risk for comorbid mental health
      problems, such as depression and anxiety. The objectives of the current study
      were to assess how youth with ASD rate their self-esteem compared to age-matched
      TYP youth and to examine how self-esteem relates to internalizing psychopathology
      and theory of mind in the two groups. Seventy-three children and adolescents,
      ages 9 to 17, were administered a battery of questionnaires assessing self-esteem
      and internalizing symptoms, as well as tasks designed to measure theory of mind.
      Results indicated that youth with ASD rated their self-esteem significantly lower
      than did TYP youth. Self-esteem was strongly related to depression in both groups
      but was negatively related to theory of mind only for youth with ASD. These
      results may provide important insights into how individuals with ASD form
      evaluations of their own self-worth and illustrate how increasing self-awareness
      in individuals with ASD is not without risks.

PMID- 29048246
TI  - Home-based care: barriers and facilitators to expanded personal support worker
      roles in Ontario, Canada.
AB  - To accommodate the increasing demand for home care in Ontario, Canada, some care
      tasks traditionally performed by regulated health professionals are being
      transferred to personal support workers (PSW). However, this expansion of PSW
      roles is not uniform across the province. Between December 2014 and April 2015,
      barriers and facilitators to expansion of PSW roles in home care were explored in
      a series of 13 focus groups. Home care staff identified seven categories of
      factors affecting the expansion of PSW roles in home care including:
      communication and documentation; organization and structures of care; attitudes
      and perceptions of the expanding PSW role; adequate staffing; education, training
      and support; PSW role clarity and variation in practices, policies, and
      procedures. Addressing barriers and promoting facilitators at the funder and
      employer levels will enable the provision of safe, effective, and equitable care
      by PSWs.

PMID- 29048247
TI  - Spatio-temporal dynamics of the mirror neuron system during social intentions.
AB  - Previous research has shown that specific goals and intentions influence a
      person's allocation of social attention. From a neural viewpoint, a growing body
      of evidence suggests that the inferior fronto-parietal network, including the
      mirror neuron system, plays a role in the planning and the understanding of motor
      intentions. However, it is unclear whether and when the mirror neuron system
      plays a role in social intentions. Combining a behavioral task with electrical
      neuroimaging in 22 healthy male participants, the current study investigates
      whether the temporal brain dynamic of the mirror neuron system differs during two
      types of social intentions i.e., lust vs. romantic intentions. Our results showed
      that 62% of the stimuli evoking lustful intentions also evoked romantic
      intentions, and both intentions were sustained by similar activations of the
      inferior frontal gyrus and the inferior parietal lobule/angular gyrus for the
      first 432 ms after stimulus onset. Intentions to not love or not lust, on the
      other hand, were characterized by earlier differential activations of the
      inferior fronto-parietal network i.e., as early as 244 ms after stimulus onset.
      These results suggest that the mirror neuron system may not only code for the
      motor correlates of intentions, but also for the social meaning of intentions and
      its valence at both early/automatic and later/more elaborative stages of
      information processing.

PMID- 29048248
TI  - Rationale and development of a patient-tailored complex intervention of case
      management for patients suffering from chronic obstructive pulmonary disease.
AB  - This article describes the rationale, considerations, and choices made in
      developing a complex intervention evaluating the effectiveness and cost
      effectiveness of community-based case management for chronic obstructive
      pulmonary disease patients in a Danish setting. Inspired by the existing research
      methods for designing complex interventions, the intervention was developed using
      mixed methods entailing systematic review of available literature, interviews
      with key stakeholders, and discussions in a specialist-comprised project group.
      The rigorous process helped develop an intervention that properly accounted for
      both available evidence and context of the setting. We encourage researchers to
      provide a transparent reporting of the process behind intervention development.

PMID- 29048249
TI  - Effect of Teaching Races for Understanding in Youth Sailing on Performance,
      Knowledge, and Adherence.
AB  - PURPOSE: The purpose of this study was to know whether an intervention using an
      adaptation of the teaching games for understanding approach (named teaching races
      for understanding [TRfU]) led participants to improve skill execution, decision
      making, race performance, race involvement, race knowledge, enjoyment, intention
      to continue practicing sailing, and perceived competence. METHOD: Participants
      were 67 children from a randomly selected sailing school (Mage = 9.32 years, SD =
      2.60 years) and 2 coaches. We designed and validated the TRfU lessons, and 1
      coach was trained in the approach. The TRfU group participated in 11 lessons.
      This study followed a mixed-methods data approach. Quantitative data were
      evaluated using a quasiexperimental pretest-posttest design with a control group.
      The intervention consisted of teaching sailing using the TRfU approach. Children
      and coaches' perceptions were evaluated through an interview on completion of the
      study. Data were collected using an adaptation of the Game Performance Assessment
      Instrument, a knowledge questionnaire, 2 psychological scales, and interviews
      with children and coaches. RESULTS: The TRfU group showed statistically
      significant improvements in skill execution, decision making, and race
      performance compared with the control group, as well as significant improvements
      in race involvement, race knowledge, and enjoyment (ES = 0.64-2.63). CONCLUSION:
      Teaching races for understanding can be used in sailing to improve students'
      capacity to reflect and connect theoretical knowledge with their motor
      performance in the race.

PMID- 29048251
TI  - Mental Health-Related Outcomes of Robin Williams' Death: The Role of Parasocial
      Relations and Media Exposure in Stigma, Help-Seeking, and Outreach.
AB  - This study explores responses to the death of actor/comedian Robin Williams,
      focusing on the role of celebrity attachment and exposure to media coverage
      following his suicide. A total of 350 respondents recruited on Mechanical Turk
      completed an online survey. Participants who had a stronger parasocial
      relationship with Williams reported lower social distance from people with
      depression, greater willingness to seek treatment for depression, and more
      frequent outreach to other people with depression or suicidal thoughts following
      his death. Exposure to media coverage of suicide/depression - both informational
      and stigmatizing - was associated with more frequent outreach to others, but only
      informational coverage was related to greater willingness to seek treatment.
      Stigmatizing media exposure was related to greater depression stereotypes. Seeing
      more media stories celebrating Williams' life and career was associated with
      reduced depression stigma but also with less willingness to seek treatment for
      depression and less outreach to others. Implications of the findings for media
      and mental health are discussed.

PMID- 29048250
TI  - Inhibition of Abeta Proteotoxicity by Paeoniflorin in Caenorhabditis elegans
      Through Regulation of Oxidative and Heat Shock Stress Responses.
AB  - Alzheimer's disease (AD) is a common form of dementia and amyloid-beta peptide
      (Abeta) aggregation is considered to be one of its main causes. Paeoniflorin has
      been previously shown to attenuate cognitive damage inflicted by exogenous Abeta
      protein. Using transgenic Caenorhabditis elegans models expressing human Abeta1
      42, we demonstrate here that paeoniflorin can delay progressive paralysis caused
      by endogenous Abeta expression and reduce the amount of toxic Abeta oligomers in
      vivo, although it has no effect on Abeta aggregation in vitro. Paeoniflorin does
      not, however, affect the lifespan of either wild-type or AD-like nematodes,
      implying a mechanism independent of a general antiaging effect. We then
      demonstrate that paeoniflorin can reduce reactive oxygen species levels in C.
      elegans AD models, which may contribute to its in vivo suppression of Abeta
      toxicity. Moreover, paeoniflorin is shown to upregulate the expression of the
      small heat shock protein HSP-16.2 as it is capable of increasing the hsp-16.2
      transcript level in wild-type as well as AD-like nematodes and enhancing the
      fluorescence intensity in hsp-16.2::GFP nematodes. Taken together, our findings
      demonstrate the underlying mechanisms of the protective effect of paeoniflorin
      against age-onset Abeta proteotoxicity, which are, in part, connected with
      oxidative and heat shock stress responses.

PMID- 29048252
TI  - Stigma Communication Surrounding PrEP: The Experiences of A Sample of Men Who
      Have Sex With Men.
AB  - HIV is a serious problem in the USA, particularly for men who have sex with men
      (MSM). A new means of HIV prevention, called pre-exposure prophylaxis (PrEP), has
      been shown to be highly effective. However, in spite of earning FDA approval,
      adoption of PrEP by MSM has been limited. The purpose of this study was to
      examine the experiences of a sample of 38 MSM who have adopted PrEP, focusing on
      communication with healthcare providers and social networks. In-depth interviews
      were used to collect data. Findings revealed that stigmatization by healthcare
      providers as well as stigmatization by other MSM was a relatively common
      experience for participants. Additionally, participants described that a high
      level of health literacy, health advocacy, and communication skill were necessary
      to adopt PrEP. Given these findings, strategies are suggested for improving MSM's
      healthcare and increasing rates of PrEP adoption.

PMID- 29048253
TI  - The Intersections of Science and Practice: Examples From FitnessGram(r)
      Programming.
AB  - The FitnessGram(r) program has provided teachers with practical tools to enhance
      physical education programming. A key to the success of the program has been the
      systematic application of science to practice. Strong research methods have been
      used to develop assessments and standards for use in physical education, but
      consideration has also been given to ensure that programming meets the needs of
      teachers, students, parents, and other stakeholders. This essay summarizes some
      of these complex and nuanced intersections between science and practice with the
      FitnessGram(r) program. The commentaries are organized into 5 brief themes:
      science informing practice; practice informing science; balancing science and
      practice; promoting evidence-based practice; and the integration of science and
      practice. The article draws on personal experiences with the FitnessGram(r)
      program and is prepared based on comments shared during the 37th Annual C. H.
      McCloy Research Lecture at the 2017 SHAPE America - Society of Health and
      Physical Educators Convention.

PMID- 29048254
TI  - Dressing "in code": Clothing rules, propriety, and perceptions.
AB  - Does dressing in line with societal clothing rules make a woman appear more
      professional and competent? We used a within-subjects design and tested if
      participants rated women dressed in compliance with school and workplace clothing
      rules more positively than women not dressed in compliance with rules.
      Participants (N = 89) at a mid-sized mid-western university rated 10 pictures of
      women captured from the internet on 11 attributes. Participants rated the five
      women dressed following clothing rules higher on a composite measure of positive
      attributes (intelligent, competent, powerful, organized, efficient, and
      professional), F(1, 86) = 68.92, p < .001 etap2 = .45. Participant's ratings did
      not correlate with their own self-reported levels of sexism. Participants' gender
      was not a significant correlate. Our findings indicate that how students perceive
      women significantly relates to dressing in code. Participants rated women in less
      revealing and less tight clothing more positively.

PMID- 29048255
TI  - Quality of life in patients with unilateral vestibular schwannoma on wait and see
      - strategy.
AB  - OBJECTIVE: A 'wait and see' strategy is an option when managing patients with
      small vestibular schwannomas (VS). A risk of growth and worsening of hearing may
      influence a patient's daily quality of life (QOL). Therefore, the present study
      focused on QOL parameters in patients who are on a 'wait and see' strategy
      following magnetic resonance imaging (MRI)-based diagnosis of small unilateral
      VS. PATIENTS AND METHODS: Sixty-five patients (mean age 64.4 years; male:female,
      32:33) who suffered from a small unilateral VS (9.34 mm, range 1.5-23 mm) between
      2013 and 2016 were included in a prospective single center study. During follow
      up, in addition to clinical and neurological examinations and MRI imaging, all
      patients answered the Short Form 36 questionnaire once to characterize QOL.
      Additionally, the severity of tinnitus was determined by the Mini-TQ-12 from
      Hiller and Goebel. RESULTS: It was found during follow-up that there was no
      lowering of QOL in patients with small VS who were on 'wait and see' strategy
      compared with Germany's general population and no tumor growth was detected in 53
      patients (81.5%). Patients with a tumor diameter larger than 10 mm did not suffer
      from stronger tinnitus, vertigo or unsteadiness than the group with an average
      tumor size, which is smaller than 10 mm. Sixty-two patients (95.4%) showed
      ipsilateral hearing loss and three of these reported deafness (4.6%). Severe
      vertigo or tinnitus is connected with lower levels of mental component scale and
      physical component scale. These findings reduced the QOL (p = 0.05). CONCLUSION:
      In our series, QOL is not influenced in patients with unilateral untreated small
      VS in comparison to Germany's general population. This is helpful information
      when advising patients during follow-up and finding out the optimal timing of
      individual treatment.

PMID- 29048256
TI  - SKIPing With Head Start Teachers: Influence of T-SKIP on Object-Control Skills.
AB  - PURPOSE: Children from disadvantaged settings are at risk for delays in their
      object-control (OC) skills. Fundamental motor skill interventions, such as the
      Successful Kinesthetic Instruction for Preschoolers (SKIP) Program, are highly
      successful when led by motor development experts. However, few preschools employ
      such experts. This study examined the extent to which Head Start teachers
      delivering an 8-week teacher-led SKIP (T-SKIP) intervention elicited learning of
      OC skills for Head Start children. METHOD: Head Start teachers (n = 5) delivered
      T-SKIP for 8 weeks (450 min). Control teachers (n = 5) implemented the typical
      standard of practice, or well-equipped free play. All children (N = 122) were
      pretested and posttested on the OC Skill subscale of the Test of Gross Motor
      Development-2. RESULTS: Descriptive analyses at pretest identified 81% of the
      children were developmentally delayed in OC skills (below the 30th percentile). A
      2-level hierarchical linear model demonstrated the effectiveness of T-SKIP with
      significant differences (beta = 4.70), t(8) = 7.02, p < .001, eta2 = .56, between
      T-SKIP children (n = 63) and control children (n = 59) at posttest. CONCLUSION:
      Head Start teachers who delivered T-SKIP could bring about positive changes in
      children's OC skills, thereby remediating the initial developmental delays
      presented. Control children remained delayed in their OC skills in spite of daily
      well-equipped free play, giving rise to concerns about their future motor
      competence and physical activity levels.

PMID- 29048257
TI  - Desmopressin acetate nasal spray for adults with nocturia.
AB  - INTRODUCTION: Nocturia impacts 70% of individuals over age 70 years. Nocturnal
      polyuria is present in up to 88% of adults with nocturia, however, treatment
      options for reducing nighttime urine production have historically been limited to
      behavioral modification and off label use of timed diuretics and desmopressin.
      NoctivaTM (desmopressin acetate nasal spray, DANS, Serenity Pharmaceuticals, LLC)
      is a novel formulation of desmopressin approved by the Food and Drug
      Administration for the treatment of nocturia due to nocturnal polyuria in March
      2017. Areas covered: Incidence and etiology of nocturia, currently available
      therapies (approved and off label), and pharmacokinetic, efficacy, and safety
      data associated with DANS. Expert commentary: DANS has been studied for the
      treatment of nocturia in adults over age 50 without contraindications to the use
      of desmopressin. 49% receiving the higher clinical dose experienced >=50%
      reduction in nocturnal voids in clinical trials vs. 30% with placebo. Although
      nadir serum sodium <135 mmol/L was not uncommon (14%), the incidence of sodium
      <=125 mmol/L was rare (1%). DANS therefore appears to benefit a significant
      subset of patients with nocturia while maintaining an acceptable risk profile.
      Given the risks of hyponatremia, education of patients and prescribers in
      contraindications and the importance of monitoring are paramount.

PMID- 29048258
TI  - Selection of Implantation Sites for Transplantation of Encapsulated Pancreatic
      Islets.
AB  - Pancreatic islet transplantation has been validated as a valuable therapy for
      type 1 diabetes mellitus patients with exhausted insulin treatment. However, this
      therapy remains limited by the shortage of donor and the requirement of lifelong
      immunosuppression. Islet encapsulation, as an available bioartificial pancreas
      (BAP), represents a promising approach to enable protecting islet grafts without
      or with minimal immunosuppression and possibly expanding the donor pool. To
      develop a clinically implantable BAP, some key aspects need to be taken into
      account: encapsulation material, capsule design, and implant site. Among them,
      the implant site exerts an important influence on the engraftment, stability, and
      biocompatibility of implanted BAP. Currently, an optimal site for encapsulated
      islet transplantation may include sufficient capacity to host large graft
      volumes, portal drainage, ease of access using safe and reproducible procedure,
      adequate blood/oxygen supply, minimal immune/inflammatory reaction, pliable for
      noninvasive imaging and biopsy, and potential of local microenvironment
      manipulation or bioengineering. Varying degrees of success have been confirmed
      with the utilization of liver or extrahepatic sites in an experimental or
      preclinical setting. However, the ideal implant site remains to be further
      engineered or selected for the widespread application of encapsulated islet
      transplantation.

PMID- 29048259
TI  - Tracings of the north of Europe: Robert Chambers in search of the Ice Age.
AB  - Scottish publisher and naturalist Robert Chambers pursued an amateur interest in
      geology through much of his life. His early measurements of raised beaches in
      Scotland earned him membership in the Geological Society of London in 1844, a
      recognition much appreciated by the anonymous author of the 'scandalous' Vestiges
      published the same year. Although familiar with emerging ice age theories,
      Chambers remained with most British geologists a sceptic through the 1840s, even
      after a trip to the glaciers of the Alps in 1848, which nevertheless prepared him
      for the turning point, which came in 1849 during an extensive field trip in
      Norway and Sweden. Here a wealth of observations left him in no doubt that vast
      glaciers had formerly covered Scandinavia, polishing cliffs, scouring striations,
      depositing old moraines and erratic boulders. This also led him to a new glacial
      reading of the British landscape, and with the ardent conviction of a fresh
      convert he became one of the most vocal supporters of glacial theory in Britain
      in the 1850s at a time when the iceberg drift theory for boulder transport was
      still favoured by most prominent British geologists. While Chambers through his
      popular Chambers's Edinburgh Journal communicated his travels and ice age vision
      to a wide audience, and also pointed out ice age evidence on guided excursions
      around Edinburgh, he did not enter this new vision into subsequent editions of
      Vestiges, probably in order not to reveal its author. This paper explores
      Chambers's contributions to the ice age debate, his field trips and the genesis
      of his convictions, and evaluates his impact on the scientific debate.

PMID- 29048260
TI  - Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) confirms that
      abaloparatide is a valuable addition to the armamentarium against osteoporosis.
AB  - The recently published Abaloparatide Comparator Trial in Vertebral Endpoints
      (ACTIVE) assessed the efficacy and safety of abaloparatide (80 ug daily
      subcutaneous) (ABL) vs placebo during 18 months, in postmenopausal osteoporosis.
      Teriparatide (20 ug daily subcutaneous) (TPD) was used as an open label active
      comparator. The results of the study suggest that ABL increases bone mineral
      density more than TPD and reduces major osteoporotic fractures to a greater
      extent than TPD with a more rapid onset of action. These outcomes combined with a
      positive safety profile make ABL an interesting addition to the armamentarium
      against postmenopausal osteoporosis.

PMID- 29048261
TI  - Postpartum Mothers' Leisure-Time Exercise Behavior is Linked to Positive Emotion
      During Partner Discussions.
AB  - PURPOSE: Marital dissatisfaction and conflict often increase for couples after
      the birth of a child and are evident in fewer positive family interactions and
      more negative family interactions. Because exercise is known to increase positive
      emotions and decrease negative emotions, the current study examined the extent to
      which higher levels of mothers' exercise during the postpartum period were
      related to more positive and fewer negative emotion-expressive behaviors with
      their infants' fathers. METHOD: Mothers' (N = 46; M = 8 months postpartum)
      positive and negative expressive behaviors were coded during couples' discussions
      of current conflict and positive family experiences. Mothers self-reported their
      leisure-time exercise behavior. RESULTS: First-time mothers and mothers with
      higher levels of leisure-time exercise behavior displayed higher levels of
      positive expressive behaviors during couples' discussions. CONCLUSIONS: Exercise
      may be associated with increased positive emotion and, in turn, can have great
      potential to improve family relationships during the postpartum period when
      marital stress normatively increases, particularly for mothers with more than 1
      child. Future longitudinal studies are needed to understand exercise patterns
      across the postpartum period to identify the most effective timing and optimal
      level of exercise that lead to more positive expressive behaviors.

PMID- 29048262
TI  - Genetic and Environmental Influences on Developmental Milestones and Movement:
      Results From the Gemini Cohort Study.
AB  - PURPOSE: Variability in the timing of infant developmental milestones is poorly
      understood. We used a twin analysis to estimate genetic and environmental
      influences on motor development and activity levels in infancy. METHOD: Data were
      from the Gemini Study, a twin birth cohort of 2,402 families with twins born in
      the United Kingdom in 2007. Parents reported motor activity level for each of the
      twins at age 3 months using the Revised Infant Behavior Rating Scale and reported
      the ages at which they first sat unsupported, crawled, and walked unaided.
      RESULTS: Activity level at 3 months and ages when first sitting and crawling were
      about equally influenced by the shared family environment (45%-54%) and genes
      (45%-48%). Genetic influences dominated for age when children took their first
      independent steps (84%). CONCLUSION: Aspects of the shared family environment
      appear to be important influences on motor activity levels and early milestones,
      although the timing of walking may have a stronger genetic influence. Further
      research to identify the specific environmental and genetic factors that promote
      early activity may be important for longer-term health outcomes.

PMID- 29048263
TI  - CAPTURE AND IMMOBILIZATION OF AFRICAN WOLVES ( CANIS LUPASTER) IN THE ETHIOPIAN
      HIGHLANDS.
AB  - :  We captured 14 individual African wolves ( Canis lupaster) a total of 16 times
      in the Ethiopian Highlands in April 2015 and March 2016 by using rubber-lined
      foothold traps and immobilized them with dexmedetomidine-ketamine. Traps were
      baited with sheep meat and surveyed every 2 h. Capture efficiency (number of
      captures per number of visits) was 0.94, and capture rate (number of captures per
      number of trap nights) was 0.24. Trapped wolves were immobilized with 0.025 mg/kg
      dexmedetomidine and 8-10 mg/kg ketamine on the basis of respective estimated body
      mass. Mean (SD) induction times were 3.4 (0.5) min for subadults ( n=4), 3.5
      (0.3) min for adult males ( n=4), and 4.7 (1.0) min for adult females ( n=6).
      Inductions were calm, muscle relaxation was good, and all animals were completely
      immobilized. Apart from increased rectal temperatures, no major negative side
      effects were observed. Atipamezole at 10 mg intramuscularly per milligram of
      dexmedetomidine administered was used for reversal at a mean of 43.5 (7.7) min
      after administration of dexmedetomidine-ketamine. Recoveries were relatively
      smooth, and animals were on feet, leaving the site within a mean of 13.6 (3.9)
      min, after atipamezole administration. Our results indicate that African wolves
      can be safely captured and immobilized by using rubber-lined foothold traps and
      dexmedetomidine and ketamine.

PMID- 29048264
TI  - Counseling parents at risk of delivery of an extremely premature infant:
      Differing strategies.
AB  - BACKGROUND: It is not known how neonatologists address the affective and
      cognitive loads on parents deciding whether to resuscitate infants born extremely
      preterm. This study explores expert neonatologists' views on these decision
      making processes and their own roles in counseling parents. METHODS:
      Semistructured interviews asked internationally recognized experts to share their
      perspectives on perinatal consultations. Their responses were subjected to
      thematic analysis. RESULTS: Eighteen of 22 invited experts participated.
      Approximately equal numbers reported employing a physician-driven approach, a
      parent-driven approach, and a combined approach during these consultations. Those
      who followed a physician-driven approach typically focused on conveying standard
      information about adverse outcomes. Those who followed a parent-driven approach
      typically focused on addressing parents' information requests, guiding their
      decision making, and providing affective support. Nearly all experts, in each
      group, endorsed addressing the child's quality of life, in terms of
      functionality, when discussing long-term outcomes. Although many believed that
      families adjusted to life with a disabled child, few discussed the topic during
      prenatal consultations. Most, in each group, reported trying to alleviate future
      "decisional regret" for parents whose premature infants subsequently became
      disabled. None spoke to parents about possible decisional regret after deciding
      to forgo resuscitation. CONCLUSIONS: Expert neonatologists are deeply concerned
      that parents understand the decision facing them. However, they differ on what
      information they offer and how they balance parents' need for cognitive and
      affective support. They expressed more concern about parents' decisional regret
      should their child survive resuscitation, but have severe disability, than about
      decisional regret after foregoing resuscitation.

PMID- 29048265
TI  - BOOTSTRAPPING BIOLOGY.
AB  - Sarah Webb explores how DIYbio strategies are helping biologists in traditional
      labs do better science.

PMID- 29048266
TI  - SEQUENCING BRAIN CELLS.
AB  - Cataloging different cell types in the human brain remains a challenge for
      neuroscientists. Janelle Weaver speaks to researchers who think single-cell
      sequencing might provide a solution.

PMID- 29048267
TI  - Image-based cell-size estimation for baculovirus quantification.
AB  - Measurement of virus concentration is essential for effective virus-based
      transfection technologies. Here, we describe a user-friendly, image-based cell
      size estimation (ICSE) assay for baculovirus quantification that relies on
      automated determination of cell diameters from bright-field microscopy images. In
      the ICSE assay, microplate-based imaging systems and our custom ICSE-Tools
      software enable measurement of cell morphological parameters over time. Results
      from the ICSE assay were in agreement with virus concentration measurements
      obtained using the traditional plaque assay as well as the Coulter principle
      based cell-size measurement assay. ICSE-Tools is designed for data organization
      and image analysis from microplate-based imaging systems, and is freely available
      at www.gpcr.ut.ee/software.html.

PMID- 29048268
TI  - Density separation of quiescent yeast using iodixanol.
AB  - As yeast are starved of nutrients, they enter G0, a quiescent state. Quiescent
      yeast (Q) cells retain viability for extended periods of time and resume growth
      following supplementation of missing nutrients. As such, Q cells have become a
      valuable model for studying longevity and self-renewal of chronologically aged
      cells. Traditional isolation of Q cells involves a relatively long centrifugation
      time through a continuous density gradient. Here, we describe a rapid and cost
      effective Q-cell isolation technique that uses a single-density, one-step
      gradient prepared from media containing iodixanol.

PMID- 29048269
TI  - An improved collagen zymography approach for evaluating the collagenases MMP-1,
      MMP-8, and MMP-13.
AB  - Collagen zymography is an SDS-PAGE-based method for detecting both the proenzyme
      and active forms of collagenases. Although collagen zymography is used for
      assessment of the matrix metalloproteinases MMP-1 and MMP-13, it can be difficult
      to detect these collagenases due to technical issues. Moreover, it remains
      unclear whether the collagenase activity of MMP-8 can be detected by this method.
      Here, we present an improved collagen zymography method that allows
      quantification of the activities of MMP-1, MMP-8, and MMP-13. Activities of
      recombinant collagenases could be detected in collagen zymogram gels
      copolymerized with 0.3 mg/mL type I collagen extracted from rat tail tendon. This
      improved method is sensitive enough to detect the activity of as little as 1 ng
      of collagenase. We generated standard curves for the three collagenases to
      quantify the collagenolytic activity levels of unknown samples. To validate our
      improved method, we investigated MMP-1 activity levels in human thyroid cancer
      (8505C) and normal thyroid (Nthy-ori-3-1) cell lines, finding that the proenzyme
      and active MMP-1 levels were greater in 8505C cells than in Nthy-ori-3-1 cells.
      Taken together, our data show that collagen zymography can be used in both
      molecular and clinical investigations to evaluate collagenase activities in
      various pathological conditions.

PMID- 29048270
TI  - Genotyping live fish larvae: Non-lethal and noninvasive DNA isolation from 3-5
      day old hatchlings.
AB  - Genotyping fish larvae is a valuable technique for numerous fields of study.
      While methods for collecting DNA from early stage larvae have been published, a
      non-lethal, non-invasive genotyping protocol for hatchlings that is amenable to
      high-throughput approaches is desirable. Here, we describe a method to
      individually genotype live, free-swimming, early fish larvae by characterizing
      their environmental DNA (eDNA). We demonstrate the utility of the method by
      assigning parentage to a sample (n = 50) of 3-5-day-old sheepshead minnow
      (Cyprinodon variegatus) larvae hatchlings, with very high rates of genotyping
      success (98%) and survival (92%) using mitochondrial and microsatellite DNA data.
      This method could be easily adapted to characterize early fish larvae from other
      model and non-model fish species, such as Danio rerio (zebrafish) and Medaka
      medaka.

PMID- 29048271
TI  - MicroScale Thermophoresis (MST) for studying actin polymerization kinetics.
AB  - Here, we present a MicroScale Thermophoresis (MST)-based assay for in vitro
      assessment of actin polymerization. By monitoring the thermophoretic behavior of
      ATTO488-labeled actin in a temperature gradient over time, we could follow
      polymerization in real time and resolve its three characteristic phases:
      nucleation, elongation, and steady-state equilibration. Titration experiments
      allowed us to evaluate the effects of actin-binding proteins (ABPs) on
      polymerization, including DNase I-induced inhibition and mDia2FH1FH2 (mDia2)
      assisted acceleration of nucleation. The corresponding rates of actin filament
      elongation were quantitatively determined, yielding values in good agreement with
      those obtained using the pyrene-actin polymerization assay. Finally, we measured
      the effect of myosin on actin polymerization, circumventing the problems of
      fluorescence quenching and signal disturbance that occur with other techniques.
      MST is a simple and valuable research tool for investigating actin kinetics
      covering a wide range of molecular interactions, with low protein consumption.

PMID- 29048273
TI  - Chiari 1000 Registry Project: assessment of surgical outcome on self-focused
      attention, pain, and delayed recall.
AB  - BACKGROUND: Prior research has typically found a negative relationship between
      chronic pain and memory, and we examined whether cognitive control processes
      (e.g. reflection and rumination) moderated this relationship in individuals with
      Chiari malformation Type I (CM). CM is a neurological condition in which the
      cerebellar tonsils descend into the medullary and upper cervical spine regions
      potentially resulting in severe headaches and neck pain. METHODS: CM patients who
      had (n = 341) and had not (n = 297) undergone decompression surgery completed the
      McGill Pain Questionnaire-Short Form-Revised (SF-MPQ-2), the Rey Auditory Verbal
      Learning Test (RAVLT), and the Rumination-Reflection Questionnaire (RRQ).
      Immediate recall scores were compared to those of 102 healthy controls, and
      delayed recall performance was compared across other variables within the CM
      group. RESULTS: CM patients performed more poorly on immediate recall than did
      controls. Within CM patients, we observed main effects for reflection and age,
      and a pain x reflection x surgical status (surgery v. no surgery) interaction in
      which non-decompressed individuals with low levels of pain and high levels of
      reflection showed superior delayed recall relative to non-decompressed
      individuals with higher pain and all decompressed individuals. CONCLUSIONS: CM
      patients show an immediate recall deficit relative to controls, regardless of
      surgical status. High levels of reflection were associated with better delayed
      recall performance in non-decompressed CM patients with lower pain levels. High
      levels of chronic pain may overwhelm increased focused attention abilities, but
      higher levels of reflection partially overcome the distracting effects of pain
      and this may represent a type of resilience.

PMID- 29048274
TI  - Isolation and characterization of a new iflavirus from Armigeres spp. mosquitoes
      in the Philippines.
AB  - During an entomological surveillance for arthropod-borne viruses in the
      Philippines, we isolated a previously unrecognized virus from female Armigeres
      spp. mosquitoes. Whole-genome sequencing, genetic characterization and
      phylogenetic analysis revealed that the isolated virus, designated Armigeres
      iflavirus (ArIFV), is a novel member of the iflaviruses (genus Iflavirus, family
      Iflaviridae) and phylogenetically related to Moku virus, Hubei odonate virus 4,
      slow bee paralysis virus and Graminella nigrifrons virus 1. To our knowledge,
      this is the first successful isolation of iflavirus from a dipteran insect.
      Spherical ArIFV particles of approximately 30 nm in diameter contained at least
      three major structural proteins. ArIFV multiplied to high titres (~109 p.f.u. ml
      1) and formed clear plaques in a mosquito cell line, C6/36. Our findings provide
      new insights into the infection mechanism, genetic diversity and evolution of the
      Iflaviridae family.

PMID- 29048275
TI  - Comparison of in-house IgM and IgG ELISAs for the serodiagnosis of melioidosis in
      Malaysia.
AB  - Melioidosis is an endemic infectious disease in Southeast Asia and northern
      Australia, caused by Burkholderia pseudomallei. However, the incidence rate in
      Malaysia is not well documented. The high mortality rate and broad range of
      clinical presentations require rapid and accurate diagnosis for appropriate
      treatment. This study compared the efficacy of in-house IgM and IgG ELISA methods
      using a local B. pseudomallei strain. The diagnostic accuracy of the in-house IgG
      ELISA was better than that of the IgM ELISA: sensitivity (IgG: 84.71 %, IgM:
      76.14 %) and specificity (IgG: 93.64 %, IgM: 90.17 %); positive predictive value
      (IgG: 86.75 %, IgM: 79.76 %) and negative predictive value (IgG: 92.57 %, IgM:
      89.66 %); likelihood ratio (LR) [IgG: 13.32, IgM: 7.75 (LR+); IgG: 0.16, IgM:
      0.26 (LR-)], and was supported by the observation of the absorbance value in
      comparisons between culture and serology sampling. In-house IgG ELISA was shown
      to be useful as an early diagnostic tool for melioidosis.

PMID- 29048276
TI  - The Breadth of Viruses in Human Semen.
AB  - Zika virus RNA is frequently detected in the semen of men after Zika virus
      infection. To learn more about persistence of viruses in genital fluids, we
      searched PubMed for relevant articles. We found evidence that 27 viruses, across
      a broad range of virus families, can be found in human semen.

PMID- 29048277
TI  - Retrospective Observational Study of Atypical Winter Respiratory Illness Season
      Using Real-Time Syndromic Surveillance, England, 2014-15.
AB  - During winter 2014-15, England experienced severe strains on acute health
      services. We investigated whether syndromic surveillance could contribute to
      understanding of the unusually high level of healthcare needs. We compared trends
      for several respiratory syndromic indicators from that winter to historical
      baselines. Cumulative and mean incidence rates were compared by winter and age
      group. All-age influenza-like illness was at expected levels; however, severe
      asthma and pneumonia levels were above those expected. Across several respiratory
      indicators, cumulative incidence rates during 2014-15 were similar to those of
      previous years, but higher for older persons; we saw increased rates of acute
      respiratory disease, including influenza like illness, severe asthma, and
      pneumonia, in the 65-74- and >75-year age groups. Age group-specific statistical
      algorithms may provide insights into the burden on health services and improve
      early warning in future winters.

PMID- 29048278
TI  - Mycobacterium lepromatosis Lepromatous Leprosy in US Citizen Who Traveled to
      Disease-Endemic Areas.
AB  - We report Mycobacterium lepromatosis infection in a US-born person with an
      extensive international travel history. Clinical symptoms, histopathology, and
      management are similar to those of infections caused by M. leprae. Clinicians
      should consider this pathogen in the diagnosis of patients with symptoms of
      leprosy who have traveled to endemic areas.

PMID- 29048279
TI  - Weather-Dependent Risk for Legionnaires' Disease, United States.
AB  - Using the Nationwide Inpatient Sample and US weather data, we estimated the
      probability of community-acquired pneumonia (CAP) being diagnosed as
      Legionnaires' disease (LD). LD risk increases when weather is warm and humid.
      With warm weather, we found a dose-response relationship between relative
      humidity and the odds for LD. When the mean temperature was 60 degrees -80
      degrees F with high humidity (>80.0%), the odds for CAP being diagnosed with LD
      were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some
      regions (e.g., the Southwest), LD is rarely the cause of hospitalizations. In
      other regions and seasons (e.g., the mid-Atlantic in summer), LD is much more
      common. Thus, suspicion for LD should increase when weather is warm and humid.
      However, when weather is cold, dry, or extremely hot, empirically treating all
      CAP patients for LD might contribute to excessive antimicrobial drug use at a
      population level.

PMID- 29048280
TI  - Changing Demographics and Prevalence of Body Lice among Homeless Persons,
      Marseille, France.
AB  - The prevalence of body lice among 2,288 sheltered homeless persons in the city of
      Marseille during 2000-2017 was 12.2% and significantly decreased over time. We
      report a positive association between body lice infestations and older age,
      duration of stays in France for migrants, frequent consumption of alcohol, and
      tobacco smoking.

PMID- 29048281
TI  - Street Cleaning Trucks as Potential Sources of Legionella pneumophila.
AB  - In 2015, Legionnaires' disease was diagnosed in a street cleaning worker. We
      found Legionella pneumophila serogroup 1 in the water and internal foam from the
      tanks of 2 trucks used by the worker during the incubation period. The internal
      foam was removed, and a Legionella prevention program was implemented.

PMID- 29048282
TI  - Autochthonous Leprosy without Armadillo Exposure, Eastern United States.
AB  - Autochthonous leprosy has been reported in New York City, where there are no wild
      armadillos. Recent autochthonous cases also have been reported in Georgia and
      Florida and blamed on armadillos, including cases with no known armadillo
      exposure. International migration needs to be considered as a cause of
      autochthonous leprosy.

PMID- 29048283
TI  - Unrecognized Dengue Virus Infections in Children, Western Kenya, 2014-2015.
AB  - We detected a cluster of dengue virus infections in children in Kenya during July
      2014-June 2015. Most cases were serotype 1, but we detected all 4 serotypes,
      including co-infections with 2 serotypes. Our findings implicate dengue as a
      cause of febrile illness in this population and highlight a need for robust
      arbovirus surveillance.

PMID- 29048284
TI  - Bartonella quintana and Typhus Group Rickettsiae Exposure among Homeless Persons,
      Bogota, Colombia.
AB  - In 2015, we investigated Bartonella quintana and typhus group rickettsiae in body
      lice from homeless persons in Bogota, Colombia. We found B. quintana-infected
      body lice and seroprevalence of this microorganism in 19% of homeless persons and
      typhus group rickettsiae in 56%. Public health professionals should start
      preemptive measures and active vector control.

PMID- 29048285
TI  - High-Level Fosfomycin Resistance in Vancomycin-Resistant Enterococcus faecium.
AB  - Of 890 vancomycin-resistant Enterococcus faecium isolates obtained by rectal
      screening from patients in Pittsburgh, Pennsylvania, USA, 4 had MICs >1,024
      MUg/mL for fosfomycin. These isolates had a Cys119Asp substitution in the active
      site of UDP-N-acetylglucosamine enolpyruvyl transferase. This substitution
      increased the fosfomycin MIC >4-fold and rendered this drug inactive in
      biochemical assays.

PMID- 29048286
TI  - Paracoccidioidomycosis after Highway Construction, Rio de Janeiro, Brazil.
AB  - Transmission of Paracoccidioides spp. fungi to humans is usually related to
      manipulation of soil. Rural workers are the most affected group. We report an
      outbreak of paracoccidioidomycosis after deforestation and massive earth removal
      during construction of a highway in Rio de Janeiro, Brazil. Extensive
      environmental disturbances might be involved in fungal transmission.

PMID- 29048287
TI  - Legionella pneumophila Serogroup 1 in the Water Facilities of a Tertiary
      Healthcare Center, India.
AB  - Proactive environmental surveillance for Legionella pneumophila in hospitals that
      treat immunocompromised patients is a useful strategy for preventing nosocomial
      Legionnaires' disease. We report the presence of L. pneumophila serogroup 1 in
      15.2% of the water systems of our tertiary healthcare center, which should prompt
      health officials to formulate mitigation policies.

PMID- 29048288
TI  - Virulence of Japanese Encephalitis Virus Genotypes I and III, Taiwan.
AB  - The virulence of genotype I (GI) Japanese encephalitis virus (JEV) is under
      debate. We investigated differences in the virulence of GI and GIII JEV by
      calculating asymptomatic ratios based on serologic studies during GI- and GIII
      JEV endemic periods. The results suggested equal virulence of GI and GIII JEV
      among humans.

PMID- 29048289
TI  - Outbreak of Zika Virus Infections, Dominica, 2016.
AB  - In February 2016, the World Health Organization declared the pandemic of Zika
      virus a public health emergency. On March 4, 2016, Dominica reported its first
      autochthonous Zika virus disease case; subsequently, 1,263 cases were reported.
      We describe the outbreak through November 2016, when the last known case was
      reported.

PMID- 29048290
TI  - Mycobacterium shimoidei, a Rare Pulmonary Pathogen, Queensland, Australia.
AB  - Nontuberculous mycobacteria are human pathogens with increasing incidence and
      prevalence worldwide. Mycobacterium shimoidei is a rare cause of pulmonary
      disease, with only 15 cases previously reported. This series documents an
      additional 23 cases of M. shimoidei from Queensland, Australia, and highlights
      the pathogenicity and clinical role of this species.

PMID- 29048291
TI  - Diffuse Multibacillary Leprosy of Lucio and Latapi with Lucio's Phenomenon, Peru.
AB  - Diffuse multibacillary leprosy of Lucio and Latapi is mainly reported in Mexico
      and Central America. We report a case in a 65-year-old man in Peru. He also had
      Lucio's phenomenon, characterized by vascular thrombosis and invasion of blood
      vessel walls by leprosy bacilli, causing extensive skin ulcers.

PMID- 29048292
TI  - Pulmonary versus Nonpulmonary Nontuberculous Mycobacteria, Ontario, Canada.
AB  - In Ontario, Canada, during 1998-2010, nontuberculous mycobacteria (NTM) from
      pulmonary sites comprised 96% of species/patient combinations isolated; annual
      rates of isolation and cases increased steadily. NTM isolates from nonpulmonary
      sites comprised 4% of species/patient combinations; annual rates and cases were
      temporally stable. NTM increases were driven exclusively by pulmonary isolates
      and disease.

PMID- 29048294
TI  - Increased Detection of Emergent Recombinant Norovirus GII.P16-GII.2 Strains in
      Young Adults, Hong Kong, China, 2016-2017.
AB  - A new recombinant norovirus GII.P16-GII.2 outnumbered pandemic GII.4 as the
      predominant GII genotype in the winter of 2016-2017 in Hong Kong, China. Half of
      hospitalized case-patients were older children and adults, including 13 young
      adults. This emergent norovirus targets a wider age population compared with
      circulating pandemic GII.4 strains.

PMID- 29048293
TI  - Long-Term Viruria in Zika Virus-Infected Pregnant Women, Brazil, 2016.
AB  - During the 2016 Zika virus outbreak in Brazil, we detected Zika virus RNA in
      urine samples collected from Zika virus-positive pregnant women during different
      stages of pregnancy. Women had positive and negative intervals of viruria; 3
      newborns had adverse outcomes. Further research is needed to clarify the
      relationship between viruria and outcomes for newborns.

PMID- 29048295
TI  - Detection of Spotted Fever Group Rickettsia DNA by Deep Sequencing.
AB  - After conventional molecular and serologic testing failed to diagnose the cause
      of illness, deep sequencing identified spotted fever group Rickettsia DNA in a
      patient's blood sample. Sequences belonged to R. honei, the causative agent of
      Flinders Island spotted fever. Next-generation sequencing is proving to be a
      useful tool for clinical diagnostics.

PMID- 29048296
TI  - Chlamydia trachomatis Biovar L2 Infection in Women in South Africa.
AB  - We detected Chlamydia trachomatis biovar L2 in vaginal swab specimens of 7 women
      with vaginal discharge in South Africa. Whole-genome sequencing directly from
      clinical specimens identified a closely related cluster of strains. The clinical
      role of this infection in the context of syndromic management should be
      clarified.

PMID- 29048297
TI  - Polyclonal Pulmonary Tuberculosis Infections and Risk for Multidrug Resistance,
      Lima, Peru.
AB  - Because within-host Mycobacterium tuberculosis diversity complicates diagnosis
      and treatment of tuberculosis (TB), we measured diversity prevalence and
      associated factors among 3,098 pulmonary TB patients in Lima, Peru. The 161
      patients with polyclonal infection were more likely than the 115 with clonal or
      the 2,822 with simple infections to have multidrug-resistant TB.

PMID- 29048298
TI  - Phylogenetic Analysis of Klebsiella pneumoniae from Hospitalized Children,
      Pakistan.
AB  - Klebsiella pneumoniae shows increasing emergence of multidrug-resistant lineages,
      including strains resistant to all available antimicrobial drugs. We conducted
      whole-genome sequencing of 178 highly drug-resistant isolates from a tertiary
      hospital in Lahore, Pakistan. Phylogenetic analyses to place these isolates into
      global context demonstrate the expansion of multiple independent lineages,
      including K. quasipneumoniae.

PMID- 29048299
TI  - Blood Culture-Negative Endocarditis, Morocco.
AB  - We investigated the microorganisms causing blood culture-negative endocarditis
      (BCNE) in Morocco. We tested 19 patients with BCNE by serologic methods,
      molecular methods, or both and identified Bartonella quintana, Staphylococcus
      aureus, Streptococcus equi, and Streptococcus oralis in 4 patients. These results
      highlight the role of these zoonotic agents in BCNE in Morocco.

PMID- 29048300
TI  - Intensive family exposure-based cognitive-behavioral treatment for adolescents
      with anorexia nervosa.
AB  - BACKGROUND: Anorexia nervosa exhibits high comorbidity rates and shared features
      with anxiety disorders and obsessive-compulsive disorder. Anxiety-based
      etiological models have proposed that fear of eating-related stimuli is the
      central mechanism around which avoidance of food and food-related rituals are
      performed. Building on this approach, exposure-based interventions have
      demonstrated promising results. Limited evidence in adolescents encourages the
      evaluation of exposure approaches in this population. METHOD: The current study
      presents a preliminary evaluation, in eight adolescents with anorexia nervosa, of
      an exposure-based CBT featuring an intensive format and parental involvement.
      RESULTS: significant improvements in physical and psychological outcomes were
      observed. CONCLUSIONS: this case series provides preliminary support for the
      efficacy of intensive family exposure-based CBT for treating adolescents with
      severe anorexia nervosa.

PMID- 29048301
TI  - Beyond the Big Five: the role of extrinsic life aspirations in compulsive buying.
AB  - BACKGROUND: The integration of units of differing natures which are found in
      different parts of some multilevel personality models is one of the most thought
      provoking paths in contemporary research. In the field of compulsive buying,
      little is known about the interrelationships between the comparative and stable
      units such as personality traits (basic tendencies or Level I units) and goals (a
      kind of middle-level unit) which are more related to motivational processes and
      intentions governing people&rsquo;s behavior. METHOD: Self-reporting measures of
      compulsive buying, Big Five personality traits, and extrinsic life aspirations
      were administered to a general population sample consisting of 2,159 participants
      aged 15 to 65 (48.1% males; Mage= 35.4, SD= 13.24). RESULTS: Our results
      confirmed statistically significant associations with compulsive buying for the
      traits as well as the extrinsic goals. Furthermore, an important relationship
      between both levels in personality &ndash; traits vs . extrinsic life aspirations
      &ndash; was found. Finally, extrinsic life aspirations (specially, image,
      popularity, and conformity) contribute to the potentiation of the prediction of
      compulsive buying beyond the Five Factor Model. CONCLUSIONS: Current findings
      emphasize the advisability of considering both levels in personality, traits and
      middle-level units like life aspirations, not only in the prediction of
      compulsive buying, but also as potential targets for preventive and treatment
      programs.

PMID- 29048302
TI  - Pre-symptomatic testing for neurodegenerative disorders: Middle- to long-term
      psychopathological impact.
AB  - BACKGROUND: Over the past 20 years, studies have revealed that the communication
      of a pre-symptomatic test (PST) result for late-onset diseases, such as
      Huntington&rsquo;s disease (HD), doesn&rsquo;t cause psychological disturbance.
      This cross-sectional study investigated the middle- (4 years) to long-term (7 and
      10 years) psychological impact of PST for 3 autosomal dominant late-onset
      diseases: HD, Machado-Joseph disease (DMJ) and familial amyloid polyneuropathy
      (FAP). METHOD: The study included 203 subjects: 170 (84%) agreed to make the PST
      for FAP, 29 (14%) for HD and 4 (2%) for MJD. They were mostly women (58%) and
      married (67%). It was considered the cutoffs points: 4 years (middle-term) and 7
      and 10 years (long-term) indicating the time after receiving the TPS results.
      RESULTS: women and widows (oldest) presented the highest mean values for almost
      all BSI dimensions and the highest values correspond to the obsessive-compulsive
      dimension. MJD participants presented the highest mean values. No differences
      were found concerning the PST test results while participants are still
      asymptomatic. Psychopathology was only present in symptomatic carriers.
      CONCLUSIONS: The onset of the disease seems to assume the trigger for
      psychological disturbance, regardless the time that has elapsed since the PST
      result communication or the individual carrier/non-carrier condition.

PMID- 29048303
TI  - Parental involvement and academic performance: Less control and more
      communication.
AB  - BACKGROUND: Parental involvement in the educational process is desirable,
      although more involvement does not guarantee better results. The aim of this
      research is to explore the relationship between styles of parental involvement at
      home and academic performance. METHOD: A random sample of 26,543 Spanish students
      was used, with a mean age of 14.4 (SD = 0.75). Two thirds (66.2%) attended a
      publicly funded school; 49.7% were girls; 87.8% had Spanish nationality; and
      73.5% were in the school year corresponding to their age. Different three-level
      hierarchical-linear models were fitted: student, school, and region (autonomous
      community). RESULTS: Students whose parents exhibited a more distal or indirect
      profile of family involvement tended to demonstrate better results than those
      from homes with a more controlling style. Parental involvement styles have an
      effect on achievement at an individual and school level, even after accounting
      for the effect of context or background variables. CONCLUSIONS: Given the
      importance of parental involvement in academic performance, schools should
      consider it in their family information and training policies. Schools which have
      more communicative family profiles tend to demonstrate lower levels of intra
      school differences in students&rsquo; academic performance.

PMID- 29048304
TI  - Trustworthiness of a smile as a function of changes in the eye expression.
AB  - BACKGROUND: Trusting other people is necessary for satisfactory and successful
      social interaction. A person&rsquo;s perceived trustworthiness is related to
      perceived facial happiness. We investigated how trustworthy someone with a
      smiling face looks depending on changes in eye expression. METHOD: Video-clips of
      dynamic expressions were presented, with different combinations of the mouth
      (smiling vs. neutral) and the eyes (happy, neutral, surprised, sad, fearful,
      disgusted, or angry). Participants judged how happy (happiness task) or
      trustworthy (trustworthiness task) the expressers were. RESULTS: Both happiness
      and trustworthiness judgments and reaction times varied as a function of small
      changes from happy to non-happy eyes in a smiling face, and depending on the
      specific nature of the eye expression, with angry eyes being particularly
      detrimental. CONCLUSIONS: Perception of facial happiness is more dependent on the
      smiling mouth, whereas trustworthiness relies more on eye expression. Judgments
      of untrustworthiness are especially sensitive to incongruence between the eyes
      and the mouth.

PMID- 29048305
TI  - The effect of demographic variables on the assessment of cognitive ability.
AB  - BACKGROUND: This study examines the effect of parental educational levels, sex,
      and family structure on the WISC-V Full Scale IQ (FSIQ) and primary index scores
      (VCI, VSI, FRI, WMI, and PSI) in a representative sample of children from Spain (
      N = 1008). METHOD: Differences between demographic groups were examined using
      independent-samples t-test , ANOVA and Hochberg post hoc tests. A multiple
      regression analysis was performed to examine whether demographic variables could
      predict children&rsquo;s FSIQ score. RESULTS: Results showed that the
      parents&rsquo; educational level was a significant predictor of children&rsquo;s
      FSIQ and significant increases in mean FSIQ and primary index scores were found
      as the parents&rsquo; educational level increased. Sex was not a significant
      predictor of children&rsquo;s FSIQ but slight sex differences were found for PSI.
      The family structure was a significant predictor of FSIQ but its contribution to
      the global model was small. Children from two-parent families obtained higher
      FSIQ, VCI, VSI, and FRI mean scores than children from single parent families.
      CONCLUSIONS: The results support the design of a normative sample stratified by
      demographic variables. Parental education levels, as a good predictor of
      children&rsquo;s FSIQ score, must be taken into account as a key stratification
      variable.

PMID- 29048306
TI  - Subtle and blatant perceived discrimination and well-being in lesbians and gay
      men in Spain: The role of social support.
AB  - BACKGROUND: The situation of lesbians and gay men (LGs) in Spain has improved
      significantly in recent decades. However, Spanish society still exhibits
      prejudice and discrimination. The current study pursues three main goals: 1) to
      analyse the extent to which LGs perceive blatant and subtle discrimination, 2) to
      explore the relationship between perceived discrimination and LGs&rsquo;
      psychological and subjective well-being, and 3) to analyse the possible
      mediational role of social support in reducing the negative influence of
      perceived discrimination on well-being. METHOD: The sample comprised 237 lesbians
      and 232 gay men. RESULTS: The results show higher perceived subtle than blatant
      discrimination, and that subtle discrimination affects LGs&rsquo; well-being more
      negatively than blatant discrimination. Results show that social support helps to
      alleviate the negative effects of discrimination on well-being. CONCLUSIONS:
      These results are important and may contribute to the design of interventions to
      improve the well-being of lesbians and gay men.

PMID- 29048307
TI  - Assessing aging stereotypes: Personal stereotypes, self-stereotypes and self
      perception of aging.
AB  - BACKGROUND: There is a broad semantic network of aging stereotypes; where
      different concepts and their measurement are confused: personal stereotypes, self
      stereotypes and self-perception of aging. METHOD: First, we analyze the
      translated version of the Image of Aging Scale (IAS) measurement model through
      exploratory and confirmatory factor analysis, with two representative sub-samples
      of the Spanish population aged over eighteen (N = 1,105) and in a sample of
      gerontologists and geriatricians (N = 325). Second, in an effort to disentangle
      the theoretical relationships between personal stereotypes, self-stereotypes and
      self-perception of aging, both the IAS (with different instructions) and
      Lawton&rsquo;s 5-item scale were administered to a representative sample of
      Spanish people over 50. RESULTS: Our results indicate that the Spanish version of
      the IAS has a similar psychometric structure to that proposed by the authors.
      Furthermore, the factorial structure (equal form and metric invariance) is
      replicated in both samples, but latent means and factor correlations were higher
      in the professional group. CONCLUSIONS: We discuss Levy&rsquo;s theoretical
      assumptions about personal-stereotypes and the self-stereotype measured with IAS
      and their relationship to self-perception of ageing.

PMID- 29048308
TI  - Examining police officers' response bias in judging veracity.
AB  - BACKGROUND: Deception detection research has shown that, in judging veracity,
      police officers are less truth biased than non-officers. However, previous
      researchers have normally used videotaped statements where an unknown (but
      presumably large) number of stereotypical or real deception cues are displayed by
      the senders. We examined non-officers, novice officers, and experienced
      officers&rsquo; response tendencies in a more controlled situation where cue
      availability was severely restricted. METHOD: We used written vignettes
      describing either police-related or police-unrelated scenarios where the
      protagonist denied having committed a misdeed. Each vignette contained only two
      pieces of relevant information, one suggesting that the protagonist was lying and
      one suggesting that she or he was telling the truth. RESULTS: Officers made fewer
      truth judgments than non-officers in judging police-relevant vignettes, but not
      in judging police-irrelevant vignettes. Both novice and experienced officers had
      greater judgmental confidence than non-officers. CONCLUSIONS: The findings are
      consistent with the Adaptive Lie Detection Theory (ALIED). Future research should
      continue to explore how the police relevance of the situation or task at hand
      influences novice and experienced officers&rsquo; veracity judgments.

PMID- 29048309
TI  - Sociometric types and academic self-concept in adolescents.
AB  - BACKGROUND: The aim of this study was to analyze the relationship between
      sociometric types, behavioral categories, and academic self-concept in a sample
      of 1,349 (51.7% boys) Spanish adolescents, ranging in age from 12 to 16 years.
      METHOD: the students&rsquo; sociometric nomination was performed using the
      Programa Socio (Partner Program), and academic self-concept was measured with the
      Self Description Questionnaire (SDQ-II; Marsh, 1992). RESULTS: results show that
      academic self-concept was a significant predictor of sociometric types and
      behavioral categories, as students with high scores on academic self-concept were
      more likely to be positively rated by their peers (popular, leaders,
      collaborators and good students) than students with low scores on student
      academic self-concept. CONCLUSIONS: these results reinforce the emphasis on
      academic self-concept research and its relevance to educational practice.

PMID- 29048310
TI  - The evaluation of green companies changes after remembering tip of the tongue
      experiences.
AB  - BACKGROUND: This research explores the extent to which attitudes towards an
      environmentally-friendly topic (a green company) are affected by a &ldquo;tip of
      the tongue&rdquo; (TOT) experience. METHOD: In this experiment, participants were
      first exposed to a description of a green company that elicited mostly positive
      or negative thoughts. As part of an apparently unrelated study, participants were
      then asked to describe an experience of TOT that either was or was not
      successfully resolved. The recalling task was independent from the thoughts about
      the company. Finally, participants reported their attitudes toward the green
      company for which they initially listed thoughts. RESULTS: Participants who
      recalled resolving a TOT experience relied on their thoughts about the initial
      (unrelated) green company more in forming their evaluations than did participants
      who recalled an unresolved TOT experience. CONCLUSION: Attitudes can be affected
      by thinking about an unrelated past meta-cognitive experience.

PMID- 29048311
TI  - Impact of the Intensive Program of Emotional Intelligence (IPEI) on work
      supervisors.
AB  - BACKGROUND: This study aimed to evaluate the effect of the Intensive Program of
      Emotional Intelligence (IPEI; Fern&aacute;ndez, 2016; F&eacute;rreo, 2016) on
      middle managers&rsquo; emotional intelligence, as this variable may have a
      significant impact on personal satisfaction, task performance, and the work
      environment. METHOD: The intervention was applied to work team supervisors in a
      large call center, as it is an overlooked sector in this topic. Two-hundred and
      eighty-two supervisors from a Madrid-based, Spanish multinational (51.4% men and
      48.6% women) participated in this study. Participants were assigned to the
      experimental group (n = 190) or the control group (n = 92) by availability,
      according to management decision. All supervisors filled in two questionnaires to
      evaluate the different components of intrapersonal emotional intelligence (i.e.,
      attention, clarity, and repair; TMMS-24; Fern&aacute;ndez-Berrocal, Extremera, &
      Ramos, 2004) and cognitive and affective empathy (i.e., perspective taking,
      emotion understanding, empathic joy, and personal distress; TECA; L&oacute;pez
      P&eacute;rez, Fern&aacute;ndez, & Abad, 2008). RESULTS: The findings showed an
      increase in the studied variables for the experimental group. CONCLUSIONS: The
      results obtained support middle managers&rsquo; training in emotional competences
      through short, efficient, economic programs. Potential limitations and
      implications of the results are discussed.

PMID- 29048312
TI  - ADHD Symptoms and peer problems: Mediation of executive function and theory of
      mind.
AB  - BACKGROUND: The social maladjustment suffered by many children with attention
      deficit hyperactivity disorder (ADHD) is maintained over time, increasing the
      risk of subsequent adverse outcomes. The objectives of the study were to explore
      the mechanisms that operate between ADHD symptoms and social problems with peers,
      considering the mediation of FE and ToM. METHOD: 35 children with ADHD and 37
      with typical development matched in age and IQ were compared. Parents assessed
      ToM skills and relationships with peers, and teachers provided EF ratings.
      RESULTS: The analyses showed statistically significant indirect mediation effects
      of EF in the relationship between ADHD symptoms and problems in relationships
      with peers, whereas ToM did not show these effects. CONCLUSIONS: EF impairments
      contribute to the social difficulties of children with ADHD.

PMID- 29048313
TI  - Knowledge and attitudes about abortion among undergraduate students.
AB  - BACKGROUND: This study examined attitudes towards and knowledge about abortion
      among undergraduate students doing eleven different subjects. The differences in
      attitudes and knowledge about abortion according to gender, religious and
      political affiliation, religiosity, sexual orientation, number of sex partners
      and previous sexual experience were also considered. METHOD: 1,025 undergraduate
      students (58.34% women and 41.66% men; mean age 20.18) completed the following
      instruments: an adaptation of the Abortion Attitudes Scale by Hill, and an
      adaptation of Abortion Knowledge Test by Esposito and Basow. RESULTS: With
      attitudes ranging from 0 to 100, medicine, psychology and nursing students were
      in the anti-abortion range (55.93, 54.19 and 53.62, respectively) while history,
      philology and physics students were in the pro-abortion rights range (48.44,
      48.49 and 50.12, respectively). Law, medicine and nursing students showed greater
      theoretical knowledge about abortion, while physics, engineering and philology
      students proved to be the least knowledgeable. CONCLUSIONS: Differences were
      found in students&rsquo; attitudes towards abortion and in knowledge about
      abortion depending on their degree subject. As in previous reports, differences
      were found in students&acute; attitudes towards abortion which reflected
      differences in religious affiliation, religiosity, political affiliation, and
      previous sexual experience.

PMID- 29048314
TI  - The effectiveness of a learning strategies program for university students.
AB  - BACKGROUND: University lecturers often complain about their students&rsquo; lack
      of learning strategies, but not many universities in Spain offer specific courses
      in this area. Studies on their effectiveness are also rare. METHOD: This study
      presents the results of a Learning Strategies Course implemented at the School of
      Teacher Training and Education, University of Oviedo, Spain. A quasi-experimental
      design was used with an experi-mental (n = 60) and a control group (n = 57) of
      students on the Educational Psychology course. A Spanish adaptation of the
      Motivated Strategies for Learning Questionnaire (MSLQ): the CEAMR2 was used as a
      pre and post-test measure. Group A (EG) received training in learning strategies,
      while group B (CG) received no training. RESULTS: Post-test measures showed
      significant differences in five out of the ten learning strategies assessed:
      elaboration, organization, repetition, self-questioning and study space, and also
      an improvement in one out of the six motivational scales: control of learning
      beliefs. DISCUSSION: The results suggest that learning strategies courses with
      proven effectiveness should be offered to university students.

PMID- 29048315
TI  - Differences in cognitive, motivational and contextual variables between under
      achieving, normally-achieving, and over-achieving students: A mixed-effects
      analysis.
AB  - BACKGROUND: There are few studies in Spain which analyze the influence of
      individual, motivational and contextual variables, which might be different
      between underachieving, normally achieving and overachieving students. METHOD: A
      total of 1,398 Spanish high school students participated. Mixed-effects models
      were used to analyze data. RESULTS: The results showed some evidence of: (a)
      Partial mediational effect of self-concept on the association between cognitive
      ability and academic achievement. (b) Higher levels of learning goals in the
      overachieving group than in the underachieving group, but no differences in
      achievement and reinforcement goals between groups. (c) Positive effect of
      learning strategies on attainment, both in the underachieving and the non
      underachieving students. (d) Little effect of context variables on academic
      achievement, both in the underachieving and non-underachieving students.
      CONCLUSIONS: underachieving students seem to employ all the learning strategies
      considered to a lesser extent than normally and overachieving students. They also
      have a lower level of learning goals. On the contrary, overachieving students
      score more highly than under and normally achieving students in almost all of the
      above factors.

PMID- 29048316
TI  - The maximum likelihood alignment approach to testing for approximate measurement
      invariance: A paradigmatic cross-cultural application.
AB  - BACKGROUND: The impracticality of using the confirmatory factor analytic (CFA)
      approach in testing measurement invariance across many groups is now well known.
      A concertedeffort to addressing these encumbrances over the last decade has
      resulted in a new generation of alternative methodological procedures that allow
      for approximate, rather than exact measurement invariance across groups. The
      purpose of this article is twofold: (a) to describe and illustrate common
      difficulties encountered when tests for multigroup invariance are based on
      traditional CFA procedures and the number of groups is large, and (b) to walk
      readers through the maximum likelihood (ML) alignment approach in testing for
      approximate measurement invariance. METHODS: Data for this example application
      derive from an earlier study of family functioning across 30 cultures that
      include responses to the Family Values Scale for 5,482 university students drawn
      from 27 of these30 countries. Analyses were based on the Mplus 7.4 program.
      RESULTS: Whereas CFA tests for invariance revealed 108 misspecified parameters
      that precluded tests for latent mean differences, noninvariant results were well
      within the acceptable range for the alignment approach thereby substantiating the
      trustworthiness of the latent mean estimates and their comparison across groups.
      CONCLUSION: The alignment approach in testing for approximate measurement
      invariance provides an automated procedure that can overcome important
      limitations of traditional CFA procedures in large-scale comparisons.

PMID- 29048317
TI  - Non-normal data: Is ANOVA still a valid option?
AB  - BACKGROUND: The robustness of F-test to non-normality has been studied from the
      1930s through to the present day. However, this extensive body of research has
      yielded contradictory results, there being evidence both for and against its
      robustness. This study provides a systematic examination of F-test robustness to
      violations of normality in terms of Type I error, considering a wide variety of
      distributions commonly found in the health and social sciences. METHOD: We
      conducted a Monte Carlo simulation study involving a design with three groups and
      several known and unknown distributions. The manipulated variables were: Equal
      and unequal group sample sizes; group sample size and total sample size;
      coefficient of sample size variation; shape of the distribution and equal or
      unequal shapes of the group distributions; and pairing of group size with the
      degree of contamination in the distribution. RESULTS: The results showed that in
      terms of Type I error the F-test was robust in 100% of the cases studied,
      independently of the manipulated conditions.

PMID- 29048318
TI  - Psychometric properties of a brief on-line screening instrument to detect at-risk
      gamblers.
AB  - BACKGROUND: Gambling facilitates the development of psychopathological problems
      in some gamblers. Rapid and easy detection of the presence of these problems, or
      the risk of their development, will allow early action at the beginning of the
      problem, including preventive action. For this purpose, we developed the
      &ldquo;Sistema de Cribado de Riesgo de Problemas de Juegos&rdquo; (SCRI-PJ [Risk
      of Gambling Problems Screening System]), an on-line instrument for the detection
      of people who have, or may develop, gambling problems. The goal of this work is
      to present and validate the SCRI-PJ. METHOD: 85 people with gambling problems
      undergoing treatment and 119 people from the general population were assessed
      with the SCRI-PJ and the DSM-RT Diagnostic Criteria for Pathological Gambling
      questionnaire. RESULTS: the SCRI-PJ showed high internal consistency (&alpha;=
      .96), sensitivity (94.2%) specificity (91.4%), with a negative predictive value
      of 98.6%. CONCLUSION: the SCRI-PJ is a brief and effective screening instrument
      to detect people with gambling problems or who are at risk of developing them.

PMID- 29048319
TI  - Emotional content in cyberspace: Development and validation of E-motions
      Questionnaire in adolescents and young people.
AB  - BACKGROUND: Studies on emotional intelligence show that some of its dimensions
      are related to psychological adjustment and the quality of interpersonal
      relationships. Besides face-to-face interaction, nowadays, relationships are also
      initiated and maintained in cyberspace. Some studies suggest that emotional
      content is present in cyber-behavior. The objective of this study was to reveal
      whether emotions are expressed, perceived and managed online &ndash; a concept
      called E-motions, and to validate an instrument to measure this concept. METHOD:
      The E-motions Questionnaire was designed and together with other instruments,
      completed by 612 university students. Then, the questionnaire was completed by a
      representative sample of 2139 students in compulsory secondary education in 22
      schools in all Andalusian provinces. The first sample was used for exploratory
      factor analysis and the second sample for confirmatory factor analysis. RESULTS:
      The E-motions Questionnaire was validated with good psychometric properties. Four
      factors were found showing that emotions are perceived, expressed, used,
      understood and managed online. This behavior is related to some aspects of
      emotional intelligence and also to difficulties in identifying feelings.
      CONCLUSIONS: This new promising research field could be useful for further
      advancement of research into cyber-behavior.

PMID- 29048320
TI  - Development of the CarMen-Q Questionnaire for mental workload assessment.
AB  - BACKGROUND: Mental workload has emerged as one of the most important occupational
      risk factors present in most psychological and physical diseases caused by work.
      In view of the lack of specific tools to assess mental workload, the objective of
      this research was to assess the construct validity and reliability of a new
      questionnaire for mental workload assessment (CarMen-Q). METHOD: The sample was
      composed of 884 workers from several professional sectors, between 18 and 65
      years old, 53.4% men and 46.6% women. To evaluate the validity based on
      relationships with other measures, the NASA-TLX scale was also administered.
      RESULTS: Confirmatory factor analysis showed an internal structure made up of
      four dimensions: cognitive, temporal and emotional demands and performance
      requirement. The results show satisfactory evidence of validity based on
      relationships with NASA-TLX and good reliability. CONCLUSIONS: The questionnaire
      has good psychometric properties and can be an easy, brief, useful tool for
      mental workload diagnosis and prevention.

PMID- 29048321
TI  - Spanish validation of the Job Insecurity Scale JIS-8: Viability of the cognitive
      and affective model.
AB  - BACKGROUND: This instrumental study is the Spanish adaptation and validation of
      the Job Insecurity Scale in its 8-item version (JIS-8). This is one of the
      reference tests in this field and it also allows the distinction between affect
      and cognition in quantitative job insecurity to be tested. METHOD: The JIS-8 was
      carried out on a Spanish sample with 592 participants (186 men, 406 women; Mean
      age = 36.68), together with mental health and job satisfaction tests. An
      exploratory factor analysis and confirmatory factor analysis were carried out,
      and the relationship between the scale and other variables was examined. RESULTS:
      The Spanish validation shows good construct validity, internal consistency and a
      Cronbach a = .88, higher than the value obtained in the validation of the
      original instrument. The analysis shows the consequences of job insecurity on
      workers&rsquo; mental health, as well as on their job satisfaction. The
      exploratory factor analysis as well as the confirmatory analysis, in which a one
      dimensional and a two-dimensional model were tested, maintain the presence of two
      factors: the cognitive and the affective dimensions. CONCLUSIONS: The results
      underpin the fact that the test is appropriate for application to people in
      active employment in the Spanish population.

PMID- 29048322
TI  - Psychometric properties of the Aggression Questionnaire: A replication in a
      sample of partner-assaultive men in psychological treatment.
AB  - BACKGROUND: The Aggression Questionnaire (Buss & Perry, 1992) is one of the most
      widely used validated self-report measures to assess aggression. This study
      analyzes the factorial structure, internal consistency, and convergent validity
      of the AQ in a Spanish sample with high levels of violence. METHOD: The
      questionnaire was administered to 767 partner-assaultive men undergoing
      psychological treatment. RESULTS: The results of the confirmatory factor analysis
      supported the four-factor structure. Also, positive correlations between the AQ
      and other instruments measuring aggression were found, finding that aggression
      and anger decrease with age in this sample. CONCLUSIONS: The results obtained
      showed that the AQ is a suitable instrument to assess aggression, anger, and
      hostility in partner-assaultive men.

PMID- 29048323
TI  - Dimensional structure and measurement invariance of the Interpersonal Reactivity
      Index (IRI) across gender.
AB  - BACKGROUND: The main goal of the present study was to examine the dimensional
      structure and measurement invariance of the Interpersonal Reactivity Index (IRI;
      Davis, 1980) across gender. METHOD: Two Spanish samples comprising 2,499 college
      students (71.2% women; M = 21.06 years) and 1,438 adults (57.8% women; M = 40.01
      years) completed the IRI. RESULTS: The study of the internal structure, using
      Exploratory Structural Equation Modeling (ESEM), revealed that the four-factor
      structure (Perspective Taking, Fantasy, Empathic Concern, and Personal Distress)
      fitted well to the college students&rsquo; data; however, in the sample of adults
      all factorial models showed modest goodness-of-fit indexes. In addition, the
      results also supported the measurement invariance of the ESEM four-factor model
      across gender in college students. Women scored higher than men in all four
      subscales of the IRI, although differences were not significant for the PT scale.
      The reliability of the scores in this sample ranged from .72 to.79. CONCLUSIONS:
      The findings support the factorial validity of the IRI scores and suggest it is a
      useful instrument to measure self-reported empathy. Future studies should
      continue to examine the structure and measurement invariance of the IRI in adult
      populations and across cultures.

PMID- 29048324
TI  - Measurement invariance of the Satisfaction With Life Scale (SWLS)by country,
      gender and age.
AB  - BACKGROUND: Although the Satisfaction With Life Scale (SWLS) is the most widely
      used instrument to measure life satisfaction with its validation having been
      carried out across ages and countries, few studies have analyzed SWLS measurement
      cross-cultural invariance with adolescents. With respect to Spanish adolescents,
      measurement invariance across gender has not been found and the one-factor
      structure has not been confirmed in Mexican adolescents through Structural
      Equation Modeling. METHOD: The main purpose of this study was to explore the
      measurement invariance of the SWLS in a sample of 701 adolescents (Mage = 14.93,
      SD = 1.83), 47.1% boys and 52.9% girls, from two different countries: Spain
      (74.2%) and Mexico (25.8%). A multigroup confirmatory factorial analysis is
      performed to test the invariance of the unifactorial structure. of SWLS with
      respect to the variables country, gender and age. RESULTS: Results support a
      single-factor structure as well as the internal consistency of the SWLS.
      Similarly, the tests of measurement invariance support its strict invariance
      regarding country and gender, and strong invariance regarding age. CONCLUSIONS:
      These results suggest that the SWLS is a useful single-factor measure of life
      satisfaction in Spanish and Mexican adolescents.

PMID- 29048325
TI  - The enigmatic xenopsins.
AB  - A new member of the family of light-sensitive proteins called opsins has stirred
      up our view of photoreceptors.

PMID- 29048326
TI  - Correction: Affective bias as a rational response to the statistics of rewards
      and punishments.

PMID- 29048327
TI  - Graphene as a thin-film catalyst booster: graphene-catalyst interface plays a
      critical role.
AB  - Due to its extreme thinness, graphene can transmit some surface properties of its
      underlying substrate, a phenomenon referred to as graphene transparency. Here we
      demonstrate the application of the transparency of graphene as a protector of
      thin-film catalysts and a booster of their catalytic efficiency. The
      photocatalytic degradation of dye molecules by ZnO thin films was chosen as a
      model system. A ZnO thin film coated with monolayer graphene showed greater
      catalytic efficiency and long-term stability than did bare ZnO. Interestingly, we
      found the catalytic efficiency of the graphene-coated ZnO thin film to depend
      critically on the nature of the bottom ZnO layer; graphene transferred to a
      relatively rough, sputter-coated ZnO thin film showed rather poor catalytic
      degradation of the dye molecules while a smooth sol-gel-synthesized ZnO covered
      with monolayer graphene showed enhanced catalytic degradation. Based on a
      systematic investigation of the interface between graphene and ZnO thin films, we
      concluded the transparency of graphene to be critically dependent on its
      interface with a supporting substrate. Graphene supported on an atomically flat
      substrate was found to efficiently transmit the properties of the substrate, but
      graphene suspended on a substrate with a rough nanoscale topography was
      completely opaque to the substrate properties. Our experimental observations
      revealed the morphology of the substrate to be a key factor affecting the
      transparency of graphene, and should be taken into account in order to optimally
      apply graphene as a protector of catalytic thin films and a booster of their
      catalysis.

PMID- 29048328
TI  - Plasmon mediated enhancement and tuning of optical emission properties of two
      dimensional graphitic carbon nitride nanosheets.
AB  - We demonstrate surface plasmon induced enhancement and tunablilty in optical
      emission properties of two dimensional graphitic carbon nitride (g-C3N4)
      nanosheets through the attachment of gold (Au) nanoparticles. Raman spectroscopy
      has revealed surface enhanced Raman scattering that arises due to the combined
      effect of the charge transfer process and localized surface plasmon induced
      enhancement in electromagnetic field, both occurring at the nanoparticle
      nanosheet interface. Photoluminescence studies suggest that at an optimal
      concentration of nanoparticles, the emission intensity can be enhanced, which is
      maximum within the 500-525 nm region. Further, the fabricated electroluminescent
      devices reveal that the emission feature can be tuned from bluish-green to red
      (~160 nm shift) upon attaching Au nanoparticles. We propose that the pi*->pi
      transition in g-C3N4 can trigger surface plasmon oscillation in Au, which
      subsequently increases the excitation process in the nanosheets and results in
      enhanced emission in the green region of the photoluminescence spectrum. On the
      other hand, electroluminescence of g-C3N4 can induce plasmon oscillation more
      efficiently and thus can lead to red emission from Au nanoparticles through the
      radiative damping of particle plasmons. The influence of nanoparticle size and
      coverage on the emission properties of two dimensional g-C3N4, nanosheets has
      also been studied in detail.

PMID- 29048329
TI  - Measurement and modeling of out-of-field doses from various advanced post
      mastectomy radiotherapy techniques.
AB  - More and more advanced radiotherapy techniques have been adopted for post
      mastectomy radiotherapies (PMRT). Patient dose reconstruction is challenging for
      these advanced techniques because they increase the low out-of-field dose area
      while the accuracy of out-of-field dose calculations by current commercial
      treatment planning systems (TPSs) is poor. We aim to measure and model the out-of
      field radiation doses from various advanced PMRT techniques. PMRT treatment plans
      for an anthropomorphic phantom were generated, including volumetric modulated arc
      therapy with standard and flattening-filter-free photon beams, mixed beam
      therapy, 4-field intensity modulated radiation therapy (IMRT), and tomotherapy.
      We measured doses in the phantom where the TPS calculated doses were lower than
      5% of the prescription dose using thermoluminescent dosimeters (TLD). The TLD
      measurements were corrected by two additional energy correction factors, namely
      out-of-beam out-of-field (OBOF) correction factor K OBOF and in-beam out-of-field
      (IBOF) correction factor K IBOF, which were determined by separate measurements
      using an ion chamber and TLD. A simple analytical model was developed to predict
      out-of-field dose as a function of distance from the field edge for each PMRT
      technique. The root mean square discrepancies between measured and calculated out
      of-field doses were within 0.66 cGy Gy-1 for all techniques. The IBOF doses were
      highly scattered and should be evaluated case by case. One can easily combine the
      measured out-of-field dose here with the in-field dose calculated by the local
      TPS to reconstruct organ doses for a specific PMRT patient if the same treatment
      apparatus and technique were used.

PMID- 29048331
TI  - Hydrogenation-driven phase transition in single-layer TiSe2.
AB  - First-principles calculations based on density-functional theory are used to
      investigate the effects of hydrogenation on the structural, vibrational, thermal
      and electronic properties of the charge density wave (CDW) phase of single-layer
      TiSe2. It is found that hydrogenation of single-layer TiSe2 is possible through
      adsorption of a H atom on each Se site. Our total energy and phonon calculations
      reveal that a structural phase transition occurs from the CDW phase to the T d
      phase upon full hydrogenation. Fully hydrogenated TiSe2 presents a direct gap
      semiconducting behavior with a band gap of 119 meV. Full hydrogenation also leads
      to a significant decrease in the heat capacity of single-layer TiSe2.

PMID- 29048330
TI  - Calibration and analysis of a multimodal micro-CT and structured light imaging
      system for the evaluation of excised breast tissue.
AB  - A multimodal micro-computed tomography (CT) and multi-spectral structured light
      imaging (SLI) system is introduced and systematically analyzed to test its
      feasibility to aid in margin delineation during breast conserving surgery (BCS).
      Phantom analysis of the micro-CT yielded a signal-to-noise ratio of 34, a
      contrast of 1.64, and a minimum detectable resolution of 240 MUm for a 1.2 min
      scan. The SLI system, spanning wavelengths 490 nm to 800 nm and spatial
      frequencies up to 1.37 [Formula: see text], was evaluated with aqueous tissue
      simulating phantoms having variations in particle size distribution, scatter
      density, and blood volume fraction. The reduced scattering coefficient, [Formula:
      see text] and phase function parameter, gamma, were accurately recovered over all
      wavelengths independent of blood volume fractions from 0% to 4%, assuming a flat
      sample geometry perpendicular to the imaging plane. The resolution of the optical
      system was tested with a step phantom, from which the modulation transfer
      function was calculated yielding a maximum resolution of 3.78 cycles per mm. The
      three dimensional spatial co-registration between the CT and optical imaging
      space was tested and shown to be accurate within 0.7 mm. A freshly resected
      breast specimen, with lobular carcinoma, fibrocystic disease, and adipose, was
      imaged with the system. The micro-CT provided visualization of the tumor mass and
      its spiculations, and SLI yielded superficial quantification of light scattering
      parameters for the malignant and benign tissue types. These results appear to be
      the first demonstration of SLI combined with standard medical tomography for
      imaging excised tumor specimens. While further investigations are needed to
      determine and test the spectral, spatial, and CT features required to classify
      tissue, this study demonstrates the ability of multimodal CT/SLI to quantify,
      visualize, and spatially navigate breast tumor specimens, which could potentially
      aid in the assessment of tumor margin status during BCS.

PMID- 29048332
TI  - One-step synthesis of NiTe2 nanorods coated with few-layers MoS2 for enhancing
      photocatalytic activity.
AB  - A facile one-step hydrothermal process was developed for fabrication of three
      dimensional hierarchical NiTe2@MoS2 heterostructures. A few layers of MoS2
      uniformly grew on the NiTe2 nanorods, possessing a higher surface area. The
      strategy was extended to CoTe2@MoS2 heterostructures with a few layers of MoS2.
      The photocatalytic activities of the heterostructures were evaluated by the
      photodegradation of methylene blue. The composites show strong adsorption ability
      and much better photocatalytic efficiency in comparison with pure MoS2
      microflowers and NiTe2 nanorods. Especially, the NiTe2@MoS2 heterostructure with
      40 wt% of MoS2 presents the highest performance in photocatalytic degradation of
      dye molecules, which is attributed to the formation of hierarchical network
      between NiTe2 nanorods and MoS2 nanosheets. And the possible mechanism of the
      enhanced photocatalytic activities was discussed.

PMID- 29048333
TI  - Quantitative analysis and predictive engineering of self-rolling of nanomembranes
      under anisotropic mismatch strain.
AB  - The present work presents a quantitative modeling framework for investigating the
      self-rolling of nanomembranes under different lattice mismatch strain anisotropy.
      The effect of transverse mismatch strain on the roll-up direction and curvature
      has been systematically studied employing both analytical modeling and numerical
      simulations. The bidirectional nature of the self-rolling of nanomembranes and
      the critical role of transverse strain in affecting the rolling behaviors have
      been demonstrated. Two fabrication strategies, i.e., third-layer deposition and
      corner geometry engineering, have been proposed to predictively manipulate the
      bidirectional rolling competition of strained nanomembranes, so as to achieve
      controlled, unidirectional roll-up. In particular for the strategy of corner
      engineering, microfabrication experiments have been performed to showcase its
      practical application and effectiveness. Our study offers new mechanistic
      knowledge towards understanding and predictive engineering of self-rolling of
      nanomembranes with improved roll-up yield.

PMID- 29048334
TI  - Predictive Parameters of Oral Health Quality of Life in Complete Mandibular
      Denture Wearers Stabilized by Mini-Implants: A Two-Year Follow-Up Study.
AB  - The frequent instability of mandibular removable complete dentures affects
      patient Oral Health Related Quality of Life (OHRQoL). An innovative therapeutic
      strategy used to improve stability involves placing four symphyseal mini
      implants. This study was aimed at assessing OHRQoL over time in subjects in which
      mini-implants were placed and exploring if certain parameters could predict the
      evolution of their OHRQoL. The OHRQoL of subjects with dentures was assessed
      using the Geriatric Oral Health Assessment Index (GOHAI) before (T0), 2-6 months
      (T1), twelve months (T2) and twenty-four or more months (T3) after mini-implant
      setting. Age, gender and chewing ability were tested as explanatory variables for
      the change in OHRQoL with time. Thirteen women and six men were included (mean
      age: 69 +/- 10 years). After treatment, mean GOHAI scores at T1, T2 and T3
      increased significantly (p < 0.001). The GOHAI-Add mean score was not affected by
      age or gender. Baseline chewing ability impacted the "functional" and "pain and
      discomfort" fields of the mean GOHAI scores (p < 0.05). The OHRQoL quickly
      improved after mini-implant placement in complete denture wearers and then
      stabilized over time. Baseline chewing ability can be used as a predictive
      parameter of OHRQoL.

PMID- 29048336
TI  - Proanthocyanidin Characterization, Antioxidant and Cytotoxic Activities of Three
      Plants Commonly Used in Traditional Medicine in Costa Rica: Petiveria alliaceae
      L., Phyllanthus niruri L. and Senna reticulata Willd.
AB  - The phenolic composition of aerial parts from Petiveria alliaceae L., Phyllanthus
      niruri L. and Senna reticulata Willd., species commonly used in Costa Rica as
      traditional medicines, was studied using UPLC-ESI-TQ-MS on enriched-phenolic
      extracts. Comparatively, higher values of total phenolic content (TPC), as
      measured by the Folin-Ciocalteau method, were observed for P. niruri extracts
      (328.8 gallic acid equivalents/g) than for S. reticulata (79.30 gallic acid
      equivalents/g) whereas P. alliaceae extract showed the lowest value (13.45 gallic
      acid equivalents/g). A total of 20 phenolic acids and proanthocyanidins were
      identified in the extracts, including hydroxybenzoic acids (benzoic, 4
      hydroxybenzoic, gallic, prochatechuic, salicylic, syringic and vanillic acids);
      hydroxycinnamic acids (caffeic, ferulic, and p-coumaric acids); and flavan-3-ols
      monomers [(+)-catechin and (-)-epicatechin)]. Regarding proanthocyanidin
      oligomers, five procyanidin dimers (B1, B2, B3, B4, and B5) and one trimer (T2)
      are reported for the first time in P. niruri, as well as two propelargonidin
      dimers in S. reticulata. Additionally, P. niruri showed the highest antioxidant
      DPPH and ORAC values (IC50 of 6.4 MUg/mL and 6.5 mmol TE/g respectively),
      followed by S. reticulata (IC50 of 72.9 MUg/mL and 2.68 mmol TE/g respectively)
      and P. alliaceae extract (IC50 >1000 MUg/mL and 1.32 mmol TE/g respectively).
      Finally, cytotoxicity and selectivity on gastric AGS and colon SW20
      adenocarcinoma cell lines were evaluated and the best values were also found for
      P. niruri (SI = 2.8), followed by S. reticulata (SI = 2.5). Therefore, these
      results suggest that extracts containing higher proanthocyanidin content also
      show higher bioactivities. Significant positive correlation was found between TPC
      and ORAC (R2 = 0.996) as well as between phenolic content as measured by UPLC-DAD
      and ORAC (R2 = 0.990). These findings show evidence for the first time of the
      diversity of phenolic acids in P. alliaceae and S. reticulata, and the presence
      of proanthocyanidins as minor components in latter species. Of particular
      relevance is the occurrence of proanthocyanidin oligomers in phenolic extracts
      from P. niruri and their potential bioactivity.

PMID- 29048335
TI  - Bone Marrow-Derived Stem Cell Populations Are Differentially Regulated by Thyroid
      or/and Ovarian Hormone Loss.
AB  - Bone marrow-derived stem cells (BMDSCs) play an essential role in organ repair
      and regeneration. The molecular mechanisms by which hormones control BMDSCs
      proliferation and differentiation are unclear. Our aim in this study was to
      investigate how a lack of ovarian or/and thyroid hormones affects stem cell
      number in bone marrow lineage. To examine the effect of thyroid or/and ovarian
      hormones on the proliferative activity of BMDSCs, we removed the thyroid or/and
      the ovaries of adult female rats. An absence of ovarian and thyroid hormones was
      confirmed by Pap staining and Thyroid Stimulating Hormone (TSH) measurement,
      respectively. To obtain the stem cells from the bone marrow, we punctured the
      iliac crest, and aspirated and isolated cells by using a density gradient.
      Specific markers were used by cytometry to identify the different BMDSCs types:
      endothelial progenitor cells (EPCs), precursor B cells/pro-B cells, and
      mesenchymal stem cells (MSCs). Interestingly, our results showed that
      hypothyroidism caused a significant increase in the percentage of EPCs, whereas a
      lack of ovarian hormones significantly increased the precursor B cells/pro-B
      cells. Moreover, the removal of both glands led to increased MSCs. In conclusion,
      both ovarian and thyroid hormones appear to have key and diverse roles in
      regulating the proliferation of cells populations of the bone marrow.

PMID- 29048337
TI  - Paid Sick Leave and Risks of All-Cause and Cause-Specific Mortality among Adult
      Workers in the USA.
AB  - Background: The USA is one of only a few advanced economies globally that does
      not guarantee its workers paid sick leave. While there are plausible reasons why
      paid sick leave may be linked to mortality, little is known empirically about
      this association. Methods: In a pooled USA nationally-representative longitudinal
      sample of 57,323 working adults aged 18-85 years from the National Health
      Interview Surveys 2000-2002, paid sick leave was examined as a predictor of all
      cause and cause-specific mortality. Multivariate Cox proportional hazards models
      were used to estimate the impact of paid sick leave on mortality. Results: Having
      paid sick leave through one's job was associated with 10% (hazards ratio, HR =
      0.90; 95% CI = 0.81-0.996; p = 0.04), 14% (HR = 0.86; 95% CI = 0.74-0.99; p =
      0.04), and 22% (HR = 0.78; 95% CI = 0.65-0.94; p = 0.01) significantly lower
      hazards of all-cause mortality after mean follow-up times of 11.1, 6.5, and 4.5
      years, respectively. This study further identified associations of paid sick
      leave with 24% (HR = 0.76; 95% CI = 0.59-0.98; p = 0.03), and 35% (HR = 0.65; 95%
      CI = 0.44-0.95; p = 0.03) lower hazards of dying from heart diseases and
      unintentional injuries, respectively. Conclusions: To the author's knowledge,
      this study provides the first empirical evidence on the linkages between paid
      sick leave and mortality and supports protective effects, particularly against
      heart diseases and unintentional injuries. The most salient association
      corresponded to a lag period of just less than five years. Social policies that
      mandate paid sick leave may help to reduce health inequities and alleviate the
      population burden of mortality among working adults in the USA.

PMID- 29048338
TI  - G-Protein Dependent Signal Transduction and Ubiquitination in Dictyostelium.
AB  - Signal transduction through G-protein-coupled receptors (GPCRs) is central for
      the regulation of virtually all cellular functions, and it has been widely
      implicated in human diseases. These receptors activate a common molecular switch
      that is represented by the heterotrimeric G-protein generating a number of second
      messengers (cAMP, cGMP, DAG, IP3, Ca2+ etc.), leading to a plethora of diverse
      cellular responses. Spatiotemporal regulation of signals generated by a given
      GPCR is crucial for proper signalling and is accomplished by a series of
      biochemical modifications. Over the past few years, it has become evident that
      many signalling proteins also undergo ubiquitination, a posttranslational
      modification that typically leads to protein degradation, but also mediates
      processes such as protein-protein interaction and protein subcellular
      localization. The social amoeba Dictyostelium discoideum has proven to be an
      excellent model to investigate signal transduction triggered by GPCR activation,
      as cAMP signalling via GPCR is a major regulator of chemotaxis, cell
      differentiation, and multicellular morphogenesis. Ubiquitin ligases have been
      recently involved in these processes. In the present review, we will summarize
      the most significant pathways activated upon GPCRs stimulation and discuss the
      role played by ubiquitination in Dictyostelium cells.

PMID- 29048340
TI  - Helping Health Services to Meet the Needs of Young People with Chronic
      Conditions: Towards a Developmental Model for Transition.
AB  - The transition to adult healthcare has been the subject of increased research and
      policy attention over many years. However, unmet needs of adolescent and young
      adults (AYAs) and their families continue to be documented, and universal
      implementation has yet to be realised. Therefore, it is pertinent to re-examine
      health transition in light of the principles of adolescent medicine from which it
      emerged, and consider this particular life transition in terms of a developmental
      milestone rather than a negotiation of structural boundaries between child and
      adult services. Health transitions are an integral part of AYA development and as
      such, occur alongside, and in connection with, a range of other important
      transitions that affect many other areas of life. In this paper, we discuss the
      interrelated nature of health transitions and AYA development; outline the
      underpinnings of a developmentally appropriate approach to transitional care; and
      consider the outcome measurement of such care based on existing evidence. A
      developmental approach has the potential to refocus transition on the fundamental
      principles of adolescent medicine, enabling health transition to be integrated
      along with other life transitions into routine AYA developmental assessments
      rather than being limited to the geographies of different healthcare settings and
      a potential health crisis.

PMID- 29048341
TI  - Modified Gray-Level Coding Method for Absolute Phase Retrieval.
AB  - Fringe projection systems have been widely applied in three-dimensional (3D)
      shape measurements. One of the important issues is how to retrieve the absolute
      phase. This paper presents a modified gray-level coding method for absolute phase
      retrieval. Specifically, two groups of fringe patterns are projected onto the
      measured objects, including three phase-shift patterns for the wrapped phase, and
      three n-ary gray-level (nGL) patterns for the fringe order. Compared with the
      binary gray-level (bGL) method which just uses two intensity values, the nGL
      method can generate many more unique codewords with multiple intensity values.
      With assistance from the average intensity and modulation of phase-shift
      patterns, the intensities of nGL patterns are normalized to deal with ambient
      light and surface contrast. To reduce the codeword detection errors caused by
      camera/projector defocus, nGL patterns are designed as n-ary gray-code (nGC)
      patterns to ensure that at most, one code changes at each point. Experiments
      verify the robustness and effectiveness of the proposed method to measure
      isolated objects with complex surfaces.

PMID- 29048339
TI  - Understanding the Contribution of Zinc Transporters in the Function of the Early
      Secretory Pathway.
AB  - More than one-third of newly synthesized proteins are targeted to the early
      secretory pathway, which is comprised of the endoplasmic reticulum (ER), Golgi
      apparatus, and other intermediate compartments. The early secretory pathway plays
      a key role in controlling the folding, assembly, maturation, modification,
      trafficking, and degradation of such proteins. A considerable proportion of the
      secretome requires zinc as an essential factor for its structural and catalytic
      functions, and recent findings reveal that zinc plays a pivotal role in the
      function of the early secretory pathway. Hence, a disruption of zinc homeostasis
      and metabolism involving the early secretory pathway will lead to pathway
      dysregulation, resulting in various defects, including an exacerbation of
      homeostatic ER stress. The accumulated evidence indicates that specific members
      of the family of Zn transporters (ZNTs) and Zrt- and Irt-like proteins (ZIPs),
      which operate in the early secretory pathway, play indispensable roles in
      maintaining zinc homeostasis by regulating the influx and efflux of zinc. In this
      review, the biological functions of these transporters are discussed, focusing on
      recent aspects of their roles. In particular, we discuss in depth how specific
      ZNT transporters are employed in the activation of zinc-requiring ectoenzymes.
      The means by which early secretory pathway functions are controlled by zinc,
      mediated by specific ZNT and ZIP transporters, are also subjects of this review.

PMID- 29048342
TI  - Optical Sensing of Weed Infestations at Harvest.
AB  - Kochia (Kochia scoparia L.), Russian thistle (Salsolatragus L.), and prickly
      lettuce (Lactuca serriola L.) are economically important weeds infesting dryland
      wheat (Triticum aestivum L.) production systems in the western United States.
      Those weeds produce most of their seeds post-harvest. The objectives of this
      study were to determine the ability of an optical sensor, installed for on-the-go
      measurement of grain protein concentration, to detect the presence of green plant
      matter in flowing grain and assess the potential usefulness of this information
      for mapping weeds at harvest. Spectra of the grain stream were recorded
      continuously at a rate of 0.33 Hz during harvest of two spring wheat fields of
      1.9 and 5.4 ha. All readings were georeferenced using a Global Positioning System
      (GPS) receiver with 1 m positional accuracy. Chlorophyll of green plant matter
      was detectable in the red (638-710 nm) waveband. Maps of the chlorophyll signal
      from both fields showed an overall agreement of 78.1% with reference maps, one
      constructed prior to harvest and the other at harvest time, both based on visual
      evaluations of the three green weed species conducted by experts. Information on
      weed distributions at harvest may be useful for controlling post-harvest using
      variable rate technology for herbicide applications.

PMID- 29048343
TI  - A Practical Example of GaN-LED Failure Cause Analysis by Application of Combined
      Electron Microscopy Techniques.
AB  - In this paper, we report a failure case of blue LEDs returned from a field
      application, and propose a practical way to identify the physical and structural
      reasons for the observed malfunction by a combination of different electron
      microscope techniques. Cathodoluminescence imaging and electron beam induced
      current (EBIC) imaging are employed in order to visualize conductive paths
      through the device in conjunction with subsequent energy dispersive x-ray
      analysis (EDS), revealing a metal deposition along cracks in the semiconductor
      layer which short-circuit the device. We demonstrate that the electron beam
      induced current imaging, in conjunction with other microscopic and analytical
      techniques at um scale, is a powerful combination for clearly resolving and
      visualizing the cause of failure in the GaN LED chip. However, this represents a
      case study of a real application, which may not have been generally observed in
      laboratory testing environment.

PMID- 29048344
TI  - Influence of Ultrasonic Surface Rolling on Microstructure and Wear Behavior of
      Selective Laser Melted Ti-6Al-4V Alloy.
AB  - The present article studied the effect of ultrasonic surface rolling process
      (USRP) on the microstructure and wear behavior of a selective laser melted Ti-6Al
      4V alloy. Surface characteristics were investigated using optical microscope,
      nano-indentation, scanning electron microscope, transmission electron microscope
      and laser scanning confocal microscope. Results indicated that the thickness of
      pore-free surfaces increased to 100~200 MUm with the increasing ultrasonic
      surface rolling numbers. Severe work hardening occurred in the densified layer,
      resulting in the formation of refined grains, dislocation walls and deformation
      twins. After 1000 N 6 passes, about 15.5% and 14.1% increment in surficial Nano
      hardness and Vickers-hardness was obtained, respectively. The hardness decreased
      gradually from the top surface to the substrate. Wear tests revealed that the
      friction coefficient declined from 0.74 (polished surface) to 0.64 (USRP treated
      surface) and the wear volume reduced from 0.205 mm-3 to 0.195 mm-3. The
      difference in wear volume between USRP treated and polished samples increased
      with sliding time. The enhanced wear resistance was concluded to be associated
      with the improvement of hardness and shear resistance and also the inhibition of
      delamination initiation.

PMID- 29048345
TI  - Enhancement of Fracture Toughness of Epoxy Nanocomposites by Combining Nanotubes
      and Nanosheets as Fillers.
AB  - In this work the fracture toughness of epoxy resin has been improved through the
      addition of low loading of single part and hybrid nanofiller materials.
      Functionalised multi-walled carbon nanotubes (f-MWCNTs) was used as single
      filler, increased the critical strain energy release rate, GIC, by 57% compared
      to the neat epoxy, at only 0.1 wt% filler content. Importantly, no degradation in
      the tensile or thermal properties of the nanocomposite was observed compared to
      the neat epoxy. When two-dimensional boron nitride nanosheets (BNNS) were added
      along with the one-dimensional f-MWCNTs, the fracture toughness increased further
      to 71.6% higher than that of the neat epoxy. Interestingly, when functionalised
      graphene nanoplatelets (f-GNPs) and boron nitride nanotubes (BNNTs) were used as
      hybrid filler, the fracture toughness of neat epoxy is improved by 91.9%. In
      neither of these hybrid filler systems the tensile properties were degraded, but
      the thermal properties of the nanocomposites containing boron nitride materials
      deteriorated slightly.

PMID- 29048346
TI  - Finite Element Modeling of Tensile Deformation Behaviors of Iron Syntactic Foam
      with Hollow Glass Microspheres.
AB  - The elastoplastic deformation behaviors of hollow glass microspheres/iron
      syntactic foam under tension were modeled using a representative volume element
      (RVE) approach. The three-dimensional microstructures of the iron syntactic foam
      with 5 wt % glass microspheres were reconstructed using the random sequential
      adsorption algorithm. The constitutive behavior of the elastoplasticity in the
      iron matrix and the elastic-brittle failure for the glass microsphere were
      simulated in the models. An appropriate RVE size was statistically determined by
      evaluating elastic modulus, Poisson's ratio, and yield strength in terms of model
      sizes and boundary conditions. The model was validated by the agreement with
      experimental findings. The tensile deformation mechanism of the syntactic foam
      considering the fracture of the microspheres was then investigated. In addition,
      the feasibility of introducing the interfacial deboning behavior to the proposed
      model was briefly investigated to improve the accuracy in depicting fracture
      behaviors of the syntactic foam. It is thought that the modeling techniques and
      the model itself have major potential for applications not only in the study of
      hollow glass microspheres/iron syntactic foams, but also for the design of
      composites with a high modulus matrix and high strength reinforcement.

PMID- 29048347
TI  - Three-Dimensional (3D) Printing of Polymer-Metal Hybrid Materials by Fused
      Deposition Modeling.
AB  - Fused deposition modeling (FDM) is a three-dimensional (3D) printing technology
      that is usually performed with polymers that are molten in a printer nozzle and
      placed line by line on the printing bed or the previous layer, respectively.
      Nowadays, hybrid materials combining polymers with functional materials are also
      commercially available. Especially combinations of polymers with metal particles
      result in printed objects with interesting optical and mechanical properties. The
      mechanical properties of objects printed with two of these metal-polymer blends
      were compared to common poly (lactide acid) (PLA) printed objects. Tensile tests
      and bending tests show that hybrid materials mostly containing bronze have
      significantly reduced mechanical properties. Tensile strengths of the 3D-printed
      objects were unexpectedly nearly identical with those of the original filaments,
      indicating sufficient quality of the printing process. Our investigations show
      that while FDM printing allows for producing objects with mechanical properties
      similar to the original materials, metal-polymer blends cannot be used for the
      rapid manufacturing of objects necessitating mechanical strength.

PMID- 29048348
TI  - Analysis of a Community Pharmacy Intervention to Improve Low Adherence Rates to
      Oral Diabetes Medications.
AB  - For patients with diabetes, suboptimal medication adherence contributes to
      disease progression, complications, and increased healthcare costs.
      Identification of, and intervention for patient-identified reasons for
      nonadherence are essential to improving medication adherence. This prospective,
      quality improvement study was conducted at an independent community pharmacy in
      the Mid-West United States. Patients with a proportion of days covered (PDC) for
      their oral antidiabetic medications of less than 80% were contacted by telephone
      and interviewed by a clinical pharmacist. The interviews and corresponding
      adherence interventions were guided by an abbreviated version of the Drug
      Adherence Work-Up (DRAW(c)) tool that focused on oral medications for diabetes.
      The change in PDC 120-days post-interview was assessed to determine the change in
      adherence rates. Patients receiving the pharmacist-delivered adherence
      intervention had significantly higher 120 day PDC values which are likely to
      indicate more regular medication-taking at home. Almost half of study patients
      signed up for medication synchronization and these patients trended toward higher
      PDC values, although the relative difference was not statistically significant
      from those receiving the intervention and not opting to have their medications
      synchronized.

PMID- 29048349
TI  - Raman Enhancement and Photo-Bleaching of Organic Dyes in the Presence of Chemical
      Vapor Deposition-Grown Graphene.
AB  - Fluorescent organic dyes photobleach under intense light. Graphene has been shown
      to improve the photo-stability of organic dyes. In this paper, we investigated
      the Raman spectroscopy and photo-bleaching kinetics of dyes in the
      absence/presence of chemical vapor deposition (CVD)-grown graphene. We show that
      graphene enhances the Raman signal of a wide range of dyes. The photo-bleaching
      of the dyes was reduced when the dyes were in contact with graphene. In contrast,
      monolayer hexagonal boron nitride (h-BN) was much less effective in reducing the
      photo-bleaching rate of the dyes. We attribute the suppression of photo-bleaching
      to the energy or electron transfer from dye to graphene. The results highlight
      the potential of CVD graphene as a substrate for protecting and enhancing Raman
      response of organic dyes.

PMID- 29048350
TI  - WHO Environmental Noise Guidelines for the European Region: A Systematic Review
      on Environmental Noise and Adverse Birth Outcomes.
AB  - : Introduction: Three recent systematic reviews suggested a relationship between
      noise exposure and adverse birth outcomes. The aim of this review was to evaluate
      the evidence for the World Health Organization (WHO) noise guidelines and conduct
      an updated systematic review of environmental noise, specifically aircraft and
      road traffic noise and birth outcomes, such as preterm birth, low birth weight,
      being small for gestational age and congenital malformations. Materials and
      methods: We reviewed again all the papers on environmental noise and birth
      outcomes included in the previous three systematic reviews and conducted a
      systematic search on noise and birth outcomes to update previous reviews. Web of
      Science, PubMed and Embase electronic databases were searched for papers
      published between June 2014 (end date of previous systematic review) and December
      2016 using a list of specific search terms. Studies were also screened in the
      reference list of relevant reviews/articles. Further inclusion and exclusion
      criteria for the studies provided by the WHO expert group were applied. Risk of
      bias was assessed according to criteria from the Newcastle-Ottawa quality
      assessment scale for case-control and cohort studies. Finally, we applied the
      GRADE principles to our systematic review in a reproducible and appropriate way
      for judgment about quality of evidence. Results: In total, 14 studies are
      included in this review, six studies on aircraft noise and birth outcomes, five
      studies (two with more or less the same population) on road traffic noise and
      birth outcomes and three related studies on total ambient noise that is likely to
      be mostly traffic noise that met the criteria. The number of studies on
      environmental noise and birth outcomes is small and the quality of evidence
      generally ranges from very low to low, particularly in case of the older studies.
      The quality is better for the more recent traffic noise and birth outcomes
      studies. As there were too few studies, we did not conduct meta-analyses.
      Discussion: This systematic review is supported by previous systematic reviews
      and meta-analyses that suggested that there may be some suggestive evidence for
      an association between environmental noise exposure and birth outcomes, although
      they pointed more generally to a stronger role of occupational noise exposure,
      which tends to be higher and last longer. Very strict criteria for inclusion and
      exclusion of studies, performance of quality assessment for risk of bias, and
      finally applying GRADE principles for judgment of quality of evidence are the
      strengths of this review. CONCLUSIONS: We found evidence of very low quality for
      associations between aircraft noise and preterm birth, low birth weight and
      congenital anomalies, and low quality evidence for an association between road
      traffic noise and low birth weight, preterm birth and small for gestational age.
      Further high quality studies are required to establish such associations. Future
      studies are recommended to apply robust exposure assessment methods (e.g.,
      modeled or measured noise levels at bedroom facade), disentangle associations for
      different sources of noise as well as daytime and nighttime noise, evaluate the
      impacts of noise evens (that stand out of the noise background), and control the
      analyses for confounding factors, such as socioeconomic status, lifestyle factors
      and other environmental factors, especially air pollution.

PMID- 29048351
TI  - Bacterial Substrate Transformation Tracked by Stable-Isotope-Guided NMR
      Metabolomics: Application in a Natural Aquatic Microbial Community.
AB  - The transformation of organic substrates by heterotrophic bacteria in aquatic
      environments constitutes one of the key processes in global material cycles. The
      development of procedures that would enable us to track the wide range of organic
      compounds transformed by aquatic bacteria would greatly improve our understanding
      of material cycles. In this study, we examined the applicability of nuclear
      magnetic resonance spectroscopy coupled with stable-isotope labeling to the
      investigation of metabolite transformation in a natural aquatic bacterial
      community. The addition of a model substrate (13C6-glucose) to a coastal seawater
      sample and subsequent incubation resulted in the detection of >200 peaks and the
      assignment of 22 metabolites from various chemical classes, including amino
      acids, dipeptides, organic acids, nucleosides, nucleobases, and amino alcohols,
      which had been identified as transformed from the 13C6-glucose. Additional
      experiments revealed large variability in metabolite transformation and the key
      compounds, showing the bacterial accumulation of glutamate over the incubation
      period, and that of 3-hydroxybutyrate with increasing concentrations of 13C6
      glucose added. These results suggest the potential ability of our approach to
      track substrate transformation in aquatic bacterial communities. Further
      applications of this procedure may provide substantial insights into the
      metabolite dynamics in aquatic environments.

PMID- 29048352
TI  - Effects of Short-Term Probiotic Ingestion on Immune Profiles and Microbial
      Translocation among HIV-1-Infected Vietnamese Children.
AB  - Here, we investigated the effects of the probiotic strain Lactobacillus casei
      Shirota (LcS) on immune profiles and intestinal microbial translocation among
      children infected with human immunodeficiency virus (HIV). This prospective study
      included 60 HIV-infected children-including 31 without antiretroviral therapy
      (ART) (HIV(+)) and 29 who received ART for a median of 3.5 years (ART(+)) and 20
      children without HIV infection (HIV(-)). Participants were recruited in Vietnam.
      All children were given fermented milk containing LcS (6.5 * 108 cfu) daily for 8
      weeks. Before and after LcS ingestion, blood samples were collected for
      virological, immunological, and bacteriological analyses. After LcS ingestion,
      peripheral CD4+ T-cell and Th2 (CXCR3-CCR6-CD4+) counts significantly increased
      in both HIV-infected groups; Th17 (CXCR3-CCR6+CD4+) counts increased in all three
      groups; regulatory T-cell (CD25highCD4+) counts decreased in the ART(+) and HIV(
      ) groups; activated CD8+ cells (CD38+HLA-DR+CD8+) decreased from 27.5% to 13.2%
      (p < 0.001) in HIV(+) children; and plasma HIV load decreased slightly but
      significantly among HIV(+) children. No group showed a significantly altered
      frequency of bacterial 16S/23S rRNA gene detection in the plasma. No serious
      adverse events occurred. These findings suggest that short-term LcS ingestion is
      a safe supportive approach with immunological and virological benefits in HIV
      infected children.

PMID- 29048353
TI  - P2X-Receptor Antagonists Inhibit the Interaction of S. aureus Hemolysin A with
      Membranes.
AB  - The pore forming hemolysin A, Hla, is a major virulence factor of Staphylococcus
      aureus. Apparently, 1-2 pore(s) per cell suffice(s) to cause cell death.
      Accumulated experimental evidence points towards a major role of ATP-gated
      purinergic receptors (P2XR) for hemolysis caused by Hla, complement and other
      pore forming proteins, presumably by increasing membrane permeability. Indeed, in
      experiments employing rabbit erythrocytes, inhibitory concentrations of
      frequently employed P2XR-antagonists were in a similar range as previously
      reported for erythrocytes of other species and other toxins. However, Hla
      dependent hemolysis was not enhanced by extracellular ATP, and oxidized
      adenosinetriphosphate (oxATP) had only a minor inhibitory effect. Unexpectedly,
      P2XR-inhibitors also prevented Hla-induced lysis of pure lipid membranes,
      demonstrating that the inhibition did not even depend on the presence of P2XR.
      Fluorescence microscopy and gel-electrophoresis clearly revealed that P2XR
      inhibitors interfere with binding and subsequent oligomerisation of Hla with
      membranes. Similar results were obtained employing HaCaT-cells. Furthermore,
      calorimetric data and hemolysis experiments with Hla pre-treated with pyridoxal
      phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) showed that this compound
      directly binds to Hla. Our results call for a critical re-assessment of the
      appealing concept, which suggests that P2XR are general amplifiers of damage by
      pore-forming proteins.

PMID- 29048355
TI  - Factors Associated with Malnutrition among Under-Five Children: Illustration
      using Bangladesh Demographic and Health Survey, 2014 Data.
AB  - Child malnutrition remains one of the major public health problems in many parts
      of the world, especially in a developing country like Bangladesh. Several
      socioeconomic and demographic factors are responsible for this condition. The
      present study was conducted to uncover the risk factors associated with
      malnutrition among under-five children in Bangladesh by analyzing the data from a
      nationally representative Bangladesh Demographic and Health Survey (BDHS) in
      2014. The ordinal dependent variable-child nutrition status (severely
      malnourished, moderately malnourished, and nourished)-was developed by
      calculating weight-for-age Z score (WAZ). Bivariate analysis was conducted by
      performing gamma measure and chi-square test of independence to explore the
      association between child nutrition status and selected independent variables. To
      know the adjusted effects of covariates, a popular ordinal model-namely, the
      proportional odds (PO) model-was considered. All the selected covariates were
      found highly significant (p < 0.01) in the bivariate setup. However, in the
      multivariate setup, father's and mother's education, wealth index, mother's body
      mass index (BMI), and antenatal care service during pregnancy were found highly
      significant (p < 0.01) factors for child malnutrition. Among the divisions, only
      Dhaka had more control on child malnutrition, compared to the Sylhet division.
      Birth interval of children was also reported as a significant factor at a 5%
      level of significance. Finally, the results of this paper strongly highlighted
      the necessity of increasing parent's education level, improving the mother's
      nutritional status, and increasing facilities providing antenatal care service in
      order to achieve better nutrition status among under-five children in Bangladesh.

PMID- 29048356
TI  - Mycotoxin Analysis of Human Urine by LC-MS/MS: A Comparative Extraction Study.
AB  - The lower mycotoxin levels detected in urine make the development of sensitive
      and accurate analytical methods essential. Three extraction methods, namely
      salting-out liquid-liquid extraction (SALLE), miniQuEChERS (quick, easy, cheap,
      effective, rugged, and safe), and dispersive liquid-liquid microextraction
      (DLLME), were evaluated and compared based on analytical parameters for the
      quantitative LC-MS/MS measurement of 11 mycotoxins (AFB1, AFB2, AFG1, AFG2, OTA,
      ZEA, BEA, EN A, EN B, EN A1 and EN B1) in human urine. DLLME was selected as the
      most appropriate methodology, as it produced better validation results for
      recovery (79-113%), reproducibility (RSDs < 12%), and repeatability (RSDs < 15%)
      than miniQuEChERS (71-109%, RSDs <14% and <24%, respectively) and SALLE (70-108%,
      RSDs < 14% and < 24%, respectively). Moreover, the lowest detection (LODS) and
      quantitation limits (LOQS) were achieved with DLLME (LODs: 0.005-2 MUg L-1, LOQs:
      0.1-4 MUg L-1). DLLME methodology was used for the analysis of 10 real urine
      samples from healthy volunteers showing the presence of ENs B, B1 and A1 at low
      concentrations.

PMID- 29048357
TI  - Health Philosophy of Dietitians and Its Implications for Life Satisfaction: An
      Exploratory Study.
AB  - Studies of health providers suggest that satisfaction with life is related to
      their values and sense of purpose which is best achieved when their professional
      role is in harmony with personal philosophy. Cross-sectional surveys suggest that
      personal health beliefs and practices of health professionals influence their
      clinical counseling practices. However, little is known about the influence of
      health philosophy on the personal satisfaction with life for dietitians. This
      study recruited a randomly selected, cross-sectional sample to complete a self
      administered online survey. An exploratory factor analysis of was conducted for
      479 participants resulting in a two-factor solution, clinical (alpha = 0.914) and
      wellness (alpha = 0.894) perceptions of health. An index score for the following
      valid and reliable scales were calculated: satisfaction with life, health
      conception, and healthy lifestyle and personal control. Pearson correlation
      coefficients between scores were analyzed to determine the degree of
      relationship. Potential mediators were explored with multiple regression. The
      relationships between variables were tested with structural equation modeling
      using a multigroup comparison between genders. The male participants were removed
      from the overall model and were separately evaluated. Health philosophy that is
      oriented toward wellness, was positively and significantly associated with life
      satisfaction, r(462) = 0.103, p < 0.05. Participants with higher Healthy
      Lifestyle and Personal Control scores reported greater life satisfaction, r(462)
      = 0.27, p = 0.000. Healthy lifestyle alone predicted 8.8% of the variance in life
      satisfaction (R2 = 0.088, df 1462, p = 0.005). SEM confirmed the model had
      goodness-of-fit (chi2 = 2.63, p = 0.453). The satisfaction with life of
      dietitians is directly and positively influenced by a greater wellness
      orientation and personal healthy lifestyle practices. The effect of practice and
      lifestyle on life satisfaction appears to be greater for men.

PMID- 29048354
TI  - Hepatitis B Virus and DNA Damage Response: Interactions and Consequences for the
      Infection.
AB  - Hepatitis B virus (HBV) is a major etiologic agent of acute and chronic
      hepatitis, and end-stage liver disease. Establishment of HBV infection,
      progression to persistency and pathogenesis are determined by viral and cellular
      factors, some of which remain still undefined. Key steps of HBV life cycle e.g.,
      transformation of genomic viral DNA into transcriptionally active episomal DNA
      (cccDNA) or transcription of viral mRNAs from cccDNA, take place in the nucleus
      of infected cells and strongly depend on enzymatic activities provided by
      cellular proteins. In this regard, DNA damage response (DDR) pathways and some
      DDR proteins are being recognized as important factors regulating the infection.
      On one hand, HBV highjacks specific DDR proteins to successfully complete some of
      the steps of its life cycle. On the other hand, HBV subverts DDR pathways to
      presumably create a cellular environment that favours its replication. Direct
      consequences of these interactions are: HBV DNA integration into host chromosomal
      DNA, and accumulation of mutations in host chromosomal DNA that could eventually
      trigger carcinogenic processes, which would explain in part the incidence of
      hepatocellular carcinoma in chronically infected patients. Unravelling the
      interactions that HBV establishes with DDR pathways might help identify new
      molecular targets for therapeutic intervention.

PMID- 29048358
TI  - Alleviate Similar Object in Visual Tracking via Online Learning Interference
      Target Spatial Structure.
AB  - Correlation Filter (CF) based trackers have demonstrated superior performance to
      many complex scenes in smart and autonomous systems, but similar object
      interference is still a challenge. When the target is occluded by a similar
      object, they not only have similar appearance feature but also are in same
      surrounding context. Existing CF tracking models only consider the target's
      appearance information and its surrounding context, and have insufficient
      discrimination to address the problem. We propose an approach that integrates
      interference-target spatial structure (ITSS) constraints into existing CF model
      to alleviate similar object interference. Our approach manages a dynamic graph of
      ITSS online, and jointly learns the target appearance model, similar object
      appearance model and the spatial structure between them to improve the
      discrimination between the target and a similar object. Experimental results on
      large benchmark datasets OTB-2013 and OTB-2015 show that the proposed approach
      achieves state-of-the-art performance.

PMID- 29048359
TI  - Chitosan Ascorbate Nanoparticles for the Vaginal Delivery of Antibiotic Drugs in
      Atrophic Vaginitis.
AB  - The aim of the present work was the development of chitosan ascorbate
      nanoparticles (CSA NPs) loaded into a fast-dissolving matrix for the delivery of
      antibiotic drugs in the treatment of atrophic vaginitis. CSA NPs loaded with
      amoxicillin trihydrate (AX) were obtained by ionotropic gelation in the presence
      of pentasodium tripolyphosphate (TPP). Different CSA:TPP and CSA:AX weight ratios
      were considered and their influence on the particle size, polydispersion index
      and production yield were investigated. CSA NPs were characterized for
      mucoadhesive, wound healing and antimicrobial properties. Subsequently, CSA NPs
      were loaded in polymeric matrices, whose composition was optimized using a DoE
      (Design of Experiments) approach (simplex centroid design). Matrices were
      obtained by freeze-drying aqueous solutions of three hydrophilic excipients,
      polyvinylpirrolidone, mannitol and glycin. They should possess a mechanical
      resistance suitable for the administration into the vaginal cavity and should
      readily dissolve in the vaginal fluid. In addition to antioxidant properties, due
      to the presence of ascorbic acid, CSA NPs showed in vitro mucoadhesive, wound
      healing and antimicrobial properties. In particular, nanoparticles were
      characterized by an improved antimicrobial activity with respect to a chitosan
      solution, prepared at the same concentration. The optimized matrix was
      characterized by mechanical resistance and by the fast release in simulated
      vaginal fluid of nanoparticles characterized by unchanged size.

PMID- 29048360
TI  - Graded Microstructure and Mechanical Performance of Ti/N-Implanted M50 Steel with
      Polyenergy.
AB  - M50 bearing steels were alternately implanted with Ti+ and N+ ions using solid
      and gas ion sources of implantation system, respectively. N-implantation was
      carried out at an energy of about 80 keV and a fluence of 2 * 1017 ions/cm2, and
      Ti-implantation at an energy of about 40-90 keV and a fluence of 2 * 1017
      ions/cm2. The microstructures of modification layers were analyzed by grazing
      incidence X-ray diffraction, auger electron spectroscopy, X-ray photoelectron
      spectroscopy, and transmission electron microscopy. The results showed that the
      gradient structure was formed under the M50 bearing steel subsurface, along the
      ion implantation influence zone composed of amorphous, nanocrystalline, and
      gradient-refinement phases. A layer of precipitation compounds like TiN is
      formed. In addition, nano-indentation hardness and tribological properties of the
      gradient structure subsurface were examined using a nano-indenter and a friction
      and wear tester. The nano-indentation hardness of N + Ti-co-implanted sample is
      above 12 GPa, ~1.3 times than that of pristine samples. The friction coefficient
      is smaller than 0.2, which is 22.2% of that of pristine samples. The synergism
      between precipitation-phase strengthening and gradient microstructure is the main
      mechanism for improving the mechanical properties of M50 materials.

PMID- 29048362
TI  - Report from the BIT's 4th Annual World Congress of High-Tech Acupuncture and
      Integrative Medicine Held in Xi'an, China, 25-27 September 2017.
AB  - High-tech acupuncture is an example of a very successful cross-over between
      tradition and innovation. "The Annual World Congress of High-Tech Acupuncture and
      Integrative Medicine" was successfully organized on four occasions, and attracted
      more than 800 participants from 55 countries [...].

PMID- 29048361
TI  - High Fat Diet with a High Monounsaturated Fatty Acid and
      Polyunsaturated/Saturated Fatty Acid Ratio Suppresses Body Fat Accumulation and
      Weight Gain in Obese Hamsters.
AB  - The aim of this study was to investigate the effect of a high fat diet with
      experimental oil consisting of 60% MUFAs (monounsaturated fatty acids) with a P/S
      ratio of 5 on fat deposition and lipid metabolism in obese hamsters. Hamsters
      were randomly assigned to a control group and a diet-induced obesity group for
      nine weeks. Then an additional eight-week experimental period began, during which
      obese hamsters were randomly divided into three groups and fed different amounts
      of the experimental oil mixture in their diets as follows: 5%, 15%, and 20% w/w
      (OB-M5, OB-M15, and OB-M20 groups, respectively). The results showed that the OB
      M15 and OB-M20 groups had significantly lower blood cholesterol and higher
      insulin levels. Compared to the control group, the three obese groups exhibited
      higher hepatic fatty acid synthase activity; however, the acyl-CoA oxidase
      activities were also enhanced. Although dietary fat content differed, there were
      no differences in energy intake, final body weights, and epididymal fat weights
      among the four groups. These results suggest that regardless of whether the
      specimens had a high fat intake or not, dietary fat containing high MUFAs with a
      high P/S ratio had beneficial effects on maintaining blood lipid profiles and may
      not result in body fat accumulation in obese hamsters, possibly by promoting
      lipolytic enzyme activities.

PMID- 29048363
TI  - Precise Placement of Metallic Nanowires on a Substrate by Localized Electric
      Fields and Inter-Nanowire Electrostatic Interaction.
AB  - Placing nanowires at the predetermined locations on a substrate represents one of
      the significant hurdles to be tackled for realization of heterogeneous nanowire
      systems. Here, we demonstrate spatially-controlled assembly of a single nanowire
      at the photolithographically recessed region at the electrode gap with high
      integration yield (~90%). Two popular routes, such as protruding electrode tips
      and recessed wells, for spatially-controlled nanowire alignment, are compared to
      investigate long-range dielectrophoretic nanowire attraction and short-range
      nanowire-nanowire electrostatic interaction for determining the final alignment
      of attracted nanowires. Furthermore, the post-assembly process has been developed
      and tested to make a robust electrical contact to the assembled nanowires, which
      removes any misaligned ones and connects the nanowires to the underlying
      electrodes of circuit.

PMID- 29048365
TI  - Integrating Autism Care through a School-Based Intervention Model: A Pilot Study.
AB  - The purpose of this pilot study is to determine the feasibility of monitoring the
      progress of children with an autism spectrum disorder (ASD) both in school and at
      home to promote a school-based integrated care model between parents, teachers,
      and medical providers. This is a prospective cohort study. To monitor progress,
      outcome measures were administered via an online platform developed for
      caregivers and teachers of children (n = 30) attending a school specializing in
      neurodevelopmental disorders and using an integrated medical and education
      program. Longitudinal analysis showed improvements in a novel scale, the Teacher
      Autism Progress Scale (TAPS), which was designed to measure key autism-related
      gains in a school environment (2.1-point improvement, p = 0.004, ES = 0.324). The
      TAPS showed a strong and statistically significant correlation, with improvement
      in aberrant behavior (r = -0.50; p = 0.008) and social responsiveness (r = -0.70;
      p < 0.001). The results also showed non-statistically significant improvements in
      aberrant behavior, social responsiveness, and quality of life over time at both
      school and home. To assess feasibility of ongoing progress measurement, we
      assessed missing data, which showed caregivers were more likely to miss surveys
      during summer. Results demonstrate the value and feasibility of online,
      longitudinal data collection in school to assist with individualized education
      planning and collaborative care for children with ASD. Lessons learned in this
      pilot will support school outcomes researchers in developing more efficacious,
      collaborative treatment plans between clinicians, caregivers, and teachers.

PMID- 29048364
TI  - Protective Effect of Argan and Olive Oils against LPS-Induced Oxidative Stress
      and Inflammation in Mice Livers.
AB  - Sepsis causes severe dysregulation of organ functions, via the development of
      oxidative stress and inflammation. These pathophysiological mechanisms are
      mimicked in mice injected with bacterial lipopolysaccharide (LPS). Here,
      protective properties of argan oil against LPS-induced oxidative stress and
      inflammation are explored in the murine model. Mice received standard chow,
      supplemented with argan oil (AO) or olive oil (OO) for 25 days, before septic
      shock was provoked with a single intraperitoneal injection of LPS, 16 hours prior
      to animal sacrifice. In addition to a rise in oxidative stress and inflammatory
      markers, injected LPS also caused hepatotoxicity, accompanied by hyperglycemia,
      hypercholesterolemia and hyperuremia. These LPS-associated toxic effects were
      blunted by AO pretreatment, as corroborated by normal plasma parameters and cell
      stress markers (glutathione: GSH) and antioxidant enzymology (catalase, CAT;
      superoxide dismutase, SOD and glutathione peroxidase, GPx). Hematoxylin-eosin
      staining revealed that AO can protect against acute liver injury, maintaining a
      normal status, which is pointed out by absent or reduced LPS-induced hepatic
      damage markers (i.e., alanine aminotransferase (ALT) and aspartate transaminase
      (AST)). Our work also indicated that AO displayed anti-inflammatory activity, due
      to down-regulations of genes encoding pro-inflammatory cytokines Interleukin-6
      (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha) and in up-regulations of the
      expression of anti-inflammatory genes encoding Interleukin-4 (IL-4) and
      Interleukin-10 (IL-10). OO provided animals with similar, though less extensive,
      protective changes. Collectively our work adds compelling evidence to the
      protective mechanisms of AO against LPS-induced liver injury and hence
      therapeutic potentialities, in regard to the management of human sepsis.
      Activations of IL-4/Peroxisome Proliferator-Activated Receptors (IL-4/PPARs)
      signaling and, under LPS, an anti-inflammatory IL-10/Liver X Receptor (IL-10/LXR)
      route, obviously indicated the high potency and plasticity of the anti
      inflammatory properties of argan oil.

PMID- 29048366
TI  - Lipase-Catalyzed Transesterification of Egg-Yolk Phophatidylcholine with
      Concentrate of n-3 Polyunsaturated Fatty Acids from Cod Liver Oil.
AB  - Phospholipids containing PUFAs are important vehicles for their delivering to the
      targeted tissues. In our research project we established enzymatic methods for
      the enrichment of natural egg-yolk PC with n-3 PUFAs. Instead of synthetic PUFA
      ethyl esters, the new strategy was developed using polyunsaturated fatty acids
      enriched fraction (PUFA-EF) from cod liver oil as the natural acyl donors. PUFA
      EF was produced by urea-complexation and contained 86.9% PUFA including 8.5%
      stearidonic acid (SDA; 18:4(n-3)), 26.7% EPA, and 45.2% DHA. The
      transesterification of PC with PUFA was catalyzed by lipases. After screening of
      enzymes the effect of reaction medium; molar ratio of substrates and etc. was
      investigated. The highest incorporation of PUFA was 45.6%; including 36.8% DHA
      and 5.8% EPA at the following reaction conditions: hexane; 55  degrees C; PUFA
      EF/PC acyl ratio of 10; 48 h of reaction time and lipase B from Candida
      antarctica as a biocatalyst (20% of enzyme load).

PMID- 29048367
TI  - Regulation of E2F1 Transcription Factor by Ubiquitin Conjugation.
AB  - Ubiquitination is a post-translational modification that defines the cellular
      fate of intracellular proteins. It can modify their stability, their activity,
      their subcellular location, and even their interacting pattern. This modification
      is a reversible event whose implementation is easy and fast. It contributes to
      the rapid adaptation of the cells to physiological intracellular variations and
      to intracellular or environmental stresses. E2F1 (E2 promoter binding factor 1)
      transcription factor is a potent cell cycle regulator. It displays contradictory
      functions able to regulate both cell proliferation and cell death. Its expression
      and activity are tightly regulated over the course of the cell cycle progression
      and in response to genotoxic stress. I discuss here the most recent evidence
      demonstrating the role of ubiquitination in E2F1's regulation.

PMID- 29048368
TI  - The Structure of Human Neuromuscular Junctions: Some Unanswered Molecular
      Questions.
AB  - The commands that control animal movement are transmitted from motor neurons to
      their target muscle cells at the neuromuscular junctions (NMJs). The NMJs contain
      many protein species whose role in transmission depends not only on their
      inherent properties, but also on how they are distributed within the complex
      structure of the motor nerve terminal and the postsynaptic muscle membrane. These
      molecules mediate evoked chemical transmitter release from the nerve and the
      action of that transmitter on the muscle. Human NMJs are among the smallest known
      and release the smallest number of transmitter "quanta". By contrast, they have
      the most deeply infolded postsynaptic membranes, which help to amplify
      transmitter action. The same structural features that distinguish human NMJs make
      them particularly susceptible to pathological processes. While much has been
      learned about the molecules which mediate transmitter release and action, little
      is known about the molecular processes that control the growth of the cellular
      and subcellular components of the NMJ so as to give rise to its mature form. A
      major challenge for molecular biologists is to understand the molecular basis for
      the development and maintenance of functionally important aspects of NMJ
      structure, and thereby to point to new directions for treatment of diseases in
      which neuromuscular transmission is impaired.

PMID- 29048369
TI  - Effect of Curcumin on the Diversity of Gut Microbiota in Ovariectomized Rats.
AB  - Curcumin has been proven to have a weight-loss effect in a menopausal rat model
      induced by ovariectomy. However, the effects of curcumin on gut microfloral
      communities of ovariectomized (OVX) rats remains unclear. Here, we used high
      throughput 16S rDNA sequencing to explore the effects of curcumin on microbial
      diversity in the gut of OVX rats. Female Wistar rats were subjected to either
      ovariectomy or a sham operation (SHAM group). The OVX rats were treated with
      vehicle (OVX group) or curcumin (CUR group) by oral gavage. After 12-week
      treatments, the weights of the bodies and uteri of rats were recorded, the levels
      of estradiol in the serum were assayed by electrochemiluminescence immunoassay
      (ECLIA). Then, the fragments encompassing V3-V4 16S rDNA hypervariable regions
      were PCR amplified from fecal samples, and the PCR products of V3-V4 were
      sequenced on an Illumina MiSeq for characterization of the gut microbiota. Our
      results showed that, compared to rats in the SHAM group, rats in the OVX group
      had more weight gain and lower levels of estradiol in the serum, and curcumin
      could cause significant weight loss in OVX rats but did not increase the levels
      of estradiol. Sequencing results revealed the presence of 1120, 1114, and 1119
      operational taxonomic units (OTUs) found in the SHAM, OVX, and CUR groups,
      respectively. The percentage of shared OTUs was 86.1603%. Gut microbiota of rats
      from the SHAM or CUR group had higher levels of biodiversity and unevenness
      estimations than those from the OVX group. At the phyla level, compared to rats
      in SHAM group, rats in the OVX group had a higher ratio of phyla Firmicutes and
      Bacteroidetes in the gut; at the genus level, four differential gut microbiota
      (Incertae_Sedis, Anaerovorax, Anaerotruncus, and Helicobacter) between SHAM and
      OVX groups were found, whereas seven differential gut microbiota (Serratia,
      Anaerotruncus, Shewanella, Pseudomonas, Papillibacter, Exiguobacterium, and
      Helicobacter) between OVX and CUR groups were found. In conclusion, estrogen
      deficiency induced by ovariectomy caused changes in the distribution and
      structure of intestinal microflora in rats, and curcumin could partially reverse
      changes in the diversity of gut microbiota.

PMID- 29048371
TI  - ZnT3 Gene Deletion Reduces Colchicine-Induced Dentate Granule Cell Degeneration.
AB  - Our previous study demonstrated that colchicine-induced dentate granule cell
      death is caused by blocking axonal flow and the accumulation of intracellular
      zinc. Zinc is concentrated in the synaptic vesicles via zinc transporter 3
      (ZnT3), which facilitates zinc transport from the cytosol into the synaptic
      vesicles. The aim of the present study was to identify the role of ZnT3 gene
      deletion on colchicine-induced dentate granule cell death. The present study used
      young (3-5 months) mice of the wild-type (WT) or the ZnT3-/- genotype. Colchicine
      (10 ug/kg) was injected into the hippocampus, and then brain sections were
      evaluated 12 or 24 h later. Cell death was evaluated by Fluoro-Jade B; oxidative
      stress was analyzed by 4-hydroxy-2-nonenal; and dendritic damage was detected by
      microtubule-associated protein 2. Zinc accumulation was detected by N-(6-methoxy
      8-quinolyl)-para-toluenesulfonamide (TSQ) staining. Here, we found that ZnT3-/-
      reduced the number of degenerating cells after colchicine injection. The ZnT3-/-
      mediated inhibition of cell death was accompanied by suppression of oxidative
      injury, dendritic damage and zinc accumulation. In addition, ZnT3-/- mice showed
      more glutathione content than WT mice and inhibited neuronal glutathione
      depletion by colchicine. These findings suggest that increased neuronal
      glutathione by ZnT3 gene deletion prevents colchicine-induced dentate granule
      cell death.

PMID- 29048372
TI  - alpha-Synuclein Regulates Neuronal Cholesterol Efflux.
AB  - alpha-Synuclein is a neuronal protein that is at the center of focus in
      understanding the etiology of a group of neurodegenerative diseases called alpha
      synucleinopathies, which includes Parkinson's disease (PD). Despite much
      research, the exact physiological function of alpha-synuclein is still unclear.
      alpha-Synuclein has similar biophysical properties as apolipoproteins and other
      lipid-binding proteins and has a high affinity for cholesterol. These properties
      suggest a possible role for alpha-synuclein as a lipid acceptor mediating
      cholesterol efflux (the process of removing cholesterol out of cells). To test
      this concept, we "loaded" SK-N-SH neuronal cells with fluorescently-labelled
      cholesterol, applied exogenous alpha-synuclein, and measured the amount of
      cholesterol removed from the cells using a classic cholesterol efflux assay. We
      found that alpha-synuclein potently stimulated cholesterol efflux. We found that
      the process was dose and time dependent, and was saturable at 1.0 ug/mL of alpha
      synuclein. It was also dependent on the transporter protein ABCA1 located on the
      plasma membrane. We reveal for the first time a novel role of alpha-synuclein
      that underscores its importance in neuronal cholesterol regulation, and identify
      novel therapeutic targets for controlling cellular cholesterol levels.

PMID- 29048370
TI  - Migration Rate Inhibition of Breast Cancer Cells Treated by Caffeic Acid and
      Caffeic Acid Phenethyl Ester: An In Vitro Comparison Study.
AB  - One of the deadliest cancers among women is a breast cancer. Research has shown
      that two natural substances occurring in propolis, caffeic acid (CA) and caffeic
      acid phenethyl ester (CAPE), have significant anticancer effects. The purpose of
      our in vitro study was to compare cytotoxic activity and migration rate
      inhibition using CA and CAPE (doses of 50 and 100 um) against triple-negative,
      MDA-MB-231 breast adenocarcinoma line cells, drawn from Caucasian women.
      Viability was measured by XTT-NR-SRB assay (Tetrazolium hydroxide-Neutral Red
      Sulforhodamine B) for 24 h and 48 h periods. Cell migration for wound healing
      assay was taken for 0 h, 8 h, 16 h, and 24 h periods. CAPE displayed more than
      two times higher cytotoxicity against MDA-MB-231 cells. IC50 values for the XTT
      assay were as follows: CA for 24 h and 48 h were 150.94 uM and 108.42 uM,
      respectively, while CAPE was 68.82 uM for 24 h and 55.79 uM for 48 h. For the NR
      assay: CA was 135.85 uM at 24 h and 103.23 uM at 48 h, while CAPE was 64.04 uM at
      24 h and 53.25 uM at 48 h. For the SRB assay: CA at 24 h was 139.80 uM and at 48
      h 103.98 uM, while CAPE was 66.86 uM at 24 h and 47.73 uM at 48 h. Both agents
      suspended the migration rate; however, CAPE displayed better activity. Notably,
      for the 100 uM CAPE dose, motility of the tested breast carcinoma cells was
      halted.

PMID- 29048373
TI  - Individual and Environmental Correlates to Quality of Life in Park Users in
      Colombia.
AB  - Purpose: To explore individual and environmental correlates to quality of life
      (QoL) in park users in Colombia. Methods: A cross-sectional study with face-to
      face interviews was conducted with 1392 park users from ten parks in Colombia.
      The survey included sociodemographic questions, health condition assessed with
      EuroQuol-5-Dimensions-5-Levels; in addition, questions about accessibility to the
      parks and perceptions about quality of infrastructure and green areas were asked.
      The Spanish version of the questionnaire EUROHIS-QOL-8 items was applied to
      assess QoL. Log-binomial regression models were applied for analyses. Results:
      Years of schooling, visits to the park with a companion, active use of the park,
      a maximum score for quality of trees and walking paths, and the perception of
      safety on the way to the park were positively associated with a better QoL (p <
      0.05). Health conditions related to problems in the ability to perform activities
      of daily living and anxiety/depression showed negative associations. Conclusions:
      The present study contributes to the Latin American studies by providing
      information on how parks in an intermediate city may contribute to increased QoL
      of park users through safety in neighborhoods, social support, active use, and
      aesthetics, cleanliness, and care of green areas.

PMID- 29048374
TI  - Brain and Hepatic Mt mRNA Is Reduced in Response to Mild Energy Restriction and n
      3 Polyunsaturated Fatty Acid Deficiency in Juvenile Rats.
AB  - Metallothioneins (MTs) perform important regulatory and cytoprotective functions
      in tissues including the brain. While it is known that energy restriction (ER)
      and dietary n-3 polyunsaturated fatty acid (PUFA) deficiency impact postnatal
      brain growth and development, little data exist regarding the impact of
      undernutrition upon MT expression in growing animals. We tested the hypothesis
      that ER with and without dietary n-3 PUFA deficiency reduces MT expression in
      juvenile rats. ER rats were individually pair-fed at 75% of the ad libitum (AL)
      intake of control rats provided diets consisting of either soybean oil (SO) that
      is alpha-linolenic acid (ALA; 18:3n-3) sufficient or corn oil (CO; ALA
      deficient). Fatty acids (FA) and metal concentrations of liver and brain regions
      were analyzed. Tissue expression of MTs (Mt1-3) and modulators of MT expression
      including glucocorticoid receptors (Nr3c1 and Nr3c2) and several mediators of
      thyroid hormone regulation (Dio1-3, Mct8, Oatp1c1, Thra, and Thrb) were measured.
      Plasma corticosterone and triiodothyronine levels were also evaluated. ER, but
      not metal deficiency, reduced Mt2 expression in the cerebellum (50%) and cerebral
      cortex (23%). In liver, a reduction in dietary n-3 PUFA reduced Mt1, Mt2, Nr3c1,
      Mct8, and Thrb. ER elevated Nr3c1, Dio1, and Thrb and reduced Thra in the liver.
      Given MT's role in cellular protection, further studies are needed to evaluate
      whether ER or n-3 PUFA deficiency may leave the juvenile brain and/or liver more
      susceptible to endogenous or environmental stressors.

PMID- 29048375
TI  - Construction of a Bivalent Thrombin Binding Aptamer and Its Antidote with
      Improved Properties.
AB  - Aptamers are short synthetic DNA or RNA oligonucleotides that adopt secondary and
      tertiary conformations based on Watson-Crick base-pairing interactions and can be
      used to target a range of different molecules. Two aptamers, HD1 and HD22, that
      bind to exosites I and II of the human thrombin molecule, respectively, have been
      extensively studied due to their anticoagulant potentials. However, a fundamental
      issue preventing the clinical translation of many aptamers is degradation by
      nucleases and reduced pharmacokinetic properties requiring higher dosing regimens
      more often. In this study, we have chemically modified the design of previously
      described thrombin binding aptamers targeting exosites I, HD1, and exosite II,
      HD22. The individual aptamers were first modified with an inverted deoxythymidine
      nucleotide, and then constructed bivalent aptamers by connecting the HD1 and HD22
      aptamers either through a triethylene glycol (TEG) linkage or four consecutive
      deoxythymidines together with an inverted deoxythymidine nucleotide at the 3'
      end. The anticoagulation potential, the reversal of coagulation with different
      antidote sequences, and the nuclease stability of the aptamers were then
      investigated. The results showed that a bivalent aptamer RNV220 containing an
      inverted deoxythymidine and a TEG linkage chemistry significantly enhanced the
      anticoagulation properties in blood plasma and nuclease stability compared to the
      existing aptamer designs. Furthermore, a bivalent antidote sequence RNV220AD
      efficiently reversed the anticoagulation effect of RNV220 in blood plasma. Based
      on our results, we believe that RNV220 could be developed as a potential
      anticoagulant therapeutic molecule.

PMID- 29048376
TI  - New Methods of Esterification of Nanodiamonds in Fighting Breast Cancer-A Density
      Functional Theory Approach.
AB  - The use of nanodiamonds as anticancer drug delivery vehicles has received much
      attention in recent years. In this theoretical paper, we propose using different
      esterification methods for nanodiamonds. The monomers proposed are 2
      hydroxypropanal, polyethylene glycol, and polyglicolic acid. Specifically, the
      hydrogen bonds, infrared (IR) spectra, molecular polar surface area, and
      reactivity parameters are analyzed. The monomers proposed for use in
      esterification follow Lipinski's rule of five, meaning permeability is good, they
      have good permeation, and their bioactivity is high. The results show that the
      complex formed between tamoxifen and nanodiamond esterified with polyglicolic
      acid presents the greatest number of hydrogen bonds and a good amount of
      molecular polar surface area. Calculations concerning the esterified nanodiamond
      and reactivity parameters were performed using Density Functional Theory with the
      M06 functional and the basis set 6-31G (d); for the esterified nanodiamond
      Tamoxifen complexes, the semi-empirical method PM6 was used. The solvent effect
      has been taken into account by using implicit modelling and the conductor-like
      polarizable continuum model.

PMID- 29048377
TI  - Nucleation/Growth Mechanisms and Morphological Evolution of Porous MnO2 Coating
      Deposited on Graphite for Supercapacitor.
AB  - The nucleation and growth mechanisms of porous MnO2 coating deposited on graphite
      in MnSO4 solution were investigated in detail by cyclic voltammetry,
      chronoamperometry and scanning electron microscopy. The electrochemical
      properties of honeycomb-like MnO2 were evaluated by cycle voltammetry and
      galvanostatic charge-discharge. Results indicated that MnO2 was synthesized by
      the following steps: Mn2+-> Mn3++ e-, Mn3++2H2O -> MnOOH + 3H+, and MnOOH -> MnO2
      + H++ e-. The deposition of MnO2 was divided into four stages. A short incubation
      period (approximately 1.5 s) was observed, prior to nucleation. The decreasing
      trend of the current slowed as time increased due to nucleation and MnO2 growth
      in the second stage. A huge number of nuclei were formed by instantaneous
      nucleation, and these nuclei grew and connected with one another at an
      exceedingly short time (0.5 s). In the third stage, the gaps in-between initial
      graphite flakes were filled with MnO2 until the morphology of the flakes
      gradually became similar to that of the MnO2-deposited layer. In the fourth
      stage, the graphite electrode was covered completely with a thick and dense layer
      of MnO2 deposits. All MnO2 electrodes at different deposition times obtained
      nearly the same specific capacitance of approximately 186 F/g, thus indicating
      that the specific capacitance of the electrodes is not related with deposition
      time.

PMID- 29048379
TI  - Impacts of Modification of Alloying Method on Inclusion Evolution in RH Refining
      of Silicon Steel.
AB  - This study explores the effect of introducing additional alloy elements not only
      in a different order but also at different stages of the Ruhrstahl-Heraeus (RH)
      process of low-carbon silicon steel production. A more economical method,
      described as "pre-alloying", has been introduced. The evolution of MnO-FeO
      inclusions produced by pre-alloying was investigated. Results show that spherical
      3FeO.MnO inclusions form first, then shelled FeO.zMnO (z = 0.7-4) inclusions
      nucleate on the surface of pre-existing 3FeO.MnO. Spherical FeO.zMnO (z = 3-5) is
      further evolved from shelled 3FeO.MnO by diffusion. Because these MnO-FeO
      inclusions float up into the slag before degassing, the pre-alloying process does
      not affect the quality of the melt in the end. Both carbon content and inclusion
      size conform to industry standards.

PMID- 29048378
TI  - Analysis of Non-Volatile Chemical Constituents of Menthae Haplocalycis Herba by
      Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry.
AB  - Menthae Haplocalycis herba, one kind of Chinese edible herbs, has been widely
      utilized for the clinical use in China for thousands of years. Over the last
      decades, studies on chemical constituents of Menthae Haplocalycis herba have been
      widely performed. However, less attention has been paid to non-volatile
      components which are also responsible for its medical efficacy than the volatile
      constituents. Therefore, a rapid and sensitive method was developed for the
      comprehensive identification of the non-volatile constituents in Menthae
      Haplocalycis herba using ultra-high performance liquid chromatography coupled
      with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap). Separation
      was performed with Acquity UPLC(r) BEH C18 column (2.1 mm * 100 mm, 1.7 MUm) with
      0.2% formic acid aqueous solution and acetonitrile as the mobile phase under
      gradient conditions. Based on the accurate mass measurement (<5 ppm), MS/MS
      fragmentation patterns and different chromatographic behaviors, a total of 64
      compounds were unambiguously or tentatively characterized, including 30
      flavonoids, 20 phenolic acids, 12 terpenoids and two phenylpropanoids. Finally,
      target isolation of three compounds named Acacetin, Rosmarinic acid and
      Clemastanin A (first isolated from Menthae Haplocalycis herba) were performed
      based on the obtained results, which further confirmed the deduction of
      fragmentation patterns and identified the compounds profile in Menthae
      Haplocalycis herba. Our research firstly systematically elucidated the non
      volatile components of Menthae Haplocalycis herba, which laid the foundation for
      further pharmacological and metabolic studies. Meanwhile, our established method
      was useful and efficient to screen and identify targeted constituents from
      traditional Chinese medicine extracts.

PMID- 29048380
TI  - Hop Phytochemicals and Their Potential Role in Metabolic Syndrome Prevention and
      Therapy.
AB  - Historically, hop cones (Humulus lupulus) have been used since ancient times as a
      remedy for many ailments and, as a source of polyphenols and bitter acids, is
      very effective in the treatment of metabolic syndrome (MS). Hop flavonoids,
      particularly xanthohumol (XN), are substances with hypoglycemic,
      antihyperlipidemic, and antiobesity activities. Iso-alpha-acids (IAA) and matured
      hop bitter acids (MHBA) improve health by influencing lipid metabolism, glucose
      tolerance, and body weight. The modulatory effect of IAA and MHBA on lipid
      metabolism may also be responsible for a loss in body weight. These results
      suggest promising applications for IAA, MHBA, and XN in humans, particularly in
      the prevention of diet-induced obesity and diabetes.

PMID- 29048381
TI  - Self-Assembly with 2,6-Bis(1-(pyridin-4-ylmethyl)-1H-1,2,3-triazol-4-yl)pyridine:
      Silver(I) and Iron(II) Complexes.
AB  - A new "click" ligand, 2,6-bis(1-(pyridin-4-ylmethyl)-1H-1,2,3-triazol-4
      yl)pyridine (L) featuring a tridentate 2,6-bis(1,2,3-triazol-4-yl)pyridine
      (tripy) pocket and two pyridyl (py) units was synthesized in modest yield (42%)
      using the copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The
      coordination chemistry of the ligand with silver(I) and iron(II) ions was
      examined using a battery of solution (1H and DOSY (diffusion ordered
      spectroscopy) nuclear magnetic resonance (NMR), infrared and absorption
      spectroscopies, high-resolution electrospray ionization mass spectrometry (HR-ESI
      MS)), and solid state (X-ray crystallography, elemental analysis) techniques.
      When treated with silver(I) ions, the ligand forms discrete [Ag(L)]+ (X-, where X
      = BF4-, NO3- or SbF6-) complexes in dimethyl sulfoxide (DMSO) solution but these
      complexes crystallize as coordination polymers. The addition of [Fe(H2O)6](BF4)2
      to an acetonitrile solution of the ligand forms the expected monomeric octahedral
      [Fe(L)2]2+ complex and treatment of the iron(II) complex with AgBF4 generates a
      heterometallic linear coordination polymer.

PMID- 29048382
TI  - Living Arrangements and Health-Related Quality of Life in Chinese Adolescents Who
      Migrate from Rural to Urban Schools: Mediating Effect of Social Support.
AB  - Changes in living arrangements (from living with, or not living with family) may
      affect the health-related quality of life (HRQoL). This study aimed to
      investigate the impact of living arrangement on HRQoL among adolescents migrating
      from rural to urban schools, and whether social support, in addition to living
      with a family, had an impact. A cross-sectional survey of 459 school adolescents
      was carried out in two public schools in Guyuan County, Ningxia Hui Autonomous
      Region, China in 2015. The survey contained the following questionnaires: a self
      designed questionnaire, the 12-item Short Form Health Survey (SF-12), and the
      Social Support Rating Scale (SSRS). Of the 459 adolescents sampled (aged 15.41 +/
      1.07 years with range of 13 to 18), 61.7% were living with family, and 38.3%
      were not living with family. Those students not living with families had lower
      Mental Component Scale (MCS) scores as well as less social support overall. Those
      students, who were not living with families, also reported more chronic health
      problems and more alcohol consumption compared to those students living with
      families. Social support was a statistically significant mediating factor on the
      effect of living arrangements on MCS. Our findings demonstrated that those
      students, who were not living with families, tended to have more health-related
      quality of life issues, but social support partially mediated the relationship
      between living arrangements and health.

PMID- 29048383
TI  - Is There a Causal Relationship between Intussusception and Food Allergy?
AB  - Although intussusception and food allergy are common health problems in
      childhood, the relation between these two diseases remain obscure. The aim of
      this study is to investigate the relationship between food allergy and
      intussusception, and the factors associated with both. Patients diagnosed with
      intussusception by the Brighton Collaboration Intussusception Working Group
      criteria were prospectively investigated for food allergy per the European
      Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)
      Guideline. They were analyzed per demographic features, clinical, physical and
      laboratory findings. There were eight (38.1%) patients diagnosed with food
      allergy, while 13 (61.9%) patients were non-allergic. The mean number of days of
      presenting symptoms was 1.13 days in the allergy group and 7.85 days in the non
      allergy group. The mean number of intussusception attacks was 1.63 in the allergy
      group while 1 in the non-allergy group (p < 0.05, relative risk (RR) = 2.6). In
      the allergy group, one (13%) patient was followed up, six (75%) patients were
      reduced with pneumatic and one (13%) patient reduced manually. In the non-allergy
      group, four (31%) patients were followed up, six (46%) patients were reduced with
      pneumotic, one (7%) patient was reduced manually, and resection anastomosis was
      performed in two (15%) patients. Food allergy is an unrecognized associated
      factor for intussusception patients, which increases the risk for recurrence. Due
      to the small patient population, these results should be interpreted with
      caution.

PMID- 29048386
TI  - Leveraging the Domain of Work to Improve Migrant Health.
AB  - Work is a principal driver of current international migration, a primary social
      determinant of health, and a fundamental point of articulation between migrants
      and their host society. Efforts by international organizations to promote migrant
      health have traditionally focused on infectious diseases and access to
      healthcare, while international labor organizations have largely focused on
      issues of occupational health. The underutilization of the domain of work in
      addressing the health of migrants is truly a missed opportunity for influencing
      worker well-being and reducing societal economic burden. Understanding of the
      relationships among migration, work, and health would facilitate further
      integration of migrant health concerns into the policy agenda of governments and
      international agencies that work at the nexus of labor, health and development.
      The domain of work offers an opportunity to capitalize on the existing health and
      development infrastructure and leverage technical resources, programs and
      research to promote migrant health. It also provides the opportunity to advance
      migrant health through new and innovative approaches and partnerships.

PMID- 29048385
TI  - Disease and Health Inequalities Attributable to Air Pollutant Exposure in
      Detroit, Michigan.
AB  - The environmental burden of disease is the mortality and morbidity attributable
      to exposures of air pollution and other stressors. The inequality metrics used in
      cumulative impact and environmental justice studies can be incorporated into
      environmental burden studies to better understand the health disparities of
      ambient air pollutant exposures. This study examines the diseases and health
      disparities attributable to air pollutants for the Detroit urban area. We
      apportion this burden to various groups of emission sources and pollutants, and
      show how the burden is distributed among demographic and socioeconomic subgroups.
      The analysis uses spatially-resolved estimates of exposures, baseline health
      rates, age-stratified populations, and demographic characteristics that serve as
      proxies for increased vulnerability, e.g., race/ethnicity and income. Based on
      current levels, exposures to fine particulate matter (PM2.5), ozone (O3), sulfur
      dioxide (SO2), and nitrogen dioxide (NO2) are responsible for more than 10,000
      disability-adjusted life years (DALYs) per year, causing an annual monetized
      health impact of $6.5 billion. This burden is mainly driven by PM2.5 and O3
      exposures, which cause 660 premature deaths each year among the 945,000
      individuals in the study area. NO2 exposures, largely from traffic, are important
      for respiratory outcomes among older adults and children with asthma, e.g., 46%
      of air-pollution related asthma hospitalizations are due to NO2 exposures. Based
      on quantitative inequality metrics, the greatest inequality of health burdens
      results from industrial and traffic emissions. These metrics also show
      disproportionate burdens among Hispanic/Latino populations due to industrial
      emissions, and among low income populations due to traffic emissions.
      Attributable health burdens are a function of exposures, susceptibility and
      vulnerability (e.g., baseline incidence rates), and population density. Because
      of these dependencies, inequality metrics should be calculated using the
      attributable health burden when feasible to avoid potentially underestimating
      inequality. Quantitative health impact and inequality analyses can inform health
      and environmental justice evaluations, providing important information to
      decision makers for prioritizing strategies to address exposures at the local
      level.

PMID- 29048387
TI  - Vitamin D as a Novel Regulator of Tumor Metabolism: Insights on Potential
      Mechanisms and Implications for Anti-Cancer Therapy.
AB  - 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the bioactive form of vitamin D, has been
      shown to possess significant anti-tumor potential. While most studies so far have
      focused on the ability of this molecule to influence the proliferation and
      apoptosis of cancer cells, more recent data indicate that 1,25(OH)2D3 also
      impacts energy utilization in tumor cells. In this article, we summarize and
      review the evidence that demonstrates the targeting of metabolic aberrations in
      cancers by 1,25(OH)2D3, and highlight potential mechanisms through which these
      effects may be executed. We shed light on the ability of this molecule to
      regulate metabolism-related tumor suppressors and oncogenes, energy- and nutrient
      sensing pathways, as well as cell death and survival mechanisms such as
      autophagy.

PMID- 29048384
TI  - The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and
      HIV-1 Pathogenesis.
AB  - The T helper 17 (Th17) cells represent a subset of CD4+ T-cells with unique
      effector functions, developmental plasticity, and stem-cell features. Th17 cells
      bridge innate and adaptive immunity against fungal and bacterial infections at
      skin and mucosal barrier surfaces. Although Th17 cells have been extensively
      studied in the context of autoimmunity, their role in various other pathologies
      is underexplored and remains an area of open investigation. This review
      summarizes the history of Th17 cell discovery and the current knowledge relative
      to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis.
      We further discuss the concept of Th17 pathogenicity in the context of
      autoimmunity, cancer, and HIV infection, and we review the most recent
      discoveries on molecular mechanisms regulating HIV replication/persistence in
      pathogenic Th17 cells. Finally, we stress the need for novel fundamental research
      discovery-based Th17-specific therapeutic interventions to treat pathogenic
      conditions associated with Th17 abnormalities, including HIV infection.

PMID- 29048388
TI  - Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment
      in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette
      Guerin: A Long-Term Follow-Up Study of a Japanese Cohort.
AB  - The clinical significance of regulatory T cells (Treg) and tumor-associated
      macrophages (TAM) in the tumor microenvironment of human bladder cancer remains
      unclear. The aim of this study is to explore their relevance to oncological
      features in non-muscle invasive bladder cancer (NMIBC). We carried out
      immunohistochemical analysis of forkhead box P3 (FOXP3, Treg maker), CD204 (TAM
      marker), and interleukin-6 (IL6) using surgical specimens obtained from 154 NMIBC
      patients. The Treg and TAM counts surrounding the cancer lesion and IL6-positive
      cancer cell counts were evaluated against clinicopathological variables. We
      focused on the ability of the Treg and TAM counts around the cancer lesion to
      predict outcomes after adjuvant intravesical Bacille Calmette-Guerin (BCG)
      treatment. High Treg counts were associated with female patients, older age, T1
      category, and high tumor grade. TAM count was significantly correlated with Treg
      count and with IL6-positive cancer cell count. In our analysis of 71 patients
      treated with BCG, high counts of Treg and TAM were associated with shorter
      recurrence-free survival, and the former was an independent predictor of
      recurrence. Poor response to intravesical BCG was associated with Treg and TAM in
      the tumor microenvironment. Disrupting the immune network can be a supplementary
      therapeutic approach for NMIBC patients receiving intravesical BCG.

PMID- 29048389
TI  - Discovery of Novel N-Substituted Prolinamido Indazoles as Potent Rho Kinase
      Inhibitors and Vasorelaxation Agents.
AB  - Inhibitors of Rho kinase (ROCK) have potential therapeutic applicability in a
      wide range of diseases, such as hypertension, stroke, asthma and glaucoma. In a
      previous article, we described the lead discovery of DL0805, a new ROCK I
      inhibitor, showing potent inhibitory activity (IC50 6.7 MUM). Herein, we present
      the lead optimization of compound DL0805, resulting in the discovery of 24- and
      39-fold more-active analogues 4a (IC50 0.27 MUM) and 4b (IC50 0.17 MUM), among
      other active analogues. Moreover, ex-vivo studies demonstrated that 4a and 4b
      exhibited comparable vasorelaxant activity to the approved drug fasudil in rat
      aortic rings. The research of a preliminary structure-activity relationship (SAR)
      indicated that the target compounds containing a beta-proline moiety have
      improved activity against ROCK I relative to analogues bearing an alpha-proline
      moiety, and among the series of the derivatives with a beta-proline-derived
      indazole scaffold, the inhibitory activity of the target compounds with a benzyl
      substituent is superior to those with a benzoyl substituent.

PMID- 29048390
TI  - Enhanced UV-Visible Light Photocatalytic Activity by Constructing Appropriate
      Heterostructures between Mesopore TiO2 Nanospheres and Sn3O4 Nanoparticles.
AB  - Novel TiO2/Sn3O4 heterostructure photocatalysts were ingeniously synthesized via
      a scalable two-step method. The impressive photocatalytic abilities of the
      TiO2/Sn3O4 sphere nanocomposites were validated by the degradation test of methyl
      orange and *OH trapping photoluminescence experiments under ultraviolet (UV) and
      visible light irradiation, respectively. Especially under the visible light, the
      TiO2/Sn3O4 nanocomposites demonstrated a superb photocatalytic activity, with
      81.2% of methyl orange (MO) decomposed at 30 min after irradiation, which greatly
      exceeded that of the P25 (13.4%), TiO2 (0.5%) and pure Sn3O4 (59.1%)
      nanostructures. This enhanced photocatalytic performance could be attributed to
      the mesopore induced by the monodispersed TiO2 cores that supply sufficient
      surface areas and accessibility to reactant molecules. This exquisite hetero
      architecture facilitates extended UV-visible absorption and efficient
      photoexcited charge carrier separation.

PMID- 29048392
TI  - Terahertz Spectroscopy for Proximal Soil Sensing: An Approach to Particle Size
      Analysis.
AB  - Spatially resolved soil parameters are some of the most important pieces of
      information for precision agriculture. These parameters, especially the particle
      size distribution (texture), are costly to measure by conventional laboratory
      methods, and thus, in situ assessment has become the focus of a new discipline
      called proximal soil sensing. Terahertz (THz) radiation is a promising method for
      nondestructive in situ measurements. The THz frequency range from 258 gigahertz
      (GHz) to 350 GHz provides a good compromise between soil penetration and the
      interaction of the electromagnetic waves with soil compounds. In particular, soil
      physical parameters influence THz measurements. This paper presents
      investigations of the spectral transmission signals from samples of different
      particle size fractions relevant for soil characterization. The sample thickness
      ranged from 5 to 17 mm. The transmission of THz waves was affected by the main
      mineral particle fractions, sand, silt and clay. The resulting signal changes
      systematically according to particle sizes larger than half the wavelength. It
      can be concluded that THz spectroscopic measurements provide information about
      soil texture and penetrate samples with thicknesses in the cm range.

PMID- 29048391
TI  - Downhole Applications of Magnetic Sensors.
AB  - In this paper we present a review of the application of two types of magnetic
      sensors-fluxgate magnetometers and nuclear magnetic resonance (NMR) sensors-in
      the oil/gas industry. These magnetic sensors play a critical role in drilling
      wells safely, accurately and efficiently into a target reservoir zone by
      providing directional data of the well and acquiring information about the
      surrounding geological formations. Research into magnetic sensors for oil/gas
      drilling has not been explored by researchers to the same extent as other
      applications, such as biomedical, magnetic storage and automotive/aerospace
      applications. Therefore, this paper aims to serve as an opportunity for
      researchers to truly understand how magnetic sensors can be used in a downhole
      environment and to provide fertile ground for research and development in this
      area. A look ahead, discussing other magnetic sensor technologies that can
      potentially be used in the oil/gas industry is presented, and what is still
      needed in order deploy them in the field is also addressed.

PMID- 29048393
TI  - A Research on Low Modulus Distributed Fiber Optical Sensor for Pavement Material
      Strain Monitoring.
AB  - The accumulated irreversible deformation in pavement under repeated vehicle
      loadings will cause fatigue failure of asphalt concrete. It is necessary to
      monitor the mechanical response of pavement under load by using sensors. Previous
      studies have limitations in modulus accommodation between the sensor and asphalt
      pavement, and it is difficult to achieve the distributed monitoring goal. To
      solve these problems, a new type of low modulus distributed optical fiber sensor
      (DOFS) for asphalt pavement strain monitoring is fabricated. Laboratory
      experiments have proved the applicability and accuracy of the newly-designed
      sensor. This paper presents the results of the development.

PMID- 29048394
TI  - Photoplethysmography Signal Analysis for Optimal Region-of-Interest Determination
      in Video Imaging on a Built-In Smartphone under Different Conditions.
AB  - Smartphones and tablets are widely used in medical fields, which can improve
      healthcare and reduce healthcare costs. Many medical applications for smartphones
      and tablets have already been developed and widely used by both health
      professionals and patients. Specifically, video recordings of fingertips made
      using a smartphone camera contain a pulsatile component caused by the cardiac
      pulse equivalent to that present in a photoplethysmographic signal. By performing
      peak detection on the pulsatile signal, it is possible to estimate a continuous
      heart rate and a respiratory rate. To estimate the heart rate and respiratory
      rate accurately, which pixel regions of the color bands give the most optimal
      signal quality should be investigated. In this paper, we investigate signal
      quality to determine the best signal quality by the largest amplitude values for
      three different smartphones under different conditions. We conducted several
      experiments to obtain reliable PPG signals and compared the PPG signal strength
      in the three color bands when the flashlight was both on and off. We also
      evaluated the intensity changes of PPG signals obtained from the smartphones with
      motion artifacts and fingertip pressure force. Furthermore, we have compared the
      PSNR of PPG signals of the full-size images with that of the region of interests
      (ROIs).

PMID- 29048395
TI  - Environmental Risk Assessment Strategy for Nanomaterials.
AB  - An Environmental Risk Assessment (ERA) for nanomaterials (NMs) is outlined in
      this paper. Contrary to other recent papers on the subject, the main data
      requirements, models and advancement within each of the four risk assessment
      domains are described, i.e., in the: (i) materials, (ii) release, fate and
      exposure, (iii) hazard and (iv) risk characterisation domains. The material,
      which is obviously the foundation for any risk assessment, should be described
      according to the legislatively required characterisation data. Characterisation
      data will also be used at various levels within the ERA, e.g., exposure
      modelling. The release, fate and exposure data and models cover the input for
      environmental distribution models in order to identify the potential (PES) and
      relevant exposure scenarios (RES) and, subsequently, the possible release routes,
      both with regard to which compartment(s) NMs are distributed in line with the
      factors determining the fate within environmental compartment. The initial
      outcome in the risk characterisation will be a generic Predicted Environmental
      Concentration (PEC), but a refined PEC can be obtained by applying specific
      exposure models for relevant media. The hazard information covers a variety of
      representative, relevant and reliable organisms and/or functions, relevant for
      the RES and enabling a hazard characterisation. The initial outcome will be
      hazard characterisation in test systems allowing estimating a Predicted No-Effect
      concentration (PNEC), either based on uncertainty factors or on a NM adapted
      version of the Species Sensitivity Distributions approach. The risk
      characterisation will either be based on a deterministic risk ratio approach
      (i.e., PEC/PNEC) or an overlay of probability distributions, i.e., exposure and
      hazard distributions, using the nano relevant models.

PMID- 29048396
TI  - Time Multiplexed Active Neural Probe with 1356 Parallel Recording Sites.
AB  - We present a high electrode density and high channel count CMOS (complementary
      metal-oxide-semiconductor) active neural probe containing 1344 neuron sized
      recording pixels (20 um * 20 um) and 12 reference pixels (20 um * 80 um), densely
      packed on a 50 um thick, 100 um wide, and 8 mm long shank. The active electrodes
      or pixels consist of dedicated in-situ circuits for signal source amplification,
      which are directly located under each electrode. The probe supports the
      simultaneous recording of all 1356 electrodes with sufficient signal to noise
      ratio for typical neuroscience applications. For enhanced performance, further
      noise reduction can be achieved while using half of the electrodes (678). Both of
      these numbers considerably surpass the state-of-the art active neural probes in
      both electrode count and number of recording channels. The measured input
      referred noise in the action potential band is 12.4 uVrms, while using 678
      electrodes, with just 3 uW power dissipation per pixel and 45 uW per read-out
      channel (including data transmission).

PMID- 29048397
TI  - Correlation Analysis of PM10 and the Incidence of Lung Cancer in Nanchang, China.
AB  - Air pollution and lung cancer are closely related. In 2013, the World Health
      Organization listed outdoor air pollution as carcinogenic and regarded it as the
      most widespread carcinogen that humans are currently exposed to. Here, grey
      correlation and data envelopment analysis methods are used to determine the
      pollution factors causing lung cancer among residents in Nanchang, China, and
      identify population segments which are more susceptible to air pollution. This
      study shows that particulate matter with particle sizes below 10 micron (PM10) is
      most closely related to the incidence of lung cancer among air pollution factors
      including annual mean concentrations of SO2, NO2, PM10, annual haze days, and
      annual mean Air Pollution Index/Air Quality Index (API/AQI). Air pollution has a
      greater impact on urban inhabitants as compared to rural inhabitants. When gender
      differences are considered, women are more likely to develop lung cancer due to
      air pollution. Smokers are more likely to suffer from lung cancer. These results
      provide a reference for the government to formulate policies to reduce air
      pollutant emissions and strengthen anti-smoking measures.

PMID- 29048398
TI  - Glucopyranosylidene-Spiro-Thiazolinones: Synthetic Studies and Determination of
      Absolute Configuration by TDDFT-ECD Calculations.
AB  - Reactions of O-peracylated C-(1-bromo-beta-d-glucopyranosyl)formamides with
      thioamides furnished the corresponding glucopyranosylidene-spiro-thiazolin-4-one.
      While O-debenzoylations under a variety of conditions resulted in decomposition,
      during O-deacetylations the addition of MeOH to the thiazolinone moiety was
      observed, and with EtOH and water similar adducts were isolated or detected. The
      structure and stereochemistry of the new compounds were established by means of
      NMR and electronic circular dichroism (ECD) data supported by time-dependent
      density functional theory ECD (TDDFT-ECD) calculations. TDDFT-ECD calculations
      could efficiently distinguish the proposed epimeric products having different
      absolute configuration in the spiro heterocyclic ring.

PMID- 29048399
TI  - Rapid Screening of Active Components with an Osteoclastic Inhibitory Effect in
      Herba epimedii Using Quantitative Pattern-Activity Relationships Based on Joint
      Action Models.
AB  - Screening of bioactive components is important for modernization and quality
      control of herbal medicines, while the traditional bioassay-guided phytochemical
      approach is time-consuming and laborious. The presented study proposes a strategy
      for rapid screening of active components from herbal medicines. As a case study,
      the quantitative pattern-activity relationship (QPAR) between compounds and the
      osteoclastic inhibitory effect of Herba epimedii, a widely used herbal medicine
      in China, were investigated based on joint models. For model construction,
      standard mixtures data showed that the joint-action models are better than the
      partial least-squares (PLS) model. Then, the Good2bad value, which could reflect
      components' importance based on Monte Carlo sampling, was coupled with the joint
      action models for screening of active components. A compound (baohuoside I) and a
      component composed of compounds with retention times in the 6.9-7.9 min range
      were selected by our method. Their inhibition rates were higher than icariin, the
      key bioactive compound in Herba epimedii, which could inhibit osteoclast
      differentiation and bone resorption in a previous study. Meanwhile, the half
      maximal effective concentration, namely, EC50 value of the selected component was
      7.54 MUg/mL, much smaller than that of baohuoside I-77 MUg/mL-which indicated
      that there is synergistic action between compounds in the selected component. The
      results clearly show our proposed method is simple and effective in screening the
      most-bioactive components and compounds, as well as drug-lead components, from
      herbal medicines.

PMID- 29048400
TI  - CD10-/ALDH- cells are the sole cisplatin-resistant component of a novel ovarian
      cancer stem cell hierarchy.
AB  - It is long established that tumour-initiating cancer stem cells (CSCs) possess
      chemoresistant properties. However, little is known of the mechanisms involved,
      particularly with respect to the organisation of CSCs as stem-progenitor
      differentiated cell hierarchies. Here we aimed to elucidate the relationship
      between CSC hierarchies and chemoresistance in an ovarian cancer model. Using a
      single cell-based approach to CSC discovery and validation, we report a novel,
      four-component CSC hierarchy based around the markers cluster of differentiation
      10 (CD10) and aldehyde dehydrogenase (ALDH). In a change to our understanding of
      CSC biology, resistance to chemotherapy drug cisplatin was found to be the sole
      property of CD10-/ALDH- CSCs, while all four CSC types were sensitive to
      chemotherapy drug paclitaxel. Cisplatin treatment quickly altered the hierarchy,
      resulting in a three-component hierarchy dominated by the cisplatin-resistant
      CD10-/ALDH- CSC. This organisation was found to be hard-wired in a long-term
      cisplatin-adapted model, where again CD10-/ALDH- CSCs were the sole cisplatin
      resistant component, and all CSC types remained paclitaxel-sensitive. Molecular
      analysis indicated that cisplatin resistance is associated with inherent- and
      adaptive-specific drug efflux and DNA-damage repair mechanisms. Clinically, low
      CD10 expression was consistent with a specific set of ovarian cancer patient
      samples. Collectively, these data advance our understanding of the relationship
      between CSC hierarchies and chemoresistance, which was shown to be CSC- and drug
      type specific, and facilitated by specific and synergistic inherent and adaptive
      mechanisms. Furthermore, our data indicate that primary stage targeting of CD10
      /ALDH- CSCs in specific ovarian cancer patients in future may facilitate
      targeting of recurrent disease, before it ever develops.

PMID- 29048401
TI  - p53 dynamics orchestrates with binding affinity to target genes for cell fate
      decision.
AB  - Emerging evidence support that temporal dynamics is pivotal for signaling
      molecules in orchestrating smart responses to diverse stimuli. p53 is such a
      signaling molecule that employs temporal dynamics for the selective activation of
      downstream target genes and ultimately for cell fate decision. Yet how this fine
      tuned p53 machinery is quantitatively decoded remains largely unclear. Here we
      report a quantitative mechanism defining how p53 dynamics orchestrates with
      binding affinity to target genes for cell fate decision. Treating cells with a
      genotoxic drug doxorubicin at various doses and durations, we found that a mild
      and prolonged challenge triggered sequential p53 pulses and ultimately resulted
      in a terminal pulse enacting apoptosis in a comparable rate with that induced by
      an acute and high-dose treatment. To transactivate proapoptotic genes and
      thereafter executing apoptosis, p53 must exceed a certain threshold and
      accumulate for sufficient time at levels above it. Effective cumulative levels
      above the threshold, defined as E?p53, but not the total accumulation levels of
      p53, precisely discriminate survival and apoptotic cells. p53 accumulation below
      this threshold, even with prolonging time to reach a total level comparable to
      that from the accumulation over the threshold, could not transactivate
      proapoptotic genes to which the binding affinity of p53 is lower than that of
      proarrest genes, and this property is independent of dynamic features. Our
      findings indicate that the dynamic feature per se does not directly control cell
      fate, but rather it orchestrates with the binding affinity to target genes to
      confer an appropriate time window for cell fate choice. Our study provides a
      quantitative mechanism unifying p53 dynamics and binding affinity to target
      genes, providing novel insights to understand how p53 can respond quantitatively
      to chemotherapeutic drugs, and guiding the design of metronomic regimens for
      chemotherapeutic drugs.

PMID- 29048402
TI  - miR-3656 expression enhances the chemosensitivity of pancreatic cancer to
      gemcitabine through modulation of the RHOF/EMT axis.
AB  - The highly refractory nature of pancreatic cancer (PC) to chemotherapeutic drugs
      is one of the key reasons contributing to the poor prognosis of this disease.
      MicroRNAs (miRNAs) are key regulators of gene expression and have been implicated
      in a variety of processes from cancer development through to drug resistance.
      Herein, through miRNA profiling of gemcitabine-resistant (GR) and parental PANC-1
      cell lines, we found a consistent reduction of miR-3656 in GR PANC-1 cells. miR
      3656 overexpression enhanced the antitumor effect of gemcitabine, whereas
      silencing of miR-3656 resulted in the opposite effect. By performing mechanistic
      studies using both in vitro and in vivo models, we found that miR-3656 could
      target RHOF, a member of the Rho subfamily of small GTPases, and regulate the EMT
      process. Moreover, enforced EMT progression via TWIST1 overexpression compromised
      the chemotherapy-enhancing effects of miR-3656. Finally, we found significantly
      lower levels of miR-3656 and higher levels of RHOF in PC tissues compared with
      adjacent noncancerous pancreatic tissues, and this was also associated with poor
      PC patients' prognosis. Taken together, our results suggest that the miR
      3656/RHOF/EMT axis is an important factor involved in regulating GR in PC, and
      highlights the potential of novel miR-3656-based clinical modalities as a
      therapeutic approach in PC patients.

PMID- 29048403
TI  - Prenatal factors associated with neonatal survival of infants with congenital
      chylothorax.
AB  - OBJECTIVES: Congenital chylothorax is a rare disease and prognostic factors are
      key element in properly informing parents. This study aimed at determining the
      prenatal factors associated with neonatal survival in a cohort of liveborn
      infants with congenital chylothorax. STUDY DESIGN: Observational monocentric
      cohort study including all liveborn neonates consecutively admitted for
      congenital chylothorax. RESULTS: Neonatal mortality was 32% (16/50). Prematurity
      (or birth weight), persistence of hydrops at birth and the absence of
      thoracoamniotic shunt procedure were significantly associated with mortality,
      whereas prenatal diagnosis of pleural effusion, side of pleural effusion, hydrops
      fetalis and amniodrainage were not. In case of prenatal diagnosis of hydrops
      fetalis, the reversal in utero of hydrops fetalis was significantly associated
      with survival (P=0.001). In case of thoracoamniotic shunting, the interval
      between thoracoamniotic shunting intervention and delivery was significantly
      longer for patients who survived (P=0.03). CONCLUSIONS: Thoracoamniotic shunting
      and reversal of hydrops significantly improves survival, whereas prematurity
      worsened outcome of liveborn infants with congenital chylothorax. Our data also
      suggest that the interval between thoracoamniotic shunting and birth appears to
      be crucial; the longer the interval, the more likely is the reversal of antenatal
      hydrops and neonatal survival.

PMID- 29048404
TI  - Association of unit-wide oxygen saturation target on incidence of pulmonary
      hypertension in very low birthweight premature infants.
AB  - OBJECTIVE: Assess the effect of increasing pulse oximetry targets on incidence of
      pulmonary hypertension in very low birthweight premature infants. STUDY DESIGN:
      Retrospective cohort study comparing pulmonary hypertension incidence among three
      cohorts of premature infants exposed to varying oxygen saturation targets (Cohort
      1: n=459, 1 May 2009 to 30 April 2011, 85-94%; Cohort 2: n=474, 1 May 2011 to 31
      May 2013, 88-94%; Cohort 3: n=387, 1 June 2013 to 31 May 2015, 90-95%). Subjects
      had birth weight <1500 g and gestational age 23-32 weeks. Chi-square, Kruskall
      Wallis and Anderson-Darling tests were used, as well as multivariable logistic
      regression. RESULTS: Incidence of pulmonary hypertension declined with higher
      oxygen saturation targets (19.0% Cohort 1, 7.9% Cohort 2, 9.6% Cohort 3,
      P<0.001). Other parameters were largely not different between cohorts though
      rates of chorioamnionitis and prenatal steroids increased and oxygen use, inhaled
      nitric oxide use, necrotizing enterocolitis and patent ductus arteriosus ligation
      decreased over time. CONCLUSION: Higher oxygen saturation targets for very low
      birthweight premature infants were associated with reduced rates of pulmonary
      hypertension in this retrospective cohort study.

PMID- 29048405
TI  - Cooling in neonatal hypoxic-ischemic encephalopathy: practices and opinions on
      minimum standards in the state of California.
AB  - OBJECTIVE: Although hospitals increasingly offer therapeutic hypothermia (TH),
      there is variable implementation of related services. We assessed current
      practices and opinions regarding what services should be required of centers
      providing TH in California. STUDY DESIGN: We surveyed neonatal intensive care
      unit physicians statewide regarding practices and opinions about services related
      to TH. RESULTS: Of the 50 participating centers (47% response rate), 66% offer
      TH. Most TH centers reported using: an evidence-based protocol (92%), neurology
      consultation (92%), amplitude-integrated electroencephalography (aEEG) or EEG
      (88%), magnetic resonance imagings (MRIs) interpreted by pediatric
      neuroradiologists (71%) and developmental follow-up (93%). TH centers reported
      treating a median of 11 patients annually (interquartile range (IQR) 4 to 24).
      Respondents considered it 'critical' that TH centers offer: aEEG monitoring
      (70%), MRI (69%), occupational and physical therapy (67%) and developmental
      follow-up (94%). Over 70% thought TH centers should treat a minimum volume
      annually (median=10, IQR 5 to 12). CONCLUSION: Physicians across practice
      settings in California endorsed minimum standards for TH centers to promote
      quality of care.

PMID- 29048406
TI  - Disparity in fetal growth between twin and singleton gestation: the role of
      adipokines.
AB  - OBJECTIVE: Twin pregnancies are characterized by unique pattern of attenuated
      fetal weight gain during late gestation compared with singleton gestation. The
      mechanism(s) responsible for regulating twin growth has not yet elucidated.
      Leptin and adiponectin are two adipocytokines implicated in metabolism and energy
      balance of fetuses, newborns and adults. Moreover, these hormones have been
      suggested to play a role in fetal growth. The objective of the study was to
      determine cord blood adiponectin and leptin in twins and singletons, with and
      without growth impairment. STUDY DESIGN: This was a case-control study. It
      included two groups of newborns, matched for gestational age and birth weight
      percentile: singleton (n=60 newborns) and twins (n=44 newborns). Adiponectin and
      leptin were determined in cord blood, and compared between the groups according
      to clinical and demographic characteristics. Non-parametric and parametric
      statistical methods were employed. RESULTS: Median adiponectin and leptin
      concentrations were lower in twins vs singletons (P<0.001 for both comparisons).
      Among small for gestational age newborns (SGA), median concentration of
      adiponectin (P=0.04), but not leptin (P=0.1), was lower in twins compared to
      singletons. In pooled analysis (singleton plus twins), cord blood adiponectin and
      leptin were strongly correlated with gestational age (P<0.001 and P=0.005,
      respectively) and birth weight (P<0.001 and P<0.001, respectively). Regression
      analysis revealed that plurality (P=0.02) was significantly and independently
      associated with cord blood adiponectin concentrations, after adjustment for
      confounding variables. Similar regression in which leptin was the independent
      variable revealed that only birth weight (P=0.01) was significantly and
      independently associated with cord blood leptin concentrations. CONCLUSIONS: Twin
      pregnancies are associated with lower cord blood concentrations of adiponectin
      and leptin compared with singleton gestations. However, only cord blood
      adiponectin, but not leptin, was lower in SGA neonates. Collectively, these data
      suggest that adiponectin may be implicated in the mechanism accounting for the
      growth disparity between twins and singletons.

PMID- 29048407
TI  - Pulse oximetry screening for critical congenital heart diseases at two different
      hospital settings in Thailand.
AB  - OBJECTIVE: To evaluate the predictive abilities of pulse oximetry screening (POS)
      for critical congenital heart disease (CRIT.CHD) at two different hospital
      settings in Thailand. STUDY DESIGN: The study was conducted in healthy newborns
      at Ramathibodi Hospital (RH), a university hospital and Maharat Nakhon Ratchasima
      Hospital (MH), a regional hospital. Positive POS was defined as oxygen saturation
      (SpO2) <95% or difference between pre- and postductal SpO2 >3%. RESULTS: Of 11
      407 live births, 10 603 (92.9%) newborns were enrolled with a follow-up rate at 1
      month of 78.3%. Incidence of CRIT.CHD (per 1000 live births) at RH and MH were
      5.7 and 2.7, respectively. POS could detect three newborns who would have had a
      missed diagnosis. Sensitivity of POS for CRIT.CHD at RH was 82.3% vs 100% at MH.
      Overall specificity was 99.9% and false-positive rate was 0.009%. Combination of
      POS and physical examination (PE) enhanced detection ability to 100% at both
      hospitals. CONCLUSION: POS combined with PE improved detection of CRIT.CHD.
      Routine POS is useful in personnel-limited settings.

PMID- 29048408
TI  - The Charlie Gard case: British and American approaches to court resolution of
      disputes over medical decisions.

PMID- 29048409
TI  - Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve
      outcomes of premature infants.
AB  - OBJECTIVE: Human milk (donor milk (DM) and/or maternal milk (MM)) feedings
      protect against late onset sepsis (LOS), necrotizing enterocolitis (NEC) and
      death. However, DM lacks many anti-infective components of MM. Therefore, we
      studied exclusive MM feedings to evaluate the full effect of human milk on
      infectious and other outcomes in premature infants. STUDY DESIGN: All infants
      born before 33 weeks postmenstrual age (PMA) who received exclusive (>95%) MM or
      exclusive preterm formula (PF) were included in this prospective investigation.
      RESULTS: Sixty-three infants (53%) received MM and 55 infants (47%) received PF.
      Both groups had similar baseline characteristics. Infants in the MM group
      achieved full enteral nutrition sooner (14+/-8 vs 19+/-15 days, P<0.03) and
      required a shorter duration of central venous lines (14+/-10 vs 22+/-21,
      P<0.005). Fewer infants in the MM group developed LOS (9 vs 19, P<0.05) and
      pneumonia (8 vs 16, P<0.05) than PF infants. Only one MM and five PF infants
      developed NEC (Bell stage ?II). Logistic regression analysis using PMA and
      prolonged rupture of membranes as covariates demonstrated an increased rate of
      NEC (odds ratio=8.85, CI=1.01 to 25.17, P=0.048) in PF infants. Periventricular
      leukomalacia (PVL) was more common in PF (4 vs 0, P=0.04) than in MM infants.
      CONCLUSION: Feedings of MM advanced more rapidly and were associated with fewer
      infections than PF. A possible protective effect of MM against PVL, not
      previously described, may be related to its immune and anti-inflammatory
      components.

PMID- 29048410
TI  - Executive functioning in low birth weight children entering kindergarten.
AB  - OBJECTIVES: Poor executive functioning is associated with life-long difficulty.
      Identification of children at risk for executive dysfunction is important for
      early intervention to improve neurodevelopmental outcomes. STUDY DESIGN: This
      study is designed to examine relationships between birthweight and executive
      functioning in US children during kindergarten. Our hypothesis was that children
      with higher birthweights would have better executive function scores. We
      evaluated data from 17506 US children from the Early Childhood Longitudinal Study
      Kindergarten 2011 cohort. Birthweight and gestational age were obtained by
      parental survey. Executive functions were directly assessed using the number
      reverse test and card sort test to measure working memory and cognitive
      flexibility, respectively. Teacher evaluations were used for additional executive
      functions. Data were analyzed using SAS to run all linear and logistical
      regressions. RESULTS: For every kilogram of birthweight, scores of working memory
      increased by 1.47 (P<0.001) and cognitive flexibility increased by 0.28 (P<0.001)
      independent of gender, gestational age, parental education, and family income.
      Low birthweight infants were 1.5 times more likely to score in the bottom 20% of
      children on direct assessment OR=1.49 (CI 1.21-1.85) and OR=1.55 (CI 1.26-1.91).
      CONCLUSIONS: Infants born low birthweight are at increased risk of poor executive
      functioning. As birthweight increases executive function scores improve, even
      among infants born normal weight. Further evaluation of this population including
      interventions and progression through school is needed.

PMID- 29048411
TI  - Early versus 6-12 week postpartum glucose tolerance testing for women with
      gestational diabetes.
AB  - OBJECTIVE: The objective of this study is to estimate the accuracy of early oral
      glucose tolerance testing (GTT), to predict impaired glucose tolerance. STUDY
      DESIGN: This was a prospective cohort study. Women received an early 75 g 2 h GTT
      between postpartum days 2-4 and again 6-12 weeks postpartum. The ability of the
      early GTT to accurately detect impaired glucose tolerance and diabetes was
      assessed by calculating sensitivity, specificity, positive predictive value (PPV)
      and negative predictive values (NPVs). The routine 6-12-week postpartum GTT was
      considered the gold standard. RESULTS: The early GTT was completed by 100% of
      subjects, whereas only 31 of 58 (53%) women returned to complete the 6-12-week
      postpartum GTT. The early GTT had modest sensitivity for impaired glucose
      tolerance (62.5%) and overt diabetes (50%). However, it had excellent specificity
      (100%), PPV (100%) and NPV (96.7%) for diabetes. The NPV for impaired glucose
      tolerance with the early GTT was 80%. CONCLUSION: Rates of 6-12 week postpartum
      GTT completion among patients with gestational diabetes is poor. Appropriate
      postpartum management may improve by using the early GTT as a screening test.

PMID- 29048412
TI  - Parental assessment of comfort in newborns affected by life-limiting conditions
      treated by a standardized neonatal comfort care program.
AB  - OBJECTIVE: To assess the perception of parents concerning the state of comfort
      maintained in their infants born with life-limiting conditions and treated by a
      standardized neonatal comfort care program. STUDY DESIGN: Participants were
      parents (n=35 families) who elected comfort care for their newborns diagnosed
      with life-limiting conditions. Standardized comfort measures including
      family/infant bonding, warmth, nutrition/hydration and pain/discomfort management
      were provided to all infants. Parents consented to receive a questionnaire with
      quantitative response options and open-ended questions. RESULTS: Forty-two
      questionnaires (26 from mothers and 16 from fathers) were collected and analyzed.
      Most parents reported that their child was treated with respect, in a caring,
      peaceful and non-invasive environment. To the question 'Do you think that overall
      your baby received comfort' mode response was 'always'. CONCLUSION: Parents of
      infants with life-limiting conditions perceive that their babies experience
      comfort as a result of the care provided by the standardized Neonatal Comfort
      Care Program.

PMID- 29048413
TI  - A practical approach to the evaluation and treatment of an infant with aplasia
      cutis congenita.
AB  - Aplasia cutis congenita (ACC) is a term describing absence of skin at birth. ACC
      is a rare cutaneous finding, often noted with no other physical abnormalities.
      The etiology of ACC varies, and there are likely several causes for its
      development. ACC can be located anywhere on the body. Its clinical appearance and
      location can alert the clinician to other potential abnormalities and
      associations. This discussion covers the diagnosis of ACC and its subtypes and
      associations in order to provide a pragmatic, clinically relevant and patient
      centered approach to evaluation and treatment.

PMID- 29048414
TI  - Constructing a relevant decision aid for parents of children with
      bronchopulmonary dysplasia.
AB  - BACKGROUND: To develop and test a decision aid for counseling parents of children
      with bronchopulmonary dysplasia (BPD).Local problem:Parental education about
      complex conditions is not standardized and communication and understanding may
      not be adequate. METHODS: Semi-structured interviews were conducted with 33
      neonatal clinicians and 12 parents of children with BPD using a qualitative
      research design. The interviews were used to identify education topics that were
      felt to be important in BPD education. These topics were then used to create a
      visual decision aid to be used in counseling sessions with parents. The decision
      aid was then used in mock counseling sessions with 15 'experienced' participants
      and 7 'naive' participants to assess its efficacy. The participants completed a
      pre and post test to assess change in knowledge as well as an 11-question Likert
      style acceptability survey. INTERVENTION: Implementation of a decision aid while
      educating parents about BPD. RESULTS: Topics identified during the interviews
      were used to create eight educational cards which included pictures, pictographs
      and statistics. Overall, participants thought the decision aid contained an
      appropriate amount of information, were easy to understand and improved their
      knowledge about BPD. Testing demonstrated a significant increase in knowledge in
      both the 'experienced' (P<0.0001) and 'naive' group (P=0.0064). CONCLUSION: A
      decision aid for parents of children with BPD may improve understanding of the
      condition and help facilitate communication between parents and doctors.

PMID- 29048415
TI  - Antenatal methadone vs buprenorphine exposure and length of hospital stay in
      infants admitted to the intensive care unit with neonatal abstinence syndrome.
AB  - OBJECTIVE: Antenatal exposure to methadone or buprenorphine often causes neonatal
      abstinence syndrome (NAS) in newborns. However, comparative effects on affected
      infants' hospital courses are inconclusive. We sought to estimate the
      relationship of antenatal exposure with methadone or buprenorphine and infants'
      length of stay among hospitalized infants with NAS. STUDY DESIGN: This was a
      retrospective cohort study of hospitalized infants with NAS with either maternal
      exposure. Eligible infants were singleton infants born ?36 weeks' gestation and
      diagnosed with NAS<7 days of age between 2011 and 2014 in the Pediatrix Clinical
      Data Warehouse. Infant with congenital anomalies and those of multiple gestation
      were excluded. RESULTS: Of 3364 eligible infants, 2202 (65%) were exposed to
      methadone and 1162 (34%) to buprenorphine. Infants exposed to buprenorphine had a
      lower rate of pharmacologic treatment for NAS (88 vs 91%, P<0.001). Median length
      of hospital stay was shorter among infants exposed to buprenorphine (21 days
      (inter-quartile range; 13-31) vs methadone (24 days (15-38), P<0.0001)). On
      multivariable Cox proportional hazard analyses, buprenorphine was associated with
      a shorter length of stay (hazard ratio (HR)=1.47 (95% confidence interval (CI):
      1.32-1.62, P<0.001) after controlling for maternal age, parity, race or
      ethnicity, prenatal care, smoking status, use of antidepressants, use of
      benzodiazepines, and infant gestational age, small for gestational age status,
      cesarean delivery, sex, out born status, type of pharmacotherapy, breast milk
      use, year and center. We observed similar results in model using infants matched
      1:1 with propensity scores for antenatal medication exposure (HR 1.39 for
      buprenorphine, CI 1.32-1.62, P<0.001). CONCLUSION: Among infants born ?36 weeks'
      gestation with NAS, antenatal buprenorphine exposure was associated with a
      decreased length of stay relative to antenatal methadone exposure.

PMID- 29048416
TI  - Increased Frequency of KRAS Mutations in African Americans Compared with
      Caucasians in Sporadic Colorectal Cancer.
AB  - OBJECTIVES: The basis for over-representation of colorectal cancer (CRC) in
      African-American (AA) populations compared with Caucasians are multifactorial and
      complex. Understanding the mechanisms for this racial disparity is critical for
      delivery of better care. Several studies have investigated sporadic CRC for
      differences in somatic mutations between AAs and Caucasians, but owing to small
      study sizes and conflicting results to date, no definitive conclusions have been
      reached. METHODS: Here, we present the first systematic literature review and
      meta-analysis investigating the mutational differences in sporadic CRC between
      AAs and Caucasians focused on frequent driver mutations (APC,TP53, KRAS,PI3CA,
      FBXW7,SMAD4, and BRAF). Publication inclusion criteria comprised sporadic CRC,
      human subjects, English language, information on ethnicity (AA, Caucasian, or
      both), total subject number >20, and information on mutation frequencies.
      RESULTS: We identified 6,234 publications. Meta-analysis for APC, TP54, FBXW7, or
      SMAD4 was not possible owing to paucity of data. KRAS mutations were
      statistically less frequent in non-Hispanic Whites when compared with AAs (odds
      ratio, 0.640; 95% confidence interval (CI): 0.5342-0.7666; P=0.0001), while the
      mutational differences observed in BRAF and PI3CA did not reach statistical
      significance. CONCLUSIONS: Here, we report the mutational patterns for KRAS,
      BRAF, and PI3CA in sporadic CRC of AAs and Caucasians in a systematic meta
      analysis of previously published data. We identified an increase in KRAS
      mutations in sporadic CRC in AAs, which may contribute to worse prognosis and
      increased mortality of CRC in AAs. Future studies investigating health-care
      disparities in CRC in AAs should control for KRAS mutational frequency.

PMID- 29048417
TI  - Pathways from autism spectrum disorder diagnosis to genetic testing.
AB  - PURPOSE: This study examined challenges faced by families and health providers
      related to genetic testing for autism spectrum disorder (ASD). METHODS: This
      qualitative study of 14 parents and 15 health providers identified an
      unstandardized three-step process for families who pursue ASD genetic testing.
      RESULTS: Step 1 is the clinical diagnosis of ASD, confirmed by providers
      practicing alone or in a team. Step 2 is the offer of genetic testing to find an
      etiology. For those offered testing, step 3 involves the parents' decision
      whether to pursue testing. Despite professional guidelines and recommendations,
      interviews describe considerable variability in approaches to genetic testing for
      ASD, a lack of consensus among providers, and questions about clinical utility.
      Many families in our study were unaware of the option for genetic testing;
      testing decisions by parents appear to be influenced by both provider
      recommendations and insurance coverage. CONCLUSION: Consideration of genetic
      testing for ASD should take into account different views about the clinical
      utility of testing and variability in insurance coverage. Ideally, policy makers
      from the range of clinical specialties involved in ASD care should revisit
      policies to clarify the purpose of genetic testing for ASD and promote consensus
      about its appropriate use.

PMID- 29048418
TI  - Recommending inclusion of HFE C282Y homozygotes in the ACMG actionable gene list:
      cop-out or stealth move toward population screening?

PMID- 29048419
TI  - A cross-sectional quantitative analysis of the natural history of Farber disease:
      an ultra-orphan condition with rheumatologic and neurological cardinal disease
      features.
AB  - PurposeFarber disease (OMIM 22800) is an ultrarare progressive multisystemic
      neurodevelopmental storage disorder caused by a deficiency of the lysosomal
      enzyme acid ceramidase (AC). Hard clinical end points for future clinical trials
      remain to be defined.MethodsWe quantitatively analyzed published cases with
      Farber disease (N = 96). The main outcome variables were survival and diagnostic
      delay. As a potential predictor of survival, the influence of residual AC enzyme
      activity was investigated. The analysis was performed in compliance with STROBE
      criteria.ResultsThe median survival period of the study population was 3 years.
      The median age at disease onset was 3 months, and the median age at diagnosis was
      17 months. The median diagnostic delay was 13.75 months. Patients with residual
      AC activity in fibroblasts at more than 5.1% of the normal level survived
      significantly longer than patients with residual AC activity below this
      threshold. In addition, higher residual AC activity was associated with a later
      onset of symptoms.ConclusionFarber disease onset is in infancy. Diagnostic delay
      is typically substantial. Our data suggest a phenotype-biomarker association with
      implications for future clinical and therapeutic trials. In the absence of a
      prospective multicenter natural-history study protocol, we believe that our
      modeling approach, based on published case descriptions, is the best and most
      timely approximation for generalizability.

PMID- 29048420
TI  - Characterization of pulmonary arteriovenous malformations in ACVRL1 versus ENG
      mutation carriers in hereditary hemorrhagic telangiectasia.
AB  - PurposePulmonary arteriovenous malformations (pAVMs) are major contributors to
      morbidity and mortality in hereditary hemorrhagic telangiectasia (HHT). Mutations
      in ENG and ACVRL1 underlie the vast majority of clinically diagnosed cases. The
      aims of this study were to characterize and compare the clinical and morphologic
      features of pAVMs between these two genotype groups.MethodsSixty-six patients
      with HHT and affected family members were included. Genotype, phenotypic data,
      and imaging were obtained from medical records. Morphologic features of pAVMs
      were analyzed using computed tomography angiography. HHT symptoms, pAVM imaging
      characteristics, frequency of procedural intervention, and HHT severity scores
      were compared between ENG and ACVRL1 genotype groups.ResultsENG mutation carriers
      were more likely than ACVRL1 mutation carriers to have pAVMs (P < 0.001) or
      multiple lesions (P = 0.03), and to undergo procedural intervention (P = 0.02).
      Additionally, pAVMs in ENG carriers were more likely to exhibit bilateral lung
      involvement and growth over time, although this did not reach statistical
      significance. The HHT severity score was significantly higher in ENG than in
      ACVRL1 (P = 0.02).ConclusionThe propensity and multiplicity of ENG-associated
      pAVMs may contribute to the higher disease severity in this genotype, as
      reflected by the HHT severity score and the frequency of interventional
      procedures.

PMID- 29048421
TI  - Recurrent variants in OTOF are significant contributors to prelingual nonsydromic
      hearing loss in Saudi patients.
AB  - PurposeHearing loss is more prevalent in the Saudi Arabian population than in
      other populations; however, the full range of genetic etiologies in this
      population is unknown. We report the genetic findings from 33 Saudi hearing-loss
      probands of tribal ancestry, with predominantly prelingual severe to profound
      hearing loss.MethodsTesting was performed over the course of 2012-2016, and
      involved initial GJB2 sequence and GJB6-D13S1830 deletion screening, with
      negative cases being reflexed to a next-generation sequencing panel with 70, 71,
      or 87 hearing-loss genes.ResultsA "positive" result was reached in 63% of
      probands, with two recurrent OTOF variants (p.Glu57* and p.Arg1792His)
      accountable for a third of all "positive" cases. The next most common cause was
      pathogenic variants in MYO7A and SLC26A4, each responsible for three "positive"
      cases. Interestingly, only one "positive" diagnosis had a DFNB1-related cause,
      due to a homozygous GJB6-D13S1830 deletion, and no sequence variants in GJB2 were
      detected.ConclusionOur findings implicate OTOF as a potential major contributor
      to hearing loss in the Saudi population, while highlighting the low contribution
      of GJB2, thus offering important considerations for clinical testing strategies
      for Saudi patients. Further screening of Saudi patients is needed to characterize
      the genetic spectrum in this population.

PMID- 29048423
TI  - Identification of cross talk between SUMOylation and ubiquitylation using a
      sequential peptide immunopurification approach.
AB  - Ubiquitin and ubiquitin-like modifiers (UBLs) such as small ubiquitin-like
      modifier (SUMO) can act as antagonists to one another by competing to occupy
      similar residues in the proteome. In addition, SUMO and ubiquitin can be coupled
      to each other at key lysine residues to form highly branched protein networks.
      The interplay between these modifications governs important biological processes
      such as double-strand break repair and meiotic recombination. We recently
      developed an approach that permits the identification of proteins that are
      modified by both SUMOylation and ubiquitylation. This protocol requires cells
      that express a mutant 6*His-SUMO3m protein that has had its C terminus modified
      from QQQTGG to RNQTGG, enabling the purification of SUMOylated peptides and their
      identification by tandem mass spectrometry (MS/MS). Cells are lysed under
      denaturing conditions, and the SUMOylated proteins are purified on nickel
      nitrilotriacetic acid (Ni-NTA) resin via the 6*His on the SUMO3m construct. After
      on-bead digestion using trypsin, ubiquitylated peptides are enriched by
      immunoprecipitation, and the flow-through from this step is subjected to anti
      SUMO immunoprecipitation. The SUMOylated peptides are fractionated on strong
      cation exchange (SCX) StageTips to enhance the coverage of the SUMO proteome. The
      ubiquitylated and SUMOylated peptides are analyzed separately by liquid
      chromatography (LC)-MS/MS and identified with MaxQuant. We demonstrate how this
      approach can be used to identify temporal changes in SUMOylated and ubiquitylated
      proteins in response to, for instance, heat shock and proteasome inhibition. The
      procedure requires 3 d when starting from cell pellets and yields >8,000 SUMO
      sites and >3,500 ubiquitin sites from 16 mg of cell extract.

PMID- 29048422
TI  - Cell-derived matrices for studying cell proliferation and directional migration
      in a complex 3D microenvironment.
AB  - 2D surfaces offer simple analysis of cells in culture, yet these often yield
      different cell morphologies and responses from those observed in vivo.
      Considerable effort has therefore been expended on the generation of more tissue
      like environments for the study of cell behavior in vitro. Purified matrix
      proteins provide a 3D scaffold that better mimics the in vivo situation; however,
      these are far removed from the complex tissue composition seen in vivo. Cell
      derived matrices (CDMs) offer a more physiologically relevant alternative for
      studying in vivo-like cell behavior in vitro. In the protocol described here,
      fibroblasts cultured on gelatin-coated surfaces are maintained in the presence of
      ascorbic acid to strengthen matrix deposition over 1-3 weeks. The resulting
      fibrillar CDMs are denuded of cells, and other cells are subsequently cultured on
      them, after which their behavior is monitored. We also demonstrate how to use
      CDMs as an in vivo-relevant reductionist model for studying tumor-stroma-induced
      changes in carcinoma cell proliferation and migration.

PMID- 29048424
TI  - Analysis of human cerebrospinal fluid monoamines and their cofactors by HPLC.
AB  - The presence of monoamines and their cofactors (the pterins and vitamin B6
      (pyridoxal phosphate (PLP))) in human cerebrospinal fluid (CSF) can be used as
      indicators of the biosynthesis and turnover of dopamine and serotonin in the
      brain. In addition, abnormalities in the CSF levels of these molecules are
      associated with various neurological diseases, including genetic diseases leading
      to dopamine and serotonin deficiency. Here, we provide a set of quantitative high
      performance liquid-chromatography (HPLC) approaches to determine CSF levels of
      monoamines and their cofactors. This protocol describes step-by-step procedures
      for CSF sample preparation for the analysis of different molecules, HPLC
      calibration and analysis, and data quantification and interpretation. Unlike
      plasma/tissue/blood samples, CSF requires minimal sample preparation: in this
      protocol, only the analysis of PLP requires mixing with trichloroacetic acid to
      release the protein-bound vitamin, centrifugation, and mixing of the supernatant
      with phosphate buffer and sodium cyanide for derivatization in alkaline
      conditions. Monoamines are analyzed by HPLC with coulometric electrochemical
      detection (ED), pterins are analyzed by HPLC with coupled coulometric
      electrochemical and fluorescence detection, and PLP is analyzed by HPLC with
      fluorescence detection. The quantification of all compounds is achieved by
      external calibration procedures, and internal quality control and standards are
      analyzed in each run. We anticipate that investigation of dopamine and serotonin
      disturbances will be facilitated by measurements of these compounds in human CSF
      and other biological samples. The estimated time for the different procedures
      primarily depends on the electrochemical detector stabilization. Overnight
      stabilization of this detector is advised, and, after that step, preanalytical
      equilibration rarely exceeds 3 h.

PMID- 29048425
TI  - Cardamonin induces ROS-mediated G2/M phase arrest and apoptosis through
      inhibition of NF-kappaB pathway in nasopharyngeal carcinoma.
AB  - Cardamonin has been demonstrated to have an inhibitory effect in many cancers,
      but its underlying mechanism remains elusive. Here, we studied, for the first
      time, the mechanism of cardamonin-induced nasopharyngeal carcinoma cell death
      both in vitro and in vivo. In our study, we showed that cardamonin inhibited
      cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis via
      accumulation of ROS. NF-kappaB activation was involved in breaking cellular redox
      homeostasis. Therefore, our results provided new insight into the mechanism of
      the antitumor effect of cardamonin, supporting cardamonin as a prospective
      therapeutic drug in nasopharyngeal carcinoma by modulating intracellular redox
      balance.

PMID- 29048427
TI  - HDAC6 inhibition by tubastatin A is protective against oxidative stress in a
      photoreceptor cell line and restores visual function in a zebrafish model of
      inherited blindness.
AB  - Retinal diseases, such as hereditary retinitis pigmentosa and age-related macular
      degeneration, are characterized by the progressive loss of photoreceptors.
      Histone deacetylase 6 (HDAC6) is considered as a stress surveillance factor and a
      potential target for neuroprotection and regeneration. Overexpression of HDAC6
      has been connected to neurodegenerative disorders, and its suppression may
      provide protection. Here we show that HDAC6 is constitutively present in the
      mouse retina, and in the cone-like mouse cell line 661W. In 661W cells HDAC6
      inhibition by the specific inhibitor tubastatin A (TST) led to the acetylation of
      alpha-tubulin, which is a major substrate for HDAC6. After oxidative stress,
      exerted by hydrogen peroxide, TST promoted cell survival and the upregulation of
      heat-shock proteins HSP70 and HSP25 by activation of heat-shock transcription
      factor 1. Furthermore, in response to oxidative stress the redox regulatory
      protein peroxiredoxin 1 (Prx1) was modulated in 661W cells by HDAC6 inhibition.
      The peroxide reducing activity of Prx1 is dependent on its acetylation, which is
      mediated by HDAC6. Pre-incubation with TST prevented the inactivation of Prx1 and
      its preserved activity may exert protective effects in photoreceptor cells. To
      determine whether TST treatment has a therapeutic effect on visual function, the
      dyeucd6 zebrafish model of inherited sight loss was utilized. Zebrafish have
      developed as a suitable model system for pharmacological testing. In vivo
      application of TST caused the hyperacetylation of alpha-tubulin, indicating that
      HDAC6 is active in this model. Furthermore, TST was sufficient to rescue visual
      function and retinal morphology. Hence, HDAC6 inhibition and the regulation of
      peroxiredoxin activity may play a significant role in protecting retinal cells
      and in particular photoreceptors, which are exposed to high levels of reactive
      oxygen species derived from oxidative stress-induced injuries.

PMID- 29048426
TI  - FGF1 protects neuroblastoma SH-SY5Y cells from p53-dependent apoptosis through an
      intracrine pathway regulated by FGF1 phosphorylation.
AB  - Neuroblastoma, a sympathetic nervous system tumor, accounts for 15% of cancer
      deaths in children. In contrast to most human tumors, p53 is rarely mutated in
      human primary neuroblastoma, suggesting impaired p53 activation in neuroblastoma.
      Various studies have shown correlations between fgf1 expression levels and both
      prognosis severity and tumor chemoresistance. As we previously showed that
      fibroblast growth factor 1 (FGF1) inhibited p53-dependent apoptosis in neuron
      like PC12 cells, we initiated the study of the interaction between the FGF1 and
      p53 pathways in neuroblastoma. We focused on the activity of either extracellular
      FGF1 by adding recombinant rFGF1 in media, or of intracellular FGF1 by
      overexpression in human SH-SY5Y and mouse N2a neuroblastoma cell lines. In both
      cell lines, the genotoxic drug etoposide induced a classical mitochondrial p53
      dependent apoptosis. FGF1 was able to inhibit p53-dependent apoptosis upstream of
      mitochondrial events in SH-SY5Y cells by both extracellular and intracellular
      pathways. Both rFGF1 addition and etoposide treatment increased fgf1 expression
      in SH-SY5Y cells. Conversely, rFGF1 or overexpressed FGF1 had no effect on p53
      dependent apoptosis and fgf1 expression in neuroblastoma N2a cells. Using
      different FGF1 mutants (that is, FGF1K132E, FGF1S130A and FGF1S130D), we further
      showed that the C-terminal domain and phosphorylation of FGF1 regulate its
      intracrine anti-apoptotic activity in neuroblastoma SH-SY5Y cells. This study
      provides the first evidence for a role of an intracrine growth factor pathway on
      p53-dependent apoptosis in neuroblastoma, and could lead to the identification of
      key regulators involved in neuroblastoma tumor progression and chemoresistance.

PMID- 29048429
TI  - Different death destinies: relative apoptosis sensitivity shapes the human
      effector CD8+ T-cell response derived from distinct memory subsets.

PMID- 29048428
TI  - Dual role of DR5 in death and survival signaling leads to TRAIL resistance in
      cancer cells.
AB  - Besides its tumor-selective apoptotic activity, tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) promotes pro-survival, proliferative or
      migratory signaling (NF-kappaB, PI3K/Akt, MAPK and JNK; referred to as 'non
      apoptotic' cascades). Indeed, apoptosis and non-apoptotic signaling can be
      activated in clonal populations of cancer cells in response to treatment and, as
      a result, only a part of the initial cellular population dies while a fraction
      survives and develops resistance to TRAIL-induced apoptosis (referred to as
      'fractional survival'). Notably, the molecular characterization of the protein
      platforms streaming into tumoricidal versus tumor-promoting cascades that control
      fractional survival remained elusive. Here we demonstrate that, in the context of
      DR4-DR5-DcR2 hetero-oligomeric complexes, a single death receptor (DR5) suffices
      to assemble composite plasma membrane-proximal pro-apoptotic/pro-survival
      platforms that propagate TRAIL signaling to both death and survival pathways in
      clonal populations of cancer cells. Moreover, we show that while all members of
      TRAIL-induced complexes support survival, none of them acted exclusively pro
      apoptotic. Indeed, key apoptotic proteins as FADD and procaspase-8 were also
      involved in transducing non-apoptotic signaling in response to this cytokine.
      Collectively, this study reveals the Janus faces of DR5, and the contributions of
      other death complex components in fractional survival that foster the generation
      of resistance. Our data highlight a new level of complexity in TRAIL signaling
      and point to an improved therapeutic rationale in view of hitherto disappointing
      results.

PMID- 29048430
TI  - Amlexanox, a selective inhibitor of IKBKE, generates anti-tumoral effects by
      disrupting the Hippo pathway in human glioblastoma cell lines.
AB  - Glioblastoma multiforme (GBM) is the most prevalent form of malignant brain
      tumor. Amlexanox, a novel compound, has been shown to have anti-cancer potential.
      In this study, the anti-tumoral effects and the underlying mechanisms of
      amlexanox were investigated. Amlexanox significantly suppressed proliferation and
      invasion and induced apoptosis in glioblastoma cells. Furthermore, we found that
      amlexanox altered the protein expression of the Hippo pathway by downregulating
      IKBKE. Our data indicates that IKBKE directly targets LATS1/2 and induces
      degradation of LATS1/2, thereby inhibiting the activity of the Hippo pathway. In
      vivo results further confirmed the tumor inhibitory effect of amlexanox via the
      downregulation of IKBKE, and amlexanox induced no apparent toxicity.
      Collectively, our studies suggest that amlexanox is a promising therapeutic agent
      for the treatment of GBM.

PMID- 29048431
TI  - HSPB1 facilitates ERK-mediated phosphorylation and degradation of BIM to
      attenuate endoplasmic reticulum stress-induced apoptosis.
AB  - BIM, a pro-apoptotic BH3-only protein, is a key regulator of the intrinsic (or
      mitochondrial) apoptosis pathway. Here, we show that BIM induction by endoplasmic
      reticulum (ER) stress is suppressed in rat PC12 cells overexpressing heat shock
      protein B1 (HSPB1 or HSP27) and that this is due to enhanced proteasomal
      degradation of BIM. HSPB1 and BIM form a complex that immunoprecipitates with p
      ERK1/2. We found that HSPB1-mediated proteasomal degradation of BIM is dependent
      on MEK-ERK signaling. Other studies have shown that several missense mutations in
      HSPB1 cause the peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease, which
      is associated with nerve degeneration. Here we show that cells overexpressing CMT
      related HSPB1 mutants exhibited increased susceptibility to ER stress-induced
      cell death and high levels of BIM. These findings identify a novel function for
      HSPB1 as a negative regulator of BIM protein stability leading to protection
      against ER stress-induced apoptosis, a function that is absent in CMT-associated
      HSPB1 mutants.

PMID- 29048432
TI  - Silencing FLI or targeting CD13/ANPEP lead to dephosphorylation of EPHA2, a
      mediator of BRAF inhibitor resistance, and induce growth arrest or apoptosis in
      melanoma cells.
AB  - A majority of patients with BRAF-mutated metastatic melanoma respond to therapy
      with BRAF inhibitors (BRAFi), but relapses are common owing to acquired
      resistance. To unravel BRAFi resistance mechanisms we have performed gene
      expression and mass spectrometry based proteome profiling of the sensitive
      parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell
      lines with induced BRAFi resistance. Increased expression of two novel resistance
      candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was
      observed in the BRAFi-resistant daughter cell lines. In addition, increased
      levels of the previously reported resistance mediators, receptor tyrosine kinase
      ephrine receptor A2 (EPHA2) and the hepatocyte growth factor receptor MET were
      also identified. The expression of these proteins was assessed in matched tumor
      samples from melanoma patients obtained before BRAFi and after disease
      progression. MET was overexpressed in all progression samples while the
      expression of the other candidates varied between the individual patients.
      Targeting CD13/ANPEP by a blocking antibody induced apoptosis in both parental
      A375- and BRAFi-resistant daughter cells as well as in melanoma cells with
      intrinsic BRAFi resistance and led to dephosphorylation of EPHA2 on S897,
      previously demonstrated to cause inhibition of the migratory capacity. AKT and
      RSK, both reported to induce EPHA2 S897 phosphorylation, were also
      dephosphorylated after inhibition of CD13/ANPEP. FLI1 silencing also caused
      decreases in EPHA2 S897 phosphorylation and in total MET protein expression. In
      addition, silencing of FLI1 sensitized the resistant cells to BRAFi. Furthermore,
      we show that BRAFi in combination with the multi kinase inhibitor dasatinib can
      abrogate BRAFi resistance and decrease both EPHA2 S897 phosphorylation and total
      FLI1 protein expression. This is the first report presenting CD13/ANPEP and FLI1
      as important mediators of resistance to BRAF inhibition with potential as drug
      targets in BRAFi refractory melanoma.

PMID- 29048433
TI  - TMEM74 promotes tumor cell survival by inducing autophagy via interactions with
      ATG16L1 and ATG9A.
AB  - Autophagy is a highly inducible system of intracellular degradation that occurs
      in lysosomes or vacuoles. Transmembrane 74 (TMEM74) has been shown to induce
      autophagy. However, the mechanism by which TMEM74 stimulates autophagy and the
      impacts of TMEM74-induced autophagy on tumor cell survival remain unclear. In
      this study, TMEM74 was shown to increase the autophagic flux process in different
      tumor cell lines. Further investigations revealed that TMEM74 interacts with
      ATG16L1 and ATG9A. Moreover, distinctive from the common autophagy models, it is
      found that TMEM74-related autophagy is independent of BECN1/PI3KC3 complex and
      ULK1, and TMEM74 may initiate and promote autophagy directly via interactions
      with ATG16L1 and ATG9A responsible for the nucleation and elongation
      respectively. Considering the ultimate outcome of TMEM74-induced autophagy in
      tumor cells, TMEM74-triggered autophagy induces a pro-survival effect on tumor
      cells, particularly cells under metabolic stress, consistent with alteration of a
      series of signal pathways. Intriguingly, TMEM74 itself can be downregulated
      through the autophagic process, which indicates that a potential self-regulatory
      loop exists so as to maintain an appropriate level of autophagy, avoiding
      excessive autophagy to commit tumor cells to death. According to the clinical
      database analysis, the high expression of TMEM74 significantly shortens the
      surviving periods of patients in several specific cancers indicating that TMEM74
      itself can be treated as an effective potential target with clinical values to
      prolong surviving periods of cancer patients in the future. In conclusion, our
      study reveals a new mechanism by which autophagy is stimulated by a novel
      positive modulator through a unique pathway and demonstrates a novel connection
      between autophagy and cell survival, which undoubtedly serves to broaden our
      understanding of autophagy.

PMID- 29048435
TI  - The low-temperature dynamic crossover in the dielectric relaxation of ice Ih.
AB  - Based on the idea of defect migration as the principal mechanism in the
      dielectric relaxation of ice Ih, the concept of low-temperature dynamic crossover
      was proposed. It is known that at high temperatures, the diffusion of Bjerrum and
      ionic defects is high and their movement may be considered to be independent.
      Simple switching between these two mechanisms leads to a dynamic crossover at
      ~235 K. By introducing coupling between the Bjerrum and ionic defects, it is
      possible to describe the smooth bend in the relaxation time at low temperatures
      in ice Ih. However, because the mobility of Bjerrum orientation defects slows
      down at low temperatures, they may create blockages for proton hopping. The
      trapping of ionic defects by L-D defects for a long period of time leads to an
      increase in the relaxation time and causes a low-temperature crossover. This
      model was validated by experimental dielectric measurements using various
      temperature protocols.

PMID- 29048434
TI  - Common microRNA-mRNA interactions exist among distinct porcine iPSC lines
      independent of their metastable pluripotent states.
AB  - Previous evidences have proved that porcine-induced pluripotent stem cells
      (piPSCs) could be induced to distinctive metastable pluripotent states. This
      raises the issue of whether there is a common transcriptomic profile existing
      among the piPSC lines at distinctive state. In this study, we performed conjoint
      analysis of small RNA-seq and mRNA-seq for three piPSC lines which represent LIF
      dependence, FGF2 dependence and LFB2i dependence, respectively. Interestingly, we
      found there are 16 common microRNAs which potentially target 13 common mRNAs
      among the three piPSC lines. Dual-luciferase reporter assay validated that miR
      370, one of the 16 common microRNAs, could directly target the 3'UTR of LIN28A.
      When the differentiation occurred, miR-370 could be activated in piPSCs and
      switched off the expression of LIN28A. Ectopic expression of miR-370 in piPSCs
      could reduce LIN28A expression, decrease the alkaline phosphatase activity, slow
      down the proliferation, and further cause the downregulation of downstream
      pluripotent genes (OCT4, SOX2, NANOG, SALL4 and ESRRB) and upregulation of
      differentiation relevant genes (SOX9, JARID2 and JMJD4). Moreover, these
      phenotypes caused by miR-370 could be rescued by overexpressing LIN28A.
      Collectively, our findings suggest that a set of common miRNA-mRNA interactions
      exist among the distinct piPSC lines, which orchestrate the self-renewal and
      differentiation of piPSCs independent of their metastable pluripotent states.

PMID- 29048436
TI  - Supramolecular assembly of fluorogenic glyco-dots from perylenediimide-based
      glycoclusters for targeted imaging of cancer cells.
AB  - Supramolecular self-assembly between perylenediimide-based glycoclusters and a
      red-emitting fluorophore produces structurally uniform and stable glyco-dots
      amenable to targeted fluorogenic imaging of liver and triple-negative breast
      cancer cells.

PMID- 29048437
TI  - Photo-induced interfacial electron transfer of ZnO nanocrystals to control
      supramolecular assembly in water.
AB  - Herein, we show how the inherent light-induced redox properties of semiconducting
      nanocrystals (NCs) can be utilized for the photo-driven reversible modulation of
      dynamic supramolecular systems formed at their interfaces that, on their own, do
      not respond to light. This was achieved by the unprecedented combination of
      photoactive zinc oxide NCs (ZnO NCs) with a host-guest chemistry of
      cucurbit[8]uril (CB[8]) providing a route to the semiconductor-assisted light
      modulation of supramolecular assemblies (SALSA), here mediated by the photo
      generation of viologen radical cations (MV+) at the NC corona and their further
      dimerization enhanced by CB[8] macrocycles. The reported SALSA strategy was
      successfully applied for light-controlled reversible assembly processes at NC
      interfaces enabling light-triggered release of guest molecules from surface
      confined discrete CB[8] host-guest complexes.

PMID- 29048438
TI  - The mixed-ligand strategy to assemble a microporous anionic metal-organic
      framework: Ln3+ post-functionalization, sensors and selective adsorption of dyes.
AB  - A unique microporous anionic metal-organic framework, namely
      [Zn2(btb)2(bbis)](Me2NH2)2.6DMF (1), has been synthesized and structurally
      characterized [bbis = bis(4-benzylimidazol-ylphenyl)sulfone and H3btb = 4,4',4''
      benzene-1,3,5-triyltribenzoic acid]. This compound exhibits a 4-fold
      interpenetrated anionic framework with ins topology. The post-synthetic cation
      exchange of 1 with Eu3+, Tb3+, Dy3+ and Sm3+ afforded lanthanide(iii)-loaded
      materials. Eu3+@1 and Tb3+@1 can be used as the potential luminescent probes in
      nitrobenzene. The adsorption behavior of 1 towards organic dyes was investigated,
      revealing rapid and selective separation of methylene blue.

PMID- 29048439
TI  - Advancing porphyrin's biomedical utility via supramolecular chemistry.
AB  - Porphyrins are organic heterocyclic macrocycles with photophysical properties
      well-suited for clinical phototherapy and cancer imaging. However, their wider
      application in the clinical management of disease is barred by poor aqueous
      solubility, bioavailability, tumour accumulation and skin phototoxicity. These
      limitations instigated the development of supramolecular platforms that improved
      porphyrin pharmacokinetics and tumour-homing. The supramolecular formulation of
      porphyrins also facilitates single agent-mediated deeper tissue photoactivation,
      extended imaging and theranostic multimodality, and synergistic application of
      multiple therapies. Supramolecular porphyrin structures can overcome additional
      limitations of porphyrin-mediated photodynamic therapy (PDT), including low
      depths of tissue penetration that restrict PDT to superficial lesions, inability
      to treat hypoxic tumours, and incomplete tumour damage. In this review, we
      discuss the photophysical properties of porphyrins, and overview the clinically
      relevant advantages and challenges arising from their incorporation within
      supramolecular platforms. Specifically, fundamentals underlying the ability of
      these platforms to ameliorate passive and active porphyrin delivery to tumours,
      achieve deeper tissue PDT via red-shifted porphyrin Q-bands, energy transfer and
      sonodynamic effects, and enable new porphyrin-mediated theranostics and
      synergistic therapeutic capabilities will be explained and exemplified with
      seminal and cutting-edge in vivo studies.

PMID- 29048443
TI  - Enhancement of photoelectrochemical oxidation by an amorphous nickel boride
      catalyst on porous BiVO4.
AB  - This paper describes an amorphous nickel boride (NiB) electrocatalyst loaded on
      porous bismuth vanadate (BiVO4) with high activity for oxygen evolution in
      photoelectrochemical water oxidation. The NiB-decorated BiVO4 photoanode exhibits
      an onset potential of 0.25 V versus the reversible hydrogen electrode (vs. RHE)
      and a photocurrent of 3.47 mA cm-2 at 1.23 V vs. RHE under simulated 100 mW cm-2
      irradiation.

PMID- 29048444
TI  - Substoichiometric ribose methylations in spliceosomal snRNAs.
AB  - Sequencing-based profiling of ribose methylations is a new approach that allows
      for experiments addressing dynamic changes on a large scale. Here, we apply such
      a method to spliceosomal snRNAs present in human whole cell RNA. Analysis of
      solid tissue samples confirmed all previously known sites and demonstrated close
      to full methylation at almost all sites. Methylation changes were revealed in
      biological experimental settings, using T cell activation as an example, and in
      the T cell leukemia model, Jurkat cells. Such changes could impact the dynamics
      of snRNA interactions during the spliceosome cycle and affect mRNA splicing
      efficiency and splicing patterns.

PMID- 29048448
TI  - Exposure to individual and multiple carcinogenic metals during paediatric age: an
      experience from an Italian urban scenario.
AB  - BACKGROUND: Exposure to single and multiple carcinogenic metals and/or semimetals
      represents a major environmental risk factor for public health. In particular,
      children are more susceptible to environmental pollutants than adults, but
      specific studies are still limited. The aims of the present study were: 1) to
      trace the exposure and co-exposure profiles to eight known or suspected
      carcinogenic metals and semimetals (As, Be, Cd, Co, Cr, Ni, Pb, and Sb); and: 2)
      to evaluate the influence of some possible interfering/confounding factors on the
      exposure to these elements during childhood. STUDY DESIGN: Cross-sectional study.
      METHODS: We recruited 159 healthy Italian children attending a primary school of
      the urban area of Rome, Italy. Selected metals were determined by inductively
      coupled plasma mass spectrometry on urinary samples collected at the end of a
      "typical" day (one sample for each child), while information about possible
      confounding/interfering factors were collected via questionnaires. RESULTS: The
      great part of the studied children resulted co-exposed to the monitored metals:
      83.2%, 69.2%, 51.0% and 29.3% of the participants were concurrently exposed to at
      least two, three, four and five trace elements, respectively. Gender was the only
      one among the investigated variable that significantly influenced the co
      exposure, with females resulting at lower risk (OR = 0.392; 95 IC = 0.156 -
      0.989; p < 0.047). CONCLUSIONS: Given the importance of protecting child's health
      and the risks related to the exposure to carcinogenic metals, especially when
      they occur simultaneously, other researches in this field are strongly
      recommended.

PMID- 29048449
TI  - Emergency Medical Service Information System:the ARES 118 experience.
AB  - BACKGROUND: In this paper we describe ARES 118, the prehospital Emergency Medical
      Service of the Region Lazio, Italy, focusing on its data system used to populate
      a data warehouse and to create ad hoc reports. ARES 118 is a regional public mono
      specialized health company, established in 2004, that manages the emergency care
      throughout the Region Lazio. METHODS: Being a peculiar company in its kind, and
      being the first experience of this kind in Italy, ARES 118 has begun to equip
      itself, in an autonomous way, with a corporate information system, starting from
      what already existed as data collection from the individual provincial operating
      Centers and then by activating a unique information system at a regional and
      company level by deploying a data warehouse. All operations were carried out
      using open source software. RESULTS: Currently, ARES 118 is equipped with a
      business information system that enables data collection with its storage,
      management and processing of the same in fairly and easy way. The system allows
      the production of specific reports and measures modulated on the user requests in
      order to highlight the different aspects of the activity. CONCLUSIONS: The
      production of ad hoc reports, with the possibility of developing specific
      indicators, allows the identification and analysis of critical areas/processes in
      order to implement any corrective actions and monitor the effectiveness of the
      sam.

PMID- 29048447
TI  - Strategies for Disease Prevention and Health Promotion in Urban Areas: The Erice
      50 Charter.
AB  - The Erice 50 Charter titled "Strategies for Diseases Prevention and Health
      Promotion in Urban Areas" was unanimously approved at the conclusion of the 50th
      Residential Course "Urban Health. Instruments for promoting health and for
      assessing hygienic and sanitary conditions in urban areas", held from 29th March
      to 2nd April 2017 in Erice, at the "Ettore Majorana" Foundation and Centre for
      Scientific Culture and promoted by the International School of Epidemiology and
      Preventive Medicine "G. D'Alessandro" and the Study Group "Building Hygiene" of
      the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI). At
      the conclusion of the intense learning experience during the Course, with more
      than 20 lectures, workshops and long-lasting discussions between Professors and
      Students, the participants identified the major points connecting urban features
      and Public Health, claiming the pivotal role of urban planning strategies for the
      management of Diseases Prevention and Health Promotion activities. The Erice 50
      Charter is configured as a Decalogue for Healthy Cities and as a Think Tank for
      designing effective strategic actions and best practices to develop urban
      regeneration interventions and improve the urban quality of contemporary cities.
      The Decalogue is structured into the following key strategic objectives: 1.
      Promoting urban planning interventions that address citizens towards healthy
      behaviours; 2. Improving living conditions in the urban context; 3. Building an
      accessible and inclusive city, with a special focus on the frail population; 4.
      Encouraging the foundation of resilient urban areas; 5. Supporting the
      development of new economies and employment through urban renewal interventions;
      6. Tackling social inequalities; 7. Improving stakeholders' awareness of the
      factors affecting Public Health in the cities; 8. Ensuring a participated urban
      governance; 9. Introducing qualitative and quantitative performance tools,
      capable of measuring the city's attitude to promote healthy lifestyles and to
      monitor the population's health status; 10. Encouraging sharing of knowledge and
      accessibility to informations. Finally, all the participants underlined that a
      multidisciplinary team, composed of Physicians specialized in Hygiene, Preventive
      Medicine, Public Health and Technicians as Architects, Urban planners and
      Engineers, is needed to deepen the research topic of Urban Health.

PMID- 29048450
TI  - Aerobiological monitoring and mapping of Ambrosia plants in the province of Parma
      (northern Italy, southern Po valley), a useful tool for targeted preventive
      measures.
AB  - BACKGROUND: Ambrosia is an annual anemophilous weed producing allergenic pollen
      affecting public health in European countries. In Italy, the most infested region
      is Lombardy where, in some areas, it is the major cause of hay fever. In the
      Parma district, until 2007, Ambrosia seemed to be very rare, despite an observed
      increase of Seasonal Pollen Index (SPI), of pollen peak value and of asthma among
      ragweed sensitized patients. The aims of this study were to calculate ragweed
      pollen season and trends from 1996 to 2015, to assess the relationships between
      pollen season characteristics and selected meteorological data, to map plants in
      the territory and to evaluate the presence of beetle Ophraella communa
      (Ophraella), known as an eater of Ambrosia leaves. METHODS: The following
      pollination parameters: start, end, duration, peak concentration date, peak
      values, SPI and the following climatic parameters: temperature, relative
      humidity, rainfall, were analyzed. The ragweed plants sites were mapped and the
      presence of Ophraella was assessed during naturalistic activities. RESULTS:
      Significant SPI and pollen peak value increase until 2011 were observed, but
      recently, 2012-2015 vs 2009-2011, a strong reduction (about 50%) of these
      parameters was observed. The spring average air temperature increased
      significantly. The results of the correlation analysis showed Ambrosia season
      characteristics significantly related. We identified the sites source of
      Ambrosia, even downtown at the confluence between Parma and Baganza rivers.
      Ophraella was observed for the first time in 2014. CONCLUSIONS: The results
      showed the spread of ragweed plants over the territory and the risk of allergy
      increase that ragweed could cause. It remains to evaluate the role of the
      Ophraella in the reduction of Ambrosia pollen concentration. It is important to
      consider the potential risk Ophraella may represent for sunflower and other
      taxonomically related crop plants and other native and exotic species. The lack
      of initiatives by the Health Authorities to prevent and to contrast the spread of
      Ambrosia in the Parma area could cause public health consequences and an increase
      in health expenditures.

PMID- 29048452
TI  - Development of the laboratory prototype "CavyPool" for assessing treatments and
      materials for swimming pools.
AB  - BACKGROUND: Hygiene and surveillance in swimming pools are established by WHO
      Guidelines and national laws. Progress in water management and pool construction
      is revolutionizing the field, introducing new materials, systems, disinfection
      procedures or monitoring markers. Innovation advances challenge the upgrading of
      safety and quality in pools and the appropriate implementation of guidelines.
      STUDY DESIGN: In order to provide a device for laboratory test, a prototype was
      realized and applied to study and compare swimming pool materials and treatments.
      METHODS: A pool scale-model was engineered and evaluated by computational fluid
      dynamics algorithms. An automated real time monitoring assured steady state.
      Critical control points along the water circuit were made accessible to allow the
      placing of different biocides or water sampling. Simulations were safely
      performed in a standard hood. Materials for pool surfaces and pipelines were
      evaluated for biofilm formation under different disinfection conditions. Adherent
      microorganisms were assayed by mfDNA analysis using real time PCR. RESULTS: The
      prototype reached the steady state within 5-25 hours under different conditions,
      showing chemical, physical and fluid-dynamic stability. A method was optimized
      for testing materials showing their different response to biofilm induction.
      Several innovative PVC samples displayed highest resistance to bacterial
      adhesion. CONCLUSIONS: A device and method was developed for testing swimming
      pool hygienic parameters in laboratory. It allowed to test materials for pools
      hygiene and maintenance, including biofilm formation. It can be applied to
      simulate contaminations under different water treatments or disinfection
      strategies. It may support technical decisions and help policymakers in acquiring
      evidences for comparing or validating innovative solutions.

PMID- 29048453
TI  - Bologna Process and Basic Nursing Education in 21 European Countries.
AB  - BACKGROUND: The Bologna Process and the Directives of the European Union have had
      a profound impact on nursing education in Europe. The aim of this study was to
      identify the similarities and differences within nursing education framework at
      entry level in 2014 in European countries. METHODS: A questionnaire was devised
      by the researchers and distributed via e-mail to the nursing associations/nursing
      regulatory bodies of 30 European countries. Data were collected from January to
      May 2014. RESULTS: Responses were received from 21 European Countries. Results
      indicated that while a completion of 12 years of general education was a
      requirement to access nursing education in almost all respondent countries, other
      admission requirements differed between countries. Nursing courses were offered
      mostly by Faculties of Nursing and Faculties of Health Sciences (in higher
      education Institutions) and lecturers and management staff were mainly nurses.
      The results indicated significant different educational requirements for nurse
      educators. A foreign language was mandatory in half of the respondent countries.
      Nursing profession was represented at government level in just over half of the
      respondent countries, often with a Directorate position. CONCLUSIONS: The Bologna
      Process has helped harmonise initial nursing education in Europe but clear
      standards for nursing education need to be set up. Therefore, the research about
      the influence of the Bologna process on the development of the nursing profession
      should be further encouraged.

PMID- 29048451
TI  - Definition of criteria and indicators for the prevention of Healthcare-Associated
      Infections (HAIs) in hospitals for the purposes of Italian institutional
      accreditation and performance monitoring.
AB  - BACKGROUND: Healthcare-associated infections (HAIs) are an important issue in
      terms of quality of care. HAIs impact patient safety by contributing to higher
      rates of preventable mortality and prolonged hospitalizations. In Italy, analysis
      of the currently available accreditation systems shows a substantial
      heterogeneity of approaches for the prevention and surveillance of HAIs in
      hospitals. The aim of the present study is to develop and propose the use of a
      synthetic assessment tool that could be implemented homogenously throughout the
      nation. METHODS: An analysis of nine international and of the 21 Italian regional
      accreditation systems was conducted in order to identify requirements and
      indicators implemented for HAI prevention and control. Two relevant reviews on
      this topic were further analyzed to identify additional evidence-based criteria.
      The project team evaluated all the requirements and indicators with consensus
      meeting methodology, then those applicable to the Italian context were grouped
      into a set of "focus areas". RESULTS: The analysis of international systems and
      Italian regional accreditation manuals led to the identification respectively of
      19 and 14 main requirements, with relevant heterogeneity in their application.
      Additional evidence-based criteria were included from the reviews analysis. From
      the consensus among the project team members all the standards were compared and
      20 different thematic areas were identified, with a total of 96 requirements and
      indicators for preventing and monitoring HAIs. CONCLUSIONS: The study reveals a
      great heterogeneity in the definition of accreditation criteria between the
      Italian regions. The introduction of a uniform, synthetic assessment instrument,
      based on the review of national and international standards, may serve as a self
      assessment tool to evaluate the achievement of a minimum standards set for HAIs
      prevention and control in healthcare facilities. This may be used as an
      assessment tool by the Italian institutional accreditation system, also useful to
      reduce regional disparities.

PMID- 29048454
TI  - Are the school prevention programmes - aimed at de-normalizing smoking among
      youths - beneficial in the long term? An example from the Smoke Free Class
      Competition in Italy.
AB  - Tobacco smoking by young people is of great concern because it usually leads to
      regular smoking, nicotine addiction and quitting difficulties. Young people
      "hooked" by tobacco maintain the profits of the tobacco industry by replacing
      smokers who quit or die. If new generations could be tobacco-free, as supported
      by tobacco endgame strategies, the tobacco epidemic could end within decades.
      Smoking prevention programmes for teens are offered by schools with the aim to
      prevent or delay smoking onset. Among these, the Smoke Free Class Competition
      (SFC) was widely implemented in Europe. Its effectiveness yielded conflicting
      results, but it was only evaluated at short/medium term (6 - 18 months). The aim
      of this study is to evaluate its effectiveness after a longer follow-up (3 to 5
      years) in order to allow enough time for the maturing of the students and the
      internalization of the experience and its contents. Fifteen classes were randomly
      sampled from two Italian high schools of Bologna province that regularly offered
      the SFC to first year students; 382 students (174 participating in the SFC and
      208 controls) were retrospectively followed-up and provided their "smoking
      histories". At the end of their last year of school (after 5 years from the SFC),
      the percentage of students who stated that they were regular smokers was lower
      among the SFC students than in controls: 13.5% vs 32.9% (p=0.03). From the
      students' "smoking histories", statistically significant protective ORs were
      observed for SFC students at the end of 1st and 5th year: 0.42 (95% CI 0.19-0.93)
      and 0.32 (95% CI 0.11-0.91) respectively. Absence of smokers in the family was
      also a strongly statistically significant factor associated with being a non
      smoker student. These results suggest that SFC may have a positive impact on
      lowering the prevalence of smoking in the long term (5 years).

PMID- 29048455
TI  - Improving knowledge and behaviors on diet and physical activity in children:
      results of a pilot randomized field trial.
AB  - BACKGROUND: The aim of this study was to increase the knowledge of healthy
      eating, to encourage change in nutritional behavior in accordance with the
      Mediterranean diet and to promote physical activity in children aged 7 to 9 years
      and their parents in a school setting through the use of cards and board games of
      the project Giochiamo (Let us play). METHODS: This experimental randomized field
      trial enrolled children in a school setting. The trial consisted of two phases.
      The first phase, including both intervention and control groups, encompassed a
      informative session about the food pyramid and physical activity (PA) by experts
      of public health and preventive medicine. The second phase, including only the
      experimental groups, involved games focusing on the main concepts of the food
      pyramid and PA. A questionnaire was administered before the intervention and
      after one month in order to assess changing in knowledge and behavior scores.
      RESULTS: Eighty-nine children were randomly allocated in the intervention (22
      children of the fourth year, 22 children of the second year) and the control
      group (23 children of the fourth year, 22 children of the second year). The
      univariate analyses showed significant differences (p = 0,004) between
      intervention and control groups for behavior score after the intervention. In
      particular, in a stratified analysis classes of the second year showed
      significant differences for knowledge score (p = 0,005) and for behavior score (p
      = 0,002), resulting higher among the intervention group. No significant
      differences resulted in classes of the fourth year for both scores. CONCLUSIONS:
      The results of the Giochiamo project clearly demonstrate that the lecture and the
      games were effective to improve knowledge and behavior habits on the
      Mediterranean diet and PA. Second year students showed significant differences
      for knowledge and behavior score in comparison to fourth year students suggesting
      that, the earlier the intervention occurs, the better are the results in terms of
      improvement of knowledge and eating habits and PA behaviors.

PMID- 29048456
TI  - An evaluation of attitude toward vaccines among healthcare workers of a
      University Hospital in Southern Italy.
AB  - BACKGROUND: Vaccination is an effective and safe health technology. Despite this
      vaccine coverage falls short of national and international targets. Study design.
      The aim of the study was to evaluate the views of medical staff at Messina
      University Hospital regarding vaccinations, their current and future vaccination
      status and whether they recommend it to their patients. METHODS: The study was
      conducted from April 2016 to March 2017 by an anonymous face-to-face
      questionnaire submitted to HCWs. RESULTS: A general lack of confidence and
      insecurity about vaccination was shown by a substantial proportion of physicians
      analyzed while pediatricians showed a positive attitude to vaccines. However,
      many physicians had not been immunized with the recommended vaccines for HCWs and
      therefore represent a potential source of infection for both patients and the
      general population. CONCLUSIONS: Despite the evidence of the effectiveness and
      safety of vaccines, compliance by HCWs remains very low for a variety of reasons.
      A range of measures are therefore needed to ensure their use, not only by the
      general population, but also by doctors who should be their major promoters.

PMID- 29048458
TI  - A probabilistic pathway score (PROPS) for classification with applications to
      inflammatory bowel disease.
AB  - Summary: Gene-based supervised machine learning classification models have been
      widely used to differentiate disease states, predict disease progression and
      determine effective treatment options. However, many of these classifiers are
      sensitive to noise and frequently do not replicate in external validation sets.
      For complex, heterogeneous diseases, these classifiers are further limited by
      being unable to capture varying combinations of genes that lead to the same
      phenotype. Pathway-based classification can overcome these challenges by using
      robust, aggregate features to represent biological mechanisms. In this work, we
      developed a novel pathway-based approach, PRObabilistic Pathway Score, which uses
      genes to calculate individualized pathway scores for classification. Unlike
      previous individualized pathway-based classification methods that use gene sets,
      we incorporate gene interactions using probabilistic graphical models to more
      accurately represent the underlying biology and achieve better performance. We
      apply our method to differentiate two similar complex diseases, ulcerative
      colitis (UC) and Crohn's disease (CD), which are the two main types of
      inflammatory bowel disease (IBD). Using five IBD datasets, we compare our method
      against four gene-based and four alternative pathway-based classifiers in
      distinguishing CD from UC. We demonstrate superior classification performance and
      provide biological insight into the top pathways separating CD from UC.
      Availability and Implementation: PROPS is available as a R package, which can be
      downloaded at http://simtk.org/home/props or on Bioconductor. Contact:
      rbaltman@stanford.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29048459
TI  - An Efficient, Large-Scale Survey of Hepatitis C Viremia in the Democratic
      Republic of the Congo Using Dried Blood Spots.
AB  - Background: Efficient viral load testing is needed for hepatitis C (HCV)
      surveillance and diagnosis. HCV viral load testing using dried blood spots
      (DBSs), made with a single drop of finger-prick whole blood on filter paper, is a
      promising alternative to traditional serum- or plasma-based approaches. Methods:
      We adapted the Abbott Molecular m2000 instrument for high-throughput HCV viremia
      testing using DBSs with simple specimen processing and applied these methods to
      estimate the national burden of infection in the Democratic Republic of the Congo
      (DRC). We tested DBSs collected during the 2013-2014 DRC Demographic and Health
      Survey, including 1309 adults >=40 years of age. HCV-positive samples underwent
      targeted sequencing, genotyping, and phylogenetic analyses. Results: This high
      throughput screening approach reliably identified HCV RNA extracted from DBSs
      prepared using whole blood, with a 95% limit of detection of 1196 (95% confidence
      interval [CI], 866-2280) IU/mL for individual 6-mm punches and 494 (95% CI, 372
      1228) IU/mL for larger 12-mm punches. Fifteen infections were identified among
      samples from the DRC Demographic and Health Survey; the weighted country-wide
      prevalence of HCV viremia was 0.9% (95% CI, 0.3%-1.6%) among adults >=40 years of
      age and 0.7% (95% CI, .6%-.8%) among human immunodeficiency virus-infected
      subjects. All successfully genotyped cases were due to genotype 4 infection.
      Conclusions: DBS-based HCV testing represents a useful tool for the diagnosis and
      surveillance of HCV viremia and can easily be incorporated into specimen referral
      systems. Among adults >=40 years of age in the DRC, 100000-200000 may have active
      infection and be eligible for treatment.

PMID- 29048460
TI  - Cardiovascular magnetic resonance imaging in patients with cardiac implantable
      electronic devices: a device-dependent imaging strategy for improved image
      quality.
AB  - Aims: To prospectively determine evaluability of routine cardiovascular magnetic
      resonance (CMR) diagnostic modules in a referral population of implanted rhythm
      device all-comers, and to establish a device-dependent CMR imaging strategy to
      achieve optimal image quality. Methods and results: One hundred and twenty-eight
      patients with cardiac implantable electronic devices [insertable cardiac
      monitoring system, n = 14; implantable loop-recorder, n = 21; pacemaker, n = 31;
      implantable cardioverter-defibrillator (ICD), n = 50; and cardiac
      resynchronization therapy defibrillator (CRT-D), n = 12] underwent clinically
      indicated CMR at 1.5 T. CMR protocols were tailored to the clinical indication
      and consisted of cine, perfusion, T1-/T2-weighted, late-gadolinium enhancement
      (LGE), 3D angiographic, and post-contrast cine spoiled gradient echo (SGE) scans.
      Image quality was determined using a 4-grade visual score per myocardial segment.
      Segmental evaluability was strongly influenced by device type and location with
      the highest proportion of non-diagnostic images encountered in the presence of
      ICD/CRT-D systems. Cine steady-state free-precession (SSFP) imaging was found to
      be mostly non-diagnostic in ICD/CRT-D patients, but a significant improvement of
      image quality was demonstrated when using SGE sequences with a further
      incremental improvement post-contrast resulting in an overall four-fold higher
      likelihood of achieving good image quality. LGE scans were found to be non
      diagnostic in about one-third of left-ventricular segments of ICD/CRT-D patients
      but were artefact-free in > 94% for all other device types. Conclusion: Device
      type and location constitute the main independent predictors of CMR image quality
      and thus, need to be considered during protocol adaptation. Most notably, post
      contrast SGE cine imaging proved superior to conventionally used SSFP sequences.
      Thus, following the proposed device-dependent CMR imaging strategy, diagnostic
      image quality can be achieved in the majority of device patients.

PMID- 29048461
TI  - SliceMap: an algorithm for automated brain region annotation.
AB  - Summary: Many neurodegenerative disorders, such as Alzheimer's Disease, pertain
      to or spread from specific sites of the brain. Hence, accurate disease staging or
      therapy assessment in transgenic model mice demands automated analysis of
      selected brain regions. To address this need, we have developed an algorithm,
      termed SliceMap, that enables contextual quantification by mapping anatomical
      information onto microtome-cut brain slices. For every newly acquired high
      resolution image of a brain slice, the algorithm performs a coarse congealing
      based registration to a library of pre-annotated reference slices. A subset of
      optimally matching reference slices is then used for refined, elastic
      registration. Morphotextural metrics are used to measure registration performance
      and to automatically detect poorly cut slices. We have implemented our method as
      a plugin for FIJI image analysis freeware, and we have used it to regionally
      quantify tau pathology in brain slices from a tauopathy (P301S) mouse model. By
      enabling region-based quantification, our method contributes to a more accurate
      assessment of neurodegenerative disease development. Availability and
      implementation: The method is available as a plugin for FIJI from
      https://github.com/mbarbie1/SliceMap/, along with an example dataset and user
      instructions. Contact: winnok.devos@uantwerpen.be. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29048462
TI  - Obesity-induced vascular dysfunction and arterial stiffening requires endothelial
      cell arginase 1.
AB  - Aims: Elevation of arginase activity has been linked to vascular dysfunction in
      diabetes and hypertension by a mechanism involving decreased nitric oxide (NO)
      bioavailability due to L-arginine depletion. Excessive arginase activity also can
      drive L-arginine metabolism towards the production of ornithine, polyamines, and
      proline, promoting proliferation of vascular smooth muscle cells and collagen
      formation, leading to perivascular fibrosis. We hypothesized that there is a
      specific involvement of arginase 1 expression within the vascular endothelial
      cells in this pathology. Methods and results: To test this proposition, we used
      models of type 2 diabetes and metabolic syndrome. Studies were performed using
      wild type (WT), endothelial-specific arginase 1 knockout (EC-A1-/-) and
      littermate controls(A1con) mice fed high fat-high sucrose (HFHS) or normal diet
      (ND) for 6 months and isolated vessels exposed to palmitate-high glucose (PA/HG)
      media. Some WT mice or isolated vessels were treated with an arginase inhibitor,
      ABH [2-(S)-amino-6-boronohexanoic acid. In WT mice, the HFHS diet promoted
      increases in body weight, fasting blood glucose, and post-prandial insulin levels
      along with arterial stiffening and fibrosis, elevated blood pressure, decreased
      plasma levels of L-arginine, and elevated L-ornithine. The HFHS diet or PA/HG
      treatment also induced increases in vascular arginase activity along with
      oxidative stress, reduced vascular NO levels, and impaired endothelial-dependent
      vasorelaxation. All of these effects except obesity and hypercholesterolemia were
      prevented or significantly reduced by endothelial-specific deletion of arginase 1
      or ABH treatment. Conclusion: Vascular dysfunctions in diet-induced obesity are
      prevented by deletion of arginase 1 in vascular endothelial cells or arginase
      inhibition. These findings indicate that upregulation of arginase 1
      expression/activity in vascular endothelial cells has an integral role in diet
      induced cardiovascular dysfunction and metabolic syndrome.

PMID- 29048464
TI  - Differences in postoperative changes in pulmonary functions following
      segmentectomy compared with lobectomy.
AB  - OBJECTIVES: To clarify differences in postoperative changes in systemic and
      regional pulmonary functions between segmentectomy and lobectomy in patients with
      lung cancer, we compared the 2 procedures using lung perfusion scintigraphy with
      a fusion image of single-photon emission computed tomography and computed
      tomography. METHODS: This study is a retrospective matched cohort study of
      consecutively acquired data. Pulmonary function tests and perfusion single-photon
      emission computed tomography/computed tomography were conducted before surgery
      and 6 months after surgery to measure changes in forced expiratory volume in 1 s
      of a whole lung, contralateral lung and a lobe. After exactly matching the site
      of the resected lobe between the 2 procedures, propensity scores for age, sex,
      smoking status and pulmonary function were used to match them. RESULTS: Of the
      184 patients treated with segmentectomy and the 208 patients treated with
      lobectomy between 2013 and 2016, 103 patients were selected from each group after
      the matching. Whole lung function was significantly more preserved after
      segmentectomy than after lobectomy (P < 0.001). Segmentectomy preserved the
      function of the operated lobe with 48 +/- 21% of the preoperative function. The
      function of the ipsilateral non-operated lobe increased after segmentectomy (P =
      0.003) but not after lobectomy (P = 0.97). Contralateral lung function increased
      after both procedures (P < 0.001). CONCLUSIONS: Our data suggest that
      segmentectomy preserved whole lung function better than lobectomy, because it not
      only preserved the lobe but also increased the function of the ipsilateral non
      operated lobe. Lobectomy did not result in an increase of ipsilateral non
      operated lobe function. Contralateral lung function increased after both
      procedures. The postoperative increase in regional functions could be the result
      of compensatory lung growth.

PMID- 29048465
TI  - betaAPP Processing Drives Gradual Tau Pathology in an Age-Dependent Amyloid Rat
      Model of Alzheimer's Disease.
AB  - The treatment of Alzheimer's disease (AD) remains challenging and requires a
      better in depth understanding of AD progression. Particularly, the link between
      amyloid protein precursor (APP) processing and Tau pathology development remains
      poorly understood. Growing evidences suggest that APP processing and amyloid-beta
      (Abeta) release are upstream of Tau pathology but the lack of animal models
      mimicking the slow progression of human AD raised questions around this
      mechanism. Here, we described that an AD-like betaAPP processing in adults wild
      type rats, yielding to human APP, betaCTF and Abeta levels similar to those
      observed in AD patients, is sufficient to trigger gradual Tauopathy. The Tau
      hyperphosphorylation begins several months before the formation of both amyloid
      plaques and tangle-like aggregates in aged rats and without associated
      inflammation. Based on a longitudinal characterization over 30 months, we showed
      that extrasynaptic and emotional impairments appear before long-term potentiation
      deficits and memory decline and so before Abeta and Tau aggregations. These
      compelling data allowed us to (1) experimentally confirm the causal relationship
      between betaAPP processing and Tau pathology in vivo and without Tau transgene
      overexpression, (2) support the amyloidogenic cascade and (3) propose a 4-step
      hypothesis of prodromal AD progression.

PMID- 29048463
TI  - Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a
      role for mast cells.
AB  - Aims: Chronic kidney disease (CKD) is a powerful independent risk factor for
      cardiovascular events, including vein graft failure. Because CKD impairs the
      clearance of small proteins, we tested the hypothesis that CKD exacerbates vein
      graft disease by elevating serum levels of critical cytokines that promote vein
      graft neointimal hyperplasia. Methods and results: We modelled CKD in C57BL/6
      mice with 5/6ths nephrectomy, which reduced glomerular filtration rate by 60%,
      and we modelled vein grafting with inferior-vena-cava-to-carotid interposition
      grafting. CKD increased vein graft neointimal hyperplasia four-fold, decreased
      vein graft re-endothelialization two-fold, and increased serum levels of
      interleukin-9 (IL-9) five-fold. By quantitative immunofluorescence and
      histochemical staining, vein grafts from CKD mice demonstrated a ~two-fold higher
      prevalence of mast cells, and a six-fold higher prevalence of activated mast
      cells. Concordantly, vein grafts from CKD mice showed higher levels of TNF and
      NFkappaB activation, as judged by phosphorylation of NFkappaB p65 on Ser536 and
      by expression of VCAM-1. Arteriovenous fistula veins from humans with CKD also
      showed up-regulation of mast cells and IL-9. Treating CKD mice with IL-9
      neutralizing IgG reduced vein graft neointimal area four-fold, increased vein
      graft re-endothelialization ~two-fold, and reduced vein graft total and activated
      mast cell levels two- and four-fold, respectively. Treating CKD mice with the
      mast cell stabilizer cromolyn reduced neointimal hyperplasia and increased re
      endothelialization in vein grafts. In vitro, IL-9 promoted endothelial cell
      apoptosis but had no effect on smooth muscle cell proliferation. Conclusion: CKD
      aggravates vein graft disease through mechanisms involving IL-9 and mast cell
      activation.

PMID- 29048466
TI  - PyBEL: a computational framework for Biological Expression Language.
AB  - Summary: Biological Expression Language (BEL) assembles knowledge networks from
      biological relations across multiple modes and scales. Here, we present PyBEL; a
      software package for parsing, validating, converting, storing, querying, and
      visualizing networks encoded in BEL. Availability and implementation: PyBEL is
      implemented in platform-independent, universal Python code. Its source is
      distributed under the Apache 2.0 License at https://github.com/pybel. Contact:
      charles.hoyt@scai.fraunhofer.de. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29048467
TI  - Identification of copy number variations and translocations in cancer cells from
      Hi-C data.
AB  - Motivation: Eukaryotic chromosomes adapt a complex and highly dynamic three
      dimensional (3D) structure, which profoundly affects different cellular functions
      and outcomes including changes in epigenetic landscape and in gene expression.
      Making the scenario even more complex, cancer cells harbor chromosomal
      abnormalities (e.g., copy number variations (CNVs) and translocations) altering
      their genomes both at the sequence level and at the level of 3D organization.
      High-throughput chromosome conformation capture techniques (e.g., Hi-C), which
      are originally developed for decoding the 3D structure of the chromatin, provide
      a great opportunity to simultaneously identify the locations of genomic
      rearrangements and to investigate the 3D genome organization in cancer cells.
      Even though Hi-C data has been used for validating known rearrangements,
      computational methods that can distinguish rearrangement signals from the
      inherent biases of Hi-C data and from the actual 3D conformation of chromatin,
      and can precisely detect rearrangement locations de novo have been missing.
      Results: In this work, we characterize how intra and inter-chromosomal Hi-C
      contacts are distributed for normal and rearranged chromosomes to devise a new
      set of algorithms (i) to identify genomic segments that correspond to CNV regions
      such as amplifications and deletions (HiCnv), (Nurtdinov et al.) to call inter
      chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments,
      and (iii) to simulate Hi-C data from genomes with desired rearrangements and
      abnormalities (AveSim) in order to select optimal parameters for and to benchmark
      the accuracy of our methods. Our results on 10 different cancer cell lines with
      Hi-C data show that we identify a total number of 105 amplifications and 45
      deletions together with 90 translocations, whereas we identify virtually no such
      events for two karyotypically normal cell lines. Our CNV predictions correlate
      very well with whole genome sequencing (WGS) data among chromosomes with CNV
      events for a breast cancer cell line (r=0.89) and capture most of the CNVs we
      simulate using Avesim. For HiCtrans predictions, we report evidence from the
      literature for 30 out of 90 translocations for eight of our cancer cell lines.
      Furthermore, we show that our tools identify and correctly classify relatively
      understudied rearrangements such as double minutes (DMs) and homogeneously
      staining regions (HSRs). Conclusions: Considering the inherent limitations of
      existing techniques for karyotyping (i.e., missing balanced rearrangements and
      those near repetitive regions), the accurate identification of CNVs and
      translocations in a cost-effective and high-throughput setting is still a
      challenge. Our results show that the set of tools we develop effectively utilize
      moderately sequenced Hi-C libraries (100-300 million reads) to identify known and
      de novo chromosomal rearrangements/abnormalities in well-established cancer cell
      lines. With the decrease in required number of cells and the increase in
      attainable resolution, we believe that our framework will pave the way towards
      comprehensive mapping of genomic rearrangements in primary cells from cancer
      patients using Hi-C. Availability: CNV calling: https://github.com/ay
      lab/HiCnvTranslocation calling: https://github.com/ay-lab/HiCtransHi-C
      simulation: https://github.com/ay-lab/AveSim.

PMID- 29048469
TI  - Resilience to stress and risk of gastrointestinal infections.
AB  - Background: Exposure to psychological stress can elicit a physiological response
      that may influence characteristics of the gastrointestinal mucosa, including
      increased intestinal permeability, in turn possibly increasing susceptibility to
      gastrointestinal infections. We investigated whether low stress resilience in
      adolescence is associated with an 'increased' risk of gastrointestinal infections
      in subsequent adulthood. Methods: Data were provided by Swedish registers for a
      cohort of 237 577 men who underwent military conscription assessment in late
      adolescence (1969-76). As part of the assessment procedure, certified
      psychologists evaluated stress resilience through semi-structured interviews. The
      cohort was followed from conscription assessment until 31 December 2009 (up to
      age 57 years). Cox regression assessed the association of stress resilience with
      gastrointestinal infections (n = 5532), with adjustment for family background
      measures in childhood and characteristics in adolescence. Peptic ulcer disease
      (PUD) in adulthood was modelled as a time-dependent covariate. Results: Compared
      with high stress resilience, lower stress resilience was associated with a
      'reduced' risk of gastrointestinal infections after adjustment for family
      background in childhood, characteristics in adolescence and PUD in adulthood,
      with hazard ratios (and 95% confidence intervals) of 0.88 (0.81-0.97) and 0.83
      (0.77-0.88) for low and moderate stress resilience, respectively. Conclusion:
      Lower stress resilience in adolescence is associated with reduced risk of
      gastrointestinal infections in adulthood, rather than the hypothesized increased
      risk.

PMID- 29048470
TI  - Physical activity to reduce mortality risk.

PMID- 29048468
TI  - Policy determinants of physical activity across the life course: a 'DEDIPAC'
      umbrella systematic literature review.
AB  - Background: Despite the large number of studies and reviews available, the
      evidence regarding the policy determinants of physical activity (PA) is
      inconclusive. This umbrella systematic literature review (SLR) summarizes the
      current evidence on the policy determinants of PA across the life course, by
      pooling the results of the available SLRs and meta-analyses (MAs). Methods: A
      systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus and
      SPORTDiscus databases up to April 2016. SLRs and MAs of observational studies
      investigating the association between policy determinants of PA and having PA as
      outcome were considered eligible. The extracted data were assessed based on the
      importance of the determinants, the strength of evidence and the methodological
      quality. Results: Fourteen reviews on 27 policy determinants of PA were eligible
      for this umbrella SLR. The majority of the reviews were of moderate quality.
      Among children, a clear association between time spent outdoors and PA emerged.
      Among adults, working hours were negatively associated with PA, though evidence
      was limited. At the population level, community- and street-scale urban design
      and land use policies were found to positively support PA levels, but levels of
      evidences were low. Conclusions: With this umbrella SLR the policy determinants
      of PA at individual-level and population-level have been summarized and assessed.
      None of the investigated policy determinants had a convincing level of evidence,
      and very few had a probable level of evidence. Further research is needed,
      preferably by using prospective study designs, standardized definitions of PA and
      objective measurement of PA.

PMID- 29048471
TI  - A new staging system for cardiac transthyretin amyloidosis.
AB  - Aims: Cardiac transthyretin (ATTR) amyloidosis is an increasingly recognized,
      progressive, and fatal cardiomyopathy, the natural history of which remains
      unclear. We sought to establish and validate a new prognostic staging system
      applicable to patients with both wild-type ATTR (ATTRwt) and hereditary variant
      ATTR (ATTRv) amyloid cardiomyopathy. Methods and results: Eight hundred and sixty
      nine patients with cardiac ATTR amyloidosis (553 with ATTRwt and 316 with ATTRv)
      attending the UK National Amyloidosis Centre were stratified into three disease
      stages at baseline on the basis of cut points in two universally measured
      biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated
      glomerular filtration rate (eGFR). Stage I was defined as NT-proBNP <=3000 ng/L
      and eGFR >=45 ml/min, Stage III was defined as NT-proBNP >3000 ng/L and eGFR <45
      ml/min, and the remainder were Stage II. The staging system was validated in a
      cohort of 318 patients with cardiac ATTR amyloidosis from France. Median survival
      among 393 (45%) Stage I patients was 69.2 months, 334 (38%) Stage II patients was
      46.7 months, and 142 (16%) Stage III patients was 24.1 months (P < 0.0001). After
      adjusting for age, compared with Stage I, the hazard ratio (HR) for death for
      Stage II was 2.05 [confidence interval (CI) 1.54-2.72, P < 0.001] and for Stage
      III was 3.80 (CI 2.73-5.28, P < 0.001). HRs and statistical significance were
      little altered by transthyretin genotype and were maintained in the validation
      cohort. Conclusion: This simple, universally applicable staging system stratifies
      patients with both ATTRwt and ATTRv amyloid cardiomyopathy into prognostic
      categories. It will be of value in the design of forthcoming clinical trials of
      novel amyloid-specific therapies.

PMID- 29048472
TI  - Trajectories of long-term care in 28 EU countries: evidence from a time series
      analysis.
AB  - Background: This study aims to confirm whether an increase in the number of
      elderly people and a worsening in the auto-evaluation of the general health state
      and in the limitation of daily activities result in increases in the offered
      services (beds in residential LTC facilities), in the social and healthcare
      expenditure and, consequently, in the percentage of LTC users. Methods: This
      study used a pooled, cross-sectional, time series design focusing on 28 European
      countries from 2004 to 2015. The indicators considered are: population aged 65
      years and older; self-perceived health (bad and very bad) and long-standing
      limitations in usual activities; social protection benefits (cash and kind); LTC
      beds in institutions; LTC recipients at home and in institutions; healthcare
      expenditures and were obtained from the Organization for Economic Co-operation
      and Development and Eurostat. Results: The proportion of elderly people
      increased, and conversely, the percentage of subjects who had a self-perceived
      bad or very bad health decreased. Moreover, there was an orientation to reduce
      the share of elderly people who received LTC services and to focus on the most
      serious cases. Finally, the combination of formal care at home and in
      institutions resulted in most Member States shifting from institutional care to
      home care services. Conclusions: Demographic, societal, health changes could
      considerably affect LTC needs and services, resulting in higher LTC related
      costs. Thus, knowledge of LTC expenditures and the demand for services could be
      useful for healthcare decision makers.

PMID- 29048473
TI  - Use of taurolidine in lung transplantation for cystic fibrosis and impact on
      bacterial colonization.
AB  - OBJECTIVES: The presence of bacterial colonization that causes chronic pulmonary
      infections in cystic fibrosis (CF) patients remains a key issue before lung
      transplantation. We sought to assess the impact of intraoperative taurolidine
      lavage on bacterial colonization and long-term outcomes following lung
      transplantation in CF patients. METHODS: Between 2007 and 2013, 114 CF patients
      underwent lung transplantation at our institute, and taurolidine 2% bronchial
      lavage was applied in a substantial proportion of patients (n = 42). A detailed
      analysis of donor and recipient bacterial colonization status in treatment and
      control groups and their impact on outcome was performed. RESULTS: The proportion
      of recipients colonized with Pseudomonas aeruginosa was lower in the taurolidine
      group at 3 months (P < 0.001) and at 1 year (P = 0.053) postoperatively, despite
      no differences before transplant (P = 1.000). Moreover, a complete eradication of
      Burkholderia cepacia and Stenotrophomonas maltophilias colonizations could be
      achieved in the taurolidine group, whereas in the non-taurolidine group,
      persistent B. cepacia and S. maltophilias colonizations were observed. Early
      outcome in the taurolidine group was superior regarding fraction of expired
      volume in 1 s at 3 and 6 months after surgery with 74.5 +/- 14.6 vs 60.4 +/- 17.5
      (P < 0.001) and 80.6 +/- 16.9 vs 67.2 +/- 19.4 (P = 0.005) percent of predicted
      values, respectively. In terms of long-term overall survival (P = 0.277) and
      freedom from bronchiolitis obliterans syndrome (P = 0.979), both groups were
      comparable. CONCLUSIONS: Taurolidine might be associated with a reduced
      proportion of CF patients colonized with multiresistant pathogens, particularly
      with P. aeruginosa. Long-term results should be further assessed in larger
      multicentre trials.

PMID- 29048474
TI  - Transinnominate approach for transcatheter aortic valve replacement: single
      centre experience of minimally invasive alternative access.
AB  - OBJECTIVES: Iliofemoral arteries have been the preferred access for transcatheter
      aortic valve replacement (TAVR). When these arteries are too small, calcified or
      tortuous, an alternative access must be considered. Transinnominate (TI) access
      is an extrathoracic approach that does not require manipulation of major
      neurovascular structures or the apex. The aim of this study is to evaluate the
      efficacy and safety of TI TAVR as an alternative access in patients with severe
      aortic stenosis not amenable to a transfemoral approach. METHODS: Thirteen
      patients with severe aortic stenosis underwent TI TAVR between February 2016 and
      January 2017 at our institution. The average Society of Thoracic Surgeons (STS)
      score was 7.7 +/- 4.5%. Eight patients had previous surgical revascularization, 7
      of which involved the left thoracic artery. All patients underwent preoperative
      computed tomography angiography that revealed significant atheromatous and
      calcific disease of the iliofemoral vessels and/or the descending aorta. The
      innominate artery was found to be of appropriate calibre (>10 mm), free of plaque
      and easy to access via surgical incision. Fusion multimodality imaging was
      utilized in all cases to guide the procedure. RESULTS: The innominate artery was
      accessed via a 2-inch right parasternal supraclavicular incision. Nine self
      expandable valves and 4 balloon-expandable valves were implanted. Procedural
      success occurred in all cases without intraprocedural and in-hospital mortality.
      No neurological deficits or vascular complications were recorded; postoperative
      bleeding was trivial. Ten patients were discharged on Day 3 and 3 patients who
      required PPM on Day 5. CONCLUSIONS: TI approach represents a safe, reproducible
      and minimally invasive hybrid technique for TAVR in high-risk patients. In our
      early experience, surgical trauma and perioperative complications are minimal
      with rapid patient recovery.

PMID- 29048475
TI  - In vitro infection with Mycobacterium tuberculosis induces a distinct
      immunological pattern in blood from healthy relatives of tuberculosis patients.
AB  - Part of the susceptibility to tuberculosis has a genetic basis, which is clear in
      primary immunodeficiencies, but is less evident in apparently immunocompetent
      subjects. Immune responses were analysed in blood samples from tuberculosis
      patients and their healthy first-degree relatives who were infected in vitro with
      mycobacteria (either Mycobacterium tuberculosis or M. bovis BCG). The
      antimicrobial activity against M. tuberculosis in blood from relatives was
      significantly lower than that observed in healthy controls. Tuberculosis patients
      exhibited a higher number of neutrophils, and monocyte phagocytosis was inhibited
      in both relatives and tuberculosis patients. A remarkable finding was that the
      production of reactive oxygen species by infected neutrophils was higher in
      relatives than in healthy controls. A higher production of TNFalpha in infected
      blood from relatives was also observed. These results may indicate that relatives
      display a stronger inflammatory response and that their immune response to M.
      tuberculosis is different from those of unrelated controls. First-degree
      relatives may represent a highly informative group for the analysis of
      tuberculosis susceptibility.

PMID- 29048476
TI  - Burnout in Nurses Working With Youth With Chronic Pain: A Mixed-Methods Analysis.
AB  - Objective: Nursing is a rewarding but also challenging profession. Nurses are at
      risk for burnout and premature exit from the profession, which is detrimental to
      them, their patients, and the healthcare system. There are few studies examining
      the unique correlates of burnout in nurses working with pediatric populations.
      The current 2-study project used mixed-methods (qualitative and then
      quantitative) analysis to explore burnout in nurses working in an inpatient unit
      with youth with chronic pain. Method: Study I participants included all of the 32
      nurses who worked in an inpatient pediatric unit, which admits patients with
      chronic pain. Qualitative analyses of focus groups were used to extract themes.
      These themes were examined via a quantitative battery completed by 41 nurses from
      2 inpatient pediatric units with youth with chronic pain. Results: The themes
      were burnout, moral distress, negative beliefs about chronic pain, barriers to
      pain management, fear of losing compassion, coworker support as a coping method,
      time worked in the unit, professional self-efficacy, and negative views of the
      hospital environment. Quantitative results supported most of the qualitative
      findings, and taken together, the findings supported a model of burnout in nurses
      working with youth with chronic pain. Conclusions: Conclusions We integrated
      qualitative and quantitative findings to develop a model of nurse burnout. This
      model provides a framework for evaluating and targeting burnout in nurses working
      with pediatric patients with chronic pain.

PMID- 29048478
TI  - The Role of Authoritative Parenting in Adolescent Type 1 Diabetes Management.
AB  - Objective: Adolescents with Type 1 diabetes are at risk for poorer adherence,
      lower quality of life (QOL), and poorer glycemic control (HbA1c). Authoritative
      parenting (AP) along with youth adherence and QOL was hypothesized to relate to
      better HbA1c. Methods: Parent-youth dyads (N = 257) completed baseline measures
      of adherence and QOL. Youth completed an AP questionnaire, and HbA1c samples were
      evaluated. Structural equation modeling determined relations among AP, adherence,
      QOL, and glycemic control. Results: AP indirectly linked to better HbA1c (beta = 
      .15, p = .021) through both better adherence and higher QOL. AP also was
      associated directly with better adherence (beta = .26, p = .001), which in turn
      was linked to better HbA1c (beta = -.35, p = .021). In addition, adherence was
      associated directly with QOL (beta = -.56, p = .001). Conclusions: Together,
      better youth adherence and higher QOL are two mechanisms by which more AP
      indirectly relates to better glycemic control during the early adolescent years.

PMID- 29048479
TI  - The Occurrence and Covariation of Binge Eating and Compensatory Behaviors Across
      Early to Mid-Adolescence.
AB  - The purpose of this study was to examine the occurrence and covariation of four
      eating disorder behaviors across the elementary, middle, and high school years.
      In a sample of 1,906 youth measured over 5 years at nine time points, from the
      past year of elementary school through the second year of high school, binge
      eating, purging (self-induced vomiting), compensatory exercise, and fasting
      behavior were assessed by self-report. Over the 5-year period, rates of binge
      eating and purging increased but rates of compensatory exercise and fasting
      decreased. Girls and boys did not differ in their rates of engagement in any of
      the behaviors. Within time, the behaviors covaried modestly. Health-care
      professionals are advised to assess each behavior individually, rather than base
      interventions on the presence or absence of a diagnosable eating disorder. Gender
      should not be a basis for assessing for the presence of any of these behaviors.

PMID- 29048481
TI  - Parental Bonding in Adolescents With and Without Chronic Pain.
AB  - Objective: Parental responses influence children's pain; however, the specific
      role of parental bonding in pediatric pain has not been examined. Depressive
      symptomology is frequently reported in children with chronic pain (CP) and may
      play a role in the relationship between parental bonding and pain. This study
      examined the connections between maternal/paternal bonding (perceived care and
      control) and symptoms of pain and depression in adolescents with CP and in
      healthy adolescents. Method: Participants included 116 adolescents (aged 12-17)
      with CP (n = 55) and without (n = 61). Adolescents completed the Parental Bonding
      Instrument separately for their mother and father, as well as measures of
      depression and pain. Results: Significant associations between parental bonding
      and adolescent pain and depression emerged in the pain group, but not in the
      healthy group. There were no differences in the impact of maternal versus
      paternal bonding on adolescent pain and depression. Mediation analyses revealed
      adolescent depression was a mediator of the relationship between maternal care
      and adolescent pain, and paternal control and adolescent pain in the group with
      CP. Conclusions: This study highlights the importance of considering parental
      bonding and adolescent depression in pediatric CP, suggesting that high paternal
      control and low maternal care contribute to increased pain in adolescents through
      heightened adolescent depressive symptoms. The findings emphasize the need for
      family-based treatment for CP that addresses parent behaviors and adolescent
      mental health.

PMID- 29048482
TI  - N-acetylglucosamine: more than a silent partner in insulin resistance.
AB  - Pedersen et al. (Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T,
      Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, et al. 2016.
      Human gut microbes impact host serum metabolome and insulin sensitivity. Nature.
      535: 376-381.) report that human serum levels of branched-chain amino acids
      (BCAA) and N-acetylglucosamine (GlcNAc) increase in proportion to insulin
      resistance. They focus on the microbiome and the contributing subset of microbe
      species, thereby demonstrating disease causality in mice. As either oral GlcNAc
      or BCAA in mice are known to increase insulin resistance and weight gain, we note
      that recently published molecular data argues for a cooperative interaction.

PMID- 29048480
TI  - Panax ginseng genome examination for ginsenoside biosynthesis.
AB  - Ginseng, which contains ginsenosides as bioactive compounds, has been regarded as
      an important traditional medicine for several millennia. However, the genetic
      background of ginseng remains poorly understood, partly because of the plant's
      large and complex genome composition. We report the entire genome sequence of
      Panax ginseng using next-generation sequencing. The 3.5-Gb nucleotide sequence
      contains more than 60% repeats and encodes 42 006 predicted genes. Twenty-two
      transcriptome datasets and mass spectrometry images of ginseng roots were adopted
      to precisely quantify the functional genes. Thirty-one genes were identified to
      be involved in the mevalonic acid pathway. Eight of these genes were annotated as
      3-hydroxy-3-methylglutaryl-CoA reductases, which displayed diverse structures and
      expression characteristics. A total of 225 UDP-glycosyltransferases (UGTs) were
      identified, and these UGTs accounted for one of the largest gene families of
      ginseng. Tandem repeats contributed to the duplication and divergence of UGTs.
      Molecular modeling of UGTs in the 71st, 74th, and 94th families revealed a
      regiospecific conserved motif located at the N-terminus. Molecular docking
      predicted that this motif captures ginsenoside precursors. The ginseng genome
      represents a valuable resource for understanding and improving the breeding,
      cultivation, and synthesis biology of this key herb.

PMID- 29048477
TI  - The role of toxins in Clostridium difficile infection.
AB  - Clostridium difficile is a bacterial pathogen that is the leading cause of
      nosocomial antibiotic-associated diarrhea and pseudomembranous colitis worldwide.
      The incidence, severity, mortality and healthcare costs associated with C.
      difficile infection (CDI) are rising, making C. difficile a major threat to
      public health. Traditional treatments for CDI involve use of antibiotics such as
      metronidazole and vancomycin, but disease recurrence occurs in about 30% of
      patients, highlighting the need for new therapies. The pathogenesis of C.
      difficile is primarily mediated by the actions of two large clostridial
      glucosylating toxins, toxin A (TcdA) and toxin B (TcdB). Some strains produce a
      third toxin, the binary toxin C. difficile transferase, which can also contribute
      to C. difficile virulence and disease. These toxins act on the colonic epithelium
      and immune cells and induce a complex cascade of cellular events that result in
      fluid secretion, inflammation and tissue damage, which are the hallmark features
      of the disease. In this review, we summarize our current understanding of the
      structure and mechanism of action of the C. difficile toxins and their role in
      disease.

PMID- 29048484
TI  - Adiponectin suppression of late inflammatory mediator, HMGB1-induced cytokine
      expression in RAW264 macrophage cells.
AB  - High-mobility group protein B1 (HMGB1) is a late inflammatory mediator released
      from inflammatory cells when stimulated, resulting in exaggerating septic
      symptoms. We recently demonstrated that full-length adiponectin, a potent anti
      inflammatory adipokine, inhibits lipopolysaccharide-induced HMGB1 release.
      However, the effects of adiponectin on HMGB1-induced exaggerating signals
      currently remain unknown. This study aimed to investigate the effects of
      adiponectin on the pro-inflammatory function of HMGB1 in RAW264 macrophage cells.
      The treatment of RAW264 cells with HMGB1 significantly up-regulated the mRNA
      expression of tumour necrosis factor-alpha, interleukin-1beta and C-X-C motif
      chemokine 10. HMGB1-induced cytokine expression was markedly suppressed by a toll
      like receptor 4 (TLR4) antagonist and slightly suppressed by an antagonist of the
      receptor for advanced glycation end products. A prior treatment with full-length
      or globular adiponectin dose-dependently suppressed all types of HMGB1-induced
      cytokine expression, and this suppression was abolished by compound C, an AMPK
      inhibitor, but not by the haem oxygenase (HO)-1 inhibitor, zinc protoporphyrin
      IX. Both forms of adiponectin also reduced the mRNA expression of TLR4. These
      results suggest that full-length and globular adiponectin suppress HMGB1-induced
      cytokine expression through an AMPK-mediated HO-1-independent pathway.

PMID- 29048483
TI  - Draft genome of the gayal, Bos frontalis.
AB  - Gayal (Bos frontalis), also known as mithan or mithun, is a large endangered semi
      domesticated bovine that has a limited geographical distribution in the hill
      forests of China, Northeast India, Bangladesh, Myanmar, and Bhutan. Many
      questions about the gayal such as its origin, population history, and genetic
      basis of local adaptation remain largely unresolved. De novo sequencing and
      assembly of the whole gayal genome provides an opportunity to address these
      issues. We report a high-depth sequencing, de novo assembly, and annotation of a
      female Chinese gayal genome. Based on the Illumina genomic sequencing platform,
      we have generated 350.38 Gb of raw data from 16 different insert-size libraries.
      A total of 276.86 Gb of clean data is retained after quality control. The
      assembled genome is about 2.85 Gb with scaffold and contig N50 sizes of 2.74 Mb
      and 14.41 kb, respectively. Repetitive elements account for 48.13% of the genome.
      Gene annotation has yielded 26 667 protein-coding genes, of which 97.18% have
      been functionally annotated. BUSCO assessment shows that our assembly captures
      93% (3183 of 4104) of the core eukaryotic genes and 83.1% of vertebrate universal
      single-copy orthologs. We provide the first comprehensive de novo genome of the
      gayal. This genetic resource is integral for investigating the origin of the
      gayal and performing comparative genomic studies to improve understanding of the
      speciation and divergence of bovine species. The assembled genome could be used
      as reference in future population genetic studies of gayal.

PMID- 29048485
TI  - Isavuconazole susceptibility of clinical Aspergillus fumigatus isolates and
      feasibility of isavuconazole dose escalation to treat isolates with elevated
      MICs.
AB  - Introduction: Isavuconazole is a new triazole approved for the treatment of
      invasive aspergillosis. We investigated isavuconazole MIC distributions,
      isavuconazole MIC correlations with those of other azoles and pharmacodynamics of
      isavuconazole in low-level resistant Aspergillus fumigatus isolates. Methods:
      Isavuconazole, voriconazole, itraconazole and posaconazole susceptibility of 487
      clinical A. fumigatus isolates was determined by EUCAST broth microdilution
      methodology. Using an in vivo estimation of the pharmacodynamic target and a
      previously published pharmacokinetic model, the probability of target attainment
      (PTA) was determined for a range of isavuconazole MICs using three dosing
      regimens (I, 200 mg once daily; II, 300 mg once daily; and III, 400 mg once
      daily). Results: Two hundred and seventy-nine of 487 isolates were phenotypically
      WT based on epidemiological cut-offs of voriconazole, itraconazole and
      posaconazole. Twenty-five of 279 phenotypically WT isolates and 196 of 208 non-WT
      isolates were classified as isavuconazole resistant based on the EUCAST
      breakpoint of 1 mg/L. Isavuconazole MICs showed very high correlation with
      voriconazole MICs, but moderate and low correlation with itraconazole and
      posaconazole MICs. The PTA for isolates with an isavuconazole MIC of 1 mg/L was
      92%-99% for 90% effective concentration (EC90) for the three dosing regimens. For
      isolates with an MIC of 2 mg/L the PTA decreased to 64%-92% for EC90.
      Conclusions: Our study indicated that isavuconazole and voriconazole MICs are
      highly correlated and that high-dose isavuconazole treatment might be an option
      in patients infected with an A. fumigatus isolate with an isavuconazole MIC of 2
      mg/L.

PMID- 29048486
TI  - Cancer progression models and fitness landscapes: a many-to-many relationship.
AB  - Motivation: The identification of constraints, due to gene interactions, in the
      order of accumulation of mutations during cancer progression can allow us to
      single out therapeutic targets. Cancer progression models (CPMs) use genotype
      frequency data from cross-sectional samples to identify these constraints, and
      return Directed Acyclic Graphs (DAGs) of restrictions where arrows indicate
      dependencies or constraints. On the other hand, fitness landscapes, which map
      genotypes to fitness, contain all possible paths of tumor progression. Thus, we
      expect a correspondence between DAGs from CPMs and the fitness landscapes where
      evolution happened. But many fitness landscapes-e.g. those with reciprocal sign
      epistasis-cannot be represented by CPMs. Results: Using simulated data under 500
      fitness landscapes, I show that CPMs' performance (prediction of genotypes that
      can exist) degrades with reciprocal sign epistasis. There is large variability in
      the DAGs inferred from each landscape, which is also affected by mutation rate,
      detection regime and fitness landscape features, in ways that depend on CPM
      method. Using three cancer datasets, I show that these problems strongly affect
      the analysis of empirical data: fitness landscapes that are widely different from
      each other produce data similar to the empirically observed ones and lead to DAGs
      that infer very different restrictions. Because reciprocal sign epistasis can be
      common in cancer, these results question the use and interpretation of CPMs.
      Availability and implementation: Code available from Supplementary Material.
      Contact: ramon.diaz@iib.uam.es. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29048487
TI  - The genome draft of coconut (Cocos nucifera).
AB  - Coconut palm (Cocos nucifera,2n = 32), a member of genus Cocos and family
      Arecaceae (Palmaceae), is an important tropical fruit and oil crop. Currently,
      coconut palm is cultivated in 93 countries, including Central and South America,
      East and West Africa, Southeast Asia and the Pacific Islands, with a total growth
      area of more than 12 million hectares [1]. Coconut palm is generally classified
      into 2 main categories: "Tall" (flowering 8-10 years after planting) and "Dwarf"
      (flowering 4-6 years after planting), based on morphological characteristics and
      breeding habits. This Palmae species has a long growth period before reproductive
      years, which hinders conventional breeding progress. In spite of initial
      successes, improvements made by conventional breeding have been very slow. In the
      present study, we obtained de novo sequences of the Cocos nucifera genome: a
      major genomic resource that could be used to facilitate molecular breeding in
      Cocos nucifera and accelerate the breeding process in this important crop. A
      total of 419.67 gigabases (Gb) of raw reads were generated by the Illumina HiSeq
      2000 platform using a series of paired-end and mate-pair libraries, covering the
      predicted Cocos nucifera genome length (2.42 Gb, variety "Hainan Tall") to an
      estimated *173.32 read depth. A total scaffold length of 2.20 Gb was generated
      (N50 = 418 Kb), representing 90.91% of the genome. The coconut genome was
      predicted to harbor 28 039 protein-coding genes, which is less than in Phoenix
      dactylifera (PDK30: 28 889), Phoenix dactylifera (DPV01: 41 660), and Elaeis
      guineensis (EG5: 34 802). BUSCO evaluation demonstrated that the obtained
      scaffold sequences covered 90.8% of the coconut genome and that the genome
      annotation was 74.1% complete. Genome annotation results revealed that 72.75% of
      the coconut genome consisted of transposable elements, of which long-terminal
      repeat retrotransposons elements (LTRs) accounted for the largest proportion
      (92.23%). Comparative analysis of the antiporter gene family and ion channel gene
      families between C. nucifera and Arabidopsis thaliana indicated that significant
      gene expansion may have occurred in the coconut involving Na+/H+ antiporter,
      carnitine/acylcarnitine translocase, potassium-dependent sodium-calcium
      exchanger, and potassium channel genes. Despite its agronomic importance, C.
      nucifera is still under-studied. In this report, we present a draft genome of C.
      nucifera and provide genomic information that will facilitate future functional
      genomics and molecular-assisted breeding in this crop species.

PMID- 29048489
TI  - Reliable GC Method for Related Substances in Divalproex Sodium Drug.
AB  - A specific GC method has been developed, optimized and validated for the
      determination of seven related substances namely N,N-dimethyl valpronamide,
      valeric acid, 2-methyl valeric acid, 2-ethyl valeric acid, 2-isopropyl valeric
      acid, 2-n-butyl valeric acid and 2-propyl-2-pentenoic acid in divalproex sodium
      (DPS) drug substance. Chromatographic separations of these seven impurities were
      achieved on DB-FFAP column (30 m * 0.53 mm, 1.0 MUm), which consists
      nitroterephthalic acid modified polyethylene glycol material as stationary phase.
      DPS is a coordination complex of the sodium valproate and valproic acid (VPA).
      Nonanoic acid is used as internal standard. All the seven related substances, VPA
      and nonanoic acid were extracted into dichloromethane and monitored by GC with
      flame ionization detector. The performance of the developed method was assessed
      by evaluating specificity, linearity, sensitivity, precision, accuracy and
      robustness. Forced degradation experiments were conducted to evaluate the
      degradation behavior of DPS. The established limits of detection (LODs) and
      limits of quantification (LOQs) values for the related substances were in the
      ranges of 4-5 and 12-15 MUg mL-1, respectively. Further, for VPA, LOD and LOQ
      values were 4 and 12 MUg mL-1, respectively. The correction factors of these
      related substances with respect to VPA and lie between 0.92 and 1.44. The average
      recoveries were in the range of 92.4-108.4%.

PMID- 29048488
TI  - Clinical and molecular features of MDR livestock-associated MRSA ST9 with
      staphylococcal cassette chromosome mecXII in humans.
AB  - Objectives: Clonal complex (CC) 9 is a prevalent livestock-associated (LA) MRSA
      clone in Asia whose pathogenicity in humans remains unknown. Methods: In 2012, we
      identified a patient with CC9-MRSA infection linked to livestock. After screening
      3328 clinical MRSA isolates from a national database, eight isolates (0.24%)
      collected between 1998 and 2012 were further confirmed to be of CC9. The detailed
      molecular features of the nine human CC9 strains and phylogenetic relatedness to
      animal CC9 strains were characterized with WGS. The antibiotic susceptibilities
      were determined and the clinical information was abstracted from medical records.
      Results: WGS grouped the CC9 strains into two clades, which were respectively
      associated with distinct toxome profiles, resistance gene profiles and
      staphylococcal cassette chromosomes (SCCmecXII for 7 isolates and SCCmecVT for 2
      isolates). The SCCmecXII strains were phylogenetically related to animal CC9-MRSA
      strains, negative for Panton-Valentine leucocidin and 100% resistant to
      ciprofloxacin, erythromycin, clindamycin, gentamicin and tigecycline. Four of the
      seven SCCmecXII isolates were associated with invasive diseases including
      bacteraemia leading to death (2) and osteomyelitis (2). Two SCCmecXII isolates
      were from patients with exposure to pigs before development of the MRSA diseases.
      Conclusions: The CC9-SCCmecXII MRSA prevailing in pigs in Asia is multidrug
      resistant and potentially pathogenic to humans. It is critical to continuously
      monitor the local epidemiology of MRSA and implement effective control measures
      to limit the spread of LA-MRSA between animals, to humans and in healthcare
      facilities.

PMID- 29048490
TI  - A Simple Method for the Simultaneous Determination of Pharmaceuticals and
      Personal Care Products in River Sediment by Ultrasound-Assisted Extraction
      Followed by Solid-Phase Microextraction Coupled with Gas Chromatography-Mass
      Spectrometry.
AB  - A simple method was developed using ultrasound-assisted extraction (UAE) combined
      with solid-phase microextraction (SPME) coupled with gas chromatography-mass
      spectrometry (GC-MS) for the simultaneous determination of eight different
      pharmaceuticals and personal care products (PPCPs) (ibuprofen, 2-benzyl-4
      chlorophenol, naproxen, triclosan, ketoprofen, diclofenac, bisphenol A and
      estrone) in river sediment. UAE conditions were optimized involving extraction
      variables such as extraction solvent, extraction time, sample amount, extraction
      temperature, pH and salt addition. A 100 mg of sediment was extracted by
      optimized UAE process using 7 mL deionized water (pH 3) + 1% methanol as solvent,
      room temperature and 1 min extraction at 70% of amplitude. A 5 mL of supernatant
      was subsequently extracted by SPME; the extracted analytes were derivatized on
      fiber in head-space mode with N-methyl-N-(tertbutyldimethylsilyl)
      trifluoroacetamide and then analyzed by GC-MS. The developed method was evaluated
      by testing: precision (CV < 8%), linearity (R  > 0.98), recoveries (56-108%),
      limits of detection (<0.25 ng/g) and quantitation (<0.8 ng/g). Finally, the
      method was successfully applied to sediment samples collected from Tula River,
      Hidalgo, Mexico (one of the most polluted river) in which naproxen and triclosan
      were identified at ng/g concentration levels. Quantitative results were compared
      with Tula River water samples, showing PPCPs distribution rate between water and
      sediment. The method is robust, simple and environmentally friendly, and provides
      straightforward analyses of these trace organic pollutants in sediment samples.

PMID- 29048491
TI  - Simultaneous Quantification of Eight Marker Compounds in Yongdamsagan-Tang Using
      a High-Performance Liquid Chromatography Equipped with Photodiode Array Detector.
AB  - Yongdamsagan-tang (YDSGT) has been used clinically for the treatment of acute-
      and chronic-urethritis, cystitis, orchitis and hypertension in Korea. In this
      study, a powerful method based on high-performance liquid chromatography (HPLC)
      with photodiode array (PDA) detection was established and validated for the
      quantitative analysis of eight components: chlorogenic acid, gentiopicroside,
      liquiritin apioside, liquiritin, nodakenin, baicalin, wogonoside and glycyrrhizin
      in YDSGT extract. The compounds were separated with a Gemini C18 analytical
      column (column temperature: 40 degrees C; mobile phase: 0.1% (v/v) aqueous
      trifluoroacetic acid (A) and acetonitrile (B); flow rate: 1.0 mL/min; injection
      volume: 10 MUL). The PDA detector scanned the range 190-800 nm and the marker
      compounds were monitored at 254, 275, 325 and 335 nm. The correlation
      coefficients of all compounds were 1.000 and the results showed excellent
      linearity. The lower limits of detection and quantification of the analytes were
      0.01-0.09 MUg/mL and 0.03-0.28 MUg/mL, respectively. The extraction recoveries of
      the marker compounds were 98.13-103.86%, with relative standard deviation values
      not exceeding 2.10%. The precision of intra- and inter-day measurements were 0.09
      1.78% and 0.12-2.09%, respectively. The content of the eight marker compounds in
      the freeze-dried YDSGT extract were 1.41-23.71 mg/g.

PMID- 29048492
TI  - Stability-Indicating UPLC and TLC-Densitometric Methods for Determination of
      Benztropine Mesylate and Its Carcinogenic Degradation Product.
AB  - Two accurate, precise and highly selective stability-indicating methods were
      adopted for simultaneous determination of benztropine mesylate (BNZ) in presence
      of its hepatotoxic and carcinogenic degradation product, benzophenone (BPH)
      either in pure form or in the pharmaceutical formulation without any preliminary
      separation steps. The first method is a thin layer chromatography (TLC)
      densitometric method that depended on separation of BNZ from its degradate on TLC
      aluminum plates precoated with silica gel 60 F254 as the stationary phase using a
      developing system consisted of hexane:methylene chloride:triethylamine (5:5:0.6,
      by volume) and scanning the separated bands at 235 nm. Linear regression analysis
      data for the calibration plots of BNZ and BPH showed perfect linear relationships
      over the concentration range of 1.5-10 and 1-10 MUg band-1, respectively. The
      second method is (UPLC) method, at which the mixture was separated on a reversed
      phase C8 analytical column (1.9 MUm ps, 50 mm * 2.1 i.d.) using a mobile phase of
      acetonitrile: aqueous sodium dodecyl sulfate (50:50, v/v) Adjusted to pH = 3 with
      phosphoric acid, at a flow rate of 0.5 mL min-1. Quantification was achieved at
      210 nm based on peak area and linear calibration curves over the concentration
      ranges of (20-200 MUg mL-1) and (5-50 MUg mL-1) for BNZ and BPH, respectively,
      were obtained. The investigated methods were successfully applied to available
      dosage form and method validation has been carried out. The results obtained by
      applying the proposed methods were statistically analyzed and compared with those
      obtained by reported one and no significant differences were obtained regarding
      both accuracy and precision.

PMID- 29048497
TI  - Unusual atrial myxoma with neovascularization associated with fistula to right
      atrium.

PMID- 29048496
TI  - Short-run and long-run effects of unemployment on suicides: does welfare regime
      matter?
AB  - Background: Disentangling the immediate effects of an unemployment shock from the
      long-run relationship has a strong theoretical rationale. Different economic and
      psychological forces are at play in the first moment and after prolonged
      unemployment. This study suggests a diverse impact of short- and long-run
      unemployment on suicides in liberal and social-democratic countries. Methods: We
      take a macro-level perspective and simultaneously estimate the short- and long
      run relationships between unemployment and suicide, along with the speed of
      convergence towards the long-run relationship after a shock, in a panel of 10
      high-income countries. We also account for unemployment benefit spending, the
      share of the population aged 15-34, and the crisis effects. Results: In the
      liberal group of countries, only a long-run impact of unemployment on suicides is
      found to be significant (P = 0.010). In social-democratic countries, suicides are
      associated with initial changes in unemployment (P = 0.028), but the positive
      link fades over time and becomes insignificant in the long run. Further, crisis
      effects are a much stronger determinant of suicides in social-democratic
      countries. Once the broad welfare regime is controlled for, changes in
      unemployment-related spending do not matter for preventing suicides. Conclusions:
      A generous welfare system seems efficient at preventing unemployment-related
      suicides in the long run, but societies in social-democratic countries might be
      less psychologically immune to sudden negative changes in their professional
      lives compared with people in liberal countries. Accounting for the different
      short- and long-run effects could thus improve our understanding of the
      unemployment-suicide link.

PMID- 29048495
TI  - Evidence of Disturbed Sleep in Children With Eosinophilic Esophagitis and
      Persistent Epigastric Pain.
AB  - Objective: To determine whether the experience of persistent epigastric pain is
      associated with sleep disturbances in children with eosinophilic esophagitis
      (EoE). We hypothesized that children with EoE and persistent epigastric pain
      would (1) self-report greater current and worst pain severity, and (2) experience
      more disturbed sleep on objective and subjective measures in comparison with
      children with EoE but no persistent pain and healthy children. Methods: Fifty
      children with EoE were recruited for this cross-sectional study, of which 24
      (48%) reported experiencing persistent epigastric pain. The remaining 26 (52%)
      children with EoE denied experiencing persistent pain. An additional 25 healthy
      children without EoE or persistent pain were included. All children provided
      severity ratings of current pain and worst pain experienced over the past week.
      Children then completed 12 consecutive nights of ambulatory sleep monitoring via
      actigraphy in the home. Caregivers provided information regarding their child's
      sleep patterns and internalizing symptoms. Results: Children with EoE and
      persistent pain reported significantly greater severity of current pain (p <
      .001) and worst pain over the past week (p < .001) compared with EoE without
      persistent pain and healthy children. Compared with the other groups, children
      with EoE and persistent pain also demonstrated greater actigraphic sleep
      disturbances, lower sleep efficiency (p = .004) and greater wake after sleep
      onset (p = .034). Conclusions: This study provides novel evidence that a
      significant proportion of children with EoE experience persistent symptoms of
      epigastric pain. Persistent pain was associated with significant sleep
      disturbances in children with EoE.

PMID- 29048498
TI  - The NHLI at Imperial College, London.

PMID- 29048499
TI  - Sylvia Priori, Researcher and Cardiologist.

PMID- 29048500
TI  - Silvia Priori MD PhD.

PMID- 29048501
TI  - The 'Divine' or 'Golden' Arterial Pulse.

PMID- 29048502
TI  - Daniel R Wagner: An appreciation.

PMID- 29048503
TI  - Stem cell therapy: from translational hurdles to new frontiers.

PMID- 29048504
TI  - Commentary: Understanding Stereoelectroencephalography: What's Next?

PMID- 29048506
TI  - The Comfort Ability Pain Management Workshop: A Preliminary, Nonrandomized
      Investigation of a Brief, Cognitive, Biobehavioral, and Parent Training
      Intervention for Pediatric Chronic Pain.
AB  - Objective: Psychological intervention is widely recognized as an integral part of
      the recovery process from pediatric chronic pain, but service acquisition is
      often limited by resource barriers. The aim of this study was to assess the
      feasibility, acceptability, and satisfaction of a brief, structured, skills
      based, group intervention designed expressly to address gaps in service delivery.
      Exploratory outcomes were also assessed. Method: Adolescents with chronic pain (n
      = 102; ages 10-17 years) and their mothers (n = 105) completed self-report
      questionnaires at baseline, 1-week, 1-month, and 3-month posttreatment. Results:
      This study demonstrated feasibility, and overall high acceptability and
      satisfaction among adolescents and parents. Exploratory analyses within this
      nonrandomized design suggest that adolescents demonstrate improvement in
      functionality (p = .0012), depression symptoms (p < .0001), and pain
      catastrophizing (p < .0001) by 1-month posttreatment and continued making gains
      over time. Parents made significant changes in parenting practices (p-values <
      .01) and in their beliefs about their adolescent's ability to manage pain (p <
      .001) by 1-week posttreatment and continued making gains over time. Conclusions:
      This brief intervention is both feasible and acceptable. Although small effect
      sizes were found for all outcome measures, parents and adolescents made
      significant gains postintervention. In the absence of a direct comparison group,
      we cannot determine if these improvements are exclusively attributable to the
      intervention. Future research will be needed to understand the degree to which
      this brief intervention may effectively enhance the attainment of evidence-based
      psychoeducation and cognitive behavioral skills that are known to foster adaptive
      parent and adolescent responses to chronic pain.

PMID- 29048507
TI  - The Future of the Discipline of Infectious Diseases.

PMID- 29048505
TI  - Outcome of patients with intracranial non-germinomatous germ cell tumors-lessons
      from the SIOP-CNS-GCT-96 trial.
AB  - Background: Following promising results to increase survival and reduce treatment
      burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted
      a European study using dose-intense chemotherapy followed by risk-adapted
      radiotherapy. Methods: All patients received 4 courses of
      cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal
      radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal
      radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites.
      Results: Patients with localized malignant NGGCT (n = 116) demonstrated 5-year
      progression-free survival (PFS) and overall survival (OS) of 0.72 +/- 0.04 and
      0.82 +/- 0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar,
      5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3
      patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen
      were local, 6 combined, and 7 distant relapses (outside radiation field).
      Seventeen of the 27 relapsed patients died of disease. Patients with metastatic
      disease (n = 33) demonstrated 5-year PFS and OS of 0.68 +/- 0.09 and 0.75 +/-
      0.08, respectively; 1 patient died following progression on treatment and 9 (27%)
      relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient
      with recurrence was salvaged. Multivariate analysis identified diagnostic alpha
      fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/mL, 19/149
      patients, of whom 11 relapsed; P < 0.0003) and residual disease following
      treatment, including after second-look surgery (n = 52/145 evaluable patients, 26
      relapsed; P = 0.0002) as significant prognostic indicators in this cohort.
      Conclusion: In localized malignant NGGCT, craniospinal radiotherapy could be
      avoided without increased relapses outside the radiotherapy field. Chemotherapy
      and craniospinal radiotherapy remain the gold standard for metastatic disease.

PMID- 29048508
TI  - Characterizing Human Immunodeficiency Virus Antiretroviral Therapy Interruption
      and Resulting Disease Progression Using Population-Level Data in British
      Columbia, 1996-2015.
AB  - Background: Suboptimal retention is among the biggest challenges to realize the
      full benefits of combination antiretroviral therapy (ART). We aimed to describe
      ART interruption patterns and identify determinants of disease progression while
      off ART in British Columbia, Canada. Methods: With population-level data on ART
      utilization and laboratory testing in British Columbia (1996-2015), we described
      the timing, frequency, and duration of ART interruptions (a gap of >=90 days in
      ART dispensation records). A 4-state continuous-time Markov model was implemented
      to identify determinants of disease progression during individuals' first ART
      interruption episode. Disease progression was measured according to CD4-based
      state transitions (cells/MUL: >=500 to 200-499; 200-499 to <200; >=500 to death;
      200-499 to death; and <200 to death). Results: Among individuals initiating ART,
      3129 (38.6%) interrupted ART over a median 8-year follow-up (interquartile range
      [IQR], 4.3-13.5 years). Those interrupting ART had a median of 1 interruption
      (IQR, 1.0-3.0), with the first interruption occurring 12.8 (IQR, 4.0-36.1) months
      after ART initiation, lasting for 7.5 (IQR, 4.1-20.3) months. The proportion of
      individuals interrupting ART within the first year of ART initiation decreased
      over time; however, the absolute number of individuals interrupting ART remained
      high. In a multivariable analysis, age, historical plasma viral load, and ART
      regimen changes prior to interruption were associated with increased hazard of
      CD4 decline and death. Conclusions: Our results demonstrate that ART
      interruptions are common even in a high-resource setting with universal free
      access to human immunodeficiency virus care. Further efforts are needed to
      promote ART reengagement and may consider prioritizing individuals with poorer
      prognostic factors.

PMID- 29048509
TI  - Plasma But Not Cerebrospinal Fluid Interleukin 7 and Interleukin 5 Levels Pre
      Antiretroviral Therapy Commencement Predict Cryptococcosis-Associated Immune
      Reconstitution Inflammatory Syndrome.
AB  - Background: Patients with human immunodeficiency virus/AIDS-associated
      cryptococcal meningitis (CM) frequently experience clinical deterioration, known
      as cryptococcosis-associated immune reconstitution inflammatory syndrome (C
      IRIS), upon initiation of antiretroviral therapy (ART). The immunological
      mechanisms underlying C-IRIS are incompletely defined and no reliable predictive
      biomarkers exist. We investigated whether plasma or cerebrospinal fluid (CSF)
      levels of cytokines and chemokines predicted C-IRIS and are potential predictive
      biomarkers. Methods: Patients with CM who experienced C-IRIS (N = 27) upon ART
      initiation were compared to CD4+ T-cell count-matched patients without C-IRIS (N
      = 27). Plasma and CSF collected pre-ART were assayed for cytokines and chemokines
      using a 17-plex Luminex kit or enzyme-linked immunosorbent assay. Cox
      proportional hazards regression and principal component analyses were also
      performed. Results: Plasma interleukin (IL) 2, IL-4, IL-5, IL-7, IL-17,
      interferon-gamma, and tumor necrosis factor-alpha levels were higher in C-IRIS
      patients compared to controls (all P < .05), with IL-5 and IL-7 significant after
      Bonferroni-Holm correction. In multivariate Cox proportional hazards regression,
      high IL-5 (hazard ratio [HR], 5.76 [95% confidence interval {CI}, .77-43.0]; P =
      .088) and IL-7 (HR, 9.30 [95% CI, 1.96-44.0]; P = .005) were predictive of C
      IRIS. Plasma IL-5 (P = .0008) and IL-10 (P = .0089) were lower in those who
      achieved CSF cryptococcal culture negativity compared to those with positive
      cultures pre-ART. There were no significant differences in CSF cytokine or
      chemokine levels between cases and controls. Conclusions: High plasma IL-5 and IL
      7 levels pre-ART were associated with increased risk of developing C-IRIS. High
      IL-5 levels may reflect a Th2 environment associated with impaired clearance of
      cryptococci while high IL-7 levels may reflect IL-7/IL-7R pathway dysfunction in
      T cells, both of which could be associated with C-IRIS immunopathogenesis.

PMID- 29048510
TI  - Donor-Derived Mycoplasma hominis and an Apparent Cluster of M. hominis Cases in
      Solid Organ Transplant Recipients.
AB  - Background: Invasive and disseminated Mycoplasma hominis infections are well
      recognized but uncommon complications in solid organ transplant recipients. In a
      single center, a cluster of M. hominis infections were identified in lung
      transplant recipients from the same thoracic intensive care unit (ICU). We sought
      to determine the source(s) of these infections. Methods: Medical records of the
      donor and infected transplant recipients were reviewed for clinical
      characteristics. Clinical specimens underwent routine processing with subculture
      on Mycoplasma-specific Hayflick agar. Mycoplasma hominis identification was
      confirmed using sequencing of the 16S ribosomal RNA gene. Mycoplasma hominis
      isolates were subjected to whole-genome sequencing on the Illumina NextSeq
      platform. Results: Three lung transplant recipients presented with invasive M.
      hominis infections at multiple sites characterized by purulent infections without
      organisms detected by Gram staining. Each patient had a separate donor; however,
      pretransplant bronchoalveolar lavage fluid was only available from the donor for
      patient 1, which subsequently grew M. hominis. Phylo- and pangenomic analyses
      indicated that the isolates from the donor and the corresponding recipient
      (patient 1) were closely related and formed a distinct single clade. In contrast,
      isolates from patients 2 and 3 were unrelated and divergent from one another.
      Conclusions: Mycoplasma hominis should be considered a cause of donor-derived
      infection. Genomic data suggest donor-to-recipient transmission of M. hominis.
      Additional patients co-located in the ICU were found to have genetically
      unrelated M. hominis isolates, excluding patient-to-patient transmission.

PMID- 29048511
TI  - Impact of Implementing National Guidelines on Antibiotic Prescriptions for Acute
      Respiratory Tract Infections in Pediatric Emergency Departments: An Interrupted
      Time Series Analysis.
AB  - Background: Many antibiotics are prescribed inappropriately in pediatric
      emergency departments (PEDs), but little data are available in these settings
      about effective interventions based on guidelines that follow the antimicrobial
      stewardship principle. Our aim was to assess the impact of implementing the 2011
      national guidelines on antibiotic prescriptions for acute respiratory tract
      infection (ARTI) in PEDs. Method: We conducted a multicentric, quasiexperimental,
      interrupted time series analysis of prospectively collected electronic data from
      7 French PEDs. We included all pediatric patients who visited a participating PED
      during the study period from November 2009 to October 2014 and were diagnosed
      with an ARTI. The intervention consisted of local protocol implementation,
      education sessions, and feedback. The main outcome was the antibiotic
      prescription rate of discharge prescriptions for ARTI per 1000 PED visits before
      and after implementation, analyzed using the segmented regression model. Results:
      We included 242534 patients with an ARTI. The intervention was associated with a
      significant change in slope for the antibiotic prescription rate per 1000 PED
      visits (-0.4% per 15-day period, P = .04), and the cumulative effect at the end
      of the study was estimated to be -30.9%, (95% CI [-45.2 to -20.1]), representing
      13136 avoided antibiotic prescriptions. The broad-spectrum antibiotic
      prescription relative percentage decreased dramatically (-62.7%, 95% CI [-92.8; 
      32.7]) and was replaced by amoxicillin. Conclusion: Implementation of the 2011
      national French guidelines led to a significant decrease in the antibiotic
      prescription rate for ARTI and a dramatic drop in broad-spectrum antibiotic
      prescriptions, in favor of amoxicillin.

PMID- 29048513
TI  - Sepsis National Hospital Inpatient Quality Measure (SEP-1): Multistakeholder Work
      Group Recommendations for Appropriate Antibiotics for the Treatment of Sepsis.
AB  - The Center for Medicare and Medicaid Services adopted the Early Management
      Bundle, Severe Sepsis/Septic Shock (SEP-1) performance measure to the Hospital
      Inpatient Quality Reporting Program in July 2015 to help address the high
      mortality and high cost associated with sepsis. The SEP-1 performance measure
      requires, among other critical interventions, timely administration of
      antibiotics to patients with sepsis or septic shock. The multistakeholder
      workgroup recognizes the need for SEP-1 but strongly believes that multiple
      antibiotics listed in the antibiotic tables for SEP-1 are not appropriate and the
      use of these antibiotics, as called for in the SEP-1 measure, is not in alignment
      with prudent antimicrobial stewardship. To promote the appropriate use of
      antimicrobials and combat antimicrobial resistance, the workgroup provides
      recommendations for appropriate antibiotics for the treatment of sepsis.

PMID- 29048512
TI  - Excellent Treatment Outcomes in Children Treated for Tuberculosis Under Routine
      Operational Conditions in Cape Town, South Africa.
AB  - Background: Tuberculosis (TB) remains a leading cause of death in children
      globally. It is recognized that human immunodeficiency virus (HIV) infection
      increases the risk of developing TB, but our understanding of the impact of HIV
      on risk of mortality for children treated for TB is limited. We aimed to identify
      predictors of mortality in children treated for drug-susceptible TB. Methods: A
      retrospective analysis of all children (<15 years of age) routinely treated
      between 2005 and 2012 for drug-susceptible TB in Cape Town was conducted using
      the programmatic electronic TB treatment database. Survival analysis using Cox
      regression was used to estimate hazard ratios for death. Logistic regression was
      used to estimate the odds of unfavorable outcomes. Results: Of 29519 children
      treated for and notified with TB over the study period, <1% died during TB
      treatment and 89.5% were cured or completed treatment. The proportion of children
      with known HIV status increased from 13% in 2005 to 95% in 2012. Children aged <2
      years had an increased hazard of death (adjusted hazard ratio [aHR], 3.13; 95%
      confidence interval [CI], 1.78-5.52) and greater odds of unfavorable outcome
      (adjusted odds ratio [aOR], 1.44; 95% CI, 1.24-1.66) compared with children aged
      10-14 years. HIV-infected children had increased mortality compared to HIV
      negative children (aHR, 6.85; 95% CI, 4.60-10.19) and increased odds of
      unfavorable outcome (aOR, 2.01; 95% CI, 1.81-2.23). Later year of TB treatment
      was a protective predictor for both mortality and unfavorable outcome.
      Conclusions: We demonstrate a dramatic improvement in HIV testing in children
      with TB over time and excellent overall treatment outcomes. HIV infection and
      young age were associated with increased risk of death and unfavorable outcome.

PMID- 29048514
TI  - Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic
      Area, 1995-2014: A Retrospective Cohort Study in Denmark.
AB  - Background: Despite a well-described symptomatology, treatment delay and sequelae
      are common in patients with Lyme neuroborreliosis (LNB). The aim of this study
      was to contribute to the knowledge about the symptomatology and epidemiology of
      LNB. Methods: We conducted a retrospective study of all LNB cases verified by a
      positive Borrelia intrathecal antibody index test performed at the Department of
      Microbiology, Odense University Hospital, Denmark, from 1995 through 2014.
      Results: The study included 431 patients; 126 were children. The mean incidence
      was 4.7 per 100 000 inhabitants per year. The median delay from neurological
      symptom debut to first hospital contact was 20 days and significantly longer for
      patients with symptom debut in the winter/early spring. The most common clinical
      symptoms were painful radiculitis (65.9%), cranial nerve palsy (43.4%), and
      headache (28.3%). A total of 30.6% were seen in >1 hospital department, and 85.6%
      were admitted during their course of treatment. Serum Borrelia immunoglobulin M
      and immunoglobulin G at the time of positive Borrelia intrathecal antibody index
      test were negative in 67 patients (15.5%). We found a median treatment delay of
      24 days, with no improvement in our 20-year study period. Residual symptoms
      following treatment were found in 28.1% of patients, and risk of residual
      symptoms was significantly associated with delay from symptom debut to initiation
      of treatment. Conclusions: The association between treatment delay and residual
      symptoms and the lack of improvement in treatment delay during the study period
      highlight the need for standardized diagnostic routines and a better follow-up
      for LNB patients. Our findings disprove that all patients with LNB develop
      positive serum Borrelia antibodies within 6 weeks after infection.

PMID- 29048517
TI  - Vertebral Compression Fracture After Spine Stereotactic Body Radiation Therapy: A
      Review of the Pathophysiology and Risk Factors.
AB  - BACKGROUND: Vertebral compression fracture (VCF) is a challenging and not
      infrequent complication observed following spine stereotactic body radiation
      therapy (SBRT). OBJECTIVE: To summarize the data from the multiple studies that
      have been published, addressing the risk and predictive factors for VCF post
      SBRT. METHODS: A systematic literature review was conducted. Studies were
      selected if they specifically addressed risk factors for post-SBRT VCF in their
      analyses. RESULTS: A total of 11 studies were identified, reporting both the risk
      of VCF post-SBRT and an analysis of risk factors based on univariate and
      multivariate analysis. A total of 2911 spinal segments were treated with a crude
      VCF rate of 13.9%. The most frequently identified risk factors on multivariate
      analysis were: lytic disease (hazard ratio [HR] range, 2.76-12.2), baseline VCF
      prior to SBRT (HR range, 1.69-9.25), higher dose per fraction SBRT (HR range,
      5.03-6.82), spinal deformity (HR range, 2.99-11.1), older age (HR range, 2.15
      5.67), and more than 40% to 50% of vertebral body involved by tumor (HR range,
      3.9-4.46). In the 9 studies that specifically reported on the use of post-SBRT
      surgical procedures, 37% of VCF had undergone an intervention (range, 11%-60%).
      CONCLUSION: VCF is an important adverse effect following SBRT. Risk factors have
      been identified to guide the selection of high-risk patients. Evidence-based
      algorithms with respect to patient selection and intervention are needed.

PMID- 29048518
TI  - Disease-Related Predictors of Health-Related Quality of Life in Youth With
      Eosinophilic Esophagitis.
AB  - Objective: To evaluate relations between health-related quality of life (HRQoL)
      and clinical symptom presentation in youth with eosinophilic esophagitis (EoE).
      We hypothesized that presence of dysphagia, reflux, nausea/vomiting, and
      epigastric pain would be related to poorer HRQoL. In predictive models, it was
      hypothesized that dysphagia, reflux, nausea/vomiting, and epigastric pain would
      each significantly and uniquely predict poorer HRQoL. Methods: This cross
      sectional, two-study design included 91 dyads comprised children with EoE and
      their respective caregivers across two tertiary children's hospitals, Site 1 in
      the Midwest (N = 47) and Site 2 in the Deep South (N = 44). Youth and their
      caregivers both completed questionnaires addressing HRQoL and EoE symptoms during
      clinic visits. Results: Per youth self-report, epigastric pain was found to be a
      significant predictor of poor physical and psychosocial HRQoL. Per caregiver
      proxy reports, epigastric pain was found to be a significant predictor of poor
      physical HRQoL. Conclusions: The clinical symptoms of EoE, specifically
      epigastric pain, were found to be predictive of the youth's HRQoL. Targeted
      interventions to help youth with EoE better manage their specific symptom
      experiences could ultimately improve HRQoL.

PMID- 29048519
TI  - Finding Silver Linings: A Preliminary Examination of Benefit Finding in Youth
      With Chronic Pain.
AB  - Background: Chronic pain is a pervasive condition in adolescence and is
      associated with significant psychological distress, functional disability, social
      isolation, and decreased quality of life for a subset of affected youth. There is
      a paucity of research examining potential resilience factors and adaptive
      processes in pediatric chronic pain. Benefit finding refers to the process of
      perceiving positive consequences in the face of adversity. Previous research on
      benefit finding in pediatric samples (e.g., oncology; acute injury) has yielded
      inconsistent results. This is the first study to examine this construct in youth
      with chronic pain. Objective: The objective of the current investigation was to
      extend previous research on benefit finding to adolescents with chronic pain and
      to assess relationships between benefit finding, internalizing mental health
      symptoms (i.e., anxiety, depression, and posttraumatic stress disorder [PTSD]),
      pain outcomes (pain intensity and interference), and quality of life. Methods:
      Psychometrically sound self-report measures of benefit finding, anxiety,
      depressive, and PTSD symptoms, pain intensity, pain interference, and quality of
      life were completed by 145 youth (67.4% female, Mage = 13.3 years, SD = 2.6),
      referred to a tertiary-level chronic pain program. Results: Benefit finding was
      significantly correlated with internalizing mental health symptoms, pain
      outcomes, and quality of life. Further, benefit finding significantly predicted
      children's self-reported pain intensity, pain interference, and quality of life
      when controlling for age and sex. Conclusions: Findings suggest that benefit
      finding is associated with internalizing mental health symptoms, pain outcomes,
      and quality of life in youth with chronic pain. Future research examining this
      construct is warranted.

PMID- 29048520
TI  - Pain Acceptance as a Predictor of Medical Utilization and School Absenteeism in
      Adolescents With Chronic Pain.
AB  - Objective: Identifying factors contributing to high medical utilization and
      productivity loss is important, given the high cost of pediatric chronic pain.
      The current study examined chronic pain acceptance as a predictor of medical
      utilization and school absenteeism in adolescents with chronic pain. Methods: In
      all, 122 adolescents (aged 12-21 years) with chronic pain and their
      parents/guardians completed questionnaires assessing medical visits (past 6
      months), medication usage, and number of school absences (past month). Homebound
      school status was also reported. Adolescents completed the Chronic Pain
      Acceptance Questionnaire and pain intensity ratings, and underwent a diagnostic
      psychological evaluation. Results: Multivariate generalized linear model analyses
      indicated lower pain acceptance predicted increased inpatient hospitalizations
      and higher number of opioid and nonopioid prescription medications, controlling
      for pain intensity, age, and sex. Pain acceptance was not associated with
      outpatient consultations or number of nonprescription medications. Exploratory
      moderation analyses indicated lower pain acceptance significantly predicted
      increased emergency department visits and inpatient hospitalizations for patients
      diagnosed with an internalizing psychological disorder. Patients in homebound
      schooling reported low pain acceptance and for those in school full-time, linear
      regression indicated lower pain acceptance significantly predicted higher number
      of school absences. Conclusions: Findings suggest that lower pain acceptance
      contributes to the use of higher-level medical care (especially for adolescents
      with internalizing disorders) and increased productivity loss owing to school
      absences or homebound school status. Clinical implications exist for recommending
      acceptance-based interventions for pain acceptance promotion and continued
      development of cost-effective, easily disseminated acceptance-based therapy
      modules to curb the economic burden of chronic pain.

PMID- 29048521
TI  - Sclerostin and chronic kidney disease: the assay impacts what we (thought to)
      know.
AB  - Background: Sclerostin, a 22-kDa protein secreted by osteocytes, acts as a potent
      inhibitor of osteoblast activity. In chronic kidney disease (CKD), sclerostin is
      a putative driver of the bone-vascular axis. However, large discrepancies between
      sclerostin assays have been described. Methods: We compared four different assays
      [Biomedica (BM), TecoMedical (TE), R&D (RD) and MesoScaleDiscovery (MSD)] in an
      analytical study and addressed the question whether bioassay choice affects the
      correlation between circulating sclerostin and clinical and biochemical
      determinants. Circulating sclerostin levels were determined in 39 prevalent
      dialysis patients and 82 non-dialysis patients referred for glomerular filtration
      rate measurement. Results: In the 82 non-dialysis patients, we observed large
      differences in median (interquartile range) sclerostin concentrations (in pg/mL):
      BM, 984 [interquartile range (IQR) 648]; TE, 629 (IQR 237); RD, 154 (IQR 84) and
      MSD, 36 (IQR 19). The concordance correlation coefficient between assays was poor
      (0.1-0.44). The same discrepancies were observed in dialysis patients. A
      significant negative rank correlation was found between glomerular filtration
      rate and sclerostin measured by BM and TE but not by MSD and RD. Associations
      between sclerostin and age, gender, weight or parathormone were also different
      according to the assay considered. Conclusions: Clinical inference relating
      sclerostin levels found in the general, CKD and dialysis populations is largely
      influenced by the assay used to measure this biomarker.

PMID- 29048523
TI  - T-cadherin gene variants are associated with nephropathy in subjects with type 1
      diabetes.

PMID- 29048522
TI  - Screening for atrial fibrillation: a European Heart Rhythm Association (EHRA)
      consensus document endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart
      Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y
      Electrofisiologia (SOLAECE).

PMID- 29048524
TI  - Krait: an ultrafast tool for genome-wide survey of microsatellites and primer
      design.
AB  - Summary: Microsatellites are found to be related with various diseases and widely
      used in population genetics as genetic markers. However, it remains a challenge
      to identify microsatellite from large genome and screen microsatellites for
      primer design from a huge result dataset. Here, we present Krait, a robust and
      flexible tool for fast investigation of microsatellites in DNA sequences. Krait
      is designed to identify all types of perfect or imperfect microsatellites on a
      whole genomic sequence, and is also applicable to identification of compound
      microsatellites. Primer3 was seamlessly integrated into Krait so that users can
      design primer for microsatellite amplification in an efficient way. Additionally,
      Krait can export microsatellite results in FASTA or GFF3 format for further
      analysis and generate statistical report as well as plotting. Availability and
      implementation: Krait is freely available at https://github.com/lmdu/krait under
      GPL2 License, implemented in C and Python, and supported on Windows, Linux and
      Mac operating systems. Contact: chizhang_swmu@126.com. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29048525
TI  - Genome-Based Analyses of Six Hexacorallian Species Reject the "Naked Coral"
      Hypothesis.
AB  - Scleractinian corals are the foundation species of the coral-reef ecosystem.
      Their calcium carbonate skeletons form extensive structures that are home to
      millions of species, making coral reefs one of the most diverse ecosystems of our
      planet. However, our understanding of how reef-building corals have evolved the
      ability to calcify and become the ecosystem builders they are today is hampered
      by uncertain relationships within their subclass Hexacorallia. Corallimorpharians
      have been proposed to originate from a complex scleractinian ancestor that lost
      the ability to calcify in response to increasing ocean acidification, suggesting
      the possibility for corals to lose and gain the ability to calcify in response to
      increasing ocean acidification. Here, we employed a phylogenomic approach using
      whole-genome data from six hexacorallian species to resolve the evolutionary
      relationship between reef-building corals and their noncalcifying relatives.
      Phylogenetic analysis based on 1,421 single-copy orthologs, as well as gene
      presence/absence and synteny information, converged on the same topologies,
      showing strong support for scleractinian monophyly and a corallimorpharian sister
      clade. Our broad phylogenomic approach using sequence-based and sequence
      independent analyses provides unambiguous evidence for the monophyly of
      scleractinian corals and the rejection of corallimorpharians as descendants of a
      complex coral ancestor.

PMID- 29048526
TI  - Comparative Transcriptomics of Steinernema and Caenorhabditis Single Embryos
      Reveals Orthologous Gene Expression Convergence during Late Embryogenesis.
AB  - Cells express distinct sets of genes in a precise spatio-temporal manner during
      embryonic development. There is a wealth of information on the deterministic
      embryonic development of Caenorhabditis elegans, but much less is known about
      embryonic development in nematodes from other taxa, especially at the molecular
      level. We are interested in insect pathogenic nematodes from the genus
      Steinernema as models of parasitism and symbiosis as well as a satellite model
      for evolution in comparison to C. elegans. To explore gene expression differences
      across taxa, we sequenced the transcriptomes of single embryos of two Steinernema
      species and two Caenorhabditis species at 11 stages during embryonic development
      and found several interesting features. Our findings show that zygotic
      transcription initiates at different developmental stages in each species, with
      the Steinernema species initiating transcription earlier than Caenorhabditis. We
      found that ortholog expression conservation during development is higher at the
      later embryonic stages than at the earlier ones. The surprisingly higher
      conservation of orthologous gene expression in later embryonic stages strongly
      suggests a funnel-shaped model of embryonic developmental gene expression
      divergence in nematodes. This work provides novel insight into embryonic
      development across distantly related nematode species and demonstrates that the
      mechanisms controlling early development are more diverse than previously thought
      at the transcriptional level.

PMID- 29048527
TI  - The Evolution of Dark Matter in the Mitogenome of Seed Beetles.
AB  - Animal mitogenomes are generally thought of as being economic and optimized for
      rapid replication and transcription. We use long-read sequencing technology to
      assemble the remarkable mitogenomes of four species of seed beetles. These are
      the largest circular mitogenomes ever assembled in insects, ranging from 24,496
      to 26,613 bp in total length, and are exceptional in that some 40% consists of
      non-coding DNA. The size expansion is due to two very long intergenic spacers
      (LIGSs), rich in tandem repeats. The two LIGSs are present in all species but
      vary greatly in length (114-10,408 bp), show very low sequence similarity,
      divergent tandem repeat motifs, a very high AT content and concerted length
      evolution. The LIGSs have been retained for at least some 45 my but must have
      undergone repeated reductions and expansions, despite strong purifying selection
      on protein coding mtDNA genes. The LIGSs are located in two intergenic sites
      where a few recent studies of insects have also reported shorter LIGSs (>200 bp).
      These sites may represent spaces that tolerate neutral repeat array expansions
      or, alternatively, the LIGSs may function to allow a more economic translational
      machinery. Mitochondrial respiration in adult seed beetles is based almost
      exclusively on fatty acids, which reduces the need for building complex I of the
      oxidative phosphorylation pathway (NADH dehydrogenase). One possibility is thus
      that the LIGSs may allow depressed transcription of NAD genes. RNA sequencing
      showed that LIGSs are partly transcribed and transcriptional profiling suggested
      that all seven mtDNA NAD genes indeed show low levels of transcription and co
      regulation of transcription across sexes and tissues.

PMID- 29048528
TI  - Pervasive Transcription of Mitochondrial, Plastid, and Nucleomorph Genomes across
      Diverse Plastid-Bearing Species.
AB  - Organelle genomes exhibit remarkable diversity in content, structure, and size,
      and in their modes of gene expression, which are governed by both organelle- and
      nuclear-encoded machinery. Next generation sequencing (NGS) has generated
      unprecedented amounts of genomic and transcriptomic data, which can be used to
      investigate organelle genome transcription. However, most of the available
      eukaryotic RNA-sequencing (RNA-seq) data are used to study nuclear transcription
      only, even though large numbers of organelle-derived reads can typically be mined
      from these experiments. Here, we use publicly available RNA-seq data to assess
      organelle genome transcription in 59 diverse plastid-bearing species. Our RNA
      mapping analyses unraveled pervasive (full or near-full) transcription of
      mitochondrial, plastid, and nucleomorph genomes. In all cases, 85% or more of the
      organelle genome was recovered from the RNA data, including noncoding (intergenic
      and intronic) regions. These results reinforce the idea that organelles
      transcribe all or nearly all of their genomic material and are dependent on post
      transcriptional processing of polycistronic transcripts. We explore the
      possibility that transcribed intergenic regions are producing functional
      noncoding RNAs, and that organelle genome noncoding content might provide raw
      material for generating regulatory RNAs.

PMID- 29048529
TI  - The Rhizome of Lokiarchaeota Illustrates the Mosaicity of Archaeal Genomes.
AB  - Genome remodeling and exchange of sequences are widespread in the prokaryotic
      world and mosaic genomes challenge the classification of prokaryotes, which
      cannot be properly achieved in terms of a single gene or group of genes. Here, we
      studied individually the gene collection of the archaic microorganism
      Lokiarchaeum sp., suggested as an archaeal host close to the emergence of the
      eukaryotes. The network or rhizome of all Lokiarchaeum sp. genes revealed that
      the genomic repertoire is mainly composed of genes from archaeal (~36%) and
      bacterial origin (~28%), distantly followed by components of eukaryotic origin
      (~2%). Thirty-three percent of genes were unique to this species (ORFans). The
      mosaicity of archaea was also supported by studying Methanomassiliicoccus
      luminyensis, an archaea from the gut, in which 67% of the genomic repertoire
      arised from archaea and 22% from bacteria. Our results illustrate the intricate
      evolutionary relationships of the archaeal genome repertoire and highlight the
      rhizome-like processes of evolution in archaea, their mosaicity, and chimeric
      origin composed of different domains of life, questioning the reality of a tree
      of life.

PMID- 29048530
TI  - Population Genomic Analysis of a Pitviper Reveals Microevolutionary Forces
      Underlying Venom Chemistry.
AB  - Venoms are among the most biologically active secretions known, and are commonly
      believed to evolve under extreme positive selection. Many venom gene families,
      however, have undergone duplication, and are often deployed in doses vastly
      exceeding the LD50 for most prey species, which should reduce the strength of
      positive selection. Here, we contrast these selective regimes using snake venoms,
      which consist of rapidly evolving protein formulations. Though decades of
      extensive studies have found that snake venom proteins are subject to strong
      positive selection, the greater action of drift has been hypothesized, but never
      tested. Using a combination of de novo genome sequencing, population genomics,
      transcriptomics, and proteomics, we compare the two modes of evolution in the
      pitviper, Protobothrops mucrosquamatus. By partitioning selective constraints and
      adaptive evolution in a McDonald-Kreitman-type framework, we find support for
      both hypotheses: venom proteins indeed experience both stronger positive
      selection, and lower selective constraint than other genes in the genome.
      Furthermore, the strength of selection may be modulated by expression level, with
      more abundant proteins experiencing weaker selective constraint, leading to the
      accumulation of more deleterious mutations. These findings show that snake venoms
      evolve by a combination of adaptive and neutral mechanisms, both of which explain
      their extraordinarily high rates of molecular evolution. In addition to positive
      selection, which optimizes efficacy of the venom in the short term, relaxed
      selective constraints for deleterious mutations can lead to more rapid turnover
      of individual proteins, and potentially to exploration of a larger venom
      phenotypic space.

PMID- 29048531
TI  - Origin and Spread of Spliceosomal Introns: Insights from the Fungal Clade
      Zymoseptoria.
AB  - Spliceosomal introns are a key feature of eukaryote genome architecture and have
      been proposed to originate from selfish group II introns from an endosymbiotic
      bacterium, that is, the ancestor of mitochondria. However, the mechanisms
      underlying the wide spread of spliceosomal introns across eukaryotic genomes have
      been obscure. In this study, we characterize the dynamic evolution of
      spliceosomal introns in the fungal genus Zymoseptoria at different evolutionary
      scales, that is, within a genome, among conspecific strains within species, and
      between different species. Within the genome, spliceosomal introns can
      proliferate in unrelated genes and intergenic regions. Among conspecific strains,
      spliceosomal introns undergo rapid turnover (gains and losses) and frequent
      sequence exchange between geographically distinct strains. Furthermore,
      spliceosomal introns could undergo introgression between distinct species, which
      can further promote intron invasion and proliferation. The dynamic invasion and
      proliferation processes of spliceosomal introns resemble the life cycles of
      mobile selfish (group I/II) introns, and these intron movements, at least in
      part, account for the dramatic processes of intron gain and intron loss during
      eukaryotic evolution.

PMID- 29048532
TI  - Lightning-fast genome variant detection with GROM.
AB  - Current human whole genome sequencing projects produce massive amounts of data,
      often creating significant computational challenges. Different approaches have
      been developed for each type of genome variant and method of its detection,
      necessitating users to run multiple algorithms to find variants. We present
      Genome Rearrangement OmniMapper (GROM), a novel comprehensive variant detection
      algorithm accepting aligned read files as input and finding SNVs, indels,
      structural variants (SVs), and copy number variants (CNVs). We show that GROM
      outperforms state-of-the-art methods on 7 validated benchmarks using 2 whole
      genome sequencing (WGS) data sets. Additionally, GROM boasts lightning-fast run
      times, analyzing a 50* WGS human data set (NA12878) on commonly available
      computer hardware in 11 minutes, more than an order of magnitude (up to 72 times)
      faster than tools detecting a similar range of variants. Addressing the needs of
      big data analysis, GROM combines in 1 algorithm SNV, indel, SV, and CNV
      detection, providing superior speed, sensitivity, and precision. GROM is also
      able to detect CNVs, SNVs, and indels in non-paired-read WGS libraries, as well
      as SNVs and indels in whole exome or RNA sequencing data sets.

PMID- 29048533
TI  - Parallel sequencing lives, or what makes large sequencing projects successful.
AB  - T47D_rep2 and b1913e6c1_51720e9cf were 2 Hi-C samples. They were born and
      processed at the same time, yet their fates were very different. The life of
      b1913e6c1_51720e9cf was simple and fruitful, while that of T47D_rep2 was full of
      accidents and sorrow. At the heart of these differences lies the fact that
      b1913e6c1_51720e9cf was born under a lab culture of Documentation, Automation,
      Traceability, and Autonomy and compliance with the FAIR Principles. Their lives
      are a lesson for those who wish to embark on the journey of managing high
      throughput sequencing data.

PMID- 29048535
TI  - Symposium Overview: Integrating Cognitive, Motivational, and Sensory Biases
      Underlying Acoustic- and Multimodal-Based Mate Choice.
AB  - The goal of this symposium "Integrating Cognitive, Motivational and Sensory
      Biases Underlying Acoustic and Multimodal-Based Mate Choice" was to build a more
      complete framework in which to understand the mate choice brain. The
      presentations and papers within this symposium incorporate studies of
      motivational, cognitive, sensory and salience components of mate choice and
      highlight future directions that are needed to understand the biological basis of
      mate choice decision-making.

PMID- 29048534
TI  - Neural Circuitry for Target Selection and Action Selection in Animal Behavior.
AB  - Animal behaviorists have long strived for a comprehensive understanding of the
      proximate and ultimate causes of complex behavior, and we propose that recent
      advances in neurobiology can help reshape or clarify this behavior-oriented
      understanding. We begin with an overview of current views of neural circuit
      mechanisms that mediate target selection and action selection. In target
      selection, different stimuli compete for priority in sensory-motor processing.
      Action selection is the process by which multiple possible motor actions compete
      for priority in a manner which balances the needs of the animal with
      opportunities or threats in the environment. We next discuss spatial and temporal
      aspects of target and action selection, highlighting how neurophysiological
      responses to complex displays depend on spatial and temporal components of
      multisensory stimuli. We use two examples-(1) spatial attention as an example of
      target selection in the vertebrate midbrain and (2) goal-directed locomotion as
      an example of action selection in the insect central complex-to further clarify
      neural circuit dynamics as they relate to target and action selection, and their
      interaction. We suggest that a deeper understanding of neural circuit properties
      will introduce new hypotheses into behavioral studies, especially those aimed at
      understanding the evolution of complex displays based on receiver sensory biases.
      Additionally, knowledge of neural circuit properties can elucidate ways in which
      current context and previous experience can together modify neural circuit
      dynamics to produce complex context-dependent behavioral responses that often
      characterize animal behavior.

PMID- 29048536
TI  - Neurobiology of Female Mate Choice in Frogs: Auditory Filtering and Valuation.
AB  - Mate choice is a decision making process with profound implication for the
      reproductive success of both the sender and the chooser. Preferences for
      conspecific over heterospecific males and for some conspecifics over others are
      typically mediated by a female's response to signals produced by males. And
      although one can experimentally describe a female's preference function, there is
      relatively little understood about the neural mechanisms mediating these
      preferences. In anurans, mating preferences have often been explained in terms of
      sensory biases. Indeed, in the tungara frog (Physalaemus pustulosus), the
      auditory system appears to act as a filter for conspecific calls. However,
      auditory responses are not good predictors of intraspecific mating preferences in
      tungara frogs. Rather, neural activity in the preoptic area, which can be gated
      by estradiol, is a better predictor of mating preferences. A similar pattern
      holds in spadefoot toads (Spea bombifrons): the preoptic area, but not the
      auditory midbrain, integrates physiological cues in its response to mating calls
      in a pattern that predicts preferences. Neuroanatomically, the anuran preoptic
      area is poised to mediate forebrain influences on auditory response of the
      midbrain and it has descending projections to the medulla and spinal cord that
      could directly influence motor responses. Indeed, lesions of the preoptic area
      abolish phonotaxis. A role for the preoptic area in mating preferences is
      supported by studies in mammals that show the preoptic area is required for the
      expression of preferences. Further, activity of the preoptic area correlates with
      mating preference in fish. This leads to a model for the neurobiological
      mechanisms of mate choice, in which sensory systems filter relevant signals from
      irrelevant ones, but the preoptic area assigns value to the range of relevant
      signals.

PMID- 29048537
TI  - Group Living and Male Dispersal Predict the Core Gut Microbiome in Wild Baboons.
AB  - The mammalian gut microbiome plays a profound role in the physiology, metabolism,
      and overall health of its host. However, biologists have only a nascent
      understanding of the forces that drive inter-individual heterogeneity in gut
      microbial composition, especially the role of host social environment. Here we
      used 178 samples from 78 wild yellow baboons (Papio cynocephalus) living in two
      social groups to test how host social context, including group living, social
      interactions within groups, and transfer between social groups (e.g., dispersal)
      predict inter-individual variation in gut microbial alpha and beta diversity. We
      also tested whether social effects differed for prevalent "core" gut microbial
      taxa, which are thought to provide primary functions to hosts, versus rare "non
      core" microbes, which may represent relatively transient environmental
      acquisitions. Confirming prior studies, we found that each social group harbored
      a distinct gut microbial community. These differences included both non-core and
      core gut microbial taxa, suggesting that these effects are not solely driven by
      recent gut microbial exposures. Within social groups, close grooming partners had
      more similar core microbiomes, but not non-core microbiomes, than individuals who
      rarely groomed each other, even controlling for kinship and diet similarity
      between grooming partners. Finally, in support of the idea that the gut
      microbiome can be altered by current social context, we found that the longer an
      immigrant male had lived in a given social group, the more closely his gut
      microbiome resembled the gut microbiomes of the group's long-term residents.
      Together, these results reveal the importance of a host's social context in
      shaping the gut microbiome and shed new light onto the microbiome-related
      consequences of male dispersal.

PMID- 29048539
TI  - Indexcov: fast coverage quality control for whole-genome sequencing.
AB  - The BAM and CRAM formats provide a supplementary linear index that facilitates
      rapid access to sequence alignments in arbitrary genomic regions. Comparing
      consecutive entries in a BAM or CRAM index allows one to infer the number of
      alignment records per genomic region for use as an effective proxy of sequence
      depth in each genomic region. Based on these properties, we have developed
      indexcov, an efficient estimator of whole-genome sequencing coverage to rapidly
      identify samples with aberrant coverage profiles, reveal large-scale chromosomal
      anomalies, recognize potential batch effects, and infer the sex of a sample.
      Indexcov is available at https://github.com/brentp/goleft under the MIT license.

PMID- 29048538
TI  - Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction
      and activation.
AB  - Since induced regulatory T cells (iTregs) can be produced in a large quantity in
      vitro, these cells are expected to be clinically useful to induce immunological
      tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression
      in iTregs is, however, unstable due to the lack of demethylation of the CpG
      island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To
      facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD)
      of the ten-eleven translocation (TET) protein, which catalyzes the steps of the
      iterative demethylation of 5-methylcytosine. TET-CD over-expression in iTregs
      resulted in partial demethylation of CNS2 and stable Foxp3 expression. We also
      discovered that TET expression was enhanced under low oxygen (5%) culture
      conditions, which facilitated CNS2 DNA demethylation and stabilization of Foxp3
      expression in a TET2- and TET3-dependent manner. In combination with vitamin C
      treatment, which has been reported to enhance TET catalytic activity, iTregs
      generated under low oxygen conditions retained more stable Foxp3 expression in
      vitro and in vivo and exhibited stronger suppression activity in a colitis model
      compared with untreated iTregs. Our data indicate that the induction and
      activation of TET enzymes in iTregs would be an effective method for Treg
      mediated adoptive immunotherapy.

PMID- 29048540
TI  - Long-read sequencing of the coffee bean transcriptome reveals the diversity of
      full-length transcripts.
AB  - Polyploidization contributes to the complexity of gene expression, resulting in
      numerous related but different transcripts. This study explored the transcriptome
      diversity and complexity of the tetraploid Arabica coffee (Coffea arabica) bean.
      Long-read sequencing (LRS) by Pacbio Isoform sequencing (Iso-seq) was used to
      obtain full-length transcripts without the difficulty and uncertainty of assembly
      required for reads from short-read technologies. The tetraploid transcriptome was
      annotated and compared with data from the sub-genome progenitors. Caffeine and
      sucrose genes were targeted for case analysis. An isoform-level tetraploid coffee
      bean reference transcriptome with 95 995 distinct transcripts (average 3236 bp)
      was obtained. A total of 88 715 sequences (92.42%) were annotated with BLASTx
      against NCBI non-redundant plant proteins, including 34 719 high-quality
      annotations. Further BLASTn analysis against NCBI non-redundant nucleotide
      sequences, Coffea canephora coding sequences with UTR, C. arabica ESTs, and Rfam
      resulted in 1213 sequences without hits, were potential novel genes in coffee.
      Longer UTRs were captured, especially in the 5?UTRs, facilitating the
      identification of upstream open reading frames. The LRS also revealed more and
      longer transcript variants in key caffeine and sucrose metabolism genes from this
      polyploid genome. Long sequences (>10 kilo base) were poorly annotated. LRS
      technology shows the limitation of previous studies. It provides an important
      tool to produce a reference transcriptome including more of the diversity of full
      length transcripts to help understand the biology and support the genetic
      improvement of polyploid species such as coffee.

PMID- 29048542
TI  - Adolescent Information Management and Parental Knowledge in Non-Latino White and
      Latino Youth Managing Type 1 Diabetes.
AB  - Objectives: The objective of this study is to examine associations between
      adolescents' regulation of information about their type 1 diabetes (adolescent
      disclosure, secrecy), parental knowledge about their adolescent's diabetes
      management, diabetes outcomes (adherence, HbA1c), and depressive symptoms in Non
      Latino White and Latino families. Methods: In all, 118 adolescents (56 = Latino,
      62 = Non-Latino White) completed surveys of disclosure to and secrecy from
      parents, parental knowledge of adolescent diabetes management, adherence, and
      depressive symptoms, and mothers completed measures of maternal knowledge and
      adolescent adherence. Glycemic control was extracted from medical records.
      Adolescents also completed structured interviews about parental knowledge about
      their diabetes-related problems. Results: Interviews revealed that adolescent
      disclosure is the primary method by which parents gain knowledge about adolescent
      diabetes management problems. Adolescent disclosure to and secrecy from parents
      were uniquely associated with diabetes management and depressive symptoms
      independent of parental knowledge across ethnic groups; maternal reports of
      knowledge about her adolescent's diabetes care activities were associated with
      diabetes management independent of adolescent disclosure and secrecy.
      Conclusions: Adolescent information management strategies are a primary means by
      which parents gain knowledge about diabetes, which may facilitate more effective
      management.

PMID- 29048543
TI  - Cardiac tamponade in systemic lupus erythematosus.
AB  - Background: Cardiac tamponade is a rare but life-threatening complication of
      systemic lupus erythematosus (SLE). Aims/Objectives: To describe incidence, risk
      factors and treatment of cardiac tamponade in a large cohort of Indian patients
      with SLE. Methods: This retrospective study was conducted at the Department of
      Rheumatology, IPGMER, Kolkata, India from May 2014 to December 2016 on admitted
      patients with SLE. Lupus-related serositis was diagnosed after excluding other
      causes, such as infection, malignancy or heart failure. Results: Of 409 patients
      with SLE, pericarditis was diagnosed in 25.4% (104/409) and cardiac tamponade in
      5.9% (24/409). Tamponade was the presenting feature of SLE in 50% (12/24).
      Tamponade occurred in 77.8% (14/18) of large effusions and in 11.63% (10/86) of
      small-to-moderate effusions. The commonest autoantibody in serum and pericardial
      fluid was anti-nucleosme antibody. Large pericardial effusion (>20 mm) (Odd's
      ratio (OR): 93.2, 95% confidence interval (CI): 11.1-782.5, P < 0.001) predicted
      tamponade. In the subset of patients with small-to-moderate sized pericardial
      effusion, tamponade was associated with pleuritis (OR: 44.5, 95% CI: 1.6-1243, P
      = 0.025), anti-nucleosome antibody (OR: 42.9, 95% CI: 1.6-1176, P = 0.026) and
      size of pericardial effusion (OR: 1.36, 95% CI: 1.04-1.76, P = 0.025). Repeated
      pericardiocentesis was required in 3 patients and one needed surgical
      intervention. Immunosuppressives used were: prednisolone with monthly intravenous
      cyclophosphamide (in 33.33%) and intravenous methylprednisolone with monthly
      cyclophosphamide (in 50%). Conclusions: Pleuritis, anti-nucleosome antibody and
      size of pericardial effusion predicted development of tamponade. High dose
      immunosuppression (methylprednisolone and IV cyclophosphamide) alleviated need
      for surgery in majority.

PMID- 29048544
TI  - Valproic acid attenuates the risk of acute respiratory failure in patients with
      subarachnoid hemorrhage.
AB  - Background: Valproic acid (VPA) has shown potent anti-inflammatory effect and
      attenuates acute lung injury. Aim: To determine whether the use of VPA is
      associated with a decreased risk of acute respiratory failure (ARF) in patients
      with subarachnoid hemorrhage (SAH). Design: The Taiwan National Health Insurance
      Research Database was used to analyse all patients newly diagnosed with SAH from
      2000 to 2010. The VPA users were matched for age, gender and index date in 1:2
      ratios with randomly selected non-VPA users as a comparison group. Methods:
      Multivariate Cox regression was used to identify the predictors of ARF and to
      compare the incidence rates of ARF among SAH patients using and not using VPA.
      Results: The study cohort included 16 228 newly diagnosed SAH patients, from
      which 521 VPA users and 1042 matched non-VPA-exposed individuals were selected.
      In the VPA-treated cohort and the non-VPA-treated cohort, 117 and 289 patients
      developed ARF, respectively. Any use of VPA was associated with a 16% decreased
      risk of ARF requiring mechanical ventilation in 30-day tracking of the SAH
      patients (adjusted hazard ratio [HR], 0.840, 95% confidence interval [CI], 0.676
      0.945). Age, sepsis and pneumonia were identified as independent predictors of
      ARF in patients with SAH. After stratification, VPA users showed a lower risk of
      ARF among SAH patients complicated with pneumonia compared with non-users of VPA
      (adjusted HR, 0.816, 95% CI, 0.652-0.921). Conclusions: Any use of VPA was
      associated with a reduced risk of ARF in patients with SAH. VPA may be beneficial
      for decreasing the risk of pneumonia-induced ARF in patients with SAH.

PMID- 29048546
TI  - Housing, psychosocial and adherence counseling among HIV+ persons in Ghana.
AB  - As part of providing comprehensive HIV/AIDS services, the Ghana National AIDS
      Control Programme (NACP) and Ministry of Health recommend that Persons Living
      with HIV/AIDS (PLWHAs) receive psychosocial support and follow-up visits that
      ensure medical and drug adherence assistance. The successful implementation of
      these support services requires patients to have stable and quality housing, yet
      studies that examine associations between housing, psychosocial support, and
      adherence counseling among PLWHAs in Ghana and sub-Saharan Africa are limited.
      Data were collected from 605 PLWHAs attending check-up and receiving Anti
      Retroviral Therapy (ART) from both Atua Government Hospital and St. Martin's de
      Porres Hospital, located in the Manya Krobo district. Results show significant
      relationships between housing and access to psychosocial counseling and support.
      Specifically, respondents with stable homes and quality housing were
      significantly more likely to receive psychosocial counseling and support,
      compared to those without stable and quality housing. It is important for policy
      makers to consider housing as an important element of psychosocial counseling and
      care.

PMID- 29048547
TI  - Perspectives on Integrating Genetic and Physical Explanations of Evolution and
      Development: An Introduction to the Symposium.
AB  - In the 20th century, genetic explanatory approaches became dominant in both
      developmental and evolutionary biological research. By contrast, physical
      approaches, which appeal to properties such as mechanical forces, were largely
      relegated to the margins, despite important advances in modeling. Recently, there
      have been renewed attempts to find balanced viewpoints that integrate both
      biological physics and molecular genetics into explanations of developmental and
      evolutionary phenomena. Here we introduce the 2017 SICB symposium "Physical and
      Genetic Mechanisms for Evolutionary Novelty" that was dedicated to exploring
      empirical cases where both biological physics and developmental genetic
      considerations are crucial. To further contextualize these case studies, we offer
      two theoretical frameworks for integrating genetic and physical explanations:
      combining complementary perspectives and comprehensive unification. We conclude
      by arguing that intentional reflection on conceptual questions about
      investigation, explanation, and integration is critical to achieving significant
      empirical and theoretical advances in our understanding of how novel forms
      originate across the tree of life.

PMID- 29048548
TI  - Intravenous leiomyomatosis with intracardiac extension.

PMID- 29048550
TI  - Altered Neurophysiological Processing of Auditory Attention in Preschool Children
      With Sickle Cell Disease.
AB  - Objective: Sickle cell disease (SCD) is a genetic red blood cell disorder that
      often leads to stroke and executive dysfunction in school-age children and
      adults. This study aimed to characterize the development of the neural correlates
      of selective attention, an early component of executive function, in preschool
      children with SCD. Methods: Auditory event-related potentials (ERPs) were
      recorded while children attended to a story stream in one ear and ignored a
      second story in the other ear interchangeably. In total, 12 patients (mean age =
      5.5, 7 males) and 22 typically developing children (mean age = 4.4, 10 males)
      were included in the final analyses. Results: By 100 ms, more positive ERP
      amplitudes were observed for attended relative to unattended stimuli in typically
      developing children but not those with SCD, suggesting deficits in the ability to
      focus attention. Reduced attention effects were associated with lower performance
      intellectual quotient. Conclusion: There are deficits in early attention
      modulation in young children with SCD.

PMID- 29048551
TI  - Rapid Screening of Risk in Pediatric Headache: Application of the Pediatric Pain
      Screening Tool.
AB  - Objective: The current study examined the application of a screening tool to
      identify biopsychosocial risk factors and derive prognostic risk groups in
      children and adolescents with headache pain. Methods: Youth (n = 242, 8-17 years,
      75.6% female) presenting for evaluation at a tertiary pediatric headache clinic
      completed the nine-item Pediatric Pain Screening Tool (PPST) as well as measures
      of functional disability, pain catastrophizing, fear of pain, anxiety, and
      depressive symptoms. In addition, 119 patients reported on functional disability
      at 2-month follow-up. Results: The PPST demonstrated discriminant validity that
      ranged from fair to good for identifying significant disability and high
      emotional distress. Receiver operating characteristic curve analyses indicated
      that established cutoff scores were appropriate for the current sample, and thus
      participants were classified into low-risk (21%), medium-risk (31%), and high
      risk (48%) groups. Only 1-6% of patients who met reference standard case status
      for disability and emotional distress were classified as low risk, whereas 64-90%
      of patients who met reference standard case status were classified as high risk,
      suggesting robust stratification. Conclusions: The nine-item PPST may be a useful
      tool for efficiently identifying young patients with headache who are at risk of
      poor outcomes, and effectively classifying them into risk groups that could drive
      stratified treatment directly targeting patient needs.

PMID- 29048549
TI  - Curcumin sensitizes pancreatic cancer cells to gemcitabine by attenuating PRC2
      subunit EZH2, and the lncRNA PVT1 expression.
AB  - Development of resistance to chemotherapeutic drugs is a major challenge in the
      care of patients with pancreatic ductal adenocarcinoma (PDAC). Acquired
      resistance to chemotherapeutic agents in PDAC has been linked to a subset of
      cancer cells termed 'cancer stem cells' (CSCs). Therefore, an improved
      understanding of the molecular events underlying the development of pancreatic
      CSCs is required to identify new therapeutic targets to overcome chemoresistance.
      Accumulating evidence indicates that curcumin, a phenolic compound extracted from
      turmeric, can overcome de novo chemoresistance and re-sensitize tumors to various
      chemotherapeutic agents. However, the underlying mechanisms for curcumin-mediated
      chemosensitization remain unclear. The Enhancer of Zeste Homolog-2 (EZH2) subunit
      of Polycomb Repressive Complex 2 (PRC2) was recently identified as a key player
      regulating drug resistance. EZH2 mediates interaction with several long non
      coding RNAs (lncRNAs) to modulate epithelial-mesenchymal transition and cancer
      stemness, phenomena commonly associated with drug resistance. Here, we report the
      re-sensitization of chemoresistant PDAC cells by curcumin through the inhibition
      of the PRC2-PVT1-c-Myc axis. Using gemcitabine-resistant PDAC cell lines, we
      found that curcumin sensitized chemoresistant cancer cells by inhibiting the
      expression of the PRC2 subunit EZH2 and its related lncRNA PVT1. Curcumin was
      also found to prevent the formation of spheroids, a hallmark of CSCs, and to down
      regulate several self-renewal driving genes. In addition, we confirmed our in
      vitro findings in a xenograft mouse model where curcumin inhibited gemcitabine
      resistant tumor growth. Overall, this study indicates clinical relevance for
      combining curcumin with chemotherapy to overcome chemoresistance in PDAC.

PMID- 29048552
TI  - Psychometric Evaluation of the IBD-Specific Anxiety Scale: A Novel Measure of
      Disease-Related Anxiety for Adolescents With IBD.
AB  - : Anxiety related to pediatric inflammatory bowel disease (IBD) is a common
      comorbidity; yet, this construct is understudied because of lack of available
      valid measurement. Objective: The present study will report the preliminary
      validation of the 20-item IBD-Specific Anxiety Scale (IBD-SAS) in a large,
      geographically diverse sample of adolescents aged 12-18 years with IBD. Method: A
      total of 281 adolescents, ages 12-18 (M = 14.8, SD = 1.78; 51% male), completed
      the IBD-SAS along with measures of IBD-related quality of life, anxiety,
      depressive symptoms, and disease activity. Factor structure was assessed using
      exploratory and confirmatory factor analyses (EFA and CFA). Results: EFA (Sample
      1; n = 141) yielded one-, two-, three- and four-factor models. The CFA (Sample 2;
      n = 140) demonstrated that a four-factor model was superior to three- and two
      factor model for the amended scale. In total, the IBD-SAS showed excellent
      internal consistency (Cronbach's alpha = .95) and was most strongly associated
      with health-related quality of life. Moderate to strong associations were
      observed between IBD-SAS and general measures of anxiety and depressive symptoms,
      and IBD disease activity providing additional support that health-specific
      anxiety is a valid and distinct construct. Conclusions: Based on the results of
      this study, the IBD-SAS displayed adequate psychometric properties and can
      meaningfully contribute to the assessment of IBD-specific anxiety in adolescents
      diagnosed with IBD, thus filling an empirical and clinical need in this
      population.

PMID- 29048553
TI  - Are Preschoolers Meeting the Mark? Comparing the Dietary, Activity, and Sleep
      Behaviors of Preschoolers With Obesity to National Recommendations.
AB  - Objective: National health organizations and expert committees have issued
      recommendations for health behaviors related to obesity risk. Behavioral and
      family-based weight management interventions for preschoolers often target
      improving adherence to these recommendations, but it is unknown how the health
      behaviors of preschoolers with obesity enrolled in weight control treatments
      (WCTs) compare with these guidelines. In this study, the dietary intake,
      activity, and sleep behaviors of preschoolers with obesity enrolled in a family
      based behavioral WCT are described and compared with national health behavior
      recommendations. Methods: Health behaviors of 151 preschoolers with obesity (M
      age = 4.60, SD = 0.93) enrolled in a clinical trial of a weight management
      program were measured at baseline through caregiver-report questionnaires, three
      24-hr dietary recalls, and accelerometers. Results: In total, 70% of the sample
      exceeded daily caloric recommendations, only 10 and 5% met recommendations for
      fruit and vegetable intake, respectively, and only 30% met the recommendation of
      consuming no sugar-sweetened beverages. The majority of the sample met the daily
      recommendations for 60 min of moderate-to-vigorous activity (80%), < 2 hr of
      screen time (68%), and sleep duration (70%). Conclusions: Behavioral weight
      management interventions for preschoolers with obesity should target the health
      behaviors where children are not meeting recommendations.

PMID- 29048554
TI  - Social Risk and Resilience Factors in Adolescent Chronic Pain: Examining the Role
      of Parents and Peers.
AB  - Objective: The current study focuses on social risk and resilience in an
      adolescent population with chronic pain. Prior research identifies parental
      cognitions and behaviors as influential in youths' experiences of chronic pain
      and pain-related disability. Adolescent development is characterized by greater
      autonomy from parents and an increased emphasis on peer relationships. Study aims
      explore the potential protective effect of high-quality adolescent peer
      relationships on associations between parent and adolescent cognitive and
      behavioral responses to pain. Method: 238 adolescents with mixed-etiology chronic
      pain and their parents completed Pediatric Collaborative Health Outcomes
      Information Registry (Peds-CHOIR) electronic questionnaires prior to their
      initial visit to a tertiary pediatric pain clinic. Variables in this study
      include parent catastrophizing, parent protective behavior, adolescent peer
      relationship quality, adolescent catastrophizing, adolescent functional
      impairment, and demographic and pain characteristics. Results: As expected,
      associations between parent and adolescent cognitive and behavioral pain
      responses were moderated by peer relationship quality. Contrary to expectations,
      for adolescents endorsing low-quality peer relationships, maladaptive adolescent
      outcomes were elevated across levels of parental cognitions and behaviors. For
      adolescents endorsing high-quality peer relationships, adolescent and parent pain
      responses were linearly related. Conclusions: This study highlights the salience
      of both family and peer processes in functional outcomes among adolescents with
      chronic pain. Results suggest that adolescents' adaptive responses to chronic
      pain may be best supported by the simultaneous presence of adaptive parenting and
      high-quality peer relationships. Understanding the larger social context in which
      an adolescent exists is informative in specifying models that predict adaptive
      outcomes or magnify risks.

PMID- 29048555
TI  - An architecture for genomics analysis in a clinical setting using Galaxy and
      Docker.
AB  - Next-generation sequencing is used on a daily basis to perform molecular analysis
      to determine subtypes of disease (e.g., in cancer) and to assist in the selection
      of the optimal treatment. Clinical bioinformatics handles the manipulation of the
      data generated by the sequencer, from the generation to the analysis and
      interpretation. Reproducibility and traceability are crucial issues in a clinical
      setting. We have designed an approach based on Docker container technology and
      Galaxy, the popular bioinformatics analysis support open-source software. Our
      solution simplifies the deployment of a small-size analytical platform and
      simplifies the process for the clinician. From the technical point of view, the
      tools embedded in the platform are isolated and versioned through Docker images.
      Along the Galaxy platform, we also introduce the AnalysisManager, a solution that
      allows single-click analysis for biologists and leverages standardized
      bioinformatics application programming interfaces. We added a Shiny/R interactive
      environment to ease the visualization of the outputs. The platform relies on
      containers and ensures the data traceability by recording analytical actions and
      by associating inputs and outputs of the tools to EDAM ontology through ReGaTe.
      The source code is freely available on Github at
      https://github.com/CARPEM/GalaxyDocker.

PMID- 29048556
TI  - Deep Brain Stimulation-Related Infections: Analysis of Rates, Timing, and
      Seasonality.
AB  - BACKGROUND: Infection is one of the most common complications of deep brain
      stimulation (DBS). Long-term infection rates beyond the immediate postoperative
      period are rarely evaluated. OBJECTIVE: To study short- and long-term DBS-related
      infection rates; to evaluate any potential seasonality associated with DBS
      related infections. METHODS: We retrospectively reviewed all DBS surgeries
      performed in a 5-yr period at 1 hospital by a single surgeon. Infection rates and
      clinical characteristics were analyzed. Postoperative "infections" were defined
      as occurring within 6 mo of implantation of DBS hardware, while "erosions" were
      defined as transcutaneous exposure of hardware at >=6 mo after implantation.
      Based on the date of surgery preceding an infection, rates of infection were
      calculated on a monthly and seasonal basis and compared using Chi square and
      logistic regression analyses. RESULTS: A total of 443 patients underwent 592
      operations; 311 patients underwent primary DBS placement with 632 electrodes.
      Primary DBS placement infection incidence was 2.6%. DBS procedure infection and
      infection rate by electrode were 2.9% and 3.2%, respectively. Infectious
      complications presented later than 6 mo postoperatively in 38% of infected
      patients Summer (July-September) infection rate was significantly higher than
      other seasons (P = .002). The odds ratio of an infection related to a surgery
      performed in August was found to be 4.15 compared to other months (P = .021).
      CONCLUSION: There is a persistent risk of DBS infection and erosion beyond the
      first year of DBS implantation. Start of the academic year was associated with
      increased infection rate at our institution.

PMID- 29048557
TI  - Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution.
AB  - The adenosine-to-inosine (A-to-I) RNA editomes have been systematically
      characterized in various metazoan species, and many editing sites were found in
      clusters. However, it remains unclear whether the clustered editing sites tend to
      be linked in the same RNA molecules or not. By adopting a method originally
      designed to detect linkage disequilibrium of DNA mutations, we examined the
      editomes of ten metazoan species and detected extensive linkage of editing in
      Drosophila and cephalopods. The prevalent linkages of editing in these two
      clades, many of which are conserved between closely related species and might be
      associated with the adaptive proteomic recoding, are maintained by natural
      selection at the cost of genome evolution. Nevertheless, in worms and humans, we
      only detected modest proportions of linked editing events, the majority of which
      were not conserved. Furthermore, the linkage of editing in coding regions of
      worms and humans might be overall deleterious, which drives the evolution of DNA
      sites to escape promiscuous editing. Altogether, our results suggest that the
      linkage landscape of A-to-I editing has evolved during metazoan evolution. This
      present study also suggests that linkage of editing should be considered in
      elucidating the functional consequences of RNA editing.

PMID- 29048558
TI  - Modeling neuro-immune interactions during Zika virus infection.
AB  - Although Zika virus (ZIKV) infection is often asymptomatic, in some cases, it can
      lead to birth defects in newborns or serious neurologic complications in adults.
      However, little is known about the interplay between immune and neural cells that
      could contribute to the ZIKV pathology. To understand the mechanisms at play
      during infection and the antiviral immune response, we focused on neural
      precursor cells (NPCs)-microglia interactions. Our data indicate that human
      microglia infected with the current circulating Brazilian ZIKV induces a similar
      pro-inflammatory response found in ZIKV-infected human tissues. Importantly,
      using our model, we show that microglia interact with ZIKV-infected NPCs and
      further spread the virus. Finally, we show that Sofosbuvir, an FDA-approved drug
      for Hepatitis C, blocked viral infection in NPCs and therefore the transmission
      of the virus from microglia to NPCs. Thus, our model provides a new tool for
      studying neuro-immune interactions and a platform to test new therapeutic drugs.

PMID- 29048559
TI  - Plant phenomics: an overview of image acquisition technologies and image data
      analysis algorithms.
AB  - The study of phenomes or phenomics has been a central part of biology. The field
      of automatic phenotype acquisition technologies based on images has seen an
      important advance in the last years. As with other high-throughput technologies,
      it addresses a common set of problems, including data acquisition and analysis.
      In this review, we give an overview of the main systems developed to acquire
      images. We give an in-depth analysis of image processing with its major issues
      and the algorithms that are being used or emerging as useful to obtain data out
      of images in an automatic fashion.

PMID- 29048560
TI  - Targeting the mesenchymal subtype in glioblastoma and other cancers via
      inhibition of diacylglycerol kinase alpha.
AB  - Background: The mesenchymal phenotype in glioblastoma (GBM) and other cancers
      drives aggressiveness and treatment resistance, leading to therapeutic failure
      and recurrence of disease. Currently, there is no successful treatment option
      available against the mesenchymal phenotype. Methods: We classified patient
      derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and
      other/classical. Each subtype's response to the inhibition of diacylglycerol
      kinase alpha (DGKalpha) was compared both in vitro and in vivo. RhoA activation,
      liposome binding, immunoblot, and kinase assays were utilized to elucidate the
      novel link between DGKalpha and geranylgeranyltransferase I (GGTase I). Results:
      Here we show that inhibition of DGKalpha with a small-molecule inhibitor,
      ritanserin, or RNA interference preferentially targets the mesenchymal subtype of
      GBM. We show that the mesenchymal phenotype creates the sensitivity to DGKalpha
      inhibition; shifting GBM cells from the proneural to the mesenchymal subtype
      increases ritanserin activity, with similar effects in epithelial-mesenchymal
      transition models of lung and pancreatic carcinoma. This enhanced sensitivity of
      mesenchymal cancer cells to ritanserin is through inhibition of GGTase I and
      downstream mediators previously associated with the mesenchymal cancer phenotype,
      including RhoA and nuclear factor-kappaB. DGKalpha inhibition is synergistic with
      both radiation and imatinib, a drug preferentially affecting proneural GBM.
      Conclusions: Our findings demonstrate that a DGKalpha-GGTase I pathway can be
      targeted to combat the treatment-resistant mesenchymal cancer phenotype.
      Combining therapies with greater activity against each GBM subtype may represent
      a viable therapeutic option against GBM.

PMID- 29048561
TI  - A Ca2+-dependent remodelled actin network directs vesicle trafficking to build
      wall ingrowth papillae in transfer cells.
AB  - The transport function of transfer cells is conferred by an enlarged plasma
      membrane area, enriched in nutrient transporters, that is supported on a scaffold
      of wall ingrowth (WI) papillae. Polarized plumes of elevated cytosolic Ca2+
      define loci at which WI papillae form in developing adaxial epidermal transfer
      cells of Vicia faba cotyledons that are induced to trans-differentiate when the
      cotyledons are placed on culture medium. We evaluated the hypothesis that vesicle
      trafficking along a Ca2+-regulated remodelled actin network is the mechanism that
      underpins this outcome. Polarized to the outer periclinal cytoplasm, a Ca2+
      dependent remodelling of long actin bundles into short, thin bundles was found to
      be essential for assembling WI papillae but not the underlying uniform wall
      layer. The remodelled actin network directed polarized vesicle trafficking to
      sites of WI papillae construction, and a pharmacological study indicated that
      both exo- and endocytosis contributed to assembly of the papillae. Potential
      candidates responsible for the Ca2+-dependent actin remodelling, along with those
      underpinning polarized exo- and endocyotosis, were identified in a transcriptome
      RNAseq database generated from the trans-differentiating epidermal cells. Of most
      significance, endocytosis was controlled by up-regulated expression of a dynamin
      like isoform. How a cycle of localized exo- and endocytosis, regulated by Ca2+
      dependent actin remodelling, assembles WI papillae is discussed.

PMID- 29048562
TI  - Fragaria vesca CONSTANS controls photoperiodic flowering and vegetative
      development.
AB  - According to the external coincidence model, photoperiodic flowering occurs when
      CONSTANS (CO) mRNA expression coincides with light in the afternoon of long days
      (LDs), leading to the activation of FLOWERING LOCUS T (FT). CO has evolved in
      Brassicaceae from other Group Ia CO-like (COL) proteins which do not control
      photoperiodic flowering in Arabidopsis. COLs in other species have evolved
      different functions as floral activators or even as repressors. To understand
      photoperiodic development in the perennial rosaceous model species woodland
      strawberry, we functionally characterized FvCO, the only Group Ia COL in its
      genome. We demonstrate that FvCO has a major role in the photoperiodic control of
      flowering and vegetative reproduction through runners. FvCO is needed to generate
      a bimodal rhythm of FvFT1 which encodes a floral activator in the LD accession
      Hawaii-4: a sharp FvCO expression peak at dawn is followed by the FvFT1 morning
      peak in LDs indicating possible direct regulation, but additional factors that
      may include FvGI and FvFKF1 are probably needed to schedule the second FvFT1 peak
      around dusk. These results demonstrate that although FvCO and FvFT1 play major
      roles in photoperiodic development, the CO-based external coincidence around dusk
      is not fully applicable to the woodland strawberry.

PMID- 29048563
TI  - Linear discriminant analysis reveals differences in root architecture in wheat
      seedlings related to nitrogen uptake efficiency.
AB  - Root architecture impacts water and nutrient uptake efficiency. Identifying
      exactly which root architectural properties influence these agronomic traits can
      prove challenging. In this paper, approximately 300 wheat (Triticum aestivum)
      plants were divided into four groups using two binary classifications, high
      versus low nitrogen uptake efficiency (NUpE), and high versus low nitrate in the
      growth medium. The root system architecture for each wheat plant was captured
      using 16 quantitative variables. The multivariate analysis tool, linear
      discriminant analysis, was used to construct composite variables, each a linear
      combination of the original variables, such that the score of the plants on the
      new variables showed the maximum between-group variability. The results show that
      the distribution of root-system architecture traits differs between low- and high
      NUpE plants and, less strongly, between low-NUpE plants grown on low versus high
      nitrate media.

PMID- 29048564
TI  - Phytosiderophores determine thresholds for iron and zinc accumulation in
      biofortified rice endosperm while inhibiting the accumulation of cadmium.
AB  - Nicotianamine (NA) and 2'-deoxymugenic acid (DMA) are metal-chelating ligands
      that promote the accumulation of metals in rice endosperm, but it is unclear how
      these phytosiderophores regulate the levels of different metals and limit their
      accumulation. In this study, transgenic rice plants producing high levels of NA
      and DMA accumulated up to 4-fold more iron (Fe) and 2-fold more zinc (Zn) in the
      endosperm compared with wild-type plants. The distribution of Fe and Zn in
      vegetative tissues suggested that both metals are sequestered as a buffering
      mechanism to avoid overloading the seeds. The buffering mechanism involves the
      modulation of genes encoding metal transporters in the roots and aboveground
      vegetative tissues. As well as accumulating more Fe and Zn, the endosperm of the
      transgenic plants accumulated less cadmium (Cd), suggesting that higher levels of
      Fe and Zn competitively inhibit Cd accumulation. Our data show that although
      there is a strict upper limit for Fe (~22.5 ug g-1 dry weight) and Zn (~84 ug g-1
      dry weight) accumulation in the endosperm, the careful selection of strategies to
      increase endosperm loading with essential minerals can also limit the
      accumulation of toxic metals such as Cd, thus further increasing the nutritional
      value of rice.

PMID- 29048565
TI  - Rice OVATE family protein 6 regulates plant development and confers resistance to
      drought and cold stresses.
AB  - OVATE family proteins (OFPs) regulate multiple aspects of plant growth and
      development; however, their roles in responses to abiotic stresses have not yet
      been studied. Here, we report that rice OsOFP6 regulates growth and development,
      and alters responses to drought and cold stresses. OsOFP6 is expressed in various
      tissues and developmental stages. Knock-down of OsOFP6 by RNA interference (RNAi)
      resulted in semi-dwarf stature, altered grain shape, and shorter lateral roots.
      OsOFP6 was shown to interfere with auxin in regulating lateral root growth and
      initiation, as RNAi plants had increased density of lateral roots under IAA
      (indole-3-acetic acid) treatment. OsOFP6 also affects polar auxin transport,
      which was demonstrated by the different responses of RNAi and OsOFP6
      overexpression (OE) plants to treatment with N-1-naphthylphalamic acid (NPA).
      Furthermore, under drought conditions OE lines showed slower water loss and less
      accumulation of H2O2 compared with RNAi plants, which displayed faster water loss
      and higher H2O2, implying that OsOFP6 may confer both drought avoidance and
      drought tolerance in rice plants. In addition, under cold treatment OE and RNAi
      plants exhibited lower and higher relative electrical conductivity (REC),
      respectively, suggesting an important role of OsOFP6 in response to cold stress.
      These results provide new insights into the multiple functions of OVATE family
      proteins.

PMID- 29048568
TI  - More than just an intermediate: hydrogen sulfide signalling in plants.

PMID- 29048566
TI  - Deciphering the Theobroma cacao self-incompatibility system: from genomics to
      diagnostic markers for self-compatibility.
AB  - Cocoa self-compatibility is an important yield factor and has been described as
      being controlled by a late gameto-sporophytic system expressed only at the level
      of the embryo sac. It results in gametic non-fusion and involves several loci. In
      this work, we identified two loci, located on chromosomes 1 and 4 (CH1 and CH4),
      involved in cocoa self-incompatibility by two different processes. Both loci are
      responsible for gametic selection, but only one (the CH4 locus) is involved in
      the main fruit drop. The CH1 locus acts prior to the gamete fusion step and
      independently of the CH4 locus. Using fine-mapping and genome-wide association
      studies, we focused analyses on restricted regions and identified candidate
      genes. Some of them showed a differential expression between incompatible and
      compatible reactions. Immunolocalization experiments provided evidence of CH1
      candidate genes expressed in ovule and style tissues. Highly polymorphic simple
      sequence repeat (SSR) diagnostic markers were designed in the CH4 region that had
      been identified by fine-mapping. They are characterized by a strong linkage
      disequilibrium with incompatibility alleles, thus allowing the development of
      efficient diagnostic markers predicting self-compatibility and fruit setting
      according to the presence of specific alleles or genotypes. SSR alleles specific
      to self-compatible Amelonado and Criollo varieties were also identified, thus
      allowing screening for self-compatible plants in cocoa populations.

PMID- 29048567
TI  - Green-fruited Solanum habrochaites lacks fruit-specific carotenogenesis due to
      metabolic and structural blocks.
AB  - Members of the tomato clade exhibit a wide diversity in fruit color, but the
      mechanisms governing inter-species diversity of coloration are largely unknown.
      The carotenoid profiles, carotenogenic gene expression and proteome profiles of
      green-fruited Solanum habrochaites (SH), orange-fruited S. galapagense, and red
      fruited S. pimpinellifolium were compared with cultivated tomato [S. lycopersicum
      cv. Ailsa Craig (SL)] to decipher the molecular basis of coloration diversity.
      Green-fruited SH, though it showed normal expression of chromoplast-specific
      phytoene synthase1 and lycopene beta-cyclase genes akin to orange/red-fruited
      species, failed to accumulate lycopene and beta-carotene. The SH phytoene
      synthase1 cDNA encoded an enzymatically active protein, whereas the lycopene beta
      cyclase cDNA was barely active. Consistent with its green-fruited nature, SH's
      fruits retained chloroplast structure and PSII activity, and had impaired
      chlorophyll degradation with high pheophorbide a levels. Comparison of the fruit
      proteomes with SL revealed retention of the proteome complement related to
      photosynthesis in SH. Targeted peptide monitoring revealed a low abundance of key
      carotenogenic and sequestration proteins in SH compared with tomato. The green
      fruitedness of SH appears to stem from blocks at several critical steps
      regulating fruit-specific carotenogenesis namely the absence of chloroplast to
      chromoplast transformation, block in carotenoid biosynthesis, and a dearth of
      carotenoid sequestering proteins.

PMID- 29048569
TI  - Impulse Control in Negative Mood States, Emotional Eating, and Food Addiction are
      Associated with Lower Quality of Life in Adolescents with Severe Obesity.
AB  - Objectives: Quality of life (QoL) is an important outcome to evaluate in
      adolescents with severe obesity, yet intrapersonal predictors of QoL are
      understudied. The current study assessed whether difficulty with impulse control
      when experiencing a negative mood (negative urgency) is associated with poorer
      QoL, mediated by more emotional eating and food addiction. Method: Participants
      consisted of 69 primarily female (71%), minority (76%) adolescents aged 13-21 (M
      age = 16.5, SD = 1.5) with severe obesity presenting for prebariatric surgery
      psychological evaluations. Structural Equation Modeling was used to appraise a
      model of the association of adolescent report of negative urgency with more
      emotional eating (Emotional Eating Scale for Children) and food addiction (Yale
      Food Addiction Scale) and poorer weight-related QoL (Impact of Weight on Quality
      of Life-Kids). Results: Greater difficulty controlling behavior when experiencing
      a negative mood was significantly associated with poorer weight-related QoL, and
      this relationship was mediated by an association with emotional eating and food
      addiction such that adolescents with severe obesity who reported more
      difficulties with impulse control in negative mood states were more likely to
      report more emotional eating and food addiction, which was in turn associated
      with lower QoL. Conclusions: Intrapersonal factors, including impulse control in
      negative mood states, are associated with lower QoL in adolescents with severe
      obesity. Interventions aimed at reducing frequency of negative affect, reducing
      impulsivity in negative mood states, and improving coping skills that are not
      eating based may contribute to improved QoL and merit further study.

PMID- 29048570
TI  - Earlier Pediatric Psychology Consultation Predicts Lower Stem Cell
      Transplantation Hospital Costs.
AB  - Objective: The purpose of this study was to examine the hypothesis that earlier
      time to psychology consultation would predict lower costs for the initial stem
      cell transplant (SCT) hospitalization among patients receiving care at a
      children's hospital. Methods: A retrospective medical record review identified 75
      patients (ages 0-32 years) with one or more visits by a licensed clinical
      psychologist during the initial SCT hospitalization from 2010 to 2014.
      Demographic and clinical variables were obtained from the electronic medical
      record and hospitalization costs were obtained from patient billing records. A
      generalized linear model with a gamma distribution and log link function was used
      to estimate the relationship between time to psychology consultation and cost for
      the initial SCT hospitalization while controlling for demographic, clinical, and
      utilization factors. Results: After controlling for age at SCT, gender, race,
      insurance status, diagnosis, SCT type, length of stay, and number of psychology
      visits, earlier time to psychology consultation predicted lower costs for the
      initial SCT hospitalization (chi2 = 6.83, p = .01). When the effects of
      covariates were held constant, every day increase in the time to psychology
      consultation was associated with a 0.3% increase in SCT hospitalization costs
      (beta = 0.003, SE = 0.001). Conclusions: Results suggest that facilitating
      consultations with a pediatric psychologist early in the initial SCT
      hospitalization may reduce costs for patients undergoing SCT at children's
      hospitals. Future research is needed to determine the optimal timing of
      psychology consultation and quantify the economic impact of psychological
      services.

PMID- 29048571
TI  - Topical Review: Pain in Survivors of Pediatric Cancer: Applying a Prevention
      Framework.
AB  - Objective: To apply a biopsychosocial framework to understand factors influencing
      pain in survivors of pediatric cancer to inform pain prevention efforts and
      highlight the need for interdisciplinary care. Method: This topical review draws
      from both pediatric cancer survivorship research and chronic noncancer pain
      research to illustrate how components of a preventative model can be applied to
      pain in survivorship. Results: Pain is a common experience among long-term
      survivors of pediatric cancer. The pain experience in survivorship can be
      conceptualized in terms of biological disease and treatment factors, cognitive
      and affective factors, and social and contextual factors. We review literature
      pertinent to each of these biopsychosocial factors and tailor an existing public
      health prevention framework for pain in survivors of pediatric cancer.
      Conclusions: Classifying survivors of pediatric cancer into pain risk categories
      based on their daily experiences of pain, pain-related functional impairment, and
      distress could help guide the implementation of pain-related prevention and
      intervention strategies in this population. Future research is needed to
      establish the efficacy of screening measures to identify patients in need of
      psychosocial pain and pain-related fear management services, and
      interdisciplinary pediatric chronic pain management programs in survivors of
      pediatric cancer.

PMID- 29048572
TI  - Ventriculoscopic Surgery for Cystic Retrochiasmatic Craniopharyngiomas:
      Indications, Surgical Technique, and Short-Term Patient Outcomes.
AB  - BACKGROUND: Attempted gross-total resection for the management of cystic
      retrochiasmatic craniopharyngiomas can cause severe hypothalamic dysfunction and
      decrease overall survival. Ventriculoscopic surgery is a minimally invasive
      alternative; however, potential indications and technique have not been well
      defined. OBJECTIVE: To present our indications and technique for the
      ventriculoscopic treatment of cystic retrochiasmatic craniopharyngiomas. METHODS:
      We evaluated all patients with retrochiasmatic craniopharyngiomas for
      ventriculoscopic surgery. Indications and operative technique were developed to
      minimize operative morbidity, relieve mass effect, and optimize functional
      outcome. Cyst size and functional outcomes were statistically evaluated to
      determine radiographic and short-term clinical outcome. RESULTS: Indications for
      ventriculoscopic surgery included (1) radiographic evidence of hypothalamic
      involvement and (2) major cystic component. Ten patients met indications, and
      mean follow-up was 2.5 +/- 1.6 yr. The surgical technique included wide cyst
      fenestration at the foramen of Monro, and fenestration of inferior cyst
      wall/third ventriculostomy ("through-and-through" technique). Preoperative
      Karnofsky performance status was 70 +/- 15 and was inversely correlated with
      preoperative cyst size (13 +/- 13 cm3). A statistically significant reduction in
      cyst size was found on early postoperative imaging (2.1 +/- 4.3 cm3). Seven
      patients received postoperative radiotherapy. Postoperative performance scores
      (81 +/- 8.3) had improved; no patient suffered functional decline. Pre- and
      postoperative body mass indices were similar. No patient had short-term
      hypothalamic obesity. CONCLUSION: Ventriculoscopic surgery, with or without
      adjuvant treatments, can reduce early postoperative tumor volume and improve
      short-term functional status in cystic retrochiasmatic craniopharyngiomas with
      hypothalamic involvement; it should be considered a minimally invasive option in
      the multimodal treatment of craniopharyngiomas. Further studies are needed to
      determine long-term efficacy.

PMID- 29048574
TI  - Featured Article: Community Crime Exposure and Risk for Obesity in Preschool
      Children: Moderation by the Hypothalamic-Pituitary-Adrenal-Axis Response.
AB  - Objective: Identification of early risk factors related to obesity is critical to
      preventative public health efforts. In this study, we investigated links between
      the Hypothalamic-Pituitary-Adrenal (HPA)-axis activity (diurnal cortisol
      pattern), geospatially operationalized exposure to neighborhood crime, and body
      mass index (BMI) for a sample of 5-year-old children. Greater community crime
      exposure and lower HPA-axis activity were hypothesized to contribute to higher
      BMI, with child HPA-axis moderating the association between crime exposure and
      BMI. Method: Families residing within the boundaries of the City of Seattle (N =
      114) provided information concerning demographic/psychosocial risk factors, used
      to calculate a Cumulative Risk Index, indicating the number of contextual
      adversities present. Child BMI and diurnal cortisol pattern (derived from assays
      of saliva samples) were examined, along with neighborhood crime indices computed
      with publically available information, based on participants' locations. Results:
      Hierarchical multiple regression analyses, adjusted for covariates (cumulative
      risk, age, and sex), indicated that crime proximity made a unique contribution to
      child BMI, in the direction signaling an increase in the risk for obesity.
      Consistent with our hypothesis, a significant interaction was observed,
      indicative of moderation by diurnal cortisol pattern. Follow-up simple slope
      analyses demonstrated that crime exposure was significantly related to higher BMI
      for children with low-flat (blunted) diurnal cortisol patterns, where community
      crime and BMI were not significantly associated at higher levels of cortisol.
      Conclusion: Community crime exposure contributes to higher BMI as early as the
      preschool period, and blunted diurnal cortisol patterns may place children
      experiencing neighborhood adversity at greater risk for obesity.

PMID- 29048573
TI  - The Rate of Evolution of Postmating-Prezygotic Reproductive Isolation in
      Drosophila.
AB  - Reproductive isolation is an intrinsic aspect of species formation. For that
      reason, the identification of the precise isolating traits, and the rates at
      which they evolve, is crucial to understanding how species originate and persist.
      Previous work has measured the rates of evolution of prezygotic and postzygotic
      barriers to gene flow, yet no systematic analysis has studied the rates of
      evolution of postmating-prezygotic (PMPZ) barriers. We measured the magnitude of
      two barriers to gene flow that act after mating occurs but before fertilization.
      We also measured the magnitude of a premating barrier (female mating rate in
      nonchoice experiments) and two postzygotic barriers (hybrid inviability and
      hybrid sterility) for all pairwise crosses of all nine known extant species
      within the melanogaster subgroup. Our results indicate that PMPZ isolation
      evolves faster than hybrid inviability but slower than premating isolation. Next,
      we partition postzygotic isolation into different components and find that, as
      expected, hybrid sterility evolves faster than hybrid inviability. These results
      lend support for the hypothesis that, in Drosophila, reproductive isolation
      mechanisms (RIMs) that act early in reproduction (or in development) tend to
      evolve faster than those that act later in the reproductive cycle. Finally, we
      tested whether there was evidence for reinforcing selection at any RIM. We found
      no evidence for generalized evolution of reproductive isolation via reinforcement
      which indicates that there is no pervasive evidence of this evolutionary process.
      Our results indicate that PMPZ RIMs might have important evolutionary
      consequences in initiating speciation and in the persistence of new species.

PMID- 29048576
TI  - Monitoring characteristics and genotoxic effects of engineered nanoparticle
      protein corona.
AB  - Engineered nanoparticles (ENPs) possess different physical and chemical
      properties compared to their bulk counterparts. These unique properties have
      found application in various products in the area of therapeutics, consumer
      goods, environmental remediation, optical and electronic fields. This has also
      increased the likelihood of their release into the environment thereby affecting
      human health and ecosystem. ENPs, when in contact with the biological system have
      various physical and chemical interactions with cellular macromolecules including
      proteins. These interactions lead to the formation of protein corona around the
      ENPs. Consequently, living systems interact with the protein-coated ENP rather
      than with a bare ENP. This ENP-protein interaction influences uptake,
      accumulation, distribution and clearance and thereby affecting the cytotoxic and
      genotoxic responses. Although there are few studies which discussed the fate of
      ENPs, there is a need for extensive research in the field of ENPs, to understand
      the interaction of ENPs with biological systems for their safe and productive
      application.

PMID- 29048577
TI  - Commentary: Overlapping Surgeries Are Not Associated With Worse Patient Outcomes:
      Retrospective Multivariate Analysis of 14 872 Neurosurgical Cases Performed at a
      Single Institution.

PMID- 29048575
TI  - MicroRNA-binding site polymorphisms in genes involved in colorectal cancer
      etiopathogenesis and their impact on disease prognosis.
AB  - According to the Vogelstein's model of colorectal carcinogenesis, genetic
      variations in highly penetrant genes may be involved in the colorectal cancer
      (CRC) pathogenesis. Similarly, aberrant function and/or altered expression of
      microRNAs (miRNAs) often occur in CRC. In this context, polymorphisms in miRNA
      binding sites (miRSNPs) may affect miRNA/target gene interaction, resulting in
      differential mRNA/protein expression and increased susceptibility to common
      diseases. To explore this phenomenon, we have mined the 3' untranslated regions
      (3'UTRs) of genes known to be frequently mutated in CRC to search for miRSNPs and
      tested their association with CRC risk and clinical outcome. Eight miRSNPs
      (rs1804191, rs397768, rs41116 in APC; rs1137918, s227091, rs4585 in ATM; rs712,
      rs1137282, rs61764370 in KRAS; rs8674 in PARP1 and rs16950113 in SMAD7) were
      tested for their association with CRC risk in a case-control study (1111 cases
      and 1469 healthy controls). The role of these miRSNPs was also investigated in
      relation to clinical outcome on a subset of patients with complete follow-up.
      rs8679 within PARP1 was associated with CRC risk and patients' survival. In the
      dominant model, carriers of at least one C allele were at a decreased risk of
      cancer (P = 0.05). The CC genotype in rs8679 was also associated with an
      increased risk of recurrence/progression in patients that received 5-FU-based
      chemotherapy (log-rank test P = 0.03). Carriers of the homozygous variant
      genotype TT for rs712 in KRAS gene were associated with a decreased risk of
      rectal cancer (odds ratio (OR) = 0.65, 95% confidence intervals (CI) 0.43-1.00, P
      = 0.05) while individuals with colon cancer carrying the heterozygous GT genotype
      showed a longer overall survival (OS) (P = 0.04). We provide the first evidence
      that variations in potential miRNA-binding target sites in the 3' UTR of PARP1
      gene may modulate CRC risk and prognosis after therapy. Further studies are
      needed to replicate our finding and assess miRSNPs as predictive biomarkers in
      independent populations.

PMID- 29048579
TI  - Development of high-grade osteosarcoma in a patient with recurrent giant cell
      tumor of the ischium while receiving treatment with denosumab.
AB  - Malignant transformation of giant cell tumor of bone (GCTB) without radiotherapy
      exposure is exceptionally rare, occurring in less than 1% of GCTBs. The safety
      and efficacy of denosumab in patients with GCTB was recently reported. We herein
      report a case of a benign recurrent GCTB with an H3F3A mutation that underwent
      secondary malignant transformation during treatment with denosumab. A 29-year-old
      woman underwent curettage of a GCTB of the left ischium in 2005. Ten years after
      the first surgery, the GCTB recurred locally. We started treatment with
      denosumab. During the first 5 months of treatment, we observed a demarcated area
      of osteosclerosis in the recurrent lesion, and the patient's clinical condition
      improved. At 6 months, however, the patient developed pain, and a rapidly growing
      mass was detected by computed tomography. An incisional biopsy was performed.
      Histologic analysis showed a high-grade osteosarcoma. The patient developed lung
      metastases and died soon after beginning chemotherapy. The mechanism of
      sarcomatous transformation of GCTB during denosumab therapy is unclear. These
      findings suggest that the scientific community should be aware of the possible
      malignant transformation of GCTB during denosumab treatment.

PMID- 29048578
TI  - Genome assembly and transcriptome resource for river buffalo, Bubalus bubalis (2n
      = 50).
AB  - Water buffalo is a globally important species for agriculture and local
      economies. A de novo assembled, well-annotated reference sequence for the water
      buffalo is an important prerequisite for studying the biology of this species,
      and is necessary to manage genetic diversity and to use modern breeding and
      genomic selection techniques. However, no such genome assembly has been
      previously reported. There are 2 species of domestic water buffalo, the river (2
      n = 50) and the swamp (2 n = 48) buffalo. Here we describe a draft quality
      reference sequence for the river buffalo created from Illumina GA and Roche 454
      short read sequences using the MaSuRCA assembler. The assembled sequence is 2.83
      Gb, consisting of 366 983 scaffolds with a scaffold N50 of 1.41 Mb and contig N50
      of 21 398 bp. Annotation of the genome was supported by transcriptome data from
      30 tissues and identified 21 711 predicted protein coding genes. Searches for
      complete mammalian BUSCO gene groups found 98.6% of curated single copy orthologs
      present among predicted genes, which suggests a high level of completeness of the
      genome. The annotated sequence is available from NCBI at accession
      GCA_000471725.1.

PMID- 29048580
TI  - The impact of young age on the prognosis for colorectal cancer: a population
      based study in Taiwan.
AB  - Background: The impact of age as a prognostic factor for patients with colorectal
      cancer (CRC) remains controversial, possibly due to heterogeneity between studies
      in terms of patient numbers, percentage of patients undergoing curative
      resection, percentage of patients receiving neoadjuvant therapy, or failure to
      adjust for potential confounding factors. This study used colorectal cancer
      survival data from the Taiwan Cancer Registry database in order to
      comprehensively analyze age as a prognostic factor. Methods: Survival data were
      analyzed for 62 060 CRC patients diagnosed with adenocarcinoma, mucinous
      adenocarcinoma, or signet-ring cell carcinoma of the colon and rectum between
      1998 and 2005. The rates of all-cause mortality and CRC-related mortality were
      determined using Kaplan-Meier analysis, and the log-rank test was used to compare
      differences in survival between different age groups. The crude and adjusted
      hazard ratios for all-cause and CRC-related mortalities were calculated according
      to the estimates from the univariable and multivariable Cox proportional hazard
      models. Results: Patients in the <=40 and the 41-50 age groups had a higher
      proportion of mucinous adenocarcinoma (P < 0.001) and signet-ring cell carcinoma
      (P < 0.001) compared to the older age groups. After adjusting for gender,
      histology, and tumor site, patients in the <=40 age group had a poorer overall
      survival (OS) and cancer-specific survival compared to patients in the 41-50 and
      51-60, and 61-70 age groups (P < 0.001), but a better OS and cancer-specific
      survival compared to patients in the 71-80 and >80 age groups (P < 0.001).
      Conclusions: Our study indicated that age is an important consideration while
      determining the clinical management of CRC patients.

PMID- 29048581
TI  - The estimates of 5-year uterus cancer prevalence in adult population in 2012.

PMID- 29048583
TI  - Comparative Efficacy of Commercial Mosquito Coils Against Aedes aegypti (Diptera:
      Culicidae) in Malaysia: A Nationwide Report.
AB  - This study was conducted using the glass chamber method to determine the
      susceptibility status of the dengue vector, Aedes aegypti (L.) from 11 states in
      Malaysia to commercial mosquito coils containing four different active
      ingredients, namely metofluthrin, d-allethrin, d-trans allethrin, and
      prallethrin. Aedes aegypti exhibited various knockdown rates, ranging from 14.44%
      to 100.00%, 0.00% to 61.67%, 0.00% to 90.00%, and 0.00% to 13.33% for
      metofluthrin, d-allethrin, d-trans allethrin, and prallethrin, respectively.
      Overall, mortality rates ranging from 0.00% to 78.33% were also observed among
      all populations. Additionally, significant associations were detected between the
      knockdown rates of metofluthrin and d-allethrin, and between metofluthrin and d
      trans allethrin, suggesting the occurrence of cross-resistance within pyrethroid
      insecticides. Overall, this study revealed low insecticidal activity of mosquito
      coils against Ae. aegypti populations in Malaysia, and consequently may provide
      minimal personal protection against mosquito bites.

PMID- 29048582
TI  - Salience network dynamics underlying successful resistance of temptation.
AB  - Self-control and the ability to resist temptation are critical for successful
      completion of long-term goals. Contemporary models in cognitive neuroscience
      emphasize the primary role of prefrontal cognitive control networks in aligning
      behavior with such goals. Here, we use gaze pattern analysis and dynamic
      functional connectivity fMRI data to explore how individual differences in the
      ability to resist temptation are related to intrinsic brain dynamics of the
      cognitive control and salience networks. Behaviorally, individuals exhibit
      greater gaze distance from target location (e.g. higher distractibility) during
      presentation of tempting erotic images compared with neutral images. Individuals
      whose intrinsic dynamic functional connectivity patterns gravitate toward
      configurations in which salience detection systems are less strongly coupled with
      visual systems resist tempting distractors more effectively. The ability to
      resist tempting distractors was not significantly related to intrinsic dynamics
      of the cognitive control network. These results suggest that susceptibility to
      temptation is governed in part by individual differences in salience network
      dynamics and provide novel evidence for involvement of brain systems outside
      canonical cognitive control networks in contributing to individual differences in
      self-control.

PMID- 29048584
TI  - Effect of Body Size, Age, and Premating Experience on Male Mating Success in
      Bactrocera tryoni (Diptera: Tephritidae).
AB  - Variation in male body size, age, and prior sexual experience may all influence
      male mating success in tephritid fruit flies. Bactrocera tryoni (Froggatt) is an
      Australian pest tephritid for which the sterile insect technique (SIT) is being
      actively pursued, and for which information on what makes males more competitive
      is urgently needed. Pair-wise competitive mating trials were run using laboratory
      reared flies in walk-in field cages, evaluating young, large, and virgin B.
      tryoni males against old, small, and nonvirgin males, respectively. Analysis of
      male sexual competitiveness indices revealed that young and large males obtained
      significantly more copulations compared to old and small males; there was no
      significant difference between virgin and nonvirgin males in obtaining mates.
      While SIT programs will always release young males, the results do show that
      rearing programs which focus on producing larger males, rather than greater
      numbers of smaller males, will produce more sexually competitive males. After
      release, virgin SIT males will not be at a competitive disadvantage with sexually
      experienced males based on prior mating experience.

PMID- 29048585
TI  - Mowing Height Influences Listronotus maculicollis (Coleoptera: Curculionidae)
      Oviposition Behavior and Mechanical Removal From Golf Course Putting Greens, but
      Not Larval Development.
AB  - The annual bluegrass weevil, Listronotus maculicollis (Kirby), is a highly
      destructive pest of golf course turfgrass in eastern North America. Previous
      research has demonstrated that females prefer to oviposit within short-mown
      turfgrasses (<1.25 cm), and these offspring have improved fitness traits compared
      with larvae developing in higher-mowed turf. However, damage to putting green
      turf (<3.55 mm) is rarely reported. We investigated whether this phenomenon was
      due to adult removal through mowing or an inability of larvae to develop within a
      shortened plant. Greenhouse studies revealed that between 26% and 38% of adults
      were removed when turf was mowed at 2.54 mm (0.100 in), but the effect diminished
      with increasing mowing heights. The majority of adults survived mowing,
      indicating a potential for adults to reinvade turf stands adjacent to areas where
      grass clippings are discarded. Females oviposited in all mowing height treatments
      in laboratory and field experiments. However, behavior was influenced by plant
      height, as significantly fewer eggs were placed inside of the turfgrass stem at
      the lowest mowing height. Larval development was not affected by egg placement or
      turf height, and significant numbers of larvae were capable of developing to
      damaging stages (fourth- and fifth-instar larvae) in all treatments. Our findings
      suggest that L. maculicollis poses a threat to putting green-height turf, but the
      probability of damage occurring and need for insecticide applications may be
      lessened on low-mown surfaces. Future studies are needed to determine factors
      that influence L. maculicollis movement within the turfgrass canopy to optimize
      mechanical control.

PMID- 29048586
TI  - Nitric Oxide Fumigation for Control of Bulb Mites on Flower Bulbs.
AB  - In this article, the efficacy of nitric oxide (NO) fumigation to control bulb
      mites in the genus Rhizoglyphus and its effects on germination and growth of
      flower bulbs were studied. Bulb mites on infested peanuts were fumigated with NO
      at different concentrations under ultralow oxygen conditions in 1.9-liter jars
      for 4-48 h at various temperatures ranging from 2 to 20  degrees C. Bulb mites
      were susceptible to NO fumigation treatment. Efficacy of fumigation treatment
      increased with increased concentration, treatment time, and temperature within
      the ranges tested. Complete control of bulb mites was achieved in 24-h fumigation
      with 3.0% and 5.0% NO at 10  degrees C and with 2.0% NO at 20  degrees C. A
      fumigation treatment with 3.0% NO at 20  degrees C for 24 h, which was stronger
      than necessary for bulb mite control, was tested on bulbs of four flower
      varieties to determine its safety on germination and growth of the flower bulbs.
      The NO fumigation treatments did not significantly affect germination and growth
      of flower bulbs. This study showed that NO fumigation was effective against bulb
      mites on peanuts and did not affect germination and growth of flower bulbs.
      Therefore, NO fumigation has potential for postharvest control of bulb mites on
      flower bulbs.

PMID- 29048588
TI  - Bertiella studeri Infection-A Rare Cause of Chronic Abdominal Pain in a Child
      from North India.
AB  - Bertiella is a common parasite seen in non-human primates. It is rarely seen in
      humans. We present the case of a 2-year-old child with bertiellosis. He had
      recurrent abdominal pain, and worm fragments were found in stool, which were
      refractory to albendazole therapy.

PMID- 29048587
TI  - Xylosandrus germanus (Coleoptera: Curculionidae: Scolytinae) Occurrence, Fungal
      Associations, and Management Trials in New York Apple Orchards.
AB  - Xylosandrus germanus (Blandford) has caused increasing damage in high-density New
      York apple orchards since 2013, resulting in tree decline and death. We
      documented their occurrence and timing in > 50 orchards using ethanol-baited
      traps from 2014 to 2016. First captures ranged from 48 to 83 degree days (base 10
      degrees C) from 1 January. Captures were numerically higher at the orchard-woods
      interface than within the orchard interior, but differences were not significant
      in locations with lower populations. Control using insecticide trunk sprays was
      tested in potted, waterlogged apple trees placed in orchards and nurseries, and
      inside wooded areas adjacent to orchards. A verbenone repellent was used in
      combination with trunk sprays to improve control. Overall, insecticide sprays
      were inconsistent and marginal in preventing new infestations. Chlorpyrifos
      significantly reduced infestations versus lambda-cyhalothrin and untreated trees
      at one location in the 2015 orchard trials, and versus untreated trees at one
      location in the 2016 nursery trials, but otherwise performed no better than other
      treatments. The addition of verbenone to either the check or permethrin
      treatments resulted in significantly fewer attack sites containing brood at one
      orchard site in 2016. Chlorpyrifos, lambda-cyhalothrin, and permethrin
      significantly reduced the number of attack sites containing adults compared with
      untreated trees at one nursery trial location in 2016, but were otherwise
      ineffective in reducing numbers of trees in other locations and infestation
      categories. We found several fungal and bacterial species associated with X.
      germanus and its infestation of apples. These microbes likely play a minimal role
      in apple decline.

PMID- 29048589
TI  - Impact of Trajectory Planning With Susceptibility-Weighted Imaging for
      Intracranial Electrode Implantation.
AB  - BACKGROUND: While T1-weighted gadolinium-enhanced (T1-Gd) magnetic resonance
      imaging (MRI) is the standard imaging sequence for trajectory planning of
      stereotactic procedures, including deep brain stimulation,
      stereoelectroencephalography, and laser interstitial thermal therapy,
      susceptibility-weighted imaging (SWI) has been reported to demonstrate increased
      sensitivity for the visualization of microvasculature. OBJECTIVE: To determine
      the impact of SWI visualization on trajectory planning for electrode implantation
      and evaluate the relationship between the rate of vessel-electrode intersections
      and intracerebral hemorrhage (ICH). METHODS: We conducted a retrospective study
      of 13 patients who underwent stereoelectroencephalography and laser interstitial
      thermal therapy placement between 2014 and 2015, using their preoperative T1-Gd
      and SWI scans, and postoperative MRI scans to determine the rate of vessel
      electrode intersections seen on the 2 imaging modalities, the mean diameter and
      depth of the vessels identified, and the rate of ICH after implantation. RESULTS:
      Among 13 patients, 106 electrodes were implanted. Sixty-three unique vessel
      electrode intersections were identified on SWI with a mean of 4.85 intersections
      per patient. There were 13 intersections seen on T1-Gd with a mean of 1
      intersection per patient. The intersected vessels visualized on SWI had a
      diameter of 1.49 +/- 0.46 mm and those on T1-Gd were 2.01 +/- 0.52 mm. There was
      no clear ICH observed in this series. CONCLUSION: SWI allows for improved
      visualization of the smaller, deep vessels, whereas T1-Gd adequately detects
      superficial, larger vessels. Despite the larger number of vessel-electrode
      intersections seen on SWI, no clear evidence of ICH was identified. Increased
      detection of deep vasculature does not appear to significantly benefit trajectory
      planning for stereotactic intracranial procedures and may limit the number of
      trajectories perceived to be safe.

PMID- 29048590
TI  - Family Functioning, Medical Self-Management, and Health Outcomes Among School
      Aged Children With Sickle Cell Disease: A Mediation Model.
AB  - Background: Informed by the Pediatric Self-Management Model, the present study
      tested relationships between parent and family functioning, sickle cell disease
      (SCD) self-management, and health outcomes for children with SCD. Method: 83
      children with SCD and a parent completed baseline data as part of a larger
      investigation of a family-based, problem-solving intervention for children with
      SCD (M age = 8.47). Youth and parents completed a measure of child health-related
      quality of life (HRQOL), and parents completed measures of family efficacy,
      parenting stress, and SCD self-management. SCD pain episodes and urgent health
      utilization information over the past year were obtained via medical chart
      review. Results: SCD self-management mediated the relationship between parent
      reported family efficacy and parent proxy HRQOL, as well as the relationship
      between parenting stress and child and parent proxy HRQOL. Mediation models were
      nonsignificant for outcomes beyond HRQOL, including SCD pain episodes and urgent
      health utilization. Conclusion: Fostering family efficacy and reducing parenting
      stress may be meaningful intervention targets for improving SCD self-management
      and child HRQOL among school-aged children. Although findings were consistent
      with the Pediatric Self-Management Model in terms of HRQOL, the model was not
      supported for pain episodes or urgent health utilization, highlighting the need
      for multi-method, longitudinal research on the SCD self-management behaviors that
      are linked to preventable health outcomes.

PMID- 29048591
TI  - The Impact of a Pediatric Shunt Surgery Checklist on Infection Rate at a Single
      Institution.
AB  - BACKGROUND: Shunt infections remain a significant challenge in pediatric
      neurosurgery. Numerous surgical checklists have been introduced to reduce
      infection rates. OBJECTIVE: To introduce an evidence-based shunt surgery
      checklist and its impact on our shunt infection rate. METHODS: Between January 1,
      2008 and December 31, 2015, pediatric patients who underwent shunt surgery at our
      institution were indexed in a prospectively maintained database. All definitive
      shunt procedures were included. Shunt infection was defined according to the
      Center for Disease Control and Prevention's National Hospital Safety Network
      surveillance definition for surgical site infection. Clinical and procedural
      variables were abstracted per procedure. Infection data were compared for the 4
      year before and 4 year after protocol implementation. Compliance was calculated
      from retrospective review of our checklists. RESULTS: Over the 8-year study
      period, 1813 procedures met inclusion criteria with a total of 37 shunt
      infections (2%). Prechecklist (2008-2011) infection rate was 3.03% (28/924) and
      decreased to 1.01% (9/889; P = .003) postchecklist (2012-2015), representing an
      absolute risk reduction of 2.02% and relative risk reduction of 66.6%. One shunt
      infection was prevented for every 50 times the checklist was used. Those patients
      who developed an infection after protocol implementation were younger (0.95 years
      vs 3.40 years (P = .027)), but there were no other clinical or procedural
      variables, including time to infection, that were significantly different between
      the cohorts. Average compliance rate among required checklist components was 97%
      (range 85%-100%). CONCLUSION: Shunt surgery checklist implementation correlated
      with lower infection rates that persisted in the 4 years after implementation.

PMID- 29048592
TI  - The yeast 2-MUm plasmid Raf protein contributes to plasmid inheritance by
      stabilizing the Rep1 and Rep2 partitioning proteins.
AB  - The yeast 2-MUm plasmid is a remarkable genetic parasite, managing efficient
      maintenance at high-copy number with minimal impact on the host. Equal
      partitioning of the plasmid upon host cell division requires plasmid proteins
      Rep1 and Rep2 and the plasmid STB locus. The Rep proteins and the plasmid-encoded
      Raf protein also regulate plasmid gene transcription. In this study, protein
      interaction assays, sequence analyses and mutational approaches were used to
      identify domains and residues in Rep2 and Raf required for association with Rep1
      and Rep2 and to delineate the Rep2 DNA-binding domain. Rep2 and Raf displayed
      similarities in interactions with Rep1 and Rep2, in having Rep1 promote their STB
      association in vivo, and in stabilizing Rep protein levels. Rep2 mutants impaired
      for self-association were competent for transcriptional repression while those
      deficient for Rep1 association were not. Surprisingly, Rep2 mutants impaired for
      either Rep1 interaction or self-association were able to maintain efficient
      plasmid inheritance provided Raf was present and competent for Rep protein
      interaction. Our findings provide insight into the Rep protein complexes required
      for partitioning and transcriptional repression, and suggest that in addition to
      its transcriptional function, Raf stabilization of Rep partitioning proteins
      contributes to the remarkable persistence of the 2-MUm plasmid.

PMID- 29048593
TI  - Fidelity of RNA templated end-joining by chlorella virus DNA ligase and a novel
      iLock assay with improved direct RNA detection accuracy.
AB  - Ligation-based nucleic acid detection methods are primarily limited to DNA, since
      they exhibit poor performance on RNA. This is attributed to reduced end-joining
      efficiency and/or fidelity of ligases. Interestingly, chlorella virus DNA ligase
      (PBCV-1 DNA ligase) has recently been shown to possess high RNA-templated DNA end
      joining activity; however, its fidelity has not yet been systematically
      evaluated. Herein, we characterized PBCV-1 ligase for its RNA-templated end
      joining fidelity at single base mismatches in 3' and 5' DNA probe termini and
      found an overall limited end-joining fidelity. To improve the specificity in PBCV
      1 ligase-driven RNA detection assays, we utilized structure-specific 5'
      exonucleolytic activity of Thermus aquaticus DNA polymerase, used in the invader
      assay. In the iLock (invader padLock) probe assay, padlock probe molecules are
      activated prior ligation thus the base at the probe ligation junction is read
      twice in order to aid successful DNA ligation: first, during structure-specific
      invader cleavage and then during sequence-specific DNA ligation. We report two
      distinct iLock probe activation mechanisms and systematically evaluate the assay
      specificity, including single nucleotide polymorphisms on RNA, mRNA and miRNA. We
      show significant increase in PBCV-1 ligation fidelity in the iLock probe assay
      configuration for RNA detection.

PMID- 29048595
TI  - Ultraviolet radiation and skin cancer risk in offshore workers.
AB  - Background: Excess skin cancer mortality and incidence have been reported among
      both land-based and offshore petroleum workers. The association between skin
      cancer and ultraviolet radiation (UVR) exposure has not been examined in these
      workers, although they have long off-duty periods and high average income that
      may allow travelling to sunny destinations. In addition, they have access to
      solariums free of charge on many accommodation platforms. Aims: To prospectively
      examine risk of incident cutaneous melanoma (CM) and non-melanoma skin cancer
      (NMSC), according to sun-tanning habits with adjustment for aromatic hydrocarbon
      exposure. Methods: A cohort of men employed offshore from 1965 to 1999 was linked
      through the Cancer Registry of Norway 1999-2012. Cox regression adapted to a
      stratified case-cohort design was used to estimate hazard ratios with 95%
      confidence intervals. Results: The cohort included 24917 men. During 13.5 years
      of follow-up, 112 CMs and 70 NMSCs occurred. A positive dose-response
      relationship was seen between sunburn frequency and risk of CM (Ptrend < 0.05)
      and NMSC (Ptrend < 0.01). Solarium use both before and after age 20 was related
      to increased risk of NMSC. Sunscreen use was associated with increased risk of
      NMSC (Ptrend < 0.001). Conclusions: UVR exposure seems to be a significant
      contributor to the elevated risk of skin cancer observed in North Sea offshore
      workers. The positive association between solarium use and NMSC risk adds to the
      growing body of literature on artificial UV devices as carcinogenic.

PMID- 29048594
TI  - Neptune: a bioinformatics tool for rapid discovery of genomic variation in
      bacterial populations.
AB  - The ready availability of vast amounts of genomic sequence data has created the
      need to rethink comparative genomics algorithms using 'big data' approaches.
      Neptune is an efficient system for rapidly locating differentially abundant
      genomic content in bacterial populations using an exact k-mer matching strategy,
      while accommodating k-mer mismatches. Neptune's loci discovery process identifies
      sequences that are sufficiently common to a group of target sequences and
      sufficiently absent from non-targets using probabilistic models. Neptune uses
      parallel computing to efficiently identify and extract these loci from draft
      genome assemblies without requiring multiple sequence alignments or other
      computationally expensive comparative sequence analyses. Tests on simulated and
      real datasets showed that Neptune rapidly identifies regions that are both
      sensitive and specific. We demonstrate that this system can identify trait
      specific loci from different bacterial lineages. Neptune is broadly applicable
      for comparative bacterial analyses, yet will particularly benefit pathogenomic
      applications, owing to efficient and sensitive discovery of differentially
      abundant genomic loci. The software is available for download at:
      http://github.com/phac-nml/neptune.

PMID- 29048596
TI  - Cochrane Work-championing facts since 2003.

PMID- 29048597
TI  - The Holmes-Rahe Stress Inventory.

PMID- 29048598
TI  - Pregnancy outcomes in partners of male divers.

PMID- 29048599
TI  - Occupational medicine: paradise lost.

PMID- 29048600
TI  - Earning CPD points.

PMID- 29048601
TI  - Screening for Natural Variation in Water Use Efficiency Traits in a Diversity Set
      of Brassica napus L. Identifies Candidate Variants in Photosynthetic
      Assimilation.
AB  - Seed yield and quality of crop species are significantly reduced by water
      deficit. Stable isotope screening (delta13C) of a diversity set of 147 accessions
      of Brassica napus grown in the field identified several accessions with extremes
      in water use efficiency (WUE). We next conducted an investigation of the
      physiological characteristics of selected natural variants with high and low WUE
      to understand how these characteristics translate to differences in WUE. We
      identified an interesting Spring accession, G302 (Mozart), that exhibited the
      highest WUE in the field and high CO2 assimilation rates coupled with an
      increased electron transport capacity (Jmax) under the imposed conditions.
      Differences in stomatal density and stomatal index did not translate to
      differences in stomatal conductance in the investigated accessions. Stomatal
      conductance response to exogenous ABA was analyzed in selected high and low WUE
      accessions. Spring lines showed little variation in response to exogenous ABA,
      while one Semi-Winter line (SW047) showed a significantly more rapid response to
      exogenous ABA, that corresponded to the high WUE indicated by delta13C
      measurements. This research illustrates the importance of examining natural
      variation at a physiological level for investigation of the underlying mechanisms
      influencing the diversity of carbon isotope discrimination values in the field
      and identifies natural variants in B. napus with improved WUE and potential
      relevant traits.

PMID- 29048602
TI  - Neural substrates underlying the effects of oxytocin: a quantitative meta
      analysis of pharmaco-imaging studies.
AB  - The hypothalamic peptide oxytocin (OT) is crucial in social adaptation and used
      to treat emotional and social deficits. Here, we conducted a systematic,
      quantitative meta-analysis of functional-MRI studies intranasally administering
      OT (IN-OT) to uncover neural substrates underlying the IN-OT effects and to
      elucidate differential IN-OT effects between healthy and clinical populations.
      Meta-analyses were conducted on 66 IN-OT fMRI studies, stratified by
      psychopathology, valence and sex. IN-OT increased bilateral amygdala, caudate
      head, and superior temporal activity in healthy individuals and increased dorsal
      anterior cingulate activity in patients. Moreover, IN-OT decreased amygdala
      activity in both patients and healthy individuals but did so to a greater degree
      in patients than healthy individuals. The OT-increased amygdala activity was only
      found on the negative social and affective processes, whereas the OT-decreased
      amygdala activity was mainly contributed by contrasts on negative-valenced
      processes. IN-OT increased parahippocampal activity and decreased amygdala
      activity during negative socio-affective processing. During positive socio
      affective processes, IN-OT increased caudate head activity. This study indicates
      convergent neural substrates and the underlying neuropsychological mechanisms for
      IN-OT effects on social and affective processes. The common and different effects
      of IN-OT on patients and healthy individuals and the modulation of OT effects by
      valence have critical implications.

PMID- 29048603
TI  - Postpartum depressive symptoms moderate the link between mothers' neural response
      to positive faces in reward and social regions and observed caregiving.
AB  - Postpartum depression may disrupt socio-affective neural circuitry and compromise
      provision of positive parenting. Although work has evaluated how parental
      response to negative stimuli is related to caregiving, research is needed to
      examine how depressive symptoms during the postpartum period may be related to
      neural response to positive stimuli, especially positive faces, given
      depression's association with biased processing of positive faces. The current
      study examined the association between neural response to adult happy faces and
      observations of maternal caregiving and the moderating role of postpartum
      depression, in a sample of 18- to 22-year old mothers (n = 70) assessed at 17
      weeks (s.d. = 4.7 weeks) postpartum. Positive caregiving was associated with
      greater precuneus and occipital response to positive faces among mothers with
      lower depressive symptoms, but not for those with higher symptoms. For mothers
      with higher depressive symptoms, greater ventral and dorsal striatal response to
      positive faces was associated with more positive caregiving, whereas the opposite
      pattern emerged for mothers with lower symptoms. There was no association between
      negative caregiving and neural response to positive faces or negative faces.
      Processing of positive stimuli may be an important prognostic target in mothers
      with depressive symptoms, given its link with healthy caregiving behaviors.

PMID- 29048605
TI  - Corrigendum.

PMID- 29048606
TI  - Contact Location and Neuropsychological Outcomes in Subthalamic Deep Brain
      Stimulation.
AB  - BACKGROUND: A host of influences contribute to cognitive and behavioral changes
      following deep brain stimulation. The location of the active cathode is likely an
      important variable but it has received little attention. OBJECTIVE: To determine
      whether active contact location relative to the subthalamic nucleus and other
      neighboring structures is related to nonmotor outcomes. METHODS: We identified a
      retrospective, cross-sectional sample of 46 patients who underwent subthalamic
      nucleus deep brain stimulation for treatment of idiopathic Parkinson's disease. T
      tests or nonparametric equivalents were used to detect baseline differences
      between unilateral left, unilateral right, and bilateral surgical groups.
      Correlation and partial correlational analyses identified relationships between
      contact location variables and alterations in cognitive, mood, quality of life,
      motor, and disease variables. RESULTS: Medial contact locations within the left
      subthalamic nucleus were correlated with improvements in self-reported mood (r12
      = -0.78, P = .001; 95% confidence interval [CI] = -0.43 to -0.93) but worsening
      semantic fluency (r26 = -0.38, P = .048; 95% CI = -0.01 to -0.66). Phonemic
      fluency worsened with more posterior left placement (r34 = 0.35, P = .036; 95% CI
      = 0.03 to 0.61). Memory outcome was related to right hemisphere stimulation
      voltage (r29 = -0.40, P = .022; 95% CI = -0.05 to -0.66), which is likely a proxy
      for variable electrode location. CONCLUSION: Location of the active contact is
      related to nonmotor outcomes, even in electrodes that are adequately placed. This
      is relevant to clinical care as there appears to be a trade-off between mood and
      fluency abilities that should be considered during surgical planning according to
      preoperative patient characteristics.

PMID- 29048604
TI  - Influence of DARPP-32 genetic variation on BOLD activation to happy faces.
AB  - Dopaminergic pathways play a crucial role in reward processing, and advanced age
      can modulate its efficiency. DARPP-32 controls dopaminergic function and is a
      chemical nexus of reward processing. In 61 younger (20-30 years) and older adults
      (54% ?) (65-74 years), we examined how blood-oxygen-level dependent (BOLD)
      activation to emotional faces, vary over genotypes at three single nucleotide
      polymorphism (SNPs), coding for DARPP-32 (rs879606; rs907094; 3764352). We also
      assessed age-magnification of DARPP-32 effects on BOLD activation. We found that
      major homozygote G, T or A genotypes, with higher cortical expression of DARPP
      32, higher dopamine receptor efficacy, and greater bias toward positive cues, had
      increased functional connectivity in cortical-subcortical circuits in response to
      happy faces, engaging the dorsal prefrontal cortex (DLPFC), fusiform gyrus (FG)
      and the midbrain (MB). Local BOLD response to happy faces in FG, and MB was age
      dependent, so that older carriers of the major G, T or A alleles showed lesser
      activation than minor genotypes. These genetic variants of DARPP-32 did not
      modulate BOLD response to angry faces, or engagement of the inferior occipital
      gyrus, to happy or angry faces. Taken together our results lend support for a
      potential role of DARPP-32 genetic variants in neural response to potential
      reward triggering cues.

PMID- 29048607
TI  - The Arabidopsis Chromatin-Remodeling Factor CHR5 Regulates Plant Immune Responses
      and Nucleosome Occupancy.
AB  - ATP-dependent chromatin-remodeling factors use the energy of ATP hydrolysis to
      alter the structure of chromatin and are important regulators of eukaryotic gene
      expression. One such factor encoded by CHR5 (Chromatin-Remodeling Factor 5) in
      Arabidopsis (Arabidopsis thaliana) was previously found to be involved in
      regulation of growth and development. Here we show that CHR5 is required for the
      up-regulation of the intracellular immune receptor gene SNC1 (SUPPRESSOR OF npr1
      1, CONSTITUTIVE1) and consequently the autoimmunity induced by SNC1 up
      regulation. CHR5 functions antagonistically with another chromatin-remodeling
      gene DDM1 (DECREASED DNA METHYLATION 1) and independently with a histone mono
      ubiquitinase HUB1 (HISTONE MONOUBIQUITINATION 1) in SNC1 regulation. In addition,
      CHR5 is a positive regulator of SNC1-independent plant immunity against the
      bacterial pathogen Pseudomonas syringae. Furthermore, the chr5 mutant has
      increased nucleosome occupancy in the promoter region relative to the gene body
      region at the whole-genome level, suggesting a global role for CHR5 in remodeling
      nucleosome occupancy. Our study thus establishes CHR5 as a positive regulator of
      plant immune responses including the expression of SNC1 and reveals a role for
      CHR5 in nucleosome occupancy which probably impacts gene expression genome wide.

PMID- 29048608
TI  - Zebrafish Locomotor Responses Reveal Irritant Effects of Fine Particulate Matter
      Extracts and a Role for TRPA1.
AB  - Exposure to fine particulate matter (PM) air pollution causes adverse
      cardiopulmonary outcomes. Yet, the limited capacity to readily identify
      contributing PM sources and associated PM constituents in any given ambient air
      shed impedes risk assessment efforts. The health effects of PM have been
      attributed in part to its capacity to elicit irritant responses. A variety of
      chemicals trigger irritant behavior responses in zebrafish that can be easily
      measured. The purposes of this study were to examine the utility of zebrafish
      locomotor responses in the toxicity assessment of fine PM and its chemical
      fractions and uncover mechanisms of action. Locomotor responses were recorded in
      6-day-old zebrafish exposed for 60 min in the dark at 26  degrees C to the
      extractable organic matter of a compressor-generated diesel exhaust PM (C-DEP)
      and 4 of its fractions (F1-F4) containing varying chemical classes of increasing
      polarity. The role of the transient receptor potential (TRP) cation channel
      TRPA1, a chemical sensor in mammals and zebrafish, in locomotor responses to C
      DEP, was also examined. Acrolein, an environmental irritant and known activator
      of TRPA1, and all extracts induced concentration-dependent locomotor responses
      whose potencies ranked as follows: polar F3 > weakly polar F2 > C-DEP > highly
      polar F4 > nonpolar F1, indicating that polar and weakly polar fractions that
      included nitro- and oxy-polyaromatic hydrocarbons (PAHs), drove C-DEP responses.
      Irritant potencies in fish positively correlated with mutagenic potencies of the
      same extracts in strains of Salmonella sensitive to nitro- and oxy-PAHs, further
      implicating these chemical classes in the zebrafish responses to C-DEP.
      Pharmacologic inhibition of TRPA1 blocked locomotor responses to acrolein and the
      extracts. Taken together, these data indicate that the zebrafish locomotor assay
      may help expedite toxicity screening of fine PM sources, identify causal chemical
      classes, and uncover plausible biological mechanisms.

PMID- 29048609
TI  - Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell
      proliferation and epithelial to mesenchymal transition of metastatic melanoma
      while inducing apoptosis.
AB  - Atypical protein kinase Cs (aPKC) are involved in cell cycle progression,
      tumorigenesis, cell survival and migration in many cancers. We believe that aPKCs
      play an important role in cell motility of melanoma by regulating cell signaling
      pathways and inducing epithelial to mesenchymal transition (EMT). We have
      investigated the effects of two novel aPKC inhibitors; 2-acetyl-1,3
      cyclopentanedione (ACPD) and 3,4-diaminonaphthalene-2,7-disulfonic acid (DNDA) on
      cell proliferation, apoptosis, migration and invasion of two malignant melanoma
      cell lines compared to normal melanocytes. Molecular docking data suggested that
      both inhibitors specifically bind to protein kinase C-zeta (PKC-zeta) and PKC
      iota (PKC-iota) and kinase activity assays were carried out to confirm these
      observations. Both inhibitors decreased the levels of total and phosphorylated
      PKC-zeta and PKC-iota. Increased levels of E-cadherin, RhoA, PTEN and decreased
      levels of phosphorylated vimentin, total vimentin, CD44, beta-catenin and
      phosphorylated AKT in inhibitor treated cells. This suggests that inhibition of
      both PKC-zeta and PKC-iota using ACPD and DNDA downregulates EMT and induces
      apoptosis in melanoma cells. We also carried out PKC-iota and PKC-zeta directed
      siRNA treatments to prove the above observations. Immunoprecipitation data
      suggested an association between PKC-iota and vimentin and PKC-iota siRNA
      treatments confirmed that PKC-iota activates vimentin by phosphorylation. These
      results further suggested that PKC-iota is involved in signaling pathways which
      upregulate EMT and which can be effectively suppressed using ACPD and DNDA. Our
      results summarize that melanoma cells proliferate via aPKC/AKT/NF-kappaB mediated
      pathway while inducing the EMT via PKC-iota/Par6/RhoA pathway. Overall, results
      show that aPKCs are essential for melanoma progression and metastasis, suggesting
      that ACPD and DNDA can be effectively used as potential therapeutic drugs for
      melanoma by inhibiting aPKCs.

PMID- 29048610
TI  - Evidence of lateral transmission of aggressive features between different types
      of breast cancer cells.
AB  - Breast cancer (BrC) is a major public health problem worldwide. The intra-tumoral
      heterogeneity and tumor cell plasticity importantly contribute to disease
      progression and treatment failure. However, the dynamic interactions between
      different tumor clones, as well as their contribution to tumor aggressiveness are
      still poorly understood. In this study, we provide evidence of a lateral
      transmission of aggressive features between aggressive and non-aggressive tumor
      cells, consisting of gain of expression of cancer stem cell markers, increased
      expression of CXCL12 receptors CXCR4 and CXCR7 and increased invasiveness in
      response to CXCL12, which correlated with high levels of secretion of pro
      inflammatory mediators G-CSF, GM-CSF, MCP-1, IL-8 and metalloproteinases 1 and 2
      by the aggressive cells. Noteworthy, we found no evidence of a TGF-beta
      participation in the inducible-invasive phenotype. Altogether, our results
      provide evidence of communication between tumor cells with different potentials
      for aggressiveness, which could influence intra-tumoral population dynamics
      promoting the emergence of clones with novel functions. Understanding these
      interactions will provide better targets for diagnosis, prognosis and therapeutic
      strategies.

PMID- 29048611
TI  - Human cytomegalovirus infection enhances cell proliferation, migration and
      upregulation of EMT markers in colorectal cancer-derived stem cell-like cells.
AB  - Increasing evidence suggests a link between persistent human cytomegalovirus
      (HCMV) infection and cancer. Although the role of HCMV in cancer is still
      elusive, recent studies revealed the presence of HCMV nucleic acids and proteins
      in different cancer types such as glioblastoma, colorectal, breast, and prostate
      cancers, and neuroblastoma. Although HCMV may not be directly associated with the
      neoplastic transformation, the presence of HCMV DNA in the tumorous tissue has
      been associated with altered clinical outcomes in cancer patients. However, the
      mechanisms involved in the association between colorectal cancer (CRC) and HCMV
      are unclear. In this study, we investigated the influence of HCMV infection on
      CRC or their derived cells. Proliferation and migration assays revealed a high
      infection efficiency in CRC-derived HT29 and SW480 'stem-like' cells. After 24,
      48 and 72 h of HCMV infection, both HT29 and SW480 parental and stem-like cells
      showed a significant increase in cell proliferation and viability (p<0.0001).
      Moreover, HCMV infection promoted cell migration. These results demonstrate a
      significant phenotypic alteration in the CRC cell line upon HCMV infection. Using
      epithelial to mesenchymal transition (EMT) assays, we demonstrated that the EMT
      markers and driver genes were upregulated during the virus infection. The WNT
      signaling pathway, which is associated with the proliferation and migration of
      CRC cells, was upregulated (6-fold) in HCMV-infected cells as compared to the non
      infected cells at day 7 from infection.

PMID- 29048613
TI  - miR-768-3p is involved in the proliferation, invasion and migration of non-small
      cell lung carcinomas.
AB  - Altered microRNA expression has been found to be a common feature of several
      cancers, including lung carcinomas. However, the possible roles of miR-768-3p in
      the pathological changes of lung carcinomas are still unknown. The aim of the
      present study was to investigate the expression and possible effects of miR-768
      3p in human non-small cell lung carcinomas (NSCLC). Eighty-three NSCLC patients
      attending the clinic of Kunming Hospital were invited to participate in the
      study. Their tumor samples were obtained for qRT-PCR analysis. Human NSCLC cell
      lines, A549 and HCC4006, were employed and transfected with either miR-768-3p
      mimics or miR-768-3p antagomir. Following transfection, the in vitro and in vivo
      proliferation, apoptosis fractions, migration and invasion of NSCLC cells were
      evaluated. The data revealed that: i) upregulated miR-768-3p in tumors were
      associated with the clinicopathological features of NSCLC patients; ii)
      inhibiting miR-768-3p function by miR-768-3p antagomir induced distinctly
      apoptosis and Fas/FasL expressional alteration of NSCLC cells; iii) miR-768-3p
      antagomir transduction also decreased the viability, migration and invasion, as
      well as MMP-2 and MMP-9 activities in A549 and HCC4006 cells; and iv) miR-768-3p
      antagomir transfection also inhibited the growth and proliferation of NSCLC
      xenografts in nude mice. The present results suggested that abnormal elevated miR
      768-3p in NSCLC tumors and cell lines played important roles in NSCLC
      carcinogenic progression, and the targeting of miR-768-3p might be a potential
      therapeutic strategy for the treatment of NSCLC.

PMID- 29048612
TI  - Regulation of ERK and AKT pathways by hepatitis B virus X protein via the Notch1
      pathway in hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) is the dominant risk factor for hepatocellular carcinoma
      (HCC). HBV X protein (HBx) plays crucial roles in HCC carcinogenesis. HBx
      interferes with several signaling pathways including the Notch1 pathway in HCC.
      In this study, we found that Notch1 was highly expressed in HCC, especially in
      large HCCs. Notch1 and HBx co-localized in HCC and their levels were positively
      correlated with each other. Notch1 expression was more elevated in HepG2.2.15
      cells than that in HepG2 cells. HBx activated the Notch1 pathway in HepG2.2.15
      cells. Suppression of HBx and the Notch1 pathway attenuated the growth of
      HepG2.2.15 cells. Notch1, ERK, and AKT pathways were inhibited after gamma
      secretase inhibitor treatment. Dual-specificity phosphatase 1 (DUSP1) and
      phosphatase and tensin homolog (PTEN) were upregulated after gamma-secretase
      inhibitor treatment and Hes1 inhibition. Luciferase reporter assays showed that
      Hes1 suppressed the promoters of DUSP1 and PTEN genes, which was reversed by
      gamma-secretase inhibitor treatment. Western blotting demonstrated that DUSP1
      dephosphorylated pERK and PTEN dephosphorylated pAKT. Collectively, we found a
      link among HBx, the Notch1 pathway, DUSP1/PTEN, and ERK/AKT pathways, which
      influenced HCC cell survival and could be a therapeutic target for HCC treatment.

PMID- 29048614
TI  - Brain lipid-binding protein promotes proliferation and modulates cell cycle in C6
      rat glioma cells.
AB  - Gliomas are the most common primary brain tumors affecting adults. Four grades of
      gliomas have been identified, namely, grades I-IV. Brain lipid-binding protein
      (BLBP), which functions in the intracellular transport of fatty acids, is
      expressed in all grades of human gliomas. The glioma cells that are cultured in
      vitro are grouped into the BLBP-positive and BLBP-negative cell lines. In the
      present study, we found that C6 rat glioma cells was a distinct type of BLBP
      negative cell line. Our results confirmed that in the C6 cells, the expression of
      exogenous BLBP increased the proliferation and percentage of cells in the S
      phase, in the culture medium containing 10 or 1% FBS. Moreover, exogenous BLBP
      was found to downregulate the tumor suppressors p21 and p16 in the 1% FBS culture
      medium, but only p21 in the 10% FBS culture medium. The results of the xenograft
      model assay showed that exogenous BLBP also stimulated tumor formation and
      downregulated p21 and p16. In conclusion, our study demonstrated that exogenous
      BLBP promoted proliferation of the C6 cells in vitro and facilitated tumor
      formation in vivo. Therefore, BLBP expression in glioma cells may promote cell
      growth by inhibiting the tumor suppressors.

PMID- 29048615
TI  - Overexpression of RAB34 correlates with poor prognosis and tumor progression in
      hepatocellular carcinoma.
AB  - RAB34, a protein belonging to the RAB family, is involved in protein transport,
      repositioning of lysosomes and activation of micropinocytosis. However, few
      studies have reported its function in human epithelial cancers.
      Immunohistochemistry (IHC) and western blotting were used to detect expression of
      RAB34 at the tissue and cell levels. Cell Counting Kit-8 (CCK-8), EDU assay and
      flow cytometry were used for analyzing cell proliferation. Transwell and scratch
      wound healing assays were used for assessing cell migration ability. Western
      blotting was used for detecting expression of E-cadherin and N-cadherin. In the
      present study, we found that both DNA copy and protein level of RAB34 were
      upregulating in human hepatocellular carcinoma (HCC) tissues when compared with
      that in adjacent tissues. Analysis of the correlation between RAB34 expression
      and clinicopathological features showed that patients with overexpression of
      RAB34 consistently had large tumor size, vessel invasion and poor tumor grade.
      Furthermore, overall survival analysis showed that patients with upregulated
      expression of RAB34 were associated with poor prognosis. Moreover, cell function
      experiments showed that suppression of RAB34 led to a lower proliferation rate
      and migration ability. In addition, this phenomenon may be attributed to cell
      cycle phase G1 arrest and mesenchymal-epithelial transition under condition of
      RAB34 suppression. The present study demonstrated that RAB34 plays an important
      role in the initiation and progression of HCC. Our results suggest a new
      therapeutic target for the clinical treatment of HCC.

PMID- 29048616
TI  - The receptor for activated protein kinase C promotes cell growth, invasion and
      migration in cervical cancer.
AB  - Cervical cancer is one of the most common malignant tumors in women all over the
      world. However, the exact etiology of cervical cancer remains unclear. The
      receptor for activated protein kinase C (RACK1) is reported to be involved in
      tumorigenesis and tumor progression. Besides, the prognostic value of RACK1 in
      several kinds of tumors has been identified. However, there are limited studies
      on the functional role of RACK1 in cervical cancer. In this study, we tested the
      expression level of RACK1 by immunohistochemistry and western blot technologies
      and find that it is upregulated in cervical cancer. Colony formation and CCK8
      assays indicate that RACK1 promotes cell proliferation in CaSki cervical cancer
      cells. While the silence of RACK1 decreases the cell proliferation in CCK8
      analysis. beta-galactosidase staining suggests that RACK1 decreases cell
      senescence in cervical cancer cells. Invasion and migration assay show that RACK1
      promotes the invasion and migration of cervical cancer cells. Also, when RACK1
      was silenced, it exerts the opposite result. Furthermore, the mRNA expression
      levels of MMP-3, MMP-9 and MMP-10 were upregulated in RACK1-overexpressed CaSki
      cells by qPCR analysis. RACK1 also induces S phase accumulation in cell cycle
      analysis and suppresses cell apoptosis in cervical cancer cells. Flow cytometry
      analysis of mitochondria functions suggests that RACK1 increases the
      mitochondrial membrane potential (Deltapsim) levels to prevent mitochondrial
      apoptosis in cervical cancer cells. To explore the possible mechanism of RACK1,
      we tested and found that RACK1 upregulates the expression of NF-kappaB, cyclin D1
      and CDK4 and downregulates the expression of p53, p38, p21 and STAT1 in cervical
      cancer cells. These results suggest that RACK1 promotes cell growth and invasion
      and inhibits the senescence and apoptosis in cervical cancer cells probably by
      affecting the p53 pathway.

PMID- 29048617
TI  - MEK inhibitor, PD98059, promotes breast cancer cell migration by inducing beta
      catenin nuclear accumulation.
AB  - Abnormal activation of the RAF/MEK/ERK signaling pathway has been observed in
      breast cancer. Thus, a number of MEK inhibitors have been designed as one
      treatment option for breast cancer. Although some studies have found that these
      MEK inhibitors inhibit the growth of a variety of human cancer cells, some trials
      have shown that the use of MEK inhibitors as a treatment for breast cancer does
      not adequately improve survival for unknown reasons. In the present study, MEK
      inhibitor PD98059 was used to evaluate its anticancer effects on human breast
      cancer MCF-7 and MDA-MB-231 cells and to explore the possible mechanism of
      action. Our results revealed that MEK inhibitor PD98059 exhibited
      antiproliferative effects in a dose- and time-dependent manner in MCF-7 and MDA
      MB-231 breast cancer cells. Conversely, incubation of MCF-7 and MDA-MB-231 cells
      with PD98059 promoted their migration. Further investigation disclosed that the
      enhanced ability of migration promoted by PD98059 was dependent on beta-catenin
      nuclear translocation in the MCF-7 and MDA-MB-231 cells. Subsequent experiments
      documented that activation of EGFR signaling induced by PD98059 increased the
      amount of beta-catenin in the nucleus. Taken together, our findings may elucidate
      a possible mechanism explaining the ineffectiveness of MEK inhibitors in breast
      cancer treatment and improve our understanding of the role of MEK in cancer.

PMID- 29048618
TI  - Dual action of NSC606985 on cell growth and apoptosis mediated through PKCdelta
      in prostatic cancer cells.
AB  - Chemotherapy is a vital therapeutic strategy for castration-resistant prostate
      cancer (CRPC). We have previously shown that NSC606985 (NSC), a camptothecin
      (CPT) analog, induced cell apoptosis via interacting with topoisomerase I (Topo
      I) in prostate cancer cells. In the present study, the effect and mechanism of
      CPT analogs in LAPC4 cells were investigated. LAPC-4 cells were treated with NSC,
      CPT, and topotecan. Cell proliferation, apoptosis, and protein kinase Cdelta
      (PKCdelta) subcellular activation were measured at different doses and time
      points, with or without PKCdelta inhibition or knockdown of PKCdelta expression.
      NSC at doses ranging from 10 to 100 nM induced a dose-dependent increase in
      viable cell number and DNA biosynthesis with mild cell apoptosis, whereas, at
      doses ranging from 500 nM to 5 mM, NSC produced a dose-dependent decrease in cell
      proliferation and DNA biosynthesis with a significant induction of cell
      apoptosis. Both NSC-induced cell proliferation and apoptosis were blocked by
      knockdown of PKCdelta with a specific RNAi, or by the co-administration of
      rottlerin, a PKCdelta inhibitor. Moreover, NSC produced a dose-dependent
      subcellular activation of PKCdelta. The dose-dependent dual action of NSC is
      mediated at least in part through the differential subcellular activation of
      PKCdelta in LAPC4 cells. The demonstration of a differential cell response to
      camptothecin analogs would facilitate the identification of biomarker(s) to CPT
      sensitivity and promote the personalization of CPT chemotherapy in CRPC.

PMID- 29048619
TI  - MicroRNA-381 serves as a prognostic factor and inhibits migration and invasion in
      non-small cell lung cancer by targeting LRH-1.
AB  - Accumulating evidence has demonstrated that aberrant miRNAs were involved in
      carcinogenesis and tumor progression by regulating oncogenes or tumor suppressor
      expression. Dysregulation of miR-381 has been reported in different tumors.
      However, the clinical roles and underlying mechanism in non-small cell lung
      cancer (NSCLC) remains to be elucidated. We found the expression of miR-381 was
      significantly downregulated in both NSCLC tissues and cell lines. Clinical
      analysis revealed the reduced miR-381 was obviously associated with advanced TNM
      stage and lymph node metastasis. Moreover, we disclosed that miR-381 was a novel
      independent prognostic marker for predicting 5-year survival of NSCLC patients.
      The ectopic overexpression of miR-381 inhibited cell migration and invasion in
      vitro and in vivo. Notably, miR-381 could modulate LRH-1 by directly binding to
      its 3'-UTR. In clinical samples of NSCLC, miR-381 inversely correlated with LRH-1
      expression, which performed positive roles in NSCLC migration and invasion.
      Alteration of LRH-1 expression at least partially abolished the migration and
      invasion of miR-381 on NSCLC cells. Here, we identified LRH-1 as a functional
      target of miR-381 in NSCLC. In conclusion, our data indicated that miR-381
      inhibited migration and invasion of NSCLC by targeting LRH-1, and may represent a
      novel potential therapeutic target and prognostic marker for NSCLC.

PMID- 29048620
TI  - DNA methylation and histone modifications as epigenetic regulation in prostate
      cancer (Review).
AB  - Prostate cancer is the second most commonly diagnosed cancer in men in Poland
      after lung cancer and the third leading cause of cancer-related mortality after
      lung and colon cancer. The etiology of most cases of prostate cancer are not
      fully known, and therefore it is essential to search for the molecular basis of
      prostate cancer and markers for the early diagnosis of this type of cancer.
      Epigenetics deals with changes in gene expression that are not determined by
      changes in the DNA sequence. Epigenetic changes refer to changes in the structure
      of DNA, which are the result of DNA modification after replication and/or post
      translational modification of proteins associated with DNA. In contrast to
      mutations, epigenetic changes are reversible and occur very rapidly. The major
      epigenetic mechanisms include DNA methylation, modification of histone proteins,
      chemical modification and chromatin remodeling changes in gene expression caused
      by microRNAs (miRNAs). Epigenetic changes play an important role in malignant
      transformation and can be specific to types of cancers including prostate cancer.

PMID- 29048621
TI  - Irisin reverses the IL-6 induced epithelial-mesenchymal transition in
      osteosarcoma cell migration and invasion through the STAT3/Snail signaling
      pathway.
AB  - As a novel discovered myokine, irisin is considered to be a promising candidate
      for the treatment of metabolic disorders and cancer. However, little is known
      about the anti-metastasic effect of irisin on osteosarcoma cells and its
      underlying mechanisms. In the present study, we aimed to explore the effect of
      irisin on the migration and invasion of osteosarcoma cells and the underlying
      mechanisms involved. Viability and proliferation of osteosarcoma cells were
      examined by MTT assay. Then, by using scratch wound healing assay and Transwell
      assays, we evaluated migratory and invasive ability of the cells, respectively.
      Moreover, the expression of epithelial-to-mesenchymal transition (EMT) markers
      were determined by qPCR, western blot and immunofluorescence staining after
      treatment with IL-6 and irisin. Furthermore, the expression of ERK, p38, STAT3
      and Snail were detected by western blot analysis. Finally, an inhibitor of STAT3,
      WP1066 was applied to testify the effect of irisin on the expression of EMT
      markers and Snail. It was found that irisin treatment significantly suppressed
      the proliferation, migration and invasion of osteosarcoma cells. Furthermore,
      irisin reversed the IL-6-induced epithelial-mesenchymal transition (EMT) in
      osteosarcoma cells by regulating the expression of E-cadherin, N-cadherin,
      vimentin, fibronectin, MMP-2, MMP-7 and MMP-9. In addition, irisin suppressed the
      IL-6-activated phosphorylation of STAT3 and the expression of Snail in
      osteosarcoma cells. Finally, blockade of STAT3 by WP1066 (a STAT3 inhibitor)
      further enhanced the effect of irisin on the EMT and Snail expression in
      osteosarcoma cells. Collectively, our findings revealed that irisin may play a
      critical role in the IL-6-induced EMT of osteosarcoma cells via the STAT3/Snail
      signaling pathway.

PMID- 29048622
TI  - Enhancement of cytotoxic effects of gemcitabine by Dclk1 inhibition through
      suppression of Chk1 phosphorylation in human pancreatic cancer cells.
AB  - Although gemcitabine (GEM) is frequently used in the treatment of pancreatic
      cancer, the effects are limited. To increase the inhibitory effect of GEM, the
      identification of a molecular target is needed. Recent studies have revealed that
      doublecortin-like kinase 1 (Dclk1) positively regulates tumor growth, invasion,
      metastasis, factors related to epithelial-mesenchymal transition (EMT),
      pluripotency, angiogenesis, and anti-apoptosis in pancreatic cancer cells.
      Therefore, Dclk1 is a potential therapeutic target for pancreatic cancer.
      However, the Dclk1-signaling pathway including its substrate proteins remains to
      be elucidated. To identify the candidate substrate proteins phosphorylated by
      Dclk1, we performed a cancer-related phosphorylated protein microarray using
      Dclk1-inhibited MIA Paca2 cells. Expression levels of phosphorylated cdc25A (p
      cdc25A) and phosphorylated Chk1 (p-Chk1), belonging to the ATR pathway, were
      decreased by treatment with Dclk1 inhibitor LRRK2-IN-1 (LRRK), indicating Dclk1
      involvement in the ATR pathway. Consistent with this finding, the GEM-induced p
      Chk1 expression was significantly decreased by treatment with LRRK. Notably,
      combined treatment with GEM and LRRK allowed cell cycle progression without
      arresting at S phase, while individual treatment with GEM induced cell cycle
      arrest at S phase. In addition, combined treatment with GEM and LRRK increased
      the number of gamma-H2AX-positive cells compared with that upon individual
      treatments. Moreover, LRRK alone, and combined treatment with GEM and LRRK,
      induced caspase-3 activation and PARP1 cleavage, in contrast to treatment with
      GEM alone. Finally, combined treatment with GEM and LRRK significantly reduced
      cell survival compared to individual treatment with GEM. These results indicate
      that Dclk1 inhibition in combination with GEM treatment offers a novel approach
      to treat pancreatic cancer cells.

PMID- 29048623
TI  - VEGFR3 inhibition chemosensitizes lung adenocarcinoma A549 cells in the tumor
      associated macrophage microenvironment through upregulation of p53 and PTEN.
AB  - In lung adenocarcinoma, loss of p53 and PTEN in tumors are associated with
      decreased response to chemotherapy and decreased survival. A means to
      pharmacologically upregulate p53 and PTEN protein expression could improve the
      prognosis of patients with p53- and PTEN-deficient tumors. In the present study
      we revealed that vascular endothelial growth factor receptor 3 (VEGFR3)
      inhibition in lung adenocarcinoma cells was associated with improved expression
      levels of both p53 and PTEN in the tumor-associated macrophage (TAM)
      microenvironment. Inhibition of VEGFR3 in lung adenocarcinoma cells was
      associated with growth arrest and decreased migration and invasion. The
      upregulation of p53 and PTEN protein expression after VEGFR3 inhibition decreased
      chemotherapy resistance and improved chemosensitivity in co-cultured A549 cells
      in which p53 and PTEN expression were decreased. Finally, we demonstrated that
      TAMs promoted the expression of VEGF-C and its receptor VEGFR3. Western blot
      analysis revealed the co-cultured A549 cells with TAMs are a primary source of
      VEGF-C and VEGFR3 in the tumor microenvironment. Our studies revealed that VEGFR3
      inhibition may be a pharmacological means to upregulate p53 and PTEN protein
      expression and improve the outcome of patients with p53- and PTEN-deficient
      tumors.

PMID- 29048624
TI  - Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric
      cancer cells in vitro and xenograft nude mice in vivo.
AB  - Gastric cancer is reported as one of the leading factors resulting in tumor
      related death worldwide. However, the therapies to suppress gastric cancer are
      still limited and the emergence of drug resistance makes it necessary to develop
      new and effective anticancer drugs and combinational chemotherapy schemes.
      Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various
      pharmacological activities, including anticancer. In this study, we investigated
      the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance.
      The findings suggested that LIQ, when applied in single therapy, could moderately
      inhibit the proliferation and migration of DDP-resistant gastric cancer cells,
      SGC7901/DDP. DDP and LIQ in combination induced G0/G1 cell cycle arrest to
      suppress the proliferation of gastric cancer cells, which were associated with
      the decrease of cyclin D1, cyclin A and cyclin-dependent kinase 4 (CDK4) and
      increase of p53 and p21. In addition, LIQ combined with DDP significantly induce
      apoptosis and autophagy both in vitro and in vivo through enhancing cleavage of
      caspase-8/-9/-3 and PARP, as well as LC3B and Beclin 1 expression. Significantly,
      the two drugs, when used in combination, prevented gastric cancer cell xenografts
      in nude mice in vivo. Together, the results revealed that application of DDP and
      LIQ in combination possessed a potential value against the growth of human
      gastric cancer with DDP resistance.

PMID- 29048625
TI  - Myeloid zinc finger 1 protein is a key transcription stimulating factor of
      PYROXD2 promoter.
AB  - Previous studies revealed that PYROXD2 was more highly expressed in normal liver
      tissue and liver cell lines than in cancer tissue and cancer cell lines, which
      indicated that decreased PYROXD2 expression may be involved in
      hepatocarcinogenesis. To identify the mechanisms which regulate PYROXD2 gene
      transcription, we constructed a series of luciferase reporter plasmids and used
      them to perform luciferase-based reporter assays with HepG2, Sk-hep1, L02 and
      293T cells with the purpose of characterizing the PYROXD2 reporter region. Our
      results revealed that the transcription factor myeloid zinc finger 1 (MZF1) is
      necessary for PYROXD2 gene transcription and that it functions as a trans
      activator. DNA binding assays revealed that the MZF1 protein binds to the cis
      element TGGGGA located in the -320/-312 region of the PYROXD2 promoter. This
      promoter had a significantly enhanced activity when the MZF1 protein was
      overexpressed and a significantly decreased activity when the MZF1 protein
      expression was silenced. However, MZF1 gene expression was not significantly
      correlated with PYROXD2 protein expression in the samples of resected tumor
      tissues, which revealed that the PYROXD2 promoter transcription activity was
      determined by the aggregated effect of numerous transcription factors. This
      finding may be helpful in understanding the underlying mechanism which regulates
      the PYROXD2 expression.

PMID- 29048626
TI  - MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by
      directly targeting PAK4.
AB  - Glioblastoma (GBM), which is characterised by rapid growth, cellular
      heterogeneity, angiogenesis, extensive invasion, hypoxia and necrosis, is the
      most common histological subtype of glioma in adults. MicroRNA (miRNA)
      dysregulation is a common feature of human cancers, including GBM. Previous
      studies have suggested that miRNAs are a novel class of regulatory molecules in
      various human cancers. Therefore, miRNAs may be investigated as a novel candidate
      and screening tool in the clinical diagnosis, therapy and prognosis of GBM.
      Recent accumulating evidence has demonstrated that miRNA-485 (miR-485) is
      involved in the development and progression of several types of human cancers.
      However, the expression level, exact role and underlying mechanisms of miR-485 in
      GBM remain unclear. In this study, miR-485 was downregulated in both GBM tissue
      specimens and cell lines. miR-485 overexpression inhibited GBM cell
      proliferation, colony formation, migration and invasion; increased apoptosis in
      vitro; and reduced tumour growth in vivo. In addition, p21-activated kinase 4
      (PAK4) was demonstrated to be a direct and functional target of miR-485 in GBM.
      Furthermore, PAK4 was upregulated in GBM tissues and negatively correlated with
      miR-485 expression. Moreover, PAK4 knockdown exhibited a similar effect to miR
      485 overexpression in GBM cells. Enforced expression of PAK4 rescued miR-485
      tumour-suppressor functions in GBM cells. miR-485 inhibited the activation of the
      AKT and ERK signalling pathways in GBM. These results indicate that miR-485 acts
      as a tumour suppressor in GBM by, at least partially, directly targeting PAK4 and
      regulating the AKT and ERK signalling pathways. Thus, miR-485 may be a potential
      target for the treatment of patients with GBM.

PMID- 29048627
TI  - SLC7A11, a component of cysteine/glutamate transporter, is a novel biomarker for
      the diagnosis and prognosis in laryngeal squamous cell carcinoma.
AB  - Solute carrier family 7, membrane 11 (SLC7A11) or (xCT) is a component of the
      cysteine-glutamate transporter, which plays a critical role in glutathione
      homeostasis which is important to protect cells from oxidative stress. SLC7A11 is
      distributed in various tissues and participates in the occurrence of a number of
      diseases, particularly in the pathogenesis of malignant tumors, but its role in
      laryngeal cancer development has not yet been clearly defined. The objective of
      the present study was to investigate the role of SLC7A11 in laryngeal squamous
      cell carcinoma (LSCC). We conducted immunohistochemistry and RT-PCR to evaluate
      the protein and mRNA levels of SLC7A11 in LSCC and in control tissues,
      respectively. The knockdown experiments were conducted with SLC7A11 short hairpin
      RNA (shRNA) lentivirus, and the protein and mRNA levels of SLC7A11 were assessed
      by RT-PCR and western blotting. The functional study of SLC7A11 in vitro was
      conducted by MTT assay, and the effects on the cell cycle were detected using
      flow cytometry. Immunohistochemical results revealed that the expression levels
      of SLC7A11, Ki-67 and p53 in LSCC tissues were higher than those in laryngeal
      dysplasia tissues. The Spearman rank correlation analysis revealed that the
      expression of SLC7A11 was positively correlated with the expression of p53 and Ki
      67. Cox regression analysis and Kaplan-Meier plots confirmed that the expression
      levels of SLC7A11 were a prognostic factor for overall survival (OS) rates and
      postoperative recurrence of LSCC. Moreover, the functional study of SLC7A11 in
      vitro revealed that knockdown of SLC7A11 using shRNA inhibited cell proliferation
      by inducing cell cycle arrest at the G1 phase. Immunohistochemical and RT-PCR
      results and knockdown experiments of SLC7A11 revealed that SLC7A11 was involved
      in the progression of LSCC, and may provide clinical information for the
      evaluation of OS rates and postoperative recurrence of LSCC. Collectively, these
      observations suggest that SLC7A11 may be a vital biomarker for the diagnosis and
      prognosis in human LSCC, and targeting SLC7A11 appears to be a potentially
      significant method for LSCC treatment.

PMID- 29048628
TI  - Low heme oxygenase-1 expression promotes gastric cancer cell apoptosis, inhibits
      proliferation and invasion, and correlates with increased overall survival in
      gastric cancer patients.
AB  - Heme oxygenase-1 (HO-1) plays a key role in anti-oxidation, anti-apoptosis, and
      anti-proliferation in various types of cancers. However, the relationship between
      HO-1 expression and gastric cancer development remains largely unknown. In this
      study, the protein expression of HO-1 in human gastric cancer was measured by
      immunohistochemistry on paraffin sections of 89 paired gastric carcinoma tissues
      and adjacent non-cancer tissues. The correlation of HO-1 expression with 5-year
      overall survival rate was estimated. The effects of decreased HO-1 expression by
      two strands of small interfered RNAs (siRNAs) on cell apoptosis, proliferation,
      and invasion of gastric cancer cell lines were examined by flow cytometry, the
      MTT assay, and the cell migration assay, respectively. High expression of HO-1
      was detected in 11.2% (10/89) of gastric carcinoma tissues, compared with 1.1%
      (1/89) in matched adjacent normal tissues, and correlated with a decreased
      survival rate in gastric cancer patients. There were no significant correlations
      between HO-1 expression and clinical characteristics. Downregulation of HO-1
      expression using two strands of siRNAs promoted apoptosis and inhibited the
      proliferation and invasion of two gastric cancer cell lines, SGC7901 and MKN-28
      cells. This study demonstrated that HO-1 plays a vital role in the development of
      gastric cancer and may serve as a therapeutic target of this type of cancer.

PMID- 29048630
TI  - Metastatic genes targeted by an antioxidant in an established radiation- and
      estrogen-breast cancer model.
AB  - Breast cancer remains the second most common disease worldwide. Radiotherapy,
      alone or in combination with chemotherapy, is widely used after surgery as a
      treatment for cancer with proven therapeutic efficacy manifested by reduced
      incidence of loco-regional and distant recurrences. However, clinical evidence
      indicates that relapses occurring after radiotherapy are associated with
      increased metastatic potential and poor prognosis in the breast. Among the
      anticarcinogenic and antiproliferative agents, curcumin is a well-known major
      dietary natural yellow pigment derived from the rhizome of the herb Curcuma longa
      (Zingiberaceae). The aim of the present study was to analyze the differential
      expression of metastatic genes in radiation- and estrogen-induced breast cancer
      cell model and the effect of curcumin on such metastatic genes in breast
      carcinogenesis. Expression levels of TGF-alpha and TGFbeta1 genes were
      upregulated in MCF-10F and downregulated in Tumor2 cell lines treated with
      curcumin. Expression levels of other genes such as caspase 9 and collagen 4 A2
      were upregulated in both MCF-10F and Tumor2-treated cell lines. Integrin alpha5
      and cathepsin B and D decreased its expression in Tumor2, whereas E-Cadherin, c
      myc and CD44 expressions were only increased in MCF-10F. It can be concluded that
      metastatic genes can be affected by curcumin in cancer progression and such
      substance can be used in breast cancer patients with advanced disease without
      side-effects commonly observed with therapeutic drugs.

PMID- 29048629
TI  - Inhibition of neuroblastoma proliferation by PF-3758309, a small-molecule
      inhibitor that targets p21-activated kinase 4.
AB  - Neuroblastoma is the most common extracranial solid childhood tumor. Despite the
      availability of advanced multimodal therapy, high-risk patients still have low
      survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many
      cellular processes in cancer cells, including migration, polarization and
      proliferation. However, the role of PAK4 in neuroblastoma remains unclear. In the
      present study, we demonstrated that PAK4 was overexpressed in neuroblastoma
      tissues and was correlated with tumor malignance and prognosis. To investigate
      the function of PAK4 in neuroblastoma, we used a small-molecule inhibitor that
      targets PAK4, that is, PF-3758309. Our results showed that PF-3758309
      significantly induced cell cycle arrest at the G1 phase and apoptosis in
      neuroblastoma cell lines. Meanwhile, the inhibition of PAK4 by PF-3758309
      increased the expression of CDKN1A, BAD and BAK1 and decreased the expression of
      Bcl-2 and Bax. In addition, we screened the target genes of PAK4 by PCR array and
      found that 23 genes were upregulated (including TP53I3, TBX3, EEF1A2, CDKN1A,
      IFNB1 and MAPK8IP2) and 20 genes were downregulated (including TNFSF8, Bcl2-A1,
      Bcl2L1, SOCS3, BIRC3 and NFKB1) after PAK4 inhibition by PF-3758309. Moreover,
      PAK4 was found to regulate the cell cycle and apoptosis via the ERK signaling
      pathway. In conclusion, the present study demonstrated, for the first time, the
      expression and function of PAK4 in neuroblastomas and the inhibitory effect of PF
      3758309, which deserves further investigation as an alternative strategy for
      neuroblastoma treatment.

PMID- 29048631
TI  - Autophagy induction enhances tetrandrine-induced apoptosis via the AMPK/mTOR
      pathway in human bladder cancer cells.
AB  - Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the roots of
      Stephania tetrandra is a traditional Chinese medicine and exerts anticancer
      capacity in various types of cancers. Previous studies have shown that
      tetrandrine induces apoptosis in bladder cancer cells via activation of the
      caspase cascade. However, the underlying mechanism has not yet been reported.
      Autophagy is a cellular process involved in the degradation of broken proteins
      and aging organelles to maintain homeostasis. Recent studies indicate that
      autophagy is implicated in cancer therapy. Thus, we focused on the correlation
      between autophagy and apoptosis upon tetrandrine treatment in human bladder
      cancer cells. Firstly, our results observed a marked increase in autophagic
      double-membrane vacuoles and fluorescent puncta of red fluorescence protein-green
      fluorescence protein-LC3 (GRP-RFP-LC3) upon tetrandrine treatment, as evidenced
      by transmission electron microscopy and confocal fluorescence microscopy.
      Secondly, the expression of LC3-II was increased in tetrandrine-treated T24 and
      5637 cells in a time- and concentration-dependent manner. Subsequently,
      downregulation of p62 and LC3 turnover assay further confirmed that tetrandrine
      induced autophagic flux in bladder cancer T24 and 5637 cells. Thirdly, the
      protein levels of phosphorylated-AMP-activated protein kinase (AMPK) and
      phosphorylated-acetyl-coenzyme A carboxylase (ACC) were upregulated in the
      tetrandrine-treated cells, while the mammalian target of rapamycin (mTOR)-related
      proteins were downregulated. Moreover, AICAR, a common AMPK activator, further
      increased the expression the LC3-II, while AMPK inhibitor compound C partially
      reversed the LC3-II protein levels in bladder cancer T24 cells. Finally, AICAR
      significantly reinforced the growth inhibition and apoptosis induction of
      tetrandrine in T24 and 5637 cells, while compound C had an opposite effect,
      suggesting that AMPK-mediated autophagy enhanced the cytotoxic and pro-apoptosis
      effect of tetrandrine in human bladder cancer cells. Taken together, the present
      study showed that tetrandrine induced autophagy in human bladder cancer cells by
      regulating the AMPK/mTOR signaling pathway, which contributed to the apoptosis
      induction by tetrandrine, indicating that tetrandrine may be a potential
      anticancer candidate for the treatment of bladder cancer, and autophagy may be a
      possible mechanism for cancer therapy.

PMID- 29048632
TI  - MicroRNA-1297 inhibits metastasis and epithelial-mesenchymal transition by
      targeting AEG-1 in cervical cancer.
AB  - Accumulating evidence has demonstrated that aberrant miRNAs contribute to
      cervical cancer (CC) development and progression. However, the roles of various
      miRNAs in CC remain to be determined. In the present study, we confirmed that a
      decreased miR-1297 expression was present in CC tissues and cell lines. Our
      clinical analysis revealed that the downregulated miR-1297 expression was
      significantly correlated with poor prognostic features including lymph node
      metastasis and lymphovascular space invasion. Moreover, we confirmed that miR
      1297 was a novel independent prognostic marker for predicting the 5-year survival
      of CC patients. The ectopic overexpression of miR-1297 inhibited cell migration,
      invasion and EMT progression, while downregulated miR-1297 reversed these
      effects. In addition, miR-1297 regulated AEG-1 by directly binding to its 3'-UTR.
      In clinical samples of CC, miR-1297 was inversely correlated with AEG-1, which
      was upregulated in CC. Alteration of AEG-1 expression at least partially
      abolished the migration, invasion and EMT progression effects of miR-1297 on CC
      cells. In conclusion, our results indicated that miR-1297 functioned as a tumor
      suppressor gene in regulating the EMT and metastasis of CC via targeting of AEG
      1, and may represent a novel potential therapeutic target and prognostic marker
      for CC.

PMID- 29048633
TI  - In vitro and in vivo anti-primary effusion lymphoma activities of fucoidan
      extracted from Cladosiphon okamuranus Tokida.
AB  - Primary effusion lymphoma (PEL) caused by Kaposi's sarcoma-associated herpesvirus
      (KSHV) is characterized by lymphomatous effusion in body cavities and poor
      prognosis. There is still no effective treatment for PEL. Fucoidan, a major
      sulfated polysaccharide isolated from brown seaweeds, has an attractive array of
      bioactivities such as cancer inhibition. However, the effects of fucoidan on PEL
      cells remain unclear. We investigated the anti-PEL effects of fucoidan obtained
      from Cladosiphon okamuranus Tokida cultivated in Okinawa. Fucoidan dose
      dependently inhibited the proliferation of KSHV-infected PEL cell lines, and
      provoked G1 cell cycle arrest, which was accompanied by CDK4 and CDK6
      downregulation. Fucoidan also induced apoptosis of PEL cells through caspase-3, 
      8 and -9 activation; this occurred partly through the downregulation of anti
      apoptotic Bcl-xL, Mcl-1 and XIAP proteins. Fucoidan also suppressed nuclear
      factor-kappaB, activator protein-1 (AP-1), and T-lymphokine-activated killer cell
      originated protein kinase (TOPK) signaling pathways through inhibition of
      phosphorylation of IkappaBalpha and TOPK, and the expression of AP-1 family
      proteins, JunB and JunD. Oral administration of fucoidan effectively inhibited
      the development of PEL cells and ascites in a xenograft SCID mouse model, with
      minimal serious adverse effects. Notably, native fucoidan exhibited a more
      efficient anti-PEL effect than nanoparticle fucoidan. These preclinical findings
      highlight the anti-PEL actions of fucoidan, suggesting it could be potentially
      useful for the prevention and treatment of PEL.

PMID- 29048634
TI  - [Retracted] Efficacy of dual-functional liposomes containing paclitaxel for
      treatment of lung cancer.
AB  - Following the publication of this article, the authors find that they are not
      able to reproduce the results presented in this paper. Consequently, the authors
      have decided to retract this paper from publication. All of the authors agree to
      this retraction. The authors sincerely regret this decision, and apologize to the
      Editor and to the readership of the Journal for any inconvenience caused. [the
      original article was published in Oncology Reports 33: 783-791, 2015; DOI:
      10.3892/or.2014.3644].

PMID- 29048635
TI  - Novel focal adhesion kinase 1 inhibitor sensitizes lung cancer cells to radiation
      in a p53-independent manner.
AB  - Focal adhesion kinase 1 (FAK1) is known to promote tumor progression and
      metastasis by controlling cell movement, invasion, survival and the epithelial-to
      mesenchymal transition in the tumor microenvironment. As recent reports imply
      that FAK1 is highly associated with tumor cell development and malignancy, the
      inhibition of FAK1 activity could be an effective therapeutic approach for
      inhibiting the growth and metastasis of tumor cells. In this study, we aimed to
      determine the effect of a novel synthetic FAK1 inhibitor 2-[2-(2-methoxy-4
      morpholin-4-yl-phenylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-N-methyl
      benzamide, (MPAP) on lung cancer cells. MPAP suppressed cancer cell proliferation
      and the phosphorylation of FAK1. Combined treatment with MPAP and irradiation
      (IR) showed enhanced suppression of cancer cell proliferation in wild-type p53
      cells and more intense suppression in p53-null cells. In addition, the
      combination treatment effectively induced G1 cell cycle arrest in a p53
      independent manner. In an in vivo tumor xenograft mouse model, treatment with
      both MPAP and IR reduced tumor growth more than the treatment with IR or MPAP
      alone. Overall, these data demonstrate that the radiosensitizing effect of MPAP
      is mediated by the regulation of retinoblastoma protein (RB) phosphorylation in a
      p53-independent manner.

PMID- 29048636
TI  - Genome-wide study of ER-regulated lncRNAs shows AP000439.3 may function as a key
      regulator of cell cycle in breast cancer.
AB  - Estrogen receptor (ER) plays important roles in cell growth, development and
      tumorigenesis. Although ER-regulated genes have been extensively investigated,
      little is known about roles of ER-regulated lncRNAs in breast cancer. Here, we
      conducted genome-wide study of ER-regulated lncRNAs by using RNA-seq, ChIP-seq
      and TCGA data. A total of identified 114 ER-regulated lncRNAs were identified,
      many of them were overexpressed in ER+ breast cancer and co-expressed with some
      key regulators. Silencing one of most prominent lncRNA, AP000439.3, resulted in
      inhibition of cell cycle progression and proliferation. Further study revealed
      AP000439.3 can regulate expression of CCND1 through enhancing estrogen receptor
      induction of CCND1. This finding revealed lncRNAs may serve as important
      effectors of ER in regulation of gene expression and cell phenotype in breast
      cancer.

PMID- 29048637
TI  - Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells.
AB  - NADPH oxidase (NOX) complexes (a family of seven isoforms) drive cellular ROS
      production in patho-logical processes such as cancer. NOX-driven ROS production
      is involved in cell mechanisms from signalling to oxidative stress. Leptin, an
      adipokine overexpressed in obese patients, has been investigated in studies on
      breast carcinogenesis, but its effects on oxidative stress remain largely
      unexplored, especially in breast cancer. The study used three human mammary
      epithelial cell models presenting different neoplastic status (healthy primary
      HMECs, neoplastic MCF-7 cells and neoplastic MDA-MB-231 cells) to determine the
      effects of leptin on short-term ROS production and to characterize the enzymes
      involved. All three cell models significantly expressed NADPH oxidase isoform 5
      (NOX5) in our culture conditions. All models showed induced ROS production
      regardless of leptin concentration (10 ng/ml mimicking good health, 100 ng/ml
      mimicking obesity). Cell treatment with either siRNA against NOX5, NOX inhibitor
      DPI or a calcium channel blocker (verapamil) confirmed the putative involvement
      of the NOX5 isoenzyme in ROS production. Moreover, cell treatments suppressed ROS
      production under leptin at both concentrations. Neoplastic cells appeared unable
      to downregulate NOX5 mRNA expression under leptin. Leptin emerged as a potential
      activator of ROS production in human epithelial mammary cells, where the ROS
      production was apparently linked to NOX5 activation. This novel finding could
      shed light on the potential role of obesity-associated hyperleptinemia in mammary
      cells via the activation of NOX enzymes.

PMID- 29048638
TI  - Reversal effect of adenovirus-mediated human interleukin 24 transfection on the
      cisplatin resistance of A549/DDP lung cancer cells.
AB  - Interleukin-24 (IL-24) is a tumor-suppressor gene that has been documented in
      human melanoma cells. IL-24 has marked antitumor activities on various types of
      human cancer, but its underlying mechanism remains unclear. In the present, we
      investigated the effects of human IL-24 (hIL-24) on the chemotherapy resistance
      of lung cancer cells. The cisplatin (DDP)-resistant lung carcinoma cell line
      A549/DDP was subjected to adenovirus-mediated transfection with the human IL-24
      gene (Ad-hIL-24). The growth-inhibitory and apoptotic effects of Ad-hIL-24 on
      A549/DDP cells were observed, and the expression levels of AKT, phosphorylated
      AKT (p-AKT) and P-glycoprotein (P-gp) were detected. Ad-hIL-24 significantly
      decreased the levels of p-AKT and P-gp, and effectively inhibited A549/DDP cell
      growth. Furthermore, A549/DDP cells exhibited a significantly increased rate of
      apoptosis, as well as G2/M-phase arrest, following transfection with Ad-hIL-24,
      and these effects were increased in cells treated with Ad-IL-24 combined with DDP
      when compared with those treated with Ad-hIL-24 or DDP alone. These results
      suggest that hIL-24 can reverse the DDP resistance of lung cancer cells, and that
      the associated mechanism involves the induction of apoptosis and G2/M-phase
      arrest through the phosphoinositide3-kinase (PI3K)/AKT signaling pathway, as well
      as a decrease in drug resistance through P-gp expression.

PMID- 29048640
TI  - DAL-1 attenuates epithelial to mesenchymal transition and metastasis by
      suppressing HSPA5 expression in non-small cell lung cancer.
AB  - Metastasis is the primary cause of death in lung cancer patients and EMT
      (epithelial-mesenchymal transition) promotes metastasis. Previous study revealed
      that DAL-1 (differentially expressed in adenocarcinoma of the lung) could
      attenuate EMT and metastasis in non-small cell lung cancer (NSCLC). Further study
      proved that HSPA5 (heat shock protein 5), which has a promoting effect on EMT,
      could bind to DAL-1. In this study, the mRNA and protein expression levels of
      target molecules were detected by RTq-PCR and western blot assays, the migration
      and invasion abilities were examined by Transwell migration and invasion assay,
      and the proliferation ability was measured by CCK-8 assay. We revealed that DAL-1
      was downregulated while HSPA5 was upregulated in NSCLC and found the protein of
      DAL-1 and HSPA5 co-localized in the cytoplasm and nucleus. We demonstrated that
      DAL-1 can suppress the expression of HSPA5 on mRNA and protein levels, and
      decrease EMT, migration, invasion and proliferation abilities by down-regulating
      HSPA5. Furthermore, we discovered that DAL-1 plays a role in inhibiting
      PI3K/Akt/Mdm2 signaling pathway by suppressing HSPA5.

PMID- 29048639
TI  - Phenotype characterization of human melanoma cells resistant to dabrafenib.
AB  - In the present study, the phenotype of melanoma cells resistant to dabrafenib (a
      B-RAF inhibitor) was investigated, to shed more light on melanoma resistance to B
      RAF inhibition. Melanoma cells resistant to dabrafenib were generated using 3
      different cell lines, A375, 397 and 624.38, all carrying B-RAFV600E, and they
      were characterized by cytofluorometric analysis, Ion Torrent technology,
      immunofluorescence and biochemistry. All dabrafenib-resistant cells showed, in
      addition to a re-activation of MAPK signaling, morphological changes compared to
      their sensitive counterparts, accompanied by an increase in CD90 (mesenchymal
      marker) expression and a decrease in E-cadherin (epithelial marker) expression,
      suggesting an epithelial-to-mesenchymal-like phenotypic transition. However,
      melanoma cells with TGF-beta1-induced epithelial-to-mesenchymal transition (EMT)
      were more sensitive to dabrafenib treatment compared to the sensitivity noted in
      the non-TGF-beta1-induced EMT melanoma cells, suggesting that TGF-beta1-induced
      EMT was not associated with dabrafenib resistance. Although dabrafenib-resistant
      cells exhibited increased cell motility and E-cadherin/vimentin reorganization,
      as expected in EMT, all of them showed unvaried E-cadherin mRNA and unchanged
      Snail protein levels, while Twist1 protein expression was decreased with the
      exception of A375 dabrafenib-resistant melanoma cells, where it was unaffected.
      These findings suggest a distinct active EMT-like process adopted by melanoma
      cells under drug exposure. Furthermore, dabrafenib-resistant cells exhibited stem
      cell-like features, with Oct4 translocation from the cytoplasm to peri-nuclear
      sites and nuclei, and increased CD20 expression. In conclusion, our data, in
      addition to confirming that resistance to dabrafenib is dependent on re
      activation of MAPK signaling, suggest that this resistance is linked to a
      distinct active EMT-like process as well as stem-cell features adopted by
      melanoma cells.

PMID- 29048641
TI  - Baicalein inhibits tumor progression by inhibiting tumor cell growth and tumor
      angiogenesis.
AB  - Baicalein, a herbal medicine, is a natural flavonoid isolated from the roots of
      Scutellaria baicalensis Georgi. It is known for its anticancer, anti-inflammatory
      and neuroprotective properties. Despite these well-known properties, it is not
      yet clear what effect baicalein has on tumor progression. Therefore, in the
      present study, we used B16F10 cells, Lewis lung carcinoma (LLC) cells, and human
      umbilical vein endothelial cells (HUVECs) to investigate the effect of baicalein
      on cell proliferation and viability, migration and tube formation in vitro. In
      addition, an experimental animal model was used to observe the growth rate and
      metastasis of tumors and tumor vessel formation in vivo. Our results showed that
      baicalein decreased the proliferation and migration and induced tumor cell death
      via caspase-3 activation in the B16F10 and LLC cells, and strongly inhibited tube
      formation and cell migration in HUVECs. Furthermore, mouse models showed that
      baicalein reduced the tumor volume and greatly reduced the tumor growth rate in
      the early stages of tumor progression, and the baicalein-treated groups had
      significantly reduced expression of CD31 (endothelial cell marker) and alpha-SMA
      (mural cell marker) in the tumors, indicating that baicalein inhibits tumor
      angiogenesis by disrupting tumor vasculature development. Comparison of the lymph
      node and lung samples collected from the baicalein-treated group, and the
      untreated group showed that baicalein reduced metastasis of the tumor to these
      tissues. In summary, baicalein reduced tumor progression and metastasis, directly
      induced tumor cell death, and inhibited tumor angiogenesis. Our results strongly
      demonstrate that baicalein is a potential chemotherapeutic agent.

PMID- 29048642
TI  - The epigenetic effect of microRNA in BCR-ABL1-positive microvesicles during the
      transformation of normal hematopoietic transplants.
AB  - Epigenetics have been demonstrated to play a pivotal role in the progression of
      multiple cancers. Our previous study has demonstrated that microvesicles (MVs)
      derived from K562 cells could malignantly transform normal hematopoietic cells.
      The aim of this section was to elucidate the epigenetic effects of RNA in K562
      MVs. We altered some epigenetic RNAs (miR-106a-5p, miR-106b-5p and lincPOU3F3) in
      K562-MVs and followed the process of transformation. Global DNA methylation and
      DNA methyltransferase (DNMT) levels were observed respectively. Our findings
      revealed that increased miR-106a/b in K562-MVs accelerated the transformation
      process (8.33+/-0.94 vs. 13.29+/-1.28 days; P<0.01) whereas decreased lincPOU3F3
      delayed the transformation (17.83+/-0.29 days; P<0.05). The targets of miR-106a/b
      and lincPOU3F3 in the recipient cells were DNMT3a and DNMT3b. We found that
      lincPOU3F3 directly increased the DNMT3a/b while miR-106a/b only in part by
      targeting RB. However, global DNA methylation and special gene methylation was
      altered due to the concurrent regulation of DNMT3a and DNMT3b. Consequently, we
      demonstrated that tumor-derived MVs represent a notable intercellular epigenetic
      communication between cancer cells and recipient cells.

PMID- 29048643
TI  - Novel transduction of nutrient stress to Notch pathway by RasGRP3 promotes
      malignant aggressiveness in human esophageal squamous cell carcinoma.
AB  - In the process of enlarging of tumors, the dissolving tissue structures and
      remodeling endothelial cells for restoring gas exchange and nutritional support,
      further facilitate tumor cell invasion and metastasis. Activation of Ras plays a
      critical role in the development of esophageal squamous cell carcinoma (ESCC),
      but the underlying mechanisms remain poorly understood. We therefore investigated
      whether Ras guanyl-releasing protein 3 (RasGRP3), a Ras activator, could promote
      metastasis by inducing vascular regeneration and further epithelial-mesenchymal
      transition under nutrient stress (NS). In the present study, we explored that the
      accumulation of RasGRP3 regulated vascular endothelial growth factor-A
      production, co-stimulated Notch pathway with high expression of Notch
      intracellular domain (NICD) and Hes1. Moreover, ESCC cells under NS increased the
      expression of vimentin, Snail, Slug and MMP9 proteins; while inhibition of Notch
      activation by DAPT (a gamma-secretase inhibitor) or RasGRP3-targeted RNA
      interference prevented from the effect. In conclusion, these findings provide a
      new insight into the upregulation of RasGRP3 involved in Notch pathway activation
      in the development of ESCC, especially under nutrient deprivation.

PMID- 29048644
TI  - Human amniotic epithelial cells inhibit growth of epithelial ovarian cancer cells
      via TGF-beta1-mediated cell cycle arrest.
AB  - It is reported that human amniotic epithelial cells (hAECs) endow intrinsic
      antitumor effects on certain kinds of cancer. This research was designed to
      evaluate whether hAECs endowed potential anticancer properties on epithelial
      ovarian cancer (EOC) cells in vivo and in vitro, which has not been reported
      before. In this study, we established a xenografted BALB/c nude mouse model by
      subcutaneously co-injecting ovarian cancer cell line, SK-OV-3, and hAECs for 28
      days. In ex vivo experiments, CCK-8 cell viability assay, real-time PCR, cell
      counting assay, cell cycle analysis and immunohistochemistry (IHC) assay were
      used to detect the effects of hAEC-secreted factors on the proliferation and cell
      cycle progression of EOC cells. A cytokine array was conducted to detect
      anticancer-related cytokines released from hAECs. Human recombinant TGF-beta1 and
      TGF-beta1 antibody were used to treat EOC cells and analyzed whether TGF-beta1
      contributed to the cell cycle arrest. Results from in vivo and ex vivo
      experiments showed that hAEC-secreted factors and rhTGF-beta1 decreased
      proliferation of EOC cells and induced G0/G1 cell cycle arrest in cancer cells,
      which could be partially reversed by excess TGF-beta1 antibody. These data
      indicate that hAECs endow potential anticancer properties on epithelial ovarian
      cancer in vivo and in vitro which is partially mediated by hAEC-secreted TGF
      beta1-induced cell cycle arrest. This study suggests a potential application of
      hAEC-based therapy against epithelial ovarian cancer.

PMID- 29048645
TI  - Establishment and characterization of human osteosarcoma cells resistant to
      pyropheophorbide-alpha methyl ester-mediated photodynamic therapy.
AB  - The present study was performed to establish and characterize new human
      osteosarcoma cell lines resistant to pyropheophorbide-alpha methyl ester-mediated
      photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the
      human osteosarcoma MG63 and HOS cell lines and two resistant populations were
      finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8)
      assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and
      proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells. The intracellular ROS
      were analyzed using DCFH-DA staining. The colony formation, invasion and
      migration of parental and resistant cells were compared. FCM was employed to
      examine the cell cycle distribution, the apoptosis rate and the proportion of
      CD133+ cells. The fluorescence intensity of intracellular MPPa was observed by
      fluorescence microscopy and quantified using microplate reader. The protein
      levels were assessed by western blotting (WB). Compared with two parental cells,
      MG63/PDT and HOS/PDT were 1.67- and 1.61-fold resistant to MPPa-PDT,
      respectively, and also exhibited the resistance to CDDP. FCM assays confirmed
      that both MG63/PDT and HOS/PDT cells treated with MPPa-PDT displayed a
      significantly lower apoptosis rate in comparison with their corresponding
      parental cells. The expression of apoptosis-related proteins (i.e. cleaved
      caspase 3 and cleaved-PARP), intracellular ROS and the antioxidant proteins (HO-1
      and SOD1) in MG63/PDT and HOS/PDT cells was also lower than that in parental
      cells. Both MG63/PDT and HOS/PDT cells exhibited changes in proliferation,
      photosensitizer absorption, colony formation, invasion, migration and the cell
      cycle distribution as compared to MG63 and HOS cells, respectively. Compared to
      MG63 and HOS cells, both resistant cell lines had a higher expression of CD133,
      survivin, Bcl-xL, Bcl-2, MRP1, MDR1 and ABCG2, but a lower expression of Bax. The
      present study successfully established two resistant human osteosarcoma cell
      lines which are valuable to explore the resistance-related mechanisms and the
      approaches to overcome resistance.

PMID- 29048646
TI  - SSRP1 silencing inhibits the proliferation and malignancy of human glioma cells
      via the MAPK signaling pathway.
AB  - Structure-specific recognition protein 1 (SSRP1) has been considered as a
      potential biomarker, since aberrant high expression of SSRP1 has been detected in
      numerous malignant tumors. However, the correlation between the expression level
      of SSRP1 and glioma remains unclear. The present study attempted to investigate
      the role of SSRP1 in the pathogenesis of glioma. In the present study, our data
      revealed that SSRP1 overexpression was detected in glioma tissues at both the
      mRNA and protein levels using quantitative real-time RT-PCR and
      immunohistochemical analysis. We also demonstrated that the upregulated
      expression of SSRP1 was correlated with the World Health Organization (WHO) grade
      of glioma. The knockdown of SSRP1 by siRNA not only resulted in the inhibition of
      cell proliferation, but also significantly inhibited glioma cell migration and
      invasion. Mechanistic analyses revealed that SSRP1 depletion suppressed the
      activity of the phosphorylation of the MAPK signaling pathway. In conclusion, the
      present study indicated that SSRP1 regulated the proliferation and metastasis of
      glioma cells via the MAPK signaling pathway.

PMID- 29048647
TI  - Transdifferentiation of human MNNG/HOS osteosarcoma cells into vascular
      endothelial cells in vitro and in vivo.
AB  - The transdifferentiation of cancer cells into other types of cells in several
      types of tissues or organs has been studied. However, whether human osteosarcoma
      MNNG/HOS cells can transdifferentiate into other types of cells has seldom been
      reported. Meanwhile, the mechanism of tumor angiogenesis is still disputed, and
      whether MNNG/HOS cells participate in angiogenesis in osteosarcoma remains
      unknown. In the present study, the investigation was divided into two parts: in
      vitro and in vivo. In vitro, we cultivated MNNG/HOS cells under hypoxic
      conditions for 4 days and found that they typically showed a characteristic
      'flagstone' appearance as cultured vascular endothelial cells (VECs). MNNG/HOS
      cells that were cultivated on Matrigel under hypoxic conditions gradually formed
      tubular-like structures. Furthermore, when cultured under hypoxic conditions for
      4 days, MNNG/HOS cells also transcribed and expressed several molecular markers
      of VECs (CD31, CD34 and vWF). In vivo, MNNG/HOS cells (1x106 cells) were
      cultivated under hypoxic conditions and subcutaneously injected into nude mice;
      the mice were sacrificed 49 days after inoculation. Immunohistochemical staining
      with anti-human CD31 antibody showed evidence of tumor angiogenesis in human
      osteosarcoma MNNG/HOS cells. The results demonstrated that MNNG/HOS cells can
      transdifferentiate into vascular endothelial cell-like cells in vitro and in
      vivo.

PMID- 29048648
TI  - Long non-coding RNA XIST regulates PDCD4 expression by interacting with miR-21-5p
      and inhibits osteosarcoma cell growth and metastasis.
AB  - lncRNA-X-inactive specific transcript (lncRNA XIST) has been demonstrated to be a
      tumor suppressor involved in the pathogenesis and development of various cancers.
      However, the function of XIST and its working mechanism in osteosarcoma (OS)
      remain enigmatic. Firstly, we determined the expression of XIST in OS tissues and
      cell lines by quantitative reverse transcription-PCR (qRT-PCR) and explored
      whether aberrant XIST expression was associated with recurrence and short overall
      survival. Furthermore, the effects of XIST on osteosarcoma cells were studied by
      lentivirus mediated overexpression approach in vitro and in vivo. Detection of a
      set of epithelial-mesenchymal transition (EMT) markers was performed to explore
      whether XIST is involved in EMT. Finally, we investigated the regulatory
      mechanism of XIST acting as a competitive endogenous RNA (ceRNA) of miR-21-5p in
      OS progression and metastasis. lncRNA XIST was significantly downregulated in
      osteosarcoma tissues and osteosarcoma cells, and associated with recurrence and
      short overall survival in OS patients. XIST overexpression remarkably inhibited
      the proliferation of OS cells as well as the xenograft tumor formation in vivo.
      Both cell invasion and migration were inhibited by XIST overexpression via
      suppressing the EMT process. These results indicated that XIST functioned as a
      tumor suppressor in OS. Moreover, we found that miR-21-5p interacted with XIST by
      directly targeting the miRNA-binding site in the XIST sequence, and qRT-PCR
      results showed XIST and miR-21-5p could affect each other's expression,
      respectively. The following assays verified that the tumor suppressor, PDCD4 was
      a functional target of miR-21-5p in OS cells. Finally, we affirmed that XIST
      regulated PDCD4 expression by competitively binding to miR-21-5p. XIST inhibited
      cell proliferation and cell mobility by competitively binding to miR-21-5p and
      upregulating PDCD4 in OS. Our study demonstrated that lncRNA-XIST, which acts as
      a miRNA sponge, impedes miR-21-5p to maintain the expression of PDCD4, which
      contributes to the progression of OS. Our findings suggest that the newly
      identified XIST/miR-21-5p/PDCD4 axis could be a potential biomarker or
      therapeutic target for OS.

PMID- 29048649
TI  - Paclitaxel-mediated human aryl hydrocarbon receptor mRNA translation by an
      internal ribosomal entry site-dependent mechanism.
AB  - The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      that is best known in mediating the toxicities of dioxins and dioxin-like
      compounds. AHR is activated by a variety of endogenous ligands and participating
      in tumor development. Thus, it will provide a new approach for cancer prevention
      and treatment to study the translation mechanism of AHR in tumor cells. In this
      study, we show that the 5'-untranslated region (UTR) of AHR mRNA contains an
      internal ribosome entry site (IRES). After mapping the entire AHR 5'-UTR, we
      determined that the full-length 5'-UTR is indispensable for the highest IRES
      activity. Interestingly, we found that AHR expression is induced in ovarian
      (A2780), breast (MDA-MB231), hepatic (Bel7402) and colorectal cancer cells
      (SW620) by chemotherapeutic drug paclitaxel (PTX) through IRES-dependent
      translation mechanism. Moreover, IRES activity is increased in the PTX-resistant
      ovarian cancer cells in which AHR protein expression was also enhanced. These
      results strongly suggest an important role for AHR IRES-dependent translation
      mechanism in cancer cell response to paclitaxel treatment.

PMID- 29048650
TI  - Predicting radiotherapy response for patients with soft tissue sarcoma by
      developing a molecular signature.
AB  - Soft tissue sarcomas are rare and aggressive tumors arising from connective
      tissues. Adjuvant radiotherapy is a commonly used treatment approach for the
      majority of sarcomas. We attempted to identify a gene signature that can predict
      radiosensitive patients who are most likely to have a better treatment response
      from radiotherapy, compared with disease progression. Using the publicly
      available data of soft tissue sarcoma from The Cancer Genome Atlas, we developed
      a cross-validation procedure to identify a predictive gene signature for
      radiosensitivity. The results showed that the predicted radiosensitive patients
      who received radiotherapy had significantly improved treatment response. We
      further provide supportive evidence to validate our sensitivity prediction.
      Results showed that the predicted radiosensitive patients who received
      radiotherapy had significantly improved survival than patients who did not. ROC
      analysis showed that the developed gene signature had a powerful prediction on
      treatment response. We further found that predicted radiosensitive patients who
      received radiotherapy had a significantly reduced rate of new tumor events.
      Finally, we validated our gene signature using a hierarchical cluster analysis,
      and found that the predicted sensitivities were well-matched with results from
      the cluster analysis. These results are consistent with our expectation,
      suggesting that the identified gene signature and radiosensitivity prediction are
      effective. The genes involved in the signature may provide a molecular basis for
      prognostic studies and radiotherapy target discovery.

PMID- 29048651
TI  - Inhibitor of beta-catenin and TCF (ICAT) promotes cervical cancer growth and
      metastasis by disrupting E-cadherin/beta-catenin complex.
AB  - The inhibitor of beta-catenin and TCF (ICAT) blocks the binding of TCF to beta
      catenin and has been demonstrated as a suppressor of the Wnt/beta-catenin
      signaling pathway. It has been reported to exert a different function around a
      wide variety of cancers. However, its function and underlying mechanisms in human
      cervical cancer remains unknown. In the present study, the expression of ICAT in
      41 human cervical cancer tissues and 30 normal cervical tissues was evaluated by
      immunohistochemical analysis. ICAT was found highly expressed in cancer tissues.
      ICAT overexpression significantly promoted SiHa cell proliferation in vitro by
      causing G1 arrest, and enhanced cell migration and invasion whereas, ICAT
      knockdown induced opposite effects in Caski cells which have higher expression of
      ICAT. Downregulation or overexpression of ICAT resulted in an altered expression
      of the epithelial-mesenchymal transition (EMT). Furthermore, immunoprecipitation
      assays revealed that ICAT pormoted cervical cancer EMT by competing in E-cadhenin
      binding to beta-caterin. Overexpression of ICAT in SiHa cells promoted tumor
      growth and EMT was also demonstrated by the xenograft mouse experiment. These
      results demonstrate that ICAT contributed to the progression of cervical cancer
      and may play a role in the regulation of EMT by distrupting the E-cadherin/beta
      catenin complex. It may be a novel potential therapeutic target for therapy in
      human cervical cancer.

PMID- 29048652
TI  - Activation of Src signaling mediates acquired resistance to ALK inhibition in
      lung cancer.
AB  - Anaplastic lymphoma kinase (ALK) fusion oncogenes occur in approximately 3-5% of
      non-small cell lung cancer (NSCLC) cases. Various ALK inhibitors are in clinical
      use for the treatment of ALK-NSCLC, including the first generation ALK inhibitor,
      crizotinib, and recently the more highly potent alectinib and ceritinib. However,
      most tumors eventually become resistant to ALK specific inhibitors. To address
      the mechanisms underlying the development of ALK inhibitor resistance, we used
      iTRAQ quantitative mass spectrometry and phosphor-receptor tyrosine kinase arrays
      to investigate intracellular signaling alterations in ALK inhibitor resistant
      NSCLC cell lines. Src signaling was identified as an alectinib resistance
      mechanism, and combination treatment with ALK and Src inhibitors was highly
      effective for inhibiting the growth of ALK inhibitor resistant cells in vitro and
      in mouse xenograft models. Furthermore, phospho-receptor tyrosine kinase
      activation and downstream PI3K/AKT signaling was effectively blocked by
      inhibiting Src in alectinib resistant cells. Finally, we showed that the combined
      use of ALK and Src inhibitors inhibited the growth of other ALK-NSCLC cell lines,
      including those that were ceritinib or lorlatinib resistant. Our data suggest
      that targeting Src signaling may be an effective approach to the treatment of ALK
      NSCLC with acquired resistance to ALK inhibitors.

PMID- 29048653
TI  - Ribosomal protein S3 regulates XIAP expression independently of the NF-kappaB
      pathway in breast cancer cells.
AB  - The X-linked inhibitor of apoptosis (XIAP) confers the resistance of various
      types of cancer to standard chemotherapeutic agents such as anthracycline and
      taxane. In breast cancer, XIAP is known to be overexpressed. However, the
      mechanisms underlying the overexpression of XIAP remain currently unclear. In
      order to elucidate the mechanisms responsible for the overexpression of the XIAP
      protein in breast cancer, we attempted to clarify the mechanisms by which the
      natural compound curcumin downregulates XIAP in breast cancer cells. In that
      process, we identified the ribosomal protein S3 (RPS3) as a curcumin-binding
      protein using curcumin-fixed magnetic FG beads. The knockdown of RPS3 inhibited
      cell growth and induced apoptosis as well as the downregulation of XIAP in breast
      cancer cells. Although RPS3 is known to directly bind to and activate the nuclear
      factor-kappaB (NF-kappaB), which induces several anti-apoptotic genes such as
      XIAP, the knockdown of RPS3 unexpectedly reduced the levels of the XIAP protein,
      but not the mRNA level of XIAP and the transcription factor NF-kappaB activity.
      These results reveal that RPS3 upregulates XIAP independently of the NF-kappaB
      pathway in human breast cancer cells.

PMID- 29048654
TI  - Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by
      inducing cell cycle arrest.
AB  - Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver
      and the third leading cause of cancer-related death. Telmisartan, a widely used
      antihypertensive drug, is an angiotensin II type 1 (AT1) receptor blocker (ARB)
      that might inhibit cancer cell proliferation, but the mechanisms through which
      telmisartan affects various cancers remain unknown. The aim of the present study
      was to evaluate the effects of telmisartan on human HCC and to assess the
      expression of microRNAs (miRNAs). We studied the effects of telmisartan on HCC
      cells using the HLF, HLE, HepG2, HuH-7 and PLC/PRF/5 cell lines. In our
      experiments, telmisartan inhibited the proliferation of HLF, HLE and HepG2 cells,
      which represent poorly differentiated types of HCC cells. However, HuH-7 and
      PLC/PRF/5 cells, which represent well-differentiated types of HCC cells, were not
      sensitive to telmisartan. Telmisartan induced G0/G1 cell cycle arrest of HLF
      cells by inhibiting the G0-to-G1 cell cycle transition. This blockade was
      accompanied by a marked decrease in the levels of cyclin D1, cyclin E and other
      cell cycle-related proteins. Notably, the activity of the AMP-activated protein
      kinase (AMPK) pathway was increased, and the mammalian target of rapamycin (mTOR)
      pathway was inhibited by telmisartan treatment. Additionally, telmisartan
      increased the level of caspase-cleaved cytokeratin 18 (cCK18), partially
      contributed to the induction of apoptosis in HLF cells and reduced the
      phosphorylation of ErbB3 in HLF cells. Furthermore, miRNA expression was markedly
      altered by telmisartan in vitro. In conclusion, telmisartan inhibits human HCC
      cell proliferation by inducing cell cycle arrest.

PMID- 29048655
TI  - PomGnT1 enhances temozolomide resistance by activating epithelial-mesenchymal
      transition signaling in glioblastoma.
AB  - Temozolomide (TMZ) is commonly used in glioblastoma (GBM) chemotherapy. However,
      a great challenge for TMZ treatment is the rapid development of resistance and
      subsequent tumor recurrence and poor outcome. In the present study we established
      TMZ-resistant GBM cells (U87-TR and U251-TR) and found that the expression of
      PomGnT1 was significantly upregulated in TMZ-resistant GBM cells compared with
      the TMZ-sensitive counterparts. Furthermore, overexpression of PomGnT1 in U87-MG
      and U251-MG cells led to increased IC50 values for TMZ and reduced apoptosis of
      cells. Knockdown of PomGnT1 in both U87-TR and U251-TR cells led to decreased
      IC50 values for TMZ and enhanced apoptosis. Biochemical analysis revealed that
      PomGnT1 regulates the expression of factors in epithelial-mesenchymal transition
      signaling including TCF8, vimentin, beta-catenin and Slug in GBM cells. These
      findings demonstrate that PomGnT1 might be a new focus of GBM research for
      treatment of recurrent TMZ-resistant GBM.

PMID- 29048656
TI  - NRG1-dependent activation of HER3 induces primary resistance to trastuzumab in
      HER2-overexpressing breast cancer cells.
AB  - This study was conducted to determine the role of neuregulin 1 (NRG1)-dependent
      human epidermal growth factor receptor 3 (HER3) activation in trastuzumab primary
      resistance, and to observe the inhibitory effect of HER3 monoclonal antibody on
      HER2-overexpressing breast cancer cells. BT474 cells (trastuzumab sensitive) and
      MDA-MB-453 cells (trastuzumab resistant) were first stimulated with NRG1 and then
      treated with either trastuzumab, HER3 antibody, or a combination of both. The
      expression of phospho human epidermal growth factor receptor 2 (p-HER2), phospho
      human epidermal growth factor receptor 3 (p-HER3), phospho protein kinase B (p
      Akt) and phospho mitogen-activated protein kinase (p-MAPK) were detected by
      western blotting. Apoptosis was detected by flow cytometry. Cell viability was
      detected by MTT assay. Without NRG1 stimulation, trastuzumab treatment
      significantly down-regulated the expression of p-HER2, increased early apoptosis,
      and decreased cell viability in BT474 cells. After NRG1 stimulation, the
      aforementioned effects weakened or disappeared in the trastuzumab treatment
      group, whereas in the HER3 antibody treatment group, there was significant
      downregulation in p-HER3 expression and increase in early apoptosis of BT474
      cells. In MDA-MB-453 cells, the HER3 antibody significantly downregulated both p
      HER2 and p-HER3 and promoted early apoptosis after NRG1 stimulation, however,
      trastuzumab hardly played a role. p-Akt and p-MAPK were also significantly
      downregulated by the HER3 antibody after NRG1 stimulation. The expressions of p
      HER2, p-HER3, p-Akt and p-MAPK were all downregulated after HER3 gene silencing,
      compared to the control. NRG1-dependent activation of HER3 induces primary
      resistance to trastuzumab in HER2-overexpressing breast cancer cells. HER3
      monoclonal antibody combined with trastuzumab may serve as a treatment choice for
      patients with primary resistance to trastuzumab.

PMID- 29048657
TI  - Toosendanin suppresses oncogenic phenotypes of human gastric carcinoma SGC-7901
      cells partly via miR-200a-mediated downregulation of beta-catenin pathway.
AB  - Aberrant activation of beta-catenin signaling due to low expression of miR-200a
      is found in gastric carcinoma (GC) tissues promoting GC evolution. Toosendanin
      (TSN) has exhibited antitumor effects on various human cancer cells, but its
      influence on GC is largely unidentified. The potential roles of TSN on GC cells
      were examined and it was found that TSN inhibited growth, migration, invasion and
      TGF-beta1-induced epithelial-mesenchymal transition (EMT) and induced cell cycle
      arrest and apoptosis in SGC-7901 cells which were most sensitive to TSN among
      various GC cell lines. TSN also inactivated beta-catenin pathway in SGC-7901
      cells and the above effects were reversed following induction of beta-catenin
      overexpression. Moreover, TSN facilitated the level of miR-200a which targets
      beta-catenin and miR-200a silencing attenuated the antitumor effects of TSN on
      SGC-7901 cells. Nonetheless, knockdown of miR-200a did not relieve the
      suppressive effects of TSN on p-AKT, p-ERK and p-GSK3beta which were upstream
      regulators of beta-catenin. In addition, TSN administration inhibited growth and
      liver metastasis of orthotopically implanted SGC-7901 tumors in vivo through miR
      200a-mediated beta-catenin pathway. Our data suggest that TSN may suppress
      oncogenic phenotypes of human GC cells partly via miR-200a/beta-catenin axis.
      Hence, TSN may have a promising chemotherapeutic activity for GC therapy.

PMID- 29048658
TI  - Functional diversity of miR-146a-5p and TRAF6 in normal and oral cancer cells.
AB  - Numerous studies implicate miR-146a as pleiotropic regulator of carcinogenesis;
      however, its roles in carcinogenesis are not fully understood. A clue from
      expression analyses of miR-146a-5p in all 13 oral squamous cell carcinoma (OSCC)
      cell lines examined and in OSCC tissues, whole blood and whole saliva of OSCC
      patients in vivo revealed that miR-146a-5p expression was highly upregulated.
      Particularly, we widened the view of its upregulation in saliva, implicating that
      high miR-146a-5p expression is not only correlated closely to the development of
      human oral cancer, but also to a possible candidate as a diagnostic marker of
      OSCC. Indeed, further examination showed that exogenous miR-146a-5p expression
      showed pleiotropic effects on cell proliferation and apoptosis which were
      partially based on the contextual responses of activation of JNK, downstream of
      TRAF6 that was targeted by miR-146a-5p in normal human keratinocytes and OSCC
      cell lines. TRAF6 suppression by a TRAF6-specific siRNA resulted in contradictory
      consequences on cellular processes in normal and OSCC cells. Notably, TRAF6
      downregulation by both miR-146a-5p and TRAF6-specific siRNA deactivated JNK in
      SCC-9, but not in normal human keratinocytes. In support of the proliferation
      promoting effect of miR-146a-5p, silencing of endogenous miR-146a-5p
      significantly reduced proliferation of SCC-9. Together, these results suggest
      that miR-146a-5p affects proliferation and apoptosis in a cellular context
      dependent manner and selectively disarms the TRAF6-mediated branch of the TGF
      beta signaling in OSCC cell lines by sparing Smad4 involvement.

PMID- 29048659
TI  - MicroRNA-520c-3p negatively regulates EMT by targeting IL-8 to suppress the
      invasion and migration of breast cancer.
AB  - Interleukin-8 (IL-8), which is secreted by cancer cells undergoing epithelial
      mesenchymal transition (EMT), can promote EMT in adjacent epithelial-like cells.
      MicroRNAs (miRNAs/miRs) can affect the expression of target genes via binding to
      their 3'-untranslated regions (3'-UTRs), which may subsequently affect the
      biological behaviors of cancer cells. In our previous study, miR-520c-3p was
      predicted to directly target the 3'-UTR of IL-8. Therefore, the present study was
      carried out to investigate whether miR-520c-3p can interact with the IL-8 gene
      and regulate the EMT of breast cancer cells. Web-based prediction algorithms were
      used to identify miRNAs that potentially target the IL-8 transcript. Luciferase
      reporter assays were used to confirm the targeting of IL-8 by miR-520c-3p.
      Reverse transcription-quantitative PCR and western blot analyses were used to
      examine the levels of IL-8 and EMT-related genes in breast cancer cells. The
      functional impact of miR-520c-3p on EMT phenotype was evaluated using Transwell
      and wound-healing assays, and rescue experiments were conducted by overexpressing
      IL-8 to determine its effect on cell properties. miR-520c-3p was predicted by all
      three databases, which strongly suggested its interaction with the 3'-UTR of IL
      8. The relative Renilla luciferase activity of luciferase reporter construct
      containing the wild-type 3'-UTR of IL-8 was markedly decreased by miR-520c-3p
      transfection when compared with scrambled miRNA control transfection (P<0.001).
      In addition, compared with the scrambled miRNA control transfection, the
      overexpression of miR-520c-3p significantly reduced the expression of IL-8, and
      resulted in increased E-cadherin and decreased vimentin and fibronectin levels in
      MCF-7 and T47D cells (all P<0.001). Introduction of miR-520c-3p inhibited the
      invasion and migration of MCF-7 and T47D cells (all P<0.001). By contrast, the
      rescue of IL-8 expression led to the recovery of EMT-related protein expression
      patterns and cell motility and invasion capabilities. In conclusion, aberrant miR
      520c-3p expression may lead to reduced IL-8 expression and promote the
      mesenchymal phenotype in breast cancer cells, thereby increasing invasive growth.

PMID- 29048661
TI  - Combination of FGFR4 inhibitor Blu9931 and 5-fluorouracil effects on the
      biological characteristics of colorectal cancer cells.
AB  - The aim of this study was to explore the effects of single agent treatments and
      combination of Blu9931 and 5-fluorouracil (5-FU) on the biological
      characteristics of colorectal cancer cells and its mechanism. Blu9931 is the
      first selective small molecule inhibitor of the fibroblast growth factor receptor
      4 (FGFR4) and exquisitely selective for FGFR4 versus other FGFR family members
      and all other kinases. The colorectal cancer cells HCT116 and SW620 with high
      expression of FGFR4 were selected for a series of functional tests including cell
      viability, cell proliferation, apoptosis and cell cycle detection. Western
      blotting was used to detect the expression of related molecules including signal
      pathway (STAT3), apoptosis (cleaved caspase-3), cell cycle (cyclin D1 and
      P27kip1) and epithelial-mesenchymal transition (E-cadherin and vimentin) in
      HCT116 and SW620 cells used as single and combination treatments of 5-FU and
      Blu9931. The cell viability gradually decreased when the concentration of 5-FU
      and Blu9931 increased. Blu9931 can inhibit FGFR4 protein expression while 5-FU
      cannot, as assessed by western blot analysis. The single agent treatment and
      combinations of 5-FU and Blu9931 arrest cell cycle (P<0.05), increased p27kip1
      expression and reduced cyclin D1 expression. The single agent treatment and
      combinations of 5-FU and Blu9931 inhibited EMT. Furthermore, the combination of 5
      FU and Blu9931 has a synergistic effect in reducing colorectal cancer cell
      proliferation and preventing cell cycle. Taken together, this study provides the
      first evidence that Blu9931 functions as a FGFR4-selective inhibitor in
      colorectal cancer (CRC) cells, and Blu9931 may be a new targeted drug.

PMID- 29048660
TI  - Canonical and non-canonical WNT signaling in cancer stem cells and their niches:
      Cellular heterogeneity, omics reprogramming, targeted therapy and tumor
      plasticity (Review).
AB  - Cancer stem cells (CSCs), which have the potential for self-renewal,
      differentiation and de-differentiation, undergo epigenetic, epithelial
      mesenchymal, immunological and metabolic reprogramming to adapt to the tumor
      microenvironment and survive host defense or therapeutic insults. Intra-tumor
      heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and
      recurrence through clonal replacement and reactivation of dormant CSCs,
      respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and
      TGFbeta/BMP signaling cascades and regulate expression of functional CSC markers,
      such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49). Aberrant canonical and non
      canonical WNT signaling in human malignancies, including breast, colorectal,
      gastric, lung, ovary, pancreatic, prostate and uterine cancers, leukemia and
      melanoma, are involved in CSC survival, bulk-tumor expansion and
      invasion/metastasis. WNT signaling-targeted therapeutics, such as anti
      FZD1/2/5/7/8 monoclonal antibody (mAb) (vantictumab), anti-LGR5 antibody-drug
      conjugate (ADC) (mAb-mc-vc-PAB-MMAE), anti-PTK7 ADC (PF-06647020), anti-ROR1 mAb
      (cirmtuzumab), anti-RSPO3 mAb (rosmantuzumab), small-molecule porcupine
      inhibitors (ETC-159, WNT-C59 and WNT974), tankyrase inhibitors (AZ1366, G007-LK,
      NVP-TNKS656 and XAV939) and beta-catenin inhibitors (BC2059, CWP232228, ICG-001
      and PRI-724), are in clinical trials or preclinical studies for the treatment of
      patients with WNT-driven cancers. WNT signaling-targeted therapeutics are
      applicable for combination therapy with BCR-ABL, EGFR, FLT3, KIT or RET
      inhibitors to treat a subset of tyrosine kinase-driven cancers because WNT and
      tyrosine kinase signaling cascades converge to beta-catenin for the maintenance
      and expansion of CSCs. WNT signaling-targeted therapeutics might also be
      applicable for combination therapy with immune checkpoint blockers, such as
      atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab and pembrolizumab, to
      treat cancers with immune evasion, although the context-dependent effects of WNT
      signaling on immunity should be carefully assessed. Omics monitoring, such as
      genome sequencing and transcriptome tests, immunohistochemical analyses on PD-L1
      (CD274), PD-1 (PDCD1), ROR1 and nuclear beta-catenin and organoid-based drug
      screening, is necessary to determine the appropriate WNT signaling-targeted
      therapeutics for cancer patients.

PMID- 29048662
TI  - Capsaicin inhibits proliferation and induces apoptosis in osteosarcoma cell lines
      via the mitogen-activated protein kinase pathway.
AB  - Capsaicin, a pungent molecular compound present in many hot peppers, exerts
      anticancer activities against various human cancer cell lines by inducing
      apoptosis. However, the effects of capsaicin on human osteosarcoma (OS) as well
      as the related mechanisms remain to be fully elucidated. In the present study,
      the anticancer effects of capsaicin on 3 human OS cell lines (MG63, 143B and HOS)
      were investigated. Various concentrations of capsaicin (50-300 uM) effectively
      decreased cell viability in all 3 OS cell lines in a dose-dependent manner.
      Notably, capsaicin-induced apoptosis was observed when OS cells were treated with
      relatively high concentrations of capsaicin (starting at 250 uM). In addition,
      the mitochondrial apoptotic pathway was involved in the capsaicin-induced
      apoptosis in the OS cells. Meanwhile, our results also indicated that at
      relatively low concentrations (e.g., 100 uM), capsaicin could inhibit the
      proliferation, decrease the colony forming ability and induce G0/G1 phase cell
      cycle arrest of OS cells in a dose-dependent manner. Moreover, our results
      revealed that the anticancer effects induced by capsaicin on OS cell lines
      involved multiple MAPK signaling pathways as indicated by inactivation of the
      ERK1/2 and p38 pathways and activation of the JNK pathway. Furthermore, the
      results of animal experiments showed that capsaicin inhibited tumor growth in a
      xenograft model of human OS. In conclusion, these results indicate that capsaicin
      may exert therapeutic benefits as an adjunct to current cancer therapies but not
      as an independent anticancer agent.

PMID- 29048663
TI  - Suppression of LETM1 by siRNA inhibits cell proliferation and invasion of bladder
      cancer cells.
AB  - The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is highly
      expressed in many human malignancies and is correlated with poor prognosis.
      However, the function of LETM1 in bladder cancer still remains unknown. In the
      present study, we analyzed the expression levels of LETM1 in bladder cancer
      tissues and non-cancerous tissues as well as in four bladder cancer cell lines
      (T24, EJ, 5637 and J82) and a human bladder epithelial immortalized cell line SV
      HUC-1. Small interfering RNA (siRNA) was employed to knockdown the expression of
      LETM1 in the T24 cells. The proliferation of T24 cells was significantly
      repressed as evaluated by CCK-8 assays. Transwell migration and invasion assays
      indicated that knockdown of LETM1 suppressed cell migration and invasion
      significantly. Flow cytometric analysis revealed that cells had accumulated at
      the S-phase when the expression of LETM1 was suppressed. Moreover, we found that
      several oncogenic proteins in the Wnt/beta-catenin signaling pathway, namely beta
      catenin, cyclin D1 and c-Myc were significantly decreased by the LETM1 siRNA.
      Collectively, these results revealed that the knockdown of LETM1 exhibited tumor
      suppressive effects, possibly by controlling the downstream Wnt/beta-catenin
      signaling pathway.

PMID- 29048664
TI  - miR-25 promotes metastasis via targeting FBXW7 in esophageal squamous cell
      carcinoma.
AB  - Increasing evidence suggests that miR-25 can function as an oncogene in different
      types of human malignancies, whereas little is known concerning the role of miR
      25 in esophageal squamous cell carcinoma (ESCC). The aim of the present study was
      to investigate the role of miR-25 in ESCC and to determine the molecular
      mechanisms underlying its function. The expression level of miR-25 was detected
      in primary ESCC tissues and cell lines by real-time quantitative PCR. We also
      assessed whether knockdown of miR-25 influences in vitro cell invasion and
      migration. Western blot analysis was used to detect the influence of miR-25 on a
      target gene, and Pearson analysis was used to calculate the correlation between
      the expression of a target gene and miR-25 in ESCC tissues. The results revealed
      that the relative level of miR-25 expression was significantly upregulated in
      ESCC tissues and cell lines. Expression of miR-25 in ESCC tissues was positively
      associated with depth of tumor invasion and tumor stage. Moreover, high miR-25
      expression conferred poorer overall survival (OS), and a multivariate analysis
      revealed that miR-25 was an independent risk factor for OS. In addition,
      knockdown of miR-25 in ESCC cells significantly suppressed cell migration and
      invasion. Furthermore, we identified F-box and WD repeat domain-containing 7
      (FBXW7) protein as a direct functional target of miR-25 in ESCC. In conclusion,
      the present study supports the potential of miR-25 as a prognostic predictor with
      its high expression in cancer tissues and its association with tumor progression
      by targeting FBXW7 in ESCC.

PMID- 29048665
TI  - TGX-221 inhibits proliferation and induces apoptosis in human glioblastoma cells.
AB  - Glioblastoma is the most common type of primary brain tumor in adults, with high
      mortality and morbidity rates. More effective therapeutic strategies are
      imperative. Previous studies have shown that the known p110-beta-selective
      inhibitor TGX-221 blocks the activation of PKB/Akt in PTEN-deficient cells. We
      treated U87 and U251 glioblastoma cells with TGX-221 to determine the effect of
      TGX-221. We performed a Cell Counting Kit-8 (CCK-8) test, EDU staining and cell
      cycle distribution analysis and found that TGX-221 inhibited glioblastoma cell
      proliferation. Next, the effect of TGX-221 on cell apoptosis was investigated
      using flow cytometry. These results demonstrated that TGX-221 induced apoptosis
      in glioblastoma cells. Moreover, migration and invasion assays revealed that TGX
      221 inhibited human glioblastoma cell migration and invasion. Collectively, our
      study revealed that TGX-221 could inhibit proliferation and induce apoptosis in
      glioblastoma cells.

PMID- 29048666
TI  - Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor
      and a COX-2 inhibitor through activation of PTEN.
AB  - Chemotherapy is one of the most effective non-surgical treatments for various
      types of tumor. Identifying different combinations of antitumor agents that can
      produce synergistic antitumor effects remains an important clinical strategy. In
      the present study, we showed that the combination of histone deacetylase 6
      (HDAC6) inhibitor tubastatin A together with cyclooxygenase-2 (COX-2) inhibitor
      celecoxib resulted in synergistic antitumor effects in CAL 27 and SACC-83 cells.
      Treatment with celecoxib alone promoted the membrane translocation of phosphatase
      and tensin homolog (PTEN), indicating PTEN activation, and consequently led to
      protein kinase B (AKT) dephosphorylation (inactivation). Similarly, treatment
      with an HDAC6 inhibitor alone promoted PTEN membrane translocation and
      correspondingly dephosphorylated AKT. The combination of celecoxib and an HDAC6
      inhibitor synergistically increased PTEN membrane translocation and inactivated
      AKT. Moreover, celecoxib enhanced the HDAC6 inhibitor-induced antitumor effects
      in PTEN-deficient U-87 MG cells that had been stably transfected with wild-type
      PTEN, but not in the same cell line stably transfected with mutant PTEN-K163R,
      which cannot be activated by HDAC6 inhibitors. In summary, the results indicated
      that the COX-2 inhibitor celecoxib enhanced the HDAC6 inhibitor-induced antitumor
      effects by activating the PTEN/AKT signaling pathway.

PMID- 29048668
TI  - Celastrol downregulates E2F1 to induce growth inhibitory effects in
      hepatocellular carcinoma HepG2 cells.
AB  - Celastrol, a natural compound extracted from Tripterygium wilfordii, is known to
      exhibit potential anticancer activities in various types of tumor cells. E2F1 is
      reported to be overexpressed in several types of human tumors and its
      inactivation may be a valuable novel potential therapeutic strategy for cancer
      treatment. However, the molecular mechanism underlying the pro-apoptotic effects
      of celastrol on hepatocellular carcinoma (HCC) cells remains unclear, and E2F1
      targeted compounds have been rarely identified. In the present study, we
      demonstrated that celastrol inhibited the proliferation of human HCC cells and
      triggered apoptosis of HepG2 cells in a caspase-dependent manner. E2F1 was
      potently downregulated by celastrol in a dose- and time-dependent manner at both
      the mRNA and protein levels. Moreover, siRNA-mediated E2F1 silencing enhanced
      celastrol-induced apoptosis and inhibition of proliferation. Our data imply that
      downregulation of E2F1 may be a key factor in the celastrol-mediated inhibitory
      effects in HepG2 cells, and celastrol can serve as a leading compound for the
      development of compounds designed to inactivate E2F1 for HCC therapy.

PMID- 29048667
TI  - Inhibitory effect of black tea pigments, theaflavin-3/3'-gallate against
      cisplatin-resistant ovarian cancer cells by inducing apoptosis and G1 cell cycle
      arrest.
AB  - Adverse side effects and acquired resistance to conventional chemotherapy based
      on platinum drive the exploration of other selective anticancer drugs. Theaflavin
      3-gallate (TF2a) and theaflavin-3'-gallate (TF2b), theaflavin monomers in black
      tea, exhibited a potent growth inhibitory effect on cisplatin-resistant ovarian
      cancer A2780/CP70 cells and were less cytotoxic to normal ovarian IOSE-364 cell
      line. Flow cytometry analysis and western blotting indicated that TF2a and TF2b
      induced apoptosis and G1 cell cycle arrest in ovarian cancer A2780/CP70 cells.
      Hoechst 33342 staining was used to confirm the apoptotic effect. Downregulation
      of CDK2 and CDK4 for TF2a and CDK2 and cyclin E1 for TF2b led to the accumulation
      of cells in G1 phase. TF2a and TF2b induced apoptosis and G1 through p53
      dependent pathways. TF2a and TF2b induced DNA damage through ATM/Chk/p53 pathway.
      TF2a and TF2b also induced inhibition of A2780/CP70 cells through Akt and MAPK
      pathways. The results of this study implied that TF2a and TF2b might help prevent
      and treat platinum-resistant ovarian cancer.

PMID- 29048669
TI  - MicroRNA-337 inhibits colorectal cancer progression by directly targeting KRAS
      and suppressing the AKT and ERK pathways.
AB  - Colorectal cancer (CRC) is the third most common cancer and the fourth most
      common cause of cancer-related death worldwide. Tumour progression and
      development in CRC is a multi-step process involving a large number of genetic
      and epigenetic alterations. Previous studies indicated that abnormally expressed
      microRNAs play critical roles in CRC through regulation of oncogenic and tumour
      suppressor genes. Hence, determination of the function of microRNAs may provide
      novel therapeutic targets for CRC diagnosis and treatments. MicroRNA-337 (miR
      337) has been reported to be downregulated in several cancer types. However, the
      expression, function and underlying mechanisms of miR-337 in CRC have not been
      clearly elucidated. In this study, miR-337 was significantly decreased in CRC
      tissues and cell lines. Low miR-337 expression level was correlated with lymph
      node metastasis, distant metastasis and TNM stage of CRC patients. In addition,
      upregulation of miR-337 suppressed cell proliferation and invasion and promoted
      apoptosis in CRC. Based on bioinformatics analysis, we assumed that Kirsten rat
      sarcoma viral oncogene homolog (KRAS) was directly modulated by miR-337 in CRC.
      Luciferase reporter assay demonstrated the direct interaction between miR-337 and
      3'-UTR of KRAS mRNA. Furthermore, reverse transcription-quantitative polymerase
      chain reaction and western blot analysis indicated that miR-337 could negatively
      regulate endogenous KRAS expression in CRC cells at both mRNA and protein levels.
      Moreover, KRAS was highly expressed in CRC tissues and inversely correlated with
      miR-337 expression in CRC tissues. KRAS knockdown recapitulates effects similar
      to those induced by miR-337 overexpression in CRC cells, whereas KRAS
      overexpression partially restored the tumour suppressive effects of miR-337.
      Besides, ectopic expression of miR-337 inactivates the AKT and ERK signalling
      pathways in CRC. These results suggested that miR-337 may act as a tumour
      suppressor during the process of CRC malignant transformation by interacting with
      KRAS.

PMID- 29048670
TI  - Suppression of tumor-derived Semaphorin 7A and genetic ablation of host-derived
      Semaphorin 7A impairs tumor progression in a murine model of advanced breast
      carcinoma.
AB  - Solid tumors can generate a plethora of neurogenesis-related molecules that
      enhance their growth and metastasis. Among them, we have identified axonal
      guidance molecule Semaphorin 7A (SEMA7A) in breast cancer. The goal of this study
      was to determine the therapeutic effect of suppressing SEMA7A levels in the 4T1
      murine model of advanced breast carcinoma. We used anti-SEMA7A short hairpin RNA
      (shRNA) to gene silence SEMA7A in 4T1 mammary tumor cells. When implanted into
      the mammary fat pads of syngeneic mice, SEMA7A shRNA-expressing 4T1 tumors
      exhibited decreased growth rates, deferred metastasis and reduced mortality. In
      vitro, SEMA7A shRNA-expressing 4T1 cells had weakened proliferative, migratory
      and invasive abilities, and decreased levels of mesenchymal factors. Atomic force
      microscopy studies showed that SEMA7A shRNA-expressing 4T1 cells had an increase
      in cell stiffness that corresponded with their decreased malignant potential.
      Genetic ablation of host-derived SEMA7A further enhanced the antitumor effects of
      SEMA7A shRNA gene silencing in 4T1 cells. Our preclinical findings demonstrate a
      critical role for SEMA7A in mediating mammary tumor progression.

PMID- 29048671
TI  - Adoptive immunotherapy combined with FP treatment for head and neck cancer: An in
      vitro study.
AB  - FP treatment, which combines 5-fluorouracil (5-FU) and cisplatin (CDDP)
      chemotherapy, is widely used for treatment of advanced head and neck cancer
      (HNC). It has been suggested that these drugs cause immunomodulation in the
      cancer microenvironment, for example, downregulation of immunosuppressive cells
      such as regulatory T-cells (Tregs) and myeloid-derived suppressive cells (MDSCs),
      activating dendritic cells (DCs), and upregulation of tumor antigens and major
      histocompatibility complex (MHC) molecules in cancer cells leads to enhancement
      of cancer immunity, which is important in cancer treatment, as well as providing
      a direct killing effect. Therefore, development of chemoimmunotherapy by
      combining FP treatment with immunotherapy for HNC has become a recent challenging
      issue. However, the direct effects of these drugs on immune effector cells,
      especially cytotoxic T-lymphocytes (CTLs), are not well known. We have
      investigated the direct actions of these drugs on CTL functions in in vitro
      experiments using cytomegalovirus (CMV) pp65 antigen-specific CTLs (CMVpp65-CTLs)
      and oral squamous cell cancer (OSCC) cell lines overexpressing CMVpp65 antigen as
      target cells. Although CDDP partially inhibited proliferation of memory CMVpp65
      CTL in peripheral blood, the proliferation was not inhibited by 5-FU.
      Cytotoxicity and the IFN-gamma release response of the CMVpp65-CTLs were not
      inhibited by these drugs, and it is important to note that these drugs,
      especially 5-FU, sensitized OSCC cell lines to CMVpp65-CTL. Furthermore, CMVpp65
      CTL cytotoxicity to CDDP-resistant OSCC cells, HSC-3/CDDP-R1, was the same as the
      cytotoxicity to the parental cells. Thus, we suggest that combined immunotherapy
      with FP treatment is an effective novel HNC treatment.

PMID- 29048672
TI  - De novo synthesis of C4.4A in hepatocellular carcinoma promotes migration and
      invasion of tumor cells.
AB  - C4.4A is a glycoprotein that is upregulated in several human malignancies,
      including colorectal, breast and renal cell carcinomas. Due to its highly
      restricted expression in healthy tissue, C4.4A was proposed as a potential
      diagnostic marker. Thus, the present study was designed to evaluate C4.4A
      expression and function in hepatocellular carcinoma (HCC) for the first time.
      Immunohistochemistry was performed to detect expression of C4.4A in human
      sections of healthy liver, primary HCC in the liver and metastatic HCC in the
      lung. To assess the contribution of C4.4A to HCC progression proliferation,
      apoptosis, migration and invasion assays were performed with C4.4A knockdown Huh7
      and HepG2 cells. C4.4A is absent in healthy liver tissue. However, intense
      expression was seen in 59% of primary HCCs and strong expression in 80% of HCC
      lung metastases. C4.4A expression was also observed in human HCC cell lines,
      which strongly increased under hypoxic conditions. A C4.4A knock-down revealed
      that C4.4A is involved in both migration and invasion of HCC cells. Taken
      together, C4.4A expression in both primary and metastatic HCC suggests its
      potential value as a diagnostic marker for HCC. Due to its absence in healthy
      liver tissue, C4.4A might even serve as a possible therapeutic target,
      particularly for metastatic HCC.

PMID- 29048673
TI  - The ethanol extracts of sporoderm-broken spores of Ganoderma lucidum inhibit
      colorectal cancer in vitro and in vivo.
AB  - The medicinal mushroom Ganoderma lucidum (G. lucidum) has been reported to
      possess a variety of pharmacological activities including anticancer effects.
      However, the anti-colorectal cancer effects and the potential molecular
      mechanisms of the ethanol extracts of sporoderm-broken spores of G. lucidum
      (BSGLEE), which mainly contains triterpenoids, have not been reported. The aim of
      the present study was to investigate the anticancer effects and molecular
      mechanisms exerted by BSGLEE on colorectal cancer in vitro and in vivo. MTT assay
      revealed that BSGLEE at 1.6 to 10 mg/ml significantly inhibited HCT116 cell
      proliferation in a dose- and time-dependent manner. Flow cytometric analysis
      demonstrated that BSGLEE induces apoptosis and cell cycle arrest at G0/G1 phase,
      which are associated with deregulation of the expression of key genes and
      proteins (p21, p16, cyclin D1, Bcl-2, bax, NAG-1, PARP and caspase-3) that
      regulate apoptosis and cell cycle cascades. Moreover, BSGLEE significantly
      inhibited HCT116 cell migration via downregulating MMP-1, MMP-2 and upregulating
      E-cadherin expression at mRNA levels. Oral gavage of 75 and 150 mg/kg BSGLEE
      significantly inhibited HCT116 xenograft tumor growth in nude mice, which was
      accompanied by suppressed Ki-67 staining as determined by immunochemistry.
      Collectively, we found that BSGLEE effectively inhibits colorectal cancer
      carcinogenesis through induction of apoptosis, inhibition of migration and
      promotion of cell cycle arrest. Our results suggest that triterpenoids of
      sporoderm-broken spores of G. lucidum ethanol extracts may serve as a promising
      anticancer agent for colorectal cancer chemoprevention and therapy.

PMID- 29048674
TI  - MicroRNA-345 inhibits metastasis and epithelial-mesenchymal transition of gastric
      cancer by targeting FOXQ1.
AB  - MicroRNAs (miRNAs) are a group of critical players in gastric cancer (GC). Among
      numerous cancer-related miRNAs, the expression level and functional role of miR
      345 in GC has not been investigated. This study showed that miR-345 expression
      was decreased in GC. Decreased expression level of miR-345 was associated with
      occurrence of lymph metastasis and advanced TNM stage of GC patients. Patients
      with low expression level of miR-345 had reduced overall survival (OS) and
      disease-free survival (DFS). In vitro experiments showed that miR-345 could
      inhibit the migration and invasion of GC cells. In vivo experiments showed that
      miR-345 knockdown could promote lung metastasis of GC cells in nude mice. miR-345
      was found to prevent the metastasis by inhibiting epithelial-mesenchymal
      transition (EMT) of GC cells. Furthermore, FOXQ1 was confirmed to be the
      downstream target of miR-345 in GC cells. Forced expression of FOXQ1 could
      reverse the inhibitory effects of miR-345 on GC metastasis, while knockdown of
      FOXQ1 prevented the promoting effects of miR-345 knockdown on GC metastasis. In
      summary, this study demonstrates miR-345 is a promising biomarker and therapeutic
      target in GC.

PMID- 29048675
TI  - Naringenin inhibits alcoholic injury by improving lipid metabolism and reducing
      apoptosis in zebrafish larvae.
AB  - Alcoholic liver disease (ALD) includes a spectrum of hepatic abnormalities that
      range from isolated alcoholic steatosis to steatohepatitis and cirrhosis.
      Naringenin, a predominant flavanone in grapefruit, increases resistance to
      oxidative stress and inflammation and protects against multiple organ injury in
      various animal models. However, the specific mechanisms responsible for
      protection against alcoholic injury are poorly understood. In the present study,
      we aimed to investigate the effect of naringenin on alcoholic events and the
      molecular regulatory mechanisms of naringenin in the liver and whole body of
      zebrafish larvae following exposure to 350 mmol/l ethanol for 32 h. Zebrafish
      larvae {4 days post-fertilization (dpf); wild-type (WT) and a transgenic line
      with liver-specific eGFP expression [Tg(lfabp10alpha-eGFP)]} were used to
      establish an alcoholic fatty liver model in order to evaluate the effects of
      naringenin treatment on anti-alcoholic injury. Naringenin significantly reduced
      alcoholic liver morphological phenotypes and the expression of alcohol and lipid
      metabolism-related genes, including cyp2y3, cyp3a65, hmgcra, hmgcrb, fasn,
      fabp10alpha, fads2 and echs1, in zebrafish larvae. Naringenin also attenuated
      hepatic apoptosis in larvae as detected by TUNEL staining, consistent with the
      expression of critical biomarkers of endoplasmic reticulum stress and of DNA
      damage genes (chop, gadd45alphaa and edem1). The present study showed that
      naringenin inhibited alcohol-induced liver steatosis and injury in zebrafish
      larvae by reducing apoptosis and DNA damage and by harmonizing alcohol and lipid
      metabolism.

PMID- 29048676
TI  - Decreased expression of the augmenter of liver regeneration results in growth
      inhibition and increased chemosensitivity of acute T lymphoblastic leukemia
      cells.
AB  - Augmenter of liver regeneration (ALR) plays crucial roles in cell survival and
      growth. Previous studies have demonstrated that ALR exerts a protective effect on
      toxic agent-induced cell death in acute T lymphoblastic leukemia cells and ALR
      knockdown can sensitize cancer cells to radiation. However, the biological
      functions of ALR against drug resistance in T-cell acute lymphoblastic leukemia
      are mostly unknown. In the present study, we investigated the effect of small
      interfering RNA (siRNA)-induced ALR silencing on cell proliferation and
      sensitivity to vincristine (VCR) of Jurkat cells. We found that ALR siRNA
      effectively decreased the ALR expression, then inhibited cell growth and
      increased sensitivity to VCR in Jurkat cells. Flow cytometry assay revealed that
      the downregulation of ALR expression promoted cell apoptosis and regulated cell
      cycle distribution. Following incubation with VCR, apoptosis-related proteins,
      such as pro-PARP, pro-caspase 8, pro-caspase 3 and Bcl-2 were downregulated in
      the siRNA/ALR group. Pretreatment with siRNA/ALR in combination with VCR resulted
      in prolonged G2/M arrest, accompanied by downregulation of cdc25c and cdc2
      expression and dissociation of cyclin B1. In conclusion, the results of this
      study demonstrated that targeted inhibition of the ALR expression in Jurkat cells
      triggered cell growth inhibition and sensitized cells to VCR via promoting
      apoptosis and regulating the cell cycle.

PMID- 29048677
TI  - MicroRNA-154 as a prognostic factor in bladder cancer inhibits cellular
      malignancy by targeting RSF1 and RUNX2.
AB  - Recent studies have demonstrated that microRNA-154 (miR-154) is involved in
      tumorigenesis, progression, invasion and metastasis in several types of human
      cancer. However, whether it plays a role in bladder cancer (BC) is unclear. The
      aim of the present study was to determine miR-154 levels in human BC tissues and
      investigate the correlation between miR-154 levels and clinicopathological
      characteristics as well as patient outcome. Using RT-qPCR, we found that the
      expression levels of miR-154 were significantly lower in BC tissues compared to
      adjacent normal tissues. We also demonstrated that downregulation of miR-154 was
      associated with advanced clinicopathological features and worse prognoses for
      patients with BC. Using a variety of integrated approaches, we demonstrated that
      both runt-related transcription factor 2 (RUNX2) and remodeling and spacing
      factor 1 (RSF1) were miR-154 targets. Notably, there was an inverse correlation
      between RSF1, RUNX2 and miR-154 expression in BC tissues. The biological
      functions of miR-154 were examined in vitro using Cell Counting Kit-8 (CCK-8),
      wound healing, and Transwell assays with T24 human bladder carcinoma cells
      transfected with miR-154 mimics or negative controls. These assays demonstrated
      that miR-154 significantly suppressed proliferation, migration and invasion of
      T24 cells (P<0.05). Furthermore, overexpression of RSF1 and RUNX2 rescued miR-154
      induced inhibition of these aggressive behaviors. Our results indicated that miR
      154, and its downstream targets RSF1 and RUNX2, are promising options for future
      BC therapies.

PMID- 29048678
TI  - Suppression of STIM1 inhibits the migration and invasion of human prostate cancer
      cells and is associated with PI3K/Akt signaling inactivation.
AB  - Store-operated calcium entry (SOCE) plays an important role in the invasion and
      migration of cancer cells. Stromal-interacting molecule 1 (STIM1) is a critical
      component in the SOCE. STIM1 has been attracting more and more attention due to
      its oncogenic potential. STIM1 inhibition suppresses cell proliferation,
      migration and invasion in a variety of cancer models both in vitro and in vivo.
      However, the role of STIM1 in prostate carcinogenesis, in particular, in tumor
      migration and invasion is unclear. Herein, we downregulated STIM1 in prostate
      cancer cells by lentivirus-mediated short hairpin (shRNA), and then studied its
      impacts on cell migration and invasion. We found that migration and invasion of
      prostate cancer cells were significantly inhibited after the suppression of
      STIM1. Furthermore, we demonstrated that the PI3K/Akt signaling pathway was
      inactivated by STIM1 knockdown. The PI3K inhibitor LY294002 synergized with STIM1
      knockdown to inhibit cell motility. Our results revealed that STIM1 may act as a
      novel regulator to promote migration and invasion of prostate cancer cells and is
      associated with the activation of the PI3K/Akt signaling pathway.

PMID- 29048679
TI  - Enhanced wild-type p53 expression by small activating RNA dsP53-285 induces cell
      cycle arrest and apoptosis in pheochromocytoma cell line PC12.
AB  - Malignant pheochromocytoma (PHEO) is diagnosed only when metastasis has occurred,
      making it less likely for patients to obtain the benefits of traditional
      chemotherapy. Anti-oncogene TP53 mutation has been detected in PHEO and is
      possibly related to disease progression. However, whether the upregulation of
      wild-type TP53 has antitumoral effects on PHEO remains completely unknown. In the
      present study, we used RNA activation (RNAa) technique to upregulate the
      expression of wild-type TP53 by transfecting synthetic dsP53-285 into PHEO cell
      line PC12. We found that the upregulation of wild-type p53 blocked the transition
      of PC12 cells from the G0/G1 to the S phase, with induction of apoptosis.
      Additionally, the above-mentioned findings were attested in vivo. Most
      importantly, dsP53-285-induced antitumoral effects were reversible following co
      transfection with siRNA that targeted p53 mRNA. Collectively, our results
      revealed that the upregulation of p53 and possibly other anti-oncogenes may
      provide a potential effective therapeutic strategy for PHEO.

PMID- 29048680
TI  - miR-146b-5p suppresses glioblastoma cell resistance to temozolomide through
      targeting TRAF6.
AB  - Temozolomide (TMZ), as a kind of alkylating agent, is widely utilized for the
      treatment of glioblastoma (GBM). However, temozolomide resistance (TR) often
      develops quickly and results in tumor recurrence and poor outcome. Recent
      advances have demonstrated that miRNAs exert critical roles in chemoresistance.
      Downregulation of miR-146b-5p promotes glioma cell proliferation, reduces
      apoptosis, and correlates with poor survival of patients. Nonetheless, the
      function of miR-146b-5p in temozolomide resistance remains unclear. In the
      present study, we successfully generated U87 and U251-TR cells, and found that
      miR-146b-5p was downregulated in TR cells. Overexpression of miR-146b-5p restored
      sensitivity of U87/U251-TR cells to TMZ by targeting tumor necrosis factor
      receptor-associated factor 6 (TRAF6). The levels of TRAF6 were inversely related
      to miR-146b-5p levels, and overexpression of TRAF6 in miR-146b-5p-OE cells
      enhanced the resistance against TMZ. Moreover, temozolomide-resistant GBM cells
      had a higher level of phosphorylated protein kinase B (AKT) and P65.
      Overexpression of miR-146b-5p or TRAF6 knockdown significantly decreased the
      level of p-AKT and p-p65. Collectively, our data demonstrated that miR-146b-5p,
      as a tumor suppressor, mediated temozolomide resistance in GBM cells through
      negatively regulating TRAF6 expression, indicating that miR-146b-5p and its
      targeted genes would be potential therapeutic targets for glioma therapy.

PMID- 29048682
TI  - SNHG15 affects the growth of glioma microvascular endothelial cells by negatively
      regulating miR-153.
AB  - Malignant glioma, the most common intracranial primary tumor, is characterized by
      increased angiogenesis. Accumulating evidence has shown that long non-coding RNAs
      (lncRNAs) play an important role in a variety of biological behaviors of tumors.
      However, the role of lncRNAs in the regulation of glioma vascular endothelial
      cell function remains to be investigated. To simulate the glioma
      microenvironment, we applied glioma conditioned medium (GCM) to human cerebral
      microvascular endothelial cells (hCMECs). In the present study, the lncRNA SNHG15
      was found to be highly expressed in glioma vascular endothelial cells. Cell
      Counting Kit-8 (CCK-8), migration and tube formation assays demonstrated that
      knockdown of SNHG15 inhibited glioma vascular endothelial cell proliferation,
      migration and tube formation in vitro. Furthermore, knockdown of SNHG15
      downregulated the expression of VEGFA and Cdc42, which are known to promote
      angiogenesis. Bioinformatics software and dual-luciferase system analysis
      confirmed that SNHG15 affected endothelial cell function by targeting miR-153.
      Additionally, the present study showed that miR-153 targeted the 3'-untranslated
      region of VEGFA and Cdc42 and downregulated their expression. In conclusion,
      knockdown of SNHG15 downregulated the expression of VEGFA and Cdc42 by targeting
      miR-153, consequently suppressing glioma vascular endothelial cell proliferation,
      migration and tube formation. Therefore, SNHG15 and miR-153 are new potential
      therapeutic targets for anti-angiogenesis treatment of glioma.

PMID- 29048681
TI  - Effects of FSTL1 on cell proliferation in breast cancer cell line MDA-MB-231 and
      its brain metastatic variant MDA-MB-231-BR.
AB  - In the past decades, altered Follistatin-like 1 (FSTL1) expression has been
      documented in a variety of cancers, while its functional roles are poorly
      understood. Particularly in breast cancer, the expression of FSTL1 and its
      signaling pathway remain to be determined. In the present study, an elevated
      FSTL1 expression and a supressed cell proliferation were detected in a specific
      brain metastatic cell line MDA-MB-231-BR (231-BR), compared with its parental
      cell line MDA-MB-231. However, this protein was hardly detected in the other
      three breast cancer cell lines. Next, lentiviral vectors encoding FSTL1 or FSTL1
      specific shRNAs were used to overexpress or knock down FSTL1 in MDA-MB-231 or 231
      BR, respectively (MDA-MB-231FSTL1 or 231-BRsh FSTL1). Results showed that
      overexpression of FSTL1 inhibited MDA-MB-231 cell proliferation, while knockdown
      of FSTL1 in 231-BR cells promotes cell proliferation, compared with their
      corresponding control groups. These results were further confirmed in nude mouse
      xenografts. The tumor volume in 231-BR cell-bearing mice was significantly
      smaller than that of MDA-MB-231 group, and reduction of tumor volume was detected
      in MDA-MB-231FSTL1 cell-bearing mice compared with the control group. Previous
      studies revealed that TGF-beta-Smad2/3 signaling pathway was activated in 231-BR
      and MDA-MB-231FSTL1 cells, which may contribute to the inhibited cell
      proliferation. In addition, Smad3 knockdown could restore the inhibition of cell
      proliferation induced by FSTL1 overexpression in MDA-MB-231FSTL1 cells,
      indicating that the anti-proliferative effect of FSTL1 overexpression may be
      associated with Smad3 involved TGF-beta signaling pathway regulation. This study
      identified FSTL1 as an inhibitor of cell proliferation in MDA-MB-231 and 231-BR
      cell lines, which may provide new insights into the development and management of
      breast cancer.

PMID- 29048683
TI  - Long non-coding RNA PAR5 inhibits the proliferation and progression of glioma
      through interaction with EZH2.
AB  - Emerging evidence suggests that long non-coding RNAs (lncRNAs) may be involved in
      modulating various aspects of tumor biology and serve as potential therapeutic
      targets as well as novel biomarkers in the treatment of glioma. The present study
      investigated the role of lncRNA, Prader Willi/Angelman region RNA 5 (PAR5; also
      known as PWAR5), in glioma and its clinical significance in glioma cases. The
      expression levels of PAR5 were determined in clinical samples and U87, U251 cells
      using real-time reverse transcription quantitative polymerase chain reaction (qRT
      PCR) analysis. The effects of PAR5 on cell proliferation, migration and invasion
      were determined using in vitro assays. RNA immunoprecipitation (RIP) and RNA pull
      down assays, as well as the evauation of the expression of various oncogenes were
      carried out to reveal the underlying mechanisms. We found that PAR5 was
      significantly downregulated in glioma tissues and cell lines. Furthermore, PAR5
      expression was negatively correlated with tumor size, World Health Organization
      (WHO) grade and Karnofsky performance score (KPS). Patients with low PAR5
      expression in tumors had a worse overall survival compared to those with higher
      expression. Finally, in vitro restoration of PAR5 expression inhibited human
      glioma cell proliferation, invasion and migration by binding to EZH2 and
      regulating oncogene expression. This finding may provide a therapeutic approach
      for the future treatment of glioma.

PMID- 29048684
TI  - miR-146a and miR-146b in the diagnosis and prognosis of papillary thyroid
      carcinoma.
AB  - The present study investigated the relationship between the expression of miR
      146a and miR-146b with the occurrence and prognosis of papillary thyroid
      carcinoma. Experiments in vitro were also used to explore the effect of the
      knocked down expression of the miRNAs on growth and migration of papillary
      thyroid carcinoma cells. A total of 73 patients with papillary thyroid carcinoma
      admitted to Yidu Central Hospital of Weifang from September 2013 to September
      2015 were enrolled in the study. Carcinoma samples were obtained from each
      patient, and adjacent tissues were used as control samples to determine
      expression levels of miR-146a and miR146b by semi-quantitative RT-PCR. An
      analysis was conducted to find possible correlations between the miRNAs
      expression levels and clinicopathological features in the patients followed up
      for one year after diagnosis. Additionally, to examine the function of miR-146a
      and miR-146b on TPC-1 cells, the expression of miRNAs was knocked down using
      specific siRNAs. MTT and Transwell assays were used to evaluate cell
      proliferation and migration, respectively, in the miRNA cell lines. Finally,
      western blot analysis was used to analyze the expression of IRAK1 in PTC cancer
      cells. Our results showed that the expression levels of miR-146a and miR-146b in
      carcinoma tissues were significantly higher than the levels in cancer-free
      tissues (p<0.01). The relative expression levels of miR-146a and miR-146b in
      cancerous tissues could be associated with the pathological type and presence or
      absence of lymph node metastasis (p<0.05). Compared with the siRNA-control cell,
      MTT and Transwell assays showed that the cell growth and migration of TPC-1 cells
      were decreased in miR-146a and miR-146b low expression cells (p<0.01). Western
      blot analysis showed that the expression of IRAK1 in papillary thyroid carcinoma
      was higher than in adjacent tissue (p<0.01). Based on our findings, the
      expression of miR-146a and miR-146b correlates with the occurrence and prognosis
      of papillary thyroid carcinoma, and the expression levels of miR-146a and miR
      146b seem to affect the cell proliferation and migration and regulate the
      expression of IRAK1 protein in cancer cells. Further studies are needed to
      validate our results to provide new targets for prevention and treatment of
      papillary thyroid carcinoma.

PMID- 29048685
TI  - miR-504 promotes tumour growth and metastasis in human osteosarcoma by targeting
      TP53INP1.
AB  - An increasing number of studies have demonstrated that microRNAs participate in
      the development of osteosarcoma by acting as tumour suppressor or tumour
      promoting genes. We investigated the role of miR-504 in the growth and metastasis
      of osteosarcoma. The expression of miR-504 in clinical osteosarcoma samples was
      higher than that in the adjacent normal tissue and correlated with tumour size
      and clinical stage. Tumour protein p53-inducible nuclear protein 1 (TP53INP1) was
      downregulated in the clinical osteosarcoma samples compared with the adjacent
      normal tissues and was consistently correlated with the clinical stage. The
      results of dual-luciferase reporter assay and western blot analysis demonstrated
      that the TP53INP1 gene is a direct target of miR-504. Altogether, the Cell
      Counting Kit-8 (CCK-8), the colony formation, the flow cytometry and the
      Transwell assay results demonstrated that miR-504 promoted osteosarcoma cell
      growth and metastasis in vitro. P73, P21, Bax, cleaved-caspase-3 and secreted
      protein acidic and rich in cysteine (SPARC) were associated with the suppressive
      role of miR-504/TP53INP1. The overexpression of miR-504 in osteosarcoma
      xenografts enhanced the tumour growth and increased the metastatic burden.
      Collectively, these results revealed that TP53INP1 is a target gene of miR-504
      and that miR-504 enhances osteosarcoma growth and promotes distant metastases by
      targeting TP53INP1. Thus, miR-504/TP53INP1 may be associated with osteosarcoma
      size and clinical stage.

PMID- 29048686
TI  - miR-1908 as a novel prognosis marker of glioma via promoting malignant phenotype
      and modulating SPRY4/RAF1 axis.
AB  - MicroRNAs (miRNAs) are reported to be involved in the development of glioma.
      However, study on miRNAs in glioma is limited. The present study aimed to
      identify miRNAs which can act as potential novel prognostic markers for glioma
      and analyze its possible mechanism. We show that miR-1908 correlates with shorter
      survival time of glioma patients via promoting cell proliferation, invasion, anti
      apoptosis and regulating SPRY4/RAF1 axis. Analysis of GEO and TCGA database found
      that miR-1908 was significantly upregulated in glioma tissues, and strongly
      associated with shorter survival time of glioma patients. Further Gene Ontology
      (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that
      miR-1908 is mainly involved in regulating cell proliferation, invasion and
      apoptosis. To further confirm the above results, in vitro, glioma U251 cells were
      transfected with miR-1908 mimics or inhibitor, and upregulated miR-1908 promoted
      U251 cell proliferation, and enhanced the ability of invasion by transwell assay.
      In addition, upregulated miR-1908 also enhanced anti-apoptosis ability of U251
      cells through decreasing pro-apoptosis protein Bax expression. Since miRNAs
      regulate numerous biological processes by targeting broad set of messenger RNAs,
      validated target genes of miR-1908 in glioma were analyzed by Targetscan and
      miRTarBase databases. Among them SPRY4 was significantly decreased in glioma
      tissues and associated with short survival time, which was selected as the key
      target gene of miR-1908. Moreover, protein-protein interaction (PPI) showed that
      SPRY4 could interacted with pro-oncogene RAF1 and negatively correlated with RAF1
      expression. Consistent with above analysis, in vitro, western blot analysis
      identified that miR-1908 upregulated significantly decreased SPRY4 expression and
      increased RAF1 expression. Hence, miR-1908 was correlated with poor prognosis of
      glioma via promoting cell proliferation, invasion, anti-apoptosis and regulating
      SPRF4/RAF1 axis. Our results elucidated the tumor promoting role of miR-1908 and
      established miR-1908 as a potential novel prognostic marker for glioma.

PMID- 29048688
TI  - Is endoprosthetic replacement of the proximal femur appropriate in the comorbid
      patient?
AB  - INTRODUCTION: Patients with failed hip arthroplasty requiring extensive femoral
      reconstruction often present with a multitude of comorbidities. Many treatment
      options limit initial mobilisation relying on bone graft incorporation. The use
      of endoprosthetic replacement (EPR), despite often being a "last resort", offers
      an expeditious solution with early mobilisation that is crucial in the comorbid
      individual. Many perceive that the surgical insult of EPR is associated with an
      increased mortality. The aim of this study was to report our experience of
      proximal femoral EPR as the treatment for failed arthroplasty or fracture
      fixation. Primary outcomes included mortality, complications, revision and
      function. METHODS: Retrospective review of proximal femoral EPR undertaken at our
      institution for non-oncological indications between 2007 and 2015 identified 37
      patients with a mean follow-up of 33 months. Patient case notes, demographics and
      radiographs were studied. RESULTS: The 90-day mortality following proximal
      femoral EPR was 2.7%. 9 patients had died at the time of final follow-up (mean
      time to death was 33 months). The mean preoperative and postoperative Oxford Hip
      Score improved from 8 to 31 respectively (p<0.05). When considering revision for
      any cause, 5-year survival was 94.6%. 2 patients suffered periprosthetic joint
      infection and 1 patient required revision for prosthesis dislocation.
      CONCLUSIONS: We report a relatively low incidence of perioperative complications,
      with a mortality rate similar to other revision options in this high-risk cohort.
      Whilst further revision may not always be possible, this "last resort" technique
      is safe in the comorbid population presenting with significant proximal femoral
      bone deficiency.

PMID- 29048687
TI  - SP1 promotes tumor angiogenesis and invasion by activating VEGF expression in an
      acquired trastuzumab-resistant ovarian cancer model.
AB  - Ovarian cancer is one of the most common gynecologic cancers and the leading
      cause of mortality in women worldwide. HER2/neu is overexpressed in various types
      of cancers and is most commonly associated with decreased survival. Trastuzumab
      is a humanized anti-HER2 monoclonal antibody for the treatment of HER2-positive
      breast cancers. However, primary and/or acquired resistance occurs in up to 62%
      patients during the first year of treatment. Vascular endothelial growth factor
      (VEGF) is a well-known angiogenesis factor involved in many physiological and
      pathological processes. Its significance has been implicated in promoting tumor
      growth and metastasis via angiogenesis. In the present study, we demonstrated
      that the upregulation of SP1 enhanced expression of VEGF promoting the
      angiogenesis and migration of trastuzumab-resistant ovarian cancer cell line
      SKOV3-T. Our in vitro and in vivo results both gave evidence that the SP1-VEGF
      axis was responsible for the enhanced malignancy, angiogenesis and migration in
      the acquired trastuzumab-resistant ovarian cancer cell model.

PMID- 29048689
TI  - Long-term clinical results of the Metasul metal-on-metal total hip arthroplasty:
      12.6 years follow-up of 128 primary total hip replacements.
AB  - INTRODUCTION: The purpose of the present study is to report the long-term
      clinical results of an uncemented total hip arthroplasty (THA) using a Metasul
      metal-on-metal (MoM) 28-mm bearing and to evaluate the long-term serum cobalt
      levels. METHODS: At an average of 12.6 years following primary THA, we
      retrospectively reviewed the clinical results of the first 116 consecutive
      patients (128 THAs) in our institution who underwent 28-mm Metasul MoM THA. Of
      the 78 patients who were able to visit our outpatient clinic, serum cobalt levels
      were evaluated. RESULTS: The overall survival rate of the cohort was 96.1% (95%
      confidence interval [CI], 93.2-99.6), 12.6 years (95% CI, 12.3-12.7 years)
      following surgery. 3 patients had undergone revision due to aseptic loosening of
      the stem and 2 patients sustained a periprosthetic fracture. The average modified
      Harris Hip Score was 90 (72-97) and the average Oxford Hip Score was 56 (48-60),
      representing both excellent outcome scores. The average serum cobalt of the
      entire cohort was 20.1 nmol/L (range 8.5-227.7 nmol/L). Serum cobalt levels of
      patients with a bilateral MoM THA were significantly higher (35.0 nmol/l,
      p<0.01). No relation between serum cobalt levels, subjective outcome, radiolucent
      lines on radiographs and survivorship of the implant was noted. CONCLUSIONS: Long
      term results of the metasul MoM bearing articulation in THA seem to be excellent,
      although cobalt serum levels should be monitored closely.

PMID- 29048690
TI  - Large fresh osteochondral allografts for the hip: growing the evidence.
AB  - INTRODUCTION: Articular cartilage lesions of the hip are difficult to effectively
      treat. Osteochondral allograft (OCA) transplantation in the knee has been
      associated with long-term success, but OCA for the hip has not been extensively
      studied. Here, we present the clinical and radiological outcomes from a cohort of
      10 patients treated with fresh OCA transplants for large osteochondral defects of
      the femoral head and/or acetabulum. METHODS: 10 patients who had undergone
      osteochondral allograft transplantation of the femoral head and/or acetabulum at
      our institution between 2013 and 2016 were identified from our Institutional
      Review Board-approved registry. Hip disability and Osteoarthritis Outcome Score
      (HOOS) was used to track patient progress. RESULTS: 10 patients with an average
      clinical follow-up of 1.4 years were included in this study. 4 patients were
      treated solely with OCA plugs for femoral head defects, while the remaining 6
      received femoral OCA plugs and at least 1 concomitant procedure for additional
      intraarticular pathology. 7 patients (70%) had successful functional outcomes,
      while 3 (30%) had unsuccessful outcomes and were subsequently converted to total
      hip arthroplasty (THA) 5 to 29 months after OCA. CONCLUSIONS: OCA transplantation
      can be an effective treatment strategy for young, healthy individuals with
      articular cartilage lesions of the hip. Smoking, avascular necrosis aetiology,
      acetabular involvement and concomitant procedures may be risk factors for
      unsuccessful outcomes necessitating salvage with THA. Long-term clinical studies
      to refine indications and determine functional outcomes and survival rates are
      warranted.

PMID- 29048691
TI  - Is a short stem suitable for patients with hip dysplasia? A report on technical
      problems encountered during femoral reconstruction.
AB  - INTRODUCTION: A wide variety of stems have been used for the treatment of
      osteoarthritis secondary to advanced hip dysplasia. Since evidence for using
      short stems in dysplastic hips is limited, we planned to analyse the technical
      problems encountered when reconstructing the proximal femur of patients with
      osteoarthritis secondary to congenital dysplasia of the hip treated with total
      hip arthroplasty (THA) using a type 2B short stem. METHODS: We prospectively
      analysed 17 patients (22 hips) treated with primary THA performed with a single
      branded short uncemented stem with metaphyseal fixation (MiniHipTM; Corin). We
      excluded cases in which other type of stems were used, or in which retrospective
      data was only available. Mean follow-up was 41.22 months (minimum 24). We
      analysed clinical outcome using the modified Harris Hip Score (mHHS) and pain
      using the visual analogue scale (VAS). Radiographs were examined in order to
      determine causes of complications and revision surgery. RESULTS: All patients
      showed statistically significant improvement when preoperative and postoperative
      values for mHHS (54.19 vs. 94.57; p = 0.0001) and for pain VAS (8.71 vs. 0.71; p
      = 0.0003) were compared. No cases of thigh pain, instability or infection were
      found. 1 case of acetabular cup loosening and 1 case of periprosthetic fracture
      were diagnosed at 8 months and 45 days, respectively. Overall survival was 84.7%
      at 5 years (CI 95%, 64.4-105.3) with revision for any reason as an end point.
      When stem performance was separately evaluated, it showed a survival rate of 100%
      at 5 years with revision for aseptic loosening as an end point. CONCLUSIONS: THA
      with a type 2B short stem for the treatment of dysplastic osteoarthritis showed
      very few technical intraoperative problems, being a useful alternative for
      femoral reconstruction.

PMID- 29048692
TI  - Effects of electrical stimulation in the treatment of osteonecrosis of the
      femoral head.
AB  - INTRODUCTION: The aim of this study was to examine whether the use of an internal
      electrostimulator could improve the results obtained with core decompression
      alone in the treatment of osteonecrosis of the femoral head. METHODS: We
      performed a retrospective study of 41 patients (55 hips) treated for
      osteonecrosis of the femoral head between 2005 and 2014. Mean follow-up time was
      56 (12-108) months. We recorded 3 parameters: time to recurrence of pain, time to
      conversion to arthroplasty and time to radiographic failure. Survival was
      estimated using the Kaplan-Meier method. The equality of the survival
      distributions was determined by the Log rank test. RESULTS: Implanted
      electrostimulator was a factor that increased the survival of hips in a pre-op
      Steinberg stage of II or below, while it remained unchanged if the stage was III
      or higher. CONCLUSIONS: The addition of an internal electrostimulator provides
      increased survival compared to core decompression alone at stages below III.

PMID- 29048693
TI  - Risk factors for conversion surgery to total hip arthroplasty of a
      hemiarthroplasty performed for a femoral neck fracture.
AB  - INTRODUCTION: The purpose of this study was to determine risk factors for
      conversion to total hip arthroplasty (THA) in patients originally treated with
      hemiarthroplasty (HA) for displaced femoral neck fractures. METHODS: In this case
      controlled study, we identified 54 patients who were treated with HA for femoral
      neck fracture (FNF) who subsequently underwent conversion to THA at our
      institution between 2003 and 2013. We randomly selected 142 control patients who
      underwent HA for a displaced FNF without conversion surgery during the same time
      period. We compared demographic data, implant parameters, and radiographic data
      between the groups to identify risk factors for conversion surgery. RESULTS: In
      the univariate analysis, younger age at index surgery (mean 75 vs. 80 years, p =
      0.006), higher body mass index (26.1 vs. 23.7, p = 0.031), bipolar prosthesis
      (20% vs. 36%, p = 0.024), absence of dementia (6% vs. 23%, p = 0.01), increased
      leg length compared to contralateral limb (6.5 mm vs. 0.2 mm, p<0.001), and
      increased HA femoral head size compared to the contralateral femoral head (2.7 mm
      vs. 1.5 mm, p = 0.02) were associated with a significantly increased risk of
      conversion surgery. In the multivariate logistic regression, decreased age at
      index surgery, no dementia, use of a bipolar head, and increased leg length
      discrepancy (LLD) were associated with risk of conversion. CONCLUSIONS: Patient
      characteristics, including younger age, increased BMI, and absence of dementia
      can lead to increased risk for conversion of HA to THA. Intraoperative
      considerations of head size and increase in ipsilateral LLD may increase the risk
      of conversion surgery. These factors should be considered by surgeons who employ
      HA for displaced FNFs.

PMID- 29048694
TI  - Effect of sleeved ceramic femoral heads on titanium ion release.
AB  - INTRODUCTION: Metal ion release from wear and corrosion at the femoral head-stem
      taper junction can evoke local adverse reactions to metal debris (ARMD). In a
      specific large-diameter head (LDH) total hip arthroplasty (THA) system, ceramic
      femoral heads of 44 to 48 mm are available with a titanium (Ti) adaptor sleeve,
      while heads of 36- to 40-mm come without sleeves. The hypothesis of this study is
      that the Ti adaptor sleeve with LDH ceramic-on-ceramic (CoC) bearings will not
      cause wear or corrosion at the taper junction and, thus, will not generate high
      whole blood Ti ion levels. METHODS: We compared whole blood Ti levels at minimum
      1-year follow-up in 27 patients with unilateral primary LDH CoC THA with head
      sizes ranging from 36 to 48 mm using a Ti stem and acetabular component. RESULTS:
      Although Ti ion levels in patients with 36- to 40-mm head diameters without Ti
      sleeve were found to be statistically significantly higher (2.3 MUg/l: 1.6-3.1,
      SD 0.44) compared to those with a Ti sleeve (1.9 MUg/l: 1.6-2.2, SD 0.19) (p =
      0.020), the found difference has no clinical importance. No patients presented
      clinical signs of ARMD, and the clinical results in both groups were similar.
      CONCLUSIONS: LDH CoC THA Ti levels were low and probably related to unavoidable
      passive corrosion of implant surfaces. Measurement of Ti in subjects with ceramic
      LDH, with or without Ti adaptor sleeve, did not disclose undirected signs of
      trunnionosis.

PMID- 29048696
TI  - The direct anterior minimal invasive approach in total hip replacement: a
      prospective departmental study on the learning curve.
AB  - INTRODUCTION: Introduction of new surgical techniques is normal, but seldom
      monitored in real time. The purpose of this study was to monitor the learning
      curve when introducing a new surgical technique to a department. We did a
      prospective evaluation of the learning curve when introducing the minimally
      invasive direct anterior approach in total hip arthroplasty. We wish to
      investigate whether there is a learning curve for the direct anterior minimal
      invasive approach in total hip replacement and what are the early complications
      to this approach. METHODS: The department changed from the direct lateral
      approach to the minimally invasive direct anterior approach. We monitored the
      first 522 patients operated using this approach with regards to patient outcome
      scores and complications 6 months postoperatively. RESULTS: The last 250 patients
      operated all had significantly better results with regard to patient outcome
      scores and cup placement. We investigated 100 patients at a time and compared
      them with the rest of the patient and found the same pattern. This pattern ends
      when we reach patients somewhere between 200-300. DISCUSSIONS: We established the
      learning curve on a departmental level with regards to introduction of the
      minimal invasive direct anterior approach. We see a steady improvement in scores
      with regards to patient outcome scores and cup positioning until we reach a
      steady-state. The learning curve here flattens out. Departments must understand
      that one should expect early complications and somewhat less than optimal results
      at first when introducing this new surgical technique.

PMID- 29048695
TI  - Evaluation of late redislocation in patients who underwent open reduction and
      pelvic osteotomy as treament for developmental dysplasia of the hip.
AB  - INTRODUCTION: The goal in the treatment of developmental dysplasia of the hip
      (DDH) is to achieve a stable and concentric reduction and to create a congruent
      relationship between the femoral head and the acetabulum. This study discusses
      the causes of loss of reduction in DDH patients who had a concentrically reduced
      hip at the time of removal of the hip spica cast and cessation of brace use and
      who later appeared with hip redislocation after mobilisation and ambulation. In
      addition, the possible interventions in such cases are also discussed. MATERIAL
      AND METHOD: A retrospective evaluation was made of 13 patients diagnosed with DDH
      who developed redislocation following primary surgery. 6 of them had undergone
      the 1st surgery in our department between 2008 and 2016 and 7 had udergone
      surgery in another centre. For comparison reasons a 2nd group was formed of 13
      demographically and clinically matched patients who had no loss of reduction. The
      groups were compared in terms of acetabular index, pelvic length, pelvic width,
      abduction degree of plaster, ossifying nucleus diameter, acetabular depth, and
      acetabular volume parameters. RESULTS: The average age of the patients was 23
      months at initial surgery and 29 months at the time of revision surgery. No
      significant difference was found between the groups in terms of acetabular
      inclination angle, ossifying nucleus diameter, pelvic size, pelvic width, centre
      edge angle, acetabular volume, and depth. Contracted inferomedial capsule was
      found in 1 patient who underwent revision surgery and intact transverse
      acetabular ligament was seen in 1 patient. The loss of reduction in the remaining
      11 patients was associated with high total anteversion of the femoral head and
      acetabulum. CONCLUSIONS: Correction of increased combined anteversion by femoral
      osteotomy can create a safe zone in terms of redislocation and can significantly
      contribute to the stability provided by capsulorrhaphy and pelvic osteotomy.

PMID- 29048697
TI  - Comparison of arthroscopic versus open surgery on external snapping hip caused by
      gluteal muscle contracture.
AB  - PURPOSE: To compare the outcomes of contracture release by arthroscopic versus
      open surgical approach in patients with external snapping hip (ESH) caused by
      gluteal muscle contracture (GMC). METHODS: Medical records of patients with ESH
      due to GMC who underwent open surgery (n = 44) or arthroscopic surgery (n = 48)
      between October 2008 and October 2014 were reviewed. Patients were followed up at
      1, 3, 12, and 24 months postoperatively. Operation time, incision length,
      postoperative pain, postoperative complication rate, and recurrence rate were
      compared between the 2 groups. Hip adduction, and Harris Hip Scores (HHS) at 1
      and 2 years postoperatively were compared between the groups and with
      preoperative data. RESULTS: Mean operation time did not differ between the 2
      groups (p>0.05). The arthroscopic surgery group had smaller incisions (p<0.05),
      less postoperative pain (p<0.05), lower complication rates (p<0.05) than did the
      open surgery group. The recurrence rates were similar for the 2 groups (p>0.05).
      Hip adduction, and HHS 1 year and 2 years postoperatively were significantly
      better postoperatively than they had been preoperatively for both groups (all
      p<0.01), and were similar for the 2 groups (all p>0.05). CONCLUSIONS:
      Arthroscopic release of contracture tissue is a safe and effective approach for
      the treatment of ESH caused by GMC, with the advantages of small scars, less
      postoperative pain, fewer complications compared with open surgery.

PMID- 29048698
TI  - Soft tissue reinforcement with a Leeds-Keio artificial ligament in revision
      surgery for dislocated total hip arthroplasty.
AB  - INTRODUCTION: Since dislocation after total hip arthroplasty (THA) greatly
      diminishes patient's quality of life, the THA frequently needs revision. However,
      it is common for the dislocation not to heal even after reconstruction, but
      rather to become intractable. METHODS: The 17 patients with dislocated THA, mean
      age of 71 years (range 51-87 years), who underwent a revision THA together with
      soft tissue reinforcement with a Leeds-Keio (LK) ligament were enrolled. The
      purposes of reinforcement with LK ligament were to restrict the internal rotation
      of the hip joint, and to encourage the formation of fibrous tissue in the
      posterior acetabular wall to stabilise the femoral head. We determined the
      success rate of surgical treatment for dislocation, the Harris Hip Score (HHS), a
      factor of recurrent dislocation. RESULTS: There was no recurrent dislocation in
      82% of the cases (14 joints) during the mean postoperative follow-up period of
      63.5 months (15-96 months). The HHS was 82 +/- 18 points preoperatively and 82 +/
      14 points postoperatively. Recurrent dislocation after this surgical procedure
      occurred in 2 hips with breakage of the LK ligaments, and intracapsular
      dislocation in 1 hip with loosening of the LK ligament. CONCLUSIONS: Although the
      risk of recurrent dislocation still exists with this procedure, when performed to
      provide reinforcement with an LK ligament for dislocated THA it may be useful in
      intractable cases with soft tissue defects around the hip joint.

PMID- 29048699
TI  - Arthroscopic treatment of psoas abscess concurrent with septic arthritis of the
      hip joint.
AB  - PURPOSE: To describe the outcomes of 7 cases of psoas abscess concurrent with
      septic arthritis of the hip treated by hip arthroscopy alone. METHODS: We
      retrospectively collected the data of patients who underwent arthroscopic
      drainage of psoas abscess concurrent with septic arthritis of the hip.
      Arthroscopic debridement was performed in both the central and peripheral hip
      joint compartments. In all cases, the iliopsoas compartment was accessed from the
      peripheral compartment through an anterior capsulotomy without limb traction.
      After debridement and drainage of the iliopsoas compartment, a suction drain tube
      was placed in the iliopsoas compartment through an enlarged anterior capsulotomy
      and another tube in the peripheral compartment. Postoperative intravenous
      antibiotics were administered on the basis of culture results; in cases with no
      positive culture, empirical antibiotics were administered for 4 to 6 weeks after
      surgery. RESULTS: 7 patients underwent arthroscopic debridement and drainage for
      a psoas abscess concurrent with hip joint septic arthritis. Laboratory tests were
      normalized within 4 weeks after hip arthroscopy in all patients. At a median
      follow-up of 16 months (range, 13-30 months) after surgery, infection recurrence
      was absent in all patients. CONCLUSIONS: Arthroscopic debridement alone could be
      an effective treatment alternative to open surgery for psoas abscess concurrent
      with hip joint septic arthritis.

PMID- 29048700
TI  - Erratum to: Circulating tumor markers: a guide to their appropriate clinical use
      | Comparative summary of recommendations from clinical practice guidelines (PART
      1), (PART 2), (PART 3).
AB  - Erratum To: Circulating tumor markers: a guide to their appropriate clinical use
      | Comparative summary of recommendations from clinical practice guidelines (PART
      1) Gion M, Trevisiol C, Rutjes AW, Rainato G, Fabricio AS. Int J Biol Markers.
      2016 Dec 23;31(4):e332-e367. doi: 10.5301/jbm.5000251. Circulating tumor markers:
      a guide to their appropriate clinical use | Comparative summary of
      recommendations from clinical practice guidelines (PART 2).Gion M, Trevisiol C,
      Rutjes AWS, Rainato G, Fabricio ASC. Int J Biol Markers. 2017 Mar 2;32(1):e1-e52.
      doi: 10.5301/ijbm.5000259. Circulating tumor markers: a guide to their
      appropriate clinical use | Comparative summary of recommendations from clinical
      practice guidelines (PART 3).Gion M, Trevisiol C, Rutjes AWS, Rainato G, Fabricio
      ASC. Int J Biol Markers. 2017 May 4;32(2):e147-e181. doi: 10.5301/ijbm.5000272.
      We report an amendment in the Detailed summary tables pages of the three parts of
      the guidelines above. The correct definition of detailed summary tables is
      reported below. Definition and target audience Detailed summary tables are tables
      prepared for every tumor type which report recommendations and supplementary
      information from different guidance documents with enough details to be useful
      for health care providers, policy makers (for potential adaptation to specific
      settings) and staff developing educational material informed by available
      evidence.

PMID- 29048701
TI  - Medical Devices; Clinical Chemistry and Clinical Toxicology Devices;
      Classification of the Organophosphate Test System. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the organophosphate
      test system into class II (special controls). The special controls that apply to
      the device type are identified in this order and will be part of the codified
      language for the organophosphate test system's classification. We are taking this
      action because we have determined that classifying the device into class II
      (special controls) will provide a reasonable assurance of safety and
      effectiveness of the device. We believe this action will also enhance patients'
      access to beneficial innovative devices, in part by reducing regulatory burdens.

PMID- 29048702
TI  - Time-kill assays of amphotericin B plus anidulafungin against Candida tropicalis
      biofilms formed on two different biomaterials.
AB  - PURPOSE: To determine the fungicidal activity by time-killing assays of
      amphotericin B (AMB) combined with anidulafungin (ANF) against biofilms of 2
      clinical isolates of Candida tropicalis and the reference strain ATCC(r) 750,
      developed on polytetrafluoroethylene (PTFE) and titanium, using the CDC Biofilm
      Reactor (CBR) as an in vitro model. METHODS: Biofilms were developed for 24 hours
      on the disk surfaces and then exposed to AMB (40 mg/L), ANF (8 mg/L), alone and
      combined. At predetermined time points after drug exposure, biofilms were removed
      from the disk surface by vortexing-sonication to quantify viable biofilm cells.
      RESULTS: Drug activity was dependent on strain and time. After exposure to AMB,
      the mean decrease in viable cells attached to PTFE was 2.23 +/- 0.89 Log10
      cfu/cm2 (range 0.6-3.56 Log10), and on titanium 2.91 +/- 1.04 (range 1.49-4.51
      Log10). The reduction with ANF was 0.78 +/- 0.5 (0.03-1.58 Log10) on PTFE and 0.8
      +/- 2.26 (0.42-1.16 Log10) on titanium. The reduction obtained with the
      combination of AMB + ANF was 1.8 +/- 1.07 (0.22-3.54 Log10) on PTFE and 1.97 +/-
      0.49 (1.36-2.84 Log10) on titanium. The interaction was classified as indifferent
      with a tendency to antagonism. CONCLUSIONS: The activity of antifungal agents
      depends on the biomaterial surfaces the biofilm forming capacity of the isolate.
      AMB + ANF is less effective than AMB alone on both surfaces. Thus, the
      combination of these antifungals does not seem to add additional benefits to the
      treatment of C. tropicalis biofilm-related infections.

PMID- 29048703
TI  - A pilot study on the efficacy and safety of a minimally invasive surgical and
      anesthetic approach for ventricular assist device implantation.
AB  - BACKGROUND: The aim of our study was to compare 2 surgical and anesthetic
      approaches during ventricular assist device implantation. METHODS: 68 patients
      (50.4 +/- 17.1 years old) were supported with the HeartWare(r) HVAD (32 patients)
      and the Jarvik 2000 VAD (36 patients) between January 2010 and August 2016. Two
      surgical techniques were applied: a minimally invasive approach with the aid of
      paravertebral-block (mini-invasive group, 41 patients) and a standard-surgical
      approach with the aid of general anesthesia (27 patients). RESULTS: The minimally
      invasive approach allowed faster postoperative recovery by significantly reducing
      the duration of surgery (p<0.05), anesthesia (p<0.05), mechanical ventilation
      (p<0.05), inotropic support (p<0.05), ICU and in-hospital stay (p<0.05), and time
      to first mobilization (p<0.05). No case of epidural hematoma was observed. Eleven
      patients died (16%) at 30 days, 3 in the mini-invasive group (7.3%) and 8 in the
      invasive group (29.6%). CONCLUSIONS: Minimally invasive approaches play a
      substantial role in VAD surgery by facilitating faster recovery, which is
      important for patients at very high risk.

PMID- 29048704
TI  - Hydroxyapatite decreases cytotoxicity of a glass ionomer cement by calcium
      fluoride uptake in vitro.
AB  - BACKGROUND: Glass ionomer cements (GICs) are widely used in dentistry because of
      their remineralizing and cariostatic potential induced by fluoride. In vitro
      studies have reported cell toxicity triggered by GICs; however, the influence of
      hydroxyapatite (HAp) must be considered. The aim of this study was to evaluate
      the effect of HAp in decreasing the cytotoxicity of the GIC 3M Vitrebond in
      vitro. METHODS: Samples of 3M Vitrebond (powder, liquid and light-cured) were
      incubated in Dulbecco's modified Eagle's medium-Ham's F12 (DMEM-F12) for 24 hours
      at 37 degrees C. Subsequently, the light-cured medium was treated with 100 mg/mL
      of HAp overnight. Toxicity of conditioned media diluted 1:2, 1:4, 1:8 and 1:20
      was analyzed on human gingival fibroblasts (HGFs) using light microscopy and the
      fluorometric microculture cytotoxicity assay. The amounts of calcium fluoride
      (CaF2) were determined by the alizarin red S method. RESULTS: The exposure of
      HGFs to light-cured induced cell death and morphological changes such as
      chromatin condensation, pyknotic nuclei and cytoplasmic modifications. Exposure
      to light-cured treated with HAp, significantly increased cell viability leading
      to mostly spindle-shaped cells (p<0.001). The concentration of CaF2 released by
      the light-cured was 200 ppm, although, in the light-cured/HAp conditioned medium,
      this quantity decreased to 88 ppm (p<0.01). CONCLUSIONS: These data suggest that
      HAp plays a protective role, decreasing the cytotoxic effect of 3M Vitrebond
      induced by CaF2.

PMID- 29048705
TI  - Retraction: "What role do periodontal pathogens play in osteoarthritis and
      periprosthetic joint infections of the knee?"
AB  - J Appl Biomater Funct Mater. 2014; 12(1):13-20 What role do periodontal pathogens
      play in osteoarthritis and periprosthetic joint infections of the knee? Ehrlich
      GD, Hu FZ, Sotereanos N, Sewicke J, Parvizi J, Nara PL, Arciola CR PMID: 24921460
      DOI: 10.5301/jabfm.5000203 Accepted on 09/11/2013 Available online on 02/06/2014
      Published online on 12/06/2014 The above article appeared in J Appl Biomater
      Funct Mater 2014;12(1):13-20. The studies under the clinical trial set forth in
      the article were performed with a large group of co-investigators. The principal
      investigator of the clinical trial is not listed as a co-author of this article
      and he asserts he has not validated the accuracy of the data presented in the
      article. Further, co-investigators who are unnamed authors of this article have
      produced manuscripts with data from the clinical trial. Being the duty of authors
      to submit works which have not been published in whole or in part elsewhere, and
      upon notification of the above dispute by the lead author, the article has been
      retracted.

PMID- 29048706
TI  - Assessment of monomer release from 3 different fissure sealants.
AB  - BACKGROUND: Light-activated resin-based dental fissure sealants are the most
      widely accepted among clinicians. The objective of this study was to determine
      monomer release of 3 different light-curing fissure sealants in vitro: Control
      Seal (Voco, Germany), Fissurit FX (Voco, Germany) and R&D Series Fissured Nova
      (Imicrly, Turkey). METHODS: Each material was polymerized with a curing light:
      Valo Cordless (Ultradent) LED in standard mode for 20 seconds (n = 27) and 40
      seconds (n = 27) and in Xtra power mode (plasma arc) for 3 seconds (n = 27). High
      performance liquid chromatography (HPLC) was used to measure the amount of
      monomers released over 1, 3 and 7 days. RESULTS: Plasma arc groups showed the
      highest release of monomers at 1, 3 and 7 days in the 3 fissure sealant groups
      (p<0.001). The greatest release of bisphenol A glycidyl methacrylate (bis-GMA)
      determined for R&D Series Fissured Nova both with LED 20 seconds and LED 40
      seconds and for Control Seal was with the plasma arc. With time, release of the
      monomer was reduced for all polymerization systems. CONCLUSIONS: Efficiency of
      the polymerization system and applying the recommended curing time for light
      activated resin-based dental materials are very important to protect the patient
      from potential hazards of residual monomers.

PMID- 29048707
TI  - Cancer in adolescence - the girlfriend's story.

PMID- 29048708
TI  - Effect of the midazolam added with propofol-based sedation in
      esophagogastroduodenoscopy: A randomized trial.
AB  - BACKGROUND AND AIM: Although propofol has been widely used for sedation during
      esophagogastroduodenoscopy (EGD), adverse events including hypoxia and
      hypotension may be a concern in the propofol-based sedation. We aimed to analyze
      whether administration of midazolam would improve safety and efficacy of propofol
      based sedation in EGD. METHODS: One hundred twenty patients who were scheduled to
      undergo diagnostic EGD were randomly assigned to either midazolam plus propofol
      (MP) or propofol alone groups. In the MP group, 2 mg of midazolam and 10 mg of
      propofol were given initially. In the propofol alone group, 40-60 mg of propofol
      was given initially. In both groups, 20 mg of propofol was given repeatedly to
      maintain moderate sedation as needed. Vital signs including oxygen saturation
      were monitored every 2 min. After the patients fully recovered, satisfaction
      score was investigated from endoscopists, nurses, and patients, respectively.
      RESULTS: The baseline characteristics did not differ between the MP and propofol
      alone groups. The mean required doses of propofol was (mean +/- standard
      deviation) 0.3 +/- 0.3 and 0.8 +/- 0.2 mg/kg in the MP and propofol alone groups,
      respectively (P < 0.001). In addition, sedation-related adverse events and
      recovery time did not differ between the two groups. The proportion of
      satisfactory did not differ between the two groups (MP vs propofol alone;
      proportion; patient, 95.0% vs 93.3%, P > 0.999; endoscopist, 73.3% vs 80.0%, P =
      0.064; nurse, 73.3% vs 76.7%, P = 0.551). CONCLUSION: Adding midazolam to
      propofol did not reduced the safety and efficacy, and sedation using propofol
      alone could be suitable for sedation during diagnostic EGD.

PMID- 29048709
TI  - Comparison of Percutaneous Dilatational Tracheostomy Guided by Ultrasound and
      Bronchoscopy in Critically Ill Obese Patients.
AB  - OBJECTIVES: This study aimed to compare the efficacy and safety of percutaneous
      dilatational tracheostomy (PDT) with ultrasound (US) or bronchoscopic guidance
      for critically ill patients, notably obese patients. METHODS: This work was a
      retrospective study. The study included mechanically ventilated patients who
      underwent PDT from August 2013 to July 2015 in the Department of Critical Care
      Medicine of Zhongshan Hospital. The patients were classified according to the
      different guidance methods during tracheotomy and their body mass index in the
      following 4 groups: normal bronchoscopy group, normal US group, obese
      bronchoscopy group, and obese US group. The parameters, including operation time,
      number of punctures, intraoperative and postoperative complications, duration of
      the intensive care unit stay, hospitalization time, and mortality, were recorded
      and compared between groups. RESULTS: Compared with the obese bronchoscopy group,
      the obese US group had a significantly shorter PDT operation time (mean +/- SD,
      12.8 +/- 4.8 versus 16.2 +/- 4.4 minutes; P = .026), fewer punctures (P = .011),
      and a lesser amount of intraoperative hemorrhage (12.1 +/- 4.6 versus 16.8 +/-
      4.3 mL; P = .009). There were no significant differences in these parameters
      between the normal US and normal bronchoscopy groups. CONCLUSIONS: Ultrasound
      guided PDT significantly reduced the number of punctures and the operation time
      compared with bronchoscopy-guided PDT, and it decreased intraoperative hemorrhage
      in critically ill obese patients. Percutaneous dilatational tracheostomy with US
      guidance was a faster, safer, and more accurate method of airway management.

PMID- 29048710
TI  - Correlations Among Ultrasound-Guided Diffuse Optical Tomography, Microvessel
      Density, and Breast Cancer Prognosis.
AB  - OBJECTIVES: To investigate the correlation among ultrasound-guided diffuse
      optical tomography (DOT), microvessel density, and breast cancer prognosis.
      METHODS: Before surgery, the total hemoglobin (Hb) concentrations of 184 female
      patients with breast cancer with only a single lesion were measured. During
      follow-up, 23 patients had recurrence or metastatic disease after surgery. Among
      these patients, 18 with recurrence or metastatic disease within 3 years after
      surgery were paired with 18 patients without recurrence or metastatic disease. We
      retrospectively reviewed the pathologic sections of those 36 patients, conducted
      immunohistochemical staining, and counted the microvessel densities. Then we
      analyzed the correlation between microvessel density and total Hb, compared total
      Hb and microvessel density among breast cancers with different prognoses, and
      tested the value of DOT in predicting the prognosis of breast cancer. RESULTS:
      Microvessel density and total Hb were linearly correlated (r = 0.584; P < .001).
      Total Hb and microvessel density were significantly increased in the metastasis
      group (P = .001 and .027, respectively). A receiver operating characteristic
      curve analysis showed that at a total Hb cutoff value of 221.7 MUmol/L, the
      sensitivity, specificity, and area under the curve of DOT for predicting
      recurrence or metastasis were 0.826, 0.516, and 0.660, respectively. CONCLUSIONS:
      The total Hb concentration can reflect a tumor's blood supply. Patients with a
      high total Hb concentration and microvessel density have a higher risk for a
      poorer prognosis. Total Hb can be used as an indicator of breast cancer
      prognosis. Diffuse optical tomography can help physicians identify patients with
      a high risk of metastasis and make clinical decisions.

PMID- 29048711
TI  - Rotavirus virus-like particles (RV-VLPs) vaccines: An update.
AB  - Rotaviruses (RVs) cause over 0.2 million deaths annually and are reported to be
      the foremost cause of gastroenteritis in infants and children worldwide.
      Vaccination against RVs is the most successful and unsurpassed strategy to combat
      infection to date. Although the 2 current vaccines, Rotarix and RotaTeq, have
      dramatically reduced the disease burden, still there is a need for new vaccines.
      In this context, RV virus-like particles (RV-VLPs) represent potential vaccine
      candidates as they are noninfectious and effective nonreplicating immunogens that
      may reduce the risk of side effects related to the conventional vaccines. VLPs
      being conformationally similar to the parent virus are highly immunogenic and
      hence provide enhanced protection and better serotype coverage. In this review,
      we have highlighted the various advantages and the implications of RV-VLPs,
      discussed the general strategies employed for their production, and talked about
      the recent developments made in this regard. Overall, the review emphasizes the
      probable utility of RV-VLPs in eradicating the highly widespread RVs.

PMID- 29048713
TI  - Cucurbit[7]uril as a Supramolecular Artificial Enzyme for Diels-Alder Reactions.
AB  - The ability to mimic the activity of natural enzymes using supramolecular
      constructs (artificial enzymes) is a vibrant scientific research field. Herein,
      we demonstrate that cucurbit[7]uril (CB[7]) can catalyse Diels-Alder reactions
      for a number of substituted and unreactive N-allyl-2-furfurylamines under
      biomimetic conditions, without the need for protecting groups, yielding powerful
      synthons in previously unreported mild conditions. CB[7] rearranges the substrate
      in a highly reactive conformation and shields it from the aqueous environment,
      thereby mimicking the mode of action of a natural Diels-Alderase. These findings
      can be directly applied to the phenomenon of product inhibition observed in
      natural Diels-Alderase enzymes, and pave the way toward the development of novel,
      supramolecular-based green catalysts.

PMID- 29048712
TI  - Efficacy and safety of Nuwiq(r) (human-cl rhFVIII) in patients with severe
      haemophilia A undergoing surgical procedures.
AB  - INTRODUCTION: Haemophilia A patients are at a high risk of excess bleeding during
      surgeries. The aim of haemostatic therapy during the perioperative period is to
      normalize FVIII level perioperatively and postoperatively to maintain normal
      haemostasis until wound healing is complete. AIMS/METHODS: To examine the
      efficacy of Nuwiq(r) (simoctocog alfa, human-cl rhFVIII), a 4th generation
      recombinant FVIII produced in a human cell line, for surgical prophylaxis in
      patients with severe haemophilia A. This analysis assessed the efficacy of
      Nuwiq(r) during surgical procedures and in the postoperative period in seven
      clinical studies of previously treated patients (PTPs) with severe haemophilia A.
      RESULTS: Thirty-six patients, aged 3-55 years, received surgical prophylaxis with
      Nuwiq(r) for 60 surgeries (28 major and 32 minor). Efficacy was evaluated for 52
      surgeries (25 major and 27 minor). The success rate of Nuwiq(r) treatment was
      98.1% (51 of 52 evaluated surgeries); haemostatic efficacy was assessed as
      "excellent" or "good" in all but one major surgery (assessed as "moderate"). The
      number of infusions ranged from 1 to 19 for minor surgeries and from 3 to 76 for
      major surgeries. The median (range) daily doses were 42.0 (28.2-100.9) IU kg-1
      for minor surgeries and 69.3 (43.3-135.6) IU kg-1 for major surgeries. There were
      no serious treatment-related adverse events, and none of the patients developed
      FVIII inhibitors. CONCLUSIONS: The results of this pooled analysis show that
      Nuwiq(r) was efficacious in maintaining haemostasis during and after major and
      minor surgical procedures in PTPs with severe haemophilia A.

PMID- 29048715
TI  - One-Pot Four-Segment Ligation Using Seleno- and Thioesters: Synthesis of
      Superoxide Dismutase.
AB  - The synthesis of a peptide selenoester was efficiently carried out by the 9
      fluorenylmethoxycarbonyl (Fmoc) method using N-alkylcysteine, at the C-terminus
      of the peptide, as the N-to-S acyl shift device. The selenoester selectively
      reacted with the terminal amino group of the peptide aryl thioester in the
      presence of N,N-diisopropylethylamine and dipyridyldisulfide, thus leaving the
      aryl thioester intact. Combined with silver-ion-promoted and silver-ion-free
      thioester activation methods, a one-pot four-segment ligation was realized. The
      method was successfully used to assemble the entire sequence of superoxide
      dismutase (SOD), which is composed of 153 amino-acid residues, in one pot. After
      the folding reaction, the fully active SOD was obtained.

PMID- 29048714
TI  - High genetic risk scores for impaired insulin secretory capacity doubles the risk
      for type 2 diabetes in Asians and is exacerbated by Western-type diets.
AB  - BACKGROUND: Asians have among the highest incidence of type 2 diabetes (T2DM) in
      the world, partly due to low beta-cell function, causing them to rapidly develop
      T2DM when insulin resistant. This study tested the hypothesis that genetic
      polymorphisms are responsible for the low beta-cell function and that dietary
      factors interact with the genes to exacerbate their risk of T2DM. METHODS: We
      selected 10 genetic variants of 5 genes involved in insulin secretion (CDKAL1,
      KCNQ1, IDE, HHEX, and ABCA1) from the genome-wide association studies to
      calculate the genetic risk scores (GRSs) in 8842 Korean adults in the
      Ansan/Ansung cohort in the Korean Genome Epidemiology Study. The genetic risk
      score were divided into low, medium, and high groups, and the association between
      T2DM and the genetic risk score was measured using logistic regression. We also
      analysed the interaction between the genetic risk score and the nutrition
      intakes. RESULTS: The individual genetic variants were positively associated with
      T2DM even when adjusted for covariates. Individuals with medium and high genetic
      risk score had higher T2DM risk by 1.68 and 2.17 folds compared to those with the
      low genetic risk score after adjusting for covariates. The increased risk was
      mainly associated with lower HOMA-B, an indicator of insulin secretion capacity,
      but not HOMA-IR, an indicator of insulin resistance. Subjects with high
      carbohydrate intakes and a medium genetic risk score did not have a higher risk
      of T2DM, and the risk was partially mitigated in the high genetic risk score
      group. CONCLUSION: Seventy-two percent of the Korean population had either medium
      or high genetic risk scores for impaired insulin secretion, which approximately
      doubled their risk of type 2 diabetes, and the risk was exacerbated by consuming
      a low carbohydrate Western-style diets.

PMID- 29048716
TI  - Visible-Light-Driven Palladium-Catalyzed Radical Alkylation of C-H Bonds with
      Unactivated Alkyl Bromides.
AB  - Reported herein is a novel visible-light photoredox system with Pd(PPh3 )4 as the
      sole catalyst for the realization of the first direct cross-coupling of C(sp3 )-H
      bonds in N-aryl tetrahydroisoquinolines with unactivated alkyl bromides.
      Moreover, intra- and intermolecular alkylations of heteroarenes were also
      developed under mild reaction conditions. A variety of tertiary, secondary, and
      primary alkyl bromides undergo reaction to generate C(sp3 )-C(sp3 ) and C(sp2 )
      C(sp3 ) bonds in moderate to excellent yields. These redox-neutral reactions
      feature broad substrate scope (>60 examples), good functional-group tolerance,
      and facile generation of quaternary centers. Mechanistic studies indicate that
      the simple palladium complex acts as the visible-light photocatalyst and radicals
      are involved in the process.

PMID- 29048717
TI  - Unexpected Crystallization Patterns of Zinc Boron Imidazolate Framework ZBIF-1:
      NMR Crystallography of Integrated Metal-Organic Frameworks.
AB  - Framework materials, that is, metal-organic frameworks (MOFs) and inorganic
      frameworks (zeolites), are porous systems with regular structures that provide
      valuable properties suitable for sorption, catalysis, molecular sieving, and so
      on. Herein, an efficient, experimental/computational strategy is presented that
      allows detailed characterization of a polycrystalline MOF system, namely, zinc
      boron imidazolate framework ZBIF-1, with two integrated unit cells on the atomic
      resolution level. Although high-resolution 1 H, 11 B, 13 C, and 15 N MAS NMR
      spectra provide valuable structural information on the coexistence of two
      distinct asymmetric units in the investigated system, an NMR crystallography
      approach combining X-ray powder diffraction, solid-state NMR spectroscopy, and
      DFT calculations allowed the exact structure of the secondary crystalline phase
      to be firmly defined and, furthermore, the mutual interconnectivity of the two
      crystalline frameworks to be resolved. Thus, this study shows the versatility and
      efficiency of solid-state NMR crystallography for the investigation of the wide
      family of MOF materials with their extensive structural complexity.

PMID- 29048718
TI  - Azido-Functionalized 5' Cap Analogues for the Preparation of Translationally
      Active mRNAs Suitable for Fluorescent Labeling in Living Cells.
AB  - The 7-methylguanosine (m7 G) cap structure is a unique feature present at the 5'
      ends of messenger RNAs (mRNAs), and it can be subjected to extensive
      modifications, resulting in alterations to mRNA properties (e.g. translatability,
      susceptibility to degradation). It also can provide molecular tools to study mRNA
      metabolism. We developed new mRNA 5' cap analogues that enable the site-specific
      labeling of RNA at the 5' end using strain-promoted azide-alkyne cycloaddition
      (SPAAC) without disrupting the basic function of mRNA in protein biosynthesis.
      Some of these azide-functionalized compounds are equipped with additional
      modifications to augment mRNA properties. The application of these tools was
      demonstrated by labeling translationally active mRNAs in living cells.

PMID- 29048719
TI  - The First Boron-Tellurium Double Bond: Direct Insertion of Heavy Chalcogens into
      a Mn=B Double Bond.
AB  - The base-stabilized borylene [Cp(OC)2 Mn=BtBu(IMe)] readily reacts with elemental
      chalcogens in an insertion reaction that yields borachalcone complexes [Cp(OC)2
      Mn-E=BtBu(IMe)] (E=S, Se, Te). The tellurium example features the first double
      bond between boron and tellurium, making Te the heaviest main-group element to
      make multiple bonds with boron. This unprecedented interaction has been fully
      investigated both experimentally and computationally.

PMID- 29048720
TI  - Controllable Modular Growth of Hierarchical MOF-on-MOF Architectures.
AB  - Fabrication of hybrid MOF-on-MOF heteroarchitectures can create novel and
      multifunctional platforms to achieve desired properties. However, only MOFs with
      similar crystallographic parameters can be hybridized by the classical epitaxial
      growth method (EGM), which largely suppressed its applications. A general
      strategy, called internal extended growth method (IEGM), is demonstrated for the
      feasible assembly of MOFs with distinct crystallographic parameters in an MOF
      matrix. Various MOFs with diverse functions could be introduced in a modular MOF
      matrix to form 3D core-satellite pluralistic hybrid system. The number of
      different MOF crystals interspersed could be varied on demand. More importantly,
      the different MOF crystals distributed in individual domains could be used to
      further incorporate functional units or enhance target functions.

PMID- 29048721
TI  - The immune profile induced is crucial to determine the effects of
      immunocastration over gonadal function, fertility, and GnRH-I expression.
AB  - PROBLEM: Immunocastration or vaccination against the GnRH-I hormone is a
      promising alternative to reproductive control in different animal species. Given
      the low immunogenicity of this hormone, the use of adjuvants becomes necessary.
      METHOD OF STUDY: This study evaluated the effects of three adjuvants that induce
      different immune response profiles over gonadal function, fertility, and
      expression of GnRH-I. Female mice (n = 6) were vaccinated at days 1 and 30 with a
      recombinant antigen for immunocastration and different adjuvants that induced
      preferentially Th1/Th2, Th2, and Th1 immune profiles. RESULTS: Th1/Th2 response
      is the most efficient to block reproductive activity in vaccinated animals,
      reducing the number of luteal bodies and pre-ovulatory follicles. Th2 and Th1/Th2
      responses induced an increase in GnRH-I at the hypothalamus. CONCLUSION: The
      immune profile induced by different adjuvants is essential on the effects over
      fertility, gonadal function, and hypothalamic GnRH-I expression in
      immunocastrated animals.

PMID- 29048722
TI  - Fractures and ventilator dependence in neonates: Is the use of bisphosphonates an
      appropriate consideration?

PMID- 29048723
TI  - The story continues: an overview of the 'Dissertations into Practice' feature.
AB  - The 'Dissertations into practice' feature began life in March 2012 with a dual
      aim: to encourage students, recent graduates and new professionals to write for
      publication and to highlight the impact of student research on policy and
      practice. This article reflects on the initiative and demonstrates that it has
      been extremely successful in achieving both aims. It highlights the diverse range
      of contributions to the feature so far and proves that student research can and
      does influence policy and practice. It also demonstrates that, with the right
      encouragement and support, students are willing and able to write for academic
      publication and that they gain a lot from the experience. A. M.

PMID- 29048724
TI  - Longitudinal perspectives on the psychosis spectrum in 22q11.2 deletion syndrome.
AB  - The prevalence of psychotic disorders in individuals with 22q11.2 Deletion
      Syndrome (22q11DS) reaches 25-35% in young adulthood and may provide a
      neurogenetic model for clinical risk of psychotic disorders in the general
      population. This review focuses on prospective longitudinal studies in 22q11DS,
      which capture fluctuations in psychosis symptoms over time and may provide
      insights into potential demographic, clinical, cognitive, and neuroimaging
      predictors of psychosis-spectrum outcomes in the general population. Findings are
      compared and contrasted with those from idiopathic psychosis-spectrum
      populations. Onset of psychotic disorders in 22q11DS can occur over a wide range
      of ages, peaking in late adolescence. Symptoms may be gradually progressive or
      episodic in nature, highlighting the importance and challenge of risk and
      resilience prediction models. Converging results suggest that psychosis-spectrum
      outcomes in 22q11DS are predicted by lower baseline functioning, higher baseline
      psychosis-spectrum symptoms, presence of mood disturbance or anxiety, and lower
      baseline and subsequent decline in global measures of cognition. Predictors of
      transition to threshold psychotic disorders and ages of onset are similar in
      idiopathic clinical risk. They also share similarly global cognitive deficits,
      but not to the same extent as in 22q11DS. While neuroimaging studies in
      idiopathic clinical risk suggest loss of prefrontal gray matter, there is no
      consistent evidence yet emerging in the limited literature in 22q11DS.
      Interventional efforts in 22q11DS aimed at halting progression to psychosis or
      mitigating outcomes in early psychosis may be best implemented during the
      adolescent age range. Collaborative longitudinal efforts may help to address
      existing gaps in our understanding.

PMID- 29048725
TI  - Biallelicframeshift mutation in RIN2 in a patient with intellectual disability
      and cataract, without RIN2 syndrome.

PMID- 29048726
TI  - Trends in inequalities in child stunting in South Asia.
AB  - We analysed socio-economic inequalities in stunting in South Asia and
      investigated disparities associated with factors at the individual, caregiver,
      and household levels (poor dietary diversity, low maternal education, and
      household poverty). We used time-series analysis of data from 55,459 children
      ages 6-23 months from Demographic and Health Surveys in Bangladesh, India, Nepal,
      and Pakistan (1991-2014). Logistic regression models, adjusted for age, sex,
      birth order, and place of residency, examined associations between stunting and
      multiple types of socio-economic disadvantage. All countries had high stunting
      rates. Bangladesh and Nepal recorded the largest reductions-2.9 and 4.1
      percentage points per year, respectively-compared to 1.3 and 0.6 percentage
      points in India and Pakistan, respectively. Socio-economic adversity was
      associated with increased risk of stunting, regardless of disadvantage type. Poor
      children with inadequate diets and with poorly educated mothers experienced
      greater risk of stunting. Although stunting rates declined in the most deprived
      groups, socio-economic differences were largely preserved over time and in some
      cases worsened, namely, between wealth quintiles. The disproportionate burden of
      stunting experienced by the most disadvantaged children and the worsening
      inequalities between socio-economic groups are of concern in countries with
      substantial stunting burdens. Closing the gap between best and worst performing
      countries, and between most and least disadvantaged groups within countries,
      would yield substantial improvements in stunting rates in South Asia. To do so,
      greater attention needs to be paid to addressing the social, economic, and
      political drivers of stunting with targeted efforts towards the populations
      experiencing the greatest disadvantage and child growth faltering.

PMID- 29048727
TI  - Mutations of KIF5C cause a neurodevelopmental disorder of infantile-onset
      epilepsy, absent language, and distinctive malformations of cortical development.
AB  - The clinical diagnosis of malformations of cortical development (MCDs) is often
      challenging due to the complexity of the brain malformation by neuroimaging, the
      rarity of individual malformation syndromes, and the rapidly evolving genetic
      landscape of these disorders facilitated with the use of Next Generation
      Sequencing (NGS) methods. While the clinical and molecular diagnosis of severe
      cortical malformations, such as classic lissencephaly, is often straightforward,
      the diagnosis of more subtle and complex types of cortical malformations, such as
      pachygyria and polymicrogyria (PMG), can be more challenging due to limited
      knowledge regarding their genetic etiologies. Here, we report two individuals
      with the same de novo KIF5C mutation who present with subtle MCDs, early onset
      epilepsy and significant neurodevelopmental and behavioral issues including
      absent language. Our data, combined with the limited literature on KIF5C
      mutations, to date, support that KIF5C mutations are associated with a
      neurodevelopmental disorder characterized by infantile onset epilepsy, and subtle
      but recognizable types of brain malformations. We also show that the spectrum of
      KIF5C mutations is narrow, as five out of the six identified individuals have
      mutations affecting amino acid Glu237. Therefore, the identification of the
      clinical and neuroimaging features of this disorder may strongly facilitate rapid
      and efficient molecular diagnosis.

PMID- 29048728
TI  - Cytokeratin7 expression in histologic and cytologic specimens of cystic neck
      metastasis from HPV positive squamous cell carcinoma of the tonsil: A case
      report.
AB  - The majority of cystic squamous cell carcinomas (SCCs) of the neck have been
      shown to be metastatic tumors from tonsillar SCCs associated with high-risk human
      papillomavirus (HR HPV). Recent studies have demonstrated cytokeratin (CK)7
      involvement in the development of HPV positive SCC, but no report has been issued
      on its simultaneous expression in primary tonsillar and metastatic tumor with
      cystic change. We present a case of HPV positive tonsillar SCC of a 42-year-old
      male that initially manifested as a cystic neck mass expressing CK7, CK19, and
      p16 in primary and metastatic tumors. Immunohistochemical examination revealed
      diffuse CK19 and p16 expression, and patchy CK7 expression in the solid
      components of primary and metastatic tumors. However, in cystic components of
      metastatic tumors the expression of CK7 and CK19 was preserved but p16 expression
      was absent, which was consistent with immunocytochemical findings of fine-needle
      aspirates from cystic neck mass. In immunocytochemistry performed on aspirates of
      a branchial cleft cyst for the comparison of cystic SCC and benign cyst, CK19
      staining was positive but CK7 and p16 staining was negative. These results
      suggest that CK7 immunocytochemistry on aspirated material from cystic neck mass
      may be a useful adjunct for distinguishing cystic metastasis of tonsillar SCC
      from branchial cleft cyst, although a larger scale study would be required.

PMID- 29048729
TI  - Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21
      with partial monosomy 21q22.3.
AB  - Inverted isodicentric chromosome 21 is a rare form of chromosomal rearrangement
      that may result in trisomy 21; sometimes this rearrangement may also lead to
      segmental monosomy of the terminal long arm of chromosome 21. In this report, we
      describe the prenatal diagnosis and neonatal follow-up of a child with a
      paternally derived, de novo isodicentric chromosome 21 and a concurrent ~1.2 Mb
      deletion of the 21q22.3 region [46,XX,idic(21)(q22.3)]. This child presented with
      unusual phenotype of Down syndrome and additional defects including esophageal
      atresia and tethered cord syndrome. The resulting phenotype in this infant might
      be a coalescence of the partial trisomy and monosomy 21, as well as homozygosity
      for idic (21). The utilization of chromosomal microarray in this case enabled
      accurate characterization of a rare chromosome abnormality, potentially
      contributes to future phenotype-genotype correlation and produced evidence for a
      molecular mechanism underlying this rearrangement.

PMID- 29048730
TI  - Bronchial oncocytosis: An incidental finding in ultrasound-guided transbronchial
      fine-needle aspiration cytology.

PMID- 29048731
TI  - Caesarean delivery and anaemia risk in children in 45 low- and middle-income
      countries.
AB  - Caesarean delivery (CD) may reduce placental transfusion and cause poor iron
      related haematological indices in the neonate. We aimed to explore the
      association between CD and anaemia in children aged <5 years utilising data from
      Demographic and Health Surveys conducted between 2005 and 2015 in 45 low- and
      middle-income countries (N = 132,877). We defined anaemia categories based on
      haemoglobin levels, analysed each country's data separately using propensity
      score weighting, pooled the country-specific odds ratios (ORs) using random
      effects meta-analysis, and performed meta-regression to determine whether the
      association between CD and anaemia varies by national CD rate, anaemia
      prevalence, and gross national income. Individual-level CD was not associated
      with any anaemia (OR 0.95, 95% confidence interval (CI) [0.86, 1.06]; I2  =
      40.2%), mild anaemia (OR 0.91, 95% CI [0.81, 1.02]; I2  = 24.8%), and
      moderate/severe anaemia (OR 0.97, 95% CI [0.85, 1.11]; I2  = 47.7%). CD tended to
      be positively associated with moderate/severe anaemia in upper middle-income
      countries and negatively associated with mild anaemia in lower middle-income
      countries; however, meta-regression did not detect any variation in the
      association between anaemia and CD by the level of income, CD rate, and anaemia
      prevalence. In conclusion, there was no evidence for an association between CD
      and anaemia in children younger than 5 years in low- and middle-income countries.
      Our conclusions were consistent when we looked at only countries with CD rate
      >15% with data stratified by individual-level wealth status and type of health
      facility of birth.

PMID- 29048732
TI  - Chemical Stimulus-responsive Folding and Unfolding of a Dendrimeric Assembly.
AB  - A dendrimeric trimer undergoes folding and unfolding in response to a chemical
      stimulus. The trimer of interest contains a central dendrimer with a butadiyne
      linked zinc porphyrin dimer ((ZnP)2 ) core, in addition to two terminal
      dendrimers with zinc porphyrin (ZnP) cores. The obtained absorption spectra
      indicate that the unfolded form is the exclusive conformer in chloroform, while
      the addition of 1,4-diazabicyclo[2.2.2]octane (DABCO) in chloroform leads to
      transformation from the unfolded to the folded structure containing two DABCO
      units per trimer; the folded structure originates from the cross-linking of
      (ZnP)2 and ZnP with DABCO. Moreover, the addition of excess DABCO promotes the
      generation of the unfolded structure containing four DABCO units.

PMID- 29048733
TI  - Cytology and high risk HPV testing in cervical cancer screening program: Outcome
      of 3-year follow-up in an academic institute.
AB  - BACKGROUND: Combination of cervical cytology and high-risk human papillomavirus
      (HR-HPV) testing, co-testing, has been increasingly used in screening cervical
      cancers. The present study summarized the outcome of co-testing by reviewing 3
      year clinical and pathological follow-up information. METHODS: Patients were
      retrospectively identified via computerized search and were grouped based on the
      cytologic diagnosis and HR-HPV status as negative for intraepithelial lesion or
      malignancy (NILM)/HPV-, NILM/HPV+, atypical squamous cells of undetermined
      significance (ASC-US)/HPV-, ASC-US/HPV+, low grade squamous intraepithelial
      lesion (LSIL)/HPV-, LSIL/HPV+, atypical squamous cells, cannot exclude high grade
      squamous intraepithelial lesion (ASC-H)/HPV-, ASC-H/HPV+, high grade squamous
      intraepithelial lesion (HSIL)/HPV-, and HSIL/HPV+. The patients' pertinent past
      medical history and follow-up information were analyzed. RESULTS: During 3-year
      follow-up period, histologically proven HSIL was found in 5 of 1565 (0.3%)
      patients with NILM/HPV-, 7 of 141 (5.0%) with NILM/HPV+, 2 of 502 (0.4%) with ASC
      US/HPV-, 30 of 274 (10.9%) with ASC-US/HPV+, 1 of 81 (1.2%) with LSIL/HPV-, 28 of
      159 (17.6%) with LSIL/HPV+, 3 of 18 (16.7%) with ASC-H/HPV-, 34 of 69 (49.3%)
      with ASC-H/HPV+, 7 of 7 (100%) with HSIL/HPV-, and 35 of 56 (62.5%) HSIL/HPV+. In
      reviewing 12 HSIL cases that were originally diagnosed as NILM, 7 remained as
      NILM, and the other 5 were reclassified as 1 HSIL, 1 ASC-H, and 3 ASC-US,
      respectively. In 18 HSIL cases with negative HR-HPV, 12 patients had a prior
      history of positive HR-HPV testing and/or positive p16 IHC stain in the follow-up
      cervical biopsy. CONCLUSION: HR-HPV testing plays an important role in cervical
      cancer screening by identifying HSIL in patients with ASC-US, LSIL, and NILM. Co
      testing is an optimal method to identifying the patients with higher risk for
      developing cervical abnormalities.

PMID- 29048734
TI  - Imidazolium-Based Ionic Liquids as Efficient Reagents for the C-O Bond Cleavage
      of Lignin.
AB  - The demethylation of lignin in ionic liquids (ILs) was investigated by using pure
      lignin model monomers and dimers together with dioxane-isolated lignins from
      poplar, miscanthus, and maize. Different methylimidazolium ILs were compared and
      the samples were treated with two different heating processes: microwave
      irradiation and conventional heating in a sealed tube. The conversion yield and
      influence of the treatment on the lignin structure were assessed by 31 P NMR
      spectroscopy, size-exclusion chromatography, and thioacidolysis. The acidic
      methylimidazolium IL [HMIM]Br was shown to be an effective combination of solvent
      and reagent for the demethylation and depolymerization of lignin. The relatively
      mild reaction conditions, the clean work-up, and the ability to reuse the IL
      makes the described procedure an attractive and new green method for the
      conversion of lignin to produce phenol-rich lignin oligomers.

PMID- 29048735
TI  - 6-Hydroxydopamine induces brain vascular endothelial inflammation.
AB  - Disruption of the blood-brain barrier associated with endothelial dysfunction is
      an important hallmark of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is
      a synthetic dopamine derivate often used to model PD as it results in retrograde
      degeneration of striatal dopaminergic (DA) terminals. Presently, the effects of 6
      OHDA on endothelial dysfunction remain unknown. Using a 6-OHDA rodent model of
      PD, we found that administration of 6-OHDA could increase the expression of
      endothelial adhesion molecules, such as intercellular adhesion molecule 1 (ICAM
      1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin. An in vitro study
      displayed that treatment with 6-OHDA increased the release of these molecules in
      human brain microvascular endothelial cells in a dose-dependent manner.
      Correspondingly, 6-OHDA significantly increased attachment of THP-1 monocytes to
      brain endothelial cells. In addition, real-time polymerase chain reaction and
      enzyme-linked immunosorbent assay results indicated that 6-OHDA elevated the
      production of proinflammatory cytokines, such as interleukin-1beta, interleukin
      6, and tumor necrosis factor-alpha. Furthermore, 6-OHDA treatment increased the
      expression of cyclooxygenase-2 and inducible nitric oxide synthase, as well as
      the production of prostaglandin E2 and nitric oxide. Importantly, 6-OHDA elevated
      the transcriptional activity of NF-kB by increasing the phosphorylation,
      degradation, and subsequent nuclear translocation of p65. Mechanistically, the
      angiotensin II type 1 receptor was found to mediate 6-OHDA-induced endothelial
      dysfunction. Our findings suggest that 6-OHDA-induced endothelial inflammation
      may play an important role in the pathogenesis of PD. (c) 2017 IUBMB Life,
      69(11):887-895, 2017.

PMID- 29048737
TI  - Insulin-like growth factor-2 mRNA-binding protein 3 as a novel prognostic
      biomarker for acral lentiginous melanoma.

PMID- 29048736
TI  - Novel recessive PDZD7 biallelic mutations in two Chinese families with non
      syndromic hearing loss.
AB  - Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous
      genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL.
      Biallelic mutations in the PDZD7 gene have been reported in two German families,
      four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on
      ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families,
      each of which had two affected siblings, were included in this study. The
      families underwent target region capture and high-throughput sequencing to
      analyze the exonic, splice-site, and intronic sequences of 128 genes.
      Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese
      families segregating with apparent ARNSHL, who had been previously excluded for
      variants in the common deafness genes GJB2 and SLC26A4, were subjected to
      screening for candidate mutations. We identified a novel homozygous missense
      mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations
      (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the
      first report to identify PDZD7 as an ARNSHL-associated gene in the Chinese
      population. Our finding could expand the pathogenic spectrum and strengthens the
      clinical diagnostic role of the PDZD7 gene in ARNSHL patients.

PMID- 29048738
TI  - Seasonality of hair loss: a time series analysis of Google Trends data 2004-2016.

PMID- 29048739
TI  - Pharmacotherapy for social anxiety disorder (SAnD).
AB  - BACKGROUND: Recognition is growing that social anxiety disorder (SAnD) is a
      chronic and disabling disorder, and data from early trials demonstrate that
      medication may be effective in its treatment. This systematic review is an update
      of an earlier review of pharmacotherapy of SAnD. OBJECTIVES: To assess the
      effects of pharmacotherapy for social anxiety disorder in adults and identify
      which factors (methodological or clinical) predict response to treatment. SEARCH
      METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials
      Register (CCMDCTR-Studies and CCMDCTR-References) to 17 August 2015. The CCMDCTR
      contains reports of relevant RCTs from MEDLINE (1950-), Embase (1974-), PsycINFO
      (1967-) and CENTRAL (all years). We scanned the reference lists of articles for
      additional studies. We updated the search in August 2017 and placed additional
      studies in Awaiting Classification, these will be incorporated in the next
      version of the review, as appropriate. SELECTION CRITERIA: We restricted studies
      to randomised controlled trials (RCTs) of pharmacotherapy versus placebo in the
      treatment of SAnD in adults. DATA COLLECTION AND ANALYSIS: Two authors (TW and
      JI) assessed trials for eligibility and inclusion for this review update. We
      extracted descriptive, methodological and outcome information from each trial,
      contacting investigators for missing information where necessary. We calculated
      summary statistics for continuous and dichotomous variables (if provided) and
      undertook subgroup and sensitivity analyses. MAIN RESULTS: We included 66 RCTs in
      the review (> 24 weeks; 11,597 participants; age range 18 to 70 years) and 63 in
      the meta-analysis. For the primary outcome of treatment response, we found very
      low-quality evidence of treatment response for selective serotonin reuptake
      inhibitors (SSRIs) compared with placebo (number of studies (k) = 24, risk ratio
      (RR) 1.65; 95% confidence interval (CI) 1.48 to 1.85, N = 4984). On this outcome
      there was also evidence of benefit for monoamine oxidase inhibitors (MAOIs) (k =
      4, RR 2.36; 95% CI 1.48 to 3.75, N = 235), reversible inhibitors of monoamine
      oxidase A (RIMAs) (k = 8, RR 1.83; 95% CI 1.32 to 2.55, N = 1270), and the
      benzodiazepines (k = 2, RR 4.03; 95% CI 2.45 to 6.65, N = 132), although the
      evidence was low quality. We also found clinical response for the anticonvulsants
      with gamma-amino butyric acid (GABA) analogues (k = 3, RR 1.60; 95% CI 1.16 to
      2.20, N = 532; moderate-quality evidence). The SSRIs were the only medication
      proving effective in reducing relapse based on moderate-quality evidence. We
      assessed tolerability of SSRIs and the serotonin and norepinephrine reuptake
      inhibitor (SNRI) venlafaxine on the basis of treatment withdrawal; this was
      higher for medication than placebo (SSRIs: k = 24, RR 2.59; 95% CI 1.97 to 3.39,
      N = 5131, low-quality evidence; venlafaxine: k = 4, RR 3.23; 95% CI 2.15 to 4.86,
      N = 1213, moderate-quality evidence), but there were low absolute rates of
      withdrawal for both these medications classes compared to placebo. We did not
      find evidence of a benefit for the rest of the medications compared to
      placebo.For the secondary outcome of SAnD symptom severity, there was benefit for
      the SSRIs, the SNRI venlafaxine, MAOIs, RIMAs, benzodiazepines, the antipsychotic
      olanzapine, and the noradrenergic and specific serotonergic antidepressant
      (NaSSA) atomoxetine in the reduction of SAnD symptoms, but most of the evidence
      was of very low quality. Treatment with SSRIs and RIMAs was also associated with
      a reduction in depression symptoms. The SSRIs were the only medication class that
      demonstrated evidence of reduction in disability across a number of domains.We
      observed a response to long-term treatment with medication for the SSRIs (low
      quality evidence), for the MAOIs (very low-quality evidence) and for the RIMAs
      (moderate-quality evidence). AUTHORS' CONCLUSIONS: We found evidence of treatment
      efficacy for the SSRIs, but it is based on very low- to moderate-quality
      evidence. Tolerability of SSRIs was lower than placebo, but absolute withdrawal
      rates were low.While a small number of trials did report treatment efficacy for
      benzodiazepines, anticonvulsants, MAOIs, and RIMAs, readers should consider this
      finding in the context of potential for abuse or unfavourable side effects.

PMID- 29048740
TI  - Thyroid hormone fluctuations indicate a thermoregulatory function in both a
      tropical (Alouatta palliata) and seasonally cold-habitat (Macaca fuscata)
      primate.
AB  - Thyroid hormones boost animals' basal metabolic rate and represent an important
      thermoregulatory pathway for mammals that face cold temperatures. Whereas the
      cold thermal pressures experienced by primates in seasonal habitats at high
      latitudes and elevations are often apparent, tropical habitats also display
      distinct wet and dry seasons with modest changes in thermal environment. We
      assessed seasonal and temperature-related changes in thyroid hormone levels for
      two primate species in disparate thermal environments, tropical mantled howlers
      (Alouatta palliata), and seasonally cold-habitat Japanese macaques (Macaca
      fuscata). We collected urine and feces from animals and used ELISA to quantify
      levels of the thyroid hormone triiodothyronine (fT3 ). For both species, fT3
      levels were significantly higher during the cooler season (wet/winter),
      consistent with a thermoregulatory role. Likewise, both species displayed greater
      temperature deficits (i.e., the degree to which animals warm their body
      temperature relative to ambient) during the cooler season, indicating greater
      thermoregulatory pressures during this time. Independently of season, Japanese
      macaques displayed increasing fT3 levels with decreasing recently experienced
      maximum temperatures, but no relationship between fT3 and recently experienced
      minimum temperatures. Howlers increased fT3 levels as recently experienced
      minimum temperatures decreased, although demonstrated the opposite relationship
      with maximum temperatures. This may reflect natural thermal variation in howlers'
      habitat: wet seasons had cooler minimum and mean temperatures than the dry
      season, but similar maximum temperatures. Overall, our findings support the
      hypothesis that both tropical howlers and seasonally cold-habitat Japanese
      macaques utilize thyroid hormones as a mechanism to boost metabolism in response
      to thermoregulatory pressures. This implies that cool thermal pressures faced by
      tropical primates are sufficient to invoke an energetically costly and relatively
      longer-term thermoregulatory pathway. The well-established relationship between
      thyroid hormones and energetics suggests that the seasonal hormonal changes we
      observed could influence many commonly studied behaviors including food choice,
      range use, and activity patterns.

PMID- 29048741
TI  - Diagnostic value of urinary CXCL10 as a biomarker for predicting Hunner type
      interstitial cystitis.
AB  - AIM: To investigate the feasibility of chemokines and cytokines potentially
      elevated in the bladder tissue of Hunner type interstitial cystitis (HIC) as
      urinary markers for distinguishing HIC from non-Hunner type interstitial cystitis
      (NHIC) METHODS: Urine specimens were collected from 41 HIC patients, 25 NHIC
      patients, and 31 healthy volunteers (control). The supernatants of urine
      specimens were subjected to ELISA kits for measurements of 10 cytokines and
      chemokines, whose gene expression was known to be elevated in HIC bladder tissue.
      Urinary levels normalized by urinary creatinine (Cr) concentration were compared
      among three groups. Efficiency in differentiating IC and IC subtypes was explored
      by ROC analysis. The correlation of marker levels with symptom severity, assessed
      by O'Leary-Sant's symptom index (OSSI) and problem index (OSPI), was examined.
      RESULTS: The urinary levels of CXCL10 and NGF were significantly higher in HIC
      than NHIC. CXCL10 and NGF differentiated HIC against NHIC with AUC of 0.78 and
      0.68, respectively. Combination of CXCL10 and NGF levels yielded an AUS of 0.81.
      The CXCL10 cut-off of 53.2 pg/mg Cr had sensitivity of 46.1%, specificity of
      93.7%, positive predictive value of 97.7%, and negative predictive value of
      60.0%. The urinary level of other cytokines showed no significant difference
      between HIC and NHIC. Significant correlation with symptoms was detected for
      CXCL10 alone. CONCLUSION: The results suggested that increased urinary level of
      CXCL10 combined with or without high NGF level could be a promising supplementary
      biomarker for differentiating HIC from NHIC with modest sensitivity and high
      specificity.

PMID- 29048742
TI  - Permanent neonatal diabetes caused by abnormalities in chromosome 6q24.
AB  - BACKGROUND: Methylation defects at chromosome 6q24 usually induce transient
      neonatal diabetes mellitus. There are few reports of permanent neonatal diabetes
      mellitus caused by abnormalities of 6q24. We report the first case of permanent
      neonatal diabetes mellitus to be associated with confirmed methylation defects at
      chromosome 6q24. CASE REPORT: A baby girl, small for her gestational age, was
      found to have high blood glucose 1 day after birth, with no systematic congenital
      anomalies. She showed no remission of diabetes and has hitherto been reliant on
      insulin (now aged of 5.5 years), which supports a diagnosis of permanent neonatal
      diabetes mellitus. The single nucleotide polymorphism array and highly
      polymorphic short tandem repeat analysis identified paternal uniparental disomy
      of chromosome 6, and a genome-wide analysis ruled out mutations in coding and non
      coding regions. CONCLUSION: This report expands the varieties of neonatal
      diabetes known to be induced by methylation defects at chromosome 6q24, and
      suggests that the diagnostic evaluation of permanent neonatal diabetes mellitus
      should be expanded to include testing for 6q24.

PMID- 29048743
TI  - Menopause is associated with impaired responsiveness of involuntary pelvic floor
      muscle contractions to sudden intra-abdominal pressure rise in women with pelvic
      floor symptoms: A retrospective study.
AB  - AIMS: To explore the effect of menopause on the movements of the bladder neck and
      genital hiatus during involuntary and voluntary pelvic floor muscle (PFM)
      contractions among women with pelvic floor symptoms. METHODS: The data of 162
      premenopausal and 215 postmenopausal women were retrospectively analyzed. The
      investigation encompassed clinical interview, pelvic examination, and four
      dimensional ultrasound. The ultrasound manifestations of the bladder neck and
      genital hiatus during involuntary and voluntary PFM contractions were assessed
      during coughing and maximal squeezing. The bladder neck location, genitohiatal
      size, and genitohiatal location were evaluated with bladder neck distance (BND)
      and bladder neck angle (BNA), genitohiatal dimension (GHD) and genitohiatal area
      (GHAR), as well as genitohiatal angle (GHA), respectively. RESULTS: From resting
      to coughing, postmenopausal women exhibited a more caudodorsal bladder neck
      movement (changes in BND/BNA, premenopausal vs. postmenopausal women: -0.91 +/-
      1.22 cm/-12 +/- 47 degrees  vs. -0.48 +/- 0.83 cm/11 +/- 38 degrees , P < 0.001),
      less genitohiatal size reduction (changes in GHD/GHAR, premenopausal vs.
      postmenopausal women: -1.38 +/- 2.15 cm/-5.5 +/- 8.4 cm2 vs. -0.46 +/- 1.68 cm/
      1.9 +/- 7.6 cm2 , P < 0.001), and less cranioventral genitohiatal movement
      (changes in GHA, premenopausal vs. postmenopausal women: -33 +/- 63 degrees  vs. 
      11 +/- 43 degrees , P < 0.001) than premenopausal women. Premenopausal and
      postmenopausal women demonstrated comparable ultrasound manifestations of the
      bladder neck and genital hiatus during maximal squeezing. CONCLUSIONS: For women
      with pelvic floor symptoms, menopause is associated with impaired responsiveness
      of involuntary PFM contractions to sudden intra-abdominal pressure rise but not
      with voluntary PFM contractions.

PMID- 29048746
TI  - Long-term occurrence of secondary compartment pelvic organ prolapse after open
      mesh sacrocolpopexy for symptomatic prolapse.
AB  - AIMS: To report on the long-term occurrence of secondary compartment pelvic organ
      prolapse (POP) after open mesh sacrocolpopexy (MSC). METHODS: A prospectively
      maintained, IRB-approved database of non-neurogenic women with symptomatic triple
      compartment POP who underwent open MSC between 1999 and 2011 and had a 1-year
      minimum follow-up was reviewed. Length of follow-up was categorized as:
      intermediate (1-3 yr), late (3-5 yr), and very late (>5 yr). Demographic data,
      history of POP repairs, exam with Baden-Walker grading, validated questionnaires
      (Urogenital Distress Inventory short form [UDI-6], QoL), and outcomes at each
      follow-up visit were recorded. Failure was defined by either secondary
      compartment prolapse recurrence (BW > 2) on examination at the last visit or re
      operation for POP. RESULTS: Out of sixty-eight, sixty-one women met study
      criteria. Mean age was 66 +/- 11, mean BMI 26.1 +/- 4.5, mean parity 2.8 +/- 1.4
      and cohort was mostly Caucasian. --Eighty seven percent had prior hysterectomy
      and 72% had prior POP repair. Mean follow-up was 6.8 +/- 3.9 years with over 75%
      in the late or very late categories. There were 4/61 (7%) clinical failures, 3 of
      which underwent surgical repair (2 anterior and 1 posterior compartment repair)
      at 2-12 year interval post-MSC. Mean changes between baseline and last visit UDI
      6, QoL, and BW prolapse grade trended favorably. CONCLUSIONS: Following open MSC,
      the rate of secondary prolapse compartment failure was found low at very long
      term follow-up.

PMID- 29048745
TI  - Inhibition of yeast-to-filamentous growth transitions in Candida albicans by a
      small molecule inducer of mammalian apoptosis.
AB  - The opportunistic fungal pathogen of humans Candida albicans is able to grow in
      different morphological forms such as round or oval yeasts and filamentous hyphae
      and pseudohyphae. Morphogenesis, the ability to switch between the yeast and
      filamentous growth forms, is important for adapting to new microenvironments in
      the human host and for pathogenesis. The molecular pathways governing
      morphogenesis are complex and incompletely understood. Previously, we identified
      several small organic molecules that specifically inhibit the initiation of
      hyphal growth in C. albicans without affecting cell viability or budded growth.
      One molecule from that screen is known to induce apoptosis in mammalian cells. In
      this study, we have screened additional inducers of mammalian apoptosis and
      identified BH3I-1, as well as several structural derivatives of BH3I-1, that act
      as specific inhibitors of morphogenesis under a variety of environmental
      conditions. Chemical epistasis experiments suggest that BH3I-1 acts downstream of
      the hypha-specific gene regulators Rfg1, Nrg1 and Ume6.

PMID- 29048747
TI  - Association between gestational diabetes mellitus exposure and childhood
      adiposity is not substantially explained by offspring genetic risk of obesity.
AB  - AIM: To examine the extent to which offspring obesity-associated genetic risk
      explains the association between gestational diabetes mellitus and childhood
      adiposity. METHODS: We studied 282 children aged 7-12 years who were enrolled in
      the Exploring Perinatal Outcomes in Children Study. A genetic risk score for BMI
      was calculated as the count of 91 established BMI-raising risk alleles.
      Multivariable linear and logistic regression models were used to estimate
      associations between the offspring genetic risk score and exposure to gestational
      diabetes and childhood adiposity (BMI and waist circumference), adjusting for
      clinical and demographic covariates. The contribution of offspring genetic risk
      to associations between maternal gestational diabetes and childhood outcomes was
      estimated by comparing the regression coefficients for the gestational diabetes
      variable in models with and without the genetic risk score. RESULTS: The
      offspring BMI genetic risk score was associated with childhood BMI (P = 0.006)
      and waist circumference (P = 0.02), and marginally with gestational diabetes (P =
      0.05). Offspring BMI genetic risk did not contribute significantly to
      associations between gestational diabetes and childhood BMI [7.7% (95% CI -3.3,
      18.8)] or waist circumference [5.8% (95% CI -3.1, 14.8); P = 0.2 for both].
      CONCLUSIONS: Offspring obesity genetic risk does not explain a significant
      proportion of the association between gestational diabetes exposure and childhood
      adiposity. The association between gestational diabetes and childhood adiposity
      is probably explained through alternative pathways, including direct intrauterine
      effects or a shared postnatal environment.

PMID- 29048748
TI  - Accuracy of fetal sex determination in the first trimester of pregnancy using 3D
      virtual reality ultrasound.
AB  - PURPOSE: Early detection of fetal sex is becoming more popular. The aim of this
      study was to evaluate the accuracy of fetal sex determination in the first
      trimester, using 3D virtual reality. METHODS: Three-dimensional (3D) US volumes
      were obtained in 112 pregnancies between 9 and 13 weeks of gestational age. They
      were offline projected as a hologram in the BARCO I-Space and subsequently the
      genital tubercle angle was measured. Separately, the 3D US aspect of the
      genitalia was examined for having a male or female appearance. RESULTS: Although
      a significant difference in genital tubercle angles was found between male and
      female fetuses, it did not result in a reliable prediction of fetal gender.
      Correct sex prediction based on first trimester genital appearance was at best
      56%. CONCLUSION: Our results indicate that accurate determination of the fetal
      sex in the first trimester of pregnancy is not possible, even using an advanced
      3D US technique.

PMID- 29048744
TI  - Comorbidity of Alcohol Use Disorder and Chronic Pain: Genetic Influences on Brain
      Reward and Stress Systems.
AB  - Alcohol use disorder (AUD) is highly comorbid with chronic pain (CP). Evidence
      has suggested that neuroadaptive processes characterized by reward deficit and
      stress surfeit are involved in the development of AUD and pain chronification.
      Neurological data suggest that shared genetic architecture associated with the
      reward and stress systems may contribute to the comorbidity of AUD and CP. This
      monograph first delineates the prevailing theories of the development of AUD and
      pain chronification focusing on the reward and stress systems. It then provides a
      brief summary of relevant neurological findings followed by an evaluation of
      evidence documented by molecular genetic studies. Candidate gene association
      studies have provided some initial support for the genetic overlap between AUD
      and CP; however, these results must be interpreted with caution until studies
      with sufficient statistical power are conducted and replications obtained.
      Genomewide association studies have suggested a number of genes (e.g., TBX19,
      HTR7, and ADRA1A) that are either directly or indirectly related to the reward
      and stress systems in the AUD and CP literature. Evidence reviewed in this
      monograph suggests that shared genetic liability underlying the comorbidity
      between AUD and CP, if present, is likely to be complex. As the advancement in
      molecular genetic methods continues, future studies may show broader central
      nervous system involvement in AUD-CP comorbidity.

PMID- 29048749
TI  - The inheritance of mitochondrial DNA in interspecific Saccharomyces hybrids and
      their properties in winemaking.
AB  - The inheritance of mitochondrial DNA (mtDNA) in yeast hybrids is heteroplasmic,
      turning into homoplasmic after few cell cycles. Mitotype restoration is reported
      to be biparental and random. This study shows that mitotype restoration follows
      fixed schemata. We created isogenic, interspecific Saccharomyces cerevisiae *
      Saccharomyces uvarum hybrids through direct mating and analysed their mating
      frequency and mitotype. The mating frequency increased for most crosses in
      staggered mating. Mitotyping revealed that breeding lines with the same parental
      strain of S. cerevisiae and different parental strains of S. uvarum give rise to
      the same mitotype. According to our results, we postulate that the inheritance of
      mtDNA is dominated by one parental strain and that the superior mitotype is
      specific to each breeding line. Technological tests showed typical hybrid
      heterosis. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29048750
TI  - Isotopic niche variation from the Holocene to today reveals minimal partitioning
      and individualistic dynamics among four sympatric desert mice.
AB  - Species interact with each other and their environment over a range of temporal
      scales, yet our understanding of resource partitioning and the mechanisms of
      species coexistence is largely restricted to modern time-scales of years to
      decades. Furthermore, the relative magnitudes of inter- vs. intraspecific
      variation in resource use are rarely considered, despite the potential for the
      latter to influence a species' ability to cope with changing environmental
      conditions. Modern desert rodent communities are thought to be strongly
      structured by competitive interactions, with niche partitioning of food resources
      hypothesized to explain the coexistence of multiple sympatric granivores. Yet the
      stability of niche dynamics over extended temporal scales within desert rodent
      communities is unknown. I examined the isotopic niche dynamics of four common
      sympatric desert mice (three granivores: Chaetodipus formosus, Perognathus
      longimembris and Reithrodontomys megalotis, and one omnivore: Peromyscus
      maniculatus) in the Smoke Creek Desert of northwestern Nevada using 13 C and 15 N
      isotopes obtained from "Modern" (2008-2013 CE), "Historical" (1989-2005 CE) and
      Holocene fossil specimens spanning the last c. 7,500 years. I found significant
      variation in niche position, niche breadth and interspecific niche overlap of
      these species through time. The niche breadth dynamics of the cricetids (P.
      maniculatus and R. megalotis) were positively correlated with one another, while
      the niche breadth dynamics of the heteromyid C. formosus were negatively
      correlated with those of all other species. Body size, dietary functional group,
      palaeoenvironmental trends and time-averaging provided little explanatory power.
      Importantly, Modern and Historical patterns of resource use and partitioning
      differed from Holocene baselines in terms of decreased niche overlap and in the
      absolute and relative position of each species' niche in at least one isotopic
      axis. These observations suggest that each species' resource use changed
      individualistically over the Holocene, hence niche dynamics are poorly explained
      by the hypothesis of temporally stable species interactions at millennial time
      scales. Furthermore, changes to the resource base over the last century (likely
      due to the spread of invasive cheatgrass) may be increasing resource partitioning
      in the Modern, pushing species past their baseline ranges of resource use
      variation.

PMID- 29048751
TI  - Severity strata for five patient-reported outcomes in adults with atopic
      dermatitis.
AB  - BACKGROUND: Several patient-reported outcomes have been used to assess the burden
      of atopic dermatitis (AD). Some are disease specific, such as the Patient
      Oriented Eczema Measure (POEM), while others pertain to itch, for example the
      numerical rating scale (NRS)-itch, ItchyQoL and 5-D itch, or dermatological
      disease in general, for example the Dermatology Life Quality Index (DLQI).
      Development of severity strata is essential for proper interpretability of these
      assessments. OBJECTIVES: To confirm previously developed strata for POEM, DLQI
      and raw ItchyQoL, and develop strata for the NRS-itch, mean ItchyQoL and 5-D itch
      scale for use in adults with AD. METHODS: Self-administered questionnaires were
      completed by 210 adults with AD in a dermatology practice setting. Strata were
      selected using an anchoring approach based on patient-reported disease severity.
      RESULTS: We confirmed the existing strata for POEM (mild 0-7, moderate 8-16,
      severe 17-28; kappa = 0.440), DLQI (mild 0-5, moderate 6-10, severe 11-30; kappa
      = 0.398) and NRS-itch (mild 0-3, moderate 4-6, severe 7-10; kappa = 0.499).
      However, the preferred band for raw ItchyQoL was mild 22-58, moderate 59-74 and
      severe 75-110 (kappa = 0.379) and for mean ItchyQoL, mild 1-2.9, moderate 3.0
      3.9, severe 4.0-5.0 (kappa = 0.374). The preferred band for 5-D itch scale was
      mild 0-11, moderate 12-17 and severe 18-25 (kappa = 0.331). CONCLUSIONS: Existing
      strata for POEM and DLQI performed well in adult AD. Previously reported strata
      for visual analogue scale-itch performed best for NRS-itch. We identified banding
      for the raw ItchyQoL for our AD population that varies slightly from the banding
      published for a more heterogeneous population. Finally, we proposed strata for
      mean ItchyQoL and 5-D itch scale in adult AD.

PMID- 29048753
TI  - Medication errors at hospital admission and discharge in Type 1 and 2 diabetes.
AB  - AIMS: To assess the prevalence and characteristics of medication errors at
      hospital admission and discharge in people with Type 1 and Type 2 diabetes, and
      identify potential risk factors for these errors. METHODS: This prospective
      observational study included all people with Type 1 (n = 163) and Type 2 diabetes
      (n = 508) admitted to the Diabetology-Department of the University Hospital of
      Montpellier, France, between 2013 and 2015. Pharmacists conducted medication
      reconciliation within 24 h of admission and at hospital discharge. Medication
      history collected from different sources (patient/family interviews,
      prescriptions/medical records, contact with community pharmacies/general
      practitioners/nurses) was compared with admission and discharge prescriptions to
      detect unintentional discrepancies in medication indicating involuntary
      medication changes. Medication errors were defined as unintentional medication
      discrepancies corrected by physicians. Risk factors for medication errors and
      serious errors (i.e. errors that may cause harm) were assessed using logistic
      regression. RESULTS: A total of 322 medication errors were identified and were
      mainly omissions. Prevalence of medication errors in Type 1 and Type 2 diabetes
      was 21.5% and 22.2% respectively at admission, and 9.0% and 12.2% at discharge.
      After adjusting for age and number of treatments, people with Type 1 diabetes had
      nearly a twofold higher odds of having medication errors (odds ratio (OR) 1.72,
      95% confidence interval (CI) 1.02-2.94) and serious errors (OR 2.17, 95% CI 1.02
      4.76) at admission compared with those with Type 2 diabetes. CONCLUSIONS:
      Medication reconciliation identified medication errors in one third of
      individuals. Clinical pharmacists should focus on poly-medicated individuals, but
      also on other high-risk people, for example, those with Type 1 diabetes.

PMID- 29048754
TI  - Randomized controlled trial of the effect of endometrial injury on implantation
      and clinical pregnancy rates during the first ICSI cycle.
AB  - OBJECTIVE: To assess whether endometrial injury in the cycle preceding controlled
      ovarian hyperstimulation during intracytoplasmic sperm injection (ICSI) improves
      the implantation and pregnancy rates. METHODS: Between January 1, 2016, and March
      31, 2017, a randomized controlled trial was conducted at a center in Egypt among
      300 women who met inclusion criteria (first ICSI cycle, aged <40 years, day-3
      follicle-stimulating hormone <10 IU/L, normal serum prolactin, no uterine cavity
      abnormality). The women were randomly allocated using a web-based system to
      undergo endometrial scratch in the cycle preceding controlled ovarian
      hyperstimulation (n=150) or to a control group (n=150). Only data analysts were
      masked to group assignment. The primary outcomes were the implantation and
      clinical pregnancy rates at 14 days and 4 weeks after embryo transfer,
      respectively. Analyses were by intention to treat. RESULTS: The implantation rate
      was significantly higher in the endometrial scratch group (41.3% [90/218]) than
      in the control group (30.0% [63/210]; P<0.001). The clinical pregnancy rate was
      also significantly higher in the endometrial scratch group (44.2% [61/138]) than
      in the control group (30.4% [41/135]; P<0.001). CONCLUSION: Endometrial injury in
      the cycle preceding the stimulation cycle improved implantation and pregnancy
      rates during ICSI. CLINICALTRIALS.GOV: NCT02660125.

PMID- 29048756
TI  - Metal-Free, Site-Selective Peptide Modification by Conversion of "Customizable"
      Units into beta-Substituted Dehydroamino Acids.
AB  - Our site-selective modification of serine or threonine units in peptides allows
      the generation of beta-substituted dehydroamino acids, which increase peptide
      resistance to hydrolysis and may improve their biological properties. Both the
      terminal and internal positions can be modified, and different customizable units
      can be activated separately. Remarkably, high Z selectivity is achieved, even at
      internal positions. The conversion involves a one-pot oxidative radical
      scission/phosphorylation process by using the low-toxicity
      (diacetoxyiodo)benzene/iodine system as the scission reagent. The resulting alpha
      amino phosphonates undergo a Horner-Wadsworth-Emmons reaction to produce the
      dehydroamino acid derivatives (in a Z/E ratio of usually >98:2) under mild and
      metal-free conditions.

PMID- 29048752
TI  - The 'how' and 'where' of plant microRNAs.
AB  - Contents 1002 I. 1002 II. 1007 III. 1010 IV. 1013 1013 References 1013 SUMMARY:
      MicroRNAs (miRNAs) are small non-coding RNAs, of typically 20-24 nt, that
      regulate gene expression post-transcriptionally through sequence complementarity.
      Since the identification of the first miRNA, lin-4, in the nematode
      Caenorhabditis elegans in 1993, thousands of miRNAs have been discovered in
      animals and plants, and their regulatory roles in numerous biological processes
      have been uncovered. In plants, research efforts have established the major
      molecular framework of miRNA biogenesis and modes of action, and are beginning to
      elucidate the mechanisms of miRNA degradation. Studies have implicated restricted
      and surprising subcellular locations in which miRNA biogenesis or activity takes
      place. In this article, we summarize the current knowledge on how plant miRNAs
      are made and degraded, and how they repress target gene expression. We discuss
      not only the players involved in these processes, but also the subcellular sites
      in which these processes are known or implicated to take place. We hope to raise
      awareness that the cell biology of miRNAs holds the key to a full understanding
      of these enigmatic molecules.

PMID- 29048755
TI  - Nifedipine Prevents Apoptosis of Alcohol-Exposed First-Trimester Trophoblast
      Cells.
AB  - BACKGROUND: Maternal alcohol abuse leading to fetal alcohol spectrum disorder
      (FASD) includes fetal growth restriction (FGR). Ethanol (EtOH) induces apoptosis
      of human placental trophoblast cells, possibly disrupting placentation and
      contributing to FGR in FASD. EtOH facilitates apoptosis in several embryonic
      tissues, including human trophoblasts, by raising intracellular Ca2+ . We
      previously found that acute EtOH exposure increases trophoblast apoptosis due to
      signaling from both intracellular and extracellular Ca2+ . Therefore, nifedipine,
      a Ca2+ channel blocker that is commonly administered to treat preeclampsia and
      preterm labor, was evaluated for cytoprotective properties in trophoblast cells
      exposed to alcohol. METHODS: Human first-trimester chorionic villous explants and
      the human trophoblast cell line HTR-8/SVneo (HTR) were pretreated with 12.5 to 50
      nM of the Ca2+ channel blocker nifedipine for 1 hour before exposure to 50 mM
      EtOH for an additional hour. Intracellular Ca2+ concentrations were monitored in
      real time by epifluorescence microscopy, using fluo-4-AM. Apoptosis was assessed
      by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL),
      accumulation of cytoplasmic cytochrome c, and cleavage rates of caspase 3 and
      caspase 9. RESULTS: The increase in intracellular Ca2+ upon exposure to EtOH in
      both villous explants and HTR cells was completely blocked (p < 0.05) when
      pretreated with nifedipine, accompanied by inhibition of EtOH-induced release of
      cytochrome c, caspase activities, and TUNEL. CONCLUSIONS: This study indicates
      that nifedipine can interrupt the apoptotic pathway downstream of EtOH exposure
      and could provide a novel strategy for future interventions in women with fetuses
      at risk for FASD.

PMID- 29048757
TI  - Determinants of orchid species diversity in world islands.

PMID- 29048758
TI  - Phenological synchrony between a butterfly and its host plants: Experimental test
      of effects of spring temperature.
AB  - Climate-driven changes in the relative phenologies of interacting species may
      potentially alter the outcome of species interactions. Phenotypic plasticity is
      expected to be important for short-term response to new climate conditions, and
      differences between species in plasticity are likely to influence their temporal
      overlap and interaction patterns. As reaction norms of interacting species may be
      locally adapted, any such climate-induced change in interaction patterns may vary
      among localities. However, consequences of spatial variation in plastic responses
      for species interactions are understudied. We experimentally explored how
      temperature affected synchrony between spring emergence of a butterfly,
      Anthocharis cardamines, and onset of flowering of five of its host plant species
      across a latitudinal gradient. We also studied potential effects on synchrony if
      climate-driven northward expansions would be faster in the butterflies than in
      host plants. Lastly, to assess how changes in synchrony influence host use we
      carried out an experiment to examine the importance of the developmental stage of
      plant reproductive structures for butterfly oviposition preference. In southern
      locations, the butterflies were well-synchronized with the majority of their
      local host plant species across temperatures, suggesting that thermal plasticity
      in butterfly development matches oviposition to host plant development and that
      thermal reaction norms of insects and plants result in similar advancement of
      spring phenology in response to warming. In the most northern region, however,
      relative phenology between the butterfly and two of its host plant species
      changed with increased temperature. We also show that the developmental stage of
      plants was important for egg-laying, and conclude that temperature-induced
      changes in synchrony in the northernmost region are likely to lead to shifts in
      host use in A. cardamines if spring temperatures become warmer. Northern
      expansion of butterfly populations might possibly have a positive effect on
      keeping up with host plant phenology with more northern host plant populations.
      Considering that the majority of insect herbivores exploit multiple plant species
      differing in their phenological response to spring temperatures, temperature
      induced changes in synchrony might lead to shifts in host use and changes in
      species interactions in many temperate communities.

PMID- 29048761
TI  - Corrigendum.

PMID- 29048760
TI  - CD10 and the nail.

PMID- 29048762
TI  - Clinical factors associated with the symptoms of constipation in patients with
      diabetes mellitus: A multicenter study.
AB  - BACKGROUND AND AIM: Changes in treatment protocols for patients with diabetes
      mellitus (DM) may influence the functions of the digestive tract. This study
      examined possible clinical factors associated with the symptoms of constipation
      in patients with DM. METHODS: This was a multicenter study. Participants were
      consecutive Japanese patients undergoing treatment for type 1 or type 2 DM.
      Constipation was evaluated using the gastrointestinal symptom rating scale.
      Diabetic neuropathy was evaluated by the presence or absence of peripheral
      neuropathy of the lower limbs. RESULTS: Of 419 participants, 258 were men and 161
      women (ratio: 1.6:1), with a mean age of 63.6 +/- 12.5 years. In multivariate
      analysis, symptoms of constipation were significantly associated with age (odds
      ratio [OR] = 1.02, 95% confidence interval [CI]: 1.01-1.04, P = 0.032), lower
      mental component summary (OR = 3.31, 95% CI: 1.69-6.48, P < 0.001), diabetic
      retinopathy (OR = 1.99, 95% CI: 1.14-3.45, P = 0.015), and diabetic neuropathy
      (OR = 1.86, 95% CI: 1.10-3.16, P = 0.021). In patients with peripheral neuropathy
      of the lower limbs, regardless of the presence of other complications (diabetic
      nephropathy and diabetic retinopathy), the prevalence of symptoms of constipation
      was twice that of patients without peripheral neuropathy (40.0-49.1% vs 22.0%).
      Diabetic drugs were not associated with symptoms of constipation. CONCLUSIONS:
      Diabetic neuropathy, defined as peripheral neuropathy of the lower limbs, was
      significantly associated with symptoms of constipation. Peripheral neuropathy of
      the lower limbs is not a direct risk factor for constipation but may be a useful
      criterion when assessing whether constipation is associated with DM.

PMID- 29048763
TI  - Cubane Cross-Coupling and Cubane-Porphyrin Arrays.
AB  - Herein, an improved methodology for aryl-cubane cross-coupling is reported. The
      peculiarities of the cubane core and its behavior during cross-coupling
      conditions were analyzed, while the versatility of this adapted Baran cross
      coupling methodology was demonstrated by the synthesis of various aryl-cubane
      systems, including coupling products of cubanes and porphyrins. Furthermore, arm
      extension of alkynyl-cubanes by Sonogashira reactions is demonstrated, showcasing
      the first proof of the stability of the cubane core in the presence of palladium
      catalysts.

PMID- 29048764
TI  - Supramolecular Storage and Controlled Photorelease of an Oxidizing Agent using a
      Bambusuril Macrocycle.
AB  - The oxidizing ability of peroxodisulfate upon complexation inside the Bambusuril
      macrocycle cavity is inhibited. This dianionic agent can be released on demand
      from its stable 1:1 complex in water (log Ka =6.9 m-1 ) by addition of a more
      strongly bound anion, such as iodide (log Ka =7.1 m-1 ), which can also be
      delivered in situ upon irradiation from a 4-hydroxyphenacyl iodide derivative
      with spatial and temporal precision. The oxidizing properties of peroxodisulfate
      ions liberated from the complex recover and can take part in subsequent chemical
      transformations.

PMID- 29048766
TI  - The use of emotional intelligence capabilities in clinical reasoning and decision
      making: A qualitative, exploratory study.
AB  - AIMS AND OBJECTIVES: To explore clinical nurses' experiences of using emotional
      intelligence capabilities during clinical reasoning and decision-making.
      BACKGROUND: There has been little research exploring whether, or how, nurses
      employ emotional intelligence (EI) in clinical reasoning and decision-making.
      DESIGN: Qualitative phase of a larger mixed-methods study. METHODS:
      Semistructured qualitative interviews with a purposive sample of registered
      nurses (n = 12) following EI training and coaching. Constructivist thematic
      analysis was employed to analyse the narrative transcripts. RESULTS: Three themes
      emerged: the sensibility to engage EI capabilities in clinical contexts,
      motivation to actively engage with emotions in clinical decision-making and
      incorporating emotional and technical perspectives in decision-making.
      CONCLUSION: Continuing to separate cognition and emotion in research, theorising
      and scholarship on clinical reasoning is counterproductive. RELEVANCE TO CLINICAL
      PRACTICE: Understanding more about nurses' use of EI has the potential to improve
      the calibre of decisions, and the safety and quality of care delivered.

PMID- 29048765
TI  - Ageratum conyzoides L. inhibits 5-alpha-reductase gene expression in human
      prostate cells and reduces symptoms of benign prostatic hypertrophy in otherwise
      healthy men in a double blind randomized placebo controlled clinical study.
AB  - A double-blind, randomized, placebo-controlled clinical trial assessed the
      efficacy and safety of Ageratum conyzoides in treating benign prostatic
      hypertrophy (BPH). In this study, 109 men with medically diagnosed BPH, aged 41
      76 years, were administered the investigational product, A. conyzoides extract at
      a dose of 250 mg/d or placebo, q.d. for 12 weeks. The primary outcome measures
      were the International Prostate Symptom Score (IPSS), daily urinary frequency and
      safety evaluations. The secondary outcome measures were testosterone,
      dihydrotestosterone, oestradiol, sex hormone binding globulin (SHBG),
      Dehydroepiandrosterone sulfate (DHEA-S) and cortisol levels, and prostate
      specific antigen (PSA), lipids, blood glucose, the Aging Male's Symptom (AMS)
      Score and sexual function assessed by Derogatis Interview for Sexual Functioning
      Self Report (DISF-SR). The effect of A. conyzoides L extract on gene expression
      of 5-alpha-reductase in human prostate cells was also investigated to elucidate a
      potential mechanism of action. The clinical study, showed a significant reduction
      in total IPSS score (p < 0.01) and day- and night-time urinary frequency (P <
      0.01) over time after treatment with A. conyzoides. Steroid hormones, SHBG, PSA
      levels, lipids, and blood glucose remained within healthy reference range in both
      groups. There were no changes in AMS or DISF-SR in either group. Gene arrays
      demonstrated that A. conyzoides extract was effective in reducing the expression
      of mRNA coding for 5-alpha-reductase types 2 and 1 in human prostate epithelial
      cells. The overall results indicate that A. conyzoides may be an effective
      treatment for reducing symptoms of BPH in healthy men, in part, through
      inhibition of 5-alpha-reductase enzyme activity. (c) 2017 BioFactors, 43(6):789
      800, 2017.

PMID- 29048767
TI  - Risk assessment and subsequent nursing interventions in a forensic mental health
      inpatient setting: Associations and impact on aggressive behaviour.
AB  - AIM AND OBJECTIVES: To examine associations between risk of aggression and
      nursing interventions designed to prevent aggression. BACKGROUND: There is scarce
      empirical research exploring the nature and effectiveness of interventions
      designed to prevent inpatient aggression. Some strategies may be effective when
      patients are escalating, whereas others may be effective when aggression is
      imminent. Research examining level of risk for aggression and selection and
      effectiveness of interventions and impact on aggression is necessary. DESIGN:
      Archival case file. METHODS: Data from clinical files of 30 male and 30 female
      patients across three forensic acute units for the first 60 days of
      hospitalisation were collected. Risk for imminent aggression as measured by the
      Dynamic Appraisal of Situational Aggression, documented nursing interventions
      following each assessment, and acts of aggression within the 24-hours following
      assessment were collected. Generalised estimating equations were used to
      investigate whether intervention strategies were associated with reduction in
      aggression. RESULTS: When a Dynamic Appraisal of Situational Aggression
      assessment was completed, nurses intervened more frequently compared to days when
      no Dynamic Appraisal of Situational Aggression assessment was completed. Higher
      Dynamic Appraisal of Situational Aggression assessments were associated with a
      greater number of interventions. The percentage of interventions selected for
      males differed from females; males received more pro re nata medication and
      observation, and females received more limit setting, one-to-one nursing and
      reassurance. Pro re nata medication was the most commonly documented intervention
      (35.9%) in this study. Pro re nata medication, limit setting and reassurance were
      associated with an increased likelihood of aggression in some risk bands.
      CONCLUSIONS: Structured risk assessment prompts intervention, and higher risk
      ratings result in more interventions. Patient gender influences the type of
      interventions. Some interventions are associated with increased aggression,
      although this depends upon gender and risk level. RELEVANCE TO CLINICAL PRACTICE:
      When structured risk assessments are used, there is greater likelihood of
      intervention. Intervention should occur early using least restrictive
      interventions.

PMID- 29048768
TI  - Family-centred care for families living with cystic fibrosis in a rural setting:
      A qualitative study.
AB  - AIMS AND OBJECTIVES: To explore experiences of family-centred care among parents
      of children with cystic fibrosis living far from tertiary treatment centres and
      to understand what such distances mean to their care. BACKGROUND: Australia is a
      large continent. However, many families with a child with cystic fibrosis live in
      regional areas, often thousands of kilometres away from the primary treatment
      centres located in Australia's coastal capital cities. DESIGN: A qualitative,
      phenomenological design using a Van Manen () approach. METHODS: Individual, semi
      structured interviews were conducted with parents (n = 7) of a child with cystic
      fibrosis who lived in regional Australia. Thematic content data analysis was
      used. RESULTS: The essence of the participants' experience was their seeking
      certainty and continuity in the changeable realm of cystic fibrosis while
      negotiating a collaborative approach to their child's care. Five core themes and
      two subthemes were identified: "Daily care: a family affair," including the
      subtheme "Accessing expert care"; "Family-centred care: seeking inclusion";
      "Control versus collaboration: seeking mutual trust," with the subtheme "The team
      who grows with you"; "Future projections"; and "The CF circle." CONCLUSION: Some
      concerns are not unlike those of their city counterparts, but can be intensified
      by their sense of distance and isolation. RELEVANCE TO CLINICAL PRACTICE: Insight
      into this unique milieu from the parents' perspective is requisite so that care
      is appropriate to such a challenging environment and incorporates the whole
      family.

PMID- 29048769
TI  - In vivo implantation of a tissue engineered stem cell seeded hemi-laryngeal
      replacement maintains airway, phonation, and swallowing in pigs.
AB  - Laryngeal functional impairment relating to swallowing, vocalisation, and
      respiration can be life changing and devastating for patients. A tissue
      engineering approach to regenerating vocal folds would represent a significant
      advantage over current clinical practice. Porcine hemi-larynx were de
      cellularised under negative pressure. The resultant acellular scaffold was seeded
      with human bone marrow derived mesenchymal stem cells and primary human
      epithelial cells. Seeded scaffolds were implanted orthotopically into a defect
      created in the thyroid cartilage in 8 pigs and monitored in vivo for 2 months. In
      vivo assessments consisted of mucosal brushing and bronchoscopy at 1, 2, 4, and 8
      weeks post implantation followed by histological evaluation post termination. The
      implanted graft had no adverse effect on respiratory function in 6 of the 8 pigs;
      none of the pigs had problems with swallowing or vocalisation. Six out of the 8
      animals survived to the planned termination date; 2 animals were terminated due
      to mild stenosis and deep tissue abscess formation, respectively. Human
      epithelial cells from mucosal brushings could only be identified at Weeks 1 and
      4. The explanted tissue showed complete epithelialisation of the mucosal surface
      and the development of rudimentary vocal folds. However, there was no evidence of
      cartilage remodelling at the relatively early censor point. Single stage partial
      laryngeal replacement is a safe surgical procedure. Replacement with a tissue
      engineered laryngeal graft as a single procedure is surgically feasible and
      results in appropriate mucosal coverage and rudimentary vocal fold development.

PMID- 29048770
TI  - Isoquinoline-1-Carboxylate as a Traceless Leaving Group for Chelation-Assisted
      Glycosylation under Mild and Neutral Reaction Conditions.
AB  - Glycosyl isoquinoline-1-carboxylate was developed as a novel benchtop stable and
      readily available glycosyl donor. The glycosylation reaction was promoted by the
      inexpensive Cu(OTf)2 salt under mild reaction conditions. The copper isoquinoline
      1-carboxylate salt was precipitated from the solution and thus rendered a
      traceless leaving group. Surprisingly, the proton from the acceptor was absorbed
      by the precipitated metal complex and the reaction mixture remained at neutral
      pH. The copper-promoted glycosylation was also proven to be completely orthogonal
      to the gold-promoted glycosylation, and an iterative synthesis of
      oligosaccharides from benchtop stable anomeric ester building blocks becomes
      possible under mild reaction conditions.

PMID- 29048771
TI  - Catecholaminergic polymorphic ventricular tachycardia, an update.
AB  - Catecholaminergic polymorphic ventricular tachycardia is a rare devastating
      lethal inherited disorder or sporadic cardiac ion channelopathy characterized by
      unexplained syncopal episodes, and/or sudden cardiac death (SCD), aborted SCD
      (ASCD), or sudden cardiac arrest (SCA) observed in children, adolescents, and
      young adults without structural heart disease, consequence of adrenergically
      mediated arrhythmias: exercise-induced, by acute emotional stress, atrial pacing,
      or beta-stimulant infusion, even when the electrocardiogram is normal. The entity
      is difficult to diagnose in the emergency department, given the range of
      presentations; thus, a familiarity with and high index of suspicion for this
      pathology are crucial. Furthermore, recognition of the characteristic findings
      and knowledge of the management of symptomatic patients are necessary, given the
      risk of arrhythmia recurrence and SCA. In this review, we will discuss the
      concept, epidemiology, genetic background, genetic subtypes, clinical
      presentation, electrocardiographic features, diagnosis criteria, differential
      diagnosis, and management.

PMID- 29048772
TI  - What the neighbors say.

PMID- 29048773
TI  - Use of a Rho kinase inhibitor to increase human tonsil keratinocyte longevity for
      three-dimensional, tissue engineered tonsil epithelium equivalents.
AB  - The generation of tissue-engineered epithelial models is often hampered by the
      limited proliferative capacity of primary epithelial cells. This study aimed to
      isolate normal tonsillar keratinocytes (NTK) from human tonsils, increase the
      lifespan of these cells using the Rho kinase inhibitor Y-27632 and to develop
      tissue-engineered equivalents of healthy and infected tonsil epithelium. The
      proliferation rate of isolated NTK and expression of c-MYC and p16INK4A were
      measured in the absence or presence of the inhibitor. Y-27632-treated NTK were
      used to generate tissue-engineered tonsil epithelium equivalents using de
      epidermised dermis that were then incubated with Streptococcus pyogenes to model
      bacterial tonsillitis, and the expression of pro-inflammatory cytokines was
      measured by cytokine array and ELISA. NTK cultured in the absence of Y-27632
      rapidly senesced whereas cells cultured in the presence of this inhibitor
      proliferated for over 30 population doublings without changing their phenotype. Y
      27632-treated NTK produced a multi-layered differentiated epithelium that
      histologically resembled normal tonsillar surface epithelium and responded to S.
      pyogenes infection by increased expression of pro-inflammatory cytokines
      including CXCL5 and IL-6. NTK can be isolated and successfully cultured in vitro
      with Y-27632 leading to a markedly prolonged lifespan without any deleterious
      consequences to cell morphology. This functional tissue-engineered equivalent of
      tonsil epithelium will provide a valuable tool for studying tonsil biology and
      host-pathogen interactions in a more physiologically relevant manner.

PMID- 29048775
TI  - Nursing documentation in inpatient psychiatry: The relevance of nurse-patient
      interactions in progress notes-A focus group study with mental health staff.
AB  - AIMS AND OBJECTIVES: To gain insight into mental health staff's perception of
      writing progress notes in an acute and subacute psychiatric ward context.
      BACKGROUND: The nursing process structures nursing documentation. Progress notes
      are intended to be an evaluation of a patient's nursing diagnoses, interventions
      and outcomes. Within this template, a patient's status and the care provided are
      to be recorded. The therapeutic nurse-patient relationship is recognised as a key
      component of psychiatric care today. At the same time, the biomedical model
      remains strong. Research literature exploring nursing staff's experiences with
      writing progress notes in psychiatric contexts, and especially the space given to
      staff-patient relations, is sparse. DESIGN: Qualitative design. METHODS: Focus
      group interviews with mental health staff working in one acute and one subacute
      psychiatric ward were conducted. Systematic text condensation, a method for
      transverse thematic analysis, was used. RESULTS: Two main categories emerged from
      the analysis: the position of the professional as an expert and distant observer
      in the progress notes, and the weak position of professional-patient interactions
      in progress notes. CONCLUSIONS: The participants did not perceive that the
      current recording model, which is based on the nursing process, supported a focus
      on patients' resources or reporting professional-patient interactions. This model
      appeared to put ward staff in an expert position in relation to patients, which
      made it challenging to involve patients in the recording process. Essential
      aspects of nursing care related to recovery and person-centred care were not
      prioritised for documentation. RELEVANCE TO CLINICAL PRACTICE: This study
      contributes to the critical examination of the documentation praxis, as well as
      to the critical examination of the documentation tool as to what is considered
      important to document.

PMID- 29048776
TI  - Jackie Robinson, the Anatomical Record, and the Gift of Building Bridges.

PMID- 29048777
TI  - Nurses' perspectives on how an e-message system supports cross-sectoral
      communication in relation to medication administration: A qualitative study.
AB  - AIMS AND OBJECTIVES: To describe nurses' perspectives on how an e-message system
      supports communication between hospital and home care nurses in relation to
      medication administration. BACKGROUND: Medication administration is a complex
      process involving a high risk of error. Unclear communication and lack of updated
      information about medication have been identified as the leading cause of
      medication errors during care transitions. E-message systems are progressively
      being used to improve information exchange across sectors, yet little is known
      about their usage for exchange of medication information between nurses. DESIGN:
      A qualitative design using content analysis. METHODS: Focus group interviews were
      conducted with nurses from eight hospital wards and six municipalities (n = 79).
      Participant observations were conducted in three hospital wards and in three
      municipalities (165 hr). RESULTS: The e-message system did not provide the
      information needed by the home care nurses to ensure safe medication
      administration after discharge due to (1) limitations of the system, (2) hospital
      nurses' lack of knowledge about home care nurses' information needs and (3)
      hospital nurses' lack of access to medication information. Due the home care
      nurses' perception of responsibility, they bypassed the e-message system to get
      the information. CONCLUSIONS: The home care nurses perceived themselves as the
      last link in the safety chain. As such, access to adequate information was
      essential for the nurses to ensure safe medication administration; however, the e
      message system did not support exchange of the information needed. RELEVANCE TO
      CLINICAL PRACTICE: E-message systems must meet home care nurses' need for
      information to ensure that safe medication administration does not depend on the
      knowledge of the individual nurse. Moreover, other system factors that influence
      interprofessional collaboration and nurses' cross-sectoral communication must be
      addressed.

PMID- 29048778
TI  - New developments in cytometric phenotyping.

PMID- 29048779
TI  - Cytometry Part A-ISAC Marylou Ingram Scholars and SRL Emerging Leaders Mentorship
      Program: The next step.

PMID- 29048781
TI  - [Preparation of large-pore silica microspheres using templating method and their
      applications to protein separation with high performance liquid chromatography].
AB  - Large-pore silica microspheres were synthesized by utilizing weak cation exchange
      polymer beads as templates, N-trimethoxysilylpropyl-N,N,N-trimethylammonium
      chloride (TMSPTMA) as a structure-directing agent, tetraethoxysilane (TEOS) as a
      silica precursor, and triethanolamine as a weak base catalyst. The hydrolysis and
      condensation of the silica precursors occurred inside the templating polymer
      beads yielded polymer/silica composite microspheres. After the organic polymer
      templates were removed in the calcination step, large-pore silica microspheres
      were produced. The effects of different reaction conditions on the morphology,
      structure and dispersibility of the formed silica microspheres were investigated.
      It has been shown that when the volume ratio of TMSPTMA, TEOS and triethanolamine
      was 1:2:2, silica microspheres with pore size range of 50-150 nm and particle
      size around 2 MUm were obtained. The as-prepared silica microspheres were then
      bonded with chlorodimethyloctadecylsilane (C18), packed into a 50 mm*4.6 mm
      column, and evaluated for the separations of some common standard proteins and
      soybean isolation proteins. The results showed that the large-pore silica spheres
      from this work have potentials for protein separation in HPLC.

PMID- 29048782
TI  - [Preparation and chiral recognition of heterosubstituted amylose derivatives
      based chiral stationary phases].
AB  - Two novel amylose derivatives, namely amylose 2-benzoate-3-(4
      methylphenylcarbamate)-6-(3,5-dichlorophenylcarbamate) and amylose 2-benzoate-3
      (3,5-dichlorophenylcarbamate)-6-(4-methylphenylcarbamate), were prepared
      utilizing a serial regioselective process. After coated onto aminopropyl silica
      gel, they were utilized as chiral stationary phases (CSPs) for high performance
      liquid chromatography. Investigations indicated that the CSPs exhibited
      characteristic chiral recognition and their chiral recognition abilities were
      much higher than those of amylose tris(3,5-dichlorophenylcarbamate) (ADCPC), a
      homosubstituted derivative. The nature and position of the substituents at 3-,
      and 6-positions of a glucose unit had great influence on the chiral resolution
      abilities of the amylose derivatives. Some chiral compounds which were not
      effectively resolved on the commercial column Chiralpak AD were effectively
      separated on the new CSPs. Moreover, with all the eight tested racemates
      resolved, amylose 2-benzoate-3-(4-methylphenylcarbamate)-6-(3,5
      dichlorophenylcarbamate) exhibited relatively high chiral recognition and might
      be a potential useful CSP.

PMID- 29048780
TI  - Magnesium isoglycyrrhizinate promotes the activated hepatic stellate cells
      apoptosis via endoplasmic reticulum stress and ameliorates fibrogenesis in vitro
      and in vivo.
AB  - Varied pathogenetic elements have been touched upon the liver fibrosis, including
      inflammatory, stress, apoptosis and unfolded proteins aggregation. Magnesium
      Isoglycyrrhizinate (MgIG) has been accepted to be a neuroprotective effect,
      hepatoprotective and anti-inflammatory molecule. In our vitro researches, MgIG
      was considered to activate hepatic stellate cells (HSCs) apoptosis by promoting
      endoplasmic reticulum stress (ERS) detrimental response to a certain extent.
      Consequently, MgIG showed its potential therapeutic capacity in fibrogenesis and
      counteracted the pathogenetic aspects, which were involved in integrating current
      treatments correcting liver fibrosis. In addition, we further verificated the
      behavior and pathogenic mechanisms in the CCl4 -induced liver fibrosis in male
      mice. What surprised us was that with the treatment of MgIG caused the activation
      of ERS and resisted the activated HSCs in the protective effects on liver damage.
      We found MgIG significantly promoted the apoptosis of activated HSCs and
      protected the CCl4 -induced liver fibrosis. Main molecules came down to the
      unfolded protein response signaling pathway. Furthermore, MgIG inhibited the
      levels of the downstream inflammatory cytokines, which were triggered by CCl4 
      induced liver fibrosis. Here, we reported that MgIG improved behavioral
      impairments induced by intraperitoneal injection of CCl4 and decreased the
      expression of proinflammatory factor, which indicated the preserving effects on
      liver fibrosis. (c) 2017 BioFactors, 43(6):836-846, 2017.

PMID- 29048783
TI  - [Investigation on silymarin impact on lipopolysaccharide induced inflammation
      model based on arachidonic acid metabolism pathway].
AB  - The objective of this research is to investigate the suppressive effect of
      silymarin on vitro cell culture model of inflammatory macrophage RAW264.7 induced
      by Kdo2-Lipid A, and explore its mechanism based on cell metabonomics. Ultra-high
      performance liquid chromatography coupled with tandem mass spectrometry (UPLC
      MS/MS) method was used in the cell metabonomic assay to quantitative analysis of
      metabolites related to eicosanoids pathway. Then chemometric approaches such as
      principal component analysis were used to process the metabolic data. Within the
      established method, a total of 59 eicosanoids standards (containing 15 deuterated
      internal standards) were simultaneously separated in a single 5 min run, and the
      analytical method is proved to be rapid, sensitive and accurate. Whereafter, the
      metabolites with VIP> 1 and P value< 0.05 were considered as biomarkers. 12
      OxoLeukotriene B4 (12-OxoLTB4) was eventually identified as metabolic biomarkers
      of silymarin treatment group in this research, and according to the related
      inflammatory pathways, we speculated silymarin has anti-inflammatory activities
      by inhibiting the 5-lipoxygenase (5-LOX) activity and blocking lipid peroxidation
      in 5-LOX metabolic pathways to reduce the formation of peroxides and oxygen free
      radicals. This study provide a novel approach to the mechanism research on the
      silymarin treatment on RAW264.7 cells based on cell metabonomics.

PMID- 29048784
TI  - [Tracking casein phosphopeptides during fermentation by high performance liquid
      chromatography-tandem mass spectrometry].
AB  - Casein phosphopeptides (CPPs) are phosphorylated fragments of casein, which have
      a variety of biological functions such as promotion of mineral absorption,
      antioxidation and prevention of dental caries. This study investigated CPPs in
      milk and yogurt fermented by Lb. bulgaricus (Lactobacillus debrueckii subsp.
      bulgaricus) and S. thermophilus (Streptococcus thermophilus) with high
      performance liquid chromatography-tandem mass spectrometry. The results showed
      that milk contained endogenous CPPs, which were mainly derived from high
      abundance of caseins alphas1-CN and beta-CN, in the role of endogenous protease.
      After milk fermented with Lb. bulgaricus and S. thermophilus, more CPPs and
      phosphorylation sites were released in the action of lactic acid bacteria
      proteases. The CPPs with the character of SpSpSpEE were identified in yogurt. The
      structure of caseins played an important role in CPPs releasing in the process of
      fermentation. In conclusion, fermentation by lactic acid bacteria is helpful to
      release CPPs containing SpSpSpEE, which can promote mineral absorption.

PMID- 29048785
TI  - [Determination of 34 illegally adulterated weight loss compounds in foods by
      ultra high performance liquid chromatography- triple quadrupole mass
      spectrometry].
AB  - An analytical method was developed for the determination of 34 illegally
      adulterated weight loss compounds in foods and dietary supplements by ultra high
      performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC
      MS/MS). A Waters CORTECS T3 column (100 mm*2.1 mm, 2.7 MUm) was used with 0.1%
      (v/v) formic acid aqueous solution-acetonitrile containing 0.1% (v/v) formic acid
      as mobile phases by gradient elution. The compounds were detected by electrospray
      ion source in positive or negative mode with multiple reaction monitoring (MRM)
      mode. The calibration curves showed good linearity in the range of 0.5-10 MUg/L
      for 29 compounds such as sibutramine, and in the range of 2.5-50 MUg/L for five
      compounds such as chlorothiazide. The correlation coefficients (r) of the
      standard calibration curves for the 34 analytes were all greater than 0.99. The
      recoveries of the 29 compounds at spiked levels of 5, 10 and 20 MUg/kg were in
      the range of 49.2%-136.2%, and the RSDs were 0.7%-15.0% (n=6). The recoveries of
      the five compounds at spiked levels of 25, 50 and 100 MUg/kg were in the range of
      51.5%-130.9%, and the RSDs were 0.8%-14.0% (n=6). The limits of detection (LODs)
      and limits of quantification (LOQs) were 5 MUg/kg and 10 MUg/kg for the 29
      compounds, 25 MUg/kg and 50 MUg/kg for the five compounds, respectively. The
      method was successfully applied to the analysis of actual samples, and 12
      compounds were checked out, which combated the illegal adulteration behavior
      effectively.

PMID- 29048786
TI  - [Simultaneous determination of five mycotoxins in various grains and their
      products by liquid chromatography-tandem mass spectrometry with isotope internal
      standard].
AB  - A rapid method was established for the determination of zearalenone (ZON),
      nivalenol (NIV), deoxynivalenol (DON), 3-acetyl-deoxynivalenol (3-ACDON) and 15
      acetyl-deoxynivalenol (15-ACDON) in various grains and their products by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The samples were extracted by
      acetonitrile-water (84:16, v/v), and cleaned-up by multifunctional column without
      any further step. The separation was carried out on an Acquity UPLC(r) BEH C18
      column (100 mm*2.1 mm, 1.7 MUm) with gradient elution using acetonitrile-water as
      mobile phases. The analytes were quantified by isotope internal standard method.
      The correlation coefficients (r2) were all above 0.99. The limits of detection
      (LODs, S/N=3) ranged from 5 MUg/kg to 20 MUg/kg. The recoveries of the five
      mycotoxins spiked in blank grain and its product samples varied from 84.2% to
      114.5%, with the relative standard deviations (RSDs) of 0.4%-9.9% (n=6). The
      method is accurate, efficient, sensitive and practical.

PMID- 29048787
TI  - [Rapid determination of benzo[a]pyrene in foods by ultra performance liquid
      chromatography-triple quadrupole mass spectrometry with atmospheric pressure
      chemical ionization].
AB  - A method for the determination of benzo[a]pyrene in foods was developed by ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based on
      isotope dilution and molecularly imprinted solid-phase extraction (MIP-SPE). The
      target analyte in samples was extracted with n-hexane after spiked with
      benzo[a]pyrene-d12, and purified using MIP-SPE to eliminate most of the
      coextracts. The separation of benzo[a]pyrene was carried out on an XBridge BEH
      C18 column with gradient elution of methanol and water. An atmospheric pressure
      chemical ionization (APCI) interface was used as the ion source and the analysis
      was performed in the multiple reaction monitoring (MRM) mode. Benzo[a]pyrene
      levels in the range of 0.07-50 MUg/kg were measured accurately by this method,
      and the limit of quantification (LOQ) was 0.07 MUg/kg. The average recoveries
      were between 86% and 104% with the relative standard deviations within 2.3%-14%.
      The method was sensitive and accurate, and it has been successfully applied to
      the measurement of benzo[a]pyrene in food samples.

PMID- 29048788
TI  - [Determination of amanitins and phallotoxins in wild mushrooms by online liquid
      chromatography-diode array detector-tandem mass spectrometry].
AB  - A fast and wide linear range method was established for the determination of
      mushroom toxins amanitins (alpha-amanitin,beta-amanitin and gamma-amanitin) and
      phallotoxins (phallacidin and phalloidin) in wild mushrooms by online liquid
      chromatography-diode array detector-tandem mass spectrometry (LC-DAD-MS/MS). The
      mushroom toxins were extracted with methanol, and diluted with water. The
      extracts were separated on an XBridgeTM BEH C18 column (150 mm*3.0 mm, 2.5 MUm)
      under pH 10.7, measured by DAD and then analyzed by MS/MS. Basic mobile phase
      conditions were applied to improve the ionization efficiency of hydrogen ion
      adducts. The baseline separation of the analytes was obtained within 15 min. The
      limits of detection (LODs) of the sample matrix were 0.005-0.02 mg/kg. The toxins
      were quantified by the results measured by MS/MS when the toxin contents less
      than 2 mg/kg, and quantified by the results obtained from DAD when the contents
      more than 2 mg/kg. The linear range was 0.05-500 mg/kg for the whole method in
      one injection. The method was successfully applied to the analyses of amanitins
      and phallotoxins in Lepiota brunneoincarnata and white Amanita.

PMID- 29048789
TI  - [Simultaneous determination of pyraclostrobin and thiophanate-methyl and its
      metabolite carbendazim residues in soil and citrus by QuEChERS-liquid
      chromatography- tandem mass spectrometry].
AB  - A QuEChERS-liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was
      developed for the determination of pyraclostrobin, thiophanate-methyl and its
      metabolite carbendazim in soil and citrus. The samples were extracted with
      methanol or acetonitrile, purified by primary secondary amine (PSA), then
      separated by LC, detected in multiple reaction monitoring (MRM) mass spectrometry
      mode via positive electrospray ionization. The analytes were quantified by matrix
      matched standard solutions with external standard method. The limits of
      quantification (LOQs) of pyraclostrobin, thiophanate-methyl and carbendazim in
      different matrices were 5.8-7.0 MUg/kg, 9.3-14.1 MUg/kg and 2.1-2.6 MUg/kg,
      respectively. For all the samples, the spiked recoveries ranged from 75.48% to
      109.18%, and the relative standard deviations (RSDs) were 0.60%-5.11% (n=5). The
      method is quick, easy, effective, sensitive and accurate. The matrix-matched
      calibration solutions can efficiently compensate matrix effects of the
      pyraclostrobin, thiophanate-methyl and carbendazim in LC-MS/MS analysis. The
      established method can be applied to the residue analysis of the real samples of
      soil, citrus peel, citrus pulp and citrus fruits.

PMID- 29048790
TI  - [Simultaneous determination of 30 mycotoxins in different feed products by ultra
      high performance liquid chromatography-tandem mass spectrometry].
AB  - A method for the simultaneous determination of 30 mycotoxins in different feed
      products was developed using a QuEChERS pretreatment procedure coupled with ultra
      high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
      The samples were extracted with 5 mL water and 5 mL acetonitrile containing 1%
      (v/v) formic acid. An aliquot of the supernatant was dried by nitrogen gas, re
      dissolved by 1mL water containing 5 mmol/L ammonium acetate-acetonitrile (80:20,
      v/v), and analyzed by UHPLC-MS/MS. Matrix-matched calibration curves and internal
      standards were used for accurate quantification. Satisfactory recoveries at low,
      medium and high spiked levels were ranged from 72.0% to 118.4% (n=5). Good linear
      relationships were obtained, the correlation coefficients (r2) were greater than
      0.99. The limits of detection (LODs, S/N=3) and the limits of quantification
      (LOQs, S/N=10) ranged from 0.7 MUg/L to 20 MUg/L and from 2 MUg/L to 50 MUg/L,
      respectively. The proposed method is simple, rapid and valuable, which can be a
      powerful tool for quantitative analysis of the 30 mycotoxins in premixed feed,
      concentrated feed and formula feed products.

PMID- 29048791
TI  - [An improvement of the calibration results for grey analytical system in high
      performance liquid chromatography applying constrained background bilinearization
      method based on genetic algorithm optimization strategy].
AB  - Constrained background bilinearization (CBBL) method was applied for multivariate
      calibration analysis of the grey analytical system in high performance liquid
      chromatography (HPLC). By including the variables of the concentrations and the
      retention time of the analytes simultaneously, the standard CBBL was modified for
      the multivariate calibration of the HPLC system with poor retention precision.
      The CBBL was optimized globally by genetic algorithm (GA). That is to say, both
      the concentrations and the retention times of the analytes were optimized
      globally and simultaneously by GA. The modified CBBL was applied in the
      calibration analysis for both simulated and experimental HPLC system with poor
      retention precision. The experimental data were collected from HPLC separation
      system for phenolic compounds. The modified CBBL was verified to be useful to
      prevent the inherent limitation of the standard CBBL, which means that the
      standard CBBL may result in poor calibration results in the case of poor
      retention precision in chromatography system. Moreover, the modified CBBL can
      give not only the concentrations but also the retention time of the analytes. i.
      e., more useful information of the analytes can be generated by the modified
      CBBL. Subsequently, nearly ideal calibration results were obtained. On the other
      hand, comparing with the calibration results by the classical rank annihilation
      factor analysis (RAFA) and residual bilinearization (RBL) method, the results
      given by the modified CBBL were also improved significantly for the HPLC systems
      studied in this work.

PMID- 29048792
TI  - [A novel pattern for predicting the quality of Chinese herba preparation
      intelligently by high performance liquid chromatographic formula fingerprints].
AB  - In order to build the fusion models, the high performance liquid chromatographic
      (HPLC) fingerprints of scutellariae radix (SR), rhei radix et rhizoma (RRR),
      coptidis rhizoma (CR) and their synthesizing fingerprints were developed in this
      study. After exploring the consistency between the fingerprints of compound
      synthesizing fingerprints (CSF) and the sample, the quality of traditional
      Chinese medicine preparation was predicted intelligently using CSF. HPLC coupled
      with diode array detector was used to obtain chromatograms of SR, RRR, CR and Yi
      Qing Tablet (YQT) samples at 268 nm. Meanwhile, the quality of CSF and the 15
      batches of YQT samples was evaluated by systematically quantified fingerprint
      method (SQFM) qualitatively and quantitatively. The chromatograms showed that CSF
      covered the main fingerprints' information of each herb and the 55 common peaks
      of CSF covered the main information of the 50 common peaks in YQT sample. The
      evaluation results showed that among the 15 batches of YQT samples, only YQT-S01
      was grade 5 and the others were all above grade 3. Most of the CSFs were grade 2
      or grade 1 except CSF-2 which was grade 6. The fingerprints of Chinese herba
      preparation could be replaced by CSF to achieve a novel pattern for predicting
      the quality of TCM preparation intelligently by studying the relationship between
      the standard fingerprints and the CSF, and simultaneously developing first-class
      evaluation software.

PMID- 29048793
TI  - [Separation and purification of the components in Trachelospermum jasminoides by
      two dimensional hydrophilic interaction liquid chromatography- reversed-phase
      liquid chromatography].
AB  - A preparative two dimensional hydrophilic interaction liquid
      chromatography/reversed-phase liquid chromatography (Pre-2D-HILIC/RPLC) method
      was established to separate and purify the components in Trachelospermum
      jasminoides. The pigments and strongly polar components were removed from the
      crude extract after the active carbon decolorization and solid phase extraction
      processes. A Click XIon column (250 mm*20 mm, 10 MUm) was selected as stationary
      phase and water-acetonitrile as mobile phases in the first dimensional HILIC.
      Finally, 15 fractions were collected under UV-triggered mode. In the second
      dimensional RPLC, a C18 column (250 mm*20 mm, 5 MUm) was selected and water
      acetonitrile was used as mobile phases. As a result, 14 compounds with high
      purity were obtained, which were further identified by mass spectrometry (MS) and
      nuclear magnetic resonance (NMR). Finally, 11 lignan compounds and three
      flavonoid compounds were obtained. The method has a good orthogonality, and can
      improve the resolution and the peak capacity. It is significant for the
      separation of complex components from Trachelospermum jasminoides.

PMID- 29048794
TI  - [Ionic liquid based ultrasonication-assisted extraction of essential oil from the
      leaves of Persicaria minor and conductor-like screening model for realistic
      solvents study].
AB  - Ionic liquids (ILs) based ultrasonic-assisted extract has been applied for the
      extraction of essential oil from Persicaria minor leaves. The effects of
      temperature, sonication time, and particle size of the plant material on the
      yield of essential oil were investigated. Among the different ILs employed, 1
      ethyl-3-methylimidazolium acetate was the most effective, providing a 9.55% yield
      of the essential oil under optimum conditions (70 C, 25 min, IL:hexane ratio of
      7:10 (v/v), particle size 60-80 mesh). The performance of 1-ethyl-3
      methylimidazolium acetate in the extraction was attributed to its low viscosity
      and ability to disintegrate the structural matrix of the plant material. The
      ability of 1-ethyl-3-methylimidazolium acetate was also confirmed using the
      conductor like-screening model for realistic solvents. This research proves that
      ILs can be used to extract essential oils from lignocellulosic biomass.

PMID- 29048795
TI  - [Determination of residual toluene diisocyanate in sponge bra by gas
      chromatography].
AB  - A gas chromatography (GC) with internal standard method was developed for the
      determination of residual toluene diisocyanate (TDI) in sponge bra. The samples
      were extracted with ethyl acetate dehydrated, and cleaned up with 0.22 MUm
      microfiltration membrane. The residual toluene diisocyanate was separated on a DB
      624 capillary column using temperature programming. The flame ionization detector
      (FID) was used at 250 C. The inlet temperature was 180 C with nitrogen as carrier
      gas. The linear range was 10-200 mg/L (R2=0.9989) for TDI. The average recovery
      ranged from 80.5% to 91.6% with RSD not more than 7.9%(n=6). The limit of
      detection (LOD) and limit of quantification (LOQ) were 10 mg/kg and 100 mg/kg,
      respectively. The developed method was then utilized to analyse the 100 batches
      of sponge bra samples from the manufacturing enterprises, the entity shops and
      electric business platforms. The method is simple, time-saving and environment
      friendly with high sensitivity and good reproducibility, and has practical
      application value due to its low-cost and short-circle.

PMID- 29048796
TI  - [Determination of polycyclic aromatic hydrocarbons in airborne particles by
      microwave extraction-high performance liquid chromatography].
AB  - A method by using microwave extraction and high performance liquid chromatography
      was developed to determine polycyclic aromatic hydrocarbons (PAHs) in airborne
      particles. The glass/quartz fiber filter, on which particles adsorbed, was
      extracted with a mixed solvent n-hexane/acetone (1:1, v/v) using microwave, and
      the subsequent purification of the extract was carried out by a florisil
      cartridge. The prepared sample was determined by high performance liquid
      chromatography coupled with photodiode array (PDA) and fluorescence dual
      detector. The target compounds showed good linearity between the mass
      concentration of 20.0 MUg/L and 500 MUg/L, with the correlation coefficients not
      less than 0.9960. The spiked recoveries of target compounds in blank filter
      ranged from 56.3%-101%. The current method has been applied to investigate the
      distribution of PAHs in airborne particles in Nanjing City.

PMID- 29048797
TI  - [Hydrogen isotopes analysis by gas chromatography using metal-organic framework
      CPL-1 packed column].
AB  - CPL-1 is a metal organic framework (MOF) with potential application as stationary
      phase material in gas chromatographic (GC) analysis, due to its large specific
      surface area, uniform pore size and good quantum sieving effect on hydrogen
      isotopes at low temperatures. Herein, a microporous column packed with CPL-1 was
      used at cryogenic temperature (77 K), and the column was 1.0 mm in inner
      diameter, 0.5 m in length. Single crystals of Al2O3 was used to build flow path
      for chromatographic carrier gas. The results showed that the adsorption of H2 and
      D2 with CPL-1 was 4 mmol/g at 77 K, which was better than MnCl2/gamma -Al2O3 and
      gamma -Al2O3. With the injection volume increasing from 0.25 mL to 2 mL, the
      results showed good linear relationship, and the relative error was less than 4%.
      The results indicated that the column packed with CPL-1 has wide linear range,
      good repeatability and high accuracy, and it has potential use in hydrogen
      isotope analysis with gas chromatography.

PMID- 29048798
TI  - [Comparison of CIM(r) C4-HLD monolithic column with Sartobind phenyl membrane
      column for pIDKE2 purification].
AB  - The main component of the Center for Genetic Engineering and Biotechnology (CIGB)
      candidate vaccine against Hepatitis C virus (HCV) is the pIDKE2 plasmid.The
      current designed downstream process for the production of pIDKE2 fulfils all
      regulatory requirements and renders the required quantities of pharmaceutical
      grade plasmid DNA (pDNA) with 95% purity.The advantages of this procedure include
      high plasmid purity and the elimination of undesirable additives,such as toxic
      organic extractants and animal-derived enzymes.However,yields and consequently
      the productivity of the process are low.Previous work demonstrated that the most
      critical step of the process is the reverse phase chromatography,where
      conventional porous particle resins are used.Therefore,to increase the process
      productivity,alternative technologies such as membranes and chromatographic
      monoliths were tested as alternative options for this critical step.Here,a
      comparison between the behaviors of CIM(r) C4-HLD and Sartobind phenyl matrices
      was performed.To obtain higher productivities and purities,the dynamic binding
      capacities and selectivities were evaluated.The results showed that both matrices
      had a similar capacity for pIDKE2 plasmid,but the separation of pDNA isoforms
      using CIM technology was much better than that with Sartobind.Additionally,the
      optimal conditions for loading plasmid DNA on a CIM(r) C4-HLD 800-mL monolithic
      column in a real production process were determined.These optimizations will
      allow production levels to satisfy the high plasmid consumption demanded by
      clinical trials.

PMID- 29048799
TI  - [High-sensitive detection of multiple allergenic proteins in infant food with
      high-resolution mass spectrometry].
AB  - A novel method of the simultaneous detection of multiple kinds of allergenic
      proteins in infant food with parallel reaction monitoring (PRM) mode using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) was established. In this
      method, unique peptides with good stability and high sensibility were used to
      quantify the corresponding allergenic proteins. Furthermore, multiple kinds of
      allergenic proteins are inspected simultaneously with high sensitivity. In
      addition, such method was successfully used for the detection of multiple
      allergenic proteins in infant food. As for the sample preparation for infant
      food, compared with the traditional acetone precipitation strategy, the protein
      extraction efficiency and capacity of resisting disturbance are both higher with
      in-situ filter-aided sample pretreatment (i-FASP) method. All allergenic proteins
      gave a good linear response with the correlation coefficients (R2) >= 0.99, and
      the largest concentration range of the allergenic proteins could be four orders
      of magnitude, and the lowest detection limit was 0.028 mg/L, which was better
      than that reported in references. Finally, the method was conveniently used to
      detect the allergens from four imported infant food real samples. All the results
      demonstrate that this novel strategy is of great significance for providing a
      rapid and reliable analytical technique for allergen proteomics.

PMID- 29048800
TI  - [Determination of urine catecholamines and metanephrines by reversed-phase liquid
      chromatography-tandem mass spectrometry].
AB  - The measurement of urine catecholamine and metanephrine concentrations is
      important for biochemical screening and diagnosis of pheochromocytoma. The goal
      of this work was to develop a simple liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for determining catecholamines and metanephrines
      in urine to replace an existing liquid chromatographic method using
      electrochemical detection. Urine samples were prepared using Oasis weak-cation
      exchange cartridges. The eluate was analyzed on an Agilent ZORBAX Eclipse Plus
      Phenyl-Hexyl column in 3 min. Adrenaline, noradrenaline, dopamine, metanephrine,
      normetanephrine, and their deuterated internal standards were monitored in
      positive electrospray ionization mode by multiple reaction monitoring (MRM). No
      evidence of ion suppression was observed. The assay was linear up to 5MUmol/L for
      adrenaline, 5MUmol/L for noradrenaline, 6.1MUmol/L for dopamine, 5.6MUmol/L for
      metanephrine, and 34.6MUmol/L for normetanephrine, with lower limits of
      quantification of 5, 5, 12, 6 and 7 nmol/L, respectively. The intra-day and inter
      day precisions for all analytes ranged from 0.59% to 4.64% and 1.98% to 4.80%,
      respectively. External quality assurance samples were assayed and showed
      excellent agreement with the target values. This simple method provides an
      improved assay for determining urine catecholamines and metanephrines.

PMID- 29048801
TI  - [Determination of thyreostats in bovine urine using ultra-high performance liquid
      chromatography-tandem mass spectrometry].
AB  - Five thyreostats (TSs), namely tapazole, thiouracil, methylthiouracil,
      propylthiouracil, and phenylthiouracil, were determined in bovine urine using
      ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC
      MS/MS) in positive electrospray ionization mode. Extraction and clean-up were
      achieved using a ChemElut cartridge with tert-butyl methyl ether, without a
      derivatization step. Separation was achieved on an Acquity UPLC SS T3 column. The
      mobile phase was acetonitrile and water containing 0.2% (v/v) formic acid. The
      mass spectrometer was operated in multiple reaction monitoring mode. Urine
      samples were spiked with TS solution at levels corresponding to 5, 10, 15, and 20
      MUg/L. The accuracy (internal standard corrected) ranged from 92% to 107%, with a
      repeatability precision (relative standard deviation, RSD) less than 15% for all
      five analytes. The RSDs within-laboratory reproducibility was less than 26%. The
      decision limits (CCalpha) and detection capabilities (CCbeta) were obtained from
      a calibration curve and were in the ranges of 3.1-6.1 MUg/L and 4.0-7.4 MUg/L,
      respectively. The CCalpha and CCbeta values were below the recommended
      concentration, which was set at 10 MUg/L. The results show that the described
      method is suitable for the direct detection of TSs in bovine urine. This method
      can also be used to determine TSs in porcine urine.

PMID- 29048802
TI  - [Liquid chromatography-tandem mass spectrometry method for determination of 10
      macrolide antibiotics in pork samples using on-line solid phase extraction
      purification].
AB  - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      method based on-line solid phase extraction (SPE) purification was established to
      determine 10 macrolide antibiotics in pork samples. The samples were extracted
      with acetonitrile, and the extracts were dried with rotary evaporator at 40C,
      then the analytes were dissolved with 2 mL phosphate buffer. The solutions were
      purified and concentrated by on-line SPE with HLB cartridges. The analytes were
      eluted with methanol, and then transferred to XBridge BEH C18 column, separated
      with the mobile phases of 10 mmol/L ammonium acetate aqueous solution and
      acetonitrile. Finally, the target analytes were detected by tandem mass
      spectrometry. The results showed that good linearity was obtained in the range of
      0.1-200 MUg/L for the 10 macrolide antibiotics with correlation coefficients
      better than 0.990. The limits of detection were in range of 0.05-0.30 MUg/kg and
      the limits of quantitation were in range of 0.10-1.00 MUg/kg. The recoveries of
      the method were in range of 69.6%-115.2% at the spiked levels of 0.10-10.0 MUg/kg
      for all analytes, with the relative standard deviations less than 10%. The
      developed method can be used for the determination of the 10 macrolide
      antibiotics in pork samples.

PMID- 29048803
TI  - [Determination of imidazoles and their metabolites in pork by liquid
      chromatography-tandem mass spectrometry].
AB  - A method for the determination of 29 imidazoles and their metabolites in pork by
      liquid chromatography-tandem mass spectrometry has been developed. The samples
      were extracted with ethyl acetate, and then defatted with n-hexane after
      concentration of the extracts. The analytes were separated on a C18 reversed
      phase column with 0.3% (v/v) formic acid aqueous solution and acetonitrile as
      mobile phases, and finally analyzed using electrospray ionization in positive ion
      mode (ESI+) with multiple reaction monitoring (MRM). The linear ranges of the 29
      compounds were from 0.05 to 20.0 MUg/L with the correlation coefficients (r2)
      more than 0.99. The average recoveries and relative standard deviations were
      65.4%-103% and 1.3%-6.8% respectively in the spiked ranges of 1.0-5.0 MUg/kg. The
      limits of detection and the limits of quantification were 0.02-0.3 MUg/kg and 0.1
      1 MUg/kg respectively for the 29 imidazoles. The method is simple, rapid and
      sensitive. It is suitable for the detection of imidazoles and their metabolites
      in pork.

PMID- 29048804
TI  - [Determination of characteristic compound in manuka honey by automatic on-line
      solid phase extraction-liquid chromatography-high resolution mass spectrometry].
AB  - A method for the determination of characteristic compound 3,5-dimethoxybenzoate-4
      diglucoside (leptosperin) in manuka honey was developed by automatic on-line
      solid phase extraction-liquid chromatography-high resolution mass spectrometry
      (SPE-LC-HRMS). The samples were separated on a Dikma Diamonsil Plus C18 column
      (150 mm*4.6 mm, 5 MUm) using the mobile phases of 0.1% (v/v) formic acid aqueous
      solution and acetonitrile with gradient elution. The compound was detected with
      negative electrospray ionization (ESI-) in Target-MS2 mode. The results showed
      that the linear range was 0.5-100.0 mg/L, the correlation coefficient was 0.9993.
      The limit of detection (LOD, S/N >= 3) and limit of quantification (LOQ, S/N >=
      10) of the method was 3 mg/kg and 10 mg/kg, respectively. The recoveries at the
      spiked levels of 50.0, 100.0, 200.0 mg/kg (10.0, 20.0, 50.0 mg/kg in black locust
      samples) were in the range of 82.0%-95.2% with the relative standard deviations
      ranging from 2.7% to 9.7% (n=6). The proposed method was applied to 95 mature
      honey samples from hives in New Zealand including 12 different kinds and 50
      commercial honey samples from four different countries. The method is fast,
      sensitive and accurate to provide technical support to solve the judgment of the
      manuka honey imported from New Zealand.

PMID- 29048805
TI  - [Simultaneous determination of nine perfluorinated compound precursors in
      atmospheric precipitation by solid phase extraction and ultra performance liquid
      chromatography with tandem mass spectrometry].
AB  - A high-throughput detection method has been developed for the determination of
      nine perfluorinated compound precursors (PFCPs) in atmospheric precipitation by
      solid phase extraction-ultra performance liquid chromatography coupled with
      electrospray ionization tandem mass spectrometry (SPE-UPLC-ESI-MS/MS). The
      atmospheric precipitation samples were concentrated and purified with HLB solid
      phase extraction cartridges. The UPLC separation was performed on an HSS T3
      column (100 mm*2.1 mm, 1.7 MUm) utilizing a gradient elution program of methanol
      and water as the mobile phases at a flow rate of 0.2 mL/min. The MS/MS detection
      was performed under negative electrospray ionization (ESI-) in multiple reaction
      monitoring (MRM) mode. Good linearity was observed in the range of 0.05-5.00
      MUg/L, 0.50-50.0 MUg/L or 5.00-500 MUg/L with correlation coefficients from
      0.9921 to 0.9995. The limits of detection (LODs) for the nine perfluorinated
      compound precursors were in the ranges of 0.05-7.9 ng/L. The recoveries ranged
      from 76.0% to 106% with the relative standard deviations between 0.72% and 13.7%.
      This method is characterized by high sensitivity and precision, extensive
      analytical range and quick analytical rate, and can be applied for the analysis
      of perfluorinated compound precursors in atmospheric precipitation.

PMID- 29048806
TI  - [Determination of hexabromocyclododecanes in ambient air by high performance
      liquid chromatography- electrospray ionization-mass spectrometry].
AB  - A high performance liquid chromatography-electrospray ionization-mass
      spectrometry (HPLC-ESI-MS) method was developed for the determination of
      hexabromocyclododecanes (HBCDs) in ambient air samples. The samples were
      extracted by Soxhlet extractor with hexane, then purified on the composite gel
      column. At first, the interfering substances were rinsed with 50 mL hexane and
      100 mL hexane-dichloromethane (9:1, v/v), then 180 mL hexane -dichloromethane
      (4:1, v/v) was used to elute the targets. The compounds were separated by
      gradient elution with acetonitrile-methanol-water as mobile phases on a UF-ODS
      column (150 mm*2.1 mm, 3.0 MUm). Electrospray ionization negative ion source and
      selective ion monitoring (SIM) mode were adopted in MS detection. The results
      showed that alpha -HBCD, beta -HBCD and gamma -HBCD could be well separated, and
      the chromatographic peak area ratio of alpha -HBCD, beta -HBCD and gamma -HBCD to
      internal standard D18- gamma -HBCD with their concentrations had a good linear
      relationship, with the correlation coefficients (R) >= 0.9988. The limits of
      detection (LODs, S/N=3) of alpha -HBCD, beta -HBCD and gamma -HBCD were 0.4, 0.5
      and 0.4 MUg/L, respectively. The limits of quantification (LOQs, S/N=10) were
      1.4, 1.6 and 1.3 MUg/L, respectively. The method detection limits (MDL) were
      0.13, 0.17 and 0.13 pg/m3 (n=5), respectively. The recoveries of HBCDs spiked in
      the actual air samples were in the range of 74.8%-95.8%. It is demonstrated that
      the method has high sensitivity and good selectivity, and can meet the
      requirement of monitoring and analyzing HBCDs in air samples.

PMID- 29048807
TI  - [Rapid determination of 10 volatile N-nitrosamines in sour meats by modified
      QuEChERS and gas chromatography- triple quadrupole mass spectrometry].
AB  - A rapid gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) method
      with modified QuEChERS method was developed for the determination of 10 volatile
      N-nitrosamines in sour meats. The samples were extracted with acetonitrile and
      eliminated the fat with n-hexane. The extracts in acetonitrile layer were
      purified by octadecyl silane (C18) and primary secondary amine (PSA) sorbents.
      The N-nitrosamines were determined on a DB-WAX column (30 m*0.25 mm*0.25 MUm) by
      GC-MS/MS in selected reaction monitoring (SRM) mode. The external standard method
      was used to quantify the N-nitrosamines. The correlation coefficients (r) of the
      standard calibration curves were greater than 0.99 in the range of 1-100 MUg/L.
      The average recoveries ranged from 79.8% to 115.3% with the relative standard
      deviations (RSDs) from 0.6% to 22.9% (n=6). The limits of detection (LODs, S/N=3)
      and limits of quantification (LOQs, S/N=10) were 0.04-0.3 MUg/kg and 0.1-1
      MUg/kg, respectively. The developed method is simple, rapid, sensitive and
      efficient for the screening of the N-nitrosamines in sour meats.

PMID- 29048808
TI  - [Target and non-target screening of volatile organic compounds in industrial
      exhaust gas using thermal desorption-gas chromatography-mass spectrometry].
AB  - A method of comprehensive screening of the target and non-target volatile organic
      compounds (VOCs) in industrial exhaust gas using thermal desorption-gas
      chromatography-mass spectrometry (TD-GC-MS) has been developed. In this paper,
      two types of solid phase adsorption column were compared, and the Tenex SS TD
      Tube was selected. The analytes were enriched into the adsorption tube by
      constant flow sampling, and detected by TD-GC-MS in full scan mode. Target
      compounds were quantified by internal standard method, and the quantities of non
      target compounds were calculated by response coefficient of toluene. The method
      detection limits (MDLs) for the 24 VOCs were 1.06 to 5.44 ng, and MDLs could also
      be expressed as 0.004 to 0.018 mg/m3 assuming that the sampling volume was 300
      mL. The average recoveries were in the range of 78.4% to 89.4% with the relative
      standard deviations (RSDs) of 3.9% to 14.4% (n=7). The established analytical
      method was applied for the comprehensive screening of VOCs in a waste
      incineration power plant in Dalian city. Twenty-nine VOCs were identified. In
      these compounds, only five VOCs were the target compounds set in advance, which
      accounted for 26.7% of the total VOCs identified. Therefore, this study further
      proved the importance of screening non-target compounds in the analysis of VOCs
      in industrial exhaust gas, and has certain reference significance for the
      complete determination of VOCs distribution.

PMID- 29048809
TI  - [Determination of guanidinoacetic acid in feed by ion chromatography coupled with
      ultraviolet detection].
AB  - A novel ion chromatography method for the determination of guanidinoacetic acid
      (GAA) in animal feed samples was developed. The optimal detection mode,
      chromatography column, gradient condition of mobile phases and sample
      pretreatment conditions were investigated. Using a linear gradient of methane
      sulfonic acid and ultraviolet detector at 200 nm, the interfering substances in
      feed samples and GAA could be separated successfully on a Dionex IonPacTM CS16
      cation exchange analysis column. The calibration curves showed a range of
      linearity between 0.5 and 200 mg/L, and a high linear regression coefficient of
      0.9999 was obtained for GAA. The limits of detection and limits of quantification
      of GAA in formula feed and concentrate feed were 4.5 and 15 mg/kg, respectively.
      The limit of detection and limit of quantification of GAA in compound-premix were
      9.0 and 30 mg/kg, respectively. The recoveries of this method for GAA were
      investigated, and the recoveries were all more than 94% in formula feed,
      concentrate feed and compound-premix feed for pig and poultry. This method can
      meet the requirements of the determination of GAA in feed samples for the feed
      production enterprise and evaluation center.

PMID- 29048810
TI  - [Simultaneous determination of 15 polycyclic aromatic hydrocarbons in cigarette
      filter by gas chromatography-tandem mass spectrometry].
AB  - A method for the simultaneous determination of 15 polycyclic aromatic
      hydrocarbons in cigarette filter was developed by isotope internal standard
      combined with gas chromatography-tandem mass spectrometry. The cigarette filters
      were extracted with dichloromethane, and the extract was filtered with 0.22 MUm
      organic phase membrane. The samples were isolated by DB-5MS column (30 m*0.25 mm,
      0.25 MUm) and detected using multiple reaction monitoring mode of electron impact
      source under positive ion mode. The linearities of the 15 polycyclic aromatic
      hydrocarbons (acenapthylene, acenaphthene, fluorene, phenanthrene, anthracene,
      fluoranthene, pyrene, ben[a]anthracene, chrysene, benzo[b]fluoranthene,
      benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a,h]anthracene,
      benzo[g,h,i]perylene and indeno[1,2,3-c,d]pyrene) were good, and the correlation
      coefficients (R2) ranged from 0.9914 to 0.9999. The average recoveries of the 15
      polycyclic aromatic hydrocarbons were 81.6%-109.6% at low, middle and high spiked
      levels, and the relative standard deviations were less than 16%, except that the
      relative standard deviation of fluorene at the low spiked level was 19.2%. The
      limits of detection of the 15 polycyclic aromatic hydrocarbons were 0.02 to 0.24
      ng/filter, and the limits of quantification were 0.04 to 0.80 ng/filter. The
      method is simple, rapid, accurate, sensitive and reproducible. It is suitable for
      the quantitative analysis of the 15 polycyclic aromatic hydrocarbons in cigarette
      filters.

PMID- 29048811
TI  - [Rapid screening of pesticide residues in imported grains by ultra-performance
      liquid chromatography-quadrupole-time of flight mass spectrometry].
AB  - A fast sample pretreatment method by fast pesticide extraction (FaPEx) method
      combined with ultra-performance liquid chromatography-quadrupole-time of flight
      mass spectrometry was developed for screening of unknown pesticide residues in
      imported grains. The samples were extracted with 1% (v/v) acetic acid
      acetonitrile solution, cleaned-up by solid phase extraction column with FaPEx
      cartridges, and determined by UPLC-Q-TOF. The data was compared with the library
      with the accurate mass, isotopic distribution, fragmentation information and
      retention time. The results showed that this method can be used for the rapid
      screening of pesticide residues in imported grains without the reference
      standards, and it was applied to the actual screening of imported grain samples.
      The method is high efficiency, sensitivity and accuracy, which can meet the
      requirement for the rapid screening of pesticide residues in imported grains.

PMID- 29048812
TI  - [Rapid and simultaneous determination of seven microcystins in fish meat by
      liquid chromatography-tandem mass spectrometry coupled with pass-through solid
      phase extraction].
AB  - An analytical method was developed for the simultaneous and rapid determination
      of seven microcystins in fish meat by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) coupled with pass-through solid phase extraction (SPE).
      The samples were extracted with methanol-water (90:10, v/v) after heat treatment
      by water bath at 80C, and then cleaned up with an Oasis PRiME HLB pass-through
      SPE column. The samples were analyzed directly on a Waters XSelect HSS T3 column
      using 0.1% (v/v) aqueous formic acid and acidified acetonitrile (0.1% formic
      acid, v/v) as mobile phases. Qualitative and quantitative analysis of the
      analytes was carried out under the multiple reaction monitoring mode with
      positive electrospray ionization. The matrix matching external standard method
      was used for quantitation analysis. To solve the problem of parent ion selection
      of the microcystins, the ionization characteristics of microcystins were
      evaluated under different mobile phase conditions. Finally, the results showed
      that the acid could promote the intensity of the doubly charged ions
      significantly. The calibration curves were linear well in the corresponding
      concentration ranges, with correlation coefficient >= 0.99. The limits of
      quantification ranged from 0.30 to 2.0 MU g/kg. The average spiked recoveries for
      the seven microcystins were between 70.6% and 96.1% with the relative standard
      deviations of 3.4%-9.6%. The proposed method is sensitive, accurate, and
      efficient. It is applicable for the determination of microcystins in fish meat.

PMID- 29048813
TI  - [Determination of three tranquillizer residues in animal foods by QuEChERS-high
      performance liquid chromatography-tandem mass spectrometry].
AB  - A method for simultaneous determination of chlorpromazine, diazepam and
      metolazone residues in porcine muscle, fish, liver and kidney was developed using
      QuEChERS and HPLC-MS/MS technique. The samples were extracted with ethyl acetate
      and cleaned up with C18, N-propylethylendiamine (PSA) and NH2 sorbents after
      using Na2SO4 as dehydrating agent. The analytes were separated by a special C18
      column, Atlantis T3, and gradiently eluted with a mixed solution of 5 mmol/L
      formic acid and acetonitrile at a flow rate of 0.35 mL/min. The mass
      spectrometric analysis that quantified using isotope internal standard, was
      carried out with electrospray positive ion source (ESI+) and multiple reaction
      monitoring mode (MRM). The linearity of the calibration curves was good in the
      range of 0.2-5.0 MU g/L. The recoveries at three different spiked levels (0.5, 1
      and 5 MU g/kg) in four matrices were in the range of 92.5%-117.8%. The
      repeatability expressed as relative standard deviations (RSDs) ranged from 0.7%
      to 11.6% (n=6). The method, with wide matrix range of application, is highly
      effective and sensitive and suitable for the rapid analysis of large quantities
      of samples.

PMID- 29048815
TI  - [Simultaneous rapid determination of 81 glucocorticoids in cosmetics by
      dispersive solid phase extraction and liquid chromatography-tandem mass
      spectrometry].
AB  - A novel method was developed for the simultaneous rapid determination of 81
      illegally added glucocorticoids (GCs) in cosmetics using dispersive-solid phase
      extraction (d-SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      The analytes were extracted by acetonitrile after dispersing with water, and then
      purified using the C18 and primary secondary amine (PSA). The chromatographic
      separations were performed on a Poroshell 120 PFP column (100 mm*2.1 mm, 2.7 MU
      m) under multiple chromatographic retention modes. Acetonitrile and 0.2% (v/v)
      acetic acid aqueous solution were used as mobile phases with gradient elution,
      and all the 10 groups of isomers were baseline separated. The qualitative
      identification and quantitative analysis of the 81 GCs were operated in the
      electrospray ionization positive mode using dynamic multiple reaction monitoring
      (DMRM). The 81 GCs finally were quantified by internal standard method. The
      correlation coefficients of linear calibration curves were greater than 0.99 in
      the corresponding mass concentration ranges. The average recoveries of the 81 GCs
      at three spiked levels ranged from 68.8% to 105.3% with relative standard
      deviations (RSDs) of 2.9%-13.1% (n=6). The LODs (S/N >= 3) and LOQs (S/N >= 10)
      were 0.002-0.006 MU g/g and 0.005-0.020 MU g/g, respectively. A number of 137
      cosmetic samples submitted by customers were screened. Sixteen positive samples
      were found, and the contents of GCs were from 16.9 MU g/g to 158 MU g/g. The
      results showed that the new method is simple, rapid, sensitive and reliable, and
      it is suitable for qualitative and quantitative screening analysis of the 81 GCs
      in cosmetics simultaneously.

PMID- 29048814
TI  - [Determination of 11 mycotoxins in baked foods and raw materials by ultra
      performance liquid chromatography-quadrupole/electrostatic field orbitrap high
      resolution mass spectrometry].
AB  - A method for the determination of 11 mycotoxins in baked foods and raw materials
      by ultra-high performance liquid chromatography-quadrupole/electrostatic field
      orbitrap high-resolution mass spectrometry (UPLC-HRMS) is reported in this paper.
      The samples were extracted with 20 mL 90% (v/v) acetonitrile aqueous solution
      containing 1% (v/v) formic acid, and the extracts were salted out by 2.0 g MgSO4
      and 0.5 g NaCl, cleaned up by 300 mg C18. The analytes were carried out on a
      CORTECS C18 column (100 mm*2.1 mm, 1.6 MU m) by gradient elution with 2 mmol/L
      ammonium acetate with 0.1% (v/v) formic acid aqueous solution and 2 mmol/L
      ammonium acetate methanol with 0.1% (v/v) formic acid. The results showed that
      the 11 mycotoxins had good linear relationships in their respective mass
      concentration ranges. The correlation coefficients were not less than 0.9960 and
      the limits of quantitation (LOQs) were from 0.15 to 20.00 MU g/kg. The recoveries
      of the 11 mycotoxins in bread ranged from 64.38% to 122.61% with the relative
      standard deviations (RSDs) from 1.52% to 12.99% at three spiked levels (n=6). The
      method is demonstrated to be simple, fast, highly sensitive, reliable and it is
      effective to detect common mycotoxins in baked foods and raw materials.

PMID- 29048816
TI  - [Determination of nicotine and cotinine in urine by hydrophilic interaction
      chromatography-tandem mass spectrometry].
AB  - The analytical method of nicotine and cotinine in human urine with hydrophilic
      interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) was
      established. After the urine sample containing nicotine-d4 and cotinine-d3
      isotope internal standards being diluted with water, the filtrate was introduced
      into ultra performance liquid chromatography-tandem mass spectrometry (UPLC
      MS/MS) for analysis. Separation was performed on an ACQUITY UPLC(r) BEH HILIC
      column (50 mm*3.0 mm, 1.7 MU m), in which methanol and 0.1% (v/v) ammonia were
      used as the mobile phases with isocratic elution at 0.2 mL/min of flow rate.
      Positive ion scan mode was used for mass spectrometry measurement and calibration
      curves were plotted for quantification determination. A good linearity could be
      obtained in the range of 1.0-1000 MU g/L for nicotine and cotinine with the
      linear coefficients of 0.9949 and 0.9958, respectively. The limits of detection
      of nicotine and cotinine were 0.082 MU g/L and 0.077 MU g/L, and the limits of
      quantification were 0.27 MU g/L and 0.26 MU g/L, respectively. The recoveries of
      the spiked urine samples were 90.4%-103.5% and 93.0%-104.6%, and the relative
      standard deviations (RSDs) were 4.80%-6.21% and 4.22%-7.15% for nicotine and
      cotinine respectively. The established method was applied to the analyis of 200
      urine samples. Based on the investigation information of the urine of the smoking
      people, the nicotine contents were 26.68-854.30 MU g/L, and the cotinine contents
      were 36.66-1191.18 MU g/L (n=86, Mnicotine=76.00 MU g/L, Mcotinine=83.52 MU g/L,
      M:median); of the nonsmoking people, the nicotine contents were 5.08-69.66 MU
      g/L, and the cotinine contents were 3.16-28.21 MU g/L (n=114, Mnicotine=7.53 MU
      g/L, Mcotinine=3.79 MU g/L). The method is simple, sensitive and rapid. It is
      suitable for batch analysis of nicotine and cotinine in urine, and it can meet
      the requirement of evaluating the human tobacco exposure.

PMID- 29048817
TI  - [Determination of five nucleotides in infant formula milk powder by modified high
      performance liquid chromatography].
AB  - A modified high performance liquid chromatographic (HPLC) method was developed
      for the determination of the five nucleotides (uridine monophosphate (UMP),
      adenosine monophosphate (AMP), inosine monophosphate (IMP), guanosine
      monophosphate (GMP) and cytidine monophosphate (CMP)) in infant formula milk
      powder. The samples were extracted by water, deproteinized by acetic acid and
      purified with an HLB SPE cartridge. The analytes were separated by a Waters
      XBrigde Amide column (150 mm*4.6 mm, 3.5 MU m). Acetonitrile, 10 mmol/L sodium
      dihydrogen phosphate aqueous solution and 0.12%(v/v) phosphoric acid aqueous
      solution were used as mobile phases with gradient elution. The detection
      wavelength of photodiode array detector was set at 254 nm. Five linear
      calibration curves were obtained with correlation coefficients (r2) of 0.9999.
      The recoveries were determined at three spiked levels ranging from 86.9% to
      105.7%. The limits of quantification (LOQs) were from 5.6 mg/kg to 8.0 mg/kg. The
      intra-day and inter-day precisions were 0.5%-1.7% (n=5) and 0.6%-1.9% (n=9),
      respectively. The method is simple, effective, accurate and repeatable. It is
      suitable for thedetermination of the five nucleotides in infant formula milk
      powder.

PMID- 29048818
TI  - [Determination of diacetyl in liquors by high performance liquid chromatography
      coupled with precolumn derivatization using 3,3'-diaminobenzidine].
AB  - A method was developed for the determination of diacetyl in liquors by high
      performance liquid chromatography-ultraviolet (HPLC-UV) coupled with precolumn
      derivatization using derivatization reagent 3,3'-diaminobenzidine (DAB). Diacetyl
      reacted with DAB at room temperature for 10 min. Then the separation was carried
      out on a high performance liquid chromatograph equipped with a diode array
      detector (DAD). A Shim-pack VP-ODS (250 mm*4.6 mm, 4.6 MU m) column was employed
      using water-methanol mobile phases for gradient at a flow rate of 0.7 mL/min and
      detection wavelength of 254 nm. The method showed a good linearity at diacetyl
      concentrations from 0.20 MU mol/L to 180 MU mol/L with the correlation
      coefficient (R2) of 0.999. The limit of detection (S/N=3) and limit of
      quantification (S/N=10) were 0.09 MU mol/L and 0.20 MU mol/L, respectively. The
      intra-day precision (RSD) was 1.28% (n=6). The method was further evaluated in
      the analysis of liquor samples with the recoveries ranging from 92.0% to 103.6%
      and RSDs from 0.69% to 3.45% (n=3). The method is well suitable for the
      measurement of diacetyl in liquor samples.

PMID- 29048819
TI  - [Determination of Pb2+ in tea by bis(salicylaldehyde)-o-phenylenediamine pre
      column derivatization-high performance liquid chromatography].
AB  - The contents of Pb2+ in tea was determined by the high performance liquid
      chromatography (HPLC) method using bis(salicylaldehyde)-o-phenylenediamine
      (SALOPHEN) as derivatization reagent. The detection wavelength of ultraviolet was
      226 nm with Hypersil ODS2 C18 column (250 mm*4.6 mm, 5 MU m) as stationary phase,
      and pH 10.0 methanol-water (80:20, v/v) as mobile phase. The linear range of Pb2+
      was 0.1-30 mg/L and the linear correlation coefficient was 0.9988. The limit of
      detection was 0.01 mg/L with the recoveries of 91.87%-96.96%. The method has high
      sensitivity and stability with satisfactory results, which can be used for the
      detection of Pb2+ in tea samples.

PMID- 29048820
TI  - [Method development of reversed-phase preparative liquid chromatography for
      insulin].
AB  - The development and optimization of reversed-phase preparative liquid
      chromatography method for insulin were performed. The chromatographic retention,
      sample loading and peak broadening were investigated. The mobile phase gradient
      conditions and stationary phases were optimized. The parameters of the method
      contained the peak broadening levels under different amounts of sample loading
      and the concentration distribution of the target compound in the elution curves.
      The parameters of peak broadening levels were defined and expressed as a matrix,
      which consisted of sample loading, the forward broadening and the backward
      broadening levels. The most suitable chromatographic system (including stationary
      phases and mobile phase conditions) was selected. A gradient program with slow
      change of the strong elution solvent was used. The most suitable stationary phase
      should exhibit the narrower peak broadening and the peaks were best to broaden to
      both sides comparing to that under the analytical conditions. Besides, the
      concentration distribution of the target compound should be focused on the middle
      of the elution. The guide principles were validation by purification of crude
      insulin products. The preparative chromatographic system constructed through this
      method can remove impurities effectively. The method has good practical value. It
      can provide reference for the development of preparative chromatographic methods
      of other macromolecular compounds.

PMID- 29048821
TI  - [Application of asymmetrical flow field-flow fractionation for size
      characterization of low density lipoprotein in egg yolk plasma].
AB  - Home-made asymmetrical flow field-flow fractionation (AF4) system, online coupled
      with ultraviolet/visible (UV/Vis) detector was employed for the separation and
      size characterization of low density lipoprotein (LDL) in egg yolk plasma. At
      close to natural condition of egg yolk, the effects of cross flow rate, sample
      loading, and type of membrane on the size distribution of LDL were investigated.
      Under the optimal operation conditions, AF4-UV/Vis provides the size distribution
      of LDL. Moreover, the precision of AF4-UV/Vis method proposed in this work for
      the analysis of LDL in egg yolk plasma was evaluated. The intra-day precisions
      were 1.3% and 1.9% (n=7) and the inter-day precisions were 2.4% and 2.3% (n=7)
      for the elution peak height and elution peak area of LDL, respectively. Results
      reveal that AF4-UV/Vis is a useful tool for the separation and size
      characterization of LDL in egg yolk plasma.

PMID- 29048822
TI  - [Determination of pyrethroid pesticides in tea by series two-solid phase
      extraction-columns cleanup and gas chromatography-tandem mass spectrometry].
AB  - A rapid determination method of three pyrethroid pesticides (cyfluthrin,
      cypermethrin and fenvalerate) in tea was developed by series two-solid phase
      extraction-column cleanup and external standard method coupled with gas
      chromatography-tandem mass spectrometry (GC-MS/MS) in 30 min. The pesticide
      residues in tea were extracted with acetonitrile, and cleaned up by Carb/NH2 and
      SLH solid-phase extraction columns. After filtration, the target compounds were
      analyzed by GC-MS and quantified by the external standard method. Under the
      optimized conditions, good linear ranges of 0.05-2.00 mg/kg were obtained. The
      limits of detection varied from 0.3 to 1.0 MU g/kg. The linear correlation
      coefficients were greater than 0.999. At three spiked levels (0.10, 0.50 and 2.00
      mg/L), the average recoveries were determined between 80.6% and 116.3% in the
      four matrices. The inter-day relative standard deviations were between 1.3%
      12.6%, and the intra-day relative standard deviations were between 2.7% and
      12.1%. This method is simple, fast, and has a good reproducibility, which can
      meet the requirements of the rapid detection of pyrethroid pesticides in tea.

PMID- 29048823
TI  - [Analysis of aromatic hydrocarbons in cracking products of jet fuel by
      comprehensive two-dimensional gas chromatography-mass spectrometry].
AB  - As coking precursors, aromatic hydrocarbons have an effect on the cracking
      stability of fuels. A method for identifying and quantitating aromatics in the
      supercritical cracking products of jet fuel was established by comprehensive two
      dimensional gas chromatography coupled with mass spectrometry (GC*GC-MS). The
      effects of main chromatographic conditions such as initial oven temperature and
      modulation period on the separation of supercritical cracking products were
      studied. The method has good separation ability for polycyclic aromatic
      hydrocarbons (PAH) isomers. A total of 27 aromatics, including monocyclic
      aromatic hydrocarbons, bicyclic aromatic hydrocarbons, tricyclic aromatic
      hydrocarbons, tetracyclic aromatic hydrocarbons, etc., were identified based on
      standard mass spectra, the retention times of standards and literature reports.
      Moreover, the corresponding quantitative determination was achieved by external
      standard method of GC*GC-FID. The results showed that the contents of aromatics
      increased with the increase of gas yield. When gas yield reached 22%, the
      bicyclic aromatic hydrocarbons began to produce, and their contents increased
      exponentially with the increase of gas yield. Compared with the traditional GC
      MS, the method has better separation and qualitative ability, and can be applied
      to the separation of complex samples and qualitative and quantitative analyses of
      cracking products.

PMID- 29048824
TI  - [Regularity of effective carbon numbers of alkanes, alcohols and ethers and its
      application to determination without authentic standards by gas chromatography].
AB  - To realize quantitative analysis without authentic standards by gas
      chromatography, a calculation method of effective carbon numbers (ECNs) was
      developed by determining the relative response factors of 66 alkanes, alcohols,
      ethers with GC-FID and studying the relation between ECNs and chemical
      structures. The correlation coefficient of 0.9998 (N=66) was achieved between
      theoretical values and experimental values of ECNs. Fifty-seven percent of
      determined compounds had relative deviations within +/-1% and all of them had
      relative deviations within +/-3%. This method is as accurate as common internal
      standard method while used in the determination of oxygenated chemicals in
      gasoline samples, but with far less time and economical cost. It could be used to
      solve the problem of lacking authentic standards or surrogates.

PMID- 29048825
TI  - [Determination of methylene bisthiocyanate in aquatic products by gas
      chromatography with pulsed-flame photometric detector].
AB  - A novel method was developed for the determination of methylene bisthiocyanate
      (MBT) in aquatic products by gas chromatography with pulsed-flame photometric
      detector (GC-PFPD). The samples were extracted by dichloromethane-n-hexane (1:1,
      v/v), concentrated and cleaned up by neutral-alumina SPE cartridges. The extracts
      were eluted with 8 mL dichloromethane, and blown to dryness by nitrogen at 35C.
      The final extracts were redissolved with a mixture of dichloromethane-n-hexane
      (1:1, v/v), separated by an HP-5MS quartz capillary column (30 m*0.32 mm*0.25 MU
      m) and detected by PFPD with external standard method. Under the optimum
      experimental conditions, the standard curve was linear in the range of 1.0-20.0
      mg/L with correlation coefficient of 0.9971. The limit of detection was 0.1
      mg/kg. Recoveries ranged from 65.6% to 97.6% with RSDs of 6.32%-12.8% (n=7). The
      method has good innovative, advanced and practical values.

PMID- 29048826
TI  - [Rapid screening of acidity regulators in dairy by ion chromatography-high
      resolution mass spectrometry].
AB  - A method for screening of acidity regulators in dairy based on ion chromatography
      high resolution mass spectrometry technology (IC-HRMS) was set up. The dairy
      samples were extracted by KOH (pH 7-8) and Oasis MAX SPE column, and separated by
      a Dionex IonPac AS11-HC column (250 mm*4 mm). All the acidity regulators were
      detected by Orbitrap full scan mode. Taking six organic acids as an example, the
      calibration curves showed good linearities in the range of 0.05-5.00 mg/L, and
      the correlation coefficients (r) were higher than 0.99. By detecting the spiked
      samples, the recoveries were in the range of 74.3%-115.5% with the relative
      standard deviations (RSDs) between 0.64% and 4.81%. Malic acid, citric acid,
      lactic acid, succinic acid and adipic acid could be detected by IC-HRMS in the
      commercial dairy samples. The results indicate that the method is simple, rapid
      and suitable for the qualitative screening of acidity regulators in dairy
      products.

PMID- 29048827
TI  - [Simultaneous determination of 11 mycotoxins in feeds by high performance liquid
      chromatography-tandem mass spectrometry].
AB  - A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      method was developed for the simultaneous determination of 11 mycotoxins in
      feeds. The samples were extracted with acetonitrile, then cleaned up by
      multifunctional purification column filler and PRIME HLB solid phase extraction
      column. The 11 mycotoxins were separated on an Agilent Zorbax SB-C18 column (150
      mm*2.1 mm, 3.5 MU m) with gradient elution program, and methanol-5 mmol/L
      ammonium acetate solution containing 0.1%(v/v) formic acid were used as mobile
      phases. The target compounds were detected under electrospray ionization (ESI)
      both in positive and negative modes with multiple reaction monitoring mode, and
      quantified by internal standard method. The results indicated that the 11
      mycotoxins showed good linear relationships in their respective linear ranges,
      and the correlation coefficients were greater than 0.99. The limits of
      quantification (LOQs) were between 2.0 and 50.0 MU g/kg. The average recoveries
      were between 79.3% and 101.6% at three spiked levels (1, 2 and 5 times LOQs) with
      relative standard deviations (RSDs) of 5.9%-13.2% (n=5). The method is simple,
      rapid, sensitive, and can be used for the analysis of the 11 mycotoxins in feeds.

PMID- 29048828
TI  - [A highly sensitive high performance liquid chromatography-electrochemical
      detection method for the determination of five phenolic compounds from Salvia
      miltiorrhiza].
AB  - The determination of antioxidants continues to be interested, since the oxidative
      damage is thought to be one of the main mechanisms involved in nearly all chronic
      renal pathologies. A highly sensitive high performance liquid chromatography
      electrochemical detection (HPLC-ECD) method was developed for evaluating the
      antioxidant properties of Salvia miltiorrhiza (Dan Shen). The method was
      optimized with respect to selectivity and sensitivity. Chromatographic
      conditions, including mobile phase pH value, buffer concentration, buffer type,
      organic solvent type, gradient profile and flow rate, were systematically
      investigated. Low pH value (2.8), low buffer concentration (20 mmol/L NaH2PO4), a
      shallow water-acetonitrile gradient, and a flow rate of 0.2 mL/min were the
      determined optimal conditions for the quantitative analysis of aimed five
      antioxidants from 14 batches of Dan Shen samples. The described method provided a
      good recovery (>95%), a very wide linear range (up to 104 for all analytes), a
      good precision (RSDs<4.01%), and a high sensitivity (LOQ of caffeic acid, 1.5 MU
      g/L). Compared with UV detection, the described ECD method was also more
      effective for evaluating the antioxidant properties of Dan Shen, as it provided
      highly selective detection of electro-active antioxidants.

PMID- 29048829
TI  - [Rapid determination of spirotetramat and its metabolite residues in milk by
      ultra performance liquid chromatography-tandem mass spectrometry].
AB  - A method for the rapid and simultaneous determination of spirotetramat (BYI08330)
      and its four metabolites in milk was developed with ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS). The samples were extracted
      with acetonitrile for precipitating proteins, degreased with hexane, and analyzed
      by UPLC-MS/MS in positive electrospray ionization and multiple reaction
      monitoring (MRM) mode. Good linear relationships between peak areas and mass
      concentrations of the analytes were obtained in the range of 0.5-50 MU g/L with
      correlation coefficients greater than 0.998 (n=6). The limits of detection (LODs,
      S/N=3) and limits of quantification (LOQs, S/N=10) were 0.05-0.30 MU g/L and 0.17
      1.00 MU g/L, respectively. The recoveries at the spiked levels of 1.0, 2.0 and 10
      MU g/L were in the range of 80.0%-108.8% with relative standard deviations (RSDs)
      of 4.8%-15.2% (n=6). The method is fast, sensitive and accurate, and can be used
      to simultaneously determine BYI08330 and its four metabolites in milk.

PMID- 29048830
TI  - [Application of off-line two dimensional reversed-phase liquid
      chromatography/supercritical fluid chromatography to the separation of the seeds
      of Trichosanthes kirilowii Maxim].
AB  - An off-line two dimensional reversed-phase liquid chromatography/supercritical
      fluid chromatography (2D RPLC/SFC) method was developed for the separation of the
      seeds of Trichosanthes kirilowii Maxim. (T. kirilowii.). In the experiment, RPLC
      was used in the first dimension to analyze the samples. And 12 fractions (F1-F12)
      were obtained according to the chromatographic peak collection mode, the
      fractions were re-analyzed in both RPLC and SFC modes. The results clearly showed
      that this 2D method had good orthogonality. The SFC was used as the second
      dimension. Ethanol-n-hexane (3:7, v/v) was used as a modifier in SFC. The
      modifier could provide appropriate elution power. When the sample load increased,
      it could also ensure the solubility of samples. The 2D RPLC/SFC method had
      obvious advantages for separating the compounds with similar properties,
      enriching and purifying the trace components. Finally, 150 peaks could be
      detected. The off-line 2D RPLC/SFC method will be further enlarged to a
      preparative level for preparation of compounds. The method can provide a
      practical reference for the purification of chemical constituents and material
      basis research of the seeds of T. kirilowii. in the future.

PMID- 29048831
TI  - [Fabrication of acylsemicarbazide-based porous organic polymer for selective
      enrichment of glycopeptides].
AB  - An acylsemicarbazide-based porous organic polymer (POP) was facilely prepared by
      the polymerization of benzene-1,3,5-tricarbohydrazide (BTZ) and 1,4-phenylene
      diisocyanate (PDI). The physical properties of as-synthesized material were
      characterized by Fourier-transform infrared spectroscopy (FT-IR), solid-state
      cross polarisation magic angle spinning carbon-13 nuclear magnetic resonance (CP
      MAS 13C NMR), nitrogen adsorption/desorption measurement, water contact angle and
      so on. The specific surface area was 166 m2/g, and the water contact angle was
      46.4 degrees , exhibiting hydrophilic property of the porous material. Thus, POP
      1 was tried to be used for glycopeptides enrichment from tryptic digest of
      standard protein and complex biosamples in hydrophilic mode. The 19 typical N
      linked glycopeptides were identified from 500 fmol tryptic digest of
      immunoglobulin G (IgG) from human serum by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, meanwhile,
      1919 unique glycopeptides with 1350 N-glycosylation sites from 605 different N
      linked glycoproteins were identified from 100 MU g mouse liver tryptic digest by
      capillary liquid chromatography (cLC)-MS/MS analysis. These results demonstrated
      the great potential of POP-1 for glycoproteome analysis.

PMID- 29048832
TI  - [Preparation of cysteine-click maltose modified silica as a hydrophilic
      interaction liquid chromatography material for the enrichment of glycopeptides].
AB  - Because of the low abundance of glycoprotein and glycopeptide in complex
      biological samples, it is urgent to develop an efficient method for glycopeptide
      enrichment in comprehensive and in-depth glycoproteomes research. Herein, a novel
      hydrophilic silica was developed through surface modification with cysteine-click
      maltose (Cys-Mal@SiO2). The developed hydrophilic silica was packed into a solid
      phase extraction (SPE) column, and applied to the highly selective enrichment and
      identification of N-linked glycopeptides. The Cys-Mal@SiO2 demonstrated better
      identification capability over Cys@SiO2, Mal@SiO2 and commercial hydrophilic
      interaction liquid chromatography (HILIC) in glycopeptide enrichment due to the
      synergistic effect of the two kinds of hydrophilic molecules. In the selective
      enrichment of tryptic digest from human immunoglobulin G, glycopeptides with
      higher signal-to-noises were detected by Cys-Mal@SiO2. In addition, 1551 unique
      glycopeptides with 906 N-glycosylation sites from 466 different N-linked
      glycoproteins were identified from the proteins extracted from mouse liver after
      the enrichment with Cys-Mal@SiO2. In contrast, the numbers of identified
      glycopeptides, glycoproteins and N-glycosylation sites identified by Cys@SiO2
      were 211, 67, 127 respectively less than by Cys-Mal@SiO2, and the corresponding
      numbers were 289, 76, 193 by Mal@SiO2. These results showed that the developed
      Cys-Mal@SiO2 is a promising affinity material for N-glycoproteomics research of
      real complex biological samples.

PMID- 29048833
TI  - [New C2 symmetric chiral stationary phases based on L-proline derivatives as
      chains].
AB  - C2 symmetric chiral compounds overlap themselves when rotating with an axis of
      180 degrees  with an axis and have important applications in chiral catalysis and
      chiral separation fields. A novel C2 symmetric stationary phase based on phenyl
      substituted L-proline derivatives was prepared and compared with the similar
      stationary phase based on mono-substituted brush-type stationary phase. The C2
      symmetric stationary phase showed higher enantiodiscrimination capability than
      the mono-substituted stationary phase for 31 acidic, neutral and alkaline
      analytes. The influence of the substitution groups on the terminal phenyl moiety
      on enantioselectivity was investigated. In summary, the best separation
      capability was achieved by the stationary phase with none substitution on the
      endmost phenyl ring. An unusual thermodynamic behavior of the enantioseparation
      property was observed on the C2 symmetric stationary phase for some analytes,
      which showed the different separation mechanism comparing with the corresponding
      mono-substituted stationary phase. The appearance of this novel chiral stationary
      phase has an important significance in enriching the type of brush-type
      stationary phases and widening their applications.

PMID- 29048834
TI  - [Preparation and performance characterization of gold nanoparticles modified
      chiral capillary electrochromatography stationary phase].
AB  - Gold nanoparticles (GNPs, 15 nm) were prepared and introduced to amino groups
      derived silica monolithic column. Bovine serum albumin (BSA) was immobilized via
      covalent modification method onto the carboxylic functionalized GNPs to afford
      chiral stationary phase (CSP) for enantioseparation. GNPs were well dispersed and
      successfully incorporated onto the columns with the contents as high as 17.18% by
      characterization method such as transmission electron microscopy (TEM),
      ultraviolet (UV)-visible absorption spectra and scanning electron microscopy
      (SEM). The preparation conditions of the BSA modified CSP were optimized and 10%
      (v/v) 3-aminopropyltriethoxysilane (APTES) and 15 g/L BSA were selected as
      appropriate reaction conditions. The enantioseparation performance of the BSA
      modified CSP has been investigated by capillary electrochromatography (CEC).
      Enantiomers of tryptophan, ephedrine and atenolol were resolved, and the baseline
      separation of tryptophan was achieved. Meanwhile, the influences of pH value,
      buffer concentrations and applied voltages used on the chiral separation were
      studied, and the optimal separation conditions were 10 mmol/L phosphate buffer at
      pH 7.4 and 15 kV applied voltages. In comparison with the BSA modified CSP
      prepared by physical adsorption, the CSP prepared by covalent modification method
      had better separation results, and the analytes could be separated directly
      without pre-column derivatization. In addition, the prepared BSA modified CSP
      exhibited good run to run repeatability with relative standard deviations (RSDs)
      of the migration times and selectivity factors not more than 2.3% and 0.96%,
      respectively. This work offers a good thinking for modification with other
      proteins or other types of chiral selectors.

PMID- 29048835
TI  - [Determination of pyriminobac-methyl and bispyribac-sodium residues in rice by
      liquid chromatography-tandem mass spectrometry based on QuEChERS].
AB  - A method was developed for the determination of pyriminobac-methyl and bispyribac
      sodium residues in rice by liquid chromatography-tandem mass spectrometry (LC
      MS/MS) coupled with modified QuEChERS. The samples were extracted with acidified
      acetonitrile, and then purified by octadecylsilane bonded silica (C18)
      adsorbents. The analytes were separated on a ZORBAX SB C18 column through a
      gradient elution using 0.1% (v/v) aqueous formic acid aqueous containing 5 mmol/L
      ammonium acetate and acetonitrile as mobile phases. Positive electrospray
      ionization (ESI+) was used. Qualitative work was performed using selected dynamic
      multiple reaction monitoring (dynamic MRM) mode. Quantization was performed using
      external standard method. The results showed good linearities of pyriminobac
      methyl and bispyribac-sodium with correlation coefficients (r2) not less than
      0.996. The limits of detection (LODs) of the method were 0.8 MU g/kg for
      pyriminobac-methyl, and 3 MU g/kg for bispyribac-sodium. The mean spiked
      recoveries of pyriminobac-methyl and bispyribac-sodium at three spiked levels
      were 76.6%-85.6% and 73.0%-86.7%, respectively, and the relative standard
      deviations (RSDs) of pyriminobac-methyl and bispyribac-sodium were 0.9%-3.4% and
      1.2%-5.5%, respectively. This method is simple, rapid, sensitive, and suitable
      for the simultaneous determination of pyriminobac-methyl and bispyribac-sodium in
      rice.

PMID- 29048836
TI  - [Rapid screening the alkaloids of poppy shell in hot pot condiment, beef noodle
      soup and seasoning by direct analysis in real time-tandem mass spectrometry].
AB  - A direct analysis in real time tandem mass spectrometry (DART-MS/MS) method was
      established for quickly screening five illegally added alkaloids of poppy shell
      from the hot pot condiment, beef noodle soup and seasoning. The samples were
      extracted and purified by acetonitrile, and then injected under the conditions of
      ionization temperature of 300C, grid electrode voltage of 150 V and sampling rate
      of 0.8 mm/s using DART in the positive ion mode. The determination was conducted
      by tandem mass spectrometry in positive ESI mode under multiple reaction
      monitoring (MRM) mode. The method is simple and rapid, and can meet the
      requirement of rapid screening and analysis of large quantities of samples.

PMID- 29048837
TI  - [Determination of tristyrylphenol ethoxylates by high performance liquid
      chromatography-tandem mass spectrometry].
AB  - A high performance liquid chromatography-tandem mass spectrometry method for the
      analysis of tristyrylphenol ethoxylates (TSPnEO) was established. The separation
      effects of TSPnEO in the four liquid chromatography modes, including reversed
      phase liquid chromatography column (XBridge C18, 150 mm*2.1 mm, 3.5 MU m),
      hydrophilic interaction liquid chromatography column (XBridge HILIC, 150 mm*2.1
      mm, 3.5 MU m), amide column (XBridge Amide, 150 mm*2.1 mm, 3.5 MU m) and C18
      column (XBridge C18, 50 mm*2.1 mm, 5 MU m) combined with silica column (Nova-Pak
      Silica, 150 mm*2.1 mm, 4 MU m) were investigated. And the separation effects and
      sensitivity of TSPnEO in four mobile phases, such as 5 mmol/L ammonium acetate
      aqueous solution-acetonitrile, 0.1% (v/v) formic acid aqueous solution
      acetonitrile, water-acetonitrile and water-methanol, and three eluent gradient
      conditions were optimized too. The ionization behavior of TSPnEO in electrospray
      ionization (ESI) was also studied. The results showed that in the ESI positive
      ion mode, the identified adducts were[M+NH4]+, and the distribution
      characterization was in Poisson-like distribution. The separation of TSPnEO (n=5
      18) was achieved via C18 column combined with the silica column and water
      acetonitrile as mobile phases according to the degree of ethoxylation.

PMID- 29048838
TI  - [Simultaneous determination of plasma indole and skatole in pregnant women with
      hepatitis B virus infection by high performance liquid chromatography].
AB  - A high performance liquid chromatographic (HPLC) method with fluorescence
      detection (FD) was established to simultaneously determine plasma indole and
      skatole. Plasma samples were pretreated by liquid-liquid extraction.
      Chromatographic separation was accomplished on a Shim-Pack VP-ODS column (150
      mm*4. 6 mm, 4.6 MU m) using an isocratic mixture of 15 mmol/L sodium dihydrogen
      phosphate solution and methanol (40:60, v/v). The fluorescence excitation and
      emission wavelengths were 274 nm and 340 nm, respectively. The linear ranges were
      2.22-88.89 MU g/L for indole and 1.11-44.44 MU g/L for skatole. The detection
      limits were 0.11 MU g/L and 0.06 MU g/L for indole and skatole, respectively. The
      recoveries were in the range of 95.5%-112.3% with the relative standard
      deviations less than 6.8%. The method was successfully applied to the analysis of
      plasma from healthy pregnant women (n=46) and pregnant women with hepatitis B
      virus (HBV) infection (n=29). The results showed that plasma indole and skatole
      levels were significantly different between two groups. In pregnant women with
      HBV infection, the concentrations of indolic compounds were positively associated
      with transaminase levels.

PMID- 29048839
TI  - [Quality evaluation of Yinqiaojiedu tablets by three wavelength fusion
      fingerprint combined with six components quantitative determination and principal
      component analysis].
AB  - The fusion high performance liquid chromatographic fingerprint combined with
      quantification and principal component analysis (PCA) was successfully developed,
      which was applied to assess the quality consistency of 25 Yinqiaojiedu tablets
      (YQJDTs). The resolution index I was employed as an objective function to
      evaluate chromatographic conditions. The chromatographic fingerprints were
      established by reversed-phase high performance liquid chromatography. The
      wavelengths were set at 230, 279 and 327 nm, separately. Then, the three
      wavelength fusion fingerprint was developed by the technique of multi-wavelength
      fusion fingerprint. The linearity, precision, repeatability, stability and
      accuracy of the method were proved to meet the fingerprint analysis criteria.
      Subsequently, the systematic quantified fingerprint method was applied for
      integrative quality discrimination of YQJDTs from both qualitative and
      quantitative perspectives. The results showed that the quality of 25 YQJDTs from
      the two manufacturers were completely qualified and well differentiated. The
      contents of six components were determined simultaneously and combined with
      fingerprint analysis. It was used to evaluate the quality of YQJDT from the
      overall and partial points of view. In addition, the PCA of the fusion
      fingerprint data was applied to get the score plot. It can be clearly
      distinguished the 25 YQJDT samples from the two manufacturers. The method
      proposed in this study was comprehensive and reliable, which could be used for a
      valuable reference to scientifically evaluate and effectively control the quality
      of YQJDT.

PMID- 29048840
TI  - [Determination of four polycyclic aromatic hydrocarbons in olive oil by high
      performance liquid chromatography-fluorescent detection].
AB  - A method for the determination of four polycyclic aromatic hydrocarbons (PAHs)
      such as benzo[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene in
      olive oil by high performance liquid chromatography-fluorescent detection (HPLC
      FLD) was developed. The olive oil samples were diluted with isopropanol and
      cleaned-up by a solid phase extraction cartridge with pi-pi specificity. Critical
      isomers were separated by gradient elution with water-acetonitrile on an Agilent
      ZORBAX Eclipse PAH column (100 mm*2.1 mm, 1.8 MU m). The calibration was
      performed by the use of matrix-matched calibration standards. The results showed
      that there were good linear relationships for the four PAHs in the range of 2.4
      40 MU g/L with correlation coefficients of 0.9990-0.9999. The limits of
      quantification (LOQs) ranged from 0.147 to 0.413 MU g/L, and the recoveries of
      the spiked samples ranged from 95.5% to 103.2%. The intra-day and inter-day
      precisions were in the ranges of 0.10%-1.69% and 2.48%-2.93% (n=5), respectively.
      The method has the characteristics of high sensitivity, low detection limit and
      good precision, and is suitable for rapid and accurate quantitative detection of
      the four PAHs in olive oil.

PMID- 29048841
TI  - [Determination of formaldehyde and acetaldehyde in packaging paper by
      dansylhydrazine derivatization-high performance liquid chromatography
      fluorescence detection].
AB  - A high performance liquid chromatography with fluorescence detection (HPLC-FLD)
      method was developed for the simultaneous determination of formaldehyde and
      acetaldehyde in packaging paper by dansylhydrazine (DNSH) derivatization. The
      samples were extracted by derivatization reagent for 30 min, and derived for 24
      h. After purifying treatment with a PSA/C18 cartridge, a Diamonsil(r) C18 column
      (150 mm*4.6 mm, 5 MU m) was used as stationary phase for separation, the mixtures
      of acetic acid aqueous solution (pH 2.55)-acetonitrile were used as mobile phases
      by gradient elution, and the excitation and emission wavelengths were 330 nm and
      484 nm, respectively. The results showed that the recoveries of formaldehyde and
      acetaldehyde spiked in the samples were 81.64%-106.78%, and the relative standard
      deviations (RSDs) were 2.02%-5.53% (n=5). The limits of detection of formaldehyde
      and acetaldehyde were 19.2 MU g/kg and 20.7 MU g/kg, respectively. The limits of
      quantification of formaldehyde and acetaldehyde were 63.9 MU g/kg and 69.1 MU
      g/kg, respectively. The method is simple, sensitive and reproducible. It provides
      a basic approach for the determination of trace formaldehyde and acetaldehyde.

PMID- 29048842
TI  - [Determination of olive oil content in olive blend oil by headspace gas
      chromatography-mass spectrometry].
AB  - A method for the determination of the content of olive oil in olive blend oil by
      headspace gas chromatography-mass spectrometry (SH-GC/MS) was established. The
      amount of the sample, the heating temperature, the heating time, the amount of
      injection, the injection mode and the chromatographic column were optimized. The
      characteristic compounds of olive oil were found by chemometric method. A sample
      of 1.0 g was placed in a 20 mL headspace flask, and heated at 180C for 2700 s.
      Then, 1.0 mL headspace gas was taken into the instrument. An HP-88
      chromatographic column was used for the separation and the analysis was performed
      by GC/MS. The results showed that the linear range was 0-100%(olive oil content).
      The linear correlation coefficient (r2) was more than 0.995, and the limits of
      detection were 1.26%-2.13%. The deviations of olive oil contents in the olive
      blend oil were from -0.65% to 1.02%, with the relative deviations from -1.3% to
      6.8% and the relative standard deviations from 1.18% to 4.26% (n=6). The method
      is simple, rapid, environment friendly, sensitive and accurate. It is suitable
      for the determination of the content of olive oil in olive blend oil.

PMID- 29048843
TI  - [Analysis of hydrogen isotopes by gas chromatography using a MnCl2 coated gamma
      Al2O3 capillary packed column].
AB  - The conventional packed column gas chromatographic analysis of hydrogen isotopes
      has low column efficiency, broad peak and long retention time. In this work, a
      gamma-Al2O3 with MnCl2 coated capillary packed column was tested at cryogenic
      temperature. The systematic column efficiency analysis and the hydrogen isotopes
      analytical technique research had been carried out. The results showed that, the
      gamma-Al2O3 with MnCl2 coating could greatly improve the surface degree of order,
      pore structure and adsorption properties. Also the o-H2 peak and p-H2 peak were
      eluted in a single area. The gamma-Al2O3 with MnCl2 coating was packed into a
      0.53 mm inner diameter and 1.0 m long fused silica capillary column. It had a
      good linear relationship used this column with thermal conductivity detector
      (TCD) to detect the volume concentrations of hydrogen isotopes from 1 to 10 mL/L,
      and the relative error was less than 5% for low concentration sample testing. For
      H2, HD and D2, the retention times can be shortened to 39, 46 and 60 s,
      respectively. The limits of detection were reduced to 0.046, 0.067 and 0.072
      mL/L, respectively. Compared with conventional packed column, capillary packed
      column had sharper peak form, higher separation degree of adjacent components,
      shorter retention time and lower detection limits. The above results indicate
      that the capillary packed column with TCD detector can be used for fast detection
      of low concentration of hydrogen isotopes and their online analysis.

PMID- 29048844
TI  - [Determination of microcystins in algal bloom samples by ultra performance liquid
      chromatography-tandem mass spectrometry and elimination of their matrix effects].
AB  - A rapid and simple method was commonly used for the determination of microcystins
      by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
      The reliability, accuracy and sensitivity of LC-MS/MS determination were affected
      by the matrix effect because of the complex matrices in algal bloom samples. In
      this study, the matrix interference and matrix effect problems were effectively
      reduced or eliminated by diluting samples, optimizing gradient elution programs,
      and reducing injection volumes. The correlation coefficients (r2) of the seven
      microcystins were >= 0.99. The limits of detection and limits of quantification
      ranged from 0.064 MU g/L to 0.103 MU g/L and 0.213 MU g/L to 0.343 MU g/L,
      respectively. Algal bloom samples were determined by diluting 10 times and
      injecting 5 MU L of sample volume. The method provides some references for the
      determination of microcystins. It is of great significance for ensuring the
      safety of drinking water source.

PMID- 29048845
TI  - [Determination of 20 pyrethroid residues in vegetable foods by gas chromatography
      tandem mass spectrometry].
AB  - A method of gas chromatography-tandem mass spectrometry (GC-MS/MS) was developed
      for the simultaneous determination of 20 pyrethroid residues in vegetable foods.
      The samples were extracted by acetone-n-hexane (1:1, v/v), cleaned up by
      activated charcoal column and quantified by external standard method. The
      correlation coefficients (r2) of all the 20 pyrethroid pesticides in the range of
      0.005-1.0 mg/L were not less than 0.990. The limits of detection (LODs) were 2.0
      MU g/kg when signal/noise (S/N) > 3. The limits of quantification (LOQs) were 5.0
      MU g/kg (S/N > 10). For recovery test, there were three levels (low, medium and
      high) spiked in 11 matrices. The average recoveries of the method were 75.2%-107%
      and the relative standard deviations (RSDs, n=6) were 3.08%-12.1%. The results
      demonstrated that the method is simple and has specific pretreatment steps. The
      method is suitable for the screening and confirmation of the 20 pyrethroid
      pesticides in vegetable foods.

PMID- 29048846
TI  - [A novel ship-borne positive pressure solid phase extraction device to enrich
      organo chlorinated and pyrethroid pesticides in seawater].
AB  - A novel solid phase extraction (SPE) device driven by positive pressure was
      developed instead of negative pressure from a vacuum pump, in order to enrich
      organo chlorinated and pyrethroid pesticides in seawater. The water sampling
      bottles and the pipelines which touch water samples were made of plastic material
      without chlorine. In order to ensure the sealing and firmness, the whole device
      were tightened with nut and bolt. The inner pressure (0.1-0.3 MPa) in the water
      sampling bottle was provided by the small air pump (powered by 12 V cell)
      controlled by a microprogrammed control unit (MCU) and pressure sensor to keep
      the water flow rate (4.0-6.0 mL/min). The pre-conditioned SPE column can be used
      for the enrichment of pesticides within four weeks, and the loaded SPE column can
      be eluted for detection within six weeks with recoveries greater than 80%. The
      linearity of the method was good with the correlation coefficient more than 0.9.
      The limits of quantification (LOQs) were 0.8-6 ng/L. The recoveries of the
      pesticides at three spiked levels (3 parallel samples) were 86.1%-95.5% with the
      relative standard deviations less than 10%. The benzene hexachlorides (BHCs) and
      dichloro-diphenyl-trichloroethanes (DDTs) were detected in seawater samples. The
      device has good application in enriching organo chlorinated and pyrethroid
      pesticides in seawater.

PMID- 29048847
TI  - [Preparation of filter paper with chiral separation function by oxidation and
      Schiff-base reaction].
AB  - Paper chromatography (PC) is a highly flexible, fast, and efficient separation
      method. In this study, a chromatographic paper with a chiral separation function
      was investigated and a paper chromatographic method for chiral separation was
      developed. Single-factor experiments and orthogonal tests were used to determine
      the optimal oxidation conditions for filter paper. The optimal conditions were
      that sodium periodate 4% (mass percentage), pH 2 buffer solution, reaction
      temperature 45C, and reaction time 4 h. Under the optimal conditions, the
      aldehyde group content of a dialdehyde-based filter paper was 57.93% (amount of
      substance percentage). A paper-based chiral separation material was synthesized
      by a microwave-assisted Schiff-base reaction of the oxidized filter paper with L
      glutamic acid. The developing solvent for separating racemic tartaric acid using
      this chiral filter paper consisted of 100 mL of n-butanol, 50 mL of 50%(v/v)
      acetic acid, and 0.1000 g of bromophenol blue. The rate of flow (Rf) values of L
      tartaric acid and D-tartaric acid were 0.52 and 0.40, respectively. This method
      does not require large-scale equipment to perform the chiral separation and it is
      therefore suitable for general teaching, research, and industrial applications.

PMID- 29048848
TI  - [Present situation and development trends of asymmetrical flow field-flow
      fractionation].
AB  - Field-flow fractionation (FFF) is a kind of mature separation technologies in the
      field of bioanalysis, feasible of separating analytes with the differences of
      certain physical and chemical properties by the combination effects of two
      orthogonal force fields (flow field and external force field). Asymmetrical flow
      field-flow fractionation (AF4) is a vital subvariant of FFF, which applying a
      vertical flow field as the second dimension force field. The separation in AF4
      opening channel is carried out by any composition carrier fluid, universally and
      effectively used in separation of bioparticles and biopolymers due to the non
      invasivity feature. Herein, bio-analytes are held in bio-friendly environment and
      easily sterilized without using degrading carrier fluid which is conducive to
      maintain natural conformation. In this review, FFF and AF4 principles are briefly
      described, and some classical and emerging applications and developments in the
      bioanalytical fields are concisely introduced and tabled. Also, special focus is
      given to the hyphenation of AF4 with highly specific, sensitive detection
      technologies.

PMID- 29048849
TI  - [Preparation and evaluation of hydrophilic interaction/reversed-phase mixed-mode
      chromatographic packing based on polylsilsesquioxane microspheres].
AB  - Hydrophilic interaction (HILIC)/reversed-phase (RPLC) mixed-mode chromatography
      is widely used in separating both hydrophobic and hydrophilic compounds, but its
      pH range is limited which is harmful to the separation of alkaline drugs.
      Monodispersed and porous cysteine-modified vinyl functionalized
      polymethylsilsesquioxane (C-V-PMSQ) microspheres were prepared by thiol-ene click
      chemistry. Elemental analysis revealed that cysteine was successfully bonded to
      the surface of microspheres. C-V-PMSQ microspheres had excellent monodispersity,
      favorable chemical stability and simple preparation process. The chromatographic
      behavior of C-V-PMSQ stationary phase was investigated by employing several
      nucleosides and nucleic acids under HILIC mode and RPLC mode. Retention factors
      versus volume percentage of aqueous solution exhibited a U-curve, which can be
      evaluated as an indication for HILIC/RPLC mixed-mode behavior of the stationary
      phase. This new stationary phase presented stronger retention behavior when
      employing alkylbenzenes as evaluation system. In addition, a series of
      hydrophilic and hydrophobic compounds were separated at the same time using this
      new stationary phase. Furthermore, baseline separation for the major three active
      components of Chinese herbal medicine Radix Sophorae flavescentis was achieved
      under HILIC and RPLC modes with highly alkaline mobile phase. The excellent
      chemical stability and base deactivated nature make the organosilicas ideal
      stationary phases for the separation of basic compounds. What's more, it even can
      achieve two-dimensional liquid chromatography separation on an HPLC column.

PMID- 29048850
TI  - [Stable isotope labeling and parallel reaction monitoring-based proteomic
      quantification for biomarker screening and validation of hepatocellular
      carcinoma].
AB  - Liver cancer is the fifth most common cancer with extremely low five year
      survival rate. Early diagnosis is of great importance for cancer therapy. In this
      work, stable isotope labeling-based relative quantitative proteomics and parallel
      reaction monitoring-based target proteomics were combined for cancer biomarker
      screening and validation. By using this strategy, 70 significantly changed
      proteins in hepatocellular carcinoma tissues were obtained, among which seven
      proteins were further validated. The validated proteins contain the clinically
      used hepatocellular carcinoma (HCC) biomarker alpha-fetoprotein (AFP) and the
      reported biomarker candidates Heat shock protein HSP 90-beta (HSP90), fatty acid
      binding protein, epidermal (FABP5) and alcohol dehydrogenase 4 (ADH4), which
      demonstrated the robustness of the strategy. The proteins identified in this work
      could be benefit for further HCC biomarker screening and clinical validation.
      Moreover, this strategy could be further applied to other cancer types.

PMID- 29048851
TI  - [Rapid screening of 44 pesticide residues in ginger and scallion by ultra
      performance liquid chromatography coupled with quadrupole-time of flight mass
      spectrometry].
AB  - An analytical method was established for the simultaneous determination of 44
      pesticide residues in ginger and scallion by ultra performance liquid
      chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q
      TOF/MS). The samples were extracted with acetonitrile containing 0.1% (v/v)
      acetic acid aqueous solution, and cleaned-up by primary secondary amine (PSA) and
      octadecyl bonded silica (C18) adsorbents. The compounds were separated on a
      Poroshell 120 SB-C18 column (100 mm*3.0 mm, 2.7 MUm) with 0.1% (v/v) formic acid
      aqueous solution containing 5 mmol/L ammonium acetate-acetonitrile as mobile
      phases under gradient elution. The eluent was determined by UPLC-Q-TOF/MS with
      electrospray ionization in positive mode. The quantification analysis was
      performed with the external standard method. In all ions MS/MS mode, the
      compounds were qualitatively screened and confirmed by one data acquisition. The
      correlation coefficients (r) were greater than 0.995 in the linear ranges of the
      44 pesticides. The limits of quantification (LOQs, S/N=10) of the 44 pesticides
      were 2.5-5.0 MUg/kg. At the three spiked levels, the recoveries were between
      73.4% and 113.7% with the relative standard deviations (RSDs) ranging from 0.7%
      to 12.1% (n=6). The method effectively improves the determination efficiency of
      pesticide residues screening by high-resolution mass spectrometry.

PMID- 29048852
TI  - [Rapid determination of 15 nutrients in rice by ultra high performance liquid
      chromatography-linear ion trap/orbitrap high resolution mass spectrometry].
AB  - A rapid method was developed for the simultaneous determination of 15 nutrients
      containing eight vitamin E, six gamma-oryzanols and beta-carotene in rice by
      ultra high performance liquid chromatography-linear ion trap/orbitrap high
      resolution mass spectrometry (UHPLC-LTQ/Orbitrap HRMS). The analytes were
      extracted by methanol containing 0.05% (v/v) 2,6-di-tert-butyl-4-methylphenol
      (BHT) under the ultrasonic condition, then separated by a Poroshell 120 PFP
      column (150 mm*3.0 mm, 2.7 MUm) with a gradient elution program using 0.1% (v/v)
      formic acid aqueous solution and methanol containing 0.1% (v/v) formic acid as
      mobile phases. The detection was performed using an LTQ/Orbitrap HRMS detector
      with full scan in positive ion mode. Fifteen nutrients were simultaneously
      separated within 13 min. Furthermore, matrix effects of the white and brown rices
      were investigated. The correlation coefficients (r) were >= 0.9950 in the linear
      ranges of the 15 nutrients. The limits of detection (LODs, S/N=3) and limits of
      quantification (LOQs, S/N=10) of the 15 nutrients were 0.2-1.8 MUg/L and 0.7-6.1
      MUg/L, respectively. At the three spiked levels, the recoveries were 73.2%-101.5%
      with the relative standard deviations (RSDs) ranging from 1.1% to 5.0% (n=3). The
      method is accurate, efficient and reliable. It is suitable for the simultaneous
      determination of various nutrients in rice.

PMID- 29048853
TI  - [Rapid screening and identification of food poisonings by ultra high performance
      liquid chromatography coupled with quadrupole-time of flight mass spectrometry].
AB  - A method was developed for the screening and detection of food poisonings by
      ultra high performance liquid chromatography coupled with quadrupole-time of
      flight mass spectrometry (UHPLC-Q-TOF MS). After extracted by acetonitrile and
      cleaned-up by QuEChERS, the extract was separated on a Waters Acquity UPLC BEH
      C18 column (100 mm*2.1 mm, 1.7 MUm) with the gradient elution of 0.1% (v/v)
      formic acid in water and 0.1% (v/v) formic acid in acetonitrile. TOF-MS scan
      information dependent acquisition (IDA)-product ion scan was performed in
      positive electrospray ionization (ESI) mode to acquire high resolution MS and
      MS/MS spectra in one injection, and rapidly screen 581 target compounds by SCIEX
      OS software, including 546 pesticides, 24 mycotoxins, 11 rodenticides. The target
      compounds were qualitatively confirmed by mass accuracy of precursor, isotope
      distribution of precursor, fragment ions of precursor, and library search.
      Carbofuran was detected in 9 out of 11 samples with the proposed method. The
      retention time was further confirmed by the standard of carbofuran. The results
      showed the retention times were coincident between the samples and reference
      standard, and the deviations of accurate mass numbers were all less than 3.7*10
      6. The scope of the relationship was good and the correlation coefficient was
      0.998. The instrumental limit of detection (S/N=3) was 0.3 MUg/kg, and the limit
      of quantification (S/N=10) was 1 MUg/kg. The recoveries at 10, 50, 200 MUg/kg
      levels were 75.6%-95.9%, and the RSDs (n=6) were 3.6%-6.9%. The method is rapid,
      simple, accurate and sensitive. It is suitable for the rapid screening and
      detection of public safety incidents.

PMID- 29048854
TI  - [Determination of the plant growth regulators in batatas by matrix solid-phase
      dispersive extraction and high performance liquid chromatography with tandem mass
      spectrometry].
AB  - An analytical method based on matrix solid-phase dispersive (MSPD) extraction and
      high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was
      established for the determination of forchlorfenuron, 6-benzylaminopurine (6-BA),
      N-(2-ethylhexyl)-5-norbornene-2,3-dicarboximide (MGK 264) and paclobutrazol in
      batatas. The samples were dispersed with silica by grinding, and then extracted
      with methanol. The determination was carried out on a Thermo hypersil GOLD C18
      column (150 mm*2.1 mm, 5 MUm) in gradient elution with mobile phases of methanol
      and ammonium formate (5 mmol/L, containing 0.1% (v/v) formic acid) and detected
      with tandem mass spectrometry using selected reaction monitoring (SRM) mode. The
      quantification was performed using external standard calibration, and the
      calibration curves were performed in the ranges of 10.8-216.0 ng/g
      (forchlorfenuron), 10.8-216.0 ng/g (6-BA), 12.5-250.0 ng/g (MGK 264), 10.2-204.0
      ng/g (paclobutrazol) with the correlation coefficients larger than 0.96. The
      limits of quantification (LOQs) were 0.1-0.3 ng/g. The spiked recoveries at the
      levels of 50, 100 and 200 ng/g of these four plant growth regulators were in the
      range of 85.3%-116.0%, and the relative standard deviations were 0.6%-22.7%. This
      method has advantages of simple operation and good accuracy, and can be used for
      the quantitative determination of forchlorfenuron, 6-BA, MGK 264 and
      paclobutrazol in batatas.

PMID- 29048855
TI  - [Determination of strobilurin fungicides in fruits and their mass fragmentation
      routes by ultra performance liquid chromatography-tandem mass spectrometry].
AB  - A method was developed for the simultaneous determination of six strobilurin
      fungicide (E-metominostrobin, azoxystrobin, kresoxim-methyl, picoxystrobin,
      pyraclostrobin and trifloxystrobin) residues in orange, banana, apple and
      pineapple samples by ultra performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS/MS). The fragmentation routes of all the compounds were
      explained by the aid of a fragment predicting software ACD Lab/MS Fragmenter. The
      samples were extracted by acetonitrile, then cleaned up by amino solid phase
      extraction cartridges (SupelClean LC-NH2). The extracts were separated on a
      ACQUITY UPLC BEH C18 column (50 mm*2.1 mm, 1.7 MUm) with gradient elution.
      Acetonitrile containing 0.1% (v/v) formic acid and 10 mmol/L ammonium acetate
      containing 0.1% (v/v) formic acid were used as mobile phases. The samples were
      detected by electrospray ionization (ESI)-MS/MS in positive ion and multiple
      reaction monitoring (MRM) mode, quantified by external standard method. Good
      linearities were obtained in the range of 5-100 MUg/L (for pyraclostrobin, 1-20
      MUg/L) with correlation coefficients (r2) greater than 0.999. The recoveries
      ranged from 60.4% to 120% with the relative standard deviations between 2.15% and
      15.1% (n=6). The developed method can meet the inspection of the six strobilurin
      residues in the orange, banana, apple and pineapple samples.

PMID- 29048856
TI  - [Rapid determination of four phenolic environmental estrogen residues in cooking
      oil by ultra-performance liquid chromatography-high resolution mass spectrometry
      coupled with solid-phase extraction].
AB  - A fast, sensitive and accurate method for the determination of trace bisphenol S
      (BPS), bisphenol F (BPF), bisphenol A (BPA) and 4-nonylphenol (4-NP) in cooking
      oil samples was developed by ultra-performance liquid chromatography-high
      resolution mass spectrometry (UPLC-HRMS) coupled with solid-phase extraction
      (SPE). Cooking oil samples were extracted by acetonitrile, then the supernatant
      was purified by SLC SPE cartridges. The chromatographic separation was carried
      out on a Waters ACQUITY UPLC HSS T3 column (100 mm*2.1 mm, 1.8 MUm) with a linear
      gradient elution procedure using 0.05% (v/v) triethanolamine aqueous solution and
      methanol as mobile phases. The quantification analysis was operated in a negative
      electrospray ion (ESI-) source mode under the selected ion monitoring (SIM) mode
      with internal standard method. The four target analytes showed good linearity
      with correlation coefficients (r) greater than 0.999. The limits of detection
      (LODs, S/N=3) and limits of quantification (LOQs, S/N=10) were in the ranges of
      0.03-0.11 MUg/kg and 0.10-0.36 MUg/kg, respectively. The recoveries of the four
      target analytes spiked in oil samples were in the range of 86.3%-96.1% at spiked
      levels of 1.0, 10.0 and 80.0 MUg/kg, respectively, while the relative standard
      deviations (RSDs) were in range of 2.2%-8.8% (n=6). No significant matrix
      interference was found in this method. The proposed method is simple and fast. It
      can be applied for the rapid determination of trace BPS, BPF, BPA, and 4-NP in
      cooking oil samples.

PMID- 29048857
TI  - [Identification of the chemical compositionsof Verbena officinalis L. extract by
      high performance liquid chromatography-photodiode array-high resolution mass
      spectrometry].
AB  - To investigate the main chemical compositions of Verbena officinals L. extract, a
      qualitative high performance liquid chromatography-photodiode array-high
      resolution mass spectrometry (HPLC-PDA-HRMS) method was established. The
      structures of the compounds detected were identified by analyzing the
      chromatographic profiles and the corresponding mass spectra obtained by full scan
      and MSn full scan. Twenty one compounds including iridoid glycosides, flavonoids,
      triterpenoids, phenylpropanoids and phenolic diterpenoids were identified, and
      six of them were not reported in other literatures about Verbena officinalis L.
      extract, such as carnosic acid, carnosol, rosmanol, isorosmanol, rosmarinic acid
      and acacetin-7-O-rutinoside. This method is simple, rapid, accurate and
      sensitive. It provides a reliable scientific basis for the identification of the
      authenticity and quality control of Chinese medicinal materials.

PMID- 29048858
TI  - [Simultaneous determination of diminazene aceturate and isometamidium chloride
      residues in cattle tissues by high performance liquid chromatography with solid
      phase extraction].
AB  - A method for the simultaneous determination of trypanocidal diminazene aceturate
      (DIM) and isometamidium chloride (ISM) that containing benzamidine groups in
      cattle tissues was developed by high performance liquid chromatography (HPLC)
      with solid-phase extraction (SPE). The tissue samples were extracted with
      different proportions of water-acetonitrile, then were cleaned up by Oasis WCX
      cartridges. DIM and ISM were separated by HPLC with a Spherisorb CN column (250
      mm*4.6 mm, 5 MUm). Acetonitrile-0.05 mol/L ammonium formate solution (pH 2.4) was
      used as mobile phases with gradient elution. The detection wavelength of UV was
      set at 380 nm. The limits of detection (LODs) and the limits of quantification
      (LOQs) of DIM and ISM in cattle tissues were 0.01 mg/kg and 0.025 mg/kg,
      respectively. The correlation coefficients (r) of DIM and ISM in cattle tissues
      were not less than 0.9993. The average recoveries of DIM and ISM at three spiked
      levels were 82.2%-97.6% with the intra-day relative standard derivations (RSDs)
      of 0.3%-5.2% (n=5) and inter-day RSDs of 1.3%-5.2% (n=15). The method was
      successfully applied to the analysis of DIM and ISM in cattle tissues. The method
      is rapid, sensitive and repeatable for the determination of diminazene aceturate
      and isometamidium chloride in cattle tissues.

PMID- 29048859
TI  - [Supramolecular solvent-based direct extraction for the determination of
      polycyclic aromatic hydrocarbons in water].
AB  - Supramolecular solvent (SUPRAS) is a nano-structured liquid generated from
      amphiphiles through a sequential self-assembly process. It is an efficient and
      excellent solvent for the sample extraction. In this paper, a method to directly
      extract and rapidly analyze polycyclic aromatic hydrocarbons (PAHs) in water
      samples by high performance liquid chromatography-fluorescence detection (HPLC
      FLD) was developed. The composition and amount of SUPRAS were optimized and
      practical samples were tested. It indicated that the combination of
      tetrahydrofuran and 1-octanol was a suitable SUPRAS for the extraction of four
      PAHs with recoveries between 89.08% and 102.47% and relative standard deviations
      (RSDs) from 1.38% to 3.92% (n=5). Results showed a good linearity of four PAHs
      with the correlation coefficients (R2) more than 0.999. The limits of detection
      (LODs) ranged from 1.26 to 9.23 ng/L. The proposed pretreatment method greatly
      reduces the analysis time. And the solvent-less approach is in accordance with
      the development trend of green chemistry and of great application prospects.

PMID- 29048860
TI  - [Determination and prediction for vapor pressures of organophosphate flame
      retardants by gas chromatography].
AB  - Organophosphate flame retardants (OPFRs) are ubiquitous in the environment. To
      better understand and predict their environmental transport and fate, well
      defined physicochemical properties are required. Vapor pressures (P) of 14 OPFRs
      were estimated as a function of temperature (T) by gas chromatography (GC), while
      1,1,1-trichioro-2,2-bis (4-chlorophenyl) ethane (p,p'-DDT) was acted as a
      reference substance. Their log PGC values and internal energies of phase transfer
      (? vapH) ranged from -6.17 to -1.25 and 74.1 kJ/mol to 122 kJ/mol, respectively.
      Substitution pattern and molar volume (VM) were found to be capable of
      influencing log PGC values of the OPFRs. The halogenated alkyl-OPFRs had lower
      log PGC values than aryl-or alkyl-OPFRs. The bigger the molar volume was, the
      smaller the log PGC value was. In addition, a quantitative structure-property
      relationship (QSPR) model of log PGC versus different relative retention times
      (RRTs) was developed with a high cross-validated value (Q2cum) of 0.946,
      indicating a good predictive ability and stability. Therefore, the log PGC values
      of the OPFRs without standard substance can be predicted by using their RRTs on
      different GC columns.

PMID- 29048861
TI  - [Separation and purification of acteoside from Rehmannia glutinosa by combining
      macroporous resin with high-speed countercurrent chromatography].
AB  - Acteoside,a chemical component of the traditional Chinese medicinal herb
      Rehmannia glutinosa,was separated from the plant by a combination of macroporous
      resin column chromatography and high-speed countercurrent chromatography.The
      static adsorption and desorption of acteoside in the crude extract were in
      vestigated using four kinds of macroporous resin,among which the D101 macroporous
      resin presented the best adsorption and desorption rates toward the compound.The
      crude extract was then gradient-eluted with increa-sing volume percentages of
      ethanol,where it was found that the highest content of acteoside was obtained
      when using 10%(v/v) ethanol eluent,in which the purity of acteoside was increased
      from 4.9% to 32.6%.Then,the partially purified crude extract (165 mg) was further
      purified by high-speed countercurrent chroma-tography using a two-phase solvent
      system consisting of ethyl acetate-n-butanol-water (1:4:5,v/v/v),yielding 45 mg
      of acteoside with 96% purity.

PMID- 29048862
TI  - Order Without Intellectual Property Law: Open Science in Influenza.
AB  - Today, intellectual property (IP) scholars accept that IP as an approach to
      information production has serious limits. But what lies beyond IP? A new
      literature on "intellectual production without IP" (or "IP without IP") has
      emerged to explore this question, but its examples and explanations have yet to
      convince skeptics. This Article reorients this new literature via a study of a
      hard case: a global influenza virus-sharing network that has for decades produced
      critically important information goods, at significant expense, and in a loose
      knit group--all without recourse to IP. I analyze the Network as an example of
      "open science," a mode of information production that differs strikingly from
      conventional IP, and yet that successfully produces important scientific goods in
      response to social need. The theory and example developed here refute the most
      powerful criticisms of the emerging "IP without IP" literature, and provide a
      stronger foundation for this important new field. Even where capital costs are
      high, creation without IP can be reasonably effective in social terms, if it can
      link sources of funding to reputational and evaluative feedback loops like those
      that characterize open science. It can also be sustained over time, even by loose
      knit groups and where the stakes are high, because organizations and other forms
      of law can help to stabilize cooperation. I also show that contract law is well
      suited to modes of information production that rely upon a "supply side" rather
      than "demand side" model. In its most important instances, "order without IP" is
      not order without governance, nor order without law. Recognizing this can help us
      better ground this new field, and better study and support forms of knowledge
      production that deserve our attention, and that sometimes sustain our very lives.

PMID- 29048864
TI  - Patient-centred communication in British, Italian and Spanish 'Ask-the
      Expert'healthcare websites.
AB  - Existing studies on the online asynchronous consultationmode afforded by 'Ask-the
      Expert' health websites(e.g. Thomson et al. 2012) are concerned withthe possible
      loss in the quality of interaction betweenpatients and clinicians in this type of
      consultation.The potential loss is worrying, given the central roleof patient
      centred communication (PCC), particularlyempathy, in medical consultation
      practice andpatients' increasing use of and reliance on onlineconsultations. This
      study addresses the followingthree related questions: (1) To what extent is
      PCCrepresented in 'Ask-the-Expert' healthcare websites?(2) Are there noticeable
      differences in PCC betweensites operating in different linguistic and
      culturalsettings (the UK, Spain and Italy)? (3) What are theimplications of the
      above? Seventy exchanges fromthe leading independent health websites
      NetDoctor(UK), Netdoctor (Spain) and Medicitalia (Italy)were analysed, adapting a
      framework developed forthe linguistic analysis of clinical empathy
      (combiningdiscourse analytical and pragmatic categories -Pounds 2011) and drawing
      on existing definitions ofPCC and classifications of advice-giving structures.The
      analysis shows that PCC is used on these sites tovarying degrees, conforming to
      the site's affordances.The significance of the findings and potential
      furtherapplications of the analytical framework are discussedin the final part.

PMID- 29048865
TI  - Counseling and new media technologies: A comparison of problem presentationsin e
      mail and in chat.
AB  - In this article, we examine problem presentations ine-mail and chat counseling.
      Previous studies of onlinecounseling have found that the medium (e.g., chat,
      email)impacts the unfolding interaction. However, theimplications for counseling
      are unclear. We focus onproblem presentations and use conversation analysisto
      compare 15 chat and 22 e-mail interactions fromthe same counseling program. We
      find that in e-mailcounseling, counselors open up the interactional spaceto
      discuss various issues, whereas in chat, counselorsrestrict problem presentations
      and give the client lessspace to elaborate. We also find that in e-mail
      counseling,clients use narratives to present their problemand orient to its
      seriousness and legitimacy, while inchat counseling, they construct problem
      presentationsusing a symptom or a diagnosis. Furthermore, in emailcounseling,
      clients close their problem presentationsstating completeness, while in chat
      counseling,counselors treat clients' problem presentations as incomplete.Our
      findings shed light on how the mediumhas implications for counseling.

PMID- 29048866
TI  - 'The words are stuck inside me; I write to heal': Memory, recall, and repetition
      inPTSD blogs.
AB  - This paper addresses issues around the automaticrepetition of particular memories
      in the narratives/ blog accounts of individuals with Post TraumaticStress
      Disorder (PTSD). Based on a long-term projectthat examines how people with
      various body-relatedconditions and ailments write or speak abouttheir bodies, the
      focus of this paper is on 80 blog accountswherein individuals with PTSD write
      bothabout living with the condition and about their stepstowards healing
      themselves. The paper pays specialattention to how the act of repeated blogging
      countersthe paralyzing repetition in their heads, leadingthem to re-cognize
      particular distressing life-eventsand thus creating alternate episodic structures
      (Gee1992). In particular, the article addresses: What insightsabout repetition
      and memory are we able toglean from PTSD pathographies, and in what waysdoes
      current scholarship in narrative analysis, appliedsociolinguistics, and
      psychology permit a morecomplex understanding of the condition?

PMID- 29048867
TI  - 'I cant bear the thought that he might not recognise me': Personal narratives as
      asite of identity work in the online Alzheimer's support group.
AB  - Narrative of personal experience, as a subjective interpretationof a set of
      events, constitutes a particularlyfertile site for the construction of identity.
      It enablesthe teller to voice and (re-)organize disruptivephenomenological
      experiences, socialize emotions orforge interpersonal relations. Consequently,
      the narratoris able to access various facets of their identityand 'bring
      multiple, partial selves to life' (Ochs and Capps 1996: 19).Informed by the
      methods and insights of computer-mediated discourse analysis,
      conversationanalysis and membership categorization analysis,and positioning
      narrative as a situated practicewithin social interaction, this paper scrutinizes
      publiclyaccessible data (15 forum threads) nested withina UK-based online
      Alzheimer's support group todemonstrate how Alzheimer's patients' family
      caregiversco-construct their sense of self when disclosingmorally delicate
      aspects of their identities. Theanalysis demonstrates that the discursive space
      ofthe online support group encourages caregivers todisclose disruptions of
      predicates and activities associatedwith the 'family' membership
      categorizationdevice. It also shows that the medium-affordedmode of engagement
      enables caregivers to graduallyincorporate their unveiled aversive experiences
      intotheir autobiographical flow, with the help of otherparticipants' responses
      which normalize these categorydisruptions.

PMID- 29048868
TI  - Control of Carbon Nanotube Solvatochromic Response to Chemotherapeutic Agents.
AB  - Alkylating agents such as cisplatin play an essential role in chemotherapy
      regimens, but initial and acquired resistance in many cancer types often dampen
      therapeutic response. The poor understanding of the mechanisms of resistance
      highlight the need for quantitative measurements of alkylating agent distribution
      at both the tissue and subcellular levels. Sensors for use in live animals and
      cells would allow for more effective study of drug action and resistance. Toward
      this end, single-walled carbon nanotubes suspended with single-stranded DNA have
      suitable optical properties for in vivo sensors, such as near-infrared emission
      and sensitivity to the local environment via solvatochromic responses. Currently,
      solvatochromic changes of such sensors have been limited by the chemical nature
      of the analyte, making it impossible to control the direction of energy emission
      changes. Here, we describe a new approach to control the direction and magnitude
      of solvatochromic responses of carbon nanotubes. We found that the alkylation of
      DNA on the nanotube surface can result in small changes in DNA conformation that
      allow the adsorption of amphiphiles to produce large differences (>14 nm) in
      response to different drugs. The technique surprisingly revealed differences
      among drugs upon alkylation. The ability to control carbon nanotube
      solvatochromism as desired may potentially expand the application of nanotube
      based optical sensors for new classes of analytes.

PMID- 29048869
TI  - Novel ZIF-300 Mixed-Matrix Membranes for Efficient CO2 Capture.
AB  - Because of the high separation performance and easy preparation, mixed-matrix
      membranes (MMMs) consisting of metal-organic frameworks have received much
      attention. In this article, we report a novel ZIF-300/PEBA MMM consisting of
      zeolite imidazolate framework (ZIF-300) crystals and polyether block amide (PEBA)
      matrix. The ZIF-300 crystal size was effectively reduced by optimizing the
      hydrothermal reaction condition from ~15 to ~1 MUm. The morphology and
      physicochemical and sorption properties of the synthesized ZIF-300 crystals and
      as-prepared ZIF-300/PEBA MMMs were systematically studied. The results showed
      that ZIF-300 crystals with a size of ~1 MUm maintained excellent preferential CO2
      sorption over N2 without degradation of the crystal structure in the MMMs. As a
      result, uniformly incorporated ZIF-300 crystals highly enhanced both the CO2
      permeability and the CO2/N2 selectivity of pure PEBA membrane. The optimized ZIF
      300-PEBA MMMs with a ZIF-300 loading of 30 wt % exhibited a high and stable CO2
      permeability of 83 Barrer and CO2/N2 selectivity of 84, which are 59.2% and 53.5%
      higher than pure PEBA membrane, respectively. The obtained performance surpassed
      the upper bound of state-of-the-art membranes for CO2/N2 separation. This work
      demonstrated that the proposed ZIF-300/PEBA MMM could be a potential candidate
      for an efficient CO2 capture process.

PMID- 29048870
TI  - Daptomycin Pore Formation Is Restricted by Lipid Acyl Chain Composition.
AB  - Daptomycin is a calcium-dependent lipopeptide antibiotic that is used clinically
      against various Gram-positive pathogens. It acts on bacterial cell membranes,
      whose susceptibility varies with the content of phosphatidylglycerol (PG). Some
      studies have reported that daptomycin permeabilizes and depolarizes bacterial
      cell membranes, while others have found no evidence of membrane permeabilization
      and thus proposed different mechanisms of antibacterial action. Divergent
      observations have also been reported regarding the effect of daptomycin on model
      membranes, which were found to be permeabilized nonselectively, selectively for
      small cations, or not at all. While these diverging model studies did consider
      the functional roles of different lipid head groups, they assumed that the acyl
      chains were interchangeable. We here show this assumption to be erroneous. In
      equimolar mixtures of PG and phosphatidylcholine (PC), dimyristoyl lipids support
      membrane permeabilization, whereas dioleyl and palmitoleyl lipids do not, even
      though daptomycin does bind to and form oligomers on all of these membranes.
      These observations help reconcile some of the discrepant findings in the
      literature.

PMID- 29048871
TI  - Sensitive and Specific Detection of l-Lactate Using an AIE-Active Fluorophore.
AB  - l-Lactate is a vital biomarker for many diseases and physiological fatigue. An
      AIE-active fluorophore (TPE-HPro) is combined with l-lactate oxidase (LOx) to
      determine l-lactate in aqueous fluid. The assay shows excellent sensitivity and
      anti-interference performance with a limit of detection (LOD) of 5.5 MUM. In
      addition, sensitive detection of l-lactate is achieved even in a protein-rich
      environment. It is proposed that quantification of l-lactate be performed at 20
      or 60 min in the current method. These characteristics endow the fluorometric
      assay with great potential for biomedical diagnostics.

PMID- 29048872
TI  - High Rate Performing in Situ Nitrogen Enriched Spherical Carbon Particles for
      Li/Na-Ion Cells.
AB  - Nitrogen rich, porous spherical carbon particle with the large surface area was
      synthesized by simple pyrolysis of the amorphous covalent organic framework. The
      obtained mesoporous spherical carbon particles with dilated interlayer distance
      (0.377 nm), large surface area (390 m2 g-1) and high level nitrogen doping
      (10.9%) offer eminent electrochemical performance as an anode for both lithium
      ion (LIBs) and sodium ion batteries (SIBs). In LIB applications, the synthesized
      material delivers an average reversible capacity of 820 mAh g-1 after 100 cycles
      at 0.1 A g-1, superior rate capability of 410 and 305 mAh g-1 at 4.0 and 8.0 A g
      1 respectively. In SIBs, the material shows the stable reversible capacity of
      about 238 mAh g-1 for the studied 500 cycles at 0.5 A g-1. The rate and steady
      state cycling performance at high current densities are impressive, being as high
      as 165 mAh g-1 even after 250 cycles at 2.0 A g-1.

PMID- 29048874
TI  - Engineering Nanodisc Scaffold Proteins for Native Mass Spectrometry.
AB  - Lipoprotein nanodiscs are ideally suited for native mass spectrometry because
      they provide a relatively monodisperse nanoscale lipid bilayer environment for
      delivering membrane proteins into the gas phase. However, native mass
      spectrometry of nanodiscs produces complex spectra that can be challenging to
      assign unambiguously. To simplify interpretation of nanodisc spectra, we
      engineered a series of mutant membrane scaffold proteins (MSP) that do not affect
      nanodisc formation but shift the masses of nanodiscs in a controllable way,
      eliminating isobaric interference from the lipids. Moreover, by mixing two
      different belts before assembly, the stoichiometry of MSP is encoded in the peak
      shape, which allows the stoichiometry to be assigned unambiguously from a single
      spectrum. Finally, we demonstrate the use of mixed belt nanodiscs with embedded
      membrane proteins to confirm the dissociation of MSP prior to desolvation.

PMID- 29048873
TI  - Insights into Interactions of Mycobacteria with the Host Innate Immune System
      from a Novel Array of Synthetic Mycobacterial Glycans.
AB  - An array of homogeneous glycans representing all the major carbohydrate
      structures present in the cell wall of the human pathogen Mycobacterium
      tuberculosis and other mycobacteria has been probed with a panel of glycan
      binding receptors expressed on cells of the mammalian innate immune system. The
      results provide an overview of interactions between mycobacterial glycans and
      receptors that mediate uptake and survival in macrophages, dendritic cells, and
      sinusoidal endothelial cells. A subset of the wide variety of glycan structures
      present on mycobacterial surfaces interact with cells of the innate immune system
      through the receptors tested. Endocytic receptors, including the mannose
      receptor, DC-SIGN, langerin, and DC-SIGNR (L-SIGN), interact predominantly with
      mannose-containing caps found on the mycobacterial polysaccharide
      lipoarabinomannan. Some of these receptors also interact with phosphatidyl-myo
      inositol mannosides and mannose-containing phenolic glycolipids. Many glycans are
      ligands for overlapping sets of receptors, suggesting multiple, redundant routes
      by which mycobacteria can enter cells. Receptors with signaling capability
      interact with two distinct sets of mycobacterial glycans: targets for dectin-2
      overlap with ligands for the mannose-binding endocytic receptors, while mincle
      binds exclusively to trehalose-containing structures such as trehalose
      dimycolate. None of the receptors surveyed bind furanose residues, which often
      form part of the epitopes recognized by antibodies to mycobacteria. Thus, the
      innate and adaptive immune systems can target different sets of mycobacterial
      glycans. This array, the first of its kind, represents an important new tool for
      probing, at a molecular level, biological roles of a broad range of mycobacterial
      glycans, a task that has not previously been possible.

PMID- 29048875
TI  - Exploring Chemistry in Microcompartments Using Guided Droplet Collisions in a
      Branched Quadrupole Trap Coupled to a Single Droplet, Paper Spray Mass
      Spectrometer.
AB  - Recent studies suggest that reactions in aqueous microcompartments can occur at
      significantly different rates than those in the bulk. Most studies have used
      electrospray to generate a polydisperse source of highly charged microdroplets,
      leading to multiple confounding factors potentially influencing reaction rates
      (e.g., evaporation, charge, and size). Thus, the underlying mechanism for the
      observed enhancement remains unclear. We present a new type of electrodynamic
      balance-the branched quadrupole trap (BQT)-which can be used to study reactions
      in microdroplets in a controlled environment. The BQT allows for condensed phase
      chemical reactions to be initiated by colliding droplets with different reactants
      and levitating the merged droplet indefinitely. The performance of the BQT is
      characterized in several ways. Sub-millisecond mixing times as fast as ~400 MUs
      are measured for low velocity (~0.1 m/s) collisions of droplets with <40 MUm
      diameters. The reaction of o-phthalaldehyde (OPA) with alanine in the presence of
      dithiolthreitol is measured using both fluorescence spectroscopy and single
      droplet paper spray mass spectrometry. The bimolecular rate constant for reaction
      of alanine with OPA is found to be 84 +/- 10 and 67 +/- 6 M-1 s-1 in a 30 MUm
      radius droplet and bulk solution, respectively, which demonstrates that
      bimolecular reaction rate coefficients can be quantified using merged
      microdroplets and that merged droplets can be used to study rate enhancements due
      to compartmentalization. Products of the reaction of OPA with alanine are
      detected in single droplets using paper spray mass spectrometry. We demonstrate
      that single droplets with <100 pg of analyte can easily be studied using single
      droplet mass spectrometry.

PMID- 29048876
TI  - Microchemical Plant in a Liquid Droplet: Plasmonic Liquid Marble for Sequential
      Reactions and Attomole Detection of Toxin at Microliter Scale.
AB  - Miniaturizing the continuous multistep operations of a factory into a
      microchemical plant offers a safe and cost-effective approach to promote high
      throughput screening in drug development and enforcement of
      industrial/environmental safety. While particle-assembled microdroplets in the
      form of liquid marble are ideal as microchemical plant, these platforms are
      mainly restricted to single-step reactions and limited to ex situ reaction
      monitoring. Herein, we utilize plasmonic liquid marble (PLM), formed by
      encapsulating liquid droplet with Ag nanocubes, to address these issues and
      demonstrate it as an ideal microchemical plant to conduct reaction-and-detection
      sequences on-demand in a nondisruptive manner. Utilizing a two-step azo-dye
      formation as our model reaction, our microchemical plant allows rapid and
      efficient diazotization of nitroaniline to form diazonium nitrobenzene, followed
      by the azo coupling of this intermediate with target aromatic compound to yield
      azo-dye. These molecular events are tracked in situ via SERS measurement through
      the plasmonic shell and further verified with in silico investigation.
      Furthermore, we apply our microchemical plant for ultrasensitive SERS detection
      and quantification of bisphenol A (BPA) with detection limit down to 10 amol,
      which is 50 000-fold lower than the BPA safety limit. Together with the
      protections offered by plasmonic shell against external environments, these
      collective advantages empower PLM as a multifunctional microchemical plant to
      facilitate small-volume testing and optimization of processes relevant in
      industrial and research contexts.

PMID- 29048877
TI  - Stereoselective Synthesis of Benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12
      diones with Two Diversity Positions.
AB  - Herein, we report a stereoselective formation of tetrahydro-6H
      benzo[e][1,4]oxazino[4,3-a][1,4]diazepine-6,12(11H)-diones. Their preparation
      consisted in solid-phase synthesis of linear intermediates starting from polymer
      supported Ser(tBu)-OH. Using various 2-nitrobenzoic acids and bromoketones, the
      key intermediates were obtained in five steps and subjected to trifluoroacetic
      acid-mediated cleavage from the resin, followed by stereoselective reduction with
      triethylsilane. Subsequent catalytic hydrogenation of the nitro group and
      cyclization yielded the target compounds with full retention of the C12a
      stereocenter configuration.

PMID- 29048878
TI  - ATRP Fabricated and Short Chain Polyethylenimine Grafted Redox Sensitive
      Polymeric Nanoparticles for Codelivery of Anticancer Drug and siRNA in Cancer
      Therapy.
AB  - To overcome the limitations of conventional chemotherapy, nanoparticle-mediated
      combinatorial delivery of siRNA and drugs represents a new approach to overcome
      its associated side effects. Designing safe and efficient vehicles for their
      codelivery has emerged as a potential challenge in the clinical translation of
      these formulations. Herein, we have demonstrated a novel "two-in-one" polyplex
      nanosystem developed from redox sensitive, short chain polyethylenimine modified
      poly[(poly(ethylene)glycol methacrylate]-s-s-polycaprolactone copolymer
      synthesized by atom-transfer free-radical polymerization (ATRP), which can
      deliver doxorubicin and polo-like kinase I (plk1) siRNA, simultaneously for an
      enhanced chemotherapeutic effect. The nanoparticles were found to be stable at
      physiological buffer with and without fetal bovine serum (FBS). The developed
      polymeric nanosystem was found to be biocompatible and hemocompatible in vitro
      and in vivo at repeated dose administrations. The polymer could easily self
      assemble into ~100 nm spherical nanoparticles with enhanced doxorubicin loading
      (~18%) and effective siRNA complexation at a polymer to siRNA weight ratio of 15.
      The doxorubicin loaded nanoparticles exhibited ~4-fold higher drug release in
      endosomal pH (pH 5) containing 10 mmol of GSH compared to pH 7.4, depicting their
      redox-sensitive behavior. The polyplexes were capable of delivering both cargos
      simultaneously to cancer cells in vitro as observed by their excellent
      colocalization in the cytoplasm of MDA-MB-231 and HeLa cells using confocal laser
      microscopy. Moreover, in vitro transfection of the cells with polyplexes
      exhibited 50-70% knockdown of plk1-mRNA expression in both cell lines. In vivo
      administration of the drug loaded polyplexes to EAT tumor bearing (EAT, Ehrlich
      ascites tumor) Swiss albino mice showed a ~29-fold decrease in percent tumor
      volume in comparison to the control group. The results highlight the therapeutic
      potential of the polyplexes as a combined delivery of doxorubicin and plk1-siRNA
      in cancer therapy.

PMID- 29048879
TI  - Near-Infrared Fluorescent Probe with Remarkable Large Stokes Shift and Favorable
      Water Solubility for Real-Time Tracking Leucine Aminopeptidase in Living Cells
      and In Vivo.
AB  - Leucine aminopeptidase (LAP) is a kind of proteolytic enzymes and associated
      closely with pathogenesis of cancer and liver injury. Accurate detection of LAP
      activity with high sensitivity and selectivity is imperative to detect its
      distribution and dynamic changes for understanding LAP's function and early
      diagnosing the disease states. However, fluorescent detection of LAP in living
      systems is challenging. To date, rarely fluorescent probes have been reported for
      imaging LAP in vivo. In this study, a novel probe (TMN-Leu) was developed by
      conjugating a near-infrared dicyanoisophorone derivative fluorophore with LAP
      activatable l-leucine amide moiety for the first time. TMN-Leu featured large
      Stokes shift (198 nm), favorable water solubility, ultrasensitive sensitivity
      (detection limit of ~0.38 ng/mL), good specificity, excellent cell membrane
      permeability, low toxicity, and a prominent near-infrared emission (658 nm) in
      response to LAP. TMN-Leu has been successfully applied to track LAP of cancer
      cells and normal cells, monitor LAP changes in different disease models, and
      rapidly evaluate LAP inhibitor in cell-based assay. Notably, this probe firstly
      revealed that HCT116 cells with higher LAP activity were more invasive than LAP
      siRNA transfected HCT116 cells, suggesting that LAP might serve as an indicator
      reflecting the intrinsic invasion ability of cancer cells. Finally, TMN-Leu was
      also employed for in vivo real-time imaging LAP in living tumor-bearing nude mice
      with low background interference. All together, our probe possesses potential
      value as a promising tool for diagnostic application, cell-based screening
      inhibitors and in vivo real-time tracking enzymatic activity in preclinical
      applications.

PMID- 29048880
TI  - Interactions of Native Cyclodextrins with Metal Ions and Inorganic Nanoparticles:
      Fertile Landscape for Chemistry and Materials Science.
AB  - Readily available cyclodextrins (CDs) with an inherent hydrophobic internal
      cavity and hydrophilic external surface are macrocyclic entities that display a
      combination of molecular recognition and complexation properties with vital
      implications for host-guest supramolecular chemistry. While the host-guest
      chemistry of CDs has been widely recognized and led to their exploitation in a
      variety of important functions over the last five decades, these naturally
      occurring macrocyclic systems have emerged only recently as promising macrocyclic
      molecules to fabricate environmentally benign functional nanomaterials. This
      review surveys the development in the field paying special attention to the
      synthesis and emerging uses of various unmodified CD-metal complexes and CD
      inorganic nanoparticle systems and identifies possible future directions. The
      association of a hydrophobic cavity of CDs with metal ions or various inorganic
      nanoparticles is a very appealing strategy for controlling the inorganic subunits
      properties in the very competitive water environment. In this review we provide
      the most prominent examples of unmodified CDs' inclusion complexes with
      organometallic guests and update the research in this field from the past decade.
      We discuss also the coordination flexibility of native CDs to metal ions in CD
      based metal complexes and summarize the progress in the synthesis and
      characterization of CD-metal complexes and their use in catalysis and sensing as
      well as construction of molecular magnets. Then we provide a comprehensive
      overview of emerging applications of native CDs in materials science and
      nanotechnology. Remarkably, in the past few years CDs have appeared as attractive
      building units for the synthesis of carbohydrate metal-organic frameworks (CD
      MOFs) in a combination of alkali-metal cations. The preparation of this new class
      of highly porous materials and their applications in the separation of small
      molecules, the loading of drug molecules, as well as efficient host templates in
      the construction of nanomaterials with the desired functionality, including the
      first-in-class devices including sensors and memristors, are highlighted.
      Finally, CDs as well-known "green" molecular hosts have also been used as ideal
      functional molecules to improve the solubility, stability, and bioavailability of
      inorganic nanoparticles. In this regard, we demonstrate various strategies for
      the preparation of native CDs-modified inorganic nanomaterials such as metal,
      metal oxide, and semiconductor and magnetic nanoparticles, aiming to take
      advantage of both the controlled properties of the inorganic core and the
      controlled properties of the coating molecules. The functionalization of a CD
      hydrophobic cavity with an inorganic nanoparticle is very prospective for the
      development of novel catalytic systems and new tools for highly selective and
      sensitive sensing platforms for various targets.

PMID- 29048881
TI  - Systematic Study of Aluminum Nanoclusters and Anion Adsorbates.
AB  - The interactions between aqueous aluminum (Al) nanoclusters and ions in solution
      influence the reactivity of nanomaterials in natural waters and are crucial to
      the targeted syntheses of aluminum oxides. To contribute to the fundamental
      understanding of how both anion and Al-nanocluster properties affect the
      interactions, we carry out systematic modeling studies that employ density
      functional theory calculations embedded in a continuum solvent model. Energetic
      and electronic structure analysis is applied toward delineating the interactions
      of a range of probe adsorbate anions with Al nanoclusters to elucidate how small
      molecules may react with naturally occurring nanomaterials. The study spans seven
      small molecules on three model Al nanoclusters. Using this ion set, we correlate
      the size, shape, and formal charge of the adsorbate to the trends in adsorption
      energies. A key finding is that the collective effects of exposed oxygen
      functional groups, i.e., the distribution of functional groups, dictates the
      electrostatic potential of the nanocluster surface, which, in turn, controls
      trends in anion adsorption. The computed adsorption and deprotonation trends are
      correlated to known synthetic routes of Al-nanocluster formation and subsequent
      crystallization to give insight into the potential optimization of synthetic
      conditions.

PMID- 29048883
TI  - Charge Transport in Organic Materials: Norm-Conserving Imaginary Time Propagation
      with Local Ionization Energy as the External Potential.
AB  - An additional charge carrier described as its wave function is propagated in
      imaginary time using stepwise matrix multiplication and a correction to ensure
      that the simulation is norm-conserving. The propagation Hamilton operator uses
      the local ionization energy of a rubrene single crystal, calculated with
      semiempirical molecular orbital theory, as an external potential for holes to
      model the interaction with the underlying molecular structure. Virtual electrodes
      are modeled by setting the potentials in the appropriate areas to constant values
      with the difference corresponding to the source-drain voltage. Although imaginary
      time cannot be interpreted directly as time, the simulated gate-dependent
      imaginary transfer rate is in acceptable qualitative agreement with the
      experimentally measured gate-dependent hole-transfer rate through a rubrene
      single crystal.

PMID- 29048882
TI  - Collaborating with Undergraduates To Contribute to Biochemistry Community
      Resources.
AB  - Course-based undergraduate research experiences (CUREs) have gained traction as
      effective ways to expand the impact of undergraduate research while fulfilling
      pedagogical goals. In this Perspective, we present innovative ways to incorporate
      fundamental benefits and principles of CUREs into a classroom environment through
      information/technology-based research projects that lead to student-generated
      contributions to digital community resources (CoRes). These projects represent an
      attractive class of CUREs because they are less resource-intensive than
      laboratory-based CUREs, and the projects align with the expectations of today's
      students to create rapid and publicly accessible contributions to society. We
      provide a detailed discussion of two example types of CoRe projects that can be
      implemented in courses to impact research and education at the chemistry-biology
      interface: bioinformatics annotations and development of educational tools.
      Finally, we present current resources available for faculty interested in
      incorporating CUREs or CoRe projects into their pedagogical practices. In sharing
      these stories and resources, we hope to lower the barrier for widespread adoption
      of CURE and CoRe approaches and generate discussions about how to utilize the
      classroom experience to make a positive impact on our students and the future of
      the field of biochemistry.

PMID- 29048884
TI  - Nanotechnology for Multimodal Synergistic Cancer Therapy.
AB  - The complexity, diversity, and heterogeneity of tumors seriously undermine the
      therapeutic potential of treatment. Therefore, the current trend in clinical
      research has gradually shifted from a focus on monotherapy to combination therapy
      for enhanced treatment efficacy. More importantly, the cooperative enhancement
      interactions between several types of monotherapy contribute to the naissance of
      multimodal synergistic therapy, which results in remarkable superadditive (namely
      "1 + 1 > 2") effects, stronger than any single therapy or their theoretical
      combination. In this review, state-of-the-art studies concerning recent advances
      in nanotechnology-mediated multimodal synergistic therapy will be systematically
      discussed, with an emphasis on the construction of multifunctional nanomaterials
      for realizing bimodal and trimodal synergistic therapy as well as the intensive
      exploration of the underlying synergistic mechanisms for explaining the
      significant improvements in synergistic therapeutic outcome. Furthermore, the
      featured applications of multimodal synergistic therapy in overcoming tumor
      multidrug resistance, hypoxia, and metastasis will also be discussed in detail,
      which may provide new ways for the efficient regression and even elimination of
      drug resistant, hypoxic solid, or distant metastatic tumors. Finally, some design
      tips for multifunctional nanomaterials and an outlook on the future development
      of multimodal synergistic therapy will be provided, highlighting key scientific
      issues and technical challenges and requiring remediation to accelerate clinical
      translation.

PMID- 29048885
TI  - Correction to "Identification of the TyrOH?+ Radical Cation in the Flavoenzyme
      TrmFO".

PMID- 29048886
TI  - A Mild Hydroaminoalkylation of Conjugated Dienes Using a Unified Cobalt and
      Photoredox Catalytic System.
AB  - Metallo-photoredox catalysis has redefined the available bond disconnections in
      the synthetic arsenal. By harnessing the one-electron chemistry of photoredox
      catalysis in tandem with low-valent cobalt catalysts, new methods by which
      functionalities may be stitched together become available. Herein we describe the
      coupling of photoredox-generated alpha-amino radical species with conjugated
      dienes using a unified cobalt and iridium catalytic system in order to access a
      variety of useful homoallylic amines from simple commercially available starting
      materials. We present a series of mechanistic experiments that support the
      intervention of Co-hydride intermediates that undergo diene insertion to generate
      Co-pi-allyl species.

PMID- 29048887
TI  - Fluorescent Sensors Based on Aptamer Self-Assembly.

PMID- 29048888
TI  - Catalysis as an Enabling Science for Sustainable Polymers.
AB  - The replacement of current petroleum-based plastics with sustainable alternatives
      is a crucial but formidable challenge for the modern society. Catalysis presents
      an enabling tool to facilitate the development of sustainable polymers. This
      review provides a system-level analysis of sustainable polymers and outlines key
      criteria with respect to the feedstocks the polymers are derived from, the manner
      in which the polymers are generated, and the end-of-use options. Specifically, we
      define sustainable polymers as a class of materials that are derived from
      renewable feedstocks and exhibit closed-loop life cycles. Among potential
      candidates, aliphatic polyesters and polycarbonates are promising materials due
      to their renewable resources and excellent biodegradability. The development of
      renewable monomers, the versatile synthetic routes to convert these monomers to
      polyesters and polycarbonate, and the different end-of-use options for these
      polymers are critically reviewed, with a focus on recent advances in catalytic
      transformations that lower the technological barriers for developing more
      sustainable replacements for petroleum-based plastics.

PMID- 29048889
TI  - Lipoyl-Homotaurine Derivative (ADM_12) Reverts Oxaliplatin-Induced Neuropathy and
      Reduces Cancer Cells Malignancy by Inhibiting Carbonic Anhydrase IX (CAIX).
AB  - Oxaliplatin (OXA) is a valuable and largely used cancer drug which induces a
      serious and intractable neuropathy. The lipoyl-homotaurine derivative (ADM_12)
      reverts in vivo OXA-induced neuropathy, and it is an effective antagonist of the
      nociceptive sensor channel TRPA1. Unprecedentedly, this safe analgesic showed a
      synergy with OXA in vitro and proved to inhibit CA IX, a relevant therapeutic
      target, clearly interfering with pancreatic cancer cells' aggressiveness.

PMID- 29048890
TI  - Effect of the Urban Heat Island on Aerosol pH.
AB  - The urban heat island (UHI) is a widely observed phenomenon whereby urban
      environments have higher temperatures and different relative humidities than
      surrounding suburban and rural areas. Temperature (T) and relative humidity (RH)
      strongly affect the partitioning of semivolatile species found in the atmosphere,
      such as nitric acid, ammonia, and water. These species are inherently tied to
      aerosol pH, which is a key parameter driving some atmospheric chemical processes
      and environmental effects of aerosols. In this study, we characterized the effect
      of the UHI on aerosol pH in Baltimore, MD, and Chicago, IL. The T and RH
      differences that define the UHI lead to substantial differences in aerosol liquid
      water (ALW) content. The ALW differences produce urban aerosol pH that is
      systematically lower (more acidic) than rural aerosol pH for identical
      atmospheric composition. The UHI in Baltimore and Chicago are most intense during
      the summer and at night, with urban-rural aerosol pH differences in excess of 0.8
      and 0.65 pH units, respectively. The UHI has been observed in cities of all
      sizes: the similarity of our results for cities with different climatologies and
      aerosol compositions suggests that these results have broad implications for
      chemistry occurring in and around urban atmospheres globally.

PMID- 29048892
TI  - Antiplasmodial Chromanes and Chromenes from the Monotypic Plant Species
      Koeberlinia spinosa.
AB  - Nine new compounds containing either a chromane or chromene ring moiety were
      isolated from the monotypic plant Koeberlinia spinosa. Compounds 1-4 are
      chromanes with all possible E and Z isomers of the isoprenoid side chain, with
      compound 5 a methylated derivative of 1. Compounds 6 and 7 were assigned as
      diastereomeric cyclized derivatives of 2 and were probably artifacts formed
      during the extraction or the isolation processes. Compounds 8 and 9 were
      characterized as new chromenes. Structure elucidation of 1-9 was conducted via 1D
      and 2D NMR spectroscopic data interpretation, and absolute configurations were
      determined by ECD spectroscopic analysis. Compounds 2, 5, 6, and 7 had weak
      antiplasmodial activity, while none of the compounds exhibited antiproliferative
      activity. The isolation, structure elucidation, and biological evaluation of
      these compounds are presented.

PMID- 29048893
TI  - Diastereoselective Synthesis of Functionalized Diketopiperazines through Post
      transformational Reactions.
AB  - A diversity-oriented access to diastereoselective arylidene 2,5-diketopiperazines
      is elaborated via a sequential Ugi post-transformation involving catalytic
      cyclization and oxidative Heck reaction sequence. This sequence offers an
      interesting multicomponent entry to a library of 2,5-diketopiperazines and
      arylidene 2,5-diketopiperazines under mild reaction conditions in good to
      excellent yields.

PMID- 29048894
TI  - Immunomodulatory Polyketides from a Phoma-like Fungus Isolated from a Soft Coral.
AB  - Fourteen new polyketides with a trans-fused decalin ring system, libertalides A-N
      (3-16), together with two known analogues, aspermytin A and its acetate (1, 2),
      were isolated from the fermentation extract of a coral-derived Libertasomyces sp.
      fungus. Their relative configurations were elucidated on the basis of detailed
      spectroscopic analysis, and the absolute configurations were determined by TDDFT
      ECD and optical rotation (OR) calculations. The OR of 1 and 2 were found to have
      opposite signs in CH3CN and CHCl3, which was in agreement with the OR
      calculations producing alternating signs for the optical rotation depending on
      the applied conditions. Because the signs of the OR for 1 and 2 showed high
      solvent dependence, they may not be used alone to correlate the absolute
      configurations. Compound 16 displayed structural novelty characterized by an
      alpha-enol ether bridge conjugated with an aldehyde group. In in vitro
      immunomodulatory screening, compounds 1, 4, and 10 significantly induced the
      proliferation of CD3+ T cells, while compounds 2, 7, 11, and 14 significantly
      increased the CD4+/CD8+ ratio at 3 MUM. A preliminary structure-activity analysis
      revealed a crucial role of Delta7 and a terminal OH group in the regulation of
      CD3+ T cell proliferation. This is the first report of immunoregulatory activity
      for metabolites of this kind.

PMID- 29048895
TI  - The Origin of the Non-Additivity in Resonance-Assisted Hydrogen Bond Systems.
AB  - The concept of resonance-assisted hydrogen bond (RAHB) has been widely accepted,
      and its impact on structures and energetics can be best studied computationally
      using the block-localized wave function (BLW) method, which is a variant of ab
      initio valence bond (VB) theory and able to derive strictly electron-localized
      structures self-consistently. In this work, we use the BLW method to examine a
      few molecules that result from the merging of two malonaldehyde molecules. As
      each of these molecules contains two hydrogen bonds, these intramolecular
      hydrogen bonds may be cooperative or anticooperative, depended on their relative
      orientations, and compared with the hydrogen bond in malonaldehyde. Apart from
      quantitatively confirming the concept of RAHB, the comparison of the computations
      with and without pi resonance shows that both sigma-framework and pi-resonance
      contribute to the nonadditivity in these RAHB systems with multiple hydrogen
      bonds.

PMID- 29048896
TI  - Infrared Spectra of the 1-Chloromethyl-1-methylallyl and 1-Chloromethyl-2
      methylallyl Radicals Isolated in Solid para-Hydrogen.
AB  - The reaction of chlorine atoms (Cl) with isoprene (2-methyl-1,3-butadiene, C5H8)
      in solid para-hydrogen (p-H2) matrices at 3.2 K was studied using infrared (IR)
      spectroscopy. Mixtures of C5H8 and Cl2 were codeposited in p-H2 at 3.2 K,
      followed by irradiation with ultraviolet light at 365 nm to induce the
      photodissociation of Cl2 and the subsequent reaction of the Cl atoms with C5H8.
      Upon 365 nm photolysis, a multitude of new lines appeared in the IR spectrum,
      and, based on the secondary photolysis behavior, it was determined that the
      majority of the new lines belong to two distinct chemical species, designated as
      set A (intense lines at 1237.9, 807.8, and 605.6/608.2 cm-1, and several other
      weaker lines) and set B (intense lines at 942.4, 1257.7, 796.7/798.5, 667.9, and
      569.7 cm-1, and several other weaker lines). Quantum-chemical calculations were
      performed at the B3PW91/6-311++G(2d,2p) level for .C5H7 and the four possible
      isomers of the .C5H8Cl radicals, produced from the addition of the Cl atom to the
      four distinct sites of carbon atoms in C5H8, to determine the relative energetics
      and predict IR spectra for each radical. The newly observed lines of sets A and B
      are assigned to the 1-chloromethyl-2-methylallyl radical (addition to carbon 4)
      and the 1-chloromethyl-1-methylallyl radical (addition to carbon 1) according to
      comparison with predicted IR spectra of possible products. The 1-chloromethyl-2
      methylallyl radical and 1-chloromethyl-1-methylallyl radicals were predicted to
      be the most stable, with the latter ~8 kJ mol-1 lower in energy than the former.
      The ratio of the 1-chloromethyl-1-methylallyl to the 1-chloromethyl-2-methylallyl
      radicals is estimated to be (1.2 +/- 0.5):1.0, indicating that the two radicals
      are produced in approximately equal amounts. The exclusive production of the
      radicals involving the addition of the Cl atom to the two terminal carbons of
      isoprene is analogous to what was previously observed for the reaction of Cl
      atoms with trans-1,3-butadiene in solid p-H2.

PMID- 29048897
TI  - Unified Treatment for Plasmon-Exciton Co-driven Reduction and Oxidation
      Reactions.
AB  - Revealing the nature of plasmon-exciton co-driven surface catalytic reactions is
      important and urgent for developing potential applications in energy and
      environmental science. In this work, we propose a mechanism for plasmon-exciton
      co-driven surface catalytic reactions based on our experimental results. We
      provide a method for a unified treatment for reduction and oxidation reactions,
      which not only strongly supports our proposed mechanism but also promotes a
      deeper understanding of plasmon-exciton co-driven surface catalytic reactions.

PMID- 29048898
TI  - Influences of Structural Properties on Stability of Fullerenols.
AB  - Influences of structural properties on the stability of fullerenols are studied
      using experimental techniques including laser-induced dissociation associated
      with a time-of-flight measurement, synchrotron radiation XPS, and FT-IR
      spectroscopy. Stabilities of a family of fullerenols (C60(OH)42, C60(OH)44,
      C60(OH)30, C60(OH)30, C60(OH)32, and C60(OH)36) as functions of structural
      parameters-the hydroxyl number, intensity of the impure group, and the ratio of
      the carbonyl to hydroxyl groups-are investigated. It is found that the molecular
      stability largely depends on the quantity of impure groups, especially the highly
      oxygenated carbons in fullerenols, but less on the hydroxyl number. This is
      different from the previous consideration that the stability of fullerenols
      largely depends on the hydroxyl number. Previously, to gain the larger solubility
      required by practical applications, it was suggested to increase the number of
      the hydroxyl groups. This idea needs to be restudied, because in highly
      hydroxylated fullerenol molecules, the coinstantaneous formation of a large
      amount of impure groups is observed. The use of C60(OH) n>36 in practical
      applications should proceed with caution, since these could lead to unstable open
      cage structures. The results reveal a way of controlling the formation of impure
      groups to gain fullerenols of high stability.

PMID- 29048899
TI  - Matrix Infrared Spectra of Insertion and Metallacyclopropane Complexes [CH3CH2-MH
      and (CH2)2-MH2] Prepared in Reactions of Laser-Ablated Group 3 Metal Atoms with
      Ethane.
AB  - CH3CH2-MH and (CH2)2-MH2 were identified in the matrix IR spectra from reactions
      of laser-ablated group 3 metal atoms with ethane, and they were characterized via
      theoretical investigations. The observed products are the most stable in the
      proposed reaction path. Because of the small number of valence electrons, the
      group 3 metal high oxidation-state complexes are less stable. The C-C insertion
      product [(CH3)2M], which was predicted to be more stable than the observed ones,
      was not observed probably because of the high energy barrier and a likely slower
      rate for insertion into one C-C bond than one of six C-H bonds. The C-C bond of
      the metallacyclopropanes is the shortest among the early transition-metal
      analogues, and its stretching frequencies are the highest, revealing the weakest
      interaction between the metal dihydride and ethylidene groups. The undetected
      ethylidene is not agostic, parallel to the previously examined methylidene.

PMID- 29048900
TI  - Nonstabilized Azomethine Ylides in the Mannich Reaction: Synthesis of 3,3
      Disubstituted Pyrrolidines, Including Oxindole Alkaloids.
AB  - Active methylene compounds react with in situ generated nonstabilized azomethine
      ylides via the domino Mannich reaction-dipolar cycloaddition to form 3,3
      disubstituted pyrrolidines, including oxindole alkaloids. When the starting
      material possesses a single activated hydrogen, the reaction terminates at the
      Mannich base stage. The developed methodology was applied to a short and
      efficient synthesis of (+/-)-horsfiline and N-protected (+/-)-coerulescine.

PMID- 29048901
TI  - Acid Promoted Direct Cross-Coupling of Methyl Ketones with Dimethyl Sulfoxide:
      Access to Ketoallyl Methylsulfides and -sulfones.
AB  - A new strategy to prepare beta-acyl allylic methylsulfides and -sulfones through
      acid promoted direct cross-coupling of methyl ketones with dimethyl sulfoxide
      (DMSO) is reported. The reaction proceeded through the nucleophilic attack of
      enamine intermidiates derived from ketones to in situ generated thionium ion
      species, followed by elimination of methanthiol to give ketoallylic
      methylsulfides. With the prolonged reaction time, such products could be further
      reacted with a methyl sulfonyl radical, which might be generated from a
      methylthiosulfonate species, to afford ketoallylic methylsulfones in high yields.
      Molecular transformations of the allylic methylsulfides were also demonstrated.

PMID- 29048902
TI  - Self-Assembly of Patchy Particles.
AB  - Molecular simulations are performed to study the self-assembly of particles with
      discrete, attractive interaction sites - "patches" - at prescribed locations on
      the particle surface. Chains, sheets, rings, icosahedra, square pyramids,
      tetrahedra, and twisted and staircase structures are obtained through suitable
      design of the surface pattern of patches. Our simulations predict that the
      spontaneous formation of two-dimensional sheets and icosahedra occurs via a first
      order transition while the formation of chains occurs via a continuous disorder
      to-order transition as in equilibrium polymerization. Our results show how
      precise arrangements of patches combined with patch "recognition" or selectivity
      may be used to control the relative position of particles and the overall
      structure of particle assemblies. In this context, patchy particles represent a
      new class of building block for the fabrication of precise structures.

PMID- 29048903
TI  - Functionalized Self-Assembled Monolayers Bearing Diiminate Complexes Immobilized
      through Covalently Anchored Ligands.
AB  - The application of synthetic organic chemistry to the surface chemistry of
      monolayer arrays adds a novel dimension to the power of these systems for surface
      modification. This paper describes the elaboration of simple functionalized
      monolayers into dialdimine and dialdiminate ligands tethered to the monolayer
      surface. These ligands are then used to coordinate metal ions in an effort to
      form diiminate complexes with control over their environment and orientation.
      Ligand anchoring is best achieved through either thiol-ene photochemistry or
      azide-acetylene "click" chemistry. There is an influence of ligand bulk on some
      surface transformations, and in some cases reactions that have been reported to
      be effective on simple, homogeneous monolayer surfaces are not applicable to a
      more complex monolayer environment. The large excess of solution reagents
      relative to monolayer surface functionality adds another measure of difficulty to
      the control of interfacial reactions. In instances where the anchoring chain
      includes functional groups that can directly interact with metal ions, the
      metalation of ligand-bearing surfaces resulted in a higher metal ion content than
      would have been expected from binding only to the diimine ligands.

PMID- 29048904
TI  - Ultrahigh Elastic Strain Energy Storage in Metal-Oxide-Infiltrated Patterned
      Hybrid Polymer Nanocomposites.
AB  - Modulus of resilience, the measure of a material's ability to store and release
      elastic strain energy, is critical for realizing advanced mechanical actuation
      technologies in micro/nanoelectromechanical systems. In general, engineering the
      modulus of resilience is difficult because it requires asymmetrically increasing
      yield strength and Young's modulus against their mutual scaling behavior. This
      task becomes further challenging if it needs to be carried out at the nanometer
      scale. Here, we demonstrate organic-inorganic hybrid composite nanopillars with
      one of the highest modulus of resilience per density by utilizing vapor-phase
      aluminum oxide infiltration in lithographically patterned negative photoresist SU
      8. In situ nanomechanical measurements reveal a metal-like high yield strength
      (~500 MPa) with an unusually low, foam-like Young's modulus (~7 GPa), a unique
      pairing that yields ultrahigh modulus of resilience, reaching up to ~24 MJ/m3 as
      well as exceptional modulus of resilience per density of ~13.4 kJ/kg, surpassing
      those of most engineering materials. The hybrid polymer nanocomposite features
      lightweight, ultrahigh tunable modulus of resilience and versatile nanoscale
      lithographic patternability with potential for application as nanomechanical
      components which require ultrahigh mechanical resilience and strength.

PMID- 29048905
TI  - Disentangling "Bright" and "Dark" Interactions in Ordered Assemblies of Organic
      Semiconductors.
AB  - We report on spatially correlated wavelength-resolved photoluminescence and
      Kelvin probe force microscopy to probe ground state charge-transfer coupling and
      its correlation with pi-stacking order in nanoscale assemblies of a small
      molecule n-type organic semiconductor, tetraazaterrylene (TAT). We find a
      distinct upshift in surface potential contrast (SPC) corresponding to a decrease
      in work function in TAT in the transition from disordered spun-cast films to
      ordered crystalline nanowire assemblies, accompanied by a nanowire size
      dependence in the SPC shift suggesting that the shift depends on both ground
      state charge transfer interaction and a size (volume)-dependent intrinsic doping
      associated with the nitrogen substitutions. For the smallest nanowires studied
      (surface height ~ 10-15 nm), the SPC shift with respect to disordered films is
      +110 meV, in close agreement with recent theoretical calculations. These results
      illustrate how "dark" (ground-state) interactions in organic semiconductors can
      be distinguished from "bright" (excited-state) exciton coupling typically
      assessed by spectral measurements alone.

PMID- 29048906
TI  - Gold-Catalyzed Ring Expansion of Enyne-Lactone: Generation and Transformation of
      2-Oxoninonium.
AB  - An efficient gold-catalyzed ring-expansion reaction of enyne-lactones to form 2
      oxoninonium intermediates is reported. The 2-oxoninonium generated in this work
      could undergo further 6pi electrocyclization and aromatization reaction to
      produce different aromatic compounds.

PMID- 29048907
TI  - Open Cell Aerogel Foams via Emulsion Templating.
AB  - The water-in-oil emulsion-templating method is used in this work for fabrication
      of open cell aerogel foams from syndiotactic polystyrene (sPS). A surfactant
      stabilized emulsion is prepared at 60-100  degrees C by dispersing water in a
      solution of sPS in toluene. sPS gel, formed upon cooling of the emulsion to room
      temperature, locks the water droplets inside the gel. The gel is solvent
      exchanged in ethanol and then dried under supercritical condition of carbon
      dioxide to yield the aerogel foams. The aerogel foams show a significant fraction
      of macropores with a diameter of a few tens of micrometers, defined as macrovoids
      that originated from the emulsified water droplets. In conjunction, customary
      macropores of diameter 50-200 nm are derived from sPS gels. The macrovoids add
      additional openness to the aerogel structures. This paper evaluates the
      structural characteristics of the macrovoids, such as diameter distribution,
      macrovoid interconnect density, and skin layer density, in conjunction with the
      final aerogel foam properties.

PMID- 29048908
TI  - Co-Catalyzed Direct Addition of Allylic C(sp3)-H Bonds to Ketones.
AB  - By using Co(acac)2/Xantphos with AlMe3, the C(sp3)-H bonds of allylarene
      derivatives were cleaved for reaction with various ketones, affording the
      homoallylic alcohols in moderate to good yields. The branch/linear selectivity
      depended on the steric and electronic factors of the ketone electrophiles. The
      intermediate in this reaction is thought to be a low-valent allylcobalt(I)
      species, which exhibits high nucleophilicity toward ketones.

PMID- 29048909
TI  - Rhodium-Catalyzed Direct Ortho C-H Arylation Using Ketone as Directing Group with
      Boron Reagent.
AB  - A general method for selective ortho C-H arylation of ketone, with boron reagent
      enabled by rhodium complexes with excellent yields, is developed. The
      transformation is characterized by the use of air-stable Rh catalyst, high
      monoarylation selectivity, and excellent yields of most of the substrates.

PMID- 29048910
TI  - Solvent Dielectricity-Modulated Helical Assembly and Morphologic Transformation
      of Achiral Surfactant-Inorganic Cluster Ionic Complexes.
AB  - Ionic complexes comprising single/double chain cationic surfactant and Lindqvist
      type polyoxomolybdate anionic cluster were used for controlled self-assembly in
      organic solutions. In the solvent with low dielectric constant the complexes self
      assembled into flat ribbon like lamellar aggregations with an inverse bilayer
      substructure where the cluster located at the middle. Under the condition of
      increased dielectric constant, the solvent triggered the formation of helical
      self-assemblies, which finally transformed from helical ribbons to the flower
      like assemblies due to the bilayer becoming excessively twisted. The self
      assembled morphology and the substructure were characterized by SEM, TEM, and
      XRD. The solvent dielectricity-controlled morphologic transformations modulated
      by the variation of electrostatic interactions between organic cations and
      inorganic polyanions were demonstrated by 1H NMR and IR spectra. The strategy in
      this work represents an effective route in targeting the chirality-directed
      functionalization of inorganic clusters by combining controllable and helical
      assemblies of achiral polyoxometalate complexes in one system.

PMID- 29048911
TI  - Hydroxoiridium-Catalyzed Hydroarylation of Alkynes and Bicycloalkenes with N
      Sulfonylbenzamides.
AB  - Hydroxoiridium complexes efficiently catalyzed the hydroarylation of alkynes and
      bicycloalkenes with N-sulfonylbenzamides via C-H activation to give the
      corresponding ortho-alkenylation and alkylation products in high yields.

PMID- 29048912
TI  - Intermolecular [2 + 2] Cycloaddition of 1,4-Dihydropyridines with Olefins via
      Energy Transfer.
AB  - A highly regio- and diastereoselective visible-light-promoted [2 + 2]
      cycloaddition between readily available 1,4-dihydropyridines and olefins has been
      developed. This strategy is operationally simple and atom-economical and enables
      the construction of strained polysubstituted 2-azabicyclo[4.2.0]octanes with
      three all-carbon quaternary centers with good functional group tolerance. These
      products can be easily converted to various structurally unique derivatives. The
      primary mechanistic studies demonstrated that the reaction proceeds through an
      energy transfer pathway.

PMID- 29048913
TI  - Synthesis of N-Substituted Sulfamate Esters from Sulfamic Acid Salts by
      Activation with Triphenylphosphine Ditriflate.
AB  - A general approach to access sulfamate esters through preparation of sulfamic
      acid salts, subsequent activation with triphenylphosphine ditriflate, and
      nucleophilic trapping is disclosed. The method proceeds in modest to excellent
      yields to incorporate nucleophiles derived from aliphatic alcohols and phenols.
      This approach can be employed to furnish differentially substituted sulfamides.

PMID- 29048914
TI  - Transition in Dynamics as Nanoparticles Jam at the Liquid/Liquid Interface.
AB  - Nanoparticles (NPs) segregated to the liquid/liquid interface form disordered or
      liquid-like assemblies that show diffusive motions in the plane of the interface.
      As the areal density of NPs at the interface increases, the available interfacial
      area decreases, and the interfacial dynamics of the NP assemblies change when the
      NPs jam. Dynamics associated with jamming was investigated by X-ray photon
      correlation spectroscopy. Water-in-toluene emulsions, formed by a self
      emulsification at the liquid/liquid interface and stabilized by ligand-capped
      CdSe-ZnS NPs, provided a simple, yet powerful platform, to investigate NP
      dynamics. In contrast to a single planar interface, these emulsions increased the
      number of NPs in the incident beam and decreased the absorption of X-rays in
      comparison to the same path length in pure water. A transition from diffusive to
      confined dynamics was manifested by intermittent dynamics, indicating a
      transition from a liquid-like to a jammed state.

PMID- 29048915
TI  - Chiral and Racemic Spin Crossover Polymorphs in a Family of Mononuclear Iron(II)
      Compounds.
AB  - Understanding the origin of cooperativity and the equilibrium temperature of
      transition (T1/2) displayed by the spin-crossover (SCO) compounds as well as
      controlling these parameters are of paramount importance for future applications.
      For this task, the occurrence of polymorphism, presented by a number of SCO
      complexes, may provide deep insight into the influence of the supramolecular
      organization on the SCO behavior. In this context, herein we present a novel
      family of mononuclear octahedral FeII complexes with formula cis
      [Fe(bqen)(NCX)2], where bqen is the chelating tetradentate ligand N,N'-bis(8
      quinolyl)ethane-1,2-diamine and X = S, Se. Depending on the preparation method,
      these compounds crystallize in either the orthorhombic or the trigonal symmetry
      systems. While the orthorhombic phase is composed of a racemic mixture of
      mononuclear complexes (polymorph I), the trigonal phase contains only one of the
      two possible enantiomers (Lambda or Delta), thereby generating a chiral crystal
      (polymorph II). The four derivatives undergo SCO behavior with well
      differentiated T1/2 values occurring in the interval 90-233 K. On one hand, T1/2
      is about 110 K (polymorph I) and 87 K (polymorph II) higher for the selenocyanate
      derivatives in comparison to those for their thiocyanate counterparts. These
      differences in T1/2 are ascribed not only to the higher ligand field induced by
      the selenocyanate anion but also to a remarkable difference in the structural
      reorganization of the [FeN6] coordination core upon SCO. Likewise, the higher
      cooperativity observed for the thiocyanate derivatives seems to be related to
      their stronger intermolecular interactions within the crystal. On the other hand,
      T1/2 is about 53 K (thiocyanate) and 29 K (selenocyanate) higher for the trigonal
      polymorph II in comparison to those for the orthorhombic polymorph I. These
      differences, and the small changes observed in cooperativity, stem from the
      slightly different hetero- and homochiral crystal packing generated by the cis
      [Fe(bqen)(NCX)2] molecules, which determines subtle adaptations in the
      intermolecular contacts and the FeII coordination core.

PMID- 29048916
TI  - Reduced Magnetism in Core-Shell Magnetite@MOF Composites.
AB  - The magnetic susceptibility of synthesized magnetite (Fe3O4) microspheres was
      found to decline after the growth of a metal-organic framework (MOF) shell on the
      magnetite core. Detailed structural analysis of the core-shell particles using
      scanning electron microscopy, transmission electron microscopy, atom probe
      tomography, and57Fe-Mossbauer spectroscopy suggests that the distribution of MOF
      precursors inside the magnetic core resulted in the oxidation of the iron oxide
      core.

PMID- 29048917
TI  - A Population-Based Study of the Prevalence of Abnormal Uterine Bleeding and its
      Related Factors among Iranian Reproductive-Age Women: An Updated Data.
AB  - BACKGROUND: Abnormal uterine bleeding (AUB) is one of the most common gynecologic
      complaints among reproductive-age women. The purpose of this study was to
      investigate the prevalence of AUB and its related factors among reproductive age
      Iranian women. METHODS: A population-based cross-sectional study was conducted on
      1393 women aged 15 - 45 years who participated in the Tehran Lipid and Glucose
      Study in 2009 - 2012. FIGO terminology and previous definitions were used for
      classification of AUB. Logistic regression was used to estimate adjusted odds
      ratios (OR) and 95% confidence intervals to check the association between AUB and
      the women's demographic characteristics. P < 0.05 was considered statistically
      significant. RESULTS: A total of 35.8% (95% CI: 31.5% - 40.2%) of the
      participants suffered from one or more types of AUB. About 10.6% (95% CI: 6.3% -
      12.5%) of them had disturbances of regularity and 23.8% (95% CI: 18.4% - 26.1%)
      reported experiencing disturbances of frequency. Also, disturbances of heaviness
      of flow and duration of flow were reported in 16% (95% CI: 12.7% - 19.2%) and
      11.5% (95% CI: 8% - 15.4%), respectively. About 4.3% of the women (95% CI: 2.1% -
      10.5%) reported irregular non-menstrual bleeding. According to previous
      definitions, the prevalence of heavy periods, metrorrhagia, polymenorrhea,
      oligomenorrhea, amenorrhea and inter-menstrual bleeding in reproductive aged
      women was 15.2%, 18.9%, 10.6%, 15.2%, 2.2%, and 4.3%, respectively. In addition,
      the proportions of women with AUB rose in the early and late reproductive years.
      After adjustment of confounders, logistic regression analysis showed that age
      (adjusted OR = 1.08, 95% CI: 1.07 - 3.97, P = 0.03) and BMI (adjusted OR = 1.05,
      95% CI: 1.02 - 3.04, P = 0.04) had statistically significant associations with
      AUB. CONCLUSION: The prevalence of AUB as a possible clinical indicator of
      underlying disorders was high among Iranian reproductive age women. Healthcare
      providers and policy makers are required to acknowledge these disorders and
      provide education and counseling opportunities for the public to inform them when
      and how to seek medical advice.

PMID- 29048918
TI  - Cost-effectiveness of Screening Colonoscopy in Iranian High Risk Population.
AB  - BACKGROUND: Colorectal cancer (CRC) is the fourth most common cancer among men
      and the second among women in Iran. First-Degree Relatives (FDRs) of patients
      with CRC are known to be at higher risk of CRC. The aim of this study was to
      identify the most cost-effective strategy for CRC screening in Iranian high risk
      individuals. METHODS: A Markov model was developed to assess the cost
      effectiveness of six colonoscopy screening strategies for individuals at
      increased risk of CRC because of positive history of the disease in at least one
      first-degree relative in their family. Our strategies included five-yearly or ten
      yearly colonoscopy starting from the age of 40 or 50 and colonoscopy once at 50
      or 55 years. Data were extracted from the published literature, Globocan 2012
      database, and national cancer registry reports. The Markov model contained 11
      mutually exclusive health states. Time horizon of model was life time and cycle
      duration was 1 year. Outcomes included life year gains, Quality Adjusted Life
      Years (QALYs) and costs. The TreeAge Pro software was used for data modeling.
      RESULTS: All six screening strategies increased the life expectancy and QALY and
      were costlier than no screening. The incremental cost per QALY gained for CRC
      screening varied from $489 for one colonoscopy screening per lifetime at 55 years
      to $3,135 for colonoscopy screening every five years starting at the age of 40,
      compared with no screening. When strategies were compared with the next best
      strategy, dominated strategies were removed from analysis, one colonoscopy
      screening per lifetime at 55 years old; or every ten years starting at the age
      40; or every five years starting at age 40 remained with incremental cost
      effective ratios of $489, $2,505, and $26,080 per QALY gained, respectively.
      CONCLUSIONS: CRC colonoscopy screening in high-risk individuals is cost-effective
      in Iran. Colonoscopy screening every 10 years starting at the age of 40 was the
      most cost-effective strategy.

PMID- 29048919
TI  - Does Treatment of Either Hypothyroidy or Hyperthyroidy Affect Diurnal Blood
      Pressure.
AB  - OBJECTIVE: Thyroid hormone has well recognized effects on the cardiovascular
      system. The purpose of this study was to define the influence of treatment of
      either hypothyroidism and hyperthyroidism on the values and circadial variations
      of arterial blood pressure measured by ambulatory blood pressure monitoring.
      MATERIAL AND METHODS: The study was carried out on 30 hypothyroidic and 30
      hyperthyroidic patients without hypertension and 46 healthy participants. First,
      all the parameters of the groups, then blood pressure values obtained by
      ambulatory blood pressure monitoring before and after treatment (thyroid hormone
      replacement with levothyroxine and antithyroid treatment either with
      propylthyrouracil or metimazole) were compared. For statistical examinations,
      Shapiro-Wilk, one-way analysis of variance, Kruskal Wallis, post-hoc Tukey, and
      Wilcoxon Sign tests were used. RESULTS: In the hypothyroid group, 24-hour mean
      and diastolic blood pressure, daytime diastolic blood pressure, nighttime mean,
      systolic and diastolic blood pressures were higher than the control group (P <
      0.05). After treatment, 24-hour, daytime and nighttime systolic and diastolic
      blood pressures diminished. Mean blood pressures diminished only in daytime and
      nighttime. In the hyperthyroid group, 24-hour average and daytime systolic, mean
      blood pressures, and all nighttime blood pressure values were higher than the
      control group (P < 0.05). After treatment, 24-hour and daytime systolic, mean
      blood pressures, all nighttime pressures diminished (P < 0.05). CONCLUSION:
      Throughout 24 hours, in hypothyroidic patients especially higher diastolic and in
      hyperthyroidics especially higher systolic blood pressures were exhibited than
      euthyroid subjects. After treatment of these diseases, ambulatory blood pressure
      values decreased. Early control of thyroid dysfunctions may help to protect
      cardiovascular system from hazardous effects of thyroid dysfunctions and lower
      mortality and morbidity in these patients.

PMID- 29048920
TI  - Different Role of CA1 5HT3 Serotonin Receptors on Memory Acquisition Deficit
      Induced by Total (TSD) and REM Sleep Deprivation (RSD).
AB  - BACKGROUND: Serotonin receptors such as 5-HT3 plays critical role in regulation
      of sleep, wake cycle and cognitive process. Thus, we investigated the role of CA1
      5HT3 serotonin receptors in memory acquisition deficit induced by total sleep
      deprivation (TSD; for 24 hour) and REM sleep deprivation (RSD; for 24 hour). Pain
      perception and locomotor activity were also assessed as factors that may affect
      the memory process. METHODS: Modified water box and multi-platform apparatus were
      used to induce TSD or RSD, respectively. Passive avoidance, hot plate and open
      field devices were used for assessment of memory acquisition, pain and locomotor
      activity, respectively. RESULTS: Totally, 152 male Wistar rats were used in the
      study. Pre-training, intra-CA1 injection of 5-HT3 receptor agonist
      Chlorophenylbiguanide (Mchl; 0.01 and 0.001 ug/rat; P < 0.001) and antagonist Y
      25130 (0.1 ug/rat; P < 0.001) reduced memory acquisition and did not alter pain
      response, while higher dose of both drugs increased locomotor activity in normal
      rats. Both TSD and RSD reduced memory acquisition (P < 0.001) and did not alter
      locomotor activity, while TSD (P < 0.001) but not RSD induced analgesia effect.
      The amnesia induced by TSD was restored by subthreshold dose of Y25130 (0.001
      ug/rat; P < 0.001) but not Mchl (0.0001 ug/rat), while both drugs reversed TSD
      induced analgesia effect (P < 0.01 for Mchl and P < 0.05 for Y25130), and Y25130
      increased locomotor activity in TSD rats (P < 0.05). In RSD rats, subthreshold
      dose of both drugs did not alter memory acquisition deficit and increased
      locomotor activity (P < 0.001 for Mchl and P < 0.01 for Y25130), while the Y25130
      (P < 0.001), but not Mchl induced analgesia in the RSD rats. CONCLUSION: Based on
      the above data, CA1 5HT3 receptors seem to play a critical role in cognitive and
      non-cognitive behaviors induced by TSD and RSD.

PMID- 29048921
TI  - Infrastructures Required for the Expansion of Family Physician Program to Urban
      Settings in Iran.
AB  - INTRODUCTION: Following the implementation of Family Physician (FP) Program in
      rural areas and cities with populations under 20000 in 2005, the Iranian Ministry
      of Health and Medical Education in 2012 decided to implement urban FP in large
      cities with populations more than 20000. Along with the development and
      implementation of urban FP in Iran, local websites and newspapers reflected the
      viewpoints of experts in various levels of health system regarding the various
      stages of Family Medicine (FM) development (from agenda setting to initial stages
      of implementation). This study aimed to explore the major infrastructures
      perceived to be required to achieve desirable implementation of urban FP through
      analyzing experts' viewpoints reflected in the media and interviews. METHODS: In
      a qualitative study, we analyzed the contents of health related national websites
      as well as transcribed interviews with key informants. Documents were collected
      from December 2011 to January 2014 and interviews were conducted from February
      2014 to June 2015. We used mixed thematic approach (inductive and deductive) for
      analysis that was assisted by MAXQDA 12 software. RESULTS: Infrastructures needed
      for the implementation of FP were categorized in five main themes and 23
      subthemes. The themes are: 'Stewardship/governance', 'Actors and stakeholders',
      'structural infrastructure', 'technical infrastructure and needed resources', and
      'information and communication infrastructure'. CONCLUSIONS: Expansion of FP
      program to urban settings needs appropriate attention to the principles of policy
      implementation as well as provision of robust infrastructures. Well-defined
      stewardship, revised approach to financial regulation and payment system,
      stakeholder's commitment to collaboration, policy for conflict resolution, and
      universal insurance coverage are pivotal for the expansion of family physician
      program to the urban settings in Iran.

PMID- 29048922
TI  - An Overview of Tracheal Stenosis Research Trends and Hot Topics.
AB  - BACKGROUND: Tracheal stenosis remains a challenge in the thoracic surgery field.
      Recognizing the hot topics and major concepts in this area would help the health
      policy makers to determine their own priorities and design the effective research
      plans. The present study analyzed and mapped the topics and trends of tracheal
      stenosis studies over time as well as authors' and countries' contributions.
      MATERIALS AND METHODS: Search results were obtained employing Bibexcel. To
      determine cold and hot topics, co-occurrence analysis was applied using three
      international databases 'Web of Science', 'PubMed' and 'Scopus'. Appropriately,
      different categories in the articles such as keywords, authors, and countries
      were explored via VOSviewer and NetDraw. Afterward, the trends of research topics
      were depicted in four time-intervals from 1945 to 2015 by ten co-occurrence
      terms. RESULTS: The majority of articles were limited to case series and
      retrospective studies. The studies had been conducted less frequently on
      prevention, risk factors and incidence determination but extensively on treatment
      and procedures. Based on the articles indexed in WOS, 45 countries and 8,260
      authors have contributed to scientific progress in this field. The highest degree
      of cooperation occurred between the USA and England with 15 common papers.
      CONCLUSIONS: Most of the published literature in tracheal stenosis research field
      was about surgical and non-surgical treatments. Conducting the screening and
      prevention studies would diminish the burden of this disease on the health system
      as well as the patients and their families' well-being.

PMID- 29048923
TI  - Protocol Design for Large-Scale Cross-Sectional Studies of Surveillance of Risk
      Factors of Non-Communicable Diseases in Iran: STEPs 2016.
AB  - INTRODUCTION: The rise in non-communicable diseases (NCDs) has gained increasing
      attention. There is a great need for reliable data to address such problems.
      Here, we describe the development of a comprehensive set of executive and
      scientific protocols and instructions of STEPs 2016. METHODS/DESIGN: This is a
      large-scale cross-sectional study of Surveillance of Risk Factors of NCDs in
      Iran. Through systematic proportional to size cluster random sampling, 31,050
      participants enrolled in three sequential processes, of completing
      questionnaires; physical measurements, and lab assessment. RESULTS: Out of 429
      districts, samples were taken from urban and rural areas of 389 districts. After
      applying sampling weight to the samples, comparing the distribution of population
      and samples, compared classification was determined in accordance with the age
      and sex groups. Out of 31,050 expected participants, 30,541 participant completed
      questionnaires (52.31% female). For physical measurements and lab assessment, the
      cases included 30,042 (52.38% female) and 19,778 (54.04% female), respectively.
      DISCUSSION: There is an urgent need to focus on reviewing trend analyses of
      NCDs.To the best of our knowledge, the present study is the first comprehensive
      experience on systematic electronic national survey. The results could be also
      used for future complementary studies.

PMID- 29048924
TI  - De novo Mutation in CACNA1S Gene in a 20-Year-Old Man Diagnosed with Metabolic
      Myopathy.
AB  - The calcium channel, voltage-dependent, L-type, alpha 1S subunit (CACNA1S) gene
      encodes a skeletal Ca2+ channel which is involved in calcium-dependent processes
      such as muscle contraction and neurotransmitter release. Mutations in this gene
      have been accompanied by hypo- and normokalemic periodic paralysis, thyrotoxic
      periodic paralysis, and susceptibility to malignant hyperthermia. We report the
      clinical and genetic findings in a patient diagnosed with metabolic myopathy who
      had episodic attacks of muscle pain and weakness but with no family background of
      the disease. Next-generation sequencing (NGS) using a panel targeting metabolic
      myopathy and myotonia genes identified a de novo heterozygous pathogenic variant
      c.3724A>G, p.Arg1242Gly, in exon 30 of CACNA1S. As the second report of this
      variant, this case may broaden the CACNA1S-related disease spectrum to include
      normokalemic periodic paralysis.

PMID- 29048925
TI  - Photoclinic.

PMID- 29048926
TI  - Kheyr-on-Nessa Amoli, An Iranian Lady Physician in the Gurkani Court of India.
AB  - The popularity of the science of medicine in the Gurkani Court of India relied on
      the presence and scientific work of Iranian scholars. Iranian women, like men,
      enjoyed this area of science and were also actively involved in social issues.
      The remarkable participation of Iranian female physicians in some medical fields,
      such as issues and care in pregnancy, child-bearing, and baby care, is among
      their scientific contributions to the changes and growing trends in medicine.
      These affairs were monopolized by women who held this knowledge for centuries.
      One of the women who was considerably successful in this field was Zat-on-Nessa
      Amoli, titled Kheyr-on-Nessa, a seventeenth-century female Iranian physician.
      This research aimed to study the contributions and scientific life of this poet
      and Iranian physician based on historical documents and texts, considering the
      research on the science and knowledge of medicine.

PMID- 29048928
TI  - Epidemiology of Shoulder and Elbow Injuries Among United States High School
      Baseball Players: School Years 2005-2006 Through 2014-2015.
AB  - BACKGROUND: Shoulder and elbow injuries are common in young athletes, especially
      high school baseball players. Understanding the risk factors associated with
      baseball injuries is an essential first step in the development of injury
      prevention strategies. PURPOSE: To provide a comprehensive understanding of the
      epidemiology of shoulder and elbow injuries among high school baseball players in
      the United States. STUDY DESIGN: Descriptive epidemiological study. METHODS:
      Baseball-related injury data were obtained from the National High School Sports
      Related Injury Surveillance Study using High School RIO (Reporting Information
      Online), an Internet-based sports injury surveillance system. Athletic trainers
      from high schools across the country uploaded data regarding athlete-exposures
      (AEs) (defined as practice or game participation) and shoulder and elbow injuries
      from the school years 2005-2006 through 2014-2015. RESULTS: A total of 241
      shoulder injuries and 150 elbow injuries occurred during 1,734,198 AEs during the
      study period, for an overall shoulder injury rate of 1.39 per 10,000 AEs and an
      overall elbow injury rate of 0.86 per 10,000 AEs. The overall rates of injury
      were higher in competitions compared with practices for shoulders (rate ratio,
      1.44; 95% CI, 1.11-1.85) and elbows (rate ratio, 2.15; 95% CI, 1.56-2.96). The
      majority of shoulder (39.6%) and elbow (56.9%) injuries were sustained by
      pitchers, and most injuries were chronic and caused by overuse. Position players
      were more likely to sustain injuries by contact with the playing surface or
      apparatus. For pitchers, muscle strains were the most common shoulder injuries
      (38.7%), while ligament sprains were the most common elbow injuries (42.7%). The
      majority of pitchers with shoulder (70.8%) and elbow (64.6%) injuries returned to
      play within 21 days. Among pitchers, a higher proportion of elbow injuries
      (11.4%) resulted in medical disqualification compared with shoulder injuries
      (5.6%). Among pitchers, the majority of shoulder (89.2%) and elbow (96.4%)
      injuries were managed nonsurgically. CONCLUSION: Shoulder and elbow injury rates
      and patterns in high school baseball players differed between field positions
      (pitchers vs position players) and by type of exposure (practice vs competition).
      This study suggests several areas of emphasis for targeted injury prevention
      interventions, most notably limiting fatigue and preventing overuse injuries.

PMID- 29048929
TI  - The Effect of Hamstring Tendon Autograft Harvest on the Restoration of Knee
      Stability in the Setting of Concurrent Anterior Cruciate Ligament and Medial
      Collateral Ligament Injuries.
AB  - BACKGROUND: A hamstring autograft is commonly used in anterior cruciate ligament
      (ACL) reconstruction (ACLR); however, there is evidence to suggest that the
      tendons harvested may contribute to medial knee instability. HYPOTHESIS: We
      tested the hypothesis that the gracilis (G) and semitendinosus (ST) tendons
      significantly contribute to sagittal, coronal, and/or rotational knee stability
      in the setting of ACLR with a concurrent partial medial collateral ligament (MCL)
      injury. STUDY DESIGN: Controlled laboratory study. METHODS: Twelve human
      cadaveric knees were subject to static forces applied to the tibia including an
      anterior-directed force as well as varus, valgus, and internal and external
      rotation moments to quantify laxity at 0 degrees , 30 degrees , 60 degrees , and
      90 degrees  of flexion. The following ligament conditions were tested on each
      specimen: (1) ACL intact/MCL intact, (2) ACL deficient/MCL intact, (3) ACL
      deficient/partial MCL injury, and (4) ACLR/partial MCL injury. To quantify the
      effect of muscle loads, the quadriceps, semimembranosus, biceps femoris,
      sartorius (SR), ST, and G muscles were subjected to static loads. The loads on
      the G, ST, and SR could be added or removed during various test conditions. For
      each ligament condition, the responses to loading and unloading the G/ST and SR
      were determined. Three-dimensional positional data of the tibia relative to the
      femur were recorded to determine tibiofemoral rotations and translations.
      RESULTS: ACLR restored anterior stability regardless of whether static muscle
      loads were applied. There was no significant increase in valgus motion after ACL
      transection. However, when a partial MCL tear was added to the ACL injury, there
      was a 30% increase in valgus rotation ( P < .05). ACLR restored valgus stability
      toward that of the intact state when the G/ST muscles were loaded. A load on the
      SR muscle without a load on the G/ST muscles restored 19% of valgus rotation;
      however, it was still significantly less stable than the intact state.
      CONCLUSION: After ACLR in knees with a concurrent partial MCL injury, the absence
      of loading on the G/ST did not significantly alter anterior stability. Simulated
      G/ST harvest did lead to increased valgus motion. These results may have
      important clinical implications and warrant further investigation to better
      outline the role of the medial hamstrings, particularly among patients with a
      concomitant ACL and MCL injury. CLINICAL RELEVANCE: A concurrent ACL and MCL
      injury is a commonly encountered clinical problem. Knowledge regarding the
      implications of hamstring autograft harvest techniques on joint kinematics may
      help guide management decisions.

PMID- 29048927
TI  - Early Origins of Asthma. Role of Microbial Dysbiosis and Metabolic Dysfunction.

PMID- 29048930
TI  - How Would You Grade Our Progress in Primary Graft Dysfunction after Lung
      Transplantation?

PMID- 29048931
TI  - Breathing Easier: A Well-tolerated Corrector for F508del.

PMID- 29048932
TI  - Cardio-ankle vascular index value in dyslipidemia patients affected by
      cardiovascular risk factors.
AB  - BACKGROUND: Increased arterial stiffness is an independent cardiovascular risk
      factor in smokers or patients with diabetes mellitus and hypertension. Cardio
      ankle vascular index (CAVI) is an index of arterial stiffness and
      atherosclerosis. One of the most important risk factors of the causes of
      atherosclerosis is dyslipidemia(DLP). However, there was a little research about
      which influence factors such as: hypertension, diabetes mellitus, and smoking
      could contribute to the atherosclerosis in the subjects withDLP. METHODS: A total
      of 649 subjects with DLP (Male328/Female321) from Vascular Medicine of Peking
      University Shougang Hospital were examined, with a median age of 66 and 5-95
      percentile range 47.0-83.5 years. Fasting plasma glucose (FPG), total cholesterol
      (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG) were
      analyzed by colorimetric enzymatic assays with the use of an auto analyzer
      (HITACHI-7170, Hitachi, Tokyo, Japan).CAVI was measured by VS-1000 apparatus.
      RESULTS: CAVI correlated significantly with age (p<0.001), Systolic (p<0.001)
      blood pressure(BP), Total cholesterol (p<0.001), LDL-cholesterol
      (p<0.001),Triglycerides (p<0.001) . There was no significant difference in CAVI
      between smokers and non-smokers (p = 0.08) and between statin-treated subjects
      than in those without statins (p = 0.247). CAVI was significantly higher in
      subjects with hypertension than in the normotensive group (p<0.001) and in
      mellitus subjects than in those without mellitus (p<0.001);however, CAVI values
      adjusted for age was higher only in hypertension than in the normotensive group
      (p<0.001). CONCLUSIONS: Our study demonstrated that CAVI value in DLP patients is
      not significantly affected by diabetes mellitus and smoking, but is increased by
      hypertension.

PMID- 29048933
TI  - The Association Between Video Game Play and Cognitive Function: Does Gaming
      Platform Matter?
AB  - Despite consumer growth, few studies have evaluated the cognitive effects of
      gaming using mobile devices. This study examined the association between video
      game play platform and cognitive performance. Furthermore, the differential
      effect of video game genre (action versus nonaction) was explored. Sixty
      undergraduate students completed a video game experience questionnaire, and we
      divided them into three groups: mobile video game players (MVGPs),
      console/computer video game players (CVGPs), and nonvideo game players (NVGPs).
      Participants completed a cognitive battery to assess executive function, and
      learning and memory. Controlling for sex and ethnicity, analyses showed that
      frequent video game play is associated with enhanced executive function, but not
      learning and memory. MVGPs were significantly more accurate on working memory
      performances than NVGPs. Both MVGPs and CVGPs were similarly associated with
      enhanced cognitive function, suggesting that platform does not significantly
      determine the benefits of frequent video game play. Video game platform was found
      to differentially associate with preference for action video game genre and
      motivation for gaming. Exploratory analyses show that sex significantly effects
      frequent video game play, platform and genre preference, and cognitive function.
      This study represents a novel exploration of the relationship between mobile
      video game play and cognition and adds support to the cognitive benefits of
      frequent video game play.

PMID- 29048934
TI  - Recovery high schools may be a key component of youth recovery support services.

PMID- 29048935
TI  - Chimeric antigen receptor-T cell therapy for solid tumors require new clinical
      regimens.
AB  - INTRODUCTION: Chimeric antigen receptor modified T cell (CAR-T) therapy has
      achieved encouraging breakthroughs in the treatment of hematological
      malignancies. Nevertheless, this success has not yet been extrapolated to solid
      tumors. This review focuses on new clinical regimens that could improve the
      therapeutic efficacy of CAR-T in solid tumors. Areas covered: Herein, the authors
      reviewed recent clinical trials using CAR-T therapies for the treatment of solid
      tumors. Specifically, this review covered the following areas: (1) the current
      status of CAR-T cells in the treatment of solid tumors; (2) the major factors
      constraining the efficacy of CAR-T cells in solid tumors; and (3) opinions
      regarding the future of CAR-T as a treatment for solid tumors. Expert commentary:
      While some recent studies have shown promising results, the ultimate success of
      CAR-T therapies in solid tumor patients will require the following improvements
      to clinical regimens: (1) local delivery of CAR-T cells; (2) combination of CAR-T
      cells with chemotherapeutic drugs to treat metastatic tumors; (3) combination of
      CAR-T with immune checkpoint inhibitors; (4) combination therapy using CAR-T
      cells targeting two different antigens; and (5) the use of CAR-T as a strategy to
      prevent tumor recurrence and metastasis after radical resection.

PMID- 29048936
TI  - Computed tomography in hypersensitivity pneumonitis: main findings, differential
      diagnosis and pitfalls.
AB  - INTRODUCTION: Hypersensitivity pneumonitis (HP) is a disease with variable
      clinical presentation in which inflammation in the lung parenchyma is caused by
      the inhalation of specific organic antigens or low molecular weight substances in
      genetically susceptible individuals. Alterations of the acute, subacute and
      chronic forms may eventually overlap, and the diagnosis based on temporality and
      presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more
      feasible and useful in clinical practice. Differential diagnosis of chronic HP
      with other interstitial fibrotic diseases is challenging due to the overlap of
      the clinical history, and the functional and imaging findings of these
      pathologies in the terminal stages. Areas covered: This article reviews the
      essential features of HP with emphasis on imaging features. Moreover, the main
      methodological limitations of high-resolution computed tomography (HRCT)
      interpretation are discussed, as well as new perspectives with volumetric
      quantitative CT analysis as a useful tool for retrieving detailed and accurate
      information from the lung parenchyma. Expert commentary: Mosaic attenuation is a
      prominent feature of this disease, but air trapping in chronic HP seems
      overestimated. Quantitative analysis has the potential to estimate the
      involvement of the pulmonary parenchyma more accurately and could correlate
      better with pulmonary function results.

PMID- 29048937
TI  - Executive Summary of the NHLBI Workshop Report: Leveraging Current Scientific
      Advancements to Understand Sarcoidosis Variability and Improve Outcomes.
AB  - Sarcoidosis is a systemic granulomatous disease that primarily affects the lung;
      it is associated with significant disparities, more commonly impacting those in
      the prime of their lives (age 20-50 yr, with a second peak after age 60 yr),
      black individuals, and women. However, the burden of disease, the ability to
      diagnose and prognose organ involvement and course, as well as specific treatment
      options, management options, and disease pathogenesis remain poorly understood.
      As a result, the National Heart, Lung, and Blood Institute undertook a
      sarcoidosis workshop, "Leveraging Current Scientific Advancements to Understand
      Sarcoidosis Variability and Improve Outcomes," to help address these issues by
      defining the scientific and clinical priorities to improve sarcoidosis care. The
      overarching recommendations from this workshop are outlined in the following
      summary and detailed in the accompanying articles. The recommendations included
      establishing collaborations and networks to conduct research based on consensus
      definitions of disease phenotypes and standards of care, and to provide clinical
      outreach to areas with a burden of disease to improve care. These collaborative
      networks would also serve as the hub to conduct clinical trials of devastating
      phenotypes (e.g., cardiac, neurologic, and fibrotic disease) not only for
      treatment but to enhance our understanding of the burden of disease. In addition,
      the networks would be used to leverage state-of-the-art "omics" and systems
      biology research, as well as other studies to advance understanding of disease
      pathogenesis, and development of biomarkers and therapeutic targets, with a goal
      to translate this information to improve care of individuals with sarcoidosis.

PMID- 29048938
TI  - Cybercrime Victimization and Subjective Well-Being: An Examination of the
      Buffering Effect Hypothesis Among Adolescents and Young Adults.
AB  - The wealth of beneficial tools for online interaction, consumption, and access to
      others also bring new risks for harmful experiences online. This study examines
      the association between cybercrime victimization and subjective well-being (SWB)
      and, based on the buffering effect hypothesis, tests the assumption of the
      protective function of social belonging in cybercrime victimization. Cross
      national data from the United States, United Kingdom, Germany, and Finland (N =
      3,557; Internet users aged 15-30 years; 49.85 percent female) were analyzed using
      descriptive statistics and main and moderation effect models. Results show that
      cybercrime victimization has a negative association with SWB after adjusting for
      a number of confounding factors. This association concerns both general
      cybercrime victimization and subcategories such as victimization to offensive
      cybercrime and cyberfraud. In line with the buffering effect hypothesis, social
      belonging to offline groups was shown to moderate the negative association
      between SWB and cybercrime victimization. The same effect was not found in the
      social belonging to online groups. Overall, the study indicates that, analogously
      to crime victimization in the offline context, cybercrime is a harmful experience
      whose negative effects mainly concern those users who have weak social ties
      offline to aid in coping with such stressors.

PMID- 29048940
TI  - A CpGCluster-Teaching-Learning-Based Optimization for Prediction of CpG Islands
      in the Human Genome.
AB  - Many CpG island detection methods have been proposed based on sliding window and
      clustering technology, but the accuracy of these methods is proportional to the
      time required. Therefore, an accurate and rapid method for identifying CpG
      islands remains an important challenge in the complete human genome. We propose a
      hybrid method CpGTLBO to detect the CpG islands in the human genome. The method
      uses the clustering approach and the teaching-learning-based optimization (TLBO)
      algorithm. The clustering approach is used to detect CpG island candidates, and
      it can effectively reduce the huge volume of unnecessary DNA fragments. TLBO was
      used to accurately predict CpG islands among promising CpG island candidates. A
      comparison based on six contig data sets and a whole human genome analysis showed
      that the identifying stability of CpGTLBO outperformed eight existing methods in
      terms of sensitivity (SN), specificity (SP), accuracy (ACC), performance
      coefficient (PC), and correlation coefficient (CC) and processing time. Results
      indicated that ClusterTLBO can effectively overcome the drawbacks and maintain
      the advantages in both the CpGcluster and TLBO.

PMID- 29048939
TI  - Supporting Law Enforcement Personnel Working with Distressing Material Online.
AB  - This study aimed to expand on previous research by gathering international data
      on key stressors impacting on computer forensic investigators who are exposed to
      child exploitation material (CEM) as part of their role. Semistructured
      interviews were conducted with five members of law enforcement (LE) working in
      this area, from five independent and internationally separated organizations. The
      results of these interviews were explored using thematic analysis. The three key
      themes identified were "stressors related to work investigating CEM online,"
      "strategies for mediating stress related to investigating CEM online," and
      "training to investigate CEM online." Investigators of CEM online may experience
      stress from several sources, including but not limited to stress from exposure to
      the material. Other factors such as poor management, high workloads, and limited
      resources may also result in stress, and these stressors may be mediated to an
      extent. Recommendations for training, resources, psychological support, and
      management practices emerged from the research. Such strategies may reduce stress
      experienced by investigators in this role. This study furthers understanding by
      conducting an international examination of multiple centers. Identification of
      common themes and stressors identified by LE personnel in multiple countries can
      help in the development of international standards and guidelines in training and
      stress management.

PMID- 29048941
TI  - Patient Perceptions of the Adequacy of Supplemental Oxygen Therapy. Results of
      the American Thoracic Society Nursing Assembly Oxygen Working Group Survey.
AB  - RATIONALE: Pulmonary clinicians and patients anecdotally report barriers to home
      supplemental oxygen services including inadequate supply, unacceptable portable
      options, and equipment malfunction. Limited evidence exists to describe or
      quantify these problems. OBJECTIVES: To describe the frequency and type of
      problems experienced by supplemental oxygen users in the United States. METHODS:
      The Patient Supplemental Oxygen Survey, a self-report questionnaire, was posted
      on the American Thoracic Society Public Advisory Roundtable and patient and
      health care-affiliated websites. Respondents were invited to complete the
      questionnaire, using targeted e-mail notifications. Data were analyzed using
      descriptive statistics, paired t tests, and chi2 analysis. RESULTS: In total,
      1,926 responses were analyzed. Most respondents reported using oxygen 24 h/d, for
      1-5 years, and 31% used high flow with exertion. Oxygen use varied, with only 29%
      adjusting flow rates based on oximeter readings. The majority (65%) reported not
      having their oxygen saturation checked when equipment was delivered. Sources of
      instruction included the delivery person (64%), clinician (8%), and no
      instruction (10%). Approximately one-third reported feeling "very" or "somewhat"
      unprepared to operate their equipment. Fifty-one percent of the patients reported
      oxygen problems, with the most frequent being equipment malfunction, lack of
      physically manageable portable systems, and lack of portable systems with high
      flow rates. Most respondents identified multiple problems (average, 3.6 +/- 2.3;
      range, 1-12) in addition to limitations in activities outside the home because of
      inadequate portable oxygen systems (44%). Patients living in Competitive Bidding
      Program areas reported oxygen problems more often than those who did not (55%
      [389] vs. 45% [318]; P = 0.025). Differences in sample characteristics and oxygen
      problems were noted across diagnostic categories, with younger, dyspneic, high
      flow users, and respondents who did not receive oxygen education, relating more
      oxygen problems. Respondents reporting oxygen problems also experienced increased
      health care resource utilization. CONCLUSIONS: Supplemental oxygen users
      experience frequent and varied problems, particularly a lack of access to
      effective instruction and adequate portable systems. Initiatives by professional
      and patient organizations are needed to improve patient education, and to promote
      access to equipment and services tailored to each patient's needs.

PMID- 29048942
TI  - Comparison of 2 Exercise Rehabilitation Programs for Multidirectional Instability
      of the Glenohumeral Joint: A Randomized Controlled Trial.
AB  - BACKGROUND: The recommended initial treatment for multidirectional instability
      (MDI) of the shoulder is a rehabilitation program, yet there is very low-quality
      evidence to support this approach. Purpose/Hypothesis: The purpose was to compare
      the Watson MDI program and Rockwood Instability program among patients with
      nontraumatic, nonstructural MDI. The hypothesis was that the Watson MDI program
      would produce clinically and statistically superior outcomes over the Rockwood
      Instability program. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 2. METHODS: Forty-one participants with MDI were randomly allocated to
      the Watson MDI or Rockwood Instability program. Participants attended 12 weekly
      physiotherapy sessions for exercise prescription. Outcomes were assessed at
      baseline and 6, 12, and 24 weeks after randomization. Primary outcomes were the
      Melbourne Instability Shoulder Score (MISS) and the Western Ontario Shoulder
      Index (WOSI). Secondary outcomes included the Orebro Musculoskeletal Pain
      Questionnaire, pain, muscle strength, scapular upward rotation, scapular
      coordinates, global rating of change, satisfaction scales, limiting angle in
      abduction range, limiting factor in abduction range, and incidence of
      dislocation. Primary analysis was by intention to treat based on linear mixed
      models. RESULTS: Between-group differences showed significant effects favoring
      the Watson program for the WOSI (effect size [ES], 11.1; 95% CI, 1.9-20.2; P =
      .018) and for the limiting factor in abduction (ES, 0.1; 95% CI, 0.0-1.6; P =
      .023) at 12 weeks, and for the WOSI (ES, 12.6; 95% CI, 3.4-21.9; P =. 008), MISS
      (ES, 15.4; 95% CI, 5.9-24.8; P = .002), and pain (ES, -2.0; CI: -2.3 to -0.7, P =
      .003) at 24 weeks. CONCLUSION: For people with MDI, 12 sessions of the Watson MDI
      program were more effective than the Rockwood program at 12- and 24-week follow
      up. Registration: ACTRN12613001240730 (Australian New Zealand Clinical Trials
      Registry).

PMID- 29048943
TI  - Prognostic value of the combination of serum levels of vascular endothelial
      growth factor, C-reactive protein and contrast-enhanced ultrasound in patients
      with primary liver cancer who underwent transcatheter arterial chemoembolization.
AB  - BACKGROUND: This study aimed to evaluate the prognostic value of the combination
      of serum levels of vascular endothelial growth factor (VEGF), C-reactive protein
      (CRP), and contrast-enhanced ultrasound (CEUS) in patients with primary liver
      cancer (PLC) after transcatheter arterial chemoembolization (TACE). METHODS:
      Overall, 287 PLC patients who had undergone TACE were allocated into recurrence
      and non-recurrence groups. One day before and seven days after TACE, CEUS was
      performed, and serum VEGF and CRP levels were determined. All patients were
      assigned into either a short time-to-radiologic progression (TTRP) group (TTRP <=
      12 months) or a long TTRP group (TTRP > 12 months). RESULTS: Serum VEGF and CRP
      levels were higher in the recurrence group than the non-recurrence group after
      TACE. The sensitivity and specificity of CEUS parameters, serum VEGF and CRP
      levels, and the three combined, were utilized for the purposes of predicting the
      postoperative recurrences of PLC, which were 80.9% and 87.8%, 81.7% and 71.5%,
      67.0% and 69.8%, and 87.8% and 90.1%, respectively. CONCLUSION: This study
      demonstrated that high serum levels of both VEGF and CRP in addition to a low
      time-to-peak (TTP) value in CEUS were indicators for poor prognosis in PLC
      patients.

PMID- 29048944
TI  - Risk Factors for Social Networking Site Scam Victimization Among Malaysian
      Students.
AB  - Social networking sites (SNSs) can provide cybercriminals with various
      opportunities, including gathering of user data and login credentials to enable
      fraud, and directing of users toward online locations that may install malware
      onto their devices. The techniques employed by such cybercriminals can include
      clickbait (text or video), advertisement of nonexistent but potentially desirable
      products, and hoax competitions/giveaways. This study aimed to identify risk
      factors associated with falling victim to these malicious techniques. An online
      survey was completed by 295 Malaysian undergraduate students, finding that more
      than one-third had fallen victim to SNS scams. Logistic regression analysis
      identified several victimization risk factors including having higher scores in
      impulsivity (specifically cognitive complexity), using fewer devices for SNSs,
      and having been on an SNS for a longer duration. No reliable model was found for
      vulnerability to hoax valuable gift giveaways and "friend view application"
      advertising specifically, but vulnerability to video clickbait was predicted by
      lower extraversion scores, higher levels of openness to experience, using fewer
      devices, and being on an SNS for a longer duration. Other personality traits were
      not associated with either overall victimization susceptibility or increased risk
      of falling victim to the specific techniques. However, age approached
      significance within both the video clickbait and overall victimization models.
      These findings suggest that routine activity theory may be particularly
      beneficial in understanding and preventing SNSs scam victimization.

PMID- 29048945
TI  - Cell Density Affects the Detection of Chk1 Target Engagement by the Selective
      Inhibitor V158411.
AB  - Understanding drug target engagement and the relationship to downstream
      pharmacology is critical for drug discovery. Here we have evaluated target
      engagement of Chk1 by the small-molecule inhibitor V158411 using two different
      target engagement methods (autophosphorylation and cellular thermal shift assay
      [CETSA]). Target engagement measured by these methods was subsequently related to
      Chk1 inhibitor-dependent pharmacology. Inhibition of autophosphorylation was a
      robust method for measuring V158411 Chk1 target engagement. In comparison, while
      target engagement determined using CETSA appeared robust, the V158411 CETSA
      target engagement EC50 values were 43- and 19-fold greater than the
      autophosphorylation IC50 values. This difference was attributed to the higher
      cell density in the CETSA assay configuration. pChk1 (S296) IC50 values
      determined using the CETSA assay conditions were 54- and 33-fold greater than
      those determined under standard conditions and were equivalent to the CETSA EC50
      values. Cellular conditions, especially cell density, influenced the target
      engagement of V158411 for Chk1. The effects of high cell density on apparent
      compound target engagement potency should be evaluated when using target
      engagement assays that necessitate high cell densities (such as the CETSA
      conditions used in this study). In such cases, the subsequent relation of these
      data to downstream pharmacological changes should therefore be interpreted with
      care.

PMID- 29048946
TI  - How Is Frustration Related to Online Gamer Loyalty? A Synthesis of Multiple
      Theories.
AB  - Online games can frustrate their gamers, but little was known about how such
      frustration impacts gamer loyalty. Because novice and experienced gamers may
      respond differently to frustration, this study investigates how gamers'
      frustration influences their loyalty and how this influence may differ between
      novice and experienced gamers. Because of the complexity of this issue, multiple
      theories were synthesized to develop the theoretical model. This study collected
      responses from 558 online gamers. Findings indicate that frustration is
      positively related to novice gamers' participation in task teams, and
      subsequently their loyalty. However, frustration is negatively related to the
      self-efficacy of experienced gamers and to their loyalty.

PMID- 29048947
TI  - Emergence of mcr-1 Producing Salmonella enterica serovar Typhimurium from Retail
      Meat: First Detection in Brazil.

PMID- 29048948
TI  - The spectrum of sickle hemoglobin-related nephropathy: from sickle cell disease
      to sickle trait.
AB  - INTRODUCTION: Renal dysfunction is among the most common complication of sickle
      cell disease (SCD), from hyposthenuria in children to progression to overt
      chronic kidney disease (CKD) in young adults. Emerging evidence now suggests that
      sickle hemoglobin-related nephropathy extends to individuals with sickle cell
      trait (SCT). Areas covered: This review will highlight the pathophysiology,
      epidemiology, and management recommendations for sickle hemoglobin-related
      nephropathy in both SCD and SCT. In addition, it will focus on the major
      demographic and genetic modifiers of renal disease in sickling
      hemoglobinopathies. Expert commentary: Studies have elucidated the course of
      renal disease in SCD; however, the scope and age of onset of renal dysfunction in
      SCT has yet to be determined. In SCD, several modifiers of renal disease - such
      as alpha-thalassemia, hemoglobin F, APOL1 and HMOX1 - have been described and
      provide an opportunity for a precision medicine approach to risk stratify
      patients who may benefit from early intervention. Extrapolating from this
      literature may also provide insight into the modifiers of renal disease in SCT.
      Further studies are needed to determine the optimal treatment for sickle
      hemoglobin-related nephropathy.

PMID- 29048949
TI  - Discovering Pediatric Asthma Phenotypes on the Basis of Response to Controller
      Medication Using Machine Learning.
AB  - RATIONALE: Pediatric asthma has variable underlying inflammation and symptom
      control. Approaches to addressing this heterogeneity, such as clustering methods
      to find phenotypes and predict outcomes, have been investigated. However,
      clustering based on the relationship between treatment and clinical outcome has
      not been performed, and machine learning approaches for long-term outcome
      prediction in pediatric asthma have not been studied in depth. OBJECTIVES: Our
      objectives were to use our novel machine learning algorithm, predictor pursuit
      (PP), to discover pediatric asthma phenotypes on the basis of asthma control in
      response to controller medications, to predict longitudinal asthma control among
      children with asthma, and to identify features associated with asthma control
      within each discovered pediatric phenotype. METHODS: We applied PP to the
      Childhood Asthma Management Program study data (n = 1,019) to discover phenotypes
      on the basis of asthma control between assigned controller therapy groups
      (budesonide vs. nedocromil). We confirmed PP's ability to discover phenotypes
      using the Asthma Clinical Research Network/Childhood Asthma Research and
      Education network data. We next predicted children's asthma control over time and
      compared PP's performance with that of traditional prediction methods. Last, we
      identified clinical features most correlated with asthma control in the
      discovered phenotypes. RESULTS: Four phenotypes were discovered in both datasets:
      allergic not obese (A+/O-), obese not allergic (A-/O+), allergic and obese
      (A+/O+), and not allergic not obese (A-/O-). Of the children with well-controlled
      asthma in the Childhood Asthma Management Program dataset, we found more nonobese
      children treated with budesonide than with nedocromil (P = 0.015) and more obese
      children treated with nedocromil than with budesonide (P = 0.008). Within the
      obese group, more A+/O+ children's asthma was well controlled with nedocromil
      than with budesonide (P = 0.022) or with placebo (P = 0.011). The PP algorithm
      performed significantly better (P < 0.001) than traditional machine learning
      algorithms for both short- and long-term asthma control prediction. Asthma
      control and bronchodilator response were the features most predictive of short
      term asthma control, regardless of type of controller medication or phenotype.
      Bronchodilator response and serum eosinophils were the most predictive features
      of asthma control, regardless of type of controller medication or phenotype.
      CONCLUSIONS: Advanced statistical machine learning approaches can be powerful
      tools for discovery of phenotypes based on treatment response and can aid in
      asthma control prediction in complex medical conditions such as asthma.

PMID- 29048951
TI  - Brief Commentary on the Article "Diagnostic Value of Plasma Pentraxin-3 in Acute
      Appendicitis".

PMID- 29048950
TI  - Integrating Population Heterogeneity Indices with Microfluidic Cell-Based Assays.
AB  - Recent advances in cell-based assays have involved the integration of single-cell
      analyses and microfluidics technology to facilitate both high-content and high
      throughput applications. These technical advances have yielded large datasets
      with single-cell resolution, and have given rise to the study of cell population
      dynamics, but statistical analyses of these populations and their properties have
      received much less attention, particularly for cells cultured in microfluidic
      systems. The objective of this study was to perform statistical analyses using
      Pittsburgh Heterogeneity Indices (PHIs) to understand the heterogeneity and
      evolution of cell population demographics on datasets generated from a
      microfluidic single-cell-resolution cell-based assay. We applied PHIs to cell
      population data obtained from studies involving drug response and soluble factor
      signaling of multiple myeloma cancer cells, and investigated effects of reducing
      population size in the microfluidic assay on both the PHIs and traditional
      population-averaged readouts. Results showed that PHIs are useful for examining
      changing population distributions within a microfluidic setting. Furthermore,
      PHIs provided data in support of finding the minimum population size for a
      microfluidic assay without altering the heterogeneity indices of the cell
      population. This work will be useful for novel assay development, and for
      advancing the integration of microfluidics, cell-based assays, and heterogeneity
      analyses.

PMID- 29048952
TI  - Increasing availability of illicit and prescription opioids among people who
      inject drugs in a Canadian setting, 2010-2014.
AB  - BACKGROUND: Nonmedical use of prescription opioid and illicit opioid has been
      increasing at an alarming rate in North America over the past decade. OBJECTIVE:
      We sought to examine the temporal trends and correlates of the availability of
      illicit and prescription opioids among people who inject drugs (PWID) in
      Vancouver, Canada. METHODS: Data were derived from three prospective cohort
      studies of PWID in Vancouver between 2010 and 2014. In semiannual interviews,
      participants reported the availability of five sets of illicit and prescription
      opioids: (1) heroin; (2) Percocet (oxycodone/acetaminophen), Vicodin
      (hydrocodone/acetaminophen), or Demerol (meperidine); (3) Dilaudid
      (hydromorphone); (4) Morphine; (5) oxycontin/OxyNEO (controlled-release
      oxycodone). We defined perceived availability as immediate (e.g., available
      within 10 minutes) versus no availability/available after 10 minutes. The trend
      and correlation of immediate availability were identified by multivariable
      generalized estimating equations logistic regression. RESULTS: Among 1584
      participants, of which 564 (35.6%) were female, the immediate availability of all
      illicit and prescribed opioids (except for oxycontin/OxyNEO) increased over time,
      independent of potential confounders. The Adjusted Odds Ratios of immediate
      availability associated with every calendar year increase were between 1.09 (95%
      confidence interval 1.05-1.12) (morphine and Dilaudid) and 1.13 (95% confidence
      interval 1.09-1.17) (Percocet/Vicodin/Demerol) (all p-values <0.05). CONCLUSION:
      The availability of most prescription opioids had continued to increase in recent
      years among our sample of PWID in Vancouver. Concurrent increases in the
      availability of heroin were also observed, raising concerns regarding combination
      of both illicit and prescription opioid use among PWID that could potentially
      increase the risk of overdose.

PMID- 29048953
TI  - Community Health Workers in the United States: Challenges in Identifying,
      Surveying, and Supporting the Workforce.
AB  - Community health workers (CHWs) are members of a growing profession in the United
      States. Studying this dynamic labor force is challenging, in part because its
      members have more than 100 different job titles. The demand for timely, accurate
      information about CHWs is increasing as the profession gains recognition for its
      ability to improve health outcomes and reduce costs. Although numerous surveys of
      CHWs have been conducted, the field lacks well-delineated methods for gaining
      access to this hard-to-identify workforce. We outline methods for surveying CHWs
      and promising approaches to engage the workforce and other stakeholders in
      conducting local, state, and national studies. We also highlight successful
      strategies to overcome challenges in CHW surveys and future directions for
      surveying the field.

PMID- 29048954
TI  - The Cumulative Probability of Arrest by Age 28 Years in the United States by
      Disability Status, Race/Ethnicity, and Gender.
AB  - OBJECTIVES: To estimate the cumulative probability (c) of arrest by age 28 years
      in the United States by disability status, race/ethnicity, and gender. METHODS: I
      estimated cumulative probabilities through birth cohort life tables with data
      from the National Longitudinal Survey of Youth, 1997. RESULTS: Estimates
      demonstrated that those with disabilities have a higher cumulative probability of
      arrest (c = 42.65) than those without (c = 29.68). The risk was
      disproportionately spread across races/ethnicities, with Blacks with disabilities
      experiencing the highest cumulative probability of arrest (c = 55.17) and Whites
      without disabilities experiencing the lowest (c = 27.55). Racial/ethnic
      differences existed by gender as well. There was a similar distribution of
      disability types across race/ethnicity, suggesting that the racial/ethnic
      differences in arrest may stem from racial/ethnic inequalities as opposed to
      differential distribution of disability types. CONCLUSIONS: The experience of
      arrest for those with disabilities was higher than expected. Police officers
      should understand how disabilities may affect compliance and other behaviors, and
      likewise how implicit bias and structural racism may affect reactions and actions
      of officers and the systems they work within in ways that create inequities.

PMID- 29048955
TI  - Integrating HIV Preexposure Prophylaxis (PrEP) Into Routine Preventive Health
      Care to Avoid Exacerbating Disparities.
AB  - More than 3 decades since its emergence in the United States, HIV continues to
      spread and disproportionately affect socially marginalized groups. Preexposure
      prophylaxis (PrEP), a highly effective prevention strategy federally approved
      since 2012, could fundamentally alter the course of the epidemic. However, PrEP's
      potential has not been fully realized, in part because health care providers have
      been slow to adopt PrEP in clinical practice and have been selective in their
      discussion of PrEP with patients. This nonstandardized approach has constrained
      PrEP access. PrEP access has not only been inadequate but also inequitable, with
      several groups in high need showing lower rates of uptake than do their socially
      privileged counterparts. Recognizing these early warning signs that current
      approaches to PrEP implementation could exacerbate existing HIV disparities, we
      call on health professionals to integrate PrEP into routine preventive health
      care for adult patients-particularly in primary care, reproductive health, and
      behavioral health settings. Drawing on the empirical literature, we present 4
      arguments for why doing so would improve access and access equity, and we
      conclude that the benefits clearly outweigh the challenges.

PMID- 29048956
TI  - Geographic Distribution of Scorpion Exposures in the United States, 2010-2015.
AB  - OBJECTIVES: To determine the geographic distribution of scorpion envenomations in
      the United States by zip code, with particular attention to the neurotoxic
      Centruroides sculpturatus (Arizona bark scorpion), for which an antivenom is
      available. METHODS: We obtained scorpion exposure cases for 2010 to 2015 from the
      National Poison Data System. Using geographic information systems software, we
      mapped total exposures and incidence rates for 9 states that reported more than
      100 annual calls. We also mapped cases that reported fasciculations and nystagmus
      (unique to C. sculpturatus among native scorpions). RESULTS: The highest exposure
      incidences occurred in Phoenix (up to 677 per 100 000 population) and Tucson
      (584), both in Arizona. Elsewhere, high incidences were found in El Paso, Texas
      (213); Oklahoma City (209) and Tulsa (178), Oklahoma; and Las Vegas, Nevada
      (170). Fasciculations and nystagmus were reported in Arizona and southeastern
      Nevada, with small numbers in surrounding states, including Utah. CONCLUSIONS:
      Scorpion exposures occurred at baseline rates throughout many of the southern
      states, whereas several states reported effects indicative of Arizona bark
      scorpion envenomation. Public Health Implications. Public and health care
      provider education, as well as the stocking of antivenom, should be targeted
      based on these findings.

PMID- 29048957
TI  - Loaded Handgun Carrying Among US Adults, 2015.
AB  - OBJECTIVES: To determine the frequency of loaded handgun carrying among US adult
      handgun owners, characterize those who carry, and examine concealed carrying by
      state concealed carry laws. METHODS: Using a nationally representative survey of
      US adults in 2015, we asked handgun owners (n = 1444) about their past-30-day
      carrying behavior. RESULTS: Among surveyed handgun owners, 24% (95% confidence
      interval[CI] = 21%, 26%) carried loaded handguns monthly, of whom 35% (95% CI =
      29%, 41%) did so daily; 82% (95% CI = 77%, 86%) carried primarily for protection.
      The proportion of handgun owners who carried concealed loaded handguns in the
      past 30 days was 21% (95% CI = 12%, 35%) in unrestricted states, 25% (95% CI =
      21%, 29%) in shall issue-no discretion states, 20% (95% CI = 16%, 24%) in shall
      issue-limited discretion states, and 9% (95% CI = 6%, 15%) in may-issue states.
      CONCLUSIONS: We estimate that 9 million US adult handgun owners carry loaded
      handguns monthly, 3 million do so every day, and most report protection as the
      main carrying reason. Proportionally fewer handgun owners carry concealed loaded
      handguns in states that allow issuing authorities substantial discretion in
      granting carrying permits.

PMID- 29048958
TI  - Shade Sails and Passive Recreation in Public Parks of Melbourne and Denver: A
      Randomized Intervention.
AB  - OBJECTIVES: To test whether shade sails will increase the use of passive
      recreation areas (PRAs). METHODS: We conducted a stratified randomized pretest
      posttest controlled design study in Melbourne, Australia, and Denver, Colorado,
      in 2010 to 2014. We randomized a sample of 144 public parks with 2 PRAs in full
      sun in a 1:3 ratio to treatment or control. Shade sails were built at 1 PRA per
      treatment park. The outcome was any use of the study PRA (n = 576 pretest and n =
      576 posttest observations; 100% follow-up). RESULTS: Compared with control PRAs
      (adjusted probability of use: pretest = 0.14, posttest = 0.17), use of treatment
      PRAs (pretest = 0.10, posttest = 0.32) was higher at posttest (odds ratio [OR] =
      3.91; 95% confidence interval [CI] = 1.71, 8.94). Shade increased use of PRAs in
      Denver (control: pretest = 0.18, posttest = 0.19; treatment: pretest = 0.16,
      posttest = 0.47) more than Melbourne (control: pretest = 0.11, posttest = 0.14;
      shaded: pretest = 0.06, posttest = 0.19; OR = 2.98; 95% CI = 1.09, 8.14).
      CONCLUSIONS: Public investment in shade is warranted for skin cancer prevention
      and may be especially useful in the United States. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier NCT02971709.

PMID- 29048959
TI  - A Community-Level Sodium Reduction Intervention, Boston, 2013-2015.
AB  - OBJECTIVES: To evaluate a community-level sodium-reduction intervention in
      Boston, Massachusetts. Reducing sodium in the food offerings of community
      settings may help reduce hypertension disparities. METHODS: We examined changes
      in the proportion of prepackaged foods with greater than 200 milligrams of sodium
      in 7 hospitals, 8 YMCAs, 4 community health centers, and 2 organizations serving
      homeless populations. Research assistants documented prepackaged items in
      cafeterias, kiosks, and vending machines before and after the intervention (2013
      2015). We assessed intervention change via linear mixed models accounting for
      repeated observations. RESULTS: There were 161 access points at baseline (4347
      facings) and 171 (4996 facings) at follow-up. The percentage of prepackaged
      products with greater than 200 milligrams of sodium decreased from 29.0% at
      baseline to 21.5% at follow-up (P = .003). Changes were driven by improvements in
      hospital cafeterias and kiosks (P = .003). The percentage of products with
      greater than 200 milligrams of sodium in YMCA vending decreased 58% (from 27.2%
      to 11.5%; P = .017); other organizations had nonsignificant declines.
      CONCLUSIONS: We found modest reductions in the percentage of higher-sodium
      prepackaged products across community institutions. Community-level interventions
      may increase availability of lower-sodium products in the food supply.

PMID- 29048961
TI  - Publicly Funded Family Planning Under Unprecedented Attack.

PMID- 29048960
TI  - Twitter-Based Detection of Illegal Online Sale of Prescription Opioid.
AB  - OBJECTIVES: To deploy a methodology accurately identifying tweets marketing the
      illegal online sale of controlled substances. METHODS: We first collected tweets
      from the Twitter public application program interface stream filtered for
      prescription opioid keywords. We then used unsupervised machine learning
      (specifically, topic modeling) to identify topics associated with illegal online
      marketing and sales. Finally, we conducted Web forensic analyses to characterize
      different types of online vendors. We analyzed 619 937 tweets containing the
      keywords codeine, Percocet, fentanyl, Vicodin, Oxycontin, oxycodone, and
      hydrocodone over a 5-month period from June to November 2015. RESULTS: A total of
      1778 tweets (< 1%) were identified as marketing the sale of controlled substances
      online; 90% had imbedded hyperlinks, but only 46 were "live" at the time of the
      evaluation. Seven distinct URLs linked to Web sites marketing or illegally
      selling controlled substances online. CONCLUSIONS: Our methodology can identify
      illegal online sale of prescription opioids from large volumes of tweets. Our
      results indicate that controlled substances are trafficked online via different
      strategies and vendors. Public Health Implications. Our methodology can be used
      to identify illegal online sellers in criminal violation of the Ryan Haight
      Online Pharmacy Consumer Protection Act.

PMID- 29048962
TI  - Integrating HIV Surveillance and Field Services: Data Quality and Care Continuum
      in King County, Washington, 2010-2015.
AB  - OBJECTIVES: To assess how integration of HIV surveillance and field services
      might influence surveillance data and linkage to care metrics. METHODS: We used
      HIV surveillance and field services data from King County, Washington, to assess
      potential impact of misclassification of prior diagnoses on numbers of new
      diagnoses. The relationship between partner services and linkage to care was
      evaluated with multivariable log-binomial regression models. RESULTS: Of the 2842
      people who entered the King County HIV Surveillance System in 2010 to 2015, 52%
      were newly diagnosed, 41% had a confirmed prior diagnosis in another state, and
      7% had an unconfirmed prior diagnosis. Twelve percent of those classified as
      newly diagnosed for purposes of national HIV surveillance self-reported a prior
      HIV diagnosis that was unconfirmed. Partner services recipients were more likely
      than nonrecipients to link to care within 30 days (adjusted risk ratio [RR] =
      1.10; 95% confidence interval [CI] = 1.03, 1.18) and 90 days (adjusted RR = 1.07;
      95% CI = 1.01, 1.14) of diagnosis. CONCLUSIONS: Integration of HIV surveillance,
      partner services, and care linkage efforts may improve the accuracy of HIV
      surveillance data and facilitate timely linkage to care.

PMID- 29048963
TI  - A 21st-Century Public Health Approach to Abortion.
AB  - In the United States, groups advocating for and against abortion rights often
      deploy public health arguments to advance their positions. Recently, these
      arguments have evolved into state laws that use the government health department
      infrastructure to increase law enforcement and regulatory activities around
      abortion. Many major medical and public health associations oppose these new laws
      because they are not evidence-based and do not protect women's health. Yet state
      health departments have been defending these laws in court. We propose a 21st
      century public health approach to abortion based in an accepted public health
      framework. Specifically, we apply the Centers for Disease Control and
      Prevention's 10 Essential Public Health Services framework to abortion to
      describe how health departments should engage with abortion. With this public
      health framework as our guide, we argue that health departments should be
      facilitating women's ability to obtain an abortion in the state and county where
      they reside, researching barriers to abortion care in their states and counties,
      and promoting the use of a scientific evidence base in abortion-related laws,
      policies, regulations, and implementation of essential services.

PMID- 29048964
TI  - Easiness of Legal Access to Concealed Firearm Permits and Homicide Rates in the
      United States.
AB  - OBJECTIVES: To examine the relation of "shall-issue" laws, in which permits must
      be issued if requisite criteria are met; "may-issue" laws, which give law
      enforcement officials wide discretion over whether to issue concealed firearm
      carry permits or not; and homicide rates. METHODS: We compared homicide rates in
      shall-issue and may-issue states and total, firearm, nonfirearm, handgun, and
      long-gun homicide rates in all 50 states during the 25-year period of 1991 to
      2015. We included year and state fixed effects and numerous state-level factors
      in the analysis. RESULTS: Shall-issue laws were significantly associated with
      6.5% higher total homicide rates, 8.6% higher firearm homicide rates, and 10.6%
      higher handgun homicide rates, but were not significantly associated with long
      gun or nonfirearm homicide. CONCLUSIONS: Shall-issue laws are associated with
      significantly higher rates of total, firearm-related, and handgun-related
      homicide.

PMID- 29048965
TI  - The Effectiveness of HIV Prevention Interventions in Socioeconomically
      Disadvantaged Ethnic Minority Women: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Surveys in the United States and Europe have shown a plateau of new
      HIV cases, with certain regions and populations disproportionately affected by
      the disease. Ethnic minority women and socioeconomically disadvantaged groups are
      disproportionately affected by HIV. Previous reviews have focused on prevention
      interventions targeting ethnic minority men who have sex with men, have not
      accounted for socioeconomic status, or have included only interventions carried
      out in clinical settings. OBJECTIVES: To review and assess the effectiveness of
      HIV prevention interventions targeting socioeconomically disadvantaged ethnic
      minority women in member states of the Organisation for Economic Co-operation and
      Development (OECD). SEARCH METHODS: On March 31, 2014, we executed a search using
      a strategy designed for the MEDLINE (Ovid), CINAHL, Embase, Scopus, and Web of
      Knowledge databases. Additional searches were conducted through the Cochrane
      Library, CRD Databases, metaRegister of Controlled Trials, EURONHEED, CEA
      Registry, and the European Action Program for Health Inequities as well as in
      gray literature sources. No language or date restrictions were applied. SELECTION
      CRITERIA: We selected studies assessing the effectiveness of interventions to
      prevent HIV among ethnic minority women of low socioeconomic status in which at
      least 80% of participants were reported to belong to an ethnic minority group and
      to have a low income or be unemployed. We included only studies that were
      conducted in OECD member states and were randomized controlled trials or quasi
      experimental investigations with a comparison group. DATA COLLECTION AND
      ANALYSIS: A data extraction form was developed for the review and used to collect
      relevant information from each study. We summarized results both qualitatively
      and quantitatively. The main outcomes were categorized into 3 groups: improved
      knowledge regarding transmission of HIV, behavior changes related to HIV
      transmission, and reductions in the incidence of sexually transmitted infections
      (STIs). We then performed meta-analyses to assess the effectiveness of the
      prevention interventions in terms of the 3 outcome categories. MAIN RESULTS: A
      total of 43 interventions were included, and 31 were judged to be effective, 7
      were partially effective, and 5 were ineffective. The most frequently recurring
      characteristics of these interventions were cultural adaptation, a cognitive
      behavioral approach, the use of small groups and trained facilitators, and a
      program duration of between 1 and 6 weeks. Our meta-analyses showed that the
      interventions improved knowledge of HIV transmission (odds ratio [OR] = 0.59; 95%
      confidence interval [CI] = 0.43, 0.75), increased the frequency of condom use (OR
      = 1.60; 95% CI = 1.16, 2.19), and significantly reduced the risk of STI
      transmission by 41% (relative risk = 0.59; 95% CI = 0.46, 0.75). CONCLUSIONS: Our
      study demonstrates the feasibility and effectiveness of HIV prevention
      interventions targeting socioeconomically deprived ethnic minority women. Public
      Health Implications. This is one of the first studies to include a meta-analysis
      assessing reductions in STI incidence among at-risk women who have participated
      in HIV prevention programs. The fact that our meta-analyses showed a
      statistically significant reduction in STI transmission provides important
      evidence supporting the overall effectiveness of directing prevention programming
      toward this vulnerable population. For policymakers, this review demonstrates the
      feasibility of working with multiple intervention components while at the same
      time facilitating more effective interventions that take into account the
      principal outcome measures of knowledge, behavior change, and STI transmission
      rates. The review also underscores the need for additional research outside the
      United States on the effectiveness of prevention interventions in this vulnerable
      group.

PMID- 29048966
TI  - Text Messaging for Improving Antiretroviral Therapy Adherence: No Effects After 1
      Year in a Randomized Controlled Trial Among Adolescents and Young Adults.
AB  - OBJECTIVES: To assess the effectiveness of Short Message Service (SMS) reminder
      messages on antiretroviral and cotrimoxazole prophylaxis adherence among HIV
      positive youths as well as the relative effectiveness of SMS with and without a
      response option. METHODS: Eligible HIV-positive patients aged 15 to 22 years at 2
      HIV clinics in Kampala, Uganda, participated in a year-long parallel individual
      randomized controlled trial and were assigned in a 1-to-1-to-1 ratio to a weekly
      SMS message group, weekly SMS message with response option group, or a usual-care
      control group. RESULTS: We enrolled 332 participants. Electronically measured
      mean adherence was 67% in the control group, 64% in the 1-way SMS group (95%
      confidence interval [CI] = 0.77, 1.14), and 61% in the 2-way SMS group (95% CI =
      0.75, 1.12) in an intent-to-treat analysis. Results for secondary outcomes and
      complete-case analysis were similarly statistically insignificant across groups.
      CONCLUSIONS: Despite previous evidence that interventions using SMS reminders can
      promote antiretroviral therapy adherence, this study shows that they are not
      always effective in achieving behavior change. More research is needed to find
      out for whom, and under what conditions, they can be beneficial. TRIAL
      REGISTRATION: ClinicalTrials.gov identifier: NCT00830622.

PMID- 29048968
TI  - Vaccines and the Trump Administration-Reasons for Optimism Amid Uncertainty.

PMID- 29048967
TI  - New and Recurrent Concussions in High-School Athletes Before and After Traumatic
      Brain Injury Laws, 2005-2016.
AB  - OBJECTIVES: To examine the trends of new and recurrent sports-related concussions
      in high-school athletes before and after youth sports traumatic brain injury
      laws. METHODS: We used an interrupted time-series design and analyzed the
      concussion data (2005-2016) from High School Reporting Injury Online. We examined
      the trends of new or recurrent concussion rates among US representative high
      school athletes participating in 9 sports across prelaw, immediate-postlaw, and
      postlaw periods by using general linear models. We defined 1 athlete exposure as
      attending 1 competition or practice. RESULTS: We included a total of 8043
      reported concussions (88.7% new, 11.3% recurrent). The average annual concussion
      rate was 39.8 per 100 000 athlete exposures. We observed significantly increased
      trends of reported new and recurrent concussions from the prelaw, through
      immediate-postlaw, into the postlaw period. However, the recurrent concussion
      rate showed a significant decline 2.6 years after the laws went into effect.
      Football exhibited different trends compared with other boys' sports and girls'
      sports. CONCLUSIONS: Observed trends of increased concussion rates are likely
      attributable to increased identification and reporting. Additional research is
      needed to evaluate intended long-term impact of traumatic brain injury laws.

PMID- 29048969
TI  - School-Based Curriculum to Improve Depression Literacy Among US Secondary School
      Students: A Randomized Effectiveness Trial.
AB  - OBJECTIVES: To determine the effectiveness of a universal school-based depression
      education program. METHODS: In 2012-2015, we matched 6679 students from 66
      secondary schools into pairs by state (Maryland, Delaware, Pennsylvania,
      Michigan, and Oklahoma) and randomized to the Adolescent Depression Awareness
      Program (ADAP; n = 3681) or to a waitlist control condition (n = 2998). Trained
      teachers delivered ADAP as part of the health education curriculum to students
      aged 14 to 15 years. The primary outcome was depression literacy. Secondary
      outcomes included mental health stigma and, in a subset of the sample, the
      receipt of mental health services. Follow-up was at 4 months. RESULTS: ADAP
      resulted in significantly higher levels of depression literacy among
      participating students than did waitlist controls, after adjusting for pretest
      assessment depression literacy (P < .001). Overall, ADAP did not significantly
      affect stigma (P = .1). After ADAP, students approached 46% of teachers with
      concerns about themselves or others. Of students who reported the need for
      depression treatment, 44% received treatment within 4 months of ADAP
      implementation. CONCLUSIONS: ADAP is an effective public health intervention for
      improving depression literacy among students. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02099305.

PMID- 29048970
TI  - Population Group Abortion Rates and Lifetime Incidence of Abortion: United
      States, 2008-2014.
AB  - OBJECTIVES: To assess the prevalence of abortion among population groups and
      changes in rates between 2008 and 2014. METHODS: We used secondary data from the
      Abortion Patient Survey, the American Community Survey, and the National Survey
      of Family Growth to estimate abortion rates. We used information from the
      Abortion Patient Survey to estimate the lifetime incidence of abortion. RESULTS:
      Between 2008 and 2014, the abortion rate declined 25%, from 19.4 to 14.6 per 1000
      women aged 15 to 44 years. The abortion rate for adolescents aged 15 to 19 years
      declined 46%, the largest of any group. Abortion rates declined for all racial
      and ethnic groups but were larger for non-White women than for non-Hispanic White
      women. Although the abortion rate decreased 26% for women with incomes less than
      100% of the federal poverty level, this population had the highest abortion rate
      of all the groups examined: 36.6. If the 2014 age-specific abortion rates
      prevail, 24% of women aged 15 to 44 years in that year will have an abortion by
      age 45 years. CONCLUSIONS: The decline in abortion was not uniform across all
      population groups.

PMID- 29048971
TI  - Protocol for Efficient Generation and Characterization of Adeno-Associated Viral
      Vectors.
AB  - Adeno-associated virus vectors are a powerful tool for gene transfer approaches.
      We have established a simple and fast plasmid-based production system for
      achieving high adeno-associated virus titers within 6 working days. The same
      procedure can be used for all serotypes and thus allows direct comparability of
      different serotypes. In this protocol we describe a step-by-step procedure that
      results in well-characterized vectors suitable for both in vitro approaches and
      preclinical studies.

PMID- 29048973
TI  - Safety and Efficacy Implications of Discontinuing Combination Ipilimumab and
      Nivolumab in Advanced Melanoma.

PMID- 29048972
TI  - New Persistent Opioid Use Among Patients With Cancer After Curative-Intent
      Surgery.
AB  - Purpose The current epidemic of prescription opioid misuse has increased scrutiny
      of postoperative opioid prescribing. Some 6% to 8% of opioid-naive patients
      undergoing noncancer procedures develop new persistent opioid use; however, it is
      unknown if a similar risk applies to patients with cancer. We sought to define
      the risk of new persistent opioid use after curative-intent surgery, identify
      risk factors, and describe changes in daily opioid dose over time after surgery.
      Methods Using a national data set of insurance claims, we identified patients
      with cancer undergoing curative-intent surgery from 2010 to 2014. We included
      melanoma, breast, colorectal, lung, esophageal, and hepato-pancreato
      biliary/gastric cancer. Primary outcomes were new persistent opioid use (opioid
      naive patients who continued filling opioid prescriptions 90 to 180 days after
      surgery) and daily opioid dose (evaluated monthly during the year after surgery).
      Logistic regression was used to identify risk factors for new persistent opioid
      use. Results A total of 68,463 eligible patients underwent curative-intent
      surgery and filled opioid prescriptions. Among opioid-naive patients, the risk of
      new persistent opioid use was 10.4% (95% CI, 10.1% to 10.7%). One year after
      surgery, these patients continued filling prescriptions with daily doses similar
      to chronic opioid users ( P = .05), equivalent to six tablets per day of 5-mg
      hydrocodone. Those receiving adjuvant chemotherapy had modestly higher doses ( P
      = .002), but patients with no chemotherapy still had doses equivalent to five
      tablets per day of 5-mg hydrocodone. Across different procedures, the covariate
      adjusted risk of new persistent opioid use in patients receiving adjuvant
      chemotherapy was 15% to 21%, compared with 7% to 11% for those with no
      chemotherapy. Conclusion New persistent opioid use is a common iatrogenic
      complication in patients with cancer undergoing curative-intent surgery. This
      problem requires changes to prescribing guidelines and patient counseling during
      the surveillance and survivorship phases of care.

PMID- 29048974
TI  - Strengthening the working alliance through a clinician's familiarity with the 12
      step approach.
AB  - BACKGROUND: The working alliance plays an important role in the substance use
      disorder treatment process. Many substance use disorder treatment providers
      incorporate the 12-Step approach to recovery into treatment. With the 12-Step
      approach known among many clients and clinicians, it may well factor into the
      therapeutic relationship. OBJECTIVE: We investigated how, from the perspective of
      clients, a clinician's level of familiarity with and in-session time spent on the
      12-Step approach might affect the working alliance between clients and
      clinicians, including possible differences based on a clinician's recovery
      status. METHOD: We conducted a secondary study using data from 180 clients and 31
      clinicians. Approximately 81% of client participants were male, and approximately
      65% of clinician participants were female. We analyzed data with Stata using a
      population-averaged model. RESULTS: From the perspective of clients with a
      substance use disorder, clinicians' familiarity with the 12-Step approach has a
      positive relationship with the working alliance. The client-estimated amount of
      in-session time spent on the 12-Step approach did not have a statistically
      significant effect on ratings of the working alliance. A clinician's recovery
      status did not moderate the relationship between 12-Step familiarity and the
      working alliance. CONCLUSION: These results suggest that clinicians can
      influence, in part, how their clients perceive the working alliance by being
      familiar with the 12-Step approach. This might be particularly salient for
      clinicians who provide substance use disorder treatment at agencies that
      incorporate, on some level, the 12-Step approach to recovery.

PMID- 29048976
TI  - Healthy Out-Group Members Are Represented Psychologically as Infected In-Group
      Members.
AB  - A range of studies have demonstrated that people implicitly treat out-groups as
      the carriers of pathogens and that considerable prejudice against out-groups is
      driven by concerns about pathogens. Yet the psychological categories that are
      involved and the selection pressures that underlie these categories remain
      unclear. A common view is that human pathogen-avoidance psychology is
      specifically adapted to avoid out-groups because of their potentially different
      pathogens. However, the series of studies reported here shows that there is no
      dedicated category for reasoning about out-groups in terms of pathogens.
      Specifically, a memory-confusion experiment conducted with two large-scale
      samples of Americans (one nationally representative) yielded strong, replicable
      evidence that healthy out-group members are represented using the same
      psychological category that is used to represent manifestly infected in-group
      members. This suggests that the link between out-group prejudice and pathogen
      concerns is a by-product of general mechanisms for treating any unfamiliar
      appearance as an infection cue.

PMID- 29048975
TI  - Addressing barriers to vaccine acceptance: an overview.
AB  - Addressing the drivers of vaccine hesitancy and the barriers to vaccine
      acceptance is a complex but important task. While the percentage of hesitant does
      vary from country to country and in time few, if any, countries are ever free
      from this problem. Overcoming hesitancy requires detection, diagnosis and
      tailored intervention as there is no simple strategy that can address all of the
      barriers to vaccine acceptance. Immunization program managers and health care
      workers need to become adept at recognizing and tackling hesitancy in all of its
      incarnations if high levels of vaccine acceptance are to be achieved but must
      also actively support immunization acceptors in order to build and support
      vaccine acceptance resiliency. This paper presents evidence-informed strategies
      to achieve these goals.

PMID- 29048977
TI  - Off-Clamp Robot-Assisted Partial Nephrectomy: How Far Shall We Proceed?
AB  - BACKGROUND: Off-clamp robot-assisted partial nephrectomy (RAPN) is associated
      with increased intraoperative blood loss compared with on-clamp technique. Our
      aim was to demonstrate our surgical technique and to determine which tumors are
      ideally suited for this technique. METHODS: Sixty-two patients who underwent off
      clamp RAPN for renal tumor between 2006 and 2016 were retrospectively analyzed.
      Increased estimated blood loss (EBL) volume was defined as more than 75
      percentile. receiver operating characteristic (ROC) analysis was used to
      determine exact cut-off tumor size and the preoperative aspects and dimensions
      used for an anatomical (PADUA) score that are associated with increased EBL. Risk
      factors for increased EBL >400 mL and chronic kidney disease (CKD) upstaging were
      evaluated using logistic regression analysis. RESULTS: The median follow-up
      period was 20 months (interquartile range [IQR]: 12-84). Patient's mean age, mean
      tumor size, and mean body mass index were 53.5 +/- 12.2 years, 2.6 +/- 1.5 cm,
      and 25 +/- 4.1 kg/m2, respectively. Median EBL volume was 200 mL (IQR: 100-400).
      ROC analysis showed that tumor size of 3.2 cm (area under the curve [AUC] = 0.82,
      P < .001) and PADUA score of 9 (AUC = 0.79, P = .001) were cut-off values for
      increased EBL >400 mL. Patients with tumor size >3.2 cm had longer operative time
      (116 versus 163 minutes, P = .002), more EBL (150 versus 575 mL, P < .001), and
      higher blood transfusion rate (0% versus 18.8%, P = .015), with increased
      tendency of conversion to radical nephrectomy (0% versus 12.5%, P = .063)
      compared with tumor size <=3.2 cm. Overall CKD upstaging was present in 22
      patients (35.4%). Multivariable logistic regression analysis showed that EBL >400
      mL was the only predictor of CKD upstaging (odds ratio: 6.704, P = .009).
      CONCLUSIONS: Our study showed that the risk of intraoperative bleeding and
      transfusion rate during off-clamp RAPN is increased if tumor size >3.2 cm and/or
      PADUA complexity score >=9. Moreover, EBL >400 mL was a risk factor of CKD
      upstaging, despite zero ischemia. Further larger prospective studies are
      warranted to validate our results.

PMID- 29048978
TI  - Antitumor effect of oral cancer vaccine with Bifidobacterium delivering WT1
      protein to gut immune system is superior to WT1 peptide vaccine.
AB  - Despite the revolutionary progress of immune checkpoint inhibitors (CPIs) for
      cancer immunotherapy, CPIs are effective only in a subset of patients. Combining
      CPIs and cancer vaccines to achieve better clinical outcomes is a reasonable
      approach since CPI enhances cancer vaccine-induced tumor-associated antigen (TAA)
      specific CTL. Among the various TAAs so far identified, WT1 protein is one of the
      most promising TAAs as a cancer vaccine target. Until now clinical trials of WT1
      vaccine have demonstrated only modest clinical efficacy. These WT1 vaccines were
      based on peptides or dendritic cells (DCs), and there was no oral cancer vaccine.
      Recently, we developed a WT1 oral cancer vaccine using a recombinant
      Bifidobacterium displaying WT1 protein, which can efficiently deliver WT1 protein
      to the gut immune system, and we demonstrated that this oral cancer vaccine had a
      significant anti-tumor effect in a C1498-WT1 murine leukemia syngeneic tumor
      model. The WT1 protein displayed in this vaccine consists of about 70% of the WT1
      amino acid sequence including multiple known CD4 and CD8 T-cell epitopes of WT1.
      In this commentary, we introduce our recent data indicating the superior anti
      tumor effect of a WT1 oral cancer vaccine delivering WT1 protein to the gut
      immune system compared to a peptide vaccine.

PMID- 29048979
TI  - Comparison of Single-Port Percutaneous Extraperitoneal Repair and Three-Port Mini
      Laparoscopic Repair for Pediatric Inguinal Hernia.
AB  - AIM: Laparoscopy has been widely used in surgical practice in pediatric age, and
      many techniques for laparoscopic hernia repair have been described till now. In
      this study, we compared two laparoscopic techniques performed by two surgeons;
      each surgeon practicing only one of the two techniques. MATERIALS AND METHODS: A
      retrospective analysis was performed on the surgical charts, enrolling 71
      patients with uncomplicated inguinal hernia. Patients were divided into two
      groups according to the type of surgery: (Group A, 24 patients aged 2 months-8
      years) laparoscopic percutaneous internal ring suturing technique and (Group B,
      47 patients aged 35 days-12 years) three-port mini-laparoscopic technique. The
      hernia sac was ligated at the level of internal ring, using nonabsorbable 4/0-3/0
      suture. Any unexpected contralateral opening was repaired in the same manner for
      both groups. Follow-up period was 4 months-2 years and 9 months-8 years,
      respectively. Operative time and complications were analyzed. RESULTS: Operation
      time (19.58 +/- 7.06 minutes versus 35.87 +/- 10.34 minutes, P < .001) was
      shorter in the percutaneous repair group. However, when subdivided by unilateral
      and bilateral presentation, only unilateral operative time was shorter compared
      to three-port group. There were no recurrences in Group A, while two recurrences
      occurred in Group B during the learning curve period. A contralateral opening
      accompanied the presenting unilateral hernia in 3 cases for Group A and 16 for
      Group B. One patient had to be converted open resulting from epigastric vessel
      injury, and postop hydrocele formation was seen in another in Group A. No
      intraoperative complications were seen in Group B. CONCLUSION: The overall
      experience shows that laparoscopic repair is a reliable approach regardless of
      the chosen technique. Percutaneous repair seems to be a less invasive method with
      shorter operative time, but it is not free of complications according to this
      series.

PMID- 29048980
TI  - The 2016 Lifetime Immunization Schedule, approved by the Italian scientific
      societies: A new paradigm to promote vaccination at all ages.
AB  - Medical scientific societies have the core mission of producing, pooling and
      disseminating solid and updated scientific information. We report the successful
      experience of the partnership of four national Medical Scientific Societies
      active in Italy in producing scientific advice on vaccines and vaccination. In
      particular, i) the Italian Society of Hygiene, Preventive Medicine and Public
      Health; SitI, ii) the Italian Society of Paediatrics; SIP, iii) the "Italian
      Federation of General Practitioners"; FIMP, and iv) the Italian Federation of
      General Medicine FIMMG) have worked together since 2012 to produce shared
      evidence-based recommendations on vaccination schedules, namely the "Lifetime
      Immunization Schedule" which introduced for the first time in Italy a life-course
      approach to vaccination. The 2014 edition of the "Lifetime Immunization Schedule"
      was used as a basis to develop the 2017-2019 Italian National Prevention Plan,
      approved by The Italian Ministry of Health in February 2017. In this report, we
      present the structure, content and supporting evidence of the new 2016 "Lifetime
      Immunization Schedule" and we expand on the influential role of medical
      scientific societies in researching and advocating for effective and safe
      vaccination programmes' implementation at the national level.

PMID- 29048981
TI  - Women and the Decision to Leave, Linger, or Lean In: Predictors of Intent to
      Leave and Aspirations to Leadership and Advancement in Academic Medicine.
AB  - BACKGROUND: The Association of American Medical Colleges reports continued low
      rates of female faculty as professors and in leadership positions. While
      attrition and discrimination have both been proposed as explanations, recent
      literature has suggested that women's professional motivations, ingrained
      behavior, and perceptions of organizational support may also play a role.
      METHODS: The authors employed a series of scales informed by the turnover theory
      (which predicts intent to leave an organization), previously validated and used
      in business and engineering studies, but rarely used in academic medicine. The
      authors proposed and tested a multiple regression model to assess predictors
      (role strain, work-life balance, and organizational climate) for three outcome
      variables: seeking promotion, seeking leadership, and intent to leave. RESULTS:
      Survey results from 614 faculty members indicated that gender significantly
      influenced both promotion and leadership seeking, but not intent to leave.
      Perceived work-family conflict was negatively correlated with leadership seeking
      for women, but not for men. Positive views of organizational support and
      commitment were associated with promotion seeking and persistence for all
      participants. Role strain was positively correlated with desire for promotion and
      leadership, as well as with intent to leave. CONCLUSIONS: Female faculty may not
      be leaning in to promotion and leadership roles because of increased role
      conflict, work-life concerns, and organizational factors; this seems to be more
      of a factor for female clinical rather than research faculty. Work-family
      conflict affects male and female faculty differently and should be addressed in
      efforts to retain faculty and to remove barriers for female faculty seeking
      leadership opportunities.

PMID- 29048982
TI  - Symptom Relief and Palliative Care during the Last Week of Life among Patients
      with Heart Failure: A National Register Study.
AB  - BACKGROUND: Heart failure is a disease with high morbidity, mortality, and
      physical and psychological burden. More knowledge about the care provided for
      patients with heart failure close to death is needed. OBJECTIVE: The aim was to
      describe key aspects of palliative care during the last week of life in patients
      with heart failure, as reported by healthcare professionals. DESIGN: This is a
      national register study. SETTING/SUBJECTS: The study included 3981 patients with
      diagnosed heart failure as the underlying cause of death. MEASUREMENTS: Data were
      obtained from the Swedish Register of Palliative Care, a national quality
      register that focuses on patients' last week of life, independent of diagnosis or
      care setting. The register includes information about care interventions
      connected with key aspects of palliative care. Data are reported retrospectively
      by a nurse or physician at the healthcare unit where the patient dies. RESULTS:
      Only 4.2% of patients with heart failure received specialized palliative care. In
      their last week of life, symptom prevalence was high, validated scales were
      seldom used, and symptoms were unsatisfactorily relieved. Around one-fifth (17%)
      of the patients in the study died alone. Less than half of family members had
      been offered bereavement support (45%). Moreover, one-third (28%) of the patients
      and more than half (61%) of the family members were reported to have had end-of
      life discussions with a physician during the illness trajectory. CONCLUSION: The
      results indicate inadequate palliative care for patients with heart failure
      during their last week of life.

PMID- 29048983
TI  - Representation of Women and Minorities in Clinical Trials for New Molecular
      Entities and Original Therapeutic Biologics Approved by FDA CDER from 2013 to
      2015.
AB  - BACKGROUND: The U.S. Food and Drug Administration (FDA) has made efforts to
      encourage adequate assessment of women, racial/ethnic minorities, and geriatric
      participants in clinical trials through regulations and guidance documents. This
      study surveyed the demographics of clinical trial participants and the presence
      of efficacy and safety analyses by sex for new drugs approved between 2013 and
      2015 by the FDA Center for Drug Evaluation and Research. METHODS: New drug
      marketing applications submitted to FDA were surveyed for demographic data (sex,
      race, ethnicity, and age) and the presence of sex-based analyses for efficacy and
      safety. The Ratio of the Proportion of women in clinical trials for the indicated
      disease population relative to the estimated Proportion of women in the disease
      population (PPR) was calculated for new drug indications. RESULTS: Of the 102 new
      drugs in this cohort (defined as new molecular entity drugs and original
      therapeutic biologics), sex was reported for >99.9% of trial participants, and
      women accounted for 40.4% of these participants. An estimated 77.2% of
      participants were White, 6.4% were Black/African American, and 29.1% were aged
      >=65 years. Sex-based analyses for both efficacy and safety were conducted for
      93.1% of applications. PPR was calculated for 82 new drugs for a total of 60
      indications, of which 50 indications (83.3%) had a PPR >=0.80. CONCLUSIONS: Sex
      data are now collected for almost all study participants, and this study shows
      appropriate sex participation for most new drugs when estimated disease
      prevalence by sex (PPR) is considered. Therapeutic area and disease indication
      are important considerations when assessing the sex of participants because
      variation occurs depending on the disease under study. Some racial minorities,
      especially Blacks/African Americans, are still not well represented in most drug
      development programs and remain an area where improvement is needed.

PMID- 29048984
TI  - Development of Middle East Respiratory Syndrome Coronavirus vaccines - advances
      and challenges.
AB  - Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is an emerging pathogen
      with the potential to pose a threat to global public health. Sporadic cases and
      outbreaks continue to be reported in the Middle East, and case fatality rates
      remain high at approximately 36% globally. No specific preventive or therapeutic
      countermeasures currently exist. A safe and effective vaccine could play an
      important role in protecting against the threat from MERS-CoV. This review
      discusses human vaccine candidates currently under development, and explores
      viral characteristics, molecular epidemiology and immunology relevant to MERS-CoV
      vaccine development. At present, a DNA vaccine candidate has begun a human
      clinical trial, while two vector-based candidates will very soon begin human
      trials. Protein-based vaccines are still at pre-clinical stage. Challenges to
      successful development include incomplete understanding of viral transmission,
      pathogenesis and immune response (in particular at the mucosal level), no optimal
      animal challenge models, lack of standardized immunological assays, and
      insufficient sustainable funding.

PMID- 29048985
TI  - Impact of meningococcal group B OMV vaccines, beyond their brief.
AB  - Meningococcal group B outer membrane vesicle vaccines have been used widely in
      Cuba, New Zealand, and Brazil. They are immunogenic and initially assessed
      largely by their ability to induce serum bactericidal activity. Measures of
      efficacy indicate good protection against homologous strains in older children
      and adults. Effectiveness appears broader than predicted by immunogenicity and
      efficacy studies. The recent discovery that meningococcal group B OMVs may
      protect against the related Neisseria species N.gonorrhoeae suggests more to
      these interesting antigen collections than meets the eye. Currently there are two
      OMV-containing group B vaccines available, the new recombinant protein-based
      Bexsero(r) developed by Novartis and VA-MENGOC-BC(r) developed by the Finlay
      institute in Cuba. Also, a third group B vaccine based on two recombinant factor
      H binding proteins (Trumenba(r), Pfizer), has recently been licenced but it does
      not include OMV. This commentary explores the population impact that group B OMV
      vaccines have had on meningococcal and gonorrhoea diseases. Given the
      heterologous effect against diverse strains of the meningococcus observed in
      older children and adults, and recent evidence to suggest moderate protection
      against gonorrhoea, there may be a role for these vaccines in programmes
      targeting adolescents and groups high at risk for both meningococcal disease and
      gonorrhoea.

PMID- 29048986
TI  - Laparoscopic Versus Open Surgery Still an Open Debate.
AB  - Many would think that today minimally invasive surgery is the standard of care in
      the United States and that the conventional "open" approach would be relegated to
      few complex procedures or difficult redo operations. However, a great variability
      still exists in the utilization of laparoscopic surgery in the United States.
      This variability in surgical care of common diseases raises important ethical and
      economic issues and warrants a serious look by healthcare providers, insurance
      companies, and patients.

PMID- 29048987
TI  - Health literacy and vaccination: A systematic review.
AB  - This systematic review describes the current relationship between health literacy
      (HL) and vaccination (including attitude to vaccines, intention to vaccinate, and
      vaccine uptake). The aim is to comprehend the role of HL as a determinant of
      vaccine hesitancy. For this purpose, the following databases were explored from 1
      January 2007 to 15 January 2017: PubMed, Embase, PsycINFO, ERIC, Health Evidence,
      Centre for Reviews and Dissemination, Scopus, Web of Science, and Cochrane
      Library. Nine studies were included in the final synthesis. The role of HL in
      predicting vaccine hesitancy or acceptance seems to be influenced by a few key
      factors. These include country, age, and type of vaccine. However, the
      relationship between HL and vaccination remains unclear. New research studies are
      needed-particularly longitudinal ones that use multiple measurement tools. This
      would facilitate a better understanding of the role of HL in predicting vaccine
      uptake.

PMID- 29048988
TI  - Developmental strategy for a new Group A meningococcal conjugate vaccine
      (MenAfriVacR).
AB  - Until recently, periodic Group A meningococcal meningitis outbreaks were a major
      public health problem in the sub-Saharan Africa. In 2001, the Meningitis Vaccine
      Project (MVP), a partnership between the World Health Organization (WHO) and
      PATH, a Seattle-based NGO, and the Serum Institute of India Pvt Ltd (SIIPL)
      initiated discussions aimed at establishing a collaboration to develop a Group A
      meningococcal conjugate vaccine for this unmet medical need. Over the next 8
      years the partnership made countless strategic decisions about product
      characteristics, raw materials, potential target populations, geographic
      prioritization and affordability of the vaccine to name a few. These decisions
      evolved into detailed plans for preclinical development, extensive field trials
      in Africa and India and a focused regulatory strategy specific for the Men A
      conjugate vaccine. Important characteristics of the process included,
      flexibility, transparency andeffective partnerships that included public agencies
      as well as private companies in Africa, Europe, the United States and India.

PMID- 29048989
TI  - Vaccination in pregnancy: Attitudes of nurses, midwives and health visitors in
      England.
AB  - OBJECTIVE: To examine amongst healthcare professionals in England; knowledge of
      vaccinations in pregnancy, their perceived roles in these programmes and whether
      they recommend scheduled vaccines to pregnant women. DESIGN: Cross sectional
      survey (online questionnaire) Setting: Healthcare workers in contact with
      pregnant women in England. PARTICIPANTS: The survey analysis included 3441
      healthcare workers who had been surveyed during May to August 2015. The
      participants were midwives, practice nurses and health visitors, working in
      England who were members of the Royal College of Midwives, Royal College of
      Nursing and the Institute of Health Visiting. RESULTS: We found that knowledge of
      vaccination in pregnancy was high in all professional groups. Seventy three
      percent of all respondents would recommend the influenza vaccine and 74% would
      recommend the pertussis vaccine to pregnant women. They were more likely to
      recommend vaccination in pregnancy if they would personally have the influenza
      and pertussis vaccines themselves and/or if they had the influenza vaccine as a
      healthcare worker. Practice nurses were significantly more likely to recommend
      the pertussis and influenza vaccines to pregnant women than midwives and health
      visitors. Health professionals who had received immunisation training were more
      confident in giving advice to pregnant women. CONCLUSION: Immunisation training
      is essential if healthcare workers are to be informed and confident in
      effectively delivering the maternal immunisation programme and thus improving
      uptake of vaccines in pregnancy. These findings are important in tailoring
      educational programmes and addressing the training needs of different healthcare
      professional groups.

PMID- 29048990
TI  - Site-specific glycosylation profile of influenza A (H1N1) hemagglutinin through
      tandem mass spectrometry.
AB  - The study of influenza virus evolution in humans has revealed a significant role
      of glycosylation profile alterations in the viral glycoproteins - hemagglutinin
      (HA) and neuraminidase (NA), in the emergence of both seasonal and pandemic
      strains. Viral antigenic drift can modify the number and location of
      glycosylation sites, altering a wide range of biological activities and the
      antigenic properties of the strain. In view of the key role of glycans in
      determining antigenicity, elucidating the glycosylation profiles of influenza
      strains is a requirement towards the development of improved vaccines. Sequence
      based analysis of viral RNA has provided great insight into the role of glycosite
      modifications in altering virulence and pathogenicity. Nonetheless, this sequence
      based approach can only predict potential glycosylation sites. Due to
      experimental challenges, experimental confirmation of the occupation of predicted
      glycosylation sites has only been carried out for a few strains. Herein, we
      utilized HCD/CID-MS/MS tandem mass spectrometry to characterize the site-specific
      profile of HA of an egg-grown H1N1 reference strain (A/New Caledonia/20/1999). We
      confirmed experimentally the occupancy of glycosylation sites identified by
      primary sequence analysis and determined the heterogeneity of glycan structures.
      Four glycosylation sequons on the stalk region (N28, N40, N304 and N498) and four
      on the globular head (N71, N104, N142 and N177) of the protein are occupied. Our
      results revealed a broad glycan microheterogeneity, i.e., a great diversity of
      glycan compositions present on each glycosite. The present methodology can be
      applied to characterize other viruses, particularly different influenza strains,
      to better understand the impact of glycosylation on biological activities and aid
      the improvement of influenza vaccines.

PMID- 29048991
TI  - Impacts of Early Guideline-Directed 21-Gene Recurrence Score Testing on Adjuvant
      Therapy Decision Making.
AB  - PURPOSE: The 21-gene recurrence score (RS) assay is used to help formulate
      adjuvant chemotherapy recommendations for patients with estrogen receptor
      positive, early-stage breast cancer. Most frequently, medical oncologists order
      RS after surgery. Results take an additional 2 weeks to return, which can delay
      decision making. We conducted a prospective quality-improvement project to assess
      the impact of early guideline-directed RS ordering by surgeons before the first
      visit with a medical oncologist on adjuvant therapy decision making. MATERIALS
      AND METHODS: Surgical oncologists ordered RS testing following National
      Comprehensive Cancer Network guidelines at time of diagnosis or at time of
      surgery between July 1, 2015 and December 31, 2015. We measured the testing rate
      of patients eligible for RS, time to chemotherapy decisions, rates of
      chemotherapy use, accrual to RS-based clinical trials, cost, and physician
      acceptance of the policy and compared the results to patients who met eligibility
      criteria for early guideline-directed testing during the 6 months before the
      project. RESULTS: Ninety patients met eligibility criteria during the testing
      period. RS was ordered for 91% of patients in the early testing group compared
      with 76% of historical controls ( P < .001). Median time to chemotherapy decision
      was significantly shorter in the early testing group (20 days; 95% CI, 17 to 23
      days) compared with historical controls (32 days; 95% CI, 29 to 35 days; P <
      .001). There were no significant differences in time to chemotherapy initiation,
      chemotherapy use, RS-based trial enrollment, or calculated costs between the
      groups. CONCLUSION: Early guideline-directed RS testing in selected patients is
      an effective way to shorten time to treatment decisions.

PMID- 29048992
TI  - Eurasian Red Squirrels Show Little Seasonal Variation in Metabolism in Food
      Enriched Habitat.
AB  - Energy expenditure and ambient temperature (Ta) are intrinsically linked through
      changes in an animal's metabolic rate. While the nature of this relationship is
      stable, the breadth of change in thermoregulatory cost varies with body size and
      physiological acclimatization to season. To explore seasonal metabolic changes of
      small mammals, we studied a population of Eurasian red squirrels (Sciurus
      vulgaris) in a seminatural environment with a year-round supply of natural and
      supplemented food. In each season we measured the metabolic rate of wild-caught
      red squirrels, using open-flow respirometry, and hypothesized that individuals
      would make adjustments to contend with seasonal weather conditions. In comparison
      to summer animals, we predicted that winter squirrels would show (1) an increase
      in metabolic rate within the thermoneutral zone, (2) a decrease in the lower
      critical temperature of the thermoneutral zone, (3) a shallower slope of resting
      metabolic rate with decreasing Ta, and (4) lower thermal conductance.
      Surprisingly, we observed only minor changes in resting metabolic rate, and
      energetic modeling suggested that the scope of change was unlikely to be of
      ecological consequence. Hair area density was higher in winter than in summer,
      corresponding to a slightly elevated thermal conductance in summer, while body
      mass was reasonably constant year-round. We conclude that the scope of
      physiological seasonal adaptation is minimal when food is abundant and that
      squirrels instead rely on adjustments in activity to reduce exposure to low Ta.
      We suggest that this may explain the squirrel's success in a wide range of
      habitats, including urban areas, which require a rapid and flexible response to
      environmental changes and may indicate the capacity of other small mammal species
      to cope with environmental disturbance.

PMID- 29048993
TI  - Personalized Risk Prediction in Clinical Oncology Research: Applications and
      Practical Issues Using Survival Trees and Random Forests.
AB  - A crucial component of making individualized treatment decisions is to accurately
      predict each patient's disease risk. In clinical oncology, disease risks are
      often measured through time-to-event data, such as overall survival and
      progression/recurrence-free survival, and are often subject to censoring. Risk
      prediction models based on recursive partitioning methods are becoming
      increasingly popular largely due to their ability to handle nonlinear
      relationships, higher-order interactions, and/or high-dimensional covariates. The
      most popular recursive partitioning methods are versions of the Classification
      and Regression Tree (CART) algorithm, which builds a simple interpretable tree
      structured model. With the aim of increasing prediction accuracy, the random
      forest algorithm averages multiple CART trees, creating a flexible risk
      prediction model. Risk prediction models used in clinical oncology commonly use
      both traditional demographic and tumor pathological factors as well as high
      dimensional genetic markers and treatment parameters from multimodality
      treatments. In this article, we describe the most commonly used extensions of the
      CART and random forest algorithms to right-censored outcomes. We focus on how
      they differ from the methods for noncensored outcomes, and how the different
      splitting rules and methods for cost-complexity pruning impact these algorithms.
      We demonstrate these algorithms by analyzing a randomized Phase III clinical
      trial of breast cancer. We also conduct Monte Carlo simulations to compare the
      prediction accuracy of survival forests with more commonly used regression models
      under various scenarios. These simulation studies aim to evaluate how sensitive
      the prediction accuracy is to the underlying model specifications, the choice of
      tuning parameters, and the degrees of missing covariates.

PMID- 29048995
TI  - Computational revelation of binding mechanisms of inhibitors to endocellular
      protein tyrosine phosphatase 1B using molecular dynamics simulations.
AB  - Endocellular protein tyrosine phosphatase 1B (PTP1B) is one of the most promising
      target for designing and developing drugs to cure type-II diabetes and obesity.
      Molecular dynamics (MD) simulations combined with molecular mechanics generalized
      Born surface area (MM-GBSA) and solvated interaction energy methods were applied
      to study binding differences of three inhibitors (ID: 901, 941, and 968) to
      PTP1B, the calculated results show that the inhibitor 901 has the strongest
      binding ability to PTP1B among the current inhibitors. Principal component (PC)
      analysis was also carried out to investigate the conformational change of PTP1B,
      and the results indicate that the associations of inhibitors with PTP1B generate
      a significant effect on the motion of the WPD-loop. Free energy decomposition
      method was applied to study the contributions of individual residues to inhibitor
      bindings, it is found that three inhibitors can generate hydrogen bonding
      interactions and hydrophobic interactions with different residues of PTP1B, which
      provide important forces for associations of inhibitors with PTP1B. This research
      is expected to give a meaningfully theoretical guidance to design and develop of
      effective drugs curing type-II diabetes and obesity.

PMID- 29048994
TI  - Awareness of and willingness to be vaccinated by human papillomavirus vaccine
      among junior middle school students in Jinan, China.
AB  - BACKGROUND: Willingness to be vaccinated with human papillomavirus (HPV) vaccine
      among junior middle school students in China is not well understood. We conducted
      a cross-sectional study to assess awareness of HPV and the HPV vaccine and
      explore the factors associated with willingness to be vaccinated. METHODS: First
      year students from two junior middle schools in Jinan, China were selected by
      cluster sampling on December 28, 2015, December 26, 2016, and January 11, 2017,
      and a self-administered questionnaire was used to collect information.
      Multivariate logistic regression was conducted to explore the factors associated
      with willingness to be vaccinated with the HPV vaccine. RESULTS: A total of 1021
      junior middle school students participated in this survey. Only 15.5% of them had
      heard of HPV and 18.9% of them had heard of the HPV vaccine. Students who were
      willing to take the HPV vaccine in the future accounted for 66.9%. Factors
      associated with the HPV vaccination were: urban junior middle school students
      (AOR: 1.51, 95% CI: 1.09-2.09), female students (AOR: 1.90, 95% CI: 1.36-2.66),
      students surveyed in 2015 (AOR: 1.69, 95% CI: 1.26-2.28), regarding
      menstruation/spermatorrhoea as a normal physiological phenomenon (AOR: 1.64, 95%
      CI: 1.14-2.36), believing vaccination is an important way to prevent diseases
      (AOR: 1.36, 95% CI: 1.01-1.83), believing that the first vaccination should be in
      infancy (AOR: 1.41, 95% CI: 1.04-1.92), believing that cervical cancer is a
      concern for themselves (AOR: 1.95, 95% CI: 1.28-2.97), and having heard of HPV
      (AOR: 1.84, 95% CI: 1.13-2.98). CONCLUSIONS: Awareness of HPV and the HPV vaccine
      among junior students was low, however willingness to be vaccinated was high.
      Education focusing on HPV-related knowledge in addition to sex education is
      needed to promote the coverage of the HPV vaccine.

PMID- 29048997
TI  - Surgical Site Infections after Inguinal Hernia Repairs Performed in Low and
      Middle Human Development Index Countries: A Systematic Review.
AB  - BACKGROUND: Inguinal hernias are a common disorder in low- and middle-human
      development index countries (LMHDICs). Poor access to surgical care and lack of
      patient awareness often lead to delayed presentations of incarcerated or
      strangulated hernias and their associated morbidities. There is a scarcity of
      data on the baseline incidence of surgical site infections (SSIs) after hernia
      repair procedures in LMHDICs. METHODS: We performed a systematic review of the
      literature describing the incidence and management of SSIs after inguinal hernia
      repair in LMHDICs. We conducted qualitative and quantitative analyses of
      manuscripts describing patients undergoing hernia repair to establish a baseline
      SSI rate for this procedure in these settings. RESULTS: Three hundred twenty
      three abstracts were identified after applying search criteria, and 31 were
      suitable for the quantitative analysis. The overall pooled SSI rate was 4.1
      infections/100 open hernia repairs (95% confidence interval [CI] 3.0-5.3
      infections/100 open repairs), which is consistent with infection rates from high
      human development index countries. A separate subgroup analysis of laparoscopic
      hernia repairs found a weighted pooled SSI rate of 0.4 infections/100
      laparoscopic repairs (95% CI 0-2.4 infections/100 laparoscopic repairs).
      CONCLUSIONS: As surgical access continues to expand in LMHDIC settings, it is
      imperative to monitor surgical outcomes and ensure that care is provided safely.
      Establishing a baseline SSI rate for inguinal hernia repairs offers a useful
      benchmark for future studies and surgical programs in these countries.

PMID- 29048996
TI  - Aberrant DNA methylation in radon and/or cigarette smoke-induced malignant
      transformation in BEAS-2B human lung cell line.
AB  - It is well known that cigarette smoking (CS) and/or radon (Rn) induce malignant
      transformation in lung cells. To investigate the mechanisms underlying lung
      carcinogenesis induced by CS, Rn; or Rn followed by CS using BEAS-2B cell line
      derived from human bronchial epithelial cells. BEAS-2B cells were exposed to
      either Rn (20,000 Bq/m3) for 30 min or CS (20%) for 10 min or Rn followed by CS
      for 40 min. Global and gene-specific DNA methylation modifications were measured
      by microarray and methylation-specific polymerase chain reaction. Cell cycle and
      apoptosis were determined by flow cytometry, while soft agar colony formation was
      conducted to assess the characteristics of malignant transformation. Data
      demonstrated global hypomethylation as well as gene-specific DNA methylation
      alterations in all treatment groups compared to unexposed control cells. In
      addition, Rn and CS produced DNA hypermethylation of protein tyrosine phosphatase
      receptor type M and ectodysplasin A2 receptor, two genes related to malignant
      transformation. In all treatment conditions, cell proliferation and survival of
      malignant cells was increased, while apoptosis was initially first passage
      elevated but decreased at passages 5-15. Our results indicate that aberrant DNA
      methylation plays an important role in Rn- and/or CS-induced malignant
      transformation. In addition, BEAS-2B cell line may be used as an in vitro model
      to investigate mechanisms underlying malignant transformation induced by ambient
      environmental contaminants.

PMID- 29048998
TI  - Transmission of Pseudoloma neurophilia in Laboratory Zebrafish (Danio rerio) When
      Using Mass Spawning Chambers and Recommendations for Chamber Disinfection.
AB  - Pseudoloma neurophilia, a microsporidium that primarily infects neural tissues,
      is a common pathogen in laboratory zebrafish. The risk of parasite transmission
      with different spawning apparatuses and the effectiveness of disinfection are
      unknown. In this study, we spawned uninfected zebrafish with P. neurophilia
      infected zebrafish in either 50 L mass spawning chambers (MSCs) or 1 L standard
      breeding tanks (BTs). Fish were spawned once or thrice, with and without chamber
      disinfection between uses, to evaluate risk of vertical and horizontal
      transmission. Six disinfection protocols were tested to determine which
      effectively eliminated residual spores. We demonstrated that three consecutive
      uses of an MSC significantly increased the risk of transmission to other fish
      when compared to the use of BTs or only one spawning event in an MSC (both p <
      0.0001). Vertical transmission was not detected with any method. Disinfection
      with ~100 ppm bleach soak (pH ~7.0), 75 ppm Wescodyne(r) soak, and 175 ppm
      Wescodyne Plus spray was 100% effective in eliminating spores from the MSCs.
      Disinfection of MSCs before spawning did not decrease P. neurophilia transmission
      when infected fish remained present in the breeding population. Researchers
      should avoid using endemically infected fish in MSCs to minimize transmission of
      pathogens within their colonies.

PMID- 29048999
TI  - Structural distortions due to missense mutations in human formylglycine
      generating enzyme leading to multiple sulfatase deficiency.
AB  - The major candidate for multiple sulfatase deficiency is a defective
      formylglycine-generating enzyme (FGE). Though adequately produced, mutations in
      FGE stall the activation of sulfatases and prevent their activity. Missense
      mutations, viz. E130D, S155P, A177P, W179S, C218Y, R224W, N259I, P266L, A279V,
      C336R, R345C, A348P, R349Q and R349W associated with multiple sulfatase
      deficiency are yet to be computationally studied. Aforementioned mutants were
      initially screened through ws-SNPs&GO3D program. Mutant R345C acquired the
      highest score, and hence was studied in detail. Discrete molecular dynamics
      explored structural distortions due to amino acid substitution. Therein,
      comparative analyses of wild type and mutant were carried out. Changes in
      structural contours were observed between wild type and mutant. Mutant had low
      conformational fluctuation, high atomic mobility and more compactness than wild
      type. Moreover, free energy landscape showed mutant to vary in terms of its
      conformational space as compared to wild type. Subsequently, wild type and mutant
      were subjected to single-model analyses. Mutant had lesser intra molecular
      interactions than wild type suggesting variations pertaining to its secondary
      structure. Furthermore, simulated thermal denaturation showed dissimilar pattern
      of hydrogen bond dilution. Effects of these variations were observed as changes
      in elements of secondary structure. Docking studies of mutant revealed less
      favourable binding energy towards its substrate as compared to wild type.
      Therefore, theoretical explanations for structural distortions of mutant R345C
      leading to multiple sulfatase deficiency were revealed. The protocol of the study
      could be useful to examine the effectiveness of pharmacological chaperones prior
      to experimental studies.

PMID- 29049000
TI  - Oral Nutrition as a Form of Pre-Operative Enhancement in Patients Undergoing
      Surgery for Colorectal Cancer: A Systematic Review.
AB  - BACKGROUND: Nutritional status has major impacts on the outcome of surgery, in
      particular in patients with cancer. The aim of this review was to assess the
      merit of oral pre-operative nutritional support as a part of prehabilitation in
      patients undergoing surgery for colorectal cancer. METHODS: A systematic
      literature search and meta-analysis was performed according to the Preferred
      Reporting of Systematic Reviews and Meta-Analyses (PRISMA) recommendations in
      order to review all trials investigating the effect of oral pre-operative
      nutritional support in patients undergoing colorectal surgery. The primary
      outcome was overall complication rate. Secondary outcomes were incision infection
      rate, anastomotic leakage rate, and length of hospital stay. RESULTS: Five
      randomized controlled trials and one controlled trial were included. The studies
      contained a total of 583 patients with an average age of 63 y (range 23-88 y), of
      whom 87% had colorectal cancer. Malnourishment rates ranged from 8%-68%. All
      investigators provided an oral protein supplement. Overall patient compliance
      rates ranged from 72%-100%. There was no significant reduction in the overall
      complication rate in the interventional groups (odds ratio 0.82; 95% confidence
      interval 0.52 - 1.25). CONCLUSION: Current studies are too heterogeneous to
      conclude that pre-operative oral nutritional support could enhance the condition
      of patients undergoing colorectal surgery. Patients at risk have a relatively
      lean body mass deficit (sarcopenia) rather than an absolute malnourished status.
      Compliance is an important element of prehabilitation. Targeting patients at
      risk, combining protein supplements with strength training, and defining
      standardized patient-related outcomes will be essential to obtain satisfactory
      results.

PMID- 29049001
TI  - Effects of melatonin on mechanisms involved in hypertension using human umbilical
      vein endothelial cells.
AB  - Changes in diurnal rhythmicity in blood pressure (BP) are associated with
      hypertension and consequent cardiovascular damage. The involvement of diurnal
      rhythmicity as a pathogenic factor in hypertension is not fully understood. Since
      the hormone melatonin (MLT) regulates circadian rhythm, it was also of interest
      to determine whether this hormone played a role in hypertension-related
      alterations in circadian rhythm. Thus the aim of this study was to examine the
      mechanisms underlying MLT-mediated antihypertension. Human umbilical vein
      endothelial cells were incubated with MLT under 25 kPa pressure to simulate
      hypertension. Vasoactive substances including endothelin (ET), angiotensin II
      (Ang II), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS) were
      measured using ELISA assays. Results showed that MLT produced a significant
      decrease in ET at 18 and 24 h and Ang II at 18 h after treatment. In contrast,
      MLT significantly elevated NO levels and eNOS activity at 6, 12, 18, and 24 h,
      indicating that these oxidant indicators may be more sensitive to MLT-induced
      actions. Gene chip analysis identified 121 upregulated and 214 downregulated
      genes at 6 h after MLT treatment, predominantly involved in DNA replication, cell
      cycle regulation, amino acid metabolism, and cell cycle pathway. At 18 h, 63
      upregulated and 94 downregulated genes involved in circadian entrainment, cGMP
      PKG signaling pathway involved in NO synthesis, as well as secretion of renin and
      insulin, which are associated with BP regulation. Data suggest that the circadian
      antihypertensive effects of MLT might be associated with decrease in ET and Ang
      II, accompanied by rise in NO and eNOS and that NO and eNOS appear to be early
      bioindicators of hormonal effect.

PMID- 29049002
TI  - Cost-effectiveness of the Haemophilus influenzae type b vaccine for infants in
      mainland China.
AB  - OBJECTIVE: The aims of this study were to estimate the cost-effectiveness of the
      Haemophilus influenzae type b (Hib) vaccine for the prevention of childhood
      pneumonia, meningitis and other vaccine-preventable diseases in mainland China
      from a societal perspective and to provide information about the addition of the
      Hib vaccine to Chinese immunization programs. METHODS: A decision tree and the
      Markov model were used to estimate the costs and effectiveness of the Hib vaccine
      versus no Hib vaccine for a birth cohort of 100,000 children in 2016. The disease
      burden was estimated from the literature, statistical yearbooks and field
      surveys. Vaccine costs were calculated from government reports and the United
      Nations International Children's Emergency Fund (UNICEF) website. The WHO cost
      effectiveness thresholds were used to evaluate the Hib vaccine intervention. A
      one-way sensitivity analysis and probabilistic sensitivity analysis were
      performed to evaluate the parameter uncertainties. RESULTS: Within the
      hypothetical cohort, under a vaccination coverage of 90%, the Hib vaccine could
      reduce 91.4% of Hib pneumonia and 88.3% of Hib meningitis; the Hib vaccine could
      also prevent 25 deaths, 24 meningitis sequelae cases and 9 hearing loss cases
      caused by Hib infection. From a societal perspective, the incremental cost
      effectiveness ratio (ICER) of the Hib vaccine compared with no vaccination was
      US$ 13,640.1 at the market price, which was less than 3 times the GDP per capita
      of China in 2016. The ICER of the Hib vaccine was US$ -59,122.9 at the UNICEF
      price, indicating a cost savings. The largest portion of the uncertainty in the
      result was caused by the annual incidence of all-cause pneumonia, proportion of
      pneumonia caused by Hi, vaccine costs per dose, annual incidence of Hib
      meningitis and costs per episode of meningitis. The models were robust
      considering parameter uncertainties. CONCLUSION: The Hib vaccine is a cost
      effective intervention among children in mainland China. The cost of Hib vaccine
      should be reduced, and it should be introduced into Chinese immunization
      programs.

PMID- 29049003
TI  - "Tau immunotherapy: Hopes and hindrances".
AB  - Alzheimer's disease (AD) is a progressive neurological disorder having two major
      pathological hallmarks: the extracellular senile plaques and intracellular
      neurofibrillary tangles composed of amyloid beta protein and hyperphosphorylated
      tau respectively. Removal of protein deposits from AD brains are the newer
      attempts for treating AD. The major developments in this direction have been the
      amyloid and tau based therapeutics. While senile plaque removal employing
      monoclonal antibodies (mAbs) restore brain function in mouse models of AD, tau
      has been recently introduced as the major neurodegenerative factor mediating
      neural cell death. So, several research groups have focused on tau therapy. So
      far, the outcome of tau immunotherapy has been promising and clearance of
      hyperphosphorylated tau has been shown to restore the brain function in animal
      models. But the point is which phosphorylated tau is the most critical form to be
      removed from the brain, especially because removal of physiologic tau can cause
      neurodegenerative consequence. Recently, we have shown that phosphorylated tau at
      Thr231 in the cis conformation is a very early driver of neurodegeneration and
      cis mAb treatment efficiently restores brain structure and function in TBI
      models. Because of efficient therapeutic effects in mice model of TBI and
      considering cis pT231-tau accumulation in AD brains, it could be a very good
      candidate for tau immunotherapy upon several tauopathy disorders including AD.

PMID- 29049004
TI  - Long-Term Outcomes of Transoral Incisionless Fundoplication in a High-Risk
      Pediatric Population.
AB  - INTRODUCTION: Laparoscopic Nissen fundoplication (LNF) is the standard for
      surgical treatment of gastroesophageal reflux disease (GERD), but postoperative
      complications and pain are common in patients with severe neurological impairment
      (NI) and those undergoing reoperative procedures. Transoral incisionless
      fundoplication (TIF) is an endoscopic alternative to treat GERD. Long-term
      results in pediatric populations are unknown. METHODS: Eleven patients who
      underwent TIF between January 2008 and September 2010 were included. A
      retrospective chart review was performed to evaluate long-term patient outcomes.
      Median follow-up was 5.6 years (range = 0.42-8.76 years). RESULTS: Average
      patient age was 16.5 +/- 5.1 years. Severe NI was present in 81.8% (9/11) of
      patients, and 63.6% (7/11) had undergone one or more prior fundoplication
      attempts. Overall, symptomatic reflux recurred or persisted in 54.5% (6/11) of
      patients. Recurrent symptoms were more common among those who had previous
      fundoplications than those who did not (71.4% [5/7] vs. 25% [1/4]). Four patients
      went on to require reoperation, including one laparoscopic Nissen and three
      disconnects. At last follow-up, 81.8% (9/11) of patients were still on antireflux
      medications. CONCLUSIONS: This is the first report of long-term outcomes for
      treatment of GERD using TIF in a pediatric population. The recurrence rate was
      high, likely related to the fact that the population treated was extremely high
      risk. Recurrence was higher in patients with a prior fundoplication, perhaps
      identifying prior antireflux operations as a relative contraindication to TIF.
      Nevertheless, complications were low, and a subset of patients did receive a
      durable benefit from the procedure.

PMID- 29049005
TI  - Beliefs, attitudes, and activities of healthcare personnel about influenza and
      pneumococcal vaccines.
AB  - OBJECTIVES: Vaccination of healthcare personnel (HCP) is an effective measure for
      preventing the spread of influenza among at-risk patients. This study was
      conducted to determine influenza vaccination rates and activities among HCP
      working at a tertiary healthcare setting. METHODS: This study included 470 HCP
      (85 physicians, 134 nurses, 53 healthcare assistants, 44 paramedics, 47 medical
      secretaries, and 107 auxillary staff members) working at the emergency,
      cardiology, chest diseases, and internal medicine departments with the largest
      volume of patients with vaccination indication of two large university hospitals
      with similar medical practices and work environment. Each participant completed
      an anonymous questionnaire form. RESULTS: A total of 470 HCP participated in the
      survey. The compliance rate of the HCP to participate in the survey was 93.6%. Of
      these, 26.7% had been vaccinated against influenza. Vaccination in the survey
      year was significantly associated with having regular influenza vaccinations (OR
      48.66; 95% CI:[25.09-94.369]; P<.01); having an educational level of college or
      higher (OR 2.07; 95% CI:[1.03-4.15]; P<.05); being a physician (OR 4.25; 95%
      CI:[1.28-14.07]; P< .05); and a professional experience of more than 5 years (OR
      2.02; 95%CI:[1.13-5.62]; P< .05). Physicians recommended and prescribed the
      influenza vaccine significantly more frequently than the pneumococcal vaccine
      (37.6% vs 30.6%, P = .03, 25.9% vs 17.6%, P = .001, respectively). Among all HCP,
      the reasons for vaccination included having the opinion that the vaccine provides
      a partial protection against the infection (75.2%), reduces work force loss
      (48.8%), reduces the rates of death and severe conditions like pneumonia (43.2%),
      and reduces hospitalization (40.8%). The HCP had been vaccinated to protect
      family members (81.6%), people around (51.2%), herself/himself (47.2%), and
      patients (28%) fom infection. The reasons of not getting vaccinated against
      influenza among HCP included fear of vaccine's adverse effects (31.0%), doubts
      about its efficacy (28.9%) and safety (22.3%), and lack of adequate knowledge
      about vaccination (16.2%). CONCLUSION: Our results indicated that influenza
      vaccination rates are low in our whole HCP sample, with physicians having a
      slightly better rate than other HCP. Getting regularly vaccinated, having an
      educational level of college or higher, being a physician, and having a
      professional experience of more than 5 years positively affects the rate of
      future vaccinations. Physicians significantly more commonly recommended and
      prescribed the influenza vaccine than the pneumococcal vaccine. The most
      important reasons for getting vaccinated included having the opinion that the
      vaccine provided partial protection and intending to protect family members from
      infection. In our whole HCP sample, the reasons of not getting vaccinated against
      influenza included fear of vaccine's adverse effects and doubts about its
      efficacy and safety. Training meetings should be held for HCPs to underscore the
      importance of the influenza vaccine for protection of patients against the
      influenza.

PMID- 29049006
TI  - The dynamics of immunoglobulin V-gene usage and clonotype expansion in mice after
      prime and boost immunizations as analyzed by NGS.
AB  - In the current study, an improved NGS approach was developed to study the B-cell
      repertoire evolution in a simple mouse immunization model including only two DNA
      immunizations. The combination of 5'RACE and Ion Torrent long reads enabled
      unbiased immunoglobulin repertoire analysis even from small amounts of peripheral
      mouse blood. The B-cell population expanded by the vaccine displayed a relatively
      strong clonality. Upon priming with the first vaccine dose, we observed a
      consistent pattern of V-segment gene and CDR3 usage (public specificities).
      Interestingly, this pattern diversified with the second dose of immunization -it
      was relatively different in individual mice in spite of having received the same
      vaccine regimen (private specificities). Nevertheless, there were several
      instances in which the same public V-segment genes and CDR3s that were expanded
      after the first dose were further amplified after the second immunization. Taken
      together, it appears that the major clonotypes expanded by vaccination were
      originally a homogeneous subset that later diversified after a second dose
      leading to diverse "private" clonal compositions in different mice. These results
      established a new platform valuable to perform longitudinal analyses of the Ig
      germline gene usage and clonotype evolution throughout an immunization regimen in
      a commonly used animal model.

PMID- 29049007
TI  - Low prevalence of vaccine-type HPV infections in young women following the
      implementation of a school-based and catch-up vaccination in Quebec, Canada.
AB  - BACKGROUND: In Quebec, Canada, a school-based HPV vaccination for girls has been
      offered since 2008. The vaccine used in the program targets HPV16/18, responsible
      for ~70% of cervical cancers and HPV6/11, responsible for the majority of
      anogenital warts. The objective of this study was to assess the prevalence of HPV
      in vaccinated and unvaccinated women. METHODS: Women aged 17-29 years were
      eligible to participate. Participants' age, vaccination status and diverse risk
      factors were assessed by a computer-assisted questionnaire. Biological specimens
      were obtained by self-sampling. HPV genotyping was performed by Linear Array.
      RESULTS: A total of 2,118 women were recruited. 2,042 completed the questionnaire
      and 1,937 provided a vaginal sample. Vaccination coverage varied from 83.5% in
      women aged 17-19 to 19.1% in those aged 23-29. The overall prevalence of HPV in
      sexually active women was 39.4% (95%CI: 37.0-41.7) and 56.7% of infected women
      had multiple type infections. The prevalence of vaccine HPV types varied by age
      and vaccination status except for women aged 23-29 for whom similar results were
      observed. Vaccine HPV types were detected in 0.3%, 1.4% and 10.5% of vaccinated
      women aged 17-19, 20-23, and 23-29 (p<0.05), respectively. HPV16 or HPV18 were
      detected in 10 women having received at least one dose of vaccine. Nine of these
      women were already sexually active at the time of vaccination. CONCLUSION:
      Infections with HPV types included in the vaccine are rare in women aged less
      than 23 years and are virtually absent in those who received at least one dose of
      vaccine before sexual debut.

PMID- 29049008
TI  - Exogenous murine antimicrobial peptide CRAMP significantly exacerbates Ovalbumin
      induced airway inflammation but ameliorates oxazolone-induced intestinal colitis
      in BALB/c mice.
AB  - Cathelicidin has been reported to be multifunctional. The current study aimed to
      investigate the influences of exogenous cathelicidin-related antimicrobial
      peptide (CRAMP) on inflammatory responses in different disease models. In OVA
      induced allergic airway inflammation, CRAMP significantly enhanced the
      infiltration of inflammatory cells and accumulation of proinflammatory Th2
      cytokine IL-13 and IL-33 in bronchial alveolar lavage fluid (BALF), exacerbated
      lung tissue inflammation and airway goblet cell hyperplasia, and elevated OVA
      specific IgE level in serum. In oxazolone-induced intestinal colitis, the
      expression levels of CRAMP and its receptor FPR2 significantly increased in
      comparison with those of TNBS-induced mice, vesicle and normal controls.
      Exogenous CRAMP significantly prevented the development of ulcerative colitis,
      evidenced by improved body weight regain, decreased colons weight/length ratio,
      elevated epithelial integrity, and ameliorated colon tissue inflammation. In
      addition, pro-inflammatory cytokines TNF-alpha, IL-1beta, IL-4 and IL-13, as well
      as chemokines CXCL2 and CXCL5 for neutrophils recruitment were significantly
      decreased in CRAMP-treated mice, and epithelial repair-related factors MUC2 and
      Claudin1 were increased, determined by real time-PCR and ELISAs. The results
      indicated that although CRAMP has pro-inflammatory effects in airway, local
      application of exogenous CRAMP might be a potential approach for the treatment of
      ulcerative colitis.

PMID- 29049009
TI  - Seroepidemiology of coxsackievirus B5 in infants and children in Jiangsu
      province, China.
AB  - Coxsackievirus B5 (CV-B5) is associated with various human diseases such as viral
      encephalitis, aseptic meningitis, paralysis, herpangina, and hand, foot and mouth
      disease (HFMD). However, there is currently no effective vaccine against CV
      B5.The seroepidemiologic characteristics of CV-B5 remained unknown. A cohort
      study was carried out in 176 participants aged 6-35 months from January 2012 to
      January 2014. The serum samples were collected and tested for CV-B5 neutralizing
      antibodies (NtAbs) four times during these two years. The confirmed enterovirus
      cases were recorded through the surveillance system, and their throat or rectal
      swabs were collected for pathogen detection. According to the changes of CV-B5
      NtAbs, two CV-B5 epidemics were detected among these participants during the two
      year follow-up. Sixty-seven cases out of all participants had seroconversion in
      CV-B5 NtAbs. During the first epidemic from March 2012 to September 2012, CV-B5
      seropositivity rate increased significantly (6.8%, 12/176 vs. 21.6%, 38/176, P =
      0.000). The seroconversion rate and geometric mean fold-increase (GMFI) were
      18.2% (32/176) and 55.7, respectively; During the second epidemic from September
      2012 to January 2014, CV-B5 seropositivity rate also increased (21.6%, 38/176 vs.
      38.6%, 68/176, P = 0.000), and the seroconversion rate and GMFI were 19.9%
      (35/176) and 46.5, respectively. Only one case had CV-B5 associated HFMD during
      the two-year follow-up, and CV-B5 from the throat swab isolate was GI.D3 subtype,
      which belonged to the major pandemic strain in mainland China. CV-B5 infection
      was common in infants and children in Jiangsu province, China. Therefore, it's
      necessary to strengthen the surveillance on CV-B5 and to understand the epidemic
      characteristics of CV-B5 infection.

PMID- 29049010
TI  - Biofilm-Related Diseases and Omics: Global Transcriptional Profiling of
      Enterococcus faecium Reveals Different Gene Expression Patterns in the Biofilm
      and Planktonic Cells.
AB  - Enterococcus faecium is an opportunistic pathogen with a remarkable ability to
      acquire resistance toward multiple antibiotics, including those of last-resort
      drugs such as vancomycin and daptomycin. The occurrence of vancomycin-resistant
      E. faecium is on the rise and there is a need to understand the virulence of this
      organism. One of the factors that contributes to the virulence is the ability to
      form biofilms. Since bacteria in biofilm state are more resistant to antibiotics
      and host immune response, understanding the molecular mechanism of biofilm
      development is important to control biofilm-related diseases. The aim of this
      study was to determine the global gene expression profiles of an E. faecium
      strain, VREr5, during the early event of sessile growth compared with its
      planktonic phase through RNA-sequencing approach. The results clearly illustrated
      distinct expression profiles of the planktonic and biofilm cells. A total of 177
      genes were overexpressed in the biofilm cells. Most of them encode for proteins
      involved in adherence, such as the ebpABCfm locus. Genes associated with plasmid
      replication, gene exchange, and protein synthesis were also upregulated during
      the early event of biofilm development. Furthermore, the transcriptome analysis
      also identified genes such as fsrB, luxS, and spx that might suppress biofilm
      formation in VREr5. The putative biofilm-related bee locus was found to be
      downregulated. These new findings could provide caveats for future studies on the
      regulation and maintenance of biofilm and development of biomarkers for biofilm
      related diseases.

PMID- 29049011
TI  - "Omics" of Food-Borne Gastroenteritis: Global Proteomic and Mutagenic Analysis of
      Salmonella enterica Serovar Enteritidis.
AB  - Salmonella Enteritidis causes food-borne gastroenteritis by the two type three
      secretion systems (TTSS). TTSS-1 mediates invasion through intestinal lining, and
      TTSS-2 facilitates phagocytic survival. The pathogens' ability to infect
      effectively under TTSS-1-deficient background in host's phagocytes is poorly
      understood. Therefore, pathobiological understanding of TTSS-1-defective
      nontyphoidal Salmonellosis is highly important. We performed a comparative global
      proteomic analysis of the isogenic TTSS-1 mutant of Salmonella Enteritidis
      (M1511) and its wild-type isolate P125109. Our results showed 43 proteins were
      differentially expressed. Functional annotation further revealed that
      differentially expressed proteins belong to pathogenesis, tRNA and ncRNA
      metabolic processes. Three proteins, tryptophan subunit alpha chain, citrate
      lyase subunit alpha, and hypothetical protein 3202, were selected for in vitro
      analysis based on their functional annotations. Deletion mutants generated for
      the above proteins in the M1511 strain showed reduced intracellular survival
      inside macrophages in vitro. In sum, this study provides mass spectrometry-based
      evidence for seven hypothetical proteins, which will be subject of future
      investigations. Our study identifies proteins influencing virulence of Salmonella
      in the host. The study complements and further strengthens previously published
      research on proteins involved in enteropathogenesis of Salmonella and extends
      their role in noninvasive Salmonellosis.

PMID- 29049013
TI  - Identification and Validation of Fibroblast Growth Factor 12 Gene as a Novel
      Potential Biomarker in Esophageal Cancer Using Cancer Genomic Datasets.
AB  - Esophageal squamous cell carcinoma (ESCC) has a complex, multifactorial etiology
      in which environmental, geographical, and genetic factors play major roles. It is
      the second most common cancer among men and the fourth most common among women in
      India, with a particularly high prevalence in Northeast India. In this study, an
      integrative in silico [DAVID, NCG5.0, Oncomine, Cancer Cell Line Encyclopedia,
      and The Cancer Genome Atlas (TCGA)] approach was used to identify the potential
      biomarkers by using the available three genomic datasets on ESCC from Northeast
      India followed by its in vitro functional validation. Fibroblast Growth Factor 12
      (FGF12) gene was overexpressed in ESCC. The upregulation of FGF12 was also
      observed on ESCC of TCGA OncoPrint portal, whereas very low expression of FGF12
      gene was mapped in normal esophageal tissue on the GTEx database. Silencing of
      FGF12 showed significant inhibition in activity of tumor cell proliferation,
      colony formation, and cell migration. The upregulation of FGF12 showed
      significantly reduced survival in ESCC patients. The protein interaction analysis
      of FGF12 found the binding with MAPK8IP2 and MAPK13. High expression of FGF12
      along with MAPK8IP2, and MAPK13 proteins correlate with poor survival in ESCC
      patients. Tissue microarray also showed expression of these proteins in patients
      with ESCC. These results indicate that FGF12 has a potential role in ESCC and
      suggest that cancer genomic datasets with application of in silico approaches are
      instrumental for biomarker discovery research broadly and specifically, for the
      identification of FGF12 as a putative biomarker in ESCC.

PMID- 29049012
TI  - Transcriptome Profiling Uncovers Potential Common Mechanisms in Fetal Trisomies
      18 and 21.
AB  - Human trisomies have recently been investigated using transcriptomics approaches
      to identify the gene expression (GE) signatures characteristic of each of these
      specific aneuploidy conditions. We hypothesized that the viability of cells with
      gross genomic imbalances might be associated with the activation of resilience
      mechanisms that are common to different trisomies and that are reflected by
      specific shared GE patterns. We report in this article our microarray GE analyses
      of amniocytes from fetuses with viable trisomy conditions, trisomy 21 or trisomy
      18, to detect such common expression signatures. Comparative analysis of
      significantly differentially expressed genes in trisomies 18 and 21 revealed six
      dysregulated genes common to both: OTUD5, ADAMTSL1, TADA2A, PPID, PIAS2, and
      MAPRE2. These genes are involved in ubiquitination, protein folding, cell
      proliferation, and apoptosis. Pathway-based enrichment analyses demonstrated that
      both trisomies showed dysregulation of the PI3K/AKT pathway, cell cycle G2/M DNA
      damage checkpoint regulation, and cell death and survival, as well as inhibition
      of the upstream regulator TP53. Our data collectively suggest that trisomies 18
      and 21 share common functional GE signatures, implying that common mechanisms of
      resilience might be activated in aneuploid cells to resist large genomic
      imbalances. To the best of our knowledge, this is the first study to use global
      GE profiling data to identify potential common mechanisms in fetal trisomies.
      Studies of other trisomies using transcriptomics and multiomics approaches might
      further clarify mechanisms activated in trisomy syndromes.

PMID- 29049014
TI  - Transcriptomic-Guided Drug Repositioning Supported by a New Bioinformatics Search
      Tool: geneXpharma.
AB  - Drug repositioning is an innovative approach to identify new therapeutic
      indications for existing drugs. Drug repositioning offers the promise of reducing
      drug development timeframes and costs, and because it involves drugs that are
      already in the clinic, it might remedy some of the drug safety challenges
      traditionally associated with drug candidates that are not yet available in the
      clinic. The gene-by-drug interactions are an important dimension of optimal drug
      repositioning and development strategies. While gene-by-drug interactions have
      been curated and presented in various databases, novel bioinformatics tools and
      approaches are timely, and required with a specific focus to support drug
      positioning. We report, in this study, the design of a public web-accessible
      transcriptomic-/gene expression-guided pharmaceuticals search tool, geneXpharma (
      www.genexpharma.org ). GeneXpharma is a public platform with user-centric
      interface that provides statistically evaluated gene expressions and their drug
      interactions for 48 diseases under seven different disease categories.
      GeneXpharma is designed and organized to generate hypotheses on druggable genome
      within the disease-gene-drug triad and thus, help repositioning of drugs against
      diseases. The search system accommodates various entry points using drugs, genes,
      or diseases, which then enable researchers to extract drug repurposing candidates
      and readily export for further evaluation. Future developments aim to improve the
      geneXpharma algorithm, enrich its content, and enhance the website interface
      through addition of network visualizations and graphical display items.
      Bioinformatics search tools can help enable the convergence of drug repositioning
      and gene-by-drug interactions so as to further optimize drug development efforts
      in the future.

PMID- 29049015
TI  - JPEN Journal Club 30. The Cochrane Systematic Review-Data Collection and
      Assessment.

PMID- 29049016
TI  - Skeletal Muscle Ultrasonography in Nutrition and Functional Outcome Assessment of
      Critically Ill Children: Experience and Insights From Pediatric Disease and Adult
      Critical Care Studies [Formula: see text].
AB  - Evidence suggests that critically ill children develop muscle wasting, which
      could affect outcomes. Muscle ultrasound has been used to track muscle wasting
      and association with outcomes in critically ill adults but not children. This
      review aims to summarize methodological considerations of muscle ultrasound,
      structural findings, and possibilities for its application in the assessment of
      nutrition and functional outcomes in critically ill children. Medline, Embase,
      and CINAHL databases were searched up until April 2016. Articles describing
      skeletal muscle ultrasound in children and critically ill adults were analyzed
      qualitatively for details on techniques and findings. Thickness and cross
      sectional area of various upper and lower body muscles have been studied to
      quantify muscle mass and detect muscle changes. The quadriceps femoris muscle is
      one of the most commonly measured muscles due to its relation to mobility and is
      sensitive to changes over time. However, the margin of error for quadriceps
      thickness is too wide to reliably detect muscle changes in critically ill
      children. Muscle size and its correlation with strength and function also have
      not yet been studied in critically ill children. Echogenicity, used to detect
      compromised muscle structure in neuromuscular disease, may be another property
      worth studying in critically ill children. Muscle ultrasound may be useful in
      detecting muscle wasting in critically ill children but has not been shown to be
      sufficiently reliable in this population. Further study of the reliability and
      correlation with functional outcomes and nutrition intake is required before
      muscle ultrasound is routinely employed in critically ill children.

PMID- 29049017
TI  - Legionnaires' Disease Outbreaks and Cooling Towers, New York City, New York, USA.
AB  - The incidence of Legionnaires' disease in the United States has been increasing
      since 2000. Outbreaks and clusters are associated with decorative, recreational,
      domestic, and industrial water systems, with the largest outbreaks being caused
      by cooling towers. Since 2006, 6 community-associated Legionnaires' disease
      outbreaks have occurred in New York City, resulting in 213 cases and 18 deaths.
      Three outbreaks occurred in 2015, including the largest on record (138 cases).
      Three outbreaks were linked to cooling towers by molecular comparison of human
      and environmental Legionella isolates, and the sources for the other 3 outbreaks
      were undetermined. The evolution of investigation methods and lessons learned
      from these outbreaks prompted enactment of a new comprehensive law governing the
      operation and maintenance of New York City cooling towers. Ongoing surveillance
      and program evaluation will determine if enforcement of the new cooling tower law
      reduces Legionnaires' disease incidence in New York City.

PMID- 29049018
TI  - Prevalence of Single and Multiple Leading Causes of Death by Race/Ethnicity Among
      US Adults Aged 60 to 79 Years.
AB  - INTRODUCTION: Diabetes, cancer, cardiovascular disease (CVD) (coronary artery
      disease, heart attack, and angina pectoris), and chronic lung disease (emphysema,
      chronic bronchitis, and chronic obstructive pulmonary disease) are major causes
      of death in the United States. The objective of this study was to assess
      racial/ethnic differences in the prevalence of these conditions as cause of death
      among people aged 60 to 79 years with one or more of these conditions. METHODS:
      We used data on the prevalence of major chronic conditions from the National
      Health Interview Survey on 56,290 adults aged 60 to 79 years who reported having
      any of the chronic conditions assessed in the National Health Interview Survey
      for 2006 through 2014. We compared trends with age for 11 single and multiple
      conditions. Analyses employed multinomial logistic regression models. RESULTS:
      Hispanics and non-Hispanic blacks had the greatest prevalence of diabetes, and
      non-Hispanic whites had the greatest prevalence of cancer and chronic lung
      disease. The prevalence of multiple chronic diseases in an individual varied less
      by race/ethnicity. An exception was the prevalence of having both diabetes and
      CVD, which was higher among Hispanics and non-Hispanic blacks than non-Hispanic
      whites. Non-Hispanic blacks aged 65 years and 75 years had higher odds of having
      diabetes and cancer than non-Hispanic whites at the same ages. Hispanics had
      lower odds of having CVD with cancer or chronic lung disease than non-Hispanic
      whites. Women had a lower age-specific prevalence than men for most of the 11
      single and multiple conditions. Most chronic diseases showed an inverse
      relationship with education and a higher prevalence in the South than in other
      regions. CONCLUSION: Strong racial/ethnic differences exist in the prevalence of
      single chronic conditions, but differences are lower for prevalence of multiple
      conditions. Comparing races/ethnicities, the same disease dyads and triads may
      occur more often in different orders.

PMID- 29049019
TI  - Mammography Use in Portugal: National Health Survey 2014.
AB  - INTRODUCTION: Understanding the patterns of mammography use and monitoring
      changes in use are essential to improving national health policy for breast
      cancer control. We aimed to describe the use of mammography in Portugal and to
      identify the determinants of its nonuse and underuse by examining data from the
      National Health Survey 2014. METHODS: We analyzed data on 8,758 women aged 30
      years or older. We defined women at an eligible age for mammography as women aged
      45 to 69. Women who reported a previous mammography test were classified as ever
      users and grouped according to time since the most recent test. We computed the
      prevalence of mammography use, and we used Poisson regression models to obtain
      age-adjusted and education-adjusted prevalence ratios and 95% confidence
      intervals. RESULTS: The overall prevalence of mammography use was 80.0%, whereas
      nonuse was 20.0% and underuse 27.3% among users. The prevalence of nonuse and
      underuse were lower and associations with sociodemographic characteristics, use
      of health care services, and behavioral factors were stronger among women aged 45
      to 69 than among women aged 30 to 44 and women aged 70 or older. The prevalence
      of mammography use was generally higher in the northern areas of Portugal than in
      southern areas and varied by marital status, educational level, and household
      size. A more frequent use of health care services and healthier behaviors were
      associated with lower prevalences of both nonuse and underuse. CONCLUSION: This
      study illustrates inequalities in mammography use and provides useful information
      for better allocation of resources in breast cancer screening.

PMID- 29049020
TI  - Comparison of Methods for Estimating Prevalence of Chronic Diseases and Health
      Behaviors for Small Geographic Areas: Boston Validation Study, 2013.
AB  - INTRODUCTION: Local health authorities need small-area estimates for prevalence
      of chronic diseases and health behaviors for multiple purposes. We generated city
      level and census-tract-level prevalence estimates of 27 measures for the 500
      largest US cities. METHODS: To validate the methodology, we constructed
      multilevel logistic regressions to predict 10 selected health indicators among
      adults aged 18 years or older by using 2013 Behavioral Risk Factor Surveillance
      System (BRFSS) data; we applied their predicted probabilities to census
      population data to generate city-level, neighborhood-level, and zip-code-level
      estimates for the city of Boston, Massachusetts. RESULTS: By comparing the
      predicted estimates with their corresponding direct estimates from a locally
      administered survey (Boston BRFSS 2010 and 2013), we found that our model-based
      estimates for most of the selected health indicators at the city level were close
      to the direct estimates from the local survey. We also found strong correlation
      between the model-based estimates and direct survey estimates at neighborhood and
      zip code levels for most indicators. CONCLUSION: Findings suggest that our model
      based estimates are reliable and valid at the city level for certain health
      outcomes. Local health authorities can use the neighborhood-level estimates if
      high quality local health survey data are not otherwise available.

PMID- 29049021
TI  - Do Black Women's Religious Beliefs About Body Image Influence Their Confidence in
      Their Ability to Lose Weight?
AB  - INTRODUCTION: Black women are disproportionately burdened by obesity but maintain
      body satisfaction and strong religious commitment. Although faith-based weight
      loss interventions have been effective at promoting weight loss among blacks,
      little is known about how body image and religious views contribute to weight
      related beliefs among religious black women. The purpose of this study was to
      examine whether demographic and health history factors, religious involvement,
      and beliefs about body image could explain motivation and confidence to lose
      weight among a church-affiliated sample of black women. METHODS: We recruited 240
      church-affiliated black women aged 18 to 80 years (average age, 55 y; SD, 12.3)
      in 2014 from 6 black churches that participated in a larger study, Project FIT
      (Faith Influencing Transformation), a clustered, diabetes/heart disease/stroke
      intervention among black women and men. We used baseline data from Project FIT to
      conduct a cross-sectional study consisting of a survey. Variables approaching
      significance in preliminary correlation and chi2 analyses were included in 2
      multiple linear regression models examining motivation and confidence in ability
      to lose weight. RESULTS: In final regression models, body mass index was
      associated with motivation to lose weight (beta = 0.283, P < .001), and beliefs
      about body image in relation to God predicted confidence to lose weight (beta =
      0.180, P = .01). CONCLUSION: Faith-based, weight-loss interventions targeting
      black women should emphasize physical well-being and highlight the health
      benefits of weight management rather than the benefits of altering physical
      appearance and should promote positive beliefs about body image, particularly
      relating to God.

PMID- 29049022
TI  - Cardiovascular adaptation to hypoxia and the role of peripheral resistance.
AB  - Systemic vascular pressure in vertebrates is regulated by a range of factors: one
      key element of control is peripheral resistance in tissue capillary beds. Many
      aspects of the relationship between central control of vascular flow and
      peripheral resistance are unclear. An important example of this is the
      relationship between hypoxic response in individual tissues, and the effect that
      response has on systemic cardiovascular adaptation to oxygen deprivation. We show
      here how hypoxic response via the HIF transcription factors in one large vascular
      bed, that underlying the skin, influences cardiovascular response to hypoxia in
      mice. We show that the response of the skin to hypoxia feeds back on a wide range
      of cardiovascular parameters, including heart rate, arterial pressures, and body
      temperature. These data represent the first demonstration of a dynamic role for
      oxygen sensing in a peripheral tissue directly modifying cardiovascular response
      to the challenge of hypoxia.

PMID- 29049024
TI  - Phase transitions and thermal entanglement of the distorted Ising-Heisenberg spin
      chain: topology of multiple-spin exchange interactions in spin ladders.
AB  - We consider a symmetric spin-1/2 Ising-XXZ double sawtooth spin ladder obtained
      from distorting a spin chain, with the XXZ interaction between the interstitial
      Heisenberg dimers (which are connected to the spins based on the legs via an
      Ising-type interaction), the Ising coupling between nearest-neighbor spins of the
      legs and rungs spins, respectively, and additional cyclic four-spin exchange
      (ring exchange) in the square plaquette of each block. The presented analysis
      supplemented by results of the exact solution of the model with infinite periodic
      boundary implies a rich ground state phase diagram. As well as the quantum phase
      transitions, the characteristics of some of the thermodynamic parameters such as
      heat capacity, magnetization and magnetic susceptibility are investigated. We
      prove here that among the considered thermodynamic and thermal parameters, solely
      heat capacity is sensitive versus the changes of the cyclic four-spin exchange
      interaction. By using the heat capacity function, we obtain a singularity
      relation between the cyclic four-spin exchange interaction and the exchange
      coupling between pair spins on each rung of the spin ladder. All thermal and
      thermodynamic quantities under consideration should be investigated by regarding
      those points which satisfy the singularity relation. The thermal entanglement
      within the Heisenberg spin dimers is investigated by using the concurrence, which
      is calculated from a relevant reduced density operator in the thermodynamic
      limit.

PMID- 29049025
TI  - Diverse carrier mobility of monolayer BNC x : a combined density functional
      theory and Boltzmann transport theory study.
AB  - BNC x monolayer as a kind of two-dimensional material has numerous chemical
      atomic ratios and arrangements with different electronic structures. Via
      calculations on the basis of density functional theory and Boltzmann transport
      theory under deformation potential approximation, the band structures and carrier
      mobilities of BNC x (x  =  1,2,3,4) nanosheets are systematically investigated.
      The calculated results show that BNC2-1 is a material with very small band gap
      (0.02 eV) among all the structures while other BNC x monolayers are
      semiconductors with band gap ranging from 0.51 eV to 1.32 eV. The carrier
      mobility of BNC x varies considerably from tens to millions of cm2 V-1 s-1. For
      BNC2-1, the hole mobility and electron mobility along both x and y directions can
      reach 105 orders of magnitude, which is similar to the carrier mobility of
      graphene. Besides, all studied BNC x monolayers obviously have anisotropic hole
      mobility and electron mobility. In particular, for semiconductor BNC4, its hole
      mobility along the y direction and electron mobility along the x direction
      unexpectedly reach 106 orders of magnitude, even higher than that of graphene.
      Our findings suggest that BNC x layered materials with the proper ratio and
      arrangement of carbon atoms will possess desirable charge transport properties,
      exhibiting potential applications in nanoelectronic devices.

PMID- 29049023
TI  - The future of graduate and postdoctoral training in the biosciences.
AB  - This article summarizes the outcomes of the second national conference on the
      Future of Bioscience Graduate and Postdoctoral Training. Five topics were
      addressed during the conference: diversity in leadership positions; mentoring;
      modernizing the curriculum; experiential learning; and the need for better data
      on trainees. The goal of the conference was to develop a consensus around these
      five topics and to recommend policies that can be implemented by academic and
      research institutions and federal funding agencies in the United States.

PMID- 29049026
TI  - Dipole-switch induced modification of the emissive response of carbon nanotubes.
AB  - The interaction of carbon nanotubes with the molecular dipole switch spiropyran
      is expected to affect the optical response of the tubes. Until now, the need of
      anchor groups to immobilize the switches on the tubes has hindered the
      experimental observation of the effects of switching on the emission behavior of
      the tubes. Here we present spiropyran-carbon nanotube complexes obtained by
      micelle swelling. This method does not require any anchor nor sophisticated
      chemistry to warrant close tube-switch proximity. For the first time, we observe
      the shifts predicted theoretically and their effect on the tubes' excitation and
      emission energies.

PMID- 29049028
TI  - Electronic and magnetic properties of multiferroic ScFeO3 available from
      diffraction experiments.
AB  - Electronic and magnetic properties of ferric ions (3d 5) in multiferroic ScFeO3
      are puzzling, in part because they are different from the only other multiferroic
      known to possess the same polar chemical structure, BiFeO3. Open questions about
      ScFeO3 can be addressed by confronting observations with results for G-type
      antiferromagnetism allowed by the lithium niobate (LiNbO3)-like parent R3c
      structure. Calculated structure factors for resonant x-ray diffraction include
      all charge-like quadrupoles allowed by symmetry, and if experimental results for
      ScFeO3 subsequently imply they are different from zero then ferric ions cannot be
      in the high-spin 6S state. The same type of experiment can reveal the moment
      direction in the G-type antiferromagnetism, according to our calculations, and
      thereby contribute to understanding magnetic anisotropy. Furthermore, structure
      factors for magnetic neutron diffraction by ScFeO3 include Dirac multipoles that
      are time-odd and parity-odd, e.g. dipoles that are often called anapoles or
      toroidal moments. Apart from Dirac multipoles, the conventional approach to the
      interpretation of neutron Bragg diffraction data will be inadequate if ferric
      ions (Fe3+) are not in the high-spin 6S state, because the scattering amplitude
      includes more than simple dipole moments in the general case.

PMID- 29049027
TI  - Atlas ranking and selection for automatic segmentation of the esophagus from CT
      scans.
AB  - In radiation treatment planning, the esophagus is an important organ-at-risk that
      should be spared in patients with head and neck cancer or thoracic cancer who
      undergo intensity-modulated radiation therapy. However, automatic segmentation of
      the esophagus from CT scans is extremely challenging because of the structure's
      inconsistent intensity, low contrast against the surrounding tissues, complex and
      variable shape and location, and random air bubbles. The goal of this study is to
      develop an online atlas selection approach to choose a subset of optimal atlases
      for multi-atlas segmentation to the delineate esophagus automatically. We
      performed atlas selection in two phases. In the first phase, we used the
      correlation coefficient of the image content in a cubic region between each atlas
      and the new image to evaluate their similarity and to rank the atlases in an
      atlas pool. A subset of atlases based on this ranking was selected, and
      deformable image registration was performed to generate deformed contours and
      deformed images in the new image space. In the second phase of atlas selection,
      we used Kullback-Leibler divergence to measure the similarity of local-intensity
      histograms between the new image and each of the deformed images, and the
      measurements were used to rank the previously selected atlases. Deformed contours
      were overlapped sequentially, from the most to the least similar, and the overlap
      ratio was examined. We further identified a subset of optimal atlases by
      analyzing the variation of the overlap ratio versus the number of atlases. The
      deformed contours from these optimal atlases were fused together using a modified
      simultaneous truth and performance level estimation algorithm to produce the
      final segmentation. The approach was validated with promising results using both
      internal data sets (21 head and neck cancer patients and 15 thoracic cancer
      patients) and external data sets (30 thoracic patients).

PMID- 29049029
TI  - Diffusion of interstitials in metallic systems, illustration of a complex study
      case: aluminum.
AB  - While diffusion mechanisms of interstitial elements in fcc systems are generally
      well-known, especially in the case of H atoms, we show in this work that even in
      the case of a simple metallic system (aluminum), the diffusion of interstitials
      exhibits a wide variety of paths and mechanisms that depend on the specie. We
      used an approach based on first-principles calculations associated with kinetic
      Monte-Carlo simulations and a multi-state diffusion formalism to compute the
      diffusion coefficients of five interstitial elements: hydrogen, boron, carbon,
      nitrogen and oxygen. For instance, at the atomic scale, whilst we find that C
      atoms prefer to be located in octahedral sites (labeled o) rather than in
      tetrahedral positions (labeled t), we find one additional stable position in the
      lattice (M). The diffusion through these three stable positions are thus studied
      in detail. In the case of B atoms, for which the tetrahedral site is found
      unstable, the diffusion path is between o-o sites. Similarly, in the case of
      oxygen, t positions are found to be the only stable positions (o are unstable)
      and the path of migration, along t-t direction, is found through a twice
      degenerated asymmetric transition state. In the case of H and N atoms for which t
      and o sites are stable, we explain why the only path is along the t-o direction.
      Finally, we discuss explicit formulas to compute coefficients of diffusion of
      interstitials in fcc structures.

PMID- 29049030
TI  - Evidence for the confinement of magnetic monopoles in quantum spin ice.
AB  - Magnetic monopoles are hypothesised elementary particles connected by Dirac
      strings that behave like infinitely thin solenoids (Dirac 1931 Proc. R. Soc. A
      133 60). Despite decades of searching, free magnetic monopoles and their Dirac
      strings have eluded experimental detection, although there is substantial
      evidence for deconfined magnetic monopole quasiparticles in spin ice materials
      (Castelnovo et al 2008 Nature 326 411). Here we report the detection of a
      hierarchy of unequally-spaced magnetic excitations via high resolution inelastic
      neutron spectroscopic measurements on the quantum spin ice candidate [Formula:
      see text] [Formula: see text] [Formula: see text]. These excitations are well
      described by a simple model of monopole pairs bound by a linear potential (Coldea
      et al Science 327 177) with an effective tension of 0.642(8) K [Formula: see
      text] at 1.65 K. The success of the linear potential model suggests that these
      low energy magnetic excitations are direct spectroscopic evidence for the
      confinement of magnetic monopole quasiparticles in the quantum spin ice candidate
      [Formula: see text] [Formula: see text] [Formula: see text].

PMID- 29049031
TI  - Effect of hydrostatic pressure on the superconducting properties of quasi-1D
      superconductor K2Cr3As3.
AB  - K2Cr3As3 is a newly discovered quasi-1D superconductor with a T c  =  6.1 K and
      an upper critical field u 0 H c2(0)  ~  40 T three times larger than the Pauli
      paramagnetic limit u 0 H p that is suggestive of a spin-triplet Cooper pairing.
      In this paper, we have investigated the effects of hydrostatic pressure on its T
      c and u 0 H c2 by measuring the ac magnetic susceptibility chi'(T) under magnetic
      fields at various hydrostatic pressures up to 7.5 GPa. The major findings
      include: (1) T c is suppressed gradually to below 2 K at 7.5 GPa; (2) the
      estimated u 0 H c2(0) decreases dramatically to below u 0 H p above ~2 GPa and
      becomes slight lower than the orbital limiting field [Formula: see text]
      estimated from the initial slope of upper critical field via [Formula: see text] 
      =  -0.73T cdH c2/[Formula: see text] in the clean limit; (3) the estimated Maki
      parameter alpha  =  ?2[Formula: see text]/H p drops from 4 at ambient pressure to
      well below 1 at P  >  2 GPa, suggesting the crossover from Pauli paramagnetic
      limiting to orbital limiting in the pair breaking process upon increasing
      pressure. These observations suggested that the application of hydrostatic
      pressure could drive K2Cr3As3 away from the ferromagnetic instability and lead to
      a breakdown of the spin-triplet pairing channel. We have also made a side-by-side
      comparison and discussed the distinct effects of chemical and physical pressures
      on the superconducting properties of K2Cr3As3.

PMID- 29049032
TI  - Large-scale calculations of thermoelectric transport coefficients: a case study
      of gamma-graphyne with point defects.
AB  - Defects such as vacancies and impurities could have profound effects on the
      transport properties of thermoelectric materials. However, it is usually quite
      difficult to directly calculate the thermoelectric properties of defect
      containing systems via first-principles methods since a very large supercell is
      required. In this work, based on the linear response theory and the kernel
      polynomial method, we present an efficient approach that can help to calculate
      the thermoelectric transport coefficients of a large system containing millions
      of atoms at arbitrary chemical potential and temperature. As a prototype example,
      we consider dilute vacancies and hydrogen impurities in a large-scale gamma
      graphyne sheet and discuss their effects on the thermoelectric transport
      properties.

PMID- 29049033
TI  - Squeezed Dirac and topological magnons in a bosonic honeycomb optical lattice.
AB  - Quantum information storage using charge-neutral quasiparticles is expected to
      play a crucial role in the future of quantum computers. In this regard, magnons
      or collective spin-wave excitations in solid-state materials are promising
      candidates in the future of quantum computing. Here, we study the quantum
      squeezing of Dirac and topological magnons in a bosonic honeycomb optical lattice
      with spin-orbit interaction by utilizing the mapping to quantum spin-[Formula:
      see text] XYZ Heisenberg model on the honeycomb lattice with discrete Z2 symmetry
      and a Dzyaloshinskii-Moriya interaction. We show that the squeezed magnons can be
      controlled by the Z2 anisotropy and demonstrate how the noise in the system is
      periodically modified in the ferromagnetic and antiferromagnetic phases of the
      model. Our results also apply to solid-state honeycomb (anti)ferromagnetic
      insulators.

PMID- 29049035
TI  - Optical properties of graphene nanocones under electric and magnetic fields.
AB  - Here we present a theoretical study of the optical properties of graphene
      nanocones tuned by external electric and magnetic fields. We investigate the
      effects of the size and topology of the carbon nanostructures on the density of
      states and on the electro- and magneto-absorption of linearly polarized
      electromagnetic radiation in different nanocone geometries. We find that the
      electric field induces changes in the electric charge distribution mainly at the
      cone edges. In the infrared range the absorption coefficient shows a peculiar
      dependence on the electric field (magnitude and direction) and on the photon
      polarization for all investigated structures. Our results suggest that the
      electric field may be used to control the electric charge at the apex and for a
      selective light absorption. The presence of an axial magnetic field induces new
      features in the nanocone density of states due to the induced localization
      effects. For high fields the density of states exhibits a sequence of peaks
      resembling the graphene Landau spectra. The magneto-absorption spectra present a
      series of resonances strongly sensitive to the photon polarization opening routes
      for manipulation of the optical responses.

PMID- 29049034
TI  - Complex-based OCT angiography algorithm recovers microvascular information better
      than amplitude- or phase-based algorithms in phase-stable systems.
AB  - Optical coherence tomography angiography (OCTA) is increasingly becoming a
      popular inspection tool for biomedical imaging applications. By exploring the
      amplitude, phase and complex information available in OCT signals, numerous
      algorithms have been proposed that contrast functional vessel networks within
      microcirculatory tissue beds. However, it is not clear which algorithm delivers
      optimal imaging performance. Here, we investigate systematically how amplitude
      and phase information have an impact on the OCTA imaging performance, to
      establish the relationship of amplitude and phase stability with OCT signal-to
      noise ratio (SNR), time interval and particle dynamics. With either repeated A
      scan or repeated B-scan imaging protocols, the amplitude noise increases with the
      increase of OCT SNR; however, the phase noise does the opposite, i.e. it
      increases with the decrease of OCT SNR. Coupled with experimental measurements,
      we utilize a simple Monte Carlo (MC) model to simulate the performance of
      amplitude-, phase- and complex-based algorithms for OCTA imaging, the results of
      which suggest that complex-based algorithms deliver the best performance when the
      phase noise is  <  ~40 mrad. We also conduct a series of in vivo vascular imaging
      in animal models and human retina to verify the findings from the MC model
      through assessing the OCTA performance metrics of vessel connectivity, image SNR
      and contrast-to-noise ratio. We show that for all the metrics assessed, the
      complex-based algorithm delivers better performance than either the amplitude- or
      phase-based algorithms for both the repeated A-scan and the B-scan imaging
      protocols, which agrees well with the conclusion drawn from the MC simulations.

PMID- 29049036
TI  - Histone deacetylase inhibitor BG45-mediated HO-1 expression induces apoptosis of
      multiple myeloma cells by the JAK2/STAT3 pathway.
AB  - Multiple myeloma (MM) is a hematological malignancy that is characterized by the
      clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs)
      represent a new type of molecular targeted therapy for different types of cancers
      and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein
      levels of CD138 mononuclear cells from MM patients were higher than those in
      healthy donors. Therefore, we investigated the effects of a novel class I HDAC
      inhibitor BG45 on MM cells in vitro. BG45 downmodulated heme oxygenase 1 (HO-1)
      when class I HDACs decreased in MM cells. HO-1 is a target for the treatment of
      MM. Moreover, BG45 induced hyperacetylation of histone H3 and inhibited the
      growth, especially the apoptosis of MM cell lines. Treatment with BG45 induced
      apoptosis by downregulating bcl-2 and Bcl-xl, upregulating Bax and other
      antiapoptotic proteins and activating poly(ADP-ribose)polymerase, and decreasing
      protein levels of p-JAK2 and p-STAT3. These effects were partly blocked by HO-1.
      Correspondingly, BG45 led to an accumulation in the G0/G1 phase, accompanied by
      decreased levels of CDK4 and phospho-retinoblastoma protein, an increased level
      of p21, and a moderately reduced level of CDK2. Clinical use of single agents was
      limited because of toxic side effects and drug resistance. However, combining
      BG45 with lenalidomide exerted synergistic effects. In conclusion, we verified
      the potent antimyeloma activity of this novel HDAC inhibitor and that the
      combination of BG45 and lenalidomide is a new method for MM treatment. Thus, BG45
      may be applicable to the treatment of MM and other hematological malignancies.

PMID- 29049037
TI  - Fractures and the gut microbiome.
AB  - PURPOSE OF REVIEW: The role of the gut microbiome in the pathogenesis of several
      inflammatory, non-AIDS comorbidities, such as cardiovascular disease, cognitive
      impairment and liver disease has become a focus of recent research. Low bone
      mineral density (BMD) and increased fracture incidence in people living with HIV
      (PLWH) is also widely reported, however, the relationship between alterations in
      the gut microbiome and bone disease in PLWH has not been previously reviewed.
      RECENT FINDINGS: Murine models that manipulate the gut microbiome, either through
      breeding of 'germ-free' mice or antibiotic-depleted gut microbiome, show
      differences in bone mineral density and bone mass in those with altered gut
      microbiome. This effect is reported to be driven via changes in the gut-immune
      skeletal axis, with changes favouring bone resorption. Several inflammatory
      conditions wherever bone loss is a prominent feature, such as rheumatoid
      arthritis and inflammatory bowel disease, have also reported alterations in the
      gut microbiome, which are associated with bone loss, again through changes in the
      gut-immune-skeletal axis. SUMMARY: The interplay between the gut microbiome and
      the immune-skeletal axis in HIV represents a complex relationship. Alterations in
      the gut microbiome, which induce an activated immune phenotype and inflammatory
      milieu are associated with non-AIDS comorbidities in PLWH and bone loss in
      several other conditions characterized by chronic immune activation and
      inflammation. It is, therefore, likely that there are comparable effects between
      altered gut microbiome and bone loss in HIV, however, further research is
      required to better define this relationship in populations of PLWH.

PMID- 29049038
TI  - Binaural integration: a challenge to overcome for children with hearing loss.
AB  - PURPOSE OF REVIEW: Access to bilateral hearing can be provided to children with
      hearing loss by fitting appropriate hearing devices to each affected ear. It is
      not clear, however, that bilateral input is properly integrated through hearing
      devices to promote binaural hearing. In the present review, we examine evidence
      indicating that abnormal binaural hearing continues to be a challenge for
      children with hearing loss despite early access to bilateral input. RECENT
      FINDINGS: Behavioral responses and electrophysiological data in children,
      combined with data from developing animal models, reveal that deafness in early
      life disrupts binaural hearing and that present hearing devices are unable to
      reverse these changes and/or promote expected development. Possible limitations
      of hearing devices include mismatches in binaural place, level, and timing of
      stimulation. Such mismatches could be common in children with hearing loss. One
      potential solution is to modify present device fitting beyond providing
      audibility to each ear by implementing binaural fitting targets. SUMMARY: Efforts
      to better integrate bilateral input could improve spatial hearing in children
      with hearing loss.

PMID- 29049039
TI  - Serum Cyclosporine Levels: The Influence of the Time Interval Between
      Interrupting the Infusion and Obtaining the Samples: A Randomized Clinical Trial.
AB  - BACKGROUND: There are controversies regarding the best way to collect blood
      samples for cyclosporine A (CsA) serum levels when this immunosuppressant is
      administered continuously through a silicone central venous catheter (CVC) to
      hematopoietic stem cell transplant recipients. OBJECTIVE: The aim of this study
      was to verify the effect of the time elapsed between the interruption of a
      continuous intravenous CsA infusion and the collection of blood samples on CsA
      serum levels. METHODS: This randomized 2-group clinical trial involved 32 adults.
      In group A, blood samples were collected immediately after interrupting the
      medication from peripheral vein and CVC lines. In group B, the same procedures
      were performed 5 minutes after interrupting the infusion. RESULTS: We did not
      observe influence of the time elapsed between interruption of the infusion and
      collection of the samples, independent of the collection mode and the volume
      discarded (P > .05). The line used for the infusion maintained a constant high
      level when compared with different moments of collection (P > .05), whereas in
      the other lines, there was a significant increase when compared with the levels
      obtained at 24 hours and 7 days after CsA start (P = .00). CONCLUSION: The CVC
      line free from cyclosporine can safely be used to collect blood. The procedure
      can be performed immediately after interrupting the infusion, and discarding 5 mL
      is sufficient to obtain accurate levels. IMPLICATIONS FOR PRACTICE: The results
      can help nurses choose how to collect blood samples through the CVC, thus
      preventing patients from having a painful and stressful procedure such as
      peripheral venipuncture.

PMID- 29049040
TI  - The Relationship Between Nutritional Risks and Cancer-Related Fatigue in Patients
      With Colorectal Cancer Fast-Track Surgery.
AB  - BACKGROUND: Measurement of cancer-related fatigue and nutrition in the same
      colorectal cancer patient group using fast-track surgery has never been examined
      previously. The association between fatigue and nutritional status in the same
      patient group is thus worthwhile to be investigated. OBJECTIVE: The aim of this
      study was to evaluate the relationship between fatigue and nutrition risk factors
      in colorectal cancer patients with fast-track surgery. METHODS: This is a single
      arm, observational study. Seventy eligible postoperative patients with colorectal
      cancer fast-track surgery were enrolled in this study. Patients completed the
      Cancer Fatigue Scale and the Patient-Generated Subjective Global Assessment (PG
      SGA) besides routine perioperative laboratory examination. RESULTS: In this
      study, all patients were found to have cancer-related fatigue; 20% of the
      patients had severe fatigue. Furthermore, 94.29% of the patients were
      malnourished according to the PG-SGA score; the average was 15.585.18. Fatigue
      severity was significantly, positively correlated with nutrition status. White
      blood cells and serum calcium were significantly, positively related to both
      Cancer Fatigue Scale and PG-SGA scores. CONCLUSION: Fatigue and malnutrition
      commonly exist in patients with colorectal cancer experiencing fast-track
      surgery. Fatigue may reflect the nutritional status in this group of patients.
      IMPLICATIONS FOR PRACTICE: Clinical nursing staff need to evaluate patients'
      fatigue status and nutritional status to provide the suitable clinical
      intervention when needed.

PMID- 29049041
TI  - The impact of lifestyle intervention on atrial fibrillation.
AB  - PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac
      arrhythmia, attributable to several factors that may be amenable through
      lifestyle modification. There is emerging evidence to suggest that the successful
      management of several cardiovascular risk factors [obesity, hypertension (HTN),
      diabetes mellitus, and obstructive sleep apnea (OSA)] can lead to fewer
      complications and atrial fibrillation prevention. However, the long-term
      sustainability and reproducibility of these effects have yet to be explored in
      larger studies. This review explores recent findings for exercise and lifestyle
      modifications to promote alternative strategies to interventional therapy for
      atrial fibrillation management. RECENT FINDINGS: Several studies have highlighted
      the impact of established modifiable risk factors on atrial fibrillation burden
      and the potential for effective risk management in a clinical setting. Higher
      SBP, HTN, pulse pressure, and antihypertensive treatment have been linked to
      alterations in left atrial diameter and dysfunction. Effective treatment of HTN
      has been shown to reduce all-cause mortality, cardiovascular mortality, and the
      overall risk of developing atrial fibrillation. Given the impact of obesity on
      the development of atrial fibrillation, diet has been identified as a modifiable
      risk factor for stroke. Maintenance of proper glycemic control through structured
      exercise training for prediabetes and continuous positive airway pressure
      utilization for OSA, have also been correlated with reductions in atrial
      fibrillation recurrence. SUMMARY: Early intervention of modifiable
      cardiometabolic factors leads to lifestyle and behavioral change, which has
      significant potential to evolve atrial fibrillation management in the coming
      years.

PMID- 29049042
TI  - Atrial fibrillation occurring transiently with stress.
AB  - PURPOSE OF REVIEW: Atrial fibrillation may be detected in the setting of an acute
      stressor, such as medical illness or surgery. It is uncertain if atrial
      fibrillation detected in these settings (AFOTS: atrial fibrillation occurring
      transiently with stress) is secondary to a reversible trigger or is simply
      paroxysmal atrial fibrillation. This distinction is critical for clinicians, who
      must decide if AFOTS can be dismissed as a reversible phenomenon, or if it
      signals the need for chronic therapy; in particular, anticoagulation. RECENT
      FINDINGS: Published studies report incidences of AFOTS ranging from 1 to 44% in
      patients with acute medical illness and 1 to 35% following noncardiac surgery.
      The highest estimates have been reported in critically ill patients and in those
      undergoing continuous monitoring. A small number of studies have reported the
      recurrence of atrial fibrillation after AFOTS to be 55-68% within 5 years of
      medical illness and 37% within 1 year after noncardiac surgery. These studies are
      limited by retrospective design and low-sensitivity ascertainment. SUMMARY: AFOTS
      commonly occurs in patients with acute medical illness or in the postoperative
      state, and atrial fibrillation recurs in over 50% of individuals. Prospective
      postdischarge studies using sensitive atrial fibrillation detection strategies
      are needed to define the relationship between AFOTS and clinical atrial
      fibrillation.

PMID- 29049043
TI  - Challenges of healthcare administration: optimizing quality and value at an
      affordable cost in pediatric cardiology.
AB  - PURPOSE OF REVIEW: The purpose of this review is to explore the paradigm shift in
      healthcare delivery that will need to take place over the next few years away
      from an emphasis on supply-driven health care to better quality transparent
      driven health care whose focus is on the consumer's best interest. RECENT
      FINDINGS: The current healthcare system is fragmented and costs continue to rise.
      The best way to contain costs is to improve quality to the consumer, the patient.
      Physicians and hospitals need to align in a team-based approach that allows
      physicians to understand current costs and how to strive toward a focus on
      healthcare outcomes. Pediatric cardiology is a unique discipline that cares for
      patients with complex congenital conditions that will span their lifetime and
      also involves not just cardiology but surgery, intensive care, anesthesia,
      nursing, and a host of inpatient and ambulatory services. Understanding what
      matters to the patient and his/her family and presenting quality outcomes in a
      transparent fashion will gradually allow a shift to take place away from
      physician visits, tests ordered, and procedures performed. This can only be
      achieved with physicians, given the appropriate tools to understand costs, value,
      and outcomes and models where the hospitals and physicians are aligned. SUMMARY:
      The transformation to a value-based healthcare system is beginning and pediatric
      cardiologists need to be educated, given the appropriate resources, receive
      appropriate feedback, and patients need to be part of the solution so that care
      providers can understand what matters most to them.

PMID- 29049044
TI  - The relevance of healthy diets for the prevention of frailty and cognitive
      impairment.

PMID- 29049045
TI  - Nutrition, physical activity, and lifestyle factors in prostate cancer
      prevention.
AB  - PURPOSE OF REVIEW: To review current evidence for prostate cancer prevention with
      nutrition, physical activity, and lifestyle interventions and identify future
      research directions. RECENT FINDINGS: Multiple preclinical and observational
      studies have observed that diet, exercise, and lifestyle interventions may play a
      role in mitigating disease progression, mortality, and overall disease burden for
      high-grade and fatal prostate cancer. Increased vegetable and fruit intakes,
      decreased red meat and saturated fat intakes, and increased exercise are
      potentially associated with decreased risk of incident disease and increased
      progression-free, prostate cancer-specific, and overall survival. Randomized
      controlled trials (RCTs) have demonstrated that selenium and vitamin C
      supplements are ineffective in preventing incident prostate cancer and that
      vitamin E supplements potentially increase incident prostate cancer risk. A large
      RCT of a high vegetable diet intervention among prostate cancer patients on
      active surveillance, the Men's Eating and Living study, will soon complete
      analysis. An RCT for an exercise intervention among men with metastatic castrate
      resistant prostate cancer is currently accruing. SUMMARY: Although preclinical
      and observational studies have identified potential benefits for high vegetable,
      low fat, low meat diets, and increased exercise, Level I evidence is limited. To
      inform clinical care, future research should focus on RCTs evaluating clinical
      effectiveness.

PMID- 29049046
TI  - Determination of death in donation after circulatory death: an ethical propriety.
AB  - PURPOSE OF REVIEW: The recently developed donation after circulatory death (DCD)
      heart transplant technique, pioneered by Papworth Hospital in the UK, involves
      the use of extracorporeal perfusion technologies to restart the donor heart in
      situ and thereby restore the donor's own circulation, after first isolating the
      donor's cerebral circulation. By restoring the circulation in the deceased donor,
      even if the cerebral circulation is excluded, the Papworth technique challenges
      the acceptability of death determination in DCD. RECENT FINDINGS: This study uses
      as its exemplar case the Papworth DCD heart technique to review and make wider
      comment about death determination in DCD. We seek to answer three challenges to
      ethical propriety raised by the Papworth technique: death determination using the
      permanence standard (common to all DCD practice); restoration of heart
      contractility and circulation in the body; and active prevention of the
      restoration of brain circulation by use of a cross-clamp to isolate the cerebral
      circulation. SUMMARY: The Papworth technique for heart DCD does not compromise
      the permanence standard for declaring death and therefore respects the dead donor
      rule in the UK, but perhaps elsewhere the law would need to change to refer to
      the cessation of circulation in the brain.

PMID- 29049047
TI  - Analysis of Radionuclide Deposition Ratios from the Fukushima-Daiichi Incident.
AB  - This paper will examine deposition patterns of four radionuclides following the
      Fukushima-Daiichi accident. For nearly 13 d following the event, fission products
      were released into the environment through planned venting procedures and
      hydrogen explosions. To assist the government of Japan (GOJ) in the assessment of
      the releases, the National Nuclear Security Administration's Consequence
      Management Response Team (CMRT) deployed and took nearly 3 mo of measurements
      using airborne radiation sensors, fixed monitors, high purity germanium (HPGe)
      detectors, and health physics survey equipment. From the HPGe detector in-situ
      results gathered by the CMRT and GOJ teams, the depositions of Cs, Cs, Cs, and I
      were examined as a function of latitude and longitude. Deposition ratios were
      calculated to express how each radionuclide was deposited relative to Cs. In
      addition, the first 30 d of results were compared to the isotopic ratios listed
      in the Federal Radiological Monitoring and Assessment Center (FRMAC) Dose
      Assessment Manual Volume 2 Nuclear Power Plant default scenario. This was
      completed to analyze how the default FRMAC values compared with actual
      measurements. For Cs:Cs and Cs:Cs (1 wk after shutdown), the ratios were 0.969 +/
      0.025 and 0.13 +/- 0.007, respectively. These were significantly different from
      the FRMAC default values of 1.6 and 0.4, but they were of the same order of
      magnitude. Spatially, larger ratios with high uncertainties were recorded near
      Tokyo, over 200 km from the accident site. The I to Cs ratios, as expected,
      decayed exponentially over time but were significantly higher than FRMAC values.
      Six ratios were greater than 20 within 10 d after shutdown compared to the FRMAC
      default value of 9.9. In addition, the highest ratios were located less than 75
      km to the southwest of the plant. Comparing all the isotopic ratios to the FRMAC
      manual illustrated differences between the default values and the actual field
      results. This is at least partly due to the fact that the FRMAC default values
      are based on an average between a pressurized water reactor and boiling water
      reactor release. These results of the comparison illustrate that the Assessment
      Manual default values should only be used when no other data are available.

PMID- 29049048
TI  - Urinary Excretion of Yttrium-90 after Radioembolization with Yttrium-90-Labeled
      Resin-based Microspheres.
AB  - In radioembolic therapy (RET) of hepatic malignancies using yttrium-90 (Y)
      labeled resin microspheres, radiation protection is primarily concerned with
      avoiding contamination by radioactive spheres. However, as Y is bound to the
      microsphere surface by a potentially reversible ion-exchange process, the aim of
      this study was to assess the extent of the potential excreted activity in urine.
      After RET with Y-labeled resin-based microspheres, urinary excretion of free Y
      was prospectively analyzed in 51 interventions (n = 45 patients) by sampling
      urine over 48 h (two 24-h intervals) consecutively. The measured urinary
      concentration of Y, normalized to the administered microsphere activity, was a
      median of 58.5 kBq L GBq (range = 3.5-590.9 kBq L GBq) and 17.8 kBq L GBq (1.8
      58.8 kBq L GBq) for the first and second 24-h periods after administration,
      respectively (p <= 0.0001, F = 28.4, result from ANOVA). The total excreted
      activity significantly decreased (p <= 0.0001) from a median of 72.5 kBq in the
      first 24-h period to a median of 22.1 kBq in the second 24-h period. Urinary
      excretion of free Y after resin-based RET occurs for a longer period and at a
      higher activity excretion than previously published, which has to be considered
      when patients are either hospitalized or return home after RET. Existing
      approaches for patient hospitalization, especially in temporary radiation
      protection areas, justified by the previously reported lower excretion rate,
      should be re-evaluated, and as a consequence, the current product safety
      information and handling recommendations for Y-labeled resin-based microspheres
      may need to be revised.

PMID- 29049049
TI  - Treatable traits of chronic airways disease.
AB  - PURPOSE OF REVIEW: To describe the rationale on which the treatable traits
      approach to the management of airways disease is based and the issues that need
      to be considered for its implementation in clinical practice. RECENT FINDINGS: In
      clinical practice, treatable traits can be classified according to both endotypes
      and phenotypes, broadly grouped within pulmonary, extrapulmonary, environmental
      and behavioural factors. Specific investigations and treatments are undertaken
      for each of the traits rather than a 'one size fits all' stepwise approach to
      pharmacological treatment which currently represents the core of asthma and
      chronic obstructive pulmonary disease (COPD) guidelines. Although there is strong
      evidence of the benefit of the treatable traits approach to specific traits in
      asthma and/or COPD, there is uncertainty regarding the preferred method of
      implementation, efficacy and cost-effectiveness of multidimensional intervention
      programmes in clinical practice. It is likely that 'master protocols' for
      randomized controlled trials will be required to evaluate such multiple
      interventions in broad populations of patients with airways disease. SUMMARY:
      Current evidence suggests that the precision medicine approach based on the
      identification and treatment of treatable traits is preferable to a 'one-size
      fits-all' stepwise approach to the treatment of airways disease, although high
      quality evidence to guide the practical application of this multidimensional
      management strategy is now required. VIDEO ABSTRACT.

PMID- 29049050
TI  - An update on noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features.
AB  - PURPOSE OF REVIEW: Noninvasive encapsulated follicular variant of papillary
      thyroid carcinoma (PTC) has been established in the literature as a clinically
      indolent tumor. Despite this, it was traditionally treated like all other PTCs.
      In an attempt to reduce overtreatment of this entity, a panel of experts
      reclassified this entity as noninvasive follicular neoplasm with papillary-like
      nuclear features (NIFTP). This reclassification has led to a flurry of literature
      elucidating the molecular, cytologic and clinical parameters of this 'new' entity
      and the implications for patient management. The purpose of this review is to
      examine the latest literature on this tumor and explore how its emergence has
      impacted our current understanding of the diagnosis, management and outcomes in
      this entity. RECENT FINDINGS: NIFTP is a low grade tumor with an indolent
      clinical course. Recent studies have begun to document the variable incidence of
      NIFTP, the ultrasound and cytologic findings, and the impact of the NIFTP
      terminology on established rates of malignancy in fine-needle aspiration and
      clinical outcome studies. SUMMARY: The recent literature on molecular,
      radiographic and cytologic characteristics of NIFTP are building our
      understanding of this neoplasm and support its indolent nature.

PMID- 29049051
TI  - Baseline Understanding of Urinary Incontinence and Prolapse in New Urogynecology
      Patients.
AB  - OBJECTIVES: Investigators sought to assess whether age was related to patient
      understanding of pelvic floor disorders; given studies show that increased age is
      associated with lower health literacy. METHODS: This was a cross-sectional survey
      of new urogynecology patients. Enrolled participants completed a survey including
      demographics, history of urinary incontinence (UI) and pelvic organ prolapse
      symptoms and treatment, the Prolapse and Incontinence Knowledge Questionnaire
      (PIKQ), self-assessment of UI and prolapse knowledge, and a pelvic anatomy
      diagram to label. To achieve 80% power to detect a 2-point difference in PIKQ
      score, 33 subjects were required per age group (<65 and >=65 years old). RESULTS:
      One hundred thirty-five of 160 new urogynecologic patients completed the survey
      (84% response rate). Thirty-seven participants were older than 65 years, and 98
      were younger than 65 years. Total PIKQ scores (maximum, 24), the primary outcome,
      for the older and younger groups were 15.3 and 15.0, respectively (P = 0.7). The
      2 groups self-rated UI and prolapse knowledge similarly, rating knowledge as
      excellent, very good, or good in 60% (P = 0.3) and 40% (P = 0.2) of subjects,
      respectively. CONCLUSIONS: Baseline patient understanding of UI and pelvic organ
      prolapse was low as assessed by PIKQ score and was not influenced by age.

PMID- 29049052
TI  - A Cost-Utility Analysis of Nonsurgical Treatments for Stress Urinary Incontinence
      in Women.
AB  - OBJECTIVE: The objective of this study was to perform a cost-utility analysis of
      nonsurgical treatments for stress urinary incontinence (SUI) in healthy adult
      women with a health system perspective over a 1-year time horizon. METHODS: A
      decision tree model was constructed to evaluate the following nonsurgical
      treatment options for SUI in a simulated healthy adult female cohort who had
      failed Kegel exercises: pelvic floor muscle therapy (PFMT), a disposable tampon
      device (Impressa), a self-fitting intravaginal incontinence device (Uresta), and
      a traditional incontinence pessary. Published data and consultation with health
      care providers were used to estimate efficacies and costs. Health utility
      estimates were derived from existing literature. Deterministic sensitivity
      analyses were performed as well as Monte Carlo probabilistic sensitivity analysis
      to account for the impact of parameter uncertainty on costs and efficacies for
      each treatment. Our primary outcome was the highest net monetary benefit (NMB),
      which represents the monetary value of the health benefits less the treatment
      costs. The standard willingness-to-pay threshold of US $50,000 per quality
      adjusted life year was used. RESULTS: The utility of SUI in an otherwise healthy
      patient was 0.81 +/- 0.16 and for subjective cure was 0.93 +/- 0.08. Using base
      case estimates, PFMT was the most cost-effective treatment with an NMB of US
      $44,098. The Impressa tampon, Uresta, and traditional pessary had NMBs of US
      $43,970, $43,785, and $42,846, respectively. The probabilistic sensitivity
      analysis confirmed PFMT to be the most cost-effective treatment option at a
      willingness to pay of US $50,000 per quality-adjusted life year. CONCLUSIONS: The
      findings of our cost-utility analysis favor PFMT as the most cost-effective
      nonsurgical treatment option for SUI. Cost-effectiveness for 1 year of treatment
      was also favorable for Impressa and Uresta. In jurisdictions where there is no
      public funding for PFMT, Impressa or Uresta are alternatives for women wishing to
      avoid surgery.

PMID- 29049053
TI  - Treatment options for posttraumatic epilepsy.
AB  - PURPOSE OF REVIEW: Posttraumatic seizures (PTS) and posttraumatic epilepsy (PTE)
      are common and debilitating consequences of traumatic brain injury (TBI). Early
      PTS result in secondary brain injury by raising intracranial pressure and
      worsening cerebral edema and metabolic crisis. PTE is a localization-related
      epilepsy strongly associated with TBI severity, but risk factors for PTE and
      epileptogenesis are incompletely understood and are active areas of research.
      Medical management of PTS in adults and children is reviewed. Surgical options
      for posttraumatic drug-resistant epilepsy are also discussed. RECENT FINDINGS:
      Continuous electroencephalography is indicated for children and adults with TBI
      and coma because of the high incidence of nonconvulsive seizures, periodic
      discharges, and associated secondary brain injury in this population.
      Neuroinflammation is a central component of secondary brain injury and appears to
      play a key role in epileptogenesis. Levetiracetam is increasingly used for
      seizure prophylaxis in adults and children, but variability remains. SUMMARY: PTS
      occur commonly after TBI and are associated with secondary brain injury and worse
      outcomes in adults and children. Current medical and surgical management options
      for PTS and PTE are reviewed.

PMID- 29049054
TI  - Clinical Aspects of Miscarriage.
AB  - It is estimated that 750,000 to 1,000,000 miscarriages occur every year in the
      United States. Women experiencing a miscarriage enter the healthcare system in a
      variety of ways. A family may be seen for a miscarriage in the prenatal clinic,
      the emergency department, same-day surgical department, or perhaps the labor and
      birth unit. Nurses must be prepared to guide and support these families.
      Understanding the clinical aspects of miscarriage as well as the emotional care
      of families experiencing early pregnancy loss is important to nurses in all areas
      of the medical center. Clinical aspects of miscarriage are reviewed along with
      the needed emotional care for families experiencing the most common cause of
      early pregnancy loss.

PMID- 29049056
TI  - The Microbiome and Maternal Newborn Health.

PMID- 29049055
TI  - Oxidized Regenerated Cellulose/Collagen Dressings: Review of Evidence and
      Recommendations.
AB  - OBJECTIVE: Healthcare systems are being challenged to manage increasing numbers
      of nonhealing wounds. Wound dressings are one of the first lines of defense in
      wound management, and numerous options exist. The oxidized regenerated cellulose
      (ORC)/collagen dressing may offer healthcare providers a robust and cost
      effective tool for use in a variety of wounds. DESIGN: A multidisciplinary panel
      meeting was convened to discuss the use of ORC/collagen dressings in wound care
      and provide practice recommendations. A literature search was conducted to
      provide a brief review of the peer-reviewed studies published between January
      2000 and March 2016 to inform the meeting. SETTING: A 2-day panel meeting
      convened in February 2017. PARTICIPANTS: Healthcare providers with experience
      using ORC/collagen dressings. This multidisciplinary panel of 15 experts in wound
      healing included podiatrists, wound care specialists (doctors, certified wound
      care nurses, and research scientists), and an orthopedist. RESULTS: The
      literature search identified 58 articles, a majority of which were low levels of
      evidence (69.3% were level 3 or lower). Panel members identified wound types,
      such as abrasions, burns, stalled wounds, diabetic foot ulcers, and pressure
      injuries, where ORC/collagen dressing use could be beneficial. Panel members then
      provided recommendations and technical pearls for the use of ORC/collagen
      dressings in practice. Barriers to ORC/collagen dressing use were discussed, and
      potential resolutions were offered. CONCLUSIONS: An ORC/collagen dressing can be
      a critical tool for clinicians to help manage a variety of wounds. Clinical and
      economic studies comparing standard-of-care dressings and plain collagen
      dressings to ORC/collagen dressings are needed.

PMID- 29049057
TI  - The Postpartum Maternal and Newborn Microbiomes.
AB  - Biological and environmental changes to maternal and newborn microbiomes in the
      postnatal period can affect health outcomes for the mother-baby dyad. Postpartum
      sleep deprivation and unmet dietary needs can alter commensal bacteria within the
      body and disrupt gut-brain communication. Perineal injury and breast infections
      also change microbial community composition, potentiating an environment favoring
      pathogen growth. The gut microbiome refers to the collection of microorganisms
      working in harmony. Disruptions within the gut microbiome and gut-brain
      communication may lead to postpartum depression, a potentially devastating
      sequela. Postnatal newborn changes to the gut and skin microbiome materialize
      quickly after birth and are profoundly influenced by mode of birth, feeding
      method, and bathing and skin care practices. During the newborn period, infant
      microbiomes are highly vulnerable and susceptible to multiple influences.
      Maternal-newborn nurses have a valuable role in helping mothers and newborns
      promote healthy microbiomes. Factors that influence the rapidly changing
      postnatal microbiome of the mother and her newborn, and the role nurses have to
      positively influence immediate and long-term health outcomes are presented.

PMID- 29049059
TI  - Status of High Body Weight Among Nurse-Family Partnership Children.
AB  - PURPOSE: Increased prevalence of high levels of body weight in early childhood
      has become a public health concern, given its potential association with adult
      obesity and related comorbidities. Both socioeconomic status and race-ethnicity
      are related to increased prevalence. The purpose of this study was to identify
      additional risk factors common to children of low-income families; and to guide
      quality improvement initiatives within home visiting programs, potentially
      fostering more desirable physical development outcomes. STUDY DESIGN AND METHODS:
      A cohort of children (n = 14,318) of all mothers enrolled in Nurse-Family
      Partnership between 2007 and 2010 was evaluated. Measures consisted of
      demographics, health behaviors, and physical growth metrics collected by
      specially educated nurses during the course of home visits that also delivered
      the program model. Measures of weight (W) versus length (L) were converted to
      percentiles using the Centers for Disease Control and Prevention-World Health
      Organization norms with high W/L (>=97.7th percentile) defining a binary outcome.
      Multiple logistic regression modeling was then used to derive risk models for
      that outcome. RESULTS: Across each of the four time points for body measures
      (child's age 6, 12, 18, and 24 months), race-ethnicity, prepregnancy body mass
      index (BMI), maternal weight gain, and breastfeeding duration emerged as common
      risk factors. CLINICAL IMPLICATIONS: Moderation of weight gain during pregnancy,
      extending breastfeeding duration, and normalization of BMI before subsequent
      pregnancies may potentially serve as means of lowering the prevalence of high
      body weight levels in young children of low-income families served by home
      visitors.

PMID- 29049058
TI  - The Neonatal Microbiome: Implications for Neonatal Intensive Care Unit Nurses.
AB  - Nursing care of the neonate in the neonatal intensive care unit (NICU) is
      complex, due in large part to various physiological challenges. A newer and less
      well-known physiological consideration is the neonatal microbiome, the community
      of microorganisms, both helpful and harmful, that inhabit the human body. The
      neonatal microbiome is influenced by the maternal microbiome, mode of infant
      birth, and various aspects of NICU care such as feeding choice and use of
      antibiotics. The composition and diversity of the microbiome is thought to
      influence key health outcomes including development of necrotizing enterocolitis,
      late-onset sepsis, altered physical growth, and poor neurodevelopment. Nurses in
      the NICU play a key role in managing care that can positively influence the
      microbiome to promote more optimal health outcomes in this vulnerable population
      of newborns.

PMID- 29049060
TI  - The "States" of Newborn Screening.

PMID- 29049061
TI  - The Art of Parenting at Night.

PMID- 29049062
TI  - Opioid Use in Pregnancy.

PMID- 29049063
TI  - The Dangers of Youth Football.

PMID- 29049064
TI  - Affordability and Availability of Pasteurized Donor Human Milk.

PMID- 29049065
TI  - Giving Hope to Refugee Families: Carry the Future.

PMID- 29049067
TI  - Sudden Unexpected Postnatal Collapse and Sudden Unexpected Infant Death.

PMID- 29049068
TI  - The Maternal Gut Microbiome During Pregnancy.

PMID- 29049069
TI  - The Maternal Infant Microbiome: Considerations for Labor and Birth.

PMID- 29049070
TI  - Noninfectious Fever in the Near-Term Pregnant Rat Induces Fetal Brain
      Inflammation: A Model for the Consequences of Epidural-Associated Maternal Fever.
AB  - BACKGROUND: Women laboring with epidural analgesia experience fever much more
      frequently than do women who chose other forms of analgesia, and maternal
      intrapartum fever is associated with numerous adverse consequences, including
      brain injury in the fetus. We developed a model of noninfectious inflammatory
      fever in the near-term pregnant rat to simulate the pathophysiology of epidural
      associated fever and hypothesized that it would produce fetal brain inflammation.
      METHODS: Twenty-four pregnant Sprague-Dawley rats were studied at 20 days
      gestation (term: 22 days). Dams were treated by injection of rat recombinant
      interleukin (IL)-6 or vehicle at 90-minute intervals, and temperature was
      monitored every 30 minutes. Eight hours after the first treatment, dams were
      delivered of fetuses and then killed. Maternal IL-6 was measured at delivery.
      Fetal brains (n = 24) were processed and stained for ED-1/CD68, a marker for
      activated microglia, and cell counts in the lateral septal and hippocampal brain
      regions were measured. Fetal brains were also stained for cyclooxygenase-2 (COX
      2), a downstream marker of neuroinflammation. Eight fetal brains were further
      analyzed for quantitative forebrain COX-2 by Western blotting compared to a beta
      actin standard. Maternal temperature and IL-6 levels were compared between
      treatments, as were cell counts, COX-2 staining, and COX-2 levels by Mann-Whitney
      U test, repeated-measures analysis of variance, or Fisher exact test, as
      appropriate. RESULTS: Injection of rat IL-6 at 90-minute intervals produced an
      elevation of maternal temperature compared to vehicle (P < .0001). IL-6 levels
      were elevated to clinically relevant levels at delivery in IL-6 compared to
      vehicle-treated animals (mean +/- standard deviation: 923 +/- 97 vs 143 +/- 94
      pg/mL, P = .0006). ED-1-stained cells were present in significantly higher
      numbers in fetal brains from IL-6 compared to saline-treated dams (median
      [interquartile range]: caudal hippocampus, 99 [94-104] and 64 [57-68],
      respectively, P = .002; lateral septum, 102 [96-111] and 68 [65-69],
      respectively, P = .002), as well as COX-2 immunostaining (lateral septum, 22 [20
      26] and 17 [15-18], respectively, P = .005; dorsal hippocampus, 27 [22-32] and 16
      [14-19], respectively, P = .013) and quantitative COX-2 Western blotting activity
      (mean +/- standard error of the mean: vehicle, 0% of beta-actin intensity versus
      IL-6, 41.5% +/- 24%, P < .001). CONCLUSIONS: Noninfectious inflammatory fever is
      inducible in the near-term pregnant rat by injection of IL-6 at levels comparable
      to those observed during human epidural labor analgesia. Maternal IL-6 injection
      causes neuroinflammation in the fetus.

PMID- 29049072
TI  - Effect of Stellate Ganglion Block on the Regional Hemodynamics of the Upper
      Extremity: A Randomized Controlled Trial.
AB  - BACKGROUND: The success of stellate ganglion block (SGB) is traditionally
      determined on the basis of findings such as Horner's syndrome, temperature rise
      in the face, hyperemia of the tympanic membrane, and nasal congestion. However,
      decreases in vascular resistance and increases in blood flow in the arm may be
      more meaningful findings. To date, the effect of SGB on the regional hemodynamics
      of the arm has not been evaluated using pulsed-wave Doppler ultrasound. METHODS:
      A total of 52 patients who were to undergo orthopedic surgery of the forearm were
      randomly assigned to either the mepivacaine group (SGB with 5 mL of 0.5%
      mepivacaine) or the saline group (SGB with 5 mL of normal saline). Before
      surgery, a single anesthesiologist performed a SGB under ultrasound guidance. The
      temperature of the upper extremity and the resistance index and blood flow in the
      brachial artery were measured before SGB, 15 and 30 minutes after SGB, and 1 hour
      after surgery. The severity of pain, requirement for rescue analgesics, and side
      effects of the local anesthetic agent were all documented. RESULTS: After SGB,
      the resistance index decreased significantly and the blood flow increased
      significantly in the brachial artery of members of the mepivacaine group (15
      minutes: P = .004 and P < .001, respectively; 30 minutes: P < .001 and P < .001,
      respectively). However, these values normalized after surgery. The severity of
      pain, need for rescue analgesics, and incidence of adverse effects were not
      significantly different between the 2 groups. CONCLUSIONS: Although SGB did not
      decrease the pain associated with forearm surgery, ultrasound-guided SGB did
      increase blood flow and decrease vascular resistance in the arm. Therefore,
      pulsed-wave Doppler may be used to monitor the success of SGB.

PMID- 29049073
TI  - Postoperative Outcomes in Obstructive Sleep Apnea Patients Undergoing Cardiac
      Surgery: A Systematic Review and Meta-analysis of Comparative Studies.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common comorbidity in patients
      undergoing cardiac surgery and may predispose patients to postoperative
      complications. The purpose of this meta-analysis is to determine the evidence of
      postoperative complications associated with OSA patients undergoing cardiac
      surgery. METHODS: A literature search of Cochrane Database of Systematic Reviews,
      Medline, Medline In-process, Web of Science, Scopus, EMBASE, Cochrane Central
      Register of Controlled Trials, and CINAHL until October 2016 was performed. The
      search was constrained to studies in adult cardiac surgical patients with
      diagnosed or suspected OSA. All included studies must report at least 1
      postoperative complication. The primary outcome is major adverse cardiac or
      cerebrovascular events (MACCEs) up to 30 days after surgery, which includes death
      from all-cause mortality, myocardial infarction, myocardial injury, nonfatal
      cardiac arrest, revascularization process, pulmonary embolism, deep venous
      thrombosis, newly documented postoperative atrial fibrillation (POAF), stroke,
      and congestive heart failure. Secondary outcome is newly documented POAF. The
      other exploratory outcomes include the following: (1) postoperative tracheal
      intubation and mechanical ventilation; (2) infection and/or sepsis; (3) unplanned
      intensive care unit (ICU) admission; and (4) duration of stay in hospital and
      ICU. Meta-analysis and meta- regression were conducted using Cochrane Review
      Manager 5.3 (Cochrane, London, UK) and OpenBUGS v3.0, respectively. RESULTS:
      Eleven comparative studies were included (n = 1801 patients; OSA versus non-OSA:
      688 vs 1113, respectively). MACCEs were 33.3% higher odds in OSA versus non-OSA
      patients (OSA versus non-OSA: 31% vs 10.6%; odds ratio [OR], 2.4; 95% confidence
      interval [CI], 1.38-4.2; P = .002). The odds of newly documented POAF (OSA versus
      non-OSA: 31% vs 21%; OR, 1.94; 95% CI, 1.13-3.33; P = .02) was higher in OSA
      compared to non-OSA. Even though the postoperative tracheal intubation and
      mechanical ventilation (OSA versus non-OSA: 13% vs 5.4%; OR, 2.67; 95% CI, 1.03
      6.89; P = .04) were significantly higher in OSA patients, the length of ICU stay
      and hospital stay were not significantly prolonged in patients with OSA compared
      to non-OSA. The majority of OSA patients were not treated with continuous
      positive airway pressure therapy. Meta-regression and sensitivity analysis of the
      subgroups did not impact the OR of postoperative complications for OSA versus non
      OSA groups. CONCLUSIONS: Our meta-analysis demonstrates that after cardiac
      surgery, MACCEs and newly documented POAF were 33.3% and 18.1% higher odds in OSA
      versus non-OSA patients, respectively.

PMID- 29049074
TI  - Physiology and Role of Intraocular Pressure in Contemporary Anesthesia.
AB  - More than 26 million Americans suffer with cataracts, and with 3.6 million
      cataract extractions performed annually in the United States, it is the most
      common surgical procedure. The integrity of the delicate structures of the eye
      that mediate vision is dependent on the intraocular pressure (IOP). Yet, IOP acts
      to compress the vessels within the globe-akin to a Starling resistor-and is a key
      component that determines the ocular perfusion pressure, defined as the
      difference between arterial pressure and IOP. The retina is one of the most
      metabolically active tissues in the body, and its functional integrity is
      dependent on an adequate blood supply, with retinal function linearly related to
      the ocular perfusion pressure. Retinal cell death has been demonstrated at low
      perfusion pressures (below 50 mm Hg). Modern ophthalmic surgery involves globe
      irrigation, manipulation, and instrumentation, resulting in dynamic pressure
      fluxes within the eye. Marked elevations of IOP (up to 4-5 times the normal
      value) with consequent borderline retinal and optic disk perfusion pressures
      occur for prolonged periods during many ophthalmic procedures. General surgeries,
      including laparoscopic, spinal, and cardiac procedures, especially, with their
      demand for steep Trendelenburg or prolonged prone positioning and/or hypotensive
      anesthesia, can induce IOP changes and ocular perfusion imbalance. These rapid
      fluctuations in IOP, and so in perfusion, play a role in the pathogenesis of the
      visual field defects and associated ocular morbidity that frequently complicate
      otherwise uneventful surgeries. The exact etiology of such outcomes is
      multifactorial, but ocular hypoperfusion plays a significant and frequently
      avoidable role. Those with preexisting compromised ocular blood flow are
      especially vulnerable to intraoperative ischemia, including those with
      hypertension, diabetes, atherosclerosis, or glaucoma. However, overly aggressive
      management of arterial pressure and IOP may not be possible given a patient's
      comorbidity status, and it potentially exposes the patient to risk of
      catastrophic choroidal hemorrhage. Anesthetic management significantly influences
      the pressure changes in the eye throughout the perioperative period. Strategies
      to safeguard retinal perfusion, reduce the ischemic risk, and minimize the
      potential for expulsive bleeding must be central to the anesthetic techniques
      selected. This review outlines: important physiological principles; ophthalmic
      and general procedures most likely to develop damaging IOP levels and their
      causative factors; the effect of anesthetic agents and techniques on IOP; recent
      scientific evidence highlighting the significance of perfusion changes during
      surgery; and key aspects of postoperative visual loss and management approaches
      for high-risk patients presenting for surgery.

PMID- 29049075
TI  - Anesthesia Information Management Systems.
AB  - Anesthesia information management systems (AIMS) have evolved from simple,
      automated intraoperative record keepers in a select few institutions to widely
      adopted, sophisticated hardware and software solutions that are integrated into a
      hospital's electronic health record system and used to manage and document a
      patient's entire perioperative experience. AIMS implementations have resulted in
      numerous billing, research, and clinical benefits, yet there remain challenges
      and areas of potential improvement to AIMS utilization. This article provides an
      overview of the history of AIMS, the components and features of AIMS, and the
      benefits and challenges associated with implementing and using AIMS. As AIMS
      continue to proliferate and data are increasingly shared across multi
      institutional collaborations, visual analytics and advanced analytics techniques
      such as machine learning may be applied to AIMS data to reap even more benefits.

PMID- 29049076
TI  - Fatigue Risk Management: The Impact of Anesthesiology Residents' Work Schedules
      on Job Performance and a Review of Potential Countermeasures.
AB  - Long duty periods and overnight call shifts impair physicians' performance on
      measures of vigilance, psychomotor functioning, alertness, and mood.
      Anesthesiology residents typically work between 64 and 70 hours per week and are
      often required to work 24 hours or overnight shifts, sometimes taking call every
      third night. Mitigating the effects of sleep loss, circadian misalignment, and
      sleep inertia requires an understanding of the relationship among work schedules,
      fatigue, and job performance. This article reviews the current Accreditation
      Council for Graduate Medical Education guidelines for resident duty hours,
      examines how anesthesiologists' work schedules can affect job performance, and
      discusses the ramifications of overnight and prolonged duty hours on patient
      safety and resident well-being. We then propose countermeasures that have been
      implemented to mitigate the effects of fatigue and describe how training programs
      or practice groups who must work overnight can adapt these strategies for use in
      a hospital setting. Countermeasures include the use of scheduling interventions,
      strategic naps, microbreaks, caffeine use during overnight and extended shifts,
      and the use of bright lights in the clinical setting when possible or personal
      blue light devices when the room lights must be turned off. Although this review
      focuses primarily on anesthesiology residents in training, many of the mitigation
      strategies described here can be used effectively by physicians in practice.

PMID- 29049077
TI  - Persistence and Adherence to Psychostimulants, and Psychological Well-Being Up to
      3 Years After Specialized Treatment of Adult Attention-Deficit/Hyperactivity
      Disorder: A Naturalistic Follow-Up Study.
AB  - BACKGROUND: Little is known about the long-term persistence and adherence of
      psychostimulant use in adults with attention-deficit/hyperactivity disorder
      (ADHD) and its relationship to their psychological well-being. METHODS: The
      persistence and adherence to psychostimulants and psychological well-being were
      examined in adults with ADHD in a naturalistic follow-up, starting directly after
      discharge from their specialized treatment of ADHD at an outpatient ADHD clinic.
      Ninety-six patients were included at the time of discharge, who were interviewed
      by telephone at 6 months, 1 year, and 3 years after discharge. RESULTS: At the
      time of discharge, 78% used a psychostimulant prescribed by a psychiatrist. Of
      those on psychostimulants at the time of discharge, approximately half still used
      any of these psychostimulants 3 years after discharge. However, adherence rates
      were good for those who persisted to use psychostimulants. The female sex and
      middle educational level (relative to a higher educational level) were near
      significantly related to nonpersistence, and having a higher educational level
      and the combined ADHD subtype were related to nonadherence. In turn, nonadherence
      was related to worse general functioning, lower mood, and poorer sleep quality.
      CONCLUSIONS: The importance of adherence should be discussed at the time of
      discharge, especially with female ADHD patients, those with a higher educational
      level, and those with a combined ADHD subtype, because nonadherence is associated
      with poorer outcomes.

PMID- 29049078
TI  - Hearts and Minds: Real-Life Cardiotoxicity With Clozapine in Psychosis.
AB  - BACKGROUND: Schizophrenia has a 1% prevalence in the population; 30% of these
      patients are treatment refractory. Clozapine is the only drug licensed to treat
      treatment refractory psychosis, but concerns about potential adverse effects
      result in only a proportion of eligible patients being treated. Although a well
      documented neutropenia risk is mitigated by routine blood testing, cardiac
      toxicity is a commonly cited reason to discontinue clozapine treatment. However,
      there is little data on the real-life cardiac outcomes in those receiving
      clozapine treatment. METHODS: Retrospective review of electrocardiogram,
      echocardiogram, and clinical outcomes in 39 inpatients with treatment-refractory
      schizophrenia, treated with clozapine and other antipsychotic medication,
      referred for cardiology opinion. RESULTS: Commonest reasons for referral were
      development of left ventricular (LV) impairment or sinus tachycardia with normal
      LV function. Patients were reviewed by a range of cardiologists, receiving varied
      interventions.Median LV ejection fraction in the clozapine group was normal
      (52%). Serial echocardiograms demonstrated that clozapine-treated patients with
      LV impairment had no change in LV ejection fraction over a 4-month follow-up.
      Left ventricular ejection fraction did not differ between patients treated with
      clozapine and other antipsychotics. However, over an 11-year follow-up period,
      48% of patients had discontinued clozapine treatment. CONCLUSIONS: This
      naturalistic study demonstrates that clozapine is not associated with significant
      cardiac mortality or morbidity. There is a real need for multidisciplinary
      working between specialist cardiologists and psychiatrists caring for these
      complex patients to facilitate optimal long-term physical and mental health
      outcomes.

PMID- 29049079
TI  - Some Thoughts About Racial Disparities.

PMID- 29049080
TI  - Extra-glissonian Approach for Total Laparoscopic Left Hepatectomy: A Prospective
      Cohort Study.
AB  - Laparoscopic liver resection under hemihepatic vascular inflow control has
      advantages over Pringle's maneuver, especially in patients with cirrhosis. From
      January 2016 to August 2016, 7 patients who underwent total laparoscopic left
      hepatectomy under hemihepatic vascular inflow occlusion using the extra
      glissonian approach were included in this study. All were hepatitis B carriers
      and 4 had cirrhosis. The mean operation time was 247 minutes. The mean
      transection time was 110 minutes. No patient needed additional Pringle's
      maneuver. The mean intraoperative blood loss was 74 ml and no patient required
      blood transfusion. No open conversion happened. Postoperatively, no patient
      developed complications and there was no perioperative mortality. The mean
      resection margin was 2 cm. The mean hospital stay was 6 days. Upon a mean follow
      up of 9 months, no patient developed tumor recurrence. The technique of total
      laparoscopic left hepatectomy using extra-glissonian approach was safe and
      feasible. The early surgical outcomes were good.

PMID- 29049081
TI  - Mentor Tutoring: An Efficient Method for Teaching Laparoscopic Colorectal
      Surgical Skills in a General Hospital.
AB  - OBJECTIVE: We retrospectively assessed the efficacy of our mentor tutoring system
      for teaching laparoscopic colorectal surgical skills in a general hospital.
      MATERIALS AND METHODS: A series of 55 laparoscopic colectomies performed by 1
      trainee were evaluated. Next, the learning curves for high anterior resection
      performed by the trainee (n=20) were compared with those of a self-trained
      surgeon (n=19). RESULTS: Cumulative sum analysis and multivariate regression
      analyses showed that 38 completed cases were needed to reduce the operative time.
      In high anterior resection, the mean operative times were significantly shorter
      after the seventh average for the tutored surgeon compared with that for the self
      trained surgeon. In cumulative sum charting, the curve reached a plateau by the
      seventh case for the tutored surgeon, but continued to increase for the self
      trained surgeon. CONCLUSIONS: Mentor tutoring effectively teaches laparoscopic
      colorectal surgical skills in a general hospital setting.

PMID- 29049082
TI  - Inhibiting social support from massage-like stroking increases morphine
      dependence.
AB  - Our previous studies showed that altering solely the drug experience of the cage
      mates with which rodents are housed affects the development of morphine
      dependence. In this study, we used designer receptors exclusively activated by
      designer drugs to artificially increase or decrease the activity of peripheral
      dorsal root ganglia sensory neurons expressing the G-protein-coupled receptor
      MRGPRB4. This is because sensory MRGPRB4-expressing neurons were shown to
      specifically detect the sensation of massage-like stroking resulting from social
      grooming, which is an important affiliative social behavior in the rodent.
      Blocking the sensation of social grooming in morphine-treated mice housed with
      drug-naive mice (i.e. morphine cage mates) significantly increased the display of
      jumping behavior in morphine-withdrawn animals. Activating the sensation of
      social grooming in morphine-treated animals housed solely with other morphine
      treated animals (i.e. morphine only) did not significantly alter the display of
      jumping behavior in morphine-withdrawn animals. Repetitive jumping behaviors have
      been shown to correlate with morphine dependence. Thus, this study showed a role
      of social grooming in the protective effect of being housed with drug-naive mice
      on the development of morphine dependence. It further confirms a role of social
      support in the development of substance use problems.

PMID- 29049084
TI  - Exploration of Portal Activation by Patients in a Healthcare System.
AB  - A study of patient portal utilization was conducted at a not-for-profit
      healthcare system in Northern Virginia. The healthcare system serves more than 2
      million people each year. The encounters with the portal included 461 700
      different patients occurring between July 2014 and June 2015. Univariate analysis
      and multivariable logistic regression indicated associations between patient
      portal activation and predictive factors. Multiple findings emerged: patient
      portal activation was greater for English-speaking patients; differences in
      portal activation were observed by patient age; and patients who had an
      identified primary care provider were more likely to use the portal. The
      implications were that patients who have limited English skills and have economic
      challenges may be less engaged. This review demonstrates the importance of
      understanding the population using a patient portal and provides insight for
      future development on how to engage patients to interact with their providers
      through the portals.

PMID- 29049086
TI  - Editorial: myeloid biology issue 2018.

PMID- 29049083
TI  - Ketamine and pharmacological imaging: use of functional magnetic resonance
      imaging to evaluate mechanisms of action.
AB  - Ketamine has been used as a pharmacological model for schizophrenia as
      subanesthetic infusions have been shown to produce temporary schizophrenia-like
      symptoms in healthy humans. More recently, ketamine has emerged as a potential
      treatment for multiple psychiatric disorders, including treatment-resistant
      depression and suicidal ideation. However, the mechanisms underlying both the
      psychotomimetic and the therapeutic effects of ketamine remain poorly understood.
      This review provides an overview of what is known of the neural mechanisms
      underlying the effects of ketamine and details what functional MRI studies have
      yielded at a systems level focused on brain circuitry. Multiple analytic
      approaches show that ketamine exerts robust and consistent effects at the whole
      brain level. These effects are highly conserved across human and nonhuman
      primates, validating the use of nonhuman primate models for further
      investigations with ketamine. Regional analysis of brain functional connectivity
      suggests that the therapeutic potential of ketamine may be derived from a
      strengthening of executive control circuitry, making it an intriguing candidate
      for the treatment of drug abuse. There are still important questions about the
      mechanism of action and the therapeutic potential of ketamine that can be
      addressed using appropriate functional neuroimaging techniques.

PMID- 29049085
TI  - Experience and Compliance With Scanning Vaccines' Two-Dimensional Barcodes to
      Record Data.
AB  - Automated population of data into health information system fields offers the
      potential to increase efficiencies and save time. Increasingly, as two
      dimensional barcoded vaccine products and barcode scanning technology become more
      widely available, manual recording of vaccine data can be reduced. This
      evaluation explores how often two-dimensional barcodes on vaccine vials and
      syringes were scanned and the perceived benefits and challenges reported by
      vaccine providers. Eighty-two facilities that administer vaccines completed the
      evaluation. Twenty-seven of those facilities provided records from vaccines
      administered between July 2014 and January 2015. Among the 63 179 two-dimensional
      barcoded vaccine administrations recorded, 12 408 (19%) were scanned. We received
      116 user surveys from 63 facilities; using content analysis, we identified
      perceived benefits of scanning, workflow challenges, scanning challenges, and
      other challenges. The findings of this evaluation can guide health information
      system developers, vaccine manufacturers, and vaccine providers on how to remove
      potential barriers to using two-dimensional barcode scanning.

PMID- 29049087
TI  - Raising Mean Arterial Pressure Alone Restores 20% of Intraoperative
      Neuromonitoring Losses.
AB  - STUDY DESIGN: Multicenter prospective. OBJECTIVE: To assess the effect of
      intraoperative interventions in restoring intraoperative neuromonitoring (IONM)
      signals in pediatric spine surgery. SUMMARY OF BACKGROUND DATA: No prior studies
      have prospectively examined the rate of return of IONM signals by increasing
      blood pressure (BP) alone. METHODS: Patients undergoing posterior spinal
      deformity surgery were enrolled at their preoperative appointment. Surgeons
      completed an intraoperative data form on patients who experienced an IONM change
      defined as a 50% or greater decrease in either transcranial motor evoked
      potentials or somatosensory evoked potentials. RESULTS: Four hundred fifty two
      patients were enrolled with 30 (7%) having IONM change. Thirty patients met
      inclusion criteria (mean age, 12 yrs, range, 5-19) and had the following
      diagnoses: idiopathic scoliosis (43%), neuromuscular scoliosis (13%), congenital
      scoliosis (10%), early onset scoliosis (7%), and other (27%). 20% (6/30) had
      return of signals due to an increase in BP alone with no other interventions
      (mean arterial pressure [MAP] increased from mean of 68 [range, 58-76] to 86 mmHg
      [range, 75-95]). Signals returned to baseline after mean of 16 minutes (range, 2
      45). In 60% of patients (18/30), MAP was raised from a mean of 72 mmHg (range, 55
      84) to 86 mmHg (range, 75-100) in conjunction with other interventions and had
      mean return of signals in 37 minutes (range, 8-210). Six (20%) of patients had
      signals return to baseline after a mean of 6 minutes (range, 3-13) in which MAP
      did not change appreciably. All patients had return of signals at the conclusion
      of the procedure with one patient having postoperative neurological sequale.
      CONCLUSION: In this prospective study of 452 pediatric spinal deformity
      surgeries, raising MAPs above 85 mmHg should be considered the first step in
      response to IONM signal changes, as this alone was successful in 20% of patients
      without sacrificing deformity correction. LEVEL OF EVIDENCE: 2.

PMID- 29049088
TI  - Recall Bias in Low Back Pain Among Workers: Effects of Recall Period and
      Individual and Work-Related Factors.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: The aim of the present study
      was first to compare monthly measurements of low back pain (LBP) with quarterly
      and yearly retrospective measurements of LBP, and second to investigate possible
      bias effects for recall bias of LBP. SUMMARY OF BACKGROUND DATA: LBP is a
      subjective experience often measured by a single rating of recalled pain over a
      certain time interval. However, retrospectively reported pain may be subject to
      recall bias. METHODS: The agreement between monthly measurements of LBP and
      quarterly and yearly retrospective measurements of LBP was evaluated by Spearman
      rank order correlation coefficients, intraclass correlation coefficients, and
      Bland-Altman plots. Bias effects for recall bias were investigated by a linear
      regression model. RESULTS: There were no statistical significant differences in
      mean values of monthly measurements of LBP compared with quarterly and yearly
      retrospective measurements of LBP on a group level. However, the Bland-Altman
      plots revealed that within individuals, the difference between monthly
      measurements of LBP and quarterly and yearly retrospective measurements of LBP
      was highly variable. For both quarterly and yearly recall, social support from
      colleagues and average LBP days were significantly associated with the recall
      bias. CONCLUSION: The agreement of pain recall among workers in the current study
      seems to be good on a group level, but both between and within individuals, the
      difference between monthly and quarterly and yearly retrospective measurements
      was quite high. Factors that impacted the recall bias were social support from
      colleagues and average LBP days over the recall period. LEVEL OF EVIDENCE: 3.

PMID- 29049089
TI  - Coronary endarterectomy to facilitate bypass surgery for patients with extensive
      stenting of the left anterior descending artery.

PMID- 29049090
TI  - Pharmacomechanical Thrombolysis for Deep Vein Thrombosis in May-Thurner Syndrome.
AB  - OBJECTIVE: Patients with May-Thurner syndrome presenting with acute deep vein
      thrombosis benefit from early lysis of clot and endovascular treatment. We
      evaluated the outcome of patients with May-Thurner syndrome who presented with
      deep vein thrombosis, managed with pharmacomechanical thrombolysis as the primary
      mode of intervention, in combination with angioplasty and stent placement.
      METHODS: We reviewed all patients with May-Thurner syndrome managed in our
      institution between January 2009 to December 2015. Patency rate and
      postthrombotic syndrome were evaluated as primary end points. RESULTS: A total of
      seven patients (6 females, 1 male) with a mean +/- SD age of 48 +/- 17 years and
      mean +/- SD body mass index of 29.64 +/- 7.25 kg/m were identified. Six patients
      presented with acute deep vein thrombosis and one presented with chronic venous
      insufficiency. Five patients underwent pharmacomechanical thrombolysis (TRELLIS
      and altepase) with concomitant stenting of the common iliac vein, one had only
      angioplasty with stent placement, and one had only pharmacomechanical
      thrombolysis. Median time from presentation to pharmacomechanical thrombolysis
      was 4 days (range = 1-9). Patency rate and postthrombotic syndrome at 12 months
      were 100% and 0%, respectively. No patient experienced major bleeding or
      pulmonary embolism. The median length of stay was 3 days (range = 0-4). There was
      no mortality associated with the procedure. The mean +/- SD follow-up was 26 +/-
      15 months. CONCLUSIONS: In patients with May-Thurner syndrome, pharmacomechanical
      thrombolysis is an effective approach for the management of acute deep vein
      thrombosis, decreasing thrombus burden, and long-term postthrombotic syndrome
      when used in conjunction with stenting.

PMID- 29049091
TI  - Tumor Microenvironment and Models of Ovarian Cancer: The 11th Biennial Rivkin
      Center Ovarian Cancer Research Symposium.
AB  - OBJECTIVE: The aim of this study was to review the latest research advances on
      the topics of the ovarian cancer tumor microenvironment and models of ovarian
      cancer. METHODS: In September 2016, a symposium of the leaders in the field of
      ovarian cancer research was convened to present and discuss current advances and
      future directions in ovarian cancer research. RESULTS: One session was dedicated
      to Tumor Microenvironment and Models of Ovarian Cancer, and included a keynote
      presentation from Anil Sood, MD, and an invited oral presentation from David
      Huntsman, MD. Eight additional oral presentations were selected from abstract
      submissions. Twenty-nine abstracts were presented in poster format and can be
      grouped into the categories of stromal cells in the microenvironment, immune
      cells in the microenvironment, epithelial-mesenchymal transition and metastasis,
      metabolomics, and model systems including spheroids, murine models, and other
      animal models. CONCLUSIONS: Rapid advances continue in our understanding of the
      influence of the tumor microenvironment on ovarian cancer progression and
      metastasis. Vascular endothelial cells, stromal cells, and immune cells all
      modulate epithelial tumor cell biology and therefore serve as potential targets
      for improved treatment responses either in conjunction with or instead of current
      treatment modalities. Characterization of the underlying genetic alterations in
      both the tumor cells and surrounding microenvironment cells enhances our
      understanding of tumor biology. Model systems including both in vitro and in vivo
      approaches allow novel advances. Technological advances including sequencing
      strategies, use of mass spectrometry for metabolomics and other studies, and
      bioengineering approaches all complement conventional methodologies to push
      forward our understanding and ultimately the treatment of ovarian cancer.

PMID- 29049092
TI  - A Quiet Firehouse: Reducing Environmental Stimuli Among Professional On-Duty
      Firefighters.
AB  - OBJECTIVE: Firehouse alarms are so loud that they cause a systemic response,
      similar to the flight-or-flight response. The purpose of the study was to reduce
      firehouse environmental stimuli to improve sleep quality and, thus, reduce
      cardiac burden. METHODS: The intervention included restricted unnecessary fire
      alarms, reduced light levels, and regulated temperature in the bunkroom. RESULTS:
      Among 24 firefighters, 11 completed the matched post-assessment. Six weeks after
      implementing the interventions, measures revealed the average lux level dropped
      from 0.75 to 0.19 lux, P < 0.05, and the presence of elevated blood pressure
      reduced from 86% to 15%, P < 0.05. CONCLUSION: Results support that reducing
      environmental stimuli in firehouses reduces blood pressure, which is much easier
      than targeting behavior change. RECOMMENDATIONS: On the basis of this pilot
      study, the practice of routinely activating unnecessary fire alarms in firehouse
      bunkrooms should be discouraged.

PMID- 29049094
TI  - Validation of the AVITA BPM64 upper-arm blood pressure monitor for home blood
      pressure monitoring according to the European Society of Hypertension
      International Protocol revision 2010.
AB  - OBJECTIVE: The aim of this study was to evaluate the accuracy of the automated
      oscillometric upper arm blood pressure (BP) monitor AVITA BPM64 for home BP
      monitoring according to the International Protocol of the European Society of
      Hypertension revision 2010. METHODS: Systolic and diastolic BPs were measured
      sequentially in 33 adult Chinese (14 women, mean age 47.0 years) using a mercury
      sphygmomanometer (two observers) and the AVITA BPM64 device (one supervisor). A
      total of 99 pairs of comparisons were obtained from 33 participants for judgments
      in two parts with three grading phases. RESULTS: The AVITA BPM64 device achieved
      the targets in part 1 of the validation study. The number of absolute differences
      between device and observers within 5, 10, and 15 mmHg was 91/99, 98/99, and
      98/99, respectively, for systolic BP and 92/99, 99/99, and 99/99, respectively,
      for diastolic BP. The device also fulfilled the criteria in part 2 of the
      validation study. Thirty-two participants for both systolic and diastolic BP had
      at least two of the three device-observer differences within 5 mmHg (required
      >=24). Only one participant for systolic BP had all three device-observer
      comparisons greater than 5 mmHg. CONCLUSION: The AVITA upper arm BP monitor BPM64
      has passed the requirements of the International Protocol revision 2010, and
      hence can be recommended for home use in adults.

PMID- 29049093
TI  - Association of Metformin Use and Survival Outcome in Women With Cervical Cancer.
AB  - OBJECTIVE: Although preclinical studies suggest possible antitumor effects of
      metformin against cervical cancer, there is currently a lack of clinical data
      examining the association of metformin use and survival in women with cervical
      cancer. The aim of this study was to examine survival of women with cervical
      cancer who were receiving metformin. METHODS: This is a retrospective study
      examining consecutive cases of stages I to IV cervical cancer between 2000 and
      2014. Patient demographics, medication use, tumor characteristics, treatment
      patterns, and survival outcomes were correlated to metformin use. RESULTS: There
      were 70 (8.9%; 95% confidence interval [CI], 6.9-10.9) metformin users and 715
      nonusers identified for the analysis. Median follow-up time was 22.6 months.
      Recurrence/progression of disease and death due to cervical cancer were observed
      in 236 and 163 cases, respectively. Metformin users were more likely to be older,
      hypertensive, diabetic, and dyslipidemic compared with nonusers (all, P < 0.05).
      On univariate analysis, metformin users and nonusers had similar progression-free
      survival (PFS) (5-year rates; 57.3% vs 61.8%; P = 0.82) and cervical cancer
      specific overall survival (71.7% vs 70.7%; P = 0.86). After adjusting for patient
      demographics and tumor characteristics, metformin use was not associated with PFS
      (adjusted hazards ratio, 1.11; 95% CI, 0.70-1.74; P = 0.67) or cervical cancer
      specific overall survival (adjusted hazards ratio, 0.91; 95% CI, 0.52-1.60; P =
      0.75). Among 478 women who received whole pelvic radiotherapy, metformin use was
      not associated with PFS (P = 0.93) or cervical cancer-specific overall survival
      (P = 0.32). CONCLUSIONS: In this study population, metformin use was not
      associated with survival of women with cervical cancer.

PMID- 29049096
TI  - The Effect of Tackler Technique on Head Injury Assessment Risk in Elite Rugby
      Union.
AB  - PURPOSE: This study aimed to use match video evidence of tackles in elite-level
      rugby union to identify tackler proficiency characteristics, for both lower body
      and upper body tackles, that result in head injury assessments (HIA) for the
      tackler. METHODS: A review of international rugby union matches (2013-2017) and
      Pro 12/European Rugby Champions Cup matches (2014-2017) from a professional rugby
      union club was conducted. HIA (n = 74) and non-HIA tackles (n = 233) were
      categorized as either front-on or side-on upper body or lower body tackles and
      were scored for tackling proficiency characteristics. A chi-square test (P <
      0.05) and phi and Cramer's V were calculated to compare HIA and non-HIA tackling
      proficiency characteristics. RESULTS: In both front- and side-on upper body and
      lower body tackles, "head up and forward/face up" and "head placement on correct
      side of ball carrier" were identified as having a lower propensity to result in
      an HIA for the tackler. For both front-on and side-on upper body tackles,
      "identify/track ball carrier onto shoulder" and "shortening steps" were
      identified. In addition, "straight back, centre of gravity forward of support
      base" and "identify/track ball carrier onto shoulder" were identified for front
      on and side-on lower body tackles, respectively. CONCLUSIONS: This study
      identified tackle characteristics that had a lower propensity to result in an HIA
      for the tackler in both front-on and side-on upper body and lower body tackles.

PMID- 29049097
TI  - Low serum uric acid levels in patients with acute central nervous system viral
      infections.
AB  - Most acute central nervous system (CNS) viral infections lead to either
      encephalitis or meningitis. Many neurotropic viruses may cause CNS dysfunctions
      through various mechanisms including oxidative stress. Serum uric acid (SUA)
      levels, which are associated with oxidative stress and antioxidant status, are
      reduced in patients with various neurological disorders, including multiple
      sclerosis. We investigated the possible correlation between SUA levels and
      clinical disease status in patients with acute CNS viral infections. We measured
      SUA concentrations in 336 individuals, including 179 healthy individuals and 157
      patients with acute CNS viral infections. We found that the patients had lower
      SUA levels than the healthy individuals did irrespective of sex. Effective
      therapy significantly increased SUA levels. The patients' SUA levels were
      correlated inversely with outcomes as measured with the Glasgow Outcome Scale.
      SUA levels may be a biomarker for predicting treatment outcomes and prognoses for
      patients with acute CNS viral infections with inflammatory components.

PMID- 29049098
TI  - Distribution of Elastic Fibers in the Lacrimal Sac and Nasolacrimal Duct of
      Japanese Cadavers.
AB  - PURPOSE: To investigate the distribution of elastic fibers in lacrimal sac and
      nasolacrimal duct of Japanese cadavers. METHODS: We examined 8 lacrimal sacs and
      nasolacrimal ducts of 7 Japanese cadavers (4 right sides, 4 left sides; 3 males,
      4 females; average age of 89 years at death) that were preserved with 10%
      buffered formalin. The harvested specimens were transversely sectioned. All
      specimens were stained with Elastica van Gieson. Micrographs were taken, and then
      converted to white and black images, and the elastic fiber density of 4 locations
      (middle and upper levels of lacrimal sac, and middle and lower levels of
      nasolacrimal duct) was compared. RESULTS: Elastic fibers showed greater
      distribution in the lamina propria, compared with the submucosal tissue, at all
      locations (p < 0.001). Elastic fiber density within the lamina propria at the
      middle lacrimal sac level (13.5% +/- 4.3%) was similar to the density observed at
      the upper lacrimal sac level (13.2% +/- 2.3%, p = 0.87) and the lower
      nasolacrimal duct level (17.8% +/- 6.0%, p = 0.088), but was significantly
      greater than the density observed at the middle nasolacrimal duct level (9.5% +/-
      3.8%, p = 0.0001). CONCLUSIONS: Elastic fibers in the lacrimal sac and
      nasolacrimal duct are primarily distributed in the lamina propria, with a greater
      density at the upper and middle lacrimal sac levels, and at the lower
      nasolacrimal duct level, compared with the middle nasolacrimal duct level. This
      distribution of elastic fibers likely reflects the magnitude of mechanical stress
      within the lacrimal drainage system.

PMID- 29049100
TI  - Models of borderline personality disorder: recent advances and new perspectives.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the most relevant
      conceptual models of borderline personality disorder (BPD), with a focus on
      recent developments in this area. RECENT FINDINGS: Several conceptual models have
      been proposed with the aim of better understanding BPD: the borderline
      personality organization, emotion dysregulation, reflective (mentalization)
      dysfunction, interpersonal hypersensitivity and hyperbolic temperament models.
      These models have all been supported to some extent and their common components
      include disorganized attachment and traumatic early experiences, emotion
      dysregulation, interpersonal sensitivity and difficulties with social cognition.
      An attempt to integrate some components of the conceptual models of BPD has
      resulted in an emerging new perspective, the interpersonal dysphoria model, which
      emphasizes dysphoria as an overarching phenomenon that connects the dispositional
      and situational aspects of BPD. SUMMARY: Various conceptual models have expanded
      our understanding of BPD, but it appears that further development entails
      theoretical integration. More research is needed to better understand
      interactions between various components of BPD, including the situational factors
      that activate symptoms of BPD. This will help develop therapeutic approaches that
      are more tailored to the heterogeneous psychopathology of BPD.

PMID- 29049099
TI  - Spontaneous Rupture of Lacrimal Gland Pleomorphic Adenoma: Pivotal Role in
      Masquerading Orbital Cellulitis.
AB  - The authors aim to report a 68-year-old patient presenting with acute swelling
      and redness of orbital area diagnosed initially as orbital cellulitis. Surgical
      excision was decided based on clinical and imaging findings with the diagnosis of
      pleomorphic adenoma of the lacrimal gland. Lacrimal gland pleomorphic adenoma
      usually presents with painless gradual swelling of upper eyelid. In an
      exceptionally rare circumstance, this case showed acute orbital inflammation, and
      imaging findings of orbital inflammation mostly focused around the cystic space
      of the lacrimal gland tumor. Histologic evaluation confirmed a ruptured cystic
      space of pleomorphic adenoma with foreign body-type inflammatory reaction. The
      authors propose spontaneous rupture of cystic space in the lacrimal gland
      pleomorphic adenoma as underlying mechanism for acute presentation of this tumor.
      Imaging and clinical characteristics and also prognostic implication of this
      phenomenon are discussed.

PMID- 29049102
TI  - Unraveling the Mystery of THC: Cannabinoids and Neuropathic Pain.

PMID- 29049101
TI  - Molecular Targets for Pain Management: More Than Just Mu.

PMID- 29049103
TI  - "Houston, We Have a Problem!": The Role of the Anesthesiologist in the Current
      Opioid Epidemic.

PMID- 29049104
TI  - The Opioid Crisis in the United States: Chronic Pain Physicians Are the Answer,
      Not the Cause.

PMID- 29049105
TI  - Themed Issue on the Opioid Epidemic: What Have We Learned? Where Do We Go From
      Here?

PMID- 29049106
TI  - Do Not Resuscitate and the Surgical Patient: Not a Contradiction in Terms.

PMID- 29049107
TI  - Venovenous Bypass Associated With Acute Kidney Injury Prevention in Liver
      Transplantation: An Ode to the Retrospective Data Researcher.

PMID- 29049108
TI  - The Perioperative Surgical Home Is Not Just a Name.

PMID- 29049109
TI  - Tracking Speckles: Overcoming Conventions to Evaluate Right Ventricular Function.

PMID- 29049110
TI  - Evidence for the Efficacy of Systemic Opioid-Sparing Analgesics in Pediatric
      Surgical Populations: A Systematic Review.
AB  - While a large number of studies has examined the efficacy of opioid-sparing
      analgesics in adult surgical populations, fewer studies are available to guide
      postoperative pain treatment in pediatric patients. We systematically reviewed
      available publications on the use of systemic nonopioid agents for postoperative
      analgesia in pediatric surgical populations. A comprehensive literature search
      identified meta-analyses and randomized controlled trials (RCTs) assessing the
      effects of systemic, nonopioid agents on postoperative narcotic requirements or
      pain scores in pediatric surgical populations. If a meta-analysis was located, we
      summarized its results and any RCTs published after it. We located and reviewed
      11 acetaminophen RCTs, 1 nonsteroidal anti-inflammatory drug (NSAID) meta
      analysis, 2 NSAID RCTs, 1 dexamethasone meta-analysis, 3 dexamethasone RCTs, 2
      ketamine meta-analyses, 5 ketamine RCTs, 2 gabapentin RCTs, 1 clonidine meta
      analysis, 3 magnesium RCTs, 2 dexmedetomidine meta-analyses, and 1
      dextromethorphan RCT. No meta-analyses or RCTs were found assessing the
      perioperative efficacy of intravenous lidocaine, amantadine, pregabalin, esmolol,
      or caffeine in pediatric surgical patients. The available evidence is limited,
      but suggests that perioperative acetaminophen, NSAIDs, dexamethasone, ketamine,
      clonidine, and dexmedetomidine may decrease postoperative pain and opioid
      consumption in some pediatric surgical populations. Not enough, or no, data exist
      from which to draw conclusions on the perioperative use of gabapentin, magnesium,
      dextromethorphan, lidocaine, amantadine, pregabalin, esmolol, and caffeine in
      pediatric surgical patients. Further pharmacokinetic and pharmacodynamics studies
      to establish both the clinical benefit and efficacy of nonopioid analgesia in
      pediatric populations are needed.

PMID- 29049111
TI  - Risk Management for Opioid Prescribing in the Treatment of Patients With Pain
      From Cancer or Terminal Illness: Inadvertent Oversight or Taboo?
AB  - As the United States experiences an epidemic of prescription drug abuse, and
      guidelines on safe practices in prescribing opioids in chronic pain have
      subsequently emerged from professional organizations and governmental agencies,
      limited guidance exists for prescribers of opioids to treat pain in patients with
      cancer or terminal illness. Patients with active cancer or terminal illness often
      have pain and are frequently prescribed opioids and other controlled substances.
      Current studies suggest that patients with cancer have similar rates of risk for
      misuse, abuse, and addiction as the general public. Moreover, palliative care and
      hospice programs appear poorly prepared for assessing or managing patients with
      aberrant behaviors or evidence of drug abuse. Further research and professional
      consensus are needed to help address the challenges associated with misuse,
      abuse, and addiction in patients with cancer and terminal illness.

PMID- 29049112
TI  - America's Opioid Epidemic: Supply and Demand Considerations.
AB  - America is in the midst of an opioid epidemic characterized by aggressive
      prescribing practices, highly prevalent opioid misuse, and rising rates of
      prescription and illicit opioid overdose-related deaths. Medical and lay public
      sentiment have become more cautious with respect to prescription opioid use in
      the past few years, but a comprehensive strategy to reduce our reliance on
      prescription opioids is lacking. Addressing this epidemic through reductions in
      unnecessary access to these drugs while implementing measures to reduce demand
      will be important components of any comprehensive solution. Key supply-side
      measures include avoiding overprescribing, reducing diversion, and discouraging
      misuse through changes in drug formulations. Important demand-side measures
      center around educating patients and clinicians regarding the pitfalls of opioid
      overuse and methods to avoid unnecessary exposure to these drugs.
      Anesthesiologists, by virtue of their expertise in the use of these drugs and
      their position in guiding opioid use around the time of surgery, have important
      roles to play in reducing patient exposure to opioids and providing education
      about appropriate use. Aside from the many immediate steps that can be taken,
      clinical and basic research directed at understanding the interaction between
      pain and opioid misuse is critical to identifying the optimal use of these
      powerful pain relievers in clinical practice.

PMID- 29049113
TI  - The US Opioid Crisis: Current Federal and State Legal Issues.
AB  - The United States is in the midst of a devastating opioid misuse epidemic leading
      to over 33,000 deaths per year from both prescription and illegal opioids.
      Roughly half of these deaths are attributable to prescription opioids. Federal
      and state governments have only recently begun to grasp the magnitude of this
      public health crisis. In 2016, the Centers for Disease Control and Prevention
      released their Guidelines for Prescribing Opioids for Chronic Pain. While not
      comprehensive in scope, these guidelines attempt to control and regulate opioid
      prescribing. Other federal agencies involved with the federal regulatory effort
      include the Food and Drug Administration (FDA), the Drug Enforcement Agency
      (DEA), and the Department of Justice. Each federal agency has a unique role in
      helping to stem the burgeoning opioid misuse epidemic. The DEA, working with the
      Department of Justice, has enforcement power to prosecute pill mills and
      physicians for illegal prescribing. The DEA could also implement use of
      prescription drug monitoring programs (PDMPs), currently administered at the
      state level, and use of electronic prescribing for schedule II and III
      medications. The FDA has authority to approve new and safer formulations of
      immediate- and long-acting opioid medications. More importantly, the FDA can also
      ask pharmaceutical companies to cease manufacturing a drug. Additionally, state
      agencies play a critical role in reducing overdose deaths, protecting the public
      safety, and promoting the medically appropriate treatment of pain. One of the
      states' primary roles is the regulation of practice of medicine and the insurance
      industry within their borders. Utilizing this authority, states can both educate
      physicians about the dangers of opioids and make physician licensure dependent on
      registering and using PDMPs when prescribing controlled substances. Almost every
      state has implemented a PDMP to some degree; however, in addition to mandating
      their use, increased interstate sharing of prescription information would greatly
      improve PDMPs' effectiveness. Further, states have the flexibility to promote
      innovative interventions to reduce harm such as legislation allowing naloxone
      access without a prescription. While relatively new, these types of laws have
      allowed first responders, patients, and families access to a lifesaving drug.
      Finally, states are at the forefront of litigation against pharmaceutical
      manufacturers. This approach is described as analogous to the initial steps in
      fighting tobacco companies. In addition to fighting for dollars to support drug
      treatment programs and education efforts, states are pursuing these lawsuits as a
      means of holding pharmaceutical companies accountable for misleading marketing of
      a dangerous product.

PMID- 29049115
TI  - An Evidence-Based Approach to the Prescription Opioid Epidemic in Orthopedic
      Surgery.
AB  - Orthopedic surgery is associated with significant perioperative pain. Providing
      adequate analgesia is a critical component of patient care and opioids play a
      vital role in the acute postoperative setting. However, opioid prescribing for
      patients undergoing orthopedic procedures has recently been identified as a major
      contributor to the current opioid epidemic. As opioid usage and related morbidity
      and mortality continue to rise nationwide, opioid-prescribing practices are under
      increased scrutiny. Here, we update the evidence base and recommendations behind
      a set of interventions developed at the Hospital for Special Surgery to address
      the national epidemic at the local level. The main components of our program
      include (1) guidelines for managing patients who are opioid tolerant and/or have
      a substance abuse disorder; (2) education programs for patients, emphasizing the
      role of opioids in recovery after elective orthopedic surgery; (3) education
      programs for prescribers of controlled substances, including clinical and
      regulatory aspects; (4) the development of surgery-specific prescribing
      recommendations for opioid-naive patients; and (5) mechanisms to modify
      prescribing habits to limit unnecessary prescribing of controlled substances.

PMID- 29049118
TI  - Risk Factors for Opioid-Use Disorder and Overdose.
AB  - Opioid analgesics are recognized as a legitimate medical therapy for selected
      patients with severe chronic pain that does not respond to other therapies.
      However, opioids are associated with risks for patients and society that include
      misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success
      depends on proper candidate selection, assessment before administering opioid
      therapy, and close monitoring throughout the course of treatment. Risk assessment
      and prevention include knowledge of patient factors that may contribute to
      misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for
      opioid misuse or addiction include past or current substance abuse, untreated
      psychiatric disorders, younger age, and social or family environments that
      encourage misuse. Opioid mortality prevalence is higher in people who are middle
      aged and have substance abuse and psychiatric comorbidities. Suicides are
      probably undercounted or frequently misclassified in reports of opioid-related
      poisoning deaths. Greater understanding and better assessment are needed of the
      risk associated with suicide risk in patients with pain. Clinical tools and an
      evolving evidence base are available to assist clinicians with identifying
      patients whose risk factors put them at risk for adverse outcomes with opioids.

PMID- 29049114
TI  - Alternatives to Opioids in the Pharmacologic Management of Chronic Pain
      Syndromes: A Narrative Review of Randomized, Controlled, and Blinded Clinical
      Trials.
AB  - Chronic pain exerts a tremendous burden on individuals and societies. If one
      views chronic pain as a single disease entity, then it is the most common and
      costly medical condition. At present, medical professionals who treat patients in
      chronic pain are recommended to provide comprehensive and multidisciplinary
      treatments, which may include pharmacotherapy. Many providers use nonopioid
      medications to treat chronic pain; however, for some patients, opioid analgesics
      are the exclusive treatment of chronic pain. However, there is currently an
      epidemic of opioid use in the United States, and recent guidelines from the
      Centers for Disease Control (CDC) have recommended that the use of opioids for
      nonmalignant chronic pain be used only in certain circumstances. The goal of this
      review was to report the current body of evidence-based medicine gained from
      prospective, randomized-controlled, blinded studies on the use of nonopioid
      analgesics for the most common noncancer chronic pain conditions. A total of 9566
      studies were obtained during literature searches, and 271 of these met inclusion
      for this review. Overall, while many nonopioid analgesics have been found to be
      effective in reducing pain for many chronic pain conditions, it is evident that
      the number of high-quality studies is lacking, and the effect sizes noted in many
      studies are not considered to be clinically significant despite statistical
      significance. More research is needed to determine effective and mechanism-based
      treatments for the chronic pain syndromes discussed in this review. Utilization
      of rigorous and homogeneous research methodology would likely allow for better
      consistency and reproducibility, which is of utmost importance in guiding
      evidence-based care.

PMID- 29049119
TI  - A Review of Opioid-Sparing Modalities in Perioperative Pain Management: Methods
      to Decrease Opioid Use Postoperatively.
AB  - There is an epidemic of opioid use, abuse, and misuse in the United States, which
      results in significant morbidity and mortality. It may be difficult to reduce
      perioperative opioid use given known acute surgical trauma and resultant pain;
      however, the discrete and often limited nature of postoperative pain also may
      make management easier in part by utilizing nonopioid modalities, such as
      regional anesthesia/analgesia, and multimodal analgesia, which may decrease the
      need for powerful opioids. This article reviews the relevant literature
      describing the use of adjunct medications, regional anesthesia and analgesic
      techniques, and regional block additives in the context of providing adequate
      pain control while lessening opioid use.

PMID- 29049117
TI  - Chronic Opioid Use After Surgery: Implications for Perioperative Management in
      the Face of the Opioid Epidemic.
AB  - Physicians, policymakers, and researchers are increasingly focused on finding
      ways to decrease opioid use and overdose in the United States both of which have
      sharply increased over the past decade. While many efforts are focused on the
      management of chronic pain, the use of opioids in surgical patients presents a
      particularly challenging problem requiring clinicians to balance 2 competing
      interests: managing acute pain in the immediate postoperative period and
      minimizing the risks of persistent opioid use after the surgery. Finding ways to
      minimize this risk is particularly salient in light of a growing literature
      suggesting that postsurgical patients are at increased risk for chronic opioid
      use. The perioperative care team, including surgeons and anesthesiologists, is
      poised to develop clinical- and systems-based interventions aimed at providing
      pain relief in the immediate postoperative period while also reducing the risks
      of opioid use longer term. In this paper, we discuss the consequences of chronic
      opioid use after surgery and present an analysis of the extent to which surgery
      has been associated with chronic opioid use. We follow with a discussion of the
      risk factors that are associated with chronic opioid use after surgery and
      proceed with an analysis of the extent to which opioid-sparing perioperative
      interventions (eg, nerve blockade) have been shown to reduce the risk of chronic
      opioid use after surgery. We then conclude with a discussion of future research
      directions.

PMID- 29049120
TI  - A Contemporary Medicolegal Analysis of Outpatient Medication Management in
      Chronic Pain.
AB  - BACKGROUND: Opioids are frequently used in chronic pain management but are
      associated with significant morbidity and mortality in some patient populations.
      An important avenue for identifying complications-including serious or rare
      complications-is the study of closed malpractice claims. The present study is
      intended to complement the existing closed claims literature by drawing on claims
      from a more recent timeframe through a partnership with a large malpractice
      carrier, the Controlled Risk Insurance Company (CRICO). The goal of this study
      was to identify patient medical comorbidities and aberrant drug behaviors, as
      well as prescriber practices associated with patient injury and malpractice
      claims. Another objective was to identify claims most likely to result in
      payments and use this information to propose a strategy for reducing medicolegal
      risk. METHODS: The CRICO Strategies Comparative Benchmarking System is a database
      of claims drawing from >350,000 malpractice claims from Harvard-affiliated
      institutions and >400 other academic and community institutions across the United
      States. This database was queried for closed claims from January 1, 2009, to
      December 31, 2013, and identified 37 cases concerning noninterventional,
      outpatient chronic pain management. Each file consisted of a narrative summary,
      including expert witness testimony, as well as coded fields for patient
      demographics, medical comorbidities, the alleged damaging event, the alleged
      injurious outcome, the total financial amount incurred, and more. We performed an
      analysis using these claim files. RESULTS: The mean patient age was 43.5 years,
      with men representing 59.5% of cases. Payments were made in 27% of cases, with a
      median payment of $72,500 and a range of $7500-$687,500. The majority of cases
      related to degenerative joint disease of the spine and failed back surgery
      syndrome; no patients in this series received treatment of malignant pain.
      Approximately half (49%) of cases involved a patient death. The use of long
      acting opioids and medical conditions affecting the cardiac and pulmonary systems
      were more closely associated with death than with other outcomes. The nonpain
      medical conditions present in this analysis included obesity, obstructive sleep
      apnea, chronic obstructive pulmonary disease, hypertension, and coronary artery
      disease. Other claims ranged from alleged addiction to opioids from improper
      prescribing to alleged abandonment with withdrawal of care. The CRICO analysis
      suggested that patient behavior contributed to over half of these claims, whereas
      deficits in clinical judgment contributed to approximately 40% of the claims
      filed. CONCLUSIONS: Claims related to outpatient medication management in pain
      medicine are multifactorial, stemming from deficits in clinical judgment by
      physicians, noncooperation in care by patients, and poor clinical documentation.
      Minimization of both legal risk and patient harm can be achieved by carefully
      selecting patients for chronic opioid therapy and documenting compliance and
      improvement with the treatment plan. Medical comorbidities such as obstructive
      sleep apnea and the use of long-acting opioids may be particularly dangerous.
      Continuing physician education on the safest and most effective approaches to
      manage these medications in everyday practice will lead to both improved legal
      security and patient safety.

PMID- 29049116
TI  - Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted
      Pain Therapeutics.
AB  - Opioids represent an efficacious therapeutic modality for some, but not all pain
      states. Singular reliance on opioid therapy for pain management has limitations,
      and abuse potential has deleterious consequences for patient and society. Our
      understanding of pain biology has yielded insights and opportunities for
      alternatives to conventional opioid agonists. The aim is to have efficacious
      therapies, with acceptable side effect profiles and minimal abuse potential,
      which is to say an absence of reinforcing activity in the absence of a pain
      state. The present work provides a nonexclusive overview of current drug targets
      and potential future directions of research and development. We discuss channel
      activators and blockers, including sodium channel blockers, potassium channel
      activators, and calcium channel blockers; glutamate receptor-targeted agents,
      including N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics
      targeted at gamma-aminobutyric acid, alpha2-adrenergic, and opioid receptors. We
      also considered antagonists of angiotensin 2 and Toll receptors and
      agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel
      targets considered are those focusing on lipid mediators and anti-inflammatory
      cytokines. Of interest is development of novel targeting strategies, which
      produce long-term alterations in pain signaling, including viral transfection and
      toxins. We consider issues in the development of druggable molecules, including
      preclinical screening. While there are examples of successful translation,
      mechanistically promising preclinical candidates may unexpectedly fail during
      clinical trials because the preclinical models may not recapitulate the
      particular human pain condition being addressed. Molecular target
      characterization can diminish the disconnect between preclinical and humans'
      targets, which should assist in developing nonaddictive analgesics.

PMID- 29049121
TI  - Opioids for the Treatment of Chronic Pain: Mistakes Made, Lessons Learned, and
      Future Directions.
AB  - An overreliance on opioids has impacted all types of pain management, making it
      undoubtedly a root cause of the "epidemic" of prescription opioid abuse in the
      United States. Yet, an examination of the statistics that led the US Centers for
      Disease Control and Prevention to declare that prescription opioid abuse had
      reached epidemic levels shows that the abuse occurrences and deaths are arising
      outside the hospital or hospice setting, which strongly implicates the outpatient
      use of opioids to treat chronic pain. Such abuse and related deaths are occurring
      in chronic pain patients themselves and also through diversion. Overprescribing
      to outpatients has afforded distressed and vulnerable individuals access to these
      highly addictive drugs. The focus of this article is on what we have learned
      since opioid treatment of chronic pain was first popularized at the end of the
      20th century and how this new information can guide chronic pain management in
      the future.

PMID- 29049122
TI  - Case Series of Successful Postoperative Pain Management in Buprenorphine
      Maintenance Therapy Patients.
AB  - Buprenorphine maintenance therapy patients frequently have severe postoperative
      pain due to buprenorphine-induced hyperalgesia and provider use of opioids with
      limited efficacy in the presence of buprenorphine. The authors report good-to
      excellent pain management in 4 obstetric patients using nonopioid analgesics,
      regional anesthesia, continuation of buprenorphine, and use of opioids with high
      MU receptor affinity.

PMID- 29049123
TI  - Impact of Enhanced Recovery After Surgery and Opioid-Free Anesthesia on Opioid
      Prescriptions at Discharge From the Hospital: A Historical-Prospective Study.
AB  - BACKGROUND: The United States is in the midst of an opioid epidemic, and opioid
      use disorder often begins with a prescription for acute pain. The perioperative
      period represents an important opportunity to prevent chronic opioid use, and
      recently there has been a paradigm shift toward implementation of enhanced
      recovery after surgery (ERAS) protocols that promote opioid-free and multimodal
      analgesia. The objective of this study was to assess the impact of an ERAS
      intervention for colorectal surgery on discharge opioid prescribing practices.
      METHODS: We conducted a historical-prospective quality improvement study of an
      ERAS protocol implemented for patients undergoing colorectal surgery with a focus
      on the opioid-free and multimodal analgesia components of the pathway. We
      compared patients undergoing colorectal surgery 1 year before implementation
      (June 15, 2015, to June 14, 2016) and 1 year after implementation (June 15, 2016,
      to June 14, 2017). RESULTS: Before the ERAS intervention, opioids at discharge
      were not significantly increasing (1% per month; 95% confidence interval [CI], 
      1% to 3%; P = .199). Immediately after the ERAS intervention, opioid
      prescriptions were not significantly lower (13%; 95% CI, -30% to 3%; P = .110).
      After the intervention, the rate of opioid prescriptions at discharge did not
      decrease significantly 1% (95% CI, -3% to 1%) compared to the pre-period rate (P
      = .399). Subgroup analysis showed that in patients with a combination of low
      discharge pain scores, no preoperative opioid use, and low morphine milligram
      equivalents consumption before discharge, the rate of discharge opioid
      prescription was 72% (95% CI, 61%-83%). CONCLUSIONS: This study is the first to
      report discharge opioid prescribing practices in an ERAS setting. Although an
      ERAS intervention for colorectal surgery led to an increase in opioid-free
      anesthesia and multimodal analgesia, we did not observe an impact on discharge
      opioid prescribing practices. The majority of patients were discharged with an
      opioid prescription, including those with a combination of low discharge pain
      scores, no preoperative opioid use, and low morphine milligram equivalents
      consumption before discharge. This observation in the setting of an ERAS pathway
      that promotes multimodal analgesia suggests that our findings are very likely to
      also be observed in non-ERAS settings and offers an opportunity to modify opioid
      prescribing practices on discharge after surgery. For opioid-free anesthesia and
      multimodal analgesia to influence the opioid epidemic, the dose and quantity of
      the opioids prescribed should be modified based on the information gathered by in
      hospital pain scores and opioid use as well as pain history before admission.

PMID- 29049124
TI  - Surgery-Induced Opioid Dependence: Adding Fuel to the Fire?

PMID- 29049125
TI  - Correlation between the pain numeric rating scale and the 12-item WHO Disability
      Assessment Schedule 2.0 in patients with musculoskeletal pain.
AB  - OBJECTIVE: The aim of this study was to assess the correlation between pain
      severity measured on a numeric rating scale and restrictions of functioning
      measured with the WHO Disability Assessment Schedule (WHODAS 2.0). PATIENTS AND
      METHODS: This was a cross-sectional study of 1207 patients with musculoskeletal
      pain conditions. Correlation was assessed using Spearman's and Pearson tests.
      RESULTS: Although all the Spearman's rank correlations between WHODAS 2.0 items
      and pain severity were statistically significant, they were mostly weak, with
      only a few moderate associations for 'S2 household responsibilities', 'S8
      washing', 'S9 dressing', and 'S12 day-to-day work'. The correlation between the
      WHODAS 2.0 total score and pain severity was also moderate: 0.41 [95% confidence
      interval (CI): 0.36-0.45] for average pain and 0.42 (95% CI: 0.37-0.46) for worst
      pain. The correlation between the WHODAS 2.0 total score and pain level was also
      assessed using Pearson's product-moment correlation, yielding figures that were
      similar to Spearman's correlation: 0.42 (P<0.0001, 95% CI: 0.37-0.46) for average
      pain and 0.39 (P<0.0001, 95% CI: 0.34-0.44) for worst pain. CONCLUSION: Among
      patients with chronic musculoskeletal pain, the correlation between pain severity
      measured by numeric rating scale and functioning level measured by WHODAS 2.0 was
      weak to moderate, with slightly stronger associations in physical domains of
      functioning.

PMID- 29049126
TI  - Shear-wave elastography for the assessment of liver fibrosis in liver transplant
      recipients treated for hepatitis C virus recurrence.
AB  - OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C
      therapy, and are also found to be effective in the liver transplant setting. The
      extent of liver fibrosis influences patient management and is used to monitor
      therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging
      based method that has not yet been studied extensively in liver transplant
      patients. Our aim was to study the effect of direct-acting antivirals in
      heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND
      METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were
      enrolled in this prospective study. The patients underwent 24 weeks of
      ombitasvir/paritaprevir/ritonavir+dasabuvir+/-ribavirin combination therapy.
      Elastographic examinations, serological tests and laboratory tests were
      performed, and serum biomarkers of liver fibrosis were calculated the day before
      treatment (baseline) and at the end of the treatment. RESULTS: All our patients
      became hepatitis C virus RNA negative by the end of the treatment. Median liver
      stiffness values decreased significantly after treatment compared with baseline
      (8.72+/-3.77 vs. 7.19+/-2.4 kPa; P<0.001). Among the studied laboratory values, a
      significant decrease was observed in the levels of alanine aminotransferase,
      aspartate aminotransferase and gamma-glutamyltransferase, whereas international
      normalized ratio levels increased. Serum biomarkers, namely aspartate
      aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly
      after treatment compared with baseline. CONCLUSION: In the present study, SWE was
      succesfully used to monitor the beneficial therapeutic effects of direct-acting
      antivirals in hepatitis C recurrence following liver transplantation. We believe
      that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C
      treatment in liver transplant patients.

PMID- 29049127
TI  - Hepatitis C virus infection and risk of Parkinson's disease: a systematic review
      and meta-analysis.
AB  - BACKGROUND/OBJECTIVE: Hepatitis C virus (HCV) infection is one of the most common
      infections worldwide. Recent epidemiologic studies have suggested that patients
      with HCV infection might be at an increased risk of Parkinson's disease. However,
      the data on this relationship remain inconclusive. This meta-analysis was
      conducted with the aim to summarize all available evidence. PATIENTS AND METHODS:
      A literature search was performed using MEDLINE and EMBASE database from
      inception to May 2017. Studies that reported relative risks, odd ratios (ORs), or
      hazard ratios comparing the risk of Parkinson's disease among HCV-infected
      patients versus participants without HCV infection were included. Pooled OR and
      95% confidence interval were calculated using a random-effect, generic inverse
      variance method. RESULTS: Of 468 studies, five studies with 323 974 participants
      met our eligibility criteria and were included in the analysis. We found a higher
      risk of Parkinson's disease among patients with chronic HCV infection compared
      with participants without HCV infection with the pooled OR of 1.35 (95%
      confidence interval: 1.19-1.52). The statistical heterogeneity of this study was
      insignificant (I=3%). The main limitation of this meta-analysis was the limited
      accuracy of diagnosis in the primary studies as they were coding-based studies.
      CONCLUSION: This study demonstrated a higher risk of Parkinson's disease among
      HCV-infected patients. Further studies are required to clarify how this risk
      should be addressed in the clinical picture.

PMID- 29049128
TI  - Changing pathological diagnosis from hyperplastic polyp to sessile serrated
      adenoma: systematic review and meta-analysis.
AB  - The WHO published a new classification of colonic polyps in 2010, including the
      group of serrated polyps, which can be divided into hyperplastic polyps (HP),
      traditional serrated adenomas, and sessile serrated adenomas (SSA) or polyps. To
      assess the rate of re-diagnosis of HP to SSA and to look for possible predictors
      for changing the diagnosis. English Medical literature searches were performed
      for 'reassessment' OR 'reclassification' AND 'hyperplastic polyp' OR 'sessile
      serrated adenoma' till 31 January 2017. PRISMA guidelines for systematic reviews
      were followed. Studies that included a precise re-diagnosis of HP into SSA were
      included. We also looked for predictors of SSA diagnosis such as polyp location
      and size, patient sex and age, and synchronous advanced adenoma. Altogether, we
      found 220 eligible studies; 212 were excluded as they did not fulfill the
      inclusion criteria and we were left with eight studies including 2625 patients.
      The odds ratio for the number of polyps with changed pathological diagnosis from
      HP to SSA was 0.112 with 95% confidence interval (CI): 0.099-0.126 (P<0.0001) or
      11.2%. Heterogeneity between studies was significant with Q=199.4, d.f. (Q)=9,
      P<0.0001, and I=95.486%. The odds ratio for changing the pathological diagnosis
      from HP to SSA for polyp proximal location and polyp size more than 5 mm were
      4.401, 95% CI: 2.784-6.958, P<0.0001, and 8.336, 95% CI: 4.963-15.571, P<0.0001,
      respectively. Endoscopists and pathologists should be aware of the SSA diagnosis
      when finding HPs larger than 5 mm in the right colon. The diagnosis of HP in
      these cases should be reassessed by experienced gastrointestinal pathologists.

PMID- 29049129
TI  - Transjugular intrahepatic portosystemic shunt placement before abdominal
      intervention in cirrhotic patients with portal hypertension: lessons from a pilot
      study.
AB  - BACKGROUND: Abdominal interventions are usually contraindicated in patients with
      cirrhosis and portal hypertension because of increased morbidity and mortality.
      Decreasing portal pressure with transjugular intrahepatic portosystemic shunt
      (TIPS) may improve patient outcomes. We report our experience with patients
      treated by neoadjuvant TIPS to identify those who would most benefit from this
      two-step procedure. PATIENTS AND METHODS: All patients treated by dedicated
      neoadjuvant TIPS between 2005 and March 2013 in two tertiary referral hospitals
      were included. The primary endpoint was the rate of failure, defined by the
      inability to proceed to the planned intervention after TIPS placement or
      persistent liver decompensation 3 months after intervention. The secondary
      endpoints were the rate of complications, parameters associated with failure, and
      1-year survival. RESULTS: Twenty-eight consecutive patients were included, with a
      mean age of 61.2+/-6.6 years, mean Child-Pugh score of 6.6+/-1.5, and mean model
      for end-stage liver disease score of 10.4+/-3.3. Procedures were digestive (43%)
      or liver (25%) resections, abdominal wall surgery (21%), or interventional
      gastrointestinal endoscopies (11%). The scheduled procedure was performed in 24
      (86%) patients within a median of 25 days after TIPS. Procedure failures occurred
      in six (21%) patients: four did not undergo surgery and two experienced
      persistent liver decompensation. Seven (25%) patients had postoperative
      complications, mainly local. Viral origin of cirrhosis, history of
      encephalopathy, and hepatic surgery were found to be associated with failure. One
      year survival in the whole cohort was 70%. CONCLUSION: In selected patients,
      extrahepatic surgery or interventional endoscopies can be safely performed after
      portal hypertension has been controlled by TIPS.

PMID- 29049130
TI  - Explanatory Versus Pragmatic Trials: An Essential Concept in Study Design and
      Interpretation.
AB  - Randomized clinical trials often represent the highest level of clinical evidence
      available to evaluate the efficacy of an intervention in clinical medicine.
      Although the process of randomization serves to maximize internal validity, the
      external validity, or generalizability, of such studies depends on several
      factors determined at the design phase of the trial including eligibility
      criteria, study setting, and outcomes of interest. In general, explanatory trials
      are optimized to demonstrate the efficacy of an intervention in a highly selected
      patient group; however, findings from these studies may not be generalizable to
      the larger clinical problem. In contrast, pragmatic trials attempt to understand
      the real-world benefit of an intervention by incorporating design elements that
      allow for greater generalizability and clinical applicability of study results.
      In this article we describe the explanatory-pragmatic continuum for clinical
      trials in greater detail. Further, a well-accepted tool for grading trials on
      this continuum is described, and applied, to 2 recently published trials
      pertaining to the surgical management of lumbar degenerative spondylolisthesis.

PMID- 29049131
TI  - Comparison of Surgical Outcomes, Narcotics Utilization, and Costs After an
      Anterior Cervical Discectomy and Fusion: Stand-alone Cage Versus Anterior
      Plating.
AB  - STUDY DESIGN: Retrospective cohort analysis of a prospectively maintained
      registry. OBJECTIVE: To compare the surgical outcomes, narcotic utilization, and
      costs between a stand-alone (SA) cage and anterior plating (AP) with an interbody
      device for 1-level anterior cervical discectomy and fusion (ACDF). BACKGROUND
      DATA: ACDF with a SA cage has gained popularity as a potential alternative to
      anterior cervical plating. Few studies have compared the surgical outcomes,
      narcotic utilization, and costs of ACDF utilizing a SA cage versus AP with an
      interbody device. METHODS: Patients who underwent a primary 1-level ACDF for
      degenerative spinal pathology between 2010 and 2013 were analyzed. Patients were
      stratified on the basis of the type of implant system (SA cage vs. AP) and
      assessed with regard to demographics, comorbidities, smoking, visual analogue
      scale (VAS) scores (preoperative/postoperative), procedural time, estimated blood
      loss (EBL), length of hospitalization, complications, reoperations, narcotic
      consumption, and total costs. Statistical analysis was performed with independent
      sample T tests for continuous variables and chi analysis for categorical data. An
      alpha level of <0.05 denoted statistical significance. RESULTS: Of the 93
      patients included, 52 (55.9%) underwent an ACDF with a SA cage system. Patient
      demographics, comorbidity burden, body mass index, smoking status, and
      preoperative VAS score were similar between cohorts. The SA cohort incurred a
      significantly lower EBL (P<0.001) than the AP cohort. However, none required a
      transfusion and the procedural time, length of hospitalization, postoperative VAS
      score, complication rates, 1-year arthrodesis rate, and reoperation rates were
      similar between cohorts. Postoperative narcotics consumption and total costs were
      also similar between groups. CONCLUSIONS: Our findings suggest that the SA cage
      may be associated with a significantly lower EBL, which may not be clinically
      relevant. Perioperative outcomes, complications, reoperation rates, narcotics
      consumption in the immediate postoperative period, and total costs may be similar
      regardless of the instrumentation utilized in a 1-level ACDF.

PMID- 29049132
TI  - One-Year Survival After In-Hospital Cardiac Arrest- does Pre-Arrest Sepsis
      Matter?
AB  - AIM: Cardiac arrest is not a common complication of sepsis, although sepsis has
      been recognized as one condition behind cardiac arrest. Our aim was to evaluate
      the prevalence of sepsis among patients with in-hospital cardiac arrest (IHCA),
      and to determine if sepsis is associated with inferior outcome after IHCA.
      METHODS: All consecutive emergency team dispatches in Turku University Hospital
      in 2011-2014 (n = 607) were reviewed retrospectively to identify the patients
      undergoing cardiopulmonary resuscitation (CPR) for IHCA (n = 301). The patient
      records were reviewed for the criteria of severe sepsis, organ dysfunction and
      chronic comorbidities before IHCA. Outcome was followed for one year. RESULTS:
      The criteria for pre-arrest severe sepsis were met by 83/301 (28%) of the
      patients, and 93/301 (31%) had multi-organ dysfunction (3 or more organ systems).
      The patients with severe sepsis had higher mortality than those without severe
      sepsis, increasing from 30-day-mortalities of 63/83 (76%) and 151/218 (69%),
      respectively (p = 0.256), to one-year-mortalities of 72/83 (87%) and 164/218
      (75%), respectively (p = 0.030). Emergency admission, age, immunosuppression, DM,
      multi-organ dysfunction and a non-shockable rhythm were independent predictors of
      one-year-mortality by multivariate logistic regression analysis. Six out of 83
      patients with severe sepsis before IHCA (7%) survived one year with good
      neurological outcome (CPC scale 1). CONCLUSION: A high proportion of patients
      with IHCA have sepsis and multi-organ dysfunction, and their prognosis is worse
      than the prognosis of patients with IHCA in general.

PMID- 29049133
TI  - HDL Cholesterol Efflux is Impaired in Older Patients with Early Sepsis: A
      Subanalysis of a Prospective Pilot Study.
AB  - BACKGROUND: Proper functioning of high-density lipoprotein (HDL) is necessary for
      protection against sepsis. However, previous work has demonstrated that HDL
      becomes oxidized and dysfunctional (Dys-HDL) during sepsis. Older (aged >65
      years) patients are at particularly high risk of sepsis and poor outcomes from
      sepsis. STUDY OBJECTIVE: The aim of the study was to compare functional
      properties of HDL (cholesterol efflux capacity and paraoxonase enzyme 1 [PON-1]
      activity) and Dys-HDL between older (aged >65 years) sepsis patients and older
      healthy volunteers. METHODS: This was a subanalysis of a prospective study in
      which patients with sepsis were prospectively enrolled from the emergency
      department within the first 24 h. Serum and plasma samples were drawn from septic
      patients and age- and sex-matched control subjects. Percent cholesterol efflux,
      HDL inflammatory index, and PON1 activity were measured. Data were analyzed using
      Student t test or Wilcoxon rank-sum test. RESULTS: Ten sepsis and 10 healthy
      controls were analyzed. Mean age of sepsis patients (80 +/- 2 years [SD]) and
      control subjects (77 +/- 2 years) was similar (P = 0.31). Mean systolic blood
      pressures were significantly different in sepsis patients (113 +/- 8 mmHg)
      compared with controls (133 +/- 6 mmHg) (P = 0.049). Median SOFA scores for
      sepsis patients were 5.5 (interquartile range [IQR] 4-9). Mean percent
      cholesterol efflux was significantly reduced in sepsis (24.1 +/- 1.2%) compared
      with controls (31.5 +/- 1.0%) (P < 0.001). HDL inflammatory index was also
      significantly elevated in septic patients (1.63, IQR 1.3-2.34) compared with
      controls (0.62, IQR 0.56-0.67) (P < 0.001). However, PON1 activity was not
      significantly different between septic patients (70.3 +/- 16.3 nmol/min/mL) and
      control subjects (88.8 +/- 18.3 nmol/min/mL). CONCLUSIONS: Cholesterol efflux
      capacity seems to be significantly impaired in sepsis patients who also exhibited
      a higher index of Dys-HDL. The findings suggest that HDL function may be impaired
      in older individuals with sepsis.

PMID- 29049134
TI  - In Trauma Patients, the Occurrence of Early-Onset Nosocomial Infections is
      Associated With Increased Plasma Concentrations of Chromogranin A.
AB  - In previously healthy persons suffering from acute illnesses, nosocomial
      infections (NIs) are frequent. Their prevalence suggests the existence of as yet
      unknown conditions that may promote care-related infection. This study assessed
      whether the measurement of plasma chromogranin A, a stress-related protein
      involved in innate defense, is related to NI risk, and whether any chromogranin A
      derived fragment included in vasostatin-I displays immunosuppressive activities
      related to AP-1 or NF-kappa B downregulation. At the clinical level, trauma
      patients and healthy controls were recruited to be eligible. Clinical histories
      were recorded, and standard biological tests (including plasma chromogranin A)
      were performed. For 9 randomly chosen patients and 16 controls, the time
      dependent concentrations of chromogranin A (CGA) were assessed twice a day over
      66 h. The data show that trauma patients present a higher value of CGA
      concentration during 66 h in comparison with healthy controls. In addition,
      patients maintaining this significant increase in CGA readily develop NIs. We
      therefore studied the effects of chromogranin A-derived peptides on monocytes,
      focusing on transcription factors that play a central role in inflammation. In
      vitro assay demonstrated that a chromogranin A-derived fragment (CGA47-70)
      displays a significant inhibition of NF-kappa B and AP-1 transcriptional
      activities in these cells. In conclusion, the occurrence of NI in trauma patients
      is associated with significantly increased plasma CGA concentrations.
      Downregulation of the two transcription factors by CGA47-70 might induce early
      acquired immune defect after a serious medical stress.

PMID- 29049135
TI  - Early Identification of the Patient with Endotheliopathy of Trauma by Arrival
      Serum Albumin.
AB  - OBJECTIVE: Traumatic endotheliopathy (EoT) is associated with glycocalyx
      breakdown and capillary leak resulting in the extravasation of proteins. We
      hypothesized that lower serum albumin levels are associated with EoT, poor
      outcomes, and can be used for early EoT screening in trauma patients. METHODS: We
      enrolled severely injured trauma patients with serum albumin levels available on
      admission. Syndecan-1 and soluble thrombomodulin were quantified from plasma by
      ELISA. Demographic and clinical data were obtained. We evaluated the association
      of serum albumin and EoT+ (syndecan-1 level >=40 ng/mL), followed by
      dichotomization by serum albumin level, and subgroup comparisons. RESULTS: Of the
      258 patients enrolled 92 (36.0%) were EoT+ (syndecan-1 >= 40 ng/mL). Median
      albumin levels in the EoT+ group were 3.4 g/dL, and 3.8 g/dL in EoT- patients, P
      < 0.05. In a multifactorial analysis, lower albumin levels were inversely
      associated with the likelihood of EoT+. With receiver characteristic curve
      analysis, we determined a cutoff albumin level < 3.6 g/dL for EoT+ prediction
      (area under the curve 0.70; 95% CI: 0.63, 0.77). After dichotomizing by albumin
      <3.6 or >=3.6 g/dL, 51.5% of patients had low albumin. Low albumin patients were
      more likely to have EoT+, as well as higher soluble thrombomodulin (both P <
      0.05). Furthermore, they required more frequently blood transfusions, had fewer
      hospital-free days and higher mortality rate than those with normal albumin.
      CONCLUSIONS: EoT is a syndrome associated with leakage of albumin from the
      intravascular compartment, which re-emphasizes that arrival albumin may be a
      novel and timely approach to the identification of patients needing endothelial
      rescue therapy.

PMID- 29049136
TI  - Comparisons of Traditional Metabolic Markers and Compensatory Reserve as Early
      Predictors of Tolerance to Central Hypovolemia in Humans.
AB  - Circulatory shock remains a leading cause of death in both military and civilian
      trauma. Early, accurate and reliable prediction of decompensation is necessary
      for the most efficient interventions and clinical outcomes. Individual tolerance
      to reduced central blood volume can serve as a model to assess the sensitivity
      and specificity of vital sign measurements. The compensatory reserve (CRM) is the
      measurement of this capacity. Measurements of muscle oxygen saturation (SmO2),
      blood lactate, and end tidal CO2 (EtCO2) have recently gained attention as
      prognostic tools for early assessment of the status of patients with progressive
      hemorrhage, but lack the ability to adequately differentiate individual tolerance
      to hypovolemia. We hypothesized that the CRM would better predict hemodynamic
      decompensation and provide greater specificity and sensitivity than metabolic
      measures. To test this hypothesis, we employed lower body negative pressure on
      healthy human subjects until symptoms of presyncope were evident. Receiver
      operating characteristic area under the curve (ROC AUC), sensitivity, and
      specificity were used to evaluate the ability of CRM, partial pressure of oxygen
      (pO2), partial pressure of carbon dioxide (pCO2), SmO2, lactate, EtCO2, potential
      of hydrogen (pH), base excess and hematocrit (Hct) to predict hemodynamic
      decompensation. The ROC AUC for CRM (0.94) had a superior ability to predict
      decompensation compared with pO2 (0.85), pCO2 (0.62), SmO2 (0.72), lactate
      (0.57), EtCO2 (0.74), pH (0.55), base excess (0.59), and Hct (0.67). Similarly,
      CRM also exhibited the greatest sensitivity and specificity. These findings
      support the notion that CRM provides superior detection of hemodynamic
      compensation compared with commonly used clinical metabolic measures.

PMID- 29049137
TI  - Effects of Dextran-70 and Albumin on Coagulation in Experimental Hemorrhage in
      the Guinea Pig.
AB  - BACKGROUND: Dextran-70 is a more potent plasma volume expander than albumin but
      use has been hampered because of its antithrombotic properties. However, also
      albumin has antithrombotic properties and little is known about relative effects
      of these two colloids on coagulation in vivo when controlling for differences in
      efficacy as plasma volume expanders. AIM: Compare effects of dextran-70 and
      albumin on coagulation at a dose resulting in equal plasma volume expansion.
      METHODS: Guinea pigs were subjected to a 25 mL/kg hemorrhage during 20 min and
      randomized to resuscitation with either 6% dextran-70 at a dose of 15 mL/kg or 5%
      albumin at a dose of 25 mL/kg (n = 14 in each group) during 30 min starting 1 h
      of shock. Blood samples were collected at the completion of resuscitation and at
      4 h. Plasma volume was measured using I-albumin and the effect on coagulation was
      evaluated using whole blood thrombelastography (TEG), measurement of plasma
      fibrinogen and von Willebrand factor (vWF) concentrations and vWF glycoprotein 1b
      (GP1b) A activity. RESULTS: Plasma volumes after resuscitation were similar in
      the groups at both time points. Dextran-70 resulted in a transient prolongation
      of TEG clot amplification time (K) at the completion of resuscitation compared
      with albumin. TEG clot initiation (R) and strength (MA) did not differ between
      the treatments at any of the time points. Albumin reduced vWF concentrations to a
      larger extent than dextran at both time points, whereas no difference in vWF
      GP1bA activity or in plasma fibrinogen and could be detected. CONCLUSION: In
      equipotent doses with regard to plasma volume expansion, dextran-70 transiently
      prolongs clot amplification time more than albumin whereas dextran-70 reduces
      plasma vWF concentrations less than albumin.

PMID- 29049138
TI  - Graph Theoretical Analysis of Genome-Scale Data: Examination of Gene Activation
      Occurring in the Setting of Community-Acquired Pneumonia.
AB  - INTRODUCTION: We have previously reported evidence that Black individuals appear
      to have a significantly higher incidence of infection-related hospitalizations
      compared with White individuals. It is possible that the host immune response is
      responsible for this vital difference. In support of such a hypothesis, the aim
      of this study was to determine whether Black and White individuals exhibit
      differential whole blood gene network activation. METHODS: We examined whole
      blood network activation in a subset of patients (n = 22 pairs, propensity score
      matched (1:1) Black and White patients) with community-acquired pneumonia (CAP)
      from the Genetic and Inflammatory Markers of Sepsis study. We employed day one
      whole blood transcriptomic data generated from this cohort and constructed co
      expression graphs for each racial group. Pearson correlation coefficients were
      used to weight edges. Spectral thresholding was applied to ascribe significance.
      Innovative graph theoretical methods were then invoked to detect densely
      connected gene networks and provide differential structural analysis. RESULTS:
      Propensity matching was employed to reduce potential bias due to confounding
      variables. Although Black and White patients had similar socio- and clinical
      demographics, we identified novel differences in molecular network activation
      dense subgraphs known as paracliques that displayed complete gene connection for
      both White (three paracliques) and Black patients (one paraclique). Specifically,
      the genes that comprised the paracliques in the White patients include circadian
      loop, cell adhesion, mobility, proliferation, tumor suppression, NFkappaB, and
      chemokine signaling. However, the genes that comprised the paracliques in the
      Black patients include DNA and messenger RNA processes, and apoptosis signaling.
      We investigated the distribution of Black paracliques across White paracliques.
      Black patients had five paracliques (with almost complete connection) comprised
      of genes that are critical for host immune response widely distributed across 22
      parcliques in the White population. Anchoring the analysis on two critical
      inflammatory mediators, interleukin (IL)-6 and IL-10 identified further
      differential network activation among the White and Black patient populations.
      CONCLUSIONS: These results demonstrate that, at the molecular level, Black and
      White individuals may experience different activation patterns with CAP. Further
      validation of the gene networks we have identified may help pinpoint genetic
      factors that increase host susceptibility to community-acquired pneumonia, and
      may lay the groundwork for personalized management of CAP.

PMID- 29049139
TI  - The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal
      behavior: systematic review and meta-analysis.
AB  - The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to
      influence suicidal behavior. The aim of our study was to explore the role of the
      HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior
      through a systematic review and meta-analysis. The search was performed using
      EBSCO and PubMed databases. To be included in the analysis, the studies had to
      evaluate suicidal behavior (attempted, ideation, or completed suicide). The
      results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C
      lies on chromosome X, pooled ORs were calculated, respectively, for each of the
      models used, namely: allelic, homozygous, dominant, and recessive for the female
      group and allelic for the male group. The meta-analysis comprised 3867
      individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318)
      polymorphism did not show a significant association with suicidal behavior either
      in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95%
      confidence interval: 0.64-1.23). Similarly, nonsignificant associations were
      observed for all of the genetic models used in any of the populations/subgroups
      studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not
      associated with suicidal behavior. However, because of the study limitations, we
      suggest more researches should be performed, increasing the sample sizes and
      statistical power, to determine the association between the rs6318 variant and
      suicidal behavior.

PMID- 29049140
TI  - Metopism: a Study of the Persistent Metopic Suture.
AB  - Metopism, the persistence of the metopic suture in adulthood, is a clinically
      significant radiographic finding. In addition to masquerading as a fracture of
      the frontal bone, a persistent metopic suture may be associated with other
      clinically significant anatomical variations including frontal sinus
      abnormalities. Several geographically and craniofacially distinct populations
      have yet to be assessed for the prevalence of metopism. This study aimed to
      determine the prevalence of metopic sutures in adult crania of diverse
      populations among which scant research exists. A total of 505 adult crania were
      examined for the presence of a metopic suture. A total of 13 (2.57%) demonstrated
      metopism. Among subpopulations, metopism was present in 8.06% (5:62) of European
      crania, 15.38% (2:13) of East Asian crania, 2.20% (2:91) of Egyptian crania, and
      2.86% (1:35) of Bengali crania. Metopism was also found in 1 Chilean, Roman, and
      Tchuktchi cranium, respectively. Metopism was not seen in crania from individuals
      of African (non-Egyptian) descent (0:62), Peruvians (0:144), Malayans (0:23), or
      Mexicans (0:23). Among sexes, metopism was present in 3.77% (8:212) of females
      and 1.79% (5:279) of males. The prevalence of metopism differs between
      populations and sexes. The results of this study provide anthropological,
      developmental, and clinical insight with regard to metopism.

PMID- 29049142
TI  - 13-93B3 Bioactive Glass: a New Scaffold for Transplantation of Stem Cell-Derived
      Chondrocytes.
AB  - Research using animal models gives human trials hope for recovery in many fields
      of regenerative medicine, although they are sometimes poor predictors for human
      experiences. Our goal was to investigate whether rat chondrocytes, differentiated
      from adipose-derived stem cells, could be transplanted using a new, easily
      shaped, bioactive glass scaffold, and to show the immunohistochemical results.
      Intraperitoneal and retroperitoneal adipose tissue was extracted from 6 male
      Wistar albino type rats. The fatty tissue samples were fragmented and incubated.
      Chondrogenic differentiation was carried out and collagen type II, bFGF, and Sox
      9 immunohistochemical characterization analysis was performed. Differentiated
      chondrocytes were implanted on 13-93B3 bioactive glass scaffolds and transplanted
      into the right ears of the rats. As control, only the biomaterial was
      transplanted into the left ears of the rats. After 1 month, the rats were
      sacrificed and transplantation areas were examined immunohistochemically.
      Histological examination of control samples from the left ears revealed that the
      biomaterial was covered with connective tissue, its general structure was
      preserved, and resorption of the scaffold had started. In specimens from the
      right ears, the biomaterial was covered with connective tissue, its structure was
      preserved, cartilage cells were present around the biomaterial, and the presence
      of cartilage tissue was demonstrated immunohistochemically. In conclusion, 13
      93B3 bioactive glass scaffold contributed to the formation of new collagen and
      the survival of chondrocytes, and is a promising new biomaterial that will prove
      very useful in regenerative medicine.

PMID- 29049143
TI  - Hemodynamic Changes in Paramedian Forehead Flap.
AB  - Paramedian forehead flap is a workhorse for nasal reconstruction. However,
      vascular complications may lead to flap failure. The purpose of this study was to
      evaluate the blood flow objectively and determine the hemodynamic changes in
      paramedian forehead flap with respect to influential factors of age, gender, and
      smoking. Thirty patients who had paramedian forehead flap were followed up
      prospectively between 2010 and 2013. The blood flow was assessed by resistance
      index using Color Duplex-Doppler Ultrasonography. Resistance index was measured
      at the proximal and distal ends of each flap on the postoperative first day,
      first week, and second week. All data were analyzed using SPSS 15.0 for Windows.
      Fifteen patients were female and the mean of age was 60.9 years. Our results
      demonstrated statistically significant differences with gradual decreases in
      resistance to blood flow, when the resistance index values at the proximal and
      distal ends of paramedian forehead flap were compared (P < 0.001 and P < 0.001).
      Age, gender, and smoking did not have a negative impact on the resistance index
      values of paramedian forehead flap. To the best of our knowledge, this is the
      first study in which resistance in blood flow and hemodynamic changes of
      paramedian forehead flap were objectively determined using Color Duplex-Doppler
      Ultrasonography. The resistance index gradually decreases, although it is
      considerably high at the early postoperative interval. Age, gender, and smoking
      do not adversely influence the blood flow in a well-designed paramedian forehead
      flap.

PMID- 29049144
TI  - The Etiology of Neuronal Development in Craniosynostosis: A Working Hypothesis.
AB  - Craniosynostosis is one of the most common craniofacial conditions treated by
      neurologic and plastic surgeons. In addition to disfigurement, children with
      craniosynostosis experience significant cognitive dysfunction later in life.
      Surgery is performed in infancy to correct skull deformity; however, the field is
      at a crossroads regarding the best approach for correction. Since the cause of
      brain dysfunction in these patients has remained uncertain, the role and type of
      surgery might have in attenuating the later-observed cognitive deficits through
      impact on the brain has been unclear. Recently, however, advances in imaging such
      as event-related potentials, diffusion tensor imaging, and functional MRI, in
      conjunction with more robust clinical studies, are providing important insight
      into the potential etiologies of brain dysfunction in syndromic and nonsyndromic
      craniosynostosis patients. This review aims to outline the cause(s) of such brain
      dysfunction including the role extrinsic vault constriction might have on brain
      development and the current evidence for an intrinsic modular developmental error
      in brain development. Illuminating the cause of brain dysfunction will identify
      the role of surgery can play in improving observed functional deficits and thus
      direct optimal primary and adjuvant treatment.

PMID- 29049145
TI  - Hydatid Cyst of the Parotid Gland: A Rare Location.
AB  - Hydatid disease of the parotid gland is a very rare entity and may be easily
      overlooked in the diagnosis of parotid masses. Although Turkey remains an endemic
      area for echinococcosis, involvement of the parotid gland is extremely rare. A 26
      year-old man presented with primary parotid gland mass without any other organ
      involvement. During the first surgery, the cyst was perforated accidentally and
      in a short time recurrence was occurred. Maximum attention was given for the
      second surgery for total removal without damaging the cyst with medical
      treatment. The clinicians should take hydatid disease of parotid gland into
      consideration and great care must be given for not damaging the capsule of the
      cystic tumors in order to prevent recurrences.

PMID- 29049146
TI  - Outcomes of Titanium Mesh Cranioplasty in Pediatric Patients.
AB  - PURPOSE: Cranial defects in children have been repaired with various materials
      ranging from autologous bone to synthetic materials. There is little published
      literature on the outcomes of titanium mesh cranioplasty (TMC) in calvarial
      reconstruction in the pediatric population. This study evaluates a pediatric
      cohort who underwent calvarial defect reconstruction with titanium mesh and
      assesses the efficacy and outcomes of TMC. METHODS: An Institutional Review Board
      approved retrospective review of patients <=18 years of age who underwent
      cranioplasty from 1999 to 2014 at 2 centers was performed. The cohort undergoing
      TMC was studied. RESULTS: A total of 159 cranioplasties were performed.
      Autologous reconstruction included 84 bone flap replacements and 36 split
      calvarial bone graft reconstructions. Six patients underwent PEEK implant
      reconstruction. Titanium mesh cranioplasty was performed on 33 patients. Two
      patients underwent 2 separate cranioplasties. The median age of patients was 6
      years (19 months to 18 years). The most common underlying etiologies were
      congenital syndromes/craniosynostosis (13 patients), and trauma (11). The
      majority of patients had prior cranial surgeries (85%). Various types of titanium
      mesh were used with sizes ranging from 2*3 cm to 19*20 cm, with some patients
      requiring distinct areas of defect reconstruction. Perioperative complications
      were noted in 2 patients that subsequently improved. Two patients had late soft
      tissue problems with complications of wound infections requiring resection of a
      portion of the mesh. Patients were followed an average of 4 years (range 13 days
      to 6.8 years), with 2 patients lost to follow-up. Overall, all patients with
      follow-up achieved a cranial contour with good symmetry to the unaffected side,
      as well as effective protection to the brain. CONCLUSIONS: Titanium mesh
      cranioplasty is an effective option for correcting pediatric cranial defects when
      autologous bone availability is limited and soft tissue coverage allows placement
      of an implant. The interim outcome for these patients is favorable with few
      complications and no evidence of growth restriction in the authors' series.
      Follow-up will be ongoing for these patients.

PMID- 29049147
TI  - Virtual Reality Model of the Three-Dimensional Anatomy of the Cavernous Sinus
      Based on a Cadaveric Image and Dissection.
AB  - OBJECTIVE: Studying the three-dimensional (3D) anatomy of the cavernous sinus is
      essential for treating lesions in this region with skull base surgeries. Cadaver
      dissection is a conventional method that has insurmountable flaws with regard to
      understanding spatial anatomy. The authors' research aimed to build an image
      model of the cavernous sinus region in a virtual reality system to precisely,
      individually and objectively elucidate the complete and local stereo-anatomy.
      METHODS: Computed tomography and magnetic resonance imaging scans were performed
      on 5 adult cadaver heads. Latex mixed with contrast agent was injected into the
      arterial system and then into the venous system. Computed tomography scans were
      performed again following the 2 injections. Magnetic resonance imaging scans were
      performed again after the cranial nerves were exposed. Image data were input into
      a virtual reality system to establish a model of the cavernous sinus. Observation
      results of the image models were compared with those of the cadaver heads.
      RESULTS: Visualization of the cavernous sinus region models built using the
      virtual reality system was good for all the cadavers. High resolutions were
      achieved for the images of different tissues. The observed results were
      consistent with those of the cadaver head. The spatial architecture and modality
      of the cavernous sinus were clearly displayed in the 3D model by rotating the
      model and conveniently changing its transparency. CONCLUSION: A 3D virtual
      reality model of the cavernous sinus region is helpful for globally and
      objectively understanding anatomy. The observation procedure was accurate,
      convenient, noninvasive, and time and specimen saving.

PMID- 29049148
TI  - Skull Base Neuroendoscopic Training Model Using a Fibrous Injectable Tumor
      Polymer and the Nico Myriad.
AB  - The Myriad is an innovative, high precision tool for tumor resection, designed to
      work within narrow endoscopic corridors. Due to its application in technically
      demanding situations, the learning curve associated with its use might be
      extremely challenging and time-consuming.The authors describe the application of
      an already validated training model, the skull base injectable tumor model (ITM),
      to allow trainees to practice with the use of the Myriad during endoscopic skull
      base procedures.A formalin embalmed cadaveric head was used for technical
      assessment. Stratathane resin ST-504 derived polymer was injected to mimic skull
      base tumors and Myriad was used for tumor resection during different endoscopic
      procedures.An endoscopic endonasal transsphenoidal, a trans-planum trans
      tuberculum, and a trans-clival approach have been performed after ITM injection.
      The Myriad was used for tumor debulking and blunt manipulation, qualitatively
      evaluating the technical challenges in performing the surgical
      dissection.Injectable tumor model demonstrates to be a valuable educational tool
      to train surgeons in the use of Myriad, potentially speeding up the learning
      curve in the acquirement of necessary technical skills in manipulating the
      instrument, even in case of demanding surgical situation.

PMID- 29049150
TI  - A Sigh Too Deep for Words.

PMID- 29049149
TI  - A Modification to the Nasal Septal Chain Suture Which Improves Its Application.
AB  - INTRODUCTION: A novel modification to the nasal septal chain suture which makes
      its application easier and faster without using any special surgical instrument
      has been described in this study. The advantage of the modification was evaluated
      in terms of the suture application time. METHODS: A total of 40 patients with a
      mean age of 30.1 +/- 10.6 (18-58) years were evaluated in 2 groups. A nasal
      septal chain suture was applied with the previously described technique and the
      new modification for each group after the patients underwent septoplasty. The
      suture application time for all of the patients was recorded. RESULTS: The mean
      suture application time was 455.2 +/- 36.5 (380-530) seconds in the previous
      technique group and 404.7 +/- 29.4 (340-450) seconds in the modified technique
      group. The use of new modification of the technique was found to shorten the
      suture application time significantly (P < 0.001). CONCLUSION: The modified nasal
      septal chain suture that has been described in this study can be an option to
      nasal septal suturation since it can be used with absorbable or nonabsorbable
      materials, is easy to remove, and does not cause pain during suture removal.

PMID- 29049151
TI  - November Is National Family Caregiver's Month: How Nurse Educators Can Help.

PMID- 29049152
TI  - Essential Professional Behaviors of Nursing Students and New Nurses: Hospital
      Nurse Leader Perspectives Survey.
AB  - AIM: This two-part study was conducted to determine which professional behaviors
      hospital nurse leaders believe are essential for nursing students to learn in the
      classroom. BACKGROUND: Nursing students need to be educated to lead high-quality
      care in complex health care environments. Little is known regarding the
      professional behaviors deemed essential for novice nurses. METHOD: Hospital
      leaders were surveyed (n = 221) using the Hospital Nurse Leader Perspectives
      survey. This survey, developed from interviews, includes 41 items in change,
      communication, conflict, leadership, and self-awareness. RESULTS: The highest
      ranked category was communication (n = 159, 72 percent), followed by self
      awareness (n = 32, 14.4 percent). The highest items in each category were patient
      communication, prioritization, expect change, learning from failure, and conflict
      resolution. CONCLUSION: The results provide practical information to inform
      curricula and prepare leaders.

PMID- 29049153
TI  - PhD Education Outcomes: Results of a National Survey of Nursing PhD Alumni.
AB  - AIM: A national survey was conducted to examine the relationship between
      individual students' experiences and nursing PhD program characteristics and
      program outcomes. BACKGROUND: In light of the shortage of doctorally prepared
      nurse scientists and a growth in nursing PhD programs, an examination of the PhD
      nursing education experience in relation to educational outcomes is timely.
      METHOD: Data were collected from graduates of a 50 percent random sample of
      nursing PhD programs in the United States. RESULTS: Graduates who had worked as
      research assistants, attended classroom-based programs, and worked as a nurse no
      more than 12 hours per week during their PhD education were more likely to have
      successful publication records and receive external research grant funding than
      graduates who did not have these experiences. CONCLUSION: On the basis of
      traditionally accepted measures of research productivity, our results indicate
      that nursing PhD programs have limited success in producing nurse researchers.

PMID- 29049154
TI  - Self-Esteem, Locus of Control, and First-Time NCLEX-RN Passage of BSN Students at
      Historically Black Colleges and Universities.
AB  - AIM: Relationships between self-esteem, locus of control (LOC), and first-time
      passage of National Council Licensure Examination for Registered Nurses (NCLEX
      RN(r)) were examined at baccalaureate nursing programs at two historically black
      colleges and universities. BACKGROUND: Shortages continue to exceed demands for
      RNs prepared at the baccalaureate level. Inconsistent pass rates on the NCLEX-RN
      for graduates of historically black colleges and universities impede the supply
      of RNs. METHOD: Surveys and archival data were used to examine characteristics of
      the sample and explore relationships among variables. RESULTS: All participants
      (N = 90) reported high self-esteem and internal LOC. Models suggested that all
      those with high self-esteem and internal LOC would pass the NCLEX-RN; only 85
      percent passed the first time. CONCLUSION: Statistical analysis revealed a lack
      of statistical significance between self-esteem, LOC, and first-time passage.
      Variables not included in the study may have affected first-time passage.

PMID- 29049155
TI  - Quality Standards for Online Learning.

PMID- 29049156
TI  - NLN Releases A Vision for Graduate Preparation for Academic Nurse Educators.

PMID- 29049157
TI  - Moral Distress and Associated Factors among Baccalaureate Nursing Students: A
      Multi-Site Descriptive Study.

PMID- 29049158
TI  - Advanced Nursing Education: Critical Factors That Influence Diploma and Associate
      Degree Nurses to Advance.
AB  - AIM: The purpose of this study was to gain an understanding of the social
      processes associated with the decision of diploma and associate degree nurses to
      advance academically. BACKGROUND: Advanced nursing education needs to be pursued
      along the continuum of the nursing career path. This education process is
      indispensable to the role of nurses as educator, manager, nurse leader, and
      researcher who will effect policy changes, assume leadership roles as
      revolutionary thinkers, and implement paradigmatic shifts. METHOD: Data were
      collected from two groups of participants using face-to-face, semistructured
      interviews. Group 1 consisted of diploma and associate degree nurses; Group 2
      consisted of baccalaureate, masters, and doctoral degree nurses who have
      progressed academically. RESULTS: Emerging from the thick, rich data were core
      categories of rewarding, motivating, and supporting as critical factors that
      influence professional advancement. CONCLUSION: This qualitative study elucidated
      that professional advancement was the social process that grounds. The emergent
      theory was the theory of professional advancement.

PMID- 29049160
TI  - Kahoot! in the Classroom: Student Engagement Technique.

PMID- 29049161
TI  - Innovative Precepting Strategy.

PMID- 29049162
TI  - Liver Pursuit!

PMID- 29049163
TI  - Examining the association of MMP-1 gene -1607 (2G/1G) and -519 (A/G)
      polymorphisms with the risk of osteomyelitis: A case-control study.
AB  - To investigate the effects of matrix metalloproteinase-1 (MMP-1) gene
      polymorphisms on the onset of osteomyelitis in Chinese Han population.In all, 80
      osteomyelitis patients (case group) and 81 healthy people (control group) were
      recruited into this case-control study. Polymerase chain reaction-restriction
      fragment length polymorphism method was utilized to examine the genotypes of MMP
      1 polymorphisms (-1607 2G/1G and -519A/G) in the 2 groups. Genotype and allele
      differences between the case and control groups were analyzed by chi-square test.
      Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to
      present the association strength between MMP-1 gene polymorphisms and
      osteomyelitis.Frequencies of -1607 2G/2G genotype between the case and control
      groups were statistically significant (P = .025). Compared with 1G/1G genotype
      carriers, the 2G/2G genotype carriers had 1.605 times risk of developing
      osteomyelitis (OR 2.605, 95% CI 1.116-6.082). Meanwhile, the 2G allele
      significantly associated with the risk of osteomyelitis (OR 1.735, 95% CI 1.115
      2.701). In addition, frequency of -519GG genotype was obviously higher in case
      group than that in control group (P = .024), and GG genotype related to an
      increased risk of osteomyelitis (OR 2.792, 95% CI 1.127-6.917). Whereas, the 
      519G allele may be a susceptible factor for osteomyelitis (OR 1.622, 95% CI 1.038
      2.536).The MMP-1 -1607 (2G/1G) and -519 (A/G) polymorphisms may contribute to the
      onset of osteomyelitis.

PMID- 29049164
TI  - Electrocardiogram in patients with acute inferior myocardial infarction due to
      occlusion of circumflex artery.
AB  - To investigate the diagnostic value of electrocardiographic (ECG) ST-segment in
      acute inferior myocardial infarction (AIMI) caused by the left circumflex branch
      (LCX).A total of 240 clinical cases with AIMI in our hospital were
      retrospectively analyzed. All of them had received percutaneous coronary
      intervention (PCI) within 12 hours after symptom onset. The clinical features,
      ECG manifestations, and coronary artery lesion characteristics of the patients
      were collected.The right coronary artery (RCA) was shown to be the infarct
      related artery (IRA) in 177 patients, while LCX was responsible for AIMI in 63
      cases. There was no significant difference in the risk factors of coronary heart
      disease (CHD) (P > .05 for all) between the 2 groups. ST-segment elevation in
      lead II, III, and AVF could be found in all patients. Moreover, ST-segment
      depression in lead I (STD I), ST-segment elevation in lead III (STE III), STE III
      STE II, STE AVF, STD AVL, STD AVL-STD I and STE v6 lead ST-segment deviation
      exhibited significant difference in 2 groups (P < .05 for all). The changes of
      STD I, STE III < STEII, STD AVL < STD I could discriminate between LCX and RCA in
      AIMI patients with high sensitivity and specificity.ECG may be an effective tool
      to predict the IRA in patient with AIMI.

PMID- 29049165
TI  - Effects of different methods of general anesthesia on intraoperative awareness in
      surgical patients.
AB  - The purpose of the study was to investigate the effects of total intravenous
      anesthesia (TIVA) and combined of intravenous and inhaled anesthesia (CIIA) on
      intraoperative awareness in surgical patients.A total of 678 patients were
      recruited in the CIIA group, while TIVA group included 566 patients. The clinical
      characteristics and the occurrence of intraoperative awareness were compared
      between the groups. Mini-Mental State Examination, Generalized Anxiety Disorder
      7, and Patient Health Questionnaire 9 tests were performed to estimate cognitive
      and psychological functions of the patients. In addition, logistic regression
      analysis was applied to identify the risk factors for intraoperative awareness in
      surgical patients.In CIIA group, 3 patients (0.44%) were confirmed with
      intraoperative awareness, while 11 patients (1.94%) in TIVA group underwent
      intraoperative awareness. The occurrence rate of intraoperative awareness was
      significantly higher in VITA group than that in the CIIA group (P = .029).
      Awareness classification demonstrated that intraoperative awareness mainly
      included auditory, tactile, and pain perceptions. Moreover, 4 patients showed
      distress after operation. Patients with intraoperative awareness exhibited poor
      performance in cognitive and psychological tests (P < .001 for all). Logistic
      regression analysis demonstrated that CIIA (odds ratio [OR] = 0.198, 95%
      confidence interval [CI] = 0.047-0.827), age (OR = 0.951, 95% CI = 0.908-0.997),
      midazolam application (OR = 0.158, 95% CI = 0.034-0.736), awareness history (OR =
      10.131, 95% CI = 2.206-45.517), and duration of surgery (OR = 1.016, 95% CI =
      1.001-1.032) were significantly associated with intraoperative
      awareness.Intraoperative awareness can significantly influence the cognitive and
      psychological functions of surgical patients. CIIA and midazolam application may
      lower the risk of intraoperative awareness.

PMID- 29049166
TI  - Safety of potassium-bearing citrate in patients with renal transplantation: A
      case report.
AB  - RATIONALE: Urinary lithiasis is one of severe postoperative complications in
      patients undergoing renal transplantation, possibly leading to anuria, urinary
      infection, or even acute renal failure. Potassium sodium hydrogen citrate (PSHC),
      a potassium-bearing citrate, is commonly prescribed to prevent stone formation.
      PATIENT CONCERNS: A 25-year-old man (patient 1) and a 31-year-old man (patient 2)
      receiving renal transplantation for end-stage renal disease (ESRD) were enrolled
      in this study. They were given 10 g/day of PSHC granules from the ninth day to
      the 17th day after surgery. Patient 1 presented chest tightness, nausea, muscle
      weakness, and ascending paralysis on the 10th day. Patient 2 presented weak waves
      on EGG on the 17th day. Moreover, their serum potassium concentrations (SPCs)
      were 7.67 and 6.05 mmol/L, respectively. DIAGNOSIS: Acute hyperkalemia.
      INTERVENTIONS: Hemo-filtration was performed for patient 1, while patient 2
      received 10% calcium gluconate 10 mL, 5% NaHCO3 125 mL, and 10% glucose 500 mL
      with the addition of 10 units of insulin through intravenous drip. OUTCOMES:
      Their SPCs dropped to the normal range. LESSONS: Physicians should pay close
      attentions to potential risks caused by PSHC, and monitor the SPCs to minimize
      the occurrence of hyperkalemia.

PMID- 29049167
TI  - Decreased expression of RASSF10 correlates with poor prognosis in patients with
      colorectal cancer.
AB  - Ras association domain protein 10 (RASSF10) was reported to act as a prognostic
      indicator in various types of cancer and it was proved to be tumor suppressor
      gene in colorectal cancer (CRC). The purpose of this study was to evaluate the
      prognostic significance of RASSF10 in CRC.Quantitative real-time polymerase chain
      reaction was used to detect the messenger RNA (mRNA) expression while enzyme
      linked immunosorbent assay was taken to measure the protein expression of RASSF10
      in tumor tissues and adjacent normal tissues from 102 patients with CRC. The
      relationship between RASSF10 expression level and clinical characteristics of CRC
      patients was analyzed by chi-squared test. In addition, the association between
      overall survival of CRC patients and RASSF10 expression was estimated by Kaplan
      Meier analysis. Cox regression analysis was used to evaluate the prognostic value
      of RASSF10.The expression level of RASSF10 in tumor tissues was significantly
      lower than that in the normal tissues both at mRNA and protein levels. Moreover,
      the expression level was correlated with lymph-node-metastasis and tumor-node
      metastasis stage. Kaplan-Meier analysis suggested that patients with high
      expression level of RASSF10 had a longer overall survival than those with low
      level (log-rank test, P < .001). Besides, RASSF10 might be a potential biomarker
      in the prognosis of CRC according to cox regression analysis.The down regulated
      of RASSF10 is found in CRC and it may be an ideal prognostic marker.

PMID- 29049168
TI  - Sialocutaneous fistula to the external auditory canal repaired with superficial
      parotidectomy and temporoparietal flap: A case report.
AB  - RATIONALE: Gustatory otorrhea can lead to cutaneous changes, recurrent infection,
      and social disruption. We present a case of a late, evolving sialocutaneous
      fistula to the external auditory canal, managed surgically after failing
      conservative therapies. This case is unique by late evolution, whereby the
      symptoms presented with significance 27 years after her operation and 19 years
      after mild symptoms initially arose. PATIENT CONCERNS: Gustatory, left-sided
      clear otorrhea with acutely increased volume over 8 months causing social
      disruption. DIAGNOSES: Sialocutaneous fistula to the external auditory canal.
      INTERVENTIONS: Superficial parotidectomy and temporoparietal flap for closure of
      fistula. OUTCOMES: No postoperative complications and resolution of gustatory
      otorrhea at one-year follow-up. LESSONS: This rare, but important, postoperative
      complication can present late with evolving symptoms, causing significant social
      disruption. It can be treated with conservative medical management and several
      surgical approaches.

PMID- 29049169
TI  - Association between plasminogen activator inhibitor gene polymorphisms and
      osteonecrosis of the femoral head susceptibility: A case-control study.
AB  - This study aimed to analyze the correlation of the plasminogen activator
      inhibitor (PAI-1) gene polymorphisms (rs6092 and rs7242) with susceptibility of
      osteonecrosis of the femoral head (ONFH).This case-control study included 106
      ONFH patients and 151 healthy controls. PAI-1 polymorphisms were genotyped by
      polymerase chain reaction (PCR) with direct sequencing. The genotype distribution
      of polymorphism in the control group was checked with the status of Hardy
      Weinberg equilibrium (HWE). The chi test was applied to compare the genotypes of
      polymorphisms between the case and control groups. The association intensity
      between PAI-1 polymorphisms and ONFH risk was estimated by odds ratios (ORs) and
      95% confidence intervals (95% CI). The linkage disequilibrium of PAI-1
      polymorphisms was analyzed by Haploview.We found that the genotypes and alleles
      of PAI-1 rs6092 and rs7242 polymorphisms had no obvious association with the risk
      of ONFH (P >.05). But the strong linkage disequilibrium existed between rs6092
      and rs7242 polymorphisms and haplotype G-T was significantly associated with the
      decreased risk of ONFH occurrence (OR = 0.666, 95%CI = 0.445-0.998).PAI-1 rs6092
      and rs7242 polymorphisms are not associated with ONFH development, but haplotype
      G-T may be a protective factor of ONFH.

PMID- 29049170
TI  - Case report of a congenital duodenal transverse septum causing partial
      obstruction.
AB  - INTRODUCTION: Duodenal obstructions caused by congenital anatomic abnormalities
      are rare in adults. Several patients in whom the duodenal obstruction was caused
      by a congenital duodenal diaphragm have been described. The duodenal obstruction
      in the patient presented herein was caused by a transverse septum, which has not
      been previously reported. A transverse septum is usually observed in the vagina;
      those involving the digestive tract have been rarely observed. CASE PRESENTATION:
      We herein report a case involving a 69-year-old woman with a congenital duodenal
      transverse septum causing partial obstruction. She was admitted to our hospital
      with a 3-month history of epigastric pain and vomiting. Upper gastrointestinal
      endoscopy, iodinated water-soluble contrast imaging, and abdominal computed
      tomography revealed dilation of the stomach and a neoplasm in the descending part
      of the duodenum. The patient was suspected to have a tumor in the descending part
      of the duodenum. Exploratory laparotomy showed a banded duodenal transverse
      septum at the junction of the second part of the duodenum. The duodenal
      transverse septum was approximately 2 mm thick and 1 cm wide and divided the
      duodenal lumen into 2 parts. The duodenal papillae were completely normal and
      located under the duodenal transverse septum. Histopathological analysis of the
      transverse septum showed that it was similar to the organizational structure of
      the duodenal wall. CONCLUSION: The possibility of congenital disease should be
      considered in older patients with intestinal obstruction, even when imaging
      studies reveal a duodenal neoplasm.

PMID- 29049171
TI  - Convex border of peripheral non-small cell lung cancer on CT images as a
      potential indicator of pleural invasion.
AB  - The aim of the study is to evaluate the use of the tumor border in peripheral non
      small cell lung cancer (NSCLC) as an indicator of pleural invasion.This
      retrospective study was performed at a single tertiary center. The analysis of
      136 patients with peripheral NSCLC included 101 (74.3%) patients with
      pathologically proven pleural invasion and 35 (25.7%) patients without pleural
      invasion. The tumor borders on conventional computed tomography (CT) were
      classified into 5 types on lung window setting: type 1, S or reverse S border
      with a blunt angle; type 2, sharp angle; type 3, concave border with a blunt
      angle; type 4, straight border with a perpendicular angle; and type 5, convex
      border with a perpendicular or blunt angle. In patients with more than 1 tumor
      border type, the priority was type 5, 4, 3, 2, and 1. Blunt angle, pleural
      contact >3 cm, and adjacent pleural thickening were also recorded for comparison
      with pleural invasion of peripheral tumors.Tumor border types 2 and 5
      significantly differed between patients with and without pleural invasion (P =
      .001 and P < .001, respectively). Patients with and without pleural invasion did
      not significantly differ in tumor border type 1, tumor border type 3, tumor
      border type 4, blunt angle, pleural contact >3 cm, or pleural thickening. Tumor
      border type 5 was a moderate indicator of pleural invasion with positive LR,
      5.20; accuracy, 57%; sensitivity, 45%; specificity, 91%; PPV, 94%; and NPV, 36%.
      Tumor border type 2 was a weak indicator of pleural invasion with positive LR,
      0.51; accuracy, 34%; sensitivity, 34%; specificity, 34%; PPV, 60%; and NPV,
      15%.Tumor border type 5 has a high PPV and high specificity for predicting
      pleural invasion by peripheral NSCLC.

PMID- 29049172
TI  - Primary cardiac angiosarcoma: A case report.
AB  - BACKGROUND: Primary cardiac angiosarcoma is rare, but it is the most aggressive
      type of cardiac malignant tumor. When disease is confirmed it is often late in
      its stage resulting in a poor prognosis. CASE PRESENTATION: We reported a 52-year
      old woman who complained of dyspnea for 2 months and dry cough for 10 days.
      Computed tomography (CT), F-fluorodeoxyglucose (F-FDG), positron emission
      tomography-computed tomography (PET-CT), and transthoracic echocardiography
      showed a space-occupying lesion 7 cm * 5 cm * 5 cm in the right atrium. Malignant
      cells can be seen in pericardial fluid by pericardiocentesis in local hospital,
      but not be diagnosed definitely. We conducted CT-guided biopsy of the tumor and
      observed the necrotic tissues. An exploratory thoracotomy was performed and
      histological examination confirmed angiosarcoma. Unable to be surgical excision
      due to infiltrating widely, the patients received chemotherapy with docetaxel for
      2 cycles and the disease was progressive. Antiangiogenesis-targeted therapy was
      combined with chemotherapy for 3 months. Unfortunately, the tumor was still in
      progress. She died of respiratory failure, survived for 10 months. CONCLUSION: It
      is difficult to diagnose the primary cardiac angiosarcoma in early stage.
      Chemotherapy and target therapy are very limited in this case. Surgery remains
      the preferred treatment for patients with primary cardiac angiosarcoma. More
      efforts should be carried out on the effective diagnosis and multimodality
      treatment for this malignant disease.

PMID- 29049173
TI  - The influence of caveolin-1 gene polymorphisms on hepatitis B virus-related
      hepatocellular carcinoma susceptibility in Chinese Han population: A case-control
      study.
AB  - This study aimed to explore the genetic association of polymorphisms in caveolin
      1 gene (CAV1) with hepatitis B virus-related hepatocellular carcinoma (HBV
      related HCC) susceptibility in a Chinese Han population.The genotyping of
      polymorphism was conducted using polymerase chain reaction-restriction fragment
      length polymorphism method. Whether the genotype distribution of polymorphisms in
      the healthy controls was consistent with Hardy-Weinberg equilibrium (HWE) was
      detected. The genotype and allele frequency difference between the 2 groups was
      compared by chi-square test. Odds ratio (OR) and 95% confidence interval (95% CI)
      were calculated to show the relative risk of HCC which resulted from genetic
      variants in CAV1. Moreover, the linkage disequilibrium of CAV1 polymorphisms was
      analyzed by Haploview.The AG genotype and A allele of rs1049334 showed
      significantly higher frequency in HCC patients than that of chronic HBV patients
      and the healthy controls (P < .05); so their carriage obviously increased the
      susceptibility to HBV-related HCC, irrespective of the fact whether individuals
      were infected with hepatitis B virus or not (AG vs GG: OR 1.958, 95% CI 1.050
      3.650, OR 1.899, 95% CI 1.034-3.487; A vs G: OR 1.667, 95% CI 1.033-2.689, OR
      1.777, 95% CI 1.103-2.863). Additionally, A-G haplotype of rs3807989-rs1049334
      showed the protective role for HBV-related HCC (OR 0.102, 95% CI 0.035-0.293; OR
      0.135, 95% CI 0.046-0.395).CAV1 rs1049334 polymorphism is significantly
      associated with the occurrence risk of HBV-related HCC, and the interaction of
      polymorphisms should not be neglected.

PMID- 29049174
TI  - Value of shear wave elastography in discriminating malignant and benign breast
      lesions: A meta-analysis.
AB  - The analysis was aimed to evaluate the diagnostic accuracy of shear wave
      elastography (SWE) for malignant breast lesions through a meta-analysis.Related
      articles were searched from Pubmed, Embase, and Cochrane library. Overall
      sensitivity and specificity were analyzed with DerSimonian and Laird random
      effects model. Area under curve with corresponding 95% confidence interval (were
      calculated to evaluate the diagnostic accuracy of SWE. Sensitivity and
      publication bias were assessed as well.A total of 25 articles including 4128
      patients and 4546 breast lesions were included in the pooled analysis. In the
      subgroup analysis, diagnostic sensitivity and specificity of SWE in Asian
      population were 0.84 (0.79-0.88) and 0.87 (0.84-0.90), respectively, whereas they
      were 0.92 (0.86-0.96) and 0.89 (0.84-0.92) in Caucasian population. The
      diagnostic accuracy of SWE was a little higher for Caucasians than for Asians
      (0.95 vs. 0.92). The diagnostic sensitivity and specificity of virtual touch
      tissue quantification were 0.85 (0.77-0.91) and 0.93 (0.88-0.96), respectively.
      It showed a little higher value in specificity and summary ROC curve than SWE
      (0.93 vs. 0.87; 0.95 vs. 0.93). In addition, maximum stiffness exhibited higher
      detection sensitivity than that of mean stiffness (0.91 vs. 0.85).SWE serves as
      an accurate diagnostic technology for discriminating between malignant and benign
      breast lesions.

PMID- 29049175
TI  - Retrospective analysis for the false positive diagnosis of PET-CT scan in lung
      cancer patients.
AB  - Early diagnosis is pivotal for prognosis of lung cancer patients. Positron
      emission tomography/computed tomography (PET-CT) is a useful method for human
      cancer diagnosis. In this study, we aimed to explore the false positive diagnosis
      of PET-CT in lung cancerIn total, 754 patients diagnosed with lung cancer via PET
      CT were retrospectively collected in this study. Histopathological detection
      served as gold standard. The diagnostic accuracy of PET-CT was defined as the
      proportion of lung cancer cases confirmed by pathological diagnosis in the study
      subjects, and the percentages of misdiagnosed cases represented the false
      positive diagnosis of PET-CT. Chi-square test and logistic regression analysis
      were used to analyze the association of pathologically confirmed result with
      clinical characteristics.Among all the patients, 705 cases were pathologically
      confirmed with lung cancer. The diagnostic accuracy of PET-CT was 93.5%, and the
      false positive rate was 6.50%. Among the false positive patients, inflammatory
      pseudotumor (42.86%) and tuberculoma (36.74%) were the most pathological types.
      In the positive detection group, adenocarcinoma (57.16%) and squamous carcinoma
      (33.19%) were the main pathological types, and 68.09% of the lung cancer patients
      were at the advanced stages. The false positive rate were related with age,
      diabetes, interleukin-6 (IL-6) level, and T-spot test (all P < .05).PET-CT could
      be a good diagnostic method for lung cancer, but the false positive cases could
      appear. Detection of inflammatory indicators such as IL-6 and T-spot TB test may
      help improve the diagnostic accuracy of PET-CT.

PMID- 29049176
TI  - Correlation of PON1 polymorphisms with ankylosing spondylitis susceptibility: A
      case-control study in Chinese Han population.
AB  - Paraoxonase 1 (PON1) modulates the oxidative stress and inflammatory response,
      thus, it might relate to the risk of ankylosing spondylitis (AS). The aim of
      present study was to discover the correlation of PON1 polymorphisms (rs662 and
      rs854560) with PON1 activity and AS risk.Around 128 AS patients and 146 healthy
      controls were recruited in this case-control study. PON1 polymorphisms were
      genotyped by direct sequencing. Serum PON1 activity was detected and compared by
      nonparametric test in different genotypes of PON1 polymorphisms. Odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated to present the relative
      risk for AS.GG genotype and G allele of rs662 polymorphism were closely
      correlated with enhanced AS risk (P = .034, OR = 2.318, 95%CI = 1.051-5.113; P =
      .032, OR = 1.485, 95%CI = 1.033-2.135). PON1 activity was obviously higher in
      controls than that in AS patients. Significant difference of PON1 activity has
      been discovered in the different rs662 genotypes (P < .01). rs662 GG genotype
      carriers had the lowest PON1 activity, followed by AG carriers and the AA
      carriers. Besides, no significant relationship existed between rs854560 genotypes
      and AS risk.PON1 rs662 polymorphism is significantly correlated with increased AS
      risk via inhibiting PON1 activity.

PMID- 29049177
TI  - Association of BMP-14 rs143383 ploymorphism with its susceptibility to
      osteoarthritis: A meta-analysis and systematic review according to PRISMA
      guideline.
AB  - BACKGROUND: Osteoarthritis (OA) is a complex disease which can be caused by both
      environmental and genetic factors. A functional locus rs143383 of bone
      morphogenetic protein-14 (BMP-14) has been pointed out to be associated with OA
      etiology, but conflicting conclusions have been reached. To provide a more
      comprehensive conclusion about this issue, we performed this meta-analysis.
      METHODS: Relevant studies were searched from electronic databases including
      PubMed, Chinese National Knowledge Infrastructure, Embase, and Wanfang. The
      strength of correlations was examined with pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs). Subgroup analyses stratified by ethnicity and
      source of control were carried out. All statistical analyses were performed with
      STATA software (version 12.0). RESULTS: Overall, BMP-14 rs143383 polymorphism was
      negatively correlated with the susceptibility to knee OA and hand OA under
      genetic contrasts of CC versus TT, CC + TC versus TT, CC versus TT + TC, C versus
      T, TC versus TT (OR = 0.71, 95% CI = 0.65-0.79; OR = 0.81, 95% CI = 0.73-0.89; OR
      = 0.79, 95% CI = 0.71-0.86; OR = 0.85, 95% CI = 0.81-0.90; OR = 0.84, 95% CI =
      0.75-0.93), and TC versus TT, CC versus TT + TC, C versus T (OR = 0.76, 95% CI =
      0.65-0.89; OR = 0.79, 95% CI = 0.68-0.92; OR = 0.90, 95% CI = 0.85-0.95),
      respectively; similar results were observed in subgroups after stratification
      analyses. Additionally, the polymorphism also reduced hip OA risk in Asian group
      after stratified analysis by ethnicity. CONCLUSION: BMP-14 rs143383 polymorphism
      may be a protective factor against OA occurrence.

PMID- 29049178
TI  - Evaluation of smoking cessation intervention in patients with chronic diseases in
      smoking cessation clinics.
AB  - This study aimed to evaluate the effects of psychological intervention and
      psychological plus drug intervention on smoking cessation among male smokers with
      single chronic diseases.A total of 509 male smokers were divided into
      psychological group (n = 290) and psychological plus drugs (n = 219) groups
      according to their will. The physicians provided free individual counseling and
      follow-up interviews with brief counseling for all the subjects. In addition to
      mental intervention, patients in psychological plus drug group also received
      bupropion hydrochloride or varenicline tartrate to quit smoking. Outcomes were
      self-reported, regarding the 7-day point prevalence on abstinence rate and
      continuous abstinence rates at 1-, 3-, and 6-month follow-up period. Data
      analyses were performed using intention-to-treat analysis and per protocol
      analysis.With regards to the 3 follow-up time points, 7-day point-prevalence
      abstinence rate in psychological plus drugs group was all higher than that in the
      psychological intervention group. Additionally, the 3-month continuous abstinence
      rate (21.4%) of the 6-month follow-up in the psychological group was not
      significantly higher than that (26.9%) in the psychological plus drugs group (P
      >.05 for all). Fagerstrom test score, stage of quitting smoking, perceived
      confidence or difficulty in quitting, and chronic disease types were
      independently correlated with 3-month continuous abstinence in the 6-month follow
      up (P <.05 for all). The results were similar between intentional analysis and
      protocol analysis.The psychological intervention and psychological plus drugs
      intervention exerted good effects on smoking cessation in a short time (1 month).
      Nevertheless, the advantages did not appear during long-time (6 months) follow
      up.

PMID- 29049179
TI  - Genetic polymorphisms of NAT2 and risk of acute myeloid leukemia: A case-control
      study.
AB  - Our purpose was to investigate the possible associations between N
      acetyltransferase-2 (NAT2) gene polymorphisms and the risk of acute myeloid
      leukemia (AML) in Chinese Han population.A case-control study was conducted
      including 98 AML cases and 112 healthy controls. NAT2 gene 2 polymorphisms
      rs1799930 and rs1799931 were genotyped using direct sequencing. Chi-square test
      was performed to compare the genotype and allele distribution differences between
      groups. Odds ratio (OR) with 95% confidence interval (CI) was calculated to
      estimate the association between NAT2 gene polymorphisms and AML onset.A
      remarkable decrease trend of rs1799931 GA genotype was detected in AML patients
      compared with controls, whereas the ancestral GG genotype frequency increased in
      cases (P < .05). And the mutant A allele of rs1799931 significantly reduced the
      risk of AML by 0.585-fold versus the ancestral G allele carriers (OR = 0.585, 95%
      CI = 0.361-0.950). But the distributions of rs1799930 genotype and allele were
      similar between groups (P > .05).Our findings suggested that NAT2 gene
      polymorphism rs1799931 was associated with decreased risk of AML and was likely
      to be a protective factor against AML development.

PMID- 29049180
TI  - The effect of care intervention for obese patients with type II diabetes.
AB  - The incidence of type II diabetes mellitus (T2DM) is increasing worldwide and
      affecting the quality of people's life. This study was designed to evaluate the
      effect of care intervention on body weight and glycemic parameters in obese T2DM
      patients.One hundred twenty-six obese T2DM cases were randomly divided into 2
      groups. Patients in control group received conventional care, while patients in
      the intervention group received dietary, exercise, and psychology interventions
      on the basis of conventional care. Twelve months follow-up was performed to
      compare the changes of body weight and glycemic parameters in the 2 groups.There
      were 119 patients completing the research, 60 in the intervention group and 59 in
      control group. The levels of fasting plasma glucose (FPG), 2 hours postprandial
      blood glucose (PBG2 h), hemoglobin A1c (HbA1c), and aldose reductase (AR) were
      all significantly decreased (all, P < .05) in intervention group compared with
      the control group after 12 months follow-up. Moreover, the body weight and BMI
      (body mass index) were also significantly reduced in intervention group, and the
      weight loss was significantly higher in intervention group than that in control
      group during the follow-up.To implement care intervention for obese T2DM patients
      could strengthen the management of blood glucose, reduce body weight and
      complications.

PMID- 29049181
TI  - Recurrent multiple-organ involvement of disseminated alveolar echinococcosis in 3
      patients: Case report.
AB  - RATIONALE: Alveolar echinococcosis (AE) is a rare but highly malignant form of
      echinococcosis caused by Echinococcus multilocularis. There have been very few
      reports on multiple-organ AE, especially AE in bones. Here we report 3 rare cases
      of disseminated multiple-organ AE from western China and its neighboring areas.
      PATIENT CONCERNS: Patient 1 had back and left hip pain, headache, and weakness in
      left lower limb, often with minor epilepsy and fluctuation of blood pressure.
      Lower limbs Babinski sign was positive and muscular tension was above normal
      range. The second patient had pain in lower limbs and chest discomfort without
      fever, cough, sputum, chest tightness, or hemoptysis. Patient 3 had masses and
      pain in the back side of his right shoulder. DIAGNOSES: The patients had been
      treated for AE multiple times and were positive for serum hydatid antigens. They
      were diagnosed as multiorgan AE involving liver, spinal cord, and many other
      organs. INTERVENTIONS: The patients had undergone surgeries to decompress the
      spinal cord, remove lesions from tissues as required, and were put on albendazole
      for at least 2 years. OUTCOMES: The patients responded well and AE recurrence has
      not occurred. LESSONS: All 3 cases experienced multiple recurrences of AE due to
      missed diagnosis, misdiagnosis, or inappropriate treatment, which resulted in
      metastatic multiorgan AE. These cases demonstrated the need for more policy
      attention to battle AE endemic in western China.

PMID- 29049182
TI  - Endovascular treatment of Brucella-infected abdominal aortic aneurysm: A case
      report.
AB  - RATIONALE: In very rare cases, a primary infected abdominal aortic aneurysm
      (IAAA) is caused by a species of Brucella. In this report, we report such a case
      that was successfully treated with a novel approach. To the best of our
      knowledge, this was the first case occurring in China, in which an infection of
      the abdominal aortic aneurysm was caused by a Brucella species. PATIENT CONCERNS:
      The clinical findings included high fever, fatigue, and abdominal pain.
      DIAGNOSES: The diagnosis was confirmed by computed tomography angiography and by
      bacteriologic isolation from the patient's blood culture. INTERVENTIONS: The
      patient was given endovascular aneurysm repair (EVAR) and Brucella-sensitive
      antibiotics for 6 weeks. OUTCOMES: During the 10-month follow-up, the patient's
      clinical course remained uneventful. LESSONS: Our case study supports the premise
      that endovascular aneurysm repair is an appropriate alternative strategy to treat
      an infected abdominal aortic aneurysm. Compared with conventional surgical
      treatment, EVAR with long-term oral antibiotics is a simpler, less traumatic, and
      more efficient procedure. However, this needs to be further evaluated through
      long-term follow-up.

PMID- 29049183
TI  - Identifying key genes associated with acute myocardial infarction.
AB  - BACKGROUND: This study aimed to identify key genes associated with acute
      myocardial infarction (AMI) by reanalyzing microarray data. METHODS: Three gene
      expression profile datasets GSE66360, GSE34198, and GSE48060 were downloaded from
      GEO database. After data preprocessing, genes without heterogeneity across
      different platforms were subjected to differential expression analysis between
      the AMI group and the control group using metaDE package. P < .05 was used as the
      cutoff for a differentially expressed gene (DEG). The expression data matrices of
      DEGs were imported in ReactomeFIViz to construct a gene functional interaction
      (FI) network. Then, DEGs in each module were subjected to pathway enrichment
      analysis using DAVID. MiRNAs and transcription factors predicted to regulate
      target DEGs were identified. Quantitative real-time polymerase chain reaction (RT
      PCR) was applied to verify the expression of genes. RESULT: A total of 913
      upregulated genes and 1060 downregulated genes were identified in the AMI group.
      A FI network consists of 21 modules and DEGs in 12 modules were significantly
      enriched in pathways. The transcription factor-miRNA-gene network contains 2
      transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa-miR-30c
      5p. RT-PCR validations showed that expression levels of FOXO3 and MYBL2 were
      significantly increased in AMI, and expression levels of hsa-miR-21-5p and hsa
      miR-30c-5p were obviously decreased in AMI. CONCLUSION: A total of 41 DEGs, such
      as SOCS3, VAPA, and COL5A2, are speculated to have roles in the pathogenesis of
      AMI; 2 transcription factors FOXO3 and MYBL2, and 2 miRNAs hsa-miR-21-5p and hsa
      miR-30c-5p may be involved in the regulation of the expression of these DEGs.

PMID- 29049184
TI  - Epidemiology, clinical characteristics, and risk factors for mortality of early-
      and late-onset invasive candidiasis in intensive care units in China.
AB  - To identify the epidemiology, treatments, outcomes, and risk factors for patients
      with early- or late-onset invasive candidiasis (EOIC or LOIC) in intensive care
      units in China.Patients were classified as EOIC (<=10 days) or LOIC (>10 days)
      according to the time from hospital admission to IC onset to identify distinct
      clinical characteristics.There were 105 EOIC cases and 201 LOIC cases in this
      study. EOIC was related to more severe clinical conditions at ICU admission or
      prior to IC. Significantly, more cases of Candida parapsilosis infection were
      found in patients with LOIC than in those with EOIC. The mortality of EOIC was
      significantly lower than that for LOIC. Sequential Organ Failure Assessment
      (SOFA) score at ICI diagnosis in the EOIC group and the interval from ICU
      admission to ICI occurrence in the LOIC group were identified as risk factors for
      mortality. Susceptibility to the first-line agent was associated with a lower
      risk of mortality in the LOIC group.The mortality rate was significantly lower in
      the EOIC group, and there were more cases of non-albicans infection in the LOIC
      group. Susceptibility to the first-line agent was an important predictor of
      mortality in the LOIC group. SOFA score at ICI diagnosis in the EOIC group and
      interval from ICU admission to ICI occurrence in the LOIC group were identified
      as risk factors for mortality.

PMID- 29049185
TI  - Relationship between ADD1 Gly460Trp gene polymorphism and essential hypertension
      in Madeira Island.
AB  - Essential hypertension (EH) is a complex disease in which physiological,
      environmental, and genetic factors are involved in its genesis. The genetic
      variant of the alpha-adducin gene (ADD1) has been described as a risk factor for
      EH, but with controversial results.The objective of this study was to evaluate
      the association of ADD1 (Gly460Trp) gene polymorphism with the EH risk in a
      population from Madeira Island.A case-control study with 1614 individuals of
      Caucasian origin was performed, including 817 individuals with EH and 797
      controls. Cases and controls were matched for sex and age, by frequency-matching
      method. All participants collected blood for biochemical and genotypic analysis
      for the Gly460Trp polymorphism. We further investigated which variables were
      independently associated to EH, and, consequently, analyzed their interactions.In
      our study, we found a significant association between the ADD1 gene polymorphism
      and EH (odds ratio 2.484, P = .01). This association remained statistically
      significant after the multivariate analysis (odds ratio 2.548, P = .02).The ADD1
      Gly460Trp gene polymorphism is significantly and independently associated with EH
      risk in our population. The knowledge of genetic polymorphisms associated with EH
      is of paramount importance because it leads to a better understanding of the
      etiology and pathophysiology of this pathology.

PMID- 29049186
TI  - Combined laparoscopic and open technique for repair of congenital abdominal
      hernia: A case report of prune belly syndrome.
AB  - BACKGROUND: Prune belly syndrome (PBS) is a rare congenital disorder among
      adults, and the way for repairing abdominal wall musculature has no unified
      standard. MATERIALS AND METHODS: We described combining laparoscopic and open
      technique in an adult male who presented with PBS. Physical examination and
      radiological imaging verified the case of PBS. The deficiency of abdominal wall
      musculature was repaired by combining laparoscopic and open technique using a
      double-deck complex patch. RESULTS: The patient successfully underwent abdominal
      wall repair by combining laparoscopic and open technique. Postoperative recovery
      was uneventful, and improvement in symptom was significant in follow-up after 3,
      6, 12, and 24 months. CONCLUSIONS: Combining laparoscopic and open technique for
      repair of deficiency of abdominal wall musculature in PBS was an exploratory way
      to improve life quality.

PMID- 29049187
TI  - A myeloid sarcoma involving the small intestine, kidneys, mesentery, and
      mesenteric lymph nodes: A case report and literature review.
AB  - RATIONALE: Myeloid sarcomas (MSs) are rare malignant hematological tumors. They
      most commonly occur in patients with acute or chronic myeloid leukemia. A de novo
      MS with no evidence of blood system disease is rare, but may represent the first
      sign of a systemic illness that precedes a full-blown disease. Herein, we report
      the computed tomography (CT) findings of an extremely rare case of a nonleukemic
      MS that progressed to acute myelogenous leukemia (AML) and simultaneously
      involved the small intestine, kidneys, mesentery, and mesenteric lymph nodes.
      Moreover, we provide CT findings before and after AML chemotherapy, which have
      not been reported previously. PATIENT CONCERNS: A 25-year-old man with
      intermittent upper abdominal pain for 6 months was admitted to the hospital on
      November 28, 2015. Initial CT showed concentric wall thickening of the jejunum
      with an adjacent mesenteric soft tissue mass and mesenteric lymph nodes
      enlargement. Both kidneys were involved as indicated by the presence of well
      defined mildly dilated lesions. During the laparoscopic surgery, the small
      intestinal tumor, mesenteric soft tissue mass, and mesenteric lymph nodes were
      removed. DIAGNOSES: The pathological diagnosis was an MS. INTERVENTIONS: The
      patient refused systemic chemotherapy and was rehospitalized with persistently
      aggravated abdominal distension on February 17, 2016. Follow-up CT showed diffuse
      small bowel wall thickening, widespread infiltration of the peritoneum, omentum,
      and mesentery, mesenteric lymph node enlargement, and large amounts of ascites
      fluid. The lesions in both kidneys were substantially larger and more numerous
      than on initial CT. Then the patient was treated with conventional AML
      chemotherapy. OUTCOMES: The patient achieved complete hematological remission on
      bone marrow examination. Follow-up CT in September 4, 2016, showed none of the
      abnormalities seen on initial CT. Currently, the patient is in complete
      remission. LESSONS: If the radiological examination shows lesions at multiple
      sites, and these lesions are soft tissue masses with homogenous enhancement, MS
      should be considered in the differential diagnosis, and an aspiration biopsy
      should be performed to provide a definitive pathological diagnosis. If MS is
      diagnosed, systemic chemotherapy is crucial to recovery; otherwise, the disease
      may progress rapidly. Medical imaging is helpful for diagnosing MS and for
      monitoring treatment response.

PMID- 29049188
TI  - Incidence of venous thromboembolism following the neoadjuvant chemotherapy
      regimen for epithelial type of ovarian cancer.
AB  - This study aims to analyze the risk of venous thromboembolism (VTE) in patients
      receiving neoadjuvant chemotherapy (NACT) for epithelial ovarian cancer (EOC).A
      retrospective audit was conducted examining 147 patients treated for EOC.
      Surgical treatment with curative intent, with or without NACT and adjuvant
      chemotherapy, is the treatment approach, which was modified according to the
      patient's condition. The incidence of VTE with the most commonly used
      chemotherapy regimen, carboplatin, cisplatin, paclitaxel, docetaxel, and others
      were evaluated.This study found a 13.6% incidence of VTE in patients undergoing
      therapy with curative intent for EOC. No association was seen between NACT and
      VTE compared to VTE after standard treatment: 2/16 (12.5%) vs 5/131 (3.8%) (P =
      .16). Univariate and multivariate analyses also demonstrated that NACT has no
      risk for VTE with odds ratio (OR) = 0.89 (95% CI = 0.18-4.28) and P = 1. Results
      did not vary significantly with the type of chemotherapy used. Furthermore,
      increased incidence of VTE as an incidental finding supports the well-established
      role of malignancy in VTE occurrence. Univariate and multivariate analyses
      demonstrated that VTE occurred more frequently in menopausal women than
      nonmenopausal women (17.9% vs 5.8%) with OR = 3.55 (95% CI = 0.99-12.78) and P =
      .04 in patients aged >=60 (19.3% vs 10%) with OR = 2.15 (95% CI = 0.83-5.57) and
      P = .13 but is not statistically significant.We conclude that NACT has no
      association with VTE and the currently used common chemotherapeutic drug
      combinations for ovarian cancer carry the minimal risk of thromboembolic events.

PMID- 29049189
TI  - The prevalence and long-term variation of hospital readmission for patients with
      diabetes in Tianjin, China: A cross-sectional study.
AB  - Little is known about hospital readmission for patients with diabetes in China.
      We aimed to assess the temporal pattern, risk factors, and variations of all
      cause readmission among hospitalized patients with diabetes in Tianjin, China,
      from 2008 to 2013.The Tianjin Basic Medical Insurance Register System database
      was used to identify discharged patients with diabetes from 2008 to 2013. The
      influential factors and trends of rehospitalization were analyzed for 30-, 60-
      and 90-day predicted readmission rates. The Blinder-Oaxaca decomposition was used
      to explain the readmission variations between 2008 and 2013.The long stay-time at
      the index hospitalization is a shared risk factor for readmission at 30, 60, and
      90 days each year. The 90-day predicted readmission rates were the highest for
      each year (all P < .001). The adjusted readmission rates generally decreased by
      year (all P < .001), except for at the 90-day interval, which decreased in 2010
      and slightly increased in 2013 (from 7.47% in 2012 to 7.65% in 2013). If the
      patients had been readmitted to the hospital in 2013 and the only changes that
      had occurred since 2008 were observable characteristics, then the readmission
      rates would have decreased by 0.84%, 0.27%, and 0.18% at 30, 60, and 90 days,
      respectively. The potential policy changes decreased the readmission rates at
      1.35%, 2.01%, and 1.04% for the 3 intervals, respectively.Identifying targeted
      factors for the decrease in readmission rates may help to control readmission,
      particularly for long-interval patients.

PMID- 29049190
TI  - Chronic active Epstein-Barr virus infection as the initial symptom in a Janus
      kinase 3 deficiency child: Case report and literature review.
AB  - RATIONALE: With the progress of sequencing technology, an increasing number of
      atypical primary immunodeficiency (PID) patients have been discovered, including
      Janus kinase 3 (JAK3) gene deficiency. PATIENT CONCERNS: We report a patient who
      presented with chronic active Epstein-Barr virus (CAEBV) infection but responded
      poorly to treatment with ganciclovir. DIAGNOSES: Next-generation sequencing (NGS)
      was performed, including all known PID genes, after which Sanger sequencing was
      performed to verify the results. Genetic analysis revealed that our patient had 2
      novel compound heterozygous mutations of JAK3, a gene previously reported to
      cause a rare form of autosomal recessive severe combined immunodeficiency with
      recurrent infections. The p.H27Q mutation came from his father, while p. R222H
      from his mother. Thus, his diagnosis was corrected for JAK3-deficiency PID and
      CAEBV. INTERVENTIONS: Maintenance treatment of subcutaneous injection of
      recombinant human interferon alpha-2a was given to our patient with 2 MU, 3 times
      a week. OUTCOMES: Interferon alpha was applied and the EBV infection was
      gradually controlled and his symptoms ameliorated remarkably. Our patient is in
      good health now and did not have relapses. LESSONS: The diagnoses of PID should
      be taken into consideration when CAEBV patients respond poorly to conventional
      treatments. Good results of our patient indicate that interferon alpha-2a may be
      an alternative treatment for those who are unwilling to accept hematopoietic stem
      cell transplantation (HSCT) like our patient. Literature review identified 59
      additional cases of JAK3 deficiency with various infections.

PMID- 29049191
TI  - Significance of monitoring plasma concentration of voriconazole in a patient with
      liver failure: A case report.
AB  - RATIONALE: Invasive pulmonary aspergillosis is associated with significant
      morbidity and mortality in patients with liver failure. Voriconazole (VRCZ) is
      recommended as a primary therapeutic agent for the treatment of invasive
      aspergillosis and metabolized in the liver. Now, data are still lacking on the
      safety and appropriate dosage of VRCZ in patients with liver failure. Here, we
      report a representative case of invasive pulmonary fungal infection in a patient
      with liver failure who was treated with low-dose VRCZ. PATIENT CONCERNS: A 21
      year-old man, presented with subacute liver failure caused suspected by viral
      infection, was admitted on June 22, 2014. Liver function was not improved by the
      treatment of gancicolovir and methylprednisolone. The patient presented with
      fever, cough, and hyperpyrexia on July 14. Laboratory tests revealed raised
      neutrophil percentage (82.1%, normal range [NR] 50-70), international normalized
      ratio (INR) (2.32, NR 0.8-1.2) and levels of serum lactic acid (4.308 mmol/L, NR
      0.6-2.2), alanine transaminase (165 U/L,NR 0-40), aspartate transaminase (99 U/L,
      NR 8-40), and total bilirubin (654 mmol/L, NR 3.4-20.5). Furthermore, CD4+ T
      cell, CD8+T cell, and B cell count were low (169, 221, and l8/mL, respectively).
      Sputum smear microscopy for bacteria was negative, but the direct observation for
      fungal elements was positive. Thoracic CT scan revealed bilateral pulmonary high
      density shadow. Sputum cultures were positive 2 days later with the presence of
      Aspergillus fumigatus. DIAGNOSES: Therefore, this patient diagnosed with
      suspected pulmonary a spergillosis. INTERVENTIONS: VRCZ was used on July 15th and
      its dosage was 400 mg twice on day 1 followed by a maintenance dose of 100 mg
      twice daily according to drug usage instruction. However, some side effects, such
      as tremors, lips twitching, and hair loss, occurred. Plasma VRCZ trough
      concentration was 8.1 mg/mL which was much higher than the recommend level.
      Therefore, VRCZ dosage was adjusted according to its plasma concentration. VRCZ
      plasma concentration fluctuated between 2.5 to 4.7 mg/mL when its dosage was 100
      mg once daily and side effects disappeared. OUTCOMES: VRCZ was administered for 2
      months. This patient's symptoms and liver function were improved. A follow-up CT
      scan performed at the end of VRCZ therapy indicated that the high-density shadow
      had diminished. LESSONS: This case demonstrated that low-dose VRCZ (maintenance
      dose, 100 mg/day) can achieve effective plasma concentration and reduce side
      effects without liver damage. We believe that VRCZ is safe to be administered in
      patients with liver failure, but its plasma concentration should be carefully
      monitored.

PMID- 29049192
TI  - Effect of alcohol intoxication on the risk of venous thromboembolism: A
      nationwide retrospective cohort study.
AB  - This study investigated whether alcohol intoxication (AI) increases the risk of
      venous thromboembolism (VTE) by using the Taiwan National Health Insurance
      Research Database (NHIRD).Using data from the NHIRD, we assembled 61,229 patients
      with acute AI and randomly selected 244,916 controls. Each patient was monitored
      from 2000 to 2011 to identify those who were subsequently diagnosed with deep
      vein thrombosis (DVT) and pulmonary embolism (PE). Cox proportional hazard
      regression analysis was conducted to determine the risk of VTE in the patients
      with AI compared with the controls.The incidence rate of DVT during the 10 years
      follow-up period was 9.36 per 10,000 person-years and 2.07 per 10,000 person
      years in the AI and non-AI cohorts, respectively. Moreover, the incidence rate of
      PE was 4 per 10,000 person-years in the AI cohort and 0.93 in the non-AI cohort.
      After adjustment for age, sex, and comorbidities, the risks of DVT and PE were
      3.40 [95% confidence interval (CI) = 2.83-4.08] and 3.53 (95% CI = 2.69-4.65)
      fold higher in the AI cohort than in the non-AI cohort.An increased incidence of
      VTE was observed among patients with AI. Therefore, physicians should carefully
      estimate the risk of VTE in patients with AI.

PMID- 29049194
TI  - Effects of action observation therapy on upper extremity function, daily
      activities and motion evoked potential in cerebral infarction patients.
AB  - BACKGROUND: The aim of this study was to explore the effects of action
      observation therapy on motor function of upper extremity, activities of daily
      living, and motion evoked potential in cerebral infarction patients. METHOD:
      Cerebral infarction survivors were randomly assigned to an experimental group (28
      patients) or a control group (25 patients). The conventional rehabilitation
      treatments were applied in both groups, but the experimental group received an
      additional action observation therapy for 8 weeks (6 times per week, 20 minutes
      per time). Fugl-Meyer assessment (FMA), Wolf Motor Function Test (WMFT), Modified
      Barthel Index (MBI), and motor evoked potential (MEP) were used to evaluate the
      upper limb movement function and daily life activity. RESULTS: There were no
      significant differences between experiment and control group in the indexes,
      including FMA, WMFT, and MBI scores, before the intervention. However, after 8
      weeks treatments, these indexes were improved significantly. MEP latency and
      center-motion conduction time (CMCT) decreased from 23.82 +/- 2.16 and 11.15 +/-
      1.68 to 22.69 +/- 2.11 and 10.12 +/- 1.46 ms. MEP amplitude increased from 0.61
      +/- 0.22 to 1.25 +/- 0.38 mV. A remarkable relationship between the evaluations
      indexes of MEP and FMA was found. CONCLUSIONS: Combination of motion observation
      and traditional upper limb rehabilitation treatment technology can significantly
      elevate the movement function of cerebral infarction patients in subacute seizure
      phase with upper limb dysfunction, which expanded the application range of motion
      observation therapy and provided an effective therapy strategy for upper
      extremities hemiplegia in stroke patients.

PMID- 29049193
TI  - Efficacy and safety of immunomodulatory drugs in patients with anterior uveitis:
      A systematic literature review.
AB  - BACKGROUND: To assess the efficacy and safety of immunomodulatory drugs in
      patients with noninfectious anterior uveitis (AU). METHODS: Systematic review of
      studies were retrieved from Medline (1961 to March 2016), Embase (1961 to March
      2016), and Cochrane Library (up to March 2016), and a complementary hand search
      was also performed. The selection criteria were as follows: (population)
      noninfectious AU patients, adults; (intervention) immunomodulatory drugs (any
      dose, regimen, route of administration, duration of treatment); (outcome) control
      of inflammation, steroid-sparing effect, AU flares, adverse events, and so on;
      (study design) systematic literature reviews, randomized controlled trials, and
      observational studies. The study quality was assessed using the Jadad scale and
      according to The Oxford Centre for Evidence-based Medicine (update 2009).
      RESULTS: We included 13 studies of moderate-poor quality, with a mean duration
      from 5 months to 20 years, and number of AU patients ranging from 9 to 274.
      Patient's demographic and clinical characteristics were very heterogeneous. In
      most cases, uveitis anatomic classification criteria and outcomes definitions
      were unclear. Some of the studies only included AU patients with a systemic
      disease associated, mostly spondyloarthritis, others, mixed populations
      (idiopathic and systemic disease associated patients), and in some articles this
      data is not described. We found that methotrexate, cyclosporine A, azathioprine,
      adalimumab, and golimumab might prevent AU flares, improve ocular inflammation
      and visual acuity, and decrease systemic steroids doses. CONCLUSIONS: Although
      there is a lack of robust evidence, methotrexate, cyclosporine A, azathioprine,
      adalimumab, and golimumab might be effective in AU patients.

PMID- 29049195
TI  - The efficacy of combined intra-articular and intravenous tranexamic acid for
      blood loss in primary total knee arthroplasty: A meta-analysis.
AB  - BACKGROUND: This meta-analysis aimed to illustrate the efficacy and safety of
      combined topical and intravenous (IV) tranexamic acid (TXA) for blood loss
      control in primary total knee arthroplasty (TKA) patients. METHODS: In April
      2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of
      Science, Cochrane Database of Systematic Reviews, and Google database. Data on
      patients prepared for TKA surgery in studies that compared combined topical and
      IV TXA versus placebo, topical, or IV TXA alone were retrieved. The primary
      endpoint was the need for transfusion, total blood loss, hemoglobin drop, and the
      occurrence of deep venous thrombosis (DVT), pulmonary embolism (PE), and the
      infection. After testing for publication bias and heterogeneity between studies,
      data were aggregated for random-effects models when necessary. RESULTS: Seven
      clinical studies were ultimately included in the meta-analysis. Compared with IV
      TXA and control group, combined TXA was associated with less need for
      transfusion, blood loss, and hemoglobin drop (P < .05). There was no significant
      difference between the combined TXA and topical TXA in terms of the need for
      transfusion, total blood loss, and hemoglobin drop (P > .05). There was no
      significant difference between the complications (DVT, PE, and infection) between
      the combined TXA, IV TXA, topical TXA, and control group. CONCLUSIONS: Current
      meta-analysis suggests that the combined IV and topical TXA was superior than IV
      TXA or control group. There is still need for more studies to identify whether
      combined TXA was superior than topical TXA alone.

PMID- 29049196
TI  - Three-dimensional reduction and finite element analysis improves the treatment of
      pelvic malunion reconstructive surgery: A case report.
AB  - RATIONALE: Pelvic malunion is a rare complication and is technically challenging
      to correct owing to the complex three-dimensional (3D) geometry of the pelvic
      girdle. Hence, precise preoperative planning is required to ensure appropriate
      correction. Reconstructive surgery is generally a 2- or 3-stage procedure, with
      transiliac osteotomy serving as an alternative to address limb length
      discrepancy. PATIENT CONCERNS: A 38-year-old female patient with a Mears type IV
      pelvic malunion with previous failed reconstructive surgery was admitted to our
      department due to progressive immobilization, increasing pain especially at the
      posterior pelvic arch and a leg length discrepancy. The leg discrepancy was
      approximately 4 cm and rotation of the right hip joint was associated with pain.
      DIAGNOSIS: Radiography and computer tomography (CT) revealed a hypertrophic
      malunion at the site of the previous posterior osteotomy (Mears type IV)
      involving the anterior and middle column, according to the 3-column concept, as
      well as malunion of the left anterior arch (Mears type IV). INTERVENTIONS: The
      surgery was planned virtually via 3D reconstruction, using the patient's CT, and
      subsequently performed via transiliac osteotomy and symphysiotomy. Finite element
      method (FEM) was used to plan the osteotomy and osteosynthesis as to include an
      estimation of the risk of implant failure. OUTCOMES: There was not incidence of
      neurological injury or infection, and the remaining leg length discrepancy was <=
      2 cm. The patient recovered independent, pain free, mobility. Virtual 3D planning
      provided a more precise measurement of correction parameters than radiographic
      based measurements. FEM analysis identified the highest risk for implant failure
      at the symphyseal plate osteosynthesis and the parasymphyseal screws. No implant
      failure was observed. LESSONS: Transiliac osteotomy, with additional osteotomy or
      symphysiotomy, was a suitable surgical procedure for the correction of pelvic
      malunion and provided adequate correction of leg length discrepancy. Virtual 3D
      planning enabled precise determination of correction parameters, with FEM
      analysis providing an appropriate method to predict areas of implant failure.

PMID- 29049197
TI  - Value of evaluating procalcitonin kinetics in diagnosis of infections in patients
      undergoing laparoscopic radical cystectomy.
AB  - Postsurgery infection is a common complication after laparoscopic radical
      cystectomy (LRC) followed by urinary diversion. White blood cell (WBC) values and
      C-reactive protein (CRP) are routinely used as markers for infection, but lack of
      specificity and their elevation is often delayed in clinically significant
      events. In this study, we aimed to investigate the value of procalcitonin (PCT)
      kinetics in assisting early diagnosis of infection in patients undergoing LRC.The
      patients' medical records between May 2013 and May 2016 were reviewed
      retrospectively. WBC, CRP, and PCT plasma levels as well as clinical symptoms
      were registered in 306 patients preoperatively (day 0), and 5 consecutive days
      postoperatively. Based on microbiological and clinical data, patients were
      grouped into noninfection- (NI-) and infection- (I-) groups. The day of new onset
      infection was observed were defined as day t0 and the day after that as day t1.
      For the NI-group, the day on which PCT was at the peak was defined as day t1 and
      the previous day as day t0.Of the 306 patients, 46 (15.03%) have proven
      infection. PCT levels were analogous at day t0:NI-group [median (interquartile
      range)]: 0.69(1.99) vs I-group [median (interquartile range)]: 1.0[0.75], P = .1.
      PCT levels were significantly increased at day t1 in the I-group[median
      (interquartile range)]:2.9(1.3) vs NI-group[median (interquartile range)]:
      1.3(1.5), P < .01. The area under the curve for the prediction of infection was
      0.72 [95% confidence interval (CI) = 0.63-0.81] for the absolute value of PCT;
      and for delta PCT:0.88 (95% CI = 0.81-0.94), P < .01. The optimal cut-off value
      was 0.79 ng/mL with the highest Youden index of 0.80 for delta-PCT to indicate
      infection. Neither absolute values nor changes in CRP, or WBC could predict
      infection better. The "delta" was considered as the changes in the absolute
      values (subtracting day t0 from day t1) of PCT, CRP, and WBC.This study suggest
      that early elevation of PCT within the first 24 hours of new onset infection,
      interpreted with clinical results, appears to be a promising indicator for the
      diagnosis of infections following LRC.

PMID- 29049198
TI  - Expression analysis of E-cad and vascular endothelial growth factor in triple
      negative breast cancer patients of different ethnic groups in western China.
AB  - The aim of this article is to investigate the expression of E-cadherin (E-cad)
      and vascular endothelial growth factor (VEGF) in triple-negative breast cancer
      (TNBC) of Han and Uygur women patients in western China, and their relationship
      with clinical features of TNBC.Totally, 172 cases of Han TNBC patients and 79
      cases of Uighur TNBC patients were enrolled. The expressions of E-cad and VEGF
      were detected with immunohistochemistry. The correlation of E-cad and VEGF
      expression with lymph node metastasis, TNM stage, and histological grade were
      analyzed. The 5-year disease-free survival rate of the 2 groups was also
      evaluated.There was no significant difference in the 5-year disease-free survival
      rate (P > .05) and the expression of E-cad between the 2 groups. The positive
      rate of VEGF in Han was significantly lower than that in Uygur (P < .05). The
      expression of E-cad was negatively correlated with lymph node metastasis, TNM
      stage, and histological grade (-1<=r < 1, P < .05). However, the expression of
      VEGF was positively correlated with lymph node metastasis and TNM staging (0 < r
      < 1, P < 0.05), but not with histological grading.The expression of E-cad and
      VEGF and their relationship with clinical features of TNBC suggest that Uygur
      TNBC patients might have different prognostic factors as compared with Han
      patients.

PMID- 29049199
TI  - Paclitaxel as third-line chemotherapy for small cell lung cancer failing both
      etoposide- and camptothecin-based chemotherapy.
AB  - Paclitaxel has been shown to have clinical activity in the treatment of small
      cell lung cancer (SCLC). However, its role as third-line chemotherapy for SCLC
      after both etoposide- and camptothecin-based regimens has not been clarified.All
      patients with refractory SCLC who were treated with paclitaxel-based regimen as
      third-line chemotherapy between 2005 and 2011 in Seoul National University
      Bundang Hospital were reviewed retrospectively. Forty patients previously treated
      with both etoposide- and camptothecin-based chemotherapy were included.The median
      age of the enrolled patients was 67 years (range, 35-86 years). Most patients
      (77.5%) received cisplatin plus etoposide as first-line therapy, and
      camptothecins such as irinotecan or topotecan as second-line therapy. Of 34
      patients with measurable lesions, 8 patients (23.5%) achieved partial response
      and 9 (26.5%) had stable disease. The median progression-free survival (PFS) and
      overall survival (OS) were 2.5 and 5.9 months, respectively. Predictive factors
      for OS were performance status (PS) (PS <2 vs >=2; P = .001), the presence of
      liver metastasis (P < .001), and number of metastatic sites (<3 vs >=3; P = .047)
      in univariate analysis. PS and liver metastasis also remained statistically
      significant in multivariate analysis. Grade 3 or 4 hematologic toxicity was 20%
      for neutropenia, and 10% for thrombocytopenia. Other common non-hematological
      toxicities were peripheral neuropathy and mild liver enzyme elevation.Paclitaxel
      based chemotherapy showed modest activity in SCLC patients refractory to both
      etoposide- and camptothecin-based chemotherapy. PS and presence of liver
      metastasis were predictive of survival after paclitaxel chemotherapy.

PMID- 29049201
TI  - Association between folate intake and risk of head and neck squamous cell
      carcinoma: An overall and dose-response PRISMA meta-analysis.
AB  - The results of published studies about the relationships between folate intake
      and risk of head and neck squamous cell carcinoma (HNSCC) remained inconsistent.
      Hence, a comprehensive and dose-response meta-analysis was performed to clarify
      the association between folate intake and HNSCC risk.The electric searches of
      Pubmed, Medline, and EMBASE databases were performed to identify the studies
      examining the relationship between folate intake and HNSCC risk on April 5, 2017.
      According to the inclusion criteria, finally 9 studies were included in this meta
      analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were
      used to evaluate the strength of associations. Dose-response analysis was
      conducted to quantitate the relationship between dietary folate intake and HNSCC
      risk.The pooled OR for assessing the risk of HNSCC and folate intake in the
      highest level versus lowest level was 0.505 (95% CI 0.387-0.623). The linearity
      model of dose-response analysis indicated that with increased 100 MUg/d folate
      intake, the risk of HNSCC decreased 4.3% degree (OR 0.957, 95% CI 0.935
      0.980).These results indicate that folate is a protective nutrient against HNSCC
      carcinogenesis.

PMID- 29049202
TI  - Mandibular Gorham-Stout disease: A case report and literature review.
AB  - RATIONALE: Gorham-Stout disease (GSD) is characterized by aggressive bone
      resorption, proliferation of vascular or lymphatic vessels, and soft-tissue
      swelling. Bones that initially appear normal start to resorb, partially or
      completely. However, the etiology of GSD is unknown. PATIENT CONCERNS: A 29-year
      old man with a chief complaint of toothache and mobility in the lower right
      mandible for the previous 1 year. DIAGNOSES: Gorham-Stout disease (GSD).
      INTERVENTIONS: The RANK-ligand inhibitor denosumab was suggested to use to
      inhibit the development of osteoclasts and slow mandibular resorption. In
      addition, we proposed resection of the remaining mandible and reconstruction via
      vascularized bone graft, after resorption of the mandible had become stationary.
      OUTCOMES: Regular follow-ups were advised to this patient to monitor the
      stability of bone resorption prior to any surgical intervention. LESSONS: We
      strongly recommend that every attempt should be made for early diagnosis and
      prompt effective medical and surgical management. The failure to do so results in
      further complications and poor prognosis.

PMID- 29049200
TI  - Subclinical atherosclerosis and history of cardiovascular events in Italian
      patients with rheumatoid arthritis: Results from a cross-sectional, multicenter
      GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study.
AB  - Several studies have pointed out a significant association between rheumatoid
      arthritis (RA) and accelerated atherosclerosis. At the best of our knowledge, no
      such study has been carried out in a large Italian series and, in this study, we
      aimed to investigate the prevalence of both subclinical atherosclerosis and
      history of cardiovascular events (CVEs), in patients consecutively admitted from
      January 1, 2015 to December 31, 2015 to Rheumatology Units throughout the whole
      Italy.Centers members of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia
      Clinica e Sperimentale) were invited to enrol patients consecutively admitted
      from January 1, 2015 to December 31, 2015 and satisfying American College of
      Rheumatology/ European League Against Rheumatism criteria for RA and to
      investigate each of them for: traditional cardiovascular risk factors: sex, age,
      smoking habit, total cholesterol, triglycerides, glycaemia, high blood pressure,
      metabolic syndrome (MS), type 2 diabetes (T2D); RA features: disease duration as
      assessed from the first symptom, disease activity as evaluated by DAS28,
      radiographic damage as assessed by hands and feet x-ray, and previous joint
      surgery; prevalence of both subclinical atherosclerosis and history of CVEs.Eight
      centers participated to the study. From January 1, 2015 to December 31, 2015, the
      1176 patients, who had been investigated for all the items, were enrolled in the
      study. They were mostly women (80.52%), with a median age of 60 years (range, 18
      91 years), a median disease duration of 12 years (range, 0.8-25 years),
      seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low
      disease activity; 39.45% moderate disease activity; 22.61% high disease
      activity.Eighty-two patients (6.9%) had a history for CVEs (58 myocardial
      infarction, 38 heart failure, 10 ischemic transitory attack, and 7 stroke). This
      figure appears to be lower than that reported worldwide (8.5%). After excluding
      the 82 patients with a history of CV events, subclinical atherosclerosis was
      detected in 16% of our patients, (176 patients), a figure lower than that
      reported worldwide (32.7%) and in previous Italian studies.This is the first
      Italian multicenter study on subclinical and clinical atherosclerosis in patients
      with RA. We pointed out a low prevalence of both subclinical atherosclerosis and
      history of CV events.

PMID- 29049203
TI  - Standing beat-to-beat blood pressure variability is reduced among fallers in the
      Malaysian Elders Longitudinal Study.
AB  - The aim of this study was to determine the relationship between falls and beat-to
      beat blood pressure (BP) variability.Continuous noninvasive BP measurement is as
      accurate as invasive techniques. We evaluated beat-to-beat supine and standing BP
      variability (BPV) using time and frequency domain analysis from noninvasive
      continuous BP recordings.A total of 1218 older adults were selected. Continuous
      BP recordings obtained were analyzed to determine standard deviation (SD) and
      root mean square of real variability (RMSRV) for time domain BPV and fast-Fourier
      transform low frequency (LF), high frequency (HF), total power spectral density
      (PSD), and LF:HF ratio for frequency domain BPV.Comparisons were performed
      between 256 (21%) individuals with at least 1 fall in the past 12 months and
      nonfallers. Fallers were significantly older (P = .007), more likely to be female
      (P = .006), and required a longer time to complete the Timed-Up and Go test (TUG)
      and frailty walk test (P <= .001). Standing systolic BPV (SBPV) was significantly
      lower in fallers compared to nonfallers (SBPV-SD, P = .016; SBPV-RMSRV, P = .033;
      SBPV-LF, P = .003; SBPV-total PSD, P = .012). Nonfallers had significantly higher
      supine to standing ratio (SSR) for SBPV-SD, SBPV-RMSRV, and SBPV-total PSD (P =
      .017, P = .013, and P = .009). In multivariate analyses, standing BPV remained
      significantly lower in fallers compared to nonfallers after adjustment for age,
      sex, diabetes, frailty walk, and supine systolic BP. The reduction in frequency
      domain SSR among fallers was attenuated by supine systolic BP, TUG, and frailty
      walk.In conclusion, reduced beat-to-beat BPV while standing is independently
      associated with increased risk of falls. Changes between supine and standing BPV
      are confounded by supine BP and walking speed.

PMID- 29049204
TI  - The genetic association between PON1 polymorphisms and osteonecrosis of femoral
      head: A case-control study.
AB  - The purpose of this study was to investigate the relationship between Paraoxonase
      1 (PON1) gene rs662, rs854555 polymorphisms and osteonecrosis of the femoral head
      (ONFH) in Han population, northern China.Polymerase chain reaction-restriction
      fragment length polymorphism was used to determine genotypes of PON1
      polymorphisms in 84 patients with ONFH and 96 healthy persons. chi test was used
      to compare distribution differences of genotype, allele, and haplotype between
      the case and control groups. The odds ratio (OR) and 95% confidence interval (CI)
      were calculated to reveal the effects of PON1 polymorphisms on risk of ONFH, and
      the results were adjusted using logistic regression analysis. The linkage
      disequilibrium and haplotype analysis were performed with haploview software.That
      people carrying AA genotype of rs662 were easier to be attacked by ONFH than GG
      genotype carriers (OR = 2.53, 95% CI = 1.05-6.07, P = .038). Meanwhile, the
      frequency of A allele in the case group was significantly higher than the
      controls and it was a risk factor for ONFH (OR = 1.56, 95% CI = 1.03-2.38, P =
      .038). The A-A haplotype frequency of rs854555-rs662 in PON1 was significantly
      correlated to the increased susceptibility to ONFH (OR = 2.74, 95% CI = 1.28
      5.84).The rs662 polymorphism in PON1 may be associated with ONFH susceptibility,
      but not rs854555 in Han population, northern China. Additionally, haplotype is
      also a nonignorable risk factor.

PMID- 29049205
TI  - Using a novel T-lymph node ratio model to evaluate the prognosis of nonmetastatic
      breast cancer patients who received preoperative radiotherapy followed by
      mastectomy: An observational study.
AB  - We aimed to investigate the prognostic value of postpathological characters in
      nonmetastatic breast cancer (NMBC) patients who received preoperative
      radiotherapy (PRT) followed by mastectomy (MAST).We conducted retrospective
      analyses using the data collected from the Surveillance, Epidemiology, and End
      Results program of the National Cancer Institute. Univariate and multivariate
      analyses were performed to identify prognostic factors. Disease-specific survival
      was calculated by the Kaplan-Meier curve and validated by log rank test. The
      discriminations of independent risk factors and staging systems were compared by
      the area under receiver operating characteristic curves (AUC) and validated by
      Harrell concordance index (bootstrapping algorithm). Akaike information criterion
      (AIC) was applied to compare the difference of model.One thousand three hundred
      fifty NMBC patients who had received PRT followed by MAST from 1988 to 2013 were
      included in the study. We found the metastatic lymph node ratio (mLNR) staging
      was a superior indicator than pN staging. Thus, we proposed a T-lymph node ratio
      (T-NR) staging system with simplified-T categories (T0-3 and T4) and the mLNR
      staging. The novel T-NR staging system provided larger AUC (P = .024, .008,
      respectively) and the smaller AIC (P < .001) value than American Joint Committee
      on Cancer staging system.The novel T-NR staging system performed more accurate
      survival prediction and better model fitness for NMBC patients who receive PRT
      followed by MAST, it may provide a wide applicability in clinical decision
      making.

PMID- 29049206
TI  - The molecular epidemiology of respiratory viruses associated with asthma attacks:
      A single-center observational study in Japan.
AB  - Few reports have described the significance of viral respiratory infections
      (VRIs) in exacerbation of asthma in adult patients. The aim of this study was to
      elucidate the profiles of VRIs in adult patients with asthma along with their
      molecular epidemiology.A cross-sectional observational study was conducted at
      Kyorin University Hospital from August 2012 to May 2015. To identify respiratory
      pathogens in inpatients and outpatients suffering from asthma attacks, RT
      PCR/sequencing/phylogenetic analysis methods were applied alongside conventional
      microbiological methods. Phylogenetic and pairwise distance analyses of 10
      viruses were performed.A total of 106 asthma attack patients enrolled in this
      study in both inpatient (n = 49) and outpatient (n = 57) settings. The total 106
      respiratory samples were obtained from nasopharyngeal swab (n = 68) or sputum (n
      = 38). Among these, patients with virus alone (n = 39), virus and bacterial (n =
      5), and bacterial alone (n = 5) were identified. The ratio of virus-positive
      patients in inpatient or outpatient to the total cases were 31.1% (n = 33) and
      10.4% (n = 11), respectively. The frequency of virus-positive patients was
      significantly higher in inpatients (75.3%, n = 33) than in outpatients (19.3%, n
      = 11). Major VRIs included human rhinovirus (HRV) (n = 24), human metapneumovirus
      (hMPV) (n = 9), influenza virus (Inf-V) (n = 8), and respiratory syncytial virus
      (RSV) (n = 3) infections with seasonal variations. HRV-A and HRV-C were the most
      commonly detected viruses, with wide genetic divergence on phylogenetic
      analysis.Asthmatic exacerbations in adults are highly associated with VRIs such
      as HRV-A or HRV-C, hMPV, RSV, and Inf-V infections with seasonal variations and
      genetic divergence, but similar frequencies of VRIs occurred in asthma attack
      patients throughout the seasons.

PMID- 29049207
TI  - Cutaneous mucormycosis in a patient with lupus nephritis: A case report and
      review of literature.
AB  - RATIONALE: Mucormycosis is a rare fungal infection but life-threatening,
      especially in lupus nephritis (LN). Mucormycosis may manifest as rhino-orbital
      cerebral, pulmonary, cutaneous, gastrointestinal, renal, or disseminated forms.
      PATIENT CONCERNS: We report a case of a 52-year-old woman with cutaneous
      mucormycosis infection who was admitted because of LN. DIAGNOSES:
      Histopathological analysis of the lesion confirmed the Rhizopus microspores from
      the family Mucoraceae. INTERVENTIONS AND OUTCOMES: The mortality of mucormycosis
      remains unacceptably high. Our patient died at last even with standard therapy
      (aggressive surgical debridement and anti-mucormycosis drugs). LESSONS: It is
      difficult to diagnose because lacking of specific clinical features, it is
      necessary to identify the susceptible patients, and then make diagnosis rapidly
      through tissue biopsy. Despite the outcome is poor, aggressive surgical
      debridement and Amphotericin B/Posaconazole can be effective.

PMID- 29049208
TI  - Association between the polymorphisms in XPG gene and gastric cancer
      susceptibility in Chinese populations: A PRISMA-compliant meta-analysis.
AB  - BACKGROUND: Several previous studies were carried out on the association between
      xeroderma pigmentosum group G (XPG) gene polymorphisms (including rs873601 G>A,
      rs2094258 C>T, rs2296147 T>C, and rs751402 C>T) and the risk of gastric cancer in
      Chinese populations. However, their conclusions were not consistent. Therefore,
      this meta-analysis was performed by us to investigate the association between the
      4 potentially functional single nucleotide polymorphisms (SNPs) of XPG gene and
      gastric cancer risk. METHODS: The eligible literatures were identified through
      PubMed, Embase, Ovid MEDLINE, Web of Science, CNKI, and Wan fang databases up to
      July 2017. Finally, 5 studies for rs873601, 7 studies for rs2094258, 4 studies
      for rs2296147, and 8 studies for rs751402 were used for the current meta
      analysis. RESULTS: Of the 4 included SNPs, only rs751402 was showed to be
      associated with the risk of gastric cancer [C vs T, odds ratio (OR) = 1.16, 95%
      confidence interval (CI) = 1.04-1.29; CC + CT vs TT, OR = 1.23, 95% CI = 1.00
      1.52; CC vs CT + TT, OR = 1.15, 95% CI = 1.05-1.27; CC vs TT, OR = 1.35, 95% CI =
      1.06-1.72; CC vs CT, OR = 1.13, 95% CI = 1.02-1.25]. CONCLUSION: The current meta
      analysis demonstrated that the XPG gene polymorphism rs751402 was associated with
      increased susceptibility to gastric cancer in Chinese populations. However,
      studies with a larger number of subjects among different ethnic groups are needed
      to further validate the results.

PMID- 29049209
TI  - Pravastatin for prevention of HELLP syndrome: A case report.
AB  - RATIONALE: Pravastatin has emerged for prevention and treatment of preeclampsia;
      no reports are available on pravastatin and HELLP (hemolysis, elevated liver
      enzymes and low platelets) syndrome. PATIENT CONCERNS: The first pregnancy
      necessitated termination of pregnancy at gestational age (GA) 20+5 for HELLP.
      Intrauterine fetal death at GA 22+5 occurred in the second pregnancy, whilst on
      temporizing management of HELLP. DIAGNOSES: Severe, recurrent early-onset HELLP
      syndrome. INTERVENTIONS: In her fourth pregnancy, pravastatin was commenced at GA
      13. OUTCOMES: The course of pregnancy was uncomplicated, and a healthy,
      appropriate for gestational age fetus was delivered at term. LESSONS: Pravastatin
      may be effective in prevention of HELLP. The hepatic uptake may be of particular
      advantage.

PMID- 29049210
TI  - Topical use of tranexamic acid can effectively decrease hidden blood loss during
      posterior lumbar spinal fusion surgery: A retrospective study.
AB  - In spinal fusion surgery, total blood loss (TBL) is composed of visible blood
      loss from the surgical field and wound drainage, and hidden blood loss (HBL).
      Until now, no published studies exist reporting the effect of topical use of
      tranexamic acid (tTXA) on HBL in patients undergoing posterior lumbar spinal
      fusion surgery. This study aimed to explore the effect of tTXA on HBL during
      primary posterior lumbar spinal fusion surgery. Between September 2014 and
      September 2016, 100 adult patients (age > 18 years) with lumbar disc herniation
      or lumbar spinal stenosis undergoing primary posterior lumbar instrumented spinal
      fusions at 1 institution were divided into tTXA and control groups. The primary
      outcome was HBL. Secondary outcomes include TBL, intraoperative blood loss (IBL),
      postoperative blood loss (PBL), hemoglobin (HGB) levels on preoperative (Pre-op)
      and postoperatively (days 1-3, POD1, POD2, POD3, respectively), and amount of
      allogeneic blood transfusion. Complications occurring perioperatively until
      hospitalization discharge were also collected. In the tTXA group (n = 50
      patients), wound surface was soaked with TXA (1 g in 100 mL saline solution) for
      5 minutes before wound closure. For the control group (n = 50 patients), wound
      surface was soaked with the same volume of normal saline. There were no
      significant differences in demographics, surgical traits between the 2 groups.
      There were no significant differences in IBL or perioperative blood transfusion
      requirements between the 2 groups. However, in the tTXA group, TBL, PBL, and HBL
      were significantly lower than those in the control group (550 +/- 268 vs 833 +/-
      298 mL, 53.5 +/- 43.9 vs 136.7 +/- 87.9 mL, 356.7 +/- 254.8 vs 501.1 +/- 216.9
      mL, P < .001, respectively). HGB levels were significantly higher in the tTXA
      group (P < .001) on POD1 and had a slower decline on POD2 and POD3 than the
      control group. No complications associated with TXA were observed. From these
      data, we conclude that tTXA can effectively reduce HBL, without significant
      complications in adult patients undergoing posterior lumbar spinal fusion
      surgery.

PMID- 29049211
TI  - The efficacy and safety of early initiation of preoperative analgesia with
      celecoxib in patients underwent arthroscopic knee surgery: A randomized,
      controlled study.
AB  - This study aimed to investigate the efficacy and safety of celecoxib 24 hours
      preoperative, 1 hour preoperative, and 4 hours postoperative administration in
      patients with arthroscopic knee surgery (AKS).In all, 206 patients who underwent
      AKS were consecutively recruited and randomized into 3 groups: (1) early
      preoperative analgesia group (EPEA), celecoxib 400 mg 24 hours preoperative
      administration; (2) preoperative analgesia group (PEA), celecoxib 400 mg 1 hour
      preoperative administration; (3) postoperative analgesia group (POA), celecoxib
      400 mg 4 hours postoperative administration. Pain visual analog scale (VAS)
      scores (at rest and at 90 flexion) and patient global assessment (PGA) score were
      evaluated before and after operation, and also pethidine consumption and adverse
      events (AEs).The pain-rest VAS score, percentage of patients with moderate-severe
      pain at rest, and PGA score in the EPEA and PEA groups were decreased compared
      with POA group at 8 and 12 hours postoperation. Besides, pain-flexion to 90 VAS
      score in EPEA and PEA groups were also reduced compared with POA group at 8 hours
      postsurgery. Interestingly, the percentage of patients with moderate-severe pain
      at 90 flexion at 8 hours postsurgery in PEA group was fewer compared with POA
      group, whereas at 4 hours postoperation it was reduced in EPEA group compared
      with PEA and POA groups. As to consumption of pethidine, it was numerically
      decreased in EPEA and PEA groups compared with POA group. No difference between
      each 2 groups was found in AEs.Celecoxib was effective and safe as pre-emptive
      analgesia in AKS, and 1 hour administration before operation might be an optimal
      choice.

PMID- 29049212
TI  - Comparison of oncological outcomes of right-sided colon cancer versus left-sided
      colon cancer after curative resection: Which side is better outcome?
AB  - PROPOSE: There are embryological origins, anatomical, histological, genetic, and
      immunological differences between right-sided colon cancer (RCC) and left-sided
      colon cancer (LCC). Many studies have sought to determine the survival and
      prognosis according to tumor location. This study aimed to analyze outcomes
      between RCC and LCC. MATERIAL AND METHOD: Between January 2000 and December 2012,
      data on 414 patients who underwent curative resection for RCC and LCC were
      retrieved from a retrospective database. Propensity score matching (1:1) was
      performed and RCC was identified in 207 and LCC in 207 patients. RESULTS: On
      average, RCC exhibited a more advanced N stage, increased tumor size, more
      frequently poorly differentiated tumors, more harvested lymph nodes, and more
      positivity of lymphovascular invasion than LCC. With a median follow-up of 66.7
      months, the 5-year overall survival (OS) rates for RCC and LCC were 82.1% and
      88.7%, respectively, (P < .05). The 5-year disease-free survival (DFS) rates were
      81.4% (RCC) and 88.3% (LCC; P < .05). In stage III cancers, the DFS rates were
      61.1% (RCC) and 81.9% (LCC; P < .05), while the OS rates were 65.6% (RCC) and
      78.6% (LCC; P = .056). CONCLUSION: On the basis of present data, LCC exhibited
      better survival outcomes than RCC after curative resection. Especially in stage
      III, LCC showed better oncologic outcomes. Proper specialized treatment related
      to the location of colon cancer is needed.

PMID- 29049213
TI  - Clinical characteristics and prognostic risk factors of healthcare-associated
      pneumonia in a Korean tertiary teaching hospital.
AB  - The 2016 American Thoracic Society and Infectious Diseases Society of America
      (ATS/IDSA) guidelines removed the concept of healthcare-associated pneumonia
      (HCAP). We examined whether the 2016 ATS/IDSA guidelines are applicable in
      Korea.We conducted a retrospective, observational study of pneumonia patients who
      were hospitalized at a tertiary teaching hospital from March 2012 to February
      2014. Identified pathogens that were not susceptible to beta-lactams, macrolides,
      and fluoroquinolones were defined as community-acquired pneumonia drug-resistant
      pathogens (CAP-DRPs). We analyzed the risk factors for 28-day mortality and the
      occurrence rate of CAP-DRPs.Of the 1046 patients, 399 were classified with HCAP
      and 647 with CAP. HCAP patients were older and had more comorbidities than CAP
      patients. Initial pneumonia severity index (PSI) was higher in patients with HCAP
      than with CAP. HCAP was associated with not only an increased rate of CAP-DRPs
      (HCAP, 19.8%; CAP, 4.0%; P < .001) but also an increased rate of inappropriate
      initial antibiotic therapy (IIAT) (HCAP, 16.8%; CAP, 4.6%; P < .001). HCAP was
      also associated with an increased 28-day mortality rate compared with CAP (HCAP,
      14.5%; CAP, 6.3%; P < .001). In a multivariable analysis, PSI was an independent
      risk factor for 28-day mortality in HCAP patients (odds ratio 1.02, 95%
      confidence interval 1.01-1.04). CAP-DRPs and IIAT were not associated with
      mortality.Patients with HCAP revealed higher rates of CAP-DRPs, IIAT, and
      mortality than patients with CAP. However, CAP-DRPs and IIAT were not associated
      with mortality. PSI was the main predictive factor for 28-day mortality in
      patients with HCAP.

PMID- 29049214
TI  - Complete transmural migration of a retained surgical sponge: an atypical case in
      image mimicking intussusception: A case report.
AB  - RATIONALE: Intraluminal migration of a retained surgical sponge causing
      intestinal obstruction and fistula is extremely rare occurrence. PATIENT
      CONCERNS: A case of a 35-year-old male, who complaining a diffuse abdominal pain
      beginning three days earlier. He also complained of occasional vomiting,
      nonspecific abdominal pain, and an unintentional 15 kg weight loss during the
      past 2 years. However, there were no clear findings in previous laboratory work.
      He had received an open appendectomy approximately 4 years earlier. DIAGNOSES:
      Retained surgical sponge. INTERVENTIONS: A contrast-enhanced CT of the abdomen
      showed a clear invagination of the small intestine. However, intraoperatively, we
      could not find an intestinal segment with intussusception. After the adhesive
      intestine was detached, a jejunal-ileal cross-linked fistula was found. More
      surprisingly, a retained surgical sponge was found inside the ileal fistula when
      the cross-linked fistula was detached. OUTCOMES: The patient was discharged 7
      days after surgery. LESSONS: This is the first report showing an atypical image
      of a complete transmural migration of a retained surgical sponge mimicking
      intussusception.

PMID- 29049215
TI  - Pain intensity and abdominal muscle activation during walking in patients with
      low back pain: The STROBE study.
AB  - Nonspecific low back pain (LBP) is a common musculoskeletal problem that is
      intensified during physical activity. Patients with LBP have been reported to
      change their abdominal muscle activity during walking; however, the effects of
      pain intensity, disability level, and fear-avoidance belief on this relationship
      have not been evaluated. Thus, we compared abdominal muscle activity in patients
      with LBP and asymptomatic controls, and assessed the impact of pain intensity,
      disability level, and fear-avoidance belief.Thirty patients with LBP divided into
      groups reporting low (LLBP) and high-pain intensity low back pain (HLBP), and 15
      participants without LBP were recruited. LBP patients' self-reported pain
      intensity, disability, and fear-avoidance belief were recorded. To examine
      abdominal muscle activity (rectus abdominis [RA], internal [IO], and external
      oblique [EO] muscles) during walking, all subjects walked at a self-selected
      speed. Abdominal muscle activity (RA, IO, and EO) was compared among groups
      (LLBP, HLBP, and controls) in different phases of walking (double support vs
      swing). Relationships between abdominal muscle activity and clinical measures
      (pain intensity, disability, fear-avoidance belief) were analyzed using partial
      correlation analysis.Right IO muscle activity during walking was significantly
      decreased in LLBP and HLBP compared with controls in certain walking phase.
      Partial correlation coefficients showed significant correlations between fear
      avoidance belief and right EO activity (r = .377, P < .05) and between disability
      index and left IO activity (r = .377, P < .05) in patients with LBP. No
      significant difference was found in abdominal muscle activity in walking between
      patients with LLBP and HLBP (P > .05).This study demonstrated decreased IO muscle
      activity during certain walking phases in LLBP and HLBP compared with
      asymptomatic participants. Although altered IO muscle activity during walking was
      observed in patients with LBP, no changes were found with other abdominal muscles
      (EO, RA). Thus, these results provide useful information about abdominal muscle
      activity during walking in patients with LBP.

PMID- 29049216
TI  - Fondaparinux is effective for acute portal vein thrombosis in decompensated
      cirrhotic patients.
AB  - Portal vein thrombosis (PVT) is a rare but serious complication in the
      decompensated stage of cirrhosis, and recurrent upper gastrointestinal bleeding
      and refractory ascites can occur in such patients. In decompensated cirrhotic
      patients, the application of conventional anticoagulant therapy is limited due to
      severe coagulation disorders, thrombocytopenia, and history of gastrointestinal
      bleeding.In this study, we sought to investigate the effect of fondaparinux on
      acute PVT in decompensated cirrhotic patients.Patients were treated with
      fondaparinux (2.5 mg, q 24 h, subcutaneously) in the region of the umbilicus for
      conventional liver protection, after a clear diagnosis was made and
      contraindications such as active bleeding were ruled out. Other anticoagulants
      and circulation-improving drugs were not administered. Platelet count,
      prothrombin time, international normalized ratio, D dimer (DD), and liver
      function were measured. Furthermore, portal vein color Doppler ultrasound was
      performed every 7 days while patients were treated with fondaparinux and after
      portal vein recanalization.The portal vein was recanalized in all patients after
      treatment (P = .018). The decline in DD had a predictive value for portal vein
      recanalization (P = .018). No side effects such as bleeding or thrombocytopenia
      occurred in any of the patients (P > .05).Selective factor Xa inhibitor
      fondaparinux is effective and safe for acute PVT in decompensated cirrhotic
      patients.

PMID- 29049217
TI  - Identification of novel therapeutic target genes and pathway in pancreatic cancer
      by integrative analysis.
AB  - BACKGROUND: Gene alterations are crucial to the molecular pathogenesis of
      pancreatic cancer. The present study was designed to identify the potential
      candidate genes in the pancreatic carcinogenesis. METHODS: Gene Expression
      Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and
      the differentially expressed genes (DEGs) from individual microarray data were
      merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks, and
      gene coexpression analysis were performed. RESULTS: Three GEO datasets, including
      74 pancreatic cancer samples and 55 controls samples were selected. A total of
      2325 DEGs were identified, including 1383 upregulated and 942 downregulated
      genes. The GO terms for molecular functions, biological processes, and cellular
      component were protein binding, small molecule metabolic process, and integral to
      membrane, respectively. The most significant pathway in KEGG analysis was
      metabolic pathways. PPI network analysis indicated that the significant hub genes
      including cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1), mitogen
      activated protein kinase 3 (MAPK3), and phospholipase C, gamma 1 (PLCG1). Gene
      coexpression network analysis identified 4 major modules, and the potassium
      channel tetramerization domain containing 10 (KCTD10), kin of IRRE like (KIRREL),
      dipeptidyl-peptidase 10 (DPP10), and unc-80 homolog (UNC80) were the hub gene of
      each modules, respectively. CONCLUSION: Our integrative analysis provides a
      comprehensive view of gene expression patterns associated with the pancreatic
      carcinogenesis.

PMID- 29049218
TI  - Cardiovascular findings on computed tomography in patients with unclear finding
      situation and trauma of unknown origin.
AB  - Incidental cardiovascular findings are common and can be found in up to 70% of
      patients. Previously, several reports about incidental findings (IFs) on whole
      body computed tomography (CT) were published. However, no previous study
      investigated cardiovascular IFs in patients with unclear finding situation and
      trauma of unknown origin on whole body CT.The radiological database of 2
      university hospitals was screened for patients with trauma of unknown origin and
      unclear finding situation investigated by whole body CT. The images were
      retrospectively analyzed by 2 radiologists in consensus. The findings were
      classified according to their clinical relevance. Clinically nonrelevant findings
      like valvular sclerosis, aortic sclerosis, or anatomic variants were excluded
      from this study. Moreover, the radiology reports were analyzed to assess initial
      reporting by the radiologist.Overall, we identified 60 patients with a mean age
      of 63 years. A total of 98 clinically relevant cardiovascular IFs (CRCIF) were
      identified in 60 (75%) patients (1.6 CRCIF per patient). The most prevalent
      finding was cardiomegaly in 23 patients, followed by coronary sclerosis in 21
      patients and aortic ectasia in 11 patients; other findings were rarer. Sixty-one
      findings were reported (62.2%) and 37 were nonreported (37.8%). Thirty patients
      (50%) showed no traumatic event on whole body CT.CRCIFs are common in patients
      with unclear finding situation and trauma of unknown origin. Despite initial
      indication for trauma detection, the whole body CT should carefully be evaluated
      for CRCIF because of the high prevalence of clinically relevant findings.
      Notably, 37.76% of the findings were not reported by the radiologist.

PMID- 29049219
TI  - Risk assessment of morbidly obese parturient in cesarean section delivery: A
      prospective, cohort, single-center study.
AB  - BACKGROUND: Up to 40% of women gain excessive weight during pregnancy. Obesity
      complications and risks in parturient women undergoing cesarean section (CS) with
      different anesthetic methods remain unknown. This study aimed to assess the
      safety and risk of obese women undergoing CS delivery with various perioperative
      anesthetic methods. METHODS: Seven hundred ninety parturient women underwent CS
      under general anesthesia (GA), intraspinal anesthesia including epidural
      anesthesia (EA) and combined spinal-epidural anesthesia (CSEA). They were divided
      into morbid (n = 255), severe (n = 274), and non-obesity (n = 261) groups. This
      study is registered with ClinicalTrials.gov (number NCT03002636). RESULT: Between
      2013 and 2016, 790 pregnant were assessed. Compared with the non-obesity group,
      there were significantly more fetal distress and higher body mass index (BMI) in
      the morbid obesity group (P = .0001 and P = .001, respectively). Significantly
      more patients showed preeclampsia, multifetation, amniotic fluid abnormality, and
      high bleeding amounts in the morbid obesity group compared with the non-obesity
      group (P = .0001, P = .048, P = .017, and P = .018, respectively); more patients
      were administered EA and GA compared with the non-obesity group (P = .0001 and P
      = .0001, respectively). More post-anesthesia care unit (PACU) patients were found
      in the severe obesity group no more than the non-obesity group. Significantly
      increased anesthesia puncture times for 5 > n >= 3 and n >= 5 were obtained in
      the morbid obesity group (P = .0001 and P = .0001, respectively), with more
      patients in the puncture sitting position, compared with the non-obesity group (P
      = .0001). CONCLUSION: GA, EA, and CSEA are safe and effective in severely or
      morbidly obese patients. Morbidly obese parturient show increased likelihood for
      fetal distress, PACU, sitting position puncture, puncture difficulty, and other
      pregnancy complications. There were more anesthesia puncture times in morbidly
      obese patients.

PMID- 29049221
TI  - Percutaneous microwave ablation liver partition and portal vein embolization for
      planned hepatectomy due to large gastrointestinal stromal tumor metastases: A
      case report.
AB  - RATIONALE: The liver is the most frequent site of relapse of gastrointestinal
      stromal tumors (GISTs). Surgery is always considered to be unsuitable because of
      the multiple metastases. PATIENT CONCERNS: In this report, we describe a case of
      large, multiple GIST liver metastases that were treated with percutaneous
      microwave ablation liver partition and portal vein embolization for planned
      hepatectomy (PALPP). A 44-year-old woman had undergone pancreaticoduodenectomy 4
      years previously because of the diagnosis of a large duodenal GIST. Large,
      multiple liver metastases were observed 2 years later. DIAGNOSES: GIST liver
      metastasis was diagnosed using percutaneous ultrasound-guided biopsy.
      INTERVENTIONS: After 6 months of treatment with imatinib, the liver metastasis
      was stable. PALPP was performed because of insufficient future liver remnant
      (FLR) and right trisegmentectomy was successfully completed 10 days later.
      OUTCOMES: The patient has had no signs of local or systemic disease during 17
      months of postsurgical follow-up. LESSONS: PALPP provides a new methodology for
      treatment of GIST liver metastasis in patients with insufficient FLR, and may
      have benefit in prolonging a durable remission.

PMID- 29049220
TI  - The association between CCND1 G870A polymorphism and colorectal cancer risk: A
      meta-analysis.
AB  - BACKGROUND: CyclinD1 (CCND1) is a key cell cycle regulatory protein. A large
      number of epidemiological studies have assessed the potential correlation between
      the CCND1 G870A polymorphism and the risk of colorectal cancer (CRC), but their
      findings have been inconsistent. To obtain a more precise understanding of the
      association between the G870A polymorphism in the CCND1 gene and the CRC risk, we
      conducted a more comprehensive meta-analysis. METHODOLOGY: We searched PubMed,
      Ovid, Springer, Weipu, China National Knowledge Infrastructure (CNKI), and
      Wanfang databases, covering all publications (the last search was updated on
      January 10, 2017). The pooled odds ratios (ORs) with 95% confidence intervals
      (CIs) were derived from a fixed effect or random effect model. Statistical
      analyses were performed using Review Manager 5.3 and STATA 10.0 software.
      RESULTS: A total of 7276 CRC patients and 9667 controls from 27 publications were
      included in this meta-analysis. We found that compared with GG homozygote genetic
      model, AA, AG, AA + AG genetic models of the CCND1 G870A polymorphism were
      significantly associated with overall CRC risk (AA homozygote genetic model: OR =
      1.28, 95% CI = 1.10-1.49; AG heterozygote genetic model: OR = 1.15, 95% CI = 1.06
      1.25; AA homozygote + AG heterozygote genetic model: OR = 1.19, 95% CI = 1.07
      1.33). Subgroup analyses by ethnicity and cancer location showed that A carriers
      were consistently associated with a significantly increased risk of CRC in all
      subsets of participants (Asian and Caucasian; colon cancer and rectal cancer).
      When stratified by study design, we found a significant association in hospital
      based studies (HB), but no significant associations were found in either
      population-based studies (PB) or family-based studies (FB). According to subgroup
      analysis by cancer type, the risk of sporadic colorectal cancer (sCRC) and
      hereditary nonpolyposis colorectal cancer (HNPCC) were not correlated with the
      CCND1 G870A polymorphism, except AG (AG vs GG: OR = 1.30, 95% CI = 1.11-1.53).
      CONCLUSIONS: This meta-analysis suggests that the CCND1 G870A polymorphism is
      associated with an increased risk of CRC, especially that A carriers may be a
      major risk factor for CRC.

PMID- 29049222
TI  - Lower blood pressure and smaller pulse pressure in sleeping pill users: A large
      scale cross-sectional analysis.
AB  - This study aimed to investigate the association between sleeping pill use and
      hypertension or blood pressure (BP) via a cross-sectional analysis.A total of
      11,225 subjects (5875 men and 5350 women) underwent health examinations. We
      compared the proportion of sleeping pill users among hypertension (n = 5099) and
      normotensive (n = 6126) participants. We analyzed participants with no intake of
      antihypertensive medication (n = 7788), comparing the proportions with high
      systolic BP (SBP) >=140, high diastolic BP (DBP) >=90, and high pulse pressure
      (PP) >=50 mm Hg across 3 subgroups. These groups were classified according to the
      sleeping pill use [nonuse group (n = 6869); low-frequency-use group, defined as
      taking sleeping pills <=2 days per week (n = 344); and high-frequency-use group,
      defined as taking sleeping pills >=3 days per week (n = 575)].In the
      multivariable-adjusted model, odds of sleeping pill use (odds ratio (OR), 1.14; P
      < .05) was significantly higher in the hypertensive group compared with the
      normotensive group. In participants with no intake of antihypertensive
      medication, odds of high SBP (OR, 0.65; P < .0005), high DBP (OR, 0.58; P <
      .005), and high PP (OR, 0.77; P < .01) were significantly lower in the high
      frequency-use group compared with the nonuse group. Odds of high DBP (OR, 0.59; P
      < .05) was significantly lower in the low-frequency-use group.Sleeping pills were
      more frequently required in hypertensive participants than in the normotensive
      ones. Sleeping pill use may decrease BP and assist in the treatment of high BP in
      patients with sleep disturbances.

PMID- 29049223
TI  - Myocardial CT perfusion imaging for pre- and postoperative evaluation of
      myocardial ischemia in a patient with myocardial bridging: A case report.
AB  - RATIONALE: Although myocardial bridging (MB) is usually considered as benign,
      initial medical therapy and following surgical treatment in drug-refractory cases
      has been widely accepted for managing symptomatic MB. Before the patient proceeds
      to percutaneous or surgical intervention, however, the presence of objective
      ischemia in the corresponding myocardial territory should be documented. PATIENT
      CONCERN AND INTERVENTION: We herein report a 43-year-old male complaining of
      chest pain in whom cardiac CT with myocardial perfusion (cCTP) showed an MB of
      left anterior descending artery (LAD) with preoperative perfusion defect in
      corresponding myocardium and normalization of perfusion after supra-arterial
      myotomy. DIAGNOSIS: Myocardial bridging-induced ischemia. LESSONS: This case
      illustrates the potential utility of cCTP for the simultaneous assessment of MB
      and its hemodynamic significance for treatment planning and post-therapeutic
      evaluation although further research is needed to establish the clinical
      usefulness of this technique.

PMID- 29049224
TI  - Primary stability in total hip replacement: A biomechanical investigation.
AB  - BACKGROUND: In total hip replacement (THR), it is essential to achieve a primary
      stability to guarantee good long-term results. A novel locking screw hip (LSH)
      stem, anchored to the medial cortex of the proximal femur by 5 monocortical
      locking screws, was developed to overcome the shortcomings of uncemented press
      fit and cemented straight stems while simultaneously achieving primary stability.
      The aim of this study was to investigate the biomechanical competence of the LSH
      stem in comparison to an uncemented press-fit stem. METHODS: Six pairs of
      embalmed human cadaveric femora from donors aged 68 to 84 years were assigned to
      2 study groups (n = 6) with equal number of right and left bones. The specimens
      in each group and pair were implanted with either an uncemented press-fit stem or
      an LSH-stem and tested biomechanically under progressively increasing cyclic
      axial loading until catastrophic failure. Axial construct stiffness, failure
      load, and cycles to failure were detected and statistically evaluated at a level
      of significance P = .05. RESULTS: Although the axial stiffness was comparable for
      both prosthesis types, the uncemented press-fit stem showed a significant lower
      stability in terms of failure load and cycles to failure in comparison to the LSH
      stem, P = .04. CONCLUSION: Converting our results to percentage of bodyweight
      (BW) in an assumed adult patient of 80 kg shows that the LSH-stem achieves a
      primary stability allowing to carry average loads of up to 507% BW, whereas the
      uncemented press-fit stem carried average loads of up to 404% BW. We conclude
      that both stems achieve a primary stability strong enough to carry hip joint
      loads experienced in the immediate rehabilitation period after THR.

PMID- 29049225
TI  - Factors related to pediatric obstructive sleep apnea-hypopnea syndrome in
      children with attention deficit hyperactivity disorder in different age groups.
AB  - This study aimed to retrospectively investigate the factors related to pediatric
      obstructive sleep apnea-hypopnea syndrome (OSAHS) with attention deficit
      hyperactivity disorder (ADHD) in children younger than 6 years and those older
      than 6 years.A total of 437 children who were hospitalized due to OSAHS between
      January 2014 and December 2014 were retrospectively reviewed. The children were
      further divided into OSAHS group and OSAHS + ADHD group. The general
      characteristics, OSA-18 quality of life, intention-hyperactivity score, and
      polysomnographic parameters (apnea-hypopnea index and the lowest oxygen
      saturation) were collected and compared between groups.There were 298 boys and
      139 girls with the male to female ratio of 2.14:1. ADHD was found in 146 children
      including 105 boys and 41 girls with the male to female ratio of 2.56:1. Of these
      children, 31.62% and 35.46% had concomitant ADHD in children aged 4 to 5 years
      and those aged 6 to 11 years, respectively. In children aged 4 to 5 years, the
      incidence of allergic rhinitis was significantly higher (P = .016) and the
      adenoid hypertrophy was more severe (P = .001) in those with concomitant ADHD. In
      children aged 6 to 11 years, the tonsil hypertrophy was more severe in those with
      concomitant ADHD (P = .019). In children with concomitant ADHD, OSA-18 score was
      higher than in those with OSAHS alone (P < .001). Higher frequency of respiratory
      events (P < .001) and more severe hypoxia (P < .001) were found in children with
      concomitant ADHD than in those with OSAHS alone.As high as 30% of OSAHS children
      have concomitant ADHD, and the incidence of ADHD in OSAHS children is increasing
      over age. Boys are more likely to develop OSAHS and incidence of ADHD in OSAHS
      boys is higher than in OSAHS girls. In addition, risk factors of ADHD also vary
      between age groups. The ADHD is related to the severity of allergic rhinitis and
      adenoid hypertrophy in children aged 4 to 5 years, and to the severity of tonsil
      hypertrophy in children aged 6 to 11 years. Hypoxia may be an important factor
      causing ADHD. OSAHS should be treated as early as possible to reduce the
      incidence of ADHD in children.

PMID- 29049226
TI  - Regorafenib-induced retinal and gastrointestinal hemorrhage in a metastatic
      colorectal cancer patient with liver dysfunction: A case report.
AB  - RATIONALE: Regorafenib is effective for metastatic colorectal cancer but its
      toxicity such as hemorrhage should be considered. The safety of regorafenib for
      the patient with the liver disease is not known. PATIENT CONCERNS: Seventy-one
      year old man of colon cancer had myodesopsia and blood stool after 14 days from
      the initiation of regorafenib administration with 50% dose reduction due to liver
      dysfunction. DIAGNOSES: Fundus examination revealed hemorrhage of the retinal
      vein. INTERVENTIONS: Regorafenib treatment was discontinued and observational
      therapy was pursued. OUTCOMES: Retinal and gastrointestinal hemorrhage resolved
      in 1 week. LESSONS: Retinal hemorrhage should be considered as the differential
      diagnosis of myodesopsia in the patient treated by regorafenib. Safety and
      pharmacokinetic of continuous regorafenib administration for patients with liver
      dysfunction remains to be clarified.

PMID- 29049227
TI  - Association of central blood pressure and cardiovascular diseases in diabetic
      patients with hypertension.
AB  - To evaluate association of central blood pressure (BP) and cardiovascular disease
      (CVD) in diabetic patients with hypertension.This was a cross-section study and
      360 participants were enrolled. Baseline characteristics were collected and
      indices of central BP including central systolic/diastolic BP (SBP/DBP),
      augmentation index adjusted for 75 beats per minute of heart rate (AIx@75) were
      measured. Participants were separated into with and without CVD groups and
      between-group differences were assessed. Linear regression analysis was used to
      evaluate potential risk factors for increased AIx@75. Logistic regression
      analysis was used to evaluate association between central SBP and AIx@75 with
      CVD.Mean age was 50.6 years and male participants accounted for 57.8%. Thirty
      five and 43 participants had coronary heart disease and ischemic stroke. Compared
      with participants without CVD, those with CVD were more likely to be male and
      smokers and had higher glycated hemoglobin level. Additionally, participants with
      CVD had significantly higher central SBP and AIx@75 compared with those without
      CVD. Ageing, male gender, and presence of coronary heart disease and ischemic
      stroke were associated with increased AIx@75, whereas renin-angiotensin-axis
      inhibitor was associated with reduced AIx@75. After adjusted for traditional risk
      factors including brachial SBP, both central SBP, and AIx@75 remained
      significantly associated with CVD, with odds ratio and 95% confidence interval of
      1.09 (1.08-1.31) and 1.20 (1.15-1.42), respectively.Diabetic patients with
      hypertension, ageing, male gender, and presence of CVD are independent risk
      factors of central BP increase; and increased central SBP and AIx@75 are
      significantly associated with CVD.

PMID- 29049228
TI  - The efficiency of sonography in diagnosing volvulus in neonates with suspected
      intestinal malrotation.
AB  - This study is to prospectively evaluate the efficiency of sonography for volvulus
      diagnosis in neonates with clinically suspected intestinal malrotation.A total of
      83 patients with suspected intestinal malrotation who underwent detailed
      abdominal sonography and upper gastrointestinal contrast study were included.
      Malrotation was characterized by inversion of the superior mesenteric artery
      (SMA) and superior mesenteric vein (SMV) in sonographic examination. The
      "whirlpool sign" of Color Doppler Sonography was recognized as a characteristic
      for malrotation with volvulus. The degrees of rotation of the SMV winding around
      SMA were also detected by sonography. Surgery was performed in patients with
      sonography diagnosed malrotation.A total of 39 patients were sonographically
      diagnosed as malrotation which was subsequently confirmed by surgery. The
      sensitivity and positive predictive value of the sonographic diagnosis were both
      100% (39/39). The sensitivity, specificity and accuracy of "whirlpool sign" for
      the detection of midgut volvulus were 95.2% (20/21), 88.9% (16/18), and 92.3%
      (36/39), respectively. Greater degrees of rotation (equal or greater than 720
      degrees ) showed higher risk (odds ratio, 5.0; P < .01) for intestinal necrosis
      occurrence.Sonography is more accurate in diagnosing suspected malrotation than
      upper gastrointestinal contrast study. Specific sonographic "whirlpool sign"
      related to volvulus may be used as a potential indicator for intestinal necrosis.
      In addition, sonography can exclude malrotation and may help the diagnosis of
      other diseases, such as annular pancreas and duodenal atresia.

PMID- 29049229
TI  - Neck-to-shoulder pain as an unusual presentation of pulmonary embolism in a
      patient with cervical spinal cord injury: A case report.
AB  - RATIONALE: Information on referred pain can be helpful for diagnosing diseases of
      the visceral organs. Here, the authors report a patient with cervical spinal cord
      injury (SCI) who had referred pain at the right side from the neck to shoulder,
      as a presentation of pulmonary embolism (PE). PATIENT CONCERNS: A 55-year-old man
      with complete tetraplegia, due to cervical SCI after C5 and C6 vertebral body
      fracture, complained of right neck-to-shoulder pain (numerical scale rating: 6).
      Despite pain medication (meloxicam 15 mg, gabapentin 400 mg, and propacetamol HCl
      1 g), the pain was not reduced. Along with right neck-to-shoulder pain, he
      presented mild fever (37.8 degrees C) and mildly elevated respiratory rate (20
      breaths/min). D-dimer level was also mildly elevated to 6.09 mg/mL (normal value:
      < 0.5 mg/mL). DIAGNOSES: Computed tomography pulmonary angiography revealed PE in
      the right lower lobe pulmonary artery. INTERVENTIONS: For managing PE,
      rivaroxaban was administered for three days. OUTCOMES: After the administration
      of rivaroxaban, the patient's pain completely disappeared. LESSONS: This study
      shows that pain at the neck-to-shoulder area can occur following unexpected
      causes such as PE. Not limited to PE, the evaluation of diseases in the thoracic
      or abdominal organs is recommended if patients with cervical SCI present
      refractory pain in the dermatomes innervated by high cervical nerve roots.

PMID- 29049230
TI  - Goniosynechialysis combined with cataract extraction for iridoschisis: A case
      report.
AB  - RATIONALE: Iridoschisis is a rare eye disease. In this case report, we described
      the examination and diagnosis of a case of iridoschisis accompanied by secondary
      glaucoma. We also observed the effects of treating the patient with a combination
      of goniosynechialysis and cataract removal. PATIENT CONCERN: A 67-year-old female
      patient presented with decreased vision in both eyes. An eye examination
      indicated that visual acuities (VAs) were 20/100 and light perception in the
      right and left eyes, respectively. Both eyes exhibited shallow anterior chambers
      and narrow angles. The lower portion of the iris was loosened, and cable-like
      tissue was visible. The intraocular pressures in the right and left eyes were 22
      mmHg and 58 mmHg, respectively. At the time of presentation, no medication was
      being used. DIAGNOSES: The patient was diagnosed with iridoschisis [oculus
      sinister (OU), indicates left eye], secondary glaucoma (OU), senile cataract
      (OU), and pterygium (oculus uterque, indicates both eyes). INTERVENTION: After
      relevant examinations were conducted, goniosynechialysis and phacoemulsification
      with intraocular lens implantation were performed on the right eye under local
      anesthesia. OUTCOMES: Two days after surgery, the right eye had VA of 20/40 and a
      transparent cornea. The anterior chamber was deeper, and intraocular pressure had
      decreased to 16 mmHg. Three months after surgery, the patient exhibited improved
      VA in the right eye and a lower IOP of 11 mmHg. LESSONS: Relative to other
      approaches, goniosynechialysis combined with cataract removal is a better
      treatment option for iridoschisis complicated with closed-angle glaucoma
      triggered by peripheral anterior synechiae.

PMID- 29049231
TI  - Dose, duration and strain of bacillus Calmette-Guerin in the treatment of
      nonmuscle invasive bladder cancer: Meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Intravesical bacillus Calmette-Guerin (BCG) instillation is widely
      used as an adjuvant therapy after transurethral resection of bladder tumor
      (TURBT) in patients with intermediate- and high-risk nonmuscle invasive bladder
      cancer (NMIBC). However, the effective dose, duration, and strain of BCG have not
      yet been clearly determined. We aimed to elucidate the relationship between dose,
      duration, and strain of BCG and clinical outcomes in NMIBC patients treated with
      TURBT. METHODS: We conducted a literature search in Embase, Scopus, and PubMed
      databases for all relevant articles published up to October 2016 in accordance
      with the Preferred Reporting Items for Systematic Review and Meta-analysis
      guidelines. The relative risks of clinical outcomes, including recurrence,
      progression, cancer-specific mortality, and all-cause mortality according to dose
      (standard vs low), duration (induction vs maintenance), and strain of BCG were
      presented as the pooled risk ratio (RR) and 95% confidence interval (CI).
      RESULTS: Nineteen studies meeting the inclusion criteria were finally selected in
      this meta-analysis. The risk of recurrence was significantly highly observed in
      case of low-dose BCG (RR, 1.17; 95% CI 1.06-1.30) and induction BCG (RR, 1.33;
      95% CI 1.17-1.50) only group without heterogeneity among the included studies.
      Although there were no significant differences between dose or duration and other
      clinical outcomes. On direct comparison in each study comparing BCG strains, the
      Tice stain showed a relatively high probability of recurrence compared with the
      Connaught (RR, 1.29; 95% CI 1.01-1.64) and RIVM (RR, 2.04, 95% CI 1.28-3.25)
      strains. Funnel plot testing revealed no significant publication bias.
      CONCLUSION: The use of standard dose and maintenance BCG instillation may be
      effective to reduce recurrence rate after TURBT for NMIBC. Further large scale,
      well-designed, and prospective studies, with stratification of the patients into
      risk group at randomization, will be required to determine the optimal guideline
      of BCG use to improve clinical outcomes in NMIBC.

PMID- 29049232
TI  - Case report: Central nervous system involvement of human graft versus host
      disease: Report of 7 cases and a review of literature.
AB  - RATIONALE: Central nervous system (CNS) involvement of graft versus host disease
      (GvHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). Chronic CNS GvHD symptoms are heterogeneous and
      include cerebrovascular manifestations, demyelinating disease and immune-mediated
      encephalitis. CNS-Acute GvHD is not formally defined in literature. PATIENTS
      CONCERNS AND DIAGNOSES: We report 7 cases of CNS-GvHD among which two had
      histological-proven disease. We reviewed 32 additional cases of CNS GvHD
      published in literature since 1990. In this cohort, 34 patients were transplanted
      for hematologic malignancies, and 5 for non-malignant hematopoiesis disorders. Of
      these patients, 25 had a history of chronic GvHD and immunosuppressive treatment
      had been decreased or discontinued in 14 patients before neurological symptoms
      onset. Median neurological disorder onset was 385 days [7-7320]. Patients had
      stroke-like episodes (n = 7), lacunar syndromes (n = 3), multiple sclerosis-like
      presentations (n = 7), acute demyelinating encephalomyelitis-like symptoms (n =
      4), encephalitis (n = 14), mass syndrome (n = 1), and 3 had non-specific
      symptoms. Median neurological symptoms onset was 81.5 days [7-1095] for patients
      without chronic GVHD history versus 549 days [11-7300] for patients with chronic
      GVHD (P = 0.001). Patients with early involvement of CNS after allo-HSCT and no
      chronic GVHD symptoms were more frequently suffering from encephalitis (64%
      versus 28%, P = 0.07), whereas stroke-like episodes and lacunar symptoms were
      less frequent (9% versus 36%, P = 0.13). INTERVENTIONS: 34 patients with CNS-GvHD
      were treated with immunosuppressive therapy, including corticosteroids for 31 of
      them. Other treatments were intravenous immunoglobulin, plasmapheresis,
      cyclophosphamide, calcineurin inhibitors, mycophenolic acid, methotrexate and
      etoposide. OUTCOMES: 27 patients achieved a response: 10 complete responses, 15
      partial responses and 2 transient responses. Of 25 patients with sufficient
      follow-up, 7 were alive and 18 patients deceased after CNS-GvHD diagnosis.
      LESSONS: CNS-related GvHD is a rare cause of CNS disorders after allo-HSCT and is
      associated with a poor prognosis.

PMID- 29049233
TI  - Pediatric types I and VI choledochal cysts complicated with acute pancreatitis
      and spontaneous perforation: A case report and literature review.
AB  - RATIONALE: Choledochal cysts are a congenital disorder of the common bile duct
      that can cause progressive biliary obstruction and biliary cirrhosis. They were
      classified by Todani into five types. Of these, type VI choledochal cysts are
      rarely reported in the literature. PATIENT CONCERNS: A 22-month-old girl
      presented with intermittent epigastralgia for approximately 10 days and fever for
      three days. Fasting and total parenteral nutrition were administered after
      admission. However, sudden onset of severe epigastric pain occurred. An abdominal
      sonogram showed turbid ascites and peritonitis was impressed. DIAGNOSES: An
      emergent exploratory laparotomy was performed, and perforation of the posterior
      wall of types I and VI choledochal cysts was observed. INTERVENTIONS:
      Intraoperative cholangiography revealed concomitant types I and VI choledochal
      cysts with stricture of the distal common bile duct. Definite surgery for
      resection of the choledochal cysts and gallbladder was performed with Roux-en-Y
      choledochojejunostomy. OUTCOMES: The patient had no evidence of ascending
      cholangitis at three years after the operation. LESSONS: Type VI choledochal
      cysts are rarely reported in the literature. To our knowledge, this is the first
      reported pediatric case of concomitant types I and VI choledochal cysts
      complicated with acute pancreatitis and spontaneous perforation.

PMID- 29049234
TI  - Case report: Features of hand, foot and mouth disease in neonates.
AB  - RATIONALE: Hand, foot and mouth disease (HFMD) is caused by enterovirus. The
      virus may exist in secretions. PATIENT CONCERNS: Five neonates had symptoms of
      fever and maculopapular rashes involving face, trunk, breech, arms, and legs,
      especially scattering on palms and feet. Blood, oropharyngeal fluid, urine, and
      cerebrospinal fluid (CSF) samples were collected and detected for further
      diagnoses with the consent of the infants' parents. Some of them suffered aseptic
      meningitis. DIAGNOSES: They were diagnosed as HFMD with CSF enterovirus positive.
      INTERVENTIONS: All of them continued breastfeed. Water bag was used during the
      pyrogenic stage. Antibiotics were administrated at first and withdrawn as soon as
      possible. OUTCOMES: None of them developed into brainstem encephalitis or
      pulmonary edema and they all recovered well. LESSONS: HFMD is more common in
      neonates than it has been thought. Enterovirus may exist in neonatal CSF and
      cause CSF cell to increase similar to purulent meningitis. Medical history,
      physical examination, and CSF enterovirus detection are important in making
      correct diagnosis. Unlike bacterial infection, HFMD is a self-limited disease.
      Once HFMD is determined and bacterial infection is ruled out, antibiotics should
      be avoided.

PMID- 29049235
TI  - Comparing the protective performances of 3 types of N95 filtering facepiece
      respirators during chest compressions: A randomized simulation study.
AB  - OBJECTIVE: Healthcare providers in emergency departments should wear respirators
      for infection protection. However, the wearer's vigorous movements during
      cardiopulmonary resuscitation may affect the protective performance of the
      respirator. Herein, we aimed to assess the effects of chest compressions (CCs) on
      the protective performance of respirators. METHODS: This crossover study
      evaluated 30 healthcare providers from 1 emergency department who performed CC
      with real-time feedback. The first, second, and third groups started with a cup
      type, fold-type, and valve-type respirator, respectively, after which the
      respirators were randomized for each group. The fit factors were measured using a
      quantitative fit testing device before and during the CC in each experiment. The
      protection rate was defined as the proportion of respirators achieving a fit
      factor >=100. RESULTS: The fold-type respirator had a significantly greater
      protection rate at baseline (100.0% +/- 0.0%) compared to the cup-type (73.6% +/-
      39.6%, P = .003) and valve-type respirators (87.5% +/- 30.3%, P = .012). During
      the CC, the fit factor values significantly decreased for the cup-type (44.9% +/-
      42.8%, P < .001) and valve-type respirators (59.5% +/- 41.7%, P = .002), but not
      for the fold-type respirator (93.2% +/- 21.7%, P = .095). CONCLUSIONS: The
      protective performances of respirators may be influenced by CC. Healthcare
      providers should identify the respirator that provides the best fit for their
      intended tasks.

PMID- 29049236
TI  - Lipoma of the middle finger: A case report and review of literature.
AB  - RATIONALE: Lipomas originated from fingers are rare and the dissection is
      necessary when the lipomas limit the finger movement or cause pain. PATIENT
      CONCERNS: A 57-year-old male was admitted to our department due to a painless
      swelling on the volar side of the middle finger of the right hand. The flexion
      movement of the distal interphalangeal joint was limited. DIAGNOSES: Imaging
      studies and open biopsy confirmed that it was a finger lipoma. INTERVENTIONS: An
      excisional biopsy was performed. OUTCOMES: The patient recovered completely after
      two weeks. LESSONS: Based on this case and literature we reviewed, ultrasound and
      MRI should be used to diagnose the finger lipoma and excision was the main
      treatment option.

PMID- 29049237
TI  - Effect and safety of cytokine-induced killer (CIK) cell immunotherapy in patients
      with breast cancer: A meta-analysis.
AB  - BACKGROUND: Breast cancer (BC) is considered a systemic disease with a primarily
      locoregional component. The accumulation of basic researches and clinical studies
      related to cytokine-induced killer (CIK) cells has confirmed their safety and
      feasibility in treating BC. By searching the PubMed, Embase, CNKI, and Wanfang
      databases, we conducted a meta-analysis to assess the efficacy and safety of
      DC/CIK plus chemotherapy regimen (Exp) compared with chemotherapy (Con) alone
      regimen for breast carcinoma. Studies were pooled, and the relative risk (RR) and
      its corresponding 95% confidence interval (CI) were calculated. METHODS: Eleven
      relevant articles were included in this meta-analysis. We observed that complete
      response (CR) (RR = 1.54, 95% CI: 1.09-2.19, Pheterogeneity = .994, I = 0%),
      partial response (PR) (RR = 1.33, 95% CI: 1.11-1.59, Pheterogeneity = .802, I =
      0%) and overall response rate (ORR) (RR = 1.37, 95% CI: 1.20-1.57, Pheterogeneity
      = .619, I = 0%) in BC patients treatment with DC/CIK plus chemotherapy regimen
      was improved than that with chemotherapy alone. There was no difference in the
      incidence of leukopenia, thrombocytopenia, hair loss, nausea/vomiting, hepatic
      complications, and neurologic complications in BC patient's treatment with DC/CIK
      plus chemotherapy regimen and with chemotherapy alone. RESULTS: Compared to
      chemotherapy alone, DC/CIK plus chemotherapy treatment significantly increased
      CR, PR, and ORR; however, there was no difference between the safeties.
      CONCLUSION: DC/CIK plus chemotherapy treatment may be a valuable new option for
      the treatment of breast carcinoma in women. The present study, therefore,
      provides valuable information to help physicians make treatment decisions for
      their patients with BC.

PMID- 29049238
TI  - Age- and sex-related differences in corneal epithelial thickness measured with
      spectral domain anterior segment optical coherence tomography among Egyptians.
AB  - Is to measure the corneal epithelial thickness (CET) in a group of healthy
      Egyptian population and to investigate its variation with age and sex using
      spectral domain-anterior segment optical coherence tomography (SD-AS-OCT).This
      cross-sectional observational study includes 240 eyes of 120 healthy individuals
      (60 men, 60 women). Each gender was divided into 4 equal groups according to age
      as follows (18-29 years), (30-44 years), (45-59 years), and (60-80 years). The
      CET in 17 points over a corneal diameter of 6.0 mm was measured in each subject
      by SD-AS-OCT. The regional thickness changes were compared in different age
      groups of each gender separately and the correlations between the CET, age, and
      gender were analyzed.The CET of the central cornea (2 mm), the paracentral and
      the midperipheral zones (2-5 and 5-6 mm, respectively) of all males and females
      groups demonstrates highly significant changes with age (P < .001) with no
      significant difference between males and females. The measured parameters in the
      2 age groups below 45 and above 45 years old revealed statistically significant
      difference with lower values in the elderly group (P < .001).The CET became
      thinner with age in the central, paracentral, and midperipheral zones in both
      genders and there is no difference between males and females. These findings
      could be valuable in refractive surgeries especially in age over 45.

PMID- 29049239
TI  - Clinical features and diagnosis of chronic pulmonary aspergillosis in Chinese
      patients.
AB  - Chronic pulmonary aspergillosis (CPA) has recently been recognized as a
      significant global health burden. In China, the diagnosis of CPA is still
      unfamiliar to most doctors. The aim of this study was to demonstrate the clinical
      manifestations and diagnoses of CPA in China.A multidisciplinary team of doctors
      retrospectively screened 690 records of patients diagnosed with pulmonary
      aspergillosis from January 2000 to December 2016 at Peking Union Medical College
      Hospital, Beijing, China. Of these, 69 patients were diagnosed with CPA. The
      patients' clinical characteristics were then retrieved and analyzed. Demographic,
      laboratory, and radiological data for these patients were compared by CPA type.Of
      the 69 patients diagnosed with CPA, 10 patients were diagnosed with chronic
      cavitary pulmonary aspergillosis (CCPA), 15 patients with semi-invasive
      aspergillosis (SAIA), 41 patients with simple aspergilloma, and 3 patients with
      Aspergillus nodule. Further, 53.3% of the SAIA patients were obviously
      immunocompromised, and 60% of the CCPA patients, 26.7% of the SAIA patients, 7.3%
      of the simple aspergilloma cases were mildly immunocompromised. Previous
      underlying lung abnormalities were observed in 20% of CCPA patients, 53.3% of
      SAIA patients, and 80.5% of simple aspergilloma patients. The most common
      symptoms in the CPA patients were cough (92.8%), hemoptysis (63.8%), chronic
      sputum (23.2%), and fever (17.4%). The most common computerized tomography
      abnormalities were cavities (94.2%), nodule (84.1%), consolidation (4.3%),
      pleural thickening (2.9%), and infiltration (2.9%). CCPA, SAIA and simple
      aspergilloma patients were significantly different with respect to their course
      before diagnosis, constitutional symptoms, fever, hemoptysis, breathlessness,
      white blood cell count, erythrocyte sedimentation rate, high-sensitivity C
      reactive protein count, presence of nodule, and presence of a solitary lesion
      (all P < .05). Furthermore, SAIA patients had a significantly shorter course
      before diagnosis and a significantly higher white blood cell count compared with
      CCPA patients (both P < .01).In China, underlying systemic immunocompromising
      conditions and lung diseases with mechanical impediments contribute to CPA.
      Simple aspergillosis was the most common diagnosis in CPA patients. The imaging
      characteristics of simple aspergillosis and Aspergillus nodules were quite
      discriminable, while CCPA, and SAIA were similar in their clinical and
      radiological features. Distinguishing between CCPA and SAIA depends mainly on the
      physician's clinical judgment.

PMID- 29049240
TI  - The thorax trauma severity score and the trauma and injury severity score: Do
      they predict in-hospital mortality in patients with severe thoracic trauma?: A
      retrospective cohort study.
AB  - Several scoring systems are commonly used to evaluate severity in patients with
      traumatic injuries. However, there is no generally accepted standard scoring
      system to assess the severity of thoracic trauma, specifically in patients who
      have sustained severe injuries. The present study aimed to evaluate the validity
      of the trauma and injury severity score (TRISS) and the thorax trauma severity
      score (TTSS) as predictors of in-hospital mortality in patients with severe
      thoracic trauma.We conducted a retrospective, consecutive review of the medical
      records of patients with severe thoracic trauma who were managed at our
      institution between January 2005 and December 2015. Inclusion criteria were
      patients with severe thoracic injury (injury severity score > 18) who required
      intensive care therapy and who had no local or systemic infection. We analyzed
      the association between the trauma severity scores (TTSS and TRISS) and in
      hospital mortality in these patients. We also determined the predictive value of
      the scores using receiver-operating characteristic (ROC) curves.A total of 228
      patients with severe thoracic trauma were included in this study. The in-hospital
      mortality rate was 21.9%. There was a statistically significant association
      between the TRISS and in-hospital mortality (P < .001), but the association
      between the TTSS and in-hospital mortality was not statistically significant (P =
      .547). The ROC curve demonstrated adequate discrimination, as demonstrated by an
      area under the curve value of 0.787 for the TRISS. At a cut-off value of 25.9%,
      the TRISS had a sensitivity of 83.6% and specificity of 73.5% to predict in
      hospital mortality.The present study demonstrated that the TRISS, but not the
      TTSS, can be used to predict in-hospital mortality in patients with severe
      thoracic trauma; hence, additional prospective studies are required.

PMID- 29049241
TI  - Evaluation of the reduction in central and peripheral arterial blood pressure
      following an oral glucose load.
AB  - The clinical significance of measuring central arterial blood pressure has been
      recently discussed. Although the postprandial reduction in blood pressure is well
      known, postprandial changes in central blood pressure have not been intensively
      studied. The present study investigated differences in the reduction of central
      and peripheral arterial blood pressure after administration of an oral glucose
      load.An oral glucose tolerance test (75 g) was performed in 360 participants in
      our physical checkup program. Brachial and central systolic blood pressures were
      assessed before and after the glucose load. Central arterial blood pressure was
      measured noninvasively using an automated device.The mean age was 53.6 +/- 8.2
      years. Both brachial (127.9 +/- 17.7 to 125.0 +/- 16.3 mm Hg) and central
      arterial blood pressures were significantly decreased after an oral glucose load
      (118.9 +/- 17.9 to 112.8 +/- 16.8 mm Hg). The reduction in blood pressure was
      greater in central (7.3 +/- 11.5 mm Hg) than in brachial blood pressure
      measurements (3.4 +/- 11.3 mm Hg, P < .001). Extreme blood pressure reduction
      (>20 mm Hg) was recorded more frequently in central (n = 43, 12.3%) than brachial
      blood pressure measurements (n = 20, 5.6%).An oral glucose load decreases both
      central and brachial systolic blood pressure, with more pronounced effects on
      central blood pressure. Postprandial reductions in blood perfusion of the
      important organs such as the brain may be underestimated when postprandial BP
      reduction is assessed using brachial BP measurements.

PMID- 29049242
TI  - The prevalence of PI*S and PI*Z SERPINA1 alleles in healthy individuals and COPD
      patients in Saudi Arabia: A case-control study.
AB  - Alpha-1 antitrypsin (AAT) is an acute phase protein produced in hepatocytes. Its
      deficiency affects the lungs and liver. A case-control study was carried out to
      determine the prevalence of 2 common deficiency alleles, PI*S and PI*Z, for alpha
      1 antitrypsin deficiency (AATD) in both healthy and chronic obstructive
      pulmmonary disease (COPD)-affected Saudi populations and to clarify the
      importance of genetic tests in the screening of people at risk for COPD.One
      thousand blood samples from healthy individuals and 1000 from COPD-affected Saudi
      individuals were genotyped for the above-mentioned alleles, using real-time
      polymerase chain reaction (PCR), with the exclusion of any other nationalities.
      Data were analyzed by determining the allele and genotype frequencies through
      gene counting and its confidence intervals. The allele frequencies, derived by
      the Hardy-Weinberg equilibrium method, were analyzed by Pearson Chi-squared
      tests. The confidence intervals for genotype frequencies were calculated using
      exploratory software for confidence intervals.Of the 1000 COPD patients included
      in our study, the prevalence of PI*S and PI*Z was 21.8% and 7.7%, respectively,
      while within the 1000 normal samples, these alleles occurred in 8.9% of patients
      for PI*S and 1.6% for PI*Z. The AAT deficiency genotype frequencies (PI*ZZ,
      PI*SS, and PI*SZ) were 6.5 per 1000 and 87 per 1000 for normal and COPD-affected
      Saudi individuals.Our results indicated a high prevalence of AATD alleles in the
      normal Saudi population and an association between AAT deficiency and pulmonary
      disease development. Additionally, our research confirms the importance of
      genetic screening to achieve early and accurate diagnosis of AATD.

PMID- 29049243
TI  - Rare case of pulmonary lymphomatoid granulomatosis in conjunction with
      tuberculosis: A case report.
AB  - RATIONALE: Lymphomatoid granulomatosis is a very rare Epstein-Barr virus-driven
      lymphoproliferative disease. This disease has high mortality owing to its low
      incidence in conjunction with nonspecific presentations, which contribute to
      delays in diagnosis. PATIENT: An 87-year-old male had a week-long history of
      intermittent fever and general weakness. A chest radiograph showed multifocal
      patchy consolidations with nodular lesions. DIAGNOSES: Open lung biopsy using
      video-assisted thoracic surgery resulted in a diagnosis of grade III lymphomatoid
      granulomatosis. Three days after surgery, Mycobacterium tuberculosis complex was
      identified from the culture of sputum samples collected at admission.
      INTERVENTION AND OUTCOMES: Antituberculous treatment was commenced first.
      However, after 34 days of antituberculosis medication, the patient died owing to
      aggravated lymphomatoid granulomatosis. LESSONS: This case highlights the fact
      that rare diseases should also be considered in differential diagnosis,
      particularly with a common presentation such as multiple lung nodules.
      Furthermore, a diagnosis of pulmonary lymphomatoid granulomatosis was made after
      open lung biopsy. To our knowledge, this is the first case of lymphomatoid
      granulomatosis coexisting with active tuberculosis in the Republic of Korea,
      where tuberculosis is endemic.

PMID- 29049244
TI  - Isolated heptadactylia: A case report of central polydactyly of the foot.
AB  - RATIONALE: Heptadactylia is a rare congenital disorder from the polydactyly
      family. Polydactyly is generally classified into 3 major groups: preaxial (medial
      ray), postaxial (lateral ray), and central polydactyly. Most common cases are
      related to preaxial or postaxial polydactyly. The rarity of central polydactyly
      can be explained in 3 ways. First, central polydactyly with duplication appearing
      on metatarsal is pretty uncommon. Second, the duplication appears isolated on the
      foot. Polydactyly is mostly associated with other physical defects or others
      duplications. Last, the duplication of the digital rays does not appear once but
      twice concerning all the digital rays and makes 7 functional toes appear. We
      describe this malformation with supporting iconography and radiography as well as
      its surgical management and functional results. PATIENT CONCERNS: We analyzed an
      original case of isolated heptadactylia on the foot of a 14-month-old girl. The
      supernumerary toes made it impossible for the child to wear standard shoes and
      her parents were worried about this problem. DIAGNOSES: Clinical foot examination
      and radiographs revealed the presence of 7 complete rays. Every toe was composed
      of phalanx and metatarsal ray. There was no other congenital deformity.
      INTERVENTIONS: Decision was made to resect the second and third rays (the two
      most misaligned toes in our consideration). The first stage of surgery was the
      ray resection and the second stage was the reconstruction of the intermetatarsal
      ligament to achieve a good functional and cosmetic results. OUTCOMES: After wound
      healing, the child was able to walk alone while wearing normal shoes. LESSONS: We
      demonstrated that treatment of foot polydactyly requires careful preoperative
      assessment, including radiographs and photography. A good clinical evaluation of
      the medial polydactyly improves type-specific recognition which may enhance the
      accuracy of surgical treatment. Polydactyly is frequently associated with other
      malformations. We recommend performing a general clinical examination to exclude
      concomitant malformations. We recommend surgical treatment around the onset of
      walking.

PMID- 29049245
TI  - Sacral root injury during trans-sacral epiduroscopic laser decompression: A case
      report.
AB  - RATIONALE: Trans-sacral epiduroscopic laser decompression (SELD) is reported to
      have strong positive short-term effects in controlling lower back pain (LBP) or
      radicular leg pain following herniated lumbar disc (HLD). However, little is
      known about the possible complications following SELD. PATIENT CONCERNS: A 36
      year-old man received SELD with YAG laser for controlling LBP and radicular pain
      due to HLD on L5-S1. However, after SELD, voiding and defecation difficulties and
      sensory deficits on the S3-5 dermatome were presented. DIAGNOSES: An areflexic
      neurogenic bladder was demonstrated by a urodynamic study four days after onset
      of sacral nerve root injury symptoms. In the electromyogram study, latency of
      electrically induced bulbocavernosus reflex (BCR) was delayed on both sides at
      four days after symptom onset. Based on the patient's symptoms and the results of
      the clinical evaluation, we diagnosed the patient as having an injury in the
      sacral nerve roots. INTERVENTIONS: The patient was observed without any specific
      medication. OUTCOMES: Three months after symptom onset, the patient's voiding and
      defecation difficulties were nearly completely recovered. LESSONS: In this study,
      we described a patient who showed neurogenic bladder and bowel and sensory
      deficits in the S3 to S5 dermatome due to sacral nerve root injury after SELD.
      During SELD, clinicians should be mindful of the possibility of injury to sacral
      nerve roots.

PMID- 29049246
TI  - Synergistic ELCA-aspiration-DES thrombus removal strategy-embolus impact in high
      risk plaque: A case report.
AB  - RATIONALE: Thin-cap fibroatheroma (TCFA) and red thrombus are suggested as a high
      risk of embolic complications during percutaneous coronary intervention (PCI).
      Intracoronary aspiration procedures occasionally result in either an insufficient
      thrombus removal or provide no significant effects on TCFA. PATIENT CONCERNS: A
      76-year-old male underwent coronary angiography for chest pain. DIAGNOSES:
      Coronary angiography revealed a tight stenosis at the right coronary artery which
      resulted in treatment by PCI. Optical frequency domain imaging (OFDI) delineated
      a red thrombus with TCFA. INTERVENTIONS: To avoid embolic complications, excimer
      laser coronary angioplasty (ELCA) was applied with intracoronary aspiration
      before drug-eluting stent (DES) implantation. OUTCOMES: The red thrombus was
      vaporized by ELCA in an energy-intensity dependent manner and subsequently
      removed by intracoronary aspiration. The fibrous cap of TCFA was dissected with
      the material beneath the cap ablated by ELCA and extensively removed by
      intracoronary aspiration. DES implantation and postdilatation achieved an optimal
      result without flow compromise. This combined synergistic strategy of ELCA
      aspiration-DES yielded a successful outcome. LESSONS: A synergistic embolus
      removal strategy combining ELCA, aspiration and DES implantation is a promising
      option for the treatment of high-risk plaque with potential embolic
      complications.

PMID- 29049247
TI  - Increased circulating Th22 cells in patients with acute gouty arthritis: A
      CONSORT-compliant article.
AB  - BACKGROUND: T-helper 22 (Th22) cells are involved in host immunity against
      pathogen invasion and have been implicated in the pathogenesis of inflammatory
      diseases. However, the roles of Th22 cells in acute gouty arthritis remain
      unclear. METHODS: A case-control study was employed to illustrate the clinical
      significance of Th22 cells in acute gouty arthritis. In this study, 27 patients
      with acute gouty arthritis, 22 patients with intercritical gout (IG), and 20
      healthy controls were recruited, and peripheral blood cells and plasma were
      collected for the detection of Th22, Th17, and Th1 cells, and plasma interleukin
      (IL)-22. RESULTS: The relative and absolute numbers of Th22 and Th17 cells were
      significantly higher in patients with acute gouty arthritis than in patients with
      IG and healthy controls. Plasma IL-22 levels were consistently higher in patients
      with acute gouty arthritis than in patients with IG and healthy controls (P <
      .05). Th22 cell numbers were positively correlated with Th1 (r = 0.648, P < .05)
      and Th17 (r = 0.379, P < .05) cell numbers in patients with gout. Moreover, Th22
      cell numbers and plasma IL-22 levels were positively correlated with C-reactive
      protein levels (Th22: r = 0.444, P < .05; IL-22: r = 0.282, P < .05). CONCLUSION:
      Our results indicate that peripheral blood levels of Th22 cells increase during
      acute gouty arthritis suggesting a role for these cells in the pathophysiology of
      the disease.

PMID- 29049248
TI  - Item response theory-based validation of a short form of the Eating Behavior
      Scale for Japanese adults.
AB  - Obesity has become a serious social problem in industrialized countries in recent
      years. Clinically, although the evaluation of dietary behavior abnormalities is
      as important as any method of risk assessment for obesity, almost all the
      existing scales with many items may have numerous practical clinical
      difficulties. In this study, we aimed to prepare a short questionnaire to assess
      the dietary behavior abnormalities related to obesity. A total of 1032
      individuals aged 20 to 59 years participated in the present study. Using item
      response theory (IRT), we selected the items for a short version from among 30
      items of Sakata Eating Behavior Scale (EBS), which is widely used in Japan. As a
      result of the IRT-based analysis on the original 30-item version, 7 items were
      adopted as the short version. The correlation between the total score of the
      original EBS and the EBS short form was extremely high (r = 0.93, P = .001). In
      examining the criterion validity, for all participants (n = 1032), male (n =
      516), and female (n = 516), the correlation coefficients between the total score
      of the EBS short form and body mass index (BMI) were r = 0.26, r = 0.28, and r =
      0.28, respectively. The results of the receiver operating characteristic analysis
      was performed with obesity BMI > 25 kg/m as a dependent variable, the value of
      the area under the curve in the ROC was significantly higher in the 7-item
      version than in the total score of the original items (P = .0005). In conclusion,
      the 7-item EBS short form was created. Furthermore, it was found that the EBS
      short form is a reliable and valid measure that can be used as an indicator of
      obesity in both clinical and research settings.

PMID- 29049249
TI  - Cardiac conduction disturbances and aging in patients with Duchenne muscular
      dystrophy.
AB  - The majority of patients with Duchenne muscular dystrophy (DMD) have
      electrocardiographic abnormalities, but the clinical significance of conduction
      disturbances remains unclear. This study aimed to evaluate age-dependent cardiac
      conduction disturbances by electrocardiogram (ECG) to identify risks of complete
      atrioventricular (AV) block in this patient population.In total, 47 patients with
      DMD (age, >=20 ys) who recorded ECGs at our hospital from July 2015 to June 2016
      were included in this study. The PR interval and QRS duration in their previous
      ECGs were analyzed retrospectively. Associations between ECG findings and left
      ventricular (LV) systolic function obtained from the latest echocardiography were
      examined.The mean age of patients was 27.6 +/- 6.0 years, and the mean
      observation period was 9.8 +/- 3.7 years. The PR interval gradually increased
      with age, but no ECGs showed an abnormally prolonged PR interval. On the other
      hand, the QRS duration tended to increase progressively with age, and some
      patients had an abnormally prolonged QRS duration. The QRS duration was not
      correlated with LV systolic function (P = 0.867). One patient who developed a
      complete AV block had a drastically prolonged QRS duration before the onset of
      the disorder.The QRS duration tended to increase progressively with age,
      irrespective of LV systolic function in patients with DMD. Attention should be
      paid to the QRS duration as an indicator of risk for complete AV block in older
      patients.

PMID- 29049250
TI  - Comparison of the efficacy of Gd-EOB-DTPA-enhanced magnetic resonance imaging and
      magnetic resonance elastography in the detection and staging of hepatic fibrosis.
AB  - The present study compared the efficacy of gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance
      imaging (MRI) and magnetic resonance elastography (MRE) in the estimation of
      hepatic fibrosis stages with histopathologic correlation.This retrospective study
      included 104 patients (87 men and 17 women; mean age, 60.6 +/- 10.6 years) with
      chronic liver disease who underwent both Gd-EOB-DTPA-enhanced MRI and MRE. The
      relative enhancement (RE) ratio of the liver parenchyma and the contrast
      enhancement index (CEI) were calculated as (SIpostliver - SIpreliver)/SIpreliver
      and SIpost/SIpre, respectively, where SIpost and SIpre were the liver-to-muscle
      signal intensity ratios on the hepatobiliary phase images and noncontrast
      enhanced images, respectively. The liver stiffness values were measured using MRE
      stiffness maps. The diagnostic performance of MRE, RE ratios, and CEI values for
      hepatic fibrosis staging were compared.The distribution of fibrosis stages was as
      follows: F0, n = 3 (2.9%); F1, n = 12 (11.5%); F2, n = 17 (16.3%); F3, n = 26
      (25.0%); and F4, n = 46 (44.2%). MRE, RE ratios, and CEI values correlated
      significantly with hepatic fibrosis (rs = .79, -.35, -.25, respectively, P <
      .05). MRE showed a significantly higher diagnostic performance than did RE ratios
      and CEI values for each fibrosis stage, except while distinguishing the F1
      fibrosis stage (CEI, P = .15). A cutoff value of RE ratio = 0.89 can be used to
      identify patients with significant hepatic fibrosis, with positive predictive
      value, sensitivity, specificity, and negative predictive value of 93.2%, 61.8%,
      73.3%, and 24.4%, respectively.Gd-EOB-DTPA-enhanced MRI can potentially predict
      significant hepatic fibrosis. However, the diagnostic performance of MRE for
      hepatic fibrosis staging was superior to that of Gd-EOB-DTPA-enhanced MRI.

PMID- 29049251
TI  - Esmolol pretreatment attenuates heart rate increase and parasympathetic
      inhibition during rapid increases in desflurane concentration: A preliminary
      randomized study.
AB  - BACKGROUND: Rapid increases in desflurane concentration can transiently increase
      the heart rate (HR). Esmolol possesses a high beta1-adrenoceptor selectivity and
      a short duration of action. This preliminary study aimed at investigating the
      effects of esmolol on the HR and autonomic modulation during a desflurane-induced
      HR increase. METHODS: American Society of Anesthesiologists physical status I
      female subjects, aged 20 to 50 years, who were undergoing minor breast surgery
      were randomly assigned to 2 groups. Rapid increases in desflurane concentration
      were commenced after induction of anesthesia. Each subject received either i.v.
      saline (control group) or esmolol 0.5 mg/kg (esmolol group) before desflurane
      inhalation. Using time-frequency spectral analysis of HR variability, the HR
      indices were studied at baseline, postinduction, posttreatment, as well as at
      minimal alveolar concentrations of desflurane reaching 1.0, 1.3, and 1.5. The low
      frequency (LF) power is influenced by both the sympathetic and parasympathetic
      activity, whereas the high frequency (HF) power reflects the parasympathetic
      activity. The LF/HF ratio is thought to reflect either sympathovagal balance or
      sympathetic modulation. RESULTS: Electrocardiograms for data analysis were
      obtained from 8 subjects in each group. Rapid increases in desflurane
      concentration after induction caused a HR increase. Both the corresponding LF and
      HF powers were low and the LF/HF ratio remained unchanged. This indicates that
      the desflurane-induced HR increase may be attributed to parasympathetic
      inhibition and may be independent of sympathetic activation. Esmolol pretreatment
      effectively attenuated desflurane-induced HR increase. Moreover, subjects
      receiving esmolol pretreatment had increased LF and HF powers, but did not have
      changes in their LF/HF ratios, as compared to those without esmolol. CONCLUSION:
      Esmolol pretreatment attenuates HR increase and parasympathetic inhibition during
      rapid increases in desflurane concentration.

PMID- 29049252
TI  - Prognostic role of FDG PET/CT in patients with differentiated thyroid cancer
      treated with 131-iodine empiric therapy.
AB  - BACKGROUND: To assess the long-term prognostic value of F-fluorodeoxyglucose
      (FDG) positron emission tomography/computed tomography (PET/CT) in patients with
      differentiated thyroid carcinoma (DTC) undergoing empiric radioiodine (RAI)
      therapy due to raising values of thyroglobulin (Tg). METHODS: Forty-nine patients
      with histological diagnosis of DTC (31 with papillary and 18 with follicular
      carcinoma) follow-up for a mean period of 7.9 +/- 5 years after empiric RAI
      therapy were retrospectively analyzed. RESULTS: FDG-PET/CT was negative in 15
      (30.6%) patients and positive in 34 (69.4%), whereas postradioiodine therapy
      whole body scan (t-WBS) was negative in 16 (32.7%) and positive in 33 (67.3%)
      patients. FDG-PET/CT and t-WBS were in agreement in 32 patients (7 both negative
      and 25 both positive); on the contrary, in 17 patients there was disagreement
      between FDG-PET/CT and t-WBS (P =ns). At short-term follow-up, Tg normalized in
      19 (38.8%) patients and was unchanged or increased in 30 (61.2%). Of the 15
      patients with negative FDG-PET/CT, 11 (73.3%) showed Tg normalization, whereas of
      the 34 patients with positive FDG-PET/CT, only 8 (23.5%) had Tg normalization
      (chi =8.9, P < .005). At multivariate analysis, FDG-PET/CT and Tg normalization
      at short-term follow-up were independent predictors of disease-free survival (chi
      =26.3, P < .0001), while Tg normalization was the only variable associated with
      overall survival chi =7.2, P < .01). CONCLUSION: FDG-PET/CT in association with
      Tg normalization at short-term follow-up may be useful for long-term prognostic
      stratification in DTC patients.

PMID- 29049253
TI  - Clinical efficacy analysis of Ahmed glaucoma valve implantation in neovascular
      glaucoma and influencing factors: A STROBE-compliant article.
AB  - This study aimed to evaluate the efficacy of Ahmed glaucoma valve (AGV)
      implantation in treating neovascular glaucoma (NVG) and to analyze the factors
      influencing the surgical success rate.This is a retrospective review of 40 eyes
      of 40 NVG patients who underwent AGV implantation at Xiangya Hospital of Central
      South University, China, between January 2014 and December 2016. Pre- and
      postoperative intraocular pressure (IOP), visual acuity, surgical success rate,
      medications, and complications were observed. Surgical success criteria were
      defined as IOP <=21 and >6 mm Hg with or without additional medications. Kaplan
      Meier survival curves and Multivariate cox regression analysis were used to
      examine success rates and risk factors for surgical outcomes.The mean follow-up
      period was 8.88 +/- 3.12 months (range: 3-17). IOP declined at each visit
      postoperatively and it was statistically significant (P < .001). An average of
      3.55 +/- 0.86 drugs was applied preoperatively, while an average of 0.64 +/- 0.90
      drugs was used postoperatively, with the difference being of statistical
      significance (P < .05). The complete surgical success rate of 3, 6, and 12 months
      after the operation was 85%, 75%, and 65%, respectively. Meanwhile, the qualified
      success rate of 3, 6, and 12 months after the operation was 85%, 80%, and 77.5%,
      respectively. The multivariate cox regression analysis showed that age (hazard
      ratio: 3.717, 7.246; 95% confidence interval: 1.149-12.048, 1.349-38.461; P =
      .028, .021) was influencing factors for complete success rate and qualified
      success rate among all NVG patients. Gender, previous operation history, primary
      disease, and preoperative IOP were found to be not significant.AGV implantation
      is an effective and safe surgical method to treat NVG. Age is an important factor
      influencing the surgical success rate.

PMID- 29049254
TI  - One-stage posterior approaches for treatment of thoracic spinal infection:
      Transforaminal and costotransversectomy, compared with anterior approach with
      posterior instrumentation.
AB  - Treating thoracic infective spondylodiscitis with anterior surgical approaches
      carry a relatively high risk of perioperative and postoperative complications.
      Posterior approaches have been reported to result in lower complication rates
      than anterior procedures, but more evidence is needed to demonstrate the safety
      and efficacy of 1-stage posterior approaches for treating infectious thoracic
      spondylodiscitis.Preoperative and postoperative clinical data, of 18 patients who
      underwent 2 types of 1-stage posterior procedures, costotransversectomy and
      transforaminal thoracic interbody debridement and fusion and 7 patients who
      underwent anterior debridement and reconstruction with posterior instrumentation,
      were retrospectively assessed.The clinical outcomes of patients treated with 1
      stage posterior approaches were generally good, with good infection control, back
      pain relief, kyphotic angle correction, and either partial or solid union for
      fusion status. Furthermore, they achieved shorter surgical time, fewer
      postoperative complications, and shorter hospital stay than the patients
      underwent anterior debridement with posterior instrumentation.The results
      suggested that treating thoracic spondylodiscitis with a single-stage posterior
      approach might prevent postoperative complications and avoid respiratory problems
      associated with anterior approaches. Single-stage posterior approaches would be
      recommended for thoracic spine infection, especially for patients with medical
      comorbidities.

PMID- 29049255
TI  - Necrotizing Soft Tissue Infections.

PMID- 29049256
TI  - Learning from Clinical Experience with Necrotizing Fasciitis: Treatment and
      Management.
AB  - GENERAL PURPOSE: To provide information about necrotizing fasciitis (NF), how to
      recognize it, and evidence-based treatment. TARGET AUDIENCE: This continuing
      education activity is intended for physicians, physician assistants, nurse
      practitioners, and nurses with an interest in skin and wound care. LEARNING
      OBJECTIVES/OUTCOMES: After completing this continuing education activity, you
      should be able to: ABSTRACT: Necrotizing fasciitis is a threatening, rapidly
      progressive, infectious disease of the soft tissue. In this article, based on 3
      cases, the authors aim to summarize the clinical experience of patients with
      necrotizing fasciitis and the current concepts of the treatment and management of
      this disease.

PMID- 29049258
TI  - Autologous Platelet-Rich Plasma/Thrombin Gel Combined with Split-Thickness Skin
      Graft to Manage Postinfectious Skin Defects: A Randomized Controlled Study.
AB  - BACKGROUND: Managing cutaneous substance loss after debridement is challenging,
      especially if it is secondary to necrotizing soft tissue infection, such as
      necrotizing fasciitis and Fournier gangrene. After skin graft reconstruction, the
      healing process is longer and may be difficult, depending on the wound site, skin
      defect size, and patient comorbidities. OBJECTIVE: The aim of this study was to
      investigate whether autologous platelet-rich plasma (A-PRP) could accelerate and
      improve wound healing after cutaneous reconstruction for tissue loss secondary to
      soft tissue infection. METHODS AND MATERIALS: A prospective, controlled,
      randomized, open-label study was conducted. Patients (N = 27) were randomized
      into 2 groups by drawing lots using sealed envelopes: an experimental (n = 14)
      and a control group (n = 13). Initially, all the necrotic tissue was extensively
      debrided and excised. In the experimental group, patients underwent a split
      thickness skin graft (STSG) combined with A-PRP/thrombin gel sprayed on the wound
      bed and on the STSG after staple fixation. In the control group, patients
      underwent an STSG alone. RESULTS: Results showed that the mean complete healing
      time was significantly reduced (by almost 50%) when A-PRP/thrombin gel was
      combined with an STSG compared with STSG alone (37.9 [SD, 14.3] days in the
      experimental group vs 73.7 [SD, 50.84] days in the control group, P = .01). No
      patient experienced complications during the follow-up period. CONCLUSION: The
      combination of A-PRP/thrombin gel and an STSG significantly improved clinical
      outcomes and shortened the wound healing time. Therefore, this treatment
      combination could provide a way to heal skin after a necrotizing soft tissue
      infection with minimal recovery time.

PMID- 29049257
TI  - Management of Moisture-Associated Skin Damage: A Scoping Review.
AB  - BACKGROUND: Protecting the skin against moisture-associated damage is an
      important component of comprehensive skin and wound care. Based on a review of
      literature, the authors propose key interventions to protect and prevent damage
      in the skin folds, perineum, and areas surrounding a wound or stoma. OBJECTIVE:
      The aim of this scoping review is to identify and provide a narrative integration
      of the existing evidence related to the management and prevention of moisture
      associated skin damage (MASD). METHODS: Study authors searched several databases
      for a broad spectrum of published and unpublished studies in English, published
      between 2000 and July 2015. Selected study information was collated in several
      different formats; ultimately, key findings were aggregated into a thematic
      description of the evidence to help generate a set of summative statements or
      recommendations. RESULTS: Based on inclusion criteria, 37 articles were
      considered appropriate for this review. Findings included functional definitions
      and prevalence rates of the 4 types of MASD, assessment scales for each, and 7
      evidence-based strategies for the management of MASD. CONCLUSIONS: Based on this
      scoping review of literature, the authors propose key interventions to protect
      and prevent MASD including the use of barrier ointments, liquid polymers, and
      cyanoacrylates to create a protective layer that simultaneously maintains
      hydration levels while blocking external moisture and irritants.

PMID- 29049259
TI  - The Association between Tinea Pedis and Feet-Washing Behavior in Patients with
      Diabetes: A Cross-sectional Study.
AB  - OBJECTIVES: To examine the correlations between elements of feet-washing
      behavior, presence of tinea pedis (TP), and patients' background characteristics
      in order to identify a concrete intervention method to prevent TP. DESIGN AND
      PARTICIPANTS: A cross-sectional study of 30 patients with diabetes (16 with TP)
      who were admitted to or visited the university hospital. MAIN OUTCOME MEASURES:
      The presence of TP was confirmed by the detection of dermatophytes by direct
      microscopy. Data on elements of feet-washing behavior, such as scrubbing between
      the toes, were collected by observing recorded videos of participants normally
      washing their feet as they do at home. The patients' background characteristics
      included demographic data; diabetes-related factors; patient knowledge regarding
      diabetes, foot problems, and TP prevention; purpose for feet washing; and any
      difficulties in feet washing. MAIN RESULTS: The number of times patients scrubbed
      between their toes while washing with soap was significantly lower in patients
      with TP (odds ratio, 0.95; P = .036; with a cutoff value of 35 times) and those
      who had difficulty in reaching their feet with their hands (B = -14.42, P =
      .041). CONCLUSIONS: An effective foot-washing protocol should include specific
      instructions for patients to scrub between their toes at least 35 times in all 8
      spaces while washing with soap. Appropriate advice is also needed for individuals
      who have difficulty reaching their feet with their hands. Education about
      appropriate foot-washing behavior may potentially prevent TP.

PMID- 29049261
TI  - APWCA 16th Annual National Clinical Conference Report.

PMID- 29049260
TI  - A Quantitative Analysis of Microcirculation in Skin Defects Covered with Topical
      Wound Dressings or a Newly Developed Collagen Matrix.
AB  - OBJECTIVE: Innovative skin substitutes and temporary wound dressings are
      frequently used in the treatment of superficial and partial-thickness wounds. The
      aim of this study was to compare 2 commonly used temporary skin dressings with a
      newly developed collagen matrix to determine changes in microcirculation as
      measured by blood flow, hemoglobin oxygenation, and relative hemoglobin values
      during healing of partial-thickness skin defects. METHODS: This animal study
      involved 28 adult male Lewis rats. On the back of each rat, 2 standardized
      partial-thickness skin defects were generated through a skin dermatome (n = 56).
      Then, wounds were treated with polylactide-based copolymer skin substitute
      (Suprathel, PolyMedics, Denkendorf, Germany; n = 14), biosynthetic skin dressing
      (Biobrane, Smith & Nephew, Hamburg, Germany; n = 14), or Collagen Cell Carrier
      (CCC; Naturin Viscofan, Weinheim, Germany; n = 14). The remaining control wounds
      were left untreated (n = 14). MAIN OUTCOME MEASURES: Perfusion dynamics were
      assessed every 10 days for 80 days with the O2C device (LEA Medizintechnik,
      Giebetaen, Germany) to determine blood flow, hemoglobin oxygenation, and relative
      amount of hemoglobin. MAIN RESULTS: Blood flow was increased in all wounds for at
      least 30 days after wound generation. The relative amounts of hemoglobin were
      increased in superficial layers (2 mm) for 10 to 20 days. Hemoglobin oxygenation
      in the superficial layers decreased in the polylactide-based copolymer skin
      substitute and biosynthetic skin dressing-treated groups and initially increased
      in the untreated wounds and CCC groups on day 10; these values also decreased.
      CONCLUSIONS: The presented results demonstrate the complex changes in
      microcirculation in the course of healing partial-thickness wounds with different
      wound dressings and contribute to a better understanding of these wounds.
      However, based on the results of the study, a clear recommendation for a specific
      substitute is not yet possible.

PMID- 29049262
TI  - Changing Misperceptions about Separate Billing for Disposable Negative Pressure
      Wound Therapy.

PMID- 29049263
TI  - Merit-Based Incentive Payment System: Referencing Source Documents.

PMID- 29049264
TI  - Learning from Clinical Experience with Necrotizing Fasciitis: Treatment and
      Management.

PMID- 29049265
TI  - Medical-Grade Honey Dressing Use in Developing Countries.
AB  - Compared with other medical honeys, SurgihoneyRO (H&R Healthcare Ltd, Southmoor,
      Abingdon, United Kingdom), a bioengineered medical-grade honey, delivers low
      concentrations of reactive oxygen to wounds over a sustained period. This article
      describes how one provider, Dr Jill Brooks, has successfully used this new
      antimicrobial dressing in Africa and examines the potential positive impact this
      dressing could have on wound care in developing countries.

PMID- 29049266
TI  - The Cost and Utility of Postreduction Radiographs After Closed Reduction of
      Pediatric Wrist and Forearm Fractures.
AB  - BACKGROUND: Formal radiographs are frequently obtained after reduction of closed
      pediatric wrist and forearm fracture performed under mini C-arm fluoroscopy.
      However, their utility has not been clearly demonstrated to justify the increased
      time, cost, and radiation exposure. We hypothesized that formal postreduction
      radiographs do not affect the rereduction rate of pediatric wrist and forearm
      fractures. We further sought to determine the time, monetary, and opportunity
      costs associated with obtaining these radiographs. METHODS: A total of 119
      patients presented to our urban, level I pediatric trauma center from April 2015
      to September 2015 with isolated, closed wrist and forearm fractures who underwent
      sedation and reduction using mini C-arm fluoroscopy. Demographic and injury
      variables were collected, along with incidence of rereduction and need for future
      surgery. Time intervals for sedation, awaiting x-ray, and total encounter periods
      were noted, and total direct and variable indirect costs for each encounter were
      obtained from our institution's cost accounting and billing databases. Marginal
      time and monetary costs were noted and further calculated as a percentage of the
      total encounter. Opportunity costs were calculated for the time spent obtaining
      the postreduction radiographs. RESULTS: Of 119 patients with isolated, closed
      wrist or forearm fractures, none required rereduction after initial reduction
      using sedation and mini C-arm fluoroscopy. Postreduction radiographs required an
      average of 26.2 minutes beyond the end of sedation, or 7.3% of the encounter time
      and cost. The direct cost of the x-ray was 2.6% of the encounter cost. With our
      institution's annual volume, this time could have been used to see an additional
      656 patients per year. CONCLUSIONS: Postreduction formal radiographs did not
      result in changes in management. There are significant direct and opportunity
      costs for each patient who undergoes additional formal radiographs. Pediatric
      patients with isolated, closed wrist or forearm fractures do not routinely need
      formal radiographs after reduction under mini C-arm fluoroscopy. LEVEL OF
      EVIDENCE: Level IV-Therapeutic.

PMID- 29049267
TI  - Variation Among Pediatric Orthopaedic Surgeons When Treating Medial Epicondyle
      Fractures.
AB  - BACKGROUND: Medial epicondyle fractures are a common pediatric and adolescent
      injury accounting for 11% to 20% of elbow fractures in this population. This
      purpose of this study was to determine the variability among pediatric
      orthopaedic surgeons when treating pediatric medial epicondyle fractures.
      METHODS: A discrete choice experiment was conducted to determine which patient
      and injury attributes influence the management of medial epicondyle fractures by
      pediatric orthopaedic surgeons. A convenience sample of 13 pediatric orthopaedic
      surgeons reviewed 60 case vignettes of medial epicondyle fractures that included
      elbow radiographs and patient/injury characteristics. Displacement was
      incorporated into the study model as a fixed effect. Surgeons were queried if
      they would treat the injury with immobilization alone or open reduction and
      internal fixation (ORIF). Statistical analysis was performed using a mixed effect
      regression model. In addition, surgeons filled out a demographic questionnaire
      and a risk assessment to determine if these factors affected clinical decision
      making. RESULTS: Elbow dislocation and fracture displacement were the only
      attributes that significantly influenced surgeons to perform surgery (P<0.05).
      The presence of an elbow dislocation had the largest impact on surgeons when
      choosing operative care (beta=-0.14; P=0.02). In addition, for every 1 mm
      increase in displacement, surgeons tended to favor ORIF by a factor of 0.09
      (P<0.01). Sex, mechanism of injury, and sport participation did not influence
      decision-making. In total, 54% of the surgeons demonstrated a preference for ORIF
      for the included scenarios. On the basis of the personality Likert scale,
      participants were neither high-risk takers nor extremely risk adverse with an
      average-risk score of 2.24. Participant demographics did not influence decision
      making. CONCLUSIONS: There is substantial variation among pediatric orthopaedic
      surgeons when treating medial epicondyle fractures. The decision to operate is
      significantly based on the degree of fracture displacement and if there is a
      concomitant elbow dislocation. There is no standardization regarding how to treat
      medial epicondyle fractures and better treatment algorithms are needed to provide
      better patient outcomes. LEVEL OF EVIDENCE: Level V.

PMID- 29049268
TI  - Patient and Parent Satisfaction With Sling Use After Pediatric Upper Extremity
      Fractures: A Randomized Controlled Trial of a Customized Cast-sling Versus
      Standard Cast and Sling.
AB  - BACKGROUND: Long arm cast immobilization after operative and nonoperative
      treatment of pediatric upper extremity fractures is common. The use of a sling to
      aid in carrying the casted extremity as well as provide further immobilization is
      also common practice. Off-the-shelf slings vary in quality and fit, can be
      confusing for parents/patients to apply, and lead to frustration and
      dissatisfaction with its use. The purpose of this investigation was to compare
      patient/parent centered outcomes after the use of a customized sling compared
      with a standard sling by utilizing a prospective, randomized-controlled trial. We
      hypothesized that patients and their parents would find the "Providence" Pedi
      Cast-Sling (PPCS) to be more convenient and be more satisfied with its use
      compare with a standard sling. METHODS: Eligible subjects included patients 0 to
      18 years old, evaluated at an urban, tertiary care pediatric emergency department
      (ED), who sustained an upper extremity fracture that required placement of a long
      arm cast. Exclusion criteria were: open fractures; fractures at multiple levels;
      fractures requiring urgent/emergent surgery; admitted patients; bivalved casts.
      Patients were randomized to receive a standard sling or a PPCS. Questionnaires
      assessing patient/parent satisfaction, preferences, sling-use, and pain level
      were collected at patients' first follow-up visit. RESULTS: A total of 100
      patients were randomized with 71 questionnaires available for analysis (39
      standard sling vs. 32 PPCS). There were statistically significant differences for
      satisfaction scores for all related questions between patients who received a
      PPCS compared with a standard sling. Patients and their parents were more likely
      to choose the PPCS (P=0.001), were more satisfied with the PPCS (P<0.006), and
      reported the PPCS to be more convenient than a standard sling (P<0.001). Patients
      who received a PPCS wore the sling for a greater number of hours during the day
      (10.3+/-7.1 h) compared with those who received a standard sling (5.9+/-5.0 h)
      (P=0.004). CONCLUSIONS: The "Providence" Pedi Cast-Sling is a superior
      alternative to an off-the-shelf sling when used after the application of a long
      arm cast providing greater convenience, compliance, and satisfaction to both
      patients and families. LEVEL OF EVIDENCE: Level I-Prospective randomized
      controlled trial.

PMID- 29049269
TI  - Long-term Surgical Outcomes After Early Definitive Spinal Fusion for Early-onset
      Scoliosis With Neurofibromatosis Type 1 at Mean Follow-up of 14 Years.
AB  - BACKGROUND: Several authors mentioned surgical outcome for scoliosis associated
      with neurofibromatosis type 1 (NF-1). However, no studies have summarized long
      term surgical outcomes after surgical treatment of early-onset scoliosis (EOS)
      with NF-1. The purpose of this study is to evaluate the long-term surgical
      outcome after early definitive spinal fusion for EOS in NF-1 patients. METHODS:
      We performed a retrospective review on a cohort of 11 patients diagnosed with EOS
      associated with NF-1 between 1990 and 2009 in our hospital. The study included 7
      male and 4 female NF-1 patients with a mean age at fusion surgery of 8 years 4
      months who underwent early definitive spinal fusion for EOS. We reviewed
      radiographs, computed tomography and magnetic resonance images for each patient.
      The data collected included type of NF-1, Cobb angles, kyphotic angle, spinal
      length (T1-S1), and pulmonary function. We also evaluated progression of the
      dystrophic change through radiographs and computed tomography during the follow
      up period. RESULTS: The mean follow-up duration was 14 years (5 y 10 mo to 25 y).
      All patients underwent anterior and posterior fusion surgeries in either 1 or 2
      stages. Seven cases had subtotal tumor resection from the concave side followed
      by rib strut grafting. The mean preoperative Cobb angle of the primary curve was
      corrected from 71.2 to 24.1 degrees and was maintained at the final follow-up at
      23.5 degrees. Mean values for preoperative and final follow-up T1-S1 heights were
      30.7 and 36.2 cm, respectively. Mean values for preoperative and final follow-up
      % forced vital capacity (the present/the predicted) were 75.0% and 74.4%,
      respectively. The dystrophic change progressed in all cases during the long-term
      follow-up. CONCLUSIONS: Our goals for NF-1 scoliosis are to obtain deformity
      correction, to achieve stable instrumentation by using longer fusion levels and
      to attain a solid fusion mass that can tolerate continual erosion during the long
      term follow-up. We achieve this by using a circumferential approach for EOS
      associated with NF-1. LEVEL OF EVIDENCE: Level IV-case series.

PMID- 29049271
TI  - Announcement: Community Preventive Services Task Force Recommendation for
      Comprehensive Telehealth Methods to Deliver Dietary Interventions for Chronic
      Disease Management.

PMID- 29049272
TI  - QuickStats: Infant Mortality Rate, by Urbanization Level* - National Vital
      Statistics System, United States, 2007 and 2015.
AB  - In both 2007 and 2015, infant mortality rates were highest in rural counties (7.5
      infant deaths per 1,000 live births and 6.8, respectively). Rates were lower in
      small and medium urban counties (7.1 in 2007 and 6.4 in 2015) and lowest in large
      urban counties (6.4 in 2007 and 5.4 in 2015). For all three urbanization levels,
      infant mortality rates were significantly lower in 2015, compared with rates in
      2007.

PMID- 29049270
TI  - Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity.
AB  - : BACKGROUND The fast pace of life, promoting fast food consumption and low
      physical activity, has resulted in obesity and/or diabetes as being serious
      social problems. The aim of the present study was to evaluate concentrations of
      selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess
      the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in
      relation to degree of obesity. MATERIAL AND METHODS The study comprised 92 T2D
      subjects divided into 4 groups according to BMI value - I (normal body weight),
      II (overweight), III (obesity), and IV (severe obesity) - and 20 healthy
      volunteers (control group). Each group was divided into male and female
      subgroups. Plasma concentrations of adipokines were determined by enzyme-linked
      immunosorbent assay. RESULTS In women, leptin concentration was significantly
      higher in group IV, whereas in men it was higher in groups III and IV than in the
      control group and groups I and II. Irrespective of sex, a significant decrease in
      adiponectin level was observed in group III vs. CONTROL: There was no significant
      difference in resistin levels. In women visfatin was markedly enhanced in group
      III, whereas in men in groups II, III and IV vs. CONTROL: Leptin/adiponectin
      ratio was increased in groups III and IV vs. control in women, whereas in men vs.
      both control and group I. CONCLUSIONS The obese type 2 diabetic patients
      presented a disturbed adipokine profile, which seems to be an important link
      between obesity and T2D. The future studies concerning the question if regulating
      of adipokines' concentrations could be a promising approach for managing
      metabolic disorders seem to be well-grounded.

PMID- 29049273
TI  - Tdap Vaccination Coverage During Pregnancy - Selected Sites, United States, 2006
      2015.
AB  - Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine
      is recommended during the third trimester of each pregnancy to provide protection
      to newborns, who are at risk for pertussis-related morbidity and mortality (1).
      As part of its case-control surveillance study of medications and birth defects,
      the Birth Defects Study of the Slone Epidemiology Center at Boston University
      (the Birth Defects Study) has recorded data on vaccinations received during
      pregnancy since 2006. Among 5,606 mothers of infants without structural birth
      defects in this population (control group), <1% had received Tdap vaccine before
      2009. By 2012, the percentage of mothers of infants in the control group (control
      infants) who had received Tdap increased to approximately 9%, and then in 2013
      and continuing through 2015, increased markedly, to 28% and 54%, respectively. As
      the prevalence of maternal Tdap vaccination increased, so did the proportion of
      pregnant women who received Tdap in the third trimester, as recommended (94%-100%
      from 2010 to 2015). The vast majority of Tdap vaccinations (96%) were received in
      a traditional health care setting (e.g., the office of the woman's obstetrician
      or primary care physician or her prenatal clinic). Increasing vaccination
      coverage during pregnancy could help reduce the impact of pertussis on infant
      morbidity and mortality.

PMID- 29049275
TI  - Notes from the Field: Counterfeit Percocet-Related Overdose Cluster - Georgia,
      June 2017.

PMID- 29049274
TI  - Reporting Deaths Among Children Aged <5 Years After the Ebola Virus Disease
      Epidemic - Bombali District, Sierra Leone, 2015-2016.
AB  - Mortality surveillance and vital registration are limited in Sierra Leone, a
      country with one of the highest mortality rates among children aged <5 years
      worldwide, approximately 120 deaths per 1,000 live births (1,2). To inform
      efforts to strengthen surveillance, stillbirths and deaths in children aged <5
      years from multiple surveillance streams in Bombali Sebora chiefdom were
      retrospectively reviewed. In total, during January 2015-November 2016, 930 deaths
      in children aged <5 years were identified, representing 73.3% of the 1,269 deaths
      that were expected based on modeled estimates. The "117" telephone alert system
      established during the Ebola virus disease (Ebola) epidemic captured 683 (73.4%)
      of all reported deaths in children aged <5 years, and was the predominant
      reporting source for stillbirths (n = 172). In the absence of complete vital
      events registration, 117 call alerts markedly improved the completeness of
      reporting of stillbirths and deaths in children aged <5 years.

PMID- 29049276
TI  - HIV Testing, Linkage to HIV Medical Care, and Interviews for Partner Services
      Among Women - 61 Health Department Jurisdictions, United States, Puerto Rico, and
      the U.S. Virgin Islands, 2015.
AB  - Diagnoses of human immunodeficiency virus (HIV) infection among women declined
      17% during 2011-2015, and a total of 7,498 women received a diagnosis of HIV
      infection in 2015 (1). Although black or African American (black) women accounted
      for only 12% of the U.S. female population, 60% of women with newly diagnosed HIV
      infection were black (1,2). By the end of 2014, an estimated 255,900 women were
      living with HIV infection (3), including approximately 12% who did not know they
      were infected; in addition, approximately 45% of women who had received a
      diagnosis had not achieved viral suppression (3). HIV testing is an important
      public health strategy for identifying women with HIV infection and linking them
      to HIV medical care. Analysis of CDC-funded program data submitted by 61 health
      departments in 2015 indicated that among 4,749 women tested who received a
      diagnosis of HIV infection, 2,951 (62%) had received a diagnosis in the past
      (previous diagnosis), and 1,798 (38%) were receiving a diagnosis for the first
      time (new diagnosis). Of those who had received a previous diagnosis, 87% were
      not in HIV medical care at the time of the current test. Testing and identifying
      women who are living with HIV infection but who are not in care (regardless of
      when they received their first diagnosis) and rapidly linking them to care so
      they can receive antiretroviral therapy and become virally suppressed are
      essential for reducing HIV infection among all women.

PMID- 29049278
TI  - Illicit Drug Use, Illicit Drug Use Disorders, and Drug Overdose Deaths in
      Metropolitan and Nonmetropolitan Areas - United States.
AB  - PROBLEM/CONDITION: Drug overdoses are a leading cause of injury death in the
      United States, resulting in approximately 52,000 deaths in 2015. Understanding
      differences in illicit drug use, illicit drug use disorders, and overall drug
      overdose deaths in metropolitan and nonmetropolitan areas is important for
      informing public health programs, interventions, and policies. REPORTING PERIOD:
      Illicit drug use and drug use disorders during 2003-2014, and drug overdose
      deaths during 1999-2015. DESCRIPTION OF DATA: The National Survey of Drug Use and
      Health (NSDUH) collects information through face-to-face household interviews
      about the use of illicit drugs, alcohol, and tobacco among the U.S.
      noninstitutionalized civilian population aged >=12 years. Respondents include
      residents of households and noninstitutional group quarters (e.g., shelters,
      rooming houses, dormitories, migratory workers' camps, and halfway houses) and
      civilians living on military bases. NSDUH variables include sex, age,
      race/ethnicity, residence (metropolitan/nonmetropolitan), annual household
      income, self-reported drug use, and drug use disorders. National Vital Statistics
      System Mortality (NVSS-M) data for U.S. residents include information from death
      certificates filed in the 50 states and the District of Columbia. Cases were
      selected with an underlying cause of death based on the ICD-10 codes for drug
      overdoses (X40-X44, X60-X64, X85, and Y10-Y14). NVSS-M variables include decedent
      characteristics (sex, age, and race/ethnicity) and information on intent
      (unintentional, suicide, homicide, or undetermined), location of death (medical
      facility, in a home, or other [including nursing homes, hospices, unknown, and
      other locations]) and county of residence (metropolitan/nonmetropolitan).
      Metropolitan/nonmetropolitan status is assigned independently in each data
      system. NSDUH uses a three-category system: Core Based Statistical Area (CBSA) of
      >=1 million persons; CBSA of <1 million persons; and not a CBSA, which for
      simplicity were labeled large metropolitan, small metropolitan, and
      nonmetropolitan. Deaths from NVSS-M are categorized by the county of residence of
      the decedent using CDC's National Center for Health Statistics 2013 Urban-Rural
      Classification Scheme, collapsed into two categories (metropolitan and
      nonmetropolitan). RESULTS: Although both metropolitan and nonmetropolitan areas
      experienced significant increases from 2003-2005 to 2012-2014 in self-reported
      past-month use of illicit drugs, the prevalence was highest for the large
      metropolitan areas compared with small metropolitan or nonmetropolitan areas
      throughout the study period. Notably, past-month use of illicit drugs declined
      over the study period for the youngest respondents (aged 12-17 years). The
      prevalence of past-year illicit drug use disorders among persons using illicit
      drugs in the past year varied by metropolitan/nonmetropolitan status and changed
      over time. Across both metropolitan and nonmetropolitan areas, the prevalence of
      past-year illicit drug use disorders declined during 2003-2014. In 2015,
      approximately six times as many drug overdose deaths occurred in metropolitan
      areas than occurred in nonmetropolitan areas (metropolitan: 45,059;
      nonmetropolitan: 7,345). Drug overdose death rates (per 100,000 population) for
      metropolitan areas were higher than in nonmetropolitan areas in 1999 (6.4 versus
      4.0), however, the rates converged in 2004, and by 2015, the nonmetropolitan rate
      (17.0) was slightly higher than the metropolitan rate (16.2). INTERPRETATION:
      Drug use and subsequent overdoses continue to be a critical and complicated
      public health challenge across metropolitan/nonmetropolitan areas. The decline in
      illicit drug use by youth and the lower prevalence of illicit drug use disorders
      in rural areas during 2012-2014 are encouraging signs. However, the increasing
      rate of drug overdose deaths in rural areas, which surpassed rates in urban
      areas, is cause for concern. PUBLIC HEALTH ACTIONS: Understanding the differences
      between metropolitan and nonmetropolitan areas in drug use, drug use disorders,
      and drug overdose deaths can help public health professionals to identify,
      monitor, and prioritize responses. Consideration of where persons live and where
      they die from overdose could enhance specific overdose prevention interventions,
      such as training on naloxone administration or rescue breathing. Educating
      prescribers on CDC's guideline for prescribing opioids for chronic pain (Dowell
      D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain
      United States, 2016. MMWR Recomm Rep 2016;66[No. RR-1]) and facilitating better
      access to medication-assisted treatment with methadone, buprenorphine, or
      naltrexone could benefit communities with high opioid use disorder rates.

PMID- 29049279
TI  - Knowledge, Attitudes, and Practices Related to Ebola Virus Disease at the End of
      a National Epidemic - Guinea, August 2015.
AB  - Health communication and social mobilization efforts to improve the public's
      knowledge, attitudes, and practices (KAP) regarding Ebola virus disease (Ebola)
      were important in controlling the 2014-2016 Ebola epidemic in Guinea (1), which
      resulted in 3,814 reported Ebola cases and 2,544 deaths.* Most Ebola cases in
      Guinea resulted from the washing and touching of persons and corpses infected
      with Ebola without adequate infection control precautions at home, at funerals,
      and in health facilities (2,3). As the 18-month epidemic waned in August 2015,
      Ebola KAP were assessed in a survey among residents of Guinea recruited through
      multistage cluster sampling procedures in the nation's eight administrative
      regions (Boke, Conakry, Faranah, Kankan, Kindia, Labe, Mamou, and Nzerekore).
      Nearly all participants (92%) were aware of Ebola prevention measures, but 27%
      believed that Ebola could be transmitted by ambient air, and 49% believed they
      could protect themselves from Ebola by avoiding mosquito bites. Of the
      participants, 95% reported taking actions to avoid getting Ebola, especially more
      frequent handwashing (93%). Nearly all participants (91%) indicated they would
      send relatives with suspected Ebola to Ebola treatment centers, and 89% said they
      would engage special Ebola burial teams to remove corpses with suspected Ebola
      from homes. Of the participants, 66% said they would prefer to observe an Ebola
      affected corpse from a safe distance at burials rather than practice traditional
      funeral rites involving corpse contact. The findings were used to guide the
      ongoing epidemic response and recovery efforts, including health communication,
      social mobilization, and planning, to prevent and respond to future outbreaks or
      sporadic cases of Ebola.

PMID- 29049277
TI  - Update: Interim Guidance for the Diagnosis, Evaluation, and Management of Infants
      with Possible Congenital Zika Virus Infection - United States, October 2017.
AB  - CDC has updated its interim guidance for U.S. health care providers caring for
      infants with possible congenital Zika virus infection (1) in response to recently
      published updated guidance for health care providers caring for pregnant women
      with possible Zika virus exposure (2), unknown sensitivity and specificity of
      currently available diagnostic tests for congenital Zika virus infection, and
      recognition of additional clinical findings associated with congenital Zika virus
      infection. All infants born to mothers with possible Zika virus exposure* during
      pregnancy should receive a standard evaluation at birth and at each subsequent
      well-child visit including a comprehensive physical examination, age-appropriate
      vision screening and developmental monitoring and screening using validated tools
      (3-5), and newborn hearing screen at birth, preferably using auditory brainstem
      response (ABR) methodology (6). Specific guidance for laboratory testing and
      clinical evaluation are provided for three clinical scenarios in the setting of
      possible maternal Zika virus exposure: 1) infants with clinical findings
      consistent with congenital Zika syndrome regardless of maternal testing results,
      2) infants without clinical findings consistent with congenital Zika syndrome who
      were born to mothers with laboratory evidence of possible Zika virus infection,?
      and 3) infants without clinical findings consistent with congenital Zika syndrome
      who were born to mothers without laboratory evidence of possible Zika virus
      infection. Infants in the first two scenarios should receive further testing and
      evaluation for Zika virus, whereas for the third group, further testing and
      clinical evaluation for Zika virus are not recommended. Health care providers
      should remain alert for abnormal findings (e.g., postnatal-onset microcephaly and
      eye abnormalities without microcephaly) in infants with possible congenital Zika
      virus exposure without apparent abnormalities at birth.

PMID- 29049280
TI  - Ethoscopes: An open platform for high-throughput ethomics.
AB  - Here, we present the use of ethoscopes, which are machines for high-throughput
      analysis of behavior in Drosophila and other animals. Ethoscopes provide a
      software and hardware solution that is reproducible and easily scalable. They
      perform, in real-time, tracking and profiling of behavior by using a supervised
      machine learning algorithm, are able to deliver behaviorally triggered stimuli to
      flies in a feedback-loop mode, and are highly customizable and open source.
      Ethoscopes can be built easily by using 3D printing technology and rely on
      Raspberry Pi microcomputers and Arduino boards to provide affordable and flexible
      hardware. All software and construction specifications are available at
      http://lab.gilest.ro/ethoscope.

PMID- 29049281
TI  - Unmet needs for analyzing biological big data: A survey of 704 NSF principal
      investigators.
AB  - In a 2016 survey of 704 National Science Foundation (NSF) Biological Sciences
      Directorate principal investigators (BIO PIs), nearly 90% indicated they are
      currently or will soon be analyzing large data sets. BIO PIs considered a range
      of computational needs important to their work, including high performance
      computing (HPC), bioinformatics support, multistep workflows, updated analysis
      software, and the ability to store, share, and publish data. Previous studies in
      the United States and Canada emphasized infrastructure needs. However, BIO PIs
      said the most pressing unmet needs are training in data integration, data
      management, and scaling analyses for HPC-acknowledging that data science skills
      will be required to build a deeper understanding of life. This portends a growing
      data knowledge gap in biology and challenges institutions and funding agencies to
      redouble their support for computational training in biology.

PMID- 29049282
TI  - Behavioral intervention to reduce opioid overdose among high-risk persons with
      opioid use disorder: A pilot randomized controlled trial.
AB  - OBJECTIVE: The United States is amidst an opioid epidemic, including synthetic
      opioids that may result in rapid death, leaving minimal opportunity for bystander
      rescue. We pilot tested a behavioral intervention to reduce the occurrence of
      opioid overdose among opioid dependent persons at high-risk for subsequent
      overdose. MATERIALS AND METHODS: We conducted a single-blinded randomized
      controlled trial of a repeated dose motivational interviewing intervention
      (REBOOT) to reduce overdose versus treatment as usual, defined as information and
      referrals, over 16 months at the San Francisco Department of Public Health from
      2014-2016. Participants were 18-65 years of age, had opioid use disorder by
      Structured Clinical Interview, active opioid use, opioid overdose within 5 years,
      and prior receipt of naloxone kits. The intervention was administered at months
      0, 4, 8, and 12, preceded by the assessment which was also administered at month
      16. Dual primary outcomes were any overdose event and number of events, collected
      by computer-assisted personal interview, as well as any fatal overdose events per
      vital records. RESULTS: A total of 78 persons were screened and 63 enrolled. Mean
      age was 43 years, 67% were born male, 65% White, 17% African-American, and 14%
      Latino. Ninety-two percent of visits and 93% of counseling sessions were
      completed. At baseline, 33.3% of participants had experienced an overdose in the
      past four months, with a similar mean number of overdoses in both arms (p =
      0.95); 29% overdosed during follow-up. By intention-to-treat, participants
      assigned to REBOOT were less likely to experience any overdose (incidence rate
      ratio [IRR] 0.62 [95%CI 0.41-0.92, p = 0.019) and experienced fewer overdose
      events (IRR 0.46, 95%CI 0.24-0.90, p = 0.023), findings that were robust to
      sensitivity analyses. There were no differences between arms in days of opioid
      use, substance use treatment, or naloxone carriage. CONCLUSIONS: REBOOT reduced
      the occurrence of any opioid overdose and the number of overdoses. TRIAL
      REGISTRATION: clinicaltrials.gov NCT02093559.

PMID- 29049283
TI  - The impact of muscle relaxation techniques on the quality of life of cancer
      patients, as measured by the FACT-G questionnaire.
AB  - INTRODUCTION: Patients with cancer frequently suffer from emotional distress,
      characterized by psychological symptoms such as anxiety or depression. The
      presence of psychological symptoms combined with the complex nature of oncology
      processes can negatively impact patients' quality of life. We aimed to determine
      the impact of a relaxation protocol on improving quality of life in a sample of
      oncological patients treated in the Spanish National Public Health System.
      MATERIALS AND METHODS: We conducted a multicenter interventional study without a
      control group. In total, 272 patients with different oncologic pathologies and
      showing symptoms of anxiety were recruited from 10 Spanish public hospitals. The
      intervention comprised abbreviated progressive muscle relaxation training,
      according to Bernstein and Borkovec. This was followed by weekly telephone calls
      to each patient over a 1-month period. We collected sociodemographic variables
      related to the disease process, including information about mental health and the
      intervention. Patients' quality of life was assessed using the Functional
      Assessment of Cancer Therapy-General (FACT-G) questionnaire. Bivariate and
      univariate analyses were performed, along with an analysis of multiple
      correspondences to identify subgroups of patients with similar variations on the
      FACT-G. RESULTS: Patients showed statistically significant improvements on the
      FACT-G overall score (W = 16806; p<0.001), with an initial mean score of 55.33+/
      10.42 and a final mean score of 64.49+/-7.70. We also found significant
      improvements for all subscales: emotional wellbeing (W = 13118; p<0.001),
      functional wellbeing (W = 16155.5; p<0.001), physical wellbeing (W = 8885.5;
      p<0.001), and social and family context (W = -1840; p = 0.037). CONCLUSIONS:
      Patients with cancer who learned and practiced abbreviated progressive muscle
      relaxation experienced improvement in their perceived quality of life as measured
      by the FACT-G. Our findings support a previous assumption that complementary
      techniques (including relaxation techniques) are effective in improving the
      quality of life of patients with cancer.

PMID- 29049284
TI  - Learning infectious disease epidemiology in a modern framework.

PMID- 29049285
TI  - 2009-2010 Influenza A(H1N1)-related critical illness among Aboriginal and non
      Aboriginal Canadians.
AB  - BACKGROUND: Preliminary studies suggested that Aboriginal Canadians had
      disproportionately higher rates of infection, hospitalization, and critical
      illness due to pandemic Influenza A(H1N1)pdm09. METHODS: We used a prospective
      cohort study of critically ill patients with laboratory confirmed or probable
      H1N1 infection in Canada between April 16 2009 and April 12 2010. Baseline
      characteristics, medical interventions, clinical course and outcomes were
      compared between Aboriginal and non-Aboriginal patients. The primary outcome was
      hospital mortality. RESULTS: Of 647 critically ill adult patients with known
      ethnicity, 81 (12.5%) were Aboriginal, 566 (87.5%) were non-Aboriginal.
      Aboriginal patients were younger (mean [SD] age 40.7[13.7] v. 49.0[14.9] years, p
      < 0.001) and more frequently female (64.2% v. 51.1%, p = 0.027). Rates of any co
      morbid illnesses (Aboriginal v. non-Aboriginal, 92.6% v. 91.0%, p = 0.63), time
      from symptom onset to hospital admission (median [interquartile range] 4 [2-7] v.
      4 [2-7] days, p = 0.84), time to ICU admission (5 [3-8] v.5 [3-8] days, p =
      0.91), and severity of illness (mean APACHE II score (19.9 [9.6] v. 21.1 [9.9], p
      = 0.33) were similar. A similar proportion of Aboriginal patients received
      antiviral medication before ICU admission than non-Aboriginal patients (91.4% v.
      93.8%, p = 0.40). Among Aboriginal versus non-Aboriginal patients, the need for
      mechanical ventilation (93.8% v. 88.6%, p = 0.15), ventilator-free days (14 [3
      23] v. 17 [0-24], p = 0.62), durations of stay in ICU (13[7-19.5] v. 11 [5-8]
      days, p = 0.05), hospital (19 [12.5-33.5] v. 18 [11-35] days, p = 0.63), and
      hospital mortality were similar (19.8% v. 22.6%, p = 0.56). In multiple logistic
      regression analyses, higher APACHE II score (1.06; 1.04-1.09, p<0.001) was
      independently associated with an increased risk of death; antiviral treatment
      with a lower risk of death (0.34; 0.15 - 0.78, p = 0.01). Ethnicity was not
      associated with mortality. INTERPRETATION: During the 2009-2010 Influenza A
      (H1N1) pandemic, Aboriginal and non-Aboriginal Canadians with H1N1-related
      critical illness had a similar risk of death, after adjusting for potential
      confounding factors.

PMID- 29049286
TI  - DenvInt: A database of protein-protein interactions between dengue virus and its
      hosts.

PMID- 29049287
TI  - BBSome function is required for both the morphogenesis and maintenance of the
      photoreceptor outer segment.
AB  - Genetic mutations disrupting the structure and function of primary cilia cause
      various inherited retinal diseases in humans. Bardet-Biedl syndrome (BBS) is a
      genetically heterogeneous, pleiotropic ciliopathy characterized by retinal
      degeneration, obesity, postaxial polydactyly, intellectual disability, and
      genital and renal abnormalities. To gain insight into the mechanisms of retinal
      degeneration in BBS, we developed a congenital knockout mouse of Bbs8, as well as
      conditional mouse models in which function of the BBSome (a protein complex that
      mediates ciliary trafficking) can be temporally inactivated or restored. We
      demonstrate that BBS mutant mice have defects in retinal outer segment
      morphogenesis. We further demonstrate that removal of Bbs8 in adult mice affects
      photoreceptor function and disrupts the structural integrity of the outer
      segment. Notably, using a mouse model in which a gene trap inhibiting Bbs8 gene
      expression can be removed by an inducible FLP recombinase, we show that when BBS8
      is restored in immature retinas with malformed outer segments, outer segment
      extension can resume normally and malformed outer segment discs are displaced
      distally by normal outer segment structures. Over time, the retinas of the
      rescued mice become morphologically and functionally normal, indicating that
      there is a window of plasticity when initial retinal outer segment morphogenesis
      defects can be ameliorated.

PMID- 29049288
TI  - Seasonality in risk of pandemic influenza emergence.
AB  - Influenza pandemics can emerge unexpectedly and wreak global devastation.
      However, each of the six pandemics since 1889 emerged in the Northern Hemisphere
      just after the flu season, suggesting that pandemic timing may be predictable.
      Using a stochastic model fit to seasonal flu surveillance data from the United
      States, we find that seasonal flu leaves a transient wake of heterosubtypic
      immunity that impedes the emergence of novel flu viruses. This refractory period
      provides a simple explanation for not only the spring-summer timing of historical
      pandemics, but also early increases in pandemic severity and multiple waves of
      transmission. Thus, pandemic risk may be seasonal and predictable, with the
      accuracy of pre-pandemic and real-time risk assessments hinging on reliable
      seasonal influenza surveillance and precise estimates of the breadth and duration
      of heterosubtypic immunity.

PMID- 29049290
TI  - Quality control processes in allografting: A twenty-year retrospective review of
      a hospital-based bone bank in Taiwan.
AB  - Musculoskeletal allografts are now commonly used. To decrease the potential risks
      of transmission of pathogenic bacteria, fungi, or viruses to the transplant
      recipients, certain issues regarding the management of patients who receive
      contaminated allografts need to be addressed. We aimed to clarify the incidence
      and extent of disease transmission from allografts by analyzing the allografting
      procedures performed in the bone bank of our hospital over the past 20 years. We
      retrospectively reviewed the data from our allograft registry center on 3979
      allografts that were implanted in 3193 recipients throughout a period of two
      decades, from July 1991 to June 2011. The source of the allografts, results of
      all screening tests, dates of harvesting and implantation, and recipients of all
      allografts were checked. With the help of the Center for Infection Control of our
      hospital, a strict prospective, hospital-wide, on-site surveillance was
      conducted, and every patient with healthcare-associated infection was identified.
      Fisher's exact test was used to compare the infection rate between recipients
      with sterile allografts and those with contaminated allografts. The overall
      discard and infection rates were, respectively, 23% and 1.3% in the first decade
      (1991-2001); and 18.4% and 1.25% in the second decade (2001-2011). The infection
      rate of contaminated allograft recipients was significantly higher than that of
      sterile allograft recipients (10% vs. 1.15%, P < 0.01) in the second decade. Both
      infection and discard rates of our bone bank are comparable with those of
      international bone banks. Strict allograft processing and adequate prophylactic
      use of antibiotics are critical to prevent infection and disease transmission in
      such cases.

PMID- 29049289
TI  - A molecular atlas of the developing ectoderm defines neural, neural crest,
      placode, and nonneural progenitor identity in vertebrates.
AB  - During vertebrate neurulation, the embryonic ectoderm is patterned into lineage
      progenitors for neural plate, neural crest, placodes and epidermis. Here, we use
      Xenopus laevis embryos to analyze the spatial and temporal transcriptome of
      distinct ectodermal domains in the course of neurulation, during the
      establishment of cell lineages. In order to define the transcriptome of small
      groups of cells from a single germ layer and to retain spatial information,
      dorsal and ventral ectoderm was subdivided along the anterior-posterior and
      medial-lateral axes by microdissections. Principal component analysis on the
      transcriptomes of these ectoderm fragments primarily identifies embryonic axes
      and temporal dynamics. This provides a genetic code to define positional
      information of any ectoderm sample along the anterior-posterior and dorsal
      ventral axes directly from its transcriptome. In parallel, we use nonnegative
      matrix factorization to predict enhanced gene expression maps onto early and mid
      neurula embryos, and specific signatures for each ectoderm area. The clustering
      of spatial and temporal datasets allowed detection of multiple biologically
      relevant groups (e.g., Wnt signaling, neural crest development, sensory placode
      specification, ciliogenesis, germ layer specification). We provide an interactive
      network interface, EctoMap, for exploring synexpression relationships among genes
      expressed in the neurula, and suggest several strategies to use this
      comprehensive dataset to address questions in developmental biology as well as
      stem cell or cancer research.

PMID- 29049291
TI  - A deep convolutional neural network for classification of red blood cells in
      sickle cell anemia.
AB  - Sickle cell disease (SCD) is a hematological disorder leading to blood vessel
      occlusion accompanied by painful episodes and even death. Red blood cells (RBCs)
      of SCD patients have diverse shapes that reveal important biomechanical and bio
      rheological characteristics, e.g. their density, fragility, adhesive properties,
      etc. Hence, having an objective and effective way of RBC shape quantification and
      classification will lead to better insights and eventual better prognosis of the
      disease. To this end, we have developed an automated, high-throughput, ex-vivo
      RBC shape classification framework that consists of three stages. First, we
      present an automatic hierarchical RBC extraction method to detect the RBC region
      (ROI) from the background, and then separate touching RBCs in the ROI images by
      applying an improved random walk method based on automatic seed generation.
      Second, we apply a mask-based RBC patch-size normalization method to normalize
      the variant size of segmented single RBC patches into uniform size. Third, we
      employ deep convolutional neural networks (CNNs) to realize RBC classification;
      the alternating convolution and pooling operations can deal with non-linear and
      complex patterns. Furthermore, we investigate the specific shape factor
      quantification for the classified RBC image data in order to develop a general
      multiscale shape analysis. We perform several experiments on raw microscopy image
      datasets from 8 SCD patients (over 7,000 single RBC images) through a 5-fold
      cross validation method both for oxygenated and deoxygenated RBCs. We demonstrate
      that the proposed framework can successfully classify sickle shape RBCs in an
      automated manner with high accuracy, and we also provide the corresponding shape
      factor analysis, which can be used synergistically with the CNN analysis for more
      robust predictions. Moreover, the trained deep CNN exhibits good performance even
      for a deoxygenated dataset and distinguishes the subtle differences in texture
      alteration inside the oxygenated and deoxygenated RBCs.

PMID- 29049292
TI  - Rejection sensitivity as a vulnerability marker for depressive symptom
      deterioration in men.
AB  - Consistent across time and cultures, men and male adolescents older than 14 years
      of age appear underrepresented in mood disorders, and are far less likely than
      women to seek psychological help. The much higher rate of suicide amongst males
      suggests that depression in men might be underreported. One of the core human
      motives is to seek acceptance by others and avoid rejection. Rejection
      Sensitivity (RS) has been conceptualized as the cognitive-affective processing
      disposition to anxiously expect, readily perceive, and intensely respond to cues
      of rejection in the behavior of others. RS has been previously linked with the
      onset and course of depression, but-as yet-has not been investigated
      longitudinally in a clinical population. We investigated the predictive role of
      RS to symptom deterioration 6 months after end-of- treatment in 72 male
      inpatients with depressive spectrum disorder. The BDI was administered at intake,
      end-of-treatment and 6 month follow-up. RS scores were obtained at intake.
      Rejection Sensitivity had additional predictive power on BDI scores at 6 months
      follow-up controlling for BDI scores at end-of-treatment (DeltaR2 = .095). The
      results are discussed in terms of the importance of targeting RS during
      treatment, and highlight the fact that therapeutic follow-up care is paramount.
      Future research should investigate possible mediators of the RS-relapse-to
      depression association, such as self-blame, rumination, neuroticism, pessimism,
      emotion dysregulation, and low self-esteem.

PMID- 29049293
TI  - A structural equation model of the relationship between muscle strength, balance
      performance, walking endurance and community integration in stroke survivors.
AB  - PURPOSE: To use structural equation modelling (SEM) to determine (1) the direct
      and indirect associations of strength of paretic lower limb muscles with the
      level of community integration, and (2) the direct association of walking
      endurance and balance performance with the level of community integration in
      community-dwelling stroke survivors. MATERIALS AND METHODS: In this cross
      sectional study of 105 stroke survivors, the Subjective Index of Physical and
      Social Outcome (SIPSO) was used to measure the level of community integration.
      Lower-limb strength measures included isometric paretic ankle strength and
      isokinetic paretic knee peak torque. The Berg Balance Scale (BBS) and the 6
      minute walk test (6MWT) were used to evaluate balance performance and walking
      endurance, respectively. RESULTS: SEM revealed that the distance walked on the
      6MWT had the strongest direct association with the SIPSO score (beta = 0.41, p
      <0.001). An increase of one standard deviation in the 6MWT distance resulted in
      an increase of 0.41 standard deviations in the SIPSO score. Moreover,
      dorsiflexion strength (beta = 0.18, p = 0.044) and the BBS score (beta = 0.21, p
      = 0.021) had direct associations with the SIPSO score. CONCLUSIONS: The results
      of the proposed model suggest that rehabilitation training of community-dwelling
      stroke survivors could focus on walking endurance, balance performance and
      dorsiflexor muscle strengthening if the aim is to augment the level of community
      integration.

PMID- 29049294
TI  - Impact of dynamic changes of elevated bilirubin on survival in patients on veno
      arterial extracorporeal life support for acute circulatory failure.
AB  - AIMS: Veno-arterial extracorporeal life support (ECLS) is an established method
      to stabilize acute circulatory failure. Parameters and data on when to ideally
      wean circulatory support are limited. Bilirubin is a marker of end-organ damage.
      Therefore, the purpose of this large study was to evaluate the impact of dynamic
      changes of elevated bilirubin levels on survival in patients on ECLS. METHODS AND
      RESULTS: We reviewed 502 consecutive cases of ECLS from 2007 to 2015. Bilirubin
      levels were recorded before implantation and until six days after explantation.
      Dynamic bilirubin changes, and hemodynamic and laboratory outcome parameters were
      compared in survivors and nonsurvivors. Reason for ECLS implantation was cardiac
      arrest with ongoing resuscitation in 230 (45.8%), low cardiac output in 174
      (34.7%) and inability to wean off cardiopulmonary bypass in 98 (19.5%) patients.
      307 (61.2%) patients were weaned off ECLS, however, 206 (41.0%) survived. Mean
      duration of ECLS was 3 (2-6) days, and survivors received significantly longer
      ECLS (5 vs 3 days, p < 0.001). Survivors had significantly lower baseline
      bilirubin levels (p = 0.003). Bilirubin started to rise from day 2 in all
      patients. In survivors, bilirubin levels had trended down on the day of ECLS
      explantation and stayed at an acceptable level. However, in weaned patients who
      did not survive and patients who died on ECLS bilirubin levels continued to rise
      during the recorded period. CONCLUSION: ECLS support improves survival in
      patients with acute circulatory failure. Down trending bilirubin levels on veno
      arterial ECLS indicate improved chances of successful weaning and survival in
      hemodynamically stable patients.

PMID- 29049295
TI  - Inferring gene and protein interactions using PubMed citations and consensus
      Bayesian networks.
AB  - The PubMed database offers an extensive set of publication data that can be
      useful, yet inherently complex to use without automated computational techniques.
      Data repositories such as the Genomic Data Commons (GDC) and the Gene Expression
      Omnibus (GEO) offer experimental data storage and retrieval as well as curated
      gene expression profiles. Genetic interaction databases, including Reactome and
      Ingenuity Pathway Analysis, offer pathway and experiment data analysis using data
      curated from these publications and data repositories. We have created a method
      to generate and analyze consensus networks, inferring potential gene
      interactions, using large numbers of Bayesian networks generated by data mining
      publications in the PubMed database. Through the concept of network resolution,
      these consensus networks can be tailored to represent possible genetic
      interactions. We designed a set of experiments to confirm that our method is
      stable across variation in both sample and topological input sizes. Using gene
      product interactions from the KEGG pathway database and data mining PubMed
      publication abstracts, we verify that regardless of the network resolution or the
      inferred consensus network, our method is capable of inferring meaningful gene
      interactions through consensus Bayesian network generation with multiple,
      randomized topological orderings. Our method can not only confirm the existence
      of currently accepted interactions, but has the potential to hypothesize new ones
      as well. We show our method confirms the existence of known gene interactions
      such as JAK-STAT-PI3K-AKT-mTOR, infers novel gene interactions such as RAS- Bcl-2
      and RAS-AKT, and found significant pathway-pathway interactions between the JAK
      STAT signaling and Cardiac Muscle Contraction KEGG pathways.

PMID- 29049296
TI  - Genome-wide expression analysis of salt-stressed diploid and autotetraploid
      Paulownia tomentosa.
AB  - Paulownia tomentosa is a fast-growing tree species with multiple uses. It is
      grown worldwide, but is native to China, where it is widely cultivated in saline
      regions. We previously confirmed that autotetraploid P. tomentosa plants are more
      stress-tolerant than the diploid plants. However, the molecular mechanism
      underlying P. tomentosa salinity tolerance has not been fully characterized.
      Using the complete Paulownia fortunei genome as a reference, we applied next
      generation RNA-sequencing technology to analyze the effects of salt stress on
      diploid and autotetraploid P. tomentosa plants. We generated 175 million clean
      reads and identified 15,873 differentially expressed genes (DEGs) from four P.
      tomentosa libraries (two diploid and two autotetraploid). Functional annotations
      of the differentially expressed genes using the Gene Ontology and Kyoto
      Encyclopedia of Genes and Genomes databases revealed that plant hormone signal
      transduction and photosynthetic activities are vital for plant responses to high
      salt conditions. We also identified several transcription factors, including
      members of the AP2/EREBP, bHLH, MYB, and NAC families. Quantitative real-time PCR
      analysis validated the expression patterns of eight differentially expressed
      genes. Our findings and the generated transcriptome data may help to accelerate
      the genetic improvement of cultivated P. tomentosa and other plant species for
      enhanced growth in saline soils.

PMID- 29049297
TI  - Functional connectivity structure of cortical calcium dynamics in anesthetized
      and awake mice.
AB  - The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI
      and optical intrinsic signal imaging), which are an indirect and relatively slow
      report of neural activity, and underlying synaptic electrical and metabolic
      activity through neurovascular coupling is a topic of ongoing research and
      debate. As application of resting state functional connectivity measures is
      extended further into topics such as brain development, aging and disease, the
      importance of understanding the fundamental physiological basis for functional
      connectivity will grow. Here we extend functional connectivity analysis from
      hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a
      fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in
      glutamatergic neurons were imaged transcranially in both anesthetized (using
      ketamine/xylazine) and awake states. Sequential LED illumination (lambda = 454,
      523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission
      (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity
      network maps were constructed for infraslow (0.009-0.08Hz), intermediate (0.08
      0.4Hz), and high (0.4-4.0Hz) frequency bands. At infraslow and intermediate
      frequencies, commonly used in BOLD fMRI and fcOIS studies of functional
      connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2
      functional connectivity structures were in high agreement, both qualitatively and
      also quantitatively through a measure of spatial similarity. The spontaneous
      dynamics of both contrasts had the highest correlation when the GCaMP6 signal was
      delayed with a ~0.6-1.5s temporal offset. Within the higher-frequency delta band,
      sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we
      evaluate the speed with which the connectivity analysis stabilized and found that
      the functional connectivity maps captured putative network structure within time
      window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity
      maps at 0.4-4.0Hz in the anesthetized states show a striking correlated and anti
      correlated structure along the anterior to posterior axis. This structure is
      potentially explained in part by observed propagation of delta-band activity from
      frontal somatomotor regions to visuoparietal areas. During awake imaging, this
      spatio-temporal quality is altered, and a more complex and detailed functional
      connectivity structure is observed. The combined calcium/hemoglobin imaging
      technique described here will enable the dissociation of changes in ionic and
      hemodynamic functional structure and neurovascular coupling and provide a
      framework for subsequent studies of neurological disease such as stroke.

PMID- 29049298
TI  - Using worldwide edaphic data to model plant species niches: An assessment at a
      continental extent.
AB  - Ecological niche modeling (ENM) is a broadly used tool in different fields of
      plant ecology. Despite the importance of edaphic conditions in determining the
      niche of terrestrial plant species, edaphic data have rarely been included in
      ENMs of plant species perhaps because such data are not available for many
      regions. Recently, edaphic data has been made available at a global scale
      allowing its potential inclusion and evaluation on ENM performance for plant
      species. Here, we take advantage of such data and address the following main
      questions: What is the influence of distinct predictor variables (e.g. climatic
      vs edaphic) on different ENM algorithms? and what is the relationship between the
      performance of different predictors and geographic characteristics of species? We
      used 125 plant species distributed over the Neotropical region to explore the
      effect on ENMs of using edaphic data available from the SoilGrids database and
      its combination with climatic data from the CHELSA database. In addition, we
      related these different predictor variables to geographic characteristics of the
      target species and different ENM algorithms. The use of different predictors
      (climatic, edaphic, and both) significantly affected model performance and
      spatial complexity of the predictions. We showed that the use of global edaphic
      plus climatic variables generates ENMs with similar or better accuracy compared
      to those constructed only with climate variables. Moreover, the performance of
      models considering these different predictors, separately or jointly, was related
      to geographic properties of species records, such as number and distribution
      range. The large geographic extent, the variability of environments and the
      different species' geographical characteristics considered here allowed us to
      demonstrate that global edaphic data adds useful information for plant ENMs. This
      is particularly valuable for studies of species that are distributed in regions
      where more detailed information on soil properties is poor or does not even
      exist.

PMID- 29049299
TI  - Evans blue dye-enhanced imaging of the brain microvessels using spectral focusing
      coherent anti-Stokes Raman scattering microscopy.
AB  - We performed dye-enhanced imaging of mouse brain microvessels using spectral
      focusing coherent anti-Stokes Raman scattering (SF-CARS) microscopy. The resonant
      signals from C-H stretching in forward CARS usually show high background
      intensity in tissues, which makes CARS imaging of microvessels difficult. In this
      study, epi-detection of back-scattered SF-CARS signals showed a negligible
      background, but the overall intensity of resonant CARS signals was too low to
      observe the network of brain microvessels. Therefore, Evans blue (EB) dye was
      used as contrasting agent to enhance the back-scattered SF-CARS signals.
      Breakdown of brain microvessels by inducing hemorrhage in a mouse was clearly
      visualized using backward SF-CARS signals, following intravenous injection of EB.
      The improved visualization of brain microvessels with EB enhanced the sensitivity
      of SF-CARS, detecting not only the blood vessels themselves but their integrity
      as well in the brain vasculature.

PMID- 29049300
TI  - Increased cell survival and cytogenetic integrity by spatial dose redistribution
      at a compact synchrotron X-ray source.
AB  - X-ray microbeam radiotherapy can potentially widen the therapeutic window due to
      a geometrical redistribution of the dose. However, high requirements on photon
      flux, beam collimation, and system stability restrict its application mainly to
      large-scale, cost-intensive synchrotron facilities. With a unique laser-based
      Compact Light Source using inverse Compton scattering, we investigated the
      translation of this promising radiotherapy technique to a machine of future
      clinical relevance. We performed in vitro colony-forming assays and chromosome
      aberration tests in normal tissue cells after microbeam irradiation compared to
      homogeneous irradiation at the same mean dose using 25 keV X-rays. The
      microplanar pattern was achieved with a tungsten slit array of 50 MUm slit size
      and a spacing of 350 MUm. Applying microbeams significantly increased cell
      survival for a mean dose above 2 Gy, which indicates fewer normal tissue
      complications. The observation of significantly less chromosome aberrations
      suggests a lower risk of second cancer development. Our findings provide valuable
      insight into the mechanisms of microbeam radiotherapy and prove its applicability
      at a compact synchrotron, which contributes to its future clinical translation.

PMID- 29049302
TI  - Connectivity maps based analysis of EEG for the advanced diagnosis of
      schizophrenia attributes.
AB  - This article presents a novel connectivity analysis method that is suitable for
      multi-node networks such as EEG, MEG or EcOG electrode recordings. Its diagnostic
      power and ability to interpret brain states in schizophrenia is demonstrated on a
      set of 50 subjects that constituted of 25 healthy and 25 diagnosed with
      schizophrenia and treated with medication. The method can also be used for the
      automatic detection of schizophrenia; it exhibits higher sensitivity than state
      of-the-art methods with no false positives. The detection is based on an analysis
      from a minute long pattern-recognition computer task. Moreover, this connectivity
      analysis leads naturally to an optimal choice of electrodes and hence to highly
      statistically significant results that are based on data from only 3-5
      electrodes. The method is general and can be used for the diagnosis of other
      psychiatric conditions, provided an appropriate computer task is devised.

PMID- 29049301
TI  - Plant DNA barcodes and assessment of phylogenetic community structure of a
      tropical mixed dipterocarp forest in Brunei Darussalam (Borneo).
AB  - DNA barcoding is a fast and reliable tool to assess and monitor biodiversity and,
      via community phylogenetics, to investigate ecological and evolutionary processes
      that may be responsible for the community structure of forests. In this study,
      DNA barcodes for the two widely used plastid coding regions rbcL and matK are
      used to contribute to identification of morphologically undetermined individuals,
      as well as to investigate phylogenetic structure of tree communities in 70
      subplots (10 * 10m) of a 25-ha forest-dynamics plot in Brunei (Borneo, Southeast
      Asia). The combined matrix (rbcL + matK) comprised 555 haplotypes (from >=154
      genera, 68 families and 25 orders sensu APG, Angiosperm Phylogeny Group, 2016),
      making a substantial contribution to tree barcode sequences from Southeast Asia.
      Barcode sequences were used to reconstruct phylogenetic relationships using
      maximum likelihood, both with and without constraining the topology of taxonomic
      orders to match that proposed by the Angiosperm Phylogeny Group. A third
      phylogenetic tree was reconstructed using the program Phylomatic to investigate
      the influence of phylogenetic resolution on results. Detection of non-random
      patterns of community assembly was determined by net relatedness index (NRI) and
      nearest taxon index (NTI). In most cases, community assembly was either random or
      phylogenetically clustered, which likely indicates the importance to community
      structure of habitat filtering based on phylogenetically correlated traits in
      determining community structure. Different phylogenetic trees gave similar
      overall results, but the Phylomatic tree produced greater variation across plots
      for NRI and NTI values, presumably due to noise introduced by using an unresolved
      phylogenetic tree. Our results suggest that using a DNA barcode tree has benefits
      over the traditionally used Phylomatic approach by increasing precision and
      accuracy and allowing the incorporation of taxonomically unidentified individuals
      into analyses.

PMID- 29049303
TI  - A Mediterranean diet with additional extra virgin olive oil and pistachios
      reduces the incidence of gestational diabetes mellitus (GDM): A randomized
      controlled trial: The St. Carlos GDM prevention study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) prevalence is increasing and
      becoming a major public health concern. Whether a Mediterranean diet can help
      prevent GDM in unselected pregnant women has yet to be studied. METHODS: We
      conducted a prospective, randomized controlled trial to evaluate the incidence of
      GDM with two different dietary models. All consecutive normoglycemic (<92 mg/dL)
      pregnant women at 8-12 gestational weeks (GW) were assigned to Intervention Group
      (IG, n = 500): MedDiet supplemented with extra virgin olive oil (EVOO) and
      pistachios; or Control Group (CG, n = 500): standard diet with limited fat
      intake. Primary outcome was to assess the effect of the intervention on GDM
      incidence at 24-28 GW. Gestational weight gain (GWG), pregnancy-induced
      hypertension, caesarean section (CS), preterm delivery, perineal trauma, small
      and large for gestational age (SGA and LGA) and admissions to neonatal intensive
      care unit were also assessed. Analysis was by intention-to-treat. RESULTS: A
      total of 874 women completed the study (440/434, CG/IG). According to nutritional
      questionnaires and biomarker analysis, women in the IG had a good adherence to
      the intervention. 177/874 women were diagnosed with GDM, 103/440 (23.4%) in CG
      and 74/434(17.1%) in IG, p = 0.012. The crude relative risk (RR) for GDM was 0.73
      (95% CI: 0.56-0.95; p = 0.020) IG vs CG and persisted after adjusted
      multivariable analysis, 0.75(95% CI: 0.57-0.98; p = 0.039). IG had also
      significantly reduced rates of insulin-treated GDM, prematurity, GWG at 24-28 and
      36-38 GW, emergency CS, perineal trauma, and SGA and LGA newborns (all p<0.05).
      CONCLUSIONS: An early nutritional intervention with a supplemented MedDiet
      reduces the incidence of GDM and improves several maternal and neonatal outcomes.

PMID- 29049304
TI  - Investigation of surface topography and stiffness on adhesion and neurites
      extension of PC12 cells on crosslinked silica aerogel substrates.
AB  - Fundamental understanding and characterization of neural response to substrate
      topography is essential in the development of next generation biomaterials for
      nerve repair. Aerogels are a new class of materials with great potential as a
      biomaterial. In this work, we examine the extension of neurites by PC12 cells
      plated on matrigel-coated and collagen-coated mesoporous aerogel surfaces. We
      have successfully established the methodology for adhesion and growth of PC12
      cells on polyurea crosslinked silica aerogels. Additionally, we have quantified
      neurite behaviors and compared their response on aerogel substrates with their
      behavior on tissue culture (TC) plastic, and polydimethylsiloxane (PDMS). We
      found that, on average, PC12 cells extend longer neurites on crosslinked silica
      aerogels than on tissue culture plastic, and, that the average number of neurites
      per cluster is lower on aerogels than on tissue culture plastic. Aerogels are an
      attractive candidate for future development of smart neural implants and the work
      presented here creates a platform for future work with this class of materials as
      a substrate for bioelectronic interfacing.

PMID- 29049305
TI  - Pig movements in France: Designing network models fitting the transmission route
      of pathogens.
AB  - Pathogen spread between farms results from interaction between the
      epidemiological characteristics of infectious agents, such as transmission route,
      and the contact structure between holdings. The objective of our study was to
      design network models of pig movements matching with epidemiological features of
      pathogens. Our first model represents the transmission of infectious diseases
      between farms only through the introduction of animals to holdings (Animal
      Introduction Model AIM), whereas the second one also accounts for pathogen spread
      through intermediate transit of trucks through farms even without any animal
      unloading (i.e. indirect transmission-Transit Model TM). To take the pyramidal
      organisation of pig production into consideration, these networks were studied at
      three different scales: the whole network and two subnetworks containing only
      breeding or production farms. The two models were applied to pig movement data
      recorded in France from June 2012 to December 2014. For each type of model, we
      calculated network descriptive statistics, looked for weakly/strongly connected
      components (WCCs/SCCs) and communities, and analysed temporal patterns. Whatever
      the model, the network exhibited scale-free and small-world topologies.
      Differences in centrality values between the two models showed that nucleus,
      multiplication and post-weaning farms played a key role in the spread of diseases
      transmitted exclusively by the introduction of infected animals, whereas
      farrowing and farrow-to-finish herds appeared more vulnerable to the introduction
      of infectious diseases through indirect contacts. The second network was less
      fragmented than the first one, a giant SCC being detected. The topology of
      network communities also varied with modelling assumptions: in the first
      approach, a huge geographically dispersed community was found, whereas the second
      model highlighted several small geographically clustered communities. These
      results underline the relevance of developing network models corresponding to
      pathogen features (e.g. their transmission route), and the need to target
      specific types of holdings/areas for surveillance depending on the
      epidemiological context.

PMID- 29049307
TI  - DOMe: A deduplication optimization method for the NewSQL database backups.
AB  - Reducing duplicated data of database backups is an important application scenario
      for data deduplication technology. NewSQL is an emerging database system and is
      now being used more and more widely. NewSQL systems need to improve data
      reliability by periodically backing up in-memory data, resulting in a lot of
      duplicated data. The traditional deduplication method is not optimized for the
      NewSQL server system and cannot take full advantage of hardware resources to
      optimize deduplication performance. A recent research pointed out that the future
      NewSQL server will have thousands of CPU cores, large DRAM and huge NVRAM.
      Therefore, how to utilize these hardware resources to optimize the performance of
      data deduplication is an important issue. To solve this problem, we propose a
      deduplication optimization method (DOMe) for NewSQL system backup. To take
      advantage of the large number of CPU cores in the NewSQL server to optimize
      deduplication performance, DOMe parallelizes the deduplication method based on
      the fork-join framework. The fingerprint index, which is the key data structure
      in the deduplication process, is implemented as pure in-memory hash table, which
      makes full use of the large DRAM in NewSQL system, eliminating the performance
      bottleneck problem of fingerprint index existing in traditional deduplication
      method. The H-store is used as a typical NewSQL database system to implement DOMe
      method. DOMe is experimentally analyzed by two representative backup data. The
      experimental results show that: 1) DOMe can reduce the duplicated NewSQL backup
      data. 2) DOMe significantly improves deduplication performance by parallelizing
      CDC algorithms. In the case of the theoretical speedup ratio of the server is
      20.8, the speedup ratio of DOMe can achieve up to 18; 3) DOMe improved the
      deduplication throughput by 1.5 times through the pure in-memory index
      optimization method.

PMID- 29049306
TI  - Protein structural disorder of the envelope V3 loop contributes to the switch in
      human immunodeficiency virus type 1 cell tropism.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope gp120 is partly an
      intrinsically disordered (unstructured/disordered) protein as it contains regions
      that do not fold into well-defined protein structures. These disordered regions
      play important roles in HIV's life cycle, particularly, V3 loop-dependent cell
      entry, which determines how the virus uses two coreceptors on immune cells, the
      chemokine receptors CCR5 (R5), CXCR4 (X4) or both (R5X4 virus). Most infecting
      HIV-1 variants utilise CCR5, while a switch to CXCR4-use occurs in the majority
      of infections. Why does this 'rewiring' event occur in HIV-1 infected patients?
      As changes in the charge of the V3 loop are associated with this receptor switch
      and it has been suggested that charged residues promote structure disorder, we
      hypothesise that the intrinsic disorder of the V3 loop is permissive to sequence
      variation thus contributing to the switch in cell tropism. To test this we use
      three independent data sets of gp120 to analyse V3 loop disorder. We find that
      the V3 loop of X4 virus has significantly higher intrinsic disorder tendency than
      R5 and R5X4 virus, while R5X4 virus has the lowest. These results indicate that
      structural disorder plays an important role in HIV-1 cell tropism and CXCR4
      binding. We discuss the potential evolutionary mechanisms leading to the fixation
      of disorder promoting mutations and the adaptive potential of protein structural
      disorder in viral host adaptation.

PMID- 29049308
TI  - The relationship between intradialytic hypotension and vascular calcification in
      hemodialysis patients.
AB  - BACKGROUND: Vascular calcification is associated with structural and functional
      abnormality of the heart and blood vessels. We investigated the relationship
      between intradialytic hypotension (IDH) and vascular calcification in
      hemodialysis (HD) patients, and their impacts on cardiovascular events (CVEs).
      METHOD: We enrolled 191 maintenance HD patients who underwent plain abdomen
      radiography for abdominal aortic calcification score (AACS). A nadir systolic
      blood pressure (BP) < 90 mm Hg or the requirement of bolus fluid administration
      was required to quantify the hypotension diagnosis. IDH was defined as > 2
      hypotension episodes during 10 HD treatments. RESULTS: Among the 191 patients,
      IDH occurred in 32. AACS was higher in the IDH group compared with the no-IDH
      group (8.4 +/- 6.0 vs. 4.9 +/- 5.2, respectively; P = 0.001). High AACS was an
      independent risk factor after adjustment for age, diabetes mellitus,
      ultrafiltration, diastolic BP, and calcium level (odds ratio (OR) = 1.09, 95% CI
      = 1.01-1.18; P = 0.03). Patients with both IDH and AACS ? 4 had the highest
      cumulative CVE rate (27.9%, P = 0.008) compared with 11.2%, 12.5%, and 6% for
      those with AACS ? 4 only, with IDH only, and neither, respectively. In
      multivariate analysis, the presence of both IDH and AACS ? 4 was a significant
      predictor of CVE (hazard ratio (HR) = 2.84, 95% CI = 1.04-7.74, P = 0.04).
      CONCLUSION: IDH is associated with abdominal aortic calcification and is an
      independent risk factor for IDH. Both IDH and high AACS were significant
      predictors of CVE.

PMID- 29049309
TI  - Validation of surrogate markers for metabolic syndrome and cardiometabolic risk
      factor clustering in children and adolescents: A nationwide population-based
      study.
AB  - Prevalence of metabolic syndrome (MetS) in children is increasing and identifying
      the risk factors for MetS during childhood is an important first step to prevent
      chronic diseases later in life. The aim of the present study was to evaluate the
      prevalence of MetS and cardiometabolic risk factor (CMRF) clustering among Korean
      children and adolescents and to validate the associated anthropometric and
      laboratory surrogate markers. We used data from the 2011-2014 Korean National
      Health and Nutrition Examination Survey. In total, data for 2,935 subjects (1539
      boys, 52.6%) aged 10-19 years were assessed. MetS was defined by central obesity
      plus any two or more of CMRFs such as abdominal obesity, hypertension,
      hyperglycemia, hypertriglyceridemia, and decreased high density lipoprotein
      cholesterol (HDL-C) using the International Diabetes Federation criteria for
      children and adolescents. The presence of two or more CMRFs was classified as
      CMRF clustering. The prevalence of MetS and CMRF clustering in this group was
      found to be 1.8% and 8.9%, respectively. The receiver operating characteristic
      analysis of MetS and CMRF clustering, and the area under the curve (95%
      confidence interval) of surrogate markers revealed that the waist circumference
      to height ratio [0.960 (95% CI 0.959-0.960), cut-off 0.491] showed the highest
      predictability for MetS whereas triglyceride to HDL-C ratio [0.891 (95% CI 0.891
      0.892), cut-off 2.63] showed the highest predictability for CMRF clustering. Long
      term follow-up is needed for further validation.

PMID- 29049310
TI  - Molecular epidemiology of influenza B virus among hospitalized pediatric patients
      in Northern Italy during the 2015-16 season.
AB  - BACKGROUND: The influenza B viruses belong to two lineages distinguished by their
      genetic and antigenic characteristics, which are referred to as the Yamagata and
      Victoria lineages, designated after their original isolates, B/Yamagata/16/88 and
      B/Victoria/2/87. The primary aim of this study was to evaluate the molecular
      characteristics of influenza B viruses circulating in a region of Northern Italy,
      Lombardia, during the influenza season of 2015-2016. METHODS: Influenza B virus
      was detected using a respiratory virus panel of assays and an influenza B
      specific real-time polymerase chain reaction. The complete influenza B
      hemagglutinin (HA) gene was amplified and sequenced directly from clinical
      specimens. Phylogenetic analysis was performed using nucleotide sequences.
      RESULTS: A total of 71 hospitalized pediatric patients were influenza B positive.
      Phylogenetic analysis showed that the great majority of influenza B strains
      (66/71, 93.0%) belonged to the Victoria-lineage and were antigenically like
      vaccine strain (B/Brisbane/60/2008) included only in the quadrivalent vaccine. In
      the detected influenza B strains, a series of amino acid changes were observed in
      the antigenic regions: I117V, V124A, N129D, V146I, N197D, T199A, and A202T.
      However, only 2 amino acid changes were observed in the HA regions involved in
      receptor binding or in antibody recognition. CONCLUSIONS: All the influenza B
      strains identified in this study belonged to the influenza B Victoria lineage not
      included in the trivalent vaccine commonly used by the general population during
      the 2015-2016 influenza season in Italy. This indicates that protection against
      influenza B infection in the vaccinated population was in general very poor
      during the 2015-2016 influenza season.

PMID- 29049311
TI  - A kinase inhibitor library screen identifies novel enzymes involved in ototoxic
      damage to the murine organ of Corti.
AB  - Ototoxicity is a significant side effect of a number of drugs, including the
      aminoglycoside antibiotics and platinum-based chemotherapeutic agents that are
      used to treat life-threatening illnesses. Although much progress has been made,
      the mechanisms that lead to ototoxic loss of inner ear sensory hair cells (HCs)
      remains incompletely understood. Given the critical role of protein
      phosphorylation in intracellular processes, including both damage and survival
      signaling, we screened a library of kinase inhibitors targeting members of all
      the major families in the kinome. Micro-explants from the organ of Corti of mice
      in which only the sensory cells express GFP were exposed to 200 MUM of the
      ototoxic aminoglycoside gentamicin with or without three dosages of each kinase
      inhibitor. The loss of sensory cells was compared to that seen with gentamicin
      alone, or without treatment. Of the 160 inhibitors, 15 exhibited a statistically
      significant protective effect, while 3 significantly enhanced HC loss. The
      results confirm some previous studies of kinase involvement in HC damage and
      survival, and also highlight several novel potential kinase pathway contributions
      to ototoxicity.

PMID- 29049312
TI  - Impact of annotation error in alpha-globin genes on molecular diagnosis.
AB  - BACKGROUND: Recent studies on the variants in duplicated human alpha globin genes
      (HBA2 and HBA1) actively target the alpha-globin gene as molecular modulators for
      the treatment of beta-thalassemia major. Identification of the exact position of
      variant in HBA1, HBA2 or its patchworks is mandatory to support the therapeutic
      aims in beta-thalassemia major, by identifying specific modulators for the
      reactivation of fetal hemoglobin production. Hence, accurate identification of
      the variants in alpha-globin genes is crucial for the proper diagnosis, treatment
      and genetic counseling. METHOD: The objective was to reveal the annotation errors
      produced in alpha-globin gene sequence analysis while using different analytic
      tools. An HBA2 gene sequence with the HBA2:c.95+2_95+6delTGAGG variant and a
      recently reported HBA12 gene convert have been taken as examples to prove
      annotation error in alpha-globin gene from different analytic tools. RESULTS AND
      DISCUSSION: Although various bioinformatics tools used to predict variants are
      usually of high reliability, the current study using the an alpha globin 2
      sequence with the HBA2:c.95+2_95+6delTGAGG variant and a recently reported HBA12
      gene convert, has showcased ambiguous outputs among the three bioinformatics
      tools used and against the manual analytical method adopted. CONCLUSIONS: This
      report emphasizes the necessity for caution in the usage of DNA sequence analysis
      tools during molecular diagnosis and the importance of the selection of more
      appropriate tools for analysis. Furthermore, ethnic specific sequences should be
      considered as reference sequence for the analysis to bypass sequence
      dissimilarities among diverse populations.

PMID- 29049313
TI  - Study on association of working hours and occupational physical activity with the
      occurrence of coronary heart disease in a Chinese population.
AB  - OBJECTIVE: To explore the association of working hours and occupational physical
      activity (OPA) with the occurrence of coronary heart disease (CHD) in a Chinese
      population. METHODS: A total of 595 participants (354 and 241 patients with and
      without CHD, respectively) aged between 24 and 65 were enrolled in our study,
      which was conducted at the First Affiliated Hospital of Nanjing Medical
      University between December 2015 and October 2016. Participant characteristics
      were collected from face-to-face questionnaires, and logistic regression analysis
      was conducted to examine the association of working hours and OPA with the
      occurrence of CHD. RESULTS: Compared with non-employed people, long working hours
      (especially >=55 hours/week) contributed to the occurrence of CHD (adjusted odds
      ratio[OR] = 2.213, 95% confidence interval [CI]: 1.125, 4.355, P = 0.021) after
      multivariate adjustment in the Chinese population. With the extension of
      worktime, the CHD risk increased (P for the dose-response trend = 0.022).
      Meanwhile, even after adjusting for engagement in physical activity during
      leisure time, sedentary behavior at work had an adverse effect on CHD risk
      (adjusted OR = 2.794, 95%CI: 1.526, 5.115, P = 0.001), and a linear relationship
      was also found between OPA and CHD (P for the trend = 0.005). CONCLUSIONS: Long
      working hours and sedentary behavior at work are associated with a high risk of
      CHD. In addition, prolonged working hours in sedentary occupations increases the
      risk of CHD, independent of engagement in leisure time physical activity.

PMID- 29049314
TI  - Evaluation of characteristic of human turbinate derived mesenchymal stem cells
      cultured in the serum free media.
AB  - We evaluated the effect of serum-free and xeno-cultivation (SFXFM) on the
      characterization, proliferation, and differentiation properties of human nasal
      stem cells (airway tissue; hTMSCs). hTMSCs were isolated from 10 patients, after
      which patient samples were separated into two groups, an SFXFM group and a
      control group. The control group was treated with bovine serum-containing medium.
      FACS analysis revealed that SFXFM-cultured hTMSCs maintained a characteristic
      mesenchymal stem cell phenotype. hTMSC proliferation was not influenced by SFXFM.
      In addition, upregulation of IL-8 and GM-CSF and downregulation of RANTES
      expression were shown in response to SFXFM. Moreover, two-lineage differentiation
      properties (osteocyte and adipocyte) of hTMSCs were enhanced under SFXFM.
      Finally, the genetic stability of SFXFM-cultured hTMSCs was demonstrated by
      normal karyotype results. SFXFM enables good expansion, multipotentiality, and
      normal genotype maintenance of MSCs. Moreover, this approach serves as a
      substitute to conventional media for the cultivation of capable MSCs for upcoming
      medical applications.

PMID- 29049315
TI  - Analysis of the interests of Google users on toothache information.
AB  - BACKGROUND: The knowledge on health interests of a given population of Internet
      users might contribute to the increase of evidence on community's dental needs,
      and consequently, to the improvement of public health planning. The frequency of
      searches for specific issues on Google can be analyzed by the application of
      Google Trends. AIM: In this study, we aimed to characterize the interests on
      toothache information of Google users from the United States, United Kingdom,
      Australia and Brazil. METHODS: The monthly variation of relative search volume
      (RSV) and the lists of main toothache-related queries were determined from
      January 2004 through April 2016 using Google Trends. Autoregressive Integrated
      Moving Average (ARIMA) forecasting models were developed to determine predictive
      RSV values for toothache for additional 12 months. Autocorrelation plots and
      general additive model (GAM) were applied to determine trends and seasonality in
      RSV curves. Through linear regression models, we assessed the association between
      the variation of annual means of RSV values and national statistics for toothache
      in the U.S. and U.K. Subsequently, the distribution of main queries according to
      the identification of endodontic pain, type of searching information, and the
      interest in self-management of toothache was evaluated for the four countries.
      RESULTS: The autocorrelation plots showed patterns of non-stationary time series.
      The monthly variation influenced the data of the U.S. and U.K., with the higher
      RSV values found respectively in January/July and December. Also, the interest on
      toothache in the U.K. increases in the second semester and in the fourth quarter,
      especially in December. Additionally, an annual variation affected significantly
      all time series, with the increment of RSV means over the years, varying from
      265% in the U.S. to 745% in Brazil. In parallel, the increments in RSV values
      were also observed in all predictive curves. The annual variation of observed and
      fitted RSV values was directly associated with the increase of toothache visits
      in the U.S. and urgent dental treatments in the U.K. Moreover, the queries typed
      on Google were markedly linked to searches on endodontic pain information,
      especially in Brazil, where the residents usually searched for relief and/or self
      management of pain. CONCLUSIONS: Therefore, these findings indicate an increasing
      interest of Google users on toothache-related topics, regardless of country and
      season. The Internet activity can be used by policy makers as a complementary
      source of data for the development and implementation of strategies to control
      and prevent toothache complications.

PMID- 29049316
TI  - Genomic comparison of early-passage conditionally reprogrammed breast cancer
      cells to their corresponding primary tumors.
AB  - Conditionally reprogrammed cells (CRCs) are epithelial cells that are directly
      isolated from patients' specimens and propagated in vitro with feeder cells and a
      Rho kinase inhibitor. A number of these cells have been generated from biopsies
      of breast cancer patients, including ductal carcinoma in situ and invasive
      carcinomas. The characterization of their genomic signatures is essential to
      determine their ability to reflect the natural biology of their tumors of origin.
      In this study, we performed the genomic characterization of six newly established
      invasive breast cancer CRC cultures in comparison to the original patients'
      primary breast tumors (PBT) from which they derived. The CRCs and corresponding
      PBTs were simultaneously profiled by genome-wide array-CGH, targeted next
      generation sequencing and global miRNA expression to determine their molecular
      similarities in the patterns of copy number alterations (CNAs), gene mutations
      and miRNA expression levels, respectively. The CRCs' epithelial cells content and
      ploidy levels were also evaluated by flow cytometry. A similar level of CNAs was
      observed in the pairs of CRCs/PBTs analyzed by array-CGH, with >95% of overlap
      for the most frequently affected cytobands. Consistently, targeted next
      generation sequencing analysis showed the retention of specific somatic variants
      in the CRCs as present in their original PBTs. Global miRNA profiling closely
      clustered the CRCs with their PBTs (Pearson Correlation, ANOVA paired test,
      P<0.05), indicating also similarity at the miRNA expression level; the retention
      of tumor-specific alterations in a subset of miRNAs in the CRCs was further
      confirmed by qRT-PCR. These data demonstrated that the human breast cancer CRCs
      of this study maintained at early passages the overall copy number, gene
      mutations and miRNA expression patterns of their original tumors. The further
      characterization of these cells by other molecular and cellular phenotypes at
      late cell passages, are required to further expand their use as a unique and
      representative ex-vivo tumor model for basic science and translational breast
      cancer studies.

PMID- 29049317
TI  - Identification of genome-wide targets of Olig2 in the adult mouse spinal cord
      using ChIP-Seq.
AB  - In jawed vertebrates, oligodendrocytes (OLs) are the myelin-producing glial cells
      responsible for ensheathment of axons within the central nervous system and are
      also crucial for remyelination following injury or disease. Olig2 is a crucial
      factor in the specification and differentiation of oligodendrocyte precursor
      cells (OPCs) that give rise to mature, myelin-producing OLs in the developing and
      postnatal CNS; however, its role in adulthood is less well understood. To
      investigate the role Olig2 plays in regulating gene expression in the adult OL
      lineage in a physiologically-relevant context, we performed chromatin
      immunoprecipitation followed by next generation sequencing analysis (ChIP-Seq)
      using whole spinal cord tissue harvested from adult mice. We found that many of
      the Olig2-bound sites were associated with genes with biological processes
      corresponding to OL differentiation (Nkx2.2, Nkx6.2, and Sip1), myelination and
      ensheathment (Mbp, Cldn11, and Mobp), as well as cell cycle and cytoskeletal
      regulation. This suggests Olig2 continues to play a critical role in processes
      related to OL differentiation and myelination well into adulthood.

PMID- 29049319
TI  - Clinical outcome and prognostic factors associated with invasive pulmonary
      aspergillosis: An 11-year follow-up report from Taiwan.
AB  - BACKGROUND: Invasive pulmonary aspergillosis (IPA) has high mortality rate but
      prognostic factors are not well established. The aim of our study was to evaluate
      the trend in in-hospital mortality over a period of 11 years and identify factors
      affecting the clinical outcomes of patients with IPA. METHOD: We conducted a
      nationwide inpatient population study using data from the Taiwan National Health
      Insurance Research Database. A total of 407 IPA patients from 2002 to 2012 were
      included in the study. Differences in demographics, comorbidities, and treatment
      were evaluated between in-hospital death group and survival group. Multivariate
      analysis was also performed to identify risk factors for mortality. RESULT: Male
      patients represented 63.14% of the patients (n = 257) and the mean age was 53.15
      +/- 20.93 years. Hematological cancer (n = 216, 53.07%) and diabetes mellitus (n
      = 75, 18.43%) were the most common underlying conditions. The overall case
      fatality rate was 30.22% with female slightly higher then male (32.67% versus
      28.79%). The in-hospital case fatality rate increased since 2002 and peaked in
      2006. It then declined over time with an in-hospital mortality of 25% in 2012.
      The in-hospital death group had a higher intubation rate (p<0.0001), a longer ICU
      stay (p = 0.0062), higher percentages of DM (p = 0.0412) and COPD (p = 0.0178),
      and a lower percentage of hematological cancer (p = 0.0079) as compared to
      survivor. The in-hospital death group was more likely to have steroid treatment
      (p<0.0001), develop acute renal failure (p<0.0001) and other infectious diseases
      (p = 0.0008) during hospitalization. Multivariate analysis identified female
      gender, older age (>= 65 years old), intubation, bone marrow transplantation,
      acute renal failure, other infectious diseases and steroid use as predictive
      factors for mortality. CONCLUSION: The present study shows the trend in mortality
      among patients with IPA over an 11-year period. Female gender, older age,
      intubation, bone marrow transplantation, acute renal failure, other infectious
      diseases and steroid use were identified as risk factors for mortality.

PMID- 29049318
TI  - Short-chain fatty acid receptors inhibit invasive phenotypes in breast cancer
      cells.
AB  - Short chain fatty acids (2 to 6 carbons in length) are ubiquitous lipids that are
      present in human plasma at micromolar concentrations. In addition to serving as
      metabolic precursors for lipid and carbohydrate synthesis, they also act as
      cognate ligands for two known G protein-coupled receptors (GPCRs), FFAR2 and
      FFAR3. While there is evidence that these receptors may inhibit the progression
      of colorectal cancer, their roles in breast cancer cells are largely unknown. We
      evaluated the effects of enforced overexpression of these receptors in two
      phenotypically distinct breast cancer cell lines: MCF7 and MDA-MD-231. Our
      results demonstrate that both receptors inhibit cell invasiveness, but through
      different signaling processes. In invasive, mesenchymal-like MDA-MB-231 cells,
      FFAR2 inhibits the Hippo-Yap pathway and increases expression of adhesion protein
      E-cadherin, while FFAR3 inhibits MAPK signaling. Both receptors have the net
      effect of reducing actin polymerization and invasion of cells through a Matrigel
      matrix. These effects were absent in the less invasive, epithelial-like MCF7
      cells. Correspondingly, there is reduced expression of both receptors in invasive
      breast carcinoma and in aggressive triple-negative breast tumors, relative to
      normal breast tissue. Cumulatively, our data suggest that the activation of
      cognate receptors by short chain fatty acids drives breast cancer cells toward a
      non-invasive phenotype and therefore may inhibit metastasis.

PMID- 29049320
TI  - Deconvolving sequence features that discriminate between overlapping regulatory
      annotations.
AB  - Genomic loci with regulatory potential can be annotated with various properties.
      For example, genomic sites bound by a given transcription factor (TF) can be
      divided according to whether they are proximal or distal to known promoters.
      Sites can be further labeled according to the cell types and conditions in which
      they are active. Given such a collection of labeled sites, it is natural to ask
      what sequence features are associated with each annotation label. However,
      discovering such label-specific sequence features is often confounded by overlaps
      between the labels; e.g. if regulatory sites specific to a given cell type are
      also more likely to be promoter-proximal, it is difficult to assess whether
      motifs identified in that set of sites are associated with the cell type or
      associated with promoters. In order to meet this challenge, we developed
      SeqUnwinder, a principled approach to deconvolving interpretable discriminative
      sequence features associated with overlapping annotation labels. We demonstrate
      the novel analysis abilities of SeqUnwinder using three examples. Firstly,
      SeqUnwinder is able to unravel sequence features associated with the dynamic
      binding behavior of TFs during motor neuron programming from features associated
      with chromatin state in the initial embryonic stem cells. Secondly, we
      characterize distinct sequence properties of multi-condition and cell-specific TF
      binding sites after controlling for uneven associations with promoter proximity.
      Finally, we demonstrate the scalability of SeqUnwinder to discover cell-specific
      sequence features from over one hundred thousand genomic loci that display DNase
      I hypersensitivity in one or more ENCODE cell lines.

PMID- 29049321
TI  - Determination and production of antimicrobial compounds by Aspergillus
      clavatonanicus strain MJ31, an endophytic fungus from Mirabilis jalapa L. using
      UPLC-ESI-MS/MS and TD-GC-MS analysis.
AB  - Endophytic fungi associated with medicinal plants are reported as potent
      producers of diverse classes of secondary metabolites. In the present study, an
      endophytic fungi, Aspergillus clavatonanicus strain MJ31, exhibiting significant
      antimicrobial activity was isolated from roots of Mirabilis jalapa L., was
      identified by sequencing three nuclear genes i.e. internal transcribed spacers
      ribosomal RNA (ITS rRNA), 28S ribosomal RNA (28S rRNA) and translation elongation
      factor 1- alpha (EF 1alpha). Ethyl acetate extract of strain MJ31displayed
      significant antimicrobial potential against Bacillus subtilis, followed by
      Micrococccus luteus and Staphylococcus aureus with minimum inhibitory
      concentrations (MIC) of 0.078, 0.156 and 0.312 mg/ml respectively. In addition,
      the strain was evaluated for its ability to synthesize bioactive compounds by the
      amplification of polyketide synthase (PKS) and non ribosomal peptide synthetase
      (NRPS) genes. Further, seven antibiotics (miconazole, ketoconazole, fluconazole,
      ampicillin, streptomycin, chloramphenicol, and rifampicin) were detected and
      quantified using UPLC-ESI-MS/MS. Additionally, thermal desorption-gas
      chromatography mass spectrometry (TD-GC-MS) analysis of strain MJ31 showed the
      presence of 28 volatile compounds. This is the first report on A. clavatonanicus
      as an endophyte obtained from M. jalapa. We conclude that A. clavatonanicus
      strain MJ31 has prolific antimicrobial potential against both plant and human
      pathogens and can be exploited for the discovery of new antimicrobial compounds
      and could be an alternate source for the production of secondary metabolites.

PMID- 29049322
TI  - PGC-1alpha and exercise intensity dependent adaptations in mouse skeletal muscle.
AB  - The aim of the present study was to examine the role of PGC-1alpha in intensity
      dependent exercise and exercise training-induced metabolic adaptations in mouse
      skeletal muscle. Whole body PGC-1alpha knockout (KO) and littermate wildtype (WT)
      mice performed a single treadmill running bout at either low intensity (LI) for
      40 min or moderate intensity (MI) for 20 min. Blood and quadriceps muscles were
      removed either immediately after exercise or at 3h or 6h into recovery from
      exercise and from resting controls. In addition PGC-1alpha KO and littermate WT
      mice were exercise trained at either low intensity (LIT) for 40 min or at
      moderate intensity (MIT) for 20 min 2 times pr. day for 5 weeks. In the first and
      the last week of the intervention period, mice performed a graded running
      endurance test. Quadriceps muscles were removed before and after the training
      period for analyses. The acute exercise bout elicited intensity dependent
      increases in LC3I and LC3II protein and intensity independent decrease in p62
      protein in skeletal muscle late in recovery and increased LC3II with exercise
      training independent of exercise intensity and volume in WT mice. Furthermore,
      acute exercise and exercise training did not increase LC3I and LC3II protein in
      PGC-1alpha KO. In addition, exercise-induced mRNA responses of PGC-1alpha
      isoforms were intensity dependent. In conclusion, these findings indicate that
      exercise intensity affected autophagy markers differently in skeletal muscle and
      suggest that PGC-1alpha regulates both acute and exercise training-induced
      autophagy in skeletal muscle potentially in a PGC-1alpha isoform specific manner.

PMID- 29049323
TI  - One-time versus repeated abutment connection for platform-switched implant: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: This review aims to compare peri-implant tissue changes in terms of
      clinical and radiographic aspects of implant restoration protocol using one-time
      abutment to repeated abutment connection in platform switched implant. METHOD: A
      structured search strategy was applied to three electronic databases, namely,
      Pubmed, Embase and Web of Science. Eight eligible studies, including seven
      randomised controlled studies and one controlled clinical study, were identified
      in accordance with inclusion/exclusion criteria. Outcome measures included peri
      implant bone changes (mm), peri-implant soft tissue changes (mm), probing depth
      (mm) and postsurgical complications. RESULT: Six studies were pooled for meta
      analysis on bone tissue, three for soft tissue, two for probing depth and four
      for postsurgical complications. A total of 197 implants were placed in one-time
      abutment group, whereas 214 implants were included in repeated abutment group.
      The implant systems included Global implants, Ankylos, JDEvolution (JdentalCare),
      Straumann Bone level and Conelog-Screwline. One-time abutment group showed
      significantly better outcomes than repeated abutment group, as measured in the
      standardised differences in mean values (fixed- and random-effect model):
      vertical bone change (0.41, 3.23) in 6 months, (1.51, 14.81) in 12 months and
      (2.47, 2.47) in 3 years and soft tissue change (0.21, 0.23). No significant
      difference was observed in terms of probing depth and complications. CONCLUSION:
      Our meta-analysis revealed that implant restoration protocol using one-time
      abutment is superior to repeated abutment for platform switched implant because
      of less bone resorption and soft tissue shifts in former. However, future
      randomised clinical trials should be conducted to further confirm these findings
      because of the small samples and the limited quality of the original research.

PMID- 29049324
TI  - Dynamic microbial populations along the Cuyahoga River.
AB  - The study of the microbial communities has gained traction in recent years with
      the advent of next-generation sequencing with, or without, PCR-based
      amplification of the 16S ribosomal RNA region. Such studies have been applied to
      topics as diverse as human health and environmental ecology. Fewer studies have
      investigated taxa outside of bacteria, however. We present here data
      demonstrating the utility of studying taxa outside of bacteria including algae,
      diatoms, archaea and fungi. Here, we show how location along the Cuyahoga River
      as well as a transient rainfall event heavily influence the microbial
      composition. Our data reveal how individual OTUs vary between samples and how the
      patterns of OTU abundance can accurately predict sampling location. The
      clustering of samples reveals that these taxa are all sensitive to water
      conditions in unique ways and demonstrate that, for our dataset, algae was most
      distinctive between sample groups, surpassing bacteria. Diversity between
      sampling sites could allow studies investigating pollution or water quality to
      identify marker OTUs or patterns of OTU abundance as indicators to assess
      environmental conditions or the impact of human activity. We also directly
      compare data derived from primers amplifying distinct taxa and show that taxa
      besides bacteria are excellent indicators of water condition.

PMID- 29049325
TI  - Effect of therapeutic interchange on medication reconciliation during
      hospitalization and upon discharge in a geriatric population.
AB  - BACKGROUND: Therapeutic interchange of a same class medication for an outpatient
      medication is a widespread practice during hospitalization in response to limited
      hospital formularies. However, therapeutic interchange may increase risk of
      medication errors. The objective was to characterize the prevalence and safety of
      therapeutic interchange. METHODS AND FINDINGS: Secondary analysis of a
      transitions of care study. We included patients over age 64 admitted to a
      tertiary care hospital between 2009-2010 with heart failure, pneumonia, or acute
      coronary syndrome who were taking a medication in any of six commonly
      interchanged classes on admission: proton pump inhibitors (PPIs), histamine H2
      receptor antagonists (H2 blockers), hydroxymethylglutaryl CoA reductase
      inhibitors (statins), angiotensin-converting enzyme (ACE) inhibitors, angiotensin
      receptor blockers (ARBs), and inhaled corticosteroids (ICS). There was limited
      electronic medication reconciliation support available. Main measures were
      presence and accuracy of therapeutic interchange during hospitalization, and rate
      of medication reconciliation errors on discharge. We examined charts of 303
      patients taking 555 medications at time of admission in the six medication
      classes of interest. A total of 244 (44.0%) of medications were therapeutically
      interchanged to an approved formulary drug at admission, affecting 64% of the
      study patients. Among the therapeutically interchanged drugs, we identified 78
      (32.0%) suspected medication conversion errors. The discharge medication
      reconciliation error rate was 11.5% among the 244 therapeutically interchanged
      medications, compared with 4.2% among the 311 unchanged medications (relative
      risk [RR] 2.75, 95% confidence interval [CI] 1.45-5.19). CONCLUSIONS: Therapeutic
      interchange was prevalent among hospitalized patients in this study and elevates
      the risk for potential medication errors during and after hospitalization.
      Improved electronic systems for managing therapeutic interchange and medication
      reconciliation may be valuable.

PMID- 29049326
TI  - A new machine-learning method to prognosticate paraquat poisoned patients by
      combining coagulation, liver, and kidney indices.
AB  - The prognosis of paraquat (PQ) poisoning is highly correlated to plasma PQ
      concentration, which has been identified as the most important index in PQ
      poisoning. This study investigated the predictive value of coagulation, liver,
      and kidney indices in prognosticating PQ-poisoning patients, when aligned with
      plasma PQ concentrations. Coagulation, liver, and kidney indices were first
      analyzed by variance analysis, receiver operating characteristic curves, and
      Fisher discriminant analysis. Then, a new, intelligent, machine learning-based
      system was established to effectively provide prognostic analysis of PQ-poisoning
      patients based on a combination of the aforementioned indices. In the proposed
      system, an enhanced extreme learning machine wrapped with a grey wolf
      optimization strategy was developed to predict the risk status from a pool of 103
      patients (56 males and 47 females); of these, 52 subjects were deceased and 51
      alive. The proposed method was rigorously evaluated against this real-life
      dataset, in terms of accuracy, Matthews correlation coefficients, sensitivity,
      and specificity. Additionally, the feature selection was investigated to identify
      correlating factors for risk status. The results demonstrated that there were
      significant differences in the coagulation, liver, and kidney indices between
      deceased and surviving subjects (p<0.05). Aspartate aminotransferase, prothrombin
      time, prothrombin activity, total bilirubin, direct bilirubin, indirect
      bilirubin, alanine aminotransferase, urea nitrogen, and creatinine were the most
      highly correlated indices in PQ poisoning and showed statistical significance
      (p<0.05) in predicting PQ-poisoning prognoses. According to the feature
      selection, the most important correlated indices were found to be associated with
      aspartate aminotransferase, the aspartate aminotransferase to alanine ratio,
      creatinine, prothrombin time, and prothrombin activity. The method proposed here
      showed excellent results that were better than that produced based on blood-PQ
      concentration alone. These promising results indicated that the combination of
      these indices can provide a new avenue for prognosticating the outcome of PQ
      poisoning.

PMID- 29049327
TI  - Characteristics of pulsatile flows in curved stenosed channels.
AB  - Spatial and temporal variations of the hemodynamic features occur under pulsatile
      conditions in complex vessel geometry. Wall shear stress affected by the
      disturbed flow can result in endothelial cell dysfunction, which leads to
      atherogenesis and thrombosis. Therefore, detailed understanding of the
      hemodynamic characteristics in a curved stenosed channel is highly important when
      examining the pathological effects of hemodynamic phenomena on the progression of
      atherosclerosis. The present study measures the velocity fields of pulsatile
      flows with three different Reynolds numbers in 3D curved vessel models with
      stenosis using time-resolved particle image velocimetry (PIV). Three different
      models were cast in PDMS polymer using models made by a 3D printer with different
      bend angles of 0 degrees , 10 degrees , and 20 degrees  between the longitudinal
      axes at the upstream and downstream of the stenosis. To investigate the 3D flow
      structures, a stack of 2D velocity fields was obtained by adjusting the position
      of the laser sheet along the Z-direction. The structures of flow fields in the
      stenosed models were analyzed using the distribution of the shearing strain as
      well as the skewness and full width at half maximum of the velocity profile. To
      support experiment results, distributions of pressure and 3D vortex in the curved
      stenosed channels were estimated by conducting the numerical simulation. These
      results indicate that the curvature of the tube considerably influences the
      skewness of the flow, and the shear stress is intensified near the outer
      curvature wall due to centrifugal force. The results would be helpful in
      understanding the effects of geometrical factors on plaque rupture and severe
      cardiovascular diseases.

PMID- 29049328
TI  - CA 19-9 and CA 125 as potential predictors of disease recurrence in resectable
      lung adenocarcinoma.
AB  - OBJECTIVES: Among patients who underwent primary surgery for non-small cell lung
      cancer (NSCLC), recurrent disease is frequent and cannot be accurately predicted
      solely from TNM stage and histopathological features. The aim of this study was
      to examine the association of tumor markers in pre-operative serum with recurrent
      disease. MATERIAL AND METHODS: Blood samples were collected prior to lung cancer
      surgery from 107 patients with stage I-III lung adenocarcinoma surgically treated
      at Lund University hospital, Lund, Sweden, between 2005 and 2011. The serum tumor
      markers Carcinoembryonic antigen (CEA), Neuron-specific enolase (NSE), Cancer
      antigen 125 (CA 125), Human epididymis protein 4 (HE4) and Carbohydrate antigen
      (CA 19-9) were analyzed retrospectively and clinical follow-up data were
      collected from patient charts. Forty (37%) patients were diagnosed with recurrent
      disease. RESULTS: Sixty-eight (64%) patients had at least one elevated tumor
      marker prior to surgery. In analysis of disease-free survival (DFS), CA 125
      and/or CA 19-9 were significantly associated with recurrent disease adjusted to
      stage and adjuvant treatment (hazard ratio 2.8, 95% confidence interval 1.4-5.7,
      p = 0.006). CONCLUSION: High pre-operative serum CA 19-9 and/or CA 125 might
      indicate an increased incidence of recurrent disease in resectable lung
      adenocarcinomas.

PMID- 29049329
TI  - Rural food security, subsistence agriculture, and seasonality.
AB  - Many of the world's food-insecure and undernourished people are smallholder
      farmers in developing countries. This is especially true in Africa. There is an
      urgent need to make smallholder agriculture and food systems more nutrition
      sensitive. African farm households are known to consume a sizeable part of what
      they produce at home. Less is known about how much subsistence agriculture
      actually contributes to household diets, and how this contribution changes
      seasonally. We use representative data from rural Ethiopia covering every month
      of one full year to address this knowledge gap. On average, subsistence
      production accounts for 58% of rural households' calorie consumption, that is,
      42% of the calories consumed are from purchased foods. Some seasonal variation
      occurs. During the lean season, purchased foods account for more than half of all
      calories consumed. But even during the main harvest and post-harvest season,
      purchased foods contribute more than one-third to total calorie consumption.
      Markets are even more important for dietary quality. During all seasons,
      purchased foods play a much larger role for dietary diversity than subsistence
      production. These findings suggest that strengthening rural markets needs to be a
      key element in strategies to improve food security and dietary quality in the
      African small-farm sector.

PMID- 29049330
TI  - The prevalence of human papillomavirus in oropharyngeal cancer in a New Zealand
      population.
AB  - BACKGROUND: The incidence of oropharyngeal cancer (OPC) in New Zealand (NZ) has
      more than doubled over the last 14 years with 126 cases in 2010. Overseas studies
      have shown that human papillomavirus (HPV) plays a significant role in the
      development of these cancers. However, the role of HPV in OPC and the burden on
      the NZ health system is unclear. AIM: The aim of the study was to determine the
      prevalence and the genotypes of HPV associated with OPC in New Zealand. METHODS:
      In this study, 621 OPC were identified from cancer registry data from 1996-98,
      2003-05, and 2010-12. Biopsies of 267 cases were then retrieved from laboratories
      throughout New Zealand. p16 immunohistochemistry and a human beta globin PCR were
      performed on all specimens. HPV genotyping was performed on all beta globin
      positive specimens using real-time PCR with melt analysis. RESULTS: Using a
      p16/PCR algorithm, 77.9% (95% CI: 71.1-83.5%) of cases were attributable to HPV.
      Of these, 98.5% were HPV 16 positive. There was also one case each of HPV 33 and
      35. The percentage of HPV positive cases increased from 61.9% (95% CI: 40.9%-
      79.2%) in 1996-98 to 87.5% (95% CI: 79.8%- 92.5%) in 2010-12. Results from the
      multivariable model, adjusted for sex and ethnicity found statistically
      significant associations between HPV positivity and timeframe (OR: 5.65, 95% CI:
      2.60-12.30, 2010-12 vs 1996-98), and between HPV positivity and patient age (OR:
      0.55, 95% CI: 0.33-0.99, >=61 years vs <=60 years). CONCLUSIONS: This data is
      consistent with data from other developed countries showing an increase in cases
      of HPV positive OPC in New Zealand, and the majority of cases being attributable
      to HPV 16. These results support the recent inclusion of males into the
      nationally funded immunization schedule for Gardasil(r) 9.

PMID- 29049331
TI  - HIV dynamics linked to memory CD4+ T cell homeostasis.
AB  - The dynamics of latent HIV is linked to infection and clearance of resting memory
      CD4+ T cells. Infection also resides within activated, non-dividing memory cells
      and can be impacted by antigen-driven and homeostatic proliferation despite
      suppressive antiretroviral therapy (ART). We investigated whether plasma viral
      level (pVL) and HIV DNA dynamics could be explained by HIV's impact on memory
      CD4+ T cell homeostasis. Median total, 2-LTR and integrated HIV DNA levels per
      MUL of peripheral blood, for 8 primary (PHI) and 8 chronic HIV infected (CHI)
      individuals enrolled on a raltegravir (RAL) based regimen, exhibited greatest
      changes over the 1st year of ART. Dynamics slowed over the following 2 years so
      that total HIV DNA levels were equivalent to reported values for individuals
      after 10 years of ART. The mathematical model reproduced the multiphasic dynamics
      of pVL, and levels of total, 2-LTR and integrated HIV DNA in both PHI and CHI
      over 3 years of ART. Under these simulations, residual viremia originated from
      reactivated latently infected cells where most of these cells arose from clonal
      expansion within the resting phenotype. Since virion production from clonally
      expanded cells will not be affected by antiretroviral drugs, simulations of ART
      intensification had little impact on pVL. HIV DNA decay over the first year of
      ART followed the loss of activated memory cells (120 day half-life) while the 5.9
      year half-life of total HIV DNA after this point mirrored the slower decay of
      resting memory cells. Simulations had difficulty reproducing the fast early HIV
      DNA dynamics, including 2-LTR levels peaking at week 12, and the later slow loss
      of total and 2-LTR HIV DNA, suggesting some ongoing infection. In summary, our
      modelling indicates that much of the dynamical behavior of HIV can be explained
      by its impact on memory CD4+ T cell homeostasis.

PMID- 29049332
TI  - Blue lighting accelerates post-stress relaxation: Results of a preliminary study.
AB  - Several authors have studied the influence of light on both human physiology and
      emotions. Blue light has been proved to reduce sleepiness by suppression of
      melatonin secretion and it is also present in many emotion-related studies. Most
      of these have a common lack of objective methodology since results and
      conclusions are based on subjective perception of emotions. The aim of this work
      was the objective assessment of the effect of blue lighting in post-stress
      relaxation, in comparison with white lighting, by means of bio-signals and
      standardized procedures. We conducted a study in which twelve healthy volunteers
      were stressed and then performed a relaxation session within a chromotherapy room
      with blue (test group) or white (control group) lighting. We conclude that the
      blue lighting accelerates the relaxation process after stress in comparison with
      conventional white lighting. The relaxation time decreased by approximately three
      fold (1.1 vs. 3.5 minutes). We also observed a convergence time (3.5-5 minutes)
      after which the advantage of blue lighting disappeared. This supports the
      relationship between color of light and stress, and the observations reported in
      previous works. These findings could be useful in clinical and educational
      environments, as well as in daily-life context and emerging technologies such as
      neuromarketing. However, our study must be extended to draw reliable conclusions
      and solid scientific evidence.

PMID- 29049333
TI  - Synchrotron imaging and Markov Chain Monte Carlo reveal tooth mineralization
      patterns.
AB  - The progressive character of tooth formation records aspects of mammalian life
      history, diet, seasonal behavior and climate. Tooth mineralization occurs in two
      stages: secretion and maturation, which overlap to some degree. Despite decades
      of study, the spatial and temporal pattern of elemental incorporation during
      enamel mineralization remains poorly characterized. Here we use synchrotron X-ray
      microtomography and Markov Chain Monte Carlo sampling to estimate mineralization
      patterns from an ontogenetic series of sheep molars (n = 45 M1s, 18 M2s). We
      adopt a Bayesian approach that posits a general pattern of maturation estimated
      from individual- and population-level mineral density variation over time. This
      approach converts static images of mineral density into a dynamic model of
      mineralization, and demonstrates that enamel secretion and maturation waves
      advance at nonlinear rates with distinct geometries. While enamel secretion is
      ordered, maturation geometry varies within a population and appears to be driven
      by diffusive processes. Our model yields concrete expectations for the
      integration of physiological and environmental signals, which is of particular
      significance for paleoseasonality research. This study also provides an avenue
      for characterizing mineralization patterns in other taxa. Our synchrotron imaging
      data and model are available for application to multiple disciplines, including
      health, material science, and paleontological research.

PMID- 29049334
TI  - Exams disadvantage women in introductory biology.
AB  - The gender gap in STEM fields has prompted a great deal of discussion, but what
      factors underlie performance deficits remain poorly understood. We show that
      female students underperformed on exams compared to their male counterparts
      across ten large introductory biology course sections in fall 2016 (N > 1500
      students). Females also reported higher levels of test anxiety and course
      relevant science interest. Results from mediation analyses revealed an intriguing
      pattern: for female students only, and regardless of their academic standing,
      test anxiety negatively impacted exam performance, while interest in the course
      specific science topics increased exam performance. Thus, instructors seeking
      equitable classrooms can aim to decrease test anxiety and increase student
      interest in science course content. We provide strategies for mitigating test
      anxiety and suggestions for alignment of course content with student interest,
      with the hope of successfully reimagining the STEM pathway as one that is equally
      accessible to all.

PMID- 29049335
TI  - Structural prediction of two novel human atypical SLC transporters, MFSD4A and
      MFSD9, and their neuroanatomical distribution in mice.
AB  - Out of the 430 known solute carriers (SLC) in humans, 30% are still orphan
      transporters regarding structure, distribution or function. Approximately one
      third of all SLCs belong to the evolutionary conserved and functionally diverse
      Major Facilitator Superfamily (MFS). Here, we studied the orphan proteins, MFSD4A
      and MFSD9, which are atypical SLCs of MFS type. Hidden Markov Models were used to
      identify orthologues in several vertebrates, and human MFSD4A and MFSD9 share
      high sequence identity with their identified orthologues. MFSD4A and MFSD9 also
      shared more than 20% sequence identity with other phylogenetically related SLC
      and MFSD proteins, allowing new family clustering. Homology models displayed 12
      transmembrane segments for both proteins, which were predicted to fold into a
      transporter-shaped structure. Furthermore, we analysed the location of MFSD4A and
      MFSD9 in adult mouse brain using immunohistochemistry, showing abundant neuronal
      protein staining. As MFSD4A and MFSD9 are plausible transporters expressed in
      food regulatory brain areas, we monitored transcriptional changes in several
      mouse brain areas after 24 hours food-deprivation and eight weeks of high-fat
      diet, showing that both genes were affected by altered food intake in vivo. In
      conclusion, we propose MFSD4A and MFSD9 to be novel transporters, belonging to
      disparate SLC families. Both proteins were located to neurons in mouse brain, and
      their mRNA expression levels were affected by the diet.

PMID- 29049336
TI  - Exercise as adjunctive treatment for alcohol use disorder: A randomized
      controlled trial.
AB  - AIMS: To examine whether physical activity as an adjunct to outpatient alcohol
      treatment has an effect on alcohol consumption following participation in an
      exercise intervention of six months' duration, and at 12 months after treatment
      initiation. METHODS: The study is a randomized controlled study with three arms:
      Patients allocated to (A) treatment as usual, (B) treatment as usual and
      supervised group exercise, (C) treatment as usual and individual physical
      exercise. The primary outcome measure was excessive drinking six months after
      treatment start and completion of the intervention. A logistic regression model
      was used to evaluate the odds of excessive drinking among the three groups, based
      on intention-to-treat. Changes in level of physical activity in all three groups
      were tested by using a generalized linear mixed model. A multiple linear model
      was used to test if there was an association between amount of performed physical
      activity and alcohol consumption. RESULTS: A total of 175 patients (68.6% male)
      participated. Response rates were 77.7% at six months and 57.1% at 12 months
      follow-up. OR 0.99 [95% CI: 0.46; 2.14], p = 0.976 for excessive drinking in the
      group exercise condition, and 1.02 [95% CI: 0.47; 2.18], p = 0.968 in the
      individual exercise condition, which, when compared to the control group as
      reference, did not differ statistically significantly. Participants with moderate
      level physical activity had lower odds for excessive drinking OR = 0.12 [0.05;
      0.31], p<0.001 than participants with low level physical activity. Amount of
      alcohol consumption in the intervention groups decreased by 4% [95% CI: 0.03;
      6.8], p = 0.015 for each increased exercising day. CONCLUSIONS: No direct effect
      of physical exercise on drinking outcome was found. Moderate level physical
      activity was protective against excessive drinking following treatment. A dose
      response effect of exercise on drinking outcome supports the need for
      implementing physically active lifestyles for patients in treatment for alcohol
      use disorder.

PMID- 29049337
TI  - Factors affecting pouch-related outcomes after restorative proctocolectomy.
AB  - PURPOSES: Restorative proctocolectomy (RPC) with ileal pouch anal anastomosis
      (IPAA) is the procedure of choice for patients with familial adenomatous
      polyposis (FAP) and ulcerative colitis (UC) despite morbidities that can lead to
      pouch failure. We aimed to identify factors associated with pouch-related
      morbidities. METHODS: A retrospective analysis of patients who underwent RPC with
      IPAA was performed. To investigate the factors associated with pouch-related
      morbidities, patients' preoperative demographic and clinical factors, and
      intraoperative factors were included in the analysis. RESULTS: A total of 49
      patients with UC, FAP, and colorectal cancer were included. Twenty patients
      (40.8%) experienced leakage-related, functional, and/or pouchitis-related
      morbidities. Patients with American Society of Anesthesiologists (ASA) grade 2 or
      3 had a higher risk of functional morbidity than those with grade 1.
      Intraoperative blood loss exceeding 300.0 mL was associated with an increased
      risk of pouchitis-related morbidity. CONCLUSIONS: Our study demonstrated
      associations of higher ASA grade and increased intraoperative blood loss with
      poor functional outcomes and pouchitis, respectively.

PMID- 29049338
TI  - Growing plants on oily, nutrient-poor soil using a native symbiotic fungus.
AB  - The roots of land plants associate with microbes, including fungal symbionts that
      can confer abiotic stress tolerance. Bitumen extraction following oil-sand
      surface mining in the Athabasca region of Alberta, Canada removes plant nutrients
      but leaves a petrochemical residue, making the coarse tailings (CT) hostile to
      both plants and microbes. We isolated an endophyte strain of the Ascomycete
      Trichoderma harzianum we call TSTh20-1 (hereafter, TSTh) from a dandelion that
      was naturally growing on CT. TSTh colonization allowed tomato, wheat, and
      remediation seed mixtures to germinate and their seedlings to flourish on CT
      without the use of fertilizer. Compared to control plants, TSTh increased
      germination speed, percent germination, and biomass accumulation. TSTh also
      improved plant water use efficiency and drought recovery. TSTh-colonized plants
      secreted twice the level of peroxidase into CT as did plants alone. Over two
      months, plants colonized with TSTh doubled the petrochemical mobilization from CT
      over plants alone, suggesting a peroxide-mediated mechanism for petrochemical
      degradation. TSTh grew on autoclaved CT, bitumen, and other petrochemicals as
      sole carbon sources. Further, TSTh is a micro-aerobe that could metabolize 13C
      phenanthrene to 13CO2 in 0.5% oxygen. TSTh has excellent potential for
      contributing to revegetating and remediating petrochemical contamination.

PMID- 29049339
TI  - Reliability of transcardiopulmonary thermodilution cardiac output measurement in
      experimental aortic valve insufficiency.
AB  - BACKGROUND: Monitoring cardiac output (CO) is important to optimize hemodynamic
      function in critically ill patients. The prevalence of aortic valve insufficiency
      (AI) is rising in the aging population. However, reliability of CO monitoring
      techniques in AI is unknown. The aim of this study was to investigate the impact
      of AI on accuracy, precision, and trending ability of transcardiopulmonary
      thermodilution-derived COTCPTD in comparison with pulmonary artery catheter
      thermodilution COPAC. METHODS: Sixteen anesthetized domestic pigs were subjected
      to serial simultaneous measurements of COPAC and COTCPTD. In a novel experimental
      model, AI was induced by retraction of an expanded Dormia basket in the aortic
      valve annulus. The Dormia basket was delivered via a Judkins catheter guided by
      substernal epicardial echocardiography. High (HPC), moderate (MPC) and low
      cardiac preload conditions (LPC) were induced by fluid unloading (20 ml kg-1
      blood withdrawal) and loading (subsequent retransfusion of the shed blood and
      additional infusion of 20 ml kg-1 hydroxyethyl starch). Within each preload
      condition CO was measured before and after the onset of AI. For statistical
      analysis, we used a mixed model analysis of variance, Bland-Altman analysis, the
      percentage error and concordance analysis. RESULTS: Experimental AI had a mean
      regurgitant volume of 33.6 +/- 12.0 ml and regurgitant fraction of 42.9 +/-
      12.6%. The percentage error between COTCPTD and COPAC during competent valve
      function and after induction of substantial AI was: HPC 17.7% vs. 20.0%, MPC
      20.5% vs. 26.1%, LPC 26.5% vs. 28.1% (pooled data: 22.5% vs. 24.1%). The ability
      to trend CO-changes induced by fluid loading and unloading did not differ between
      baseline and AI (concordance rate 95.8% during both conditions). CONCLUSION:
      Despite substantial AI, transcardiopulmonary thermodilution reliably measured CO
      under various cardiac preload conditions with a good ability to trend CO changes
      in a porcine model. COTCPTD and COPAC were interchangeable in substantial AI.

PMID- 29049340
TI  - Pressurized Intra Peritoneal Aerosol Chemotherapy in patients suffering from
      peritoneal carcinomatosis of pancreatic adenocarcinoma.
AB  - BACKGROUND: Patients suffering from peritoneal carcinomatosis of pancreatic
      adenocarcinoma were treated with Pressurized Intra Peritoneal Aerosol
      Chemotherapy (PIPAC), initial clinical findings are presented. METHODS: Single
      institution, tertiary referral center certified for therapy of peritoneal
      disease. Prospective data collection of PIPAC therapy with doxorubicin 1.5 mg/m2
      and cisplatin 7.5 mg/m2 of body surface delivered at intervals of six weeks. The
      outcome criteria were microscopic pathological response, survival and adverse
      events (v4.0 CTCAE). RESULTS: A total of 20 patients (m/f = 3:1) with a mean age
      of 64.9 (range: 45.0 to 87.0) years underwent 41 PIPAC procedures without
      intraoperative complications. The mean number of PIPAC cycles was 2.1 (range: one
      to four). Ten patients with >= 2 PIPAC applications were eligible for
      histological analysis to assess carcinoma regression. Complete or high grade
      tumor regression was found in two (10%) and five (25%) patients, respectively. An
      overall median survival of 36.6 weeks after the first PIPAC application was
      observed. One patient died postoperatively due to small bowel obstruction. No
      CTCAE level 3 and 4 complications occurred. CONCLUSION: In about one third of
      patients, repeated PIPAC therapy did induce histological regression of systemic
      chemo-resistant PC of pancreatic adenocarcinoma. Prospective randomized trials
      are needed to further clarify any clinical impact of such observations.

PMID- 29049341
TI  - Inhibition of early T cell cytokine production by arsenic trioxide occurs
      independently of Nrf2.
AB  - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a stress-activated
      transcription factor that induces a variety of cytoprotective genes. Nrf2 also
      mediates immunosuppressive effects in multiple inflammatory models. Upon
      activation, Nrf2 dissociates from its repressor protein, Keap1, and translocates
      to the nucleus where it induces Nrf2 target genes. The Nrf2-Keap1 interaction is
      disrupted by the environmental toxicant and chemotherapeutic agent arsenic
      trioxide (ATO). The purpose of the present study was to determine the effects of
      ATO on early events of T cell activation and the role of Nrf2 in those effects.
      The Nrf2 target genes Hmox-1, Nqo-1, and Gclc were all upregulated by ATO (1-2
      MUM) in splenocytes derived from wild-type, but not Nrf2-null, mice, suggesting
      that Nrf2 is activated by ATO in splenocytes. ATO also inhibited IFNgamma, IL-2,
      and GM-CSF mRNA and protein production in wild-type splenocytes activated with
      the T cell activator, anti-CD3/anti-CD28. However, ATO also decreased production
      of these cytokines in activated splenocytes from Nrf2-null mice, suggesting the
      inhibition is independent of Nrf2. Interestingly, ATO inhibited TNFalpha protein
      secretion, but not mRNA expression, in activated splenocytes suggesting the
      inhibition is due to post-transcriptional modification. In addition, c-Fos DNA
      binding was significantly diminished by ATO in wild-type and Nrf2-null
      splenocytes activated with anti-CD3/anti-CD28, consistent with the observed
      inhibition of cytokine production by ATO. Collectively, this study suggests that
      although ATO activates Nrf2 in splenocytes, inhibition of early T cell cytokine
      production by ATO occurs independently of Nrf2 and may instead be due to impaired
      AP-1 DNA binding.

PMID- 29049342
TI  - Association between a miRNA-146a polymorphism and susceptibility to head and neck
      squamous cell carcinoma in Chinese patients: A meta-analysis of 8 case-control
      studies.
AB  - A closer association has been found between the microRNA-146a rs2910164
      polymorphism and the risk of head and neck carcinoma in some molecular
      epidemiological studies. Recently two meta-analyses were performed to explore the
      relationship between miRNA-146a polymorphisms and the susceptibility of squamous
      cell carcinoma of the head and neck (SCCHN); however, they yielded conflicting
      results in susceptibility regarding ethnic variations. Hence, the present study
      was performed to explain the relationship between the miRNA-146a rs2910164
      polymorphism and the risk of SCCHN development of Chinese patients. We retrieved
      databases and screened eligible papers up to March 10, 2017 and then we extracted
      the essential data. The subgroup analyses were also performed based on the tumor
      site, region, and genotyping means. Crude odds ratios (OR) at 95% confidence
      intervals (CI) were chosen to describe the strength of the association. As a
      result, 6 publications were included in our study which involved 8 independent
      case-control studies. A significant association was found between miR-146a
      rs2910164 polymorphisms and the risk of SCCHN in Chinese patients according to
      the overall data [CC+CG vs. GG: OR = 1.13; 95%CI = 1.00-1.29; CC vs. GG: OR =
      1.19; 95%CI = 1.03-1.38]. According to the subgroup analysis based on tumor site,
      the risk of cancer was significantly increased among laryngeal cancer (dominant
      model: OR = 1.76, 95%CI = 1.26~2.46, P = 0.001; homozygote model: OR = 1.83,
      95%CI = 1.25~2.67, P = 0.002) and nasopharyngeal carcinoma (homozygote model: OR
      = 1.41, 95%CI = 1.05~1.90, P = 0.022). In summary, variant alleles of miR-146a
      rs2910164 alleles may have an association with the increased risk of SCCHN in
      Chinese patients, and these associations differed based on tumor site. Further
      studies including a larger sample size will be necessary to clarify these
      results.

PMID- 29049343
TI  - A sequential Monte Carlo approach to gene expression deconvolution.
AB  - High-throughput gene expression data are often obtained from pure or complex
      (heterogeneous) biological samples. In the latter case, data obtained are a
      mixture of different cell types and the heterogeneity imposes some difficulties
      in the analysis of such data. In order to make conclusions on gene expresssion
      data obtained from heterogeneous samples, methods such as microdissection and
      flow cytometry have been employed to physically separate the constituting cell
      types. However, these manual approaches are time consuming when measuring the
      responses of multiple cell types simultaneously. In addition, exposed samples, on
      many occasions, end up being contaminated with external perturbations and this
      may result in an altered yield of molecular content. In this paper, we model the
      heterogeneous gene expression data using a Bayesian framework, treating the cell
      type proportions and the cell-type specific expressions as the parameters of the
      model. Specifically, we present a novel sequential Monte Carlo (SMC) sampler for
      estimating the model parameters by approximating their posterior distributions
      with a set of weighted samples. The SMC framework is a robust and efficient
      approach where we construct a sequence of artificial target (posterior)
      distributions on spaces of increasing dimensions which admit the distributions of
      interest as marginals. The proposed algorithm is evaluated on simulated datasets
      and publicly available real datasets, including Affymetrix oligonucleotide arrays
      and national center for biotechnology information (NCBI) gene expression omnibus
      (GEO), with varying number of cell types. The results obtained on all datasets
      show a superior performance with an improved accuracy in the estimation of cell
      type proportions and the cell-type specific expressions, and in addition, more
      accurate identification of differentially expressed genes when compared to other
      widely known methods for blind decomposition of heterogeneous gene expression
      data such as Dsection and the nonnegative matrix factorization (NMF) algorithms.
      MATLAB implementation of the proposed SMC algorithm is available to download at
      https://github.com/moyanre/smcgenedeconv.git.

PMID- 29049344
TI  - Exploring the link between innate immune activation and thymic function by
      measuring sCD14 and TRECs in HIV patients living in Belgium.
AB  - Microbial translocation is now viewed as a central event in the pathogenesis of
      chronic inflammation during HIV infection. Thymic function failure is another
      crucial factor involved in HIV disease progression. The goal of this study was to
      explore the hypothesis of potential links between microbial translocation and
      thymic function in HIV-1 patients living in Belgium. The extent of microbial
      translocation was assessed through the measurement of soluble CD14 (sCD14). T
      cell receptor excision circles (sjTRECs and dbetaTRECs) were used as a measure of
      thymic function. Data were collected from 75 HIV-infected patients. Simple and
      complex linear regressions were done to analyze the link between these two
      processes. We found a statistically relevant negative correlation between
      thymopoiesis (sjTREC) and sCD14 level (p = 0.004). These results suggest a link
      between thymic function failure, microbial translocation and innate immune
      activation.

PMID- 29049345
TI  - Processing of the major autolysin of E. faecalis, AtlA, by the zinc
      metalloprotease, GelE, impacts AtlA septal localization and cell separation.
AB  - AtlA is the major peptidoglycan hydrolase of Enterococcus faecalis involved in
      cell division and cellular autolysis. The secreted zinc metalloprotease,
      gelatinase (GelE), has been identified as an important regulator of cellular
      function through post-translational modification of protein substrates. AtlA is a
      known target of GelE, and their interplay has been proposed to regulate AtlA
      function. To study the protease-mediated post-translational modification of AtlA,
      monoclonal antibodies were developed as research tools. Flow cytometry and
      Western blot analysis suggests that in the presence of GelE, surface-bound AtlA
      exists primarily as a N-terminally truncated form whereas in the absence of GelE,
      the N-terminal domain of AtlA is retained. We identified the primary GelE
      cleavage site occurring near the transition between the T/E rich Domain I and
      catalytic region, Domain II via N-terminal sequencing. Truncation of AtlA had no
      effect on the peptidoglycan hydrolysis activity of AtlA. However, we observed
      that N-terminal cleavage was required for efficient AtlA-mediated cell division
      while unprocessed AtlA was unable to resolve dividing cells into individual
      units. Furthermore, we observed that the processed AtlA has the propensity to
      localize to the cell septum on wild-type cells whereas unprocessed AtlA in the
      DeltagelE strain were dispersed over the cell surface. Combined, these results
      suggest that AtlA septum localization and subsequent cell separation can be
      modulated by a single GelE-mediated N-terminal cleavage event, providing new
      insights into the post-translation modification of AtlA and the mechanisms
      governing chaining and cell separation.

PMID- 29049346
TI  - Biological activity and dimerization state of modified phytochrome A proteins.
AB  - To assess potential physical interactions of type I phyA with the type II phyB
      phyE phytochromes in vivo, transgenes expressing fusion gene forms of phyA were
      introduced into the Arabidopsis phyA mutant background. When a single c-Myc (myc)
      epitope is added to either the N- or C-terminus of phyA, the constructs
      completely complement phyA mutant phenotypes. However, addition of larger tags,
      such as six consecutive myc epitopes or the yellow fluorescent protein sequence,
      result in fusion proteins that show reduced activity. All the tagged phyA
      proteins migrate as dimers on native gels and co-immunoprecipitation reveals no
      binding interaction of phyA to any of the type II phys in the dark or under
      continuous far-red light. Dimers of the phyA 1-615 amino acid N-terminal
      photosensory domain (NphyA), generated in vivo with a yeast GAL4 dimerization
      domain and attached to a constitutive nuclear localization sequence, are
      expressed at a low level and, although they cause a cop phenotype in darkness and
      mediate a very low fluence response to pulses of FR, have no activity under
      continuous FR. It is concluded that type I phyA in its Pr form is present in
      plants predominantly or exclusively as a homodimer and does not stably interact
      with type II phys in a dimer-to-dimer manner. In addition, its activity in
      mediating response to continuous FR is sensitive to modification of its N- or C
      terminus.

PMID- 29049347
TI  - Correlative microscopy of the constituents of a dinosaur rib fossil and hosting
      mudstone: Implications on diagenesis and fossil preservation.
AB  - We have applied correlative microscopy to identify the key constituents of a
      dorsal rib fossil from Koreanosaurus boseongensis and its hosting mudstone
      discovered at the rich fossil site in Boseong, South Korea, to investigate the
      factors that likely contributed to diagenesis and the preservation of fossil
      bone. Calcite and illite were the commonly occurring phases in the rib bone,
      hosting mudstone, and the boundary region in-between. The boundary region may
      have contributed to bone preservation once it fully formed by acting as a
      protective shell. Fluorapatite crystals in the rib bone matrix signified
      diagenetic alteration of the original bioapatite crystals. While calcite
      predominantly occupied vascular channels and cracks, platy illite crystals widely
      occupied miniscule pores throughout the bone matrix. Thorough transmission
      electron microscopy (TEM) study of illite within the bone matrix indicated the
      solid-state transformation of 1M to 2M without composition change, which was more
      evident from the lateral variation of 1M to 2M within the same layer. The high
      level of lattice disordering of 2M illite suggested an early stage of 1M to 2M
      transformation. Thus, the diagenetic alteration of both apatite and illite
      crystals within the bone matrix may have increased its overall density, as the
      preferred orientation of apatite crystals from moderate to strong degrees was
      evident despite the poor preservation of osteohistological features. The combined
      effects of rapid burial, formation of a boundary region, and diagenesis of illite
      and apatite within the bone matrix may have contributed to the rib bone
      preservation.

PMID- 29049348
TI  - Chronic administration of fluoxetine and pro-inflammatory cytokine change in a
      rat model of depression.
AB  - This study evaluated the chronic effects of fluoxetine, a commonly prescribed
      SSRI antidepressant, on the peripheral and central levels of inflammatory
      cytokines including IL-1beta, IL-6, TNF-alpha and IL-17 over a 4-interval in a
      rat model of chronic mild stress (CMS) which resembles the human experience of
      depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle
      (n = 9), CMS+fluoxetine (n = 9) and the control (n = 6) groups. Sucrose
      preference and forced swim tests were performed to assess behavioral change.
      Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine
      levels in plasma. On day 120, the brain was harvested and central level of
      cytokines was tested using Luminex. Four months of fluoxetine treatment resulted
      in changes in the sucrose preference and immobility time measurements,
      commensurate with antidepressant effects. The CMS+vehicle group exhibited
      elevated plasma levels of IL-1beta, IL-17, and TNF-alpha on day 60 or 120. Rats
      treated with fluoxetine demonstrated lower IL-1beta in plasma and brain after 90
      and 120-day treatment respectively (p<0.05). There was a trend of reduction of IL
      6 and TNF-alpha concentration. This study revealed the potential therapeutic
      effects of fluoxetine by reducing central and peripheral levels of IL-1beta in
      the alleviation of depressive symptoms.

PMID- 29049349
TI  - Effects of stand age and soil properties on soil bacterial and fungal community
      composition in Chinese pine plantations on the Loess Plateau.
AB  - The effects of Chinese pine (Pinus tabuliformis) on soil variables after
      afforestation have been established, but microbial community changes still need
      to be explored. Using high-throughput sequencing technology, we analyzed
      bacterial and fungal community composition and diversity in soils from three
      stands of different-aged, designated 12-year-old (PF1), 29-year-old (PF2), and 53
      year-old (PF3), on a Chinese pine plantation and from a natural secondary forest
      (NSF) stand that was almost 80 years old. Abandoned farmland (BL) was also
      analyzed. Shannon index values of both bacterial and fungal community in PF1 were
      greater than those in PF2, PF3 and NSF. Proteobacteria had the lowest abundance
      in BL, and the abundance increased with stand age. The abundance of
      Actinobacteria was greater in BL and PF1 soils than those in other sites. Among
      fungal communities, the dominant taxa were Ascomycota in BL and PF1 and
      Basidiomycota in PF2, PF3 and NSF, which reflected the successional patterns of
      fungal communities during the development of Chinese pine plantations. Therefore,
      the diversity and dominant taxa of soil microbial community in stands 12 and 29
      years of age appear to have undergone significant changes; afterward, the soil
      microbial community achieved a relatively stable state. Furthermore, the
      abundances of the most dominant bacterial and fungal communities correlated
      significantly with organic C, total N, C:N, available N, and available P,
      indicating the dependence of these microbes on soil nutrients. Overall, our
      findings suggest that the large changes in the soil microbial community structure
      of Chinese pine plantation forests may be attributed to the phyla present (e.g.,
      Proteobacteria, Actinobacteria, Ascomycota and Basidiomycota) which were affected
      by soil carbon and nutrients in the Loess Plateau.

PMID- 29049350
TI  - An integrative in-silico approach for therapeutic target identification in the
      human pathogen Corynebacterium diphtheriae.
AB  - Corynebacterium diphtheriae (Cd) is a Gram-positive human pathogen responsible
      for diphtheria infection and once regarded for high mortalities worldwide. The
      fatality gradually decreased with improved living standards and further
      alleviated when many immunization programs were introduced. However, numerous
      drug-resistant strains emerged recently that consequently decreased the efficacy
      of current therapeutics and vaccines, thereby obliging the scientific community
      to start investigating new therapeutic targets in pathogenic microorganisms. In
      this study, our contributions include the prediction of modelome of 13 C.
      diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins
      were identified by combining the results of pangenomics based core-genome and
      core-modelome analyses. Further, using subtractive proteomics and modelomics
      approaches for target identification, a set of 23 proteins was selected as
      essential for the bacteria. Considering human as a host, eight of these proteins
      (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983) were considered as
      essential and non-host homologs, and have been subjected to virtual screening
      using four different compound libraries (extracted from the ZINC database, plant
      derived natural compounds and Di-terpenoid Iso-steviol derivatives). The proposed
      ligand molecules showed favorable interactions, lowered energy values and high
      complementarity with the predicted targets. Our proposed approach expedites the
      selection of C. diphtheriae putative proteins for broad-spectrum development of
      novel drugs and vaccines, owing to the fact that some of these targets have
      already been identified and validated in other organisms.

PMID- 29049351
TI  - The impact of breast reduction surgery on breastfeeding: Systematic review of
      observational studies.
AB  - BACKGROUND: Almost half a million breast reduction surgeries are performed
      internationally each year, yet it is unclear how this type of surgery impacts
      breastfeeding. This is particularly important given the benefits of
      breastfeeding. OBJECTIVES: To determine if breast reduction surgery impacts
      breastfeeding success and whether different surgical techniques differentially
      impact breast feeding success. METHODS: Databases were searched up to September
      5, 2017. Studies were included if they reported the number of women successful at
      breastfeeding or lactation after breast reduction surgery, and if they reported
      either the total number of women who had children following breast reduction
      surgery, or the total number of women who attempted to breastfeed following
      surgery. RESULTS: Of 1,212 studies, 51 studies met the inclusion criteria; they
      were located worldwide and had 31 distinct breast reduction techniques. The
      percentage of breastfeeding success among studies was highly variable. However,
      when analyzed by the preservation of the column of parenchyma from the nipple
      areola complex to the chest wall (subareolar parenchyma), a clear pattern
      emerged. The median breastfeeding success was 4% (interquartile range (IQR) 0
      38%) for techniques with no preservation, compared to 75% (IQR 37-100%) for
      techniques with partial preservation and 100% (IQR 75-100%) for techniques with
      full preservation. CONCLUSIONS: Techniques that preserve the column of subareolar
      parenchyma appear to have a greater likelihood of successful breastfeeding. The
      preservation of the column of subareolar parenchyma should be disclosed to women
      prior to surgery. Guidelines on the best breast reduction techniques to be used
      in women of child bearing years may be advantageous to ensure women have the
      greatest potential for successful breastfeeding after breast reduction surgery.

PMID- 29049352
TI  - Exposure to intrauterine inflammation alters metabolomic profiles in the amniotic
      fluid, fetal and neonatal brain in the mouse.
AB  - INTRODUCTION: Exposure to prenatal inflammation is associated with diverse
      adverse neurobehavioral outcomes in exposed offspring. The mechanism by which
      inflammation negatively impacts the developing brain is poorly understood.
      Metabolomic profiling provides an opportunity to identify specific metabolites,
      and novel pathways, which may reveal mechanisms by which exposure to intrauterine
      inflammation promotes fetal and neonatal brain injury. Therefore, we investigated
      whether exposure to intrauterine inflammation altered the metabolome of the
      amniotic fluid, fetal and neonatal brain. Additionally, we explored whether
      changes in the metabolomic profile from exposure to prenatal inflammation occurs
      in a sex-specific manner in the neonatal brain. METHODS: CD-1, timed pregnant
      mice received an intrauterine injection of lipopolysaccharide (50 MUg/dam) or
      saline on embryonic day 15. Six and 48 hours later mice were sacrificed and
      amniotic fluid, and fetal brains were collected (n = 8/group). Postnatal brains
      were collected on day of life 1 (n = 6/group/sex). Global biochemical profiles
      were determined using ultra performance liquid chromatography/tandem mass
      spectrometry (Metabolon Inc.). Statistical analyses were performed by comparing
      samples from lipopolysaccharide and saline treated animals at each time point.
      For the P1 brains, analyses were stratified by sex. RESULTS/CONCLUSIONS: Exposure
      to intrauterine inflammation induced unique, temporally regulated changes in the
      metabolic profiles of amniotic fluid, fetal brain and postnatal brain. Six hours
      after exposure to intrauterine inflammation, the amniotic fluid and the fetal
      brain metabolomes were dramatically altered with significant enhancements of
      amino acid and purine metabolites. The amniotic fluid had enhanced levels of
      several members of the (hypo) xanthine pathway and this compound was validated as
      a potential biomarker. By 48 hours, the number of altered biochemicals in both
      the fetal brain and the amniotic fluid had declined, yet unique profiles existed.
      Neonatal pups exposed to intrauterine inflammation have significant alterations
      in their lipid metabolites, in particular, fatty acids. These sex-specific
      metabolic changes within the newborn brain offer an explanation regarding the
      sexual dimorphism of certain psychiatric and neurobehavioral disorders associated
      with exposure to prenatal inflammation.

PMID- 29049353
TI  - Should preventive antibiotics be used in patients with acute stroke? A systematic
      review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Infection is a common complication in acute stroke. Whether or not
      preventive antibiotics reduce the risk of infection or even lead to a favorable
      outcome and reduction of mortality after a stroke still remains equivocal. This
      review was performed to update the current knowledge on the effect and possible
      benefits of prophylactic antibiotic therapy in patients with stroke. METHODS: A
      systematic review and meta-analysis of preventive antibiotics'effect on the
      incidence of infection, favorable outcome (mRS<=2) and mortality in patients with
      acute stroke is performed with relevant randomized controlled trials. RESULTS:
      Six studies were identified, involving 4125 participants. Compared with the
      control group, the treated groups were significantly less prone to suffer from
      early overall infections [RR = 0.52, 95%CI (0.39, 0.70), p<0.0001], early
      pneumonia [RR = 0.64, 95%CI (0.42, 0.96), p = 0.03] and early urinary tract
      infections [RR = 0.35, 95%CI (0.25, 0.48), p<0.00001]. However, there was no
      significant difference in overall mortality [RR = 1.07, 95%CI (0.90, 1.27), p =
      0.44], early mortality [RR = 0.99, 95%CI (0.78, 1.26), p = 0.92], late mortality
      [RR = 1.12, 95%CI (0.94, 1.35), p = 0.21] or favorable outcome [RR = 1.00, 95%CI
      (0.92, 1.08), p = 0.98]. CONCLUSION: Although preventive antibiotic treatment did
      reduce the occurrence of early overall infections, early pneumonia and early
      urinary tract infection in patients with acute stroke, this advantage was not
      eventually translated to a favorable outcome and reduction in mortality. Future
      studies are warranted to identify any subgroup of stroke patients who might
      benefit from preventive antibiotic treatment.

PMID- 29049354
TI  - Inverse association of marijuana use with nonalcoholic fatty liver disease among
      adults in the United States.
AB  - BACKGROUND & AIMS: The impact of marijuana on nonalcoholic fatty liver disease
      (NAFLD) is largely unknown. We studied the association between marijuana and
      NAFLD utilizing cross-sectional data from the National Health and Nutrition
      Examination Survey (NHANES) from 2005-2014 and NHANES III (1988-1994). METHODS:
      Suspected NAFLD was diagnosed if serum alanine aminotransferase (ALT) was > 30
      IU/L for men and > 19 IU/L for women in the absence of other liver diseases
      (NHANES 2005-2014). In NHANES III cohort, NAFLD was defined based on
      ultrasonography. RESULTS: Of the 14,080 (NHANES 2005-2014) and 8,286 (NHANES III)
      participants, prevalence of suspected NAFLD and ultrasonographically-diagnosed
      NAFLD were inversely associated with marijuana use (p < 0.001). Compared to
      marijuana-naive participants, marijuana users were less likely to have suspected
      NAFLD (odds ratio [OR]: 0.90, 95% confidence interval [CI]: 0.82-0.99 for past
      user; OR: 0.68, 95% CI: 0.58-0.80 for current user) and ultrasonographically
      diagnosed NAFLD (OR: 0.75, 95% CI: 0.57-0.98 for current user) in the age,
      gender, ethnicity-adjusted model. On multivariate analysis, the ORs for suspected
      NAFLD comparing current light or heavy users to non-users were 0.76 (95% CI 0.58
      0.98) and 0.70 (95% CI 0.56-0.89), respectively (P for trend = 0.001) with
      similar trends in ultrasonographically-diagnosed NAFLD (OR: 0.77, 95% CI: 0.59
      1.00 for current user; OR: 0.71, 95% CI: 0.51-0.97 for current light user). In
      insulin resistance-adjusted model, marijuana use remained an independent
      predictor of lower risk of suspected NAFLD. CONCLUSIONS: In this nationally
      representative sample, active marijuana use provided a protective effect against
      NAFLD independent of known metabolic risk factors. The pathophysiology is unclear
      and warrants further investigation.

PMID- 29049355
TI  - Aberrant hepatic lipid storage and metabolism in canine portosystemic shunts.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a poorly understood multifactorial
      pandemic disorder. One of the hallmarks of NAFLD, hepatic steatosis, is a common
      feature in canine congenital portosystemic shunts. The aim of this study was to
      gain detailed insight into the pathogenesis of steatosis in this large animal
      model. Hepatic lipid accumulation, gene-expression analysis and HPLC-MS of
      neutral lipids and phospholipids in extrahepatic (EHPSS) and intrahepatic
      portosystemic shunts (IHPSS) was compared to healthy control dogs. Liver
      organoids of diseased dogs and healthy control dogs were incubated with palmitic-
      and oleic-acid, and lipid accumulation was quantified using LD540. In
      histological slides of shunt livers, a 12-fold increase of lipid content was
      detected compared to the control dogs (EHPSS P<0.01; IHPSS P = 0.042).
      Involvement of lipid-related genes to steatosis in portosystemic shunting was
      corroborated using gene-expression profiling. Lipid analysis demonstrated
      different triglyceride composition and a shift towards short chain and omega-3
      fatty acids in shunt versus healthy dogs, with no difference in lipid species
      composition between shunt types. All organoids showed a similar increase in
      triacylglycerols after free fatty acids enrichment. This study demonstrates that
      steatosis is probably secondary to canine portosystemic shunts. Unravelling the
      pathogenesis of this hepatic steatosis might contribute to a better understanding
      of steatosis in NAFLD.

PMID- 29049356
TI  - Treatment satisfaction with injectable disease-modifying therapies in patients
      with relapsing-remitting multiple sclerosis (the STICK study).
AB  - BACKGROUND: Treatment satisfaction in patients with relapsing-remitting multiple
      sclerosis (RRMS) may impact adherence and thus clinical outcomes. The objective
      of this study was to measure the satisfaction of patients with RRMS with
      injectable disease-modifying therapies (DMTs) and to evaluate the factors
      associated with treatment satisfaction. MATERIAL AND METHODS: In this
      observational retrospective study conducted in the neurology departments of 35
      hospitals throughout Spain, demographic data, disease characteristics, and
      information on treatment with injectable DMTs were collected at a single
      scheduled visit. Treatment satisfaction was assessed using the Treatment
      Satisfaction Questionnaire for Medication (TSQM), version 1.4. Patients also
      answered complementary questions about the factors that might affect treatment
      satisfaction. The data collected were analyzed descriptively. A regression model
      was used to explore the factors associated with treatment satisfaction. RESULTS:
      The study included 445 patients (mean+/-SD age, 41+/-10.2 years; two-thirds
      women). The percentages treated with each DMT were Avonex 28.5%, Rebif 44 MUg
      24.5%, Copaxone 22.5%, Betaferon 13.0%, Rebif22 MUg 8.3% and Extavia 3.1%. The
      mean+/-SD overall satisfaction according to the TSQM was 68.8+/-18.6 and the
      highest overall satisfaction was reported for Rebif 22 MUg (72.4+/-20.3) and the
      lowest for Extavia (61.7+/-23.7). In the regression analysis, rehabilitation,
      interference with social life, pain on injection and number of MS treatments
      received were significantly associated with a decrease in overall TSMQ score. A
      small but significant negative correlation was found between EDSS scores and TSMQ
      scores (rho = -0.11, p = 0.02) and effectiveness (rho = -0.17, p<0.001). A
      perceived inconvenience of injections was reflected by the stated preference of
      83% for once-daily oral treatment over other administration routes. CONCLUSIONS:
      Patients on stable injectable DMT therapy were reasonably satisfied with their
      treatment. Our results suggest that the main source of dissatisfaction with the
      current treatment is the inconvenience of the administration regimen.

PMID- 29049357
TI  - Associations of health status with subsequent blood donor behavior-An alternative
      perspective on the Healthy Donor Effect from Donor InSight.
AB  - INTRODUCTION: In donor health research, the 'Healthy Donor Effect' (HDE) often
      biases study results and hampers their interpretation. This refers to the fact
      that donors are a selected 'healthier' subset of a population due to both donor
      selection procedures and self-selection. Donors with long versus short donor
      careers, or with high versus low donation intensities are often compared to avoid
      this HDE, but underlying health differences might also cause these differences in
      behaviour. Our aim was to estimate to what extent a donor's perceived health
      status associates with donation cessation and intensity. METHODS: All active
      whole blood donors participating in Donor InSight (2007-2009; 11,107 male; 12,616
      female) were included in this prospective cohort study. We performed Cox survival
      and Poisson regression analyses to assess whether self-reported health status,
      medication use, disease diagnosed by a physician and recently having consulted a
      general practitioner (GP) or specialist were associated with (time to) donation
      cessation and donation intensity. RESULTS: At the end of 2013, 44% of the donors
      in this study had stopped donating. Donors in self-rated good health had a 15%
      lower risk to stop donating compared to donors in perceived poorer health.
      Medication use, disease diagnoses and consulting a GP were associated with a 20
      40% increased risk to stop donating and a lower donation intensity, when
      adjusting for age, number of donations and new donor status. Both men and women
      reporting good health made on average 10% more donations. CONCLUSION: Donors with
      a "good" health status were less likely to stop donating blood and tended to
      donate blood more often than donors with perceived poorer health status. This
      implies that the HDE is an important source of selection bias in studies on donor
      health and this includes studies where comparisons within donors are made. This
      HDE should be adjusted for appropriately when assessing health effects of
      donation and donors' health status may provide estimates of future donation
      behavior.

PMID- 29049358
TI  - Is the racial composition of your surroundings associated with your levels of
      social dominance orientation?
AB  - We investigate the extent to which minority group members are surrounded by
      outgroup members in their immediate environment as a predictor of social
      dominance orientation. Using a large representative sample of New Zealanders, we
      found that minority group members in outgroup dense environments reported lower
      levels of social dominance orientation (Study 1). In studies 2 and 3, Asian
      Australian and Black American participants who were surrounded by outgroup
      members reported lower social dominance orientation. For majority group (White)
      participants there was no association between social dominance orientation and
      outgroup density. Study 4 explained the overall pattern: Black Americans
      surrounded by outgroup members perceived their group to be of lower status in
      their immediate environment, and through this, reported lower social dominance
      orientation. This article adds to growing literature on contextual factors that
      predict social dominance orientation, especially among minority group members.

PMID- 29049359
TI  - Analysis of PD-1 expression in the monocyte subsets from non-septic and septic
      preterm neonates.
AB  - Programmed death-1 (PD-1) receptor system represents a part of recently reported
      immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an
      important role in downregulating the immune system proinflammatory activity.
      Until recently, PD-1 expression was not established on immune cells of the
      preterm infants. The study objectives were to confirm expression of the PD-1
      receptors on the monocytes isolated from very low birth weight newborns (VLBW),
      and to analyze their expression during the first week of life and late-onset
      sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients
      without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was
      determined on the monocyte subsets (classical, intermediate, non-classical) by
      flow cytometry. In case of late-onset sepsis (LOS), the same analysis was
      performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were
      present in all the monocyte subsets. Children, whose mothers had received
      antenatal steroids, presented higher absolute numbers of non-classical monocytes
      with PD-1 expression. Infants born extremely preterm who later developed LOS,
      initially showed a lower percentage of PD-1 receptor-positive intermediate
      monocytes in comparison to neonates born very preterm. During LOS, we observed a
      rise in the percentage of classical monocytes with PD-1 expression. In case of
      septic shock or fatal outcome, there was a higher percentage and absolute count
      of intermediate monocytes with PD-1 expression in comparison to children without
      these complications. In conclusion, monocytes from VLBW children express PD-1
      receptors. Antenatal steroid administration seems to induce PD-1 receptor
      expression in the non-classical monocytes. PD-1 might play a role in
      immunosuppressive phase of sepsis in the prematurely born children with septic
      shock and fatal outcome.

PMID- 29049360
TI  - The bacterial virulence factor CagA induces microbial dysbiosis that contributes
      to excessive epithelial cell proliferation in the Drosophila gut.
AB  - Gut microbiota facilitate many aspects of human health and development, but
      dysbiotic microbiota can promote hyperplasia and inflammation and contribute to
      human diseases such as cancer. Human patients infected with the gastric cancer
      causing bacterium Helicobacter pylori have altered microbiota; however, whether
      dysbiosis contributes to disease in this case is unknown. Many H. pylori human
      disease phenotypes are associated with a potent virulence protein, CagA, which is
      translocated into host epithelial cells where it alters cell polarity and
      manipulates host-signaling pathways to promote disease. We hypothesized that CagA
      alone could contribute to H. pylori pathogenesis by inducing microbial dysbiosis
      that promotes disease. Here we use a transgenic Drosophila model of CagA
      expression to genetically disentangle the effects of the virulence protein CagA
      from that of H. pylori infection. We found that expression of CagA within
      Drosophila intestinal stem cells promotes excess cell proliferation and is
      sufficient to alter host microbiota. Rearing CagA transgenic flies germ-free
      revealed that the dysbiotic microbiota contributes to cell proliferation
      phenotypes and also elicits expression of innate immune components, Diptericin
      and Duox. Further investigations revealed interspecies interactions are required
      for this dysbiotic CagA-dependent microbiota to promote proliferation in CagA
      transgenic and healthy control Drosophila. Our model establishes that CagA can
      alter gut microbiota and exacerbate cell proliferation and immune phenotypes
      previously attributed to H. pylori infection. This work provides valuable new
      insights into the mechanisms by which interactions between a specific virulence
      factor and the resident microbiota can contribute to the development and
      progression of disease.

PMID- 29049361
TI  - Methodological aspects of MRI of transplanted superparamagnetic iron oxide
      labeled mesenchymal stem cells in live rat brain.
AB  - In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and
      homing is vital for understanding the mechanisms of beneficial effects of MSCs
      transplantation in animal models of diseases and in clinical trials. Transplanted
      cells can be labeled with superparamagnetic iron oxide (SPIO) particles and
      visualized in vivo using a number of iron sensitive MRI techniques. However, the
      applicability of those techniques for SPIO-labeled MSCs tracking in live brain
      has not been sufficiently investigated. The goal of this study was to estimate
      the efficiency of various MRI techniques of SPIO-labeled cell tracing in the
      brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI
      (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in
      vitro and in live rat brain were for the first time compared in the same
      experiment. We have shown that SWI presents the most sensitive pulse sequence for
      SPIO-labeled MSCs MR visualization. After intracerebral administration due to
      limitations caused by local micro-hemorrhages the visualization threshold was 102
      cells, while after intra-arterial transplantation SWI permitted detection of
      several cells or even single cells. There is just one publication claiming
      detection of individual SPIO-labeled MSCs in live brain, while the other state
      much lower sensitivity, describe detection of different cell types or high
      resolution tracing of MSCs in other tissues. This study confirms the possibility
      of single cell tracing in live brain and outlines the necessary conditions. SWI
      is a method convenient for the detection of single SPIO labeled MSCs and small
      groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring
      migration and homing of transplanted cells in basic and translational
      neuroscience.

PMID- 29049362
TI  - Parallel and costly changes to cellular immunity underlie the evolution of
      parasitoid resistance in three Drosophila species.
AB  - A priority for biomedical research is to understand the causes of variation in
      susceptibility to infection. To investigate genetic variation in a model system,
      we used flies collected from single populations of three different species of
      Drosophila and artificially selected them for resistance to the parasitoid wasp
      Leptopilina boulardi, and found that survival rates increased 3 to 30 fold within
      6 generations. Resistance in all three species involves a large increase in the
      number of the circulating hemocytes that kill parasitoids. However, the different
      species achieve this in different ways, with D. melanogaster moving sessile
      hemocytes into circulation while the other species simply produce more cells.
      Therefore, the convergent evolution of the immune phenotype has different
      developmental bases. These changes are costly, as resistant populations of all
      three species had greatly reduced larval survival. In all three species
      resistance is only costly when food is in short supply, and resistance was
      rapidly lost from D. melanogaster populations when food is restricted.
      Furthermore, evolving resistance to L. boulardi resulted in cross-resistance
      against other parasitoids. Therefore, whether a population evolves resistance
      will depend on ecological conditions including food availability and the presence
      of different parasite species.

PMID- 29049363
TI  - Oxidation of beta2-glycoprotein I associates with IgG antibodies to domain I in
      patients with antiphospholipid syndrome.
AB  - Domain I (DI) of beta-2-glycoprotein I (beta2GPI) contains the immunodominant
      epitope for pathogenic antiphospholipid antibodies (aPL). DI is exposed in the
      linear form of the molecule but not in the circular form that comprises 90% of
      serum beta2GPI. The majority of circulating beta2GPI is biochemically reduced
      with two free thiols in Domain V. However, increased levels of oxidised beta2GPI
      are found in patients with antiphospholipid syndrome (APS). It is not known
      whether oxidation of beta2GPI favours the linear form of the molecule and thus
      promotes development of anti-DI antibodies. We investigated whether the
      proportion of oxidised beta2GPI associates with the presence of anti-DI in APS
      patients. Serum samples from 44 APS patients were screened for IgG, IgM and IgA
      anti-DI, anti-beta2GPI, anti-cardiolipin (anti-CL) and biochemically reduced
      beta2GPI. A negative correlation was found between the proportion of beta2GPI in
      the biochemically reduced form and IgG anti-DI levels (r = -0.54, p = 0.0002),
      but not with IgM or IgA anti-DI. Moreover, the proportion of beta2GPI in the
      reduced form was lower in IgG anti-DI positive than anti-DI negative APS patients
      (p = 0.02). The relative amount of reduced beta2GPI was no different between
      patients who were positive or negative for IgG, IgM and IgA anti-beta2GPI or anti
      CL. This study demonstrates that oxidised beta2GPI lacking free cysteine-thiol
      groups most closely associates with IgG anti-DI positivity compared to IgG anti
      CL and anti-beta2GPI. Future studies are required to ascertain the directionality
      of this association to define causation.

PMID- 29049364
TI  - Correction: Native Phytoremediation Potential of Urtica dioica for Removal of
      PCBs and Heavy Metals Can Be Improved by Genetic Manipulations Using Constitutive
      CaMV 35S Promoter.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0167927.].

PMID- 29049366
TI  - Transgenic expression of antimicrobial peptide D2A21 confers resistance to
      diseases incited by Pseudomonas syringae pv. tabaci and Xanthomonas citri, but
      not Candidatus Liberibacter asiaticus.
AB  - Citrus Huanglongbing (HLB) associated with 'Candidatus Liberibacter asiaticus'
      (Las) and citrus canker disease incited by Xanthomonas citri are the most
      devastating citrus diseases worldwide. To control citrus HLB and canker disease,
      we previously screened over forty antimicrobial peptides (AMPs) in vitro for
      their potential application in genetic engineering. D2A21 was one of the most
      active AMPs against X. citri, Agrobacterium tumefaciens and Sinorhizobium
      meliloti with low hemolysis activity. Therefore, we conducted this work to assess
      transgenic expression of D2A21 peptide to achieve citrus resistant to canker and
      HLB. We generated a construct expressing D2A21 and initially transformed tobacco
      as a model plant. Transgenic tobacco expressing D2A21 was obtained by
      Agrobacterium-mediated transformation. Successful transformation and D2A21
      expression was confirmed by molecular analysis. We evaluated disease development
      incited by Pseudomonas syringae pv. tabaci in transgenic tobacco. Transgenic
      tobacco plants expressing D2A21 showed remarkable disease resistance compared to
      control plants. Therefore, we performed citrus transformations with the same
      construct and obtained transgenic Carrizo citrange. Gene integration and gene
      expression in transgenic plants were determined by PCR and RT-qPCR. Transgenic
      Carrizo expressing D2A21 showed significant canker resistance while the control
      plants showed clear canker symptoms following both leaf infiltration and spray
      inoculation with X. citri 3213. Transgenic Carrizo plants were challenged for HLB
      evaluation by grafting with Las infected rough lemon buds. Las titer was
      determined by qPCR in the leaves and roots of transgenic and control plants.
      However, our results showed that transgenic plants expressing D2A21 did not
      significantly reduce Las titer compared to control plants. We demonstrated that
      transgenic expression of D2A21 conferred resistance to diseases incited by P.
      syringae pv. tabaci and X. citri but not Las. Our results underscore the
      difficulty in controlling HLB compared to other bacterial diseases.

PMID- 29049365
TI  - MyD88-dependent inflammasome activation and autophagy inhibition contributes to
      Ehrlichia-induced liver injury and toxic shock.
AB  - Severe hepatic inflammation is a common cause of acute liver injury following
      systemic infection with Ehrlichia, obligate Gram-negative intracellular bacteria
      that lack lipopolysaccharide (LPS). We have previously shown that type I IFN (IFN
      I) and inflammasome activation are key host-pathogenic mediators that promote
      excessive inflammation and liver damage following fatal Ehrlichia infection.
      However, the underlying signals and mechanisms that regulate protective immunity
      and immunopathology during Ehrlichia infection are not well understood. To
      address this issue, we compared susceptibility to lethal Ixodes ovatus Ehrlichia
      (IOE) infection between wild type (WT) and MyD88-deficient (MyD88-/-) mice. We
      show here that MyD88-/- mice exhibited decreased inflammasome activation,
      attenuated liver injury, and were more resistant to lethal infection than WT
      mice, despite suppressed protective immunity and increased bacterial burden in
      the liver. MyD88-dependent inflammasome activation was also dependent on
      activation of the metabolic checkpoint kinase mammalian target of rapamycin
      complex 1 (mTORC1), inhibition of autophagic flux, and defective mitophagy in
      macrophages. Blocking mTORC1 signaling in infected WT mice and primary
      macrophages enhanced bacterial replication and attenuated inflammasome
      activation, suggesting autophagy promotes bacterial replication while inhibiting
      inflammasome activation. Finally, our data suggest TLR9 and IFN-I are upstream
      signaling mechanisms triggering MyD88-mediated mTORC1 and inflammasome activation
      in macrophages following Ehrlichia infection. This study reveals that Ehrlichia
      induced liver injury and toxic shock are mediated by MyD88-dependent inflammasome
      activation and autophagy inhibition.

PMID- 29049367
TI  - The inner mantle of the giant clam, Tridacna squamosa, expresses a basolateral
      Na+/K+-ATPase alpha-subunit, which displays light-dependent gene and protein
      expression along the shell-facing epithelium.
AB  - Na+/K+-ATPase (NKA) is essential for maintaining the Na+ and K+ gradients, and
      supporting the secondary active transport of certain ions/molecules, across the
      plasma membrane of animal cells. This study aimed to clone the NKA alpha-subunit
      (NKAalpha) from the inner mantle adjacent to the extrapallial fluid of Tridacna
      squamosa, to determine its subcellular localization, and to examine the effects
      of light exposure on its transcript level and protein abundance. The cDNA coding
      sequence of NKAalpha from T. squamosa comprised 3105 bp, encoding 1034 amino
      acids with an estimated molecular mass of 114 kDa. NKAalpha had a basolateral
      localization along the shell-facing epithelium of the inner mantle. Exposure to
      12 h of light led to a significantly stronger basolateral NKAalpha
      immunofluorescence at the shell-facing epithelium, indicating that NKA might play
      a role in light-enhanced calcification in T. squamosa. After 3 h of light
      exposure, the transcript level of NKAalpha decreased transiently in the inner
      mantle, but returned to the control level thereafter. In comparison, the protein
      abundance of NKAalpha remained unchanged at hour 3, but became significantly
      higher than the control after 12 h of light exposure. Hence, the expression of
      NKAalpha in the inner mantle of T. squamosa was light-dependent. It is probable
      that a higher expression level of NKA was needed in the shell-facing epithelial
      cells of the inner mantle to cope with a rise in Na+ influx, possibly caused by
      increases in activities of some Na+-dependent ion transporters/channels involved
      in light-enhanced calcification.

PMID- 29049368
TI  - Low overlap between carbapenem resistant Pseudomonas aeruginosa genotypes
      isolated from hospitalized patients and wastewater treatment plants.
AB  - The variability of carbapenem-resistant Pseudomonas aeruginosa strains (CRPA)
      isolated from urine and respiratory samples in a large microbiological
      laboratory, serving several health care settings, and from effluents of two
      wastewater treatment plants (WWTP) from the same region was assessed by PFGE
      typing and by resistance to 10 antibiotics. During the 12-month period altogether
      213 carbapenem-resistant P. aeruginosa isolates were cultured and distributed
      into 65 pulsotypes and ten resistance profiles. For representatives of all 65
      pulsotypes 49 different MLSTs were determined. Variability of clinical and
      environmental strains was comparable, 130 carbapenem-resistant P. aeruginosa
      obtained from 109 patients were distributed into 38 pulsotypes, while 83 isolates
      from WWTPs were classified into 31 pulsotypes. Only 9 pulsotypes were shared
      between two or more settings (hospital or WWTP). Ten MLST were determined for
      those prevalent pulsotypes, two of them (ST111 and ST235) are among most
      successful CRPA types worldwide. Clinical and environmental carbapenem-resistant
      P. aeruginosa strains differed in antibiotic resistance. The highest proportion
      of clinical isolates was resistant to piperacillin/tazobactam (52.3%) and
      ceftazidime (42.3%). The highest proportion of environmental isolates was
      resistant to ceftazidime (37.1%) and ciprofloxacin (35.5%). The majority of
      isolates was resistant only to imipenem and/or meropenem. Strains with additional
      resistances were distributed into nine different patterns. All of them included
      clinically relevant strains, while environmental strains showed only four
      additional different patterns.

PMID- 29049369
TI  - Discrimination and prediction of cultivation age and parts of Panax ginseng by
      Fourier-transform infrared spectroscopy combined with multivariate statistical
      analysis.
AB  - Panax ginseng C.A. Meyer is a herb used for medicinal purposes, and its
      discrimination according to cultivation age has been an important and practical
      issue. This study employed Fourier-transform infrared (FT-IR) spectroscopy with
      multivariate statistical analysis to obtain a prediction model for discriminating
      cultivation ages (5 and 6 years) and three different parts (rhizome, tap root,
      and lateral root) of P. ginseng. The optimal partial-least-squares regression
      (PLSR) models for discriminating ginseng samples were determined by selecting
      normalization methods, number of partial-least-squares (PLS) components, and
      variable influence on projection (VIP) cutoff values. The best prediction model
      for discriminating 5- and 6-year-old ginseng was developed using tap root, vector
      normalization applied after the second differentiation, one PLS component, and a
      VIP cutoff of 1.0 (based on the lowest root-mean-square error of prediction
      value). In addition, for discriminating among the three parts of P. ginseng,
      optimized PLSR models were established using data sets obtained from vector
      normalization, two PLS components, and VIP cutoff values of 1.5 (for 5-year-old
      ginseng) and 1.3 (for 6-year-old ginseng). To our knowledge, this is the first
      study to provide a novel strategy for rapidly discriminating the cultivation ages
      and parts of P. ginseng using FT-IR by selected normalization methods, number of
      PLS components, and VIP cutoff values.

PMID- 29049370
TI  - Rebamipide protects against glaucoma eyedrop-induced ocular surface disorders in
      rabbits.
AB  - PURPOSE: This study aimed to determine if rebamipide eyedrops can improve ocular
      surface damage caused by the use of glaucoma eyedrops. METHODS: Female Kbl:Dutch
      rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one
      eye of each rabbit was untreated and the other was administered glaucoma eyedrops
      for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one
      eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the
      other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal
      and conjunctival epithelial damage was evaluated using fluorescein and rose
      bengal staining, respectively. Conjunctival inflammation was observed by light
      microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal
      microvilli were damaged) were analyzed by scanning electron microscopy. RESULTS:
      There were no significant differences in fluorescein staining between the
      untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and
      the number of inflammatory cells in the conjunctiva significantly increased after
      glaucoma eyedrop treatment. There was a four-fold increase in the number of dark
      cells in the glaucoma eyedrop-treated group compared to untreated. In contrast,
      in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal
      staining scores, the number of inflammatory cells, and the number of dark cells
      were decreased compared to the vehicle-treated glaucoma eyedrop group.
      CONCLUSIONS: Results from our in vivo rabbit study demonstrated that short-term
      use of glaucoma eyedrops induces corneal epithelium disorders at the cellular
      level, but that simultaneous use of rebamipide has the potential to protect and
      repair the ocular surface.

PMID- 29049371
TI  - Combining epidemiology with basic biology of sand flies, parasites, and hosts to
      inform leishmaniasis transmission dynamics and control.
AB  - Quantitation of the nonlinear heterogeneities in Leishmania parasites, sand fly
      vectors, and mammalian host relationships provides insights to better understand
      leishmanial transmission epidemiology towards improving its control. The parasite
      manipulates the sand fly via production of promastigote secretory gel (PSG),
      leading to the "blocked sand fly" phenotype, persistent feeding attempts, and
      feeding on multiple hosts. PSG is injected into the mammalian host with the
      parasite and promotes the establishment of infection. Animal models demonstrate
      that sand flies with the highest parasite loads and percent metacyclic
      promastigotes transmit more parasites with greater frequency, resulting in higher
      load infections that are more likely to be both symptomatic and efficient
      reservoirs. The existence of mammalian and sand fly "super-spreaders" provides a
      biological basis for the spatial and temporal clustering of clinical leishmanial
      disease. Sand fly blood-feeding behavior will determine the efficacies of indoor
      residual spraying, topical insecticides, and bed nets. Interventions need to have
      sufficient coverage to include transmission hot spots, especially in the absence
      of field tools to assess infectiousness. Interventions that reduce sand fly
      densities in the absence of elimination could have negative consequences, for
      example, by interfering with partial immunity conferred by exposure to sand fly
      saliva. A deeper understanding of both sand fly and host biology and behavior is
      essential to ensuring effectiveness of vector interventions.

PMID- 29049372
TI  - Therapeutic effect of imiquimod on dextran sulfate sodium-induced ulcerative
      colitis in mice.
AB  - BACKGROUND: Imiquimod is a Toll-like receptor-7 agonist that regulates immunity
      and can be used as an immune adjuvant. Ulcerative colitis has a close correlation
      with immune disorder. AIM: To investigate the therapeutic effect of imiquimod on
      dextran sulfate sodium (DSS)-induced colitis and explore the underlying
      mechanisms. METHODS: C57BL/6J C57 mice received 3% DSS for 7 days to induce
      ulcerative colitis. Groups of mice were intraperitoneally injected with
      dexamethasone (DXM, 1.5 mg/kg) or imiquimod (IMQ, 30 mg/kg) at the same time
      daily. During the experimental period, clinical signs, body weight, stool
      consistency and visible fecal blood were monitored and recorded daily; colitis
      was evaluated by disease activity index (DAI) score and by histological score. At
      the conclusion of the experiment, the level of colonic myeloperoxidase (MPO)
      activity and the serum levels of the cytokines tumor necrosis factor-alpha (TNF
      alpha), interleukin 6 (IL-6) and interleukin 10 (IL-10) were measured. RESULTS:
      Administration of 3% DSS for 7 days successfully induced acute colitis associated
      with diarrhea, bloody mucopurulent stool, body weight decreases, and other
      changes. Colitis severity was significantly ameliorated in the IMQ treatment
      groups, as determined by hematoxylin-eosin (HE) staining and histopathological
      scores. Moreover, IMQ significantly reduced the activity of MPO in colonic tissue
      and the serum levels of inflammatory cytokines, increased colon length and spleen
      weight, and effectively inhibited microscopic damage to the colon tissue.
      CONCLUSION: IMQ had beneficial effects on DSS-induced ulcerative colitis,
      supporting its further development and clinical application in ulcerative
      colitis.

PMID- 29049374
TI  - Correction: Age Estimation of African Lions Panthera leo by Ratio of Tooth Areas.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0153648.].

PMID- 29049373
TI  - Barcoding the butterflies of southern South America: Species delimitation
      efficacy, cryptic diversity and geographic patterns of divergence.
AB  - Because the tropical regions of America harbor the highest concentration of
      butterfly species, its fauna has attracted considerable attention. Much less is
      known about the butterflies of southern South America, particularly Argentina,
      where over 1,200 species occur. To advance understanding of this fauna, we
      assembled a DNA barcode reference library for 417 butterfly species of Argentina,
      focusing on the Atlantic Forest, a biodiversity hotspot. We tested the efficacy
      of this library for specimen identification, used it to assess the frequency of
      cryptic species, and examined geographic patterns of genetic variation, making
      this study the first large-scale genetic assessment of the butterflies of
      southern South America. The average sequence divergence to the nearest neighbor
      (i.e. minimum interspecific distance) was 6.91%, ten times larger than the mean
      distance to the furthest conspecific (0.69%), with a clear barcode gap present in
      all but four of the species represented by two or more specimens. As a
      consequence, the DNA barcode library was extremely effective in the
      discrimination of these species, allowing a correct identification in more than
      95% of the cases. Singletons (i.e. species represented by a single sequence) were
      also distinguishable in the gene trees since they all had unique DNA barcodes,
      divergent from those of the closest non-conspecific. The clustering algorithms
      implemented recognized from 416 to 444 barcode clusters, suggesting that the
      actual diversity of butterflies in Argentina is 3%-9% higher than currently
      recognized. Furthermore, our survey added three new records of butterflies for
      the country (Eurema agave, Mithras hannelore, Melanis hillapana). In summary,
      this study not only supported the utility of DNA barcoding for the identification
      of the butterfly species of Argentina, but also highlighted several cases of both
      deep intraspecific and shallow interspecific divergence that should be studied in
      more detail.

PMID- 29049375
TI  - Intratumoral heterogeneity of programmed cell death ligand-1 expression is common
      in lung cancer.
AB  - Programmed cell death ligand-1 (PD-L1) expression may predict the response to
      both programmed cell death-1 and PD-L1 inhibitors in lung cancer. However, the
      extent of intratumoral heterogeneity of PD-L1 expression, which may cause false
      negative results, is largely unexplored. We aimed to assess the intratumoral
      heterogeneity of PD-L1 expression in surgically resected lung cancer specimens by
      applying a novel method of tissue microarray, namely Spiral Arrays, which enables
      us to observe the heterogeneity in spiral-shaped tissue cores. Adenocarcinoma and
      squamous cell carcinoma specimens were obtained from consecutive patients with
      lung cancer who had undergone surgical resection at Nagasaki University Hospital
      (Nagasaki, Japan) since 2009. Small cell lung cancer and large cell carcinoma
      specimens were selected from patients in the same archive who had undergone
      resection since 1998. Spiral Arrays were constructed of spiral-shaped cores,
      prepared from representative blocks of each case, which were subjected to
      immunohistochemistry using an anti-PD-L1 antibody. Each core was divided into 8
      segments and each segment was classified as either PD-L1-positive or PD-L1
      negative using thresholds of 1.0%, 5.0%, 10.0%, and 50.0%, respectively. In
      total, 138 specimens were selected, including 60 adenocarcinomas, 59 squamous
      cell carcinomas, 12 small cell lung cancers, and 7 large cell carcinomas. The
      majority of specimens with PD-L1-positive segments exhibited heterogeneous
      expression (i.e., had a mixture of PD-L1-positive and PD-L1-negative segments
      within a core) irrespective of the threshold (1.0%, 66.7%; 5.0%, 74.4%; 10.0%,
      75.8%; and 50.0%, 85.7%]. Large variations in the ratios of PD-L1-positive
      segments were observed. At least 50.0% of the segments within a core were
      negative in no fewer than 50.0% (range, 50.0-76.0%) of cases with heterogeneous
      PD-L1 expression. In conclusion, intratumoral heterogeneity of PD-L1 expression
      was frequently observed in cases of lung cancer. Thus, multiple tumor biopsy
      specimens may be needed to accurately determine the PD-L1 expression status.

PMID- 29049376
TI  - Antioxidants and NOX1/NOX4 inhibition blocks TGFbeta1-induced CCN2 and alpha-SMA
      expression in dermal and gingival fibroblasts.
AB  - TGFbeta induces fibrogenic responses in fibroblasts. Reactive oxygen species
      (ROS)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) may
      contribute to fibrogenic responses. Here, we examine if the antioxidant N
      acetylcysteine (NAC), the NOX inhibitor diphenyleneiodonium (DPI) and the
      selective NOX1/NOX4 inhibitor GKT-137831 impairs the ability of TGFbeta to induce
      profibrotic gene expression in human gingival (HGF) and dermal (HDF) fibroblasts.
      We also assess if GKT-137831 can block the persistent fibrotic phenotype of
      lesional scleroderma (SSc) fibroblasts. We use real-time polymerase chain
      reaction and Western blot analysis to evaluate whether NAC and DPI impair the
      ability of TGFbeta1 to induce expression of fibrogenic genes in fibroblasts. The
      effects of GKT-137831 on TGFbeta-induced protein expression and the persistent
      fibrotic phenotype of lesional scleroderma (SSc) fibroblasts were tested using
      Western blot and collagen gel contraction analyses. In HDF and HGF, TGFbeta1
      induces CCN2, CCN1, endothelin-1 and alpha-smooth muscle actin (SMA) in a fashion
      sensitive to NAC. Induction of COL1A1 mRNA was unaffected. Similar results were
      seen with DPI. NAC and DPI impaired the ability of TGFbeta1 to induce protein
      expression of CCN2 and alpha-SMA in HDF and HGF. GKT-137831 impaired TGFbeta
      induced CCN2 and alpha-SMA protein expression in HGF and HDF. In lesional SSc
      dermal fibroblasts, GKT-137831 reduced alpha-SMA and CCN2 protein overexpression
      and collagen gel contraction. These results are consistent with the hypothesis
      that antioxidants or NOX1/4 inhibition may be useful in blocking profibrotic
      effects of TGFbeta on dermal and gingival fibroblasts and warrant consideration
      for further development as potential antifibrotic agents.

PMID- 29049377
TI  - Truncated hemoglobin 1 is a new player in Chlamydomonas reinhardtii acclimation
      to sulfur deprivation.
AB  - Truncated hemoglobins constitute a large family, present in bacteria, in archaea
      and in eukaryotes. However, a majority of physiological functions of these
      proteins remains to be elucidated. Identification and characterization of a novel
      role of truncated hemoglobins in the model alga provides a framework for a more
      complete understanding of their biological functions. Here, we use quantitative
      RT-PCR to show that three truncated hemoglobins of Chlamydomonas reinhardtii,
      THB1, THB2 and THB12, are induced under conditions of depleted sulfur (S) supply.
      THB1 underexpression results in the decrease in cell size, as well in levels of
      proteins, chlorophylls and mRNA of several S-responsive genes under S starvation.
      We provide evidence that knock-down of THB1 enhances NO production under S
      deprivation. In S-deprived cells, a subset of S limitation-responsive genes is
      controlled by NO in THB1-dependent pathway. Moreover, we demonstrate that
      deficiency for S represses the nitrate reduction and that THB1 is involved in
      this control. Thus, our data support the idea that in S-deprived cells THB1 plays
      a dual role in NO detoxification and in coordinating sulfate limitation with
      nitrate assimilation. This study uncovers a new function for the Chlamydomonas
      reinhardtii THB1 in the control of proper response to S deprivation.

PMID- 29049378
TI  - Immune-modulatory genomic properties differentiate gut microbiota of infants with
      and without eczema.
AB  - Gut microbiota play an important role in human immunological processes,
      potentially affecting allergic diseases such as eczema. The diversity and
      structure of gut microbiota in infants with eczema have been previously
      documented. This study aims to evaluate by comparative metagenomics differences
      in genetic content in gut microbiota of infants with eczema and their matched
      controls. Stools were collected at the age of one month old from twelve infants
      from an at risk birth cohort in a case control manner. Clinical follow up for
      atopic outcomes were carried out at the age of 12 and 24 months. Microbial
      genomic DNA were extracted from stool samples and used for shotgun sequencing.
      Comparative metagenomic analysis showed that immune-regulatory TCAAGCTTGA motifs
      were significantly enriched in the six healthy controls (C) communities compared
      to the six eczema subjects (E), with many encoded by Bifidobacterium (38% of the
      total motifs in the C communities). Draft genomes of five Bifidobacterium species
      populations (B. longum, B. bifidum, B. breve, B. dentium, and B.
      pseudocatenulatum) were recovered from metagenomic datasets. The B. longum BFN
      121-2 genome encoded more TCAAGCTTGA motifs (4.2 copies per one million genome
      sequence) than other Bifidobacterium genomes. Additionally, the communities in
      the stool of controls (C) were also significantly enriched in functions
      associated with tetrapyrrole biosynthesis compared to those of eczema (E). Our
      results show distinct immune-modulatory genomic properties of gut microbiota in
      infants associated with eczema and provide new insights into potential role of
      gut microbiota in affecting human immune homeostasis.

PMID- 29049379
TI  - Mathematical model of early Reelin-induced Src family kinase-mediated signaling.
AB  - Reelin is a large glycoprotein with a dual role in the mammalian brain. It
      regulates the positioning and differentiation of postmitotic neurons during brain
      development and modulates neurotransmission and memory formation in the adult
      brain. Alterations in the Reelin signaling pathway have been described in
      different psychiatric disorders. Reelin mainly signals by binding to the
      lipoprotein receptors Vldlr and ApoER2, which induces tyrosine phosphorylation of
      the adaptor protein Dab1 mediated by Src family kinases (SFKs). In turn,
      phosphorylated Dab1 activates downstream signaling cascades, including PI3-kinase
      dependent signaling. In this work, a mechanistic model based on ordinary
      differential equations was built to model early dynamics of the Reelin-mediated
      signaling cascade. Mechanistic models are frequently used to disentangle the
      highly complex mechanisms underlying cellular processes and obtain new biological
      insights. The model was calibrated on time-resolved data and a dose-response
      measurement of protein concentrations measured in cortical neurons treated with
      Reelin. It focusses on the interplay between Dab1 and SFKs with a special
      emphasis on the tyrosine phosphorylation of Dab1, and their role for the
      regulation of Reelin-induced signaling. Model selection was performed on
      different model structures and a comprehensive mechanistic model of the early
      Reelin signaling cascade is provided in this work. It emphasizes the importance
      of Reelin-induced lipoprotein receptor clustering for SFK-mediated Dab1 trans
      phosphorylation and does not require co-receptors to describe the measured data.
      The model is freely available within the open-source framework Data2Dynamics
      (www.data2dynamics.org). It can be used to generate predictions that can be
      validated experimentally, and provides a platform for model extensions both to
      downstream targets such as transcription factors and interactions with other
      transmembrane proteins and neuronal signaling pathways.

PMID- 29049380
TI  - Persistent smoking after a cardiovascular event: A nationwide retrospective study
      in Korea.
AB  - Smoking is a major risk factor of cardiovascular disease (CVD) such as stroke and
      ischemic heart disease. Prior studies have observed people continued smoking even
      after being diagnosed with CVD. However, population-level data regarding smoking
      behavior changes among people who are diagnosed with CVD are still lacking. From
      the National Health Insurance sample cohort database, we identified 1,700
      patients diagnosed as having CVD between 2003 and 2012, and underwent the
      national health screening examination in the year before and after the CVD event.
      We found that 486 (28.6%) were smokers before the CVD event. Among them, 240
      (49.4%) continued to smoke despite the diagnosis. We observed that a higher
      smoking amount and longer smoking duration before the diagnosis were associated
      with persistent smoking. Our finding that approximately 50% of smokers continue
      smoking even after CVD events supports the need for an assessment of patients'
      smoking statuses during follow-up after a CVD event and for health-care providers
      to offer the appropriate smoking cessation interventions to those who continue
      smoking.

PMID- 29049382
TI  - Reaching the end of the line: Operational issues with implementing phone-based
      unannounced pill counts in resource-limited settings.
AB  - INTRODUCTION: Accurate measurement of adherence is necessary to ensure that
      therapeutic outcomes can be attributed to the recommended treatment. Phone-based
      unannounced pill counts were shown to be feasible and reliable measures of
      adherence in developed settings; and have been further used as part of medication
      adherence interventions. However, it is not clear whether this method can be
      implemented successfully in resource-limited settings, where cellular network and
      mobile phone coverage may be low. Our objective is to describe operational issues
      surrounding the use of phone-based unannounced pill counts in Lesotho and
      Ethiopia. METHODS: Phone-based monthly unannounced pill counts, using an
      adaptation of a standardized protocol from previous US-based studies, were
      utilized to measure anti-TB and antiretroviral medication adherence in two
      implementation science studies in resource-limited settings, START (Lesotho) and
      ENRICH (Ethiopia). RESULTS: In START, 19.6% of calls were completed, with 71.9%
      of participants reached at least once; majority of failed call attempts were due
      to phones not being available (54.8%) or because participants were away from the
      pills (32.7%). In ENRICH, 33.5% of calls were completed, with 86.7% of
      participants reached at least once; the main reasons for failed call attempts
      were phones being switched off (31.5%), participants not answering (27.3%),
      participants' discomfort speaking on the phone (15.4%), and network problems
      (13.2%). Structural, facility-level, participant-level, and data collection
      challenges were encountered in these settings. DISCUSSION: Phone-based
      unannounced pill counts were found to be challenging, and response rates
      suboptimal. While some of these challenges were specific to local contexts, most
      of them are generalizable to resource-limited settings. In a research study
      context, a possible solution to ease operational challenges may be to focus phone
      based unannounced pill count efforts on a randomly selected sample from
      participants who are provided with study phones and rigorously ensure that call
      attempts are made for these participants.

PMID- 29049381
TI  - A structural equation model of the relationship between insomnia, negative
      affect, and paranoid thinking.
AB  - BACKGROUND: A growing body of evidence points to relationships between insomnia,
      negative affect, and paranoid thinking. However, studies are needed to examine
      (i) whether negative affect mediates the relation between insomnia and paranoid
      thinking, (ii) whether different types of insomnia exert different effects on
      paranoia, and (iii) to compare the impact of objective and self-reported sleeping
      difficulties. METHOD: Structural equation modelling was therefore used to test
      competing models of the relationships between self-reported insomnia, negative
      affect, and paranoia. n = 348 participants completed measures of insomnia,
      negative affect and paranoia. A subset of these participants (n = 91) went on to
      monitor their sleep objectively (using a portable sleep monitor made by Zeo) for
      seven consecutive nights. Associations between objectively recorded sleep,
      negative affect, and paranoia were explored using linear regression. RESULTS: The
      findings supported a fully mediated model where self-reported delayed sleep
      onset, but not self-reported problems with sleep maintenance or objective
      measures of sleep, was directly associated with negative affect that, in turn,
      was associated with paranoia. There was no evidence of a direct association
      between delayed sleep onset or sleep maintenance problems and paranoia.
      CONCLUSIONS: Taken together, the findings point to an association between
      perceived (but not objective) difficulties initially falling asleep (but not
      maintaining sleep) and paranoid thinking; a relationship that is fully mediated
      by negative affect. Future research should seek to disentangle the causal
      relationships between sleep, negative affect, and paranoia (e.g., by examining
      the effect of an intervention using prospective designs that incorporate
      experience sampling). Indeed, interventions might profitably target (i) perceived
      sleep quality, (ii) sleep onset, and / or (iii) emotion regulation as a route to
      reducing negative affect and, thus, paranoid thinking.

PMID- 29049383
TI  - Lutein accumulates in subcellular membranes of brain regions in adult rhesus
      macaques: Relationship to DHA oxidation products.
AB  - OBJECTIVES: Lutein, a carotenoid with anti-oxidant functions, preferentially
      accumulates in primate brain and is positively related to cognition in humans.
      Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), is also
      beneficial for cognition, but is susceptible to oxidation. The present study
      characterized the membrane distribution of lutein in brain regions important for
      different domains of cognitive function and determined whether membrane lutein
      was associated with brain PUFA oxidation. METHODS: Adult rhesus monkeys were fed
      a stock diet (~2 mg/day lutein or ~0.5 MUmol/kg body weight/day) (n = 9) or the
      stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 MUmol/kg body
      weight/day) and zeaxanthin (~0.5 mg/day or 0.1 MUmol/kg body weight/day) for 6-12
      months (n = 4). Nuclear, myelin, mitochondrial, and neuronal plasma membranes
      were isolated using a Ficoll density gradient from prefrontal cortex (PFC),
      cerebellum (CER), striatum (ST), and hippocampus (HC). Carotenoids, PUFAs, and
      PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively.
      RESULTS: All-trans-lutein (ng/mg protein) was detected in all regions and
      membranes and was highly variable among monkeys. Lutein/zeaxanthin
      supplementation significantly increased total concentrations of lutein in serum,
      PFC and CER, as well as lutein in mitochondrial membranes and total DHA
      concentrations in PFC only (P<0.05). In PFC and ST, mitochondrial lutein was
      inversely related to DHA oxidation products, but not those from arachidonic acid
      (P <0.05). DISCUSSION: This study provides novel data on subcellular lutein
      accumulation and its relationship to DHA oxidation in primate brain. These
      findings support the hypothesis that lutein may be associated with antioxidant
      functions in the brain.

PMID- 29049384
TI  - Ideal cardiovascular health predicts lower risk of abnormal liver enzymes levels
      in the Chilean National Health Survey (2009-2010).
AB  - High levels of gamma glutamyltransferase (gamma-GT) and alanine aminotransferase
      (ALT), as well as fatty liver index (FLI) has been associated with higher
      cardiovascular disease risk factors in adults. The aim of this study was to
      examine the relationship between gamma-GT, ALT, and fatty liver index FLI levels
      across a gradient number of ideal cardiovascular health metrics in a
      representative sample of adults from the Chilean National Health Survey 2009
      2010. Data from 1,023 men and 1,449 women (>= 15 years) from the Chilean Health
      Survey 2009-2010 were analyzed. Ideal cardiovascular health was defined as
      meeting ideal levels of the following components: four behaviours (smoking, body
      mass index, physical activity and diet adherence) and three factors (total
      cholesterol, blood pressure and fasting glucose). Adults were grouped into three
      categories according to their number of ideal cardiovascular health metrics:
      ideal (5-7 metrics), intermediate (3-4 metrics), and poor (0-2 metrics). Blood
      levels of gamma-GT and ALT were measured and the FLI was calculated. A higher
      number of ideal cardiovascular health index metric was associated with lower
      gamma-GT, ALT and FLI (p from trend analysis <0.001). Also, adults meeting at
      least 3-4 metrics were predicted less likely to have prevalence of abnormal
      levels of gamma-GT and FLI (p<0.001) compared to adults who met only 0-2 metrics.
      These findings reinforce the usefulness of the ideal cardiovascular health
      metrics proposed by the American Heart Association as a tool to identify target
      subjects and promote cardiovascular health in South-American adults.

PMID- 29049385
TI  - Correction: Short-term in situ shading effectively mitigates linear progression
      of coral-killing sponge Terpios hoshinota.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182365.].

PMID- 29049386
TI  - Reversible differentiation of immortalized human bladder smooth muscle cells
      accompanied by actin bundle reorganization.
AB  - Previous studies have shown that phenotypic modulation of smooth muscle cells
      (SMCs) plays a pivotal role in human diseases. However, the molecular mechanisms
      underlying the reversible differentiation of SMCs remain elusive particularly
      because cultured SMCs that reproducibly exhibit bidirectional phenotypic
      modulation have not been established. Here we established an immortalized human
      bladder SMC line designated as hBS11. Under differentiation-inducing conditions,
      hBS11 cells underwent smooth muscle differentiation accompanied by the robust
      expression of smooth muscle differentiation markers and isoform-dependent
      reorganization of actin bundles. The cholinergic receptor agonist carbachol
      increased intracellular calcium in differentiated hBS11 cells in an acetylcholine
      muscarinic receptor-dependent manner. Differentiated hBS11 cells displayed
      contractile properties depending on the elevation in the levels of intracellular
      calcium. Depolarization of membrane potential triggered inward sodium current in
      differentiated hBS11 cells. However, differentiated hBS11 cells lost the
      differentiated phenotype and resumed mitosis when re-fed with growth medium. Our
      study provides direct evidence pertaining to the human bladder SMCs being able to
      retain the capacity of reversible differentiation and that the reorganization of
      actin bundles is involved in the reinstatement of contractility. Moreover, we
      have established a human SMC line retaining high proliferating potential without
      compromising differentiation potential.

PMID- 29049387
TI  - Quantifying the strength of quorum sensing crosstalk within microbial
      communities.
AB  - In multispecies microbial communities, the exchange of signals such as acyl
      homoserine lactones (AHL) enables communication within and between species of
      Gram-negative bacteria. This process, commonly known as quorum sensing, aids in
      the regulation of genes crucial for the survival of species within heterogeneous
      populations of microbes. Although signal exchange was studied extensively in well
      mixed environments, less is known about the consequences of crosstalk in
      spatially distributed mixtures of species. Here, signaling dynamics were measured
      in a spatially distributed system containing multiple strains utilizing
      homologous signaling systems. Crosstalk between strains containing the lux, las
      and rhl AHL-receptor circuits was quantified. In a distributed population of
      microbes, the impact of community composition on spatio-temporal dynamics was
      characterized and compared to simulation results using a modified reaction
      diffusion model. After introducing a single term to account for crosstalk between
      each pair of signals, the model was able to reproduce the activation patterns
      observed in experiments. We quantified the robustness of signal propagation in
      the presence of interacting signals, finding that signaling dynamics are largely
      robust to interference. The ability of several wild isolates to participate in
      AHL-mediated signaling was investigated, revealing distinct signatures of
      crosstalk for each species. Our results present a route to characterize crosstalk
      between species and predict systems-level signaling dynamics in multispecies
      communities.

PMID- 29049388
TI  - An inducible mouse model of podocin-mutation-related nephrotic syndrome.
AB  - Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic
      syndrome. The most common podocin mutation, R138Q, is associated with early
      disease onset and rapid progression to end-stage renal disease. Knock-in mice
      carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental
      arrest of podocytes and lethal renal failure at neonatal age. Here we created a
      conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen
      inducible Cre recombinase, which permits to study the effects of the mutation in
      postnatal life. Within the first week of R140Q hemizygosity induction the animals
      developed proteinuria, which peaked after 4-5 weeks. Subsequently the animals
      developed progressive renal failure, with a median survival time of 12 (95% CI:
      11-13) weeks. Foot process fusion was observed within one week, progressing to
      severe and global effacement in the course of the disease. The number of
      podocytes per glomerulus gradually diminished to 18% compared to healthy controls
      12-16 weeks after induction. The fraction of segmentally sclerosed glomeruli was
      25%, 85% and 97% at 2, 4 and 8 weeks, respectively. Severe tubulointerstitial
      fibrosis was present at later disease stage and was correlated quantitatively
      with the level of proteinuria at early disease stages. While R140Q podocin mRNA
      expression was elevated, protein abundance was reduced by more than 50% within
      one week following induction. Whereas miRNA21 expression persistently increased
      during the first 4 weeks, miRNA-193a expression peaked 2 weeks after induction.
      In conclusion, the inducible R140Q-podocin mouse model is an auspicious model of
      the most common genetic cause of human nephrotic syndrome, with a spontaneous
      disease course strongly reminiscent of the human disorder. This model constitutes
      a valuable tool to test the efficacy of novel pharmacological interventions aimed
      to improve podocyte function and viability and attenuate proteinuria,
      glomerulosclerosis and progressive renal failure.

PMID- 29049389
TI  - Endemic chronic wasting disease causes mule deer population decline in Wyoming.
AB  - Chronic wasting disease (CWD) is a fatal transmissible spongiform encephalopathy
      affecting white-tailed deer (Odocoileus virginianus), mule deer (Odocoileus
      hemionus), Rocky Mountain elk (Cervus elaphus nelsoni), and moose (Alces alces
      shirasi) in North America. In southeastern Wyoming average annual CWD prevalence
      in mule deer exceeds 20% and appears to contribute to regional population
      declines. We determined the effect of CWD on mule deer demography using age
      specific, female-only, CWD transition matrix models to estimate the population
      growth rate (lambda). Mule deer were captured from 2010-2014 in southern Converse
      County Wyoming, USA. Captured adult (>= 1.5 years old) deer were tested ante
      mortem for CWD using tonsil biopsies and monitored using radio telemetry. Mean
      annual survival rates of CWD-negative and CWD-positive deer were 0.76 and 0.32,
      respectively. Pregnancy and fawn recruitment were not observed to be influenced
      by CWD. We estimated lambda = 0.79, indicating an annual population decline of
      21% under current CWD prevalence levels. A model derived from the demography of
      only CWD-negative individuals yielded; lambda = 1.00, indicating a stable
      population if CWD were absent. These findings support CWD as a significant
      contributor to mule deer population decline. Chronic wasting disease is difficult
      or impossible to eradicate with current tools, given significant environmental
      contamination, and at present our best recommendation for control of this disease
      is to minimize spread to new areas and naive cervid populations.

PMID- 29049390
TI  - Do two and three year old children use an incremental first-NP-as-agent bias to
      process active transitive and passive sentences?: A permutation analysis.
AB  - We used eye-tracking to investigate if and when children show an incremental bias
      to assume that the first noun phrase in a sentence is the agent (first-NP-as
      agent bias) while processing the meaning of English active and passive transitive
      sentences. We also investigated whether children can override this bias to
      successfully distinguish active from passive sentences, after processing the
      remainder of the sentence frame. For this second question we used eye-tracking
      (Study 1) and forced-choice pointing (Study 2). For both studies, we used a
      paradigm in which participants simultaneously saw two novel actions with reversed
      agent-patient relations while listening to active and passive sentences. We
      compared English-speaking 25-month-olds and 41-month-olds in between-subjects
      sentence structure conditions (Active Transitive Condition vs. Passive
      Condition). A permutation analysis found that both age groups showed a bias to
      incrementally map the first noun in a sentence onto an agent role. Regarding the
      second question, 25-month-olds showed some evidence of distinguishing the two
      structures in the eye-tracking study. However, the 25-month-olds did not
      distinguish active from passive sentences in the forced choice pointing task. In
      contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent
      bias to the extent that they clearly distinguished between active and passive
      sentences both in the eye-tracking data and in the pointing task. The results are
      discussed in relation to the development of syntactic (re)parsing.

PMID- 29049391
TI  - Modelling individual tree height to crown base of Norway spruce (Picea abies (L.)
      Karst.) and European beech (Fagus sylvatica L.).
AB  - Height to crown base (HCB) of a tree is an important variable often included as a
      predictor in various forest models that serve as the fundamental tools for
      decision-making in forestry. We developed spatially explicit and spatially
      inexplicit mixed-effects HCB models using measurements from a total 19,404 trees
      of Norway spruce (Picea abies (L.) Karst.) and European beech (Fagus sylvatica
      L.) on the permanent sample plots that are located across the Czech Republic.
      Variables describing site quality, stand density or competition, and species
      mixing effects were included into the HCB model with use of dominant height
      (HDOM), basal area of trees larger in diameters than a subject tree (BAL-
      spatially inexplicit measure) or Hegyi's competition index (HCI-spatially
      explicit measure), and basal area proportion of a species of interest (BAPOR),
      respectively. The parameters describing sample plot-level random effects were
      included into the HCB model by applying the mixed-effects modelling approach.
      Among several functional forms evaluated, the logistic function was found most
      suited to our data. The HCB model for Norway spruce was tested against the data
      originated from different inventory designs, but model for European beech was
      tested using partitioned dataset (a part of the main dataset). The variance
      heteroscedasticity in the residuals was substantially reduced through inclusion
      of a power variance function into the HCB model. The results showed that
      spatially explicit model described significantly a larger part of the HCB
      variations [R2adj = 0.86 (spruce), 0.85 (beech)] than its spatially inexplicit
      counterpart [R2adj = 0.84 (spruce), 0.83 (beech)]. The HCB increased with
      increasing competitive interactions described by tree-centered competition
      measure: BAL or HCI, and species mixing effects described by BAPOR. A test of the
      mixed-effects HCB model with the random effects estimated using at least four
      trees per sample plot in the validation data confirmed that the model was precise
      enough for the prediction of HCB for a range of site quality, tree size, stand
      density, and stand structure. We therefore recommend measuring of HCB on four
      randomly selected trees of a species of interest on each sample plot for
      localizing the mixed-effects model and predicting HCB of the remaining trees on
      the plot. Growth simulations can be made from the data that lack the values for
      either crown ratio or HCB using the HCB models.

PMID- 29049392
TI  - Multiple co-clustering based on nonparametric mixture models with heterogeneous
      marginal distributions.
AB  - We propose a novel method for multiple clustering, which is useful for analysis
      of high-dimensional data containing heterogeneous types of features. Our method
      is based on nonparametric Bayesian mixture models in which features are
      automatically partitioned (into views) for each clustering solution. This feature
      partition works as feature selection for a particular clustering solution, which
      screens out irrelevant features. To make our method applicable to high
      dimensional data, a co-clustering structure is newly introduced for each view.
      Further, the outstanding novelty of our method is that we simultaneously model
      different distribution families, such as Gaussian, Poisson, and multinomial
      distributions in each cluster block, which widens areas of application to real
      data. We apply the proposed method to synthetic and real data, and show that our
      method outperforms other multiple clustering methods both in recovering true
      cluster structures and in computation time. Finally, we apply our method to a
      depression dataset with no true cluster structure available, from which useful
      inferences are drawn about possible clustering structures of the data.

PMID- 29049393
TI  - Social hierarchy modulates responses of fish exposed to contaminants of emerging
      concern.
AB  - Many organisms, including the fathead minnow (Pimephales promelas), a
      toxicological model organism, establish social hierarchies. The social rank of
      each male in a population is under the control of the hypothalamic-pituitary
      gonadal (HPG) axis mainly through regulation of circulating androgen
      concentrations, which in turn drive the expression of secondary sex
      characteristics (SSCs). As dominant and subordinate males in an exposure study
      are initially under different physiological conditions (i.e., differing plasma
      androgen concentrations), we proposed that they belong to different
      subpopulations in the context of exposure to compounds that may interact with the
      HPG axis. Using a meta-analysis of our data from several previously published
      studies, we corroborated the hypothesis that social status, as indicated by SSCs,
      results in distinct clusters (eigenvalues >0.8 explaining >80% of variability)
      with differential expression of plasma vitellogenin, a commonly used biomarker of
      exposure to contaminants of emerging concern (CEC). Furthermore, we confirmed our
      predictions that exposure to estrogenic CECs would homogenize plasma vitellogenin
      response (E1: cluster mean SSC values decreased to 4.33 and 4.86 relative to
      those of control; E2: decreased to 4.8 and 5.37) across the social hierarchy. In
      contrast, serotonin-specific reuptake inhibitors expand this response range
      (cluster mean SSC increased to 5.21 and 6.5 relative to those of control). Our
      results demonstrated that social hierarchies in male fathead minnows result in
      heterogeneous responses to chemical exposure. These results represent a
      cautionary note for the experimental design of single-sex exposure studies. We
      anticipate our study to be a starting point for the re-evaluation of
      toxicological data analyses in single sex exposure experiments.

PMID- 29049394
TI  - Electrical impedance myography detects age-related muscle change in mice.
AB  - Loss of muscle mass and strength represents one of the most significant
      contributors to impaired function in older adults. Convenient and non-invasive
      biomarkers are needed that can readily identify and track age-related muscle
      change. Previous data has suggested electrical impedance myography (EIM) has the
      potential to serve in this capacity. In this study we investigated how changes in
      EIM compared with other standard measures of muscle structure and function in
      aged compared with young mice. A total of 19 male mice aged approximately 25
      months and 19 male mice aged 3 months underwent surface multifrequency EIM of the
      right gastrocnemius muscle using standard methods. Fore and hind limb grip
      strength, sciatic compound muscle action potential amplitude, and in-situ force
      of the gastrocnemius were also measured; after sacrifice, gastrocnemius myofiber
      size was assessed using standard histology. Spearman correlation coefficients
      were calculated to investigate the association between EIM and muscle
      characteristics. EIM in aged animals demonstrated significantly lower 50 kHz
      impedance phase (p<0.001) and reactance (p<0.01) values as well as reduced
      multifrequency parameters. In contrast, absolute gastrocnemius muscle mass was no
      different between young and aged mice (p = 0.58) but was reduced in aged mice
      after normalization to body mass (p<0.001). Median myofiber size in the aged mice
      was not different from that of young mice (p = 0.72). Aged mice showed reduced
      muscle function on the basis of normalized fore limb (p<0.001) and normalized
      hind limb (p<0.001) grip strength, as well as normalized gastrocnemius twitch
      (p<0.001) and normalized maximal isometric force (p<0.001). Sciatic compound
      muscle action potential amplitude was reduced in aged mice (p<0.05). EIM
      parameters showed good correlation with reduced standard physiological and
      electrophysiological measures of muscle health. Our study suggests that EIM is
      sensitive to aged-related muscle change and may represent a convenient and
      valuable method of quantifying loss of muscle health.

PMID- 29049395
TI  - Guidelines for morpholino use in zebrafish.

PMID- 29049396
TI  - Improved data validity in the Swedish Register of Palliative Care.
AB  - INTRODUCTION: The Swedish Register of Palliative Care (SRPC) is a national
      quality register that collects data about end-of-life care from healthcare
      providers that care for dying patients. Data are used for quality control and
      research. Data are mainly collected with an end-of-life questionnaire (ELQ),
      which is completed by healthcare staff after the death of a patient. A previous
      validity assessment of the ELQ showed insufficient validity in some items
      including symptom relief. The aim of this study was to examine the validity of
      the revised ELQ. MATERIALS AND METHODS: Data from 100 consecutive patients'
      medical records at two specialised palliative care units were used to complete
      new ELQs, which were then compared to the ELQ registrations from the SRPC for the
      same patients. The level of agreement was calculated for each ELQ item. To
      account for the possibility of the agreement occurring by chance, Cohen's kappa
      was calculated for suitable items. To examine the extent of registration mistakes
      when transferring the paper form to the web, the original paper versions of the
      ELQ filled out at the units were compared to data from the ELQs reported to the
      SRPC. RESULTS: Level of agreement between ELQ registrations from the SRPC and the
      new ELQs based on the medical records varied between 0.55 and 1.00, where 24
      items showed level of agreement above 0.80 and 9 items showed level of agreement
      below 0.80. Cohen's kappa with 95% confidence intervals was calculated for 24
      items. The kappa values showed that two items had poor agreement, four fair
      agreement, 11 moderate agreement, five good agreement and two very good
      agreement. The level of agreement varied between 0.93 and 1.00 when comparing the
      ELQ registrations in the SRPC and the paper forms. CONCLUSION: The revised ELQ
      contains more items with high levels of agreement between registrations in the
      SRPC and notes in the patients' medical records when compared to the previous
      version. Validating issues around symptom assessment remains a challenge in our
      model of quality assessment.

PMID- 29049397
TI  - The transcriptional regulator LysG (Rv1985c) of Mycobacterium tuberculosis
      activates lysE (Rv1986) in a lysine-dependent manner.
AB  - The Mycobacterium tuberculosis protein encoded by the Rv1986 gene is a target for
      memory T cells in patients with tuberculosis, and shows strong similarities to a
      lysine exporter LysE of Corynebacterium glutamicum. During infection, the
      pathogen Mycobacterium tuberculosis adapts its metabolism to environmental
      changes. In this study, we found that the expression of Rv1986 is controlled by
      Rv1985c. Rv1985c is located directly upstream of Rv1986 with an overlapping
      promoter region between both genes. Semiquantitative reverse transcription PCR
      using an isogenic mutant of Mycobacterium tuberculosis lacking Rv1985c showed
      that in the presence of lysine, Rv1985c protein positively upregulated the
      expression of Rv1986. RNA sequencing revealed the transcription start points for
      both transcripts and overlapping promoters. An inverted repeat in the center of
      the intergenic region was identified, and binding of Rv1985c protein to the
      intergenic region was confirmed by electrophoretic mobility shift assays. Whole
      transcriptome expression analysis and RNAsequencing showed downregulated
      transcription of ppsBCD in the Rv1985c-mutant compared to the wild type strain.
      Taken together, our findings characterize the regulatory network of Rv1985c in
      Mycobacterium tuberculosis. Due to their similarity of an orthologous gene pair
      in Corynebacterium glutamicum, we suggest to rename Rv1985c to lysG(Mt), and
      Rv1986 to lysE(Mt).

PMID- 29049398
TI  - Gravidity is not associated with telomere length in a biracial cohort of middle
      aged women: The Coronary Artery Risk Development in Young Adults (CARDIA) study.
AB  - OBJECTIVE: Having experienced 2-3 births is associated with reduced mortality
      versus women with <2 or >=4 births. The effect of 2-3 births on lifespan may be
      associated with delayed cellular aging. We hypothesized telomere length, a marker
      of cellular aging, would be longer in women who had 2-3 pregnancies. METHODS:
      Leukocyte telomere length was measured using quantitative real-time polymerase
      chain reaction in 620 women in CARDIA at the year 15 and 20 exams, expressed as
      the ratio of telomere repeat copy number to single-copy gene copy number (T/S).
      Number of pregnancies at the time of telomere length measurement was obtained
      (mean age = 41+/-0.1 years, average gravidity = 2.64+/-0.1 pregnancies).
      Participants were divided into 4 groups by number of pregnancies: 0, 1, 2-3, and
      >=4, to test for differences in telomere length by gravidity group. RESULTS: The
      mean and SD for telomere length was 0.98 +/- 0.20 T/S in the whole cohort. There
      were no differences in mean telomere length between groups; 0.98+/-0.02 T/S in
      women with 0 pregnancies, 1.01+/-0.02 T/S in women with 1 pregnancy, 0.97+/-0.01
      T/S in women with 2-3 pregnancies, and 0.99+/-0.02 T/S in women with >=4
      pregnancies (p = 0.51). We defined high-risk (shorter) telomere length as <=25th
      percentile, and low-risk (longer) telomere length as >=75 percentile. There were
      no differences in the prevalence of high-risk or low-risk telomere length between
      gravidity groups. CONCLUSIONS: Gravidity was not associated with telomere length
      in early middle age; the protective association of 2-3 births may act through
      other mechanisms.

PMID- 29049399
TI  - Density-dependence interacts with extrinsic mortality in shaping life histories.
AB  - The role of extrinsic mortality in shaping life histories is poorly understood.
      However, substantial evidence suggests that extrinsic mortality interacts with
      density-dependence in crucial ways. We develop a model combining Evolutionarily
      Stable Strategies with a projection matrix that allows resource allocation to
      growth, tissue repairs, and reproduction. Our model examines three cases, with
      density-dependence acting on: (i) mortality, (ii) fecundity, and (iii) production
      rate. We demonstrate that density-independent extrinsic mortality influences the
      rate of aging, age at maturity, growth rate, and adult size provided that density
      dependence acts on fertility or juvenile mortality. However, density-independent
      extrinsic mortality has no effect on these life history traits when density
      dependence acts on survival. We show that extrinsic mortality interacts with
      density-dependence via a compensation mechanism: the higher the extrinsic
      mortality the lower the strength of density-dependence. However, this
      compensation fully offsets the effect of extrinsic mortality only if density
      dependence acts on survival independently of age. Both the age-pattern and the
      type of density-dependence are crucial for shaping life history traits.

PMID- 29049400
TI  - Spoligotyping and whole-genome sequencing analysis of lineage 1 strains of
      Mycobacterium tuberculosis in Da Nang, Vietnam.
AB  - BACKGROUND: Spacer oligonucleotide typing (spoligotyping), a widely used,
      classical genotyping method for Mycobacterium tuberculosis complex (MTBC), is a
      PCR-based dot-blot hybridization technique to detect the genetic diversity of the
      direct repeat (DR) region. Of the seven major MTBC lineages in the world, lineage
      1 (Indo-Oceanic) mostly corresponds to the East African-Indian (EAI) spoligotype
      family in East Africa and Southeast Asia. OBJECTIVES: We investigated the genomic
      features of Vietnamese lineage 1 strains, comparing spoligotype patterns using
      whole-genome sequencing (WGS) data. METHODS: M. tuberculosis strains isolated in
      Da Nang, Vietnam were subjected to conventional spoligotyping, followed by WGS
      analysis using a high-throughput sequencer. Vietnamese lineage 1 strains were
      further analyzed with other lineage 1 strains obtained from a public database.
      RESULTS: Indicating a major spoligotype in Da Nang, 86 (46.2%) of the 186
      isolates belonged to the EAI family or lineage 1. Although typical EAI4-VNM
      strains are characterized by the deletion of spacers 26 and 27, 65 (75.6%) showed
      ambiguous signals on spacer 26. De novo assembly of the entire DR region and in
      silico spoligotyping analysis suggested the absence of spacer 26, and direct
      sequencing revealed that the 17th spacer sequence not used for conventional
      typing, was cross-hybridized to the spacer 26 probe. Vietnamese EAI4-VNM, other
      EAI-like strains, and those showing a non-EAI pattern lacking many spacers formed
      a monophyletic group separate from other EAI families in the world. CONCLUSION:
      Information about the alignment of spacers in the entire DR region obtained from
      WGS data provides a clue for the determination of experimentally ambiguous
      spoligo patterns. WGS data also helped to analyze the hidden relationships
      between apparently distinct spoligo patterns.

PMID- 29049402
TI  - Upward trends of acquired drug resistances in Ethiopian HIV-1C isolates: A decade
      longitudinal study.
AB  - BACKGROUND: The emergence, accumulation and spread of HIV-1 drug resistance
      strains in Africa could compromise the effectiveness of HIV treatment programs.
      This study was aimed at determining the incidence of virological failure and
      acquired drug resistance mutations overtime and identifying the most common
      mutational pathways of resistance in a well characterized HIV-1C infected
      Ethiopian cohort. METHODS: A total of 320 patients (220 ART naive and 100 on
      first lines ART) were included and followed. ART initiation and patients'
      monitoring was based on the WHO clinical and immunological parameters. HIV viral
      load measurement and genotypic drug resistance testing were done at baseline (T0
      2008) and after on average at a median time of 30 months on ART at three time
      points (T1-2011, T2-2013, T3-2015). FINDINGS: The incidence of virological
      failure has increased overtime from 11 at T1 to 17 at T2 and then to 30% at T3.
      At all time point's almost all of the patients with virological failure and
      accumulated drug resistance mutations had not met the WHO clinical and
      immunologic failure criteria and continued the failing regimen. A steep increase
      in the incidence and accumulation of major acquired NRTI and NNRTI drug
      resistance mutations have been observed (from 40% at T1 to 64% at T2 and then to
      66% at T3). The most frequent NRTIs drug resistance associated mutations are
      mainly the lamivudine-induced mutation M184V which was detected in 4 patients at
      T1 and showed a 2 fold increase in the following time points (T2: n = 8) and at
      (T3: n = 12) and the thymidine analogue mutations (such as D67N, K70R and K219E)
      which were not-detected at baseline T0 and T1 but were increased progressively to
      10 at T2 and to 17 at T3. The most frequent NNRTIs associated mutations were
      K103N, V106M and Y188C. CONCLUSIONS: An upward trend in the incidence of
      virological failure and accumulation of NRTI and NNRTI associated acquired
      antiretroviral drug resistance mutations are observed. The data suggest the need
      for virological monitoring, resistance testing for early detection of failure and
      access for TDF and PI containing drugs. Population-level and patient targeted
      interventions to prevent the spread of mutant variants is warranted.

PMID- 29049401
TI  - Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United
      States: A population-based study in SEER-Medicare.
AB  - OBJECTIVES: Intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinomas are
      rare tumors that arise from the epithelial cells of the bile ducts, and the
      etiology of both cancer types is poorly understood. Thus, we utilized the
      Surveillance, Epidemiology, and End Results (SEER)-Medicare resource to examine
      risk factors and novel preexisting medical conditions that may be associated with
      these cancer types. METHODS: Between 2000 and 2011, 2,092 ICC and 2,981 ECC cases
      and 323,615 controls were identified using the SEER-Medicare database. Logistic
      regression was used to calculate adjusted odds ratios (OR) and 95% confidence
      intervals (CI). RESULTS: Non-alcoholic fatty liver disease was associated with
      approximately 3-fold increased risks of ICC (OR = 3.52, 95% CI: 2.87-4.32) and
      ECC (OR = 2.93, 95% CI: 2.42-3.55). Other metabolic conditions, including obesity
      and type 2 diabetes, were also associated with increased risks of both cancer
      types. Smoking was associated with a 46% and 77% increased ICC and ECC risk,
      respectively. Several autoimmune/inflammatory conditions, including type 1
      diabetes and gout, were associated with increased risks of ICC/ECC. As
      anticipated, viral hepatitis, alcohol-related disorders, and bile duct conditions
      were associated with both cancer types. However, thyrotoxicosis and
      hemochromatosis were associated with an increased risk of ICC but not ECC, but
      did not remain significantly associated after Bonferroni correction. CONCLUSIONS:
      In this study, risk factors for ICC and ECC were similar, with the exceptions of
      thyrotoxicosis and hemochromatosis. Notably, metabolic conditions were associated
      with both cancer types. As metabolic conditions are increasing in prevalence,
      these could be increasingly important risk factors for both types of
      cholangiocarcinoma.

PMID- 29049403
TI  - The Multifeature Gait Score: An accurate way to assess gait quality.
AB  - PURPOSE: This study introduces a novel way to accurately assess gait quality.
      This new method called Multifeature Gait Score (MGS) is based on the computation
      of multiple parameters characterizing six aspects of gait (temporal, amplitude,
      variability, regularity, symmetry and complexity) quantified with one inertial
      sensor. According to the aspects described, parameters were aggregated into
      partial scores to indicate the altered aspect in the case of abnormal patterns.
      In order to evaluate the overall gait quality, partial scores were averaged to a
      global score. METHODS: The MGS was computed for 3 groups namely: healthy adult
      (10 subjects), sedentary elderly (11 subjects) and active elderly (20 subjects).
      Data were gathered from an inertial sensor located at the lumbar region during
      two sessions of 12m walking. RESULTS: The results based on ANOVA and Tukey tests
      showed that the partial scores with the exception of those which describe the
      symmetry aspect were able to discriminate between groups (p<0.05). This
      significant difference was also confirmed by the global score which shows a
      significantly lower value for the sedentary elderly group (3.58 +/-1.15) compared
      to the healthy adults (5.19 +/-0.84) and active elderly (4.82 +/-1.26). In
      addition, the intersession repeatability of the elaborated global score was
      excellent (ICC = 0.93, % SEM = 10.81). CONCLUSION: The results obtained support
      the reliability and the relevance of the MGS as a novel method to characterize
      gait quality.

PMID- 29049404
TI  - Low-complexity microbiota in the duodenum of children with newly diagnosed
      ulcerative colitis.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is characterized by gut dysbiosis.
      To date, the large bowel microbiota has been in focus. However, the microbiota of
      the small intestine may also be of importance, as the small bowel is a site for
      the induction and control of mucosal immune responses, which can be modulated by
      constituents of the local microbiota. METHODS: Duodenal fluids were collected
      during diagnostic work-up of treatment-naive children who were suspected of
      having IBD. The duodenal fluids were analyzed by pyrosequencing (average of
      32,000 reads/sample, read length of 500 nucleotides). After diagnosis, the
      duodenal microbiota of subjects with ulcerative colitis (N = 8) or Crohn's
      disease (N = 5), and non-IBD controls (N = 8) were compared. RESULTS:
      Pyrosequencing revealed that the duodenal microbiota of children with ulcerative
      colitis contained fewer Operational Taxonomic Units (OTUs) per individual than
      the duodenal microbiota of the controls (P = 0.005). This reduction in richness
      of the duodenal microbiota was seen for three major phyla: Firmicutes,
      Actinobacteria, and Bacteroidetes. Several bacterial genera were detected less
      frequently in the children with ulcerative colitis than in the non-IBD controls,
      including Collinsella (P = 0.001), Lactobacillus (P = 0.007), and Bacillus (P =
      0.007), as well as a non-identified member of the order Sphingobacteriales (P =
      0.007). CONCLUSIONS: In this pilot study, we show that the duodenal microbiota of
      children with ulcerative colitis exhibits reduced overall richness, despite the
      fact that the inflammation is primarily localized to the colon. These results
      should be corroborated in a larger study.

PMID- 29049405
TI  - Differences in pupillary light reflex between optic neuritis and ischemic optic
      neuropathy.
AB  - OBJECTIVES: To determine the differences in pupillary light reflex (PLR) between
      the acute and chronic phases of optic neuritis (ON) and nonarteritic anterior
      ischemic optic neuropathy (NAION). METHODS: The study included 30 patients with
      ON and 22 patients with NAION whose PLR were measured by a dynamic pupillometer
      (PLR-200; NeurOptics Inc., Irvine, USA). Age-matched controls included 58 healthy
      individuals with normal vision and optic nerve function. Pupil diameters,
      latency, constriction ratio, constriction velocity and dilation velocity were
      noted. The differences in PLR measurements were compared among the acute and
      chronic phases of ON and NAION, and in age-matched controls. Regression analysis
      determined factors associated with PLR measurements, including visual acuity,
      color vision defect, visual field defects and retinal nerve fiber layer thickness
      measurements on optical coherence tomography. RESULTS: Pupillary constriction
      velocity, constriction ratio and latency were all significantly decreased in the
      acute phase of ON and NAION. ON showed significantly delayed constriction latency
      compared to NAION (P = 0.047). Pupillary constriction velocity, constriction
      ratio and latency were recovered in the chronic phase of ON (P = 0.038, 0.018,
      and 0.045), however, these parameters were not recovered in NAION (P = 0.693,
      0.173 and 0.994). CONCLUSIONS: Pupillary constriction velocity, constriction
      ratio, and latency were significantly decreased in the acute phase of ON and
      NAION compared to normal controls. ON showed delayed constriction latency
      compared to NAION. Decreased PLR were recovered in the chronic phase of ON, but
      not in NAION.

PMID- 29049407
TI  - Correction: The lithic assemblages of Donggutuo, Nihewan basin: Knapping skills
      of Early Pleistocene hominins in North China.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185101.].

PMID- 29049408
TI  - Long-term trends of phosphorus concentrations in an artificial lake: Socio
      economic and climate drivers.
AB  - European freshwater ecosystems have undergone significant human-induced and
      environmentally-driven variations in nutrient export from catchments throughout
      the past five decades, mainly in connection with changes in land-use,
      agricultural practice, waste water production and treatment, and climatic
      conditions. We analysed the relations among concentration of total phosphorus
      (TP) in the Slapy Reservoir (a middle reservoir of the Vltava River Cascade,
      Czechia), and socio-economic and climatic factors from 1963 to 2015. The study
      was based on a time series analysis, using conventional statistical tools, and
      the identification of breaking points, using a segmented regression. Results
      indicated clear long-term trends and seasonal patterns of TP, with annual average
      TP increasing up until 1991 and decreasing from 1992 to 2015. Trends in annual,
      winter and spring average TP concentrations reflected a shift in development of
      sewerage and sanitary infrastructure, agricultural application of fertilizers,
      and livestock production in the early 1990s that was associated with changes from
      the planned to the market economy. No trends were observed for average TP in
      autumn. The summer average TP has fluctuated with increased amplitude since 1991
      in connection with recent climate warming, changes in thermal stratification
      stability, increased water flow irregularities, and short-circuiting of TP-rich
      inflow during high flow events. The climate-change-induced processes confound the
      generally declining trend in lake-water TP concentration and can result in
      eutrophication despite decreased phosphorus loads from the catchment. Our
      findings indicate the need of further reduction of phosphorus sources to meet
      ecological quality standards of the EU Water Framework Directive because the
      climate change may lead to a greater susceptibility of the aquatic ecosystem to
      the supply of nutrients.

PMID- 29049406
TI  - Distinct prediction errors in mesostriatal circuits of the human brain mediate
      learning about the values of both states and actions: evidence from high
      resolution fMRI.
AB  - Prediction-error signals consistent with formal models of "reinforcement
      learning" (RL) have repeatedly been found within dopaminergic nuclei of the
      midbrain and dopaminoceptive areas of the striatum. However, the precise form of
      the RL algorithms implemented in the human brain is not yet well determined.
      Here, we created a novel paradigm optimized to dissociate the subtypes of reward
      prediction errors that function as the key computational signatures of two
      distinct classes of RL models-namely, "actor/critic" models and action-value
      learning models (e.g., the Q-learning model). The state-value-prediction error
      (SVPE), which is independent of actions, is a hallmark of the actor/critic
      architecture, whereas the action-value-prediction error (AVPE) is the
      distinguishing feature of action-value-learning algorithms. To test for the
      presence of these prediction-error signals in the brain, we scanned human
      participants with a high-resolution functional magnetic-resonance imaging (fMRI)
      protocol optimized to enable measurement of neural activity in the dopaminergic
      midbrain as well as the striatal areas to which it projects. In keeping with the
      actor/critic model, the SVPE signal was detected in the substantia nigra. The
      SVPE was also clearly present in both the ventral striatum and the dorsal
      striatum. However, alongside these purely state-value-based computations we also
      found evidence for AVPE signals throughout the striatum. These high-resolution
      fMRI findings suggest that model-free aspects of reward learning in humans can be
      explained algorithmically with RL in terms of an actor/critic mechanism operating
      in parallel with a system for more direct action-value learning.

PMID- 29049409
TI  - Protocol vulnerability detection based on network traffic analysis and binary
      reverse engineering.
AB  - Network protocol vulnerability detection plays an important role in many domains,
      including protocol security analysis, application security, and network intrusion
      detection. In this study, by analyzing the general fuzzing method of network
      protocols, we propose a novel approach that combines network traffic analysis
      with the binary reverse engineering method. For network traffic analysis, the
      block-based protocol description language is introduced to construct test
      scripts, while the binary reverse engineering method employs the genetic
      algorithm with a fitness function designed to focus on code coverage. This
      combination leads to a substantial improvement in fuzz testing for network
      protocols. We build a prototype system and use it to test several real-world
      network protocol implementations. The experimental results show that the proposed
      approach detects vulnerabilities more efficiently and effectively than general
      fuzzing methods such as SPIKE.

PMID- 29049410
TI  - Metamorphopsia associated with central retinal vein occlusion.
AB  - This prospective study aimed to investigate metamorphopsia in eyes with central
      retinal vein occlusion (CRVO) and included 28 eyes (28 patients) with unilateral
      CRVO that had macular edema (ME) in the acute phase. The ME was treated with anti
      vascular endothelial growth factor agents. At baseline and at 1 and 6 months
      after initiation of treatment, quantitative measurements of metamorphopsia were
      performed using M-CHARTS and the retinal morphologic changes were examined by
      optical coherence tomography. At baseline, metamorphopsia was detected on M
      CHARTS in 14 (50.0%) eyes. The mean M-CHARTS score was 0.37 +/- 0.53. At 1 month
      and 6 months after initiation of treatment, there was substantial resolution of
      ME and significant recovery of visual acuity. In contrast, metamorphopsia was
      still detected in 16 eyes at 6 months; the mean M-CHARTS scores were 0.29 +/-
      0.37 at 1 month and 0.32 +/- 0.38 at 6 months, and had not significantly improved
      from baseline (p = 0.580, and p = 0.604, respectively). Although the M-CHARTS
      score at 6 months was associated with the baseline M-CHARTS score (p = 0.004), it
      did not have any associations with morphologic parameters at baseline. However,
      the M-CHARTS score at 6 months was significantly associated with foveal
      photoreceptor status, height of serous detachment, and parafoveal thickening at 1
      month. Metamorphopsia associated with CRVO could be quantified using M-CHARTS,
      and often persisted in contrast with the recovery of visual acuity and resolution
      of ME after treatment with anti-vascular endothelial growth factor agents.

PMID- 29049411
TI  - XRCC5 cooperates with p300 to promote cyclooxygenase-2 expression and tumor
      growth in colon cancers.
AB  - Cyclooxygenase (COX) is the rate-limiting enzyme in prostaglandins (PGs)
      biosynthesis. Previous studies indicate that COX-2, one of the isoforms of COX,
      is highly expressed in colon cancers and plays a key role in colon cancer
      carcinogenesis. Thus, searching for novel transcription factors regulating COX-2
      expression will facilitate drug development for colon cancer. In this study, we
      identified XRCC5 as a binding protein of the COX-2 gene promoter in colon cancer
      cells with streptavidin-agarose pulldown assay and mass spectrometry analysis,
      and found that XRCC5 promoted colon cancer growth through modulation of COX-2
      signaling. Knockdown of XRCC5 by siRNAs inhibited the growth of colon cancer
      cells in vitro and of tumor xenografts in a mouse model in vivo by suppressing
      COX-2 promoter activity and COX-2 protein expression. Conversely, overexpression
      of XRCC5 promoted the growth of colon cancer cells by activating COX-2 promoter
      and increasing COX-2 protein expression. Moreover, the role of p300 (a
      transcription co-activator) in acetylating XRCC5 to co-regulate COX-2 expression
      was also evaluated. Immunofluorescence assay and confocal microscopy showed that
      XRCC5 and p300 proteins were co-located in the nucleus of colon cancer cells. Co
      immunoprecipitation assay also proved the interaction between XRCC5 and p300 in
      nuclear proteins of colon cancer cells. Cell viability assay indicated that the
      overexpression of wild-type p300, but not its histone acetyltransferase (HAT)
      domain deletion mutant, increased XRCC5 acetylation, thereby up-regulated COX-2
      expression and promoted the growth of colon cancer cells. In contrast,
      suppression of p300 by a p300 HAT-specific inhibitor (C646) inhibited colon
      cancer cell growth by suppressing COX-2 expression. Taken together, our results
      demonstrated that XRCC5 promoted colon cancer growth by cooperating with p300 to
      regulate COX-2 expression, and suggested that the XRCC5/p300/COX-2 signaling
      pathway was a potential target in the treatment of colon cancers.

PMID- 29049412
TI  - Measuring facility capability to provide routine and emergency childbirth care to
      mothers and newborns: An appeal to adjust for delivery caseload of facilities.
AB  - BACKGROUND: Measurement of Emergency Obstetric Care capability is common, and
      measurement of newborn and overall routine childbirth care has begun in recent
      years. These assessments of facility capabilities can be used to identify
      geographic inequalities in access to functional health services and to monitor
      improvements over time. This paper develops an approach for monitoring the
      childbirth environment that accounts for the delivery caseload of the facility.
      METHODS: We used data from the Kenya Service Provision Assessment to examine
      facility capability to provide quality childbirth care, including infrastructure,
      routine maternal and newborn care, and emergency obstetric and newborn care. A
      facility was considered capable of providing a function if necessary tracer items
      were present and, for emergency functions, if the function had been performed in
      the previous three months. We weighted facility capability by delivery caseload,
      and compared results with those generated using traditional "survey weights".
      RESULTS: Of the 403 facilities providing childbirth care, the proportion meeting
      criteria for capability were: 13% for general infrastructure, 6% for basic
      emergency obstetric care, 3% for basic emergency newborn care, 13% and 11% for
      routine maternal and newborn care, respectively. When the new caseload weights
      accounting for delivery volume were applied, capability improved and the
      proportions of deliveries occurring in a facility meeting capability criteria
      were: 51% for general infrastructure, 46% for basic emergency obstetric care, 12%
      for basic emergency newborn care, 36% and 18% for routine maternal and newborn
      care, respectively. This is because most of the caseload was in hospitals, which
      generally had better capability. Despite these findings, fewer than 2% of
      deliveries occurred in a facility capable of providing all functions. CONCLUSION:
      Reporting on the percentage of facilities capable of providing certain functions
      misrepresents the capacity to provide care at the national level. Delivery
      caseload weights allow adjustment for patient volume, and shift the denominator
      of measurement from facilities to individual deliveries, leading to a better
      representation of the context in which facility births take place. These methods
      could lead to more standardized national datasets, enhancing their ability to
      inform policy at a national and international level.

PMID- 29049413
TI  - MicroRNA expression analysis of feline and canine parvovirus infection in vivo
      (felis).
AB  - Feline panleukopenia is a common contagious disease with high morbidity and
      mortality. At present, feline parvovirus (FPV) and canine parvovirus (CPV)
      variants are the pathogens of feline panleukopenia. Many studies have shown that
      miRNAs are involved in virus-host interactions. Nevertheless, miRNA expression
      profiling of FPV (original virus) or CPV-2b (new virus) in cats has not been
      reported. To investigate these profiles, three 10-week-old cats were orally
      inoculated with 106 TCID50 of the viruses (FPV and CPV-2b), and the jejunums of
      one cat in each group were sectioned for miRNA sequencing at 5 days post
      inoculation (dpi). This study is the first attempt to use miRNA analysis to
      understand the molecular basis of FPV and CPV infection in cats. The miRNA
      expression profiles of the jejunums of cats infected with FPV and CPV were
      obtained, and a subset of miRNAs was validated by real-time qPCR. The results
      show that a variety of metabolism-related pathways, cytokine- and pathogen-host
      interaction-related pathways, and pathology- and cellar structure-related
      pathways, as well as others, were affected. Specifically, the JAK-STAT signaling
      pathway, which is critical for cytokines and growth factors, was enriched. This
      description of the miRNAs involved in regulating FPV and CPV infection in vivo
      provides further insight into the mechanisms of viral infection and adaptation
      and might provide an alternative antiviral strategy for disease control and
      prevention.

PMID- 29049414
TI  - Wavelet Imaging on Multiple Scales (WIMS) reveals focal adhesion distributions,
      dynamics and coupling between actomyosin bundle stability.
AB  - We introduce and use Wavelet Imaging on Multiple Scales (WIMS) as an improvement
      to fluorescence correlation spectroscopy to measure physical processes and
      features that occur across multiple length scales. In this study, wavelet
      transforms of cell images are used to characterize molecular dynamics at the
      cellular and subcellular levels (i.e. focal adhesions). We show the usefulness of
      the technique by applying WIMS to an image time series of a migrating
      osteosarcoma cell expressing fluorescently labelled adhesion proteins, which
      allows us to characterize different components of the cell ranging from optical
      resolution scale through to focal adhesion and whole cell size scales. Using WIMS
      we measured focal adhesion numbers, orientation and cell boundary velocities for
      retraction and protrusion. We also determine the internal dynamics of individual
      focal adhesions undergoing assembly, disassembly or elongation. Thus confirming
      as previously shown, WIMS reveals that the number of adhesions and the area of
      the protruding region of the cell are strongly correlated, establishing a
      correlation between protrusion size and adhesion dynamics. We also apply this
      technique to characterize the behavior of adhesions, actin and myosin in Chinese
      hamster ovary cells expressing a mutant form of myosin IIB (1935D) that displays
      decreased filament stability and impairs front-back cell polarity. We find
      separate populations of actin and myosin at each adhesion pole for both the
      mutant and wild type form. However, we find these populations move rapidly
      inwards toward one another in the mutant case in contrast to the cells that
      express wild type myosin IIB where those populations remain stationary. Results
      obtained with these two systems demonstrate how WIMS has the potential to reveal
      novel correlations between chosen parameters that belong to different scales.

PMID- 29049415
TI  - Effect of diacerein on renal function and inflammatory cytokines in participants
      with type 2 diabetes mellitus and chronic kidney disease: A randomized controlled
      trial.
AB  - : Diacerein seems to improve metabolic control and reduce inflammatory marker
      levels in individuals with type 2 diabetes mellitus (Type 2 DM), but for
      participants with chronic kidney disease (CKD) its effect is unknown. This study
      aimed to evaluate the effect of diacerein vs. placebo on urinary
      albumin/creatinine ratio (ACR), glomerular filtration rate (GFR), and
      inflammatory cytokines in type 2 DM participants with CKD. Blood pressure (BP)
      and metabolic control were secondary outcomes. This randomized, placebo
      controlled, parallel trial of adjuvant treatment of type 2 DM with diacerein
      enrolled seventy-two participants with CKD, aged 30-80 years, with glycated
      hemoglobin levels from 53-97 mmol/mol (7.0-11.0%), receiving angiotensin
      converting enzyme inhibitors or angiotensin receptor blockers and antidiabetic
      agents. Participants randomized to diacerein or placebo were followed-up up to 90
      days. Both groups had a marked reduction in ACR, but there was no effect on
      glomerular filtration rate. While the diacerein group had reduced TNF-alpha
      levels at the 75th percentile with a borderline significance (P = 0.05), there
      were no changes in the IL levels at the 75th percentile. Diacerein prevented the
      increase in blood glucose to the level observed in the placebo group (P = 0.04),
      improving metabolic control by 74%, reducing 24-hour diastolic BP, nighttime
      systolic and diastolic BP compared to the placebo group. In conclusion, among
      patients with type 2 DM and CKD, diacerein does not have an effect on ACR or GFR,
      but slows metabolic control deterioration and is associated with lower nighttime
      systolic and diastolic blood pressure. TRIAL REGISTRATION: Brazilian Clinical
      Trials Registry (Registro Brasileiro de Ensaios Clinicos; ReBeC) U1111-1156-0255.

PMID- 29049416
TI  - Musicians have better memory than nonmusicians: A meta-analysis.
AB  - BACKGROUND: Several studies have found that musicians perform better than
      nonmusicians in memory tasks, but this is not always the case, and the strength
      of this apparent advantage is unknown. Here, we conducted a meta-analysis with
      the aim of clarifying whether musicians perform better than nonmusicians in
      memory tasks. METHODS: Education Source; PEP (WEB)-Psychoanalytic Electronic
      Publishing; Psychology and Behavioral Science (EBSCO); PsycINFO (Ovid); PubMed;
      ScienceDirect-AllBooks Content (Elsevier API); SCOPUS (Elsevier API); SocINDEX
      with Full Text (EBSCO) and Google Scholar were searched for eligible studies. The
      selected studies involved two groups of participants: young adult musicians and
      nonmusicians. All the studies included memory tasks (loading long-term, short
      term or working memory) that contained tonal, verbal or visuospatial stimuli.
      Three meta-analyses were run separately for long-term memory, short-term memory
      and working memory. RESULTS: We collected 29 studies, including 53 memory tasks.
      The results showed that musicians performed better than nonmusicians in terms of
      long-term memory, g = .29, 95% CI (.08-.51), short-term memory, g = .57, 95% CI
      (.41-.73), and working memory, g = .56, 95% CI (.33-.80). To further explore the
      data, we included a moderator (the type of stimulus presented, i.e., tonal,
      verbal or visuospatial), which was found to influence the effect size for short
      term and working memory, but not for long-term memory. In terms of short-term and
      working memory, the musicians' advantage was large with tonal stimuli, moderate
      with verbal stimuli, and small or null with visuospatial stimuli. CONCLUSIONS:
      The three meta-analyses revealed a small effect size for long-term memory, and a
      medium effect size for short-term and working memory, suggesting that musicians
      perform better than nonmusicians in memory tasks. Moreover, the effect of the
      moderator suggested that, the type of stimuli influences this advantage.

PMID- 29049417
TI  - Decrypting the Polyporus dictyopus complex: Recovery of Atroporus Ryvarden and
      segregation of Neodictyopus gen. nov. (Polyporales, Basidiomyocta).
AB  - Polyporus dictyopus, with a large number of heterotypic synonyms, has been
      traditionally considered a species complex, characterized by wide morphological
      variation and geographic distribution. Thus, neotropical specimens previously
      identified as P. dictyopus from Amazonia, Cerrado and Atlantic Forest biomes were
      studied based on detailed macro- and micromorphological examination and
      phylogenetic analyses, using distinct ribosomal and protein-coding genomic
      regions: the nuclear ribosomal internal transcribed spacer (nrITS), nuclear
      ribosomal large subunit (nrLSU), and RNA polymerase II second subunit (RPB2). Two
      unrelated generic lineages, each one represented by different species, are
      reported: Atroporus is recovered and re-circumscribed to include A. diabolicus
      and A. rufoatratus comb. nov.; Neodictyopus gen. nov. is proposed to accommodate
      N. dictyopus comb. nov. and two new species, N. atlanticae and N. gugliottae. Our
      study showed that at least five distinct species were hidden under the name P.
      dictyopus. Detailed descriptions, pictures, illustrations, and a key are provided
      for Atroporus and Neodictyopus species.

PMID- 29049418
TI  - Effects of femtosecond laser and other surface treatments on the bond strength of
      metallic and ceramic orthodontic brackets to zirconia.
AB  - Femtosecond laser has been proposed as a method for conditioning zirconia
      surfaces to boost bond strength. However, metallic or ceramic bracket bonding to
      femtosecond laser-treated zirconia surfaces has not been tested. This study
      compared the effects of four conditioning techniques, including femtosecond laser
      irradiation, on shear bond strength (SBS) of metallic and ceramic brackets to
      zirconia.Three hundred zirconia plates were divided into five groups: 1) control
      (C); 2) sandblasting (APA); 3) silica coating and silane (SC); 4) femtosecond
      laser (FS); 5) sandblasting followed by femtosecond laser (APA+SC). A thermal
      imaging camera measured temperature changes in the zirconia during irradiation.
      Each group was divided into 2 subgroups (metallic vs ceramic brackets). SBS was
      evaluated using a universal testing machine. The adhesive remnant index (ARI) was
      registered and surfaces were observed under SEM. Surface treatment and bracket
      type significantly affected the bracket-zirconia bond strength. SBS was
      significantly higher (p<0.001) for ceramic brackets in all groups (APA+FS > APA >
      FS > SC > control) than metallic brackets (APA+FS > FS > SC > APA > control). For
      metallic brackets, groups SC (5.99 +/- 1.86 MPa), FS (6.72 +/- 2.30 MPa) and
      APA+FS (7.22 +/- 2.73 MPa) reported significantly higher bond strengths than
      other groups (p < 0.05). For ceramic brackets, the highest bond strength values
      were obtained in groups APA (25.01 +/- 4.45 MPa), FS (23.18 +/- 6.51 MPa) and
      APA+FS (29.22 +/- 8.20 MPa).Femtosecond laser enhances bond strength of ceramic
      and metallic brackets to zirconia. Ceramic brackets provide significantly
      stronger adhesion than metallic brackets regardless of the surface treatment
      method.

PMID- 29049419
TI  - Multi-time series RNA-seq analysis of Enterobacter lignolyticus SCF1 during
      growth in lignin-amended medium.
AB  - The production of lignocellulosic-derived biofuels is a highly promising source
      of alternative energy, but it has been constrained by the lack of a microbial
      platform capable to efficiently degrade this recalcitrant material and cope with
      by-products that can be toxic to cells. Species that naturally grow in
      environments where carbon is mainly available as lignin are promising for finding
      new ways of removing the lignin that protects cellulose for improved conversion
      of lignin to fuel precursors. Enterobacter lignolyticus SCF1 is a facultative
      anaerobic Gammaproteobacteria isolated from tropical rain forest soil collected
      in El Yunque forest, Puerto Rico under anoxic growth conditions with lignin as
      sole carbon source. Whole transcriptome analysis of SCF1 during E.lignolyticus
      SCF1 lignin degradation was conducted on cells grown in the presence (0.1%, w/w)
      and the absence of lignin, where samples were taken at three different times
      during growth, beginning of exponential phase, mid-exponential phase and
      beginning of stationary phase. Lignin-amended cultures achieved twice the cell
      biomass as unamended cultures over three days, and in this time degraded 60% of
      lignin. Transcripts in early exponential phase reflected this accelerated growth.
      A complement of laccases, aryl-alcohol dehydrogenases, and peroxidases were most
      up-regulated in lignin amended conditions in mid-exponential and early stationary
      phases compared to unamended growth. The association of hydrogen production by
      way of the formate hydrogenlyase complex with lignin degradation suggests a
      possible value added to lignin degradation in the future.

PMID- 29049420
TI  - Production of proinflammatory mediators in activated microglia is synergistically
      regulated by Notch-1, glycogen synthase kinase (GSK-3beta) and NF-kappaB/p65
      signalling.
AB  - Microglia activation and associated inflammatory response are involved in the
      pathogenesis of different neurodegenerative diseases. We have reported that Notch
      1 and NF-kappaB/p65 signalling pathways operate in synergy in regulating the
      production of proinflammatory mediators in activated microglia. In the latter,
      there is also evidence by others that glycogen synthase kinase 3beta (GSK-3beta)
      mediates the release of proinflammatory cytokines but the interrelationships
      between the three signalling pathways have not been fully clarified. This is an
      important issue as activated microglia are potential therapeutic target for
      amelioration of microglia mediated neuroinflammation. Here we show that blocking
      of Notch-1 with N-[(3,5-Difluorophenyl) acetyl]-L-alanyl-2-phenylglycine-1,1
      dimethylethyl ester (DAPT) in LPS activated BV-2 microglia not only suppressed
      Notch intracellular domain (NICD) and Hes-1 protein expression, but also that of
      GSK-3beta. Conversely, blocking of the latter with lithium chloride (LiCl)
      decreased NICD expression in a dose-dependent manner; moreover, Hes-1
      immunofluorescence was attenuated. Along with this, the protein expression level
      of p-GSK-3beta and p-AKT protein expression was significantly increased.
      Furthermore, DAPT and LiCl decreased production of IL-1beta, TNF-alpha, IL-6,
      iNOS, Cox2 and MCP-1; however, IL-10 expression was increased notably in LiCl
      treated cells. The effects of DAPT and LiCl on changes of the above-mentioned
      biomarkers were confirmed by immunofluorescence in both BV-2 and primary
      microglia. Additionally, NF-kappaB/p65 immunofluorescence was attenuated by DAPT
      and LiCl; as opposed to this, IkappaBalpha protein expression was increased.
      Taken together, it is suggested that Notch-1, NF-kappaB/p65 and GSK-3beta operate
      in synergy to inhibit microglia activation. This may be effected via increased
      expression of phospho-GSK-3beta (p-GSK-3beta), phospho-protein kinase B (PKB) (p
      AKT) and IkappaBalpha. It is concluded that the three signalling pathways are
      functionally interlinked in regulating microglia activation.

PMID- 29049421
TI  - Complementary religious and spiritual interventions in physical health and
      quality of life: A systematic review of randomized controlled clinical trials.
AB  - OBJECTIVE: To examine whether religious and spiritual interventions (RSIs) can
      promote physical health and quality of life in individuals. METHODS: The
      following databases were used to conduct a systematic review: PubMed, Scopus, Web
      of Science, EMBASE, PsycINFO, Cochrane, and Scielo. Randomized controlled trials
      that evaluated RSIs regarding physical health outcomes and/or quality of life in
      English, Spanish or Portuguese were included. RSI protocols performed at a
      distance (i.e. intercessory prayer) or for psychiatric disorders were excluded.
      This study consisted of two phases: (a) reading titles and abstracts, and (b)
      assessing the full articles and their methodological quality using the Cochrane
      Back Review Group scale. RESULTS: In total, 7,070 articles were identified in the
      search, but 6884 were excluded in phase 1 because they were off topic or repeated
      in databases. Among the 186 articles included in phase 2, 140 were excluded
      because they did not fit the inclusion criteria and 16 did not have adequate
      randomization process. Thus, a final selection of 30 articles remained. The
      participants of the selected studies were classified in three groups: chronic
      patients (e.g., cancer, obesity, pain), healthy individuals and healthcare
      professionals. The outcomes assessed included quality of life, physical activity,
      pain, cardiac outcomes, promotion of health behaviors, clinical practice of
      healthcare professionals and satisfaction with protocols. The divergence
      concerning scales and protocols proposed did not allow a meta-analysis. RSIs as a
      psychotherapy approach were performed in 40% of the studies, and the control
      group was more likely to use an educational intervention (56.7%). The results
      revealed small effect sizes favoring RSIs in quality of life and pain outcomes
      and very small effects sizes in physical activity, promotion of health behaviors
      and clinical practice of health professionals compared with other complementary
      strategies. Other outcomes, such as cardiac measures and satisfaction with the
      protocols, revealed no evidence for RSIs. Regarding the quality of the selected
      articles according to the Cochrane Back Review Group Scale, the average score was
      6.83 (SD = 9.08) on a scale of 11, demonstrating robustness in the studies.
      CONCLUSION: Clinical trials on RSIs demonstrated that they had small benefits
      compared with other complementary health therapies by reducing pain and weight,
      improving quality of life and promoting health behaviors. The lack of clinical
      trials that included biological outcomes and the diversity of approaches indicate
      a need for more studies to understand the possible mechanisms of action of RSIs
      and their roles in health care.

PMID- 29049423
TI  - Dynamic water patterns change the stability of the collapsed filter conformation
      of the KcsA K+ channel.
AB  - The selectivity filter of the KcsA K+ channel has two typical conformations-the
      conductive and the collapsed conformations, respectively. The transition from the
      conductive to the collapsed filter conformation can represent the process of
      inactivation that depends on many environmental factors. Water molecules
      permeating behind the filter can influence the collapsed filter stability. Here
      we perform the molecular dynamics simulations to study the stability of the
      collapsed filter of the KcsA K+ channel under the different water patterns. We
      find that the water patterns are dynamic behind the collapsed filter and the
      filter stability increases with the increasing number of water molecules. In
      addition, the stability increases significantly when water molecules distribute
      uniformly behind the four monomeric filter chains, and the stability is
      compromised if water molecules only cluster behind one or two adjacent filter
      chains. The altered filter stabilities thus suggest that the collapsed filter can
      inactivate gradually under the dynamic water patterns. We also demonstrate how
      the different water patterns affect the filter recovery from the collapsed
      conformation.

PMID- 29049422
TI  - Thoracic trauma now and then: A 10 year experience from 16,773 severely injured
      patients.
AB  - BACKGROUND AND PURPOSE: Thoracic trauma remains to be a relevant injury to the
      polytraumatised patient. However, literature regarding how far changes in
      clinical guidelines for pre- and in-hospital trauma management and diagnostic
      procedures affect the outcome of multiple injured patients with severe chest
      injury during a long-term observation period is sparse. METHODS: Multiple
      traumatised patients (age>=16y) documented in the TraumaRegister DGU(r) (TR-DGU)
      from January 1st 2005 to December 31st 2014 with severe chest trauma (AIS>=3)
      were included in this study. Demographic data, the pattern of injury, injury
      severity, radiographic emergency procedures, indication for intubation, duration
      of mechanical ventilation, emergency surgery, occurrence of complications and
      mortality were evaluated per year and over time. RESULTS: A total of 16,773
      patients were analysed. The use of whole body computer tomography increased
      (p<0.001), while the incidence of plain x-rays decreased (p<0.001). Furthermore,
      incidence of AISThorax = 3 graded injuries increased (p<0.001) while AISThorax =
      4 decreased (p<0.001). Both, rate of patients being intubated at the time of ICU
      admission decreased (p<0.001) and the time of mechanical ventilation decreased
      (p<0.001). Additionally, need for emergency surgery, lung failure, sepsis, and
      multi organ failure all decreased (p<0.001). However, mortality remained
      unchanged. INTERPRETATION: Severity of severe chest trauma and associated
      complications decreased while diagnostics and treatment improved over time.
      However, mortality remained unchanged. Our results are in line with those
      expected in the context of the incidence of CT diagnostics, which has increased
      parallel to the clinical outcome Thus, our data demonstrate a positive trend in
      the treatment of patients with severe chest trauma.

PMID- 29049425
TI  - Comparison of Internal Medicine and General Surgery Residents' Assessments of
      Risk of Postsurgical Complications in Surgically Complex Patients.

PMID- 29049426
TI  - Are Surgical Residents Prepared to Care for Transgender Patients?

PMID- 29049424
TI  - Diagnostic Accuracy of Virtual Pathology vs Traditional Microscopy in a Large
      Dermatopathology Study.
AB  - Importance: Digital pathology represents a transformative technology that impacts
      dermatologists and dermatopathologists from residency to academic and private
      practice. Two concerns are accuracy of interpretation from whole-slide images
      (WSI) and effect on workflow. Studies of considerably large series involving
      single-organ systems are lacking. Objective: To evaluate whether diagnosis from
      WSI on a digital microscope is inferior to diagnosis of glass slides from
      traditional microscopy (TM) in a large cohort of dermatopathology cases with
      attention on image resolution, specifically eosinophils in inflammatory cases and
      mitotic figures in melanomas, and to measure the workflow efficiency of WSI
      compared with TM. Design, Setting, and Participants: Three dermatopathologists
      established interobserver ground truth consensus (GTC) diagnosis for 499
      previously diagnosed cases proportionally representing the spectrum of diagnoses
      seen in the laboratory. Cases were distributed to 3 different dermatopathologists
      who diagnosed by WSI and TM with a minimum 30-day washout between methodologies.
      Intraobserver WSI/TM diagnoses were compared, followed by interobserver
      comparison with GTC. Concordance, major discrepancies, and minor discrepancies
      were calculated and analyzed by paired noninferiority testing. We also measured
      pathologists' read rates to evaluate workflow efficiency between WSI and TM. This
      retrospective study was caried out in an independent, national, university
      affiliated dermatopathology laboratory. Main Outcomes and Measures: Intraobserver
      concordance of diagnoses between WSI and TM methods and interobserver variance
      from GTC, following College of American Pathology guidelines. Results: Mean
      intraobserver concordance between WSI and TM was 94%. Mean interobserver
      concordance was 94% for WSI and GTC and 94% for TM and GTC. Mean interobserver
      concordance between WSI, TM, and GTC was 91%. Diagnoses from WSI were noninferior
      to those from TM. Whole-slide image read rates were commensurate with WSI
      experience, achieving parity with TM by the most experienced user. Conclusions
      and Relevance: Diagnosis from WSI was found equivalent to diagnosis from glass
      slides using TM in this statistically powerful study of 499 dermatopathology
      cases. This study supports the viability of WSI for primary diagnosis in the
      clinical setting.

PMID- 29049427
TI  - How Much Time Should We Be Spending With Electronic Health Records?

PMID- 29049428
TI  - Risk, Complexity, Decision Making, and Patient Care.

PMID- 29049430
TI  - Abnormal Magnetic Resonance Imaging Findings in a Patient With Optic Disc Edema,
      Retinal Hemorrhage, and Decreased Vision.

PMID- 29049431
TI  - Dopamine Dysfunction in Schizophrenia and Bipolar Disorder-Never the Twain Shall
      Meet?

PMID- 29049429
TI  - Correlation of Handheld Reflectance Confocal Microscopy With Radial Video
      Mosaicing for Margin Mapping of Lentigo Maligna and Lentigo Maligna Melanoma.
AB  - Importance: The management of lentigo maligna (LM) and LM melanoma (LMM) is
      challenging because of extensive subclinical spread and its occurrence on
      cosmetically sensitive areas. Reflectance confocal microscopy (RCM) improves
      diagnostic accuracy for LM and LMM and can be used to delineate their margins.
      Objectives: To evaluate whether handheld RCM with radial video mosaicing (HRCM
      RV) offers accurate presurgical assessment of LM and LMM margins. Design,
      Setting, and Participants: This prospective study included consecutive patients
      with biopsy-proven LM and LMM located on the head and neck area who sought
      consultation for surgical management from March 1, 2016, through March 31, 2017,
      at the Dermatology Service of the Memorial Sloan Kettering Cancer Center. Thirty
      two patients underwent imaging using HRCM-RV, and 22 patients with 23 LM or LMM
      lesions underwent staged surgery and contributed to the analysis. Main Outcomes
      and Measures: Clinical lesion size and area, LM and LMM area based on HRCM-RV
      findings, surgical defect area estimated by HRCM-RV, and observed surgical defect
      area. In addition, the margins measured in millimeters estimated for tumor
      clearance in each quadrant based on HRCM-RV findings were calculated and compared
      with the surgical margins. Results: Among the 22 patients (12 men and 10 women;
      mean [SD] age, 69.0 [8.6] years [range, 46-83 years]) with 23 lesions included in
      the final analysis, the mean (SD) surgical defect area estimated with HRCM-RV was
      6.34 (4.02) cm2 and the mean (SD) area of surgical excision with clear margins
      was 7.74 (5.28) cm2. Overall, controlling for patient age and previous surgery,
      surgical margins were a mean of 0.76 mm (95% CI, 0.67-0.84 mm; P < .001) larger
      than the HRCM-RV estimate. Conclusions and Relevance: Mapping of LM and LMM with
      HRCM-RV estimated defects that were similar to but slightly smaller than those
      found in staged excision. Thus, mapping of LM using HRCM-RV can help spare
      healthy tissue by reducing the number of biopsies needed in clinically uncertain
      areas and may be used to plan treatment of LM and LMM and counsel patients
      appropriately.

PMID- 29049432
TI  - Liquid Biopsy in Retinoblastoma.

PMID- 29049433
TI  - Are Surgical Residents Prepared to Care for Transgender Patients?-Reply.

PMID- 29049434
TI  - Survival Outcomes for Patients With T3N0M0 Squamous Cell Carcinoma of the Glottic
      Larynx.
AB  - Importance: Radiotherapy (RT)-based organ preservation approaches for patients
      with advanced laryngeal cancer have been established stepwise through prospective
      randomized clinical trials. However, broad adoption of these approaches has
      stimulated discussion about long-term results challenging their applicability in
      a heterogeneous patient population, most recently for patients with T3 disease.
      Objective: To define outcomes in patients with clinical T3N0M0 glottic laryngeal
      cancer treated with definitive surgical and RT-based approaches. Design, Setting,
      and Participants: This retrospective cohort study included patients treated from
      January 1, 2004, through December 31, 2013, with a median follow-up time of 58
      months (range, 0-126.6 months) in the National Cancer Database. Of the 4003
      patients with T3N0M0 disease, 2622 received definitive therapy defined by the
      study protocol. Data were obtained from the clinical oncology database sourced
      from hospital registry data that are collected from more than 1500 Commission on
      Cancer-accredited facilities. Data were analyzed from September 14, 2016, through
      April 24, 2017. Interventions: Radiotherapy, chemoradiotherapy, surgery, surgery
      and RT, or surgery and chemoradiotherapy. Main Outcomes and Measures: Five-year
      overall survival (OS). Results: A total of 2622 patients (2251 men [85.9%] and
      371 women [14.1%]; median age, 64 years [range, 19-90 years]) were included in
      the analytic cohort. In the overall patient cohort, the adjusted 5-year survival
      probability was 53%. No statistical differences were observed between the primary
      surgery (53%; 95% CI, 48%-57%) and primary RT (54%; 95% CI, 52%-57%) cohorts. In
      multivariate analysis, patient factors associated with decreased OS included age
      (hazard ratio [HR], 1.04; 95% CI, 1.03-1.04), insurance status (HR, 1.26; 95% CI,
      1.06-1.50), and increasing comorbidity (HR, 1.20; 95% CI, 1.02-1.42). Conclusions
      and Relevance: Current management of T3N0M0 glottic laryngeal cancer relies
      largely on RT-based organ preservation approaches. The present study
      substantiates randomized clinical trial data supporting the use of RT-based organ
      preservation approaches for patients with T3N0M0 glottic laryngeal cancer without
      compromising OS.

PMID- 29049435
TI  - Low Rates of Surveillance Imaging After Vascular Surgery Procedures: Should We
      Ask the Patient?

PMID- 29049436
TI  - Minimal Nasolabial Incision Technique for Nasolabial Fold Modification in
      Patients With Facial Paralysis.
AB  - Importance: Creation of symmetrical nasolabial folds (NLFs) is important in the
      management of the paralyzed face. Established techniques use a linear incision in
      the NLF, and technical refinements now allow the linear incision to be omitted.
      Design, Setting, and Participants: This retrospective case series was conducted
      in a tertiary care setting from February 2, 2017, to June 7, 2017. Participants
      were all patients (N = 21) with peripheral facial paralysis who underwent NLF
      modification that used the minimal nasolabial incision technique at the
      Massachusetts Eye and Ear Infirmary Facial Nerve Center from February 1, 2015,
      through August 31, 2016. Main Outcomes and Measures: Patient-reported outcome
      measures using the validated, quality-of-life Facial Clinimetric Evaluation
      (FaCE) Scale; clinician-reported facial function outcomes using a validated
      electronic clinician-graded facial paralysis assessment (eFACE); layperson
      assessment of the overall aesthetic outcome of the NLF; and expert-clinician scar
      assessment of the NLF. Results: Of the 21 patients who underwent NLF modification
      that used the minimal nasolabial incision technique, 9 patients (43%) were female
      and 12 (57%) were male. The mean age was 41 (range, 9-90) years; 17 patients
      (81%) were adults (>=18 years) and 4 (19%) were children (<18 years). Overall,
      significant improvements were observed after NLF modification in all outcome
      measures as graded by both clinicians and patients. The mean (SD) scores for
      total eFACE were 60.7 (14.9) before the operation and 77.2 (8.9) after the
      operation (mean difference, 16.5 [95% CI, 8.5-24.2]; P < .001). The mean (SD)
      static eFACE scores were 61.4 (20.6) before the operation and 82.7 (12.4) after
      the operation (mean difference, 21.3 [95% CI, 10.7-31.9]; P < .001). The mean
      (SD) FaCE quality-of-life scores were 51.3 (20.1) before the operation and 70.3
      (12.6) after the operation (mean difference, 19.0 [95% CI, 6.5-31.6]; P  = 
      .001). The layperson self-assessment of the overall aesthetic outcome of the NLF
      modification was higher among the group who had the minimal nasolabial incision
      than it was for the group who had a historical nasolabial incision (mean [SD],
      68.17 [13.59] vs 56.28 [13.60]; mean difference, 11.89 [95% CI, 3.81-19.97]; P <
      .001). Similarly, the expert-clinician scar assessment of the NLF modification
      was higher for the group who had the minimal nasolabial incision than it was for
      the group who had a historical nasolabial incision (3.78 [0.91] vs 2.98 [0.81];
      mean difference, 0.80 [95% CI, 0.29-1.32]; P  =  .007). Conclusions and
      Relevance: The minimal nasolabial incision technique for NLF modification is
      effective in rehabilitating the NLF in facial paralysis without adding a long
      linear scar to the central midface. Level of Evidence: 4.

PMID- 29049438
TI  - Mood Instability and Reward Dysregulation-A Neurocomputational Model of Bipolar
      Disorder.

PMID- 29049439
TI  - Environmental Exposures, Telomere Length at Birth, and Disease Susceptibility in
      Later Life.

PMID- 29049437
TI  - Progression of Stargardt Disease as Determined by Fundus Autofluorescence in the
      Retrospective Progression of Stargardt Disease Study (ProgStar Report No. 9).
AB  - Importance: Sensitive outcome measures for disease progression are needed for
      treatment trials of Stargardt disease. Objective: To describe the yearly
      progression rate of atrophic lesions in the retrospective Progression of
      Stargardt Disease study. Design, Setting, and Participants: A multicenter
      retrospective cohort study was conducted at tertiary referral centers in the
      United States and Europe. A total of 251 patients aged 6 years or older at
      baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in
      the study from 9 centers between August 2, 2013, and December 12, 2014; of these
      patients, 215 had at least 2 gradable fundus autofluorescence images with
      atrophic lesion(s) present in at least 1 eye. Exposures: Areas of definitely
      decreased autofluorescence (DDAF) and questionably decreased autofluorescence
      were quantified by a reading center. Progression rates were estimated from linear
      mixed models with time as the independent variable. Main Outcomes and Measures:
      Yearly rate of progression using the growth of atrophic lesions measured by
      fundus autofluorescence. Results: A total of 251 participants (458 study eyes)
      were enrolled. Images from 386 eyes of 215 participants (126 females and 89
      males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9
      [13.3] years) showed atrophic lesions present on at least 2 visits and were
      graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224
      eyes (123 female participants and 101 male participants; mean [SD] age, 33.0
      [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were
      included in the estimation of the progression of the area of DDAF. At the first
      visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2
      (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and
      questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean
      progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total
      decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates
      of progression depended on the initial size of the lesion. Conclusions and
      Relevance: In Stargardt disease with DDAF lesions, fundus autofluorescence may
      serve as a monitoring tool for interventional clinical trials that aim to slow
      disease progression. Rates of progression depended mainly on initial lesion size.

PMID- 29049440
TI  - Treatment of Acute Upper Airway Obstruction-Reply.

PMID- 29049441
TI  - Tonsillectomy for Obstructive Sleep-Disordered Breathing or Recurrent Throat
      Infection in Children: Summary of AHRA Comparative Effectiveness Review.

PMID- 29049442
TI  - Pustular Eruption in a Patient With Cancer Treated With Complementary and
      Alternative Medicine.

PMID- 29049443
TI  - The Most Beautiful People: Evolving Standards of Beauty.

PMID- 29049444
TI  - Patient Perceptions About Their Physician in 2 Words: The Good, the Bad, and the
      Ugly.

PMID- 29049445
TI  - Error in Conflicts of Interest Disclosures.

PMID- 29049446
TI  - Association of Socioeconomics With Prevalence of Visual Impairment and Blindness.
AB  - Importance: Vision loss is the third most common impairment worldwide. Although
      cost-effective interventions are available for preventing or curing most causes
      of vision loss, availability of these interventions varies considerably between
      countries and districts. Knowledge of the association between vision loss and
      socioeconomic factors is informative for public health planning. Objectives: To
      explore correlations of the prevalence of visual impairment with socioeconomic
      factors at country levels and to model and estimate a socioeconomic-adjusted
      disease burden based on these data. Design, Setting, and Participants: In this
      cross-sectional study, the following data were collected from 190 countries and
      territories: the age-standardized prevalence of moderate to severe visual
      impairment (MSVI) and blindness from January 1 to December 31, 2010, across
      countries, human development index (HDI), gross domestic product (GDP) per
      capita, total health expenditure, total health expenditure as percentage of GDP
      (total health expenditure/GDP), public health expenditure as percentage of total
      health expenditure (public/total health expenditure), and out-of-pocket
      expenditure as percentage of total health expenditure (out-of-pocket/total health
      expenditure). Countries were divided into 4 levels (low, medium, high, and very
      high) by HDI. Data analysis was conducted from September 1, 2016, to July 1,
      2017. Main Outcomes and Measures: The correlations between prevalence data and
      socioeconomic indices were assessed. Results: A strong negative association
      between prevalence rates of MSVI and blindness and socioeconomic level of
      development was observed. The mean (SD) age-standardized prevalence of MSVI
      decreased from 4.38% (1.32%) in low-HDI regions to 1.51% (1.00%) in very-high-HDI
      regions (P < .001). The national HDI level was attributable to 56.3% of global
      variation in prevalence rates of MSVI and 67.1% of global variation in prevalence
      rates of blindness. Higher prevalence rates were also associated with lower total
      health expenditure per capita, total health expenditure/GDP (beta = -0.236 [95%
      CI, -0.315 to -0.157] for prevalence of MSVI; beta = -0.071 [95% CI, -0.100 to 
      0.042] for prevalence of blindness), public/total health expenditure (beta = 
      0.041 [95% CI, -0.052 to -0.031] for prevalence of MSVI; beta = -0.014 [95% CI, 
      0.018 to -0.010] for prevalence of blindness), and higher percentage of out-of
      pocket/total health expenditure (beta = 0.044 [95% CI, 0.032-0.055] for
      prevalence of MSVI; beta = 0.013 [95% CI, 0.009-0.017] for prevalence of
      blindness). Countries with increased burden of visual impairment and blindness
      can be easily identified by the results of the linear models. Socioeconomic
      factors could explain 69.4% of the global variations in prevalence of MSVI and
      76.3% of the global variations in prevalence of blindness. Conclusions and
      Relevance: Burden of visual impairment and socioeconomic indicators were closely
      associated and may help to identify countries requiring greater attention to
      these issues. The regression modeling described may provide an opportunity to
      estimate appropriate public health targets that are consistent with a country's
      level of socioeconomic development.

PMID- 29049447
TI  - A Case of Unexpected Adult-Onset Neurologic Decline in CLN3-Associated Retinal
      Degeneration.

PMID- 29049448
TI  - All Thiopurines Are Equal But Some Thiopurines Are More Equal Than Others-Reply.

PMID- 29049449
TI  - Increasing Evidence for an Association Between Amyotrophic Lateral Sclerosis and
      Psychiatric Disorders.

PMID- 29049451
TI  - When Should Patients Be Involved in Cardiovascular Clinical Trial Design?:
      Always, Early, and Often.

PMID- 29049450
TI  - Dual-Task Gait and Incident Dementia: A Step Forward, but Not There Yet.

PMID- 29049452
TI  - HSD3B1 and Response to a Nonsteroidal CYP17A1 Inhibitor in Castration-Resistant
      Prostate Cancer.
AB  - Importance: The HSD3B1 (1245C) germline variant encodes for a gain-of-function
      missense in 3beta-hydroxysteroid dehydrogenase isoenzyme 1 (3betaHSD1) that
      results in increased dihydrotestosterone synthesis from extragonadal precursors
      and is predictive of more rapid progression to castration-resistant prostate
      cancer (CRPC). Objective: To determine whether the HSD3B1 (1245C) genotype is
      predictive of clinical response to extragonadal androgen ablation with
      nonsteroidal 17alpha-hydroxylase/17,20-lyase (CYP17A1) inhibition in men with
      metastatic CRPC. Design, Setting, and Participants: An observational study of men
      with metastatic CRPC treated with ketoconazole between June 1998 and December
      2012 was conducted at the University of California, San Francisco. Exposures:
      Extragonadal androgen ablation with the nonsteroidal CYP17A1 inhibitor
      ketoconazole among men with metastatic CRPC. Main Outcomes and Measures: The
      primary end points of analysis were duration of ketoconazole therapy and time to
      disease progression stratified by HSD3B1 genotype. Disease progression was
      defined as either biochemical or radiographic progression, using the Prostate
      Cancer Working Group 3 and Response Evaluation Criteria in Solid Tumors (RECIST)
      version 1.1 definitions, respectively. Kaplan-Meier analysis was used to estimate
      time on therapy and time to disease progression. A log-rank test for trend was
      used to compare outcomes by HSD3B1 genotype. Results: A total of 90 men (median
      [interquartile range] age, 61.5 [55.3-67.0] years) with metastatic CRPC were
      included in the analysis, with sufficient data to determine duration of
      ketoconazole therapy and time to disease progression in 88 and 81 patients,
      respectively. The median duration of therapy increased with the number of
      inherited HSD3B1 (1245C) variant alleles: 5.0 months (95% CI, 3.4-10.4) for 0
      variant alleles; 7.5 months (95% CI, 4.9-19.2) for 1; and 12.3 months (95% CI,
      1.8-not reached) for 2 (overall comparison for trend, P = .01). Median
      progression-free survival also increased with number of HSD3B1 (1245C) variant
      alleles inherited: 5.4 months (95% CI, 3.7-7.5) for 0 variant alleles; 9.7 months
      (95% CI, 5.6-32.9) for 1; and 15.2 months (95% CI, 7.8-not reached) for 2
      (overall comparison for trend, P = .03). Conclusions and Relevance: Inheritance
      of the HSD3B1 (1245C) variant allele, which is a predictive biomarker of
      resistance to castration, is also a predictive biomarker of sensitivity to
      extragonadal androgen ablation with a nonsteroidal CYP17A1 inhibitor. These
      findings signal a possible pathway of treatment stratification for patients with
      prostate cancer.

PMID- 29049453
TI  - Association of Endogenous Endophthalmitis With Intravenous Drug Use: An Emerging
      Public Health Challenge.

PMID- 29049455
TI  - The Role of Optical Coherence Tomography Angiography in Polypoidal Choroidal
      Vasculopathy.

PMID- 29049454
TI  - Association of Mitochondrial DNA Copy Number With Cardiovascular Disease.
AB  - Importance: Mitochondrial dysfunction is a core component of the aging process
      and may play a key role in atherosclerotic cardiovascular disease. Mitochondrial
      DNA copy number (mtDNA-CN), which represents the number of mitochondria per cell
      and number of mitochondrial genomes per mitochondrion, is an indirect biomarker
      of mitochondrial function. Objective: To determine whether mtDNA-CN, measured in
      an easily accessible tissue (buffy coat/circulating leukocytes), can improve risk
      classification for cardiovascular disease (CVD) and help guide initiation of
      statin therapy for primary prevention of CVD. Design, Setting, and Participants:
      Prospective, population-based cohort analysis including 21 870 participants (20
      163 free from CVD at baseline) from 3 studies: Cardiovascular Health Study (CHS),
      Atherosclerosis Risk in Communities Study (ARIC), and Multiethnic Study of
      Atherosclerosis (MESA). The mean follow-up was 13.5 years. The study included 11
      153 participants from ARIC, 4830 from CHS, and 5887 from MESA. Analysis of the
      data was conducted from March 10, 2014, to January 29, 2017. Exposures:
      Mitochondrial DNA-CN measured from buffy coat/circulating leukocytes. Main
      Outcomes and Measures: Incident CVD, which combines coronary heart disease,
      defined as the first incident myocardial infarction or death owing to coronary
      heart disease, and stroke, defined as the first nonfatal stroke or death owing to
      stroke. Results: Of the 21 870 participants, the mean age was 62.4 years (ARIC,
      57.9 years; MESA, 62.4 years; and CHS, 72.5 years), and 54.7% of participants
      were women. The hazard ratios for incident coronary heart disease, stroke, and
      CVD associated with a 1-SD decrease in mtDNA-CN were 1.29 (95% CI, 1.24-1.33),
      1.11 (95% CI, 1.06-1.16), and 1.23 (95% CI, 1.19-1.26). The associations
      persisted after adjustment for traditional CVD risk factors. Addition of mtDNA-CN
      to the 2013 American College of Cardiology/American Heart Association Pooled
      Cohorts Equations for estimating 10-year hard atherosclerosis CVD risk was
      associated with improved risk classification (continuous net reclassification
      index, 0.194; 95% CI, 0.130-0.258; P < .001). Mitochondrial DNA-CN further
      improved sensitivity and specificity for the 2013 American College of
      Cardiology/American Heart Association recommendations on initiating statin
      therapy for primary prevention of ASCVD (net 221 individuals appropriately
      downclassified and net 15 individuals appropriately upclassified). Conclusions
      and Relevance: Mitochondrial DNA-CN was independently associated with incident
      CVD in 3 large prospective studies and may have potential clinical utility in
      improving CVD risk classification.

PMID- 29049456
TI  - Acute Bilateral Eyelid Edema in a 3-Year-Old Girl With Pyuria.

PMID- 29049459
TI  - Telangiectasias on the Lower Extremity.

PMID- 29049457
TI  - Association of Patient Frailty With Increased Morbidity After Common Ambulatory
      General Surgery Operations.
AB  - Importance: Frailty is a measure of decreased physiological reserve that is
      associated with morbidity and mortality in major elective and emergency general
      surgery operations, independent of chronological age. To date, the association of
      frailty with outcomes in ambulatory general surgery has not been established.
      Objective: To determine the association between frailty and perioperative
      morbidity in patients undergoing ambulatory general surgery operations. Design,
      Setting, and Participants: A retrospective cohort study was conducted of 140 828
      patients older than 40 years of age from the 2007-2010 American College of
      Surgeons National Surgical Quality Improvement Program Participant Use File who
      underwent ambulatory and 23-hour-stay hernia, breast, thyroid, or parathyroid
      surgery. Data analysis was performed from August 18, 2016, to June 21, 2017. Main
      Outcomes and Measures: The association between the National Surgical Quality
      Improvement Program modified frailty index and perioperative morbidity was
      determined via multivariable logistic regression with random-effects modeling to
      control for clustering within Current Procedural Terminology codes. Results: A
      total of 140 828 patients (80 147 women and 60 681 men; mean [SD] age, 59.3
      [12.0] years) underwent ambulatory hernia (n = 71 455), breast (n = 51 267),
      thyroid, or parathyroid surgery (n = 18 106). Of these patients, 2457 (1.7%)
      experienced any type of perioperative complication and 971 (0.7%) experienced
      serious perioperative complications. An increasing modified frailty index was
      associated with a stepwise increase in the incidence of complications. In
      multivariable analysis adjusting for age, sex, race/ethnicity, anesthesia type,
      tobacco use, renal failure, corticosteroid use, and clustering by Current
      Procedural Terminology codes, an intermediate modified frailty index score (0.18
      0.35, corresponding to 2-3 frailty traits) was associated with statistically
      significant odds ratios of 1.70 (95% CI, 1.54-1.88; P < .001) for any
      complication and 2.00 (95% CI, 1.72-2.34; P < .001) for serious complications. A
      high modified frailty index score (>=0.36, corresponding to >=4 frailty traits)
      was associated with statistically significant odds ratios of 3.35 (95% CI, 2.52
      4.46; P < .001) for any complication and 3.95 (95% CI, 2.65-5.87; P < .001) for
      serious complications. Anesthesia with local and monitored anesthesia care was
      the only modifiable covariate associated with decreased odds of serious 30-day
      complications, with an adjusted odds ratio of 0.66 (95% CI, 0.53-0.81; P < .001).
      Conclusions and Relevance: Frailty is associated with increased perioperative
      morbidity in common ambulatory general surgery operations, independent of age,
      type of anesthesia, and other comorbidities. Surgeons should consider frailty
      rather than chronological age when counseling and selecting patients for elective
      ambulatory surgery.

PMID- 29049458
TI  - Long-term Outcomes of Multiple Arterial Coronary Artery Bypass Grafting: A
      Population-Based Study of Patients in British Columbia, Canada.
AB  - Importance: Although the long-term survival advantage of multiple arterial
      grafting (MAG) vs the standard use of left internal thoracic artery (LITA)
      supplemented by saphenous vein grafts (LITA+SVG) has been demonstrated in several
      observational studies, to our knowledge its safety and other long-term clinical
      benefits in a large, population-based cohort are unknown. Objective: To compare
      the safety and long-term outcomes of MAG vs LITA+SVG among overall and selected
      subgroups of patients. Design, Setting, and Participants: In this population
      based observational study, we included 20 076 adult patients with triple-vessel
      or left-main disease who underwent primary isolated coronary artery bypass
      grafting (MAG, n = 5580; LITA+SVG, n = 14 496) in the province of British
      Columbia, Canada, from January 2000 to December 2014, with follow-up to December
      2015. We performed propensity-score analyses by weighting and matching and
      multivariable Cox regression to minimize treatment selection bias. Exposures:
      Multiple arterial grafting or LITA+SVG. Main Outcomes and Measures: Mortality,
      repeated revascularization, myocardial infarction, heart failure, and stroke.
      Results: Of 5580 participants who underwent MAG, 586 (11%) were women and the
      mean (SD) age was 60 (8.7) years. Of 14 496 participants who underwent LITA+SVG,
      2803 (19%) were women and the mean (SD) age was 68 (8.9) years. The median
      (interquartile range) follow-up time was 9.1 (5.1-12.6) years and 8.1 (4.5-11.7)
      years for the groups receiving MAG and LITA+SVG, respectively. Compared with
      LITA+SVG, MAG was associated with reduced mortality rates (hazard ratio [HR],
      0.79; 95% CI, 0.72-0.87) and repeated revascularization rates (HR, 0.74; 95% CI,
      0.66-0.84) in 15-year follow-up and reduced incidences of myocardial infarction
      (HR, 0.63; 95% CI, 0.47-0.85) and heart failure (HR, 0.79; 95% CI, 0.64-0.98) in
      7-year follow-up. The long-term benefits were coherent by all 3 statistical
      methods and persisted among patient subgroups with diabetes, obesity, moderately
      impaired ejection fraction, chronic obstructive pulmonary disease, peripheral
      vascular disease, or renal disease. Multiple arterial grafting was not associated
      with increased morbidity or mortality rates at 30 days overall or within patient
      subgroups. Conclusions and Relevance: Compared with LITA+SVG, MAG is associated
      with reduced mortality, repeated revascularization, myocardial infarction, and
      heart failure among patients with multivessel disease who are undergoing coronary
      artery bypass grafting without increased mortality or other adverse events at 30
      days. The long-term benefits consistently observed across multiple outcomes and
      subgroups support the consideration of MAG for a broader spectrum of patients who
      are undergoing coronary artery bypass grafting in routine practice.

PMID- 29049461
TI  - Incorrect Trial Database Number.

PMID- 29049460
TI  - Mild Traumatic Brain Injury and Mental Health.

PMID- 29049462
TI  - Association of Surgical Approach and Margin Status With Oncologic Outcomes
      Following Gross Total Resection for Sinonasal Melanoma.

PMID- 29049463
TI  - Prevalence of Age-Related Macular Degeneration in Australia: The Australian
      National Eye Health Survey.
AB  - Importance: Age-related macular degeneration (AMD) is a leading cause of
      irreversible blindness among the elderly population globally. Currently,
      knowledge of the epidemiology of AMD in Australia remains scarce because of a
      paucity of recent population-based data. Objective: To examine the prevalence of
      AMD in Australia. Design, Setting, and Participants: In this population-based,
      cross-sectional survey performed from March 11, 2015, to April 18, 2016, a sample
      of 3098 nonindigenous Australians 50 years and older and 1738 indigenous
      Australians 40 years and older from 30 geographic areas across Australia were
      examined. Main Outcomes and Measures: Any AMD, early AMD, intermediate AMD, and
      late AMD graded according to the Beckman clinical classification system. Results:
      A total of 4836 individuals were examined, including 3098 nonindigenous
      Australian (64.1%; 58.9% female vs 41.1% male; age range, 40-92 years; mean [SD]
      age, 55.0 [10.0] years) and 1738 indigenous Australians (35.9%; 53.6% female vs
      46.4% male; age range, 50-98 years; mean [SD] age, 66.6 [9.7] years). A total of
      4589 (94.9%, 2946 nonindigenous and 1643 indigenous) participants had retinal
      photographs in at least 1 eye that were gradable for AMD. The weighted prevalence
      of early AMD was 14.8% (95% CI, 11.7%-18.6%) and of intermediate AMD was 10.5%
      (95% CI, 8.3%-13.1%) among nonindigenous Australians. In indigenous Australians,
      the weighted prevalence of early AMD was 13.8% (95% CI, 9.7%-19.3%) and of
      intermediate AMD was 5.7% (96% CI, 4.7%-7.0%). Late AMD was found in 0.96% (95%
      CI, 0.59%-1.55%) of nonindigenous participants (atrophic, 0.72%; neovascular,
      0.24%). The prevalence of late AMD increased to 6.7% in participants 80 years or
      older and was higher in men (1.4% vs 0.61%, P = .02). Only 3 (0.17% [95% CI,
      0.04%-0.63%]) indigenous participants had late (atrophic) AMD. Age-related
      macular degeneration was attributed as the main cause of vision loss (<6/12 in
      the better eye) in 23 of 208 nonindigenous Australians (11.1%) and 2 of 183
      indigenous Australians (1.1%). Conclusions and Relevance: In line with data from
      other white populations, AMD is a prominent cause of vision loss in the
      nonindigenous Australian population. An increased provision of low vision
      rehabilitation services may be required to cope with the projected increase in
      AMD in Australia.

PMID- 29049465
TI  - Pregnancy and Subsequent Glucose Intolerance in Women of Childbearing Age:
      Heeding the Early Warning Signs for Primary Prevention of Cardiovascular Disease
      in Women.

PMID- 29049464
TI  - Clustering of Neuropsychiatric Disease in First-Degree and Second-Degree
      Relatives of Patients With Amyotrophic Lateral Sclerosis.
AB  - Importance: Amyotrophic lateral sclerosis (ALS) is a progressive
      neurodegenerative condition primarily involving the motor system. There is
      increasing epidemiologic evidence of an association between ALS and a wider
      spectrum of neurodegenerative and neuropsychiatric disorders among family
      members, including schizophrenia and psychotic illness and suicidal behavior.
      Objective: To examine the frequency and range of neuropsychiatric conditions that
      occur within individual first-degree and second-degree relatives of patients with
      ALS. Design, Setting, and Participants: In this population-based, case-control
      family aggregation study, all 202 patients included in the Irish ALS Register
      between January 1, 2012, and January 31, 2014, with definite, probable, or
      possible ALS as defined by El Escorial criteria were invited to participate. A
      total of 75 patients were unable or refused to participate and were excluded; the
      remaining 127 patients with incident ALS were genotyped for the C9orf72 repeat
      expansion and 132 age- and sex-matched controls were included in the study. Main
      Outcome and Measures: The prevalence of defined neuropsychiatric disease in first
      degree and second-degree relatives of patients with ALS and matched controls was
      determined. Results: Mean (SD) age at diagnosis of the 127 patients in the study
      (58 women and 69 men) was 64.2 (10.7) years. Data from 2116 relatives of patients
      with ALS were reported, including 924 first-degree relatives, 1128 second-degree
      relatives, and 64 third-degree relatives. Data from controls were reported from
      829 first-degree and 1310 second-degree relatives. A total of 77 patients with
      ALS (61.4%) and 51 control participants (38.6%) reported at least 1 first-degree
      or second-degree relative with a history of schizophrenia, psychosis, suicide,
      depression, alcoholism, or autism (relative risk [RR], 1.50; 95% CI, 1.08-2.17; P
      = .02). Cluster analysis suggested the following 2 subgroups based on the number
      of family members with a neuropsychiatric condition: expected (0-2) and high
      (>=3). Within the high subgroup, ALS kindreds presented a significantly higher
      rate of psychiatric illness than did controls (28 of 39 [71.8%]; mean [SD] number
      of siblings, 4.29 [1.41]; P = .001). A strong family history of schizophrenia
      (RR, 3.40; 95% CI, 1.27-9.30; P = .02), suicide (RR, 3.30; 95% CI, 1.07-10.05; P
      = .04), autism (RR, 10.10; 95% CI, 1.30-78.80; P = .03), and alcoholism (RR,
      1.48; 95% CI, 1.01-2.17; P = .045) was reported in ALS kindreds. A total of 5 of
      29 probands (17.2%) with a strong family history of neuropsychiatric conditions
      (>=3 first-degree or second-degree relatives) carried the C9orf72 repeat
      expansion. Conclusions and Relevance: Neuropsychiatric symptoms in addition to
      schizophrenia, including obsessive-compulsive disorder, autism, and alcoholism,
      occur more frequently in ALS kindreds than in controls. The presence of the
      C9orf72 repeat expansion does not fully account for this finding, suggesting the
      presence of additional pleiotropic genes associated with both ALS and
      neuropsychiatric disease in the Irish population.

PMID- 29049466
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Systematic Review.
AB  - Importance: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL),
      a rare peripheral T-cell lymphoma, is increasing in incidence. However, many
      practitioners who treat patients with breast cancer are not aware of this
      disease. Objectives: To assess how BIA-ALCL develops, its risk factors,
      diagnosis, and subsequent treatment and to disseminate information about this
      entity to the medical field. Evidence Review: A literature review was performed
      in an academic medical setting. All review articles, case reports, original
      research articles, and any other articles relevant to BIA-ALCL were included.
      Data on BIA-ALCL, such as pathophysiology, patient demographics, presentation,
      diagnosis, treatment, and outcomes, were extracted. Particular focus was paid to
      age, time to onset, implant type, initial symptoms, treatment, and survival. The
      search was conducted in January 2017 for studies published in any year. Findings:
      After duplicates were excluded, 304 relevant articles were assessed, and 115 were
      included from the first documented case in August 1997 through January 2017.
      Thirty review articles, 44 case reports or series, 15 original research articles,
      and 26 "other" articles (eg, techniques, special topics, letters) were reviewed.
      A total of 93 cases have been reported in the literature, and with the addition
      of 2 unreported cases from the Penn State Health Milton S. Hershey Medical
      Center, 95 patients were included in this systematic review. Almost all
      documented BIA-ALCL cases have been associated with a textured device. The
      underlying mechanism is thought to be due to chronic inflammation from indolent
      infections, leading to malignant transformation of T cells that are anaplastic
      lymphoma kinase (ALK) negative and CD30 positive. The mean time to presentation
      is approximately 10 years after implant placement, with 55 of 83 (66%) patients
      initially seen with an isolated late-onset seroma and 7 of 83 (8%) with an
      isolated new breast mass. Ultrasonography with fluid aspiration can be used for
      diagnosis. Treatment must include removal of the implant and surrounding capsule.
      More advanced disease may require chemotherapy, radiotherapy, and lymph node
      dissection. Conclusions and Relevance: Breast implant-associated anaplastic large
      cell lymphoma is a rare cancer in patients with breast implants but is increasing
      in incidence. It is important for all physicians involved in the care of patients
      with breast implants to be aware of this entity and be able to recognize initial
      symptoms.

PMID- 29049467
TI  - Updated Cost-effectiveness Assessments of PCSK9 Inhibitors From the Perspectives
      of the Health System and Private Payers: Insights Derived From the FOURIER Trial.
AB  - Importance: Preliminary cost-effectiveness analyses of proprotein convertase
      subtilisin/kexin type 9 inhibitor (PCSK9i) were based on benefits estimated from
      reductions in low-density lipoprotein cholesterol that occurred in PCSK9i trials
      with variable results. The recent Further Cardiovascular Outcomes Research with
      PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial provides better
      information about the effectiveness of the drug. Objective: To use the trial
      results to determine the cost-effectiveness of a PCSK9i and statin treatment
      strategy compared with a statin alone strategy. Design, Setting, and
      Participants: We derived observed rates of events, outcomes, cost of care, and
      health insurance from existing literature for a theoretical cohort of patients
      designed to resemble the FOURIER PCSK9i trial population and created a Markov
      model during the time horizon of a full lifetime. Main Outcomes and Measures: We
      evaluated the incremental cost-effectiveness ratio from a health system
      perspective, and the return on investment from a private payer perspective. For
      both measures, we assumed an annual PCSK9i drug price of $14 300, with a lapse in
      US patent protection that would reduce the price by 43% in year 12. Costs were
      reported in 2016 US dollars. Results: This study modeled 1000 hypothetical
      patients with attributes similar to those of the FOURIER trial cohort. At the
      current price, the incremental cost-effectiveness ratio of statin plus PCSK9i
      therapy was $337 729 per quality-adjusted life-year. Our probabilistic
      sensitivity analysis found that a statin plus PCSK9i strategy had a low
      probability (<1%) of being cost effective at the commonly accepted societal
      threshold of $100 000 per quality-adjusted life-year. Furthermore, PCSK9i
      produced a negative return on investment of 86% for private payers. In our
      threshold analysis, the price of PCSK9i would need to drop 62%, to $5459 per
      year, to reach $100 000 per quality-adjusted life year. Conclusions and
      Relevance: At current prices, the addition of PCSK9i to statin therapy is
      estimated to provide an additional quality-adjusted life year for $337 729 .
      Significant discounts are necessary to meet conventional cost-effectiveness
      standards.

PMID- 29049468
TI  - Nationwide Variation in Rates of Thyroidectomy Among US Medicare Beneficiaries.
AB  - Importance: Research on variation in rates of procedures across otherwise similar
      geographic regions provides vital insight into practice patterns. It reveals the
      degree of consensus on how a particular condition is managed, shows areas where
      access to care may be inadequate, and other areas where the population may be
      receiving inappropriately high levels of care. Objective: To test the hypothesis
      that rates of thyroid surgery vary across US geographic regions. Design, Setting,
      and Participants: A cross-sectional analysis of Medicare data for 15 888
      beneficiaries aged 65 years or older from 2014 was carried out. Main Outcome and
      Measures: Overall and hospital referral region-specific thyroidectomy rate per
      100 000 Medicare beneficiaries. Results: In 2014, 15 888 thyroidectomies were
      performed on Medicare beneficiaries in the United States (partial n = 7506, total
      n = 8382), representing a national average rate of 60 per 100 000 beneficiaries
      (median, 59 per 100 000 beneficiaries; IQR, 43-70 per 100 000). A 6.2-fold
      difference in thyroidectomy rates was observed across US regions (range, 22-139
      per 100 000 Medicare beneficiaries). Conclusions and Relevance: Thyroidectomy
      rates in the United States vary 6.2 fold, more than prostatectomy rates, which
      are usually held as the example of the procedure with the widest variation in the
      United States. This wide variation in thyroidectomy rates observed among Medicare
      beneficiaries suggests widely divergent local beliefs and practice patterns
      surrounding the management of thyroid nodules and cancer because rates appeared
      to be unrelated to health care availability, regional socioeconomic status, or
      surgeons per capita. A better understanding for the reasons underlying this
      variation is needed.

PMID- 29049470
TI  - Race/Ethnicity-Based Outcomes in Cardiovascular Medicine.

PMID- 29049469
TI  - Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine
      Naloxone for Opioid Dependence: A Randomized Clinical Noninferiority Trial.
AB  - Importance: To date, extended-release naltrexone hydrochloride has not previously
      been compared directly with opioid medication treatment (OMT), currently the most
      commonly prescribed treatment for opioid dependence. Objective: To determine
      whether treatment with extended-release naltrexone will be as effective as daily
      buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence
      from heroin and other illicit substances in newly detoxified individuals. Design,
      Setting and Participants: A 12-week, multicenter, outpatient, open-label
      randomized clinical trial was conducted at 5 urban addiction clinics in Norway
      between November 1, 2012, and December 23, 2015; the last follow-up was performed
      on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria)
      individuals were recruited from outpatient addiction clinics and detoxification
      units and assessed for eligibility. Intention-to-treat analyses of efficacy end
      points were performed with all randomized participants. Interventions:
      Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24
      mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered
      intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures:
      Primary end points (protocol) were the randomized clinical trial completion rate,
      the proportion of opioid-negative urine drug tests, and number of days of use of
      heroin and other illicit opioids. Secondary end points included number of days of
      use of other illicit substances. Safety was assessed by adverse event reporting.
      Results: Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%)
      were women. Eighty individuals were randomized to extended-release naltrexone and
      79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the
      extended-release naltrexone group was noninferior to the buprenorphine-naloxone
      group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time
      of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test).
      Treatment with extended-release naltrexone showed noninferiority to buprenorphine
      naloxone on group proportion of total number of opioid-negative urine drug tests
      (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, 
      0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9
      to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, 
      4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of
      heroin and other illicit opioids in the extended-release naltrexone group. No
      significant differences were found between the treatment groups regarding most
      other illicit substance use. Conclusions and Relevance: Extended-release
      naltrexone was as effective as buprenorphine-naloxone in maintaining short-term
      abstinence from heroin and other illicit substances and should be considered as a
      treatment option for opioid-dependent individuals. Trial Registration:
      clinicaltrials.gov Identifier: NCT01717963.

PMID- 29049471
TI  - Firearm-Related Injury and Death: A US Health Care Crisis in Need of Health Care
      Professionals.

PMID- 29049472
TI  - Underlying Factors in Drug Overdose Deaths.

PMID- 29049473
TI  - The Concertina Case of Ventricular Preexcitation.

PMID- 29049474
TI  - Virtual Surgery for the Nasal Airway: A Preliminary Report on Decision Support
      and Technology Acceptance.
AB  - Importance: Nasal airway obstruction (NAO) is a common problem that affects
      patient quality of life. Surgical success for NAO correction is variable. Virtual
      surgery planning via computational fluid dynamics (CFD) has the potential to
      improve the success rates of NAO surgery. Objective: To elicit surgeon feedback
      of a virtual surgery planning tool for NAO and to determine if this tool affects
      surgeon decision making. Design, Setting, and Participants: For this cross
      sectional study, 60-minute face-to-face interviews with board-certified
      otolaryngologists were conducted at a single academic otolaryngology department
      from September 16, 2016, through October 7, 2016. Virtual surgery methods were
      introduced, and surgeons were able to interact with the virtual surgery planning
      tool interface. Surgeons were provided with a patient case of NAO, and open
      feedback of the platform was obtained, with emphasis on surgical decision making.
      Main Outcomes and Measures: Likert scale responses and qualitative feedback were
      collected for the virtual surgery planning tool and its influence on surgeon
      decision making. Results: Our 9 study participants were all male, board-certified
      otolaryngologists with a mean (range) 15 (4-28) number of years in practice and a
      mean (range) number of nasal surgeries per month at 2.2 (0.0-6.0). When examined
      on a scale of 1 (not at all) to 5 (completely), surgeon mean (SD) score was 3.4
      (0.5) for how realistic the virtual models were compared with actual surgery. On
      the same scale, when asked how much the virtual surgery planning tool changed
      surgeon decision making, mean (SD) score was 2.6 (1.6). On a scale of 1 (strongly
      disagree) to 7 (strongly agree), surgeon scores for perceived usefulness of the
      technology and attitude toward using it were 5.1 (1.1) and 5.7 (0.9),
      respectively. Conclusions and Relevance: Our study shows positive surgeon
      experience with a virtual surgery planning tool for NAO based on CFD simulations.
      Surgeons felt that future applications and areas of study of the virtual surgery
      planning tool include its potential role for patient counseling, selecting
      appropriate surgical candidates, and identifying which anatomical structures
      should be targeted for surgical correction. Level of Evidence: NA.

PMID- 29049476
TI  - Machine Learning Models for Prediction of Reinjury After Penetrating Trauma.

PMID- 29049475
TI  - Potential of Aqueous Humor as a Surrogate Tumor Biopsy for Retinoblastoma.
AB  - Importance: Retinoblastoma (Rb) is one of the first tumors to have a known
      genetic etiology. However, because biopsy of this tumor is contraindicated, it
      has not been possible to define the effects of secondary genetic changes on the
      disease course. Objective: To investigate whether the aqueous humor (AH) of Rb
      eyes has sufficient tumor-derived DNA to perform genetic analysis of the tumor,
      including DNA copy number alterations. Design, Setting, and Participants: This
      investigation was a case series study at a tertiary care hospital (Children's
      Hospital Los Angeles) with a large Rb treatment center. Cell-free DNA (cfDNA) was
      isolated from 6 AH samples from 3 children with Rb, including 2 after primary
      enucleation and 1 undergoing multiple intravitreous injections of melphalan for
      vitreous seeding. Samples were taken between December 2014 and September 2015.
      Main Outcomes and Measures: Measurable levels of nucleic acids in the AH and
      identification of tumor-derived DNA copy number variation in the AH. The AH was
      analyzed for DNA, RNA, and micro-RNA using Qubit high-sensitivity kits. Cell-free
      DNA was isolated from the AH, and sequencing library protocols were optimized.
      Shallow whole-genome sequencing was performed on an Illumina platform, followed
      by genome-wide chromosomal copy number variation profiling to assess the presence
      of tumor DNA fractions in the AH cfDNA of the 3 patients. One child's cfDNA from
      the AH and tumor DNA were subjected to Sanger sequencing to isolate the RB1
      mutation. Results: Six AH samples were obtained from 3 Rb eyes in 3 children (2
      male and 1 female; diagnosed at ages 7, 20, and 28 months). A corroborative
      pattern between the chromosomal copy number variation profiles of the AH cfDNA
      and tumor-derived DNA from the enucleated samples was identified. In addition, a
      nonsense RB1 mutation (Lys->STOP) from 1 child was also identified from the AH
      samples obtained during intravitreous injection of melphalan, which matched the
      tumor sample postsecondary enucleation. Sanger sequencing of the AH cfDNA and
      tumor DNA with polymerase chain reaction primers targeting RB1 gene c.1075A
      demonstrated this same RB1 mutation. Conclusions and Relevance: In this study
      evaluating nucleic acids in the AH from Rb eyes undergoing salvage therapy with
      intravitreous injection of melphalan, the results suggest that the AH can serve
      as a surrogate tumor biopsy when Rb tumor tissue is not available. This novel
      method will allow for analyses of tumor-derived DNA in Rb eyes undergoing salvage
      therapy that have not been enucleated.

PMID- 29049478
TI  - Organ Donor Research: Overcoming Challenges, Increasing Opportunities.

PMID- 29049477
TI  - Association of the Addition of Oral Antibiotics to Mechanical Bowel Preparation
      for Left Colon and Rectal Cancer Resections With Reduction of Surgical Site
      Infections.
AB  - Importance: Surgical site infections (SSIs) after colorectal surgery remain a
      significant complication, particularly for patients with cancer, because they can
      delay the administration of adjuvant therapy. A combination of oral antibiotics
      and mechanical bowel preparation (MBP) is a potential, yet controversial, SSI
      prevention strategy. Objective: To determine the association of the addition of
      oral antibiotics to MBP with preventing SSIs in left colon and rectal cancer
      resections and its association with the timely administration of adjuvant
      therapy. Design, Setting, and Participants: A retrospective review was performed
      of 89 patients undergoing left colon and rectal cancer resections from October 1,
      2013, to December 31, 2016, at a single institution. A bowel regimen of oral
      antibiotics and MBP (neomycin sulfate, metronidazole hydrochloride, and magnesium
      citrate) was implemented August 1, 2015. Patients receiving MBP and oral
      antibiotics and those undergoing MBP without oral antibiotics were compared using
      univariate analysis. Multivariable logistic regression controlling for factors
      that may affect SSIs was used to evaluate the association between use of oral
      antibiotics and MBP and the occurrence of SSIs. Main Outcomes and Measures:
      Surgical site infections within 30 days of the index procedure and time to
      adjuvant therapy. Results: Of the 89 patients (5 women and 84 men; mean [SD] age,
      65.3 [9.2] years) in the study, 49 underwent surgery with MBP but without oral
      antibiotics and 40 underwent surgery with MBP and oral antibiotics. The patients
      who received oral antibiotics and MBP were younger than those who received only
      MBP (mean [SD] age, 62.6 [9.1] vs 67.5 [8.8] years; P = .01), but these 2 cohorts
      of patients were otherwise similar in baseline demographic, clinical, and cancer
      characteristics. Surgical approach (minimally invasive vs open) and case type
      were similarly distributed; however, the median operative time of patients who
      received oral antibiotics and MBP was longer than that of patients who received
      MBP only (391 minutes [interquartile range, 302-550 minutes] vs 348 minutes
      [interquartile range, 248-425 minutes]; P = .03). The overall SSI rate was lower
      for patients who received oral antibiotics and MBP than for patients who received
      MBP only (3 [8%] vs 13 [27%]; P = .03), with no deep or organ space SSIs or
      anastomotic leaks in patients who received oral antibiotics and MBP compared with
      9 organ space SSIs (18%; P = .004) and 5 anastomotic leaks (10%; P = .06) in
      patients who received MBP only. Despite this finding, there was no difference in
      median days to adjuvant therapy between the 2 cohorts (60 days [interquartile
      range, 46-73 days] for patients who received MBP only vs 72 days [interquartile
      range, 59-85 days] for patients who received oral antibiotics and MBP; P = .13).
      Oral antibiotics and MBP (odds ratio, 0.11; 95% CI, 0.02-0.86; P = .04) and
      minimally invasive surgery (odds ratio, 0.22; 95% CI, 0.05-0.89; P = .03) were
      independently associated with reduced odds of SSIs. Conclusions and Relevance:
      The combination of oral antibiotics and MBP is associated with a significant
      decrease in the rate of SSIs and should be considered for patients undergoing
      elective left colon and rectal cancer resections.

PMID- 29049479
TI  - Dual-Task Gait And Incident Dementia-A Step Forward, But Not There Yet-Reply.

PMID- 29049481
TI  - HSD3B1-A Predictive Biomarker in Advanced Prostate Cancer.

PMID- 29049480
TI  - Interpreting Biomarker Results in Individual Patients With Mild Cognitive
      Impairment in the Alzheimer's Biomarkers in Daily Practice (ABIDE) Project.
AB  - Importance: Biomarkers do not determine conversion to Alzheimer disease (AD)
      perfectly, and criteria do not specify how to take patient characteristics into
      account. Consequently, biomarker use may be challenging for clinicians,
      especially in patients with mild cognitive impairment (MCI). Objective: To
      construct biomarker-based prognostic models that enable determination of future
      AD dementia in patients with MCI. Design, Setting, and Participants: This study
      is part of the Alzheimer's Biomarkers in Daily Practice (ABIDE) project. A total
      of 525 patients with MCI from the Amsterdam Dementia Cohort (longitudinal cohort,
      tertiary referral center) were studied. All patients had their baseline visit to
      a memory clinic from September 1, 1997, through August 31, 2014. Prognostic
      models were constructed by Cox proportional hazards regression with patient
      characteristics (age, sex, and Mini-Mental State Examination [MMSE] score),
      magnetic resonance imaging (MRI) biomarkers (hippocampal volume, normalized whole
      brain volume), cerebrospinal fluid (CSF) biomarkers (amyloid-beta1-42, tau), and
      combined biomarkers. Data were analyzed from November 1, 2015, to October 1,
      2016. Main Outcomes and Measures: Clinical end points were AD dementia and any
      type of dementia after 1 and 3 years. Results: Of the 525 patients, 210 (40.0%)
      were female, and the mean (SD) age was 67.3 (8.4) years. On the basis of age,
      sex, and MMSE score only, the 3-year progression risk to AD dementia ranged from
      26% (95% CI, 19%-34%) in younger men with MMSE scores of 29 to 76% (95% CI, 65%
      84%) in older women with MMSE scores of 24 (1-year risk: 6% [95% CI, 4%-9%] to
      24% [95% CI, 18%-32%]). Three- and 1-year progression risks were 86% (95% CI, 71%
      95%) and 27% (95% CI, 17%-41%) when MRI results were abnormal, 82% (95% CI, 73%
      89%) and 26% (95% CI, 20%-33%) when CSF test results were abnormal, and 89% (95%
      CI, 79%-95%) and 26% (95% CI, 18%-36%) when the results of both tests were
      abnormal. Conversely, 3- and 1-year progression risks were 18% (95% CI, 13%-27%)
      and 3% (95% CI, 2%-5%) after normal MRI results, 6% (95% CI, 3%-9%) and 1% (95%
      CI, 0.5%-2%) after normal CSF test results, and 4% (95% CI, 2%-7%) and 0.5% (95%
      CI, 0.2%-1%) after combined normal MRI and CSF test results. The prognostic value
      of models determining any type of dementia were in the same order of magnitude
      although somewhat lower. External validation in Alzheimer's Disease Neuroimaging
      Initiative 2 showed that our models were highly robust. Conclusions and
      Relevance: This study provides biomarker-based prognostic models that may help
      determine AD dementia and any type of dementia in patients with MCI at the
      individual level. This finding supports clinical decision making and application
      of biomarkers in daily practice.

PMID- 29049483
TI  - Unnecessary Use of Inferior Vena Cava Filters: A Teachable Moment.

PMID- 29049484
TI  - A Strange Digital Tumor.

PMID- 29049482
TI  - A Test of the Transdiagnostic Dopamine Hypothesis of Psychosis Using Positron
      Emission Tomographic Imaging in Bipolar Affective Disorder and Schizophrenia.
AB  - Importance: The dopamine hypothesis suggests that dopamine abnormalities underlie
      psychosis, irrespective of diagnosis, implicating dopamine dysregulation in
      bipolar affective disorder and schizophrenia, in line with the research domain
      criteria approach. However, this hypothesis has not been directly examined in
      individuals diagnosed with bipolar disorder with psychosis. Objectives: To test
      whether dopamine synthesis capacity is elevated in bipolar disorder with
      psychosis and how this compares with schizophrenia and matched controls and to
      examine whether dopamine synthesis capacity is associated with psychotic symptom
      severity, irrespective of diagnostic class. Design, Setting, and Participants:
      This cross-sectional case-control positron emission tomographic study was
      performed in the setting of first-episode psychosis services in an inner-city
      area (London, England). Sixty individuals participated in the study (22 with
      bipolar psychosis [18 antipsychotic naive or free], 16 with schizophrenia [14
      antipsychotic naive or free], and 22 matched controls) and underwent
      fluorodihydroxyphenyl-l-alanine ([18F]-DOPA) positron emission tomography to
      examine dopamine synthesis capacity. Standardized clinical measures, including
      the Positive and Negative Syndrome Scale, Young Mania Rating Scale, and Global
      Assessment of Functioning, were administered. The study dates were March 2013 to
      November 2016. Main Outcomes and Measures: Dopamine synthesis capacity (Kicer)
      and clinical measures (Positive and Negative Syndrome Scale, Young Mania Rating
      Scale, and Global Assessment of Functioning). Results: The mean (SD) ages of
      participants were 23.6 (3.6) years in 22 individuals with bipolar psychosis (13
      male), 26.3 (4.4) years in 16 individuals with schizophrenia (14 male), and 24.5
      (4.5) years in controls (14 male). There was a significant group difference in
      striatal dopamine synthesis capacity (Kicer) (F2,57 = 6.80, P = .002). Kicer was
      significantly elevated in both the bipolar group (mean [SD], 13.18 [1.08] * 10-3
      min-1; P = .002) and the schizophrenia group (mean [SD], 12.94 [0.79] * 10-3 min
      1; P = .04) compared with controls (mean [SD], 12.16 [0.92] * 10-3 min-1). There
      was no significant difference in striatal Kicer between the bipolar and
      schizophrenia groups. Kicer was significantly positively correlated with positive
      psychotic symptom severity in the combined bipolar and schizophrenia sample
      experiencing a current psychotic episode, explaining 27% of the variance in
      symptom severity (n = 32, r = 0.52, P = .003). There was a significant positive
      association between Kicer and positive psychotic symptom severity in individuals
      with bipolar disorder experiencing a current psychotic episode (n = 16, r = 0.60,
      P = .01), which remained significant after adjusting for manic symptom severity.
      Conclusions and Relevance: These findings are consistent with a transdiagnostic
      role for dopamine dysfunction in the pathoetiology of psychosis and suggest
      dopamine synthesis capacity as a potential novel drug target for bipolar disorder
      and schizophrenia.

PMID- 29049485
TI  - Barber Knowledge and Recommendations Regarding Pseudofolliculitis Barbae and Acne
      Keloidalis Nuchae in an Urban Setting.

PMID- 29049486
TI  - Changes in Insurance Coverage Among Cancer Patients Under the Affordable Care
      Act.

PMID- 29049487
TI  - Poor Outcomes in Poor Patients?: Peripartum Cardiomyopathy-Not Just Black and
      White.

PMID- 29049488
TI  - Concentration of Potentially Preventable Spending Among High-Cost Medicare
      Subpopulations: An Observational Study.
AB  - Background: Little is known about whether potentially preventable spending is
      concentrated among a subset of high-cost Medicare beneficiaries. Objective: To
      determine the proportion of total spending that is potentially preventable across
      distinct subpopulations of high-cost Medicare beneficiaries. Design:
      Beneficiaries in the highest 10% of total standardized individual spending were
      defined as "high-cost" patients, using a 20% sample of Medicare fee-for-service
      claims from 2012. The following 6 subpopulations were defined using a claims
      based algorithm: nonelderly disabled, frail elderly, major complex chronic, minor
      complex chronic, simple chronic, and relatively healthy. Potentially preventable
      spending was calculated by summing costs for avoidable emergency department
      visits using the Billings algorithm plus inpatient and associated 30-day
      postacute costs for ambulatory care-sensitive conditions (ACSCs). The amount and
      proportion of potentially preventable spending were then compared across the high
      cost subpopulations and by individual ACSCs. Setting: Medicare. Participants: 6
      112 450 Medicare beneficiaries. Measurements: Proportion of spending deemed
      potentially preventable. Results: In 2012, 4.8% of Medicare spending was
      potentially preventable, of which 73.8% was incurred by high-cost patients.
      Despite making up only 4% of the Medicare population, high-cost frail elderly
      persons accounted for 43.9% of total potentially preventable spending ($6593 per
      person). High-cost nonelderly disabled persons accounted for 14.8% of potentially
      preventable spending ($3421 per person) and the major complex chronic group for
      11.2% ($3327 per person). Frail elderly persons accounted for most spending
      related to admissions for urinary tract infections, dehydration, heart failure,
      and bacterial pneumonia. Limitation: Potential misclassification in the
      identification of preventable spending and lack of detailed clinical data in
      administrative claims. Conclusion: Potentially preventable spending varied across
      Medicare subpopulations, with the majority concentrated among frail elderly
      persons. Primary Funding Source: The Commonwealth Fund.

PMID- 29049489
TI  - Possibilities Beyond Analyses of a Fee-for-Service Database and Clinician
      Mindset.

PMID- 29049490
TI  - Association of Rhinoplasty With Perceived Attractiveness, Success, and Overall
      Health.
AB  - Importance: To date, the impact of rhinoplasty surgery on social perceptions has
      not been quantified. Objective: To measure the association of rhinoplasty with
      observer-graded perceived attractiveness, success, and overall health. Design,
      Setting, and Participants: In a web-based survey, blinded casual observers viewed
      independent images of 13 unique patient faces before or after rhinoplasty. Delphi
      method was used to select standardized patient images, confirming appropriate
      patient candidacy and overall surgical effect. Observers rated the
      attractiveness, perceived success, and perceived overall health for each patient
      image. Facial perception questions were answered on a visual analog scale from 0
      to 100, where higher scores corresponded to more positive responses. A
      multivariate mixed-effects regression model was used to determine the effect of
      rhinoplasty while accounting for observer biases. To further characterize the
      effect of rhinoplasty, estimated ordinal rank change was calculated for each
      domain. Main Outcomes and Measures: The primary objective was to measure the
      effect of rhinoplasty on observer-graded perceived attractiveness, success, and
      overall health. Results: A total of 473 observers (mean age, 29 years [range, 18
      73 years]; 305 [70.8%] were female) successfully completed the survey. On
      multivariate regression, patients after rhinoplasty were rated as significantly
      more attractive (rhinoplasty effect, 6.26; 95% CI, 5.10-7.41), more successful
      (rhinoplasty effect, 3.24; 95% CI, 2.32-4.17), and overall healthier (rhinoplasty
      effect, 3.78; 95% CI, 2.79-4.81). The ordinal rank change for an average
      individual's perceived attractiveness, success, and overall health was a positive
      shift of 14, 9, and 10 out of 100 rank positions, respectively. Conclusions and
      Relevance: As perceived by casual observers, rhinoplasty surgery was
      associatedwith perceptions that in patients appeared significantly more
      attractive, more successful, and healthier. These results suggest patients
      undergoing rhinoplasty may derive a multifaceted benefit when partaking in social
      interactions. Furthermore, these results facilitate improved patient discussions
      aiming to provide more precise surgical expectations with an understanding that
      these results represent optimal outcomes. Level of Evidence: NA.

PMID- 29049491
TI  - Dermal Hyperneury and Multiple Sclerotic Fibromas in Multiple Endocrine Neoplasia
      Type 2A Syndrome.
AB  - Importance: Multiple endocrine neoplasia type 2 (MEN 2) syndrome is an autosomal
      dominant, hereditary cancer disorder caused by germline mutations in the RET
      (formerly MEN2A, MEN2B) proto-oncogene located on chromosomal band 10q11.21. Two
      distinct clinical forms have been described as the following phenotypes: multiple
      endocrine neoplasia type 2A (MEN 2A) and multiple endocrine neoplasia type 2B
      (MEN 2B) syndromes. The common and necessary nexus that defines these 2
      phenotypes is the presence of medullary thyroid carcinoma (MTC). The familial MTC
      type of MEN 2 syndrome was included within the spectrum of MEN 2A syndrome.
      Cutaneous manifestations of MEN 2A syndrome include macular amyloidosis, whereas
      MEN 2B syndrome is traditionally linked to multiple mucosal neuromas. Objectives:
      To describe a family with cutaneous manifestations not previously described in
      patients with MEN 2A syndrome and to discuss the association of this disorder
      with Cowden syndrome. Design, Setting, and Participants: Clinicopathologic
      correlation of cutaneous lesions and genetic studies in 11 members of a family
      with familial MTC. Interventions: Cutaneous lesions were histopathologically and
      immunohistochemically studied. Genetic screening for a germline mutation at the
      RET gene was performed in 11 family members. Main Outcomes and Measures:
      Identification of cutaneous lesions not previously described in patients with MEN
      2A syndrome. Results: This family of 11 individuals with familial MTC type of MEN
      2A syndrome demonstrated the moderate risk RET p.Val804Met (protein valine at
      residue 804 replaced by methionine) genetic mutation, with 2 of the relatives
      presenting with dermal hyperneury, cutaneous lesions classically described in MEN
      2B syndrome, and 1 relative also showing multiple sclerotic fibromas, a cutaneous
      manifestation of PTEN (phosphatase and tensin homologue) hamartoma-tumor
      syndrome. Conclusions and Relevance: Dermal hyperneury and multiple sclerotic
      fibromas should be added to the list of cutaneous manifestations of patients with
      the familial MTC type of MEN 2A syndrome.

PMID- 29049492
TI  - Association of HSD3B1 Genotype With Response to Androgen-Deprivation Therapy for
      Biochemical Recurrence After Radiotherapy for Localized Prostate Cancer.
AB  - Importance: The variant HSD3B1 (1245C) allele enhances dihydrotestosterone
      synthesis and predicts resistance to androgen-deprivation therapy (ADT) for
      biochemically recurrent prostate cancer after prostatectomy and for metastatic
      disease. Whether this is true after radiotherapy is unknown. Objective: To
      determine whether the HSD3B1 (1245C) allele predicts worse clinical outcomes from
      ADT for biochemical recurrence after radiotherapy. Design, Setting, and
      Participants: The Prostate Clinical Research Information System at Dana-Farber
      Cancer Institute was used to identify the study cohort, which included men
      treated with ADT for biochemical recurrence after primary radiotherapy between
      1996 and 2013. We retrospectively determined HSD3B1 genotype. Main Outcomes and
      Measures: Time to progression, time to metastasis, and overall survival according
      to genotype. Demographic and treatment characteristics were evaluated for
      confounders. Multivariable analyses were performed to adjust for known prognostic
      factors. Results: A total of 218 eligible men were identified, of whom 213 (98%)
      were successfully genotyped. Of these, 97 of 213 (46%), 96 of 213 (45%) and 20 of
      213 (9%) carried 0, 1, and 2 variant alleles. Overall variant allele frequency
      was 136 of 426 alleles (32%). Median patient age (interquartile range) was 69 (63
      74), 72 (65-78), and 69 (65-77) years for 0, 1, and 2 variant alleles (P = .03).
      Demographic and treatment factors were otherwise similar. During a median follow
      up of 7.9 years, median time to progression was 2.3 years (95% CI, 1.6-3.1 years)
      with 0 variant alleles, 2.3 years (95% CI, 1.5-3.3 years) with 1 variant allele,
      and 1.4 years (95% CI, 0.7-3.3 years) with 2 variant alleles (P = .68). Median
      time to metastasis diminished with the number of variant alleles inherited: 7.4
      (95% CI, 6.7-9.7), 5.8 (95% CI, 4.9-6.5), and 4.4 (95% CI, 3.0-5.7) years, with
      inheritance of 0, 1, and 2 variant alleles, respectively (P = .03). Median OS was
      7.7 (95% CI, 6.7-10.3), 6.9 (95% CI, 5.8-8.4), and 7.2 (95% CI, 3.8-7.9) years
      with inheritance of 0, 1, and 2 variant alleles, respectively (P = .31). On
      multivariable analysis with 0 variant alleles as the reference, the adjusted
      hazard ratio for metastasis was 1.19 (95% CI, 0.74-1.92) (P = .48) for 1 variant
      allele and 2.01 (95% CI, 1.02-3.97) (P = .045) for 2 variant alleles.
      Multivariable analysis did not demonstrate significant differences in TTP or OS.
      Conclusions and Relevance: In this study, the HSD3B1 (1245C) allele was
      associated with more rapid development of metastases in men treated with ADT for
      biochemical recurrence after primary radiation therapy for prostate cancer.
      Notably, 105 of 213 men (49%) had received prior ADT, and 119 of 213 (56%)
      received an androgen receptor antagonist during salvage treatment, both of which
      may attenuate the effect of the variant allele.

PMID- 29049494
TI  - Assessing Cosmetic Rhinoplasty Outcomes.

PMID- 29049495
TI  - Endogenous Endophthalmitis Associated With Intravenous Drug Use-Reply.

PMID- 29049493
TI  - Preliminary Evidence That Growth in Productive Language Differentiates Childhood
      Stuttering Persistence and Recovery.
AB  - Purpose: Childhood stuttering is common but is often outgrown. Children whose
      stuttering persists experience significant life impacts, calling for a better
      understanding of what factors may underlie eventual recovery. In previous
      research, language ability has been shown to differentiate children who stutter
      (CWS) from children who do not stutter, yet there is an active debate in the
      field regarding what, if any, language measures may mark eventual recovery versus
      persistence. In this study, we examined whether growth in productive language
      performance may better predict the probability of recovery compared to static
      profiles taken from a single time point. Method: Productive syntax and vocabulary
      diversity growth rates were calculated for 50 CWS using random coefficient
      models. Logistic regression models were then used to determine whether growth
      rates uniquely predict likelihood of recovery, as well as if these rates were
      predictive over and above currently identified correlates of stuttering onset and
      recovery. Results: Different linguistic profiles emerged between children who
      went on to recover versus those who persisted. Children who had steeper
      productive syntactic growth, but not vocabulary diversity growth, were more
      likely to recover by study end. Moreover, this effect held after controlling for
      initial language ability at study onset as well as demographic covariates.
      Conclusions: Results are discussed in terms of how growth estimates can be
      incorporated in recommendations for fostering productive language skills among
      CWS. The need for additional research on language in early stuttering and
      recovery is suggested.

PMID- 29049496
TI  - Fruit Juice and Fruit in the Special Supplemental Nutrition Program for Women,
      Infants, and Children Food Packages.

PMID- 29049497
TI  - Optimizing the Clinical Care of Lesbian, Gay, Bisexual, and Transgender Older
      Adults.

PMID- 29049498
TI  - A Review of Phonological Development of Mandarin-Speaking Children.
AB  - Purpose: Research into the phonological development of Chinese children is in its
      infancy compared with the relatively extensive data available on the English
      speaking population. This article provided a comprehensive review of empirical
      studies on the acquisition of Mandarin phonology. Method: Studies over the past
      45 years that describe phonological development in Mandarin-speaking children
      were located through electronic databases, citation searches, keyword searches
      through online search engines, and manual searches of libraries. The research
      design of the studies was reviewed, and findings of acceptable studies were
      summarized. Results: After reviewing the abstracts of 798 studies, a total of 12
      that met the inclusion criteria were retained. These studies are discussed with
      reference to the demographic background of participants, geographic regions,
      aspects of speech sounds measured, data collection tools, transcription systems
      used, reliability, and the main findings. Conclusions: The general developmental
      patterns reported were consistent. The methodological design varied
      substantially. These discrepancies, however, provide insights for further
      systematic investigations into phonological development in Mandarin.

PMID- 29049499
TI  - Leveraging Molecular Genetic Approaches to Yield Insights Into Major Depression
      Etiology and Clinical Presentation.

PMID- 29049500
TI  - Evidence-Based Guidelines to Eliminate Repetitive Laboratory Testing.
AB  - Routine daily laboratory testing of hospitalized patients reflects a wasteful
      clinical practice that threatens the value of health care. Choosing Wisely
      initiatives from numerous professional societies have identified repetitive
      laboratory testing in the face of clinical stability as low value care. Although
      laboratory expenditure often represents less than 5% of most hospital budgets,
      the impact is far-reaching given that laboratory tests influence nearly 60% to
      70% of all medical decisions. Excessive phlebotomy can lead to hospital-acquired
      anemia, increased costs, and unnecessary downstream testing and procedures.
      Efforts to reduce the frequency of laboratory orders can improve patient
      satisfaction and reduce cost without negatively affecting patient outcomes. To
      date, numerous interventions have been deployed across multiple institutions
      without a standardized approach. Health care professionals and administrative
      leaders should carefully strategize and optimize efforts to reduce daily
      laboratory testing. This review presents an evidence-based implementation
      blueprint to guide teams aimed at improving appropriate routine laboratory
      testing among hospitalized patients.

PMID- 29049501
TI  - Optical Coherence Tomography Angiography for Assessment of the 3-Dimensional
      Structures of Polypoidal Choroidal Vasculopathy.
AB  - Importance: Investigating the quantitative 3-dimensional (3-D) anatomy of
      polypoidal complex is important for a better understanding of the pathogenesis of
      polypoidal choroidal vasculopathy (PCV). Objective: To quantitatively evaluate
      the 3-D characteristics of polypoidal structures, branching vascular networks
      (BVNs), and origin of PCV using optical coherence tomography angiography (OCTA)
      and multiple image systems. Design, Setting, and Participants: A prospective,
      observational study was conducted in 47 consecutive Taiwanese patients (47 eyes)
      from May 21, 2015, to April 30, 2017. All participants were scanned with the
      Optovue-RTVue-XR-Avanti OCTA system. Patients in whom PCV was identified on OCTA
      were examined to define characteristics and structures of the original spouting
      vessels (stalks) from the choroid, polypoidal structures, and BVNs on OCTA. Main
      Outcomes and Measures: Quantitative analysis of 3-D structures of the polypoidal
      complex. Results: Among the 47 patients, the mean (SD) patient age was 68.9 (8.0)
      years, and 28 (59.6%) men were included. Clear images of polypoidal structures
      could be detected in 17 eyes (36.2%, 22 polypoidal structures), BVNs in 26 eyes
      (55.3%, 26 tufts of BVNs), and stalks of origin from the choroid in 26 eyes
      (55.3%, 26 stalks) on the en face plane on OCTA. All polypoidal structures were
      found at a mean (SD) height of 45.3 (36.1) MUm above the retinal pigment
      epithelium (RPE) reference plane that was preset by the machine, while the BVNs
      were found at a mean (SD) depth of 28.6 (14.2) MUm below the RPE reference plane
      and the choroidal stalks at 80.4 (24.4) MUm below RPE reference plane. The mean
      (SD) thickness of polypoidal structures was 38.4 (15.5) MUm and of BVNs, 60.2
      (25.0) MUm. The polypoidal structures were all above the Bruch membrane within
      the dome of the RPE detachment, the choroidal stalks were all in the choroid
      layer. The BVNs could be either above (up to 18 MUm), within, or below (up to 28
      MUm) the Bruch membrane and were in proximity to the double layers of flattened
      RPE detachment. Conclusions and Relevance: These results demonstrate a 3-D
      architecture of PCV that may be helpful for a better understanding of the
      anatomy, pathophysiology, and pathogenesis of PCV.

PMID- 29049503
TI  - Error in Figure.

PMID- 29049502
TI  - Benefits of Direct-Acting Antivirals for Hepatitis C.

PMID- 29049506
TI  - What You Can Do to Stop Firearm Violence.

PMID- 29049507
TI  - The Revised Declaration of Geneva: A Modern-Day Physician's Pledge.

PMID- 29049508
TI  - Outcomes in Women and Minorities Compared With White Men 1 Year After Everolimus
      Eluting Stent Implantation: Insights and Results From the PLATINUM Diversity and
      PROMUS Element Plus Post-Approval Study Pooled Analysis.
AB  - Importance: There exist limited outcomes data for women and minorities after
      contemporary percutaneous coronary intervention (PCI). Objective: To examine 1
      year outcomes in women and minorities vs white men after PCI with everolimus
      eluting stents. Design, Settings, and Participants: The PLATINUM Diversity study
      was a single-arm study enrolling women and minorities. Patient-level pooling with
      the PROMUS Element Plus Post-Approval Study was prespecified. Data on social
      determinants of health and language were collected in the PLATINUM Diversity
      cohort, which included 1501 patients at 52 US sites. The PROMUS Element Plus Post
      Approval study enrolled 2681 patients at 52 US sites with some site overlap and
      included an "all-comers" population. All patients were enrolled beginning in
      October 2014 and were followed for 12 months. Analyses began in August 2016.
      Interventions: Patients received 1 or more everolimus-eluting stent implantation.
      Main Outcomes and Measures: The primary end point was 1-year major adverse
      cardiac events (MACE), which included death/myocardial infarction (MI)/target
      vessel revascularization. Secondary ischemic end points were also evaluated.
      Results: The pooled study consisted of 4182 patients: 1635 white men (39.1%),
      1863 women (white and minority) (44.5%), and 1059 minority patients (women and
      men) (25.3%). Women and minorities had a higher prevalence of diabetes, prior
      stroke, hypertension, renal disease, and congestive heart failure than white men
      but lower rates of multivessel disease, prior coronary artery bypass graft
      surgery, prior MI, and smoking. Unadjusted 1-year MACE rates (white men, 7.6%;
      women, 8.6%; minorities, 9.6%) were similar between groups with no significant
      differences after risk adjustment. The adjusted risk of death/MI was higher among
      women (odds ratio, 1.6; 95% CI, 1.1-2.4) and minorities (odds ratio, 1.9; 95% CI,
      1.2-2.8) compared with white men and the adjusted risk of MI was higher in
      minorities (odds ratio, 2.6; 95% CI, 1.4-4.8). These differences were driven
      primarily by nonstent-related MIs. Within the PLATINUM Diversity cohort, the
      independent predictors of MACE were cardiogenic shock, renal disease, history of
      peripheral vascular disease, multivessel disease, widowhood, and lack of private
      insurance. Conclusions and Relevance: After contemporary everolimus-eluting stent
      implantation, women and minorities experience a similar risk of 1-year MACE but a
      higher adjusted risk of recurrent ischemic events primarily because of nonstent
      related MIs. Both clinical and angiographic factors and social determinants of
      health, including widowhood and insurance status, contribute to 1-year MACE among
      women and minorities.

PMID- 29049513
TI  - Contraceptive Coverage and the Balance Between Conscience and Access.

PMID- 29049509
TI  - Prenatal Air Pollution and Newborns' Predisposition to Accelerated Biological
      Aging.
AB  - Importance: Telomere length is a marker of biological aging that may provide a
      cellular memory of exposures to oxidative stress and inflammation. Telomere
      length at birth has been related to life expectancy. An association between
      prenatal air pollution exposure and telomere length at birth could provide new
      insights in the environmental influence on molecular longevity. Objective: To
      assess the association of prenatal exposure to particulate matter (PM) with
      newborn telomere length as reflected by cord blood and placental telomere length.
      Design, Setting, and Participants: In a prospective birth cohort (ENVIRONAGE
      [Environmental Influence on Ageing in Early Life]), a total of 730 mother-newborn
      pairs were recruited in Flanders, Belgium between February 2010 and December
      2014, all with a singleton full-term birth (>=37 weeks of gestation). For
      statistical analysis, participants with full data on both cord blood and
      placental telomere lengths were included, resulting in a final study sample size
      of 641. Exposures: Maternal residential PM2.5 (particles with an aerodynamic
      diameter <=2.5 MUm) exposure during pregnancy. Main Outcomes and Measures: In the
      newborns, cord blood and placental tissue relative telomere length were measured.
      Maternal residential PM2.5 exposure during pregnancy was estimated using a high
      resolution spatial-temporal interpolation method. In distributed lag models, both
      cord blood and placental telomere length were associated with average weekly
      exposures to PM2.5 during pregnancy, allowing the identification of critical
      sensitive exposure windows. Results: In 641 newborns, cord blood and placental
      telomere length were significantly and inversely associated with PM2.5 exposure
      during midgestation (weeks 12-25 for cord blood and weeks 15-27 for placenta). A
      5-ug/m3 increment in PM2.5 exposure during the entire pregnancy was associated
      with 8.8% (95% CI, -14.1% to -3.1%) shorter cord blood leukocyte telomeres and
      13.2% (95% CI, -19.3% to -6.7%) shorter placental telomere length. These
      associations were controlled for date of delivery, gestational age, maternal body
      mass index, maternal age, paternal age, newborn sex, newborn ethnicity, season of
      delivery, parity, maternal smoking status, maternal educational level, pregnancy
      complications, and ambient temperature. Conclusions and Relevance: Mothers who
      were exposed to higher levels of PM2.5 gave birth to newborns with shorter
      telomere length. The observed telomere loss in newborns by prenatal air pollution
      exposure indicates less buffer for postnatal influences of factors decreasing
      telomere length during life. Therefore, improvements in air quality may promote
      molecular longevity from birth onward.

PMID- 29049512
TI  - Time Requirements for Electronic Health Record Use in an Academic Ophthalmology
      Center.
AB  - Importance: Electronic health record (EHR) systems have transformed the practice
      of medicine. However, physicians have raised concerns that EHR time requirements
      have negatively affected their productivity. Meanwhile, evolving approaches
      toward physician reimbursement will require additional documentation to measure
      quality and cost of care. To date, little quantitative analysis has rigorously
      studied these topics. Objective: To examine ophthalmologist time requirements for
      EHR use. Design, Setting, and Participants: A single-center cohort study was
      conducted between September 1, 2013, and December 31, 2016, among 27 stable
      departmental ophthalmologists (defined as attending ophthalmologists who worked
      at the study institution for >=6 months before and after the study period).
      Ophthalmologists who did not have a standard clinical practice or who did not use
      the EHR were excluded. Exposures: Time stamps from the medical record and EHR
      audit log were analyzed to measure the length of time required by
      ophthalmologists for EHR use. Ophthalmologists underwent manual time-motion
      observation to measure the length of time spent directly with patients on the
      following 3 activities: EHR use, conversation, and examination. Main Outcomes and
      Measures: The study outcomes were time spent by ophthalmologists directly with
      patients on EHR use, conversation, and examination as well as total time required
      by ophthalmologists for EHR use. Results: Among the 27 ophthalmologists in this
      study (10 women and 17 men; mean [SD] age, 47.3 [10.7] years [median, 44; range,
      34-73 years]) the mean (SD) total ophthalmologist examination time was 11.2 (6.3)
      minutes per patient, of which 3.0 (1.8) minutes (27% of the examination time)
      were spent on EHR use, 4.7 (4.2) minutes (42%) on conversation, and 3.5 (2.3)
      minutes (31%) on examination. Mean (SD) total ophthalmologist time spent using
      the EHR was 10.8 (5.0) minutes per encounter (range, 5.8-28.6 minutes). The
      typical ophthalmologist spent 3.7 hours using the EHR for a full day of clinic:
      2.1 hours during examinations and 1.6 hours outside the clinic session. Linear
      mixed effects models showed a positive association between EHR use and billing
      level and a negative association between EHR use per encounter and clinic volume.
      Each additional encounter per clinic was associated with a decrease of 1.7
      minutes (95% CI, -4.3 to 1.0) of EHR use time per encounter for ophthalmologists
      with high mean billing levels (adjusted R2 = 0.42; P = .01). Conclusions and
      Relevance: Ophthalmologists have limited time with patients during office visits,
      and EHR use requires a substantial portion of that time. There is variability in
      EHR use patterns among ophthalmologists.

PMID- 29049514
TI  - A 52-Year-Old Man With Unheralded Syncope.

PMID- 29049515
TI  - Simulating Reversibility of Dense Core Vesicles Capture in En Passant Boutons:
      Using Mathematical Modeling to Understand the Fate of Dense Core Vesicles in En
      Passant Boutons.
AB  - The goal of this paper is to use mathematical modeling to investigate the fate of
      dense core vesicles (DCVs) captured in en passant boutons located in nerve
      terminals. One possibility is that all DCVs captured in boutons are destroyed,
      another possibility is that captured DCVs can escape and reenter the pool of
      transiting DCVs that move through the boutons, and a third possibility is that
      some DCVs are destroyed in boutons, while some reenter the transiting pool. We
      developed a model by applying the conservation of DCVs in various compartments
      composing the terminal, to predict different scenarios that emerge from the above
      assumptions about the fate of DCVs captured in boutons. We simulated DCV
      transport in type Ib and type III terminals. The simulations demonstrate that, if
      no DCV destruction in boutons is assumed and all captured DCVs reenter the
      transiting pool, the DCV fluxes evolve to a uniform circulation in a type Ib
      terminal at steady-state and the DCV flux remains constant from bouton to bouton.
      Because at steady-state the amount of captured DCVs is equal to the amount of
      DCVs that reenter the transiting pool, no decay of DCV fluxes occurs. In a type
      III terminal at steady-state, the anterograde DCV fluxes decay from bouton to
      bouton, while retrograde fluxes increase. This is explained by a larger capture
      efficiency of anterogradely moving DCVs than of retrogradely moving DCVs in type
      III boutons, while the captured DCVs that reenter the transiting pool are assumed
      to be equally split between anterogradely and retrogradely moving components. At
      steady-state, the physiologically reasonable assumption of no DCV destruction in
      boutons results in the same number of DCVs entering and leaving a nerve terminal.
      Because published experimental results indicate no DCV circulation in type III
      terminals, modeling results suggest that DCV transport in these type III
      terminals may not be at steady-state. To better understand the kinetics of DCV
      capture and release, future experiments in type III terminals at different times
      after DCV release (molting) may be proposed.

PMID- 29049516
TI  - Making a Case for Sanctuary Hospitals.

PMID- 29049517
TI  - "Job Lock" Among Long-term Survivors of Childhood Cancer: A Report From the
      Childhood Cancer Survivor Study.
AB  - Importance: Childhood cancer survivors may be reluctant to make changes in their
      employment because of access to health insurance. Objective: To examine the
      prevalence of "job lock" (staying at a job to keep work-related health insurance)
      in a sample drawn from an established, multi-institutional cohort of full-time
      employed childhood cancer survivors compared with a random sample of siblings and
      to explore factors associated with job lock among cancer survivors. Design,
      Setting, and Participants: Cross-sectional survey of full-time employed adult
      survivors of childhood cancer and a random sample of siblings derived from a
      cohort of 25 US pediatric oncology centers. Exposures: Data collection included
      sociodemographic factors, insurance coverage, chronic medical conditions, and
      treatment. Main Outcomes and Measures: Self-report of job lock and factors
      associated with job lock. Results: Among the 522 participants, 394 were cancer
      survivors (54.5% male) and 128 were siblings (51.5% male). Job lock was reported
      by 23.2% (95% CI, 18.9%-28.1%) of survivors, compared with 16.9% (95% CI, 11.1%
      25.0%) of siblings (P = .16). Job lock was more common among survivors reporting
      previous health insurance denial (relative risk [RR], 1.60; 95% CI, 1.03-2.52)
      and problems paying medical bills (RR, 2.43; 95% CI, 1.56-3.80). Among survivors,
      being female (RR, 1.70; 95% CI, 1.11-2.59; P = .01) and having a severe,
      disabling, or life-threatening health condition (RR, 1.72; 95% CI, 1.09-2.69; P =
      .02) were associated with job lock. Conclusions and Relevance: Job lock is common
      among long-term childhood cancer survivors who are employed full-time. A
      survivor's decision to remain employed at a job in order to maintain health
      insurance coverage may affect career trajectory, diminish potential earning
      power, and ultimately impact quality of life.

PMID- 29049518
TI  - Long-term Outcomes After Proton Beam Irradiation in Patients With Large Choroidal
      Melanomas.
AB  - Importance: Although radiotherapy has been used more frequently in past decades
      for the management of large melanomas, long-term efficacy of proton beam
      irradiation (PBI) of large choroidal melanomas has not been reported. Objective:
      To evaluate long-term outcomes in patients who underwent PBI for the treatment of
      large choroidal melanomas. Design, Setting, and Participants: Data were obtained
      at a single Boston, Massachusetts, academic tertiary referral practice for this
      retrospective cohort study. In total, 336 patients with large tumors treated over
      a 13-year period from January 1, 1985, to December 31, 1997, and followed up
      until the end points were reached or until December 31, 2008, were included. Data
      analyses were initially completed in February 2017 and finalized in July 2017.
      Large tumors were those with a height 10 mm or greater or a longest linear
      diameter greater than 16 mm or a height greater than 8 mm when the optic nerve
      was involved. Intervention: Proton beam irradiation (total 70 Gy) delivered in 5
      equal fractions. Main Outcomes and Measures: The primary outcomes of rates of
      visual acuity retention, eye retention, tumor recurrence, and melanoma-related
      mortality were calculated using Kaplan-Meier estimates, and Cox proportional
      hazards regression analyses were completed to evaluate risk factors for tumor
      recurrence and melanoma-related mortality. Results: In this cohort of 336
      patients with large tumors, 150 were women and 329 were white; mean (SD) age was
      60.0 (14.0) years. Of 178 patients without optic nerve involvement (tumor >1 disc
      diameter from optic nerve), the mean (SD) largest basal diameter was 18.1 (1.9)
      mm and mean height was 8.2 (2.7) mm. Optic nerve involvement and tumors greater
      than 8 mm were observed in 109 patients (32.4% of the cohort). Baseline visual
      acuity of 20/200 or better was observed in 244 patients (72.6%), and worse than
      20/800 in 52 (15.5%). Ten-year rates of visual acuity retention were 8.7% (95%
      CI, 4.1%-15.6%) for at least 20/200 and 22.4% (95% CI, 15.4%-30.4%) for at least
      counting fingers. Ten years after PBI therapy, the eye was retained (70.4%; 95%
      CI, 61.5%-77.6%) and tumor controlled (87.5%; 95% CI, 76.8%-93.5%) in most
      patients. The 10-year all-cause mortality rate was 60.7% (95% CI, 55.5%-65.9%).
      Approximately half of the patients died of metastatic uveal melanoma (10-year
      rate, 48.5%; 95% CI, 43.0%-54.4%). Conclusions and Relevance: This study
      demonstrates that eye conservation is possible in most cases, with ambulatory
      vision retained in a small proportion of patients 10 years after PBI. Tumor
      recurrence rates were low and mortality rates were comparable to those observed
      after enucleation.

PMID- 29049520
TI  - Oral Antibiotics for Colon Surgery: The Questions Remain the Same, as Do the
      Answers.

PMID- 29049519
TI  - Association of Bone Mineral Density With the Risk of Intracranial Aneurysm.
AB  - Importance: Disruption of extracellular matrix integrity is critically involved
      in both intracranial aneurysm and bone fragility. Furthermore, both intracranial
      aneurysm and osteoporosis have a female predominance, and sex hormones are
      considered to affect this discrepancy. Objective: To evaluate the association
      between bone mineral density and intracranial aneurysm. Design, Setting, and
      Participants: A cross-sectional study conducted with 14 328 patients who
      underwent brain magnetic resonance angiography and bone mineral densitometry as a
      part of a health examination at a specialized center for comprehensive health
      examination in Seoul, the largest metropolitan area in the Republic of Korea,
      between December 2004 and November 2015. After excluding patients with
      insufficient clinical information (n = 1102) and with ambiguous intracranial
      arterial lesion (n = 441), 12 785 were included in the analysis. Exposures: Bone
      mineral density was measured at the lumbar vertebrae (L1 to L4), femur neck, and
      total hip using dual-energy x-ray absorptiometry. Main Outcomes and Measures:
      Multiple logistic regression or linear regression was used to examine the
      association between tertiles of bone mineral density and the presence, size, and
      multiplicity of intracranial aneurysms. In secondary analyses, we analyzed
      postmenopausal women and men 50 years and older (n = 8722) because they are
      particularly at risk of decreased bone mineral density. Results: Among 12 785
      patients in the study (7242 women [56.6%]; mean [SD] age, 54.8 [10.1] years)
      intracranial aneurysms were found in 472 patients (3.7%). Lower bone mineral
      density was associated with an increased risk of harboring intracranial aneurysm.
      In multivariable logistic regression analyses, odds ratios for the highest
      compared with the lowest bone mineral density tertile were 1.30 (95% CI, 1.03
      1.64) in the lumbar spine, 1.30 (95% CI, 1.03-1.64) in the femoral neck, and 1.27
      (95% CI, 1.01-1.60) in the total hip after adjusting for age, sex, and vascular
      risk factors. In a linear regression model adjusted for age, sex, and vascular
      risk factors, the lowest tertile of bone mineral density in the lumbar spine was
      associated with an increased log-transformed size of aneurysm (beta, 0.196; SE,
      0.047). In secondary analyses, these associations were more definite and a low T
      score (<-1 SD) was additionally associated with multiple aneurysms (OR, 1.84; 95%
      CI, 1.05-3.30) after adjusting for age, sex, and vascular risk factors.
      Conclusions and Relevance: Bone mineral density may be associated with the
      presence, size, and multiplicity of intracranial aneurysm. The study findings
      provide evidence for shared pathophysiology between intracranial aneurysm and
      bone fragility.

PMID- 29049521
TI  - Can Measured Synergy Excitations Accurately Construct Unmeasured Muscle
      Excitations?
AB  - Accurate prediction of muscle and joint contact forces during human movement
      could improve treatment planning for disorders such as osteoarthritis, stroke,
      Parkinson's disease, and cerebral palsy. Recent studies suggest that muscle
      synergies, a low-dimensional representation of a large set of muscle
      electromyographic (EMG) signals (henceforth called "muscle excitations"), may
      reduce the redundancy of muscle excitation solutions predicted by optimization
      methods. This study explores the feasibility of using muscle synergy information
      extracted from eight muscle EMG signals (henceforth called "included" muscle
      excitations) to accurately construct muscle excitations from up to 16 additional
      EMG signals (henceforth called "excluded" muscle excitations). Using treadmill
      walking data collected at multiple speeds from two subjects (one healthy, one
      poststroke), we performed muscle synergy analysis on all possible subsets of
      eight included muscle excitations and evaluated how well the calculated time
      varying synergy excitations could construct the remaining excluded muscle
      excitations (henceforth called "synergy extrapolation"). We found that some, but
      not all, eight-muscle subsets yielded synergy excitations that achieved >90%
      extrapolation variance accounted for (VAF). Using the top 10% of subsets, we
      developed muscle selection heuristics to identify included muscle combinations
      whose synergy excitations achieved high extrapolation accuracy. For 3, 4, and 5
      synergies, these heuristics yielded extrapolation VAF values approximately 5%
      lower than corresponding reconstruction VAF values for each associated eight
      muscle subset. These results suggest that synergy excitations obtained from
      experimentally measured muscle excitations can accurately construct unmeasured
      muscle excitations, which could help limit muscle excitations predicted by muscle
      force optimizations.

PMID- 29049522
TI  - Ten Steps the Federal Government Should Take Now to Reverse the Opioid Addiction
      Epidemic.

PMID- 29049524
TI  - The 'entangled' stent: a preventable cause of paravalvular leak of the Perceval
      bioprosthesis.
AB  - Despite the excellent early performance of the Perceval sutureless valve, there
      have been recent reports of stent infolding, followed by paravalvular leak that
      was linked to valve oversizing. The purpose of this study was to review published
      reports by assessing photographic and radiological images. An in vitro study was
      also conducted with stent twisting that may occur during the collapse of the
      valve, termed 'stent entanglement', demonstrating consecutive successful valve
      collapse and implantation. This result has led us to hypothesize that infolding
      is due to a number of triggers, e.g. distortion of the stent overlooked during
      the final visual inspection of the implanted valve, rather than to excessive
      oversizing of the prosthesis as the sole cause, as repeatedly suggested in
      previous reports.

PMID- 29049525
TI  - Impact of the Haga Braincare Strategy on the burden of haemodynamic and embolic
      strokes related to cardiac surgery.
AB  - OBJECTIVES: This study prospectively evaluates the impact of the Haga Braincare
      Strategy (HBS) on the occurrence of haemodynamic and embolic stroke in a cohort
      of patients who underwent coronay artery bypass grafting (CABG), valve
      replacement of a combination of both types of surgery between 2012 and 2015 at
      the Haga Teaching Hospitals. METHODS: The HBS is a dual strategy based on a
      preoperative vascular work-up of the cerebral circulation by transcranial Doppler
      and a perioperative monitoring of the cerebral circulation by cerebral oximetry.
      Duplex of the carotid arteries and/or computed tomography angiography prior to
      surgery was performed in high-risk patients. Patients with severe carotid artery
      stenosis were scheduled for carotid angioplasty prior to surgery or waived from
      surgery. RESULTS: A total of 1065 patients were included. Poor cerebral
      haemodynamics were identified by transcranial Doppler in 2.1% of patients (n =
      22). Based on the HBS, 3 patients were waived from surgery, 4 received
      preoperative carotid angioplasty followed by cardiac surgery and the remaining
      patients were operated while being monitored with bilateral cerebral oximetry
      sensors. In all, 2.2% of the study group experienced a stroke (n = 23), of which
      none were classified as haemodynamic. Most of the remaining presumed embolic
      strokes showed a minor to moderate stroke severity. CONCLUSIONS: In this single
      centre prospective follow-up study, surveillance of cerebral perfusion by the HBS
      eliminated the occurrence of haemodynamic stroke while most of the residual
      strokes had a good to favourable prognosis.

PMID- 29049523
TI  - Oral Human Papillomavirus Infection: Differences in Prevalence Between Sexes and
      Concordance With Genital Human Papillomavirus Infection, NHANES 2011 to 2014.
AB  - Background: The burden of human papillomavirus (HPV)-positive oropharyngeal
      squamous cell carcinoma (OPSCC) is disproportionately high among men, yet
      empirical evidence regarding the difference in prevalence of oral HPV infection
      between men and women is limited. Concordance of oral and genital HPV infection
      among men is unknown. Objective: To determine the prevalence of oral HPV
      infection, as well as the concordance of oral and genital HPV infection, among
      U.S. men and women. Design: Nationally representative survey. Setting: Civilian
      noninstitutionalized population. Participants: Adults aged 18 to 69 years from
      NHANES (National Health and Nutrition Examination Survey), 2011 to 2014.
      Measurements: Oral rinse, penile swab, and vaginal swab specimens were evaluated
      by polymerase chain reaction followed by type-specific hybridization. Results:
      The overall prevalence of oral HPV infection was 11.5% (95% CI, 9.8% to 13.1%) in
      men and 3.2% (CI, 2.7% to 3.8%) in women (equating to 11 million men and 3.2
      million women nationwide). High-risk oral HPV infection was more prevalent among
      men (7.3% [CI, 6.0% to 8.6%]) than women (1.4% [CI, 1.0% to 1.8%]). Oral HPV 16
      was 6 times more common in men (1.8% [CI, 1.3% to 2.2%]) than women (0.3% [CI,
      0.1% to 0.5%]) (1.7 million men vs. 0.27 million women). Among men and women who
      reported having same-sex partners, the prevalence of high-risk HPV infection was
      12.7% (CI, 7.0% to 18.4%) and 3.6% (CI, 1.4% to 5.9%), respectively. Among men
      who reported having 2 or more same-sex oral sex partners, the prevalence of high
      risk HPV infection was 22.2% (CI, 9.6% to 34.8%). Oral HPV prevalence among men
      with concurrent genital HPV infection was 4-fold greater (19.3%) than among those
      without it (4.4%). Men had 5.4% (CI, 5.1% to 5.8%) greater predicted probability
      of high-risk oral HPV infection than women. The predicted probability of high
      risk oral HPV infection was greatest among black participants, those who smoked
      more than 20 cigarettes daily, current marijuana users, and those who reported 16
      or more lifetime vaginal or oral sex partners. Limitation: Sexual behaviors were
      self-reported. Conclusion: Oral HPV infection is common among U.S. men. This
      study's findings provide several policy implications to guide future OPSCC
      prevention efforts to combat this disease. Primary Funding Source: National
      Cancer Institute.

PMID- 29049526
TI  - Incorporating Patient and Caregiver Experiences Into Cardiovascular Clinical
      Trial Design.
AB  - Patient centeredness is a concept that is increasingly being viewed as essential
      for clinical research. A core principle involves a comprehensive assessment and
      integration of patient and caregiver perspectives into trial design. Importantly,
      this involves more than just soliciting feedback. Patients and caregivers are now
      considered vital members of the study team, even serving as coinvestigators who
      may help to conceive, plan, and develop the study; continue to direct the day-to
      day conduct of the study; and fully participate in the dissemination of the study
      results. The Patient-Centered Outcomes Research Institute offers substantial
      funding to support this approach, but getting started, particularly at
      institutions that lack a robust community engagement infrastructure, can be
      daunting. In this Special Communication, successful methods that have been used
      by researchers to engage patients, caregivers, and the broader health care
      community in the research process are outlined, and examples of currently funded
      studies that have fully engaged key stakeholders are described. Although trials
      are designed to assess efficacy and effectiveness and inform future
      implementation and dissemination, this Special Communication emphasizes methods
      to ensure trial results are relevant to and understood by the individuals and
      groups that they are intended to impact. Critical next steps in this new research
      approach are also discussed. In doing so, this will inspire future cardiovascular
      research that evaluates not only traditional end points, such as mortality and
      readmission, but also emphasizes true patient-centered outcomes, including
      quality of life, knowledge and satisfaction, caregiver burden, time tradeoffs,
      and out-of-pocket costs.

PMID- 29049527
TI  - Quadruple-valve infective endocarditis caused by Abiotrophia defectiva.
AB  - Quadruple-valve endocarditis is a challenging condition, for which there is
      limited treatment experience and poor overall survival. We report the first case
      caused by Abiotrophia defectiva that has been surgically treated both with the
      replacement of the aortic and pulmonary valves and the repair of the mitral and
      tricuspid valves with a good outcome. The patient's clinical course is described
      and a review of literature on this rare causative agent is given.

PMID- 29049528
TI  - An aorto-oesophageal fistula treated with endovascular aortic repair: the fate of
      untreated oesophageal lesion on endoscopic follow-up.
AB  - Oesophageal foreign body is an emergency situation. Once oesophageal perforation
      occurs, damage and subsequent infection involving surrounding tissue or organs
      may ensue. We present here a rare case of aorto-oesophageal fistula which was
      treated with challenges. An old lady with fishbone induced oesophageal
      perforation, aortic pseudoaneurysm and mediastinal haematoma was treated with
      great vessel stent-graft placed in aortic arch, and the fish bone was removed
      under endoscopy thereafter. During the early follow-up period, part of the graft
      stent was discovered in the oesophageal perforation with no haemorrhage. The
      patient is still in good condition during follow-up.

PMID- 29049529
TI  - A novel method for prevention of stent graft-induced distal re-dissection after
      thoracic endovascular aortic repair for Type B aortic dissection.
AB  - OBJECTIVES: Stent graft-induced distal re-dissection (SIDR) is a burdensome
      complication after thoracic endovascular aortic repair (TEVAR) for Type B aortic
      dissection. We developed a novel method to prevent SIDR by placing a small
      diameter short stent graft [Excluder Aortic Extender (Cuff)] at the distal
      landing zone (DLZ) and reviewed its effectiveness in this study. METHODS: Ninety
      patients who underwent TEVAR for Type B aortic dissection using commercially
      available devices between January 2008 and September 2016 were retrospectively
      reviewed. Among them, TEVAR with the Cuff technique was performed in 36 (40%)
      cases, in which a Cuff was placed at the DLZ in the descending aorta prior to the
      main stent graft deployment to avoid excessive stent graft oversizing at the
      distal end. The effectiveness of the Cuff technique was assessed by evaluating
      mid-term clinical results, including the incidence of SIDR. RESULTS: Technical
      success was achieved in all 90 cases. During a median follow-up time of 40.4
      months (range 0.2-90.6 months), 8 SIDRs were documented using multidetector
      computed tomography images. Freedom from SIDR was significantly lower in the Cuff
      group (Cuff: 100%/5 years vs non-Cuff: 84.6%/5 years; P = 0.04), whereas no
      difference was observed between both groups in the oversizing rate at the DLZ
      (19.9 +/- 8.5% vs 17.8 +/- 9.9%; P = 0.29). CONCLUSIONS: Placement of a small
      diameter short stent graft at the DLZ (Cuff technique) in TEVAR for aortic
      dissection is an easy procedure that may reduce the incidence of SIDR.

PMID- 29049531
TI  - Human Epidermal Growth Factor Receptor 2 as a Molecular Biomarker for Metastatic
      Colorectal Cancer.

PMID- 29049530
TI  - Risk of Venous Thromboembolism Among Otolaryngology Patients vs General Surgery
      and Plastic Surgery Patients.
AB  - Importance: Venous thromboembolism (VTE), which includes deep venous thrombosis
      or pulmonary embolism, is the number 1 cause of preventable death in surgical
      patients. Current guidelines from the American College of Chest Physicians
      provide VTE prevention recommendations that are specific to individual surgical
      subspecialties; however, no guidelines exist for otolaryngology. Objective: To
      examine the rate of VTE for various otolaryngology procedures compared with an
      established average-risk field (general surgery) and low-risk field (plastic
      surgery). Design, Setting, and Participants: This cohort study compared the rate
      of VTE after different otolaryngology procedures with those of general and
      plastic surgery in the American College of Surgeons National Surgical Quality
      Improvement Program from January 1, 2005, through December 31, 2013. We used
      univariate and multivariable logistic regression analysis of clinical
      characteristics, cancer status, and Caprini score to compare different risk
      stratification of patients. Data analysis was performed from May 1, 2016, to
      April 1, 2017. Exposures: Surgery. Main Outcomes and Measures: Thirty-day rate of
      VTE. Results: A total of 1 295 291 patients, including 31 896 otolaryngology
      patients (mean [SD] age, 53.9 [16.7] years; 14 260 [44.7%] male; 21 603 [67.7%]
      white), 27 280 plastic surgery patients (mean [SD] age, 50.5 [13.9] years; 4835
      [17.7%] male; 17 983 [65.9%] white), and 1 236 115 general surgery patients (mean
      [SD] age, 54.9 [17.2] years; 484 985 [39.2%] male; 867 913 [70.2%] white) were
      compared. The overall 30-day rate of VTE was 0.5% for otolaryngology compared
      with 0.7% for plastic surgery and 1.2% for general surgery. We identified a high
      risk group for VTE in otolaryngology (n = 3625) that included free or regional
      tissue transfer, laryngectomy, composite resection, skull base surgery, and
      incision and drainage. High-risk otolaryngology patients experienced similar
      rates of VTE as general surgery patients across all Caprini risk levels. Low-risk
      otolaryngology patients (n = 28 271) experienced lower rates of VTE than plastic
      surgery patients across all Caprini risk levels. Malignant tumors were associated
      with VTE; however, the rates varied by cancer type and were 11-fold greater for
      cancers of the upper aerodigestive tract compared with thyroid cancers (odds
      ratio, 10.97; 95% CI,7.38-16.31). Venous thromboembolism was associated with a 14
      fold higher 30-day mortality among otolaryngology patients (5.1% mortality with
      VTE vs 0.4% mortality without VTE; difference, 4.7%; 95% CI of the difference,
      2.2%-9.3%). Conclusions and Relevance: Most patients undergoing otolaryngology
      procedures are at low risk of VTE, indicating that guidelines for a low-risk
      population could be adapted to otolaryngology. Patients undergoing high-risk
      otolaryngology procedures should be considered as candidates for more aggressive
      VTE prophylaxis.

PMID- 29049532
TI  - Pulmonary valve restitution following transannular patch repair of tetralogy of
      Fallot.
AB  - Chronic pulmonary insufficiency following transannular patch repair of tetralogy
      of Fallot may mandate restoration of a competent pulmonary valve. Pulmonary valve
      leaflets that are preserved at initial surgery may grow and develop normal
      morphology and subsequent valve repair may be possible. We reviewed our
      experience with native pulmonary valve restitution following transannular patch
      repair (2001-15). The cohort included 9 patients with a median age of 18.7 (range
      10.6-31.3) years. Operative technique involved reapproximation of the anterior
      commissure of the pulmonary valve. Median length of stay was 3 days, and there
      were no deaths. At median follow-up of 2.0 (0.4-13.5) years, pulmonary
      insufficiency was graded as <=mild (n = 4), mild-moderate or moderate (n = 4) and
      moderate-severe (n = 1); pulmonary stenosis was <=mild (n = 8) and moderate (n =
      1), with median peak gradient of 21 (16-64) mmHg. No patient required
      reintervention. At reoperation to treat pulmonary insufficiency in repaired TOF,
      if residual leaflets are found with favourable anatomy, restitution of the native
      valve should be considered. This valve-preserving technique avoids the certain
      failure of a bioprosthesis and is associated with favourable early outcomes. The
      viability of this option may influence surgeons to leave the pulmonary leaflets
      in situ at the time of initial repair.

PMID- 29049533
TI  - Association of Antidepressant Medications With Incident Type 2 Diabetes Among
      Medicaid-Insured Youths.
AB  - Importance: Antidepressants are one of the most commonly prescribed classes of
      psychotropic medications among US youths. For adults, there is emerging evidence
      on the increased risk of type 2 diabetes in association with antidepressant use.
      However, little is known about the antidepressant treatment-emergent risk of type
      2 diabetes among youths. Objective: To assess the association between
      antidepressant use and the risk of incident type 2 diabetes in youths by
      antidepressant subclass and according to duration of use, cumulative dose, and
      average daily dose. Design, Setting, and Participants: A retrospective cohort
      study was conducted using Medicaid claims data from 4 geographically diverse,
      large states of youths 5 to 20 years of age who initiated antidepressant
      treatment from January 1, 2005, to December 31, 2009. Exposures: Antidepressant
      use (selective serotonin reuptake inhibitors [SSRIs] or serotonin-norepinephrine
      reuptake inhibitors [SNRIs], tricyclic or other cyclic antidepressants, and other
      antidepressants) was assessed using the following 4 time-varying measures:
      current or former use, duration of use, cumulative dose, and average daily dose.
      Main Outcomes and Measures: Incident type 2 diabetes was assessed using discrete
      time failure models, adjusting for disease risk score estimated using more than
      125 baseline and time-dependent covariates. Results: In this cohort of 119 608
      youths aged 5 to 20 years who initiated antidepressant treatment (59 087 female
      youths and 60 521 male youths; 54.7% between 5 and 14 years of age) with a mean
      follow-up of 22.8 months, 79 285 [66.3%] had SSRI or SNRI exposure. The risk of
      type 2 diabetes was significantly greater during current use than former use of
      SSRIs or SNRIs (absolute risk, 1.29 per 10 000 person-months vs 0.64 per 10 000
      person-months; adjusted relative risk [RR], 1.88; 95% CI, 1.34-2.64) and
      tricyclic or other cyclic antidepressants (absolute risk, 0.89 per 10 000 person
      months vs 0.48 per 10 000 person-months; RR, 2.15; 95% CI, 1.06-4.36), but not of
      other antidepressants (absolute risk, 1.15 per 10 000 person-months vs 1.12 per
      10 000 person-months; RR, 0.99; 95% CI, 0.66-1.50). Furthermore, for youths
      currently using SSRIs or SNRIs, the risk of type 2 diabetes increased with the
      duration of use (RR, 2.66; 95% CI, 1.45-4.88 for >210 days and RR, 2.56; 95% CI,
      1.29-5.08 for 151-210 days compared with 1-90 days) and with the cumulative dose
      (RR, 2.44; 95% CI, 1.35-4.43 for >4500 mg and RR, 2.17; 95% CI, 1.07-4.40 for
      3001-4500 mg compared with 1-1500 mg in fluoxetine hydrochloride dose
      equivalents). By contrast, neither the duration nor the cumulative dose of other
      antidepressants was associated with an increased risk of type 2 diabetes. The
      risk of type 2 diabetes increased significantly with the average daily dose among
      youths with more than 150 days of SSRI or SNRI use (RR, 2.39; 95% CI, 1.04-5.52
      for >15.0 vs <=15.0 mg/d) but not among youths with 1 to 150 days of SSRI or SNRI
      use. Conclusions and Relevance: In a large cohort of youths insured by Medicaid,
      the use of SSRIs or SNRIs-the most commonly used antidepressant subclass-was
      associated with an increased risk of type 2 diabetes that intensified with
      increasing duration of use, cumulative dose, and average daily dose.

PMID- 29049535
TI  - All Thiopurines Are Equal but Some Thiopurines Are More Equal Than Others.

PMID- 29049534
TI  - High-frequency percussive ventilation in cardiac surgery patients failing
      mechanical conventional ventilation.
AB  - OBJECTIVES: Failure of mechanical conventional ventilation (MCV) after cardiac
      surgery portends a dismal prognosis, with extracorporeal membrane oxygenation
      frequently utilized as a salvage therapy. We describe our experience with high
      frequency percussive ventilation (HFPV) as a rescue therapy for hypoxaemia
      refractory to MCV after cardiac surgery. METHODS: In a 6-year retrospective
      analysis from 2009 to 2015, we identified 16 subjects who required HFPV after
      cardiac surgery. Data regarding demographics, intraoperative details,
      postoperative ventilatory settings including length of time on HFPV and
      postoperative outcomes were collected. The primary outcome was improvement in
      oxygenation as measured by pre- and post-HFPV partial pressures of oxygen (pO2)
      and ratio of pO2 to fraction of inspired oxygen (P/F ratio). RESULTS: Sixteen
      patients required HFPV after cardiac surgery. Operative procedures included
      coronary artery bypass surgery (n = 6), aortic aneurysm or dissection repair (n =
      5), valve with bypass surgery (n = 2), aortic valve replacement (n = 2) and
      extracorporeal membrane oxygenation (n = 1). Median pO2 increased from 61 to
      149.5 mmHg (P < 0.001) and the median P/F ratio improved from 62 to 169 (P <
      0.001). The improvement in pO2 and P/F ratio was durable at 24 h whether the
      patient was returned to MCV (n = 4) or remained on HFPV (n = 12) with pO2 and P/F
      ratio increasing from 61 to 104 mmHg (P < 0.001) and from 62 to 193.5 (P <
      0.001), respectively. Survival to discharge was 81%. CONCLUSIONS: In our cohort
      of cardiac surgical patients, HFPV was successfully utilized as a rescue therapy,
      obviating the need for extracorporeal membrane oxygenation. Although further
      studies are warranted, HFPV should be considered in cardiac surgical patients
      failing MCV.

PMID- 29049536
TI  - Preoperative SYNTAX score to assess the late outcomes after coronary
      endarterectomy for the diffusely diseased left anterior descending artery.
AB  - OBJECTIVES: To evaluate whether the preoperative Synergy between Percutaneous
      Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) score was
      associated with late outcomes of coronary endarterectomy (CE) for the diffusely
      diseased left anterior descending artery (LAD). METHODS: We retrospectively
      analysed 205 of 212 patients undergoing CE for the diffusely diseased LAD between
      September 2004 and May 2016, excluding 2 patients without preoperative
      angiographic data and 5 redo cases. The mean SYNTAX score was 34.6. Patients were
      divided into 3 groups according to their SYNTAX score: low (<=22, n = 26),
      intermediate (23-32, n = 58) and high (>=33, n = 121). The study end-points were
      cardiac death and major adverse cardiac and cerebrovascular events, defined as
      all-cause death, cerebrovascular accidents, non-fatal myocardial infarction and
      repeat revascularization. All CEs involved long arteriotomy and the
      reconstruction of the endarterectomized LAD using the skeletonized internal
      thoracic artery. RESULTS: Postoperative mortality and morbidity were similar
      between the groups. The median follow-up period was 5.4 years. We found no
      significant difference in the cumulative cardiac death-free survival rate at 5
      years (91.1% vs 100% vs 98.3%; log-rank, P = 0.196) or major adverse cardiac and
      cerebrovascular events (61.6% vs 71.5% vs 76.7%; log-rank, P = 0.258) in the low,
      intermediate and high SYNTAX score groups, respectively. Univariate and
      multivariate Cox proportional hazard analyses revealed no significant association
      between the study end-points and individual components of the SYNTAX score for
      the LAD. CONCLUSIONS: The preoperative SYNTAX score and its individual components
      for the LAD were not associated with late outcomes following CE for the diffusely
      diseased LAD.

PMID- 29049537
TI  - Bilateral bidirectional Glenn: outcome of off-pump technique.
AB  - OBJECTIVES: Off-pump bilateral bidirectional Glenn (b-BDG) poses a surgical
      challenge and may add complexity to the postoperative outcome especially
      regarding uniformity of the anastomosis and central pulmonary artery growth.
      Herein, we report early- and mid-term outcomes after off-pump b-BDG without using
      superior vena cava decompression techniques. METHODS: Ninety-seven consecutive
      patients, between 2009 and 2014, were included in this prospective study. All
      patients had complete pre- and postoperative clinical and detailed neurological
      assessments. Diagnosis and follow-up were done by echocardiography and cardiac
      catheterization for assessment of pulmonary artery anatomically and
      haemodynamically. Median follow-up period was 3.5 years. Perioperative variables,
      clinical outcome, morbidity, mortality and follow-up data were recorded. RESULTS:
      Hypoplastic right ventricle was present in 52 cases (53.6%) and hypoplastic left
      ventricle was present in 45 cases (46.4%). Mean superior vena cava pressure on
      clamping was 21.49 +/- 3.04 mmHg. Mean total clamping time was 23.11 +/- 3.44
      min. Mean oxygen saturation increased from preoperative 69.22 +/- 6.01% to 83.66
      +/- 3.97% after b-BDG construction (P-value <= 0.0001). The Nakata index
      increased from 288.47 +/- 28.66 mm2/m2 to 303.64 +/- 26.85mm2/m2 on follow-up (P
      value <= 0.05). In-hospital mortality was 4 patients (4.1%) due to low-cardiac
      output. There were chylothorax in 9 patients (9.3%) and convulsions in 4 patients
      (4.1%) who were treated conservatively. CONCLUSIONS: Off-pump b-BDG can be
      conducted safely, with a uniform anastomosis that allows a good central pulmonary
      artery growth for subsequent Fontan completion. Moreover, avoiding the use of
      cardiopulmonary bypass is more economic and less hazardous.

PMID- 29049538
TI  - 3D printed mitral valve models: affordable simulation for robotic mitral valve
      repair.
AB  - OBJECTIVES: 3D printed mitral valve (MV) models that capture the suture response
      of real tissue may be utilized as surgical training tools. Leveraging clinical
      imaging modalities, 3D computerized modelling and 3D printing technology to
      produce affordable models complements currently available virtual simulators and
      paves the way for patient- and pathology-specific preoperative rehearsal.
      METHODS: We used polyvinyl alcohol, a dissolvable thermoplastic, to 3D print
      moulds that were casted with liquid platinum-cure silicone yielding flexible, low
      cost MV models capable of simulating valvular tissue. Silicone-moulded MV models
      were fabricated for 2 morphologies: the normal MV and the P2 flail. The moulded
      valves were plication and suture tested in a laparoscopic trainer box with a da
      Vinci Si robotic surgical system. One cardiothoracic surgery fellow and 1
      attending surgeon qualitatively evaluated the ability of the valves to
      recapitulate tissue feel through surveys utilizing the 5-point Likert-type scale
      to grade impressions of the valves. RESULTS: Valves produced with the moulding
      and casting method maintained anatomical dimensions within 3% of directly 3D
      printed acrylonitrile butadiene styrene controls for both morphologies. Likert
      type scale mean scores corresponded with a realistic material response to sutures
      (5.0/5), tensile strength that is similar to real MV tissue (5.0/5) and
      anatomical appearance resembling real MVs (5.0/5), indicating that evaluators
      'agreed' that these aspects of the model were appropriate for training.
      Evaluators 'somewhat agreed' that the overall model durability was appropriate
      for training (4.0/5) due to the mounting design. Qualitative differences in
      repair quality were notable between fellow and attending surgeon. CONCLUSIONS: 3D
      computer-aided design, 3D printing and fabrication techniques can be applied to
      fabricate affordable, high-quality educational models for technical training that
      are capable of differentiating proficiency levels among users.

PMID- 29049539
TI  - Mid- and Long-Term Outcome Comparisons of Everolimus-Eluting Bioresorbable
      Scaffolds Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta
      analysis.
AB  - Background: Percutaneous coronary interventions to implant bioresorbable vascular
      scaffolds (BVSs) were designed to reduce the late thrombotic events that occur
      with metallic stents. Purpose: To estimate the incidence of scaffold thrombosis
      after BVS implantation and compare everolimus-eluting BVSs with everolimus
      eluting metallic stents (EESs) in terms of safety and efficacy at mid- and long
      term follow-up in adults who had a percutaneous coronary intervention. Data
      Sources: PubMed, EMBASE, the Cochrane Library, conference proceedings, and
      relevant Web sites from inception until 20 May 2017, without language
      restriction. Study Selection: 7 randomized trials and 38 observational studies
      (each with a minimum of 6 months and 100 patient-years of follow-up) in adults
      with coronary artery disease who had a BVS or an EES and reported scaffold or
      stent thrombosis (main outcome) or other secondary outcomes (such as death,
      myocardial infarction, or revascularization). Data Extraction: 2 reviewers
      independently extracted study data, rated study quality, and assessed strength of
      evidence. Data Synthesis: The pooled incidence of definite or probable scaffold
      thrombosis after BVS implantation was 1.8% (95% CI, 1.5% to 2.2%) at a median
      follow-up of 1 year (41 studies, 21 884 patients) and 0.8% (CI, 0.5% to 1.3%)
      beyond 1 year (14 studies, 4688 patients). Seven trials involving 5578 patients
      that directly compared BVSs with EESs showed an increased risk for definite or
      probable scaffold thrombosis (odds ratio [OR], 3.40 [CI, 2.01 to 5.76]) with BVSs
      at a median follow-up of 25 months. Increased risks were present at early
      (prominently subacute), late, and very late stages, and odds beyond 1 year were
      almost double those seen within 1 year. Bioresorbably vascular scaffolds
      increased risks for myocardial infarction (OR, 1.63 [CI, 1.26 to 2.10]), target
      lesion revascularization (OR, 1.31 [CI, 1.03 to 1.67]), and target lesion failure
      (OR, 1.37 [CI, 1.12 to 1.66]); the odds for these 3 end points also increased
      over time. The incidences of all-cause, cardiac, and noncardiac death and of
      target vessel and any revascularization did not differ. Limitation: Quality of
      observational studies was unclear, and some data were unpublished. Conclusion:
      Compared with EESs, BVSs increased the risks for scaffold thrombosis and other
      thrombotic events at mid- and long-term follow-up, and risks increased over time.
      Primary Funding Source: National Natural Science Foundation of China.

PMID- 29049540
TI  - Feasibility, Process, and Outcomes of Cardiovascular Clinical Trial Data Sharing:
      A Reproduction Analysis of the SMART-AF Trial.
AB  - Importance: Data sharing is as an expanding initiative for enhancing trust in the
      clinical research enterprise. Objective: To evaluate the feasibility, process,
      and outcomes of a reproduction analysis of the THERMOCOOL SMARTTOUCH Catheter for
      the Treatment of Symptomatic Paroxysmal Atrial Fibrillation (SMART-AF) trial
      using shared clinical trial data. Design, Setting, and Participants: A
      reproduction analysis of the SMART-AF trial was performed using the data sets,
      data dictionary, case report file, and statistical analysis plan from the
      original trial accessed through the Yale Open Data Access Project using the SAS
      Clinical Trials Data Transparency platform. SMART-AF was a multicenter, single
      arm trial evaluating the effectiveness and safety of an irrigated, contact force
      sensing catheter for ablation of drug refractory, symptomatic paroxysmal atrial
      fibrillation in 172 participants recruited from 21 sites between June 2011 and
      December 2011. Analysis of the data was conducted between December 2016 and April
      2017. Main Outcomes and Measures: Effectiveness outcomes included freedom from
      atrial arrhythmias after ablation and proportion of participants without any
      arrhythmia recurrence over the 12 months of follow-up after a 3-month blanking
      period. Safety outcomes included major adverse device- or procedure-related
      events. Results: The SMART AF trial participants' mean age was 58.7 (10.8) years,
      and 72% were men. The time from initial proposal submission to final analysis was
      11 months. Freedom from atrial arrhythmias at 12 months postprocedure was similar
      compared with the primary study report (74.0%; 95% CI, 66.0-82.0 vs 76.4%; 95%
      CI, 68.7-84.1). The reproduction analysis success rate was higher than the
      primary study report (65.8%; 95% CI 56.5-74.2 vs 75.6%; 95% CI, 67.2-82.5).
      Adverse events were minimal and similar between the 2 analyses, but contact force
      range or regression models could not be reproduced. Conclusions and Relevance:
      The feasibility of a reproduction analysis of the SMART-AF trial was demonstrated
      through an academic data-sharing platform. Data sharing can be facilitated
      through incentivizing collaboration, sharing statistical code, and creating more
      decentralized data sharing platforms with fewer restrictions to data access.

PMID- 29049541
TI  - Industry Influence in Dermatology Clinical Practice Guideline Development.

PMID- 29049542
TI  - Nanoparticle Optimization for Enhanced Targeted Anticancer Drug Delivery.
AB  - Nanoparticle (NP)-based drug delivery is a promising method to increase the
      therapeutic index of anticancer agents with low median toxic dose. The delivery
      efficiency, corresponding to the fraction of the injected NPs that adhere to the
      tumor site, depends on NP size a and aspect ratio AR. Values for these variables
      are currently chosen empirically, which may not result in optimal targeted drug
      delivery. This study applies rigorous optimization to the design of NPs. A
      preliminary investigation revealed that delivery efficiency increases
      monotonically with a and AR. However, maximizing a and AR results in nonuniform
      drug distribution, which impairs tumor regression. Therefore, a multiobjective
      optimization (MO) problem is formulated to quantify the trade-off between NPs
      accumulation and distribution. The MO is solved using the derivative-free mesh
      adaptive direct search algorithm. Theoretically, the Pareto-optimal set consists
      of an infinite number of mathematically equivalent solutions to the MO problem.
      However, interesting design solutions can be identified subjectively, e.g., the
      ellipsoid with a major axis of 720 nm and an aspect ratio of 7.45, as the
      solution closest to the utopia point. The MO problem formulation is then extended
      to optimize NP biochemical properties: ligand-receptor binding affinity and
      ligand density. Optimizing physical and chemical properties simultaneously
      results in optimal designs with reduced NP sizes and thus enhanced cellular
      uptake. The presented study provides an insight into NP structures that have
      potential for producing desirable drug delivery.

PMID- 29049543
TI  - Isolated transfusion of leucocyte-depleted apheresis platelet concentrates and
      outcomes after cardiac surgery.
AB  - We investigated the association of isolated leucocyte-depleted single-donor
      apheresis platelet concentrate transfusion with short- and long-term outcomes of
      patients undergoing isolated or combined coronary artery bypass and valve
      surgery. Propensity score matching was used to compare the results of patients
      without blood product transfusion and patients with isolated platelet transfusion
      (n = 167 per group). The primary end-point was a composite of operative
      complications. Additionally, we assessed coronary reintervention and overall
      mortality over a follow-up period of 7.5 years. In the platelet- and platelet+
      groups, the composite end-point was reached at 9.6% and 12.3%, respectively (P =
      0.307). None of the patients died within 30 days. None of the patients needed
      coronary reintervention during follow-up. Long-term mortality was similar between
      groups (P > 0.05). Isolated leucocyte-depleted apheresis platelet transfusion
      does not appear to be associated with an increase in morbidity or mortality in
      non-complex cardiac surgery. However, larger studies are needed.

PMID- 29049544
TI  - Incorrect Author Affiliation.

PMID- 29049545
TI  - Contributions of Kinetic Energy and Viscous Dissipation to Airway Resistance in
      Pulmonary Inspiratory and Expiratory Airflows in Successive Symmetric Airway
      Models With Various Bifurcation Angles.
AB  - The aim of this study was to investigate and quantify contributions of kinetic
      energy and viscous dissipation to airway resistance during inspiration and
      expiration at various flow rates in airway models of different bifurcation
      angles. We employed symmetric airway models up to the 20th generation with the
      following five different bifurcation angles at a tracheal flow rate of 20 L/min:
      15 deg, 25 deg, 35 deg, 45 deg, and 55 deg. Thus, a total of ten computational
      fluid dynamics (CFD) simulations for both inspiration and expiration were
      conducted. Furthermore, we performed additional four simulations with tracheal
      flow rate values of 10 and 40 L/min for a bifurcation angle of 35 deg to study
      the effect of flow rate on inspiration and expiration. Using an energy balance
      equation, we quantified contributions of the pressure drop associated with
      kinetic energy and viscous dissipation. Kinetic energy was found to be a key
      variable that explained the differences in airway resistance on inspiration and
      expiration. The total pressure drop and airway resistance were larger during
      expiration than inspiration, whereas wall shear stress and viscous dissipation
      were larger during inspiration than expiration. The dimensional analysis
      demonstrated that the coefficients of kinetic energy and viscous dissipation were
      strongly correlated with generation number. In addition, the viscous dissipation
      coefficient was significantly correlated with bifurcation angle and tracheal flow
      rate. We performed multiple linear regressions to determine the coefficients of
      kinetic energy and viscous dissipation, which could be utilized to better
      estimate the pressure drop in broader ranges of successive bifurcation
      structures.

PMID- 29049546
TI  - A unique variation with five branches of the aortic arch.
AB  - Here, we present a unique case with 5 branches of the aortic arch (AA), namely
      the right common carotid artery, left common carotid artery, left thyrocervical
      trunk, left subclavian artery and right subclavian artery (RSA), from right to
      left. We found that the left thyrocervical trunk originated directly from the AA
      rather than the left subclavian artery. In addition, the RSA arose dorsally as
      the last branch of the AA and passed posteriorly to the oesophagus to supply the
      right upper limb. In addition, the right vertebral artery originated from the
      right common carotid artery instead of the RSA. Despite numerous studies on AA
      variations, to our knowledge, this is the first case of the left thyrocervical
      trunk originating directly from the AA and the RSA arising dorsally as the last
      branch of a 5-branch AA. Our case provides useful information to anatomists,
      radiologists and neck and thoracic surgeons.

PMID- 29049547
TI  - Management of Stage I Squamous Cell Carcinoma of the Anal Canal.

PMID- 29049548
TI  - Multimodal Analgesia in Outpatient Head and Neck Surgery: A Feasibility and
      Safety Study.

PMID- 29049549
TI  - Transapical cardioscopic mitral annuloplasty: a short-term survival study in a
      porcine model.
AB  - OBJECTIVES: The transapical approach provides concurrent surgical access to the
      mitral and the aortic valves, the root of the aorta and the left atrium. We
      previously showed the feasibility of transapical cardioscopic (TAC) surgery in a
      non-survival porcine model. However, reproducibility and feasibility of ring
      implantation using TAC have not been reported. Therefore, in this study, we
      hypothesized that implantation of a mitral annuloplasty ring can be feasibly and
      safely carried out endoscopically via the apex of the heart. METHODS: Using a
      porcine model in a short-term survival study, TAC mitral annuloplasty was
      performed in 6 pigs via an incision over the xyphoid, under cardiopulmonary
      bypass and cardiac arrest. A mitral annuloplasty ring was implanted via the apex
      to a normal mitral annulus, using a customized set of instruments and techniques.
      Haemodynamics, echocardiography, cardiac computed tomography, ventriculography,
      electrocardiography and histopathology studies were used to evaluate the function
      of the mitral valve and the left ventricle, coronary system and conduction system
      in the perioperative period and 4 weeks later. RESULTS: All 6 animals survived
      and recovered from the TAC annuloplasty procedure. Postimplantation examination
      showed that the mitral valve was competent, left ventricular ejection fraction
      was 63 +/- 4%, left ventricular length was 6.2 +/- 0.5 cm and left ventricular
      end-diastolic volume was 80 +/- 10 ml, which were comparable to preoperative
      values. Apart from a dense scar at the apex, no significant injury was noticed on
      the ventricle, the chordae and the mitral leaflets. The bypass, cross-clamp and
      implantation times were 181 +/- 55 min, 130 +/- 37 min and 47 +/- 6 min,
      respectively. CONCLUSIONS: Despite long surgical times due to the initial
      learning curve, successful execution of mitral ring annuloplasty could be safely
      achieved using the TAC approach, via a small incision without the involvement of
      sternum or the right pleural cavity, thereby potentially expanding the indication
      to patients with high-risk full sternotomy or right thoracotomy.

PMID- 29049550
TI  - Mid-term outcomes of congenital mitral valve surgery: Shone's syndrome is a risk
      factor for death and reintervention.
AB  - OBJECTIVES: To study the recent trends and outcomes of congenital mitral valve
      surgery in children. METHODS: From 2008 to 2014, 84 procedures in 66 consecutive
      patients (41 procedures in 31 patients with mitral stenosis and 43 procedures in
      35 patients with mitral regurgitation) were retrospectively evaluated. The mean
      age at surgery was 4.3 +/- 5.4 years, and 27 patients (41%) were neonates or
      infants. RESULTS: Seven (11%) patients died during the follow-up period of 3.2 +/
      2.3 years and 5 (71%) were <1 year. Ten mitral valve replacements were performed
      in 8 patients, including 1 pulmonary valve homograft, 3 Contegra conduits of 12
      mm thickness in the intra-annular position and 6 mechanical valves. Shone's
      syndrome, dysplastic valve, a need for valve replacement and age <1 year were the
      risk factors for death or reoperation in a univariable analysis, while in a
      multivariable analysis of all patients, valve replacement and age <1 year
      remained as risk factors. In a multivariable analysis of 27 patients aged <1
      year, mitral valve dysplasia was a significant risk factor for reoperation or
      death. The 5-year rate of freedom from death or reoperation in neonates or
      infants was 55% and that in patients aged >1 year was 88% (P = 0.003).
      CONCLUSIONS: An age of <1 year, mitral valve dysplasia and a need for mitral
      valve replacement were associated with a higher incidence of death or
      reoperation. Primary mitral valve replacement or univentricular strategy may have
      to be considered for symptomatic neonates with Shone's syndrome.

PMID- 29049551
TI  - History of Lymphoma.

PMID- 29049552
TI  - Addressing Population Health: Integrators in the Accountable Health Communities
      Model.

PMID- 29049553
TI  - Evaluating Industry Payments Among Dermatology Clinical Practice Guidelines
      Authors.
AB  - Importance: It is well documented that financial conflicts of interest influence
      medical research and clinical practice. Prior to the Open Payments provisions of
      the Affordable Care Act, financial ties became apparent only through self
      disclosure. The nature of financial interests has not been studied among
      physicians who develop dermatology clinical practice guidelines. Objective: To
      evaluate payments received by physicians who author dermatology clinical practice
      guidelines, compare disclosure statements for accuracy, determine whether
      pharmaceutical companies from which the authors received payments manufactured
      products related to the guidelines, and examine the extent to which the American
      Academy of Dermatology enforced their Administrative Regulations for guideline
      development. Design, Setting, and Participants: Three American Academy of
      Dermatology guidelines published from 2013 to 2016 were retrieved. Double data
      extraction was used to record financial payments received by 49 guideline authors
      using the Open Payments database. Payments received by the authors from the date
      of the initial literature search to the date of publication were used to evaluate
      disclosure statement accuracy, detail the companies providing payments, and
      evaluate Administrative Regulations enforcement. This study is applicable to
      clinical practice guideline panels drafting recommendations, physicians using
      clinical practice guidelines to inform patient care, and those establishing
      policies for guideline development. Main Outcomes and Measures: Our main outcomes
      are the monetary values and types of payments received by physicians who author
      dermatology guidelines and the accuracy of disclosure statements. Data were
      collected from the Open Payments database and analyzed descriptively. Results: Of
      the 49 authors evaluated, 40 received at least 1 reported industry payment, 31
      accepted more than $1000, 25 accepted more than $10 000, and 18 accepted more
      than $50 000. Financial payments amounted to a mean of $157 177 per author. The
      total reimbursement among the 49 authors from 2013 to 2015 was $7 701 681. Of the
      40 authors receiving payments, 22 did not accurately disclose industry
      relationships. Authors received payments from companies with products directly
      related to the guideline topic. Violations to the Administrative Regulations were
      found. Conclusions and Relevance: Dermatology clinical practice guideline authors
      received sizable industry payments and did not completely disclose these
      payments. The American Academy of Dermatology policies may benefit from stricter
      enforcement or the adoption of new standards.

PMID- 29049556
TI  - Identified.

PMID- 29049557
TI  - Dysmorphophobia and the Wolf Man.

PMID- 29049558
TI  - From Paris to Vienna-The Varied Names and Descriptions of Cutaneous Lupus
      Erythematosus in the 19th Century.

PMID- 29049559
TI  - Linking Dermatology, Neurology, and Psychiatry-Interdisciplinary Contributions of
      Ian Bruce Sneddon.

PMID- 29049560
TI  - Moon Dust.

PMID- 29049561
TI  - Cleopatra and Sour Milk-The Ancient Practice of Chemical Peeling.

PMID- 29049563
TI  - Red cell distribution width is a prognostic marker of perioperative stroke in
      patients undergoing cardiac valve surgery.
AB  - OBJECTIVES: Numerous studies have shown that elevated red cell distribution width
      (RDW) is associated with poor outcomes in patients with cardiovascular diseases
      such as coronary artery disease, peripheral artery disease or stroke. The
      usefulness of the RDW as a predictor of perioperative stroke in patients with
      valve disease undergoing valve surgery is currently unknown. The aim of the study
      was to evaluate the prognostic value of RDW for stroke in the early postoperative
      period in patients undergoing valve replacement or repair surgery. METHODS: A
      prospective study was conducted on a group of 500 consecutive patients with
      haemodynamically significant valvular heart disease who underwent elective
      valvular surgery. Preoperative complete blood count, data on risk factors, the
      course of operations and the postoperative period were assessed. The primary end
      point at the 30-day follow-up was perioperative stroke or transient ischaemic
      attack. The secondary end-point was death from all causes in patients with
      perioperative stroke. Univariate analysis, followed by multivariate regression
      analysis, was performed. RESULTS: The perioperative stroke occurred in 14
      patients. At multivariate analysis: RDW [odds ratio (OR) 1.640, 95% confidence
      interval (CI) 1.132-2.377; P = 0.009] and haemoglobin (OR 0.655, 95% CI 0.447
      0.961; P = 0.03) remained independent predictors of the primary end-point.
      Receiver operator characteristics analysis determined a cut-off value of RDW for
      the prediction of the occurrence of the perioperative stroke/transient ischaemic
      attack at 14.1%. Creatinine (OR 1.015, 95% CI 1.004-1.026; P = 0.0079) and RDW
      (OR 1.493, 95% CI 1.171-1.815; P = 0.04) were associated with an increased risk
      of death in patients with perioperative stroke. CONCLUSIONS: Elevated RDW is
      associated with a higher risk of perioperative stroke/transient ischaemic attack
      and death in patients with perioperative stroke.

PMID- 29049554
TI  - Genetic Association of Major Depression With Atypical Features and Obesity
      Related Immunometabolic Dysregulations.
AB  - Importance: The association between major depressive disorder (MDD) and obesity
      may stem from shared immunometabolic mechanisms particularly evident in MDD with
      atypical features, characterized by increased appetite and/or weight (A/W) during
      an active episode. Objective: To determine whether subgroups of patients with MDD
      stratified according to the A/W criterion had a different degree of genetic
      overlap with obesity-related traits (body mass index [BMI] and levels of C
      reactive protein [CRP] and leptin). Design, Setting, and Patients: This
      multicenter study assembled genome-wide genotypic and phenotypic measures from 14
      data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case
      control, cohort, and population-based studies, including 26 628 participants with
      established psychiatric diagnoses and genome-wide genotype data. Data on BMI were
      available for 15 237 participants. Data were retrieved and analyzed from
      September 28, 2015, through May 20, 2017. Main Outcomes and Measures: Lifetime
      DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with
      MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms
      as decreased or increased. Results: Data included 11 837 participants with MDD
      and 14 791 control individuals, for a total of 26 628 participants (59.1% female
      and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the
      decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic
      variants explained approximately 10% of the heritability in the 2 subgroups. The
      increased A/W subgroup showed a strong and positive genetic correlation (SE) with
      BMI (0.53 [0.15]; P = 6.3 * 10-4), whereas the decreased A/W subgroup showed an
      inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W
      subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18;
      95% CI, 1.12-1.25; P = 1.6 * 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02
      1.13; P = 7.3 * 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 * 10-3).
      Conclusions and Relevance: The phenotypic associations between atypical
      depressive symptoms and obesity-related traits may arise from shared
      pathophysiologic mechanisms in patients with MDD. Development of treatments
      effectively targeting immunometabolic dysregulations may benefit patients with
      depression and obesity, both syndromes with important disability.

PMID- 29049564
TI  - A new technique to implant a transcatheter inflatable, fully repositionable
      prosthesis in aortic stenosis with severe asymmetric calcification.
AB  - OBJECTIVES: In contrast to stented transcatheter aortic valves, the Direct Flow
      Medical (DFM) valve is a stentless bovine aortic bioprosthesis mounted in a non
      metallic inflatable frame. Hence, severe asymmetric annular calcification may
      result in residually elevated transaortic pressure gradients after DFM
      implantation. We present a novel intraprocedural dilatation (IDIL) technique for
      successful implantation of the DFM valve in the presence of complex annular
      calcification. METHODS: Between January 2014 and May 2015, 55 patients underwent
      DFM valve-based transcatheter aortic valve implantation at our institution. Of
      these, 5 patients required an IDIL technique due to a residual intraoperative
      transaortic pressure mean gradient above 15 mmHg. The mean patient age was 73 +/-
      8.2 years; the mean logistic EuroSCORE was 24.5 +/- 8.2% and the mean Society of
      Thoracic Surgeons score was 6.3 +/- 4.3%. RESULTS: The IDIL technique immediately
      attenuated transvalvular mean pressure gradients from 20 +/- 2 mmHg to 6 +/- 1
      mmHg. The results remained stable during the 30-day observation period at 10 +/-
      3 mmHg. Minimal paravalvular aortic regurgitation (trace) was detected in 2
      patients. No in-hospital deaths were observed. CONCLUSIONS: The IDIL technique
      facilitates safe DFM valve implantation in patients with complex asymmetric
      annular calcification without adverse side effects on valve structure or
      performance in short-term follow-up.

PMID- 29049565
TI  - A low-cost bioprosthetic semilunar valve for research, disease modelling and
      surgical training applications.
AB  - OBJECTIVES: This paper provides detailed instructions for constructing low-cost
      bioprosthetic semilunar valves for animal research and clinical training. This
      work fills an important gap between existing simulator training valves and
      clinical valves by providing fully functioning designs that can be employed in ex
      vivo and in vivo experiments and can also be modified to model valvular disease.
      METHODS: Valves are constructed in 4 steps consisting of creating a metal frame,
      covering it with fabric and attaching a suture ring and leaflets. Computer-aided
      design files are provided for making the frame from wire or by metal 3D printing.
      The covering fabric and suturing ring are made from materials readily available
      in a surgical lab, while the leaflets are made from pericardium. The entire
      fabrication process is described in figures and in a video. To demonstrate
      disease modelling, design modifications are described for producing paravalvular
      leaks, and these valves were evaluated in porcine ex vivo (n = 3) and in vivo (n
      = 6) experiments. RESULTS: Porcine ex vivo and acute in vivo experiments
      demonstrate that the valves can replicate the performance of clinical valves for
      research and training purposes. Surgical implantation is similar, and
      echocardiograms are comparable to clinical valves. Furthermore, valve leaflet
      function was satisfactory during acute in vivo tests with little central
      regurgitation, while the paravalvular leak modifications consistently produced
      leaks in the desired locations. CONCLUSIONS: The detailed design procedure
      presented here, which includes a tutorial video and computer-aided design files,
      should be of substantial benefit to researchers developing valve disease models
      and to clinicians developing realistic valve training systems.

PMID- 29049566
TI  - Evaluation of patients who underwent resympathectomy for treatment of primary
      hyperhidrosis.
AB  - OBJECTIVES: Video thoracoscopic sympathectomy is the recommended surgical
      treatment for primary hyperhidrosis and has a high success rate. Despite this
      high success rate, some patients are unresponsive and eventually need a
      resympathectomy. Few studies have previously analysed exclusively the results of
      these resympathectomies in patients with primary hyperhidrosis. None of the
      studies have objectively evaluated the degree of response to surgery or the
      improvement in quality of life after resympathectomies. METHODS: This is a
      retrospective study, evaluating 15 patients from an initial group of 2300
      patients who underwent resympathectomy after failure of the primary surgical
      treatment. We evaluated sympathectomy levels of resection, technical
      difficulties, surgical complications preoperative quality of life, response to
      treatment and quality-of-life improvement 30 days after each surgery. RESULTS:
      Regarding gender, 11 (73.3%) patients were women. The average age was 23.2 with
      SD of 5.17 years, and the mean body mass index was 20.9 (SD 2.12). Ten patients
      had major complaints about their hands (66%) and 5 (33%) patients about their
      forearms. A high degree of response to sympathectomy occurred in 73% of patients.
      In 11 of these patients, the improvement in quality of life was considered high,
      3 showed a mild improvement and 1 did not improve. No major complications
      occurred; the presence of adhesions was reported in 11 patients and pleural
      drainage was necessary in 4 patients. CONCLUSIONS: Resympathectomy is an
      effective procedure, and it improves the quality of life in patients with primary
      hyperhidrosis who failed after the first surgery.

PMID- 29049568
TI  - Skin-like Wearable Health Monitors.

PMID- 29049567
TI  - Black Women in Medicine-A Documentary.

PMID- 29049569
TI  - Rapid Test for Antibiotic Susceptibility.

PMID- 29049570
TI  - A Retinal Scan for Alzheimer Disease.

PMID- 29049571
TI  - Using Antimullerian Hormone to Predict Fertility.

PMID- 29049572
TI  - Gatekeeping Strategies for Avoiding False-Positive Results in Clinical Trials
      With Many Comparisons.

PMID- 29049573
TI  - Management of a Diabetic Foot.

PMID- 29049575
TI  - Science and the Trump Administration.

PMID- 29049576
TI  - Medicolegal: Illegal Prescribing of Intoxicating Liquor.

PMID- 29049577
TI  - Effects of Behavioral Interventions on Inappropriate Antibiotic Prescribing in
      Primary Care 12 Months After Stopping Interventions.

PMID- 29049578
TI  - The FAST Examination for Children With Abdominal Trauma.

PMID- 29049579
TI  - Security of Text Messaging in Clinical Care.

PMID- 29049580
TI  - Elevated Brain Amyloid in Cognitively Normal Individuals.

PMID- 29049581
TI  - The FAST Examination for Children With Abdominal Trauma-Reply.

PMID- 29049582
TI  - Elevated Brain Amyloid in Cognitively Normal Individuals-Reply.

PMID- 29049583
TI  - Security of Text Messaging in Clinical Care-Reply.

PMID- 29049584
TI  - Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe
      Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and
      Young Adults With Type 1 Diabetes.
AB  - Importance: Insulin pump therapy may improve metabolic control in young patients
      with type 1 diabetes, but the association with short-term diabetes complications
      is unclear. Objective: To determine whether rates of severe hypoglycemia and
      diabetic ketoacidosis are lower with insulin pump therapy compared with insulin
      injection therapy in children, adolescents, and young adults with type 1
      diabetes. Design, Setting, and Participants: Population-based cohort study
      conducted between January 2011 and December 2015 in 446 diabetes centers
      participating in the Diabetes Prospective Follow-up Initiative in Germany,
      Austria, and Luxembourg. Patients with type 1 diabetes younger than 20 years and
      diabetes duration of more than 1 year were identified. Propensity score matching
      and inverse probability of treatment weighting analyses with age, sex, diabetes
      duration, migration background (defined as place of birth outside of Germany or
      Austria), body mass index, and glycated hemoglobin as covariates were used to
      account for relevant confounders. Exposures: Type 1 diabetes treated with insulin
      pump therapy or with multiple (>=4) daily insulin injections. Main Outcomes and
      Measures: Primary outcomes were rates of severe hypoglycemia and diabetic
      ketoacidosis during the most recent treatment year. Secondary outcomes included
      glycated hemoglobin levels, insulin dose, and body mass index. Results: Of 30 579
      patients (mean age, 14.1 years [SD, 4.0]; 53% male), 14 119 used pump therapy
      (median duration, 3.7 years) and 16 460 used insulin injections (median duration,
      3.6 years). Patients using pump therapy (n = 9814) were matched with 9814
      patients using injection therapy. Pump therapy, compared with injection therapy,
      was associated with lower rates of severe hypoglycemia (9.55 vs 13.97 per 100
      patient-years; difference, -4.42 [95% CI, -6.15 to -2.69]; P < .001) and diabetic
      ketoacidosis (3.64 vs 4.26 per 100 patient-years; difference, -0.63 [95% CI, 
      1.24 to -0.02]; P = .04). Glycated hemoglobin levels were lower with pump therapy
      than with injection therapy (8.04% vs 8.22%; difference, -0.18 [95% CI, -0.22 to 
      0.13], P < .001). Total daily insulin doses were lower for pump therapy compared
      with injection therapy (0.84 U/kg vs 0.98 U/kg; difference, -0.14 [-0.15 to 
      0.13], P < .001). There was no significant difference in body mass index between
      both treatment regimens. Similar results were obtained after propensity score
      inverse probability of treatment weighting analyses in the entire cohort.
      Conclusions and Relevance: Among young patients with type 1 diabetes, insulin
      pump therapy, compared with insulin injection therapy, was associated with lower
      risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic
      control during the most recent year of therapy. These findings provide evidence
      for improved clinical outcomes associated with insulin pump therapy compared with
      injection therapy in children, adolescents, and young adults with type 1
      diabetes.

PMID- 29049586
TI  - Rhinoplasty.

PMID- 29049585
TI  - Association Between Biomarkers of Ovarian Reserve and Infertility Among Older
      Women of Reproductive Age.
AB  - Importance: Despite lack of evidence of their utility, biomarkers of ovarian
      reserve are being promoted as potential markers of reproductive potential.
      Objective: To determine the associations between biomarkers of ovarian reserve
      and reproductive potential among women of late reproductive age. Design, Setting,
      and Participants: Prospective time-to-pregnancy cohort study (2008 to date of
      last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a
      history of infertility who had been trying to conceive for 3 months or less,
      recruited from the community in the Raleigh-Durham, North Carolina, area.
      Exposures: Early-follicular-phase serum level of antimullerian hormone (AMH),
      follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. Main
      Outcomes and Measures: The primary outcomes were the cumulative probability of
      conception by 6 and 12 cycles of attempt and relative fecundability (probability
      of conception in a given menstrual cycle). Conception was defined as a positive
      pregnancy test result. Results: A total of 750 women (mean age, 33.3 [SD, 3.2]
      years; 77% white; 36% overweight or obese) provided a blood and urine sample and
      were included in the analysis. After adjusting for age, body mass index, race,
      current smoking status, and recent hormonal contraceptive use, women with low AMH
      values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted
      probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared
      with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of
      attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women
      with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly
      different predicted probability of conceiving after 6 cycles of attempt (63%; 95%
      CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%
      66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%
      78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine
      [n = 69]) did not have a significantly different predicted probability of
      conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women
      (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt
      (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels
      (n = 737) were not associated with the probability of conceiving in a given cycle
      (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and
      Relevance: Among women aged 30 to 44 years without a history of infertility who
      had been trying to conceive for 3 months or less, biomarkers indicating
      diminished ovarian reserve compared with normal ovarian reserve were not
      associated with reduced fertility. These findings do not support the use of
      urinary or blood follicle-stimulating hormone tests or antimullerian hormone
      levels to assess natural fertility for women with these characteristics.

PMID- 29049588
TI  - Global Health: What's in It for Us?

PMID- 29049590
TI  - Discrimination and Calibration of Clinical Prediction Models: Users' Guides to
      the Medical Literature.
AB  - Accurate information regarding prognosis is fundamental to optimal clinical care.
      The best approach to assess patient prognosis relies on prediction models that
      simultaneously consider a number of prognostic factors and provide an estimate of
      patients' absolute risk of an event. Such prediction models should be
      characterized by adequately discriminating between patients who will have an
      event and those who will not and by adequate calibration ensuring accurate
      prediction of absolute risk. This Users' Guide will help clinicians understand
      the available metrics for assessing discrimination, calibration, and the relative
      performance of different prediction models. This article complements existing
      Users' Guides that address the development and validation of prediction models.
      Together, these guides will help clinicians to make optimal use of existing
      prediction models.

PMID- 29049591
TI  - As Heroin Death Rates Rose, So Did Illicit Drug Seizures.

PMID- 29049592
TI  - Virgin Islands' Zika Awareness.

PMID- 29049593
TI  - Spatiotopic updating of visual feature information.
AB  - Saccades shift the retina with high-speed motion. In order to compensate for the
      sudden displacement, the visuomotor system needs to combine saccade-related
      information and visual metrics. Many neurons in oculomotor but also in visual
      areas shift their receptive field shortly before the execution of a saccade
      (Duhamel, Colby, & Goldberg, 1992; Nakamura & Colby, 2002). These shifts
      supposedly enable the binding of information from before and after the saccade.
      It is a matter of current debate whether these shifts are merely location based
      (i.e., involve remapping of abstract spatial coordinates) or also comprise
      information about visual features. We have recently presented fMRI evidence for a
      feature-based remapping mechanism in visual areas V3, V4, and VO (Zimmermann,
      Weidner, Abdollahi, & Fink, 2016). In particular, we found fMRI adaptation in
      cortical regions representing a stimulus' retinotopic as well as its spatiotopic
      position. Here, we asked whether spatiotopic adaptation exists independently from
      retinotopic adaptation and which type of information is behaviorally more
      relevant after saccade execution. We first adapted at the saccade target location
      only and found a spatiotopic tilt aftereffect. Then, we simultaneously adapted
      both the fixation and the saccade target location but with opposite tilt
      orientations. As a result, adaptation from the fixation location was carried
      retinotopically to the saccade target position. The opposite tilt orientation at
      the retinotopic location altered the effects induced by spatiotopic adaptation.
      More precisely, it cancelled out spatiotopic adaptation at the saccade target
      location. We conclude that retinotopic and spatiotopic visual adaptation are
      independent effects.

PMID- 29049594
TI  - The perceptual dimensions of natural dynamic flow.
AB  - We measured perceptual judgments of category, material attributes, affordances,
      and similarity to investigate the perceptual dimensions underlying the visual
      representation of a broad class of natural dynamic flows (sea waves, smoke, and
      windblown foliage). The dynamic flows were looped 3-s movies windowed with
      circular apertures of two sizes to manipulate the level of spatial context. In
      low levels of spatial context (smaller apertures), human observers' judgments of
      material attributes and affordances were inaccurate, with estimates biased toward
      assumptions that the flows resulted from objects that were rigid, "pick-up-able,"
      and not penetrable. The similarity arrangements showed dynamic flow clusters
      based partly on material, but dominated by color appearance. In high levels of
      spatial context (large apertures), observers reliably estimated material
      categories and their attributes. The similarity arrangements were based primarily
      on categories related to external, physical causes. Representational similarity
      analysis suggests that while shallow dimensions like color sometimes account for
      inferences of physical causes in the low-context condition, shallow dimensions
      cannot fully account for these inferences in the high-context condition. For the
      current broad data set of dynamic flows, the perceptual dimensions that best
      account for the similarity arrangements in the high-context condition are related
      to the intermolecular bond strength of a material's underlying physical
      structure. These arrangements are also best related to affordances that underlie
      common motor activities. Thus, the visual system appears to use an efficient
      strategy to resolve flow ambiguity; vision will sometimes rely on local, image
      based, statistical properties that can support reliable inference of external
      physical causes, and other times it uses deeper causal knowledge to interpret and
      use flow information to the extent that it is useful for everyday action
      decisions.

PMID- 29049595
TI  - To search or to like: Mapping fixations to differentiate two forms of incidental
      scene memory.
AB  - We employed eye-tracking to investigate how performing different tasks on scenes
      (e.g., intentionally memorizing them, searching for an object, evaluating
      aesthetic preference) can affect eye movements during encoding and subsequent
      scene memory. We found that scene memorability decreased after visual search (one
      incidental encoding task) compared to intentional memorization, and that
      preference evaluation (another incidental encoding task) produced better memory,
      similar to the incidental memory boost previously observed for words and faces.
      By analyzing fixation maps, we found that although fixation map similarity could
      explain how eye movements during visual search impairs incidental scene memory,
      it could not explain the incidental memory boost from aesthetic preference
      evaluation, implying that implicit mechanisms were at play. We conclude that not
      all incidental encoding tasks should be taken to be similar, as different
      mechanisms (e.g., explicit or implicit) lead to memory enhancements or decrements
      for different incidental encoding tasks.

PMID- 29049596
TI  - Working Memory and Speech Comprehension in Older Adults With Hearing Impairment.
AB  - Purpose: This study examined the relationship between working memory (WM) and
      speech comprehension in older adults with hearing impairment (HI). It was
      hypothesized that WM would explain significant variance in speech comprehension
      measured in multitalker babble (MTB). Method: Twenty-four older (59-73 years)
      adults with sensorineural HI participated. WM capacity (WMC) was measured using 3
      complex span tasks. Speech comprehension was assessed using multiple passages,
      and speech identification ability was measured using recall of sentence final
      word and key words. Speech measures were performed in quiet and in the presence
      of MTB at + 5 dB signal-to-noise ratio. Results: Results suggested that
      participants' speech identification was poorer in MTB, but their ability to
      comprehend discourse in MTB was at least as good as in quiet. WMC did not explain
      significant variance in speech comprehension before and after controlling for age
      and audibility. However, WMC explained significant variance in low-context
      sentence key words identification in MTB. Conclusions: These results suggest that
      WMC plays an important role in identifying low-context sentences in MTB, but not
      when comprehending semantically rich discourse passages. In general, data did not
      support individual variability in WMC as a factor that predicts speech
      comprehension ability in older adults with HI.

PMID- 29049597
TI  - Introduction to the Research Symposium Forum.
AB  - Purpose: The purpose of this introduction is to provide an overview of the
      articles contained within this research forum of JSLHR. Each of these articles is
      based upon presentations from the 2016 ASHA Research Symposium.

PMID- 29049599
TI  - Auditory Scene Analysis: An Attention Perspective.
AB  - Purpose: This review article provides a new perspective on the role of attention
      in auditory scene analysis. Method: A framework for understanding how attention
      interacts with stimulus-driven processes to facilitate task goals is presented.
      Previously reported data obtained through behavioral and electrophysiological
      measures in adults with normal hearing are summarized to demonstrate attention
      effects on auditory perception-from passive processes that organize unattended
      input to attention effects that act at different levels of the system. Data will
      show that attention can sharpen stream organization toward behavioral goals,
      identify auditory events obscured by noise, and limit passive processing
      capacity. Conclusions: A model of attention is provided that illustrates how the
      auditory system performs multilevel analyses that involve interactions between
      stimulus-driven input and top-down processes. Overall, these studies show that
      (a) stream segregation occurs automatically and sets the basis for auditory event
      formation; (b) attention interacts with automatic processing to facilitate task
      goals; and (c) information about unattended sounds is not lost when selecting one
      organization over another. Our results support a neural model that allows
      multiple sound organizations to be held in memory and accessed simultaneously
      through a balance of automatic and task-specific processes, allowing flexibility
      for navigating noisy environments with competing sound sources. Presentation
      Video: http://cred.pubs.asha.org/article.aspx?articleid=2601618.

PMID- 29049600
TI  - Speech Perception in Complex Acoustic Environments: Developmental Effects.
AB  - Purpose: The ability to hear and understand speech in complex acoustic
      environments follows a prolonged time course of development. The purpose of this
      article is to provide a general overview of the literature describing age effects
      in susceptibility to auditory masking in the context of speech recognition,
      including a summary of findings related to the maturation of processes thought to
      facilitate segregation of target from competing speech. Method: Data from
      published and ongoing studies are discussed, with a focus on synthesizing results
      from studies that address age-related changes in the ability to perceive speech
      in the presence of a small number of competing talkers. Conclusions: This review
      provides a summary of the current state of knowledge that is valuable for
      researchers and clinicians. It highlights the importance of considering listener
      factors, such as age and hearing status, as well as stimulus factors, such as
      masker type, when interpreting masked speech recognition data. Presentation
      Video: http://cred.pubs.asha.org/article.aspx?articleid=2601620.

PMID- 29049598
TI  - Cortical and Sensory Causes of Individual Differences in Selective Attention
      Ability Among Listeners With Normal Hearing Thresholds.
AB  - Purpose: This review provides clinicians with an overview of recent findings
      relevant to understanding why listeners with normal hearing thresholds (NHTs)
      sometimes suffer from communication difficulties in noisy settings. Method: The
      results from neuroscience and psychoacoustics are reviewed. Results: In noisy
      settings, listeners focus their attention by engaging cortical brain networks to
      suppress unimportant sounds; they then can analyze and understand an important
      sound, such as speech, amidst competing sounds. Differences in the efficacy of
      top-down control of attention can affect communication abilities. In addition,
      subclinical deficits in sensory fidelity can disrupt the ability to perceptually
      segregate sound sources, interfering with selective attention, even in listeners
      with NHTs. Studies of variability in control of attention and in sensory coding
      fidelity may help to isolate and identify some of the causes of communication
      disorders in individuals presenting at the clinic with "normal hearing."
      Conclusions: How well an individual with NHTs can understand speech amidst
      competing sounds depends not only on the sound being audible but also on the
      integrity of cortical control networks and the fidelity of the representation of
      suprathreshold sound. Understanding the root cause of difficulties experienced by
      listeners with NHTs ultimately can lead to new, targeted interventions that
      address specific deficits affecting communication in noise. Presentation Video:
      http://cred.pubs.asha.org/article.aspx?articleid=2601617.

PMID- 29049602
TI  - Speech Understanding in Complex Listening Environments by Listeners Fit With
      Cochlear Implants.
AB  - Purpose: The aim of this article is to summarize recent published and unpublished
      research from our 2 laboratories on improving speech understanding in complex
      listening environments by listeners fit with cochlear implants (CIs). Method: CI
      listeners were tested in 2 listening environments. One was a simulation of a
      restaurant with multiple, diffuse noise sources, and the other was a cocktail
      party with 2 spatially separated point sources of competing speech. At issue was
      the value of the following sources of information, or interventions, on speech
      understanding: (a) visual information, (b) adaptive beamformer microphones and
      remote microphones, (c) bimodal fittings, that is, a CI and contralateral low
      frequency acoustic hearing, (d) hearing preservation fittings, that is, a CI with
      preserved low-frequency acoustic in the same ear plus low-frequency acoustic
      hearing in the contralateral ear, and (e) bilateral CIs. Results: A remote
      microphone provided the largest improvement in speech understanding. Visual
      information and adaptive beamformers ranked next, while bimodal fittings,
      bilateral fittings, and hearing preservation provided significant but less
      benefit than the other interventions or sources of information. Only bilateral
      CIs allowed listeners high levels of speech understanding when signals were roved
      over the frontal plane. Conclusions: The evidence supports the use of bilateral
      CIs and hearing preservation surgery for best speech understanding in complex
      environments. These fittings, when combined with visual information and
      microphone technology, should lead to high levels of speech understanding by CI
      patients in complex listening environments. Presentation Video:
      http://cred.pubs.asha.org/article.aspx?articleid=2601622.

PMID- 29049603
TI  - Enhancing Auditory Selective Attention Using a Visually Guided Hearing Aid.
AB  - Purpose: Listeners with hearing loss, as well as many listeners with clinically
      normal hearing, often experience great difficulty segregating talkers in a
      multiple-talker sound field and selectively attending to the desired "target"
      talker while ignoring the speech from unwanted "masker" talkers and other sources
      of sound. This listening situation forms the classic "cocktail party problem"
      described by Cherry (1953) that has received a great deal of study over the past
      few decades. In this article, a new approach to improving sound source
      segregation and enhancing auditory selective attention is described. The
      conceptual design, current implementation, and results obtained to date are
      reviewed and discussed in this article. Method: This approach, embodied in a
      prototype "visually guided hearing aid" (VGHA) currently used for research,
      employs acoustic beamforming steered by eye gaze as a means for improving the
      ability of listeners to segregate and attend to one sound source in the presence
      of competing sound sources. Results: The results from several studies demonstrate
      that listeners with normal hearing are able to use an attention-based "spatial
      filter" operating primarily on binaural cues to selectively attend to one source
      among competing spatially distributed sources. Furthermore, listeners with
      sensorineural hearing loss generally are less able to use this spatial filter as
      effectively as are listeners with normal hearing especially in conditions high in
      "informational masking." The VGHA enhances auditory spatial attention for speech
      on-speech masking and improves signal-to-noise ratio for conditions high in
      "energetic masking." Visual steering of the beamformer supports the coordinated
      actions of vision and audition in selective attention and facilitates following
      sound source transitions in complex listening situations. Conclusions: Both
      listeners with normal hearing and with sensorineural hearing loss may benefit
      from the acoustic beamforming implemented by the VGHA, especially for nearby
      sources in less reverberant sound fields. Moreover, guiding the beam using eye
      gaze can be an effective means of sound source enhancement for listening
      conditions where the target source changes frequently over time as often occurs
      during turn-taking in a conversation. Presentation Video:
      http://cred.pubs.asha.org/article.aspx?articleid=2601621.

PMID- 29049601
TI  - Age-Related Changes in Objective and Subjective Speech Perception in Complex
      Listening Environments.
AB  - Purpose: A frequent complaint by older adults is difficulty communicating in
      challenging acoustic environments. The purpose of this work was to review and
      summarize information about how speech perception in complex listening situations
      changes across the adult age range. Method: This article provides a review of age
      related changes in speech understanding in complex listening environments and
      summarizes results from several studies conducted in our laboratory. Results:
      Both degree of high frequency hearing loss and cognitive test performance limit
      individuals' ability to understand speech in difficult listening situations as
      they age. The performance of middle-aged adults is similar to that of younger
      adults in the presence of noise maskers, but they experience substantially more
      difficulty when the masker is 1 or 2 competing speech messages. For the most
      part, middle-aged participants in studies conducted in our laboratory reported as
      much self-perceived hearing problems as did older adult participants.
      Conclusions: Research supports the multifactorial nature of listening in real
      world environments. Current audiologic assessment practices are often
      insufficient to identify the true speech understanding struggles that individuals
      experience in these situations. This points to the importance of giving weight to
      patients' self-reported difficulties. Presentation Video:
      http://cred.pubs.asha.org/article.aspx?articleid=2601619.

PMID- 29049608
TI  - Acute administration of oestradiol or progesterone in a spinal cord ischaemia
      reperfusion model in rats.
AB  - OBJECTIVES: Despite research into protective pharmacological adjuncts, paraplegia
      persists as a dreaded complication after thoracic and thoracoabdominal aortic
      interventions. Reports on gender-related neurological outcomes after ischaemic
      and traumatic brain injuries have led to increased interest in hormonal
      neuroprotective effects and have generated other studies seeking to prove the
      neuroprotective effects of the therapeutic administration of 17beta-oestradiol
      and of progesterone. We hypothesised that acute administration of oestradiol or
      progesterone would prevent or attenuate spinal cord ischaemic injury induced by
      occlusion of the descending thoracic aorta. METHODS: Male rats were divided into
      groups receiving 280 ug/kg of 17beta-oestradiol or 4 mg/kg of progesterone or
      vehicle 30 min before transitory endovascular occlusion of the proximal
      descending thoracic aorta for 12 min. Hindlimb motor function was assessed by a
      functional grading scale (that of Basso, Beattie and Bresnahan) for 14 days after
      reperfusion. On the 14th day, a segment of the thoracolumbar spinal cord was
      harvested and prepared for histological and immunohistochemical analyses.
      RESULTS: There was significant impairment of the motor function of the hindlimb
      in the 3 study groups, with partial improvement noticed over time, but no
      difference was detected between the groups. On Day 1 of assessment, the 17beta
      oestradiol group had a functional score of 9.8 (0.0-16.5); the progesterone
      group, a score of 0.0 (0-17.1) and the control group, a score of 6.5 (0-16.9); on
      the 14th day, the 17beta-oestradiol group had a functional score of 18.0 (4.4
      19.4); the progesterone group had a score of 7.5 (0-18.5) and the control group
      had a score of 17.0 (0-19.9). Analysis of the grey matter showed that the number
      of viable neurons per section was not different between the study groups on the
      14th day. Immunostaining of the spinal cord grey matter was also similar among
      the 3 groups. CONCLUSIONS: Acute administration of oestradiol or of progesterone
      30 min before transitory occlusion of the proximal descending thoracic aorta of
      male rats could not prevent or attenuate spinal cord ischaemic injury based on an
      analysis of functional and histological outcomes.

PMID- 29049610
TI  - Progressive Acute Abdominal Pain.

PMID- 29049609
TI  - Usefulness of near-infrared angiography for identifying the intersegmental plane
      and vascular supply during video-assisted thoracoscopic segmentectomy.
AB  - OBJECTIVES: Segmentectomy by video-assisted thoracoscopic surgery (VATS) permits
      anatomical resection for diagnosis and treatment of small lung nodules but
      requires that intersegmental planes and segmental vessels be identified
      accurately. Near-infrared angiography with systemic injection of indocyanine
      green (ICG) can precisely identify the intersegmental plane. The purpose of this
      study was to confirm the usefulness of ICG angiography during VATS segmentectomy.
      METHODS: We retrospectively reviewed the records of 22 consecutive patients who
      underwent VATS segmentectomy performed with near-infrared angiography between
      November 2014 and October 2015. Segments were localized and anatomical vascular
      supply was identified on preoperative computed tomography scans. VATS
      segmentectomy was performed using an anterior approach with 2 ports and 1 non
      spreading minithoracotomy, with ICG injected systemically after arterial
      ligation. RESULTS: VATS was feasible for all 22 segmentectomies, and in all
      patients, the intersegmental plane was identified accurately by ICG angiography.
      This angiography method was also useful in patients whose anatomical vascular
      segmentation was difficult to identify and, in a few patients, to assess the
      distribution of an artery before sectioning, to determine the vascular supply of
      the remaining lung and to distinguish between segmental and intersegmental veins.
      The postoperative course was uneventful for 18 patients and complicated for 2
      patients who had prolonged air leak (10 and 15 days) with pneumonia, 1 patient
      with gastroparesis and 1 with colonic ileus. The drain was removed before the 3rd
      postoperative day in all but 2 patients, and the mean hospital stay was 5.4 +/-
      4.5 days. Anatomopathological examination indicated that 4 benign lesions and 18
      primary lung cancers were completely removed, including 14 that were Stage IA, 2
      Stage IIA and 2 Stage IIIA. CONCLUSIONS: Indocyanine green angiography provides
      technical support for identifying the intersegmental plane and the vasculature
      during VATS segmentectomy. It contributes to the quality of diagnostic and
      therapeutic excisions of small nodules that are often not visible and not
      palpable during VATS.

PMID- 29049611
TI  - Association of a Prophylactic Surgical Approach to Stage IV Small Intestinal
      Neuroendocrine Tumors With Survival.
AB  - Importance: Primary tumor resection and mesenteric lymph node dissection in
      asymptomatic patients with stage IV small intestinal neuroendocrine tumors (SI
      NETs) are controversial. Objective: To determine the association of locoregional
      surgery (LRS) performed at diagnosis with outcomes in patients with asymptomatic
      SI-NETs and distant metastases. Design, Setting, and Participants: This cohort
      study included asymptomatic patients with stage IV SI-NETs diagnosed from January
      1, 1985, through December 31, 2015, and identified using the prospective database
      of SI-NETs from Uppsala University Hospital, Uppsala, Sweden. Patients included
      were treated at a tertiary referral center and followed up until May 31, 2016,
      with data from the Swedish National Patient Register. The 363 patients with stage
      IV SI-NETs without abdominal symptoms were divided between those who underwent
      prophylactic up-front surgery within 6 months from diagnosis combined with
      oncologic treatment (hereafter referred to as LRS group [n = 161]) and those who
      underwent nonsurgical treatment or delayed surgery as needed combined with
      oncologic treatment (hereafer referred to as delayed LRS group [n = 202]).
      Exposures: Prophylactic up-front surgery within 6 months from diagnosis combined
      with oncologic treatment vs nonsurgical treatment or delayed surgery as needed
      combined with oncologic treatment. Main Outcomes and Measures: Overall survival
      (OS), length of hospital stay (LOS), postoperative morbidity and mortality, and
      reoperation rates measured from baseline. Propensity score matching was performed
      between the 2 groups. Results: The 363 patients included 173 women (47.7%) and
      190 men (52.3%), with a mean (SD) age at diagnosis of 62.4 (11.1) years. Two
      isonumerical groups with 91 patients in each resulted after propensity score
      matching. The LRS and delayed LRS groups were comparable in median OS (7.9 years
      [range, 5.1-10.7 years] vs 7.6 years [range, 5.8-9.5 years]; hazard ratio [HR],
      0.98; 95% CI, 0.70-1.37; log-rank P = .93) and cancer-specific survival (7.7
      years [range, 4.5-10.8 years] vs 7.6 years [range, 5.6-9.7 years]; HR, 0.99; 95%
      CI, 0.71-1.40; log-rank P = .99). No difference was found in 30-day mortality (0
      patients in both matched groups) or postoperative morbidity (2 [2.2%] vs 1
      [1.1%]; P > .99), median LOS (73 days [range, 2-270 days] vs 76 days [range, 0
      339 days]; P = .64) or LOS due to local tumor-related symptoms (7.0 days [range,
      0-90 days] vs 11.5 days [range, 0-69 days]; P = .81), or incisional hernia
      repairs (4 patients [4.4%] in both groups; P > .99). Patients in the LRS group
      underwent more reoperative procedures (13 [14.3%]) compared with those in the
      delayed LRS group (3 [3.3%]) owing to intestinal obstruction (P < .001).
      Conclusions and Relevance: Prophylactic up-front LRS conferred no survival
      advantage in asymptomatic patients with stage IV SI-NETs. Delayed surgery as
      needed was comparable in all examined outcomes and was associated with fewer
      reoperations for intestinal obstruction. The value of a priori LRS in the
      presence of distant metastases is challenged and needs to be elucidated in a
      randomized clinical study.

PMID- 29049613
TI  - Hybrid operating room Dyna-computed tomography combined image-guided
      electromagnetic navigation bronchoscopy dye marking and hookwire localization
      video-assisted thoracic surgery metastasectomy.
AB  - Hybrid operating room Dyna-computed tomography imaging is increasingly recognized
      as an important adjunct for management of small pulmonary lesions, either for
      biopsy or for localization to guide surgical resection. We describe for the first
      time the combined hybrid operating room Dyna-computed tomography image-guided
      electromagnetic navigation bronchoscopy dye marking and hookwire localization
      approach to localize multiple sub-centimetre nodules for video-assisted thoracic
      surgery metastasectomy. Furthermore, such complex set of procedures can be safely
      and effectively performed within one operating environment, maximizing work
      efficiency and minimizing the potential for complications.

PMID- 29049607
TI  - Dose-Response Association of CD8+ Tumor-Infiltrating Lymphocytes and Survival
      Time in High-Grade Serous Ovarian Cancer.
AB  - Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in
      immune control of epithelial ovarian cancer; however, little is known about
      prognostic patterns of CD8+ TILs by histotype and in relation to other clinical
      factors. Objective: To define the prognostic role of CD8+ TILs in epithelial
      ovarian cancer. Design, Setting, and Participants: This was a multicenter
      observational, prospective survival cohort study of the Ovarian Tumor Tissue
      Analysis Consortium. More than 5500 patients, including 3196 with high-grade
      serous ovarian carcinomas (HGSOCs), were followed prospectively for over 24 650
      person-years. Exposures: Following immunohistochemical analysis, CD8+ TILs were
      identified within the epithelial components of tumor islets. Patients were
      grouped based on the estimated number of CD8+ TILs per high-powered field:
      negative (none), low (1-2), moderate (3-19), and high (>=20). CD8+ TILs in a
      subset of patients were also assessed in a quantitative, uncategorized manner,
      and the functional form of associations with survival was assessed using
      penalized B-splines. Main Outcomes and Measures: Overall survival time. Results:
      The final sample included 5577 women; mean age at diagnosis was 58.4 years
      (median, 58.2 years). Among the 5 major invasive histotypes, HGSOCs showed the
      most infiltration. CD8+ TILs in HGSOCs were significantly associated with longer
      overall survival; median survival was 2.8 years for patients with no CD8+ TILs
      and 3.0 years, 3.8 years, and 5.1 years for patients with low, moderate, or high
      levels of CD8+ TILs, respectively (P value for trend = 4.2 * 10-16). A survival
      benefit was also observed among women with endometrioid and mucinous carcinomas,
      but not for those with the other histotypes. Among HGSOCs, CD8+ TILs were
      favorable regardless of extent of residual disease following cytoreduction, known
      standard treatment, and germline BRCA1 pathogenic mutation, but were not
      prognostic for BRCA2 mutation carriers. Evaluation of uncategorized CD8+ TIL
      counts showed a near-log-linear functional form. Conclusions and Relevance: This
      study demonstrates the histotype-specific nature of immune infiltration and
      provides definitive evidence for a dose-response relationship between CD8+ TILs
      and HGSOC survival. That the extent of infiltration is prognostic, not merely its
      presence or absence, suggests that understanding factors that drive infiltration
      will be the key to unraveling outcome heterogeneity in this cancer.

PMID- 29049612
TI  - Long-term Change in the Risk of Skin Cancer After Organ Transplantation: A
      Population-Based Nationwide Cohort Study.
AB  - Importance: The high risk of skin cancer after organ transplantation is a major
      clinical challenge and well documented, but reports on temporal trends in the
      risk of posttransplant cutaneous squamous cell carcinoma (SCC) are few and appear
      contradictory. Objective: To study temporal trends for the risk of skin cancer,
      particularly SCC, after organ transplantation. Design, Setting, and Participants:
      Population-based, nationwide, prospective cohort study of 8026 patients receiving
      a kidney, heart, lung, or liver transplant in Norway from 1968 through 2012 using
      patient data linked to a national cancer registry. The study was conducted in a
      large organ transplantation center that serves the entire Norwegian population of
      approximately 5.2 million. Exposures: Receiving a solid organ transplant owing to
      late-stage organ failure, followed by long-term immunosuppressive treatment
      according to graft-specific treatment protocols. Main Outcomes and Measures:
      Occurrence of first posttransplant SCC, melanoma, or Kaposi sarcoma of the skin.
      Risk of skin cancer was analyzed using standardized incidence ratios (SIRs) and,
      for SCC, multivariable Poisson regression analysis of SIR ratios, adjusting for 5
      year time period of transplantation, different follow-up time, age, sex, and type
      of organ. Results: The study cohort included 8026 organ transplant recipients,
      5224 men (65.1%), with a mean age at transplantation of 48.5 years. Median follow
      up time was 6.7 years per recipient; total follow-up time, 69 590 person-years.
      The overall SIRs for SCC, melanoma, and Kaposi sarcoma were 51.9 (95% CI, 48.4
      55.5), 2.4 (95% CI, 1.9-3.0), and 54.9 (95% CI, 27.4-98.2), respectively. In
      those who underwent transplantation in the 1983-1987 period, the unadjusted SIR
      for SCC was 102.7 (95%, 85.8-122.1), declining to 21.6 (95% CI, 16.8-27.0) in
      those who underwent transplantation in the 2003-2007 period. Adjusting for
      different follow-up times and background population risks, as well as age, graft
      organ, and sex, a decline in the SIR for SCC was found, with SIR peaking in
      patients who underwent transplantation in the 1983-1987 period and later
      declining to less than half in patients who underwent transplantation in the 1998
      2002, 2003-2007, and 2008-2012 periods, with the relative SIRs being 0.42 (95%
      CI, 0.32-0.55), 0.31 (95% CI, 0.22-0.42), and 0.44 (95% CI, 0.30-0.66),
      respectively. Conclusions and Relevance: The risk of SCC after organ
      transplantation has declined significantly since the mid-1980s in Norway. Less
      aggressive and more individualized immunosuppressive treatment and close clinical
      follow-up may explain the decline. Still, the risk of SCC in organ transplant
      recipients remains much higher than in the general population and should be of
      continuous concern for dermatologists, transplant physicians, and patients.

PMID- 29049614
TI  - Anticoagulation management following left ventricular assist device implantation
      is similar across all provider strategies.
AB  - OBJECTIVES: Thromboembolic and bleeding events are potential complications
      following left ventricular assist device implantation. A tight control of the
      international normalized ratio (INR) is believed to be crucial in the reduction
      of postimplant complications. There is significant variability among institutions
      as to whether a device implanting centre should be managing the INR. In this
      study, we evaluated the effect of INR management strategies in maintaining a
      therapeutic INR. METHODS: A retrospective review was utilized to identify
      patients implanted with either the HeartMate II or the HeartWare HVAD between
      January 2011 and February 2016. Patients were stratified into 4 groups based on
      the post-discharge INR management strategy: outside hospital system
      anticoagulation clinic, outside hospital primary care provider, implanting centre
      anticoagulation clinic or implanting centre ventricular assist device office. The
      INR data were collected and analysed for both the early (discharge, 7, 14, 21 and
      30 days) and late (3, 6, 9 and 12 months) postoperative periods. RESULTS: There
      were 163 patients identified during the study period who met the study inclusion
      criteria: 49 (30%) patients were managed by an outside hospital system
      anticoagulation clinic, 59 (36.2%) patients by an outside hospital
      physician/primary care provider, 22 (13.5%) patients by the implanting centre
      anticoagulation clinic and 33 (20.2%) patients by the implanting centre
      ventricular assist device office. There were no statistically significant
      differences found between management strategies across all time points.
      CONCLUSIONS: There was no statistically significant difference found between the
      management strategies examined. Regardless of the chosen INR management strategy,
      patients have similar INR values and postoperative outcomes.

PMID- 29049615
TI  - Current Trends in Management of Submental Liposis: A Pooled Analysis and Survey.
AB  - Importance: Since its approval by the US Food and Drug Administration for
      treatment of moderate to severe submental liposis in April 2015, deoxycholic acid
      (Kybella) has received significant media attention as a novel aesthetic
      treatment. Four phase 3 clinical trials have published data demonstrating the
      safety and efficacy of the drug compared with placebo; however, no study has
      juxtaposed the product with submental liposuction. Objective: To evaluate the
      efficacy of injectable deoxycholic acid in the treatment of isolated submental
      liposis. Evidence Review: A pooled analysis of the data from the 2 European and 2
      North American phase 3 clinical trials was performed by grouping the study
      participants by treatment arm to analyze efficacy, adverse effects, and treatment
      variables. Members of the American Academy of Facial Plastic and Reconstructive
      Surgery (AAFPRS) were also surveyed regarding their clinical use of deoxycholic
      acid, fees, and adverse events. Findings: The pooled analysis included 1738
      unique patients (348 men [20.0%] and 1390 women [80.0%]; mean [SD] age, 47.7
      [1.6] years) and revealed that all studies demonstrated efficacy compared with
      placebo. However, a significant number of patients experienced pain, edema, and
      numbness after injection. The clinical trial population was injected with a mean
      (SD) of 186.0 (106.6) mg of drug per patient during the course of treatment. A
      total of 102 members responded to the survey, representing 4% of AAFPRS
      membership. Based on the results of the survey, clinicians reported charging a
      mean (SD) of $691.04 ($168.68) per 20-mg vial of deoxycholic acid, resulting in a
      cost of $6426.35 per study participant. The survey revealed a mean (SD) total
      cost to the patient for submental liposuction to be $2976.56 ($1041.62).
      Conclusions and Relevance: Although the clinical trials demonstrated functional
      drug efficacy, the large volume of drug used precluded cost-effectiveness. The
      survey found clinical practice to differ from the protocols used in the trials.
      Deoxycholic acid may be only fiscally efficacious for patients with mild to
      moderate submental liposis who require only 20 to 30 mg of drug per treatment for
      3 treatment sessions. Level of Evidence: 1.

PMID- 29049616
TI  - An uncommon variant of double-chambered right ventricle masquerading as double
      chambered left ventricle.
AB  - We present a rare case of a double-chambered right ventricle masquerading as a
      double-chambered left ventricle, which was found incidentally on cardiac imaging
      in an adult female patient with atypical chest pain. The most common form of
      double-chambered right ventricle is characterized by compartmentalization of the
      right ventricle by muscular bands into 2 distinct chambers. The main features of
      this malformation are a pressure gradient between the 2 compartments, and the
      frequent (up to 90%) association with a membranous ventricular septal defect. In
      our case, the muscular band dividing the right ventricle was located in the
      inferoseptal part of the latter, creating a diminutive cavity that had no
      communication with the main right ventricle but communicated with the left
      ventricle creating the false impression of a double-chambered left ventricle.
      This constitutes a rare variant of double-chambered right ventricle with unknown
      clinical implications.

PMID- 29049617
TI  - Survival results of postoperative coronary angiogram for treatment of
      perioperative myocardial ischaemia following coronary artery bypass grafting: a
      single-centre experience.
AB  - OBJECTIVES: Although perioperative myocardial ischaemia (PMI) is a well-known
      complication following coronary artery bypass grafting (CABG), standard
      strategies for its diagnosis and treatment are so far not defined. In this study,
      we sought to evaluate the impact on survival of postoperative coronary angiogram
      for management of patients with PMI after CABG. METHODS: Overall, 4028 patients
      underwent isolated CABG in a single-centre institution between January 2006 and
      September 2013. A total of 168 (4.2%) patients received postoperative coronary
      angiogram because of diagnosis of PMI. These patients were matched on the basis
      of gender, age at surgery and date of surgery, with 336 (1:2 ratio) CABG patients
      without PMI to determine the impact of the PMI management. RESULTS: A total of
      476 grafts were examined (263 venous grafts, 196 internal mammary artery grafts
      and 17 radial artery grafts). Almost three-quarters of the 168 PMI (74.4%)
      patients underwent postoperative coronary angiogram within 24 h of surgery.
      Normal postoperative coronary angiogram, graft failure and new native vessels
      occlusion were observed in 23.2%, 52.4% and 24.4% of patients, respectively. A
      total of 30 (17.9%) patients underwent surgical revision of grafts, whereas 60
      (35.7%) patients were treated with percutaneous coronary intervention. Eighteen
      (10.7%) PMI patients died during the hospital stay compared with 6 (1.8%)
      patients in the non-PMI group. Survival rates at 7 years were 62.5% in the PMI
      group and 81.1% in non-PMI group (P < 0.001). After multivariable adjustment PMI
      (P < 0.001; hazard ratio 3.17, 95% confidence interval 2.12-4.73) turned out to
      be an independent predictor of mortality on follow-up. Moreover, further
      subanalysis revealed that delayed postoperative coronary angiogram (>24 h after
      surgery) was an independent predictor of poorer mid-term survival (P = 0.008;
      hazard ratio 3.62, 95% confidence interval 1.41-9.33). CONCLUSIONS: PMI after
      CABG is associated with a significantly poorer survival. A prompt postoperative
      management must always be considered. Further prospective studies are required to
      confirm our results.

PMID- 29049618
TI  - Introduction: Hearing Across the Lifespan (HEAL) 2016.
AB  - Purpose: This introduction overviews this special issue on the Hearing Across the
      Lifespan (HEAL) conference, which was held in Cernobbio, Italy, June 2-4, 2016.

PMID- 29049619
TI  - Field Monitoring of Otoacoustic Emissions During Noise Exposure: Pilot Study in
      Controlled Environment.
AB  - Purpose: In spite of all the efforts to implement workplace hearing conservation
      programs, noise-induced hearing loss remains the leading cause of disability for
      North American workers. Nonetheless, an individual's susceptibility to noise
      induced hearing loss can be estimated by monitoring changes in hearing status in
      relation to the level of ambient noise exposure. The purpose of this study was to
      validate an approach that could improve workplace hearing conservation practices.
      The approach was developed using a portable and robust system designed for noisy
      environments and consisted of taking continuous measurements with high temporal
      resolution of the health status of the inner ear using otoacoustic emissions
      (OAEs). Method: A pilot study was conducted in a laboratory, exposing human
      subjects to industrial noise recordings at realistic levels. In parallel, OAEs
      were measured periodically using the designed OAE system as well as with a
      commercially available OAE system, used as a reference. Results: Variations in
      OAE levels were analyzed and discussed along with the limitations of the
      reference and designed systems. Conclusions: This study demonstrates that the
      monitoring of an individual's OAEs could be useful in monitoring temporary
      changes in hearing status induced by exposure to ambient noise and could be
      considered as a new tool for effective hearing conservation programs in the
      workplace.

PMID- 29049620
TI  - Diagnosing and Screening in a Minority Language: A Validation Study.
AB  - Purpose: The Turkish Digit Triplet Test for hearing self-screening purposes and
      the Turkish Matrix Test (TURMatrix) for follow-up hearing diagnostics offer an
      automated closed-set response format where patients respond by choosing from
      response alternatives. Their applicability for testing Turkish-speaking patients
      in their native language by German audiologists with different Turkish language
      skills was investigated. Method: Tests were composed of spoken numbers (Turkish
      Digit Triplet Test) or sentences (TURMatrix). For 49 participants differing in
      hearing ability, speech reception thresholds (SRTs) in noise and quiet were
      obtained, for the TURMatrix with either the open- or closed-set response format,
      by audiologists with and without Turkish language skills, respectively. Results:
      SRTs of both tests correlate closely with each other as well as with hearing
      ability, but not as closely as individual SRTs in quiet with hearing ability.
      SRTs in noise of listeners with normal hearing were about 0.7 dB lower for the
      closed-set than for the open-set response format. Conclusions: The 2 tests yield
      comparable results and are applicable to professionals without suitable language
      skills. For the closed-set response format of the TURMatrix, literacy is crucial
      and supplemental (visual) cues improve performance. Speech audiometry in noise
      should assess suprathreshold processing deficits independently from language
      proficiency in the majority language.

PMID- 29049621
TI  - Autonomic Nervous System Responses to Hearing-Related Demand and Evaluative
      Threat.
AB  - Purpose: This paper consists of 2 parts. The purpose of Part 1 was to review the
      potential influence of internal (person-related) factors on listening effort. The
      purpose of Part 2 was to present, in support of Part 1, preliminary data
      illustrating the interactive effects of an external factor (task demand) and an
      internal factor (evaluative threat) on autonomic nervous system measures. Method:
      For Part 1, we provided a brief narrative review of motivation and stress as
      modulators of listening effort. For Part 2, we described preliminary data from a
      study using a repeated-measures (2 * 2) design involving manipulations of task
      demand (high, low) and evaluative threat (high, low). The low-demand task
      consisted of repetition of sentences from a narrative. The high-demand task
      consisted of answering questions about the narrative, requiring both
      comprehension and recall. During the high evaluative threat condition,
      participants were filmed and told that their video recordings would be evaluated
      by a panel of experts. During the low evaluative threat condition, no filming
      occurred; participants were instructed to "do your best." Skin conductance
      (sympathetic nervous system activity) and heart rate variability (HRV,
      parasympathetic activity) were measured during the listening tasks. The HRV
      measure was the root mean square of successive differences of adjacent interbeat
      intervals. Twelve adults with hearing loss participated. Results: Skin
      conductance increased and HRV decreased relative to baseline (no task) for all
      listening conditions. Skin conductance increased significantly with an increase
      in evaluative threat, but only for the more demanding task. There was no
      significant change in HRV in response to increasing evaluative threat or task
      demand. Conclusions: Listening effort may be influenced by factors other than
      task difficulty, as reviewed in Part 1. This idea is supported by the preliminary
      data indicating that the sympathetic nervous system response to task demand is
      modulated by social evaluative threat. More work is needed to determine the
      relative contributions of motivation and emotional stress on physiological
      responses during listening tasks.

PMID- 29049622
TI  - Relation Between Listening Effort and Speech Intelligibility in Noise.
AB  - Purpose: Subjective ratings of listening effort might be applicable to estimate
      hearing difficulties at positive signal-to-noise ratios (SNRs) at which speech
      intelligibility scores are near 100%. Hence, ratings of listening effort were
      compared with speech intelligibility scores at different SNRs, and the benefit of
      hearing aids was evaluated. Method: Two groups of listeners, 1 with normal
      hearing and 1 with hearing impairment, performed adaptive speech intelligibility
      and adaptive listening effort tests (Adaptive Categorical Listening Effort
      Scaling; Krueger, Schulte, Brand, & Holube, 2017) with sentences of the Oldenburg
      Sentence Test (Wagener, Brand, & Kollmeier, 1999a, 1999b; Wagener, Kuhnel, &
      Kollmeier, 1999) in 4 different maskers. Model functions were fitted to the data
      to estimate the speech reception threshold and listening effort ratings for
      extreme effort and no effort. Results: Listeners with hearing impairment showed
      higher rated listening effort compared with listeners with normal hearing. For
      listeners with hearing impairment, the rating extreme effort, which corresponds
      to negative SNRs, was more correlated to the speech reception threshold than the
      rating no effort, which corresponds to positive SNRs. A benefit of hearing aids
      on speech intelligibility was only verifiable at negative SNRs, whereas the
      effect on listening effort showed high individual differences mainly at positive
      SNRs. Conclusion: The adaptive procedure for rating subjective listening effort
      yields information beyond using speech intelligibility to estimate hearing
      difficulties and to evaluate hearing aids.

PMID- 29049624
TI  - The ALFA4Hearing Model (At-a-Glance Labeling for Features of Apps for Hearing
      Health Care) to Characterize Mobile Apps for Hearing Health Care.
AB  - Purpose: The aim of the study was to analyze, by using the ALFA4Hearing model (At
      a-Glance Labeling for Features of Apps for Hearing Health Care), a sample of apps
      over a wide range of services in the hearing health care (HHC) domain in order to
      take a first picture of the current scenario of apps for HHC. Method: We tested
      120 apps, and we characterized them by using the ALFA4Hearing model, which
      includes 29 features in 5 components (Promoters, Services, Implementation, Users,
      and Descriptive Information). We analyzed (a) the distribution of the 29 features
      in the sample, (b) the relationship between the Implementation features and the
      Services provided by the apps, and (c) the distribution of the 29 features in
      apps for professional use. Results: The analysis of our sample of apps by means
      of the ALFA4Hearing model highlighted interesting trends and emerging challenges.
      Also, results suggested many potential opportunities for research and clinical
      practice, such as greater involvement of stakeholders, improved evidence base,
      higher technical quality, and usability. Conclusions: The ALFA4Hearing model is
      able to represent, at a glance, a large amount of information about apps for HHC,
      highlighting trends and challenges. It might be useful to HHC professionals as a
      basis for app characterization and informed decision making.

PMID- 29049623
TI  - Subjective Fatigue in Children With Hearing Loss Assessed Using Self- and Parent
      Proxy Report.
AB  - Purpose: The primary purposes of this study were to examine the effects of
      hearing loss and respondent type (self- vs. parent-proxy report) on subjective
      fatigue in children. We also examined associations between child-specific factors
      and fatigue ratings. Method: Subjective fatigue was assessed using the Pediatric
      Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS; Varni,
      Burwinkle, Katz, Meeske, & Dickinson, 2002). We compared self- and parent-proxy
      ratings from 60 children with hearing loss (CHL) and 43 children with normal
      hearing (CNH). The children ranged in age from 6 to 12 years. Results: School-age
      CHL experienced more overall and cognitive fatigue than CNH, although the
      differences were smaller than previously reported. Parent-proxy report was not
      strongly associated with child self-report, and parents tended to underestimate
      their child's fatigue, particularly sleep/rest fatigue. Language ability was also
      associated with subjective fatigue. For CHL and CNH, as language abilities
      increased, cognitive fatigue decreased. Conclusions: School-age CHL experience
      more subjective fatigue than CNH. The poor association between parent-proxy and
      child reports suggests that the parent-proxy version of the PedsQL-MFS should not
      be used in isolation when assessing fatigue in school-age children. Future
      research should examine how language abilities may modulate fatigue and its
      potential academic consequences in CHL.

PMID- 29049625
TI  - A "Goldilocks" Approach to Hearing-Aid Self-Fitting: User Interactions.
AB  - Purpose: The purpose of the current study was to evaluate user reactions to
      custom software designed for self-adjustment of amplification. Method:
      "Goldilocks" software was developed to allow user exploration and selection of
      preferred levels of overall output, low-frequency cut, and high-frequency boost
      while listening to preprocessed speech. Thirteen hearing-aid users and 13
      nonusers self-adjusted before and after taking a speech perception test
      incorporated into the software. Results: All 26 participants were able to
      complete the 2 adjustments and the intervening test in an average of 6.5 min-20
      of them from on-screen instructions without experimenter help. Relative to a
      generic starting condition, the average participant opted to increase overall
      output, reduce low-frequency cut, and increase high-frequency boost. The first
      and second self-selected values were highly correlated, but there was evidence of
      further increases of overall volume and high-frequency boost after speech
      perception testing with the initial adjustment. There was no evidence that prior
      hearing-aid experience affected the ability to understand or complete the self
      fitting process. Conclusions: This approach to hearing-aid self-fitting can be a
      speedy, reliable, and feasible alternative to, or supplement to, conventional
      fitting procedures, but many questions remain to be answered.

PMID- 29049626
TI  - Ecological Momentary Assessment: Feasibility, Construct Validity, and Future
      Applications.
AB  - Purpose: This research assessed the feasibility and construct validity of
      ecological momentary assessment in capturing the hearing experiences of adults
      with mild hearing impairment in natural environments. Method: Twenty-nine adults
      between the ages of 55 and 79 years (M = 69 years) answered multiple surveys on a
      smartphone app over a 2-week trial. Participants also wore 1 environmental
      classifier and a streamer allowing bidirectional communication between smartphone
      and classifier. Surveys were triggered based on defined criteria, or by the
      participants. A paper-based self-report questionnaire was administered before and
      after the trial. Results: Feasibility was indicated by high compliance rates,
      with a total of 1,128 surveys completed. Of these, 72% were completed during a
      listening event, 26% within 1 hr, and only 2% of the surveys more than 1 hr after
      the listening event. The mean survey completion time was 1 min 40 s. Mean pre-
      and post-trial self-report scores were not significantly different, indicating no
      reactivity. Construct validity was indicated by the close agreement between
      subjective ratings of listening situations and objective data from the hearing
      aid classifier. Conclusions: Ecological momentary assessment is a feasible and
      valid research methodology for older adults with mild hearing impairment. The
      methodology has potential as a clinical counseling and outcome tool.

PMID- 29049627
TI  - International Outcome Inventory for Hearing Aids: Data From a Large Swedish
      Quality Register Database.
AB  - Purpose: The purpose of this study was to analyze a database of completed
      International Outcome Inventory for Hearing Aids (IOI-HA) questionnaires obtained
      from over 100,000 clients fitted with new hearing aids in Sweden during the
      period of 2012-2016. Mean IOI-HA total scores were correlated with degree of
      hearing loss, unilateral versus bilateral fitting, first-time versus return
      clients, gender, and variation among dispensing clinics. The correlations with
      expectations, service quality, and technical functioning of the hearing aids were
      also analyzed. Method: Questionnaires containing the 7 IOI-HA items as well as
      questions concerning some additional issues were mailed to clients 3-6 months
      after fitting of new hearing aids. The questionnaires were returned to and
      analyzed by an independent research institute. Results: More than 100 dispensing
      clinics nationwide take part in this project. A response rate of 52.6% resulted
      in 106,631 data sets after excluding incomplete questionnaires. Forty-six percent
      of the responders were women, and 54% were men. The largest difference in mean
      score (0.66) was found for the IOI-HA item "use" between return clients and first
      time users. Women reported significantly higher (better) scores for the item
      "impact on others" compared with men. The bilaterally fitted subgroup reported
      significantly higher scores for all 7 items compared with the unilaterally fitted
      subgroup. Experienced users produced higher scores on benefit and satisfaction
      items, whereas first-time users gave higher scores for residual problems. No
      correlation was found between mean IOI-HA total score and average hearing
      threshold level (pure-tone average [PTA]). Mean IOI-HA total scores were found to
      correlate significantly with perceived service quality of the dispensing center
      and with the technical functionality of the hearing aids. Conclusions: When
      comparing mean IOI-HA total scores from different studies or between groups,
      differences with regard to hearing aid experience, gender, and unilateral versus
      bilateral fitting have to be considered. No correlation was found between mean
      IOI-HA total score and degree of hearing loss in terms of PTA. Thus, PTA is not a
      reliable predictor of benefit and satisfaction of hearing aid provision as
      represented by the IOI-HA items. Identification of a specific lower fence in PTA
      for hearing aid candidacy is therefore to be avoided. Large differences were
      found in mean IOI-HA total scores related to different dispensing centers.

PMID- 29049628
TI  - Findings From EuroTrak Surveys From 2009 to 2015: Hearing Loss Prevalence,
      Hearing Aid Adoption, and Benefits of Hearing Aid Use.
AB  - Purpose: The purpose of this study was to analyze data from the EuroTrak surveys
      performed from 2009 to 2015 in Germany, France, and the United Kingdom to
      identify factors that could account for the growth in hearing aid sales over that
      period. Method: Data of 132,028 people-approximately 15,000 for each of the 3
      countries at 3-year intervals-were collected using a questionnaire. The sample in
      each country was weighted using the respective country age-gender populations to
      get balanced results. Furthermore, 11,867 persons with self-reported hearing
      impairment filled in a comprehensive questionnaire on hearing status and related
      matters; 4,631 were hearing aid owners. Data were pooled over the 3 countries for
      each of the years 2009, 2012, and 2015 and analyzed for developments over the 6
      year period. In certain cases, data were pooled across countries and years. The
      analysis focused on hearing loss prevalence, hearing aid adoption rates,
      satisfaction with hearing aids, and benefits of hearing aid use. Results: Hearing
      loss prevalence was stable over the period around 10%-slightly higher for men
      than for women. Hearing aid adoption overall increased from 33% to 37%, and
      bilateral use increased from 55% to 69%. Intervals between hearing aid renewals
      decreased. These factors contribute to increased hearing aid sales. Bilateral
      users are more satisfied with the hearing aid product features (76%) and
      performance (72%) and use their hearing aids 9.1 hr per day, compared with
      unilateral users where the corresponding numbers are 71%, 67%, and 7.8 hr,
      respectively. Satisfaction with hearing aid product features and performance in
      general is slightly increasing; hearing aid users are 14.5% less exhausted at the
      end of the day compared with nonusers with similar hearing loss and exhibit less
      depressive and forgetfulness symptoms. Conclusions: The prevalence of self
      reported hearing loss is 10.6% and stable, and hearing aid adoption has
      increased, particularly of bilateral fittings that are more satisfactory and
      exhibit higher daily use patterns. Higher uptake of hearing aids contributes to
      growing hearing aid sales.

PMID- 29049630
TI  - Reflections on Lake Como Conferences (2000-2016).
AB  - Purpose: We present an overview of the conceptualization and development of the
      Newborn Hearing Screening and Hearing Across the Lifespan (Lake Como) conferences
      from 2000 to 2016.

PMID- 29049629
TI  - Do Older Listeners With Hearing Loss Benefit From Dynamic Pitch for Speech
      Recognition in Noise?
AB  - Purpose: Dynamic pitch, the variation in the fundamental frequency of speech,
      aids older listeners' speech perception in noise. It is unclear, however, whether
      some older listeners with hearing loss benefit from strengthened dynamic pitch
      cues for recognizing speech in certain noise scenarios and how this relative
      benefit may be associated with individual factors. We first examined older
      individuals' relative benefit between natural and strong dynamic pitches for
      better speech recognition in noise. Further, we reported the individual factors
      of the 2 groups of listeners who benefit differently from natural and strong
      dynamic pitches. Method: Speech reception thresholds of 13 older listeners with
      mild-moderate hearing loss were measured using target speech with 3 levels of
      dynamic pitch strength. Individuals' ability to benefit from dynamic pitch was
      defined as the speech reception threshold difference between speeches with and
      without dynamic pitch cues. Results: The relative benefit of natural versus
      strong dynamic pitch varied across individuals. However, this relative benefit
      remained consistent for the same individuals across those background noises with
      temporal modulation. Those listeners who benefited more from strong dynamic pitch
      reported better subjective speech perception abilities. Conclusion: Strong
      dynamic pitch may be more beneficial than natural dynamic pitch for some older
      listeners to recognize speech better in noise, particularly when the noise has
      temporal modulation.

PMID- 29049632
TI  - An Engineering Model to Test for Sensory Reweighting: Nonhuman Primates Serve as
      a Model for Human Postural Control and Vestibular Dysfunction.
AB  - Quantitative animal models are critically needed to provide proof of concept for
      the investigation of rehabilitative balance therapies (e.g., invasive vestibular
      prostheses) and treatment response prior to, or in conjunction with, human
      clinical trials. This paper describes a novel approach to modeling the nonhuman
      primate postural control system. Our observation that rhesus macaques and humans
      have even remotely similar postural control motivates the further application of
      the rhesus macaque as a model for studying the effects of vestibular dysfunction,
      as well as vestibular prosthesis-assisted states, on human postural control.
      Previously, system identification methodologies and models were only used to
      describe human posture. However, here we utilized pseudorandom, roll-tilt balance
      platform stimuli to perturb the posture of a rhesus monkey in normal and mild
      vestibular (equilibrium) loss states. The relationship between rhesus monkey
      trunk sway and platform roll-tilt was determined via stimulus-response curves and
      transfer function results. A feedback controller model was then used to explore
      sensory reweighting (i.e., changes in sensory reliance), which prevented the
      animal from falling off of the tilting platform. Conclusions involving sensory
      reweighting in the nonhuman primate for a normal sensory state and a state of
      mild vestibular loss led to meaningful insights. This first-phase effort to model
      the balance control system in nonhuman primates is essential for future
      investigations toward the effects of invasive rehabilitative (balance)
      technologies on postural control in primates, and ultimately, humans.

PMID- 29049633
TI  - Cardiopulmonary bypass does not induce lung dysfunction after pulmonary
      thrombarterectomy: role of pulmonary compliance.
AB  - OBJECTIVES: Pulmonary endarterectomy is a heavy surgical procedure that is
      performed under cardiopulmonary bypass (CPB) and aimed to cure postembolic
      pulmonary hypertension. Reperfusion oedema is both the hallmark of successful
      surgical procedure and the most frequent postoperative complication. Post-CPB
      lung dysfunction was not mentioned in any report. We undertook a study to
      determine whether post-CPB lung dysfunction was present in these patients.
      METHODS: In a retrospective cohort study with matching on some baseline
      covariates, we selected 41 patients who had undergone pulmonary endarterectomy
      and in whom pre-, intra- and postoperative records were complete. The control
      group was composed of 39 patients operated on from elective cardiac surgery
      during the same period and matched with a study group for age, gender, body mass
      index, blood creatinine, diabetes and baseline partial pressure of
      oxygen/fraction of inspired oxygen ratio. Criteria for post-CPB lung dysfunction
      were partial pressure of oxygen/fraction of inspired oxygen ratio decrease and
      bilateral basal oedema. Explanatory variables for post-CPB lung dysfunction were
      coronary arterial bypass, pleura opening, static pulmonary compliance measured at
      the time of thorax closed then retracted, fluid infusion, transfusion and
      vasopressors. RESULTS: All patients operated on from pulmonary endarterectomy
      presented radiological oedema reperfusion in surgical unblocking areas. Among
      them, only 2 had bilateral basal oedema when compared to the 24 patients from the
      control group (P < 0.001). Partial pressure of oxygen/fraction of inspired oxygen
      ratio increased in the study group and decreased in the control group (30 +/- 109
      vs -67 +/- 134 mmHg, P < 0.001). Control group patients with high-baseline
      pulmonary compliance were at risk for post-CPB lung dysfunction. CONCLUSIONS:
      Patients operated on from pulmonary endarterectomy were saved from post-CPB lung
      dysfunction. The latter could be induced by a mechanical phenomenon.

PMID- 29049635
TI  - Errors in Table.

PMID- 29049634
TI  - Internet-Based Self-Help for Meniere's Disease: Details and Outcome of a Single
      Group Open Trial.
AB  - Purpose: In this article, we present the details and the pilot outcome of an
      Internet-based self-help program for Meniere's disease (MD). Method: The Norton
      Kaplan model is applied to construct a strategic, person-focused approach in the
      enablement process. The program assesses the disorder profile and diagnosis. In
      the therapeutic component of the program, the participant defines vision and time
      frame, inspects confounding factors, determines goals, establishes a strategy,
      and starts to work on the important problems caused by the disorder. The program
      works interactively, utilizes collaboration with significant others, and enhances
      positive thinking. Participants took part in an Internet-based self-help program.
      Data were collected interactively using open-ended and structured questionnaires
      on various disease-specific and general health aspects. The pilot outcome of 41
      patients with MD was evaluated. Results: The analysis of the pilot data showed
      statistically significant improvement in their general health-related quality of
      life (p < .001). Also, the outcome of the Posttraumatic Growth Inventory (Cann et
      al., 2010) showed small to moderate change as a result of the intervention.
      Conclusions: The Internet-based self-help program can be helpful in the
      rehabilitation of patients with MD to supplement medical therapy.

PMID- 29049636
TI  - Implantable epicardial cardioverter-defibrillator-induced localized constrictive
      pericarditis.
AB  - In the 1990s, epicardial implantable cardioverter-defibrillator (ICD) patches
      were frequently implanted to treat life-threatening ventricular arrhythmia.
      However, owing to the high rates of functional failure, the patch system has been
      replaced by transvenous ICD leads system. Although morphological abnormalities
      such as dense fibrosis around the patch are quite frequent, epicardial ICD patch
      induced localized constrictive pericarditis is very rare. We encountered a
      patient who had severe heart failure due to constrictive pericarditis, 23 years
      after the implantation of epicardial ICD patches. The heart failure was treated
      after complete resection of the patches and dense fibrosis on the surface of both
      the right and the left ventricles. To our knowledge, this is the first report on
      the treatment of epicardial ICD patch-induced localized constrictive
      pericarditis.

PMID- 29049637
TI  - Multiple Hyperpigmented Macules in a Child.

PMID- 29049638
TI  - Blood Transfusions From Previously Pregnant Women and Mortality: Interpreting the
      Evidence.

PMID- 29049639
TI  - Oral Hypoglycemic Agents Added to Insulin Monotherapy for Type 2 Diabetes.
AB  - Clinical Question: Among patients with type 2 diabetes mellitus who do not
      achieve optimal glycemic control with insulin monotherapy, is the addition of
      oral hypoglycemic agents associated with benefits (measured by lowering of
      hemoglobin A1c) or adverse effects? Bottom Line: Adding a sulfonylurea to insulin
      was associated with more hypoglycemic events compared with insulin alone, but
      this association was not observed for metformin. Adding a sulfonylurea or
      metformin to insulin was associated with a decrease in hemoglobin A1c of
      approximately 1.0%.

PMID- 29049640
TI  - Leukemia Drug Makes a Comeback.

PMID- 29049641
TI  - Remote Control Mammography.

PMID- 29049642
TI  - Antibacterial Inhibits Resistance.

PMID- 29049644
TI  - Cursus Honorum, Or How to Get Ahead in the Medical World.

PMID- 29049645
TI  - Acute Zika Virus Infection as a Risk Factor for Guillain-Barre Syndrome in Puerto
      Rico.

PMID- 29049646
TI  - Acupuncture for Infertility in Polycystic Ovary Syndrome.

PMID- 29049647
TI  - Acupuncture for Infertility in Polycystic Ovary Syndrome.

PMID- 29049648
TI  - Acupuncture and Sham Acupuncture for Pain Relief.

PMID- 29049649
TI  - Acupuncture for Stress Urinary Incontinence.

PMID- 29049650
TI  - Acupuncture for Infertility in Polycystic Ovary Syndrome-Reply.

PMID- 29049651
TI  - Acupuncture and Sham Acupuncture for Pain Relief-Reply.

PMID- 29049652
TI  - Acupuncture for Stress Urinary Incontinence-Reply.

PMID- 29049653
TI  - Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on
      Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial.
AB  - Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective
      therapies for the treatment of type 2 diabetes and are all currently available as
      an injection. Objectives: To compare the effects of oral semaglutide with placebo
      (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control
      in patients with type 2 diabetes. Design, Setting, and Patients: Phase 2,
      randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up
      at 100 sites (hospital clinics, general practices, and clinical research centers)
      in 14 countries conducted between December 2013 and December 2014. Of 1106
      participants assessed, 632 with type 2 diabetes and insufficient glycemic control
      using diet and exercise alone or a stable dose of metformin were randomized.
      Randomization was stratified by metformin use. Interventions: Once-daily oral
      semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40
      mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose
      escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast
      escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly
      subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. Main Outcomes and
      Measures: The primary end point was change in hemoglobin A1c (HbA1c) from
      baseline to week 26. Secondary end points included change from baseline in body
      weight and adverse events. Results: Baseline characteristics were comparable
      across treatment groups. Of the 632 randomized patients (mean age, 57.1 years
      [SD, 10.6]; men, 395 (62.7%); diabetes duration, 6.3 years [SD, 5.2]; body
      weight, 92.3 kg [SD, 16.8]; BMI, 31.7 [SD, 4.3]), 583 (92%) completed the trial.
      Mean change in HbA1c level from baseline to week 26 decreased with oral
      semaglutide (dosage-dependent range, -0.7% to -1.9%) and subcutaneous semaglutide
      (-1.9%) and placebo (-0.3%); oral semaglutide reductions were significant vs
      placebo (dosage-dependent estimated treatment difference [ETD] range for oral
      semaglutide vs placebo, -0.4% to -1.6%; P = .01 for 2.5 mg, <.001 for all other
      dosages). Reductions in body weight were greater with oral semaglutide (dosage
      dependent range, -2.1 kg to -6.9 kg) and subcutaneous semaglutide (-6.4 kg) vs
      placebo (-1.2 kg), and significant for oral semaglutide dosages of 10 mg or more
      vs placebo (dosage-dependent ETD range, -0.9 to -5.7 kg; P < .001). Adverse
      events were reported by 63% to 86% (371 of 490 patients) in the oral semaglutide
      groups, 81% (56 of 69 patients) in the subcutaneous semaglutide group, and 68%
      (48 of 71 patients) in the placebo group; mild to moderate gastrointestinal
      events were most common. Conclusions and Relevance: Among patients with type 2
      diabetes, oral semaglutide resulted in better glycemic control than placebo over
      26 weeks. These findings support phase 3 studies to assess longer-term and
      clinical outcomes, as well as safety. Trial Registration: clinicaltrials.gov
      Identifier: NCT01923181.

PMID- 29049655
TI  - Risks of Codeine and Tramadol in Children.

PMID- 29049654
TI  - Association of Blood Transfusion From Female Donors With and Without a History of
      Pregnancy With Mortality Among Male and Female Transfusion Recipients.
AB  - Importance: Transfusion of red blood cells from female donors has been associated
      with increased mortality in male recipients. Objective: To quantify the
      association between red blood cell transfusion from female donors with and
      without a history of pregnancy and mortality of red blood cell recipients.
      Design, Setting, and Participants: Retrospective cohort study of first-time
      transfusion recipients at 6 major Dutch hospitals enrolled from May 30, 2005, to
      September 1, 2015; the final follow-up date was September 1, 2015. The primary
      analysis was the no-donor-mixture cohort (ie, either all red blood cell
      transfusions exclusively from male donors, or all exclusively from female donors
      without a history of pregnancy, or all exclusively from female donors with a
      history of pregnancy). The association between mortality and exposure to
      transfusions from ever-pregnant or never-pregnant female donors was analyzed
      using life tables and time-varying Cox proportional hazards models. Exposures:
      Red blood cell transfusions from ever-pregnant or never-pregnant female donors,
      compared with red blood cell transfusions from male donors. Main Outcomes and
      Measures: All-cause mortality during follow-up. Results: The cohort for the
      primary analyses consisted of 31 118 patients (median age, 65 [interquartile
      range, 42-77] years; 52% female) who received 59 320 red blood cell transfusions
      exclusively from 1 of 3 types of donors (88% male; 6% ever-pregnant female; and
      6% never-pregnant female). The number of deaths in this cohort was 3969 (13%
      mortality). For male recipients of red blood cell transfusions, all-cause
      mortality rates after a red blood cell transfusion from an ever-pregnant female
      donor vs male donor were 101 vs 80 deaths per 1000 person-years (time-dependent
      "per transfusion" hazard ratio [HR] for death, 1.13 [95% CI, 1.01-1.26]). For
      receipt of transfusion from a never-pregnant female donor vs male donor,
      mortality rates were 78 vs 80 deaths per 1000 person-years (HR, 0.93 [95% CI,
      0.81-1.06]). Among female recipients of red blood cell transfusions, mortality
      rates for an ever-pregnant female donor vs male donor were 74 vs 62 per 1000
      person-years (HR, 0.99 [95% CI, 0.87 to 1.13]); for a never-pregnant female donor
      vs male donor, mortality rates were 74 vs 62 per 1000 person-years (HR, 1.01 [95%
      CI, 0.88-1.15]). Conclusions and Relevance: Among patients who received red blood
      cell transfusions, receipt of a transfusion from an ever-pregnant female donor,
      compared with a male donor, was associated with increased all-cause mortality
      among male recipients but not among female recipients. Transfusions from never
      pregnant female donors were not associated with increased mortality among male or
      female recipients. Further research is needed to replicate these findings,
      determine their clinical significance, and identify the underlying mechanism.

PMID- 29049657
TI  - Better.

PMID- 29049659
TI  - Adverse Outcomes of Reducing Foreign Aid for HIV Programs.

PMID- 29049660
TI  - Mental Health Burden Increasing in Eastern Mediterranean Region.

PMID- 29049661
TI  - Corruption Poses Critical Challenge to Global Health Efforts.

PMID- 29049663
TI  - Surgical treatment of left ventricular echinococcosis through the HeartPort
      technique.
AB  - Echinococcal lesions rarely involve the heart; nonetheless, echinococcal cysts of
      the left ventricular myocardium often demand surgical treatment due to the risk
      of rupture and anaphylaxis. Herein, an echinococcal cyst of the anteroapical left
      ventricular wall was managed through small left anterior thoracotomy; repair was
      achieved under cardioplegic arrest (endoaortic balloon occlusion) with an
      uneventful course. We discuss the usefulness of such a less invasive approach for
      the depicted lesion (minimized manipulation of the heart and reduced surgical
      aggressiveness) and for other lesions involving the apical/lateral LV region.

PMID- 29049662
TI  - Flexible mechanoprosthesis made from woven ultra-high-molecular-weight
      polyethylene fibres: proof of concept in a chronic sheep model.
AB  - OBJECTIVES: Ultra-high-molecular-weight polyethylene (UHMWPE) fibres are
      flexible, have high tensile strength, and platelet and bacterial adhesion is low.
      Therefore, UHMWPE may overcome limitations of current mechanical valves and
      bioprostheses. In this study, the biocompatibility and functionality of prototype
      handmade stented valves from woven UHMWPE (U-valve) was assessed in a chronic
      sheep model with acetylsalicylic acid monotherapy. METHODS: Native pulmonary
      valves of 23 sheep were replaced by U-valves (n = 18) or Perimount bovine
      bioprostheses (reference group, n = 5). Sheep received 80 mg of acetylsalicylic
      acid daily. Follow-up was conducted at 1 week (n = 4), 1 month (n = 5), 3 months
      (n = 5) and 6 months (n = 4) in the U-valve group and at 3 months (n = 2) and 6
      months (n = 3) in the reference group. Epicardial echocardiography and histology
      were used to assess valve function and tissue deposition, respectively. RESULTS:
      Seventeen U-valve sheep (94%) and 3 reference sheep (60%) survived the
      perioperative period. One reference valve sheep was sacrificed after 4 months
      because of congestive heart failure. At explantation, all U-valves were intact
      without leaflet tearing. Up to 3 months, U-valves were flexible and free of
      stenosis. Regurgitation was mostly mild though gradually increasing; histology
      showed minimal connective tissue near the leaflet base and sparse calcification.
      At 6 months, connective tissue was diffusely observed on the leaflets with
      retraction and consecutive regurgitation and leaflet thickening. CONCLUSIONS:
      Valves made from UHMWPE fibres demonstrated early feasibility in the pulmonary
      valve position with reasonably good haemodynamics and intact valve materials up
      to 6 months. Gradual leaflet thickening and retraction were observed after 3
      months due to connective tissue overgrowth.

PMID- 29049664
TI  - Acute Type I aortic dissection: a propensity-matched comparison of elephant trunk
      and arch debranching repairs.
AB  - OBJECTIVES: Our goal was to compare the performance of the frozen elephant trunk
      (FET) and the hybrid aortic arch debranching procedures for acute Type I aortic
      dissection. METHODS: From January 2013 to December 2015, 168 patients with Type I
      aortic disease underwent ascending aorta and total aortic arch replacement with
      FET implantation (the FET group, n = 132) or arch debranching with 1-stage aortic
      arch exclusion using an endovascular stent in a retrograde manner (the
      debranching group, n = 36). A propensity score-matched subgroup of 26 pairs was
      identified. Perioperative data and mid-term follow-up results were assessed.
      RESULTS: In the FET and the debranching groups, the 30-day mortality rates were
      14.4% and 5.6% (P = 0.254) and the incidence of stroke was 5.3% and 5.6% (P >
      0.999). Cardiopulmonary bypass time was significantly shortened, and the
      circulatory arrest was exempted in the debranching group. Cardiopulmonary bypass
      time was identified as a predictor for 30-day mortality (P = 0.027, odds ratio
      1.01). Body mass index >= 25 kg/m2 was associated with multiorgan dysfunction
      syndrome (P = 0.016, odds ratio 3.51). Surgical modality did not significantly
      affect early outcomes. The 3-year survival rate was 76.1% (95% confidence
      interval, 63.0-81.9%) in the FET group and 82.5% (95% confidence interval, 65.2
      91.8%) in the debranching group (P = 0.330). CONCLUSIONS: The hybrid aortic arch
      procedure without circulatory arrest can be safely performed on patients with
      acute Type I aortic dissection. Irrespective of cost-effectiveness, arch
      debranching was a promising alternative for patients who were unfit for the FET
      procedure.

PMID- 29049665
TI  - Reoperation for mitral paravalvular leak: a single-centre experience with 200
      patients.
AB  - OBJECTIVES: Paravalvular leak (PVL) is a major cause of morbidity and mortality
      after mitral valve replacement. Risk factors and data on long-term surgical
      outcomes are lacking. METHODS: Between January 1995 and December 2012, 206 [118
      males (57%)] patients underwent reoperation due to mitral PVL. Mean age was 64 +/
      11 years. Haemolytic anaemia was present in 85 (41%) patients, while 137 (67%)
      patients were in New York Heart Association Class III or IV. Baseline creatinine
      was above 1.5 in 91 (44%) patients, while chronic steroids were used in 14 (7%)
      patients. Active endocarditis was present in 8 (4%) patients. Device occlusion
      was attempted in 21 (10%) patients. RESULTS: PVL was most common at the
      aortomitral curtain (82 patients, 40%). Repair was possible in 105 (51%)
      patients. Early mortality occurred in 11 (5%) patients. Mean follow-up was 5
      (maximum 19) years. Overall survival at 1, 5 and 15 years was 83%, 62% and 16%,
      respectively. Death due to heart failure or cardiogenic shock occurred in 39
      patients. Recurrence occurred in 43 (21%) patients and reoperation was required
      in 19 patients. Multivariate analysis revealed advanced New York Heart
      Association class (P < 0.0001), active endocarditis (P = 0.013), chronic steroids
      (P = 0.022), previous coronary artery bypass grafting (P = 0.026), baseline
      creatinine above 1.5 (P = 0.001), postoperative need for dialysis (P = 0.036) and
      residual PVL (P < 0.0001) to be predictors of late mortality. Active endocarditis
      (P = 0.0004) and chronic steroids (P = 0.002) were significant predictors for PVL
      recurrence. Freedom from reoperation due to PVL recurrence was 89% and 84%, while
      freedom from late intervention was 94% and 61% at 5 and 15 years, respectively.
      CONCLUSIONS: PVL after mitral valve replacement is associated with increased
      morbidity and mortality. Re-repair is possible, but recurrent PVL is a risk
      factor for late mortality, and reoperation should be performed prior to the onset
      of advanced heart failure.

PMID- 29049667
TI  - When can computed tomography-fissure analysis replace Chartis collateral
      ventilation assessment in the prediction of patients with emphysema who might
      benefit from endobronchial valve therapy?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was when can computed tomography-fissure
      analysis replace Chartis collateral ventilation assessment in the prediction of
      patients with emphysema who might benefit from endobronchial valve therapy?
      Twelve papers were chosen to answer the question. The authors, date, journal,
      country of publication and study type; patient group studied; relevant outcomes
      and results of these papers were tabulated. Five studies retrospectively compared
      the prognostic value of 2 methods. They found that when computed tomography
      fissure analysis showed an intact fissure more than 95%, both methods were
      equivalent in correctly predicting a positive response to valve therapy.
      Concordant results were found in two-thirds of patients, and the additional
      evaluation with Chartis did not confer a significant advantage. Yet the
      increasing cost and time to procedure, the different ranges of Chartis findings
      patterns not correlated with lung volume reduction and the unfeasibility of the
      measurements (reported in 6-17% of the most series) due to difficult anatomy are
      additional limitations for its use. Conversely, in patients with fissure
      integrity between 75% and 90%, Chartis assessment could improve the patient
      selection, because the computed tomography-fissure analysis alone is unable to
      predict a successful treatment. In this situation, Chartis had a 31% ability to
      predict those patients who can be successfully treated. In BeLieVer-HIfi Study,
      post hoc analysis revealed that the additional use of Chartis for patient
      selection significantly improved outcomes. Similarly, STELVIO, LIVE and IMPACT
      studies, where only patients with complete fissure and negative Chartis
      measurement were treated, showed significant benefits after valve treatment.
      Finally, in patients with fissure integrity below 75%, the negative predictive
      value for lobar atelectasis is 100%. Thus, in these patients, it could be futile
      even considering a Chartis assessment.

PMID- 29049666
TI  - Bivalirudin anticoagulation for left ventricular assist device implantation on an
      extracorporeal life support system in patients with heparin-induced
      thrombocytopenia antibodies.
AB  - OBJECTIVES: Heparin-induced thrombocytopenia (HIT) requires alternative
      anticoagulation strategies. We investigated outcomes in patients with HIT
      antibodies undergoing low-dose bivalirudin anticoagulation during left
      ventricular assist device implantation on an extracorporeal life support system
      (ECLS) and compared the results with non-HIT patients treated with heparin and
      receiving left ventricular assist device implantation with ECLS support. METHODS:
      The institutional ventricular assist device database was searched for the period
      from March 2012 to March 2016. The primary end-point was the need for early (<7
      days) surgical re-exploration due to persistent haemorrhage or cardiac tamponade
      postoperatively. The secondary clinical end-points were delayed chest closure,
      stroke, intracranial bleeding, re-thoracotomy >7 days and mortality up to 1 year.
      Unadjusted comparison was used for the entire groups. Because of non-random group
      assignment, propensity score matching was also performed to compare treatment
      effects. RESULTS: Twenty-one patients were treated with bivalirudin and 36
      patients with heparin. INTERMACS levels were lower, inotropic score was higher
      and the prevalence of mechanical ventilation and preoperative ECLS implants was
      also significantly higher in the heparin group than in the bivalirudin group (P
      values <0.05). The primary end-point was reached by 19% in the bivalirudin group
      and 16.7% in the heparin group (bivalirudin group: odds ratio 1.18, 95%
      confidence interval 0.29-4.76; P = 0.820). The propensity score-matched groups
      also showed no difference in this regard (P = 0.455). All secondary clinical end
      points were comparable between groups, both in the unadjusted analysis and in the
      propensity score-matched groups. CONCLUSIONS: In patients with HIT antibodies,
      low-dose bivalirudin anticoagulation on ECLS support appears to be a feasible
      option for left ventricular assist device implantation.

PMID- 29049669
TI  - Complementary and Alternative Medicine in Cancer Care.

PMID- 29049668
TI  - One-stage definitive repair of complete atrioventricular septal defect and
      pulmonary atresia with major aortopulmonary collateral arteries.
AB  - Pulmonary atresia with ventricular septal defect and major aortopulmonary
      collateral arteries is considered the most severe end of the tetralogy of Fallot
      spectrum, whereas complete atrioventricular septal defect associated with
      tetralogy of Fallot is a rare congenital defect. However, the combination of
      pulmonary atresia, major aortopulmonary collateral artery and complete
      atrioventricular septal defect is extremely rare, and surgical repair has not
      been reported. We describe a successful, 1-stage correction in a 7-month-old boy
      with this condition, who had an additional complication of a single aortic outlet
      from the right ventricle and significant atrioventricular valve regurgitation.

PMID- 29049670
TI  - An Alternative Method to Characterize the Quasi-Static, Nonlinear Material
      Properties of Murine Articular Cartilage.
AB  - With the onset and progression of osteoarthritis (OA), articular cartilage (AC)
      mechanical properties are altered. These alterations can serve as an objective
      measure of tissue degradation. Although the mouse is a common and useful animal
      model for studying OA, it is extremely challenging to measure the mechanical
      properties of murine AC due to its small size (thickness < 50 MUm). In this
      study, we developed novel and direct approach to independently quantify two quasi
      static mechanical properties of mouse AC: the load-dependent (nonlinear) solid
      matrix Young's modulus (E) and drained Poisson's ratio (nu). The technique
      involves confocal microscope-based multiaxial strain mapping of compressed,
      intact murine AC followed by inverse finite element analysis (iFEA) to determine
      E and nu. Importantly, this approach yields estimates of E and nu that are
      independent of the initial guesses used for iterative optimization. As a proof of
      concept, mechanical properties of AC on the medial femoral condyles of wild-type
      mice were obtained for both trypsin-treated and control specimens. After
      proteolytic tissue degradation induced through trypsin treatment, a dramatic
      decrease in E was observed (compared to controls) at each of the three tested
      loading conditions. A significant decrease in nu due to trypsin digestion was
      also detected. These data indicate that the method developed in this study may
      serve as a valuable tool for comparative studies evaluating factors involved in
      OA pathogenesis using experimentally induced mouse OA models.

PMID- 29049671
TI  - Application of a Discrete Choice Experiment to Assess Adherence-Related
      Motivation Among Adolescents and Young Adults With Cancer.
AB  - Objective: To develop and pilot test a discrete choice experiment (DCE) to assess
      the specific factors likely to motivate a given adolescent or young adult with
      cancer to adhere to medications included in treatment protocols. Methods: A
      multimethod and iterative approach was used. Twenty adolescents and young adults
      with cancer participated in DCE pilot testing and refinement. Hierarchical Bayes
      was used to estimate attribute and attribute-level preference scores for each
      participant. Results: The final DCE included nine choice sets composed of four
      attributes. The resulting DCE was modified with feedback from 20 adolescents and
      young adults (M[SD] age = 18.66 [2.95]) with cancer. The DCE was understandable
      and relevant. The factors likely to motivate adolescents and young adults with
      cancer to be adherent differed across individuals. Conclusions: DCEs including
      the measure developed in this manuscript offer a novel approach to understanding
      individual-level differences critical for informing adherence-promotion efforts.

PMID- 29049672
TI  - High mortality in patients with tracheoarterial fistulas: clinical experience and
      treatment recommendations.
AB  - OBJECTIVES: A tracheoarterial fistula (TAF) is an uncommon but a critical
      complication of tracheostomy and represents a surgical emergency. Surgical
      therapy with ligation of the brachiocephalic trunk can be considered as the first
      choice of treatment to control massive and life-threatening haemorrhage. METHODS:
      We describe 3 cases of TAF in patients who had long-term placement of a
      tracheostomy tube and the occurrence of a severe massive haemorrhage caused by an
      injured brachiocephalic trunk. All cases required emergent surgical revision.
      Different surgical techniques were used. In addition to the 3 case reports, we
      present a review of the literature of published TAF cases, summarize the
      different measures to control bleeding and compare the operative procedures used
      in the treatment of TAF. RESULTS: The occurrence of TAF is rare and constitutes a
      surgical emergency. The mortality rate of tracheoarterial erosion is 100% without
      surgical intervention for active bleeding into the airway. Therefore, rapid
      control of bleeding (via digital compression and an overinflated cuff) is the
      most important and first step of therapy. Subsequent emergency surgery with
      ligation and resection of the TAF and covering of the trachea should be
      considered to finally control the massive haemorrhage. In addition,
      cardiopulmonary bypass and circulatory arrest can be useful for surgical
      treatment of cases with uncontrollable bleeding. CONCLUSIONS: The mortality rate
      after resection of the fistula remains high. Finally, the most important factors
      for patient survival and outcomes are quick diagnosis of the TAF and immediate
      surgical control of bleeding.

PMID- 29049673
TI  - Incidence and echocardiographic predictors of early postoperative right
      ventricular dysfunction following left ventricular assist implantation in
      paediatric patients.
AB  - OBJECTIVES: Left ventricular assist device implantation is an established therapy
      for paediatric patients with end-stage heart failure. Early right ventricular
      dysfunction (RVD) after implantation still remains a challenge in the
      postoperative period. This study sought to determine the incidence of RVD and to
      identify echocardiographic predictors of RVD in paediatric patients, as well
      describing associated clinical outcome. METHODS: Prospectively collected
      preoperative echocardiographic, haemodynamic, demographic and biochemical data
      from 48 patients scheduled for left ventricular assist device implantation were
      evaluated. Incidence of high central venous pressure, decreased central venous
      saturation, high inotropic support requirements or need for mechanical support of
      the right ventricle during the first 48 h after implantation were used to define
      RVD. Echocardiographic assessments of right ventricular geometry, function using
      linear dimensions, areas and tricuspid annular plane systolic excursion (TAPSE)
      were performed preoperatively and the relative relationships between these
      parameters were evaluated. RESULTS: We included 48 consecutive paediatric
      patients (median age 5 years, range 0-17; median weight 15.9 kg, range 3.6-91).
      According to our criteria, 24 (50%) patients developed RVD. TAPSE as the
      parameter for assessment of longitudinal systolic function was significantly
      lower in this group (P = 0.01). The difference became even more pronounced after
      normalization to the RV end-diastolic diameter in long axis with P = 0.003. The
      odds ratio for patients with TAPSE/RV end-diastolic diameter in long axis <17.1%
      to develop RVD was 7.7 (P = 0.002). CONCLUSIONS: RVD occurs frequently in
      paediatric patients after left ventricular assist device. TAPSE, normalized to
      the RV end-diastolic diameter, may help to identify patients at risk for RVD. The
      predictive value of this parameter supports decision making to plan for adequate
      pharmacological support or consider early upgrading to mechanical RV support.

PMID- 29049674
TI  - Collaboration Between ACGME and AOA Programs to Enhance Success in the Single
      Accreditation System: A Process Paper.
AB  - Beginning in 2020, all residency programs will be accredited by the Accreditation
      Council for Graduate Medical Education (ACGME). Programs accredited by the
      American Osteopathic Association (AOA) that do not achieve ACGME pre
      accreditation status by 2020 will be forced to close, resulting in loss of
      graduate medical education slots and affecting the physician workforce locally
      and nationally. Current ACGME programs are in a position to help consult,
      support, and learn from local AOA-only programs as they work toward meeting ACGME
      accreditation requirements, but to date there have been only limited
      collaborations. A regional network of ACGME- and dually accredited family
      medicine residency programs ("the Network") and family medicine programs solely
      accredited by the AOA recognized the imperative to support the AOA-only programs
      with their accreditation transitions to preserve their primary care residency
      positions. This article describes the inputs, activities, outputs, and outcomes
      of these collaborative efforts to establish communications and strategies using a
      logic model program "road map" format. Initial efforts included a collaborative
      conference and ongoing consultations and workshops. This model can be replicated
      for program collaborations in other locations.

PMID- 29049675
TI  - Combined perventricular septal defect closure and patent ductus arteriosus
      ligation via the lower ministernotomy approach.
AB  - Over the past decade, minimally invasive approaches have been advocated for
      surgical correction of congenital defects to reduce costs related to
      hospitalization and for improved cosmesis. Minimal skin incisions and partial
      sternotomy reduce surgical trauma, however these techniques might not be
      successful in treating a number of congenital pathological conditions,
      particularly for combined congenital defects. We focused on cases with a combined
      presentation of ventricular septal defect and patent ductus arteriosus. We
      studied 12 infants who successfully underwent surgical treatment for a combined
      single-stage ventricular septal defect and patent ductus arteriosus closure
      through a lower ministernotomy without using cardiopulmonary bypass and X-rays.
      No intraoperative and early postoperative complications or mortality were noted.
      Postoperative echocardiography did not reveal residual shunts. The proposed
      technique is safe and reproducible in infants.

PMID- 29049676
TI  - Cholesterol Crystals Secondary to Coats-Like Response With Retinitis Pigmentosa.

PMID- 29049677
TI  - Sveinsson Chorioretinal Atrophy: Helicoid Peripapillary Chorioretinal
      Degeneration.

PMID- 29049678
TI  - Limbal Dermoid in a Teenage Boy.

PMID- 29049679
TI  - Fungal Keratitis After Boston Keratoprosthesis.

PMID- 29049682
TI  - Brain Metastases in Lung Cancer With Targetable Mutations-Reply.

PMID- 29049683
TI  - Ventricular assist device in a failing total cavopulmonary connection: a new step
      by-step approach.
AB  - The management of failing Fontan patients with mechanical circulatory support has
      been reported with unsatisfactory results. A 5-year-old girl, listed for heart
      transplantation for failing Fontan, underwent rescue extracorporeal membrane
      oxygenation support. As it was necessary to move the patient to the Berlin Heart
      Excor, a step-by-step approach was designed to obtain a gradual adaptation to
      this form of support. A central extracorporeal membrane oxygenation, with a
      Berlin Heart apical and aortic cannulae, was implanted leaving the previously
      positioned femoral vein cannula in parallel with the outflow apical one. The
      femoral vein cannula was removed when the lungs recovered from the effects of
      surgical trauma. Four days later, the Fontan fenestration was closed, and after 4
      more days, a gradual reduction of gas support was planned without problems.
      Oxygenator was then removed, and 4 days later, a 30-ml Berlin Heart EXCOR
      ventricle replaced the centrifugal pump. This sequential approach, which has
      never been described before, can improve the results of the ventricular assist
      device support in failing Fontan patients, because it allows a gradual
      adaptation, even in patients with damaged lungs.

PMID- 29049684
TI  - Coagulation profile in open and video-assisted thoracoscopic lobectomies: a
      cohort study.
AB  - OBJECTIVES: Lung cancer patients are perceived to have a relatively high risk of
      venous thromboembolic events due to an activation of the coagulation system. In
      terms of activation of the coagulation system, the difference between video
      assisted thoracoscopic surgery (VATS) and open lobectomies for primary lung
      cancer has not been investigated. The aim of this study was to compare the impact
      on the coagulation system in patients undergoing curative surgery for primary
      lung cancer by either VATS or open lobectomies. METHODS: In total, 62 patients
      diagnosed with primary lung cancer were allocated to either VATS (n = 32) or open
      lobectomies (n = 30). All patients received subcutaneous injections with
      dalteparin (Fragmin(r)) 5000 IE once daily. The coagulation was assessed pre- and
      intraoperatively, and the first 2 days postoperatively by standard coagulation
      blood tests, thromboelastometry (ROTEM(r)) and thrombin generation. RESULTS: The
      open lobectomies bled more than the VATS group and had a significantly lower
      platelet count (109/l) on postoperative Days 1 and 2 (198 vs 231 and 194 vs 243,
      respectively). The open group also had a higher international normalized ratio on
      postoperative Days 1 and 2 compared with the VATS group (1.21 vs 1.14 and 1.17 vs
      1.09, respectively). There were no differences in thromboelastometry (ROTEM(r))
      and thrombin generation parameters. None of the included patients developed
      venous thromboembolic events. CONCLUSIONS: In patients undergoing curative
      surgery for early-stage primary lung cancer, we observed a statistical non
      significant difference and a similar-sized minor impact on the coagulation
      system.

PMID- 29049685
TI  - Endothelin-1 is associated with dilatation of the left atrium and can be an
      independent predictor of atrial fibrillation after mitral valve surgery.
AB  - OBJECTIVES: This study analysed the association between endothelin-1 (ET-1) and
      left atrial dimension (LAD) and evaluated whether ET-1 can be a predictor of
      postoperative atrial fibrillation (POAF) after mitral valve surgery. METHODS:
      This is a prospective study that enrolled 80 patients who underwent isolated
      mitral valve surgery. Plasma concentrations of ET-1 from peripheral venous blood
      were tested. POAF was detected using a telemetry strip or 12-lead
      electrocardiogram until the time of discharge. RESULTS: Patients undergoing
      mitral valve surgery with preoperative sinus rhythm (n = 80; average age 63.9 +/-
      7.9 years) were recruited to this study. POAF was documented in 31 (38.8%)
      patients. Preoperative plasma ET-1 levels were higher in patients with POAF
      compared to those without POAF (2.23 +/- 0.67 vs 1.68 +/- 0.59 pg/ml; P < 0.001).
      The plasma concentrations of ET-1 were positively correlated with LAD (Pearson's
      r = 0.421; P < 0.001). Multivariate logistic regression analysis revealed that
      LAD (odds ratio 1.170, 95% confidence interval 1.039-1.317; P = 0.009) and
      preoperative plasma ET-1 levels (upper versus lower 50th percentile: odds ratio
      3.713, 95% confidence interval 1.085-12.701; P = 0.037) were predictors of POAF
      after mitral valve surgery. CONCLUSIONS: Plasma levels of ET-1 were positively
      correlated with LAD in patients with mitral valve disease. An elevated
      preoperative plasma ET-1 level can be used as a predictor of POAF after mitral
      valve surgery.

PMID- 29049687
TI  - The Health Care Professional's Pledge: Protecting Our Patients From Firearm
      Injury.

PMID- 29049686
TI  - National practice variation in pneumonectomy perioperative care among Canadian
      thoracic surgeons.
AB  - OBJECTIVES: Our objective was to assess perioperative pneumonectomy practices
      among Canadian thoracic surgeons as part of a quality-improvement initiative to
      determine practice variability and identify areas for study/improvement. METHODS:
      After several rounds of survey development and piloting, a 29-item survey was
      distributed using the Dillman method to all practicing members of the Canadian
      Association of Thoracic Surgeons. RESULTS: The response rate was 87% (62 of 71).
      Median number of pneumonectomies performed annually was 3.5 (interquartile range
      2.75-5.00). Routine preoperative workup was variable, but the most consistently
      reported tests were diffusing capacity of the lungs for carbon monoxide (87%, n =
      54) and spirometry (85%, n = 53). Reported routine use of epidurals (84%, n = 52)
      was more prevalent than paravertebral blocks (18%, n = 11). Many (69%, n = 43)
      reported intraoperative restriction <2 l. Postoperatively, 84% (n = 52) reported
      daily fluid restriction <2 l. Regarding intraoperative protective ventilation
      strategies, respondents appeared more focused on minimizing peak airway pressures
      (55%, n = 34) rather than tidal volumes (18%, n = 11). Twenty-four percent (n =
      15) reported using intraoperative steroids in attempts to decrease postoperative
      complications. Thirty-two percent (n = 20) do not routinely insert chest tubes,
      whereas the most common practice (44%, n = 27) was to insert chest tubes attached
      to conventional drainage systems without suction. Eighty-two percent (n = 52)
      reported willingness to participate in multicentre studies regarding
      perioperative pneumonectomy practices. CONCLUSIONS: Our findings suggest
      significant variability in reported preoperative, intraoperative and
      postoperative care practices for pneumonectomy across Canada. This survey has a
      high response rate, representing the Canadian experience, and highlights several
      areas for study and quality-improvement initiatives. Many respondents report
      willingness to participate in multicentre initiatives.

PMID- 29049688
TI  - Risk of de novo dialysis after elective cardiac surgery according to preoperative
      renal dysfunction.
AB  - OBJECTIVES: The aim was to estimate the risk of dialysis postoperative de novo
      dialysis in patients undergoing elective cardiac surgery, according to varying
      degrees of pre-existing renal dysfunction, and to compare the outcomes with the
      expected prevalence of dialysis based on several risk scores. METHODS: A
      retrospective analysis was performed over a 5-year period (2012-16) from a series
      of 1332 adult patients who underwent elective cardiac surgery. Patients were
      divided into 3 estimated creatinine clearance (eCrCl) groups: eCrCl >60 ml/min,
      eCrCl from 50 ml/min to 60 ml/min and eCrCl <=49 ml/min. The primary outcome was
      any renal failure requiring first-time dialysis during the postoperative hospital
      stay. The expected risk for postoperative dialysis was calculated with 3
      predictive scores: the Society of Thoracic Surgeons Bedside Risk Tool, the
      Cleveland Clinic Score and the Simplified Renal Index. The global accuracy of
      eCrCl and the different scores was evaluated in terms of calibration and
      discrimination. RESULTS: In the overall population, 26.6% of patients presented
      moderate or severe pre-existing renal dysfunction, and the need for de novo
      dialysis varied from 0.6% to 5.0% depending on the degree of preoperative eCrCl
      (P < 0.0001). Preoperative renal dysfunction with eCrCl <50 ml/min was associated
      with nearly 8-fold increase of risk for postoperative dialysis; eCrCl between 50
      ml/min and 60 ml/min showed a 2-fold increase, though this last difference did
      not reach statistical significance. CONCLUSIONS: In elective cardiac surgery,
      isolated preoperative eCrCl seemed to be an accurate indicator of risk for
      postoperative de novo dialysis. More complex models did not provide additional
      information to stratify that risk.

PMID- 29049689
TI  - A Nonlinear Viscoelastic Model for Adipose Tissue Representing Tissue Response at
      a Wide Range of Strain Rates and High Strain Levels.
AB  - Finite element human body models (FEHBMs) are nowadays commonly used to simulate
      pre- and in-crash occupant response in order to develop advanced safety systems.
      In this study, a biofidelic model for adipose tissue is developed for this
      application. It is a nonlinear viscoelastic model based on the Reese et al.'s
      formulation. The model is formulated in a large strain framework and applied for
      finite element (FE) simulation of two types of experiments: rheological
      experiments and ramped-displacement experiments. The adipose tissue behavior in
      both experiments is represented well by this model. It indicates the capability
      of the model to be used in large deformation and wide range of strain rates for
      application in human body models.

PMID- 29049690
TI  - Surgical treatment of postinfarction ventricular septal defect: risk factors and
      outcome analysis.
AB  - OBJECTIVES: Postinfarction ventricular septal defect is a serious mechanical
      complication of acute myocardial infarction associated with high postoperative
      mortality. The aim of this study was to review our experience with surgical
      repair of postinfarction ventricular septal defect and to identify predictors of
      early and late outcomes. METHODS: Thirty-nine patients (19 men and 20 women, mean
      age 68.4 +/- 9.9 years) with postinfarction ventricular septal defect who
      underwent surgical repair at our institution between 1996 and 2016 were
      retrospectively evaluated. Risk factors were assessed by univariate analysis,
      with those found significant included in multivariate analysis. RESULTS: The
      ventricular septal defect was anterior in 21 (54%) patients and posterior in 18
      (46%) patients. Mean aortic cross-clamp time was 91.8 +/- 26.8 min, and mean
      cardiopulmonary bypass time was 146.3 +/- 49.7 min. Twelve (31%) patients
      underwent concomitant coronary artery bypass grafting. The 30-day mortality rate
      was 36% (n = 14). The 30-day survival rate was higher with than without
      concomitant coronary artery bypass grafting (83% vs 56%), but concomitant
      coronary artery bypass grafting did not influence late survival (P = 0.098).
      Univariate analysis identified age, emergency surgery, inotropic support, Killip
      class, preoperative aspartate aminotransferase concentration, renal replacement
      therapy and ventricular septal defect diagnosis to operation interval as
      predictors of 30-day mortality. However, multivariate analysis showed that age
      and renal replacement therapy were the only independent risk factors of 30-day
      mortality. CONCLUSIONS: Surgical repair of postinfarction ventricular septal
      defect has a high 30-day mortality rate. Higher age at presentation and
      postoperative renal replacement therapy are independent predictors of early
      mortality.

PMID- 29049691
TI  - The advanced lung cancer inflammation index is an independent prognostic factor
      after surgical resection in patients with non-small-cell lung cancer.
AB  - OBJECTIVES: The usefulness of a recently developed advanced lung cancer
      inflammation index (ALI) has been reported in advanced non-small-cell lung cancer
      (NSCLC) and small-cell lung cancer. However, no previous studies have examined
      the prognostic significance of ALI in patients with operable NSCLC. Therefore,
      the aim of this study was to explore the relationship between ALI and the
      prognosis of resected NSCLC. METHODS: Three hundred and forty-three patients with
      NSCLC who underwent surgery at our institution between 2008 and 2012 were
      included. The ALI score was calculated as body mass index * serum
      albumin/neutrophil to lymphocyte ratio. A Web-based software programme [Cutoff
      Finder (http://molpath.charite.de/cutoff/)] was used to determine the optimal cut
      off value for ALI. The Kaplan-Meier methods and a multivariable Cox proportional
      hazards model were used to evaluate the potential prognostic factors. RESULTS:
      The optimal cut-off value of ALI was defined as 37.66. The low-ALI group (ALI <
      37.66) displayed more adverse clinical characteristics. Furthermore, compared
      with patients in the high-ALI group (ALI > 37.66), those in the low-ALI group had
      significantly poorer survival rates. On multivariable analysis, gender,
      histological diagnosis, pN status, serum carcinoembryonic antigen level, serum C
      reactive protein level and ALI were associated independently with cancer-specific
      survival. CONCLUSIONS: This study is the first to investigate whether ALI is
      useful for predicting postoperative survival in patients with NSCLC. Preoperative
      ALI might serve as a potentially clinically valuable marker of the prognosis for
      patients with operable NSCLC.

PMID- 29049692
TI  - Brain Metastases in Lung Cancer With Targetable Mutations: Should We Allow
      Targeted Treatment in Prognostic Indices?

PMID- 29049696
TI  - Heparin Side Effects-Reply.

PMID- 29049698
TI  - Acquired Immune Deficiency Syndrome-Reply.

PMID- 29049701
TI  - Effects of blood flow dynamics on autologous pericardial degeneration in
      reconstructed pulmonary arteries.
AB  - OBJECTIVES: To clarify the risk factors for abnormal degeneration of autologous
      pericardium, the mechanical stress on the endothelial tissue caused by turbulent
      blood flow in the pulmonary artery (PA) reconstructed with autologous pericardium
      and major aortopulmonary collateral arteries was assumed in pulmonary atresia and
      ventricular septal defect. METHODS: Patient-specific PA models were created for 6
      patients based on their past computed tomography images taken after
      unifocalization of major aortopulmonary collateral arteries. Computational fluid
      dynamics models were created to simulate the physiological pulsatile flow
      including the peripheral reflection wave, characteristic impedance and autonomous
      regulation system. Flow streamline, wall shear stress (WSS) and the oscillatory
      shear index (OSI) were calculated from the simulated result. PA degeneration was
      evaluated with the computed tomography images before the intracardiac repair.
      RESULTS: Regions with physiological high WSS had fewer abnormal changes.
      Excessively high WSS was often detected at the anastomosis site of the
      reconstructed PA, and intimal thickening was found in these regions during
      intracardiac repair. Regions with high OSI and low WSS had dilated change within
      several months. In 1 patient, in particular, detached vortex flow occurred at the
      rectangular angle anastomosis site of the right PA in flow streamline, resulting
      in high OSI and low WSS with abnormal enlargement in the pericardium.
      CONCLUSIONS: Endothelial stress caused by blood flow would affect the
      degeneration of autologous pericardium and major aortopulmonary collateral
      arteries in the reconstructed PA. High OSI and low WSS might induce enlargement
      or dilatation, and excessively high WSS in the anastomosis site might induce
      intimal thickening.

PMID- 29049702
TI  - Aortic root and hemiarch replacement in a patient with Loeys-Dietz and
      hypoplastic left heart syndromes.
AB  - A 15-year-old patient with hypoplastic left heart syndrome underwent 3-stage
      palliation by the age of 3 years. He was later diagnosed with Loeys-Dietz
      syndrome. On follow-up imaging, the neoaorta was dilated at 50 mm in diameter. He
      underwent aortic root replacement with a composite valve conduit and hemiarch
      replacement, using a boat-shaped Dacron graft. The uncertainty of how
      univentricular circulation would tolerate long bypass time steered us away from a
      total arch replacement. His postoperative recovery was uneventful. Imaging
      postoperatively demonstrated stable dilatation of the aorta distal to the
      hemiarch replacement. Considering the risk of reintervention, we elected to
      monitor the distal aorta. The combination of Loeys-Dietz syndrome and hypoplastic
      left heart syndrome presents unique challenges, rarely reported in the
      literature.

PMID- 29049703
TI  - Global Budgets for Safety-Net Hospitals.

PMID- 29049704
TI  - Mortality and morbidity of patients on the waiting list for coronary artery
      bypass graft surgery.
AB  - OBJECTIVES: The public health care system in Brazil has extensive waiting lists
      of patients requiring complex operations such as coronary artery bypass grafting
      (CABG). The purpose of this study was to identify the mortality and morbidity
      rates of the patients awaiting CABG and identify predictors of adverse events and
      their association with perioperative outcomes. METHODS: We conducted a
      retrospective analysis of outpatient medical records of patients referred for
      this elective procedure in Rio de Janeiro, Brazil. Excluded from the study were
      records of patients with any of the following: an indication for urgent surgery,
      unstable angina or concomitant surgical valvular disease or subsequent transfer
      to clinical or percutaneous therapy. RESULTS: A total of 274 patients were
      identified and met the inclusion criteria, with a median waiting time for an
      operation of 142.7 days. While waiting for CABG surgery, 31 (11.3%) patients died
      of any cause and 42 (15.3%) patients had a serious cardiac event (death,
      myocardial infarction or unstable angina). Of the 22 (8%) incidents of acute
      myocardial infarction, 8 (2.9%) were non-fatal and 14 (5.1%) were fatal. There
      was a greater risk of death awaiting CABG surgery in patients with a left
      ventricular ejection fraction below 45% (hazard ratio = 2.33, 95% confidence
      interval 1.02-5.32; P = 0.039). The operative mortality rate was 5.8%. Although
      there was no evidence of worse perioperative outcomes in patients with prolonged
      waiting times for an operation, there was an association between waiting more
      than 16 weeks for an operation and death while on the list. CONCLUSIONS:
      Extensive waiting periods for CABG contribute to higher mortality and morbidity
      rates, especially in patients with left ventricular dysfunction.

PMID- 29049705
TI  - Follow-up of a simple method for aortic valve reconstruction with fixed
      pericardium in children.
AB  - In 2013, we published a simple method for aortic valve reconstruction in children
      using fixed pericardium in this journal. This was not expected to be a durable
      solution but a temporizing measure in the absence of other solutions, in order to
      buy time for growth that would allow subsequent prosthetic valve insertion. As
      such, this was implemented in 3 patients with excellent immediate results, as
      reported in our original publication. We are now writing to provide longer term
      information. In 2 cases, a newborn and a 12-year-old boy, the valve calcified
      heavily at 4 years' follow-up. By then, the valvar annulus had grown sufficiently
      to accept a prosthetic valve in both cases. In these 2 cases, the material used
      for valve reconstruction was autologous pericardium fixed in 0.6% gluteraldehyde.
      In the third patient, a 3-year-old girl, the valve failed by dehiscence of the
      suture line 6 months following surgery. In this case, fixed bovine pericardium
      had been used, which is more rigid than autologous pericardium, thus possibly
      explaining the dehiscence. However, the pericardial patch was not calcified.
      Thus, the described method lived up to our expectation of buying time for growth
      for later insertion of a prosthetic valve in 2 of the 3 cases.

PMID- 29049706
TI  - Childhood ADHD Symptoms and Future Illicit Drug Use: The Role of Adolescent
      Cigarette Use.
AB  - Objectives: The aim of this study is to understand how early cigarette use might
      predict subsequent illicit drug use, especially among individuals with attention
      deficit hyperactivity disorder (ADHD) symptoms during childhood. Methods: Data
      were drawn from the National Longitudinal Study of Adolescent Health (Waves I
      IV). The analysis sample involves participants who had not used illicit drugs at
      Wave I, with no missing responses for studied predictors (N = 7,332). Results:
      Smoking status at Wave I (ever regular vs. never regular) and childhood ADHD
      symptoms predicted subsequent illicit drug use at Waves II to IV. No interaction
      effect of smoking status at Wave I and childhood ADHD symptoms was found.
      However, an indirect effect from childhood ADHD symptoms on illicit drug use was
      identified, through smoking status at Wave I. Similar results were observed for
      predicting illicit drug dependence. Conclusions: The findings support the notion
      that smoking status during early adolescence may mediate the association between
      childhood ADHD symptoms and risk of later adult drug use. Interventions to
      prevent smoking among adolescents may be particularly effective at decreasing
      subsequent drug use, especially among children with ADHD symptoms.

PMID- 29049707
TI  - Influence of staged repair and primary repair on outcomes in patients with
      complete atrioventricular septal defect and tetralogy of Fallot: a systematic
      review and meta-analysis.
AB  - OBJECTIVES: Complete atrioventricular septal defect with tetralogy of Fallot is a
      rare congenital heart disease. The combination of these lesions occurs in about
      1% of all patients with atrioventricular canal defects and in 5-6% of patients
      with tetralogy of Fallot. To assess the influence of surgical strategy on the
      survival and reintervention rate for the left atrioventricular valve and right
      ventricular outflow tract. METHODS: We analyzed all related studies since 1986.
      Thirty-eight articles were initially retrieved via PubMed/MEDLINE, Cochrane
      Central Register of Controlled Trials and Google Scholar, from which 18
      retrospective studies were included in the systematic review and 8 studies in the
      meta-analysis. RESULTS: There was no significant difference in the 6-year
      survival between staged repair and primary repair [80 patients in the primary
      group and 81 patients in the staged group; I2 = 0%; time-to-event data Peto odds
      ratio 0.66, 95% confidence interval (CI) 0.3-1.5, P = 0.31; hazard ratio 0.66,
      95% CI 0.3-1.3, P = 0.23]. Both groups had an equal reintervention rate for the
      left atrioventricular valve [75 patients in the primary group and 71 patients in
      the staged group; I2 = 0.26%; the Mantel-Haenszel odds ratio 0.60, 95% CI 0.22
      1.68, P = 0.33], but patients who received an initial palliation had a higher
      rate of reoperation on the right ventricular outflow tract [I2 = 0%; the Mantel
      Haenszel odds ratio 0.27, 95% CI 0.27-0.9988, P = 0.05]. CONCLUSIONS: Results of
      this meta-analysis reveal no difference in 6-year survival and reoperation rate
      for the left atrioventricular valve; however, patients who underwent staged
      repair had a higher rate of reintervention for the right ventricular outflow
      tract, which could be related to initially poor pulmonary bed anatomy. Therefore,
      both the primary repair and the staged repair are acceptable options for repair
      of complete atrioventricular septal defect with tetralogy of Fallot. The choice
      of surgical strategy must consider the anatomy of the pulmonary bed, patient
      condition and associated anomalies, which could affect surgical risk.

PMID- 29049709
TI  - Cybersecurity Concerns and Medical Devices: Lessons From a Pacemaker Advisory.

PMID- 29049708
TI  - Two-staged hybrid ablation of non-paroxysmal atrial fibrillation: clinical
      outcomes and functional improvements after 1 year.
AB  - OBJECTIVES: Hybrid ablation of atrial fibrillation (AF) is a promising treatment
      strategy; however, data regarding its efficacy and safety are still limited.
      METHODS: Patients with non-paroxysmal AF were enrolled. First, a thoracoscopic,
      epicardial isolation of pulmonary veins and the left atrial posterior wall ('box
      lesion') was performed; a novel unipolar/bipolar radiofrequency device was used.
      Moreover, in 12 patients enrolled thereafter, the left atrial appendage was
      occluded. Electrophysiological evaluation and catheter ablation were performed 2
      3 months later, with the goal of verifying or completing (if needed) the box
      lesion and ablation of the ganglionated plexi and the cavotricuspid isthmus.
      Outcomes were assessed using 1-week and 24-h Holter monitoring, repeated
      echocardiography and laboratory measurements. RESULTS: Thirty-eight patients (13
      persistent and 25 long-standing persistent AF) were enrolled with a mean AF
      duration of 33 +/- 32.9 months. The procedure was successfully completed in 35
      patients; 3 patients underwent only the surgical part because of a postoperative
      left atrial appendage thrombus (2 patients) and perioperative stroke (1 patient).
      After 6 months, 30 (86%) patients were arrhythmia-free, whereas 80% were also off
      antiarrhythmics. After 1 year, 28 (82%) patients were arrhythmia-free, 79% were
      off anti-arrhythmics and 47% were off anticoagulation treatment. Four (10.5%)
      serious postoperative complications occurred, including 1 stroke, 1 right phrenic
      nerve palsy and 2 pneumothoraxes with a need for drainage. Significant
      improvements were observed in echocardiographic, functional and serological
      parameters. CONCLUSIONS: Hybrid ablation is an effective treatment strategy for
      patients with persistent or long-standing persistent AF. Over 80% of patients
      were arrhythmia-free 1 year after the procedure. Sinus rhythm restoration was
      accompanied by improvements in functional, echocardiographic and serological
      markers.

PMID- 29049710
TI  - The effect of antegrade pulmonary blood flow following a late bidirectional Glenn
      procedure.
AB  - OBJECTIVES: The effect of antegrade pulmonary blood flow (APBF) has never been
      studied in the bidirectional Glenn (BDG) procedure performed late. METHODS:
      Records of 112 consecutive patients who had a BDG procedure during a 10-year
      period were reviewed retrospectively. The patients were divided into 2 groups
      based on whether APBF occurred following the BDG procedure (APBF group, n = 81)
      or not (non-APBF group, n = 31). The median age at the BDG procedure was 6.16 +/-
      3.93 years in the APBF group and 6.12 +/- 4.40 years in the non-APBF group.
      RESULTS: Demographics and pre- and intraoperative variables were comparable for
      both groups. Follow-up data were obtained for patients at the BDG stage and for
      those who had undergone the Fontan completion. Both oxygen saturation levels
      (81.72 +/- 1.976% vs 78.32 +/- 2.344%, P < 0.01) and pulmonary pressure (13.59 +/
      1.376 mmHg vs 12.90 +/- 0.978 mmHg, P = 0.012) were higher in the APBF group
      immediately after the BDG procedure. Both the duration of chest tube drainage and
      the total length of stay were longer in the APBF group. The pre-Glenn
      measurements showed a mean McGoon ratio of 1.68 +/- 0.114 in the APBF group and
      1.67 +/- 0.098 in the non-APBF group (P = 0.474). The McGoon ratios measured
      before the Fontan procedure were also comparable (1.669 +/- 0.726 vs 1.685 +/-
      0.669, P = 0.576). At the pre-Fontan measurement, there was no significant
      difference in mean pulmonary artery pressures between the groups (13.72 +/- 1.368
      vs 13.50 +/- 1.265, P = 0.653). Fifty-nine patients underwent the Fontan
      completion (43 from the APBF group and 16 from the non-APBF group) procedure with
      a median of 1.2 (APBF group) and 1.4 (non-APBF group) years after the BDG
      procedure. No significant differences between groups were observed in arterial
      oxygen saturation levels, incidence of systemic atrioventricular valve
      regurgitation or ventricular dysfunction in survivors at the last follow-up
      visit. CONCLUSIONS: The BDG procedure can be safely performed at a relatively
      older age (~6 years). APBF increases oxygen saturation but also prolongs pleural
      effusion and hospital stay. Medium-term outcomes and the Fontan completion rate
      in the APBF and the non-APBF groups are comparable. Further large studies and
      long-term follow-up are needed to clarify the effect of APBF in patients who have
      the late BDG.

PMID- 29049711
TI  - Hybrid treatment combining robotic coronary artery bypass grafting and
      percutaneous catheter radiofrequency ablation.
AB  - Isolated coronary artery bypass grafting associated with atrial fibrillation is
      routinely performed through a sternotomy, and cardiac arrest. Advancements in
      this surgical approach have led to better cosmesis, a quick postoperative
      recovery, with the same postoperative results. We report a case of a novel, less
      invasive hybrid treatment combining robot-assisted coronary artery bypass
      grafting and percutaneous radiofrequency catheter ablation.

PMID- 29049712
TI  - Easy technique for emergency fenestration in non-fenestrated Fontan patients.
AB  - The Fontan procedure is a commonly used final pathway of palliation for single
      ventricle physiology. Performing it without fenestration can avoid fenestration
      related drawbacks, including subnormal oxygen saturation, decreased exercise
      tolerance, paradoxical embolization and subsequent need for closure by catheter
      intervention. If emergency fenestration is required, however, it is not always
      technically easy to perform, particularly when the atrium is posteriorly located
      and difficult to expose. We describe an easy technique for creating an
      anastomosis using a ring-supported polytetrafluoroethylene graft to the atrium
      for fenestration, performed in 2 patients who underwent extracardiac conduit
      Fontan procedures without fenestration.

PMID- 29049713
TI  - Clampless myocardial revascularization on a healed iatrogenic aortic dissection.
AB  - Iatrogenic aortic dissection is an infrequent complication of cardiac
      catheterization (0.03-0.06%) associated with up to 19% of mortality at 30 days.
      It was reported to mostly occur when using a 6-Fr guiding catheter to cannulate
      the right coronary artery. This life-threatening complication usually requires
      early surgical management and close imaging monitoring and control of systolic
      blood pressure. This case report describes a patient with iatrogenic aortic
      dissection during cardiac catheterization in symptomatic coronary artery disease.
      Conservative management of the limited non-progressive aortic dissection was
      chosen followed by surgical revascularization with a clampless technique, despite
      the recent aortic injury.

PMID- 29049714
TI  - Unlocking the secrets to regenerating cardiac tissue: an update.
AB  - The use of extracellular matrix has evolved into a promising therapeutic approach
      for the treatment of valve disease and heart failure. Both biomechanical and
      biochemical signals for tissue remodelling require the presence of the
      extracellular matrix to recognize the remodelling signals and transfer them to
      the host stem cells. The extracellular matrix is the key to delivering these
      signals to the immigrated stem cells, and it also serves as a 'stem cell
      scaffold' making the possibility of regenerating new cardiac tissue a reality.

PMID- 29049715
TI  - Evidence of Carotenoid in Surgically Removed Lamellar Hole-Associated Epiretinal
      Proliferation.
AB  - Purpose: To determine the constituents and origin of the yellow pigment in
      surgically removed lamellar hole-associated epiretinal proliferation (LHEP) in
      patients with lamellar macular hole (LMH). Methods: This prospective case series
      comprised nine eyes with LMH in patients aged 41 to 83 years. The presence of
      LHEP was confirmed by preoperative optical coherence tomography; the distribution
      of macular pigment was observed by two-wavelength fundus autofluorescence
      technique before and after surgery. The subjects underwent a 25-gauge vitrectomy,
      and the surgically removed epiretinal membranous tissue was fixed with formalin.
      The specimens were examined using resonance Raman microscopy, and paraffin
      sections were stained with antiglial fibrillary acidic protein. Results: Seven
      cases presented with LHEP, and the presence of yellow pigment was confirmed using
      an operating microscope. Carotenoid-specific Raman signals with three major Raman
      peaks could be identified in the specimens with LHEP. These specimens were
      positive for glial fibrillary acidic protein staining. Using the fundus
      autofluorescence technique, a central defect in the distribution of the macular
      pigment was noted in the exact area of the lamellar hole. This type of defect was
      no longer visible after surgical repair of the lamellar hole. Conclusions: The
      constituents of the yellow pigment in the removed LHEP were carotenoids that
      typically originate from the macular xanthophyll pigments at the fovea. Since
      LHEP is reported to be composed of Muller cells, we hypothesize that xanthophyll
      carotenoids at the fovea are contained in the Muller cells.

PMID- 29049717
TI  - Mesopic and Photopic Rod and Cone Photoreceptor-Driven Visual Processes in Mice
      With Long-Wavelength-Shifted Cone Pigments.
AB  - Purpose: The clearer divergence in spectral sensitivity between native rod and
      human L-cone (L*-cone) opsins in the transgenic Opn1lwLIAIS mouse (LIAIS) allows
      normal visual processes mediated by these photoreceptor subtypes to be isolated
      effectively using the silent substitution technique. The objective of this study
      was to further characterize the influence of mean luminance and temporal
      frequency on the functional properties of signals originating in each
      photoreceptor separately and independently of adaptation state in LIAIS mice.
      Methods: Electroretinographic (ERG) recordings to sine-wave rod and L*-cone
      modulation at different mean luminances (0.1-130.0 cd/m2) and temporal
      frequencies (6-26 Hz) were examined in anesthetized LIAIS (N = 17) and C57Bl/6
      mice (N = 8). Results: We report maximum rod-driven response with 8-Hz modulation
      at 0.1 to 0.5 cd/m2, which was almost four times larger than maximum cone-driven
      response at 8 Hz, 21.5 to 130 cd/m2. Over these optimal luminances, both rod- and
      cone-driven response amplitudes exhibited low-pass functions with similar
      frequency resolution limits, albeit their distinct luminance sensitivities. There
      were, however, two distinguishing features: (1) the frequency-dependent amplitude
      decrease of rod-driven responses was more profound, and (2) linear relationships
      describing rod-driven response phases as a function of stimulus frequency were
      steeper. Conclusions: Employing the silent substitution method with stimuli of
      appropriate luminance on the LIAIS mouse (as on human observers) increases the
      specificity, robustness, and scope to which photoreceptor-driven responses can be
      reliably assayed compared to the standard photoreceptor isolation methods.

PMID- 29049716
TI  - Bone Marrow-Derived Cell Recruitment to the Neurosensory Retina and Retinal
      Pigment Epithelial Cell Layer Following Subthreshold Retinal Phototherapy.
AB  - Purpose: We investigated whether subthreshold retinal phototherapy (SRPT) was
      associated with recruitment of bone marrow (BM)-derived cells to the neurosensory
      retina (NSR) and RPE layer. Methods: GFP chimeric mice and wild-type (WT) mice
      were subjected to SRPT using a slit-lamp infrared laser. Duty cycles of 5%, 10%,
      15%, and 20% (0.1 seconds, 250 mW, spot size 50 MUm) with 30 applications were
      placed 50 to 100 MUm from the optic disc. In adoptive transfer studies, GFP+
      cells were given intravenously immediately after WT mice received SRPT.
      Immunohistochemistry was done for ionized calcium-binding adapter molecule-1 (IBA
      1+), CD45, Griffonia simplicifolia lectin isolectin B4, GFP or cytokeratin).
      Expression of Ccl2, Il1b, Il6, Hspa1a, Hsp90aa1, Cryab, Hif1a, Cxcl12, and Cxcr4
      mRNA and flow cytometry of the NSR and RPE-choroid were performed. Results:
      Within 12 to 24 hours of SRPT, monocytes were detected in the NSR and RPE
      choroid. Detection of reparative progenitors in the RPE occurred at 2 weeks using
      flow cytometry. Recruitment of GFP+ cells to the RPE layer occurred in a duty
      cycle-dependent manner in chimeric mice and in mice undergoing adoptive transfer.
      Hspa1a, Hsp90aa1, and Cryab mRNAs increased in the NSR at 2 hours post laser;
      Hif1a, Cxcl12, Hspa1a increased at 4 hours in the RPE-choroid; and Ccl2, Il1b,
      Ifng, and Il6 increased at 12 to 24 hours in the RPE-choroid. Conclusions: SRPT
      induces monocyte recruitment to the RPE followed by hematopoietic progenitor cell
      homing at 2 weeks. Recruitment occurs in a duty cycle-dependent manner and
      potentially could contribute to the therapeutic efficacy of SRPT.

PMID- 29049718
TI  - Wide-Field OCT Angiography Investigation of the Relationship Between Radial
      Peripapillary Capillary Plexus Density and Nerve Fiber Layer Thickness.
AB  - Purpose: To characterize the density and distribution of the radial peripapillary
      capillary plexus (RPCP) and its relationship with retinal nerve fiber layer (NFL)
      thickness in healthy subjects. Methods: Using spectral-domain optical coherence
      tomography (OCT), split-spectrum amplitude decorrelation angiography algorithm
      and automated montaging, wide-field OCT angiography (OCTA) was used to measure
      the RPCP capillary density (CD) and NFL thickness. Polar sector-average CD and
      thickness maps were also created on each eye. Results: Wide-field OCTA (8 * 8 mm)
      in 10 healthy eyes from 10 subjects demonstrated the distribution of the RPCP
      throughout the posterior pole. RPCP-CD decreases with distance from the disc, but
      along the arcuate nerve fiber bundles relatively dense (> half maximum density)
      RPCP extends more than 5 mm from the disc and includes regions superior to and
      inferior to the macula. The RPCP-CD and NFL thickness are highly correlated (R2 =
      0.85, P < 0.001) and fit well with a nonlinear stacked-layer model. The model fit
      suggests that the RPCP is present when the NFL is thicker than 17.9 MUm and
      reaches a ceiling area density of 84% and that the RPCP has an apparent volume
      density of 19% at the current instrument transverse resolution. This indicates
      that capillary overlap can be expected to occur when NFL thickness reaches 40
      MUm. Conclusions: The wide distribution of dense overlapping RPCP suggests that
      wider (up to 8 mm vertical and 7 mm horizontal) OCTA scans may be better
      investigate capillary loss in the early stages of glaucoma or other optic
      neuropathies.

PMID- 29049719
TI  - Intraday Repeatability of Bruch's Membrane Opening-Based Neuroretinal Rim
      Measurements.
AB  - Purpose: To assess possible intraday variability in Bruch's membrane opening
      based (BMO) assessment of neuroretinal rim by spectral-domain optical coherence
      tomography (SD-OCT) of the optic nerve head (ONH) as well as to evaluate its
      independence from intraindividual IOP changes. Methods: In this
      noninterventional, prospective cohort study, 51 consecutively enrolled patients
      with glaucoma or ocular hypertension underwent standardized SD-OCT of the ONH and
      IOP assessment at two different time points with a time gap of 5 hours on the
      same day. Random effects models, intraclass correlation coefficients (ICC) and
      Bland-Altman plots were used to analyze repeatability of BMO minimum rim width
      (BMO-MRW) and area (BMO-MRA) and peripapillary retinal nerve fiber layer (RNFL)
      thickness measurements. Results: Mean BMO area was 1.86 +/- 0.30 mm2. At
      baseline, mean BMO-MRW was 206.46 +/- 0.86 MUm, mean BMO-MRA was 0.89 +/- 0.34
      mm2, and mean RNFL thickness was 71.61 +/- 0.20 MUm. Within intraindividual
      measurements, mean difference was 2.95 MUm or 1.76% for BMO-MRW, 0.02 mm2 or
      2.68% for BMO-MRA, and 1.18 MUm or 1.89% for RNFL thickness. Comparing time
      points, eta2 was 0.001 (P = 0.757) for RNFL thickness, 0.043 (P = 0.01) for BMO
      MRA, and 0.07 (P = 0.06) for BMO-MRW. Intraclass correlation coefficients were
      greater than 0.994, respectively. Variability of morphometric parameters did not
      correlate to intraindividual IOP fluctuations. Conclusions: Assessment of BMO-MRW
      by SD-OCT shows high intraday repeatability, which is comparable to the parameter
      RNFL thickness. Variability seems not to be driven by typical moderate intraday
      fluctuations of IOP. The two-dimensional parameter BMO-MRA incorporates a fairly
      higher intraindividual variability.

PMID- 29049720
TI  - Optical Coherence Tomography Angiography in the Evaluation of Geographic Atrophy
      Area Extension.
AB  - Purpose: To investigate the application of optical coherence tomography
      angiography (OCT-A) in evaluation of geographic atrophy (GA) secondary to age
      related macular degeneration (AMD). Methods: Patients with GA were prospectively
      enrolled and studied with blue fundus autofluorescence (FAF), en face structural
      OCT, and OCT-A. OCT-A images were acquired using a slab of whole choroid, whereas
      en face structural OCT images were obtained at the ellipsoid zone (EZ), at the
      choroidal (CH) level, and at the scleral (SC) level. Three readers independently
      measured the GA extension areas and evaluated the foveal sparing in each
      examination. Intraobserver/interobserver agreements and agreement between each
      couple of imaging techniques were assessed. Results: A total of 47 eyes (26
      patients, mean age 76 +/- 7 years) with GA (mean area using FAF: 8.77 +/- 5.00
      mm2) were included. Intraobserver and interobserver agreement was excellent for
      all imaging techniques (intraclass correlation coefficient [ICC] > 0.985), even
      if en face EZ structural OCT revealed the poorest quality agreement limits.
      Considering the analysis between each couple of imaging techniques, ICC was
      excellent between OCT-A compared with FAF (ICC: 0.995), followed by en face
      structural OCT at CH level (ICC: 0.992), at SC level (ICC: 0.986), and at EZ
      level (ICC: 0.973). No differences were detected between multifocal and monofocal
      GA lesions. Considering the evaluation of foveal involvement, lower agreements
      were disclosed between FAF and all other imaging techniques. Conclusions: OCT-A
      is a reliable technique for easily visualizing and quantifying GA with the
      advantages, compared to current imaging techniques, of offering together both
      structural and blood flow information regarding retinal and choroidal layers and
      excluding choroidal neovascularization.

PMID- 29049721
TI  - Retinal Changes in Different Grades of Retinal Artery Occlusion: An Optical
      Coherence Tomography Study.
AB  - Purpose: To investigate layer-by-layer changes in retinal thickness and
      reflectivity regarding the severity grade of acute retinal artery occlusion (RAO)
      using spectral-domain optical coherence tomography (SD-OCT). Methods: This study
      is a retrospective, observational case-control series that took place in an
      institutional setting and included 148 eyes from 74 patients diagnosed with acute
      RAO (central or branch). SD-OCT examinations were taken at baseline. Based on OCT
      findings, RAO was categorized into three grades (incomplete, subtotal, total).
      The thickness and reflectivity of selected retinal layers were measured from SD
      OCT images. The data were compared across the three grades and against the
      contralateral eyes (controls). The main outcome measures were thickness and
      reflectivity of selected retinal layers. Results: The thickness of the inner and
      middle retinal layers differed significantly across the three RAO groups (P <
      0.001), whereas the outer retinal layer thickness remained not significantly
      different. Reflectivity values showed statistically significant differences in
      the inner, middle, and outer retinal layers, but not in the vitreous body (P <
      0.001). Conclusions: The reflectivity changes of selected retinal layers differ
      significantly regarding different grades of RAO. SD-OCT reflectivity measurement
      may be used as a noninvasive method to estimate the grade of retinal ischemia in
      RAO.

PMID- 29049722
TI  - A PPAR-Gamma Agonist Rosiglitazone Suppresses Fibrotic Response in Human
      Pterygium Fibroblasts by Modulating the p38 MAPK Pathway.
AB  - Purpose: Fibroblast activation may play an important role in pterygium
      progression. Synthetic peroxisome proliferator-activated receptor gamma (PPAR
      gamma) ligands have been shown to be effective antifibrotic agents against
      transforming growth factor beta1 (TGF-beta1) induced fibrosis in several tissues.
      We aimed to investigate the antifibrotic effects of the PPAR-gamma ligand
      rosiglitazone in pterygium fibroblasts and the underlying mechanisms. Methods:
      Profibrotic activation was induced by TGF-beta1 in primary cultured human
      pterygium fibroblasts and the effect of rosiglitazone treatment on alpha-smooth
      muscle actin (alpha-SMA), and extra cellular matrix proteins synthesis was
      detected by western blotting, real-time PCR, immunostaining, and flow cytometry.
      Pharmaceutical inhibition of PPAR-gamma receptor was used to determine the
      dependency or otherwise of rosiglitazone's action on PPAR-gamma signaling. Major
      signaling pathways downstream of TGF-beta1 were investigated by western blotting
      to assess their possible association with rosiglitazone's effect. Cell viability
      and apoptosis were investigated to assess drug-induced cytotoxicity, and the
      effect of rosiglitazone treatment on cell migration was further determined.
      Results: alpha-SMA and fibronectin synthesis induced by TGF-beta1 were suppressed
      by rosiglitazone treatment in a dose-dependent manner. Rosiglitazone also
      inhibited intrinsic TGF-beta1 expression. Smad2/3, ERK1/2, and P38 pathways were
      activated in response to TGF-beta1. Rosiglitazone suppressed TGF-beta1-induced
      P38 MAPK activation, while ERK1/2 and Smad2/3 signaling remained unaffected. The
      observed antifibrotic effect of rosiglitazone was not affected by the PPAR-gamma
      antagonist GW9662, indicating it is not PPAR-gamma dependent. Rosiglitazone also
      inhibited the proliferation and migration of pterygium fibroblasts. Conclusions:
      Rosiglitazone suppresses TGF-beta1-induced myofibroblast activation and extra
      cellular matrix synthesis in pterygium fibroblasts at least partly through the
      modulation of the p38 MAPK pathway.

PMID- 29049723
TI  - A Comparison of En Face Optical Coherence Tomography and Fundus Autofluorescence
      in Stargardt Disease.
AB  - Purpose: To compare morphologic changes on en face images derived from wide-field
      swept-source optical coherence tomography (ssOCT) to hypo- and
      hyperautofluorescent (hypoAF, hyperAF) areas on short-wavelength autofluorescence
      (SW-AF), and near-infrared (NIR)-AF in recessive Stargardt disease (STGD1).
      Methods: Wide-field ssOCT cube scans were obtained from 16 patients (16 eyes).
      Averaged B-scans and SW-AF images were obtained using Spectralis HRA+OCT. NIR-AF
      images were obtained from 6 eyes. The inner/outer segment (IS/OS), OS/RPE, and
      RPE/Bruch's membrane boundaries were segmented, and en face slab images
      generated. A subRPE slab image was used to measure the abnormal RPE area, and an
      IS/OS slab image, the IS/OS junction loss area. These were compared to hypo- and
      abnormal SW-AF areas, and hypoNIR-AF areas. A preRPE(OS) slab image was used to
      evaluate the spatial and intraretinal locations of flecks. Results: For all eyes,
      RPE atrophy was visualized as a central hyperreflective area on the subRPE slab,
      and IS/OS junction loss as an abnormal reflective area on the IS/OS slab; the
      latter was significantly larger (P = 0.04). There was good agreement between the
      hyperreflective area on the subRPE slab image and hypoSW-AF area, and between the
      abnormal reflective area on the IS/OS slab and hypo-hyperSW-AF area; the hypoNIR
      AF area indicated that the hyperreflective area on the subRPE slab underestimated
      RPE atrophy. The spatial locations of hyperreflective flecks on the en face
      preRPE(OS) slab image corresponded to those on the SW-AF images. Conclusions:
      Wide-field en face OCT imaging has the potential to be a clinically useful tool
      for the management of STGD1.

PMID- 29049724
TI  - Patients With Normal Tension Glaucoma Have Relative Sparing of the Relative
      Afferent Pupillary Defect Compared to Those With Open Angle Glaucoma and Elevated
      Intraocular Pressure.
AB  - Purpose: We determined whether there is relative sparing of pupil function in
      glaucoma patients with normal pressures compared to those with high pressures.
      Methods: A cross-sectional study was done of 68 patients with primary open angle
      glaucoma (POAG): 38 had normal IOPs on all-day phasing before treatment (never
      >21 mm Hg), with confirmed progression of glaucomatous optic neuropathy (NTG) and
      30 had glaucomatous optic neuropathy associated with elevated intraocular
      pressures (>25 mm Hg; HP-POAG). The relative afferent pupillary defect (RAPD) was
      quantified with the RAPDx device, and mean deviation of visual field loss was
      obtained from reliable Humphrey visual fields. Outcomes measures evaluated were
      difference in slope between NTG and HP-POAG when plotting: (1) RAPD score against
      difference in mean deviation (MD) between eyes, and (2) RAPD score against
      difference in RNFL thickness between eyes. Results: The slopes for magnitude of
      RAPD versus difference in MD were -0.06 (95% confidence interval [CI], -0.076, 
      0.044) for patients with NTG and -0.08 (95% CI, -0.109, -0.067) for those with HP
      POAG. Fitting the interaction term showed a statistically significant difference
      between the slopes (0.023; 95% CI [0.0017, 0.0541]; P value = 0.037; HP-POAG
      reference group). Thus, for difference in MD, the slope for patients with NTG was
      flatter than the slope for those with HP-POAG. Conclusions: Glaucoma patients
      with NTG have a lesser RAPD for a given level of intereye difference of HVF MD,
      compared to patients with high IOPs. This suggests that damage to intrinsically
      photosensitive retinal ganglion cells (ipRGCs) differs between the normal and
      high-pressure forms of open-angle glaucoma (OAG), and supports the theory that
      mitochondrial optic neuropathies may have a role in the group of diagnoses
      currently termed normal tension glaucoma.

PMID- 29049725
TI  - CD11b and CD200 on Circulating Monocytes Differentiate Two Angiographic Subtypes
      of Polypoidal Choroidal Vasculopathy.
AB  - Purpose: To investigate surface expression of CD11b and CD200 on circulating
      monocytes in patients with polypoidal choroidal vasculopathy (PCV). Methods: This
      was a prospective case-control study of patients with PCV (n = 27), age-matched
      healthy controls (n = 27), and patients with neovascular AMD (n = 49). All
      participants underwent a comprehensive ocular examination. Fluorescein and
      indocyanine green angiography were performed in patients suspected of neovascular
      AMD or PCV. Polypoidal choroidal vasculopathy was angiographically categorized
      into those with a strong presence of a branching vascular network (BVN) (type 1)
      or with a faint/no clear presence of a BVN (type 2). Fresh venous blood was
      stained with fluorescent antibodies for flow cytometric analyses. We compared the
      percentages of CD11b+, CD200+, and CD11b+CD200+ monocytes between groups of
      diagnosis and between different angiographic subtypes of PCV. Results: Overall,
      CD11b+ monocytes were both increased in patients with PCV and neovascular AMD.
      CD200+ and CD11b+CD200+ monocytes were increased in patients with neovascular
      AMD. An age-related increase in CD11b+CD200+ monocytes was absent in patients
      with PCV and neovascular AMD. Patients with PCV type 1 had significantly higher
      CD11b+, CD200+, and CD11b+CD200+ monocytes, whereas patients with PCV type 2 had
      levels similar to that in healthy controls. Conclusions: We found that PCV is
      immunologically heterogeneous with significant differences between angiographic
      subtypes. Increased CD11b+ and CD200+ monocytes in those with a strong presence
      of BVN indicate that BVN development may be associated with retinal injury and a
      VEGF-mediated process that is either reflected or propelled by systemic changes
      in monocytes.

PMID- 29049727
TI  - The Diameter of Retinal Vessels Is Affected by Transient Ischemia of the Arm in
      Normal Persons.
AB  - Purpose: Remote ischemic conditioning (RIC) implies that transient ischemia in a
      limb can affect perfusion in a target organ elsewhere in the body. The changes in
      perfusion can be assumed to be paralleled by changes in the vessel diameters in
      the target organ. It remains to be elucidated whether the diameter of normal
      retinal vessels can be used as a marker of RIC in vivo. Methods: In 20 normal
      persons aged 20 to 31 years the Dynamic Vessel Analyzer (DVA) was used to measure
      the resting diameter and diameter changes during isometric exercise and flicker
      stimulation before, immediately after, and 1 hour after RIC induced by transient
      ischemia in the left arm. Results: The baseline diameter of retinal venules was
      reduced nonsignificantly immediately after (P = 0.07) and significantly 1 hour
      after RIC (P = 0.009), whereas the baseline diameter of arterioles was unaffected
      by the intervention (P = 0.61). Arterial constriction induced by isometric
      exercise was significantly reduced immediately after RIC (P = 0.04), but not 1
      hour after RIC (P = 0.99). None of the other diameter responses were affected by
      RIC (P = 0.22 for all comparisons). Conclusions: The diameter of retinal vessels
      might potentially be a marker of ischemic conditioning in the body in general.
      The effect of RIC on retinal vascular diseases where ischemia is a part of the
      pathogenesis should be investigated.

PMID- 29049726
TI  - Comparison of Sectoral Structure-Function Relationships in Glaucoma: Vessel
      Density Versus Thickness in the Peripapillary Retinal Nerve Fiber Layer.
AB  - Purpose: To compare the sectoral structure-function relationships in glaucoma
      between two structural parameters, vessel density (VD) and thickness, in the
      peripapillary retinal nerve fiber layer (RNFL). Methods: Optical coherence
      tomography (OCT) angiography (AngioVue/RTVue-XR) for VD and OCT (RS-3000) for
      peripapillary RNFL thickness were performed in 129 eyes from 129 subjects (94
      glaucoma, 17 glaucoma suspects, and 18 normal eyes). Humphrey visual field (VF)
      tests were performed using a SITA standard 24-2 program. Sectoral structure
      function relationships based on the Garway-Heath map were compared between VD and
      thickness using a semipartial correlation coefficient (sr) and partial residual
      plots determined by multiple linear regression models controlling for the effects
      of sex, age, axial length, disc area, beta- and gamma- parapapillary atrophy
      (PPA) zones, and signal strength index (SSI). Results: For all VF sectors, the
      sr2 of VD was largest when the VD sector corresponded to the VF sector (sr2: 0.17
      0.39). In contrast, in only three sectors was the sr2 of thickness largest when
      the thickness sector corresponded to the VF sector (sr2: 0.02-0.34): the inferior
      temporal, temporal, and superior temporal sectors. The partial residual plots
      against VD showed more linear relationships with VF sensitivity than those
      against thickness in the qualitative evaluation of fitting by locally weighted
      scatterplot smoothing. Eyes with larger SSI had higher VD, whereas eyes with a
      larger extension of the PPA zone into the VD measurement area had lower VD.
      Conclusions: Peripapillary RNFL VD and thickness have different characteristic
      sectoral structure-function relationships in glaucoma.

PMID- 29049728
TI  - Surgically Induced Focal Retinal Detachment Does Not Cause Detectable SD-OCT
      Retinal Changes in Normal Human Retina.
AB  - Purpose: Induction of focal retinal detachment (RD) for subretinal delivery of
      stem cells and gene therapy is increasingly common. In order to determine if this
      procedure has an adverse impact on the retina, we use spectral-domain optical
      coherence tomography (SD-OCT) to evaluate the pre- and postoperative retinal
      anatomy of the incidentally detached normal retina surrounding large submacular
      hemorrhages (SMH) during surgical displacement procedures. Methods:
      Retrospective, observational study of human subjects with monocular SMH evaluated
      before and after surgical displacement using clinical exam, fundus photography,
      and SD-OCT. Manual measurements of the inner retinal thickness (IRT), outer
      retinal thickness (ORT), and full retinal thickness (FRT) were made in regions
      involving the SMH and surrounding normal retina. Comparison of retinal thickness
      measurements was made using the Wilcoxon signed-rank test. Results: Seven eyes
      were included in this study. All eyes successfully underwent surgical
      displacement of SMH. Visual acuity improved in 6/7 subjects and was unchanged in
      the remaining subject. Incidental RD of the normal retinal regions surrounding
      the SMH did not cause any significant change in IRT, ORT, or FRT that was
      detectable by SD-OCT. In contrast, mean FRT overlying regions with SMH was
      significantly greater before surgery compared to after displacement of SMH or
      normal adjacent retina. Conclusions: Surgically induced focal RD does not cause
      detectable retinal changes in the incidentally detached normal retina surrounding
      large SMH. Therefore, surgical induction of focal RD should not be considered to
      have the same adverse impact on the retina as pathologic RD.

PMID- 29049730
TI  - Another Piece of the Puzzle: MYOC and Myocilin Glaucoma.

PMID- 29049729
TI  - Myocilin Regulates Metalloprotease 2 Activity Through Interaction With TIMP3.
AB  - Purpose: To elucidate functions of wild-type myocilin, a secreted glycoprotein
      associated with glaucoma. Methods: Lysates of mouse eyes were used for
      immunoprecipitation with affinity-purified antibodies against mouse myocilin.
      Shotgun proteomic analysis was used for the identification of proteins
      interacting with myocilin. Colocalization of myocilin and tissue inhibitor of
      metalloproteinases 3 (TIMP3) in different eye structures was investigated by a
      multiplex fluorescent in situ hybridization and immunofluorescent labeling with
      subsequent confocal microscopy. Matrix metalloproteinase 2 (MMP2) activity assay
      was used to test effects of myocilin on TIMP3 inhibitory action. Results: TIMP3
      was identified by a shotgun proteomic analysis as a protein that was
      coimmunoprecipitated with myocilin from eye lysates of wild-type and transgenic
      mice expressing elevated levels of mouse myocilin but not from lysates of
      transgenic mice expressing mutated mouse myocilin. Interaction of myocilin and
      TIMP3 was confirmed by coimmunoprecipitation of myocilin and TIMP3 from HEK293
      cells transiently transfected with cDNAs encoding these proteins. The
      olfactomedin domain of myocilin is essential for interaction with TIMP3. In the
      eye, the main sites of myocilin and TIMP3 colocalization are the trabecular
      meshwork, sclera, and choroid. Using purified proteins, it has been shown that
      myocilin markedly enhanced the inhibitory activity of TIMP3 toward MMP2.
      Conclusions: Myocilin may serve as a modulator of TIMP3 activity via interactions
      with the myocilin olfactomedin domain. Our data imply that in the case of
      MYOCILIN null or some glaucoma-causing mutations, inhibitory activity of TIMP3
      toward MMP2 might be reduced, mimicking deleterious mutations in the TIMP3 gene.

PMID- 29049731
TI  - Factors Affecting Mydriasis-Free Flicker ERGs Recorded With Real-Time Correction
      for Retinal Illuminance: Study of 150 Young Healthy Subjects.
AB  - Purpose: A small, full-field flicker electroretinogram (ERG) recording system was
      recently developed to record flicker ERGs without mydriasis (RETeval). The device
      delivers a stimulus with constant retinal illuminance by adjusting the retinal
      luminance to compensate for changes in the pupillary area. The purpose of this
      study was to determine what factors affect the fundamental components of the
      flicker ERGs recorded by RETeval in young healthy subjects. Methods: Flicker ERGs
      were recorded with the RETeval system from 150 eyes of 150 young healthy subjects
      (age, 20-29 years). Univariate and multivariate linear regression analyses were
      performed to identify the factors that affected the implicit times and amplitudes
      of the fundamental component of the flicker ERGs. The independent variables
      included age, sex, refractive error, axial length, and pupillary area. Results:
      Multivariate regression analyses indicated that a longer axial length (P = 0.03)
      and larger pupillary area (P = 0.008) were independent factors that were
      significantly associated with longer implicit times of the fundamental component
      of the flicker ERGs. Multivariate regression analyses also showed that the female
      sex (P = 0.03) was an independent factor, which was significantly associated with
      larger amplitude fundamental component of the flicker ERGs. Conclusions: These
      results indicate that the fundamental components of the RETeval flicker ERGs are
      significantly affected by the axial length, pupillary area, and sex of young
      healthy subjects. The results also suggest that it would be better to compensate
      for the Stiles-Crawford effect when flicker ERGs are recorded with natural
      pupils.

PMID- 29049732
TI  - Iron-Chelating Drugs Enhance Cone Photoreceptor Survival in a Mouse Model of
      Retinitis Pigmentosa.
AB  - Purpose: Retinitis pigmentosa (RP) is a group of hereditary retinal degeneration
      in which mutations commonly result in the initial phase of rod cell death
      followed by gradual cone cell death. The mechanisms by which the mutations lead
      to photoreceptor cell death in RP have not been clearly elucidated. There is
      currently no effective treatment for RP. The purpose of this work was to explore
      iron chelation therapy for improving cone survival and function in the rd10 mouse
      model of RP. Methods: Two iron-chelating drugs, 5-(4-(2-hydroxyethyl) piperazin-1
      yl (methyl)-8-hydroxyquinoline (VK28) and its chimeric derivative 5-(N-methyl-N
      propargyaminomethyl)-quinoline-8-oldihydrochloride (VAR10303), were injected
      intraperitoneally to rd10 mice every other day starting from postnatal day 14. We
      investigate the effects of the two compounds on cone rescue at three time points,
      using a combination of immunocytochemistry, RT-PCR, Western blot analysis, and a
      series of visual function tests. Results: VK28 and VAR10303 treatments partially
      rescued cones, and significantly improved visual function in rd10 mice. Moreover,
      we showed that the neuroprotective effects of VK28 and VAR10303 were correlated
      to inhibition of neuroinflammation, oxidative stress, and apoptosis. Furthermore,
      we demonstrated that downregulation of NF-kB and p53 is likely to be the
      mechanisms by which proinflammatory mediators and apoptosis are reduced in the
      rd10 retina, respectively. Conclusions: VK28 and VAR10303 provided partial
      histologic and functional rescue of cones in RD10 mice. Our study demonstrated
      that iron chelation therapy might represent an effective therapeutic strategy for
      RP patients.

PMID- 29049733
TI  - Tunneling Nanotubes are Novel Cellular Structures That Communicate Signals
      Between Trabecular Meshwork Cells.
AB  - Purpose: The actin cytoskeleton of trabecular meshwork (TM) cells plays a role in
      regulating aqueous humor outflow. Many studies have investigated stress fibers,
      but F-actin also assembles into other supramolecular structures including
      filopodia. Recently, specialized filopodia called tunneling nanotubes (TNTs) have
      been described, which communicate molecular signals and organelles directly
      between cells. Here, we investigate TNT formation by TM cells. Methods: Human TM
      cells were labeled separately with the fluorescent dyes, DiO and DiD, or with
      mitochondrial dye. Fixed or live TM cells were imaged using confocal microscopy.
      Image analysis software was used to track fluorescent vesicles and count the
      number and length of filopodia. The number of fluorescently labeled vesicles
      transferred between cells was counted in response to specific inhibitors of the
      actin cytoskeleton. Human TM tissue was stained with phalloidin. Results: Live
      cell confocal imaging of cultured TM cells showed transfer of fluorescently
      labeled vesicles and mitochondria via TNTs. In TM tissue, a long (160 MUm) actin
      rich cell process bridged an intertrabecular space and did not adhere to the
      substratum. Treatment of TM cells with CK-666, an Arp2/3 inhibitor, significantly
      decreased the number and length of filopodia, decreased transfer of fluorescently
      labeled vesicles and induced thick stress fibers compared to vehicle control.
      Conversely, inhibiting stress fibers using Y27632 increased transfer of vesicles
      and induced long cell processes. Conclusions: Identification of TNTs provides a
      means by which TM cells can directly communicate with each other over long
      distances. This may be particularly important to overcome limitations of
      diffusion-based signaling in the aqueous humor fluid environment.

PMID- 29049734
TI  - A Computational Approach From Gene to Structure Analysis of the Human ABCA4
      Transporter Involved in Genetic Retinal Diseases.
AB  - Purpose: The aim of this article is to report the investigation of the structural
      features of ABCA4, a protein associated with a genetic retinal disease. A new
      database collecting knowledge of ABCA4 structure may facilitate predictions about
      the possible functional consequences of gene mutations observed in clinical
      practice. Methods: In order to correlate structural and functional effects of the
      observed mutations, the structure of mouse P-glycoprotein was used as a template
      for homology modeling. The obtained structural information and genetic data are
      the basis of our relational database (ABCA4Database). Results: Sequence
      variability among all ABCA4-deposited entries was calculated and reported as
      Shannon entropy score at the residue level. The three-dimensional model of ABCA4
      structure was used to locate the spatial distribution of the observed variable
      regions. Our predictions from structural in silico tools were able to accurately
      link the functional effects of mutations to phenotype. The development of the
      ABCA4Database gathers all the available genetic and structural information,
      yielding a global view of the molecular basis of some retinal diseases.
      Conclusions: ABCA4 modeled structure provides a molecular basis on which to
      analyze protein sequence mutations related to genetic retinal disease in order to
      predict the risk of retinal disease across all possible ABCA4 mutations.
      Additionally, our ABCA4 predicted structure is a good starting point for the
      creation of a new data analysis model, appropriate for precision medicine, in
      order to develop a deeper knowledge network of the disease and to improve the
      management of patients.

PMID- 29049735
TI  - Clinical and Biological Evaluations of Biodegradable Collagen Matrices for
      Glaucoma Drainage Device Implantation.
AB  - Purpose: To characterize the clinical and biological properties of biodegradable
      collagen matrices (BCMs) for possible glaucoma drainage device implantation.
      Methods: A total of 68 refractory glaucoma eyes, followed up postoperatively for
      at least 6 months, were consecutively enrolled after retrospective chart review.
      The BCM-augmented Ahmed valve implantations (BAAVI) using our Ologen-6 and Ologen
      7 valves were performed and compared with a conventional method. Complete
      surgical success was defined as an IOP of <=21 mm Hg (IOP 1) or <=17 mm Hg (IOP
      2) without antiglaucoma medications. Qualified success was defined as an IOP <=21
      mm Hg with or without antiglaucoma medications. The biological properties of each
      BCM were assessed by enzymatic degradation rates via collagenase under ocular
      physiological conditions. Results: The mean ages and preoperative IOPs were
      similar for the groups. In the conventional, BAAVI with Ologen-6, and BAAVI with
      Ologen-7 groups, complete success rates with target IOP 1 were 29.2%, 40.0%, and
      66.7%; those with target IOP 2 were 12.5%, 30.0%, and 45.8%; qualified success
      rates were 45.8%, 55.0%, and 75.0%, respectively. The enzymatic degradation rate
      of Ologen-7 was significantly slower than that of Ologen-6 (12.5 * 10-3 vs. 28.8
      * 10-3). Conclusions: The surgical success rate was highest in the Ologen-7 BAAVI
      group, with the lowest dependency on postoperative antiglaucoma medication use
      compared with the conventional and Ologen-6 BAAVI groups. The clinical results
      correlated with the different biological and physicochemical properties based on
      the degree of enzymatic degradation and on the structural morphology.

PMID- 29049736
TI  - Lamina Cribrosa Pore Shape and Size as Predictors of Neural Tissue Mechanical
      Insult.
AB  - Purpose: The purpose of this study was to determine how the architecture of the
      lamina cribrosa (LC) microstructure, including the shape and size of the lamina
      pores, influences the IOP-induced deformation of the neural tissues within the LC
      pores using computational modeling. Methods: We built seven specimen-specific
      finite element models of LC microstructure with distinct nonlinear anisotropic
      properties for LC beams and neural tissues based on histological sections from
      three sheep eyes. Changes in shape (aspect ratio and convexity) and size (area
      and perimeter length) due to IOP-induced hoop stress were calculated for 128 LC
      pores. Multivariate linear regression was used to determine if pore shape and
      size were correlated with the strain in the pores. We also compared the
      microstructure models to a homogenized model built following previous approaches.
      Results: The LC microstructure resulted in focal tensile, compressive, and shear
      strains in the neural tissues of the LC that were not predicted by homogenized
      models. IOP-induced hoop stress caused pores to become larger and more convex;
      however, pore aspect ratio did not change consistently. Peak tensile strains
      within the pores were well predicted by a linear regression model considering the
      initial convexity (negative correlation, P < 0.001), aspect ratio (positive
      correlation, P < 0.01), and area (negative correlation, P < 0.01). Significant
      correlations were also found when considering the deformed shape and size of the
      LC pores. Conclusions: The deformation of the LC neural tissues was largely
      dependent on the collagenous LC beams. Simple measures of LC pore shape and area
      provided good estimates of neural tissue biomechanical insult.

PMID- 29049737
TI  - Introduction of the MDM2 T309G Mutation in Primary Human Retinal Epithelial Cells
      Enhances Experimental Proliferative Vitreoretinopathy.
AB  - Purpose: The murine double minute (MDM)2 is a critical negative regulator of the
      p53 tumor suppressor, and MDM2 SNP309G is associated with a higher risk of
      proliferative vitreoretinopathy (PVR); in addition, the MDM2 T309G created using
      clustered regularly interspaced short palindromic repeats (CRISPR)/associated
      endonuclease (Cas)9 enhances normal rabbit vitreous-induced expression of MDM2
      and survival of primary human retinal pigment epithelial (hRPE) cells in vitro.
      The goal of this study was to determine whether this MDM2 T309G contributes to
      the development of experimental PVR. Methods: hRPE cells expressing MDM2 T309G or
      T309T only were treated with vitreous from human PVR donors (HV). The expression
      of MDM2 and p53 in the treated cells was examined by Western blot. The in vitro
      vitreous-induced cellular responses, such as contraction were assessed, and PVR
      was induced by intravitreal injection of the hRPE cells with MDM2 T309G or T309T
      only into rabbit eyes. Results: Western blot analyses indicated that treatment of
      hRPE cells with HV led to a significant increase (1.7 +/- 0.2-fold) in the
      expression of MDM2 and a significant decrease in p53 in the cells expressing MDM2
      T309G compared with those with MDM2 T309T. In addition, HV promoted contraction
      of the hRPE cells expressing MDM2 T309G significantly more than those with MDM2
      T309T only. Furthermore, MDM2 T309G in the hRPE cells enhanced the development of
      PVR in a rabbit model. Conclusions: The MDM2 SNP309 in RPE cells enhances their
      potential of PVR pathogenesis.

PMID- 29049738
TI  - A Genome-Wide Scan for MicroRNA-Related Genetic Variants Associated With Primary
      Open-Angle Glaucoma.
AB  - Purpose: To identify microRNAs (miRNAs) involved in primary open-angle glaucoma
      (POAG), using genetic data. MiRNAs are small noncoding RNAs that
      posttranscriptionally regulate gene expression. Genetic variants in miRNAs or
      miRNA-binding sites within gene 3'-untranslated regions (3'UTRs) are expected to
      affect miRNA function and contribute to disease risk. Methods: Data from the
      recent genome-wide association studies on intraocular pressure, vertical cup-to
      disc ratio (VCDR), cupa area and disc area were used to investigate the
      association of miRNAs with POAG endophenotypes. Putative targets of the
      associated miRNAs were studied according to their association with POAG and
      tested in cell line by transfection experiments for regulation by the miRNAs.
      Results: Of 411 miRNA variants, rs12803915:A/G in the terminal loop of pre-miR
      612 and rs2273626:A/C in the seed sequence of miR-4707 were significantly
      associated with VCDR and cup area (P values < 1.2 * 10-4). The first variant is
      demonstrated to increase the miR-612 expression. We showed that the second
      variant does not affect the miR-4707 biogenesis, but reduces the binding of miR
      4707-3p to CARD10, a gene known to be involved in glaucoma. Moreover, of 72,052
      miRNA-binding-site variants, 47 were significantly associated with four POAG
      endophenotypes (P value < 6.9 * 10-6). Of these, we highlighted 10 variants that
      are more likely to affect miRNA-mediated gene regulation in POAG. These include
      rs3217992 and rs1063192, which have been shown experimentally to affect miR-138
      3p- and miR-323b-5p-mediated regulation of CDKN2B. Conclusions: We identified a
      number of miRNAs that are associated with POAG endophenotypes. The identified
      miRNAs and their target genes are candidates for future studies on miRNA-related
      therapies for POAG.

PMID- 29049740
TI  - Phenotypic Plasticity in Uveal Melanoma Is Not Restricted to a Tumor
      Subpopulation and Is Unrelated to Cancer Stem Cell Characteristics.
AB  - Purpose: Uveal melanoma (UM) is the most common primary intraocular malignancy in
      adults and approximately half of those diagnosed will die of metastasis. This
      study investigates whether UM progression is driven by a subpopulation of stem
      like cells, termed "cancer stem cells" (CSCs). Methods: Expression of postulated
      stem cell markers aldehyde dehydrogenase (ALDH), CD44, and CD133 was analyzed in
      UM cell lines and primary UM short-term cultures (STCs) established from tumor
      samples. Additionally, the notion of a "cellular hierarchy" within UM was
      investigated. Finally, the phenomenon of phenotypic plasticity in response to
      environmental factors was explored. Results: We demonstrate that expression of
      ALDH, CD44, and CD133 does not select for a subpopulation of stem-like cells in
      either UM cell lines or UM STCs. Furthermore, there is an absence of a cellular
      hierarchy in cell lines and all cells in culture are able to drive tumor
      progression. Last, we show that established UM cell lines and UM STCs are plastic
      in nature and switch their phenotype in response to environmental stimuli.
      Conclusions: We hypothesize that this capacity to undergo phenotypic plasticity
      may be a consequence of neural crest lineage and renders the exploration of the
      CSC hypothesis extremely challenging in UM.

PMID- 29049739
TI  - Cataract Avoidance With Proton Therapy in Ocular Melanomas.
AB  - Purpose: The lens is a radiosensitive organ. Any dose of cephalic irradiation can
      give rise to radiation-induced cataracts. Contrary to other forms of
      radiotherapy, proton therapy (PT) can spare all or part of the lens due to
      accurate dose deposition. We investigated whether a lens-sparing approach was
      relevant to avoid cataracts in uveal melanoma patients. Methods: Patients were
      referred for PT from onco-ophthalmologists of private and academic institutions.
      Patients without preexisting cataracts or implants were entered in a prospective
      database. Dose thresholds responsible for cataracts were investigated in volumes
      of lens or lens periphery. Lens opacifications and de novo vision-impairing
      cataracts (VICs) had biannual follow up by ophthalmologists blinded to lens dose.
      Correlations between dose-volume relationships and VICs were assessed using
      univariate/multivariate regressions. Results: Between 1991 and 2015, 1696 uveal
      melanoma patients were consecutively treated with PT. After a median follow up of
      48 months, 14.4% and 8.7% of patients had cataracts and VIC within median times
      of 19 and 28 months, respectively. Median values of mean lens and lens periphery
      doses were 1.1 (radiobiologically effective [RBE] dose in photon-equivalent grays
      [GyRBE]) and 6.5 GyRBE, respectively. The lens received no dose in 25% of the
      patients. At an irradiated lens volume of <=5%, there was no significantly
      increased risk for VIC below a dose of 10 GyRBE. Conclusions: A lens-sparing
      approach is feasible and results not only in reduced need for cataract surgery
      but also in better fundus-based tumor control. Reassessment of radioprotection
      rules for lens dose thresholds may follow.

PMID- 29049741
TI  - Transapical transcatheter aortic valve implantation in patients with a low
      ejection fraction.
AB  - OBJECTIVES: It may be expected that patients with left ventricular dysfunction
      may be at greater risk of complications after transcatheter aortic valve
      implantation (TAVI) via transapical (TA) access compared with via transfemoral
      (TF) access. There is a lack of data comparing the outcomes of TAVI using TA and
      TF access in patients with a reduced left ventricular ejection fraction (EF).
      METHODS: This is a retrospective analysis of data from a high-volume heart centre
      in Germany. TAVI access route assignment was based on a 'best for TF' approach,
      where only patients who met a strict set of criteria underwent TF-TAVI, with the
      remainder receiving TA-TAVI. For this analysis, patients were included if they
      had a pre-TAVI EF of <= 40%. Early mortality and late (1-year) mortality were
      compared through multivariate logistic regression. RESULTS: A total of 342
      patients in the registry had an EF of <= 40%, of which 74.9% underwent TA-TAVI
      and 25.1% underwent TF-TAVI. Higher proportions of the TA group presented with
      certain comorbidities, and their logistic EuroSCORE and Society of Thoracic
      Surgeons (STS) risk scores were higher than in the TF group. At 1 year, TA access
      was associated with greater mortality in the univariate analysis (odd ratio 2.43;
      95% confidence interval 1.04-5.69). However, after multivariate adjustment, no
      significant differences were found in either 30-day or 1-year mortality rates.
      CONCLUSIONS: The data suggest that, for patients with a reduced EF, TA-TAVI is
      not associated with a poorer outcome compared with TF-TAVI. Therefore, TA access
      should not be discounted based on the presence of left ventricular dysfunction
      alone.

PMID- 29049742
TI  - Preoperative six-minute walk distance is associated with pneumonia after lung
      resection.
AB  - OBJECTIVES: Little is known about the relationship between preoperative physical
      fitness and postoperative pneumonia after lung resection. We examined the
      association between preoperative 6-min walk distance (6MWD) and postoperative
      pneumonia. METHODS: A retrospective study was conducted on patients with
      malignant lung tumours who were scheduled to undergo lung resection at Nagoya
      University Hospital from January 2014 to December 2015. Preoperative pulmonary
      function tests and the 6-min walk test were assessed. A logistic regression model
      and receiver operating characteristic curves were used to analyse clinical
      variables and compare the performance on 6MWD, forced expiratory volume in 1 s
      and diffusion capacity of the lung for carbon monoxide. RESULTS: The data from a
      total of 321 patients including 283 with primary lung cancer and 38 with
      metastatic lung tumours were analysed. Pneumonia developed in 13 patients and
      caused longer hospital stays after surgery. The preoperative 6MWD of patients
      with pneumonia was significantly lower than that without pneumonia (425 vs 500 m,
      P = 0.002). In receiver operating characteristic analysis, 6MWD <= 450 m was a
      threshold for predicting postoperative pneumonia with 69.2% sensitivity and 71.1%
      specificity. A 6MWD <= 450 m, forced expiratory volume in 1 s <80% of the
      predicted value, diffusion capacity of the lung for carbon monoxide <80% of the
      predicted value, serum albumin <3.5 g/dl and blood loss during surgery >=200 g
      were significantly associated with postoperative pneumonia in a logistic model.
      CONCLUSIONS: Preoperative 6MWD was significantly associated with postoperative
      pneumonia in patients who underwent lung resection for malignancies.

PMID- 29049743
TI  - Additional veno-venous gas exchange as a problem-solving strategy for an
      oxygenator not transferring oxygen in paediatric cardiopulmonary bypass.
AB  - OBJECTIVES: Oxygenator failure during cardiopulmonary bypass constitutes a life
      threatening event, especially when perfusion is conducted under normothermia. An
      alternative solution to emergency oxygenator changeover is described. METHODS: A
      supplementary oxygenator is added in the venous line without interrupting
      perfusion. De-airing is achieved through the cardiotomy reservoir. Oxygen supply
      is adapted to ensure physiologic partial oxygen pressure. RESULTS: On 5 occasions
      in the past 4 years, Capiox Baby FX 05 oxygenator (n = 4) and Capiox FX15 (n = 1)
      failed to exchange blood gases after bypass run ranging from 290 min to 563 min.
      Hypoxia ensued with partial oxygen pressure values of 49-79 mmHg with a fraction
      of inspired oxygen of 1. An additional veno-venous Terumo Capiox FX 05 oxygenator
      immediately improved oxygenation with resulting partial oxygen pressure
      increasing to at least 291 mmHg. CONCLUSIONS: An additional veno-venous
      oxygenator effectively corrects failing oxygenator during cardiopulmonary bypass.
      The method does not require circulation arrest. It does not carry the risk of air
      embolism. It can be carried out without any help from a second perfusionist or
      member of operation team.

PMID- 29049744
TI  - Extended pleurectomy decortication for malignant pleural mesothelioma in the
      elderly: the need for an inclusive yet selective approach.
AB  - OBJECTIVES: The median age at diagnosis of patients with pleural mesothelioma in
      the UK is 73 years. Recent series have shown the feasibility of extended
      pleurectomy decortication in the elderly, but with continuing debate about the
      efficacy of this treatment, we reviewed our experience to identify more detailed
      selection criteria. METHODS: We reviewed prospectively collected data on all
      patients from 1999 to 2016 undergoing extended pleurectomy decortication. We
      compared clinical and pathological outcomes and survival data from patients 70
      years and older (>=70 years) with those younger than 70 years (<70 years).
      RESULTS: Eighty-two of the 300 (27.3%) patients were >=70 years of age at the
      time of surgery. More patients in the elderly group required intensive care
      postoperatively (6.2 vs 16.7%, P = 0.01) and developed atrial fibrillation (14.4
      vs 24.4%, P = 0.05). There was no intergroup difference in length of hospital
      stay or in in-hospital, 30-day or 90-day mortality. Elderly patients were less
      likely to receive neoadjuvant (<70 years 21.2%, >=70 years 11.0%; P = 0.045) or
      adjuvant chemotherapy (<70 years 45.4%, >=70 years 29.3%; P = 0.04). Median
      overall survival was similar: <70 years 14.0 months, >=70 years 10.3 months; P =
      0.29. However, in node-positive patients, survival was poorer in the elderly
      (13.0 vs 9.1 months, P = 0.05), particularly in those with non-epithelioid
      tumours (3.8 vs 6.7 months, P = 0.04). On multivariable analysis, age was not a
      significant prognostic factor, although lack of adjuvant therapy (P = 0.001) and
      admission to the intensive care unit (P < 0.001) remained poor prognostic
      factors. CONCLUSIONS: Although age in isolation should not be an exclusion
      criterion for extended pleurectomy decortication for mesothelioma, in the
      elderly, a more rigorous preoperative evaluation of nodal disease and an
      additional assessment of fitness for adjuvant chemotherapy are recommended.

PMID- 29049745
TI  - Clinical presentation and surgical treatment of primary pulmonary artery sarcoma.
AB  - OBJECTIVES: Pulmonary artery sarcoma (PAS) is a rare and devastating disease. The
      diagnosis modality and optimal surgical strategy remain unclear. The aim of this
      study was to report our surgical experience in this disease. METHODS: Between
      2000 and 2017, 13 patients underwent operations for PAS at our institution. Five
      patients underwent tumour resection alone, whereas the other 8 patients received
      pulmonary endarterectomy. The medical records were retrospectively reviewed to
      evaluate the clinical characteristics, operative findings and the postoperative
      outcomes. RESULTS: There were 2 perioperative deaths, both had unresolved severe
      pulmonary hypertension. Follow-up was completed for all patients with a mean
      duration of 14.3 months (1-48 months). During follow-up, 6 patients died after a
      mean survival time of 20.2 months (4-48 months). For the 5 patients alive at
      follow-up (mean duration of 7.2 months), 3 already had local recurrence. For all
      13 patients, the cumulative survival rates at 1, 2 and 3 years were 56.4, 37.6
      and 18.8%, respectively. The 8 patients treated with pulmonary endarterectomy
      seemed to have a better survival rate compared with the remaining 5 patients
      without endarterectomy, although the difference was not statistically
      significant. CONCLUSIONS: Primary PAS is often mistaken for chronic pulmonary
      thromboembolism. Surgical intervention is the mainstay of treatment for PAS, but
      the prognosis after surgery remains poor. Compared to isolated tumour resection,
      pulmonary endarterectomy seemed to yield a better survival rate.

PMID- 29049746
TI  - Degree of pulmonary fissure completeness can predict postoperative
      cardiopulmonary complications and length of hospital stay in patients undergoing
      video-assisted thoracoscopic lobectomy for early-stage lung cancer.
AB  - OBJECTIVES: To estimate the effects of pulmonary fissure completeness on
      postoperative cardiopulmonary complications (PCCs) and hospital stay in patients
      undergoing video-assisted thoracoscopic surgery lobectomy for early-stage non
      small-cell lung cancer. METHODS: We performed a single-centre retrospective
      analysis based on the prospectively maintained data of our institution during the
      study period. Demographic differences between the PCC group and the non-PCC group
      were initially examined. Then, the patients were classified into 3 groups
      according to their fissure sum averages (FSAs: 0 <= FSA <= 1, 1 < FSA <= 2, 2 <
      FSA <= 3) calculated by fissure development scores. The differences in PCC
      incidences and hospital stay between these 3 groups were further evaluated.
      Finally, FSA > 1 was determined as the cut-off to indicate the degree of
      pulmonary fissure completeness and involved into a multivariate logistic
      regression model to identify the predictors for PCCs. RESULTS: In total, 528
      patients with Stage I to Stage II non-small-cell lung cancer were enrolled. There
      were 343 patients with 0 <= FSA <= 1, 105 patients with 1 < FSA <= 2 and 80
      patients with 2 < FSA <= 3. Pulmonary complication rate in patients with 1 < FSA
      <= 2 (25.7% vs 14.3%; P = 0.006) and with 2 < FSA <= 3 (33.8% vs 14.3%; P <
      0.001) was significantly higher than that in patients with 0 <= FSA <= 1. No
      difference was found in cardiovascular complication rate between these groups (P
      = 0.22). The Kaplan-Meier analysis showed that the length of hospital stay and
      the length of chest tube drainage in patients with 1 < FSA <= 2 and with 2 < FSA
      <= 3 were significantly longer than those in patients with 0 <= FSA <= 1.
      Incomplete pulmonary fissure (FSA > 1) was a strong independent predictor for
      PCCs (odds ratio = 2.12; P = 0.002) in the multivariate analysis. CONCLUSIONS:
      The degree of pulmonary fissure completeness can predict the PCCs and the length
      of hospital stay following video-assisted thoracoscopic surgery lobectomy for
      early-stage non-small-cell lung cancer.

PMID- 29049747
TI  - Bioethics Panels Open Door Slightly to Germline Gene Editing.

PMID- 29049748
TI  - Transfusion and blood stream infections after coronary surgery.
AB  - The aim of this study was to evaluate the impact of blood transfusion on
      bloodstream infections. This study included 2764 patients who underwent isolated
      coronary artery bypass grafting. Blood cultures were drawn in 27.9% of patients
      and were positive in 3.5% of them. Blood transfusion before blood cultures were
      drawn (4.7% vs 1.2%, odds ratio 3.75, 95% confidence interval 1.11-12.67) and
      deep sternal wound infection/mediastinitis (20.0% vs 2.8%, odds ratio 7.43, 95%
      confidence interval 2.72-20.32) were independent predictors of a positive
      postoperative blood culture. Positive blood culture increased the risk of 5-year
      mortality (among patients with blood cultures drawn: 44.7% vs 19.6%, adjusted
      hazard ratio 2.10, 95% confidence interval 1.18-3.71). Exposure to blood products
      may increase the risk of bloodstream infection after cardiac surgery. Positive
      blood cultures after coronary artery bypass grafting are associated with poor
      late survival. These findings require validation in prospective studies.

PMID- 29049749
TI  - Transvalvular pressure gradients for different methods of mitral valve repair:
      only neochordoplasty achieves native valve gradients.
AB  - OBJECTIVES: Many surgical and interventional methods are available to restore
      patency for patients with degenerative severe mitral valve regurgitation. Leaflet
      resection and neochordoplasty, which both include ring annuloplasty, are the most
      frequently performed techniques for the repair of posterior mitral leaflet flail.
      It is unclear which technique results in the best haemodynamics. In this study,
      we investigated the effect of different mitral valve reconstruction techniques on
      mitral valve haemodynamics and diastolic transvalvular pressure gradient in an ex
      vivo porcine model. METHODS: Eight porcine mitral valves were tested under
      pulsatile flow conditions in an in vitro pulsatile flow loop for haemodynamic
      quantification. Severe acute posterior mitral leaflet flail was created by
      resecting the posterior marginal chorda. The acute mitral valve regurgitation was
      corrected using 4 different repair techniques, in each valve, in a strictly
      successive order: (i) neochordoplasty with polytetrafluoroethylene sutures alone
      and (ii) with ring annuloplasty, (iii) edge-to-edge repair and (iv) triangular
      leaflet resection, both with ring annuloplasty. Valve haemodynamics were measured
      and quantified for all valve configurations (native, rupture and each surgical
      reconstruction). The results were analysed using a validated statistical linear
      mixed model, and the P-values were calculated using a 2-sided Wald test. RESULTS:
      All surgical reconstruction techniques were able to sufficiently correct the
      acute mitral valve regurgitation. Neochordoplasty without ring annuloplasty was
      the only reconstruction technique that resulted in haemodynamic properties
      similar to the native mitral valve (P-values from 0.071 to 0.901). The diastolic
      transvalvular gradient remained within the physiological range for all
      reconstructions but was significantly higher than in the native valve for
      neochordoplasty with ring annuloplasty (P < 0.000), edge-to-edge repair (P <
      0.000) and leaflet resection (P < 0.000). Neochordoplasty without ring
      annuloplasty resulted in a significantly better pressure gradient than
      neochordoplasty with a ring annuloplasty (P < 0.000). Additionally,
      neochordoplasty with a ring annuloplasty resulted in significantly lower
      transvalvular pressure gradients than edge-to-edge repair (P < 0.000) and leaflet
      resection (P < 0.000). CONCLUSIONS: Neochordoplasty with or without ring
      annuloplasty was the reconstruction technique that almost achieved native
      physiological haemodynamics after repair of posterior mitral leaflet flail after
      acute isolated chordal rupture in our ex vivo porcine model.

PMID- 29049750
TI  - Spontaneous intra-abdominal haemorrhage due to segmental arterial mediolysis
      following oesophagocolojejunostomy.
AB  - Segmental arterial mediolysis is a rare vascular disease that leads to
      spontaneous intra-abdominal haemorrhage, which causes shock and bowel ischaemia,
      and is associated with a high mortality rate. Here, we present a case of
      spontaneous intra-abdominal haemorrhage due to segmental arterial mediolysis in a
      patient who underwent oesophagocolojejunostomy for synchronous triple primary
      cancer, which was treated successfully by coil embolization. We conclude that a
      preoperative angiogram is necessary to detect vascular abnormalities, and in
      cases with severe haemorrhage, an urgent endovascular procedure is the treatment
      of choice.

PMID- 29049751
TI  - Hope as a Predictor of Anxiety and Depressive Symptoms Following Pediatric Cancer
      Diagnosis.
AB  - Objective: To examine hope and its components of agency and pathways as
      predictors of anxiety and depressive symptoms in children receiving cancer
      treatment. Methods: Sixty patients (mean standard deviation age = 13.3 (2.7); 57%
      male) completed Snyder's Hope Scales, the Children's Depression Inventory, and
      the State-Trait Anxiety Inventory at diagnosis and 3 month intervals for 1 year
      following pediatric cancer diagnosis. Parents also completed Snyder's Hope
      Scales. Linear mixed-effect regression was used to assess hope's role in
      longitudinal models of symptoms of depression and anxiety. Results: Agency was a
      significant predictor of between-patient differences and within-patient changes
      in symptoms of depression and anxiety. Neither patient pathways nor either
      component of parent hope was predictive of symptoms of depression or anxiety.
      Patients who were more likely to have depressive symptoms at baseline were older,
      diagnosed with leukemia, and non-Hispanic White as opposed to Hispanic. Patient
      demographics were not predictive of anxiety. Conclusions: Patient agency is a
      potential target for intervention to prevent or reduce anxiety and depressive
      symptoms following pediatric cancer diagnosis.

PMID- 29049753
TI  - Erratum.

PMID- 29049752
TI  - Cytomegalovirus infection in living-donor and cadaveric lung transplantations.
AB  - OBJECTIVES: Cytomegalovirus (CMV) infection remains a major cause of morbidity
      after lung transplantation. Some studies have reported prognostic factors for the
      postoperative development of CMV infection in cadaveric lung transplantation
      (CLT), but no research has been performed in living-donor lobar lung
      transplantation (LDLLT). Therefore, we analysed the possible risk factors of post
      transplant CMV infection and the differences between LDLLT and CLT. METHODS: The
      development of CMV disease and viraemia in 110 patients undergoing lung
      transplantation at Kyoto University Hospital in 2008-2015 were retrospectively
      assessed. The prognostic factors in the development of CMV infection and the
      differences between LDLLT and CLT were analysed. RESULTS: Among 110 patients, 58
      LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and
      viraemia were 92.0% and 58.5%, respectively. There was no difference in the
      development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P =
      0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV
      immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and
      R-D- recipients (recipient: negative, donor: negative) tended to have higher and
      lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34
      and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive).
      Significantly lower cumulative incidence of CMV viraemia was observed in patients
      receiving 12-month prophylactic medication (70.6% vs 36.8%, P < 0.001). Twenty
      eight patients (25.5%) had early cessation of anti-CMV prophylaxis due to
      toxicity; however, the extended prophylaxis duration did not increase the
      incidence of early cessation (P = 0.88). These trends were seen in both LDLLT and
      CLT. CONCLUSIONS: We found that there was no difference in the development of CMV
      infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides
      beneficial effect without increased toxicity also in LDLLT.

PMID- 29049754
TI  - Management of retrograde intraoperative Type A aortic dissection from descending
      thoracic aortic injury.
AB  - Intraoperative Type A aortic dissection during cardiothoracic surgery is
      extremely rare, but the consequences can be fatal. We report 2 case summaries of
      retrograde intraoperative Type A aortic dissection from descending thoracic
      aortic injury during ascending aortic cannulation and provide a discussion on
      management.

PMID- 29049755
TI  - Is ministernotomy superior to right anterior minithoracotomy in minimally
      invasive aortic valve replacement?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether, in patients undergoing minimally invasive aortic
      valve replacement (AVR), right anterior thoracotomy (RT) or mini-sternotomy (MS)
      was superior in terms of postoperative outcome? A total of 840 publications were
      found using the reported search. Of these, 6 represented the best available
      evidence to answer the clinical question. The authors, journal, date and country
      of publication, patient group studied, study type, relevant outcomes and results
      of these papers are tabulated. In all, except 1 study, the primary outcome was
      early mortality, ranging from in-hospital mortality to 90 days postoperatively.
      The remaining study was a cost-benefit analysis. Four studies were non-randomized
      observational studies, one of which was multicentre. Two were meta-analyses of
      studies comparing minithoracotomy or MS with conventional sternotomy for AVR,
      rather than direct comparisons of the 2 minimal access techniques. We conclude
      that there is a lack of high-quality evidence comparing RT and MS for minimally
      invasive AVR, with no randomized controlled trials to date. The available
      evidence shows no difference in early mortality between RT and MS for surgical
      AVR. In studies that directly compared RT and MS, RT was found to be associated
      with reduced length of hospital stay, despite longer cardiopulmonary bypass times
      and cross-clamp times. One study reported groin complications (10.8%) with the RT
      group, where peripheral cannulation was used, while the other 5 studies did not
      comment on groin complications associated with peripheral cannulation. In the
      only cost-benefit analysis, RT was found to carry considerably more cost than MS
      over and above conventional AVR.

PMID- 29049757
TI  - Guideline: An expert panel strongly recommends against arthroscopic knee surgery
      for degenerative knee disease.

PMID- 29049756
TI  - Interventions to Improve Follow-up of Positive Results on Fecal Blood Tests: A
      Systematic Review.
AB  - Background: Fecal immunochemical testing is the most commonly used method for
      colorectal cancer screening worldwide. However, its effectiveness is frequently
      undermined by failure to obtain follow-up colonoscopy after positive test
      results. Purpose: To evaluate interventions to improve rates of follow-up
      colonoscopy for adults after a positive result on a fecal test (guaiac or
      immunochemical). Data Sources: English-language studies from the Cochrane Central
      Register of Controlled Trials, PubMed, and Embase from database inception through
      June 2017. Study Selection: Randomized and nonrandomized studies reporting an
      intervention for colonoscopy follow-up of asymptomatic adults with positive fecal
      test results. Data Extraction: Two reviewers independently extracted data and
      ranked study quality; 2 rated overall strength of evidence for each category of
      study type. Data Synthesis: Twenty-three studies were eligible for analysis,
      including 7 randomized and 16 nonrandomized studies. Three were at low risk of
      bias. Eleven studies described patient-level interventions (changes to
      invitation, provision of results or follow-up appointments, and patient
      navigators), 5 provider-level interventions (reminders or performance data), and
      7 system-level interventions (automated referral, precolonoscopy telephone calls,
      patient registries, and quality improvement efforts). Moderate evidence supported
      patient navigators and provider reminders or performance data. Evidence for
      system-level interventions was low. Seventeen studies reported the proportion of
      test-positive patients who completed colonoscopy compared with a control
      population, with absolute differences of -7.4 percentage points (95% CI, -19 to
      4.3 percentage points) to 25 percentage points (CI, 14 to 35 percentage points).
      Limitation: More than half of studies were at high or very high risk of bias;
      heterogeneous study designs and characteristics precluded meta-analysis.
      Conclusion: Patient navigators and giving providers reminders or performance data
      may help improve colonoscopy rates of asymptomatic adults with positive fecal
      blood test results. Current evidence about useful system-level interventions is
      scant and insufficient. Primary Funding Source: National Cancer Institute.
      (PROSPERO: CRD42016048286).

PMID- 29049758
TI  - In small skin abscesses, clindamycin or trimethoprim-sulfamethoxazole after
      incision and drainage increased cures.

PMID- 29049759
TI  - Adding trimethoprim-sulfamethoxazole to cephalexin did not increase clinical cure
      in uncomplicated cellulitis.

PMID- 29049760
TI  - Triple therapy reduced mortality more than oseltamivir alone in patients admitted
      for severe influenza infection.

PMID- 29049761
TI  - Azithromycin reduced exacerbations and improved QoL in symptomatic asthma despite
      inhaled maintenance therapy.

PMID- 29049762
TI  - In severe asthma, benralizumab reduced daily oral glucocorticoid dose and asthma
      exacerbations at 6 months.

PMID- 29049763
TI  - Review: In adult inpatients with mild or moderate acute pancreatitis, early
      feeding may reduce length of stay.

PMID- 29049764
TI  - Pooled RCTs: In symptomatic carotid stenosis, endarterectomy had lower
      periprocedural risk than stenting.

PMID- 29049765
TI  - Self-monitoring of blood glucose did not improve HbA1c or QoL at 1 year in non
      insulin-treated type 2 diabetes.

PMID- 29049766
TI  - Review: In diabetes, intensive and standard glycemic control do not differ for
      end-stage kidney disease or death.

PMID- 29049767
TI  - The Relationship of Obesity to Hospice Use and Expenditures.

PMID- 29049769
TI  - Accuracy of Heart Rate Monitoring by Some Wrist-Worn Activity Trackers.

PMID- 29049768
TI  - The Relationship of Obesity to Hospice Use and Expenditures.

PMID- 29049770
TI  - Accuracy of Heart Rate Monitoring by Some Wrist-Worn Activity Trackers.

PMID- 29049771
TI  - Nonpharmacologic Therapies for Low Back Pain.

PMID- 29049772
TI  - Nonpharmacologic Therapies for Low Back Pain.

PMID- 29049773
TI  - On Continuity.

PMID- 29049774
TI  - Compassion.

PMID- 29049775
TI  - Heart in Hand.

PMID- 29049777
TI  - Web Exclusives. Annals Consult Guys - Mythbuster: Preoperative Blood Pressure
      Control.

PMID- 29049776
TI  - Web Exclusives. Annals for Hospitalists Inpatient Notes - Diagnostic Excellence
      Starts With an Incessant Watch.

PMID- 29049780
TI  - Video-assisted thoracic surgery is associated with better short-term outcomes
      than open thoracotomy in adult patients with intralobar pulmonary sequestration.
AB  - OBJECTIVES: This study was aimed to investigate potential benefits of
      thoracoscopic surgery for intralobar pulmonary sequestration in adult patients in
      terms of short-term surgical outcomes when compared with open surgery. METHODS:
      Data of 110 consecutive adult patients undergoing thoracoscopic surgery or open
      surgery for intralobar sequestration from January 2000 to December 2015 at our
      institution were reviewed. A total of 42 video-assisted thoracic surgery cases
      and 68 open surgery cases were identified. Perioperative outcomes were compared
      between video-assisted thoracic surgery and open surgery to evaluate efficacy.
      RESULTS: Neither group had surgical mortality. Although the overall morbidity was
      without statistical significance (P = 0.13), pleural effusion that required
      repeated thoracentesis was less frequent in thoracoscopic surgery (n = 1, 2.4% vs
      n = 11, 16.2%, P = 0.028). Thoracoscopic surgery was associated with less
      intraoperative bleeding [193 (standard deviation, SD 238) ml vs 241 (SD 221) ml,
      P = 0.013] and shorter postoperative stay [5.0 (SD 2.4) days vs 9.5 (SD 3.7)
      days, P < 0.001] compared with open thoracotomy. No significant difference was
      found for operation duration (P = 0.51) or chest drainage days (P = 0.11).
      CONCLUSIONS: Video-assisted thoracic surgery is associated with less
      intraoperative bleeding and shorter postoperative hospital stay than is open
      thoracotomy in surgical resection of intralobar pulmonary sequestration in adult
      patients.

PMID- 29049781
TI  - Does mitral valve repair matter in infants with ventricular septal defect
      combined with mitral regurgitation?
AB  - OBJECTIVES: This study aimed to assess mitral valve function after repair of
      ventricular septal defect (VSD) combined with mitral regurgitation (MR) in the
      mid-term follow-up period, to evaluate the clinical utility of simultaneous
      mitral valve repair (MVR). METHODS: From June 2005 to March 2014, 60 patients
      with VSD and MR underwent surgical treatment. After performing propensity score
      analysis (1:1) for the entire sample, 46 patients were selected and divided into
      2 groups: those with VSD closure and MVR (VSD + MVR, 23 patients) and those with
      VSD closure without mitral valve intervention (VSD only, 23 patients). The follow
      up period ranged from 12 to 48 months (median 32 months; interquartile range 28
      40 months). RESULTS: There was no postoperative mortality in either group. There
      was no significant difference in the duration of the postoperative period between
      groups (ventilation time, P = 0.49; inotropic support, P = 0.50). Mean
      cardiopulmonary bypass time and aortic cross-clamping time were significantly
      longer in the 'VSD + MVR' group (cardiopulmonary bypass, P = 0.023; aortic cross
      clamp, P < 0.001). There was no significant difference in regurgitation area (P =
      0.30) and MR grade (P = 0.76) between groups postoperatively. There was no
      significant difference in freedom from MR >= 2+ between groups (log-rank test, P
      = 0.28). In the 'VSD + MVR' group, 12-, 36- and 42-month freedom from MR >= 2+
      values were 100%, 59 +/- 10.4% [95% confidence interval (CI) 36.1-76.2%] and 44
      +/- 15% (95% CI 15.8-69.7%), respectively, while in the 'VSD only' group, these
      values were 100%, 54.5 +/- 10.6% (95% CI 32-72.3%) and 54.5 +/- 10.6% (95% CI 30
      72.3%), respectively. The only significant risk factor for recurrent MR >= 2+
      during the follow-up period was mild residual MR in the early postoperative
      period (P = 0.037). CONCLUSIONS: In infants with VSD combined with MR,
      simultaneous MVR has no benefits simultaneous MVR provided no advantage over that
      of isolated VSD closure. We found that the presence of mild residual MR in the
      early postoperative period predisposes the development of MR >= 2+ in follow-up
      period.

PMID- 29049783
TI  - Prognostic effect of incompletely lobulated fissures in p-Stage I non-small-cell
      lung cancer.
AB  - OBJECTIVES: Division of incompletely lobulated fissures is often performed during
      surgical resection of non-small-cell lung cancer (NSCLC); however, the effect of
      lobulation on tumour recurrence is unclear. This study aimed to assess the
      prognostic effect of lobulation in patients with NSCLC according to their
      preoperative and operative findings. METHODS: A retrospective study of patients
      with p-stage I NSCLC who underwent lobectomy was conducted between April 2008 and
      April 2016. A receiver operating characteristic curve of the number of stapling
      cartridges was constructed to determine the optimal cut-off value. Patients who
      underwent division of the interlobar fissure using 2 or more stapling cartridges
      (H group) were compared with those who did not undergo division of the interlobar
      fissure or who underwent division of the interlobar fissure using only 1
      cartridge (L group). RESULTS: The study included 85 patients, and of these
      patients, 46 were included in the L group and 39 in the H group. Survival
      analysis showed better disease-specific survival (P = 0.0135) and disease-free
      survival (P = 0.0412) in the L group. Cox regression analysis showed better
      disease-specific survival in patients who underwent division of the interlobar
      fissure with few stapler cartridges than in those who underwent division with
      more stapler cartridges (P = 0.021). CONCLUSIONS: The extent and status of
      incompletely lobulated fissures are significant risk factors for disease-specific
      survival in patients with resected p-stage I NSCLC.

PMID- 29049784
TI  - Hormonal manipulation after surgery for catamenial pneumothorax.
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was whether hormonal manipulation with
      gonadotrophin-releasing hormone analogues reduces the risk of recurrent
      catamenial pneumothorax after surgery, compared with surgery alone. Altogether
      819 papers were found using the reported search, of which 7 represented the best
      evidence to answer the clinical question. The authors, date, journal, country of
      publication, study type, level of evidence, patient group studied, relevant
      outcomes and results of these papers are tabulated. Of the 7 papers selected, 6
      demonstrated a reduction in recurrence of catamenial pneumothorax with the use of
      gonadotrophin-releasing hormone analogues, whereas in the single paper where
      surgery alone was performed, no evidence of recurrence was demonstrated. We
      therefore conclude that, based on very small retrospective observational studies,
      gonadotrophin-releasing hormone analogues used as an adjunct to surgical
      intervention may reduce the risk of recurrent pneumothorax, when compared with
      either no hormonal therapy or oestrogen-progesterone therapy, but should be
      initiated and supervised by gynaecologists who will be familiar with the therapy
      and the potential side effects.

PMID- 29049782
TI  - Rotational speed modulation used with continuous-flow left ventricular assist
      device provides good pulsatility.
AB  - OBJECTIVES: Continuous-flow left ventricular assist devices (CF-LVADs) are widely
      used to treat patients with end-stage heart failure. Although continuous flow is
      different from physiological flow, patients show improved outcomes after CF-LVAD
      implantation. A novel rotational speed (RS) modulation system used with CF-LVAD
      (EVAHEART) has been developed, which can change RS in synchronization with the
      native cardiac cycle. We conducted the present study to investigate the influence
      of the system on pulsatility in peripheral perfusion. METHODS: We implanted
      EVAHEART devices at the left ventricular apex drainage and the descending aortic
      perfusion via a left thoracotomy in 7 adult goats (56.8 +/- 8.1 kg). Cardiogenic
      shock was induced by a beta-adrenergic antagonist. We evaluated the pulsatility
      index and maximal time derivative of flow rate (max dQ/dt) of the carotid,
      mesenteric and renal arteries. These data were collected with a bypass rate of
      100% under 4 conditions: circuit clamp, continuous mode, co-pulse mode (increased
      RS during systole) and counter-pulse mode (increased RS during diastole).
      RESULTS: The pulsatility indexes of the carotid and renal artery in the co-pulse
      mode were significantly higher than in the other modes. Max dQ/dt of the carotid
      and mesenteric arteries were significantly higher in the co-pulse mode than in
      the counter-pulse mode. CONCLUSIONS: The co-pulse mode of this novel RS
      modulation system may provide better pulsatility not only in the large vessels
      but also in the peripheral vasculature.

PMID- 29049785
TI  - A surprise aberrant pulmonary vein.
AB  - We report an incidental discovery of the superior pulmonary vein coming from a
      strange anatomical location when performing a robotic left lower lobectomy. When
      trying to identify the superior pulmonary vein, an aberrant pulmonary vein was
      found leading into the innominate vein.

PMID- 29049786
TI  - Three-dimensional versus two-dimensional video-assisted thoracic surgery for
      thoracic disease: a meta-analysis.
AB  - OBJECTIVES: It remains unclear whether 3D systems are manoeuvrable in video
      assisted thoracic surgery (VATS) for patients with thoracic diseases. The
      objective of this systematic review and meta-analysis was to evaluate the
      efficacy and safety of 3D VATS compared with 2D VATS. METHODS: A systemic
      research of the literature was performed using the PubMed, Embase, the Cochrane
      library, China National Knowledge Infrastructure, Wanfang and CQVIP databases
      through December 2016. Studies investigating the efficacy and safety of 3D VATS
      compared with 2D VATS were eligible for our meta-analysis. Odds ratios and mean
      differences or standard mean differences with 95% confidence intervals (95% CI)
      as well as a P-value were applied to compare continuous and dichotomous
      variables, respectively. RESULTS: Seven studies with 1080 patients (525 patients
      for 3D VATS and 555 patients for 2D VATS) were included. There were significant
      differences in the 3D group with regard to shorter operation times (standard mean
      difference = -0.66, 95% CI: -0.98 to - 0.34; P < 0.001), less blood loss (mean
      difference = -12.12, 95% CI: -19.07 to - 5.16; P < 0.001) and shorter
      postoperative drainage times (standard mean difference = -0.53, 95% CI: -0.92 to 
      0.14; P = 0.008) compared with the 2D group. However, no statistical difference
      was found for postoperative hospital stay, total postoperative drainage volume,
      postoperative drainage volume in 24 h, number of lymph nodes dissected and
      postoperative complications. CONCLUSIONS: The results of this systematic review
      and meta-analysis suggest that 3D VATS might be an acceptable method for treating
      thoracic diseases in the future.

PMID- 29049787
TI  - Sutureless aortic valve replacement versus transcatheter aortic valve
      implantation: a meta-analysis of comparative matched studies using propensity
      score matching.
AB  - OBJECTIVES: The aim of this meta-analysis was to compare outcomes of patients
      undergoing transcatheter aortic valve implantation (TAVI) with those undergoing
      surgical aortic valve replacement using sutureless valves. METHODS: A systematic
      review and meta-analysis in accordance with the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) statement was performed. RESULTS:
      No randomized controlled trials were identified. Six comparative studies using
      propensity score matching met the inclusion criteria. This meta-analysis
      identified 1462 patients in that 731 patients underwent surgical aortic valve
      replacement using sutureless valves (SU) and 731 patients underwent a TAVI. The
      30-day or in-hospital mortality was lower in the SU group [odds ratio (OR) 0.54,
      95% confidence interval (CI) 0.36-0.80; P = 0.003]. In the TAVI group, the
      incidence of postoperative stroke was higher (OR 0.36, 95% CI 0.17-0.79; P =
      0.01). The incidence of moderate or severe paravalvular regurgitation was higher
      in the TAVI group (OR 0.22, 95% CI 0.14-0.35; P = 0.001). There were neither
      differences in the postoperative renal failure (OR 1.44, 95% CI 0.46-4.58; P =
      0.53) nor in the number of patients requiring postoperative pacemaker
      implantation (OR 1.06, 95% CI 0.54-2.08; P = 0.86). Patients in the SU group
      required more transfusions (OR 4.47, 95% CI 2.77-7.21; P = 0.0001), whereas those
      in the TAVI group had higher major vascular complications (OR 0.06, 95% CI 0.01
      0.25; P = 0.0001). Intensive care unit stay was not different (mean difference
      0.99, 95% CI - 1.22 to 1.40; P = 0.53). One-year survival was better in the SU
      group (Peto OR 0.35, 95% CI 0.18-0.67; P = 0.001), as was the 2-year survival
      (Peto OR 0.38, 95% CI 0.17-0.86; P = 0.001). CONCLUSIONS: Surgical aortic valve
      replacement using sutureless valves is associated with better early and mid-term
      outcomes compared with TAVI in high- or intermediate-risk patients.

PMID- 29049788
TI  - Full metal jacket: transfemoral aortic valve implantation for regurgitant valve
      after endovascular aortic repair.
AB  - Transfemoral aortic valve implantation has become an almost routine
      interventional procedure for severe aortic stenosis in high-risk patients. Over
      time an increased number of experiences has led to unusual procedures. In this
      report, we present a successful valve-in-valve transfemoral aortic valve
      implantation in a patient with aortic regurgitation, who previously had
      debranching and thoracic endovascular aortic repair operations.

PMID- 29049789
TI  - Epidermal growth factor receptor mutation status is strongly associated with
      smoking status in patients undergoing surgical resection for lung adenocarcinoma.
AB  - OBJECTIVES: The purpose of this analysis was to examine the relationship between
      epidermal growth factor receptor (EGFR) mutation status and clinicopathological
      factors in a cohort of patients who underwent surgical resections for lung
      adenocarcinoma. METHODS: From the patients who underwent surgical resections for
      primary lung cancers between 2005 and 2012, 371 consecutive adenocarcinoma
      patients were enrolled in this study, and their tumours were analysed for EGFR
      mutations. We examined the clinicopathological factors of all enrolled patients,
      including age, sex, pathological stage and smoking status and tested for
      associations with EGFR mutation status. RESULTS: Among the 371 enrolled patients,
      195 (52%) patients had EGFR mutations. There were significantly more women, never
      smokers and tumours of lower grade histology in the EGFR mutation group than in
      the wild-type group (P < 0.001 each). However, other factors, such as
      pathological stage and World Health Organization classification, were not
      significantly associated with mutation status. Multivariable analysis showed that
      age, smoking history and histological grade were independently associated with
      EGFR mutations (P = 0.026, P < 0.001 and P < 0.001, respectively), but sex was
      not. Regarding smoking status, especially, frequency of EGFR mutation decreased,
      as smoking index increased. On the other hand, sex and smoking cessation (whether
      the patients were former or current smokers) were not significantly associated
      with EGFR mutation status. CONCLUSIONS: In our cohort of patients who underwent
      surgical resection for lung adenocarcinoma, EGFR mutation status was strongly
      associated with smoking status, especially smoking index.

PMID- 29049790
TI  - Sinus of Valsalva aneurysms with concomitant aortic insufficiency: how should the
      aortic valve be managed?
AB  - OBJECTIVES: Sinus of Valsalva aneurysms (SVAs) are rare and are often complicated
      by aortic insufficiency (AI). Treating AI is important for achieving good long
      term results in patients with SVA. Here, we have summarized our experience with
      the surgical management of patients with SVA with concomitant AI. METHODS:
      Patients who were diagnosed with SVA and underwent surgical treatment between
      January 2008 and May 2016 were included. Clinical characteristics, including age,
      gender, SVA anatomy and concurrent anomalies, were analysed. The surgical
      strategies, intraoperative results and early and late outcomes were evaluated.
      RESULTS: A total of 178 patients (age 37.4 +/- 13.1 years, 114 men) were
      identified. Eighty-seven (48.9%) patients had at least 2+ AI preoperatively.
      Patients with AI had a significant higher incidence of right coronary SVA with
      concomitant ventricular septal defects (80.5% vs 54.9%, P < 0.001). Concurrent
      aortic valve surgery was performed in 70 patients with 63 valve replacements and
      7 valve repairs. The other 17 patients underwent SVA repair only. The mean follow
      up time was 44.4 +/- 33.8 months. During the follow-up, no patients who underwent
      valve replacement experienced perivalvular leakage, whereas 7 patients who
      underwent aortic valve repair had trivial-to-mild AI and 3 of the 17 patients who
      underwent SVA repair only presented with moderate AI. CONCLUSIONS: Various
      surgical techniques can be utilized to manage concomitant AI without compromising
      short-term outcomes. Valve replacement yields good long-term results. According
      to our experience, valve repair, especially valve-sparing procedures performed by
      experienced surgeons, could be an acceptable option when managing concomitant AI
      in young patients.

PMID- 29049792
TI  - Featured Article: Psychosocial and Family Functioning Among Latino Youth With
      Spina Bifida.
AB  - Objective: This study examined differences in psychosocial and family functioning
      between Latino and non-Latino Caucasian youth with spina bifida (SB), and
      examined family functioning as a predictor of youth psychosocial functioning as
      moderated by ethnicity. Methods: Participants were part of a larger, longitudinal
      study (Devine, Holbein, Psihogios, Amaro, & Holmbeck, 2012) and included 74 non
      Latino Caucasian youth with SB and 39 Latino youth with SB (M age = 11.53, 52.2%
      female). Data were collected at Time 1 and 2 years later, and included
      questionnaire and observational data of psychosocial and family functioning.
      Results: Latino youth demonstrated fewer externalizing symptoms, less family
      conflict, but also less social competence. Family conflict was associated with
      psychosocial functioning in Latino youth, while family cohesion, conflict, and
      stress were associated with psychosocial functioning in non-Latino Caucasian
      youth. Conclusions: Psychosocial and family functioning, and their relationship
      over time, may be different in Latino versus Caucasian youth with SB.

PMID- 29049793
TI  - Triangular resection versus neochordal replacement for posterior leaflet
      prolapse: a morphological assessment.
AB  - OBJECTIVES: To evaluate the morphological reconstruction as assessed by 3D
      transoesophageal echocardiography after triangular resection and neochordal
      replacement in the treatment of posterior leaflet prolapse. METHODS: We
      retrospectively selected 46 patients with isolated posterior leaflet prolapse who
      were undergoing mitral valve repair using triangular resection (n = 20) and
      neochordal replacement (n = 26) techniques. Sixty patients without valvular heart
      disease were also included as the control group. Thorough 3D transoesophageal
      echocardiography inspections were performed for the entire cohort, and
      morphological parameters of mitral valve complex were measured and compared. Mid
      term repair durability was followed up by transthoracic echocardiography.
      RESULTS: The baseline parameters, including annular size, leaflet tenting,
      leaflet area, coaptation line lengths and aortomitral angle, were significantly
      larger in prolapsed valves. After repair, tenting volume, exposed posterior
      leaflet area and coaptation line lengths were restored to the normal range.
      Baseline clinical characteristics and 3D transoesophageal echocardiography
      parameters were comparable in patients treated with 2 techniques, and all
      parameters remained comparable between the resection and the non-resection groups
      after repair, except for exposed posterior leaflet area and posterior leaflet
      ratio. At 62.2 +/- 18.5 months after surgery, degrees of residual regurgitation
      were similar between 2 techniques. CONCLUSIONS: Triangular resection and
      neochordal replacement can achieve comparable restoration to structural normality
      and functional competency of mitral valves with posterior leaflet prolapse.
      Resection of prolapsed segment does not significantly affect coaptation geometry
      but instead may aid in achieving normal posterior leaflet ratio.

PMID- 29049791
TI  - The Stability and Influence of Barriers to Medication Adherence on Seizure
      Outcomes and Adherence in Children With Epilepsy Over 2 Years.
AB  - Objective: To determine the stability and influence of adherence barriers on
      medication adherence and seizure control in pediatric epilepsy. Methods:
      Caregivers of 118 children aged 2-12 years old with epilepsy completed the
      Pediatric Epilepsy Medication Self-Management Questionnaire at nine time points
      over 2 years post diagnosis. Electronically monitored antiepileptic drug
      adherence and seizure outcome data were collected. Results: Hierarchical linear
      modeling results for overall barriers remained stable over 2 years. Specific item
      level barriers were also generally stable over time, with the exception of
      running out of medication becoming more of a barrier over time. No specific
      barriers were related to seizure control; however, difficulties swallowing
      medication, forgetting, and medication refusal were related to electronically
      monitored adherence over time. Conclusions: Assessing for specific adherence
      barriers over time may lead to identification of interventions that result in
      improved adherence and care.

PMID- 29049794
TI  - A novel approach to treating a post-sternotomy internal mammary artery
      pseudoaneurysm.
AB  - Pseudoaneurysms of the internal mammary artery are a rare complication of median
      sternotomy. They may clinically present as a pulsatile mass or with signs of
      rupture and haemodynamic instability. In stable patients, percutaneous thrombin
      injection of the pseudoaneurysm is a safe and minimally invasive procedure to
      treat the pseudoaneurysm and avoid further surgery. We present a case of a
      pseudoaneurysm of a branch of the right internal mammary artery post-median
      sternotomy with no signs or symptoms of haemodynamic instability. The
      pseudoaneurysm was successfully treated with ultrasound-guided percutaneous
      thrombin injection.

PMID- 29049795
TI  - Establishing stable innominate access by inserting a body floss wire from the
      brachial artery to the femoral artery facilitates right carotid artery stenting
      in Type III arch anatomy.
AB  - OBJECTIVES: In patients with severe carotid artery stenosis, the anatomy of their
      Type III aortic arch increases the difficulty and complication rates during
      carotid artery stenting because of its tortuosity and sharp angulation for
      cannulation as well as the unstable support of the guidewire for shuttle sheath
      delivery. METHODS: We demonstrate a novel technique to overcome these challenges,
      namely the creation of stable innominate artery access by inserting a through-and
      through body floss wire from the right brachial artery to the femoral artery.
      RESULTS: We successfully performed right carotid artery stenting in 3 patients
      with Type III arch anatomy. All patients received regular outpatient follow-up
      uneventfully for more than 1 year. CONCLUSIONS: This facilitates the procedure of
      the right carotid artery stenting in patients with Type III aortic arch.

PMID- 29049797
TI  - Astrocyte elevated gene-1 is overexpressed in non-small-cell lung cancer and
      associated with increased tumour angiogenesis.
AB  - OBJECTIVES: Astrocyte elevated gene-1 (AEG-1) functions to mediate angiogenesis,
      and its upregulation is responsible for tumour angiogenesis during cancer
      development. This study analysed AEG-1 expression in non-small-cell lung cancer
      (NSCLC) for association with NSCLC clinicopathological features and tumour
      angiogenesis. METHODS: The expression of AEG-1, vascular endothelial growth
      factor and intratumoural microvessel density (assessed using the expression of
      CD105) was detected by immunohistochemistry in 88 paired tumour tissue and
      adjacent normal tissue specimens obtained from NSCLC patients. The Kaplan-Meier
      curves were used for survival analysis through an online tool
      (http://kmplot.com/analysis/). RESULTS: AEG-1 was overexpressed in 61.3% of NSCLC
      tissues vs 6.8% (6/88) of normal tissues (P < 0.001). AEG-1 expression in NSCLC
      was significantly associated with advanced pTNM stage (P = 0.021), tumour
      dedifferentiation (P = 0.034), vascular invasion (P = 0.035), lymph node
      metastasis (P < 0.001) and poor overall survival (P = 0.024). Moreover, the
      expression of AEG-1 in NSCLC was associated with tumour angiogenesis; that is,
      vascular endothelial growth factor overexpression (P < 0.001) and intratumoural
      microvessel density (P < 0.001). CONCLUSIONS: This study demonstrates that AEG-1
      expression is associated with NSCLC development, angiogenesis, progression and
      poor prognosis, indicating that the adjuvant therapy with antiangiogenic agent be
      adopted for the early postoperative period before the start of conventional
      chemotherapy in patients with AEG-1 overexpressed NSCLC.

PMID- 29049796
TI  - Surgical strategy for aortic arch reconstruction after the Norwood procedure
      based on numerical flow analysis.
AB  - OBJECTIVES: Inefficient aortic flow after the Norwood procedure is known to lead
      to the deterioration of ventricular function due to an increased cardiac
      workload. To prevent the progression of aortic arch obstruction, arch
      reconstruction concomitant with second-stage surgery is recommended. The aim of
      this study was to determine the indications for reconstruction based on numerical
      simulation and to reveal the morphology that affects the haemodynamic parameters.
      METHODS: Fifteen patients who underwent the Norwood procedure or arch repair and
      Damus-Kaye-Stansel anastomosis were enrolled. The pressure gradient in aortic
      arch was 1.6 +/- 3.9 mmHg (ranged from 0 to 12 mmHg) on catheter examination. Six
      patients who had prominent turbulent flow accompanied with a large flow energy
      loss index greater than 40 mW/m2 and high wall shear stress greater than 100 Pa
      underwent arch reconstruction. RESULTS: After arch reconstruction, the energy
      loss index significantly decreased from 88.5 +/- 50.0 mW/m2 to 23.1 +/- 10.4
      mW/m2 (P = 0.026) and wall shear stress significantly decreased from 194.5 +/-
      87.4 Pa to 60.3 +/- 40.5 Pa (P = 0.0062). There were 3 late deaths due to heart
      failure caused by progressive atrioventricular valve regurgitation during the
      follow-up period (60 months). The systemic ventricular function was preserved in
      the remaining patients without any pressure gradients in the arch. CONCLUSIONS:
      Determining the surgical strategy for arch reconstruction based on numerical flow
      analysis may effectively reduce the ventricular load even if no stenosis or
      pressure gradients are observed on catheter examination or echocardiography.

PMID- 29049798
TI  - Near-infrared fluorescence-guided thoracoscopic surgical intervention for
      postoperative chylothorax.
AB  - OBJECTIVES: Chylothorax is an infrequent but relatively serious complication
      after lung cancer surgery. Finding the leakage site and identifying the thoracic
      duct (TD) are the key points of surgical intervention for chylothorax. In this
      study, for the first time, we demonstrated near-infrared fluorescence imaging
      with indocyanine green (ICG) in video-assisted thoracoscopic surgery (VATS)
      intervention for chylothorax in humans. METHODS: This study included 4 patients
      diagnosed with chylothorax after lung cancer surgery who underwent VATS
      intervention; 0.2 mg/kg of ICG was injected subcutaneously into the bilateral
      inguinal region approximately 30 min before surgery. The D-light P(r) near
      infrared thoracoscope was used for intraoperative fluorescence imaging. RESULTS:
      All patients underwent VATS intervention on the right side. Chyle leakage points
      were detected at the point of dissection of the station of the 4R lymph node
      behind the azygos vein in 3 patients and at the adjacent point of prophylactic
      ligation of the TD in 1 patient. The fluorescent hotspot of ICG leakage was
      detected first. The signal-to-background ratio of the TD or chyle averaged 4.41
      (range 2.31-6.72). The TD fluorescent signals lasted for at least 1 h. With the
      guidance of real-time fluorescence lymphography, the fistulas and the main trunk
      of the TD were identified and double ligated. Small branches of the TD were
      occasionally detected and ligated. Chylothorax was managed successfully by
      surgical interventions in all patients. CONCLUSIONS: Near-infrared fluorescence
      imaging with ICG provided highly sensitive and real-time imaging of the TD in
      VATS intervention for chylothorax in humans. Clinical registration number:
      NCT02611245.

PMID- 29049799
TI  - Neurological outcome and efficacy of intensive craniocervical screening for
      elective cardiac surgery.
AB  - OBJECTIVES: To evaluate the efficacy of intensive craniocervical screening before
      elective cardiovascular surgery. METHODS: A retrospective analysis of 1134
      consecutive patients who underwent routine screening before cardiovascular
      surgery between November 2004 and December 2014 was conducted. The study was
      divided into 2 distinct cohorts of patients undergoing surgery: before (n = 500)
      and after (n = 634) the introduction of intensive screening in January 2009. In
      2009, preoperative screening underwent a transition from the evaluation of
      carotid atherosclerosis alone to that of craniocervical atherosclerosis.
      Additionally, patients with moderate or greater stenosis on intensive screening
      underwent single-photon emission computed tomography with acetazolamide.
      Craniocervical atherosclerosis was classified as no or mild [0-49%: n = 836
      (before/after: 370/466)], moderate [50-69%: n = 118 (56/62)] or severe [70-100%:
      n = 141 (36/105)]. One of 166 (0.6%) patients with moderate or greater stenosis
      undergoing single-photon emission computed tomography with acetazolamide after
      the introduction of intensive screening was diagnosed as having impaired cerebral
      autoregulation. RESULTS: The occurrences of perioperative stroke were 2.8% before
      the introduction of intensive screening and 0.9% after that (P = 0.033). Notably,
      intraoperative stroke significantly decreased from 1.4% to 0.2% (P = 0.034).
      Specifically, the occurrence of perioperative stroke in patients with no or mild
      stenosis decreased significantly after the introduction of intensive screening,
      from 2.7% to 0.4% (P = 0.007). CONCLUSIONS: The incidence of perioperative stroke
      decreased following the introduction of intensive screening. Intensive screening
      may be able to detect patients with a greater risk of perioperative stroke.

PMID- 29049800
TI  - Ex utero intrapartum treatment-to-extracorporeal membrane oxygenation followed by
      cardiac operation for truncus arteriosus communis.
AB  - Extracorporeal membrane oxygenation has been recently indicated as an ex utero
      intrapartum treatment procedure for placental support in patients with a large
      thoracic mass. In our case, a foetus with truncus arteriosus communis and hydrops
      with ventricular failure due to severe truncal valve stenosis was delivered under
      ex utero intrapartum treatment-to-extracorporeal membrane oxygenation at 34 weeks
      of gestation. The neonate underwent truncal valve plasty. He could be weaned off
      extracorporeal membrane oxygenation, but he died because of the infection on
      postnatal Day 24.

PMID- 29049802
TI  - The Bridge Occlusion Balloon as a safety net in a high-risk transvenous lead
      extraction procedure.
AB  - Injuries to the superior vena cava (SVC) during transvenous lead extraction (TLE)
      procedures are a rare but life-threatening complication. The Bridge Occlusion
      Balloon (BOB) is specifically designed for temporary SVC occlusion in TLE
      procedures. We report the first case of a 27-year-old man using the BOB as a
      safety net in a high-risk TLE procedure. This patient, with a congenitally
      corrected transposition of the great arteries and a third-degree atrioventricular
      block, presented with 4 dysfunctional pacemaker leads, venous stenosis and the
      necessity for a new pacemaker system. The leads were implanted for 10 and 19
      years. The BOB was placed with a radiopaque marker at the cavoatrial junction and
      was inflated with 46 ml of an 80/20 saline/contrast agent mixture. An angiography
      was performed to confirm SVC occlusion. With the deflated balloon in place, the
      TLE procedure with laser and mechanical sheaths was performed. Successful
      extraction of 2 dysfunctional leads, as well as venous recanalization, for the
      new right atrial and right ventricular lead implantation was achieved. We have
      shown the feasibility of using powered extraction sheaths with a deflated BOB in
      place. This allows for immediate balloon inflation, in case of an SVC
      perforation.

PMID- 29049801
TI  - Search for genetic factors in bicuspid aortic valve disease: ACTA2 mutations do
      not play a major role.
AB  - OBJECTIVES: Mutations in ACTA2 have been reported as a cause of familiar thoracic
      aortic aneurysm (TAA) with associated bicuspid aortic valve (BAV) in some
      individuals. Our aim is to investigate the role of ACTA2 mutations in BAV
      associated with TAA in 20 patients. METHODS: We recruited 20 patients who
      underwent surgery for BAV and TAA; clinical genetic evaluation and ACTA2 mutation
      analysis were performed on each patient, along with next-generation sequencing
      analysis of BAV-related genes. Available first-degree relatives were enrolled and
      evaluated with echocardiography and clinical genetic examination. RESULTS: No
      mutations were found in ACTA2 or in BAV-related genes in our probands nor any
      common clinical signs possibly related to their heart disease. One-third of
      probands did not have any cardiovascular risk factor. Surgery was required at a
      young age (mean age 47.2 years) and at relatively small ascending aortic
      diameters (mean size 49.7 mm). In 77 first-degree relatives, 1 new diagnosis of
      TAA requiring surgery was made and 8 previous BAV/TAA diagnoses (9/77 = 11.7%)
      were confirmed. The phenotype BAV +/- TAA segregated in 25% of our families.
      CONCLUSIONS: Although based on a small cohort, our results seemed to justify the
      conclusion that ACTA2 did not play a significant role in the pathogenesis of BAV
      aortopathy. The underlying genetic factors of this condition remain elusive and
      both large association studies and exome or genome sequencing could represent
      promising tools to unravel its pathogenesis. Aortic resection of TAA at elective
      surgery in these patients should be recommended as well as echocardiography in
      their first-degree relatives.

PMID- 29049803
TI  - Prognostic significance of immune-nutritional parameters for surgically resected
      elderly lung cancer patients: a multicentre retrospective study.
AB  - OBJECTIVES: The world's population is rapidly ageing, and the age of patients
      with lung cancer will increase as well. The prognostic nutritional index,
      controlling nutritional status and the geriatric nutritional risk index (GNRI)
      are useful parameters for evaluating immune-nutritional status. We aimed to
      perform a multicentre retrospective study to investigate the correlations of
      these immune-nutritional parameters with postoperative comorbidities or surgical
      outcomes of elderly patients with non-small-cell lung cancer (NSCLC). METHODS: We
      selected 272 consecutive patients with NSCLC aged >75 years treated from January
      2005 to December 2012 and evaluated 3 preoperative immune-nutritional parameters
      as potential predictive factors of postoperative comorbidities or as prognostic
      factors for surgically resected elderly patients with NSCLC. RESULTS: Prognostic
      nutritional index, GNRI, sex and preoperative respiratory comorbidities were
      significantly associated with postoperative comorbidities. Multivariate analyses
      revealed that preoperative GNRI, sex, preoperative serum carcinoembryonic antigen
      levels, preoperative serum cytokeratin 19 fragment levels, pathological N factor
      and pleural invasion were significantly associated with overall survival (OS).
      Abnormal GNRI was significantly associated with histology and outcomes. The
      Kaplan-Meier analysis of OS as a function of preoperative GNRI revealed that
      patients with an abnormal GNRI experienced significantly shorter OS compared with
      those with normal GNRI (5-year OS, 45.15% vs 64.10%, respectively; P = 0.0007,
      log-rank test). The controlling nutritional status score was not significantly
      associated with postoperative comorbidities or surgical outcomes. CONCLUSIONS:
      Preoperative GNRI is a novel preoperative predictor of postoperative
      comorbidities and a prognostic factor that may identify high-risk elderly
      patients with NSCLC.

PMID- 29049804
TI  - Preoperative statins as modifiers of cardiac and inflammatory outcomes following
      coronary artery bypass graft surgery: a meta-analysis.
AB  - Early postoperative cardiac complications of coronary artery bypass graft
      surgery, such as atrial fibrillation (AF) or myocardial infarction (MI), may be
      beneficially modulated by preoperative statins, involving their anti-inflammatory
      effects. There is uncertainty on the clinical merit of statin pretreatment.
      Addressing this, we conducted a meta-analysis of early cardiac complications and
      inflammatory markers following statin pretreatment in coronary artery bypass
      graft surgery. A search of Medline and Cochrane databases was undertaken to
      identify suitable studies. A meta-analysis was carried out for early cardiac (AF,
      MI, myocardial injury markers) and inflammatory (cytokines, C-reactive protein)
      outcomes. We identified 17 suitable studies that featured data from the total of
      2796 patients. Twelve studies (1260 treated and 1263 untreated patients) reported
      AF incidence. Statin pretreatment was associated with a significant decrease of
      AF incidence: odds ratio 0.44 (95% confidence interval: 0.27-0.70; P = 0.003).
      Seven studies (381 treated and 277 untreated patients) reported useful data on
      MI. Unlike in AF, no significant modulation of postoperative MI in association
      with statin pretreatment could be observed: odds ratio 0.62 (95% confidence
      interval: 0.21-1.81; P = 0.62). Five studies (248 treated and 245 untreated
      patients) provided data on postoperative rise of C-reactive protein. This rise
      was significantly downregulated in statin-pretreated patients: standardized mean
      difference -0.44 (95% confidence interval: -0.78 to -0.11; P = 0.02). Thus,
      postoperative AF incidence is the biggest beneficiary of statin pretreatment in
      coronary artery bypass graft surgery. This effect is associated with beneficial
      modulation of systemic inflammatory markers.

PMID- 29049805
TI  - Health-Related Quality of Life in Pediatric Patients With Demyelinating Diseases:
      Relevance of Disability, Relapsing Presentation, and Fatigue.
AB  - Objective: Decreased health-related quality of life (HRQOL) in pediatric patients
      with multiple sclerosis is established, but little research has examined HRQOL in
      the broader pediatric demyelinating disease population, and predictors of reduced
      HRQOL are largely unexplored. We sought to (1) compare generic HRQOL and fatigue
      of pediatric patients with relapsing (i.e., multiple sclerosis and neuromyelitis
      optica) versus monophasic demyelinating diseases (i.e., acute disseminated
      encephalomyelitis, optic neuritis, transverse myelitis, clinically isolated
      syndrome) and (2) examine the extent to which disability, relapsing disease, and
      fatigue predict HRQOL. Methods: Child and/or parent-proxy reports of generic and
      fatigue-related HRQOL were collected for 64 pediatric patients with demyelinating
      diseases. HRQOL of the sample was compared with published healthy child norms.
      Independent samples t-tests compared HRQOL and fatigue for children with
      monophasic versus relapsing diseases. Regression analyses examined disability,
      disease presentation, and fatigue as potential predictors of HRQOL. Results:
      Compared with healthy child norms, generic HRQOL was significantly lower for the
      demyelinating disorder group, for both child and parent reports across multiple
      domains. As hypothesized, the relapsing disease group reported lower overall
      HRQOL and more fatigue than the monophasic group. Disability and relapsing
      disease predicted lower HRQOL for both parents and children, whereas fatigue was
      only predictive per the child perspective. Conclusions: Children with
      demyelinating diseases evidence significantly lower HRQOL than healthy peers,
      supporting need for intervention. Those with relapsing disease appear
      particularly at risk; targeting disability and fatigue may be fruitful areas for
      intervention.

PMID- 29049806
TI  - Results of treatment for thymic neuroendocrine tumours: multicentre
      clinicopathological study.
AB  - OBJECTIVES: A thymic neuroendocrine tumour (TNET) is rare, and few comprehensive
      reports of treatment results have been presented. To clarify the
      clinicopathological characteristics of TNET in affected patients, outcomes were
      retrospectively examined using cases accumulated in a multicentre survey.
      METHODS: Thirty patients (25 men and 5 women) who underwent surgical resection or
      biopsy procedures at 10 institutions of the Thoracic Surgery Study Group of Osaka
      University (TSSGO) between January 1986 and June 2015 and pathologically
      diagnosed with TNET were enrolled. RESULTS: The examined tumours were classified
      as typical carcinoid in 7 patients, atypical carcinoid in 11 patients, large-cell
      neuroendocrine carcinoma in 3 patients and small-cell carcinoma in 9 patients, of
      which 2 underwent surgical biopsy procedures and 28 surgical resection, with a
      macroscopic complete resection procedure performed in 27 patients. Induction
      therapy was performed in 2 patients and adjuvant therapy in 10 patients. Thirteen
      patients had recurrence, with distant metastasis, especially in bone and lung
      tissues, more frequent than local recurrence. Overall survival was 77% after 5
      years and 35% after 10 years, whereas relapse-free survival was 48% and 29%, and
      cancer-specific survival was 90% and 48%, respectively. Overall survival was
      significantly better in patients who underwent macroscopic complete resection (P
      = 0.010). As for relapse-free survival patients, TNM Stage I or II (P = 0.011)
      and received adjuvant therapy patients (P = 0.042) showed good survival rates.
      CONCLUSIONS: The prognosis of patients with TNET was favourable in those treated
      with macroscopic complete resection. Survival is promising even in patients with
      postoperative recurrence, following treatment utilized for pulmonary
      neuroendocrine tumour or gastroenteropancreatic neuroendocrine tumour.

PMID- 29049807
TI  - Impact of initial aortic diameter and false-lumen area ratio on Type B aortic
      dissection prognosis.
AB  - OBJECTIVES: Medical treatment is the gold standard for uncomplicated acute Type B
      aortic dissection (ATBAD). Although endovascular treatment could become an
      alternative therapy, it is unclear which ATBAD patients should undergo
      endovascular intervention. We aimed to evaluate the outcomes of patients with
      uncomplicated ATBAD and identify the risk factors for major adverse events.
      METHODS: We retrospectively reviewed 134 consecutive patients who underwent
      initial treatment for uncomplicated ATBAD between 2004 and 2015. Follow-up rate
      was 98.5%, and the median follow-up period was 47 months. We evaluated the
      incidence of major adverse events (aortic-related death, aortic surgery and
      dilated aorta >= 55 mm) and identified the predictors of major adverse events
      using multivariable analysis. RESULTS: In-hospital mortality rate was 0.7%
      (1/134). During follow-up, 46 patients had major adverse events. The 1-, 3-, and
      5-year rates of freedom from major adverse events were 79.8%, 71.4%, and 63.6%,
      respectively. The independent risk factors for major adverse events were initial
      aortic diameter >=40 mm (hazard ratio 3.735, 95% confidence interval 1.888-7.390;
      P < 0.001) and false-lumen diameter > true-lumen diameter (hazard ratio 3.411,
      95% confidence interval 1.491-7.806; P = 0.004). CONCLUSIONS: Initial aortic
      diameter >=40 mm and false-lumen diameter > true-lumen diameter are predictors of
      major adverse events after uncomplicated ATBAD. Patients with these risk factors
      may benefit from early endovascular intervention. Clinical registration number:
      UMIN 000025388, https://upload.umin.ac.jp/cgi-open
      bin/ctr_e/ctr_view.cgi?recptno=R000029229.

PMID- 29049808
TI  - Cold-inducible ribonucleic acid-binding protein attenuates acute kidney injuries
      after deep hypothermic circulatory arrest in rats.
AB  - OBJECTIVES: Cold-inducible ribonucleic acid-binding protein (CIRP) has been
      identified to play a role in the antiapoptotic effect of hypothermia. We sought
      to investigate the renoprotection of CIRP in a rat model of deep hypothermic
      circulatory arrest. METHODS: Overexpression and knockdown of CIRP were achieved
      in vivo by directly injecting lentivirus vectors containing packaging lentivirus
      (pL)/internal ribosome entry site (IRES)/green fluorescent protein (GFP)-CIRP or
      pL/short hairpin RNA (shRNA)/F-cold inducible RNA binding protein (F-CIRP)-A into
      the renal parenchyma of rats 7 days before deep hypothermic circulatory arrest
      under the ultrasound guidance. The vehicles or control lentivirus vectors were
      given to the control group or the control vector group, respectively. Renal
      function and apoptosis activity were evaluated by serum cystatin C, serum/tissue
      neutrophil gelatinase-associated lipocalin and terminal deoxynucleotidyl
      transferase 2'-deoxyuridine, 5'-triphosphate nick-end labelling assay at 24 h
      after surgery. The expression of CIRP messenger RNA (mRNA) was assessed by
      quantitative real-time polymerase chain reaction. Protein expression of CIRP and
      caspase 3 was tested by Western blot. RESULTS: Compared with the sham group, rats
      in the control group showed increased expression of CIRP mRNA, CIRP protein,
      caspase 3 and the apoptotic rate (P < 0.01). However, when compared with the
      control group, rats in the pL/IRES/GFP-CIRP group showed significantly decreased
      caspase 3 and apoptosis activities while further increased expression of CIRP
      mRNA and protein. Rats in the pL/shRNA/F-CIRP-A group showed increased caspase 3
      and apoptosis activities and further decreased expression of CIRP mRNA and
      protein (P < 0.01), when compared with the control group. Renal function was
      markedly protected in the pL/IRES/GFP-CIRP group and impaired in the pL/shRNA/F
      CIRP-A group. CONCLUSIONS: Our findings suggest that the CIRP exerts a robust
      renoprotective effect by inhibiting apoptosis in the rat model of deep
      hypothermic circulatory arrest.

PMID- 29049809
TI  - Association of Quality Improvement Registry Participation With Appropriate Follow
      up After Vascular Procedures.

PMID- 29049810
TI  - The use of ultrasound in the management of a life-threatening malignant
      laryngotracheal obstruction.
AB  - Ultrasound is becoming a valuable diagnostic tool in the armamentarium of
      thoracic surgeons. We report its use to follow stent placement in the
      laryngotracheal position for management of life-threatening neoplastic
      obstruction. For this purpose, a 15-MHz linear probe was placed in the midline at
      the level of the cricoid cartilage. Ultrasound performed daily at bedside showed
      normal movement of vocal folds and no stent dislocation. This strategy may be an
      alternative to computed tomography scan or endoscopy to follow stent placement in
      extrathoracic airways.

PMID- 29049811
TI  - Effect of cone reconstruction on right ventricular function in patients with
      Ebstein's anomaly: a meta-analysis.
AB  - OBJECTIVES: Cone reconstruction (CR) is a novel technique for surgically treating
      the tricuspid valve and right ventricle (RV) in patients with Ebstein's anomaly.
      However, precise changes in the RV function after CR remain unclear. This study
      aimed to evaluate the RV size and New York Heart Association (NYHA) functional
      class by conducting a meta-analysis of reported data. METHODS: The MEDLINE,
      EMBASE, Cochrane Library and China National Knowledge Infrastructure databases
      were searched for relevant studies. The variables were RV measurements, NYHA
      functional classes and tricuspid valve regurgitation grades. A fixed/random
      effects model was used to summarize the estimates of mean difference with
      standard error. Sensitivity analysis was conducted to ascertain the primary
      origin of the heterogeneity. RESULTS: Nine studies that involved 210 patients
      were included. The results demonstrated that after CR, the functional RV volume
      significantly decreased, NYHA functional class improved and tricuspid valve
      regurgitation grade decreased. CONCLUSIONS: Thus, CR appeared to be a positive
      approach for Ebstein's anomaly, with good results being obtained for the RV size
      and NYHA functional class. Because some limitations could not be overcome,
      studies with more data on RV and longer follow-ups are required to confirm our
      study results.

PMID- 29049812
TI  - Mild Traumatic Brain Injury and Mental Health-Reply.

PMID- 29049813
TI  - Assessment of Pain Anxiety, Pain Catastrophizing, and Fear of Pain in Children
      and Adolescents With Chronic Pain: A Systematic Review and Meta-Analysis.
AB  - Objective: To conduct a systematic review of pain anxiety, pain catastrophizing,
      and fear of pain measures psychometrically established in youth with chronic
      pain. The review addresses three specific aims: (1) to identify measures used in
      youth with chronic pain, summarizing their content, psychometric properties, and
      use; (2) to use evidence-based assessment criteria to rate each measure according
      to the Society of Pediatric Psychology (SPP) guidelines; (3) to pool data across
      studies for meta-analysis of shared variance in psychometric performance in
      relation to the primary outcomes of pain intensity, disability, generalized
      anxiety, and depression. Methods: We searched Medline, Embase, PsycINFO, and
      relevant literature for possible studies to include. We identified measures
      studied in youth with chronic pain that assessed pain anxiety, pain
      catastrophizing, or fear of pain and extracted the item-level content. Study and
      participant characteristics, and correlation data were extracted for summary and
      meta-analysis, and measures were rated using the SPP evidence-based assessment
      criteria. Results: Fifty-four studies (84 papers) met the inclusion criteria,
      including seven relevant measures: one assessed pain anxiety, three pain
      catastrophizing, and three fear of pain. Overall, five measures were rated as
      "well established." We conducted meta-analyses on four measures with available
      data. We found significant positive correlations with the variables pain
      intensity, disability, generalized anxiety, and depression. Conclusion: Seven
      measures are available to assess pain anxiety, pain catastrophizing, and fear of
      pain in young people with chronic pain, and most are well established. We present
      implications for practice and directions for future research.

PMID- 29049815
TI  - Potential Health Implications Related to Fracking.

PMID- 29049814
TI  - Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in
      Residents Born Outside the United States With and Without Medical Comorbidities
      in a Simulation Model.
AB  - Importance: Testing for and treating latent tuberculosis infection (LTBI) is
      among the main strategies to achieve TB elimination in the United States. The
      best approach to testing among non-US born residents, particularly those with
      comorbid conditions, is uncertain. Objective: To estimate health outcomes, costs,
      and cost-effectiveness of LTBI testing and treatment among non-US born residents
      with and without medical comorbidities. Design, Setting, and Participants:
      Decision analytic tree and Markov cohort simulation model among non-US born
      residents with no comorbidities, with diabetes, with HIV infection, or with end
      stage renal disease (ESRD) using a health care sector perspective with 3% annual
      discounting. Strategies compared included no testing, tuberculin skin test (TST),
      interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only
      for TST-positive results; both tests positive indicates LTBI), and confirm
      negative (initial IGRA, then TST for IGRA-negative; any test positive indicates
      LTBI). All strategies were coupled to treatment with 3 months of self
      administered rifapentine and isoniazid. Main Outcomes and Measures: Number needed
      to test and treat to prevent 1 case of TB reactivation, discounted quality
      adjusted life-years (QALYs), discounted lifetime medical costs, and incremental
      cost-effectiveness ratios (ICERs). Results: Improving health outcomes increased
      costs, with choice of test dependent on willingness to pay. Strategies ranked by
      ascending costs and benefits: no testing, confirm positive, TST, IGRA, and
      confirm negative. The ICERs varied by non-US born patient risk group: patients
      with no comorbidities, IGRA was likely cost-effective at $83 000/QALY; patients
      with diabetes, both confirm positive ($53 000/QALY) and IGRA ($120 000/QALY) were
      likely cost-effective; patients with HIV, confirm negative was clearly preferred
      ($63 000/QALY); and patients with ESRD, no testing was cost-effective. Increased
      LTBI prevalence and reduced return for TST reading improved IGRA's relative
      performance. In 10 000 probabilistic simulations among non-US born patients with
      no comorbidities, with diabetes, and with HIV, some form of testing was virtually
      always cost-effective. These simulations highlight the uncertainty of test choice
      for non-US born patients with no comorbidities and non-US born patients with
      diabetes, but strategies including IGRA were preferred in over 60% of simulations
      for all non-US born populations except those with ESRD. Conclusions and
      Relevance: Testing for and treating LTBI among non-US born residents with and
      without selected comorbidities is likely cost-effective except among those with
      ESRD in whom competing risks of death limit benefits. Strategies including IGRA
      fell below a $100 000/QALY willingness-to-pay threshold for non-US born patients
      with no comorbidities, patients with diabetes, and patients with HIV.

PMID- 29049816
TI  - Triple ultrasonography for iatrogenic acute aortic dissection caused by axillary
      arterial perfusion.
AB  - Iatrogenic aortic dissection caused by axillary arterial cannulation or perfusion
      becomes a fatal complication of cardiopulmonary bypass when surgeons do not
      recognize it in the surgical field of view immediately during surgery. Therefore,
      we routinely monitor the aorta using 'triple ultrasonography' during
      cardiovascular surgery. An 85-year-old woman underwent partial arch replacement
      for chronic type A aortic dissection. During cardiopulmonary bypass, acute aortic
      dissection was observed in the aortic arch from the right axillary artery on real
      time transoesophageal echocardiography. Epiaortic and neck surface
      ultrasonography detected malperfusion of the carotid artery. During femoral
      arterial perfusion, the patient was rescued with partial aortic replacement.
      Axillary artery cannulation is useful for cardiopulmonary bypass but confers a
      risk of iatrogenic aortic dissection that cannot be confirmed by surgeons
      surgically. The transoesophageal echocardiography can guard the aorta while
      systemic perfusion is initiated. Furthermore, epiaortic and neck surface
      echography can be incorporated to transoesophageal echocardiography. Triple
      ultrasonography allows for the detection of iatrogenic aortic dissection.

PMID- 29049817
TI  - Long-term patency of on- and off-pump coronary artery bypass grafting with
      bilateral internal thoracic arteries: the significance of late string sign
      development in the off-pump technique.
AB  - OBJECTIVES: This study aimed to examine the effect of off-pump coronary artery
      bypass grafting (CABG) in patients who underwent revascularization with bilateral
      internal thoracic arteries (ITAs). METHODS: Between January 2000 and December
      2014, 499 patients underwent isolated CABG with bilateral ITAs for complete
      revascularization of the left coronary system at our institution. On-pump CABG
      was performed in 137 patients, and off-pump CABG was performed in 362 patients.
      We retrospectively compared the clinical outcomes and patency of the ITAs.
      RESULTS: The off-pump group showed less respiratory failure and required a
      shorter postoperative stay than the on-pump group. The survival probability,
      freedom from cardiac events and early graft patency were similar in both groups.
      Five-year patency of the ITA anastomosed to the left anterior descending artery
      was significantly greater in the on-pump group than in the off-pump group (98.8%
      vs 91.2%, P = 0.010). The incidence of string change in the off-pump group was
      higher than that in the on-pump group (P = 0.017). There was no significant
      difference between the groups in the 5-year patency of the ITA anastomosed to the
      left circumflex artery (on-pump group: 93.8%, off-pump group: 91.8%; P = 0.46).
      CONCLUSIONS: The early graft patency and the late patency of the ITA anastomosed
      to the left circumflex artery between the groups were similar, implying an
      equivalent quality of anastomoses. However, the patency of the ITA anastomosed to
      the left anterior descending artery in the off-pump group showed late
      deterioration, mainly because of string sign development.

PMID- 29049818
TI  - Dor procedure for pulmonary atresia with intact ventricular septum in an infant.
AB  - Pulmonary atresia with intact ventricular septum and right ventricle-dependent
      coronary circulation confers a high risk for myocardial infarction and
      complications of ischaemia, including left ventricle aneurysms. We describe an
      infant with pulmonary atresia with intact ventricular septum and right ventricle
      dependent coronary circulation and a left ventricle apical aneurysm who
      successfully underwent the Dor procedure and a subsequent Fontan operation.
      Surgery for postinfarction left ventricle aneurysm can be considered in infants.

PMID- 29049819
TI  - Treatment of a degenerated sutureless Sorin Perceval(r) valve using an Edwards
      SAPIEN 3.
AB  - Valve-in-valve implantation is an alternative to reoperation for patients with
      degenerated bioprostheses. This case report presents a 75-year-old woman
      presenting with worsening dyspnoea according New York Heart Association (NYHA)
      Class III after she had received a Sorin Perceval(r) S sutureless valve due to
      severe aortic valve stenosis 5 years ago. Echocardiography revealed a degenerated
      Perceval valve with severe valvular aortic regurgitation and stenosis. After
      exclusion of acute infective endocarditis, an Edwards SAPIEN 3 was implanted
      leading to an immediate haemodynamic improvement. A cerebral protection device
      caught a big embolized piece of material in the left carotid artery filter. The
      case demonstrates that not only suture-based stented and stentless bioprostheses
      can be treated by a valve-in-valve strategy, but it is also feasible to treat a
      failed sutureless Sorin Perceval using a balloon-expandable SAPIEN 3.

PMID- 29049821
TI  - Mainstreaming Latent Tuberculosis Infection Testing and Treatment in the United
      States: Who and How.

PMID- 29049822
TI  - Treatment of Acute Upper Airway Obstruction.

PMID- 29049820
TI  - Association of History of Gestational Diabetes With Long-term Cardiovascular
      Disease Risk in a Large Prospective Cohort of US Women.
AB  - Importance: Previous studies identify gestational diabetes (GD) as a risk factor
      for intermediate markers of cardiovascular disease (CVD) risk; however, few are
      prospective, evaluate hard CVD end points, or account for shared risk factors
      including body weight and lifestyle. Objective: To prospectively evaluate history
      of GD in relation to incident CVD risk. Design, Setting, and Participants: The
      Nurses' Health Study II (NHS II) is an observational cohort study of US female
      nurses established in 1989, with ongoing follow-up. Biennial questionnaires
      updated behavioral characteristics, health outcomes, and lifestyle factors.
      Multivariable Cox models estimated the hazard ratio (HR) and 95% CI for CVD risk.
      We included 89 479 women who reported at least 1 pregnancy and were free of CVD
      and cancer at baseline. Follow-up through May 31, 2015, was complete for more
      than 90% of eligible participants. Exposures: History of GD was self-reported at
      baseline (1989) via questionnaire and updated every 2 years. Main Outcomes and
      Measures: We observed 1161 incident self-reported nonfatal or fatal myocardial
      infarction or stroke, confirmed via medical records. Results: Participants had a
      mean (SD) age of 34.9 (4.7) years. Adjusting for age, prepregnancy body mass
      index, and other covariates, GD vs no GD was associated with subsequent CVD (HR,
      1.43; 95% CI, 1.12-1.81). Additional adjustment for weight gain since pregnancy
      and updated lifestyle factors attenuated the association (HR, 1.29; 95% CI, 1.01
      1.65). Classifying GD by progression to T2D in relation to CVD risk indicated a
      positive association for GD with progression to T2D vs no GD or T2D (HR, 4.02;
      95% CI, 1.94-8.31), and an attenuated relationship for GD only (HR, 1.30; 95% CI,
      0.99-1.71). Conclusions and Relevance: Gestational diabetes was positively
      associated with CVD later in life, although the absolute rate of CVD in this
      younger cohort of predominantly white women was low. This relationship is
      possibly mediated in part by subsequent weight gain and lack of healthy
      lifestyle.

PMID- 29049823
TI  - Lipoprotein Apheresis for Sitosterolemia.

PMID- 29049824
TI  - Unraveling the Epidemiology of Oral Human Papillomavirus Infection.

PMID- 29049825
TI  - Comparison of Clinical Characteristics and Outcomes of Peripartum Cardiomyopathy
      Between African American and Non-African American Women.
AB  - Importance: Peripartum cardiomyopathy (PPCM) disproportionately affects women of
      African ancestry, but well-powered studies to explore differences in severity of
      disease and clinical outcomes are lacking. Objective: To compare the clinical
      characteristics, presentation, and outcomes of PPCM between African American and
      non-African American women. Design, Setting, and Participants: This retrospective
      cohort study using data from January 1, 1986, through December 31, 2016,
      performed at the University of Pennsylvania Health System, a tertiary referral
      center serving a population with a high proportion of African American
      individuals, included 220 women with PPCM. Main Outcomes and Measures:
      Demographic and clinical characteristics and echocardiographic findings at
      presentation, as well as clinical outcomes including cardiac recovery, time to
      recovery, cardiac transplant, persistent dysfunction, and death, were compared
      between African American and non-African American women with PPCM. Results: A
      total of 220 women were studied (mean [SD] age at diagnosis, 29.5 [6.6] years).
      African American women were diagnosed with PPCM at a younger age (27.6 vs 31.7
      years, P < .001), were diagnosed with PPCM later in the postpartum period, and
      were more likely to present with a left ventricular ejection fraction less than
      30% compared with non-African American women (48 [56.5%] vs 30 [39.5%], P = .03).
      African American women were also more likely to worsen after initial diagnosis
      (30 [35.3%] vs 14 [18.4%], P = .02), were twice as likely to fail to recover (52
      [43.0%] vs 24 [24.2%], P = .004), and, when they did recover, recovery took at
      least twice as long (median, 265 vs 125.5 days; P = .02) despite apparent
      adequate treatment. Conclusions and Relevance: In a large cohort of women with
      well-phenotyped PPCM, this study demonstrates a different profile of disease in
      African American vs non-African American women. Further work is needed to
      understand to what extent these differences stem from genetic or socioeconomic
      differences and how treatment of African American patients might be tailored to
      improve health outcomes.

PMID- 29049826
TI  - Bilateral uniportal video-assisted thoracoscopic lung resections.
AB  - The introduction of uniportal video-assisted thoracoscopic surgery into the field
      of minimally invasive thoracic surgery has its revolutionary effect by bringing
      the surgical trauma to the minimum. As a result, less postoperative pain and
      complications may be achieved through this technology. This may convince us as
      thoracic surgeons to become more liberal and to extend the indications of
      performing 'single-staged' bilateral video-assisted thoracoscopic surgery.
      Herein, we described our technique in bilateral pulmonary resections. A 32-year
      old woman was admitted to our department with 3 small bilateral lesions. Two
      wedge resections were performed on the left side, followed by S6 segmentectomy on
      the right side.

PMID- 29049827
TI  - Cost-effectiveness of PCSK9 Inhibitors: Proof in the Modeling.

PMID- 29049830
TI  - Acute DeBakey Type I aortic dissection without intimal tear in the arch: is total
      arch replacement the right choice?
AB  - OBJECTIVES: Surgical management of acute DeBakey Type I aortic dissection without
      intimal tear in the aortic arch is controversial. This study compared short- and
      long-term outcomes of total arch replacement (TAR) versus limited ascending
      aorta/hemiarch replacement (no-TAR) in a consecutive series of patients. METHODS:
      Between January 1998 and December 2015, 220 consecutive patients were operated
      for DeBakey Type I acute aortic dissection; 135 cases did not exhibit an intimal
      entry tear in the aortic arch and were subsequently selected to comprise the
      primary study cohort. A secondary subgroup analysis was made within these 135
      cases, which comprised patients who received antegrade cerebral perfusion as the
      neuroprotective strategy of choice (n = 45). RESULTS: Mean follow-up period was 5
      +/- 4 years. Among the patients selected, 21 (16%) underwent TAR. Thirty-day
      mortality was higher in the TAR group (38% vs 21%, P = 0.04). Postoperative
      complication rates were similar between the groups (61% vs 73%, P = 0.31). Long
      term mortality and late aortic reintervention rates were also similar (7% vs 30%,
      P = 0.36 and 27% vs 14%, P = 0.32, respectively). From the subgroup of patients
      with antegrade cerebral perfusion, 14 (31%) underwent TAR and 31 (69%) had no
      TAR. Mean follow-up-time was 3 +/- 2 years. Thirty-day mortality was higher in
      the TAR group (50% vs 16%, P < 0.01), postoperative complications, long-term
      mortality and late aortic reintervention rates were similar (64% vs 69%, P =
      0.73; 0% vs 19%, P = 0.22; 29% vs 8%, P = 0.17, respectively). CONCLUSIONS: TAR
      was associated with higher 30-day mortality compared with the less extensive
      hemiarch replacement. In the long term, TAR showed a trend of improved survival
      and higher reintervention rate.

PMID- 29049832
TI  - Requiem for a Scaffold.

PMID- 29049831
TI  - Improving myocardial fractional flow reserve in coronary atherosclerosis via CX37
      gene silence: a preclinical validation study in pigs.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of CX37 gene
      silence on myocardial fractional flow reserve (FFR). METHODS: A total of 90 male
      pigs were randomly divided into saline, mock and 3 different doses (5, 10 and 20
      ul) of CX37 viral suspension groups that could induce coronary plaque formation
      with high-fat diet. After performing myocardial FFR by intravascular ultrasound,
      different doses of CX37 viral suspension, saline and mock small interfering RNA
      (siRNA) were transfected into the related coronary. The FFR, the myocardial
      enzymes and the cardiac structures and functions of the pigs were detected at
      baseline, 4th, 8th and 12th week after transfection, respectively. RESULTS:
      Repeated measures analysis of variance comparison showed that the difference in
      the FFR among the 5 groups was statistically significant (F = 27.0, P < 0.01).
      Post hoc analysis showed that FFR were highest in the siRNA CX37 group (20 ul),
      followed by the siRNA CX37 group (10 ul) and the siRNA CX37 group (5 ul), and
      lowest in the mock and saline groups. Left ventricular end-diastolic diameter was
      significantly smaller and ejection fraction was obviously higher in the 3 siRNA
      CX37 groups compared with the untreated groups. CONCLUSIONS: Our study showed
      that FFR levels increased along with decreased doses of siRNA CX37 lentivirus,
      indicating that siRNA CX37 lentivirus may reduce the risk of coronary
      atherosclerosis and provide a potential approach to treat coronary heart disease.

PMID- 29049833
TI  - Intramurally spreading aortic intimal sarcoma masquerading as ruptured aortic
      dissection.
AB  - Preoperative diagnosis of aortic sarcomas is often difficult. Herein, we describe
      a case of a 68-year-old man who had an aortic intimal sarcoma with aortic wall
      hypertrophy that masqueraded as a thrombosed aortic dissection or mural thrombus
      on computed tomography. Because of the sudden appearance and rapid growth of the
      tumour surrounding the left subclavian artery with precordial pain and
      haemosputum, left subclavian arterial rupture caused by aortic dissection was
      suspected, requiring emergent total arch replacement. Surgery revealed an intimal
      sarcoma, not an aortic dissection, with the thickening of the fragile intima
      spreading into the aorta. Thus, an intramurally spreading aortic intimal sarcoma
      should be suspected when computed tomography reveals an irregular thickening of
      the aortic intima.

PMID- 29049834
TI  - Percutaneous left atrial unloading to prevent pulmonary oedema and to facilitate
      ventricular recovery under extracorporeal membrane oxygenation therapy.
AB  - OBJECTIVES: Left-sided unloading during extracorporeal membrane oxygenation
      (ECMO) therapy is crucial to prevent pulmonary oedema and facilitate ventricular
      recovery. We present the case of a 55-year-old man under ECMO therapy with pre
      existing left ventricular (LV) thrombus formation and in need of ventricular
      unloading. METHODS: We implanted a 21-Fr TandemHeart Protek Solo trans-septal
      cannula into the left atrium using a trans-septal approach via the femoral vein.
      The cannula was connected to the venous line of the ECMO circuit. A flow probe
      and a clamp to reduce flow, if necessary, were attached to the left atrium line.
      Left atrium flow was adjusted to 900 ml/min under transoesophageal
      echocardiography control to keep the atrial septum in the mid-line and to prevent
      suction of the inflow cannula. RESULTS: After 9 days, the patient was weaned step
      wise from ECMO and the TandemHeart cannula, which was then explanted. The patient
      is in New York health Association Class II without neurological sequelae
      (Cerebral Performance Scale 1). After 3 months, the patient has fully recovered
      and is working daily. The LV function is still moderately impaired, and the size
      of the LV thrombus remains the same. The atrial septum shows no residual defect.
      CONCLUSIONS: Percutaneous trans-septal insertion of a TandemHeart cannula
      incorporated in an ECMO circuit for the prevention of pulmonary oedema and
      subsequent weaning from extracorporeal circulation was feasible and safe in a
      patient with cardiogenic shock and an LV thrombus.

PMID- 29049835
TI  - The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell
      Function in Patients With Leber's Hereditary Optic Neuropathy.
AB  - Purpose: The photopic negative response (PhNR) is a slow negative component of a
      flash photopic full-field ERG that has been shown to be specific for retinal
      ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in
      patients with Leber's hereditary optic neuropathy (LHON) in which the loss of
      central acuity can make it difficult to monitor patients with standard metrics.
      The purpose of this study was to evaluate the use of PhNR as an objective
      noninvasive clinical metric in LHON. Methods: Full-field photopic ERG recordings
      were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on
      blue stimulus. The PhNR was identified using a computer-based automated detection
      system, and data were manually examined to remove movement artifacts. Results:
      The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and
      affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P <
      0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude
      between carriers and controls (P < 0.05) and between carriers and affected (P <
      0.01). Conclusions: We are able to demonstrate that the PhNR amplitude is
      significantly decreased in patients affected by LHON compared to carriers in a
      well-described pedigree. Surprisingly, there was also a decrease in PhNR in
      carriers, suggesting potential subclinical RGC dysfunction in some carriers. This
      is important in patients affected with LHON who typically have a dense central
      scotoma. The PhNR may be a useful objective outcome measure for future clinical
      trials.

PMID- 29049836
TI  - Fluid accumulation after closure of atrial septal defects: the role of colloid
      osmotic pressure.
AB  - OBJECTIVES: Following paediatric cardiac surgery with cardiopulmonary bypass
      (CPB), there is a tendency for fluid accumulation. The colloid osmotic pressure
      of plasma (COPp) and interstitial fluid (COPi) are determinants of transcapillary
      fluid exchange but only COPp has been measured in sick children. The aim of this
      study was to assess the net colloid osmotic pressure gradient in children
      undergoing atrial septal defect closure. METHODS: Twenty-three patients had
      interventional and 18 had surgical atrial septal defect closures. Interstitial
      fluid was harvested using a wick method before and after surgery with CPB with
      concomitant blood samples. COP was measured using a colloid osmometer for small
      fluid samples. Baseline COP was compared with data from healthy children.
      RESULTS: COPp at baseline was 21.9 +/- 2.8 and 21.4 +/- 2.2 mmHg in the
      interventional and surgical groups, respectively, and was significantly lower
      than in healthy children (25.5 +/- 3.1 mmHg) (P < 0.001). In the surgical group,
      the use of CPB significantly reduced COPp to 16.9 +/- 2.9 mmHg (P < 0.001) and
      the colloid osmotic gradient [DeltaCOP (COPp - COPi)] to 2.9 +/- 3.8 mmHg (P <
      0.001) compared with interventional procedure. One hour after the procedure, COPi
      was 15.6 +/- 3.8 mmHg and 9.9 +/- 2.1 mmHg (P < 0.001) and the DeltaCOP was 5.4
      +/- 3.0 mmHg and 9.1 +/- 3.1 mmHg (P < 0.003) in the interventional and surgical
      groups, respectively. CONCLUSIONS: Baseline COPp and COPi were lower in atrial
      septal defect patients compared with healthy children. The significantly lower
      COP gradient during CPB may explain the tendency for more fluid accumulation with
      pericardial effusion in the surgical group. The increased COP gradient after CPB
      may represent an oedema-preventive mechanism.

PMID- 29049837
TI  - Clinical application of projection mapping technology for surgical resection of
      lung metastasis.
AB  - Indocyanine green fluorescent image-guided surgery was developed to identify
      primary and metastatic nodules of various malignancies. However, currently,
      surgeons need to identify the fluorescent image on a monitor, which impedes
      surgical procedures. Herein, we developed a novel projection mapping device that
      can cast the real-time fluorescent image onto the surface of the targeted organ.
      We performed surgical resection of a lung metastasis of hepatoblastoma using this
      technique. The projection mapping technique clearly detected the pulmonary
      lesion, and no other lesions were identified in the ipsilateral thorax. The
      patient is well and free of recurrence 2 years after surgery.

PMID- 29049838
TI  - Predicting long-term survival after coronary artery bypass graft surgery.
AB  - OBJECTIVES: To develop a model for predicting long-term survival following
      coronary artery bypass graft surgery. METHODS: This study included 46 573
      patients from the Australian and New Zealand Society of Cardiac and Thoracic
      Surgeons (ANZCTS) registry, who underwent isolated coronary artery bypass graft
      surgery between 2001 and 2014. Data were randomly split into development (23 282)
      and validation (23 291) samples. Cox regression models were fitted separately,
      using the important preoperative variables, for 4 'time intervals' (31-90 days,
      91-365 days, 1-3 years and >3 years), with optimal predictors selected using the
      bootstrap bagging technique. Model performance was assessed both in validation
      data and in combined data (development and validation samples). Coefficients of
      all 4 final models were estimated on the combined data adjusting for hospital
      level clustering. RESULTS: The Kaplan-Meier mortality rates estimated in the
      sample were 1.7% at 90 days, 2.8% at 1 year, 4.4% at 2 years and 6.1% at 3 years.
      Age, peripheral vascular disease, respiratory disease, reduced ejection fraction,
      renal dysfunction, arrhythmia, diabetes, hypercholesterolaemia, cerebrovascular
      disease, hypertension, congestive heart failure, steroid use and smoking were
      included in all 4 models. However, their magnitude of effect varied across the
      time intervals. Harrell's C-statistics was 0.83, 0.78, 0.75 and 0.74 for 31-90
      days, 91-365 days, 1-3 years and >3 years models, respectively. Models showed
      excellent discrimination and calibration in validation data. CONCLUSIONS: Models
      were developed for predicting long-term survival at 4 time intervals after
      isolated coronary artery bypass graft surgery. These models can be used in
      conjunction with the existing 30-day mortality prediction model.

PMID- 29049839
TI  - Pusher preventing maximum expansion of transfemoral transcatheter valves.
AB  - To report on 2 rare cases of balloon-expandable transfemoral transcatheter aortic
      valve implantation, where a trapped balloon led to complications requiring acute
      intervention. Both patients were elderly with increased risk profile and had been
      discussed by the heart team. After standard positioning of the valves using a
      transfemoral approach, retrieval of the pusher before deployment of the valve was
      missed. In 1 patient, rapid pacing was continued, the balloon deflated, the
      pusher pulled back and the balloon repositioned and reinflated. In the other
      patient, valve migration into the left ventricle occurred. A second valve was
      deployed. The embolized valve was then recovered from the ventricle via
      transapical access. Complications can occur in transcatheter aortic valve
      implantation, even when they are very rare. A predeployment check list,
      indicating key procedural steps on a standardized basis, should always be
      followed to easily prevent mishaps.

PMID- 29049840
TI  - Evaluating interest in narrative therapy for decision making about pectus
      excavatum treatment.
AB  - OBJECTIVES: The decision to proceed with surgical treatment for pectus excavatum
      (PE) is rarely clear-cut. Patients interested in treatment are referred for
      evaluation by numerous different specialists, but psychosocial counselling is
      currently not included in this process. Our objective was to assess whether PE
      patients would be interested in formal assistance with the decision-making
      process surrounding PE surgery using narrative therapy principles. METHODS:
      Ninety-seven untreated PE patients at 5 different institutions in 4 countries
      completed a questionnaire consisting of 13 questions, with 3 questions
      specifically evaluating interest in narrative therapy. RESULTS: Eighty-two
      percent of participants were interested in narrative therapy to assist with the
      decision-making process surrounding PE surgery. Individuals most interested in
      narrative therapy tend to be more interested in correction (P < 0.05) to improve
      the way they feel about their body (P < 0.05). CONCLUSIONS: The majority of PE
      patients are interested in narrative therapy to aid the decision-making process
      about treatment. We propose that narrative therapy should be offered to PE
      patients during the treatment evaluation process to address the psychosocial
      difficulties associated with PE and the surgical decision-making process overall.
      Future studies should assess the effectiveness of this interdisciplinary model.

PMID- 29049841
TI  - Predictive value of the 8th edition American Joint Commission Cancer (AJCC) nodal
      staging system for patients with cutaneous squamous cell carcinoma of the head
      and neck.
AB  - BACKGROUND: The 8th edition American Joint Committee on Cancer (AJCC8) provides
      the same nodal staging system for mucosal and cutaneous squamous cell carcinoma
      of the head and neck (HNcSCC) and includes extranodal extension (ENE) as an
      adverse prognostic criterion. This study evaluates the prognostic efficacy of the
      AJCC8 pathologic nodal staging system (pN) for HNcSCC. METHODS: Univariate
      analysis of 382 patients with metastatic HNcSCC staged according to both the 7th
      (AJCC7) and the 8th edition staging systems. RESULTS: The AJCC7 pN3 category was
      associated with reduced disease specific survival (DSS HR 5.49; 95% CI: 1.83
      16.53; P = 0.002) and overall survival (OS HR 3.42; 95% CI: 1.54-7.58; P = 0.002)
      as compared with pN1. However, no difference was observed between pN1, pN2, and
      pN3 categories as defined by the AJCC8. Also, when comparing Stages III and IV as
      defined by AJCC8, there was no difference in DSS (HR 0.75; 95% CI: 0.34-1.67; P =
      0.478) or OS (HR 0.88; 95% CI: 0.51-1.51; P = 0.648). CONCLUSION: The AJCC8
      performed poorly as a prognostic indicator for patients with metastatic HNcSCC in
      this cohort. HNcSCC would benefit from a staging system that accounts for its
      unique biologic characteristics distinct from mucosal SCC.

PMID- 29049842
TI  - Acid digestion on river influenced shelf sediment organic matter: Carbon and
      nitrogen contents and isotopic ratios.
AB  - RATIONALE: Natural stable isotope ratios (delta13 Corg and delta15 N values) and
      associated elemental concentrations (i.e. total organic carbon and total nitrogen
      contents) preserved in marine sediments are frequently used for the determination
      of paleo-environmental processes such as the origin of organic matter. Previous
      studies highlighted biases in the determination of such geochemical proxies due
      to pre-analysis acid treatment methods. This study is the first systematic
      comparison of the effect of acid treatment methods on bulk organic matter using a
      unique sedimentary system, under two contrasting climatic contexts (i.e. glacial
      vs interglacial). METHODS: We used the most common method for pre-treatment
      analysis, which consists of the acidification of bulk sediments followed by
      several rinses with deionised water. We investigated the effect of acid type
      (hydrochloric and acetic acid), and also acid strength (from 0.2 to 10 mol.L-1 )
      on the delta13 Corg , delta15 N, TOC, TN and C/N values of three samples from the
      Gulf of Lion. Two of them (S.304 and S.102) were deposited during glacial maxima
      (i.e. high sedimentation rate, low porosity and high terrestrial inputs) whereas
      S.157 characterizes interglacial conditions (high porosity, high foraminifera
      content, low sedimentation rates and low terrestrial inputs). RESULTS: For all
      three samples the delta13 Corg values are between -21.7 and -24.40/00 with the
      TOC varying from 0.56 to 0.84 %wt/wt. The delta15 N values are more stable with
      an average value of 3.0 +/- 0.10/00 with a TN average of 0.08 +/- 0.002 %wt/wt.
      CONCLUSIONS: We show that acid type did not significantly affect results. We also
      find that (i) glacial and interglacial samples do not react similarly to acid pre
      treatment, (ii) high acid strength (>1.5 mol.L-1 ) induces significant bias on
      delta13 Corg and TOC values, and therefore on C/N ratios; (iii) 25% of an
      isotopically distinct pool of organic carbon was lost when using acid
      concentrations of 0.2-1.5 mol.L-1 , affecting delta13 Corg values by more than
      1.50/00; and (iv) geochemical evidence indicates that the leachable organic
      carbon pool is preferentially composed of terrestrial organic matter. These
      findings call for precautions when using C/N ratios and associated delta13 Corg
      values for paleo-environmental and climate reconstructions.

PMID- 29049845
TI  - Impact of the initial fitness level on the effects of a structured exercise
      therapy during pediatric stem cell transplantation.
AB  - BACKGROUND: Before and after hematopoietic stem cell transplantation (HSCT), most
      patients suffer from psychophysical limitations due to the treatment. Exercise
      interventions demonstrate beneficial effects on, for example, strength,
      endurance, or health-related quality of life during and after HSCT, but with a
      great variation among patients concerning the response to exercise. This study
      examines the influence of the initial fitness on the effects of an exercise
      therapy in pediatric HSCT. PROCEDURE: Fifty-three children and adolescents (10.9
      +/- 3.5 years) scheduled for HSCT were randomized into an exercise intervention
      group (IG) or a control group (CG). During hospitalization, the IG performed
      endurance, strength, and flexibility training three times per week. The CG
      included a nonexercise program. A 6-min walk test was completed before and after
      the inpatient period. Baseline results (6-min walking distance [6MWD]) were used
      to split both groups into the following: IGUNFIT , n = 14; IGFIT , n = 12;
      CGUNFIT , n = 16; CGFIT , n = 11. Differences in outcome changes between groups
      were analyzed with H-test. RESULT: Intergroup comparison revealed significant
      differences between IGUNFIT and CGUNFIT (P < 0.05). The IGUNFIT increased their
      6MWD by +8% (vs. IGFIT , +1%); both CGs presented a decline in 6MWD (CGUNFIT , 
      14%; CGFIT , -16%). At discharge, the IGFIT achieved 85.5 +/- 10.3% of healthy
      reference values. CONCLUSIONS: The current results indicate that exercise during
      pediatric HSCT is feasible and contributes to prevention of treatment-related
      loss of physical function. As seen in healthy persons, patients' benefits might
      depend on their initial fitness level. As a diminished physical capability may
      result in higher training effects, impaired especially patients should engage in
      exercise.

PMID- 29049846
TI  - Successful management of transfusion-dependent congenital dyserythropoietic
      anemia type 1b with interferon alfa-2a.
AB  - The congenital dyserythropoietic anemias (CDAs) are a group of rare inherited
      blood disorders characterized by ineffective erythropoiesis as the principal
      cause of anemia. We present a child with CDA 1b-the rarest and least well
      described type-due to a mutation in the C15orf41 gene. The patient presented with
      severe in utero and neonatal manifestations, typical peripheral limb anomalies as
      well as rarely reported cardiac manifestations, visual impairment, short stature,
      and hip dysplasia. Anemia was complicated by iron overload and pronounced extra
      medullary erythropoiesis leading to skull deformities. The patient responded to
      treatment with pegylated interferon alfa-2a.

PMID- 29049844
TI  - Flavonoids inhibit chronically exposed arsenic-induced proliferation and
      malignant transformation of HaCaT cells.
AB  - BACKGROUND: Apart from exposure to UV-radiation, studies show relationship
      between skin cancer and chronic ingestion of arsenic through drinking water.
      Chemopreventive strategies could help in reducing the toxic effects of arsenic
      and arsenic-induced skin cancer. METHODS: Cytotoxicity of arsenic on human skin
      keratinocytes HaCaT cells was evaluated using MTT and trypan blue assays. Arsenic
      induced malignant transformant HaCaT cells were selected through soft agar colony
      assay. Cell cycle progression was analyzed through FACS. The expressions of genes
      modulated by arsenic were studied through RT-PCR. RESULTS: The lower
      concentrations (0.1-0.5 MUmol/L) of arsenic were non-toxic and transformed HaCaT
      cells on chronic exposure, and also enhanced the cell proliferation. Silibinin
      and fisetin reduced the arsenic-induced cell proliferation and malignant
      transformation. A slight increase in G2-M phase cell population was also
      observed. The anti-proliferation effects of flavonoids on HaCaT transformants
      were further enhanced when combined with gamma radiation. Chronic and acute
      exposure to arsenic modulated the expression of transformation-associated genes
      including Bcl-2A1, IGFL-1, Rab31, and TNC in HaCaT cells. CONCLUSIONS: Chronic
      exposure to lower arsenic concentrations caused malignant transformation of skin
      keratinocytes and that effect was attenuated by flavonoids silibinin and fisetin.
      Thus, chemoprevention could reduce arsenic-caused detrimental effects on skin
      cells.

PMID- 29049847
TI  - Neurofibromatosis type 1 and optic pathway glioma: Molecular interplay and
      therapeutic insights.
AB  - Children with neurofibromatosis type 1 (NF1) are predisposed to develop central
      nervous system neoplasms, the most common of which are low-grade gliomas (LGGs).
      The absence of human NF1 associated LGG-derived cell lines, coupled with an
      inability to generate patient-derived xenograft models, represents barriers to
      profile molecularly targeted therapies for these tumors. Thus, genetically
      engineered mouse models have been identified to evaluate the interplay between
      Nf1-deficient tumor cells and nonneoplastic stromal cells to evaluate potential
      therapies for these neoplasms. Future treatments might also consider targeting
      the nonneoplastic cells in NF1-LGGs to reduce tumor growth and neurologic
      morbidity in affected children.

PMID- 29049848
TI  - Multi-Step Crystallization of Barium Carbonate: Rapid Interconversion of
      Amorphous and Crystalline Precursors.
AB  - The direct observation of amorphous barium carbonate (ABC), which transforms into
      a previously unknown barium carbonate hydrate (herewith named gortatowskite)
      within a few hundred milliseconds of formation, is described. In situ X-ray
      scattering, cryo-, and low-dose electron microscopy were used to capture the
      transformation of nanoparticulate ABC into gortatowskite crystals, highly
      anisotropic sheets that are up to 1 MUm in width, yet only about 10 nm in
      thickness. Recrystallization of gortatowskite to witherite starts within 30
      seconds. We describe a bulk synthesis and report a first assessment of the
      composition, vibrational spectra, and structure of gortatowskite. Our findings
      indicate that transient amorphous and crystalline precursors can play a role in
      aqueous precipitation pathways that may often be overlooked owing to their
      extremely short lifetimes and small dimensions. However, such transient
      precursors may be integral to the formation of more stable phases.

PMID- 29049843
TI  - Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor
      microenvironment, and therapeutic implications.
AB  - Melanomas are metabolically heterogeneous, and they are able to adapt in order to
      utilize a variety of fuels that facilitate tumor progression and metastasis. The
      significance of metabolism in melanoma is supported by growing evidence of impact
      on the efficacy of contemporary therapies for this disease. There are also data
      to support that the metabolic phenotypes of melanoma cells depend upon
      contributions from both intrinsic oncogenic pathways and extrinsic factors in the
      tumor microenvironment. This review summarizes current understanding of the
      metabolic processes that promote cutaneous melanoma tumorigenesis and
      progression, the regulation of cancer cell metabolism by the tumor
      microenvironment, and the impact of metabolic pathways on targeted and immune
      therapies.

PMID- 29049849
TI  - Regulatory connection between the expression level of classical protein kinase C
      and pruning of climbing fibers from cerebellar Purkinje cells.
AB  - Cerebellar Purkinje cells (PCs) express two members of the classical protein
      kinase C (cPKC) subfamily, namely, PKCalpha and PKCgamma. Previous studies on
      PKCgamma knockout (KO) mice have revealed a critical role of PKCgamma in the
      pruning of climbing fibers (CFs) from PCs during development. The question
      remains as to why only PKCgamma and not PKCalpha is involved in CF synapse
      elimination from PCs. To address this question, we assessed the expression levels
      of PKCgamma and PKCalpha in wild-type (WT) and PKCgamma KO PCs using PC-specific
      quantitative real-time reverse transcription-polymerase chain reaction, western
      blotting, and immunohistochemical analysis. The results revealed that the vast
      majority of cPKCs in PCs were PKCgamma, whereas PKCalpha accounted for the
      remaining minimal fraction. The amount of PKCalpha was not up-regulated in
      PKCgamma KO PCs. Lentiviral expression of PKCalpha in PKCgamma KO PCs resulted in
      a 10-times increase in the amount of PKCalpha mRNA in the PKCgamma KO PCs,
      compared to that in WT PCs. Our quantification showed that the expression levels
      of cPKC mRNA in PKCgamma KO PCs increased roughly from 1% to 22% of that in WT
      PCs solely through PKCalpha expression. The up-regulation of PKCalpha in PKCgamma
      KO PCs significantly rescued the impaired CF synapse elimination. Although both
      PKCalpha and PKCgamma are capable of pruning supernumerary CF synapses from
      developing PCs, these results suggest that the expression levels of cPKCs in
      PKCgamma KO PCs are too low for CF pruning.

PMID- 29049851
TI  - Moments of change.

PMID- 29049850
TI  - Epigenetic control of early neurodegenerative events in diabetic retinopathy by
      the histone deacetylase SIRT6.
AB  - Diabetic retinopathy (DR) is one of the common complications associated with
      diabetes mellitus and the leading cause of blindness worldwide. Recent research
      has demonstrated that DR is not only a microvascular disease but may be a result
      of neurodegenerative processes. Moreover, glucose-induced neuron and glial cell
      damage may occur shortly after the onset of diabetes which makes the disease hard
      to diagnose at early stages. SIRT6, a NAD-dependent sirtuin deacylase, modulates
      aging, energy metabolism, and neurodegeneration. In previous studies we showed
      that SIRT6 deficiency causes major retinal transmission defects, changes in the
      expression of glycolytic genes, and elevated levels of apoptosis. Given the
      importance of glucose availability for retinal function and the critical role of
      SIRT6 in modulating glycolysis, we aimed to analyze SIRT6 participation in the
      molecular machinery that regulates the development of experimental DR. Using non
      obese diabetic mice, we determined by western blot that 2 weeks after the onset
      of the disease, high glucose concentrations induced retinal increase in a
      neovascularization promoting factor (vascular endothelial growth factor, VEGF),
      and the loss of a neuroprotective factor (brain-derived neurotrophic factor,
      BDNF) associated with reduced levels of SIRT6 and increased acetylation levels of
      its substrates (H3K9 and H3K56) suggesting a deregulation of key neural factors.
      Noteworthy, retinas from CNS conditionally deleted SIRT6 mice showed a
      resemblance to diabetic retinas exhibiting lower protein levels of BDNF factor
      and increased protein levels of VEGF. Moreover, cultured Muller glial cells
      subjected to high glucose concentrations exhibited decreased levels of SIRT6 and
      increased levels of H3K56 acetylation. In addition, the increment of VEGF levels
      induced by high glucose was reverted by the over-expression of SIRT6 in this cell
      type. Accordingly, siRNA experiments showed that, when SIRT6 was silenced, VEGF
      levels increased. Our findings suggest that epigenetically regulated
      neurodegenerative events may occur at an early diabetic stage prior to the
      characteristic proliferative and vascular changes observed at a later diabetic
      stage.

PMID- 29049852
TI  - Parental experiences of prenatal whole exome sequencing (WES) in cases of
      ultrasound diagnosed fetal structural anomaly.
AB  - OBJECTIVE: To explore parental experiences of whole exome sequencing (WES) for
      prenatal diagnosis and ascertain what influenced their decision-making to undergo
      testing. METHOD: Twelve women comprised a purposeful sample in a series of
      semistructured interviews. All had received a fetal anomaly diagnosis on
      ultrasound. A topic guide was used, and transcripts were thematically analyzed to
      elicit key themes. RESULTS: Five main themes (parental experiences of prenatal
      WES, need for information, consent/reasons for prenatal WES, sources of support
      for prenatal WES, and return of WES findings to families) emerged, some with
      multiple subthemes. CONCLUSIONS: Parents desired as much information as possible
      and appreciated information being repeated and provided in various formats. Many
      struggled with clinical uncertainty relating to the cause and prognosis following
      a fetal anomaly diagnosis and found it difficult to balance the risks of invasive
      testing against their need for more definitive information. Parents trusted their
      clinicians and valued their support with decisions in pregnancy. Testing was
      sometimes pursued to reassure parents that their baby was "normal" rather than to
      confirm an underlying genetic problem. Parents were motivated to undergo WES for
      personal and altruistic reasons but disliked waiting times for results and were
      uncertain about what findings might be returned.

PMID- 29049854
TI  - Role of community-based research in advocating HCV prevention and care.

PMID- 29049855
TI  - Intra-arterial transplantation of human bone marrow mesenchymal stem cells
      (hBMMSCs) improves behavioral deficits and alters gene expression in rodent
      stroke model.
AB  - Stroke is a multi-factorial polygenic disease and is a major cause of death and
      adult disability. Administration of bone marrow stem cells protects ischemic rat
      brain by facilitating recovery of neurological functions. But the molecular
      mechanism of stem cells action and their effect on gene expression is not well
      explored. In this study, we have transplanted 1 * 106 human bone marrow
      mesenchymal stem cells (hBMMSCs) in middle cerebral artery occluded (MCAo) adult
      male Wistar rats through intracarotid artery route at 24 h after surgery. Motor
      behavioral tests (rotarod and open field) were performed to assess the changes in
      motor functions at day 0 and day1, 4, 8 and 14. The expression of studied genes
      at mRNA and protein level was quantified by using Q-PCR and western blotting,
      respectively. Further, we have assessed the methylation pattern of promoter of
      these genes by using methylation-specific PCR. Data were analyzed statistically
      and correlated. A significant improvement in behavioral deficits was observed in
      stem cells treated group after 14th day post stroke. Significantly (p < 0.05)
      increased mRNA and protein levels of brain derived neurotrophic factor and ANP
      genes in hBMMSCs treated group along with decrease in methylation level at their
      promoter was observed. On the other hand, significantly decreased mRNA and
      protein level of TSP1 and WNK1 in hBMMSCs treated group was observed. In
      conclusion, hBMMSCs administration significantly improves the behavioral deficits
      by improving motor and locomotor coordination. The promoter of TSP1 and WNK1
      genes was found to be hyper-methylated in hBMMSCs group resulting in their
      decreased expression while the promoter of ANP and brain derived neurotrophic
      factor was found to be hypo-methylated. This study might shed a light on how
      hBMMSCs affect the gene expression by modulating methylation status.

PMID- 29049856
TI  - Is left upper lobectomy always worthwhile for early stage lung cancer? A
      comparison between left upper lobectomy, trisegmentectomy, and lingulectomy.
AB  - BACKGROUND AND OBJECTIVES: Lobectomy is the gold standard treatment for
      resectable Non-Small Cell Lung Cancer (NSCLC). We compared oncological outcomes
      of patients undergoing a "multi-segmentectomy" (trisegmentectomy or lingulectomy)
      and left upper lobectomy for early stage (T1-2, N0) NSCLC of the left upper lobe.
      METHODS: We retrospectively analyzed all patients with pathological early stage
      (T1-T2 N0) NSCLC located in left upper lobe who underwent a lobectomy, a
      trisegmentectomy, or a lingulectomy between 2006 and 2013, focusing on surgical
      and oncological outcomes. RESULTS: Among 159 patients, 105 patients underwent a
      lobectomy and 54 patients a multi-segmentectomy (33 lingulectomy and 21
      trisegmentectomy). Actuarial mean Overall Survival was 87 months (95%CI 79-95)
      and 89 months (95%CI 76-101) for lobectomies and multi-segmentectomies,
      respectively (P-value: 0.895), while actuarial mean Disease Free Interval was 91
      months (95%CI 82-100) and 96 months (95%CI 84-108) respectively (P-value: 0.565).
      We did not observe any difference in terms of local recurrence rate between the
      two groups (P = 0.337). CONCLUSIONS: Lingulectomy and trisegmentectomy lead to
      similar oncological outcomes compared to left upper lobectomy for T1 and T2 N0
      NSCLC, and they could be used as an alternative to lobectomy even in patients
      with a good pulmonary function.

PMID- 29049857
TI  - Local therapy to distant metastatic sites in stage IV rhabdomyosarcoma.
AB  - PURPOSE: To determine the impact of surgery and/or radiation therapy on distant
      metastatic sites (DMS) in children with stage IV rhabdomyosarcoma (RMS). METHODS:
      A retrospective chart review was conducted on all patients with stage IV RMS at
      Texas Children's Hospital from 1992 to 2012. Data analyzed included age, gender,
      primary site, histologic subtype, number and sites of metastases, treatment
      including local therapy to DMS, and Oberlin score. RESULTS: The 5-year
      progression-free survival (PFS) and overall survival (OS) rates were 20% and 25%.
      The 5-year PFS in patients receiving local therapy to all DMS (n = 16) and to
      less than all DMS (n = 19) was 31.3% versus 0% (P = 0.002), whereas the 5-year OS
      was 37.3% versus 0% (P < 0.001), respectively. The 5-year PFS in patients with
      isolated lung metastasis versus other types of metastasis was 29% versus 7% (P =
      n.s.), whereas the 5-year OS was 43% versus 10% (P = 0.01). The 5-year pulmonary
      local control was improved by the use of whole lung irradiation (WLI; 56% vs.
      10%, P = 0.03). CONCLUSIONS: Local treatment to all metastatic sites was
      associated with improved PFS and OS at 5 years. The use of WLI improved pulmonary
      control in patients with lung metastasis. We recommend an aggressive approach
      including local therapy to DMS in children with stage IV RMS.

PMID- 29049858
TI  - Adolescents and young adults with brain tumors in the context of molecular
      advances in neuro-oncology.
AB  - Adolescents and young adults (AYA) comprise a specific group of oncology patients
      with a distinct biological and epidemiological spectrum of central nervous system
      neoplasms. It has been well documented that they differ clinically, especially in
      relation to prognosis and chemotherapy tolerance; however, the underlying reasons
      for this are unclear. Recent advances in the genomics of both childhood and adult
      brain tumors have provided new explanations and insights into the previously
      described age-dependent heterogeneity. Herein, we summarize the current state of
      the AYA population in neuro-oncology, specifically how biological advances can
      help personalize therapy for this unique group of patients.

PMID- 29049859
TI  - "Let them eat strawberries": Dietary restrictions for children with cancer.

PMID- 29049853
TI  - Nutrient-driven O-GlcNAc in proteostasis and neurodegeneration.
AB  - Proteostasis is essential in the mammalian brain where post-mitotic cells must
      function for decades to maintain synaptic contacts and memory. The brain is
      dependent on glucose and other metabolites for proper function and is spared from
      metabolic deficits even during starvation. In this review, we outline how the
      nutrient-sensitive nucleocytoplasmic post-translational modification O-linked N
      acetylglucosamine (O-GlcNAc) regulates protein homeostasis. The O-GlcNAc
      modification is highly abundant in the mammalian brain and has been linked to
      proteopathies, including neurodegenerative diseases such as Alzheimer's,
      Parkinson's, and Huntington's. C. elegans, Drosophila, and mouse models harboring
      O-GlcNAc transferase- and O-GlcNAcase-knockout alleles have helped define the
      role O-GlcNAc plays in development as well as age-associated neurodegenerative
      disease. These enzymes add and remove the single monosaccharide from protein
      serine and threonine residues, respectively. Blocking O-GlcNAc cycling is
      detrimental to mammalian brain development and interferes with neurogenesis,
      neural migration, and proteostasis. Findings in C. elegans and Drosophila model
      systems indicate that the dynamic turnover of O-GlcNAc is critical for
      maintaining levels of key transcriptional regulators responsible for
      neurodevelopment cell fate decisions. In addition, pathways of autophagy and
      proteasomal degradation depend on a transcriptional network that is also reliant
      on O-GlcNAc cycling. Like the quality control system in the endoplasmic reticulum
      which uses a 'mannose timer' to monitor protein folding, we propose that
      cytoplasmic proteostasis relies on an 'O-GlcNAc timer' to help regulate the
      lifetime and fate of nuclear and cytoplasmic proteins. O-GlcNAc-dependent
      developmental alterations impact metabolism and growth of the developing mouse
      embryo and persist into adulthood. Brain-selective knockout mouse models will be
      an important tool for understanding the role of O-GlcNAc in the physiology of the
      brain and its susceptibility to neurodegenerative injury.

PMID- 29049860
TI  - Could we use parent report as a valid proxy of child report on anxiety,
      depression, and distress? A systematic investigation of father-mother-child
      triads in children successfully treated for leukemia.
AB  - BACKGROUND: Systematic assessment of emotional distress is recommended in after
      care. Yet, it is unclear if parent report may be used as a proxy of child report.
      The aim of this study was to assess agreements and differences and explore
      possible moderators of disagreement between child and parent ratings. METHODS:
      Sixty-two young survivors treated for acute lymphoblastic leukemia (9-18 years)
      and both parents responded to the Beck Youth Inventory (anxiety and depression)
      and the distress rating scale on the child's status. Parents completed the Brief
      Symptom Inventory-18 on their own psychological status. Systematic analyses of
      agreement and differences were performed. RESULTS: Mother-child and father-child
      agreements were fair on anxiety, depression, and distress (median intraclass
      correlation coefficient = 0.37). Differences between parents and children were
      medium sized (median d = 0.55) with parents giving higher scores than their
      children on anxiety, depression, and distress. Mothers reported distress more
      frequently than fathers (39 vs. 17%) when children reported none. The child being
      female and lower parental income were associated with lower agreement in fathers
      when rating child distress. Higher levels of parental psychological symptoms were
      consistently associated with lower agreement. CONCLUSIONS: Parent-child
      differences when rating adolescent survivors' difficulties may be more important
      than previously thought. Parent report probably cannot be considered as a valid
      proxy of older child report on such internalized domains as anxiety, depression,
      or distress in the after-care clinic. Parents' report is also likely to be
      influenced by their own mood, a factor that should be corrected for when using
      their report.

PMID- 29049861
TI  - Mifepristone-misoprostol for menstrual regulation in public sector facilities in
      Bangladesh.
AB  - OBJECTIVE: To examine the use of mifepristone and misoprostol for menstrual
      regulation among Bangladeshi women attending public sector facilities. METHODS:
      In a prospective study, women (aged >=18 years) with up to 9 weeks of amenorrhea
      were enrolled at 24 government health facilities in Bangladesh from November 2012
      to June 2015. Paramedics or female welfare visitors provided most menstrual
      regulation care. Participants took 200 mg mifepristone followed by 800 MUg buccal
      misoprostol after 24 hours, and were asked to return to the clinic 10-14 days
      later for clinical assessment and an exit interview. The primary outcome was
      successful evacuation of the uterus without need for surgical intervention. Women
      who completed follow-up were included in analyses for the primary outcome.
      RESULTS: Among 1744 enrolled participants, 1738 completed follow-up. Most (1674,
      96.3%) had a successful uterine evacuation without the need for surgical
      intervention. A successful outcome was significantly more common in primary
      (724/744, 97.3%) and secondary facilities (861/895, 96.2%) than in the specialty
      hospital (89/99, 89.9%; P<0.001 and P=0.004, respectively). CONCLUSION: Menstrual
      regulation with mifepristone and misoprostol can be provided effectively in
      public sector facilities in Bangladesh. CLINICALTRIALS.GOV: NCT01798017.

PMID- 29049862
TI  - Primary mediastinal large B-cell lymphoma: Outcome of a series of pediatric
      patients treated with high-dose methotrexate and cytarabine plus anti-CD20.
AB  - Between 2007 and 2013, 13 children diagnosed with primary mediastinal large B
      cell lymphoma (PMLBL) were treated according to a modified version of AIEOP
      (Associazione Italiana Ematologia Oncologia Pediatrica) LNH-97 protocol based on
      high-dose methotrexate, anthracyclines, and addition of anti-CD20. Ten patients
      achieved a continuous complete remission with front-line therapy. The overall 5
      year survival was 91.7%, and event-free survival was 83.9%, with only one patient
      dying of progressive disease. Despite the few cases, these results demonstrate
      that this therapy, which includes anti-CD20, given in a multicenter setting, is
      feasible with acceptable toxicity in children with PMLBL.

PMID- 29049863
TI  - Reply to: Medication contaminants as a potential cause of anaphylaxis to
      vincristine: What about drug specific antigens?

PMID- 29049864
TI  - Continuation of lithium after a diagnosis of chronic kidney disease.
AB  - OBJECTIVE: To investigate whether continued lithium or anticonvulsant treatment
      after a first diagnosis of chronic kidney disease (CKD) was associated with
      progression to irreversible end-stage kidney disease. METHODS: Nationwide cohort
      study including all individuals in Denmark in a period from 1995 to 2012 with a
      diagnosis of CKD and (i) a history of lithium treatment (N = 754, among whom 238
      patients had a diagnosis of bipolar disorder) or (ii) a history of anticonvulsant
      treatment (N = 5.004, among whom 199 patients had a diagnosis of bipolar
      disorder). End-stage CKD was defined as chronic dialysis or renal
      transplantation. RESULTS: Continuing lithium (HR = 0.58 (95% CI: 0.37-0.90) and
      continuing anticonvulsants (HR = 0.53 (95% CI: 0.44-0.64) were associated with
      decreased rates of end-stage CKD. In the subcohorts of patients with a diagnosis
      of bipolar disorder, continuing lithium was associated with decreased end-stage
      CKD (HR = 0.40 (95% CI: 0.17-0.98), whereas continuing anticonvulsants was not
      (HR = 0.70 (95% CI: 0.21-2.37). There were no interactions of continuing lithium
      and anticonvulsants. CONCLUSION: After an initial diagnosis of CKD, patients who
      are selected by their physicians to continue lithium treatment may not
      necessarily have an increased risk of developing end-stage CKD. Shifting to an
      anticonvulsant per se may not be associated with an advantage; however, this
      requires further investigation.

PMID- 29049866
TI  - Melanoma sponge on pigmentation gene to reduce tumour-suppressive microRNAs.

PMID- 29049865
TI  - Interrogating Membrane Protein Conformational Dynamics within Native Lipid
      Compositions.
AB  - The interplay between membrane proteins and the lipids of the membrane is
      important for cellular function, however, tools enabling the interrogation of
      protein dynamics within native lipid environments are scarce and often invasive.
      We show that the styrene-maleic acid lipid particle (SMALP) technology can be
      coupled with hydrogen-deuterium exchange mass spectrometry (HDX-MS) to
      investigate membrane protein conformational dynamics within native lipid
      bilayers. We demonstrate changes in accessibility and dynamics of the rhomboid
      protease GlpG, captured within three different native lipid compositions, and
      identify protein regions sensitive to changes in the native lipid environment.
      Our results illuminate the value of this approach for distinguishing the putative
      role(s) of the native lipid composition in modulating membrane protein
      conformational dynamics.

PMID- 29049867
TI  - Ion pair and solvation dynamics of [Bmim][BF4 ] + water system.
AB  - In this work, 1-butyl-3-methylimidazolium tetrafluoroborate/water mixtures were
      analysed over the whole water composition (xw ) in order to study the rotational
      and translational behaviour of the ions. We employed a multinuclear NMR approach
      to determine anion/cation/water diffusion coefficients and longitudinal
      relaxation rates at different water content. In neat ionic liquids (IL), the
      cation diffuses faster than the anion, and at low xw , anions and cations share
      almost the same diffusion coefficient, but above a critical water concentration,
      the anion begins to diffuse faster than the cation. We identified this
      composition as approximately 10% xw where the ions share the same diffusion
      coefficient. We found that the water at this composition seems to have a much
      more dramatic effect in the rotational diffusion of the anion that decreases
      substantially and approaches that of the anion in the diluted IL. Translational
      and rotational dynamics of the ions suggest that water is first incorporated in
      pockets in the nanostructure of the IL allowing the ions to maintain most of the
      cation/anion interactions present in neat IL but already disrupting some
      anion/cation interactions due to preferential interaction with the anion. HOESY
      and NOESY data show that water displays contacts both with the cation and the
      anion in a positive NOE regime in contrary to the negative regime found for the
      cation/anion and cation/cation cross-relaxation. This is in accordance with the
      high relative diffusion coefficient of water and suggests that water molecules
      can exchange between preferential location sites that allow water to maintain
      contacts both with the anion and cation.

PMID- 29049868
TI  - A Novel Home-Based Intervention for Child and Adolescent Obesity: The Results of
      the Whanau Pakari Randomized Controlled Trial.
AB  - OBJECTIVE: To report 12-month outcomes from a multidisciplinary child obesity
      intervention program, targeting high-risk groups. METHODS: In this unblinded
      randomized controlled trial, participants (recruited January 2012-August 2014)
      were aged 5 to 16 years, resided in Taranaki, Aotearoa/New Zealand, and had BMI
      >= 98th percentile or BMI > 91st percentile with weight-related comorbidities.
      Randomization was by minimization (age and ethnicity), with participants assigned
      to an intense intervention group (home-based assessments at 6-month intervals and
      a 12-month multidisciplinary program with weekly group sessions) or to a minimal
      intensity control group with home-based assessments and advice at each 6-month
      follow-up. The primary outcome was the change in BMI standard deviation score
      (SDS) at 12 months from baseline. A mixed model analysis was undertaken,
      incorporating all 6- and 12-month data. RESULTS: Two hundred and three children
      were randomly assigned (47% Maori, 43% New Zealand European, 53% female, 28% from
      the most deprived quintile, mean age 10.7 years, mean BMI SDS 3.12). Both groups
      displayed a change in BMI SDS at 12 months from baseline (-0.12 control, -0.10
      intervention), improvements in cardiovascular fitness (P < 0.0001), and
      improvements in quality of life (P < 0.001). Achieving >= 70% attendance in the
      intense intervention group resulted in a change in BMI SDS of -0.22. CONCLUSIONS:
      This program achieved a high recruitment of target groups and a high rate of BMI
      SDS reduction, irrespective of intervention intensity. If retention is optimized,
      the intensive program doubles its effect.

PMID- 29049869
TI  - Collagen vitrigels with low-fibril density enhance human embryonic stem cell
      derived retinal pigment epithelial cell maturation.
AB  - Structural and biochemical cues of extracellular matrix can substantially
      influence the differentiation and maturation of cultured retinal pigment
      epithelial (RPE) cells. In this study, thin collagen vitrigels were engineered to
      create collagen nanofibrillar structures of different fibril densities in an
      effort to evaluate the maturation of human embryonic stem cell-derived retinal
      pigment epithelial (hESC-RPE) cells. The ultrastructure of the different collagen
      vitrigels was characterized by transmission electron microscopy, and the
      mechanical properties were evaluated by tensile testing. The pigmentation and
      polarization of cells, in addition to key RPE marker gene and protein expression
      levels, were analyzed to determine the differentiation of hESCs on the gels. The
      hESC-RPE differentiation was most significant in collagen vitrigels with low
      fibril density with mature collagen fibrils with diameter of around 60 nm and
      Young's modulus of 2.41 +/- 0.13 MPa. This study provides insight into the
      influence of collagen nanofibrillar structures on hESC-RPE maturation and
      presents a potential bioengineered substratum for hESC-RPE for future preclinical
      and clinical applications.

PMID- 29049870
TI  - Dendrimers: Breaking the paradigm of current musculoskeletal autoimmune
      therapies.
AB  - The advances achieved by cell-based therapies to treat autoimmune diseases such
      as rheumatoid arthritis (RA) and multiple sclerosis (MS), despite promising, are
      still insufficient for the current demands. RA and MS therapeutic approaches
      follow world guidelines to use disease modifying drugs and biological agents
      that, regardless of some good results in clinical outcomes, are well known for
      several systemic secondary side effects. Dendrimers are custom-made nanoparticles
      with proved clinical potential, displaying proper size, chemistries,
      immunomodulatory, and anti-inflammatory properties. This has directed their
      potential use as drug delivery systems for cancer therapy, for instance. This
      review manuscript discloses the hidden potential behind dendrimers as alternative
      viable solutions to treat RA and MS, by focusing in the most recent reports
      describing the use of dendrimers for suppressing inflammation and possibly
      preventing disease progression. The advantages of their use as compared with
      current applied therapies is also discussed herein.

PMID- 29049871
TI  - A table-top PXI based low-field spectrometer for solution dynamic nuclear
      polarization.
AB  - We present the development of a portable dynamic nuclear polarization (DNP)
      instrument based on the PCI eXtensions for Instrumentation platform. The main
      purpose of the instrument is for study of 1 H polarization enhancements in
      solution through the Overhauser mechanism at low magnetic fields. A DNP probe set
      was constructed for use at 6.7 mT, using a modified Alderman-Grant resonator at
      241 MHz for saturation of the electron transition. The solenoid for detection of
      the enhanced 1 H signal at 288 kHz was constructed with Litz wire. The largest
      observed 1 H enhancements (epsilon) at 6.7 mT for 14 N-CTPO radical in air
      saturated aqueous solution was epsilon~65. A concentration dependence of the
      enhancement is observed, with maximum epsilon at 5.5 mM. A low resonator
      efficiency for saturation of the electron paramagnetic resonance transition
      results in a decrease in epsilon for the 10.3 mM sample. At high incident powers
      (42 W) and long pump times, capacitor heating effects can also decrease the
      enhancement. The core unit and program described here could be easily adopted for
      multi-frequency DNP work, depending on available main magnets and selection of
      the "plug and play" arbitrary waveform generator, digitizer, and radiofrequency
      synthesizer PCI eXtensions for Instrumentatione cards.

PMID- 29049874
TI  - Balancing Bacteria-Osteoblast Competition through Selective Physical Puncture and
      Biofunctionalization of ZnO/Polydopamine/Arginine-Glycine-Aspartic Acid-Cysteine
      Nanorods.
AB  - Bacterial infection and lack of bone tissue integration are two major concerns of
      orthopedic implants. In addition, osteoinductivity often decreases and toxicity
      may arise when antibacterial agents are introduced to increase the antibacterial
      ability. Here hybrid ZnO/polydopamine (PDA)/arginine-glycine-aspartic acid
      cysteine (RGDC) nanorod (NR) arrays are designed and prepared on titanium (Ti)
      implants to not only enhance the osteoinductivity but also effectively kill
      bacteria simultaneously, which are ascribed to the selective physical puncture
      and the biofunctionalization of ZnO/PDA/RGDC nanorods during the competition
      between bacteria and osteoblasts. That is, owing to the much larger size of
      osteoblasts than bacteria, the hybrid NRs can puncture bacteria but not damage
      osteoblasts. Meanwhile, the cytocompatibility can be enhanced through the
      suppression of both reactive oxygen species and higher Zn2+ concentration by the
      covering of PDA and RGDC. The in vitro results confirm the selective puncture of
      the bacterial membrane and the better osteoinductivity. In vivo tests also show
      much higher antibacterial efficacy of the hybrid NRs with far less amounts of
      lobulated neutrophils and adherent bacteria in the surrounding tissues. In
      addition, the hybrid NRs also accelerate formation of new bone tissues (20.1%
      higher than pure Ti) and osteointegration between implants and newly formed
      tissues (32.0% higher than pure Ti) even in the presence of injected bacteria.
      This work provides a surface strategy for designing implants with desirable
      ability of osseointegration and infection prevention simultaneously, which will
      exhibit tremendous clinical potential in orthopedic and dental applications.

PMID- 29049873
TI  - Association between grade of referral smear and high-grade disease among women
      with biopsy samples showing cervical intraepithelial neoplasia grade 2.
AB  - OBJECTIVE: To determine whether the grade of referral smear reflects the
      frequency of cervical intraepithelial neoplasia (CIN) grade 3 (CIN3) or worse
      lesions among patients with CIN2 on punch biopsy. METHODS: In a retrospective
      study, data were reviewed from women with a punch biopsy sample showing CIN2 and
      a known referral smear who underwent large loop excision of the transformation
      zone (LLETZ) between January 1, 2013, and January 1, 2016, at Galway University
      Hospital, Ireland. Data were analyzed by patient age (<=30 and >30 years),
      referral smear (low and high grade), and LLETZ histology (<=CIN2 and >=CIN3).
      RESULTS: Overall, 264 women were included. LLETZ histology of CIN3 or worse was
      more common among women with high-grade referral smears (63/144 [43.8%]) than
      among those with low-grade smears (26/120 [21.7%]; relative risk 2.02, 95%
      confidence interval 1.37-2.96; P<0.001). Among patients younger than 30 years,
      underlying CIN3 and above was again more frequent among women with high-grade
      (44/95 [46.3%]) versus low-grade smears (12/56 [21.4%]; relative risk 2.16, 95%
      confidence interval 1.25-3.73; P=0.004). No difference was recorded in the older
      age group. CONCLUSION: Although LLETZ can be performed for a CIN2 biopsy and high
      grade smear, consideration should be given among young women (<30 years) with low
      grade smears whose biopsy histology is incidentally CIN2.

PMID- 29049875
TI  - Protocol for the Direct Conversion of Lactones to Lactams Mediated by 1,5,7
      Triazabicyclo[4.4.0]dec-5-ene: Synthesis of Pyridopyrazine-1,6-diones.
AB  - We present an operationally simple lactone-to-lactam transformation utilizing
      diverse amine nucleophiles. The key steps of amidation, alcohol activation, and
      cyclization are all mediated by one reagent (TBD) in a single vessel at room
      temperature. We illustrate the convenience of this protocol by synthesizing a
      wide range of N-alkyl, N-aryl, and N-hetereoaryl pyridopyrazine-1,6-diones, an
      important class of medicinally significant lactams. Furthermore, the reported
      methodology can be applied to the synthesis of milligram to hundred gram
      quantities of pyridopyrazine-1,6-diones without the use of specialized equipment.

PMID- 29049876
TI  - Rational Design of Three-Dimensional Graphene Encapsulated with Hollow FeP@Carbon
      Nanocomposite as Outstanding Anode Material for Lithium Ion and Sodium Ion
      Batteries.
AB  - Transition metal phosphides have been extensively investigated owing to their
      high theoretical capacities and relatively low intercalation potentials vs
      Li/Li+, but their practical applications have been hindered by low electrical
      conductivity and dramatic volume variation during cycling. In this work, an
      interesting strategy for the rational design of graphene (GR) encapsulated with a
      hollow FeP@carbon nanocomposite (H-FeP@C@GR) via a combination of a hydrothermal
      route, a carbon-coating process, phosphidation treatment, and carbothermic
      reaction is reported. The hollow FeP (H-FeP) nanospheres shelled with thin carbon
      layers are wonderfully incorporated into the GR matrix, interconnecting to form a
      three-dimensional (3D) hierarchical architecture. Such a design offers distinct
      advantages for FeP-based anode materials for both lithium ion batteries (LIBs)
      and sodium ion batteries (SIBs). For example, the 3D omnibearing conductive
      networks from the GR skeleton and outer coating carbon can provide an open
      freeway for electron/ion transport, promoting the electrode reaction kinetics. In
      addition, the wrapping of an H-FeP nanosphere in a thin carbon layer enables the
      formation of a solid electrolyte interphase (SEI) on the carbon layer surface
      instead of on the individual H-FeP surface, preventing the continual re-forming
      of the SEI. When used as anode materials for LIBs and SIBs, H-FeP@C@GR exhibited
      excellent electrochemistry performances.

PMID- 29049872
TI  - Optimal dosing and delivery of parathyroid hormone and its analogues for
      osteoporosis and hypoparathyroidism - translating the pharmacology.
AB  - In primary hyperparathyroidism (PHPT), bone loss results from the resorptive
      effects of excess parathyroid hormone (PTH). Under physiological conditions, PTH
      has actions that are more targeted to homeostasis and to bone accrual. The
      predominant action of PTH, either catabolic, anabolic or homeostatic, can be
      understood in molecular and pharmacokinetic terms. When administered
      intermittently, PTH increases bone mass, but when present continuously and in
      excess (e.g. PHPT), bone loss ensues. This dual effect of PTH depends not only on
      the dosing regimen, continuous or intermittent, but also on how the PTH molecule
      interacts with various states of its receptor (PTH/PTHrP receptor) influencing
      downstream signalling pathways differentially. Altering the amino-terminal end of
      PTH or PTHrP could emphasize the state of the receptor that is linked to an
      osteoanabolic outcome. This concept led to the development of a PTHrP analogue
      that interacts preferentially with the transiently linked state of the receptor,
      emphasizing an osteoanabolic effect. However, designing PTH or PTHrP analogues
      with prolonged state of binding to the receptor would be expected to be linked to
      a homeostatic action associated with the tonic secretory state of the parathyroid
      glands that is advantageous in treating hypoparathyroidism. Ideally, further
      development of a drug delivery system that mimics the physiological tonic,
      circadian, and pulsatile profile of PTH would be optimal. This review discusses
      basic, translational and clinical studies that may well lead to newer approaches
      to the treatment of osteoporosis as well as to different PTH molecules that could
      become more advantageous in treating hypoparathyroidism.

PMID- 29049877
TI  - Synthesis of 5'-Thio-3'-O-ribonucleoside Phosphoramidites.
AB  - The chemical synthesis of phosphoramidite derivatives of all four 5'-deoxy-5'
      thioribonucleosides is described. These phosphoramidites contained trityl (A, G,
      C, and U), dimethoxytrityl (A and G), or tert-butyldisulfanyl (G) as the 5'-S
      protecting group. The application of several of these phosphoramidites for solid
      phase synthesis of oligoribonucleotides containing a 2'-O-photocaged 5'-S
      phosphorothiolate linkage or 5'-thiol-labeled RNAs is also further investigated.

PMID- 29049878
TI  - Unifying Exchange Sensitivity in Transition-Metal Spin-State Ordering and
      Catalysis through Bond Valence Metrics.
AB  - Accurate predictions of spin-state ordering, reaction energetics, and barrier
      heights are critical for the computational discovery of open-shell transition
      metal (TM) catalysts. Semilocal approximations in density functional theory, such
      as the generalized gradient approximation (GGA), suffer from delocalization error
      that causes them to overstabilize strongly bonded states. Descriptions of
      energetics and bonding are often improved by introducing a fraction of exact
      exchange (e.g., erroneous low-spin GGA ground states are instead correctly
      predicted as high-spin with a hybrid functional). The degree of spin-splitting
      sensitivity to exchange can be understood based on the chemical composition of
      the complex, but the effect of exchange on reaction energetics within a single
      spin state is less well-established. Across a number of model iron complexes, we
      observe strong exchange sensitivities of reaction barriers and energies that are
      of the same magnitude as those for spin splitting energies. We rationalize trends
      in both reaction and spin energetics by introducing a measure of delocalization,
      the bond valence of the metal-ligand bonds in each complex. The bond valence thus
      represents a simple-to-compute property that unifies understanding of exchange
      sensitivity for catalytic properties and spin-state ordering in TM complexes.
      Close agreement of the resulting per-metal-organic-bond sensitivity estimates,
      together with failure of alternative descriptors demonstrates the utility of the
      bond valence as a robust descriptor of how differences in metal-ligand
      delocalization produce differing relative energetics with exchange tuning. Our
      unified description explains the overall effect of exact exchange tuning on the
      paradigmatic two-state FeO+/CH4 reaction that combines challenges of spin-state
      and reactivity predictions. This new descriptor-sensitivity relationship provides
      a path to quantifying how predictions in transition-metal complex screening are
      sensitive to the method used.

PMID- 29049880
TI  - Crystalline Ordering and Large Fugacity Expansion for Hard-Core Lattice
      Particles.
AB  - Using an extension of Pirogov-Sinai theory, we prove phase transitions,
      corresponding to sublattice orderings, for a general class of hard-core lattice
      particle systems with a finite number of perfect coverings. These include many
      cases for which such transitions have been proven. The proof also shows that for
      these systems the Gaunt-Fisher expansion of the pressure in powers of the inverse
      fugacity (aside from an explicit logarithmic term) has a nonzero radius of
      convergence.

PMID- 29049881
TI  - Effect of the Alkanoyl Group Position at the Glycerol Backbone on the Monolayer
      Characteristics Demonstrated by 2-Monopalmitoyl-rac-glycerol.
AB  - The influence of the position of the aliphatic chain at the glycerol backbone has
      been basically unknown. Solely the results of 2-monopalmitoyl-rac-glycerol
      obtained at >=13  degrees C indicated an essential influence of the position of
      the palmitoyl group at the glycerol backbone, substantiated by a disordered
      packing of the alkyl chains. Therefore, the present study extends the
      comprehensive characterization of 2-monopalmitoyl-rac-glycerol monolayers to the
      low-temperature range for highlighting the effect of the position of the
      aliphatic chain at the glycerol backbone of monoalkanoylglycerolester monolayers.
      Systematic studies of the thermodynamic behavior, the morphological features, and
      the 2D lattice structures of 2-monopalmitoyl-rac-glycerol monolayers at <=10 
      degrees C allow useful conclusions. Large differences between the pi-A isotherms
      of 1- and 2-monopalmitoyl-rac-glycerol monolayers and their thermodynamic
      analysis indicate that the change of the substitution from position 1 to position
      2 of glycerol backbone is consistent with a shortening of the alkyl chain by
      roughly two CH2 groups. Quantum chemical calculations of the molecular structure
      and packing calculations are in reasonable agreement with the thermodynamic
      results. Considerable diversity in the mesoscopic domain topography exists
      between the monoalkanoylglycerol esters with the aliphatic chain positioned at
      the end of the glycerol backbone (1-position) and those with the aliphatic chain
      in the middle of the glycerol backbone (2-position). The new faceted shape of the
      2-monopalmitoyl-rac-glycerol domains, before they develop branched fractal-like
      structures at the edges, is the essential difference to the round or cardioid
      like 1-monoalkanoylglycerol domains. In the low-temperature range, well-defined
      orthorhombic lattice structures exist at all surface pressures. Comparing all
      GIXD data from the three racemic compounds (1-monostearoyl-rac-glycerol, 1
      monopalmitoyl-rac-glycerol, and 2-monopalmitoyl-rac-glycerol) shows that 2
      monopalmitoyl-rac-glycerol behaves as 1-monomyristoyl-rac-glycerol, i.e., the
      shift from position 1 to position 2 of the glycerol backbone is equivalent to a
      shortening of the alkyl chain.

PMID- 29049879
TI  - Width-Dependent Band Gap in Armchair Graphene Nanoribbons Reveals Fermi Level
      Pinning on Au(111).
AB  - We report the energy level alignment evolution of valence and conduction bands of
      armchair-oriented graphene nanoribbons (aGNR) as their band gap shrinks with
      increasing width. We use 4,4"-dibromo-para-terphenyl as the molecular precursor
      on Au(111) to form extended poly-para-phenylene nanowires, which can subsequently
      be fused sideways to form atomically precise aGNRs of varying widths. We measure
      the frontier bands by means of scanning tunneling spectroscopy, corroborating
      that the nanoribbon's band gap is inversely proportional to their width.
      Interestingly, valence bands are found to show Fermi level pinning as the band
      gap decreases below a threshold value around 1.7 eV. Such behavior is of critical
      importance to understand the properties of potential contacts in GNR-based
      devices. Our measurements further reveal a particularly interesting system for
      studying Fermi level pinning by modifying an adsorbate's band gap while
      maintaining an almost unchanged interface chemistry defined by substrate and
      adsorbate.

PMID- 29049882
TI  - Plasmonic Nanochemistry Based on Nanohole Array.
AB  - We show that the growth of Ag nanoparticles (NPs) follows the areas of maximum
      plasmonic field in nanohole arrays (NAs). We thus obtain Ag NP rings not
      connected to the metallic rim of the nanoholes. The photocatalytic effect
      resulting from the enhanced E-field of NAs boosts the reaction and is responsible
      for the site selectivity. The strategy, using plasmonics to control a chemical
      reaction, can be expanded to organic reactions, for example, synthesis of
      polypyrrole. After the NA film is removed, ordered ring-shaped Ag NPs are easily
      obtained, inspiring a facile micropatterning method. Overall, the results
      reported in this work will contribute to the control of chemical reactions at the
      nanoscale and are promising to inspire a facile way to pursue patterned chemical
      reactions.

PMID- 29049883
TI  - Rotational Spectroscopy of p-Toluic Acid and Its 1:1 Complex with Water.
AB  - The structure and internal dynamics of p-toluic acid and its 1:1 complex with
      water were investigated in the gas phase using chirped-pulse and cavity-based
      Fourier transform microwave spectroscopy. One conformer and one isomer were
      identified for the monomer and monohydrate, respectively. In the monohydrate,
      water acts as both a hydrogen bond donor and acceptor, participating in a six
      membered intermolecular ring with the carboxyl group. Both a- and b-type
      transitions were observed for the monomer; only a-type transitions were observed
      for the monohydrate. Rotational transitions of both species show splittings
      originating from methyl internal rotation, for which the potentials include 3-
      and 6-fold symmetry terms of similar amplitude. For the monomer, a few b-type
      transitions are missing, and their intensities were found to be transferred to c
      type transitions with common energy levels, which are otherwise forbidden. No
      splittings attributable to a water internal tunneling motion were observed for
      the monohydrate. Furthermore, the absence of c-type transitions in the spectrum
      of the monohydrate, despite the large MUc dipole moment component of the
      equilibrium geometry obtained by ab initio calculations, is consistent with a
      barrierless wagging motion of the free hydrogen of water, leading to an average
      MUc dipole moment component of zero. These results provide insights regarding the
      interactions between atmospheric p-toluic acid and water in prenucleation
      complexes and at the air-water interface of aqueous aerosols, where p-toluic acid
      may act as a surfactant.

PMID- 29049884
TI  - A Highly Efficient and Robust Cation Ordered Perovskite Oxide as a Bifunctional
      Catalyst for Rechargeable Zinc-Air Batteries.
AB  - Of the various catalysts that have been developed to date for high performance
      and low cost, perovskite oxides have attracted attention due to their inherent
      catalytic activity as well as structural flexibility. In particular, high amounts
      of Pr substitution of the cation ordered perovskite oxide originating from the
      state-of-the-art Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF) electrode could be a good
      electrode or catalyst because of its high oxygen kinetics, electrical
      conductivity, oxygen capacity, and structural stability. However, even though it
      has many favorable intrinsic properties, the conventional high-temperature
      treatment for perovskite synthesis, such as solid-state reaction and combustion
      process, leads to the particle size increase which gives rise to the decrease in
      surface area and the mass activity. Therefore, we prepared mesoporous nanofibers
      of various cation-ordered PrBa0.5Sr0.5Co2-xFexO5+delta (x = 0, 0.5, 1, 1.5, and
      2) perovskites via electrospinning. The well-controlled B-site metal ratio and
      large surface area (~20 m2 g-1) of mesoporous nanofiber result in high
      performance of the oxygen reduction reaction and oxygen evolution reaction and
      stability in zinc-air battery.

PMID- 29049886
TI  - Structure-Activity Relationship Studies of Pyrimido[5,4-b]indoles as Selective
      Toll-Like Receptor 4 Ligands.
AB  - Previous high throughput screening studies led to the discovery of two novel,
      nonlipid-like chemotypes as Toll-like receptor 4 (TLR4) agonists. One of these
      chemotypes, the pyrimido[5,4-b]indoles, was explored for structure-activity
      relationship trends relative to production of TLR4 dependent
      cytokines/chemokines, resulting in a semioptimized lead (compound 1) that
      provided a starting point for further optimization studies. In this report,
      compounds belonging to three areas of structural modification were evaluated for
      biological activity using murine and human TLR4 reporter cells, primary murine
      bone marrow derived dendritic cells, and human peripheral blood mononuclear
      cells. The compounds bearing certain aryl groups at the C8 position, such as
      phenyl (36) and beta-naphthyl (39), had potencies significantly greater than
      compound 1. Compound 36 displayed human TLR4 agonist activity at submicromolar
      concentrations. The computational analysis suggests that the improved potency of
      these C8-aryl derivatives may be the result of additional binding interactions at
      the interface of the TLR4/myeloid differentiation protein-2 (MD-2) complex.

PMID- 29049887
TI  - All-Atom Molecular Dynamics-Based Analysis of Membrane-Stabilizing Copolymer
      Interactions with Lipid Bilayers Probed under Constant Surface Tensions.
AB  - An all-atom phospholipid bilayer and triblock copolymer model was developed for
      molecular dynamics (MD) studies. These were performed to investigate the
      mechanism of interaction between membrane-stabilizing triblock copolymer P188 and
      1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayers under
      applied lateral surface tension (gamma) to model membrane mechanical stress.
      Results showed that P188 insertion is driven by the hydrophobic poly(propylene
      oxide) (PPO) core and dependent on bilayer area per lipid. Moreover, insertion of
      P188 increased the bilayer's resistance to mechanical rupture, as observed by a
      significant increase in the absolute lateral pressure required to disrupt the
      bilayer. To further investigate the specific chemical features of P188 underlying
      membrane stabilizer function, a series of MD simulations with triblock copolymers
      of the same class as P188 but of varying chemical composition and sizes were
      performed. Results showed that triblock copolymer insertion into the lipid
      bilayer is dependent on overall copolymer hydrophobicity, with higher copolymer
      hydrophobicity requiring a reduced bilayer area per lipid ratio for insertion.
      Further analysis revealed that the effect of copolymer insertion on membrane
      mechanical integrity was also dependent on hydrophobicity. Here, P188 insertion
      significantly increased the absolute apparent lateral pressure required to
      rupture the POPC bilayer, thereby protecting the membrane against mechanical
      stress. In marked contrast, highly hydrophobic copolymers decreased the lateral
      pressure necessary for membrane rupture and thus rendering the membrane
      significantly more susceptible to mechanical stress. These new in silico findings
      align with recent experimental findings using synthetic lipid bilayers and in
      muscle cells in vitro and mouse models in vivo. Collectively, these data
      underscore the importance of PEO-PPO-PEO copolymer chemical composition in
      copolymer-based muscle membrane stabilization in vitro and in vivo. All-atom
      modeling with MD simulations holds promise for investigating novel copolymers
      with enhanced membrane interacting properties.

PMID- 29049885
TI  - Recent Advances in the Mass Spectrometry Methods for Glycomics and Cancer.

PMID- 29049888
TI  - Closing-in behavior: Compensation or attraction?
AB  - OBJECTIVE: Closing-in behavior (CIB) defines the abnormal misplacement of the
      copy performance, positioned very closed to or on the top of the model. This
      symptom is observed in graphic copying by patients suffering from different
      neurological diseases, most commonly dementia. The cognitive origins of this
      behavior are still a matter of investigation, and research of the last 10 years
      has been focused on exploring 2 main accounts of CIB, the compensation and the
      attraction hypotheses, providing evidence in both directions. While the first
      account defines CIB as a compensatory strategy to overcome visuospatial and/or
      working memory deficits during copying tasks, the attraction hypothesis looks at
      CIB as primitive default behavior in which attention and action are closely
      coupled and movements are performed toward the focus of attention. METHOD: We
      explored these 2 hypotheses in a sample of patients with and without CIB, and
      controls in 5 experiments: Experiments 1 and 2 tested the attraction hypothesis
      and, respectively, the prediction that CIB can be elicited in a noncopying dual
      task condition loading upon attentional resources or by irrelevant attentional
      grabbing stimuli. The other experiments investigated the compensation hypothesis
      manipulating the distance between model and copying space (Experiment 3), the
      task demand (single or dual task loading on verbal working memory; Experiment 4),
      the task requirements (copying and tracing) and visual demand (visual copy and
      memory; Experiment 5). RESULTS: The results support the attraction hypothesis of
      CIB. CONCLUSIONS: CIB reflects an impairment of the attention and action system,
      rather than a compensatory strategy. (PsycINFO Database Record

PMID- 29049889
TI  - Early metabolic response after resistance exercise with blood flow restriction in
      well-trained men: a metabolomics approach.
AB  - The present study aimed to compare the early metabolic response between high-load
      resistance exercise (HL-RE) and low-load resistance exercise with blood flow
      restriction (LL-BFR). Nine young, well-trained men participated in a randomized
      crossover design in which each subject completed LL-BFR, HL-RE, or condition
      control (no exercise) with a 1-week interval between them. Blood samples were
      taken immediately before and 5 min after the exercise sessions. Nuclear magnetic
      resonance spectroscopy identified and quantified 48 metabolites, 6 of which
      presented significant changes among the exercise protocols. The HL-RE promoted a
      higher increase in pyruvate, lactate, and alanine compared with the LL-BFR and
      the control. HL-RE and LL-BFR promoted a higher increase in succinate compared
      with the control; however, there was no difference between HL-RE and LL-BFR.
      Also, while there was no difference in acetoacetate between HL-RE and LL-BFR, a
      greater decrease was observed in both compared with the control. Finally, LL-BFR
      promoted a greater decrease in choline compared with the control. In conclusion,
      this study provides by metabolomics a new insight in metabolic response between
      LL-BFR and HL-RE by demonstrating a distinct response to some metabolites that
      are not commonly analyzed.

PMID- 29049890
TI  - DNA methylation signatures in peripheral blood mononuclear cells from a lifestyle
      intervention for women at midlife: a pilot randomized controlled trial.
AB  - Physical activity confers many health benefits, but the underlying mechanisms
      require further exploration. In this pilot randomized controlled trial we tested
      the association between longitudinal measures of DNA methylation and changes in
      objective measures, including physical activity, weight loss, and C-reactive
      protein levels in community-dwelling women aged 55 to 70 years. We assessed DNA
      methylation from 20 healthy postmenopausal women, who did not have a mobility
      disability and allocated them to a group-based intervention, Everyday Activity
      Supports You, or a control group (monthly group-based health-related education
      sessions). The original randomized controlled trial was 6 months in duration and
      consisted of nine 2-h sessions that focused on reducing sedentary behaviour for
      the intervention group, or six 1-h sessions that focused on other topics for the
      control group. We collected peripheral blood mononuclear cells, both at baseline
      and 6 months later. Samples were processed using the Illumina 450k Methylation
      array to quantify DNA methylation at >485 000 CpG sites in the genome. There were
      no significant associations between DNA methylation and physical activity, but we
      did observe alterations at epigenetic modifications that correlated with change
      in percent body weight over a 6-month period at 12 genomic loci, 2 of which were
      located near the previously reported weight-associated genes RUNX3 and NAMPT. We
      also generated a potential epigenetic predictor of weight loss using baseline DNA
      methylation at 5 CpG sites. These exploratory findings suggest a potential
      biological link between body weight changes and epigenetic processes.

PMID- 29049892
TI  - Velocity of the muscle tendon unit is sex-dependent and not altered with acute
      static stretch.
AB  - Contraction velocity of a muscle tendon unit (MTU) is dependent upon the
      interrelationship between fascicles shortening and the tendon lengthening.
      Altering the mechanical properties of these tissues through a perturbation such
      as static stretching slows force generation. Females, who have inherently greater
      compliance compared with males, have slower velocity of MTU components. The
      addition of a static stretch might further exacerbate this sex difference. The
      purpose of this study was to investigate the velocity of fascicle shortening and
      tendon lengthening in males and females during isometric maximal voluntary
      contraction (MVC) of the plantar flexors prior to and following an acute static
      stretch. The MTU was imaged with ultrasound and voluntary activation tested with
      twitch interpolation for the 5-s plantar flexion MVC, which proceeded and
      followed an acute stretch. For the 3-min stretch the ankle was passively rotated
      to maximal dorsi-flexion. The males were stronger (128.71 +/- 7.88 Nm) than the
      females (89.92 +/- 4.70 Nm) but voluntary activation did not differ. Tendon
      lengthening velocity (p = 0.001) and fascicle shortening velocity (p = 0.01) were
      faster in males than females. Tendon velocity was positively and significantly
      correlated with fascicle velocity, (r2 = 0.307, p = 0.02). Although sex was
      significant as a predictor (p = 0.05) time was not independently significant.
      Thus, stretch did not alter this relationship in either sex (p = 0.6). The
      velocity of the individual components of the MTU is slower in females when
      compared with males; however, acute stretch does not alter the relationship
      between these components in males or females.

PMID- 29049893
TI  - Fecal microbiota analysis of children with small intestinal bacterial overgrowth
      among residents of an urban slum in Brazil.
AB  - OBJECTIVE: To analyze the fecal microbiota composition of children living in an
      urban slum in Brazil, with or without small intestinal bacterial overgrowth, and
      to investigate the occurrence of stunting and anemia. METHODS: A total of 100
      children were studied, aged 5-11 years, from the municipality of Osasco, Sao
      Paulo. Small intestinal bacterial overgrowth was screened through hydrogen and
      methane breath test with lactulose. Weight and height were measured, and the
      height-for-age and body mass-for-age anthropometric indexes were calculated. The
      occurrence of anemia was investigated by capillary hemoglobin. Analysis of
      bacterial phylum, genus, and species was performed by real-time polymerase chain
      reaction in fecal samples. RESULTS: Small intestinal bacterial overgrowth was
      identified in 61.0% of the children. A lower mean of height-for-age Z-score ([
      0.48+/-0.90] vs. [-0.11+/-0.97]; p=0.027), as well as capillary hemoglobin
      ([12.61+/-1.03g/dL] vs. [13.44+/-1.19g/dL]; p<0.001) was demonstrated in children
      with SIBO when compared with children without small intestinal bacterial
      overgrowth. Children with small intestinal bacterial overgrowth presented a
      higher frequency of Salmonella spp., when compared to those without small
      intestinal bacterial overgrowth (37.7% vs. 10.3%; p=0.002). Higher counts of
      total Eubacteria (p=0.014) and Firmicutes (p=0.038) were observed in children
      without small intestinal bacterial overgrowth; however, a higher count of
      Salmonella (p=0.002) was found in children with small intestinal bacterial
      overgrowth. CONCLUSION: Children who lived in a slum and were diagnosed with
      small intestinal bacterial overgrowth showed lower H/A Z-scores and hemoglobin
      levels. Furthermore, differences were observed in the fecal microbiota of
      children with small intestinal bacterial overgrowth, when compared to those
      without it; specifically, a higher frequency and count of Salmonella, and lower
      counts of Firmicutes and total Eubacteria.

PMID- 29049895
TI  - Variability in Care-What Would Business People Think?

PMID- 29049894
TI  - Alcohol expectancies longitudinally predict drinking and the alcohol myopia
      effects of relief, self-inflation, and excess.
AB  - INTRODUCTION: Alcohol myopia theory posits that alcohol consumption attenuates
      information processing capacity, and that expectancy beliefs together with intake
      level are responsible for experiences in myopic effects (relief, self-inflation,
      and excess). METHODS: Adults (N=413) averaging 36.39 (SD=13.02) years of age
      completed the Comprehensive Effects of Alcohol questionnaire at baseline,
      followed by alcohol use measures (frequency and quantity) and the Alcohol Myopia
      Scale one month later. Three structural equation models based on differing
      construct manifestations of alcohol expectancies served to longitudinally
      forecast alcohol use and myopia. RESULTS: In Model 1, overall expectancy
      predicted greater alcohol use and higher levels of all three myopic effects. In
      Model 2, specifying separate positive and negative expectancy factors, positive
      but not negative expectancy predicted greater use. Furthermore, positive
      expectancy and use explained higher myopic relief and higher self-inflation,
      whereas positive expectancy, negative expectancy, and use explained higher myopic
      excess. In Model 3, the seven specific expectancy subscales (sociability, tension
      reduction, liquid courage, sexuality, cognitive and behavioral impairment, risk
      and aggression, and self-perception) were simultaneously specified as predictors.
      Tension reduction expectancy, sexuality expectancy, and use contributed to higher
      myopic relief; sexuality expectancy and use explained higher myopic self
      inflation; and risk and aggression expectancy and use accounted for higher myopic
      excess. Across all three predictive models, the total variance explained ranged
      from 12 to 19% for alcohol use, 50 to 51% for relief, 29 to 34% for self
      inflation, and 32 to 35% for excess. CONCLUSIONS: Findings support that the type
      of alcohol myopia experienced is a concurrent function of self-fulfilling alcohol
      prophecies and drinking levels. The interpreted measurement manifestation of
      expectancy yielded different prevention implications.

PMID- 29049896
TI  - Fabrication and photoelectric properties of bio-inspired honeycomb film based on
      semiconducting polymer.
AB  - Organic semiconducting materials have attracted significant attention for use in
      optoelectronic devices, as they can significantly improve device performance.
      Herein, a donor-acceptor conjugated polymer (poly(isoindigo
      thiopheneylbenzothiadiazole, PID-TBT) was synthesized, which has strong and broad
      absorption in the visible region (400-800nm). The band gap of PID-TBT is 1.65eV.
      The PID-TBT honeycomb film with a porous structure was easily fabricated by the
      breath figure method. Compared with the smooth PID-TBT film, the honeycomb film
      shows significant enhancement in light capture capability and the efficiency of
      photoelectric conversion. The reflectance of the honeycomb film is reduced by 7%
      and the photocurrent is tenfold higher than that of the smooth film. Apart from
      designing new molecules by complex reactions, this work demonstrated that
      photoelectric conversion can be easily improved by introducing micro or
      nanostructures into devices.

PMID- 29049897
TI  - Nonenzymatic flexible field-effect transistor based glucose sensor fabricated
      using NiO quantum dots modified ZnO nanorods.
AB  - Herein, we fabricated nonenzymatic flexible field-effect transistor (f-FET) based
      glucose sensor using nickel oxide quantum dots (NiO QDs) modified zinc oxide
      nanorods (ZnO NRs). The ZnO NRs surfaces were coated with NiO QDs using radio
      frequency (RF) magnetron sputtering to enhance the electrocatalytic feature and
      the surface area of ZnO NRs. Under physiological conditions (pH 7.4), the
      nonenzymatic f-FET glucose sensor shows two linear ranges of 0.001-10mM and 10
      50mM with the high sensitivity of 13.14MUAcm-2mM-1 and 7.31MUAcm-2mM-1,
      respectively, along with good selectivity, stability and repeatability during
      glucose detection. The examination of human whole blood and serum samples reveal
      that the nonenzymatic f-FET based glucose sensor is capable of measuring glucose
      concentration efficiently in the presence of interfering species and thus can be
      offered as a promising device for further applications in clinical and non
      clinical fields.

PMID- 29049898
TI  - In-situ gelation of sodium alginate supported on melamine sponge for efficient
      removal of copper ions.
AB  - Sodium alginate-melamine sponge composites were fabricated by in-situ gelation of
      sodium alginate supported on the commercial melamine sponge (MS). MS serves as
      the three-dimensional skeleton for alginate coating and can effectively avoid the
      shrink of alginate, and thus makes the alginate-MS composites user-friendly and
      facile to recover. In the adsorption test, the adsorption process is pseudo
      second order and matches the Langmuir model with the maximum adsorption capacity
      of 90.1mg/g for copper ions. The alginate-MS is recyclable and presents enhanced
      mechanical properties compared with those of pristine MS. All these properties
      make such alginate-MS a promising candidate as an adsorbent for heavy metal
      removal.

PMID- 29049899
TI  - Intraosseous Hemangioma of the Frontal Bone. Report of a Case and Review of the
      Literature.
AB  - Intraosseous hemangiomas of the maxillofacial region are rare lesions that
      constitute less than 1% of all osseous tumors. A review of the literature on
      intraosseous hemangiomas of the skull and facial bones showed a limited number of
      publications, much of which were largely limited to case reports. This case
      report summarizes the workup and surgical treatment of a 39-year-old woman with
      an intraosseous hemangioma of the left frontal bone. The histology, treatment,
      and literature are reviewed.

PMID- 29049900
TI  - Genetic alphabet expansion biotechnology by creating unnatural base pairs.
AB  - Recent studies have made it possible to expand the genetic alphabet of DNA, which
      is originally composed of the four-letter alphabet with A-T and G-C pairs, by
      introducing an unnatural base pair (UBP). Several types of UBPs function as a
      third base pair in replication, transcription, and/or translation. Through the
      UBP formation, new components with different physicochemical properties from
      those of the natural ones can be introduced into nucleic acids and proteins site
      specifically, providing their increased functionalities. Here, we describe the
      genetic alphabet expansion technology by focusing on three types of UBPs, which
      were recently applied to the creations of DNA aptamers that bind to proteins and
      cells and semi-synthetic organisms containing DNAs with a six-letter alphabet.

PMID- 29049901
TI  - The efficacy of aerobic exercise and resistance training as transdiagnostic
      interventions for anxiety-related disorders and constructs: A randomized
      controlled trial.
AB  - Evidence supports exercise as an intervention for many mental health concerns;
      however, randomized controlled investigations of the efficacy of different
      exercise modalities and predictors of change are lacking. The purposes of the
      current trial were to: (1) quantify the effects of aerobic exercise and
      resistance training on anxiety-related disorder (including anxiety disorders,
      obsessive-compulsive disorder, and posttraumatic stress disorder) status,
      symptoms, and constructs, (2) evaluate whether both modalities of exercise were
      equivalent, and (3) to determine whether exercise enjoyment and physical fitness
      are associated with symptom reduction. A total of 48 individuals with anxiety
      related disorders were randomized to aerobic exercise, resistance training, or a
      waitlist. Symptoms of anxiety-related disorders, related constructs, and exercise
      enjoyment were assessed at pre-intervention and weekly during the 4-week
      intervention. Participants were further assessed 1-week and 1-month post
      intervention. Both exercise modalities were efficacious in improving disorder
      status. As well, aerobic exercise improved general psychological distress and
      anxiety, while resistance training improved disorder-specific symptoms, anxiety
      sensitivity, distress tolerance, and intolerance of uncertainty. Physical fitness
      predicted reductions in general psychological distress for both types of exercise
      and reductions in stress for aerobic exercise. Results highlight the efficacy of
      different exercise modalities in uniquely addressing anxiety-related disorder
      symptoms and constructs.

PMID- 29049902
TI  - Emotion dysregulation moderates the effect of cognitive behavior therapy with
      prolonged exposure for co-occurring PTSD and substance use disorders.
AB  - A goal of clinical trials is to identify unique baseline characteristics that can
      inform treatment planning. One such target is emotion dysregulation (ED), which
      contributes to the maintenance of co-occurring posttraumatic stress disorder
      (PTSD) and substance use disorder (SUD) and may be a potential moderator of
      treatment response. We examined the moderating impact of ED severity on treatment
      outcomes in an urban, socioeconomically disadvantaged, and racially/ethnically
      diverse sample with complex trauma and severe SUDs. Participants with co
      occurring PTSD and SUD (PTSD+SUD) were randomized to Concurrent Treatment with
      Prolonged Exposure (COPE, n=39), Relapse Prevention Therapy (RPT, n=43), or an
      active monitoring control group (AMCG, n=28). Baseline ED severity moderated
      treatment outcomes such that high ED was associated with greater reduction in
      PTSD severity among those who received COPE relative to RPT and AMCG. In
      contrast, low ED was associated with greater reduction in substance use among
      those in RPT relative to COPE and AMCG. Implications for individualizing and
      optimizing treatment selection for PTSD+SUD are discussed.

PMID- 29049904
TI  - The impact of Medicare Part D on cognitive functioning at older ages.
AB  - Research has shown that the establishment of Medicare prescription drug benefit
      in 2006 leads to improvement in medication adherence and mortality outcomes.
      Despite a clear connection between physical/mental health and the risk of
      dementia, little is known about the extent to which this reform has affected the
      cognitive functioning of the elderly. Using data from the Health and Retirement
      Study and difference-in-differences approach, this study provides the first
      evidence on the cognition-enhancing effects of Medicare Part D. Our estimates
      show that Part D implementation is associated with 1.6% increase in cognitive
      functioning or 1.1-year delay of cognitive aging among benefit-eligible persons.
      Further analyses indicate that most of the cognitive benefits accrue to the
      vulnerable populations who previously lacked prescription drug coverage, and that
      a reduction in cardiovascular mortality is the most likely pathway through which
      the expansion improved cognitive functioning.

PMID- 29049903
TI  - Glutamate homeostasis in the adult rat prefrontal cortex is altered by cortical
      docosahexaenoic acid accrual during adolescence: An in vivo1H MRS study.
AB  - Major psychiatric disorders are associated with dysregulated glutamate
      homeostasis and deficits in the omega-3 fatty acid docosahexaenoic acid (DHA).
      This study determined the effects of dietary-induced alterations in brain DHA
      accrual on cortical glutamate homeostasis in the adult rat brain. Adolescent rats
      were fed a control diet (n = 20), a n-3 fatty acid-deficient diet (DEF, n = 20),
      or a fish oil-fortified diet containing preformed DHA (FO, n = 20). In adulthood
      1H MRS scans were performed with voxels in the prefrontal cortex (PFC) and
      thalamus. Compared with controls, erythrocyte, PFC, and thalamus DHA levels were
      significantly lower in DEF rats and significantly higher in FO rats. In the PFC,
      but not the thalamus, glutamate was significantly elevated in DEF rats compared
      with controls and FO rats. Glutamine did not differ between groups and the
      glutamine/glutamate ratio was lower in DEF rats. No differences were observed for
      markers of excitotoxicity (NAA, GFAP), or astrocyte glutamate transporter (GLAST,
      GLT-1) or glutamine synthetase expression. Across diet groups, PFC DHA levels
      were inversely correlated with PFC glutamate levels and positively correlated
      with GLAST expression. Together these findings demonstrate that rat cortical DHA
      accrual during adolescence impacts glutamate homeostasis in the adult PFC.

PMID- 29049905
TI  - A case of midazolam anaphylaxis during a pediatric patient's first anesthetic.

PMID- 29049906
TI  - Interaction between compound genetic risk for schizophrenia and high birth weight
      contributes to social anhedonia and schizophrenia in women.
AB  - Schizophrenia is a highly heritable disease, but despite extensive study, its
      genetic background remains unresolved. The lack of environmental measures in
      genetic studies may offer some explanation. In recent Finnish studies, high birth
      weight was found to increase the risk for familial schizophrenia. We examined the
      interaction between a polygenic risk score for schizophrenia and high birth
      weight on social anhedonia and schizophrenia in a general population birth
      cohort. The study sample included 4223 participants from the 1966 Northern
      Finland Birth Cohort. As a replication sample we used 256 participants from a
      systematically collected sample of Finnish schizophrenia families. The polygenic
      risk score comprised of variants published in the large genome-wide meta-analysis
      for schizophrenia. We found the association between the polygenic risk score and
      social anhedonia stronger among those with high birth weight, and the same
      phenomenon was seen for schizophrenia among women, suggesting a gene-environment
      interaction. Similar results were found within the replication sample. Our
      results suggest a role for gene-environment interactions in assessing the risk of
      schizophrenia. Failure to take environmental effects into account may be one of
      the reasons why identifying significant SNPs for schizophrenia in genome-wide
      studies has been challenging.

PMID- 29049907
TI  - Clinical correlates of saccadic eye movement in antipsychotic-naive
      schizophrenia.
AB  - Some aspects of saccadic performance have been found to be abnormal in chronic
      schizophrenia. The majority of this research has, however, been performed on
      patients treated with long-term antipsychotic medication. Very few studies have
      examined saccadic performance in antipsychotic-naive/free patients. There are
      also very few studies describing the relationship between saccadic performance
      and clinical symptoms, particularly in antipsychotic free patients. In this
      study, we compared pro and antisaccade performance in a large sample of
      antipsychotic-naive/free schizophrenia patients (N = 45) with healthy controls (N
      = 57). Clinical symptoms were assessed using Scale for Assessment of Positive
      Symptoms (SAPS) and Negative Symptoms (SANS). In the antisaccade task, patients
      made significantly more errors, and their correct antisaccades had smaller
      amplitudes in comparison to healthy controls. Higher error rates were associated
      with increased severity of hallucinations. In the prosaccade task, patients had
      less accurate final eye positions, and made saccades with slower latency and
      reduced amplitude compared to the healthy controls. These observations in
      schizophrenia patients without the potential confounds of antipsychotic treatment
      suggest intrinsic link between saccadic deficits and schizophrenia pathogenesis.
      The relationship between antisaccade errors and hallucination severity supports
      the potential link between hallucinations and deficits in inhibitory control.

PMID- 29049908
TI  - Feature selection method based on support vector machine and shape analysis for
      high-throughput medical data.
AB  - Proteomics data analysis based on the mass-spectrometry technique can provide a
      powerful tool for early diagnosis of tumors and other diseases. It can be used
      for exploring the features that reflect the difference between samples from high
      throughput mass spectrometry data, which are important for the identification of
      tumor markers. Proteomics mass spectrometry data have the characteristics of too
      few samples, too many features and noise interference, which pose a great
      challenge to traditional machine learning methods. Traditional unsupervised
      dimensionality reduction methods do not utilize the label information
      effectively, so the subspaces they find may not be the most separable ones of the
      data. To overcome the shortcomings of traditional methods, in this paper, we
      present a novel feature selection method based on support vector machine (SVM)
      and shape analysis. In the process of feature selection, our method considers not
      only the interaction between features but also the relationship between features
      and class labels, which improves the classification performance. The experimental
      results obtained from four groups of proteomics data show that, compared with
      traditional unsupervised feature extraction methods (i.e., Principal Component
      Analysis - Procrustes Analysis, PCA-PA), our method not only ensures that fewer
      features are selected but also ensures a high recognition rate. In addition,
      compared with the two kinds of multivariate filter methods, i.e., Max-Relevance
      Min-Redundancy (MRMR) and Fast Correlation-Based Filter (FCBF), our method has a
      higher recognition rate.

PMID- 29049909
TI  - Automatic selection of localized region-based active contour models using image
      content analysis applied to brain tumor segmentation.
AB  - Brain tumor segmentation is a routine process in a clinical setting and provides
      useful information for diagnosis and treatment planning. Manual segmentation,
      performed by physicians or radiologists, is a time-consuming task due to the
      large quantity of medical data generated presently. Hence, automatic segmentation
      methods are needed, and several approaches have been introduced in recent years
      including the Localized Region-based Active Contour Model (LRACM). There are many
      popular LRACM, but each of them presents strong and weak points. In this paper,
      the automatic selection of LRACM based on image content and its application on
      brain tumor segmentation is presented. Thereby, a framework to select one of
      three LRACM, i.e., Local Gaussian Distribution Fitting (LGDF), localized Chan
      Vese (C-V) and Localized Active Contour Model with Background Intensity
      Compensation (LACM-BIC), is proposed. Twelve visual features are extracted to
      properly select the method that may process a given input image. The system is
      based on a supervised approach. Applied specifically to Magnetic Resonance
      Imaging (MRI) images, the experiments showed that the proposed system is able to
      correctly select the suitable LRACM to handle a specific image. Consequently, the
      selection framework achieves better accuracy performance than the three LRACM
      separately.

PMID- 29049910
TI  - An improved synchronization likelihood method for quantifying neuronal synchrony.
AB  - Indirect quantification of the synchronization between two dynamical systems from
      measured experimental data has gained much attention in recent years, especially
      in the computational neuroscience community where the exact model of the neuronal
      dynamics is unknown. In this regard, one of the most promising methods for
      quantifying the interrelationship between nonlinear non-stationary systems is
      known as Synchronization Likelihood (SL), which is based on the likelihood of the
      auto-recurrence of embedding vectors (similar patterns) in multiple dynamical
      systems. However, synchronization likelihood method uses the Euclidean distance
      to determine the similarity of two patterns, which is known to be sensitive to
      outliers. In this study, we propose a discrete synchronization likelihood (DSL)
      method to overcome this limitation by using the Manhattan distance in the
      discrete domain (l1 norm on discretized signals) to identify the auto-recurrence
      of embedding vectors. The proposed method was tested using unidirectional and
      bidirectional identical/non-identical coupled Henon Maps, a Watts-Strogatz small
      world network with nonlinearly coupled nodes based on Kuramoto model and the real
      world ADHD-200 fMRI benchmark dataset. According to the results, the proposed
      method shows comparable and in some cases better performance than the
      conventional SL method, especially when the underlying highly connected coupled
      dynamical system goes through subtle changes in the bivariate case or sudden
      shifts in the multivariate case.

PMID- 29049911
TI  - In-human subject-specific evaluation of a control-theoretic plasma volume
      regulation model.
AB  - The goal of this study was to conduct a subject-specific evaluation of a control
      theoretic plasma volume regulation model in humans. We employed a set of clinical
      data collected from nine human subjects receiving fluid bolus with and without co
      administration of an inotrope agent, including fluid infusion rate, plasma
      volume, and urine output. Once fitted to the data associated with each subject,
      the model accurately reproduced the fractional plasma volume change responses in
      all subjects: the error between actual versus model-reproduced fractional plasma
      volume change responses was only 1.4 +/- 1.6% and 1.2 +/- 0.3% of the average
      fractional plasma volume change responses in the absence and presence of inotrope
      co-administration. In addition, the model parameters determined by the subject
      specific fitting assumed physiologically plausible values: (i) initial plasma
      volume was estimated to be 36 +/- 11 mL/kg and 37 +/- 10 mL/kg in the absence and
      presence of inotrope infusion, respectively, which was comparable to its actual
      counterpart of 37 +/- 4 mL/kg and 43 +/- 6 mL/kg; (ii) volume distribution ratio,
      specifying the ratio with which the inputted fluid is distributed in the intra-
      and extra-vascular spaces, was estimated to be 3.5 +/- 2.4 and 1.9 +/- 0.5 in the
      absence and presence of inotrope infusion, respectively, which accorded with the
      experimental observation that inotrope could enhance plasma volume expansion in
      response to fluid infusion. We concluded that the model was equipped with the
      ability to reproduce plasma volume response to fluid infusion in humans with
      physiologically plausible model parameters, and its validity may persist even
      under co-administration of inotropic agents.

PMID- 29049912
TI  - Globular chitosan treatment of bovine jugular veins: evidence of
      anticalcification efficacy in the subcutaneous rat model.
AB  - Vascular xenografts are widely used in cardiovascular surgery as an alternative
      to autologous vessels and vascular allografts. Calcification is one of the main
      drawbacks of vascular grafts, especially among young patients and children. Among
      different anticalcification approaches, chitosan emerges as a highly promising
      candidate due to its versatility, natural origin, and biocompatibility. We
      investigated the anticalcification efficacy of globular chitosan ("Chitozol") as
      it demonstrated the improved rate of water solubility as compared with
      conventional linear macromolecules of chitosan. In addition, we supposed that
      compact globular form of "Chitozol" molecules could provide effective penetration
      of extracellular matrix of bovine jugular veins (BJVs). Our results revealed that
      "Chitozol" treatment mitigated calcification in the experimental groups as
      compared to the control groups (without any treatment, conventional treatment
      with glutaraldehyde, and commercially available Contegra conduit). Different
      concentrations of "Chitozol" (0.3% and 3%), as well as different incubation times
      (15 and 30min), were equally effective in the prevention of calcification. In
      addition, "Chitozol" treatment with decellularization of BJVs demonstrated
      slightly improved stress-strain properties of unimplanted samples. Thus, the
      filling of fresh BJV with globular chitosan is proposed as a promising emerging
      treatment for the mitigation of calcific degeneration in BJVs xenografts.

PMID- 29049913
TI  - Social class and policy preferences: implications for economic inequality and
      interclass relations.
AB  - Record-setting levels of income and wealth inequality are deepening social class
      divisions. The adoption of strong progressive redistributive policies is crucial
      to reducing class inequities, yet many barriers to doing so exist. This review
      examines class-based policy preferences, focusing on the effects of economic self
      interest, system justification, and classist, racist, and sexist stereotypes on
      policy support. The impact of broader economic conditions is also considered.
      Collectively, this body of research makes clear that building stronger cross
      class support for redistributive policies and programs will prove difficult
      without addressing both class-based power differences and beliefs that justify
      inequality. Reducing stereotypes and developing a shared sense of societal
      responsibility that cuts across class lines can help advance these goals. Social
      psychological research is vital to informing these efforts.

PMID- 29049914
TI  - T-2 toxin induces cytotoxicity and disrupts tight junction barrier in SerW3
      cells.
AB  - T-2 toxin, which is produced in grain and grain products as a secondary
      metabolite by Fusarium species, is also potentially dangerous for human health.
      Up to date, no study was reported the cytotoxicity of T-2 toxin on SerW3 cells in
      the perspective of junctional barriers. This study focused on revealing the
      cytotoxic effects of T-2 on Sertoli cells associated with cell junctional
      barriers. In the present study, SerW3 cells were exposed to T-2 toxin at 12, 120
      and 1200ng/ml doses for 24 and 48h. Cytotoxicity tests including cell viability
      (MTT), lactate dehydrogenase (LDH) cytotoxicity test and trypan blue exclusion
      assay were performed. Occludin, ZO-1, N-cadherin and beta-catenin were
      immunolabelled, expressions of occludin and N-cadherin were determined by western
      blotting. SerW3 cell barrier integrity was measured by transepithelial electrical
      resistance (TEER). Cytotoxicity caused by T-2 toxin increased in a dose dependent
      manner, expressions of proteins and TEER measurement decreased. This study may
      underlie the early targets of T-2 toxin on SerW3 cells mimicking blood-testis
      barrier in vitro.

PMID- 29049915
TI  - Adult primary cervical extra-osseous Ewing's sarcoma: A case report and short
      literature review.
AB  - INTRODUCTION: Primary spinal epidural extraskeletal Ewing's sarcoma (EES) is
      extremely rare, with a peak incidence in the second decade of life. EES in old
      people is challenging to treat due to the lack of specific guidelines. In this
      paper, I present a unique case of adult primary cervical epidural EES with a 13
      month follow-up. A short literature review of the therapeutic approaches and
      prognosis is also presented. PRESENTATION OF CASE: I present a case of a 49-year
      old male patient who presented with right upper limb pain, numbness, hand grip
      weakness, and hyperreflexia of 3 months duration. Enhanced cervical magnetic
      resonance imaging showed a homogenously enhancing epidural and paravertebral soft
      tissue mass extending from the C6 to the T2 that appeared hypointense on T1 and
      hyperintense on T2. The patient underwent biopsy that confirmed EES via
      histopathology. Treatment with chemotherapy and radiotherapy resulted in tumor
      resolution and symptom relief. DISCUSSION: EES is a type of PNET. Surgical
      removal is generally the treatment of choice, followed by adjunctive chemotherapy
      and radiotherapy. In old patients with large tumors, a more conservative approach
      with biopsy, adjuvant chemotherapy and radiotherapy is recommended. CONCLUSIONS:
      Adult primary cervical epidural EES is a neurosurgical challenge due to the
      extension to the surrounding vital structures making the tumor not amenable for
      total resection as in the present case. In the absence of specific therapeutic
      guidelines, our case highlights the need to individualize the treatment modality
      according to age, tumor extension, and feasibility of total tumor resection.

PMID- 29049916
TI  - Immune cell type 'fingerprints' at the basis of outcome diversity of human
      infection.
AB  - Despite the availability of antibiotics and immunization, infectious diseases
      remain a major cause of malignancy and death worldwide. Yet, it is well
      documented that for most infectious agents, clinical disease develops in only a
      small minority of infected individuals. There is, in fact, great heterogeneity in
      infection outcome, from complete clearance of the pathogen to severe illness.
      Understanding this variation remains elusive, despite its great potential to
      equip us with new tools for the treatment of infectious diseases. Here, we
      propose a novel perspective for studying this diversity in human infection
      outcome, one that utilizes single-cell analysis technologies. Recent advances in
      single-cell RNA-seq technologies allow the detection of rare subpopulations that
      play important roles in host-pathogen interactions. We propose that applying
      single-cell RNA-seq to the study of infection can provide a 'fingerprint' of the
      immune cell types that are associated with the ability of the host to clear a
      pathogen and, thereby, broaden our current understanding of variation in
      susceptibility to infection within the population.

PMID- 29049917
TI  - Response to culturally competent drug treatment among homeless persons with
      different living arrangements.
AB  - This study investigated the association between program cultural competence and
      homeless individuals' drug use after treatment in Los Angeles County, California.
      Los Angeles County has the largest and most diverse population of homeless
      individuals in the nation. We randomly selected for analysis 52 drug-treatment
      programs and 2158 participants who identified as homeless in the Los Angeles
      County Participant Reporting System in 2011. We included their living
      arrangements (indoors and stable, indoors and unstable, and outdoors) and
      individual and program characteristics (particularly whether their programs used
      six culturally competent practices) in multilevel regression analyses. The
      outcome was days of primary drug use at discharge.Results showed that higher
      levels of staff personal involvement in minority communities (IRR=0.437; 95%
      CI=0.222, 0.861) and outreach to minority communities (IRR = 0.406; 95% CI=0.213,
      0.771) were associated with fewer days of drug use at discharge. Homeless
      individuals living outdoors used their primary drug more often than any other
      group. Yet, compared to individuals with other living arrangements, when outdoor
      homeless individuals were treated by programs with the highest community
      resources and linkages (IRR=0.364; 95% CI=0.157, 0.844), they reported the fewest
      days of drug use. We discuss implications for program evaluation and community
      engagement policies and practices.

PMID- 29049918
TI  - DC-SIGN expression in Hofbauer cells may play an important role in immune
      tolerance in fetal chorionic villi during the development of preeclampsia.
AB  - Immune tolerance at feto-maternal interfaces is a complex phenomenon. Although
      maternal decidual macrophages are well-known immune cells, little is known about
      fetal-derived macrophages (Hofbauer cells) within chorionic villi. Preeclampsia
      (PE) is a major cause of maternal mortality in the field of obstetrics, and the
      innate immunological role of maternal decidual macrophages is well known. In this
      study, we assessed the differential phenotypes and marker expression in fetal
      macrophages, known as dendritic cell-specific ICAM-grabbing non-integrin (DC
      SIGN)-positive Hofbauer cells. We compared Hofbauer cell properties between
      normal and PE placenta chorionic villi and performed sequential staining of DC
      SIGN, CD14, and CD68 to evaluate the existence of Hofbauer cells. Furthermore, to
      evaluate the immunological function of these cells, we stained the cells for
      CD163, a marker of immunoregulatory type 2 (M2) macrophages. Additionally, we
      examined the expression of the immunosuppressive cytokine interleukin (IL)-10,
      which is known to be produced by M2 macrophages. DC-SIGN+/CD14+, DC-SIGN+/CD68+,
      and CD163+/DC-SIGN+ cells were quantified based on photomicrographs. The results
      showed that CD14, CD163, DC-SIGN, and IL-10 levels were significantly
      downregulated in PE compared with normal. Additionally, CD163+/DC-SIGN+ Hofbauer
      cells were significantly less frequent in PE than in normal. DC-SIGN Hofbauer
      cells produced IL-10 at lower levels in the PE than in the normal. Thus, we
      speculate that fetal-derived Hofbauer cells may play an important role in normal
      pregnancy with immunosuppressive effects based on their M2 macrophage
      characteristics to maintain immune tolerance during pregnancy. Additionally, in
      PE, these functions were defective, supporting the roles of these macrophages in
      PE development.

PMID- 29049919
TI  - Comparison of CHA2DS2-VASc, CHADS2 and HATCH scores for the prediction of new
      onset atrial fibrillation in cancer patients: A nationwide cohort study of
      760,339 study participants with competing risk analysis.
AB  - BACKGROUND AND AIMS: The current study was conducted to assess the ability of
      CHA2DS2-VASc, CHADS2 and HATCH scores in predicting new-onset atrial fibrillation
      (AF) among patients with cancer. METHODS: Patients with newly diagnosed cancer
      between 1 January, 2000 and 31 December, 2011, from the Registry for Catastrophic
      Illness Patient Database, were defined as the study cohort. CHA2DS2-VASc, CHADS2
      and HATCH scores were used for new-onset AF prediction in these study patients,
      and the predictive accuracy of the scores was assessed by the receiver operating
      characteristics (ROC) curve. RESULTS: A total of 760,339 cancer patients were
      identified as the study participants. The ROC curves were 0.68 (95% confidence
      interval [CI] = 0.68-0.69) for the CHA2DS2-VASc score, 0.67 (95% CI = 0.67-0.68)
      for the CHADS2 score and 0.69 (95% CI = 0.69-0.70) for the HATCH score. There
      were significant differences of c-statistics among CHA2DS2-VASc score, CHADS2
      score and HATCH score (CHA2DS2-VASc score vs. CHADS2 score, p = 0.01; CHA2DS2
      VASc score vs. HATCH score, p = 0.002; CHADS2 score vs. HATCH score, p < 0.001).
      CONCLUSIONS: The current study is the first to assess the prognostic value of 3
      AF risk scores (CHA2DS2-VASc, CHADS2 and HATCH scores) in patients with newly
      diagnosed cancer. HATCH score was found to have a slightly but significantly
      better predictive performance than the other 2 scores.

PMID- 29049920
TI  - Factors associated with vision-related quality of life among the adult population
      living in Nagorno Karabagh.
AB  - OBJECTIVES: Visual impairment and blindness are major public health problems
      causing significant suffering, disability, loss of productivity, and diminishing
      quality of life for millions of people. This study explored the factors
      associated with the overall vision-related quality of life (VRQoL) and its
      different domains in the adult population of Nagorno Karabakh and assessed the
      independent contribution of specific eye diseases to VRQoL. STUDY DESIGN: A cross
      sectional study. METHODS: We conducted interviewer-administered survey along with
      free eye screenings among adult residents of Hadrut and Martuni regions of
      Nagorno Karabakh (Artsakh) in 2014-2015. The study questionnaire included
      questions about sociodemographic characteristics, non-communicable diseases, use
      of eye care services, visual acuity, eye diseases, and VRQoL. National Eye
      Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) was used to assess
      VRQoL. In total, 531 adults participated in the study. RESULTS: The mean age of
      participants was 60.1 years (standard deviation [SD] = 13.7), ranging from 18 to
      90 years. The majority of participants were female (71.4%). The most frequently
      diagnosed eye disorder was cataract (33.8%). The prevalence of moderate and
      severe visual impairment was 7.0% and 0.8%, respectively. Almost 2.8% (15) of
      participants were blind. The mean global score of VFQ-25 in all study
      participants was 71.1 +/- 19.28 (SD), whereas the mean global scores of VFQ-25
      among not visually impaired, visually impaired, and blind participants were 74.0
      +/- 16.47 (SD), 51.7 +/- 21.77 (SD), and 30.9 +/- 20.2 (SD), respectively. In the
      adjusted linear regression model having moderate/severe visual impairment or
      blindness, age, socio-economic status, and having eye diseases such as glaucoma
      and cataract were significantly associated with VFQ-25 global score. The
      subscales of near vision, distance vision, peripheral vision, role difficulties,
      and mental health had significant associations with severe/moderate visual
      impairment in the adjusted analysis. After adjusting for visual impairment and
      demographic variables, participants with cataract and glaucoma were found to have
      statistically significant lower subscale scores than those without eye disease.
      CONCLUSION: Our data suggest that visual impairment was associated with lower
      scores of VRQoL. The strength of that association correlated with the increase in
      the level of visual impairment (from moderate/severe impairment to blindness).
      VRQoL was also shown to be affected by age, socio-economic status, and having eye
      diseases such as glaucoma and cataract. Further actions of remediation of visual
      impairment in this population are warranted.

PMID- 29049921
TI  - Estrus resynchronization in ewes with unknown pregnancy status.
AB  - Although fixed-time artificial insemination (FTAI) protocols are available for
      sheep, estrus resynchronization has not been previously reported. The objectives
      of this study were to evaluate the effect of estrus resynchronization with
      exogenous progestogen on endogenous progesterone levels and to compare pregnancy
      rates after two consecutive estrus synchronizations in ewes. In Experiment 1,
      ewes (n = 20) received an intravaginal device (IVD) containing 60 mg
      medroxyprogesterone acetate (MPA) for 10 days. At the IVD withdrawal (D0), ewes
      received 250 IU eCG and were allocated into two treatments: either no further
      treatment (Control; n = 10) or estrus resynchronization (Resynch; n = 10) from
      D12 to D19. Serum progesterone (P4) levels did not differ at D12 and D19 (P >
      0.05), but were greater at D15 for the Control compared with the Resynch group (P
      < 0.05). In experiment 2, ewes (n = 250) were submitted to a first
      synchronization protocol followed by estrus detection and either artificial
      insemination (AI) or natural mating (NM). Subsequently, ewes were divided into
      two groups: Control (n = 104): which received no further treatment and were bred
      by NM; and Resynch (n = 146): which were submitted to a second synchronization
      starting on D14 (first IVD withdrawal = D0) and to NM after second IVD withdrawal
      (D20). Cumulative pregnancy rates did not differ between the Control (67.3%,
      70/104) and Resynch (62.3%, 91/146) groups. In a third experiment, ewes (n = 83)
      were bred by two consecutive FTAI within a 20-day interval. Pregnancy rates after
      the first (30.1%, 25/83) and the second FTAI (36.2%, 21/58) did not differ (P >
      0.05). In conclusion, although exogenous progestogen supplementation reduced
      circulating levels of P4, pregnancy maintenance was unaffected. Estrus
      resynchronization in ewes is feasible, resulting in similar fertility after the
      first and the second services. The use of resynchronization coupled with
      artificial insemination using semen from genetically superior rams may
      potentially accelerate genetic improvement in sheep herds by allowing a higher
      differential selection compared with natural breeding.

PMID- 29049922
TI  - Effect of co-culture canine cumulus and oviduct cells with porcine oocytes during
      maturation and subsequent embryo development of parthenotes in vitro.
AB  - In the estrus stage, canine oocytes are surrounded by cumulus cells and undergo
      maturation in the oviduct for 2-3 days after ovulation. We hypothesized that
      canine oviduct cells (cOC) and canine cumulus cells (cCC) during this stage might
      affect the maturation of oocytes and thereby improve subsequent embryo
      development. Therefore, the objective of this study was to compare the effects of
      a cOC and cCC co-culture on oocyte in vitro maturation (IVM) and subsequent
      embryo development, and to analyze the gene expressions in a molecular fashion
      what co-culture actually gives the specific pathways in which the co-culture
      cells act to improve maturation and embryo development. The effect of co-culture
      using cOC and cCC on porcine oocyte IVM was investigated. Thereafter, oocytes
      were activated using electrical stimulation and embryo developmental competence
      was estimated. The expression of the genes related to oocyte maturation, embryo
      development and apoptosis were analyzed. Also, reactive oxygen species (ROS)
      levels after IVM was analyzed. The IVM rate and embryo development including
      cleavage, blastocyst formation rates, and total blastocyst cell numbers from cOC
      group were significantly higher than other groups (P < 0.05). The expression of
      SMAD2/3 and growth differentiation factor 9 (GDF9) was significantly increased in
      cOC and oocytes from the cOC group compared with other groups. Moreover, the
      levels of GDF9, prostaglandin-endoperoxide synthase 2 (PTGS2), WNT3A and matrix
      metalloproteinase 2 (MMP2) were significantly up-regulated in blastocysts from
      the cOC group. The concentration of ROS was significantly lower in the
      supernatant of cOC groups compared with other groups. Also, the expression of
      BCL2 was significantly increased in porcine cumulus cells and oocytes from cOC
      group. The present study demonstrated that co-culture with cOC improved in vitro
      porcine oocyte maturation and subsequent embryo development competence. Also, co
      culture with cOC during IVM induces a suitable environment for oocyte maturation
      by enhancing the mRNA level of SMAD2/3 and GDF9, and for embryo development by
      elevating the expression level of PTGS2, WNT3A and MMP2. In addition, the
      decreased ROS level in cOC co-culture could have a beneficial influence on oocyte
      maturation.

PMID- 29049923
TI  - Attenuation of heat stress-induced spermatogenesis complications by betaine in
      mice.
AB  - High temperatures can induce oxidative stress, impairment of spermatogenesis, and
      reduction of sperm quality and quantity concomitant with transient periods of
      partial or complete infertility in male mammals. Promising beneficial effects of
      betaine supplementation on the epididymal spermatozoa have been reported in
      experimental studies; however, its effects on testicular heat stress (HS)-induced
      impairment have yet to be determined. In the present study, betaine (Bet) was
      orally administrated (250 mg/kg day) during a 14-day period, before (Bet + HS
      group) or after (HS + Bet group) induction of testicular HS in 7-9 week-old male
      mice. HS was induced by testicular immersion in water at 42  degrees C in stress
      groups. Epididymal spermatozoa and testes were collected at days 14 and 28 after
      HS induction in order to analyze sperm characteristics, testicular oxidative
      status, and histological changes. Our studies showed that HS reduced testicular
      weight, the quality and quantity of epididymal spermatozoa, and impaired
      maturation of germinal cells. The levels of MDA, catalase, SOD, and GPX were
      increased in the testes of HS-induced mice (P < 0.01). Although betaine treatment
      before and after exposure to HS enhanced antioxidant defense (P < 0.05) and
      accelerated germinal epithelium regeneration, its effects on the characteristics
      of epididymal spermatozoa were scarce. On the other hand, in the absence of heat
      stress, quality and quantity of epididymal spermatozoa were improved following 14
      days of betaine consumption. Our study revealed the beneficial effect of betaine
      on HS-induced complications of spermatogenesis, as well as its potency to improve
      epididymal spermatozoa in intact mice.

PMID- 29049925
TI  - Omics tools: New challenges in aquatic nanotoxicology?
AB  - In recent years, the implication of genomics into ecotoxicological studies has
      been studied closely to allow a better understanding of organism's responses to
      environmental contaminants including engineering nanomaterials (ENMs). ENMs are
      increasingly produced for various applications including cosmetics, electronics,
      sports equipment, biomedicine and agriculture. Because of their small size, ENMs
      possess chemical or physical characteristics improved compared to the
      corresponding macro-sized material. As their application expend, the release of
      manufactured ENMs into the environment is likely to increase and concern over
      impacts for the aquatic ecosystem is growing. Several studies reported
      deleterious effect of ENMs to aquatic organisms, but there is little information
      about the molecular mechanisms of toxicity. The development of ecotoxicogenomic
      approaches will improve the characterization of cellular and molecular modes of
      action of ENMs to aquatic organisms and allow a better prediction of contaminants
      toxicity. This paper presents an overview of transciptomic/proteomic studies in
      freshwater and marine organisms exposed to ENMs. Overall, induction of gene
      expression in relations to defense mechanisms, immune responses, growth and
      reproduction were measured after ENMs exposures of organisms, but with different
      patterns depending on exposure duration and concentrations used. In addition,
      some studies reported a positive correlation between gene expression and cellular
      modifications, but not at the individual level.

PMID- 29049924
TI  - Equine mesenchymal stem cells derived from endometrial or adipose tissue share
      significant biological properties, but have distinctive pattern of surface
      markers and migration.
AB  - Adult stromal mesenchymal stem cells (MSCs) have been postulated as responsible
      for cell renewal in highly and continuously regenerative tissues such as the
      endometrium. MSCs have been identified in the endometrium of many species
      including humans, rodents, pets and some farm animals, but not in horses. The
      objective of this work was to isolate such cells from the endometrium of mares
      and to compare their main biological attributes with horse adipose-derived MSCs.
      Here we successfully isolated and characterized endometrial MSCs (eMSCs) from
      mares. Said cells showed fibroblast-like morphology, grew on plastic, had
      doubling population times of 46.4 +/- 3.38 h, underwent tri-lineage (osteo,
      chondro and adipogenic) differentiation after appropriate inductions, migrated
      toward the attraction of fetal calf serum and displayed a pattern of surface
      markers commonly accepted for horse MSCs. All these are properties of MSCs. Some
      of these attributes were shared with equine adipose-derived MSCs, but the
      migration pattern of eMSC at 12 and 24 h after stimulation was reduced in
      comparison with adipose MSCs. Also, expression of CD44, CD90 and MHCI surface
      markers were dramatically down-regulated in eMSCs. In conclusion, equine-derived
      endometrial MSC share biological attributes with adipose MSC of this species, but
      displayed a different surface marker phenotype and an impaired migration ability.
      Conceivably, this phenotype is distinctive for MSC of this origin.

PMID- 29049926
TI  - AFM-detected apoptosis of hepatocellular carcinoma cells induced by American
      ginseng root water extract.
AB  - American ginseng as a common and traditional herbal medicine has been used in
      cancer treatment for many years. However, the effect of American ginseng on the
      cancer cell response (i.e. apoptosis) has not been fully understood yet. Previous
      studies demonstrated that cellular apoptosis was associated with the changes of
      mechanical and morphological properties. Therefore, in this study, mechanical and
      morphological characterizations were carried out by both atomic force microscope
      (AFM) and inverted optical microscope to investigate the apoptosis of
      hepatocellular carcinoma (SMMC-7721) cells affected by American ginseng root
      water extract (AGRWE). The results showed that the cells treated with AGRWE
      exhibited significantly larger surface roughness, height and elastic modulus
      values than control group. Moreover, those parameters were upregulated under the
      higher concentration of AGRWE and longer culture time. Consequently, it indicates
      that the mechanical and morphological properties can be used as the apoptotic
      characteristics of SMMC-7721 cells. Also, the increased surface roughness and
      elastic modulus of cells under the AGRWE treatment have shown that the apoptosis
      of SMMC-7721 cells can be enhanced by AGRWE. This will provide an important
      implication for hepatocelluar carcinoma treatment and drug development.

PMID- 29049927
TI  - Electron tomography of whole cultured cells using novel transmission electron
      imaging technique.
AB  - Since a three-dimensional (3D) cellular ultrastructure is significant for
      biological functions, it has been investigated using various electron microscopic
      techniques. Although transmission electron microscopy (TEM)-based techniques are
      traditionally used, cells must be embedded in resin and sliced into ultrathin
      sections in sample preparation processes. Block-face observation using a scanning
      electron microscope (SEM) has also been recently applied to 3D observation of
      cellular components, but this is a destructive inspection and does not allow re
      examination. Therefore, we developed electron tomography using a transmission
      electron imaging technique called Plate-TEM. With Plate-TEM, the cells cultured
      directly on a scintillator plate are inserted into a conventional SEM equipped
      with a Plate-TEM observation system, and their internal structures are observed
      by detecting scintillation light produced by electrons passing through the cells.
      This technology has the following four advantages. First, the cells cultured on
      the plate can be observed at electron-microscopic resolution since they remain on
      the plate. Second, both surface and internal information can be obtained
      simultaneously by using electron- and photo-detectors, respectively, because a
      Plate-TEM detector is installed in an SEM. Third, the cells on the scintillator
      plate can also be inspected using light microscopy because the plate has
      transparent features. Finally, correlative observation with other techniques,
      such as conventional TEM, is possible after Plate-TEM observation because Plate
      TEM is a non-destructive analysis technique. We also designed a sample stage to
      tilt the samples for tomography with Plate-TEM, by which 3D organization of
      cellular structures can be visualized as a whole cell. In the present study, Mm2T
      cells were investigated using our tomography system, resulting in 3D
      visualization of cell organelles such as mitochondria, lipid droplets, and
      microvilli. Correlative observations with various imaging techniques were also
      conducted by successive observations with light microscopy, SEM, Plate-TEM, and
      conventional TEM. Consequently, the Plate-TEM tomography technique encourages
      understanding of cellular structures at high resolution, which can contribute to
      cellular biological research.

PMID- 29049928
TI  - Developmental changes in haemocyte morphology in response to Staphylococcus
      aureus and latex beads in the beetle Tenebrio molitor L.
AB  - The evolutionary success of insects is undoubtedly related to a well-functioning
      immune system. This is especially apparent during insect development by the
      adaptation of individuals to the changing risk of infection. In addition, current
      studies show that the insect immune system is characterized by some specificity
      in response to natural pathogens (for example, bacteria, viruses or fungi) and
      artificial challengers (for example, latex beads or nylon filaments). However,
      developmental changes and the specificity of immune system reactions
      simultaneously have not been analysed. Thus, the aim of the present research was
      to determine changes in haemocyte morphology in response to attenuated
      Staphylococcus aureus and latex beads across each developmental stage of the
      beetle Tenebrio molitor. The results of the present research clearly showed
      differences in the morphology of T. molitor haemocytes during development. The
      haemocytes of larvae and 4-day-old adult males were characterized by the highest
      adhesion ability, which was expressed as the largest average surface area,
      filopodia length and number of filopodia. In contrast, the haemocytes of pupae
      and 30-day-old adult males had a significantly lower value for these
      morphological parameters, which was probably related to metamorphosis (pupae) and
      immunosenescence (30-day-old adults). The haemocytes of the tested individuals
      reacted differently to the presence of S. aureus and latex beads. The presence of
      S. aureus led to a significant decrease in all previously mentioned morphological
      parameters in larvae and in both groups of adult individuals. In these groups,
      incubation of haemocytes with latex beads caused only a slight decrease in
      surface area and filopodia length and number. This morphological response of
      haemocytes to biotic and artificial challengers might be related to an increase
      in the migration abilities of haemocytes during infection. However, the
      differences in haemocyte reactivity towards S. aureus and latex beads might be
      explained by differences in pathogen recognition. Conversely, increased adhesive
      abilities of pupal haemocytes were also observed, which might be related to the
      specificity of metamorphosis and the hormonal titre during this developmental
      stage.

PMID- 29049929
TI  - Aggression, emotional self-regulation, attentional bias, and cognitive inhibition
      predict risky driving behavior.
AB  - The present study explored whether aggression, emotional regulation, cognitive
      inhibition, and attentional bias towards emotional stimuli were related to risky
      driving behavior (driving errors, and driving violations). A total of 117
      applicants for taxi driver positions (89% male, M age=36.59years, SD=9.39, age
      range 24-62years) participated in the study. Measures included the Ahwaz
      Aggression Inventory, the Difficulties in emotion regulation Questionnaire, the
      emotional Stroop task, the Go/No-go task, and the Driving Behavior Questionnaire.
      Correlation and regression analyses showed that aggression and emotional
      regulation predicted risky driving behavior. Difficulties in emotion regulation,
      the obstinacy and revengeful component of aggression, attentional bias toward
      emotional stimuli, and cognitive inhibition predicted driving errors. Aggression
      was the only significant predictive factor for driving violations. In conclusion,
      aggression and difficulties in regulating emotions may exacerbate risky driving
      behaviors. Deficits in cognitive inhibition and attentional bias toward negative
      emotional stimuli can increase driving errors. Predisposition to aggression has
      strong effect on making one vulnerable to violation of traffic rules and crashes.

PMID- 29049931
TI  - Effectiveness of General Practitioner training to improve suicide awareness and
      knowledge and skills towards depression.
AB  - BACKGROUND: General Practitioners (GPs) are well placed as gatekeepers for
      managing depression and suicidal ideation but not always well prepared. Capacity
      building has therefore been recommended as a useful strategy for suicide
      prevention. This study aimed to examine whether GPs' knowledge and attitudes
      towards and confidence to deal with depression and suicide improve after
      following a training program. METHODS: As part of the OSPI-Europe multilevel
      intervention, a standardized training on depression and suicide was provided to
      208 GPs in three European countries. Core outcomes were assessed using the
      Depression Attitude Questionnaire, the Attitude towards Suicide Prevention Scale,
      and the Morriss Confidence Scale. Data were collected before and after training,
      and at three to six months follow-up. RESULTS: At baseline, GPs demonstrated
      various stigmatizing attitudes towards depression and low optimism about the
      therapeutic treatment of depression. They showed moderately positive attitudes
      towards suicide prevention but felt little confident in dealing with depression
      and suicide in daily practice. The training resulted in improved knowledge,
      attitudes and confidence regarding depression and suicide and their prevention
      and treatment. At follow-up, only the increase in confidence to deal with
      depression and suicide was sustained. LIMITATIONS: The Depression Attitude
      Questionnaire has rather weak psychometric properties. Other external factors may
      have contributed to the observed training effects as the study included no
      control group. CONCLUSIONS: The OSPI-Europe training program was able to improve
      the GPs' attitudes towards suicide prevention, several attitudes towards
      depression and its treatment as well as the GPs' confidence to deal with
      depression and suicide in everyday practice. At follow, only the GPs' confidence
      to deal with depression and suicide was preserved.

PMID- 29049930
TI  - Antibiotic efficacy-context matters.
AB  - Antibiotic lethality is a complex physiological process, sensitive to external
      cues. Recent advances using systems approaches have revealed how events
      downstream of primary target inhibition actively participate in antibiotic death
      processes. In particular, altered metabolism, translational stress and DNA damage
      each contribute to antibiotic-induced cell death. Moreover, environmental factors
      such as oxygen availability, extracellular metabolites, population heterogeneity
      and multidrug contexts alter antibiotic efficacy by impacting bacterial
      metabolism and stress responses. Here we review recent studies on antibiotic
      efficacy and highlight insights gained on the involvement of cellular
      respiration, redox stress and altered metabolism in antibiotic lethality. We
      discuss the complexity found in natural environments and highlight knowledge gaps
      in antibiotic lethality that may be addressed using systems approaches.

PMID- 29049932
TI  - Determinants of comorbid depression and anxiety postnatally: A longitudinal
      cohort study of Chinese-Canadian women.
AB  - BACKGROUND: Women with comorbid depression and anxiety in the postpartum period
      experience more complex and severe symptoms than women with depression or anxiety
      alone; however, little is known about what influences these symptoms, especially
      among women from specific ethnic backgrounds. The objective of this study was to
      identify determinants of comorbid depression and anxiety symptomatology by 24
      weeks postpartum in a cohort of Chinese-Canadian women. METHODS: A longitudinal
      cohort study was completed where 549 Chinese immigrant and Canadian-born women in
      Toronto were followed to 24 weeks postpartum. Questionnaires included risk
      factors measured at 4 weeks. Logistic regression was used to develop a model of
      comorbidity (Edinburgh Postnatal Depression Scale score > 9; State-Trait Anxiety
      Inventory score > 40) up to and including 24 weeks. RESULTS: Previous history of
      postpartum (AOR 2.42, 95% CI 1.42-4.14) and non-postpartum (AOR 4.20, 95% CI 2.21
      7.98) depression, maternal age < 26 years (AOR 1.83, 95% CI 1.04-3.22),
      perception of support (AOR 0.97, 95% CI 0.94-1.00), acculturative stress (AOR
      1.03, 95% CI 1.01-1.04), maternal fatigue (AOR 1.12, 95% CI 1.07-1.17), and
      perceived infant sleep problems (AOR 2.06, 95% CI 1.27-3.43) were significantly
      associated with comorbid depression and anxiety in the first 24 weeks postpartum.
      LIMITATIONS: Our sample consisted of Chinese-Canadian women; this study should be
      replicated in other ethnic groups to see if and how risk factors of postpartum
      comorbidity differ. CONCLUSION: The factors identified herein offer insight into
      groups of Chinese-Canadian women who might benefit most from early identification
      and treatment and suggest targets for prevention.

PMID- 29049933
TI  - Systemic autoimmune diseases are associated with an increased risk of bipolar
      disorder: A nationwide population-based cohort study.
AB  - BACKGROUND: Studies suggested autoimmunity plays a role in the etiology of
      bipolar disorder (BD). This study aimed to investigate the association between
      systemic autoimmune diseases (SADs) and the subsequent development of BD, and
      examine the potential risk factors for developing BD. METHODS: Patients with SADs
      were identified in the Taiwan National Health Insurance Program (NHIP). A
      comparison cohort was created by matching patients without SADs with age. The
      SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992
      patients. The incidence of BD was evaluated in both cohorts. RESULTS: The major
      finding was the discovery of a higher incidence of subsequent BD among patients
      with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was
      observed to be significant increase in systemic lupus erythematosus, rheumatoid
      arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease.
      Furthermore, our study revealed some potential risk factors for developing BD
      including female, younger age and patients who lived in eastern Taiwan. Also,
      some comorbidities including dyslipidemia, chronic obstructive pulmonary disease,
      diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver
      cirrhosis, and malignancies were potential risk factors for incident BD.
      LIMITATIONS: The diagnosis of SADs was based on the catastrophic illness
      certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored
      for subsequent developing BD. CONCLUSION: This study confirms that SADs are
      associated with higher incidence of BD, suggesting that abnormal autoimmune
      process is associated with increased expression of psychiatric disturbances.

PMID- 29049934
TI  - Molecular changes associated with escitalopram response in a stress-based model
      of depression.
AB  - Converging evidence points at hypothalamus-pituitary-adrenal (HPA) axis
      hyperactivity and neuroinflammation as important factors involved in the
      etiopathogenesis of major depressive disorder (MDD) and in therapeutic efficacy
      of antidepressants. In this study, we examined the molecular effects associated
      with a response to a week-long treatment with escitalopram in the chronic escape
      deficit (CED) model, a validated model of depression based on the induction of an
      escape deficit after exposure of rats to an unavoidable stress. We confirmed our
      previous result that a treatment with escitalopram (10mg/kg) was effective after
      7days in reverting the stress-induced escape deficit in approximately 50% of the
      animals, separating responders from non-responders. Expression of markers of HPA
      axis functionality as well as several inflammatory mediators were evaluated in
      the hypothalamus, a key structure integrating signals from the neuro, immune,
      endocrine systems. In the hypothalamus of responder animals we observed a
      decrease in the expression of CRH and its receptors and an increase in GR protein
      in total and nuclear extracts; this effect was accompanied by a significant
      decrease in circulating corticosterone in the same cohort. Hypothalamic IL-1beta
      and TNFalpha expression were increased in stressed animals, while CXCL2, IL-6,
      and ADAM17 mRNA levels were decreased in escitalopram treated rats regardless of
      the treatment response. These data suggest that efficacy of a one week treatment
      with escitalopram may be partially mediated by a decrease HPA axis activity,
      while in the hypothalamus the drug-induced effects on the expression of immune
      modulators did not correlate with the behavioural outcome.

PMID- 29049935
TI  - Intranasal oxytocin in the treatment of anorexia nervosa: Randomized controlled
      trial during re-feeding.
AB  - BACKGROUND: Nutritional rehabilitation in anorexia nervosa (AN) is impeded by
      fear of food, eating and change leading to treatment resistance. Oxytocin (OT)
      exerts prosocial effects and modulates trust, fear, anxiety and neuroplasticity.
      The current placebo-controlled RCT examined the effects of intranasal oxytocin
      (IN-OT) in AN. The aim was to ascertain whether repeated doses of IN-OT enhance
      treatment outcomes in AN. METHODS: AN patients self-administered 36 IU IN-OT or
      placebo daily for 4-6 weeks during hospital treatment. The outcome measures were
      change in the Eating Disorders Examination (EDE) scale, weight gain, cognitive
      rigidity, social anxiety, obsessive and autistic symptoms. The effects of the
      first and last doses of IN-OT were assessed relative to placebo before and after
      a high-energy afternoon snack, to determine potential dampening of cortisol and
      anxiety levels by OT. RESULTS: Weight gain was similar in both groups. The EDE
      eating concern subscale score was significantly lower after IN-OT treatment as
      was cognitive rigidity. There were no significant differences in social anxiety
      or any of the other outcomes at follow-up. After four weeks IN-OT, salivary
      cortisol levels were significantly lowered in anticipation of an afternoon snack
      compared to placebo. Morning plasma OT levels did not change after chronic IN-OT
      or with weight restoration. CONCLUSION: IN-OT might enhance nutritional
      rehabilitation in AN by reducing eating concern and cognitive rigidity. Lower
      salivary cortisol levels in response to IN-OT suggest diminished neuroendocrine
      stress responsiveness to food and eating. Such effects require replication with
      inclusion of more sensitive subjective measures.

PMID- 29049936
TI  - Memorable objects are more susceptible to forgetting: Evidence for the inhibitory
      account of retrieval-induced forgetting.
AB  - Retrieval of target information can cause forgetting for related, but non
      retrieved, information - retrieval-induced forgetting (RIF). The aim of the
      current studies was to examine a key prediction of the inhibitory account of RIF 
      interference dependence - whereby 'strong' non-retrieved items are more likely
      to interfere during retrieval and therefore, are more susceptible to RIF. Using
      visual objects allowed us to examine and contrast one index of item strength 
      object typicality, that is, how typical of its category an object is. Experiment
      1 provided proof of concept for our variant of the recognition practice paradigm.
      Experiment 2 tested the prediction of the inhibitory account that the magnitude
      of RIF for natural visual objects would be dependent on item strength. Non
      typical objects were more memorable overall than typical objects. We found that
      object memorability (as determined by typicality) influenced RIF with significant
      forgetting occurring for the memorable (non-typical), but not non-memorable
      (typical), objects. The current findings strongly support an inhibitory account
      of retrieval-induced forgetting.

PMID- 29049938
TI  - Dietary patterns in french home-living older adults: Results from the PRAUSE
      study.
AB  - The aim of the present study was to provide descriptive dietary patterns of home
      living older adults, and to examine their association with sociodemographic and
      'diet-related' variables, and health and psychological factors. Dietary patterns
      were analyzed using separately cluster analysis for men (N=151,Mage=72.72,
      SD=8.80, range=56-97) and women (N=251, Mage=76.74, SD=9.95, range=55-97) in 402
      older adults aged 55 years and over. Cluster analyses showed four distinct
      dietary profiles for each gender. In older men, the four distinct dietary
      clusters were associated with any differences in sociodemographic and 'diet
      related' variables, cognitive function, and health and psychological factors.
      Likewise, in older women, the four distinct dietary clusters were associated with
      any differences in sociodemographic and 'diet-related' variables'. However in
      older women, results showed that the cluster 1 "high fish-fruit-vegetable" was
      associated with a better cognitive function, a better self-rated health and no
      depressive symptoms, whereas cluster 3 "moderate ready meals" was associated with
      cognitive decline, slight depression, and poor perceived health. Results
      emphasize the interest to take into consideration health and psychological
      factors associated with dietary patterns to better target the vulnerability of
      individuals and enable an effective prevention.

PMID- 29049937
TI  - Risk of cardiovascular disease among women with endometrial cancer compared to
      cancer-free women in the Women's Health Initiative.
AB  - BACKGROUND: The majority of women diagnosed with endometrial cancer (EC) have low
      cancer-specific mortality; however, a high prevalence of cardiovascular disease
      (CVD) risk factors places EC patients at high risk of developing CVD. In the
      Women's Health Initiative (WHI), we assessed the hypothesis that CVD risk was
      higher among women who developed EC compared with women who did not develop EC.
      METHODS: We compared the incidence of fatal and non-fatal CVD events among 1,179
      women who developed Type I EC, 211 women who developed Type II EC, and 92,217
      women who did not develop EC. We first estimated univariable cause-specific
      hazard ratios (CHRs) and 95% confidence intervals (CIs) for the association
      between an EC diagnosis (overall and by EC type) with CVD risk using Cox
      proportional hazards regression. Potential confounders were examined using a risk
      factor modeling approach; final multivariable-adjusted models included covariates
      that changed univariable CHRs for EC diagnosis by>=5%. RESULTS: In multivariable
      adjusted models, CVD risk did not significantly differ between women who
      developed EC compared to women who did not develop EC (CHR=1.01, 95% CI=0.87
      1.16), particularly for the subgroup of women who developed Type I EC (CHR=0.98,
      95% CI=0.84-1.14); however, there was a positive but statistically nonsignificant
      association for Type II EC (CHR=1.32, 95% CI=0.88-1.97). CONCLUSION: Despite our
      null findings, women with EC should still receive counseling and support to make
      lifestyle changes aimed at reducing weight as appropriate, given the high
      prevalence of CVD risk factors at diagnosis.

PMID- 29049939
TI  - Water assessment using ultra-weak bioluminescence.
AB  - In this paper a method to evaluate the presence of microorganisms of the coliform
      group in water samples using the ultra-weak bioluminescence (UWB) is proposed. A
      series of UWB measurements and optical density measurements from cultures of both
      a set of standard E. coli strain samples, and a set of water samples from a river
      near Curitiba City in Brazil were performed. All samples were previously
      incubated at 37 degrees C for 11h in nutritive medium before the temporal UWB
      emission profiles data were acquired for a period of 24h inside a dark chamber of
      an especially implemented instrumentation capable of doing photon counting
      measurements. For the optical density measurements, a spectrophotometer was used
      to acquire the growth kinetics of those cultures for a period of 13h, and the
      results compared to the UWB profiles. Periodic time-components analysis of the
      UWB data from both the set of standard E. coli samples and the set of the river's
      water samples were performed and compared to each other. The results have shown
      that the UWB temporal profiles resemble in some way the growth kinetics curve and
      the periodic time-components analysis is an effective way to discriminate between
      contaminated and non-contaminated samples, therefore the method may be viable for
      detecting coliforms in water samples in less time than usual methods.

PMID- 29049940
TI  - Photocatalytic degradation of synthetic food dye, sunset yellow FCF (FD&C yellow
      no. 6) by Ailanthus excelsa Roxb. possessing antioxidant and cytotoxic activity.
AB  - The purpose of our work is to identify the bioactive compounds of bark and leaves
      extract from Ailanthus excelsa Roxb. and to explore its effectiveness against
      synthetic food dye. The presence of primary and secondary metabolites was
      confirmed by carrying out phytochemicals analysis. With the prior knowledge
      accessible on the indispensable secondary metabolites holding antioxidant and
      cytotoxicity activity, the quantitative screening of total phenolic and flavonoid
      content in methanolic and aqueous extract of bark and leaves from Ailanthus
      excelsa were done. Comparatively, a higher value of flavonoid (161+/-0.3MUg/mg)
      and phenolic acid content (152.4+/-0.14MUg/mg) was found in bark extract. By FTIR
      analysis, the characteristic peak was obtained at 1581.63 and 1598.99cm-1
      confirmed the presence of functional groups associated to flavonoids and other
      phenolic groups respectively. In bark extract, 81% of DPPH inhibition was
      observed when compared to ascorbic acid (standard) 92% of free radical scavenging
      activity. Bark extract from Ailanthus excelsa exhibited 71% cytotoxicity against
      HeLa cell line (cervical cancer). In examining the toxicity level of crude
      extracts with red blood cells (RBC), the bark extract was showed a very less
      (2.8%) haemolytic activity. They also showed maximum zone of inhibition in
      antibacterial activity i.e. 13+/-0.5mm against Escherichia coli culture. At a
      concentration of 10mg/mL of crude extract from A. excelsa, 55% degradation of
      sunset yellow dye was observed. It concludes that, the compounds present in the
      A. excelsa, especially the bark extract showed better photocatalytic, haemolytic,
      antioxidant, cytotoxicity and antibacterial activity when compared to leaves
      extract.

PMID- 29049941
TI  - Induced structural changes of humic acid by exposure of polystyrene
      microplastics: A spectroscopic insight.
AB  - The occurrence of microplastics (MPs) as emerging contaminants in the environment
      may cause changes in water or sediment characteristics, and further affect their
      biogeochemical cycles. Thus, insights into the interactions between dissolved
      organic matter (DOM) and MPs are essential for the assessment of environmental
      impacts of MPs in ecosystems. Integrating spectroscopic methods with chemometric
      analyses, this work explored the chemical and microstructural changes of DOM-MP
      complex to reveal the mechanism of DOM-MP interaction at a molecular level. MPs
      were found to interact with the aromatic structure of DOM via pi-pi conjugation,
      then be entrapped in the DOM polymers by the carboxyl groups and C=O bonds,
      constituting a highly conjugated co-polymer with increased electron density. This
      induced the fluorescence intensity increase in DOM. The interaction affinity of
      DOM-MP was highly dependent on the MP size and solution pH. This work offers a
      new insight into the impact of MP discharge on environment and may provide an
      analytical framework for evaluating MP hetero-aggregation and the roles of MPs in
      the transportation of other contaminants. Furthermore, the integrated methods
      used in this work exhibit potential applications in exploring the fragmentation
      processes of MPs and formation of secondary MPs under natural conditions.

PMID- 29049942
TI  - Bioaugmentation of thiabendazole-contaminated soils from a wastewater disposal
      site: Factors driving the efficacy of this strategy and the diversity of the
      indigenous soil bacterial community.
AB  - The application of the fungicide thiabendazole (TBZ) in fruit packaging plants
      (FPP) results in the production of effluents which are often disposed in adjacent
      field sites. These require remediation to prevent further environmental dispersal
      of TBZ. We assessed the bioaugmentation potential of a newly isolated TBZ
      degrading bacterial consortium in a naturally contaminated soil (NCS) exhibiting
      a natural gradient of TBZ levels (12000, 400, 250 and 12 mg kg-1). The effect of
      aging on bioaugmentation efficacy was comparatively tested in a soil with similar
      physicochemical properties and soil microbiota, which was artificially,
      contaminated with the same TBZ levels (ACS). The impact of bioaugmentation and
      TBZ on the bacterial diversity in the NCS was explored via amplicon sequencing.
      Bioaugmentation effectively removed TBZ from both soils at levels up to 400 mg kg
      1 but failed at the highest contamination level (12000 mg kg-1). Dissipation of
      TBZ in bioaugmented samples showed a concentration-dependent pattern, while aging
      of TBZ had a slight effect on bioaugmentation efficiency. Bioaugmentation had no
      impact on the soil bacterial diversity, in contrast to TBZ contamination. Soils
      from the hotspots of TBZ contamination (12000 mg kg-1) showed a drastically lower
      alpha-diversity driven by the dominance of beta- and gamma-proteobacteria at the
      expense of all other bacterial phyla, especially Actinobacteria. Overall,
      bioaugmentation with specialized microbial inocula could be an effective solution
      for the recovery of disposal sites contaminated with persistent chemicals like
      TBZ.

PMID- 29049943
TI  - Occurrence and profile of organophosphorus compounds in fine and coarse
      particulate matter from two urban areas of China and Pakistan.
AB  - Seven organophosphorus compounds (OPs) were measured in urban fine and coarse
      particulate matter (PM) collected from two sites of Nanjing (XCNUC), China and
      Islamabad (APHSP), Pakistan. The fine PM mass at APHSP site was significantly
      higher (p = 0.005) in the spring (mean 22.5 MUg/m3) than in the summer (mean 12.7
      MUg/m3). The total concentration, ?7OPs, of samples collected at APHSP was found
      significantly higher in coarse (range 672-47621 pg/m3) than in fine PM (range
      1200-15213 pg/m3); while ?7OPs from XCNUC in fine (range 1696-15063 pg/m3) and
      coarse PM (range 2053-5379 pg/m3) were statistically different in samples during
      summer, based on two-sample t-test at 0.05 confidence interval. Seasonally, ?7OPs
      was found to be higher in the samples of Nanjing (9510 +/- 3633 pg/m3) in the
      summer than in the spring. In contrast, the samples of Islamabad had higher ?7OPs
      (25558 +/- 16255 pg/m3) in the spring than in the summer. Tri(chloropropyl)
      phosphate (TCEP) was found at higher concentration than any other OPs in the
      samples from the XCNUC site. Triphenyl phosphate (TPhP) was found at extremely
      high levels from APHSP, which may attributed to its use in jet fuel. Most of the
      ?OPs concentrations were found significantly different in both PMs at both sites
      due to their diverse sources. Both sites showed strong correlation of ?OPs with
      TCEP in both PMs, indicating similar mode of transfer from sources like plastics,
      lacquer, paint, glue, industrial processes and foam fillers. Relative abundance
      of OPs in fine and coarse PM differs amongst OP congeners and concerning seasons,
      with these variations attributed to different mechanisms of mass transfer such as
      volatilization, condensation and abrasions. Moreover, triphenylphosphine oxide
      (TPPO) has been reported in outdoor PMs. This is the first study on the
      occurrence of OPs in atmospheric fine and coarse PM and their seasonal variation
      from Pakistan and China.

PMID- 29049944
TI  - Bioaccumulation and effects of novel chlorinated polyfluorinated ether sulfonate
      in freshwater alga Scenedesmus obliquus.
AB  - Chlorinated polyfluorinated ether sulfonate (Cl-PFESA) is a novel alternative
      compound for perfluorooctane sulfonate (PFOS), with its environmental risk not
      well known. The bioaccumulation and toxic effects of Cl-PFESA in the freshwater
      alga is crucial for the understanding of its potential hazards to the aquatic
      environment. Scenedesmus obliquus was exposed to Cl-PFESA at ng L-1 to mg L-1,
      with the exposure regime beginning at the environmentally relevant level. The
      total log BAF of Cl-PFESA in S. obliquus was 4.66, higher than the reported log
      BAF of PFOS in the freshwater plankton (2.2-3.2). Cl-PFESA adsorbed to the cell
      surface accounted for 33.5-68.3% of the total concentrations. The IC50 of Cl
      PFESA to algal growth was estimated to be 40.3 mg L-1. Significant changes in
      algal growth rate and chlorophyll a/b contents were observed at 11.6 mg L-1 and
      13.4 mg L-1 of Cl-PFESA, respectively. The sample cell membrane permeability,
      measured by the fluorescein diacetate hydrolyzation, was increased by Cl-PFESA at
      5.42 mg L-1. The mitochondrial membrane potential, measured by Rh123 staining,
      was also increased, indicating the hyperpolarization induced by Cl-PFESA. The
      increasing ROS and MDA contents, along with the enhanced SOD, CAT activity, and
      GSH contents, suggested that Cl-PFESA caused oxidative damage in the algal cells.
      It is less possible that current Cl-PFESA pollution in surface water posed
      obvious toxic effects on the green algae. However, the bioaccumulation of Cl
      PFESA in algae would contribute to its biomagnification in the aquatic food chain
      and its effects on membrane property could potentially increase the accessibility
      and toxicity of other coexisting pollutants.

PMID- 29049945
TI  - The Ages and Stages Questionnaire: Latent factor structure and growth of latent
      mean scores over time.
AB  - BACKGROUND: Very little research exists that looks at the Ages and Stages
      Questionnaire simultaneously from a modern latent variable point of view and by
      looking at its psychometric properties over time. AIMS: To explore the latent
      factor structure of the ASQ using Exploratory Structural Equation Modeling
      techniques for ordinal data and investigate its change over time using the method
      of vertical scaling from multidimensional Item Response Theory. STUDY DESIGN:
      Longitudinal, with the same children being assessed at multiple timepoints.
      SUBJECTS: Children measured using the 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36,
      42, 48month questionnaires of the ASQ. Initial sample (12months) consisted of
      2219 children and final sample (48months), 892 children due to drop-out. OUTCOME
      MEASURES: Ages and Stages Questionnaire, 3rd version (ASQ-3). RESULTS: Results
      indicate that all ASQ-3 age questionnaires examined showed the proposed 5-factor
      structure (except the 12-month version) but with different patterns over time.
      The Gross Motor domain had the fewest misfitting items, from 12months onwards.
      The Personal-Social domain and the Problem Solving domain had larger numbers of
      misfitting items. Results from the vertical scaling analysis showed that both the
      Problem-Solving and Personal-Social dimensions also exhibited the most complex
      patterns of change over time. CONCLUSIONS: The psychometric properties of the ASQ
      3 seem to be both time-dependent and domain-dependent. Earlier questionnaires
      reflect a latent structure that was not as well-defined as for later versions.
      Also, domains such as Communication and Gross Motor appear to be much more
      reliably measured than others, such as Problem-Solving and Personal-Social.

PMID- 29049946
TI  - Rechargeable, flexible and mediator-free biosupercapacitor based on transparent
      ITO nanoparticle modified electrodes acting in uM glucose containing buffers.
AB  - We present a transparent and flexible self-charging biosupercapacitor based on an
      optimised mediator- and membrane-free enzymatic glucose/oxygen biofuel cell.
      Indium tin oxide (ITO) nanoparticles were spray-coated on transparent conducting
      ITO supports resulting in a flocculent, porous and nanostructured electrode
      surface. By this, high capacitive currents caused by an increased electrochemical
      double layer as well as enhanced catalytic currents due to a higher number of
      immobilised enzyme molecules were obtained. After a chemical pre-treatment with a
      silane derivative, bilirubin oxidase from Myrothecium verrucaria was immobilized
      onto the ITO nanostructured electrode surface under formation of a biocathode,
      while bioanodes were obtained by either immobilisation of cellobiose
      dehydrogenase from Corynascus thermophilus or soluble PQQ-dependent glucose
      dehydrogenase from Acinetobacter calcoaceticus. The latter showed a lower
      apparent KM value for glucose conversion and higher catalytic currents at uM
      glucose concentrations. Applying the optimised device as a biosupercapacitor in a
      discontinuous charge/discharge mode led to a generated power output of
      0.030mW/cm2 at 50uM glucose, simulating the glucose concentration in human tears.
      This represents an enhancement by a factor of 350 compared to the power density
      obtained from the continuously operating biofuel cell with a maximum power output
      of 0.086uW/cm2 under the same conditions. After 17h of charging/discharging
      cycles a remarkable current enhancement was still measured. The entire device was
      transferred to flexible materials and applied for powering a flexible display
      showing its potential applicability as an intermittent power source in smart
      contact lenses.

PMID- 29049947
TI  - 3D spongy graphene-modified screen-printed sensors for the voltammetric
      determination of the narcotic drug codeine.
AB  - Adenine-functionalized spongy graphene (FSG) composite, fabricated via a facile
      and green synthetic method, has been explored as a potential electrocatalyst
      toward the electroanalytical sensing of codeine phosphate (COD). The synthesized
      composite is characterized using Fourier transform infrared spectroscopy (FTIR),
      Raman spectroscopy, X-ray powder diffraction, UV-vis absorption spectroscopy,
      scanning electron microscopy, high resolution transmission electron microscopy
      (HRTEM), and thermogravimetric analysis. The FSG was electrically wired via
      modification upon screen-printed (macro electrode) sensors, which behave as a
      hybrid electrode material for the sensitive and selective codeine phosphate (COD)
      determination in the presence of paracetamol (PAR) and caffeine (CAF). The FSG-
      modified sensor showed an excellent electrocatalytic response towards the sensing
      of COD with a wide linear response range of 2.0 * 10-8-2.0 * 10-4M and a
      detection limit (LOD) of 5.8 * 10-9M, indicating its potential for the sensing of
      COD in clinical samples and pharmaceutical formulations.

PMID- 29049948
TI  - Altered responsiveness in psychogenic nonepileptic seizures and its implication
      to underlying psychopathology.
AB  - PURPOSE: Altered responsiveness during psychogenic nonepileptic seizures (PNES)
      is a distinct semiological feature that may signal a psychological vulnerability.
      We hypothesized that altered responsiveness is related to difficulties with
      emotion tolerance, experiential avoidance, difficulty coping, dissociation and
      trauma and prior experiences of loss of awareness. METHODS: 71 patients with
      video-EEG confirmed PNES were divided into two groups based on their
      responsiveness at the time of the captured event during long-term monitoring.
      Demographic information, clinical history and self-rated questionnaires
      highlighting psychopathology were compared between the groups. RESULTS: 47
      patients (66%) had altered responsiveness during their captured event. Married or
      partnered subjects were more represented in the altered responsiveness group.
      Experiential avoidance, as measured by the Acceptance and Action Questionnaire
      II, and affect intolerance, as measured by the Affective Style Questionnaire,
      were significantly higher in the altered responsiveness group. The Connor
      Davidson Resilience Scale was significantly higher among intact responsiveness
      subjects. Subjects with altered responsiveness were more likely to have a family
      history of seizures, comorbid headaches, and loss of consciousness (LOC) during
      traumatic brain injury. There were no differences in measures of dissociation,
      somatization, mood or anxiety, or presence of psychiatric comorbidities,
      including PTSD or history of trauma. CONCLUSION: Altered responsiveness during
      PNES is a marker of lower emotional resilience or ability to tolerate emotions
      among patients with PNES. Emotion management may be an important therapeutic
      target for these patients. Prior experiences with LOC also contribute to the
      presence of altered responsiveness. Trauma and dissociation did not differentiate
      responsiveness during PNES.

PMID- 29049949
TI  - Rhinovirus viremia in adult patients with high viral load in bronchoalveolar
      lavages.
AB  - BACKGROUND: In children, rhinovirus viremia has been associated with higher
      nasopharyngeal loads and increase in severity of clinical signs and symptoms.
      OBJECTIVES: This study aims to detect rhinovirus viremia in adult patients and to
      establish potential correlations with the clinical course. STUDY DESIGN: Adult
      patients with rhinovirus strongly positive bronchoalveolar lavages (BAL,
      quantitation cycle, Cq values <25) detected between 2008 and 2014 were studied
      retrospectively. Blood sampled between two weeks before and two weeks after BAL
      sampling was tested for rhinovirus RNA. Underlying conditions, symptoms,
      radiography, microbiological data, and disease outcome were analysed. RESULTS:
      Twenty-seven of 43 patients with rhinovirus positive BAL at Cq values <25 had
      blood samples available within the prespecified time-frame (mean blood 3-4
      samples per patient). Four of these 27 patients (15%) tested rhinovirus RNA
      positive in their blood (of whom one patient twice). Genotyping demonstrated
      rhinovirus A01, A24, B52 and B92 in these four immunocompromised patients.
      Viremic patients were not significantly different with regard to underlying
      conditions, respiratory symptoms, radiological findings, co-pathogens nor the
      number of blood samples tested for RV. However, patients with rhinovirus viremia
      had significant higher mortality rates compared to patients without viremia, as
      all four died as a consequence of respiratory problems (100%) versus 22% (5/23),
      p=0.007 (Fisher's exact). CONCLUSIONS: Rhinovirus viremia can occur in adult
      patients with a high viral load in BAL fluid. Rhinovirus viremia may be
      considered a negative prognostic factor, although a causative role with regard to
      the adverse outcome has yet to be demonstrated.

PMID- 29049950
TI  - Understanding arithmetic concepts: Does operation matter?
AB  - Most research on children's arithmetic concepts is based on (a) additive concepts
      and (b) a single concept leading to possible limitations in current understanding
      about how children's knowledge of arithmetic concepts develops. In this study,
      both additive and multiplicative versions of six arithmetic concepts (identity,
      negation, commutativity, equivalence, inversion, and associativity) were
      investigated in Grades 5, 6, and 7. The multiplicative versions of the concepts
      were more weakly understood. No grade-related differences were found in
      conceptual knowledge, but older children were more accurate problem solvers.
      Individual differences were examined through cluster analyses. All children had a
      solid understanding of identity and negation. Some children had a strong
      understanding of all the concepts, both additive and multiplicative; some had a
      good understanding of equivalence or commutativity; and others had a weak
      understanding of commutativity, equivalence, inversion, and associativity.
      Associativity was the most difficult concept for all clusters. Grade did not
      predict cluster membership. Overall, these results demonstrate the breadth of
      individual variability in conceptual knowledge of arithmetic as well as the
      complexity in how children's understanding of arithmetic concepts develops.

PMID- 29049951
TI  - The mechanics of dental occlusion and disclusion.
AB  - BACKGROUND: The mechanical environment associated with occluding teeth is the
      foundation for a wide range of research topics, clinical practice and dogma,
      product development and marketing, and medico-legal issues. The purpose of this
      study was to experimentally examine the relationships between occlusal factors
      and their impact on the associated contact forces. METHODS: Matching pairs of 0
      degrees , 20 degrees , 33 degrees  and 40 degrees  cusp first molar denture teeth
      were placed into Class I, II and III molar relationships. As the teeth were
      brought together into occlusion and then separated, the loads experienced by the
      mandibular tooth were continuously measured by a load cell that was supporting
      it. FINDINGS: Loess smoothing splines were fitted to all data curves to calculate
      95% confidence intervals. All lateral force magnitudes and directions were
      statistically different when compared between classes of occlusion, cusp angles,
      and occlusion vs. disclusion. Noteworthy counterintuitive observations were that
      the lateral contact force components were generally higher during disclusion than
      occlusion, the peak lateral force magnitudes did not always occur when the
      occlusal force was maximum, and the lateral contact force component magnitude can
      be larger than the occlusal force. INTERPRETATION: Wedging and friction account
      for these unexpected results. The data indicate that each occlusion/disclusion
      cycle is characterized by complex transient loads that may impact wear facet and
      non-carious cervical lesion formation, implant and restorative failures, various
      aspects of occlusal trauma, and the concept of axial occlusal loading.

PMID- 29049952
TI  - Learn from microbial intelligence for avermectins overproduction.
AB  - Microbial strains are amazingly clever by homeostasis of their own survival and
      optimization for the overproduction of a desired phenotype, for example drugable
      secondary metabolites through coordination of key genes overexpression and media
      optimizations. Besides their pesticide activities, avermectins (AVMs) are
      identified as potent antibiotic agents for a wide range of drug-resistant
      pathogens by a high-throughput synergy screening strategy. To rewire the genetic
      circuitry controlling low yields, we summarized the work on balancing the
      biological chassis with functional parts, and optimized their dynamical process,
      as well as predicted favorable effective overproduction of AVMs by 5Ms strategy.
      AVMs are exclusively made in China now and intelligences learned from the success
      of AVMs will help transform microbes into a true power-house of innovation.

PMID- 29049953
TI  - Biomimetic fabrication of antibacterial calcium phosphates mediated by
      polydopamine.
AB  - In this work we developed new antibacterial composite materials using
      polydopamine (PDA) to trigger the deposition of silver nanoparticles (AgNPs) onto
      calcium phosphates, namely octacalcium phosphate (OCP) and alpha-tricalcium
      phosphate (alphaTCP). Functionalization of OCP and alphaTCP with a self
      polymerized polydopamine layer was obtained by soaking the calcium phosphates in
      dopamine solution. The PDA surface of functionalized calcium phosphates (OCPd and
      alphaTCPd) promoted the deposition of AgNPs by reducing silver ions when soaked
      in a silver nitrate solution. The amount of deposited AgNPs can be modulated by
      varying the concentration of silver nitrate solution and the type of substrate.
      The results of in vitro tests carried out with osteoblast-like MG63 cells
      indicate that the combination of AgNPs with OCP provides more biocompatible
      materials than those obtained using alphaTCP as substrate. In particular, the
      study of osteoblast activity and differentiation was focused on the samples
      OCPdAg5 (silver content=8.2wt%) and alphaTCPdAg5 (silver content=4.7wt%), which
      did not show any cytotoxicity, and compared with those obtained on pure OCP and
      alphaTCP. The results demonstrate that the AgNPs loaded materials support
      osteoblast viability and differentiation, whereas they significantly inhibit the
      growth of relevant antibiotic-resistant pathogenic bacteria.

PMID- 29049954
TI  - Application of Carnobacterium maltaromaticum as a feed additive for weaned
      rabbits to improve meat microbial quality and safety.
AB  - This study addresses the improvement of meat microbial quality by enriching the
      diet of farm animals with a protective culture. Weaned Grimaud rabbits were
      divided into two experimental groups: a control and a diet supplemented with
      Micocin(r) (Carnobacterium maltaromaticum CB1; 8Log10CFU/kg of feed). Overall,
      meat quality was not affected substantially by the treatment. Total Aerobic
      Mesophilic (TAM), Escherichia coli and other coliforms, Enterobacteriaceae,
      Staphylococcus aureus, Pseudomonas spp., Listeria spp. and presumptive lactic
      acid bacteria counts were evaluated on whole thighs stored under aerobic (0, 3,
      6, 8days) and anaerobic (0, 5, 10, 15, 20days) conditions at 4 degrees C. The
      results demonstrated that the microflora on refrigerated thighs was modulated by
      the addition of Micocin(r) (P<0.05) and that the most effective reduction of
      Listeria monocytogenes growth was observed with ground meat stored under
      anaerobic conditions at 4 degrees C with a 2 Log difference at the end of a 15
      day storage (P=0.025).

PMID- 29049955
TI  - THE ENGINE AND THE REAPER: INDUSTRIALIZATION AND MORTALITY IN LATE NINETEENTH
      CENTURY JAPAN.
AB  - Economic development improves long-run health outcomes through access to medical
      treatment, sanitation, and higher income. Short run impacts, however, may be
      ambiguous given disease exposure from market integration. Using a panel dataset
      of Japanese vital statistics and multiple estimation methods, I find that
      railroad network expansion is associated with a six percent increase in gross
      mortality rates among newly integrated regions. Communicable diseases accounted
      for most of the rail-associated mortality, which indicate railways behaved as
      transmission vectors. At the same time, market integration facilitated by
      railways corresponded with an eighteen percent increase in total capital
      investment nationwide over ten years.

PMID- 29049956
TI  - Adsorption and biodegradation of dye in wastewater with Fe3O4@MIL-100 (Fe) core
      shell bio-nanocomposites.
AB  - Adsorption and improved biodegradation of dyes in wastewater was achieved with
      Fe3O4@MIL-100 core-shell bio-nanocomposites, which were prepared by a step-by
      step strategy and attached to the surface of bacteria via zero-length
      carbodiimide chemistry. The Fe3O4@MIL-100 (Fe) nano-composite showed excellent
      dye adsorption properties and the overall dye removal process followed second
      order kinetics. The dye AO10 was completely eliminated from solution by the
      combined effects of adsorption and biodegradation within 15 and 25 h from initial
      dye concentrations of 25 and 50 mg/L, respectively. The time to degrade the dye
      decreased from 11 h for the free microorganisms to 5 h for the bio-nanocomposite.
      The procedure was non-toxic, allowed for magnetic separation of the bio
      nanocomposite from solution, and showed good cycling performance for the removal
      of dye. Hence, the strategy of surface-engineering bacteria shows great potential
      for the treatment of dyes from industrial effluents.

PMID- 29049957
TI  - Non-target impacts of soybean insecticidal seed treatments on the life history
      and behavior of Podisus nigrispinus, a predator of fall armyworm.
AB  - The treatment of seeds with systemic insecticides has become a common practice
      worldwide. However, this prophylactic use of insecticides has been questioned
      recently because of the potential risks to non-target organisms. This study
      assessed the non-target effects of chlorantraniliprole and thiamethoxam seed
      treatments on the life history and walking behavior of Podisus nigrispinus
      (Dallas), as well as the efficacy of these insecticides for controlling
      Spodoptera frugiperda (Smith). Thiamethoxam caused mortality of P. nigrispinus,
      increased the pre-oviposition period, and reduced the oviposition period and the
      fecundity and survival of females compared to chlorantraniliprole. In contrast,
      the life expectancy of P. nigrispinus females was prolonged by
      chlorantraniliprole, which also increased the intrinsic rate of growth (rm) and
      the finite growth rate (lambda), and reduced the population doubling time (DT)
      compared to thiamethoxam. The net reproductive rate (R0) and mean generation time
      (T) were not affected by either insecticide treatment, and neither were the
      walking velocity of P. nigrispinus females, nor the distance they covered. Both
      chlorantraniliprole and thiamethoxam reduced soybean leaf consumption by S.
      frugiperda larvae. Given the observed lethal and sublethal effects, soybean seed
      treatments with chlorantraniliprole and thiamethoxam were judged to present low
      and moderate risks for P. nigrispinus, respectively.

PMID- 29049958
TI  - Sublethal exposure to deltamethrin reduces the abilities of giant water bugs to
      prey upon Aedes aegypti larvae.
AB  - Freshwater ecosystems provide environmental conditions for many arthropod
      species, including pests like mosquitoes and beneficial insects. Giant water
      bugs, Belostoma anurum (Hemiptera: Belostomatidae), are aquatic insects that
      provide biological control of mosquitoes and small vertebrates in freshwater
      environments. However, the application of insecticides aiming to control
      mosquitoes can lead to insecticide exposures of aquatic predators that can result
      in their death or significant reductions in their behavioral abilities. Here, we
      assessed the susceptibilities of B. anurum to the pyrethroid insecticide
      deltamethrin and evaluated whether sublethal exposure to deltamethrin would
      change the abilities of B. anurum to prey upon larvae of Aedes aegypti (Diptera:
      Culicidae). Bioassays of predator performance were conducted at three prey
      densities (i.e., 3, 6 and 9 larvae/100 mL of water) just after insecticide
      exposure and on the three following days. Our results revealed that B. anurum
      (LC50 = 90.9 MUg a. i./L) was approximately 32-fold less susceptible to
      deltamethrin than A. aegypti larvae (LC50 = 2.8 MUg a. i./L). However, the number
      of larvae eaten by B. anurum sublethally exposed to deltamethrin (at 13 MUg a.
      i./L for 24 h) was significantly (P < 0.05) smaller than that recorded for
      unexposed predators. Furthermore, the deltamethrin-mediated behavioral changes
      were higher at the highest availability of prey and, as expected, just after
      insecticide exposure. Thus, sublethal exposure to deltamethrin reduces the
      ability of B. anurum to capture and prey upon A. aegypti larvae, compromising the
      efficacy of these insects as naturally occurring mosquito control agents.

PMID- 29049959
TI  - Excretion pattern and dynamics of glutathione detoxification of microcystins in
      Sprague Dawley rat.
AB  - The excretion route and dynamics of the glutathione (GSH) conjugate of
      microcystin-RR (MCRR), MCRR-GSH, were quantitatively studied in Sprague Dawley
      rat exposed with MCRR-GSH via liquid chromatography electrospray ionization mass
      spectrometry (LC-ESI-MS). In the MCRR-GSH-treated rat, the average MCRR-Cysteine
      (MCRR-Cys)/MCRR-GSH ratio reached as high as 105.3, which indicated that the
      intermediate conjugate MCRR-GSH was rapidly converted to the product compound
      MCRR-Cys. Besides, MCRR was consistently detected in MCRR-GSH-treated rat, which
      suggested that MCRR can be dissociated from the MCRR-GSH conjugate and the
      reversibility of the MC-GSH conjugate. Results of total MC contents analysis in
      excrement showed that the total MC contents in urine were significantly higher
      than those in feces. The ratio of the total MC content in urine to feces was as
      high as 129.3, which demonstrates that the urine is the main route of excretion
      after MCRR-GSH-treatment. In urine, the MCRR-Cys concentration was 27.8-fold,
      19.4-fold higher than MCRR-GSH and MCRR, respectively. Our results, for the first
      time, quantitatively found that MCRR-GSH was rapidly converted to MCRR-Cys after
      exposed to rat, and was excreted mainly through urine in the form of the MCRR-Cys
      conjugate. This study suggests that the GSH detoxification pathway of MCs could
      help to explain the greater sensitivity of mammals to MCs.

PMID- 29049960
TI  - Lethal effects of Cr(III) alone and in combination with propiconazole and
      clothianidin in honey bees.
AB  - Several anthropogenic contaminants, including pesticides and heavy metals, can
      affect honey bee health. The effects of mixtures of heavy metals and pesticides
      are rarely studied in bees, even though bees are likely to be exposed to these
      contaminants in both agricultural and urban environments. In this study, the
      lethal toxicity of Cr alone and in combination with the neonicotinoid insecticide
      clothianidin and the ergosterol-biosynthesis-inhibiting fungicide propiconazole
      was assessed in Apis mellifera adults. The LD50 and lowest benchmark dose of Cr
      as Cr(NO3)3, revealed a low acute oral toxicity on honey bee foragers (2049 and
      379 mg L-1, respectively) and the Cr retention (i.e. bee ability to retain the
      heavy metal in the body) was generally low compared to other metals. A modified
      method based on the binomial proportion test was developed to analyse synergistic
      and antagonistic interactions between the three tested contaminants. The
      combination of an ecologically-relevant field concentration of chromium with
      clothianidin and propiconazole did not increase bee mortality. On the contrary,
      the presence of Cr in mixture with propiconazole elicited a slight antagonistic
      effect.

PMID- 29049961
TI  - Smartphone app-based/portable sensor for the detection of fluoro-surfactant PFOA.
AB  - We developed a smartphone app-based monitoring tool for the detection of anionic
      surfactants (AS), including perfluorooctanoic acid (PFOA) and perfluorooctane
      sulfonate (PFOS). Akin to the methylene blue active substances (MBAS), liquid
      phase extraction (LPE) is employed to extract the hydrophobic ion-pair of dye
      (ethyl violet)-AS to an organic phase (ethyl acetate). The colour (RGB) of the
      organic phase is read using a smartphone camera with the help of a reading kit.
      The value of RGB is carefully corrected and linked to the concentration of ASs
      with a standard deviation of <10% in the 10-1000 ppb (part per billion) range. In
      order to avoid the interference arising from inorganic anions (such as those
      found in tap water and groundwater), the water sample is pre-treated either by
      solid-phase extraction (SPE), which takes ~30 min, or by dual liquid-phase
      extraction (dual-LPE, developed by us), which takes ~5 min. In the latter case,
      the organic phase of the first LPE (equilibrium with water sample) is transferred
      and subjected to a second LPE (equilibrium with Milli-Q water) to remove any
      potential background interference. In the meantime, SPE can also pre-concentrate
      ASs at 100-1000 times (in volume) to benefit the sensitivity. Consequently, our
      smartphone app can detect PFOA spiked in tap/groundwater with an LOD of 10 ppb
      (~12 nM, dual-LPE of ~5 min), or 0.5 ppb (~1.2 nM, SPE of ~3 h), suggesting that
      it has the potential to succeed as a pre-screening tool for on-site application
      and in common laboratory tests.

PMID- 29049962
TI  - Evaluation of methods for managing censored results when calculating the
      geometric mean.
AB  - Currently, there are conflicting views on the best statistical methods for
      managing censored environmental data. The method commonly applied by
      environmental science researchers and professionals is to substitute half the
      limit of reporting for derivation of summary statistics. This approach has been
      criticised by some researchers, raising questions around the interpretation of
      historical scientific data. This study evaluated four complete soil datasets, at
      three levels of simulated censorship, to test the accuracy of a range of censored
      data management methods for calculation of the geometric mean. The methods
      assessed included removal of censored results, substitution of a fixed value
      (near zero, half the limit of reporting and the limit of reporting), substitution
      by nearest neighbour imputation, maximum likelihood estimation, regression on
      order substitution and Kaplan-Meier/survival analysis. This is the first time
      such a comprehensive range of censored data management methods have been applied
      to assess the accuracy of calculation of the geometric mean. The results of this
      study show that, for describing the geometric mean, the simple method of
      substitution of half the limit of reporting is comparable or more accurate than
      alternative censored data management methods, including nearest neighbour
      imputation methods.

PMID- 29049964
TI  - The bit doesn't fit: Evaluation of a commercial activity-tracker at slower
      walking speeds.
AB  - Accelerometer-based commercial activity trackers are a low-cost and convenient
      method for monitoring and assessing health measures such as gait. However, the
      accuracy of these activity trackers in slow walking conditions on a minute-by
      minute basis is largely unknown. In this study, the accuracy of a hip-worn
      commercial activity tracker (FitBit Ultra) was examined through step counts.
      Accuracy was evaluated through four minute trials of treadmill walking at speeds
      representative of older adults (0.9, 1.1, and 1.3m/s). Minute-by-minute step
      count was extracted through the FitBit API and compared it to observer counted
      steps through video recordings. Results highlighted a significant over-reporting
      of steps at the highest speed, and a significant under-reporting of steps at the
      slowest speed, with the FitBit Ultra failing to count steps for one or more
      minutes at the slowest speed for 11 participants. This study highlights problems
      with using the FitBit Ultra by slow-walking populations, and recommends that
      researchers and clinicians should carefully consider the trade-off between
      accuracy and convenience when using commercial activity trackers with slow
      walking populations.

PMID- 29049963
TI  - Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of
      trypanosome proliferation.
AB  - Human African trypanosomiasis (HAT) is a deadly disease in need of new
      chemotherapeutics that can cross into the central nervous system. We previously
      reported the discovery of 2 (NEU-617), a small molecule with activity against T.
      brucei bloodstream proliferation. Further optimization of 2 to improve the
      physicochemical properties (LogP, LLE, [1], and MPO score) [2] have led us to
      twelve sub-micromolar compounds, most importantly the headgroup variants 9i and
      9j, and the linker variant 18. Although these 3 compounds had reduced potency
      compared to 2, they all had improved LogP, LLE and MPO scores. Cross-screening
      these analogs against other protozoan parasites uncovered 9o with potent activity
      towards T. brucei, T. cruzi and L. major, while four others compounds (17, 18,
      21, 26) showed activity towards P. falciparum D6. This reinforces the
      effectiveness of lead repurposing for the discovery of new protozoan disease
      therapeutics.

PMID- 29049965
TI  - Development of a molecular method for testing the effectiveness of UV systems on
      site.
AB  - We established a molecular method for quantifying ultraviolet (UV) disinfection
      efficacy using total bacterial DNA in a water sample. To evaluate UV damage to
      the DNA, we developed the "DNA damage" factor, which is a novel cultivation
      independent approach that reveals UV-exposure efficiency by applying a simple PCR
      amplification method. The study's goal was to prove the feasibility of this
      method for demonstrating the efficiency of UV systems in the field using flow
      through UV reactors. In laboratory-based experiments using seeded bacteria, the
      DNA damage tests demonstrated a good correlation between PCR products and UV
      dose. In the field, natural groundwater sampled before and after being subjected
      to the full-scale UV reactors was filtered, and the DNA extracted from the
      filtrate was subjected to PCR amplification for a 900-bp fragment of the 16S rRNA
      gene with initial DNA concentrations of 0.1 and 1 ng/MUL. In both cases, the UV
      dose predicted and explained a significant proportion of the variance in the log
      inactivation ratio and DNA damage factor. Log inactivation ratio was very low, as
      expected in groundwater due to low initial bacterial counts, whereas the DNA
      damage factor was within the range of values obtained in the laboratory-based
      experiments. Consequently, the DNA damage factor reflected the true performance
      of the full-scale UV system during operational water flow by using the indigenous
      bacterial array present in a water sample. By applying this method, we were able
      to predict with high confidence, the UV reactor inactivation potential. For
      method validation, laboratory and field iterations are required to create a
      practical field calibration curve that can be used to determine the expected
      efficiency of the full-scale UV system in the field under actual operation.

PMID- 29049966
TI  - Performance comparison of secondary and tertiary treatment systems for treating
      antibiotic resistance.
AB  - Rapid emergence of antibiotic resistance (AR) in developing countries is posing a
      greater health risk and increasing the global disease burden. AR proliferation
      mediated by treated/untreated discharges from sewage treatment plants (STPs) is a
      prime public health concern. Efficient sewage treatment is among our key defenses
      against the dissemination of infectious diseases. The present study aims to
      estimate the efficiency of aerobic [activated sludge process (ASP) and modified
      trickling filter (MTF)] and anaerobic reactors (anaerobic flow-through reactor)
      along with the three disinfection techniques (UV, ozone and chlorination) in
      reducing ARB and ARGs present in the domestic sewage. The three treatment systems
      were operated at different HRTs for 1 year and their performances in terms of
      treatment of conventional and emerging pollutants (ARB and ARGs) were assessed.
      The results indicated higher removal of ARB and ARGs in aerobic reactors compared
      to anaerobic reactor. Treatment studies in various bioreactors showed that the
      use of MTF along with UV/Ozone was superior to ASP and anaerobic flow-through
      reactor in reducing both the conventional and emerging pollutants. However,
      higher reduction of the pollutants was observed at higher HRTs. Though complete
      removal of coliforms and ARB was observed by treating the wastewater using MTF
      followed by UV or ozone but substantial levels of ARGs were observed in the
      effluent. Therefore, different advanced and effective treatment technologies such
      as filtration (RO), use of zero valent iron, TiO2 photocatalysis and other strong
      oxidizing agents which can ensure complete removal of ARGs along with ARB need to
      be evaluated. Though addition of these units will increase the treatment cost,
      but the increased cost would be negligible compared to the present disease burden
      of AR.

PMID- 29049967
TI  - Halogenated fatty amides - A brand new class of disinfection by-products.
AB  - An array of similar halogenated nitrogen-containing compounds with elemental
      composition CnH2nNO2X, CnH2n-2NO2X and CnH2n-1NOX2 (X = Cl, Br; n = 16, 18, 22)
      was detected in drinking water with high performance liquid chromatography - high
      resolution mass spectrometry (HPLC-HRMS) method. Compounds of this type were
      never mentioned among disinfection by-products. Tandem mass spectrometry allowed
      referring them to halohydrines or dihalogenated fatty amides, the products of
      conjugated electrophilic addition of halogens to the double bonds of unsaturated
      fatty amides. The proposed structures were confirmed by conducting aqueous
      chlorination with standard solution of oleamide. These compounds may be
      considered as a brand new class of disinfection by products, while their
      toxicities require special study.

PMID- 29049968
TI  - A novel Eulerian approach for modelling cyanobacteria movement: Thin layer
      formation and recurrent risk to drinking water intakes.
AB  - Toxic cyanobacteria (CB) blooms are being reported in an increasing number of
      water bodies worldwide. As drinking water (DW) treatment can be disrupted by CB,
      in addition to long term management plans, short term operational decision-making
      tools are needed that enable an understanding of the temporal variability of CB
      movement in relation to drinking water intakes. In this paper, we propose a novel
      conservative model based on a Eulerian framework and compare results with data
      from CB blooms in Missisquoi Bay (Quebec, Canada). The hydrodynamic model
      considered the effects of wind and light intensity, demonstrated that current
      understanding of cell buoyancy in relation to light intensity in full-scale
      systems is incomplete and some factors are yet to be fully characterized. Factors
      affecting CB buoyancy play a major role in the formation of a thin surface layer
      that could be of ecological importance with regards to cell concentrations and
      toxin production. Depending on velocities, wind contributes either to the
      accumulation or to the dispersion of CB. Lake recirculation effects have a
      tendency to create zones of low CB concentrations in a water body. Monitoring
      efforts and future research should focus on short-term variations of CB
      throughout the water column and the characterization of factors other than light
      intensity that affect cell buoyancy. These factors are critical for understanding
      the risk of breakthrough into treatment plants as well as the formation of
      surface scums and subsequent toxin production.

PMID- 29049969
TI  - The role of hydrodynamics in shaping the composition and architecture of
      epilithic biofilms in fluvial ecosystems.
AB  - Previous laboratory and on-site experiments have highlighted the importance of
      hydrodynamics in shaping biofilm composition and architecture. In how far
      responses to hydrodynamics can be found in natural flows under the complex
      interplay of environmental factors is still unknown. In this study we
      investigated the effect of near streambed turbulence in terms of turbulent
      kinetic energy (TKE) on the composition and architecture of biofilms matured in
      two mountainous streams differing in dissolved nutrient concentrations. Over both
      streams, TKE significantly explained 7% and 8% of the variability in biofilm
      composition and architecture, respectively. However, effects were more pronounced
      in the nutrient richer stream, where TKE significantly explained 12% and 3% of
      the variability in biofilm composition and architecture, respectively. While at
      lower nutrient concentrations seasonally varying factors such as stoichiometry of
      dissolved nutrients (N/P ratio) and light were more important and explained 41%
      and 6% of the variability in biofilm composition and architecture, respectively.
      Specific biofilm features such as elongated ripples and streamers, which were
      observed in response to the uniform and unidirectional flow in experimental
      settings, were not observed. Microbial biovolume and surface area covered by the
      biofilm canopy increased with TKE, while biofilm thickness and porosity where not
      affected or decreased. These findings indicate that under natural flows where
      near bed flow velocities and turbulence intensities fluctuate with time and
      space, biofilms became more compact. They spread uniformly on the mineral surface
      as a film of densely packed coccoid cells appearing like cobblestone pavement.
      The compact growth of biofilms seemed to be advantageous for resisting
      hydrodynamic shear forces in order to avoid displacement. Thus, near streambed
      turbulence can be considered as important factor shaping the composition and
      architecture of biofilms grown under natural flows.

PMID- 29049970
TI  - Sexual interest and sexual self-control in men with self-reported sexual interest
      in children - A first eye tracking study.
AB  - Sexual child abuse is one of the most destructive events for child development.
      One possible approach to avert it is the preventive treatment of individuals with
      a sexual interest in children. The aim of the current eye tracking study was to
      compare people with a self-reported sexual interest in children who participate
      in the outpatient preventive treatment project "PsM", pedophilic forensic
      inpatients, and a non-pedophilic control group. Groups were compared with respect
      to sexual interest and attentional control in the presence of sexual stimuli,
      both assessed independently of self-report. Two approaches were applied, namely
      the initial orientation approach for measuring sexual interest, and a sexual
      distractor task for measuring attentional control. Our data showed for the first
      time that outpatients with a self-reported sexual interest in children differed
      from pedophilic forensic inpatients with respect to attentional control but not
      with regard to sexual interest. Outpatients showed similar sexual interest in
      children as pedophilic forensic inpatients. They demonstrated significantly
      better attentional control than pedophilic forensic inpatients in the face of
      adult sexual stimuli, but the difference regarding child sexual stimuli did not
      reach significance. This might reflect a higher capacity for self-control and
      self-regulation in these patients. Nevertheless, child stimuli remain to be
      important distractors for them. Our results provide valuable additional
      information for the diagnosis and therapy of outpatients with a self-reported
      sexual interest in children. Obviously, these data are preliminary and further
      studies with larger groups should examine if they are replicable.

PMID- 29049971
TI  - Food addiction: Prevalence, psychopathological correlates and associations with
      quality of life in a large sample.
AB  - OBJECTIVE: To determine the prevalence of food addiction in a large Brazilian non
      clinical sample. Sociodemographic and psychopathological correlates of food
      addiction as well as associations with quality (QoL) domains were also
      investigated. METHODS: This cross-sectional study obtained data from a Brazilian
      anonymous web-based research platform (N = 7639; 71.3% females). Participants
      provided sociodemographic data and completed the modified Yale Food Addiction
      Scale 2.0, PHQ-9, hypomania checklist (HCL-32), Fagerstrom Test for Nicotine
      Dependence, AUDIT, modified Skin picking-Stanford questionnaire, Minnesota
      impulsive disorders interview, Symptom Checklist-90-Revised inventory (SCL-90R),
      early trauma inventory self report-short form, and the WHO Quality of Life
      instrument-Abbreviated version (WHOQOL-Bref). Associations were adjusted to
      potential confounders through multivariable models. RESULTS: The prevalence of
      food addiction was 4.32% (95%CI: 3.89-4.80%), and was more common among females.
      Food addiction was associated with a positive screen for a major depressive
      episode (OR = 4.41; 95%CI: 3.46-5.62), bipolar spectrum disorder (OR = 1.98;
      95%CI: 1.43-2.75), and skin picking disorder (OR = 2.02; 95%CI: 1.31-3.09). Food
      addiction was also independently associated with exposure to early life
      psychological and sexual abuse (P = 0.008) as well as with reduced physical,
      psychological, social, and environment QoL (all P < 0.001). CONCLUSIONS: Food
      addiction may be common in low and middle-income countries, though possibly less
      prevalent than in the US. Food addiction was associated with co-occurring mood
      disorders and skin picking disorder as well as with early life psychological and
      sexual abuse. Finally, food addiction was independently associated with broad
      reductions in QoL. Public health efforts towards the early recognition and
      management of food addiction are warranted.

PMID- 29049972
TI  - Noble metals decorated hierarchical maghemite magnetic tubes as an efficient
      recyclable catalyst.
AB  - The noble metal nanocatalysts on high surface area magnetic material supports
      have huge technological importance in the field of catalysis. The green synthesis
      of magnetic-noble metal hybrid material has another technological importance. In
      this study, we report a novel, efficient, and sustainable synthesis methodology
      for Au nanoparticles (NPs) deposited hierarchical magnetic maghemite (gamma
      Fe2O3) tubes. In this methodology, the green tea extract was used as a reducing
      agent for both iron oxide and Au NPs synthesis. The natural cotton fibers were
      used as a sacrificial template to obtain porous and high surface area (90m2/g)
      magnetic gamma-Fe2O3 tubes. Further, the Au NPs (7+/-2nm) were in situ deposited
      onto the tubes surface after reduction of Au salt by green tea extract. The XPS
      spectra was confirmed the presence of negatively charged Au on the iron oxide
      supports due to charge transfer process and strong metal-support material
      electronic interaction. The Au NPs decorated gamma-Fe2O3 tubes were possessed
      18emu/g saturation magnetization at room temperature which is large enough for
      the magnetic separation. The synthesized material was showed very good catalytic
      activity for the hydrogenation reaction of 4-nitrophenol to aminophenol
      conversion. As the catalyst has very good magnetic property, the reusability of
      catalyst was checked after magnetic separation and found only 0.29% reduction in
      catalytic activity after the sixth cycle. Further, the Ag and Pd NPs decorated
      gamma-Fe2O3 tubes were also synthesized and tested for the same catalytic
      reaction and found the highest activity for Pd.

PMID- 29049973
TI  - Semi-analytical representation of the activation level in stress fibre directions
      as alternative to the angular representation in the bio-chemo-mechanical model
      for cell contractility.
AB  - The bio-chemo-mechanical model has many applications in modelling cell
      contractility. In simulations this model usually is coupled to the continuum
      mechanics of the cell by defining a large number of directions for stress fibres
      at each point. In this paper, another representation for coupling the biochemical
      processes in the bio-chemo-mechanical model is introduced. Using a quadratic form
      to represent the angular dependency of the activation level, the model's number
      of degrees of freedom is significantly reduced. Numerical results similar to the
      original representation are obtained while a significant improvement in
      computation time is achieved.

PMID- 29049974
TI  - Photolysis study of octyl p-methoxycinnamate loaded microemulsion by molecular
      fluorescence and chemometric approach.
AB  - Octyl p-methoxycinnamate (OMC) is one of the most widely used sunscreen agents.
      However, the efficiency of OMC as UV filter over time is affected due to the
      formation of the cis-isomer which presents a markedly lower extinction
      coefficient (epsiloncis=12,600L mol-1cm-1 at 291nm) than the original trans
      isomer (epsilontrans=24,000L mol-1cm-1 at 310nm). In this work, a novel carrier
      for OMC based on an oil-in-water microemulsion is proposed in order to improve
      the photostability of this sunscreen. The formulation was composed of 29.2% (w/w)
      of a 3:1 mixture of ethanol (co-surfactant) and decaethylene glycol mono-dodecyl
      ether (surfactant), 1.5% (w/w) of oleic acid (oil phase) and 69.2% (w/w) of
      water. This microemulsion was prepared in a simple way, under moderate stirring
      at 25 degrees C and using acceptable, biocompatible and accessible materials for
      topical use. OMC was incorporated in the vehicle at a final concentration of 5.0%
      (w/w), taking into account the maximum permitted levels established by
      international norms. Then, a photolysis study of the loaded formulation was
      performed using a continuous flow system. The direct photolysis was monitored
      over time by molecular fluorescence. The recorded spectra data between 370 y
      490nm were analyzed by multivariate curve resolution-alternating least squares
      algorithm. The kinetic rate constants corresponding to the photolysis of the
      trans-OMC were calculated from the concentration profiles, resulting in 0.0049s-1
      for the trans-OMC loaded microemulsion and 0.0131s-1 for the trans-OMC in aqueous
      media. These results demonstrate a higher photostability of the trans-OMC when
      loaded in the proposed vehicle with respect to the free trans-OMC in aqueous
      media.

PMID- 29049975
TI  - The electric field standing wave effect in infrared transflection spectroscopy.
AB  - We show that an electric field standing wave effect is responsible for the
      oscillations and the non-linear dependence of the absorbance on the layer
      thickness in thin layers on a reflective surface. This effect is connected to the
      occurrence of interference inside these layers. Consequently, the absorptance
      undergoes a maximum electric field intensity enhancement at spectral positions
      close to those where corresponding non-absorbing layers on a metal show minima in
      the reflectance. The effect leads to changes of peak maxima ratios with layer
      thickness and shows the same periodicity as oscillations in the peak positions.
      These peculiarities are fully based on and described by Maxwell's equations but
      cannot be understood and described if the strongly simplifying model centered on
      reflectance absorbance is employed.

PMID- 29049976
TI  - Sodium valproate enhances doxorubicin-induced cognitive dysfunction in Wistar
      rats.
AB  - BACKGROUND: Increasing number of scientific reports have highlighted the role of
      histone acetylation/deacetylation in neurodegenerative conditions, including
      chemotherapy-induced cognitive dysfunction (also known as chemobrain). Multiple
      sources state that increased activity of histone deacetylases (HDACs) play a
      detrimental role in chemobrain. In the present study, sodium valproate, a well
      known HDAC inhibitor, was explored for its neuroprotective potential against
      chemobrain development. METHODS: Doxorubicin (DOX), a chemotherapeutic agent, was
      used to induce chemobrain in experimental animals while treating with sodium
      valproate simultaneously. The animals were subjected to novel object recognition
      test (NORT) in order to assess their cognitive status and further, brain
      antioxidant levels were estimated. The animal body weights and survival were
      noted throughout the period of the study. Blood parameters such as red blood cell
      count, white blood cell count and haemoglobin levels were also measured. RESULTS:
      Our findings are in contradiction to the known neuroprotective properties of
      valproic acid. We observed that sodium valproate failed to prevent chemobrain
      development in DOX treated animals. In fact, treatment with sodium valproate dose
      dependently worsened cognitive status in DOX treated animals including their
      brain antioxidant status, possibly leading to neuronal damage through free
      radical induced toxicity. CONCLUSION: The present study highlights the caution
      that needs to be exercised in projecting HDAC inhibitors as in vivo
      neuroprotective agents, due to the complexity of existing neurological pathways
      and the diverse roles of histone deacetylases.

PMID- 29049977
TI  - Syk - GTP RAC-1 mediated immune-stimulatory effect of Cuscuta epithymum, Ipomoea
      batata and Euphorbia hirta plant extracts.
AB  - Polymorphonuclear neutrophils (PMNn) are the pivotal mediators of phagocytosis.
      In addition to neutropenia, impaired neutrophilic function is associated with
      pathological conditions and immuno-deficiencies. Henceforth, Immuno-stimulatory
      strategies targeting neutrophilic function are indeed powerful tools in combating
      obstinate infections. In appreciation towards the usefulness of herbal medicines
      in therapeutic scenario, the present study was carried out to analyse the immuno
      stimulatory effect of Cuscuta epithymum, Ipomoea batata and Euphorbia hirta using
      in-vitro and in-vivo rodent experimental models. Throughout the experimentation,
      phagocytosis was studied and expressed as phagocytotic index and percentage
      phagocytosis. Different extracts of these plants were initially screened for
      their potency to induce phagocytosis in PMNn and the methanolic fractions, which
      are effective, were considered for further experimentation.The phagocytosis
      stimulation by the methanolic extracts was compared with the standard Granulocyte
      Macrophage - Colony Stimulating Factor (GM-CSF) at a dose of 65ng/ml.
      Immunoblotting analysis shown that the methanolic extracts induce the
      phosphorylation of Syk which in turn phosphorylates GDP-RAC-1, hinting the
      possible mechanism of action. Following these in vitro investigations, the
      potency of methanolic extracts was assessed using rat model by performing carbon
      clearance assay, Delayed Type Hypersensitivity and antibody titre.The
      phosphorylation status of Syk and GDP-RAC-1 was also assessed in the edematous
      fluid collected from the right hind paw. In vivo findings were in agreement with
      the in vitro findings by presenting an improved immune response and increased
      phosphorylation of Syk and GDP-RAC-1. Conclusively, this study provides the
      initial insights into the therapeutic implications of the tropical plants in
      inducing phagocytosis.

PMID- 29049978
TI  - Targeting eIF4E inhibits growth, survival and angiogenesis in retinoblastoma and
      enhances efficacy of chemotherapy.
AB  - Although the eukaryotic translation initiation factor 4E (eIF4E) has been shown
      to be critically involved in the transformation and progression of various
      tumors, little is known about the role of eIF4E in retinoblastoma. In this work,
      we report that ribavirin, a pharmacologic inhibitor of eIF4E function,
      effectively targets retinoblastoma and angiogenesis. Ribavirin treatment dose
      dependently blocked the growth and stimulated apoptosis in various retinoblastoma
      cell lines, with IC50 values that are within the clinically achievable range.
      Ribavirin also significantly inhibited angiogenesis via disrupting capillary
      network formation and suppressing VEGF-induced migration, proliferation and
      survival of human retinal endothelial cells. In addition, ribavirin significantly
      augments chemotherapy agent's inhibitory effects in retinoblastoma in vitro and
      in vivo. Mechanistically, ribavirin inhibited eIF4E function in retinoblastoma
      cells as shown by the decreased protein levels of Cyclin D1, c-Myc and VEGF
      without affecting their mRNA expression. Overexpression of the wildtype and
      phosphormimetic but not the nonphosphorylatable form of eIF4E significantly
      abolished the inhibitory effects of ribavirin, further demonstrating eIF4E as the
      target of ribavirin. Genetic knockdown of eIF4E using two independent siRNAs
      mirrored ribavirin's effects, confirming the role of eIF4E in retinoblastoma
      growth, survival and response to chemotherapy. Our findings provide a preclinical
      rationale to explore ribavirin as a strategy to treat retinoblastoma and
      highlight the therapeutic value of targeting eIF4E in retinoblastoma.

PMID- 29049979
TI  - Triptonide inhibits the pathological functions of gastric cancer-associated
      fibroblasts.
AB  - Direct attacks on tumour cells with chemotherapeutic drugs have the drawbacks of
      accelerating tumour metastasis and inducing tumour stem cell phenotypes.
      Inhibition of tumour-associated fibroblasts, which provide nourishment and
      support to tumour cells, is a novel and promising anti-tumour strategy. However,
      effective drugs against tumour-associated fibroblasts are currently lacking. In
      the present study, we explored the possibility of inhibiting the pathological
      functions of tumour-associated fibroblasts with triptonide. Paired gastric normal
      fibroblasts (GNFs) and gastric cancer-associated fibroblasts (GCAFs) were
      obtained from resected tissues. GCAFs showed higher capacities to induce colony
      formation, migration, and invasion of gastric cancer cells than GNFs. Triptonide
      treatment strongly inhibited the colony formation-, migration-, and invasion
      promoting capacities of GCAFs. The expression of microRNA-301a was higher and
      that of microRNA-149 was lower in GCAFs than in GNFs. Triptonide treatment
      significantly down-regulated microRNA-301a expression and up-regulated microRNA
      149 expression in GCAFs. Re-establishment of microRNA expression balance
      increased the production and secretion of tissue inhibitor of metalloproteinase
      2, a tumour suppressive factor, and suppressed the production and secretion of IL
      6, an oncogenic factor, in GCAFs. Moreover, triptonide treatment abolished the
      ability of GCAFs to induce epithelial-mesenchymal transition in gastric cancer
      cells. These results indicate that triptonide inhibits the malignancy-promoting
      capacity of GCAFs by correcting abnormalities in microRNA expression. Thus,
      triptonide is a promisingly therapeutic agent for gastric cancer treatment, and
      traditional herbs may be a valuable source for developing new drugs that can
      regulate the tumour microenvironment.

PMID- 29049980
TI  - The dual role of poly(ADP-ribose) polymerase-1 in modulating parthanatos and
      autophagy under oxidative stress in rat cochlear marginal cells of the stria
      vascularis.
AB  - Oxidative stress is reported to regulate several apoptotic and necrotic cell
      death pathways in auditory tissues. Poly(ADP-ribose) polymerase-1 (PARP-1) can be
      activated under oxidative stress, which is the hallmark of parthanatos.
      Autophagy, which serves either a pro-survival or pro-death function, can also be
      stimulated by oxidative stress, but the role of autophagy and its relationship
      with parthanatos underlying this activation in the inner ear remains unknown. In
      this study, we established an oxidative stress model in vitro by glucose
      oxidase/glucose (GO/G), which could continuously generate low concentrations of
      H2O2 to mimic continuous exposure to H2O2 in physiological conditions, for
      investigation of oxidative stress-induced cell death mechanisms and the
      regulatory role of PARP-1 in this process. We observed that GO/G induced stria
      marginal cells (MCs) death via upregulation of PARP-1 expression, accumulation of
      polyADP-ribose (PAR) polymers, decline of mitochondrial membrane potential (MMP)
      and nuclear translocation of apoptosis-inducing factor (AIF), which all are
      biochemical features of parthanatos. PARP-1 knockdown rescued GO/G-induced MCs
      death, as well as abrogated downstream molecular events of PARP-1 activation. In
      addition, we demonstrated that GO/G stimulated autophagy and PARP-1 knockdown
      suppressed GO/G-induced autophagy in MCs. Interestingly, autophagy suppression by
      3-Methyladenine (3-MA) accelerated GO/G-induced parthanatos, indicating a pro
      survival function of autophagy in GO/G-induced MCs death. Taken together, these
      data suggested that PARP-1 played dual roles by modulating parthanatos and
      autophagy in oxidative stress-induced MCs death, which may be considered as a
      promising therapeutic target for ameliorating oxidative stress-related hearing
      disorders.

PMID- 29049981
TI  - Angiotensin receptor blockade improves cardiac mitochondrial activity in response
      to an acute glucose load in obese insulin resistant rats.
AB  - Hyperglycemia increases the risk of oxidant overproduction in the heart through
      activation of a multitude of pathways. Oxidation of mitochondrial enzymes may
      impair their function resulting in accumulation of intermediates and reverse
      electron transfer, contributing to mitochondrial dysfunction. Furthermore, the
      renin-angiotensin system (RAS) becomes inappropriately activated during metabolic
      syndrome, increasing oxidant production. To combat excess oxidant production, the
      transcription factor, nuclear factor erythriod-2- related factor 2 (Nrf2),
      induces expression of many antioxidant genes. We hypothesized that angiotensin II
      receptor type 1 (AT1) blockade improves mitochondrial function in response to an
      acute glucose load via upregulation of Nrf2. To address this hypothesis, an oral
      glucose challenge was performed in three groups prior to dissection (n = 5-8
      animals/group/time point) of adult male rats: 1) Long Evans Tokushima Otsuka
      (LETO; lean strain-control), 2) insulin resistant, obese Otsuka Long Evans
      Tokushima Fatty (OLETF), and 3) OLETF + angiotensin receptor blocker (ARB; 10mg
      olmesartan/kg/d * 6 weeks). Hearts were collected at T0, T60, and T120 minutes
      post-glucose infusion. ARB increased Nrf2 binding 32% compared to OLETF at T60.
      Total superoxide dismutase (SOD) and catalase (CAT) activities were increased 45%
      and 66% respectively in ARB treated animals compared to OLETF. Mitochondrial
      enzyme activities of aconitase, complex I, and complex II increased by 135%, 33%
      and 66%, respectively in ARB compared to OLETF. These data demonstrate the
      protective effects of AT1 blockade on mitochondrial function during the
      manifestation of insulin resistance suggesting that the inappropriate activation
      of AT1 during insulin resistance may impair Nrf2 translocation and subsequent
      antioxidant activities and mitochondrial function.

PMID- 29049982
TI  - Characterization of soluble microbial products in a partial nitrification
      sequencing batch biofilm reactor treating high ammonia nitrogen wastewater.
AB  - In present study, the characterization of soluble microbial products (SMP) was
      evaluated in a partial nitrification sequencing batch biofilm reactor (SBBR).
      During the stable operation of SBBR, the NH4+-N removal efficiency and nitrite
      accumulation ratio were 96.70+/-0.41% and 93.77+/-1.04%, respectively. According
      to excitation-emission matrix (EEM), the intensities of protein-like substances
      were reduced under anoxic and aerobic phases, whereas humic-like substances had
      little change during the whole cycle. Parallel factor analysis (PARAFAC) further
      indentified two components and their fluorescence intensity scores were both
      reduced. Synchronous fluorescence spectra revealed that the fluorescence
      intensity of protein-like fraction decreased with reaction time. Two-dimensional
      correlation spectroscopy (2D-COS) further demonstrated that protein-like fraction
      might decrease earlier than the other fractions. The information obtained in
      present study is of fundamental significance for understanding the key components
      in SMP and their changes in partial nitrification system by using a spectral
      approach.

PMID- 29049983
TI  - Investigation on biomass nitrogen-enriched pyrolysis: Influence of temperature.
AB  - Biomass (bamboo waste) nitrogen-enriched pyrolysis was carried out in a fixed bed
      with NH3 atmosphere at 400-800  degrees C, and formation mechanism of N
      containing species was explored in depth. Results showed that N-enriched
      pyrolysis greatly increased bio-oil and gas yields. H2 yield increased sharply to
      130 mL/g (32.93 vol%) and became the main composition at higher temperature,
      while CH4 and CO yields deceased, and the lower heating value of gas reached ~14
      MJ/Nm3. For bio-oil, the content of phenols (main compositions) and N-containing
      species increased significantly, and the maximums reached 61.33% and 11.47%,
      respectively. While that of acetic acid (disappeared), O-containing species
      (aldehydes/ketones/furans/esters) and aromatics decreased largely accordingly.
      For biochar, Nitrogen content increased, and it contained abundant pyridininc-N,
      pyrrolic-N, quaternary-N, and pyridone-N-oxide. Possible reaction pathways of
      biomass N-enriched pyrolysis was proposed based on products evolution. In
      conclusion, biomass N-enriched pyrolysis could obtain high-valued N-containing
      chemical species and functional biochar.

PMID- 29049984
TI  - Effect of Thiobacillus thioparus 1904 and sulphur addition on odour emission
      during aerobic composting.
AB  - The effects of sulphur and Thiobacillus thioparus 1904 on odour emissions during
      composting were studied. Results indicated that the sulphur addition reduced the
      pH and decreased cumulative emission of ammonia and the nitrogen loss by 47.80%
      and 44.23%, respectively, but the amount of volatile sulphur compounds (VSCs) and
      the sulphur loss increased. The addition of T. thioparus 1904 effectively reduced
      the cumulative emissions of H2S, methyl sulphide, methanethiol, dimethyl
      disulphide and the sulphur loss by 33.24%, 81.24%, 32.70%, 54.22% and 54.24%,
      respectively. T. thioparus 1904 also limited the nitrogen loss. The combined
      application of sulphur and T. thioparus 1904 resulted in the greatest amount of
      nitrogen retention. The accumulation of ammonia emissions was reduced by 63.33%,
      and the nitrogen loss was reduced by 71.93%. The combined treatment did not
      increase the emission of VSCs. The application of sulphur and T. thioparus 1904
      may help to control the odour of compost.

PMID- 29049985
TI  - Insight into the structure-function relationships of deep eutectic solvents
      during rice straw pretreatment.
AB  - Rice straw pretreatment mediated by choline chloride (ChCl) or lactic acid (Lac)
      sequences deep eutectic solvents (DESs) was investigated in this work. Hydrogen
      bond acceptors (HBAs) and hydrogen bond donors (HBDs) proved to be both important
      for DESs pretreatment efficiency. DESs containing lots of hydroxyl or amino
      groups with a high intermolecular hydrogen-bond (H-bond) strength exhibited weak
      biomass deconstruction abilities. The presence of strong electron-withdrawing
      groups in DESs was benefit for xylan removal, thus furnishing higher cellulose
      digestibility. The relationships between the properties of DESs, xylan removal
      and cellulose digestibility of pretreated biomass were established. It was found
      that xylan removal was negatively correlated with the pKa values of HBDs, and the
      enzymatic cellulose digestibility of the residues was linearly and positively
      related to xylan removal instead of delignification. These results provide a
      preliminary reference for rational design of novel DESs for biomass pretreatment.

PMID- 29049986
TI  - New Diagnostic Criteria of Polycystic Ovarian Morphology for Adolescents: Impact
      on Prevalence and Hormonal Profile.
AB  - BACKGROUND: The ultrasonographic criteria used to identify polycystic ovarian
      morphology (PCOM) during adolescence have changed over time. Recently, a
      Worldwide Pediatric Consensus (PedC) defined PCOM using stricter criteria than
      the previous recommendations of the Rotterdam Consensus (RC) and Androgen Excess
      Polycystic Ovarian Syndrome Society (AES/PCOS) criteria. The aim of this study
      was to determine the prevalence of PCOM in healthy adolescents according to the 3
      reported diagnostic criteria and compare the hormonal profile in females with and
      without PCOM based on the PedC criteria. METHODS: Nonobese adolescents (n = 102)
      with regular menstrual cycles were studied. Transabdominal ultrasound and
      hormonal profiles were assessed during the follicular phase. PCOM was defined on
      the basis of the 3 published criteria. RESULTS: On the basis of the PedC, RC, and
      AES/PCOS criteria, PCOM was diagnosed in 13, 34, and 24% of adolescents,
      respectively. Adolescents with and without PCOM according to the PedC criteria
      had similar androgen levels. Serum anti-Mullerian hormone (AMH) levels were
      elevated in adolescents with PCOM, irrespective of the criteria used.
      CONCLUSIONS: Use of the new PedC diagnostic criteria for PCOM results in a lower
      prevalence of this ultrasonographic pattern in adolescents, but this condition is
      not associated with hyperandrogenism. Elevated AMH is associated with PCOM in
      adolescents regardless of the criteria used to determine the ultrasonographic
      pattern.

PMID- 29049987
TI  - Isoflavones Induce BEX2-Dependent Autophagy to Prevent ATR-Induced Neurotoxicity
      in SH-SY5Y Cells.
AB  - BACKGROUND/AIMS: Atrazine (ATR) is a broad-spectrum herbicide in wide use around
      the world. However, ATR is neurotoxic and can cause cell death in dopaminergic
      neurons, leading to neurodegenerative disorders. Autophagy is the basic cellular
      catabolic process involving the degradation of proteins and damaged organelles.
      Studies have shown that certain plant compounds can induce autophagy and prevent
      neuronal cell death. This prompted us to investigate plant compounds that might
      reduce the neurotoxic effects of ATR. METHODS: By CCK-8 and flow cytometry, we
      tested the ability of five candidate compounds-isoflavones, resveratrol,
      quercetin, curcumin, and green tea polyphenols-to protect cells from ATR. Changes
      in the expression of tyrosine hydroxylase (TH) and brain-expressed X-linked 2
      (BEX2), autophagy-related proteins and key factors in mTOR signaling, were
      detected by Western blotting. RESULTS: Isoflavones had the strongest activity
      against ATR-induced neuronal apoptosis. ATR reduced the expression of TH and
      BEX2, whereas isoflavones increased TH and BEX2 expression. In addition, ATR
      inhibited autophagy, whereas isoflavones induced autophagy through the
      accumulation of LC3-II and decreased expression of p62; this effect was abolished
      by 3-methyladenine (3-MA). Furthermore, BEX2 siRNA abolished isoflavone-mediated
      autophagy and neuroprotection in vitro. CONCLUSION: Isoflavones activate BEX2
      dependent autophagy, protecting against ATR-induced neuronal apoptosis.

PMID- 29049988
TI  - Magnolia Officinalis Bark Extract Induces Depolarization of Pacemaker Potentials
      Through M2 and M3 Muscarinic Receptors in Cultured Murine Small Intestine
      Interstitial Cells of Cajal.
AB  - BACKGROUND: Magnolia officinalis Rehder and EH Wilson (M. officinalis) are
      traditional Chinese medicines widely used for gastrointestinal (GI) tract
      motility disorder in Asian countries. We investigated the effects of an ethanol
      extract of M. officinalis (MOE) on the pacemaker potentials of cultured
      interstitial cells of Cajal (ICCs) in vitro and its effects on GI motor functions
      in vivo. METHODS: We isolated ICCs from small intestines, and the whole-cell
      patch-clamp configuration was used to record the pacemaker potentials in cultured
      ICCs in vitro. Both gastric emptying (GE) and intestinal transit rates (ITRs)
      were investigated in normal and GI motility dysfunction (GMD) mice models in
      vivo. RESULTS: MOE depolarized ICC pacemaker potentials dose-dependently.
      Pretreatment with methoctramine (a muscarinic M2 receptor antagonist) and 4-DAMP
      (a muscarinic M3 receptor antagonist) inhibited the effects of MOE on the
      pacemaker potential relative to treatment with MOE alone. In addition, MOE
      depolarized pacemaker potentials after pretreatment with Y25130 (a 5-HT3 receptor
      antagonist), GR113808 (a 5-HT4 receptor antagonist) or SB269970 (a 5-HT7 receptor
      antagonist). However, pretreatment with RS39604 (a 5-HT4 receptor antagonist)
      blocked MOE-induced pacemaker potential depolarizations. Intracellular GDPbetaS
      inhibited MOE-induced pacemaker potential depolarization, as did pretreatment
      with Ca2+ free solution or thapsigargin. In normal mice, the GE and ITR values
      were significantly and dose-dependently increased by MOE. In loperamide-and
      cisplatin-induced GE delay models, MOE administration reversed the GE deficits.
      The ITRs of the GMD mice were significantly reduced relative to those of normal
      mice, which were significantly and dose-dependently reversed by MOE. CONCLUSION:
      These results suggest that MOE dose-dependently depolarizes ICCs pacemaker
      potentials through M2 and M3 receptors via internal and external Ca2+ regulation
      through G protein pathways in vitro. Moreover, MOE increased GE and ITRs in vivo
      in normal and GMD mouse models. Taken together, the results of this study show
      that MOE have the potential for development as a gastroprokinetic agent in GI
      motility function.

PMID- 29049989
TI  - The USP7 Inhibitor P5091 Induces Cell Death in Ovarian Cancers with Different P53
      Status.
AB  - BACKGROUND/AIMS: Ovarian cancer is often diagnosed at later stages with poor
      prognosis. Recent studies have associated the expression of deubiquitylase USP7
      with the survival of ovarian cancers. Being a cysteine protease, USP7 could
      become a target for pharmacological intervention. Therefore, in this study, we
      assessed the influence of its inhibitor P5091 on ovarian cancer cells. METHODS:
      Ovarian cancer cells were treated with P5091, and cell proliferation was measured
      with MTT assay; cell morphology was inspected under a phase-contrast microscope;
      cell cycle and cell death were examined by flow cytometry. To gain mechanistic
      insights into its effects, immunoblotting was performed to detect USP7, HDM2,
      p53, p21, apoptosis and autophagy related proteins. RESULTS: P5091 effectively
      suppressed the growth of ovarian cancer cells, caused cell cycle blockage, and
      induced necrosis and apoptosis with more severe phenotypes observed in HeyA8
      cells with wild-type p53 than in OVCAR-8 cells with mutant p53. P5091 also
      prompted autophagy, with more efficient p62 degradation in HeyA8. CONCLUSION:
      P5091 shows efficacy in suppressing ovarian cancers harbouring wild-type and
      mutant p53. Its effects seemed to be enhanced by wild-type p53. The potency of
      this USP7 inhibitor also correlated with autophagy to some extent. Therefore, the
      pharmacological targeting of USP7 may serve as a potential therapeutic strategy
      and warrants further investigation.

PMID- 29049990
TI  - Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia
      Reperfusion-Induced Acute Kidney Injury.
AB  - BACKGROUND: Renal fibrosis is a common pathophysiological feature of chronic
      kidney disease. Acute kidney injury (AKI) is defined as an independent causal
      factor of chronic kidney disease, with a pathological representation of post
      renal fibrosis. However, the etiopathogenesis underlying post renal fibrosis
      induced by AKI is not completely understood. METHODS: BALB/c mice were treated
      with bpv or vehicle controls and were, respectively, the ischemia reperfusion
      (IR) model group and control group. All of the animals had blood taken from the
      orbital venous plexus at 24 hours after IR. Six mice in each group were randomly
      chosen and euthanized 7 days after IR treatment, and the remaining six mice in
      each group were euthanized 14 days after IR treatment. We examined the effect on
      post kidney fibrosis of inhibiting PTEN activity in mice in an IR induced AKI
      experimental model. RESULTS: Compared with vehicle mice, bpv-(PTEN specific
      inhibitor) treated mice accumulated more bone marrow-derived fibroblasts and
      myofibroblasts in the kidneys. Inhibition of PTEN activity increased the
      expression of alpha-smooth muscle actin and extracellular matrix proteins and
      post kidney fibrosis. Furthermore, inhibition of PTEN activity resulted in more
      inflammatory cytokines in the kidneys of mice subjected to IR-induced renal
      fibrosis. Moreover, inhibition of PTEN activity up-regulated PI3K protein
      expression and Akt phosphorylation. CONCLUSIONS: Our study demonstrated that PTEN
      played an important role in post renal fibrosis in mice with ischemia reperfusion
      induced AKI. These results indicated that the PTEN/PI3K/Akt signaling pathway may
      serve as a novel therapeutic target for AKI-induced chronic kidney disease.

PMID- 29049991
TI  - Comparison of Quality of Life in Patients Undergoing Hemodialysis and Peritoneal
      Dialysis: a Systematic Review and Meta-Analysis.
AB  - BACKGROUND/AIMS: The increase in the survival rate of patients with chronic renal
      failure due to substitution treatment prompts an investigation of their quality
      of life (QoL), a key measure to evaluate the outcomes of chronic disease
      treatment. To determine whether hemodialysis or peritoneal dialysis provide a
      better QoL, a systematic meta-analysis was performed. METHODS: We searched
      through the database Cinahl, Medline, PubMed, Scopus and Proquest, including
      articles published from 2011 until June 2016. We selected articles that compared,
      through KDQOL-SF 1.3 or 36 questionnaires, QoL among patients undergoing
      hemodialysis and peritoneal dialysis. The data was collected using Excel Office,
      and t-test has been performed on independent samples to identify significant
      differences. RESULTS: Only some of the seven articles found significant
      differences between the two treatments. One of the studies showed a better QoL
      for peritoneal dialysis patients, while, on the contrary, two other studies
      support that the best QoL is in patients receiving hemodialysis. Another article
      displayed significant difference only for satisfaction in relation to care,
      better in patients on peritoneal dialysis, and for physical health, better in
      hemodialysis. CONCLUSIONS: The analysis has not led to a unanimous conclusion.
      Quantitative analysis showed that the only statistically significant difference
      between the QoL of patients on hemodialysis and peritoneal dialysis regards the
      effect of kidney disease, which happens to be better in patients undergoing
      peritoneal dialysis.

PMID- 29049992
TI  - Iridoids with Genipin Stem Nucleus Inhibit Lipopolysaccharide-Induced
      Inflammation and Oxidative Stress by Blocking the NF-kappaB Pathway in Polycystic
      Ovary Syndrome.
AB  - BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder
      in women, and it is usually characterized by chronic inflammation, oxidative
      stress, and altered microRNA expression. The aim of this study is to investigate
      how the effects of iridoids with genipin stem nucleus inhibit PCOS complications.
      The interactions between iridoids were investigated, as well. METHODS: The
      chronic inflammation cell model was induced using lipopolysaccharide (LPS) in the
      RAW 264.7 and KGN cell lines. Levels of mRNA and protein expression were
      quantified using real time-quantitative polymerase chain reaction (RT-qPCR) and
      western blot analysis, respectively. The target of the iridoids was identified
      using the drug affinity responsive target stability (DARTS) method. The ability
      to scavenge free radicals was evaluated using the DPPH radical scavenging method
      and the ultra oxygen anion (O2-) radical scavenging method. RESULTS: The cells
      recovered from the inflammatory conditions and showed significantly decreased
      levels of interleukins after treatment with iridoids. The iridoids were
      demonstrated to target NF-kappaB, inhibit the phosphorylation and degradation of
      IkappaB, inhibit the nuclear entry of NF-kappaB, and inhibit the expression of
      inflammatory factors. Though only genipin showed an efficient ability to scavenge
      O2-, the iridoids, IkappaB inhibitor (BAY 11-7085), and NF-kappaB inhibitor
      (PDTC) could inhibit LPS-induced oxidative stress on the cells, indicating that
      the iridoids exert their anti-oxidant effects via the NF-kappaB pathway. The
      expression levels of microRNAs (miRNAs) were also altered by LPS, but the
      iridoids could scarcely rescue the abnormal condition. CONCLUSION: Chronic
      inflammation may be an important incentive for oxidative stress and abnormal
      microRNA expression in PCOS, and iridoids can protect patients from inflammatory
      damage by regulating the NF-kappaB pathway.

PMID- 29049994
TI  - Asia Pacific Stroke Conference 2017. Abstracts of the Annual Conference of the
      Asia Pacific Stroke Organization (APSO) Combined with Stroke Society of
      Australasia. Nanjing, China, October 26-28, 2017: Abstracts.

PMID- 29049993
TI  - Less Limb Muscle Involvement in Myositis Patients with Anti-Mitochondrial
      Antibodies.
AB  - Recent studies have revealed the clinical, histological, and pathophysiological
      characteristics in a group of inflammatory myopathies with selected
      autoantibodies. We retrospectively compared the clinical manifestations and
      histological features between 8 anti-mitochondrial (anti-M2) antibody-positive
      and 33 antibody-negative patients. Patients with anti-M2 antibodies have been
      previously reported to have delayed diagnostic confirmation and frequent
      cardiopulmonary complications in comparison to those without the antibodies. In
      our study, clinical characteristics in patients with the antibodies were as
      follows: lesser degree of limb muscle weakness and atrophy as well as lymphocytic
      infiltration in muscle biopsy specimens, and frequent paravertebral muscle
      atrophy. Anti-M2 antibody appeared to be a biomarker related to not only
      cardiopulmonary complications, but also characteristic -distributions of affected
      muscles.

PMID- 29049996
TI  - Nogo-B Promotes Angiogenesis in Proliferative Diabetic Retinopathy via
      VEGF/PI3K/Akt Pathway in an Autocrine Manner.
AB  - BACKGROUND/AIMS: Nogo-B, a conservative protein of endoplasmic reticulum, is a
      member of the reticulon family of proteins. Proliferative diabetic retinopathy
      (PDR) is the major concerning problem of diabetic retinopathy. This study
      explored the role of Nogo-B in the regulation of angiogenesis in PDR patients and
      primary human retinal endothelial cells (HRMECs). METHODS: Nogo-B was down
      regulated through the use of Lentivirus-NogoB-RNAi, the effects of Nogo-B on
      angiogenesis under high glucose stimulation were evaluated via CCK-8 assay, wound
      closure assay, transwell assay, and tube formation assay. Expression of Nogo-B,
      VEGF, PI3K and Akt were determined by western blotting, immunofluorescence,
      enzyme-linked immunosorbent assay (ELISA). Co-culture systerm was used to explore
      cell communication. RESULTS: Nogo-B was highly enriched in ocular tissues of PDR
      patients and in HRMECs exposed to high glucose. Down-regulation of Nogo-B
      attenuated high glucose induced cell migration and tube formation in HRMECs.
      Mechanistically, in comparison with the negative control group, Lentivirus-NogoB
      RNAi group had exhibited reduced VEGF secretion, weakened PI3K and Akt
      activation. Besides, high glucose treatment promoted the secretion of Nogo-B and
      presented as a "long-term memory". CONCLUSIONS: These data collectively indicated
      that Nogo-B promoted angiogenesis in HRMECs via VEGF/PI3K/Akt pathway in an
      autocrine manner.

PMID- 29049997
TI  - Discrepancies between Perceived and Measured Cognition in Kidney Transplant
      Recipients: Implications for Clinical Management.
AB  - BACKGROUND: Cognitive impairment is common in kidney transplant (KT) recipients
      and affects quality of life, graft survival, morbidity, and mortality. Failure to
      identify patients with cognitive impairment can withhold appropriate and timely
      intervention. This study determines whether measured cognition with standard
      screening tools offers any advantage over perceived cognition in screening
      transplant patients for cognitive impairment. METHODS: Cognition was assessed in
      157 KT recipients using the Montreal Cognitive Assessment (MoCA; measured
      cognition). In addition, transplant physicians and nurse coordinators were asked
      to rate transplant recipients' level of cognition after routine clinical
      interactions (perceived cognition). Physicians and nurses were blind to MoCA
      scores. Perceived cognition scores were compared to MoCA scores. RESULTS:
      Perceived cognition scores fairly correlated with MOCA scores (gamma = 0.24, p =
      0.001 for physicians and gamma = 0.33, p < 0.0001 for nurses). Physician scores
      moderately correlated with nurses scores (kappa = 0.44, p < 0.0001). Clinical
      perception had a low accuracy for identifying patients with cognitive impairment
      (sensitivity 66% for physicians, 65% for nurses), and those without cognitive
      impairment (specificity 67% for physicians, 76% for nurses). CONCLUSION: Clinical
      perception is inaccurate at detecting cognitive impairment in KT recipients.
      Objective tests should be considered to screen KT recipients for cognitive
      impairment.

PMID- 29049998
TI  - Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a
      Cisplatin-Induced Ototoxicity Rat Model.
AB  - Endoplasmic reticulum (ER) stress arises when excessive improperly folded
      proteins accumulate in the ER lumen. When ER stress occurs, the unfolded protein
      response (UPR) is subsequently activated to restore ER proteostasis. However,
      severe ER stress leads to apoptosis. Recent studies have suggested that cisplatin
      cytotoxicity may be related to ER stress. The purpose of this study was to
      determine whether ER stress participates in cochlear cell apoptosis in a
      cisplatin-induced ototoxicity rat model and to also determine the possible
      relationship between ER stress and hearing loss. Our results revealed that
      treatment with cisplatin upregulated the expression of active caspase-12 in
      cochlear cells, which is indicative of cisplatin-induced activation of ER
      specific apoptosis. Increased expression of C/EBP homologous protein (CHOP) and
      cleaved caspase-9 suggested a close relationship between severe ER stress and
      mitochondria-dependent apoptosis in the cochlear cells of cisplatin-treated rats.
      In addition, we found that tauroursodeoxycholic acid (TUDCA), a promoter of ER
      proteostasis, had a protective effect on cisplatin-induced hearing loss. These
      results demonstrate that ER stress is involved in the cisplatin-induced apoptosis
      of cochlear cells in vivo.

PMID- 29049999
TI  - Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular
      Carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most common primary liver
      malignancy and is a leading cause of cancer-related death worldwide. Luteolin, a
      flavonoid from traditional Chinese medicine, shows anti-cancer activity in many
      cancer cells, including HCC. However, the mechanism underlying the action of
      luteolin in HCC, especially its role in regulating cell autophagy, remains
      unclear. In the present study, we investigated the role of luteolin in regulating
      cell autophagy and the role of autophagy in luteolin-induced apoptosis. METHODS:
      The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) was
      used to investigate cell viability. Flow cytometry analysis was used to detect
      the cell cycle and cell apoptosis. Hoechst 33342 staining was used to detect cell
      apoptosis. Transmission electron microscopy was used to investigate autophagy.
      qRT-PCR and western blotting were used to detect apoptosis- and autophagy-related
      mRNAs and proteins. RESULTS: Luteolin reduced the viability of SMMC-7721 cells in
      a time and dose-dependent manner, and induced significant G0/G1-phase arrest. In
      addition, the results of flow cytometry analysis and Hoechst 33342 staining
      showed that luteolin treatment increased the number of apoptotic cells obviously,
      and the results of qRT-PCR and western blotting showed that luteolin treatment
      increased caspase 8 and decreased bcl-2 at the mRNA and protein levels.
      Furthermore, luteolin increased the number of intracellular autophagosomes,
      promoted LC3B-I conversion to LC3B-II, and increased Beclin 1 expression.
      Finally, co-treatment with the autophagy inhibitor chloroquine weakened the
      effects of luteolin on cell apoptosis. CONCLUSION: Luteolin induced apoptosis in
      human liver cancer SMMC-7721 cells, partially via autophagy. Thus, luteolin could
      be used as a regulator of autophagy in HCC treatment.

PMID- 29050000
TI  - Spinal Cord Injury Following Antegrade Scrotal Sclerotherapy for Varcicocele: A
      Case Report.
AB  - Varicocele is one of the causes of male infertility. Treatment aims to improve
      the chance of conception despite lasting controversies about benefits of
      varicocele repair on fertility. Many techniques have been described for
      varicocele management including the antegrade scrotal sclerotherapy (ASS).
      Interestingly, ASS is often presented as a safe, easy, and cost-effective
      procedure with low recurrence and complication rates. However, we report the
      first case of spinal cord paralysis following ASS probably due to embolization of
      venous anastomoses between left spermatic and ascending lumbar veins, which were
      undetected at preoperative phlebography. Based on this case and recent
      literature, we raise questions about the safety of ASS and try to figure out what
      would be the best way to improve the detectability of potential harmful
      anastomoses at preoperative phlebography.

PMID- 29050001
TI  - Expression of Angiogenic and Inflammatory Factors in Choroidal Neovascularisation
      Derived Retinal Pigment Epithelium.
AB  - PURPOSE: Anti-angiogenic treatment is well established in the management of
      exudative age-related macular degeneration (AMD), but not sufficient in all
      patients. The characterisation of factors driving this chronic disease could
      serve to identify additional treatment options. The purpose of this study was to
      assess gene expression patterns and distinct changes in cells derived from
      surgically extracted choroidal neovascularisation (CNV) membranes. MATERIALS AND
      METHODS: The expression of >11,000 genes was analysed by means of a microarray in
      cells cultured from 2 late-stage CNV membranes compared to primary human retinal
      pigment epithelium (RPE) and ARPE-19 cells. A pathway analysis was performed to
      identify gene expression patterns associated with exudative AMD. RESULTS: The
      analysis revealed significant alterations in gene sets associated with
      inflammatory processes in CNV-derived cells, involving the upregulation of pro
      inflammatory factors IL6, C3, and C5, and downregulation of anti-inflammatory
      complement factor B and complement factor I. Factors associated with
      angiogenesis, such as VEGFA or ANGPT2, were not significantly regulated in the 2
      RPE-derived cell lines. CONCLUSION: In late-stage CNV membrane-derived RPE, gene
      expression was shifted towards a pro-inflammatory state. Angiogenesis-associated
      factors were regulated differently in the 2 CNV-derived RPE membranes. While
      inflammation seems to be continuously stimulated by RPE associated with late
      exudative AMD, this appears not to be the case with regard to angioregulatory
      mechanisms.

PMID- 29050002
TI  - Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy.
AB  - Hematuria is one of the basic clinical manifestations of IgA nephropathy (IgAN).
      Isolated microscopic hematuria or microscopic hematuria combined with proteinuria
      is risk factor for the long-term prognosis of IgAN. Current evidence of the
      consequences of glomerular hematuria rests on insights from basic research on the
      molecular mechanisms of hemoglobin and related reactive oxygen species-induced
      tubular injury as well as on the clinical evidence of macroscopic hematuria
      associated acute kidney injury (AKI) in IgAN. These researches may simply
      elucidate some effects of macroscopic hematuria but not microscopic hematuria.
      Recent studies conducted on blood and urinary erythrocytes have made progress.
      Researches have revealed that mature erythrocytes contain abundant, long, non
      coding RNA, miRNA (microRNA) and Y RNA. Among the top 50 expressions of
      erythrocyte-derived miRNAs, 33 (66%) of them may be the potential urinary
      biomarkers of IgAN. Moreover, when urinary erythrocytes are compressed while
      exiting out of an impaired nephron, erythrocyte-derived vesicles (including
      microvesicles and apoptotic vesicles) may increase. Animal models for hematuria
      and human biopsy tissues confirm renal parenchymal cells could phagocytose red
      blood cells and erythrocyte-derived vesicles. These vesicles, which contain
      miRNAs, may alter the transcriptome of recipient cells and impact the occurrence
      and development of IgAN.

PMID- 29050003
TI  - Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by
      Suppressing Autophagy and Inducing Apoptosis in Vitro and in Vivo.
AB  - BACKGROUND/AIMS: Cantharidin, a type of terpenoid secreted by the blister beetle
      Mylabris phalerata (Pallas), has attracted great attention in cancer therapy
      because of its potential anti-cancer activities. Here, we report the effects on
      apoptosis and autophagy in human triple-negative breast cancer (TNBC) cell lines
      after treatment with cantharidin and attempt to elucidate the underlying
      mechanisms. METHODS: MDA-MB-231 and MDA-MB-468 cells were treated with
      cantharidin and cell proliferation was examined using CCK-8 and clone formation
      assays. The expression of apoptosis- and autophagy-associated proteins was
      detected by western blotting. Cells were infected with lentivirus carrying the
      Beclin-1 gene, and MDA-MB-231-beclin1 (MB231-Bec) and MDA-MB-468-beclin-1(MB468
      Bec) cells stably expressing Beclin-1 were established. Autophagic vacuoles in
      cells were observed with LC3 staining using fluorescence microscopy, and
      apoptotic cells were detected via flow cytometry. Tumor growth was assessed by
      subcutaneous inoculation of TNBC cells into BALB/c nude mice. RESULTS:
      Cantharidin inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells, and
      induced cell apoptosis. Cantharidin additionally inhibited the conversion of LC3
      I to LC3 II and autophagosome formation by suppressing the expression of Beclin
      1. Furthermore, overexpression of Beclin-1 in TNBC cells attenuated the
      cytotoxicity of cantharidin. In vivo, cantharidin inhibited the growth of MDA-MB
      231 and MDA-MB-468 xenografts in nude mice by suppressing autophagy and inducing
      apoptosis, and Beclin-1 overexpression in TNBC cells reduced the efficacy of
      cantharidin. CONCLUSIONS: Cantharidin inhibits autophagy by suppressing Beclin-1
      expression and inducing apoptosis of TNBC cells in vitro and in vivo, thereby
      representing a potential strategy for the treatment of TNBC.

PMID- 29050004
TI  - Study on Clinical Factors Involved in Helicobacter pylori-Uninfected,
      Undifferentiated-Type Early Gastric Cancer.
AB  - BACKGROUND: The factors associated with the pathogenesis of Helicobacter pylori
      uninfected undifferentiated-type early gastric cancer (HPUGC) remain unclear.
      This study compared patient characteristics, including medical history and
      alcohol/tobacco use, of HPUGC patients with characteristics of patients with H.
      pylori-positive undifferentiated-type early gastric cancer (HPPGC) to clarify and
      gain understanding on those differences that could play a role in the
      pathogenesis. METHODS: This retrospective study included 282 patients who were
      treated endoscopically from March 2005 to March 2014. This cohort consisted of
      232 patients with HPPGC (82.3%) and 50 patients with HPUGC (17.7%). Patient
      characteristics were analyzed by subgroups of HPUGC vs. HPPGC, with comparisons
      for age, gender, cancer history, comorbidity of lifestyle diseases requiring
      medication (hypertension, type 2 diabetes, and dyslipidemia), cumulative amount
      of alcohol consumption, and smoking history (Brinkman index [BI]). RESULTS: HPUGC
      patients were typically younger, had less frequent hypertension, and had higher
      BI values (p < 0.05 for all parameters). In a younger non-hypertensive subgroup,
      the OR for high BI (BI >=340) in the HPUGC group vs. HPPGC group was 5.049 (95%
      CI 2.458-10.373, p < 0.0001). CONCLUSIONS: The investigation of clinical factors
      identified smoking history as being possibly contributing to the pathogenesis of
      HPUGC. Future research is necessary at the cellular and genetic levels.

PMID- 29050005
TI  - Effect of Salt Intake on Serum Glucagon-Like Peptide-1 Levels in Normotensive
      Salt-Sensitive Subjects.
AB  - BACKGROUND/AIMS: Excess dietary salt is a critical risk factor of salt-sensitive
      hypertension. Glucagon-like peptide-1 (GLP-1) , a gut incretin hormone,
      conferring benefits for blood pressure by natriuresis and diuresis. We
      implemented a randomized trial to verify the effect of altered salt intake on
      serum GLP-1 level in human beings. METHODS: The 38 subjects were recruited from a
      rural community of Northern China. All subjects were sequentially maintained a
      baseline diet period for 3 days, a low-salt diet period for 7 days (3.0g/day of
      NaCl) , and a high-salt diet period for additional 7 days (18.0g/day of NaCl).
      RESULTS: Serum GLP-1 level increased significantly with the change from the
      baseline period to the low-salt diet period and decreased with the change from
      the low-salt to high-salt diet in normotensive salt-sensitive (SS) but not salt
      resistant (SR) individuals. There was a significant inverse correlation between
      the serum GLP-1 level and the MAP in SS subjects. Inverse correlation between the
      serum GLP-1 level and 24-h urinary sodium excretion was also found among
      different dietary interventions in SS subjects. CONCLUSIONS: Our study indicates
      that variations in dietary salt intake affect the serum GLP-1 level in
      normotensive salt-sensitive Chinese adults.

PMID- 29050006
TI  - Recent Insights into the Biological Functions of Sestrins in Health and Disease.
AB  - Sestrins (Sesns) have been identified as a family of highly conserved stress
      inducible proteins that are strongly up-regulated by various stresses, including
      DNA damage, oxidative stress, and hypoxia. The Sesns play protective roles in
      most physiological and pathological conditions mainly through the regulation of
      oxidative stress, inflammation, autophagy, endoplasmic reticulum stress, and
      metabolic homeostasis. In this review, we discussed the possible regulators of
      Sesns expression, such as p53, forkhead box O, nuclear factor erythroid 2 like 2
      (Nrf2), NH (2)-terminal kinase (JNK)/c-Jun pathway and hypoxia-inducible factor
      1alpha (Hif-1alpha), and the downstream pathways regulated by the Sesns including
      AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)
      signaling, mitogen-activated protein kinases (MAPKs) signaling, Nrf2 signaling,
      NADPH oxidase signaling and transforming growth factor beta (TGF-beta) signaling
      in heart diseases, lung diseases, gastrointestinal tract diseases, liver and
      metabolism diseases, neurological diseases, kidney diseases and immunological
      diseases. This review aims to provide a comprehensive understanding the
      protective effects of Sesns.

PMID- 29050007
TI  - Comparison of Safety and Efficacy of Tacrolimus versus Infliximab for Active
      Ulcerative Colitis.
AB  - BACKGROUND: This narrative review was to determine which medication, tacrolimus
      (TAC) or infliximab (IFX), is safer and more effective in the management of
      active UC. Our literature search identified 5 studies directly comparing the
      outcomes of TAC versus IFX for active UC. A review of the 5 studies was
      undertaken. SUMMARY: The incidence of serious adverse events was not
      significantly different between the TAC and IFX groups. The short-term clinical
      remission and response rates and the colectomy-free rates were similar between
      the groups. TAC was usually withdrawn at week 12 and, therefore, the long-term
      efficacy of TAC could not be properly evaluated. The majority of patients in the
      IFX group maintained clinical remission in the long-term. The efficacy of IFX as
      second-line salvage therapy after failure of TAC appeared to be favourable, but
      the efficacy of TAC after failure of IFX was questionable. Key Messages: Both TAC
      and IFX appeared to be equally safe and effective in the short-term for patients
      with active UC. For the moment, treatment choice, TAC or IFX, should be guided by
      physician and centre experience. Randomised controlled trials are urgently
      warranted to rigorously compare the efficacy of TAC versus IFX for active UC.

PMID- 29050009
TI  - Real-World Results of Intravitreal Ranibizumab, Bevacizumab, or Triamcinolone for
      Diabetic Macular Edema.
AB  - OBJECTIVE: To compare the visual and anatomical outcomes of intravitreal
      ranibizumab (group 1), bevacizumab (group 2), and triamcinolone (group 3) for
      center-involving diabetic macular edema. METHODS: We retrospectively enrolled 275
      eyes of 208 consecutive patients. Visual acuity (VA) in Early Treatment Diabetic
      Retinopathy Study (ETDRS) letters and central macular thickness (CMT) values on
      optical coherence tomography were extracted. Reported side effects were noted.
      RESULTS: At 6 months, the mean changes in VA in group 1, group 2, and group 3
      were +4.9, +4.3, and +4.6 letters, respectively (p = 0.911). Improvement of CMT
      at 6 and 24 months was significantly better in group 3 compared to groups 1 and 2
      (p = 0.012 and p = 0.001, respectively). At 24 months, the only independent
      variable affecting the change in VA was initial VA (p = 0.020). Cataract and
      glaucoma prevalences were higher in group 3 (p = 0.000 and p = 0.001,
      respectively). CONCLUSIONS: Three treatment methods had similar effects with
      regard to improvement in VA; however, intravitreal triamcinolone provided
      additional anatomical improvement.

PMID- 29050008
TI  - Response of the Endothelium to the Epicutaneous Application of Leukotriene B4.
AB  - BACKGROUND: Vascular changes, both endothelial and functional, are crucial events
      in inflammatory responses. OBJECTIVES: To investigate the dynamics of endothelial
      cell (EC) and functional changes during acute inflammation in an in vivo model of
      the skin using leukotriene B4. METHODS: EC proliferation, vascular network size,
      vessel diameter (VD), and hypoxia-inducible factor (HIF)-1alpha were studied by
      immunohistochemical CD31/Ki67 double staining and single staining of HIF-1alpha.
      Cutaneous perfusion (CP) was assessed using the Twente Optical Perfusion Camera.
      RESULTS: The initial phase illustrated an increase in VD, Ki67+ EC, and HIF
      1alpha expression and late-phase vascular expansion. The HIF-1alpha and Ki67+ EC
      expression was limited. CP and VD were augmented after 24 h. CONCLUSION: The
      early phase of inflammation is characterized by EC proliferation and HIF-1alpha
      expression. Vascular expansion continues over time. CP and VD are seen in both
      phases of inflammation. Angiogenesis, vascular network formation, and perfusion
      are time-dependent processes which are mutually related during inflammation.

PMID- 29050010
TI  - Calcium-Sensing Receptor Stimulation in Cultured Glomerular Podocytes Induces
      TRPC6-Dependent Calcium Entry and RhoA Activation.
AB  - BACKGROUND/AIMS: Recent studies provided compelling evidence that stimulation of
      the calcium sensing receptor (CaSR) exerts direct renoprotective action at the
      glomerular podocyte level. This protective action may be attributed to the RhoA
      dependent stabilization of the actin cytoskeleton. However, the underlying
      mechanisms remain unclear. METHODS: In the present study, an immortalized human
      podocyte cell line was used. Fluo-3 fluorescence was utilized to determine
      intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to
      measure canonical transient receptor potential 6 (TRPC6) protein expression and
      RhoA activity. Stress fibers were detected by FITC-phalloidin. RESULTS:
      Activating CaSR with a high extracellular Ca2+ concentration ([Ca2+]o) or R-568
      (a type II CaSR agonist) induces an increase in the [Ca2+]i in a dose-dependent
      manner. This increase in [Ca2+]i is phospholipase C (PLC)-dependent and is
      smaller in the absence of extracellular Ca2+ than in the presence of 0.5 mM
      [Ca2+]o. The CaSR activation-induced [Ca2+]i increase is attenuated by the
      pharmacological blockage of TRPC6 channels or siRNA targeting TRPC6. These data
      suggest that TRPC6 is involved in CaSR activation-induced Ca2+ influx. Consistent
      with a previous study, CaSR stimulation results in an increase in RhoA activity.
      However, the knockdown of TRPC6 significantly abolished the RhoA activity
      increase induced by CaSR stimulation, suggesting that TRPC6-dependent Ca2+ entry
      is required for RhoA activation. The activated RhoA is involved in the formation
      of stress fibers and focal adhesions in response to CaSR stimulation because
      siRNA targeting RhoA attenuated the increase in the stress fiber mediated by CaSR
      stimulation. Moreover, this effect of CaSR activation on the formation of stress
      fibers is also abolished by the knockdown of TRPC6. CONCLUSION: TRPC6 is involved
      in the regulation of stress fiber formation and focal adhesions via the RhoA
      pathway in response to CaSR activation. This may explain the direct protective
      action of CaSR agonists.

PMID- 29050011
TI  - Urine Ammonium, Metabolic Acidosis and Progression of Chronic Kidney Disease.
AB  - The metabolism of a typical Western diet generates 50-100 mEq of acid (H+) per
      day, which must be excreted in the urine for the systemic acid-base to remain in
      balance. The 2 major mechanisms that are responsible for the renal elimination of
      daily acid under normal conditions are ammonium (NH4+) excretion and titratable
      acidity. In the presence of systemic acidosis, ammonium excretion is intensified
      and becomes the crucial mechanism for the elimination of acid. The impairment in
      NH4+ excretion is therefore associated with reduced acid excretion, which causes
      excess accumulation of acid in the body and consequently results in metabolic
      acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid
      excretion and precipitation of metabolic acidosis, which has an adverse effect on
      the progression of CKD. Recent studies suggest that the progressive decline in
      renal ammonium excretion in CKD is an important determinant of the ensuing
      systemic metabolic acidosis and is an independent factor for predicting the
      worsening of kidney function. While these studies have been primarily performed
      in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in
      non-hypertensive individuals with CKD is warranted to ascertain its role in the
      progression of kidney disease.

PMID- 29050012
TI  - Mission Statement.

PMID- 29050013
TI  - Persistent Full-Thickness Idiopathic Macular Hole: Anatomical and Functional
      Outcome of Revitrectomy with Autologous Platelet Concentrate or Autologous Whole
      Blood.
AB  - PURPOSE: To evaluate long-term outcome after revitrectomy with autologous
      platelet concentrate (APC) or whole blood (WB) in persistent idiopathic macular
      hole (MH) after vitrectomy with internal limiting membrane (ILM) peeling.
      PROCEDURES: Retrospective study of 75 eyes with persistent MH after vitrectomy
      with ILM peeling and gas. All patients underwent revitrectomy with gas and APC (n
      = 61) or WB (n = 14). Main outcome measures were anatomical closure rate and
      postoperative best-corrected visual acuity (BCVA). RESULTS: Closure rate after
      revitrectomy was 85.2% (52/61) in the APC group and 7.1% (1/14) in the WB group.
      Median follow-up was 58 (range 3-147) months. Median BCVA (logMAR) in patients
      with finally closed MHs was 0.4 +/- 0.3. Patients with defects of the ellipsoid
      zone had significantly worse postoperative BCVA. Morphological MH configuration
      (atrophic or elevated edges) did not correlate with final closure rate.
      CONCLUSIONS: Revitrectomy with APC and gas is a very effective treatment in
      persistent MH after vitrectomy with ILM peeling and gas.

PMID- 29050014
TI  - A Real-Life Analysis of Reproductive Outcome after Fertility Preservation in
      Female Cancer Patients.
AB  - BACKGROUND: Fertility preservation before or during cancer treatment in young
      women has become an important health issue because of delayed motherhood and
      improved survival rates. This study evaluates the necessity and the efficacy of
      fertility preservation, with a focus on actual pregnancy wish and outcome after
      fertility preservation and cancer treatment. PATIENTS AND METHODS: All
      consecutive patients who received fertility preservation in 2 university referral
      centers before or during cancer treatment were included. After a minimal follow
      up of 3 years, pregnancy wish, pregnancy attempts and fertility outcome were
      assessed during a dedicated consultation or during a telephone interview.
      RESULTS: A total of 159 patients received fertility preservation including
      hormonal protection with gonadotropin-releasing hormone agonist (n = 93, 58.5%),
      ovarian tissue cryopreservation (n = 44, 27.7%), and combined hormonal protection
      and ovarian tissue cryopreservation (n = 22, 13.8%). Among the 91 (57.2%)
      patients in remission after a mean follow-up of 61.5 months, 29 (31.9%) women
      actively attempted pregnancy. Patients who had received ovarian cryopreservation
      were more likely to attempt pregnancy (18/66) than those who only received
      hormonal protection (11/93, p = 0.02). Out of the 29 women who attempted
      pregnancy, 16 (55.2%) became pregnant, and most of them conceived spontaneously
      (87.5%, 14/16). Out of the 13 women who did not become pregnant, 1 patient
      adopted a child and 12 patients still wanted to become pregnant, including 1
      patient who underwent a transplantation of her cryopreserved ovarian tissue
      without success. CONCLUSION: In one of the first studies reporting real-life
      experience in centers for fertility preservation, we found that, within 5 years
      following the end of cancer treatment, only one third of patients in remission
      attempted to become pregnant, with a pregnancy rate of 55%, mostly after
      spontaneous conception.

PMID- 29050015
TI  - Incidence, Prevalence and Global Distribution of Root Caries.
AB  - High quality epidemiological data are essential for both the development of
      national oral health policies and cost-effective targeting of resources.
      Unfortunately, a high level of clinical heterogeneity between studies in this
      area makes it difficult, and inappropriate, to try to produce any definitive
      figures on the global prevalence or incidence of root caries. Published studies
      have reported wide ranges for the prevalence of root caries (25-100%) and the
      mean Root Caries Index (9.7-38.7). The reported range for annual root caries
      incidence is also wide, from 10.1 to 40.6%. While more research is needed in this
      area, most studies conclude that the burden of root caries is high in the older
      age population.

PMID- 29050016
TI  - Etiology, Risk Factors and Groups of Risk.
AB  - Population aging and the concomitant reduction in tooth loss will have a profound
      effect on dentistry. In particular, an increase in the prevalence of root caries
      can be expected. Root caries is not evenly distributed across the population and
      identification of high-risk groups or individuals would facilitate targeted
      prevention strategies. Unfortunately, the lack of consensus in the literature on
      the diagnosis and measurement of root caries makes comparison of studies
      extremely challenging. At present, we do not have an adequately validated risk
      assessment tool for root caries. Future research should focus resources on
      investigating risk indicators, which have been found to be significant in past
      studies and on externally validating previously described risk models.

PMID- 29050017
TI  - Specificities of Caries on Root Surface.
AB  - Variations in organic and inorganic composition and morphology may determine
      different susceptibilities of root surfaces to caries. Subsequent to gingival
      recession, root surfaces become exposed and those areas where Sharpey's fibers
      system was once inserted into the cementum are converted into canals for
      microbial penetration. In the presence of a cariogenic root biofilm, the
      fermentable carbohydrate from diet is converted into organic acid, and the root
      caries lesion is initiated in the exposed root site. We will revisit here the
      structural, biochemical, and histopathological specificities of root caries.
      Likewise enamel, the root surface exchange minerals with oral fluids, resulting
      in a subsuperficial root caries lesion. After mineral loss, the collagen is
      degraded and the lesion progresses. The specificities regarding the critical pH
      for demineralization of root hard tissues, the influence of cementum loss for
      lesion progression, and the organic matrix degradation will be discussed in this
      chapter. The tissue-related phenomena would create lesion with a unique
      histopathology. Active and arrested root carious lesions will be discussed
      through the gradual development from the cementum to dentin.

PMID- 29050018
TI  - Root Surface Biofilms and Caries.
AB  - Following gingival recession, which increases with age, the root surface becomes
      exposed, creating new environments for microbial colonization and biofilm
      formation. The formation of root surface biofilms is influenced by the
      availability and composition of saliva and gingival crevicular fluid; they
      provide components for the conditioning film (acquired root surface pellicle) and
      also act as a source of nutrients. The early bacterial colonizers of the root
      surface are similar to those found on the enamel, and Gram-positive species such
      as Streptococcus sanguinis, S. oralis, S. mitis, and Actinomyces species
      predominate. The root surface has a lower mineral and higher organic content than
      enamel, and so is more vulnerable to demineralization. The characterization of
      the microbiota associated with root surface lesions is still ongoing. Traditional
      culture-based studies have implicated species such as mutans streptococci,
      lactobacilli, bifidobacteria, and Actinomyces species, while molecular-based
      studies have provided evidence for a more complex microbiota with many Gram
      negative and anaerobic bacteria being detected in addition to the more
      conventional cariogenic organisms. Ecological concepts have been applied to
      explain the microbial etiology of root caries. The acidic environment generated
      from the fermentation of dietary sugars selects saccharolytic bacteria that can
      preferentially grow and metabolize under low pH conditions, and then proteolytic
      Gram-negative species are selected when the dentin is exposed and collagen and
      other proteins become accessible to be catabolized. These species act in concert
      to degrade the inorganic and organic components of the dental tissues.

PMID- 29050019
TI  - Endogenous Enzymes in Root Caries.
AB  - Similar to coronal caries, root caries results from a disequilibrium of the de
      remineralization balance in favor of the demineralization process. It mainly
      involves a bacterial shift in favor of an increase in the proportion of
      acidogenic and aciduric bacteria. This process permanently damages the dental
      mineralized tissues, namely the dental cementum and dentin. In addition to the
      demineralization and exposure of the dentin or the cementum organic matrix, acid
      production by cariogenic bacteria induces the activation of endogenous (host
      derived) enzymes within the dentin and saliva. These enzymes include matrix
      metalloproteinases and cathepsins. Once activated, these potent proteolytic
      enzymes collectively have the capacity to degrade all the components of the
      exposed organic dentin and cementum matrices. In this chapter, the description of
      the healthy cement and dentin organic matrices and their endogenous proteases
      will be followed by the role of these proteases in the root caries process.

PMID- 29050020
TI  - Root Surface Caries - Rationale Behind Good Diagnostic Practice.
AB  - Root surfaces, which with increasing age become exposed to dental biofilms, will
      react to the intermittent pH fluctuations at the interface between the biofilm
      and the cementum/dentin surface. If dental biofilm is left undisturbed in
      stagnation sites in the dentition, the underlying mineral surfaces may gradually
      develop dental caries characterized by a subsurface loss of mineral. In root
      surfaces, the demineralization is accompanied by microbial invasion of the
      cementum and dentin resulting in a pulpo-dentinal defense reaction. Most lesions
      progress slowly and experimental in situ studies as well as clinical studies
      document that the daily removal of the biofilm using fluoride toothpaste can
      arrest lesion progression. By applying this caries control measure, caries
      lesions can thus be transformed from active lesions to inactive lesions. The
      diagnostic characteristics of these types of lesions are mandatory to apply in
      daily clinical practice to avoid unnecessary restorative and antimicrobial
      treatments.

PMID- 29050021
TI  - Assessing the Risk of Developing Carious Lesions in Root Surfaces.
AB  - Patients' susceptibility to coronal and root caries (RC) is modulated by a range
      of biological, environmental, social, psychological, and behavior-related
      factors. These factors, considered either in isolation or combined into specific
      models, contribute to the overall patient susceptibility/risk of new lesion
      occurrence and/or of existing lesion progression, allowing the oral healthcare
      team to define specific and individualized preventive and curative regimens.
      Various caries susceptibility/risk assessment (CRA) protocols/models have been
      developed to assist the oral healthcare practitioner/team in a logical systematic
      approach to synthesize information about the caries disease process with its
      multifactorial etiology. These protocols/models consider caries
      susceptibility/risk in general without any specific localization of the caries
      process; none of them specifically consider the risk of developing carious
      lesions in root surfaces. This chapter aims to discuss CRA related to RC lesions
      in terms of prediction of both the occurrence of new RC lesions and of continuing
      progression of existing lesions.

PMID- 29050022
TI  - Assessment of Root Caries Lesion Activity and Its Histopathological Features.
AB  - Despite certain similarities in the etiology of root caries (RC) and coronal
      caries, there are notable differences in their histology, namely with regard to
      the demineralization process, which should be taken into consideration when
      assessing lesion activity. In this chapter, we present the histological changes
      to the dentin and pulp, occurring physiologically or in response to caries
      lesions. We focus on the histological features specific to RC lesions, discussing
      the assessment of lesion activity. The physiological changes occurring to the
      dentin and pulp are the formation of secondary dentin and the sclerosis of dentin
      tubules, while tertiary dentin is formed during pathologic stimuli from caries
      lesions. Already in the early stages of active RC, the lesions seem softer, and
      bacteria are easily found within the dentin tubules. Inactive lesions, on the
      contrary, are characterized by fully remineralized tissue, with irregular mineral
      precipitation and containing ghost cells of microorganisms. Lesion activity is
      determined by observing their tactile sensation and their position with respect
      to the gingival margin.

PMID- 29050023
TI  - Monitoring of Root Caries Lesions.
AB  - The early detection of root caries is essential for the implementation of
      appropriate preventive therapeutic regimes. Subsequent monitoring of lesions is
      required to determine the outcomes of such therapies. While much research
      activity has been seen in the detection and monitoring of enamel caries, this has
      not been seen in root caries - despite the possibilities for shorter clinical
      trials due to the more rapid remineralization and arrest of such lesions. The
      main stay of both clinical practice and research has been the use of visual
      tactile criteria including, hardness, texture, the presence or absence of
      cavitation, and color. A range of clinical trials, using high fluoride products
      of known efficacy, have shown such techniques to be valid. The use of adjunct
      technologies has been limited in large scale in vivo studies, to devices using
      electrical resistance measurement (electronic caries monitor, ECM). The use of
      dyes, laser fluorescence, and advanced imaging such as near infra-red has been
      described in vitro but few, with the exception of DiagnoDent, have been
      translated to chair side. Except for ECM, no other technology has been used in
      the clinical assessments of root caries remineralization and there remains a need
      to supplement visual tactile techniques for future work.

PMID- 29050024
TI  - Biofilm Control and Oral Hygiene Practices.
AB  - As the thick biofilm in the presence of fermentable carbohydrates is the main
      etiological factor of dental caries, the frequent and systematic removal of this
      colony by means of an effective biofilm control should result in the prevention
      of caries lesions or in the arrest of the local carious process. However, the
      role of biofilm control in the management of dental caries has been questioned.
      This chapter will discuss the biofilm control and oral hygiene practices on root
      surfaces. Laboratory and clinical studies describing the effect of biofilm
      control and oral hygiene practices on the arrestment of root carious lesions are
      described. Epidemiological surveys evaluating the association between oral
      hygiene and root caries are discussed. Finally, some aspects on chemical biofilm
      control are also presented.

PMID- 29050025
TI  - Conventional Preventive Therapies (Fluoride) on Root Caries Lesions.
AB  - Root caries lesions (RCLs) are highly prevalent in elderly and can negatively
      impact the quality of life. Therefore, preventive therapies should be applied to
      control or to arrest RCLs. This chapter will discuss the application of fluoride,
      a conventional preventive therapy, to control RCLs. Among the self-applied
      products, there is strong evidence that 5,000 ppm F toothpaste is more effective
      in arresting RCLs (by increasing hardness) and in preventing new lesions (PF of
      51%) compared to 1,100-1,450 ppm F toothpastes, in 6-month clinical trials. With
      regard to professional fluoride applications, 5% NaF varnish (4 times/year) and
      38% silver diamine fluoride solution (1 time/year) have been tested in clinical
      trials with a follow-up of 3 years. Five percent NaF varnish and 38% silver
      diamine fluoride have been shown to prevent the emergence of new RCLs in 64 and
      71%, respectively. The professional fluoride application is often combined with
      the daily use of 5,000 ppm F toothpaste. However, there is a gap in the knowledge
      about the benefit (cost-effectiveness) and the optimal use of the combinations of
      fluoride products in the control of RCLs.

PMID- 29050026
TI  - New Preventive Approaches Part I: Functional Peptides and Other Therapies to
      Prevent Tooth Demineralization.
AB  - The limited effect of fluoride on root caries has prompted the study of new
      preventive therapies, which involve recently developed functional peptides,
      lasers, phosphate-based technologies, among several other approaches. Most of the
      specific peptides currently investigated have been developed based on the
      available information related to the protective action of salivary proteins,
      including statherin-derived peptides. Other peptides include 8DSS, self
      assembling peptide P11-4, antimicrobial peptides, and casein phosphopeptides
      combined with amorphous calcium phosphate. These were shown to increase
      remineralization and/or to protect against demineralization through different
      mechanisms, including the attraction of calcium ions to the demineralized tissue,
      delivery of available calcium, and antimicrobial action. Regarding phosphate
      based technologies, the addition of polyphosphate salts to fluoridated vehicles
      has been shown to promote a synergistic effect in promoting enamel
      remineralization and in preventing demineralization, in studies with in vitro, in
      situ, and clinical protocols. Sodium trimetaphosphate has also been shown to
      promote intrafibrillar collagen remineralization, phosphate uptake by previously
      demineralized dentin, and deposition of needle-like crystallites at
      intrafibrillar level. As for the use of lasers, their effects on the mineral
      content and crystallinity of dentin were shown to be related to the removal of
      water and protein, besides surface melting by thermal degradation. Lasers have
      also been shown to have synergistic/additive effects with fluoride on the
      prevention of root dentin demineralization, due to the enhanced fluoride uptake
      and the decreased calcium and phosphate loss. Although the above-mentioned
      therapies seem to be promising alternatives to prevent root caries, clinical
      evidence is still required.

PMID- 29050027
TI  - New Preventive Approaches Part II: Role of Dentin Biomodifiers in Caries
      Progression.
AB  - Dental caries is the most prevalent infectious chronic disease in children and
      adults. With a globally aging population, new demands in the management of dental
      caries are awakened by the rampant increase in the incidence of dental root
      caries. Like crown caries, root caries requires bacterial driven tissue
      demineralization followed by the degradation of the extracellular dentin matrix.
      Due to the complex composition and ultrastructure, preventive strategies
      targeting the mineral phase of dentin are insufficient for managing the
      prevention and progression of root caries. However, the composition and
      ultrastructure of dentin has inspired novel strategies for the effective
      management of highly susceptible root surfaces. Specifically, the complex and
      dynamic dentin extracellular matrix (ECM). The ECM of mature dentin contains a
      robust type I collagen fibrils scaffold, and carefully distributed non
      collagenous components, such as proteoglycans, phosphoproteins, and proteases. In
      this chapter, we will review the experimental strategies of potential clinical
      impact to prevent root caries progression by site modifications of the mature
      extracellular dentin matrix. This approach, termed dentin biomodification,
      encompasses bioinspired strategies to locally enhance the biological and
      biomechanical characteristics of the tissue by mimicking natural processes. Here,
      synthetic and biosynthetic compounds can decrease the biodegradability of the
      dentin ECM and provide mechanical enhancement of dentin. The resulting effect is
      the maintenance of the dentin ECM to halt root caries progression and possibly
      mediate effective remineralization of the caries affected root dentin.

PMID- 29050028
TI  - Management of Cavitated Root Caries Lesions: Minimum Intervention and
      Alternatives.
AB  - The prevalence of root caries among the elderly is increasing. The lesion shape
      can vary considerably from a broad shallow saucer-shape to a deeper defined
      cavity. The variety of shapes poses a series of complications when considering
      restorative management. This is accompanied with a paucity of clinical evidence
      on treatment techniques and clinical outcomes. The current philosophy centered on
      conservative management of root caries will most likely provide patients with the
      greatest chance of maintaining their teeth. When a lesion can be effectively
      cleaned in conjunction with a high fluoride content toothpaste and other
      remineralizing agents, this should be the treatment of choice. For lesions that
      are cavitated and cannot be effectively cleaned, the initial management should be
      to apply remineralizing agents for a period to "harden" lesion margins thus
      potentially reducing the prepared cavity and restoration size, as well as
      providing a better-defined tooth-restoration margin for finishing. Material
      selection is either a glass ionomer cement (conventional or resin-modified) or
      resin-based material. Frequently, the restoration site is easily contaminated;
      hence, glass ionomer cement is an ideal material. However, for saliva-deficient
      patients, resin composite or a combination of resin composite and resin-modified
      glass ionomer adhesive allows for a highly polished, easily cleansable
      restoration surface that may reduce the potential for further caries initiation.
      The current evidence base for the restoration of root caries is poor.

PMID- 29050029
TI  - Clinical Performance of Root Surface Restorations.
AB  - This chapter describes the clinical performance of restorations placed in root
      caries lesions. The prevalence of root caries and other types of cervical
      lesions, caused by abfraction, erosion, and abrasion (non-carious cervical
      lesions) are high, mainly in the elderly; and therefore, restorative procedures
      are indicated. We will revise the restorative materials used to restore these
      types of lesions and present evidence-based findings to provide clinicians with
      better evidence for choosing them. Additionally, some steps of the restorative
      procedure for the placement of resin-based composites will be revised and common
      clinical questions related to these steps will be answered based on high evidence
      level, produced by randomized clinical trials and systematic reviews of the
      literature.

PMID- 29050030
TI  - Concluding Remarks.
AB  - Case reports and clinical trials conducted in different countries (i.e., the
      United States, Canada, Brazil, Germany, Finland, Sweden, Japan, India, and Sri
      Lanka) tend to find a positive relationship between the presence of more retained
      teeth in older ages and the prevalence of root caries in older adults. As this
      tendency has been shown to prevail globally, it is estimated that the predicted
      demographic elderly expansion may cause, in near future, a significant increment
      in the number of older population requiring an effective means of preventing and
      treating root surface caries. Based on these concerns, the editors of the series
      Monographs in Oral Science by Karger Publishers, Dr. Adrian Lussi and Dr. Marilia
      Buzalaf, have invited me to organize a book, in which it was reunited a team of
      experts who could provide a critical and comprehensive understanding on the
      different aspects concurring for the caries phenomenon development on dental root
      surfaces. This team effort turned into a superb publication; the different parts
      of the book are indeed at the top level. Collectively, the chapters of this book
      brought a wide picture of the state-of-the-art in the addressed themes, which in
      turn will hopefully serve as a reference for readers and encourage new researches
      in the area.

PMID- 29050031
TI  - Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney.
AB  - While substantial information is available on organ anlage and the primary
      formation of nephrons, molecular mechanisms acting during the late development of
      the human kidney have received an astonishing lack of attention. In healthy
      newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery,
      morphogenetic activity in the nephrogenic zone decreases, and the stem cell
      niches aligned beyond the organ capsule vanish by an unknown signal. However,
      this signal also plays a key role in preterm and low birth weight babies.
      Although they are born in a phase of active nephrogenesis, pathological findings
      illustrate that they evolve to a high incidence oligonephropathy and prematurity
      of renal parenchyma. Different extra- and intrauterine influences seem to be
      responsible, but independent from chemical nature, all of them culminate in the
      nephrogenic zone. One assumes that the marred development is caused either by an
      overshoot of metabolites, misleading signaling of morphogens, unbalanced
      synthesis of extracellular matrix or restricted contact between mesenchymal and
      epithelial stem cells. Even more surprising is that there is only a few vague
      morphological information of the nephrogenic zone in the human fetal kidney
      available and ultrastructural data is severely lacking. On this account, the
      first coordinates were determined by optical microscopy and morphometry. Without
      claiming to be complete, generated results made it possible to create schematic
      illustrations true to scale for orientation. It will help graduating students,
      young pediatricians, pathologists, and scientists working in the field of
      biomedicine to interpret professionally the nephrogenic zone and contained
      niches.

PMID- 29050032
TI  - Providing Personalised Nutrition: Consumers' Trust and Preferences Regarding
      Sources of Information, Service Providers and Regulators, and Communication
      Channels.
AB  - BACKGROUND/AIMS: Personalised nutrition has potential to revolutionise dietary
      health promotion if accepted by the general public. We studied trust and
      preferences regarding personalised nutrition services, how they influence
      intention to adopt these services, and cultural and social differences therein.
      METHODS: A total of 9,381 participants were quota-sampled to be representative of
      each of 9 EU countries (Germany, Greece, Ireland, Poland, Portugal, Spain, the
      Netherlands, the UK, and Norway) and surveyed by a questionnaire assessing their
      intention to adopt personalised nutrition, trust in service regulators and
      information sources, and preferences for service providers and information
      channels. RESULTS: Trust and preferences significantly predicted intention to
      adopt personalised nutrition. Higher trust in the local department of health care
      was associated with lower intention to adopt personalised nutrition. General
      practitioners were the most trusted of service regulators, except in Portugal,
      where consumer organisations and universities were most trusted. In all
      countries, family doctors were the most trusted information providers. Trust in
      the National Health Service as service regulator and information source showed
      high variability across countries. Despite its highest variability across
      countries, personal meeting was the preferred communication channel, except in
      Spain, where an automated internet service was preferred. General practitioners
      were the preferred service providers, except in Poland, where dietitians and
      nutritionists were preferred. The preference for dietitians and nutritionists as
      service providers highly varied across countries. CONCLUSION: These results may
      assist in informing local initiatives to encourage acceptance and adoption of
      country-specific tailored personalised nutrition services, therefore benefiting
      individual and public health.

PMID- 29050033
TI  - Expert Panel Statement on Laparoscopic Living Donor Hepatectomy.
AB  - BACKGROUND: With improvements in living donor liver transplantation (LDLT)
      techniques and the increased experience of surgeons in laparoscopic major liver
      resection, laparoscopic donor hepatectomy is performed increasingly. Therefore,
      expert opinion on this procedure is required. OBJECTIVE: The study aimed to
      report the current status and summarize the expert opinion on laparoscopic donor
      hepatectomy. METHODS: An expert consensus meeting was held on September 8, 2016,
      in Seoul, Korea. RESULTS: Laparoscopic donor left lateral sectionectomy could be
      considered the standard practice in pediatric LDLT. In adult LDLT, laparoscopy
      assisted donor hepatectomy or left hepatectomy is potentially the next need,
      requiring more evidence for becoming standard practice. Laparoscopic donor right
      hepatectomy is still in the developmental stage, and more supporting evidence is
      required. Waving the cost consideration, the robotic approach could be a valid
      alternative for the suitable approaches of laparoscopy. CONCLUSIONS: Laparoscopic
      donor hepatectomy is increasing its role in both pediatric and adult LDLT.
      However, for major donor hepatectomy, more evidence is needed.

PMID- 29050034
TI  - Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells.
AB  - BACKGROUND: Metabolic abnormalities are frequently observed in multiple
      malignancies including epithelial ovarian cancer (EOC), among which imbalance
      between generation and elimination of reactive oxygen species (ROS) plays a
      critical role in EOC onset and progression. Here we investigated the role of miR
      29b, a well-established tumor-suppressor miRNA in metabolic regulation of EOC
      cells. METHODS: cell viability and apoptosis in miR-29b inhibited and over
      expressed EOC cells were evaluated by CCK8 and Annexin V-FITC/PI assays. Change
      in miR-29b was detected in EOC cells incubated in H2O2 culture by q-PCR. Relative
      ROS levels were also detected in different EOC cultures, including modified miR
      29b and SIRT1 levels as well as H2O2 incubation. A luciferase reporter assay was
      employed to detect the direct binding of miR-29b to SIRT1 3' UTR. Changes in cell
      viability and ROS levels were assessed in SIRT1-knocked down EOC cells. RESULTS:
      miR-29b expression correlates with decreased EOC cell viability and increased
      apoptosis. H2O2 downregulated miR-29b in a time and dose-dependent manner. miR
      29b expression negatively correlated with ROS levels, whereas SIRT1 significantly
      stimulated ROS formation. Luciferase reporter assays confirmed miR-29b
      downregulation of SIRT1by directly targeting its mRNA 3'-UTR. SIRT1 silencing
      rescues cell viability of H2O2 treated cells. Also, SIRT1 inhibition blocked cell
      apoptosis induced by H2O2 as well as reduced intracellular ROS levels.
      CONCLUSION: Together, our findings indicated that the miR-29b/SIRT1 axis has a
      protective effect against H2O2-induced damage of cell viability and oxidative
      stress and may provide novel options for miR-29b-based therapeutic approaches for
      EOC treatment.

PMID- 29050039
TI  - Cardiac Autonomic Dysfunction in Offspring of Hypertensive Parents During
      Exercise.
AB  - Offspring of hypertensive parents present autonomic dysfunction at rest and
      during physiological maneuvers. However, the cardiac autonomic modulation during
      exercise remains unknown. This study tested whether the cardiac autonomic
      modulation would be reduced in offspring of hypertensive parents during exercise.
      Fourteen offspring of hypertensive and 14 offspring of normotensive individuals
      were evaluated. The groups were matched by age (24.5+/-1.0 vs. 26.6+/-1.5 years;
      p=0.25) and BMI (22.8+/-0.6 vs. 24.2+/-1.0 kg/m2; p=0.30). Blood pressure and
      heart rate were assessed simultaneously during 3 min at baseline followed by 3
      min isometric handgrip at 30% of maximal voluntary contraction. Cardiac autonomic
      modulation was evaluated using heart rate variability. Primary variables were
      subjected to two-way ANOVA (group vs. time). P value<0.05 was considered
      statistically significant. Blood pressure and heart rate were similar between
      groups during exercise protocol. In contrast, offspring of hypertensive subjects
      showed a reduction of SDNN (Basal=34.8+/-3.5 vs. 45.2+/-3.7 ms; Exercise=30.8+/
      3.3 vs. 41.5+/-3.9 ms; p group=0.01), RMSSD (Basal=37.1+/-3.7 vs. 52.0+/-6.0 ms;
      Exercise=28.6+/-3.4 vs. 41.9+/-5.3 ms; p group=0.02) and pNN50 (Basal=15.7+/-4.0
      vs. 29.5+/-5.5%; Exercise=7.7+/-2.4 vs. 18.0+/-4.3%; p group=0.03) during the
      exercise protocol in comparison with offspring of normotensive parents. We
      concluded that normotensive offspring of hypertensive parents exhibit impaired
      cardiac autonomic modulation during exercise.

PMID- 29050040
TI  - Maximal Fat Oxidation is Related to Performance in an Ironman Triathlon.
AB  - The aim of the present study was to investigate the relationship between maximal
      fat oxidation rate (MFO) measured during a progressive exercise test on a cycle
      ergometer and ultra-endurance performance. 61 male ironman athletes (age: 35+/-1
      yrs. [23-47 yrs.], with a BMI of 23.6+/-0.3 kg/m2 [20.0-30.1 kg/m2], a body fat
      percentage of 16.7+/-0.7% [8.4-30.7%] and a VO2peak of 58.7+/-0.7 ml/min/kg [43.9
      72.5 ml/min/kg] SEM [Range]) were tested in the laboratory between 25 and 4 days
      prior to the ultra-endurance event, 2016 Ironman Copenhagen. Simple bivariate
      analyses revealed significant negative correlations between race time and MFO
      (r2=0.12, p<0.005) and VO2peak (r2=0.45, p<0.0001) and a positive correlation
      between race time and body fat percentage (r2=0.27, p<0.0001). MFO and VO2peak
      were not correlated. When the significant variables from the bivariate regression
      analyses were entered into the multiple regression models, VO2peak and MFO
      together explained 50% of the variation observed in race time among the 61
      Ironman athletes (adj R2=0.50, p<0.001). These results suggests that maximal fat
      oxidation rate exert an independent influence on ultra-endurance performance (>9
      h). Furthermore, we demonstrate that 50% of the variation in Ironman triathlon
      race time can be explained by peak oxygen uptake and maximal fat oxidation.

PMID- 29050041
TI  - Lower Limb Force, Velocity, Power Capabilities during Leg Press and Squat
      Movements.
AB  - The aim was to compare lower-limb power, force, and velocity capabilities between
      squat and leg press movements. Ten healthy sportsmen performed ballistic lower
      limb push-offs against 5-to-12 different loads during both the squat and leg
      press. Individual linear force-velocity and polynomial power-velocity
      relationships were determined for both movements from push-off mean force and
      velocity measured continuously with a pressure sensor and linear encoder. Maximal
      power output, theoretical maximal force and velocity, force-velocity profile and
      optimal velocity were computed. During the squat, maximal power output (17.7+/
      3.59 vs. 10.9+/-1.39 W.kg-1), theoretical maximal velocity (1.66+/-0.29 vs.
      0.88+/-0.18 m.s-1), optimal velocity (0.839+/-0.144 vs. 0.465+/-0.107 m.s-1), and
      force-velocity profile (-27.2+/-8.5 vs. -64.3+/-29.5 N.s.m-1.kg-1) values were
      significantly higher than during the leg press (p=0.000, effect size=1.72-3.23),
      whereas theoretical maximal force values (43.1+/-8.6 vs. 51.9+/-14.0 N.kg-1,
      p=0.034, effect size=0.75) were significantly lower. The mechanical capabilities
      of the lower-limb extensors were different in the squat compared with the leg
      press with higher maximal power due to much higher velocity capabilities (e.g.
      ability to produce force at high velocities) even if moderately lower maximal
      force qualities.

PMID- 29050042
TI  - [Therapy of Spondylodiscitis by Severity].
AB  - Spondylodiscitis is a rare but serious infection of the spine. Recognised methods
      of treatment include immobilisation and systemic antibiotics. However, available
      data for specific and recommendations for continuing treatment are also rare. The
      aim of the present study is the optimisation of the therapy of spondylodiscitis
      using a clinical pathway that depends on a classification of spondylodiscitis.
      From 1 October 1998 to 31 December 2013, a classification of the severity of
      spondylodiscitis was established, including specific treatment recommendations.
      As part of the re-evaluation, the classification of severity was adapted. On this
      basis, electronically based clinical pathways were developed. A total of 296
      cases were included. With a steadily increasing number of treatments, the mean
      age of the patients increased to 67.3 years. In 34.3% of these patients,
      spondylodiscitis developed spontaneously and 68.6% of patients did not receive
      treatment until the diagnosis. In the context of the specific treatment, pain
      intensity decreased from 6.0 to 3.1 NRS (numeric rating scale). The inflammatory
      values (CRP) decreased from 119.2 to 46.7 mg/dl. The time from the onset of
      symptoms to the surgical treatment was almost 65.6 days and has not changed
      significantly. Nevertheless, the time from admission to surgical treatment could
      be reduced to less than 3 days. The classification of patients into 3 degrees of
      severity of spondylodiscitis (SSC) depends on the SponDT: spondylodiscitis
      diagnosis and treatment. The SponDT describes vertebral destruction and the
      current neurological status. The severity-adapted therapy was mapped
      electronically and includes specific surgical care, systemic antibiotic therapy
      and physical therapy.

PMID- 29050044
TI  - ?

PMID- 29050045
TI  - ?

PMID- 29050043
TI  - [Malpractice Claims Against Pediatricians - Analysis of Expert Testimonies from
      the Medical Service of Health Insurance Companies Between 2000 and 2014].
AB  - Background In Germany, few data are available on medical malpractice claims
      against pediatricians. On behalf of Statutory Health Insurance Companies their
      Medical Service (MDK) regularly offers expert testimony in case of allegations
      during pediatric treatment. Methods Analysis of 374 written pediatric
      testimonies, documented between September 1st, 2000 and August 31st, 2014.
      Results 193 allegations against pediatricians were analysed separately for each
      sector of care (35% concerning outpatients, 28% normal inpatients, and 37%
      patients treated in an intensive care unit, ICU). Outpatient care led more
      frequently to malpractice claims regarding diagnosis, most often in the case of
      dysplasia of the hip (n=6), meningitis (n=5), and pneumonia (n=4). In inpatients,
      allegations regarding treatment errors were more common and frequently associated
      with extravasation injury (n=7), as well as periventricular leukomalacia (n=7),
      sepsis (=6), and intraventricular haemorrhage (n=4) in newborn infants on ICUs.
      Expert testimony confirmed allegations in 43% of the outpatients, 22% of the
      normal inpatients and 38% of the ICU patients. Discussion and conclusion The
      frequency of pediatric malpractice claims seems to depend primarily on the
      pattern of utilization of pediatric care services. Diagnosis-related
      constellations leading to malpractice claims in Germany are well-known
      internationally. Case analysis according to medical care sectors allows
      comprehensible conclusions for risk management.

PMID- 29050046
TI  - ?

PMID- 29050048
TI  - ?

PMID- 29050047
TI  - [Cooperation of the German Society of Orthopaedics and Trauma (DGOU) and the
      Orthopaedic Research Society (ORS)].

PMID- 29050049
TI  - ?

PMID- 29050050
TI  - ?

PMID- 29050051
TI  - ?

PMID- 29050052
TI  - ?

PMID- 29050053
TI  - ?

PMID- 29050054
TI  - Indication Criteria for Total Knee Arthroplasty in Patients with Osteoarthritis -
      A Multi-perspective Consensus Study.
AB  - Background and Objectives Knee osteoarthritis (OA) is a significant public health
      burden. Rates of total knee arthroplasty (TKA) in OA vary substantially between
      geographical regions, most likely due to the lack of standardised indication
      criteria. We set out to define indication criteria for the German healthcare
      system for TKA in patients with knee OA, on the basis of best evidence and
      transparent multi-stakeholder consensus. Methods We undertook a complex mixed
      methods study, including an iterative process of systematic appraisal of existing
      evidence, Delphi consensus methods and stakeholder conferences. We established a
      consensus panel representing key German national societies of healthcare
      providers (orthopaedic surgeons, rheumatologists, pain physicians, psychologists,
      physiotherapists), payers, and patient representatives. A priori defined
      consensus criteria were at least 70% agreement and less than 20% disagreement
      among the consensus panel. Agreement was sought for (1) core indication criteria
      defined as criteria that must be met to consider TKA in a normal patient with
      knee OA, (2) additional (not obligatory) indication criteria, (3) absolute
      contraindication criteria that generally prohibit TKA, and (4) risk factors that
      do not prohibit TKA, but usually do not lead to a recommendation for TKA. Results
      The following 5 core indication criteria were agreed within the panel: 1.
      intermittent (several times per week) or constant knee pain for at least 3 - 6
      months; 2. radiological confirmation of structural knee damage (osteoarthritis,
      osteonecrosis); 3. inadequate response to conservative treatment, including
      pharmacological and non-pharmacological treatment for at least 3 - 6 months; 4.
      adverse impact of knee disease on patient's quality of life for at least 3 - 6
      months; 5. patient-reported suffering/impairment due to knee disease. Additional
      indication criteria, contraindication criteria, and risk factors for adverse
      outcome were also agreed by a large majority within the multi-perspective
      stakeholder panel. Conclusion The defined indication criteria constitute a
      prerequisite for appropriate provision of TKA in patients with knee OA in
      Germany. In eligible patients, shared-decision making should eventually determine
      if TKA is performed or not. The next important steps are the implementation of
      the defined indication criteria, and the prospective investigation of predictors
      of success or failure of TKA in the context of routine care provision in Germany.

PMID- 29050056
TI  - Correction: Drink and Think: Impact of Alcohol on Cognitive Functions and
      Dementia - Evidence of Dose-Related Effects.

PMID- 29050055
TI  - [Polytrauma Management - Treatment of Severely Injured Patients in ER and OR].
AB  - The adequate treatment of severely injured patients is challenging and can only
      be successfully executed when it starts at the accident site and is continued in
      all treatment phases including the early rehabilitation phase. Treatment should
      be performed by an interdisciplinary team guided by a trauma surgeon in order to
      adequately manage the severe injuries some of which are life-threatening.
      Treatment of polytrauma patients is a key task of certified trauma centers and
      must follow standardized guidelines. For a successful therapy of severely injured
      patients lifetime training at regular intervals in well-established polytrauma
      concepts is a mandatory requirement.

PMID- 29050057
TI  - ?

PMID- 29050058
TI  - [Ambulant Anesthesia: Limits and Possibilities].
AB  - The number of operations carried out on an outpatient basis is increasing in
      Germany. This trend has been observed for years. The prerequisite is an
      infrastructure that is in line with guidelines. The competence of the anesthetist
      must not be restricted to that of a standard specialist anesthetist, but the
      physician should have experience in ambulatory anesthesia. Well-adjusted
      comorbidities of the patient are generally not a contraindication for an
      outpatient procedure. The heavily overweight patient can also be operated on an
      outpatient basis if he is compliant, comorbidities are well adjusted and
      intensive postoperative care is ensured. Obstructive sleep apnea syndrome is per
      se not a contraindication for carrying out a surgical intervention on an
      outpatient basis. The intensive postoperative care and the presence of a CPAP
      device are also important in the recovery room. An important decision criterion
      in cardiac patients is the determination of the metabolic equivalent (MET). A MET
      value > 4 is considered sufficient for outpatient procedures. Postoperatively,
      the patient can be discharged home when the surgeon and the anesthetist are
      convinced that the condition of the patient is stable. A sensible companion and
      instruction to the patient that he is not allowed to actively participate in road
      traffic are essential for discharge after surgery. The decision on outpatient or
      inpatient care must always be taken individually. It is not possible to make a
      general statement as to the manner in which an intervention should be carried.

PMID- 29050059
TI  - [Ambulant Anesthesia: Organization in Medical Practices and Hospitals].
AB  - Legislation, regulations and rules must be complied with when conducting ambulant
      surgeries and administering ambulant anesthesia. Additionally, there are social
      welfare legislation and regulations, as well as technical guidelines and
      standards that must be complied with, for instance, regarding the management of
      medical products or the disposal of waste and sewage in medical practices. At a
      country level, many of these regulatory areas are managed differently by each
      German state, and in some instances management differs significantly from one
      state to another. Social and employment legislation, as well as regulations for
      ambulant operating physicians and business operators have to be observed. In
      order to prevent nosocomial infections, there is a focus on maintaining
      compliance with hygiene regulations and the Infection Protection Act. There are a
      variety of possible operational models and ways to organize ambulant operating
      rooms. The particular model that is best for a specific practice will depend on
      the local circumstances. That being said, particular attention should be given to
      patient-centered, stress free surgical patient care, which should be prioritized
      over the business. Ambulant surgery can be performed in private practices, as
      well as hospitals, and the two usually differ significantly from one another. On
      the one hand there are the well-organized, high performing, private practices,
      which have a focus on ambulant surgeries, where the participating physicians
      contribute to the success of the practice. On the other hand, there are the often
      large and cumbersomely organized hospitals, where ambulant surgeries are viewed
      as more of a burden than as an additional source of income.

PMID- 29050060
TI  - [Ambulant Anesthesia: Regional Anesthesia for Ambulatory Patients].
AB  - Although regional anesthesia for ambulatory patients is feasible, effective and
      recommended, general anesthesia, analgosedation and monitored anesthesia care
      traditionally play a major role in the ambulatory setting. This discrepancy is at
      least partially caused by a more standardized and predictable process when using
      general anesthesia. High patient comfort, a low rate of complications and a rapid
      postoperative recovery are expected by all patients, irrespective of the type of
      anesthesia chosen and lie in the common interest of the anesthesiologist and the
      surgeon. A careful selection of suitable regional anesthesia procedures for
      equally suitable patients achieves these goals without loss of efficiency.

PMID- 29050061
TI  - [Perioperative Anaphylaxia on Drugs].
AB  - The diagnostic evaluation of perioperative anaphylaxia is of great importance for
      the medical care of the affected persons in the context of renewed interventions
      in general anesthesia. The most frequent triggers include muscle relaxants,
      antibiotics, latex and analgesics of the type of the cyclooxygenase inhibitors,
      but other perioperatively administered drugs such as opioids, anesthetics,
      benzodiazepines, dyes, disinfectants and even corticosteroids or drug additives
      may also be the cause in rare cases. The most important aim is therefore the
      identification of the responsible drug, for which a near-time allergological
      diagnosis should be carried out within the first 4 weeks to 6 months after the
      reaction. At the end of the examinations, the patient receives a structured
      allergy passport, which includes information on the drug reaction, the triggers
      and alternative medicines, as well as possible preventive measures for future
      surgical procedures. It should be noted, however, that the latter are not a
      guarantee that, upon renewed exposure to the causative medicinal product, there
      will be no, possibly even heavier, anaphylactic reaction.

PMID- 29050062
TI  - [Cerebral Emergency - Important Anesthesiological Aspects].
AB  - The anesthesiological management of cerebral emergency represents a great
      challenge for action under pressure and under time pressure and requires smooth
      interprofessional cooperation. The exact knowledge of the pathophysiological and
      pharmacological relationships is the basis for rapid identification of
      therapeutic influences and possible disturbing factors. In the acute situation,
      paCO2 and MAP are the central determinants for the anesthetist to ensure cerebral
      perfusion and the resulting cerebral oxygenation. Especially in patients with
      SHT, a difficult airway must always be expected. Knowledge of the appropriate
      steps and the necessary equipment must be available. In patients under
      anticoagulant therapy, written instructions for suspending this therapy are
      extremely helpful. Interventional thrombectomy is a new emergency situation for
      the anesthetist. The door-to-needle time has to be kept as short as possible by
      defined treatment paths and rapid goal-oriented work. Every emergency also
      creates a stressful reaction in those treating the patient - in a sense, the
      cerebral emergency "in us". This has a decisive influence on the perception and
      action of the individual and the entire team.

PMID- 29050063
TI  - [Update in Obstetric Anesthesia: Tried and Trusted Methods, Controversies and New
      Perspectives - Part 1].
AB  - Since 1975, a plethora of lectures within the context of annual meetings relevant
      for the clinical care has been summarized in "what's new in obstetric anesthesia"
      by the Society for Obstetric Anesthesia and Perinatology which can be recommended
      to everyone interested in anaesthesiology in the delivery room. After the death
      of Gerard W. Ostheimer, Professor of Anaesthesiology at Brigham and Women's
      Hospital in Boston, Massachusetts, it became renamed the Gerard W. Ostheimer
      "what's new in obstetric anesthesia" lecture to honor his contributions to
      regional anesthesia and obstetric anaesthesia. Each year the event held by
      selected professional representatives and their imprint in leading anesthesia
      journals give insight into a critical appraisal of recent literature and the
      possible consequences for - but not only - the anaesthetic delivery room
      practice.A similar event has been established in Germany for more than 16 years:
      the obstetrical anesthesia symposium of the academic working group "regional
      anesthesia and obstetrical anesthesia" 1, 2."Evergreens" or "hot topics" with
      regard to anaesthesiological delivery room practice are presented and discussed
      regularly. The lectures often reveal the subtle change of the issues being
      debated much earlier than traditional textbook chapters do. This manuscript
      summarizes important findings from the last symposium held in 2016. Part I
      focuses on relevant causes for maternal morbidity and mortality as well as
      preventive measures, pregnancy in obese patients and sepsis in obstetric
      anaesthesia. Part II addresses established standards and new perspectives in the
      direct obstetric setting regarding epidural analgesia, post-dural puncture
      headache, anaesthesia and analgesia during and after caesarean section,
      haemodynamic monitoring during cesarean section and postpartum haemorrhage.

PMID- 29050065
TI  - [Status of PD-L1 testing in non-small cell lung cancer in China].

PMID- 29050064
TI  - Bilateral anatomic resection of the ventral parts of the paramedian sectors of
      the liver with total caudate lobectomy for deeply/centrally located liver tumors:
      a new technique maximizing both oncological and surgical safety.
AB  - Systematic resection of the tumor-bearing portal territory is reportedly
      correlated with an improved survival of patients with liver tumors, especially in
      hepatocellular carcinoma. Despite advances in surgical management, however,
      anatomic resection of deeply/centrally located tumors remains a challenging
      procedure not only with technical difficulty but also because of decreased
      hepatic functional reserve frequently observed due to underlying liver disease.
      In this report, we have reported a novel technique that allows a promising
      approach for deeply/centrally located tumors with maximizing both the surgical
      and oncological safety. Bilateral anatomic resection of the ventral parts of the
      paramedian sectors (BVPM) offers a sufficient surgical window for safe access to
      the perihilar region. This technique is based on Hjortsjo's theory for liver
      anatomy and enables systematic removal of the 3rd-order portal territories. In
      addition, the current technique is advantageous in minimizing the loss of the
      normal liver parenchyma without leaving ischemia or congestion in the future
      liver remnant. Of the seven consecutive patients who were treated with this
      procedure, all the patients achieved R0 resection with acceptable rate of major
      morbidity (1/7, 14%). The BVPM may offer a safe and maximized chance of curative
      resection for deeply/centrally located liver tumors.

PMID- 29050066
TI  - [Roles of pathologists in era of precision therapy of cancer: comments on the
      Food and Drug Administration of the United States approval of pembrolizumab for
      microsatellite instability-high cancer therapy].

PMID- 29050067
TI  - [Neuropathologic findings in intractable epilepsy: a clinicopathologic analysis
      of 822 cases].
AB  - Objective: To investigate the clinicopathologic characteristics of intractable
      epilepsy. Methods: Based on the classification criteria proposed by the
      International League Against Epilepsy (ILAE), a retrospective analysis of the
      pathological characteristics was done in 822 patients who underwent epilepsy
      surgery in Sanbo Brain Hospital, Capital Medical University, from June 2008 to
      December 2012. Results: The mean age of epilepsy onset was 9.9 years, mean
      duration of epilepsy was 11.9 years. Complex partial seizures were the main
      presenting features. Histopathological study showed 33 cases (4.01%) with mild
      forms of cortical malformations, 690 cases (83.94%) with focal cortical dysplasia
      (FCD) and 99 cases with others (including 39 pure hippocampal sclerosis, 20
      cystosclerosis, 19 Sturge-Weber syndrome, 8 tuberous sclerosis complex, 6 without
      significant pathological changes, 5 gyral malformations and 2 hamartoma). Among
      the 690 FCD cases, 106 were FCD typeI, 91 were FCD typeII and 493 were
      FCDIII(IIIa: 160, IIIb: 106, IIIc: 26 and IIId: 201). Conclusions: FCDIIId is the
      most common histopathological subtype causing intractable epilepsy, mainly due to
      focal hypoxia/ischemia in the perinatal period, which results in scarring of
      local brain tissue; this is followed by other isolated forms of FCD (FCDIand
      FCDII), and then FCD IIIa and FCD IIIb. The reason to distinguish isolated forms
      of FCD (types I and II) from FCD III and to subclassify FCD III is to allow
      better definition of cortical dyslamination. Therefore, the pathogenic factors of
      intractable epilepsy can be grouped in greater details, and facilitate the
      diagnosis and potential curative treatment of intractable epilepsy.

PMID- 29050068
TI  - [Diagnostic and prognostic roles of loss of CIC protein expression in
      oligodendroglial tumors].
AB  - Objective: To investigate the usefulness of loss of CIC expression as the
      prescreening detection of 1p/19q co-deletion in the diagnosis of oligodendroglial
      tumors and its prognostic implication. Methods: The retrospective study included
      113 oligodendroglial tumors diagnosed in the Department of Pathology, Xuanwu
      Hospital, Capital Medical University. Expression of CIC protein was detected by
      immunohistochemistry, and the 1p/19q co-deletion by fluorescence in situ
      hybridization in all the tumors; and the correlation of the loss of protein and
      1p/19q co-deletion with prognosis was assessed. Results: The rate of negative CIC
      protein expression was 59.3% (67/113) in 113 oligodendroglial tumors. CIC protein
      expression was differentially lost in various gliomas, 85.7% (42/49) in pure
      oligodendrogliomas and 39.1% (25/64) in mixed oligodendroglial tumors (P<0.01).
      The loss of CIC protein expression showed a sensitivity of 76.1% (54/71),
      specificity 71.1% (27/38), false positive rate of 16.9% (11/65), and a false
      negative rate of 38.6% (17/44). In 63 cases integrated diagnosis as
      oligodendroglial tumors with mutant IDH and 1p/19q co-deletion, the loss of CIC
      protein expression was 81.0% (51/63); the sensitivity and specificity were
      increased to 81.0% (51/63) and 76.9% (20/26), and the false positive rate and
      false negative rate decreased to 10.5% (6/57) and 37.5% (12/32), respectively. By
      using Kaplan-Meier analysis, the CIC negative group showed a trend towards better
      outcome than the CIC positive group, but there was no statistical difference
      (overall survival: P=0.218; progression free survival: P=0.249). Conclusions:
      Detection of the lost CIC protein expression can predict the chromosome 1p/19q co
      deletion. In oligodendroglial tumors with IDH mutant and 1p/19q co-deletion,
      there is no relation between prognosis and CIC protein expression.

PMID- 29050069
TI  - [miR-449a is a potential epigenetic biomarker for WNT subtype of
      medulloblastoma].
AB  - Objective: To identify the candidate epigenetic biomarkers of Wnt subtype of
      medulloblastoma(MB). Methods: MicroRNAs(miRNAs) expression array was used to
      detect the expression of miRNAs in MB cell lines with or without treatment by
      demethylation reagent. Nanostring gene expression array was used to detect the
      expression level of mRNA in 45 samples of primary MB. Molecular subtyping was
      performed based on the NanoString data. The status of methylation was confirmed
      by methylation specific PCR. The expression of candidate miRNA was confirmed by
      real-time PCR. Results: All 45 MBs except one were classified into the four
      molecular groups: 4 in WNT group, 8 in SHH group, 16 were in Group3 and 16 in
      Group4. Methylation specific PCR (MSP) assay confirmed miR-449a was silenced due
      to aberrant DNA methylation in MB cell lines.WNT subtype of MBs showed relatively
      higher expression of miR-449a comparing with other subgroups. Conclusion: MiR
      449a, a candidate tumor suppressor gene regulated by hypermethylation, is a novel
      potential epigenetic marker for WNT subtype of MBs.

PMID- 29050070
TI  - [Application of ATRX in diagnosis and prognostic evaluation of glioma].
AB  - Objective: To investigate the diagnostic and prognostic implications of ATRX
      mutation and p53 mutation in patients with glioma. Methods: The clinicopathologic
      and molecular features of Chinese adult glioma patients, including diffuse and
      anaplastic astroastrocytoma with IDH mutation, oligodendroglioma and anaplastic
      oligodendroglioma with IDH mutation and 1p/19q co-deletion and diffuse
      astroastrocytoma with IDH wild type were reviewed and tested for ATRX loss
      expression and p53 overexpression. Results: Loss of ATRX expression was seen in
      85.19% (23/27) diffuse and anaplastic astroastrocytoma with IDH mutation, higher
      than that of oligodendroglial tumors (0/53; P<0.01). Loss of ATRX expression was
      strongly linked to p53 overexpression(69.57%, 16/23). The patients who lost ATRX
      expression combined with normal p53 expression survived longer(P=0.013).
      Conclusions: ATRX mutation is a molecular marker for astrocytic tumors. ATRX
      mutation combined with p53 mutation can predict prognosis of patients with
      glioma.

PMID- 29050071
TI  - [Poorly-differentiated chordoma with INI1 loss: a clinicopathologic study].
AB  - Objective: To analyze the clinicopathologic characteristics of poorly
      differentiated chordoma with INI1 loss in children and to discuss the
      differential diagnosis. Methods: The clinical, radiological, histopathological
      profiles and molecular pathologic characteristics of two pediatric poorly
      differentiated chordoma cases with INI1 loss were reviewed. Results: The patients
      were a girl and a boy. Both lesions involved the slope. Both patients were
      presented with progressive muscle weakness or neck pain. Radiological examination
      showed clivus bone destruction and compression of the brain stem and cervical
      spinal cord. Histologically, the tumor cells lacked typical organization and were
      associated with inflammatory cells infiltration. On high power field, the tumor
      cells were ovoid or fusiform with prominent atypia, vacuolated nuclei and
      prominent nucleoli. By immunohistochemistry, the tumor cells expressed
      cytokeratin, epithelial membrane antigen, brachyury and were negative for INI1.
      In both cases, INI1 gene deletion was detected by FISH. Conclusions: Poorly
      differentiated chordoma with INI1 loss mainly occurs in children. The morphology
      is different from classical chordoma.INI1 gene deletion is detectable by FISH. It
      can be distinguished from atypical teratoid/rhabdoid tumors and other neoplasms
      by the identification of nuclear brachyury expression. The loss of INI1
      expression in poorly-differentiated chordoma might be associated with a poorly
      differentiated morphology and an adverse prognosis.

PMID- 29050072
TI  - [Loss of BRCA associated protein 1 expression in malignant mesothelioma and its
      diagnostic application].
AB  - Objective: To investigate the expression of BRCA-associated protein 1 (BAP1) in
      malignant mesothelioma, non-small cell lung cancer and carcinosarcoma, and its
      application in the differential diagnosis. Methods: Twenty-two cases of malignant
      mesothelioma including 17 epithelioid type, 2 sarcomatoid type and 3 biphasic
      type were collected.As the study control, 80 non-small cell lung cancers
      infringement pleural membrane(including 40 lung adenocarcinomas and 40 lung
      squamous cell carcinomas) and 15 carcinosarcomas were included. BAP1 expression
      was detected using immunohistochemical method. A differential diagnosis antibody
      panel, including calretinin, WT1, CK5/6, D2-40, CAM5.2, CEA, TTF1, Napsin A, p63
      and p40 was tested in all cases. Results: All 80 cases of non-small cell lung
      cancer and 15 cases of carcinosarcoma were BAP1 positive. In contrast, 64%
      (14/22) of malignant mesotheliomas lost BAP1 expression (P<0.01). Addition of
      BAP1 to the mesothelioma marker panel, the diagnostic accuracy of malignant
      mesothelioma was enhanced to 93%. Focal expression of BAP1 in tumors suggested
      multiclonal evolution of mesothelioma. Conclusions: Loss of BAP1 expression helps
      to confirm the diagnosis of malignant mesothelioma whereas all non-small cell
      lung cancer expresses BAP1. It is therefore recommended that BAP1 can be used in
      conjunction with other immunohistochemical markers to improve the diagnostic
      accuracy of malignant mesothelioma.

PMID- 29050073
TI  - [Clinicopathologic features of three cases of erythropoietic protoporphyria with
      liver involvement].
AB  - Objective: To investigate the clinicopathologic features of the erythropoietic
      protoporphyria (EPP) with liver involvement. Methods: The clinical findings and
      hepatic biopsy of 3 cases of EPP diagnosed between July, 2011 to August, 2014
      with liver involvement were reviewed, with relevant literature review. Results:
      All patients presented with persistent and refractory abdominal pain, with
      obvious jaundice and deranged liver function. Imaging showed homogeneous
      hepatomegaly in all patients. Histologically, the hepatocytes were edematous, and
      contained numerous cytoplasmic globular brown pigments and bile pigments, which
      were also found in Kupffer cells, in the bile canaliculi and in some of dilated
      sinusoid. The pigments were of different sizes and showed uneven distribution.
      Some pigments showed bright red or yellow birefringence with a distinctive
      central maltese cross configuration on polarizing microscopy. Furthermore, some
      hepatocytes showed piecemeal necrosis and steatosis, the portal tracts were
      usually infiltrated by lymphocytes, with fibroplasia and biliary ductular
      reaction. There was no dilatation of intrahepatic bile ducts. Conclusion: Full
      understanding of the clinical and pathological features of EPP with liver
      involvement can help to recognize this small group of patients, and to offer
      proper effective treatments.

PMID- 29050074
TI  - [Clinicopathologic characteristics and prognosis of neoplastic cell-rich mixed
      cellularity classic Hodgkin lymphoma].
AB  - Objective: To investigate the clinicopathologic characteristics of neoplastic
      cell-rich mixed cellularity classical Hodgkin lymphoma(MCCHL-R) and to compare
      the prognosis with typical mixed cellularity classic Hodgkin lymphoma(MCCHL).
      Methods: Fifty-four patients with MCCHL-R(the tumor cells >10%) and 65 patients
      with typical MCCHL identified from 1 721 Hodgkin lymphomas were reviewed to
      compare the clinicopathological characteristics including morphologic and
      immunophenotypic features, EBV infection status, clinical therapy and overall
      survival. Results: The median age of the patients of MCCHL-R was 28.5
      years(range: 9-76 years, male?female=1.6?1.0). Twenty-seven patients(50.0%) had B
      symptoms. Most patients had cervical lymph node involvement(81.5%, 44/54).
      Mediastinum and spleen involvement were seen in 69.2%(36/54) and 24.1%(13/54),
      respectively. Extranodal non-lymphoid organ involvement was seen in 41.3%(19/46)
      cases. Morphologically, lymph node architectures were effaced at various degree
      with large neoplastic cells of variable morphology, including Hodgkin/Reed
      Sternberg(H/RS) cells and anaplastic large cells. There were abundant background
      heterogeneous admixtures of non-neoplastic inflammatory and accessory cells that
      were predominant mature small lymphocytes. All tumors were positive for CD30 and
      weakly positive for PAX5. Epstein-Barr encoded RNA(EBER)detectable by in situ
      hybridization was seen in 39.0% cases. Forty-six patients had a median follow-up
      time of 32.5 months(range: 5-128 months) and the 5-year survival rate for stage I
      II and stage III-IV patients were 91.7% and 50.1%, respectively(P<0.05). The 5
      year survival rate for MCCHL-R was lower than typical MCCHL patients. Single
      factor analysis showed that age of >45 years, extranodal involvement and stage
      III-IV were correlated with poorer 5-year survival rate(P<0.05). Multiple factors
      Cox proportional hazards regression showed that extranodal involvement was the
      independent prognostic factor(RR: 4.352, 95%CI: 1.122-16.879, P<0.05).
      Conclusions: MCCHL-R is more common in young people. The tumor has pathological
      features of classic Hodgkin lymphoma enriched with the tumor cells(>10%) and
      similar immunophenotype to classical Hodgkin lymphoma. Compared with typical
      MCCHL, extranodal disease is an independent prognostic factor of MCCHL-R.

PMID- 29050075
TI  - [Specific cytotoxicity of a novel HER2-based chimeric antigen receptor modified T
      lymphocytes against HER2-positive tumor cells].
AB  - Objective: To construct the third generation chimeric antigen receptor based on a
      novel humanized anti-HER2 H1-2 scFv, and to investigate the specific cytotoxicity
      of H1-2 CAR modified T lymphocytes(CAR-T) against HER2(+) tumor cells. Method:
      The expression cassette of the third generation CAR gene and anti-HER2 H1-2 scFv
      were constructed and cloned into lentivirus transfer plasmid, and then the third
      generation H1-2 CAR was transduced into human T lymphocytes using
      lentivirus.Enzyme linked immunosorbent assay was used to detect the expression of
      cytokines IL2, and LDH release assay was used to detect the cytotoxic effect of
      the H1-2 CAR-T.Finally, NOD/SCID mice and HER2(+) breast cancer cell line SKBR3
      were used to detect the anti-tumor effect of H1-2 CAR-T in vivo. Results: The
      third generation H1-2 CAR was successfully constructed.H1-2 CAR-T secreted high
      dose of IL2 after confrontation with HER2(+) breast cancer cells.In vitro, the
      cytolytic rate of H1-2 CAR-T on high expression HER2(+) tumor cells was
      significantly higher than that in low expression HER2 or non-expression HER2
      tumor cells. At the efficacy to target ratio of 20, the cytolytic rate of H1-2
      CAR-T against breast cancer cell SK-BR-3 could reach (90.1+/-2.8)%, while the
      cytolytic rate of H1-2 CAR-T against HER2(-) breast cancer cell MDA-MB-231 was
      only (13.5+/-4.7)%. In the mouse xenograft tumor model, H1-2 CAR-T cells
      inhibited breast cancer growth in vivo.At the end of the experiments, the average
      tumor weight in the H1-2 CAR-T cell treatment group was (0.7+/-0.1) g, the non
      transfected T cell therapeutic group was (1.2+/-0.2) g, and the PBS group was
      (1.2+/-0.2) g. There was significant difference between the H1-2 CAR-T
      therapeutic group and the non-transfected T cell therapeutic group (P<0.05).
      However, there was no significant difference between the non-transfected T cell
      therapeutic group and the PBS treatment group (P>0.05). Conclusion: The HER2
      sepcific H1-2 CAR-T cells specifically kill HER2 positive cells, and further
      studies on CAR-T cells for the treatment of HER2(+) cancers are useful.

PMID- 29050076
TI  - [Secretory carcinoma of breast: a clinicopathologic analysis of 3 cases].

PMID- 29050077
TI  - [Detection of fusion gene transcript in formalin-fixed paraffin-embedded
      myxoid/round cell liposarcoma tissues by improved reverse transcription
      polymerase chain reaction].

PMID- 29050079
TI  - [Pineal malignant solitary fibrous tumor: report of two cases].

PMID- 29050078
TI  - [Left cervical lymph node enlargement with pain].

PMID- 29050080
TI  - [Granuloma faciale: report of a case].

PMID- 29050081
TI  - [Infantile Dieulafoy's disease of bronchus: repor/t of a case//].

PMID- 29050082
TI  - [Malignant giant cell tumor of tendon sheath in finger: report of a case].

PMID- 29050083
TI  - [Primary ameloblastic carcinoma of maxilla with extensive squamous
      differentiation areas of dedifferentiation: report of a case].

PMID- 29050084
TI  - [Recent progress in application of exosome in diagnosis and treatment of
      gliomas].

PMID- 29050085
TI  - [Research progress and application of ROS1 fusion detection in non-small cell
      lung cancer].

PMID- 29050086
TI  - [Exploration of transoral minimal invasive surgery suitable to China's domestic
      features].

PMID- 29050087
TI  - [Study on the correlation between meteorological factors and acute otitis media
      in outpatients of children in Beijing].
AB  - Objective: To explore the characteristics of acute otitis media(AOM) in children
      in Beijing and its correlation with meteorological factors. Methods: Data were
      collected in 2011-2013 in the Otolaryngology Department of Capital Institute of
      Pediatrics. AOM in children with relevant information, such as age, sex and
      season, with the same period of the Beijing municipal meteorological data (the
      average temperature, average pressure, average wind speed, humidity and PM2.5)
      were compared to analysis the relationship of meteorological environmental
      parameters and the onset of AOM in children. Results: Annual morbidity of AOM was
      7 589, 8 245, 7 242 respectively, no obvious difference(P=0.761). It was noted
      that one peak could be seen in December, and a valley in February, followed by
      August. Summer was less than the other three seasons (P<0.05). The morbidity of
      AOM had a small peak within one year after birth, then reached peak at the age of
      about 4, and then reduced gradually. In different age groups, male patients were
      higher than those of female. The incidence of AOM was positively correlation
      tendency with air pressure and PM2.5 (r=0.333, 0.093, P=0.000, 0.002), which was
      negatively correlation tendency with daily temperature or humidity (r=-0.327, 
      0.195, P=0.000, 0.000). Conclusions: The incidence of AOM of children in Beijing
      changes with age, and has obvious seasonal variation. There may be some
      correlation between the meteorological factors and the incidence of AOM in
      children.

PMID- 29050088
TI  - [Laryngeal endoscopic cricopharyngeal myotomy for cricopharyngeal achalasia post
      stroke].
AB  - Objective: To explore the safety and validity of endoscopic cricopharyngeal
      myotomy in patients with cricopharyngeal achalasia. Methods: A total of 19
      patients with cricopharyngeal achalasia suffered from sustained dysphagia were
      enrolled in this study. The patients were divided into transcervical
      cricopharyngeal myotomy(CPM) group and endoscopic CPM (ECPM) group. Swallowing
      function and complications were evaluated.SPSS7.0 software was used to analyze
      the data. Results: The swallowing function improved significantly in seven
      patients in ECPM group, and 9 patients improved in CPM group.The video
      fluoroscopic swallowing study(VFSS)-swallowing score, VFSS-aspiration score and
      drinking test score were (3.1+/-1.1), (3.4+/-0.8) and (2.0+/-0.6)in post-ECPM,
      (3.4+/-1.4), (3.0+/-0.9) and (2.2+/-0.6)in post-CPM. No statistical difference
      was found in validity between CPM group and ECPM group(t=-0.435, t=1.086, t=
      0.607, P>0.05). No statistical difference was observed on the occurrence of
      complication between two groups. Only one patient had subcutaneous emphysema
      after operation in ECPM. Conclusions: New surgical instruments and endoscopic
      surgical technique were safe and effective for cricopharyngeal achalasia. Because
      these instruments are cheaper, laryngeal endoscopic cricopharyngeal myotomy is
      easier to be popularized more easily than microscopic laser assistted CPM.

PMID- 29050089
TI  - [A retrospective analysis of CO(2) laser and microdebrider for the treatment of
      severe juvenile on-set recurrent respiratory papillomatosis].
AB  - Objective: Juvenile on-set recurrent respiratory papillomatosis (JORRP) can be an
      aggressive and potentially life-threatening disease. To emphasize the importance
      of complication prevention in local excision surgery, the single-center
      experience of RRP treatment in a group of patients with relatively short
      recurrence-free-interval (>4 times/yrs) was reported. Methods: Data of 49
      patients underwent papilloma resection during 2002-2013 were retrospectively
      analyzed. Combined techniques of laser microsurgery and microdebriders were used
      to remove papillomas, prevent the formation of scar tissue and improve
      respiratory distress. Forty-nine cases were followed up for 99.0[74.5;
      121.0]months, ranging from 39 to 185 months. The age of disease onset was 2[1; 3]
      years old. Most of the patients had difficulty in breathing(42 of 49 cases).
      Seven patients had hoarseness.53.0% patients had subglottic or trachea
      papillomatosis spreading. The rate of complications, synechia formation, tracheal
      stenosis, needing for tracheostomy, mortality was recorded. Patients were
      followed up for at least three years. The characteristics of the patients,
      improvement in symptoms, recurrence-free interval, and the rate of tracheal
      extubation were evaluated. Wilcoxon signed ranks test and chi-square test were
      used for data comparation. Results: Long-term relieve in disease(<=2 surgeries
      were needed/year) were achieved in 29(59.1%) subjects, in which 8(16.3%) of the
      subjects did not need surgical treatment for at least 3 years. Long-term relieve
      had been achieved in 25 of subjects who did not accept tracheostomy. Seven
      subjects did not need surgical treatment for at least 3 years. The rate of
      successful tracheal extubation was 53.8% in 13 patients who had undergone
      tracheostomy. Three cases dead of intrapulmonary spread. Conclusions: Combined
      techniques of laser microsurgery and microdebriders are effective in improvement
      in both respiratory distress and voice quality. The combined technique are
      helpful to avoid inevitable long-term stenotic complications, ultimately
      affecting the quality of life.

PMID- 29050090
TI  - [Laryngotracheal resection and reconstruction for the treatment of acquired
      laryngotracheal stenosis].
AB  - Objective: To analyze the efficacy of laryngotracheal resection and
      reconstruction for acquired laryngotracheal stenosis, and to discuss the
      prevention of complication. Methods: The clinical outcomes of seventy patients
      with acquired laryngotracheal stenosis, treated with laryngotracheal resection
      and reconstruction were retrospectively reviewed between January 2007 and
      December 2016. The degree of stenosis was classified according to Myer-Cotton
      classification as follows: grade II(n=7), grade III(n=38) and grade IV(n=27). The
      stenostic extension ranged from 0.5-4.0 cm (median 2.0 cm), the resection
      extension ranged from 1.0-5.0 cm (median 3.0 cm). Fifty-three stenosis originated
      from iatrogenic (endotracheal tubes and/or tracheostomy), 17 originated from
      cervical trauma. Results: Thirty patients were treated by the resection of
      tracheal and primary anastomosis. Twenty-nine patients were treated by resection
      and reconstruction and supported by T-tube. Eleven patients with subglottic
      stenosis were treated by complete resection of tracheal lesion and the arch of
      cricoid cartilage, together with trachea and thyroid cartilage anastomosis with
      tracheotomy. Six months after surgery, the outcome was good to satisfactory in 65
      patients (92.9%). Five patients failed(3 were tracheotomized and 2 were supported
      by T-tube). Complications included granulation tissue formation(n=15),
      anastomoticseparation(n=9), restenosis of anastomosis(n=9), wound infection(n=5)
      and subcutaneous emphysema(n=7). In 15 patients with granulation tissue, 10
      patients needed endoscopic resection, and 5 patients resulted in anastomotic
      stenosis. No injury to recurrent laryngeal nerve was found. Three patients with
      trachoesophageal fistula were repaired. Conclusion: Laryngotracheal resection and
      reconstruction is an effective surgical method for acquired laryngotracheal
      stenosis, which has a higher successful rate and shorter therapeutic period.

PMID- 29050091
TI  - [Value of modified Killian's method in diagnosis of congenital pyriform sinus
      fistula].
AB  - Objective: To investigate the feasibility and significance of modified
      Killian(MK) method in the clinical diagnosis of congenital pyriform sinus
      fistula(CPSF) by electronic laryngoscopy. Methods: The following examinations
      were performed for 30 suspected cases of CPSF, including the traditional
      electronic laryngoscopy, MK examination(modified Killian position+ head rotation+
      the Valsalva maneuver), barium swallow X-ray(BSX) and CT , and a prospective
      comparison among them were done. Patients were divided into two groups according
      to their age: young age group(<=14 years old) and older age group (>14 years
      old). The results of MK examination from the patients were analyzed and the
      positive diagnostic rates (PDR) between groups were compared by using chi(2)
      tests. Results: Sinuses in 20 of 30 patients were depicted from pyriform sinus in
      BSX, and the PDR was 66.7%(20/30). The PRD of CT was 83.3%(25/30). The presence
      of air bubbles around the upper lobe of the thyroid gland or at the inferomedial
      edge of cricothyroid joints, morphological changes of thyroid grand as well as
      pseudo-fistula formation on lower neck were detected clearly on CT. Comparing to
      the traditional electronic laryngoscopy, the effect of exposing piriform fossa
      fistula by MK examination is significant(chi(2)=17.05, P<0.05), with the PDR of
      13.3%(4/30) and 76.7%(23/30) respectively. Nevertheless, comparing to BSX and CT,
      there were no statistically significant differences in the effect to diagnose
      CPSF (chi(2)=0.31, chi(2)=0.10 respectively, P>0.05). The PDR of MK in older
      group is significantly higher than younger group(chi(2)=6.68, P<0.05).
      Conclusions: MK examination can clearly reveal the hypopharyngeal anatomical
      structure and detect the sinus of CPSF .It could be a safe, feasible, convenient
      and economical method as an application in preoperative diagnosis and follow-up
      examination of clinical suspected CPSF.

PMID- 29050092
TI  - [Risk factors and survival analysis for synchronous esophageal carcinoma in
      patients with hypopharyngeal carcinoma].
AB  - Objective: To investigate the risk factors and survival status of hypopharyngeal
      carcinoma with synchronous second primary carcinoma of the esophagus. Methods:
      One hundred and sixty patients with newly diagnosed hypopharyngeal carcinoma from
      January 2009 to December 2012 were retrospectively reviewed. The clinical data,
      tumor-related information and follow-up results were collected and analyzed.
      Results: Forty-three synchronous esophageal carcinomas (27%) were detected in 160
      patients with hypopharyngeal carcinoma, and most patients (72%) were at an early
      stage. On univariate analysis, the median age of less than 55 years old
      (chi(2)=4.525, P=0.033), excessive alcohol consumption (chi(2)=6.942, P=0.008)
      and invasion site more than 3 anatomical regions (chi(2)=21.503, P=0.000) had a
      significant correlation with the occurrence of synchronous esophageal carcinomas.
      Multivariate analysis showed that excessive alcohol consumption (OR=4.787,
      P=0.029) and invasion site more than 3 anatomical regions (OR=14.391, P=0.000)
      were independent risk factors. The median survival time was 26 months in 43
      patients with synchronous esophageal carcinomas, which was significantly lower
      than that (58 months) in patients without secondary primary esophageal carcinomas
      (chi(2)=11.981, P=0.001). Conclusions: There is a high incidence of synchronous
      esophageal carcinoma in hypopharyngeal carcinoma patients, affecting the
      prognosis of hypopharyngeal carcinoma. Surveillance for esophageal carcinomas in
      patients with hypopharyngeal carcinoma, especially in excessive alcohol drinkers,
      is warranted.

PMID- 29050093
TI  - [Clinical significance of lymphatic metastasis between sternocleidomastoid and
      sternohyoid muscle in papillary thyroid cancer].
AB  - Objective: To explore the clinical significance of metastasis of lymph nodes
      between sternocleidomastoid and sternohyoid muscle (LNSS) in papillary thyroid
      cancer (PTC). Methods: A total of 175 patients with PTC who underwent
      thyroidectomy with LNSS dissection were retrospectively analyzed. Univariate and
      multivariate Logistic regression analyses were used to determine the independent
      risk factors for LNSS metastasis in PTC. Results: The rate of detectable LNSS was
      70.9% (124/175) and metastasis rate was 7.4% (13/175). Of 13 cases with LNSS
      metastasis, 10 with the coexistence of cervical lymph node metastasis. Univariate
      Logistic regression analysis showed that multiple focal cancer, tumor located in
      the lower pole of thyroid, belt-shaped muscle invasion, lateral cervical lymph
      node metastasis, cN+ , the number of cervical lymph nodes with metastasis and the
      number of lymph nodes with metastasis in level IVwere the risk factors for LNSS
      metastasis (P<0.05). Multivariate Logistic regression analysis suggested that
      tumor located in the lower pole of thyroid and the number of cervical lymph nodes
      with metastasis >6 were the independent risk factors for LNSS metastasis
      (P<0.05). Given the number of cervical lymph nodes with metastasis as a predictor
      for the LNSS metastasis, the sensitivity was 92.3%, the specificity was 66.7% and
      the accuracy rate was 68.6%. Conclusions: LNSS metastasis is commom in PTC, with
      a metastasis rate of 7.4%. PTC in the lower pole of thyroid and the number of
      cervical lymph nodes with metastasis > 6 are independent risks for LNSS
      metastasis.

PMID- 29050094
TI  - [Relationship between Work II type of congenital first branchial cleft anomaly
      and facial nerve and surgical strategies].
AB  - Objective: To investigate the relationship between Work II type of congenital
      first branchial cleft anomaly (CFBCA) and facial nerve and discuss surgical
      strategies. Methods: Retrospective analysis of 37 patients with CFBCA who were
      treated from May 2005 to September 2016. Among 37 cases with CFBCA, 12 males and
      25 females; 24 in the left and 13 in the right; the age at diagnosis was from 1
      to 76 ( years, with a median age of 20, 24 cases with age of 18 years or less and
      13 with age more than 18 years; duration of disease ranged from 1 to 10 years
      (median of 6 years); 4 cases were recurren after fistula resection. According to
      the classification of Olsen, all 37 cases were non-cyst (sinus or fistula).
      External fistula located over the mandibular angle in 28 (75.7%) cases and below
      the angle in 9 (24.3%) cases. Results: Surgeries were performed successfully in
      all the 37 cases. It was found that lesions located at anterior of the facial
      nerve in 13 (35.1%) cases, coursed between the branches in 3 cases (8.1%), and
      lied in the deep of the facial nerve in 21 (56.8%) cases. CFBCA in female with
      external fistula below mandibular angle and membranous band was more likely to
      lie deep of the facial nerve than in male with external fistula over the
      mandibular angle but without myringeal web. Conclusions: CFBCA in female patients
      with a external fistula located below the mandibular angle, non-cyst of Olsen or
      a myringeal web is more likely to lie deep of the facial nerve. Surgeons should
      particularly take care of the protection of facial nerve in these patients, if
      necessary, facial nerve monitoring technology can be used during surgery to
      complete resection of lesions.

PMID- 29050095
TI  - [Revisional radical mastoidectomy surgeries--25 cases'experience].
AB  - Objective: To analyze the risk factors of failure to dry ear after radical
      mastoidectomy and discuss key points in revisonal surgery. Methods: Clinical data
      of 25 patients(32 ears) with revisonal mastoidectomy were analyzed. The
      preoperative temporal bone CT findings, intra-operative findings, surgical
      procedures, postoperative operating cavities and aural abilities were recorded
      and analyzed. Results: All patients received preoperative temporal bone CT
      followed by revisonal radical mastoidectomy under microscope and general
      anesthesia. Among the revisonal surgeries, 19 ears(59.4%) presented cholesteatoma
      and 13 ears(40.6%) had no cholesteatoma. In addition, the inadequate opening for
      mastoid cavity and incompleted removal of the pathological tissues accounted for
      90.6%(29/32), the insufficient drainage of surgical cavity for 90.6%(29/32), the
      lesions in tympanic ostium of eustachian tube for 31.2%(10/32), the improper
      operation procedures and selection of incision for 15.6%(5/32). As for the re
      operation of the modified canal wall down mastoidectomy, tympanoplasty(II) plus
      plastic repairing of cavity of concha were performed in 14 ears(43.8%), the
      modified canal wall down mastoidectomy, tympanoplasty(II) plus reconstruction
      posterior bony wall of ear canal in 2 ears(6.2%); the modified canal wall down
      mastoidectomy, tympanoplasty(III) plus plastic repairing of cavity of concha in
      10 eras(31.3%), the modified canal wall down mastoidectomy, tympanoplasty(III)
      plus reconstruction posterior boney wall of ear canal in 1 ear(3.1%); the radical
      mastoidectomy plus plastic repairing of cavity of concha in 5 ears(15.6%).
      Lodoform gauzes were packed in surgical cavity for 2 weeks and the antibiotic was
      used for 3 days after surgery. All patients had dressing of ears and their ears
      were dropped with ofloxacin regularly. The dry ear time ranged from 4 to 8 weeks,
      the average point was the 5th week. During a period of 6-18 months for follow-up,
      all patients got dried ears. The epithelialization of the operating cavity was
      well and the tympanic membranes were integrity. There was not pus in surgical
      cavities. Neither granulation tissue nor cholesteatoma was found to reoccur. Both
      pure tone air hearing thresholds and air-bone gap decreased in 27 ears after the
      revisional surgeries, with statistically significant different in comparison to
      those before the operation (P<0.05). Conclusions: There are many factors leading
      to the failure of radical mastoidectomy, including not fully opening of the
      surgical cavity , incomplete removal of the lesion tissue, poor drainage of
      surgical cavity, the lesions in the tympanic ostium of eustachian tube, and the
      improper operation procedures. Treatment strategies were taken according to above
      factors to obtain dry ear in revisional surgeries.

PMID- 29050096
TI  - [Application of three-dimensional ultrasound for diagnosis of congenital
      preauricular fistula].
AB  - Objective: To explore the application of real-time three-dimensional ultrasound
      in locating the course, the brand and the blind end of internal opening of
      congenital preauricular fistula. Methods: Congenital preauricular fistula
      patients from Changhai Hospital were studied. All the cases were evaluated using
      two-dimensional and three-dimensional ultrasound before surgeries. The surgery
      findings were utilized as the gold standard. The imaging features of 3D
      ultrasound were described to determine the accuracy of the blind end location,
      the course of the main fistula tract and the branch tracts. The diagnosis was
      compared with the surgery findings. Results: In 89 cases, among which there were
      21 branch fistulae. There were 68 bend fistulae without branch. The diagnostic
      accuracy of both two-dimensional ultrasound and three-dimensional ultrasound was
      100%. The accuracy in locating the blind end of internal opening, the course of
      the branch tracts with 3D ultrasound was 92.1%(82/89), 85.7%(18/21) , compared to
      80.9%(72/89), 57.1%(12/21) with 2D ultrasound. It was obvious that 3D ultrasound
      had more advantages. These differences were statistically significant
      (chi(2)=4.8, P<0.05; chi(2)=4.2, P<0.05). Conclusions: Compared with 2D
      ultrasound, 3D ultrasound can accurately locate the blind end of internal
      opening, the course, and the branch of preauricular fistula, clearly display the
      morphology and the spatial structure of preauricular fistulaand its surroundings.
      It has high clinical application value in preoperative imaging examination.

PMID- 29050097
TI  - [Application of computer aided design and 3D visualization technology in the
      operation of thyroid cancer with trachea invasion].

PMID- 29050098
TI  - [Sinonasal disease related to IgG4: one case report].

PMID- 29050099
TI  - [Primary malignant craniopharyngioma of infrasellar area: one case report].

PMID- 29050100
TI  - [One case report of pleomorphic liposarcoma of larynx].

PMID- 29050101
TI  - [Factors of hearing preservation in acoustic neuroma surgery].
AB  - Over the past 50 years, the focus of acoustic neuroma surgery has shifted from
      low mortality and tumor resection to retention of neurological function. Hearing
      preservation is another point in addition to facial nerve function preservation.
      Hearing preservation rates overall ranged from 2% to 93% in recent studies.
      Characteristics such as approach, pre-operative neurological function, tumor
      size, nerve of origin and fundal fluid of the internal auditory canal have been
      reported as possible influencing factors. This review provides a summary of
      recent studies and describes the prognostic factors that predict hearing
      preservation.

PMID- 29050102
TI  - [Research progress on the etiology of delayed-onset hearing loss in children].
AB  - Newborn hearing screening is an effective method for early detection of hearing
      loss, however, it is not able to detect delayed-onset hearing loss. By exploring
      the etiology of delayed-onset hearing loss in children, it can provide a clinical
      basis for early detection of delayed-onset hearing loss. Mutations in SLC26A4,
      mitochondrial, GJB2 and other genes, enlarged vestibular aqueduct, congenital
      cytomegalovirus infection, extracorporeal membrane oxygenation, and auditory
      neuropathy et al were more commonly reported risk factors. In this paper, the
      risk factors related to delayed-onset hearing loss, which are divided into 5
      categories: genetic mutation, abnormal inner ear malformation, perinatal factors,
      auditory neuropathy and no identifiable cause, are reviewed and analyzed.

PMID- 29050103
TI  - [Laryngotracheal stenosis in children].
AB  - Laryngotracheal stenosis includes congenital laryngotracheal stenosis and
      secondary laryngotracheal stenosis. Congenital laryngotracheal anomalies are
      rare, accounting for 0.3%-1.0% of all laryngotracheal stenosis(LTS). Despite the
      management of pediatric LTS over the past 30 years had been considerable
      improved, primary surgery still failed in a significant number of complex LTS
      cases. In some severe LTS cases combined with glottic stenosis, the primary
      surgery failed around 30%, even with the latest available techniques. Children
      with LTS usually need multiple operations, and need the tracheostomy tube for
      months or even years. Therefore, the etiology, clinical features, diagnosis and
      treatment of laryngotracheal stenosis are summarized in this paper.

PMID- 29050104
TI  - [Hypoglossal nerve stimulation therapy for obstructive sleep apnea hypopnea
      syndrome].
AB  - Obstructive sleep apnea hypopnea syndrome(OSAHS) is a clinical and critical
      disease to health, which the accuratly pathogenesis is not very explicit. The
      mainstream research suggested that dysfunction of upper airway dilator muscles is
      one of the hazard factors. Genioglossus innervated by the hypoglossal nerve plays
      crucial roles. It could expand volume of pharyngeal cavity, and increase airflow
      rate when stimulate it.With the development of anatomy and physiology,
      hypoglossal nerve stimulation(HGNS) entered into clinical trials, and had made
      tremendous progress since 2001. Most of clinical trials show that, it could
      dramatically improve the smooth general peculiarity of the upper respiratory
      tract in patients with OSAHS in the sleeping state.

PMID- 29050105
TI  - [The application of narrow-band imaging in diagnosis of metastatic carcinoma of
      head and neck].

PMID- 29050106
TI  - [Diagnosis and therapy for childhood solid tumor and current situation in China].

PMID- 29050108
TI  - [Evidence-based guideline on diagnosis and treatment of steroid-sensitive,
      relapsing/steroid-dependent nephrotic syndrome in children(2016)].

PMID- 29050107
TI  - [Recommendations for the diagnosis and treatment of rhabdomyosarcoma in Chinese
      children and adolescents(CCCG-RMS-2016)].

PMID- 29050109
TI  - [Interpretation of recommendations for the diagnosis and treatment of
      rhabdomyosarcoma in Chinese children and adolescents(CCCG-RMS-2016)].

PMID- 29050110
TI  - [Interpretation of evidence-based guideline on diagnosis and treatment of steroid
      sensitive, relasping/steroid-dependent nephrotic syndrome in children(2016)].

PMID- 29050111
TI  - [A long-term follow-up report of pediatric relapsed Wilms tumor after
      retreatment].
AB  - Objective: To investigate the long-term efficacy and prognostic factors of
      pediatric relapsed Wilms tumor (WT) after retreatment. Method: Sixteen children
      in Shanghai Children's Medical Center with relapsed Wilms tumor were enrolled
      consecutively in this study between April 2006 and June 2016. All patients were
      diagnosed according to pathology, imaging and medical and surgical oncologist's
      assistance. Relapse treatment included surgical excision, chemotherapy and
      selective radiation therapy. The clinical features, long-term outcomes and
      prognostic factors of patients were analyzed retrospectively.Survival data were
      analyzed by Kaplan-Meier.Log-Rank analysis was used for univariate analysis.
      Result: One case was excluded because of giving up the therapy even though no
      disease progress was identified. A total of 15 cases (5 males and 10 females)
      were included in this study. The median age at diagnosis was 3.8 years (range 0.5
      9.1 years). The tumor staging at diagnosis included one case of stageI, 7 cases
      of stageIIand 7 cases of stage III. Among cases of stage III, 6 cases had
      radiation therapy history. The pathology of all patients' recurrent tumor was
      favorable histology (FH). The median follow-up time was 34.6 months (range 12.5
      132.7 months) until March 21, 2017. The time from initial diagnosis to relapse
      was 7.9 months (range 3.1-17.9 months). Four cases experienced local recurrence,
      9 cases relapsed with metastases (6 cases in lungs, 2 in livers, 1 in
      mediastinum) and 2 cases relapsed in both local site and with metastases. Except
      to 2 cases received irregular retreatment, 13 cases received regimen I
      (doxorubicin, vincristine, epoposide and cyclophosphamide for 25 weeks) as
      relapsed chemotherapy. Five cases received autologous bone marrow transplantation
      (ABMT). Until the last follow-up, 8 cases achieved continuous complete remission
      (range 6.7-104.3 months), 3 cases had relapse again or progressing and 4 cases
      died. The estimated 5-year overall survival (OS) rate and event free survival
      (EFS) rate were (70+/-15)% and (52+/-15)%. According to whether received ABMT or
      not, the 5-year EFS rate were 51% and 53%. According to whether relapsed within 6
      months after diagnosis or not, the 5-year EFS rate were 38% and 56% respectively.
      Conclusion: The 5-year EFS rate of pediatric relapsed FH WT have reached above
      50% by multi-disciplinary treatment in our experience and we encourage patients
      and doctors to receive retreatment.

PMID- 29050113
TI  - [Long-term follow-up of neuroblastoma in children less than 18 months of age].
AB  - Objective: To assess the clinical features and long-term outcomes of
      neuroblastoma (NB) in children less than 18 months of age, so as to provide
      evidence for further improvement of treatment. Method: Clinical data(sex, age,
      stage, risk group, treatment response, follow-up, etc.) of 155 NB patients under
      age of 18 months from June 2000 to December 2015 in Shanghai Children's Medical
      Center were analyzed retrospectively. The clinical features were summarized and
      the long-term follow-up results were evaluated. The overall survival (OS) and
      event-free survival (EFS) were analyzed by using Kaplan-Meier method. Factors
      including age, stage, risk group, bone marrow and bone metastasis, N-MYC status
      and dehydrogenase(LDH) level were analyzed by Log-Rank test. Result: Totally 155
      eligible patients (96 males, 59 females) were included. The median age of disease
      onset was 7 months (11 days to 18 months). There were 31 cases of stage 1, 19
      cases of stage 2, 45 cases of stage 3, 38 cases of stage 4 and 21 cases of stage
      4S. The median follow-up time was 36 months (range 4 to 189 months), the 3-year
      and 5-year EFS rate were 89.6% and 85.2% respectively and the 3-year and 5-year
      OS rate were 96.2% and 94.1%, respectively. A total of 15 recurrent or progressed
      cases were observed. The median time to first recurrence was 11 months (range 3
      to 39 months), 6 cases eventually died. Second malignancy occurred in one
      patient. The patients who had relapsed disease within 12 months from initial
      diagnosis have much lower 3-year OS rate than those in whom the disease recurred
      12 months later (25.7% vs. 83.3%, P=0.020). Although the number of chemotherapy
      courses in median-high risk group reduced from 8.6 courses to 7.5 courses after
      the revision in 2008, the survival rate showed no significant difference between
      before and after (5-year EFS 74.4% vs. 84.3%, 5-year OS 89.0% vs. 92.9%, both
      P>0.05). In patients with stage 1 and stage 2, the 3-year EFS of 34 cases with
      surgery alone and 16 cases accepted chemotherapy were both 100%. Age at
      diagnosis, stage, risk group, MYCN status, LDH level, bone marrow involvement and
      bone infiltration had significant impacts on prognosis(all P<0.05). Conclusion:
      Satisfactory outcomes could be achieved in neuroblastoma in children aged within
      18 months; the prognosis was better in children at age less than 12 months
      compared with 12-18 months. MYCN amplification, LDH more than 5 times upper limit
      of normal range, bone marrow and bone infiltration were associated with worse
      prognosis.Excellent survival rates could be achieved in children with stage 1 and
      2 disease within 18 month's old accepted surgery alone, chemotherapy or
      radiotherapy could be avoided in these patients so as to reduce long-term adverse
      reactions.

PMID- 29050112
TI  - [Clinical pathologic characteristics and treatment outcomes of 19 relapsed
      pediatric B-cell lymphoma].
AB  - Objective: To review the clinical-pathology characteristics of 19 relapsed
      pediatric mature B cell lymphoma and to find the risk factors for recurrence and
      the feasible treatment after relapse. Method: Data of 212 pediatric B cell
      lymphomas cases in Beijing Children's Hospital from January 2006 to June 2015
      were collected retrospectively. All the patients were treated according to the B
      cell lymphoma regimen of Beijing Children's Hospital. During the study period, 19
      of 212 cases were relapsed; the clinio-pathological characteristics of relapsed
      patients before treatment and after relapse were analyzed retrospectively, the
      treatment outcomes after relapse were summarized and the patients were followed
      up. Result: Nineteen of 212 cases had relapsed disease, for these relapsed
      patients: the median age at initial diagnosis was 5.5 years old, the median level
      of uric acid was 384(range, 121-713)MUmol/L, the median level of lactate
      dehydrogenase(LDH) was 1 323(range, 146-6 370)U/L. Among 19 relapsed patients, 10
      had local relapse and 9 had multiple relapses; 17 were Burkitt's lymphoma and 2
      were diffuse large B cell lymphoma. Staging: 2 cases were stageII, 3 cases were
      stage III and 14 cases were stage IV. Risk group: 6 cases were group B and 13
      cases were group C. Nine cases had bone marrow involvement and 10 cases had
      central nervous system(CNS) involvement. Acute tumor lysis syndrome was seen in 6
      cases during the early treatment and 13 cases had delayed treatment. Treatment
      after relapse: 10 cases received further treatment after relapse (rituximab + 1-4
      courses high intensity second-line chemotherapy), 3 cases received autologous
      stem cell transplantation. There was no chemotherapy or infection related death,
      3 cases achieved complete remission (CR). For all the 212 patients, the median
      follow-up time was 47 (range, 1-131)months and the 5-year event free
      survival(EFS)rate was (89.4+/-0.2)%. For the 19 relapse cases, the 5-year overall
      survival (OS) rate was (21.1+/-0.1)%, CR rate after relapse was 30%, patients
      died of the progression of the primary disease, no treatment related death
      occurred. Univariate analyses showed that bulky disease, stage IV, maxillofacial
      and CNS involvement, LDH>1 000 U/L, delay treatment, day 7 evaluation shrink
      <25%, residual diseases after 3 months treatment are relapse risk factors (all
      P<0.01). Conclusion: Patients relapse during the treatment or at the early stage
      after the end of all chemotherapy have poor prognosis. So far there is no
      effective method for early relapse patients; the late relapse patients had the
      possibility of CR if they are sensitive to salvage treatment. In conclusion, to
      improve the outcome, the key point is to reduce the relapse.

PMID- 29050114
TI  - [Effect of interferon-gamma on airway inflammation following respiratory
      syncytial virus reinfection in mice].
AB  - Objective: To identify the role of interferon (IFN)-gamma during respiratory
      syncytial virus (RSV) re-infection in mice. Method: Female wild type C57BL/6 mice
      and IFN-gamma knockout mice (IFN-gamma(-/-) mice) at the age of 6 to 8 weeks were
      randomly divided into two groups: control group and RSV group, according to
      random number table.Each group was further divided into primary infection group
      and re-infection group.There were 8 groups.Mice were sacrificed on days 5, 7, 14
      to collect samples.There were 5-8 mice in each group at each time point.And
      experiment was repeated twice. Leukocytes in bronchoalveolar lavage fluid (BALF)
      were counted, left lung tissues were stained with HE and histopathological
      scoring (HPS) was performed.The concentrations of IFN-gamma, IL-5, IL-13 were
      determined with ELISA.T test or single factor analysis of variance was used to
      compare between groups. Result: (1) Mice infected or reinfected with RSV showed
      pale hair, weight loss, decreased activity and anorexia.(2) IFN-gamma levels
      significantly increased on days 5 and 7 following RSV primary infection and
      reinfection as compared to control groups in wild type mice ((192+/-44) vs.(36+/
      8) and (531+/-161) vs.(23+/-4) pg/ml on day 5, (100+/-23) vs.(36+/-8) and (862+/
      186) vs.(23+/-4) pg/ml on day 7, t=2.654, 2.513, 2.654, 3.968, all P<0.05). (3)
      Compared to the RSV-reinfected IFN-gamma(-/-) mice, RSV-reinfected wild type mice
      had less body weight loss ((13.6+/-2.6)% vs.(22.7+/-2.9)% on day 5, (18.0+/-3.1)%
      vs.(26.5+/-1.8)% on day 7, t=2.314, 2.308, both P<0.05), lower lung tissue
      histopathological score ((1.50+/-0.09) vs.(2.07+/-0.11) on day 5, (1.53+/-0.11)
      vs.(2.08+/-0.09) on day 7, (1.10+/-0.06) vs.(1.59+/-0.08) on day 14, t=3.916,
      3.890, 4.837, all P<0.01), less BALF inflammatory cells count ((11.6+/-2.0)
      vs.(44.2+/-10.6)*10(5)/ml on day 5, (18.2+/-3.9) vs.(38.3+/-2.2)*10(5)/ml on day
      7, t=2.818, 4.786, both P<0.05), and lower levels of IL-5 and IL-13 ((24+/-3)
      vs.(148+/-23), (23+/-4) vs.(169+/-26) pg/ml on day 5, (30+/-8) vs.(233+/-44),
      (20+/-5) vs.(182+/-19) pg/ml on day 7, (91+/-6) vs.(129+/-19), (62+/-8) vs.(132+/
      5) pg/ml on day 14, t=5.252, 5.445, 4.517, 7.326, 3.816, 7.577, all P<0.01).
      Conclusion: IFN-gamma can alleviate airway inflammation following RSV reinfection
      in mice.

PMID- 29050115
TI  - [Effects of ovalbumin exposure during pregnancy of mice on the ovalbumin re
      exposure in adult progeny].
AB  - Objective: To observe the immunoreaction of offspring mice by ovalbumin (OVA) re
      exposure after their mothers exposed to OVA during pregnancy. Method: A
      prospective controlled study was conducted to observe mice after repeated OVA
      exposures at 6-8 weeks.Their mothers were exposed to OVA during different stages
      of pregnancy.The symptoms were recorded and scored.The levels of OVA-specific IgE
      in serum, interferon-gamma(IFN-gamma) and interleukin-4(IL-4) in supernatant of
      spleen primary lymphocytes in vitro were measured by ELISA.The results were
      analyzed by single factor analysis of variance or rank sum test. Result: All the
      mice in each group had acute diarrhea.The diarrhea happened earliest (2 days) and
      most severe in the late pregnancy group (early pregnancy group 7.0+/-1.0; middle
      pregnancy group: 7.1+/-1.1; late pregnancy group: 9.9+/-2.2, P<0.01). The levels
      of absorbance of OVA-specific IgE in the pregnancy groups were higher than those
      of the control group.The absorbance of OVA-specific IgE in late pregnancy group
      was the highest (control: 0.27+/-0.06; early pregnancy group: 0.51+/-0.13; middle
      pregnancy group: 0.50+/-0.09; late pregnancy group: 0.63+/-0.13, P<0.01). There
      was no significant change in IFN-gamma expression in cultured supernatant of
      spleen lymphocytes in each group (control: (133+/-7) pg/ml; early pregnancy
      group: (133+/-4) pg/ml; middle pregnancy group: (134+/-6) pg/ml; late pregnancy
      group: (132+/-4) pg/ml, all P value >0.05). The expression of IL-4 in the
      experimental groups was higher than that in the control group, especially in late
      pregnancy group(control: (25.3+/-2.4) pg/ml; early pregnancy group: (32.4+/-4.4)
      pg/ml; middle pregnancy group: (35.0+/-5.4) pg/ml; late pregnancy group: (47.1+/
      5.8) pg/ml; P value all<0.01). Conclusion: The allergic reaction of the OVA re
      exposure progeny whose mothers were exposed to OVA in the late pregnancy period
      was most severe, suggesting that late pregnancy period might be the high risk
      stage of intrauterine sensitization, or"window period".

PMID- 29050116
TI  - [Correlation study of blood drug concentration and nephrotoxicity on high dose
      methotrexate therapy in suggestion of diagnosis and treatment of childhood acute
      lymphoblastic leukemia in the 4th revised edition].
AB  - Objective: To explore the influence of the 4th revised treatment recommendations
      in childhood acute lymphoblastic leukemia (ALL) on high dose methotrexate(HD-MTX)
      induced nephrotoxicity and MTX blood concentrations. Method: The clinical data
      from 330 ALL children who received 1 242 courses of HD-MTX therapies from
      September 2012 to November 2016 was collected. The courses were divided into two
      groups based on the chemotherapies: original scheme group was treated with the
      3rd revised regimen, and new scheme group was treated with the 4th revised
      regimen. The two groups in acute kidney injury (AKI) and MTX blood concentrations
      were compared. Result: The incidences of AKI with low risk (LR) and intermediate
      risk (IR) in new scheme group were significantly lower than those in original
      scheme group (1.3%(3/229) vs. 7.9%(24/303), 4.9%(10/204) vs. 12.8%(26/203),
      chi(2)=11.831 and 7.888 respectively, both P<0.05). There was no significant
      difference in the incidence of AKI with high risk (HR) in the two groups
      (15.2%(10/66) vs. 10.5%(25/237), chi(2)=1.071, P>0.05). The 48h MTX blood
      concentrations and the interphase from onste to MTX concentrations decreased to
      the safe level with LR and IR children in new scheme group were significantly
      lower than those in original scheme group (0.36(0.08-4.00) vs. 0.44(0.06-32.00)
      MUmol/L, 0.49(0.22-33.00) vs. 0.60(0.18-83.00) MUmol/L, 3(2-6) vs. 3(2-11) d, 3(2
      11) vs. 3(2-19) d, Z=-5.953, -2.658, -4.490 and -4.729 respectively, all P<0.05).
      The differences with HR were not observed between the two groups (0.61(0.14
      36.00) vs. 0.71(0.11-68.00) MUmol/L, 3(2-15) vs. 3(2-13) d, Z=-1.465 and -1.179
      respectively, both P>0.05). Conclusion: Decreased renal toxicity and acceleration
      of MTX excretion may occur when childhood ALL with LR and IR were treated with
      the 4th revised regimen. However, nephrotoxicity and MTX blood concentrations
      have no significant differences with HR in the two regimens, and close monitoring
      are necessary.

PMID- 29050117
TI  - [Pediatric idiopathic hypereosinophilic syndrome with pulmonary embolism: a case
      report and review of literature].
AB  - Objective: To explore clinical features of idiopathic hypereosinophilic syndrome
      combined with pulmonary embolism. Method: A retrospective analysis of a patient
      with idiopathic hypereosinophilic syndrome and pulmonary embolism diagnosed and
      treated in the Respiratory Department of Shanghai Children's Hospital in
      September 2016 was performed. A literature search was performed with"Eosinophils
      increased, thrombosis"as the Chinese keywords in Wanfang database and"idiopathic
      hypereosinophilic syndrome, deep vein thrombosis"as the English key words in
      PubMed database. The time interval was from April 1985 to March 2017. Result: The
      patient was 11-year-old with fever and cough. Computed tomography angiography
      (CTA) showed pulmonary embolism, inferior vena cava thrombosis. Ultrasound
      examination of the left leg demonstrated venous thrombosis. Complete blood count
      showed eosinophilia and thrombocytopenia. Literature found 30 articles, including
      eighteen case reports, twelve reviews and other types of articles. A total of 23
      cases were reported, only three were pediatric cases. According to the literature
      that eosinophilia can damage the vascular epithelium, leading to multiple
      arterial and venous thromboses, anticoagulation and glucocorticoid treatments are
      effective. Conclusion: The diagnosis of idiopathic hypereosinophilic syndrome is
      complicated. It may cause multiple thromboses. Anticoagulation and
      glucocorticoids can reduce eosinophil count and decrease its toxins which can
      injure vascular endothelium. The effectiveness of preventative anticoagulant
      therapy is unclear and requires further clinical study.

PMID- 29050118
TI  - [Gene mutation and clinical phenotype analysis of patients with Noonan syndrome
      and hypertrophic cardiomyopathy].
AB  - Objective: To analyze the gene mutations and clinical features of patients with
      Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation
      domain in five cases diagnosed with Noonan syndrome and hypertrophic
      cardiomyopathy and identified the relationship between the mutant domain and
      hypertrophic cardiomyopathy by searching relevant articles in pubmed database.
      Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome
      1 and RAF1 gene in chromosome 3) in five cases all had been reported to be
      related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy
      relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients
      with same gene mutation had different clinical manifestations. Both case 4 and 5
      had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild
      pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion:
      Noonan syndrome is a genetic heterogeneity disease. Our study identified specific
      gene mutations that could result in Noonan syndrome with hypertrophic
      cardiomyopathy through molecular biology methods. The results emphasize the
      importance of gene detection in the management of Noonan syndrome.

PMID- 29050120
TI  - [SEPN1 related myopathy manifested as sleep-related hy poventilation].

PMID- 29050121
TI  - [Research progress in postnatal glucocorticoid for the therapy of
      bronchopulmonary dysplasia].

PMID- 29050119
TI  - [Feasibility of domestic (18)F-DOPA PET/CT scanning in the differential diagnosis
      of pancreatic lesions in children with hyperinsulinemic hypoglycemia].
AB  - Objective: To study the feasibility of (18)F-fluoro-L-dihydroxyphenylalanine
      positron emission tomography/Computed tomography ((18)F-DOPA PET/CT) scanning in
      the localization and differential diagnosing of focal versus diffuse form of
      pancreas lesions in patients with hyperinsulinemic hypoglycemia (HH). Method:
      Twenty-four patients were diagnosed with HH between January, 2016 and February,
      2017 in the Department of Pediatric Endocrinology and Inherited Metabolic
      Diseases, Children's Hospital of Fudan University using an integrated clinical
      and biochemical diagnostic protocol, domestic (18)F-DOPA PET/CT imaging technique
      were applied after MRI and ultrasound failed to detect pancreas lesions. Pancreas
      (18)F-DOPA standardized uptake values (SUV) were measured, and pancreas' lesions
      were dually analyzed via visual method and pancreas percentage SUV method. Among
      these patients, 9 patients received surgical pancreatic lesion resections, the
      correlations among surgical outcomes, histopathological findings and (18)F-DOPA
      PET/CT scan results were analyzed. Result: Seven patients were detected with
      focal form of pancreas lesions, the mean peak of SUV was 4.7+/-1.7(2.6-7.1), and
      17 patients were found to have diffuse form lesions after (18)F-DOPA-PET/CT
      scanning. Among the 24 cases, 9 patients (7 showed focal and 2 showed diffuse
      (18)F-DOPA PET/CT pancreatic uptake)were euglycemic without any medical support
      after surgery; the resected pancreatic tissue histopathological results were
      consistent with that of PET/CT imaging. Only one patient, who responded to
      medical treatment before surgery, had temporary hyperglycemia after operation.
      Conclusion: Domestic (18)F-DOPA PET/CT could successfully locate and
      differentiate the pancreatic lesions and thus improve the success of surgery.

PMID- 29050122
TI  - [Radiation protection in pediatric interventional procedures of congenital heart
      diseases].

PMID- 29050124
TI  - [Introduction of drug-induced interstitial lung disease].

PMID- 29050123
TI  - [Enhance the importance and knowledge of drug-induced lung injury].

PMID- 29050125
TI  - [Key point of lung transplantation for interstitial lung disease].

PMID- 29050126
TI  - [Clinical analysis of rituximab-induced interstitial lung disease].
AB  - Objective: To investigate the clinical characteristics, diagnosis-treatment
      points and prognosis of rituximab-induced interstitial lung disease (R-ILD), and
      to improve the recognition of this disease. Methods: The clinical data on 4 cases
      of R-ILD were analyzed retrospectively, and the related literatures were
      reviewed. The literature review was carried out respectively in Wanfang Data,
      CNKI and PubMed by October 2016 with"rituximab"and"interstitial lung
      disease"or"interstitial pneumonitis"as the search terms. Results: The all 4
      patients received chemotherapy including rituximab, had respiratory symptoms
      after 2 to 5 cycles chemotherapy respectively. The chest computerized tomography
      findings of all 4 cases showed diffuse ground glass opacities. In all of the
      patients, the diagnosis of R-ILD was made and glucocorticoids therapy was
      initiated. After treatment, the clinical symptoms improved promptly and follow-up
      chest computerized tomography showed pulmonary lesions significantly resolved.
      Literature review found 48 articles (2 reviews, 6 original articles, 39 case
      reports and 1 other article) . 50 cases of R-ILD were collected and the chief
      complaint were dyspnea, cough and fever. The ground-glass pattern on the CT scan
      of the chest was the important feature of this disease. Therapy included
      glucocorticoids, discontinuation of rituximab, and any other clinically necessary
      measures. Conclusions: Rituximab can cause interstitial lung disease. The
      diagnosis relies on clinical manifestation and radiological findings. The good
      prognosis depends on prompt discontinuation of rituximab and treatment with
      glucocorticoids.

PMID- 29050127
TI  - [Immune-related pneumonitis caused by programmed death-1 inhibitor Pembrolizumab:
      a case report and literature review].
AB  - Objective: To investigate the risk factors, clinical manifestations, radiological
      features, diagnosis, treatment and prognosis of immune-related pneumonitis caused
      by programmed death-1(PD-1)/PD-L1 inhibitors. Methods: The clinical data of
      immune-related pneumonitis caused by PD-1 inhibitor Pembrolizumab in a patient
      with advanced esophageal carcinoma admitted to the 307(th) Hospital of Chinese
      People's Liberation Army was retrospectively analyzed and the related literatures
      were reviewed. We searched Medline database using the keywords"PD-1
      inhibitor","PD-L1 inhibitor","Pembrolizumab","Nivolumab","Atezolizumab"combined
      with"Pneumonitis"by Mar 31, 2017. Results: The patient was a 60-year-old male
      presented with progression disease after surgery, local radiation and couples of
      chemotherapy for his esophageal carcinoma. Then pembrolizumab, a kind of PD-l
      inhibitors, was given intravenously every 3 weeks with the average dosage 3 mg
      per kg. After six cycles of pembrolizumab, the patient began to have fever, cough
      and dyspnea, which aggravated gradually. Chest CT showed diffuse ground glass
      opacity, exudation and consolidation in both lungs and little pleural effusion in
      the right side. Cellular interstitial pneumonitis was confirmed by pathological
      examination. The patient's symptoms were alleviated after enough steroids and
      chest CT showed pulmonary infiltration was also absorbed. But the pneumonitis
      reoccurred twice after stopping or tapering steroids quickly and could also be
      controlled by using steroids again. Now the patient was still given steroids
      treatment and the primary esophageal cancer remained stable. 14 articles were
      retrieved and 88 cases of immune-related pneumonitis caused by PD-1/PD-L1
      inhibitors were reported. Among these 89 cases with immune-related pneumonitis,
      both male and female could attack and the median age was 67 years old. Most cases
      were grade 1 or 2. The common clinical manifestations were dyspnea, cough, fever
      and other immune-related damages. And about 20% patients had no symptoms. Ground
      glass opacities, reticular opacities, consolidation and centrilobular nodules
      were the common radiological features. The commonest histologic pattern of
      pneumonitis associated with anti-PD-1/PD-L1 therapy on lung biopsy was organizing
      pneumonia. Adequate steroid and tapering slowly is the standard treatment.
      Immunosuppressive agents could be added in some serious cases. The prognosis was
      relatively good. Most patients were alleviated but few patients died of
      progression disease or infections during treatment. Conclusions: Immune-related
      pneumonitis associated with PD-l/PD-L1 inhibitor should be aware of; early
      detection, early treatment, and the prognosis could be better.

PMID- 29050128
TI  - [Lung transplantation for connective tissue disease-associated interstitial lung
      disease recipient].
AB  - Objective: To investigate the timing and complications of lung transplantation
      for the treatment of connective tissue disease-associated interstitial lung
      disease (CTD-ILD). Method: The clinical data of connective tissue-associated
      disease lung transplantation recipients from September, 2015 to February, 2017
      were collected. Results: 11 patients with CTD-ILD were evaluated by lung
      transplantation and were treated with lung transplantation. Including 2 cases
      dermatomyositis/polymyositis and interstitial lung disease (PM/DM-ILD), 4 cases
      rheumatoid arthritis and interstitial lung disease (RA-ILD), 4 cases of primary
      Sjgren's syndrome and interstitial lung disease (pSS-ILD), 1 case of systemic
      sclerosis and interstitial lung disease (SSc-ILD). There are 6 cases are CTD-ILD
      PAH patients of all. There were 5 males and 6 females, aged 37-70 years, with an
      average age of (52.73+/-9.53) years. 7 patients received single lung
      transplantation, 4 patients received double lung transplantation. 3 patients died
      in the early postoperative period, one for pulmonary embolism, one for septic
      shock and heart failure, one for severe primary graft failure (PGD). The
      remaining patients were followed up (4-24 months) with good survival, no acute
      and chronic rejection and other complications were observed. The survival rate
      was similar to that of other disease sources. Conclusion: There is no recurrence,
      acute and chronic rejection and other complications were observed in CTD-ILD
      and/or PAH lung transplant recipients. And the survival rate was comparable to
      that of other disease sources.Lung transplantation is a safe and effective choice
      for selected CTD-ILD patients.

PMID- 29050129
TI  - [Anomalous systemic arterial supply to normal basal segments of the lower lobe:
      three cases reports and literature review].
AB  - Objective: To improve the clinical recognition of anomalous systemic arterial
      supply to normal basal segments of the lower lobe in clinical manifestations,
      diagnosis and treatment. Methods: Three cases were presented and related
      literatures were reviewed. A literature review was performed with"anomalous
      systemic arterial supply to normal lower lobe of the lung","anomalous systemic
      arterial supply to normal basal segments of the lower lobe"and"anomalous systemic
      arterial supply to normal basal segments of the left lower lobe of the lung"as
      key words in Pubmed, Embase, Ovid, Wanfang database and CNKI. Result: Our 3 cases
      were male, with an average age of 36 years old; all of them were admitted with
      hemoptysis. Left lower lobectomy was performed in 2 cases, and the other 1 case
      underwent endovascular embolization. 26 related articles were retrieved and our 3
      cases were included in this study with a total of 57 cases. The ratio of male to
      female was 2?1 (38?19), with an average age of about 35 years old. The most
      common symptom was hemoptysis (26/57), followed by asymptomatic (22/57). The main
      treatments included left lower lobectomy (17/47) and endovascular embolization of
      anomalous systemic artery (13/47). Conclusions: This disease is more common in
      male, and the most common symptom is hemoptysis. When chest CT scan shows a
      nodular retrocardiac density with hemoptysis symptom, clinicians and radiologists
      should raise suspicion of anomalous systemic arterial supply to normal basal
      segments of the lower lobe. Chest contrast-enhanced CT scan is an appropriate
      imaging method to confirm diagnosis. The main treatments include left lower
      lobectomy and endovascular embolization. For asymptomatic patient, observation
      may be an acceptable option.

PMID- 29050130
TI  - [Evaluation of a high-intensity fluorescent fluorophage method for diagnosis of
      drug-resistance in tuberculosis].
AB  - Objective: To evaluate the high-intensity green fluorescent protein fluorophage
      Phi(2)GFP10 method for drug susceptibility testing of tuberculosis for
      isoniazid(INH), rifampin(RIF), and streptomycin(SM). Methods: A total of 128
      clinical M. tuberculosis strains were isolated from patients with suspected drug
      resistant tuberculosis visiting Beijing Chest Hospital (Beijing, China) from
      April to June 2014.All of the isolates were tested by the phage assay, while
      conventional drug susceptibility tests were performing on Lwenstein-Jensen
      culture medium as reference. Results: The sensitivities of Phi(2)GFP10 assay for
      INH, RIF, and SM resistance detection were 100.0%, 98.1%(53/54), and
      92.6%(50/54), respectively, while their specificities were 84.8%(56/66),
      91.9%(68/74), and 91.9%(68/74), respectively. The agreement between the phage
      assay and the conventional assay for detecting INH, RIF, and SM resistance was
      0.92, 0.95 and 0.92, respectively. The Phi(2) GFP10-phage assay could be done
      within 2 days for RIF and SM, and 3 days for INH. Conclusions: The Phi(2)GFP10
      phage method for drug susceptibility test is very sensitive and specific. The
      method has the potential to be a valuable, rapid and economical screening method
      for detecting drug-resistant tuberculosis.

PMID- 29050131
TI  - [Desquamative interstitial pneumonia: report of one case and review of
      literature].
AB  - Objective: To analyze the clinical features, diagnosis, and treatment of
      desquamative interstitial pneumonia(DIP). Methods: The clinical manifestation,
      radiology, and pathology were analyzed in one patient with DIP in Beijing
      Hospital following review of the literatures. Results: The patient was a 55-year
      old male presented with cough, shortness of breath and hypoxemia.Previous history
      of smoking and exposure to a variety of metals. A CT scan of the chest revealed
      diffuse ground-glass densities. A diagnosis of desquamative interstitial
      pneumonia (DIP) was confirmed by a thoracoscopic open lung biopsy. After
      treatment with hormone, the condition improved.A total of 66 cases were included
      in this study, the smoking groupof 20 cases, non-smokers of 46 cases.The smoking
      group was older than the non-smoking group [(47.5+/-12.1)years vs (26.1+/-22.5)
      years]; the present of chest pain, shortness of breath(4/20 vs 0/46; 8/20 vs
      3/46) was higher in smoking group than in non-smoking group, and ground glass
      opacity in the chest image(15/20 vs 20/46) was also higher in smoking group than
      in non-smoking group.Pulmonary function showed more diffuse dysfunction(12/14 vs
      6/13) in smoking group than in non-smoking group. Conclusions: As a rare
      disorder, DIP is associated with current or former cigarette smoking and many
      other risk factors. The clinical presents of non-smoker is atypical.DIP is
      curable to glucocorticoid and has a good prognosis.There is a possible of
      recurrence.

PMID- 29050133
TI  - [Research progress in the mechanism of hyponatremia caused by Legionella
      pneumonia].

PMID- 29050134
TI  - [The role of nemonoxacin in the treatment of community acquired pneumonia].

PMID- 29050132
TI  - [The timing and prognosis of lung transplantation for chronic sarcoidosis].

PMID- 29050135
TI  - [Research progress of biodegradable trachea stent].

PMID- 29050137
TI  - [The application and signiflcance of CO(2) monitoring in sleep related breathing
      disorders].

PMID- 29050136
TI  - [Classification and surgery of chronic pulmonary aspergillosis].

PMID- 29050138
TI  - [Standardization of diagnosis and treatment of urinary infection in the female,
      maintenance of female physical health and well-being].

PMID- 29050139
TI  - [To promote a comprehensive development of precise medical research in pulmonary
      thromboembolism].

PMID- 29050141
TI  - [The era of ischemia-free organ transplantation is coming].

PMID- 29050140
TI  - [Antithrombotic therapy of pulmonary embolism: a painstaking investigation in
      front of the complex underlying diseases and clinical settings].

PMID- 29050142
TI  - [The genetics of pulmonary thromboembolism].

PMID- 29050143
TI  - [Characteristic biomarkers in acute pulmonary thromboembolism].

PMID- 29050144
TI  - [Embolic burden assessment in pulmonary thromboembolism diagnosis and treatment].

PMID- 29050145
TI  - [Genotype-guided dosing of warfarin in VTE anticoagulation].

PMID- 29050146
TI  - [Metabolism genes and pharmacogenetics of non-vitamin K antagonist oral
      anticoagulants].

PMID- 29050147
TI  - [Association of vitamin D receptor gene polymorphisms with idiopathic
      hypoparathyroidism phenotypes].
AB  - Objective: To explore the association of vitamin D receptor (VDR) gene
      polymorphisms with idiopathic hypoparathyroidism (IHP). Methods: Two hundred and
      three patients with IHP and 209 healthy age- and sex-matched subjects were
      recruited at Peking Union Medical College Hospital between December 1987 and
      December 2015 as case group and control group, respectively. The VDR gene
      polymorphisms including rs739837, rs3847987 and rs2228570 were analyzed by
      Sequenom Mass Array. The frequency of different genotypes and alleles was
      detected, then their association with pathogenesis of IHP was analyzed. The
      clinical characteristics, biochemical indicators were collected to explore the
      genotype-phenotype relationship. The role of reactions to vitamin D treatment
      were compared between patients with different genotypes. Results: There was no
      significant difference in the genotypes and allele frequency distribution of SNPs
      between the two groups (all P>0.05). However, in the initially-treated patients,
      the genotypes of rs739837 were related to serum calcium level (r=0.186, P=0.026).
      And patients with GG genotype of rs2228750 had higher level of urine calcium than
      GA and AA (277.7 mg vs 141.1 mg, P=0.024) after treating with oral vitamin D(3)
      and calcium. Conclusions: Functional SNPs of VDR gene including rs739837,
      rs3847987 and rs2228570 might be irrelevant to the pathogenesis of IHP. But the
      genotypes of rs739837 were related to serum calcium level, and rs2228570 may have
      an effect on the different responses to vitamin D and its analogues in IHP
      patients.

PMID- 29050148
TI  - [The analysis of risk factors and outcomes of carotid endarterectomy for carotid
      artery stenosis].
AB  - Objective: To evaluate the early and long-term outcomes of carotid endarterectomy
      for carotid artery stenosis and analyse the risk factors for the outcomes.
      Methods: A retrospective review of 369 patients underwent carotid
      endarterectomy(CEA) in Peking Union Medical College Hospital from Oct 2006 to Nov
      2012 was conducted. Clinical data including general conditions, perioperative and
      follow-up outcomes were collected. Results: Three hundred sixty-nine patients
      underwent 407 CEAs. The long-term follow-up rate (>=30 d) was 89.9% and follow-up
      period was 11.8-48.3 months. Among 407 CEAs, patients with symptomatic carotid
      artery stenosis, carotid stenosis over 70% and contralateral severe carotid
      stenosis occupied 78.0%(317/407), 98.4%(400/407) and 12.04%(49/407) respectively.
      Total early complications (<30 d) of stroke, cardiac events and death was 3.93%
      (16/407). Univariate analysis showed no risk factor had significant effect on
      early complications (P>0.05). Total long-term complications of stroke, cardiac
      events and death was 8.7% (32/366). Univariate analysis showed that total long
      term complication rate of smoking group was higher than non-smoking group (12.1%
      vs 5.1%, P<0.05), contralateral carotid artery stenosis group was higher than
      opposite one (28.6% vs 8.0%, P<0.05). Multivariate Logistic regression showed the
      HR of long-term complications rate in patients aged over 65 years, smoking
      history, myocardial infarction and contralateral carotid stenosis were 2.59,
      2.66, 2.48 and 6.06, respectively. Conclusions: CEA is safe method for the
      treatment of carotid stenosis. To CEA, age over 65 years, smoking history,
      myocardial infarction and contralateral carotid stenosis are risk factors for
      long-term adverse outcomes.

PMID- 29050149
TI  - [Accuracy analysis and comparison of different serological detection methods in
      syphilis].
AB  - Objective: To compare the accuracy of different methods by reviewing syphilis
      serologic screening external quality assessment (EQA) data of Chinese primary
      health care institutions. Methods: The EQA was based on one or two distinct
      shipments from 2011 to 2016. Each shipment consisted of five serum samples. The
      laboratories performed the EQA and sent back the results by the deadline. The
      results were analyzed using the standard procedures and methods. Results: Six
      different methods were used for syphilis serologic screening: enzyme linked
      immunosorbent assay, colloidal gold method, Treponema pallidum particle
      agglutination (TPPA) test, rapid plasma reagin card test, toluidine red unheated
      serum reagin test and chemiluminescence immunoassay. From 2011 to 2016, the
      qualified rate of the colloidal gold method and TPPA had improved from 67.78% to
      98.89% and 27.27% to 100%, respectively. The positive coincidence rate of TPPA
      had changed from 54.55% to 100%. The negative coincidence rate of TRUST had
      changed from 78.95% to 100%. Conclusions: There were differences between
      different methods of syphilis serological detection. With the implementation of
      the EQA performance, the qualified rate, positive coincidence rate, and negative
      coincidence rate were improved in the primary maternal and child health care
      institutions.

PMID- 29050150
TI  - [Diagnostic value analysis of capsule endoscopy in obscure gastrointestinal
      bleeding patients of different ages].
AB  - Objective: To evaluate the diagnostic value of capsular endoscopy in patients
      with obscure gastrointestinal bleeding (OGIB) in different age groups, and assess
      its effectiveness and safety. Methods: A total of 216 patients who were diagnosed
      with OGIB between March 2005 and March 2016 at Department of Gastroenterology of
      Peking Union Medical College Hospital were retrospectively reviewed. They were
      assigned into three groups: young adults, middle-aged and elderly. The
      demographic characteristics, clinical manifestations, working performance as well
      as endoscopic features in each group were collected and analyzed. Results: The
      detection rate and diagnosis rate of the young adults and middle-aged group were
      98.53% vs 98.51% (P=0.992), 92.65% vs 91.04% (P=0.734), while those between the
      young adults and the elderly group were 98.53% vs 91.14% (P=0.109), 92.65% vs
      87.34% (P=0.289), and 98.51% vs 91.14% (P=0.113) and 91.04% vs 87.34 (P=0.475)
      between the middle-aged and elderly group. No significant difference existed in
      either detection rates nor diagnostic rates between the different age groups. The
      distribution of the small intestinal lesions varied between the different age
      groups. The top three common lesions in young adults were vascular malformation,
      small intestine ulcer and Crohn's disease, while in the middle-aged group
      vascular malformation, non-specific enteritis and small intestine ulcer were the
      most common. Patients in elderly group were most likely to have vascular
      malformation, small intestine ulcer and erosion. Conclusions: For patients of any
      age with OGIB, capsule endoscopy is a safe, effective and comfortable examination
      which can be widely used in clinical practice.

PMID- 29050152
TI  - [Effect of transcription factor E2F1 expression on the invasion of prostate
      cancer].
AB  - Objective: To investigate the effect of transcription factor E2F1 on the invasion
      of prostate cancer and its clinical significance. Methods: A stable inhibition of
      E2F1 prostate cancer cell line PC3 was established. The E2F1 and relative
      invasion biomarker protein expression level of the transfected cells was detected
      by Western blot. The PC3 cells were divided into two groups: the control group
      and sh-E2F1 group, cell invasion assay and cell scratch test were used to detect
      the number of cell migration in the experiment time. The relationship between
      E2F1 mRNA expression level and clinical prognostic parameters was analyzed
      through microarray data of prostate cancer. Results: E2F1 inhibited PC3 cell line
      was constructed successfully. The results of Western blot showed that the
      expression of Vimentin, CD147, MMP-2 and MMP-9 protein in E2F1 suppression group
      was lower than those in control group, while the protein expression of E-cadherin
      increased. Compared to the control group, inhibiting the expression of E2F1 in
      prostate cancer cells significantly decreased the invasion and migration, with
      significant difference (P<0.05). High mRNA expression of E2F1 decreased
      biochemical recurrence rate and overall survival rate after surgery (P=0.047,
      0.035), and the E2F1 expression level was related to pathological stage of
      prostate cancer. Gleason score and tumor metastasis (P<0.05). Conclusion: E2F1
      enhances the invasion and metastasis of prostate cancer through a variety of
      mechanisms, and its expression level has an important relationship with the
      adverse prognosis of patients with prostate cancer.

PMID- 29050151
TI  - [Relationship between Helicobacter pylori infection and miR-24-3p expression
      during the development of gastric mucosa lesions].
AB  - Objectives: To explore the expression of micro RNA-24-3p (miR-24-3p) in different
      gastric mucosa lesions, and analyze the potential correlation between
      Helicobacter pylori (H.pylori) infection and miR-24-3p expression in different
      gastric lesions. Methods: 158 gastric biopsy specimens were divided into four
      groups, including 35 chronic superficial gastritis (CSG) samples, 43 chronic
      atrophic gastritis (CAG) samples, 41 intestinal metaplasia (IM) samples and 39
      dysplasia (Dys) samples. Those samples were collected from patients undergoing
      gastroscopy at the Department of Gastroenterology, Aerospace Center Hospital,
      from September 2005 to June 2012. The expression of miR-24-3p was detected using
      in situ hybridization. H. pylori infection status was determined by rapid urease
      test and Warthin-Starry stain. Results: Higher expression rate of miR-24-3p was
      observed in CSG compared with those in CAG, IM and Dys, respectively. The miR-24
      3p expression rate in CSG with H. pylori infection was significantly lower than
      that without H. pylori infection (P=0.001), but it was not observed in CAG, IM
      and Dys groups (all P>0.05). Conclusions: MiR-24-3p was highly expressed at the
      early stage of gastric mucosal lesion. Attenuation of miR-24-3p expression is
      associated with the development of severe gastric mucosa lesions. H. pylori may
      play a role in miR-24-3p regulation in the early stage of gastric mucosa lesions.

PMID- 29050153
TI  - [Study on the differentiation of rat bone marrow mesenchymal stem cells into
      chondrocytes induced by TGF-beta 3].
AB  - Objective: To explore the methods for the differentiation of rat bone marrow
      mesenchymal stem cells (BMMSCs) into chondrocytes induced by transforming growth
      factor (TGF)-beta 3 in vitro, and search for a reliable seed cell for the
      regeneration and repair of articular cartilage in osteoarthritis. Methods: SD rat
      femoral and tibial BMMSCs were cultured by the whole bone marrow adherent method,
      and then the purity was identified by flow cytometry. P3 generation cells were
      induced and differentiated into chondrocytes by the induction of differentiation
      medium containing TGF-beta 3, and cell chondrogenic differentiation ability at
      different induction time points was detected. Results: The primary and passage
      cultured BMMSCs were spindle-shaped, and partly triangular. After passage, the
      proliferation rate of P3 generation cells was fast, like the growth of fish shoal
      or eddy. After chondrogenic induction, the cells were polygonal and triangular in
      the form of cluster growth, which was similar to chondrocyte morphology, and the
      cell proliferation was decreased. Immunofluorescence staining and Western
      blotting method showed that the cells had a large number of col II fluorescent
      expression, and cells and extracellular matrix was stained blue by Alcian blue
      staining, with no significant difference at day 7 and day 14. After using Wnt
      signal blocker, col II protein expression was significantly reduced, with
      statistically significant difference (P<0.05). Conclusion: TGF-beta 3 can rapidly
      induce the differentiation of BMMSCs into cartilage cells, which provides a good
      carrier for BMMSCs transplantation and the repair of articular cartilage, and
      thus to treat osteoarthritis.

PMID- 29050154
TI  - [The innovation of international consensus guidance for management of myasthenia
      gravis(2016) and its practice in China].

PMID- 29050155
TI  - [Correlation factors of 127 times pre-crisis state in patients with myasthenia
      gravis].
AB  - Objective: To investigate the clinical features of the Pre-Crisis State and
      analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis.
      Methods: We included 93 patients with myasthenia gravis (MG) who experienced 127
      times Pre-Crisis State between October 2007 and July 2016. Those patients were
      hospitalized in the MG specialize center, Department of Neurological Science,
      first Affiliated Hospital of Sun Yat-sen University. The information of the
      general situation, the clinical manifestations and the blood gas analysis in
      those patients were collected using our innovated clinical research form.
      Statistic methods were applied including descriptive analysis, univariate
      logistic analysis, multivariate correlation logistic analysis, etc. Results:
      (1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100%
      not requiring intubation or non-invasive ventilation), bulbar-muscle weakness
      (121 times, 95.28%), the increased blood partial pressure of carbon dioxide
      (PCO(2)) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep
      disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The
      occurrence of dyspnea in combination with bulbar-muscle weakness (P=0.002) or the
      increased blood PCO(2) (P=0.042) often indicated the tendency of crisis. (2) The
      MG symptoms which were proportion to the occurrence of crisis includes: bulbar
      muscle weakness (P=0.028), fever (P=0.028), malnutrition (P=0.066), complications
      (P=0.071), excess oropharyngeal secretions (P=0.005) and the increased blood
      PCO(2) (P=0.007). The perioperative period of thymectomy would not increase the
      risk of crisis. Conclusions: Dyspnea indicates the occurrence of the Pre-Crisis
      State of MG. In order to significantly reduce the morbidity of myasthenia crisis,
      the bulbar-muscle weakness, the increased blood PCO(2), expectoration weakness,
      sleep disorders, infection & fever and excess oropharyngeal secretions should be
      treated timely.

PMID- 29050156
TI  - [Altered expression and clinical significance of plasma PDGF in patients with
      myasthnia gravis].
AB  - Objective: To evaluate the expression and clinical significance of plasma
      platelet derived growth factor (PDGF) in the patients with myasthenia gravis
      (MG). Methods: Plasma samples from 44 MG patients and 34 healthy people were
      collected from August 2015 to December 2016 from the Second Affiliated Hospital
      of Harbin Medical University. The expression of PDGF was detected by MILLIPLEX
      MAP Reagent kit. Furthermore, we analyzed the associations between PDGF
      expression level and quantitative myasthenia gravis score (QMG). Result: The
      expression of PDGF in plasma was significant lower in MG patients (5.8+/-1.3)
      compared with control group (10.1+/-2.2), and the difference was statistically
      significant (t'=-9.767, P<0.001). Meanwhile it was positively related to QMG
      (r=0.777, P<0.01). However, no significant difference in expression of PDGF in MG
      subgroups was observed. Conclusion: The expression of PDGF decreases in MG
      patients, has positive correlation with MG severity, and is not related to age,
      sex and the pathology of thymus samples.

PMID- 29050157
TI  - [Observation of clinical and electrophysiological features in patients with
      distal myasthenia gravis].
AB  - Objective: To explore the clinical and electrophysiological features and
      prognosis of distal myasthenia gravis (MG). Methods: Data of MG patients in
      Beijing Tiantan Hospital from October 2016 to March 2017 were reviewed, including
      thorough neurological examinations, nerve conduction studies, repetitive nerve
      stimulations (RNS) and needle electromyographies. Distal MG patients were
      included and were analyzed as to their clinical and electrophysiological features
      and response to treatments. Results: Four patients (7.7%) could be classified as
      distal type among 52 definitely diagnosed MG patients. They had initial symptoms
      at age 36 to 64 and developed distal limb muscle weakness in the first month to 6
      years after the onset of this disease. Hand muscles were preferentially involved
      in a non-uniform way. And one patient also had leg weakness on his tibialis
      anterior muscles. RNS showed a more significant decrement at slow rates in distal
      muscles, compared with proximal muscles. The baseline compound muscle action
      potentials (CMAP) of the distal affected muscles presented with slightly
      decreased or fluctuating amplitudes. Their weakness of ocular, bulbar, proximal
      and distal limb muscles improved generally after administration of
      acetylcholinesterase inhibitors or steroids plus acetylcholinesterase inhibitors.
      Electrophysiological reexaminations revealed increased baseline CMAPs, reduced
      decrement on RNS, and relief of myogenic changes on needle electromyography.
      Conclusions: Relatively prominent distal limb muscle weakness can be found in a
      minority of MG patients. Besides profound decrement on slow rate RNS, the
      involved distal muscles may have a characteristic decreased baseline CMAP,
      sometimes with a diurnal fluctuation. Distal MG responds well to regular
      treatments. Its short-term prognosis seems similar to that of common MG with
      proximal predominance.

PMID- 29050158
TI  - [CT perfusion analysis on the association of permeability surface with hematoma
      and edema volume in acute spontaneous putaminal and thalamic hematoma].
AB  - Objective: To discuss the correlation of permeability surface (PS) with hematoma
      and edema volume in acute spontaneous putaminal and thalamic hematoma using CT
      perfusion imaging. Methods: A total of 48 acute spontaneous putaminal and
      thalamic hemorrhage patients were enrolled in this study during October 2015 and
      December 2016 at the First Affiliated Hospital of Wenzhou Medical University. At
      the image slice with maximum size of hematoma, PS was measured by drawing various
      regions of interest (ROI) including"hot spots", perihematomal regions, outward
      regions, hemisphere regions and contralateral mirror regions. The relative PS
      (rPS) was calculated as the ratio of ipsilateral to contralateral PS value in
      each ROI. Hematoma and edema volumes were traced and obtained with commercial
      software. Results: The"hot spots"PS ((2.8+/-1.5) ml.100 g(-1).min(-1)) and
      perihematomal PS ((2.1+/-1.4) ml.100 g(-1).min(-1)) were both significantly
      higher than the PS of the contralateral mirror regions ((1.1+/-0.5) ml.100 g(
      1).min(-1)) (P<0.001). There was no significant difference in outward regions PS
      and contralateral mirror regions PS (P>0.05), nor in hemisphere regions PS and
      contralateral mirror regions PS (P>0.05). There was no significant difference
      in"hot spots"rPS and perihematomal rPS (P=0.218). The"hot spots"rPS and
      Perihematomal rPS were both higher than the rPS of the outward and hemisphere
      regions (P<0.01). There was no significant difference in the outward and
      hemisphere regions (P<0.01). The median hematoma volume was 12.63 ml and the
      median edema volume was 12.36 ml. The edema volume had a positive association
      with the hematoma volume(r=0.799, P<0.001) and perihematomal PS(r=0.465,
      P=0.001). Perihematomal PS had a positive association with the hematoma volume
      (r=0.386, P=0.007). Conclusion: The damage of blood-brain barrier around acute
      spontaneous hematoma can be measured via CT perfusion imaging. Perihematomal PS
      was associated with the hematoma and edema volume.

PMID- 29050159
TI  - [Value of diffusion-weighted imaging in differentiating sellar malignant germ
      cell tumors from raniopharyngioma].
AB  - Objective: To investigate the diagnostic value of diffusion-weighted imaging
      (DWI) and apparent diffusion coefficient(ADC) values in the differentiation of
      sellar malignant germ cell tumors and raniopharyngioma. Methods: This
      retrospective study included 36 patients(14 cases of malignant germ cell tumor
      and 22 patients with raniopharyngioma) with histopathologically-confirmed sellar
      tumors from January 2013 to April 2017 in the First Affiliated Hospital of
      Zhengzhou University.All patients underwent conventional MRI and DWI before the
      treatment. ADC maps were reconstructed, and ADC values of the sellar lesions were
      calculated and compared between the groups. Diagnostic value of ADC was evaluated
      by receiver operating characteristic(ROC) curves. Results: The mean ADC values of
      malignant germ cell tumors were significantly lower than that in
      raniopharyngioma[(0.93+/-0.23)*10(-3) mm(2)/s vs (1.69+/-0.21)*10(-3) mm(2)/s, t=
      10.19, P<0.01]. The area under the ROC curves of ADC values diagnosing malignant
      germ cell tumors and raniopharyngioma was 0.987. The optimal cutoff values of ADC
      for differential diagnosis of malignant germ cell tumors and raniopharyngioma was
      1.52*10(-3) mm(2)/s, the sensitivity, specificity and accuracy was 81.2%, 100%,
      88.9%, respectively. ADC value had a high consistency with pathological results
      (Kappa value was 0.887). Conclusion: Malignant germ cell tumors and
      raniopharyngioma have different ADC value, which can improve the diagnostic
      accuracy.

PMID- 29050160
TI  - [Value of mDIXON-Quant sequence, diffusion-weighted imaging in quantitatively
      diagnosing the sacroiliitis stages].
AB  - Objective: To evaluate the value of mDIXON-Quant sequence, diffusion-weighted
      imaging (DWI) in quantitative diagnosing of the sacroiliitis stages in patients
      with ankylosing spondylitis (AS). Methods: Based on the Bath Ankylosing
      Spondylitis Activity Index (BASDAI) and laboratory parameters, a total of 51
      patients were diagnosed with AS. They were divided into two groups as early
      active group (n=20) and chronic active group (n=31), and at the same time, 25
      healthy people from Tianjin were included as control group. The regular MRI
      sequences and mDIXON-Quant sequence, DWI were obtained. The apparent diffusion
      coefficient (ADC) and fat-signal fraction (FF) value of bone marrow with edema of
      the sacroiliac joints in early active group and chronic active group and of
      subchondral bone marrow of sacroiliac joint in control group all were measured by
      ADC maps and FF maps. Mean (FF, ADC) values were compared between groups.
      Results: The ADC value of the early active group, chronic active group and the
      control group is (1.07+/-0.20)*10(-3)mm(2)/s, (1.00+/-0.22)*10(-3)mm(2)/s,
      (0.25+/-0.07)*10(-3)mm(2)/s, respectively, and the differences of ADC value
      between early active group and control group, chronic active group and control
      group were significant (P<0.01), but the difference of the ADC value between
      early active group and chronic active group was not significant (P=0.394). That
      is to say, the ADC value can't distinguish the early active group and chronic
      active group. The differences of FF value between groups was significant
      (P<0.01), and the FF value of bone marrow with edema in chronic active group were
      higher than that in early active group. Conclusions: The mDIXON-Quant sequence
      can quantitatively diagnose early active group and chronic active group, and the
      diagnostic value is better than DWI. Thus, it can provide guidance for clinical
      treatment and prognosis.

PMID- 29050161
TI  - [Oblique puncture approach via anterolateral to C2: a study of imaging anatomy on
      corpses].
AB  - Objective: To determine the anatomical relation between the carotid artery or
      laryngopharynx and the needle path via anterolateral oblique approach to C2
      vertebral body, and whether the simulated path can direct the actual procedure.
      Methods: Contrast agent was injected into bilateral carotid arteries of 10 fresh
      cadavers (20 sides), and then CT scans were performed on each subject. Bilateral
      simulated puncture paths were simulated on the image of two-dimensional
      reconstruction CT. The distance between the puncture site and middle line(AC),
      the angle between the simulated puncture paths and the median sagittal plane
      (AOB), the distance between the simulated puncture paths and the side wall of
      hypopharynx, or the carotid artery was measured respectively. Under the guidance
      of fluoroscopy, oblique puncture via anterolateral to C2 was performed according
      to the simulated parameters, and then CT was done. The actual needle path was
      measured on the image of two-dimensional reconstruction CT. The outcomes were
      compared by using paired t test between groups. Results: Bilateral simulated
      puncture paths in all 10 cadavers were achieved on the image of CT. The bilateral
      punctures via anterolateral to C2 were successfully performed under fluoroscopic
      guidance in 10 cadavers, and the actual needle path could be showed on the image
      of two-dimensional reconstruction CT. The AC, angle AOB, the distance to carotid
      artery and side wall of laryngopharyngeal of the left simulated path was(4.7+/
      1.0)cm, (33+/-8) degrees , (6.7+/-2.6)mm, (6.6+/-2.8)mm, respectively; and those
      in the right side was(5.2+/-1.3) cm, (36+/-8) degrees , (7.5+/-2.2) mm, (7.2+/
      2.5) mm, respectively.The AC, angle AOB, the distance to carotid artery and side
      wall of laryngopharyngeal of the left actual needle was(4.5+/-1.1) cm, (33+/-9) 
      degrees , (6.7+/-3.0) mm, (7.1+/-3.9) mm, respectively; and those in the right
      side was(5.1+/-1.5) cm, (35+/-10)  degrees , (7.4+/-2.1) mm, (7.2+/-2.6) mm,
      respectively.And the actual and simulation data of both sides were compared and
      no significant differences was found by t test (t=0.104-1.882, all P>0.05).
      Conclusion: The simulated approach via anterolateral to C2 can be achieved on the
      image of two-dimensional reconstruction CT, it is consistent with the real needle
      path and can be used to direct the actual practice to improve the accuracy and
      safety.

PMID- 29050162
TI  - [Two-stage total hip arthroplasty using an antibiotic-loaded cement spacer for
      infected internal fixation of hip fractures].
AB  - Objective: To evaluate the application and clinical results of two-stage total
      hip arthroplasty in the treatment of the deep hip infection following the
      internal fixation of hip fractures. Methods: From May 2007 to November 2014, 21
      patients with active hip infection secondary to internal fixation of hip
      fractures were treated with two-stage total hip arthroplasty using a temporary
      antibiotic-loaded cement spacers. Of 21 cases, 15 were males and 6 were females,
      aged from 27 to 64 years (mean, 45); there are 18 cases of femoral neck fractures
      and 3 cases of intertrochanteric fractures. The serologic examination and X-ray
      were taken at 1 month, 3 months, 6 months, 12 months and annually thereafter post
      operatively to evaluate the clinical results and prosthesis status. Harris hip
      score system was used to evaluate the joint function. Results: All patients were
      successfully treated with two stage operations under general anesthesia. The
      operational interval was 12-44 weeks (mean, 21) and 1 spacer breakage. For the
      arthroplasty, cementless components were used in 20 cases and cemented component
      was use in 1 case. The patients were followed up 25-102 months ( mean, 55 ) and
      infections were eradicated in all hips. The Harris hip score was improved from
      23.24+/-11.81 pre-operatively to 90.24+/-3.92 post-operatively and the difference
      was statistically significant (P<0.05). According to this scoring criteria, the
      excellent and good rate reached up to 95%. At latest fellow-up, the location of
      prosthesis were well and the function of hip joint was satisfied. All cases had
      no dislocation, periprosthetic fracture, ectopic ossification or any other
      complications at the latest fellow-up. Conclusion: By means of an antibiotic
      loaded cement spacer, two-stage total hip arthroplasty is an effective salvage
      procedure eradicating infection and providing functional improvement to the
      infected internal fixation of hip fractures. The early and mid-term clinical
      effects are satisfied.

PMID- 29050163
TI  - [Preliminary outcomes of percutaneously looped thread transection in the surgical
      treatment of stenosing tenosynovitis].
AB  - Objective: To investigate the percutaneously looped thread transection for
      treatment of stenosing tenosynovitis and evaluate its treatment outcome. Methods:
      From January 2014 to October 2016, Eighty-four patients with stenosing
      tenosynovitis were randomly divided into the open decompressionand group (42
      cases) and percutaneously looped thread transection group (42 cases) in
      Department of Orthopedics, Affiliated Laiwu Hospital of Taishan Medical College.
      Incision near the digit horizontal stripes, tendon sheath were cut off in the
      open decompressionand group. Percutaneously looped thread transection was under
      the guidance of ultrasound, threading from the deep and shallow transverse tendon
      sheath, respectively, forming loops to cut off and decompressed the flexor
      tendon. Visual analog scale(VAS) was used to evaluate the extent of pain before
      the operation and 1 or 4 weeks after the operation, the comprehensive curative
      effect were evaluated 3 months after the operation. Results: In the two groups
      pain was alleviated. The VAS improved from (7.0+/-1.3)prior operation to(5.2+/
      1.6) and (2.8+/-1.1)1 week and 4 weeks after the operation in the open
      decompressionand group , respectively. The difference before and after the
      operation was significant(P<0.05). The VAS improved from (7.1+/-1.4) prior
      operation to(2.7+/-1.3) and (0.6+/-0.2)1 week and 4 weeks after the operation in
      the percutaneously looped thread transection group, respectively. The difference
      before and after the operation was significant(P<0.05). The difference of VAS
      scores between two groups at 1 week and 4 weeks after the operation were
      different(P<0.05). The difference of the comprehensive curative effect between
      two groups at 3 months after the operation were not different(P>0.05). There were
      no infection, poor healing, blood vessel and nerve damage after operation in both
      two groups. Conclusion: Percutaneously looped thread transaction under ultrasound
      for the surgical treatment of stenosing tenosynovitis has less trauma and rapid
      recovery. It has such advantage as being effective, simple , and reach the same
      effects as the open decompression surgery.

PMID- 29050164
TI  - [Comparisons of prevalence and clinical and environmental characteristics between
      Tibetan and Han Women with polycystic ovarian syndrome in Tibetan Plateau].
AB  - Objective: By the preliminary comparison study on the constituent ratio and
      clinical characteristics of polycystic ovary syndrome (PCOS) in Tibetan and Han
      women in Tibetan Plateau, we aimed to find the relevance of its pathogenic
      factors, and to guide the treatment of PCOS in the plateau region and improve the
      prognosis. Methods: The general situation and clinical data of 165 patients who
      were diagnosed with PCOS from December 1, 2015 to November 30, 2016 in the
      Department of Obstetrics and Gynecology of the People's Hospital of Tibet
      Autonomous Region were analyzed retrospectively. The prevalence of PCOS among
      Tibetan and Han women in Tibetan Plateau were compared. Results: (1) A total of 1
      520 patients were treated in the Tibet Autonomous Region People's Hospital
      gynecological endocrinology clinics in one year (Tibetan 865 cases, Han 617
      cases, other ethnic groups 38 cases), of which patients with PCOS accounted for
      10.9% (165/1520). (2) The incidence of Tibetan PCOS patients with oligomenorrhea,
      infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI>=24), and
      waist circumference >80 cm were 21.2% (35/165), 20.6% (34/165), 16.4% (27/165),
      28.5% (47/165), 17% (28/165), 38.2% (63/165), 23.6% (39/165), and 36.4% (60/165),
      respectively. The incidence of Han PCOS patients with oligomenorrhea,
      infertility, amenorrhea, acne, hairy, LH/FSH inverted, overweight (BMI>=24), and
      waist circumference >80 cm were 7.9% (13/165), 10.3% (17/165), 9.1% (15/165),
      15.2% (25/165), 9.7% (16/165), 14.5% (24/165), 10.9% (18/165) and 19.4% (32/165),
      respectively. The proportion of high testosterone in Tibetan PCOS patients was
      higher than that in Han PCOS patients with statistically significant. (3) The
      chief complaint of Tibetan PCOS patients were oligomenorrhea and infertility, and
      the chief complaint of Han PCOS patients were infertility and amenorrhea. (4) The
      constituent ratio of outpatient clinics in Nyingchi who were with PCOS at an
      average elevation of about 3 000 meters in the Tibetan Plateau was 7.9% (13/165),
      and the average constituent ratio in Lhasa, Xigatse and Nagqu over 3 500 meters
      above sea level was 35.8% (59/165), 16.9% (28/165) and 15.8% (26/165),
      respectively. Conclusion: The prevalence of PCOS in Tibetan areas is slightly
      higher than that in the international community. The clinical manifestations of
      Tibetan patients with PCOS are significantly different from those of Han patients
      with PCOS. The higher the altitude, the higher the incidence of PCOS.

PMID- 29050165
TI  - [Ovarian tumor associated with anti-N-methyl-D-aspartate receptor encephalitis: a
      report of 15 cases].
AB  - Objective: To summarize the clinical features of patients with ovarian tumor and
      anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis, and to explore the
      influence of operation patterns on the prognosis. Methods: The clinical
      information of patients with ovarian tumor and anti-NMDAR encephalitis in The 3rd
      Affiliated Hospital of Sun Yat-Sen University and The Zhujiang Hospital of
      Southern Medical University were collected and analyzed. Results: There were 15
      patients were enrolled in this study, with the average age of 24.5+/-5.0 years
      old. The most frequent first symptom was psychosis. The main clinical features
      were psychosis, seizures, conscious disturbance, autonomic dysfunction,
      dyskinesia, central hypoventilation and impaired memory. Most patients' symptoms
      were relieved after immunotherapy and surgery. The number of favorable prognosis
      of patients (mRS score 0-2) with ovariectomy was higher than that of the patients
      with ovarian cystectomy (5 vs 3). But the difference had no statistical
      significance (P=0.529). Conclusions: For young female patients with psychosis, we
      should be alert to the possibility of anti-NMDAR encephalitis and screen for
      tumor. Treated with immunotherapy and operation, most patients can get a
      favorable prognosis.

PMID- 29050166
TI  - [Clinic pathological and ultrasonographic features of primary thyroid lymphoma].
AB  - Objective: To analyze the ultrasonographic and clinicopathological features of
      primary thyroid lymphoma(PTL). Methods: The ultrasonographic and
      clinicopathological featuresof 21 cases of pathologically-confirmed PTLs were
      analyzed retrospectively. Results: Of all 21 PTLs, 15 cases were diffuse large B
      cell lymphoma, 4 were mucosal-associated lymphoid tissue extranodular marginal
      zone B-cell lymphoma, 1 was small B-cell lymphoma and 1 was classical Hodgkin
      lymphoma. Eight cases were proved by pathology with concomitant Hashimoto's
      thyroiditis. Ultrasonography observed bilateral or unilateral asymmetric goiter
      (21/21, 100.0%), marked hypoechogenicity (21/21, 100.0%) with posterior acoustic
      enhancement (19/21, 90.5%), heterogeneous echo texture with interspersed linear
      echogenic strands or intensive reticular echogenic strands or cloud echogenic,
      heterogeneous echo texture of thyroid gland (21/21, 100.0%), focal nodular
      hypoechoic(2/21, 9.5%) with regular or irregular shape, increased vascularity
      (13/21, 61.9%) and cervical lymphadenopathy (12/21, 57.1%). Two cases involved
      the anterior cervical muscle and 1 infiltrated trachea. Rapidly enlarging
      cervical mass were found in 13 cases (13/21, 61.9%)with associated compressive
      symptoms such as dyspnea, dysphagia and hoarseness. There was no any indisposed
      symptom in 3 cases. Conclusion: PTL has some common ultrasonographic and clinical
      features, core needle biopsy should be warranted to prove PTL.Surgical resection
      should be considered when needed to reduce misdiagnosis.

PMID- 29050167
TI  - [Serum procalcitonin in patients with pulmonary infection and central nervous
      system injury].
AB  - Objective: To evaluate the influence of serum procalcitonin in the diagnosis and
      treatment of pulmonary infection in patients with central nervous system injury.
      Methods: From October 2014 to February 2017, a retrospective study was performed.
      A total of 1 852 patients were screened in Department of Intensive Care Unite,
      First Affiliated Hospital of Sun Yat-sen University.Among them, 173 patients were
      identified with different kinds of infection. Finally, a total of 42 patients
      with pulmonary infection were enrolled. The clinical data of patients with
      pulmonary infection and central nervous system (CNS) injury was collected. A
      univariate and multivariate regression analysis was performed to study the
      correlation of serum procalcitonin (PCT) with clinical symptoms and signs of the
      pulmonary infection, body temperature(T), white blood cell count (WBC),
      percentage of neutrophils (NEU) and the severity of the pulmonary infection
      (CPIS). The relationship of serum PCT with type of CNS injury, GCS, and exogenous
      glucocorticoid was further studied. Results: During the period of pulmonary
      infection, the peak PCT was 0.83 (0.29, 2.79) MUg/L and the CPIS was 5.50 (5.00,
      7.00). In 9 of 42 patients, the peak PCT was less than 0.25 MUg/L. In 7 of 42
      patients, the peak PCT was ranged from 0.25 to 0.5 MUg/L. In 12 of 42 patients,
      PCT was ranged from 0.5 to 2 MUg/L. Only 10 patients had a PCT 2-10 MUg/L and 4
      patients had a PCT more than 10 MUg/L. There is no correlation between serum PCT
      and body temperature, white blood cell, percentage of neutrophils and CPIS. There
      was no significant differences in patients with PCT<0.5 or >=0.5 MUg/L regarding
      the body temperature, white blood cell, percentage of neutrophils and CPIS.
      However, serum PCT in patients with pulmonary infection had independent
      correlation with the post CNS injury day (beta=0.17, 95% CI (0.02, 0.32),
      P<0.05). The serum PCT was 1.26 (0.47, 2.7) MUg/L and 29.41% patients with a PCT
      less than 0.5 MUg/L within 3 days post CNS injury. Serum PCT level was 0.23
      (0.16, 0.39) MUg/L, and 77.78% patients with a PCT less than 0.5 MUg/L at day 4
      to day 7 post-injury. The PCT level was 0.52 (0.33, 1.12) MUg/L, and 44.44%
      patients with a PCT less than 0.5 MUg/L at day 8 to day 14. The PCT was 3.26
      (2.07, 12.40) MUg/L, and no patient with a PCT less than 0.5 MUg/L after day 15
      post-injury. There were no significant relationship found between serum PCT level
      and type of the disease and surgery, GCS, and use of exogenous glucocorticoid.
      Conclusions: Serum PCT had no significant increase and was not able to be used in
      guiding the antibiotics use in patients with CNS injury and pulmonary infection.

PMID- 29050168
TI  - [Clinical effectiveness of pleural abrasion in video-assisted thoracic surgery
      for bullae resection].
AB  - Objective: To evaluate the efficacy of pleural abrasion in treatment of
      spontaneous pneumothorax with video-assisted thoracic surgery (VATS) for bullae
      resection. Methods: The clinical data of 158 patients with initial spontaneous
      pneumothorax who underwent video-assisted thoracic wedge resections with or
      without pleural abrasion in Henan Provincial People's Hospital from June 2010 to
      June 2015 were retrospectively analyzed. The patients were assigned to two equal
      groups according to whether pleural abrasion was applied or not: experimental
      group (with pleural abrasion) and control group (without pleural abrasion); and
      there were 79 patients in each group.There were 62 males and 17 females aged 15
      60 years (mean age 34 years) in pleural abrasion group. And there were 70 males
      and 9 females aged 18-60 years (mean age 38 years) in non-pleural abrasion
      group.After surgery, all patients were evaluated for postoperative pain, chest
      tube removal time, hospital stay and other complications.Independent samples t
      test was used to compare the data between groups. Results: Surgeries for 158
      patients were performed successfully.No mortality occurred.There was no
      conversion to thoracotomy.Postoperative pain, operation time, intraoperative
      blood loss, chest tube removal time, pleural canals flowand average hospital stay
      in non-pleural abrasion group was significantly lower for 4.4, 19 minutes, 10 ml,
      21 hours, 87 ml and 1.4 days respectively when compared with those in pleural
      abrasion group (t=32.478, 7.140, 11.093, 7.288, 10.246, 8.070, all P<0.05). There
      was no missing case with a follow-up of 30 months.No complications, such as
      pneumothorax, was observed. Conclusions: Postoperative pain, chest tube removal
      time and hospital stay in non-pleural abrasion group are all lower than those in
      pleural abrasion group.And there is no significant difference in the recurrence
      of pneumothorax between the two groups after VATS bullae resection.

PMID- 29050169
TI  - [Consensus of Chinese experts on prostate neoplasms surgical treatment].
AB  - Prostate neoplasms is the second most common male cancer worldwide. In China, the
      incidence of prostate neoplasms has been rising rapidly over the past several
      years. Minimally Invasive Surgery Group of Chinese Anti Cancer Association
      Genitourinary Oncology Committee presents the Chinese experts consensus on
      prostate neoplasms surgical treatment based on the present situation of prostate
      cancer in China and the latest developments in the world.

PMID- 29050170
TI  - [A Chinese experts consensus of neurophysiological evaluating for microvascular
      decompression].
AB  - With the extensive development of microvascular decompression (MVD),
      perioperative neurophysiological monitoring technology is also developping
      rapidly in our country. To promote the standardization of neurophysiological
      monitoring for MVD in China, the experts consensus was published. This consensus
      includes five sections: indications, stimulation and recording methods,
      intraoperative assessment and warning criteria, influencing factors, and clinical
      application recommendations. Furthermore, recommendations for selection of
      electrophysiological monitoring and recording requirements were attached. This
      consensus will be helpful for the physiocian who is conducting or preparing for
      intraoperative monitoring.

PMID- 29050171
TI  - [Use of prostate health index in diagnosing prostate cancer in Chinese men].
AB  - Objective: To investigate the value of prostate health index (PHI) in the
      diagnosis of prostate cancer in patients with total prostate specific antigen
      (tPSA) <20 MUg/L. Methods: Totally 1 135 patients with tPSA<20 MUg/L and prostate
      biopsy indications at Department of Urology, Fudan University Shanghai Cancer
      Center from March 2013 to April 2016 were enrolled in this study. They were
      tested for serum tPSA, free prostate specific antigen and prostate specific
      antigen isoform 2, from which PHI was calculated. Diagnostic efficacy of PHI and
      tPSA were evaluated using receiver operating characteristic (ROC) curve analysis.
      The detection rates of prostate cancer were calculated in different ranges of
      PHI. Subgroup analysis of 716 patients, who were aged 50 or above with tPSA in
      the range of 4 to 10 MUg/L and digital rectal examination negative, was
      performed. Results: In the biopsied objects with tPSA<20 MUg/L, PHI was
      significantly higher in prostate cancer patients than that in non-cancer patients
      (48.4(37.4) vs. 26.5(16.9), U=52 674.00, P=0.000), PHI was also significantly
      higher in high-grade prostate cancer patients than that of low-grade prostate
      cancer patients (44.5(30.8) vs. 56.4(42.5), U=23 314.00, P=0.000). The area under
      the curve (AUC) of PHI for diagnosing prostate cancer was significantly higher
      than that of tPSA (0.771 vs. 0.627, P=0.000). When PHI was in the range of <27,
      27 to <36, 36 to <55 and >=55, the probability of prostate cancer was 9.4%
      (95%CI: 7.0% to 12.2%), 16.3% (95%CI: 12.2% to 20.8%), 31.0% (95%CI: 25.9% to
      37.3%) and 66.4% (95%CI: 58.9% to 74.2%), respectively. Subgroup analysis showed
      that the AUC of PHI in diagnosing prostate cancer was significantly higher than
      that of tPSA (0.764 vs. 0.569, P=0.000). When PHI was in the range of <27, 27 to
      <36, 36 to <55 and >=55, the probability of prostate cancer was 8.1% (95%CI: 5.4%
      to 11.3%), 14.0% (95%CI: 9.1% to 19.9%), 30.8% (95%CI: 23.6% to 38.7%) and 78.8%
      (95%CI: 66.7% to 88.9%), respectively. Conclusion: PHI is superior to tPSA in the
      diagnosis of prostate cancer in Chinese men with tPSA<20 MUg/L.

PMID- 29050172
TI  - [The impact to operation safety of preoperative renal artery embolization for
      management of diameter>=10 cm renal cell carcinoma].
AB  - Objective: To study the impact to operation safety of preoperative renal artery
      embolization for management of >=10 cm renal cell carcinoma. Methods: The
      clinical data of 239 cases with >=10 cm renal cell carcinoma which all had
      underwent operation in Department of Urology, Peking University First Hospital
      from January 2002 to December 2014 were retrospectively analyzed. Fifty-three
      patients underwent preoperative renal artery embolization (therapeutic group) and
      186 patients did not (control group). The effect of embolization on operative
      time, transfusion requirements, hospitalization, ICU stay and perioperative
      complications were analyzed by comparing the two groups using rank sum test and
      chi(2) test or Fisher exact test. Results: Comparing the therapeutic group and
      control group, there was significant difference in tumor location (on the left or
      right). The mean age, sex, mean primary tumor size, and TNM stage were similar in
      both groups. Comparing the therapeutic group and control group, there were more
      open surgeries in therapeutic group (96.2% vs. 82.3%, chi(2)=6.438, P=0.013).
      There were no significant differences in mean operative time (238 (525) minutes
      vs. 208 (583) minutes, Z=-2.182, P=0.062). The mean blood transfusion (700 (1
      900) ml vs. 925 (8 800) ml, Z=-1.064, P=0.006) had significant difference. The
      therapeutic group had a longer mean hospitalization (21 (50) days vs. 15 (79)
      days, Z=-4.322, P=0.000) and higher rate of intensive care unit stay (54.7% vs.
      34.4%, chi(2)=6.103, P=0.027). There was no significant difference in
      perioperative complications between two groups (0 vs.3.2%, P=0.408). Conclusion:
      Preoperative renal artery embolization in >=10 cm renal cell carcinoma patients
      undergoing operation provides benefit in increasing operation safety and reducing
      perioperative death.

PMID- 29050174
TI  - [Effects of modified three-step procedure for anatrophic nephrolithotomy in the
      treatment of complex staghorn renal calculi].
AB  - Objective: To investigate the effects of modified three-step procedure for
      anatrophic nephrolithotomy in the treatment of complex staghorn renal calculi.
      Methods: A total of 22 patients with complex staghorn renal calculi between June
      2013 and June 2016 at Department of Urology in Guangzhou General Hospital of
      Guangzhou Military Command were retrospective analyzed. There were 13 males and 9
      females, ranging from 35 to 62 years old with mean age of 47 years. There were 17
      patients with dull pain, and 5 patients who were found through physical
      examinations. Kidney calculi located in left kidney in 15 patients, right kidney
      in 7 patients. All patients were treated with modified three-step procedure for
      anatrophic nephrolithotomy. The operation time, blood loss, time of
      intraoperative renal ischemia, and postoperative complications were recorded.
      Serum creatinine (Scr), blood urea nitrogen(BUN), beta(2)-microglobulin(beta(2)
      MG), diseased side glomerular filtration rate(GFR) , and renal cortical thickness
      of the diseased kidney in preoperative and postoperative were compared. The
      clinical data were compared by paired sample t test between pre-operation and
      post-operation. Results: The calculi were completely removed in 22 patients, the
      mean operation time was 84 minutes (50 to 126 minutes), the mean time of
      intraoperative renal ischemia was 31 minutes (20 to 56 minutes), the mean blood
      loss was 246 ml (150 to 360 ml). There were no secondary bleeding or urinary
      fistula happened, the perinephric drainage tub was removed in 3 to 7 days
      postoperative, the mean hospitalization time was 7 days.Compared with the
      preoperative, the Scr ((172.7+/-21.3)MUmol/L vs. (146.4+/-22.8)MUmol/L, t=7.197,
      P=0.000), BUN ((9.2+/-1.8)mmol/L vs. (8.0+/-0.5)mmol/L, t=3.798, P=0.001) and
      beta(2)-MG ((203.0+/-32.0)MUg/L vs. (175.6+/-23.8)MUg/L, t=5.009, P=0.000) in
      postoperative decreased, the diseased side GFR increased ((28.6+/-4.0)
      ml/min(31.8+/-3.3) ml/min, t=-3.521, P=0.002). There were no significant
      difference of diseased renal cortical thickness between preoperative and
      postoperative(t=-1.323, P=0.200). There were 12 patients with postoperative pain,
      2 patients with vomiting, 3 patients with fever, and 2 patients with wound
      infection. The follow-up time was 6 months, no residual stones in 22 patients.
      Conclusion: The modified three-step procedure for anatrophic nephrolithotomy has
      high stone free rates with less effects on renal function and fewer
      complications, the method could be widely applied.

PMID- 29050173
TI  - [Effects of percutaneous nephrolithotomy in the treatment of medullary sponge
      kidney with calculi].
AB  - Objective: To evaluate the effects of percutaneous nephrolithotomy (PNL) in the
      treatment of medullary sponge kidney with calculi. Methods: A total of 77
      patients (91 renal units) of medullary sponge kidney with calculi (MSK group) and
      77 patients (77 renal units) with common kidney stone (control group) received
      PNL at Department of Urology in Peking University People's Hospital from
      September 2006 to February 2016 were analyzed retrospectively. The MSK group
      included 33 males and 44 females with a mean age of (42.1+/-13.2) years, the mean
      stone burden was (3.9+/-1.8) cm. The control group included 36 males and 41
      females with a mean age of (45.3+/-13.0) years, the mean stone burden was (3.6+/
      1.5) cm. The numbers of tracts, the time of operation, the drop of hemoglobin,
      the change of creatine, the time of hospitalization, the stone free rate and
      major complications were compared between the two groups. The measurement data
      and numeration data were compared with t test and chi(2) test. Results: There
      were no significant differences in sex, age, preoperative urinary tract
      infection, stone type, and stone burden between the two groups (all P>0.05). The
      proportion of bilateral renal calculus in MSK group was higher (18.2% vs. 0,
      chi(2)=15.400, P=0.000). There were 159 percutaneous channels were established in
      MSK group while 90 percutaneous channels were established in control group.
      Compared with the control group, the operation time ((88.1+/-37.5) minutes vs.
      (68.5+/-30.1) minutes, t=3.543, P=0.000) and hospitalization time ((15.1+/-8.3)
      days vs. (10.1+/-3.6) days, t=4.816, P=0.000) were longer, the creatinine level
      increased ((101.2+/-62.6) MUmol/L vs. (71.3+/-23.6) MUmol/L, t=3.777, P=0.000),
      the rate of stone free decreased (27.5% vs. 83.1%, chi(2)=51.840, P=0.000) and
      the rate of complications increased (29.9% vs. 11.7%, chi(2)=8.114, P=0.004) in
      MSK group. There was no statistically difference in hemoglobin drop ((12.5+/
      13.2) g/L vs. (13.0+/-10.9) g/L, t=-0.260, P=0.795). Conclusions: Using PNL for
      patients of MSK with calculi has a lower stone free rate and a higher
      complications. It is an effective method for patients of MSK with large and
      complex calculi.

PMID- 29050175
TI  - [Effects of retroperitoneal laparoscopic ureterolithotomy and flexible
      ureteroscopic holmium laser lithotripsy for complex upper ureteral calculi].
AB  - Objective: To explore the clinical effects of retroperitoneal laparoscopic
      ureterolithotomy (RPLU) and flexible-ureteroscopic holmium laser lithotripsy (f
      UHLL) for complicated upper ureteral calculi. Methods: A total of 45 cases of
      complicated upper ureteral calculi between March 2014 and January 2016 in
      Department of Urology, Affiliated Jiangyin Hospital of Southeast University
      Medical College were retrospectively analyzed, there were 32 males and 13
      females, ranging from 27 to 45 years with an average age of (34.1+/-9.5) years.
      Of the 45 patients, 28 had ureteral distortion and 17 had concurrent ureteral
      stones in the lower or middle ipsilateral ureter. In those patients, 20 cases
      underwent f-UHLL, and 25 cases received RPLU. The stone size, operation time,
      hospital stay, stone clearance rates and postoperative fever rates between the
      two groups were compared with t test and chi(2)test. Results: The operation was
      successfully performed in all patients, no complications with leakage of urine or
      ureteral perforation occurred, and no significant difference in renal function
      between the two methods were founded in postoperative period. There was no
      significant difference in operation time((78.4+/-8.5) minuetes vs.(73.3+/-11.3)
      minuetes, t=0.61, P=0.67), time of double J tube removed ((33.8+/-3.4)days vs.
      (37.6+/-8.9) d, t=2.37, P=0.08) and ipsilateral renal glomerular filtration rates
      ((41.3+/-7.6)ml/minuetes vs.(40.5+/-7.1) ml/min, t=0.78, P=1.27) between the two
      groups. However, the hospitalization time ((5.9+/-1.7)days vs. (4.2+/-1.6) days,
      t=1.92, P=0.04), postoperative fever rates (4% vs.30%, chi(2)=5.72, P=0.03) and
      calculus clearance rates (100% vs. 75%, chi(2)=7.03, P=0.01) in RPLU were
      significantly higher than f-UHLL. Besides, 5 patients in the f-UHLL group had
      postoperative stone residue and were treated with extracorpore shock wave
      lithotripsy. Conclusions: Both RPLU and f-UHLL are safety and validity for
      complex upper ureteral calculi. RPLU can improve the rate of calculus removal and
      reduce the rate of postoperative fever.

PMID- 29050176
TI  - [Analysis of diagnosis, therapy and prognosis factors of 103 patients with
      pancreatic neuroendocrine tumors].
AB  - Objective: To discuss the clinical pathology characteristics, strategies of
      diagnosis and therapy, and related prognosis factors of pancreatic neuroendocrine
      tumors(pNET). Methods: Clinical data of 103 pNET cases in Department of
      Pancreatic Surgery, Changhai Hospital of Second Military Medical University were
      collected from January 2006 to December 2015. There were 44 males and 59 females,
      aged from 21 to 77 years with mean age of 48 years.Of the 103 patients, there
      were functional type in 21 cases and no functional type in 82 cases. Related
      factors on diagnosis and treatment were summarized. Moreover, univariate survival
      analysis was performed by Kaplan-Meier method, and COX proportional hazards model
      was used for multivariate survival analysis. Results: The detection rates of the
      B-ultrasound, CT, MRI were 60.2%, 84.6% and 91.3%, respectively, and there were
      44 cases located in pancreatic head, 18 cases in pancreatic neck and 41 cases in
      pancreatic body and tail.G1 was the most common pathological grade, and the
      positive rates of Chromogranin A, Syn, neuron-specific enolase and CAM5.2 were
      97.1%, 97.1%, 91.3% and 93.2%, respectively. The results of statistical analysis
      showed that tumor grade(chi(2)=26.077, P<0.05), Ki-67 index(chi(2)=25.427,
      P<0.05), ENETS stage(chi(2)=5.915, P<0.05), AJCC stage(chi(2)=8.411, P<0.05),
      lymph node metastasis(chi(2)=4.770, P<0.05) and distant metastasis(chi(2)=8.411,
      P<0.05) were associated with the prognosis of pNET, and the tumor grade was an
      independent risk factor of the pNET' overall prognositic factors (HR=3.085,
      P<0.01). Conclusions: The pNET can be located in any part of pancreas, and the
      combination of laboratory and various imaging examinations can help make early
      diagnosis. In addition, tumor grade, Ki-67 index, ENETS stage, AJCC stage, lymph
      node metastasis and distant metastasis were closely related to the prognosis of
      pNET, and the higher the tumor grade, the worse the prognosis.

PMID- 29050177
TI  - [Application of three-dimensional visualization in pancreatic tumor: a pilot
      study].
AB  - Objective: To study the value of three-dimensional(3D) visualization in the
      diagnosis and surgical treatment for pancreatic tumor. Methods: From June to
      September 2016, 26 patients with pancreatic tumors in Jinling Hospital, Medical
      School of Nanjing University were involved. The study included 26 patients(8
      females and 18 males) with mean age of (57+/-12)years (ranging from 23 to 77
      years). And there were 20 malignant tumors and 6 benign tumors. All of them were
      examined with abdominal thin slice CT scanning and the CT images were imported
      into 3D visualization system for 3D visualization. The main elements examined by
      3D visualization included tumor shape, size, and location; distribution and
      morphology of the peripancreatic lymph node; the relationships among neoplasms,
      organs and blood vessels. Results: Among the 26 patients, there were 21 cases
      with pancreatic cancer, of which 15 cases successfully underwent standard
      pancreatectomy. All patients were operated underwent accurate assessment. The 3D
      model demonstrated the origination and bifurcations of blood vessels, and the
      relationships among neoplasms, organs and blood vessels efficiently. The 3D
      technique could facilitate to evaluate response of neiadjuvant chemotherapy in
      the pancreatic cancer patients (n=5).3D reconstruction could detect the lymph
      node metastases accurately (n=12) in patients with pancreatic cancer. 3D
      reconstruction were applied to evaluate the the size and range of tumor on 5
      cases. Conclusions: 3D reconstruction allows stereoscopic identification of the
      spatial relationships between physiologic and pathologic structures.The 3D
      technique could facilitate to evaluate distribution and morphology of the
      peripancreatic lymph node, and to evaluate the relationships among neoplasms,
      organs and blood vessels.

PMID- 29050178
TI  - [Detection and clinical significance of circulating tumor cells in patients with
      colorectal carcinoma].
AB  - Objective: To detect circulating tumor cells (CTC) in patients with colorectal
      carcinoma and to evaluate the relationship among CTC, clinic-pathological
      characteristics and prognosis of colorectal carcinoma. Methods: Peripheral blood
      samples were obtained from 109 patients with colorectal carcinoma in Department
      of General Surgery, Beijing Friendship Hospital, Capital Medical University from
      April 2014 to October 2016. There were 60 male and 49 female patients, aging from
      33 to 86 years with a mean age of (65+/-10) years.CTC were detected using density
      gradient centrifugation and immunofluorescence staining. chi(2) test, Fisher
      exact test and rank-sum test were used to analyze the relation between positive
      rate of CTC and clinical characteristic, respectively. The correlation analysis
      of CTC and common tumor markers was detected by chi(2) test and Spearman test.
      The overall survival of patients was analyzed by Kaplan-Meier curve and Cox
      proportional hazard model. Results: CTC were found in 71 of the 109 patients with
      colorectal carcinoma. The presence of CTC was significantly correlated with N
      stage (Z=4.422, P=0.035) and M stage (chi(2)=4.424, P=0.049). However, CTC was
      not significantly correlated with age, sex, tumor location, tumor size,
      differentiation, T stage, Ki-67 and TNM stage (P>0.05). Meanwhile, there was
      significant correlation between CTC and carcino-embryonic antigen (CEA)
      (chi(2)=4.897, P=0.027; r=0.212, P=0.027) indicated by chi(2) test and Spearman
      correlations analysis. The positive rate of CTC was higher than that of CEA
      (chi(2)=15.45, P=0.000). Survival analysis suggested that positive CTC was poor
      for overall survival in colorectal cancer with adjusted HR as 3.023(95%CI: 1.330
      to 6.872, P=0.008). Conclusions: CTC is helpful to early diagnosis tumor
      recurrence and metastasis. Hence, combined multiple tumor markers, including the
      CTC as common indicators of tumor diagnosis, relapse and metastasis could
      effectively improve the accuracy of diagnosis.

PMID- 29050179
TI  - [The comparison of characters between invasive micropapillary carcinoma and
      invasive ductal carcinoma not otherwise specified of the breast].
AB  - Objective: To analyze the differences of clinicopathological characters and
      prognostic factors between invasive micropapillary carcinoma of the breast (IMPC)
      and invasive ductal carcinoma (IDC) not otherwise specified of the breast.
      Methods: Patients who were treated from June 2008 to April 2016 in Breast Center
      of Beijing Hospital were retrospectively analyzed to evaluate the differences
      between IMPC (n=59) and IDC (n=1 080). Follow-up was done every 3 to 6 months
      postoperatively with a deadline of July 31, 2016. The curves of disease free
      survival (DFS) and overall survival (OS) were drawn by Kaplan-Meier method, and
      survival rates were compared by means of the Log-rank test. Potential prognostic
      variables which were identified on univariate analysis were analyzed with Cox's
      proportional hazards regression model for multivariate analysis. Results: More
      lymph nodes were involved in IMPC group (chi(2)=12.168, P=0.007) which led to
      more later stage in this group (chi(2)=8.950, P=0.011). IMPC group displayed a
      significantly increased rate of lymphovascular invasion (LVI) compared to IDC
      group (chi(2)=13.511, P = 0.001). The expression rate of estrogen receptor (ER)
      and progesterone receptor (PR) was higher in IMPC group than that in IDC group
      (89.8% vs. 76.3% and 88.1% vs. 70.7%, respectively, chi(2)=5.786, 8.332, all
      P<0.05). In multivariate analysis performed with the variables found significant
      in univariate analysis, the only variable found significantly affecting DFS of
      IMPC group was the T stage (T1-2 and T3-4, OR=5.217, 95%CI: 1.401 to 19.430,
      P=0.014), while in IDC group, pathological stage (stage I to II and stage III to
      IV, OR=1.870, 95% CI: 1.262 to 2.771, P=0.002), lymph node positive ratio (LNR)
      (OR=2.222, 95%CI: 1.561 to 3.162, P=0.000), PR (OR=1.856, 95%CI: 1.118 to 3.082,
      P=0.017), and age (<50 years old and >=50 years old, OR=0.695, 95%CI: 0.488 to
      0.989, P=0.043) were prognostic factors. There were two variables found
      significantly affecting OS of IMPC group, which were T stage (OR=3.713, 95%CI:
      1.539 to 8.959, P=0.004) and LNR (OR=2.850, 95%CI: 1.033 to 7.862, P=0.043).
      While in IDC group, LNR was the only variable found significantly affecting OS
      (OR=2.129, 95%CI: 1.324 to 3.425, P=0.002). Compared with IDC, the patients with
      IMPC were more likely to have local or regional recurrence (P=0.006). Although
      the median DFS interval was longer in IDC group (chi(2)=9.739, P=0.002), the
      median OS interval was comparable between the two groups (chi(2)=0.787, P=0.375).
      Conclusion: Although IMPC has lymphotropic feature, tendency of LVI and local or
      regional recurrence, it has an OS which is comparable with IDC.

PMID- 29050180
TI  - [Meta analysis of three-dimensional printing patient-specific instrumentation
      versus conventional instrumentation in total knee arthroplasty].
AB  - Objective: To evaluate the effects of three-dimensional printing patient-specific
      instrumentation(PSI) versus conventional instrumentation(CI) in the total knee
      arthroplasty. Methods: According to "patient-specific" , "patient-matched" ,
      "custom" , "Instrumentation" , "Guide Instrumentation" , "cutting blocks" ,
      "total knee arthroplasty" , "total knee replacement" , "TKA" and "TKR" , the
      literature on PubMed, EMbase, Cochrane library, CBM and WanFang were searched.
      According to the inclusion and exclusion criteria, the high quality randomized
      control trial (RCT) studies about three-dimensional (3D) printing patient
      specific instrumentation versus conventional instrumentation in the total knee
      arthroplasty were collected. The post-operative limb mechanical axis outlier, the
      position of the components outlier, post-operative knee function, operative time,
      post-operative blood transfusion and complications were analyzed by RevMan 5.3
      software. Results: A total of 13 high quality RCT studies were included. The
      results of Meta-analysis show that there were no statistical differences in the
      post-operative limb mechanical axis outlier(Z=0.55, P=0.58, 95% CI: 0.78 to
      1.56), femoral coronal component outlier(Z=0.38, P=0.71, 95% CI: 0.69 to 1.72),
      tibia coronal component outlier(Z=1.95, P=0.05, 95% CI: 1.00 to 3.38), femoral
      rotation angle outlier(Z=0.36, P=0.72, 95% CI: 0.49 to 1.64), post-operative knee
      function(Z=1.18, P=0.24, 95% CI: -0.66 to 2.63), post-operative blood
      transfusions(Z=0.74, P=0.46, 95% CI: -0.10 to 0.05) and complications(Z=0.18,
      P=0.86, 95%CI: -0.07 to 0.05) between the PSI group and the CI group. But there
      are statistical differences in the operation time(Z=2.66, P=0.01, 95% CI: -15.97
      to -2.41)and tibia sagittal component outlier (Z=3.69, P=0.00, 95% CI: 1.43 to
      3.18)between the PSI group and the CI group. Conclusions: In the primary total
      knee arthroplasty the PSI is not superior over the CI for the knee without severe
      knee varus or valgus deformity or contracture deformity, without the deformity
      around the knee and without the knee bone loss and obesity. The use of PSI in the
      primary total knee arthroplasty are not recommend.

PMID- 29050181
TI  - [Development status of three-dimensional printing technology in pancreatic
      surgery].
AB  - Three-dimensional printing springed up for the first time in the late 1970s. As
      one of the representative techniques of the world's third industrial revolution,
      three-dimensional printing technology has a rapid development in mechanical
      manufacturing, industrial design, architectural configuration, biomedical
      sciences and so on. This article is a summary of three-dimensional printing
      technology in pancreatic surgery, in order to recognize the developmental level
      and research progress of three-dimensional printing technology, and to give
      advices about the research prospect and development direction in pancreatic
      surgery field.

PMID- 29050182
TI  - [Research progress on Andersson lesion in ankylosing spondylitis].
AB  - Andersson lesion is a destructive vertebral or disco-vertebral lesion that occurs
      in the late stage of the ankylosing spondylitis. According to the etiology, these
      lesions are usually classified into localized lesions and extensive lesions. The
      history of ankylosing spondylitis and characteristic imaging is the key to the
      diagnosis of Andersson lesion. Conservative treatment may be effective for
      localized lesions. However, surgical intervention is often required for the
      failure of conservative treatment and extensive lesions. Currently, the optimal
      procedure for this problem is spinal osteotomy through pseudarthrosis and
      debridement via posterior-only approach.

PMID- 29050183
TI  - [The diagnostic investigations should be efficient for patients with uveitis].
AB  - Uveitis is a common and etiologically complex disease. The diagnosis of uveitis
      is mainly based on clinical findings, and no ancillary test is needed for
      diagnosis of the most common uveitis entities in China. Ancillary tests, however,
      are needed to identify the underlying cause when the clinical presentation points
      to some specific disease entity, and when infectious uveitis or masquerade
      syndrome is suspected. A variety of ophthalmic imaging techniques and laboratory
      tests analyzing blood or intraocular fluid are currently available for
      etiological identification in uveitis as well as for disease follow-up. When
      these tests are considered, the less invasive, expensive and time-consuming ones
      should be chosen. (Chin J Ophthalmol, 2017, 53: 721-723).

PMID- 29050184
TI  - [Choice of treatment for diabetic macular edema].
AB  - Diabetic macular edema (DME), which is the consequence of the failed blood
      retinal barrier, has become a leading cause of blindness in diabetic patients.
      Vascular endothelial growth factors (VEGF) and a series of inflammatory factors
      participate in the pathophysiology of DME. Laser photocoagulation was accepted as
      the first-line therapy before anti-VEGF therapy was proved to be more effective
      by several clinical trials. Anti-VEGF therapy has been regarded as the standard
      treatment, but there are still lots of cases resistant to anti-VEGF therapy.
      Corticosteroid treatment has also been proved effective, especially in refractory
      DME. This demonstrates that inflammation plays a role in DME as well. Here we
      discuss the situation of anti-VEGF and anti-inflammation therapies for DME. (Chin
      J Ophthalmol, 2017, 53: 724-728).

PMID- 29050185
TI  - [Optical coherence tomography angiography of acute Vogt-Koyanagi-Harada disease].
AB  - Objective: To measure vascular density in retinal and choroidal capillary layers
      by optical coherence tomography angiography (OCTA) and to explore their potential
      clinical values in Vogt-Koyanagi-Harada disease (VKH). Methods: This is a cross
      sectional case-control study. Twenty-one acute VKH cases presented to Peking
      Union Medical College Hospital between April 2015 and July 2015 and 49 healthy
      controls were enrolled in this study. OCTA was performed with a split-spectrum
      amplitude-decorrelation angiography-optical coherence tomography (SSADA-OCT)
      system borrowed from Optovue Inc. Vascular densities of the capillary layers were
      analyzed by the built-in software. Bilateral independent sample t-test was used
      to compare retinal and choroidal vascular density of eyes in acute phase VKH with
      healthy controls. Spearman correlation test was used to analyze the correlation
      between the vascular density of retina and choroid in acute phase VKH and LogMAR
      best corrected visual acuity (BCVA). Results: Mean vascular density of
      superficial capillary plexus (SCP), deep capillary plexus (DCP) and
      choriocapillaris (CC) in eyes of the acute VKH group were statistically lower
      than those of healthy control group (51.56%+/-2.88%, 56.51%+/-2.31%, 58.14%+/
      2.10% vs. 53.55%+/-2.51%, 58.14%+/-2.10%, 58.14%+/-2.10%, t=-3.890, 3.910,-6.554,
      all 3 P values were<0.01). In VKH patients, eyes with retinal detachment (RD) had
      statistically lower mean vascular density in the CC layer than those without
      (NRD) (63.46%+/-2.19% vs. 65.85%+/-1.79%, t=3.890, P<0.01), while no
      statistically significant differences were found in vascular densities of SCP and
      DCP layers between RD and NRD eyes. Spearman's correlation test revealed a
      negative correlation between vascular density of the CC layer and logMAR BCVA(r=
      0.437, P<0.01), while no statistically significant associations were found
      between logMAR BCVA and vascular densities of SCP and DCP. Conclusions: OCTA can
      be used for quantitative detection of vascular density of retina and choroidal
      capillary in acute VKH. There is circulatory disturbance in SCP, DCP and CC of
      acute VKH. Vascular density of CC is associated with visual acuity and retinal
      detachment. (Chin J Ophthalmol, 2017, 53: 735-739).

PMID- 29050186
TI  - [Influent factors for treating procedure of cytomegalovirus retinitis after
      allogeneic bone marrow hematopoietic stem cell transplantation].
AB  - Objective: To explore clinical and laboratory factors that influencing treating
      procedure of cytomegalovirus retinitis (CMVR) after allogeneic bone marrow
      hematopoietic stem cell transplantation (HSCT). Methods: This is a retrospective
      case series study. A total of 9 CMVR patients (15 eyes) between January 2016 and
      March 2017 were included in this study. All patients received intravenous or oral
      ganciclovir, together with intravitreous injection of ganciclovir alone or
      combined with foscanet sodium. One day before the first injection, aqueous humor
      samples from the affected eyes were collected, and CMV-DNA and interleukin-8 (IL
      8) level were examined. Blood samples were acquired and CMV-DNA was examined too.
      Best corrected visual acuity, intraocular pressure (Goldmann), slit-lamp and
      fundus examination, ultra-wide fundus photography were performed before the first
      injection and every visit since then. Fifty eyes were divided into stop treating
      group (Group A) and continue-to-treat group (Group B) according to whether local
      treatment could be seized after loading phase. Image-Pro plus 6.0 was exploited
      to determine the area of CMVR in the retina, together with number of quadrants
      involved and whether macular was involved.Then the clinical and laboratory data
      were compared between two groups. ROC curve was used to calculate the cutoff
      values for quantitative factors that showed significant differences between two
      groups. Results: The interval time between HSCT and diagnosis of CMVR, visual
      acuity and CMV-DNA in the blood at baseline, area of CMVR and number of quadrants
      involved and whether macular was involved didn't show any difference between two
      groups. But the intraocular pressure (Z=-2.488, P=0.017), CMV-DNA (Z=-2.239,
      P=0.013) and IL-8 level (Z=-2.475, P=0.012) in aqueous humor at baseline,
      proportion of eyes with active inflammation in anterior (P=0.003) and proportion
      of eyes with ocular hypertension (P=0.021) in group B were significantly higher
      than those in group A. The cutoff values of intraocular pressure, CMV-DNA and IL
      8 level in aqueous humor at baseline were 14.5 mmHg (P=0.013), 2.99*10(5) copy/ml
      (P=0.025) and 447.8 pg/ml (P=0.013), respectively. Conclusion: Higher intraocular
      pressure, CMV-DNA and IL-8 in aqueous humor at baseline, especially combined with
      active inflammation in anterior segment and ocular hypertension suggest longer
      treating period and more times of intravitreous injections. (Chin J Ophthalmol,
      2017, 53: 740-745).

PMID- 29050187
TI  - [Cytokine analysis of aqueous humor in AIDS patients].
AB  - Objective: To explore the Cytokine of aqueous humor in AIDS patients with
      different eye diseases. Methods: A case-control study including 38 patients who
      was diagnosed as acquired immunodeficiency syndrome(AIDS) at Infectious Center
      and Department of Ophthalmology in Beijing You'an Hospital, Capital Medical
      University. And 16 cases of 38 patients were cytomegalovirus retinitis (CMVR), 14
      cases were HIV-related retinal disease, and 8 cases presented as normal. A series
      of tests were performed including vision acuity check, intraocular pressure,
      fundus photography, blood cell count of CD4+ T lymphocyte and the content of
      cytokines in aqueous humor by Luminex 200(TM) liquid chip analyzer. Intraocular
      pressure was analyzed by one-way ANOVA, visual acuity, CD4(+) T lymphocyte count
      and cytokines were analyzed by Kruskal-Wallis test, the differences between the
      two groups were compared by Mann-Whitney U test corrected with Bonferroni.
      Results: Of the 38 AIDS patients [mean age (33.7+/-10.0) year], 37 were males and
      1 was female. The mean visual acuity of 38 patients is logMAR 1.00(0.000, 1.000).
      The difference of visual acuity among three groups was statistically significant
      (chi(2)=9.963, P=0.007). The visual acuity in CMVR group was significantly higher
      than that in HIV-related retinal disease group and AIDS-normal eye group. There
      was no statistically significant difference of intraocular pressure among three
      groups (F=0.830, P<0.05). The mean CD4+ T lymphocyte count was 58(4, 550)/MUl and
      the difference was statistically significant among three groups(chi(2)=6.106,
      P=0.047). The CD4+ T lymphocyte count in AIDS-normal eye group was significantly
      higher than that in CMVR group and HIV-related retinal disease group. There was
      no statistically significant difference in CD4+ T lymphocyte count between HIV
      related retinal disease group and CMVR group. The following cytokines in CMVR
      group were significantly higher than the other two groups with statistically
      significant differences: MIP-1b, IL-6, TNF-alpha, VEGF, IL-8, MCP-1, IP-10.
      Conclusions: In patients who was diagnosed as AIDS, cytomegalovirus retinitis
      would damage vision acuity seriously. The elevated cytokines' level in aqueous
      humor such as MIP-1b, IL-6, TNF-alpha, VEGF, IL-8, MCP-1, IP-10, compared with
      HIV-related retinal disease and AIDS-normal eye cases, may be related to the
      activity of Th1 cell and monocyte-macrophages system including chemokines,
      inflammatory factors, and vascular endothelial factors. (Chin J Ophthalmol, 2017,
      53: 746-752).

PMID- 29050188
TI  - [Sturge-Weber syndrome in port-wine stain patients: a retrospective study on the
      clinical features and screening strategy].
AB  - Objective: To investigate the clinical characteristics of Sturge-Weber syndrome
      (SWS) in the patients with Port-wine stain (PWS). Methods: A total of 279 PWS
      patients, 164 males, 115 females with a median age of first visit 17.00 (4.75,
      56.00) months. Most of the PWS patients were referred to the Ophthalmology
      Department for screening eye problems when the cutaneous angiomas involved the
      ophthalmic division of the trigeminal nerve distribution. The intraocular
      pressure (IOP), cup to disk ratio (C/D), corneal condition and other essential
      measurements were examined to screen glaucoma or choroidal hemangioma. The
      differences of age, gender and vascular ectasia in the ipsilateral eyes were
      compared among PWS and SWS patients with chi-square test. The differences about
      the first visit time, IOP, C/D and corneal diameters were evaluated with
      independent-sample T test or nonparametric test followed by Mann-Whitney U test.
      Results: A total number of 66 out of 279 PWS patients (23.7%) were confirmed as
      SWS with glaucoma. The IOP of the ipsilateral eye with vascular ectasia in PWS
      and SWS was 13.00 mmHg (1 mmHg=0.133 kPa) (IQR: 9.75, 17.00) and 23.00 mmHg
      (20.00, 32.00), respectively (Z=-8.212, P<0.001); the IOP differences between the
      ipsilateral and contralateral eye in PWS and SWS was 1mmHg (0, 2) and 7 mmHg (3,
      11) respectively; the C/D in the ipsilateral eye and the contralateral eye was
      0.30 (0.30, 0.35) and 0.7 (0.6, 0.8) respectively in SWS cases with secondary
      glaucoma. Conclusions: There is a high proportion of SWS with glaucoma in
      ophthalmic division affected PWS patients. Fundus examinations were necessary for
      this type of patients. (Chin J Ophthalmol, 2017, 53:753-757).

PMID- 29050189
TI  - [Clinical features and treatments of retrocorneal fungal infection].
AB  - Objective: To evaluate the clinical features of retrocorneal fungal infection and
      the therapeutic effects. Methods: This was a retrospective, noncomparative study
      of nine patients with retrocorneal fungal infection and an intact corneal
      epithelium treated at Qingdao Eye Hospital. The history, clinical features,
      diagnostic methods, pathogens and therapeutic effects were analyzed. Results:
      Five patients had a history of trauma by plant, two had a non-plant injury, and
      two had unidentified reasons. The duration between the initial onset and the
      first visit to our hospital was 7.9 months (range, 3 months to 2 years). There
      was endothelial plaque and sometimes with white infiltration in the deep stroma,
      but the corneal epithelium remained integrated, and the anterior stroma was
      uninfected. The patients were misdiagnosed as uveitis, herpes simplex keratitis
      or bacterial keratitis in the other hospitals. Visual acuity was 20/200 in four
      eyes, 20/60 in one eye, 20/40 in two eyes, and 20/30 in two eyes. Fungal hyphae
      were detected by confocal microscopy in six eyes. All the eyes had poor response
      to the antifungal medication before penetrating keratoplasty was performed. The
      smear examinations of the corneal endothelial plaque showed fungal hyphae in six
      eyes. Alternaria Nees, Apospory, Phialophora verrucosa, and Fusarium were
      identified. Conclusions: Plant injury is the most common risk factor of
      retrocorneal fungal infection. Slow onset and no initially obvious symptoms may
      lead to delayed diagnosis and misdiagnosis. The diagnosis can be confirmed by
      confocal microscopy before surgery. The effect of antifungal medication is
      usually poor. (Chin J Ophthalmol, 2017, 53:758-765).

PMID- 29050190
TI  - [Current research of sympathetic ophthalmia].
AB  - Sympathetic ophthalmia (SO) is a rare, bilateral, non-necrotizing, granulomatous
      uveitis that usually occurs after open ocular injury or intraocular surgery. The
      pathophysiology is not clearly understood, but generally SO is an immediate
      hypersensitivity mediated by T lymphocytes which are related to ocular tissue
      antigens. The main histopathological features are granulation tissues composed of
      lymphocytes, macrophages and multinucleated giant cells. The clinical
      manifestations are different from person to person, which might be mild or
      severe. Although it could be presented with anterior uveitis, intermediate
      uveitis and posterior uveitis, panuveitis is the most common sign. The ophthalmic
      examinations, such as fundus fluorescein angiography, optical coherence
      tomography and B-scan, could be used to observe the patients' conditions and
      monitor the therapeutic effect. The main treatment of SO is medical therapy with
      corticosteroids, immunomodulators and biomodulators. Topical drug administration,
      including intravitreal injection of triamcinolone acetonide and implantation of a
      fluocinolone acetonide implant, can be considered. There is controversy about
      whether enucleation or evisceration is more appropriate and when the procedure
      should be done. The prognosis of SO could be poor. SO is liable to deteriorate
      and may lead to blindness. This article reviews the etiology, mechanisms,
      histopathology, clinical characteristics, diagnosis and treatment of SO. (Chin J
      Ophthalmol, 2017, 53:778-782).

PMID- 29050191
TI  - [The ocular involvement in the transthyretin-related familial amyloid
      polyneuropathy].
AB  - Transthyretin (TTR)-related familial amyloid polyneuropathy (FAP), which is
      caused by mutant TTR, is a rare but fatal autosomal dominant disease. TTR is
      synthesized by the liver (95%) , the choroid plexus of the brain and the retinal
      pigment epithelium. FAP leads to peripheral neuropathy, and the main ocular
      manifestations are vitreous opacity (yellowish cotton-like), secondary glaucoma
      and keratoconjunctivitis sicca. Liver transplantation has proven to be the most
      effective treatment for TTR-FAP. Nowadays, tafamidis is the only drug approved
      for TTR-FAP (early stage). However, neither liver transplantation nor tafamidis
      is capable to halt the progression of ocular involvement. Panretinal
      photocoagulation could damage the retinal pigment epithelium, and thus prevent
      the progression. Recent investigations on TTR-FAP and its ocular involvement are
      reviewed in this article. (Chin J Ophthalmol, 2017, 53: 783-785).

PMID- 29050192
TI  - [Advances in research of exosomes and age-related macular degeneration].
AB  - Exosomes are small vesicles with a molecular diameter of 30 to 100 nm, which are
      secreted into the cell after the fusion of the multivesicular bodies with the
      plasma membrane. Exosomes contain various molecular constituents of their cell
      origin, including proteins, microRNAs and lipids. Different cell-derived exosomes
      have different biological functions. Exosomes play a very important role in the
      development and progression of age-related macular degeneration (AMD). The
      exosomes derived from the eye are involved in the processes of cell growth,
      metastasis, angiogenesis and immunosuppression by transferring contents to
      adjacent or distant cells. Some of the specific molecules may be used for early
      diagnosis and treatment of AMD. This article reviews the relationship between
      exosomes and AMD pathogenesis and treatment, which may provide a new insight into
      the pathogenesis and treatment strategy of AMD. (Chin J Ophthalmol, 2017, 53:786
      790).

PMID- 29050193
TI  - [The vessel and primary glaucoma].
AB  - Glaucoma, as the first leading cause of irreversible blindness in the world, is a
      chronic progressive optic neuropathy. The pathogenesis of glaucoma is still not
      fully understood till now. A lot of studies about vascular diameter, tortuosity,
      location, disc perfusion, vascular regulation and systemic vascular factors had
      been conducted to investigate the relationship between the vascular states and
      glaucoma since vascular hypothesis proposed. However, direct and convincing
      evidence for primary mechanisms of glaucoma is still lacking. The development of
      OCT, especially the Angio-OCT makes the real time visualization and measurement
      of ocular perfusion in vivo possible, gives some new evidences of vascular
      dysfunction of optic nerve head associated with glaucoma, which enhancing
      thinking of the pathogenesis of glaucoma. This review summarizes the literatures
      on vascular factors associated with glaucoma to provide the references for
      clinical researches. (Chin J Ophthalmol, 2017, 53:791-796).

PMID- 29050195
TI  - Neurobiological insights from bioluminescence imaging.

PMID- 29050194
TI  - Update on the Pathophysiology and Management of Anorectal Disorders.
AB  - Anorectal disorders are common and present with overlapping symptoms. They
      include several disorders with both structural and functional dysfunction(s).
      Because symptoms alone are poor predictors of the underlying pathophysiology, a
      diagnosis should only be made after evaluating symptoms and physiologic and
      structural abnormalities. A detailed history, a thorough physical and digital
      rectal examination and a systematic evaluation with high resolution and/or high
      definition three-dimensional (3D) anorectal manometry, 3D anal ultrasonography,
      magnetic resonance defecography and neurophysiology tests are essential to
      correctly identify these conditions. These physiological and imaging tests play a
      key role in facilitating a precise diagnosis and in providing a better
      understanding of the pathophysiology and functional anatomy. In turn, this leads
      to better and more comprehensive management using medical, behavioral and
      surgical approaches. For example, patients presenting with difficult defecation
      may demonstrate dyssynergic defecation and will benefit from biofeedback therapy
      before considering surgical treatment of coexisting anomalies such as rectoceles
      or intussusception. Similarly, patients with significant rectal prolapse and
      pelvic floor dysfunction or patients with complex enteroceles and pelvic organ
      prolapse may benefit from combined behavioral and surgical approaches, including
      an open, laparoscopic, transabdominal or transanal, and/or robotic-assisted
      surgery. Here, we provide an update on the pathophysiology, diagnosis, and
      management of selected common anorectal disorders.

PMID- 29050196
TI  - Salvage therapy for relapsed testicular cancer.

PMID- 29050197
TI  - Bioresorbable vascular scaffolds: between promises and reality.

PMID- 29050198
TI  - mTORC1/autophagy-regulated MerTK in mutant BRAFV600 melanoma with acquired
      resistance to BRAF inhibition.
AB  - BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors
      (MEKi) were recently approved for therapy of metastatic melanomas harbouring the
      oncogenic BRAFV600 mutation. Although these therapies have shown pronounced
      therapeutic efficacy, the limited durability of the response indicates an
      acquired drug resistance that still remains mechanistically poorly understood at
      the molecular level. We conducted transcriptome gene profiling in BRAFi-treated
      melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically
      upregulated. MerTK overexpression was demonstrated not only in melanomas
      resistant to BRAFi monotherapy (5 out of 10 samples from melanoma patients) but
      also in melanoma resistant to BRAFi+MEKi (1 out of 3), although MEKi alone does
      not affect MerTK. Mechanistically, BRAFi-induced activation of Zeb2 stimulates
      MerTK in BRAFV600 melanoma through mTORC1-triggered activation of autophagy. Co
      targeting MerTK and BRAFV600 significantly reduced tumour burden in xenografted
      mice, which was pheno-copied by co-inhibition of autophagy and mutant BRAFV600.

PMID- 29050199
TI  - Pre-clinical pharmacology of AZD3965, a selective inhibitor of MCT1: DLBCL, NHL
      and Burkitt's lymphoma anti-tumor activity.
AB  - Tumors frequently display a glycolytic phenotype with increased flux through
      glycolysis and concomitant synthesis of lactate. To maintain glycolytic flux and
      prevent intracellular acidification, tumors efflux lactate via lactate
      transporters (MCT1-4). Inhibitors of lactate transport have the potential to
      inhibit glycolysis and tumor growth. We developed a small molecule inhibitor of
      MCT1 (AZD3965) and assessed its activity across a panel of cell lines. We
      explored its antitumor activity as monotherapy and in combination with
      doxorubicin or rituximab. AZD3965 is a potent inhibitor of MCT1 with activity
      against MCT2 but selectivity over MCT3 and MCT4. In vitro, AZD3965 inhibited the
      growth of a range of cell lines especially haematological cells. Inhibition of
      MCT1 by AZD3965 inhibited lactate efflux and resulted in accumulation of
      glycolytic intermediates. In vivo, AZD3965 caused lactate accumulation in the
      Raji Burkitt's lymphoma model and significant tumor growth inhibition. Moreover,
      AZD3965 can be combined with doxorubicin or rituximab, components of the R-CHOP
      standard-of-care in DLBCL and Burkitt's lymphoma. Finally, combining lactate
      transport inhibition by AZD3965 with GLS1 inhibition in vitro, enhanced cell
      growth inhibition and cell death compared to monotherapy treatment. The ability
      to combine AZD3965 with novel, and standard-of-care inhibitors offers novel
      combination opportunities in haematological cancers.

PMID- 29050200
TI  - Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.
AB  - The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2
      proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1
      C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also
      necessary for MM cell survival. The present studies show that targeting MUC1-C
      with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the
      pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1,
      RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1
      transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on
      the BMI1 promoter and thereby activates BMI1 expression. We also show that the
      MUC1-C->MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and
      RING2, we found that MUC1-C drives RING1 by an NF-kappaB p65-dependent mechanism.
      Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was
      associated with downregulation of the PRC1 E3 ligase activity as evidenced by
      decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in
      activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM.
      These findings identify a heretofore unrecognized role for MUC1-C in the
      epigenetic regulation of MM cells.

PMID- 29050201
TI  - HTLV-1 viral oncogene HBZ induces osteolytic bone disease in transgenic mice.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an aggressive T cell malignancy that
      occurs in HTLV-1 infected patients. Most ATL patients develop osteolytic lesions
      and hypercalcemia of malignancy, causing severe skeletal related complications
      and reduced overall survival. The HTLV-1 virus encodes 2 viral oncogenes, Tax and
      HBZ. Tax, a transcriptional activator, is critical to ATL development, and has
      been implicated in pathologic osteolysis. HBZ, HTLV-1 basic leucine zipper
      transcription factor, promotes tumor cell proliferation and disrupts Wnt pathway
      modulators; however, its role in ATL induced osteolytic bone loss is unknown. To
      determine if HBZ is sufficient for the development of bone loss, we established a
      transgenic Granzyme B HBZ (Gzmb-HBZ) mouse model. Lymphoproliferative disease
      including tumors, enlarged spleens and/or abnormal white cell counts developed in
      two-thirds of Gzmb-HBZ mice at 18 months. HBZ positive cells were detected in
      tumors, spleen and bone marrow. Importantly, pathologic bone loss and
      hypercalcemia were present at 18 months. Bone-acting factors were present in
      serum and RANKL, PTHrP and DKK1, key mediators of hypercalcemia and bone loss,
      were upregulated in Gzmb-HBZ T cells. These data demonstrate that Gzmb-HBZ mice
      model ATL bone disease and express factors that are current therapeutic targets
      for metastatic and bone resident tumors.

PMID- 29050202
TI  - Phosphodiesterase 10A is overexpressed in lung tumor cells and inhibitors
      selectively suppress growth by blocking beta-catenin and MAPK signaling.
AB  - Phosphodiesterase 10A (PDE10) is a cyclic nucleotide (e.g. cGMP) degrading enzyme
      highly expressed in the brain striatum where it plays an important role in
      dopaminergic neurotransmission, but has limited expression and no known
      physiological function outside the central nervous system. Here we report that
      PDE10 mRNA and protein levels are strongly elevated in human non-small cell lung
      cancer cells and lung tumors compared with normal human airway epithelial cells
      and lung tissue, respectively. Genetic silencing of PDE10 or inhibition by small
      molecules such as PQ10 was found to selectively inhibit the growth and colony
      formation of lung tumor cells. PQ10 treatment of lung tumor cells rapidly
      increased intracellular cGMP levels and activated cGMP-dependent protein kinase
      (PKG) at concentrations that inhibit lung tumor cell growth. PQ10 also increased
      the phosphorylation of beta-catenin and reduced its levels, which paralleled the
      suppression of cyclin D1 and survivin but preceded the activation of PARP and
      caspase cleavage. PQ10 also suppressed RAS-activated RAF/MAPK signaling within
      the same concentration range and treatment period as required for cGMP elevation
      and PKG activation. These results show that PDE10 is overexpressed during lung
      cancer development and essential for lung tumor cell growth in which inhibitors
      can selectively induce apoptosis by increasing intracellular cGMP levels and
      activating PKG to suppress oncogenic beta-catenin and MAPK signaling.

PMID- 29050203
TI  - Loss of Egr1, a human del5q gene, accelerates BCR-ABL driven chronic myelogenous
      leukemia.
AB  - There is substantial evidence that early growth response-1 (Egr1) gene, a zinc
      finger transcription factor, behaves as a tumor suppressor in leukemia. This
      includes reports from this laboratory that constitutive Egr1 overrides leukemia
      conferred by deregulated c-Myc or E2F-1 in the M1 myeloid leukemic cell line by
      promoting differentiation. To investigate the effect of Egr1 on the initiation
      and progression of Chronic Myelogenous Leukemia (CML), lethally irradiated
      syngeneic wild type mice were reconstituted with bone marrow (BM) from either
      wild type or Egr1 null mice transduced with a 210-kD BCR-ABL-expressing MSCV
      retrovirus (bone marrow transplantation {BMT}). Loss of Egr1 was observed to
      accelerate the development of BCR-ABL driven leukemia in recipient mice,
      resulting in the development of a more aggressive disease, a significantly
      shortened median survival time, and increased BCR-ABL expressing leukemic
      stem/progenitor cells (GFP+Lin-cKit+Sca+). Egr1 deficient progenitors expressing
      BCR-ABL exhibited decreased apoptosis, and increased cell viability and
      proliferation relative to WT counterparts. Secondary BMT of BCR-ABL BM revealed
      that loss of Egr1 resulted in enrichment of LSCs, consistent with shorter
      survival time and more aggressive disease of these mice compared to WT
      counterparts. Furthermore, serial re-plating colony assays indicated that loss of
      Egr1 increased self-renewal ability of BCR-ABL expressing BM. These novel
      findings on the tumor suppressor role of Egr1 in CML provide the impetus to study
      the effect of altering Egr1 expression in AML, where the overall five year
      survival rate remains low. The effect of loss of Egr1 in CML could reflect its
      established functions in normal hematopoiesis, maintaining quiescence of HSCs and
      driving terminal differentiation to the monocyte/macrophage lineage. Gain of
      function studies should validate these conclusions and provide further rationale
      for increased Egr1 as a therapeutic target in AML.

PMID- 29050204
TI  - Irreversible growth plate fusions in children with medulloblastoma treated with a
      targeted hedgehog pathway inhibitor.
AB  - The permanent defects in bone growth observed in preclinical studies of hedgehog
      (Hh) pathway inhibitors were not substantiated in early phase clinical studies of
      vismodegib in children. Consequently, vismodegib advanced into pediatric trials
      for malignancies suspected of being driven by aberrant activation of the Hh
      pathway. In one multicenter phase II trial, vismodegib was added to the therapy
      regimen for newly diagnosed Hh pathway activated medulloblastoma. Herein, we
      report on 3 children (2 on trial and one off trial) treated with vismodegib who
      developed widespread growth plate fusions that persist long after cessation of
      therapy. Currently, all 3 patients exhibit profound short stature and
      disproportionate growth, and 2 subsequently developed precocious puberty.
      Notably, the growth plate fusions only developed after a prolonged exposure to
      the drug (> 140 days). These findings resulted in a major trial amendment to
      restrict the agent to skeletally mature patients as well as a product label
      warning and update. Moreover, these findings alter the risk-benefit ratio of Hh
      inhibitors and underscore the importance of careful study of targeted agents in
      children.

PMID- 29050205
TI  - Catalpol protects synaptic proteins from beta-amyloid induced neuron injury and
      improves cognitive functions in aged rats.
AB  - Synapse loss is one of the common factors contributing to cognitive disorders,
      such as Alzheimer's disease (AD), which is manifested by the impairment of basic
      cognitive functions including memory processing, perception, problem solving, and
      language. The current therapies for patients with cognitive disorders are mainly
      palliative; thus, regimens preventing and/or delaying dementia progression are
      urgently needed. In this study, we evaluated the effects of catalpol, isolated
      from traditional Chinese medicine Rehmannia glutinosa, on synaptic plasticity in
      aged rat models. We found that catalpol markedly improved the cognitive function
      of aged male Sprague-Dawley rats and simultaneously increased the expression of
      synaptic proteins (dynamin 1, PSD-95, and synaptophysin) in the cerebral cortex
      and hippocampus, respectively. In beta-amyloid (Abeta) injured primary rat's
      cortical neuron, catalpol did not increase the viability of neuron but extended
      the length of microtubule-associated protein 2 (MAP-2) positive neurites and
      reversed the suppressive effects on expression of synaptic proteins induced by
      Abeta. Additionally, the effects of catalpol on stimulating the growth of MAP-2
      positive neurites and the expression of synaptic proteins were diminished by a
      PKC inhibitor, bisindolylmaleimide I, suggesting that PKC may be implicated in
      catalpol's function of preventing the neurodegeneration induced by Abeta.
      Altogether, our study indicates that catalpol could be a potential disease
      modifying drug for cognitive disorders such as AD.

PMID- 29050206
TI  - Wnt/beta-catenin signaling promotes aging-associated hair graying in mice.
AB  - Canities is an obvious sign of aging in mouse and human, shown as hair graying.
      Melanocytes in the hair follicle show cyclic activity with hair cycling, which
      transitions from anagen, catagen to telogen. How the hairs turn gray during aging
      is not completely uncovered. Here, by using immunostaining and LacZ staining in
      Dct-LacZ mice, we show that beta-catenin is expressed in melanocytes during hair
      cycling. RT-PCR, western blot and immunostaining show that beta-catenin
      expression is significantly increased in both anagen and telogen skin of aged
      mice, when compared to the anagen and telogen skin of young mice, respectively.
      Overexpression of Wnt10b not only accelerates hair follicle to enter anagen
      phase, but also promotes melanocytes differentiation in young adult mice (2-month
      old), with increased beta-catenin expression in melanocytes at the secondary hair
      germ and matrix region of regenerated hair follicles. Overexpression of Wnt10b
      also promotes melanocyte progenitor cells differentiation in vitro. Our data
      suggest that increased Wnt signaling promotes excessive differentiation of
      melanocytes, leading to exhaustion of melanocyte stem cells and eventually
      canities in aged mice.

PMID- 29050208
TI  - HIF-1alpha:CRAT:miR-144-3p axis dysregulation promotes osteoarthritis chondrocyte
      apoptosis and VLCFA accumulation.
AB  - The functional role(s) of peroxisomes in osteoarthritis remains unclear. We
      demonstrated that peroxisomal dysfunction in osteoarthritis is responsible for
      very-long-chain fatty acid (VLCFA) accumulation. Through gene-profiling analyses,
      we identified CRAT as the gene responsible for this event. CRAT expression was
      suppressed in osteoarthritis chondrocytes, and its knockdown yielded pathological
      osteoarthritic characteristics, including VLCFA accumulation, apoptosis,
      autophagic inhibition, and mitochondrial dysfunction. Subsequent miRNA profiling
      revealed that peroxisomal dysfunction upregulates miR-144-3p, which overlapped
      with the osteoarthritis pathological characteristics observed upon CRAT
      knockdown. Moreover, knocking down HIF-1alpha in normal chondrocytes suppressed
      CRAT expression while stimulating miR-144-3p. Our data indicate that deregulation
      of a HIF-1a:CRAT:miR-144-3p axis impairs peroxisomal function during the
      pathogenesis of osteoarthritis.

PMID- 29050209
TI  - Handgrip strength and subclinical carotid atherosclerosis in relation to platelet
      levels among hypertensive elderly Japanese.
AB  - Age-related disruption of microvascular endothelium exacerbates hypertension and
      sarcopenia; and atherosclerosis is a well-known biological response to vascular
      endothelial injury. Therefore, prevalence of atherosclerosis among hypertensive
      elderly subjects may partly indicate the presence of an appropriate response to
      endothelial injury. We conducted a cross-sectional study of 795 elderly
      hypertensive Japanese subjects aged 60-89 years. Since platelet level is an
      indicator of vascular repair activity, subjects were stratified by platelet
      counts. No significant association between handgrip strength and subclinical
      carotid atherosclerosis (carotid intima-media thickness (CIMT) >=1.1mm) was
      observed for subjects with lower platelet counts, while a significant positive
      association was observed for subjects with higher platelets. Adjusted odds and
      95% confidence intervals of subclinical carotid atherosclerosis for 1 standard
      deviation increments in handgrip strength were 0.86 (0.61, 1.22) for subjects
      with lower platelets and 1.82 (1.26, 2.64) for subjects with higher platelets. A
      positive association between handgrip strength and subclinical carotid
      atherosclerosis exists in hypertensive elderly subjects with higher, but not
      lower, platelet counts. These results lead us to speculate that subjects with a
      beneficial influence on prevention of sarcopenia (maintenance of handgrip
      strength) may possess the capacity of active endothelial repair that causes
      atherosclerosis.

PMID- 29050211
TI  - Silibinin attenuates radiation-induced intestinal fibrosis and reverses
      epithelial-to-mesenchymal transition.
AB  - Radiotherapy is a common treatment for cancer patients, but its use is often
      restricted by the tolerance of normal tissue. As cancer patients live longer,
      delayed radiation effects on normal tissue have become a concern. Radiation
      induced enteropathy, including inflammatory bowel disease and fibrosis, are major
      issues for long-term cancer survivors. To investigate whether silibinin
      attenuates delayed radiation-induced intestinal injury in mice, we focused on
      intestinal fibrotic changes. Silibinin improved delayed radiation injuries in
      mice in association with decreased collagen deposition within the intestines and
      deceased transforming growth factor (TGF)-beta1 levels in the intestine and
      plasma. Treating mice bearing CT26 mouse colon cancer tumors with both silibinin
      and radiation stimulated tumor regression more than radiation alone. We also
      investigated the effect of silibinin on the radiation-induced epithelial-to
      mesenchymal transition (EMT), the primary mechanism of fibrosis. We assessed
      changes in E-cadherin, N-cadherin, and alpha-smooth muscle actin expression, and
      demonstrated that silibinin attenuates radiation-induced EMT. Irradiating
      intestinal epithelial cells increased TGF-beta1 levels, but silibinin suppressed
      TGF-beta1 expression by inhibiting Smad2/3 phosphorylation. These results suggest
      silibinin has the potential to serve as a useful therapeutic agent in patients
      with radiation-induced intestinal fibrosis.

PMID- 29050210
TI  - Astaxanthin acts via LRP-1 to inhibit inflammation and reverse lipopolysaccharide
      induced M1/M2 polarization of microglial cells.
AB  - Microglia become activated during neuroinflammation and produce neurotoxic and
      neurotrophic factors, depending on whether they acquire M1 proinflammatory or M2
      anti-inflammatory phenotypes. Astaxanthin (ATX), a natural carotenoid, has anti
      inflammatory and neuroprotective effects. We investigated whether ATX could
      reverse M1/M2 polarization and suppress neuroinflammation via low-density
      lipoprotein receptor-related protein-1 (LRP-1). We observed increased expression
      of M1 (TNF-alpha, IL-1beta, and CD86) and decreased expression of M2 (Arg-1, IL
      10, and CD206) markers in BV2 microglial cells stimulated with lipopolysaccharide
      (LPS). These alterations were reversed by pretreating the cells with ATX.
      Activation of the NF-kappaB and JNK pathways was observed upon LPS stimulation,
      which was reversed by ATX. ATX-induced M2 polarization was attenuated by
      inhibition of NF-kappaB and JNK. Pretreatment of LPS-stimulated BV2 cells with
      ATX resulted in increased LRP-1 expression. The addition of receptor-associated
      protein, an LRP-1 antagonist, ameliorated ATX-induced inactivation of NF-kappaB
      and JNK signaling, and M2 polarization. ATX promotes M2 polarization to suppress
      neuroinflammation via LRP-1 by inhibiting NF-kappaB and JNK signaling. This novel
      mechanism may suppress neuroinflammation in diseases such as Alzheimer's disease.

PMID- 29050207
TI  - Caloric restriction extends yeast chronological lifespan via a mechanism linking
      cellular aging to cell cycle regulation, maintenance of a quiescent state, entry
      into a non-quiescent state and survival in the non-quiescent state.
AB  - A yeast culture grown in a nutrient-rich medium initially containing 2% glucose
      is not limited in calorie supply. When yeast cells cultured in this medium
      consume glucose, they undergo cell cycle arrest at a checkpoint in late G1 and
      differentiate into quiescent and non-quiescent cell populations. Studies of such
      differentiation have provided insights into mechanisms of yeast chronological
      aging under conditions of excessive calorie intake. Caloric restriction is an
      aging-delaying dietary intervention. Here, we assessed how caloric restriction
      influences the differentiation of chronologically aging yeast cultures into
      quiescent and non-quiescent cells, and how it affects their properties. We found
      that caloric restriction extends yeast chronological lifespan via a mechanism
      linking cellular aging to cell cycle regulation, maintenance of quiescence, entry
      into a non-quiescent state and survival in this state. Our findings suggest that
      caloric restriction delays yeast chronological aging by causing specific changes
      in the following: 1) a checkpoint in G1 for cell cycle arrest and entry into a
      quiescent state; 2) a growth phase in which high-density quiescent cells are
      committed to become low-density quiescent cells; 3) the differentiation of low
      density quiescent cells into low-density non-quiescent cells; and 4) the
      conversion of high-density quiescent cells into high-density non-quiescent cells.

PMID- 29050212
TI  - Recombination activating gene-2null severe combined immunodeficient pigs and mice
      engraft human induced pluripotent stem cells differently.
AB  - This study comparatively investigated the transcriptional, physiological, and
      phenotypic differences of the immune disorder between severe combined
      immunodeficient (SCID) mouse and pig models. We discovered that the recombination
      activating gene-2 (Rag-2) SCID mice, but not RAG-2 SCID pigs, showed intense,
      infrequent, and mild cluster of CD3+-, CD4+-, and CD8+ signals respectively,
      suggesting that distinct species-specific effects exist. Furthermore, the
      expression of six relevant genes (NFATC1, CD79B, CD2, BLNK, FOXO1, and CD40) was
      more downregulated than that in the Rag-2 SCID mice, which provides a partial
      rationale for the death of T/B cells in the lymphoid organs of RAG-2 SCID pigs
      but not in Rag-2 SCID mice. Further, NK cell maturation-related gene expression
      was significantly lower in RAG-2 SCID pigs than in Rag-2 SCID mice. Consistently,
      the RAG-2 SCID pigs, but not Rag-2 SCID mice, developed human induced pluripotent
      stem cell-derived teratomas that were the same as those of perforin/Rag-2 SCID
      mice. Therefore, these unexpected findings indicate the superiority of RAG-2 SCID
      pigs over Rag-2 SCID mice as a suitable model for investigating human diseases.

PMID- 29050213
TI  - Serum protein fingerprinting by PEA immunoassay coupled with a pattern
      recognition algorithms distinguishes MGUS and multiple myeloma.
AB  - Serum protein fingerprints associated with MGUS and MM and their changes in MM
      after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored.
      Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers
      (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr=
      .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major
      histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all
      prosurvival and chemoprotective factors for myeloma cells, were detected in MM
      comparing to MGUS. Comparison of MGUS and healthy subjects revealed elevation of
      angiogenic and antia-poptotic midkine (Pcorr= .0007) and downregulation of
      Transforming growth factor beta 1 (TGFB1, Pcorr= .005) in MGUS. Importantly,
      altered serum pattern was associated with MM-ASCT compared to paired MM at the
      diagnosis as well as to healthy controls, namely by upregulated B-Cell Activating
      Factor (sBAFF) (Pcorr< .006) and sustained elevation of other pro-tumorigenic
      factors. In conclusion, the serum fingerprints of MM and MM-ASCT were
      characteristic by elevated levels of prosurvival and chemoprotective factors for
      myeloma cells.

PMID- 29050214
TI  - Prox1 represses IL-2 gene expression by interacting with NFAT2.
AB  - Interleukin-2 (IL-2) is critical for T lymphocyte activation and regulated by
      many transcriptional factors. Prospero-related homeobox 1 (Prox1) is a
      multifunctional transcription factor, which can work as either a transcriptional
      activator or repressor depending on the cellular and developmental environment.
      We previously reported the Prox1 expression in T cells, raising the possibility
      of Prox1 involvement in the regulation of T cell function and IL-2 production.
      Here we demonstrated that the Prox1 expression in CD4+ T cells was downregulated
      by T cell receptor (TCR) activation. Overexpression of Prox1 attenuated IL-2
      production, while knockdown of endogenous Prox1 by small interfering RNA
      increased IL-2 expression. Mechanistically, we showed that Prox1 inhibited the IL
      2 promoter activity, and associated with the minimal IL-2 promoter. Prox1
      repressed the nuclear factor of activated T cells 2 (NFAT2)-dependent
      transactivation of IL-2 gene by physically binding to NFAT2. The N-terminal
      region of Prox1 was essential for the binding and repression. In summary, our
      findings established Prox1 as a negative regulator in IL-2 gene expression
      through the direct interaction with NFAT2.

PMID- 29050216
TI  - High number of chromosomal copy number aberrations inversely relates to
      t(11;19)(q21;p13) translocation status in mucoepidermoid carcinoma of the
      salivary glands.
AB  - Although rare, mucoepidermoid carcinoma (MEC) is one of the most common malignant
      salivary gland tumors. The presence of the t(11;19)(q21;p13) translocation in a
      subset of MECs has raised interest in genomic aberrations in MEC. In the present
      study we conducted genome-wide copy-number-aberration analysis by micro-array
      comparative-genomic-hybridization on 27 MEC samples. Low/intermediate-grade MECs
      had significantly fewer copy-number-aberrations compared to high-grade MECs (low
      vs high: 3.48 vs 30; p = 0.0025; intermediate vs high: 5.7 vs 34.5; p = 0.036).
      The translocation-negative MECs contained more copy-number-aberrations than
      translocation-positive MECs (average amount of aberrations 15.9 vs 2.41; p
      =0.04). Within all 27 MEC samples, 16p11.2 and several regions on 8q were the
      most frequently gained regions , while 1q23.3 was the most frequently detected
      loss. Low/intermediate-grade MEC samples had copy-number-aberrations in
      chromosomes 1, 12 and 16, while high-grade MECs had a copy-number-aberration in
      8p. The most commonly observed copy-number-aberration was the deletion of 3p14.1,
      which was observed in 4 of the translocation-negative MEC samples. No recurrent
      copy-number-aberrations were found in translocation-positive MEC samples. Based
      on these results, we conclude that MECs may be classified as follows: (i)
      t(11;19)(q21;p13) translocation-positive tumors with no or few chromosomal
      aberrations and (ii) translocation-negative tumors with multiple chromosomal
      aberrations.

PMID- 29050215
TI  - Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic
      intervention.
AB  - Patients with advanced bladder cancer have poor outcomes, indicating a need for
      more efficient therapeutic approaches. This study characterizes proteomic changes
      underlying bladder cancer invasion aiming for the better understanding of disease
      pathophysiology and identification of drug targets. High resolution liquid
      chromatography coupled to tandem mass spectrometry analysis of tissue specimens
      from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive
      bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified
      144 differentially expressed proteins between analyzed groups. These included
      proteins previously associated with bladder cancer and also additional novel such
      as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by
      immunohistochemistry. Pathway and interactome analysis predicted strong
      activation in muscle invasive bladder cancer of pathways associated with protein
      synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation
      initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease)
      in metastatic T24M bladder cancer cells inhibited cell proliferation, migration,
      and colony formation in vitro and decreased tumor growth in xenograft models. By
      contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D)
      recapitulated the effects of EIF3D knockdown in vitro, but not in vivo.
      Collectively, this study represents a comprehensive analysis of NMIBC and MIBC
      providing a resource for future studies. The results highlight EIF3D as a
      potential therapeutic target.

PMID- 29050217
TI  - Triterpenoids from Aglaia abbreviata exert cytotoxicity and multidrug resistant
      reversal effect in MCF-7/ADM cells via reactive oxygen species induction and P
      glycoprotein inhibition.
AB  - Triterpenoids from the Aglaia have been shown cytotoxicity on a broad spectrum of
      human tumor cells. In the present study, we extracted triterpenoids AA-5 (1) and
      AA-6 (2) from stems of Aglaia abbreviata, and studied their cytotoxicity in
      multidrug resistant (MDR) MCF-7/ADM cells. After 48 h treatment, AA-5 (1) and AA
      6 (2) significantly increased mitochondrial-mediated apoptosis by enhancing
      reactive oxygen species (ROS) with depressed mitochondrial membrane potential and
      caspase-9 activities. The drug efflux transporter P-glycoprotein (P-gp) and the
      intracellular antioxidant systems, involving Glutathione S-Transferase pi,
      Glutathione and heme oxygenase-1, were also inhibited via the ROS-depressed
      Akt/NF-E2-related factor 2 pathway. Furthermore, 2 h-treatment of AA-6 (2) at non
      toxic concentrations exhibited MDR reversal effects with no alteration on P-gp
      expression but increased drug accumulation ability. AA-6 alos demonstrated
      synergetic effects with classic anti-tumor agents. Moreover, computational
      modeling studies showed that AA-6 (2) might bind to the modulator site on P-gp
      and act as an inhibitor, not a substrate of P-gp. Therefore, AA-5 (1) and AA-6
      (2) may be effective anti-tumor and reversal agents for the further development
      of therapeutics against MDR breast cancer.

PMID- 29050218
TI  - BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition
      in melanoma.
AB  - The expression of CD47 on the cancer cell surface transmits "don't eat me"
      signalling that not only inhibits phagocytosis of cancer cells by phagocytes but
      also impairs anti-cancer T cell responses. Here we report that oncogenic
      activation of ERK plays an important role in transcriptional activation of CD47
      through nuclear respiratory factor 1 (NRF-1) in melanoma cells. Treatment with
      BRAF/MEK inhibitors upregulated CD47 in cultured melanoma cells and fresh
      melanoma isolates. Similarly, melanoma cells selected for resistance to the BRAF
      inhibitor vemurafenib expressed higher levels of CD47. The increase in CD47
      expression was mediated by ERK signalling, as it was associated with rebound
      activation of ERK and co-knockdown of ERK1/2 by siRNA diminished upregulation of
      CD47 in melanoma cells after exposure to BRAF/MEK inhibitors. Furthermore, ERK1/2
      knockdown also reduced the constitutive expression of CD47 in melanoma cells. We
      identified a DNA fragment that was enriched with the consensus binding sites for
      NRF-1 and was transcriptionally responsive to BRAF/MEK inhibitor treatment.
      Knockdown of NRF-1 inhibited the increase in CD47, indicating that NRF-1 has a
      critical role in transcriptional activation of CD47 by ERK signalling. Functional
      studies showed that melanoma cells resistant to vemurafenib were more susceptible
      to macrophage phagocytosis when CD47 was blocked. So these results suggest that
      NRF-1-mediated regulation of CD47 expression is a novel mechanism by which ERK
      signalling promotes the pathogenesis of melanoma, and that the combination of
      CD47 blockade and BRAF/MEK inhibitors may be a useful approach for improving
      their therapeutic efficacy.

PMID- 29050219
TI  - Preclinical characterization of abemaciclib in hormone receptor positive breast
      cancer.
AB  - Abemaciclib is an ATP-competitive, reversible kinase inhibitor selective for CDK4
      and CDK6 that has shown antitumor activity as a single agent in hormone receptor
      positive (HR+) metastatic breast cancer in clinical trials. Here, we examined the
      mechanistic effects of abemaciclib treatment using in vitro and in vivo breast
      cancer models. Treatment of estrogen receptor positive (ER+) breast cancer cells
      with abemaciclib alone led to a decrease in phosphorylation of Rb, arrest at G1,
      and a decrease in cell proliferation. Moreover, abemaciclib exposure led to
      durable inhibition of pRb, TopoIIalpha expression and DNA synthesis, which were
      maintained after drug removal. Treatment of ER+ breast cancer cells also led to a
      senescence response as indicated by accumulation of beta-galactosidase, formation
      of senescence-associated heterochromatin foci, and a decrease in FOXM1 positive
      cells. Continuous exposure to abemaciclib altered breast cancer cell metabolism
      and induced apoptosis. In a xenograft model of ER+ breast cancer, abemaciclib
      monotherapy caused regression of tumor growth. Overall these data indicate that
      abemaciclib is a CDK4 and CDK6 inhibitor that, as a single agent, blocks breast
      cancer cell progression, and upon longer treatment can lead to sustained
      antitumor effects through the induction of senescence, apoptosis, and alteration
      of cellular metabolism.

PMID- 29050220
TI  - Characterization of a novel androgen receptor (AR) coregulator RIPK1 and related
      chemicals that suppress AR-mediated prostate cancer growth via peptide and
      chemical screening.
AB  - Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding
      domain as bait, we observed enrichment of FxxFY motif-containing peptides.
      Protein database searches revealed the presence of receptor-interacting protein
      kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and
      suppressed AR transactivation in a dose-dependent manner. Domain mapping
      experiments showed that the FxxFY motif in RIPK1 is critical for interactions
      with AR and the death domain of RIPK1 plays a crucial role in its inhibitory
      effect on transactivation. In terms of tissue expression, RIPK1 levels were
      markedly higher in benign prostate hyperplasia and non-cancerous tissue regions
      relative to the tumor area. With the aid of computer modeling for screening of
      chemicals targeting activation function 2 (AF-2) of AR, we identified oxadiazole
      derivatives as good candidates and subsequently generated a small library of
      these compounds. A number of candidates could effectively suppress AR
      transactivation and AR-related functions in vitro and in vivo with tolerable
      toxicity via inhibiting AR-peptide, AR-coregulator and AR N-C interactions.
      Combination of these chemicals with antiandrogen had an additive suppressive
      effect on AR transcriptional activity. Our collective findings may pave the way
      in creating new strategies for the development and design of anti-AR drugs.

PMID- 29050221
TI  - PDGFRA, HSD17B4 and HMGB2 are potential therapeutic targets in polycystic ovarian
      syndrome and breast cancer.
AB  - To explore the key genes associated with both PCOS and breast cancer, we
      overlapped the synchronously differently expressed genes in two obese insulin
      resistant GEO datasets in muscle tissue and genes exert essential roles in breast
      cancer prognosis together base on the following reasons: (1) Androgens excess is
      believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is
      usually complicated with metabolic symptoms, such as obesity and insulin
      resistance. (3) Muscle is the main place where energy metabolism and material
      metabolism take place. Consequently, 53 genes were found, functionally enriched
      in pathways such as pyruvate metabolism, muscle system process and development of
      primary male sexual characteristics etc. We further lay our eyes on genes
      correlated with male sexual characteristics, which may be involved in the onset
      of both PCOS and breast cancer. Three genes were indicated to be associated with
      this process, including hydroxysteroid (17-beta) dehydrogenase 4/HSD17B4,
      platelet-derived growth factor receptor, alpha polypeptide/PDGFRA and high
      mobility group box 2/HMGB2. Gene-drug interaction network about the three genes
      were then constructed. Drugs or chemicals that contribute to correcting the
      disorder of lipid metabolism were detected to restore the abnormal expression of
      the three genes in PCOS, such as simvastatin, bezafibrate, fenofibrate et al,
      which provide further choices for managing patients with PCOS.

PMID- 29050222
TI  - Beneficial effect of fluoxetine treatment aganist psychological stress is
      mediated by increasing BDNF expression in selected brain areas.
AB  - SSRI antidepressant fluoxetine is widely used to treat psychological stress
      related disorders, however the underlying working mechanisms is not fully
      understood, as SSRIs can rapidly increase the extracellular serotonin levels but
      it normally takes weeks to reveal their therapeutic effect in the stress-related
      psychological disorders. Our previous study demonstrated that purely
      psychological stress without any physic stimuli induces a biphasic change in the
      expression of brain-derived neurotrophic factor (BDNF), which immediately
      decrease and then gradually increase after the stress; and that the latter BDNF
      increase in response to the psychological stress involves the activation of
      serotonin system. To investigate the role of BDNF in the fluoxetine treatment for
      stress-related psychological disorders, we examined the mRNA and protein levels
      of BDNF in the brain of Sprague-Dawley (SD) rats, which were pretreated with
      fluoxetine at 10 mg/kg or vehicle solution for 14 days, over 24 hour after an
      acute psychological stress exposure. In situ hybridization and
      immunohistochemistry were performed to detect the expression of BDNF at different
      time points in various brain regions after the psychological stress. We found
      that fluoxetine treatment completely blocked the BDNF decrease induced by the
      psychological stress, and also enhanced the gradual increase in the expression of
      BDNF in most of the brain regions except VTA after the psychological stress. The
      results suggest that the enhancement in BDNF levels induced by chronic fluoxetine
      treatment mediates the therapeutic effect against psychological stress.

PMID- 29050223
TI  - MiR-23a promotes TGF-beta1-induced EMT and tumor metastasis in breast cancer
      cells by directly targeting CDH1 and activating Wnt/beta-catenin signaling.
AB  - TGF-beta1-induced epithelial-mesenchymal transition (EMT) has been proved to be
      associated with metastasis of breast cancer cells. We attempted to detect a novel
      mechanism that microRNAs mediated the TGF-beta1-induced EMT in the process of
      breast cancer metastasis. Here we reported that the expression of miR-23a was
      higher in breast cancer cells with high metastasis ability and patients with
      lymph node metastasis and the treatment of TGF-beta1 significantly upregulated
      the expression of miR-23a in breast cancer cells. We found that miR-23a was
      upregulated by TGF-beta1 post-transcriptionally and Smads directly bound the RNA
      Smad binding element (R-SBE) of miR-23a. Functional studies showed that
      inhibition of miR-23a suppressed the TGF-beta1-induced EMT, migration, invasion
      and metastasis of breast cancer both in vitro and in vivo. In addition, we
      determined that miR-23a directly targeted and suppressed CDH1, one important gene
      in EMT phenomenon. Notably, Wnt/beta-catenin signaling was activated by the
      suppression of CDH1 in the miR-23a mediated process of TGF-beta1-induced EMT and
      tumor invasion. These results demonstrate that miR-23a promotes TGF-beta1-induced
      tumor metastasis in breast cancer by targeting CDH1 and activating Wnt/beta
      catenin signaling. Taken together, our results indicate a novel regulatory
      mechanism of TGF-beta1-induced EMT and suggest that miR-23a might be a potential
      target in breast cancer therapy.

PMID- 29050224
TI  - Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma.
AB  - The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC).
      It accounts for 70-80% of all renal malignancies representing the third most
      common urological cancer after prostate and bladder cancer. The identification of
      non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC
      may represent a relevant step-forward in ccRCC management. The aim of this study
      is to evaluate whether specific miRNAs deregulated in ccRCC tissues present
      altered levels also in urine specimens. To this end we first assessed that miR-21
      5p, miR-210-3p and miR-221-3p resulted upregulated in ccRCC fresh frozen tissues
      compared to matched normal counterparts. Next, we evidenced that miR-210-3p
      resulted significantly up-regulated in 38 urine specimens collected from two
      independent cohorts of ccRCC patients at the time of surgery compared to healthy
      donors samples. Of note, miR-210-3p levels resulted significantly reduced in
      follow-up samples. These results point to miR-210-3p as a potential non-invasive
      biomarker useful not only for diagnosis but also for the assessment of complete
      resection or response to treatment in ccRCC management.

PMID- 29050225
TI  - HCaRG/COMMD5 inhibits ErbB receptor-driven renal cell carcinoma.
AB  - Hypertension-related, calcium-regulated gene (HCaRG/COMMD5) is highly expressed
      in renal proximal tubules, where it contributes to the control of cell
      proliferation and differentiation. HCaRG accelerates tubular repair by
      facilitating re-differentiation of injured proximal tubular epithelial cells,
      thus improving mouse survival after acute kidney injury. Sustained hyper
      proliferation and de-differentiation are important hallmarks of tumor
      progression. Here, we demonstrate that cancer cells overexpressing HCaRG maintain
      a more differentiated phenotype, while several of them undergo autophagic cell
      death. Its overexpression in mouse renal cell carcinomas led to smaller tumor
      size with less tumor vascularization in a homograft tumor model. Mechanistically,
      HCaRG promotes de-phosphorylation of the proto-oncogene erythroblastosis oncogene
      B (ErbB)2/HER2 and epigenetic gene silencing of epidermal growth factor receptor
      and ErbB3 via promoter methylation. Extracellular signal-regulated kinase, AKT
      and mammalian target of rapamycin which mediate ErbB-dowstream signaling pathways
      are inactivated by HCaRG expression. In addition, HCaRG is underexpressed in
      human renal cell carcinomas and more expressed in normal tissue adjacent to renal
      cell carcinomas of patients with favorable prognosis. Taken together, our data
      suggest a role for HCaRG in the inhibition of tumor progression as a natural
      inhibitor of the ErbB signals in cancer and as a potential prognostic marker for
      renal cell carcinomas.

PMID- 29050226
TI  - Cross-talk mechanism between endothelial cells and hepatocellular carcinoma cells
      via growth factors and integrin pathway promotes tumor angiogenesis and cell
      migration.
AB  - Tumor angiogenesis plays a central role in the development and metastasis of
      hepatocellular carcinoma. Cancer cells secrete angiogenic factors to recruit
      vascular endothelial cells and sustain tumor vascular networks, which facilitate
      the migration and invasion of cancer cells. Therefore, the cross-talk between
      vascular endothelial cells and cancer cells is vitally necessary, however, little
      is known about the cross-talk mechanism of these cells interaction. In the
      present study, the proliferation, migration, invasion and tube formation of
      vascular endothelial EA.hy926 cells and hepatocellular carcinoma HepG2 cells were
      studied by exchanging their culture medium. The time-dependent differences of
      integrins induced signaling pathway associated with cell migration were
      investigated. Our results showed that HepG2 cells markedly enhanced the
      proliferation and migration ability as well as the tube formation of EA.hy926
      cells by releasing growth factors. Also, the EA.hy926 cells promoted the
      proliferation, migration and invasion ability of HepG2 cells. The further
      analysis demonstrated that the integrins-FAK-Rho GTPases signaling events in both
      of two cells was activated under conditioned medium, and the signaling molecules
      in two cell lines showed a different time-dependent expression within 1h. These
      findings reveal the cross-talk mechanism between the endothelial cells and
      hepatocellular carcinoma cells, which were expected to find out new ideas for the
      prevention and treatment of hepatocellular carcinoma.

PMID- 29050227
TI  - Identification of two novel biomarkers of rectal carcinoma progression and
      prognosis via co-expression network analysis.
AB  - mRNA expression profiles provide important insights on a diversity of biological
      processes involved in rectal carcinoma (RC). Our aim was to comprehensively map
      complex interactions between the mRNA expression patterns and the clinical traits
      of RC. We employed the integrated analysis of five microarray datasets and The
      Cancer Genome Atlas rectal adenocarcinoma database to identify 2118 consensual
      differentially expressed genes (DEGs) in RC and adjacent normal tissue samples,
      and then applied weighted gene co-expression network analysis to parse DEGs and
      eight clinical traits in 66 eligible RC samples. A total of 16 co-expressed gene
      modules were identified. The green-yellow and salmon modules were most
      appropriate to the pathological stage (R = 0.36) and the overall survival (HR
      =13.534, P = 0.014), respectively. A diagnostic model of the five pathological
      stage hub genes (SCG3, SYP, CDK5R2, AP3B2, and RUNDC3A) provided a powerful
      classification accuracy between localized RC and non-localized RC. We also found
      increased Secretogranin III (SCG3) expression with higher pathological stage and
      poorer prognosis in the test and validation set. The increased Homer scaffolding
      protein 2 (HOMER2) expression with the favorable survival prediction efficiency
      significantly correlated with the markedly reduced overall survival of RC
      patients and the higher pathological stage during the test and validation set.
      Our findings indicate that the SCG3 and HOMER2 mRNA levels should be further
      evaluated as predictors of pathological stage and survival in patients with RC.

PMID- 29050228
TI  - Mutation landscape and intra-tumor heterogeneity of two MANECs of the esophagus
      revealed by multi-region sequencing.
AB  - Mixed adenoneuroendocrine carcinoma (MANEC) in the esophagus is an infrequent but
      highly malignant cancer with few known genomic alterations. We conducted whole
      exome sequencing and whole-genome SNP genotyping for 4-6 tumor subregions and 5-6
      adjacent normal tissue sites and 1-3 lymph node metastases in two esophageal
      MANECs to detect somatic mutations and copy number alterations, and to explore
      their spatial heterogeneity and underlying clonal structure. TP53 mutation, RB1
      deletion or LOH, and PIK3CA, PTEN, KRAS, SOX2, DVL3, TP63 amplification appeared
      in all regions in both tumors. Mutations falling in known cancer genes tended to
      show higher variant allele frequencies than those not falling in these genes in
      at least one of the cases. Phylogenetic analyses of the samples and underlying
      subclones suggested extensive migration across different tumor regions and from
      some regions to the lymph nodes. Lymph node metastases appeared to have been
      seeded by both early founder cells as well as subsequent, locally emerging
      daughter clones. A phenotypically normal tissue site carried most of the
      mutations found in neighboring tumor samples, implying field cancerization.
      Understanding such complex genetic heterogeneity within each patient will be
      important for guiding clinical decisions.

PMID- 29050229
TI  - ESE-1/ELF3 mRNA expression associates with poor survival outcomes in HER2+ breast
      cancer patients and is critical for tumorigenesis in HER2+ breast cancer cells.
AB  - ESE-1/Elf3 and HER2 appear to establish a positive feedback regulatory loop, but
      the precise role of ESE-1 in HER2+ breast tumorigenesis remains unknown.
      Analyzing public repositories, we found that luminal B and HER2 subtype patients
      with high ESE-1 mRNA levels displayed worse relapse free survival. We stably
      knocked down ESE-1 in HER2+ luminal B BT474 cells and HER2 subtype SKBR3 cells,
      which resulted in decreased cell proliferation, colony formation, and anchorage
      independent growth in vitro. Stable ESE-1 knockdown inhibited HER2-dependent
      signaling in BT474 cells and inhibited mTOR activation in SKBR3 cells, but
      reduced Akt signaling in both cell types. Expression of a constitutively-active
      Myr-Akt partially rescued the anti-proliferative effect of ESE-1 knockdown in
      both cell lines. Furthermore, ESE-1 knockdown inhibited cyclin D1, resulting in a
      G1 delay in both cell lines. Finally, ESE-1 knockdown completely inhibited BT474
      cell xenograft tumors in NOD/SCID female mice, which correlated with reduced in
      vitro tumorsphere formation. Taken together, these results reveal the ESE-1
      controls transformation via distinct upstream signaling mechanisms in SKBR3 and
      BT474 cells, which ultimately impinge on Akt and cyclin D1 in both cell types to
      regulate cell proliferation. Particularly significant is that ESE-1 controls
      tumorigenesis and is associated with worse clinical outcomes in HER2 breast
      cancer.

PMID- 29050230
TI  - A potential panel of two-long non-coding RNA signature to predict recurrence of
      patients with laryngeal cancer.
AB  - Accumulating evidence has shown that aberrant lncRNA expression plays an
      oncogenic or tumor-suppressive role in the tumorigenesis of laryngeal cancer.
      However, the prognostic roles of lncRNAs in laryngeal cancer recurrence are still
      poorly understood. In this study, we obtained lncRNA expression profiles of 109
      patients with laryngeal cancer by mining previously published gene expression
      microarray data from the Gene Expression Omnibus (GEO) and identified two lncRNAs
      associated with laryngeal cancer recurrence in the training dataset by using Cox
      regression analysis. Then these two lncRNAs were combined to a two-lncRNA
      signature for identifying patients at high-risk of disease recurrence. By
      applying this two-lncRNA signature to the testing dataset, a clear separation was
      observed in the survival curves between patients with low- or high-risk scores,
      indicating good reproducibility of this two-lncRNA signature in predicting
      disease-free survival of laryngeal cancer. Further analysis revealed that the
      prognostic value of the two-lncRNA signature was independent of other clinical
      features, including age, stage and grade. Subsequent gene set enrichment analysis
      suggested that the two-lncRNA signature was more likely to involve with GPCRs
      downstream signaling pathway, potassium channel pathway and aurora-A pathway. Our
      study demonstrated that the two-lncRNA signature may be a novel potential
      biomarker for prognosis of laryngeal cancer and may provide novel insights into
      the molecular mechanism of laryngeal cancer.

PMID- 29050231
TI  - A phase I study of foretinib plus erlotinib in patients with previously treated
      advanced non-small cell lung cancer: Canadian cancer trials group IND.196.
AB  - PURPOSE: MET and AXL mediate resistance to EGFR TKI in NSCLC. Foretinib, a
      MET/RON/AXL/TIE-2/VEGFR kinase inhibitor may overcome EGFR kinase resistance.
      This dose escalation study combined foretinib and erlotinib in advanced
      pretreated NSCLC patients. EXPERIMENTAL DESIGN: The primary endpoint was to
      define the RP2D of foretinib plus erlotinib as continuous oral daily dosing.
      Secondary objectives included safety, pharmacokinetics, response and potential
      biomarkers of response including EGFR, KRAS genotype, MET, AXL expression, and
      circulating HGF levels. Erlotinib (E100-150 mg) was commenced on day 1 cycle 1;
      if well tolerated, foretinib (F30-45 mg) was added on day 15 cycle 1, using
      standard 3+3 dose escalation. RESULTS: Of 31 patients enrolled in 3 dose levels,
      6 were inevaluable for DLT and replaced. DLT occurred in 3/15 patients at DL2
      (E150 mg, F30 mg): Gr3 pain, mucositis, fatigue and rash. Cycle 1 DLT was not
      seen at DL3 (E150 mg, F45 mg) but 27% experienced dose reduction/interruption.
      Adverse events in >=20% included diarrhea, fatigue, anorexia, dry skin, rash and
      hypertension. No PK interaction was seen with the combination. RP2D was defined
      as erlotinib 150 mg daily x 14 days with foretinib 30 mg added on day 15
      (continuous dosing in 28-day cycles). Responses were seen in 17.8% of response
      evaluable patients (5/28). In 18 samples, baseline MET expression uncontrolled
      for EGFR genotype appeared associated with response. AXL expression was
      associated with neither EGFR mutation nor response. CONCLUSION: Combining
      foretinib and erlotinib demonstrated response in unselected advanced NSCLC but
      also incremental toxicity. Future development will require molecular patient
      selection.

PMID- 29050232
TI  - Progressive modulation of the human olfactory bulb transcriptome during
      Alzheimer's disease evolution: novel insights into the olfactory signaling across
      proteinopathies.
AB  - Alzheimer's disease (AD) is characterized by progressive dementia, initially
      presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first
      central structure of the olfactory pathway, we lack a complete molecular
      characterization of the transcriptional events that occurs in this olfactory area
      during AD progression. To address this gap in knowledge, we have assessed the
      genome-wide expression in postmortem OBs from subjects with varying degree of AD
      pathology. A stage-dependent deregulation of specific pathways was observed,
      revealing transmembrane transport, and neuroinflammation as part of the
      functional modules that are disrupted across AD grading. Potential drivers of
      neurodegeneration predicted by network-driven transcriptomics were monitored
      across different types of dementia, including progressive supranuclear palsy
      (PSP), mixed dementia, and frontotemporal lobar degeneration (FTLD). Epidermal
      growth factor receptor (EGFR) expression was significantly increased in the OB of
      AD and mixed dementia subjects. Moreover, a significant increment in the
      activation of signal transducer and activator of transcription 3 (STAT3) was
      exclusively detected in advanced AD stages, whereas total STAT3 levels were
      specifically overexpressed in mixed dementia. Furthermore, transcription factors
      deregulated in the OB of mixed dementia subjects such as cAMP Responsive Element
      Binding Protein 1 (CREB1) and AP-1 Transcription Factor Subunit (c-Jun) were not
      differentially modulated at olfactory level across AD grading. On the other hand,
      olfactory expression of this signal transducer panel was unchanged in PSP and
      FTLD subjects. Taken together, this study unveils cross-disease similarities and
      differences for specific signal transducers, providing mechanistic clues to the
      intriguing divergence of AD pathology across proteinopathies.

PMID- 29050233
TI  - Clinicopathological characteristics and survival outcomes of male breast cancer
      according to race: A SEER population-based study.
AB  - To investigate the clinicopathological characteristics and survival outcomes of
      breast cancer in the male population, 8,607 cases of patients were identified in
      the Surveillance, Epidemiology, and End Results (SEER) database, including white
      males (n = 7122), black males (n = 1111), and other males (American Indian/AK
      Native, Asian/Pacific Islander) (n = 374). Black male breast cancer patients were
      more likely to be in stages II-IV and have more advanced tumors. The rate of
      lymph node (LN) involvement at diagnosis was higher in black men than in whites
      and others. The ER- and PR-positive rates were lower in black men than in whites
      and others. The distant metastasis rate was higher in blacks than in whites and
      others. Furthermore, the overall survival (OR) rates and breast cancer-specific
      survival rates were significantly poorer in blacks than in whites and others
      (chi2 = 29.974, P < 0.001; chi2 = 7.285, P = 0.026, respectively). In a
      multivariate analysis, the results showed that race could also be a prognostic
      indicator (P < 0.001). Moreover, significant differences were also observed in OS
      among 1:1:1 matched white, black, and other groups (P < 0.001). Differences in
      outcomes may be partially explained by differences in tumor grades, LN status,
      and ER and PR status between the 3 groups. This study might provide insights into
      a better understanding of male breast cancer.

PMID- 29050234
TI  - A small-molecule inhibitor targeting the AURKC-IkappaBalpha interaction decreases
      transformed growth of MDA-MB-231 breast cancer cells.
AB  - The Aurora kinases, Aurora A (AURKA), Aurora B (AURKB), and Aurora C (AURKC), are
      serine/threonine kinases required for the control of mitosis (AURKA and AURKB) or
      meiosis (AURKC). Several Aurora kinase inhibitors are being investigated as novel
      anticancer therapeutics. Recent studies demonstrated that AURKC activation
      contributes to breast cancer cell transformation. Therefore, AURKC is both a
      promising marker and therapeutic target for breast cancer; however, its signaling
      network has not been fully characterized. Using translocation-based cellular
      assays, we identified IkappaBalpha as a binding partner of AURKC, and found that
      AURKC phosphorylates IkappaBalpha at Ser32, thereby activating it. In silico
      modeling and computational analyses revealed a small-molecule inhibitor (AKCI)
      that blocked the AURKC-IkappaBalpha interaction and exerted antitumor activity in
      MDA-MB-231 breast cancer cells. Specifically, AKCI induced G2/M cell-cycle arrest
      through modulation of the p53/p21/CDC2/cyclin B1 pathways. In addition, the drug
      significantly inhibited MDA-MB-231 cell migration and invasion, as well as
      decreasing colony formation and tumor growth. Via its interaction with
      IkappaBalpha, AURKC indirectly induced NF-kappaB activation; accordingly, AKCI
      decreased PMA-induced activation of NF-kappaB. Thus, the small-molecule inhibitor
      AKCI represents a first step towards developing targeted inhibitors of AURKC
      protein binding, which may lead to further advances in the treatment of breast
      cancer.

PMID- 29050235
TI  - Ethnic heterogeneity and prostate cancer mortality in Hispanic/Latino men: a
      population-based study.
AB  - BACKGROUND: Few studies focus on prostate cancer (PCa) outcomes in
      Hispanic/Latino men. Our study explores whether Hispanic/Latino subgroups
      demonstrate significantly different prostate cancer-specific mortality (PCSM)
      relative to Non-Hispanic White (NHW) and Non-Hispanic Black (NHB) men. METHODS:
      We extracted a population-based cohort of men diagnosed with local-regional PCa
      from 2000-2013 (n= 486,865). PCSM was measured in racial/ethnic groups: NHW
      (n=352,886), NHB (n= 70,983), Hispanic/Latino (n= 40,462), and Asian
      American/Pacific Islander (n= 22,534). PCSM was also measured in Hispanic/Latino
      subgroups: Mexican (n= 8,077), Puerto Rican (n= 1,284), South or Central American
      (n= 3,021), Cuban (n= 788), and Dominican (n= 300). We conducted univariable and
      multivariable analyses (MVA) to compare risk for PCSM. RESULTS: Compared to NHW
      men, results showed worse outcomes for NHB men with similar outcomes for
      Hispanic/Latino men. In MVA with NHW men as a reference, NHB (HR= 1.15, p <0.001)
      men had significantly worse PCSM and Hispanic/Latino (HR= 1.02, p= 0.534) men did
      not show a significant difference. In a second MVA, Puerto Rican (HR= 1.71, p
      <0.001) and Mexican (HR= 1.21, p= 0.008) men had significantly higher PCSM. With
      NHB men as a reference, the MVA showed Puerto Rican (HR= 1.50, p= 0.006) men with
      higher PCSM and Mexican (HR= 1.08, p= 0.307) men with no significant difference.
      CONCLUSIONS: Our findings indicate previously unknown disparities in PCSM for
      Puerto Rican and Mexican American men.

PMID- 29050236
TI  - Downregulation of lncRNA MEG3 and miR-770-5p inhibit cell migration and
      proliferation in Hirschsprung's disease.
AB  - The long noncoding RNA (lncRNA) MEG3 is involved in various biological processes
      including cell migration and cell proliferation. In present study, it was found
      that MEG3 and the intronic miR-770-5p were decreased in samples from HSCR
      patients. Besides, knockdown of MEG3 and miR-770-5p suppressed cell migration and
      proliferation, while cell cycle and apoptosis were not affected in human 293T and
      SH-SY5Y cells. SRGAP1 mRNA and protein upregulation was inversely correlated with
      miR-770-5p expression in tissue samples and cell lines, which was confirmed to be
      a target gene of miR-770-5p by dual-luciferase reporter assay. Moreover,
      silencing of SRGAP1 rescued the inhibition of cell migration and proliferation
      induced by MEG3 siRNA and miR-770-5p inhibition. The present study elucidates a
      novel mechanism of the development of HSCR and shows that the MEG3/miR-770
      5p/SRGAP1 pathway plays a vital role in the pathogenesis of HSCR.

PMID- 29050238
TI  - Let-7a inhibits migration, invasion and tumor growth by targeting AKT2 in
      papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy.
      Increasing evidence showed that microRNAs (miRNAs) play an important role in the
      PTC progression. In our study, the result showed that let-7a is significantly
      downregulated in PTC tissues and thyroid cancer cell lines. Overexpression of let
      7a suppressed PTC cell proliferation, migration and invasion. Interestingly, we
      found that AKT2 was a direct target of let-7a and the expression levels of AKT2
      were also observed to inversely correlate with let-7a expression in PTC tissues.
      Furthermore, enhancing AKT2 expression partially reversed the inhibitory effects
      of let-7a in PTC. Taken together, these findings suggest that let-7a acts as a
      novel suppressor by targeting the AKT2 gene and might be a candidate target for
      the development of novel therapeutic strategies to treat papillary thyroid
      carcinoma.

PMID- 29050237
TI  - Modulation of the Nur77-Bcl-2 apoptotic pathway by p38alpha MAPK.
AB  - Orphan nuclear receptor Nur77 promotes apoptosis by targeting mitochondria
      through interaction with Bcl-2, an event that converts Bcl-2 from a survival to
      killer. However, how the Nur77-Bcl-2 apoptotic pathway is regulated remains
      largely unknown. In this study, we examined the regulation of the Nur77-Bcl-2
      pathway by CCE9, a xanthone compound. Our results demonstrated that the apoptotic
      effect of CCE9 depended on its induction of Nur77 expression, cytoplasmic
      localization, and mitochondrial targeting. The activation of the Nur77-Bcl-2
      pathway by CCE9 was associated with its activation of p38alpha MAPK. Inhibition
      of p38alpha MAPK activation by knocking down or knocking out p38alpha MAPK
      impaired the effect of CCE9 on inducing apoptosis and the expression and
      cytoplasmic localization of Nur77. In addition, CCE9 activation of p38alpha MAPK
      resulted in Bcl-2 phosphorylation and Bcl-2 interaction with Nur77, whereas
      inhibition of p38alpha MAPK activation or expression suppressed the interaction.
      Moreover, mutating Ser87 and Thr56 in the loop of Bcl-2, which are known to be
      phosphorylated by p38alpha MAPK, impaired the ability Bcl-2 to interact with
      Nur77. Together, our results reveal a profound role of p38alpha MAPK in
      regulating the Nur77-Bcl-2 apoptotic pathway through its modulation of Nur77
      expression, Bcl-2 phosphorylation, and their interaction.

PMID- 29050239
TI  - Application of in vivo imaging techniques to monitor therapeutic efficiency of
      PLX4720 in an experimental model of microsatellite instable colorectal cancer.
AB  - OBJECTIVES: Patient-derived tumor cell lines are a powerful tool to analyze the
      sensitivity of individual tumors to specific therapies in mice. An essential
      prerequisite for such an approach are reliable quantitative techniques to monitor
      tumor progression in vivo. METHODS: We have employed HROC24 cells, grown
      heterotopically in NMRI Foxn1nu mice, as a model of microsatellite instable
      colorectal cancer to investigate the therapeutic efficiencies of 5'-fluorouracil
      (5'-FU) and the mutant BRAF inhibitor PLX4720, a vemurafenib analogue, by three
      independent methods: external measurement by caliper, magnetic resonance imaging
      (MRI) and positron emission tomography/computed tomography (PET/CT) with 2-deoxy
      2-(18F)fluoro-D-glucose (18F-FDG). RESULTS: Repeated measure ANOVA by a general
      linear model revealed that time-dependent changes of anatomic tumor volumes
      measured by MRI differed significantly from those of anatomic volumes assessed by
      caliper and metabolic volumes determined by PET/CT. Over the investigation period
      of three weeks, neither 5'-FU, PLX4720 nor a combination of both drugs affected
      the tumor volumes. Also, there was no drug effect on the apparent diffusion
      constant (ADC) value as detected by MRI. Interestingly, however, PET/CT imaging
      showed that PLX4720-containing therapies transiently reduced the standardized
      uptake value (SUV), indicating a temporary response to treatment. CONCLUSIONS: 5'
      FU and PLX4720 were largely ineffective with respect to HROC24 tumor growth.
      Tumoral uptake of 18F-FDG, as expressed by the SUV, proved as a sensitive
      indicator of small therapeutic effects. Metabolic imaging by 18F-FDG PET/CT is a
      suitable approach to detect effects of tumor-directed therapies early and even in
      the absence of morphological changes.

PMID- 29050240
TI  - Total flavones of abelmoschus manihot enhances angiogenic ability both in vitro
      and in vivo.
AB  - Angiogenesis is a process of new blood vessel formation from pre-existing
      vessels. It is a normal and vital process in growth and development, as well as
      in wound healing and in the formation of granulation tissue. Total flavones of
      Abelmoschus manihot (TFA) are the major constituents of the traditional Chinese
      herb Abelmoschus manihot L. Medic. The aim of this study is to investigate the
      effect of TFA on angiogenic ability using human umbilical vein endothelial cells
      (HUVECs) in vitro and chick chorioallantoic membrane (CAM) in vivo. HUVECs were
      treated with TFA at different concentrations. Cell viability, cell cycle
      progression, cell apoptosis, cell migration and tubular formation were
      investigated. The expression of vascular endothelial growth factor (VEGF) and
      kinase insert domain receptor (KDR, VEGFR-2) was examined by immunohistochemistry
      to identify mechanism of action of TFA. CAM model was used to evaluate the effect
      of TFA on angiogenesis in vivo. Our results showed that TFA promoted HUVECs
      proliferation in a dose- and time-dependent manner. It increased HUVECs migratory
      ability and the number of tubular structure, promoted vessel formation in HUVECs
      culture and CAM model. Furthermore, TFA treatment resulted in a decrease in cell
      apoptosis and enhanced the expression of VEGF and KDR. Taken together, TFA, as
      the major active component isolated from the traditional Chinese herb Abelmoschus
      manihot L. Medic, could enhance angiogenic ability of HUVECs in vitro and CAM in
      vivo. TFA may be used in the treatment of wound healing and ischemic/reperfusion
      injuries.

PMID- 29050241
TI  - Combination treatment with rucaparib (Rubraca) and MDM2 inhibitors, Nutlin-3 and
      RG7388, has synergistic and dose reduction potential in ovarian cancer.
AB  - Ovarian cancer is the seventh most common cancer worldwide for females and the
      most lethal of all gynecological malignancies. The treatment of ovarian cancer
      remains a challenge in spite of advances in debulking surgery and changes in both
      chemotherapy schedules and routes of administration. Cancer treatment has
      recently been improving with the introduction of targeted therapies to achieve
      greater specificity and less cytotoxicity. Both PARP inhibitors and MDM2-p53
      binding antagonists are targeted therapeutic agents entered into clinical trials.
      This preclinical study evaluated the effect of Nutlin-3/RG7388 and rucaparib as
      single agents and in combination together in a panel of ovarian cancer cell
      lines. Median-drug-effect analysis showed Nutlin-3/RG7388 combination with
      rucaparib was additive to, or synergistic in a cell type-dependent manner.
      Mechanism studies showed rucaparib alone had no effect on p53 stabilization or
      activity. Although treatment with Nutlin-3 or RG7388 induced stabilization of p53
      and upregulation of p21WAF1 and MDM2, the addition of rucaparib did not enhance
      the p53 activation seen with the MDM2 inhibitors alone. These results demonstrate
      that the synergistic effect on growth inhibition observed in the combination
      between rucaparib and Nutlin-3/RG7388 is not the result of increased p53
      molecular pathway activation. Nevertheless, combined treatment of Nutlin-3/RG7388
      with rucaparib increased cell cycle arrest and apoptosis, which was marked for
      A2780 and IGROV-1. These data indicate that combination treatment with MDM2
      inhibitors and rucaparib has synergistic and dose reduction potential for the
      treatment of ovarian cancer, dependent on cell type.

PMID- 29050242
TI  - MiR-34a modulates ionizing radiation-induced senescence in lung cancer cells.
AB  - MicroRNAs (miRNAs) are a new class of gene expression regulators that have been
      implicated in tumorigenesis and modulation of the responses to cancer treatment
      including that of human non-small cell lung cancer (NSCLC). However, the role of
      miR-34a in ionizing radiation (IR)-induced senescence in NSCLC cells remains
      poorly understood. Here we report that IR-induced premature senescence correlates
      with upregulation of miR-34a expression in NSCLC cells. Ectopic overexpression of
      miR-34a by transfection with synthetic miR-34a mimics markedly enhances IR
      induced senescence, whereas inhibition of miR-34a by transfection with a
      synthetic miR-34a inhibitor attenuates IR-induced senescence. Clonogenic assays
      reveal that treatment with miR-34a mimics augments IR-induced cell killing in
      human NSCLC cells. Mechanistically, we found that the senescence-promoting effect
      of miR-34a is associated with a dramatic down-regulation of c-Myc (Myc)
      expression, suggesting that miR-34a may promote IR-induced senescence via
      targeting Myc. In agreement with this suggestion, knockdown of Myc expression by
      RNAi recapitulates the senescence-promoting effect of miR-34a and enhances IR
      induced cell killing in NSCLC cells. Collectively, these results demonstrate a
      previously unrecognized role for miR-34a in modulating IR-induced senescence in
      human NSCLC cells and suggest that pharmacological intervention of miR-34a
      expression may represent a new therapeutic strategy for improving the efficacy of
      lung cancer radiotherapy.

PMID- 29050243
TI  - CANcer-specific Evaluation System (CANES): a high-accuracy platform, for
      preclinical single/multi-biomarker discovery.
AB  - The recent creation of enormous, cancer-related "Big Data" public depositories
      represents a powerful means for understanding tumorigenesis. However, a
      consistently accurate system for clinically evaluating single/multi-biomarkers
      remains lacking, and it has been asserted that oft-failed clinical advancement of
      biomarkers occurs within the very early stages of biomarker assessment. To
      address these challenges, we developed a clinically testable, web-based tool,
      CANcer-specific single/multi-biomarker Evaluation System (CANES), to evaluate
      biomarker effectiveness, across 2,134 whole transcriptome datasets, from 94,147
      biological samples (from 18 tumor types). For user-provided single/multi
      biomarkers, CANES evaluates the performance of single/multi-biomarker candidates,
      based on four classification methods, support vector machine, random forest,
      neural networks, and classification and regression trees. In addition, CANES
      offers several advantages over earlier analysis tools, including: 1) survival
      analysis; 2) evaluation of mature miRNAs as markers for user-defined diagnostic
      or prognostic purposes; and 3) provision of a "pan-cancer" summary view, based on
      each single marker. We believe that such "landscape" evaluation of single/multi
      biomarkers, for diagnostic therapeutic/prognostic decision-making, will be highly
      valuable for the discovery and "repurposing" of existing biomarkers (and their
      specific targeted therapies), leading to improved patient therapeutic
      stratification, a key component of targeted therapy success for the avoidance of
      therapy resistance.

PMID- 29050244
TI  - The prognostic impacts of TEA domain (TEAD) transcription factor polymorphisms in
      Chinese hepatocellular carcinoma patients.
AB  - TEA domain (TEAD) transcription factors play an important role in hepatocellular
      carcinoma (HCC) development and progression by regulating the expression of a
      number of genes. However, the association of their genetic variations with HCC
      prognosis remains elusive. Seven potentially functional single nucleotide
      polymorphisms in TEAD1-4 (rs2304733, rs10831923, rs12104362, rs3745305,
      rs11756089, rs2076173, rs7135838) were genotyped from 331 hepatitis B virus
      positive HCC patients using the Sequenom MassARRAY iPLEX platform. The TEAD3
      rs2076173 C allele and rs11756089 T allele were identified as protective alleles
      as they were significantly associated with longer median overall survival time
      (MST). The T allele of rs2076173 was significantly associated with HCC survival
      independent of age, gender, smoking and drinking status, BCLC stage, and
      chemotherapy or TACE status (HR = 0.73, 95% CI = 0.56-0.93, P = 0.012). This
      protective effect was more prominent for patients who were non-drinkers (P for
      multiplicative interaction = 0.002). Patients had more than one of these
      protective alleles had significant longer MST of 19.25 months than those had none
      (MST=12.85 months, adjusted HR = 0.56, 95% CI = 0.33-0.95, P=0.030), especially
      for those non-drinkers (adjusted HR = 0.48, 95% CI = 0.32-0.74, P = 0.001). These
      findings suggested that rs2076173 and rs11756089 in TEAD3 gene could serve as
      genetic markers for favorable survival in the Chinese HCC patients.

PMID- 29050245
TI  - Von Hippel-Lindau regulates interleukin-32beta stability in ovarian cancer cells.
AB  - Hypoxia-induced interleukin-32beta (IL-32beta) shifts the metabolic program to
      the enhanced glycolytic pathway. In the present study, the underlying mechanism
      by which hypoxia-induced IL-32beta stability is regulated was investigated in
      ovarian cancer cells. IL-32beta expression increased under hypoxic conditions in
      ovarian cancer cells as it did in breast cancer cells. The amount of IL-32beta
      was regulated by post-translational control rather than by transcriptional
      activation. Under normoxic conditions, IL-32beta was continuously eliminated
      through ubiquitin-dependent degradation by the von-Hippel Lindau (VHL) E3 ligase
      complex. Oxygen deficiency or reactive oxygen species (ROS) disrupted the
      interaction between IL-32beta and VHL, leading to the accumulation of the
      cytokine. The fact that IL-32beta is regulated by the energy-consuming
      ubiquitination system implies that it plays an important role in oxidative
      stress. We found that IL-32beta reduced protein kinase Cdelta (PKCdelta)-induced
      apoptosis under oxidative stress. This implies that the hypoxia- and ROS
      stabilized IL-32beta contributes to sustain survival against PKCdelta-induced
      apoptosis.

PMID- 29050246
TI  - NRF2-regulated metabolic gene signature as a prognostic biomarker in non-small
      cell lung cancer.
AB  - Mutations in Kelch-like ECH-associated protein 1 (KEAP1) cause the aberrant
      activation of nuclear factor erythroid-derived 2-like 2 (NRF2), which leads to
      oncogenesis and drug resistance in lung cancer cells. Our study was designed to
      identify the genes involved in lung cancer progression targeted by NRF2. A series
      of microarray experiments in normal and cancer cells, as well as in animal
      models, have revealed regulatory genes downstream of NRF2 that are involved in
      wide variety of pathways. Specifically, we carried out individual and
      combinatorial microarray analysis of KEAP1 overexpression and NRF2 siRNA
      knockdown in a KEAP1 mutant-A549 non-small cell lung cancer (NSCLC) cell line. As
      a result, we identified a list of genes which were mainly involved in metabolic
      functions in NSCLC by using functional annotation analysis. In addition, we
      carried out in silico analysis to characterize the antioxidant responsive element
      sequences in the promoter regions of known and putative NRF2-regulated metabolic
      genes. We further identified an NRF2-regulated metabolic gene signature (NRMGS)
      by correlating the microarray data with lung adenocarcinoma RNA-Seq gene
      expression data from The Cancer Genome Atlas followed by qRT-PCR validation, and
      finally showed that higher expression of the signature conferred a poor prognosis
      in 8 independent NSCLC cohorts. Our findings provide novel prognostic biomarkers
      for NSCLC.

PMID- 29050247
TI  - RNAi-mediated knockdown of Parp1 does not improve the development of female
      cloned mouse embryos.
AB  - Somatic cell nuclear transfer is an important technique for life science
      research, but its efficiency is still extremely low, and most genes that are
      important during early development, such as X chromosome-linked genes, are not
      appropriately expressed during this process. Poly (ADP-ribose) polymerase (PARP)
      is an enzyme that transfers ADP ribose clusters to target proteins. PARP family
      members such as PARP1 participate in cellular signalling pathways through poly
      (ADP-ribosylation) (PARylation), which ultimately promotes changes in chromatin
      structure, gene expression, and the localization and activity of proteins that
      mediate signalling responses. PARP1 is associated with X chromosome inactivation
      (Xi). Here, we showed that abnormal Xi occurs in somatic cell nuclear transfer
      (NT) blastocysts, whereas in female blastocysts derived from cumulus cell nuclear
      transfer, both X chromosomes were inactive. Parp1 expression was higher in female
      NT blastocysts than that in intracytoplasmic sperm injection (ICSI) embryos but
      not in male NT blastocysts. After knocking down Parp1 expression, both the pre
      rRNA 47S and X-inactivation-specific transcript (Xist) levels increased.
      Moreover, the expression of genes on the inactivated X chromosome, such as Magea6
      and Msn, were also increased in the NT embryos. However, the development of
      Parp1si NT embryos was impaired, although total RNA sequencing showed that
      overall gene expression between the Parp1si NT blastocysts and the control was
      similar. Our findings demonstrate that increases in the expression of several
      genes on the X chromosome and of rRNA primary products in NT blastocysts with
      disrupted Parp1 expression are insufficient to rescue the impaired development of
      female cloned mouse embryos and could even exacerbate the associated
      developmental deficiencies.

PMID- 29050248
TI  - Low dose of Bisphenol A enhance the susceptibility of thyroid carcinoma
      stimulated by DHPN and iodine excess in F344 rats.
AB  - Thyroid carcinoma (TC) is the most common endocrine neoplasm. The risk of TC as a
      second primary malignancy (SPM) of breast cancer is significantly increased.
      Bisphenol A (BPA) is a widely contacted xenoestrogen and increases susceptibility
      to breast cancer through binding to estrogen receptor alpha (ERalpha). However,
      the effect of BPA on thyroid carcinogenesis has not been fully demonstrated. This
      present study aimed to characterize the effects of BPA on the development of TC
      using a Fischer 344 (F344) rat model. In this study, we established a TC model
      using female F344 rats pretreated with N-Bis (2-hydroxypropyl) nitrosamine (DHPN)
      at a single dose of 2800 mg/kg (the DA group) or without DHPN (the DN group),
      followed by stimulation with BPA at the level of 250 MUg/kg (BPA250) or 1000
      MUg/kg (BPA1000) and a basic diet containing potassium iodine (KI, 1000 MUg/L)
      for 64 weeks. We demonstrated that the incidence of TC in the BPA250 + KI of DA
      groups reached the highest at 50%, the incidence of thyroid hyperplasia lesions
      (including both tumors and focal hyperplasia lesions) in the BPA1000 + KI of DA
      groups reached 100% (P < 0.05). ERalpha protein and immunochemistry expression
      was upregulated in the BPA-exposed groups and the immunochemistry scores were
      positively correlated with PCNA. Thus, the present results indicate that BPA
      could enhance the susceptibility to TC stimulated by DHPN and iodine excess.
      ERalpha is probably involved in the proliferation effect of BPA. BPA or KI alone
      could not increase TC incidence.

PMID- 29050249
TI  - Profiling cancer-associated genetic alterations and molecular classification of
      cancer in Korean gastric cancer patients.
AB  - Recently, the Cancer Genome Atlas (TCGA) Research Network and Asian Cancer
      Research Group provided a new classification of gastric cancer (GC) to aid the
      development of biomarkers for targeted therapy and predict prognosis. We studied
      associations between genetically aberrant profiles of cancer-related genes,
      environmental factors, and histopathological features in 107 paired gastric tumor
      non-tumor tissue GC samples. 6.5% of our GC cases were classified as the EBV
      subtype, 17.8% as the MSI subtype, 43.0% as the CIN subtype, and 32.7% as the GS
      subtype. The distribution of four GC subgroups based on the TCGA and our dataset
      were similar. The MSI subtype showed a hyper-mutated status and the best
      prognosis among molecular subtype. However, molecular classification based on the
      four GC subtypes showed no significant survival differences in terms of overall
      survival (p= 0.548) or relapse-free survival (RFS, p=0.518). The P619fs*43 in
      ZBTB20 was limited to MSI group (n= 5/19, 26.3%), showing similar trends observed
      in TCGA dataset. Genetic alterations of the RTK/RAS/MAPK and PI3K/AKT/mTOR
      pathways were detected in 34.6% of GC cases (37 individual cases). We also found
      two cases with likely pathogenic variants (NM_004360.4: c. 2494 G>A, p.V832M) in
      the CDH1 gene. Here, we classified molecular subtypes of GC according to the TCGA
      system and provide a critical starting point for the design of more appropriate
      clinical trials based on a comprehensive analysis of genetic alterations in
      Korean GC patients.

PMID- 29050250
TI  - Teriflunomide restores 5-azacytidine sensitivity via activation of pyrimidine
      salvage in 5-azacytidine-resistant leukemia cells.
AB  - Previous studies showed that downregulation of pyrimidine salvage underlies
      resistance against 5-azacytidine (AZA), indicating an important role for de novo
      pyrimidine synthesis in AZA resistance. Because de novo pyrimidine synthesis is
      inhibited by the immunomodulator teriflunomide and its pro-drug leflunomide, we
      examined the effect of combined treatment with AZA and teriflunomide on AZA
      resistance to develop a novel strategy to cancel and prevent AZA resistance.
      Teriflunomide markedly inhibited the growth of AZA-resistant human leukemia cell
      lines (R-U937 and R-HL-60) in comparison with their AZA-sensitive counterparts
      (U937 and HL-60). In the presence of a non-toxic concentration of teriflunomide
      (1 MUM), AZA induced apoptosis in AZA-resistant cells and leukemia cells from AZA
      resistant patients. AZA acted as a DNA methyltransferase 3A inhibitor in AZA
      resistant cells in the presence of 1 MUM teriflunomide. Although AZA-sensitive
      cells acquired AZA resistance after continuous treatment with AZA for 42 days,
      the growth of AZA-sensitive cells continuously treated with the combination of
      AZA and teriflunomide was significantly inhibited in the presence of AZA,
      demonstrating that the combined treatment prevented AZA resistance. These results
      suggest that combined treatment with AZA and teriflunomide can be a novel
      strategy to overcome AZA resistance.

PMID- 29050251
TI  - SF3B1 mutation is a prognostic factor in chronic lymphocytic leukemia: a meta
      analysis.
AB  - Recent studies suggest that SF3B1 might be related to poor prognosis in CLL, but
      the results remain controversial. This meta-analysis was performed to clarify the
      relationship between SF3B1 mutation and prognosis in patients with CLL. The
      relevant published reports were searched in PubMed, EMBASE, and Web of Science. A
      total of 13 articles were included in this meta-analysis as they met the
      inclusion and exclusion criteria. The hazard ratios (HRs) and corresponding 95%
      confidence intervals (95%CIs) for progression free survival (PFS) and/or overall
      survival (OS) were extracted from each eligible study. The pooled HR evaluating
      SF3B1 mutation on PFS was 1.81(95%CI 1.33-2.46, I2=78.9%, P<0.001) and on on OS
      was 2.57(95%CI 1.68-3.94, I2=79.3%, P<0.001) by random effects model. In
      conclusion, SF3B1 mutation was significantly associated with poor PFS and OS in
      CLL. It could be consider as a potential prognostic factor in patients with CLL.

PMID- 29050252
TI  - Opposing roles of ICAT and Wnt/beta-catenin signaling in NSC67657-induced
      monocytic differentiation.
AB  - NSC67657 is a new steroid drug that induces monocytic differentiation of acute
      myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects
      on expression of downstream targets of inhibitor of beta-catenin and TCF (ICAT)
      and Wnt signaling in HL60 cells. ICAT binds to beta-catenin, and this interaction
      is further increased in NSC67657-differentiated cells. ICAT overexpression
      decreases expression of Wnt downstream targets and increases sensitivity of HL60
      cells to NSC67657, while ICAT silencing increases Wnt signaling and delays the
      NSC67657-induced cell differentiation. In addition, pharmacological inhibition of
      Wnt/beta-catenin signaling increases the NSC67657-induced cell differentiation,
      while activation of Wnt/beta-catenin signaling inhibits the differentiation,
      indicating Wnt/beta-catenin signaling inhibits NSC67657-induced monocytic
      differentiation of HL60 cells. Our data demonstrate the opposing roles of ICAT
      and Wnt signaling in the NSC67657-induced monocytic differentiation, and suggest
      that ICAT and Wnt signaling may serve as therapeutic targets for leukemia
      chemotherapy.

PMID- 29050253
TI  - Differential expression of exosomal miRNAs between breast cancer patients with
      and without recurrence.
AB  - BACKGROUND: Exosomal microRNAs (miRNAs) are promising candidate biomarkers for
      diagnosis or prognosis for breast cancer. We investigated the prognostic role of
      exosomal miRNAs in serum samples derived from patients with breast cancer and
      compared miRNA expression between serum and tumor tissues. METHODS: The miRNA
      profile derived from exosome between breast cancer patients with recurrence (n =
      16) and without recurrence (n = 16) were compared by miRNA PCR array. Further, we
      examined the expression of miRNAs derived from tissues in the patients with
      breast cancer with (n = 35) and without recurrence (n = 39) by qRT-PCR. RESULTS:
      Of 384 miRNAs, three miRNAs (miR-338-3p, miR-340-5p, and miR-124-3p) were
      significantly upregulated and eight (miR-29b-3p, miR-20b-5p, miR-17-5p, miR-130a
      3p, miR-18a-5p, miR-195-5p, miR-486-5p, and miR-93-5p) were significantly
      downregulated in the patients with recurrence. We evaluated the expression of the
      miRNAs in tumor tissues. The patients with recurrence had higher levels of miR
      340 at their primary site as well as in the serum. In contrast, miR-195-5p, miR
      17-5p, miR-93-5p, and miR-130a-3p, derived from tumor tissues that were
      downregulated in the serum from patients with recurrence, were higher in the
      patients with recurrence than in those with no recurrence. In logistic regression
      analysis, miR-340-5p, miR-17-5p, miR-130a-3p, and miR-93-5p were significantly
      associated with recurrence. CONCLUSIONS: Several exosomal miRNAs may be useful
      biomarkers to predict breast cancer recurrence. We show the different expression
      patterns of miRNAs between tumor tissues and serum. These findings may suggest
      selective mechanism of release of exosomal miRNAs by cancer cells to regulate
      their progression.

PMID- 29050254
TI  - RGS19 upregulates Nm23-H1/2 metastasis suppressors by transcriptional activation
      via the cAMP/PKA/CREB pathway.
AB  - The Nm23 metastasis suppressor family is involved in physiological and
      pathological processes including tumorigenesis and metastasis. Although the
      inverse correlation of Nm23 level with tumor metastasis potential has been widely
      observed, the mechanisms that regulate the expression of Nm23 remain poorly
      understood. Our previous studies have revealed that Nm23-H1/2 isoforms are
      upregulated by RGS19, a regulator of G protein signaling (RGS) protein which
      accelerates the termination of Gi signals. Here, we examined the ability of RGS19
      to stimulate transcriptional regulation of Nm23 by screening a panel of
      luciferase reporter genes. Transient and stable overexpression of RGS19
      upregulated the Nm23-H1/2 protein levels and activated several transcription
      factors including CREB, AP-1 and SRE in HEK293 cells. Interestingly, agents that
      increase the intracellular cAMP level and the phosphorylation of CREB (e.g.,
      adrenergic receptor agonist, forskolin, and cAMP analogues) upregulated the
      expression of Nm23-H1/2 in HEK293 cells and several cancer cell lines including
      A549, HeLa, MDA-MB-231, and MDA-MB-435s cells. Conversely, inhibition of protein
      kinase A (PKA) by H-89 suppressed the phosphorylation of CREB and reduced the
      expression of Nm23-H1/2. Furthermore, activation of PKA attenuated cancer cell
      migration in wound healing and transwell assays. Collectively, these results
      revealed a PKA-dependent mechanism for controlling Nm23-H1/2 expression.

PMID- 29050255
TI  - Prognostic value of granulocyte colony-stimulating factor in patients with non
      metastatic clear cell renal cell carcinoma.
AB  - Granulocyte colony-stimulating factor is a well-known cytokine to stimulate
      inflammatory cells. We sought to investigate the prognostic value of its
      expression in patients with non-metastatic clear cell renal cell carcinoma.
      Enrolled in this study were 228 eligible patients treated with curative
      nephrectomy for clear cell renal cell carcinoma during 2008. Granulocyte colony
      stimulating factor expression was detected by immunohistochemistry in patient
      specimens, and was divided into three groups according to the distribution of its
      immunohistochemistry score. Subgroup analyses were performed to evaluate its risk
      stratification ability. Cox regression models were applied to analyze the impact
      of prognostic factors. We found that high granulocyte colony-stimulating factor
      expression was associated with diminished recurrence-free survival (P<0.001). Its
      expression had stronger stratification ability in late disease patients, and was
      further identified as an independent prognosticator for recurrence-free survival.
      Moreover, nomogram based on granulocyte colony-stimulating factor expression
      presented a better prognostic ability compared with current prognostic systems
      (the concordance index = 0.874). To conclude, intratumoal granulocyte colony
      stimulating factor expression could be a potential prognosticator for recurrence
      free survival in non-metastatic clear cell renal cell carcinoma patients.
      Incorporating its expression into other pathologic factors provided a finer
      individual model for non-metastatic clear cell renal cell patients.

PMID- 29050256
TI  - In vitro and in vivo effects of suloctidil on growth and biofilm formation of the
      opportunistic fungus Candida albicans.
AB  - As the most frequent fungal pathogen in humans, Candida albicans can develop
      serious drug resistance because its biofilms are resistant to most antifungal
      agents; this leads to an urgent need to develop novel antifungals. Here, we
      evaluated the efficacy of an antithrombotic drug, suloctidil, against C. albicans
      biofilms in vitro and in vivo. We found that suloctidil is effective to inhibit
      C. albicans biofilm, with a minimum inhibitory concentration (MIC80) of 4 MUg/mL,
      a biofilm inhibiting concentration (BIC80) of 16 MUg/mL and a biofilm eradicating
      concentration (BEC80) of 64 MUg/mL. Furthermore, the concentration-dependent
      characteristics of suloctidil were shown by its time-kill curves. Scanning
      electron microscopy images clearly revealed the morphological effects of
      suloctidil on biofilm. Yeast-to-hyphal form switching is a key virulence factor
      of C. albicans; therefore, we performed hyphal growth tests and observed that
      suloctidil inhibited yeast-to-hyphal form switching. This result was consistent
      with the down-regulation of hypha-specific gene (HWP1, ALS3, and ECE1) expression
      levels after suloctidil treatment. In vivo, 256 MUg/mL of suloctidil
      significantly reduced fungal counts (P<0.01) compared to that in groups without
      treatment; the treatment group induced a slight histological reaction, especially
      when the treatment lasted for 5 days (P<0.01). Taken together, our data suggest
      that suloctidil is a potential antifungal agent.

PMID- 29050257
TI  - Linc-ROR induces epithelial-to-mesenchymal transition in ovarian cancer by
      increasing Wnt/beta-catenin signaling.
AB  - Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) is
      an intergenic long non-coding RNA (lncRNA) previously shown to contribute to
      tumorigenesis in several malignancies. However, little is known about whether
      linc-ROR has a role in ovarian cancer progression. In this study, we found that
      linc-ROR expression was increased in high-grade ovarian serous cancer tissues
      compared with normal ovarian tissues or normal fallopian tube tissues.
      Furthermore, the level of linc-ROR expression was associated with ovarian cancer
      International Federation of Gynecology and Obstetrics stage and lymph node
      metastasis. Linc-ROR promoted ovarian cancer cell proliferation both in vitro and
      in vivo, and contributed to cell migration and invasion. Linc-ROR knockdown in
      ovarian cancer cell lines inhibited the epithelial-to-mesenchymal transition
      (EMT) program, which led to ovarian cancer cell metastasis through the repression
      of canonical Wnt/beta-catenin signaling. Together, our results indicated that
      linc-ROR induces EMT in ovarian cancer cells and may be an important molecule in
      the invasion and metastasis of ovarian cancer.

PMID- 29050258
TI  - The diagnostic/prognostic potential and molecular functions of long non-coding
      RNAs in the exosomes derived from the bile of human cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable
      prognosis, and it's difficult to diagnose and no effective treatments are
      available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis
      and metastasis. Intact lncRNAs from exosomes have sparked much interest as
      potential biomarker for the non-invasive analysis of disease. Here, via exosome
      sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis,
      receiver operating characteristic curve and survival analyses, we found that,
      compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1
      showed significantly increased expressions in CCA group. Moreover, area under the
      curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a
      sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher
      levels of the two lncRNAs showed a significantly increasing trend with the
      advancement of cancer TNM stages, and prognosticated a poor survival. In
      addition, KEGG pathway analysis showed that the most significant difference term
      was "p53 signaling pathway" (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs
      and their target genes were included to reconstruct a co-expression network.
      These altered lncRNAs were mainly related to cellular processes, environmental
      information processing and organismal systems, etc. Collectively, our findings
      provided the potential roles of lncRNAs of ENST00000588480.1 and
      ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic
      and therapeutic targets for CCA.

PMID- 29050259
TI  - Characterization of the subcellular localization of Epstein-Barr virus encoded
      proteins in live cells.
AB  - Epstein-Barr virus (EBV) is the pathogenic factor of numerous human tumors, yet
      certain of its encoded proteins have not been studied. As a first step for
      functional identification, we presented the construction of a library of
      expression constructs for most of the EBV encoded proteins and an explicit
      subcellular localization map of 81 proteins encoded by EBV in mammalian cells.
      Viral open reading frames were fused with enhanced yellow fluorescent protein
      (EYFP) tag in eukaryotic expression plasmid then expressed in COS-7 live cells,
      and protein localizations were observed by fluorescence microscopy. As results,
      34.57% (28 proteins) of all proteins showed pan-nuclear or subnuclear
      localization, 39.51% (32 proteins) exhibitted pan-cytoplasmic or subcytoplasmic
      localization, and 25.93% (21 proteins) were found in both the nucleus and
      cytoplasm. Interestingly, most envelope proteins presented pan-cytoplasmic or
      membranous localization, and most capsid proteins displayed enriched or complete
      localization in the nucleus, indicating that the subcellular localization of
      specific proteins are associated with their roles during viral replication. Taken
      together, the subcellular localization map of EBV proteins in live cells may lay
      the foundation for further illustrating the functions of EBV-encoded genes in
      human diseases especially in its relevant tumors.

PMID- 29050260
TI  - Epigenetic silencing of TMEM176A promotes esophageal squamous cell cancer
      development.
AB  - The function of human transmembrane protein 176A (TMEM176A) in cancer remains
      unclear. To understand the function and mechanism of TMEM176A in human esophageal
      cancer development, 13 esophageal cancer cell lines and 267 cases of primary
      esophageal squamous cell cancer (ESCC) samples were analyzed by methylation
      specific PCR (MSP), flow cytometry, immunohistochemistry and transfection assays.
      TMEM176A was highly expressed in BIC1 cells and loss of TMEM176A expression was
      found in TE1, TE3, TE13, KYSE140, KYSE180, KYSE410, KYSE450, KYSE520, Segl,
      KYSE150, YES2 and COLO680N cells. Complete methylation was detected in TE1, TE3,
      TE13, KYSE140, KYSE180, KYSE410, KYSE450, KYSE520, Segl, KYSE150, YES2 and
      COLO680N cells, while unmethylation was detected in BIC1 cells. Restoration of
      TMEM176A expression was induced by 5-aza-2'-deoxycytidine treatment in methylated
      cell lines. TMEM176A was methylated in 66.7% (178/267) of primary esophageal
      cancer samples, and promoter region methylation was significantly associated with
      tumor differentiation (p<0.001) and loss off/reduced expression of TMEM176A
      (p<0.05). Methylation of TMEM176A was significantly associated with poor 5-year
      overall survival (p < 0.05). Cox proportional hazards model analysis suggest that
      TMEM176A methylation is an independent prognostic factor for poor 5-years OS.
      TMEM176A inhibited cell invasion and migration, and induced apoptosis in
      esophageal cancer cells. TMEM176A suppressed esophageal cancer cell growth both
      in vitro and in vivo. In conclusion, TMEM176A is frequently methylated in human
      ESCC and the expression of TMEM176A is regulated by promoter region methylation.
      TMEM176A methylation may serve as a diagnostic and prognostic marker in ESCC.
      TMEM176A is a potential tumor suppressor in human ESCC.

PMID- 29050262
TI  - Longitudinal rotation: a new way to detect the cardiotoxicity of anthracycline
      based chemotherapy in breast cancer patients.
AB  - BACKGROUND AND AIMS: The study was to compare cardiac parameters before and after
      anthracycline-based chemotherapy and identify a parameter for detecting
      cardiotoxicity in breast cancer patients. METHODS: Cardiac function in 43 female
      breast cancer patients was evaluated at three time points: baseline, 1-3 days
      before the initiation of anthracycline-based chemotherapy; 3 weeks and 6 months
      after the final cycle of chemotherapy. At each visit, the peak longitudinal
      velocity; strain rate; peak systolic strain; peak systolic longitudinal
      displacement, and segmental and global longitudinal rotation degrees of the left
      ventricular were measured. RESULTS: The peak early-diastole left ventricular wall
      velocity at baseline was significantly higher than the values at 3 weeks and 6
      months after the final cycle of chemotherapy. The absolute value of the lateral
      wall peak systolic longitudinal rotation degrees was significantly higher at
      baseline than at 3 weeks and 6 months after the final cycle of chemotherapy,
      whereas the absolute value of the global peak systolic longitudinal rotation
      degrees at baseline was significantly lower than the values at 3 weeks and 6
      months after the final cycle of chemotherapy. None of the measured parameters
      differed significantly between the 3 weeks and 6 months after the final cycle of
      chemotherapy. CONCLUSIONS: Cardiac diastolic and systolic dysfunction was found
      after anthracycline-based chemotherapy in this study, and the peak systolic
      longitudinal rotation degrees can be used to detect dysfunction after
      chemotherapy. The cardiotoxicity of epirubicin-based chemotherapy is stronger
      than that of therarubicin-based chemotherapy.

PMID- 29050261
TI  - Alpha-linolenic acid stabilizes HIF-1 alpha and downregulates FASN to promote
      mitochondrial apoptosis for mammary gland chemoprevention.
AB  - Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported
      to have the anti-cancer potential with no defined hypothesis or mechanism/s.
      Henceforth present study was in-quested to validate the effect of alpha linolenic
      acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid
      synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic
      acid was recorded to be 17.55MUM against ER+MCF-7 cells. Treatment with alpha
      linolenic acid was evident for the presence of early and late apoptotic signals
      along with mitochondrial depolarization, when studied through acridine
      orange/ethidium bromide and JC-1 staining. Alpha linolenic acid arrested the cell
      cycle in G2/M phase. Subsequently, the in-vivo efficacy was examined against 7,
      12-dimethylbenz anthracene induced carcinogenesis. Treatment with alpha linolenic
      acid demarcated significant effect upon the cellular proliferation as evidenced
      through decreased in alveolar bud count, restoration of the histopathological
      architecture and loss of tumor micro vessels. Alpha linolenic acid restored the
      metabolic changes to normal when scrutinized through 1H NMR studies. The
      immunoblotting and qRT-PCR studies revealed participation of mitochondrial
      mediated death apoptosis pathway and curtailment of hypoxic microenvironment
      after treatment with alpha linolenic acid. With all above, it was concluded that
      alpha linolenic acid mediates mitochondrial apoptosis, curtails hypoxic
      microenvironment along with inhibition of de novo fatty acid synthesis to impart
      anticancer effects.

PMID- 29050263
TI  - The prognostic value of osteopontin in limited-stage small cell lung cancer
      patients and its mechanism.
AB  - : Osteopontin (OPN) is known to be overexpressed in numerous carcinomas. Although
      abundant OPN has been reported to be correlated with poor survival in non-small
      cell lung cancer (NSCLC) but their clinical and prognostic significance in SCLC
      remains unknown. In this study, RNA-sequencing was used to obtain gene expression
      data in SCLC tissue samples and OPN expression levels were then investigated
      using qPCR, immunohistochemical and Western blot. We found OPN was one of the
      most upregulated genes. Besides, the correlation of OPN with tumor
      clinicopathological characteristics was evaluated and we found OPN was associated
      with advanced tumor stages. In addition, Kaplan-Meier survival analysis and Cox
      analyses revealed OPN expression was an independent predictor for overall
      survival (OS) (P= 0.013) and progression-free survival (PFS) (P=0.008). A high
      level of OPN was correlated with pT classification and pN classification
      (P<0.05). Moreover, In vitro experiments, by test the biological function of OPN
      via colony formation, wound healing, Transwell assays, and western blotting, we
      found that overexpression of OPN induced cell proliferation, migration, and
      invasion; down-regulation of OPN inhibited these. Overexpression of OPN
      stimulates epithelial-mesenchymal transition (EMT) whereas OPN silencing prevents
      the EMT. IN CONCLUSION: OPN appears to contribute to the malignant mechanism of
      SCLC and is a promising and significant prognostic predictor in patients with
      SCLC. Specific silence of OPN could be a future direction to develop a novel
      therapeutic strategy for SCLC patients.

PMID- 29050264
TI  - The microRNA expression signature of pancreatic ductal adenocarcinoma by RNA
      sequencing: anti-tumour functions of the microRNA-216 cluster.
AB  - We analysed the RNA sequence-based microRNA (miRNA) signature of pancreatic
      ductal adenocarcinoma (PDAC). Aberrantly expressed miRNAs were successfully
      identified in this signature. Using the PDAC signature, we focused on 4 clustered
      miRNAs, miR-216a-5p, miR-216a-3p, miR-216b-5p and miR-216b-3p on human chromosome
      2p16.1. All members of the miR-216 cluster were significantly reduced in PDAC
      specimens. Ectopic expression of these miRNAs suppressed cancer cell
      aggressiveness, suggesting miR-216 cluster as anti-tumour miRNAs in PDAC cells.
      The impact of miR-216b-3p (passenger strand of pre-miR-216b) on cancer cells is
      still ambiguous. Forkhead box Q1 (FOXQ1) was directly regulated by miR-216b-3p
      and overexpression of FOXQ1 was confirmed in clinical specimens. High expression
      of FOXQ1 predicted a shorter survival of patients with PDAC by Kaplan-Meier
      analysis. Loss-of-function assays showed that cancer cell migration and invasion
      activities were significantly reduced by siFOXQ1 transfectants. We investigated
      pathways downstream from FOXQ1 by using genome-wide gene expression analysis.
      Identification of the miR-216-3p/FOXQ1-mediated network in PDAC should enhance
      understanding of PDAC aggressiveness at the molecular level.

PMID- 29050265
TI  - Reactive oxygen species dependent phosphorylation of the liver kinase B1/AMP
      activated protein kinase/ acetyl-CoA carboxylase signaling is critically involved
      in apoptotic effect of lambertianic acid in hepatocellular carcinoma cells.
AB  - Though lambertianic acid (LA) is reported to have hypolipidemic activity in
      liver, its underlying anticancer mechanism is poorly understood so far. Thus, in
      the present study, apoptotic mechanism of LA was elucidated in HepG2 and SK-Hep1
      hepatocellular carcinoma (HCC) cells. Here LA increased cytotoxicity, sub-G1
      population and Annexin V/PI positive cells in two HCC cells. Also, LA cleaved
      caspase-3 and poly(ADP-ribose) polymerase (PARP), activated phosphorylation of
      liver kinase B1 (LKB1)/AMP activated protein kinase (AMPK)/ acetyl-CoA
      carboxylase (ACC) pathway and also suppressed antiapoptotic proteins such as
      phosphorylation of Akt/ mammalian target of rapamycin (mTOR) and the expression
      of B cell lymphoma-2 (Bcl-2)/ B-cell lymphoma-extra large (Bcl-xL) and
      cyclooxygenase-2 (COX-2) in two HCC cells. Furthermore, LA generated reactive
      oxygen species (ROS) in HepG2 cells and AMPK inhibitor compound C or ROS
      inhibitor N-acetyl-L-cysteine (NAC) blocked the apoptotic ability of LA to cleave
      PARP or increase sub G1 population in HepG2 cells. Consistently, cleavages of
      PARP and caspase-3 were induced by LA only in AMPK+/+ MEF cells, but not in AMPK
      /- MEF cells. Also, immunoprecipitation (IP) revealed that phosphorylation of
      LKB1/AMPK through their binding was enhanced in LA treated HepG2 cells. Overall,
      these findings suggest that ROS dependent phosphorylation of LKB1/AMPK/ACC
      signaling is critically involved in LA induced apoptosis in HCCs.

PMID- 29050266
TI  - Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian
      cancer cells through STAT3 signaling.
AB  - Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and
      subsequent resistance to chemotherapy have become major obstacles to treating
      these diseases. In the present study, we showed that a natural withanolide
      isolated from the plant Physalis pubescens L. (Solanaceae), Physapubescin B,
      exhibited potent anti-tumor activity against ovarian cancer cells. Physapubescin
      B promoted apoptosis, induced cell-cycle arrest and inhibited invasion of ES-2
      and A2780 cells. Physapubescin B treatment also resulted in suppression of the
      transcriptional activity of STAT3, an oncogenic transcription factor activated in
      many human malignancies including ovarian cancer, through disturbing the
      dimerization of STAT3, and thereby inhibited the nuclear translocation of
      Tyr705/Ser727-phosphorylated STAT3. The IL-6-stimulated activation of STAT3 and
      its downstream genes Cyclin D1, survivin, and Bcl-xL was also repressed by
      Physapubescin B. Furthermore, Physapubescin B sensitizes A2780 cells to taxol
      induced cell growth inhibition in vitro. These findings strongly suggest that
      Physapubescin B has potential antitumor activity and may circumvent taxol
      resistance in human ovarian cancer cells through inhibition of aberrant
      activation of STAT3.

PMID- 29050267
TI  - Reversible regulation of ORC2 SUMOylation by PIAS4 and SENP2.
AB  - The small ubiquitin-related modifier (SUMO) system is essential for smooth
      progression of cell cycle at the G2/M phase. Many centromeric proteins are
      reversibly SUMOylated to ensure proper chromosome segregation at the mitosis.
      SUMOylation of centromeric Origin Recognition Complex subunit 2 (ORC2) at the
      G2/M phase is essential in maintaining genome integrity. However, how ORC2
      SUMOylation is regulated remains largely unclear. Here we show that ORC2
      SUMOylation is reversibly controlled by SUMO E3 ligase PIAS4 and De-SUMOylase
      SENP2. Either depletion of PIAS4 or overexpression of SENP2 eliminated
      SUMOylation of ORC2 at the G/M phase and consequently resulted in abnormal
      centromeric histone H3 lysine 4 methylation. Cells stably expressing SENP2
      protein or small interfering RNA for PIAS4 bypassed mitosis and endoreduplicated
      their genome to become polyploidy. Furthermore, percentage of polyploid cells is
      reduced after coexpression of ORC2-SUMO2 fusion protein. Thus, the proper
      regulation of ORC2 SUMOylation at the G2/M phase by PIAS4 and SENP2 is critical
      for smooth progression of the mitotic cycle of cells.

PMID- 29050268
TI  - Long non-coding RNA NEAT1 regulates epithelial membrane protein 2 expression to
      repress nasopharyngeal carcinoma migration and irradiation-resistance through miR
      101-3p as a competing endogenous RNA mechanism.
AB  - The altered expression of long non-coding RNAs (lncRNAs) is often related to
      carcinogenesis, metastasis and resistance to radiation or chemotherapy. In the
      current study, cDNA microarray analysis found that NEAT1 expression was reduced
      in nasopharyngeal carcinoma (NPC) patients and that it regulated NPC progression.
      However, the detailed mechanisms of NEAT1 in NPC were unclear. NEAT1 repressed
      NPC cell growth, invasion and radiation resistance in vitro and tumor metastasis
      in vivo. In addition, the results of an approach integrating bioinformatics,
      luciferase reporter assays and RNA immunoprecipitation indicated that NEAT1
      antagonized miR-101-3p through a competing endogenous RNA (ceRNA) mechanism and
      that the interaction between NEAT1 and EMP2 was miR-101-3p dependent. Our results
      showed a novel connection of NEAT1, miR-101-3p and EMP2 in NPC migration and
      radiation resistance.

PMID- 29050269
TI  - Long non-coding RNA CARLo-5 promotes tumor progression in hepatocellular
      carcinoma via suppressing miR-200b expression.
AB  - Long non-coding RNAs (lncRNAs) play key roles in cancer initiation and
      progression. The aim was to investigate the biological functions and clinical
      significance of long non-coding RNA CARLo-5 in hepatocellular carcinoma (HCC).
      QRT-PCR was performed to investigate CARLo-5 expression in HCC tissues and cells.
      Kaplan-Meier curve and multivariate analysis validated the association between
      CARLo-5 expression and overall survival (OS) in HCC patients. Cell proliferation
      and invasion was performed by CCK8 cell proliferation, cell colony formation and
      transwell invasion assays. Western-blot assay was performed to evaluate the
      protein expression of Twist1, ZEB1, E-cadherin and Vimentin. Tumor xenografts
      were performed to evaluate the effect of CARLo-5 on tumor growth in vivo. RNA
      Immunoprecipitation (RIP) and Chromatin Immunoprecipitation (ChIP) were also
      performed. Our results showed that CARLo-5 expression was significantly higher in
      HCC tissues and upregulated CARLo-5 expression was closely correlated with tumor
      size and advanced tumor stage. Kaplan-Meier curve and multivariate analysis
      validated that higher CARLo-5 expression predicted a poor prognosis for HCC
      patients and was an independent risk factor for OS in HCC patients. In vitro,
      knockdown of CARLo-5 inhibited cell proliferation, colony formation, cell
      invasion and inhibited the cell epithelial-mesenchymal transition (EMT) by up
      regulating the E-cadherin expression and down-regulating Twist1, ZEB1 and
      vimentin expression in HCC cells. Furthermore, we demonstrated that CARLo-5
      inhibited the miR-200b expression via EZH2. In vivo, knockdown of CARLo-5
      significantly inhibited the tumor growth. Thus, our results indicated that CARLo
      5 represented a novel tumor biomarker and therapeutic target for HCC.

PMID- 29050270
TI  - KIT performed as a driver gene candidate affecting the survival status of
      patients with stomach adenocarcinoma.
AB  - Stomach adenocarcinoma is estimated to cause 10,000 deaths in the US in 2016 and
      is the third most deadly cancer in China. We aim to identify the proteins and the
      genes that have impact on the prognosis of patients with stomach adenocarcinoma.
      Data of patients with stomach adenocarcinoma were retrieved from The Cancer
      Genome Atlas (TCGA). Proteins whose expression levels were highly correlated with
      survival status of patients were figured out. The expression levels of their
      mRNAs and their roles in the pathway were used to determine the driver gene
      candidates. The effects of mutations on the genes encoding KIT on mRNA
      expressions were carried. Ten antibodies were figured out to have significant
      correlation with stomach cancer prognosis. The coefficients of COXPH models
      matches their roles in the previous studies. The expression levels of mRNAs
      versus proteins suggested that KIT might act as a driver gene, which was also the
      central in the pathway of other selected proteins. The missense mutations on the
      gene encoding KIT led to the low expression of its mRNAs and there were much
      fewer nonsense mutations compared with other genes. It suggested that the
      important role of KIT as an oncogene in the progression of cancer, as well as a
      tyrosine-protein kinase during the normal activity. Ten antibodies, corresponding
      to fifteen proteins, were highly correlated with patients' survival time, within
      which KIT played a critical roles. It suggested that KIT might be used as
      biomarker or as target of cancer therapies.

PMID- 29050271
TI  - Sesquiterpene binding Gly-Leu-Ser/Lys-"co-adaptation pocket" to inhibit lung
      cancer cell epithelial-mesenchymal transition.
AB  - Sesquiterpene lactones (SL) have a wide range of applications in anti-tumor and
      anti-inflammatory therapy. However, the pharmacological mechanism of such
      substances is not clear. In this study, parthenolide (PTL) was used as an example
      to explore the anti-tumor effect of natural molecules and their common mechanism.
      We showed that PTL inhibited the proliferation and migration by reverse EMT via
      the ERK2/NF-kappaB/Snail pathway in vivo and in vitro. Interestingly, Multiple
      potential targets of PTL contain a Gly-Leu-Ser/Lys-"co-adaptation pocket". This
      inspiring us analogies of PTL may also bind to these target proteins and play a
      similar function. Significantly, the Concept of co-adaptation pocket may help to
      increase the selectivity of drug research and development.

PMID- 29050272
TI  - Impact of marital status on renal cancer patient survival.
AB  - Marital status is an independent prognostic factor for various cancer types. The
      present study used the Surveillance, Epidemiology, and End Results (SEER)
      database of the National Cancer Institute (NCI) to analyze the impact of marital
      status on renal cancer patient survival outcomes. We identified a total of 62,405
      eligible patients (23,800 women and 38,605 men). Overall 5-year renal cancer
      cause-specific survival (CSS) was 80.3% in the married group, 69.2% in the
      widowed group, 78.9% in the single group, and 76.5% in the divorced/separated
      group. The widowed patient group had the highest female/male ratio, more distant
      metastases, and fewer high-grade (III/IV) tumors. Most widowed patients (90.4%)
      were elderly (>60 years old). In our study, male renal cancer patients benefited
      more from marriage than females. We also found that white married patients had
      better survival outcomes than other white patient groups, but black unmarried and
      married patients exhibited similar survival outcomes. Our results show that, in
      general, unmarried patients have higher rates of cancer-specific mortality and
      highlight the importance of psychological intervention for cancer patients during
      treatment.

PMID- 29050273
TI  - TGFbeta induced factor homeobox 1 promotes colorectal cancer development through
      activating Wnt/beta-catenin signaling.
AB  - Colorectal cancer (CRC) is one of the most common cancers, but the mechanisms
      underlying its initiation and progression are largely unknown. TGIF1 (TGFB
      induced factor homeobox 1) is a transcriptional corepressor that belongs to the
      three-amino acid loop extension (TALE) superclass of atypical homeodomains. It
      has been reported that TGIF1 is highly expressed in mammary cancer and non-small
      cell lung cancer and can enhance tumor progression. However, the role of TGIF1 in
      colorectal cancer remains unknown. Here, we report that TGIF1 is significantly
      upregulated in colorectal cancers, and its high expression predicts poor
      prognosis. Overexpression of TGIF1 markedly promotes the proliferation of
      colorectal cancer cells both in vivo and in vitro. In addition, TGIF1 activates
      Wnt/beta-catenin signaling, and the homeodomain is indispensable for Wnt
      activation and beta-catenin interaction. Taken together, our results suggest that
      TGIF1 is a novel colorectal tumor promoter and indicate that TGIF1 enhances
      colorectal cancer tumorigenesis through activating Wnt signaling.

PMID- 29050274
TI  - Apparent diffusion coefficient histogram analysis can evaluate radiation-induced
      parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.
AB  - We investigated apparent diffusion coefficient (ADC) histogram analysis to
      evaluate radiation-induced parotid damage and predict xerostomia degrees in
      nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of
      bilateral parotid glands in NPC patients was conducted 2 weeks before
      radiotherapy (time point 1), one month after radiotherapy (time point 2), and
      four months after radiotherapy (time point 3). From time point 1 to 2, parotid
      volume, skewness, and kurtosis decreased (P < 0.001, = 0.001, and < 0.001,
      respectively), but all other ADC histogram parameters increased (all P < 0.001,
      except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid
      volume continued to decrease (P = 0.022), and SD, 75th and 90th percentiles
      continued to increase (P = 0.024, 0.010, and 0.006, respectively). Early change
      rates of parotid ADCmean, ADCmin, kurtosis, and 25th, 50th, 75th, 90th
      percentiles (from time point 1 to 2) correlated with late parotid atrophy rate
      (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis
      revealed correlations among parotid volume, time point, and ADC histogram
      parameters. Early mean change rates for bilateral parotid SD and ADCmax could
      predict late xerostomia degrees at seven months after radiotherapy (three months
      after time point 3) with AUC of 0.781 and 0.818 (P = 0.014, 0.005, respectively).
      ADC histogram parameters were reproducible (intraclass correlation coefficient,
      0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation
      induced parotid damage noninvasively, and predict late xerostomia degrees of NPC
      patients treated with radiotherapy.

PMID- 29050275
TI  - Alisol B 23-acetate induces autophagic-dependent apoptosis in human colon cancer
      cells via ROS generation and JNK activation.
AB  - Alisol B 23-acetate (AB23A), a natural triterpenoid from the rhizome of Alisma
      orientale, a Chinese medicinal herb, has multiple physiological activities
      including anticancer. However, its effect on human colon cancer and the
      underlying mechanism are not clear. Here, we reported for the first time that
      AB23A induced cell cycle G1 phase arrest and apoptotic cell death in colon cancer
      cells. Autophagy also occurred in AB23A-treated HCT116 cells as evidenced by the
      accumulation of microtubule-associated protein 1 light chain 3 form II (LC3-II)
      and degradation of SQSTM1/p62. An autophagy inhibitor, 3-methyladenine (3-MA) was
      found to attenuate AB23A-mediated autophagy, apoptosis, and cell death,
      indicating that AB23A-induced apoptotic response was dependent on the induction
      of autophagy. In addition, the treatment of HCT116 cells with AB23A resulted in
      the generation of reactive oxygen species (ROS) and phosphorylation of c-Jun N
      terminal kinase (JNK). A ROS scavenger, N-acetylcysteine (NAC) and a JNK-specific
      inhibitor, SP600125 attenuated AB23A-induced autophagy and apoptotic cell death.
      Moreover, NAC was able to eliminate AB23A-induced JNK phosphorylation. This
      finding provides a novel mechanism of action of AB23A in colon cancer HCT116
      cells that AB23A induces autophagic-dependent apoptotic cell death in colon
      cancer cells, at least in part, though the accumulation of intracellular ROS and
      subsequent activation of JNK.

PMID- 29050276
TI  - A new donors' CYP3A5 and recipients' CYP3A4 cluster predicting tacrolimus
      disposition, and new-onset hypertension in Chinese liver transplant patients.
AB  - AIM: The purpose of the current study was to investigate individualized therapy
      of tacrolimus (Tac), as well as complications after liver transplantation (LT)
      with the known genetic determinants and clinical factors. METHODS: In this
      retrospective study, two cohorts (n=170) from the China Liver Transplant Registry
      (CLTR) database from July 2007 to March 2015 were included. RESULTS: Both donors'
      CYP3A5*3 and recipients' CYP3A4*1G had a correlation with Tac pharmacokinetics at
      four weeks (all P<0.05), except recipients' CYP3A4*1G nearly had an association
      at week 2 (P=0.055). The model of donors' CYP3A5*3, recipients' CYP3A4*1G, and
      total bilirubin (TBL), for the prediction of Tac disposition, was better than
      donors' CYP3A5*3 only at week 1, 2, and 3 (P=0.010, P=0.007, and P=0.010,
      respectively), but not apparent at week 4 (P=0.297). Besides, when the P value
      was greater than or equal to 0.6685 after considering the false-positive rate
      R=10%, the patients were considered to have a faster metabolism, according to the
      mentioned model. Interestingly, we found that if more than or equal to two
      alleles A were present in the combination of donors' CYP3A5*3 and recipients'
      CYP3A4*1G genotype, there was a lower Tac C/D ration at week 1, 2, and 3
      (P<0.001, P=0.001, and P<0.001), except at week 4 (P=0.082), and the probability
      of new-onset hypertension was lesser (P<0.001). CONCLUSIONS: These data provided
      a potential basis for a comprehensive approach to predicting the Tac dose
      requirement in individual patients and provided a strategy for the effective
      prevention, early diagnosis of new-onset hypertension in Chinese LT recipients.

PMID- 29050277
TI  - The clinical significance of HPIP and the associated prognosis in cervical
      cancer.
AB  - Hematopoietic pre-B-cell leukemia transcription factor-interacting protein
      (HPIP), is known to promote tumor development and metastasis. However its role in
      cervical cancer remains unknown. The purpose of this study was to investigate the
      clinical significance of HPIP expression and the prognosis of patients with
      cervical cancer. Fresh frozen tissues from 10 samples of cervical cancer and
      8normal cervical tissues were analyzed for HPIP expression using real-time
      reverse transcription PCR and Western blot analysis. A total of 129 paraffin
      embedded surgical specimens from patients with CC were collected for an
      immunohistochemistry assay to measure HPIP expression. Correlations of HPIP
      expression with clinicopathological factors and prognosis of patients with
      cervical cancer were analyzed. The HPIP expression at both the mRNA and protein
      levels was significantly higher in cervical cancer tissues than in normal
      cervical tissues (P<0.001). HPIP overexpression was significantly associated with
      high FIGO stage (P=0.005), Histological grade (P<0.001), Ascular tumor embolus
      (P=0.004), Iinterstitial infiltration (P<0.001), Tumor size (P=0.001) and Lymph
      node metastasis (P=0.005). Moreover, results revealed that HPIP expression was an
      independently prognostic factor for both overall survival [hazard ratio (HR):
      8.874; 95% CI: 1.186-66.393; P=0.033] and disease-free survival [(HR): 11.523;
      95% CI: 1.531-86.746; P=0.018] in patients with cervical cancer. The present
      study provides evidence that HPIP predicts metastasis and poor survival,
      highlighting its potential function as a therapeutic target for cervical cancer.

PMID- 29050278
TI  - Identification of core genes and outcome in gastric cancer using bioinformatics
      analysis.
AB  - Gastric cancer (GC) is a common malignant neoplasm of gastrointestinal tract. We
      chose gene expression profile of GSE54129 from GEO database aiming to find key
      genes during the occurrence and development of GC. 132 samples, including 111
      cancer and 21 normal gastric mucosa epitheliums, were included in this analysis.
      Differentially expressed genes (DEGs) between GC patients and health people were
      picked out using GEO2R tool, then we performed gene ontology (GO) analysis and
      Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis using The Database
      for Annotation, Visualization and Integrated Discovery (DAVID). Moreover,
      Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and
      Molecular Complex Detection (MCODE) plug-in was utilized to visualize protein
      protein interaction (PPI) of these DEGs. There were 971 DEGs, including 468 up
      regulated genes enriched in focal adhesion, ECM-receptor interaction and PI3K-Akt
      signaling pathway, while 503 down-regulated genes enriched in metabolism of
      xenbiotics and drug by cytochrome P450, chemical carcinogenesis, retinol
      metabolism and gastric acid secretion. Three important modules were detected from
      PPI network using MCODE software. Besides, Fifteen hub genes with high degree of
      connectivity were selected, including BGN, MMP2, COL1A1, and FN1. Moreover, the
      Kaplan-Meier analysis for overall survival and correlation analysis were applied
      among those genes. In conclusion, this bioinformatics analysis demonstrated that
      DEGs and hub genes, such as BGN, might promote the development of gastric cancer,
      especially in tumor metastasis. In addition, it could be used as a new biomarker
      for diagnosis and to guide the combination medicine of gastric cancer.

PMID- 29050280
TI  - Standardized tumor volume: an independent prognostic factor in advanced
      nasopharyngeal carcinoma.
AB  - The study evaluated the prognostic effect of standardized tumor volume in
      patients with advanced nasopharyngeal carcinoma (NPC) treated with concurrent
      chemoradiotherapy. Between Jan 1, 2009 and December 30, 2012, 143 patients
      diagnosed with NPC in UICC stage III-IVb by histopathology were enrolled in the
      study. These patients underwent intensity-modulated radiotherapy combined with
      concurrent chemotherapy. The three-dimensional images of tumor volume were
      reconstructed automatically by the treatment planning system. SGTVnx was
      calculated based on GTVnx/person's volume. SGTVnd was calculated based on
      GTVnd/person's volume. SGTVnx was significantly associated with the 5-year
      overall survival (OS), disease-free survival (DFS), DMFS, and LRFS rates in
      univariate and multivariate analyses. Although SGTVnd was associated with the 5
      year OS, DFS, and DMFS rates, it was not an independent prognostic factor for
      LRFS. In receiver operating characteristic (ROC) curve analysis, 1.091 and 0.273
      were determined as the cut-off points for SGTVnx and SGTVnd, respectively. The 5
      year OS, DFS, DMFS, and LRFS rates for patients with a SGTVnx > 1.091 vs. SGTVnx
      <= 1.091 was 65.4% vs. 93.4% (P < 0.001), 65.2% vs. 94.8% (P < 0.001), 71.4% vs.
      97.4% (P < 0.001), and 84.8% vs. 97.3% (P = 0.003), respectively, for SGTVnd >
      0.273 vs. SGTVnd <= 0.273 was 70.3% vs. 96.5% (P < 0.001), 70.1% vs. 94.8% (P <
      0.001), 77.5% vs. 98.2% (P < 0.001), and 88.5% vs. 96.6% (P = 0.049),
      respectively. UICC stage grouping, T classification, N classification, and sex
      were not found to be independent prognostic factors for NPC. Standardized tumor
      volume was an independent prognostic factor for NPC that might improve the
      current NPC TNM classification system and provide new clinical evidence for
      personalized treatment strategies.

PMID- 29050279
TI  - SSeCKS/AKAP12 scaffolding functions suppress B16F10-induced peritoneal metastasis
      by attenuating CXCL9/10 secretion by resident fibroblasts.
AB  - SSeCKS/Gravin/AKAP12 (SSeCKS) is a kinase scaffolding protein known to suppress
      metastasis by attenuating tumor-intrinsic PKC- and Src-mediated signaling
      pathways [1]. In addition to downregulation in metastatic cells, in silico
      analyses identified SSeCKS downregulation in prostate or breast cancer-derived
      stroma, suggesting a microenvironmental cell role in controlling malignancy.
      Although orthotopic B16F10 and SM1WT1[BrafV600E] mouse melanoma tumors grew
      similarly in syngeneic WT or SSeCKS-null (KO) mice, KO hosts exhibited 5- to 10
      fold higher levels of peritoneal metastasis, and this enhancement could be
      adoptively transferred by pre-injecting naive WT mice with peritoneal fluid (PF),
      but not non-adherent peritoneal cells (PC), from naive KO mice. B16F10 and SM1WT1
      cells showed increased chemotaxis to KO-PF compared to WT-PF, corresponding to
      increased PF levels of multiple inflammatory mediators, including the Cxcr3
      ligands, Cxcl9 and 10. Cxcr3 knockdown abrogated enhanced chemotaxis to KO-PF and
      peritoneal metastasis in KO hosts. Conditioned media from KO peritoneal membrane
      fibroblasts (PMF), but not from KO-PC, induced increased B16F10 chemotaxis over
      controls, which could be blocked with Cxcl10 neutralizing antibody. KO-PMF
      exhibited increased levels of the senescence markers, SA-beta-galactosidase,
      p21waf1 and p16ink4a, and enhanced Cxcl10 secretion induced by inflammatory
      mediators, lipopolysaccharide, TNFalpha, IFNalpha and IFNgamma. SSeCKS
      scaffolding-site mutants and small molecule kinase inhibitors were used to show
      that the loss of SSeCKS-regulated PKC, PKA and PI3K/Akt pathways are responsible
      for the enhanced Cxcl10 secretion. These data mark the first description of a
      role for stromal SSeCKS/AKAP12 in suppressing metastasis, specifically by
      attenuating signaling pathways that promote secretion of tumor chemoattractants
      in the peritoneum.

PMID- 29050281
TI  - IL-23R and IL-17A polymorphisms correlate with susceptibility of ankylosing
      spondylitis in a Southwest Chinese population.
AB  - The association between the IL-23R and IL-17A polymorphisms and ankylosing
      spondylitis (AS) in the Southwest Chinese Population is still unclear. The
      purpose of this study is to detect the association between IL-23R and IL-17A
      polymorphisms and AS. A case-control study consisting of 486 AS patients and 480
      healthy controls was performed. We used the high-resolution melting methods (HRM)
      to genotype five selected single nucleotide polymorphisms (SNPs), rs6693831,
      rs7517847, rs1884444, rs10889677 in the IL-23R gene and rs2275913 in the IL-17A
      gene. Meanwhile, the laboratory indexes were recorded. In this study, patients
      with genotype CC (p = 8.574E-8) and allele C (p = 3.206E-31) on SNP rs6693831 (IL
      23R) showed decreased risk of AS. The genotype TT (p = 4.551E-6) and allele T (p
      = 0.02) on SNP rs1884444 (IL-23R) showed significant lower risk of AS.
      Individuals carrying the allele A of rs2275913 showed higher morbidity of AS (p =
      0.04). We first detected that rs6693831 and rs1884444 in IL-23R gene and
      rs2275913 in IL-17A gene have genetic association with AS.

PMID- 29050282
TI  - Effective antitumor peptide vaccines can induce severe autoimmune pathology.
AB  - Immunotherapy has shown a tremendous success in treating cancer. Unfortunately,
      this success is frequently associated with severe autoimmune pathology. In this
      study, we used the transgenic RIP-gp mouse model to assess the antitumor
      therapeutic benefit of peptide vaccination while evaluating the possible
      associated autoimmune pathology. We report that palmitoylated gp33-41 peptide and
      poly-IC adjuvant vaccine (BiVax) generated ~ 5-10 % of antigen specific T cell
      responses in wild type and supposedly immune tolerant RIP-gp mice. Boosting with
      BiVax in combination with alphaCD40 antibody (TriVax) or BiVax in combination
      with IL-2/alphaIL-2 antibody complexes (IL2Cx) significantly increased the immune
      responses (~30-50%). Interestingly, although both boosts were equally effective
      in generating vast T cell responses, BiVax/IL2Cx showed better control of tumor
      growth than TriVax. However, this effect was associated with high incidence of
      diabetes in an antigen and CD8 dependent fashion. T cell responses generated by
      BiVax/IL2Cx, but not those generated by TriVax were highly resistant to PD-1/PD
      L1 inhibitory signals. Nevertheless, PD-1 blockade enhanced the ability of TriVax
      to control tumor growth but increased the incidence of diabetes. Finally, we show
      that severe autoimmunity by BiVax/IL2Cx was prevented while preserving
      outstanding antitumor responses by utilizing a tumor antigen not expressed in the
      pancreas. Our data provides a clear evidence that peptide based vaccines can
      expand vast endogenous T cell responses which effectively control tumor growth
      but with high potential of autoimmune pathology.

PMID- 29050283
TI  - Omeprazole promotes carcinogenesis of fore-stomach in mice with co-stimulation of
      nitrosamine.
AB  - OBJECTIVES: To investigate if oral omeprazole application induces cancers of fore
      and glandular stomach in mice. METHODS: A total of 66 eligible male mice were
      randomly divided into 6 groups, which were treated with control reagent, low (6
      mg/kg) and high dose omeprazole (30 mg/kg), N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG, 100 mg/L water), and MNNG plus low and high dose omeprazole, respectively.
      After 24 weeks, concentrations of acid phosphatase (ACP) and N-acetyl-beta-D
      glucosaminidase(NAG) in serum and spleen was examined, and p21 and mTOR levels in
      stomach were detected. RESULTS: The mouse spleen weight index was smaller in the
      omeprazole group than the control group, and in the MNNG plus omeprazole groups
      than the MNNG group. In the fore-stomach, more carcinomas were observed in the
      MNNG plus omeprazole groups than in the MNNG group. In the glandular stomach,
      there existed more atypical hyperplasia cases in the MNNG plus omeprazole groups
      than the MNNG-treated group, and one carcinoma was induced in the MNNG plus high
      dose omeprazole group. Omeprazole alone caused minor gastric pathological
      changes. Omeprazole treatment lowered both serum and spleen ACP and NAG levels in
      both the non-MNNG-treated and MNNG-treated subgroups. In fore-stomach, there
      existed decreased p21 and mTOR levels in the omeprazole-treated groups than in
      the control group, and in the MNNG plus omeprazole groups than the MNNG-treated
      group. CONCLUSION: Omeprazole promotes carcinogenesis of the mouse fore-stomach
      but not the glandular stomach following treatment with MNNG. Lysosomal hydrolase
      activity was inhibited and some cancer-associated proteins was dysregulated,
      which requires further explorations.

PMID- 29050284
TI  - Mutational analysis of a Chinese family with oculocutaneous albinism type 2.
AB  - Oculocutaneous albinism (OCA) is an autosomal recessive disorder characterized by
      hypopigmentation of the skin, hair, and eyes accompanied with ophthalmologic
      abnormalities. Molecular genetic test can confirm the diagnosis of the four
      subtypes of OCA (OCA1-4). Herein, we report a Chinese family with two patients
      affected by OCA. Mutations of TYR, OCA2, TYRP1, and SLC45A2 were examined by
      using PCR-sequencing. Large deletions or duplications of TYR and OCA2 were
      examined by Multiplex Ligation-dependent Probe Amplification (MLPA) assay.
      Compound heterozygous mutations of OCA2, (c.808-3C>G and c.2080-2A>G), were
      identified in both patients characterized with yellow hair and milky skin,
      heterochromia iridis, and nystagmus. Several computer-assisted approaches
      predicted that c.808-3C>G and c.2080-2A>G in OCA2 might potentially be pathogenic
      splicing mutations. No exon rearrangement (deletion/duplication) of TYR and OCA2
      was observed in the patients by MLPA analysis. This study suggests that compound
      heterozygous mutations, (c.808-3C>G and c.2080-2A>G), in OCA2 may be responsible
      for partial clinical manifestations of OCA.

PMID- 29050285
TI  - High-dose atorvastatin reduces the risk of cardiovascular events in patients with
      percutaneous coronary intervention.
AB  - We systematically searched in PubMed, Web of Science, Embase and China National
      Knowledge Infrastructure from the inception to March 31, 2017, identified
      relevant trials about efficacy of high-does Atorvastatin for patients with
      percutaneous coronary intervention. Twelve studies with the number of 2801
      patients were included in the meta-analysis. Compared with control group, high
      does Atorvastatin significantly reduced the risk of myocardial infarction in
      patients with percutaneous coronary intervention (Relative risk =0.62, 95%
      confidence interval: 0.49-0.78), with low level of heterogeneity (I2=22.6%,
      P=0.228). Nine studies with 2248 patients reported the adverse cardiovascular
      events. A fixed-effect model was applied. Compared with control group, patients
      with high-does Atorvastatin taken, the risk of adverse cardiovascular events was
      degraded by 65% (Relative risk, RR=0.65, 95% confidence interval (CI): 0.50
      0.84), which was confirmed by trial sequential analysis as the cumulative Z curve
      entered the futility area. The subgroup analyses found that decreased risks of
      myocardial infarction among trails (RR=0.64, 95%CI: 0.50-0.83, RR=0.55, 95%CI:
      0.34-0.88). Egger and Begg's test found no publication bias (t=-1.670, P=0.129;
      Z=1.560, P=0.119). The use of high-dose Atorvastatin could reduce the risk of
      myocardial infraction and cardiovascular adverse events in patients with
      percutaneous coronary intervention. High-dose Atorvastatin was recommended as an
      adjunct to aid percutaneous coronary intervention.

PMID- 29050286
TI  - A prospective study of serum metabolites and glioma risk.
AB  - Malignant glioma is one of the most lethal adult cancers, yet its etiology
      remains largely unknown. We conducted a prospective serum metabolomic analysis of
      glioma based on 64 cases and 64 matched controls selected from Alpha-Tocopherol,
      Beta-Carotene Cancer Prevention (ATBC) Study. Median time from collection of
      baseline fasting serum to diagnosis was nine years (inter-decile range 3-20
      years). LC/MS-MS identified 730 known metabolites, and conditional logistic
      regression models estimated odds ratios for one-standard deviation differences in
      log-metabolite signals. Forty-three metabolites were associated with glioma at
      P<0.05. 2-Oxoarginine, cysteine, alpha-ketoglutarate, chenodeoxycholate and
      argininate yielded the strongest metabolite signals and were inversely related to
      overall glioma risk (0.0065<=P<0.0083). Also, seven xanthine metabolites related
      to caffeine metabolism were higher in cases than in controls (0.017<=P<0.042).
      Findings were mostly similar in high-grade glioma cases, although prominent
      inversely associated metabolites included the secondary bile acids glycocholenate
      sulfate and 3beta-hydroxy-5-cholenoic acid, xenobiotic methyl 4-hydroxybenzoate
      sulfate, sex steroid 5alpha-pregnan-3beta, 20beta-diol-monosulfate, and
      cofactor/vitamin oxalate (0.0091<=P<0.021). A serum metabolomic profile of glioma
      identified years in advance of clinical diagnoses is characterized by altered
      signals in arginine/proline, antioxidant, and coffee-related metabolites. The
      observed pattern provides new potential leads regarding the molecular basis
      relevant to etiologic or sub-clinical biomarkers for glioma.

PMID- 29050287
TI  - Association between the MVK and MMAB polymorphisms and serum lipid levels.
AB  - Maonan ethnic group is a relatively conservative and isolated minority in China.
      Little is known about the association of the mevalonate kinase (MVK),
      methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) single nucleotide
      polymorphisms (SNPs) and serum lipid levels. This study aimed to determine the
      association between four SNPs in the MVK/MMAB and serum lipid levels. Genotyping
      of the rs3759387, rs877710, rs7134594 and rs9593 SNPs was performed in 1264
      Maonan subjects and 1251 Han participants. Allele and genotype frequencies of the
      selected SNPs were different between the two populations (P < 0.05-0.001). Four
      SNPs were associated with high-density lipoprotein cholesterol (HDL-C) in the
      both ethnic groups (P < 0.0125-0.001); and one SNP with apolipoprotein (Apo) A1
      (rs7134594) in Han Chinese (P <0.0125). Strong linkage disequilibria were noted
      among the SNPs (D'=0.63-0.96; r2 =0.13-0.88). The commonest haplotype was C-C-C-T
      (> 50%). The frequencies of C-C-C-T, C-G-T-A, A-G-T-A, C-G-C-T, and A-C-T-A were
      different between the two populations (P <0.001). The associations between
      haplotypes and dyslipidemia were different in the Han and/or Maonan population (P
      < 0.05-0.001), haplotypes could explain much more serum lipid variation than any
      single SNP alone especially for HDL-C. Differences in lipid profiles between the
      two populations might partially attribute to these SNPs and their haplotypes.

PMID- 29050288
TI  - The protective effects of polysaccharide of Atractylodes macrocephala Koidz
      (PAMK) on the chicken spleen under heat stress via antagonizing apoptosis and
      restoring the immune function.
AB  - Heat stress can cause immune organ dysfunction and apoptosis. Polysaccharide of
      Atractylodes macrocephala Koidz may have protective effects on immune organs. In
      this study, we established chicken models of Polysaccharide of Atractylodes
      macrocephala Koidz-heat stress interaction and detected the oxidative index,
      activities of mitochondrial complexes and ATPases as well as the ultrastructure
      in chicken spleens. Expression levels of cytokines, mitochondrial dynamics- and
      apoptosis-related genes were also measured. In the result, heat stress increased
      the expression of interleukin 1 and tumour necrosis factor-alpha and decreased
      that of interleukin 2 and interferon gamma. The activities of mitochondrial
      complexes and ATPases were decreased and oxidative stress was induced by heat
      stress. Besides, expressions of the mitochondrial dynamics- and anti-apoptosis
      related genes were decreased and those of pro-apoptosis-related genes were
      increased by heat stress. HS induced pathological changes of mitochondria and
      triggered apoptosis in chicken spleens. However, these adverse effects triggered
      by HS were remarkably alleviated in Polysaccharide of Atractylodes macrocephala
      Koidz + heat stress group. This study confirmed the protective effects of
      Polysaccharide of Atractylodes macrocephala Koidz on the chicken spleen against
      the heat stress and revealed its mechanism, which is that Polysaccharide of
      Atractylodes macrocephala Koidz could relieve the heat stress-induced immune
      dysfunction of chicken spleens via reducing oxidative stress, enhancing the
      mitochondria function and inhibiting apoptosis.

PMID- 29050289
TI  - Acrolein induces mtDNA damages, mitochondrial fission and mitophagy in human lung
      cells.
AB  - Acrolein (Acr), a highly reactive unsaturated aldehyde, can cause various lung
      diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung
      cancer. We have found that Acr can damage not only genomic DNA but also DNA
      repair proteins causing repair dysfunction and enhancing cells' mutational
      susceptibility. While these effects may account for Acr lung carcinogenicity, the
      mechanisms by which Acr induces lung diseases other than cancer are unclear. In
      this study, we found that Acr induces damages in mitochondrial DNA (mtDNA),
      inhibits mitochondrial bioenergetics, and alters mtDNA copy number in human lung
      epithelial cells and fibroblasts. Furthermore, Acr induces mitochondrial fission
      which is followed by autophagy/ mitophagy and Acr-induced DNA damages can trigger
      apoptosis. However, the autophagy/ mitophagy process does not change the level of
      Acr-induced mtDNA damages and apoptosis. We propose that Acr-induced mtDNA
      damages trigger loss of mtDNA via mitochondrial fission and mitophagy. These
      processes and mitochondria dysfunction induced by Acr are causes that lead to
      lung diseases.

PMID- 29050290
TI  - GMI ablates cancer stemness and cisplatin resistance in oral carcinomas stem
      cells through IL-6/Stat3 signaling inhibition.
AB  - Cancer stem cells (CSCs) have been identified to exert tumor-initiating ability,
      resulting in the recurrence, metastasis and chemoresistance of oral squamous cell
      carcinomas. In the present study, we showed that GMI, an immunomodulatory protein
      from Ganoderma microsporum, induc ed a cytotoxic effect in oral carcinomas stem
      cells (OCSCs). Treatment of GMI dose-dependently inhibited the expression of CSC
      markers, including ALDH1 activity and CD44 positivity. Moreover, GMI suppressed
      the self-renewal property, colony formation, migration, and invasion abilities as
      well as potentiated chemo-sensitivity in OCSCs. Our results suggested that the
      tumor suppressive effect of GMI was mediated through inhibition of IL-6/Stat3
      signaling pathway. Furthermore, tumor growth was reduced in mice bearing
      xenograft tumors after oral administration of GMI. Taken together, we
      demonstrated the anti-CSC effect of GMI in oral cancer and GMI may serve as a
      natural cisplatin adjuvant to prevent cancer recurrence.

PMID- 29050291
TI  - Natural killer cell activity for IFN-gamma production as a supportive diagnostic
      marker for gastric cancer.
AB  - BACKGROUND/AIM: Decreased Natural killer cell activity (NKA) for interferon-gamma
      production (NKA-IFNgamma) has been reported in cancer patients. The aim of this
      study was to determine the diagnostic performance of NKA-IFNgamma for gastric
      cancer (GC). RESULTS: NKA-IFNgamma levels were decreased in 261 GC patients with
      all stages of tumor compared to those in 48 healthy donors (P < 0.001), and lower
      levels of NKA-IFNgamma were associated with higher GC stages. NKA-IFNgamma levels
      were also associated with clinicopathological parameters including tumor size,
      depth of invasion, and lymph node metastasis. NKA-INFgamma assay had better
      diagnostic value (AUC = 0.822) compared to serum CEA (0.624) or CA19-9 assay
      (0.566) (P < 0.001). Using different cut-off levels, serum CEA and CA19-9 showed
      sensitivities of 6.1-14.2% and 4.2-28.0%, respectively, which were much lower
      than that of NKA-IFNgamma (55.6-66.7%). METHODS: This study included 261 patients
      with newly diagnosed GC and 48 healthy donors. NKA for IFNgamma was determined by
      enzyme immunoassay after incubation of whole blood, and diagnostic performance
      was evaluated. CONCLUSIONS: NK cell activities for IFNgamma production could be
      used as a supportive non-invasive tumor marker for GC diagnosis.

PMID- 29050292
TI  - FOXK1 facilitates cell proliferation through regulating the expression of p21,
      and promotes metastasis in ovarian cancer.
AB  - Ovarian cancer is one of the most common cancer in the world. FOX family plays
      essential function in multiple cancers. In our work, FOXK1 was found to up
      regulate in ovarian cancer tissue samples and cell lines; moreover, the
      expression of FOXK1 was correlated with tumor size, metastasis and poorly
      prognosis. To evaluate the function of FOXK1 in ovarian cancer, we performed
      colony formation analysis, CCK-8 assay and cell cycle analysis to determine the
      effect of FOXK1 on cell proliferation and cell cycle. We found that FOXK1
      obviously improved the ability of cell proliferation through promoting cell
      cycle. Furthermore, ChIP assay and luciferase reporter assay indicated that FOXK1
      facilitated cell cycle through regulating the expression of p21, but FOXK1 had no
      effect on cell apoptosis. In addition, wound healing assay and transwell invasion
      analysis demonstrated that FOXK1 promoted migration and invasion in ovarian
      cancer. In conclusion, our work indicate FOXK1 plays a key function in the
      ovarian cancer, it promotes cell proliferation and metastasis. FOXK1 serves as a
      novel molecular therapy target in ovarian cancer.

PMID- 29050293
TI  - Proapoptotic function of deubiquitinase DUSP31 in Drosophila.
AB  - Drosophila have been used to identify new components in apoptosis regulation. The
      Drosophila protein Dark forms an octameric apoptosome complex that induces the
      initiator caspase Dronc to trigger the caspase cell death pathway and, therefore,
      plays an important role in controlling apoptosis. Caspases and Dark are
      constantly expressed in cells, but their activity is blocked by DIAP1 E3 ligase
      mediated ubiquitination and subsequent inactivation or proteasomal degradation.
      One of the regulatory mechanisms that stabilize proapoptotic factors is the
      removal of ubiquitin chains by deubiquitinases. In this study performed a
      modified genetic screen for deubiquitinases (dsRNA lines) to identify those
      involved in stabilizing proapoptotic components. Loss-of-function alleles of
      deubiquitinase DUSP31 were identified as suppressors of the Dronc overexpression
      phenotype. DUSP31 deficiency also suppresses apoptosis induced by the RHG
      protein, Grim. Genetic analysis revealed for the first time that DUSP31
      deficiency sufficiently suppresses the Dark phenotype, indicating its involvement
      in the control of Dark/Dronc apoptosome function in invertebrate apoptosis.

PMID- 29050294
TI  - The density of mast cells c-Kit+ and tryptase+ correlates with each other and
      with angiogenesis in pancreatic cancer patients.
AB  - Literature data suggest that inflammatory cells such as mast cells (MCs) are
      involved in angiogenesis. MCs can stimulate angiogenesis by releasing of well
      identified pro-angiogenic cytokines stored in their cytoplasm. In particular, MCs
      can release tryptase, a potent in vivo and in vitro pro-angiogenic factor.
      Nevertheless, few data are available concerning the role of MCs positive to
      tryptase in primary pancreatic cancer angiogenesis. This study analyzed the
      correlation between mast cells positive to c-Kit receptor (c-Kit+ MCs), the
      density of MCs expressing tryptase (MCD-T) and microvascular density (MVD) in
      primary tumor tissue from patients affected by pancreatic ductal adenocarcinoma
      (PDAC). A series of 35 PDAC patients with stage T2-3N0-1M0 (by AJCC for Pancreas
      Cancer Staging 7th Edition) were selected and then undergone to surgery. Tumor
      tissue samples were evaluated by mean of immunohistochemistry and image analysis
      methods in terms of number of c-Kit+ MCs, MCD-T and MVD. The above parameters
      were related each other and with the most important main clinico-pathological
      features. A significant correlation between c-Kit+ MCs, MCD-T and MVD groups each
      other was found by Pearson t-test analysis (r ranged from 0.75 to 0.87; p-value
      ranged from 0.01 to 0.04). No other significant correlation was found. Our in
      vivo preliminary data, suggest that tumor microenvironmental MCs evaluated in
      terms of c-Kit+ MCs and MCD-T may play a role in PDAC angiogenesis and they could
      be further evaluated as a novel tumor biomarker and as a target of anti
      angiogenic therapy.

PMID- 29050295
TI  - A comprehensive study of circulating tumour cells at the moment of prostate
      cancer diagnosis: biological and clinical implications of EGFR, AR and SNPs.
AB  - Circulating tumor cells (CTCs) have been recently accepted as prognostic markers
      in metastatic prostate cancer (PCa). However, very few studies have analyzed
      their role in early-stage PCa. The aim of this research is to study the value of
      CTCs at the moment of PCa diagnosis and to identify different subpopulations of
      CTCs. Patients with PSA value > 4 ng/ml and clinical suspicion of PCa were
      included. Samples were collected immediately before prostatic biopsy. CTCs were
      isolated by immunomagnetic technique using a multi-CK specific antibody.
      Molecular expression of EGFR and AR in the tissue was analysed by real-time PCR.
      Up to eight different SNPs in patients' blood DNA were studied. In a total of 86
      patients, the CTC detection rate was 18.6%. The sensitivity, specificity,
      positive and negative predictive values of CTCs to detect PCa was 14.2%, 78.4%,
      31.2% and 57.4%, respectively. Up to 75% of CTC-positive patients were AR
      negative. A direct association was found between the expression of AR in the
      prostatic tissue and the presence of CTCs in blood (p<0.05). We observed an
      inverse relation between the expression of EGFR in the tissue and the expression
      of AR in the CTCs. No significant association between SNPs and CTCs was found.
      The low detection rate of CTCs in early-stage PCa limits their role as a
      diagnostic marker. Nevertheless, we show that they may hide important prognostic
      information. Overexpression of AR in the prostate may facilitate cell
      dissemination.

PMID- 29050296
TI  - Reverse phase protein array identification of triple-negative breast cancer
      subtypes and comparison with mRNA molecular subtypes.
AB  - BACKGROUND: Reverse phase protein array (RPPA) analysis, allows investigation of
      potential targets at the functional protein level,. We identified TNBC subtypes
      at the protein level using RPPA and compared them with mRNA molecular subtypes
      (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA
      and mRNA analyses. METHODS: We classified the samples from 80 TNBC patients using
      both k-means and hierarchical consensus clustering analysis and performed
      Ingenuity Pathway Analysis. We also investigated whether we could reproduce the
      mRNA molecular subtypes using the RPPA dataset. RESULTS: Both clustering methods
      divided all samples into 2 clusters that were biologically the same. The top
      canonical pathways included inflammation, hormonal receptors, and MAPK signaling
      pathways for the first cluster ["inflammation and hormonal-related (I/H)
      subtype"] and the GADD45, DNA damage, and p53 signaling pathways for the second
      cluster ["DNA damage (DD)-related subtype"]. Further k-means cluster analysis
      identified 5 TNBC clusters. Comparison between sample classification using the 5
      RPPA-based k-means cluster subtypes and 6 gene-expression-based TNBCtype
      molecular subtypes showed significant association between the 2 classifications
      (p = 0.017). CONCLUSIONS: The I/H and DD subtypes identified by RPPA advance our
      understanding of TNBC's heterogeneity from the functional proteomic perspective.

PMID- 29050297
TI  - Cytochalasin B-induced membrane vesicles convey angiogenic activity of parental
      cells.
AB  - Naturally occurring extracellular vesicles (EVs) play essential roles in
      intracellular communication and delivery of bioactive molecules. Therefore it has
      been suggested that EVs could be used for delivery of therapeutics. However, to
      date the therapeutic application of EVs has been limited by number of factors,
      including limited yield and full understanding of their biological activities. To
      address these issues, we analyzed the morphology, molecular composition, fusion
      capacity and biological activity of Cytochalasin B-induced membrane vesicles
      (CIMVs). The size of these vesicles was comparable to that of naturally occurring
      EVs. In addition, we have shown that CIMVs from human SH-SY5Y cells contain
      elevated levels of VEGF as compared to the parental cells, and stimulate
      angiogenesis in vitro and in vivo.

PMID- 29050298
TI  - Overexpression of COL3A1 confers a poor prognosis in human bladder cancer
      identified by co-expression analysis.
AB  - Human bladder cancer (BCa) is one of the worldwide cancers in men and women
      populations, with the etiology and mechanism unknown. In our study, we
      constructed a weighted gene co-expression network to identify gene modules
      associated with the progression of BCa (n = 93). In the significant module (R2 =
      0.48), a total of 103 network hub genes were identified, and 4 of them were hub
      nodes in the protein-protein interaction network as well. In validation, COL3A1
      showed a higher correlation with the disease progression than any other hub genes
      in hub module in the test set (p < 0.001). Functional and pathway enrichment
      analysis demonstrated that COL3A1 is overrepresented in pathway of focal
      adhesion, which associated with tumor progression and might cause metastasis.
      Gene set enrichment analysis (GSEA) also demonstrated that the gene set of "MAPK
      signaling pathway" and focal adhesion related pathways were enriched in BCa
      samples with COL3A1 highly expressed (FDR < 0.05). Considering the
      clinicopathological parameters, highly-expressed COL3A1 was closely correlated
      with local recurrence and BCa stage. Survival analysis revealed that BCa patients
      with higher expression of COL3A1 had a significantly shorter overall survival
      time and disease free survival time.In conclusion, based on the co-expression
      analysis, COL3A1 was identified in the association with progression and prognosis
      of BCa, which might refer a poor prognosisprobably by regulating MAPK signaling
      pathway.

PMID- 29050299
TI  - Exostosin 1 regulates cancer cell stemness in doxorubicin-resistant breast cancer
      cells.
AB  - Cancer stem cells (CSCs) are associated with cancer recurrence following
      radio/chemotherapy owing to their high resistance to therapeutic intervention. In
      this study, we investigated the role of exostoxin 1 (EXT1), an endoplasmic
      reticulum (ER)-residing type II transmembrane glycoprotein, in cancer cell
      stemness. DNA microarray analysis revealed that doxorubicin-resistant MCF7/ADR
      cells have high levels of EXT1 expression compared to its parental cell line,
      MCF7. These cells showed significantly higher populations of CSCs and larger
      populations of aldehyde dehydrogenase (ALDH+) and CD44+/CD24-cells, as compared
      to MCF7 cells. siRNA-mediated knockdown of EXT1 in MCF7/ADR cells significantly
      reduced cancer stem cell markers, populations of ALDH+and CD44+/CD24- cells, mRNA
      and protein expression for CD44, and mammosphere number. Furthermore, epithelial
      mesenchymal transition (EMT) markers and migratory behavior were also repressed
      with reduced EXT1. In an in vitro soft agar colony formation assay, EXT1
      knockdown by short hairpin RNA (shRNA) reduced the colony formation ability of
      these cells. Based on these results, we suggest that EXT1 could be a promising
      novel target to overcome cancer cell stemness in anthracycline-based therapeutic
      resistance.

PMID- 29050300
TI  - TFCP2 activates beta-catenin/TCF signaling in the progression of pancreatic
      cancer.
AB  - Aberrant activation of beta-catenin/TCF (T-cell factor) signaling is frequently
      observed in the pancreatic cancer. However, the regulation of nuclear beta
      catenin/TCF transcription machinery remains largely unknown. In this study, TFCP2
      (transcriptional factor CP2) expression in pancreatic cancer was detected by
      qPCR, immunohistochemistry and western blot. Western blot, colony formation
      assay, migration and invasion experiment were performed to investigate the
      effects of TFCP2 on the growth and migration of pancreatic cancer cells. In vivo,
      mouse metastasis models were utilized to determine metastasis ability. Western
      blots were used to evaluate the related protein expression. Luciferase reporter
      assay was used to explore the role of TFCP2 on beta-catenin/TCF signaling. We
      have shown that the transcription factor TFCP2 was up-regulated in the pancreatic
      cancer. Over-expression of TFCP2 promoted the growth, migration, invasion and
      colony formation of pancreatic cancer cells, while knocking down the expression
      of TFCP2 inhibited the growth, migration, invasion, colony formation and
      metastasis of pancreatic cancer cells. The mechanism study revealed that TFCP2
      interacted beta-catenin, enhanced the interaction between beta-catenin and TCF4,
      and activated beta-catenin/TCF signaling. Taken together, our study demonstrated
      the oncogenic roles of TFCP2 in pancreatic cancer, and suggested that TFCP2 might
      be a target for the treatment of pancreatic cancer.

PMID- 29050301
TI  - MiR-377 promotes white adipose tissue inflammation and decreases insulin
      sensitivity in obesity via suppression of sirtuin-1 (SIRT1).
AB  - Obesity is associated with a wide range of metabolic disorders including
      inflammation and insulin-resistance. Sirtuin-1 (SIRT1) is an important regulator
      of metabolic homeostasis and stress response pathways in white adipose tissue.
      However, involvement of microRNAs (miRNAs) in regulating SIRT1 during obesity
      induced inflammation and insulin-resistance remains unclear. Here, we found that
      miR-377 was upregulated in adipose tissue and showed a negative correlation with
      SIRT1 in chronic high fat diet (HFD)-fed mice. MiR-377 belongs to a large miRNA
      cluster and functions as an important tumor suppressor in several human
      malignancies. Recently, it has also gained considerable attention in oxidative
      stress and diabetic nephropathy. In our present study, we found that
      overexpression of miR-377 decreased SIRT1 protein abundance and caused
      inflammation and insulin-resistance in differentiated 3T3-L1 cells. Conversely,
      miR-377 inhibition increased SIRT1 mRNA and protein levels, ameliorated
      inflammation and improved insulin sensitivity. Furthermore, we demonstrated that
      miR-377 targets the 3'-UTR of SIRT1 mRNA directly, and downregulates SIRT1
      protein abundance. Inhibition of SIRT1 by EX527 significantly eliminated the
      downregulation of the inflammation and insulin-resistance levels induced by the
      miR-377 inhibitor. Furthermore, SIRT1 deficiency intensified adipose tissue
      inflammation and insulin-resistance, resulting in hepatic steatosis in chronic
      HFD-fed mice. In conclusion, our findings suggest that miR-377 promotes white
      adipose tissue inflammation and decreases insulin sensitivity in obesity, at
      least in part, through suppressing SIRT1.

PMID- 29050302
TI  - 2L-PCA: a two-level principal component analyzer for quantitative drug design and
      its applications.
AB  - A two-level principal component predictor (2L-PCA) was proposed based on the
      principal component analysis (PCA) approach. It can be used to quantitatively
      analyze various compounds and peptides about their functions or potentials to
      become useful drugs. One level is for dealing with the physicochemical properties
      of drug molecules, while the other level is for dealing with their structural
      fragments. The predictor has the self-learning and feedback features to
      automatically improve its accuracy. It is anticipated that 2L-PCA will become a
      very useful tool for timely providing various useful clues during the process of
      drug development.

PMID- 29050303
TI  - Dysregulated expression of homeobox family genes may influence survival outcomes
      of patients with epithelial ovarian cancer: analysis of data from The Cancer
      Genome Atlas.
AB  - Homeobox (HOX) family genes encode key transcription factors for embryogenesis
      and may be correlated with carcinogenesis. The aim of this study was to elucidate
      whether aberrant expression of HOX genes influences outcomes in epithelial
      ovarian cancer (EOC). Gene expression data and clinicopathologic information from
      630 patients with EOC were downloaded from The Cancer Genome Atlas database. We
      explored correlations between expression levels of HOX gene family members and
      clinicopathological variables. Higher expression of HOXA1, A4, A5, A7, A10, A11,
      B13, C13, D1, and D3 was associated with advanced FIGO stage. Suboptimal residual
      disease after debulking surgery was significantly correlated with higher
      expression of HOXB9, B13, and C13. Additionally, patients with high expression of
      HOXC6 and C11 were significantly more likely to have poor performance status.
      Overall survival was significantly shorter in patients with high, rather than
      low, expression of two HOX genes (HOXA10 and B3), and significantly longer in
      patients with high rather than low HOXC5 expression. Dysregulated expression of
      the HOXA10, B3, and C5 was significantly correlated with overall survival in EOC
      patients. HOX gene expression levels are potentially useful as a prognostic
      indicator in EOC, and HOX genes may represent a novel and promising target for
      anticancer therapeutics.

PMID- 29050304
TI  - Validation of the 8th edition of the UICC/AJCC staging system for nasopharyngeal
      carcinoma treated with intensity-modulated radiotherapy.
AB  - An accurate TNM staging system is crucial for treatment guidance and prognosis
      prediction in nasopharyngeal carcinoma (NPC) patients. In this retrospective
      study, we evaluated the 8th edition of the Union for International Cancer
      Control/American Joint Committee on Cancer (UICC/AJCC) staging system for NPC
      treated with intensity-modulated radiotherapy (IMRT). A total of 608 patients
      with biopsy-proven, non-metastatic NPC, treated with IMRT between January 2008
      and March 2010, were enrolled. The 5-year overall survival (OS), disease-free
      survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free
      survival (DMFS) rates were 81.5%, 80.1%, 86.0%, and 81.1%, respectively. The LRFS
      rates of patients with stages T1 vs. T2, T2 vs. T3, and T1 vs. T3 did not differ
      between the 7th and 8th editions. By contrast, the DMFS rates of patients with N0
      vs. N1, N1 vs. N2, and N2 vs. N3 differed between the 8th and the 7th editions,
      though no difference was observed between N3a and N3b, according to the 7th
      edition. The difference in OS between stages II and III, and between stages III
      and IVa, was larger according to the 8th edition than the 7th edition. There was
      no difference in the OS between stages I and II. These data indicate that in the
      IMRT era, the 8th edition staging system can predict the prognosis of NPC
      patients more accurately than the 7th edition.

PMID- 29050305
TI  - Calyxin Y sensitizes cisplatin-sensitive and resistant hepatocellular carcinoma
      cells to cisplatin through apoptotic and autophagic cell death via SCF betaTrCP
      mediated eEF2K degradation.
AB  - The down-regulation of eukaryotic elongation factor-2 kinase (eEF2K) is
      associated with an enhancement in the sensitivity of malignant cells to
      chemotherapeutic agents. In this study, we found that the silencing of eEF2K
      enhanced cisplatin (CDDP)-induced cytotoxicity in CDDP-sensitive (HepG2) and
      resistant (HepG2/CDDP) cells. Calyxin Y, a unique chalcone diarylheptanoid
      adduct, down-regulated eEF2K by promoting Skp1-Cul1-F-box protein (SCF) beta
      transducin repeat-containing protein (betaTrCP)-mediated protein degradation and
      synergistically enhanced the cytotoxicity of CDDP. Subsequently, we identified a
      potential mechanism of this cooperative interaction by showing that the
      combination of calyxin Y and CDDP enhanced apoptotic cell death via mitochondrial
      dysfunction. In addition, the combination induced autophagy, which contributed to
      the synergistic cytotoxic effect. Further research revealed that calyxin Y
      synergistically sensitized HepG2 and HepG2/CDDP cells to CDDP through enhanced
      apoptotic and autophagic cell death via the SCF betaTrCP-eEF2K pathway. Finally,
      in vivo studies demonstrated that calyxin Y could enhance the response of
      HepG2/CDDP cells to CDDP in xenograft models with low systemic toxicity. Thus,
      the combination of calyxin Y and CDDP might represent an attractive therapeutic
      strategy for the treatment of chemotherapy-sensitive and resistant hepatocellular
      carcinoma cells.

PMID- 29050306
TI  - The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and
      dissemination of colorectal cancer.
AB  - In colorectal cancer (CRC), RHAMM is an independent adverse prognostic factor.
      The aim of the study was therefore to investigate on the role of RHAMM as a
      potential direct driver of cell proliferation and migration in CRC cell lines and
      to identify pathways dependent on RHAMM in human CRC. Proliferation, cell cycle
      alterations and invasive capacity were tested in two RHAMM- and control-
      knockdown CRC cell lines by flow cytometry and in vitro assays. Tumorigenicity
      and metastasis formation was assessed in immunodeficient mice. RNA-Seq and
      immunohistochemistry was performed on six RHAMM+/- primary CRC tumors. In vitro,
      silencing of RHAMM inhibited CRC cell migration and invasion by 50% (p<0.01). In
      vivo, RHAMM knockdown resulted in slower growth, lower tumor size (p<0.001) and
      inhibition of metastasis (p<0.001). Patients with RHAMM-high CRC had a worse
      prognosis (p=0.040) and upregulated pathways for cell cycle progression and
      adhesion turnover. RHAMM overexpression is correlated with increased migration
      and invasion of CRC cells, leads to larger, fast growing tumors, and its
      downregulation essentially abolishes metastasis in mouse models. RHAMM is
      therefore a promising therapeutic target in all CRC stages as its inhibition
      affects growth and dissemination of the primary CRC as well as the metastases.

PMID- 29050307
TI  - LncSHRG promotes hepatocellular carcinoma progression by activating HES6.
AB  - Hepatocellular carcinoma, one of the most common cancers, leads to mass mortality
      worldwide currently. However, the underlying mechanism of its oncogenesis remains
      to be elucidated. Here we identified that a long noncoding RNA, lncSHRG, was
      greatly upregulated in human hepatocellular carcinoma samples. We found that
      lncSHRG was essential for liver cancer cell proliferation and tumor propagation
      in mice. In mechanism, lncSHRG recruits SATB1 to bind to HES6 promoter and
      initiates HES6 expression. HES6, which is highly expressed in hepatocellular
      carcinoma, promotes tumor cell proliferation. High expression level of HES6 is
      positively correlated with clinical severity and poor prognosis of people with
      hepatocellular carcinoma. Altogether, our research provides a new insight on the
      mechanism of hepatocellular carcinoma progression.

PMID- 29050308
TI  - The lncRNA HOXA11-AS functions as a competing endogenous RNA to regulate PADI2
      expression by sponging miR-125a-5p in liver metastasis of colorectal cancer.
AB  - Several long non-coding RNAs (lncRNAs) play important roles in the regulation of
      liver metastasis in colorectal cancer (CRC) patients. We previously described the
      potential involvement of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS), miR
      125a-5p, and peptidyl arginine deiminase 2 (PADI2) in promoting liver metastasis
      in CRC patients. In the present study, we verified the significant upregulation
      of HOXA11-AS and PADI2, as well as the downregulation of miR-125a-5p, in CRC
      patients with liver metastasis. Overexpression and knockdown studies of HOXA11-AS
      or PADI2, as well as gain-/loss-of-function studies of miR-125a-5p, revealed a
      positive correlation between HOXA11-AS and PADI2 and a negative correlation with
      miR-125a-5p in the regulation of liver metastasis in CRC cell lines. Overall, we
      conclude that HOXA11-AS promotes liver metastasis in CRC by functioning as a miR
      125a-5p sponge and describe a novel HOXA11-AS-miR-125a-5p-PADI2 regulatory
      network involved in CRC liver metastasis.

PMID- 29050309
TI  - Fibronectin in cell adhesion and migration via N-glycosylation.
AB  - Directed cell migration is an important step in effective wound healing and
      requires the dynamic control of the formation of cell-extracellular matrix
      interactions. Plasma fibronectin is an extracellular matrix glycoprotein present
      in blood plasma that plays crucial roles in modulating cellular adhesion and
      migration and thereby helping to mediate all steps of wound healing. In order to
      seek safe sources of plasma fibronectin for its practical use in wound dressing,
      we isolated fibronectin from human (homo) and porcine plasma and demonstrated
      that both have a similar ability as a suitable substrate for the stimulation of
      cell adhesion and for directing cell migration. In addition, we also defined the
      N-glycosylation sites and N-glycans present on homo and porcine plasma
      fibronectin. These N-glycosylation modifications of the plasma fibronectin
      synergistically support the integrin-mediated signals to bring about mediating
      cellular adhesion and directed cell migration. This study not only determines the
      important function of N-glycans in both homo and porcine plasma fibronectin
      mediated cell adhesion and directed cell migration, but also reveals the
      potential applications of porcine plasma fibronectin if it was applied as a
      material for clinical wound healing and tissue repair.

PMID- 29050310
TI  - MicroRNA-27b inhibition promotes Nrf2/ARE pathway activation and alleviates
      intracerebral hemorrhage-induced brain injury.
AB  - Oxidative stress and neuroinflammation are the key factors leading to secondary
      brain injury after intracerebral hemorrhage (ICH). We investigated the effects of
      miR-27b, an oxidative stress-responsive microRNA, on ICH-induced brain injury in
      rats. The ICH model was induced by intracerebral injection of collagenase.
      Following ICH, miR-27b expression in the striatum was reduced, whereas expression
      of Nrf2 mRNA and protein was increased. In PC12 cells, overexpression of miR-27b
      reduced expression of Nrf2, Hmox1, Sod1 and Nqo1, while miR-27b inhibition had
      the opposite effects. Dual luciferase reporter assays showed that Nrf2 mRNA was a
      direct target of miR-27b. Intracerebroventricular injection of miR-27b antagomir
      and transfection of miR-27b inhibitor inhibited endogenous miR-27b in rats and
      PC12 cells, respectively. MiR-27b antagomir promoted activation of the ICH
      induced Nrf2/ARE pathway and reduced the lipid peroxidation, neuroinflammation,
      cell death and neurological deficits otherwise seen after ICH. In PC12 cells, the
      miR-27b inhibitor diminished iron-induced oxidative stress, inflammation and
      apoptosis, and those effects were blocked by Nrf2 knockdown. These results
      demonstrate that miR-27b inhibition alleviates ICH-induced brain injury, which
      may be explained in part by its regulation on the Nrf2/ARE pathway.

PMID- 29050311
TI  - TMEM17 depresses invasion and metastasis in lung cancer cells via ERK signaling
      pathway.
AB  - Transmembrane protein 17(TMEM17) is a newly identified protein, its expression
      pattern and clinicopathological relevance is still unclear. In this study,
      western blot assay was performed in 20 paired lung cancer samples and found that
      TMEM17 protein levels were lower in lung cancer tissues than that in the
      corresponding normal lung tissues (p=0.010). Immunohistochemistry staining in 143
      cases lung cancer specimens also showed that TMEM17 expression in lung cancer
      tissues were significantly lower than adjacent normal lung tissues (35.7% vs
      63.2%, p<0.001). And negative TMEM17 expression was significantly associated with
      poor histological differentiation (p=0.027), advanced TNM stages (p=0.006),
      positive lymph node metastasis (p=0.002) and poor prognosis (p=0.002). After
      overexpressing TMEM17, levels of p-ERK and its downstream molecules, p-P90RSK and
      Snail, were down-regulated, while levels of Occludin and Zo-1 were up-regulated,
      which result in the inhibition of invasion and migration ability of lung cancer
      cells. The effects were reversed by the incorporation of specific ERK inhibitor
      PD98059. In conclusion, loss of TMEM17 correlates with the development of non
      small cell lung cancer (NSCLC) and predicts adverse clinical outcome of NSCLC
      patients. The effect of TMEM17 on inhibiting invasion and migration may attribute
      to restoring Occludin and Zo-1 expression through inactivating ERK-P90RSK-Snail
      pathway.

PMID- 29050312
TI  - Non-alcoholic steatohepatitis-related liver tumorigenesis is suppressed in mice
      lacking hepatic retinoid storage.
AB  - Non-alcoholic fatty liver disease has become one of the most common causes of
      chronic liver disease that can develop into a more serious form, non-alcoholic
      steatohepatitis, leading to liver cirrhosis and hepatocellular carcinoma.
      Although hepatic retinoid stores are progressively lost during the development of
      liver disease, how this affects steatohepatitis and its related
      hepatocarcinogenesis is unknown. In order to investigate these, we used
      subcutaneous injection of streptozotocin (0.2 mg/body) and high-fat diet to
      induce steatohepatitis and hepatic tumorigenesis in lecithin:retinol
      acyltransferase -deficient mice (n = 10), which lack stored retinoid in the
      liver, and control mice (n = 12). At the termination of the experiment (16 weeks
      of age), the development of hepatic tumors was significantly suppressed in mutant
      mice compared to controls. Lower serum levels of alanine aminotransferase and
      decreased hepatic levels of cyclin D1 were observed in mutant mice. Mutant mice
      exhibited increased levels of retinoic acid-responsive genes, including p21, and
      decreased oxidative stress as evaluated by serum and liver markers. Our findings
      are consistent with the conclusion that mutant mice are less susceptible to
      steatohepatitis-related liver tumorigenesis due to increased retinoid signaling,
      which is accompanied by up-regulated p21 expression and attenuated oxidative
      stress.

PMID- 29050313
TI  - Adipose-derived mesenchymal stem cells employed exosomes to attenuate AKI-CKD
      transition through tubular epithelial cell dependent Sox9 activation.
AB  - Acute kidney injury (AKI) predisposes patients to an increased risk into
      progressive chronic kidney disease (CKD), however effective treatments are still
      elusive. This study aimed to investigate the therapeutic efficacy of human
      adipose-derived MSCs (hAD-MSCs) in the prevention of AKI-CKD transition, and
      illuminate the role of Sox9, a vital transcription factor in the development of
      kidney, in this process. C57BL/6 mice were subjected to unilateral renal
      ischemia/reperfusion (I/R) with or without hAD-MSC treatment. We found that hAD
      MSC treatment upregulated the expression of tubular Sox9, promoted tubular
      regeneration, attenuated AKI, and mitigated subsequent renal fibrosis. However,
      these beneficial effects were abolished by a drug inhibiting the release of
      exosomes from hAD-MSCs. Similarly, Sox9 inhibitors reversed these protective
      effects. Further, we verified that hAD-MSCs activated tubular Sox9 and prevented
      TGF-beta1-induced transformation of TECs into pro-fibrotic phenotype through
      exosome shuttling in vitro, but the cells did not inhibit TGF-beta1-induced
      transition of fibroblasts into myofibroblasts. Inhibiting the release of exosomes
      from hAD-MSCs or the expression of Sox9 in TECs reversed these antifibrotic
      effects. In conclusion, hAD-MSCs employed exosomes to mitigate AKI-CKD transition
      through tubular epithelial cell dependent activation of Sox9.

PMID- 29050314
TI  - Applicability of graded prognostic assessment of lung cancer using molecular
      markers to lung adenocarcinoma patients with brain metastases.
AB  - Several scoring systems are available to estimate prognosis and assist in
      selecting treatment methods for non-small cell lung cancer (NSCLC) patients with
      brain metastasis, including recursive partitioning analysis (RPA), basic score
      for brain metastases (BS-BM), and diagnosis-specific graded prognostic assessment
      (DS-GPA). Lung-molGPA is an update of the DS-GPA that incorporates EGFR and/or
      ALK mutation status. The present study tested the applicability of these four
      indexes in 361 lung adenocarcinoma patients with brain metastasis. Potential
      predictive factors in our independent multivariate analysis included patient age,
      Karnofsky performance status, EGFR and ALK mutation status, and use of targeted
      therapy. In the log-rank test, all four systems predicted overall survival (OS)
      (P<0.001). Harrell's C indexes were 0.732, 0.724, 0.729, and 0.747 for RPA, BS
      BM, DS-GPA, and Lung-molGPA, respectively. Our results confirmed that the Lung
      molGPA index was useful for estimating OS in our patient cohort, and appeared to
      provide the most accurate predictions. However, the independent prognostic
      factors identified in our study were not entirely in agreement with the Lung
      molGPA factors. In an era of targeted therapy, Lung-molGPA must be further
      updated to incorporate more specific prognostic factors based on additional
      patient data.

PMID- 29050315
TI  - The activation of SRC family kinases and focal adhesion kinase with the loss of
      the amplified, mutated EGFR gene contributes to the resistance to afatinib,
      erlotinib and osimertinib in human lung cancer cells.
AB  - Second- and third-generation inhibitors of epidermal growth factor receptor
      (EGFR) tyrosine kinase activity (EGFR-TKIs) are improving the treatment of
      patients with non-small cell lung cancer. Here we established two sublines (BR1-8
      and BR2-3) resistant to a second-generation inhibitor, afatinib, from the human
      lung cancer cell line HCC827 that harbors a mutation that activates the tyrosine
      kinase activity of EGFR. These afatinib-resistant sublines were resistant to
      first-generation EGFR-TKIs, gefitinib and erlotinib, and a third-generation EGFR
      TKI, osimertinib. These resistant sublines showed markedly reduced levels of
      multiple EGFR family proteins, including the activated mutant EGFR, and complete
      loss of EGFR amplification as compared with their parental HCC827 cells harboring
      amplification of EGFR gene. Treatment with the multikinase inhibitor dasatinib or
      transfection with a SRC small interfering RNA inhibited cell survival and AKT
      phosphorylation in drug-resistant sublines to a greater extent compared with
      HCC827 cells. Further, the migration of drug-resistant cells was greater compared
      with that of HCC827 cells and was inhibited by dasatinib or an FAK inhibitor.
      These findings indicate that compensatory activation of SRC family kinases (SFKs)
      and FAK supports the survival and migration of afatinib-resistant cells when the
      expression of multiple EGFR family proteins was mostly abrogated. Combinations of
      potent drugs that target SFKs and FAK may overcome the resistance of lung cancer
      cells to second-generation TKIs.

PMID- 29050316
TI  - Pharmacokinetics and drug-drug interaction between enalapril, enalaprilat and
      felodipine extended release (ER) in healthy subjects.
AB  - Since angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have
      complimentary mechanisms of action, enalapril, an ACE inhibitor, is used in
      combination with felodipine, a vascular selective dihydropyridine calcium
      antagonist, for the treatment of hypertension. The present study was designed to
      investigate the possible drug-drug interaction between these two agents in
      Chinese healthy subjects. A randomized, open-label, multiple-dose, 3-treatment, 3
      period, 6-sequence cross-over study enrolling 12 healthy subjects (six male and
      six female subjects) was performed. Plasma pharmacokinetic studies were performed
      after 5 mg of enalapril and 5 mg of felodipine were administered alone or
      concomitantly twice per day for six days, and once in the morning of day seven.
      All 12 healthy subjects (mean [SD] age, 24.3 [2.8] years; body weight, 57.3 [5.7]
      kg; height, 163.2 [5.2] cm) completed all scheduled pharmacokinetic studies.
      Geometric mean ratios (with 90% CIs) of AUCtau,ss and Cmax,ss for enalapril
      administered concomitantly with felodipine vs. enalapril administered alone were
      1.025 (0.80-1.25) and 1.065 (0.70-1.43), respectively. Geometric mean ratios
      (with 90% CIs) of AUCtau,ss and Cmax,ss for felodipine administered concomitantly
      with enalapril vs. felodipine administered alone were 1.14 (0.97-1.31) and 0.80
      (0.65-0.95), respectively. There were no severe or serious drug-related adverse
      events observed during the study. Our results revealed that the co-administration
      of enalapril and felodipine affected the pharmacokinetics of felodipine, but not
      that of enalapril. Although the difference in PK parameters was statistically
      significant, its clinical significance may be limited, considering safety profile
      observed in the present study.

PMID- 29050317
TI  - MicroRNA-542-3p inhibits oral squamous cell carcinoma progression by inhibiting
      ILK/TGF-beta1/Smad2/3 signaling.
AB  - In this study, we investigated the effects of microRNA-542-3p (miR-542-3p) on
      ILK/TGF-beta1/Smad2/3 signaling and oral squamous cell carcinoma (OSCC)
      progression. Levels of miR-542-3p were lower in OSCC tissues (n=108) than
      adjacent normal tissues, whereas levels of ILK, TGF-beta1 and Smad2/3 were
      higher. Patients with undifferentiated tumors, advanced TNM stage and lymph node
      metastasis showed low miR-542-3p levels. This was accompanied by high ILK
      expression and poor survival. Dual luciferase reporter assays of SCC-9 cells
      showed that miR-542-3p inhibited ILK gene expression by binding to its 3'UTR at
      233-240 bp. SCC-9 cells transfected with miR-542-3p mimics exhibited elevated miR
      542-3p and decreased ILK, TGF-beta1 and Smad2/3 expression. They also showed
      reduced self-renewal (fewer CD44+ cells and tumor-spheres), invasiveness,
      migration, proliferation and survival. Conversely, miR-542-3p inhibitors promoted
      increased self-renewal (more CD44+ cells and tumor-spheres), invasiveness,
      migration, proliferation and survival. In xenograft experiments with nude mice,
      SCC-9 cells transfected with miR-542-3p mimics or siRNA-ILK yielded tumors with
      smaller volumes and weights than control tumors. These results demonstrate that
      miR-542-3p is a tumor suppressor that inhibits ILK/TGF-beta1/Smad2/3 signaling,
      thereby inhibiting OSCC progression.

PMID- 29050318
TI  - Unanticipated prognosis of differential thyroid cancer patients with T0 stage:
      analysis of the SEER database 2004-2013.
AB  - The prognosis of T0 stage differentiated thyroid cancer (DTC) remains unclear.
      This study aimed to investigate the prognosis of T0 stage DTC patients to provide
      a new perspective on treatment guidelines for these patients. We investigated a
      large cohort of DTC patients from the Surveillance, Epidemiology, and End Results
      (SEER) database between 2004 and 2013. Patient survival curves were examined by
      Kaplan-Meier analyses with log-rank tests and Cox proportional hazards regression
      analyses. In the study cohort, the rate of cancer-specific mortality per 1000
      person-years for T0 was higher than T1-T3, but lower than T4. The all-cause
      mortality for T0 patients was higher than all other stages (T1-T4). Multivariate
      Cox regression modeling showed that T0 had a significant risk for cancer-specific
      mortality when compared to T1 and T4, but not T2 or T3, after adjustment for
      other risk factors. For all-cause mortality, T0 showed a significant risk for all
      cause mortality when compared to T4, but not T1-T3 stage patients. Similar
      results were obtained after matching for influential factors using propensity
      scored matching analysis. The unanticipated prognosis of T0 stage DTC patients
      was found to be not better than of other stage DTC patients, providing new
      implications for the treatment of T0 stage DTC patients.

PMID- 29050319
TI  - Clinical efficacy of endostar combined with chemotherapy in the treatment of
      peritoneal carcinomatosis in gastric cancer: results from a retrospective study.
AB  - Peritoneal carcinomatosis (PC) resulting from metastatic dissemination of gastric
      cancer (GC) cells carries a dismal prognosis, and current treatments have shown
      little efficacy. This study aimed to evaluate the efficacy and safety of
      recombinant human endostatin (Endostar), a broad-spectrum anti-angiogenic
      peptide, in combination with chemotherapy in PC derived from GC. From January
      2014 to December 2016, 33 patients with advanced stage GC associated with PC were
      enrolled. Pathological, imaging, and treatment data were retrospectively
      analyzed. Twenty-one patients received systemic chemotherapy (control group),
      while 12 patients were administered Endostar and chemotherapy. Combined treatment
      with Endostar/chemotherapy showed the tendency to increase objective response
      rate (41.7% vs. 23.8%) and disease control rate (83.3% vs. 61.9%) compared with
      the control group, although the differences were not statistically significant.
      Endostar plus chemotherapy effectively extended time to progression (4.6 +/- 0.3
      months vs. 3.5 +/- 0.3 months, P = 0.03) and median overall survival (15.8 +/-
      1.7 months vs. 9.8 +/- 0.9 months, P = 0.01) compared with chemotherapy alone.
      The combination therapy did not cause more adverse reactions than chemotherapy
      alone. Thus, the addition of Endostar to conventional chemotherapy treatment
      effectively attenuated the development of PC and extended survival, with high
      safety and tolerance.

PMID- 29050320
TI  - Epigenetic regulation of interleukin-8 expression by class I HDAC and CBP in
      ovarian cancer cells.
AB  - Although inhibitors of epigenetic regulators have been effective in the treatment
      of cutaneous T cell lymphoma (CTCL) and other hematopoietic malignancies, they
      have been less effective in solid tumors, including ovarian cancer (OC). We have
      previously shown that inhibition of histone deacetylase (HDAC) activity induces
      expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8
      (CXCL8, IL-8) in OC cells, resulting in their increased survival and
      proliferation. Here, we show that in addition to ovarian cancer SKOV3, OVCAR3,
      and CAOV3 cells, HDAC inhibition induces the CXCL8 expression in HeLa cells, but
      not in CTCL Hut-78 cells. In OC cells, the CXCL8 expression is induced by
      pharmacological inhibition of class I HDACs. Interestingly, while an individual
      suppression of HDAC1, HDAC2, or HDAC3 by corresponding siRNAs inhibits the CXCL8
      expression, their simultaneous suppression induces the CXCL8 expression. The
      induced CXCL8 expression in OC cells is dependent on histone acetyltransferase
      (HAT) activity of CREB-binding protein (CBP), but not p300, and is associated
      with HAT-dependent p65 recruitment to CXCL8 promoter. Together, our results show
      that the CXCL8 expression in OC cells is induced by combined inhibition of HDAC1,
      -2, and -3, and silenced by suppression of HAT activity of CBP. In addition, our
      data indicate that the induced CXCL8 expression may be responsible for the
      limited effectiveness of HDAC inhibitors in OC and perhaps other solid cancers
      characterized by CXCL8 overexpression, and suggest that targeting class I HDACs
      and CBP may provide novel combination strategies by limiting the induced CXCL8
      expression.

PMID- 29050321
TI  - Interaction among CYP2C8, GPIIIa and P2Y12 variants increase susceptibility to
      ischemic stroke in Chinese population.
AB  - PURPOSE: Genetic variants in cytochrome P450 (CYP), platelet membrane receptor
      (P2Y12, P2Y1), and glycoprotein IIIa (GPIIIa) genes are associated with the
      efficacy of clopidogrel and adverse clinical events on ischemic stroke (IS)
      patients. However, few studies have assessed whether gene-gene interactions among
      these genes influence the risk of IS. The aim of the present study was to
      investigate the association of fifteen variants with IS and to determine whether
      these gene-gene interactions increase the risk of IS. METHODS: Fifteen variants
      in CYP3A4, CYP3A5, CYP2C8, CYP2C9, CYP2C19, P2Y12, P2Y1 and GPIIIa genes were
      examined using mass spectrometry methods in 396 patients with IS and 378
      controls. Gene-gene interactions were analyzed using generalized multifactor
      dimensionality reduction (GMDR) methods. RESULTS: Single-gene variant analysis
      showed no significant differences in the genotype distributions of the fifteen
      variants between IS patients and controls using the single-locus analytical
      approach. However, GMDR analysis showed a significant gene-gene interaction among
      rs17110453A>C, rs2317676A>G, and rs16863323C>T, which scored 10 for cross
      validation consistency and 9 for the sign test (P = 0.016). Logistic regression
      analysis showed that high-risk interactions among rs17110453A>C, rs2317676A>G,
      and rs16863323C>T were independent risk factor for IS after adjusting for age,
      hypertension, diabetes mellitus, and hemoglobin A1C (OR=2.24, 95% CI: 1.17-5.62,
      P=0.005). CONCLUSIONS: The rs17110453A>C, rs2317676A>G, and rs16863323C>T three
      loci interaction may confer a higher risk for IS. The combinatorial analysis used
      in this study may be helpful to elucidate complex genetic risk factors for IS.

PMID- 29050322
TI  - MicroRNA-466 with tumor markers for cervical cancer screening.
AB  - Cervical cancer is the second most common cancer in women in the world. In this
      study, we explore tumor markers and microRNA-466 combination for cervical cancer
      screening. Tumor markers were measured by the methods of electro-chemiluminescent
      immunoassay and enzyme immunoassay. The microRNA-466 was performed by
      quantitative real-time polymerase chain reaction. Among normal group, hyperplasia
      group and cancer group, the CEA expression levels were 2.26 ng/ml, 3.85 ng/ml and
      16.08 ng/ml, respectively. While the CA125 expression levels were 13.61 u/ml,
      27.32 u/ml and 44.93 u/ml, respectively. The SCCA expression levels were 13.61
      ng/ml, 27.32 ng/ml and 44.93 ng/ml, respectively. The expression levels of tumor
      markers were all gradually increased with the development of cervical lesions.
      The expression levels of microRNA-466 in cervical cancers (0.62) were greater
      than that in normal (0.076) and hyperplasia (0.24). The expression of microRNA
      466 was correlated with lymphnode metastasis (P=0.000). There is a lower overall
      survival rate of patient with large tumor or lymphnode metastasis. Thus, the
      combination of tumor markers and microRNA-466 can be useful for early detection
      of cervical cancer and indicators for advanced stage and prognosis of the
      disease.

PMID- 29050324
TI  - Prognostic and predictive value of metastatic lymph node ratio in stage III
      gastric cancer after D2 nodal dissection.
AB  - INTRODUCTION: This study is to evaluate the prognostic and predictive value of
      metastatic lymph node ratio (MLR) in stage III gastric cancer following radical
      D2 dissection. METHODS: 87 patients who underwent radical resection with D2
      lymphadenectomy were retrospectively evaluated. The median age was 60 with a 2:1
      ratio of male/female. Of these 87 patients, 83 underwent total gastrectomy, the
      remaining 4 underwent subtotal gastrectomy and 57 patients received adjuvant
      chemotherapy with fluoropyrimidines. Indexes of lymph node involvement and other
      clinicopathological data were analyzed. Survival was determined by the Kaplan
      Meier method and log-rank test. Multivariate analysis was performed using the Cox
      proportional hazards model. RESULTS: Median total retrieved lymph node number was
      35 (range: 10-104) with median metastatic lymph node amount of eight (range: 0
      71). Median survival time was 31.7 months with a 3-year survival rate of 36.4%.
      Patients were divided into four groups according to MLR: MLR0, 0; MLR1, <0.1;
      MLR2, 0.1-0.25; MLR3, >0.25. After median follow-up of 31 months, median OS rates
      of MLR0 to MLR3 were 37.1m, 35.9m, 31.5m and 20.8m, respectively (p=0.013).
      Median OS rates were significantly different among subgroups: 39.3m and 36.5m
      were obtained for low subgroups (MLR<0.24) with or without adjuvant chemotherapy,
      respectively; 22.9m and 12.2m were found in high subgroups (MLR>0.24) with and
      without chemotherapy, respectively (p=0.002). Finally, MLR constituted an
      independent prognostic factor in multivariable analysis. CONCLUSIONS: After R0
      resection with D2 lymphadenectomy for stage III gastric cancer, MLR constitutes
      an effective prognostic indicator. Patients with high MLR may benefit the most
      from adjuvant chemotherapy.

PMID- 29050323
TI  - Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and
      suppresses neuroendocrine cancer cell growth in vivo.
AB  - Novel therapies for neuroendocrine (NE) cancers are desperately needed as they
      frequently present as metastatic disease and cause debilitating symptoms by
      secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive
      effect in NE cancer cell lines, and we have observed that histone deacetylase
      inhibitors (HDACi) potently activate Notch. In this study, we describe the
      potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A
      (TDP-A) as a Notch activator and therapeutic agent against NE cancer. IC50 for
      TDP-A was determined to be 4-6 nM in NE cancer cell lines (BON, MZ-CRC-1, and TT)
      without cytotoxicity to lung fibroblasts. The binding characteristics of TDP-A to
      its target HDAC1 was examined using bioluminescence resonance energy transfer
      (BRET). Western blot and flow cytometry analysis showed that TDP-A induces cell
      cycle arrest and apoptosis in a dose-dependent manner. TDP-A dose-dependently
      activated the Notch pathway as measured by increasing functional CBF1-luciferase
      reporter signal and mRNA and protein expressions of Notch isoforms, which were
      attenuated by pretreatment with gamma-secretase inhibitor DAPT. Furthermore, TDP
      A lead to changes in expression level of downstream targets of Notch pathway and
      reduced expression of NE cancer markers. An in vivo study demonstrated that TDP-A
      suppressed NE cancer progression. These results show that TDP-A, as a Notch
      activator, is a promising agent against NE cancers.

PMID- 29050325
TI  - Toll-like receptor 3 pathway restricts Marek's disease virus infection.
AB  - Marek's disease virus (MDV) is an alpha-herpesvirus that causes immune
      suppression and T lymphoma in chickens. Toll-like receptor 3 (TLR3) is critical
      for the host immune response against MDV infection. Previously, our team
      demonstrated that pre-treatment of TLR3 agonist poly (I:C) inhibited Marek's
      disease virus infection in chicken embryo fibroblasts (CEFs). However, whether
      TLR3 inhibits the aggravation of MDV infection is unknown. In the current study,
      we found that TLR3 activation in MDV-infected CEFs effectively inhibited virus
      spread. Using pharmacological approaches, we revealed that pro-inflammatory
      cytokines and interferon-beta induced by TLR3 could restrict Marek's disease
      virus infection. This study contributes to elucidating the function and mechanism
      of the TLR3 pathway in host immune responses against MDV infection.

PMID- 29050326
TI  - Different effection of p.1125Val>Ala and rs11954856 in APC on Wnt signaling
      pathway.
AB  - Colorectal cancer (CRC) is among the most common and fatal forms of solid tumors
      worldwide and more than two thirds of CRC and adenomas patients have APC gene
      mutations. APC is a key regulator in the Wnt/beta-catenin signaling pathway but
      its roles in CRC remains to be elucidated. In this study, we compared APC genes
      between CRC patients and controls to determine possible associations of
      nucleotide changes in the APC gene with the pathways involved in CRC
      pathogenesis. All participants received physical and enteroscopic examinations.
      The APC gene was sequenced for 300 Chinese Han CRC patients and 411 normal
      controls, and the expression levels of genes in the signaling pathway were
      analyzed using Western Blotting. Statistical analyses were conducted using SPSS
      (version 19.0) software. We found that rs11954856 in the APC gene was associated
      with colorectal cancer and could increase the expression levels of APC, beta
      catenin, TCF7L1, TCF7L2 and LEF1 genes in the pathway in the CRC patients,
      demonstrating the involvement of APC in the pathological processes leading to
      CRC.

PMID- 29050327
TI  - Prognostic and predictive value of serum carcinoembryonic antigen levels in
      advanced non-small cell lung cancer patients with epidermal growth factor
      receptor sensitive mutations and receiving tyrosine kinase inhibitors.
AB  - BACKGROUND: Despite the widespread use of epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors (TKIs) in advanced or recurrent non-small cell lung
      cancer (NSCLC), no biomarkers for predicting the efficacy of EGFR-TKIs in
      patients with EGFR-sensitive mutations have yet been identified. The purpose of
      our study was to explore the effect of baseline serum tumor markers in stage
      IIIB/IV NSCLC patients treated with EGFR-TKIs. METHODS: One hundred and seventy
      seven patients with stage IIIB/IV NSCLC who harbored EGFR-sensitive mutations and
      were treated with EGFR-TKIs were retrospectively reviewed. Their levels of CEA,
      CYFRA 21-1, NSE and CA199 were measured before treatment with EGFR-TKIs. RESULTS:
      The response rate for all patients was 54.8%, with a median progression-free
      survival of 6.6 months and overall survival of 14.8 months. In univariate
      analyses, patients with CEA levels below the cutoff point (10 ng/ml) had higher
      RR, better PFS, and better OS than those with CEA levels above 10 ng/mL (RR:
      69.2% vs. 43.4%, p= 0.001; mPFS: 7.8 months vs. 5.3 months, p=0.029; mOS: 18.8
      months vs. 11.8 months, p=0.000). The baseline serum CEA level was an independent
      factor for RR (odds ratio [OR] =0.322, p=0.001), PFS (hazard ratio [HR] =1.45,
      p=0.025), and OS (HR=2.133, p=0.000). CONCLUSION: Our study suggests that
      baseline serum CEA levels may play a role in predicting the efficacy of EGFR-TKIs
      in stage IIIB/IV NSCLC patients with EGFR-sensitive mutations who are treated
      with EGFR-TKIs.

PMID- 29050328
TI  - Prognostic role of pretreatment platelet to lymphocyte ratio in urologic cancer.
AB  - The prognostic value of platelet to lymphocyte ratio (PLR) in urologic cancer
      does not reach a consensus. Herein, we performed the meta-analysis to determine
      the prognostic role of PLR in patients with urologic cancer. A literature search
      was performed in the PubMed, Embase, and Web of Science databases. Hazard ratios
      (HRs) were extracted to estimate the association between PLR and prognosis. A
      total of 20 articles comprising 6079 patients were included in this study. The
      pooled results showed that a high PLR was significantly associated with worse
      prognosis of overall survival (OS) in urologic cancer [HR=1.65, 95% confidence
      interval (CI) =1.37-1.99, P<0.01]. The result also indicated that an elevated PLR
      was significantly associated with poor OS in renal cancer (HR=1.88, 95% CI=1.39
      2.55, P<0.01). In addition, the significant association between poor OS and
      elevated PLR in renal cancer was consistent regardless of treatment, cut-off
      value, sample size and study quality. Our result also indicated that an elevated
      PLR predicted shorter OS (HR=1.78, 95% CI=1.38-2.30, P<0.01) and cancer-specific
      survival (HR=2.02, 95% CI=1.24-3.29, P<0.01) in prostate cancer. In conclusion,
      an elevated PLR was a predictive indicator of poor survival in renal cancer and
      prostate cancer.

PMID- 29050329
TI  - Differentiation between high- and low-grade urothelial carcinomas using contrast
      enhanced ultrasound.
AB  - PURPOSE: To evaluate the value of contrast-enhanced ultrasonography (CEUS) in the
      differentiation of high and low grade urothelial carcinoma. MATERIALS AND
      METHODS: 192 with 192 bladder lesions, including 110 high grade urothelial
      carcinoma and 82 low grade urothelial carcinoma were examined by CEUS. Among 192
      tumors, enhancement patterns of 96 tumors between August 2010 and December 2012
      were analyzed retrospectively. Then from January 2013 to April 2015, compared
      with CEUS was performed on 96 tumors for prospective differential diagnosis.
      Sensitivity, specificity, accuracy, positive predictive value and negative
      predictive value were assessed. RESULTS: With the CEUS view, dominant enhancement
      patterns were revealed as fast wash-in and slow wash-out for high grade
      urothelial carcinoma, fast wash-in and fast wash-out for low grade urothelial
      carcinoma, respectively. At CEUS, the prospective differentiation of bladder
      tumors showed sensitivity 86% , specificity 90%, accuracy 88%, positive
      predictive value 92%, and negative predictive value 82% for high grade tumors,
      while sensitivity 85% , specificity 89%, accuracy 88%, positive predictive value
      85% and negative predictive value 89% for low grade tumors, respectively.
      CONCLUSIONS: Our study demonstrates the great potential of CEUS in the
      differentiation of high and low grade urothelial carcinoma. Since CEUS is an
      effective, inexpensive, and non-invasive method. It could be a reliable tool in
      the evaluation of patients with bladder tumors.

PMID- 29050330
TI  - MiR-196a2 and lung cancer in Chinese non-smoking females: a genetic association
      study and expression analysis.
AB  - BACKGROUND: The common polymorphism rs11614913 in miR-196a2 might be associated
      with lung cancer risk for non-smoking females in northeast China. METHODS: The
      genotypes of rs11614913 in miR-196a2 were determined by a case-control study
      including 1003 patients with lung cancer and 1003 healthy controls. The tissues
      were detected to assess the miRNA expression. Secondary structures of miR-196a2
      were predicted. RESULTS: There was a significant association between miR-196a2
      rs11614913 and lung cancer risk in Chinese non-smoking females. Individuals
      carrying TC or CC genotype had increased risk of lung cancer compared with TT
      genotype (adjusted risks were 1.63 and 1.67). The C allele was associated with a
      higher risk of lung cancer with a significant risk of 1.27. The similar
      significant results were also found in lung adenocarcinoma. There was a
      significant association between miR-196a2 expression and lung cancer risk
      (t=2.594, P=0.012). The relative expression of miR-196a2 was significantly higher
      for CC genotype comparing with the CT or TT genotype in tumor tissues (P values
      were all 0.003). The optimal free energies were different for T allele and C
      allele. CONCLUSIONS: The polymorphism rs11614913 in miR-196a2 may be associated
      with lung cancer risks in Chinese non-smoking females through affecting miR-196a2
      expression and secondary structure.

PMID- 29050331
TI  - A GLO10 score for the prediction of prognosis in high grade gliomas.
AB  - Gliomas are the most common lethal brain tumours and remain great heterogeneity
      in terms of histopathology and clinical outcomes. Among them, glioblastomas are
      the most aggressive tumours that lead to a median of less than one-year survival
      in patients. Despite the little improvement of in diagnosis and treatments for
      last decades, there is an urgent need for prognostic markers to distinguish high-
      and low-risk patients before treatment.Here, we generated a list of genes
      associated with glioblastoma progressions and then performed a comprehensive
      statistical modelling strategy to derive a 10-gene (GLO10) score from genome wide
      expression profiles of a large glioblastoma cohort (n=844). Our study
      demonstrated that the GLO10 score could successfully distinguish high- and low
      risk patients with glioblastomas regardless their traditional pathological
      factors. Validated in four independent cohorts, the utility of GLO10 score could
      provide clinicians a robust prognostic prediction tool to assess risk levels
      upfront treatments.

PMID- 29050332
TI  - Survival outcomes based on systemic agent used concurrently with radiation in
      human-papillomavirus associated oropharyngeal cancer.
AB  - PURPOSE: To investigate survival outcomes of patients treated with concurrent
      cetuximab and radiotherapy for primary management of both HPV positive and
      negative OPSCC, and compare the results to traditional platinum-based therapy. We
      hypothesize that the use of cetuximab in the HPV positive OPSCC patients will
      result in inferior survival based on tumor biological differences. STUDY DESIGN:
      A single institution retrospective analysis of 304 patients. The primary outcomes
      of interest were 1) overall survival and 2) relapse free survival. Pearson Chi
      square tests were used to compare proportions between subgroups. One-way analysis
      of variance was used to compare the continuous variable age between subgroups.
      Kaplan-Meier method was used to produce survival curves, and comparisons between
      survival curves were made using the log-rank test. The survival functions
      comparing subgroups of chemotherapy were analyzed using semi-parametric (i.e. Cox
      proportional hazards models) and fully parametric regression with Weibull
      distributions. Multivariable models were adjusted for age at diagnosis, gender,
      race, chemotherapy, radiotherapy, and cancer stage. RESULTS: In the multivariable
      analysis, the hazard ratio for cetuximab compared to cisplatin or
      carboplatin/paclitaxel was HR=0.77[95% CI = 0.67, 0.90] in the HPV - group,
      suggesting more favorable outcomes for the patients on cetuximab in this group.
      However, in the HPV + cohort, the hazard ratio was 1.88 [95% CI = 1.42, 2.50] for
      those patients treated with cetuximab vs platinum-based therapy. CONCLUSIONS: Our
      data suggest that cetuximab may have inferior outcomes in HPV-associated OPSCC
      compared to traditional platinum-based therapy.

PMID- 29050334
TI  - Detection of active proteasome structures in brain extracts: proteasome features
      of August rat brain with violations in monoamine metabolism.
AB  - The aim of this work was to detect changes in proteasome pools of brain parts of
      August rats with monoamine metabolism violations in comparison with that of
      control Wistar rats. To reveal active proteasome structures, a method of native
      electrophoresis for the analysis of crude tissue fractions was developed. By
      means of this method and following Western blotting, the most pronounced changes
      in reorganization of proteasome structures were detected in proteasome pool of
      the brain cortex of August rats. Main findings are the enhanced expression of
      immune proteasome subtypes containing proteolytic subunit LMP2 and activator
      PA28alphabeta as well as immune proteasome subtypes containing proteolytic
      subunit LMP7 and activator PA700 and simultaneously decreased expression of
      subtypes with subunit LMP2 and activator PA700 in the brain cortex of August rats
      compared to that of Wistar rats. These results were indirectly confirmed by SDS
      PAGE method followed by Western blotting, which showed the increased quantities
      of immune subunits and proteasome activators in the brain cortex of August rats
      compared to that of Wistar rats. Immune proteasomes were revealed by
      immunohistochemistry in neurons, but not in glial cells of August and Wistar rat
      cortex. The detected reorganization of proteasome pools is likely to be important
      for production of special peptides to provide the steady interaction between
      neurons and adaptation of central nervous system to conditions caused by
      monoamine metabolism deviations.

PMID- 29050333
TI  - Characterization of CADD522, a small molecule that inhibits RUNX2-DNA binding and
      exhibits antitumor activity.
AB  - The RUNX2 transcription factor promotes breast cancer growth and metastasis
      through interactions with a variety of cofactors that activate or repress target
      genes. Using a direct drug discovery approach we identified CADD522 as a small
      molecule that inhibits the DNA binding of the runt box domain protein, RUNX2. The
      current study defines the effect of CADD522 on breast cancer growth and
      metastasis, and addresses the mechanisms by which it exerts its anti-tumor
      activity. CADD522 treatment resulted in significant growth inhibition, clonogenic
      survival, tumorsphere formation, and invasion of breast cancer cells. CADD522
      negatively regulated transcription of RUNX2 target genes such as matrix
      metalloproteinase-13, vascular endothelial growth factor and glucose transporter
      1, but upregulated RUNX2 expression by increasing RUNX2 stability. CADD522
      reduced RUNX2-mediated increases in glucose uptake and decreased the level of CBF
      beta and RUNX2 phosphorylation at the S451 residue. These results suggest several
      potential mechanisms by which CADD522 exerts an inhibitory function on RUNX2-DNA
      binding; interference with RUNX2 for the DNA binding pocket, inhibition of
      glucose uptake leading to cell cycle arrest, down-regulation of CBF-beta, and
      reduction of S451-RUNX2 phosphorylation. The administration of CADD522 into MMTV
      PyMT mice resulted in significant delay in tumor incidence and reduction in tumor
      burden. A significant decrease of tumor volume was also observed in a CADD522
      treated human triple-negative breast cancer-patient derived xenograft model.
      CADD522 impaired the lung retention and outgrowth of breast cancer cells in vivo
      with no apparent toxicity to the mice. Therefore, by inhibiting RUNX2-DNA
      binding, CADD522 may represent a potential antitumor drug.

PMID- 29050335
TI  - Evidence for the association of chromatin and microRNA regulation in the human
      genome.
AB  - Both microRNAs (miRNAs) and chromatin regulation play important roles in cellular
      processes and they function at different regulatory levels of transcription.
      Although efforts have been devoted to the investigation of miRNA and chromatin
      regulation, there's still no comprehensive work to illustrate their relationships
      due tothe lack of whole-genome wide datasets in different human cellular
      contexts. Based on the recently published large-scale epigenetic data, we
      examined the association between miRNA and epigenetic machinery. Our work
      confirmed a general relationship between miRNA biogenesis and chromatin features
      around pre-miRNA genomic regions. Obvious enrichments of DNA methylation and
      several histone modifications were observed within the pre-miRNA genomic region,
      which werecorrelated with miRNA expression levels. Furthermore, chromatin
      features at genepromoter regionsweretightly associated with miRNA regulation.
      Interestingly, we found that genes with their promoter regions located in the
      active chromatin state regions tend to have a higher probability to be targeted
      by miRNAs. This worksuggests that miRNAs and chromatin features are often highly
      coordinated, which provides a guide to deeply understand the complexity of gene
      regulation.

PMID- 29050336
TI  - Transcriptional downregulation of microRNA-19a by ROS production and NF-kappaB
      deactivation governs resistance to oxidative stress-initiated apoptosis.
AB  - Cell apoptosis is one of the main pathological alterations during oxidative
      stress (OS) injury. Previously, we corroborated that nuclear factor-kappaB (NF
      kappaB) transactivation confers apoptosis resistance against OS in mammalian
      cells, yet the underlying mechanisms remain enigmatic. Here we report that
      microRNA-19a (miR-19a) transcriptionally regulated by reactive oxygen species
      (ROS) production and NF-kappaB deactivation prevents OS-initiated cell apoptosis
      through cylindromatosis (CYLD) repression. CYLD contributes to OS-initiated cell
      apoptosis, for which NF-kappaB deactivation is essential. MiR-19a directly
      represses CYLD via targeting 3' UTR of CYLD, thereby antagonizing OS-initiated
      apoptosis. CYLD repression by miR-19a restores the IKKbeta phosphorylation, RelA
      disassociation from IkappaBalpha, IkappaBalpha polyubiquitination and
      degradation, RelA recruitment at VEGF gene promoter as well as VEGF secretion in
      the context of OS. Either pharmacological deactivation of NF-kappaB or genetic
      upregulation of CYLD compromises the apoptosis-resistant phenotypes of miR-19a.
      Furthermore, miR-19a is transcriptionally downregulated upon OS in two distinct
      processes that require ROS production and NF-kappaB deactivation. VEGF
      potentiates the ability of miR-19a to activate NF-kappaB and render apoptosis
      resistance. Our findings underscore a putative mechanism whereby CYLD repression
      mediated and NF-kappaB transactivation-dependent miR-19a regulatory feedback loop
      prevents cell apoptosis in response to OS microenvironment.

PMID- 29050337
TI  - Comprehensive immune transcriptomic analysis in bladder cancer reveals subtype
      specific immune gene expression patterns of prognostic relevance.
AB  - Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC)
      have led to its classification into distinct genomic and transcriptomic molecular
      subtypes that exhibit variability in prognosis. Evolving evidence from recent
      immunotherapy trials has demonstrated the significance of pre-existing tumour
      immune profiles that could guide treatment decisions. To identify immune gene
      expression patterns associated with the molecular subtypes, we performed a
      comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic
      data from 347 MIBC cases from The Cancer Genome Atlas (TCGA). To investigate
      subtype-associated immune gene expression patterns, we assembled 924 immune
      response genes and specifically those involved in T-cell cytotoxicity and the
      Type I/II interferon pathways. A set of 157 ranked genes was able to distinguish
      the four subtypes in an unsupervised analysis in an original training cohort
      (n=122) and an expanded, validation cohort (n=225). The most common
      overrepresented pathways distinguishing the four molecular subtypes, included
      JAK/STAT signaling, Toll-like receptor signaling, interleukin signaling, and T
      cell activation. Some of the most enriched biological processes were responses to
      IFN-gamma, antigen processing and presentation, cytokine mediated signaling,
      hemopoeisis, cell proliferation and cellular defense response in the TCGA cluster
      IV. Our novel findings provide further insights into the association between
      genomic subtypes and immune activation in MIBC and may open novel opportunities
      for their exploitation towards precise treatment with immunotherapy.

PMID- 29050338
TI  - Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected
      HCC prolong patient survival.
AB  - BACKGROUND & AIMS: The immunological microenvironment of HCC influences patient
      outcome, however, the role of B cells remains unclear. This study investigated
      effects of local B-cell infiltration in HCC cohorts on patient survival and
      immunological and molecular tumor microenvironment. RESULTS: Unsupervised gene
      expression analysis of full cancer transcriptomes (N=2158) revealed a highly co
      regulated immunological cluster in HCC that mainly contained immunoglobulin
      fragments. More specifically, in an independent patient cohort (N=242) that
      compares HCC with non tumorous liver tissue high expression of these B-cell
      associated genes was associated with better patient outcome (P=0.0149).
      Conclusively, the immunohistochemical analysis of another independent cohort of
      resected HCCs (N=119) demonstrated that infiltration of HCCs by CD20+ cells
      (P=0.004) and CD79a+ cells (P=0.038) at the infiltrative margin were associated
      with prolonged patient survival. Further, the immunoglobulin fragments that were
      identified in the gene expression analysis were detected at high levels in
      patients with dense B-cell infiltration. METHODS: Gene expression of 2
      independent HCC tissue databases was compared using microarrays. Additionally,
      tissue of resected HCCs was stained for CD20, CD79a and immunoglobulins and
      analysed for the respective cell numbers separately for tumor, infiltrative
      margin and distant liver stroma. These findings were correlated with clinical
      data and patient outcome. CONCLUSIONS: Infiltration of HCCs by B cells is
      associated with prolonged patient survival. Further, a distinct B-cell like
      immunoglobulin profile of HCCs was identified that goes along with better patient
      outcome. We suggest that B cells contribute to local tumor control by secreting
      increased levels of immunoglobulins with antitumor activity.

PMID- 29050339
TI  - Aberrant expression of OATP1B3 in colorectal cancer liver metastases and its
      clinical implication on gadoxetic acid-enhanced MRI.
AB  - PURPOSE: To investigate the factors associated with hepatobiliary phase (HBP)
      enhancement at gadoxetic acid-enhanced magnetic resonance imaging (MRI) and to
      determine whether HBP images could be used to predict prognosis in patients with
      colorectal cancer liver metastasis (CRLM). RESULTS: Of the 96 total nodules, 65
      and 31 nodules were in the mixed and clearly hypointense groups, respectively. In
      the 55 nodules without preoperative chemotherapy, organic anionic transporting
      polypeptide 1B3 (OATP1B3) expression was a significant factor regarding the HBP
      enhancement (P=0.042). In this subgroup, nodules with OATP1B3 expression
      displayed a significantly higher relative intensity ratio on the HBP image
      (RIRpost) and relative enhancement ratio (RER) than those lacking this marker
      (P=0.024, 0.003, respectively). No significant factor was associated with the
      enhancement pattern in the chemotherapy group. The mixed hypointense group
      displayed worse survival rates (P=0.002). MATERIALS AND METHODS: Ninety-six
      patients who underwent pre-operative liver MRI and surgical resection for CRLM
      from January 2010 to June 2012 were retrospectively analyzed. We qualitatively
      evaluated the HBP enhancement pattern of CRLMs and classified them into mixed and
      clearly hypointense groups. For quantitative measurement, the RIRpost and RER
      were analyzed. To investigate factors associated with HBP enhancement, tumor
      components (fibrosis, necrosis, and cellularity) and OATP1B3 expression were
      scored on a 4-point scale. Univariate and multivariate analyses were done to
      determine significant factors for visual enhancement and quantitative parameters.
      CONCLUSIONS: OATP1B3 expression is associated with mixed hypointense CRLMs
      without chemotherapy. Signal intensity on HBP has potential usefulness to predict
      prognosis in CRLMs.

PMID- 29050341
TI  - Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting
      inflammation and apoptosis.
AB  - Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely
      used to treat many diseases associated with inflammation and apoptosis. Acute
      lung injury (ALI) is a common clinical disease in humans characterized by
      pulmonary inflammation and apoptosis. In the present study, we investigated the
      protective effects of GOH in a mouse model of ALI induced by the intranasal
      administration of lipopolysaccharide (LPS) and elucidated the underlying
      molecular mechanisms in RAW 264.7 cells. In vivo, GOH treatment markedly
      ameliorated pathological injury and pulmonary cell apoptosis and reduced the
      wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the
      production of pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha). In
      vitro, the levels of pro-inflammatory cytokines, iNOS and COX-2 were
      significantly increased in LPS-stimulated RAW 264.7 cells, an effect that was
      decreased by GOH treatment. Moreover, GOH treatment dramatically reduced the
      expression of Toll-like receptor 4 (TLR4) and then prevented the nuclear factor
      kappaB (NF-kappaB) activation. GOH treatment also promoted anti-apoptotic Bcl-2
      expression and inhibited pro-apoptotic Bax and Caspase-3 expression. Furthermore,
      knockdown of TLR4 expression exerted a similar effect and inhibited the
      phosphorylation of p65, as well as the Bax and Caspase-3 expression. Taken
      together, these results suggest that GOH treatment alleviates LPS-induced ALI via
      inhibiting pulmonary inflammation and apoptosis, a finding that might be
      associated with the inhibition of TLR4-mediated NF-kappaB and Bcl-2/Bax
      signalling pathways.

PMID- 29050340
TI  - NOGO-B promotes EMT in lung fibrosis via MMP14 mediates free TGF-beta1 formation.
AB  - Idiopathic pulmonary fibrosis (IPF) is a lung disease with an extremely poor
      prognosis. Epithelial mesenchymal transition (EMT) appearing on the airway
      epithelial cell plays an essential role in the formation and development of
      Idiopathic pulmonary fibrosis. In this paper, Bleomycin (BLM)-induced mice model
      combined with bioinformatics analysis were employed to elucidate the potential
      mechanism of EMT in pulmonary fibrosis. The obtained results showed that
      endoplasmic reticulum protein Nogo-b may promote MMP14-mediated proprotein
      maturation of TGF-beta1, accelerating the release of free TGF-beta1 in type II
      airway epithelial cells A549, subsquently, induce the epithelial-mesenchymal
      transition (EMT) of the cell. In all, the overexpression of Nogo-b play a role in
      the course of pulmonary fibrosis by influencing the EMT ability of cells.

PMID- 29050342
TI  - Role of the CYP3A4-mediated 11,12-epoxyeicosatrienoic acid pathway in the
      development of tamoxifen-resistant breast cancer.
AB  - Epoxyeicosatrienoic acid (EET) production via cytochrome P450 (CYP) epoxygenases
      closely correlates with the progression of breast cancer. However, its role in
      the development of chemoresistant breast cancers has yet to be elucidated. Here,
      we found that CYP3A4 expression and its epoxy-product, 11,12-epoxyeicosatrienoic
      acid (11,12-EET) was enhanced in tamoxifen (TAM)-resistant MCF-7 (TAMR-MCF-7)
      breast cancer cells compared to control MCF-7 cells. Treatment of TAMR-MCF-7
      cells with ketoconazole and azamulin (selective CYP3A4 inhibitors) or 14,15
      epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an EET antagonist) inhibited cellular
      proliferation and recovered the sensitivity to 4-hydroxytamoxifen. Chick
      chorioallantoic membrane and trans-well migration analyses revealed that the
      enhanced angiogenic, tumorigenic, and migration intensities of TAMR-MCF-7 cells
      were also significantly suppressed by ketoconazole and 14,15-EEZE. We previously
      reported that Pin1, a peptidyl prolyl isomerase, is a crucial regulator for
      higher angiogenesis and epithelial-mesenchymal transition characteristics of TAMR
      MCF-7 cells. EET inhibition suppressed E2F1-dependent Pin1 gene transcription,
      and Pin1 silencing also blocked cell proliferation, angiogenesis, and migration
      of TAMR-MCF-7 cells. Our findings suggest that the CYP3A4-mediated EET pathway
      represents a potential therapeutic target for the treatment of tamoxifen
      resistant breast cancer.

PMID- 29050343
TI  - An integrated multigene expression panel to predict long-term survival after
      curative hepatectomy in patients with hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy.
      To develop an integrated multigene expression panel, 144 patients were randomly
      assigned to either discovery or validation set in a 1:2 ratio. Using surgically
      resected HCC specimens, expression levels of 12 candidate molecular markers were
      determined using quantitative reverse-transcriptase PCR. In the discovery set, an
      expression panel was developed according to the concordance index (C-index)
      values for overall survival from all 4095 combinations of the 12 candidate
      molecular markers. Expression scores was determined with weighting according to
      the coefficient in a Cox regression, and patients were classified into grade 1, 2
      and 3. Reproducibility was then tested in the validation set. A panel consisting
      of four markers, PRMT5, MAGED4, DPYSL3 and AJAP1 was selected as the optimal and
      most well-balanced set with a C-index value of 0.707. Patient prognosis was
      clearly stratified by the expression grade using this panel. In the validation
      set, both overall and disease-free survival rates decreased incrementally with as
      the grade increased. Higher grades were significantly associated with tumor
      multiplicity and vessel invasion. The prevalence of extrahepatic recurrences was
      increased in grade 3 patients. The integrated multigene expression panel clearly
      stratified HCC patients into low, intermediate and high risk.

PMID- 29050344
TI  - MicroRNA-141-3p promotes glioma cell growth and temozolomide resistance by
      directly targeting p53.
AB  - Glioblastoma multiforme is the most common primary malignancy in the brain and
      confers a uniformly poor prognosis. MicroRNAs have been shown to activate or
      inhibit tumorigenesis. Abnormalities in the p53 signaling pathway are found in
      various cancers and correlate with tumor formation. We examined the expression of
      microRNA-141-3p (miR-141-3p) in glioma of different grades by analysis of
      expression profiling databases and clinical specimens. Cell proliferation and
      flow cytometry assays were performed to evaluate the promotion of miR-141-3p in
      proliferation, cell cycle, apoptosis, and temozolomide resistance of glioblastoma
      cells in vitro. Bioinformatics analyses, luciferase reporter assays, and
      immunoblotting showed that p53 is a target gene of miR-141-3p. A significant
      inverse correlation was observed between expression of miR-141-3p and p53 in
      glioma and normal brain tissues (R2=0.506, P<0.0001). Rescue experiments
      indicated that overexpression of p53 significantly reversed the alterations in
      proliferation, cell cycle distribution, and temozolomide resistance measured by
      cell apoptosis induced by miR-141-3p overexpression. In an orthotopic mouse model
      of human glioma, inhibition of miRNA-141-3p reduced the proliferation and growth
      of glioma cells in the brain and significantly prolonged the survival of glioma
      bearing mice. We suggest that miR-141-3p promotes glioblastoma progression and
      temozolomide resistance by altering p53 expression and therefore may serve as a
      new diagnostic marker and therapeutic target for glioma in the future.

PMID- 29050345
TI  - Differential diagnosis of hemangiomas from spinal osteolytic metastases using 3.0
      T MRI: comparison of T1-weighted imaging, chemical-shift imaging, diffusion
      weighted and contrast-enhanced imaging.
AB  - The retrospective study investigated accuracy of quantitative evaluation of T1
      weighted imaging (T1WI) with and without fat suppression (FS), chemical-shift,
      diffusion-weighted imaging (DWI) and enhanced imaging at 3.0 T MRI for
      distinguishing spinal hemangiomas from metastases. 27 patients with 33 spinal
      hemangiomas (15 atypical hemangiomas) and 26 patients with 71 metastases were
      recruited. T1WI, FS T1WI, in- and out-phase, DWI and enhanced T1WI were acquired.
      Signal intensities (SIs) of lesions were obtained. Signal intensity ratios (SIRs)
      and enhancement ratios of lesions in enhanced imaging were assessed. Ratio of SI
      loss of hemangiomas or atypical hemangiomas between T1WI and FS T1WI was higher
      than those of metastases (p < 0.001). The accuracies of ratio of SI loss between
      T1WI and FS T1WI for differentiating hemangiomas and atypical hemangiomas from
      metastases were 96.15% and 91.86%. Ratio of SI loss between in- and out- phase
      could differentiate hemangiomas and atypical hemangiomas from metastases with
      accuracies of 74.04% and 84.88%. Cutoff values for hemangiomas in SIRs of <= 1.52
      (early phase) and <= 1.38 (middle phase) yielded accuracies of 92.31% and 82.69%.
      Enhancement ratios of atypical hemangiomas in middle and delayed phases were
      higher than that of metastases. Accuracies of apparent diffusion coefficient for
      differentiating hemangiomas and atypical hemangiomas from metastases were 70.19%
      and 89.53%. T1WI with and without fat suppression could distinguish spinal
      hemangiomas from metastases. Quantitative assessment of chemical-shift, DWI and
      enhanced imaging were helpful to identification of spinal hemangiomas and
      metastases.

PMID- 29050346
TI  - Identification of candidate genes related to pancreatic cancer based on analysis
      of gene co-expression and protein-protein interaction network.
AB  - Pancreatic cancer (PC) is one of the most common causes of cancer mortality
      worldwide. As the genetic mechanism of this complex disease is not uncovered
      clearly, identification of related genes of PC is of great significance that
      could provide new insights into gene function as well as potential therapy
      targets. In this study, we performed an integrated network method to discover PC
      candidate genes based on known PC related genes. Utilizing the subnetwork
      extraction algorithm with gene co-expression profiles and protein-protein
      interaction data, we obtained the integrated network comprising of the known PC
      related genes (denoted as seed genes) and the putative genes (denoted as linker
      genes). We then prioritized the linker genes based on their network information
      and inferred six key genes (KRT19, BARD1, MST1R, S100A14, LGALS1 and RNF168) as
      candidate genes of PC. Further analysis indicated that all of these genes have
      been reported as pancreatic cancer associated genes. Finally, we developed an
      expression signature using these six key genes which significantly stratified PC
      patients according to overall survival (Logrank p = 0.003) and was validated on
      an independent clinical cohort (Logrank p = 0.03). Overall, the identified six
      genes might offer helpful prognostic stratification information and be suitable
      to transfer to clinical use in PC patients.

PMID- 29050347
TI  - Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma.
AB  - We conducted a meta-analysis to assess the efficacy and safety of dose-dense
      chemotherapy in the treatment of patients with urothelial carcinoma. A systematic
      search was conducted in PubMed, Medline, Embase, Web of Science and Cochrane
      Collaboration's Central register of controlled trials (CENTRAL) for relevant
      articles. Data was obtained from 10 trials with a total of 1093 patients. The
      pooled pathologic complete response (pCR) was 27.8% in the ten studies with a
      full cohort of 684 patients who received dose-dense methotrexate, vinblastine,
      adriamycin and cisplatin (dd-MVAC). In the controlled trials, although the
      difference was not significant, the pCR rate in the dd-MVAC group has a trend of
      increase (odds ratio (OR) 1.52; 95% confidence interval (CI) 0.78-2.98, P = 0.22)
      compared with classic MVAC group. A significant improvement of overall survival
      (OS) (hazard ratio (HR) 0.77, 95% CI 0.61-0.97, p = 0.03) was also observed.
      Hematologic toxicities were the most frequent grade >= 3 toxicities including
      neutropenia/febrile neutropenia (17.5%), anemia (9.4%) and thrombocytopenia
      (6.1%). Compared with the classic MVAC group, dd-MVAC was associated with
      significantly decreased risks of all-grade adverse events (AEs) such as anemia
      (OR 0.457, 95% CI 0.249-0.840, p = 0.012), febrile neutropenia (OR 0.398 95% CI
      0.233-0.681, p = 0.001), and neutropenia (OR 0.373, 95% CI 0.201-0.691, p =
      0.002). In conclusion, dose-dense chemotherapy was effective and tolerable in
      patients with urothelial carcinoma, which could be considered as a reasonable
      therapeutic option.

PMID- 29050348
TI  - Imatinib dose escalation versus sunitinib as a second-line treatment against
      advanced gastrointestinal stromal tumors: A nationwide population-based cohort
      study.
AB  - BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal
      tumor (GIST) patients has led to significant clinical benefits, the disease will
      eventually progress due to imatinib resistance. Treatment options after failure
      of first-line imatinib include imatinib dose escalation or shifting to sunitinib.
      However, there is no large-scale study to compare the efficacy difference between
      these two treatment strategies or the role of surgery. RESULTS: This study
      recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups
      1, 2, and 3, respectively. Groups 1 and 2 had significantly longer overall
      survival (OS) as compared with the group 3 (median 37.5 months versus 16.0
      months; p < 0.0001). After adjusting for confounding variables, groups 1 and 2
      had longer OS than group 3. A favorable survival trend was seen with surgery,
      although this benefit disappeared after adjusting for confounding factors.
      MATERIALS AND METHODS: We conducted a nationwide population-based cohort study
      using data from the Taiwan National Health Insurance Research Database from July
      2004 to December 2010. Advanced GIST patients who no longer responded to first
      line imatinib were stratified into three groups: imatinib dose escalation (group
      1); imatinib dose escalation and a shift to sunitinib (group 2); a direct shift
      to sunitinib (group 3). The therapeutic success of the three treatment regimens
      and the effect of surgery were evaluated by overall survival. CONCLUSIONS: For
      advanced GIST patients who failed first-line imatinib treatment, imatinib dose
      escalation confers significantly longer OS compared to a direct switch to
      sunitinib. Surgery does not provide survival benefits.

PMID- 29050349
TI  - Nomograms incorporated serum direct bilirubin level for predicting prognosis in
      stages II and III colorectal cancer after radical resection.
AB  - An elevated serum bilirubin has been reported to be associated with a reduced
      risk of some cancer; however, the prognostic significance of serum bilirubin in
      colorectal cancer wasn't fully understood. The purpose of this study was to
      evaluate whether serum bilirubin could predict the prognosis of patients in
      stages II and III colorectal cancer. A retrospective cohort of 986 patients with
      colorectal cancer who received surgical resection between January 2005 and
      December 2010 was included in the study. Levels for serum bilirubin were obtained
      from medical records. Survival analysis was used to evaluate the predictive value
      of bilirubin. Serum direct bilirubin (DBIL) was validated as a significant
      prognostic factor by univariate cox regression test for both overall survival
      (OS) and disease free survival (DFS) (P < 0.05). X-tile program identified 3.6 as
      optimal cutoff values for DBIL in terms of OS and DFS. Patients were then divided
      into DBIL high (DBIL >= 3.60 MUmol/l) and low group (DBIL < 3.60 MUmol/l)
      according to the optimal cutoff. High DBIL had higher percentage of lymph node
      metastasis and lymphovascular invasion as compared with low DBIL levels (P <
      0.05). Multivariate cox regression analyses confirmed that high DBIL level was an
      independently prognostic factor for both OS (HR: 1.337, 95% CI: 1.022-1.748, P =
      0.034) and DFS (HR: 1.312, 95% CI: 1.049-1.643, P = 0.018). In addition,
      nomograms on OS and DFS were established according to all significant factors,
      and c-indexes were 0.715 (95% CI: 0.683-0.748) and 0.704 (95% CI: 0.678-0.730),
      respectively. Nomograms based on OS and DFS can be recommended as practical
      models to evaluate prognosis for CRC patients.

PMID- 29050350
TI  - Surgical resection for hepatic metastasis from gastric cancer: a multi-
      institution study.
AB  - BACKGROUND: The beneficial effect of surgical resection for hepatic metastasis
      from gastric cancer (HMGC) remains elusive. This study was conducted to analyze
      surgical outcomes of HMGC and determine the prognostic factors associated with
      survival. RESULTS: The in-hospital mortality rate was zero, and the overall
      morbidity rate was 56%. The overall 1-, 3-, and 5-year survival rate after
      surgery was 87.5%, 47.6%, and 21.7%, respectively, with a median survival time of
      34.0 months. Multiple liver metastases (hazard ratio [HR] =1.998; 95% confidence
      interval [CI] = 1.248-3.198; P = 0.004) and >= T3 stage of the primary gastric
      cancer (HR = 2.065; 95% CI = 1.201-3.549; P = 0.009) were independent prognostic
      determinants in the multivariate analysis. MATERIALS AND METHODS: Data on
      surgical resection of 96 patients with HMGC at six institutions in China were
      analysed retrospectively. Prognostic factors were assessed by multiple stepwise
      regression analysis using the Cox model. CONCLUSIONS: Surgical resection for HMGC
      is feasible and beneficial to long-term survival in selected patients.

PMID- 29050351
TI  - The prognostic significance of preoperative left ventricular diastolic
      dysfunction and left atrial enlargement on acute coronary syndrome in kidney
      transplantation.
AB  - Echocardiography is commonly performed as a screening test to evaluate
      perioperative risks before kidney transplantation. However, only limited data are
      available on echocardiographic parameters of left ventricular diastolic
      dysfunction (LVDD) and left atrial enlargement (LAE) on acute coronary syndrome
      and mortality in kidney transplant recipients. We reviewed 2779 adult recipients
      who underwent pretransplant echocardiography from 1997 to 2012. We divided the
      patients into two and four groups by two categories: LVDD grades 0-1 vs. 2-3, and
      left atrial size quartile groups. During a mean follow-up of 4.5 years, acute
      coronary syndrome occurred in 89 (3.2%) patients. The recipients with LVDD grades
      2-3 (P = 0.005 for non-fatal, P = 0.02 for fatal/non-fatal) and LAE (P = 0.001
      for non-fatal, P = 0.03 for fatal/non-fatal) had a higher incidence of acute
      coronary syndrome after kidney transplantation. All-cause mortality did not
      differ significantly between the groups. In a multivariate analysis, LVDD of
      grades 2-3 (hazard ratio 2.98, 95% confidence interval 1.535-5.787; P = 0.001),
      and LAE (hazard ratio 1.052, 95% confidence interval 1.006-1.101; P = 0.03) were
      independently associated with non-fatal acute coronary syndrome. In patients who
      are kidney transplant candidates, pretransplant LVDD and LAE were independently
      associated with a higher incidence of acute coronary syndrome after kidney
      transplantation.

PMID- 29050352
TI  - RAS testing and cetuximab treatment for metastatic colorectal cancer: a cost
      effectiveness analysis in a setting with limited health resources.
AB  - PURPOSE: To test the cost-effectiveness of cetuximab plus irinotecan,
      fluorouracil, and leucovorin (FOLFIRI) as first-line treatment in patients with
      metastatic colorectal cancer (mCRC) from a Chinese medical insurance perspective.
      RESULTS: Baseline analysis showed that the addition of cetuximab increased
      quality-adjusted life-years (QALYs) by 0.63, an increase of $17,086 relative to
      FOLFIRI chemotherapy, resulting in an incremental cost-effectiveness ratio (ICER)
      of $27,145/QALY. When the patient assistance program (PAP) was available, the
      ICER decreased to $14,049/QALY, which indicated that the cetuximab is cost
      effective at a willingness-to-pay threshold of China ($22,200/QALY). One-way
      sensitivity analyses showed that the median overall survival time for the
      cetuximab was the most influential parameter. METHODS: A Markov model by
      incorporating clinical, utility and cost data was developed to evaluate the
      economic outcome of cetuximab in mCRC. The lifetime horizon was used, and
      sensitivity analyses were carried out to test the robustness of the model
      results. The impact of PAP was also evaluated in scenario analyses. CONCLUSIONS:
      RAS testing with cetuximab treatment is likely to be cost-effective for patients
      with mCRC when PAP is available in China.

PMID- 29050353
TI  - Combined efficacy of C-reactive protein and red blood cell distribution width in
      prognosis of patients with culture-negative infective endocarditis.
AB  - OBJECTIVE: To evaluate the combined effect of C-reactive protein (CRP) and red
      blood cell distribution width (RDW) on the prediction of in-hospital and long
      term poor outcomes in patients with blood culture-negative infective endocarditis
      (BCNE). RESULTS: Patients with high CRP and high RDW has the highest incidence of
      in-hospital death (2.3% vs. 7.8% vs. 5.6% vs. 17.5%, P < 0.001). CRP > 17.8 mg/L
      (odds ratio [OR]=2.41, 95% confidence interval [CI], 1.06-5.51, P = 0.037), RDW
      >16.3 (OR = 2.29, 95% CI, 1.10-4.77, P = 0.027), and these two values in
      combination (OR = 3.15, 95% CI, 1.46-6.78, P=0.003) were independently associated
      with in-hospital death. Patients with RDW > 16.3 had higher long-term mortality
      (P = 0.003), while no significant correlation was observed for CRP (P = 0.151).
      MATERIALS AND METHODS: In total, 572 participants with BCNE were consecutively
      enrolled. They were classified into four groups based on the optimal CRP and RDW
      cut-off values (which were determined using a receiver operating characteristic
      analysis): low CRP and low RDW (n = 216), high CRP and low RDW (n = 129), low CRP
      and high RDW (n = 107), and high CRP and high RDW (n = 120). CONCLUSIONS:
      Increased CRP and RDW, especially in combination, are independently associated
      with in-hospital death in BCNE. RDW, but not CRP, has long-term prognostic value.

PMID- 29050354
TI  - Phase I study of nivolumab combined with IFN-beta for patients with advanced
      melanoma.
AB  - The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so
      nivolumab-based combined therapies that enhance anti-tumor immune responses in
      patients with metastatic melanoma are of great interest to dermato-oncologists.
      As we have previously reported, IFN-beta enhances the anti-tumor immune response
      of anti-PD-1 antibodies against B16F10 melanoma in vivo. To explore the potential
      of this property of IFN-beta as part of a combination therapy for the treatment
      of metastatic melanoma patients, we performed a phase 1 trial, using a
      traditional rule-based 3 + 3 design, on patients with advanced melanoma. The
      nivolumab dose was fixed at 2 mg/kg, every 3 weeks. IFN-beta was administered to
      three groups at doses of 1 million, 2 million, and 3 million units, respectively.
      Dose-limiting toxicities were defined as any grade 3-5 adverse events occurring
      between day 0 and day 42 that might possibly be related to nivolumab and IFN
      beta. Of the nine patients who received this combined therapy, none experienced
      dose-limiting toxicities, and all completed the treatment phase of the study.
      Patient follow-up continued for 6 months following the final treatment. There
      were two complete responses (22%) and one partial response (11%), all of which
      occurred in patients who had received monthly IFN-beta immediately prior to the
      study. In this study, we determined the safe dose of IFN-beta, when combined with
      nivolumab, to be 3 million units. To determine the efficacy of this combination
      therapy, further phase II trials are required.

PMID- 29050355
TI  - Dual time-point 18F-FDG PET/CT imaging with multiple metabolic parameters in the
      differential diagnosis of malignancy-suspected bone/joint lesions.
AB  - The purpose of this study was to evaluate the diagnostic potential of dual time
      point18F-FDG PET/CT imaging with multiple metabolic parameters in malignancy
      suspected bone/joint lesions. Fifty seven consecutive patients were recruited.
      PET parameters including SUVmax, SUVmean, metabolic tumor volume (MTV), total
      lesional glycolysis (TLG) and retention indexes (RIs) were obtained. Thirty five
      malignant and 22 benign lesions were confirmed by pathology. In all, 48 receiver
      operating characteristic (ROC) curves were derived. For SUVmax, MTV2.0, TLG2.0,
      MTV2.5 and TLG2.5, areas under the curves (AUCs) of early time-point imaging were
      similar to those of delayed time (P > 0.05), while higher than those of dual time
      (P< 0.05). For MTV50%max, TLG50%max, MTV75%max and TLG75%max, AUCs of early time
      point imaging were lower than those of delayed time (P< 0.05), while similar to
      those of dual time (P> 0.05). In conclusion, dual time-point18F-FDG PET/CT
      imaging shows limited value in the differential diagnosis of malignancy-suspected
      bone/joint lesions. However, MTV and TLG at a fixed SUV threshold (50% or 75% of
      SUVmax) in delayed time-point imaging may provide better diagnostic accuracy.

PMID- 29050356
TI  - Negative lymph node count is a significant prognostic factor in patient with
      stage IV gastric cancer after palliative gastrectomy.
AB  - Negative lymph node (NLN) count has been validated as a protective predictor in
      various cancers after radical resection. However, the prognostic value of NLN
      count in the setting of stage IV gastric cancer patients who have received
      palliative resection has not been investigated. Surveillance, Epidemiology, and
      End Results Program (SEER)-registered gastric cancer patients were used for
      analysis in this study. Kaplan-Meier survival curves and multivariate Cox
      proportional hazards model were used to assess the risk factors for patients'
      survivals. The results showed that NLN count and N stage were independently
      prognostic factors in patients with stage IV gastric cancer after palliative
      surgery (P< 0.001). X-tile plots identified 2 and 11 as the optimal cutoff values
      to divide the patients into high, middle and low risk subsets in term of cause
      specific survival (CSS). And NLN count was proved to be an independently
      prognostic factor in multivariate Cox analysis (P< 0.001). The risk score of NLN
      counts demonstrated that the plot of hazard ratios (HRs) for NLN counts sharply
      increased when the number of NLN counts decreased. Collectively, our present
      study revealed that NLN count was an independent prognostic predictor in stage IV
      gastric cancer after palliative resection. Standard lymph node dissection, such
      as D2 lymphadectomy maybe still necessary during palliative resection for
      patients with metastatic gastric cancer.

PMID- 29050357
TI  - OncomiR-17-5p: alarm signal in cancer?
AB  - Soon after microRNAs entered the stage as novel regulators of gene expression,
      they were found to regulate -and to be regulated by- the development, progression
      and aggressiveness of virtually all human types of cancer. Therefore, miRNAs in
      general harbor a huge potential as diagnostic and prognostic markers as well as
      potential therapeutic targets in cancer. The miR-17-92 cluster was found to be
      overexpressed in many human cancers and to promote unrestrained cell growth, and
      has therefore been termed onco-miR-1. In addition, its expression is often
      dysregulated in many other diseases. MiR-17-5p, its most prominent member, is an
      essential regulator of fundamental cellular processes like proliferation,
      autophagy and apoptosis, and its deficiency is neonatally lethal in the mouse.
      Many cancer types are associated with elevated miR-17-5p expression, and the
      degree of overexpression might correlate with cancer aggressiveness and
      responsiveness to chemotherapeutics - suggesting miR-17-5p to be an alarm signal.
      Liver, gastric or colorectal cancers are examples where miR-17-5p has been
      observed exclusively as an oncogene, while, in other cancer types, like breast,
      prostate and lung cancer, the role of miR-17-5p is not as clear-cut, and it might
      also act as tumor-suppressor. However, in all cancer types studied so far, miR-17
      5p has been found at elevated levels in the circulation. In this review, we
      therefore recapitulate the current state of knowledge about miR-17-5p in the
      context of cancer, and suggest that elevated miR-17-5p levels in the plasma might
      be a sensitive and early alarm signal for cancer ('alarmiR'), albeit not a
      specific alarm for a specific type of tumor.

PMID- 29050358
TI  - State-of-the-art considerations in small cell lung cancer brain metastases.
AB  - BACKGROUND: Small cell lung cancer (SCLC) frequently leads to development of
      brain metastases. These unfortunately continue to be associated with short
      survival. Substantial advances have been made in our understanding of the
      underlying biology of disease. This understanding on the background of previously
      evaluated and currently utilized therapeutic treatments can help guide the next
      steps in investigations into this disease with the potential to influence future
      treatments. DESIGN: A comprehensive review of the literature covering
      epidemiology, pathophysiology, imaging characteristics, prognosis, and
      therapeutic management of SCLC brain metastases was performed. RESULTS: SCLC
      brain metastases continue to have a poor prognosis. Both unique aspects of SCLC
      brain metastases as well as features seen more universally across other solid
      tumor brain metastases are discussed. Systemic therapeutic studies and
      radiotherapeutic approaches are reviewed. CONCLUSIONS: A clearer understanding of
      SCLC brain metastases will help lay the framework for studies which will
      hopefully translate into meaningful therapeutic options for these patients.

PMID- 29050359
TI  - Next-generation sequencing in chronic lymphocytic leukemia: recent findings and
      new horizons.
AB  - The rapid progress in next-generation sequencing technologies has significantly
      contributed to our knowledge of the genetic events associated with the
      development, progression and treatment resistance of chronic lymphocytic leukemia
      patients. Together with the discovery of new driver mutations, next-generation
      sequencing has revealed an immense degree of both intra- and inter-tumor
      heterogeneity and enabled us to describe marked clonal evolution. Advances in
      immunogenetics may be implemented to detect minimal residual disease more
      sensitively and to track clonal B cell populations, their dynamics and molecular
      characteristics. The interpretation of these aspects is indispensable to
      thoroughly examine the genetic background of chronic lymphocytic leukemia. We
      review and discuss the recent results provided by the different next-generation
      sequencing techniques used in studying the chronic lymphocytic leukemia genome,
      as well as future perspectives in the methodologies and applications.

PMID- 29050361
TI  - BET inhibitors as novel therapeutic agents in breast cancer.
AB  - Tumoral cells not only depend on oncogenic abnormalities to maintain its
      malignant phenotype but on non-oncogenic vulnerabilities. Targeting epigenomics
      can modify specific cellular functions required for malignant transformation. The
      Bromodomain (BRD) family mediates their effect by recruiting proteins of the
      transcription machinery, recognizing acetylated-lysine residues in nucleosomal
      histones. Bromodomain and extra-terminal (BET) inhibitors have shown to produce
      growth inhibition in several tumors through the inhibition of the expression of
      several transcription factors. In this review we will discuss the current
      knowledge regarding BET inhibitors in breast cancer. Recent data demonstrates
      their antiproliferative effect in several cancer subtypes, including the triple
      negative subtype, or when combined with cell signaling inhibitors. We will also
      describe options for therapeutic combinations or potential mechanisms of
      resistance, with special emphasis on their future clinical development.

PMID- 29050363
TI  - Role of PLZF as a tumor suppressor in prostate cancer.
AB  - The promyelocytic leukemia zinc finger (PLZF), also known as ZBTB16 (Zinc Finger
      And BTB Domain Containing 16), is a transcription factor involved in the
      regulation of diverse biological processes, including cell proliferation,
      differentiation, organ development, stem cell maintenance and innate immune cell
      development. A number of recent studies have now implicated PLZF in cancer
      progression as a tumor suppressor. However, in certain cancer types, PLZF may
      function as an oncoprotein. Here, we summarize our current knowledge on the role
      of PLZF in various cancer types, in particular prostate cancer, including its
      deregulation, genomic alterations and potential functions in prostate cancer
      progression.

PMID- 29050362
TI  - miR-708-5p: a microRNA with emerging roles in cancer.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene
      expression post-transcriptionally. They are crucial for normal development and
      maintaining homeostasis. Researchers have discovered that dysregulated miRNA
      expression contributes to many pathological conditions, including cancer. miRNAs
      can augment or suppress tumorigenesis based on their expression and transcribed
      targetome in various cell types. In recent years, researchers have begun to
      identify miRNAs commonly dysregulated in cancer. One recently identified miRNA,
      miR-708-5p, has been shown to have profound roles in promoting or suppressing
      oncogenesis in a myriad of solid and hematological tumors. This review highlights
      the diverse, sometimes controversial findings reported for miR-708-5p in cancer,
      and the importance of further exploring this exciting miRNA.

PMID- 29050360
TI  - Immunomodulatory and antitumor effects of type I interferons and their
      application in cancer therapy.
AB  - During the last decades, the pleiotropic antitumor functions exerted by type I
      interferons (IFNs) have become universally acknowledged, especially their role in
      mediating interactions between the tumor and the immune system. Indeed, type I
      IFNs are now appreciated as a critical component of dendritic cell (DC) driven T
      cell responses to cancer. Here we focus on IFN-alpha and IFN-beta, and their
      antitumor effects, impact on immune responses and their use as therapeutic
      agents. IFN-alpha/beta share many properties, including activation of the JAK
      STAT signaling pathway and induction of a variety of cellular phenotypes. For
      example, type I IFNs drive not only the high maturation status of DCs, but also
      have a direct impact in cytotoxic T lymphocytes, NK cell activation, induction of
      tumor cell death and inhibition of angiogenesis. A variety of stimuli, including
      some standard cancer treatments, promote the expression of endogenous IFN
      alpha/beta, which then participates as a fundamental component of immunogenic
      cell death. Systemic treatment with recombinant protein has been used for the
      treatment of melanoma. The induction of endogenous IFN-alpha/beta has been
      tested, including stimulation through pattern recognition receptors. Gene
      therapies involving IFN-alpha/beta have also been described. Thus, harnessing
      type I IFNs as an effective tool for cancer therapy continues to be studied.

PMID- 29050364
TI  - LncRNAs: key players and novel insights into diabetes mellitus.
AB  - Long non-coding RNAs (LncRNAs) are a class of endogenous RNA molecules, which
      have a transcribing length of over 200 nt, lack a complete functional open
      reading frame (ORF), and rarely encode a functional short peptide. Recent studies
      have revealed that disruption of LncRNAs levels correlates with several human
      diseases, including diabetes mellitus (DM), a complex multifactorial metabolic
      disorder affecting more than 400 million people worldwide. LncRNAs are emerging
      as pivotal regulators in various biological processes, in the progression of DM
      and its associated complications, involving pancreatic beta-cell disorder,
      insulin resistance, and epigenetic regulation, etc. Further investigation into
      the mechanisms of action of LncRNAs in DM will be of great value in the thorough
      understanding of pathogenesis. However, prior to successful application of
      LncRNAs, further search for molecular biomarkers and drug targets to provide a
      new strategy for DM prevention, early diagnosis, and therapy is warranted.

PMID- 29050368
TI  - Striatal dysfunction during dual-task performance in Parkinson's disease.

PMID- 29050365
TI  - Mitochondrial genome variation and prostate cancer: a review of the mutational
      landscape and application to clinical management.
AB  - Prostate cancer is a genetic disease. While next generation sequencing has
      allowed for the emergence of molecular taxonomy, classification is restricted to
      the nuclear genome. Mutations within the maternally inherited mitochondrial
      genome are known to impact cancer pathogenesis, as a result of disturbances in
      energy metabolism and apoptosis. With a higher mutation rate, limited repair and
      increased copy number compared to the nuclear genome, the clinical relevance of
      mitochondrial DNA (mtDNA) variation requires deeper exploration. Here we provide
      a systematic review of the landscape of prostate cancer associated mtDNA
      variation. While the jury is still out on the association between inherited mtDNA
      variation and prostate cancer risk, we collate a total of 749 uniquely reported
      prostate cancer associated somatic mutations. Support exists for number of
      somatic events, extent of heteroplasmy, and rate of recurrence of mtDNA
      mutations, increasing with disease aggression. While, the predicted pathogenic
      impact for recurrent prostate cancer associated mutations appears negligible,
      evidence exists for carcinogenic mutations impacting the cytochrome c oxidase
      complex and regulating metastasis through elevated reactive oxygen species
      production. Due to a lack of lethal cohort analyses, we provide additional
      unpublished data for metastatic disease. Discussing the advantages of mtDNA as a
      prostate cancer biomarker, we provide a review of current progress of including
      elevated mtDNA levels, of a large somatic deletion, acquired tRNAs mutations,
      heteroplasmy and total number of somatic events (mutational load). We confirm via
      meta-analysis a significant association between mtDNA mutational load and
      pathological staging at diagnosis or surgery (p < 0.0001).

PMID- 29050366
TI  - The resistance mechanisms and treatment strategies for EGFR-mutant advanced non
      small-cell lung cancer.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have been
      established as the standard therapy for EGFR-sensitizing mutant advanced non
      small-cell lung cancer (NSCLC). However, patients ultimately develop resistance
      to these drugs. There are several mechanisms of both primary and secondary
      resistance to EGFR-TKIs. The primary resistance mechanisms include point
      mutations in exon 18, deletions or insertions in exon 19, insertions,
      duplications and point mutations in exon 20 and point mutation in exon 21 of EGFR
      gene. Secondary resistance to EGFR-TKIs is due to emergence of T790M mutation,
      activation of alternative signaling pathways, bypassing downstream signaling
      pathways and histological transformation. Strategies to overcome these intrinsic
      and acquired resistance mechanisms are complex. With the development of the
      precision medicine for advanced NSCLC, available systemic and local treatment
      options have expanded, requiring new clinical algorithms that take into account
      resistance mechanism. Though combination therapy is emerging as the standard of
      to overcome resistance mechanisms. Personalized treatment modalities based on
      molecular diagnosis and monitoring is essential for disease management. Emerging
      data from the ongoing clinical trials on combination therapy of third generation
      TKIs and antibodies in EGFR mutant NSCLC are promising for better survival
      outcomes.

PMID- 29050367
TI  - Expression and clinical association of programmed cell death-1, programmed death
      ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent.
AB  - In order to explore the potential of immune checkpoint blockade in sarcoma, we
      investigated expression and clinical relevance of programmed cell death-1 (PD-1),
      programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients.
      Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar
      rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma
      (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined
      immunohistochemically. PD-L1 expression was predominantly detected in alveolar
      and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar
      subtype PD-L1 expression was associated with better overall, event-free and
      metastases-free survival. PD-1 expression on lymphocytes was predominantly seen
      in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly
      detected in osteosarcomas (35%) and associated with worse event-free survival in
      synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of
      on tumor infiltrating lymphocytes. Overall, expression and clinical associations
      were found to be subtype dependent. For the first time PD-1 expression on Ewing
      sarcoma (19%) and DSRCT (82%) tumor cells was described.

PMID- 29050369
TI  - New hope for devastating neurodegenerative disease.

PMID- 29050370
TI  - Knowing your enemy: from post-mortem scene reconstruction to real-time monitoring
      of the spread of tau and amyloid.

PMID- 29050371
TI  - The life and legacy of Brown-Sequard.

PMID- 29050372
TI  - Abnormal white matter development in children with multiple sclerosis and
      monophasic acquired demyelination.

PMID- 29050373
TI  - Editorial.

PMID- 29050374
TI  - Taxonomic structure and functional association of foxtail millet root microbiome.
AB  - The root microbes play pivotal roles in plant productivity, nutrient uptakes, and
      disease resistance. The root microbial community structure has been extensively
      investigated by 16S/18S/ITS amplicons and metagenomic sequencing in crops and
      model plants. However, the functional associations between root microbes and host
      plant growth are poorly understood. This work investigates the root bacterial
      community of foxtail millet (Setaria italica) and its potential effects on host
      plant productivity. We determined the bacterial composition of 2882 samples from
      foxtail millet rhizoplane, rhizosphere and corresponding bulk soils from 2 well
      separated geographic locations by 16S rRNA gene amplicon sequencing. We
      identified 16 109 operational taxonomic units (OTUs), and defined 187 OTUs as
      shared rhizoplane core OTUs. The beta-diversity analysis revealed that
      microhabitat was the major factor shaping foxtail millet root bacterial
      community, followed by geographic locations. Large-scale association analysis
      identified the potential beneficial bacteria correlated with plant high
      productivity. Besides, the functional prediction revealed specific pathways
      enriched in foxtail millet rhizoplane bacterial community. We systematically
      described the root bacterial community structure of foxtail millet and found its
      core rhizoplane bacterial members. Our results demonstrated that host plants
      enrich specific bacteria and functions in the rhizoplane. The potentially
      beneficial bacteria may serve as a valuable knowledge foundation for bio
      fertilizer development in agriculture.

PMID- 29050375
TI  - Interstitial fluid pressure of thymic epithelial tumours.
AB  - Tumours show an increased interstitial fluid pressure, which correlates with
      various pathophysiological features. Moreover, interstitial fluid pressure is a
      prognostic factor for cervical and lung cancer. However, there have been no
      reports on the usefulness of measuring interstitial fluid pressure in thymic
      epithelial tumours. Therefore, this study aimed to examine the relationship
      between interstitial fluid pressure and the clinicopathological characteristics
      of thymic epithelial tumours. Interstitial fluid pressure was prospectively
      measured at the centre of the tumour using a 1-Fr Mikro-Tip sensor catheter in 44
      patients with thymic epithelial tumours, 40 with thymomas and 4 with thymic
      carcinomas. Data from these 44 patients were analysed for correlations between
      interstitial fluid pressure and clinicopathological and demographic factors
      including sex, age, tumour size, World Health Organization histological subtypes,
      myasthenia gravis, capsular invasion, mediastinal pleura invasion, lung invasion,
      pericardium invasion, dissemination, Masaoka-Koga stage, maximal standardized
      uptake value and recurrence-free survival (RFS). The mean interstitial fluid
      pressure was 11.3 mmHg; interstitial fluid pressure was significantly correlated
      with maximal standardized uptake value, lung invasion, dissemination and Masaoka
      Koga stage. Low interstitial fluid pressure (<=14 mmHg) showed a tendency for
      better RFS compared with high interstitial pressure (P = 0.053). Lung invasion,
      dissemination and Masaoka-Koga stage were correlated with RFS in univariable
      analysis; lung invasion was selected as an independent prognostic factor in
      multivariable analysis. On the basis of these results, interstitial fluid
      pressure of thymic epithelial tumours has been shown to correlate with their
      clinicopathological features.

PMID- 29050377
TI  - Oscillatory coupling of the subthalamic nucleus in obsessive compulsive disorder.

PMID- 29050379
TI  - Erratum.

PMID- 29050378
TI  - Reply: Oscillatory coupling of the subthalamic nucleus in obsessive compulsive
      disorder.

PMID- 29050380
TI  - Inflammasomes in neurological diseases: emerging pathogenic and therapeutic
      concepts.
AB  - Inflammasome activation in the central nervous system occurs in both health and
      disease. Inflammasomes are cytosolic protein complexes that sense specific
      infectious or host stimuli and initiate inflammatory responses through caspase
      activation. Assembly of inflammasomes results in caspase-1-mediated proteolytic
      cleavage and release of the pro-inflammatory cytokines, interleukin-1beta and
      interleukin-18, with initiation of pyroptosis, an inflammatory programmed cell
      death. Recent developments in the inflammasome field have uncovered novel
      molecular mechanisms that contribute to a broad range of neurological disorders
      including those associated with specific mutations in inflammasome genes as well
      as diseases modulated by inflammasome activation. This update focuses on recent
      developments in the field of inflammasome biology highlighting different
      inflammasome activators and pathways discovered in the nervous system. We also
      discuss targeted therapies that regulate inflammasomes and improve neurological
      outcomes.

PMID- 29050381
TI  - Space-based bias of covert visual attention in complex regional pain syndrome.
AB  - See Legrain (doi:10.1093/awx188) for a scientific commentary on this article.
      Some patients with complex regional pain syndrome report that movements of the
      affected limb are slow, more effortful, and lack automaticity. These symptoms
      have been likened to the syndrome that sometimes follows brain injury called
      hemispatial neglect, in which patients exhibit attentional impairments and
      problems with movements affecting the contralesional side of the body and space.
      Psychophysical testing of patients with complex regional pain syndrome has found
      evidence for spatial biases when judging visual targets distanced at 2 m, but not
      in directions that indicate reduced attention to the affected side. In contrast,
      when judging visual or tactile stimuli presented on their own body surface, or
      pictures of hands and feet within arm's reach, patients with complex regional
      pain syndrome exhibited a bias away from the affected side. What is not yet known
      is whether patients with complex regional pain syndrome only have biased
      attention for bodily-specific information in the space within arm's reach, or
      whether they also show a bias for information that is not associated with the
      body, suggesting a more generalized attention deficit. Using a temporal order
      judgement task, we found that patients with complex regional pain syndrome
      processed visual stimuli more slowly on the affected side (relative to the
      unaffected side) when the lights were projected onto a blank surface (i.e. when
      no bodily information was visible), and when the lights were projected onto the
      dorsal surfaces of their uncrossed hands. However, with the arms crossed (such
      that the left and right lights projected onto the right and left hands,
      respectively), patients' responses were no different than controls. These results
      provide the first demonstration of a generalized attention bias away from the
      affected side of space in complex regional pain syndrome patients that is not
      specifically related to bodily information. They also suggest a separate and
      additional bias of visual attention away from the affected hand. The strength of
      attention bias was predicted by scores on a self-report measure of body
      perception distortion; but not by pain intensity, time since diagnosis, or
      affected body side (left or right). At an individual level, those patients whose
      upper limbs were most affected had a higher incidence of inattention than those
      whose lower limbs were most affected. However, at a group level, affected limb
      (upper or lower) did not predict bias magnitude; nor did three measures designed
      to assess possible asymmetries in the distribution of movements across space. It
      is concluded that inattention in near space in complex regional pain syndrome may
      arise in parallel with a distorted perception of the
      body.10.1093/brain/awx152_video1awx152media15495542665001.

PMID- 29050382
TI  - Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset
      Alzheimer's disease.
AB  - Patients with Alzheimer's disease can present with different clinical phenotypes.
      Individuals with late-onset Alzheimer's disease (>65 years) typically present
      with medial temporal lobe neurodegeneration and predominantly amnestic
      symptomatology, while patients with early-onset Alzheimer's disease (<65 years)
      exhibit greater neocortical involvement associated with a clinical presentation
      including dyspraxia, executive dysfunction, or visuospatial impairment. We
      recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset
      Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13
      with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy
      elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography
      and structural magnetic resonance imaging to explore whether early- and late
      onset Alzheimer's disease exhibit differential regional tau pathology and atrophy
      patterns. Strong associations of lower age at symptom onset with higher 18F-AV
      1451 uptake were observed in several neocortical regions, while higher age did
      not yield positive associations in neither patient group. Comparing patients with
      early-onset Alzheimer's disease with controls resulted in significantly higher
      18F-AV-1451 retention throughout the neocortex, while comparing healthy controls
      with late-onset Alzheimer's disease patients yielded a distinct pattern of higher
      18F-AV-1451 retention, predominantly confined to temporal lobe regions. When
      compared against each other, the early-onset Alzheimer's disease group exhibited
      greater uptake than the late-onset group in prefrontal and premotor, as well as
      in inferior parietal cortex. These preliminary findings indicate that age may
      constitute an important contributor to Alzheimer's disease heterogeneity
      highlighting the potential of tau positron emission tomography to capture
      phenotypic variation across patients with Alzheimer's disease.

PMID- 29050384
TI  - Stimulating thought: a functional MRI study of transcranial direct current
      stimulation in schizophrenia.
AB  - Individuals with schizophrenia typically suffer a range of cognitive deficits,
      including prominent deficits in working memory and executive function. These
      difficulties are strongly predictive of functional outcomes, but there is a
      paucity of effective therapeutic interventions targeting these deficits.
      Transcranial direct current stimulation is a novel neuromodulatory technique with
      emerging evidence of potential pro-cognitive effects; however, there is limited
      understanding of its mechanism. This was a double-blind randomized sham
      controlled pilot study of transcranial direct current stimulation on a working
      memory (n-back) and executive function (Stroop) task in 28 individuals with
      schizophrenia using functional magnetic resonance imaging. Study participants
      received 30 min of real or sham transcranial direct current stimulation applied
      to the left frontal cortex. The 'real' and 'sham' groups did not differ in online
      working memory task performance, but the transcranial direct current stimulation
      group demonstrated significant improvement in performance at 24 h post
      transcranial direct current stimulation. Transcranial direct current stimulation
      was associated with increased activation in the medial frontal cortex beneath the
      anode; showing a positive correlation with consolidated working memory
      performance 24 h post-stimulation. There was reduced activation in the left
      cerebellum in the transcranial direct current stimulation group, with no change
      in the middle frontal gyrus or parietal cortices. Improved performance on the
      executive function task was associated with reduced activity in the anterior
      cingulate cortex. Transcranial direct current stimulation modulated functional
      activation in local task-related regions, and in more distal nodes in the
      network. Transcranial direct current stimulation offers a potential novel
      approach to altering frontal cortical activity and exerting pro-cognitive effects
      in schizophrenia.

PMID- 29050383
TI  - Early detection of consciousness in patients with acute severe traumatic brain
      injury.
AB  - See Schiff (doi:10.1093/awx209) for a scientific commentary on this article.
      Patients with acute severe traumatic brain injury may recover consciousness
      before self-expression. Without behavioural evidence of consciousness at the
      bedside, clinicians may render an inaccurate prognosis, increasing the likelihood
      of withholding life-sustaining therapies or denying rehabilitative services. Task
      based functional magnetic resonance imaging and electroencephalography techniques
      have revealed covert consciousness in the chronic setting, but these techniques
      have not been tested in the intensive care unit. We prospectively enrolled 16
      patients admitted to the intensive care unit for acute severe traumatic brain
      injury to test two hypotheses: (i) in patients who lack behavioural evidence of
      language expression and comprehension, functional magnetic resonance imaging and
      electroencephalography detect command-following during a motor imagery task (i.e.
      cognitive motor dissociation) and association cortex responses during language
      and music stimuli (i.e. higher-order cortex motor dissociation); and (ii) early
      responses to these paradigms are associated with better 6-month outcomes on the
      Glasgow Outcome Scale-Extended. Patients underwent functional magnetic resonance
      imaging on post-injury Day 9.2 +/- 5.0 and electroencephalography on Day 9.8 +/-
      4.6. At the time of imaging, behavioural evaluation with the Coma Recovery Scale
      Revised indicated coma (n = 2), vegetative state (n = 3), minimally conscious
      state without language (n = 3), minimally conscious state with language (n = 4)
      or post-traumatic confusional state (n = 4). Cognitive motor dissociation was
      identified in four patients, including three whose behavioural diagnosis
      suggested a vegetative state. Higher-order cortex motor dissociation was
      identified in two additional patients. Complete absence of responses to language,
      music and motor imagery was only observed in coma patients. In patients with
      behavioural evidence of language function, responses to language and music were
      more frequently observed than responses to motor imagery (62.5-80% versus 33.3
      42.9%). Similarly, in 16 matched healthy subjects, responses to language and
      music were more frequently observed than responses to motor imagery (87.5-100%
      versus 68.8-75.0%). Except for one patient who died in the intensive care unit,
      all patients with cognitive motor dissociation and higher-order cortex motor
      dissociation recovered beyond a confusional state by 6 months. However, 6-month
      outcomes were not associated with early functional magnetic resonance imaging and
      electroencephalography responses for the entire cohort. These observations
      suggest that functional magnetic resonance imaging and electroencephalography can
      detect command-following and higher-order cortical function in patients with
      acute severe traumatic brain injury. Early detection of covert consciousness and
      cortical responses in the intensive care unit could alter time-sensitive
      decisions about withholding life-sustaining therapies.

PMID- 29050385
TI  - Pope Francis champions Huntington's disease.

PMID- 29050386
TI  - Brain monoamine oxidase B and A in human parkinsonian dopamine deficiency
      disorders.
AB  - See Jellinger (doi:10.1093/awx190) for a scientific commentary on this article.
      The enzyme monoamine oxidases (B and A subtypes, encoded by MAOB and MAOA,
      respectively) are drug targets in the treatment of Parkinson's disease.
      Inhibitors of MAOB are used clinically in Parkinson's disease for symptomatic
      purposes whereas the potential disease-modifying effect of monoamine oxidase
      inhibitors is debated. As astroglial cells express high levels of MAOB, the
      enzyme has been proposed as a brain imaging marker of astrogliosis, a cellular
      process possibly involved in Parkinson's disease pathogenesis as elevation of
      MAOB in astrocytes might be harmful. Since brain monoamine oxidase status in
      Parkinson's disease is uncertain, our objective was to measure, by quantitative
      immunoblotting in autopsied brain homogenates, protein levels of both monoamine
      oxidases in three different degenerative parkinsonian disorders: Parkinson's
      disease (n = 11), multiple system atrophy (n = 11), and progressive supranuclear
      palsy (n = 16) and in matched controls (n = 16). We hypothesized that if MAOB is
      'substantially' localized to astroglial cells, MAOB levels should be generally
      associated with standard astroglial protein measures (e.g. glial fibrillary
      acidic protein). MAOB levels were increased in degenerating putamen (+83%) and
      substantia nigra (+10%, non-significant) in multiple system atrophy; in caudate
      (+26%), putamen (+27%), frontal cortex (+31%) and substantia nigra (+23%) of
      progressive supranuclear palsy; and in frontal cortex (+33%), but not in
      substantia nigra of Parkinson's disease, a region we previously reported no
      increase in astrocyte protein markers. Although the magnitude of MAOB increase
      was less than those of standard astrocytic markers, significant positive
      correlations were observed amongst the astrocyte proteins and MAOB. Despite
      suggestions that MAOA (versus MAOB) is primarily responsible for metabolism of
      dopamine in dopamine neurons, there was no loss of the enzyme in the parkinsonian
      substantia nigra; instead, increased nigral levels of a MAOA fragment and
      'turnover' of the enzyme were observed in the conditions. Our findings provide
      support that MAOB might serve as a biochemical imaging marker, albeit not
      entirely specific, for astrocyte activation in human brain. The observation that
      MAOB protein concentration is generally increased in degenerating brain areas in
      multiple system atrophy (especially putamen) and in progressive supranuclear
      palsy, but not in the nigra in Parkinson's disease, also distinguishes astrocyte
      behaviour in Parkinson's disease from that in the two 'Parkinson-plus'
      conditions. The question remains whether suppression of either MAOB in astrocytes
      or MAOA in dopamine neurons might influence progression of the parkinsonian
      disorders.

PMID- 29050387
TI  - Temporal lobe networks supporting the comprehension of spoken words.
AB  - Auditory word comprehension is a cognitive process that involves the
      transformation of auditory signals into abstract concepts. Traditional lesion
      based studies of stroke survivors with aphasia have suggested that neocortical
      regions adjacent to auditory cortex are primarily responsible for word
      comprehension. However, recent primary progressive aphasia and normal
      neurophysiological studies have challenged this concept, suggesting that the left
      temporal pole is crucial for word comprehension. Due to its vasculature, the
      temporal pole is not commonly completely lesioned in stroke survivors and this
      heterogeneity may have prevented its identification in lesion-based studies of
      auditory comprehension. We aimed to resolve this controversy using a combined
      voxel-based-and structural connectome-lesion symptom mapping approach, since
      cortical dysfunction after stroke can arise from cortical damage or from white
      matter disconnection. Magnetic resonance imaging (T1-weighted and diffusion
      tensor imaging-based structural connectome), auditory word comprehension and
      object recognition tests were obtained from 67 chronic left hemisphere stroke
      survivors. We observed that damage to the inferior temporal gyrus, to the
      fusiform gyrus and to a white matter network including the left posterior
      temporal region and its connections to the middle temporal gyrus, inferior
      temporal gyrus, and cingulate cortex, was associated with word comprehension
      difficulties after factoring out object recognition. These results suggest that
      the posterior lateral and inferior temporal regions are crucial for word
      comprehension, serving as a hub to integrate auditory and conceptual processing.
      Early processing linking auditory words to concepts is situated in posterior
      lateral temporal regions, whereas additional and deeper levels of semantic
      processing likely require more anterior temporal
      regions.10.1093/brain/awx169_video1awx169media15555638084001.

PMID- 29050388
TI  - Patients with Huntington's disease pioneered human stereotactic neurosurgery 70
      years ago.

PMID- 29050391
TI  - Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.
AB  - There are very few case series of patients with acute psychogenic memory loss
      (also known as dissociative/functional amnesia), and still fewer studies of
      outcome, or comparisons with neurological memory-disordered patients.
      Consequently, the literature on psychogenic amnesia is somewhat fragmented and
      offers little prognostic value for individual patients. In the present study, we
      reviewed the case records and neuropsychological findings in 53 psychogenic
      amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively
      recruited neurological memory-disordered patients and 14 healthy control
      subjects. In particular, we examined the pattern of retrograde amnesia on an
      assessment of autobiographical memory (the Autobiographical Memory Interview). We
      found that our patients with psychogenic memory loss fell into four distinct
      groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde
      amnesia; (iii) psychogenic focal retrograde amnesia following a minor
      neurological episode; and (iv) patients with gaps in their memories. While
      neurological cases were characterized by relevant neurological symptoms, a
      history of a past head injury was actually more common in our psychogenic cases
      (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later
      psychological amnesia. As anticipated, loss of the sense of personal identity was
      confined to the psychogenic group. However, clinical depression,
      family/relationship problems, financial/employment problems, and failure to
      recognize the family were also statistically more common in that group. The
      pattern of autobiographical memory loss differed between the psychogenic groups:
      fugue cases showed a severe and uniform loss of memories for both facts and
      events across all time periods, whereas the two focal retrograde amnesia groups
      showed a 'reversed' temporal gradient with relative sparing of recent memories.
      After 3-6 months, the fugue patients had improved to normal scores for facts and
      near-normal scores for events. By contrast, the two focal retrograde amnesia
      groups showed less improvement and continued to show a reversed temporal
      gradient. In conclusion, the outcome in psychogenic amnesia, particularly those
      characterized by fugue, is better than generally supposed. Findings are
      interpreted in terms of Markowitsch's and Kopelman's models of psychogenic
      amnesia, and with respect to Anderson's neuroimaging findings in memory
      inhibition.

PMID- 29050389
TI  - Towards personalized therapy for multiple sclerosis: prediction of individual
      treatment response.
AB  - Timely initiation of effective therapy is crucial for preventing disability in
      multiple sclerosis; however, treatment response varies greatly among patients.
      Comprehensive predictive models of individual treatment response are lacking. Our
      aims were: (i) to develop predictive algorithms for individual treatment response
      using demographic, clinical and paraclinical predictors in patients with multiple
      sclerosis; and (ii) to evaluate accuracy, and internal and external validity of
      these algorithms. This study evaluated 27 demographic, clinical and paraclinical
      predictors of individual response to seven disease-modifying therapies in MSBase,
      a large global cohort study. Treatment response was analysed separately for
      disability progression, disability regression, relapse frequency, conversion to
      secondary progressive disease, change in the cumulative disease burden, and the
      probability of treatment discontinuation. Multivariable survival and generalized
      linear models were used, together with the principal component analysis to reduce
      model dimensionality and prevent overparameterization. Accuracy of the individual
      prediction was tested and its internal validity was evaluated in a separate, non
      overlapping cohort. External validity was evaluated in a geographically distinct
      cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n =
      8513), the most prominent modifiers of treatment response comprised age, disease
      duration, disease course, previous relapse activity, disability, predominant
      relapse phenotype and previous therapy. Importantly, the magnitude and direction
      of the associations varied among therapies and disease outcomes. Higher
      probability of disability progression during treatment with injectable therapies
      was predominantly associated with a greater disability at treatment start and the
      previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly
      associated with lower pretreatment relapse activity. The probability of
      disability regression was predominantly associated with pre-baseline disability,
      therapy and relapse activity. Relapse incidence was associated with pretreatment
      relapse activity, age and relapsing disease course, with the strength of these
      associations varying among therapies. Accuracy and internal validity (n = 1196)
      of the resulting predictive models was high (>80%) for relapse incidence during
      the first year and for disability outcomes, moderate for relapse incidence in
      Years 2-4 and for the change in the cumulative disease burden, and low for
      conversion to secondary progressive disease and treatment discontinuation.
      External validation showed similar results, demonstrating high external validity
      for disability and relapse outcomes, moderate external validity for cumulative
      disease burden and low external validity for conversion to secondary progressive
      disease and treatment discontinuation. We conclude that demographic, clinical and
      paraclinical information helps predict individual response to disease-modifying
      therapies at the time of their commencement.

PMID- 29050390
TI  - Involvement of fast-spiking cells in ictal sequences during spontaneous seizures
      in rats with chronic temporal lobe epilepsy.
AB  - See Lenck-Santini (doi:10.1093/awx205) for a scientific commentary on this
      article. Epileptic seizures represent altered neuronal network dynamics, but the
      temporal evolution and cellular substrates of the neuronal activity patterns
      associated with spontaneous seizures are not fully understood. We used
      simultaneous recordings from multiple neurons in the hippocampus and neocortex of
      rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells
      discharge in a highly stereotypical sequential pattern during ictal events, and
      that these stereotypical patterns were reproducible across consecutive seizures.
      In contrast to the canonical view that principal cell discharges dominate ictal
      events, the ictal sequences were predominantly composed of fast-spiking, putative
      inhibitory neurons, which displayed unusually strong coupling to local field
      potential even before seizures. The temporal evolution of activity was
      characterized by unique dynamics where the most correlated neuronal pairs before
      seizure onset displayed the largest increases in correlation strength during the
      seizures. These results demonstrate the selective involvement of fast spiking
      interneurons in structured temporal sequences during spontaneous ictal events in
      hippocampal and neocortical circuits in experimental models of chronic temporal
      lobe epilepsy.

PMID- 29050393
TI  - Distinct processing of ambiguous speech in people with non-clinical auditory
      verbal hallucinations.
AB  - Auditory verbal hallucinations (hearing voices) are typically associated with
      psychosis, but a minority of the general population also experience them
      frequently and without distress. Such 'non-clinical' experiences offer a rare and
      unique opportunity to study hallucinations apart from confounding clinical
      factors, thus allowing for the identification of symptom-specific mechanisms.
      Recent theories propose that hallucinations result from an imbalance of prior
      expectation and sensory information, but whether such an imbalance also
      influences auditory-perceptual processes remains unknown. We examine for the
      first time the cortical processing of ambiguous speech in people without
      psychosis who regularly hear voices. Twelve non-clinical voice-hearers and 17
      matched controls completed a functional magnetic resonance imaging scan while
      passively listening to degraded speech ('sine-wave' speech), that was either
      potentially intelligible or unintelligible. Voice-hearers reported recognizing
      the presence of speech in the stimuli before controls, and before being
      explicitly informed of its intelligibility. Across both groups, intelligible sine
      wave speech engaged a typical left-lateralized speech processing network.
      Notably, however, voice-hearers showed stronger intelligibility responses than
      controls in the dorsal anterior cingulate cortex and in the superior frontal
      gyrus. This suggests an enhanced involvement of attention and sensorimotor
      processes, selectively when speech was potentially intelligible. Altogether,
      these behavioural and neural findings indicate that people with hallucinatory
      experiences show distinct responses to meaningful auditory stimuli. A greater
      weighting towards prior knowledge and expectation might cause non-veridical
      auditory sensations in these individuals, but it might also spontaneously
      facilitate perceptual processing where such knowledge is required. This has
      implications for the understanding of hallucinations in clinical and non-clinical
      populations, and is consistent with current 'predictive processing' theories of
      psychosis.

PMID- 29050392
TI  - Clinical spectrum and genotype-phenotype associations of KCNA2-related
      encephalopathies.
AB  - Recently, de novo mutations in the gene KCNA2, causing either a dominant-negative
      loss-of-function or a gain-of-function of the voltage-gated K+ channel Kv1.2,
      were described to cause a new molecular entity within the epileptic
      encephalopathies. Here, we report a cohort of 23 patients (eight previously
      described) with epileptic encephalopathy carrying either novel or known KCNA2
      mutations, with the aim to detail the clinical phenotype associated with each of
      them, to characterize the functional effects of the newly identified mutations,
      and to assess genotype-phenotype associations. We identified five novel and
      confirmed six known mutations, three of which recurred in three, five and seven
      patients, respectively. Ten mutations were missense and one was a truncation
      mutation; de novo occurrence could be shown in 20 patients. Functional studies
      using a Xenopus oocyte two-microelectrode voltage clamp system revealed mutations
      with only loss-of-function effects (mostly dominant-negative current amplitude
      reduction) in eight patients or only gain-of-function effects (hyperpolarizing
      shift of voltage-dependent activation, increased amplitude) in nine patients. In
      six patients, the gain-of-function was diminished by an additional loss-of
      function (gain-and loss-of-function) due to a hyperpolarizing shift of voltage
      dependent activation combined with either decreased amplitudes or an additional
      hyperpolarizing shift of the inactivation curve. These electrophysiological
      findings correlated with distinct phenotypic features. The main differences were
      (i) predominant focal (loss-of-function) versus generalized (gain-of-function)
      seizures and corresponding epileptic discharges with prominent sleep activation
      in most cases with loss-of-function mutations; (ii) more severe epilepsy,
      developmental problems and ataxia, and atrophy of the cerebellum or even the
      whole brain in about half of the patients with gain-of-function mutations; and
      (iii) most severe early-onset phenotypes, occasionally with neonatal onset
      epilepsy and developmental impairment, as well as generalized and focal seizures
      and EEG abnormalities for patients with gain- and loss-of-function mutations. Our
      study thus indicates well represented genotype-phenotype associations between
      three subgroups of patients with KCNA2 encephalopathy according to the
      electrophysiological features of the mutations.

PMID- 29050395
TI  - Lost in space: do somatic symptoms affect the perception of extra-somatic
      stimuli?

PMID- 29050394
TI  - Cortical neurons and networks are dormant but fully responsive during isoelectric
      brain state.
AB  - A continuous isoelectric electroencephalogram reflects an interruption of
      endogenously-generated activity in cortical networks and systematically results
      in a complete dissolution of conscious processes. This electro-cerebral
      inactivity occurs during various brain disorders, including hypothermia, drug
      intoxication, long-lasting anoxia and brain trauma. It can also be induced in a
      therapeutic context, following the administration of high doses of barbiturate
      derived compounds, to interrupt a hyper-refractory status epilepticus. Although
      altered sensory responses can be occasionally observed on an isoelectric
      electroencephalogram, the electrical membrane properties and synaptic responses
      of individual neurons during this cerebral state remain largely unknown. The aim
      of the present study was to characterize the intracellular correlates of a
      barbiturate-induced isoelectric electroencephalogram and to analyse the sensory
      evoked synaptic responses that can emerge from a brain deprived of spontaneous
      electrical activity. We first examined the sensory responsiveness from patients
      suffering from intractable status epilepticus and treated by administration of
      thiopental. Multimodal sensory responses could be evoked on the flat
      electroencephalogram, including visually-evoked potentials that were
      significantly amplified and delayed, with a high trial-to-trial reproducibility
      compared to awake healthy subjects. Using an analogous pharmacological procedure
      to induce prolonged electro-cerebral inactivity in the rat, we could describe its
      cortical and subcortical intracellular counterparts. Neocortical, hippocampal and
      thalamo-cortical neurons were all silent during the isoelectric state and
      displayed a flat membrane potential significantly hyperpolarized compared with
      spontaneously active control states. Nonetheless, all recorded neurons could fire
      action potentials in response to intracellularly injected depolarizing current
      pulses and their specific intrinsic electrophysiological features were preserved.
      Manipulations of the membrane potential and intracellular injection of chloride
      in neocortical neurons failed to reveal an augmented synaptic inhibition during
      the isoelectric condition. Consistent with the sensory responses recorded from
      comatose patients, large and highly reproducible somatosensory-evoked potentials
      could be generated on the inactive electrocorticogram in rats. Intracellular
      recordings revealed that the underlying neocortical pyramidal cells responded to
      sensory stimuli by complex synaptic potentials able to trigger action potentials.
      As in patients, sensory responses in the isoelectric state were delayed compared
      to control responses and exhibited an elevated reliability during repeated
      stimuli. Our findings demonstrate that during prolonged isoelectric brain state
      neurons and synaptic networks are dormant rather than excessively inhibited,
      conserving their intrinsic properties and their ability to integrate and
      propagate environmental stimuli.

PMID- 29050396
TI  - Brain monoamine oxidases in human parkinsonian disorders.

PMID- 29050397
TI  - The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double
      blind randomized study.
AB  - Mexiletine is the only drug with proven effect for treatment of non-dystrophic
      myotonia, but mexiletine is expensive, has limited availability and several side
      effects. There is therefore a need to identify other pharmacological compounds
      that can alleviate myotonia in non-dystrophic myotonias. Like mexiletine,
      lamotrigine is a sodium channel blocker, but unlike mexiletine, lamotrigine is
      available, inexpensive, and well tolerated. We investigated the potential of
      using lamotrigine for treatment of myotonia in patients with non-dystrophic
      myotonias. In this, randomized double-blind, placebo-controlled, two-period cross
      over study, we included adult outpatients recruited from all of Denmark with
      clinical myotonia and genetically confirmed myotonia congenita and paramyotonia
      congenita for investigation at the Copenhagen Neuromuscular Center. A pharmacy
      produced the medication and placebo, and randomized patients in blocks of 10.
      Participants and investigators were all blinded to treatment until the end of the
      trial. In two 8-week periods, oral lamotrigine or placebo capsules were provided
      once daily, with increasing doses (from 25 mg, 50 mg, 150 mg to 300 mg) every
      second week. The primary outcome was a severity score of myotonia, the Myotonic
      Behaviour Scale ranging from asymptomatic (score 1) to invalidating myotonia
      (score 6), reported by the participants during Weeks 0 and 8 in each treatment
      period. Clinical myotonia was also measured and side effects were monitored. The
      study was registered at ClinicalTrials.gov (NCT02159963) and EudraCT (2013-003309
      24). We included 26 patients (10 females, 16 males, age: 19-74 years) from 13
      November 2013 to 6 July 2015. Twenty-two completed the entire study. One patient
      withdrew due to an allergic reaction to lamotrigine. Three patients withdrew for
      reasons not related to the trial intervention. The Myotonic Behaviour Scale at
      baseline was 3.2 +/- 1.1, which changed after treatment with lamotrigine by 1.3
      +/- 0.2 scores (P < 0.001), but not with placebo (0.2 +/- 0.1 scores, P = 0.4).
      The estimated effect size was 1.0 +/- 0.2 (95% confidence interval = 0.5-1.5, P <
      0.001, n = 22). The standardized effect size of lamotrigine was 1.5 (confidence
      interval: 1.2-1.8). Number needed to treat was 2.6 (P = 0.006, n = 26). No
      adverse or unsuspected event occurred. Common side effects occurred in both
      treatment groups; number needed to harm was 5.2 (P = 0.11, n = 26). Lamotrigine
      effectively reduced myotonia, emphasized by consistency between effects on
      patient-related outcomes and objective outcomes. The frequency of side effects
      was acceptable. Considering this and the high availability and low cost of the
      drug, we suggest that lamotrigine should be used as the first line of treatment
      for myotonia in treatment-naive patients with non-dystrophic myotonias.

PMID- 29050399
TI  - Diagnostic criteria for chronic lymphocytic inflammation with pontine
      perivascular enhancement responsive to steroids (CLIPPERS).
AB  - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
      to steroids (CLIPPERS) is a central nervous system inflammatory syndrome
      predominantly affecting the brainstem, cerebellum, and spinal cord. Following its
      initial description, the salient features of CLIPPERS have been confirmed and
      expanded upon, but the lack of formalized diagnostic criteria has led to reports
      of patients with dissimilar features purported to have CLIPPERS. We evaluated
      clinical, radiological and pathological features of patients referred for
      suspected CLIPPERS and propose diagnostic criteria to discriminate CLIPPERS from
      non-CLIPPERS aetiologies. Thirty-five patients were evaluated for suspected
      CLIPPERS. Clinical and neuroimaging data were reviewed by three neurologists to
      confirm CLIPPERS by consensus agreement. Neuroimaging and neuropathology were
      reviewed by experienced neuroradiologists and neuropathologists, respectively,
      both of whom were blinded to the clinical data. CLIPPERS was diagnosed in 23
      patients (18 male and five female) and 12 patients had a non-CLIPPERS diagnosis.
      CLIPPERS patients' median age of onset was 58 years (interquartile range, 24-72)
      and were followed a median of 44 months (interquartile range 38-63). Non-CLIPPERS
      patients' median age of onset was 52 years (interquartile range, 39-59) and were
      followed a median of 27 months (interquartile range, 14-47). Clinical symptoms of
      gait ataxia, diplopia, cognitive impairment, and facial paraesthesia did not
      discriminate CLIPPERS from non-CLIPPERS. Marked clinical and radiological
      corticosteroid responsiveness was observed in CLIPPERS (23/23), and clinical
      worsening occurred in all 12 CLIPPERS cases when corticosteroids were
      discontinued. Corticosteroid responsiveness was common but not universal in non
      CLIPPERS [clinical improvement (8/12); radiological improvement (2/12); clinical
      worsening on discontinuation (3/8)]. CLIPPERS patients had brainstem predominant
      perivascular gadolinium enhancing lesions on magnetic resonance imaging that were
      discriminated from non-CLIPPERS by: homogenous gadolinium enhancing nodules <3 mm
      in diameter without ring-enhancement or mass effect, and homogenous T2 signal
      abnormality not significantly exceeding the T1 enhancement. Brain neuropathology
      on 14 CLIPPERS cases demonstrated marked CD3-positive T-lymphocyte, mild B
      lymphocyte and moderate macrophage infiltrates, with perivascular predominance as
      well as diffuse parenchymal infiltration (14/14), present in meninges, white and
      grey matter, associated with variable tissue destruction, astrogliosis and
      secondary myelin loss. Clinical, radiological and pathological feature define
      CLIPPERS syndrome and are differentiated from non-CLIPPERS aetiologies by
      neuroradiological and neuropathological findings.

PMID- 29050401
TI  - Stereotypical activation of hippocampal ensembles during seizures.

PMID- 29050398
TI  - Delineating SPTAN1 associated phenotypes: from isolated epilepsy to
      encephalopathy with progressive brain atrophy.
AB  - De novo in-frame deletions and duplications in the SPTAN1 gene, encoding the non
      erythrocyte alphaII spectrin, have been associated with severe West syndrome with
      hypomyelination and pontocerebellar atrophy. We aimed at comprehensively
      delineating the phenotypic spectrum associated with SPTAN1 mutations. Using
      different molecular genetic techniques, we identified 20 patients with a
      pathogenic or likely pathogenic SPTAN1 variant and reviewed their clinical,
      genetic and imaging data. SPTAN1 de novo alterations included seven unique
      missense variants and nine in-frame deletions/duplications of which 12 were
      novel. The recurrent three-amino acid duplication p.(Asp2303_Leu2305dup) occurred
      in five patients. Our patient cohort exhibited a broad spectrum of
      neurodevelopmental phenotypes, comprising six patients with mild to moderate
      intellectual disability, with or without epilepsy and behavioural disorders, and
      14 patients with infantile epileptic encephalopathy, of which 13 had severe
      neurodevelopmental impairment and four died in early childhood. Imaging studies
      suggested that the severity of neurological impairment and epilepsy correlates
      with that of structural abnormalities as well as the mutation type and location.
      Out of seven patients harbouring mutations outside the alpha/beta spectrin
      heterodimerization domain, four had normal brain imaging and three exhibited
      moderately progressive brain and/or cerebellar atrophy. Twelve of 13 patients
      with mutations located within the spectrin heterodimer contact site exhibited
      severe and progressive brain, brainstem and cerebellar atrophy, with
      hypomyelination in most. We used fibroblasts from five patients to study spectrin
      aggregate formation by Triton-X extraction and immunocytochemistry followed by
      fluorescence microscopy. alphaII/betaII aggregates and alphaII spectrin in the
      insoluble protein fraction were observed in fibroblasts derived from patients
      with the mutations p.(Glu2207del), p.(Asp2303_Leu2305dup) and
      p.(Arg2308_Met2309dup), all falling in the nucleation site of the alpha/beta
      spectrin heterodimer region. Molecular modelling of the seven SPTAN1 amino acid
      changes provided preliminary evidence for structural alterations of the A-, B-
      and/or C-helices within each of the mutated spectrin repeats. We conclude that
      SPTAN1-related disorders comprise a wide spectrum of neurodevelopmental
      phenotypes ranging from mild to severe and progressive. Spectrin aggregate
      formation in fibroblasts with mutations in the alpha/beta heterodimerization
      domain seems to be associated with a severe neurodegenerative course and suggests
      that the amino acid stretch from Asp2303 to Met2309 in the alpha20 repeat is
      important for alpha/beta spectrin heterodimer formation and/or alphaII spectrin
      function.

PMID- 29050400
TI  - Metformin reverses TRAP1 mutation-associated alterations in mitochondrial
      function in Parkinson's disease.
AB  - The mitochondrial proteins TRAP1 and HTRA2 have previously been shown to be
      phosphorylated in the presence of the Parkinson's disease kinase PINK1 but the
      downstream signalling is unknown. HTRA2 and PINK1 loss of function causes
      parkinsonism in humans and animals. Here, we identified TRAP1 as an interactor of
      HTRA2 using an unbiased mass spectrometry approach. In our human cell models,
      TRAP1 overexpression is protective, rescuing HTRA2 and PINK1-associated
      mitochondrial dysfunction and suggesting that TRAP1 acts downstream of HTRA2 and
      PINK1. HTRA2 regulates TRAP1 protein levels, but TRAP1 is not a direct target of
      HTRA2 protease activity. Following genetic screening of Parkinson's disease
      patients and healthy controls, we also report the first TRAP1 mutation leading to
      complete loss of functional protein in a patient with late onset Parkinson's
      disease. Analysis of fibroblasts derived from the patient reveal that oxygen
      consumption, ATP output and reactive oxygen species are increased compared to
      healthy individuals. This is coupled with an increased pool of free NADH,
      increased mitochondrial biogenesis, triggering of the mitochondrial unfolded
      protein response, loss of mitochondrial membrane potential and sensitivity to
      mitochondrial removal and apoptosis. These data highlight the role of TRAP1 in
      the regulation of energy metabolism and mitochondrial quality control.
      Interestingly, the diabetes drug metformin reverses mutation-associated
      alterations on energy metabolism, mitochondrial biogenesis and restores
      mitochondrial membrane potential. In summary, our data show that TRAP1 acts
      downstream of PINK1 and HTRA2 for mitochondrial fine tuning, whereas TRAP1 loss
      of function leads to reduced control of energy metabolism, ultimately impacting
      mitochondrial membrane potential. These findings offer new insight into
      mitochondrial pathologies in Parkinson's disease and provide new prospects for
      targeted therapies.

PMID- 29050402
TI  - Uncovering hidden integrative cerebral function in the intensive care unit.

PMID- 29050403
TI  - Editorial.

PMID- 29050404
TI  - The evolution of consciousness. Together with a diagram illustrating certain
      homologies in the nervous system. By W.H.B. Stoddart MD MRCP. Brain 1903; 26: 432
      439. With The structure of consciousness by Michael Polanyi. Brain 1965; 88: 799
      810.

PMID- 29050405
TI  - Comparative effects of in ovo versus subcutaneous administration of the Marek's
      disease vaccine and pre-placement holding time on the processing yield of Ross
      708 broilers.
AB  - Effects of the in ovo (i.o.) or subcutaneous (s.c.) method of administration
      (moa) of the Marek's disease (MD) vaccine and 4 or 18 h pre-placement holding
      time (pht) on the processing yield of male broilers through 49 d of age (doa)
      were investigated. Ross 708 broiler hatching eggs (3,900) were either i.o.
      vaccinated at 18 d of incubation or chicks from eggs that were not i.o.
      vaccinated were s.c.-vaccinated at hatch. The i.o. injections (50 MUL) were
      delivered by a commercial multi-egg injector and s.c. injections (200 MUL) were
      delivered by an automatic pneumatic s.c. injector. The pht was imposed on chicks
      after vaccination. Sixteen birds were initially assigned to each of 15 replicate
      floor pens belonging to each of the moa and pht combination groups and were grown
      out through 48 doa. At 48 doa, 6 birds were randomly selected from each replicate
      pen and were weighed and fasted for 16 h before being processed. At 49 doa, whole
      carcass, fat pad, breast muscle, and tenders muscles weights were recorded. Whole
      carcass weight as a percentage of live BW, and fat pad, breast muscle, and
      tenders muscles weights as percentages of both live and whole carcass weights
      were calculated. Upon subjection of the data to a 2 * 2 factorial analysis, only
      a main effect due to moa was observed for tenders muscles weight as a percentage
      of live and whole carcass weights. Tenders muscles weight as a percentage of both
      live (P <= 0.010) and whole carcass (P <= 0.004) weight was higher in birds
      hatched from eggs that received i.o. rather than s.c. vaccinations. In
      conclusion, in comparison to s.c. vaccination, i.o. vaccination increased
      relative tenders weight yield, whether or not broilers were held for 4 or 18 h
      prior to placement. Therefore, with regard to broiler processing yield, i.o. and
      s.c. vaccinations were safe for the administration of the MD vaccine, with i.o.
      vaccination displaying a slight potential advantage.

PMID- 29050406
TI  - Microbiological quality assessment and validation of antimicrobials against
      unstressed or cold-stress adapted Salmonella and surrogate Enterococcus faecium
      on broiler carcasses and wings.
AB  - This study aims to evaluate the microbiological quality and efficacy of
      antimicrobials to inactivate unstressed or cold-stress adapted Salmonella and
      Enterococcus on broiler carcasses and wings processed at a small USDA-inspected
      slaughter facility in West Virginia. The first part of the study included 42
      carcasses that were pre- and secondarily-enriched in bacterial media followed by
      streak-plating onto XLT-4 and HardyCHROMTM-agar Salmonella and confirmation using
      an API20E-kit. The aerobic plate counts (APC), Escherichia coli (ECC), total
      coliforms (TCC), and yeast/molds were analyzed on petri-films. The second part of
      the study included fresh broiler carcasses and wings that were inoculated with
      unstressed and cold-stress-adapted (4  degrees C, 7-day) Salmonella Typhimurium
      and Tennessee, and Enterococcus faecium ATCC 8459 (5.5 to 6.0 log10CFU/mL) and
      later dipped into peroxyacetic acid (PAA; 1,000 ppm), lactic acid (LA; 5%),
      lactic and citric acid blend (LCA; 2.5%), and sodium hypochlorite (SH; 70 ppm)
      for 30 s without (carcasses) or with 2-min drainage (wings). The surviving
      bacteria were recovered onto non-selective and selective agar to analyze the
      total microbial population, Salmonella and Enterococcus. APC, TCC, and
      Yeast/Molds were 2.62, 1.08, and 2.37 log10CFU/mL on broiler carcasses,
      respectively. A total of 30 and 40% of the carcasses tested positive for
      Salmonella spp. and E. coli (0.48 to 1.70 log10CFU/mL), respectively. For
      carcasses, antimicrobial reductions of cold-stress-adapted cells of Salmonella
      and Enterococcus were greater (P < 0.05) than the unstressed cells. For wings,
      cold-stress-adapted Salmonella were more (P < 0.05) sensitive to antimicrobials
      than unstressed cells; however, unstressed and cold-stress-adapted Enterococcus
      behaved similarly (P > 0.05). The reduction of Salmonella and Enterococcus on
      carcasses and wings increased in the order of SH <= LCA < LA < PAA and
      irrespective of unstressed or cold-stress-adapted cells. Applying post-chilling
      antimicrobial dipping treatments could be an intervention approach to control
      Salmonella on locally processed broilers. In addition, Enterococcus faecium could
      be a Salmonella surrogate for in-plant validation studies.

PMID- 29050407
TI  - Layer chicken embryo survival to hatch when administered an in ovo vaccination of
      strain F Mycoplasma gallisepticum and locations of bacteria prevalence in the
      newly hatched chick.
AB  - Mycoplasma gallisepticum (MG) is a bacterial pathogen that causes production
      losses in layer chickens. To combat MG, multiage layer facilities vaccinate
      pullets by either spray or eye-drop vaccination. The objective in this study was
      to evaluate the use of in ovo vaccination as a potential alternative for MG
      vaccination. Layer embryos at 18 d of incubation were either not-injected
      (control), or were hand-injected with either commercial Marek's disease vaccine
      diluent alone or with a high, medium, low, or very low dosage of a live
      attenuated strain F (FMG) vaccine suspended in the commercial diluent. Hatch
      success and residual egg embryonic mortality were determined after 23 d of
      incubation. Six hatched chicks per treatment were swabbed for the detection of
      FMG at 4 different sites (trachea, mouth and esophagus, yolk sac membrane, and
      the lumen of the duodenal loop) via real-time PCR. Embryos were found to be
      administered 106 CFU per dose in the high treatment, 104 CFU/dose in the medium
      treatment, 102 CFU/dose in the low treatment, and between 5.06 and 5.93 CFU/dose
      in the very low treatment. Hatch of embryonated eggs was decreased by the medium
      and high doses (P = 0.02). These embryos died while pipping. No FMG was detected
      in the control and diluent-injected chicks. In the FMG treatments, FMG was found
      in all sites and dosages, with a greater number of positive chicks found in the
      higher FMG dosage treatments. These findings indicate the potential practicality
      of vaccinating layer embryos with FMG by in ovo injection based on the observed
      hatch success at lower dosages. Also, once injected into the amnion, the bacteria
      are present in the upper respiratory and gastrointestinal tracts as well the yolk
      sac membrane and the small intestine of hatchlings. Future research will need to
      ascertain the effects of FMG administered by in ovo injection on posthatch
      immunity and mortality.

PMID- 29050408
TI  - Effect of space allowance and cage size on laying hens housed in furnished cages,
      Part I: Performance and well-being.
AB  - There are few published data on the effects of housing laying hens at different
      densities in large furnished cages (FC; a.k.a. enriched colony cages). The
      objective of this study was to determine the effects of housing laying hens at 2
      space allowances (SA) in 2 sizes of FC on measures of production and well-being.
      At 18 wk of age, 1,218 LSL-Lite hens were housed in cages furnished with a
      curtained nesting area, perches, and scratch mat, and stocked at either 520 cm2
      (Low) or 748 cm2 (High) total floor space. This resulted in 4 group sizes: 40 vs.
      28 birds in smaller FC (SFC) and 80 vs. 55 in larger FC (LFC). Data were
      collected from 20 to 72 wks of age. There was no effect of cage size (P = 0.21)
      or SA (P = 0.37) on hen day egg production, egg weight (PSize = 0.90; PSA =
      0.73), or eggshell deformation (PSize = 0.14; PSA = 0.053), but feed
      disappearance was higher in SFC than LFC (P = 0.005). Mortality to 72 wk was not
      affected by cage size (P = 0.78) or SA (P = 0.55). BW (P = 0.006) and BW CV (P =
      0.008) increased with age but were not affected by treatment. Feather cleanliness
      was poorer in FC with low SA vs. high (P < 0.0001) and small vs. large FC (P <
      0.0001). Feather condition was poorer in low SA (P = 0.048) and the best in small
      cages with high SA (P = 0.006), but deteriorated in all treatments over time (P <
      0.0001). Treatments did not affect the breaking strengths of femur, tibia, or
      humerus, proportions of birds suffering keel deformations, or foot health scores.
      Overall, the SA studied in the 2 cage sizes in this trial had few effects on
      production parameters. However, stocking birds at the lower space allowance
      resulted in some measures of poorer external condition in both sizes of FC, which
      indicates that the welfare of hens housed at the lower space allowance may be
      compromised according to some welfare assessment criteria.

PMID- 29050409
TI  - The effect of space allowance and cage size on laying hens housed in furnished
      cages, Part II: Behavior at the feeder.
AB  - Standards for feeder (a.k.a. feed trough) space allowance (SA) are based
      primarily on studies in conventional cages where laying hens tend to eat
      simultaneously, limiting feeder space. Large furnished cages (FC) offer more
      total space and opportunities to perform a greater variety of behaviors, which
      may affect feeding behavior and feeder space requirements. Our objective was to
      determine the effects of floor/feeder SA on behavior at the feeder. LSL-Lite hens
      were housed in FC equipped with a nest, perches, and a scratch mat. Hens with SA
      of either 520 cm2 (Low; 8.9 cm feeder space/hen) or 748 cm2 (High; 12.8 cm feeder
      space/hen) per bird resulted in groups of 40 vs. 28 birds in small FC (SFC) and
      80 vs. 55 in large FC (LFC). Chain feeders ran at 0500, 0800, 1100, 1400, and
      1700 with lights on at 0500 and off at 1900 hours. Digital recordings of FC were
      scanned at chain feeder onset and every 15 min for one h after (5 scans * 5
      feeding times * 2 d) to count the number of birds with their head in the feeder.
      All occurrences of aggressive pecks and displacements during 2 continuous 30
      minute observations at 0800 h and 1700 h also were counted. Mixed model repeated
      analyses tested the effects of SA, cage size, and time on the percent of hens
      feeding, and the frequency of aggressive pecks and displacements. Surprisingly,
      the percent of birds feeding simultaneously was similar regardless of cage size
      (LFC: 23.0 +/- 0.9%; SFC: 24.0 +/- 1.0%; P = 0.44) or SA (Low: 23.8 +/- 0.9%;
      High: 23.3 +/- 1.0%; P = 0.62). More birds were observed feeding at 1700 h (35.3
      +/- 0.1%) than any at other time (P < 0.001). Feeder use differed by cage area
      (nest, middle, or scratch) over the d (P < 0.001). The frequency of aggressive
      pecks was low overall and not affected by SA or cage size. Frequency of
      displacements was also low but greater at Low SA (P = 0.001). There was little
      evidence of feeder competition at the Low SA in this study.

PMID- 29050410
TI  - Effect of feeding soybean meal and differently processed peas on intestinal
      morphology and functional glucose transport in the small intestine of broilers.
AB  - Peas are locally grown legumes being rich in protein and starch. However, the
      broad usage of peas as a feed component in poultry nutrition is limited to anti
      nutritional factors, which might impair gut morphology and function. This study
      investigated the effect of feeding raw or differently processed peas compared
      with feeding a soybean meal-based control diet (C) on intestinal morphology and
      nutrient transport in broilers. A total of 360 day-old broiler chicks were fed
      with one of the following diets: The C diet, and 3 diets containing raw peas
      (RP), fermented peas (FP) and enzymatically pre-digested peas (EP), each
      supplying 30% of dietary crude protein. After 35 d, jejunal samples of broilers
      were taken for analyzing histomorphological parameters, active glucose transport
      in Ussing chambers and the expression of genes related to glucose absorption,
      intestinal permeability and cell maturation. Villus length (P = 0.017) and crypt
      depth (P = 0.009) of EP-fed broilers were shorter compared to birds received C.
      The villus surface area was larger in broilers fed C compared to those fed with
      the pea-containing feed (P = 0.005). Glucose transport was higher for broilers
      fed C in comparison to birds fed with the EP diet (P = 0.044). The sodium
      dependent glucose co-transporter 1 (SGLT-1) expression was down-regulated in RP
      (P = 0.028) and FP (P = 0.015) fed broilers. Correlation analyses show that
      jejunal villus length negatively correlates with the previously published number
      of jejunal intraepithelial T cells (P = 0.014) and that jejunal glucose transport
      was negatively correlated with the occurrence of jejunal intraepithelial
      leukocytes (P = 0.041). To conclude, the feeding of raw and processed pea
      containing diets compared to a soybean based diet reduced the jejunal mucosal
      surface area of broilers, which on average was accompanied by lower glucose
      transport capacities. These morphological and functional alterations were
      associated with observed mucosal immune reactions. Further studies are required
      elucidating the specific components in peas provoking such effects and whether
      these effects have a beneficial or detrimental impact on gut function and animal
      health.

PMID- 29050411
TI  - Incubation temperature and time of hatch impact broiler muscle growth and
      morphology.
AB  - The adult myogenic population of stem cells, called satellite cells, initially
      develop in late-term embryos. Satellite cells are the only myogenic cell that
      repair damaged myofibers and increase post-hatch growth. The objective of the
      current study was to determine if incubation temperatures and time of hatch
      impact growth and pectoralis major (p. major) muscle morphology. Eggs were
      incubated at a constant 37.8 degrees C; however, from d 14 to 18, the eggs were
      subject to 39.5 degrees C for 0, 3, or 12 h per day. Chicks were divided into
      early, mid, or late hatch groups based upon the time they emerged from the shell.
      Growth and feed efficiency were measured throughout the 63-day trial, while meat
      quality and muscle morphology were evaluated at the time of processing. The
      chicks incubated at an increased temperature for 12 h per d had reduced (P <
      0.01) body weights throughout the trial compared to the 3 h treatment and
      control. The early hatch broilers were heavier (P < 0.01) at 63 d compared to mid
      and late hatch broilers. Chicks from the 12 h incubation treatment had an
      increased (P = 0.01) gain to feed ratio compared to the control. Broilers from
      the 12 h incubation treatment had lower (P < 0.01) p. major weights compared to
      the 0 and 3 h treatments. Early hatch broilers had heavier p. major weights (P <
      0.01) compared to mid and late hatch groups. The 12 h incubation treatment also
      reduced the number of broilers with moderate to severe myopathic attributes
      compared to the control. Similarly, there were fewer late hatch birds with
      fibrotic and necrotic p. major muscles compared to the early hatch group.
      Together, these data demonstrate that altering incubation temperature is a
      feasible management strategy to improve muscle morphology without negatively
      impacting meat quality parameters.

PMID- 29050412
TI  - Adaptive response to exercise of fast-growing and slow-growing chicken strains:
      Blood oxidative status and non-enzymatic antioxidant defense.
AB  - The adaptation of chickens to free-range rearing systems mainly involves the
      locomotory behavior, which is very different in fast-growing (FG) and slow
      growing (SG) strains. This study aimed to compare the effect of moderate
      locomotory activity (induced and prolonged) on the blood oxidative status in a
      slow-growing chicken strain with that in a fast-growing one. Thirty FG (Ross 308)
      birds and 30 SG (Hubbard) birds were divided into 2 groups for each strain and
      subjected to different treatments: no exercise (the control group [C]) and 1 h of
      walking at 4 km/h (the exercise group [E]). Daily exercise was promoted by
      operators, who walked behind the animals around a paddock. Blood samples were
      obtained weekly from both groups. For the E group, samples were obtained before
      exercise (E1) and after exercise (E2). Oxidative markers (creatine kinase [CK],
      reactive oxygen molecular substance [ROMS], thiobarbituric acid reactive
      substances [TBARS]), and antioxidant compounds (alpha-tocopherol [alpha-T], gamma
      tocopherol [gamma-T], delta-tocopherol [delta-T], alpha-tocotrienol [alpha-T3],
      gamma-tocotrienol [gamma-T3], retinol, and carotenoids) were evaluated. In both
      strains, the CK level was higher in chickens subjected to exercise; however, its
      increase was greater in the FG group than in the SG one (1.56-fold vs. 1.08
      fold). The antioxidant status was worse in FG strain birds subjected to exercise,
      whereas the status remained nearly the same in the SG strain birds. The alpha-T
      and retinol concentrations were significantly reduced by exercise, primarily in
      the FG group, whereas the other antioxidant compounds (alpha-T3, gamma-T3, gamma
      T, delta-T, lutein, and zeaxanthin) were unaffected by strain or treatment. The
      FG and SG strains had different responses to exercise, and only the SG showed a
      progressive reduction in TBARS and ROMS values during the 28-day experiment.
      Accordingly, moderate exercise may be beneficial only when the birds have
      suitable behavioral characteristics (e.g., higher kinetic activity, rusticity,
      and explorative nature) or physical characteristics (e.g., low body weight);
      otherwise, exercise is highly stressful and affects physiology and well-being.

PMID- 29050413
TI  - Laying hens in aviaries with different litter substrates: Behavior across the
      flock cycle and feather lipid content.
AB  - The tiered aviary for laying hens includes a floor litter area to promote
      foraging and dust bathing. Data are needed on hens' use of different litter
      substrates and effectiveness of substrates in removing excess feather lipids to
      ensure a suitable litter area. Bovans White hens were housed in commercial-style
      aviaries with access to one of 3 litter substrates (wood shavings, straw, or
      plastic turf mats-AstroTurf(r), n = 4 aviary pens per substrate, 144 cage-reared
      hens populated per pen). Litter areas were videoed across 2 d each at 4 ages:
      immediately following first aviary opening (25 wk), then at 28, 50, and 68 weeks.
      Observations of hens throughout the d included percentages of all hens in each
      pen on the litter area, foraging and transitioning between the tiered enclosure
      and litter area. Percentages of hens dust bathing were observed from 11:00 to
      15:00. Breast and back feather samples from 7 birds per pen at 28, 50, and 68 wk
      were analyzed for lipid content. Overall, fewer hens simultaneously accessed the
      AstroTurf(r) (P < 0.0001), but flocks showed relatively balanced transitions
      between the tiered enclosure and the litter area throughout the d, regardless of
      substrate. On average, less than 5% of all hens were observed dust bathing (peaks
      up to 15% of hens) with no differences among litter substrates or ages (P >=
      0.18). On average, less than 2% of hens were observed foraging (peaks up to 4% of
      hens) with fewer hens foraging on AstroTurf(r) (P < 0.0001). Feather lipid
      differences among litter substrates (P < 0.0001) were inconsistent across
      sampling periods, possibly due to different birds sampled across time. At all
      ages, lipid levels were higher on the back over breast feathers (P < 0.0001) for
      hens housed with AstroTurf(r). AstroTurf(r) may be suitable for nest boxes, but
      straw and shavings are more ideal litter substrates. Further study should
      investigate alternative substrates or regular substrate addition to encourage
      more foraging and dust bathing.

PMID- 29050414
TI  - Serological survey of Reticuloendotheliosis virus infection in chickens in China
      in 2005 to 2015.
AB  - Reticuloendotheliosis virus (REV) causes an immunosuppressive, oncogenic, and
      runting syndrome in many avian hosts worldwide. The immunosuppression caused by
      REV can decrease the antibody levels of vaccines and subsequent increase
      susceptibility to secondary infections. There are no commercial vaccines or
      effective drugs to control REV infections at present. To investigate the REV
      infection status in chickens in China, 25,224 sera from 573 chicken flocks,
      collected between 2005 and 2015, were measured for REV antibodies using an enzyme
      linked immunosorbent assay. The seroprevalence of REV antibodies in the flocks
      was 56.20% (322/573) and the overall seroprevalence in individual chickens was
      13.91% (3,509/25,224). Of the 23 regions sampled, all provinces, except
      Heilongjiang, produced positive samples. Guangxi had the highest rate, of 57.84%.
      The virus-positive rate also tended to increase as the chickens aged. Our study
      indicates that REV infection has been common in China over the past decade.

PMID- 29050415
TI  - Influence of the incorporation mode of sugar beet pulp in the finishing diet on
      the digestive tract and performances of geese reared for foie gras production.
AB  - The aim of this work was to study the effects of incorporating sugar beet pulp
      (SBP) into the diet of geese in two feeding systems (complete pelleted feed or
      loose-mix feeding system) on crop development and performance. A total of 480 1-d
      old male geese were divided into three groups whose diet differed from d 56 to
      90: a complete pelleted diet containing 50% corn (control diet: AMEn 11.5 MJ/kg;
      CP 161 g/kg), and no SBP; a complete pelleted diet containing 50% corn and 10%
      SBP (SBPcp diet: AMEn: 11.5 MJ/kg; CP: 161 g/kg); and a mix in the same feeder
      (SBPlm diet) of 500 g/kg of protein-rich pellets containing 20% SBP (SBPprp:
      AMEn: 9.0 MJ/kg; CP: 250 g/kg) and 500 g/kg of whole corn (WC: AMEn: 14.0 MJ/kg;
      CP: 72 g/kg). Body traits, including crop volume, were measured at d 91. From d
      91 to 106, 88 birds/group were overfed with a mixture containing mainly corn and
      water before slaughter to measure fatty liver performance. Feed intake from d 56
      to 90 was higher (+10%; P = 0.004) in the SBPcp group than the other two, but at
      d 90, the body weight (BW) of the birds was higher (+7%; P = 0.002) in the SBPlm
      group than the other two. At d 91, the volume of the crop was greater in the
      SBPcp group (80.4 mL/kg of BW, P < 0.001) than in the control group (60.3 mL/kg
      of BW), the SBPlm group being intermediate (64.1 mL/kg of BW). Feed intake
      (13,321 g), weight gain (2,733 g), and feed-to-gain ratio (4.9) during the
      overfeeding period, as well as fatty liver weight (963 g) and commercial grading,
      were similar (P > 0.05) between the three groups. In conclusion, the use of sugar
      beet pulp in the diet of finishing geese helps the adaptation of the digestive
      tract to the overfeeding period, even in a loose-mix feeding system based on
      whole corn.

PMID- 29050416
TI  - Feeding broiler breeders a reduced balanced protein diet during the rearing and
      laying period impairs reproductive performance but enhances broiler offspring
      performance.
AB  - Mammalian studies have shown that nutritional constraints during the perinatal
      period are able to program the progeny (metabolism, performance). The presented
      research aimed to investigate if broiler breeders and their offspring performance
      could be influenced by reducing the dietary crude protein (CP) level with 25%. A
      total of 160 day-old pure line A breeder females were randomly divided over 2
      dietary treatments. The control group was fed commercial diets, whereas the
      reduced balanced protein (RP) breeders received an isoenergetic diet that was
      decreased with 25% in dietary CP and amino acid during their entire lifespan. The
      RP birds required an increased feed allowance, varying between 3 and 15%, to meet
      the same BW goals as their control fed counterparts. The difference in feed
      allocations and reduction of the dietary CP level resulted in a net protein
      reduction varying between 14 and 23%. At wk 27 and 40, the body composition of
      the breeders was changed as a result of the dietary treatment. At both ages, the
      proportional abdominal fat pad weight of the RP breeders was increased (P <
      0.001), whereas the proportional breast muscle weight was only higher at wk 27 in
      the control group compared to the RP group (P < 0.001). Egg weight (P < 0.001)
      and egg production (P < 0.001) was decreased for the RP fed birds. The lower
      dietary CP level reduced the proportional albumen weight of the RP eggs (P =
      0.006). Male offspring from RP breeders were characterized by an increase in BW
      from 28 d until 35 d of age (P = 0.015). Moreover, female progeny of RP breeders
      showed a reduced FCR (P = 0.025), whereas male progeny showed a tendency (P =
      0.052) towards a lower FCR at 5 wk of age. In conclusion, lowering dietary CP
      levels in rearing and laying phase of breeders had a negative effect on breeder
      performance but enhanced live performance of the offspring.

PMID- 29050417
TI  - Influence of swimming time in alleviating the deleterious effects of hot summer
      on growing Muscovy duck performance.
AB  - This experiment was conducted to observe the effects of varying swimming times
      (ST) of Muscovy ducks, raised in an open-sided house, in alleviating the
      deleterious effects of high temperature in hotter times of the day in the summer
      season on growth performance (body weight, average daily gain, feed consumption,
      and feed conversion ratio), carcass characteristics, body temperature, and some
      health aspects. We hypothesized that swimming times during the hottest periods of
      the day would show different performances. To test this hypothesis a total of 180
      Muscovy ducklings were randomly distributed into 4 equal groups in a completely
      randomized design experiment. All groups were raised under similar housing
      conditions. Birds of the first group (C) were raised in the indoor system and had
      no access to a swimming pond. While all birds of the second, third, and fourth
      groups (T1, T2, and T3) had access to a swimming pond during 10:00 to 12:00 h,
      12:00 to 14:00 h, and 14:00 to 16:00 h, respectively. The swimming pond
      (dimensions of 30 m length * 10 m width * 3 m depth with cement floor) was
      located in the front of the house. Vaccination and medical programs were
      undertaken according to the different ages under supervision of a licensed
      veterinarian. The obtained results indicated that swimming during 12:00 to 14:00
      h improved (P < 0.05) growth performance, dressed carcass, meat tenderness,
      lymphocyte, heterophils/lymphocytes ratio, body temperature, and mortality rate
      of Muscovy ducks. However, bone measurement, plumage conditions, foot pad
      dermatitis, hock discoloration, breast blisters score, and blood hematocrit
      values were insignificantly better in the group with access to the swimming pond
      during 12:00 to 14:00 h. In conclusion, raising ducks during hot conditions in an
      open-sided house with access to a swimming pond at 12:00 to 14:00 h is highly
      recommended due to the high BW, better immunity, decreased mortality rate, and
      low body temperature of ducks which was positively reflected in the health
      condition.

PMID- 29050418
TI  - Impact of egg disinfection of hatching eggs on the eggshell microbiome and
      bacterial load.
AB  - Disinfection of hatching eggs is essential to ensure high quality production of
      broilers. Different protocols are followed in different hatcheries; however, only
      limited scientific evidence on how the disinfection procedures impact the
      microbiome is available. The aim of the present study was to characterize the
      microbiome and aerobic bacterial load of hatching eggs before disinfection and
      during the subsequent disinfection steps. The study included a group of visibly
      clean and a group of visibly dirty eggs. For dirty eggs, an initial wash in
      chlorine was performed, hereafter all eggs were submitted to two times fumigation
      and finally spray disinfection. The eggshell microbiome was characterized by
      sequencing of the total amount of 16S rRNA extracted from each sample, consisting
      of shell surface swabs of five eggs from the same group. In addition, the number
      of colony forming units (cfu) under aerobic conditions was established for each
      disinfection step. The disinfection procedure reduced the bacterial load from
      more than 104 cfu (initially visibly clean eggs) and 105 cfu (initially visibly
      dirty eggs) to less than 10 cfu per sample after disinfection for both groups of
      eggs. The microbiome of both initially visibly clean and initially visibly dirty
      eggs had the highest abundances of the phyla Firmicutes, Proteobacteria and
      Bacteroidetes. Within the phyla Firmicutes the relative abundances of
      Clostridiales decreased while Lactobacillus increased from before to after final
      disinfection. In conclusion, the investigated disinfection procedure is effective
      in reducing the bacterial load, and by adding a chlorine wash for initially
      visibly dirty eggs, the microbiome of initially visibly clean and initially
      visibly dirty eggs had a highly similar microflora after the final disinfection
      step.

PMID- 29050419
TI  - Successful chilling of red-legged partridge (Alectoris rufa) sperm for use in
      artificial insemination.
AB  - The fertilizing capacity of pure, fresh avian semen may disappear in just half an
      hour, hindering its successful use in artificial insemination (AI) projects.
      Longer storage requires the use of infra-physiological temperatures and of semen
      diluents that help preserve the spermatozoa but that do not interfere with their
      fertilizing capacity. This study examines the effect on sperm quality of storing
      red-legged partridge sperm for 3 h at 5 degrees C with 2 different semen
      extenders: 1) a medium referred to as L&R-84, composed of sodium glutamate,
      glucose, magnesium acetate, potassium acetate, and polyvinylpyrrolidone, and 2)
      Lake 7.1 medium, composed of sodium glutamate, glucose, magnesium acetate,
      potassium citrate, and N,N-Bis(2-hydroxyethyl)taurine (BES). Extending with L&R
      84 returned better curvilinear velocity (P < 0.01), straight-line velocity (P <
      0.01), average path velocity (P < 0.01), linearity (P < 0.05), straightness (P <
      0.05), and wobble (P < 0.05) values, while extending with the Lake 7.1 medium was
      associated with higher percentages (P < 0.001) of motile sperm. The fertility
      rate was higher (P < 0.05) when birds were inseminated with L&R-84-extended sperm
      than with Lake 7.1-extended sperm. The mean number of penetrations of
      perivitelline layer samples (taken from above the germinal disc) was also higher
      for the L&R-84-extended sperm (P < 0.05). These results show L&R-84 can be
      recommended as an extender for red-legged partridge semen to be stored for at
      least 3 h at 5 degrees C.

PMID- 29050420
TI  - Iron requirements of broiler breeder hens.
AB  - A study was conducted to investigate Fe requirements of broiler breeders. One
      hundred-fifty-six Cobb 500 broiler breeder hens were individually placed in
      electrostatically painted cages at 22 weeks. The study was composed of an
      adaptation phase, in which hens were fed corn-soy-wheat bran diets until 35 wks.
      An Fe deficient mash diet (24.6 ppm Fe) was provided from 35 to 46 wk in order to
      induce a partial body Fe depletion. A production phase followed from 47 to 70 wk
      when hens were fed 6 diets with increasing Fe sulfate supplementation, which,
      upon analyses had 24.6, 48.6, 74.3, 99.6, 125.6, and 148.2 ppm Fe. Thirty
      hatching eggs from each treatment were randomly collected in the last wk of each
      production period and incubated. Hemoglobin and hematocrit were analyzed from 6
      hens as well as all hatched chicks per treatment. Analyses of production and
      hatching data were conducted using quadratic polynomial (QP), broken-line (BL),
      and exponential asymptotic (EA) models. Effects of dietary Fe were observed for
      total eggs and total hatching eggs, egg yolk Fe content, and hen and chick
      hematocrit and hemoglobin (P < 0.05). These responses to added Fe were optimized
      when dietary Fe were 96.8, 97.1, 130.6, 122.6, 120.0, and 125.0 ppm (QP) and
      76.4, 89.3, 135.0, 128.4, 133.8, and 95.0 ppm (BL) for total hatching eggs, egg
      yolk Fe content, and hen and chick hematocrit and hemoglobin, respectively.
      Optimization with the EA model was obtained for total hatching eggs, egg yolk Fe,
      and hen and chick hemoglobin at 97.9, 111.0, 77.9, and 96.3 ppm Fe for total
      hatching eggs, egg yolk Fe, and hen and chick hemoglobin, respectively. Adequate
      Fe levels are needed to maintain egg production as well as hatching chicks'
      indexes. Fe concentration in the yolk and diet are positively influenced. The
      average of all Fe requirement estimates obtained in the present study was 106 ppm
      total Fe, whereas averaged values for BL, QP, and EA models were 107, 113, and 97
      ppm Fe, respectively.

PMID- 29050421
TI  - Performance, nutrient utilization, and energy partitioning in broiler chickens
      offered high canola meal diets supplemented with multicomponent carbohydrase and
      mono-component protease.
AB  - Two broiler chicken experiments were conducted to investigate the effects of
      canola meal (CM) replacing soybean meal (SBM) in diets supplemented with
      carbohydrase and protease on performance and partitioning of energy. First, a 2 *
      2 * 2 factorial arrangement of treatments was employed to evaluate: protein meals
      (CM vs. SBM), carbohydrase (none or 300 mg/kg), protease (none or 200 mg/kg), and
      their interactions. Each treatment was fed to 6 replicated pens of 16 male
      broilers (Ross 308) from d 10 to 35. In the second experiment, 32 broiler chicks
      were used in a 2 * 2 factorial arrangement to investigate CM and carbohydrase
      effects on energy partitioning. Birds were transferred into 16 closed-circuit
      calorimeter chambers (4 chambers/diet; 2 birds/chamber) to measure heat
      production (HP), metabolizable and net energy (NE) by gaseous exchange, and total
      excreta collection from d 25 to 28. There were no 3-way interactions among
      experimental factors for any of the performance parameters measured. Birds given
      CM diets consumed less feed, had lower BW, and exhibited higher FCR compared to
      the control birds (P < 0.01). Both enzymes, alone or in combination, improved
      final BW and FCR (P < 0.05). There was an interaction between carbohydrase and
      protease for FCR over the grower period (P < 0.01), in which the combination of
      the enzymes resulted in further improvement of FCR. Energy, DM, and crude protein
      digestibility values were higher in control birds (P < 0.05). There was an
      interaction of protein meal and carbohydrase for HP, respiratory quotient (P <
      0.05), and NE:ME ratio of the diets (P = 0.06). Inclusion of CM without
      carbohydrase increased HP and decreased NE and NE:ME ratio of the diets (P <
      0.05). Carbohydrase decreased HP and increased retained energy (P = 0.06) and NE
      and NE:ME ratio (P < 0.05). In conclusion, high CM in the diet negatively affects
      growth performance through reduction in feed consumption, nutrient digestibility,
      and NE of the diet, which could partly be restored by enzyme supplementation.

PMID- 29050422
TI  - Effects of copper ions on the characteristics of egg white gel induced by strong
      alkali.
AB  - This study investigated the effects of copper ions on egg white (EW) gel induced
      by strong alkali. Changes in gel characteristics were examined through texture
      profile analysis, scanning electron microscopy (SEM), and chemical methods. The
      value of gel strength reached its maximum when 0.1% copper ions was added.
      However, the lowest cohesiveness values were observed at 0.1%. The springiness of
      gel without copper ions was significantly greater than the gel with copper ions
      added. SEM results illustrated that the low concentration of copper ions
      contributes to a dense and uniform gel network, and an open matrix was formed at
      0.4%. The free and total sulphhydryl group content in the egg white protein gel
      significantly decreased with the increased copper. The increase of copper ions
      left the contents of ionic and hydrogen bonds basically unchanged, hydrophobic
      interaction presented an increasing trend, and the disulfide bond exhibited a
      completely opposite change. The change of surface hydrophobicity proved that the
      main binding force of copper induced gel was hydrophobic interaction. However,
      copper ions had no effect on the protein component of the gels. Generally, a low
      level of copper ions facilitates protein-protein association, which is involved
      in the characteristics of gels. Instead, high ionic strength had a negative
      effect on gels induced by strong alkali.

PMID- 29050423
TI  - Effect of sodium selenite and selenium yeast on performance, egg quality,
      antioxidant capacity, and selenium deposition of laying hens.
AB  - This study compared the effects of sodium selenite and selenium yeast and their
      combination on laying performance, egg quality, antioxidant capacity, and
      selenium (Se) contents in tissues and eggs. Two-hundred-eighty-eight Jing Hong
      layers that were similar in laying rate (87.5 +/- 0.38%) and body weight (1.70 +/
      0.02 kg) were randomly distributed into 4 treatments for 11 wk (from 203 d old
      to 279 d old) with 9 replicates of 8 hens per replicate. The diets (corn-soybean
      meal diet) were supplemented with 0 [blank control (BC)], 0.3 mg/kg Se from
      sodium selenite (SS), 0.15 mg/kg Se from sodium selenite and 0.15 mg/kg Se from
      Se yeast (SS+SY), or 0.3 mg/kg Se from Se yeast (SY). Results showed that the
      laying rate of the SS+SY group increased significantly (P < 0.05) compared to the
      BC and SY groups. There were no differences (P > 0.05) in egg quality between the
      Se-supplemented diets and the BC diet. The serum glutathione peroxidase (GSH-Px)
      activity was increased (P < 0.01) in hens fed Se-supplemented diets compared to
      the BC diet. The liver superoxide dismutase (SOD) activity of the SY group was
      increased significantly (P < 0.05) compared to the BC group. Significant increase
      (P < 0.01) due to SY supplementation was noted in the serum vitamin E content
      compared to BC and SS. Layers fed Se-supplemented diets had higher (P < 0.01)
      contents of Se in the serum, liver, and kidney compared to the BC diet. Compared
      to BC, Se content in eggs was significantly increased (P < 0.05) by feeding
      supplementary Se. In conclusion, the effects of SS and Se yeast were
      approximately equal in promoting antioxidant capacity of laying hens, while Se
      yeast is easier to deposit into eggs and tissues. The diet with added equal
      amounts of the 2 sources of Se was more cost effective and affordable than a
      comparable amount of Se yeast to obtain the promising production performance and
      nearly similar Se deposition.

PMID- 29050424
TI  - A functional single nucleotide polymorphism in the tyrosinase gene promoter
      affects skin color and transcription activity in the black-boned chicken.
AB  - The tyrosinase (TYR) gene is the major melanogenesis-related gene for skin (fur)
      or plumage color in mammals and birds. Genetic variation in the promoter region
      of a gene may affect gene expression and phenotypes. This study compared the TYR
      promoter region between pooled DNA (n = 8) of chickens (Gallus gallus) with black
      and white skin using direct sequencing. The single nucleotide polymorphism (SNP)
      c.-2228A>T was found to have the opposite allele distribution in the two groups.
      The results of genotyping in a larger population (n = 188) revealed that SNP c.
      2228A>T was associated with the skin color of the black-boned chicken.
      Individuals with genotypes AA and AT had greater TYR expression than those with
      genotype TT. A luciferase assay of the promoter activity revealed that genotype
      AA had greater activity than genotype TT. Transcription factor binding site
      analyses showed that the c.-2228A allele has a putative binding site for
      transcription factor AT-rich interaction domain 3a (Arid3a), while the c.-2228T
      allele has sites for GS homeobox 2 (GSX2), homeobox D9 (Hoxd9), and mix paired
      like homeobox (MIXL1). We concluded that the TYR promoter polymorphism affects
      skin color. SNP c.-2228A>T could be used as a genetic marker for marker-assisted
      selection of skin color in the black-boned chicken.

PMID- 29050425
TI  - Sodium butyrate improved performance while modulating the cecal microbiota and
      regulating the expression of intestinal immune-related genes of broiler chickens.
AB  - This study evaluated the effect of sodium butyrate (SB) on performance,
      expression of immune-related genes in the cecal tonsils, and cecal microbiota of
      broiler chickens when dietary energy and amino acids concentrations were reduced.
      Day-old male Ross 708 broiler chicks were fed dietary treatments in a 3 * 2
      factorial design (8 pens per treatment) with 3 dietary formulations (control
      diet; reduction of 2.3% of amino acids and 60 kcal/kg; and reduction of 4.6% of
      amino acids and 120 kcal/kg) with or without the inclusion of 0.1% of SB. Feed
      intake (FI), body weight gain (BW gain), and feed conversion ratio (FCR) were
      recorded until 28 d of age. From 14 to 28 d, there was an interaction of nutrient
      density by SB (P = 0.003) wherein BW gain of birds fed SB was impaired less by
      the energy/amino acids reduction than unsupplemented birds. A similar result was
      obtained from 1 to 28 d (P = 0.004). No interaction (P < 0.05) between nutrient
      density by SB was observed for FCR. Nutritional density of the diets and SB
      modified the structure, composition, and predicted function of the cecal
      microbiota. The nutritionally reduced diet altered the imputed function performed
      by the microbiota and the SB supplementation reduced these variations, keeping
      the microbial function similar to that observed in chickens fed a control diet.
      The frequency of bacterial species presenting the butyryl-CoA: acetate CoA
      transferase gene increased in the microbiota of chickens fed a nutritionally
      reduced diet without SB supplementation, and was not changed by nutrient density
      of the diet when supplemented with SB (interaction; P = 0.01). SB modulated the
      expression of immune related genes in the cecal tonsils; wherein SB upregulated
      the expression of A20 in broilers fed control diets (P < 0.05) and increased IL-6
      expression (P < 0.05). These results show that SB had positive effects on the
      productive performance of broilers fed nutritionally reduced diets, partially by
      modulating the cecal microbiota and exerting immune-modulatory effects.

PMID- 29050426
TI  - Influence of hot exposure on 12-week-old turkey hen physiology, welfare, and meat
      quality and 16-week-old turkey tom core body temperature when crated at transport
      density.
AB  - The influence of hot conditions on 12-week-old turkey hens and 16-week-old toms
      while crated at transport density was evaluated. Forty-eight hens and 48 toms (8
      birds per flock * 3 flocks * 2 humidity levels) were used in neutral treatments
      (trt; 20 degrees C), and 16 hens and 16 toms (8 birds per flock * 1 flock * 2
      humidity levels) were used in the hot trt (35 degrees C). Birds were placed in
      crates at a transport stocking density of approximately 83 kg/m2, then inside a
      pre-conditioned chamber for 8 hours. Live shrink, core body temperature (CBT),
      heterophil/lymphocyte (H/L) ratio, and breast and thigh pH and color were
      recorded. Differences were declared significant at P <= 0.05. Live shrink after
      exposure to the 35 degrees C trt (4.92%) was greater (P < 0.0001) than when birds
      were exposed to 20 degrees C (1.48%). The 35 degrees C trt (P < 0.0001) had
      higher Delta CBT (final minus initial) compared to the 20 degrees C trt. The 35
      degrees C trt also caused higher (P < 0.0001) H/L ratio, 4.07 vs. 1.57 for the 20
      degrees C trt. Breast (P = 0.0110) and thigh pH levels (P < 0.0001) measured 27 h
      postmortem were lower for the 35 degrees C trt at 5.64 and 5.73 compared to the
      20 degrees C trt at 5.70 and 5.92, respectively. Breast meat from birds exposed
      to 35 degrees C was darker (P < 0.0001), while the color of thigh meat was
      unaffected. Toms quickly became distressed in the hot conditions, forcing those
      tests to be aborted. Only CBT data were analyzed. The CBT increased at a mean
      rate of 0.09 degrees C/min for hens at both RH levels, while the CBT of toms
      increased at 0.12 and 0.18 degrees C/min when exposed to 35 degrees C, 30%; and
      35 degrees C, 80%, respectively. Exposure to hot temperatures caused higher CBT,
      greater live shrink, and greater H/L ratio. Toms were more greatly affected than
      hens to the hot trt, with CBT increasing at a greater rate.

PMID- 29050427
TI  - Brazil nut meal and spray-dried egg powders as alternatives to synthetic
      methionine in organic laying hen diets.
AB  - The United States organic poultry industry is currently facing a limitation on
      dietary inclusion of synthetic methionine (Met). This study investigated Brazil
      nut protein powder (BNPP), spray-dried egg white (SDEW), and spray-dried egg
      blend (70:30 albumen: yolk) (SDEB) as alternatives to synthetic Met in organic
      laying hen diets. A total of 270 Hy-Line Brown laying hens was fed 5 diets from
      22 to 38 wk of age, with 6 replicates of 3 adjacent cages per diet and 3 hens per
      cage. Diets included a commercial control (COM) (non-organic with standard CP and
      synthetic Met), an organic control (ORG) (with no synthetic Met, but higher CP to
      meet Met requirements), and 3 organic treatment diets with no synthetic Met, but
      including BNPP, SDEW, or SDEB at levels to meet Met requirements. Egg production
      and quality, body weight (BW), feed intake, and manure nutrients and ammonia were
      assessed. Data were analyzed using the PROC MIXED procedure of SAS, with Tukey's
      test used for multiple mean comparisons, and P <= 0.05 was deemed statistically
      significant. Body weight was greatest for the COM diet, and feed conversion
      improved for hens fed egg-based diets compared to controls. Egg weight and
      production did not differ between COM and treatment diets. The SDEW diet had
      greater albumen height and Haugh units compared to ORG and BNPP diets and greater
      percent albumen compared to COM and BNPP diets. Specific gravity was greatest for
      BNPP fed hens. Manure DM and potash were highest from COM and BNPP diets,
      respectively. Both egg-based diets increased ammonia flux relative to the COM
      diet. The BNPP and egg-based diets were lower in cost for $/metric tonne, $/dozen
      eggs, and $/kg of eggs compared to the ORG diet. The ingredients assessed herein
      could, therefore, cost-effectively replace synthetic Met in organic hen diets
      without negatively impacting egg production.

PMID- 29050428
TI  - Effect of an organic acids based feed additive and enrofloxacin on the prevalence
      of antibiotic-resistant E. coli in cecum of broilers.
AB  - Increasing antibiotic resistance is a major public health concern.
      Fluoroquinolones are used to treat and prevent poultry diseases worldwide.
      Fluoroquinolone resistance rates are high in their countries of use. The aim of
      this study was to evaluate the effect of an acids-based feed additive, as well as
      fluoroquinolone antibiotics, on the prevalence of antibiotic-resistant E. coli. A
      total of 480 broiler chickens (Ross 308) were randomly assigned to 3 treatments:
      a control group receiving a basal diet; a group receiving a feed additive (FA)
      based on formic acid, acetic acid and propionic acid; and an antibiotic
      enrofloxacin (AB) group given the same diet, but supplemented with enrofloxacin
      in water. A pooled fecal sample of one-day-old chicks was collected upon arrival
      at the experimental farm. On d 17 and d 38 of the trial, cecal samples from each
      of the 8 pens were taken, and the count of E. coli and antibiotic-resistant E.
      coli was determined.The results of the present study show a high prevalence of
      antibiotic-resistant E. coli in one-day-old chicks. Supplementation of the diet
      with FA and treatment of broilers with AB did not have a significant influence on
      the total number of E. coli in the cecal content on d 17 and d 38 of the trial.
      Supplementation with FA contributed to better growth performance and to a
      significant decrease (P <= 0.05) in E. coli resistant to ampicillin and
      tetracycline compared to the control and AB groups, as well as to a decrease (P
      <= 0.05) in sulfamethoxazole and ciprofloxacin-resistant E. coli compared to the
      AB group. Treatment with AB increased (P <= 0.05) the average daily weight
      compared to the control group and increased (P <= 0.05) the number of E. coli
      resistant to ciprofloxacin, streptomycin, sulfamethoxazole and tetracycline; it
      also decreased (P <= 0.05) the number of E. coli resistant to cefotaxime and
      extended spectrum beta-lactamase- (ESBL-) producing E. coli in the ceca of
      broilers.

PMID- 29050429
TI  - Isolation and genetic characterization of a novel adeno-associated virus from
      Muscovy ducks in China.
AB  - Adeno-associated virus (AAV; genus Dependoparvovirus, family Parvoviridae) was
      first discovered in 1965 as a contaminant in adenovirus preparations. The AAVs
      are generally considered non-pathogenic, and they have the ability to attenuate
      the replication of other more pathogenic viruses, which makes them attractive as
      potential therapeutics or preventative measures. This study characterized a novel
      AAV isolated from Muscovy ducks in China. The novel virus (MHH-05-2015) was
      isolated after propagating a field isolate of the DAdV-3 virus (a type 3 duck
      adenovirus) in duck embryo fibroblasts. The full genome sequence of MHH-05-2015
      was determined, and the nucleotide and amino acid sequences were compared to
      other avian AAVs. The genomic distribution of the structural and non-structural
      protein-coding genes in MHH-05-2015 was conserved and consistent with the other
      AAVs. Compared to previously isolated avian AAVs, MHH-05-2015 had approximately
      63 to 64% sequence identity. Phylogenetic analysis indicated that MHH-05-2015
      clustered separately from other avian AAVs, suggesting that MHH-05-2015 was not
      directly descended from other Dependoparvovirus family members. These results
      suggest that MHH-05-2015 is a new subtype of AAV that is distinct from other
      avian AAVs.

PMID- 29050430
TI  - Extraction and physicochemical characterization of broiler (Gallus gallus
      domesticus) skin gelatin compared to commercial bovine gelatin.
AB  - Gelatin was extracted from broiler (Gallus gallus domesticus) skins and analyzed
      to compare its physicochemical properties with those of commercial bovine
      gelatin. The average yield of broiler skin gelatin was 6.5% on a wet weight
      basis. Broiler skin gelatin had more alpha1-and alpha2-chains than beta-chain and
      contained high molecular weight (gamma-chain) polymers. Glycine was the dominant
      amino acid in broiler skin gelatin (20.26%), followed by proline (Pro) (15.12%)
      then hydroxyproline (Hyp) (11.36%). Compared to commercial bovine gelatin,
      broiler skin gelatin had less total imino acids (Pro and Hyp) but a higher (33.65
      vs. 31.38 degrees C) melting temperature (P < 0.01). The differences in physical
      properties between the broiler and commercial bovine gelatins appeared to be
      associated with differences in their amino acid composition and molecular weight
      distribution. The sensory evaluation results revealed that broiler skin gelatin
      could be a potential alternative to commercial bovine gelatin, useful in various
      food products.

PMID- 29050431
TI  - A study on the sternum growth and mineralization kinetic of meat duck from 35 to
      63 days of age.
AB  - The sternum as an important part of the skeleton and not only provides a crucial
      attachment site for the pectoral muscles and protects internal organs such as the
      heart and lungs for meat duck, but may also be considered as the primary
      ventilator in the avian respiratory system. Therefore, this study focuses on the
      sternum growth and mineralization kinetics of ducks from 35 d to 63 d of age. A
      total of 72 one-d-old males and 72 females were chosen and fed with the same diet
      until the age of 9 weeks. The sternum and serum were harvested at 35 d, 42 d, 49
      d, 56d, and 63 d of feeding. Results showed that the sternum width rapidly grew
      from 35 d to 42 d and the value changed little after 42 d, while the keel length
      and the sternum depth did not significantly change until 49 d age. The sternum
      defatted weight and density increased assumed to "S" with ducks' age and their
      plateau in the 56 d. The sternum ash content, calcium (Ca), and phosphate (P)
      levels increased with duck age, then all three reached a plateau in 49 days.
      Similarly, serum alkaline phosphatase (ALP) activity was higher in the ducks at
      both 35 and 42 days, followed by 49 days, and the value was lowered to a minimum
      on both days 56 and 63. Conversely, serum tartrate resistant acid phosphatase
      (TRAP) activity substantially increased until 49 days irrespective of duck
      gender. Results indicate that the dimensions of the sternum were already at the
      maximum in 49-day-old ducks and the sternum of the ducks rapidly mineralized from
      42 d to 49 d of age and achieved a plateau phase after 49-days resulting from the
      high activity of ALP at the sternum early mineralization.

PMID- 29050432
TI  - Dietary sugarcane bagasse and coarse particle size of corn are beneficial to
      performance and gizzard development in broilers fed normal and high sodium diets.
AB  - An experiment was conducted to evaluate the effects of sugarcane bagasse (SB) and
      particle size on broiler performance, gizzard development, ileal microflora,
      litter quality, and bird welfare under a wet litter challenge model. A total of
      672 one-day-old Ross 308 male broilers was allocated to 48 pens using a 2 * 2 * 2
      factorial arrangement of treatments with corn particle size-coarse 3,576 MUm (CC)
      or fine 1,113 MUm (FC) geometric mean diameter, SB - 0 or 2% and sodium (Na) -
      0.16 or 0.40% with increased Na level to induce wet litter. A 3-way particle size
      * Na * SB interaction (P < 0.05) was observed for weight gain at d 10. Birds fed
      FC showed a higher weight gain compared to birds fed CC when 0.40% Na without SB
      diet or 0.16% Na with 2% SB diet was offered. A significant particle size * SB
      interaction was observed at d 24 on feed conversion ratio (FCR; P < 0.001) and
      weight gain (P < 0.05). FCR was reduced by 2% SB supplementation in birds fed CC
      but increased in birds fed FC. Further, weight gain of birds fed 2% SB was higher
      in birds fed CC but not in those fed FC. On d 35, birds fed 2% SB had a higher
      weight gain (P < 0.001) compared to those without SB, and a SB * particle size
      interaction on relative gizzard weight (P < 0.05) and pH (P < 0.05) was present.
      SB reduced gizzard pH and increased the relative gizzard weight in birds fed the
      FC diet but not the CC diet (P < 0.05). Counts of ileal Bacillus spp. were
      increased in birds fed SB (P < 0.05) on d 24. No effects of SB and particle size
      on litter quality and bird welfare were observed, but higher Na increased litter
      moisture and footpad dermatitis (FPD) scores (P < 0.001). These findings suggest
      that SB independently or in combination with CC improves performance in older
      birds regardless of Na level in diets, possibly through improved gizzard
      development and gut microflora of birds.

PMID- 29050433
TI  - Effect of the addition of glycosaminoglycans on bone and cartilaginous
      development of broiler chickens.
AB  - Locomotion issues in broiler production may decrease performance (carcass yield
      and traits) and lead to high financial losses. This study evaluates the addition
      of glucosaminoglycans in broiler diets to minimize the lack of proper bone
      development and joint weakening. The experiment was conducted using 2,160
      broilers randomly distributed in a factorial pattern (3 * 3) using 3 levels of
      glucosamine sulfate (0, 0.12, and 0.24%) and 3 levels of chondroitin sulfate
      addition (0, 0.08, and 0.16%). Eight repetitions were used for each treatment,
      distributed in 72 pens with 30 broilers each. There was a quadratic effect on
      feed conversion for broilers from 1 to 42 d old (P = 0.0123) for the addition of
      chondroitin, and better feed conversion was obtained by adding 0.08% of
      chondroitin. The relative tibia weight, the width of the proximal epiphysis and
      diaphysis presented a linear increased effect in broilers at 42 d old. An
      interaction was found between the amount of chondroitin * glucosamine and the
      number of chondrocytes in the proximal cartilage of the tibia (P = 0.0072). There
      was a quadratic effect of glucosamine levels (P = 0.0107) in the birds that had
      received the 0.16% addition of chondroitin, and the presence of 0.18% glucosamine
      increased the number chondrocytes in the cartilage of broilers. These results
      provide the first evidence that broilers may benefit from increased dietary
      chondroitin sulfate. These results indicate that the addition of glucosamine and
      chondroitin sulfates in broiler feed rations might alleviate leg conditions and
      decrease financial losses in the broiler industry.

PMID- 29050434
TI  - Microbial loads and antibiotic resistance patterns of Staphylococcus aureus in
      different types of raw poultry-based meat preparations.
AB  - The hygiene status of raw chicken-meat preparations from retail outlets in North
      Western Spain was investigated. Microbial counts (aerobic plate counts (APCs),
      psychrotrophs, Enterobacteriaceae, fecal coliforms, enterococci, pseudomonads,
      fluorescent pseudomonads, yeasts and molds, and Staphylococcus aureus) were
      determined for minced meat, hamburgers, nuggets, white sausages, red sausages,
      escalope, and roll-ups. S. aureus isolates were tested for susceptibility to
      twenty antimicrobials of veterinary and human clinical significance (disc
      diffusion method, CLSI). Average microbial loads (log10 cfu/g) ranged from 2.63
      +/- 0.80 (enterococci) to 6.66 +/- 1.09 (psychrotrophs). Average APCs (6.44 +/-
      1.16 log10 cfu/g) were regarded as acceptable according to EU microbiological
      criteria. The type of product had an influence (P < 0.05) on microbial loads,
      samples of escalope showing the highest counts for most microbial groups. Two
      thirds (66.7%) of the samples tested harbored S. aureus. All the S. aureus
      isolates were multi-resistant (to between three and fifteen antibiotics). The
      greatest prevalence of resistance was shown for ampicillin, oxacillin, penicillin
      G, ceftazidime, and nalidixic acid. The results of this study show that poultry
      based meat preparations present high microbial loads and are a major reservoir of
      antibiotic-resistant S. aureus strains. This highlights the need for correct
      handling of such foodstuffs with a view to reducing risks to consumers.

PMID- 29050435
TI  - Immune-enhancing activity of phosvitin by stimulating the production of pro
      inflammatory mediator.
AB  - Egg yolk phosvitin is one of the most phosphorylated proteins in nature, and the
      extraordinarily high concentration of phosphate groups in its structure provides
      a strong metal-binding ability. Phosvitin is known to possess various functional
      activities, including metal-chelating, antioxidant, emulsifying, antimicrobial,
      and cytotoxic activities. However, little is known about the immune-enhancing
      activity of phosvitin. The objective of this study was to evaluate the immune
      enhancing activity of phosvitin in murine RAW 264.7 macrophages. Griess reagents
      and quantitative real-time PCR were used to determine the effect of phosvitin (at
      12.5, 25, 50, and 100 MUg/mL) on the levels of pro-inflammatory mediators NO and
      inducible nitric oxide synthase (iNOS), cytokines TNF-alpha and IL-1beta in RAW
      264.7 macrophages. The effect of phosvitin on the phagocytic activity of RAW
      264.7 macrophages was also measured using the Neutral-Red Uptake method.
      Lipopolysaccharides was used as a positive control. Phosvitin significantly (P <
      0.05) increased the production of NO in RAW 264.7 macrophages in a dose-dependent
      manner, but did not show any cytotoxicity. The amounts of NO produced were 3.47,
      7.12, 10.23, and 14.57 MUM in 12.5 to 100 MUg/mL range of phosvitin (control:
      0.46 MUM). Compared with the untreated group, phosvitin treatment at a 100 MUg/mL
      level increased the production of NO by 31.67 times. Phosvitin also significantly
      increased the mRNA expression of the RAW 264.7 macrophages: 100 MUg/mL of
      phosvitin treatment increased the expression of mRNA for iNOS, TNF-alpha, and IL
      1beta by 46.25, 9.09, and 85.18 times of the control, respectively. The
      phagocytic activity of RAW 264.7 macrophages was also increased significantly by
      phosvitin treatment. These results demonstrated that phosvitin dramatically
      improved the immune functions RAW 264.7 macrophages by enhancing the production
      of immune mediators and increasing phagocytic activity. Therefore, phosvitin has
      a potential to be used as an immune-enhancing agent by food or nutraceutical
      industries.

PMID- 29050436
TI  - Sound analysis to model weight of broiler chickens.
AB  - The pattern of body weight gain during the commercial growing of broiler chickens
      is important to understand growth and feed conversion ratio of each flock.The
      application of sound analysis techniques has been widely studied to measure and
      analyze the amplitude and frequency of animal sounds. Previous studies have shown
      a significant correlation (P <= 0.001) between the frequency of vocalization and
      the age and weight of broilers. Therefore, the aim of this study was to identify
      and validate a model that describes the growth rate of broiler chickens based on
      the peak frequency of their vocalizations and to explore the possibility to
      develop a tool capable of automatically detecting the growth of the chickens
      based on the frequency of their vocalizations during the production cycle. It is
      part of an overall goal to develop a Precision Livestock Farming tool that
      assists farmers in monitoring the growth of broiler chickens during the
      production cycle. In the present study, sounds and body weight were continuously
      recorded in an intensive broiler farm during 5 production cycles. For each cycle
      the peak frequencies of the chicken vocalizations were used to estimate the
      weight and then they were compared with the observed weight of the birds
      automatically measured using on farm automated weighing devices. No significant
      difference is shown between expected and observed weights along the entire
      production cycles; this trend was confirmed by the correlation coefficient
      between expected and observed weights (r = 96%, P value <= 0.001).The identified
      model used to predict the weight as a function of the peak frequency confirmed
      that bird weight might be predicted by the frequency analysis of the sounds
      emitted at farm level. Even if the precision of the weighing method based on
      sounds investigated in this study has to be improved, it gives a reasonable
      indication regarding the growth of broilers opening a new scenario in monitoring
      systems in broiler houses.

PMID- 29050437
TI  - Development and validation of a novel SNP panel for the genetic characterization
      of Italian chicken breeds by next-generation sequencing discovery and array
      genotyping.
AB  - The aim of this study was to compare the intra and inter genetic variability and
      population structure of 7 indigenous chicken breeds of the Veneto region, through
      a novel panel of 64 SNP, each located in an exonic region and mostly on different
      chromosomes. A total of 753 blood samples from 7 local chicken breeds
      (Ermellinata di Rovigo, Millefiori di Lonigo, Polverara, Pepoi, Robusta Lionata,
      Robusta Maculata, and Padovana) was collected and analyzed. Two strains of
      Polverara (Nera and Bianca) and Padovana (Dorata and Camosciata) were included in
      the study. The observed heterozygosity ranged from 0.124 (Pepoi) to 0.244
      (Ermellinata di Rovigo), and the expected heterozygosity varied from 0.132
      (Millefiori di Lonigo) to 0.300 (Ermellinata di Rovigo). Global FIS results
      (0.114) indicated a low-medium inbreeding effect, with values ranging from 0.008
      (Millefiori di Lonigo) to 0.223 (Ermellinata di Rovigo). Pairwise FST values
      (0.167) for all populations ranged from 0.020 (Polverara Nera and Polverara
      Bianca) to 0.193 (Robusta Lionata and Polverara Nera), indicating that the
      studied breeds were genetically highly differentiated. The software STRUCTURE was
      used to detect the presence of population substructures, and the most probable
      number of clusters (K) of the 10 chicken populations was at K = 8. The
      affiliation was successful in all Veneto chicken breeds. The present SNP marker
      results, compared with previous data obtained using microsatellites, provided a
      reliable estimate of genetic diversity within and between the studied breeds, and
      demonstrated the utility of the proposed panel as a rapid, efficient, and cost
      effective tool for periodical monitoring of the genetic variability among poultry
      populations. In addition, the present SNP panel could represent a resource for a
      systematic approach with relevant impact on breeding program decisions and could
      turn out to be a reliable tool for genetic traceability of indigenous chicken
      meat. Adoption of a periodical monitoring system of genetic diversity is a
      fundamental tool in conservation actions and should increase the value of typical
      and niche products.

PMID- 29050438
TI  - Effects of rearing systems on laying performance, egg quality, and serum
      biochemistry of Xianju chickens in summer.
AB  - The objective of this study was to compare the laying performance, egg quality,
      and serum biochemistry of hens maintained in conventional cage rearing system
      (CRS), flat net-rearing system (NRS), and free range system (FRS) under summer
      conditions. Indigenous Xianju chickens (n = 540) were randomly allocated into
      cages or pens of rearing system groups, within each system there were 5
      replicates with 36 hens in each replicate. The experiment lasted between 21 and
      29 wk of age. Hen-day egg production (P = 0.00) and egg mass (P = 0.00) were
      higher in the CRS but were similar in the NRS and FRS. Lowest egg weight (P =
      0.02), yolk weight (P = 0.00) and yolk ratio (P = 0.01), and feed intake (P =
      0.01) were observed from the FRS, whereas lowest feed conversion ratio (FCR) was
      recorded from the CRS (P = 0.01). Rearing systems had negligible effect on egg
      quality. Serum Ca (P = 0.04) and total protein (P = 0.03) levels were found to be
      higher in the CRS but were lower in the FRS. Serum levels of glucose (P = 0.01),
      cholesterol (P = 0.00), and triglyceride (P = 0.00) in the CRS increased compared
      with the NRS and FRS groups, whereas serum levels of high density lipoprotein
      cholesterol (HDL-C; P = 0.01) in the CRS decreased. It can be concluded that
      under summer conditions, Xianju chickens from CRS had an advantage in terms of
      productivity parameters, but exhibited higher levels of serum lipids and glucose.

PMID- 29050439
TI  - Pathogenicity and immunosuppressive potential of fowl adenovirus in specific
      pathogen free chickens.
AB  - To elucidate the effect of fowl adenovirus (FAdV)-C in specific-pathogen-free
      (SPF) chickens, we investigated the pathogenicity, body weights, enzymatic
      systems, and immune organs of chickens in response to Newcastle disease virus
      (NDV) and avian influenza virus subtype H9 (AIV-H9) vaccination. Chickens were
      divided randomly into four groups, which included injection groups (FAdV-C,
      vaccination, and FAdV-C plus vaccination) and a negative control group. The
      results indicated that FAdV-C was highly pathogenic in SPF chickens and led to a
      40% mortality rate and growth retardation, compared with the control birds.
      Significant changes in clinical chemical markers of all infected birds, together
      with histopathological lesions, indicated impairment of the liver and heart
      integrity and function. Furthermore, chickens in the FAdV-C plus vaccination
      group had significantly lower titers of antibodies against NDV and AIV-H9 than
      the uninfected and vaccinated chickens. The results of this study provide new
      insights into the pathogenesis of hydropericardium syndrome, a disease that
      progresses to a metabolic disorder and causes serious growth retardation and
      immunosuppression.

PMID- 29050440
TI  - Random regression analyses to model the longitudinal measurements of yolk
      proportions in the laying chicken.
AB  - Cubic spline function was used in a genetic evaluation to model the change of
      yolk proportion over the lay life. A total of 19,862 yolk proportion records of
      2,324 hens was used. The evaluated submodels consisted of 3 to 6 knot models. The
      same knots were fitted for genetic and permanent environmental splines. The
      residual effects were specified to be independently and normally distributed, but
      with heterogeneous variance for each test week. (Co)variance components were
      estimated by the average information restricted maximum likelihood (AIREML)
      method. The best fitting random regression model (RRM) was a submodel with 4
      knots at 32, 36, 52, and 72 wk of age for genetic and permanent environmental
      effects. The estimate of genetic variance was larger than that of permanent
      environmental variance at the same time point. The heritability of yolk
      proportion ranged from 0.32 to 0.55, and the repeatability ranged between 0.45
      and 0.73. The genetic correlations between test wk were from moderate to unity.
      To the best of our knowledge, this was the first report on the use of a RRM to
      evaluate yolk proportion. The results of this study showed that random regression
      models with the spline function could be used for improvement of yolk proportion.

PMID- 29050442
TI  - Correlated responses to long-term divergent selection for 8-week body weight in
      female White Plymouth Rock chickens: Sexual maturity.
AB  - Reported here are correlated responses for reproductive traits to long-term
      divergent selection (54 generations) for 8-week body weight (BW8). Comparisons
      involved both selected and relaxed lines. Traits measured were age at first egg
      (AFE), body weight at first egg (WFE), and ratio of body weight and age at first
      egg (WAFE). Although sexual maturity was delayed in the selected lines, the
      effect was more pronounced in the low than high selected and relaxed lines.
      Selection for low BW resulted in decreases in WFE and WAFE. Correlated responses
      to selection for high BW were increased WFE and WAFE. Minimum AFE, WFE, and WAFE
      in relation to sexual maturity were line specific and influenced by selection for
      BW8. WAFE provided a "yardstick" for target body weights that were optimum for
      successful attainment of sexual maturity and higher reproductive rates. Such may
      be line specific. There was opposition between relaxed and artificial selection,
      resulting in a higher reproductive performance and fitness for the former.

PMID- 29050441
TI  - The physiological response of broiler chickens to the dietary supplementation of
      the bacteriocin nisin and ionophore coccidiostats.
AB  - The aim of this study was to investigate the effect of dietary supplementation
      with nisin alone or in combination with salinomycin or monensin on broiler
      chickens in terms of growth performance, selected blood parameters, digestive
      enzyme activity, apparent nutrient digestibility, and tibiotarsus mineralization,
      as well as selected gastrointestinal tract (GIT) organ weights, intestinal
      length, and central immune organ weights. Two independent experiments, each
      including 400 one-day-old female Ross 308 chicks differing in ionophore
      coccidiostats, i.e., salinomycin and monensin supplementation, were conducted.
      The following treatments were applied: experiment 1: NA-no additives, SAL
      salinomycin (60 mg/kg diet), NIS-nisin (2,700 IU/kg diet), SAL+NIS-salinomycin
      (60 mg/kg diet) and nisin (2,700 IU/kg diet); experiment 2: NA-no additives, MON
      monensin (100 mg/kg diet), NIS-nisin (2,700 IU/kg diet) and MON+NIS-monensin (100
      mg/kg diet) and nisin (2,700 IU/kg diet). The addition of nisin with or without
      ionophores to the birds' diet improved broiler growth performance in terms of BWG
      and FCR (days 1 to 14) and BWG and FI (15 to 35 d; 1 to 35 d). Salinomycin showed
      effects similar to those of nisin influence on growth performance (1 to 35 d),
      while monensin supplementation resulted in lower BWG. Moreover, no additive
      effect between nisin and ionophores was observed. Nisin and salinomycin had no
      influence on the serum concentration of selected hormones and other blood
      biochemical parameters except glucose, which was reduced by nisin. A decrease in
      lipase activity was observed during nisin and salinomycin supplementation, while
      the apparent ileal digestibility of fat was not affected. However, the
      digestibility of crude protein increased with nisin administration. Additionally,
      the effects of nisin on decreasing the weight and length of GIT segments were
      observed. Supplementation with nisin and monensin was not associated with a
      negative impact on tibiotarsus mineralization and the immune organ index. This
      study suggests that nisin may be used in broiler nutrition as a growth promotor,
      with no negative influence on the bird's metabolism or immune status.

PMID- 29050443
TI  - Microbial endocrinology: Why the intersection of microbiology and neurobiology
      matters to poultry health.
AB  - The union of microbiology and neurobiology has led to a revolution in the way we
      view the microbiome. Now recognized as important symbionts, the microorganisms
      which inhabit multiple niches in mammalian and avian (chicken) hosts, such as the
      intestinal tract and skin, serve and influence many important physiological
      functions. The realization that the gut microbiome serves as a kind of "microbial
      organ" has important implications for many areas of biology. In this paper
      advances in the field of microbial endocrinology which may hold relevance for the
      poultry industry are examined.

PMID- 29050444
TI  - Treatment of ichthyosis vulgaris with a urea-based emulsion: videodermatoscopy
      and confocal microscopy evaluation.
AB  - BACKGROUND: Ichthyosis vulgaris is a common disorder of keratinization caused by
      mutations in the filaggrin gene and clinically characterized by variable degree
      of xerosis. METHODS: Five patients affected by ichthyosis vulgaris and moderate
      to severe xerosis of the lower limbs, were treated twice daily for 30 days with
      an emulsion containing 10% urea, ceramides, and natural moisturizing factors
      (NMF). Evaluation was performed at baseline and at the end of treatment by
      clinical examination, Visual Analogue Scale to quantify itch, videodermatoscopy
      (VD), and reflectance confocal microscopy (RCM). Patients were also asked to
      provide an acceptability rating of the product based on spreadability,
      absorbency, odor, pleasantness and ease of application. RESULTS: At the end of
      treatment the tested urea-based emulsion resulted in a significant clinical
      improvement of xerosis in all patients. The product determined a remarkable
      reduction of itch, it was well tolerated and it had a good cosmetic
      acceptability. VD and RCM objectively confirmed the reduction/disappearance of
      scales and the improvement/normalization of furrow's size and morphology.
      CONCLUSIONS: The tested urea-based emulsion represents a valid option for the
      treatment of xerosis in patients affected by ichthyosis vulgaris. VD and RCM
      confirmed to be useful non-invasive techniques for the therapeutic monitoring of
      this condition.

PMID- 29050445
TI  - What's new in the treatment of eczemas.
AB  - BACKGROUND: We have conducted an open label, non-comparative study in order to
      assess the efficacy and tolerability of Dexyane Med in combination with
      corticosteroids in patients with chronic hand eczema (CHE) and contact eczema
      (CE) in a real-life setting. METHODS: Twenty patients, 10 with CHE and 10 with
      CE, have been enrolled in the study. After the enrollment and the baseline
      evaluation, patients were treated with topical mometasone once daily and Dexyane
      Med once daily for one week, followed by Dexyane Med twice daily for three weeks.
      After the enrollment visit, patients were seen at the end of treatment, after
      four weeks. A telephone contact was foreseen at the second week. During the
      visits, mTLSS Score (CHE patients only), IGA Score and VAS for pruritus and pain
      were calculated. Patients' satisfaction was recorded during the phone contact
      after two weeks of treatment and at the final visit. Tolerability was evaluated
      at the end of the study. RESULTS: All patients experienced a remarkable
      improvement in mTLSS Score, IGA Score (from a mean of 2.8 to 0.5) and VAS (from
      4.5 to 0.6 for pruritus and from 2.9 to 0.3 for pain). The treatment was well
      tolerated and all patients were satisfied or very satisfied either at the second
      week or at the end of the study. CONCLUSIONS: Our study has shown that the
      treatment of chronic hand eczema and contact eczema with a medical device
      administered twice a day for three weeks, following a one week treatment in
      combination with a topical corticosteroid, is effective in decreasing the burden
      of symptoms and well tolerated. To confirm our data, further controlled trials
      are warranted in order to explore the efficacy and tolerability of Dexyane Med in
      different types of eczema.

PMID- 29050446
TI  - Management of mycoses in daily practice.
AB  - The guideline recommendations, albeit founded on thorough reviews of clinically
      relevant literature data, are often not immediately adaptable to everyday life.
      Considering the marked heterogeneity of superficial mycoses, each of them
      requires specific management in a real life context; in all cases diagnostic
      confirmation is required with microscopic and culture examination. In tinea
      capitis oral therapy is necessary (minimum six weeks) and should be continued
      until clinical and, above all, mycological healing. In cases of tinea corporis,
      cruris or pedis, it may be necessary to associate oral therapy to topical
      treatment. The main oral antifungals are fluconazole, itraconazole and
      terbinafine. Fluconazole has favorable pharmacokinetic and pharmacodynamic
      characteristics, and is effective in most superficial mycoses, for example in
      cases of diffuse or recurrent pityriasis versicolor in which oral therapy with an
      azole derivative is useful. Topical treatment, lasting 6-12 months, is indicated
      in onychomycosis that is confined to one nail. In frequent cases of onychomycosis
      involving multiple nails or recurrence, oral therapy is necessary.
      Pharmacological history is important, given the possible interactions of some
      systemic drugs. In chronic or recurrent relapsing vulvovaginitis, first-choice
      therapy is oral fluconazole with a therapeutic regimen that respects the mycotic
      biorhythm (200 mg on days 1, 4, 11, 26, and subsequently 200 mg/week for 3
      months).

PMID- 29050447
TI  - Uncaria tomentosa.
AB  - Uncaria tomentosa (U. tomentosa) or una de gato, a species of vine of Rubiaceae
      family, was used from centuries in various medical conditions. Although there are
      no randomized controlled trials or published human outcome studies, some
      conditions reportedly improved by U. tomentosa include osteoarthritis, rheumatoid
      arthritis, prostatitis, viral illnesses and cancer (acting as a non-specific
      immunomodulantign agent) and it may also have potential as an immunomodulating
      adaptogen in cellular aging. The understanding of some specific mechanisms of
      molecular action leads to the demonstration of various anti-inflammatory,
      immunostimulating and protective effects. These results bring the strong
      hypothesis that U. tomentosa could be effective in the topical treatment of
      dermatological manifestation, namely rosacea.

PMID- 29050448
TI  - Bullous impetigo during interstitial pneumonitis.

PMID- 29050449
TI  - Doubling golimumab doses did not improve skin disease in two obese patients with
      psoriatic arthritis.

PMID- 29050450
TI  - Combined carbon dioxide laser with photodynamic therapy for the treatment of
      nodular and infiltrative basal cell carcinoma.

PMID- 29050451
TI  - A case of an inverse Klippel-Trenaunay Syndrome.

PMID- 29050452
TI  - Erosive pustular dermatosis of the leg: an uncommon entity?

PMID- 29050453
TI  - Cutaneous lipomatosis: diagnosing a rare condition.

PMID- 29050454
TI  - Amelanotic desmoplastic melanoma arising on an occipito-parietal burn scar.

PMID- 29050455
TI  - Apocrine papillary cystadenoma and basal cell carcinoma: an unusual collision
      tumor.

PMID- 29050456
TI  - Perforating granuloma annulare within the red dye of a tattoo.

PMID- 29050457
TI  - Skin nodules in onset of acute myeloid leukemia, a myelomonocytic variant case.

PMID- 29050458
TI  - Endoscopic Treatment of Jejunal Heterotopic Gastric Mucosa that Caused Recurrent
      Intussusception.
AB  - Heterotopic gastric mucosa (HGM) is a rare anomaly in the small bowel and may be
      the cause of intussusception when it gets a lead point in the jejunum. All cases
      of intussusception due to intestinal HGM have been treated with surgical
      resection. A 5-year-old girl presented with chief complaints of vomiting and
      abdominal pain for 2 weeks. A computed tomography scan of the abdomen showed
      intussusception at the proximal jejunal loops. Three air reductions and one
      saline reduction were attempted without success. She continued to be symptomatic,
      and endoscopic evaluation was performed. Enteroscopy revealed some variable-sized
      polypoid mucosal lesions with erosions on the proximal jejunum. Endoscopic
      mucosal resection was performed using a snare. The resected tissues
      histologically showed a hyperplastic polyp arising from the HGM. Her symptoms did
      not recur within 1 year after the treatment. Our case showed that enteroscopy
      could be useful for the diagnosis and management of jejunal intussusception
      caused by HGM.

PMID- 29050459
TI  - Third-party regulatory T cells prevent murine acute graft-versus-host disease.
AB  - BACKGROUND/AIMS: Adoptive therapy with regulatory T (Treg) cells to prevent graft
      versus-host disease (GVHD) would benefit from a strategy to improve homing to the
      sites of inflammation following hematopoietic stem cell transplantation (HSCT).
      Although donor-derived Treg cells have mainly been used in these models, third
      party-derived Treg cells are a promising alternative for cell-based
      immunotherapy, as they can be screened for pathogens and cell activity, and
      banked for GVHD prevention. In this study, we explored major histocompatibility
      complex (MHC) disparities between Treg cells and conventional T cells in HSCT to
      evaluate the impact of these different cell populations on the prevention of
      acute GVHD, as well as survival after allogeneic transplantation. METHODS: To
      induce acute GVHD, lethally irradiated BALB/c (H-2d) mice were transplanted with
      5 * 105 T cell-depleted bone marrow cells and 5 * 105 CD4+CD25- splenic T cells
      from C57BL/6 (H-2b) mice. Recipients were injected with 5 * 105 cultured donor-,
      host-, or third-party-derived CD4+CD25+CD62L+ Treg cells (bone marrow
      transplantation + day 1). RESULTS: Systemic infusion of three groups of Treg cell
      improved clinicopathological manifestations and survival in an acute GVHD model.
      Although donor-derived Treg cells were immunologically the most effective, the
      third-party-derived Treg cell therapy group displayed equal regulation of
      expansion of CD4+CD25+- Foxp3+ Treg cells and suppressive CD4+IL-17+ T-helper
      (Th17) cells in ex vivo assays compared with the donor- and host-derived groups.
      CONCLUSION: Our findings demonstrate that the use of third-party Treg cells is a
      viable alternative to donor-derived Treg cellular therapy in clinical settings,
      in which human leukocyte antigen-matched donors are not always readily available.

PMID- 29050460
TI  - Predialysis hyponatremia and mortality in elderly patients beginning to undergo
      hemodialysis.
AB  - BACKGROUND/AIMS: Predialysis hyponatremia has been recently reported to be
      associated with mortality in incident hemodialysis patients. However, whether
      hyponatremia is associated with unfavorable outcomes in elderly patients remains
      unknown. We hypothesized that nephrology referral inf luences hyponatremia, and
      aimed to define how nephrology referral affects the association between
      hyponatremia and mortality in the elderly. METHODS: We retrospectively assessed
      mortality in 599 incident hemodialysis patients aged >= 70 at a tertiary
      university hospital, between 2000 and 2010. We analyzed 90-day and 1-year all
      cause mortality (ACM) in relation to predialysis serum sodium (sNa). We divided
      the patients into two groups according to predialysis glucose-corrected sNa:
      hyponatremia (< 135 mmol/L) and normonatremia (135 to 145 mmol/L). RESULTS: Low
      estimated glomerular filtration rate, high phosphorus, low albumin,
      nonpreparation of arteriovenous fistula or graft, and late referral were
      associated with a low sNa in the elderly. Among 599 patients, 106 and 174
      patients died at the 90-day and 1-year follow-ups, respectively. Each 10-mmol/L
      increase in predialysis sNa tended to be associated with lower 90-day and 1-year
      ACM. When patients were stratified by nephrology referral, hyponatremia was
      associated with increased mortality in early referral group (90-day ACM: hazard
      ratio [HR] = 2.335, p = 0.041; 1-year ACM: HR = 1.790, p = 0.024). However,
      hyponatremia was not associated with mortality in late referral group.
      CONCLUSION: Predialysis hyponatremia at hemodialysis initiation is associated
      with late referra.

PMID- 29050462
TI  - A growing hepatic mass in a cryptogenic cirrhosis patient.

PMID- 29050461
TI  - Comparison of clinical utility between diaphragm excursion and thickening change
      using ultrasonography to predict extubation success.
AB  - BACKGROUND/AIMS: Both diaphragmatic excursion and change in muscle thickening are
      measured using ultrasonography (US) to assess diaphragm function and mechanical
      ventilation weaning outcomes. However, which parameter can better predict
      successful extubation remains to be determined. The aim of this study was to
      compare the clinical utility of these two diaphragmatic parameters to predict
      extubation success. METHODS: This study included patients subjected to extubation
      trial in the medical or surgical intensive care unit of a university-affiliated
      hospital from May 2015 through February 2016. Diaphragm excursion and percent of
      thickening change (Deltatdi%) were measured using US within 24 hours before
      extubation. RESULTS: Sixty patients were included, and 78.3% (47/60) of these
      patients were successfully extubated, whereas 21.7% (13/60) were not. The median
      degree of excursion was greater in patients with extubation success than in those
      with extubation failure (1.65 cm vs. 0.8 cm, p < 0.001). Patients with extubation
      success had a greater Deltatdi% than those with extubation failure (42.1% vs.
      22.5%, p = 0.03). The areas under the receiver operating curve for excursion and
      Deltatdi% were 0.836 (95% confidence interval [CI], 0.717 to 0.919) and 0.698
      (95% CI, 0.566 to 0.810), respectively (p = 0.017). CONCLUSIONS: Diaphragm
      excursion seems more accurate than a change in the diaphragm thickness to predict
      extubation success.

PMID- 29050463
TI  - Clinical outcomes and pathological characteristics of immunoglobulin G4-related
      ophthalmic disease versus orbital inflammatory pseudotumor.
AB  - Background/Aims: This study investigated the clinical and pathological features
      of immunoglobulin G4 (IgG4)-related ophthalmic disease. To clarify the features,
      we compared IgG4-related ophthalmic disease and orbital inflammatory pseudotumor.
      Methods: We retrospectively reviewed the medical records of 103 patients who were
      initially diagnosed with orbital inflammatory pseudotumor, and identified 16
      cases in which the diagnosis was based on surgical biopsy and for which data in
      medical records were sufficient for analysis. Immunohistochemical staining of
      pathological specimens for IgG and IgG4 was performed. Finally, six of IgG4
      related ophthalmic disease patient and 10 of orbital inf lammatory pseudotumor
      patient were analyzed. Results: The IgG4-related ophthalmic disease group had
      more IgG4-positive plasma cells and a higher IgG4/IgG plasma cell ratio than the
      orbital inflammatory pseudotumor group. Collagenous fibrosis and lacrimal gland
      involvement were significantly more frequent in the IgG4-related ophthalmic
      disease group. Dense lymphocyte infiltration, obliterative phlebitis, and
      bilateral lesions were more frequent in IgG4-related ophthalmic disease, but the
      differences were not significant. The recurrence-free period was shorter in the
      IgG4-related ophthalmic disease group (p = 0.035). Conclusions: The location of
      the lesion (lacrimal gland), count and ratio of IgG4-positive plasma cells, and
      collagenous fibrosis aid the diagnosis of IgG4-related ophthalmic disease in
      patients with idiopathic orbital mass-like lesions. In addition, maintenance
      therapy should be considered in patients with IgG4-related ophthalmic disease to
      prevent recurrence.

PMID- 29050465
TI  - Epidermoid splenic cyst with elevated serum level of CA19-9.

PMID- 29050466
TI  - Pectus excavatum: a rare cause of gastric subepithelial lesion.

PMID- 29050464
TI  - Anti-platelet effects of epigallocatechin-3-gallate in addition to the
      concomitant aspirin, clopidogrel or ticagrelor treatment.
AB  - BACKGROUND/AIMS: Although epigallocatechin-3-gallate (EGCG), which is found in
      high contents in the dried leaves of green tea, has been reported to have an anti
      platelet effect, synergistic effects of EGCG in addition to current anti-platelet
      medications remains to be elucidated. METHODS: Blood samples were obtained from
      40 participants who took aspirin (ASA, n = 10), clopidogrel (CPD, n = 10),
      ticagrelor (TCG, n = 10) and no anti-platelet medication (Control, n = 10). Ex
      vivo platelet aggregation and adhesion under various stimulators were analyzed by
      multiple electrode aggregometry (MEA) and Impact-R systems. PAC-1 and P-selectin
      expressions in human platelets were analyzed by flow cytometry. RESULTS: In MEA
      analysis, adenosine diphosphate (ADP) and thrombin receptor activating peptide
      (TRAP)-induced platelet aggregations were lower in the CPD and the TCG groups;
      arachidonic acid (AA)-induced platelet aggregation was lower in the ASA group,
      whereas collagen (COL)-induced platelet aggregations were comparable among four
      groups. EGCG significantly reduced ADP- and COL-induced platelet aggregation in
      dose-dependent manner (ADP, p = 0.04; COL, p < 0.01). There were no additional
      suppressions of platelet aggregation stimulated by AA in the ASA group, and by
      ADP in the CPD and TCG groups. Moreover, EGCG suppressed shear stress-induced
      platelet adhesion on Impact-R, and had no effect on P-selectin and PAC-1
      expressions. CONCLUSIONS: Ex vivo treatment of EGCG inhibited platelet adhesion
      and aggregation without changes in P-selectin and PAC-1 expression. There was no
      additional suppressions in platelet aggregation stimulated by AA in the ASA group
      and ADP in the CPD and TCG groups.

PMID- 29050467
TI  - Sequence Effect on the Formation of DNA Minidumbbells.
AB  - The DNA minidumbbell (MDB) is a recently identified non-B structure. The reported
      MDBs contain two TTTA, CCTG, or CTTG type II loops. At present, the knowledge and
      understanding of the sequence criteria for MDB formation are still limited. In
      this study, we performed a systematic high-resolution nuclear magnetic resonance
      (NMR) and native gel study to investigate the effect of sequence variations in
      tandem repeats on the formation of MDBs. Our NMR results reveal the importance of
      hydrogen bonds, base-base stacking, and hydrophobic interactions from each of the
      participating residues. We conclude that in the MDBs formed by tandem repeats, C
      G loop-closing base pairs are more stabilizing than T-A loop-closing base pairs,
      and thymine residues in both the second and third loop positions are more
      stabilizing than cytosine residues. The results from this study enrich our
      knowledge on the sequence criteria for the formation of MDBs, paving a path for
      better exploring their potential roles in biological systems and DNA
      nanotechnology.

PMID- 29050468
TI  - Impact of Polymer Type and Relative Humidity on the Long-Term Physical Stability
      of Amorphous Solid Dispersions.
AB  - The purpose of this work is to compare the long-term physical stability of
      amorphous solid dispersion (ASD) formulations based on three different
      commercially used excipients, namely, poly(vinylpyrrolidone) K25 (PVP),
      poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64), and hydroxypropyl
      methylcellulose acetate succinate 126G (HPMCAS), at standardized ICH storage
      conditions, 25  degrees C/0% relative humidity (RH), 25  degrees C/60% RH, and 40
      degrees C/75% RH. Acetaminophen (APAP) and naproxen (NAP) were used as active
      pharmaceutical ingredients (APIs). 18 month long stability studies of these
      formulations were analyzed and compared with the API/polymer phase diagrams,
      which were modeled and predicted by applying the Perturbed-Chain Statistical
      Associating Fluid Theory (PC-SAFT) and the Gordon-Taylor or Kwei equation. The
      study showed that, at dry storage, the solubility of the APIs in the polymers and
      the kinetic stabilizing ability of the polymers increase in the following order:
      HPMCAS < PVPVA64 < PVP. RH significantly reduces the kinetic stabilization as
      well as NAP solubility in the polymers, while the impact on APAP solubility is
      small. The impact of RH on the stability increases with increasing hydrophilicity
      of the pure polymers (HPMCAS < PVPVA64 < PVP). The experimental stability results
      were in very good agreement with predictions confirming that PC-SAFT and the Kwei
      equation are suitable predictive tools for determining appropriate ASD
      compositions and storage conditions to ensure long-term physical stability.

PMID- 29050470
TI  - Development of a Novel Leak-Free Constant-Pressure Cylinder for Certified
      Reference Materials of Liquid Hydrocarbon Mixtures.
AB  - Liquid hydrocarbon mixtures such as liquefied petroleum gas and liquefied natural
      gas are becoming integral parts of the world's energy system. Certified reference
      materials (CRMs) of liquid hydrocarbon mixtures are necessary to allow assessment
      of the accuracy and traceability of the compositions of such materials. A piston
      type constant-pressure cylinder (PCPC) comprising chambers for a pressurizing gas
      (helium) and liquid (hydrocarbons) separated by a piston can be used to develop
      accurate and traceable liquid hydrocarbon mixture CRMs. The development of
      accurate CRMs relies on the maintenance of their composition. However, a PCPC
      might allow hydrocarbons to leak owing to the imperfect seal of the piston. In
      this study, a novel leak-free bellows-type constant-pressure cylinder (BCPC) is
      designed and evaluated by comparison with PCPCs. Liquid hydrocarbon mixtures
      consisting of ethane, propane, propene, isobutane, n-butane, 1-butene, and
      isopentane were prepared in both types of constant pressure cylinders and then
      monitored to check leakages between the gas and liquid chambers. Overall, notable
      leakage occurred from and into both chambers in the PCPCs, whereas no leakage
      occurred in the BCPCs in the three months after their gravimetric preparation.
      The BCPCs maintained no leakage even 10 months after their preparation, whereas
      the PCPCs showed significantly increasing leakage during the same period.

PMID- 29050471
TI  - Understanding the Selective Detection of Fe3+ Based on Graphene Quantum Dots as
      Fluorescent Probes: The Ksp of a Metal Hydroxide-Assisted Mechanism.
AB  - Graphene quantum dots (GQDs) have been widely used as fluorescence probes to
      detect metal ions with satisfactory selectivity. However, the diverse chemical
      structures of GQDs lead to selectivity for multiple metal ions, and this can lead
      to trouble in the interpretation of selectivity due to the lack of an in depth
      and systematic analysis. Herein, bare GQDs were synthesized by oxidizing carbon
      black with nitric acid and used as fluorescent probes to detect metal ions. We
      found that the specific ability of GQDs to recognize ferric ions relates to the
      acidity of the medium. Specifically, we demonstrated that the coordination
      between GQDs and Fe3+ is regulated by the pH of the aqueous GQDs solution.
      Dissociative Fe3+ can coordinate with the hydroxyl groups on the surface of the
      GQDs to form aggregates (such as iron hydroxide), which induces fluorescence
      quenching. A satisfactory selectivity for Fe3+ ions was achieved under relatively
      acidic conditions; this is because of the extremely small Ksp of ferric hydroxide
      compared to those of other common metal hydroxides. To directly survey the key
      parameter for Fe3+ ion specificity, we performed the detection experiment in an
      environment free of interference from the buffer solution, noninherent groups,
      and other complex factors. This study will help researchers understand the
      selectivity mechanisms of GQDs as fluorescence probes for metal ions, which could
      guide the design of other GQD-based sensor platforms.

PMID- 29050469
TI  - In Vivo [18F]GE-179 Brain Signal Does Not Show NMDA-Specific Modulation with Drug
      Challenges in Rodents and Nonhuman Primates.
AB  - As one of the major excitatory ion channels in the brain, NMDA receptors have
      been a leading research target for neuroscientists, physicians, medicinal
      chemists, and pharmaceutical companies for decades. Molecular imaging of NMDA
      receptors by means of positron emission tomography (PET) with [18F]GE-179 quickly
      progressed to clinical PET studies, but a thorough understanding of its binding
      specificity has been missing and has thus limited signal interpretation. Here a
      preclinical study with [18F]GE-179 in rodents and nonhuman primates (NHPs) is
      presented in an attempt to characterize [18F]GE-179 signal specificity. Rodent
      PET/CT was used to study drug occupancy and functional manipulation in rats by
      pretreating animals with NMDA targeted blocking/modulating drug doses followed by
      a single bolus of [18F]GE-179. Binding competition with GE-179, MK801, PCP, and
      ketamine, allosteric inhibition by ifenprodil, and brain activation with
      methamphetamine did not alter the [18F]GE-179 brain signal in rats. In addition,
      multimodal imaging with PET/MRI in NHPs was used to evaluate changes in
      radiotracer binding as a function of pharmacological challenges. Drug-induced
      hemodynamic changes were monitored simultaneously using functional MRI (fMRI).
      Comparisons of baseline and signal after drug challenge in NHPs demonstrated that
      the [18F]GE-179 signal cannot be manipulated in a predictable fashion in vivo.
      fMRI data acquired simultaneously with PET data supported this finding and
      provided evidence that radiotracer delivery is not altered by blood flow changes.
      In conclusion, the [18F]GE-179 brain signal is not readily interpretable in the
      context of NMDA receptor binding on the basis of the results shown in this study.

PMID- 29050472
TI  - Peptide-Mediated Membrane Transport of Macromolecular Cargo Driven by Membrane
      Asymmetry.
AB  - Pep-1 is a cell-penetrating peptide that represents a powerful strategy for
      delivering large, hydrophilic therapeutic molecules into cells. Model membranes,
      such as lipid vesicles and planar bilayers, have been useful for investigating
      the direct translocation of cell-penetrating peptides. Here, we present a droplet
      interface bilayer-based approach to quantify pep-1-mediated beta-galactosidase
      translocation. We found that beta-galactosidase translocation is driven only by
      the negative transmembrane potential resulting from the asymmetric bilayers. The
      asymmetric droplet interface bilayer method may be generally applicable for high
      throughput screening of the efficacy of cell-penetrating peptides.

PMID- 29050473
TI  - Fluorescent Silicon Nanorods-Based Ratiometric Sensors for Long-Term and Real
      Time Measurements of Intracellular pH in Live Cells.
AB  - Long-term and real-time investigation of the dynamic process of pHi changes is
      critically significant for understanding the related pathogenesis of diseases and
      the design of intracellular drug delivery systems. Herein, we present a one-step
      synthetic strategy to construct ratiometric pH sensors, which are made of
      europium (Eu)-doped one-dimensional silicon nanorods (Eu@SiNRs). The as-prepared
      Eu@SiNRs have distinct emission maxima peaks at 470 and 620 nm under 405 nm
      excitation. Of particular note, the fluorescence emission intensity at 470 nm
      decreases along with the increase of pH, while the one at 620 nm is nearly
      unaffected by pH changes, making Eu@SiNRs a feasible probe for pH sensing
      ratiometrically. Moreover, Eu@SiNRs are found to be responsive to a broad pH
      range (ca. 3-9), biocompatible (e.g., ~100% of cell viability during 24 h
      treatment) and photostable (e.g., ~10% loss of intensity after 40 min continuous
      UV irradiation). Taking advantages of these merits, we employ Eu@SiNRs for the
      visualization of the cytoplasmic alkalization process mediated by nigericin in
      living cells, for around 30 min without interruption, revealing important
      information for understanding the dynamic process of pHi fluctuations.

PMID- 29050474
TI  - Release of Solubilizate from Micelle upon Core Freezing.
AB  - By combining NMR (yielding 1H chemical shift, spin relaxation, and self-diffusion
      data) and small-angle X-ray scattering experiments, we investigate the complex
      temperature dependence of the molecular and aggregate states in aqueous solutions
      of the surfactant [CH3(CH2)17(OCH2CH2)20OH], abbreviated as C18E20, and
      hexamethyldisiloxane, HMDSO. The latter molecule serves as a model for
      hydrophobic solubilizates. Previously, the pure micellar solution was
      demonstrated to exhibit core freezing at approximately 7-8  degrees C. At room
      temperature, we find that HMDSO solubilizes at a volume fraction of approximately
      10% in the core of the C18E20 micelles, which consists of molten and thereby
      highly mobile alkyl chains. Upon lowering the temperature, core freezing is
      found, just like in pure micelles, but at a temperature shifted significantly to
      3  degrees C. The frozen cores contain immobile alkyl chains and exhibit a higher
      density but are essentially devoid (volume fraction below 1%) of the
      solubilizate. The latter molecules are released, first gradually and then rather
      steeply, from the core in the temperature range that is roughly delimited by the
      two core freezing temperatures, one for pure micelles and one for micelles with
      solubilizates. The release behavior of systems with different initial HMDSO
      loading follows the same master curve. This feature is rationalized in terms of
      loading capacity being strongly temperature dependent: upon lowering the
      temperature, release commences once the loading capacity descends below the
      actual solubilizate content. The sharp release curves and the actual release
      mechanism with its molecular features shown in rich detail have some bearing on a
      diverse class of possible applications.

PMID- 29050479
TI  - Quantifying Young's moduli of protein fibrils and particles with bimodal force
      spectroscopy.
AB  - Force spectroscopy is a means of obtaining mechanical information of individual
      nanometer-scale structures in composite materials, such as protein assemblies for
      use in consumer films or gels. As a recently developed force spectroscopy
      technique, bimodal force spectroscopy relates frequency shifts in cantilevers
      simultaneously excited at multiple frequencies to the elastic properties of the
      contacted material, yet its utility for quantitative characterization of
      biopolymer assemblies has been limited. In this study, a linear correlation
      between experimental frequency shift and Young's modulus of polymer films was
      used to calibrate bimodal force spectroscopy and quantify Young's modulus of two
      protein nanostructures: beta-lactoglobulin fibrils and zein nanoparticles. Cross
      sectional Young's modulus of protein fibrils was determined to be 1.6 GPa while
      the modulus of zein nanoparticles was determined as 854 MPa. Parallel measurement
      of beta-lactoglobulin fibril by a competing pulsed-force technique found a higher
      cross-sectional Young's modulus, highlighting the importance of comparative
      calibration against known standards in both pulsed and bimodal force
      spectroscopies. These findings demonstrate a successful procedure for measuring
      mechanical properties of individual protein assemblies with potential use in
      biological or packaging applications using bimodal force spectroscopy.

PMID- 29050481
TI  - MicroRNA-497 suppress osteosarcoma by targeting MAPK/Erk pathway.
AB  - BACKGROUND: The aim of this study was to study the mechanism of miRNA-497 in the
      apoptosis of osteosarcoma cells. METHODS: MG-63 cells were divided into the three
      groups: NC, BL and miRNA groups, NC group were treated with nothing; BL group
      were transfected with blank vector; miRNA group were transfected with miRNA-497.
      Cell proliferation rate was detected by MTT method; Apoptosis rate was detected
      by flow cytometry and measuring the gene and protein expression of MAPK, Erk and
      P 21 by RT-PCR and Western blot. RESULTS: The cell proliferation rate of miRNA
      group was significantly lower compared to NC group and BL group (p < 0.05); while
      the apoptosis rate of miRNA group (32.17 +/- 3.23 %) was significantly higher
      than that of NC group  (8.40 +/- 1.78 %) and BL group (8.83 +/- 0.99 %) (p <
      0.05, respectively). Regarding the gene expression detection, we found that gene
      and protein expressions of MAPK, Erk and P21 of miRNA group were significantly
      different compared to NC and BL groups (p < 0.05, respectively). CONCLUSION: MiR
      497 can activate P21 expression by inhibiting the expression of MAPK/Erk
      signaling pathway, thus promoting the apoptosis of osteosarcoma cells (Fig. 5,
      Ref. 18).

PMID- 29050480
TI  - The effect of leptin and resveratrol on JAK/STAT pathways and Sirt-1 gene
      expression in the renal tissue of ischemia/reperfusion induced rats.
AB  - OBJECTIVE: Our study aimed to investigate the possible modifying effects of
      leptin and combined use of resveratrol on rat renal I/R injury and their
      relationship on signal pathways and apoptosis-related mechanisms. BACKGROUND:
      Renal ischemia-reperfusion (I/R) injury is an important cause of acute renal
      failure. METHODS: Male Sprague Dawley rats were divided into 5 groups: Control,
      I/R, I/R+leptin, I/R+resveratrol and I/R+leptin+resveratrol. Leptin (10 MUg/kg
      BW) was administered (i.p.) 30 min prior to I/R. Resveratrol was administered by
      gavage at 20 mg/kg BW per d for 12 d prior to I/R. The left renal artery was
      exposed to 1 h of ischemia and 1 h of reperfusion. RESULTS: Resveratrol treatment
      alone increased TNF-alpha, TNF-alpha R1, NF-kappaB, SIRT-1, STAT1 and STAT3 mRNA
      levels and decreased caspase 3 protein levels. Leptin treatment alone
      significantly decreased the caspase 3 protein levels. The combined use of
      resveratrol and leptin significantly increased STAT3, and caspase 3 mRNA levels,
      and decreased the caspase 3 protein levels. Apoptosis was significantly decreased
      especially in the leptin and leptin+resveratrol groups. CONCLUSION: The present
      study suggest that a combined use of resveratrol and leptin has preventive and
      regulatory effects on renal I/R injury; the mechanism involves decreasing
      apoptosis, likely by altering the JAK/STAT pathway and SIRT1 expression (Fig. 8,
      Ref. 24).

PMID- 29050482
TI  - The effect of sulforaphane on oxidative stress and inflammation in rats with
      toxic hepatitis induced by acetaminophene.
AB  - OBJECTIVE: The aim of the present study was to reveal the possible effect of
      sulforaphane on oxidative stress and inflammation in rats liver with toxic
      hepatitis induced by acetaminophene. BACKGROUND: Sulforaphane is a compound with
      high antioxidant properties. Acetaminophen, which is a para-aminophenol
      derivative, can lead to fatal hepatic necrosis with direct hepatotoxic effects at
      high doses. METHODS: Thirty six male Sprague-Dawley rats were randomly divided
      into four groups. Control group (n = 9) was fed with standard rat chow and water
      for 3 days. Group APAP (n = 9) received a single dose acetaminophen 1 g/kg by
      oral gavage in addition to standard chow and water. Group SFN (n = 9) received
      sulforaphane 500 MUg/kg by oral gavage in addition to standard chow and water for
      3 days. Group APAP+SFN (n = 9) received sulforaphane 500 MUg/kg and a single dose
      acetaminophen 1 g/kg by oral gavage in addition to standard chow and water.
      Acetaminophen was administered three hours after SFN administration. RESULTS:
      Neopterin, MDA, AST, ALT and CRP levels of group APAP were significantly
      increased compared to control group. GSH level of group APAP was significantly
      lower than in the control group. CONCLUSION: Sulforaphane is a protective agent
      against acetaminophen-induced liver damage and it can be added in the treatment
      protocol (Tab. 1, Fig. 5, Ref. 51).

PMID- 29050483
TI  - Phthalate induced toxicity in prostate cancer cell lines and effects of alpha
      lipoic acid.
AB  - OBJECTIVE: The effects of dimethyl phthalate, diethyl phthalate, diisobutyl
      phthalate, di-n-butyl phthalate, benzylbutyl phthalate, di-2-ethylhexyl phthalate
      were investigated on human prostate cancer cell lines DU145 and PC3 in vitro.
      MATERIALS AND METHODS: Standards of dimethyl phthalate, diethyl phthalate, di
      isobutyl phthalate, dibutyl phthalate, benzyl butyl phthalate, and di-ethyl hexyl
      phthalate were used. Alpha lipoic acid was used as antioxidant compound. DU145
      and PC3 human prostate carcinoma cells were used. MTT assay were used for
      cytotoxicity assay. RESULTS: A low dose proliferative effect of phthalates in
      vitro was observed. With the hypothesis of the inhibition of aerobic glycolysis
      activity in cancer treatment, alpha-lipoic acid was applied to cells; where as a
      contrary to previous studies, no change in the cell proliferation was observed.
      In combination with ALA, at IC50 and lower doses, an increase of the cytotoxic
      effect was found for DIBP, DBP and BBP; while for DMP, DEP and DEHP, a decrease
      was observed for DU145 cells. In PC3 cells, a decrease was observed for DMP, DEP
      and DBPs; while no significant difference were observed for DEHP, DIBP and BBP.
      CONCLUSSION: The present study demonstrates preliminary information regarding the
      low dose proliferative effects of phthalates in prostate cancer in vitro (Tab. 2,
      Fig. 2, Ref. 65).

PMID- 29050484
TI  - eNOS and XRCC4 VNTR variants contribute to formation of nicotine dependence
      and/or schizophrenia.
AB  - BACKGROUND: This study aimed to evaluate whether VNTR variants in the Endothelial
      Nitric Oxide Synthase (eNOS) and the XRCC4 gene play any role in nicotine
      dependence (ND) and/or Schizophrenia+ND (Sch+ND) ethiopathogenesis. METHODS:
      Present study included 100 individuals with ND, 60 patients with Sch+ND, and 70
      healthy controls. These variants were analyzed using PCR. RESULTS: The cases with
      ND had higher eNOS VNTR-BB genotype than the healthy control subjects (p =
      0.001). eNOS-AA genotype was lower in cases with Sch+ND and ND groups compared to
      the controls (p = 0.001, p = 0.001, respectively). eNOS-B allele was found
      significantly more frequently in Sch+ND group compared to the controls (p =
      0.001). eNOS-A allele was significantly lower in ND group than the controls (p =
      0.001). XRCC4-ID genotype was more common in the ND group than the control group
      (p = 0.001) as heterozygosity disadvantage. XRCC4-DD genotype was more common in
      the Sch+ND group compared to the controls (p = 0.035). The frequency of XRCC4-I
      allele was lower in the Sch+ND group compared to the controls (p = 0.012).
      CONCLUSIONS: Our results showed that eNOS and XRCC4 VNTR variants might play a
      potential role in Sch+ND and/or ND pathophysiology (Tab. 2, Ref. 48).

PMID- 29050485
TI  - Giant inguinoscrotal hernia repair.
AB  - Giant inguinoscrotal hernia is defined as an inguinal hernia extending below the
      midpoint of inner thigh in standing position. The authors describe giant
      inguinoscrotal hernia and small umbilical hernia with 12 years history of this
      uncommon disease. After preoperative evaluation, US and CT examination he was
      operated on. It was very difficult to return the hernia sac contents back to the
      abdomen and additional infraumbilical incision was needed. Hernioplasty suo modo
      without mesh was done. Patient recovered uneventfully. In the discussion the
      authors present the newer classification of giant inguinal hernia, the current
      treatment options and known serious complications of surgery. Finally, it
      indicates that good treatment results can only be achieved by close cooperation
      of concerned professionals in the treatment and intensive intraoperative and
      postoperative patient monitoring (Fig. 9, Ref. 31).

PMID- 29050486
TI  - Long-term outcomes following minimal invasive versus conventional aortic valve
      replacement: a propensity match analysis.
AB  - INTRODUCTION: Minimal invasive aortic valve replacement has become a routine
      procedure. In this study, we compared the outcomes between conventional and
      minimal invasive aortic valve replacement via the partial upper sternotomy that
      were performed in our Institution. METHODS: The 5 year survival and postoperative
      outcomes of 34 patients that underwent isolated MIAVR between the years 2010-2013
      were compared with the outcomes of 34 randomly selected patients that underwent
      conventional AVR, after propensity match analysis. RESULTS: There was no
      difference between the two groups concerning the early and late postoperative
      outcomes. MIAVR patients had a longer mean cross-clamp time (p = 0.002) and
      longer cardiopulmonary bypass time (p = 0.0005) compared to the AVR patients. 5
      year mortality and survival were 4.17 % vs 16.67 % (p = 0.20) and 95.8 % vs 83.3
      % (p = 0.37) in the MIAVR and AVR groups respectively. CONCLUSION: This study
      showed a comparable 5 year survival and postoperative outcomes between the MIAVR
      and AVR groups. In our opinion, the minimal access aortic valve replacement can
      be performed safely with excellent long-term results in selected patients (Tab.
      4, Fig. 1, Ref. 35).

PMID- 29050487
TI  - Use of graph algorithms in the processing and analysis of images with focus on
      the biomedical data.
AB  - INTRODUCTION: Image segmentation is a known problem in the field of image
      processing. A great number of methods based on different approaches to this issue
      was created. One of these approaches utilizes the findings of the graph theory.
      METHODS: Our work focuses on segmentation using shortest paths in a graph.
      Specifically, we deal with methods of "Intelligent Scissors," which use
      Dijkstra's algorithm to find the shortest paths. RESULTS: We created a new
      software in Microsoft Visual Studio 2013 integrated development environment
      Visual C++ in the language C++/CLI. We created a format application with a
      graphical users development environment for system Windows, with using the
      platform .Net (version 4.5). The program was used for handling and processing the
      original medical data. CONCLUSION: The major disadvantage of the method of
      "Intelligent Scissors" is the computational time length of Dijkstra's algorithm.
      However, after the implementation of a more efficient priority queue, this
      problem could be alleviated. The main advantage of this method we see in training
      that enables to adapt to a particular kind of edge, which we need to segment. The
      user involvement has a significant influence on the process of segmentation,
      which enormously aids to achieve high-quality results (Fig. 7, Ref. 13).

PMID- 29050488
TI  - Association between neutrophil/lymphocyte ratio with ductus arteriosus patency in
      preterm newborns.
AB  - OBJECTIVE: The aim of this study was to assess the influence of neutrophil to
      lymphocyte (N/L) ratio and platelet indices on patent ductus arteriosus (PDA) in
      preterm infants. BACKGROUND: PDA is a common problem with potentially serious
      associated morbidities in preterm neonates. METHODS: Premature infants with
      hemodynamically significant PDA (n = 47) and a control group without PDA (n = 50)
      who were hospitalized in the neonatal intensive care unit were retrospectively
      evaluated. The characteristics, perinatal factors, N/L ratio, platelet counts and
      other platelet indices of the infants in both groups during the first 3 days of
      life were recorded. RESULTS: Platelet counts were significantly lower in the
      patient group than in the control group (p = 0.0343). There was a marked positive
      correlation between body weight and N/L ratio in preterm infants with PDA (p =
      0.0001). PDA was associated with low platelet count. CONCLUSION: Our results
      showed that N/L ratio is positively correllated with body weight in PDA group.
      These data suggest that platelet counts and N/L ratio might be useful predictors
      for the early diagnosis and evaluation of the clinical course of PDA in preterm
      infants (Tab. 2, Ref. 28).

PMID- 29050489
TI  - Neutrophil-to-lymphocyte ratio in thyroid ophthalmopathy.
AB  - PURPOSE: To evaluate the neutrophil-to-lymphocyte ratio (NLR) levels to predict
      the severity of inflammation in thyroid ophthalmopathy (TO). METHODS: Fifty-six
      patients with TO and 40 healthy subjects were included in this study. TO patients
      were divided into two groups according to clinical activity score (CAS). Group 1
      included 24 active TO patients and Group 2 included 32 inactive TO patients. The
      thyroid status, white blood cell (WBC), neutrophil, and lymphocyte counts were
      performed. NLR was calculated by dividing the neutrophil count by the lymphocyte
      count. RESULTS: The mean age was 53.6 +/- 5.4 in active TO group, 54.2 +/- 5.6 in
      inactive TO group, and 52.7 +/- 5.2 in the control group. The WBC, neutrophil,
      lymphocyte and NLR levels were higher in patients with TO than in the control
      group (p < 0.05). A significant difference in NLR was found between the inactive
      and active TO groups (p < 0.05). CONCLUSION: NLR values were found to be higher
      in patients with TO than in controls. NLRvalues were also found higher in active
      TO patients than in inactive TO patients (Tab. 3, Ref. 26).

PMID- 29050490
TI  - MiR-26a regulates vascular smooth muscle cell calcification in vitro through
      targeting CTGF.
AB  - Vascular calcification is one of the most important factors for high morbidity
      and mortality from cardiovascular and cerebrovascular diseases. The aim of this
      study is to investigate the effect and mechanism of miR-26a on vascular smooth
      muscle cell calcification. First, the VSMCs were induced by beta-glycerol
      phosphate (beta-GP) for 7d and 14d, and Alizarin Red S staining was performed to
      examine the mineralized nodule change; then real time RT-PCR and western blotting
      were performed to explore the expression of miR-26a, CTGF, OPG, RANKL and ALP in
      un-induced and beta-GP-induced VSMCs; next, the VSMCs were transfected with miR
      26a mimics, and Alizarin Red S staining was performed to examine the mineralized
      nodule change; finally, real time RT-PCR and western blotting were performed to
      explore the expression of miR-26a, CTGF, OPG, RANKL and ALP in un-transfected and
      miR-26a mimics transfected VSMCs. After beta-GP treatment, beta-GP promoted clear
      mineralized nodule changes, and miR-26a and OPG expression were significantly
      decreased and CTGF, RANKL and ALP expression were increased in VSMCs.
      Overexpression of miR-26a inhibited VSMCs calcification induced by beta-GP, and
      regulated the expression of CTGF, OPG, RANKL and ALP. Our findings suggested that
      up-regulation of miR-26a before beta-GP treatment inhibits VSMCs calcification
      through targeting CTGF (Fig. 4, Ref. 18).

PMID- 29050491
TI  - Some antidiabetic medicinal plants used by traditional healers in Ado Ekiti,
      Nigeria.
AB  - OBJECTIVES: The work described plants collection, preparation and administration
      for diabetes cure in Ado Ekiti in Nigeria. METHODS: Twenty three plant samples
      were identified for the use in the treatment of diabetes by the herbalists. The
      plants that are common among the healers are Anthocleista djalonensis, Vernonia
      amygdalina, Ocimum gratissimum, Momordica charantia. RESULTS: The most preferred
      method of preparation by the healers is concoction and decoction of fresh leaves,
      stem bark and roots. However, for emergency sake, some healers dried these plant
      parts, ground to smooth powder and packaged in brown bottles or in nylon which
      are either sold or given to people, but must be soaked in cold or warm water
      before use. CONCLUSION: The use of medicinal plants in healing diabetes is a
      common practice by traditional healers in Ado Ekiti and never treat their
      patients in conjunction with modern medicines (Ref. 4).

PMID- 29050492
TI  - Prevalence of Dementia in a Geriatric Palliative Care Unit.
AB  - OBJECTIVES: To determine the prevalence of dementia in a palliative care unit
      (PCU) and to determine whether there is a difference between length of stay (LOS)
      and Palliative Performance Scale (PPS) score in individuals admitted with a
      primary diagnosis of dementia compared to individuals admitted with other
      noncancer and cancer diagnoses. DESIGN: Descriptive retrospective chart review.
      SETTING: Geriatric PCU in an academic community geriatric hospital. PARTICIPANTS:
      All individuals admitted to the Baycrest Health Sciences PCU from January 1,
      2014, to September 1, 2016. MEASUREMENTS: Individuals with an admission diagnosis
      of cancer, noncancer, and dementia and their corresponding PPS scores were
      identified. Data were analyzed using descriptive statistics. RESULTS: A total of
      780 patients were admitted to the PCU during the study period: 32 (4.1%)
      individuals had advanced dementia, 121 (15.5%) had a noncancer diagnosis, and 627
      (80.4%) had cancer as the primary reason for admission. In the cancer and
      noncancer groups, 113 patients had a comorbid dementia diagnosis. The mean
      admission PPS score in patients with cancer was 36%, noncancer was 32.6%, and
      dementia was 23.8% ( P < .001). Mean LOS in patients with cancer was 32 days,
      noncancer patients was 34.3 days, and patients with advanced dementia was 33.3
      days ( P = .90). CONCLUSIONS: Individuals with an admission diagnosis of advanced
      dementia had a lower mean PPS score than individuals admitted with other
      noncancer and cancer diagnoses. There was no difference in the mean LOS between
      the 3 groups. Individuals with an admission diagnosis of advanced dementia should
      not be refused admission because of fear of outliving their prognosis.

PMID- 29050493
TI  - Serum BDNF Is Positively Associated With Negative Symptoms in Older Adults With
      Schizophrenia.
AB  - OBJECTIVES: Older adults with chronic schizophrenia are at greater risk for
      functional disability and poorer health outcomes than those without serious
      mental illness. These individuals comprise 1-2% of the elderly population in the
      United States and are projected to number approximately 15 million by 2030. The
      symptoms of schizophrenia can be disabling for individuals, significantly
      reducing quality of life. Often, the negative symptoms (NS) are the most
      resistant to treatment and are considered a marker of illness severity, though
      they are challenging to measure objectively. Biomarkers can serve as objective
      indicators of health status. Brain-derived neurotrophic factor (BDNF) is a
      potential biomarker for schizophrenia and may serve as an important indicator of
      illness severity. METHODS: A cross-sectional study with 30 older adults with
      chronic schizophrenia. Participants were assessed on serum levels of BDNF and
      psychiatric symptoms (Positive and Negative Syndrome Scale). Pearson's bivariate
      correlations (two-tailed) and linear regression models were used. RESULTS: A
      significant positive association ( p < .05) was found between higher serum levels
      of BDNF and greater severity for the NS items of passive, apathetic, social
      withdrawal, and emotional withdrawal. In multivariate analyses, the association
      remained significant. CONCLUSIONS: Although the association between BDNF and NS
      was not in the expected direction, the data corroborate findings from previous
      work in patients with schizophrenia. It is possible that higher serum levels of
      BDNF reflect compensatory neuronal mechanisms resulting from neurodevelopmental
      dysfunction.

PMID- 29050494
TI  - Whole transcriptome analysis identifies differentially regulated networks between
      osteosarcoma and normal bone samples.
AB  - We performed whole transcriptome analysis of osteosarcoma bone samples.
      Initially, we sequenced total RNA from 36 fresh-frozen samples (18 tumoral bone
      samples and 18 non-tumoral paired samples) matching in pairs for each
      osteosarcoma patient. We also performed independent gene expression analysis of
      formalin-fixed paraffin-embedded samples to verify the RNAseq results. Formalin
      fixed paraffin-embedded samples allowed us to analyze the effect of chemotherapy.
      Data were analyzed with DESeq2, edgeR and Reactome packages of R. We found 5365
      genes expressed differentially between the normal bone and osteosarcoma tissues
      with an FDR below 0.05, of which 3399 genes were upregulated and 1966 were
      downregulated. Among those genes, BTNL9, MMP14, ABCA10, ACACB, COL11A1, and PKM2
      were expressed differentially with the highest significance between tumor and
      normal bone. Functional annotation with the reactome identified significant
      changes in the pathways related to the extracellular matrix degradation and
      collagen biosynthesis. It was suggested that chemotherapy may induce the
      modification of ECM with important collagen biosynthesis. Taken together, our
      results indicate that changes in the degradation of extracellular matrix seem to
      be an important mechanism of osteosarcoma and efficient chemotherapy induces the
      genes related to bone formation. Impact statement Osteosarcoma is a rare disease
      but it is of interest to many scientists all over the world because the current
      standard treatment still has poor results. We sequenced total RNA from 36 fresh
      frozen paired samples (18 tumoral bone samples and 18 non-tumoral paired samples)
      from osteosarcoma patients. We found that differences in the gene expressions
      between the normal and affected bones reflected the changes in the regulation of
      the degradation of collagen and extracellular matrix. We believe that these
      findings contribute to the understanding of OS and suggest ideas for further
      studies.

PMID- 29050495
TI  - Modeling the pressure inactivation of Escherichia coli and Salmonella typhimurium
      in sapote mamey ( Pouteria sapota (Jacq.) H.E. Moore & Stearn) pulp.
AB  - High hydrostatic pressure inactivation kinetics of Escherichia coli ATCC 25922
      and Salmonella enterica subsp. enterica serovar Typhimurium ATCC 14028 ( S.
      typhimurium) in a low acid mamey pulp at four pressure levels (300, 350, 400, and
      450 MPa), different exposure times (0-8 min), and temperature of 25 +/- 2C were
      obtained. Survival curves showed deviations from linearity in the form of a tail
      (upward concavity). The primary models tested were the Weibull model, the
      modified Gompertz equation, and the biphasic model. The Weibull model gave the
      best goodness of fit ( R2adj > 0.956, root mean square error < 0.290) in the
      modeling and the lowest Akaike information criterion value. Exponential-logistic
      and exponential decay models, and Bigelow-type and an empirical models for b'( P)
      and n( P) parameters, respectively, were tested as alternative secondary models.
      The process validation considered the two- and one-step nonlinear regressions for
      making predictions of the survival fraction; both regression types provided an
      adequate goodness of fit and the one-step nonlinear regression clearly reduced
      fitting errors. The best candidate model according to the Akaike theory
      information, with better accuracy and more reliable predictions was the Weibull
      model integrated by the exponential-logistic and exponential decay secondary
      models as a function of time and pressure (two-step procedure) or incorporated as
      one equation (one-step procedure). Both mathematical expressions were used to
      determine the td parameter, where the desired reductions ( 5D) (considering d = 5
      ( t5) as the criterion of 5 Log10 reduction (5 D)) in both microorganisms are
      attainable at 400 MPa for 5.487 +/- 0.488 or 5.950 +/- 0.329 min, respectively,
      for the one- or two-step nonlinear procedure.

PMID- 29050496
TI  - Investigation of bio-oil produced by hydrothermal liquefaction of food waste
      using ultrahigh resolution Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Recent research has revealed that more than 1.3 billion tons of food is wasted
      globally every year. The disposal of such huge biomass has become a challenge. In
      the present paper, we report the production of the bio-oil by hydrothermal
      liquefaction of three classes of food waste: meat, cheese and fruits. The highest
      yield of the bio-oil was observed for meat (~60%) and cheese (~75%), while for
      fruits, it was considerably low (~10%). The molecular composition of the obtained
      bio-oil was investigated using ultrahigh resolution Fourier Transform Ion
      Cyclotron Resonance mass spectrometry and was found to be similar to that
      obtained from algae. Several thousand heteroatom compounds (N, N2, ON2, etc.
      classes) were reliably identified from each sample. It was found that bio-oils
      produced from meat and cheese have many compounds (~90%) with common molecular
      formulas, while bio-oil produced from fruits differs considerably (~30% of
      compounds are unique).

PMID- 29050497
TI  - Simoctocog alfa for the treatment of hemophilia A.
AB  - INTRODUCTION: Hemophilia A is the most frequent inherited bleeding disorder and
      most challenging coagulation disorder. To combat this, a number of new improved
      rFVIII/IX concentrates have recently been approved. Some of them are derived from
      protein fusion biotechnology or pegylation to extend their half-life (HL).
      However, prophylaxis has become a standard of care to prevent arthropathy in
      hemophiliacs though the need of frequent venipunctures is a major obstacle to
      primary prophylaxis. The new Extended Half-Life (EHL) rFIX concentrates allow
      increased intervals, while the improved HL of new rFVIII was moderate. rFVIII
      Simoctocog alfa is produced in Human Embryonic Kidney (HEK) cells and the post
      translational modifications performed by HEK cells are very similar to those
      occurring in the native FVIII. Areas covered: Herein, the author provides a
      review of simoctocog alfa with its contents including information on simoctocog
      alfa's manufacturing, clinical trials, safety and tolerability. They also give
      their expert opinion and future perspectives on this therapy. Expert opinion: An
      important advantage of simoctocog alfa is the possibility to omit at least 30% of
      venipunctures with prophylaxis. Consequently, the standard three times weekly
      bolus administrations may be reduced to twice weekly, meaning approximately 50
      fewer venipunctures per year. This may be particularly helpful to children.

PMID- 29050498
TI  - Complete detoxification is the most effective treatment of medication-overuse
      headache: A randomized controlled open-label trial.
AB  - Background There is lack of evidence on how to detoxify medication-overuse
      headache. Aim To compare the effect of complete stop of acute medication with
      restricted intake. Methods Medication-overuse headache patients were included in
      a prospective, outpatient study and randomized to two months' detoxification with
      either a) no analgesics or acute migraine-medication (program A), or b) acute
      medication restricted to two days/week (program B). Detoxification was followed
      by preventives if indicated. Patients were followed up at 2, 6 and 12 months.
      Percentage reduction in headache days/month after 6 months was the primary
      outcome. Results We included 72 medication-overuse headache patients with a
      primary migraine and/or tension-type headache diagnosis. Fifty-nine completed
      detoxification, 58 (81%) were followed up at month 6 and 53 (74%) at month 12. At
      month 6, program A reduced headache days/month by 46% (95% CI 34-58) compared
      with 22% (95% CI 11-34) in program-B ( p = 0.005), and 70% in program A versus
      42% in program B were reverted to episodic headache ( p = 0.04). Migraine
      days/month were reduced by 7.2 in program A ( p < 0.001) and 3.6 in program B ( p
      = 0.002) after 6 months. Conclusion Both detoxification programs were very
      effective. Detoxification without analgesics or acute migraine-medication was the
      most effective program. Trial registration Clinicaltrials.gov (NCT02903329).

PMID- 29050499
TI  - Congenital Factor Deficiencies in Children: A Report of a Single-Center
      Experience.
AB  - Congenital factor deficiencies (CFDs) refer to inherited deficiency of
      coagulation factors in the blood. A total of 481 patients with CFDs, who were
      diagnosed and followed at our Pediatric Hematology and Oncology Clinic between
      1990 and 2015, were retrospectively evaluated. Of the 481 cases, 134 (27.8%) were
      hemophilia A, 38 (7.9%) were hemophilia B, 57 (11.8%) were von Willebrand disease
      (vWD), and 252 (52.3%) were rare bleeding disorders (RBDs). The median age of the
      patients at the time of diagnosis and at the time of the study was 4.1 years
      (range: 2 months to 20.4 years) and 13.4 years (range: 7 months to 31.3 years),
      respectively. The median duration of the follow-up time was 6.8 years (range: 2.5
      months to 24.8 years). One hundred nineteen (47.2%) of 252 patients with RBDs
      were asymptomatic, 49 (41.1%) of whom diagnosed by family histories, 65 (54.6%)
      through preoperative laboratory studies, and 5 (4.2%) after prolonged bleeding
      during surgeries. Consanguinity rate for the RBDs was 47.2%. Prophylactic
      treatment was initiated in 80 patients, 58 of whom were hemophilia A, 7 were
      hemophilia B, 13 were RBDs, and 2 were vWD. Significant advances have been
      achieved during the past 2 decades in the treatment of patients with CFDs,
      particularly in patients with hemophilias. The rarity and clinical heterogeneity
      of RBDs lead to significant diagnostic challenges and improper management. In
      this regard, multinational collaborative efforts are needed with the hope that
      can improve the management of patients with RBDs.

PMID- 29050500
TI  - Prophylactic Fibrinogen Decreases Postoperative Bleeding but Not Acute Kidney
      Injury in Patients Undergoing Heart Transplantation.
AB  - The present study is the premier clinical attempt to scrutinize the
      practicability of prophylactic fibrinogen infusion in patients undergoing heart
      transplantation (HT). A total of 67 consecutive patients who had undergone HT
      between January 2012 and December 2014 were assessed. After exclusion of some
      patients, 23 patients were given preoperative 2 g fibrinogen concentrate over a
      period of 15 minutes after the termination of cardiopulmonary bypass pump and
      complete reversal of heparin, and 30 patients were not given. Some laboratories
      were measured before general anesthesia and at 6 and 24 hours after surgery. In
      addition, major adverse events were also evaluated during hospitalization. The
      mean age of the patients was 39.5 +/- 11.4 years, with a predominance of male sex
      (77.4%). All laboratories at baseline were comparable between groups. The length
      of hospital stay was longer in the control group compared to the fibrinogen group
      (20 [16-22] vs 16 [12-19] days; P = .005). There was a trend for patients in the
      fibrinogen group to have more acute kidney injury (AKI) after surgery (10% vs
      30.4%) and less reoperation for bleeding (20% vs 8.7%). The amount of
      postoperative bleeding was significantly higher in the control group compared to
      the fibrinogen group ( P < .001). The number of packed red blood cell transfused
      during 24 hours after surgery was significantly lower in the fibrinogen group ( P
      < .001). The transfusion of fibrinogen in patients undergoing HT may be
      associated with reductions in postoperative bleeding, the number of packed red
      blood cells, and hospital length of stay; however, it may enhance postoperative
      AKI.

PMID- 29050501
TI  - Platelet Activation Assessed by Glycoprotein VI/Platelet Ratio Is Associated With
      Portal Vein Thrombosis After Hepatectomy and Splenectomy in Patients With Liver
      Cirrhosis.
AB  - Portal vein thrombosis (PVT) is a serious complication after hepatobiliary
      pancreatic surgery. Portal vein thrombosis often develops in patients with liver
      cirrhosis (LC) postoperatively, although they have low platelet counts. Platelet
      activation is one of the causes of thrombosis formation, and soluble form of
      glycoprotein VI (sGPVI) has received attention as a platelet activation marker.
      We had prospectively enrolled the 81 consecutive patients who underwent
      splenectomy (Sx) and/or hepatectomy: these patients were divided as Sx (n = 38)
      and hepatectomy (Hx, n = 46) groups. The 3 patients who underwent both procedures
      were added to both groups. Each group was subdivided into patients with non-LC
      and LC: non-LC-Sx (n = 22) and LC-Sx (n = 16), non-LC-Hx (n = 40) and LC-Hx (n =
      6). The presence of PVT was diagnosed by using enhanced computed tomography (CT)
      scan. Platelet counts were significantly lower in LC-Sx than in non-LC-Sx, and
      incidence of PVT was significantly higher in LC-Sx than in non-LC-Sx (68.8% vs
      31.8%, P = .024). Soluble form of glycoprotein VI /platelet ratios on
      preoperative day and postoperative day 1 were significantly higher in LC-Sx than
      in non-LC-Sx. Incidence of PVT was significantly higher in LC-Hx than in non-LC
      Hx (50.0% vs 7.5%, P < .01). Soluble form of glycoprotein VI /platelet ratios
      were significantly higher in LC-Hx before and after Hx, compared to non-LC-Hx.
      Patients with LC stay in hypercoagulable state together with platelet activation
      before and after surgery. Under this circumstance, alteration of portal venous
      blood flow after Sx or Hx is likely to cause PVT in patients with LC.

PMID- 29050502
TI  - First Evidence: TRAP-Induced Platelet Aggregation Is Reduced in Patients
      Receiving Xabans.
AB  - The availability of direct oral anticoagulants has caused a paradigm shift in the
      management of thrombosis. Rivaroxaban and apixaban are 2 direct oral
      anticoagulants whose target specificity is activated factor X (FXa). However, it
      is still not fully understood if and how xabans impact platelet function. This
      observational study aimed to assess the in vitro platelet function in patients
      with atrial fibrillation receiving xabans. This was a single-center study
      quantifying platelet aggregation in 41 patients treated with apixaban or
      rivaroxaban by light transmission aggregometry. The thrombin receptor activating
      peptide (TRAP)-induced platelet aggregation was significantly lower 2 hours after
      taking rivaroxaban or apixaban compared to baseline value (56.15% [8.53%] vs
      29.51% [12.9%]; P = .000). Moreover, concomitant use of angiotensin-converting
      enzyme blockers, proton pump inhibitors, and statins reduces the efficiency of
      xabans. The TRAP-induced platelet aggregation was reduced in patients with
      cardiovascular disease 2 hours after receiving xabans.

PMID- 29050503
TI  - Reticulated platelets in poorly controlled diabetes: A new era in the management
      of residual risk?

PMID- 29050504
TI  - Transgender Research in the 21st Century: A Selective Critical Review From a
      Neurocognitive Perspective.
AB  - Gender dysphoria describes the psychological distress caused by identifying with
      the sex opposite to the one assigned at birth. In recent years, much progress has
      been made in characterizing the needs of transgender persons wishing to
      transition to their preferred gender, thus helping to optimize care. This
      critical review of the literature examines their common mental health issues,
      several individual risk factors for psychiatric comorbidity, and current research
      on the underlying neurobiology. Prevalence rates of persons identifying as
      transgender and seeking help with transition have been rising steeply since 2000
      across Western countries; the current U.S. estimate is 0.6%. Anxiety and
      depression are frequently observed both before and after transition, although
      there is some decrease afterward. Recent research has identified autistic traits
      in some transgender persons. Forty percent of transgender persons endorse
      suicidality, and the rate of self-injurious behavior and suicide are markedly
      higher than in the general population. Individual factors contributing to mental
      health in transgender persons include community attitudes, societal acceptance,
      and posttransition physical attractiveness. Neurobiologically, whereas structural
      MRI data are thus far inconsistent, functional MRI evidence in trans persons
      suggests changes in some brain areas concerned with olfaction and voice
      perception consistent with sexual identification, but here too, a definitive
      picture has yet to emerge. Mental health clinicians, together with other health
      specialists, have an increasing role in the assessment and treatment of gender
      dysphoria in transgender individuals.

PMID- 29050506
TI  - Comparing Strategies for Health Information Dissemination: Messengers That Can
      Help or Hinder.
AB  - PURPOSE: To test the effects of different messengers on the dissemination of
      health information. DESIGN: An experimental study exposed participants to 12 news
      articles pertaining to 1 of 3 health topics framed from the perspective of 4
      generic messengers: religious figures, doctors, celebrity patients, or ordinary
      patients. Participants select as many of the 12 articles as desired. SETTING: A
      cancer clinic within a large, urban hospital serving a sociodemographically
      diverse patient population. PARTICIPANTS: Eighty-nine patients with a history of
      cancer. MEASURES: The primary outcome was the frequency with which each news
      story was selected. ANALYSIS: Summary statistics and a general estimating
      equation model. RESULTS: For each health topic, news articles using celebrity
      messengers were the least likely to be selected; almost half of the participants
      (36 [41.4%] of 87) rejected all such articles. Articles linked to religious
      figures were equally unpopular ( P = .59). Articles that used doctors or ordinary
      patients as the messenger were very likely to be selected: Nearly all women (84
      [96.6%] of 87) selected at least one of these. Furthermore, the odds of choosing
      articles linked to celebrities or religious leaders were statistically
      significantly lower than the odds of choosing those linked to ordinary patients
      or doctors ( P < .01). CONCLUSION: Commonly used generic messengers had large
      effects on the dissemination of information. Health materials linked to
      celebrities or religious figures were consistently less likely to be selected
      than those linked to ordinary patients, or doctors.

PMID- 29050505
TI  - Late-Onset ADHD Reconsidered With Comprehensive Repeated Assessments Between Ages
      10 and 25.
AB  - OBJECTIVE: Adolescents and young adults without childhood attention deficit
      hyperactivity disorder (ADHD) often present to clinics seeking stimulant
      medication for late-onset ADHD symptoms. Recent birth-cohort studies support the
      notion of late-onset ADHD, but these investigations are limited by relying on
      screening instruments to assess ADHD, not considering alternative causes of
      symptoms, or failing to obtain complete psychiatric histories. The authors
      address these limitations by examining psychiatric assessments administered
      longitudinally to the local normative comparison group of the Multimodal
      Treatment Study of ADHD. METHOD: Individuals without childhood ADHD (N=239) were
      administered eight assessments from comparison baseline (mean age=9.89 years) to
      young adulthood (mean age=24.40 years). Diagnostic procedures utilized parent,
      teacher, and self-reports of ADHD symptoms, impairment, substance use, and other
      mental disorders, with consideration of symptom context and timing. RESULTS:
      Approximately 95% of individuals who initially screened positive on symptom
      checklists were excluded from late-onset ADHD diagnosis. Among individuals with
      impairing late-onset ADHD symptoms, the most common reason for diagnostic
      exclusion was symptoms or impairment occurring exclusively in the context of
      heavy substance use. Most late-onset cases displayed onset in adolescence and an
      adolescence-limited presentation. There was no evidence for adult-onset ADHD
      independent of a complex psychiatric history. CONCLUSIONS: Individuals seeking
      treatment for late-onset ADHD may be valid cases; however, more commonly,
      symptoms represent nonimpairing cognitive fluctuations, a comorbid disorder, or
      the cognitive effects of substance use. False positive late-onset ADHD cases are
      common without careful assessment. Clinicians should carefully assess impairment,
      psychiatric history, and substance use before treating potential late-onset
      cases.

PMID- 29050507
TI  - Effectiveness of an overall progressive resistance strength program for improving
      the functional capacity of patients with rheumatoid arthritis: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of overall progressive resistance
      training in patients with rheumatoid arthritis. DESIGN: Randomized controlled
      clinical trial with blinded assessor and intention-to-treat analysis. SETTING:
      Outpatient clinics. SUBJECTS: Sixty patients with rheumatoid arthritis according
      to the American College of Rheumatology criteria, aged between 18 and 65 years
      old, under stable medication and not performing regular physical activity were
      randomized into two groups: intervention group (IG) and control group (CG).
      INTERVENTIONS: IG performed the progressive resistance strength training, twice a
      week, during 12 weeks. The training consists of exercising various muscle groups
      using a load of 50% and 70% of one repetition maximum. The load was reassessed
      and adjusted after six weeks of baseline. Both groups remained in conventional
      drug treatment during the study. MAIN MEASURES: Patients were evaluated at
      baseline and after 6, 12, and 24 weeks, using HAQ and SF-36 questionnaires and
      strength. RESULTS: Thirty-three patients in the CG and 27 in the IG were
      evaluated. The groups were homogeneous at baseline. Statistical and clinical
      improvement were found with better results for the IG in the HAQ questionnaire (
      P=0.030), functional capacity (0=0.022) and pain ( P=0.027) domains of SF-36; and
      muscle strength for flexors of right and left knee ( P=0.005 and p=0.14),
      abductors of shoulder ( P=0.041) and extensors of right and left wrists ( P=0.003
      and P= 0.005). CONCLUSIONS: This progressive resistance strength training
      improves physical function as well as grip and muscular strength of knee flexors,
      shoulder abductors and wrist extensors in patients with RA, without adverse
      effects.

PMID- 29050508
TI  - 'Doing with ...' rather than 'doing for ...' older adults: rationale and content
      of the 'Stay Active at Home' programme.
AB  - BACKGROUND: Owing to increasing age, accidents or periods of illness, home care
      services are provided to community-dwelling older adults. Traditionally, these
      services focus on doing things for older adults rather than with them; though
      from a rehabilitative perspective, it is important to assist older adults to
      attain and maintain their highest level of functioning. Consequently, a re
      orientation of home care services is required away from treating disease and
      creating dependency towards focusing on capabilities and opportunities and
      maximising independence. To achieve this behavioural change in home care
      professionals, the 'Stay Active at Home' programme was developed. AIMS AND
      METHODS: The aim of this article is to give a detailed description of the
      rationale and content of the 'Stay Active at Home' programme by making use of the
      TIDieR (Template for Intervention Description and Replication) Checklist.
      APPROACH: 'Stay Active at Home' is a comprehensive training programme that aims
      to equip home care professionals (i.e. community nurses and domestic support
      workers) with the necessary knowledge, attitude, skills and social and
      organisational support to deliver day-to-day services at home from a more
      rehabilitative perspective. More specifically, home care professionals are
      expected to deliver goal-oriented, holistic and person-centred services focusing
      on supporting older adults to maintain, gain or restore their competences to
      engage in physical and daily activities so that they can manage their everyday
      life as independently as possible.

PMID- 29050509
TI  - Introductory paragraph.

PMID- 29050510
TI  - Effects of yoga on chronic neck pain: a systematic review and meta-analysis.
AB  - OBJECTIVE: The aim of this review was to systematically assess and meta-analyze
      the effectiveness of yoga in relieving chronic neck pain. METHODS:
      PubMed/MEDLINE, the Cochrane Library, Scopus, and IndMED were screened through
      January 2017 for randomized controlled trials assessing neck pain intensity
      and/or neck pain-related disability in chronic neck pain patients. Secondary
      outcome measures included quality of life, mood, and safety. Risk of bias was
      assessed using the Cochrane tool. RESULTS: Three studies on 188 patients with
      chronic non-specific neck pain comparing yoga to usual care were included. Two
      studies had overall low risk of bias; and one had high or unclear risk of bias
      for several domains. Evidence for short-term effects was found for neck pain
      intensity (standardized mean difference (SMD) = -1.28; 95% confidence interval
      (CI) = -1.18, -0.75; P < 0.001), neck pain-related disability (SMD = -0.97; 95%
      CI = -1.44, -0.50; P < 0.001), quality of life (SMD = 0.57; 95% CI = 0.17, 0.197;
      P = 0.005), and mood (SMD = -1.02; 95% CI = -1.38, -0.65; P < 0.001). Effects
      were robust against potential methodological bias and did not differ between
      different intervention subgroups. In the two studies that included safety data,
      no serious adverse events occurred. CONCLUSION: Yoga has short-term effects on
      chronic neck pain, its related disability, quality of life, and mood suggesting
      that yoga might be a good treatment option.

PMID- 29050511
TI  - Efficacy of constraint-induced movement therapy compared with bimanual intensive
      training in children with unilateral cerebral palsy: a systematic review.
AB  - OBJECTIVE: To systematically review the evidence on the effect of constraint
      induced movement therapy compared with bimanual intensive training in children
      with unilateral cerebral palsy. DATA SOURCES: Seven electronic databases (Cinahl,
      Cochrane Library, EMBASE, Ovid MEDLINE, PEDro, PsycINFO, PubMed) were searched
      from database inception through December 2016. METHODS: A systematic review was
      performed using the American Academy of Cerebral Palsy and Developmental Medicine
      and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.
      Standardised mean differences (effect sizes) were calculated for each study and
      outcome. RESULTS: Nine studies met the eligibility criteria. All studies provided
      level II evidence. Methodological quality was high in two studies, moderate in
      four studies and low in three studies. The methodology, participant and
      intervention characteristics were heterogeneous. The participants' ages ranged
      from 1.5 to 16 years. Their initial hand function ranged from Manual Ability
      Classification System Level I to Level III. The total intervention dose ranged
      from 24 to 210 hours and duration from one week to ten weeks. The studies
      measured outcomes assessing unimanual and bimanual hand and arm function,
      participation and attainment of individualised goals. Overall, the effect sizes
      did not favour one of the interventions at short- or long-term follow-up. The 95%
      confidence intervals were broad, indicating inaccurate precision of the effect
      sizes. Pooling of the data for a meta-analysis was judged to be of little
      clinical value owing to heterogeneity. CONCLUSION: It is not possible to conclude
      whether constraint-induced movement therapy or bimanual intensive training is
      more effective than the other in children with unilateral cerebral palsy.

PMID- 29050512
TI  - Iron deficiency beyond erythropoiesis: should we be concerned?
AB  - OBJECTIVE: To consider the key implications of iron deficiency for biochemical
      and physiological functions beyond erythropoiesis. METHODS: PubMed was searched
      for relevant journal articles published up to August 2017. RESULTS: Anemia is the
      most well-recognized consequence of persisting iron deficiency, but various other
      unfavorable consequences can develop either before or concurrently with anemia.
      Mitochondrial function can be profoundly disturbed since iron is a cofactor for
      heme-containing enzymes and non-heme iron-containing enzymes in the mitochondrial
      electron transport chain. Biosynthesis of heme and iron-sulfur clusters in the
      mitochondria is inhibited, disrupting synthesis of compounds such as hemoglobin,
      myoglobin, cytochromes and nitric oxide synthase. The physiological consequences
      include fatigue, lethargy, and dyspnea; conversely, iron repletion in iron
      deficient individuals has been shown to improve exercise capacity. The
      myocardium, with its high energy demands, is particularly at risk from the
      effects of iron deficiency. Randomized trials have found striking improvements in
      disease severity in anemic but also non-anemic chronic heart failure patients
      with iron deficiency after iron therapy. In vitro and pre-clinical studies have
      demonstrated that iron is required by numerous enzymes involved in DNA
      replication and repair, and for normal cell cycle regulation. Iron is also
      critical for immune cell growth, proliferation, and differentiation, and for
      specific cell-mediated effector pathways. Observational studies have shown that
      iron-deficient individuals have defective immune function, particularly T-cell
      immunity, but more evidence is required. Pre-clinical models have demonstrated
      abnormal myelogenesis, brain cell metabolism, neurotransmission, and hippocampal
      formation in iron-deficient neonates and young animals. In humans, iron
      deficiency anemia is associated with poorer cognitive and motor skills. However,
      the impact of iron deficiency without anemia is less clear. CONCLUSION: The
      widespread cellular and physiological effects of iron deficiency highlight the
      need for early detection and treatment of iron deficiency, both to ameliorate
      these non-erythropoietic effects, and to avoid progression to iron deficiency
      anemia.

PMID- 29050513
TI  - CE-MS-based metabolomics reveals the metabolic profile of maitake mushroom
      (Grifola frondosa) strains with different cultivation characteristics.
AB  - Maitake mushroom (Grifola frondosa [Dicks.] Gray) is generally cultured using the
      sawdust of broadleaf trees. The maitake strain Gf433 has high production
      efficiency, with high-quality of fruiting bodies even when 30% of the birch
      sawdust on the basal substrate is replaced with conifer sawdust. We performed
      metabolome analysis to investigate the effect of different cultivation components
      on the metabolism of Gf433 and Mori52 by performing CE-MS on their fruiting
      bodies in different cultivation conditions to quantify the levels of amino acids,
      organic acids, and phosphorylated organic acids. We found that amino acid and
      organic acid content in Gf433 were not affected by the kind of sawdust. However,
      Gf433 contained more organic acids and less amino acids than Mori52, and Gf433
      also contained more chitin compared with Mori52. We believe that these
      differences in the metabolome contents of the two strains are related to the high
      production efficiency of Gf433.

PMID- 29050514
TI  - Modelling self-assessed vulnerability to HIV and its associated factors in a HIV
      burdened country.
AB  - BACKGROUND: Globally, individuals' self-assessment of vulnerability to HIV
      infection is important to maintain safer sexual behaviour and reduce risky
      behaviours. However, determinants of self-perceived risk of HIV infection are not
      well documented and differ. We assessed the level of self-perceived vulnerability
      to HIV infection in Nigeria and also identified its risk factors. METHODS: We
      explored a recent nationally representative data with self-reported vulnerability
      ('high', 'low' and 'no risk at all') to HIV infection as the outcome of interest.
      Data were weighted and association between the outcomes and the risk factors
      determined. We used simple ordered logit regression to model relationship between
      the outcome variable and risk factors, and controlled for the significant
      variables in multiple ordered logistic regression at 5% significance level.
      RESULTS: About 74% had good knowledge of HIV transmission and 6% had experienced
      STI recently. The likelihood of assessing oneself as having 'no risk at all' was
      50% and for 'high chances' was 1.6%. Self-perceived high risk of HIV was higher
      among those who recently experienced STI (5.6%) than those who did not (1.7%),
      and also higher among those who recently engaged in transactional sex and had
      multiple sexual partners. The odds of good knowledge of HIV transmission on high
      self-perceived vulnerability to HIV was 19% higher than poor knowledge (OR =
      1.19, 95% CI: 1.12-1.27). Also, respondents who recently had multiple sexual
      partners were 72% (OR = 1.72, 95% CI: 1.60-1.86) more likely to report self as
      having high risk. Younger respondents aged 14-19 years had higher odds of 41% (OR
      = 1.41, 95% CI: 1.29-1.55) to perceive self as having high vulnerability to HIV
      than older respondents. CONCLUSION: High vulnerability to HIV infection was
      reported among younger respondents, those with history of STIS and those who
      engage in multiple sexual relations. Despite high level of risky sexual behaviour
      and good knowledge of HIV transmission and prevention found in this study, self
      perceived vulnerability to HIV generally is low. For the low perception found in
      this study to translate to low chance of HIV infection, there is need for all
      stakeholders to embark on risk reduction initiatives through sexual education
      that would minimise risky sexual practices and ensuring availability and
      affordability of HIV prevention methods.

PMID- 29050515
TI  - Cytologic and Ultrastructural Findings of Bronchoalveolar Lavage in Patients With
      Chronic Granulomatous Disease.
AB  - Background Chronic granulomatous disease (CGD) is a hereditary immunodeficiency
      caused by mutations in genes encoding nicotinamide adenine dinucleotide phosphate
      oxidase enzyme complex, which lead to the inability to kill intracellular
      pathogens. Patients with CGD are susceptible to recurrent bacterial and fungal
      infections in their early lives. Although the recent survival rate has been
      significantly improved, early diagnosis is critical to prevent multiple organ
      impairment. In 1950s, CGD was first described as a disease with recurrent
      infections and visceral infiltration of granulomas and pigmented histiocytes.
      Bronchoalveolar lavage (BAL) is commonly performed for patients with CGD;
      however, no study has described the cytologic features of alveolar macrophages.
      Methods Cytology of 20 BALs from 11 CGD patients was examined. The greatest
      diameters of randomly selected 100 alveolar macrophages in each BAL were measured
      using image analysis and compared with 20 disease control BALs from non-CGD
      patients. Macrophages from 2 groups were compared with repeated measures mixed
      model analysis. Ultrastructural analysis was performed on a representative CGD
      BAL. Results BALs from CGD patients showed variable numbers of neutrophils and
      lipid-laden macrophages. Macrophages in CGD BALs were significantly larger than
      disease control BALs ( P < .0001) and showed "foamy" vacuolated cytoplasm.
      Ultrastructural analysis revealed the macrophages filled with enlarged lysosomes
      containing lipofuscin-like materials, which made their appearance "foamy."
      Conclusion In this study, we demonstrate novel BAL findings in CGD patients. The
      presence of enlarged "foamy" alveolar macrophages is not specific for CGD, but
      CGD should be considered as a differential diagnosis when foamy macrophages are
      present.

PMID- 29050516
TI  - Human Bone Marrow Mesenchymal Stromal Cell-Derived Osteoblasts Promote the
      Expansion of Hematopoietic Progenitors Through Beta-Catenin and Notch Signaling
      Pathways.
AB  - Coculture of hematopoietic stem cells (HSC) with primary stromal cells from HSC
      niches supports the maintenance and expansion of HSC and progenitors ex vivo.
      However, a major drawback is the availability of primary human samples for
      research and clinical applications. We investigated the use of in vitro derived
      osteoblasts as a new source of feeder cells and characterized the molecular
      pathways that mediate their growth-promoting activities. First, we compared the
      growth and differentiation modulating activities of mesenchymal stromal cells
      (MSC)-derived osteoblasts (M-OST) with those of their undifferentiated precursor
      on umbilical cord blood (UCB) progenitors. Feeder-free cultures were also
      included as baseline control. Cell growth and expansion of hematopoietic
      progenitors were significantly enhanced by both feeder cell types. However,
      progenitor cell growth was considerably greater with M-OST. Coculture also
      promoted the maintenance of immature CD34+ progenitor subsets and modulated in a
      positive fashion the expression of several homing-related cell surface receptors,
      in a feeder-specific fashion. Serial transplantation experiments revealed that M
      OST coculture supported the maintenance of long-term lympho-myeloid
      reconstituting HSC that provided engraftment levels that were generally superior
      to those from MSC cocultures. Mechanistically, we found that coculture with M-OST
      was associated with enhanced beta-catenin (beta-Cat) activity in UCB cells and
      that abrogation of beta-Cat/T-cell factor activity blunted the growth-promoting
      activity of the M-OST coculture. Conversely, Notch inhibition reduced UCB cell
      expansion, but to a much lesser extent. In conclusion, this study demonstrates
      that M-OST are excellent feeder cells for HSC and progenitors, and it identifies
      key molecular pathways that are responsible for the growth-enhancing activities
      of osteoblasts on UCB progenitors.

PMID- 29050517
TI  - The safety and efficacy of dabrafenib and trametinib for the treatment of
      melanoma.
AB  - INTRODUCTION: The introduction of BRAF and MEK inhibitors into clinical practice
      improved the prognosis of metastatic melanoma patients. The combination of BRAF
      inhibitor dabrafenib with MEK inhibitor trametinib has shown its superiority to
      single agent therapy and is characterized by a tolerable spectrum of adverse
      events which shows a decrease in incidence over time on treatment. Areas covered:
      The current scientific literature on safety and adverse events (AEs) related to
      BRAF and MEK-inhibition has been investigated with special focus on the large
      phase 3 studies (COMBI-v, COMBI-d and CoBRIM) as well as recent updates presented
      at oncology and melanoma meetings. Additionally, published case series/case
      reports were screened for information on AEs. Expert opinion: Even though almost
      every patient (98%) under combination therapy with dabrafenib and trametinib
      experiences at least one adverse event, these are generally mild to moderate,
      reversible and can be managed with dose reductions or interruptions. However, due
      to an increased life expectancy, there is a substantial need to prevent and treat
      also mild adverse events, as they play a central role for the quality of life of
      patients. Ongoing clinical trials will have to demonstrate the efficacy as well
      as safety of triple combination with anti-PD-1/anti-PD-L1 antibodies.

PMID- 29050518
TI  - Naming speed as a predictive diagnostic measure in reading and attentional
      problems.
AB  - This study aimed to describe and compare naming speed abilities in children
      diagnosed with either Reading Learning Difficulties (RLD) or Attention
      Deficit/Hyperactivity Disorder (ADHD), or comorbidity for both (ADHD+RLD). To
      examine the explanatory power of naming speed and ADHD symptomatology in
      predicting group associations (while controlling for gender and age), the "Rapid
      Automatized Naming and Rapid Alternating Stimulus Tests" (RAN/RAS) were utilized.
      A sample of 101 children (age range = 5-16 years) was divided into four groups:
      RLD (n = 14), ADHD (n = 28), comorbid (n = 19), and control (n = 40). There were
      statistically significant differences in RAN/RAS results among the diagnostic
      groups. Moreover, discriminant analysis revealed that naming speed tasks
      significantly predicted reading and attentional problems, especially at earlier
      ages. These results demonstrate the potential usefulness of RAN/RAS in the
      diagnosis of reading and attentional problems, particularly if the children are
      aged from 5 to 9.

PMID- 29050519
TI  - LncRNA PVT1 predicts prognosis and regulates tumor growth in prostate cancer.
AB  - Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1(PVT1) was
      aberrantly expressed in various cancers and is associated with tumor prognosis.
      Here, we aim to investigate its function in prostate cancer. Small interfering
      RNA against PVT1 was transfected into prostate cancer cell lines and cell growth
      and apoptosis were analyzed. Our results showed that PVT1 was overexpressed in
      prostate cancer tissues and cells. Higher levels of PVT1 indicated poorer overall
      survival and disease-free survival. A significant association was found between
      PVT1 expression and tumor stage. Besides, PVT1 knockdown significantly inhibited
      prostate cancer growth in vivo and in vitro and promoted cell apoptosis. PVT1
      knockdown also significantly upregulated the expression of cleaved caspase-3 and
      cleaved caspase-9, but downregulated the expression of c-Myc in prostate cancer
      cell lines. Our results suggest that PVT1 played an oncogenic role in prostate
      cancer and could be used as a potential biomarker for diagnosis of prostate
      cancer.

PMID- 29050520
TI  - Evaluation of the pharmacokinetics, tissue distribution and excretion studies of
      YMR-65, a tubulin polymerization inhibitor with potential anticancer activity, in
      rats using UPLC-MS/MS.
AB  - 1. YMR-65, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H
      pyrazole-1-carboxamide, is a new tubulin polymerization inhibitor with
      encouraging anticancer activity. 2. The validated ultra-performance liquid
      chromatography-tandem mass spectrometer (UPLC-MS/MS) method was successfully
      applied to the pharmacokinetics, tissue distribution and excretion study of YMR
      65 after oral and intravenous administration. The area under concentration-time
      curve (AUC0-infinity) for YMR-65 were 151.67 +/- 54.48 and 459.45 +/- 49.23
      ng/ml*h for oral and intravenous administration at the dosage of 1.5 mg/kg,
      respectively and the oral bioavailability was about 33.01%. Moreover, YMR-65 was
      extensively distributed in heart, liver, spleen, lung, kidney, stomach, intestine
      and testis and the highest were detected in heart, followed by stomach, intestine
      and liver. The majority of YMR-65 was excreted via feces and its accumulative
      excretion ratio during the period of 96 h was 19.83 +/- 3.01%, but only 1.54 +/-
      0.37 and 0.215 +/- 0.026% for urine within 96 h and bile within 10 h after
      intravenous administration, respectively, though the fecal and urine excretion
      were incomplete within 96 h. 3. In summary, this study defined the
      pharmacokinetic characteristics of YMR-65 in vivo and the important data can be a
      useful resource for further research and development.

PMID- 29050521
TI  - Glutamate receptor antagonists with the potential for migraine treatment.
AB  - INTRODUCTION: Preclinical, clinical, and other (e.g., genetic) evidence support
      the concept that migraine susceptibility may at least partially result from a
      glutamatergic system disorder. Therefore, the receptors of the glutamatergic
      system are considered relatively new targets for investigational drugs to treat
      migraine. Investigational and established glutamate receptor antagonists (GluRAs)
      have been shown to possess antinociceptive properties in preclinical models of
      trigeminovascular nociception and have been evaluated in clinical trials. This
      review focuses on preclinical and clinical studies of GluRAs for the treatment of
      migraine. Areas covered: A PubMed database search (from 1987 to December 2016)
      and a review of published studies on GluRAs in migraine were conducted. Expert
      opinion: All published clinical trials of investigational GluRAs have been
      unsuccessful in establishing benefit for acute migraine treatment. Clinical trial
      results contrast with the preclinical data, suggesting that glutamate (Glu) does
      not play a decisive role after the attack has already been triggered. These
      antagonists may instead be useful for migraine prophylaxis. Improving patient
      care requires further investigating and critically analyzing the role of Glu in
      migraine, designing experimental models to study more receptors and their
      corresponding antagonists, and identifying biomarkers to facilitate trials
      designed to target specific subgroups of migraine patients.

PMID- 29050523
TI  - Microbiota, a forgotten relic of vaccination.

PMID- 29050522
TI  - Metabolism of megestrol acetate in vitro and the role of oxidative metabolites.
AB  - 1. There is limited knowledge regarding the metabolism of megestrol acetate (MA),
      as it was approved by FDA in 1971, prior to the availability of modern tools for
      identifying specific drug-metabolizing enzymes. We determined the cytochrome
      P450s (P450s) and UDP-glucuronosyltransferases (UGTs) that metabolize MA,
      identified oxidative metabolites and determined pharmacologic activity at the
      progesterone, androgen and glucocorticoid receptors (PR, AR and GR,
      respectively). 2. Oxidative metabolites were produced using human liver
      microsomes (HLMs), and isolated for mass spectral (MS) and nuclear magnetic
      resonance (NMR) analyses. We screened recombinant P450s using MA at 62 MUM (HLM
      Km for metabolite 1; M1) and 28 MUM (HLM Km for metabolite 2; M2). UGT isoforms
      were simultaneously incubated with UDPGA, nicotinamide adenine dinucleotide
      phosphate (NADPH), CYP3A4 and MA. Metabolites were evaluated for pharmacologic
      activity on the PR, AR and GR. CYP3A4 and CYP3A5 are responsible for oxidative
      metabolism of 62 MUM MA. 3. At 28 MUM substrate concentration, CYP3A4 was the
      only contributing enzyme. Mass spectral and NMR data suggest metabolism of MA to
      two alcohols. After oxidation, MA is converted into two secondary glucuronides by
      UGT2B17 among other UGTs. MA, M1 and M2 had significant pharmacologic activity on
      the PR while only MA showed activity on the AR and GR.

PMID- 29050524
TI  - Transcranial Doppler Systolic Flow Index and ICP-Derived Cerebrovascular
      Reactivity Indices in Traumatic Brain Injury.
AB  - The purpose of our study was to explore relationships between transcranial
      Doppler (TCD) indices of cerebrovascular reactivity and those derived from
      intracranial pressure (ICP). Goals included: A) confirming previously described
      co-variance patterns of TCD/ICP indices, and B) describing thresholds for
      systolic flow index (Sx; correlation between systolic flow velocity [FVs] and
      cerebral perfusion pressure [CPP]) associated with outcome. In a retrospective
      cohort of traumatic brain injury (TBI) patients: with TCD and ICP monitoring, we
      calculated various continuous indices of cerebrovascular reactivity: A) ICP
      (pressure reactivity index [PRx]: correlation between ICP and mean arterial
      pressure [MAP]; PAx: correlation between pulse amplitude of ICP [AMP] and MAP;
      RAC: correlation between AMP and CPP) and B) TCD (mean flow index [Mx]:
      correlation between mean flow velocity [FVm] and CPP; Mx_a: correlation between
      FVm and MAP; Sx: correlation between FVs and CPP; Sx_a: correlation between FVs
      and MAP; Dx: correlation between diastolic flow velocity [FVd] and CPP; Dx_a:
      correlation between FVd and MAP). We assessed the relationships via various
      statistical techniques, including: principal component analysis, agglomerative
      hierarchal clustering, and k-means cluster analysis (KMCA). We performed
      sequential chi2 testing to define thresholds associated with outcome for Sx/Sx_a.
      Outcome was assessed at 6 months via dichotomized Glasgow Outcome Score (GOS): A)
      Favorable (GOS 4 or 5) versus Unfavorable (GOS 3 or less), B) Alive versus Dead.
      We analyzed 410 recordings in 347 patients. All analyses confirmed our previously
      described co-variance of Sx/Sx_a with ICP-derived indices. Sx displayed
      thresholds of -0.15 for unfavorable outcome (p < 0.0001) and -0.20 for mortality
      (p < 0.0001). Sx_a displayed thresholds of +0.05 (p = 0.019) and -0.10 (p =
      0.0001) for alive/dead and favorable/unfavorable outcomes. TCD systolic indices
      are most closely associated with ICP indices. Sx and Sx_a likely provide better
      approximation of ICP indices, compared with Mx/Mx_a/Dx/Dx_a. Sx provides superior
      outcome prediction, versus Mx, with defined thresholds.

PMID- 29050525
TI  - Evaluation of nano-ZnOs as a novel Zn source for marine fish: importance of
      digestive physiology.
AB  - Waterborne nanotoxicology of zinc oxide nanoparticles (nano-ZnOs) has been
      extensively studied over the past decade, whereas their potential dietary
      toxicity and applications were seldom investigated. In the present study, we
      systematically investigated both short-term bioavailability and chronic effects
      of nano-ZnOs to two marine fish (marine medaka Oryzias melastigma and red drum
      Sciaenops ocellatus). At normal supplementary level (80 mg Zn/kg), red drum (with
      a stomach) had similar assimilation efficiencies of nano-ZnOs and ZnCl2.
      Correspondingly, in vitro digestion experiments showed the continuous dissolution
      of nano-ZnOs in acid environment. In contrast, nano-ZnOs were more bioavailable
      than ZnCl2 to medaka (stomach-less) at 80 mg Zn/kg supplementary level. There
      results were further validated by using bulk-ZnOs. Chronic dietary exposure to
      nano-ZnOs (80 mg/kg) significantly enhanced the antioxidative defenses in medaka,
      with no negative effect on fish growth. Beneficial effects disappeared in the
      high dietary nano-ZnOs (300 mg/kg) treatment. For the first time, we provided
      direct evidence that nano-ZnOs was more bioavailable than ZnCl2 and bulk-ZnOs to
      stomach-less fish at normal dietary Zn inclusion level (<80 mg/kg), with
      potential benefits on antioxidative defenses. It is also necessary to pay
      attention to the dietary nano-ZnOs toxicity on stomach-less fish due to the
      presence of real 'nano-effects.'

PMID- 29050526
TI  - Long-Term Quality of Life After Extracorporeal Membrane Oxygenation in ARDS
      Survivors: Systematic Review and Meta-Analysis.
AB  - PURPOSE: Extracorporeal membrane oxygenation (ECMO) is an increasingly prevalent
      treatment for acute respiratory failure (ARF). To evaluate the impact of ECMO
      support on long-term outcomes for critically ill adults with ARF. METHODS: We
      searched electronic databases 1948 through to November 30 2016; selected
      controlled trials or observational studies of critically ill adults with acute
      respiratory distress syndrome, examining long-term morbidity specifically health
      related quality of life (HRQL); 2 authors independently selected studies,
      extracted data, and assessed methodological quality. ANALYSIS: Of the 633
      citations, 1 randomized controlled trial and 5 observational studies met the
      selection criteria. Overall quality of observational studies was moderate to high
      (mean score on Newcastle-Ottawa scale, 7.2/9; range, 6-8). In 3 studies (n =
      245), greater decrements in HRQL were seen for survivors of ECMO when compared to
      survivors of conventional mechanical ventilation (CMV) as measured by the Short
      Form 36 (SF-36) scores ([ECMO-CMV]: 5.40 [95% confidence interval, CI, 4.11 to
      6.68]). As compared to CMV survivors, those who received ECMO experienced
      significantly less psychological morbidity (2 studies; n = 217 [ECMO-CMV]: mean
      weighted difference [MWD], -1.31 [95% CI, -1.98 to -0.64] for depression and MWD,
      -1.60 [95% CI, -1.80 to -1.39] for anxiety). CONCLUSIONS: Further studies are
      required to confirm findings and determine prognostic factors associated with
      more favorable outcomes in survivors of ECMO.

PMID- 29050527
TI  - How might transbronchial cryobiopsy improve diagnosis and treatment of diffuse
      parenchymal lung disease patients?

PMID- 29050528
TI  - UV-Assisted 3D Bioprinting of Nanoreinforced Hybrid Cardiac Patch for Myocardial
      Tissue Engineering.
AB  - Biofabrication of cell supportive cardiac patches that can be directly implanted
      on myocardial infarct is a potential solution for myocardial infarction repair.
      Ideally, cardiac patches should be able to mimic myocardium extracellular matrix
      for rapid integration with the host tissue, raising the need to develop cardiac
      constructs with complex features. In particular, cardiac patches should be
      electrically conductive, mechanically robust and elastic, biologically active and
      prevascularized. In this study, we aim to biofabricate a nanoreinforced hybrid
      cardiac patch laden with human coronary artery endothelial cells (HCAECs) with
      improved electrical, mechanical, and biological behavior. A safe ultraviolet (UV)
      exposure time with insignificant effect on cell viability was identified for
      methacrylated collagen (MeCol) micropatterning. The effects of carboxyl
      functionalized carbon nanotubes (CNTs) on MeCol and alginate matrix morphology,
      mechanical properties, electrical behavior, and cellular response were
      investigated at different CNT mass ratios. A UV-integrated 3D-bioprinting
      technique was implemented to create hybrid hydrogel constructs consisting of CNT
      incorporated alginate framework and cell-laden MeCol. The compressive modulus,
      impedance, and swelling degree of hybrid constructs were assessed over 20 days of
      incubation in culture medium at 37 degrees C for different CNT mass ratios. The
      HCAEC viability, proliferation, and differentiation in the context of the
      bioprinted hybrid constructs were assessed over 10 days in vitro. The
      functionalized CNTs provided a highly interconnected nanofibrous meshwork that
      significantly improved viscoelastic behavior and electrical conductivity of photo
      cross-linked MeCol. Alginate-coated CNTs provided a nanofilamentous network with
      fiber size of ~25-500 nm, improving not only electrical and mechanical properties
      but also HCAEC attachment and elongation compared to pristine alginate. The CNT
      reinforced 3D-printed hybrid constructs presented significantly higher stiffness
      and electrical conductivity particularly in the physiologically relevant
      frequency range (~5 Hz). The CNT-reinforced hybrid implants maintained a
      significantly higher swelling degree over 20 days of culturing compared to CNT
      free hybrid constructs. For a selected CNT mass ratio, HCAECs presented
      significant cellular proliferation, migration, and differentiation (lumen-like
      formation) over 10 days of incubation in vitro. Findings from this study deliver
      essential steps toward developing conductive, robust, and potentially
      prevascularized hybrid cardiac patches.

PMID- 29050529
TI  - E-learning in medical education: the potential environmental impact.
AB  - Introduction There is a growing interest in the use of e-learning in medical
      education. However until recently there has been little interest in the potential
      environmental benefits of e-learning. This paper models various environmental
      outcomes that might emerge from the use of an e-learning resource (BMJ Learning)
      in CPD. Methods We modeled the use of e-learning as a component of CPD and
      evaluated the potential impact of this use on the learner's carbon footprint. We
      looked at a number of models - all from the perspective of a General Practitioner
      (GP). We assumed that all GPs completed 50 h or credits of CPD per year. Results
      High users of e-learning can reduce their carbon footprint - mainly by reducing
      their travel to face-to-face events (reducing printing also has a small
      beneficial effect). A high user of e-learning can reduce the carbon footprint
      that relates to their CPD by 18.5 kg. Discussion As global warming continues to
      pose a risk to human and environmental health, we feel that doctors have a duty
      to consider learning activities (such as e-learning) that are associated with a
      lower carbon footprint.

PMID- 29050530
TI  - Hospital clinical supervisors' completion of Workplace-based Assessments (WPBAs)
      across specialties.

PMID- 29050531
TI  - Anti-NMDA receptor encephalitis: still unknown and underdiagnosed by physicians
      and especially by psychiatrists?
AB  - Anti-NMDA receptor encephalitis is an autoimmune disorder confirmed by the
      presence of antibodies against the NMDA-receptor in serum or CSF. This case
      report describes a young woman with anti-NMDA receptor encephalitis, who
      presented with prominent psychiatric symptoms. There was a crucial delay in
      diagnosis and necessary treatment due to the fact that the clinical presentation
      was diagnosed and treated as a first psychotic episode. Physicians and especially
      psychiatrists, should consider the possibility of an autoimmune encephalitis in
      their differential diagnosis in every new onset psychotic episode with rapid
      progression, the presence of pathognomonic orofacial dyskinesia, the lack of
      psychiatric history, and the non-responding to psychopharmacological treatment.
      Early diagnosis and treatment is essential for recovery and may improve the
      prognosis.

PMID- 29050532
TI  - Genotoxic evaluation of newly synthesized iminothiazolidinones.
AB  - The current study was designed to assess the potential toxicological effects of
      newly synthesized iminothiazolidinones by employing Ames Salmonella, Escherichia
      coli WP2, Zea mays seed germination, and random amplified polymorphic DNA (RAPD)
      assay systems. The bacterial tester strains S. typhimurium TA1535, TA1537,
      TA1538, TA98, TA100, and E. coli WP2 uvrA were chosen to test the direct gene
      mutation inducing capabilities of the test materials in prokaryotic systems and
      Z. mays seeds for determination of potential toxicological effects in eukaryotic
      systems. OPA-3 and OPA-6 primers were used in the RAPD analysis to determine
      genotoxic activities on the eukaryotic genomes. According to the results, none of
      the test materials showed significant mutagenic activity on the bacterial tester
      strains at the chosen concentrations. Additionally, none of the tested compounds
      showed inhibition of the germination of Z. mays seeds. In contrast, the RAPD
      analysis results were inconsistent with the bacterial reversion assays and the
      seed germination assay results. All test materials significantly changed the RAPD
      profiles for OPA-3; however, only compound 5 showed a significant change for OPA
      6 when compared with the control groups. In conclusion, the newly synthesized
      iminothiazolidinone derivatives (C1-C5) were determined as potentially genotoxic
      compounds and they should be checked with multiple toxicology test systems before
      further studies to determine their actual use.

PMID- 29050533
TI  - Insights into the pollutant-removal performance and DOM characteristics of
      stormwater runoff during grassy-swales treatment.
AB  - The water purification performance of grassy swales for treating stormwater road
      runoff was evaluated using a simulated experimental device in two different
      seasons. The results showed that the removal rates for total suspended solids
      (TSS), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus
      (TP) reached 89.90%, 56.71%, 32.37%, and 19.67%, respectively, in summer, and
      34.09%, 7.75%, 56.71%, and 13.33%, respectively, in winter, suggesting that
      grassy swales showed higher water purification performance in summer than in
      winter. Soil filtration in grassy swales also showed high removal rates of TSS,
      COD, TN and TP in summer (98.13%, 59.10%, 33.82%, and 24.59% respectively). The
      structure, composition and source of dissolved organic matter (DOM) were
      investigated using ultraviolet visible (UV-Vis) spectra and fluorescence spectra.
      The spectral parameters indicated a relatively high humification and aromaticity
      of DOM, and a relatively higher contribution of organic matter derived from
      microbial substances in summer than in winter. In addition, grassy-swale
      treatment showed a slight decrease in metal-ion concentrations at the surface,
      while the removal rates in the bottom samples were 38.42%, 40.59%, 33.81%, and
      40.06% for Cu2+, Cd2+, Pb2+, and Zn2+, respectively. The results of 2D-COS
      suggested that grass swales treatment can change the binding sites and binding
      sequencing of DOM with heavy metals and further influence the metal speciation,
      mobility and biotoxicity.

PMID- 29050535
TI  - Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus
      erythematosus.
AB  - Objectives The aim of this study was to investigate the association between
      antiphospholipid antibodies and non-thrombotic and non-gestational manifestations
      of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients
      with persistently positive antiphospholipid antibodies or lupus anticoagulant
      were identified and grouped as systemic lupus erythematosus with antiphospholipid
      syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid
      antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and
      systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were
      compared in terms of non-thrombotic systemic lupus erythematosus manifestations
      and laboratory features retrospectively. Results A total of 150 systemic lupus
      erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL,
      were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia
      were more common in antiphospholipid antibody positive systemic lupus
      erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the
      SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and
      titers of specific antiphospholipid antibodies did not differ between the SLE-APS
      and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or
      persistent antiphospholipid antibodies may be related to non-thrombotic and non
      gestational systemic lupus erythematosus manifestations. Patients with systemic
      lupus erythematosus plus antiphospholipid syndrome and persistent
      antiphospholipid antibodies without antiphospholipid syndrome also differ in
      terms of systemic lupus erythematosus manifestations.

PMID- 29050534
TI  - Low copy numbers of complement C4 and homozygous deficiency of C4A may predispose
      to severe disease and earlier disease onset in patients with systemic lupus
      erythematosus.
AB  - Objectives Low copy numbers and deletion of complement C4 genes are potent risk
      factors for systemic lupus erythematosus (SLE). However, it is not known whether
      this genetic association affects the clinical outcome. We investigated C4 copy
      number variation and its relationship to clinical and serological features in a
      Northern European lupus cohort. Methods We genotyped the C4 gene locus using
      polymerase chain reaction (PCR)-based TaqMan assays in 169 patients with SLE
      classified according to the 1997 revised American College of Rheumatology (ACR)
      criteria and in 520 matched controls. In the patient group the mean C4 serum
      protein concentrations nephelometrically measured during a 12-month period prior
      to genetic analysis were compared to C4 gene copy numbers. Severity of disease
      was classified according to the intensity of the immunosuppressive regimens
      applied and compared to C4 gene copy numbers, too. In addition, we performed a
      TaqMan based analysis of three lupus-associated single-nucleotide polymorphisms
      (SNPs) located inside the major histocompatibility complex (MHC) to investigate
      the independence of complement C4 in association with SLE. Results Homozygous
      deficiency of the C4A isotype was identified as the strongest risk factor for SLE
      (odds ratio (OR) = 5.329; p = 7.7 * 10-3) in the case-control comparison.
      Moreover, two copies of total C4 were associated with SLE (OR = 3.699; p = 6.8 *
      10-3). C4 serum levels were strongly related to C4 gene copy numbers in patients,
      the mean concentration ranging from 0.110 g/l (two copies) to 0.256 g/l (five to
      six copies; p = 4.9 * 10-6). Two copies of total C4 and homozygous deletion of
      C4A were associated with a disease course requiring cyclophosphamide therapy (OR
      = 4.044; p = 0.040 and OR = 5.798; p = 0.034, respectively). Homozygous deletion
      of C4A was associated with earlier onset of SLE (median 24 vs. 34 years; p =
      0.019) but not significant after correction for multiple testing. SNP analysis
      revealed a significant association of HLA-DRB1*0301 with SLE (OR = 2.231; p =
      1.33 * 10-5). Conclusions Our findings confirm the important role of complement
      C4 genes in the development of SLE. Beyond the impact on the susceptibility for
      lupus, C4 copy numbers may be related to earlier onset and a more severe course
      of the disease. The association of homozygous deletion of C4A and SLE is
      accompanied by the presence of HLA-DRB1*0301 without a proven pathophysiological
      mechanism.

PMID- 29050537
TI  - Hospitalizations among Danish SLE patients: a prospective study on incidence,
      causes of admission and risk factors in a population-based cohort.
AB  - Objective To determine the incidence, duration and cause of hospitalization in a
      cohort of Danish patients with systemic lupus erythematosus (SLE). In addition,
      we investigated risk factors for admission and prolonged hospital stay. Methods A
      total of 155 SLE patients from a population-based cohort were included in the
      study during a period of 70 months, from January 2007 to October 2012. Data on
      frequency, cause and duration of hospitalizations were obtained by review of
      medical charts. Data on disease manifestations, organ damage and treatment were
      collected prospectively. Results A total of 101 of the 155 SLE patients (65%) had
      one or more hospitalization during the study period. The incidence rate of all
      hospitalizations was 0.50 per year. Leading causes of admission were
      complications to SLE or its treatment, but infections were also common. Mean
      duration of hospital stay was 6.4 +/- 10.5 days, and SLE Disease Activity Index
      2000 (SLEDAI-2K) on admission emerged as a risk factor for prolonged hospital
      stay. Conclusion Danish SLE patients experience frequent admissions to hospital.
      Complications to SLE or its treatment, as well as infections, are leading causes
      of admission. High SLEDAI-2K on admission is a risk factor for prolonged hospital
      stay.

PMID- 29050536
TI  - The correlation of urinary podocytes and podocalyxin with histological features
      of lupus nephritis.
AB  - Objectives The objective of this study was to test the correlation of urinary
      podocyte number (U-Pod) and urinary podocalyxin levels (U-PCX) with histology of
      lupus nephritis. Methods This was an observational, cross-sectional study. Sixty
      four patients were enrolled: 40 with lupus nephritis and 24 without lupus
      nephritis (12 lupus nephritis patients in complete remission and 12 systemic
      lupus erythematosus patients without lupus nephritis). Urine samples were
      collected before initiating treatment. U-Pod was determined by counting
      podocalyxin-positive cells, and U-PCX was measured by sandwich ELISA, normalized
      to urinary creatinine levels (U-Pod/Cr, U-PCX/Cr). Results Lupus nephritis
      patients showed significantly higher U-Pod/Cr and U-PCX/Cr compared with patients
      without lupus nephritis. U-Pod/Cr was high in proliferative lupus nephritis
      (class III+/-V/IV+/-V), especially in pure class IV (4.57 (2.02-16.75)), but low
      in pure class V (0.30 (0.00-0.71)). U-Pod/Cr showed a positive correlation with
      activity index ( r=0.50, P=0.0012) and was independently associated with cellular
      crescent formation. In contrast, U-PCX/Cr was high in both proliferative and
      membranous lupus nephritis. Receiver operating characteristic analysis revealed
      significant correlation of U-Pod/Cr with pure class IV, class IV+/-V and cellular
      crescent formation, and the combined values of U-Pod/Cr and U-PCX/Cr were shown
      to be associated with pure class V. Conclusions U-Pod/Cr and U-PCX/Cr correlate
      with histological features of lupus nephritis.

PMID- 29050538
TI  - Evaluation of the head and neck cancer patient population and the incidence of
      hospitalization at an academic medical center.
AB  - Purpose Patients with head and neck cancer are at risk for disease- and treatment
      related toxicities that may be severe enough to require hospitalization. The risk
      factors associated with hospitalization in these patients are not well defined.
      Methods We conducted a single-center, retrospective observational study of
      patients with head and neck cancer receiving chemotherapy at an academic medical
      center infusion clinic in a one-year period. The primary objective was to
      characterize the head and neck cancer population at an academic medical center.
      Secondary objectives included describing the clinical and social factors
      associated with hospitalization. Results There were 109 patients with head and
      neck cancer included in the analysis. Of these patients, 38 (35%) were
      hospitalized. The factors that were significantly associated with hospitalization
      on univariable logistic regression were former alcohol abuse, being on a
      nonstandard of care chemotherapy regimen, and having a chemotherapy agent
      discontinued. On multivariable logistic regression, the factor that was
      significantly associated with hospitalization was having a chemotherapy agent
      discontinued. The most common reasons for hospitalization included shortness of
      breath/respiratory failure, fever/neutropenic fever, and infection. The most
      common new supportive care medications prescribed at discharge were stool
      softeners or laxatives and opioids. Conclusion This study identified several
      factors which may be useful to identify patients as high risk for hospitalization
      and the next steps will be to determine and study the role of the pharmacist in
      preventing hospitalization of these patients. Further studies are needed to
      assess the impact of adding a pharmacist to the head and neck cancer
      multidisciplinary team.

PMID- 29050539
TI  - Sustaining care for a parent with dementia: an indefinite and intertwined
      process.
AB  - This study aimed to understand how adult children sustain caring for persons with
      dementia (PwDs) within their family and formal care contexts in Canada. Half-day
      focus groups were conducted with adult daughters and adult sons in Toronto,
      Canada. Using constructivist grounded theory, we examined both substantive
      concepts and group dynamics. Sustaining care was interpreted as an indefinite
      process with three intertwined themes: reproducing care demands and dependency,
      enacting and affirming values, and "flying blind" in how and how long to sustain
      caring (i.e., responding to immediate needs with limited foresight). Family
      values and relationships, mistrust toward the institutional and home care
      systems, and obscured care foresight influenced care decisions and challenged
      participants in balancing their parents' needs with their own. Positive and
      negative aspects of care were found to influence one another. The implications of
      these findings for research and policy are discussed.

PMID- 29050540
TI  - Somatosensory stimulation to improve hand and upper limb function after stroke-a
      systematic review with meta-analyses.
AB  - Background Somatosensory stimulation may have a positive impact on recovery of
      motor function by maintaining cortical representation of the hand and acting to
      prime the motor system for movement. Objective Determine the efficacy of
      somatosensory stimulation on upper limb motor function after stroke. Methods Five
      electronic databases (MEDLINE, CINAHL, Embase, PEDro and OT Seeker) were searched
      from inception to October 2016. Included studies were English-language randomized
      controlled trials where a sensory intervention was applied below the elbow to
      improve upper limb motor control of adults after stroke. One outcome needed to
      measure arm function at an impairment or activity level. Study selection and
      quality assessment (using the PEDro scale) were independently conducted by two
      reviewers. Meta-analysis was completed where there was sufficient homogeneity
      between trials. Results Fifteen articles were included reporting data from 14
      randomized controlled trials (627 participants). There was low-quality evidence
      from four trials that sensory electrical stimulation did not improve upper limb
      activity compared to placebo (SMD 0.4, 95%CI -0.07 to 0.87, I2 38%) and moderate
      quality evidence from three trials that it did not improve motor impairment (MD
      3.45 units, 95%CI -1.47 to 8.36, I2 35%). Low-quality evidence from two trials
      demonstrated that therapist-delivered sensory stimulation did not improve upper
      limb activity (SMD 0.25, 95%CI -0.20 to 0.69, I2 0%) compared to usual care.
      Conclusion Current low- to moderate-quality evidence suggests somatosensory
      stimulation is not effective in improving upper limb motor impairment or activity
      after stroke.

PMID- 29050541
TI  - The development and evaluation of peer-facilitated dementia workshops in general
      practice.
AB  - BACKGROUND: Rising dementia prevalence rates, combined with the policy objectives
      of integrated care in the community, means that general practitioners (GPs) are
      playing an increasing and pivotal role in dementia care. However, GPs are
      challenged by dementia care and have identified it as an area of learning need.
      We describe the development, roll-out and evaluation of peer-facilitated
      workshops for GPs, as part of a national programme to support GPs in their
      delivery of dementia care. METHOD: Informed by a triangulated educational needs
      analysis, small-group case-based workshops were designed. Five GPs were trained
      as facilitators and delivered workshops in GP practices within their own
      locality. A mixed-methods evaluation was undertaken, incorporating participant
      completion of post-workshop questionnaires along with the collection and analysis
      of qualitative data obtained from a focus group with workshop facilitators.
      RESULTS: 104 GPs attended 39 workshops (median attendance number 3, range 2-9).
      The majority of participants reported an improvement in their knowledge and
      confidence in dementia care. In particular, participants felt that workshop
      content was relevant and they liked peer-facilitation within their own practices.
      Facilitators emphasised the importance of skilful facilitation of sensitive
      topics and described the tension between being regarded as a facilitator and a
      subject expert. CONCLUSIONS: The findings of this study indicate that practice
      based, peer-facilitated, small-group workshops improve self-reported knowledge
      and confidence in dementia care and are well-received by GPs. Findings further
      suggest that similar educational approaches may be effective in supporting GPs in
      other areas of complex chronic care in general practice.

PMID- 29050542
TI  - Hepatic Mastocytosis in Japanese Black Cattle.
AB  - In 5 Japanese Black steers (2-2.4 years old) that originated from 5 different
      feedlots, the livers were found at slaughter to have multiple nodular or cordlike
      lesions (5 steers) and an extensive fibrotic area (1 steer). Microscopic changes
      included extensive fibroplasia in the portal tracts and chronic proliferative
      endophlebitis-like lesions confined to the portal vein branches. Fibroplasia was
      much more prominent in the macroscopic fibrotic lesion of 1 steer. Portal vein
      branches presented irregular variciform dilation of the vascular lumen and
      fibroplastic changes in the subendothelial areas that showed occasional
      hemorrhage and were simultaneously infiltrated with large numbers of mast cells
      and moderate to large numbers of eosinophils. Within these subendothelial
      regions, not only did mast cells exhibit cytologically atypical features, but
      they also formed multifocal nodules. The venous lesions may represent a variant
      of mastocytosis with specific involvement of the hepatic portal vein branches in
      cattle.

PMID- 29050543
TI  - Granulomatous Necrotizing Myositis in Swine Affected by Porcine Circovirus
      Disease.
AB  - Porcine circovirus type 2 (PCV2) is associated with multiple clinical syndromes
      in pigs, known as porcine circovirus diseases. This work describes an outbreak of
      porcine circovirus diseases with severe lesions affecting the skeletal muscle.
      Ninety-two pigs had apathy, weight loss, and diarrhea over a clinical course of 7
      to 10 days. Approximately 30 of the pigs had stiff gait, muscle weakness, hind
      limb paresis, and recumbency. Twelve of the 92 pigs were necropsied, and 4 had
      pale discoloration of skeletal muscles with microscopic lesions of granulomatous
      necrotizing myositis. Immunohistochemistry of skeletal muscle showed that PCV2
      antigen was located primarily in the cytoplasm and nuclei of macrophages,
      lymphocytes, and multinucleated giant cells, with a lower amount in the cytoplasm
      of endothelial cells, necrotic fibers, and satellite cells. Affected muscle
      samples were polymerase chain reaction-positive for PCV2 and the amplicon
      exhibited 99% identity with sequences belonging to the PCV2b genotype. Locomotor
      clinical signs and granulomatous necrotizing myositis should be considered as
      another expression of PCV2 infection in pigs.

PMID- 29050547
TI  - Editorial: Development of Anticancer Reagents.

PMID- 29050544
TI  - Editorial: Nanotechnology and Biomaterials for Cell and Drug Therapy.

PMID- 29050548
TI  - Does intranasal steroid spray technique affect side effects and compliance?
      Results of a patient survey.
AB  - BACKGROUND: Intranasal steroid sprays are fundamental in the medical management
      of inflammatory rhinological conditions. Side effects are common, but these may
      be related to the method of application rather than the medication itself.
      METHODS: A survey was distributed to patients using intranasal steroid sprays at
      the ENT out-patient clinic at Aberdeen Royal Infirmary over three months. This
      evaluated the spray technique used, side effects and compliance. RESULTS: Of 103
      patients, 22 patients (21.4 per cent) reported side effects, including nasal
      irritation and epistaxis. Of the 20 patients with epistaxis, 80 per cent used an
      ipsilateral hand technique (p = 0.01). Thirty patients demonstrated poor
      compliance because of lack of symptom improvement or side effects. Seventy-seven
      per cent of this group used the ipsilateral hand technique. CONCLUSION: Patients
      who used their ipsilateral hand to apply the intranasal steroid spray were more
      likely to develop epistaxis and have poor compliance than those who used other
      techniques. Patients who struggle with compliance because of side effects should
      avoid this method of intranasal steroid application.

PMID- 29050549
TI  - Biosorptive Removal of Cadmium by Tinospora cordifolia (Wild Giloy).
AB  - This research reports the efficacy of Tinospora cordifolia as a biosorbent for
      removing cadmium ions from industrial effluents. The biosorption capacity was
      found to be 38.91 mg Cd/g and 43.06 mg Cd/g, in batch and column mode
      experiments, respectively. The work included uptake capacity, an equilibrium
      study, and a column study at varying pH (1-9), contact time (5-240 min),
      biosorbent dosages (1-8 g), and initial metal concentration (10-1000 mg/L). Both
      Langmuir and Freundlich isotherm models were applied to study the dose-response
      behavior, and it was observed that the Freundlich model provided the highest R2
      value. Fourier transform infrared spectroscopy (FTIR) analysis indicated the
      involvement of hydroxyl, alkane, anhydride, halide, and amine functional groups.
      Multilayer adsorption as indicated by the Freundlich adsorption model, and
      multifunctional group interaction as identified in the FTIR analysis, explains
      the high adsorptive capacity. The biomass was successfully applied for the
      removal of cadmium from industrial effluents. Biosorbent also gave a higher
      removal percentage at a low pH value (pH 2). The feasibility and viability of the
      biomass for technocommercial utilization in effluent treatment appears high.

PMID- 29050550
TI  - Potential Changes in Chemical Soil Quality Resulting from Graywater Recycling for
      Landscape Irrigation.
AB  - The effects of graywater irrigation on soil chemical properties, and the
      accumulation of surfactants and antimicrobials, were investigated at three
      households in Arizona, California, and Colorado over the duration of two to three
      years. No negative effects were observed, with respect to sodium and boron
      accumulation in soil, over the duration of this study. Graywater irrigation
      significantly increased organic matter and total inorganic nitrogen of the
      receiving soil (P < 0.05). Graywater loading rates and fertilizer application
      should be monitored to ensure that excessive amounts of nitrogen and phosphorus
      are not applied to the soil. Notable concentrations of antimicrobials were
      detected in surface soil samples. It is suggested that the effect of
      antimicrobials on soil microbial health, and the potential for formation of
      antibiotic-resistant genes, be further investigated. Surfactant concentration in
      soil samples substantially increased after graywater application, compared with
      baseline samples, and then remained fairly constant over time.

PMID- 29050552
TI  - Sexual health and students: the pathways travelled by those with sexual health
      concerns.
AB  - The aim of this study was to identify the type of research (Internet, phone
      lines, friends, family, media or medical journal) undertaken by university
      students with sexual health concerns, and the effect this research had on their
      healthcare-seeking behaviour. The Internet was the most common (46%) first point
      of call for health information, closely followed by doctors (40%). Of those who
      undertook extra research, the majority subsequently went to a doctor. Health
      practitioners need to be aware of this tendency for independent research.

PMID- 29050554
TI  - Natural Variation and Genetics of Photoperiodism in Wyeomyia smithii.
AB  - Seasonal change in the temperate and polar regions of Earth determines how the
      world looks around us and, in fact, how we live our day-to-day lives. For
      biological organisms, seasonal change typically involves complex physiological
      and metabolic reorganization, the majority of which is regulated by
      photoperiodism. Photoperiodism is the ability of animals and plants to use day
      length or night length, resulting in life-historical transformations, including
      seasonal development, migration, reproduction, and dormancy. Seasonal timing
      determines not only survival and reproductive success but also the structure and
      organization of complex communities and, ultimately, the biomes of Earth. Herein,
      a small mosquito, Wyeomyia smithii, that lives only in the water-filled leaves of
      a carnivorous plant over a wide geographic range, is used to explore the genetic
      and evolutionary basis of photoperiodism. Photoperiodism in W. smithii is
      considered in the context of its historical biogeography in nature to examine the
      startling finding that recent rapid climate change can drive genetic change in
      plants and animals at break-neck speed, and to challenge the ponderous 80+ year
      search for connections between daily and seasonal time-keeping mechanisms.
      Finally, a model is proposed that reconciles the seemingly disparate 24-h daily
      clock driven by the invariant rotation of Earth about its axis with the
      evolutionarily flexible seasonal timer orchestrated by variable seasonality
      driven by the rotation of Earth about the Sun.

PMID- 29050555
TI  - Natural Variation in Human Clocks.
AB  - Our own species has a diurnal activity pattern and an average circadian period of
      24.2h. Exact determination of circadian period requires expensive and intrusive
      protocols, and investigators are therefore using chronotype questionnaires as a
      proxy quantitative measure. Both measures show a normal distribution suggestive
      of a polygenic trait. The genetic components of the 24-h feedback loop that
      generates circadian rhythms within our cells have been mapped in detail,
      identifying a number of candidate genes which have been investigated for genetic
      polymorphisms relating to the phenotypic variance. Key in this mechanism is the
      inhibitory complex containing period and cryptochrome proteins and interacting
      protein kinases and ubiquitin ligases, and the stability of this complex is
      recognized as the major determinant of circadian periodicity. The identification
      of the causative mutations in familial circadian rhythms sleep disorders has shed
      additional light into this mechanism. Mutations in the negative feedback protein
      encoding genes PER2 and CRY2 as well as the CSNK1D gene encoding casein kinase I
      delta have been shown to cause advanced sleep phase disorder, and a mutation in
      the CRY1 gene delayed sleep phase disorder. The candidate gene approach has also
      yielded a number of genetic associations with chronotype as determined by
      questionnaires. More recently, genome-wide association studies of chronotype have
      both confirmed associations with the candidate clock gene PER2 and identified a
      serious of novel genes associated with variability in circadian rhythmicity,
      which have yet to be explored. While considerable progress has thus been made
      with mapping the phenotypic diversity in human circadian rhythms and the genomic
      variability that causes it, studies to date have been mostly focused on
      individuals of European descent, and there is a strong need for research on other
      populations.

PMID- 29050556
TI  - Preface.

PMID- 29050553
TI  - Natural Variation of the Circadian Clock in Neurospora.
AB  - Most living organisms on earth experience daily and expected changes from the
      rotation of the earth. For an organism, the ability to predict and prepare for
      incoming stresses or resources is a very important skill for survival. This
      cellular process of measuring daily time of the day is collectively called the
      circadian clock. Because of its fundamental role in survival in nature, there is
      a great interest in studying the natural variation of the circadian clock.
      However, characterizing the genetic and molecular mechanisms underlying natural
      variation of circadian clocks remains a challenging task. In this chapter, we
      will summarize the progress in studying natural variation of the circadian clock
      in the successful eukaryotic model Neurospora, which led to discovering many
      design principles of the molecular mechanisms of the eukaryotic circadian clock.
      Despite the success of the system in revealing the molecular mechanisms of the
      circadian clock, Neurospora has not been utilized to extensively study natural
      variation. We will review the challenges that hindered the natural variation
      studies in Neurospora, and how they were overcome. We will also review the
      advantages of Neurospora for natural variation studies. Since Neurospora is the
      model fungal species for circadian study, it represents over 5 million species of
      fungi on earth. These fungi play important roles in ecosystems on earth, and as
      such Neurospora could serve as an important model for understanding the
      ecological role of natural variation in fungal circadian clocks.

PMID- 29050557
TI  - Agreement of the Resting Distal to Aortic Coronary Pressure With the
      Instantaneous Wave-Free Ratio.
AB  - BACKGROUND: Recently, 2 randomized controlled trials showed that the
      instantaneous wave-free ratio (iFR), a resting coronary physiological index, is
      noninferior to fractional flow reserve for guiding revascularization. The resting
      distal to aortic coronary pressure (Pd/Pa) measured at rest is another adenosine
      free index widely available in the cardiac catheterization laboratory; however,
      little is known about the agreement of Pd/Pa using iFR as a reference standard.
      OBJECTIVES: The goal of this study was to investigate the agreement of Pd/Pa with
      iFR. METHODS: A total of 763 patients were prospectively enrolled from 12
      institutions. iFR and Pd/Pa were measured under resting conditions. Using iFR
      <=0.89 as a reference standard, the agreement of Pd/Pa and its best cutoff value
      were assessed. RESULTS: According to the independent core laboratory analysis,
      iFR and Pd/Pa were analyzable in 627 and 733 patients (82.2% vs. 96.1%; p <
      0.001), respectively. The median iFR and Pd/Pa were 0.90 (interquartile range:
      0.85 to 0.94) and 0.92 (interquartile range: 0.88 to 0.95), and the 2 indices
      were highly correlated (R2 = 0.93; p < 0.001; iFR = 1.31 * Pd/Pa -0.31).
      According to the receiver-operating characteristic curve analysis, Pd/Pa showed
      excellent agreement (area under the curve: 0.98; 95% confidence interval: 0.97 to
      0.99; p < 0.001) with a best cutoff value of Pd/Pa <=0.91. The diagnostic
      accuracy, sensitivity, specificity, positive predictive value, and negative
      predictive value were 93.0%, 91.4%, 94.4%, 93.3%, and 92.7%, respectively. These
      results were similar in patients with acute coronary syndrome and stable angina.
      CONCLUSIONS: Pd/Pa was analyzable in a significantly higher number of patients
      than iFR. Pd/Pa showed excellent agreement with iFR, suggesting that it could be
      applied clinically in a similar fashion. (Can Contrast Injection Better
      Approximate FFR Compared to Pure Resting Physiology? [CONTRAST]; NCT02184117).

PMID- 29050559
TI  - Agreement and Differences Among Resting Coronary Physiological Indices: Are All
      Things Equal?

PMID- 29050558
TI  - Similarity and Difference of Resting Distal to Aortic Coronary Pressure and
      Instantaneous Wave-Free Ratio.
AB  - BACKGROUND: Instantaneous wave-free ratio (iFR) has been used in clinical
      practice to identify functionally significant stenosis and to guide treatment
      strategy. However, there are limited clinical data regarding another resting
      pressure-derived index, resting distal to aortic coronary pressure (Pd/Pa), and
      similarities and differences between resting Pd/Pa and iFR. OBJECTIVES: The
      authors investigated the changes in resting Pd/Pa and iFR according to anatomic
      and hemodynamic stenosis severity and their prognostic implications. METHODS:
      From the 3V FFR-FRIENDS (Clinical Implication of 3-vessel Fractional Flow
      Reserve) and the IRIS-FFR (Study of the Natural History of FFR Guided
      Percutaneous Coronary Intervention) studies, 1,024 vessels (n = 435) with
      available pre-intervention resting Pd/Pa and iFR were used to explore the changes
      in resting physiological indices according to percent diameter stenosis. Among
      115 patients who underwent 13N-ammonia positron emission tomography, the changes
      in those indices according to basal and hyperemic stenosis resistance and
      absolute hyperemic myocardial blood flow were compared. The association between
      physiological indices and the risk of 2-year major adverse cardiac events (MACE)
      (a composite of cardiac death, myocardial infarction, and ischemia-driven
      revascularization) were analyzed among 375 deferred patients. RESULTS: There was
      a significant linear correlation between resting Pd/Pa and iFR (R = 0.970; p <
      0.001, iFR = 1.370 * resting Pd/Pa - 0.370). Both resting Pd/Pa and iFR changed
      significantly according to percent diameter stenosis, basal and hyperemic
      stenosis resistance, and hyperemic absolute myocardial blood flow (all p values
      <0.001). Percent difference of iFR according to the increase in anatomic and
      hemodynamic severity was higher than that of resting Pd/Pa. Both resting Pd/Pa
      and iFR showed a significant association with the risk of 2-year MACE (resting
      Pd/Pa hazard ratio [per 0.10 increase]: 0.480; 95% confidence interval: 0.250 to
      0.923; p = 0.027; iFR hazard ratio [per 0.1 increase]: 0.586; 95% confidence
      interval: 0.373 to 0.919; p = 0.020) in deferred patients. However, the
      difference between the upper- and lower-bound estimated MACE rates according to
      the approximate measurement variability of each index was significantly higher
      with resting Pd/Pa compared with iFR (resting Pd/Pa 3.85 +/- 4.00% and iFR 3.27
      +/- 3.39%; p < 0.001). CONCLUSIONS: Both resting Pd/Pa and iFR showed similar
      associations with anatomic and hemodynamic stenosis severity and the risk of
      MACE. However, iFR was more sensitive to the difference in stenosis severity and
      showed a lower maximum difference in estimated MACE risk influenced by the
      measurement variability compared with resting Pd/Pa. (Clinical Implication of 3
      Vessel Fractional Flow Reserve [3V FFR-FRIENDS]; NCT01621438; and Study of the
      Natural History of FFR Guided Percutaneous Coronary Intervention [IRIS-FFR];
      NCT01366404).

PMID- 29050561
TI  - Cholesterol and Heart Failure: Is There an Important Connection?

PMID- 29050560
TI  - The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure: BIOSTAT-CHF
      Subanalysis.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low
      density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk
      predictor and a biotarget in atherosclerosis progression. OBJECTIVES: The aim of
      this study was to determine whether the PCSK9-LDLR axis could predict risk in
      patients with heart failure (HF). METHODS: The BIOSTAT-CHF (Biology Study to
      Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational,
      prospective, observational study that included patients with worsening HF signs
      and/or symptoms. The primary endpoints were all-cause mortality and the composite
      of mortality or unscheduled hospitalizations for HF. We implemented Cox
      proportional hazard regression to determine the simultaneously adjusted effect of
      PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT
      CHF risk scores. RESULTS: This study included 2,174 patients (mean age: 68 +/- 12
      years; 53.2% had a history of ischemic heart disease). Median (interquartile
      range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to
      3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%)
      composite endpoints were ascertained. A multivariable analysis, which included
      BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a
      positive linear association between PCSK9 levels and the risk of mortality
      (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020)
      and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar
      analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95%
      CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83
      to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance.
      CONCLUSIONS: The PCSK9-LDLR axis was associated with outcomes in patients with
      HF. Future studies must assess whether PCSK9 inhibition will result in better
      outcomes in HF.

PMID- 29050562
TI  - Renal Sympathetic Denervation Protects the Failing Heart Via Inhibition of
      Neprilysin Activity in the Kidney.
AB  - BACKGROUND: Sustained sympathetic activation contributes to the progression of
      myocardial cell injury, cardiac fibrosis, and left ventricular (LV) dysfunction
      in heart failure (HF). OBJECTIVES: This study investigated the effects of
      radiofrequency renal nerve denervation (RF-RDN) on the pathobiology of HF and the
      interaction between the renal sympathetic nerves and natriuretic peptide (NP)
      metabolism. METHODS: Spontaneously hypertensive rats (SHR) and normotensive
      Wistar-Kyoto rats (WKY) were subjected to 45 min of coronary artery ligation and
      reperfusion for 12 weeks. At 4 weeks post-reperfusion, SHR and WKY underwent
      either bilateral RF-RDN or sham-RDN. RESULTS: Following RF-RDN in both strains,
      LV ejection fraction remained significantly above those levels in respective sham
      RDN rats, and at the end of the 12-week study, rats in both strains had
      significantly reduced LV fibrosis and improved vascular function. RF-RDN therapy
      significantly improved vascular reactivity to endothelium-dependent and 
      independent vasodilators as well as vascular compliance in the setting of severe
      HF. Improvements in LV function were accompanied by significant elevations in
      circulating NP as compared to those associated with sham-RDN. Further
      investigation into the cause of increased circulating NP levels demonstrated that
      RF-RDN significantly inhibited renal neprilysin activity in SHR and WKY with HF.
      Likewise, chronic treatment with the beta1 antagonist bisoprolol inhibited renal
      neprilysin activity and increased circulation NP levels in WKY with HF.
      CONCLUSIONS: This study identifies a novel endogenous pathway by which the renal
      nerves participate in the degradation of cardioprotective NP. Furthermore,
      removal of the influence of the renal nerves on kidney function attenuates renal
      neprilysin activity, augments circulating NP levels, reduces myocardial fibrosis,
      and improves LV function in the setting of HF.

PMID- 29050563
TI  - Neprilysin and Heart Failure: A "Sympathetic" Relationship?

PMID- 29050565
TI  - The Com-PLEC-sity of Atrial Fibrillation Genetics.

PMID- 29050564
TI  - A Missense Variant in PLEC Increases Risk of Atrial Fibrillation.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have yielded variants at >30
      loci that associate with atrial fibrillation (AF), including rare coding
      mutations in the sarcomere genes MYH6 and MYL4. OBJECTIVES: The aim of this study
      was to search for novel AF associations and in doing so gain insights into the
      mechanisms whereby variants affect AF risk, using electrocardiogram (ECG)
      measurements. METHODS: The authors performed a GWAS of 14,255 AF cases and
      374,939 controls, using whole-genome sequence data from the Icelandic population,
      and tested novel signals in 2,002 non-Icelandic cases and 12,324 controls. They
      then tested the AF variants for effect on cardiac electrical function by using
      measurements in 289,297 ECGs from 62,974 individuals. RESULTS: The authors
      discovered 2 novel AF variants, the intergenic variant rs72700114, between the
      genes LINC01142 and METTL11B (risk allele frequency = 8.1%; odds ratio [OR]:
      1.26; p = 3.1 * 10-18), and the missense variant p.Gly4098Ser in PLEC (frequency
      = 1.2%; OR: 1.55; p = 8.0 * 10-10), encoding plectin, a cytoskeletal cross
      linking protein that contributes to integrity of cardiac tissue. The authors also
      confirmed 29 reported variants. p.Gly4098Ser in PLEC significantly affects
      various ECG measurements in the absence of AF. Other AF variants have diverse
      effects on the conduction system, ranging from none to extensive. CONCLUSIONS:
      The discovery of a missense variant in PLEC affecting AF combined with recent
      discoveries of variants in the sarcomere genes MYH6 and MYL4 points to an
      important role of myocardial structure in the pathogenesis of the disease. The
      diverse associations between AF variants and ECG measurements suggest
      fundamentally different categories of mechanisms contributing to the development
      of AF.

PMID- 29050566
TI  - How Low to Go With Glucose, Cholesterol, and Blood Pressure in Primary Prevention
      of CVD.
AB  - Diabetes, hyperlipidemia, and hypertension are modifiable risk factors that
      predict cardiovascular disease events. The effect of these risk factors on
      incident cardiovascular disease increases with progressively higher levels of
      glucose, low-density lipoprotein cholesterol, and blood pressure. The thresholds
      for initiating treatment of these modifiable risk factors and the optimal goals
      of risk factor modification are a focus of primary prevention research. Although
      an aggressive approach is appealing, adverse events may occur, and potential
      physiological barriers may exist. This paper discusses primary prevention of
      coronary heart disease that may be achieved through modification of diabetes,
      hyperlipidemia, and hypertension by summarizing current guidelines and pertinent
      clinical trial data from intervention trials that included a primary prevention
      cohort.

PMID- 29050567
TI  - Biological Phenotypes of Heart Failure With Preserved Ejection Fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) involves multiple
      pathophysiological mechanisms, which result in the heterogeneous phenotypes that
      are evident clinically, and which have potentially confounded previous HFpEF
      trials. A greater understanding of the in vivo human processes involved, and in
      particular, which are the causes and which are the downstream effects, may allow
      the syndrome of HFpEF to be distilled into distinct diagnoses based on the
      underlying biology. From this, specific interventions can follow, targeting
      individuals identified on the basis of their biological phenotype. This review
      describes the biological phenotypes of HFpEF and therapeutic interventions aimed
      at targeting these phenotypes.

PMID- 29050568
TI  - Cardiovascular Medicine Amid Evolving Health Policy: Time to Train a Generation
      of Policy Leaders.

PMID- 29050569
TI  - Arterial Dissection as a Cause of Intracranial Stenosis in East Asians.

PMID- 29050570
TI  - New Criteria for LVH Should Be Evaluated Against Age.

PMID- 29050571
TI  - Reply: New Criteria for LVH Should Be Evaluated Against Age.

PMID- 29050572
TI  - The Optimal Duration of Dual-Antiplatelet Therapy After Coronary Stenting:
      Shorter or Longer?

PMID- 29050573
TI  - Reply: The Optimal Duration of Dual-Antiplatelet Therapy After Coronary Stenting:
      Shorter or Longer?

PMID- 29050574
TI  - Superparamagnetic IPN gels of carrageenan/PHEMA excelling in shape retention.
AB  - Iron oxide nanoparticles-incorporated carrageenan (CAR)/PHEMA composites of
      interpenetrating network (IPN) type were successfully prepared by in situ ferrite
      synthesis in the polymer network. The IPN structure was constructed at CAR/PHEMA
      compositions of 15/85 and 40/60 (wt/wt) by polymerization and cross-linking of 2
      hydroxyethylmethacrylate as an impregnating solvent of CAR gels. As a result of
      this IPN construction, the composites were firm and showed a good shape
      retentivity in their gelatinous state. SQUID magnetometry and X-ray
      diffractometry were conducted for evaluation of the magnetic property of the
      inorganic-hybridized IPN composites. Magnetite particles with 10-30nm sizes were
      distributed inside the IPNs treated with the repeatable ferrite synthesis;
      thereby, the hybrids displayed a superparamagnetic character at ambient
      temperature. Specifically, the 40/60 CAR/PHEMA IPN imparted a practically
      passable value (10-15emu (g sample)-1) of saturation magnetization. The present
      IPN system offers a potential for application as a biocompatible magnetic
      material used in hydro-surroundings.

PMID- 29050575
TI  - One pot synthesis of gold nanoparticles using chitosan with varying degree of
      deacetylation and molecular weight.
AB  - Gold nanoparticles (AuNPs) were synthesized in one-step by reducing gold salt
      using nontoxic and biodegradable chitosan as dual roles of reducing agent and
      stabilizer. The obtained AuNPs were characterized with UV-vis spectroscopy and
      transmission electron microscopy. The results indicated that control over the
      size and shape of AuNPs is achieved through the careful selection of experimental
      conditions, such as reaction temperature, reaction time, concentration of gold
      salt and chitosan, and chitosan molecular parameters, i.e., degree of
      deacetylation (DD) and molecular weight (MW). At low chitosan concentration
      (0.005% and 0.01% (w/v)), individual spherical AuNPs with average particle size
      around 10nm were obtained regardless of chitosan DD and MW, while anisotropic
      AuNPs were obtained at concentration above 0.05% (w/v) for all investigated
      chitosan at the optimum condition (1mL of 1mmol/L HAuCl4 added to 3mL of chitosan
      solution reacted for 120min at 70 degrees C). The growth of larger polygonal
      AuNPs was promoted as the higher concentration and lower DD chitosan was used as
      reducing agent and stabilizer. Au nanoplate was synthesized by water-soluble
      chitosan (Mv 566kDa, DD 53%) at concentration above 0.15% (w/v). Chitooligomers
      (Mv 2.4kDa, DD 94%) showed the highest reduction ability for Au3+ and the
      synthesized AuNPs exhibited aggregation on morphology. It was considered that
      chitosan DD and concentration played a more important role than MW in the size
      and shape of AuNPs.

PMID- 29050576
TI  - Chemical modification of xanthan in the ordered and disordered states: An open
      route for tuning the physico-chemical properties.
AB  - The impact of the chain stiffness on physicochemical properties has been studied
      by chemical modification of xanthan under both ordered and disordered
      conformations. Corresponding rheological properties were studied and results
      showed that amphiphilic xanthan exhibited completely different behaviors
      depending on its conformation during modification. Xanthan, when modified under
      ordered conformation, exhibits similar behavior to non-modified one, only the
      chain relaxation being strongly slowed down. Therefore, the high stiffness of
      xanthan helices does not allow hydrophobic moieties to associate. Oppositely,
      xanthan modified under its disordered conformation displayed a chemical gel-like
      behavior without any relaxation of the chain within the studied frequency range
      nor with temperature, which is unexpected for this length of alkyl chains. These
      different viscoelastic properties can be correlated to the regioselectivity of
      the grafting; the latter can be controlled by the conformation of xanthan during
      modification, thus by the synthesis conditions.

PMID- 29050577
TI  - Acid-base synergistic flame retardant wood pulp paper with high thermal
      stability.
AB  - Acid-catalytic degradation caused by acid source flame retardants is the main
      reason for a decline in thermal stability of flame-retarded lignocellulosic
      materials. In the present research, a guanidine phosphate (GP)/borax (BX) flame
      retardant system based on acid-base synergistic interaction was designed and used
      in wood pulp paper (WPP) to solve this problem. Results showed that the treated
      WPP obtained good flame retardancy with a limiting oxygen index (LOI) value of
      35.7%. As a basic flame retardant, borax could chemically combine with the acids
      released by guanidine phosphate, thus decreasing the acidity of the system in the
      initial heating stage. In this way, acid-catalytic degradation is greatly
      retarded on the lignocelluloses to improve thermal stability (the temperature of
      maximum degradation peak from 286 degrees C to 314 degrees C). Meanwhile, borax
      was also advantageous to form a denser and firmer condensed phase through
      reinforcement of the acid-base reaction product, borophosphates, allowing it to
      provide a protective barrier with higher quality.

PMID- 29050578
TI  - Antibacterial poly(ethylene oxide) electrospun nanofibers containing cinnamon
      essential oil/beta-cyclodextrin proteoliposomes.
AB  - A novel antibacterial packaging material was engineered by incorporating cinnamon
      essential oil/beta-cyclodextrin (CEO/beta-CD) proteoliposomes into poly(ethylene
      oxide) (PEO) nanofibers by electrospinning technique. Herein, PEO was a
      stabilizing polymer and used as electrospinning polymeric matrix for the
      fabrication of CEO/beta-CD proteoliposomes nanofibers. The nanoliposomes were
      inlaid with protein are defined as proteoliposomes. Taking advantage of bacterial
      protease secreted from Bacillus cereus (B. cereus), the controlled release of CEO
      from proteoliposomes was achieved via proteolysis of protein in proteoliposomes.
      The CEO/beta-CD inclusion complex was prepared by the aqueous solution method and
      characterized by Raman and FTIR spectroscopy. After the treatment of CEO/beta-CD
      proteoliposomes nanofibers packaging, the satisfactory antibacterial efficiency
      against B. cereus on beef was realized without any impact on sensory quality of
      beef. This study demonstrated that the CEO/beta-CD proteoliposomes nanofibers can
      significantly extend the shelf life of beef and have potential application in
      active food packaging.

PMID- 29050579
TI  - Synthesis, characterisation and physicochemical properties of hydrophobically
      modified inulin using long-chain fatty acyl chlorides.
AB  - A series of inulin derivatives were synthesized in aqueous solution using acyl
      chlorides with varying alkyl chain length (C10-C16). They were characterised
      using a number of techniques including MALDI TOF-MS, 1H NMR and FTIR and their
      degree of substitution determined. The solution properties of the hydrophobically
      modified inulins were investigated using dye solubilisation and surface tension
      and it was confirmed that the molecules aggregated in solution above a critical
      concentration (critical aggregation concentration, CAC). The value of the CAC was
      found to be reasonably consistent between the different techniques and was shown
      to decrease with increasing hydrophobe chain length. It was found that the C10,
      C12 and C14 derivatives formed stable oil-in-water emulsions and the emulsion
      droplet size decreased with increasing alkyl chain length. The C16 derivative was
      not able to produce stable oil-in-water emulsions; however, it was able to form
      stable water-in-oil emulsions. The fact that the derivatives are able to form
      micellar-like aggregates and stabilise emulsions makes them suitable candidates
      for the encapsulation and delivery of active compounds with potential application
      in food, cosmetic, personal care and pharmaceutical formulations.

PMID- 29050580
TI  - Influence of starch oxidation on the functionality of starch-gelatin based active
      films.
AB  - Biodegradable active films were prepared by casting, using corn starch, with
      differing oxidation degree, bovine gelatin, glycerol, as a plasticizer, and ethyl
      lauroyl arginate (LAE) as antimicrobial compound. The films were characterized as
      to their microstructure, physical properties and water affinity. Starch oxidation
      with sodium periodate (SP) greatly improved polymer compatibility and
      crosslinking, especially at 1:1 glucose:SP molar ratio, which promoted the films'
      strength (40-92%) and barrier capacity (33 and 40% reduction in water vapour and
      oxygen permeability, respectively in LAE-free films), while Maillard reactions
      promoted the film browning. LAE, with amino and carbonyl groups, participated in
      the condensation reactions, interfering in the network crosslinking. All films
      with LAE showed bactericidal effect against Listeria innocua and Escherichia coli
      and LAE free films with oxidized starch inhibited the growth of both bacteria by
      1-2 log CFU, due to the antimicrobial properties of Maillard compounds. Blend
      films with the most oxidized starch and gelatin containing LAE are promising
      materials for food packaging applications.

PMID- 29050581
TI  - Multivalent cations-triggered rapid shape memory sodium carboxymethyl
      cellulose/polyacrylamide hydrogels with tunable mechanical strength.
AB  - A novel multivalent cations-triggered shape memory hydrogels were synthesized in
      a one-pot method, and interpenetrating double network was formed by chemically
      cross-linked polyacrylamide (PAM) network and physically cross-linked sodium
      carboxymethyl cellulose network. The temporary shape was fixed by complexation
      between a native biopolymer, sodium carboxymethyl cellulose (CMC), and transition
      metal ions, specifically Fe3+, Ag+, Al3+, Cu2+, Ni2+, and Mg2+. In particular,
      CMC-Fe3+ hydrogel exhibits excellent shape fixity ratio (95%). Therefore, we
      chose PAM/CMC1.0-Fe3+ hydrogel as the model material and further investigated its
      shape recovery process. It was found that a wide range of molecules and anions
      could be applied to break off the temporary cross-links between CMC and Fe3+. The
      PAM/CMC composite hydrogels also exhibited excellent tunable mechanical
      properties. The mechanical properties of the composite hydrogel can be adjusted
      by changing the cross-linking densities. The presented strategy could enrich the
      construction as well as application of biopolymers based shape memory hydrogels.

PMID- 29050582
TI  - pH-sensitive carboxymethyl chitosan hydrogels via acid-labile ortho ester linkage
      for potential biomedical applications.
AB  - Hydrogel systems with favorable biocompatibility and biodegradability are of much
      interest for application in biomaterials and tissue engineering. In this study, a
      new ortho ester-based acid-labile crosslink agent with dual-epoxy end groups was
      synthesized and crosslinked with carboxymethyl chitosan (CMCS) at different molar
      ratios to prepare a series of pH-sensitive hydrogels for drug delivering.
      Doxorubicin (DOX) was then readily loaded into the hydrogels and the in vitro
      release profiles indicated that the release rate increased rapidly while pH
      decreased from 7.4 to 5.0, which is consistent with the degradation rate of these
      hydrogels at corresponding pH conditions. In addition, results from MTT assay and
      flow cytometry demonstrated that these CMCS-based hydrogels and their degradation
      products have no cytotoxicity against SH-SY5Y and 293T cells. Therefore, the
      prepared acid-labile hydrogels could be applied in tumorous drug delivery systems
      and peritumoral implantation therapy by further optimization.

PMID- 29050583
TI  - Characterization, antioxidant property and cytoprotection of exopolysaccharide
      capped elemental selenium particles synthesized by Bacillus paralicheniformis
      SR14.
AB  - Instead of using existing methods to chemically synthesize elemental selenium
      particles (CheSePs), which first require separating and purifying polysaccharides
      or proteins and adding extra reducing agent, this study applied a novel method to
      directly assemble exopolysaccharide-capped biogenic elemental selenium particles
      (EPS-BioSePs) by Bacillus paralicheniformis SR14 during the metabolic process.
      Characterization by energy dispersive X-ray spectrometry (EDX), scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron
      spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), size
      measurement and chemical composition analysis verified that EPS-BioSePs exhibited
      a monodispersed and homogeneous spherical structure 293.73+/-4.03nm in size.
      Compared to a widely used form of CheSePs stabilized and coated by bovine serum
      albumin, EPS-BioSePs exhibited better antioxidant properties on scavenging DPPH,
      superoxide and ABTS free radicals, but not hydroxyl radical. In vitro experiments
      with porcine jejunum epithelial (IPEC-J2) cells also indicated a significant
      cytoprotection of EPS-BioSePs against hydrogen peroxide-induced oxidative stress,
      as exhibited by cell viability reduction and suppression of ROS generation. These
      results suggested that this new form of selenium possessed great antioxidant
      property and cytoprotection and exopolysaccharide-producing bacteria could
      gradually become an appropriate choice to synthesize biogenic elemental selenium
      particles with potential applications as antioxidants.

PMID- 29050584
TI  - Molecular size is important for the safety and selective inhibition of intrinsic
      factor Xase for fucosylated chondroitin sulfate.
AB  - Fucosylated chondroitin sulfate from sea cucumber Isostichopus badionotus (FCS
      Ib) showed potent anticoagulant activities without selectivity. The present study
      focused on developing safe FCS-Ib oligomers showing selective inhibition of
      intrinsic factor Xase (anti-FXase) prepared through partial N-deacetylation
      deaminative cleavage. The N-deacetylation degree was regulated by reaction time,
      controlling the resulting oligomer distribution. Structure analysis confirmed the
      selectivity of degradation, and 12 high purity fractions with trisaccharide
      repeating units were separated. In vitro anticoagulant assays indicated a
      decrease in molecular weight (Mw) dramatically reduced activated partial
      thromboplastin time (APTT), thrombin time (TT), AT-dependent anti-FIIa and anti
      FXa activities, while the oligomers retained potent anti-FXase activity until
      they fell below 3kDa. Meanwhile, human FXII activation and platelet aggregation
      were markedly reduced with decreasing Mw and were moderate when under 12.0kDa.
      Thus, fragments of 3-12.0kDa should be safe and effective as selective inhibitors
      of intrinsic tenase complex for application as clinical anticoagulants.

PMID- 29050585
TI  - Non-cytotoxic hybrid bioscaffolds of chitosan-silica: Sol-gel synthesis,
      characterization and proposed application.
AB  - Biohybrid chitosan-silica scaffolds were synthesized through the sol-gel and the
      freeze drying processes. Hydrolysis and condensation of chitosan with
      tetraethylorthosilicate (TEOS) in the presence of 3-isocyanatopropyl
      triethoxysilane (ICPTES) were successfully carried out. Results obtained from
      FTIR, swelling test and pyrolysis confirmed that the hybrid scaffolds containing
      covalent coupling between the organic and inorganic networks were formed with
      high crosslink density of SiOSi bridging and could be classified as the class II
      material. The hybridization also resulted in improvements on mechanical strength
      and stability comparing to the pure chitosan. In vitro investigations on the
      guided bone regeneration and the cytotoxicity were also performed. SEM-EDS was
      used to examine the proliferation of calcium phosphate mineral at the scaffold
      surface after an immersion in simulated body fluid. The results revealed that the
      hybrid scaffolds exhibited a rapid induction of calcium phosphate mineral without
      cytotoxicity effect, reflecting an excellent in vitro bone bioactivity which was
      superior to the pure chitosan scaffold.

PMID- 29050586
TI  - Sodium alginate: A promising biopolymer for corrosion protection of API X60 high
      strength carbon steel in saline medium.
AB  - Sodium alginate (SA), a polysaccharide biopolymer, has been studied as an
      effective inhibitor against the corrosion of API X60 steel in neutral 3.5% NaCl
      using gravimetric and electrochemical techniques (OCP, EIS and EFM). The
      inhibition efficiency of the SA increased with concentration but was lower at
      higher temperature (70 degrees C). Electrochemical measurements showed that the
      SA shifted the steel corrosion potential to more positive value and reduced the
      kinetics of corrosion by forming an adsorbed layer which mitigated the steel
      surface wetting, based on contact angle measurement. SEM-EDAX was used to confirm
      the inhibition of SA on API X60 steel surfaces. The SA adsorbs on the steel
      surface through a physisorption mechanism using its carboxylate oxygen according
      to UV-vis and ATR-IR measurements, respectively. This phenomena result in
      decreased localized pitting corrosion of the API X60 steel in 3.5% NaCl solution.
      Theoretical results using quantum chemical calculations and Monte Carlo
      simulations provide further atomic level insights into the interaction of SA with
      steel surface.

PMID- 29050587
TI  - Hypoglycemic effect and mechanism of a pectic polysaccharide with hexenuronic
      acid from the fruits of Ficus pumila L. in C57BL/KsJ db/db mice.
AB  - In this study, a particular pectic polysaccharide (FPLP) was extracted and
      purified from the fruits of Ficus pumila Linn. through boiling water extraction,
      alcohol precipitation, diethylaminoethyl-Sepharose Fast Flow chromatography and
      SuperdexTM G-75 gel filtration chromatography. Analysis of high-performance gel
      permeation chromatography, FTIR, GC-MS, methylation and 1D/2D NMR spectroscopy
      revealed that FPLP (Mw: 34.69kDa) is a linear (1,4)-alpha-d-galacturonic acid
      binding 1.30% branched chain hexenuronic acid with 23.34% methyl esterification.
      Treatment with FPLP ameliorated hyperglycaemia in association with an improvement
      in hepatic glycogen metabolism in C57BL/KsJ db/db mice. The activation of IRS
      1/PI3K/Akt/GSK3beta/GS insulin signalling pathway and AMPK/GSK3beta/GS signalling
      pathway and the regulation of glucokinase, phosphoenolpyruvate carboxykinase and
      glucose-6-phosphatase expressions involved in hepatic glycogenesis and
      glycogenolysis were considered the therapeutic mechanisms of FPLP. These results
      provide a new insight for investigating the effects of pectic polysaccharides on
      blood glucose control and suggest that FPLP is a promising nutraceutical for
      treatment of T2DM.

PMID- 29050588
TI  - Sequential one-pot multienzyme synthesis of hyaluronan and its derivative.
AB  - Hyaluronan (HA) is a linear polysaccharide composed of repeating disaccharide
      units. It has been well documented to play an array of biological functions in
      cancer events. Here, we reported a sequential one-pot multienzyme (OPME) strategy
      for in vitro synthesis of HA and its derivatives. The strategy, which combined in
      situ sugar nucleotides generation with HA chain polymerization, could convert
      cheap monosaccharides into HA polymers without consuming exogenous sugar
      nucleotide donors. HA polymers (number-average molecular weight ranged from
      1.5*104 to 5.5*105Da) with over 70% yields were efficiently synthesized and
      purified from this one-pot system. More importantly, partial labeled HA
      derivative was further synthesized by metabolic incorporation of unnatural
      monosaccharide analogues into the sequential OPME system. Cross-linked HA
      hydrogel was achieved via copper (I)-catalyzed azide-alkyne cycloaddition and
      exhibited novel networks consisting of both inter- and intra-connected HA chains,
      which could facilitate the potential applications of this unique polysaccharide.

PMID- 29050589
TI  - Preparation, characterization, and properties of fluorine-free superhydrophobic
      paper based on layer-by-layer assembly.
AB  - A fluorine-free superhydrophobic paper was prepared by a facile method involving
      layer-by-layer deposition of cationic starch and sodium alginate together with
      subsequent modification of trichloromethylsilane has been reported in this
      article. The surface chemical compositions, potentials and surface morphologies
      of the modified papers were characterized, respectively. The wetting abilities
      and physical strength properties of the modified papers were investigated. After
      4-time deposition of cationic starch/sodium alginate bilayer followed by
      trichloromethylsilane treatment, the water contact angle of modified paper
      reached up to 161.7 degrees , and the tensile strength increased by 6.8% in
      comparison to that of pristine paper. This as-prepared superhydrophobic paper not
      only showed low bacterial adhesion property, self-cleaning behavior, water
      repellency, as well as high durability against deformation, chemical and time,
      but also kept a high strength property under high relative humidity condition,
      which might has a great application potential in the liquid paper packaging
      industry.

PMID- 29050590
TI  - Sugar-cane bagasse derived cellulose enhances performance of polylactide and
      polydioxanone electrospun scaffold for tissue engineering.
AB  - Bagasse is a waste product of sugar extraction from sugar-cane with approximately
      30% cellulose content. Cellulose was successfully extracted from sugar-cane
      bagasse using a modified mercerization-bleaching approach with a 40% yield.
      Extracted cellulose was converted to cellulose acetate for enhanced
      electrospinnability and blended with poly-l-Lactide or polydioxanone before
      solution electrospinning. Physico-chemical evaluation of the electrospun mats
      showed variable miscibility of blends. In vitro cell studies with L929 mouse
      fibroblast cells was quite conclusive as regards the biocompatibility of the
      blended mats with proliferative behavior of cells, extracellular matrix
      deposition and characteristic features of healthy cellular response. MTT assay
      indicated that the cellulose blended mats induced higher cell densities than the
      controls. Cellulose content influenced parameters such as fiber diameter,
      porosity and cell-matrix interaction of mats impacting on cell growth and
      behavior. Preliminary assessment of biomineralization potential of the mats by
      SEM showed nano-hydroxyapatite deposits on the electrospun fibers.

PMID- 29050591
TI  - Benign development of cotton with antibacterial activity and metal sorpability
      through introduction amino triazole moieties and AgNPs in cotton structure pre
      treated with periodate.
AB  - The research work presented herein was undertaken with a view to develop,
      characterize and highlight modified cotton fabrics that acquire durable
      antibacterial activity in concomitant with high metal sorption capacity. The
      development is based on reacting cotton cellulose previously oxidized by sodium
      periodate-with 4 amino-1,2,4 triazole in presence and absence of silver nano
      particles (AgNPs). The idea behind the periodate pretreatment is to convert (via
      oxidative cleavge) the 2,3-vicinal diol of the anhydroglucose units of cotton
      into aldehyde groups. The latter are easily reacting with the triazole groups in
      the modified cotton. On the other hand AgNPs were fabricated as per the reduction
      method using bio-material extracted from the root of licorice. By virtue of its
      reducing action, the bio-material converts Ag+ ions to Ag0 atom which is also
      stabilized Ag the bio-material in the form of cluster which is the agregate of
      about 5 Ag0. The clusters are cropped with the stabilizer thus forming silver
      nanoparticles. Measurement of the particle size displays a value of 8.7nm.
      Charactrisation of triazole treated cotton fabrics reveals the presence of the
      triazole moieties inside the structure of cotton. Furthermore, Fabrictreated with
      triazole in presence and absence of AgNPs exhibits a relatively high
      antibacterial activity against gram-negative tested bacteria (E. coli) as
      compared to that of gram-positive tested bacteria (S. aureus). The metal sorption
      of triazole treated cotton fabrics was higher than those of untreated or
      periodate pretreated fabric due to the increase in nitrogen centers created along
      the cellulose chains. Experimental data were accomplished through Langmuir,
      Freundlich and Temkin sorption isotherm models. It was shown that sorption
      follows Langmuir isotherm model and suggests that the innovative fabric in
      question can adsorb metal ions from polluted dye bath.

PMID- 29050592
TI  - Eco-friendly films prepared from plantain flour/PCL blends under reactive
      extrusion conditions using zirconium octanoate as a catalyst.
AB  - Plantain flour (Musa ssp., group AAB, sub-group clone Harton)/poly(epsilon
      caprolactone) (PCL) blends, containing glycerol as a plasticizer, were prepared
      by reactive extrusion (REx) in a twin-screw extruder using zirconium octanoate
      (Zr(Oct)4) as a catalyst, followed by thermo-compression molding for film
      development. The films were then characterized in terms of their: infrared (FTIR)
      spectra, water solubility, thermogravimetric (TGA) curves, differential scanning
      calorimetry (DSC) thermograms, and X-ray diffraction (XDR) diffractograms, as
      well as their microstructural, mechanical and antimicrobial properties in order
      to (1) compare the effects of PCLs with two different molecular weights (Mw) on
      the characteristics of the plantain flour/PCL blends, and (2) determine whether
      using Zr(Oct)4 in the production of active composite polymer materials improves
      their properties. The plantain flour/PCL blends were all developed successfully.
      The higher Mw PCL gave more hydrophobic and thermally stable films with improved
      mechanical properties. The addition of the Zr(Oct)4 catalyst to the plantain
      flour/PCL blends also resulted in films with similar characteristics to those
      described above, due to the cross-linking of the polymers. In addition, the films
      containing the catalyst showed antimicrobial activity against Escherichia coli
      O157:H7 and Staphylococcus aureus indicating a dual effect of Zr(Oct)4, and
      making it an attractive alternative for the development of active films.

PMID- 29050593
TI  - Optimization of aqueous pectin extraction from Citrus medica peel.
AB  - In this study, the effect of aqueous extraction conditions (temperature of 70-90
      degrees C, time of 60-180min, and liquid/solid ratio (LSR) of 20-40v/w) on the
      yield and degree of esterification (DE) of Citrus medica peel pectin was studied
      using a Box-Behnken design. The highest production yield of pectin (21.85+/
      0.35%) was obtained at temperature of 90 degrees C, extraction time of 180min and
      LSR of 40v/w as optimum extraction conditions which was close to the predicted
      value (24.13%). In these extraction conditions, the DE and the emulsifying
      activity were 77.2 and 46.5%, respectively. Also, the emulsions were 90.30 and
      90% stable at 4 degrees C, and 83.87 and 83.50% at 25 degrees C after 1 and
      30days, respectively. The determination of flow behavior showed that the pectin
      solutions had a Newtonian behavior at low concentrations (0.1, 0.5 and 1.0%w/v),
      while in higher concentration (2.0%w/v), the pseudoplastic flow behavior became
      dominant.

PMID- 29050594
TI  - Novel bioactive surface functionalization of bacterial cellulose membrane.
AB  - Bacterial cellulose (BC) membrane is a promising biopolymer which can be used for
      tissue implants, wound healing, and drug delivery due to its unique properties,
      such as high crystallinity, high mechanical strength, ultrafine fiber network
      structure, good water holding capacity and biocompatibility. However, BC does not
      intrinsically present antibacterial properties. In the present study,
      functionalized BC membranes were prepared. FTIR, SEM and XPS were used to
      characterize the chemical composition and surface morphology. Static water
      contact angles were measured to investigate surface wettability. Escherichia
      coli, Staphylococcus aureus, Bacillus subtilis and Candida albicans were used to
      evaluate the antibacterial properties of membranes. HEK293 cell lines were
      applied to assess the biocompatibility of membrane surfaces by MTT assay and
      their morphologies were observed by Confocal Microscopy. Interestingly, the
      resultant functionalized BC membranes exhibiting excellent antibacterial property
      and good biocompatibility demonstrated great utility and potential as biomaterial
      materials.

PMID- 29050595
TI  - Mixtures of ionic liquids as more efficient media for cellulose dissolution.
AB  - The ability to dissolve cellulose, by using mixtures of ionic liquids, has been
      studied and compared with results obtained for the corresponding single ionic
      liquids. The ionic liquid mixtures tested were a 3:7mol/mol mixture of 1-ethyl-3
      methylimidazolium chloride ([C2mim]Cl) and 1-ethyl-3-methylimidazolium acetate
      ([C2mim][OAc]), and the eutectic mixture (i.e., a 5.1:4.9mol/mol ratio) of
      [C2mim]Cl and 1-butyl-3-methylimidazolium chloride (C4mim]Cl). The amount of
      dissolved cellulose was investigated at three different temperatures (323, 348,
      and 373K) for each system. The greatest amount of dissolved cellulose was
      obtained for the [C2mim]Cl+[C2mim][OAc] mixture, at 373K, and it was 40g per 100g
      of solvent. Moreover, attempts were made to lower the viscosity of the resulting
      systems and improve the dissolution capacity by addition of dimethylsulfoxide
      (DMSO) as co-solvent. Results showed that addition of DMSO at 50mol% allows the
      dissolution of even greater amounts of cellulose (up to 43g per 100g of solvent).
      To the best of our knowledge, this is the largest ever reported amount of
      dissolved cellulose in ionic liquid media. Additionally, physical properties
      (density, surface tension, and viscosity) of the investigated ionic liquid
      mixtures were determined and compared with the values of the corresponding parent
      salts. The dissolved cellulose could be easily reconstituted from its solution in
      ionic liquid mixtures by addition of water. The regenerated cellulose was
      characterized by powder X-ray diffraction (pXRD), thermogravimetric analysis
      (TGA), and optical microscopy. The analyses confirmed the conversion of the
      crystal structure of cellulose from cellulose I to cellulose II during the
      dissolution and regeneration process.

PMID- 29050596
TI  - Morphological, structural and functional properties of starch granules extracted
      from the tubers and seeds of Sphenostylis stenocarpa.
AB  - Sphenostylis stenocarpa (Hochst. ex A. Rich.) Harms, is a legume widely
      recognized in Africa for its edible starchy tuber and seeds. In the present
      morphological, structural and functional properties of starch extracted from the
      tubers and seeds of a same accession of this plant were characterized and
      compared. With smaller and more angular granules, tuber starch displayed higher
      resistance toward amylolysis and gelatinization than seed starch. The amylolysis
      of seed starch resulted in fragmented granules with typical layered structures of
      growth rings. During their hydrothermal treatments, both tuber and seed starches
      showed condensed ghosts even at 95 degrees C. This high resistance toward
      hydrothermal degradation was considered as the basis of the typical pasting
      properties of these two materials. Both seed and tuber starch exhibited A-type
      crystalline pattern. Under non-oxidative combustion tuber starch presented a
      degradation peak at 310 degrees C while seed starch was degraded around 302
      degrees C.

PMID- 29050597
TI  - An insight into the influence of hydrogen bond acceptors on cellulose/1-allyl-3
      methyl imidazolium chloride solution.
AB  - Although ionic liquids have been well established as effective solvents for the
      dissolution and processing of natural cellulose fibers, the detailed dissolution
      mechanism at the molecular level still remains unclear. Herein, the turbidimetric
      measurement showed that the solubility of cellulose in 1-allyl-3-methyl
      imidazolium chloride (AmimCl) decreased with increasing temperature. The
      temperature dependence of the OH stretching vibration band of cellulose in AmimCl
      was investigated by infrared spectroscopy. The interaction between AmimCl and
      different hydrogen bond acceptors were investigated by turbidimetry and NMR
      spectroscopy, which indicated that the excellent compatibility of the hydrogen
      bond acceptors with AmimCl provides more interaction sites for the hydroxyl
      groups of the cellulose. In addition, ionic liquids with a similar anionic
      structure of hydrogen bond acceptors have been synthesized. This study provides a
      green and safe guide for the preparation of ionic liquids with excellent
      solubility of cellulose.

PMID- 29050598
TI  - Improving molar mass analysis of cellulose samples with limited solubility.
AB  - Fully dissolved cellulose samples are a requirement for reliable size exclusion
      chromatography (SEC). Although most of the standard dissolving pulps can be
      completely dissolved in the N,N-dimethylacetamide/lithium chloride (DMAc/LiCl)
      solvent system, some cellulose samples (e.g., regenerated cellulose fibers) have
      poor solubility and therefore have a limited access to molar mass measurements.
      For improving the latter, different activation steps have been developed. In
      order to obtain complete solutions for subsequent SEC analysis, the scope of this
      study was to further improve established methods by elucidating the major
      influential factors of sample preparation. In addition, the degree of stretching
      in artificial fibers was examined for viscose fibers. Therefore, activation steps
      in DMAc or dimethyl sulfoxide (DMSO) and subsequent dissolution in DMAc/LiCl were
      analyzed with swelling and dissolution kinetics. The time needed for maximum
      swelling was found to be the optimum activation time. Turbidity measurement was
      introduced to observe dissolution kinetics as an indicator of dissolution
      quality. Thus, the duration, as well as the number of steps toward dissolution,
      was optimized to enhance the throughput in the overall analysis of a large
      variety of hitherto poorly soluble cellulose samples. A comparison of the MMDs of
      completely soluble reference materials obtained with the intensified conventional
      method, and the developed method demonstrated that the latter has no adverse
      influence on the results.

PMID- 29050599
TI  - Development of chitosan-sodium phytate nanoparticles as a potent antibacterial
      agent.
AB  - Chitosan nanoparticles have attracted considerable attention as a potential
      carrier for food and pharmaceutical applications. Herein, using natural sodium
      phytate as a gelation agent, we developed a new type of green and biocompatible
      chitosan nanoparticles. We discovered that the chitosan-sodium phytate
      nanoparticles exhibited potent antibacterial activities. The chitosan-sodium
      phytate nanoparticles prepared from low molecular weight (LMW, 140+/-7kDa) and
      medium molecular weight (MMW, 454+/-21kDa) chitosan were spherical. Under optimum
      conditions-with a ratio of LMW chitosan to sodium phytate of 24:1 and MMW
      chitosan to sodium phytate of 21:1-the sizes of the LMW and MMW chitosan
      nanoparticles were 20-80 and 80-100nm, respectively, as observed by transmission
      electron microscopy. The formation mechanism of chitosan nanoparticles occurred
      through both electrostatic interactions and hydrogen bonds. No cytotoxicity for
      normal liver cells was found in chitosan-sodium phytate nanoparticles measured by
      methyl thiazolyl tetrazolium assay. Furthermore, the antimicrobial assays
      indicated that the antimicrobial activity of the LMW chitosan nanoparticles was
      greater than that of MMW chitosan nanoparticles. The minimum inhibition
      concentration values and half inhibiting concentration of LMW chitosan-sodium
      phytate nanoparticles for Escherichia coli were 1.5 and 0.8mg/mL, respectively.
      In addition, the antimicrobial activity of chitosan nanoparticles against Gram
      negative bacteria was better than that against Gram-positive bacteria. The newly
      developed chitosan-sodium phytate nanoparticles could be used as a potential
      antibacterial agent.

PMID- 29050600
TI  - Evaluation of disulfide bond-conjugated LMWSC-g-bPEI as non-viral vector for low
      cytotoxicity and efficient gene delivery.
AB  - For efficient gene delivery, non-viral vectors should have high cellular uptake,
      excellent endosomal escape, and the ability to rapidly release the gene into the
      cytoplasm. Here, we developed a disulfide bond-conjugated bioreducible LMWSC-g
      bPEI (LCP) composed of low molecular-weight water soluble chitosan (LMWSC), bPEI,
      and cystamine (Cys). The developed LCP had advantages such as low toxicity, great
      endosomal escape, and rapid release of pDNA into the cytoplasm. The polyplexes
      with LCP showed higher uptake into the nucleus and greater transfection
      efficiency than that without disulfide bond. Moreover, LCP polymer and polyplexes
      with LCP indicated lower cytotoxicity than bPEI 25kDa. In addition, a gel
      retardation assay and particle size were analyzed to demonstrate the reduction
      sensitive gene delivery system. Besides, intracellular uptake pathway of
      polyplexes was investigated by various endocytosis inhibitor and confirmed to
      internalization into cell via macropinocytosis. These results suggest that
      bioreducible LCP is a superb non-viral vector for efficient gene delivery.

PMID- 29050601
TI  - Preparation of cationized starch from food industry waste biomass and its
      utilization in sulfate removal from aqueous solution.
AB  - In this work, untreated starch-rich potato peel waste was used as a starting
      material in preparation of cationized starch (CS)1 in water solution with 2
      chloro-3-hydroxypropyltrimethylammonium chloride (CHPTAC) as the cationization
      reagent. The impact of various factors (activation time, temperature, reaction
      time, the amount of CHPTAC and NaOH) on the degree of substitution (DS) of CS was
      studied by using experimental design. The DS values were determined by 1H NMR.
      The highest DS (0.40) was obtained when the reaction time was 8h, temperature 30
      degrees C, the molar ratio of CHPTAC and NaOH to AGU 3 and 3.75, respectively.
      The prepared CS was successfully used to remove sulfate ions from an aqueous
      solution with ultrafiltration technique. Sulfate is a major pollutant of water
      bodies so development of efficient techniques for its removal is detrimental. The
      removal of sulfate in study was 74% at best.

PMID- 29050602
TI  - Fabrication of porous chitosan membranes composed of nanofibers by low
      temperature thermally induced phase separation, and their adsorption behavior for
      Cu2.
AB  - Low temperature thermally induced phase separation (LT-TIPS) of chitosan solution
      was developed to fabricate porous chitosan membranes (p-CSMs), which were
      composed of short nanofibers with diameter of 40-60nm. Compared to the
      conventional acetic acid/water solvent, a mixed solvent of acetic
      acid/ethanol/water was used to prepare chitosan solution. The effect of solvent
      composition, quenching temperature and time, and coagulant on the p-CSM
      morphology were systematically explored. The optimum conditions for fabricating p
      CSM was to quench 2% chitosan/2% acetic acid in water/ethanol (70/30) at -20
      degrees C for 12h, followed by coagulating in 1% Na2CO3 in water/ethanol (50/50).
      The p-CSM was an effective adsorbent for Cu2+ and had a Langmuir adsorption
      capacity of 2.57mmol/g, which is close to the adsorption capacity of natural and
      electrospun chitosan nanofibers. The p-CSM maintained 90% adsorption efficiency
      for Cu2+ even after six cycles.

PMID- 29050603
TI  - The mechanism for cleavage of three typical glucosidic bonds induced by hydroxyl
      free radical.
AB  - A novel mechanism for cleavage of three typical alpha(1->2), alpha(1->4) and
      beta(1->4) glucosidic bonds induced by hydroxyl free radical was examined with
      DFT theory at B3LYP/6-31+G(d,p) level using PCM water solvent model. It was found
      that the hydrogen abstraction from the CH bonds outside the saccharide rings
      could induce the hydrogen transfer from the hydroxyl at the radical carbon to the
      oxygen atom of saccharide ring with the mediation of water, which led to the
      opening of saccharide ring and the breakage of glucosidic bonds. Alternatively,
      the hydrogen in COH outside the saccharide ring of maltose and sucrose could also
      transfer to the adjacent glucosidic oxygen atom with a water molecule mediation
      to make glucosidic bond break directly. Based on this study, it can be well
      explained the experimental results that the oxidation of some oligosaccharides
      with hydroxyl free radicals can produce molecules of glucose, fructose and other
      monosaccharides.

PMID- 29050604
TI  - Chitosan as an effective inhibitor of multidrug resistant Acinetobacter
      baumannii.
AB  - Over the last two decades worldwide levels of antibiotic resistance have risen
      leading to the appearance of multidrug resistant microorganisms. Acinetobacter
      baumannii is a known skin pathogen which has emerged as a major cause of
      nosocomial outbreaks due to its capacity to colonize indwelling medical devices
      and natural antibiotic resistance. With chitosan being an effective antimicrobial
      agent against antibiotic resistant microorganisms, the aim of this work was to
      access its potential as an alternative to traditional antimicrobials in the
      management of A. baumannii growth. What the results showed was that both chitosan
      MW's tested were active upon A. baumannii's planktonic and sessile growth. For
      planktonic growth MICs and MBCs were obtained at relatively low concentrations
      (0.5-2mg/mL) while for sessile growth chitosan proved to be an effective
      inhibitor of A. baumannii's adhesion and biofilm formation. Considering these
      results chitosan shows a high potential for control of A. baumannii infections.

PMID- 29050605
TI  - Isolation of cellulose-II nanospheres from flax stems and their physical and
      morphological properties.
AB  - In this study, cellulose-II nanospheres (CNS) were extracted from flax fibers and
      analyzed to understand the crystalline, functional and morphological properties
      by means of X-ray Diffraction (X-RD), Fourier Transform Infrared (FT-IR) and
      Scanning Electron Microscopy (SEM). FT-IR and SEM results indicate the effective
      removal of extractives, lignin and hemicellulose. X-RD results clearly show the
      transformation from cellulose-I to cellulose-II during the mercerization process.
      Further, the resulting cellulose fibers were treated with sulfuric acid in order
      to obtain cellulose nanospheres (CNS). The morphology was measured by SEM,
      Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM). The
      size distribution and the surface charge of CNS were investigated by Small-Angle
      X-ray Scattering (SAXS) and Nanosizer. The results indicate a size distribution
      of CNS between 20 and 90nm moderately dispersed. Finally, the transversal elastic
      modulus of CNS-II was determined by using AFM, and results reveal the range
      varying from 6 to 25GPa.

PMID- 29050606
TI  - Chemical property and impacts of different polysaccharide fractions from Fructus
      Mori. on lipolysis with digestion model in vitro.
AB  - Three polysaccharides (MFP-1, MFP-2, and MFP-3) were fractioned from mulberry
      fruits with 30%, 60%, and 90% (v/v) ethanol, respectively. The MFP-1 had the
      largest molecular weight of 838kDa, followed by MFP-2 from 49.5 to 163kDa, and
      then MFP-3 from 1.41 to 15.30kDa. The three polysaccharides were composed of
      arabinose, galactose, glucose, mannose, xylose, and galacturonic acid but with
      different molar ratio. They also exhibited different surface morphology and
      thermogravimetric properties. In addition, the impact of the three
      polysaccharides on the digestion of lipid in a simulated saliva and
      gastrointestinal tract was investigated. The results indicated MFP-2 had the
      strongest ability to reduce the rate and extent of lipid digestion. These results
      have important implications for understanding the influence of polysaccharides on
      lipid digestion. The effect on retarding lipid digestion within the
      gastrointestinal tract might be important for the development functional food
      rich in oil to promote health.

PMID- 29050607
TI  - Physical and functional properties of pectin-fish gelatin films containing the
      olive phenols hydroxytyrosol and 3,4-dihydroxyphenylglycol.
AB  - This study describes the development of a composite edible film based on pectin
      and fish skin protein capable of protecting food from microbial attack and
      oxidative degradation. The film was prepared with glycerol as plasticizer and the
      antioxidant and antimicrobial phenolic compounds hydroxytyrosol (HT) and 3,4
      dihydroxyphenylglycol (DHPG), extracted from olive fruit, as active agents. The
      influence of the concentration of plasticizer and active HT/DHPG on the
      mechanical and functional properties of the films was investigated, with values
      of water vapor permeability (WVP) between 0.13-0.22gmm/hm2kPa and oxygen
      permeability (OP) between 9.91-40.76cm3MUm/m2dkPa. The release behavior in water
      at different pH values was also evaluated. The antimicrobial capacity of the
      novel food coating was tested on strawberries, a fruit with high perishability.
      The bioactive edible film containing HT/DHPG preserved the strawberries against
      mold during storage with a significant delay in visible decay.

PMID- 29050608
TI  - Magnetic nanohydrogel obtained by miniemulsion polymerization of poly(acrylic
      acid) grafted onto derivatized dextran.
AB  - This study describes the synthesis of magnetic nanohydrogels by miniemulsion
      polymerization technique. Dextran was derivatized by the glycidyl methacrylate to
      anchor vinyl groups on polysaccharides backbone, allowing its use as a
      macromonomer for miniemulsion polymerization, as confirmed by proton nuclear
      magnetic resonance spectroscopy (13C NMR). Magnetite nanoparticles were
      synthesized by coprecipitation, followed by air oxidation to maghemite. The
      results of X-ray diffractometry (XRD), Raman and transmission electron microscopy
      (TEM) analysis showed that maghemite nanoparticles were obtained with a diameter
      of 5.27nm. The entrapment of iron oxide nanoparticles in a dextran nanohydrogel
      matrix was confirmed by thermogravimetric analysis (TGA), scanning transmission
      electron microscopy (STEM) and Zeta potential data. The magnetic nanohydrogels
      presented superparamagnetic behavior and were colloidal stable in physiological
      during 30days. Our findings suggest that the synthesized magnetic nanohydrogel
      are potential candidates for use in drug delivery systems due to its
      physicochemical and magnetic properties.

PMID- 29050609
TI  - Isolation, purification and structural characterization of a new water-soluble
      polysaccharide from Eremurus stenophyllus (boiss. & buhse) baker roots.
AB  - A new water-soluble polysaccharide (ESPS-1), with the average molecular weight of
      52.1kDa and a specific optical rotation of +169.7 degrees  (c 1.0, H2O), was
      successfully isolated by warm-water extraction and then purified using DEAE
      Cellulose and Sephadex G-100 columns from the roots of Eremurus stenophyllus. The
      results from chemical and instrumental tests including FT-IR, methylation and GC
      MS analysis, periodate oxidation and Smith degradation, partial acid hydrolysis,
      and NMR spectroscopy (1H, 13C, 1H-1H COSY, HMQC and HMBC) demonstrated that ESPS
      1 was a 2-O-acetylgalactan, composed of galactose, arabinose and mannose in a
      molar ratio of about 10:3:1, respectively. It has a backbone of (1->6)-alpha-d
      galactopyranosyl residues, with branches at O-3 consisting of alpha-d-Manp-(1->3)
      alpha-l-Araf-(1->3)-alpha-l-Araf-(1->3)-alpha-l-Araf-(1->. The acetyl groups are
      substituted at O-2 of (1->6)-linked Galp and the degree of acetylation was about
      14%.

PMID- 29050610
TI  - Performance improvements of the BNC tubes from unique double-silicone-tube
      bioreactors by introducing chitosan and heparin for application as small-diameter
      artificial blood vessels.
AB  - In order to improve property of bacterial nano-cellulose (BNC) to achieve the
      requirements of clinical application as small caliber vascular grafts, chitosan
      (CH) was deposited into the fibril network of the BNC tubes fabricated in unique
      Double-Silicone-Tube bioreactors. Heparin (Hep) was then chemically grafted into
      the BNC-based tubes using EDC/NHS crosslinking to improve performance of
      anticoagulation and endothelialization. Physicochemical and mechanical property,
      blood compatibility, and cytocompatibility were compared before and after
      compositing. The results indicated that strength at break was increased but burst
      pressure decreased slightly after compositing. Performance of the BNC tubes was
      improved remarkably after introducing chitosan and heparin. The EDC/NHS
      crosslinking catalyzed both amide bonds and ester bonds formation in the BNC/CH
      Hep composites. Three-dimensional surface structure and roughness were firstly
      obtained and discussed in relation to the hemocompatibility of BNC-based tubes.
      This work demonstrates the heparinized BNC-based tubes have great potential in
      application as small-diameter vascular prosthesis.

PMID- 29050611
TI  - Structure and in vitro anticancer activity of sulfated O-polysaccharide from
      marine bacterium Poseidonocella pacifica KMM 9010T.
AB  - We presented the structure of the sulfated polysaccharide moiety and anticancer
      activity in vitro of the O-deacylated lipopolysaccharide (DPS) isolated from the
      marine bacterium Poseidonocella pacifica KMM 9010T. The structure of O
      polysaccharide was investigated by chemical methods along with 1H and 13C NMR
      spectroscopy. The O-polysaccharide was built up of sulfated disaccharide
      repeating units consisted of d-rhamnose (d-Rhar) and 3-deoxy-d-manno-oct-2
      ulosonic acid (Kdop): ->7)-beta-Kdor4Ac5S-(2->3)-beta-d-Rhar2S-(1->. We
      demonstrated that the DPS from P. pacifica KMM 9010T non-toxic for normal mouse
      epidermal cells (JB6 Cl41 cell line) and inhibited colony formation of human
      colorectal carcinoma HT-29, breast adenocarcinoma MCF-7 and melanoma SK-MEL-5
      cells in a dose-dependent manner.

PMID- 29050612
TI  - Preparation and characterization of amorphous granular potato starches (AGPS) and
      cross-linked amorphous granular potato starches (CLAGPS).
AB  - Amorphous granular potato starch (AGPS) was prepared through heat treatment of
      native potato starch (NPS) at 94 degrees C with 53% EtOH, while cross-linked
      amorphous granular potato starch (CLAGPS) was prepared through cross-linking of
      NPS with sodium trimetaphosphate/sodium tripolyphosphate (STMP/STPP, 99:1) and
      heat treatment. Light and polarized microscopy showed that both AGPS and CLAGPS
      maintained their granule shapes but lost birefringence. DSC and XRD of both AGPS
      and CLAGPS also revealed complete gelatinization. On the other hand, CLAGPS
      exhibited no RVA pasting viscosity and AGPS had a higher final viscosity than NPS
      or CLAGPS. AGPS had a higher RS content than gelatinized potato starch, while
      that of CLAGPS did not increase, despite the cross-linking modification. Thus,
      AGPS and CLAGPS had distinct physicochemical properties from each other and from
      NPS, suggesting their potential applicability to the food, textile, and paper
      industries.

PMID- 29050613
TI  - Improvement of alkali efficiency for purification of dissolving pulp by a
      modified cold caustic extraction process.
AB  - In this study, a reutilization of caustic lye during cold caustic extraction
      (i.e., CCE) process to produce high-purity dissolving pulp and high-concentrated
      hemicellulose solution was proposed. The results showed that the lye can be
      reused about 12 times for producing high-purity dissolving pulps. With the number
      of CCE stages of 12, the hemicellulose in the lye can be auto-concentrated to
      about 37g/L. The alkali efficiency of the modified CCE process was about 6 (or 3)
      times better than the traditional CCE process with low- (or middle-) consistency
      of pulps. Therefore, the present process is feasible to be used for the
      purification of dissolving pulps with a cost-effective manner.

PMID- 29050614
TI  - The chemical-free production of nanocelluloses from microcrystalline cellulose
      and their use as Pickering emulsion stabilizer.
AB  - This paper takes a comparative approach in characterizing two types of nano-scale
      cellulosic particles obtained using chemical-free pathways, either by
      nearcritical water treatment or by high-shear homogenization from the same
      microcrystalline cellulose (MCC). The nearcritical water treatment efficiently
      depolymerized cellulose, producing a solid precipitated fraction of low-molecular
      weight material containing cellulose II, while homogenization mechanically
      deconstructed MCC without altering its molecular structure. Both pathways yielded
      nanocellulose-like materials yet with different morphologies. The mechanically
      produced, rod-like particles were obtained with high yield. In contrast, the
      hydrothermal precipitate exhibited more hydrophobic ribbon-like particles that
      provided a greater level of particle-particle interaction. Both materials
      successfully acted as stabilizers for oil-in-water Pickering emulsions; however,
      the hydrothermally-produced material exhibited superior performance, with stable
      emulsions obtained upon addition of as low as 1.0wt.% cellulose. These two
      pathways are highly relevant for altering the structure and properties of MCC and
      for formulating new, sustainably produced nanocellulose-based materials.

PMID- 29050615
TI  - Investigation of optimal conditions for production of highly crystalline
      nanocellulose with increased yield via novel Cr(III)-catalyzed hydrolysis:
      Response surface methodology.
AB  - For the first time, a highly efficient Cr(NO3)3 catalysis system was proposed for
      optimization the yield and crystallinity of nanocellulose end product. A five
      level three-factor central composite design coupled with response surface
      methodology was employed to elucidate parameters interactions between three
      design factors, namely reaction temperature (x1), reaction time (x2) and
      concentration of Cr(NO3)3 (x3) over a broad range of process conditions and
      determine the effect on crystallinity index and product yield. The developed
      models predicted the maximum nanocellulose yield of 87% at optimum process
      conditions of 70.6 degrees C, 1.48h, and 0.48M Cr(NO3)3. At these conditions, the
      obtained nanocellulose presented high crystallinity index (75.3%), spider-web
      like interconnected network morphology with the average width of 31.2+/-14.3nm.
      In addition, the yielded nanocellulose rendered a higher thermal stability than
      that of original cellulosic source and expected to be widely used as
      reinforcement agent in bio-nanocomposites materials.

PMID- 29050616
TI  - From 2D to 3D: The morphology, proliferation and differentiation of MC3T3-E1 on
      silk fibroin/chitosan matrices.
AB  - It has been widely accepted that cell culture in two-dimensional (2D) conditions
      may not be able to represent growth in three-dimensional (3D) conditions.
      Systematic comparisons between 2D and 3D cell cultures are needed to
      appropriately use the existing 2D results. In this work, we conducted a
      comparative study between 2D and 3D cell cultures of MC3T3-E1 using the same type
      of material (a mixture of silk fibroin (SF) and chitosan (CS)). Our results
      showed 3D SF/CS scaffold exhibited different effects on cell culture compared
      with the 2D cases. 1) The cells grown in 3D scaffold showed multiple
      morphologies. 2) The proliferation of cells in 3D scaffold was long-term and
      sustainable. 3) Cell differentiation occurred throughout the entire 3D scaffold.
      The results showed that cell culture in 3D SF/CS scaffold exhibited different
      features than 2D cases and 3D SF/CS scaffold could be a promising material for 3D
      cell culture.

PMID- 29050617
TI  - Sodium and acidic alginate foams with hierarchical porosity: Preparation,
      characterization and efficiency as a dye adsorbent.
AB  - A novel approach for the preparation of sodium alginate foams by ice-templating,
      followed by freeze-drying was described. Important effects of the preparation
      parameters on the macroporous structure of the final materials could be
      evidenced. A functionalization procedure for the preparation of acidified
      macro/meso-porous foams with high surface area was optimized and the efficiency
      of one alginic acid foam was demonstrated for the adsorption of a basic dye
      (methylene blue) from aqueous solution. The comparison of the maximum monolayer
      adsorption capacity of this adsorbent with the values already reported for other
      biosorbents clearly identified alginic acid foams as competitive sorbents for the
      removal of methylene blue from aqueous solutions.

PMID- 29050618
TI  - Degradation regulated bioactive hydrogel as the bioink with desirable moldability
      for microfluidic biofabrication.
AB  - Bioink development is vital in biofabriacation for generating three-dimensional
      (3D) tissue-like constructs. As potential candidates of bioinks, hydrogels need
      to meet the requirements of good moldability, initially strong mechanical
      properties and prominent bioactivity to guarantee cell vitality and further
      assembly. Enzyme-induced dynamic degradation is an efficient and biocompatible
      approach to improve the bioactivity of hydrogels through releasing space
      continuously for cell proliferation and promoting the functional establishing of
      engineered tissue. Here a novel bioink was designed by introducing alginate lyase
      into composite Alginate-GelMA hydrogels. Results showed that bioink with proper
      lyase content exhibited desirable modability and cytocompatibility. Then cell
      laden osteon-like microfibers were engineered with the microfluidic device and
      diverse complex 3D constructs were also successfully assembled. This degradation
      regulated bioink showed great promise in a variety of applications in tissue
      engineering and biomedical investigation.

PMID- 29050619
TI  - Novel starch based emulsion gels and emulsion microgel particles: Design,
      structure and rheology.
AB  - Novel starch-based emulsion microgel particles were designed using a facile top
      down shear-induced approach. The emulsion droplets were stabilized using octenyl
      succinic anhydride (OSA) modified starch and incorporated into heat-treated and
      sheared native starch gels, forming emulsion gels. Using gelation kinetics and
      small deformation rheological measurements of sheared native starch gels and
      emulsion gels, OSA starch-stabilized emulsion droplets were demonstrated to act
      as "active fillers". By varying native starch concentrations (15-20wt%) and oil
      fractions (5-20wt%), optimal concentrations for the formation of emulsion
      microgel particles were identified. Microscopy at various length scales
      (transmission confocal laser scanning and cryo-scanning electron microscopy) and
      static light scattering measurements revealed emulsion microgel particles of 5
      50MUm diameter. These novel emulsion microgel particles created via careful
      combination of gelatinized native starch and OSA stabilised-emulsion droplets
      acting as active fillers may find applications in food and personal care
      industries for delivery of lipophillic molecules.

PMID- 29050620
TI  - Safe therapeutics of murine melanoma model using a novel antineoplasic, the
      partially methylated mannogalactan from Pleurotus eryngii.
AB  - A heteropolysaccharide was isolated by cold aqueous extraction from edible
      mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological
      properties were evaluated. Structural assignments were carried out using mono-
      and bidimensional NMR spectroscopy, monosaccharide composition, and methylation
      analyses. A mannogalactan having a main chain of (1->6)-linked alpha-d
      galactopyranosyl and 3-O-methyl-alpha-d-galactopyranosyl residues, both partially
      substituted at OH-2 by beta-d-Manp (MG-Pe) single-unit was found. Biological
      effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine
      melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells
      invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up
      to 10days decreased in 60% the tumor volume compared to control. Additionally, no
      changes were observed when biochemical profile, complete blood cells count (CBC),
      organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti
      melanoma molecule capable of switching melanoma cells to a non-invasive phenotype
      with no toxicity to melanoma-bearing mice.

PMID- 29050622
TI  - Fixing the Valve, But Injuring the Kidneys, With Transcatheter Aortic Valve
      Replacement: Collateral Damage With Serious Consequences.

PMID- 29050621
TI  - Association of Chronic Kidney Disease With In-Hospital Outcomes of Transcatheter
      Aortic Valve Replacement.
AB  - OBJECTIVES: This study sought to determine the association of chronic kidney
      disease (CKD) with in-hospital outcomes of transcatheter aortic valve replacement
      (TAVR). BACKGROUND: CKD is a known independent risk factor for worse outcomes
      after surgical aortic valve replacement (SAVR). However, data on outcomes of
      patients with CKD undergoing TAVR are limited, especially in those on chronic
      dialysis. METHODS: The authors used data from the 2012 to 2014 National Inpatient
      Sample database to identify all patients >=18 years of age who underwent TAVR.
      International Classification of Diseases-Ninth Revision-Clinical Modification
      codes were used to identify patients with no CKD, CKD (without chronic dialysis),
      or end-stage renal disease (ESRD) on long-term dialysis. Multivariable logistic
      regression models were constructed using generalized estimating equations to
      examine in-hospital outcomes. RESULTS: Of 41,025 patients undergoing TAVR from
      2012 to 2014, 25,585 (62.4%) had no CKD, 13,750 (33.5%) had CKD, and 1,690 (4.1%)
      had ESRD. Compared with patients with no CKD, in-hospital mortality was
      significantly higher in patients with CKD or ESRD (3.8% vs. 4.5% vs. 8.3%;
      adjusted odds ratio [no CKD as reference]: 1.39 [95% confidence interval: 1.24 to
      1.55] for CKD and 2.58 [95% confidence interval: 2.09 to 3.13] for ESRD).
      Patients with CKD or ESRD had a higher incidence of major adverse cardiovascular
      events (composite of death, myocardial infarction, or stroke), net adverse
      cardiovascular events (composite of major adverse cardiovascular events, major
      bleeding, or vascular complications), and pacemaker implantation compared with
      patients without CKD. Acute kidney injury (AKI) and AKI requiring dialysis were
      associated with several-fold higher risk-adjusted in-hospital mortality in
      patients in the no CKD and CKD groups. Moreover, the incidence of AKI and AKI
      requiring dialysis did not decline during the study period. CONCLUSIONS: Patients
      with CKD or ESRD have worse in-hospital outcomes after TAVR. AKI is associated
      with higher in-hospital mortality in patients undergoing TAVR and the incidence
      of AKI has not declined over the years.

PMID- 29050624
TI  - The Plan Was to Replace the Valve, Not the Kidneys.

PMID- 29050623
TI  - Death and Dialysis After Transcatheter Aortic Valve Replacement: An Analysis of
      the STS/ACC TVT Registry.
AB  - OBJECTIVES: The authors sought to elucidate the true incidence of renal
      replacement therapy (RRT) after transcatheter aortic valve replacement (TAVR).
      BACKGROUND: There is a wide discrepancy in the reported rate of RRT after TAVR
      (1.4% to 40%). The true incidence of RRT after TAVR is unknown. METHODS: The
      STS/ACC TVT (Society of Thoracic Surgeons/American College of Cardiology
      Transcatheter Valve Therapy) registry was linked to the Centers for Medicare &
      Medicaid database to identify all patients that underwent TAVR from November 2011
      through September 2015 and their outcomes. The authors compared rates of death,
      new RRT, and a composite of both as a function of pre-procedure glomerular
      filtration rate (GFR), both in stages of chronic kidney disease (CKD), as well as
      on a continuous scale. RESULTS: Pre-procedure GFR is associated with the risk of
      death and new RRT after TAVR when GFR is <60 ml/min/m2, and increases
      significantly when GFR falls below 30 ml/min/m2. Incremental increases in GFR of
      5 ml/min/m2 were statistically significant (unadjusted hazard ratio: 0.71; p <
      0.001) at 30 days, and continued to be significant at 1 year when pre-procedure
      GFR was <60 ml/min/m2. One in 3 CKD stage 4 patients will be dead within 1 year,
      with 14.6% (roughly 1 in 6) requiring dialysis. In CKD stage 5, more than one
      third of patients will require RRT within 30 days; nearly two-thirds will require
      RRT at 1 year. CONCLUSIONS: In both unadjusted and adjusted analysis, pre
      procedural GFR was associated with the outcomes of death and new RRT. Increasing
      CKD stage leads to an increased risk of death and/or RRT. Continuous analysis
      showed significant differences in outcomes in all levels of CKD when GFR was <60
      ml/min/m2. Pre-procedure GFR should be considered when selecting CKD patients for
      TAVR.

PMID- 29050626
TI  - A Comparison of the ACURATE Neo and Sapien 3 Valves: Making Progress.

PMID- 29050625
TI  - Multicenter Comparison of Novel Self-Expanding Versus Balloon-Expandable
      Transcatheter Heart Valves.
AB  - OBJECTIVES: This study sought to compare 2 next-generation transcatheter heart
      valves (THV), the self-expanding ACURATE neo (NEO) and the balloon-expandable
      SAPIEN 3 (S3), in terms of device failure and early safety at 30 days.
      BACKGROUND: Deployment of these THV showed promising initial clinical results.
      However, no comparative data are available. METHODS: Of 1,121 treated patients at
      3 centers, a 1-to-2 nearest neighbor matching was performed to identify 2
      patients treated with S3 (n = 622) for each patient treated with NEO (n = 311).
      RESULTS: In-hospital complications were comparable between NEO and S3, including
      stroke (1.9% vs. 2.4%; p = 0.64), major vascular complications (10.3% vs. 8.5%; p
      = 0.38), or life-threatening bleeding (4.2% vs. 3.7%; p = 0.72). Device failure
      with NEO was comparable with S3 (10.9% vs. 9.6%; odds ratio: 1.09 [95% confidence
      interval: 0.69 to 1.73]; p = 0.71) with more paravalvular leakage (PVL II+, 4.8%
      vs. 1.8%; p = 0.01), but less elevated gradients (>=20 mm Hg, 3.2% vs. 6.9%; p =
      0.02) and pacemaker implantations (9.9% vs. 15.5%; p = 0.02). Thirty-day
      mortality (2.3% vs. 1.9%; p = 0.74) and the early safety composite endpoint
      (15.8% vs. 15.6%; hazard ratio: 0.97 [95% confidence interval: 0.68 to 1.39]; p =
      0.88) were similar with NEO and S3. CONCLUSIONS: Very high success rates were
      achieved for both valves, and the clinical and procedural results were
      comparable. Compared with S3, NEO was associated with less new pacemaker
      implantations and less elevated gradients, but with more paravalvular leakage.

PMID- 29050628
TI  - The Results of Transcatheter Aortic Valve Replacement Continue to Improve: The
      Specific Example of a Self-Expandable Transcatheter Heart Valve in a Real-Life
      Registry.

PMID- 29050627
TI  - Outcomes for the Commercial Use of Self-Expanding Prostheses in Transcatheter
      Aortic Valve Replacement: A Report From the STS/ACC TVT Registry.
AB  - OBJECTIVES: The authors sought to compare the outcomes of commercial
      transcatheter aortic valve replacement (TAVR) with the repositionable Evolut R
      platform to those observed with the CoreValve device in the Society of Thoracic
      Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy
      (TVT) Registry. BACKGROUND: TAVR continues to evolve, with rapid adoption of
      iterative changes for commercial practice. Insight into the outcomes of this
      adoption is needed. METHODS: Patients in the TVT Registry who had TAVR using a 23
      , 26-, or 29-mm self-expanding prosthesis were enrolled. Site-reported events for
      procedural, in-hospital, and 30-day outcomes were examined. RESULTS: Between
      January 2014 and April 2016, 9,616 patients underwent TAVR with a self-expanding
      prosthesis with data entered in the TVT Registry. Compared with patients treated
      with CoreValve TAVR, those who received Evolut R TAVR had a lower STS-PROM score
      (8.0 +/- 5.4% vs. 8.7 +/- 5.3%; p < 0.001), more iliofemoral access (91.6% vs.
      89.2%; p < 0.001), and more frequently had conscious sedation (27.4% vs. 12.7%; p
      < 0.001). With Evolut R TAVR, there was less need for a second prosthesis (2.2%
      vs. 4.5%; p < 0.001), less device migration (0.2% vs. 0.6%; p = 0.01), a lower
      incidence of moderate/severe paravalvular regurgitation (post-procedure, 4.4% vs.
      6.2%; p < 0.001), and shorter median hospital stay (4.0 vs. 5.0 days; p < 0.001).
      Patients treated with Evolut R TAVR had greater device success (96.3% vs. 94.9%;
      p = 0.001). At 30 days, Evolut R patients had both lower mortality (3.7% vs.
      5.3%; p < 0.001) and less need for a pacemaker (18.3% vs. 20.1%; p = 0.03).
      CONCLUSIONS: Commercial adoption of the Evolut R platform is associated with
      significant improvements in acute outcomes for patients undergoing TAVR for
      aortic stenosis.

PMID- 29050630
TI  - Trends in Lower Limb Revascularization Among Patients With End-Stage Renal
      Failure: Where Is the Journey Going, and How Far Have We Come?

PMID- 29050629
TI  - Nationwide Trends in Hospital Outcomes and Utilization After Lower Limb
      Revascularization in Patients on Hemodialysis.
AB  - OBJECTIVES: This study aimed to describe the temporal trends and outcomes of
      endovascular and surgical revascularization in a large, nationally representative
      sample of patients with end-stage renal disease on hemodialysis hospitalized for
      peripheral artery disease (PAD). BACKGROUND: PAD is prevalent among patients with
      end-stage renal disease on hemodialysis and is associated with significant
      morbidity and mortality. There is a paucity of information on trends in
      endovascular and surgical revascularization and post-procedure outcomes in this
      population. METHODS: We used the Nationwide Inpatient Sample (2002 to 2012) to
      identify hemodialysis patients undergoing endovascular or surgical procedures for
      PAD using diagnostic and procedural codes. We compared trends in amputation, post
      procedure complications, mortality, length of stay, and costs between the 2
      groups using trend tests and logistic regression. RESULTS: There were 77,049
      endovascular and 29,556 surgical procedures for PAD in hemodialysis patients.
      Trend analysis showed that endovascular procedures increased by nearly 3-fold,
      whereas there was a reciprocal decrease in surgical revascularization. Post
      procedure complication rates were relatively stable in persons undergoing
      endovascular procedures but nearly doubled in those undergoing surgery. Surgery
      was associated with 1.8 times adjusted odds (95% confidence interval: 1.60 to
      2.02) for complications and 1.6 times the adjusted odds for amputations (95%
      confidence interval: 1.40 to 1.75) but had similar mortality (adjusted odds
      ratio: 1.05; 95% confidence interval: 0.85 to 1.29) compared with endovascular
      procedures. Length of stay for endovascular procedures remained stable, whereas a
      decrease was seen for surgical procedures. Overall costs increased marginally for
      both procedures. CONCLUSIONS: Rates of endovascular procedures have increased,
      whereas those of surgeries have decreased. Surgical revascularization is
      associated with higher odds of overall complications. Further prospective studies
      and clinical trials are required to analyze the relationship between the severity
      of PAD and the revascularization strategy chosen.

PMID- 29050631
TI  - Drug-Coated Balloon Treatment for Femoropopliteal Artery Disease: The IN.PACT
      Global Study De Novo In-Stent Restenosis Imaging Cohort.
AB  - OBJECTIVES: This study sought to evaluate the safety and effectiveness of a
      paclitaxel-coated drug-coated balloon (DCB) for the treatment of patients with de
      novo in-stent restenosis (ISR). BACKGROUND: Treatment of patients with ISR
      remains a challenge. Current strategies are plagued by high rates of recurrent
      restenosis and need for reintervention. The best intervention for ISR remains to
      be elucidated. METHODS: The IN.PACT Global study is an independently adjudicated
      multicenter, prospective, single-arm study that enrolled 1,535 subjects with
      symptomatic atherosclerotic disease of the superficial femoral and/or popliteal
      arteries, including de novo ISR lesions. Patients enrolled in the pre-specified
      ISR imaging cohort were evaluated for vessel patency and reintervention within
      the 12-month follow-up period. RESULTS: A total of 131 subjects with 149 ISR
      lesions were included for analysis. The mean age of the cohort was 67.8 years.
      Mean lesion length was 17.17 +/- 10.47 cm, including 34.0% total occlusions and
      59.1% calcified lesions. The 12-month Kaplan-Meier estimate of primary patency
      was 88.7%. The rate of clinically driven target lesion revascularization (CD TLR)
      at 12 months was 7.3%. The primary safety outcome, a composite of freedom from
      device- and procedure-related mortality through 30 days and freedom from major
      target limb amputation and CD TLR within 12 months, was 92.7%. There were no
      major target limb amputations, no deaths, and a low (0.8%) thrombosis rate.
      CONCLUSIONS: Results from the ISR imaging cohort demonstrate high patency and a
      low rate of CD TLR at 12 months. These data confirm the safety and effectiveness
      of the IN.PACT Admiral DCB (Medtronic, Dublin, Ireland) in complex
      femoropopliteal lesions, including this challenging subset.

PMID- 29050632
TI  - Challenges of Stent Restenosis in Superficial Femoral and Popliteal Artery
      Disease.

PMID- 29050633
TI  - Successful Prevention of Inappropriate Cardiac Catheterizations by an Educational
      and Screening Program in a Tertiary Cardiac Referral Center.

PMID- 29050634
TI  - One Man's Vacation, Another Man's Stress Test.

PMID- 29050635
TI  - From the Editor's desk...: November 2017.

PMID- 29050637
TI  - Bipolar Disorder as a Mitochondrial Disease.

PMID- 29050638
TI  - Discussion of: "Follow-up trends after Emergency Department discharge for acutely
      symptomatic hernias".

PMID- 29050639
TI  - Myopericytoma of the tongue base: A case report.

PMID- 29050636
TI  - Targeting self-regulation to promote health behaviors in children.
AB  - Poor self-regulation (i.e., inability to harness cognitive, emotional,
      motivational resources to achieve goals) is hypothesized to contribute to
      unhealthy behaviors across the lifespan. Enhancing early self-regulation may
      increase positive health outcomes. Obesity is a major public health concern with
      early-emerging precursors related to self-regulation; it is therefore a good
      model for understanding self-regulation and health behavior. Preadolescence is a
      transition when children increase autonomy in health behaviors (e.g., eating,
      exercise habits), many of which involve self-regulation. This paper presents the
      scientific rationale for examining self-regulation mechanisms that are
      hypothesized to relate to health behaviors, specifically obesogenic eating, that
      have not been examined in children. We describe novel intervention protocols
      designed to enhance self-regulation skills, specifically executive functioning,
      emotion regulation, future-oriented thinking, and approach bias. Interventions
      are delivered via home visits. Assays of self-regulation and obesogenic eating
      behaviors using behavioral tasks and self-reports are implemented and evaluated
      to determine feasibility and psychometrics and to test intervention effects.
      Participants are low-income 9-12 year-old children who have been phenotyped for
      self-regulation, stress, eating behavior and adiposity through early childhood.
      Study goals are to examine intervention effects on self-regulation and whether
      change in self-regulation improves obesogenic eating.

PMID- 29050640
TI  - Gastrointestinal Tract Malignancies: Obstacles and Advancements.

PMID- 29050641
TI  - White matter pathways in persistent developmental stuttering: Lessons from
      tractography.
AB  - PURPOSE: Fluent speech production relies on the coordinated processing of
      multiple brain regions. This highlights the role of neural pathways that connect
      distinct brain regions in producing fluent speech. Here, we aim to investigate
      the role of the white matter pathways in persistent developmental stuttering
      (PDS), where speech fluency is disrupted. METHODS: We use diffusion weighted
      imaging and tractography to compare the white matter properties between adults
      who do and do not stutter. We compare the diffusion properties along 18 major
      cerebral white matter pathways. We complement the analysis with an overview of
      the methodology and a roadmap of the pathways implicated in PDS according to the
      existing literature. RESULTS: We report differences in the microstructural
      properties of the anterior callosum, the right inferior longitudinal fasciculus
      and the right cingulum in people who stutter compared with fluent controls.
      CONCLUSIONS: Persistent developmental stuttering is consistently associated with
      differences in bilateral distributed networks. We review evidence showing that
      PDS involves differences in bilateral dorsal fronto-temporal and fronto-parietal
      pathways, in callosal pathways, in several motor pathways and in basal ganglia
      connections. This entails an important role for long range white matter pathways
      in this disorder. Using a wide-lens analysis, we demonstrate differences in
      additional, right hemispheric pathways, which go beyond the replicable findings
      in the literature. This suggests that the affected circuits may extend beyond the
      known language and motor pathways.

PMID- 29050642
TI  - Editorial Comment.

PMID- 29050643
TI  - Measuring unintended effects in peacebuilding: What the field of international
      cooperation can learn from innovative approaches shaped by complex contexts.
AB  - Capturing unintended impacts has been a persistent struggle in all fields of
      international development, and the field of peacebuilding is no exception.
      However, because peacebuilding focuses on relationships in complex contexts, the
      field of peacebuilding has, by necessity, made efforts towards finding practical
      ways to reflect upon both the intended and unintended effects of this work. To
      explore what lessons can be learned from the peacebuilding field, this study
      examines the evaluations of Search for Common Ground, a peacebuilding
      organisation working in over 35 countries across the world. Analysis focuses on
      96 evaluations completed between 2013 and 2016 in 24 countries across Africa,
      Asia, and the MENA regions that found unintended effects. Programmes focusing on
      women, youth, and radio were most effective at identifying and explaining
      unintended effects, likely because the project design guided broader lines of
      questioning from the beginning. The paper argues that OECD-DAC guidelines are not
      enough on their own to guide evaluators into exploration of unintended effects,
      and teams instead need to work together to decide where, when and how they will
      look for them. Different approaches were also used to capture positive and
      negative outcomes, suggesting that evaluators need to decide at what level they
      are evaluating and how to tie effects back to the project's contribution. This
      study explores evaluation techniques and approaches used to understand impact in
      complex contexts in the peacebuilding field, and draws on lessons learned for the
      benefit of other fields dealing with similar complexities in international
      development and cooperation among actors.

PMID- 29050644
TI  - Rohingya in Bangladesh: an unfolding public health emergency.

PMID- 29050645
TI  - A global coalition for the fight against heart disease and stroke.

PMID- 29050646
TI  - Worldwide incidence and prevalence of inflammatory bowel disease in the 21st
      century: a systematic review of population-based studies.
AB  - BACKGROUND: Inflammatory bowel disease is a global disease in the 21st century.
      We aimed to assess the changing incidence and prevalence of inflammatory bowel
      disease around the world. METHODS: We searched MEDLINE and Embase up to and
      including Dec 31, 2016, to identify observational, population-based studies
      reporting the incidence or prevalence of Crohn's disease or ulcerative colitis
      from 1990 or later. A study was regarded as population-based if it involved all
      residents within a specific area and the patients were representative of that
      area. To be included in the systematic review, ulcerative colitis and Crohn's
      disease needed to be reported separately. Studies that did not report original
      data and studies that reported only the incidence or prevalence of paediatric
      onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We
      created choropleth maps for the incidence (119 studies) and prevalence (69
      studies) of Crohn's disease and ulcerative colitis. We used temporal trend
      analyses to report changes as an annual percentage change (APC) with 95% CI.
      FINDINGS: We identified 147 studies that were eligible for final inclusion in the
      systematic review, including 119 studies of incidence and 69 studies of
      prevalence. The highest reported prevalence values were in Europe (ulcerative
      colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany)
      and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease
      319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded
      0.3% in North America, Oceania, and many countries in Europe. Overall, 16 (72.7%)
      of 22 studies on Crohn's disease and 15 (83.3%) of 18 studies on ulcerative
      colitis reported stable or decreasing incidence of inflammatory bowel disease in
      North America and Europe. Since 1990, incidence has been rising in newly
      industrialised countries in Africa, Asia, and South America, including Brazil
      (APC for Crohn's disease +11.1% [95% CI 4.8-17.8] and APC for ulcerative colitis
      +14.9% [10.4-19.6]) and Taiwan (APC for Crohn's disease +4.0% [1.0-7.1] and APC
      for ulcerative colitis +4.8% [1.8-8.0]). INTERPRETATION: At the turn of the 21st
      century, inflammatory bowel disease has become a global disease with accelerating
      incidence in newly industrialised countries whose societies have become more
      westernised. Although incidence is stabilising in western countries, burden
      remains high as prevalence surpasses 0.3%. These data highlight the need for
      research into prevention of inflammatory bowel disease and innovations in health
      care systems to manage this complex and costly disease. FUNDING: None.

PMID- 29050647
TI  - Rapid changes in epidemiology of inflammatory bowel disease.

PMID- 29050648
TI  - Diagnosis of deep-vein thrombosis.
AB  - The diagnostic approach to suspected symptomatic deep-vein thrombosis of the
      lower extremities is usually based on non-invasive methods, including the
      estimation of clinical probability, the measurement of D-dimer levels, and
      ultrasonography. The present review discusses the evidence available from the
      literature about the management of the first episode of suspected deep-vein
      thrombosis.

PMID- 29050649
TI  - Obesity status influences the relationship among serum osteocalcin, iron stores
      and insulin sensitivity.
AB  - BACKGROUND & AIMS: Increased iron stores significantly influence the clinical
      course of several chronic metabolic diseases. Recent studies have shown that iron
      overload decreases osteocalcin. We aimed to explore the relationship among
      osteocalcin, iron stores and insulin sensitivity. METHODS: Extensive clinical and
      laboratory measurements, including serum ferritin, cross-linked C-telopeptide of
      type I collagen (CTX) and osteocalcin (OC) concentrations, were analyzed in 250
      adult consecutive Caucasian men. Insulin sensitivity was evaluated through
      frequently sampled intravenous glucose tolerance tests with minimal model
      analysis. RESULTS: Circulating serum ferritin were negatively associated with
      serum OC and CTX (p = 0.004 and p = 0.045 respectively). In all subjects as a
      whole, BMI and ferritin contributed to explain 5.2% of OC variance after
      controlling for age and smoking status. However, the association between OC and
      insulin sensitivity remained significant only in lean subjects (BMI < 25 kg/m2, r
      = 0.468; p = 0.006) whereas the link between serum ferritin concentration and OC
      and CTX were significant only in overweight/obese subjects (BMI >= 25 kg/m2, r = 
      0.229; p = 0.002 and r = -0.196; p = 0.008, respectively). CONCLUSIONS: The
      association of circulating osteocalcin with parameters of insulin sensitivity and
      iron stores were dependent on obesity status. Increased iron stores could
      contribute to the detrimental metabolic effects of overweight and obesity on
      bone.

PMID- 29050650
TI  - Glycaemic response after intake of a high energy, high protein, diabetes-specific
      formula in older malnourished or at risk of malnutrition type 2 diabetes
      patients.
AB  - BACKGROUND & AIMS: Several studies with diabetes-specific formulas (DSFs) for
      hyperglycaemic patients in need of nutritional support have been conducted in non
      malnourished patients, mainly comparing products with varying macronutrient
      compositions. Here, the effect of a high energy, high protein DSF on postprandial
      responses was compared to a product with a similar macronutrient composition in
      malnourished or at risk of malnutrition patients with type 2 diabetes. METHODS:
      In this randomised, double-blind cross-over study, 20 patients were included.
      After overnight fasting, patients consumed 200 mL of a DSF or standard supplement
      (control) (19.6 g protein, 31.2 g carbohydrates and 10.6 g fat), while continuing
      their anti-diabetic medication. The formulas differed in type of carbohydrates
      and presence of fibre. The postprandial glucose, insulin and glucagon responses
      were monitored over 4 h. Data were analysed with a Linear Mixed Model, and
      results of the modified ITT population (n = 19) are shown. RESULTS: Postprandial
      glucose response as incremental area under the curve (iAUC), was lower after
      consumption of DSF compared with control (489.7 +/- 268.5 (mean +/- SD) vs 581.3
      +/- 273.9 mmol/L min, respectively; p = 0.008). Also, the incremental maximum
      concentration of glucose (iCmax) was lower for DSF vs control (3.5 +/- 1.4 vs 4.0
      +/- 1.4 mmol/L; p = 0.007). Postprandial insulin and glucagon levels, expressed
      as iAUC or iCmax, were not significantly different between groups. CONCLUSIONS:
      Consumption of a high energy, high protein DSF by older malnourished or at risk
      of malnutrition type 2 diabetes patients resulted in a significantly lower
      glucose response compared to control. These data suggest that the use of a DSF is
      preferred for patients with diabetes in need of nutritional support.

PMID- 29050651
TI  - [Movement disorders: An update].
AB  - Movement disorders (tremor, chorea, dystonia, tics, and myoclonus) are related to
      basal ganglia and/or interconnected brain areas dysfunction. Clinical examination
      is a key point in order to characterize the abnormal movement and identify
      associated signs that can guide etiological approach. Iatrogenic diseases will be
      systematically ruled out before conducting additional investigations (brain MRI,
      electrophysiological studies). Wilson disease, but also other treatable metabolic
      and/or genetic diseases, and auto-immune diseases will be systematically
      considered. Therapeutic management is symptomatic and based on specific oral
      drugs appropriate to each movement disorders. In some cases, radiosurgery and
      deep brain stimulation should be helpful, especially for tremor and generalized
      dystonia.

PMID- 29050652
TI  - GM(1,N) method for the prediction of anaerobic digestion system and sensitivity
      analysis of influential factors.
AB  - Anaerobic digestion process has been recognized as a promising way for waste
      treatment and energy recovery in a sustainable way. Modelling of anaerobic
      digestion system is significantly important for effectively and accurately
      controlling, adjusting, and predicting the system for higher methane yield. The
      GM(1,N) approach which does not need the mechanism or a large number of samples
      was employed to model the anaerobic digestion system to predict methane yield. In
      order to illustrate the proposed model, an illustrative case about anaerobic
      digestion of municipal solid waste for methane yield was studied, and the results
      demonstrate that GM(1,N) model can effectively simulate anaerobic digestion
      system at the cases of poor information with less computational expense.

PMID- 29050653
TI  - Policy Impact of Research Findings on the Association of Diaper Need and Mental
      Health.
AB  - BACKGROUND: Maternal mental illness constitutes one of most significant public
      health problems facing women of reproductive age and their children. Women who
      mother in poverty experience additional stressors, pointing to the need for
      innovative public health promotion efforts to reduce mental illness. Simple
      innovations, like making diapers more available and affordable, may represent an
      effective method of addressing this problem. This paper describes the research
      findings on diaper need reported by the New Haven Mental Health Outreach for
      Mothers Partnership and the process of translating these findings into broader
      policy and advocacy efforts. METHODS: National-, state-, and local-level diaper
      policy activities that occurred from 2013 to 2016 were examined after a journal
      article that focused on diaper need and associated psychosocial variables was
      published in Pediatrics. RESULTS: Based on analysis of policy activities that
      occurred from 2013 to 2016 after Pediatrics published the diaper need findings,
      several diaper-related policy activities were identified: 1 at the city level, 11
      at the state level, and 2 at the federal level. Five of the identified activities
      represented policy changes that were enacted or implemented. CONCLUSIONS:
      Community coalitions can effect gender-responsive policy change by conducting and
      disseminating research, engaging stakeholders, and mobilizing and leveraging
      their networks.

PMID- 29050654
TI  - Viewing Health Policy through a Gender Lens: Highlights from Several U.S.
      Communities.

PMID- 29050655
TI  - Healthy by Design: Using a Gender Focus to Influence Complete Streets Policy.
AB  - BACKGROUND: Public health leaders in Yellowstone County, Montana, formed an
      alliance to address community-wide issues. One such issue is Complete Streets,
      with its vision of safe streets for all. This case study focuses on development
      and adoption of a Complete Streets policy. It examines how a community coalition,
      Healthy By Design, infused a gender focus into the policymaking process. METHODS:
      An incremental and nonlinear policymaking process was aided by a focus on gender
      and health equity. The focus on a large constituency helped to frame advocacy in
      terms of a broad population's needs, not just special interests. RESULTS: The
      city council unanimously adopted a Complete Streets resolution, informed by a
      gender lens. Healthy By Design further used gender information to successfully
      mobilize the community in response to threats of repeal of the policy, and then
      influenced the adoption of a revised policy. CONCLUSIONS: Policies developed with
      a focus on equity, including gender equity, may have broader impact on the
      community. Such policies may pave the way for future policies that seek to
      transform gender norms toward building a healthier community for all residents.

PMID- 29050656
TI  - Promoting Policy Development through Community Participatory Approaches to Health
      Promotion: The Philadelphia Ujima Experience.
AB  - BACKGROUND: The Philadelphia Ujima Coalition for a Healthier Community
      (Philadelphia Ujima) promotes health improvement of girls, women, and their
      families using a gender framework and community-based participatory research
      approach to addressing gender-based disparities. Institutional policies developed
      through community-based participatory research approaches are integral to
      sustaining gender-integrated health-promotion programs and necessary for reducing
      gender health inequities. This paper describes the results of a policy analysis
      of the Philadelphia Ujima coalition partner sites and highlights two case
      studies. METHODS: The policy analysis used a document review and key informant
      interview transcripts to explore 1) processes that community, faith, and academic
      organizations engaged in a community participatory process used to develop
      policies or institutional changes, 2) types of policy changes developed, and 3)
      initial outcomes and impact of the policy changes on the target population.
      RESULTS: Fifteen policies were developed as a result of the funding from the U.S.
      Department of Health and Human Services Office on Women's Health. Policy changes
      included 1) healthy food options guidance, 2) leadership training on sexual and
      relationship violence, and 3) curricula and programming inclusion and expansion
      of a sex and gender focus in high school and medical school. CONCLUSIONS:
      Organizational practice changes and policies can be activated through individual
      level interventions using a community participatory approach. This approach
      empowers communities to play an integral role in creating health-promoting
      policies.

PMID- 29050657
TI  - B'More Fit for Healthy Babies: Using Trauma-Informed Care Policies to Improve
      Maternal Health in Baltimore City.
AB  - BACKGROUND: Pregnant obese women have an increased risk for infant mortality and
      poor maternal outcomes. Environmental and social conditions pose barriers for
      less-advantaged overweight women to participate in weight loss interventions. The
      B'more Fit for Healthy Babies Program aimed to address existing gender inequities
      that persist where exposure to community-level trauma is present. METHODS: A
      gender-based analysis using qualitative and quantitative approaches informed
      B'more Fit's intervention and identified opportunities for trauma-informed care
      policies. Key data sources for analyses included two series of focus groups and a
      quantitative survey. Review of additional Baltimore-based literature and research
      also informed policy development. RESULTS: A workgroup formulated policies for
      B'more Fit staff and participants. Policies involved technical assistance, staff
      consultation, and gender-sensitive counseling sessions. These activities gained
      the attention of the Baltimore City Health Department's leadership, and
      department-wide trainings were conducted. Highly publicized violence in Baltimore
      led to expanded trauma-informed care training and policy development in all local
      government agencies through a partnership between the Baltimore City Health
      Department and Behavioral Health Systems Baltimore, Inc. CONCLUSIONS: The
      development and monitoring of trauma-informed interventions and policies within
      governmental and human service agencies can counterbalance social and
      environmental exposures. Applying a gender-based and trauma-informed program
      provided B'more Fit participants with strategies for weight loss, improved
      nutrition, and better parenting. Coordinated policies and interventions are
      underway in city institutions to address residents' behavioral health needs and
      improve citywide services.

PMID- 29050658
TI  - Addressing Health Disparities from Within the Community: Community-Based
      Participatory Research and Community Health Worker Policy Initiatives Using a
      Gender-Based Approach.
AB  - BACKGROUND: The Coalition for a Healthier Community for Utah Women and Girls (CHC
      UWAG) focused on addressing obesity-related health disparities impacting Utah
      women of color using community-based participatory research, a gender-based
      approach, and culturally sensitive health promotion activities delivered through
      community health workers (CHWs). A randomized trial of low vs. high intensity
      wellness coaching by CHWs was initiated. During this process, numerous policy
      issues emerged and were tracked. We present a case study illustrating how we
      identified, tracked, and engaged with emerging policy initiatives. METHODS:
      Between September 2011 and August 2017, policy initiatives addressing obesity
      related disparities among Utah women and girls were identified, tracked in a
      shared document, and updated regularly. Policies were classified by level
      (organizational, local, and statewide) and by focus (healthy eating, active
      living, and promotion of community health workers). CHC-UWAG engagement with
      policy work was also documented and tracked. RESULTS: Broad dissemination of
      study findings generated interest in the role of CHWs in addressing obesity.
      Partnering community-based organizations implemented policies focused on healthy
      eating and physical activity. Barriers to the broader use of CHWs in Utah were
      addressed in policy initiatives including the formation of a Utah Public Health
      Association Section for CHWs and a statewide CHW Coalition with involvement of
      CHC-UWAG members. CONCLUSIONS: The regular solicitation of information about
      policy initiatives resulted in successful policy tracking and engagement in
      policy work. The utilization of a gender-based approach helped illuminate the
      impact of emerging policies on the health of women and girls.

PMID- 29050659
TI  - Community Coalitions' Gender-Aware Policy and Systems Changes to Improve the
      Health of Women and Girls.
AB  - BACKGROUND: Addressing environmental barriers and community conditions through
      policy and systems change provides the foundation for creating sustainable public
      health change at the population level. In an effort to influence population-level
      change that is gender aware, the United States Department of Health and Human
      Services Office on Women's Health funded the Coalition for a Healthier Community
      initiative supporting 10 grantees in the implementation of gender-based, public
      health systems approaches to improve women and girls' health. METHODS: A national
      evaluation assessed the extent to which these gender-aware public health systems
      approaches result in programs and policies that are sustainable and cost
      effective in addressing health disparities in women and girls. For this paper, a
      review of policies reported on in grantees' quarterly progress reports was
      conducted, and policies were categorized based on each policy's status, level,
      sector affected, and whether it was gender aware. RESULTS: The review revealed 77
      policies at varying stages of development or implementation intended to
      facilitate systems-level change at the coalition, school, organizational, local,
      or state level. Fifty-one percent of these policies were identified as being
      gender aware, because they were intended to reduce barriers to or increase
      facilitators of gender equity. CONCLUSIONS: Community coalitions, like the
      Coalition for a Healthier Community coalitions, can be valuable channels for
      promoting policy change, as demonstrated by the many policies developed and/or
      supported by the Coalition for a Healthier Community grantees in their attempt to
      meet the needs of women and girls.

PMID- 29050660
TI  - The Fortuitous Discovery of the Olin EILOBI Breathing Techniques: A Case Study.
AB  - Exercise-induced laryngeal obstruction (EILO) is the term for the condition
      previously named vocal cord dysfunction and paradoxical vocal fold motion. It is
      defined by glottic or supraglottic obstruction during periods of intense
      exercise. Not all patients respond to conventional therapy with speech-language
      pathology, behavioral health interventions, and treatment of contributing
      conditions. In this edition of Journal of Voice, the authors describe a novel
      series of respiratory retraining techniques, now called Olin EILOBI (EILO
      biphasic inspiratory) breathing techniques, specifically designed for athletes
      with EILO. This case presentation describes the discovery of one of these
      techniques during a session of therapeutic laryngoscopy during exercise. The
      patient was an adolescent with EILO who demonstrated a positive response to
      therapy with a variant of these techniques over a few days, having previously
      struggled with symptoms despite multiple sessions of conventional respiratory
      retraining over the course of months.

PMID- 29050661
TI  - The Olin EILOBI Breathing Techniques: Description and Initial Case Series of
      Novel Respiratory Retraining Strategies for Athletes with Exercise-Induced
      Laryngeal Obstruction.
AB  - INTRODUCTION: Exercise-induced laryngeal obstruction (EILO), the condition
      previously known as paradoxical vocal fold motion and vocal cord dysfunction, is
      characterized by inappropriate glottic or supraglottic obstruction during high
      intensity exercise, causing exertional dyspnea, frequently with stridor. EILO is
      definitively diagnosed through upper-airway visualization during a characteristic
      episode. Although respiratory retraining is a primary therapy for EILO, many
      patients report symptom persistence despite adequate performance of traditional
      techniques. This report describes three novel breathing techniques for EILO, the
      Olin EILOBI (EILO biphasic inspiratory) breathing techniques. We include a
      teaching process and case series with patient-reported assessments. MATERIALS AND
      METHODS: Following descriptions of the techniques and teaching process, we
      present data from a questionnaire offered to all patients who learned at least
      one of the techniques between September 2015 and March 2017. Subjects evaluated
      (1) expectation setting, (2) teaching processes, (3) their ability to implement
      the techniques during high-intensity exercise, and (4) perceived clinical
      effectiveness. RESULTS: Ninety-five percent of eligible patients participated, a
      primarily young, female, and Caucasian sample. Over 50% of subjects competed at
      the high school varsity level. Sixty-two percent of subjects perceived reasonable
      expectations, and 82% positively evaluated the teaching process. Seventy-nine
      percent were able to employ their technique in the high-intensity activity of
      choice, and 66% perceived clinical effectiveness with the techniques.
      CONCLUSIONS: The Olin EILOBI breathing techniques are novel respiratory
      retraining techniques for use in high-intensity exercise. Case series subjects
      reported reasonable expectations, a helpful teaching process, the ability to use
      these techniques during high-intensity exercise, and perceived clinical
      effectiveness.

PMID- 29050662
TI  - Keratometry - A technique that should be relegated to the clinical dark ages?

PMID- 29050663
TI  - Vitamin D-deficiency induces eosinophil spontaneous activation.
AB  - Eosinophils (Eo) play a critical role in immunity and immune inflammation. The
      maintenance of Eo homeostasis is not fully understood yet. Vitamin D (VitD) is
      involved in the regulation of a large number of biochemical reactions. This study
      tests a hypothesis that VitD receptor (VDR) contributes to the homeostasis of
      Eos. In this study, EoL-1 cells (an Eo cell line) were cultured in the presence
      or absence of calcitriol. The Eo-mediators, including major basic protein (MBP),
      Eo peroxidase (EPX), Eo cationic protein (ECP) and Eo-derived neurotoxin (EDN),
      were assessed in the culture supernatant and in EoL-1 cells. We observed that, in
      a VitD deficient environment, EoL-1 cells produced high levels of the Eo
      mediators, including MBP, EPX, ECP and EDN, which could be suppressed by the
      addition of calcitriol to the culture. EoL-1 cells expressed VitD receptor (VDR),
      which was up regulated by exposure to calcitriol. VDR formed complexes with the
      transcription factors of the Eo-mediators, which prevented the transcription
      factors to bind to the promoters of the Eo-mediators, and therefore prevented the
      Eo-mediated gene transcription. The Eo spontaneous activation was also found in
      the intestinal mucosa of VDR-deficient mice, in which the intestinal epithelial
      barrier dysfunction was observed. In conclusion, VDR contributes to the
      maintenance of the homeostasis of Eos by regulating the gene transcription of the
      Eo mediators. The VDR-deficiency is one of the causative factors inducing Eo
      spontaneous activation. This phenomenon may be taken into account in the
      management of the Eo-related diseases.

PMID- 29050664
TI  - Sodium Chloride Does Not Ensure Microbiological Safety of Foods: Cases and
      Solutions.
AB  - Addition of salt or salt-containing water to food is one of the oldest and most
      effective preservation methods in history; indeed, salt-cured foods are generally
      recognized as microbiologically safe due to their high salinity. However, a
      number of microbiological risks remain. The microbiological hazards and risks
      associated with salt-cured foods must be addressed more in-depth as they are
      likely to be underestimated by previous studies. This review examined a number of
      scientific reports and articles about the microbiological safety of salt-cured
      foods, which included salted, brined, pickled, and/or marinated vegetables, meat,
      and seafood. The following subjects are covered in order: (1) clinical cases and
      outbreaks attributed to salt-cured foods; (2) the prevalence of foodborne
      pathogens in such foods; (3) the molecular, physiological, and virulent responses
      of the pathogens to the presence of NaCl in both laboratory media and food
      matrices; (4) the survival and fate of microorganisms in salt-cured foods (in the
      presence/absence of additional processes); and (5) the interaction between NaCl
      and other stressors in food processes (e.g., acidification, antimicrobials,
      drying, and heating). The review provides a comprehensive overview of potentially
      hazardous pathogens associated with salt-cured foods and suggests further
      research into effective intervention techniques that will reduce their levels in
      the food chain.

PMID- 29050665
TI  - Uranium Bioreduction and Biomineralization.
AB  - Following the development of nuclear science and technology, uranium
      contamination has been an ever increasing concern worldwide because of its
      potential for migration from the waste repositories and long-term contaminated
      environments. Physical and chemical techniques for uranium pollution are
      expensive and challenging. An alternative to these technologies is microbially
      mediated uranium bioremediation in contaminated water and soil environments due
      to its reduced cost and environmental friendliness. To date, four basic
      mechanisms of uranium bioremediation-uranium bioreduction, biosorption,
      biomineralization, and bioaccumulation-have been established, of which uranium
      bioreduction and biomineralization have been studied extensively. The objective
      of this review is to provide an understanding of recent developments in these two
      fields in relation to relevant microorganisms, mechanisms, influential factors,
      and obstacles.

PMID- 29050666
TI  - The Contribution of Bacteriophages to the Biology and Virulence of Pathogenic
      Clostridia.
AB  - Bacteriophages are key players in the evolution of most bacteria. Temperate
      phages have been associated with virulence of some of the deadliest pathogenic
      bacteria. Among the most notorious cases, the genes encoding the botulinum
      neurotoxin produced by Clostridium botulinum types C and D and the alpha-toxin
      (TcnA) produced by Clostridium novyi are both encoded within prophage genomes.
      Clostridium difficile is another important human pathogen and the recent
      identification of a complete binary toxin locus (CdtLoc) carried on a C.
      difficile prophage raises the potential for horizontal transfer of toxin genes by
      mobile genetic elements. Although the TcdA and TcdB toxins produced by C.
      difficile have never been found outside the pathogenicity locus (PaLoc), some
      prophages can still influence their production. Prophages can alter the
      expression of several metabolic and regulatory genes in C. difficile, as well as
      cell surface proteins such as CwpV, which confers phage resistance. Homologs of
      an Agr-like quorum sensing system have been identified in a C. difficile
      prophage, suggesting that it could possibly participate in cell-cell
      communication. Yet, other C. difficile prophages contain riboswitches predicted
      to recognize the secondary messenger molecule c-di-GMP involved in bacterial
      multicellular behaviors. Altogether, recent findings on clostridial phages
      underline the diversity of mechanisms and intricate relationship linking phages
      with their host. Here, milestone discoveries linking phages and virulence of some
      of the most pathogenic clostridial species will be retraced, with a focus on C.
      botulinum, C. novyi, C. difficile, and Clostridium perfringens phages, for which
      evidences are mostly available.

PMID- 29050667
TI  - Toward Genome-Based Metabolic Engineering in Bacteria.
AB  - Prokaryotes modified stably on the genome are of great importance for production
      of fine and commodity chemicals. Traditional methods for genome engineering have
      long suffered from imprecision and low efficiencies, making construction of
      suitable high-producer strains laborious. Here, we review the recent advances in
      discovery and refinement of molecular precision engineering tools for genome
      based metabolic engineering in bacteria for chemical production, with focus on
      the lambda-Red recombineering and the clustered regularly interspaced short
      palindromic repeats/Cas9 nuclease systems. In conjunction, they enable the
      integration of in vitro-synthesized DNA segments into specified locations on the
      chromosome and allow for enrichment of rare mutants by elimination of unmodified
      wild-type cells. Combination with concurrently developing improvements in
      important accessory technologies such as DNA synthesis, high-throughput screening
      methods, regulatory element design, and metabolic pathway optimization tools has
      resulted in novel efficient microbial producer strains and given access to new
      metabolic products. These new tools have made and will likely continue to make a
      big impact on the bioengineering strategies that transform the chemical industry.

PMID- 29050668
TI  - Microbial Transformation of Iodine: From Radioisotopes to Iodine Deficiency.
AB  - Iodine is a biophilic element that is important for human health, both as an
      essential component of several thyroid hormones and, on the other hand, as a
      potential carcinogen in the form of radioiodine generated by anthropogenic
      nuclear activity. Iodine exists in multiple oxidation states (-1, 0, +1, +3, +5,
      and +7), primarily as molecular iodine (I2), iodide (I-), iodate [Formula: see
      text] , or organic iodine (org-I). The mobility of iodine in the environment is
      dependent on its speciation and a series of redox, complexation, sorption,
      precipitation, and microbial reactions. Over the last 15years, there have been
      significant advances in iodine biogeochemistry, largely spurred by renewed
      interest in the fate of radioiodine in the environment. We review the
      biogeochemistry of iodine, with particular emphasis on the microbial processes
      responsible for volatilization, accumulation, oxidation, and reduction of iodine,
      as well as the exciting technological potential of these fascinating
      microorganisms and enzymes.

PMID- 29050669
TI  - "Transfusion Clinique et Biologique" - what makes transfusion medicine and
      biology so special?

PMID- 29050670
TI  - Ginseng polysaccharide serves as a potential radiosensitizer through inducing
      apoptosis and autophagy in the treatment of osteosarcoma.
AB  - Recent studies have confirmed that the combined use of anti-cancer drugs with
      ionizing radiation (IR) could improve the sensitivity of osteosarcoma (OS) cells.
      Therefore, it is necessary to identify potential effective drugs for the
      enhancement of IR-radiosensitivity. In the current study, we found that 20, 10,
      5, and 1 MUM of ginseng polysaccharide (GPS) significantly suppressed MG-63 cell
      viability with or without gamma-ray radiation in a dose- and time-dependent
      manner. Strikingly, 20 MUM of GPS combined with 5 Gy treatment suppressed colony
      formation capacity by nearly 13.75~fold compared with IR treatment alone. Our
      results showed that GPS could markedly induce early apoptosis and autophagy in MG
      63 cells. A higher drug concentration and a greater exposure dose were directly
      associated with more apoptosis and autophagy in cells. Western blot analysis
      showed that GPS decreased the phosphorylation of p38 and AKT as well as the
      protein expression of Bax and cleaved-caspase3. In summary, GPS inhibited
      proliferation and increased apoptosis and autophagic death in OS cells,
      indicating that GPS may be a potential effective auxiliary drug for improving the
      IR sensitivity of OS patients.

PMID- 29050672
TI  - Genetic diversity of multidrug-resistant Mycobacterium tuberculosis strains
      isolated from tuberculosis patients in Iran using MIRU-VNTR technique.
AB  - Tuberculosis (TB) is considered as one of the most important infectious diseases
      in the world, and recent rise and spread of multidrug-resistant (MDR)
      Mycobacterium tuberculosis (MTB) strains, have made the matter worsened. Due to
      the importance of TB prevalence in Iran, this study was designed to investigate
      the genetic diversity among MDR strains of MTB by MIRU-VNTR typing scheme. A
      total of 88 drug resistant M. tuberculosis isolates belong to pulmonary TB cases
      were collected from several TB reference centers of Iran. Drug susceptibility
      testing for Isoniazid and Rifampin was performed using the agar proportion method
      and MDR isolates were underwent genotyping by using 12-locus- based MIRU-VNTR
      typing. On performing proportion method, 22 isolates were identified as MDR. By
      typing of MDR isolates using 12-loci MIRU-VNTR technique, high diversity were
      demonstrated in MDR strains and these were classified into 20 distinct MIRU-VNTR
      genotypes. MIRU loci 10 and 26 were the most discriminatory loci with 8 and 7
      alleles respectively; while MIRU loci 2, 20, 24 and 39 were found to be the least
      discriminatory with 1-2 alleles each. We noticed a mixed infection in isolate 53,
      as this isolate comprised simultaneous two alleles in MIRU loci 40, 10, 16 and
      39. In conclusion, this result represents MIRU-VNTR typing as a useful tool for
      studying genetic diversity of MDR-MTB in regional settings, and will help the
      health sectors to construct a preventive program for MDR-TB. Additionally, it can
      detect mixed infection which can facilitate management of treatment.

PMID- 29050671
TI  - Gambogic acid improves non-small cell lung cancer progression by inhibition of
      mTOR signaling pathway.
AB  - Gambogic acid (GA) has been shown to inhibit cancer cell proliferation, induce
      apoptosis, and enhance reactive oxygen species accumulation. However, whether GA
      could improve multidrug resistance through modulating autophagy has never been
      explored. We demonstrated that the combination of GA and cisplatin (CDDP)
      resulted in a stronger growth inhibition effect on A549 and NCI-H460 cells using
      the MTT assay. Furthermore, treatment with GA significantly increased autophagy
      in these cells. More importantly, GA-induced cell death could be largely
      abolished by 3-methyladenine (3-MA) or chloroquine (CQ) treatment, suggesting
      that GA-induced cell death was dependent on autophagy. Western blot analysis
      showed that GA treatment suppressed the activation of Akt, mTOR, and S6. In
      addition, using a GA and rapamycin combination induced more cell death compared
      to either GA or rapamycin alone. In summary, GA may have utility as an adjunct
      therapy for non-small cell lung cancer (NSCLC) patients through autophagy
      dependent cell death, even when cancer cells have developed resistance to
      apoptosis.

PMID- 29050673
TI  - The relationship between the CYP19 alleles rs727479A/C, rs700518A/G, and
      rs700519C/T and pregnancy outcome after assisted reproductive technology in
      patients with polycystic ovary syndrome in a Chinese population: A population
      based study.
AB  - This study investigated the relationship between the CYP19 alleles, rs727479A/C,
      rs700518A/G, and rs700519C/T, and pregnancy outcome after assisted reproductive
      technology (ART) in patients with polycystic ovary syndrome (PCOS). Between
      January 2012 and September 2015, 293 PCOS patients undergoing ART were randomly
      selected for the study. According to pregnancy outcome after ART, the patients
      were assigned to pregnancy and non-pregnancy groups. CYP19 rs727479A/C,
      rs700518A/G and rs700519C/T genotypes were determined using the denaturing high
      performance liquid chromatography (DHPLC) method. Haplotype frequencies of the
      CYP19 alleles rs727479A/C, rs700518A/G and rs700519C/T were estimated using the
      SHEsis platform. Logistic regression analysis was employed to analyze the factors
      influencing the pregnancy outcome after ART. The frequency of the AC + CC
      genotype of rs727479A/C was higher in the pregnancy group than in the non
      pregnancy group. The frequency of the CT + TT genotype of rs700519A/G was also
      higher in the pregnancy group than in the non-pregnancy group. Haplotype analysis
      indicated that the AAC and AGT haplotypes both exhibited unfavorable influence on
      the pregnancy outcome after ART. The AAT and CGT haplotypes were favorable to the
      pregnancy outcome after ART. Logistic regression analysis suggested that the
      rs727479A/C AA genotype, the rs700519C/T CC genotype and body mass index (BMI)
      might exert unfavorable influence on the pregnancy outcome after ART for PCOS
      patients. These findings indicated that the CYP19 alleles rs727479A/C and
      rs700519C/T might be associated with the pregnancy outcome after ART in patients
      with PCOS.

PMID- 29050675
TI  - Comparison of serum acetyl hydrolase (PAF-AH) and paraoxonase 1 (PON1) values
      between prostate cancer patients and a control group.
AB  - The aim of the study was to measure platelet-activating factor acetyl hydrolase
      (PAF-AH) and paraoxonase (PON1) enzyme activity levels in patients with high Psa
      values to compare with healthy peers and also to determine the efficacy of these
      parameters in predicting pathologic results of patients with high Psa values.
      This study included 66 patients with Psa value > 4 ng/dl (Group 1) and 44
      patients with Psa <4 ng/dl (Group 2) for a total of 110 patients. Parameters
      measured in serum of PON1, PAF-AH, and MDA were compared between the groups.
      Additionally the same parameters were compared between patients with prostate
      biopsy performed due to high Psa and diagnosed with cancer and the control group
      with normal Psa values. The PAF-AH activity in Group 1 was 125.17 +/- 8.64 and in
      Group 2 was 120.08 +/- 9.23 U/ml (p = 0.003). The PON1 activity was 63.12 +/-
      6.74 and 65.91 +/- 7.77 U/ml in the groups, respectively (p = 0.04).
      Additionally, there were significant differences identified between the control
      group and PCa diagnosis group in terms of PAF-AH and PON1 activities (p = 0.004
      and p = 0.02, respectively). The enzyme activity of PAF-AH and PON1 measured in
      serum of patients with high Psa value and patients with diagnosis of prostate
      cancer (PCa) were identified to have changed by a significant amount compared to
      healthy peers with normal Psa value. It was concluded that these parameters may
      be beneficial markers for use in assessment of patients with high Psa value.

PMID- 29050674
TI  - The outcomes of glucose abnormalities in chronic hepatitis C patients receiving
      interferon-free direct antiviral agents.
AB  - Direct-acting antiviral agents (DAAs) have been widely used for chronic hepatitis
      C (CHC) treatment recently. The characteristics of glucose abnormalities after
      DAAs therapy however, remain elusive. We aimed to elucidate the mutual impact
      between treatment response and parameters of glucose abnormalities after DAAs
      therapy in CHC patients. CHC patients who received DAAs therapy were recruited.
      The primary outcome measurements were their insulin resistance (IR) and beta-cell
      function assessed by the homeostasis model assessment (HOMA) method before
      treatment and at end-of-follow-up (EOF). Sixty-five CHC patients (19 males, mean
      age = 59.8 +/- 10.3 years) were consecutively enrolled. They included 47 (72.3%)
      patients of genotype-1 infection. The treatment regimens among patients were
      sofosbuvir in 30 patients, paritaprevir-ritonavir/ombitasvir/dasabuvir in 23
      patients, and asunaprevir/daclatasvir in 12 patients respectively. The overall
      sustained virological response rate was 98.5%. The mean IR at EOF was 2.6 +/-
      1.8, which was not significantly different from baseline level (2.7 +/- 2.9, P =
      0.75). There was a significant improvement of beta-cell function at EOF compared
      to baseline (107.7 +/- 86.8 to 86.7 +/- 44.5, P = 0.05). The amelioration of beta
      cell function at EOF was significantly observed among 23 patients of high
      baseline IR (166.7 +/- 111.3 of baseline vs 105.7 +/- 48.2 of EOF, P = 0.04). Six
      (60%) of the 10 pre-diabetic patients at baseline achieved a normoglycemic state
      at EOF. Successful eradication of HCV by DAAs might improve glucose abnormalities
      in CHC patients, particularly among those who had high IR.

PMID- 29050676
TI  - Effects of gripping volume in the mechanical strengths of orthodontic mini
      implant.
AB  - The objective of study was to investigate the correlation between the mechanical
      strengths [insertion torque (IT); resonance frequency (RF); and horizontal
      pullout strength (HPS)] and gripping volume (GV) of mini-implants. Thirty mini
      implants of three types (Type A: 2 mm * 10 mm, cylindrical, titanium alloy; Type
      B: 2 mm * 10 mm, tapered, stainless steel; and Type C: 2 mm * 11 mm, cylindrical,
      titanium alloy) were inserted 7 mm into artificial bones. One-way analysis of
      variance and Spearman's test were applied to assess intergroup comparisons and
      intragroup correlations. The null hypothesis was that no statistically
      significant correlations exist between the GV and mechanical strengths (IT, RF,
      and HPS). In the IT test, Type C (14.2 Ncm) had significantly (p=0.016) greater
      values than did Type A (12.4 Ncm). In the RF analysis, no significant difference
      was observed among the three types of mini-implants. In the HPS test, Type C
      (388.9 Ncm) was significantly larger than both Type B (294.5 Ncm) and Type A (286
      Ncm). In the GV measurement, Type C (14.4 mm3) was significantly larger than Type
      B (11.4 mm3) and Type A (9.2 mm3). Type A and Type B exhibited no significant
      correlations among the tests. Therefore, the null hypothesis was accepted.
      Although no significant correlation was noted between the GV and mechanical
      strengths (IT, RF, and HPS), we observed a trend that the mechanical strengths
      (IT, RF, and HPS) of the mini-implants corresponded to the order and values of GV
      (Type C > Type B > Type A).

PMID- 29050677
TI  - Cost effectiveness of hepatitis C treatments: Need for a comprehensive
      evaluation.

PMID- 29050678
TI  - Reply to "cost effectiveness of hepatitis C treatments: Need for a comprehensive
      evaluation".

PMID- 29050679
TI  - Glycaemic control of elderly patients with type 2 diabetes mellitus in Spain
      (2015) and its relationship with functional capacity and comorbidity. The
      Escadiane study.
AB  - OBJECTIVES: To understand the state of glycaemic control of elderly patients with
      type 2 diabetes mellitus in Spain and its relationship with functional capacity
      and comorbidity. METHODS: Cross-sectional, observational, multicentre national
      study on patients with diabetes mellitus aged 65 years or older. The study
      analysed demographic and anthropometric variables, cardiovascular risk factors,
      clinical and laboratory data, associated comorbidity and treatments. We analysed
      the functional capacity using the Barthel index and the comorbidity with Charlson
      index. RESULTS: The study included 939 patients with a mean age of 76.4+/-6.7
      years. The mean glycated haemoglobin (HbA1c) level was 7.0%+/-1.2%, and the mean
      basal blood glucose level was 137+/-39.6mg/dL. The HbA1c level showed
      statistically significant differences depending on the degree of disability. In
      the patients who were totally, severely, moderately or slightly dependent or who
      were independent, the mean HbA1c levels were 7.0%, 7.9%, 7.4% and 7.0%,
      respectively (P<.028). HbA1c levels were 7.3%, 7.1% and 6.9% in the patients with
      very high, high and medium comorbidity, respectively (P<.001). CONCLUSIONS: Mean
      HbA1c levels in elderly patients with type 2 diabetes analysed in Spain are below
      those recommended by the main clinical practice guidelines. The levels are higher
      in patients who have more functional disability and a higher level of
      comorbidity.

PMID- 29050680
TI  - Reply to "Does prehospital care influence the profile of patients with acute
      cardiac failure?"

PMID- 29050681
TI  - The R-Wave Sign as a Predictor of Ventricular Tachyarrhythmias in Brugada
      Syndrome: The Criteria Need Verification and Clarification.

PMID- 29050682
TI  - Effect of Exceptional Parental Longevity and Lifestyle Factors on Prevalence of
      Cardiovascular Disease in Offspring.
AB  - Offspring of parents with exceptional longevity (OPEL) manifest lower prevalence
      of cardiovascular disease (CVD), but the role of lifestyle factors in this unique
      cohort is not known. Our study tested whether OPEL have lesser prevalence of CVD
      independent of lifestyle factors. Prevalence of CVD and CVD risk factors was
      assessed in a population of community-dwelling Ashkenazi Jewish adults aged 65 to
      94 years. Participants included OPEL (n = 395), defined as having at least 1
      parent living past the age of 95 years, and offspring of parents with usual
      survival (OPUS, n = 450), defined as having neither parent survive to 95 years.
      Medical and lifestyle information was obtained using standardized questionnaires.
      Socioeconomic status was defined based on validated classification scores.
      Dietary intake was evaluated with the Block Brief Food Frequency Questionnaire
      (2000) in a subgroup of the study population (n = 234). Our study found no
      significant differences in the prevalence of obesity, smoking, alcohol use,
      physical activity, social strata scores, and dietary intake between the 2 groups.
      After adjustment for age and gender, the OPEL demonstrated 29% lower odds of
      having hypertension (95% confidence interval [CI] 0.53 to 0.95), 65% lower odds
      of having had a stroke (95% CI 0.14 to 0.88), and 35% lower odds of having CVD
      (95% CI 0.43 to 0.98), compared with OPUS. In conclusion, exceptional parental
      longevity is associated with lower prevalence of CVD independent of lifestyle,
      socioeconomic status, and nutrition, thus highlighting the potential role of
      genetics in disease-free survival among individuals with exceptional parental
      longevity.

PMID- 29050683
TI  - Correlation of Fractional Flow Reserve With Ischemic Burden Measured by
      Cardiovascular Magnetic Resonance Perfusion Imaging.
AB  - Cardiovascular magnetic resonance (CMR) perfusion imaging and fractional flow
      reserve (FFR) assess myocardial ischemia. FFR measures the pressure loss across a
      stenosis determining hemodynamic significance but does not assess the area
      subtended by the stenotic vessel. CMR perfusion imaging measures the extent of
      myocardial blood flow reduction (=ischemic burden). Both techniques allow for
      continuous rather than categorical evaluation, but their relationship is poorly
      understood. This study investigates the relationship between the FFR value and
      the extent of myocardial ischemia. Forty-nine patients with angina underwent CMR
      perfusion imaging. FFR was measured in vessels with a visual diameter stenosis
      >40%. The extent of ischemia for each coronary artery was measured by delineating
      the perfusion defect on the CMR images and expressing as a percentage of the left
      ventricular myocardium. The correlation between the extent of ischemia measured
      by CMR and FFR was good (r = -0.85, p < 0.0005). The mean FFR value was 0.67 +/-
      0.17, and the mean perfusion defect was 8.9 +/- 9.3%. An FFR value of >=0.75 was
      not associated with ischemia on CMR. The maximum amount of ischemia (23.0 +/-
      1.5%) was found at FFR values 0.4 to 0.5. In patients with 1 vessel disease
      (49%), the mean ischemic burden was 15.3 +/- 8.3%. In patients with 2 vessel
      diseases (18%), the mean ischemic burden was 26.0 +/- 12%. Reproducibility for
      the measurement of ischemic burden was very good with a Kappa coefficient (k =
      0.826, p = 0.048). In conclusion, there is good correlation between the FFR value
      and the amount of myocardial ischemia in the subtended myocardium.

PMID- 29050684
TI  - Comparison of Accuracy of One-Use Methods for Calculating Fractional Flow Reserve
      by Intravascular Optical Coherence Tomography to That Determined by the Pressure
      Wire Method.
AB  - Although the identification of the hemodynamic significance of coronary lesions
      becomes important for revascularization strategy, the potential role of 3
      dimensional high-resolution intracoronary optical coherence tomography (OCT) for
      predicting functional significance of coronary lesions remains unclear. We
      assessed the diagnostic performance of 2 computational approaches for deriving
      fractional flow reserve (FFR) from intravascular OCT images. We developed 2
      methods to derive FFR-OCT by AFD (FFR-OCTAFD) and FFR-OCT by CFD (FFR-OCTCFD).
      Among 217 eligible patients between 2011 and 2014, 104 were included for data
      analysis (9 for derivation, 95 for validation). Luminal geometries from 3
      dimensional OCT were used for both FFR-OCTAFD and FFR-OCTCFD calculations. The
      analytical fluid dynamics method calculated FFR from the blood flow resistance
      estimated using Poiseuille's law. For computational fluid dynamics, we
      numerically solved the Navier-Stokes equation in a steady-state flow with the
      distal porous media model for the capillary vessels. We examined the diagnostic
      performance of FFR-OCTAFD and FFR-OCTCFD compared with the pressure-wire measured
      FFR. The accuracy, sensitivity, specificity, PPV, and NPV were 86%, 65%, 94%,
      81%, and 88% for FFR-OCTAFD and 86%, 73%, 91%, 76%, and 90% for FFR-OCTCFD. The
      area under the curve of the receiver-operating characteristic curve was 0.88 for
      FFR-OCTAFD and 0.86 for FFR-OCTCFD. FFR-OCTAFD and FFR-OCTCFD showed a strong
      linear correlation with the measured FFR (r = 0.631; p <0.001, r = 0.655; p
      <0.001, respectively). FFR derived from high-resolution volumetric OCT images
      showed high diagnostic performance for the detection of coronary ischemia. In
      conclusion, OCT-derived FFR may be useful for guiding the management of coronary
      artery disease.

PMID- 29050685
TI  - Renal Function Changes Following Left Ventricular Assist Device Implantation.
AB  - Limited data assessing the clinical significance of post-left ventricular assist
      device (LVAD) in renal function are available. We aimed to investigate the impact
      of changes in renal function after LVAD implantation on subsequent long-term
      outcomes. We followed 184 patients with HeartMate II LVADs implanted between May
      2008 and November 2014. Serial assessment of renal function, was performed at
      baseline and at day 1, day 7, 1 month, 3 months, 6 months, 1 year, and 2 years
      after implantation. Effects of 1-month GFR and changes in GFR from baseline to 1
      month on long-term mortality and hospital re-admission were evaluated. There were
      30 patients with GFR <45 (low), 44 with GFR 45 to 59 (intermediate), and 110 with
      GFR >=60 (normal) at baseline. Only patients with baseline GFR <45 experienced
      significant improvement in GFR after 2 years of follow-up (p = 0.012). At 1
      month, a higher GFR category was significantly associated with a 31% reduction in
      mortality (hazard ratio [HR] 0.69, CI 0.49 to 0.98, p = 0.036), but not re
      admission. Patients with baseline low and intermediate GFR who had no improvement
      in renal function category at 1 month experienced significantly greater risk of
      mortality (HR 1.95, CI 1.10 to 3.43, p = 0.022) and re-admission (HR 1.75, CI
      1.07 to 2.84, p = 0.025), relative to patients whose GFR was normal at baseline
      and 1 month. In conclusion, renal function after LVAD implantation improves in
      patients with GFR <45. Change in renal function from baseline to 1 month after
      implantation is a powerful marker of long-term outcomes.

PMID- 29050686
TI  - Gender Differences in Cardiac Resynchronization Therapy Device Choice and Outcome
      in Patients >=75 Years of Age with Heart Failure.
AB  - Cardiac resynchronization therapy (CRT) is an established therapy for heart
      failure and can be delivered through a CRT pacemaker (CRT-P) or a CRT
      defibrillator (CRT-D). CRT-P devices are smaller and less expensive, have better
      battery longevity, and have been subject to fewer recalls and advisories but
      cannot deliver high-energy shocks to terminate potentially lethal ventricular
      arrhythmias. As published guidelines do not distinguish between CRT-P and CRT-D
      indications, we examined the practice of prescribing these devices in older women
      and men with heart failure. A total of 512 CRT recipients (age >=75 years, 26%
      women, 21% CRT-P) were included in this analysis. Baseline characteristics were
      collected on all patients, and overall survival was compared by gender and type
      of CRT device implanted. Women were more likely to receive CRT-Ps than men (26%
      vs 19%). Men with CRT-Ps were significantly older than women with CRT-Ps and both
      men and women with CRT-Ds (p = 0.04). In addition, women had lower all-cause
      mortality compared with men (hazard ratio [HR] 0.75, confidence interval [CI]
      0.58 to 0.99, p = 0.04), mainly among CRT-P recipients (HR 0.48, CI 0.26 to 0.8,
      p = 0.02), but this association was attenuated after adjusting for differences in
      patient characteristics (HR 0.56, CI 0.26 to 1.18, p = 0.13). In conclusion,
      women are more likely to receive CRT-Ps than men. Whether this difference is
      driven by patient preference or physician biases remains unclear. Women with CRT,
      particularly CRT-Ps, have a better overall survival than men. These differences,
      which may be driven by unbalanced baseline characteristics of patients or by
      differences in gender response to CRT, deserve further investigation.

PMID- 29050687
TI  - Comparison of adverse events and postoperative mobilization following knee
      extensor mechanism rupture repair: A systematic review and network meta-analysis.
AB  - BACKGROUND: Extensor mechanism rupture (EMR) of the knee is a rare but
      potentially debilitating injury that often occurs due to trauma. While a wide
      variety of surgical treatments have been reported, there is currently no
      consensus on the most successful treatment method. The timing of post-operative
      joint mobilization is also critical for successful recovery after EMR repair.
      Despite the traditional method of complete immobilization for 6 weeks, there is
      an increasing trend towards early post-operative knee mobilization. The purpose
      of this network meta-analysis was to compare adverse event rates and function
      outcomes between repair methods and between post-operative mobilization
      protocols. METHODS: MEDLINE, EMBASE, Web of Science, and Cochrane Central
      electronic databases were searched in August 2016 for observational studies
      involving repair of acute, traumatic EMRs. Data extraction included functional
      outcomes, adverse events, and additional surgeries. Cohort studies that were used
      in functional outcome analysis were assessed for risk of bias by the Newcastle
      Ottawa Quality Assessment Scale (NOS). RESULTS: Twenty-three studies (709
      patients) were included for adverse event analysis. There were no significant
      differences in adverse event or additional surgery rates between EMR repair
      methods However, early mobilization produced significantly higher adverse event
      rates (p=0.02) and total event rates (p<0.001) than late mobilization, but the
      difference in additional surgery rates was not significant (p=0.06). Six studies
      (85 patients) were included for functional outcome analysis. There were no
      significant differences in thigh girth atrophy or muscle strength compared to the
      contralateral leg between patients treated with transosseous drill holes and
      simple end-to-end sutures. CONCLUSIONS: We performed the first network meta
      analysis to date comparing treatment of EMRs. Our results support the current
      body of knowledge that there is no single superior repair method. Although there
      is an increasing trend towards early or immediate post-operative knee
      mobilization, we found that early mobilization is associated with significantly
      higher adverse event and total event rates compared to fixed immobilization for a
      minimum of 6 weeks, implicating an increased financial burden and decreased
      quality of life associated with early post-operative mobilization.

PMID- 29050688
TI  - No association between surgical delay and mortality following distal femoral
      fractures. A study from the danish fracture database collaborators.
AB  - BACKGROUND: The purpose of this study was to investigate whether surgical delay
      or the educational level of surgeon is associated with early mortality in
      patients with distal femoral fractures. METHODS: 392 consecutive patients aged
      >=50 years registered in the Danish Fracture Database for surgery of a non
      pathological, closed, low-energy distal femoral fracture (AO33A-C) were included.
      Data included age, gender, American Society of Anaesthesiologists (ASA) score,
      type of fracture, educational level of surgeon and surgical delay. Educational
      level of surgeon was defined as "attending or above as surgeon", "attending or
      above as supervisor" or "below attending alone". Surgical delay was defined as
      hours (h) from radiological diagnostics until onset of surgery. Mortality data
      was provided by The Civil Registration System. Mortality rates were calculated
      using multiple logistical regression analysis. RESULTS: Mean age was 76 years
      (range 50-101), 79% of patients were female and 65% had an extra articular
      fracture (AO33A). 8% were operated within 12h, 33% within 24h, 67% within 48h and
      83% within 72h. Educational level of surgeon was "attending or above as surgeon"
      in 56% of all cases and "attending or above as supervisor" in 33%. Mortality was
      7.1% at day 30 and 12.5% at day 90. The logistical regression analysis did not
      demonstrate any association between surgical delay or educational level of
      surgeon and mortality. Increasing age, male gender and ASA score >2 significantly
      increased both 30-day and 90-day mortality. CONCLUSION: No association between
      surgical delay or educational level of surgeon and mortality was found. These
      findings do not support the development of guidelines for decreasing surgical
      delay in this population.

PMID- 29050689
TI  - Acute lymphoblastic leukemia (ALL).

PMID- 29050690
TI  - How should we treat the AYA patient with newly diagnosed ALL?
AB  - Adolescent and young adult (AYA) patients with acute lymphoblastic leukaemia
      (ALL) are recognized as a unique population with specific characteristics and
      needs. In adolescents aged 15-20 years old, the use of full paediatric protocols
      is supported by many comparative studies of paediatric and adult cooperative
      groups. In young adults, growing evidence suggests that paediatric-inspired
      approaches may also improve outcomes and lead to long-term survival rates of
      almost 70%. In the last decade, better knowledge of ALL oncogenic landscape, age
      distribution, and minimal residual disease prognostic impact have improved risk
      stratification. New targets have emerged mostly in the heterogeneous subgroup of
      Philadelphia-like ALL and will require both in-depth molecular investigations and
      specific evaluations in rare subgroups of ALL. The remaining gap with the
      excellent results reported in children has many other contributing factors that
      should not be underestimated including late or difficult access to care, or poor
      adherence to treatment.

PMID- 29050691
TI  - Philadelphia chromosome negative B-cell acute lymphoblastic leukemia in older
      adults: Current treatment and novel therapies.
AB  - Older adults with Philadelphia chromosome negative (Ph-),-B-cell acute
      lymphoblastic leukemia (ALL) have the highest rates of treatment failure and
      treatment complications with current therapy, and, thus, there is no standard
      treatment for these patients. Approximately 16 percent of patients with newly
      diagnosed Ph- B-cell ALL are aged 60 years or older [1]. The five-year overall
      survival for this older cohort of patients is approximately 20 percent, and there
      has been no improvement in their survival in decades [2]. The challenge in
      managing older patients with ALL is achieving balance between efficacy of
      treatment and the toxicity of multi-agent chemotherapy. The latter approach is
      highly effective in younger adults, but greatly limited by toxicity in older
      adults. New classes of agents, bi-specific T-cell engager (BiTE) monoclonal
      antibody and antibody drug conjugates (ADC) have been introduced into the
      treatment of ALL, and these agents have achieved therapeutic responses and
      manageable toxicity in patients of all ages with relapsed refractory ALL. These
      newer immunotherapy agents may improve the treatment of older adults. This review
      focuses on the new approaches to treatment of Ph- B-cell ALL in older patients.
      Other reviews in this special edition of ALL will focus on Philadelphia
      chromosome positive ALL, Philadelphia-like ALL, and allogeneic stem cell
      transplant as related to older adults.

PMID- 29050692
TI  - Which tyrosine kinase inhibitor should we use to treat Philadelphia chromosome
      positive acute lymphoblastic leukemia?
AB  - The incorporation of tyrosine kinase inhibitors (TKIs) into chemotherapy regimens
      has significantly improved the long-term survival of patients with Philadelphia
      chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Successive
      generations of TKIs with increased potency against BCR-ABL and broader spectrum
      of activity against ABL kinase domain mutations have led to incremental
      improvements in the outcomes of patients with this disease. In particular,
      ponatinib, a potent pan-BCR-ABL TKI capable of overcoming the T315I mutation,
      holds significant promise in the treatment of Ph+ ALL, although the potential
      cardiovascular toxicity of this agent remains a concern. With the development of
      more potent TKIs that are capable of inducing deep and sustained remissions,
      future studies re-evaluating the need for intensive chemotherapy as well as the
      role for stem cell transplantation in first remission for patients with Ph+ ALL
      are warranted.

PMID- 29050693
TI  - How should we treat older adults with Ph+ adult ALL and what novel approaches are
      being investigated?
AB  - Treatment of older patients with Philadelphia-chromosome-positive (Ph+) acute
      lymphoblastic leukemia presents unique challenges. Advanced age, comorbidities,
      high treatment-related death rates with traditional chemotherapy, and relapse
      combine to yield poor survival. Reduced-intensity induction with BCR-ABL1
      targeted tyrosine kinase inhibitors (TKIs) and corticosteroids yields CR rates 96
      100% with no induction mortality but relapse is nearly certain without effective
      consolidation. Few clinical trials provide guidance on optimal consolidation for
      older Ph+ ALL. With second-generation TKIs, lower intensity chemotherapy after
      induction gives similar outcomes to intensive consolidation although long-term
      survival is still poor. Consolidation with allogeneic or autologous hematopoietic
      cell transplantation may improve survival for fit older patients. Novel targeted
      therapies like blinatumomab, inotuzumab ozogamicin, and CD19-targeted CAR T-cells
      hold promise to improve survival with reduced toxicity. Better understanding
      these approaches will require increased referral to specialized centers,
      expansion of clinical trials, and improved enrollment of older ALL patients on
      trials.

PMID- 29050694
TI  - The biology of Philadelphia chromosome-like ALL.
AB  - Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a
      recently described subtype of B-cell precursor ALL with a gene expression profile
      similar to Ph-positive ALL and a high frequency of IKZF1 alterations. The
      prevalence of Ph-like ALL increases with age, ranging from 10-15% of children to
      over 25% of young adults with ALL. It occurs more frequently in males and is
      associated with adverse clinical features including elevated minimal residual
      disease levels and poor survival in both children and adults. The genomic
      landscape of Ph-like ALL is characterized by a diverse range of genetic
      alterations that dysregulate cytokine receptor and kinase signaling pathways,
      including rearrangement of CRLF2 and other tyrosine kinases (predominantly ABL
      class and Janus kinases). Compelling preclinical data suggest patients harboring
      ABL-class rearrangements are candidates for ABL1-inhibitors, whilst alterations
      activating the JAK-STAT pathway may be amenable to treatment with JAK inhibitors.
      The success of combinatorial treatment of tyrosine kinase inhibitors with
      chemotherapy in Ph-positive ALL provides a framework for testing this approach in
      Ph-like ALL. Ongoing prospective studies will determine if incorporation of
      targeted therapy with intensive chemotherapy regimens will improve the outcome of
      patients with Ph-like ALL.

PMID- 29050696
TI  - Pharmacogenomics in acute lymphoblastic leukemia.
AB  - Pharmacogenomics is a fast-growing field of personalized medicine using a
      patient's genomic profile to determine drug disposition or response to drug
      therapy, in order to develop safer and more effective pharmacotherapy. Childhood
      acute lymphoblastic leukemia (ALL), being the most common malignancy in
      childhood, which is treated with uniform and standardized clinical trials, is
      remarkably poised for pharmacogenomic studies. In the last decade, unbiased
      genome-wide association studies have identified multiple germline risk factors
      that strongly modify host response to drug therapy. Some of these genomic
      associations (e.g. TPMT, NUDT15 and mercaptopurine dosing) have accumulated a
      significant level of evidence on their clinical utility such that they are
      warranted as routine clinical tests to guide modification of treatment. Most of
      these germline associations however, have not yet reached such actionability.
      Insights have also been gathered on germline factors that affect host
      susceptibility to adverse effects of antileukemic agents (eg, vincristine,
      asparaginase, methotrexate). Further large-scale studies are required, along with
      the assimilation of both germline and somatic variants, to precisely predict host
      drug response and drug toxicities, with the eventual aim of executing genomic
      based precision-pharmacotherapy in the treatment of ALL.

PMID- 29050695
TI  - How is the Ph-like signature being incorporated into ALL therapy?
AB  - Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a
      recently identified high risk disease subtype characterized by a gene expression
      profile similar to that observed in Philadelphia chromosome-positive (Ph
      positive) ALL, but without an underlying BCR-ABL1 translocation. Adults and
      children with Ph-like ALL harbor a diversity of alterations that all lead to
      activated kinase signaling. Outcomes for patients with Ph-like ALL are poor,
      which has prompted investigation into the role of tyrosine kinase inhibitor (TKI)
      based therapies for this disease. Several clinical trials are now ongoing that
      include screening for the Ph-like signature and treatment of patients with Ph
      like ALL with TKI therapy. This review examines how testing for Ph-like ALL is
      being incorporated into clinical trials.

PMID- 29050697
TI  - How do we measure MRD in ALL and how should measurements affect decisions. Re:
      Treatment and prognosis?
AB  - Minimal residual disease (MRD) is the most significant independent prognostic
      factor in acute lymphocytic leukemia (ALL). Monitoring MRD using sensitive
      techniques, including multiparametric flow cytometry (MFC) and quantitative
      polymerase chain reaction (qPCR)-based methods, has improved the assessment of
      treatment response and risk stratification for clinical management. New molecular
      methods, such as high-throughput next-generation sequencing (NGS), have evolved
      into routine laboratory tools to improve the sensitivity and specificity of MRD
      detection. It is essential to establish standardized protocols as to the timing
      of assessment and methodology used, to limit inter-laboratory variability. MRD
      has demonstrated utility for the identification of patients with suboptimal
      initial response to therapy who may benefit from more intensive or novel
      therapies, in addition to identifying patients with an excellent response to
      initial therapy who may be candidates for therapeutic reduction to limit
      toxicity. Herein, we review the methodological approaches to MRD detection in ALL
      and discuss the clinical implication of MRD in risk-directed therapy and
      practical issues.

PMID- 29050698
TI  - Which patients should I transplant with acute lymphoblastic leukemia?
AB  - Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia
      (ALL) offers curative therapy for patients who are in complete remission.
      Historically, there was great hesitation to offer this modality to patients with
      ALL due to the high attendant morbidity and mortality. Furthermore, the
      outstanding results in childhood ALL led many to believe that significant long
      term survival could be achieved using chemotherapy-based regimens alone. The
      International ALL Study jointly conducted by ECOG and MRC completely changed
      perceptions indicating, surprisingly to many, that transplantation - particularly
      for patients at standard risk - offered a significant survival advantage. There
      followed trials of more intensive chemotherapy demonstrating improved results
      that may obviate the need for allogeneic transplantation. While a certain
      controversy reigns, there are unequivocal high-risk scenarios where allogeneic
      transplantation still forms the core of curative therapy. Such transplants should
      be performed as early as possible in the course of the disease once remission has
      been obtained.

PMID- 29050699
TI  - How should we treat a patient with relapsed Ph-negative B-ALL and what novel
      approaches are being investigated?
AB  - Despite significant improvements in outcome of newly diagnosed B-precursor ALL,
      the results in relapsed or refractory adult ALL are overall poor. Large
      retrospective studies revealed significant differences in terms of outcome, with
      particularly poor response rates in early or refractory relapses, whereas late
      relapses usually respond very well to repeated standard induction. Particularly
      new immunotherapy compounds like the CD19 bispecific antibody Blinatumomab and
      the conjugated CD22 antibody Inotuzumab yielded promising response rates compared
      to standard therapies in randomised trials. Long-term survival is however still
      poor. The optimal use of these compounds remains to be defined. Chimeric antigen
      receptor T-cells are another promising treatment approach and multicenter
      clinical trials in adult ALL are awaited. For selected patients molecular
      directed therapies may have a role in relapsed ALL; standard diagnostic
      algorithms need to be defined. One of the major challenges is to define the role
      of stem cell transplantation after relapse. Whereas this procedure appears to be
      the only chance for cure, the mortality and relapse rate are still high and
      optimisation is urgently needed. Future strategies include optimised use of new
      compounds as part of combination regimens and the earlier treatment of upcoming
      relapse in the situation of persistent or recurrent minimal residual disease.

PMID- 29050700
TI  - The what, when and how of CAR T cell therapy for ALL.
AB  - Chimeric Antigen Receptor (CAR) T cells that have been engineered to target CD19
      have shown great promise in patients with relapsed and refractory B cell acute
      lymphocytic leukemia with remission rates of 70-90%. Some remissions have
      successfully bridged patients to a curable allogeneic stem cell transplant, some
      responses have been durable without further treatment, and some patients have
      achieved durable remissions for relapsed ALL after allogeneic stem cell
      transplant. Cytokine release syndrome, correlating with the in vivo activation
      and expansion of T cells, and neurologic toxicity are the most significant side
      effects and approaches to better understand and manage these events are the
      subject of ongoing clinical trials. The decision to intervene with CARTs requires
      an individualized approach taking into consideration patient, disease and therapy
      related factors.

PMID- 29050701
TI  - Cancer Immunotherapy and endocrinology: A new opportunity for multidisciplinary
      collaboration.

PMID- 29050702
TI  - Relationship between a fragmented QRS and microalbuminuria in patients with type
      2 diabetes mellitus.
AB  - INTRODUCTION: Microalbuminuria (MAU), a complication of diabetes, is closely
      related to cardiovascular events. A fragmented QRS (fQRS) in the
      electrocardiogram (ECG) was found to be strongly associated to cardiovascular
      morbidity and mortality. OBJECTIVE: The aim of this study was to assess the
      association between a fQRS and MAU in patients with type 2 diabetes mellitus
      (T2DM). PATIENTS AND METHODS: One hundred and twenty-seven patients (mean age,
      50.49 years; 44.01% male) with T2DM of at least six months duration and at least
      two urine albumin/creatinine ratios (ACRs) available were enrolled into the study
      between December 2015 and May 2016. All patients underwent ECG and
      echocardiography, and were taken blood and urine samples. Patients were divided
      into two groups according to presence of fQRS (group 1) or absence of fQRS (group
      2). RESULTS: Both groups had similar baseline characteristics. MAU and
      glycosylated hemoglobin (HbA1c) levels and left ventricular end-diastolic
      diameter (LVEDd) were increased in patients with a fQRS in the ECG (p=0.002,
      p=0.02, and p=0.007, respectively). Univariate and multivariate logistic
      regression analysis showed MAU and an increased LVEDd to be independent risk
      factors for the presence of a fQRS in the ECG of T2DM patients. DISCUSSION AND
      CONCLUSIONS: In this study, a fQRS was associated to MAU. In T2DM, MAU may be
      related to subclinical diastolic and systolic dysfunction.

PMID- 29050703
TI  - Validity of the Edinburgh claudication questionnaire for diagnosis of peripheral
      artery disease in patients with type 2 diabetes.
AB  - OBJECTIVE: To assess the prevalence of peripheral artery disease and the validity
      of clinical signs for its diagnosis in patients with type 2 diabetes. METHODS:
      Setting: Health center (Marinamansa,Orense). PERIOD: January 2011-January 2013.
      INCLUSION CRITERIA: Patients with type 2 diabetes, informed consent.
      MEASUREMENTS: Age, sex, diabetes duration, body mass index, Charlson index, blood
      pressure, ankle-brachial index (ABI), cholesterol levels, smoking. Cardiovascular
      risk (UKPDS). Edinburgh Claudication Questionnaire. SAMPLE SIZE: n=323 (+/- 5.5%
      accuracy, 95% confidence). STATISTICAL ANALYSIS: multivariate logistic regression
      analysis. Sensitivity, specificity, predictive values, and agreement were
      estimated. Informed consent and ethics committee approval were obtained
      (2010/278). RESULTS: Mean patient age was 71.56+/-12.73 years, and mean diabetes
      duration 12.38+/-9.96 years. Symptoms of intermittent claudication were reported
      by 26,4% of patients, ABI was normal (0.9-1.1) in 37.2% of patients, less than
      0.9 in 26,5%, and higher than 1.10 in 36.2% of patients. The kappa index of
      agreement of peripheral artery disease according to the Edinburgh Claudication
      Questionnaire and the ankle-brachial index was 0.33). The questionnaire showed a
      sensitivity of 50.7% for predicting the diagnosis of peripheral artery disease
      (ABI <0.9) with a specificity of 82.6%, with positive and negative predictive
      values of 48.6% and 83.8% respectively. CONCLUSIONS: One-fourth of patients with
      type 2 diabetes had peripheral artery disease. There was a low level of agreement
      between the evaluation of symptoms of intermittent claudication and the results
      of the ankle-brachial index. Presence or absence of symptoms of claudication did
      not allow for confirming or ruling out peripheral artery disease.

PMID- 29050704
TI  - Patterns of food avoidance and eating behavior in women with fibromyalgia.
AB  - INTRODUCTION: Fibromyalgia is a form of non-articular rheumatic disorder of
      unknown origin. It is characterized by widespread, chronic musculoskeletal pain.
      Patients with fibromyalgia suffer more frequently eating disorders, obesity,
      metabolic syndrome, and other gastrointestinal symptoms. Studies have pointed out
      to nutrition as a relevant factor in these patients. Some of them think that diet
      has an influence on fibromyalgia symptoms, and tend to adopt certain dietary
      patterns. This, combined with access to non-scientific information about diets
      and supplements, makes analysis of dietary behavior, avoidance, and restrictions
      particularly important. The aim of this study was to describe dietary habits and
      eating avoidance behaviors in patients with fibromyalgia, and to compare these
      data to those of a healthy sample of similar sociodemographic characteristics.
      METHODS: A descriptive case-control study was conducted in healthy subjects (n =
      60) age and sex-matched to the fibromyalgia group (n = 60), whose eating habits
      and restrictions were analyzed using a food frequency questionnaire, a
      sociodemographic questionnaire, and a food restriction scale. RESULTS: The group
      with fibromyalgia had significantly higher values in body mass index, weight
      fluctuation, use of herbal products, and development of diets, and significantly
      lower mean consumption of cereals, fruits, sugars, alcohol, and soft drinks.
      CONCLUSIONS: These results describe a sample of patients with fibromyalgia who
      follow a varied diet similar to that of healthy subjects, but more frequently
      avoid certain foods.

PMID- 29050705
TI  - Iodine nutritional status in Asturian schoolchildren.
AB  - INTRODUCTION: Iodine deficiency is a public health problem, and iodine
      nutritional status should therefore be regularly measured. OBJECTIVE: To
      ascertain iodine nutritional status in Asturias and its relation to use of
      iodized salt and to other sociodemographic and nutritional parameters. MATERIAL
      AND METHODS: A descriptive, observational study was conducted in a random sample
      of schoolchildren aged 5 to 14 years, in whom urinary iodine levels were measured
      by high-performance liquid chromatography. Families completed a survey on use of
      iodized salt, consumption of dairy products and fish, and sociodemographic data.
      RESULTS: The study sample consisted of 705 schoolchildren (51.1% females) with a
      mean age of 9.9 years (SD 2.6). In a total of 620 valid measurements, mean
      urinary iodine level was 204.1 MUg/L (SD 120.6), while the median value was 180.7
      MUg/L (P25-P75: 124-252.3 MUg/L, interquartile range 128.3 MUg/L). Urinary iodine
      levels were <100 MUg/L in 16.6% of children, and very low (<20 MUg/L) in 0.2%.
      Iodized salt was used in 69.3% of all households, and in all school canteens.
      Consumption of dairy products was significantly associated to urinary iodine
      levels (P<.0005). CONCLUSION: Iodine nutrition of Asturian schoolchildren is
      adequate, although the target of use of iodized salt in 90% of households is
      still far away. Adequate iodine nutrition may be due to other sources, such as
      dairy products. Public health campaigns are required to promote iodized salt
      consumption. Regular assessment of iodine nutritional status is also needed.

PMID- 29050706
TI  - Endocrine sequelae in childhood cancer survivors.
AB  - Thanks to the advances in cancer treatment, the five-year survival rate after
      childhood cancer has increased up to 80%. Therefore 1/500 young adults will be a
      survivor. Endocrine sequelae are most common, affecting 40-60% of survivors. The
      most frequent sequelae include growth failure and gonadal and thyroid diseases.
      Sequelae occur more frequently in survivors from central nervous system tumors,
      leukemia, and lymphoma. Their development will depend on the type of cancer, its
      location, age at diagnosis, and treatment administered. Treatments associated to
      more endocrine sequels are cranial radiotherapy and hematopoietic cell
      transplantation. Because of the high prevalence of endocrine sequelae,
      international guidelines recommend endocrinologists to prospectively evaluate the
      survivors. As some of these endocrine changes will not develop until adult life,
      transition programs should be implemented, and active investigation should be
      made to decrease the endocrine consequences of cancer treatment.

PMID- 29050707
TI  - ViDa1: a new questionnaire for measuring health-related quality of life in
      patients with type 1 diabetes.

PMID- 29050708
TI  - Hypercupremia secondary to oral contraceptives: report of 2 cases.

PMID- 29050709
TI  - Hypovitaminosis D: Searching for the evidence.

PMID- 29050710
TI  - Erratum to:"Microbiota y diabetes mellitus tipo 2".

PMID- 29050711
TI  - Prevalence of Vitamin D Deficiency in Pediatric Patients With Scoliosis Preparing
      for Spinal Surgery.
AB  - BACKGROUND: Establishing prevalence of vitamin D deficiency in elective scoliosis
      surgery may impact clinical outcomes. The objectives of this study were to
      document vitamin D status of patients with scoliosis preparing for surgical
      intervention in order to establish frequency of deficiency and determine
      characteristics influencing levels. METHODS: Records were queried for patients
      with scoliosis diagnosis who underwent posterior spinal fusion or initial growing
      rod placement and had serum vitamin 25 hydroxyvitamin D (D25) recorded in the
      preoperative period. Demographic data (gender, age, body mass index [BMI], race,
      scoliosis type, spine surgery procedure, and season of the year) were extracted.
      Chi-square analysis and multivariate modeling were used to evaluate deficiency
      status among various demographic categories and determine the demographic factors
      impacting D25. RESULTS: A total of 217 patients with a mean age of 13.6 +/- 3.6
      years had vitamin D levels drawn a mean of 38.7 +/- 20.6 days prior to surgery.
      The majority of the sample presented with a diagnosis of idiopathic scoliosis (n
      = 126), and most patients were scheduled for spinal fusion surgery (n = 192).
      Nearly 75% of the study population (n = 162) demonstrated D25 values below
      normal. African Americans presented with greater risk of deficiency (p < .0002)
      compared to Caucasians, as did patients preparing for spinal fusion versus
      growing rod placement (p < .03). Severe hypovitaminosis D was more common in
      winter than any other season (p < .005). Patients with neuromuscular scoliosis
      demonstrated significantly higher D25 levels over the idiopathic diagnosis type
      (p < .0002). Gender, BMI, and age did not impact D25. CONCLUSION: Low D25 levels
      are reported in pediatric patients with scoliosis preparing for corrective spinal
      surgery. Population subsets most at risk for deficiency in this limited study
      include African American children, those presenting for spinal fusion surgery,
      and patients admitted in winter season.

PMID- 29050712
TI  - A Case-Control Study of Body Composition, Prevalence, and Curve Severity of the
      Patients With Adolescent Idiopathic Scoliosis in the East Part of China.
AB  - OBJECTIVE: The purpose of the study is to investigate the characteristics of
      prevalence and curve severity in patients with adolescent idiopathic scoliosis
      (AIS) and the body composition alterations between the patients with AIS and
      healthy controls. METHODS: Information on the study sample was obtained from a
      screening database. The AIS cohort was paired with an age- and gender-matched
      healthy cohort. The stratification of BMI and curve severity was conducted
      according to the criteria developed by the US Centers for Disease Control and
      Prevention and the Scoliosis Research Society. The prevalence and curve severity
      of the patients with AIS were investigated. Multigroup comparison of body
      composition parameters was conducted according to BMI between the patients with
      AIS and healthy controls. RESULTS: A total of 1,202 patients with AIS and an age-
      and gender-matched cohort were recruited from local schools. The underweight
      cases had the highest prevalence of AIS and significantly higher Cobb angle
      compared with the other three BMI subgroups. Although the patients with AIS had
      lower body weight, body fat mass, percentage of body fat, and fat-free mass
      compared with healthy controls, converse results were observed in the underweight
      cases after stratification according to BMI. CONCLUSION: Based on the sporadic
      body composition of the patients with AIS observed in the current study, it is
      predictable that the pathophysiological alterations may be different before and
      after the onset of scoliosis. Well-designed human or animal studies for
      underweight patients would be helpful to reveal the mechanisms of
      pathophysiological alterations and better predict the development of AIS.

PMID- 29050713
TI  - Is Preoperative Fibrinogen Testing Associated With Total Blood Loss in Adolescent
      Idiopathic Scoliosis Correction?
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: This study sought to investigate
      the potential association between preoperative fibrinogen, bleeding, and
      transfusion requirements in adolescent idiopathic scoliosis (AIS) corrections.
      SUMMARY OF BACKGROUND DATA: Blood loss after major spinal reconstruction
      increases the risks and costs of surgery. Preoperative fibrinogen levels may
      predict intra- and postoperative blood loss. METHODS: Data were collected from
      clinic charts and hospital medical records of all 110 of a single surgeon's
      consecutive AIS patients undergoing greater than three-level deformity correction
      surgeries from January 2011 to December 2013. Pearson test was used to
      investigate the correlation between bleeding and clinical variables, with level
      of significance set at alpha = 0.05. RESULTS: Mean total bleeding volume was 488
      (+/-356) mL. Overall, mean preoperative fibrinogen concentration was 188.6 +/-
      32.8 mg/dL. Preoperative platelet counts, prothrombin time (PT), and activated
      partial thromboplastin time (aPTT) did not correlate significantly with
      preoperative fibrinogen concentration (p > .05). Both packed red cells (PRC) and
      packed red blood cells (PRBC) correlated significantly with preoperative
      fibrinogen (p < .05). The correlation between PRC and preoperative fibrinogen was
      -0.042. There was a negative correlation between PRBC and preoperative fibrinogen
      (r = -0.46). Overall mean thromboelastography (TEG) values were within normal
      range in both males and females and both had comparable TEG parameter values. All
      the TEG variables (G, K, and Angle) correlated significantly with preoperative
      fibrinogen (p < .05) but not with total blood volume (p > .05). The correlation
      coefficient between these TEG variables and preoperative fibrinogen were 0.51,
      0.59, and 0.54, respectively. The total bleeding volume and % estimated blood
      volume correlated significantly with both PRC (r = 0.352, r = 0.376; p < .05) and
      PRBC (r = 0.621, r = 0.614; p < .05). CONCLUSIONS: In our cohort undergoing
      correction of AIS, preoperative fibrinogen levels exhibited a significant
      negative logarithmic correlation with total blood loss. TEG variables also
      correlated significantly with preoperative fibrinogen levels. Efforts should be
      made to incorporate this measure in perioperative blood management program for
      AIS corrections. LEVEL OF EVIDENCE: Level IV.

PMID- 29050714
TI  - When Does Intraoperative Blood Loss Occur During Pediatric Scoliosis Correction?
AB  - BACKGROUND: The purpose of our study was to assess the relationship between
      amount of blood loss and surgical stage in pediatric patients undergoing
      posterior spinal fusion for deformity correction to determine: (1) when the
      highest rate of blood loss occurred; (2) what percentage of total blood loss
      occurred during deformity correction and closure; and (3) how to predict
      remaining blood loss during a procedure. Blood loss following exposure and
      placement of the final pedicle screw is often underestimated, which may result in
      lack of sufficient blood product availability. Knowledge of the rate of blood
      loss plays an important role in intraoperative decision making, facilitating
      communication with the anesthesia team, and improving patient safety. METHODS:
      Clinical records were reviewed for all patients 9 to 18 years of age who
      underwent index spinal fusion surgery with pedicle screw constructs for deformity
      correction of greater than 4 levels by a single surgeon from April 2013 to July
      2015. All patients received tranexamic acid prophylactically. Exclusion criteria
      included vertebral column resections, cell saver use, cases complicated by signal
      loss on monitoring, and incomplete records. Sixty-two of 99 patients met criteria
      and were included in data analysis. The surgery was divided into four stages:
      exposure, screw/anchor placement, corrective procedures (reduction, osteotomies),
      and closure. Normalized blood loss (NBL) was calculated by adjusting actual blood
      loss for patient weight and number of levels fused. Demographic factors of age,
      sex, weight/BMI, diagnosis, preoperative Cobb angle, and number of levels fused
      were accounted for and autoregressive moving average was used to assess whether
      NBL varied significantly at different stages of the procedure. RESULTS: NBL
      during reduction and closure (1.69) was significantly greater than NBL during
      exposure and screw placement (1.49) (p < .040). The rate of blood loss was also
      highest during reduction/deformity correction procedures than exposure (p <
      .001), anchor placement (p = .010), and closure (p < .010). At the time of
      placement of the final pedicle screw, 47% of the total blood loss for the case
      had occurred. CONCLUSIONS: Rate of blood loss varies during pediatric posterior
      spinal deformity correction surgery, with the highest rates occurring during the
      reduction portion of the operation. Just over half of the total EBL occurs during
      the reduction and closure stages of surgery requiring the surgical team to plan
      accordingly. Additional studies investigating modifiable factors affecting blood
      loss during the later stages of scoliosis surgery are warranted.

PMID- 29050715
TI  - The Effect of Two Attending Surgeons on Patients With Large-Curve Adolescent
      Idiopathic Scoliosis Undergoing Posterior Spinal Fusion.
AB  - STUDY DESIGN: Retrospective, chart review. OBJECTIVES: The objective of this
      study is to investigate the impact of using two surgeons for posterior spinal
      fusion (PSF) in patients with AIS with large-magnitude curves (greater than 70
      degrees ). SUMMARY OF BACKGROUND DATA: Previous studies have shown that
      intraoperative risk factors can be reduced by having two surgeons operate
      simultaneously. METHODS: A retrospective chart review identified 47 patients
      between January 1, 2009, and December 31, 2014, who underwent a posterior spinal
      fusion (PSF) with AIS with large-magnitude curves (greater than 70 degrees ).
      Patients with large-magnitude curves due to neuromuscular diseases or any defined
      pathology other than idiopathic scoliosis were excluded, as well as patients with
      kyphotic or kyphoscoliotic curves. RESULTS: There was no statistical difference
      between the total operative time, anesthesia time, estimated blood loss (EBL),
      %EBL, and blood transfusion units. Total operative time for the two-surgeon group
      and single-surgeon group was 212.11 and 238.07 minutes, respectively (p = .078).
      The two-surgeon group averaged 0.26 blood transfusion units versus 0.39 units for
      the single-surgeon group (p = .50). Average hospital length of stay was decreased
      in the two-surgeon group (5.16 vs. 6.82 days, p = .002). CONCLUSIONS: The use of
      two surgeons for PSF for AIS has previously been shown to decrease operative time
      and blood loss, factors that are correlated with prolonged hospital stay and
      increased risk of both neurologic and nonneurologic complications. However, in
      this study, the technique of having two experienced orthopedic spine surgeons
      work simultaneously to perform pedicle screw-only posterior spinal fusion on
      large-magnitude AIS curves greater than 70 degrees  did not improve blood loss or
      operative time. Further study needs to continue to identify ways to minimize
      complications for patients who undergo spinal fusion. LEVEL OF EVIDENCE: Level
      III, retrospective, comparative study.

PMID- 29050716
TI  - Postoperative Spine Dressing Changes Are Unnecessary.
AB  - INTRODUCTION: There is minimal literature regarding when dressing changes should
      be performed. We present the dressing change protocol adopted by our institution.
      The purpose of this study was to provide an update of our experience with this
      dressing change protocol over a 15-year period. METHODS: Effective January 2005,
      we implemented our universal protocol of no dressing changes for five days after
      surgery. Reviewing a health system administrative database, all spine surgery
      cases involving instrumentation performed at our institution were captured.
      Surgical site infection (SSI) cases: superficial, deep, and organ space as
      defined by the Centers for Disease Control and Prevention (CDC), were identified
      by reviewing an infection control database. Fisher exact test was used to compare
      SSI rates in all instrumented fusion cases from January 1999 to December 2004
      (prior to implementation of the dressing change protocol) to those from January
      2005 to December 2013 (after the protocol was initiated). RESULTS: A total of
      8,631 instrumented spine fusions were performed at a single institution from 1999
      to 2013. Overall, after instituting our universal no-dressing-change protocol,
      SSI rates for all cervical, thoracic, and lumbar instrumented cases combined
      decreased from 3.9% (97/2473) to 0.93% (57/6158) (p < .0001). The reduction in
      SSI rates was most significant for posterior cervical and posterior lumbar
      surgeries. After our dressing change protocol was implemented, we saw an
      improvement in SSI rates for posterior cervical instrumented cases from 3.2%
      (6/186) to 0.50% (4/815) (p = .0041). Posterior lumbar instrumented fusion SSI
      rates dropped from 5.5% (65/1179) to 1.1% (32/2890) (p < .0001). CONCLUSION:
      Dressing changes in the immediate postoperative period are not necessary.
      Applying a sterile dressing in the operating room may serve as a barrier to
      nosocomial pathogens during hospitalization. Our data suggest this dressing
      change protocol may lead to reduced SSI risk. Leaving the original postoperative
      surgical dressing intact is safe, simple, and cost-effective.

PMID- 29050717
TI  - Radiographic and Functional Outcome in Adolescent Idiopathic Scoliosis Operated
      With Hook/Hybrid Versus All-Pedicle Screw Instrumentation-A Retrospective Study
      in 149 Patients.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare radiographic
      outcome and health-related quality of life in patients with adolescent idiopathic
      scoliosis (AIS) treated with hook/hybrid (H/H) or all-pedicle screw (PS)
      instrumentation. SUMMARY OF BACKGROUND DATA: PS instrumentation has largely
      replaced H/H in the surgical treatment of AIS but whether a normalized sagittal
      profile can be obtained with the PS construct is still debated. Additionally,
      comparative studies assessing HRQL and surgical complications are needed.
      METHODS: Two consecutive series of surgically treated AIS patients were included.
      Surgical treatment consisted of H/H or low-profile all-PS instrumentation.
      Radiographic and clinical follow-up, including SRS-22r questionnaires, was
      performed a minimum of two years postoperatively. RESULTS: There were 85 and 64
      patients in the H/H and PS group, respectively. The groups did not differ on
      baseline parameters apart from a lower flexibility in the H/H group (34% +/- 14%
      vs. 39% +/- 14% in the PS group, p = .026). Mean curve correction at final follow
      up was 31% +/- 13% versus 49% +/- 12% in the H/H and PS group, respectively (p <
      .001), and mean loss of correction was 7 degrees  versus 4 degrees  (p < .001).
      The Cincinnati correction index was significantly higher in the PS group at final
      follow-up (p < .001). Postoperative thoracic kyphosis was significantly higher in
      the H/H group (27 degrees  +/- 11 degrees  vs. 22 degrees  +/- 11 degrees  in the
      PS group) with a mean change in kyphosis of 3 degrees  +/- 9 degrees  versus -3
      degrees  +/- 12 degrees  in the H/H and PS group, respectively. SRS-22 scores did
      not differ between the two groups (p > .090), and the reoperation rate at final
      follow-up was 9% in the H/H group and 6% in the PS group (p = .556). CONCLUSIONS:
      In a large consecutive cohort of AIS patients followed for a minimum of two
      years, we found a significantly better curve correction and less loss of
      correction with PS instrumentation compared to H/H. There was no significant
      difference in SRS-22r scores at final follow-up. LEVEL OF EVIDENCE: Level III.

PMID- 29050718
TI  - Timing of Changes in Three-Dimensional Spinal Parameters After Selective Thoracic
      Fusion in Lenke 1 Adolescent Idiopathic Scoliosis: Two-Year Follow-up.
AB  - STUDY DESIGN: Retrospective analysis of the prospectively collected data.
      OBJECTIVE: To investigate the relationship between the axial rotation of the
      unfused lumbar spine and the parameters of the instrumented thoracic spine at
      varying time points after selective thoracic fusion (STF) in Lenke 1B and 1C
      adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The impact of
      STF on the spontaneous lumbar curve correction in AIS has been studied mainly in
      the frontal planes. The relationship between the spontaneous transverse plane
      correction of the lumbar spine and the parameters of the fused thoracic spine is
      not well documented. METHODS: Twenty-one Lenke 1B and 1C patients who had
      received STF with minimum two years' follow-up were selected. Thoracic and lumbar
      Cobb angles, kyphosis, lordosis, and thoracic and lumbar apical vertebrae
      rotations were measured at preoperative, first-erect, six-month, one-year, and
      two-year follow-ups. The association between the lumbar apical vertebral rotation
      and other thoracic and lumbar variables at different time points were determined
      using regression analysis. The variables significantly predicting the lumbar
      axial rotation correction at two years were determined from the preceding follow
      up visits. RESULTS: Kyphosis, thoracic Cobb, thoracic apical vertebral rotation,
      and lumbar Cobb were significantly different between the preoperative and all the
      postoperative follow-ups (p < .05). At the two-year follow-up, a decrease in
      thoracic rotation and lumbar Cobb and a higher residual thoracic Cobb were
      associated with an improved spontaneous lumbar rotation (R2 = 0.41, p < .05).
      Lumbar rotation at two years was predicted from thoracic derotation and lumbar
      Cobb at first erect (R2 = 0.30, p < .05). CONCLUSION: Spontaneous lumbar curve
      rotation correction correlated to the fused and unfused spinal parameters in the
      three anatomic planes. The relationship between thoracic and lumbar rotation
      persist up to two years after STF. Thoracic derotation is an important factor
      determining the lumbar rotation correction at two years after STF.

PMID- 29050719
TI  - How Is Pulmonary Function and Exercise Tolerance Affected in Patients With AIS
      Who Have Undergone Spinal Fusion?
AB  - STUDY DESIGN: Prospectively enrolled AIS patients who underwent spinal fusion,
      with 2 year follow-up. OBJECTIVES: To evaluate the cardiovascular fitness and
      activity level in patients with AIS pre- and post-spinal fusion and to determine
      if initial curve magnitude or pulmonary function is predictive of exercise
      capacity. SUMMARY OF BACKGROUND DATA: Researchers have tried to link pulmonary
      function testing (PFT) to exercise capacity; the results are mixed. Some report
      no improvement in PFTs or aerobic activity after surgical correction, and PFT
      measures were not predictive of exercise capacity. Conflicting results have shown
      Vo2max results to fall within normal range in AIS patients while PFTs show
      minimal impairment. METHODS: AIS patients underwent PFT and oxygen consumption
      (VO2) testing during a submaximal graded exercise test (GXT) pre- and post-spinal
      fusion. Vo2max was predicted in those patients who completed the test to 85% of
      maximal heart rate. Pre- to postoperative changes were assessed and then compared
      to age-matched control subjects. Correlations between Vo2max and curve severity,
      pulmonary function, and activity level were assessed. RESULTS: Thirty-seven
      patients participated. Vo2max was predicted in 23 patients pre- and
      postoperation. There was a significant reduction in Vo2max postfusion (39.5 +/-
      6.5 mL/kg/min vs 42.1 +/- 8.1 mL/kg/min, p = .033); however, compared with
      controls (40.5 +/- 6.5 mL/kg/min), all data were within the normal range (p >
      .05). AIS patients reporting high activity had significantly greater Vo2max than
      those reporting low activity both pre and postoperatively, but this difference
      only met statistical significance preop (p < .05). Curve magnitude and PFT
      measures were not found to correlate with Vo2max (p > .05). CONCLUSIONS: Vo2max
      in patients with AIS is within normal range both pre- and postfusion. Pulmonary
      limitations are accommodated for with a slightly increased breathing rate and a
      slightly reduced overall workload. Activity level rather than curve severity
      affects Vo2max outcomes following fusion in AIS.

PMID- 29050720
TI  - Does Intrathecal Baclofen Therapy Increase Prevalence and/or Progression of
      Neuromuscular Scoliosis?
AB  - STUDY DESIGN: Retrospective, case-matched review. OBJECTIVES: Compare a group of
      individuals with cerebral palsy (CP) who had intrathecal baclofen (ITB) pumps to
      a group of individuals with CP who did not have ITB pumps in order to determine
      if there was a difference in the prevalence of new-onset neuromuscular scoliosis,
      an increased rate of progression of preexisting neuromuscular scoliosis, or an
      increased rate of posterior spine fusion surgery in skeletally immature
      individuals with CP who had ITB pumps. SUMMARY OF BACKGROUND DATA: Various
      authors report conflicting findings, with some reporting an increased incidence
      or prevalence of scoliosis in individuals with CP who have ITB pumps whereas
      others report no difference in the rate of scoliosis between groups. METHODS:
      Retrospective chart and radiographic case-matched study in which individuals were
      matched by gender and Gross Motor Function Classification Scale (GMFCS) level.
      RESULTS: We found no difference in the rates of new-onset neuromuscular scoliosis
      for those with CP and ITB pumps and those without ITB pumps. However, we did see
      a higher rate of progression as well as an increased rate of posterior spine
      fusion surgery in individuals with CP who had ITB pumps than for those with CP
      who did not have an ITB pump. CONCLUSIONS: We continue to recommend ITB pump
      therapy for individuals with severe spasticity associated with CP (GMFCS IV and
      V). There is a significant risk of complications for individuals in general. The
      risk of neuromuscular scoliosis is relatively high in this population. Our
      findings suggest that individuals with CP who have ITB pumps and who do or do not
      have preexisting scoliosis should be monitored closely for either developing new
      neuromuscular scoliosis or progression of preexisting scoliosis.

PMID- 29050721
TI  - Acute Kidney Injury Secondary to Cell Saver in Posterior Spinal Fusion.
AB  - BACKGROUND: Autologous blood transfusion, commonly referred to as cell saver, is
      frequently used in spinal fusion to salvage red blood cells because of the risk
      of significant intraoperative blood loss. This case report describes a case of
      acute kidney injury (AKI) secondary to cell saver use. Our objective is to
      increase the knowledge about the process of red blood cell salvage and this
      exceedingly rare complication. METHODS: Chart and renal biopsy results for a
      single case were reviewed and reported in this retrospective study. RESULTS: A
      healthy 18-year-old male patient underwent posterior spinal instrumentation and
      fusion for adolescent idiopathic scoliosis with utilization of intraoperative
      autologous blood transfusion. The patient subsequently developed hematuria and
      AKI with a peak creatinine of 13.9 mg/dL. An extensive clinical workup, including
      autoimmune serology, excluded any identifying causes. A renal biopsy showed
      pigment-induced acute tubular necrosis. CONCLUSIONS: This case, to our knowledge,
      is the first and only case report of AKI secondary to cell saver demonstrated by
      renal biopsy. The literature has shown both the benefit of cell saver by
      decreasing the need for allogeneic transfusion and the risk of transient
      hematuria. However, this case demonstrates the importance of monitoring patients
      for potential complications.

PMID- 29050722
TI  - Adjacent Segment Disease 44 Years Following Posterior Spinal Fusion for
      Congenital Lumbar Kyphosis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report the clinical and imaging findings
      of a patient with lumbar stenosis 44 years after posterior spinal fusion for
      congenital lumbar kyphosis. SUMMARY OF BACKGROUND DATA: To our knowledge, there
      are no long-term follow-up reports after posterior spine fusion (PSF) for
      congenital kyphosis. Congenital kyphosis is an uncommon deformity with the
      potential to progress rapidly and result in deformity and neurologic deficits.
      METHODS: We report the patient's history, physical examination, imaging findings,
      and management in addition to providing a literature review. RESULTS: A 54-year
      old-male who underwent T8-L3 PSF in 1972 because of congenital kyphosis presented
      44 years after surgery with lower back pain, buttock, and bilateral posterior leg
      pain. On physical examination, no weakness was elicited and magnetic resonance
      imaging demonstrated L4-L5 lumbar stenosis. The patient was enrolled in physical
      therapy and responded well to medical/interventional management. CONCLUSION: To
      our knowledge, this is the longest follow-up of surgical management of congenital
      lumbar kyphosis. Posterior fusion only halted the progression of the kyphosis
      with subsequent developed of adjacent segment disease distal to the fusion. LEVEL
      OF EVIDENCE: Level IV.

PMID- 29050723
TI  - [Scalp lipedema].
AB  - BACKGROUND: Lipedematous scalp, with or without alopecia, is a poorly known and
      rarely reported entity. It was first described in 1935 by Cornbleet. It involves
      increased thickness of the subcutaneous tissue of the scalp, responsible for an
      overall thickening of the scalp, which may be associated with alopecia, pruritus
      or painful sensations. Currently, fewer than 50 cases of lipedematous scalp, both
      with and without alopecia, have been reported in the literature. PATIENTS AND
      METHODS: Herein we present the case of a 36-year-old woman from the Ivory Coast,
      who presented scalp pain associated with infiltration of the entire subcutaneous
      tissue of the scalp seen clinically and confirmed at MRI. Histology added
      nothing. DISCUSSION: We diagnosed a new case of lipedematous scalp in an African
      woman. No cause was found. Therapeutic abstention appears the best management
      strategy.

PMID- 29050724
TI  - [Neutrophilic dermatosis of the dorsum of the hands after a rabbit scratch].

PMID- 29050725
TI  - Evaluation of mean transit time of aerosols from the area of origin to the Arctic
      with 210Pb/210Po daily monitoring data.
AB  - In this study, the activity concentrations of 210Pb and 210Po on the 22 daily air
      filter samples, collected at CTBT Yellowknife station from September 2015 to
      April 2016, were analysed. To estimate the time scale of atmospheric long-range
      transport aerosol bearing 210Pb in the Arctic during winter, the mean transit
      time of aerosol bearing 210Pb from its origin was determined based on the
      activity ratios of 210Po/210Pb and the parent-progeny decay/ingrowth equation.
      The activity ratios of 210Po/210Pb varied between 0.06 and 0.21 with a median
      value of 0.11. The aerosol mean transit time based the activity ratio of
      210Po/210Pb suggests longer mean transit time of 210Pb aerosols in winter (12 d)
      than in autumn (3.7 d) and spring (2.9 d). Four years 210Pb and 212Pb monitoring
      results and meteorological conditions at the Yellowknife station indicate that
      the 212Pb activity is mostly of local origin, and that 210Pb aerosol in
      wintertime are mainly from outside of the Arctic regions in common with other
      pollutants and sources contributing to the Arctic. The activity concentration
      ratios of 210Pb and 212Pb have a relatively constant value in summer with a
      significant peak observed in winter, centered in the month of February.
      Comparison of the 210Pb/212Pb activity ratios and the estimated mean 210Pb
      transit time, the mean aerosol transit times were real reflection of the
      atmosphere transport characteristics, which can be used as a radio-chronometer
      for the transport of air masses to the Arctic region.

PMID- 29050726
TI  - Preface.

PMID- 29050727
TI  - Surgical treatment of active native mitral infective endocarditis: A meta
      analysis of current evidence.
AB  - BACKGROUND: The native mitral lesion of active infective endocarditis implies a
      poor prognosis and is associated with adverse short- or long-term results without
      surgical treatment. Both mitral valvuloplasty (MVP) and mitral valve replacement
      (MVR) have been performed in the treatment of active native mitral infective
      endocarditis (ANMIE). However, the outcomes of the two approaches remain unclear.
      The aim of this study was to systematically review the two procedures with
      mortality and survival as the primary endpoints. METHODS: A systematic review of
      the literature was conducted to identify all relevant studies with comparative
      data on MVP versus MVR for the treatment of ANMIE. Information on baseline
      characteristics of patients, operation method, quality of literature, follow-up,
      and so forth was abstracted using standardized protocols. Pooled odds ratio (OR)
      or hazard ratio (HR) was calculated and possible publication bias was tested.
      RESULTS: Nine comparative observational studies with a total of 633 patients (MVP
      = 265, MVR = 368) were identified for qualitative assessment, data extraction,
      and analysis. The summary OR for operative mortality, comparing repair with
      replacement, was 0.37 (95% CI 0.0.18-0.80; p = 0.0005). Summary 1- and 5-year HRs
      for event-free survival were 0.43 (95% CI 0.20-0.92; p = 0.03) and 0.44 (95% CI
      0.25-0.77, p = 0.004), respectively (repair vs. replacement). Summary 1- and 5
      year survival HRs were 0.51 (95% CI 0.24-1.08; p = 0.08) and 0.55 (95% CI 0.32
      0.96; p = 0.004), respectively (repair vs. replacement). No heterogeneity was
      revealed between studies, and possible publication bias was insignificant.
      CONCLUSIONS: This meta-analysis suggests that MVP may be associated with superior
      postoperative survival outcomes compared with MVR. MVP is desirable, if possible,
      as a durable alternative to replacement. However, we must consider the influence
      of different patient characteristics and surgeons' preferences on the choice of
      surgical approach, and additional powered clinical trials will be required to
      confirm these findings.

PMID- 29050728
TI  - SIRT1 acts as a potential tumor suppressor in oral squamous cell carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant
      tumor in oral cancer, however, the mechanism underlying OSCC tumorigenesis is
      unknown. SIRT1, has been considered a prominent tumor-suppressing/promoting gene
      in various solid tumors, although the precise role of SIRT1 in OSCC progression
      remains unknown. METHODS: SIRT1 expression was assessed in surgically resected
      specimens from patients with OSCC for histopathologic factors. SIRT1 levels in
      OSCC were determined, SIRT1 overexpression was achieved on transfecting OSCC
      cells with a SIRT1-containing plasmid, followed by evaluation of proliferative
      ability and invasiveness of these cells. RESULTS: SIRT1 levels were significantly
      lower in patients with OSCC than in controls (p < 0.05). Moreover, SIRT1 levels
      in patients with OSCC were significantly associated with the lymphovascular
      permeation but not with the sex, age, stage and location. Furthermore, SIRT1
      overexpression inhibited proliferation and invasion in OSCC cells. CONCLUSION:
      The present results suggest that SIRT1 is a potential tumor suppressor in OSCC.

PMID- 29050729
TI  - Evaluating blood and excrement as bioindicators for metal accumulation in birds.
AB  - Birds are widely used to assess metal contamination in the environment and there
      are different approaches to determine the exposure level in individuals, some
      being destructive (collection of soft tissues) and some non-destructive (blood,
      feathers and excrement). The use of blood to detect internal concentrations of
      metals is an acknowledged method, but to what extent blood can predict the
      concentrations in soft tissues has been less well evaluated in wild terrestrial
      birds. The same is true for excrements. This study compares the non-destructive
      methods using blood and excrement with liver sampling, with respect to exposure
      and accumulation of the elements arsenic, cadmium, copper, lead and zinc in
      nestling pied flycatchers (Ficedula hypoleuca). Blood, liver and excrement
      reflected the environmental exposure of non-essential elements and were
      independent of nestling sex. There were asymptotic relationships between the
      concentration of arsenic, cadmium and lead in liver and blood, excrement and
      liver, and excrement and blood, but none for copper or zinc. Those relationships
      were generally stronger between liver and blood than between excrements and
      internal concentrations. Lead had the strongest associations for all matrixes.
      The conclusion is that blood is an appropriate tool to assess accumulation of
      arsenic, cadmium and especially lead, but that blood can underestimate the
      accumulation at highly contaminated sites. Excrement can also give an indication
      of metal accumulation, but may overestimate internal concentrations at high
      exposure, and individual variability makes direct comparisons between these
      matrices less appropriate.

PMID- 29050730
TI  - Monitoring atmospheric nitrogen pollution in Guiyang (SW China) by contrasting
      use of Cinnamomum Camphora leaves, branch bark and bark as biomonitors.
AB  - Moss (as a reference material) and camphor (Cinnamomum Camphora) leaf, branch
      bark and bark samples were systematically collected across an urban-rural
      gradient in Guiyang (SW China) to determine the efficacy of using these bio
      indicators to evaluate nitrogen (N) pollution. The tissue N concentrations (0.13%
      2.70%) and delta15N values (-7.50/00 to +9.30/00) of all of these bio-indicators
      exhibited large spatial variations, as they recorded higher values in urban areas
      that quickly decreased with distance from the city center; moreover, both soil N
      concentrations and soil delta15N values were found no significant differences
      within each 6 km from the urban to the rural area. This not only suggests that
      the different N uptake strategies and variety of N responses of these bio
      indicators can be reflected by their different susceptibilities to variations in
      N deposition but also reveals that they are able to indicate that urban N
      deposition is mostly from traffic and industry (NOx-N), whereas rural N
      deposition is mainly from agriculture (NHx-N). Compared to previously collected
      urban moss and camphor leaf samples, the significantly increased delta15N values
      in current urban moss and camphor leaf samples further indicate a greater
      contribution of NOx-N than NHx-N to urban N deposition. The feasibility of using
      the N concentrations and delta15N values of branch bark and bark as biomarkers of
      N deposition thus was further confirmed through the comparative use of these bio
      indicators. It can be concluded that vascular plant leaves, branch bark and bark
      can be used as useful biomonitoring tools for evaluating atmospheric N pollution.
      For further study, quantitative criteria for the practical use of these bio
      indicators in response to N deposition should be developed and the differences in
      the delta15N values of different plant parts should also be considered,
      particularly in urban environments that are severely disrupted by atmospheric
      pollution.

PMID- 29050731
TI  - Spatial avoidance to experimental increase of intermittent and continuous sound
      in two captive harbour porpoises.
AB  - The continuing rise in underwater sound levels in the oceans leads to disturbance
      of marine life. It is thought that one of the main impacts of sound exposure is
      the alteration of foraging behaviour of marine species, for example by deterring
      animals from a prey location, or by distracting them while they are trying to
      catch prey. So far, only limited knowledge is available on both mechanisms in the
      same species. The harbour porpoise (Phocoena phocoena) is a relatively small
      marine mammal that could quickly suffer fitness consequences from a reduction of
      foraging success. To investigate effects of anthropogenic sound on their foraging
      efficiency, we tested whether experimentally elevated sound levels would deter
      two captive harbour porpoises from a noisy pool into a quiet pool (Experiment 1)
      and reduce their prey-search performance, measured as prey-search time in the
      noisy pool (Experiment 2). Furthermore, we tested the influence of the temporal
      structure and amplitude of the sound on the avoidance response of both animals.
      Both individuals avoided the pool with elevated sound levels, but they did not
      show a change in search time for prey when trying to find a fish hidden in one of
      three cages. The combination of temporal structure and SPL caused variable
      patterns. When the sound was intermittent, increased SPL caused increased
      avoidance times. When the sound was continuous, avoidance was equal for all SPLs
      above a threshold of 100 dB re 1 MUPa. Hence, we found no evidence for an effect
      of sound exposure on search efficiency, but sounds of different temporal patterns
      did cause spatial avoidance with distinct dose-response patterns.

PMID- 29050732
TI  - [Epidemiology of early repolarization pattern in Maghreb].
AB  - : An early repolarization variant (ERV) in inferolateral leads has recently been
      associated with vulnerability to ventricular fibrillation. These studies have
      been conducted in the occidental countries. The prevalence of ERV in the
      population of the Maghreb is unknown. The aim of this study was to evaluate the
      prevalence and risk factors of ERV in a young population from Algeria. METHODS:
      We assessed the prevalence of ERV within a population of 441 healthy subjects
      (mean age 25 years) using 12-lead electrocardiography. ERV was stratified by
      three independent cardiologists according to the J-point elevation (>=0.1mV) in
      the inferior, apicolateral or both leads with QRS slurring or notching. RESULTS:
      The inferolateral ERV pattern was present in 55 subjects (12.4%). A malign ERV
      (>2mm) was present in 5 subjects (9% of ER) and ER in inferior and lateral leads
      in 40% of ER. An ERV pattern was more frequently associated with young age, male,
      bradycardia and T wave in V1 lead. CONCLUSION: An ERV is a common finding in a
      healthy Algerian young population. This prevalence seems to be more important
      than other studies due to young age and not to a racial difference. Our
      population were more at risk that other studies, and we found more T waves in V1
      lead in this people, due to an ethnic particularities or a phenotypic association
      with the Brugada syndrome.

PMID- 29050733
TI  - [Rhythmology in hospital centres in France].

PMID- 29050734
TI  - [Five years assessment of cardiac stimulation in two public hospitals in Burkina
      Faso: An experiment of collaboration with two hospitals in Auvergne].
AB  - OBJECTIVES: Cardiac stimulation becomes a reality in Burkina Faso. The aim of our
      study was to evaluate this activity over five years and to appreciate the impact
      of collaboration with French hospitals of Auvergne area in its development.
      MATERIALS AND METHODS: Prospective study including consecutively patients who
      underwent pacemaker implantation since June 2011. Data collected included
      indications, time to care, type of stimulation, complications, cost of treatment,
      and education and quality of life of the patient. RESULTS: Sixty-nine patients
      received definitive pacemaker from June 2011 to June 2016, of whom 45.5% were
      women. The mean age was 69 years (extremes 35 to 89s). Almost all patients (94%)
      were symptomatic (54% syncope and 30% dizziness and lipothymias). The main
      indication for definitive cardiac pacing was complete atrioventricular block of
      degenerative origin (83%). The mean time between indication and surgery was 8.2
      days, and only 4% of patients received temporary stimulation. The lack of
      financial support was the main reason for the delay in taking charge. During the
      study period, the two health centers received support in the form of stimulation
      equipment, a technical platform, and regular training and practical training.
      This collaboration made it possible to overcome the lack of material, human and
      financial resources. We recorded as complications a case of case exteriorization,
      two cases of benign local hematoma and two cases of probe displacement. The
      quality of life of the patients improved markedly, none of patients undergoing
      surgery remained symptomatic. CONCLUSION: The organization of cardiac stimulation
      in Burkina Faso is a reality. Efforts must be made to sustain the activity and
      strengthen collaboration with hospitals in the north.

PMID- 29050735
TI  - [Inferior myocardial infarction complicated by complete heart block and cardiac
      arrest following a gadolinium injection: A case of Kounis syndrome].
AB  - Kounis syndrome is an allergic acute coronary syndrome. It occurs on healthy or
      pathological arteries. Its complications, although often benign, can lead to
      cardiac arrest and death. Its triggering factors are multiple and include
      contrast products used in diagnostic imaging. We report the case of an 81 years
      old patient affected by hepatocellular carcinoma, who presented a type 2 Kounis
      syndrome with inferior myocardial infarction, complicated by cardiac arrest
      related to complete heart block following a gadoteric acid injection.

PMID- 29050737
TI  - [Lead-related infective endocarditis with massive vegetation causing severe
      functionnal tricuspid stenosis].
AB  - Lead-related infective endocarditis with negative hemocultures constitutes a
      severe condition potentially associated with a pejorative prognosis. It may
      induce a functional tricuspid stenosis caused by an important obstructive
      vegetation. We report the case of an 82 year-old woman in whom the lead-related
      endocarditis produced massive vegetation causing a severe functional tricuspid
      stenosis. We describe the medical history, diagnosis and treatment.

PMID- 29050736
TI  - [Complicated transcatheter aortic-valve endocarditis with abscess and
      pseudoaneurysm: Value of the ECG-gated multidetector computed tomography
      angiography].
AB  - A 80-year-old man was admitted to catheterization room for an acute infero
      lateral ST-elevation myocardial infarction (STEMI). Coronary angiography showed a
      thrombotic occlusion of the second left marginal branch, and normal other
      coronary arteries. The thrombo-embolic mechanism of the STEMI, and the infectious
      context in this patient who had had a transcatheter aortic valve implantation
      (TAVI) two months earlier, led us to suspect a bioprosthesis endocarditis. It was
      confirmed by transthoracic and transoesophageal echocardiography, which showed an
      aortic-mitral curtain abscess and aortic bioprosthesis vegetations, associated to
      Enterococcus faecalis bacteriemia. In order to specify the diagnosis, an ECG
      gated multidetector CT angiography (MDCTA) had been performed. Additionally to
      echocardiographic findings, MDCTA showed a pseudo-aneurysm, sized 20 to 22mm,
      beginning from the outflow tract of the left ventricle to end on the antero
      lateral face of the aorta. The patient was referred for emergency aortic
      bioprosthesis removal and replacement. Through this case, MDCTA showed its
      importance for the diagnosis and the prognostic evaluation of cardiac prosthesis
      endocarditis. MDCTA provided additional informations that echocardiography could
      not detect, because of artifacts caused by the prosthetic material and
      calcifications, frequent in elderly patients with comorbidities.

PMID- 29050738
TI  - [TIMMA: Ultrasonographic scale of carotid atherosclerosis by vascular
      neurologists].
AB  - BACKGROUND: Carotid atherosclerosis is a powerful predictive factor of vascular
      risk at the individual patient level. Ultrasonography is a reference technique
      for the evaluation of this condition. However, its use in common practice remains
      difficult due to a lack of standardization and inter-operator variability. We
      present a new and simple technique for the assessment of carotid atherosclerosis;
      and evaluate the ability of vascular neurologists to obtain results consistent
      with those of an expert in vascular ultrasound. MATERIAL AND METHODS: The TIMMA
      scale is an acronym for the five classes of carotid atherosclerosis in French,
      VIMMA in English: very important, important, moderate, minimal and absent.
      Combined, the first two classes make up the group "significant atheroma" and the
      last three classes make up the group "no significant atheroma". This scale was
      evaluated in 38 patients (76 carotid arteries) suffering from ischemic stroke or
      transient ischemic attack by five operators who are competent in carotid
      echocardiography: one TIMMA-trained (40 hours of training) vascular neurologist
      physician (VNP), three VNPs informed on the measurement method (1 hour of
      information) and one specialized vascular physician (SVP) who was considered to
      be the reference examiner. We evaluated the concordance between the VNPs and the
      SVP in classifying patients, firstly into the significant or not atheroma group
      and, secondly, into the five TIMMA classes. RESULTS: The evaluation of the two
      group clustering scale found a concordance between the informed VNPs and the SVP
      on 76 carotid arteries of 86% (kappa=0.7) and between the trained VNP and the SVP
      on 58 carotid arteries of 90% (kappa=0.8). The positive and negative predictive
      values for significant atheroma diagnosis were 100% and 81%, respectively, for
      the informed VNPs, and 100% and 80% for the trained VNP. The evaluation of the
      Five-Class Scale showed a concordance between the informed VNPs and the SVP of
      46% (kappa=0.3), and between the trained VNP and the SVP of 74% (kappa=0.7).
      CONCLUSION: TIMMA allows VNPs who are competent in carotid ultrasonography to
      reproducibly identify subjects with significant carotid atheroma. The
      contribution of this scale to the determination of cardiovascular risk should be
      evaluated.

PMID- 29050739
TI  - [Evaluation about patient's knowledge on their direct oral anticoagulants
      treatment].
AB  - AIM OF THE STUDY: Patient's knowledge about their treatment is poor, generally
      speaking. New oral anticoagulants are easier to use compared to antivitamin K,
      and they are going to increase. This simplification can underestimate their high
      potential risk. We have assessed patient's knowledge about their direct oral
      anticoagulants. METHODS: It was a quantitative, observational, multicentric,
      prospective study, on 50 patients on Direct Oral Anticoagulants. They have been
      included from November 2015 to February 2017, in Ile-de-France. They were needed
      to be aged more than 18years old, whatever was: the reason of this treatment, the
      beginning of it, the molecule, the existence or not of antivitamin K before.
      Their knowledge was assessed by a survey, realised by a unique investigator. The
      primary outcome was to reach more than 80% good answers to the survey. Secondary
      outcomes were to identify factors than can influence knowledge. RESULTS: Among
      fifty patients, nine (18%) reached a goal over or equal to 80%. They knew the
      name of their medicament in 58% of cases, and the indication in 72% of cases.
      They could identify hemorragic signs in more than 70% of cases. In case of
      hemorragic sign, 94% of them were going to see a doctor. Thrombosis signs were
      less knew. None of the factors, excepted their profession, was different in the
      two populations (P=0,01). CONCLUSION: This study showed the few rate of patient
      knowing their oral anticoagulants treatment perfectly, and their need to improve
      it. It could make professional healthcare aware to this problematic.

PMID- 29050740
TI  - [Asymptomatic Brugada syndrome: From diagnosis to treatment].
AB  - Brugada syndrome management may be a difficult question. This article reviews
      diagnosis, prognosis evaluation, current and investigated treatments.

PMID- 29050741
TI  - [Diagnosis of arrhythmias on memories of pacemakers and defibrillators: Practical
      management].
AB  - Pacemakers and defibrillators have holter capabilities that can record episodes
      of arrhythmias. Different studies evaluated the effect on the risk of strokes of
      different durations of arrhythmias. The question of the management of patients
      depending on the duration of the arrhythmia episode is addressed in this article
      depending on the duration of the episode and the arrhythmia burden.

PMID- 29050742
TI  - [Sudden cardiac death and anomalous connections of the coronary arteries: What is
      known and what is unknown?]
AB  - Some anomalous connections of the coronary arteries may be associated with a risk
      of sudden cardiac death. In opposite with others cardiac diseases at risk of
      sudden cardiac death, the relationship between these congenital abnormalities and
      the risk of sudden cardiac death are not well understood. A correction of the
      anomaly is generally indicated after an aborted sudden cardiac death. Primary
      prevention strategy after the discovery of an anomaly at risk is debated. Even if
      the absolute risk of sudden death is very low, a pre-participation screening in
      young athletes may be discussed due to a non-rare incidence.

PMID- 29050743
TI  - [Abdominal aorta aneurysms discovered in cardiac rehabilitation].
AB  - We reported two cases of unusual discovery of asymptomatic surgical abdominal
      aortic aneurysm (AAA) after a coronary artery bypass graft and a valve surgery.
      Attending cardiac rehabilitation, the patients were transferred for prompt
      surgery. Beyond these observations, it is of great importance that screening of
      AAA could be done during echocardiography.

PMID- 29050744
TI  - [Stress dobutamine echocardiography or resting strain rate imaging to unveil an
      early symptomatic diabetic cardiomyopathy?]
AB  - Diabetes mellitus has been associated with changes in the structure and function
      of the myocardium manifesting in the early stages of the disease as subtle
      systolic and diastolic dysfunction; myocardial strain imaging has recently been
      favored over dobutamine stress echocardiography for early detection of diabetic
      cardiomyopathy. We report a case of an elderly diabetic patient presenting with
      pulmonary edema in whom at rest echocardiographic parameters including strain
      rate were all within normal range, while dobutamine stress echocardiography
      induced a deep systolic deterioration unmasking an early-stage diabetic
      cardiomyopathy.

PMID- 29050746
TI  - From the Editor.

PMID- 29050745
TI  - A spectrum of retinal vasculature measures and coronary artery disease.
AB  - BACKGROUND AND AIMS: We aimed to comprehensively describe a spectrum of retinal
      vessel measures including fractal dimension (Df) and their associations with
      indices of coronary artery disease (CAD) extent and severity, as well as
      hypertension and diabetes. METHODS: The Australian Heart Eye Study (AHES) is an
      observational study that surveyed 1680 participants presenting to a tertiary
      referral hospital for the evaluation of potential CAD by coronary angiography. A
      range of newer retinal vessel geometric measures (Df, curvature tortuosity, and
      branching angle) were quantified from retinal photographs using semi-automated
      software, the Singapore 'I' Vessel Assessment (SIVA) tool. A combined retinal
      score was constructed, aiming to assess the joint effect of multiple retinal
      vessel parameters on CAD, comprising of those variables that were most strongly
      significant in multivariate analysis - Df, arteriolar curvature tortuosity, and
      retinal arteriolar calibre. CAD was objectively quantified using a range of
      measures obtained from coronary angiography. RESULTS: A total of 1187
      participants had complete data on retinal vessel measurements and coronary vessel
      evaluation. Retinal vascular Df and curvature tortuosity decreased with
      increasing age; women had significantly lower Df than men (p<0.003). Straighter
      retinal vessels were associated with CAD extent and Gensini scores in
      multivariable analysis (p<0.02). Accounting for media opacity by sub-group
      analysis in pseudophakic patients, the combined retinal score was associated with
      stenosis greater than 50% in any coronary artery segment (vessel score) and
      obstructive coronary stenosis in all three main coronary arteries (segment score)
      (p = 0.01). Lower Df and narrower arteriolar branching angle were associated with
      CAD vessel score (p<0.03). In sex-stratified multivariate analyses, straighter
      arterioles were associated with greater odds of CAD in men, and narrower venular
      branching angle was associated with CAD in women. CONCLUSIONS: A range of retinal
      vessel measures were associated with CAD extent and severity. A sparser retinal
      microvascular network (smaller Df) was associated with older age and female
      gender. After accounting for the impact of media opacity, retinal vessel measures
      were associated with more diffuse and severe CAD.

PMID- 29050747
TI  - Soluble (pro)renin receptor in preeclampsia and diabetic pregnancies.
AB  - Women with preexisting or gestational diabetes mellitus have an increased risk
      for developing preeclampsia. Diabetes and pregnancy are both characterized by
      very high prorenin levels and renin-angiotensin system activation. Prorenin bound
      to the (pro)renin receptor has enzymatic activity. We hypothesized that soluble
      (pro)renin receptor levels are elevated in high-risk pregnancies. Third trimester
      maternal blood samples from complicated pregnancies (n = 165), (preeclampsia [n =
      76], diabetes mellitus [type I diabetes, n = 35; type II diabetes, n = 11;
      gestational diabetes mellitus, n = 43]), and healthy pregnancies (n = 49) were
      analyzed for prorenin, renin, and soluble (pro)renin receptor. There were no
      significant differences in prorenin or renin levels between the study groups in a
      multivariate model. In the group of women with gestational diabetes, soluble
      (pro)renin receptor concentrations were significantly higher compared with
      healthy pregnancies or preeclampsia. Soluble (pro)renin receptor did not
      correlate with renin or prorenin levels for any of the study groups. Our results
      show that soluble (pro)renin receptor is dysregulated in pregnancies affected by
      diabetes mellitus, but not in preeclampsia. Alterations in circulating soluble
      (pro)renin receptor are unrelated to renin/prorenin in pregnancy, but may be of
      pathophysiological relevance in diabetic pregnancies in a renin-angiotensin
      system-independent manner.

PMID- 29050748
TI  - Pediatric Kikuchi-Fujimoto disease: A clinicopathologic study and the therapeutic
      effects of hydroxychloroquine.
AB  - BACKGROUND: To investigate the clinical features of Kikuchi-Fujimoto disease
      (KFD) in children, and place an emphasis on the therapeutic effects of
      hydroxychloroquine as monotherapy. METHODS: We retrospectively reviewed the
      medical records of all children diagnosed with KFD during the period January 1992
      to September 2016 at a tertiary medical center in Taiwan. RESULTS: 40 patients
      were histopathologically confirmed as KFD, and the mean age of the patients was
      13.9 +/- 3.1 years. The male to female ratio was 1:1. The lymph node involvements
      were often cervical (95%) with features of unilateral predisposition (75%),
      polyadenopathy (84.4%) and tenderness (56.3%). Fever, cough, rhinorrhea, and
      tonsillitis were other common presentations. Laboratory findings included
      leukopenia (56.5%), monocytosis (63.6%), with positive results of EB-VCA IgG
      (88.9%), EB-VCA IgM (22.2%), EBEA IgG (22.2%) and EBNA IgG (88.9%). The
      univariate analyses of prolonged fever with lymphopenia, monocytosis,
      thrombocytopenia and necrotizing type in histopathology were disclosed as
      statistically significant (P < 0.05). Corticosteroids and hydroxychloroquine were
      administered in 15.6% of patients respectively, along with symptomatic treatments
      for the rest. Recurrence occurred in 13.0% of patients without corticosteroids or
      hydroxychloroquine treatment. There were neither recurrences nor relevant major
      adverse effects in all the five KFD cases treated with hydroxychloroquine.
      CONCLUSION: KFD should be suspected in children with febrile cervical
      lymphadenopathy, especially when concomitant with leukopenia and monocytosis.
      Lymphopenia, monocytosis, thrombocytopenia and necrotizing type in histopathology
      are reliable predictors for prolonged fever. Hydroxychloroquine may be an
      alternative choice to corticosteroids for its favorable effects and safety.

PMID- 29050750
TI  - Reply to Dr Moritz.

PMID- 29050749
TI  - Impact of reduced tigecycline susceptibility on clinical outcomes of
      Acinetobacter bacteremia.
AB  - The higher 14-day mortality rate for patients with Acinetobacter bacteremia
      receiving tigecycline appropriately compared to other appropriate antibiotics
      (36.4% versus 14.2%, P = 0.028) was due to the poor effect of tigecycline for
      isolates with a minimum inhibitory concentration of 2 MUg/mL (63.6% of 11 versus
      14.2% of 127, P = 0.001).

PMID- 29050752
TI  - Maternal Substance Use Disorders and Infant Outcomes in the First Year of Life
      among Massachusetts Singletons, 2003-2010.
AB  - OBJECTIVE: To determine the association of maternal substance use disorders
      (SUDs) during pregnancy with adverse neonatal outcomes and infant hospital re
      admissions, observational stays, and emergency department utilization in the
      first year of life. STUDY DESIGN: We analyzed 2 linked statewide datasets from
      2002 to 2010: the Massachusetts Pregnancy to Early Life Longitudinal data system
      and the Massachusetts Bureau of Substance Abuse Services Management Information
      System. Generalized estimating equations were used to assess the association of
      maternal SUDs and neonatal outcomes and infant hospital-based care in the first
      year of life, controlling for maternal and infant characteristics. RESULTS:
      Maternal SUDs increased from 19.4 per 1000 live births in 2003 to 31.1 per 1000
      live births in 2009. In the adjusted analysis, exposed neonates were more likely
      to be born preterm (aOR 1.85; 95% CI 1.75-1.96) and low birthweight (aOR 1.94;
      95% CI 1.80-2.09). After controlling for maternal characteristics and preterm
      birth, SUD-exposed neonates were more likely to have intrauterine growth
      restriction, cardiac, respiratory, neurologic, infectious, hematologic, and
      feeding/nutrition problems, prolonged hospital stay, and higher mortality (aOR
      range 1.26-3.80). Exposed infants were more likely to be rehospitalized (aOR
      1.10; 95% CI 1.04-1.17) but less likely to have an observational stay (aOR 0.90;
      95% CI 0.82-0.99) or use the emergency department (aOR 0.87; 95% CI 0.83-0.90) in
      the first year of life. CONCLUSIONS: Infants born to mothers with SUD are at
      higher risk for adverse health outcomes in the perinatal period and are also more
      likely to be rehospitalized in the first year of life.

PMID- 29050751
TI  - Fibrosis-Related Gene Expression in Single Ventricle Heart Disease.
AB  - OBJECTIVE: To evaluate fibrosis and fibrosis-related gene expression in the
      myocardium of pediatric subjects with single ventricle with right ventricular
      failure. STUDY DESIGN: Real-time quantitative polymerase chain reaction was
      performed on explanted right ventricular myocardium of pediatric subjects with
      single ventricle disease and controls with nonfailing heart disease. Subjects
      were divided into 3 groups: single ventricle failing (right ventricular failure
      before or after stage I palliation), single ventricle nonfailing (infants listed
      for primary transplantation with normal right ventricular function), and stage
      III (Fontan or right ventricular failure after stage III). To evaluate subjects
      of similar age and right ventricular volume loading, single ventricle disease
      with failure was compared with single ventricle without failure and stage III was
      compared with nonfailing right ventricular disease. Histologic fibrosis was
      assessed in all hearts. Mann-Whitney tests were performed to identify differences
      in gene expression. RESULTS: Collagen (Col1alpha, Col3) expression is decreased
      in single ventricle congenital heart disease with failure compared with
      nonfailing single ventricle congenital heart disease (P = .019 and P = .035,
      respectively), and is equivalent in stage III compared with nonfailing right
      ventricular heart disease. Tissue inhibitors of metalloproteinase (TIMP-1, TIMP
      3, and TIMP-4) are downregulated in stage III compared with nonfailing right
      ventricular heart disease (P = .0047, P = .013 and P = .013, respectively).
      Matrix metalloproteinases (MMP-2, MMP-9) are similar between nonfailing single
      ventricular heart disease and failing single ventricular heart disease, and
      between stage III heart disease and nonfailing right ventricular heart disease.
      There is no difference in the prevalence of right ventricular fibrosis by
      histology in subjects with single ventricular failure heart disease with right
      ventricular failure (18%) compared with those with normal right ventricular
      function (38%). CONCLUSIONS: Fibrosis is not a primary contributor to right
      ventricular failure in infants and young children with single ventricular heart
      disease. Additional studies are required to understand whether antifibrotic
      therapies are beneficial in this population.

PMID- 29050753
TI  - Outcome of spray cryotherapy plus functional endoscopic sinus surgery on
      management of healing in nasal polyposis.
AB  - BACKGROUND: Nasal Polyposis is a benign tumor in nasal or paranasal mucosa, which
      confronts difficulties in management of healing after treatments with surgery.
      The aim of this study was to evaluate the effects of Spray Cryotherapy (SCT) on
      management of healing in patients with nasal polyposis who undergone functional
      endoscopic sinus surgery. METHODS: In this prospective, clinical trial study, we
      investigated on 40 patients with nasal polyposis that had indication for
      functional endoscopic sinus surgery. Patients were divided randomly into two
      parallel group; cryotherapy (with SCT) and placebo (without SCT). Evaluation of
      healing after surgery was evaluated with Lund-Mackay and The Sino-nasal outcome
      test (SNOT-22)-22 scores. RESULT: Postoperatively, Lund-Mackay and SNOT-22 scores
      were significantly decreased in both groups, however these scores were
      significantly lower in cryotherapy group in comparison with placebo group. Also
      there were no reported serious side effects in both groups. CONCLUSION: In this
      paper, we concluded that usage of SCT is an effective and safe method on
      management of healing and develops recovery rates in patients with nasal
      polyposis undergoing functional endoscopic sinus surgery.

PMID- 29050754
TI  - Core Needle Biopsy Versus Fine Needle Aspiration Biopsy in Diagnosing Lung
      Cancer.

PMID- 29050755
TI  - Applied multiplex allele specific PCR to detect second-line drug resistance among
      multidrug-resistant tuberculosis in China.
AB  - Rapid detection of resistance to the second-line drugs is essential for early
      initiation of appropriate anti-tubercular treatment regimen among multi-drug
      tuberculosis (MDR-TB). In this study, we applied a multiplex allele-specific PCR
      (MAS-PCR) to identify the mutations on codons 90 and 94 of gyrA and nucleotide
      1401 of rrs for detecting ofloxacin (OFX) and kanamycin (KAN) resistance in 139
      MDR-TB isolates from China. Using the traditional phenotypic method as the
      reference, MAS-PCR detected resistance to OFX and KAN with sensitivities of 67.3%
      and 76.5%, respectively, and specificities of 100.0%. Therefore, MAS-PCR assays
      can be used for rapid detection of second-line drug resistance among MDR-TB in
      China, enabling early administration of appropriate treatment regimens to the
      affected MDR-TB patients.

PMID- 29050756
TI  - Clinical significance of serum CA-125, CA19-9 and CEA in pulmonary tuberculosis
      with and without type 2 diabetes.

PMID- 29050757
TI  - Ionophore A23187 shows anti-tuberculosis activity and synergy with tebipenem.
AB  - The objective of this study was to find molecules with anti-mycobacterial
      activity from a natural compounds library, investigate their mechanisms of
      resistance, and assess their synergy with antibiotics. We screened a library of
      2582 natural compounds with Mycobacterium aurum with the aim of identifying
      molecules with anti-mycobacterial activity. The hits with the lowest MICs in M.
      aurum were also tested for their antimicrobial activity in other mycobacterial
      species including M. tuberculosis complex strains. The chequerboard titration
      assay was chosen for determining drug interactions in vitro. Spontaneous
      resistant mutants were isolated and their whole genome sequences compared to wild
      type and resistant mutants to identify resistance mechanisms. We found that
      ionophores show anti-mycobacterial activity in vitro. Resistance mechanism to
      ionophores is mediated by the MmpL5-MmpS5 transporter overexpression. Ionophore
      A23187 enhanced beta-lactam activity in M. tuberculosis infected macrophage. It
      will help in the investigation of new drug combinations against bacterial
      infections including tuberculosis.

PMID- 29050758
TI  - Identification of mycobacterial bacterioferritin B for immune screening of
      tuberculosis and latent tuberculosis infection.
AB  - OBJECTIVES: It remains necessary and urgent to search for novel mycobacterial
      antigens to increase the sensitivity and specificity for tuberculosis (TB)
      diagnosis and latent TB infection (LTBI) screening. Antigens capable of inducing
      strong immune responses during Mycobacterium tuberculosis (M.tb) infection would
      be good candidates. METHODS: Cellular responses specific to M.tb derived
      bacterioferritin B (BfrB) were assessed by IFN-gamma ELISPOT in three human
      cohorts, including healthy controls (HCs), LTBI population and pulmonary TB (PTB)
      patients. Its significance in TB diagnosis and LTBI identification was further
      analyzed. RESULTS: BfrB-specific IFN-gamma responses in PTB and LTBI groups were
      significantly higher than that in HCs. However, BfrB-specific IFN-gamma release
      was not as strong as that to ESAT-6 or CFP-10 in PTB patients whereas comparable
      in LTBI cohort with possible complementary properties to ESAT-6 or CFP-10. More
      interestingly, there were a considerable number of HCs with high BfrB-specific
      cellular responses. When HCs with high BfrB-specific cellular responses were
      subgrouped into ESAT-6/CFP-10hi (SFUs = 3, 4, 5) and ESAT-6/CFP-10lo (SFUs < 3)
      groups, those who belonged to ESAT-6/CFP-10hi group exhibited higher PPD
      responsiveness than ESAT-6/CFP-10lo group. CONCLUSIONS: PTB and LTBI groups
      exhibit higher BfrB-specific IFN-gamma responses than HCs. Although BfrB is not
      as immunodominant as ESAT-6/CFP-10 during acute M.tb infection, comparable BfrB
      specific cellular immune responses are observed in LTBI population with the
      potential to increase the sensitivity for LTBI screening. Moreover, strong BfrB
      specific IFN-gamma release in the healthy cohort is probably cautionary in
      identifying leaky LTBI from HCs. BfrB might thus be considered as an additional
      biomarker antigen for LTBI identification.

PMID- 29050759
TI  - Modeling tuberculosis pathogenesis through ex vivo lung tissue infection.
AB  - Tuberculosis (TB) is one of the top 10 causes of death worldwide. Several in
      vitro and in vivo experimental models have been used to study TB pathogenesis and
      induction of immune response during Mycobacterium tuberculosis infection.
      Precision cut lung tissue slices (PCLTS) is an experimental model, in which all
      the usual cell types of the organ are found, the tissue architecture and the
      interactions amongst the different cells are maintained. PCLTS in good
      physiological conditions, monitored by MTT assay and histology, were infected
      with either virulent Mycobacterium tuberculosis strain H37Rv or the TB vaccine
      strain Mycobacterium bovis BCG. Histological analysis showed that bacilli
      infecting lung tissue slices were observed in the alveolar septa, alveolar light
      spaces, near to type II pneumocytes, and inside macrophages. Mycobacterial
      infection of PCLTS induced TNF-alpha production, which is consistent with
      previous M. tuberculosis in vitro and in vivo studies. This is the first report
      of using PCLTS as a system to study M. tuberculosis infection. The PCLTS model
      provides a useful tool to evaluate the innate immune responses and other aspects
      during the early stages of mycobacterial infection.

PMID- 29050760
TI  - MmpS5/MmpL5 as an efflux pump in Mycobacterium species.
AB  - Tuberculosis remains an important cause of morbidity and mortality throughout the
      world, amplified by the expansion of antibiotic resistance. Increasing active
      efflux of the antibiotic is one of the several strategies used by bacteria to
      resist to antibiotics. After showing the importance of the RND superfamily of
      efflux pumps in drug resistance, this review focuses on the protein MmpL5, a
      transmembrane transporter of Mycobacterium. These exporters should be involved in
      the variety of roles in bacterial cells, including expelling various drugs. The
      mutation in the transcriptional regulator, linked to the upregulation of MmpL5
      can lead to resistance of antibiotics. The study of these mechanisms should be
      considered in order to improve the treatment of tuberculosis.

PMID- 29050761
TI  - Mechanisms of resistance against NITD-916, a direct inhibitor of Mycobacterium
      tuberculosis InhA.
AB  - Isoniazid inhibits Mycobacterium tuberculosis InhA and is a key component of drug
      regimens that treat tuberculosis. However, the high rate of resistance against
      isoniazid is a contributing factor to the emergence of multi-drug resistance
      strains of M. tuberculosis. The 4-hydroxy-2-pyridine NITD-916 is a direct
      inhibitor of M. tuberculosis InhA that has comparable efficacy to isoniazid in
      mouse models of TB infection but a lower frequency of resistance. To characterize
      resistance mechanisms against NITD-916 we isolated resistant mutants in H37Rv
      (Euro-American lineage) and HN878 (East-Asian lineage) strains of M.
      tuberculosis. The resistance frequency was similar in both strains. Mutations
      were identified in residues within or near to the active of InhA or in the
      fabG1inhA promoter region. All mutants were resistant to NITD-916 but were not
      cross resistant to isoniazid, despite homology to SNPs identified in isoniazid
      resistant clinical isolates.

PMID- 29050762
TI  - Whole genome sequencing for the management of drug-resistant TB in low income
      high TB burden settings: Challenges and implications.
AB  - Drug-resistant tuberculosis is emerging as a major global health challenge,
      fuelled by a limited formulary and reduced ability to timeously diagnose
      resistance. Furthermore, poorly managed drug-resistant tuberculosis is
      complicated by poor treatment outcomes and high rates of morbidity and mortality.
      A rapid diagnosis together with individualized management are essential in order
      to limit disease and curtail transmission. Recently, the feasibility of Whole
      Genome Sequencing (WGS) technology for the routine diagnosis and drug
      susceptibility testing of Mycobacterium Tuberculosis in a high income, low
      tuberculosis burden setting, was demonstrated. However, the use of WGS in low
      income settings, with the highest burden of disease, has not been evaluated. This
      viewpoint highlights the challenges and implications associated with the use of
      Whole Genome Sequencing for the diagnosis and management of drug-resistant
      tuberculosis in such settings.

PMID- 29050763
TI  - Variants of katG, inhA and nat genes are not associated with mutations in efflux
      pump genes (mmpL3 and mmpL7) in isoniazid-resistant clinical isolates of
      Mycobacterium tuberculosis from India.
AB  - To understand the impact of efflux pump genes such as mmpL3 and mmpL7 on
      isoniazid (INH) resistance and to correlate with presence or absence of mutations
      in essential genes of INH resistance (katG, inhA, and nat) in clinical isolates
      of Mycobacterium tuberculosis (M. tuberculosis). One hundred (75 resistant and 25
      sensitive) clinical isolates of M. tuberculosis from India were selected for the
      study. The presence of mutations in specific regions of katG, inhA, and nat,
      efflux pump genes (mmpL3 and mmpL7) associated with INH resistance were analyzed
      using multiplex allele-specific polymerase chain reaction (MAS-PCR) and DNA
      sequencing methods, respectively. Substitution mutation AGC-ACC at codon 315 of
      the katG gene was detected in 65% of resistant isolates. Mutation (C-T at
      nucleotide position 15) in the inhA promoter region was seen in 22% of resistant
      isolates. Silent mutation (GGA to GGG) at codon 207 in the nat gene was found in
      three resistant isolates. No mutations were found in either of the efflux genes
      (mmpL3 and mmpL7) in any of the isolates. Of the 75 resistant isolates analyzed,
      74% had mutation in katG and inhA genes. Thus, this report suggests that the role
      of mmpL3, mmpL7 and nat genes in INH resistance should not be overestimated in
      comparison to the primary contribution by katG and inhA in clinical isolates of
      M. tuberculosis. Further, this concise report is the first of its kind to our
      knowledge, to show the influence of efflux genes on INH resistance in relation to
      katG and inhA in clinical isolates of M. tuberculosis.

PMID- 29050764
TI  - Pharmacokinetic studies of a three-component complex that repurposes the front
      line antibiotic isoniazid against Mycobacterium tuberculosis.
AB  - The frontline tuberculosis (Tb) antibiotic isoniazid has been repurposed using a
      three component complex aimed at increasing the delivery efficiency and adding
      new avenues to its mechanism of action. This study focuses on pharmacokinetic
      studies of the isoniazid-sucrose-copper (II)-PEG-3350 complex. The assays include
      the Plasma Protein Binding Assay (85.8%), Caco-2 Permeability Assay (B->APapp,
      0.13 * 10-6 cm/s), Cytochrome P450 Inhibition Assay (i.e. CYP2B6, IC50 = 7.26
      MUM), In vitro microsomal Stability Assay (t1/2 NADPH-Dependent > 240 min), and
      HepG2 Cytotoxicity (no toxicity). The National Cancer Institute's 60 cell line
      panel is used to measure activity against cancer cells. The percent growth values
      averaged over all 60 cell lines indicates the complex has no anti-cancer
      activity, which also suggests a lack of general toxicity. It also provides data
      for the complexes specificity against Mycobacterium tuberculosis.

PMID- 29050765
TI  - Alveolar macrophages from tuberculosis patients display an altered inflammatory
      gene expression profile.
AB  - Alveolar macrophages (AMs) are major targets of Mycobacterium tuberculosis (Mtb)
      infection, critical during the progression of active tuberculosis (TB). The
      complex immunopathology of TB generates diverse microenvironments in the lung,
      which shape immune responses by AMs. In the current study, we perform whole
      genome microarray transcriptional profiling on RNA isolated from AMs from TB
      patients (AMsTB) compared to AMs from control subjects (AMsCT) using
      bronchoalveolar lavage (BAL). Our hypothesis was that systemic effects on the
      local lung microenvironment during TB affect the transcriptional response of
      AMsTB. We found a unique gene expression profile of 51 genes, including up
      regulated CHIT1, CHI3L1, CCL5, CCL22, CCL8, CXCL9, MMP9, MMP7 and MMP12,
      associated with a robust pro-inflammatory response, cell recruitment and tissue
      damage, and genes of the cyclin family (CCND1, CCND2, and CCNA1) associated with
      cell proliferation. These expression profiles may account for the inflammatory
      condition in the lungs of TB patients. CXCL5, IL1B, CAMP, and TGFB1 were down
      regulated, suggesting an altered control of Mtb infection. Also, MARCO and
      COLEC12, affecting phagocytosis, and CES1, associated with an increase in free
      cholesterol, were down-regulated. The observed changes in mRNA expression
      profiles may partially account for the inability of AMsTB to effectively control
      Mtb infection, suggesting that a balanced control of pro- and anti-inflammatory
      immune responses is crucial for infection control.

PMID- 29050766
TI  - Mixed infections in tuberculosis: The missing part in a puzzle.
AB  - The mixed strains infection phenomenon is a major problem posing serious
      challenges in control of tuberculosis (TB). In patients with mixed infection,
      several different strains of Mycobacterium tuberculosis can be isolated
      simultaneously. Although different genotyping methods and various molecular
      approaches can be employed for detection of mixed infection in clinical samples,
      the MIRU-VNTR technique is more sensitive with higher discriminative power than
      many widely used techniques. Furthermore, the recent introduction of whole genome
      sequencing (WGS) promises to reveal more details about mixed infection with high
      resolution. WGS has been used for detection of mixed infection with high
      sensitivity and discriminatory, but the technology is currently limited to
      developed countries. Mixed infection may involve strains with different
      susceptibility patterns, which may alter the treatment outcome. In this report,
      we review the current concepts of mixed strains infection and also infection
      involving strains with a different susceptibility pattern in TB. We evaluate the
      importance of identifying mixed infection for diagnosis as well as treatment and
      highlight the accuracy and clinical utility of direct genotyping of clinical
      specimens.

PMID- 29050767
TI  - CISH controls bacterial burden early after infection with Mycobacterium
      tuberculosis in mice.
AB  - CISH gene has been associated with increased susceptibility to human
      tuberculosis. We found that cish-/- mice had higher M. tuberculosis load in
      spleens and lungs up to 2.5 weeks after infection but not later compared to
      controls. Cish mRNA levels were increased in lungs at early and late time points
      after M. tuberculosis infection. In relation, the titers of inos and tnf mRNA in
      lungs were reduced early after infection of cish-/- mice. The transfer of cish-/-
      and control T cells conferred rag1-/- mice similar protection to infection with
      M. tuberculosis. Macrophages showed increased cish mRNA levels after M.
      tuberculosis infection in vitro. However, mycobacterial uptake and growth in cish
      /- and control macrophages was similar. Thus, we here show that CISH mediates
      control of M. tuberculosis in mice early after infection via regulation of innate
      immune mechanisms.

PMID- 29050768
TI  - Single nucleotide polymorphisms in efflux pumps genes in extensively drug
      resistant Mycobacterium tuberculosis isolates from Pakistan.
AB  - It is challenging to understand mechanisms of drug resistance in Mycobacterium
      tuberculosis (MTB) due to the large variability in resistance associated genes.
      Efflux pump genes contribute to drug resistance and thus add to this complexity.
      Efflux pump gene protein superfamilies have been characterized by genome analysis
      of drug resistant strains and through in vitro transcriptional studies. However,
      there is limited information regarding efflux pump genes in extensively drug
      resistant (XDR) tuberculosis (TB) isolates. Whole genome sequencing (WGS) based
      analysis of 37 extensively drug resistant (XDR) and five drug sensitive (DS) MTB
      clinical isolates was performed. Single nucleotide polymorphisms (SNPs) in efflux
      pump genes Rv0194, Rv1217, Rv1218, drrA, drrB, Rv1258, Rv1634, Rv2688, Rv1273,
      Rv1819, Rv1458, Rv1877 and Rv1250 were determined in the clinical isolates as
      compared with the H37Rv reference strain. Allele frequencies of SNPs identified
      in XDR strains were compared with DS strains. Gene expression of Rv0194, Rv2688,
      Rv1634, drrA and drrB was determined in XDR -TB isolates (n = 9), DS-TB strains
      (n = 4) and H37Rv. We identified SNPs in XDR-TB isolates which were either unique
      or present at very low frequencies in DS strains; Rv0194 G170V; Rv1217 L151R;
      Rv1258 P369T and G391R; Rv1273 S118G and I175T; Rv1877 I534T; Rv1250 V318X/A and
      S333A, and Rv2688 P156T. The expression of Rv2688 and drrB was found to be raised
      in XDR-TB as compared with DS-TB strains. We identified unique SNPs in efflux
      pump genes which may be associated with increased drug resistance in the
      isolates. Increased levels of Rv2688 and drrB efflux pump gene expression
      observed in XDR strains even in the absence of antibiotics suggests that these
      clinical isolates may be more refractory to treatment. Further studies are
      required to directly associate these mutations with increased resistance in MTB.

PMID- 29050769
TI  - Prevalence of Beijing and Haarlem genotypes among multidrug-resistant
      Mycobacterium tuberculosis in Iran: Systematic review and meta-analysis.
AB  - Antimicrobial drug resistance creates major problems in the control of
      tuberculosis (TB). Beijing and Haarlem genotypes of Mycobacterium tuberculosis
      are the prevalent genotypes responsible for multidrug resistant (MDR) TB
      worldwide. The aim of this study was to conduct a systematic review using meta
      analysis to indicate the prevalence of Beijing and Haarlem genotypes among MDR-TB
      cases in Iran. Data sources of current study were 311 original articles (2006
      2016) that were searched in several databases including Medline, Scopus, Embase,
      Cochrane library, and Iranian databases. Sixteen articles were selected for the
      prevalence of Beijing and Haarlem families among MDR-TB strains. Data were
      evaluated using meta-analysis and random effects models with the Meta-Analysis
      Software package Version 2.2 (Biostat, Englewood, NJ). Final investigation
      indicated 856 MDR samples in the 16 articles. Overall, the prevalence of Beijing
      and Haarlem genotypes among MDR-TB isolates in Iran was estimated to be 19.3%
      (95% CI, 13.1-27.5) and 18.7% (95% CI, 11.9-28.3) respectively. The studies
      conducted in northern Iran showing a significant association between Haarlem
      genotype and MDR is of particular concern. Certain refugee migration flows make
      this genotype of particular epidemiological and clinical concern because of its
      potential ability to endanger TB control programs in Iran.

PMID- 29050770
TI  - Genomic plasticity between human and mycobacterial DNA: A review.
AB  - Mycobacterium tuberculosis has a remarkable ability of long-term persistence
      despite vigorous host immunity and prolonged therapy. The bacteria persist in
      secure niches such as the mesenchymal stem cells in the bone marrow and
      reactivate the disease, leading to therapeutic failure. Many bacterial cells can
      remain latent within a diseased tissue so that their genetic material can be
      incorporated into the genetic material of the host tissue. This incorporated
      genetic material reproduces in a manner similar to that of cellular DNA. After
      the cell division, the incorporated gene is reproduced normally and distributed
      proportionately between the two progeny. This inherent adoption of long-term
      persistence and incorporating the bacterial genetic material into that of the
      host tissue remains and is considered imperative for microbial advancement and
      chemotherapeutic resistance; moreover, new evidence indicates that the bacteria
      might pass on genetic material to the host DNA sequence. Several studies focused
      on the survival mechanism of M. tuberculosis in the host immune system with the
      aim of helping the efforts to discover new drugs and vaccines against
      tuberculosis. This review explored the mechanisms through which this bacterium
      affects the expression of human genes. The first part of the review summarizes
      the current knowledge about the interactions between microbes and host
      microenvironment, with special reference to the M. tuberculosis neglected
      persistence in immune cells and stem cells. Then, we focused on how bacteria can
      affect human genes and their expression. Furthermore, we analyzed the literature
      base on the process of cell death during tuberculosis infection, giving
      particular emphasis to gene methylation as an inherited process in the
      neutralization of possibly injurious gene components in the genome. The final
      section discusses recent advances related to the M. tuberculosis interaction with
      host epigenetic circuitry.

PMID- 29050771
TI  - Host blood RNA signatures predict the outcome of tuberculosis treatment.
AB  - Biomarkers for tuberculosis treatment outcome will assist in guiding
      individualized treatment and evaluation of new therapies. To identify candidate
      biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment
      cohort was performed. Application of a validated transcriptional correlate of
      risk for TB revealed symmetry in host gene expression during progression from
      latent TB infection to active TB disease and resolution of disease during
      treatment, including return to control levels after drug therapy. The symmetry
      was also seen in a TB disease signature, constructed from the TB treatment
      cohort, that also functioned as a strong correlate of risk. Both signatures
      identified patients at risk of treatment failure 1-4 weeks after start of
      therapy. Further mining of the transcriptomes revealed an association between
      treatment failure and suppressed expression of mitochondrial genes before
      treatment initiation, leading to development of a novel baseline (pre-treatment)
      signature of treatment failure. These novel host responses to TB treatment were
      integrated into a five-gene real-time PCR-based signature that captures the
      clinically relevant responses to TB treatment and provides a convenient platform
      for stratifying patients according to their risk of treatment failure.
      Furthermore, this 5-gene signature is shown to correlate with the pulmonary
      inflammatory state (as measured by PET-CT) and can complement sputum-based Gene
      Xpert for patient stratification, providing a rapid and accurate alternative to
      current methods.

PMID- 29050772
TI  - CTL immunogenicity of Rv3615c antigen and diagnostic performances of an ESAT
      6/CFP-10/Rv3615c antigen cocktail for Mycobacterium tuberculosis infection.
AB  - T cell immune responses have played pivotal roles in host immune protection
      against Mycobacterium tuberculosis (MTB) infection. MTB specific antigen, Rv3615c
      (EspC), was identified to be as immunodominant as the well-known ESAT-6 and CFP
      10, and has brought promising expectations to more sensitive T-cell based
      diagnosis and vaccine development. However, limited knowledge about the
      immunogenicity and diagnostic values of this antigen has restricted its
      application in clinical practice. Herein, the Rv3615c antigen was identified as a
      robust CTL immunoantigen with broadly cross-human leucocyte antigen (HLA) allele
      recognized peptides which may contribute to the broad recognition of Rv3615c
      antigen among the population. A three-antigen-cocktail (3-Ag-cocktail) comprising
      of ESAT-6, CFP-10 and Rv3615c was investigated in a multicenter, randomized and
      double-blinded study to evaluate its clinical diagnostic performances. A
      significantly improved sensitivity was demonstrated against the 3-Ag-cocktail
      compared with that against ESAT-6 and CFP-10. Both responsive magnitude and
      sensitivity were significantly lower in patients concurrently suffering from
      cancer, indicating its restriction in diagnosis of immunocomprised patients. In
      conclusion, inclusion of the Rv3615c antigen with multiple HLA restricted CTL
      epitopes would benefit the T-cell based diagnosis of MTB infection.

PMID- 29050773
TI  - Detection of mycobacterial infection in non-human primates using the Xpert
      MTB/RIF molecular assay.
AB  - Tuberculosis is a major public health concern, and diagnostic strategies applied
      to animal populations are scarce. As part of ongoing efforts to control
      tuberculosis dissemination at our animal facility, two non-human primates (NHP,
      Saimiri sciureus) presenting cutaneous lesions were examined for mycobacterial
      infection. Both animals tested positive for acid-fast bacilli and Mycobacterium
      tuberculosis using a molecular assay (IS6110 PCR). Animals were euthanized and
      several samples were tested for M. tuberculosis using the Xpert MTB/RIF assay.
      Many samples were positive for M. tuberculosis and rifampicin resistance, and
      some produced mycobacterial growth. Oral swabs from cage mates were then tested
      with Xpert MTB/RIF, and the majority tested positive for M. tuberculosis and
      rifampicin resistance, and produced growth in culture. To our knowledge, this is
      the first report of multidrug-resistant mycobacterial infection in NHP.
      Additionally, our data shows that the Xpert MTB/RIF assay can be useful as a
      screening tool for tuberculosis infection in NHP.

PMID- 29050774
TI  - Whole genome sequencing of clinical strains of Mycobacterium tuberculosis from
      Mumbai, India: A potential tool for determining drug-resistance and strain
      lineage.
AB  - Amplification of drug resistance in Mycobacterium tuberculosis (M.tb) and its
      transmission are significant barriers in controlling tuberculosis (TB) globally.
      Diagnostic inaccuracies and delays impede appropriate drug administration, which
      exacerbates primary and secondary drug resistance. Increasing affordability of
      whole genome sequencing (WGS) and exhaustive cataloguing of drug resistance
      mutations is poised to revolutionise TB diagnostics and facilitate personalized
      drug therapy. However, application of WGS for diagnostics in high endemic areas
      is yet to be demonstrated. We report WGS of 74 clinical TB isolates from Mumbai,
      India, characterising genotypic drug resistance to first- and second-line anti-TB
      drugs. A concordance analysis between phenotypic and genotypic drug
      susceptibility of a subset of 29 isolates and the sensitivity of resistance
      prediction to the 4 drugs was calculated, viz. isoniazid-100%, rifampicin-100%,
      ethambutol-100% and streptomycin-85%. The whole genome based phylogeny showed
      almost equal proportion of East Asian (27/74) and Central Asian (25/74) strains.
      Interestingly we also found a clonal group of 9 isolates, of which 7 patients
      were found to be from the same geographical location and accessed the same health
      post. This provides the first evidence of epidemiological linkage for tracking TB
      transmission in India, an approach which has the potential to significantly
      improve chances of End-TB goals. Finally, the use of Mykrobe Predictor, as a
      standalone drug resistance and strain typing tool, requiring just few minutes to
      analyse raw WGS data into tabulated results, implies the rapid clinical
      applicability of WGS based TB diagnosis.

PMID- 29050775
TI  - Differential expression of long non-coding RNAs in patients with tuberculosis
      infection.
AB  - Tuberculosis (TB) remains a major worldwide health problem and has caused
      millions of deaths in the past few years. Current diagnostic methods, such as
      sputum smear microscopy and sputum culture, are time-consuming and cannot prevent
      the rapid spreading of TB during the diagnostic period. In this connection,
      detecting biomarkers specific to TB at molecular level in plasma of patients will
      provide a rapid means for diagnosis. In this study, we first evaluated the
      differential expression of the long non-coding RNAs (lncRNAs) in the plasma from
      patients with TB (TB positive), community acquired pneumonia (CAP) and healthy
      individuals (CG) using lncRNA microarray scanning. It was found that there were
      2116 specific lncRNAs differentially expressed in the TB positive samples (1102
      up-regulated and 1014 down-regulated), which accounted for 6.96% of total
      lncRNAs. Twelve differentially expressed lncRNAs discovered in microarray were
      subsequently validated by using real-time quantitative PCR (RT-qPCR). Two lncRNAs
      (ENST00000354432 and ENST00000427151) were further validated with more
      Tuberculosis samples. These results suggested the expression level of lncRNAs and
      the two validated lncRNAs in plasma could be the potential molecular biomarkers
      for the rapid diagnosis of Tuberculosis.

PMID- 29050776
TI  - Blood antimicrobial activity varies against different Mycobacterium spp.
AB  - In vitro analysis of mycobacterial pathogenicity or host susceptibility has
      traditionally relied on the infection of macrophages, the target cell of
      mycobacteria, despite difficulties reproducing their antimycobacterial activity.
      We have employed alternative models, namely whole blood and leukocytes in plasma,
      from QuantiFERON negative individuals, and performed infections with the
      pathogenic M. tuberculosis, the less pathogenic M. avium, M. kansasii and M.
      chelonae and the occasionally pathogenic M. gordonae and M. bovis. The
      anticoagulant used in blood extraction, heparin or EDTA, had a major influence in
      the outcome of the infection. Thus, while in the heparinized models a similar
      number of bacteria were enumerated in the inoculum and after seven days, in the
      presence of EDTA a killing effect was observed, despite the inhibitory effect of
      EDTA on cellular functions like the production of cytokines or reactive oxygen
      species (ROS). A special case was the rapidly growing mycobacteria M. chelonae,
      that multiplied in heparinized models but was eliminated in models with EDTA. We
      verified that EDTA is not responsible for the bactericidal effect, but acts as a
      bacteriostatic agent. Further work will determine whether blood derived models
      are a better alternative to the classical macrophage.

PMID- 29050777
TI  - Multiplex analysis of plasma cytokines/chemokines showing different immune
      responses in active TB patients, latent TB infection and healthy participants.
AB  - Interferon gamma release assays (IGRAs) have been widely used to diagnose
      Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate
      between active TB patients and latent TB infection (LTBI), and the sensitivity of
      IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in
      MTB antigen-stimulated and -unstimulated plasma samples to identify host
      biomarkers that are associated with active TB and MTB infection. Active TB
      patients, subjects with LTBI and healthy participants were recruited. Seventy-one
      soluble cytokines and chemokines were tested using Luminex liquid array-based
      multiplexed immunoassays. For the 71 examined factors, our results indicated that
      the unstimulated levels of IL-8 Nil, IP-10 Nil, MIP-1a Nil, and sIL-2Ra Nil and
      the antigen stimulated levels of IL-8 (Ag-Nil), VEGF (Ag-Nil), and MCP-3 (Ag-Nil)
      were potential biomarkers for differentiating between active TB and LTBI, with
      AUCs of 0.8, 0.86, 0.755, 0.845, 0.825, 0.812 and 0.75, respectively. The G-CSF
      (Ag-Nil), GM-CSF (Ag-Nil), IL-1a (Ag-Nil), IL-2 (Ag-Nil), IP-10 (Ag-Nil), BCA-1
      (Ag-Nil) and Eotaxin-1 (Ag-Nil) responses were significantly higher in patients
      with active TB and LTBI compared with healthy participants (p < 0.05), with AUCs
      of 0.922, 0.902, 0.908, 1.0, 0.937, 0.919 and 0.935, respectively. Our
      preliminary data suggest that unstimulated or stimulated levels of cytokines and
      chemokines could be used as host biomarkers for diagnosing active TB as well as
      additional biomarkers, except IFN-gamma, for MTB infection.

PMID- 29050778
TI  - The expressions and roles of different forms of IL-22 in Mycobacterium
      tuberculosis infection.
AB  - Despite evidence suggesting an anti-Mycobacterium tuberculosis effector function
      of CD4+ T cells that produce and retain IL-22 in macaques, the general role of IL
      22 in tuberculosis infection is still poorly characterized. To explore the immune
      mechanism in the pathogenesis of tuberculosis in humans, here we evaluated
      different forms of IL-22 in populations with different tuberculosis infection
      statuses. We enrolled 156 subjects including 49 patients with pulmonary
      tuberculosis, 27 patients with tuberculous pleurisy (TPE), 38 individuals with
      latent tuberculous infection (LTBI) and 42 healthy controls (HC). We found
      significantly higher IL-22 levels at the tuberculosis infection site than in the
      peripheral blood as well as higher antigen-specific IL-22 levels in the culture
      supernatant for patients with active tuberculosis than in healthy controls. The
      proportions of IL-22 + CD4+ T and IL-22 + CD8+ T cells in patients with active
      tuberculosis were significantly higher than those in the latent tuberculosis
      infection group and the healthy control group, based on intracellular cytokine
      staining. However, surprisingly, we found membrane-bound IL-22+ T cells,
      including CD4+ T cells and CD8+ T cells, by surface staining, especially in
      patients with active tuberculosis. Furthermore, the expression of membrane-bound
      IL-22 significantly decreased after drug therapy. In conclusion, our results
      suggest that IL-22 has various roles in tuberculosis immune responses. In
      particular, membrane-bound IL-22+ T cells may play important roles in the human
      immune response to Mycobacterium.

PMID- 29050779
TI  - Transcriptome landscape of long intergenic non-coding RNAs in endometrial cancer.
AB  - : Endometrial cancer is the most common gynecological malignancy in the developed
      world. It is the fifth most common cancer and accounts for 4.8% of all cancers in
      women. Long intergenic non-coding RNAs (lincRNAs), a subclass of long non-coding
      RNAs, are pervasively transcribed throughout the human genome. OBJECTIVE: LincRNA
      expression patterns in endometrial cancer compared to normal healthy tissue are
      poorly characterised. In this study, the lincRNA transcriptome of endometrial
      cancers and adjacent normal endometrium from the same patients was sequenced and
      compared with transcriptomes of other gynaecologic malignancies including ovarian
      and cervical cancers. METHODS: RNA was isolated from malignant and adjacent non
      affected endometrial tissue from 6 patients with low grade and stage Type I
      endometrial cancer. Subsequently, Illumina paired-end RNA sequencing was
      performed, followed by bioinformatics analysis, to determine differential
      transcriptome expression patterns. RESULTS: LINC00958 was upregulated in all
      three cancers, and four lincRNAs including LINC01480, LINC00645, LINC00891 and
      LINC00702 demonstrated exquisite specificity for malignant endometrium compared
      to normal endometrium while also distinguishing endometrial cancer from ovarian
      and cervical cancers. Furthermore, LINC01480 has features required to express a
      micropeptide. CONCLUSIONS: The lincRNAs, characterised in this study, represent
      high priority genes to be tested for functional significance in the pathogenesis
      and/or progression of endometrial cancer. Furthermore, lincRNAs have potential to
      be released into the bloodstream and therefore the four lincRNAs identified here
      may represent biomarkers for early detection of endometrial cancer without
      biopsy.

PMID- 29050780
TI  - Preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives and their
      activity against DOT1L.
AB  - From a readily available 5-C-Me ribofuranoside, we have realized a reliable route
      to valuable 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives at gram scale
      with confirmed stereochemistry. These adenosine derivatives are useful starting
      materials for the preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine
      derivatives with higher complexity. From one of the new adenosine derivatives,
      some 5'-deoxy-5'-amino-5'-C-methyl adenosine DOT1L inhibitors were prepared in
      several steps. Data from DOT1L assay indicated that additional 5'-C-Me group
      improved the enzyme inhibitory activity.

PMID- 29050781
TI  - Examination of alpha-exosite inhibitors against Botulinum neurotoxin A protease
      through structure-activity relationship studies of chicoric acid.
AB  - Botulinum neurotoxins (BoNT) are among the most toxic known substances and
      currently there are no effective treatments for intraneuronal BoNT intoxication.
      Chicoric acid (ChA) was previously reported as a BoNT/A inhibitor that binds to
      the enzyme's alpha-exosite. Herein, we report the synthesis and structure
      activity relationships (SARs) of a series of ChA derivatives, which revealed
      essential binding interactions between ChA and BoNT/A. Moreover, several ChA
      based inhibitors with improved potency against the BoNT/A were discovered.

PMID- 29050782
TI  - Development of a peptide-based inducer of protein degradation targeting NOTCH1.
AB  - We previously developed a protein knockdown system by small-molecule hybrid
      compounds named SNIPERs (Specific and Nongenetic IAP-dependent Protein Erasers).
      Here we report a peptide-based protein knockdown system for inducing degradation
      of a transcriptional factor NOTCH1. The molecules designed were composed of two
      biologically active scaffolds: a peptide that binds to the surface of the target
      protein NOTCH1 and a small-molecule MV1 that binds to the E3 ubiquitin ligase
      inhibitor of apoptosis protein (IAP), which are expected to cross-link these
      proteins in cells. Hybrid molecules specifically induced the degradation of the
      NOTCH1 protein by the proteasome. This system could be a useful method to develop
      various degradation inducers against a large number of proteins to which small
      molecule ligands have not been found.

PMID- 29050783
TI  - Design and synthesis of a novel series of (1'S,2R,4'S)-3H-4'
      azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2'-bicyclo[2.2.2]octanes] with high
      affinity for the alpha7 neuronal nicotinic receptor.
AB  - We describe an efficient and convergent synthesis of a series of (1'S,2R,4'S)-3H
      4'-azaspiro[benzo[4,5]imidazo[2,1-b]oxazole-2,2'-bicyclo[2.2.2]octanes]
      displaying potency for the alpha7 nicotinic acetylcholine receptor (nAChR) and
      good selectivity vs. the related 5-HT3A receptor.

PMID- 29050784
TI  - Novel potentially antifungal hybrids of 5-flucytosine and fluconazole: Design,
      synthesis and bioactive evaluation.
AB  - A series of novel potentially antifungal hybrids of 5-flucytosine and fluconazole
      were designed, synthesized and characterized by 1H NMR, 13C NMR, IR and HRMS
      spectra. Bioactive assay manifested that some prepared compounds showed moderate
      to good antifungal activities in comparison with fluconazole and 5-flucytosine.
      Remarkably, the 3,4-dichlorobenzyl hybrid 7h could inhibit the growth of C.
      albicans ATCC 90023 and clinical resistant strain C. albicans with MIC values of
      0.008 and 0.02 mM, respectively. The active molecule 7h could not only rapidly
      kill C. albicans but also efficiently permeate membrane of C. albicans. Molecular
      docking study revealed that compound 7h could interact with the active site of
      CACYP51 through hydrogen bond. Quantum chemical studies were also performed to
      explain the high antifungal activity. Further preliminary mechanism research
      suggested that molecule 7h could intercalate into calf thymus DNA to form a
      steady supramolecular complex, which might block DNA replication to exert the
      powerful bioactivities.

PMID- 29050785
TI  - Spinal dural arteriovenous fistulas: Early endovascular treatment or surgery?

PMID- 29050786
TI  - Homocysteine in non-valvular atrial fibrillation: Role and clinical implications.
AB  - Atrial fibrillation (AF), the most common sustained arrhythmia, is associated
      with a series of adverse complications that cause so-called AF socioeconomic
      burden. Apart from the classical risk factors, it seems to be novel factors that
      increase the risk of AF and AF-related stroke. Recently, more and more evidence
      has well documented the close relationships between homocysteine (Hcy) and AF. As
      a well-known marker for pro-oxidation and pro-inflammation, Hcy plays an
      important role in a number of vascular diseases having strong association with
      AF. This review will discuss the expression of Hcy and its association with
      ischemic stroke in AF patients especially for elderly patients, and the role and
      clinical implications of Hcy in the thromboembolic events and rhythm outcome in
      AF patients. The possible mechanisms linking elevated Hcy and cardiovascular
      events in AF patients will also be addressed, including oxidative stress,
      inflammatory response, atrial remodeling, etc.

PMID- 29050788
TI  - Drooling in Parkinson's disease patients.

PMID- 29050787
TI  - Transplantation routes affect the efficacy of human umbilical cord mesenchymal
      stem cells in a rat GDM model.
AB  - Gestational diabetes mellitus (GDM) is harmful to both the mother and fetus.
      Although transplantation of human umbilical cord mesenchymal stem cells (HUMSCs)
      could be a useful therapy for GDM, the influences of different transplantation
      routes on the therapeutic effects remain unclear. In this study, we isolated and
      cultured the HUMSCs for transplantation, and the biological activity of HUMSCs
      was verified by flow cytometric analysis (the positive markers, CD44, CD73, CD105
      and CD90, the negative markers, CD45, CD34, CD19, HLA-DR, and CD11b) and potency
      of osteogenic, adipogenic and chondrogenic differentiation. Streptozotocin (STZ)
      induced diabetes mellitus (DM)/GDM rats were transplanted with HUMSCs by
      different routes: single or multiple tail vein injection, liver parenchyma, and
      renal capsule transplantation. These were compared to positive controls (STZ
      induced, untreated) and negative controls (non-induced, untreated) to determine
      the effect of the transplant on the control of DM/GDM. The blood glucose level
      and body weight of rats in each group were determined and showed different
      effects. Transplantation of HUMSCs to GDM rats can increase the number of
      offspring in comparison to the negative controls. The weight of the offspring in
      the transplantation groups also increased due to the therapeutic effect of
      HUMSCs. Based on results, we concluded that transplanting HUMSCs could
      effectively alleviate the symptoms of elevated blood glucose and weight loss and
      improve the body weight and survival rate of offspring. Injections of HUMSCs were
      required to persistently decrease the blood glucose of DM and GDM rats.
      Transplanting HUMSCs into the liver or renal capsule of GDM rats led to a similar
      efficiency of controlling blood glucose and compensation for body weight. HUMSCs
      therapy increased the number and body weight of offspring and improved their
      activity. In summary, this study has enabled progress toward determining the
      optimal route for GDM therapy.

PMID- 29050789
TI  - Satisfaction With Life Over Time in People With Burn Injury: A National Institute
      on Disability, Independent Living, and Rehabilitation Research Burn Model System
      Study.
AB  - OBJECTIVE: To examine trajectories of satisfaction with life (SWL) of burn
      survivors over time and their clinical, demographic, and other predictors.
      DESIGN: Longitudinal survey. SETTING: Not applicable. PARTICIPANTS: Individuals
      >=18 years of age who underwent burn-related surgery and met one of the following
      criteria: (1) >10% total body surface area (TBSA) burn and >=65 years of age; (2)
      >20% TBSA burn and 18 to 64 years of age; (3) electrical high voltage/lightning
      injury; or (4) burn injury to the hands, face, or feet. The participants (N=378)
      had data on all variables of interest and were included in the analyses.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Satisfaction With Life
      Scale. RESULTS: Growth mixture modeling identified 2 classes with different
      trajectories of SWL. The mean SWL of the unchanged class (n=224, 60%) was flat
      over 2 years with high initial SWL scores. The SWL of the dissatisfied class
      (n=154, 40%) was at the low end of average and got progressively worse over time.
      CONCLUSIONS: SWL after burn injury can be described by 2 different trajectories
      with substantially different outcomes. Older age, worse mental health, and
      unemployment prior to injury predicted membership in the dissatisfied class.
      Additional services could be provided to those at high risk for low SWL to
      achieve better outcomes.

PMID- 29050790
TI  - Effects of a nicotinic agonist on the Brief Psychiatric Rating Scale five-factor
      subscale model in schizophrenia.

PMID- 29050791
TI  - Importance of considering the role of tetraethyl lead when examining the
      relationship between environmental pollution and psychotic disorders.

PMID- 29050792
TI  - Comparison of molecular detection PCR methods for chequa iflavirus in freshwater
      crayfish, Cherax quadricarinatus.
AB  - Chequa iflavirus (+ve sense ssRNA virus) infects redclaw crayfish (Cherax
      quadricarinatus) and it may cause mortality reaching 20-40% after about three
      weeks following stress. The sequence of the RNA-dependent RNA polymerase at
      nucleotide position 8383-9873 was used for developing and comparing PCR-based
      detection protocols. The reverse transcription, quantitative, polymerase chain
      reaction (RT-qPCR) was specific against nine Picornavirales and crustacean
      viruses and its' measurement of uncertainty (0.07-1.37) was similar to PCRs for
      other crustacean viruses. In vitro, the reverse transcription loop-mediated
      isothermal amplification (RT-LAMP) read at 60min had poor repeatability for a
      linearized plasmid with an iflavirus insert when compared with RT-PCR visualised
      on an electrophoretic gel and RT-qPCR; both sensitive to 102 copies. In a
      limited, comparative sample of clinical crayfish haemolymph, the lowest, non-zero
      copies were 2.88*104 for RT-PCR and 4.60*101 for the RT-qPCR. In 68 further
      clinical crayfish haemolymph samples tested by RT-qPCR only, copy numbers ranged
      from 0 to 1.14*106. For RT-qPCR, the amplification plots, melt curves and the CT
      values indicated that the CT above 34.0 is a potential negative result but
      examination of the melt curve is necessary for an accurate interpretation. A
      suggested program of testing for crayfish farmers would consist of non
      destructive bleeding, labelling of crayfish and screening with RT-qPCR. Only
      those crayfish nominally negative (below detectable limits) would be used for
      broodstock or selective breeding.

PMID- 29050793
TI  - Anaplasmosis in pediatric patients: Case report and review.
AB  - Human granulocytic anaplasmosis (HGA) is a tick-borne infection, characterized as
      an acute and sometimes severe febrile illness which may be associated with
      leukopenia and thrombocytopenia. Most case reports of HGA have been in adults,
      with only 8 case reports of HGA in children. We add a ninth case of HGA, which
      occurred in a 5-year-old. The paucity of pediatric HGA case reports maybe because
      publication bias, or HGA in children is a mild illness and children with HGA are
      less likely than adults to seek medical care, or the diagnosis of HGA requires a
      blood draw and adults (versus children) are more likely to get diagnostic
      testing. The 9 case reports in children suggest that pediatric HGA is usually a
      mild infection and that doxycycline and rifampin are effective therapies. Like
      adults, children with HGA frequently present with fever, headache, and malaise;
      however, children are more likely than adults to have abdominal pain as a
      prominent complaint.

PMID- 29050794
TI  - Genomic Quantitative Genetics to Study Evolution in the Wild.
AB  - Quantitative genetic theory provides a means of estimating the evolutionary
      potential of natural populations. However, this approach was previously only
      feasible in systems where the genetic relatedness between individuals could be
      inferred from pedigrees or experimental crosses. The genomic revolution opened up
      the possibility of obtaining the realized proportion of genome shared among
      individuals in natural populations of virtually any species, which could promise
      (more) accurate estimates of quantitative genetic parameters in virtually any
      species. Such a 'genomic' quantitative genetics approach relies on fewer
      assumptions, offers a greater methodological flexibility, and is thus expected to
      greatly enhance our understanding of evolution in natural populations, for
      example, in the context of adaptation to environmental change, eco-evolutionary
      dynamics, and biodiversity conservation.

PMID- 29050795
TI  - Evolutionary Trade-Off between Secondary Sexual Traits and Ejaculates.
AB  - Recent theoretical models predict that the evolutionary diversification of the
      weapons and ornaments of pre-mating sexual selection should be influenced by
      trade-offs with male expenditure on ejaculates. However, the patterns of
      association between secondary sexual traits and ejaculate expenditure are
      frequently inconsistent in their support of this prediction. We show why
      consideration of additional life-history, ecological, and mating-system variables
      is crucial for the interpretation of associations between secondary sexual traits
      and ejaculate production. Incorporation of these 'missing variables' provides
      evidence that interactions between pre- and post-mating sexual selection can
      underlie broad patterns of diversification in male weapons and ornaments. We call
      for more experimental and genetic approaches to uncover trade-offs, as well as
      for studies that consider the costs of mate-searching.

PMID- 29050796
TI  - Sites of infection associated with Streptococcus anginosus group among children.
AB  - Streptococcus anginosus group (SAG) are parts of normal flora of the oral cavity
      and associated with abscess forming in various sites on the body. Although the
      clinical features of infections caused by each member of the SAG in adults has
      been reported, it has not well been known in children. The aim of this study was
      to clarify the site of infections associated with individual SAG species among
      children. Medical records from March 2010 to July 2016 were reviewed at Tokyo
      Metropolitan Children's Medical Center. Any SAG species (S. anginosus, S.
      constellatus, or S. intermedius) isolated from clinical samples and recorded in
      the microbiological database were included for analysis. Analysis of 52
      infectious episodes found that S. anginosus was most frequently isolated from the
      genitourinary tract, and 73% of genitourinary tract infection was
      balanoposthitis. All genitourinary tract infections were associated with S.
      anginosus. These findings were different from those of a previous study of
      adults. Of all the patients, 45 patients (87%) had polymicrobial infections. More
      than 70% of patients infected by S. anginosus and S. constellatus were co
      infected by obligate anaerobes, in comparison with only 21% of S. intermedius
      cases. Among the obligate anaerobes species, Bacteroides spp. was significantly
      accompanied with S. anginosus. Susceptibility to penicillin, ampicillin,
      cefotaxime, erythromycin, clindamycin, levofloxacin, and vancomycin was 100%,
      100%, 100%, 77%, 89%, 97% and 100%, respectively. S. anginosus was often isolated
      from balanoposthitis among children.

PMID- 29050798
TI  - Animals, anxiety, and anxiety disorders: How to measure anxiety in rodents and
      why.
AB  - Measurement of anxiety is desirable for the benefit of drug development and
      understanding the brain function and mental well-being. Animal models offer the
      advantages of detailed neurobiological analysis, experimental manipulation of
      specific components in the brain circuits that underlie psychopathology, and the
      possibility of screening novel drugs with clinical potential. A large variety of
      animal models of anxiety and screening tests of anxiolytics is currently in use.
      While their value in advancing the knowledge and predicting therapeutic success
      of drugs is unquestionable, the expectations have grown much higher, and the
      frustration over absence of novel successful drug concepts is rising. It is
      argued that the multitude of factors that can interfere with animal behaviour in
      anxiety tests, and the complexity of neurobiology of the various anxiety
      disorders, present high demands on validation of each anxiety test within each
      specific laboratory condition. Anxiety models should be explicitly related to a
      theoretical paradigm on underlying neurobiology, because there is a diversity in
      concepts, and validation of the model and the selection of behavioural readouts
      is critically dependent on the neurobiological model. Environmental conditions
      during the model production and anxiety testing need more attention, including
      the less considered factors such as ultrasounds. More attention is required to
      the differences in anxiety neurobiology between males and females, and inter
      individual differences in coping strategies.

PMID- 29050799
TI  - Introduction.

PMID- 29050797
TI  - 25-Year Physical Activity Trajectories and Development of Subclinical Coronary
      Artery Disease as Measured by Coronary Artery Calcium: The Coronary Artery Risk
      Development in Young Adults (CARDIA) Study.
AB  - OBJECTIVE: To evaluate 25-year physical activity (PA) trajectories from young to
      middle age and assess associations with the prevalence of coronary artery
      calcification (CAC). PATIENTS AND METHODS: This study includes 3175 participants
      in the Coronary Artery Risk Development in Young Adults (CARDIA) study who self
      reported PA by questionnaire at 8 follow-up examinations over 25 years (from
      March 1985-June 1986 through June 2010-May 2011). The presence of CAC (CAC>0) at
      year 25 was measured using computed tomography. Group-based trajectory modeling
      was used to identify PA trajectories with increasing age. RESULTS: We identified
      3 distinct PA trajectories: trajectory 1, below PA guidelines (n=1813; 57.1%);
      trajectory 2, meeting PA guidelines (n=1094; 34.5%); and trajectory 3, 3 times PA
      guidelines (n=268; 8.4%). Trajectory 3 participants had higher adjusted odds of
      CAC>0 (adjusted odds ratio [OR], 1.27; 95% CI, 0.95-1.70) vs those in trajectory
      1. Stratification by race showed that white participants who engaged in PA 3
      times the guidelines had higher odds of developing CAC>0 (OR, 1.80; 95% CI, 1.21
      2.67). Further stratification by sex showed higher odds for white males (OR,
      1.86; 95% CI, 1.16-2.98), and similar but nonsignificant trends were noted for
      white females (OR, 1.71; 95% CI, 0.79-3.71). However, no such higher odds of
      CAC>0 for trajectory 3 were observed for black participants. CONCLUSION: White
      individuals who participated in 3 times the recommended PA guidelines over 25
      years had higher odds of developing coronary subclinical atherosclerosis by
      middle age. These findings warrant further exploration, especially by race, into
      possible biological mechanisms for CAC risk at very high levels of PA.

PMID- 29050800
TI  - A ruptured pulmonary arteriovenous fistula after laparoscopic operation.
AB  - Pulmonary arteriovenous fistula (PAVF) is a rare anomaly in the lung, and
      hemothorax or massive hemoptysis due to spontaneous rupture of the fistula sac is
      even rarer. The patient described here was a 47-year-old woman who presented with
      massive hemoptysis resulting from the rupture of her PAVF just after laparoscopic
      operation. To our knowledge, this may be the first case ever reported that the
      rupture of PAVF may be correlated with a laparoscopic operation. The patient
      survived without adverse events after emergency pulmonary lobectomy.

PMID- 29050801
TI  - Projections of zoster incidence in Australia based on demographic and
      transmission models of varicella-zoster virus infection.
AB  - Re-exposure to varicella infection is believed to delay the occurrence of herpes
      zoster (HZ), which has led to predictions of increased HZ following introduction
      of varicella vaccination programs. However, there is evidence of rising HZ rates
      before vaccination was introduced. Here, we explore a potential explanation for
      this effect through demographic change leading to reductions in varicella
      exposure and boosting in the context of Australia over the 20th century. To study
      this hypothesis, we integrated observed changes in Australian birth and age
      specific death rates with a varicella transmission model. The model was then
      calibrated to age-specific pre-vaccination seroprevalence (1997-9) and
      hospitalization data (1993-2009). Model simulations predicted that declining
      birth rates led to a 50% reduction in varicella incidence over the 20th century.
      When combined with the impacts of an aging population, the simulations further
      suggested that HZ incidence should have increased by 50% over the 20th century.
      However, we found that after age-standardization, the residual increase in HZ due
      to reduced boosting was only about 8% over the 20th century. Results were also
      sensitive to the assumed duration of immunity to HZ and whether multiple HZ
      episodes were possible. Despite a strong predicted effect of demographic change
      on varicella incidence, our findings suggest that improved survival is the main
      contributor to any rise in HZ rates prior to vaccination in Australia. Removing
      survival effects through age-standardization is recommended when considering
      epidemiologic or model-based analysis of past trends in HZ.

PMID- 29050802
TI  - Episode of Kasabach-Merritt phenomenon following Japanese encephalitis
      vaccination: Case report.
AB  - Kasabach-Merritt phenomenon (KMP) is a rare potentially life-threatening
      consumptive coagulopathy characterized by thrombocytopenia and hypofibrinogenemia
      occurring associated with the vascular tumors kaposiform hemangioendothelioma
      (KHE) and tufted angioma (TA). A 10-month old male infant, diagnosed with KHE on
      his left leg, underwent a rapid increase of the lesion and severe
      thrombocytopenia, one day after the first dose of inactivated Japanese
      encephalitis (JE) vaccination. The episode of KMP was treated successfully by
      steroid. KMP is a rare complication of vaccination that physicians should be
      aware of. Giving up the following vaccination to provide the recurrence of KMP is
      not recommended.

PMID- 29050803
TI  - Selection of a platinum-binding sequence in a loop of a four-helix bundle
      protein.
AB  - Protein-metal hybrids are functional materials with various industrial
      applications. For example, a redox enzyme immobilized on a platinum electrode is
      a key component of some biofuel cells and biosensors. To create these hybrid
      materials, protein molecules are bound to metal surfaces. Here, we report the
      selection of a novel platinum-binding sequence in a loop of a four-helix bundle
      protein, the Lac repressor four-helix protein (LARFH), an artificial protein in
      which four identical alpha-helices are connected via three identical loops. We
      created a genetic library in which the Ser-Gly-Gln-Gly-Gly-Ser sequence within
      the first inter-helical loop of LARFH was semi-randomly mutated. The library was
      then subjected to selection for platinum-binding affinity by using the T7 phage
      display method. The majority of the selected variants contained the Tyr-Lys-Arg
      Gly-Tyr-Lys (YKRGYK) sequence in their randomized segment. We characterized the
      platinum-binding properties of mutant LARFH by using quartz crystal microbalance
      analysis. Mutant LARFH seemed to interact with platinum through its loop
      containing the YKRGYK sequence, as judged by the estimated exclusive area
      occupied by a single molecule. Furthermore, a 10-residue peptide containing the
      YKRGYK sequence bound to platinum with reasonably high affinity and basic side
      chains in the peptide were crucial in mediating this interaction. In conclusion,
      we have identified an amino acid sequence, YKRGYK, in the loop of a helix-loop
      helix motif that shows high platinum-binding affinity. This sequence could be
      grafted into loops of other polypeptides as an approach to immobilize proteins on
      platinum electrodes for use as biosensors among other applications.

PMID- 29050804
TI  - Polyhydroxyalkanoate accumulation ability and associated microbial community in
      activated sludge-derived acetate-fed microbial cultures enriched under different
      temperature and pH conditions.
AB  - The influence of temperature and pH during enrichment on the polyhydroxyalkanoate
      (PHA) accumulation ability and composition of PHA-accumulating microorganisms
      (PHAAMOs) in enrichment cultures was investigated. Enrichment of PHAAMOs from
      activated sludge was conducted in acetate-fed sequencing batch reactors using a
      feast-famine regime under different temperature (20 degrees C, 28 degrees C, and
      36 degrees C) and pH (controlled at 7.2 or not) conditions. PHA accumulation
      ability, which was evaluated in nitrogen- and phosphorus-deficient 24-h single
      batch cultures, was greatly enhanced by enrichment, irrespective of the
      temperature and pH. Enrichment at 20 degrees C or 28 degrees C and without pH
      control seemed most appropriate for strong PHA accumulation. Analyses of the
      PHAAMO composition by the clone library method targeting phaC genes, which encode
      the class I and II PHA synthases, revealed that Burkholderiales were the dominant
      PHAAMOs in the seed sludge, while Rhodocyclales, specifically Azoarcus spp. and
      Thauera spp., were dominant after enrichment without pH control, showing a strong
      ability to accumulate PHA. The results indicated that Azoarcus spp. and Thauera
      spp. are key PHAAMOs in an enrichment culture based on the feast-famine method,
      with high PHA accumulation ability.

PMID- 29050805
TI  - Modelling of thrombin generation under flow in realistic left anterior descending
      geometries.
AB  - Currently there are no available methods for prediction of thrombotic
      complications in Coronary Artery disease. Additionally, blood coagulation tests
      are mainly performed in a steady system while coagulation in vivo occurs under
      flow conditions. In this work, a phenomenological model for coagulation up-to
      thrombin generation is proposed; the model is mainly based on the results of
      thrombin generation assays and therefore it can account for the variation of the
      coagulability that is observed in different individuals. The model is applied on
      3 cases of left anterior descending arteries (LAD) with 50% maximum stenosis
      placed at a different location and have been statistically assessed as of
      different complication risk. The simulations showed that parameters of thrombin
      generation assays obtain different values when they refer to thrombin generation
      under realistic coronary flow conditions. The flow conditions prevailing locally
      because of the geometric differences among the arterial trees can lead to
      different initiation times and thrombin production rates and it also alters the
      spatial distribution of the coagulation products. Similarly, small changes of the
      coagulation characteristics of blood under identical flow conditions can allow or
      prevent the initiation of coagulation. The results indicate that combined
      consideration of geometry and coagulation characteristics of blood can lead to
      entirely different conclusions compared to independent assessment of each factor.

PMID- 29050806
TI  - Immune checkpoint inhibitor-associated CNS autoimmune disorder (ICICAD) following
      nivolumab treatment: A new entity of drug-induced autoimmune encephalitis?

PMID- 29050807
TI  - The relationship between gluten free diet adherence and depressive symptoms in
      adults with coeliac disease: A systematic review with meta-analysis.
AB  - PURPOSE: Depressive symptoms are common in patients with coeliac disease (CD) and
      may represent a barrier to gluten free diet (GFD) adherence. The aims of this
      meta-analysis were: (1) to synthesise the evidence on the relationship between
      depression or depressive symptoms and degree of adherence to a GFD in patients
      with CD who are already attempting a GFD (i.e., post-diagnosis and onset of GFD),
      and (2) to summarise the direction of causation of any observed relationship.
      METHODS: A random effects meta-analysis of 8 cross-sectional studies (N = 1644)
      was conducted. Included studies measured self-reported depressive symptoms and
      GFD adherence using either a dietitian interview or validated self-report
      questionnaire that considered unintentional gluten consumption. RESULTS: There
      was a moderate association between poorer GFD adherence and greater depressive
      symptoms (r = 0.398, 95% CI = 0.321-0.469), with marked heterogeneity in the
      effects (I2 = 66.8%). A sensitivity analysis excluding studies with a
      moderate/high (k = 1) or unclear risk of bias (k = 1) did not change the results.
      CONCLUSION: The low number of studies meeting inclusion criteria limits the
      strength of the conclusions. Available evidence suggests there is an association
      between poorer GFD adherence and self-reported depressive symptoms; however,
      studies using longitudinal and prospective designs, and reliable measures,
      particularly for adherence, are needed to confirm this association. The direction
      of causation between depression and adherence remains unclear.

PMID- 29050808
TI  - An indirect pro-environmental behavior: Public support for waste management
      policy.

PMID- 29050809
TI  - Burnout, hair cortisol, and timing: Hyper- or hypocortisolism?

PMID- 29050810
TI  - How to not detonate the bomb: the case of the Italian National Health Service.
AB  - Why is Italy one of the world's highest ranked for ability and quality of
      healthcare in relationship to the resources invested? The last decade has been
      characterized by many Italian Regions with Recovery Plans, whose main focus was
      on short-term issues with a high impact on healthcare costs. Italy is now leaving
      this phase and at the regional level there will be an increase of new hirings in
      the healthcare sectors, as stated by the Ministry of Health. There is a large
      amount of scientific literature that supports the role of factors such as
      lifestyles, diet and genetics as the base of population health. The success of
      the Italian National Health Service (INHS) function is rooted in the ability of a
      system to adapt to evolving situations, but it is also important to ensure a
      mechanism of positive feedback correction. In the future, INHS will require a new
      set of reforms, like the redefinition of structures and mechanisms of governance,
      the implementation of strategic plans that conjugate better clinical and
      financial issues. In this context, Health Data Entanglement could be an option to
      improve the effectiveness of the health governance system in order to develop
      better quality of care. In Public Health several criticisms could detonate the
      bomb, and above all the decreasing levels of primary prevention in the fight to
      obesity (promoting the Mediterranean Diet and physical activity), to smoking and
      alcohol consumption, as well as to infectious diseases (promoting high
      vaccination rates). Secondary prevention is also key to this function as a
      practical experience of re-engineering of the public expense, giving much
      attention to what works in terms of cost effectiveness, and in particular to
      cancer screening.

PMID- 29050811
TI  - Italian National Health Service: defusing the bomb.

PMID- 29050812
TI  - Response to editor regarding "Improvement of psychiatric symptoms in youth
      following resolution of sinusitis".

PMID- 29050813
TI  - Changes in prevalence of hepatitis A and associated factors in Setif-Algeria.
AB  - Hepatitis A, a waterborne disease associated with fecal contamination, remains
      the most common acute hepatitis worldwide. Generally considered to be a disease
      affecting children living in poor sanitary conditions, hepatitis A affects the
      adult population if hygiene improves. Studies conducted during the 1980s ranked
      Algeria as a highly endemic area. Thirty years on, we conducted this cross
      sectional epidemiological study with the main objective of estimating the
      seroprevalence of hepatitis A virus infection in the district of Setif, Algeria.
      A survey was carried out between June 2010 and September 2011 and focused on 1061
      individuals aged 5-19 years old. The seroprevalence of hepatitis A was estimated
      at 72.3% and varied with age: 56.9% in children aged 5-9 years, 70.4% among those
      aged 10-14 years, and 85.4% for the 15-19-year-old age group. Factors associated
      with lower seroprevalence were mainly related to a higher socioeconomic level,
      including living in an urban area, small household size, parents with a higher
      educational level, and consumption of bottled mineral water. This study
      highlights an epidemiological change and predicts that Algeria is in a period of
      gradual transition to intermediary endemicity. This change is synonymous with a
      susceptible population growing older, suggesting that serious forms of hepatitis
      can be expected more frequently. The current preventive strategy against
      hepatitis A should be revisited.

PMID- 29050814
TI  - Ultrasound-derived three-dimensional print models made ultrasimply.

PMID- 29050815
TI  - Right ventricular outflow tract reintervention after primary tetralogy of Fallot
      repair in neonates and young infants.
AB  - OBJECTIVE: To assess the outcomes following primary tetralogy of Fallot (TOF)
      repair in neonates and young infants with pulmonary stenosis (PS) and pulmonary
      atresia and compare differences in reintervention on the right ventricular
      outflow tract (RVOT) among those undergoing valve sparing repair (VSR),
      transannular RVOT patch (TAP), and right ventricle-to-pulmonary artery (RV-PA)
      conduit surgeries. METHODS: Data were collected retrospectively in 101 patients
      who underwent TOF repair over a 10-year period between January 2005 and September
      2015. The primary endpoint was reintervention on the RVOT, defined as a surgical
      procedure or cardiac catheterization-based RVOT reintervention. RESULTS: Forty
      three patients had TOF/PS, of whom 24 (56%) underwent TAP and 19 (44%) underwent
      VSR. Fifty-eight patients had TOF/PA, 14 (24%) underwent TAP and 44 (76%)
      underwent RV-PA conduit repair. Overall patient mortality was 2.9% (3 of 101).
      Thirty-three patients underwent surgical reintervention, and 52 underwent
      catheterization-based reintervention. Patients with TOF/PA who underwent RV-PA
      conduit repair had a higher surgical reintervention rate than those who underwent
      TAP (45% vs 21%). Patients with TOF/PSs undergoing VSR with a lower median birth
      weight (2.5 kg vs 3.7 kg) required more surgical reintervention. CONCLUSIONS:
      Neonatal TOF repair can be performed with low mortality but frequent RVOT
      reinterventions. Surgical reintervention is earlier and the rate is higher among
      patients with TOF/PA undergoing RV-PA conduit repair compared with those
      undergoing TAP. Although there were no overall differences in RVOT reintervention
      rate between patients with TOF/PS undergoing VSR and those undergoing TAP, a
      lower birth weight in the patients undergoing VSR is associated with a higher
      surgical reintervention rate.

PMID- 29050816
TI  - Applicability of handmade expanded polytetrafluoroethylene trileaflet-valved
      conduits for pulmonary valve reconstruction: An ex vivo and in vivo study.
AB  - OBJECTIVE: The handmade expanded polytetrafluoroethylene (ePTFE) trileaflet
      valved conduit could potentially be used as a substitute pulmonary valve
      replacement material, especially in children. The current study investigated (1)
      the function of the ePTFE trileaflet-valved conduits in an ex vivo experimental
      system and (2) the short-term performance of the conduit in a porcine model to
      verify its clinical applicability. METHODS: The competency of the ePTFE
      trileaflet-valved conduits was estimated through ex vivo (using a pulmonary mock
      circulation loop) and in vivo (in a porcine model with a damaged pulmonary valve)
      experiments. Explants were examined by gross morphology and histopathologic
      examination. RESULTS: In the ex vivo experiment, the ePTFE trileaflet-valved
      conduits were determined to effectively increase mean pulmonary pressure from
      10.2 to 14.4 mm Hg compared with defective silicon-valved conduits. In addition,
      the regurgitation fraction value of ePTFE trileaflet-valved conduits was 15.9% to
      18.1%, which was significantly better than the defective valve conduits
      (regurgitation fraction = 73.5%-85.7%). In the in vivo experiment, the valved
      conduits were confirmed to be with good valve position maintenance, and the valve
      and leaflets showed no signs of thickening or peeling after a short-term
      implantation period. There were also no significant signs of inflammation
      reaction on histopathologic examination. CONCLUSIONS: The ePTFE trileaflet-valved
      conduits for pulmonary valve reconstruction showed acceptable performance and
      outcomes in the ex vivo and in vivo experiments. The ePTFE trileaflet-valved
      conduit may be clinically useful, although additional studies in animals should
      be conducted to determine its long-term outcomes.

PMID- 29050817
TI  - Zirconia surface modification by a novel zirconia bonding system and its adhesion
      mechanism.
AB  - OBJECTIVE: Bonding to zirconia has been of great interest over the last 10-15
      years. The aim of this study was to develop a zirconia bonding system and clarify
      its adhesion mechanism. METHODS: A zirconia primer was prepared using tetra-n
      propoxy zirconium (TPZr) and water. A silane primer was also prepared using gamma
      methacryloyloxypropyltrimethoxysilane (gamma-MPS) and hydrochloric acid. After
      the zirconia primer was applied to the oxidized zirconia surface, the silane
      primer was applied to the ZrO2-functionalized layer and the resin cement was
      applied to the silane-modified layer. Ceramic Primer II was used as a typical MDP
      based ceramic primer. Shear bond strengths were measured using a universal
      testing machine. To clarify the enhancing mechanism of the zirconia bonding
      system, X-ray photoelectron spectroscopy (XPS) analyses were performed. RESULTS:
      The zirconia bond strength was affected by the surface wettability of zirconia,
      and the compositions of TPZr and water utilized in the zirconia primer. When the
      zirconia primer, consisting of 10MUL TPZr and 13MUL water, was applied to the
      zirconia surface that had been oxidized by H2O2 above 10%, the maximum bond
      strength of 8.2MPa was obtained. The mechanism of the zirconia bonding system was
      established as follows: the hydrolyzed zirconium species formed a more reactive
      ZrO2-functionalized layer on the oxidized zirconia surface, and the hydrolyzed
      gamma-MPS species adsorbed on that layer introduces a chemical bonding to the
      resin. SIGNIFICANCE: The novel zirconia bonding system enhanced the bonding
      performance of the resin, and showed a greater bond strength than an MDP-based
      ceramic primer.

PMID- 29050818
TI  - Decreased serum levels of sCD40L and IL-31 correlate in treated patients with
      Relapsing-Remitting Multiple Sclerosis.
AB  - The CD40/CD40L system is a binding key for co-stimulation of immune cells.
      Soluble form of CD40L has been widely studied as marker of inflammatory and
      autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as
      14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer
      acetate or Interferon beta. In the healthy control group, we found in serum a
      highly positive correlation between sCD40L and Interleukin (IL)-31, an anti
      inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and
      sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression
      and complete depletion of CD40L mRNA, detected from peripheral blood cells, was
      found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into
      account as possible prognostic markers when analyzing the disease progress of MS
      in order to provide more personalized treatment.

PMID- 29050819
TI  - RelB regulates Th17 differentiation in a cell-intrinsic manner.
AB  - The role of the alternative NF-kappaB pathway is mainly attributed to the
      lymphoid organ formation and blood cancer. However, its involvement in lymphocyte
      differentiation is not clearly defined. Recently, we have shown that uncontrolled
      activation of alternative NF-kappaB in mice lacking the NF-kappaB inhibitory
      protein p100 (p100-/- mice) hinders plasmablast proliferation and diminishes T
      cell independent responses. Here we show that hyperactivation of this pathway
      leads to a cell-intrinsic T cell defects. p100-deficient T helper cells displayed
      both an activation and a proliferation defect in vitro. In addition, memory T
      cell formation was impaired in vivo. Moreover, p100-/- T cells failed to polarize
      into T helper 17 cells. This phenotype was dependent on increased RelB activation
      and suboptimal RORgammat expression. Thus, our results demonstrate that RelB acts
      as a negative regulator of T cell activation and Th17 development. Targeting this
      pathway therefore could be beneficial in Th17-mediated pathologies.

PMID- 29050820
TI  - GABAB receptor modulation-to B or not to be B a pro-cognitive medicine?
AB  - Metabotropic GABAB receptors clearly modify cognitive performance in preclinical
      animal models, yet translation to treating human disease has been elusive.
      Compared to their ionotropic GABAA receptor counterpart GABAB receptors not only
      regulate postsynaptic excitability but also regulate diverse synaptic inputs by
      presynaptically inhibiting neurotransmitter release. As such, the choice of
      agonist, antagonist, -ve or +ve modulator as well as CNS exposure level, timing
      of delivery and longevity of action strongly influence the probability of
      unlocking the procognitive potential of GABAB receptors in human disease.
      Quantitative clinical analysis of target/mechanistic engagement of GABAB
      receptors within cognitive circuits at the level of distinct pre-synaptic and
      post-synaptic subpopulations is required to determine the optimal
      pharmacological/dosing profile for different cognitive disorders.

PMID- 29050821
TI  - Chiral behavior in rat tail tendon fascicles.
AB  - Ex vivo tendon mechanical behavior has been well described under rotationally
      constrained uniaxial tensile testing. During standard loading of rat tail tendon
      (RTT) fascicles, apparent axial twist has been observed. To quantify this
      behavior, we designed a custom testing setup, utilizing magnetic suspension, to
      allow unconstrained axial rotation during tensile loading. We characterized the
      rotational behavior of single and paired RTT fascicles under cyclic loading. We
      also measured stress relaxation across loading cycles as well as "rotational
      relaxation". Single fascicle nonlinear stretch-twist coupling is well described
      by the asymptotic function Deltatheta=A(1-e-Bepsilon) in which fascicles rotated
      a mean +/-51.1 degrees  within about 1% applied axial strain. On average, paired
      fascicles rotated just over 10 degrees  less. Specimen cross-sectional diameter
      had a noticeable effect on the measured mechanical properties, particularly
      effective elastic modulus. Such stretch-twist coupling and size dependence cannot
      be understood via classical elasticity but is predicted by Cosserat (micropolar)
      elasticity. The current study demonstrates RTT fascicles are chiral based on
      observed axial load-induced twist. Additionally, our findings support existing
      research that suggests a helical fascicle structure. Potential consequences of
      helical substructures, mechanical and biological, merit further investigation.

PMID- 29050822
TI  - A comparison and update of direct kinematic-kinetic models of leg stiffness in
      human running.
AB  - Direct kinematic-kinetic modelling currently represents the "Gold-standard" in
      leg stiffness quantification during three-dimensional (3D) motion capture
      experiments. However, the medial-lateral components of ground reaction force and
      leg length have been neglected in current leg stiffness formulations. It is
      unknown if accounting for all 3D would alter healthy biologic estimates of leg
      stiffness, compared to present direct modelling methods. This study compared
      running leg stiffness derived from a new method (multiplanar method) which
      includes all three Cartesian axes, against current methods which either only
      include the vertical axis (line method) or only the plane of progression
      (uniplanar method). Twenty healthy female runners performed shod overground
      running at 5.0 m/s. Three-dimensional motion capture and synchronised in-ground
      force plates were used to track the change in length of the leg vector (hip joint
      centre to centre of pressure) and resultant projected ground reaction force. Leg
      stiffness was expressed as dimensionless units, as a percentage of an
      individual's bodyweight divided by standing leg length (BW/LL). Leg stiffness
      using the line method was larger than the uniplanar method by 15.6%BW/LL (P <
      .001), and multiplanar method by 24.2%BW/LL (P < .001). Leg stiffness from the
      uniplanar method was larger than the multiplanar method by 8.5%BW/LL (6.5 kN/m)
      (P < .001). The inclusion of medial-lateral components significantly increased
      leg deformation magnitude, accounting for the reduction in leg stiffness estimate
      with the multiplanar method. Given that limb movements typically occur in 3D, the
      new multiplanar method provides the most complete accounting of all force and
      length components in leg stiffness calculation.

PMID- 29050823
TI  - Nonlinear vibrations of pre- and post-buckled lipid supramolecular micro/nano
      tubules via nonlocal strain gradient elasticity theory.
AB  - The unique geometry with high surface ratio makes lipid micro/nano-tubules as an
      excellent self-assembled supramolecular structure in various biological
      applications such as controllable release systems and drug delivery. In the
      present study, the size-dependent nonlinear vibrations of axially loaded lipid
      micro/nano tubules associated with the both prebuckling and postbuckling domains
      are explored comprehensively. To accomplish this purpose, the nonlocal strain
      gradient theory of elasticity including simultaneously two entirely different
      features of size dependency is utilized within the framework of the third-order
      shear deformable beam model. With the aid of Hamilton's principle, the non
      classical governing differential equations of motion are established
      incorporating the nonlinear prebuckling deformations and the large postbuckling
      deflections. At the end, the Galerkin method in conjunction with an improved
      perturbation technique is employed to initiate explicit analytical expressions
      for nonlocal strain gradient nonlinear frequency of pre- and post-buckled lipid
      micro/nano-tubules. It is seen that by taking the nonlocal size effect into
      consideration, the influence of geometrical parameters of the lipid micro/nano
      tubule on the nonlinear vibration characteristics within the both prebuckling and
      postbuckling domains decreases and the frequency-deflection curves are more close
      to each other. However, the strain gradient size dependency has an opposite
      effect and leads to increase the gap between the frequency-deflection curves of
      axially compressed lipid micro/nano-tubules with different geometrical
      parameters.

PMID- 29050824
TI  - In vivo repeatability of the pulse wave inverse problem in human carotid
      arteries.
AB  - Accurate arterial stiffness measurement would improve diagnosis and monitoring
      for many diseases. Atherosclerotic plaques and aneurysms are expected to involve
      focal changes in vessel wall properties; therefore, a method to image the
      stiffness variation would be a valuable clinical tool. The pulse wave inverse
      problem (PWIP) fits unknown parameters from a computational model of arterial
      pulse wave propagation to ultrasound-based measurements of vessel wall
      displacements by minimizing the difference between the model and measured
      displacements. The PWIP has been validated in phantoms, and this study presents
      the first in vivo demonstration. The common carotid arteries of five healthy
      volunteers were imaged five times in a single session with repositioning of the
      probe and subject between each scan. The 1D finite difference computational model
      used in the PWIP spanned from the start of the transducer to the carotid
      bifurcation, where a resistance outlet boundary condition was applied to
      approximately model the downstream reflection of the pulse wave. Unknown
      parameters that were estimated by the PWIP included a 10-segment linear piecewise
      compliance distribution and 16 discrete cosine transformation coefficients for
      each of the inlet boundary conditions. Input data was selected to include pulse
      waves resulting from the primary pulse and dicrotic notch. The recovered
      compliance maps indicate that the compliance increases close to the bifurcation,
      and the variability of the average pulse wave velocity estimated through the PWIP
      is on the order of 11%, which is similar to that of the conventional processing
      technique which tracks the wavefront arrival time (13%).

PMID- 29050827
TI  - Visual Working Memory Storage Recruits Sensory Processing Areas.

PMID- 29050825
TI  - Neuroimaging findings in infantile Pompe patients treated with enzyme replacement
      therapy.
AB  - BACKGROUND: Recombinant human acid alpha-glucosidase (rhGAA) enzyme replacement
      therapy (ERT) has prolonged survival in infantile Pompe disease (IPD), but has
      unmasked central nervous system (CNS) changes. METHODS: Brain imaging, consisting
      of computed tomography (CT) and/or magnetic resonance imaging (MRI), was
      performed on 23 patients with IPD (17 CRIM-positive, 6 CRIM-negative) aged 2
      38months. Most patients had baseline neuroimaging performed prior to the
      initiation of ERT. Follow-up neuroimaging was performed in eight. RESULTS:
      Sixteen patients (70%) had neuroimaging abnormalities consisting of ventricular
      enlargement (VE) and/or extra-axial cerebrospinal fluid accumulation (EACSF) at
      baseline, with delayed myelination in two. Follow-up neuroimaging (n=8) after 6
      153months showed marked improvement, with normalization of VE and EACSF in seven
      patients. Two of three patients imaged after age 10years demonstrated white
      matter changes, with one noted to have a basilar artery aneurysm. CONCLUSIONS:
      Mild abnormalities on brain imaging in untreated or newly treated patients with
      IPD tend to resolve with time, in conjunction with ERT. However, white matter
      changes are emerging as seen in Patients 1 and 3 which included abnormal
      periventricular white matter changes with subtle signal abnormalities in the
      basal ganglia and minimal, symmetric signal abnormalities involving the deep
      frontoparietal cerebral white matter, respectively. The role of neuroimaging as
      part of the clinical evaluation of IPD needs to be considered to assess for white
      matter changes and cerebral aneurysms.

PMID- 29050826
TI  - Live-cell time-lapse imaging and single-cell tracking of in vitro cultured neural
      stem cells - Tools for analyzing dynamics of cell cycle, migration, and lineage
      selection.
AB  - Neural stem cell (NSC) cultures have been considered technically challenging for
      time-lapse analysis due to high motility, photosensitivity, and growth at
      confluent densities. We have tested feasibility of long-term live-cell time-lapse
      analysis for NSC migration and differentiation studies. Here, we describe a
      method to study the dynamics of cell cycle, migration, and lineage selection in
      cultured multipotent mouse or human NSCs using single-cell tracking during a long
      term, 7-14 day live-cell time-lapse analysis. We used in-house made PDMS inserts
      with five microwells on a glass coverslip petri-dish to constrain NSC into the
      area of acquisition during long-term live-cell imaging. In parallel, we have
      defined image acquisition settings for single-cell tracking of cell cycle
      dynamics using Fucci-reporter mouse NSC for 7 days as well as lineage selection
      and migration using human NSC for 14 days. Overall, we show that adjustments of
      live-cell analysis settings can extend the time period of single-cell tracking in
      mouse or human NSC from 24-72 h up to 7-14 days and potentially longer. However,
      we emphasize that experimental use of repeated fluorescence imaging will require
      careful consideration of controls during acquisition and analysis.

PMID- 29050828
TI  - Quantification of Right Ventricular Size and Function from Contrast-Enhanced
      Three-Dimensional Echocardiographic Images.
AB  - BACKGROUND: Three-dimensional (3D) echocardiography directly assesses right
      ventricular (RV) volumes without geometric assumptions, despite the complex shape
      of the right ventricle, and accordingly is more accurate and reproducible than
      the two-dimensional methodology, which is able to measure only surrogate
      parameters of RV function. Volumetric analysis has been hampered by frequent
      inability to clearly visualize RV endocardium, especially the RV free wall, in 3D
      echocardiographic images. The aim of this study was to test the hypothesis that
      RV contrast enhancement during 3D echocardiographic imaging would improve the
      accuracy of RV volume and function analysis. METHODS: Thirty patients with a wide
      range of RV size and function and image quality underwent transthoracic 3D
      echocardiography with and without contrast enhancement and cardiovascular
      magnetic resonance imaging on the same day. RV end-diastolic and end-systolic
      volumes and ejection fraction were measured from contrast-enhanced and
      nonenhanced 3D echocardiographic images and compared with cardiovascular magnetic
      resonance reference values using linear regression and Bland-Altman analyses.
      Blinded repeated measurements were performed to assess measurement variability.
      RESULTS: RV contrast enhancement was feasible in all patients. RV volumes
      obtained both with and without contrast enhancement correlated highly with
      cardiovascular magnetic resonance (end-diastolic volume, r = 0.90 and r = 0.92;
      end-systolic volume, r = 0.92 and r = 0.94, respectively), but the correlation
      for ejection fraction was better with contrast (r = 0.87 vs r = 0.70). Biases
      were smaller with contrast for all three parameters (end-diastolic volume, -16 +/
      23 vs -36 +/- 25 mL; end-systolic volume, -10 +/- 16 vs -23 +/- 18 mL; ejection
      fraction, -0.7 +/- 5.5% vs -2.7 +/- 8.1% of the mean measured values), reflecting
      improved accuracy. Also, measurement reproducibility was improved by contrast
      enhancement. CONCLUSIONS: Contrast enhancement improves the visualization of RV
      endocardial borders, resulting in more accurate and reproducible 3D
      echocardiographic measurements of RV size and function. This approach may be
      particularly useful in patients with suboptimal image quality.

PMID- 29050829
TI  - Trace metals in soils of the bituminous sands mining region of Alberta: A
      critical, geochemical perspective on the study by Boutin and Carpenter (2017).

PMID- 29050830
TI  - Intelligent simulation of aquatic environment economic policy coupled ABM and SD
      models.
AB  - Rapid urbanization and population growth have resulted in serious water shortage
      and pollution of the aquatic environment, which are important reasons for the
      complex increase in environmental deterioration in the region. This study
      examines the environmental consequences and economic impacts of water resource
      shortages under variant economic policies; however, this requires complex models
      that jointly consider variant agents and sectors within a systems perspective.
      Thus, we propose a complex system model that couples multi-agent based models
      (ABM) and system dynamics (SD) models to simulate the impact of alternative
      economic policies on water use and pricing. Moreover, this model took the
      constraint of the local water resources carrying capacity into consideration.
      Results show that to achieve the 13th Five Year Plan targets in Dianchi, water
      prices for local residents and industries should rise to 3.23 and 4.99 CNY/m3,
      respectively. The corresponding sewage treatment fees for residents and
      industries should rise to 1.50 and 2.25 CNY/m3, respectively, assuming
      comprehensive adjustment of industrial structure and policy. At the same time,
      the local government should exercise fine-scale economic policy combined with
      emission fees assessed for those exceeding a standard, and collect fines imposed
      as punishment for enterprises that exceed emission standards. When fines reach
      500,000 CNY, the total number of enterprises that exceed emission standards in
      the basin can be controlled within 1%. Moreover, it is suggested that the volume
      of water diversion in Dianchi should be appropriately reduced to 3.06*108m3. The
      reduced expense of water diversion should provide funds to use for the
      construction of recycled water facilities. Then the local rise in the rate of use
      of recycled water should reach 33%, and 1.4 CNY/m3 for the price of recycled
      water could be provided to ensure the sustainable utilization of local water
      resources.

PMID- 29050831
TI  - Reptile road-kills in Southern Brazil: Composition, hot moments and hotspots.
AB  - Understanding road-kill patterns is the first step to assess the potential
      effects of road mortality on wildlife populations, as well as to define the need
      for mitigation and support its planning. Reptiles are one of the vertebrate
      groups most affected by roads through vehicle collisions, both because they are
      intentionally killed by drivers, and due to their biological needs, such as
      thermoregulation, which make them more prone to collisions. We conducted monthly
      road surveys (33months), searching for carcasses of freshwater turtles, lizards,
      and snakes on a 277-km stretch of BR-101 road in Southernmost Brazil to estimate
      road-kill composition and magnitude and to describe the main periods and
      locations of road-kills. We modeled the distribution of road-kills in space
      according to land cover classes and local traffic volume. Considering the
      detection capacity of our method and carcass persistence probability, we
      estimated that 15,377 reptiles are road-killed per year (55reptiles/km/year).
      Road-kills, especially lizards and snakes, were concentrated during summer,
      probably due to their higher activity in this period. Road-kill hotspots were
      coincident among freshwater turtles, lizards, and snakes. Road-kill distribution
      was negatively related to pine plantations, and positively related to rice
      plantations and traffic volume. A cost-benefit analysis highlighted that if
      mitigation measures were installed at road-kill hotspots, which correspond to 21%
      of the road, they could have avoided up to 45% of recorded reptile fatalities,
      assuming a 100% mitigation effectiveness. Given the congruent patterns found for
      all three taxa, the same mitigation measures could be used to minimize the
      impacts of collision on local herpetofauna.

PMID- 29050832
TI  - Microplastics in surface waters and sediments of the Three Gorges Reservoir,
      China.
AB  - We investigated microplastic pollution levels in surface waters and sediments
      from the Three Gorges Reservoir (TGR). The TGR is the largest reservoir in China
      and is located across the Chongqing municipality and Hubei Province. Microplastic
      abundance in the surface water ranged from 1597 to 12,611n/m3 and in the
      sediments was 25 to 300n/kg wet weight (ww). In the surface waters, the
      contamination was more serious in urban areas, and in the sediments, countrysides
      were the most heavily polluted areas. Fibers were the most abundant
      microplastics, the dominant color was transparent, and small-sized particles were
      predominant. Of all the microplastics identified by micro-Raman spectroscopy,
      polystyrene was the most common type (38.5%) followed by polypropylene (29.4%)
      and polyethylene (21%). Compared with low-density microplastics, the high-density
      ones were more likely to be deposited from the water into the sediment. Several
      contaminants adsorbed by microplastics, such as organic solvents and
      pharmaceutical intermediates, were observed and qualitatively analyzed by Raman
      spectroscopy. The results of this study could provide valuable background
      information for microplastic pollution in the TGR.

PMID- 29050833
TI  - Molecular manipulation of the mating-type system and development of a new
      approach for characterizing pathogen virulence in Pyrenophora tritici-repentis.
AB  - The ascomycete Pyrenophora tritici-repentis (Ptr) is an important fungal pathogen
      worldwide that causes tan spot of wheat. The fungus is self-fertile because each
      isolate contains both mating type (MAT) idiomorphs. In this work, we developed
      knockouts of the MAT genes in Ptr and tested fertility of the knockout strains
      and outcrossing between the knockout strains carrying the opposite mating type.
      The fungal strains with deletions of either MAT1-1-1 or MAT1-2-1 did not form
      mature pseudothecia making them functionally heterothallic. The cross between the
      heterothallic strains of the same isolate (86-124) was fully fertile with the
      only difference compared to the homothallic wild type strain being the slightly
      lower percentage of pseudothecium formation. However, the cross between 86-124
      (race 2, ToxA-containing isolate) and DW5 (race 5, ToxB-containing isolate) was
      partially fertile and had fewer mature pseudothecia. Furthermore, most mature
      asci produced only two or four instead of eight functional ascospores. A
      collection of ascospores from this cross was obtained and genotyped for the
      presence of the ToxA, ToxB and MAT genes as well as simple sequence repeat
      markers. The segregation of these genes and markers and recombination of
      different allele types at these loci was observed. This work clearly demonstrates
      that the fungus requires both MAT genes for sexual production and can undergo
      outcrossing and sexual recombination. It also establishes a new and practical way
      for further characterizing fungal virulence in Ptr through the development of
      segregating fungal populations and subsequent genetic analysis.

PMID- 29050834
TI  - Influence of microhabitat use and behavior of Amblyomma sculptum and Amblyomma
      dubitatum nymphs (Acari: Ixodidae) on human risk for tick exposure, with notes on
      Rickettsia infection.
AB  - Brazilian spotted fever (BSF) is a potentially lethal human disease caused by
      Rickettsia rickettsii transmitted by ticks, including Amblyomma sculptum.
      However, in Southeast Brazil, where most BSF cases occur, capybaras are key hosts
      for both A. sculptum and Amblyomma dubitatum. We therefore compared the risk of
      human exposure to these ticks at a non-endemic anthropogenic site in Southeast
      Brazil where both tick species are maintained by capybaras and occur at high
      abundance. Cloth dragging, human baits and CO2 traps were used to assess tick
      abundance and risk for human exposure. The two tick species displayed profound
      differences in behavior and microhabitat use. Notably, A. sculptum but not A.
      dubitatum quested for hosts openly from vegetation (ambush behavior) and infested
      human baits. Furthermore, A. dubitatum was more aggregated at a specific site
      whereas A. sculptum was more widespread along differing and drier microhabitats.
      Adults and nymphs of both species were infected with Rickettsia bellii. Overall,
      the results indicate that even though both species co-existed in the same area,
      A. sculptum posed a greater risk for biting humans and thus also for transmitting
      tick-borne pathogens.

PMID- 29050835
TI  - Patient handover in the emergency department: 'How' is as important as 'what'.
AB  - AIM: We explored the existing patient handover practices between emergency care
      practitioners and healthcare professionals in the emergency department. In the
      emergency department, patient handover between emergency care practitioner's and
      healthcare professionals is a complex process involving multiple functions, such
      as the transfer of information, responsibility and accountability from one person
      to another. We used a qualitative study design. Emergency care practitioners and
      healthcare professionals were identified using purposive and convenience sampling
      data. Data were collected through unstructured participant observation. We
      conducted 20 observation sessions, varying between 15 and 20min. The data were
      analysed using a creative hermeneutic approach. The 'how' or manner of patient
      handover observed between emergency care practitioners and health professionals
      was perceived as important. A diagnosis of disrespectful behaviour was made which
      could negatively influence patient handover and ultimately patient outcome.
      Disrespectful behaviour stemmed from the two signs that supported the diagnosis:
      task-orientated behaviour and the use of indigenous language. Involving the
      emergency care practitioners and healthcare professionals in observing and
      analysing the existing patient handover practices in the ED raised their
      awareness of the current workplace culture. Transforming behaviour from
      disrespectful to respectful should include greeting one another, listening
      attentively to the patient handover and include emergency care practitioners,
      patients and their significant other in the handover process that should be
      conducted in a commonly understood language. Emergency care practitioners and
      healthcare professionals should recognise that during patient handover 'how' is
      as important as 'what'.

PMID- 29050836
TI  - Emergency department nurses' experience of performing CPR in South Korea.
AB  - BACKGROUND: Emergency Department (ED) nurses often confront unexpected
      cardiopulmonary resuscitation (CPR) with little information about the patients.
      METHODS: This qualitative study explored the experience of performing CPR among
      ED nurses. Data collection took place between May and June 2016 using an online
      advertisement to recruit 17 ED nurses. Each participant was interviewed for 40
      90min. Interviews were recorded and transcribed verbatim. Data analysis was
      conducted using a conventional content-analysis method. RESULTS: Four themes
      emerged: Pressure from the urgency of the CPR, becoming sharp tempered in
      addressing personnel during CPR, keeping psychological conflicts of CPR patient
      care to oneself, and growing as an ED nurse through CPR. CONCLUSION: ED nurses
      had anxiety about CPR, regardless of their ability to perform CPR. They also
      suffered psychologically afterward. ED nurses could benefit from education that
      promotes their competencies for CPR and support systems to alleviate their
      psychological distress.

PMID- 29050837
TI  - Forensic patients in the emergency department: Who are they and how should we
      care for them?
AB  - BACKGROUND: Patients who suffer violent, crime related injuries are likely to
      seek medical assistance in emergency departments. Forensic patients may not
      disclose the cause of their injuries leading to the impairment of evidence. We
      explored healthcare providers' perceptions of forensic patients and how they
      should be cared for. METHOD: The perceptions of physicians and nurses regarding
      the profiles and care of forensic patients were explored in three urban emergency
      departments. The data were collected through a talking wall and analysed
      collaboratively, with the participants, using content analysis. RESULTS:
      Healthcare providers in emergency departments differentiated between living and
      deceased forensic patients. Healthcare providers identified living forensic
      patients as victims of sexual assault, assault, gunshots and stab wounds, and
      abused children. Deceased patients included patients that were dead on arrival or
      died in the emergency departments. Healthcare providers acknowledged that
      evidence should be collected, preserved and documented. CONCLUSION: Every trauma
      patient in the emergency department should be treated asa forensic patient until
      otherwise proven. If healthcare providers are unable to identify forensic
      patients and collect the evidence present, the patients' human right to justice
      will be violated.

PMID- 29050838
TI  - Three children of meningoencephalitis with Kikuchi necrotizing lymphadenitis.
AB  - BACKGROUND: Kikuchi necrotizing lymphadenitis (KNL) is a rare and benign cause of
      lymphadenopathy, most often cervical. The etiology of KNL remains unknown.
      Central nervous system (CNS) involvement, such as in meningoencephalitis, is a
      very rare clinical manifestation of KNL, especially in children. CASE REPORTS: A
      12-year-old boy presented with unilateral cervical lymphadenopathy and fever.
      Histopathological findings led to the diagnosis of KNL. He revisited due to
      severe headache and vomiting one week later. Cerebrospinal fluid (CSF) analysis
      demonstrated pleocytosis (lymphocytic 57%), high protein (312 mg/dL) and low
      CSF/serum glucose ratio (52/121 mg/dL.) The next day, he had a seizure. Brain MRI
      revealed increased signal involving posterior area of both hemisphere. Another 17
      year-old boy presented with headache for 7 days and behavioral and personality
      changes. He had a history of cervical lymphadenopathy two weeks ago. CSF analysis
      demonstrated lymphocytosis, high protein and low glucose ratio. MRI revealed the
      involvement of right cerebellum and posterior brainstem. A biopsy of one cervical
      lymphadenopathy demonstrated the findings of KNL. A 15-year-old girl presented
      with fever, headache, and cervical pain lasting 10 days. CSF analysis
      demonstrated pleocytosis (lymphocytic 95%), high protein and low CSF/serum
      glucose ratio. Histopathological findings of lymph node were suggestive of KNL.
      Above three patients were undertaken the steroid therapy and recovered fully
      without neurological dysfunction. CONCLUSIONS: Recognition of CNS involvement in
      KNL may help evaluate the patients of acute meningitis/encephalitis with regional
      lymphadenopathy, thereby avoiding unnecessary treatment.

PMID- 29050839
TI  - Recommendations by the Spanish Society of Rheumatology on the Use of Biological
      Therapies in Axial Spondyloarthritis.
AB  - OBJECTIVE: Recent data published on biological therapy in axial spondyloarthritis
      (axSpA) since the last publication of the recommendations of the Spanish Society
      of Rheumatology (SER) has led to the generation of a review of these
      recommendations based on the best possible evidence. These recommendations should
      be a reference for rheumatologists and those involved in the treatment of
      patients with axSpA. METHODS: Recommendations were drawn up following a nominal
      group methodology and based on systematic reviews. The level of evidence and
      grade of recommendation were classified according to the model proposed by the
      Centre for Evidence Based Medicine at Oxford. The level of agreement was
      established through the Delphi technique. RESULTS: In this review, we did an
      update of the evaluation of disease activity and treatment objectives. We
      included the new drugs with approved therapeutic indication for axSpA. We
      reviewed both the predictive factors of the therapeutic response and progression
      of radiographic damage. Finally, we drafted some recommendations for the
      treatment of patients refractory to anti-tumor necrosis factor, as well as for
      the possible optimization of biological therapy. The document also includes a
      table of recommendations and a treatment algorithm. CONCLUSIONS: We present an
      update of the SER recommendations for the use of biological therapy in patients
      with axSpA.

PMID- 29050840
TI  - Recommendations for the use of methotrexate in psoriatic arthritis.
AB  - OBJECTIVES: To develop recommendations for the management of methotrexate (MTX)
      in psoriatic arthritis (PsA), based on best evidence and experience. METHODS: A
      group of 12 experts on MTX use was selected. The coordinators formulated 14
      questions about the use of MTX in PsA patients (indications, efficacy, safety and
      cost-effectiveness). A systematic review was conducted to answer the questions.
      Using this information, inclusion and exclusion criteria were established, as
      were the search strategies (Medline, EMBASE and the Cochrane Library were
      searched). Two different reviewers selected the articles. Evidence tables were
      created. At the same time, European League Against Rheumatism and American
      College of Rheumatology abstracts were evaluated. Based on this evidence, the
      coordinators proposed 12 preliminary recommendations that the experts discussed
      and voted on in a nominal group meeting. The level of evidence and grade of
      recommendation were established using the Oxford Centre for Evidence Based
      Medicine and the level of agreement with the Delphi technique (2 rounds).
      Agreement was established if at least 80% of the experts voted yes (yes/no).
      RESULTS: A total of 12 preliminary recommendations on the use of MTX were
      proposed, 9 of which were accepted. One was included in a different
      recommendation and another 2 were not voted on and were thereafter clarified in
      the main text. CONCLUSIONS: These recommendations aim to answer frequent
      questions and help in decision making strategies when treating PsA patients with
      MTX.

PMID- 29050841
TI  - Hemothorax in vascular Ehlers-Danlos syndrome.
AB  - Vascular Ehlers-Danlos syndrome (EDS IV) is a rare genetic disorder characterized
      by an alteration in the COL3A1 gene which encodes type III collagen. It is the
      most common type of collagen in vessels of medium size and certain organs such as
      the intestines and the uterus. The alteration of this type of collagen produces
      aneurisms and ruptures of vessels and organs. A high level of clinical suspicion
      is required for diagnosis. It is a complex disease whose management requires a
      multidisciplinary team to treat the different complications that may occur. We
      report the case of a 50-year-old man diagnosed with EDS IV detected incidentally
      after hemothorax secondary to a coughing spell.

PMID- 29050842
TI  - Pseudo template molecularly imprinted polymer for determination of 14 kind of
      beta-agonists in animal urine by ultra-high-performance liquid chromatography
      tandem mass spectrometry.
AB  - A pseudo template molecularly imprinted polymer (MIP) for selective extraction of
      beta-agonists was prepared using 4-hydroxyphenethyl alcohol as pseudo template
      molecule, methyl acrylic acid as functional monomer, and ethylene glycol
      dimethacrylate as cross-linker. Selectivity and adsorption capacity of prepared
      MIP were studied in detail. MIP selectively adsorbed 14 types of beta-agonists.
      Advantages of the prepared polymer include non-template leakage in purification
      of target analytes and cheap cost. MIP was used to purify beta-agonists in urine
      samples. The developed method was combined with ultra-performance liquid
      chromatography-tandem mass spectrometry. In optimum conditions, recoveries of the
      developed method ranged from 84.2% to 109.8% with low coefficients of variation
      at below 15%. Limits of detection and quantification for 14 target beta-agonists
      in urine samples reached below 0.05ng/mL and 0.1ng/mL, respectively. The
      developed method based on MIP enrichment and purification were successfully
      applied to analysis of target analytes in 50 actual urine samples.

PMID- 29050843
TI  - Estimation of descriptors for hydrogen-bonding compounds from chromatographic and
      liquid-liquid partition measurements.
AB  - Retention factors obtained by gas chromatography and reversed-phase liquid
      chromatography on varied columns and partition constants in different liquid
      liquid partition systems are used to estimate WSU descriptor values for 36
      anilines and N-heterocyclic compounds, 13 amides and related compounds, and 45
      phenols and alcohols. These compounds are suitable for use as calibration
      compounds to characterize separation systems covering the descriptor space E=0.2
      3, S=0.4-2.1, A=0-1.5, B=0.1-1.5, L=2.5-10.0 and V=0.5-2.2. Hydrogen-bonding
      properties are discussed in terms of structure, the possibility of induction
      effects, intramolecular hydrogen bonding and steric factors for anilines, amides,
      phenols and alcohols. The relationship between these parameters and observed
      descriptor values are difficult to predict from structure but facilitate
      improving the general occupancy of the descriptor space by creating incremental
      changes in hydrogen-bonding properties. It is verified that the compounds
      included in this study can be merged with an existing database of compounds
      recommended for characterizing separation systems.

PMID- 29050844
TI  - Monitoring the corrected QT in the acute care setting: A comparison of the 12
      lead ECG and bedside monitor.
AB  - INTRODUCTION: Prolongation of the QT interval is a well-recognized complication
      associated with many commonly used medications. Emergency Department monitoring
      of the corrected QT (QTc) both before and after medication administration is
      typically performed using the 12-lead electrocardiogram (ECG). The purpose of
      this study is to compare the QTc reported on the 12-lead ECG to that reported by
      single brand of bedside monitor. METHODS: A convenience sample of emergency
      department patients over the age of 18 undergoing bedside monitoring and who had
      an ECG ordered by their treating physician were enrolled. These patients
      underwent simultaneous ECG and monitor QTc calculation. The primary outcome of
      interest was the correlation between the monitor and ECG QTc. Secondary outcomes
      included ability of each method to identify patients with a QTc >500ms and the
      ability of each method to identify patients with a QTc <450ms. RESULTS: A total
      of 125 patients had simultaneous ECG and monitor QTc measurements recorded. There
      was moderate correlation between the monitor and ECG QTc (Pearson's correlation
      coefficient=0.55). The median difference between the ECG QTc and the monitor QTc
      (ECG QTc minus monitor QTc) was -7ms (IQR -23 to 11ms). CONCLUSION: We found that
      there was moderate correlation between the QTc reported on the 12 lead ECG and
      that reported by the bedside monitor. This correlation is not strong enough to
      support the use of the bedside monitor as a substitute for the 12-lead ECG when
      evaluating a patient's QTc.

PMID- 29050845
TI  - High rate of isolated right ventricular dysfunction in patients with non
      significant CT pulmonary angiography.
AB  - BACKGROUND: Right ventricular (RV) dysfunction and pulmonary hypertension (PH)
      are commonly unrecognized in the emergency department (ED), but are associated
      with poor outcomes. Prior research has found a 30% prevalence of isolated RV
      dysfunction in ED patients after non-significant computed tomographic pulmonary
      angiography (CTPA). We aimed to prospectively define the prevalence of RV
      dysfunction and/or PH in short of breath ED patients, and assess outcomes.
      METHODS: Prospective observational study of patients with a non-significant CTPA.
      Isolated RV dysfunction and/or PH was defined as normal left ventricular function
      plus RV dilation, moderate to severe tricuspid regurgitation or RV systolic
      pressure>40mmHg on comprehensive echocardiography. RESULTS: Of 83 patients, 20
      (24%, 95% [confidence interval] CI: 16-34%) had isolated RV dysfunction and/or
      PH. These patients had 40% ED recidivism and 30% hospital readmission at 30-days.
      When compared to patients with normal echocardiographic function, they had
      significantly longer intensive care unit and hospital length of stays.
      CONCLUSIONS: In a prospective cohort of ED patients, we found a high prevalence
      of isolated RV dysfunction and/or PH after a non-significant CTPA. These patients
      had high rates of recidivism and hospital readmission. This data supports a
      continued need for ED based screening and specialty referral.

PMID- 29050846
TI  - Zika virus: what, where from and where to?
AB  - The significance of Zika virus as a clinically significant flavivirus has
      previously been under-recognised, until extensive outbreaks in Yap in 2007,
      French Polynesia in 2013 and the Americas since 2015. Although Zika virus
      infection is commonly asymptomatic or mild, emerging evidence suggests a strong
      link to microcephaly in babies and Guillain-Barre syndrome in adults. This
      article reviews the epidemiology, geographic distribution, basic virology,
      transmission, clinical presentation, potential complications, laboratory
      diagnosis, treatment and prevention of Zika virus infection. Education on
      mosquito avoidance measures and vector control efforts currently remain key to
      reducing risk of transmission, whilst further research is underway to develop
      antiviral therapies and vaccines.

PMID- 29050847
TI  - Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Presenting
      in Adulthood: a French Nationwide Retrospective Study.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital heart disease usually diagnosed during the first months of
      life. Without surgical treatment, ALCAPA carries a high mortality risk, and
      disease presentation in adulthood is rare. We describe the diagnosis and
      management of patients presenting with ALCAPA in adulthood. This multicenter
      French nationwide retrospective study included adult patients diagnosed from 1980
      to 2014. Eleven adult patients (mean age: 38 +/- 17 years) were analyzed. All
      patients were symptomatic, presenting with chest pain, palpitations, heart
      failure, or syncope. Electrocardiogram was abnormal in 8 (73%) patients.
      Echocardiogram showed a mildly depressed left ventricular ejection fraction of 50
      +/- 13%, kinetic abnormalities in 5 (45%) patients, and significant mitral
      regurgitation in 8 (73%) patients. Coronary angiography was performed in 10 (91%)
      patients and confirmed the diagnosis. Computerized tomography scan, magnetic
      resonance imaging, and myocardial scintigraphy were performed when deemed
      necessary. Ten patients underwent reconstructive surgery, but 1 patient was not
      operated because of age. Four patients experienced postoperative complications
      including cardiogenic shock, heart failure, renal failure, or additional surgery.
      After a median follow-up of 2.5 years, all 10 operated patients were alive and
      asymptomatic, and the nonoperated patient had died at the age of 70 from syncope
      related to ventricular tachycardia. ALCAPA may be diagnosed in adults. Although
      complications may occur postoperatively, long-term outcome is favorable in adult
      patients undergoing surgical correction. Surgery should be discussed as first
      line therapy in adults with ALCAPA.

PMID- 29050848
TI  - Is Metabolic Syndrome Associated with the Risk of Recurrent Stroke: A Meta
      Analysis of Cohort Studies.
AB  - BACKGROUND: The association between metabolic syndrome (MetS) and recurrence of
      stroke remains unknown. We summarized the evidence by a meta-analysis of
      prospective cohort studies. METHODS: We searched the PubMed, EMBASE, and Google
      Scholar databases from their inception until July 2016 for cohort studies
      investigating this research question; relevant information was extracted by 2
      independent investigators, and then aggregated using the random-effects meta
      analysis approach. RESULTS: We identified 5 studies, including 7752 stroke
      patients who had a history of stroke or transient ischemic attack. Compared with
      persons without MetS, persons with MetS have a significantly higher risk of
      recurrent stroke, and the pooled relative risk (RR) was 1.52 (95% confidence
      interval (CI): 1.17-1.97). The strength of this association is greater than
      individual MetS components such as elevated blood pressure (RR = 1.05, 95% CI:
      .72-1.52), elevated triglycerides (RR = 1.04, 95% CI: .84-1.29), low high-density
      lipoprotein cholesterol (RR = 1.16, 95% CI: .91-1.48), or obesity (RR = 1.12, 95%
      CI: .89-1.41). The risk of recurrent stroke was highest in the group with
      elevated glycemia (RR = 1.70, 95% CI: 1.12-2.56). CONCLUSIONS: This meta-analysis
      suggests that MetS might be an important predictor of recurrent stroke. Among the
      5 components of MetS, elevated glycemia was a stronger predictor for recurrent
      stroke.

PMID- 29050849
TI  - Neuronal and behavioral effects of multi-day brain stimulation and memory
      training.
AB  - Strategies for memory enhancement, especially for the older population, are of
      great scientific and public interest. Here, we aimed at investigating neuronal
      and behavioral effects of transcranial direct current stimulation (tDCS) paired
      with memory training. Young and older adults were trained on an object-location
      memory task on 3 consecutive days with either anodal or sham tDCS. Recall
      performance was assessed immediately after training, 1 day and 1 month later, as
      well as performance on trained function and transfer task. Resting-state
      functional magnetic resonance imaging was conducted at baseline and at 1-day
      follow-up to analyze functional coupling in the default mode network. Anodal tDCS
      led to superior recall performance after training, an associated increase in
      default mode network strength and enhanced trained function and transfer after 1
      month. Our findings suggest that tDCS-accompanied multi-day training improves
      performance on trained material, is associated with beneficial memory network
      alterations, and transfers to other memory tasks. Our study provides insight into
      tDCS-induced behavioral and neuronal alterations and will help to develop
      interventions against age-related cognitive decline.

PMID- 29050850
TI  - [Long evolution cervical tumor: Schwannoma].

PMID- 29050851
TI  - Validation of a new device to quantify groundwater-surface water exchange.
AB  - Distributions of flow across the groundwater-surface water interface should be
      expected to be as complex as the geologic deposits associated with stream or lake
      beds and their underlying aquifers. In these environments, the conventional Darcy
      based method of characterizing flow systems (near streams) has significant
      limitations, including reliance on parameters with high uncertainties (e.g.,
      hydraulic conductivity), the common use of drilled wells in the case of
      streambank investigations, and potentially lengthy measurement times for aquifer
      characterization and water level measurements. Less logistically demanding tools
      for quantifying exchanges across streambeds have been developed and include drive
      point mini-piezometers, seepage meters, and temperature profiling tools. This
      project adds to that toolbox by introducing the Streambed Point Velocity Probe
      (SBPVP), a reusable tool designed to quantify groundwater-surface water
      interactions (GWSWI) at the interface with high density sampling, which can
      effectively, rapidly, and accurately complement conventional methods. The SBPVP
      is a direct push device that measures in situ water velocities at the GWSWI with
      a small-scale tracer test on the probe surface. Tracer tests do not rely on
      hydraulic conductivity or gradient information, nor do they require long
      equilibration times. Laboratory testing indicated that the SBPVP has an average
      accuracy of +/-3% and an average precision of +/-2%. Preliminary field testing,
      conducted in the Grindsted A in Jutland, Denmark, yielded promising agreement
      between groundwater fluxes determined by conventional methods and those estimated
      from the SBPVP tests executed at similar scales. These results suggest the SBPVP
      is a viable tool to quantify groundwater-surface water interactions in high
      definition in sandy streambeds.

PMID- 29050852
TI  - Coop-Seq Analysis Demonstrates that Sox2 Evokes Latent Specificities in the DNA
      Recognition by Pax6.
AB  - Sox2 and Pax6 co-regulate genes in neural lineages and the lens by forming a
      ternary complex likely facilitated allosterically through DNA. We used the
      quantitative and scalable cooperativity-by-sequencing (Coop-seq) approach to
      interrogate Sox2/Pax6 dimerization on a DNA library where five positions of the
      Pax6 half-site were randomized yielding 1024 cooperativity factors. Consensus
      positions normally required for the high-affinity DNA binding by Pax6 need to be
      mutated for effective dimerization with Sox2. Out of the five randomized bases, a
      5' thymidine is present in most of the top ranking elements. However, this
      thymidine maps to a region outside of the Pax half site and is not expected to
      directly interact with Pax6 in known binding modes suggesting structural
      reconfigurations. Re-analysis of ChIP-seq data identified several genomic regions
      where the cooperativity promoting sequence pattern is co-bound by Sox2 and Pax6.
      A highly conserved Sox2/Pax6 bound site near the Sprouty2 locus was verified to
      promote cooperative dimerization designating Sprouty2 as a potential target
      reliant on Sox2/Pax6 cooperativity in several neural cell types. Collectively,
      the functional interplay of Sox2 and Pax6 demands the relaxation of high-affinity
      binding sites and is enabled by alternative DNA sequences. We conclude that this
      binding mode evolved to warrant that a subset of target genes is only regulated
      in the presence of suitable partner factors.

PMID- 29050853
TI  - Cytoplasmic expression of CD133 stemness marker is associated with tumor
      aggressiveness in clear cell renal cell carcinoma.
AB  - Prominin-1 (CD133) is one of the most commonly used markers for cancer stem cells
      (CSCs), which are characterized by their ability for self-renewal and
      tumorigenicity. However, the clinical and prognostic significance of CSCs in
      renal cell carcinoma (RCC) remains unclear. The aim of this study was to
      investigate the expression patterns and prognostic significance of the cancer
      stem cell marker CD133 in different histological subtypes of RCC. CD133
      expression was evaluated using immunohistochemistry in 193 well-defined renal
      tumor samples on tissue microarrays, including 136 (70.5%) clear cell renal cell
      carcinomas (CCRCCs), 26 (13.5%) papillary RCCs, and 31 (16.1%) chromophobe RCCs.
      The association between CD133 expression and clinicopathological features as well
      as the survival outcomes was determined. There was a statistically significant
      difference between CD133 expression among the different RCC subtypes. In CCRCC,
      higher cytoplasmic expression of CD133 was significantly associated with increase
      in grade, stage, microvascular invasion (MVI) and lymph node invasion (LNI),
      while no association was found with the membranous expression. Moreover, on
      multivariate analysis, TNM stage and nuclear grade were independent prognostic
      factors for overall survival (OS) in cytoplasmic expression. We showed that
      higher cytoplasmic CD133 expression was associated with more aggressive tumor
      behavior and more advanced disease in CCRCC but not in the other examined
      subtypes. Our results demonstrated that higher cytoplasmic CD133 expression is
      clinically significant in CCRCC and is associated with increased tumor
      aggressiveness and is useful for predicting cancer progression.

PMID- 29050855
TI  - Response to Ricketts DM et al: Physiotherapy versus home exercises after
      hydrodilatation.

PMID- 29050854
TI  - Pretransplantation Portal Vein Recanalization and Transjugular Intrahepatic
      Portosystemic Shunt Creation for Chronic Portal Vein Thrombosis: Final Analysis
      of a 61-Patient Cohort.
AB  - PURPOSE: To report the final analysis of the safety and efficacy of portal vein
      (PV) recanalization (PVR) and transjugular intrahepatic portosystemic shunt
      (TIPS) creation (PVR-TIPS) in patients with PV thrombosis (PVT) in need of liver
      transplantation. MATERIALS AND METHODS: Sixty-one patients with cirrhosis and PVT
      underwent PVR-TIPS to improve transplantation candidacy. Median patient age was
      58 years (range, 22-75 y), and median pre-TIPS Model for End-Stage Liver Disease
      score was 14 (range, 7-42). The most common etiologies of cirrhosis were
      nonalcoholic fatty liver disease in 18 patients (30%) and hepatitis C in 13
      patients (21%). Twenty-seven patients (44%) had partial PVT, and 34 patients
      (56%) had complete thrombosis. Forty-nine patients (80%) had Yerdel grade 2 PVT,
      and 12 (20%) had Yerdel grade 3 PVT. Twenty-nine patients (48%) had cavernous
      transformation of the PV. RESULTS: PVR-TIPS was technically successful in 60 of
      61 patients (98%). PV/TIPS patency was maintained in 55 patients (92%) at a
      median follow-up of 19.2 months (range, 0-105.9 mo). Recurrent PV/TIPS thrombosis
      occurred in 5 patients (8%), all of whom initially presented with complete PVT.
      The most common adverse events were TIPS stenosis in 13 patients (22%) and
      transient encephalopathy in 11 patients (18%). Twenty-four patients (39%)
      underwent transplantation, 23 of whom (96%) received an end-to-end anastomosis.
      There were no cases of recurrent PVT following transplantation, with a median
      imaging follow-up of 32.5 months (range, 0.4-75.4 mo). Five-year overall survival
      rate was 82%. CONCLUSIONS: PVR-TIPS is a safe, effective, and durable treatment
      option for patients with chronic PVT who need liver transplantation.

PMID- 29050857
TI  - Corrections.

PMID- 29050856
TI  - The relationship between age, rotator cuff integrity, and osseous
      microarchitecture of greater tuberosity: Where should we put anchor?
AB  - OBJECTIVE: The aim of this study was to compare the microarchitecture of the
      greater tuberosity with or without rotator cuff tear and to obtain optimum
      location for anchor screw insertion for rotator cuff repair. METHODS: Twenty-five
      humeral heads were harvested from 13 male cadavers of mean age 58.4 years,
      including 6 humeri with rotator cuff tear and 19 intact humeri. Six regions of
      interest (proximal, intermediate, and distal zones of the superficial and deep
      regions) were divided into the anterior (G1), middle (G2), and posterior (G3)
      areas of the greater tuberosity. Trabecular bone volume and cortical thickness
      were evaluated. RESULTS: Total trabecular bone volume was greater in subjects <50
      years old than in subjects >50 years old but did not differ significantly in
      subjects with and without rotator cuff tear. Cortical thickness in both intact
      and torn rotator cuff groups was significantly greater in the proximal and
      intermediate zones than in the distal zone. Cortical thickness was related to
      anatomic location rather than age or cuff tear. CONCLUSION: The optimal location
      for anchor screw insertion during rotator cuff repair is either the proximal or
      intermediate region of the greater tuberosity. Age has more influence in terms of
      trabecular bone volume loss than rotator cuff integrity.

PMID- 29050858
TI  - The inframammary skin-sparing mastectomy technique.
AB  - Skin-sparing mastectomy and immediate implant-based breast reconstruction is
      technically a challenging procedures for women with large, ptotic breasts. This
      is usually performed using the Wise pattern incision resulting in an inverted T
      scar, which is associated with postoperative complications. The other challenge
      is obtaining adequate coverage of the prosthesis. We describe a technique that
      avoids the inverted T scar and provides a single horizontal scar with a double
      dermo-muscular layer coverage of the prosthesis.

PMID- 29050859
TI  - Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the
      APP/PS1 transgenic mouse model of Alzheimer's disease.
AB  - Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD).
      Previous studies have shown that the incretin hormones glucagon-like peptide-1
      (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) that have anti
      diabetic properties show very promising effects in animal models of AD. Glucagon
      (Gcg) is a hormone and growth-factor, and the Gcg receptor is expressed in the
      brain. Here we test the effects of a triple receptor agonist (TA), which
      activates GIP-1, GIP and glucagon receptors at the same time. In the present
      study, the effects of the TA were evaluated in the APP/PS1 transgenic mouse model
      of AD. The TA was injected once-daily (10 nmol/kg i.p.) for two months. The
      results showed that treatment with TA significantly reversed the memory deficit
      in the APP/PS1 mice in a spatial water maze test. Moreover, the drug reduced
      levels of the mitochondrial pro-apoptotic signaling molecule BAX, increased the
      anti-apoptotic signaling molecule Bcl-2 and enhanced the levels of BDNF, a key
      growth factor that protects synaptic function. Levels of synaptophysin were
      enhanced, demonstrating protection from synaptic loss that is observed in AD.
      Neurogenesis in the dentate gyrus was furthermore enhanced as shown in the
      increase of doublecortin positive cells. Furthermore, TA treatment reduced the
      total amount of beta-amyloid, reduced neuroinflammation (activated microglia and
      astrocytes), and oxidative stress in the cortex and hippocampus. Thus, these
      findings show that novel TAs are a promising lead for the design of future
      treatment strategies in AD.

PMID- 29050860
TI  - EEG power spectrum maturation in preterm fetal growth restricted infants.
AB  - Power spectral analysis of the electroencephalogram (EEG) is a non-invasive
      method to examine infant brain maturation. Preterm fetal growth restricted (p
      FGR) neonates display an altered EEG power spectrum compared to appropriate-for
      gestational-age (AGA) peers, suggesting delayed brain maturation. Longitudinal
      studies investigating EEG power spectrum maturation in p-FGR infants are lacking,
      however. We thus aimed to investigate brain maturation using sleep EEG power
      spectral analysis in p-FGR infants compared to preterm and term AGA controls (p
      AGA and t-AGA, respectively). EEG was recorded during spontaneous sleep in 13 p
      FGR, 17 p-AGA and 19 t-AGA infants at 1 and 6 months post-term age. Infant sleep
      states (active and quiet sleep) were scored using standard criteria. Power
      spectral analysis of a single-channel EEG (C3-M2/C4-M1) was performed using Fast
      Fourier Transform. The EEG power spectrum was divided into delta (0.5-4 Hz),
      theta (4-8 Hz), alpha (8-12 Hz), sigma (12-14 Hz) and beta (14-30 Hz) frequency
      bands. Relative (%) powers and the spectral edge frequency were calculated. The
      spectral edge frequency was significantly higher in p-FGR infants compared to p
      AGA controls in quiet sleep at 1 month post-term age (p < .01). This was due to
      significantly reduced %-delta and significantly increased %-theta, %-alpha and %
      beta power (p < .01 for all) compared to p-AGA infants. p-FGR infants also showed
      significantly increased %-beta power compared to t-AGA infants (p < .05). No
      group differences were observed in active sleep or at 6 months post-term age. In
      conclusion, p-FGR infants show altered sleep EEG power spectrum maturation
      compared to AGA peers. However, changes resolved by 6 months post-term age.

PMID- 29050861
TI  - An appropriate mean arterial pressure (MAP) does not always mean hemodynamic
      stability in septic shock patients.

PMID- 29050862
TI  - JAK/STAT signaling pathway gene expression is reduced following Nelf knockdown in
      GnRH neurons.
AB  - Hypothalamic gonadotropin releasing hormone (GnRH) is crucial for the proper
      function of the hypothalamic-pituitary-gonadal (HPG) axis, subsequent puberty,
      and reproduction. When GnRH neuron migration or GnRH regulation is impaired,
      hypogonadotropic hypogonadism results. Mutations in the gene for nasal embryonic
      luteinizing hormone-releasing factor (NELF) have been identified in GnRH
      deficient humans. NELF is a predominantly nuclear protein that may participate in
      gene transcription, but the genes NELF regulates are unknown. To address this
      question, RNA was extracted from NLT GnRH neuronal cells following either stable
      Nelf knockdown or scrambled control and subjected to cDNA arrays. Transcription
      factors and cell migration gene expression was altered most commonly. Members of
      the Janus kinase/signal transducers and activators of transcription (JAK/STAT)
      pathway, including Stat1, Stat2, Stat5a, Jak2, Irf7 and Irf9, were significantly
      down regulated as assessed by RT-qPCR. Protein levels of STAT1, phospho-STAT1,
      and JAK2 were reduced, but the protein level of phospho-JAK2 was not. These
      findings suggest a role for NELF in the regulation of the JAK/STAT signaling
      pathway, which have important functions in GnRH neurons.

PMID- 29050863
TI  - [Intravenous immunoglobulin therapy in non-menstrual staphylococcal toxic shock
      syndrome].

PMID- 29050864
TI  - Outpatient parenteral antibiotic therapy: Evaluation of practices and limits of
      use in rural areas in France.
AB  - OBJECTIVES: To evaluate outpatient parenteral antibiotic therapy (OPAT) practices
      in a French rural area. MATERIAL AND METHODS: Descriptive study assessing
      knowledge, practices, and limitations of OPAT use among hospital practitioners
      (HP), family physicians (FP), and private nurses (PN). RESULTS: OPAT (mainly
      ceftriaxone and penicillins) was used by 69.6%, 73.3%, and 97.7% of the 23 HPs,
      45 FPs, and 46 PNs mostly for respiratory or urinary tract infections,
      bacteremia, and/or multidrug-resistant bacterial infections. Overall, 65.2% of
      HPs and 37.8% of FPs were in contact with an infectious disease specialist.
      Knowledge of OPAT benefits and risks was lower for FPs than HPs. The main
      obstacles were the patient's geographic isolation (HPs), the availability of a
      venous catheter, the lack of training (FPs), and the expected OPAT-associated
      overwork (PNs). CONCLUSION: OPAT practice is weak in rural areas. Declared
      obstacles constitute fields of improvement for its essential expansion.

PMID- 29050865
TI  - Chloride-enhanced oxidation of organic contaminants by Cu(II)-catalyzed Fenton
      like reaction at neutral pH.
AB  - The Cu(II)-catalyzed Fenton-like reaction was found to be significantly
      accelerated in the presence of chloride ion (i.e., the Cu(II)/H2O2/Cl- system),
      enhancing the oxidative degradation of organic contaminants at neutral pH. The
      degradation of carbamazepine (a select target contaminant) by the Cu(II)/H2O2
      system using 1MUM Cu(II) and 10mM H2O2 was accelerated by 28-fold in the presence
      of 10,000mg/L Cl- at pH 7. The observed rate of carbamazepine degradation
      generally increased with increasing doses of Cu(II), H2O2, and Cl-, and exhibited
      an optimal value at around pH 7.5. Various other organic contaminants such as
      propranolol, phenol, acetaminophen, 4-chlorophenol, benzoic acid, and caffeine
      were also effectively degraded by the Cu(II)/H2O2/Cl- system. Experiments using
      oxidant probe compounds and electron paramagnetic spectroscopy suggested that
      cupryl (Cu(III)) species are the major reactive oxidants responsible for the
      degradation of these organic contaminants. The enhanced kinetics was further
      confirmed in natural seawater.

PMID- 29050866
TI  - Seizure semiology in leucine-rich glioma-inactivated protein 1 antibody
      associated limbic encephalitis.
AB  - OBJECTIVE: The objective of this study was to advance the characterization of
      seizure semiology in leucine-rich glioma-inactivated protein 1 (LGI1) antibody
      associated limbic encephalitis (LE). METHODS: Eighteen patients diagnosed with
      LGI1 LE were identified. Seizure semiology, demographic features, MRI and
      fluorodeoxyglucose positron emission tomography (FDG-PET), electroencephalograms,
      and outcomes following immunotherapy were evaluated. RESULTS: Patients were
      divided into the following groups based on seizure semiology: faciobrachial
      dystonic seizure only (FBDS-only, n=4), epileptic seizure without FBDS (Non-FBDS,
      n=6), and FBDS plus epileptic seizure (FBDS+, n=8). In the group with Non-FBDS,
      the majority of patients (5/6) manifested mesial temporal lobe epilepsy (MTLE)
      like semiology (i.e., fear, epigastric rising, staring, and automatisms) with a
      frequency of 7+/-5 times per day and a duration of 15.3+/-14.3s. In the group
      with FBDS+, the distinctive symptom was FBDS followed by epileptic events,
      especially automatisms (7/8), with a frequency of 16+/-12 times per day and a
      duration of 13.0+/-8.0s. In these cases, 67% and 50% of the patients showed
      abnormalities on MRI and FDG-PET, respectively, and the mesial temporal lobe
      structures were most often involved. Ictal discharges were observed in 0/4, 6/6,
      and 8/8 of the patients in the groups with FBDS only, Non-FBDS, and FBDS+,
      respectively. The temporal lobe was mainly affected. Immunotherapy had favorable
      therapeutic effects. SIGNIFICANCE: The LGI1 LE should be considered as one
      disease syndrome with a series of clinical manifestation. Identifying types of
      unique semiology features will facilitate the early diagnosis and the timely
      initiation of immunotherapy.

PMID- 29050867
TI  - Acute type A aortic dissection in a patient with paraganglioma.
AB  - Acute aortic dissection is the most common acute aortic syndrome. It is more
      prevalent in males and in the elderly, and has a high mortality. Hypertension is
      the main risk factor. Diagnosis is based on clinical features, laboratory tests
      and imaging exams. Treatment is usually surgical, although in some cases an
      endovascular approach is an alternative. Paraganglioma is an uncommon
      neuroendocrine tumor. Most produce catecholamines, and so usually manifest with
      hypertensive crisis, palpitations, headache and sweating. This tumor is diagnosed
      by measurement of plasma or urinary catecholamines and by computed tomography,
      magnetic resonance imaging and 123I-metaiodobenzylguanidine (MIBG) scintigraphy.
      Surgery is the only potentially curative treatment.

PMID- 29050868
TI  - A peripheral comment.

PMID- 29050869
TI  - Parameters influencing the physical activity of patients with a history of
      coronary revascularization.
AB  - INTRODUCTION AND OBJECTIVE: Coronary artery disease is the leading cause of
      mortality worldwide. Regular physical activity is part of a comprehensive
      management strategy for these patients. We investigated the parameters that
      influence physical activity in patients with a history of coronary
      revascularization. METHODS: We included outpatients with a history of coronary
      revascularization at least six months prior to enrollment. Data on physical
      activity, demographics, and clinical characteristics were collected via a
      questionnaire. RESULTS: A total of 202 consecutive outpatients (age 61.3+/-11.2
      years, 73% male) were enrolled. One hundred and four (51%) patients had previous
      percutaneous coronary intervention, 67 (33%) had coronary bypass graft surgery,
      and 31 (15%) had both procedures. Only 46 patients (23%) engaged in regular
      physical activity. Patients were classified into two subgroups according to their
      physical activity. There were no significant differences between subgroups in
      terms of age, comorbid conditions or revascularization type. Multivariate
      regression analysis revealed that low education level (OR=3.26, 95% CI: 1.31
      8.11, p=0.01), and lack of regular follow-up (OR=2.95, 95% CI: 1.01-8.61, p=0.04)
      were independent predictors of non-adherence to regular physical activity among
      study subjects. CONCLUSIONS: Regular exercise rates were lower in outpatients
      with previous coronary revascularization. Education level and regular follow-up
      visits were associated with adherence to physical activity in these patients.

PMID- 29050870
TI  - Brugada syndrome is associated with scar and endocardial involvement: Insights
      from high-density mapping with the RhythmiaTM mapping system.
AB  - The authors report the first catheter ablation of Brugada syndrome in the
      literature using the RhythmiaTM mapping system. Learning points include: (1) low
      voltage areas can be documented while mapping in some individuals, suggesting
      that Brugada syndrome may not be a pure ion channel disorder; (2) typical long
      fractionated potentials can also be identified in the endocardium, supporting the
      need to map the endocardium in all Brugada patients requiring ablation; (3)
      disappearance of the typical coved pattern following ablation does not
      necessarily predict cure, as the patient we present experienced ventricular
      fibrillation recurrence a few months later.

PMID- 29050871
TI  - Idiopathic inferior vena cava aneurysm - tomographic diagnosis.

PMID- 29050873
TI  - Comparing the sensation of common donor site regions for autologous breast
      reconstruction to that of a healthy breast.
AB  - INTRODUCTION: Autologous breast reconstruction has become the standard care for
      breast cancer patients. Although excellent cosmetic results can be achieved, most
      reconstructed breasts fail to regain normal sensation. Nerve coaptation of the
      flap has been suggested to improve sensation; the effect of the donor flap native
      sensory threshold on the degree of sensory restoration is yet to be determined.
      The aim of this study is to evaluate the differences in sensation between various
      potential donor site regions in comparison to the sensation of the healthy
      breast. PATIENTS AND METHODS: A cross-sectional study in healthy women was
      performed in the Maastricht University Medical Centre. Monofilaments were used to
      measure sensation in the breast and at different flap donor sites: deep inferior
      epigastric perforator (DIEP), lateral thigh perforator (LTP), profunda artery
      perforator (PAP), superior gluteal artery perforator (SGAP) and transverse
      musculocutaneous gracilis (TMG) flaps. The Wilcoxon signed rank test was used to
      analyse statistical significance in sensation. RESULTS: Fifty women with a mean
      age of 49 +/- 2.72 years and mean BMI of 26.14 +/- 0.89 kg/m2 were included in
      the study. The median monofilament value of the normal breasts was 2.97(2.56
      3.55). The median monofilament value of each donor site and p value when compared
      to the healthy breast were as follows: DIEP flap, 2.62 (2.36-3.22) p < 0.01; LTP
      flap, 3.61 (2.83-4.08) p <0.01; PAP flap, 3.09 (2.67-3.5) p = 0.97; SGAP flap,
      3.22 (2.64-3.87) p = 0.01; and TMG flap, 3.03 (2.6-3.47) p = 0.69. CONCLUSIONS:
      There is a significant difference in sensation between the various donor site
      regions for breast reconstruction and the healthy breast. This may be taken into
      consideration for donor site selection.

PMID- 29050874
TI  - Plastic surgical operative workload in major trauma centres (POW-MTC): A UK
      prospective national cohort study.

PMID- 29050872
TI  - MANF Promotes Differentiation and Migration of Neural Progenitor Cells with
      Potential Neural Regenerative Effects in Stroke.
AB  - Cerebral ischemia activates endogenous reparative processes, such as increased
      proliferation of neural stem cells (NSCs) in the subventricular zone (SVZ) and
      migration of neural progenitor cells (NPCs) toward the ischemic area. However,
      this reparative process is limited because most of the NPCs die shortly after
      injury or are unable to arrive at the infarct boundary. In this study, we
      demonstrate for the first time that endogenous mesencephalic astrocyte-derived
      neurotrophic factor (MANF) protects NSCs against oxygen-glucose-deprivation
      induced injury and has a crucial role in regulating NPC migration. In NSC
      cultures, MANF protein administration did not affect growth of cells but
      triggered neuronal and glial differentiation, followed by activation of STAT3. In
      SVZ explants, MANF overexpression facilitated cell migration and activated the
      STAT3 and ERK1/2 pathway. Using a rat model of cortical stroke,
      intracerebroventricular injections of MANF did not affect cell proliferation in
      the SVZ, but promoted migration of doublecortin (DCX)+ cells toward the corpus
      callosum and infarct boundary on day 14 post-stroke. Long-term infusion of MANF
      into the peri-infarct zone increased the recruitment of DCX+ cells in the infarct
      area. In conclusion, our data demonstrate a neuroregenerative activity of MANF
      that facilitates differentiation and migration of NPCs, thereby increasing
      recruitment of neuroblasts in stroke cortex.

PMID- 29050875
TI  - Subcutaneous mastectomy in female-to-male transsexuals: Optimizing perioperative
      and operative management in 8 years clinical experience.
AB  - INTRODUCTION: The incidence of complications, especially acute hematoma requiring
      surgical revision in female-to-male transsexuals (FTMTS), is consistently highly
      documented in literature with up to 33%. Since 2008 we perform subcutaneous
      mastectomies in FTMTS with an annually increasing number of cases. Due to an
      initially high hematoma revision rate in the previously published cohort (2008
      2013), we implemented peri- and postoperative preventive measures and compared
      the results with the recent patient cohort (2014-2016). PATIENTS AND METHODS: The
      records of 356 patients (712 mastectomies) were retrospectively reviewed. We
      compared the first cohort (C1, 01/2008 - 12/2013, 346 mastectomies; peri- and
      postoperative standard procedure and implementation of an algorithmic care path
      in our institution) with the recent cohort (C2, 01/2014 - 01/2016, 366
      mastectomies) and introduced in C2 the following preventive measures:
      perioperative administration of tranexamic acid, intraoperative elevation of
      blood pressure to at least 120 mmHg before wound closure, bedrest and consequent
      wearing of compression bandage without removal 12 hours postoperatively.
      Comparison of complication rate, patient satisfaction and secondary revision rate
      was obtained in both cohorts. RESULTS: The mean operation time could be reduced
      from 103.6 minutes to 72.5 minutes (p < 0.05). The overall complication rate
      could be diminished from 11.8% to 5.5% (p < 0.05), the acute hematoma revision
      rate from 9.2% to 4.1% (p < 0.05). Secondary revisions were similar in both
      patient cohorts. Patient satisfaction rate was ameliorated from 88% to 93.5%
      "very satisfied" to "satisfied" patients. CONCLUSION: Hematoma is the most common
      reason for reoperation in FTMTS patients. By implementation of peri- and
      postoperative preventive measures and additional application of an algorithmic
      care path we could achieve a significant reduction of complications, particularly
      of the hematoma evacuation rate. During 8 years clinical and operative treatment
      in FTMTS we could furthermore achieve a decrease in operative time and an
      ameliorated patient satisfaction with the aesthetic results.

PMID- 29050876
TI  - Comparative genomic analysis of Clostridium acetobutylicum for understanding the
      mutations contributing to enhanced butanol tolerance and production.
AB  - Clostridium acetobutylicum JB200 is a hyper butanol tolerant and producing strain
      obtained from asporogenic C. acetobutylicum ATCC 55025 through mutagenesis and
      adaptation in a fibrous bed bioreactor. The complete genomes of both strains were
      sequenced by the Illumina Hiseq2000 technology and assembled using SOAPdenovo
      approach. Compared to the genomic sequence of the type strain ATCC 824, 143
      single nucleotide polymorphisms (SNPs) and 17 insertion/deletion variations
      (InDels) were identified in the genome of ATCC 55025. Twenty-nine mutations were
      in genes involved in sporulation, solventogenesis and stress response. Compared
      to ATCC 55025, there were seven additional point mutations in the chromosome of
      JB200. Among them, a single-base deletion in cac3319 encoding an orphan histidine
      kinase caused protein C-terminal truncation. Disruption of this gene in ATCC
      55025 and ATCC 824 resulted in significantly elevated butanol tolerance and
      production. This study provides genome-level information for the better
      understanding of solventogenic C. acetobutylicum in several key aspects of cell
      physiology and metabolism, which could help further metabolic engineering of
      Clostridium for butanol production.

PMID- 29050877
TI  - Diacylglycerol acyltransferase 2 of Mortierella alpina with specificity on long
      chain polyunsaturated fatty acids: A potential tool for reconstituting lipids
      with nutritional value.
AB  - Based on available genome sequences and bioinformatics tools, we searched for an
      uncharacterized open reading frame of Mortierella alpina (MaDGAT2) using
      diacylglycerol acyltransferase sequence (fungal DGAT type 2B) as a query.
      Functional characterization of the identified native and codon-optimized M.
      alpina genes were then performed by heterologous expression in Saccharomyces
      cerevisiae strain defective in synthesis of neutral lipid (NL). Lipid analysis of
      the yeast tranformant carrying MaDGAT2 showed that the NL biosynthesis and lipid
      particle formation were restored by the gene complementation. Substrate
      specificity study of the fungal enzyme by fatty acid supplementation in the
      transformant cultures showed that it had a broad specificity on saturated and
      unsaturated fatty acid substrates for esterification into triacylglycerol (TAG).
      The n-6 polyunsaturated fatty acids (PUFAs) with 18 and 20 carbon atoms,
      including linoleic acid, gamma-linolenic acid, dihomo gamma-linolenic and
      arachidonic acid could be incorporated into TAG fraction in the yeast cells.
      Interestingly, among n-3 PUFAs tested, the MaDGAT2 enzyme preferred
      eicosapentaenoic acid (EPA) substrate as its highly proportional constituent
      found in TAG fraction. This study provides a potential genetic tool for
      reconstituting oils rich in long-chain PUFAs with nutritional value.

PMID- 29050878
TI  - Stable symbiotic nitrogen fixation under water-deficit field conditions by a
      stress-tolerant alfalfa microsymbiont and its complete genome sequence.
AB  - We here characterized the stress-tolerant alfalfa microsymbiont Sinorhizobium
      meliloti B401. B401-treated plants showed high nitrogen fixation rates under
      humid and semiarid environments. The production of glycine betaine in isolated
      bacteroids positively correlated with low precipitation levels, suggesting that
      this compound acts as a critical osmoprotectant under field conditions. Genome
      analysis revealed that strain B401 contains alternative pathways for the
      biosynthesis and uptake of glycine betaine and its precursors. Such genomic
      information will offer substantial insight into the environmental physiology of
      this biotechnologically valuable nitrogen-fixing bacterium.

PMID- 29050879
TI  - One-pot synthesis of GDP-l-fucose by a four-enzyme cascade expressed in
      Lactococcus lactis.
AB  - GDP-l-fucose is an l-fucose donor to synthesize fucosylated compounds such as
      human milk oligosaccharides or Lewis antigen. In this study, we used Lactococcus
      lactis subsp. cremoris NZ9000 to express 4 enzymes, ManB, ManC, Gmd, and WcaG and
      produced GDP-l-fucose by using one-pot synthesis method with mannose-6-phosphate
      as substrate and the enzymes as biocatalyst. For preparation of enzyme mixture, 4
      genes (manB, manC, gmd, and wcaG) cloned from Escherichia coli were transformed
      into L. lactis strains using pNZ8008 and the recombinant cell lysates were
      obtained after cultivation. When mannose-6-phosphate was used as the substrate,
      the consecutive reactions with ManB, ManC, Gmd, and WcaG resulted in the
      successful production of GDP-l-fucose (0.13mM). When GDP-d-mannose was used as
      the substrate, it was entirely converted to GDP-l-fucose (0.2mM; 0.12g/L) via 2
      enzymatic reactions mediated by Gmd and WcaG. This is the first report of GDP-l
      fucose production by using multiple enzymes expressed in lactic acid bacteria.

PMID- 29050880
TI  - A Novel Method for Enhancing Strains' Biodegradation of 4-Chloronitrobenzene.
AB  - This paper introduces a novel approach to enhance the strains' biodegradation of
      4-chloronitrobenzene by utilizing the synergistic effect of the organic reductant
      mannitol and the substrate beef extraction. Our results demonstrate that 4
      chloronitrobenzene could not be an available nitrogen source to support target
      strains' growth, which induced the limited 4-chloronitrobenzene biodegradation.
      In addition, the organic reducing agent and substrate had a better synergistic
      effect than inorganic reducing agent and substrate to enhance the strains' 4
      chloronitrobenzene cometabolic biodegradation. Employing the synergistic effect
      of the optimal mixture (mannitol and beef extraction), the biodegradation rates
      of 50mgL-1 4-chloronitrobenzene by seven of the ten target strains were enhanced
      up to 100% from previous removals of no more than 19.1% after 7days. Three of the
      strains could even completely degrade 100mgL-1 4-chloronitrobenzene while five
      strains degraded over 91.4%. The method has good potential to enhance
      bioremediation of various 4-Chloronitrobenzene-contaminated environments as
      mannitol and beef extraction are non-toxic to the environment.

PMID- 29050881
TI  - Development of a microbial test suite and data integration method for assessing
      microbial health of contaminated soil.
AB  - There is no standard methodology or guideline for assessing soil microbial health
      for the purposes of contaminant risk assessments. Here we propose a laboratory
      based test suite and novel data integration method for evaluating soil microbial
      health using site-specific contaminated and reference soil. The test suite
      encompasses experiments for evaluating microbial biomass, activity, and
      diversity. The results from the tests are then integrated so that a Soil
      Microbial Health Score (SMHS) may be assigned. This test suite and data
      integration method was tested on soils from 3 different contaminated sites in
      Canada. The soil microbial health of a petroleum hydrocarbon (PHC) contaminated
      site was found to be 'Mildly Impacted' and 'Moderately Impacted' for two soil
      horizons at a boreal forest site. The soil microbial health of the mixed
      metal/PHC and mixed metal sites were both found to be 'Not Impacted'. Continued
      use of this test suite and data integration method will help create guidelines
      for assessing soil microbial health in ecological risk assessments.

PMID- 29050882
TI  - Surface Glycans: A Therapeutic Opportunity for Kinetoplastid Diseases: (Trends in
      Parasitology 2017).

PMID- 29050883
TI  - Evaluation of antimicrobial potential of successive extracts of Ulmus wallichiana
      Planch.
AB  - BACKGROUND: The plant Ulmus wallichiana Planch. is found in hills of Uttarakhand,
      India. Bark of U. wallichiana is commonly used as traditional healer for bone
      fracture of animals as well as human beings and also used as wound healer remedy.
      OBJECTIVE: The present study was designed to evaluate antimicrobial potential of
      various extracts of U. wallichiana bark. MATERIALS AND METHODS: Soxhlet
      extraction method was used for preparation of different extracts viz. petroleum
      ether, chloroform, ethyl acetate, ethanol and aqueous. Antioxidant activity was
      determined by DPPH and FRAP assay method. In vitro antimicrobial activity was
      evaluated using agar well diffusion method. RESULTS: Ethyl acetate extract
      exhibited the highest significant antioxidant activity. Antibacterial activity
      was performed against Escherichia coli, Bacillus subtilis, Staphylococcusaureus
      and Pseudomonas aeruginosa. Amongst the various extracts tested, only ethyl
      acetate exhibited highest zone of inhibition as compared to other extracts and
      greater than standard drug. Chloroform extract also showed moderate zone of
      inhibition. Antifungal activity was evaluated against Aspergillus fumigates and
      Aspergillus flavus. The ethyl acetate extract showed maximum zone of inhibition
      as compared to other extracts. Chloroform extract showed mild antifungal
      activity. Chloramphenicol and nystatin were used as a positive control as
      antibacterial and antifungal agent respectively. Furthermore, the highest
      percentage of phenolic and flavonoid compounds was estimated in ethyl acetate
      extract. CONCLUSION: The ethyl acetate extract of U. wallichiana showed the
      highest antimicrobial activity, and should be further investigated for isolating
      active compound(s) responsible for antimicrobial activity.

PMID- 29050884
TI  - Initial digital vasculitis in a large multicenter cohort of childhood-onset
      systemic lupus erythematosus.
AB  - OBJECTIVES: To assess clinical digital vasculitis (DV) as an initial
      manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a
      large population. METHODS: Multicenter cross-sectional study including 852 cSLE
      patients (ACR criteria) followed in ten Pediatric Rheumatology centers in Sao
      Paulo State, Brazil. RESULTS: DV was observed in 25/852 (3%) cSLE patients.
      Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7
      (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene
      in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%).
      Comparison of patients with and without DV revealed higher frequency of malar
      rash (80% vs. 53%, p=0.008), discoid rash (16% vs. 4%, p=0.017), photosensitivity
      (76% vs. 45%, p=0.002) and other cutaneous vasculitides (80% vs. 19%, p<0.0001),
      whereas the frequency of overall constitutional features (32% vs. 61%, p=0.003),
      fever (32% vs. 56%, p=0.020) and hepatomegaly (4% vs. 23%, p=0.026) were lower in
      these patients. Frequency of female gender, severe multi-organ involvement,
      autoantibodies profile and low complement were alike in both groups (p>0.05).
      SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients
      with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58),
      p=0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The
      frequency of cyclophosphamide use (0% vs. 18%, p=0.014) was significantly lower
      in the DV group. CONCLUSION: Our large multicenter study identified clinical DV
      as one of the rare initial manifestation of active cSLE associated with a mild
      multisystemic disease, in spite of digital resorption in some of these patients.

PMID- 29050885
TI  - Does attentional dysfunction and thalamic atrophy predict decline in dementia
      with Lewy bodies?
AB  - INTRODUCTION: To evaluate the clinical characteristics of DLB subjects who died
      within 1 year of assessment compared to those who survived and investigate their
      patterns of in vivo regional thalamic atrophy using structural MRI. METHODS:
      Seventy subjects (35 DLB, 35 aged controls) underwent 3 T T1-weighted MR scanning
      as well as clinical and cognitive assessments, including a computerised
      assessment of attention. All subjects were contacted after 12 months for
      reassessment. For both hemispheres, using FSL FIRST, the thalamus was
      automatically segmented followed by inter-subject vertex-wise analyses involving
      group comparisons and behavioural correlates. RESULTS: There was significant
      bilateral atrophy in the ventral-dorsal and pulvinar regions in DLB relative to
      controls (pcorrected < 0.05). The DLB group was then re-categorised based on 12
      month mortality data: DLB-a (n = 26) and DLB-d (n = 9) (a = alive, d = death
      within 12 months of study assessment). Compared to controls, significant
      attentional dysfunction and bilateral atrophy of the pulvinar, ventral and dorsal
      nuclei were observed in DLB-d (pcorrected < 0.05), whereas in DLB-a, atrophy was
      far less extensive. CONCLUSIONS: Distinct patterns of thalamic atrophy occur in
      DLB that may relate to the attentional dysfunction and cognitive fluctuations
      that characterise this disorder. Relative to controls, the extent of attentional
      impairment and pattern of thalamic degeneration differ in those patients who died
      within 12 months of assessment, despite having an otherwise similar level of
      dementia severity. These findings may provide insight into the neurobiological
      changes underpinning important clinical characteristics and disease
      heterogeneity.

PMID- 29050886
TI  - Disparities in access to emergency general surgery care in the United States.
AB  - BACKGROUND: As fewer surgeons take emergency general surgery call and hospitals
      decrease emergency services, a crisis in access looms in the United States. We
      examined national emergency general surgery capacity and county-level
      determinants of access to emergency general surgery care with special attention
      to disparities. METHODS: To identify potential emergency general surgery
      hospitals, we queried the database of the American Hospital Association for
      "acute care general hospital," with "surgical services," and "emergency
      department," and >=1 "operating room." Internet search and direct contact
      confirmed emergency general surgery services that covered the emergency room 7
      days a week, 24 hours a day. Geographic and population-level emergency general
      surgery access was derived from Geographic Information Systems and US Census.
      RESULTS: Of the 6,356 hospitals in the 2013 American Hospital Association
      database, only 2,811 were emergency general surgery hospitals. Counties with
      greater percentages of black, Hispanic, uninsured, and low-education individuals
      and rural counties disproportionately lacked access to emergency general surgery
      care. For example, counties above the 75th percentile of African American
      population (10.2%) had >80% odds of not having an emergency general surgery
      hospital compared with counties below the 25th percentile of African American
      population (0.6%). CONCLUSION: Gaps in access to emergency general surgery
      services exist across the United States, disproportionately affecting
      underserved, rural communities. Policy initiatives need to increase emergency
      general surgery capacity nationwide.

PMID- 29050888
TI  - Influence of discharge timing and diagnosis on outcomes of pediatric laparoscopic
      cholecystectomy.
AB  - BACKGROUND: This study evaluated the influence of discharge timing (same day
      versus other) on 30-day hospital readmissions after laparoscopic cholecystectomy
      in pediatric patients. Wound complication and readmission rates also were
      evaluated among patients with different operative indications. METHODS: The
      database of the National Surgical Quality Improvement Program-Pediatric (2012
      2015) was queried for patients <18 years old who underwent laparoscopic
      cholecystectomy. Patient and operative variables as well as timing of discharge
      were assessed. Same-day discharge was defined as zero days between operation and
      discharge and was compared with patients discharged on the first or second
      postoperative day. Primary outcome was hospital readmission within 30 days;
      secondary outcomes included surgical site infections and wound complications.
      RESULTS: From 2012-2015, 5,046 patients underwent cholecystectomy (75.0% female;
      median age 13.7 years). Postoperative diagnoses included cholelithiasis (69.6%),
      cholecystitis (16.3%), biliary dyskinesia (12.3%), and pancreatitis (1.8%); all
      other diagnoses were excluded from analysis. Same-day discharge occurred in 1,061
      patients (21.0%). Overall rate of readmission was 3.6% (3.9% among patients
      discharged on postoperative day 1 or 2 and 2.1% for patients discharged on the
      same day as the operation, P = .003). When compared according American Society of
      Anesthesiologists classification, patients of class 3 and class 4 were associated
      with increased odds of 30-day hospital readmission when compared with class 1
      (odds ratio 2.27, 95% confidence interval 1.32-3.89, P = .003 and odds ratio
      7.62, 95% confidence interval 1.47-39.70, P = .02, respectively). Similarly,
      patients with hematologic comorbidities compared with those without comorbidities
      also had increased odds of 30-day readmission (odds ratio 1.88, 95% confidence
      interval, 1.19-2.96, P = .007). Same-day discharge was not associated with
      increased readmission (odds ratio 0.60, 95% confidence interval, 0.38-0.94, P =
      .03) when compared with later discharge. Reasons for readmission did not differ
      between the same-day and later discharge groups. None of the demographic or
      clinical characteristics, including discharge timing, indication or operation,
      and preoperative duration of stay, were associated with increased odds of wound
      complications. CONCLUSION: In pediatric patients undergoing laparoscopic
      cholecystectomy, same-day discharge is not associated with increased 30-day
      hospital readmission rates or wound complications when compared to discharge in 1
      or 2 days. Same-day discharge seems safe and may be an applicable quality
      indicator for pediatric patients undergoing laparoscopic cholecystectomy.

PMID- 29050887
TI  - Antibiotic stewardship in the newborn surgical patient: A quality improvement
      project in the neonatal intensive care unit.
AB  - BACKGROUND: There is significant diversity in the utilization of antibiotics for
      neonates undergoing surgical procedures. Our institution standardized antibiotic
      administration for surgical neonates, in which no empiric antibiotics were given
      to infants with surgical conditions postnatally, and antibiotics are given no
      more than 72 hours perioperatively. METHODS: We compared the time periods before
      and after implementation of antibiotic protocol in an institution review board
      approved, retrospective review of neonates with congenital surgical conditions
      who underwent surgical correction within 30 days after birth. Surgical site
      infection at 30 days was the primary outcome, and development of hospital
      acquired infections or multidrug-resistant organism were secondary outcomes.
      RESULTS: One hundred forty-eight infants underwent surgical procedures pre
      protocol, and 127 underwent procedures post-protocol implementation. Surgical
      site infection rates were similar pre- and post-protocol, 14% and 9%
      respectively, (P = .21.) The incidence of hospital-acquired infections (13.7% vs
      8.7%, P = .205) and multidrug-resistant organism (4.7% vs 1.6%, P = .143) was
      similar between the 2 periods. CONCLUSION: Elimination of empiric postnatal
      antibiotics did not statistically change rates of surgical site infection,
      hospital-acquired infections, or multidrug-resistant organisms. Limiting the
      duration of perioperative antibiotic prophylaxis to no more than 72 hours after
      surgery did not increase the rate of surgical site infection, hospital-acquired
      infections, or multidrug-resistant organism. Median antibiotic days were
      decreased with antibiotic standardization for surgical neonates.

PMID- 29050889
TI  - Nine-point plan to improve care of the injured patient: A case study from Kenya.
AB  - BACKGROUND: Injury rates in low- and middle-income countries are among the
      greatest in the world, with >90% of unintentional injury occurring in low- or
      middle-income countries. The risk of death from injuries is 6 times more in low-
      and middle-income countries than in high-income countries. This increased rate of
      injury is partly due to the lack of availability and access to timely and
      appropriate medical care for injured individuals. Kenya, like most low- and
      middle-income countries, has seen a 5-fold increase in injury fatalities
      throughout the past 4 decades, in large part related to the absence of a
      coordinated, integrated system of trauma care. METHODS: We aimed to assess the
      trauma-care system in Kenya and to develop and implement a plan to improve it. A
      trauma system profile was performed to understand the landscape for the care of
      the injured patient in Kenya. This process helped identify key gaps in care
      ranging from prehospital to hospital-based care. RESULTS: In response to this
      observation, a 9-point plan to improve trauma care in Kenya was developed and
      implemented in close collaboration with local stakeholders. The 9-point plan was
      centered on engagement of the stakeholders, generation of key data to guide and
      improve services, capacity development for prehospital and hospital care, and
      strengthening policy and legislation. CONCLUSION: There is an urgent need for
      coordinated strategies to provide appropriate and timely medical care to injured
      individuals in low- or middle-income countries to decrease the burden of injuries
      and related fatalities. Our work in Kenya shows that such an integrated system of
      trauma care could be achieved through a step-by-step integrated and multifaceted
      approach that emphasizes engagement of local stakeholders and evidence-based
      approaches to ensure effectiveness, efficiency, and sustainability of system-wide
      improvements. This plan and lessons learned in its development and implementation
      could be adaptable to other similar settings to improve the care of the injured
      patient in low- or middle-income countries.

PMID- 29050890
TI  - A case of conus medullaris teratoma.
AB  - In this report, we present a case of an adult patient with a mature teratoma of
      the conus medullaris. The patient was a 29-year-old postpartum female patient who
      developed unexplained urinary retention. Lumbar spine magnetic resonance imaging
      (MRI) examination revealed an intradural partly enhancing mixed cystic and solid
      lesion with intralesional intrinsic T1 hyperintense components that were
      suppressed on fat suppressed sequences, inseparable from the conus medullaris.
      Surgical resection was performed and histopathology findings were consistent with
      a mature teratoma. The patient made a complete recovery.

PMID- 29050891
TI  - Is stand alone PEEK cage the gold standard in multilevel anterior cervical
      discectomy and fusion (ACDF)? Results of a minimum 1-year follow up.
AB  - INTRODUCTION: This study was designed to evaluate the clinical and radiologic
      results of stand-alone synthetic polyetheretherketone (PEEK) cages for two- or
      three-level anterior cervical discectomy and fusion (ACDF), with a focus on
      subsidence. MATERIALS AND METHODS: We retrospectively reviewed a total of 68
      patients who underwent two- or three-level ACDF with a stand-alone PEEK cage
      between April 2005 and August 2016. Radiologic parameters were assessed on
      lateral radiographs, and fusion was assessed on computed tomography scans. For
      the evaluation of clinical outcomes, visual analogue scale, neck disability
      index, and modified Japanese Orthopedic Association scores were measured.
      RESULTS: Among the total of 68 patients with a total of 144 segments, ACDF at two
      and three levels was performed in 60 and 8 patients, respectively, with a mean
      follow-up duration of 27.6 months. The overall fusion rate was 81.3% (117 of 144
      segments), and subsidence occurred in 63 segments (43.8%) at the last follow-up.
      There was no statistically significant difference between the subsidence group
      and the nonsubsidence group in terms of fusion rate, radiologic outcomes, and
      clinical outcomes (p > .05). CONCLUSION: Subsidence might be an inevitable course
      and only a radiologic phenomenon with no effect on the clinical and radiologic
      outcomes of the use of stand-alone cages.

PMID- 29050892
TI  - Traumatic vertebral artery dissection in high school rugby players: A report of
      two cases.
AB  - Traumatic vertebral artery dissection (VAD) has been reported in various types of
      sports and recreation. However, there have been no reports of VAD in rugby
      players, except for those with cervical spine injuries. We experienced two cases
      of VAD without cervical spine injuries in high school rugby players. Attention
      should be paid to protect youth rugby players from VAD.

PMID- 29050893
TI  - Recurrence of chest wall hydatid cyst disease involving the thoracic spine in an
      Australian patient.

PMID- 29050894
TI  - Long-term effect of repetitive transcranial magnetic stimulation on disability in
      patients with stroke.
AB  - High-frequency repetitive transcranial magnetic stimulation (rTMS) is widely used
      to improve motor function in stroke patients. However, the long-term effects of
      rTMS on disability and motor function are not clear. We investigated the effects
      of high-frequency rTMS administered within 1 month of stroke on disability and
      motor function 6 months after stroke onset. The study was conducted by an open
      label longitudinal study, and were included 76 (38 rTMS and 38 control) subacute
      stroke patients. The rTMS group received 10 Hz stimulation over the primary motor
      cortex of the affected hemisphere for 10 days with a daily dose of 1000 pulses.
      The Korean version of the Modified Barthel Index (K-MBI), the Medical Research
      Council (MRC) scale for motor deficits in the affected arm, the Manual Function
      Test (MFT), and the Functional Ambulation Classification (FAC) were administered
      at baseline (within 1 month of stroke onset) and at 3 and 6 months after onset.
      The K-MBI, MRC scale, MFT, and FAC scores of both groups changed significantly
      over time (p < 0.001); however, the motor strength, hand function, FAC
      classification, and K-MBI scores of the rTMS and control groups did not differ.
      Our findings indicate that rTMS did not have a long-lasting effect (6 months
      after onset) on disability and motor function in patients with stroke.

PMID- 29050895
TI  - Minimal invasive lumbar spine revision surgery at distance from the dura and
      postsurgical scar tissue: Extraforaminal Lumbar Interbody Fusion (ELIF).
AB  - Lumbar spine revision surgery is considered as challenging and related to longer
      operation time and complications because of the loss of anatomical landmarks and
      the formation of postoperative epidural fibrosis. Minimal invasive lumbar spinal
      surgery techniques have been refined over the last 5 years but the reexposure of
      the dura, the formation of postsurgical scar tissue and related dural tears
      remain a source of complications. For lumbar spinal revision surgery we advocate
      the minimal invasive Extraforaminal Lumbar Interbody Fusion (ELIF) technique. It
      employs a working corridor of 45 degrees  relative to the midline. This angle
      permits bypassing laterally the dural sac and postoperative epidural fibrosis so
      that dural tears do not occur. ELIF is performed without an expandable tubular
      retractor system, it is atraumatic following the natural intermuscular cleavage
      plane between the multifidus muscle and the longissimus thoracis muscle pars
      lumborum. Postoperatively the muscles do not show signs atrophy or fatty
      degeneration. In case of discectomy alone there is no need for the removal of the
      facets, if intracanalar lesions are targeted the partial removal of the superior
      facet is sufficient. ELIF represents an alternative to posterior lumbar interbody
      fusion (PLIF), conventional open transforaminal lumbar interbody fusion (TLIF),
      and minimal invasive (MIS) TLIF for lumbar spinal revision surgery.

PMID- 29050896
TI  - Intraoperative pedicle screw navigation does not significantly affect
      complication rates after spine surgery.
AB  - Various forms of intraoperative computer-assisted navigation technologies exist,
      and have consistently been shown to improve pedicle screw accuracy. However, the
      overall clinical effects of inaccurate pedicle screw placement have been debated.
      We examined the clinical effects of improved pedicle screw accuracy with computer
      navigation technology in reducing complication rates in patients undergoing multi
      level spinal fusion. We retrospectively reviewed the ACS-NSQIP registry utilizing
      Current Procedural Terminology (CPT) codes 22843 + 22844 to identify patients
      undergoing spinal instrumentation of greater than 7 levels, as well as the CPT
      code 61783 to denote the use of intraoperative computer-assisted navigation. The
      data were then subdivided to into cohorts consisting of instrumentation cases
      with and without navigation. Demographic information, as well as intraoperative
      and postoperative complications, were compared between groups. A total of 3168
      patients met our inclusion criteria. There were no statistically significant
      differences in preoperative population data. Surgical time was significantly
      longer in the navigation group (391.41 versus 350.3 min), but there were no
      significant improvements in complication rates with the use of navigation. We
      found that the mean operative time was significantly increased for patients
      undergoing spinal instrumentation with computer navigation. This increase in
      operative time was not associated with any increase in surgical or medical
      complications. However, in this large series, we were unable to show any clinical
      benefit to intraoperative navigation, and no reductions in short term
      complications or rates of return to surgery were observed.

PMID- 29050897
TI  - A retrospective study of bevacizumab for treatment of brainstem glioma with
      malignant features.
AB  - Brainstem glioma is impossible to resect completely, and patients with this type
      of glioma show a poor prognosis. Therefore, a more effective adjuvant therapy is
      required to prolong survival. Bevacizumab is an endothelial growth factor
      monoclonal antibody with strong anti-vascular effects, which may suppress tumor
      progression. We performed a retrospective study of data from 6 patients with
      brainstem glioma showing malignant features who were treated with bevacizumab.
      Tumor-associated lesions, as evaluated by T2 weighted or fluid-attenuated
      inversion-recovery magnetic resonance imaging, were reduced in all patients,
      although the timing of the start of bevacizumab administration and pretreatment
      were not uniform. Clinical symptoms improved in 4 patients and progression was
      inhibited in 2 patients. The Karnofsky performance status improved from 56.7 to
      71.7 on average. The median reduction ratio of tumor-associated lesions was
      76.3%, but tumor suppression did not last in any of the cases. Furthermore, 5
      patients died of tumor progression, and 1 patient died of a complication of
      necrotizing colitis. The median progression-free survival after bevacizumab
      administration was 7 months. The median overall survival after diagnosis was 16.5
      months. Bevacizumab might be a potential therapeutic option for progressive
      brainstem gliomas with malignant features.

PMID- 29050898
TI  - Sushi, ceviche and gnathostomiasis - A case report and review of imported
      infections.
AB  - We describe a case of imported cutaneous gnathostomiasis in a Thai patient living
      in France. Gnathostomiasis is a zoonosis of food origin. The disease is endemic
      in Southeast Asia and Latin America. However, over the past 30 years, an
      increasing number of imported cases has been described in Europe and America. The
      disease is rare in Western Europe and the majority of cases described had a
      cutaneous clinical presentation. The disease may sometimes be confused with
      allergy, leading to a delay in diagnosis. Visceral symptoms are rare but may
      follow severe attacks. A definitive diagnosis can be obtained by the isolation of
      larvae from skin biopsies, but these are rarely performed. The diagnosis is
      usually presumptive, based on a combination of anamnestic, clinical, and
      biological factors. Several courses of the anti-helminths, albendazole or
      ivermectin, are often necessary. Although rare, the diagnosis should be evoked
      systematically in a migrant or traveller returning from an endemic area with
      cutaneous lesions.

PMID- 29050900
TI  - Bone and mineral disorders in chronic kidney disease: implications for
      cardiovascular health and ageing in the general population.
AB  - The patient with chronic kidney disease (CKD) represents an extreme model for
      arteriosclerosis, vascular calcification, and bone disorders, all of which are
      also associated with ageing in the general population. These pathological
      features are also relevant to other common chronic health disorders such as
      diabetes, and chronic inflammatory and cardiovascular diseases. Although
      management and interventions for these major risk factors are now incorporated
      into most public health guidelines (eg, smoking cessation and control of
      bodyweight and blood pressure, as well as glucose and cholesterol
      concentrations), some residual cardiovascular risk is not reduced by
      implementation of these interventions. CKD should be regarded as an atypical
      disease in which both traditional and novel cardiovascular risk factors have
      effects on outcomes. But CKD can also be viewed conceptually as an accelerator of
      traditional cardiovascular risk factors. Findings from research into mineral bone
      disorder associated with CKD (CKD-MBD) could help the medical community to better
      understand the vascular actions of certain molecules, such as phosphates,
      fibroblast growth factor 23, parathyroid hormone, sclerostin, or vitamin D and
      their relevance to the management of different pathologies in the general
      population. Importantly, these components, which are recognised in nephrology,
      could help to explain residual risk of cardiovascular events in the general
      population. Thus, achieving a better understanding of CKD-MBDs could provide
      substantial insight into future treatments for arteriosclerosis and osteoporosis,
      which are strongly associated with ageing and morbidity in the general
      population.

PMID- 29050899
TI  - Acute Rupture of the Left Common Iliac Artery After Sigmoid Diverticulitis.

PMID- 29050901
TI  - Medical device-related pressure injuries: An exploratory descriptive study in an
      acute tertiary hospital in Australia.
AB  - AIM: To examine and explore medical device-related pressure injuries in an 800
      bed tertiary hospital. MATERIALS AND METHODS: An exploratory descriptive study
      design was employed. A prospective review of all data on reported hospital
      acquired pressure injuries was conducted on a weekly basis from July 2015 to
      August 2016. This included a patient assessment and medical record review as well
      as brief semi-structured interviews with nurses. RESULTS: The overall incidence
      of medical device-related pressure injuries was 27.9% (50/179) with the majority
      (68%, 34/50) occurring in intensive care. The most common cause of a medical
      device-related pressure injury was oxygen tubing behind ears (n = 21) and
      endotracheal tubes (n = 13). Nurses were unaware of the implications of medical
      devices in contact with the skin and patient medical records did not present a
      valuable source of information in relation to pressure injury prevention.
      CONCLUSION: Medical device-related pressure injuries were represented in 27.9% of
      our entire patient cohort; primarily occurring on the ear from oxygen tubing and
      on the mouth from endotracheal tubes in patients in intensive care. Additional
      support, education and monitoring for nurses at a local level on the prevention
      of medical device-related pressure injuries is necessary to prevent their
      occurrence. Furthermore, consensus on the classification and reporting of medical
      device-related pressure injuries is still in development, making reporting and
      monitoring challenging. Medical device-related pressure injuries are a continuing
      clinical issue that require further exploration.

PMID- 29050903
TI  - Hospital Acquired Pneumonia Prevention Initiative-2: Incidence of nonventilator
      hospital-acquired pneumonia in the United States.
AB  - BACKGROUND: Because nonventilator hospital-acquired pneumonia (NV-HAP) is
      understudied, our purpose was to determine the incidence, overall burden, and
      level of documented pneumonia preventive interventions of NV-HAP in 24 U.S.
      hospitals. METHODS: This retrospective chart review extracted NV-HAP cases as per
      the 2014 ICD-9-CM codes for pneumonia not present on admission and the 2013
      Centers for Disease Control and Prevention case definition. Patient demographic
      data, outcomes, and documented preventive interventions were also collected.
      RESULTS: We found 1,300 NV-HAP patients who acquired NV-HAP (rate, 0.12-2.28 per
      1,000 patient days) across the 21 hospitals that completed the data collection.
      Most NV-HAP infections (70.8%) were acquired outside of intensive care units
      (ICUs); 18.8% required transfer into the ICU. In the 24 hours prior to diagnosis,
      most of the patients did not have fundamental hospital care associated with
      pneumonia prevention. CONCLUSIONS: This multicenter, nationwide study highlights
      the significant burden of NV-HAP in the U.S. acute care hospital setting. We
      found that NV-HAP occurred on every hospital unit, including in younger, healthy
      patients. This indicates that although some patients are clearly at higher risk,
      all patients carry some NV-HAP risk. Therapeutic interventions aimed at NV-HAP
      prevention are frequently not provided for patients in acute care hospitals.

PMID- 29050904
TI  - The heroic microbe.

PMID- 29050902
TI  - Housing conditions modulate the reinforcing properties of cocaine in adolescent
      mice that binge on fat.
AB  - Binge eating is a specific form of overeating characterized by intermittent,
      excessive eating. To date, several studies have addressed the effects that
      bingeing on fat has on the rewarding effects of drugs of abuse, but they have
      found contradictory and highly variable results. Housing conditions could
      modulate these results, as most studies employ isolated animals to measure the
      exact amount of food that is ingested. The aim of this study was to evaluate the
      effects of housing conditions on the response of mice to cocaine, modulated by
      bingeing on a high-fat diet during adolescence. After 40days of binge-eating for
      2h, three days a week (PND 29-69), the reinforcing effects of a non-effective
      dose of cocaine (1mg/kg) was evaluated using the conditioned place preference
      (CPP) paradigm. The anxiolytic profile using the Elevated Plus Maze and
      circulating leptin and corticosterone levels were also assessed. Our results show
      a significant escalation in the consumption of a high-fat diet between the first
      and the last week in both types of housed mice. Among the grouped mice, only
      those exposed to high-fat binge (HFB) developed CPP. Conversely, isolated mice
      fed with standard diet were more sensitive to the rewarding effects of a
      subthreshold dose of cocaine than those fed with HFB. Plasma leptin levels were
      elevated in both groups that developed CPP. Although isolated animals presented
      higher corticosterone levels with respect to the grouped ones, anxiety levels did
      not differ. Therefore, our results highlight the importance of housing conditions
      on the effects that a high-fat diet exerts on cocaine reward.

PMID- 29050905
TI  - The epidemiology of nonventilator hospital-acquired pneumonia in the United
      States.
AB  - BACKGROUND: Nonventilator hospital-acquired pneumonia (NV-HAP) is among the most
      common hospital-acquired infections. The purpose of our study was to quantify the
      incidence and influence of NV-HAP in the United States using a national dataset.
      METHODS: The 2012 US National Inpatient Sample dataset was used to compare an NV
      HAP group to 4 additional group cohorts: pneumonia on admission, general hospital
      admissions, matched on mortality and disease severity, and ventilator-associated
      pneumonia (VAP). The main outcome was NV-HAP incidence. The secondary outcome was
      to compare hospital length of stay, total hospital charges, and mortality between
      the NV-HAP group and the 4 additional group cohorts. RESULTS: The overall
      incidence of NV-HAP was 1.6%, which represents a rate of 3.63 per 1,000 patient
      days. NV-HAP was associated with increased total hospital charges, a longer
      hospital length of stay, and greater likelihood of death in comparison to all
      groups except patients with VAP. CONCLUSION: NV-HAP is an underappreciated and
      serious patient safety issue, resulting in significant increases in cost, length
      of stay, and mortality. Efforts toward prevention of NV-HAP should be raised to
      the same level of concern as VAP prevention.

PMID- 29050906
TI  - Hospital readmissions related to Clostridium difficile infection in the United
      States.
AB  - Using a national readmissions database, we report a significant burden of
      Clostridium difficile-associated readmissions in the United States manifested as
      a high rate of rehospitalizations and substantial hospital stays and costs.

PMID- 29050907
TI  - Difficulties in using personal protective equipment: Training experiences with
      the 2015 outbreak of Middle East respiratory syndrome in Korea.
AB  - This study aimed to evaluate practical barriers to personal protective equipment
      (PPE) use found through health care personnel (HCP) training sessions held during
      and after the 2015 Middle East respiratory syndrome outbreak in Korea.
      Difficulties observed were ill-fitting sizes, anxiety, confusion from
      unstandardized protocols, doubts about PPE quality and effectiveness, and
      complexity of using several PPE items together. Further research to generate
      robust evidence and repeated HCP trainings are necessary to ensure HCP and
      patient safety in future outbreaks.

PMID- 29050908
TI  - Hand hygiene: Attitudes and practices of nurses, a comparison between 2007 and
      2015.
AB  - BACKGROUND: Hand hygiene reduces health care-associated infections significantly.
      However, international evidence suggests that practices are suboptimal. The
      objective of this study was to compare and contrast hand hygiene attitudes and
      practices and alcohol-based handrub (ABHR) use among nurses between 2007 and
      2015. METHODS: In 2007, a random sample of nurses in a large teaching hospital
      was invited to complete a postal survey using a validated questionnaire. In 2015,
      the study was replicated among all nurses employed in a university hospital
      group, including the setting of the original study. Data were analyzed
      quantitatively and qualitatively using appropriate software. RESULTS: Attitudes
      to hand hygiene were positive and >90% of respondents' self-reported compliance
      before and after patient contact. However, 13% fewer in 2015 (42%) reported using
      ABHR >90% of the time compared with in 2007 (55%). Of nurses with <2 years'
      experience, 90% reported using ABHR >50% of the time compared with 73% of nurses
      with 2-5 years' experience. Barriers to ABHR improved, but remained high (skin
      sensitivity: 2007: 23%, 2015: 17%; skin damage: 2007: 18%, 2015: 13%; poor user
      acceptability and tolerance: 2007 and 2015: 25%). CONCLUSIONS: Use of positive
      role models, the adoption of a positive social and cultural norm within the
      organization, and the provision of continuing professional development
      opportunities may prove useful strategies in harnessing good practice among
      graduate nurses and in preventing negative socialization from occurring.

PMID- 29050909
TI  - BOLD-fMRI in the mouse auditory pathway.
AB  - The auditory pathway is widely distributed throughout the brain, and is perhaps
      one of the most interesting networks in the context of neuroplasticity. Accurate
      mapping of neural activity in the entire pathway, preferably noninvasively, and
      with high resolution, could be instrumental for understanding such longitudinal
      processes. Functional magnetic resonance imaging (fMRI) has clear advantages for
      such characterizations, as it is noninvasive, provides relatively high spatial
      resolution and lends itself for repetitive studies, albeit relying on an indirect
      neurovascular coupling to deliver its information. Indeed, fMRI has been
      previously used to characterize the auditory pathway in humans and in rats. In
      the mouse, however, the auditory pathway has insofar only been mapped using
      manganese-enhanced MRI. Here, we describe a novel setup specifically designed for
      high-resolution mapping of the mouse auditory pathway using high-field fMRI.
      Robust and consistent Blood-Oxygenation-Level-Dependent (BOLD) responses were
      documented along nearly the entire auditory pathway, from the cochlear nucleus
      (CN), through the superior olivary complex (SOC), nuclei of the lateral lemniscus
      (LL), inferior colliculus (IC) and the medial geniculate body (MGB). By contrast,
      clear BOLD responses were not observed in auditory cortex (AC) in this study.
      Diverse BOLD latencies were mapped ROI- and pixel-wise using coherence analysis,
      evidencing different averaged BOLD time courses in different auditory centers.
      Some degree of tonotopy was identified in the IC, SOC, and MGB in the pooled
      dataset though it could not be assessed per subject due to a lack of statistical
      power. Given the importance of the mouse model in plasticity studies, animal
      models, and optogenetics, and fMRI's potential to map dynamic responses to
      specific cues, this first fMRI study of the mouse auditory pathway paves the way
      for future longitudinal studies studying brain-wide auditory-related activity in
      vivo.

PMID- 29050910
TI  - Default mode network connectivity of fear- and anxiety-related cue and context
      conditioning.
AB  - Classical fear conditioning is an important mechanism to adequately respond and
      adapt to environmental threats and has been related to the development of fear
      and anxiety. Both cue and context conditioning have been studied but little is
      known about their relation to relevant resting state networks. The default mode
      network (DMN) has been reported to be involved in affective learning and
      described as facilitating a state of readiness in responding to environmental
      changes. We examined resting state brain connectivity patterns of the default
      mode network (DMN) in 119 healthy volunteers. Specifically, we carried out
      correlation analyses between the DMN and skin conductance responses (SCRs) as
      well as arousal, valence and contingency ratings during learning. In addition, we
      examined the role of trait anxiety. Two different DMN patterns were identified in
      which stronger connectivity was linked to lower differential SCRs during fear and
      anxiety learning. One was related to cue conditioning and involved the amygdala
      and the medial prefrontal cortex, and one was associated with context
      conditioning and included the hippocampal formation and sensorimotor areas. These
      results were replicated in an independent sample. Functional connectivity of the
      DMN with these key regions at rest was also predictive of trait anxiety but this
      association could not be replicated in the second sample. We showed that DMN
      connectivity is differently associated with cued versus contextual learning
      mechanisms. Uncovering individual differences in baseline network connectivity of
      the DMN with these key regions might lead to a better understanding of fear and
      anxiety. Such findings could indeed help to identify vulnerability factors linked
      to network alterations at rest with dysregulation of learning processes involved
      in the pathophysiology of stress and anxiety disorders.

PMID- 29050911
TI  - The Multi-Faceted Relationship between White Matter Lesions and Late-Life
      Depression.

PMID- 29050912
TI  - A Systematic Review of the Measurement of Function in Late-Life Depression.
AB  - Recovery of everyday premorbid function is a primary goal in the treatment of
      depression. Measurement of function is an important part of achieving this goal.
      A multitude of scales have been used to measure function in depression,
      reflecting the complex, multifaceted nature of functioning. Currently, however,
      there are no evidence-based guidelines to assist the researcher or clinician in
      deciding which instruments are best suited to measure function in late-life
      depression (LLD). Thus, the aims of this study are to 1) systematically review
      and identify the instrumental activities of daily living and social functioning
      assessment instruments used in the LLD literature; 2) identify and appraise the
      measurement properties of these instruments; and 3) suggest factors for LLD
      researchers and clinicians to consider when selecting functional assessment
      instruments and make pertinent recommendations. We performed a systematic review
      of MEDLINE and CINAHL to identify studies that i) incorporated subjects aged 60
      years and older with a depressive disorder, and ii) measured instrumental
      activities of daily living and/or social functioning. Our search yielded 21
      functional assessment instruments. Only two of these instruments, the 36-Item
      Short Form Survey and the Performance Assessment of Self-Care Skills, have formal
      validation data in LLD. Four additional instruments, although not formally
      validated, have relevant data regarding their measurement properties. The primary
      finding of this study is that very few functional assessment instruments have
      been validated in LLD, and the available measurement property data are mixed;
      there is a need for further instrument validation in late-life depression. With
      this caveat in mind, we provide evidence-based suggestions for researchers and
      clinicians assessing functioning in LLD patients.

PMID- 29050914
TI  - Two Sides of Bipolar Disorder in Nursing Homes: Mental Healthcare and Quality
      Indicators.

PMID- 29050913
TI  - Blood Pressure's Role in Alzheimer Disease Pathology.

PMID- 29050915
TI  - Decellularized matrix of adipose-derived mesenchymal stromal cells enhanced
      retinal progenitor cell proliferation via the Akt/Erk pathway and neuronal
      differentiation.
AB  - BACKGROUND AIMS: Retinal progenitor cells (RPCs) are a promising cell therapy
      treatment for retinal degenerative diseases. However, problems with limited
      proliferation ability and differentiation preference toward glia rather than
      neurons restrict the clinical application of these RPCs. The extracellular matrix
      (ECM) has been recognized to provide an appropriate microenvironment to support
      stem cell adhesion and direct cell behaviors, such as self-renewal and
      differentiation. METHODS: In this study, decellularized matrix of adipose-derived
      mesenchymal stromal cells (DMA) was manufactured using a chemical agent method
      (0.5% ammonium hydroxide Triton + 20 mmol/L NH4OH) in combination with a
      biological agent method (DNase solution), and the resulting DMA were evaluated by
      scanning electron microscopy (SEM) and immunocytochemistry. The effect of DMA on
      RPC proliferation and differentiation was evaluated by quantitative polymerase
      chain reaction, Western blot and immunocytochemistry analysis. RESULTS: DMA was
      successfully fabricated, as demonstrated by SEM and immunocytochemistry. Compared
      with tissue culture plates, DMA may effectively enhance the proliferation of RPCs
      by activating Akt and Erk phosphorylation; when the two pathways were blocked,
      the promoting effect was reversed. Moreover, DMA promoted the differentiation of
      RPCs toward retinal neurons, especially rhodopsin- and recoverin-positive
      photoreceptors, which is the most interesting class of cells for retinal
      degeneration treatment. CONCLUSIONS: These results indicate that DMA has
      important roles in governing RPC proliferation and differentiation and may
      contribute to the application of RPCs in treating retinal degenerative diseases.

PMID- 29050916
TI  - Platelet rich plasma and growth factors cocktails for diabetic foot ulcers
      treatment: State of art developments and future prospects.
AB  - Current advances in diabetic foot ulcers (DFU) treatment are discussed. Normal
      and pathological wound healing process are observed and the role of growth
      factors (GFs) is elucidated. Current techniques involving GFs and platelet rich
      plasma (PRP) are compared. Up-to-date research suggests that treatment with
      single growth factor (GF) could be insufficient and not encompassing all
      pathological changes in DFU bed. Efficiency of PRP is rather controversial and
      lacks evidence. Thus the use of cocktail of particular GFs is suggested. Pro et
      contra of each approach are discussed.

PMID- 29050917
TI  - Sugar intake in Sudanese individuals was associated with some features of the
      metabolic syndrome: Population based study.
AB  - AIM: The aim of this study was to assess the level of sugar intake among Sudanese
      individuals. MATERIALS AND METHODS: A cross-sectional study with 323
      participants. Respondents were grouped by the total intake of added sugars into
      two groups, one group with sugar intake more than 200 calories per day and other
      group with sugar intake less than 200 calories per day. Demographic data were
      collected with anthropometric measurements like body mass index (BMI) and waist
      circumference. Chi square, T-Tests and stepwise logistic regression were used (a
      p-value <0.05 was considered significant). RESULTS: High sugar intake was noted
      among 74.6% participants and among overweight, normal weight, followed by obese
      (p<0.015) and then individuals with diabetes and hypertension (p <0.000 and 0.038
      respectively).High sugar intake was also associated with abdominal obesity
      (p<0.016), mean age of 33 years old (p<0.00) and being married and
      single(p<0.003). Stepwise logistic regression showed diabetes and BMI<25 were
      absolute predictors for sugar consumption with p value of 0.001 and 0.039
      respectively. Individuals with diabetes have more than five times probability to
      consume large amount of sugar (Odd ratio 5.6), while those with BMI<25 have two
      times risk of consuming more sugar compared to those with BMI>25 group (Odd ratio
      2.1). CONCLUSION: A large percentage of Sudanese population uses a high amount of
      sugar. High sugar intake was associated with normal weight, overweight, abdominal
      obesity, diabetes and hypertension. Absolute predictors of high sugar intake were
      diabetes and normal body weight.

PMID- 29050918
TI  - Assessing the Effect of Lifetime Contralateral Breast Cancer Risk on the
      Selection of Contralateral Prophylactic Mastectomy for Unilateral Breast Cancer.
AB  - INTRODUCTION: Contralateral prophylactic mastectomy (CPM) rates are rising, with
      fear implicated as a contributing factor. This study used a contralateral breast
      cancer (CBC) risk stratification tool to assess whether the selection of CPM is
      reflective of future CBC risk. PATIENTS AND METHODS: This retrospective study
      evaluated 404 women with unilateral breast cancer treated with breast
      conservation, unilateral mastectomy, or bilateral mastectomy within a single
      multidisciplinary clinic. Women were evaluated by the Manchester risk tool to
      calculate lifetime CBC risk. Logistic regression analysis was used to evaluate
      whether CBC risk was associated with CPM, and the clinical rationale for
      prophylactic mastectomy justification was recorded. RESULTS: Sixty-two percent
      underwent breast conservation, 18% unilateral mastectomy, and 20% bilateral
      mastectomy. In the CPM cohort, 36% had > 20% calculated lifetime CBC risk. In the
      invasive cohort, younger age (odds ratio 2.65, P < .0001) and genetic mutation
      positivity (odds ratio 35.39, P = .019) independently predicted CPM. Other
      contributing factors included benign contralateral breast findings (29%) and
      recommendations against breast conservation due to disease burden (28%). Six
      percent selected CPM as a result of an unsubstantiated fear regarding breast
      cancer. CONCLUSION: The majority of women (63%) who selected CPM had < 20% CBC
      risk. In these lower-risk women selecting CPM, factors increasing reasonable fear
      dominated surgical choice (81% of this subset).

PMID- 29050919
TI  - Anthelmintic therapy of equine cyathostomin nematodes - larvicidal efficacy, egg
      reappearance period, and drug resistance.
AB  - Cyathostomins are ubiquitous in grazing horses across the world, and anthelmintic
      resistance has been reported with increasing levels over past decades. The aims
      of the present study were (i) to investigate the efficacy against encysted larval
      stages of moxidectin (0.4 mg/kg) and fenbendazole (10 mg/kg daily for five
      consecutive days) and compare these regimens at 2 and 5 weeks post-treatment,
      (ii) to investigate individual cyathostomin species associated with shortened egg
      reappearance periods, and (iii) to document species exhibiting decreased
      susceptibility to the evaluated compounds. Thirty-six ponies were allocated to
      treatment groups with half euthanatized 2 weeks post-treatment, and the remainder
      necropsied after 5 weeks. Luminal and mucosal worm counts were conducted and
      strongyle egg counts were determined at weekly intervals. At 2 weeks, mean
      reductions of early L3s were 50.4% and 73.8% for fenbendazole and moxidectin,
      respectively. At 5 weeks, the respective efficacies were 51.3% and 71.8%. Two
      week efficacies against late L3s and L4s (LL3s/L4s) were 70.8% and 74.6% for
      fenbendazole and moxidectin, respectively, whereas very low numbers were found in
      all three groups at 5 weeks. None of the mucosal counts were significantly
      different between treatment groups. Fenbendazole and moxidectin reduced luminal
      worm counts by 93.2% and 98.3% at 2 weeks following administration, with
      moxidectin group adult counts being significantly lower than the other two groups
      (P < 0.0001). Both treatment groups had increased counts 3 weeks later (P =
      0.0415). A moxidectin ERP of 4 weeks was associated with surviving luminal L4s,
      and adult species contributing to this were Cyathostomum catinatum,
      Cylicostephanus longibursatus, Cylicocyclus ashworthi and Cylicocyclus nassatus.
      This study documented (i) larvicidal efficacy of fenbendazole much lower than
      historical standards, (ii) survival of luminal immatures (L4) following
      moxidectin administration, and (iii) new information about cyathostomin species
      associated with these phenomena.

PMID- 29050921
TI  - The phenomena of mechanical interaction of segments of hypertrophied myocardium.
AB  - The main aims of adaptation mechanisms of heart contractility are to regulate the
      stroke volume and optimize the global heart function. These mechanisms manifest
      themselves in hearts of healthy animals and in hearts with severe hypertrophy in
      different ways. Severe right ventricle hypertrophy was induced by single
      treatment with monocrotaline. Young rats of both sexes were used to prevent
      influences of sex hormones on the development of right ventricular hypertrophy.
      Serial duplex method is used as a model of interaction of two ventricular wall
      segments. In serial duplex the muscles are in connection 'end-to-end' and
      subjected to mutual deformations during contractions. It is important to
      establish the fine-tuning phenomena and evaluate their expressiveness in healthy
      hearts and hearts with severe hypertrophy. Mild force transient processes occur
      on muscle connection to serial duplex and on muscle separation from duplex in all
      experimental groups. These transients manifest themselves as slow changes in the
      amplitude of muscle contraction from cycle to cycle. During the muscle
      interaction in the serial duplex, evident transient processes in the mutual
      amplitude of deformations in all experimental groups are observed. The greatest
      changes in the length occur in the relaxation phase of the contraction cycle. The
      loss of interaction between ventricular muscles of rats with severe heart
      hypertrophy is the most likely cause of an additional deterioration in the heart
      pumping function. New targets may occur for the recovery of contractility of
      hearts with severe hypertrophy.

PMID- 29050920
TI  - Critique of pure free energy principle: Comment on "Answering Schrodinger's
      question: A free-energy formulation" by Maxwell James Desormeau Ramstead et al.

PMID- 29050922
TI  - The impact of supraventricular ectopic complexes in different age groups and risk
      of recurrent atrial fibrillation after antiarrhythmic medication or catheter
      ablation.
AB  - INTRODUCTION: Supraventricular ectopic complexes (SVEC) are known risk factors of
      recurrent atrial fibrillation (AF). However, the impact of SVEC in different age
      groups is unknown. We aimed to investigate the risk of AF recurrence with higher
      SVEC burden in patients +/-57years, respectively, after treatment with
      antiarrhythmic medication (AAD) or catheter ablation (CA). METHODS: In total, 260
      patients with LVEF >40% and age <=70 years were randomized to AAD (N=132) or CA
      (N=128) as first-line treatment for paroxysmal AF. All patients underwent 7-day
      Holter monitoring at baseline, and after 3, 6, 12, 18 and 24months and were
      categorized according to median age +/-57years. We used multivariate Cox
      regression analyses and we defined high SVEC burden at 3months of follow-up as
      the upper 75th percentile >195SVEC/day. AF recurrence was defined as AF >=1min,
      AF-related cardioversion or hospitalization. RESULTS: Age >57years were
      significantly associated with higher AF recurrence rate after CA (58% vs 36%,
      p=0.02). After CA, we observed a higher SVEC burden during follow-up in patients
      >57years which was not observed in the younger age group treated with CA
      (p=0.006). High SVEC burden at 3months after CA was associated with AF recurrence
      in older patients but not in younger patients (>57years: HR 3.4 [1.4-7.9],
      p=0.005). We did not find any age-related differences after AAD. CONCLUSION: We
      found that younger and older patients respond differently to CA and that SVEC
      burden was only associated with AF recurrence in older patients.

PMID- 29050923
TI  - A systematic review of in-hospital worsening heart failure as an endpoint in
      clinical investigations of therapy for acute heart failure.
AB  - BACKGROUND: In-hospital worsening heart failure (WHF) occurs frequently in
      patients hospitalized for acute heart failure (AHF) and has strongly negative
      prognostic associations. It may be a useful endpoint in studies of AHF management
      but important questions remain regarding optimization of its definition and
      variability in its incidence. METHODS: Our objective was to survey the full
      extent of clinical interest in WHF and assess the impact of baseline variables
      and trial design on outcomes. PubMed, Embase, and BIOSIS were searched
      systematically for clinical studies that had in-hospital WHF as an endpoint.
      Differences in definitions of in-hospital WHF were reviewed for their potential
      impact on observed incidence of WHF and its associations with post-discharge
      outcomes. RESULTS: The search identified 35 publications representing 13
      interventional trials, 3 observational studies, several different classes of
      therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF
      varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way
      in which WHF was defined, two important factors were physician determination of
      worsening and whether intensification of diuretic therapy alone was defined as a
      WHF event. Patients having in-hospital WHF were at substantially greater risk for
      death and longer length of stay during index hospitalizations, all-cause and
      heart-failure rehospitalization, cardiovascular complications, renal failure, all
      cause death, cardiovascular death, and higher healthcare costs post-discharge.
      CONCLUSIONS: There is diverse interest in selecting in-hospital WHF as an
      endpoint in clinical trials. Differences in reported incidence are complexly
      related to differences in the way in which WHF is defined.

PMID- 29050924
TI  - [Progression of nerve fiber layer defects in retrobulbar optic neuritis by the
      macular ganglion cell complex].
AB  - INTRODUCTION: Recent studies with SD OCT had shown early axonal damage to the
      macular ganglion cell complex (which consists of the three innermost layers of
      the retina: Inner Plexiform Layer [IPL], Ganglion Cell Layer [GCL], Retinal Nerve
      Fibre layer [RNFL]) in optic nerve pathology. Retrobulbar optic neuritis (RBON),
      occurring frequently in demyelinating diseases, leads to atrophy of the optic
      nerve fibers at the level of the ganglion cell axons, previously described in the
      literature. The goal of this study is to evaluate the progression of optic nerve
      fiber defects and macular ganglion cell complex defects with the SPECTRALIS OCT
      via a reproducible method by calculating a mean thickness in each quadrant after
      an episode of retrobulbar optic neuritis. METHODS: This is a prospective
      monocentric observational study including 8 patients at the Clermont-Ferrand
      university medical center. All patients underwent ocular examination with macular
      and disc OCT analysis and a Goldmann visual field at the time of inclusion (onset
      or recurrence of RBON), at 3 months and at 6 months. RESULTS: Patients were 40
      years-old on average at the time of inclusion. After 6 months of follow-up, there
      was progression of the atrophy of the macular ganglion cell complex in the
      affected eye on (11.5% or 11MUm) predominantly inferonasally (13.9% or 16MUm) and
      superonasally (12.9% or 14MUm) while the other eye remained stable. The decrease
      in thickness occurred mainly in the most internal 3 layers of the retina. On
      average, the loss in thickness of the peripapillary RNFL was predominantly
      inferotemporal (24.9% or 39MUm) and superotemporal (21.8% or 28MUm). DISCUSSION:
      In 3 months of progression, the loss of optic nerve fibers is already seen on
      macular and disc OCT after an episode of RBON, especially in inferior quadrants
      in spite of the improvement in the Goldmann visual field and visual acuity.
      Segmentation by quadrant was used here to compare the progression of the defect
      by region compared to the fovea in a global and reproducible way. The loss of
      thickness, predominantly inferonasally and superonasally, appears to correspond
      to the temporal loss on optic nerve OCT according to the literature. CONCLUSION:
      The follow-up of these patients with retrobulbar neuritis is important as shown
      by the possibility of relapse, especially in multiple sclerosis. Monitoring of
      the macular ganglion cell complex by a global method of calculation could
      contribute to the detection and localization of early damage after an episode of
      retrobulbar neuritis. This could possibly lead to a discussion of treatment
      modification or increased surveillance in cases of early detection of nerve fiber
      atrophy, or to showing the importance of monitoring, since monitoring of RBON is
      not standardized.

PMID- 29050925
TI  - [Descemetocele].

PMID- 29050927
TI  - [Validation of the French version of the health-related quality of life
      questionnaire for adult strabismus (AS-20)].
AB  - INTRODUCTION: A growing number of articles have shown the negative impact of
      strabismus on self image, relationships with others and professional life. The AS
      20 is a standardized questionnaire in English measuring the psychosocial impact
      of strabismus in adults. The goal of this study is to validate the AS-20 in the
      French language. PARTICIPANTS: Three hundred and ninety one patients took part in
      the study: 131 had strabismus (group 1), 128 other ocular diseases (group 2) and
      132 "normal" patients (group 3). RESULTS: The AS-20 scale showed good
      psychometrical properties in 2 or 4 dimensions: internal consistency was very
      good (Cronbach's alpha coefficient>0.9 in all dimensions and overall) and the
      reproducibility was satisfactory (intra class coefficient>0.7). The comparison of
      the scores in the 2 dimension scale showed significant differences between the
      groups (P<0.001): lower score in strabismus (63.9+/-18.3) than in other ocular
      diseases (73.5+/-17.8) and normal group (89.4+/-12.0) (divergent validity). The 4
      dimension psychometric analysis was performed by removing 2 items and grouping
      the 18 others in 4 groups. It confirmed the divergent and convergent validity,
      internal consistency and reproducibility of the scale. The results of the
      confirmatory factor analysis were better with the 4 dimension scale than the 2
      dimension scale (adjustment coefficients>0.9). CONCLUSION: We now have access to
      a health related questionnaire in French to quantify the impact of strabismus on
      quality of life and measure the results of treatment.

PMID- 29050926
TI  - [Role of laser peripheral iridotomy in pigmentary glaucoma and pigment dispersion
      syndrome: A review of the literature [French version]].
AB  - PURPOSE: Pigment dispersion syndrome (PSD) is characterized by a structural
      abnormality of the posterior surface of the iris causing contact with the zonular
      fibers. It can lead to an open-angle glaucoma secondary to pigment dispersion
      into the trabecular meshwork. Laser peripheral iridotomy (PI) has been proposed
      as a treatment for pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS)
      by reducing the dispersion of pigment. The goal of this review was to assess the
      effects of PI for PSD and PG. METHODS: We included six randomized controlled
      trials and two cohort studies (286 eyes of 218 participants). Four trials
      included participants with PG, and 4 trials enrolled participants with PSD with
      or without elevated intraocular pressure (IOP). RESULTS: Among patients with PG,
      at an average of 9 months of follow-up, the mean difference in IOP between groups
      was 2.69mmHg less in the PI group (95 % CI: -6.05 to 0.67; 14 eyes). In patients
      with PDS, the average IOP was statistically lower after PI as compared to
      baseline (Student test, t=11.49, P<0.01). With regard to visual field progression
      in participants with GP, after an average follow-up of 28 months, the risk of
      progression was not influenced by PI (RR 1.00 95 %: CI 0.16 to 6.25; 32 eyes). No
      trials that enrolled patients with PSD showed a diminution of the risk of
      glaucoma conversion at mid- and long-term. CONCLUSION: PI decreases the
      biomechanical factor causing contact between the iris and zonular fibers and may
      lower IOP over the long-term. Nevertheless, the effects of PI on visual field
      changes or progression have not been established in PG and PDS. There is no
      scientific evidence as of yet to advocate PI as a treatment for PDS or PG.

PMID- 29050928
TI  - Central corneal thickness assessment after phacoemulsification: Subluxation
      versus Divide-and-Conquer.
AB  - PURPOSE: To compare the impact of two phacoemulsification techniques (subluxation
      versus divide-and-conquer) on postoperative corneal edema at postoperative hour 1
      and day 4. DESIGN: Comparative study. METHOD: Ninety-six consecutive patients
      (110 eyes; 43 men and 53 women, mean age 70.9+/-9.8 years) with equivalent
      cataract grades underwent cataract surgery and were followed up for 6 months. The
      presence of corneal edema was determined using central corneal thickness (CCT).
      CCT was measured preoperatively, and at postoperative hour 1 and day 4. MAIN
      OUTCOME MEASURES: Ultrasound power (US %), duration of ultrasound (TPA),
      effective ultrasound time (TPE), surgical duration and final suture (%). RESULTS:
      Eyes of participants were divided into two phacoemulsification technique groups:
      subluxation (n=50 eyes) and divide-and-conquer (n=60 eyes). Non-inferiority
      analysis revealed similar CCT increases at postoperative hour 1 in both groups,
      with 69.9+/-44.9MUm and 64.4+/-42.9MUm, observed in the subluxation and divide
      and-conquer groups, respectively (P=0.033). TPE was similar in both groups,
      taking 6.2+/-3.4 and 7.3+/-4.5seconds in the subluxation and divide-and-conquer
      groups, respectively (P=0.150). No correlation was seen between TPE and edema at
      postoperative hour 1, or between TPE and day 4 edema. Rate of final suture use
      was similar between the subluxation and divide and conquer groups, at 36% and
      30%, respectively. CONCLUSION: The study findings suggest that cataract surgery
      performed using the subluxation technique does not result in greater CCT than the
      divide-and-conquer technique. CCT appears to normalize by postoperative day 4,
      regardless of the technique used.

PMID- 29050929
TI  - [Orbital rhabdomyosarcoma requiring emergency exenteration for hemostasis in a
      two-year-old: A case report].

PMID- 29050930
TI  - A plea for more practical and clinically applicable criteria defining type 3c
      diabetes.

PMID- 29050932
TI  - Characteristics of patients using specialty medications.
AB  - BACKGROUND: Specialty medications include innovative drugs and biologic agents
      requiring special handling and close monitoring. Although specialty medications
      have been widely used for various chronic conditions, increased use of these
      medications has contributed a growing share of total health care expenditures.
      OBJECTIVE: The aim of this study was to examine patient characteristics related
      to specialty medication use. METHODS: Using Medical Expenditure Panel Survey
      (MEPS) data from 2000 through 2013, this study identified U.S. adults using
      specialty medications. Andersen's Health Services Utilization model was used to
      identify potential factors related to specialty medication use. Associations
      between the variables identified by Andersen's model and specialty medication use
      were analyzed using logistic multilevel modelling. Sampling weights were
      considered and standard errors were adjusted to account for the complex survey
      design. RESULTS: A fully adjusted model suggested that older adults, individuals
      with prescription drug insurance, or those using mail order services were more
      likely to use specialty medications regardless of whether they used traditional
      medications concurrently. Behaviors of using specialty medications were
      positively associated with married and active working status and negatively
      associated with middle or high income and having a usual source of care (visiting
      a doctor's office, clinic, or health center when sick) when comparing individuals
      using traditional medications and those using specialty medications. In addition,
      when comparing individuals using traditional medications with those using both
      specialty medications and traditional medications, behaviors of using specialty
      medications were positively associated with female gender, worse health state,
      and more comorbidities. CONCLUSION: This study identified characteristics of
      patients using specialty medications. Some sociodemographic, economic, and
      clinical factors were related to specialty medication use among U.S. adults.

PMID- 29050931
TI  - Anti-inflammatory drug, leflunomide and its metabolite teriflunomide inhibit
      NSCLC proliferation in vivo and in vitro.
AB  - Lung cancer causes more than 150000 deaths annually in the United States alone,
      of which non-small cell lung cancer (NSCLC) accounts for 80%. Our studies
      demonstrated that NSCLC cells were sensitive to leflunomide and its metabolite
      teriflunomide, a FDA approved drug, which was a well-known immunomodulatory drug
      for relapsing multiple sclerosis (MS). In the present studies, we found first
      time that they displayed anti-tumor activity of NSCLC in vitro and in vivo.
      Potent anti-cancer effects in NSCLC in vitro, including inhibiting NSCLC cells
      viability, arresting cell cycle at the G0/G1 phase, inducing cell apoptosis,
      delaying and suppressing NSCLC cells colony-forming ability and cell motility,
      could be achieved with this agent. Meanwhile, we provided evidence that these
      effects were applicable in vivo by using H460 cells xenograft model in nude mice.
      In addition, to comprehensively clarify the mechanisms of teriflunomide in NSCLC,
      we explored a genome-wide transcriptomic analysis, and found that teriflunomide
      was involved in multiple signaling pathways and cellular processes, such as cell
      cycle, apoptosis, MAPK and p53 signaling pathway. Taken together, the results of
      our studies provided insights into a novel anti-cancer effect of leflunomide and
      teriflunomide on NSCLC and might open new therapeutic avenues for the treatment
      of NSCLC.

PMID- 29050933
TI  - FOXK1 plays an oncogenic role in the development of esophageal cancer.
AB  - Forkhead box k1 (FOXK1) is a member of the FOX class of transcription factors and
      it is dysregulated in many solid tumors including hepatocellular carcinoma,
      gastric cancer, colorectal cancer and prostate cancer. However, the expression
      status of FOXK1 and its clinical significance in esophageal cancer (EC) is still
      uncertain. Our study aimed at investigating the significance of FOXK1 expression
      in human EC and its biological function in the development of EC. We found that
      FOXK1 was overexpressed in EC tissues compared with corresponding non-tumor
      tissues using immunohistochemistry. And high FOXK1 expression was related to poor
      differentiation of EC. The Kaplan-Meier curve indicated that high FOXK1
      expression may result in poor prognosis of EC patients. Furthermore,
      overexpression of FOXK1 in EC9706 cell inhibited cell apoptosis and promoted cell
      proliferation and migration, and suppression of FOXK1 in EC109 cell obtained
      reverse results. Our data suggest that FOXK1 plays an oncogenic role in EC
      pathogenesis and can serve as a therapeutic target for patients with EC.

PMID- 29050934
TI  - Molecular insights into the specific recognition between the RNA binding domain
      qRRM2 of hnRNP F and G-tract RNA: A molecular dynamics study.
AB  - Heterogeneous nuclear ribonucleoprotein F (hnRNP F) controls the expression of
      various genes through regulating the alternative splicing of pre-mRNAs in the
      nucleus. It uses three quasi-RNA recognition motifs (qRRMs) to recognize G-tract
      RNA which contains at least three consecutive guanines. The structures containing
      qRRMs of hnRNP F in complex with G-tract RNA have been determined by nuclear
      magnetic resonance (NMR) spectroscopy, shedding light on the recognition
      mechanism of qRRMs with G-tract RNA. However, knowledge of the recognition
      details is still lacking. To investigate how qRRMs specifically bind with G-tract
      RNA and how the mutations of any guanine to an adenine in the G-tract affect the
      binding, molecular dynamics simulations with binding free energy analysis were
      performed based on the NMR structure of qRRM2 in complex with G-tract RNA.
      Simulation results demonstrate that qRRM2 binds strongly with G-tract RNA, but
      any mutation of the G-tract leads to a drastic reduction of the binding free
      energy. Further comparisons of the energetic components reveal that van der Waals
      and non-polar interactions play essential roles in the binding between qRRM2 and
      G-tract RNA, but the interactions are weakened by the effect of RNA mutations.
      Structural and dynamical analyses indicate that when qRRM2 binds with G-tract
      RNA, both qRRM2 and G-tract maintain stabilized structures and dynamics; however,
      the stability is disrupted by the mutations of the G-tract. These results provide
      novel insights into the recognition mechanism of qRRM2 with G-tract RNA that are
      not elucidated by the NMR technique.

PMID- 29050935
TI  - The L1 adhesion molecule normalizes neuritogenesis in Rett syndrome-derived
      neural precursor cells.
AB  - Therapeutic intervention is an important need in ameliorating the severe
      consequences of Rett Syndrome (RTT), a neurological disorder caused by mutations
      in the X-linked gene methyl-CpG-binding protein-2 (MeCP2). Following previously
      observed morphological defects in induced pluripotent stem cell (iPSC)-derived
      neurons obtained from female RTT patients, we hypothesized that transfection with
      the L1 cell adhesion molecule (L1) could contribute to normalizing a pathological
      male cell system bearing a nonsense mutation of MeCP2. We found a decreased
      expression of L1 in RTT iPSCs-derived neural precursor cells (RTT NPCs) and
      decreased neuritogenesis. Expression of wild-type MeCP2 in RTTNPCs revealed a
      positive correlation between the levels of MeCP2 and L1, and normalization of
      cell survival. Expression of L1 in RTTNPCs enhanced neuritogenesis and soma size.
      Knock-down of MeCP2 in wild type NPCs reduced neuritogenesis. L1 expression is
      regulated by the MeCP2 promoter. These results suggest that a deficiency in L1
      may partially account for RTT phenotypes.

PMID- 29050936
TI  - TbetaRIII is induced by TCR signaling and downregulated in FoxP3+ regulatory T
      cells.
AB  - TGF-beta type III receptor (TbetaRIII) is a co-receptor for TGFbeta family
      members required for high-affinity binding of these ligands to their receptors,
      potentiating their cellular functions. TGF-betas, Bone Morphogenetic Proteins
      (BMP2/4) and Inhibins/Activins regulate different checkpoints during T cell
      differentiation. We have previously reported that TbetaRIII modulates T cell
      development by protecting developing thymocytes from apoptosis, however the role
      of this co-receptor in peripheral lymphocytes still remains elusive. Here we
      describe a detailed characterization of TbetaRIII expression in murine and human
      lymphocyte subpopulations demonstrating that this co-receptor is significantly
      expressed in T but not B lymphocytes and among them, preferentially expressed on
      naive and central memory T cells. TbetaRIII was upregulated after TCR
      stimulation, in parallel to other early activation markers. In contrast, natural
      and induced Tregs downregulated TbetaRIII in association with FoxP3 upregulation.
      Finally, anti-TbetaRIII blocking experiments demonstrated that TbetaRIII promotes
      TGFbeta-dependent iTreg conversion in vitro, and suggest that this co-receptor
      may be involved in modulating peripheral T cell tolerance and could be considered
      as a potential target to boost T cell immune responses.

PMID- 29050937
TI  - Integrated expression profiling of potassium channels identifys KCNN4 as a
      prognostic biomarker of pancreatic cancer.
AB  - Dysregulated potassium (K+) channels have previously been shown to promote the
      development and progression of many types of cancers. Meanwhile, K+ channels are
      particularly important in regulating the endocrine and exocrine functions of
      pancreas. However, the expression pattern and prognostic significance of K+
      channels in pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this
      study, by screening a GEO dataset containing 36 microdissected PDAC and matching
      normal pancreatic tissue samples, four differentially expressed K+ channels
      (KCNJ5, KCNJ16, KCNN4 and KCNK1) were identified in PDAC. by immunohistochemical
      analysis of pancreatic tissue sections from Pdx1-Cre; LSL-KrasG12D/+ mice (KC),
      Pdx1-Cre; LSL-KrasG12D/+; LSL-Trp53R172H/+ mice (KPC) and human PDAC tissue
      microarrays, we found that Ca2+-activated K+ channel KCNN4 was significantly
      elevated in pancreatic intraepithelial neoplasia (PanIN) and PDAC epithelia
      compared with untransformed pancreas tissues. Higher epithelial KCNN4 expression
      was closely correlated with advanced TNM stages and predicted a poor prognosis in
      patients with PDAC. Elevated KCNN4 expression was significantly associated with
      shorter survival in univariable and multivariable analyses. Collectively, the
      identification of expression pattern of K+ channels in PDAC and its precursor
      PanIN demonstrates the importance of KCNN4 channel during the malignant
      transformation of PDAC. On the basis of the prognostic signals from two
      independent cohorts, KCNN4 should be considered as a promising therapeutic
      target.

PMID- 29050938
TI  - Tumor suppressive role of miR-1224-5p in keloid proliferation, apoptosis and
      invasion via the TGF-beta1/Smad3 signaling pathway.
AB  - The molecular mechanism of the pathogenesis of keloids is still not known and the
      clinical management of keloids remains challenging. MiRNA (microRNA) is a novel
      class of small regulatory RNAs that has emerged as key post-transcriptional
      regulators of gene expression. MiRNAs participate in diverse biological processes
      of various skin diseases and function as key regulators in the occurrence and
      development of tumors. The purpose of this study was to investigate the
      involvement of miRNAs in keloid pathogenesis. We performed miRNA microarray
      analysis to compare miRNA expression between keloid and normal skin samples. We
      found that 46 miRNAs were upregulated and 28 miRNAs were downregulated in keloid
      compared with normal skin samples. We focused on miR-1224-5p, which has been
      reported to function in cancers, although the expression and mechanism of miR
      1224-5p in keloids remain to be explored. Overexpression of miR-1224-5p led to
      inhibition of keloid fibroblast proliferation, promotion of apoptosis and
      decrease of migration and invasion. Our results suggest that downregulation of
      miR-1224-5p may be one of the mechanisms involved in the occurrence and
      development of keloids.

PMID- 29050939
TI  - C6 glioma-conditioned medium induces malignant transformation of mesenchymal stem
      cells: Possible role of S100B/RAGE pathway.
AB  - Mesenchymal stem cells (MSCs) have been widely studied as an attractive
      therapeutic agent for the treatment of tumors. However, the adverse effects of
      the tumor paracrine factors who affect MSCs are still unclear. In this study, we
      report for the first time that C6 glioma-conditioned medium (GCM) induces
      malignant transformation of MSCs. In contrast to MSCs, the transformed
      mesenchymal stem cells (TMCs) exhibited tumor cell characterizations in vitro and
      highly tumorigenic in vivo. Furthermore, GCM and recombinant S100B increased
      receptor for advanced glycation end products (RAGE) and its downstream Akt1,
      STAT3 genes expression as well as phosphorylation and transcriptional activation.
      Finally, blockage of S100B-RAGE interaction by RAGE inhibitor FPS-ZM1 attenuated
      GCM and S100B-induced Akt1, STAT3 activation, abolished its cell proliferation,
      migration and invasion actions. Together, these results suggest that the RAGE
      pathway may play a possible role in malignant transformation procedure of MSCs,
      and that this process may be mediated through S100B.

PMID- 29050940
TI  - Long non-coding RNA-422 acts as a tumor suppressor in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most frequent cancer in numerous of
      countries worldwidely. The initiation and progression of CRC is an extremely
      complex process, and have been suggested a correlation with Long non-coding RNAs
      (lncRNAs). Our results showed that lncRNA-422(ENST00000415820) significantly
      downregulated in the tissues and serum of CRC patients, and is closely associated
      with the poor prognosis. Then gain or loss of lncRNA-422 models in SW480 and
      SW620cells were established. The results showed that lncRNA-422 overexpression
      inhibited cell proliferation, migration, and invasion. Knockdown of lncRNA-422
      promoted tumorigensis. Western blot and qRT-PCR were performed to examine the
      activity of the PI3K/AKT/mTOR pathway in CRC cells after alternation of lncRNA
      422. Results showed that lncRNA-422 acts as a tumor suppressor by PI3K/AKT/mTOR
      pathway in CRC.

PMID- 29050941
TI  - Mahanine enhances the glucose-lowering mechanisms in skeletal muscle and
      adipocyte cells.
AB  - Insulin resistance is a major defect underlying type 2 diabetes development.
      Skeletal muscle tissue and adipocyte tissue are the major sites of postprandial
      glucose disposal, and enhancing glucose uptake into this tissue may decrease
      insulin resistance in type 2 diabetes patients. Mahanine (3,11-dihydro-3,5
      dimethyl-3-(4-methyl-3-pentenyl)pyrano[3,2-a]carbazol-9-ol) has been reported to
      be a major bioactive carbazole alkaloid that has many biological activities
      including antitumor, anti-inflammatory, antioxidant and anti-diabetic activities.
      However, the molecular mechanism and signaling pathways mediating the anti
      diabetic effects of mahanine require further investigation. Therefore, the aim of
      this study was to investigate the effects of mahanine, a carbazole alkaloid from
      Murraya koenigii, on glucose uptake and glucose transporter 4 (GLUT4)
      translocation in skeletal muscle and adipocyte cells. Mahanine treatment promoted
      a dose dependent increased in glucose uptake in L6 myotubes and adipocyte cells
      via activation of the Akt signaling pathway. Mahanine induced Akt-activation was
      reversed by co-treatment with wortmannin, an Akt inhibitor. Moreover, it was
      found that mahanine significantly enhanced GLUT4 translocation to the plasma
      membrane in L6 myotubes. These results suggest that increased activation of the
      Akt signaling pathway lead to increased plasma membrane GLUT4 content and
      increased glucose uptake. These data strongly suggest that mahanine has anti
      diabetic potential for treating diabetes.

PMID- 29050942
TI  - Low dose administration of Bisphenol A induces liver toxicity in adult rats.
AB  - BACKGROUND: Bisphenol A (BPA) is one of the most widely used chemicals, often
      used in epoxy resins, health products and colors. This study aims to investigate
      the effect of various doses of BPA on hepatotoxicity in rats. METHOD: This
      experimental study was conducted using 20 male adult Wistar rats older than 2
      months weighing 150-200 g. (5, 25 and 125 MUg/kg) BPA was administered by gavage
      for 35 consecutive days. The animals were weighed at the beginning and the end of
      the experiment. The level of aspartate aminotransferase, alanine aminotransferase
      and alkaline phosphatase were determined using colorimetric method. The liver
      tissue was kept in the freezer at -80  degrees C for histological studies.
      FINDING: The body weight of rats receiving BPA decreased significantly compared
      to control group and this weight loss was more evident at doses of 25 and 125
      MUg/kg (p < 0.001). Results of the study demonstrated that the level of ALP and
      AST decreases significantly (p < 0.001 and p < 0.05, respectively), while the
      level of ALT did not change. The results that BPA significantly decreased Beta-2
      protein and increased Gama protein serum levels in rats (p < 0.01). CONCLUSION:
      Results of this study demonstrated that BPA increase gamma globulin protein
      levels and decreases the level of alkaline phosphatase, aspartate
      aminotransferase and serum protein beta2 and causes weight loss in rats after
      treatment. This research also demonstrated that the toxic effect of BPA on liver
      is induced by oxidative stress.

PMID- 29050943
TI  - mir-67 regulates P. aeruginosa avoidance behavior in C. elegans.
AB  - Pathogen avoidance behaviors are found throughout the animal kingdom and are
      important for animal's survival in nature. As a free-living nematode, C. elegans
      is exposed to a variety of microorganisms, including toxic or pathogenic
      bacteria, in soil. C. elegans can develop efficient avoidance responses to
      pathogenic bacteria to minimize the infection risk. However, the role of
      microRNAs (miRNAs) in pathogen avoidance in C. elegans remains unclear. In this
      report, we showed that the miRNA mir-67 was involved in a behavioral avoidance
      response to P. aeruginosa PA14. Exposure to P. aeruginosa PA14 induced the
      expression of mir-67 in worms. mir-67(n4899) mutants exhibited a reduced ability
      to avoid P. aeruginosa PA14. By combining quantitative proteomic analysis with
      miRNA target prediction algorithms, we identified SAX-7/L1CAM, which is
      transmembrane cell adhesion receptor molecule, as the target of mir-67. Silencing
      of sax-7 by RNAi on mir-67 mutants rescued avoidance behavioral. Our data
      demonstrate that the mir-67-SAX-7 pathway modulate the behavioral avoidance
      response to pathogens, thus providing a new perspective in the role of miRNAs in
      host-microbe interactions.

PMID- 29050944
TI  - Crystal structures of Aflatoxin-oxidase from Armillariella tabescens reveal a
      dual activity enzyme.
AB  - Aflatoxin-oxidase (AFO), a newly discovered oxidase isolated from Armillariella
      tabescens, was reported to perform aflatoxin B1 (AFB1) detoxification through
      breaking the bisfuran ring of AFB1. However, based on sequence alignment, we
      found that AFO shares high sequence identities with dipeptidyl peptidase III (DPP
      III) family members. To understand the functions of AFO, we determined its
      crystal structures in the absence and presence of zinc, copper ion, and employed
      HPLC to test if AFO could cleave the substrates of DPP III. Our structures reveal
      that AFO contains the classic DPP III activity center and the HPLC results
      further confirm that AFO possesses the dipeptidyl peptidase activity. Therefore,
      AFO should belong to DPP III family. Interestingly, unlike reported classic DPP
      III structure that has a large domain movement upon substrate binding, the AFO
      structures all adopt the closed conformation, independent of substrate binding.
      This conformation characteristic of AFO may be related to its enzyme activities.
      Taken together, our results demonstrate that AFO is a dual activity enzyme with
      both aflatoxin-oxidase and dipeptidyl peptidase activities and its unique
      conformation feature expands our understanding on the mode of reaction for this
      enzyme family.

PMID- 29050945
TI  - Aptamers as therapeutic middle molecules.
AB  - Therapeutic molecules can be classified as low-, middle- and high-molecular
      weight drugs depending on their molecular masses. Antibodies represent high
      molecular weight drugs and their clinical applications have been developing
      rapidly. Aptamers, on the other hand, are middle-molecular weight molecules that
      are short, single-stranded nucleic acid sequences that are selected in vitro from
      large oligonucleotide libraries based on their high affinity to a target
      molecule. Hence, aptamers can be thought of as a nucleic acid analog to
      antibodies. However, several viewpoints hold that the potential of aptamers
      arises from interesting characteristics that are distinct from, or in some cases,
      superior to those of antibodies. Recently, therapeutic middle molecules gain
      considerable attention as protein-protein interaction (PPI) inhibitors. This
      review summarizes the recent achievements in aptamer development in our
      laboratory in terms of PPI and non-PPI inhibitors.

PMID- 29050946
TI  - Specific elements of thoracic wound management.
AB  - Damage control for thoracic trauma combines definitive and temporary surgical
      gestures specifically adapted to the lesions present. A systematic assessment of
      all injuries to prioritize the specific lesions and their treatments constitutes
      the first operative stage. Packing and temporary closure have a place in the care
      of chest injuries.

PMID- 29050948
TI  - Detection of Malaria Parasites After Treatment in Travelers: A 12-months
      Longitudinal Study and Statistical Modelling Analysis.
AB  - The rapid clearance of malaria parasite DNA from circulation has widely been
      accepted as a fact without being systemically investigated. We assessed the
      persistence of parasite DNA in travelers treated for Plasmodium falciparum
      malaria in a malaria-free area. Venous blood was collected at the time of
      admission and prospectively up to one year. DNA and RNA were extracted and
      analyzed using species-specific and gametocyte-specific real-time PCR as well as
      merozoite surface protein 2 (msp2)-PCR. In 31 successfully treated individuals,
      asexual parasites were seen by microscopy until two days after treatment, whereas
      parasite DNA was detected by msp2- and species-specific PCR up to days 31 and 42,
      respectively. Statistical modelling predicted 26% (+/-0.05 SE) species-specific
      PCR positivity until day 40 and estimated 48days for all samples to become PCR
      negative. Gametocytes were detected by microscopy and PCR latest two days after
      treatment. CT values correlated well with microscopy-defined parasite densities
      before but not after treatment started. These results reveal that PCR positivity
      can persist several weeks after treatment without evidence of viable sexual or
      asexual parasites, indicating that PCR may overestimate parasite prevalence after
      treatment.

PMID- 29050949
TI  - High frequency of trypanosomatids in gallery forest bats of a Neotropical
      savanna.
AB  - Bats are well-known hosts of trypanosomatids, though information about their role
      as reservoirs of these protozoans in the Brazilian savanna is poorly known. We
      aimed to analyze the occurrence of trypanosomatid species in bats occurring in
      remnants of gallery forests of Brasilia, Federal District of Brazil. We sampled
      bats using mist nets in six sites, and we collected blood, wing fragments and
      oral swab samples from all captured individuals. Trypanosomatids were identified
      in the captured bats through sequencing of the SSUrRNA region and kDNA qPCR. We
      found no parasite in blood smears of 146 individuals of 14 species captured, but
      blood cultures were positive for nine bats. We detected trypanosomatids
      molecularly in 111 (76%) specimens of all bat species in the studied areas. Most
      of the infected bats had Leishmania-like DNA detected in blood and swab samples
      of the oral mucosa. We distinguished three species of Trypanosoma (Trypanosoma
      dionisii, T. rangeli and T. cruzi) in Carollia perspicillata. SSUrRNA PCR of oral
      samples is a non-invasive and practical method for identification of
      trypanosomatid species in bats. Our results support our belief that bats could be
      potential reservoirs for Trypanosoma and Leishmania-like species in the enzootic
      cycle of these parasites in gallery forests of the Brazilian Cerrado biome.

PMID- 29050947
TI  - Cyclic AMP-Responsive Element-Binding Protein (CREB) is Critical in Autoimmunity
      by Promoting Th17 but Inhibiting Treg Cell Differentiation.
AB  - The molecular mechanisms that govern differential T cell development into pro
      inflammatory Th17 vs. regulatory T (Treg) cells remain unclear. Here, we show
      that selective deletion of CREB in T cells or Th17 cells impaired Th17 cell
      differentiation in vitro and in vivo, and led to resistance to autoimmune
      diseases. Mechanistically, CREB, activated by CD3-PKC-Theta signaling, plays a
      key role in regulating Th17 cell differentiation, at least in part through
      directly binding to the Il17-Il17f gene locus. Unexpectedly, although dispensable
      for FOXP3 expression and for the homeostasis and suppressive function of thymus
      derived Treg cells, CREB negatively regulates the survival of TGF-beta-induced
      Treg cells, and deletion of CREB resulted in increased FOXP3+ Treg cells in the
      intestine and protection in a colitis model. Thus, CREB is critical in autoimmune
      diseases by promoting Th17 cell and inhibiting de novo Treg cell generation.

PMID- 29050950
TI  - Modeling and comparative study of the spread of zoonotic visceral leishmaniasis
      from Northern to Central Tunisia.
AB  - During the last twenty years, zoonotic visceral leishmaniasis (ZVL) spread from
      the north characterized by humid, sub-humid, and semi-arid bio-climates to the
      arid areas located in Central Tunisia. In order to understand the eco
      epidemiological factors involved in the distribution of ZVL, both a sero
      epidemiological and an entomological investigation were performed in two
      governorates situated in two different bio-geographical areas: Bizerte in the
      north and Kairouan in the center. A mathematical model for transmission of ZVL
      was built, describing the disease dynamic in these areas. Among 108 sera
      collected from clinically healthy owned dogs used for guarding houses in the
      governorate of Bizerte and tested for anti-L. infantum antibodies by indirect
      immune-fluorescence antibody test (IFAT), 8.3% were positive. From a total of 191
      serum samples collected from clinically healthy owned dogs used for guarding
      houses in the governorate of Kairouan and tested for anti-L. infantum antibodies
      by IFAT, 26.7% were sero-positive. The cumulative incidences of ZVL in humans in
      the governorates of Bizerte and Kairouan were 39.17/100,000 and 0.2/100,000
      inhabitants, respectively. The infection rates of sand flies with Leishmania DNA
      in the governorate of Bizerte and Kairouan were 3.8% and 9.4%, respectively. It
      is important to point out that ZVL epidemic in humans is preceded or concomitant
      to a high prevalence of Leishmania infantum in dogs and in sand flies. The model
      showed also a non-linear relationship between dog infection and ZVL in humans.
      These results suggest an important force of infection (R0) in emerging foci such
      as the governorate of Kairouan leading to an increased incidence of ZCL in
      humans. A high prevalence of L. infantum in dogs will result in high prevalence
      in the vector and obviously high probability to infect human; that it is a key
      factor for triggering transmission to humans, and subsequently it is an important
      parameter in the control of ZVL transmission.

PMID- 29050951
TI  - Microinjection of baclofen and CGP7930 into the ventral tegmental area suppresses
      alcohol self-administration in alcohol-preferring rats.
AB  - Systemic administration of the orthosteric agonist, baclofen, and several
      positive allosteric modulators (PAMs) of the GABAB receptor has repeatedly been
      reported to decrease operant oral alcohol self-administration in rats. The aim of
      the present study was to evaluate the contribution of the mesolimbic dopamine
      system to the reducing effect of baclofen and GABAB PAMs on the reinforcing
      properties of alcohol. To this end, baclofen or the GABAB PAM CGP7930 were
      microinjected into the ventral tegmental area (VTA) of selectively bred,
      Sardinian alcohol-preferring (sP) rats trained to self-administer alcohol.
      Baclofen (0, 0.03, 0.1, and 0.3 MUg) or CGP7930 (0, 5, 10, and 20 MUg) were
      microinjected via indwelling unilateral guide cannula aiming at the left
      hemisphere of the VTA. Treatment with baclofen resulted in a dose-related
      suppression of the number of lever-responses for alcohol and the amount of self
      administered alcohol. No dose of baclofen altered rat motor-performance,
      evaluated by the inverted screen test immediately before the self-administration
      session. Treatment with CGP7930 halved the number of lever-responses for alcohol
      and amount of self-administered alcohol, with no effect on rat motor-performance.
      Site-specificity was investigated testing the effect of microinjection of
      baclofen and CGP7930 into the left hemisphere of deep mesencephalic nucleus:
      compared to vehicle, neither 0.3 MUg baclofen nor 20 MUg CGP7930 altered lever
      responding for alcohol and amount of self-administered alcohol. Collectively, the
      results of the present study suggest the involvement of GABAB receptors located
      in the VTA in the mediation of alcohol reinforcing properties in sP rats. This
      article is part of the "Special Issue Dedicated to Norman G. Bowery".

PMID- 29050952
TI  - A research coding method to evaluate medical clinicians conduct of behavioral
      health care in patients with unexplained symptoms.
AB  - OBJECTIVE: Develop a reliable coding method of a Behavioral Health Treatment
      Model for patients with Medically Unexplained Symptoms (BHTM-MUS). METHODS: Two
      undergraduates trained for 30h coded videotaped interviews from 161 resident
      simulated patient (SP) interactions. Trained on 45 videotapes, coders coded 33
      (20%) of 161 study set tapes for the BHTM-MUS. Guetzkow's U, Cohen's Kappa, and
      percent of agreement were used to measure coders' reliability in unitizing and
      coding residents' skills for eliciting: education and informing (4 yes/no items),
      motivating (2), treatment statements (5), commitment and goals (2), negotiates
      plan (8), non-emotion patient-centered skills (4), and patient-centered emotional
      skills (8). RESULTS: 60 items were dichotomized a priori from analysis of the
      BHTM-MUS and were reduced to 33 during training. Guetzkow's U ranged from .00 to
      .082. Kappa ranged from 0.76 to 0.97 for the 7 variables and 33 individual items.
      The overall kappa was 0.87, and percent of agreement was 95.7%. Percent of
      agreement by item ranged from 85 to 100%. CONCLUSIONS: A highly reliable coding
      method is recommended to evaluate medical clinicians' behavioral care skills in
      patients with unexplained symptoms. PRACTICE IMPLICATIONS: A way to rate
      behavioral care in patients with unexplained symptoms.

PMID- 29050953
TI  - Dual-energy CT based proton range prediction in head and pelvic tumor patients.
AB  - BACKGROUND AND PURPOSE: To reduce range uncertainty in particle therapy, an
      accurate computation of stopping-power ratios (SPRs) based on computed tomography
      (CT) is crucial. Here, we assess range differences between the state-of-the-art
      CT-number-to-SPR conversion using a generic Hounsfield look-up table (HLUT) and a
      direct patient-specific SPR prediction (RhoSigma) based on dual-energy CT (DECT)
      in 100 proton treatment fields. MATERIAL AND METHODS: For 25 head-tumor and 25
      prostate-cancer patients, the clinically applied treatment plan, optimized using
      a HLUT, was recalculated with RhoSigma as CT-number-to-SPR conversion. Depth-dose
      curves in beam direction were extracted for both dose distributions in a regular
      grid and range deviations were determined and correlated to SPR differences
      within the irradiated volume. RESULTS: Absolute (relative) mean water-equivalent
      range shifts of 1.1mm (1.2%) and 4.1mm (1.7%) were observed in the head-tumor and
      prostate-cancer cohort, respectively. Due to the case dependency of a generic
      HLUT, range deviations within treatment fields strongly depend on the tissues
      traversed leading to a larger variation within one patient than between patients.
      CONCLUSIONS: The magnitude of patient-specific range deviations between HLUT and
      the more accurate DECT-based SPR prediction is clinically relevant. A clinical
      application of the latter seems feasible as demonstrated in this study using
      medically approved systems from CT acquisition to treatment planning.

PMID- 29050954
TI  - The TRENDY multi-center randomized trial on hepatocellular carcinoma - Trial QA
      including automated treatment planning and benchmark-case results.
AB  - BACKGROUND AND PURPOSE: The TRENDY trial is an international multi-center phase
      II study, randomizing hepatocellular carcinoma (HCC) patients between
      transarterial chemoembolization (TACE) and stereotactic body radiation therapy
      (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality
      assurance (QA) program, including prospective plan feedback based on automated
      treatment planning, is described and results are reported. MATERIALS AND METHODS:
      Scans of a single patient were used as a benchmark case. Contours submitted by
      nine participating centers were compared with reference contours. The subsequent
      planning round was based on a single set of contours. A total of 20 plans from
      participating centers, including 12 from the benchmark case, 5 from a clinical
      pilot and 3 from the first study patients, were compared to automatically
      generated VMAT plans. RESULTS: For the submitted liver contours, Dice Similarity
      Coefficients (DSC) with the reference delineation ranged from 0.925 to 0.954. For
      the GTV, the DSC varied between 0.721 and 0.876. For the 12 plans on the
      benchmark case, healthy liver normal-tissue complication probabilities (NTCPs)
      ranged from 0.2% to 22.2% with little correlation between NCTP and PTV-D95% (R2 <
      0.3). Four protocol deviations were detected in the set of 20 treatment plans.
      Comparison with co-planar autoVMAT QA plans revealed these were due to too high
      target dose and suboptimal planning. Overall, autoVMAT resulted in an average
      liver NTCP reduction of 2.2 percent point (range: 16.2 percent point to -1.8
      percent point, p = 0.03), and lower doses to the healthy liver (p < 0.01) and
      gastrointestinal organs at risk (p < 0.001). CONCLUSIONS: Delineation variation
      resulted in feedback to participating centers. Automated treatment planning can
      play an important role in clinical trials for prospective plan QA as suboptimal
      plans were detected.

PMID- 29050955
TI  - Palliative radiation therapy in the last 30 days of life: A systematic review.
AB  - PURPOSE: To investigate the utilization of palliative radiation therapy (RT),
      predictors for the use of RT, and symptom palliation following RT during the last
      30 days of life through systemic review of literature. MATERIALS/METHODS: A
      systematic search of available medical literature databases was performed on
      patients receiving palliative RT in the last 30 days of life. A total of 18
      studies were evaluated. RESULTS: The overall palliative RT utilization rates
      during the last month of life were in the range of 5-10% among patients who died
      of cancer and 9-15.3% of patients who received palliative RT. The most commonly
      used regimen was 30 Gy in 10 fractions (36-90%). Single fraction RT utilization
      ranged from 0% to 59%. ECOG performance status 3-4 was significantly associated
      with patients receiving RT in the last 30 days of life and shorter survival.
      Twenty-six percent of patients who survived less than 1 month were reported to
      show symptom palliation following RT. CONCLUSION: Palliative RT was performed in
      approximately 10% of patients who died of cancer near their end of life, with the
      most commonly used regimen of 30 Gy in 10 fractions. This study suggests that
      greater use of shorter or single fraction regimens may be beneficial, especially
      in patients with poor performance status.

PMID- 29050956
TI  - Lung toxicity after radiation in childhood: Results of the International Project
      on Prospective Analysis of Radiotoxicity in Childhood and Adolescence.
AB  - BACKGROUND AND PURPOSE: This study presents the evaluation of acute and late
      toxicities of the lung in children and adolescents after irradiation in terms of
      dose-volume effects. MATERIALS AND METHODS: Irradiated children and adolescents
      in Germany have prospectively been documented since 2001 in the "Registry for the
      Evaluation of Side-Effects after Radiotherapy in Childhood and Adolescence
      (RiSK)"; in Sweden since 2008 in the RADTOX registry. RESULTS: Up to April 2012,
      1,392 children were recruited from RiSK, and up to June 2013, 485 from the RADTOX
      registry. Of these patients, 295 were irradiated to the lung. Information about
      acute toxicity was available for 228 patients. 179 patients have been documented
      concerning late toxicity (>=grade 1: n = 28). The acute toxicity rate was
      noticeably higher in children irradiated with 5-20Gy (p < 0.05). In the
      univariate analysis, a shorter time until late toxicity was noticeably associated
      with irradiation with 5-15Gy (p < 0.05). CONCLUSION: Acute and late toxicities
      appear to be correlated with higher irradiation volumes and low doses. Our data
      indicate that similar to the situation in adult patients, V5, V10, V15 and V20
      should be kept as low as possible (e.g., at least V5 < 50%, V10 and V15 < 35% and
      V20 < 30%) in children and adolescents to lower the risk of toxicity.

PMID- 29050957
TI  - Heart dosimetric analysis of three types of cardiac toxicity in patients treated
      on dose-escalation trials for Stage III non-small-cell lung cancer.
AB  - BACKGROUND AND PURPOSE: To assess associations between radiation dose/volume
      parameters for cardiac subvolumes and different types of cardiac events in
      patients treated on radiation dose-escalation trials. MATERIAL AND METHODS:
      Patients with Stage III non-small-cell lung cancer received dose-escalated
      radiation (median 74 Gy) using 3D-conformal radiotherapy on six prospective
      trials from 1996 to 2009. Volumes analyzed included whole heart, left ventricle
      (LV), right atrium (RA), and left atrium (LA). Cardiac events were divided into
      three categories: pericardial (symptomatic effusion and pericarditis), ischemia
      (myocardial infarction and unstable angina), and arrhythmia. Univariable
      competing risks analysis was used. RESULTS: 112 patients were analyzed, with
      median follow-up 8.8 years for surviving patients. Nine patients had pericardial,
      seven patients had ischemic, and 12 patients had arrhythmic events. Pericardial
      events were correlated with whole heart, RA, and LA dose (eg, heart-V30
      [p=0.024], RA-V30 [p=0.013], and LA-V30 [p=0.001]), but not LV dose. Ischemic
      events were correlated with LV and whole heart dose (eg, LV-V30 [p=0.012], heart
      V30 [p=0.048]). Arrhythmic events showed borderline significant associations with
      RA, LA, and whole heart dose (eg, RA-V30 [p=0.082], LA-V30 [p=0.076], heart-V30
      [p=0.051]). Cardiac events were associated with decreased survival on univariable
      analysis (p=0.008, HR 2.09), but only disease progression predicted for decreased
      survival on multivariable analysis. CONCLUSIONS: Cardiac events were
      heterogeneous and associated with distinct heart subvolume doses. These data
      support the hypothesis of distinct etiologies for different types of radiation
      associated cardiotoxicity.

PMID- 29050958
TI  - Metal artefact reduction for accurate tumour delineation in radiotherapy.
AB  - BACKGROUND AND PURPOSE: Two techniques for metal artefact reduction for computed
      tomography were studied in order to identify their impact on tumour delineation
      in radiotherapy. MATERIALS AND METHODS: Using specially designed phantoms
      containing metal implants (dental, spine and hip) as well as patient images, we
      investigated the impact of two methods for metal artefact reduction on (A) the
      size and severity of metal artefacts and the accuracy of Hounsfield Unit (HU)
      representation, (B) the visual impact of metal artefacts on image quality and (C)
      delineation accuracy. A metal artefact reduction algorithm (MAR) and two types of
      dual energy virtual monochromatic (DECT VM) reconstructions were used separately
      and in combination to identify the optimal technique for each implant site.
      RESULTS: The artefact area and severity was reduced (by 48-76% and 58-79%, MAR
      and DECT VM respectively) and accurate Hounsfield-value representation was
      increased by 22-82%. For each energy, the observers preferred MAR over non-MAR
      reconstructions (p < 0.01 for dental and hip cases, p < 0.05 for the spine case).
      In addition, DECT VM was preferred for spine implants (p < 0.01). In all cases,
      techniques that improved target delineation significantly (p < 0.05) were
      identified. CONCLUSIONS: DECT VM and MAR techniques improve delineation accuracy
      and the optimal of reconstruction technique depends on the type of metal implant.

PMID- 29050959
TI  - Sequential proton boost after standard chemoradiation for high-grade glioma.
AB  - PURPOSE: To retrospectively assess the feasibility and safety of a sequential
      proton boost following conventional chemoradiation in high-grade glioma (HGG).
      METHOD AND MATERIALS: Sixty-six consecutive patients with HGG were treated with
      50.0 Gy photons (50.0-50.4 Gy) in 2.0 Gy (1.8-2.0 Gy) fractions, followed by a
      proton boost with 10 Gy equivalent (Gy(RBE)) in 2.0 Gy(RBE) fractions. Patients
      were matched one to one with 66 patients with HGG undergoing conventional
      radiation therapy (RT) with 60.0 Gy photons (59.4-60.0 Gy) in 2.0 Gy fractions
      (1.8-2.0 Gy). Matching criteria were age, WHO grade, Karnofsky's performance
      status, PTV size, temozolomide therapy (each p > 0.1). The study assessed
      progression-free survival (PFS), overall survival (OS), acute treatment-related
      toxicity (CTCAE v.4.03) and pseudoprogression (RANO criteria). RESULTS: Median
      PFS and OS were similar in both treatment groups (bimodality RT, PFS: 8.8 months
      [2-32 months], OS 19.1 months [4-41 months]; photon-only RT, PFS: 7.2 months [2
      39 months], 20.9 months [3-53 months]; p = 0.430 and p = 0.125). The median PTV
      of the proton boost was significantly smaller than the photon plan PTVs (each p <
      0.001). Acute toxicity was mild. Toxicity >=grade 2 was observed in 6 patients
      (9%) receiving bimodality RT and 9 patients (14%) receiving photon-only RT. Two
      types of severe adverse events (CTCAE grade 3) occurred solely in the photon-only
      group: severe increase in intracranial pressure (5%); and generalized seizures
      (3%). Pseudoprogression was rare, occurring on average 6 weeks after
      radiotherapy, and was balanced in both treatment groups (n = 4 each; 8%).
      CONCLUSION: Delivering a proton boost to significantly smaller target volumes
      when compared to photon-only plans, yielded comparable progression and survival
      rates at lower CTCAE grade 3 acute toxicity rates. Pseudoprogression occurred
      rarely and evenly distributed in both treatment groups. Thus, bimodality RT was
      at least equivalent regarding outcome and potentially superior with respect to
      toxicity in patients with HGG. SUMMARY: Treating patients with HGG with 50.0 Gy
      photons in 2.0 Gy fractions, followed by a proton boost with 10 Gy(RBE) in 2.0
      Gy(RBE) fractions, is safe and feasible. Severe radiation-induced acute toxicity
      and pseudoprogression were rare in both treatment groups. Therefore, in this
      clinical setting, combined proton radiotherapy might be beneficial in terms of
      further risk reduction for treatment-related side effects. Interestingly,
      treatment volume reduction using a proton boost led to comparable survival and
      progression rates with decreased severe treatment-related toxicity compared to
      conventional photon radiotherapy.

PMID- 29050960
TI  - Mapping patterns of locoregional recurrence following contemporary treatment with
      radiation therapy for breast cancer: A multi-institutional validation study of
      the ESTRO consensus guideline on clinical target volume.
AB  - BACKGROUND AND PURPOSE: To validate the ESTRO guideline on clinical target volume
      (CTV) delineation for breast cancer using a multi-centre dataset. MATERIALS AND
      METHODS: Patients with axial imaging of gross locoregional recurrence (LRR) were
      identified from 10 participating institutions. All patients received RT, albeit
      not to all regional node. The location of LRR was transferred to the
      corresponding area on representative axial computed tomography images and
      compared with ESTRO-CTV. RESULTS: The locations of LRRs in 234 patients with 337
      recurrence lesions were mapped. The ESTRO-CTV encompassed 97.6% of all LRRs,
      except in lymph node level 4 and the pectoralis muscle. Although 8.8% of level 4
      failures occurred outside the ESTRO-CTV, cranial to the subclavian artery, all
      nodes were located within 6 mm cranially. Another 20% occurred posterolateral to
      anterior scalene muscles; however, 11/16 cases had simultaneous multiple lymph
      node recurrences, and 8/16 initially had N2-3 tumours. Local recurrence at the
      pectoralis muscle was prominent in patients undergoing mastectomy but not breast
      conservation surgery (28% vs. 2.9%, P = .001). CONCLUSIONS: Our mapping data
      demonstrated that the ESTRO-CTV, with some considerations, successfully
      encompassed most LRRs in patients undergoing contemporary management, thus
      validating ESTRO-CTV to be valuable for highly conformal radiation therapy
      techniques.

PMID- 29050961
TI  - Simple strategies to enhance discovery of acetylation post-translational
      modifications by quadrupole-orbitrap LC-MS/MS.
AB  - Enzyme-dependent post-translational modifications (PTMs) mediate the cellular
      regulation of proteins and can be discovered using proteomics. However, even
      where the peptides of interest can be enriched for analysis with state-of-the-art
      LC-MS/MS tools and informatics, only a fraction of peptide ions can be identified
      confidently. Thus, many PTM sites remain undiscovered and unconfirmed. In this
      minireview, we use a case study to discuss how the use of inclusion lists,
      turning off isotopic exclusion, and manual validation significantly increased
      depth of coverage, facilitating discovery of acetylation sites in targets of an
      acetyltransferase virulence factor. These underutilized strategies have the
      potential to help answer many mechanistic biological questions that large-scale
      proteomic studies cannot.

PMID- 29050962
TI  - Han's model parameters for microalgae grown under intermittent illumination:
      Determined using particle swarm optimization.
AB  - This work provides a model and the associated set of parameters allowing for
      microalgae population growth computation under intermittent lightning. Han's
      model is coupled with a simple microalgae growth model to yield a relationship
      between illumination and population growth. The model parameters were obtained by
      fitting a dataset available in literature using Particle Swarm Optimization
      method. In their work, authors grew microalgae in excess of nutrients under
      flashing conditions. Light/dark cycles used for these experimentations are quite
      close to those found in photobioreactor, i.e. ranging from several seconds to one
      minute. In this work, in addition to producing the set of parameters, Particle
      Swarm Optimization robustness was assessed. To do so, two different swarm
      initialization techniques were used, i.e. uniform and random distribution
      throughout the search-space. Both yielded the same results. In addition, swarm
      distribution analysis reveals that the swarm converges to a unique minimum. Thus,
      the produced set of parameters can be trustfully used to link light intensity to
      population growth rate. Furthermore, the set is capable to describe photodamages
      effects on population growth. Hence, accounting for light overexposure effect on
      algal growth.

PMID- 29050963
TI  - Long-chain glucosylceramides crosstalk with LYN mediates endometrial cell
      migration.
AB  - Endometriosis is a disease characterized by regurgitated lesions which are
      invasive and migratory, embedding at ectopic, extra-uterine locations.
      Extracellular glucosylceramides (GlcCers), bioactive sphingolipids potentiating
      signals for cell migration, are found in elevated levels in endometriosis;
      however underlying mechanisms that result in cellular migration are poorly
      defined. Here, we demonstrated that internalized GlcCer induced migratory
      activity in immortalized human endometrial stromal cells (HESCs), with highest
      potency observed in long-chain GlcCer. Long-chain ceramide (Cer) similarly
      induced cellular migration and mass spectrometry results revealed that the
      migratory behavior was contributed through glycosylation of ceramides. Cells
      treated with GlcCer synthase inhibitor, or RNAi-mediated knockdown of
      glucosylceramide synthase (GCS), the enzyme catalyzing GlcCer production
      attenuated cell motility. Mechanistic studies showed that GlcCer acts through
      stromal cell-derived factor-1 alpha and its receptor, CXC chemokine receptor 4
      (SDF-1alpha-CXCR4) signaling axis and is dependent on phosphorylation of LYN
      kinase at Tyr396, and dephosphorylation of Tyr507. Migration was prominently
      attenuated in cells exposed to CXCR4 antagonist, AMD3100, yet can be rescued with
      diprotin A, which prevents the degradation of SDF-1alpha. Furthermore, blocking
      of LYN kinase activity in the presence of SDF-1alpha and GlcCer reduced HESC
      migration, suggesting that LYN acts downstream of GlcCer-SDF-1alpha-CXCR4 axis as
      part of its intracellular signal transduction. Our results reveal a novel role of
      long-chain GlcCer and the dialog between GlcCer, LYNpTyr396 and SDF-1alpha-CXCR4
      in inducing HESC migration. This finding may improve our understanding how
      endometriotic lesions invade to their ectopic sites, and the possibility of using
      GlcCer to modulate the SDF-1alpha-CXCR4-LYNpTyr396 axis in endometriosis.

PMID- 29050964
TI  - Surgical site infection following open reduction and internal fixation of a
      closed ankle fractures: A retrospective multicenter cohort study.
AB  - BACKGROUND: Identification of risk factors for surgical site infection (SSI)
      after surgical ankle fractures was important, but related evidence was
      inadequate. This study was conducted to investigate the incidence and risk
      factors for SSI after open reduction and internal fixation (ORIF) of a closed
      ankle fractures. METHODS: Patients who underwent ORIF for a closed ankle
      fractures at 3 centers between July 2015 and January 2017 were included.
      Electronic medical recordings (EMR) and Picture Archiving and Communication
      Systems (PACS) were inquired for information on patients' clinical and
      radiographic characteristics. The potential factors include 4 aspects:
      demographics, injury-related, surgery-related and biochemical indictors. Factors
      related with SSI were analyzed by univariate and further by multivariate logistic
      regression model. RESULTS: During the hospitalization, 3.7% (46/1247) of patients
      developed SSI, with 1.12% (14/1247) for deep and 2.57% (32/1247) for superficial
      SSI. Approximately half of SSIs were caused by Methicillin-resistant
      Staphylococcus aureus (MRSA). After adjustment for confounding factors, higher
      body mass index (BMI), surgeon level (residents or treating surgeon), surgical
      duration>130mins, delayed surgery, preoperative TP < 60 g/L were significant risk
      factor or predictors for SSI occurrence. CONCLUSIONS: After comprehensive
      evaluation of patients medical conditions, immediate operation by a surgeon with
      more expertise could effectively reduce SSI occurrence.

PMID- 29050965
TI  - The revised staging system for malignant pleural mesothelioma based on
      surveillance, epidemiology, and end results database.
AB  - BACKGROUND: Several staging systems for MPM have been introduced. However, none
      of them provide perfect survival stratification among heterogeneous patients. The
      aim of this population-based cohort study was to propose adjustments to current
      staging system for malignant pleural mesothelioma (MPM). METHODS: We retrieved
      MPM data from Surveillance, Epidemiology, and End Results database (1973-2014).
      Kaplan-Meier method was derived to examine the prognostic effects of tumor, lymph
      node, metastasis and histology features. Proportional hazards models guided
      adjustments to stage groupings. The accuracy of staging systems at predicting
      survival was evaluated by concordance index and bootstrap resampling. RESULTS: A
      total of 1110 MPM cases were extracted from SEER. T stage failed to demonstrate
      survival difference between adjacent categories with the exception of T3 versus
      T4 (P < 0.001). Patients in M0 had better prognosis than those in M1 (P < 0.001).
      Exploratory analyses suggested important survival difference for single-versus
      multiple-site M1 cases (P < 0.001), but not for different metastatic sites (P =
      0.286). Histology subtype was a significant prognostic indicator (P < 0.001).
      Regrouping of TNM and histology combinations resulted in the best concordance
      index (0.683), compared with UICC 2010 (0.578) and IASLC 2016 (0.585) staging
      systems. The revised staging system also improved patients distribution
      (IA:33.8%, IB:17.0%, II: 20.7%, IIIA:10.6%, IIIB: 6.8%, IV:11.1%). Log-rank
      analyses and calibration plots both demonstrated the new stage achieved optimal
      survival prediction and discrimination. CONCLUSION: The revised staging system
      improved patients distribution and survival stratification for MPM.

PMID- 29050966
TI  - Characterization of gamma-tubulin filaments in mammalian cells.
AB  - Overexpression of gamma-tubulin leads to the formation of filaments, but nothing
      is known about such filaments with regard to possible presence in cells,
      structure and probable dynamics. Here, we used mammalian cell lines to
      investigate the ability of gamma-tubulin to form filaments. We found that gamma
      tubulin produces fibers called gamma-tubules in a GTP-dependent manner and that
      gamma-tubules are made up of pericentrin and the gamma-tubulin complex proteins
      2, 3, 5 and 6. Furthermore, we noted that the number of cells with cytosolic
      gamma-tubules is increased in non-dividing cells. Our experiments showed that
      gamma-tubules are polar structures that have a low regrowth rate compared to
      microtubules. Also, we observed that gamma-tubules were disassembled by treatment
      with cold, colcemid, citral dimethyl acetal, dimethyl fumarate or mutation of
      gamma-tubulin GTPase domain, but were increased in number by treatment with taxol
      or by stable expression of the gamma-tubulin1-333 GTPase domain. Our results
      demonstrate that gamma-tubulin forms filaments, and such assembly is facilitated
      by the GTPase domain of gamma-tubulin.

PMID- 29050967
TI  - Role of K+ channels in regulating spontaneous activity in the muscularis mucosae
      of guinea pig bladder.
AB  - To explore the roles of various K+ channels in regulating the spontaneous
      activity of bladder muscularis mucosae (MM) that is considered to play an
      important role in maintaining mucosal function. Effects of K+ channel modulators
      on electrical and contractile activity in the guinea-pig bladder MM were examined
      using intracellular microelectrode and isometric tension recording. The MM
      predominately generated bursting spontaneous action potentials (SAPs) and phasic
      contractions (SPCs) that were blocked by nifedipine (1uM). NS309 (10uM), a small
      conductance Ca2+-activated K+ (SK) channel opener, dramatically prolonged after
      hyperpolarisation (AHP) and converted bursting SAPs into individually action
      potentials in an apamin (100nM)-sensitive manner. Apamin alone increased the
      number of SAPs during bursts. NS1619 (10uM), a large-conductance Ca2+-activated
      K+ (BK) channel opener, abolished SAPs in a manner reversed by iberiotoxin (IbTX,
      100nM), a BK channel blocker. IbTX alone enlarged SAPs and abolished their AHPs.
      Flupirtine (10uM), a voltage-dependent K+ channel (Kv7) opener, diminished SAPs
      in a manner reversed by XE991 (10uM), a Kv7 channel blocker. XE991 alone exerted
      modest excitatory effects on SAPs. These K+ channel modulators had corresponding
      effects on SPCs. Bursting SAP firing appears to result from a lower level
      activation of SK channels in MM than that DSM. BK channels play a predominant
      role in regulating SAP configuration, while Kv7 channels have only a marginal
      role. The prevention of bursting SAPs and associated reduction in SPCs upon the
      pharmacological activation of a reserved population of SK channels may well have
      a considerable therapeutic potential.

PMID- 29050968
TI  - Discovery and electrophysiological characterization of SKF-32802: A novel hERG
      agonist found through a large-scale structural similarity search.
AB  - Despite the importance of the hERG channel in drug discovery and the sizable
      number of antagonist molecules discovered, only a few hERG agonists have been
      discovered. Here we report a novel hERG agonist; SKF-32802 and a structural
      analog of the agonist NS3623, SB-335573. These were discovered through a
      similarity search of published hERG agonists. SKF-32802 incorporates an amide
      linker rather than NS3623's urea, resulting in a compound with a different
      mechanism of action. We find that both compounds decrease the time constant of
      open channel kinetics, increase the amplitude of the envelope of tails assay,
      mildly increased the amplitude of the IV curve, bind the hERG channel in either
      open or closed states, increase the plateau of the voltage dependence of
      activation and modulate the effects of the hERG antagonist, quinidine. Neither
      compound affects inactivation nor deactivation kinetics, a property unique among
      hERG agonists. Additionally, SKF-32802 induces a leftward shift in the voltage
      dependence of activation. Our structural models show that both compounds make
      strong bridging interactions with multiple channel subunits and are stabilized by
      internal hydrogen bonding similar to NS3623, PD-307243 and RPR26024. While SB
      335573 binds in a nearly identical fashion as NS3623, SKF-32802 makes an
      additional hydrogen bond with neighboring threonine 623. In summary, SB-335573 is
      a type 4 agonist which increases open channel probability while SKF-32802 is a
      type 3 agonist which induces a leftward shift in the voltage dependence of
      activation.

PMID- 29050970
TI  - Polyphenolic profile and biological activities of black carrot crude extract
      (Daucus carota L. ssp. sativus var. atrorubens Alef.).
AB  - Black carrot (Daucus carota L. ssp. sativus var. atrorubens Alef.) is a valuable
      source of carbohydrates, minerals and vitamins and contains also high amounts of
      anthocyanins giving the characteristic deep-purple color. These latter compounds
      are known as natural dyes used in the food and pharmaceutical industry that have
      recently attracted much attention for their healthful properties. The aim of this
      work was to investigate for the first time the polyphenolic profile and
      biological properties of a black carrot crude extract (BCCE) through an in-depth
      analysis of the main polyphenolic classes evaluating its antioxidant,
      cytoprotective and anti-angiogenic properties. Twenty five polyphenols were
      quantified by LC-DAD-FLD-MS/MS analysis (anthocyanins 78.06%, phenolic acids
      17.89% and other flavonoids 4.06%) with polyglycosylated cyanidins as major
      components. In addition, BCCE showed a strong antioxidant and free radical
      scavenging activity particularly in the hydrogen transfer-based assays (ORAC and
      beta-carotene bleaching) and a significant increase in the cell viability.
      Furthermore, BCCE exhibited a strong anti-angiogenic activity at the highest
      concentration assayed on the chick chorioallantoic membrane (50MUg/egg). In
      conclusion, the obtained results demonstrated the antioxidant, cytoprotective and
      anti-angiogenic properties of BCCE, which highlight that the higher biological
      activity of BCCE is probably due to the synergic effects exerted by various
      polyphenolic classes.

PMID- 29050969
TI  - A novel selective MAO-B inhibitor with neuroprotective and anti-Parkinsonian
      properties.
AB  - We previously reported that 1,3-bisbenzylimidazolium (DBZIM) bromide was
      neuroprotective for the dopaminergic system in Parkinson's disease (PD) models of
      rodent, however the underlying mechanism was unclear. We currently further
      confirmed that DBZIM ameliorated the Parkinsonian motor deficit and protected the
      nigrostriatal tract from the neurotoxicity of 1-methyl-4-(2'-methylphenyl)
      1,2,3,6-tetrahydropyridine (2'-CH3-MPTP) in C57Bl/6 mice. The dopaminergic
      degeneration in the substantia nigra par compacta (SNc) and striatum was analyzed
      by immunohistochemistry while the monoamine oxidase B (MAO-B) inhibition effect
      of DBZIM was determined by enzyme kinetics. DBZIM was at least as effective as
      the clinically approved anti-PD drug, l-deprenyl (Selegiline), for both
      neuroprotection and correction of motor deficits. Mechanistically, DBZIM
      inhibited the specific activity of MAO-B in the striatum and C6 cells without
      affecting the protein expression. DBZIM directly inhibited the enzymatic activity
      of a purified MAO-B protein with an estimated Ki value from 780 to 940nM, in par
      with that of l-deprenyl (970nM). The physical interaction between DBZIM and MAO-B
      was proven by NMR analysis, with Kd around 21.5-46.8MUM. Our binding and
      modelling data further illustrated that DBZIM is a mixed inhibitor with its
      binding to active site partially hindering the substrate binding. Therefore,
      inhibiting MAO-B is a major mechanism through which DBZIM confers neuroprotection
      for the dopaminergic neurons against 2'-CH3-MPTP toxicity. Remarkably, the post
      lesion treatment with DBZIM provided greater anti-parkinsonian and
      neuroprotective effects than the l-deprenyl. The current study, together with our
      previous findings in a 6-OHDA PD model, demonstrated that DBZIM is a promising
      neuroprotectant for PD with anti-MAO-B property.

PMID- 29050971
TI  - A simple method for obtaining rice black-streaked dwarf virus-infected small
      brown planthopper nymphs.
AB  - Rice black-streaked dwarf virus (RBSDV), an important rice virus, is transmitted
      by vector small brown planthopper (SBPH) in a persistent manner, but not
      transovarial transmission. In order to obtain viruliferous SBPH nymphs for
      relevant research, a simple and reliable method was developed, through allowing
      SBPH adults laying eggs on RBSDV-infected rice plants. The results showed the
      hatching nymphs on diseased plants could early acquire virus, and the virus was
      detected in 2nd-instar nymphs from the spawning method, which was earlier than
      insect feed on diseased plant. The average viruliferous rate of SBPH from the
      spawning method was 32.9%, which was not lower than the feeding diseased plant
      method. The novel method was very easy to operate and time-saving, facilitating
      the study on the interaction between RBSDV and SBPH nymphs (especially young 2nd
      4th instar nymphs), such as, the effect of RBSDV on nymph development, host plant
      orientation preference of viruliferous nymph, identification of viral interacting
      protein in nymph, etc.

PMID- 29050972
TI  - LAIR-1 limits neutrophil extracellular trap formation in viral bronchiolitis.

PMID- 29050973
TI  - A simulation model for methane emissions from landfills with interaction of
      vegetation and cover soil.
AB  - Global climate change and ecological problems brought about by greenhouse gas
      effect have become a severe threat to humanity in the 21st century. Vegetation
      plays an important role in methane (CH4) transport, oxidation and emissions from
      municipal solid waste (MSW) landfills as it modifies the physical and chemical
      properties of the cover soil, and transports CH4 to the atmosphere directly via
      their conduits, which are mainly aerenchymatous structures. In this study, a
      novel 2-D simulation CH4 emission model was established, based on an interactive
      mechanism of cover soil and vegetation, to model CH4 transport, oxidation and
      emissions in landfill cover soil. Results of the simulation model showed that the
      distribution of CH4 concentration and emission fluxes displayed a significant
      difference between vegetated and non-vegetated areas. CH4 emission flux was 1-2
      orders of magnitude higher than bare areas in simulation conditions. Vegetation
      play a negative role in CH4 emissions from landfill cover soil due to the strong
      CH4 transport capacity even though vegetation also promotes CH4 oxidation via
      changing properties of cover soil and emitting O2 via root system. The model will
      be proposed to allow decision makers to reconsider the actual CH4 emission from
      vegetated and non-vegetated covered landfills.

PMID- 29050974
TI  - Liquefaction of ground tire rubber at low temperature.
AB  - Low-temperature liquefaction has been investigated as a novel method for
      recycling ground tire rubber (GTR) into liquid using an environmentally benign
      process. The liquefaction was carried out at different temperatures (140, 160 and
      180  degrees C) over variable time ranges (2-24 h) by blending the GTR with
      aromatic oil in a range from 0 to 100 parts per hundred rubber (phr). The
      liquefied GTR was separated into sol (the soluble fraction of rubber which can be
      extracted with toluene) and gel fractions (the solid fraction obtained after
      extraction) to evaluate the reclaiming efficiency. It was discovered that the
      percentage of the sol fraction increased with time, swelling ratio and
      temperature. Liquefied rubber was obtained with a high sol fraction (68.34 wt%)
      at 140  degrees C. Simultaneously, separation of nano-sized carbon black from the
      rubber networks occurred. The separation of carbon black from the network is the
      result of significant damage to the cross-linked-network that occurs throughout
      the liquefaction process. During liquefaction, a competitive reaction between
      main chain scission and cross-link bond breakage takes place.

PMID- 29050975
TI  - Disaster waste management in Italy: Analysis of recent case studies.
AB  - The geomorphology of the Italian territory causes the incidence of many disasters
      like earthquakes and floods, with the consequent production of large volumes of
      waste. The management of such huge flows, produced in a very short time, may have
      a high impact on the whole emergency response. Moreover, historical data related
      to disaster waste management are often not easily accessible; on the other hand,
      the availability of data concerning previous events could support the emergency
      managers, that have to take a decision in a very short time. In this context, the
      present paper analyses four relevant recent case studies in Italy, dealing with
      disaster waste management after geologic and hydrologic natural events.
      Significant differences have been observed in the quantity and types of generated
      wastes, and, also, in the management approach. Such differences are mainly
      associated with the kind of disaster (i.e. earthquake vs. flood), to the
      geographical location (i.e. internal vs. coastal area), to the urbanisation level
      (i.e. industrial vs. urban). The study allowed the identification of both
      strengths and weaknesses of the applied waste management strategies, that
      represent "lessons to learn" for future scenarios. Even though it deals with
      Italian case studies, this manuscript may have a high impact also at
      international level, making available for the first-time emergency waste
      management data, that are considered an indispensable support for decision
      makers.

PMID- 29050976
TI  - Evolution in situ of ARI-A in pB2-1, a type 1 IncC plasmid recovered from
      Klebsiella pneumoniae, and stability of Tn4352B.
AB  - The IncC plasmid pB2-1, from a Klebsiella pneumoniae isolate recovered in
      Brisbane prior to 1995, belongs to a subtype of type 1 IncC plasmids, here
      designated type 1a, that includes those carrying carbapenem resistance genes such
      as blaNDM and blaKPC. pB2-1 carries a 2358bp deletion in the rhs1 gene found in
      four other type 1a IncC plasmids. pB2-1 confers resistance to ampicillin,
      gentamicin, kanamycin, neomycin, tobramycin, sulfamethoxazole, tetracycline and
      trimethoprim. It transferred at a frequency of 4.7*10-3 transconjugants per
      donor, similar to that of another type 1a plasmid pDGO100 but ten-fold lower than
      for its closest relative pRMH760. This difference may be due to a single amino
      acid substitution in TraL. pB2-1 has an ISEc52 insertion in the dsbC gene,
      demonstrating that dsbC is not essential for transfer. pB2-1 lacks the ARI-B
      insertion and hence the sul2 gene. The resistance genes sul1, dfrA10, aphA1a,
      blaTEM, aadB, and tetA(B) are all in the ARI-A island, in a configuration that
      has evolved from ARI-A of pRMH760 in two steps. A 10.3kb segment extending from
      the catA1 gene to the end of pDUmer module was lost via homologous recombination
      between two copies of IS4321. In addition, a 5.3kb segment extending from IS1326
      to the left end of Tn4352B was replaced with an 18.7kb tet(B)-containing segment
      bounded on one end by IS1 and on the other by IS26. The IS26-bounded transposon
      Tn4352B was shown to be stable in K. pneumoniae in contrast to the high
      instability observed in E. coli.

PMID- 29050977
TI  - Prophylactic role of taurine and its derivatives against diabetes mellitus and
      its related complications.
AB  - Taurine is a conditionally essential amino acid present in the body in free form.
      Mammalian taurine is synthesized in the pancreas via the cysteine sulfinic acid
      pathway. Anti-oxidation and anti-inflammation are two main properties through
      which it exerts its therapeutic effects. Many studies have shown its excellent
      therapeutic potential against diabetes mellitus and related complications like
      diabetic neuropathy, retinopathy, nephropathy, hematological dysfunctions,
      reproductive dysfunctions, liver and pancreas related complications etc. Not only
      taurine, a number of its derivatives have also been reported to be important in
      ameliorating diabetic complications. The present review has been aimed to
      describe the importance of taurine and its derivatives against diabetic metabolic
      syndrome and related complications.

PMID- 29050978
TI  - Chrysin attenuates atopic dermatitis by suppressing inflammation of
      keratinocytes.
AB  - We previously reported the inhibitory effect of chrysin, a natural flavonoid
      plentifully contained in propolis, vegetables and fruits, on the mast cell
      mediated allergic reaction. In this study, we evaluated the effect of chrysin on
      atopic dermatitis (AD) and defined underlying mechanisms of action. We used an AD
      model in BALB/c mice by the repeated local exposure of 2,4-dinitrochlorobenzene
      (DNCB) and house dust mite (Dermatophagoides farinae extract, DFE) to the ears.
      Repeated alternative treatment of DNCB/DFE caused AD-like skin lesions. Oral
      administration of chrysin diminished AD symptoms such as ear thickness and
      histopathological analysis, in addition to serum IgE and IgG2a levels. Chrysin
      decreased infiltration of mast cells, and reduced serum histamine level. Chrysin
      also suppressed AD by inhibiting the inflammatory responses of Th1, Th2, and Th17
      cells in mouse lymph node and ear. Interestingly, chrysin significantly inhibited
      the production of cytokines, Th2 chemokines, CCL17 and CCL22 by the down
      regulation of p38 MAPK, NF-kappaB, and STAT1 in tumor necrosis factor (TNF)
      alpha/interferon (IFN)-gamma-stimulated human keratinocytes (HaCaT). Chrysin also
      inhibited TNF-alpha/IFN-gamma-stimulated IL-33 expression in HaCaT cells and
      mouse primary keratinocytes. Taken together, the results indicate that chrysin
      suppressed AD symptoms, suggesting that chrysin might be a candidate for the
      treatment of AD and skin allergic diseases.

PMID- 29050979
TI  - Comparison of 3 risk estimators to guide initiation of statin therapy for primary
      prevention of cardiovascular disease.
AB  - BACKGROUND: Among high-risk individuals, statins are beneficial for primary
      prevention of cardiovascular disease (CVD). In Nigeria, currently, there are no
      CVD prevention guidelines, so the use of CVD risk estimation to guide statin
      therapy is left to the discretion of the physician. OBJECTIVE: The objective of
      the study was to compare 3 CVD risk estimation tools in the evaluation of
      patients presenting to a tertiary hospital in Nigeria. METHODS: Cross-sectional
      study involving 295 patients with any CVD risk factors but not taking statins.
      Traditional CVD risk factors were assessed with a standard questionnaire and
      laboratory evaluation. Ten-year CVD risk was estimated with American College of
      Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease
      (ACC/AHA ASCVD) Risk Estimator (2013), Framingham Risk Score (Framingham Risk
      Score [FRS] 2008), and the World Health Organisation/International Society of
      Hypertension (WHO/ISH) risk prediction chart for Africa Region D. Kappa statistic
      was used to determine agreement among the estimators. RESULTS: The mean age was
      48.4 +/- 10.4 years; 60.7% were females. Risk factors for CVD were hypertension
      (56.3%), dyslipidemia (41.4%), diabetes (20%), obesity (28.5%), and cigarette
      smoking (4.4%). In all, 50.2%, 16.9%, and 15.2% were classified as high risk
      using the ACC/AHA ASCVD Risk Estimator, FRS 2008, and WHO/ISH risk chart,
      respectively. The agreement was moderate between FRS and WHO/ISH (Kappa 0.414, P
      < .001) and fair between ACC/AHA Estimator and WHO/ISH (Kappa 0.223, P < .001)
      and between ACC/AHA Estimator and FRS (Kappa 0.301, P < .001). CONCLUSIONS: The
      considerable variation in prediction of high risk using the 3 tools may lead to
      underutilization of evidence-based therapy. This underscores the dire need for
      the development of risk prediction tools derived from our own Nigerian
      population.

PMID- 29050980
TI  - Association of low-density lipoprotein pattern with mortality after myocardial
      infarction: Insights from the TRIUMPH study.
AB  - BACKGROUND: Studies of incident coronary heart disease risk within low-density
      lipoprotein (LDL) subclass (small, dense vs large, buoyant) have shown mixed
      results. No prospective cohort study has examined the association of small,
      dense, or large, buoyant LDL with mortality after myocardial infarction (MI).
      OBJECTIVE: The objective of the study was to examine association of LDL pattern
      after MI and death. METHODS: In 2476 patients hospitalized for MI, LDL pattern (A
      [large, buoyant], A/B [mixed], and B [small, dense]) was established by
      ultracentrifugation using Vertical Auto Profile. Using time-to-event analysis, we
      examined the association with 5-year mortality within LDL patterns, after
      adjusting for important patient and treatment characteristics. We additionally
      adjusted for LDL cholesterol (LDL-C) and triglyceride levels and used directly
      measured LDL-C and non-high-density lipoprotein cholesterol as exposures.
      RESULTS: Patterns A, A/B, and B were present in 39%, 28%, and 33% of patients,
      respectively, with incident rates (per 1000 patient-years) of 50, 34, and 24 for
      all-cause and 24, 19, and 10 for CV mortality. The hazard ratios (95% confidence
      interval) with LDL patterns A/B and B compared with pattern A were 0.77 (0.61,
      0.99) and 0.67 (0.51, 0.88) for all-cause, 0.94 (0.67, 1.33) and 0.69 (0.46,
      1.03) for cardiovascular, and 0.64 (0.45, 0.91) and 0.65 (0.45, 0.93) for
      noncardiovascular mortalities, respectively. Results were similar when further
      adjusted for LDL-C and triglycerides, or with LDL-C and non-high-density
      lipoprotein cholesterol as exposures. CONCLUSION: Compared with LDL pattern A,
      pattern B was significantly associated with reduced all-cause and non-CV
      mortalities with a trend for lower CV mortality after MI, independent of LDL-C
      and triglycerides.

PMID- 29050981
TI  - Evolutional change in epicardial fat and its correlation with myocardial diffuse
      fibrosis in heart failure patients.
AB  - OBJECTIVES: The aim of this study was to characterize the characteristics of
      epicardial fat (EAT) in different stage heart failure (HF) patients and its
      relationship between cardiac fibrosis. BACKGROUND: EAT is visceral adipose tissue
      that possesses inflammatory properties. Inflammation and obesity are associated
      with cardiac fibrosis, but the relationship between cardiac fibrosis and EAT is
      unknown. METHODS: EAT volume was measured using cardiac magnetic resonance
      imaging (CMR) in 180 subjects: 58 patients with systolic HF, 63 patients with HF
      and preserved ejection fraction, and 59 patients without HF. CMR derived
      myocardial extracellular volume (ECV) was used for fibrosis quantification.
      RESULTS: Patients with systolic HF had significantly more EAT compared with
      patients with HF and preserved ejection fraction or the control group (patients
      without HF) (indexed EAT volume [mL/m2], 27.0 [22.7-31.6] vs 25.6 [21.4-31.2] and
      24.2 [21.0-27.6], P < .05). The adjusted EAT amount was associated with ECV
      completely independent of age, hypertension, diabetes, etiology of HF, left
      ventricular ejection fraction, CMR-late gadolinium enhancement (LGE), left
      ventricular mass index, and left ventricular end-diastolic volume index
      (correlation coefficient: 0.49; 95% confidence interval: 0.12-0.86, P < .01).
      Increased CMR ECV was more associated with EAT in those with advanced age, male
      sex, LGE on magnetic resonance imaging-LGE images, and less left ventricular end
      diastolic volume index. CONCLUSIONS: EAT volume is highly associated with CMR ECV
      independent of traditional risk factors and left ventricular mass or volume.
      Whether EAT plays a role in the long-term prognosis of HF requires future
      investigation.

PMID- 29050982
TI  - Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and
      metastasis and overcomes cisplatin resistance.
AB  - Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP)
      is widely used as the standard GC treatment, but relapse and metastasis are
      common because of intrinsic or acquired drug resistance. The mitogen-activated
      protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK)
      pathway contributes to GC progression and drug resistance, but targeting the MAPK
      ERK pathway is challenging in GC therapy. Here, we demonstrated that dual
      specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor
      overall survival and progression-free survival. Knockdown DUSP6 inhibited GC
      proliferation, migration, invasion and induced apoptosis. (E/Z)-BCI hydrochloride
      (BCI), a DUSP6 small molecule inhibitor, increased the activity of ERK but
      interestingly decreased the expression of ERK response genes in BGC823, SGC7901
      and CDDP-resistant SGC7901/DDP cells. BCI also caused cell death through the DNA
      damage response (DDR) pathway. Moreover, BCI inhibited cell proliferation,
      migration and invasion in a receptor-independent manner and enhanced CDDP
      cytotoxicity at pharmacological concentrations in the GC cells. In vivo
      experiments further showed that BCI enhances the antitumor effects of CDDP in
      cell-based xenografts and PDX models. In summary, our findings indicated that
      disruption of DUSP6 by BCI enhanced CDDP-induced cell death and apoptosis in GC
      may partly through ERK and DDR pathways. Thus, this study suggests that DUSP6 is
      a potential prognostic biomarker and a promising target for GC therapy.

PMID- 29050983
TI  - Precision diagnosis and treatment of liver cancer in China.
AB  - Liver cancer ranks the sixth in cancer incidence and the second in tumor related
      mortality worldwide, with over half of the new cases and deaths occur in China.
      Because of difficulties in early diagnosis, rapid progression and lack of
      targeted drugs, the survival rate of liver cancer is extremely low. The existence
      of extraordinary heterogeneity has greatly limited the progress in early
      detection, molecular classification and targeted therapy of live cancer, owing to
      its varied risk factors, genetic susceptibilities, morphological diversity and
      microenvironmental discrepancies. Based on the heterogeneity of individual
      patients, precision medicine brings a new dimension to cancer personalized
      diagnosis and more-targeted treatment, and even give us access to pre-clinical
      screening of tumors in high risk populations. The present review article will
      provide progresses in precision diagnosis, molecular classification, signaling
      disregulation, preclinical models and personalized treatment of liver cancer in
      China.

PMID- 29050984
TI  - Expression, purification and characterization of a novel double-sites mutant of
      the single-chain sweet-tasting protein monellin (MNEI) with both improved
      sweetness and stability.
AB  - The sweet protein monellin has high sweet potency with limited stability. In this
      study, 3 double-sites mutants (E2N/E23A, E2N/Y65R and E23A/Y65R) of the single
      chain monellin (MNEI) were constructed. The proteins were expressed in E. coli
      BL21 and purified to homogeneity by nickel affinity chromatography with yields
      above 10 mg/L cell culture. Introduction of a sweeter mutant E2N into E23A or
      Y65R (E2N/E23A and E2N/Y65R) led to about 3-fold increase of sweetness, while
      addition of a more stable mutant E23A into E2N or Y65R (E2N/E23A and E23A/Y65R)
      resulted in improved thermal stability (about 10  degrees C). The results
      indicate that residues E2 and E23 mediate the sweetness and thermal stability of
      the protein, respectively. Multiple mutations of different residues (E2N/E23A)
      led to an additive performance with both improved sweetness and stability,
      suggesting that the sweetness and stability could be modulated by the independent
      molecular mechanism. The sweeter and thermal stable variant has a potential in
      further industrial applications.

PMID- 29050986
TI  - Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF
      inhibitor NSC23766 has off target effects on CXCR4.
AB  - Cell migration towards a chemotactic stimulus relies on the re-arrangement of the
      cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and
      Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst
      other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis
      but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4,
      breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and
      Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling
      does not regulate cell migration in either suspension or adherent cells. We have
      confirmed the involvement of Rac1 with the use of a specific Rac1 blocking
      peptide. We also used a Rac1 inhibitor EHT 1864 and a Rac1-GEF inhibitor NSC23766
      to probe the importance of Rac1 in chemotaxis. Both inhibitors did not block CCL3
      induced chemotaxis, but they were able to block CXCL12-induced chemotaxis. This
      confirms that Rac1 activation is not essential for CCL3-induced migration,
      however NSC23766 might have secondary effects on CXCR4. This small molecule
      exhibits agonistic features in internalisation and cAMP assays, whereas it acts
      as an antagonist for CXCR4 in migration and calcium release assays. Our findings
      strongly suggest that Rac1 activation is not necessary for CCL3 signalling, and
      reveal that NSC23766 could be a novel CXCR4 receptor ligand.

PMID- 29050985
TI  - Bromodomain protein BRD4 promotes cell proliferation in skin squamous cell
      carcinoma.
AB  - The present study examined the expression and biological functions of bromodomain
      containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our
      results show that BRD4 mRNA and protein expression was upregulated in human skin
      SCC cells, as compared to its level in the normal skin keratinocytes and
      fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in
      proliferation inhibition, apoptosis and cell cycle arrest in both established
      (A431 cell line) and primary skin SCC cells. Furthermore, BRD4 knockdown (by
      targeted shRNAs) or knockout (by CRISPR/Cas9) largely inhibited A431 cell
      proliferation. Reversely, forced-overexpression of BRD4 in A431 cells facilitated
      cell proliferation. We show that BRD4 is required for the expression of several
      oncogenes, including cyclin D1, Bcl-2 and MYC. BRD4 inhibition, knockdown or
      knockout significantly decreased above oncogene expression in SCC cells. In vivo,
      CRISPR/Cas9-mediated BRD4 knockout significantly suppressed A431 xenograft tumor
      growth in severe combined immunodeficient (SCID) mice. Together, our results
      suggest that BRD4 could be a novel and pivotal oncogenic protein of skin SCC.

PMID- 29050987
TI  - Gill transcriptomes reveal involvement of cytoskeleton remodeling and immune
      defense in ammonia stress response in the banana shrimp Fenneropenaeus
      merguiensis.
AB  - The banana shrimp, Fenneropenaeus merguiensis, is an important fishery species in
      the Indo-West Pacific region. As the shrimp is very sensitive to stressors such
      as ammonia stress in water, understanding the molecular mechanisms of stress
      tolerance in F. merguiensis is of pivotal importance for improving its farming
      performance. In the current study, by using the RNA sequencing platform and
      comparative transcriptomic analysis, we conducted a comprehensive study on the
      transcriptomic changes of F. merguiensis in response to ammonia stress. A total
      of 106,996 unique transcripts (or unigenes) with an average length of 672 bp and
      a N50 value of 1164 bp were recovered, and a large number of potential SSR loci
      in the transcriptome were identified. Totally, 55,529 transcripts can find
      significant hits when compared to known sequences in major databases including
      the nr, nt, SWISSPROT, GO, COG, and KEGG databases. Analysis of differential gene
      expression between the ammonia-challenged group and the control group revealed
      that 9190 annotated transcripts were differentially expressed upon ammonia
      exposure. Among them, 3712 were significantly induced while 5478 of them were
      repressed. Functional enrichment analysis of these differentially expressed genes
      further showed that 22 Gene Ontology terms and 62 KEGG pathways were
      significantly over-represented. Remarkably, many of the genes showing the largest
      magnitude of expression changes were related to cytoskeleton remodeling and
      immune response, highlighting the involvement of these biological processes in
      the ammonia stress response of F. merguiensis. Our study is the first
      comprehensive investigation on the transcriptomic response to ammonia stress in
      F. merguiensis. The genes and pathways identified here not only represent
      valuable genetic resources for development of molecular markers and genetic
      breeding studies, but open new avenues for studies on the molecular mechanisms of
      ammonia stress tolerance in penaeid shrimp.

PMID- 29050988
TI  - Physiological and immune response of juvenile rainbow trout to dietary bovine
      lactoferrin.
AB  - Lactoferrin, a large multifunctional glycoprotein, is involved in many
      physiological functions but its immunomodulatory pathways are not well
      characterized in fish. The objective of the present study was to investigate the
      temporal effect of dietary bovine lactoferrin (BLf) at low (0.1%) and high (1%)
      on immunological organs of rainbow trout juveniles. BLf diets did not affect
      specific growth rate, haematocrit, splenic index, spleen respiratory burst
      activity as well as humoral (mIgM) and neutrophils (MPO) gene expressions after
      short term - 35 days (D35) and long term nutrient test - 51 days (D51) of
      feeding. Both low and high BLf doses induced enhanced level of plasma alternative
      complement activity, plasma total immunoglobulin on D35 and D51, lymphocyte plus
      thrombocyte cell proportion on D35 and monocyte cell proportion in total blood
      leukocyte cells on D51. On D51 but not on D35, BLf diets upregulated the
      expression of inflammatory genes in kidney for il-1 at the low BLf dose, il-8 at
      both BLf doses and il-6 at the high BLf dose in spleen, and il-10 at both BLf
      doses in kidney. Moreover, the expression of T helper (cd4-2alpha; cd4-2beta)
      genes was significantly upregulated only on D51 by both BLf doses in both spleen
      and kidney tissues. On D51, controls and BLf treated fish were intraperitoneally
      injected with A. salmonicida achromogenes. The expression of 13 immune genes was
      evaluated at 44 h post-injection (D54). The expression of lysozyme gene was
      upregulated by both BLf doses after bacterial infection both in spleen and
      kidney. The expression of mcsfralpha (spleen) and tgf-beta1 (kidney) was also
      modulated by both BLf doses. Low and high BLf doses enhanced disease resistance
      of rainbow trout juveniles with the cumulative survival rate of 36% and 38%
      respectively while those of the control was 19% after 14 days challenged with
      bacteria. The results indicate that BLf diets activated the humoral immunity,
      associated to blood leukocyte cells of rainbow trout after short term BLf
      administration, and the long term BLf administration was necessary for
      sensitizing other lymphoid organs such as in spleen and kidney. Only after long
      term test, BLf diets induced significantly higher levels of innate and adaptive
      immune gene expressions than those of the control. Dietary BLf activated more
      markedly the expression of innate immune genes than the adaptive ones; this
      upregulation of some immune genes could explain the high disease resistance
      observed in rainbow trout juveniles fed BLf.

PMID- 29050989
TI  - Feed Your Friends: Do Plant Exudates Shape the Root Microbiome?
AB  - Plant health in natural environments depends on interactions with complex and
      dynamic communities comprising macro- and microorganisms. While many studies have
      provided insights into the composition of rhizosphere microbiomes (rhizobiomes),
      little is known about whether plants shape their rhizobiomes. Here, we discuss
      physiological factors of plants that may govern plant-microbe interactions,
      focusing on root physiology and the role of root exudates. Given that only a few
      plant transport proteins are known to be involved in root metabolite export, we
      suggest novel families putatively involved in this process. Finally, building off
      of the features discussed in this review, and in analogy to well-known symbioses,
      we elaborate on a possible sequence of events governing rhizobiome assembly.

PMID- 29050990
TI  - Application of nucleic acid aptamers for detection of Apple stem pitting virus
      isolates.
AB  - DNA aptamers (PSA-H and MT32) were applied for the detection of Apple stem
      pitting virus (ASPV) isolates using an Enzyme-Linked Oligonucleotide Assay
      (ELONA) and Western blot analysis. The specificity and effectiveness of aptamers
      were verified in comparison to a conventional Enzyme Linked Immunosorbent Assay
      (ELISA). A genetically diverse group of ASPV isolates was tested. The results
      showed that aptamer MT32 detected a wider range of ASPV isolates than an aptamer
      PSA-H and proved to be superior to commercially available monoclonal antibodies.
      Aptamer MT32 produced higher signal intensity in ELONA with a virus-infected
      plant extracts than antibodies in ELISA. Moreover, the ELISA method failed to
      detect ASPV in six samples. The results presented in this study indicated that
      aptamer MT32 can be used as a receptor molecule of various immunoassay protocols
      for ASPV detection.

PMID- 29050991
TI  - Efficacy and Safety of Mycophenolate Mofetil in Patients With Autoimmune
      Hepatitis and Suboptimal Outcomes After Standard Therapy.
AB  - BACKGROUND & AIMS: Little is known about outcomes of patients with autoimmune
      hepatitis (AIH) who have a suboptimal outcome to standard therapy and are then
      given mycophenolate mofetil as rescue therapy. We evaluated the efficacy and
      safety of mycophenolate mofetil in patients failed by or intolerant to
      corticosteroids, with or without azathioprine. METHODS: We performed a
      retrospective study of 105 patients with AIH who received mycophenolate mofetil
      therapy after an inadequate response or intolerance to standard therapy (98%
      received combination therapy with corticosteroids plus thiopurines). Patients
      were recruited from 17 liver clinics via the Australian Liver Association
      Clinical Research Network. We reviewed records for baseline demographic features
      and characteristics of liver disease, initial therapy, mycophenolate mofetil
      indications, treatment outcome, and side effects. The primary outcome was
      biochemical remission, defined as levels of alanine and aspartate transferase and
      IgG level within the normal reference range, with or without normal liver
      histology within the first 2 years of treatment. RESULTS: The indication for
      mycophenolate mofetil therapy was non-response to treatment for 40% of cases and
      intolerance to therapy for 60%. Overall, 63 patients (60%) achieved biochemical
      remission following a median 12 weeks treatment with mycophenolate mofetil. The
      proportion of patients who achieved biochemical remission was similar between
      patients receiving mycophenolate mofetil for non-response to standard therapy
      (57%) and patients with intolerance to standard therapy (62%). However, a lower
      proportion of patients with cirrhosis achieved biochemical remission (47%) than
      patients without cirrhosis (6%) (P = .07). Serious adverse events occurred in 3
      patients (2.7%) including 1 death, and 10 patients (9.2%) discontinued
      mycophenolate mofetil because of adverse events. CONCLUSION: In this
      retrospective study of patients with AIH who received mycophenolate mofetil as a
      rescue therapy, we found the drug to be well tolerated and moderately effective,
      inducing biochemical remission in 60% of subjects. Rates of response are lower
      and rates of infection are higher in patients with AIH and cirrhosis. Prospective
      studies of mycophenolate mofetil are warranted for this population.

PMID- 29050992
TI  - The impact of 13-valent pneumococcal conjugate vaccination on virus-associated
      community-acquired pneumonia in elderly: Exploratory analysis of the CAPiTA
      trial.
AB  - OBJECTIVES: Our objective was to evaluate whether vaccination with the 13-valent
      pneumococcal conjugate vaccine (PCV13) prevents the incidence of community
      acquired pneumonia (CAP) caused by influenza (influenza-associated CAP, IA-CAP)
      or other respiratory viruses in the elderly. METHODS: This analysis was part of
      the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double
      blind, randomized, placebo-controlled trial in 84 496 immunocompetent individuals
      aged >=65 years. CAP was defined by clinical and radiological criteria, and
      oropharyngeal swabs were collected from all individuals referred to a sentinel
      centre with a clinical suspicion of pneumonia. Presence of influenza A and B,
      parainfluenza 1, 2, 3 and 4, human adeno-, boca-, corona-, metapneumo-, rhino-
      and respiratory syncytial viruses was determined by real-time PCR. RESULTS: Of
      3209 episodes of suspected pneumonia, viral aetiology was tested in 2917 and
      proportions with influenza virus, human metapneumovirus and respiratory syncytial
      virus were 4.6%, 2.5% and 3.1%, respectively. There were 1653 oropharyngeal swabs
      for PCR testing available from 1814 episodes that fulfilled criteria for CAP,
      yielding 23 first episodes of IA-CAP in the PCV13 and 35 in the in placebo group
      vaccine efficacy for IA-CAP of 34.4% (95% CI -11.1% to 61.2%; p 0.117). Annual
      influenza vaccination was received by 672 (87.2%) in the PCV13 group and 719
      (87.7%) in the placebo group of the confirmed CAP cases. CONCLUSION: In a
      randomized study of 84 496 elderly individuals with a high uptake of influenza
      vaccination, PCV13 was not associated with a statistically significant reduction
      of influenza or virus-associated CAP. Overall incidence of non-influenza viral
      pneumonia was low.

PMID- 29050993
TI  - Psychological causes of autobiographical amnesia: A study of 28 cases.
AB  - Autobiographical amnesia is found in patients with focal or diffuse brain damage
      ("organic amnesia"), but also without overt brain damage (at least when measured
      with conventional brain imaging methods). This last condition is usually named
      dissociative amnesia at present, and was originally described as hysteria.
      Classically and traditionally, dissociative amnesia is seen as a disorder that
      causes retrograde amnesia in the autobiographical domain in the aftermath of
      incidents of major psychological stress or trauma. In the present study one of
      the probably largest published collections of patients (28) with psychogenically
      caused autobiographical amnesia, who were assessed with comprehensive
      neuropsychological tests, will be described and documented in order to identify
      variables which are central for the occurrence of dissociative amnesia. The
      presented cases demonstrate that autobiographical amnesia without direct brain
      damage can have very mixed clinical presentations, causes and consequences. The
      described cases of psychogenic amnesia are clustered according to a number of
      manifestations and features, which include a reduced effort to perform
      cognitively at a normal level, a forensic background, anterograde (instead of
      retrograde) autobiographical amnesia, the fugue condition, concurrent somatic
      diseases, and their appearance in childhood and youth. It is concluded that
      autobiographical amnesia of a psychogenic origin may occur within a variety of
      symptom pictures. For all patients, it probably serves a protective function by
      offering them a mechanism to exit a life situation which appears to them
      unmanageable or adverse.

PMID- 29050995
TI  - Is histologic remission in ulcerative colitis ready for prime time?

PMID- 29050994
TI  - Celiac disease or positive tissue transglutaminase antibodies in patients
      undergoing renal biopsies.
AB  - BACKGROUND: An association between celiac disease and renal diseases has been
      suggested, but the results are controversial. AIMS: To investigate the prevalence
      of celiac disease autoimmunity among individuals undergoing renal biopsies and to
      evaluate whether co-existent celiac autoimmunity influences the clinical outcome
      of the renal disease. METHODS: The prevalence of celiac autoimmunity (previous
      diagnosis of celiac disease or positive tissue transglutaminase antibodies) was
      determined in 827 consecutive patients undergoing kidney biopsies due to clinical
      indications. Up to 15 years' follow-up data on kidney function and co-morbidities
      were obtained. RESULTS: Celiac autoimmunity was found in 45 (5.4%) patients.
      Among the IgA nephropathy patients, 8.2% of had celiac autoimmunity. At the time
      of kidney biopsy and after a median follow-up of 5 to 6 years, renal function
      measured by estimated glomerular filtration rate (eGFR) was inferior in IgA
      nephropathy patients with celiac autoimmunity compared to those without it
      (P=0.048 and P=0.022, respectively). CONCLUSION: The prevalence of celiac
      autoimmunity seems to be high in patients undergoing renal biopsies, especially
      in patients with IgA nephropathy. Such autoimmunity may be associated with worse
      renal function in IgA nephropathy. Hence the co-existence of celiac disease
      should be taken into consideration when treating patients with renal diseases.

PMID- 29050996
TI  - Pancreatic duct cytology, an underused diagnostic tool.

PMID- 29050997
TI  - Transient elastography to assess liver stiffness in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Liver injury during inflammatory bowel disease (IBD) is primarily
      diagnosed by liver biopsy, which has a small but serious risk of severe
      complications. The aim of this study was to assess liver stiffness, and
      subsequently the prevalence and associations of liver fibrosis in IBD patients
      with thiopurine therapy and other clinical factors, by using transient
      elastography (TE). METHODS: In this prospective, international two-center study,
      included IBD-patients underwent TE measurements. Laboratory results and
      medication reports, radiology results and historical liver biopsy results were
      extracted from the patient charts. RESULTS: Transient elastography results of 168
      patients were presented. Moderate and severe fibrosis were detected in 4% (7/168)
      and 1% (1/168) of the cohort, respectively. Factors contributing to lower liver
      stiffness were female gender and (historical) exposure to azathioprine. Further,
      there was a statistical trend towards lower liver stiffness in patients using
      thiopurines overall (4.7 vs. 5.2kPa, p=0.07). Liver stiffness correlated
      positively with waist circumference, liver enzyme tests, hemoglobin and 6
      methylmercaptopurine concentration and negatively with platelet count.
      CONCLUSION: Exposure to thiopurine therapy was not associated with higher liver
      stiffness, although no clinical difference in severity of fibrosis was detected.
      Further research should robustly determine the accuracy of TE as an evaluation of
      liver fibrosis in IBD patients.

PMID- 29050998
TI  - Sedative and antinociceptive effects of different combinations of detomidine and
      methadone in standing horses.
AB  - OBJECTIVE: To evaluate intravenous (IV) detomidine with methadone in horses to
      identify a combination which provides sedation and antinociception without
      adverse effects. STUDY DESIGN: Randomized, placebo-controlled, blinded,
      crossover. ANIMALS: A group of eight adult healthy horses aged (mean +/- standard
      deviation) 7 +/- 2 years and 372 +/- 27 kg. METHODS: A total of six treatments
      were administered IV: saline (SAL); detomidine (5 MUg kg-1; DET); methadone (0.2
      mg kg-1; MET) alone or combined with detomidine [2.5 (MLD), 5 (MMD) or 10 (MHD)
      MUg kg-1]. Thermal, mechanical and electrical nociceptive thresholds were
      measured, and sedation, head height above ground (HHAG), cardiopulmonary
      variables and intestinal motility were evaluated at 5, 15, 30, 45, 60, 75, 90,
      120 and 180 minutes. Normal data were analyzed by mixed-model analysis of
      variance and non-normal by Kruskal-Wallis (p < 0.05). RESULTS: Nociceptive
      thresholds in horses administered methadone with the higher doses of detomidine
      (MMD, MHD) were increased above baseline to a greater degree and for longer
      duration (MMD: 15-30 minutes, MHD: 30-60 minutes) than in horses administered low
      dose with methadone or detomidine alone (MLD, DET: 5-15 minutes). No increases in
      nociceptive thresholds were recorded in SAL or MET. Compared with baseline, HHAG
      was lower for 30 minutes in MMD and DET, and for 45 minutes in MHD. No
      significant sedation was observed in SAL, MET or MLD. Intestinal motility was
      reduced for 75 minutes in MHD and for 30 minutes in all other treatments.
      CONCLUSIONS: Methadone (0.2 mg kg-1) potentiated the antinociception produced by
      detomidine (5 MUg kg-1), with minimal sedative effects. CLINICAL RELEVANCE:
      Detomidine (5 MUg kg-1) with methadone (0.2 mg kg-1) produced antinociception
      without the adverse effects of higher doses of detomidine.

PMID- 29050999
TI  - Chemical capture of impala (Aepyceros melampus): A review of factors contributing
      to morbidity and mortality.
AB  - OBJECTIVE: To review the factors that contribute to morbidity and mortality of
      impala undergoing chemical capture, and discuss how they are potentially
      mitigated. DATABASES USED: PubMed, Science Direct, Google Scholar and
      Onderstepoort Veterinary Academic Hospital records. CONCLUSIONS AND CLINICAL
      RELEVANCE: Impala are an important species of antelope in Africa and are often
      captured during management procedures, veterinary interventions and research
      projects. Chemical capture is a preferred technique over physical capture and
      restraint for veterinary interventions as it allows for easier handling and
      better clinical assessment and treatment. However, this capture technique results
      in high mortality (4%) and morbidity rates (23%), which translates into animal
      welfare and economic concerns. Investigation of environmental, drug and drug
      delivery, and animal factors to elucidate the origin of these high rates was
      reviewed. The greatest risks emanate from the drug and drug delivery factors
      where potent opioids (etorphine and thiafentanil) cause profound respiratory
      compromise, that if left untreated often translates into fatalities. Furthermore,
      the procedure of darting, an essential tool in game capture, can cause
      irreparable fractures and other fatal injuries mainly through accidental
      misplacement of the dart into a long bone, thoracic or peritoneal cavity. Impala
      are anxious and flighty, and this demeanour (animal related factor) can
      contribute towards mortality and morbidity rates. Impala that mount an
      inappropriate stress response to capture tend to die; therefore, procedures that
      induce an intense stress response (awake clinical examinations) should be
      avoided. Sequela of a heightened stress response include capture-induced
      hyperthermia, myopathies, fractures, maladaptation to confinement or new
      environments and death. Impala serve as a useful model for improving immobilizing
      and anaesthetic drug protocols, darting techniques or new methods of remote
      injection in wildlife. However, the risks associated with chemical capture in
      this species should be understood, and all efforts to mitigate these should be
      employed.

PMID- 29051000
TI  - Pulsed inhaled nitric oxide improves arterial oxygenation in colic horses
      undergoing abdominal surgery.
AB  - OBJECTIVE: To evaluate the effect of pulsed inhaled nitric oxide (INO) on
      arterial oxygenation in horses during abdominal surgery. STUDY DESIGN:
      Prospective, randomized, clinical trial. ANIMALS: Thirty horses that underwent
      abdominal surgery at the University Animal Hospital in Uppsala, Sweden. METHODS:
      Anaesthesia was induced according to a standard protocol - romifidine,
      butorphanol, diazepam and ketamine and maintained with isoflurane in oxygen.
      Fifteen horses were administered pulsed INO and 15 served as controls. After
      baseline data collection, pulsed INO delivery commenced. Arterial and venous
      blood were collected and analysed. Cardiorespiratory parameters were measured,
      and oxygen content and F-shunt were calculated. RESULTS: Arterial oxygen tension
      (PaO2) and arterial oxygen saturation (SaO2) increased from 10.9+/-5.7 kPa (82+/
      43 mmHg) and 93+/-6% to 17.3+/-6.9 kPa (134+/-52 mmHg) (p<0.0001) and 98+/-2%
      (p<0.0001), respectively, in horses administered pulsed INO. In the control
      group, PaO2 and SaO2 decreased from 13.9+/-9.1 kPa (104+/-68 mmHg) and 93+/-7% to
      12.1+/-8.6 kPa (91+/-65 mmHg) (p=0.0413) and 91+/-8% (p=0.0256), respectively. At
      the end of anaesthesia, the oxygen content was significantly higher in horses
      administered pulsed INO compared to controls (p=0.0126). The calculated F-shunt
      decreased from 39+/-10% to 27+/-6% (p<0.0001) in horses administered pulsed INO,
      and remained unchanged in controls, 40+/-12% to 44+/-12%. Blood lactate
      concentration decreased (-17+/-21%) in horses administered pulsed INO (p=0.0119),
      whereas no difference was measured in controls (2+/-31%). CONCLUSIONS AND
      CLINICAL RELEVANCE: The present study showed that it is possible to effectively
      reduce the F-shunt and improve arterial oxygenation in horses during abdominal
      surgery by continuous delivery of pulsed INO.

PMID- 29051001
TI  - Episode-based Payment Variation for Urologic Cancer Surgery.
AB  - OBJECTIVE: To investigate payment variation for 3 common urologic cancer
      surgeries and evaluate the potential for applying bundled payment programs to
      these procedures. METHODS: Using 2008-2011 Surveillance, Epidemiology, and End
      Results-Medicare linked data, we identified all beneficiaries aged greater than
      65 years who underwent cystectomy, prostatectomy, or nephrectomy for cancer.
      Total episode payments were determined by aggregating hospital, professional, and
      post-acute care claims from the index surgical hospitalization through 90 days
      post discharge. Total episode payments were then compared to examine hospital
      level-variation within each procedure type and the specific payment components
      (ie, index hospitalization, professional, readmission, and post-acute care)
      driving spending variation. RESULTS: Ninety-day episodes of care were identified
      for 1849 cystectomies, 8770 prostatectomies, and 4304 nephrectomies. We observed
      wide variation in mean episode payments for all 3 conditions (cystectomy mean
      $35,102: range $24,112-$57,238, prostatectomy mean $10,803: range $8,816-$17,877,
      nephrectomy mean $17,475: range $11,681-$26,711). Majority of payment variation
      was attributable to index hospitalization and post-acute care for cystectomy and
      nephrectomy and professional payments for prostatectomy. The most expensive
      hospitals by procedure each demonstrated a unique opportunity for spending
      reduction due to individual differences in component payment patterns between
      hospitals. CONCLUSION: Ninety-day episode payments for urologic cancer surgery
      vary widely across hospitals in the United States. The key drivers of this
      payment variation differ for individual procedures and hospitals. Accordingly,
      hospitals will need individualized data and clinical re-design strategies to
      succeed with implementation of episode-based payment models for urologic cancer
      care.

PMID- 29051002
TI  - Men With Severe Oligospermia Appear to Benefit From Varicocele Repair: A Cost
      effectiveness Analysis of Assisted Reproductive Technology.
AB  - OBJECTIVE: To evaluate the outcomes of men who underwent varicocelectomy for
      total motile sperm count (TMSC) <2 million and to perform a cost-effectiveness
      analysis of intrauterine insemination (IUI) and in vitro fertilization with
      intracyctoplasmic sperm injection after varicocelectomy. METHODS: We
      prospectively collected data of men with TMSC <2 million who underwent
      microsurgical subinguinal varicocelectomy. Men with azoospermia were excluded.
      Serum testosterone, luteinizing hormone, and follicle-stimulating hormone were
      measured preoperatively. Postoperative semen analysis was collected first at 3
      months and then every 3 months thereafter. Cost-effectiveness for assisted
      reproductive technologies was calculated using reported costs. RESULTS: A total
      of 17 men underwent varicocele repair for TMSC <2 million. The mean sperm
      concentration, motility, and TMSC was 1.1 +/- 1.4 million/mL, 15.5% +/- 12.8%,
      and 0.44 +/- 0.54 million prior to varicocelectomy, respectively. After
      varicocelectomy, 14 of 17 men had improvements in TMSC. The mean change in sperm
      concentration, motility, and TMSC was 4.3 +/- 4.7 million/mL, 12% +/- 17.2%, and
      6.0 +/- 8.5 million, respectively. The mean postoperative sperm concentration,
      motility, and TMSC was 5.4 +/- 5.4 million/mL, 27.5% +/- 25.1%, and 6.5 +/- 8.5
      million, respectively. A total of 10 of 17 men had TMSC greater than 2 million.
      Of the 10 men, 1 man achieved spontaneous pregnancy and 7 men underwent a cycle
      of IUI; 2 of the 7 (28.6%) men achieved successful pregnancy with IUI (cost per
      pregnancy: $35,924). CONCLUSION: Varicocelectomy increases TMSC in severely
      oligospermic patients, thus providing previously ineligible couples an
      opportunity to elect for IUI, a less invasive and less expensive alternative to
      in vitro fertilization with intracyctoplasmic sperm injection.

PMID- 29051003
TI  - Spontaneous Regeneration of Nerve Fiber and Irreversibility of Corporal Smooth
      Muscle Fibrosis After Cavernous Nerve Crush Injury: Evidence From Serial
      Transmission Electron Microscopy and Intracavernous Pressure.
AB  - OBJECTIVE: To determine the pathophysiological progresses following bilateral
      cavernous nerve crushing injury, as an index for a treatment point and
      establishment of adequate treatment strategies for neurogenic erectile
      dysfunction. MATERIALS AND METHODS: Thirty-six rats were assigned to 1 of 6
      groups, and bilateral cavernous nerve crushing or sham surgery was performed.
      Functional testing and ultrastructural analyses were performed immediately and at
      7, 14, 21, and 28 days after the cavernous nerve (CN) injury (n = 6). RESULTS:
      Intracavernos pressure lowered progressively from 7 days to 14 days post-injury,
      and histologic staining revealed that the number of neuronal nitric oxide
      synthase-positive nerve fibers on the dorsal penile nerve decreased significantly
      and progressively from 7 days until 21 days post-injury. Furthermore,
      ultrastructural analyses revealed axon loss and demyelination of the CN at 7 and
      14 days post-injury. However, it is followed by partial spontaneous recovery of
      erectile function and regeneration of the CN at 28 days post-injury, suggesting
      that these time points may be useful for evaluating the effects of drug
      treatments. Furthermore, we found that CN injury-induced damage to corporal
      smooth muscle cells was irreversible; therefore, focusing on protecting the
      corpus cavernosum from apoptosis may be more important than nerve protection when
      assessing treatment mechanisms in the CN injury model. CONCLUSION: Our study
      makes a significant contribution to the human diagnostic pathology literature
      because it describes characteristics of relevant tissue in the rat and provides
      information regarding time points that may be useful for future studies of
      pathologic mechanisms or treatment evaluations.

PMID- 29051004
TI  - Assessing Time of Full Renal Recovery Following Minimally Invasive Partial
      Nephrectomy.
AB  - OBJECTIVE: To assess renal function in the operated kidney at different time
      points post partial nephrectomy (PN) and establish the time in which optimal
      recovery occurs. Recovery of renal function post-PN has received significant
      attention. However, the optimal time to determine full recovery has not been
      clearly established. MATERIALS AND METHODS: Renal function following minimally
      invasive (laparoscopic and robotic) PNs performed between 2002 and 2015 was
      reviewed. Patients included in this study had renal function assessed
      preoperatively as well as 3 days, 6-12 weeks, and 1 year post-PN, using a
      combination of estimated glomerular filtration rate (eGFR) from serum creatinine
      and relative renal uptake (RRU) from Tc99m-MAG3 renal scintigraphy. Together,
      eGFR and RRU provide the ipsilateral renal function (IRF) of the operated organ.
      RESULTS: At 6-12 weeks postoperatively, percent preserved eGFR, RRU, and IRF
      (relative to preoperative baselines) were 92.1%, 83.3%, and 77.4% respectively.
      %IRF at 6-12 weeks was significantly improved from %IRF at 3 days
      postoperatively, but did not differ significantly from 1 year postoperatively.
      Furthermore, 89% of patients had RRU values at 6-12 weeks which differed by less
      than 5% from RRU values at 1 year. CONCLUSION: Our data suggest that renal
      function recovery at 6-12 weeks was equivalent to long-term recovery at 1 year in
      the majority of post-PN patients. This has important implications for post-PN
      follow-up, particularly in assessing the functional outcomes utilizing novel
      minimally invasive PN strategies, as well as in planning staged procedures for
      bilateral synchronous renal masses.

PMID- 29051005
TI  - Protective Effect of a Rho-kinase Inhibitor on Bladder Dysfunction in a Rat Model
      of Chronic Bladder Ischemia.
AB  - OBJECTIVE: To investigate the effect of fasudil, a Rho-kinase inhibitor, on
      chronic ischemia-related bladder dysfunction. MATERIALS AND METHODS: Male Sprague
      Dawley rats (16 weeks old) were divided into control, chronic bladder ischemia
      (CBI), and CBI with fasudil treatment (CBI-Fa) groups. The CBI and CBI-Fa groups
      underwent balloon endothelial injury of bilateral iliac arteries and received a
      2% cholesterol diet for 8 weeks after the procedure to induce CBI. The CBI-Fa
      group was given oral fasudil (30 mg/kg/day) using zonde for 8 weeks after the
      procedure. The control group received a regular diet for 8 weeks. After
      cystometry in a conscious state, rats from each group were euthanized, and the
      bladders and common iliac arteries were harvested for pharmacologic and
      histologic examination. RESULTS: Mean wall thickness of the common iliac arteries
      was significantly greater in the CBI group than in controls. Contractile
      responses of muscle strips were significantly lower in CBI group rats than in
      controls. In the CBI group, micturition interval was significantly shorter, and
      bladder capacity was significantly lower compared with those in controls. In the
      CBI-Fa group, arterial wall thickening was significantly suppressed compared with
      the CBI group. Significant improvements in muscle strip contractility and
      cystometric parameters were seen in the CBI-Fa group compared with the CBI group.
      CONCLUSION: Our results suggest that chronic treatment with fasudil could prevent
      neointimal formation in arteries and bladder dysfunction in this rat model.
      Fasudil may be therapeutically useful in protecting bladder function in
      chronically ischemic bladders.

PMID- 29051006
TI  - Re: Deebel et al.: Prostate Cancer in Transgender Women: Incidence,
      Etiopathogenesis, and Management Challenges (Urology 2017;110:166-171).

PMID- 29051007
TI  - Long-term Results of Ventral Penile Curvature Repair in Childhood.
AB  - OBJECTIVE: To assess the postpubertal outcome of ventral penile curvature
      repaired in infancy in terms of recurrence and aesthetics. MATERIALS AND METHODS:
      Postpubertal patients treated for hypospadias and ventral penile curvature in
      infancy at a tertiary medical center were invited to undergo assessment of the
      quality of the repair. Findings were compared between patients with a straight
      penis after skin release and patients who required dorsal plication. RESULTS: The
      cohort included 27 patients of mean age 16.5 years who were reported with
      straight penis after surgery. Postpubertal curvature was found in 6 of 14
      patients (43%) successfully treated by skin release and 10 of 13 patients (77%)
      who underwent dorsal plication (P = .087). Significant curvature (>=30 degrees)
      was found in 1 of 14 patients in the skin-release group and 4 of 13 in the dorsal
      plication group (P = .16). Rates of redo urethroplasty were 2 of 14 (14%) and 5
      of 10 (50%), respectively. Patient satisfaction with the appearance of the penis
      did not differ significantly. CONCLUSION: Ventral penile curvature repaired in
      infancy often recurs after puberty. The need for dorsal plication has a trend
      level association with recurrence of penile curvature in puberty. It might also
      be related to the degree of postpubertal penile curvature and the need for redo
      urethroplasty. Procedure type does not affect patient satisfaction with the
      postpubertal appearance of the penis.

PMID- 29051008
TI  - DNA recombination defects in Kuwait: Clinical, immunologic and genetic profile.
AB  - Defects in DNA Recombination due to mutations in RAG1/2 or DCLRE1C result in
      combined immunodeficiency (CID) with a range of disease severity. We present the
      clinical, immunologic and molecular characteristics of 21 patients with defects
      in RAG1, RAG2 or DCLRE1C, who accounted for 24% of combined immune deficiency
      cases in the Kuwait National Primary Immunodeficiency Disorders Registry. The
      distribution of the patients was as follow: 8 with RAG1 deficiency, 6 with RAG2
      deficiency and 7 with DCLRE1C deficiency. Nine patients presented with SCID, 6
      with OS, 2 with leaky SCID and 4 with CID and granuloma and/or autoimmunity (CID
      G/AI). Eight patients [(7 SCID and 1 OS) (38%)] received hematopoietic stem cell
      transplant (HSCT). The median age of HSCT was 11.5months and the median time from
      diagnosis to HSCT was 6months. Fifty percent of the transplanted patients are
      alive while only 23% of the untransplanted ones are alive.

PMID- 29051009
TI  - Targeting the immune response in atherosclerosis: It's time for clinical trials!

PMID- 29051010
TI  - Response to "Re. Pre-incision urethral plate width does not impact short-term
      tubularized incised plate urethroplasty outcomes".

PMID- 29051011
TI  - Carbon monoxide (CO) inhibits hydrogen peroxide (H2O2)-induced oxidative stress
      and the activation of NF-kappaB signaling in lens epithelial cells.
AB  - Lens epithelial cells (LECs) play a critical role in the maintenance of clear
      crystalline lens. Previously, we reported that heme oxygenase-1 can protect LECs
      from hydrogen peroxide (H2O2)-induced apoptosis and oxidative stress; however, to
      the best of our knowledge, these protection mechanisms have not yet been
      explained. As carbon monoxide (CO) is an active by-product of heme degradation,
      we investigated its cytoprotective mechanism in both H2O2-treated human LECs (SRA
      01/04) and primary rabbit LECs. CO-releasing molecule-3 was used as a CO
      releasing vehicle. The nuclear translocation of nuclear factor kappa B (NF
      kappaB) p65 was monitored by Western blot and immunofluorescence staining. In
      addition, the levels of intracellular reactive oxygen species (ROS),
      antioxidants, and apoptotic molecules (Bax, Bcl-2, and caspase-3) were measured.
      Furthermore, cell apoptosis rate was quantified by flow cytometry. Our results
      disclosed that low concentrations of CO released from CO-releasing molecule-3 can
      attenuate NF-kappaB p65 nuclear translocation, reduce ROS generation, and enhance
      intracellular glutathione and superoxide dismutase levels. Moreover, low
      concentrations of CO inhibited H2O2-induced apoptotic molecules, thereby
      decreasing the apoptosis of LECs. These findings suggest that low concentrations
      of CO protect LECs from H2O2-induced oxidative damage by attenuating NF-kappaB
      p65 nuclear translocation, reducing the generation of ROS and apoptotic
      molecules, and restoring antioxidant enzyme levels, thereby inhibiting LECs
      apoptosis.

PMID- 29051013
TI  - Pericellular interphotoreceptor matrix dictates outer retina critical surface
      tension.
AB  - Retinal detachments create two pathological surfaces, the surface of the outer
      neural retinal, and an apical retinal-pigmented epithelium (RPE) surface. The
      physicochemical properties of these two new surfaces are poorly understood. At a
      molecular level little is known how detachments form, how to optimize
      reattachment, or prevent extension of the detachment. A major limitation is lack
      of information about the biophysical consequences of the retina-RPE separation.
      The primary challenge is determining the molecular properties of the pathological
      interface surfaces. Here, using detached bovine retina, we show that this hurdle
      can be overcome through a combination of biophysical and ultrastructural
      approaches. The outer surface of freshly detached bovine neural retina, and
      isolated molecular components of the outer retina were subjected to: 1) Contact
      angle goniometry to determine the critical surface tension of the outer retinal
      surface, isolated insoluble interphotoreceptor matrix (IPM) and purified
      interphotoreceptor retinoid binding protein (IRBP); 2) Multiple attenuated
      internal reflectance infrared (MAIR-IR) spectroscopy was used to characterize the
      molecular composition of the retinal surface. MAIR-IR depth penetration was
      established through ellipsometric measurement of barium-stearate films. Light
      microscopy, immunohistochemistry and electron microscopy defined the structures
      probed spectroscopically. Furthermore, the data were correlated to IR spectra of
      docosahexaenoic acid, hyaluronan, chondroitin-6-sulfate and IRBP, and imaging by
      IR-microscopy. We found that the retinal critical surface tension is 24 mN/m,
      similar to isolated insoluble IPM and lower than IRBP. Barium-stearate
      calibration studies established that the MAIR-IR spectroscopy penetration depth
      was 0.2 MUm. Ultrastructural observations and MAIR-IR studies of isolated outer
      retina components determined that the pericellular IPM coating the outer retinal
      surface is primarily responsible for these surface properties. The critical
      surface tension of detached bovine retina is dictated not by the outer segments,
      but by a pericellular IPM covering the outer segment tips.

PMID- 29051014
TI  - Furan fatty acids - Beneficial or harmful to health?
AB  - Furan fatty acids are found in plants, algae, and fish, and reported to have some
      positive health benefits, including anti-oxidant and anti-inflammatory
      activities, and inhibition of non-enzymatic lipid peroxidation. A major
      metabolite of furan fatty acids, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic
      acid (CMPF), has been reported to be increased in patients who progress from
      prediabetes to type 2 diabetes, although CMPF is not necessarily associated with
      impaired glucose metabolism. Other studies report that CMPF levels are lower in
      subjects with diabetes than control subjects. Plasma CMPF levels increase in
      subjects who consume fish or fish oil, and in patients with renal failure. It is
      not known where furan fatty acids are converted to CMPF and it is speculated that
      this might be a result of microbiome activity. The plasma levels reported for
      CMPF in healthy, diabetic and patients with renal disease vary by factors of more
      than 100-fold within each of these three groups, so measurement error appears to
      be limiting the ability to interpret studies. This review explores these
      controversies and raises questions about whether CMPF is a marker for healthy
      diets or indeed associated with diabetes and renal health. The review concludes
      that, on balance, furan fatty acids are beneficial for health.

PMID- 29051015
TI  - An RCT to Facilitate Implementation of School Practices Known to Increase
      Physical Activity.
AB  - INTRODUCTION: Although comprehensive school-based physical activity interventions
      are efficacious when tested under research conditions, they often require
      adaptation in order for implementation at scale. This paper reports the
      effectiveness of an adapted efficacious school-based intervention in improving
      children's moderate to vigorous physical activity. The impact of strategies to
      support program implementation was also assessed. DESIGN: A cluster RCT of low
      socioeconomic elementary schools in New South Wales, Australia.
      SETTING/PARTICIPANTS: Consenting schools were randomized (25 intervention, 21
      control) using a computerized random number function. Follow-up measures were
      taken at 6 months post-randomization (May-August 2015) by blinded research
      assistants. The multicomponent school-based intervention, based on an efficacious
      school-based physical activity program (Supporting Children's Outcomes using
      Rewards, Exercise and Skills), consisted of four physical activity strategies and
      seven implementation support strategies. The intervention was adapted for
      scalability and delivery by a local health service over 6 months. The primary
      outcome was accelerometer assessed, student mean daily minutes spent in moderate
      to vigorous physical activity. Physical education lesson quality and other school
      physical activity practices were also assessed. RESULTS: Participants (n=1,139,
      49% male) were third- through sixth-grade students at follow-up (May-August
      2015). Valid wear time and analysis of data were provided for 989 (86%)
      participants (571 intervention, 568 control). At 6-month follow-up, there were no
      significant effects in overall daily minutes of moderate to vigorous physical
      activity between groups (1.96 minutes, 95% CI= -3.49, 7.41, p=0.48). However,
      adjusted difference in mean minutes of overall vigorous physical activity (2.19,
      95% CI=0.06, 4.32, p=0.04); mean minutes of school day moderate to vigorous
      physical activity (2.90, 95% CI=0.06, 5.85, p=0.05); and mean minutes of school
      day vigorous physical activity (1.81, 95% CI=0.78, 2.83, p<=0.01) were
      significantly different in favor of the intervention group. Physical education
      lesson quality and school physical activity practices were significantly
      different favoring the intervention group (analyzed October 2015-January 2016).
      CONCLUSIONS: The modified intervention was not effective in increasing children's
      overall daily minutes of moderate to vigorous physical activity, when adapted for
      implementation at scale. However, the intervention did improve daily minutes of
      vigorous physical activity and school day moderate to vigorous physical activity,
      lesson quality, and school physical activity practices. TRIAL REGISTRATION:
      Australian New Zealand Clinical Trials Registry: ACTRN12615000437561.

PMID- 29051012
TI  - Vergence driven accommodation with simulated disparity in myopia and emmetropia.
AB  - The formation of focused and corresponding foveal images requires a close synergy
      between the accommodation and vergence systems. This linkage is usually decoupled
      in virtual reality systems and may be dysfunctional in people who are at risk of
      developing myopia. We study how refractive error affects vergence-accommodation
      interactions in stereoscopic displays. Vergence and accommodative responses were
      measured in 21 young healthy adults (n=9 myopes, 22-31 years) while subjects
      viewed naturalistic stimuli on a 3D display. In Step 1, vergence was driven
      behind the monitor using a blurred, non-accommodative, uncrossed disparity
      target. In Step 2, vergence and accommodation were driven back to the monitor
      plane using naturalistic images that contained structured depth and focus
      information from size, blur and/or disparity. In Step 1, both refractive groups
      converged towards the stereoscopic target depth plane, but the vergence-driven
      accommodative change was smaller in emmetropes than in myopes (F1,19=5.13,
      p=0.036). In Step 2, there was little effect of peripheral depth cues on
      accommodation or vergence in either refractive group. However, vergence responses
      were significantly slower (F1,19=4.55, p=0.046) and accommodation variability was
      higher (F1,19=12.9, p=0.0019) in myopes. Vergence and accommodation responses are
      disrupted in virtual reality displays in both refractive groups. Accommodation
      responses are less stable in myopes, perhaps due to a lower sensitivity to
      dioptric blur. Such inaccuracies of accommodation may cause long-term blur on the
      retina, which has been associated with a failure of emmetropization.

PMID- 29051016
TI  - Patterns of Prostate-Specific Antigen Test Use in the U.S., 2005-2015.
AB  - INTRODUCTION: Recommendations for prostate-specific antigen-based screening for
      prostate cancer are placing increasing emphasis on men aged 55-69 years. The goal
      of the current study is to describe patterns of population-based prostate
      specific antigen testing with details about that age group. METHODS: National
      Health Interview Surveys from 2005 to 2015 were analyzed in 2017 to estimate
      routine prostate-specific antigen testing in the past year from self-reported
      data by age group (40-54, 55-69, >=70 years), and also by risk group, defined as
      African American men or men with a family history of prostate cancer versus other
      men. Differences between successive survey years by age and risk groups were
      assessed by predicted margins and rate ratios with 99% CIs, using logistic
      regressions. RESULTS: Prostate-specific antigen testing among men aged 55-69
      years decreased from a high of 43.1% (95% CI=40.3, 46.1) in 2008 to a low of
      32.8% (95% CI=30.8, 34.7) in 2013, with no significant change in 2015 at 33.8%
      (95% CI=31.3, 36.4). Men aged >=70 years had consistently high prevalence in all
      survey years, ranging from 51.1% in 2008 to 36.4% in 2015. African American men,
      men with a family history of prostate cancer, and other men showed a 5% absolute
      decrease over time, but this reduction was significant only in other men.
      CONCLUSIONS: Despite decreases, the absolute change in prostate-specific antigen
      testing for men aged 55-69 years was small (9.3%) over the study period. Men aged
      >=70 years, for whom the benefits are unlikely to exceed the harms, continue to
      have consistently high testing prevalence.

PMID- 29051017
TI  - Low Prevalence of Criteria for Early Screening in Young-Onset Colorectal Cancer.

PMID- 29051019
TI  - The American College of Preventive Medicine Policy Recommendations on Public
      Health Funding.
AB  - The American College of Preventive Medicine Policy Committee makes policy
      guidelines and recommendations on Preventive Medicine and Public Health topics
      for Public Health decision makers. After a review of the current evidence
      available in 2016, the College is providing policy recommendations designed to
      inform public health investment. The American College of Preventive Medicine
      advocates for policies that recognize the health and economic value of public
      health funding and promote investment in these vital capabilities. Shortfalls in
      public health infrastructure, particularly workforce funding, must be corrected
      to ensure lasting benefits. Contingency funding for public health emergencies
      should be established and fully funded to adequately respond to emerging threats.

PMID- 29051018
TI  - Access to Employee Wellness Programs and Use of Preventive Care Services Among
      U.S. Adults.
AB  - INTRODUCTION: There is little research at the national level on access to
      employee wellness programs and the use of preventive care services. This study
      examined the use of seven preventive care services among U.S working adults with
      access to employee wellness programs. METHODS: The study population comprised
      17,699 working adults aged >=18 years, obtained from the 2015 National Health
      Interview Survey. Multivariate logistic regression models examined the
      relationship between access to employee wellness programs and use of seven
      preventive care services: influenza vaccination, blood pressure check, diabetes
      check, cholesterol check, Pap smear test, mammogram, and colon cancer screening.
      Data analysis began in Fall 2016. RESULTS: Overall, 46.6% of working adults
      reported having access to employee wellness programs in 2015. Working adults with
      access to employee wellness programs had higher odds of receiving influenza
      vaccination (OR=1.57, 95% CI=1.43, 1.72, p<0.001), blood pressure check (OR=2.46,
      95% CI=2.17, 2.78, p<0.001), diabetes check (OR=1.30, 95% CI=1.12, 1.50,
      p<0.001), cholesterol check (OR=1.48, 95% CI=1.33, 1.67, p<0.001), and mammogram
      (OR=1.57, 95% CI=1.24, 1.98, p<0.001). However, there was no significant
      difference between access to employee wellness programs and the use of Pap smear
      test and colon cancer screening services. CONCLUSIONS: Using a nationally
      representative sample of individuals, this study found a positive association
      between access to employee wellness programs and the use of preventive care
      services. The results support favorable policies to encourage implementing
      wellness programs in all worksites, especially those with <50 employees.

PMID- 29051020
TI  - Draft genome sequences of three multidrug-resistant Cutibacterium (formerly
      Propionibacterium) acnes strains isolated from acne patients, China.
AB  - OBJECTIVES: Cutibacterium acnes (formerly Propionibacterium acnes), an anaerobic
      Gram-positive bacterium, is a skin commensal and is considered to be associated
      with acne. Here we report the draft genome sequences of three multidrug-resistant
      (MDR) C. acnes strains (CA17, CA39 and CA51) isolated from skin lesions of acne
      patients in China. METHODS: The whole genomes of the three MDR C. acnes strains
      were sequenced using an Illumina HiSeq 2500 platform. De novo assembly and
      annotation were performed with SPAdes 3.5.0 and NCBI Prokaryotic Genome
      Annotation Pipeline (PGAP), respectively. RESULTS: The genomes of the three
      strains are as follows: 2 488 255bp containing 2494 genes and 2266 coding
      sequences (CDSs) for CA17; 2 484 088bp containing 2515 genes and 2376 CDSs for
      CA39; and 2 483 437bp containing 2515 genes and 2372 CDSs for CA51. Each strain
      has 45 tRNAs and 3 rRNAs. CONCLUSIONS: The genome sequences of the three MDR C.
      acnes strains may provide foundations for further research into the resistance
      mechanisms of antibiotic-resistant C. acnes strains and their role in disease
      pathogenesis.

PMID- 29051021
TI  - Anti-Platelet-Derived Growth Factor Receptor Alpha Chain Antibodies Predict for
      Response to Nilotinib in Steroid-Refractory or -Dependent Chronic Graft-Versus
      Host Disease.
AB  - Imatinib has clinical activity in chronic graft-versus-host disease (cGVHD), a
      significant complication of allogeneic hematopoietic cell transplant. Nilotinib
      is a tyrosine kinase inhibitor that targets the same receptors as imatinib but
      with different affinities. We tested the hypothesis that nilotinib is safe and
      has clinical activity in cGVHD. Thirty-three participants were enrolled in a
      phase I/II dose escalation and dose extension clinical trial of nilotinib for the
      treatment of steroid-refractory or- dependent cGVHD (ClinicalTrials.gov,
      NCT01155817). We assessed safety, clinical response, and pretreatment anti
      platelet-derived growth factor receptor alpha chain (anti-PDGFRA) antibody
      levels. The 200-mg dose was identified as the maximum tolerated dose and used for
      the phase II dose extension study. At 6 months the incidence of failure-free
      survival (FFS), cGVHD progression, and nilotinib intolerance resulting in its
      discontinuation was 50%, 23%, and 23%, respectively. cGVHD responses in skin,
      joints, and mouth were observed at 3 and 6 months based on improvement in
      respective National Institutes of Health organ severity scores. Pretreatment anti
      PDGFRA antibody levels >= .150 optical density as measured by ELISA correlated
      with longer FFS time (P < .0005) and trended with time until cGVHD progression (P
      < .06) but not drug intolerance. Nilotinib may be effective for corticosteroid
      resistant or -refractory cGVHD in some patients, but its use is limited by
      intolerable side effects. Selection of patients with high pretreatment anti
      PDGFRA antibody levels might improve the risk-to-benefit ratio of nilotinib and
      better justify its side effects.

PMID- 29051022
TI  - Impact of Allogeneic Stem Cell Transplantation in First Complete Remission in
      Acute Myeloid Leukemia: A National Population-Based Cohort Study.
AB  - To examine the outcomes of allogeneic stem cell transplantation (HSCT) in first
      complete remission (CR1) compared with chemotherapy alone in a population-based
      setting, we identified a cohort of patients with acute myeloid leukemia (AML)
      aged 15 to 70 years diagnosed between 2000 and 2014 in Denmark. Using the Danish
      National Acute Leukemia Registry, we compared relapse risk, relapse-free survival
      (RFS), and overall survival (OS) between patients with unfavorable cytogenetic
      features receiving postremission therapy with conventional chemotherapy only
      versus those undergoing HSCT in CR1. To minimize immortal time bias, we performed
      Cox proportional hazards regression, included date of allogeneic HSCT as a time
      dependent covariate, and stratified the results by age (<60 or >=60 years) and
      cytogenetic risk group. Overall, 1031 patients achieved a CR1. Of these, 196
      patients (19%) underwent HSCT. HSCT was associated with a lower relapse rate (24%
      versus 49%) despite a similar median time to relapse (287 days versus 265 days).
      In all subgroups, the risk of relapse was lower and both RFS and OS were superior
      in recipients of HSCT (OS, adjusted mortality ratios: all patients, .54 [95%
      confidence interval (CI), .42-.71]; patients age <60 years, .58 [95% CI, .42
      .81]; patients age >=60 years, .42 [95% CI, .26-.69]; patients with intermediate
      risk cytogenetics, .63 [95% CI, .43-.87]; patients with adverse-risk
      cytogenetics, .40 [95% CI, .24-.67]). In conclusion, in this population-based
      nationwide cohort study, HSCT was associated with improved survival in both
      younger and older patients and in patients with both intermediate and adverse
      cytogenetic risk.

PMID- 29051023
TI  - Unlocking the Complex Flavors of Dysgeusia after Hematopoietic Cell
      Transplantation.
AB  - Dysgeusia is a frequently occurring symptom after hematopoietic cell
      transplantation (HCT) that has important long-term effects on physical,
      nutritional, and immunologic recovery, as well as on quality of life. Despite the
      relevance of this symptom, the study of dysgeusia in patients undergoing HCT has
      been limited, owing in part to its complexity. In this article, we review normal
      taste function and its clinical evaluation, discuss how dysgeusia uniquely
      affects patients undergoing HCT, and examine distinct, transplantation-related
      contributors to dysgeusia that may help elucidate strategies to ultimately reduce
      this symptom burden after transplantation.

PMID- 29051024
TI  - Busulfan-Dependent Hepatotoxicity of Antithymocyte Globulin Formulations During
      Conditioning for Hematopoietic Stem Cell Transplantation.

PMID- 29051025
TI  - IsomiR processing during differentiation of myelogenous leukemic cell line K562
      by phorbol ester PMA.
AB  - Chronic myelocytic leukemia cell line K562 undergoes differentiation by phorbol
      esters to megakaryocytes and we have used this system to understand miRNA
      processing leading to isomiR generation. PMA treatment significantly altered the
      production of miRNA in K562 cells. Expression of 24.4% of miRNAs were found to be
      stimulated whereas expression of 10% miRNAs were inhibited by PMA treatment. Our
      results suggest that miRNA precursors are processed into isomiRs in a
      deterministic manner. The relative levels of different isomiRs of a miRNA
      remained mainly unchanged even after PMA treatment irrespective of overall
      changes in expression (either up-regulation or down-regulation). However, not all
      miRNAs behave in the same way, about 7% showed a variation of isomiR profiles
      after PMA treatment. Most of the later class of miRNAs were found to be oncogenic
      miRNAs. Further, it was also found that number of isomiRs was independent of
      abundance of a miRNA. Functional importance of different isomiRs was demonstrated
      using three different isomiRs of miR-22. Our results showed that different
      isomiRs could inhibit expression of targets genes with different efficiencies.
      Our study suggests that the heterogeneity of a miRNA population generated during
      processing is in general regulated and that variation in the generation of an
      isomiR can be a functionally important regulatory feature.

PMID- 29051026
TI  - Mutational analysis of the androgen receptor (NR3C4) gene in patients with 46,XY
      DSD.
AB  - Androgen insensitivity syndrome (AIS) is an X-linked disorder caused by mutations
      in the NR3C4 gene, which encodes the androgen receptor (AR). In this study, we
      performed mutational analyses to identify AR molecular defects, in individuals
      with 46,XY disorders of sex development (46,XY DSD) and a presumptive diagnosis
      of AIS. Eighteen different gene mutations, including seven previously unreported
      new variants, were detected in 26 unrelated cases. These included two deletion
      mutations (P49fs*185 and E308f*320) in exon 1 and five substitution mutations
      (p.S792P, p.D829G, p.R832P, p.L839F, and p.K906E) located in the steroid-binding
      domain. Expression analyses of mutants generated by site-directed mutagenesis
      indicated that these new gene variants impaired AR function by affecting its
      binding activity. Seventeen of 18 mutations likely lead to reduced or absent
      responses to androgens, which may in turn account for the different degrees of
      undermasculinization observed. Our study provides insight into the functional
      consequences of these mutations.

PMID- 29051027
TI  - The conception of the ABCD study: From substance use to a broad NIH
      collaboration.
AB  - Adolescence is a time of dramatic changes in brain structure and function, and
      the adolescent brain is highly susceptible to being altered by experiences like
      substance use. However, there is much we have yet to learn about how these
      experiences influence brain development, how they promote or interfere with later
      health outcomes, or even what healthy brain development looks like. A large
      longitudinal study beginning in early adolescence could help us understand the
      normal variability in adolescent brain and cognitive development and tease apart
      the many factors that influence it. Recent advances in neuroimaging, informatics,
      and genetics technologies have made it feasible to conduct a study of sufficient
      size and scope to answer many outstanding questions. At the same time, several
      Institutes across the NIH recognized the value of collaborating in such a project
      because of its ability to address the role of biological, environmental, and
      behavioral factors like gender, pubertal hormones, sports participation, and
      social/economic disparities on brain development as well as their association
      with the emergence and progression of substance use and mental illness including
      suicide risk. Thus, the Adolescent Brain Cognitive Development study was created
      to answer the most pressing public health questions of our day.

PMID- 29051028
TI  - Social touch interacts with infants' learning of auditory patterns.
AB  - Infants' experiences are defined by the presence of concurrent streams of
      perceptual information in social environments. Touch from caregivers is an
      especially pervasive feature of early development. Using three lab experiments
      and a corpus of naturalistic caregiver-infant interactions, we examined the
      relevance of touch in supporting infants' learning of structure in an altogether
      different modality: audition. In each experiment, infants listened to sequences
      of sine-wave tones following the same abstract pattern (e.g., ABA or ABB) while
      receiving time-locked touch sequences from an experimenter that provided either
      informative or uninformative cues to the pattern (e.g., knee-elbow-knee or knee
      elbow-elbow). Results showed that intersensorily redundant touch supported
      infants' learning of tone patterns, but learning varied depending on the
      typicality of touch sequences in infants' lives. These findings suggest that
      infants track touch sequences from moment to moment and in aggregate from their
      caregivers, and use the intersensory redundancy provided by touch to discover
      patterns in their environment.

PMID- 29051029
TI  - Recent advances in localized RCC: A focus on VEGF and immuno-oncology therapies.
AB  - Recent advances in advanced renal cell cancer (RCC) research have produced new
      drugs and therapies for patients with metastatic disease leading to higher
      response rates, improvements in progression-free survival, and longer overall
      survival. These advances have yet to be realized in patients with early-stage
      kidney cancer, and to date, no drug has been approved for the adjuvant treatment
      of localized kidney cancer. The current standard of care for localized high-risk
      kidney cancers is resection of the primary tumor. Here, we review the results of
      recently completed adjuvant vascular endothelial growth factor receptor 2
      (VEGFR2) tyrosine kinase inhibitor (TKI) trials in RCC that have been reported,
      or are awaiting results. Further, we discuss the new immune checkpoint inhibitor
      adjuvant trials planned. There is hope that these trials may lead to new options
      and longer survival for patients with localized high-risk kidney cancer.

PMID- 29051030
TI  - Posttherapeutic skeletal muscle mass recovery predicts favorable prognosis in
      patients with advanced urothelial carcinoma receiving first-line platinum-based
      chemotherapy.
AB  - OBJECTIVES: Sarcopenia, decreased skeletal muscle mass (SMM), is an adverse
      prognostic factor in patients with advanced urothelial carcinoma (aUC). Given
      that SMM is variable depending on disease and patient conditions, changes in SMM
      over the course of treatments may be also prognostic. We investigated the
      prognostic role of posttherapeutic SMM recovery (PSR) in patients with aUC
      receiving first-line platinum-based chemotherapy. MATERIALS AND METHODS: This
      retrospective study included 72 consecutive patients with aUC receiving first
      line platinum-based chemotherapy. Skeletal muscle index (SMI) was measured on
      computed tomography images taken before the initiation of and immediately after 2
      cycles of chemotherapy. DeltaSMI was calculated as [(posttherapeutic SMI -
      pretherapeutic SMI)/pretherapeutic SMI] * 100, and PSR was defined as DeltaSMI
      >0. Variables associated with progression-free survival (PFS) and overall
      survival (OS) were evaluated. RESULTS: During the follow-up (median, 18mo for
      survivors), 60 (83%) patients progressed (2-year PFS, 17%) and 55 (76%) died (2
      year OS, 24%). DeltaSMI was significantly associated with chemotherapy response
      (P = 0.012), and was an independent predictor for both PFS (hazard ratio [HR] =
      0.94, P<0.001) and OS (HR = 0.93, P<0.001). A total of 15 (21%) patients with PSR
      demonstrated significantly longer PFS and OS than those without PSR (both
      P<0.001). On multivariate analysis, PSR was an independent favorable predictor
      for both PFS (HR = 0.24, P<0.001) and OS (HR = 0.21, P<0.001). Incorporation of
      PSR into the Bajorin's and Galsky's models improved their c-indices (0.611-0.650,
      and 0.690-0.708, respectively). CONCLUSIONS: PSR is a novel prognostic factor in
      patients with aUC receiving first-line platinum-based chemotherapy.

PMID- 29051031
TI  - Inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor
      development in preterm neonates: A Systematic Review.
AB  - OBJECTIVE: To provide a systematic review investigating the role of inflammatory
      molecules and neurotrophic factors as biomarkers of neuropsychomotor development
      in preterm neonates. DATA SOURCE: Databases including PubMed, BIREME, and Scopus
      were systematically searched. Observational studies, as well as transversal, and
      cohort studies using human subjects published from 1990 to September 2017 were
      eligible for inclusion. Two authors independently identified eligible studies and
      analyzed their characteristics, quality, and accuracy in depth. DATA SYNTHESIS:
      11 eligible studies clearly investigated the association between peripheral
      inflammation and motor and/or cognitive development in preterm infants. However,
      the selected populations differed in relation to the events associated with
      prematurity and the risk factors to abnormal motor and/or cognitive development.
      These studies measured circulating levels of cytokines, chemokines, adhesion
      molecules, acute phase proteins, and growth factors. The most commonly analyzed
      proteins were IL-1beta, IL-6, TNF, CCL5/RANTES, CXCL8/IL-8, IGFBP-1, and VEGF. In
      seven of the eligible studies, plasma levels of IL-6 correlated with development
      delay. Two studies reported correlation between CXCL8/IL-8 plasma levels with
      cognitive and motor delay. In one study, higher levels of MCP-1/CCL2 were
      associated with better cognitive and motor outcome. CONCLUSION: There is
      preliminary evidence indicating that circulating inflammatory molecules are
      associated with motor and cognitive development in preterm neonates, even
      considering different populations.

PMID- 29051032
TI  - FTH1 expression is affected by promoter polymorphism and not DNA methylation in
      response to DHV-1 challenge in duck.
AB  - Ferritin heavy polypeptide 1 (FTH1) plays a pivotal role in response to viral
      infections. FTH1 expression is modulated by various pathogens, but the regulatory
      mechanisms are unknown. We firstly construct duck hepatitis virus 1 (DHV-1)
      infection model, including morbid ducklings, non-morbid ducklings and control
      ducklings. Then the mRNA expression of duck FTH1 (duFTH1) was measured mRNA
      expression of duck FTH1 (duFTH1) in the liver and spleen after duck hepatitis
      virus 1 (DHV-1) infection using quantitative polymerase chain reaction (qPCR) and
      found that duFTH1 mRNA was down-regulated significantly in morbid ducklings
      (liver, P < 0.01; spleen, P < 0.05) compared with the control ducklings. We also
      found that duFTH1 expression was significantly higher in the spleen (P < 0.01)
      and liver (P < 0.05) of non-morbid ducklings than in morbid ducklings. Moreover,
      DNA methylation of the duFTH1 promoter was examined by bisulfite sequencing (BSP)
      and we found that the duFTH1 promoter was hypomethylated, the relative
      methylation was only 5.9% and 2.0% in the morbid ducklings and non-morbid
      ducklings, respectively. The promoter contained a -55 C/T mutation in 75% of non
      morbid ducklings, and this polymorphism affected promoter activity. Further
      analysis suggested that this mutation altered the binding site of the
      transcription factor NRF1. Binding of NRF1 to the FTH1 promoter was confirmed by
      electrophoretic mobility shift assay (EMSA) analysis. Thus, our findings revealed
      the NRF1 was a negative regulator, and lossed of binding of NRF1 to duFTH1
      promoter due to -55C/T mutation enhances duFTH1 expression in non-morbid ducks,
      which provided molecular insights into the effect of duFTH1 expression via
      promoter polymorphisms, but not DNA methylation, in response to DHV-1 challenge.

PMID- 29051033
TI  - Description of analytical method and clinical utility of measuring serum 7-alpha
      hydroxy-4-cholesten-3-one (7aC4) by mass spectrometry.
AB  - BACKGROUND: Imbalance of bile acids (BA) homeostasis in the gastrointestinal
      tract can lead to chronic diarrhea or constipation when BA in the colon are in
      excess or low, respectively. Since both disturbances of bowel function can result
      from other etiologies, identifying BA imbalance is important to tailor treatment
      strategies. Serum concentrations of 7-alpha-hydroxy-4-cholesten-3-one (7aC4), a
      precursor in bile acid synthesis, reflect BA homeostasis. Here we describe a
      method to accurately measure serum 7aC4 and evaluate the clinical utility in
      patients with diarrhea or constipation phenotypes. METHODS: Serum 7aC4 is
      measured after acetonitrile protein precipitation using C18 liquid
      chromatography, tandem mass spectrometry, and deuterium-labeled 7aC4 internal
      standard. Assay performance including linearity, precision, and accuracy was
      assessed using waste serum samples. The reference interval was established in
      healthy individuals without BA-altering conditions or medications. Clinical
      performance was assessed in patients with irritable bowel syndrome. RESULTS: The
      method precisely and accurately measured 7aC4 in human serum from 1.4-338ng/mL
      with no ion suppression or interference from related 7-keto-cholesterol. Central
      95th percentile reference interval was 2.5-63.2ng/mL. Lower serum 7aC4 was found
      in patients with constipation with sensitivity/specificity of 79%/55% compared to
      healthy controls. Higher 7aC4 was found in patients with bile acid diarrhea (BAD)
      compared to those without BAD with sensitivity/specificity of 82%/53%.
      CONCLUSIONS: We have developed a sensitive and precise assay for measuring the
      concentration of 7aC4 in serum. The assay can be used to screen for diarrhea
      caused by bile acid malabsorption.

PMID- 29051034
TI  - Pre-operative and post-operative changes in CRP and other biomarkers sensitive to
      inflammatory status in patients with severe obesity undergoing laparoscopic
      sleeve gastrectomy.
AB  - INTRODUCTION: C-reactive protein (CRP) is often elevated in patients living with
      severe obesity (BMI>=35kg/m2). However, there is limited information on how CRP,
      and other inflammation responsive biomarkers, change in response to weight loss
      following laparoscopic sleeve gastrectomy (LSG). We studied how CRP, ferritin and
      albumin change following LSG surgery in relation to obesity, metabolic syndrome
      (MetS) ATPIII risk components and diabetes mellitus (DM). METHODS: Laboratory
      parameters (including CRP) were examined in 197 patients prior to LSG, and at 6,
      12, 18 and 24months. Changes in laboratory parameters, and laboratory
      investigations, were also examined in a 125 patient subgroup at both pre-LSG and
      at the 12month follow-up visit. RESULTS: All patients had BMI>=35kg/m2. CRP
      levels positively correlated with BMI (r=0.171, p=0.016) and alkaline phosphatase
      (ALP; r=0.309; P<0.001), but negatively correlated with alanine aminotransferase
      (ALT; r=-0.260; P<0.001) and albumin (r=-0.358; P<0.001). LSG significantly
      reduced CRP and ferritin, which were maintained for at least 24months. At
      12months post-LSG there was a significant decrease in weight (kgs) (p<0.001), CRP
      (p<0.001), ferritin (p=0.004), and various MetS risk components (p<0.001) but not
      albumin (p=0.057). Changes in CRP also correlated with changes in weight
      (r=0.233, p=0.018) and ALP (r=0.208, p=0.034) but not albumin (r=-0.186, p=0.058)
      or ferritin (r=0.160, p=0.113) after LSG. CONCLUSION: The negative correlation
      between CRP and albumin levels in obesity may indicate a low grade inflammatory
      process affecting both. LSG related weight loss decreased CRP and ferritin,
      likely explained by improvement in inflammatory status.

PMID- 29051035
TI  - Stability of proinsulin in whole blood.
AB  - Proinsulin, the precursor for insulin, is secreted in higher concentrations when
      beta-cells are under stress and previous studies have shown that elevated
      proinsulin could be used as a marker for individuals in a pre-diabetic state. The
      aim of this study was to assess the stability of proinsulin across a wide
      concentration range (3-882 and 2-187pmol/L; total and intact proinsulin
      respectively) in whole blood to determine whether it could be used in routine
      clinical care. 51 subjects (26 normal glucose tolerance, 17 impaired glucose
      tolerance and 8 type 2 diabetes) had blood taken into EDTA tubes at 0, 60 &
      120min following a glucose load. The samples were kept at room temperature (~20
      degrees C) with aliquots taken, centrifuged and frozen at 0, 24, 48 and 72h.
      Comparison of the combined data (pre and post-glucose load) of baseline with 72h
      as a percentage of baseline gave an average of 123% (95% CI: 119-127) and 107%
      (95% CI: 105-109) for total and intact proinsulin respectively. A small change in
      the stability of total proinsulin was observed whilst there was no clinical
      difference over the 72h period for intact proinsulin.

PMID- 29051036
TI  - Characterization of disease burden, comorbidities, and treatment use in a large,
      US-based cohort: Results from the Corrona Psoriasis Registry.
AB  - BACKGROUND: Psoriasis is an immunodysregulatory inflammatory disease associated
      with comorbidities affecting quality of life. With the advent of new treatments,
      there is growing need to assess the long-term safety and efficacy of treatments
      in a real-world setting. OBJECTIVE: The objective of the Corrona Psoriasis
      Registry is to study the comparative safety and efficacy of Food and Drug
      Administration-approved biologic treatments. METHODS: A cross-sectional study of
      patients enrolled in the registry, who initiated or switched to a systemic
      therapy at enrollment or previous 12 months. Descriptive characteristics
      (demographics, clinical and patient-reported outcomes, comorbidities, and
      treatment history) were examined at registry enrollment. RESULTS: As of October
      1, 2016, there were 1942 patients enrolled in the registry: 23% on apremilast, 4%
      on other nonbiologic systemic medications, 25% on interleukin (IL) 17A
      inhibitors, 22% on an IL-12/23 inhibitor, and 26% on tumor necrosis factor
      inhibitors. Overall, mean disease duration was 15.6 years, and 40% had a
      concurrent psoriatic arthritis diagnosis. About 66% had >3% body surface area
      involvement and 49% had a moderate or severe Investigator Global Assessment.
      LIMITATIONS: Selection and channeling bias can result in potential confounding
      that needs to be addressed in modeled analyses. CONCLUSION: This disease-based
      registry cohort represents a population exposed to multiple therapies, long
      disease duration, and multiple comorbidities and can be used to examine
      comparative safety and efficacy of various therapies.

PMID- 29051038
TI  - Image Guided Radiation Therapy Strategies for Pelvic Lymph Node Irradiation in
      High-Risk Prostate Cancer: Motion and Margins.
AB  - PURPOSE: To quantify the relative motion of the pelvic lymph nodes (LNs), seminal
      vesicles (SV) and prostate and define indicative margins for image-guided
      radiotherapy based on bony anatomy or prostate correction strategies for a 3 or 6
      degrees-of-freedom couch. METHODS AND MATERIALS: Nineteen patients had a planning
      computed tomography (CT) scan followed by a mean of 11 repeated CT scans during
      radiation therapy. The prostate, SV, and external and internal iliac LN regions
      on the left and right were outlined on each CT scan. Systematic and random
      uncertainties were determined along with correlations between the motions of
      these regions. The clinical target volume to planning target volume margins
      required to take only motion into account were calculated for each guidance
      method. RESULTS: For bone guidance, motion of the prostate and LNs was largely
      uncorrelated. Margins to compensate for motion (left-right, superior-inferior,
      anterior-posterior, in cm) based on a 3-DOF couch were as follows: prostate (0.2,
      0.6, 0.8), SV (0.4, 0.9, 1.0), and LNs (0.3, 0.4, 0.6). For prostate guidance,
      margins were calculated for correlated motion: prostate (0, 0, 0), SV (0.3, 0.5,
      0.4), and LNs (0.3, 0.5, 0.9). For a 6-DOF couch, these margins were as follows:
      prostate (0.2, 0.6, 0.8), SV (0.3, 0.9, 1.0), and LNs (0.3, 0.4, 0.3) for bone
      guidance. For prostate guidance, margins were as follows: prostate (0, 0, 0), SV
      (0.2, 0.5, 0.4), and LNs (0.3, 0.6, 0.6). CONCLUSIONS: Image guided radiation
      therapy based on bony anatomy requires larger prostate and SV margins, and
      guidance on prostate requires larger LN margins. Neither guidance strategy is
      optimal, and a combination of the 2 or treatment adaptation after a number of
      fractions might be preferable. Calculation of the total margin should also
      include delineation uncertainties.

PMID- 29051039
TI  - Convolvulus pluricaulis (Shankhapushpi) ameliorates human microtubule-associated
      protein tau (hMAPtau) induced neurotoxicity in Alzheimer's disease Drosophila
      model.
AB  - Convolvulus pluricaulis (Shankhapushpi) has long been used as traditional herbal
      medicine in India as nerve tonic. We studied the neuroprotective effects of C.
      pluricaulis extract (aqueous) against human microtubule-associated protein tau
      (hMAPtau) induced neurotoxicity in Alzheimer's disease (AD) Drosophila model. We
      analysed the lifespan, locomotor activity, tau protein level, reactive oxygen
      species (ROS), lipid peroxidation (LPO), catalase (CAT), superoxide dismutase
      (SOD) and acetylcholinesterase (AChE) activities in 10th, 20th and 30th days old
      control (wild type), tau control tauopathy Drosophila reared on C. pluricaulis
      supplemented with regular food or regular standard food. C. pluricaulis
      significantly offsets hMAPtau induced early death and extends the lifespan and
      diminishes the level of tau protein in tauopathy Drosophila. C. pluricaulis also
      enhances the antioxidant enzyme activities and ameliorates the tau-induced
      oxidative stress and restore the depleted AChE activity in the fly model. This
      study provides the first evidence that supplementation of C. pluricaulis along
      with the regular standard food ameliorate the neurotoxic effect of hMAPtau in AD
      Drosophila model and also reveals that it is a potent neuroprotective agent.

PMID- 29051037
TI  - Serum MicroRNA Signature Predicts Response to High-Dose Radiation Therapy in
      Locally Advanced Non-Small Cell Lung Cancer.
AB  - PURPOSE: To assess the utility of circulating serum microRNAs (c-miRNAs) to
      predict response to high-dose radiation therapy for locally advanced non-small
      cell lung cancer (NSCLC). METHODS AND MATERIALS: Data from 80 patients treated
      from 2004 to 2013 with definitive standard- or high-dose radiation therapy for
      stages II-III NSCLC as part of 4 prospective institutional clinical trials were
      evaluated. Pretreatment serum levels of 62 miRNAs were measured by quantitative
      reverse transcription-polymerase chain reaction array. We combined miRNA data and
      clinical factors to generate a dose-response score (DRS) for predicting overall
      survival (OS) after high-dose versus standard-dose radiation therapy. Elastic net
      Cox regression was used for variable selection and parameter estimation. Model
      assessment and tuning parameter selection were performed through full cross
      validation. The DRS was also correlated with local progression, distant
      metastasis, and grade 3 or higher cardiac toxicity using Cox regression, and
      grade 2 or higher esophageal and pulmonary toxicity using logistic regression.
      RESULTS: Eleven predictive miRNAs were combined with clinical factors to generate
      a DRS for each patient. In patients with low DRS, high-dose radiation therapy was
      associated with significantly improved OS compared to treatment with standard
      dose radiation therapy (hazard ratio 0.22). In these patients, high-dose
      radiation also conferred lower risk of distant metastasis and local progression,
      although the latter association was not statistically significant. Patients with
      high DRS exhibited similar rates of OS regardless of dose (hazard ratio 0.78).
      The DRS did not correlate with treatment-related toxicity. CONCLUSIONS: Using c
      miRNA signature and clinical factors, we developed a DRS that identified a subset
      of patients with locally advanced NSCLC who derive an OS benefit from high-dose
      radiation therapy. This DRS may guide dose escalation in a patient-specific
      manner.

PMID- 29051040
TI  - On the Potential Role of MRI Biomarkers of COPD to Guide Bronchoscopic Lung
      Volume Reduction.
AB  - RATIONALE AND OBJECTIVES: In patients with severe emphysema and poor quality of
      life, bronchoscopic lung volume reduction (BLVR) may be considered and guided
      based on lobar emphysema severity. In particular, x-ray computed tomography (CT)
      emphysema measurements are used to identify the most diseased and the second-most
      diseased lobes as BLVR targets. Inhaled gas magnetic resonance imaging (MRI) also
      provides chronic obstructive pulmonary disease (COPD) biomarkers of lobar
      emphysema and ventilation abnormalities. Our objective was to retrospectively
      evaluate CT and MRI biomarkers of lobar emphysema and ventilation in patients
      with COPD eligible for BLVR. We hypothesized that MRI would provide complementary
      biomarkers of emphysema and ventilation that help determine the most appropriate
      lung lobar targets for BLVR in patients with COPD. MATERIALS AND METHODS: We
      retrospectively evaluated 22 BLVR-eligible patients from the Thoracic Imaging
      Network of Canada cohort (diffusing capacity of the lung for carbon monoxide = 37
      +/- 12%predicted, forced expiratory volume in 1 second = 34 +/- 7%predicted,
      total lung capacity = 131 +/- 17%predicted, and residual volume = 216 +/-
      36%predicted). Lobar CT emphysema, measured using a relative area of <-950
      Hounsfield units (RA950) and MRI ventilation defect percent, was independently
      used to rank lung lobe disease severity. RESULTS: In 7 of 22 patients, there were
      different CT and MRI predictions of the most diseased lobe. In some patients,
      there were large ventilation defects in lobes not targeted by CT, indicative of a
      poorly ventilated lung. CT and MRI classification of the most diseased and the
      second-most diseased lobes showed a fair-to-moderate intermethod reliability
      (Cohen kappa = 0.40-0.59). CONCLUSIONS: In this proof-of-concept retrospective
      analysis, quantitative MRI ventilation and CT emphysema measurements provided
      different BLVR targets in over 30% of the patients. The presence of large MRI
      ventilation defects in lobes next to CT-targeted lobes might also change the
      decision to proceed or to guide BLVR to a different lobar target.

PMID- 29051041
TI  - Retinal vasculature and 5-year metabolic syndrome among women with gestational
      diabetes mellitus.
AB  - BACKGROUND: Women with gestational diabetes mellitus (GDM) are at greater risk of
      metabolic syndrome (MetS). We studied the association between second-trimester
      retinal microvasculature and 5-year MetS incidence in women with GDM. METHODS: A
      total of 142 mothers with GDM were recruited and followed up 5years after
      delivery. Retinal photography was performed at 26-28weeks gestation and metabolic
      outcomes were assessed at the 5-year postpartum follow-up visit. GDM and MetS
      were defined based on World Health Organization (WHO) guidelines and Adults
      Treatment Panel (ATP) III guidelines, respectively. Modified-Poisson regression
      was applied to study the association between second-trimester retinal
      microvasculature and incident 5-year maternal MetS, after adjusting for major
      confounders. Area under the curve (AUC) was calculated based on the final model.
      RESULTS: Our prospective cohort reported a 9.2% incidence rate of 5-year MetS
      among women with GDM. After adjusting for maternal age, ethnicity, college
      degree, pre-pregnancy BMI and fasting glucose at 26-28week gestation, each 10MUm
      widening in retinal venular caliber was associated with an increased relative
      risk of 1.6 (95% confidence interval [CI]: 1.0, 2.8) in incident MetS. In
      addition to traditional risks of pre-pregnancy BMI and fasting glucose level at
      26-28week gestation, retinal venular caliber mildly increased the prediction of 5
      year maternal MetS by 1.8%. CONCLUSIONS: Second-trimester retinal venular
      widening was associated with incident 5-year maternal MetS in women with GDM. Our
      study suggests that mother with GDM at risk of future MetS development may have
      already presented retinal microvascular abnormalities during pregnancy.

PMID- 29051042
TI  - Bone disease in primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT) is a disease of high bone turnover, decreased
      bone mineral density (BMD) especially at cortical sites, and increased risk of
      fractures at all skeletal sites. Early diagnosis during the last decades resulted
      in milder forms of bone involvement. New methods of imaging and validation such
      as high resolution peripheral quantitative computed tomography and trabecular
      bone score provide evidence of disturbed bone microarchitecture and explain
      further the increased risk of fractures at both cortical and trabecular skeletal
      sites. Parathyroidectomy has a long-term beneficial effect on the skeleton and is
      probably prudent to refer PHPT patients for surgery in all cases where increased
      bone fragility is suspected. Bisphosphonates (BPs), mainly alendronate, have been
      proved as reasonable choices for BMD improvement while cinacalcet has no effect
      on bone strength in PHPT. Combination of BPs and cinacalcet, is a valid
      therapeutic approach from a pathophysiological point of view at least in terms of
      bone health, however, an adequately powered study to prove it is lacking.
      Adequate dietary calcium intake and vitamin D supplementation is advised as in
      the general population for the skeletal integrity of PHPT patients albeit with a
      close monitoring of serum and urinary calcium levels.

PMID- 29051043
TI  - Lysyl oxidase and adipose tissue dysfunction.
AB  - BACKGROUND/OBJECTIVES: Lysyl oxidase (LOX) is an enzyme crucial for collagen
      fibre crosslinking and thus for fibrosis development. Fibrosis is characterised
      by a surplus of collagen fibre accumulation and is amongst others also a feature
      of obesity-associated dysfunctional adipose tissue (AT) which has been linked
      with type 2 diabetes. We hypothesised that in type 2 diabetes and obesity LOX
      expression and activity will be increased as a consequence of worsening AT
      dysfunction. This study aimed to provide a comprehensive characterisation of LOX
      in human AT. METHODS: LOX mRNA expression was analysed in omental and abdominal
      subcutaneous AT obtained during elective surgery from subjects with a wide range
      of BMI, with and without diabetes. In addition, LOX expression was studied in
      subcutaneous AT before and 9.5months after bariatric surgery. To study the
      mechanism of LOX changes, its expression and activity were assessed after either
      hypoxia, recombinant human leptin or glucose treatment of AT explants. In
      addition, LOX response to acute inflammation was tested after stimulation by a
      single injection of lipopolysaccharide versus saline solution (control) in
      healthy men, in vivo. Quantity of mRNA was measured by RT-qPCR. RESULTS: LOX
      expression was higher in obesity and correlated with BMI whilst, in vitro, leptin
      at high concentrations, as a potential feedback mechanism, suppressed its
      expression. Neither diabetes status, nor hyperglycaemia affected LOX. Hypoxia and
      lipopolysaccharide-induced acute inflammation increased LOX AT expression, latter
      was independent of macrophage infiltration. CONCLUSIONS: Whilst LOX may not be
      affected by obesity-associated complications such as diabetes, our results
      confirm that LOX is increased by hypoxia and inflammation as underlying mechanism
      for its upregulation in adipose tissue with obesity.

PMID- 29051044
TI  - The effect of health on socioeconomic status: Using instrumental variables to
      revisit a successful randomized controlled trial.
AB  - Poor health is widely recognized as a consequence of social disadvantage, but
      health problems may also help transmit social disadvantage over time and
      generations. Experimentally assigned health exposures, namely those tested in
      randomized controlled trials, may provide opportunities to estimate the causal
      effects of health on socioeconomic status (SES). We revisit data from the
      Diabetes Control and Complications Trial, a randomized controlled trial of
      glucose control therapy in Type 1 diabetic patients, and use treatment assignment
      as an instrument for health status to test the causal effect of treatment-related
      health improvement on subsequent SES measured during the trial's follow-up study,
      the Epidemiology of Diabetes Interventions and Complications study. We used the
      Two-Factor Hollingshead Index of Social Position, which comprises education and
      occupation, to measure SES. Glycated hemoglobin (HbA1c) served as a proxy for
      health status. Ordinary least squares (OLS) regression models showed that lower
      HbA1c at the trial's end was associated with higher SES at both the start of the
      follow-up and 17 years later. However, instrumental variable analyses showed no
      causal effect of HbA1c on SES, suggesting that OLS estimates are biased by
      endogeneity. Sensitivity analyses showed robustness to several alternate
      specifications. While the HbA1c advantage conferred by random assignment to
      treatment within the trial did not produce higher Hollingshead Index scores, we
      note that occupation and education categories may be harder to affect than are
      outcomes such as income. This analysis offers evidence that clinical trial data
      may be a rich and unrecognized resource for estimating health effects on SES.

PMID- 29051045
TI  - Angiotensin II regulates delta-ENaC in human umbilical vein endothelial cells.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) has been characterized
      in a variety of non-epithelial tissues. In the current study we sought to
      understand the effect of angiotensin II on delta ENaC function using human
      umbilical vein endothelial cells (HUVECs). The delta ENaC subunit is found in
      humans, but notably absent in rat and most mouse epithelial tissues. In this
      study we report the presence of delta ENaC in HUVECS with a half-life of ~80min
      and a change in delta ENaC abundance when HUVECs were treated with angiotensin
      II. We also observed that angiotensin II increased apical membrane expression of
      delta ENaC and decreased protein ubiquitination. Equivalent short circuit current
      measurements showed angiotensin II increased delta ENaC ion transport in HUVEC
      cells. Treatment with the antioxidant apocynin attenuated angiotensin II mediated
      effects indicating an important role for angiotensin-derived H2O2 in delta ENaC
      subunit regulation. Whole cell recordings from oocytes injected with
      deltabetagamma ENaC shows H2O2-sensitive current. These results suggest that
      delta ENaC subunits can make up functional channel in HUVEC cells that are
      regulated by angiotensin II in a redox-sensitive manner. The novel findings have
      significant implications for our understanding of the role of ENaC in vascular
      conditions in which oxidative stress occurs.

PMID- 29051046
TI  - Fungal glucuronoyl esterases: Genome mining based enzyme discovery and
      biochemical characterization.
AB  - 4-O-Methyl-d-glucuronic acid (MeGlcA) is a side-residue of glucuronoarabinoxylan
      and can form ester linkages to lignin, contributing significantly to the strength
      and rigidity of the plant cell wall. Glucuronoyl esterases (4-O-methyl
      glucuronoyl methylesterases, GEs) can cleave this ester bond, and therefore may
      play a significant role as auxiliary enzymes in biomass saccharification for the
      production of biofuels and biochemicals. GEs belong to a relatively new family of
      carbohydrate esterases (CE15) in the CAZy database (www.cazy.org), and so far
      around ten fungal GEs have been characterized. To explore additional GE enzymes,
      we used a genome mining strategy. BLAST analysis with characterized GEs against
      approximately 250 publicly accessible fungal genomes identified more than 150
      putative fungal GEs, which were classified into eight phylogenetic sub-groups. To
      validate the genome mining strategy, 21 selected GEs from both ascomycete and
      basidiomycete fungi were heterologously produced in Pichia pastoris. Of these
      enzymes, 18 were active against benzyl d-glucuronate demonstrating the
      suitability of our genome mining strategy for enzyme discovery.

PMID- 29051048
TI  - Reconstruction of soft tissue defects of the distal third of the arm using a
      muscle-sparing latissimus dorsi musculocutaneous flap.
AB  - Use of a latissimus dorsi (LD) flap has been widely described for upper limb
      reconstruction. However, donor site sequelae have led to the development of
      muscle-sparing techniques for the LD flap. We present the technical principles of
      a muscle-sparing LD flap and its use as a pedicled flap to reconstruct the distal
      third of the arm.

PMID- 29051047
TI  - Ostomy telehealth for cancer survivors: Design of the Ostomy Self-management
      Training (OSMT) randomized trial.
AB  - PURPOSE: An ostomy adversely affects health-related quality of life (HRQOL) in a
      diverse population of cancer survivors and their caregivers. Hit-or-miss ostomy
      care, nurse counseling, and community referral have been the primary modes of
      self-management education and support in the peri-operative setting. Few evidence
      based, systematic ostomy self-management programs are available to ensure optimal
      post-operative care. This paper describes the study design of a telehealth-based
      Ostomy Self-management Training (OSMT) program for cancer survivors and their
      caregivers. METHODS: The study is a three-year, randomized trial that tests the
      effectiveness of the OSMT program on survivor activation, self-efficacy, and
      HRQOL. The intervention integrates goal setting and problem-solving approaches to
      enhance survivor activation and self-efficacy to carry out ostomy care. The
      curriculum is delivered via four group sessions administered by trained ostomy
      certified nurses (WOCNs) and peer ostomates. An additional session is offered to
      caregivers to address their needs in relation to ostomy care. Telehealth
      approaches through videoconferencing are used to enhance program delivery to
      participants in three different geographic areas across two time zones.
      Participants join sessions via real-time videoconferencing from their homes.
      CONCLUSIONS: The OSMT program has high potential to make a positive impact on the
      unique physical, psychological, social, and spiritual needs of cancer survivors
      living with a permanent ostomy. The study design, process, and telehealth
      approach contributes to the success of future dissemination efforts of the
      intervention into diverse clinical and community settings.

PMID- 29051049
TI  - Which surgery should be offered for carpal tunnel syndrome in a patient who was
      previously treated for recurrence on the contralateral side? Preliminary study of
      13 patients with the Canaletto(r) implant.
AB  - There are no published studies on the management of carpal tunnel syndrome (CTS)
      patients who have already been operated for recurrent CTS on the contralateral
      side. The aim of this study was to evaluate 13 patients with CTS who underwent
      primary release using a Canaletto(r) implant. The 13 patients had all been
      operated for recurrent CTS previously. On the contralateral side, they all had
      subjective signs, and two of them already had complications. All were operated
      with the Canaletto(r) implant according to Duche's technique, in a mean of
      20minutes. After a mean 19.3-month follow-up, paresthesia, pain, and QuickDASH
      scores were significantly improved, even in one patient who underwent revision at
      another facility. This preliminary study suggests that use of a Canaletto(r)
      implant as first-line treatment for CTS in patients who already underwent
      revision surgery on the other side is a simple and safe technique, without
      worsening of symptoms. These findings should be assessed with a prospective
      randomized controlled trial.

PMID- 29051050
TI  - Intramuscular hemangioma of the hypothenar eminence. A case report.
AB  - Intramuscular hemangiomas are benign vascular tumors. They develop in striated
      muscles. Various sites have been reported in the literature but only rarely in
      the hand. We report on a case of an intramuscular hemangioma located within the
      hypothenar eminence, diagnosed by a biopsy. Treatment options are limited in the
      hand as embolization may lead to a risk of digital ischemia and sclerotherapy may
      lead to recurrence. This type of infiltrating tumor is poorly structured within
      the muscle, thus simple removal is not an option. Surgical excision of the entire
      affected muscle, in our case the abductor digiti minimi, was performed without
      any consequences on the hand's function and no signs of recurrence at the latest
      follow-up of 6months.

PMID- 29051051
TI  - Brief introduction of current technologies in isolation of broadly neutralizing
      HIV-1 antibodies.
AB  - HIV/AIDS has become a worldwide pandemic. Before an effective HIV-1 vaccine
      eliciting broadly neutralizing monoclonal antibodies (bnmAbs) is fully developed,
      passive immunization for prevention and treatment of HIV-1 infection may
      alleviate the burden caused by the pandemic. Among HIV-1 infected individuals,
      about 20% of them generated cross-reactive neutralizing antibodies two to four
      years after infection, the details of which could provide knowledge for effective
      vaccine design. Recent progress in techniques for isolation of human broadly
      neutralizing antibodies has facilitated the study of passive immunization. The
      isolation and characterization of large panels of potent human broadly
      neutralizing antibodies has revealed new insights into the principles of antibody
      mediated neutralization of HIV. In this paper, we review the current effective
      techniques in broadly neutralizing antibody isolation.

PMID- 29051052
TI  - Pea early-browning virus-mediated genome editing via the CRISPR/Cas9 system in
      Nicotiana benthamiana and Arabidopsis.
AB  - The clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR
      associated (Cas9) system has enabled efficient genome engineering in diverse
      plant species. However, delivery of genome engineering reagents, such as the
      single guide RNA (sgRNA), into plant cells remains challenging. Here, we report
      the engineering of Tobacco rattle virus (TRV) and Pea early browning virus (PEBV)
      to deliver one or multiple sgRNAs into Nicotiana benthamiana and Arabidopsis
      thaliana (Col-0) plants that overexpress a nuclear localization signal containing
      Cas9. Our data showed that TRV and PEBV can deliver sgRNAs into inoculated and
      systemic leaves, and this resulted in mutagenesis of the targeted genomic loci.
      Moreover, in N. benthamiana, PEBV-based sgRNA delivery resulted in more targeted
      mutations than TRV-based delivery. Our data indicate that TRV and PEBV can
      facilitate plant genome engineering and can be used to produce targeted mutations
      for functional analysis and other biotechnological applications across diverse
      plant species. Key message: Delivery of genome engineering reagents into plant
      cells is challenging and inefficient and this limit the applications of this
      technology in many plant species. RNA viruses such as TRV and PEBV provide an
      efficient tool to systemically deliver sgRNAs for targeted genome modification.

PMID- 29051054
TI  - Gene-environment interaction and psychiatric disorders: Review and future
      directions.
AB  - Empirical studies suggest that psychiatric disorders result from a complex
      interplay between genetic and environmental factors. Most evidence for such gene
      environment interaction (GxE) is based on single candidate gene studies conducted
      from a Diathesis-Stress perspective. Recognizing the short-comings of candidate
      gene studies, GxE research has begun to focus on genome-wide and polygenic
      approaches as well as drawing on different theoretical concepts underlying GxE,
      such as Differential Susceptibility. After reviewing evidence from candidate GxE
      studies and presenting alternative theoretical frameworks underpinning GxE
      research, more recent approaches and findings from whole genome approaches are
      presented. Finally, we suggest how future GxE studies may unpick the complex
      interplay between genes and environments in psychiatric disorders.

PMID- 29051053
TI  - Milk lipid regulation at the maternal-offspring interface.
AB  - Milk lipids provide a large proportion of energy, nutrients, essential fatty
      acids, and signaling molecules for the newborns, the synthesis of which is a
      tightly controlled process. Dysregulated milk lipid production and composition
      may be detrimental to the growth, development, health and survival of the
      newborns. Many genetically modified animal models have contributed to our
      understanding of milk lipid regulation in the lactating mammary gland. In this
      review, we discuss recent advances in our knowledge of the mechanisms that
      control milk lipid biosynthesis and secretion during lactation, and how maternal
      genetic and dietary defects impact milk lipid composition and consequently
      offspring traits.

PMID- 29051055
TI  - Skeletal impairment in Pierson syndrome: Is there a role for lamininbeta2 in bone
      physiology?
AB  - INTRODUCTION: Pierson syndrome is caused by a mutation of LAMB2, encoding for
      laminin beta2. Clinical phenotype is variable but usually associates congenital
      nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has
      also been described. METHODS: We report on a 15-year old girl, suffering from
      Pierson Syndrome, who developed severe bone deformations during puberty. This
      patient initially displayed CNS and microcoria, leading to the clinical diagnosis
      of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice
      site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at
      the age of 3. After R-Tx, renal evolution was simple, the patient receiving low
      dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12,
      bone deformations progressively appeared. At the time of bone impairment, renal
      function was subnormal (glomerular filtration rate using iohexol clearance
      50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal
      (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D
      73nmol/L). Radiographs showed major deformations such as scoliosis, genu varum
      and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was
      performed, demonstrating a bone of "normal low" quantity and quality; major
      radial and cubital deformations were observed. Stainings of laminin beta2 were
      performed on bone and renal samples from the patient and healthy controls: as
      expected, laminin beta2 was expressed in the control kidney but not in the
      patient's renal tissue, and a similar pattern was observed in bone. CONCLUSION:
      This is the first case of skeletal impairment ever described in Pierson syndrome.
      Integrin alpha3beta1, receptor for laminin beta2, are found in podocytes and
      osteoblasts, and the observation of both the presence of laminin beta2 staining
      in healthy bone and its absence in the patient's bone raises the question of a
      potential role of laminin beta2 in bone physiology.

PMID- 29051056
TI  - Recovery of Serum Testosterone Levels and Sexual Function in Patients Treated
      With Short-term Luteinizing Hormone-releasing Hormone Antagonist as a Neoadjuvant
      Therapy Before External Radiotherapy for Intermediate-risk Prostate Cancer:
      Preliminary Prospective Study.
AB  - INTRODUCTION: External beam radiation therapy (EBRT) with short-term androgen
      deprivation therapy is the standard of care for intermediate-risk prostate cancer
      patients. However, no study to date has evaluated the hormonal kinetics or sexual
      and hormonal function recovery after cessation of short-term luteinizing hormone
      (LH)-releasing hormone (LHRH) antagonist treatment. PATIENTS AND METHODS: Ten
      intermediate-risk prostate cancer patients (mean age, 69.9 years) were included.
      All patients received 4 months of LHRH antagonist (degarelix) treatment followed
      by EBRT. The testosterone, luteinizing hormone (LH), follicle-stimulating
      hormone, and prostate-specific antigen levels were measured and Expanded Prostate
      Cancer Index Composite questionnaires were completed before LHRH antagonist
      therapy at baseline; 1, 2, 3, and 4 months after the first injection of LHRH
      antagonist treatment; and every 2 months thereafter until 18 months. RESULTS: The
      testosterone levels were at the castration level at 1 month after the first LHRH
      antagonist injection. The median interval to recover a normal testosterone level
      (> 7.2 nmol/L) was 7 months after the last LHRH antagonist administration. The LH
      and follicle-stimulating hormone levels decreased but had increased more than
      twice above baseline at 15 months after the last LHRH antagonist injection. The
      sexual function and hormonal bother subdomain scores and sexual and hormonal
      domain scores decreased once after LHRH antagonist treatment but had
      significantly recovered thereafter (P < .05). CONCLUSION: In most patients, the
      testosterone level had normalized within 9 months after the last LHRH
      administration. Sexual and hormonal function recovered after short-term LHRH
      antagonist administration for neoadjuvant therapy before EBRT.

PMID- 29051057
TI  - Mannheimia haemolytica A2 secretes different proteases into the culture medium
      and in outer membrane vesicles.
AB  - Respiratory diseases in ruminants have a significantly negative impact on the
      worldwide economy. The bacterium Mannheimia haemolytica is involved in pneumonic
      infections in bovine and ovine. In gram-negative bacteria, six secretion systems
      related to the colonization process and host tissue damage have been reported. In
      addition, in the last two decades, the production of outer membrane vesicles has
      been studied as a different bacterial strategy to release virulence factors, such
      as exotoxins, lipopolysaccharides, and proteases. However, in M. haemolytica
      serotype A2, protease secretion and release in vesicles have not been reported as
      virulence mechanisms. The aim of this work was to identify proteases released
      into the culture supernatant and in vesicles of M. haemolytica A2. Our results
      showed evident differences in the molecular mass and activity of proteases
      present in culture supernatants and outer membrane vesicles based on zymography
      assays. The biochemical characterization of M. haemolytica proteases revealed
      that the main types were cysteine and metalloproteases. A specific
      metalloprotease of 100 kDa was active in the culture supernatants, but it was not
      active and was found in low quantities in vesicles. Proteases could be an
      important virulence factor during the infectious pneumonic process led by M.
      haemolytica.

PMID- 29051058
TI  - Cytomegalovirus infection in pregnant women and its association with bad
      obstetric outcomes in Northern India.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection during pregnancy is far more complex
      than other infections, due to ability of the virus to be frequently reactivated
      during the child bearing age and may vertically transmitted to the developing
      fetus in spite of maternal immunity. Therefore, in the current study we
      determined the prevalence of CMV infection in pregnant women and tried to
      identify the role of maternal CMV infection in adverse pregnancy outcomes in
      Northern India. In this case-control study, 517 pregnant women, out of them 200
      in case group and 317 in the control group. The overall 31.72% (164/517) cases
      were found with active CMV infection. CMV positivity (p=0.026) was significantly
      associated with bad obstetric history (75/200, 37.50%) compared to normal
      pregnancy (89/317, 28.07%). CMV infection was predominantly observed in age group
      21-25 years. CMV positivity have been found to be significantly higher in women
      from rural area as compare to those from urban area (p=0.028). However, no
      significant difference has been observed in case of occupation, income, and
      haemoglobin level.

PMID- 29051059
TI  - First report of the Staphylococcus aureus isolate from subclinical bovine
      mastitis in the South of Brazil harboring resistance gene dfrG and transposon
      family Tn916-1545.
AB  - The aim of this work was to identify at the molecular level the species of
      coagulase-positive staphylococci isolates from clinical and subclinical bovine
      mastitis samples in Southern Brazil, and to evaluate the antimicrobial resistance
      profile, as well as the presence of resistance genes. According to the PCR assay,
      all 31 isolates were classified as Staphylococcus aureus. The isolates were
      tested for resistance to penicillin, ampicillin, oxacillin, cefoxitin,
      cephalothin, ceftiofur, streptomycin, tobramycin, teicoplanin, erythromycin,
      clindamycin, enrofloxacin, sulfonamide, trimethoprim-sulfamethoxazole,
      trimethoprim, and tetracycline by the disk diffusion method. Most of the isolates
      were resistant to sulfonamide (20), followed by ampicillin and clindamycin (16).
      Twenty isolates were multidrug-resistant. PCR was used for the detection of
      several antimicrobial resistance genes (ereB, ermB, ermC, tetA, tetB, tetK, tetL,
      tetM, tetO, Tn916-1545, strA, strB, sul1, sul2, dfrA, dfrG, dfrK, blaZ, mecA, and
      mecC). The most prevalent antimicrobial resistance genes were tetK and tetL,
      ereB, followed by tetM, Tn916-1545 and blaZ, detected in 11, nine and four
      isolates, respectively. For all the tetM gene positive isolates, the presence of
      conjugative transposons of the Tn916-1545 family was detected. The presence of
      multidrug-resistant isolates, antimicrobial resistance genes and transposons
      suggests a potential risk of spreading multi-resistance genes to other bacteria.

PMID- 29051060
TI  - Treatment with 3'-deoxyadenosine and deoxycoformycin in mice infected by
      Trypanosoma cruzi and its side effect on purinergic enzymes.
AB  - The aim of this study was to evaluate the efficacy of 3'-deoxyadenosine and
      deoxycoformycin combination in the treatment of mice infected by T. cruzi, as
      well as to verify the influence of the treatment on purinergic enzymes. Heart and
      serum samples were collected from 60 mice (30 infected and 30 uninfected) at day
      12 post-infection. To verify treatment efficacy, parasitemia was monitored, and
      the treatment with 3'-deoxy adenosine and deoxycoformycin combination was able to
      reduce it, but had no curative effect on mice. Seric activities of NTPDase (ATP
      and ADP substrate) and ADA were increased significantly in untreated mice
      infected by T. cruzi compared to the negative control, as well as mice treated
      with 3'-deoxyadenosine and deoxycoformycin (alone or combined) modulated the
      activity of NTPDase (ATP and ADP substrate), preventing them from increasing in
      infected animals (activity similar to healthy animals). Treatment with
      deoxycoformycin alone and associated with 3'-deoxyadenosine modulated the
      activity of ADA preventing them from increasing in infected animals. However,
      seric activities of ADA in mice treated with 3'-deoxyadenosine (cordycepin) alone
      does not modify the ADA activity compared with infected and non-treated mice.
      However, the 5'-nucleotidase activity decreased significantly in infected
      untreated animals and the same occurred in infected and treated animals with
      deoxycoformycin and 3'-deoxyadenosine. However, treatment with deoxycoformycin
      associated with 3'-deoxyadenosine preventing them from decreasing the 5'
      nucleotidase activity. Therefore, we conclude that the treatments did not have
      curative success for mice infected by T. cruzi. However, the treatments were able
      to modulate the purinergic enzymes during the infection by T. cruzi, which may
      contribute to reduce the inflammatory damage in heart.

PMID- 29051061
TI  - Precise laser poration to control drug delivery into and through human nail.
AB  - Drug treatment of diseases of the human nail remains a difficult challenge;
      topical therapy, in particular, is limited by very poor transport of active
      agents across the nail itself. The objective of this research was to examine the
      potential of controlled, and fibre-optic delivered, femtosecond laser light
      pulses to provide new pathways and opportunities for drug access to targets
      within and beneath the nail plate. Optical, confocal fluorescence and scanning
      electron microscopies demonstrated partial and complete laser poration of human
      nail samples, with the energy per pore and the exposure duration being the key
      modulating parameters that determined the extent of ablation achieved. Parallel
      measurements of the penetration of a model drug across laser-treated nails showed
      that complete poration resulted in essentially complete circumvention of the
      diffusion barrier, an array of 100 pores in 0.2cm2 area of nail permitting a 103
      fold increase in initial drug uptake. Partial ablation of the nail created pores
      that extended to a range of depths; the nail material adjacent to the ablated
      area was rendered porous in appearance presumably due to local thermal
      perturbation of the nail structure. These openings offer, as a result, potential
      sites in which topical drug formulations might be sequestered post-poration and
      from which slow, sustained delivery of the active agent into and through the nail
      may be envisaged.

PMID- 29051062
TI  - New molecular targets for functionalized nanosized drug delivery systems in
      personalized therapy for hepatocellular carcinoma.

PMID- 29051063
TI  - Defining optimal permeant characteristics for ultrasound-mediated
      gastrointestinal delivery.
AB  - Ultrasound-mediated drug delivery in the gastrointestinal (GI) tract is a
      bourgeoning area of study. Localized, low-frequency ultrasound has recently been
      shown to enable significant enhancement in delivery of a broad set of active
      pharmaceutical ingredients including small molecules, proteins, and nucleic acids
      without any formulation or encapsulation of the therapeutic. Traditional chemical
      formulations are typically required to protect, stabilize, and enable the
      successful delivery of a given therapeutic. The use of ultrasound, however, may
      make delivery insensitive to the chemical formulation. This might open the door
      to chemical formulations being developed to address other properties besides the
      deliverability of a therapeutic. Instead, chemical formulations could potentially
      be developed to achieve novel pharmacokinetics, without consideration of that
      particular formulation's ability to penetrate the mucus barrier passively. Here
      we investigated the effect of permeant size, charge, and the presence of chemical
      penetration enhancers on delivery to GI tissue using ultrasound. Short ultrasound
      treatments enabled delivery of large permeants, including microparticles, deep
      into colonic tissue ex vivo. Delivery was relatively independent of size and
      charge but did depend on conformation, with regular, spherical particles being
      delivered to a greater extent than long-chain polymers. The subsequent residence
      time of model permeants in tissue after ultrasound-mediated delivery was found to
      depend on size, with large microparticles demonstrating negligible clearance from
      the local tissue 24h after delivery ex vivo. The dependence of clearance time on
      permeant size was further confirmed in vivo in mice using fluorescently labeled
      3kDa and 70kDa dextran. The use of low-frequency ultrasound in the GI tract
      represents a novel tool for the delivery of a wide-range of therapeutics
      independent of formulation, potentially allowing for the tailoring of
      formulations to impart novel pharmacokinetic profiles once delivered into tissue.

PMID- 29051064
TI  - Harnessing the cross-talk between tumor cells and tumor-associated macrophages
      with a nano-drug for modulation of glioblastoma immune microenvironment.
AB  - Glioblastoma (GBM) is the most frequent and malignant brain tumor with a high
      mortality rate. The presence of a large population of macrophages (Mphi) in the
      tumor microenvironment is a prominent feature of GBM and these so-called tumor
      associated Mphi (TAM) closely interact with the GBM cells to promote the
      survival, progression and therapy resistance of the GBM. Various therapeutic
      strategies have been devised either targeting the GBM cells or the TAM but few
      have addressed the cross-talks between the two cell populations. The present
      study was carried out to explore the possibility of exploiting the cross-talks
      between the GBM cells (GC) and TAM for modulation of the GBM microenvironment
      through using Nano-DOX, a drug composite based on nanodiamonds bearing
      doxorubicin. In the in vitro work on human cell models, Nano-DOX-loaded TAM were
      first shown to be viable and able to infiltrate three-dimensional GC spheroids
      and release cargo drug therein. GC were then demonstrated to encourage Nano-DOX
      loaded TAM to unload Nano-DOX back into GC which consequently emitted damage
      associated molecular patterns (DAMPs) that are powerful immunostimulatory agents
      as well as indicators of cell damage. Nano-DOX was next proven to be a more
      potent inducer of GC DAMPs emission than doxorubicin. As a result, Nano-DOX
      damaged GC exhibited an enhanced ability to attract both TAM and Nano-DOX-loaded
      TAM. Most remarkably, Nano-DOX-damaged GC reprogrammed the TAM from a pro-GBM
      phenotype to an anti-GBM phenotype that suppressed GC growth. Finally, the in
      vivo relevance of the in vitro findings was tested in animal study. Mice bearing
      orthotopic human GBM xenografts were intravenously injected with Nano-DOX-loaded
      mouse TAM which were found releasing drug in the GBM xenografts 24h after
      injection. GC damage was evidenced by the induction of DAMPs emission within the
      xenografts and a shift of TAM phenotype was detected as well. Taken together, our
      results demonstrate a novel way with therapeutic potential to harness the cross
      talk between GBM cells and TAM for modulation of the tumor immune
      microenvironment.

PMID- 29051065
TI  - Dihydroergotamine mesylate-loaded dissolving microneedle patch made of
      polyvinylpyrrolidone for management of acute migraine therapy.
AB  - Migraine is a widespread neurological disease with negative effects on quality of
      life and productivity. Moderate to severe acute migraine attacks can be treated
      with dihydroergotamine mesylate (DHE), an ergot derivative that is especially
      effective in non-responders to triptan derivatives. To overcome limitations of
      current DHE formulations in subcutaneous injection and nasal spray such as pain,
      adverse side effects and poor bioavailability, a new approach is needed for DHE
      delivery enabling painless self-administration, quick onset of action, and high
      bioavailability. In this study, we developed a dissolving microneedle patch (MNP)
      made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility
      enhancement properties, using a MNP design previously shown to be painless and
      simple to administer. DHE-loaded MNPs were shown to have a content uniformity of
      108+/-9% with sufficient mechanical strength for insertion to pig skin ex vivo
      and dissolution within 2min. In vivo pharmacokinetic studies were carried out on
      hairless rats, and DHE plasma levels were determined by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE
      delivery by MNP (1259+/-917ng/mL min) was not significantly different (p>0.05) as
      compared to subcutaneous injection, with a relative bioavailability of 97%. Also,
      appreciable plasma levels of DHE were seen within 5min for both delivery methods
      and tmax value of MNPs (38+/-23min) showed no significant difference (p>0.05)
      compared to subcutaneous injection (24+/-13min). These results suggest that DHE
      loaded MNPs have promise as an alternative DHE delivery method that can be
      painlessly self-administered with rapid onset and high bioavailability.

PMID- 29051066
TI  - Study of the Cys-His bridge electron transfer pathway in a copper-containing
      nitrite reductase by site-directed mutagenesis, spectroscopic, and computational
      methods.
AB  - The Cys-His bridge as electron transfer conduit in the enzymatic catalysis of
      nitrite to nitric oxide by nitrite reductase from Sinorhizobium meliloti 2011
      (SmNir) was evaluated by site-directed mutagenesis, steady state kinetic studies,
      UV-vis and EPR spectroscopic measurements as well as computational calculations.
      The kinetic, structural and spectroscopic properties of the His171Asp (H171D) and
      Cys172Asp (C172D) SmNir variants were compared with the wild type enzyme.
      Molecular properties of H171D and C172D indicate that these point mutations have
      not visible effects on the quaternary structure of SmNir. Both variants are
      catalytically incompetent using the physiological electron donor pseudoazurin,
      though C172D presents catalytic activity with the artificial electron donor
      methyl viologen (kcat=3.9(4) s-1) lower than that of wt SmNir (kcat=240(50) s-1).
      QM/MM calculations indicate that the lack of activity of H171D may be ascribed to
      the Ndelta1H...OC hydrogen bond that partially shortcuts the T1-T2 bridging Cys
      His covalent pathway. The role of the Ndelta1H...OC hydrogen bond in the pH
      dependent catalytic activity of wt SmNir is also analyzed by monitoring the T1
      and T2 oxidation states at the end of the catalytic reaction of wt SmNir at pH6
      and 10 by UV-vis and EPR spectroscopies. These data provide insight into how
      changes in Cys-His bridge interrupts the electron transfer between T1 and T2 and
      how the pH-dependent catalytic activity of the enzyme are related to pH-dependent
      structural modifications of the T1-T2 bridging chemical pathway.

PMID- 29051067
TI  - Identification, characterization, immobilization, and mutational analysis of a
      novel acetylesterase with industrial potential (LaAcE) from Lactobacillus
      acidophilus.
AB  - Lactic acid bacteria, which are involved in the fermentation of vegetables,
      meats, and dairy products, are widely used for the productions of small organic
      molecules and bioactive peptides. Here, a novel acetylesterase (LaAcE) from
      Lactobacillus acidophilus NCFM was identified, functionally characterized,
      immobilized, and subjected to site-directed mutagenesis for biotechnological
      applications. The enzymatic properties of LaAcE were investigated using
      biochemical and biophysical methods including native polyacrylamide gel
      electrophoresis, acetic acid release, biochemical assays, enzyme kinetics, and
      spectroscopic methods. Interestingly, LaAcE exhibited the ability to act on a
      broad range of substrates including glucose pentaacetate, glyceryl tributyrate,
      fish oil, and fermentation-related compounds. Furthermore, immobilization of
      LaAcE showed good recycling ability and high thermal stability compared with free
      LaAcE. A structural model of LaAcE was used to guide mutational analysis of
      hydrophobic substrate-binding region, which was composed of Leu156, Phe164, and
      Val204. Five mutants (L156A, F164A, V204A, L156A/F164A, and L156A/V204A) were
      generated and investigated to elucidate the roles of these hydrophobic residues
      in substrate specificity. This work provided valuable insights into the
      properties of LaAcE, and demonstrated that LaAcE could be used as a model enzyme
      of acetylesterase in lactic acid bacteria, making LaAcE a great candidate for
      industrial applications.

PMID- 29051068
TI  - Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to
      peroxynitrite-modified human DNA.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease
      characterized by auto-antibodies against native deoxyribonucleic acid after
      modification and is one of the reasons for the development of SLE. Here, we have
      evaluated the structural perturbations in human placental DNA by peroxynitrite
      using spectroscopy, thermal denaturation and high-performance liquid
      chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional
      oxidative/nitrative agent that is produced both endogenously and exogenously. In
      experimental animals, the peroxynitrite-modified DNA was found to be highly
      immunogenic. The induced antibodies showed cross-reactions with different types
      of DNA and nitrogen bases that were modified with peroxynitrite by inhibition
      ELISA. The antibody activity was inhibited by approximately 89% with its
      immunogen as the inhibitor. The antigen-antibodies interaction between induced
      antibodies with peroxynitrite-modified DNA showed retarded mobility as compared
      to the native form. Furthermore, significantly increased binding was also
      observed in SLE autoantibodies with peroxynitrite-modified DNA than native form.
      Moreover, DNA isolated from lymphocyte of SLE patients revealed significant
      recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data
      indicates that DNA modified with peroxynitrite presents unique antigenic
      determinants that may induce autoantibody response in SLE.

PMID- 29051069
TI  - Procyanidins from Cinnamomi Cortex promote proteasome-independent degradation of
      nuclear Nrf2 through phosphorylation of insulin-like growth factor-1 receptor in
      A549 cells.
AB  - Many lines of evidence demonstrate that transcription factor nuclear factor-E2
      related factor 2 (Nrf2) plays essential roles in cancer cell proliferation and
      resistance to chemotherapy, thereby indicating that suppression of abnormal Nrf2
      activation is needed for a new therapeutic approach. Our previous studies
      reported that procyanidins prepared from Cinnamomi Cortex extract (CCE) have an
      ability to suppress cytoprotective enzymes and cell proliferation in human cancer
      cells with activated Nrf2. In the present study, we investigated the mechanism of
      CCE procyanidin-mediated antagonization of Nrf2. CCE procyanidin treatment
      rapidly reduced nuclear Nrf2 expression and phosphorylated insulin-like growth
      factor-1 receptor (IGF-1R) in A549 cells. Nrf2 protein expression in A549 cells
      with reduced IGF-1R expression and function was not affected by treatment with
      CCE procyanidins, which suggested that CCE procyanidins decreased Nrf2 through
      IGF-1R. Nrf2 suppression by CCE procyanidins was mitigated in the presence of
      protease inhibitors, not proteasome inhibitors. In addition, CCE procyanidin
      treatment led to enhancement of nuclear cysteine protease activity in A549 cells.
      Our findings suggest a novel mechanism by which CCE procyanidins can promote
      proteasome-independent degradation of nuclear Nrf2 through IGF-1R phosphorylation
      and cysteine protease activation.

PMID- 29051071
TI  - Increase of Bacillus badius Phenylalanine dehydrogenase specificity towards
      phenylalanine substrate by site-directed mutagenesis.
AB  - Phenylalanine dehydrogenase (PheDH) is a key enzyme in medical diagnostic for
      determining the amount of phenylalanine to detect phenylketonuria (PKU) disease.
      However, determination of phenylalanine can be usually disturbed in presence of
      tyrosine in blood samples. Position N145 of B.sphaericus PheDH, has been
      previously showed a crucial role in substrate binding, which corresponded by
      position V144 in B. badius PheDH. In this study, the PheDH of B. badius due to
      reasonable activity was cloned and subjected to site-directed mutagenesis at
      mentioned position, followed by kinetic and structural studies to find more
      exclusive mutants. The results showed that the V144L mutant considerably
      increases specificity toward phenylalanine and decreases toward l-tyrosine, while
      in V144N mutant, the specificity reduces toward phenylalanine and increases
      toward tyrosine. Moreover, concerning the mutated V144D, significantly reduced
      kcat and also decreased km value for phenylalanine relative to that of wild type.
      The Phe/Tyr specificity constant in V144L increased more than 4-fold compared to
      wild type, makes it to be a suitable candidate for more specific identification
      of PKU. Finally, docking and molecular dynamic simulation on wild type and
      mutants clarified the structural basis behind more specificity of V144L mutant
      for phenylalanine substrate.

PMID- 29051072
TI  - The next generation of leaders advocating for brain health.

PMID- 29051070
TI  - Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic phytol metabolism.
AB  - While prior studies focusing on male mice suggest a role for sterol carrier
      protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol
      metabolism, its role in females is unresolved. This issue was addressed using
      female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without
      or with 0.5% phytol. GC/MS showed that hepatic: i) phytol was absent and its
      branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control
      fed mice; ii) accumulation of phytol as well as its peroxisomal metabolite BCFAs
      (phytanic acid " pristanic and 2,3-pristenic acids) was increased by dietary
      phytol in WT females, but only slightly in WT males; iii) accumulation of phytol
      and BCFA was further increased by DKO in phytol-fed females, but much more
      markedly in males. Livers of phytol-fed WT female mice as well as phytol-fed DKO
      female and male mice also accumulated increased proportion of saturated straight
      chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver phytol
      accumulation was not due to increased SCP-2 binding/transport of phytol since SCP
      2 bound phytanic acid, but not its precursor phytol. Thus, the loss of Scp-2/Scp
      x contributed to a sex-dependent hepatic accumulation of dietary phytol and BCFA.

PMID- 29051073
TI  - Corrections.

PMID- 29051074
TI  - Pairing ultrasonography with endocrinology to elucidate underlying mechanisms of
      successful pregnancy in the northern fur seal (Callorhinus ursinus).
AB  - Reproductive success is one of the central tenets of conservation management
      programs, yet the inability to study underlying physiological processes in a
      minimally-invasive manner and the unpredictable nature of wild animal populations
      leaves large gaps in our knowledge of factors critical to successful reproduction
      in wild species. This study integrated ultrasonography of the reproductive tract
      and analysis of reproductive hormones in 172 northern fur seals (Callorhinus
      ursinus) to identify intrinsic factors associated with reinitiating embryonic
      growth at the end of diapause. Within the first 3-4 weeks of active gestation,
      pregnant fur seals (n = 126) had a larger corpus luteum and fewer antral
      follicles than non-pregnant fur seals, or those still in diapause (n = 46). This
      suggests that the conceptus drives changes in ovarian status to convey its
      presence to the female. Morphological changes in the reproductive tract
      associated with pregnancy were not reflected in differences in endocrine profiles
      (estradiol, estrone, progesterone, and relaxin) between pregnant and non-pregnant
      individuals. Hormone concentrations correlated more strongly with calendar date
      than with the presence or size of the conceptus, demonstrating that none of these
      reproductive hormones were reliable markers for early pregnancy diagnosis.
      Instead, the northern fur seal's long diestrus may serve to reduce the
      probability of a temporal mismatch between corpus luteum regression and embryo
      implantation. Indeed, conception rates were high and confirmed rates of pregnancy
      loss were relatively low (11%). In this study, minimally-invasive ultrasonography
      was used in wild pinnipeds to detect very early pregnancy (embryonic vesicles >2
      mm) in combination with ovarian and endocrine dynamics at the time of embryo
      implantation, shedding light on mechanisms for maternal recognition of pregnancy.
      This study is also the first to track whether these same animals carried the
      embryo to term, by observing fur seals during the birthing season the following
      year. Data do not support the notion that decreased pregnancy rates or higher
      pregnancy loss rates are major contributing factors to the northern fur seal's
      population decline.

PMID- 29051075
TI  - The evolution and functional characterization of lined seahorse (Hippocampus
      erectus) CCKs involved in fasting and thermal stress response.
AB  - The peptide cholecystokinin (CCK) plays an important role in the regulation of
      vertebrate appetite and feeding behaviour. In the present study, the full-length
      cDNA and genomic DNA sequences of two CCK precursors were cloned and analysed in
      the Syngnathidae fish, the lined seahorse (Hippocampus erectus). Both CCK1 and
      CCK2 in the seahorse consist of four exons. The sequence of the octapeptide of
      seahorse CCK1 (DYMGWMDF) was the same as that of the chicken and human, while the
      octapeptide of seahorse CCK2 (DYEGWMDF) was unique among vertebrates. According
      to the phylogenetic analysis, two types of CCKs were produced by teleost-specific
      genome duplication (TGD). Both CCK1 and CCK2 were highly expressed in the brain,
      while detectable amounts of CCK1 mRNA in the brood pouch and CCK2 mRNA in the
      intestine were also found. Both CCK1 and CCK2 mRNA levels significantly increased
      during the transition from endogenous to exogenous nutrition. Additionally,
      fasting induced a significant increase in the CCK1 mRNA expression in the brain
      of juvenile seahorses but had no effect on CCK2 transcript levels. In addition,
      the CCK1 and CCK2 mRNA levels in the seahorse brain significantly increased after
      a high-temperature treatment. Thus, the mRNA expression of CCK had obvious tissue
      specificities and this preliminary study opens new avenues for further functional
      studies on the endocrine regulations of CCK in the transition from endogenous to
      exogenous nutrition, food intake regulation and metabolism in the seahorse.

PMID- 29051076
TI  - Behavioral phenotype predicts physiological responses to chronic stress in
      proactive and reactive birds.
AB  - Animal species display significant variation in personality traits among
      individuals, and two main coping styles have been identified and termed
      "proactive" and "reactive". Further, these coping styles appear to correlate
      directly with the strength of the physiological stress response exhibited by
      those individuals. In our study system, white laying hens are reactive, flighty,
      and exhibit large hormonal and behavioral responses to acute stress, while brown
      laying hens are proactive, exploratory, and exhibit low hormonal and behavioral
      responses to acute stress. The objective of the current study was to determine if
      personality type also corresponds to differences in multiple measures of stress
      when birds are subjected to a chronic stressor. We tested the responses of hens
      to chronic stress applied by providing feed according to an unpredictable
      schedule for 14 days, and measured corticosterone concentrations in circulation,
      expression of heat shock proteins (HSPs), molecules known to protect cells in
      response to stress, and the ratios of heterophils:lymphocytes in blood, two
      immune cells known to change in quantity in circulation during chronic stress. We
      predicted that white hens would show greater physiological responses to the
      chronic stress treatment. Plasma corticosterone levels significantly increased
      after 7 days of treatment and returned to baseline levels on day 14, but did not
      differ significantly between strains. H:L ratios, on the other hand, were
      significantly elevated by day 7 of treatment, and increased significantly more in
      brown hens than white. HSP70 and HSP90 expression levels were significantly
      higher after stress began in white hens than brown. Our results showed that brown
      hens were more reactive in one response (H:L ratios) while white hens were more
      reactive in another (HSP expression). These different reactions to the same
      stressor may represent different strategies for dealing with the same stressor.

PMID- 29051077
TI  - Cellular Proliferation by Multiplex Immunohistochemistry Identifies High-Risk
      Multiple Myeloma in Newly Diagnosed, Treatment-Naive Patients.
AB  - INTRODUCTION: Therapeutic options for multiple myeloma (MM) are growing, yet
      clinical outcomes remain heterogeneous. Cytogenetic analysis and disease staging
      are mainstays of risk stratification, but data suggest a complex interplay
      between numerous abnormalities. Myeloma cell proliferation is a metric shown to
      predict outcomes, but available methods are not feasible in clinical practice.
      PATIENTS AND METHODS: Multiplex immunohistochemistry (mIHC), using multiple
      immunostains simultaneously, is universally available for clinical use. We tested
      mIHC as a method to calculate a plasma cell proliferation index (PCPI). By mIHC,
      marrow trephine core biopsy samples were costained for CD138, a plasma cell
      specific marker, and Ki-67. Myeloma cells (CD138+) were counted as proliferating
      if coexpressing Ki-67. Retrospective analysis was performed on 151 newly
      diagnosed, treatment-naive patients divided into 2 groups on the basis of myeloma
      cell proliferation: low (PCPI <= 5%, n = 87), and high (PCPI > 5%, n = 64).
      RESULTS: Median overall survival (OS) was not reached versus 78.9 months (P =
      .0434) for the low versus high PCPI groups. Multivariate analysis showed that
      only high-risk cytogenetics (hazard ratio [HR] = 2.02; P = .023), International
      Staging System (ISS) stage > I (HR = 2.30; P = .014), and PCPI > 5% (HR = 1.70; P
      = .041) had independent effects on OS. Twenty-three (36%) of the 64 patients with
      low-risk disease (ISS stage 1, without high-risk cytogenetics) were uniquely
      reidentified as high risk by PCPI. CONCLUSION: PCPI is a practical method that
      predicts OS in newly diagnosed myeloma and facilitates broader use of MM cell
      proliferation for risk stratification.

PMID- 29051078
TI  - The Role of Radiation in All Stages of Nodular Lymphocytic Predominant Hodgkin
      Lymphoma.
AB  - BACKGROUND: The goal of this study was to assess the survival differences seen in
      early-stage and advanced-stage nodular lymphocytic predominant Hodgkin lymphoma
      (NLPHL) based on treatment modality. PATIENTS AND METHODS: The National Cancer
      Database was queried to identify patients diagnosed with NLPHL between 2004 and
      2012. Overall survival (OS) was determined using univariate and multivariate Cox
      regression analysis. Kaplan-Meier and log-rank analysis were used to estimate
      differences in OS between treatment groups. RESULTS: A total of 1968 patients
      were identified for analysis, consisting of stage I (40.4%), stage II (29.3%),
      stage III (22.3%), and stage IV (8.0%) disease. The median age of patients was 46
      years. The following factors were predictive of radiotherapy (RT) omission in
      treatment: increasing age, black race, Medicare insurance, chemotherapy use,
      stage II to IV disease, and the presence of B-symptoms. On survival analysis, RT
      was associated with prolonged OS in all stages of NLPHL (50.1 vs. 42.4 months; P
      < .01). The OS benefit of RT persisted on multivariate analysis (hazard ratio,
      0.37; P < .01). On subset analysis, RT was associated with prolonged OS in early
      disease (49.8 vs. 45.5 months; P < .01), whereas a trend towards an OS benefit
      was observed in advanced-stage (54.1 vs. 39.6 months; P = .06) NLPHL.
      Radiotherapy was also associated with prolonged OS among patients with B-symptoms
      (49.0 vs. 42.6 months; P < .01). CONCLUSION: The use of RT in NLPHL is less
      likely among those with advanced-stage disease and B-symptoms. However, we found
      RT to be associated with prolonged OS in all stages of NLPHL, including those
      with B-symptoms.

PMID- 29051079
TI  - Reduced Myocardial Flow Reserve Is Associated With Diastolic Dysfunction and
      Decreased Left Atrial Strain in Patients With Normal Ejection Fraction and
      Epicardial Perfusion.
AB  - INTRODUCTION: Coronary microvascular dysfunction (MVD) may contribute to the
      pathogenesis of heart failure with preserved ejection fraction (HFpEF). Using
      myocardial flow reserve (MFR) measured by positron emission tomography (PET) as
      an assessment of microvascular function, we hypothesized that abnormal MFR is
      associated with LV diastolic dysfunction (DD) and reduced LV and LA strain in
      patients with risk factors for HFpEF and normal epicardial perfusion on cardiac
      PET. METHODS AND RESULTS: Retrospective study of patients without heart failure
      who underwent cardiac rubidium-82 PET and echocardiography. Global MFR was
      calculated as the ratio of global stress to rest myocardial blood flow.
      Echocardiographic measures of diastolic function were recorded. Global
      longitudinal LA and LV strain were measured with a 2-dimensional speckle-tracking
      technique. Relationships among MFR and echocardiographic measures were assessed
      with linear regression, analysis of variance, and test for trend. Seventy-three
      patients (age 64 +/- 11 years, 52% male) were identified with no epicardial
      perfusion defect on cardiac PET and an ejection fraction >=50%. Decreased MFR was
      associated with LV DD (P = .02) and increased E/e', an estimation of LV filling
      pressure (low E/e' [<8] vs. high E/e' [>15], P < .001). MFR was associated with
      LA strain independent of age, gender, and common comorbidities (adjusted beta =
      2.6% per unit MFR, P = 0.046); however, MFR was only marginally related to LV
      strain. CONCLUSIONS: In patients with risk factors for HFpEF, MVD assessed with
      MFR was associated with DD, increased estimated LV filling pressure, and abnormal
      LA strain.

PMID- 29051080
TI  - Antiviral activity of N-(4-hydroxyphenyl) retinamide (4-HPR) against Zika virus.
AB  - The rapid spread of Zika virus (ZIKV) in recent years has highlighted the severe
      diseases associated with ZIKV infection, such as Guillain-Barre syndrome in
      adults and microcephaly in newborns; yet no vaccines or antivirals currently
      exist to prevent or treat ZIKV infection. We and others have previously
      identified N-(4-hydroxyphenyl) retinamide (fenretinide or 4-HPR) as an antiviral
      compound that inhibits dengue virus 2 (DV2) and other flaviviruses by limiting
      the steady-state accumulation of viral RNA. Here we show that 4-HPR potently
      inhibits ZIKV in mammalian cell culture and significantly reduces both serum
      viremia and brain viral burden in a murine model of ZIKV infection. Consistent
      with previous observations with dengue virus, this antiviral activity is
      associated with a significant reduction in the steady-state abundance of viral
      genomic RNA. We show this reduction is due to a major decrease in the rate of
      viral RNA synthesis, though not via direct inhibition of the activity of the
      viral replicase. These results establish 4-HPR's mode of action against DV and
      ZIKV and, taken with previous clinical trials that established 4-HPR's safety and
      tolerability, illustrate the potential utility of 4-HPR as an agent for treatment
      of ZIKV infection.

PMID- 29051081
TI  - Comparative proteomic analyses using iTRAQ-labeling provides insights into fiber
      diversity in sheep and goats.
AB  - : The structural component of wool and hair fibers, such as keratin-associated
      proteins (KAPs), has been well described, but the genetic determinants of fiber
      diameter are largely unknown. Here, we have used an iTRAQ-based proteomic
      approach to investigate differences in protein abundance among 18 samples from
      sheep and goats across a diverse range of fibers. We identified proteins with
      different abundance and are associated with variation in fiber features. Proteins
      with different abundance are mainly keratin or keratin-associated proteins
      (KRTAP11-1, KRT6A, KRT38), or are related to hair growth (DSC2, DSG3, EEF2,
      CALML5, TCHH, SELENBP1) and fatty acid synthesis (FABP4, FABP5). RNA-seq further
      confirmed the functional importance of the DSC2 gene in the determination of
      woolly phenotype in goat fibers. This comprehensive analysis of fibers from major
      fiber-producing animals is the first to provide a list of candidate proteins that
      are involved in fiber formation. This list will be valuable asset for future
      studies into the molecular mechanisms that underlie fiber diversity. BIOLOGICAL
      SIGNIFICANCE: Proteins are the basis for animal-derived hair fibers, yet proteins
      conferring fiber structure and characteristics in sheep and goats are largely
      elusive. By examining 27 fibers samples representing 9 fiber types from sheep and
      goats through the iTRAQ approach, we show a list of differentially abundant
      proteins that are important to hair structural component, or genes related to
      hair growth and fatty acid synthesis. RNA-seq further validated the DSC2 gene is
      key to the woolly/straight hair phenotype in goats.

PMID- 29051082
TI  - Magnetic capture of polydopamine-encapsulated Hela cells for the analysis of cell
      surface proteins.
AB  - : A novel method to characterize cell surface proteins and complexes has been
      developed. Polydopamine (PDA)-encapsulated Hela cells were prepared for plasma
      membrane proteome research. Since the PDA protection, the encapsulated cells
      could be maintained for more than two weeks. Amino groups functionalized magnetic
      nanoparticles were also used for cell capture by the reaction with the PDA
      coatings. Plasma membrane fragments were isolated and enriched with assistance of
      an external magnetic field after disruption of the coated cells by ultrasonic
      treatment. Plasma membrane proteins (PMPs) and complexes were well preserved on
      the fragments and identified by shot-gun proteomic analytical strategy. 385 PMPs
      and 1411 non-PMPs were identified using the method. 85.2% of these PMPs were
      lipid-raft associated proteins. Ingenuity Pathway Analysis was employed for bio
      information extraction from the identified proteins. It was found that 653 non
      PMPs had interactions with 140 PMPs. Among them, epidermal growth factor receptor
      and its complexes, and a series of important pathways including STAT3 pathway
      were observed. All these results demonstrated that the new approach is of great
      importance in applying to the research of physiological function and mechanism of
      the plasma membrane proteins. SIGNIFICANCE: This work developed a novel strategy
      for the proteomic analysis of cell surface proteins. According to the results,
      73.3% of total identified proteins were lipid-raft associated proteins, which
      imply that the proposed method is of great potential in the identification of
      lipid-raft associated proteins. In addition, a series of protein-protein
      interactions and pathways related to Hela cells were pointed out. All these
      results demonstrated that our proposed approach is of great importance and could
      well be applied to the physiological function and mechanism research of plasma
      membrane proteins.

PMID- 29051083
TI  - Lysophosphatidic acid propagates post-injury Schwann cell dedifferentiation
      through LPA1 signaling.
AB  - Lysophosphatidic acid (LPA) is a pleiotropic signaling lipid that acts as ligand
      for at least six specific G-protein coupled receptors. Schwann cells (SC) are
      known to mainly express the LPA1 receptor subtype. An emerging body of evidence
      has linked LPA with injury-induced peripheral nerve demyelination as well as
      neuropathic pain. However, the molecular mechanisms underlying its demyelinating
      effect have not been conclusively elucidated. We aimed to decipher the
      demyelinating effect in vitro as well as in vivo by studying markers of SC
      differentiation and dedifferentiation: Myelinated dorsal root ganglia (DRG)
      cultures were treated either with LPA, LPA plus AM095 (LPA1 antagonist) or
      vehicle. Myelin content was subsequently investigated by Sudan Black staining and
      immunocytochemistry. In vivo, we performed sciatic nerve crush in C57BL/6 mice
      treated with AM095 at 10mg/kg. In DRG cultures, LPA caused a significant
      reduction of myelin as demonstrated by both Sudan Black staining and
      immunocytochemical analysis of myelin basic protein. Demyelination was paralleled
      by an upregulation of TNF-alpha as well as downregulation of Sox10, a marker for
      SC differentiation. LPA mediated effects were largely blocked by the addition of
      the LPA1 receptor antagonist AM095. In the in vivo model, AM095 treatment prior
      to crush injury increased Sox10 expression in SCs in the distal nerve stump while
      reducing the number of cells expressing the SC dedifferentiation marker Sox2.
      Additionally, TNF-alpha immunofluorescence was reduced in CD11b-positive cells.
      These data indicate that LPA may be a critical factor that shifts SCs towards a
      post-injury phenotype and contributes to the onset of Wallerian degeneration.

PMID- 29051084
TI  - High-fat diet reduces the hippocampal content level of lactate which is
      correlated with the expression of glial glutamate transporters.
AB  - Metabolic disorders hamper the brain metabolism and functions. The astrocytic
      glucose-derived lactate is known to fill the increased energy needs of neurons
      during synaptic transmission. However, whether systemic metabolism dysregulation
      affects the astrocytic lactate metabolism in the brain remain unexamined. To
      address this question, we adopt a 12-week high-fat diet to induce metabolic
      disorders in adult mice, and the effects of high-fat diet on the lactate
      metabolism in the hippocampus were examined. Results showed that a 12-week high
      fat diet induced obesity and insulin resistance in mice. High-fat diet also
      decreased the lactate content levels and the expression of glial glutamate
      transporters, GLAST and GLT-1, in the hippocampus. Strong correlations between
      the lactate levels and the levels of GLAST and GLT-1 were evidenced. In
      conclusion, high-fat feeding induces metabolic disorders and disrupts lactate
      metabolism in the hippocampus. GLAST and GLT-1 may contribute to the HFD-induced
      abnormalities of the hippocampal lactate metabolism.

PMID- 29051085
TI  - 40Hz auditory steady-state response in schizophrenia: Sensitivity to stimulation
      type (clicks versus flutter amplitude-modulated tones).
AB  - Auditory steady-state response (ASSR) at 40Hz has been proposed as a potential
      biomarker for schizophrenia. The ASSR studies in patients have used click
      stimulation or amplitude-modulated tones. However, the sensitivity of 40Hz ASSRs
      to different stimulation types in the same group of patients has not been
      previously evaluated. Two stimulation types for ASSRs were tested in this study:
      (1) 40Hz clicks and (2) flutter-amplitude modulated tones. The mean phase-locking
      index, evoked amplitude and event-related spectral perturbation values were
      compared between schizophrenia patients (n=26) and healthy controls (n=20). Both
      stimulation types resulted in the observation of impaired phase-locking and power
      measures of late (200-500ms) 40Hz ASSR in patients compared to healthy controls.
      The early-latency (0-100ms) 40Hz ASSR part was diminished in the schizophrenia
      group in response to clicks only. The late-latency 40Hz ASSR parameters obtained
      through different stimulation types correlated in healthy subjects but not in
      patients. We conclude that flutter amplitude-modulated tone stimulation, due to
      its potential to reveal late-latency entrainment deficits, is suitable for use in
      clinical populations. Careful consideration of experimental stimulation settings
      can contribute to the interpretation of ASSR deficits and utilization as a
      potential biomarker.

PMID- 29051086
TI  - Depression subtyping based on evolutionary psychiatry: Proximate mechanisms and
      ultimate functions.
AB  - Major depressive disorder constitutes one of the leading causes of disability
      worldwide. However, it is not a unitary disease-it is a heterogeneous syndrome,
      with patients differing remarkably in symptom profile, pathophysiology and
      treatment responsiveness. Previous attempts to subtype major depressive disorder
      have showed limited clinical applicability. We present a classification of major
      depressive disorder episodes based on the proximate mechanisms that led to the
      original mood change that caused the depressive episode. We identify discrete
      depression subtypes that are induced by: 1) infection, 2) long-term stress, 3)
      loneliness, 4) traumatic experience, 5) hierarchy conflict, 6) grief, 7) romantic
      rejection, 8) postpartum events, 9) the season, 10) chemicals, 11) somatic
      diseases and 12) starvation. We further examine the ultimate functions of these
      subtypes and show that not all types of mood changes that trigger depression are
      adaptive. Instead, some are clearly maladaptive and some are byproducts of other
      adaptations. In modern societies, low mood after adverse life events may turn
      into a pathological depressive state. Modern lifestyle increases susceptibility
      to inflammatory dysregulation and chronic stress, both of which increase the
      amount of proinflammatory cytokines in peripheral blood, leading to low mood and
      sickness behaviour. Proinflammatory cytokines may aggravate the previously
      adaptive short-term mood changes to a chronic maladaptive depressive state by
      preventing the normalization of mood after adverse life events. Subtyping
      depression enables an effective and intelligent long-term treatment of patients
      in each subtype by treating the underlying causes of depression.

PMID- 29051087
TI  - Triggering receptor expressed on myeloid cells 2 (TREM2) dependent microglial
      activation promotes cisplatin-induced peripheral neuropathy in mice.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect
      of many antineoplastic agents. Patients treated with chemotherapy often report
      pain and paresthesias in a "glove-and-stocking" distribution. Diverse mechanisms
      contribute to the development and maintenance of CIPN. However, the role of
      spinal microglia in CIPN is not completely understood. In this study, cisplatin
      treated mice displayed persistent mechanical allodynia, sensory deficits and
      decreased density of intraepidermal nerve fibers (IENFs). In the spinal cord,
      activation of microglia, but not astrocyte, was persistently observed until week
      five after the first cisplatin injection. Additionally, mRNA levels of
      inflammation related molecules including IL-1beta, IL-6, tumor necrosis factor
      (TNF)-alpha, inducible nitric oxide synthase (iNOS) and CD16, were increased
      after cisplatin treatment. Intraperitoneal (i.p.) or intrathecal (i.t.) injection
      with minocycline both alleviated cisplatin-induced mechanical allodynia and
      sensory deficits, and prevented IENFs loss. Furthermore, cisplatin enhanced
      triggering receptor expressed on myeloid cells 2 (TREM2) /DNAX-activating protein
      of 12 kDa (DAP12) signaling in the spinal cord microglia. The blockage of TREM2
      by i.t. injecting anti-TREM2 neutralizing antibody significantly attenuated
      cisplatin-induced mechanical allodynia, sensory deficits and IENFs loss.
      Meanwhile, anti-TREM2 neutralizing antibody prominently suppressed the spinal IL
      6, TNF-alpha, iNOS and CD16 mRNA level, but it dramatically up-regulated the anti
      inflammatory cytokines IL-4 and IL-10. The data demonstrated that cisplatin
      triggered persistent activation of spinal cord microglia through strengthening
      TREM2/DAP12 signaling, which further resulted in CIPN. Functional blockage of
      TREM2 or inhibition of microglia both benefited for cisplatin-induced peripheral
      neuropathy. Microglial TREM2/DAP12 may serve as a potential target for CIPN
      intervention.

PMID- 29051088
TI  - Update on the role of Pentraxin 3 in atherosclerosis and cardiovascular diseases.
AB  - Pentraxin 3 (PTX3) is an acute-phase protein that was recently demonstrated to
      play pleiotropic activities in cardiovascular (CV) diseases. Tumor necrosis
      factor and interleukins up-regulates PTX3 transcription in different cell types
      (i.e. endothelial cells, phagocytes, smooth muscle cells, fibroblasts and glial
      cells) involved in atherogenesis. By interacting with numerous ligands, PTX3 acts
      as a modulatory molecule of complement system, inflammatory response,
      angiogenesis, and vascular/tissue remodeling. Experimental data point to a
      beneficial role of PTX3 in atherosclerotic plaque development and vulnerability.
      Animal studies indicated a protective role of PTX3 signaling in
      ischemic/reperfusion injury and failing heart. Clinical studies have so far
      provided contrasting results, highlighting a debated role of PTX3 as an active
      mediator of endothelial dysfunction, atherosclerotic plaque vulnerability and
      worse outcome after ischemic events. Therefore, substantial evidence suggests a
      dual role of PTX3 as modulator or amplifiers of the innate immune response. The
      final result of PTX3 activation might be determined by a fine tuning of time,
      space and environmental signals. The aim of this review is to provide an overview
      of biological properties of PTX3 in CV diseases and to discuss the ability of
      PTX3 to act as a crossroad between pro- and anti-inflammatory pathways.

PMID- 29051089
TI  - Glycosylation of hemocyanin in Litopenaeus vannamei is an antibacterial response
      feature.
AB  - Hemocyanin is an important multifunctional non-specific immune molecule. In this
      study, we purified lectin binding and non-lectin binding hemocyanin from
      Litopenaeus vannamei using Concanavalin A (ConA) lectin affinity chromatography
      (designated HMC-C and HMC-NC, respectively). Analysis of the carbohydrate content
      showed that HMC-C had about 20 times as much carbohydrate as HMC-NC. 54 and 42
      peaks were observed in HMC-C and HMC-NC by HPLC, which reduced to 49 and 6 peaks,
      respectively, when digested with trypsin and repurified with ConA lectin column.
      Further, the agglutinative activity of HMC-C against two pathogenic bacteria,
      Vibrio alginolyticus and Vibrio fluvialis, was about 8-fold and 4-fold,
      respectively, to that of HMC-NC. While the antibacterial activity of HMC-NC was
      about 30% lower compared with HMC-C. Similarly, when HMC was deglycosylated using
      O-glycosidase, its agglutinative activity reduced about 4-8 fold. Most
      importantly, when shrimps were challenged with V. alginolyticus or V. fluvialis,
      the glycan content of hemocyanin increased dramatically and remained high at the
      earlier time points (24-72h) post infection, only decreasing after 96 hpi. Taken
      together, these results suggest that hemocyanin glycosylation plays an important
      role in its antibacterial properties.

PMID- 29051090
TI  - Comparative one- and two-photon uncaging of MNI-glutamate and MNI-kainate on
      hippocampal CA1 neurons.
AB  - BACKGROUND: The light-induced release of neurotransmitters from caging
      chromophores provides a powerful means to study the underlying receptors in a
      physiologically relevant context. Surprisingly, most caged neurotransmitters,
      including the widely used 4-methoxy-7-nitroindolinyl (MNI)-glutamate, show strong
      antagonism against GABA-A receptors. Kainate has been shown to exhibit a higher
      efficacy at glutamate receptors compared to glutamate itself. Thus, uncaging of
      kainate might allow the application of the caged compound at lower, less
      antagonistic concentrations. NEW METHODS: This study provides a detailed
      comparison of MNI-glutamate and MNI-kainate uncaging by different modes of one-
      and two-photon irradiation on hippocampal CA1 pyramidal neurons in acute brain
      slices. RESULTS/COMPARISON WITH EXISTING METHODS: Unexpectedly, the data revealed
      that currents in response to MNI-glutamate uncaging were larger compared to MNI
      kainate with local one-photon laser uncaging at the soma and two-photon uncaging
      at the same spines. Furthermore, the direct comparison demonstrates the influence
      of type of caged agonist and light delivery conditions used for uncaging on the
      amplitude and kinetic properties of the current response. CONCLUSION: These
      findings highlight the importance of experimental design for uncaging experiments
      and provide a basis for future studies employing one- and two-photon uncaging to
      understand glutamate-dependent processes. It further provides the first example
      of two-photon uncaging of kainate at single spines in acute brain slices.

PMID- 29051091
TI  - Theta-phase closed-loop stimulation induces motor paradoxical responses in the
      rat model of Parkinson disease.
AB  - BACKGROUND: High-frequency deep brain stimulation (DBS) has become a widespread
      therapy used in the treatment of Parkinson's Disease (PD) and other diseases.
      Although it has proved beneficial, much recent attention has been centered around
      the potential of new closed-loop DBS implementations. OBJECTIVE: Here we present
      a new closed-loop DBS scheme based on the phase of the theta activity recorded
      from the motor cortex. By testing the implementation on freely moving 6-OHDA
      lesioned and control rats, we assessed the behavioral and neurophysiologic
      effects of this implementation and compared it against the classical high
      frequency DBS. RESULTS: Results show that both stimulation modalities produce
      significant and opposite changes on the movement and neurophysiological activity.
      Close-loop stimulation, far from improving the animals' behavior, exert contrary
      effects to those of high-frequency DBS which reverts the parkinsonian symptoms.
      Motor improvement during open-loop, high-frequency DBS was accompanied by a
      reduction in the amount of cortical beta oscillations while akinetic and
      disturbed behavior during close-loop stimulation coincided with an increase in
      the amplitude of beta activity. CONCLUSION: Cortical-phase-dependent close-loop
      stimulation of the STN exerts significant behavioral and oscillatory changes in
      the rat model of PD. Open-loop and close-loop stimulation outcomes differed
      dramatically, thus suggesting that the scheme of stimulation determines the
      output of the modulation even if the target structure is maintained. The current
      framework could be extended in future studies to identify the correct parameters
      that would provide a suitable control signal to the system. It may well be that
      with other stimulation parameters, this sort of DBS could be beneficial.

PMID- 29051092
TI  - Targeted surveillance of nosocomial infection in intensive care units of 176
      hospitals in Jiangsu province, China.
AB  - BACKGROUND: Nosocomial infections (NIs) impact care and costs in hospitals across
      the globe. There are few data on targeted surveillance of NI in intensive care
      units (ICUs), and data specific to the risk factors for NI are especially
      limited. METHODS: One hundred and seventy-six secondary and tertiary hospitals
      performed NI targeted surveillance in their ICUs. The data were collected and
      summarized by Minke software, then fed back once per quarter. FINDINGS: The
      incidence of NI appeared to decrease, and the incidence of NI per 1000 patient
      days and adjusted incidence were 25.630/00 and 7.410/00 in 2010, and 9.730/00 and
      2.760/00 in 2015, respectively. The NI incidence in general hospitals was higher
      than in specialized hospitals. The incidence of central-line-associated
      bloodstream infection (CLABSI) and catheter-associated urinary tract infection
      (CAUTI) appeared to decrease, and the incidence of ventilator-associated
      pneumonia (VAP) decreased markedly from 20.330/00 to 2.760/00. There was no
      statistically significant difference among ICUs. The six most frequently found
      pathogen-caused NIs were Acinetobacter baumannii (AB), Klebsiella pneumoniae
      (KP), Pseudomonas aeruginosa (PA), Staphylococcus aureus, Candida albicans, and
      Escherichia coli (E. coli). The isolation rate of carbapenem-resistant Gram
      negative bacilli were carbapenem-resistant AB 80.53%, carbapenem-resistant PA
      39.94%, carbapenem-resistant KP (CRKP) 24.86%, and carbapenem-resistant E. coli
      9.23%. The isolation rate of meticillin-resistant S. aureus (MRSA) was 66.30%.
      The increasing trend of CRKP was statistically significant as analysed by the
      regression model. CONCLUSION: The incidences of VAP, CAUTI, and CLABSI were high
      in ICUs, and multidrug-resistant organisms were the primary pathogens of NI. The
      implementation of targeted surveillance may determine the risk factors of NI so
      that effective intervention measures can be taken to reduce the incidence of NI
      in ICU patients.

PMID- 29051093
TI  - Purification and analysis of the composition and antioxidant activity of
      polysaccharides from Helicteres angustifolia L.
AB  - The antioxidant activity of polysaccharides has attracted tremendous research
      interest in recent years. In this study, we aimed to investigate the antioxidant
      properties of Helicteres angustifolia L. polysaccharides (HALP) that was acquired
      by water extraction and alcohol precipitation using ultrasound-assisted method
      with decolorization and protein removal. The polysaccharides were then
      successively purified using chromatography on DEAE-cellulose and Sephadex S-300
      columns with two major fractions: HALPs1-1 and HALPs2-1. The physicochemical
      properties, structural characterization, and antioxidant activities of these
      fractions were investigated. The results indicated that HALPs1-1 was a glucan
      with an average molecular weight of 151.70kDa, and HALPs2-1 was composed of
      glucuronic acid with an average molecular weight of 114.81kDa. Infrared
      spectroscopies and iodine potassium iodide tests showed that the HALP were acid
      alpha-pyranoses. The antioxidant activities of the polysaccharide fractions
      (HALP, HALPs1-1, and HALPs2-1) were evaluated in vitro. The results suggested
      that HALPs2-1 had the highest scavenging activities for ABTS, hydroxyl and DPPH
      radicals than other polysaccharides. Taken together, the results of this study
      suggested that polysaccharides from Helicteres angustifolia L. could be used as
      novel potential antioxidants.

PMID- 29051094
TI  - Modification of proteins and polysaccharides using dodecenyl succinic anhydride:
      Synthesis, properties and applications-A review.
AB  - Proteins and polysaccharides are among the biopolymers produced by living
      organisms for their structural integrity, protection, physiological functions, or
      as reserve energy. These biopolymers are extracted from their natural matrices by
      humans to fulfil basic as well as convenience needs. The inquisitive human
      nature, ever-growing demands and resources at disposal have led to copious
      research in the field of biopolymer modifications. The availability of reactive
      sites on these biopolymers make them suitable substrates for esterification,
      etherification, oxidation, epoxidation, N-acylation, alkylation, etc. Dodecenyl
      succinic anhydride (DDSA) is an esterifying agent that introduces a 12-carbon
      hydrophobic chain in the structure of the substrate containing suitable reactive
      sites. The use of DDSA as a modifying agent for biopolymers dates back to the mid
      twentieth century. Even today, many biopolymers are explored for modification
      with DDSA for improved functionality. These modifications are aimed at catering
      the needs of the paint, pharmaceutical, cosmetic, food and textile industries.
      This review attempts to systematically compile reported research on the use of
      DDSA as a biopolymer modifying agent, the various reaction techniques, properties
      and applications thereof.

PMID- 29051095
TI  - Characterization of a dextran produced by Leuconostoc pseudomesenteroides XG5
      from homemade wine.
AB  - A water-souble exopolysaccharide (EPS) produced by Leuconostoc
      pseudomesenteroides XG5 from homemade wine was investigated. The EPS yield of
      35.5g/L was achieved at 30 degrees C for 48h in De Man-Rogosa-Sharpe (MRS) medium
      containing 12.5% sucrose. The EPS was a dextran composed exclusively of glucose
      and the molecular weight was 2.6*106Da. Fourier transform infrared spectra and
      nuclear magnetic resonance spectra revealed that the EPS was a dextran containing
      D-glucose residues in a linear chain with consecutive alpha-(1->6) linkages.
      Scanning electron microscopy of the EPS appeared a highly branched and porous
      structure. Rheological studies showed that the EPS had higher viscosity in 0.1M
      KCl solution, at lower temperature, or at acidic pH. Thermal gravimetric analysis
      and differential scanning calorimetric indicated that the EPS had excellent
      thermal stability with a degradation temperature of 313.80 degrees C and melting
      point at 274.14 degrees C. Water solubility index and water holding capacity of
      XG5 dextran were 90.2% and 412% respectively. The results suggest that L.
      pseudomesenteroides XG5 might be widely used in the production of linear dextran
      which has potential to serve as natural agent applied in food and other fields.

PMID- 29051096
TI  - Ultrasound assisted extraction of polysaccharides from Lentinus edodes and its
      anti-hepatitis B activity in vitro.
AB  - The aim of this study was to optimize the extraction process of polysaccharides
      from the fruiting bodies of Lentinus edodes and investigate its anti-hepatitis B
      virus activity. The extracting parameters including ultrasonic power (240-320W),
      extraction temperature (40-60 degrees C) and extraction time (15-25min) was
      optimized by using three-variable-three-level Box-Behnken design based on the
      single-factor experiments. Data analysis results showed that the optimal
      conditions for extracting LEPs were an extraction temperature of 45 degrees C,
      extraction time of 21min and ultrasonic power of 290W. Under these optimal
      conditions, the experimental yield of LEPs was 9.75%, a 1.62-fold increase
      compared with conventional heat water extraction (HWE). In addition, crude
      polysaccharides were purified to obtain two fractions (LEP-1 and LEP-2). Chemical
      analysis showed that these components were rich in glucose, arabinose and
      mannose. Furthermore, HepG2.2.15 cells were used as in vitro models to evaluate
      their anti-hepatitis B virus (HBV) activity. The results suggest that LEPs
      possesses potent anti-HBV activity in vitro.

PMID- 29051097
TI  - Production of low-molecular weight soluble yeast beta-glucan by an acid
      degradation method.
AB  - beta-glucan is widely distributed in nature as water soluble and insoluble forms.
      Both forms of beta-glucan are utilized in several fields, especially for
      functional foods. Yeast beta-glucan is a medically important insoluble particle.
      Solubilization of yeast beta-glucan may be valuable for improving functional
      foods and in medicinal industries. In the present study, we applied an acid
      degradation method to solubilize yeast beta-glucan and found that beta-glucan was
      effectively solubilized to low-molecular weight beta-glucans by 45% sulfuric acid
      treatment at 20 degrees C. The acid-degraded soluble yeast beta-glucan (ad-sBBG)
      was further fractionated into a higher-molecular weight fraction (ad-sBBG-high)
      and a lower-molecular weight fraction (ad-sBBG-low). Since ad-sBBG-high contained
      mannan, while ad-sBBG-low contained it only scarcely, it was possible to prepare
      low-molecular weight soluble beta-glucan with higher purity. In addition, ad-sBBG
      low bound to dectin-1, which is an innate immunity receptor of beta-glucan, and
      showed antagonistic activity against reactive oxygen production and cytokine
      synthesis by macrophages. Thus, this acid degradation method is an important
      procedure for generating immune-modulating, low-molecular weight, soluble yeast
      beta-glucan.

PMID- 29051098
TI  - Impact of tyrosine nitration at positions Tyr307 and Tyr335 on structural
      dynamics of Lipoprotein-associated phospholipase A2-A therapeutically important
      cardiovascular biomarker for atherosclerosis.
AB  - Protein tyrosine nitration (PTN) is a post translational event which results in
      the generation of 3-Nitrotyrosine (3-NT). High levels of 3-NT were reported in
      several human diseases such as Parkinson's disease, Alzheimer's disease,
      amylotrophic lateral sclerosis and coronary artery disease. It was reported that
      PTN at positions 307 and 335 of Lipoprotein-associated phospholipase A2 (Lp-PLA2)
      curtails its enzymatic activity but the mechanism of inhibition at the structure
      level is still incomprehensible. The present study is an in silico endeavor to
      understand nitrative stress induced structural changes in Lp-PLA2. Molecular
      docking studies revealed a decreased binding affinity of substrate, Platelet
      Activating Factor (PAF) with the nitrated forms of Lp-PLA2 (NT-Tyr307 and NT
      Tyr335) compared to the wild type, due to differences in the hydrogen bond
      interaction patterns. Molecular dynamics (MD) simulation studies suggests higher
      flexibility of nitrated forms compared to wild type, disorientation of the
      catalytic triad and decreased molecular interactions of NT-Tyr307 and NT-Tyr335
      with other residues of the protein. Essential dynamics (ED) further confirmed the
      enhanced structural flexibility of nitrated forms of Lp-PLA2. Our findings would
      help understand the molecular mechanism of nitrative stress induced inhibition of
      Lp-PLA2 which may further assist in designing of therapeutics having protective
      functions against PTN.

PMID- 29051099
TI  - Hyperglycemia induced reactive species trigger structural changes in human serum
      albumin of type 1 diabetic subjects.
AB  - Chronic oxidative stress fuels pathogenesis of a large set of diseases. Oxidative
      stress is the cause and consequence of numerous diseases including type 1
      diabetes mellitus (T1DM), in which there is selective destruction of insulin
      producing pancreatic beta-cells. Studies have documented that hyperglycemia
      produces profound stress. In vivo production of numerous reactive oxygen,
      nitrogen, chlorine species and lipid/sugar oxidation products in T1DM patients
      may be the result of persistent hyperglycemia. Post-translational modifications
      by reactive species may create new antigenic epitopes and play a role in the
      development of autoimmune response. In this paper our main focus was to establish
      the effect of existing hyperglycemia induced oxido-nitrosative stress in T1DM
      patients on the integrity of human serum albumin. Raised nitric oxide, carbonyl,
      RBC hemolysis, lowered ferric reducing antioxidant power (FRAP), thiol and
      deformed RBC in T1DM are all highly suggestive of persistent oxido-nitrosative
      stress. Hyperglycemia induced generation of advanced glycation end products
      (AGEs) was established by LCMS. Chronic oxido-nitrosative stress can modify HSA
      in T1DM patients, producing immunologically active albumin. Therefore, it is
      speculated that the aberrant HSA may play a role in the initiation/progression of
      T1DM.

PMID- 29051100
TI  - Co-immobilization of glucose oxidase and catalase in silica inverse opals for
      glucose removal from commercial isomaltooligosaccharide.
AB  - In this work, glucose oxidase (GOD) and catalase (CAT) were co-immobilized on
      novel silica inverse opals (IO-SiO2) through sol-gel process. The immobilized bi
      enzyme system named GOD/CAT@IO-SiO2 was successfully fabricated and
      characterized. Morphology characterization indicated that GOD/CAT@IO-SiO2 had
      hierarchical porous structure, and the pore diameter of macroporous and
      mesoporous were 500+/-50nm and 6.8nm, respectively. The macrospores were
      connected through windows of 100+/-30nm. The results of stability tests indicated
      that both acid (or base) resistance and thermal tolerance of GOD/CAT@IO-SiO2 were
      improved. When GOD/CAT@IO-SiO2 was used to remove glucose from commercial
      isomaltooligosaccharide (IMO), the immobilized bi-enzyme system exhibited the
      good performance. The removal efficiency of glucose reached up to 98.97% under
      the conditions of GOD/CAT activity ratio of 1:30, the amount of enzyme of 68.8mg,
      reaction time of 9.39h, reaction temperature of 35.2 degrees C and pH of 7.05.
      After reused 6 times, 79.19% of removal efficiency could be still retained. The
      present work demonstrates that the immobilized bi-enzyme (GOD/CAT@IO-SiO2) is not
      only a very promising system for glucose removal but also has great potential for
      applications in production of gluconic acid, preparation of biosensors, enzyme
      bioreactors, etc.

PMID- 29051101
TI  - Molecular characterization and bioinformatics studies of a lipase from Bacillus
      thermoamylovorans BHK67.
AB  - A bacterium isolated from a hot-water spring identified as Bacillus
      thermoamylovorans BHK67 successfully produced a thermotolerant extracellular
      alkaliphilic lipase. The lipase was purified to homogeneity by anion exchange
      chromatography with 15-fold purification and 12.1% yield. The lipase appeared to
      be a hexameric protein as it possessed a single band of Mr 25kDa in SDS PAGE and
      150kDa in Native PAGE. DLS analysis of purified Bacillus thermoamylovorans BHK67
      lipase (BTL) also showed the molecular integrity, homogeneity and stability of
      the enzyme. The purified lipase showed maximum activity at pH 7.5 with a half
      life of 10.5h at 55 degrees C. Kinetic study of purified lipase by Lineweaver
      Burk plot provided Km (7.7mM),Vmax (90.9U/mL/min),Kcat (227.3s-1) and Kspec
      (29.4mMs-1) for substrate p-nitrophenylpalmitate.The purified lipase also showed
      astonishing stability following exposure to ethanol, n-propanol, iso-propanol, n
      butanol and DMSO. Amino acid characterization of BTL by MALDI-TOF-MS showed
      considerable resemblance with lysophospholipase L1 related esterase of
      Lactobacillus ozensis DSM 23829. Experimental coupled molecular modeling
      postulated a structure-activity correlation of BTL as a probable contender in
      degradation of xenobiotic compounds, biocatalysis, biotransformation of
      compounds, synthesis of optically active compounds, foodstuff industry,
      anticancer therapeutics etc.

PMID- 29051102
TI  - Isolation, structural characterization and bioactivities of naturally occurring
      polysaccharide-polyphenolic conjugates from medicinal plants-A reivew.
AB  - In recent years, several medicinal plants have been demonstrated as valuable
      resources of naturally occurring polysaccharide-polyphenolic conjugates. For the
      first time, this article introduces recent advances of polysaccharide
      polyphenolic conjugates isolated from different medicinal plants. The isolation,
      purification, structural characterization and biological activities of
      polysaccharide-polyphenolic conjugates are introduced in details. In general,
      polysaccharide-polyphenolic conjugates can be isolated by hot water or alkaline
      extraction followed by purification through anion exchange chromatography or gel
      filtration chromatography. The structures of conjugates are usually characterized
      by chemical composition analysis, UV-vis, Fourier-transform infrared and nuclear
      magnetic resonance spectroscopy. Moreover, polysaccharide-polyphenolic conjugates
      exhibit several biological activities including anticoagulant, antioxidant,
      radioprotective, anti-platelet, antitussive and bronchodilatory effects.
      Therefore, polysaccharide-polyphenolic conjugates isolated from medicinal plants
      are certain to have a bright prospect in the field of food and pharmaceutics.

PMID- 29051103
TI  - Silk-sericin degummed wastewater solution-derived and nitrogen enriched porous
      carbon nanosheets for robust biological imaging of stem cells.
AB  - Appreciated raw materials like silk-sericin can be recovered from silk-textile
      industrial waste for the production of novel functional nanomaterials. In this
      study, highly fluorescent sericin based carbon nanosheets (SCN) were produced
      from industrial wastewater containing silk-sericin as a precursor, and was
      applied as bio-imaging application for oral fat stem cells. A simple one-pot,
      hydrothermal carbonization method was used to produce SCN at a 180 degrees C. The
      obtained hydrothermal carbons exhibited strong fluorescence properties due to the
      presence of strong polar groups, such as carboxyl, amino and amide groups in the
      surface. Heteroatom functionalization of the SCN leads to the property of
      fluorescence due to enriched nitrogen and was confirmed by X-ray photoelectron
      and Fourier transform infrared spectroscopy. The plate-like morphology of SCN
      about 35nm in size was evaluated by transmission electron microscopy. The carbon
      13 nuclear magnetic resonance results revealed that nano-sized fluorescent SCN
      formed during carbonization and functionalization occurred through dehydration of
      the sericin protein. Moreover, the prepared SCNs demonstrated low toxicity and
      their suitability for bio-imaging applications was demonstrated to the oral fat
      stem cells. Overall, sericin degumming wastewater from the silk textile industry
      can be utilized for the production of SCNs for stem cells bio-imaging
      applications.

PMID- 29051104
TI  - Cross reactivity and lethality neutralization of venoms of Indonesian
      Trimeresurus complex species by Thai Green Pit Viper Antivenom.
AB  - Arboreal pit vipers of the Trimeresurus complex group are medically important
      species in Indonesia (west of Wallace's line), but there is no specific antivenom
      produced in the country for treating related envenomation. Instead, the exiting
      trivalent Indonesian antivenom, Biosave(r) Serum Anti Bisa Ular (SABU, indicated
      for envenoming by Malayan pit viper, Javan spitting cobra and banded krait) is
      often misused to treat Trimeresus envenoming resulting in poor therapeutic
      outcome. Here, we investigated the cross-reactivity and neutralization capability
      of Thai Green Pit Viper Antivenom (GPVAV) against the venoms of four Indonesian
      Trimeresurus species. Consistently, the venoms of Trimeresurus (Trimeresurus)
      insularis, Trimeresurus (Trimeresurus) purpureomaculatus, Trimeresurus (Parias)
      hageni and Trimeresurus (Craspedocephalus) puniceus of Indonesia showed stronger
      immunoreactivity on ELISA to GPVAV than to Biosave(r). The findings correlated
      with in vivo neutralization results, whereby GPVAV was far more effective than
      Biosave(r) in cross-neutralizing the lethality of the venoms by a potency of at
      least 13 to 80 times higher. The efficacy of GPVAV is partly attributable to its
      cross-neutralization of the procoagulant effect of the venoms, thereby mitigating
      the progression of venom-induced consumptive coagulopathy. The paraspecific
      effectiveness of GPVAV against Trimeresurus species envenoming in Indonesia await
      further clinical investigation.

PMID- 29051105
TI  - Nicotine and autoimmunity: The lotus' flower in tobacco.
AB  - Nicotine, the major component of cigarettes, has demonstrated conflicting impact
      on the immune system: some authors suggest that increases pro-inflammatory
      cytokines and provokes cellular apoptosis of neutrophils, releasing intracellular
      components that act as auto-antigens; others claimed that nicotine has a
      protective and anti-inflammatory effects, especially by binding to alpha7 subunit
      of nicotinic acetylcholine receptors. The cholinergic pathway contributes to an
      anti-inflammatory environment characterized by increasing T regulatory cells
      response, down-regulating of pro-inflammatory cytokines and a pro-inflammatory
      cells apoptosis. The effects of nicotine were studied in different autoimmune
      disease, as multiple sclerosis, type 1 diabetes, rheumatoid arthritis,
      sarcoidosis, Behcet's disease and inflammatory bowel diseases. The major problems
      about nicotine are the addiction and the adverse effects of related to each
      commercialized formulation. We sought in this review to summarize the knowledge
      accumulated to date concerning the relationship between nicotine and
      autoimmunity.

PMID- 29051106
TI  - Can teamwork and situational awareness (SA) in ED resuscitations be improved with
      a technological cognitive aid? Design and a pilot study of a team situation
      display.
AB  - : Effective teamwork in ED resuscitations, including information sharing and
      situational awareness, could be degraded. Technological cognitive aids can
      facilitate effective teamwork. OBJECTIVE: This study focused on the design of an
      ED situation display and pilot test its influence on teamwork and situational
      awareness during simulated resuscitation scenarios. MATERIAL AND METHODS: The
      display design consisted of a central area showing the critical dynamic
      parameters of the interventions with an events time-line below it. Static
      information was placed at the sides of the display. We pilot tested whether the
      situation display could lead to higher scores on the Clinical Teamwork Scale
      (CTS), improved scores on a context-specific Situational Awareness Global
      Assessment Technique (SAGAT) tool, and team communication patterns that reflect
      teamwork and situational awareness. RESULTS: Resuscitation teamwork, as measured
      by the CTS, was overall better with the presence of the situation display as
      compared with no situation display. Team members discussed interventions more
      with the situation display compared with not having the situation display.
      Situational awareness was better with the situation display only in the trauma
      scenario. DISCUSSION: The situation display could be more effective for certain
      ED team members and in certain cases. CONCLUSIONS: Overall, this pilot study
      implies that a situation display could facilitate better teamwork and team
      communication in the resuscitation event.

PMID- 29051107
TI  - Advances in the GRADE approach to rate the certainty in estimates from a network
      meta-analysis.
AB  - This article describes conceptual advances of the Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) working group guidance to
      evaluate the certainty of evidence (confidence in evidence, quality of evidence)
      from network meta-analysis (NMA). Application of the original GRADE guidance,
      published in 2014, in a number of NMAs has resulted in advances that strengthen
      its conceptual basis and make the process more efficient. This guidance will be
      useful for systematic review authors who aim to assess the certainty of all
      pairwise comparisons from an NMA and who are familiar with the basic concepts of
      NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles
      of the original GRADE NMA guidance are that we need to rate the certainty of the
      evidence for each pairwise comparison within a network separately and that in
      doing so we need to consider both the direct and indirect evidence. We present,
      discuss, and illustrate four conceptual advances: (1) consideration of
      imprecision is not necessary when rating the direct and indirect estimates to
      inform the rating of NMA estimates, (2) there is no need to rate the indirect
      evidence when the certainty of the direct evidence is high and the contribution
      of the direct evidence to the network estimate is at least as great as that of
      the indirect evidence, (3) we should not trust a statistical test of global
      incoherence of the network to assess incoherence at the pairwise comparison
      level, and (4) in the presence of incoherence between direct and indirect
      evidence, the certainty of the evidence of each estimate can help decide which
      estimate to believe.

PMID- 29051108
TI  - A Bayesian model that jointly considers comparative effectiveness research and
      patients' preferences may help inform GRADE recommendations: an application to
      rheumatoid arthritis treatment recommendations.
AB  - OBJECTIVES: The objective of the study was to estimate the preferred treatment
      for early rheumatoid arthritis using a novel Bayesian approach that jointly
      considers patients' preferences and comparative effectiveness research. STUDY
      DESIGN AND SETTING: We estimated the preferred treatment using patients'
      preferences measured in a discrete-choice experiment to apply weights to benefit
      and harm outcomes from a network meta-analysis and other considerations (dosing,
      rare adverse events). Using Bayesian analyses, we considered the variability in
      patients' preferences and the imprecision in both patients' preferences and the
      treatment effects; all key considerations in the Grading of Recommendations
      Assessment, Development, and Evaluation approach. RESULTS: We estimated that most
      patients in our population would prefer triple therapy as initial treatment (78%)
      or after an inadequate response to methotrexate (62%). The probability of
      choosing triple therapy as initial treatment was further from 50% (the point of
      indifference) for more patients, making our prediction more confident, and
      suggesting a stronger recommendation could be made. After an inadequate response
      to methotrexate, the choice was more split, suggesting a decision aid may be
      helpful. CONCLUSION: Using a novel approach, we estimated that many patients with
      early rheumatoid arthritis may prefer triple therapy to other treatment options,
      in contrast to existing guidelines. This offers an approach that may help inform
      Grading of Recommendations Assessment, Development, and Evaluation treatment
      recommendations.

PMID- 29051109
TI  - Spontaneous Intrauterine Depressed Skull Fractures: Report of 2 Cases Requiring
      Neurosurgical Intervention and Literature Review.
AB  - BACKGROUND: Spontaneous intrauterine depressed skull fractures (IDSFs) are rare
      fractures that often require neurosurgical evaluation and therapy. Most of the
      reported congenital depressions are secondary to maternal abdominal trauma or
      instrumentation during delivery. Spontaneous IDSFs occur in the setting of
      uneventful normal spontaneous vaginal delivery or cesarean section, without
      obvious predisposing risk factors. The etiology and optimal management of
      spontaneous IDSFs remain controversial. CASE DESCRIPTION: We describe 2 cases of
      spontaneous IDSF who underwent cranioplasty at our institution using an
      absorbable mesh, as well as review the current state of knowledge regarding the
      diagnosis and management of spontaneous IDSF. The 2 neonates, 1 male and 1
      female, presented at Lucile Packard Children's Hospital with spontaneous IDSF
      after uneventful normal spontaneous vaginal deliveries. The fractures were
      located in the left frontal and right parietotemporal calvarium, respectively.
      Both patients underwent open craniotomy and elevation of their IDSFs with mesh
      cranioplasty. At last follow-up, both patients were normocephalic and
      neurologically intact. CONCLUSIONS: Neurosurgery consultation is necessary for
      initial evaluation of spontaneous IDSF. Surgical intervention is indicated for
      larger defects and/or intracranial involvement. Expectant management and negative
      pressure elevation have also been shown to be effective.

PMID- 29051110
TI  - The Extracranial Consequences of Subarachnoid Hemorrhage.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) is managed across the full spectrum of
      healthcare, from clinical diagnosis to management of the hemorrhage and
      associated complications. Knowledge of the pathogenesis and pathophysiology of
      SAH is widely known; however, a full understanding of the underlying molecular,
      cellular, and circulatory dynamics has still to be achieved. Intracranial
      complications including delayed ischemic neurologic deficit (vasospasm), rebleed,
      and hydrocephalus form the targets for initial management. However, the
      extracranial consequences including hypertension, hyponatremia, and
      cardiopulmonary abnormalities can frequently arise during the management phase
      and have shown to directly affect clinical outcome. This review will provide an
      update on the pathophysiology of SAH, including the intra- and extracranial
      consequences, with a particular focus on the extracranial consequences of SAH.
      METHODS: We review the literature and provide a comprehensive update on the
      extracranial consequences of SAH that we hope will help the management of these
      cohort of patients. RESULTS: In addition to the pathophysiology of SAH, the
      following complications were examined and discussed: vasospasm, seizures,
      rebleed, hydrocephalus, fever, anemia, hypertension, hypotension, hyperglycemia,
      hyponatremia, hypernatremia, cardiac abnormalities, pulmonary edema, venous
      thromboembolism, gastric ulceration, nosocomial infection, bloodstream
      infection/sepsis, and iatrogenic complications. CONCLUSIONS: Although the
      intracranial complications of SAH can take priority in the initial management,
      the extracranial complications should be monitored for and recognized as early as
      possible because these complications can develop at varying times throughout the
      course of the condition. Therefore, a variety of investigations, as described by
      this article, should be undertaken on admission to maximize early recognition of
      any of the extracranial consequences. Furthermore, because the extracranial
      complications have a direct effect on clinical outcome and can lead to and
      exacerbate the intracranial complications, monitoring, recognizing, and managing
      these complications in parallel with the intracranial complications is important
      and would allow optimization of the patient's management and thus help improve
      their overall outcome.

PMID- 29051111
TI  - Perspectives on using a multiplex human kidney safety biomarker panel to detect
      cisplatin-induced tubular toxicity in male and female Cynomolgus monkeys.
AB  - Multiplex biomarker panel assays would enable early de-risking of discovery
      compound related kidney safety liabilities. The objective of this study was to
      evaluate the usefulness of the Myriad RBM Human KidneyMAP (Multi-Analyte
      Profile)(r) v.1.0 panel to detect experimental nephrotoxicity in Cynomolgus
      monkeys following a single intravenous administration of cisplatin (2.5mg/kg).
      Urine samples were collected at baseline on day -2; at approximately 4hr post
      dose on day 1; and on days 4, 9, 15 and/or 20. Blood samples were collected at
      predose on day -2; at 4hr post-dose on day 1; and on days 2, 5, 10 and/or 21.
      Changes in toxicokinetic and biochemistry parameters in plasma,
      qualitative/quantitative urinalysis parameters, and urinary kidney safety
      biomarkers were assessed. Kidney tissues were collected on days 2, 5, 10 and 21
      for routine microscopy. Cisplatin-induced tubular alterations were characterized
      by acute and progressive cortical tubular degeneration/necrosis, regeneration,
      tubular dilation and proteinaceous cast in the absence of statistically
      significant changes in traditional plasma biochemistry and urinalysis parameters.
      When normalized to urinary creatinine, cisplatin-induced significant increases in
      urinary levels of kidney injury molecule 1 (females on day 4), increases in
      calbindin D28k (males and females on day 4), decreases in Tamm-Horsfall
      glycoprotein (males on days 1, 4 and 9), and increases in clusterin (females and
      males on days 15 and 20, respectively), when compared to concurrent controls.
      This study revealed the usefulness of the Human KidneyMAP(r) multiplex panel when
      measuring changes in urine-based biomarkers to reliably detect cisplatin-induced
      acute/progressive cortical tubular injury in male and female Cynomolgus monkeys.

PMID- 29051112
TI  - In vivo and in silico evaluation of a new nitric oxide donor, S,S'
      dinitrosobucillamine.
AB  - PURPOSE: In a previous work, we have synthetized a new dinitrosothiol, i.e. S,S'
      dinitrosobucillamine BUC(NO)2 combining S-nitroso-N-acetylpenicillamine (SNAP)
      and S-nitroso-N-acetylcysteine (NACNO) in its structure. When exposed to isolated
      aorta, we observed a 1.5-fold increase of *NO content and a more potent
      vasorelaxation (1 log higher pD2) compared to NACNO and SNAP alone or combined
      (Dahboul et al., 2014). In the present study, we analyzed the thermodynamics and
      kinetics for the release of *NO through computational modeling techniques and
      correlated it to plasma assays. Then BUC(NO)2 was administered in vivo to rats,
      assuming it will induce higher and/or longer hypotensive effects than its two
      constitutive S-mononitrosothiols. METHODS: Free energies for the release of *NO
      entities have been computed at the density functional theory level assuming an
      implicit model for the aqueous environment. Degradation products of BUC(NO)2 were
      evaluated in vitro under heating and oxidizing conditions using HPLC coupled with
      tandem mass spectrometry (MS/MS). Plasma from rats were spiked with RSNO and
      kinetics of RSNO degradation was measured using the classical Griess-Saville
      method. Blood pressure was measured in awake male Wistar rats using telemetry (n
      = 5, each as its own control, 48 h wash-out periods between subcutaneous
      injections under transient isoflurane anesthesia, random order: 7 mL/kg vehicle,
      3.5, 7, 14 MUmol/kg SNAP, NACNO, BUC(NO)2 and an equimolar mixture of SNAP +
      NACNO in order to mimic the number of *NO contained in BUC(NO)2). Variations of
      mean (DeltaMAP, reflecting arterial dilation) and pulse arterial pressures
      (DeltaPAP, indirectly reflecting venodilation, used to determine effect duration)
      vs. baseline were recorded for 4 h. RESULTS: Computational modeling highlights
      the fact that the release of the first *NO radical in BUC(NO)2 requires a free
      energy which is intermediate between the values obtained for SNAP and NACNO.
      However, the release of the second *NO radical is significantly favored by the
      concerted formation of an intramolecular disulfide bond. The corresponding
      oxidized compound was also characterized as related substance obtained under
      degradation conditions. The in vitro degradation rate of BUC(NO)2 was
      significantly greater than for the other RSNO. For equivalent low and medium *NO
      load, BUC(NO)2 produced a hypotension identical to NACNO, SNAP and the equimolar
      mixture of SNAP + NACNO, but its effect was greater at higher doses (-62 +/- 8
      and -47 +/- 14 mmHg, maximum DeltaMAP for BUC(NO)2 and SNAP + NACNO,
      respectively). Its duration of effect on PAP (-50%) lasted from 35 to 95 min,
      i.e. shorter than for the other RSNO (from 90 to 135 min for the mixture SNAP +
      NACNO). CONCLUSION: A faster metabolism explains the abilities of BUC(NO)2 to
      release higher amounts of *NO and to induce larger hypotension but shorter
      lasting effects than those induced by the SNAP + NACNO mixture, despite an
      equivalent *NO-load.

PMID- 29051113
TI  - Body Composition Early Identifies Cancer Patients With Radiotherapy at Risk for
      Malnutrition.
AB  - CONTEXT: The side effects of radiotherapy (RT) and the occurrence of comorbidity
      often result in appetite loss in patients, which leads to serious nutritional
      problems, significantly affecting the patients' treatment results and disease
      prognosis. OBJECTIVES: We aimed to investigate changes in the body composition of
      patients with cancer from the time they received RT to three months after
      completion of RT. METHODS: A total of 101 cancer patients who received RT, which
      included head or neck cancer, chest or breast cancer, and abdominal or pelvic
      cancer patients, were recruited. A longitudinal study design was adopted, in
      which the body composition analyzer In Body3.0 was used to obtain patient data at
      six different time points. The data were analyzed through generalized estimating
      equation. RESULTS: All patients with cancer had the lowest body mass index at the
      end of RT. For head or neck cancer patients, their total body water and muscle
      mass decreased significantly in the fourth week of RT and at the end of RT. For
      chest or breast cancer patients, their body fat mass changed significantly in the
      second and fourth weeks of RT (beta = -0.57, P = 0.0233; beta = -3.23, P =
      0.0254). For abdominal or pelvic cancer patients, their total body weight and
      muscle mass decreased significantly in the second week of RT and at the end of RT
      (beta = -1.07, P = 0.0248; beta = -5.13, P = 0.0017; beta = -1.37, P = 0.0245;
      beta = -6.50, P = 0.0016); their body fat mass increased significantly in the
      third month after RT (beta = 4.61, P = 0.0072). CONCLUSION: Body composition
      analysis can be used to promptly and effectively monitor changes in the
      nutritional status of patients with cancer during the cancer treatment period;
      changes in the body composition at different repetitions differ between patients
      with dissimilar cancers.

PMID- 29051115
TI  - An herbal formula consisting of Schisandra chinensis (Turcz.) Baill, Lycium
      chinense Mill and Eucommia ulmoides Oliv alleviates disuse muscle atrophy in
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (SC), Lycium
      chinense Mill (LC) and Eucommia ulmoides Oliv (EU) are representative tonic
      herbal medicines that help to strengthen body muscles and bones making them
      stronger according to the Donguibogam, a tradition medical book of the Joseon
      Dynasty in Korea. AIM OF THE STUDY: To evaluate effects of an herbal formula
      consisting of SC, LC and EU on muscle atrophy in C2C12 myotubes and in a rat
      model of immobilization-induced muscle atrophy. MATERIALS AND METHODS: Muscle
      atrophy was developed by cast immobilization of unilateral hindlimb on rats for 3
      weeks. Treatments were administered orally 14 times over 3 weeks. After
      treatments, we compared the change of body weight, muscle weight, grip strength,
      muscle fiber size, muscle fiber type shift by Grip strength meter, H&E stain and
      ATPase stain. And western blot was used for evaluating molecular mechanism in
      muscle atrophy on C2C12 cells. RESULTS: When taken individually, SC was the most
      effective of the three in inhibiting tumor necrosis factor alpha (TNF-alpha)
      induced degeneration of C2C12 myogenesis. The formulation with a mass ratio of
      2:1:1 SC: LC: EU (SSLE) was more effective against TNF-alpha-induced muscle
      atrophy than was a 1:1:1 SC: LC: EU (SLE) formula or any of the single herbal
      extracts. In a rat model of disuse muscle atrophy, the SSLE formula significantly
      inhibited reductions in muscle weight, grip strength and muscle fiber size
      induced by hindlimb immobilization, in a dose-dependent manner. The formula also
      inhibited immobilization-induced shifting of the muscle fiber type in soleus
      muscle. Treatment with SSLE inhibited TNF-alpha-induced expression of the
      atrogenes atrogin-1 and muscle RING-finger protein 1 in C2C12 cells. The SSLE
      formula also increased myoblast differentiation markers (myoD and myogenin) and
      activation of the Akt and mammalian target of rapamycin (mTOR) signaling pathway.
      CONCLUSION: These findings suggest that the SSLE formula prevents muscle atrophy
      through inhibition of the ubiquitin-proteasome system as well as upregulation of
      myoblast differentiation and muscle protein synthesis in C2C12 cells. Taken
      together, we conclude that the SSLE formula is invaluable for the development of
      therapeutic medicines to prevent disuse muscle atrophy and its accompanying
      muscle weakness.

PMID- 29051114
TI  - Changes in the Occurrence, Severity, and Distress of Symptoms in Patients With
      Gastrointestinal Cancers Receiving Chemotherapy.
AB  - CONTEXT: Studies on multiple dimensions of the symptom experience of patients
      with gastrointestinal cancers are extremely limited. OBJECTIVE: Purpose was to
      evaluate for changes over time in the occurrence, severity, and distress of seven
      common symptoms in these patients. METHODS: Patients completed Memorial Symptom
      Assessment Scale, six times over two cycles of chemotherapy (CTX). Changes over
      time in occurrence, severity, and distress of pain, lack of energy, nausea,
      feeling drowsy, difficulty sleeping, and change in the way food tastes were
      evaluated using multilevel regression analyses. In the conditional models,
      effects of treatment group (i.e., with or without targeted therapy), age, number
      of metastatic sites, time from cancer diagnosis, number of prior cancer
      treatments, cancer diagnosis, and CTX regimen on enrollment levels, as well as
      the trajectories of symptom occurrence, severity, and distress were evaluated.
      RESULTS: Although the occurrence rates for pain, lack of energy, feeling drowsy,
      difficulty sleeping, and change in the way food tastes declined over the two
      cycles of CTX, nausea and numbness/tingling in hands/feet had more complex
      patterns of occurrence. Severity and distress ratings for the seven symptoms
      varied across the two cycles of CTX. CONCLUSIONS: Demographic and clinical
      characteristics associated with differences in enrollment levels as well as
      changes over time in occurrence, severity, and distress of these seven common
      symptoms were highly variable. These findings can be used to identify patients
      who are at higher risk for more severe and distressing symptoms during CTX and to
      enable the initiation of preemptive symptom management interventions.

PMID- 29051116
TI  - Post-stroke rehabilitation devices offered via the Internet: Based on randomized
      controlled evidence?

PMID- 29051118
TI  - Sequential therapy with redox-responsive glucolipid nanocarrier separately
      delivering siRNA and doxorubicin to overcome multidrug resistance.
AB  - P-glycoprotein (P-gp) is a major efflux transporter overexpressed on multidrug
      resistant tumor cells and responsible for pumping drugs out. If anti-tumor drugs
      are given when P-gp level is low, satisfactory treatment efficiency may be
      achieved. Thus, a P-gp down-regulating siRNA (siMDR1) and doxorubicin (DOX) were
      applied to eliminate multidrug resistant breast cancer cells (MCF-7/ADR). A redox
      responsive glucolipid conjugate (CSO-ss-SA) was used to condense siRNA (CSO-ss
      SA/siRNA) and encapsulate DOX (CSO-ss-SA/DOX) separately. They responded to the
      high reducing environment of tumor cells and fast released the payload. CSO-ss
      SA/siMDR1 silenced MDR1 gene and resulted in a transient decrease of P-gp.
      Sequentially, DOX formulation (CSO-ss-SA/DOX or DOX.HCl) was delivered when P-gp
      was reduced to the lowest level. After pretreatment by CSO-ss-SA/siMDR1,
      cytotoxicity of CSO-ss-SA/DOX and DOX.HCl against MCF-7/ADR cells were 6.4 or 3.4
      fold respectively of that treated by DOX.HCl alone, which exhibited increased
      cytotoxin sensitivity of drug resistant cells and maximized therapeutic outcomes.
      These results revealed that the sequential treatment strategy of CSO-ss-SA/siRNA
      and CSO-ss-SA/DOX hold potential in achieving an optimal overcoming multidrug
      resistance efficiency.

PMID- 29051117
TI  - Melatonin reduces oxidative damage and upregulates heat shock protein 90
      expression in cryopreserved human semen.
AB  - Sperm cells can be damaged during the semen cryopreservation process, decreasing
      their fertilizing ability. Physical damage and oxidative stress may occur during
      the freeze-thawing process. Antioxidants such as the native antioxidant melatonin
      can potentially improve cryopreservation outcomes. In this study, we added
      melatonin to cryoprotectant to examine its effect on frozen-thawed human sperm.
      We found that adding 0.1mM melatonin to cryoprotectant significantly increased
      sperm viability (24.80 +/- 0.46% vs. 20.97 +/- 1.27%, P < 0.05) and membrane
      integrity (P < 0.05), and decreased intracellular reactive oxygen species and
      lipid peroxidation damage. Furthermore, mRNA levels of the transcription factor
      NF-E2-related factor-2 and its downstream genes were significantly increased.
      Resistance to oxidative stress was enhanced and expression of the antiapoptotic
      gene Bcl-2 was increased by inclusion of 0.1mM melatonin in the cryoprotectant.
      Moreover, 0.1mM melatonin upregulated the expression of heat shock protein 90
      (HSP90), which confers resistance to stressors in frozen-thawed sperm. Results
      obtained upon addition of inhibitors of melatonin receptors (luzindole and 4-P
      PDOT) and an HSP90 inhibitor (geldanamycin) in the cryoprotectant demonstrated
      that melatonin promoted HSP90 translation via the melatonin receptor MT1 and
      increased adenosine triphosphate levels, thus increasing the viability of thawed
      sperm.

PMID- 29051119
TI  - Novel dissolving microneedles for enhanced transdermal delivery of
      levonorgestrel: In vitro and in vivo characterization.
AB  - Dissolving microneedles (DMN) have been studied as a drug delivery system to
      enhance the transport of drug molecules across the skin with almost no pain.
      However, the poor dissolving ability of microneedles in the skin and low drug
      loading have limited their potential application. The aim of this study was to
      develop a novel dissolving microneedle system with improved dissolving ability
      for the delivery of poorly water soluble contraception drug, levonorgestrel
      (LNG). Chitosan and beta-sodium glycerophosphate (beta-GP) were incorporated in
      the formulation of microneedles. It was found that 69.32+/-4.23% of the
      microneedles penetrated through the skin and dissolved within the first 2h, which
      was almost 2-fold higher than that of the conventional microneedles. In addition,
      drug loading was significantly increased by packaging LNG into the molecules of
      hydroxypropyl beta cyclodextrin (HP-beta-CD) to form LNG-HP-beta-CD inclusion
      compounds. The use of chitosan and beta-GP together with HP-beta-CD inclusion
      compounds was shown to enhance the bioavailability of LNG transdermally. This
      novel DMN system resulted in a similar pharmacokinetic profile as that following
      oral administration. In addition to similar Cmax and AUC values, drug
      concentrations in the blood were more consistent following the DMN in comparison
      to oral administration.

PMID- 29051120
TI  - The influence of high shear mixing on ternary dry powder inhaler formulations.
AB  - The blending process is a key step in the production of dry powder inhaler
      formulations, but only little is known about the influence of process parameters.
      This is especially true for high shear blending of ternary formulations. For this
      reason, this study aims to investigate the influence of high shear mixing process
      parameters (mixing time and rotation speed) on the fine particle fraction (FPF)
      of ternary mixtures when using budesonide as model drug, two different carrier
      materials and two different mixing orders. Prolonged mixing time and higher
      rotation speeds led to lower FPFs, possibly due to higher press-on forces acting
      on the active pharmaceutical ingredients (API). In addition, a clear correlation
      between the energy consumption of the blender (the energy input into the blend)
      and the reduction of the FPF could be shown. Furthermore blending the carrier and
      the fines before adding the API was also found to be favorable.

PMID- 29051121
TI  - Preparation and investigation of novel gastro-floating tablets with 3D extrusion
      based printing.
AB  - Three dimensional (3D) extrusion-based printing is a paste-based rapid
      prototyping process, which is capable of building complex 3D structures. The aim
      of this study was to explore the feasibility of 3D extrusion-based printing as a
      pharmaceutical manufacture technique for the fabrication of gastro-floating
      tablets. Novel low-density lattice internal structure gastro-floating tablets of
      dipyridamole were developed to prolong the gastric residence time in order to
      improve drug release rate and consequently, improve bioavailability and
      therapeutic efficacy. Excipients commonly employed in the pharmaceutical study
      could be efficiently applied in the room temperature 3D extrusion-based printing
      process. The tablets were designed with three kinds of infill percentage and
      prepared by hydroxypropyl methylcellulose (HPMC K4M) and hydroxypropyl
      methylcellulose (HPMC E15) as hydrophilic matrices and microcrystalline cellulose
      (MCC PH101) as extrusion molding agent. In vitro evaluation of the 3D printed
      gastro-floating tablets was performed by determining mechanical properties,
      content uniformity, and weight variation. Furthermore, re-floating ability,
      floating duration time, and drug release behavior were also evaluated.
      Dissolution profiles revealed the relationship between infill percentage and drug
      release behavior. The results of this study revealed the potential of 3D
      extrusion-based printing to fabricate gastro-floating tablets with more than 8h
      floating process with traditional pharmaceutical excipients and lattice internal
      structure design.

PMID- 29051122
TI  - Photodynamic therapy leads to significant improvement of actinic keratosis area
      and severity index (AKASI).
AB  - BACKGROUND: Actinic keratosis area and severity index (AKASI) is a new
      quantitative tool for assessing AK severity on the head and can be used to
      monitor outcomes of different therapies. The aim of this study was to determine
      treatment outcomes of AK applying AKASI three months after conventional
      photodynamic therapy (PDT). METHODS: We performed a retrospective analysis of
      patients who have undergone PDT on the head and had a documented AKASI evaluation
      prior to PDT and at follow-up visits. RESULTS: Of the 33 patients included, 32
      (97.0%) patients showed an AKASI reduction and 1 (3.0%) patient an increase of
      AKASI at follow-up visits compared to baseline. The median (range) follow-up
      period was 96days (70-161). The median difference of AKASI values between both
      visits was 73.7% (-34.8 to 100.0%). The Wilcoxon test showed highly significant
      differences (P<0.0001) between visits. 14 (42.4%) patients showed an AKASI 100
      (complete clearance), 16 (48.5%) an AKASI 75 and 24 (72.7%) an AKASI 50,
      respectively. The Mann-Whitney U test showed in a subgroup analysis of patients
      with a positive history of at least more than one intervention and treatment
      naive patients significant differences in these two groups (P=0.0302).
      CONCLUSIONS: AKASI represents a feasible and comparable tool for objectively
      assessing field-directed treatment modalities such as PDT in daily routine. The
      establishment of AKASI 50, 75, 100 serves as an objective measure to compare
      treatment outcomes to baseline severity of AK.

PMID- 29051123
TI  - Knowledge, behavior and attitudes of dental practitioners towards photodynamic
      therapy use in dental practice.
AB  - BACKGROUND: The aim of the present study was to assess knowledge, behavior and
      attitudes of dental practitioners (DPs) towards photodynamic therapy (PDT) in
      dental clinical practice. METHODS: A cross-sectional study was performed and a 13
      item survey questionnaire was given to DPs practicing in 13 different teaching
      hospitals in Karachi, Pakistan. Questions were aimed at exploring the knowledge
      of DPs regarding PDT and their attitude towards PDT and perceptions that may
      influence clinical practices. Chi-square and spearman coefficient were conducted
      to compare subgroups and correlate factors with the knowledge score of DPs.
      RESULTS: A total of 509 questionnaires were completed (response rate=82%). Median
      age of participants was 34 years and 70% were females. Most DPs demonstrated good
      knowledge related to PDT, and nearly 77%, 69% and 62% were aware of the mechanism
      of action and the role of photosensitizers in PDT respectively. It was reported
      that 74% of the respondents expressed that they are comfortable to know about PDT
      in detail for their clinical practice. A cumulative 54% disagreed that discussing
      the option for PDT with their patients was peripheral to their role as
      clinicians. A striking 82% would like to attend seminars and workshops on PDT.
      Significant difference was found among senior lecturers and assistant professors
      for the knowledge items (p <0.05). No statistical correlation was found between
      the knowledge items score of DPs and their behavior (r=0.18; p=0.762), attitude
      (r=0.04; p=0.594) and self-rated knowledge (r=0.42; p=0.854). CONCLUSION: Dental
      practitioners showed adequate knowledge regarding PDT and its use in dentistry.
      However, expertise with regards to handling and training is warranted so that DPs
      could use PDT in their dental practice.

PMID- 29051124
TI  - ESC Congress 2017 - what did we learn?

PMID- 29051125
TI  - Transcatheter aortic valve implantation - practice makes perfect.

PMID- 29051126
TI  - Resistance to flow in the coronary microcirculation - we can measure it but what
      does it mean?

PMID- 29051127
TI  - Acute ischaemic stroke in atrial fibrillation: worse outcomes unrelated to
      treatment methods.

PMID- 29051128
TI  - Day case TAVI: is this a reality?

PMID- 29051130
TI  - Concerns about left atrial appendage occlusion.

PMID- 29051131
TI  - Left atrial appendage occlusion is promising, not concerning.

PMID- 29051132
TI  - How should I treat a rupture of the interatrial septum with haemodynamically
      relevant right-to-left shunt during MitraClip implantation?

PMID- 29051133
TI  - Experiences From a Web- and App-Based Workplace Health Promotion Intervention
      Among Employees in the Social and Health Care Sector Based on Use-Data and
      Qualitative Interviews.
AB  - BACKGROUND: An increasing number of Web- and app-based tools for health promotion
      are being developed at the moment. The ambition is generally to reach out to a
      larger part of the population and to help users improve their lifestyle and
      develop healthier habits, and thereby improve their health status. However, the
      positive effects are generally modest. To understand why the effects are modest,
      further investigation into the participants' experiences and the social aspects
      of using Web- and app-based health promotion tools is needed. OBJECTIVE: The
      objectives of this study were to investigate the motivation behind taking part in
      and using a Web- and app-based health promotion tool (SoSu-life) at the workplace
      and to explore the participants' experiences with using the tool. METHODS:
      Qualitative interviews with 26 participants who participated in a 38-week
      randomized controlled trial of a workplace Web- and app-based tool for health
      promotion were conducted. Data were supplemented with tracking the frequency of
      use. The basic features of the tool investigated in the trial were self-reporting
      of diet and exercise, personalized feedback, suggestions for activities and
      programs, practical tips and tricks, and a series of social features designed to
      support and build interactions among the participants at the workplace. RESULTS:
      The respondents reported typically one of the two reasons for signing up to
      participate in the study: either a personal wish to attain some health benefits
      or the more social reason that participants did not want to miss out on the
      social interaction with colleagues. Peer pressure from colleagues had made some
      participants to sign up even though they did not believe they had an unhealthy
      behavior. Of the total of 355 participants in the intervention group, 203 (57.2%)
      left the intervention before it ended. Of the remaining participants, most did
      not use the tool after the competition at the end of the initial 16-week period.
      The actual number of active users of the tool throughout the whole intervention
      period was low; however, the participants reported that lifestyle habits became a
      topic of conversation. CONCLUSIONS: A tool that addresses group interactions at
      workplaces appears to initiate peer pressure, which helped recruitment for
      participation. However, active participation was low. A social change was
      indicated, allowing for more interaction among colleagues around healthy
      lifestyle issues. Future and more long-term studies are needed to determine
      whether such social changes could lead to sustained improvements of health.

PMID- 29051134
TI  - A Telerehabilitation Approach to Enhance Quality of Life Through Exercise Among
      Adults With Paraplegia: Study Protocol.
AB  - BACKGROUND: Despite compelling evidence linking physical activity and quality of
      life among adults with spinal cord injury (SCI), exercise participation rates are
      extremely low in this population. Unfortunately, a lack of behavioral exercise
      interventions, in particular theory-based randomized controlled trials (RCT),
      exists within the SCI literature. A pilot RCT is needed to first examine the
      feasibility to conduct such interventions and determine the appropriate effect
      size to inform future full-scale interventions. OBJECTIVE: The overall goal of
      this pilot RCT is to test an 8-week innovative, video-based telerehabilitation
      intervention based on self-determination theory and aimed at enhancing the basic
      psychological needs, motivation, exercise participation, and quality of life
      related outcomes of adults with paraplegia. The objectives are to (1) determine
      if individuals in the intervention group have greater increases in their basic
      psychological needs and autonomous motivation and a decrease in controlled
      motivation compared to the control group, (2) determine whether the intervention
      group reports greater increases in exercise participation and quality of life
      related variables (eg, life satisfaction, participation in daily/social
      activities, depressive symptoms) compared to the control group, and (3) examine
      if adults with paraplegia who received the intervention report improved scores on
      psychosocial predictors of exercise (eg, action planning) and well-being (eg,
      positive affect) compared to the control group. We also aimed to examine the
      implementation characteristics of the intervention (eg, satisfaction with the
      technology, counselor's ability to foster the psychological needs). METHODS:
      Adults with paraplegia (N=24) living in the community will be recruited. All
      participants will be invited to complete assessments of their psychological
      needs, motivation, exercise, and quality of life-related variables at three time
      points (baseline, 6, and 10 weeks). Following the baseline assessment,
      participants will be randomly assigned to the intervention or control group.
      Participants in the intervention group will participate in 8 weekly, 1-hour video
      based telerehabilitation sessions with a trained physical activity counselor,
      while participants in the control group will be asked to continue with their
      regular routine. RESULTS: We expect higher ratings of the basic psychological
      needs and autonomous motivation and lower scores for controlled motivation for
      the intervention group compared to the control group (Objective 1). We also
      expect that our video-based intervention will have moderate effects on exercise
      participation, as well as small-to-moderate positive effects on the quality of
      life-related variables (Objective 2). Finally, we expect the intervention to have
      a small positive effect on psychosocial predictors of physical activity and well
      being (Objective 3). CONCLUSIONS: We anticipate that the results will show that
      the intervention is appropriate for adults with paraplegia and feasible to test
      in a full-scale RCT. TRIAL REGISTRATION: ClinicalTrials.gov NCT02833935;
      https://clinicaltrials.gov/ct2/show/NCT02833935 (Archived by WebCite at
      http://www.webcitation.org/6u8U9x2yt).

PMID- 29051135
TI  - A Transmedia Storytelling Intervention With Interactive Elements to Benefit
      Latinas' Mental Health: Feasibility, Acceptability, and Efficacy.
AB  - BACKGROUND: Latinos report higher rates of depression and anxiety than US whites
      but are less likely to receive care. Transmedia storytelling interventions
      accessible on the Internet via smartphones, tablets, and computers hold promise
      for reducing reluctance to explore or get help for symptoms because they are
      private, convenient, and can reach large numbers of people, including Latinas
      with mental health needs. OBJECTIVE: The purpose of this study was to examine the
      feasibility, acceptability, and preliminary efficacy of a mental health
      transmedia intervention for Latinas with elevated symptoms of depression,
      anxiety, or both. METHODS: A total of 28 symptomatic English-speaking Latina
      women aged 21 to 48 years participated in a 6-week study using a within-group
      design. All aspects of the study were completed via telephone or Internet.
      Participants used their personal devices to engage the Web-based transmedia
      intervention (in English) that included story-based videos, a data-informed
      psychotherapeutic video, an interactive video sequence, and a blog written from
      the point of view of one of the characters with links to mental health resources.
      Perceived confidence to get help and perceived importance for seeking immediate
      help were both measured using single-item questions. Participants completed
      surveys at baseline (via telephone) and 1 and 6 weeks after media engagement that
      measured various factors, including depression (Patient Health Questionnaire; PHQ
      9 and PHQ-8) and anxiety (Generalized Anxiety Disorder scale; GAD-7). A telephone
      interview was conducted within 72 hours of media engagement. Action taken or
      intentions to get help (single-item question) and talking about the videos with
      others (single-item question) were measured 1 and 6 weeks after media engagement.
      Repeated measures analysis of variance was used to assess change in depression
      (PHQ-8) and anxiety (GAD-7) before transmedia engagement and 1 and 6 weeks after.
      Spearman correlations evaluated the association of confidence and importance of
      getting help with action taken, anxiety, and depression. RESULTS: All 28 Latinas
      (English speakers) who engaged with the transmedia remained in the 6-week study.
      Within 1 week of transmedia engagement, 39% of women took action to get help, and
      82% discussed the media with others. Symptoms of depression (F2,54=9.0, P<.001)
      and anxiety (F2,54=18.7, P<.001) significantly reduced across time. Higher levels
      of confidence were significantly associated with actions taken at 1 (P=.005) and
      6 weeks (P=.04), and higher levels of importance were significantly associated
      with actions taken at 1 (P=.009) and 6 weeks (P=.003). Higher levels of
      confidence were associated with lower levels of depression (P=.04) and anxiety
      (P=.01) at 6 weeks. CONCLUSIONS: Preliminary findings indicate a culturally
      tailored mental health transmedia intervention is a feasible approach that holds
      promise for engaging large numbers of symptomatic English-speaking Latina women
      to begin the process of seeking help, as well as decreasing symptoms of anxiety
      and depression.

PMID- 29051136
TI  - Using Google Glass in Nonsurgical Medical Settings: Systematic Review.
AB  - BACKGROUND: Wearable technologies provide users hands-free access to computer
      functions and are becoming increasingly popular on both the consumer market and
      in various industries. The medical industry has pioneered research and
      implementation of head-mounted wearable devices, such as Google Glass. Most of
      this research has focused on surgical interventions; however, other medical
      fields have begun to explore the potential of this technology to support both
      patients and clinicians. OBJECTIVE: Our aim was to systematically evaluate the
      feasibility, usability, and acceptability of using Google Glass in nonsurgical
      medical settings and to determine the benefits, limitations, and future
      directions of its application. METHODS: This review covers literature published
      between January 2013 and May 2017. Searches included PubMed MEDLINE, Embase,
      INSPEC (Ebsco), Cochrane Central Register of Controlled Trials (CENTRAL), IEEE
      Explore, Web of Science, Scopus, and Compendex. The search strategy sought all
      articles on Google Glass. Two reviewers independently screened titles and
      abstracts, assessed full-text articles, and extracted data from articles that met
      all predefined criteria. Any disagreements were resolved by discussion or
      consultation by the senior author. Included studies were original research
      articles that evaluated the feasibility, usability, or acceptability of Google
      Glass in nonsurgical medical settings. The preferred reporting results of
      systematic reviews and meta-analyses (PRISMA) guidelines were followed for
      reporting of results. RESULTS: Of the 852 records examined, 51 met all predefined
      criteria, including patient-centered (n=21) and clinician-centered studies
      (n=30). Patient-centered studies explored the utility of Google Glass in
      supporting patients with motor impairments (n=8), visual impairments (n=5),
      developmental and psychiatric disorders (n=2), weight management concerns (n=3),
      allergies (n=1), or other health concerns (n=2). Clinician-centered studies
      explored the utility of Google Glass in student training (n=9), disaster relief
      (n=4), diagnostics (n=2), nursing (n=1), autopsy and postmortem examination
      (n=1), wound care (n=1), behavioral sciences (n=1), and various medical
      subspecialties, including, cardiology (n=3), radiology (n=3), neurology (n=1),
      anesthesiology (n=1), pulmonology (n=1), toxicology (n=1), and dermatology (n=1).
      Most of the studies were conducted in the United States (40/51, 78%), did not
      report specific age information for participants (38/51, 75%), had sample size
      <30 participants (29/51, 57%), and were pilot or feasibility studies (31/51,
      61%). Most patient-centered studies (19/21, 90%) demonstrated feasibility with
      high satisfaction and acceptability among participants, despite a few technical
      challenges with the device. A number of clinician-centered studies (11/30, 37%)
      reported low to moderate satisfaction among participants, with the most promising
      results being in the area of student training. Studies varied in sample size,
      approach for implementation of Google Glass, and outcomes assessment.
      CONCLUSIONS: The use of Google Glass in nonsurgical medical settings varied. More
      promising results regarding the feasibility, usability, and acceptability of
      using Google Glass were seen in patient-centered studies and student training
      settings. Further research evaluating the efficacy and cost-effectiveness of
      Google Glass as an intervention to improve important clinical outcomes is
      warranted.

PMID- 29051137
TI  - Alzheimer's Disease in Social Media: Content Analysis of YouTube Videos.
AB  - BACKGROUND: Approximately 5.5 million Americans are living with Alzheimer's
      disease (AD) in 2017. YouTube is a popular platform for disseminating health
      information; however, little is known about messages specifically regarding AD
      that are being communicated through YouTube. OBJECTIVE: This study aims to
      examine video characteristics, content, speaker characteristics, and mobilizing
      information (cues to action) of YouTube videos focused on AD. METHODS: Videos
      uploaded to YouTube from 2013 to 2015 were searched with the term "Alzheimer's
      disease" on April 30th, 2016. Two coders viewed the videos and coded video
      characteristics (the date when a video was posted, Uniform Resource Locator,
      video length, audience engagement, format, author), content, speaker
      characteristics (sex, race, age), and mobilizing information. Descriptive
      statistics were used to examine video characteristics, content, audience
      engagement (number of views), speaker appearances in the video, and mobilizing
      information. Associations between variables were examined using Chi-square and
      Fisher's exact tests. RESULTS: Among the 271 videos retrieved, 25.5% (69/271)
      were posted by nonprofit organizations or universities. Informal presentations
      comprised 25.8% (70/271) of all videos. Although AD symptoms (83/271, 30.6%),
      causes of AD (80/271, 29.5%), and treatment (76/271, 28.0%) were commonly
      addressed, quality of life of people with AD (34/271, 12.5%) had more views than
      those more commonly-covered content areas. Most videos featured white speakers
      (168/187, 89.8%) who were adults aged 20 years to their early 60s (164/187,
      87.7%). Only 36.9% (100/271) of videos included mobilizing information. Videos
      about AD symptoms were significantly less likely to include mobilizing
      information compared to videos without AD symptoms (23/83, 27.7% vs 77/188, 41.0%
      respectively; P=.03). CONCLUSIONS: This study contributes new knowledge regarding
      AD messages delivered through YouTube. Findings of the current study highlight a
      potential gap between available information and viewers' interests. YouTube
      videos on AD could be beneficial if the messages delivered meet users' needs and
      provide mobilizing information for further resources. Study findings will be
      useful to government agencies, researchers, nonprofit organizations that promote
      information about AD, and those responsible for social media to provide useful
      and accurate health information for the public.

PMID- 29051138
TI  - Effectiveness of Two Web-Based Interventions for Chronic Cancer-Related Fatigue
      Compared to an Active Control Condition: Results of the "Fitter na kanker"
      Randomized Controlled Trial.
AB  - BACKGROUND: Approximately one third of all patients who have been successfully
      treated for cancer suffer from chronic cancer-related fatigue (CCRF). Effective
      and easily accessible interventions are needed for these patients. OBJECTIVE: The
      current paper reports on the results of a 3-armed randomized controlled trial
      investigating the clinical effectiveness of two different guided Web-based
      interventions for reducing CCRF compared to an active control condition. METHODS:
      Severely fatigued cancer survivors were recruited via online and offline
      channels, and self-registered on an open-access website. After eligibility
      checks, 167 participants were randomized via an embedded automated randomization
      function into: (1) physiotherapist-guided Ambulant Activity Feedback (AAF)
      therapy encompassing the use of an accelerometer (n=62); (2) psychologist-guided
      Web-based mindfulness-based cognitive therapy (eMBCT; n=55); or (3) an unguided
      active control condition receiving psycho-educational emails (n=50). All
      interventions lasted nine weeks. Fatigue severity was self-assessed using the
      Checklist Individual Strength - Fatigue Severity subscale (primary outcome) six
      times from baseline (T0b) to six months (T2). Mental health was self-assessed
      three times using the Hospital Anxiety and Depression Scale and Positive and
      Negative Affect Schedule (secondary outcome). Treatment dropout was investigated.
      RESULTS: Multiple group latent growth curve analysis, corrected for individual
      time between assessments, showed that fatigue severity decreased significantly
      more in the AAF and eMBCT groups compared to the psycho-educational group. The
      analyses were checked by a researcher who was blind to allocation. Clinically
      relevant changes in fatigue severity were observed in 66% (41/62) of patients in
      AAF, 49% (27/55) of patients in eMBCT, and 12% (6/50) of patients in psycho
      education. Dropout was 18% (11/62) in AAF, mainly due to technical problems and
      poor usability of the accelerometer, and 38% (21/55) in eMBCT, mainly due to the
      perceived high intensity of the program. CONCLUSIONS: Both the AAF and eMBCT
      interventions are effective for managing fatigue severity compared to receiving
      psycho-educational emails. TRIAL REGISTRATION: Trialregister.nl NTR3483;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3483 (Archived by
      WebCite at http://www.webcitation.org/6NWZqon3o).

PMID- 29051139
TI  - Mining the Stiffness-Sensitive Transcriptome in Human Vascular Smooth Muscle
      Cells Identifies Long Noncoding RNA Stiffness Regulators.
AB  - OBJECTIVE: Vascular extracellular matrix stiffening is a risk factor for aortic
      and coronary artery disease. How matrix stiffening regulates the transcriptome
      profile of human aortic and coronary vascular smooth muscle cells (VSMCs) is not
      well understood. Furthermore, the role of long noncoding RNAs (lncRNAs) in the
      cellular response to stiffening has never been explored. This study characterizes
      the stiffness-sensitive (SS) transcriptome of human aortic and coronary VSMCs and
      identifies potential key lncRNA regulators of stiffness-dependent VSMC functions.
      APPROACH AND RESULTS: Aortic and coronary VSMCs were cultured on hydrogel
      substrates mimicking physiological and pathological extracellular matrix
      stiffness. Total RNAseq was performed to compare the SS transcriptome profiles of
      aortic and coronary VSMCs. We identified 3098 genes (2842 protein coding and 157
      lncRNA) that were stiffness sensitive in both aortic and coronary VSMCs (false
      discovery rate <1%). Hierarchical clustering revealed that aortic and coronary
      VSMCs grouped by stiffness rather than cell origin. Conservation analyses also
      revealed that SS genes were more conserved than stiffness-insensitive genes.
      These VSMC SS genes were less tissue-type specific and expressed in more tissues
      than stiffness-insensitive genes. Using unbiased systems analyses, we identified
      MALAT1 as an SS lncRNA that regulates stiffness-dependent VSMC proliferation and
      migration in vitro and in vivo. CONCLUSIONS: This study provides the
      transcriptomic landscape of human aortic and coronary VSMCs in response to
      extracellular matrix stiffness and identifies novel SS human lncRNAs. Our data
      suggest that the SS transcriptome is evolutionarily important to VSMCs function
      and that SS lncRNAs can act as regulators of stiffness-dependent phenotypes.

PMID- 29051140
TI  - FGD5 Regulates VEGF Receptor-2 Coupling to PI3 Kinase and Receptor Recycling.
AB  - OBJECTIVE: VEGF (vascular endothelial growth factor-A) signaling to the
      endothelial cell (EC) through VEGFR2 (VEGF receptor-2) is the principal cue
      driving new blood vessel formation. FGD5 (faciogenital dysplasia-5)-a Rho-family
      guanine nucleotide exchange factor-is selectively expressed in EC. Deficiency of
      FGD5 is embryonically lethal in mice and perturbs angiogenesis and VEGF signal
      transduction. However, the mechanism of FGD5 regulation of VEGF signaling is
      poorly understood. APPROACH AND RESULTS: Angiogenic sprouting and EC cytoskeletal
      remodeling were evaluated in a 3-dimensional in vitro model. We examined the
      subcellular localization of FGD5 and VEGFR2 in EC by immunofluorescent staining
      and studied the association by immunoprecipitation. FGD5 deficiency reduced the
      number of angiogenic sprouts and tip cell filopodia by ~80% and ~70%,
      respectively. These defects were accompanied by downregulation of the expression
      of tip cell-specific markers. FGD5 inactivation led to a decrease in EC migration
      and early protrusion (lamellipodia) formation. In resting and VEGF-stimulated EC,
      FGD5 forms a complex with VEGFR2 and was enriched at the leading edge of the cell
      and among endosomes. FGD5 loss reduced mTORC2 (mammalian target of rapamycin
      complex-2)/Akt-dependent cortactin activation downstream of VEGFR2 but did not
      alter VEGFR2 plasma membrane expression, Y1175 phosphorylation, or endocytosis.
      However, FGD5 loss decreased endosomal VEGFR2 coupling to phosphoinositide-3
      kinase and diverted VEGFR2 to lysosomal degradation. CONCLUSIONS: FGD5 regulates
      VEGFR2 retention in recycling endosomes and coupling to PI3 (phosphoinositide-3)
      kinase/mTORC2-dependent cytoskeletal remodeling.

PMID- 29051141
TI  - Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute
      Myocardial Infarction.
AB  - OBJECTIVE: Coronary artery ectasia (CAE) is an infrequently observed vascular
      phenotype characterized by abnormal vessel dilatation and disturbed coronary
      flow, which potentially promote thrombogenicity and inflammatory reactions.
      However, whether or not CAE influences cardiovascular outcomes remains unknown.
      APPROACH AND RESULTS: We investigated major adverse cardiac events (MACE; defined
      as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with
      acute MI. The occurrence of MACE was compared in patients with and without CAE.
      CAE was identified in 3.0% of study subjects. During the 49-month observation
      period, CAE was associated with 3.25-, 2.71-, and 4.92-fold greater likelihoods
      of experiencing MACE (95% confidence interval [CI], 1.88-5.66; P<0.001), cardiac
      death (95% CI, 1.37-5.37; P=0.004), and nonfatal MI (95% CI, 2.20-11.0; P<0.001),
      respectively. These cardiac risks of CAE were consistently observed in a
      multivariate Cox proportional hazards model (MACE: hazard ratio, 4.94; 95% CI,
      2.36-10.4; P<0.001) and in a propensity score-matched cohort (MACE: hazard ratio,
      8.98; 95% CI, 1.14-71.0; P=0.03). Despite having a higher risk of CAE-related
      cardiac events, patients with CAE receiving anticoagulation therapy who achieved
      an optimal percent time in target therapeutic range, defined as >=60%, did not
      experience the occurrence of MACE (P=0.03 versus patients with percent time in
      target therapeutic range <60% or without anticoagulation therapy). CONCLUSIONS:
      The presence of CAE predicted future cardiac events in patients with acute MI.
      Our findings suggest that acute MI patients with CAE are a high-risk subset who
      might benefit from a pharmacological approach to controlling the coagulation
      cascade.

PMID- 29051142
TI  - APOL1 and Proteinuria in the AASK: Unraveling the Pathobiology of APOL1.

PMID- 29051143
TI  - Health Care Costs Associated with AKI.
AB  - BACKGROUND AND OBJECTIVES: An understanding of the health care resource use
      associated with AKI is needed to frame the investment and cost-effectiveness of
      strategies to prevent AKI and promote kidney recovery. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We assembled population-based cohort of adults
      hospitalized in Alberta between November of 2002 and March of 2009 without ESRD
      or an eGFR<15 ml/min per 1.73 m2. Outpatient serum creatinine measurements 6
      months preceding admission defined baseline kidney function, and serum creatinine
      during the first 14 days of hospitalization defined Acute Kidney Injury Network
      stage; kidney recovery defined as serum creatinine within 25% of baseline and
      independence from dialysis was assessed at 90 days after AKI. Health care
      utilization and costs (in 2015 Canadian dollars) were determined from inpatient,
      outpatient, and physician claims datasets during the index hospitalization,
      recovery period (90 days post-AKI assessment), and 3-12 months post-AKI. A fully
      adjusted generalized linear model regression analysis was used to estimate costs
      associated with AKI. RESULTS: Of 239,906 hospitalized subjects, 25,495 (10.6%),
      4598 (1.9%), 2493 (1.0%), and 670 (0.3%) had Acute Kidney Injury Network stages
      1, 2, 3 without dialysis, and 3 with dialysis, respectively. Greater severity of
      AKI was associated with incremental increases in length of stay (+2.8; 95%
      confidence interval, 1.4 to 4.3 to +7.4; 95% confidence interval, 7.2 to 7.5
      days) and costs (+$3779; 95% confidence interval, $3555 to $4004 to +$18,291; 95%
      confidence interval, $15,573 to $21,009 Canadian dollars) from admission to
      recovery assessment (3 months). At months 3-12 postadmission, compared with
      subjects without AKI, AKI with kidney recovery and AKI without kidney recovery
      were associated with incremental costs of +$2912-$3231 and +$6035-$8563 Canadian
      dollars, respectively. The estimated incremental cost of AKI in Canada is
      estimated to be over $200 million Canadian dollars per year. CONCLUSIONS:
      Severity of AKI, need for dialysis, and lack of kidney recovery are associated
      with significant health care costs in hospitalized patients and persist a year
      after admission. Strategies to identify, prevent, and facilitate kidney recovery
      are needed.

PMID- 29051145
TI  - A Discrete Choice Study of Patient Preferences for Dialysis Modalities.
AB  - BACKGROUND AND OBJECTIVES: Improved knowledge about factors that influence
      patient choices when considering dialysis modality could facilitate health care
      interventions to increase rates of home dialysis. We aimed to quantify the
      attributes of dialysis care and the tradeoffs that patients consider when making
      decisions about dialysis modalities. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We conducted a prospective, discrete choice experiment survey with
      random parameter logit analysis to quantify preferences and tradeoffs for
      attributes of dialysis treatment in 143 adult patients with CKD expected to
      require RRT within 12 months (predialysis). The attributes included schedule
      flexibility, patient out of pocket costs, subsidized transport services, level of
      nursing support, life expectancy, dialysis training time, wellbeing on dialysis,
      and dialysis schedule (frequency and duration). We reported outcomes using beta
      coefficients with corresponding odds ratios and 95% confidence intervals for
      choosing home-based dialysis (peritoneal dialysis or hemodialysis) compared with
      facility hemodialysis. RESULTS: Home-based therapies were significantly preferred
      with the following attributes: longer survival (odds ratio per year, 1.63; 95%
      confidence interval, 1.25 to 2.12), increased treatment flexibility (odds ratio,
      9.22; 95% confidence interval, 2.71 to 31.3), improved wellbeing (odds ratio,
      210; 95% confidence interval, 15 to 2489), and more nursing support (odds ratio,
      87.3; 95% confidence interval, 3.8 to 2014). Respondents were willing to accept
      additional out of pocket costs of approximately New Zealand $400 (United States
      $271) per month (95% confidence interval, New Zealand $333 to $465) to receive
      increased nursing support. Patients were willing to accept out of pocket costs of
      New Zealand $223 (United States $151) per month (95% confidence interval, New
      Zealand $195 to $251) for more treatment flexibility. CONCLUSIONS: Patients
      preferred home dialysis over facility-based care when increased nursing support
      was available and when longer survival, wellbeing, and flexibility were expected.
      Sociodemographics, such as age, ethnicity, and income, influenced patient choice.

PMID- 29051144
TI  - Sociodemographic, Psychologic Health, and Lifestyle Outcomes in Young Adults on
      Renal Replacement Therapy.
AB  - BACKGROUND AND OBJECTIVES: Young adults receiving RRT face additional challenges
      in life. The effect of established kidney failure on young adulthood is
      uncertain. We aimed to establish the psychosocial and lifestyle status of young
      adults receiving RRT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study
      was a systematic review and meta-analysis of 16-30-year olds receiving RRT
      compared with the general population. We selected randomized, controlled trials;
      cohort studies; or cross-sectional studies without language restriction and
      extracted proportions of sociodemographic and lifestyle outcomes or validated
      psychologic health tests producing quality of life, wellbeing, and self-esteem
      scores. We undertook random effects meta-analysis. RESULTS: There were 60 studies
      with a total of 15,575 participants. Studies were largely single-center cross
      sectional studies of those transplanted in childhood. Compared with healthy
      peers, young adults on RRT had lower quality of life, which was worse for
      patients on dialysis (seven studies: standardized mean difference, -1.01; 95%
      confidence interval [95% CI], -1.32 to -0.70) compared with patients with
      transplants (nine studies: standardized mean difference, -0.42; 95% CI, -0.64 to 
      0.20). They were more likely to be unemployed (seven studies: relative risk,
      1.89; 95% CI, 1.47 to 2.44) and live in the family home (two studies: relative
      risk, 1.84; 95% CI, 1.40 to 2.43). They were less likely to be married or have a
      partner (four studies: relative risk, 0.71; 95% CI, 0.53 to 0.95). Higher
      education (three studies: relative risk, 1.05; 95% CI, 0.73 to 1.51), alcohol
      abstinence (three studies: relative risk, 1.96; 95% CI, 0.84 to 4.67), and
      smoking status (two studies: relative risk, 0.72; 95% CI, 0.36 to 1.44) did not
      differ. Results were limited by high heterogeneity and a small evidence base,
      biased toward surviving patients. CONCLUSIONS: Established kidney failure is
      associated with lower quality of life in young people and limited employment,
      independence, and relationships compared with healthy peers. PODCAST: This
      article contains a podcast at https://www.asn
      online.org/media/podcast/CJASN/2017_10_19_CJASNPodcast_17_12_.mp3.

PMID- 29051148
TI  - Limits on prescribing will harm rural and poorer patients, doctors warn.

PMID- 29051146
TI  - APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks
      with Hypertension-Attributed CKD.
AB  - BACKGROUND AND OBJECTIVES: The natural history of kidney disease among blacks who
      carry the APOL1 high-risk variants varies, with only a subgroup progressing to
      ESRD. We aimed to determine whether the APOL1 risk variants are associated with
      incident proteinuria in the context of hypertension-attributed CKD, and whether
      subsequent kidney function decline after the onset of proteinuria differs by
      APOL1 risk status. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using Cox
      models, we studied the association between APOL1 risk status and incident
      proteinuria (defined as a doubling of urine protein-to-creatinine ratio to a
      level >=0.22 g/g creatinine) among African-American Study of Kidney Disease and
      Hypertension (AASK) trial participants with APOL1 genotyping and without
      proteinuria at baseline. RESULTS: Of the 480 participants in our study, 82 (17%)
      had the high-risk genotypes (2 alleles), and 254 (53%) developed proteinuria over
      a median follow-up of 6.8 years. At baseline, mean eGFR was lower in the APOL1
      high-risk group compared with the low-risk group (0 or 1 allele; 49.6 versus 53.2
      ml/min per 1.73 m2, respectively; P=0.02), but median proteinuria was similar
      (0.04 g/g creatinine for both groups; P=0.43). Individuals with the high-risk
      genotypes were 1.72-fold more likely to develop incident proteinuria compared
      with those with the low-risk genotypes (95% confidence interval, 1.27 to 2.32),
      independent of age, sex, ancestry, baseline eGFR, baseline systolic BP, and
      randomized treatment groups. Although eGFR declined faster after the onset of
      proteinuria, this rate did not differ significantly by APOL1 risk status.
      CONCLUSIONS: Among blacks with established moderate CKD, the APOL1 high-risk
      variants are associated with greater risk of incident proteinuria. After
      proteinuria onset, kidney function declines more rapidly but does not differ by
      APOL1 risk status. This suggests that factors that lead to proteinuria, beyond
      APOL1, may additionally drive CKD progression.

PMID- 29051147
TI  - Organic Anion-Transporting Polypeptide (OATP)-Mediated Drug-Drug Interaction
      Study between Rosuvastatin and Cyclosporine A in Chimeric Mice with Humanized
      Liver.
AB  - The influence of transporters on the pharmacokinetics of drugs is being
      increasingly recognized, and DDIs via transporters may be a risk factor for
      adverse events. Cyclosporine A, a strong OATP inhibitor, has been reported to
      increase the systemic exposure of rosuvastatin, an OATP substrate, by 7.1-fold in
      clinical studies. PXB mice are chimeric mice with humanized livers that are
      highly repopulated with human hepatocytes and have been widely used for drug
      discovery in drug metabolism and pharmacokinetics studies. In the present study,
      we examined in vivo and in vitro DDIs between rosuvastatin and cyclosporine A in
      PXB mice and fresh human hepatocytes (PXB cells) obtained from PXB mice. We
      initially investigated the active transport of rosuvastatin into PXB cells, and
      found concentration-dependent uptake with a Michaelis-Menten constant value of
      4.0 MUmol/l and a Vmax value of 4.63 pmol/min per 106 cells. Cyclosporine A
      inhibited the uptake of rosuvastatin with an IC50 value of 0.21 MUmol/l. We then
      examined in vivo DDIs, and the exposure of orally administered rosuvastatin
      increased by 3.3-fold and 11-fold in PXB mice pretreated with 10 and 50 mg/kg
      cyclosporine A, whereas it increased by 2.5-fold and 6.2-fold when rosuvastatin
      was administered intravenously, in studies that were conducted for considering
      gastrointestinal DDIs. The liver-to-blood concentration ratio of rosuvastatin was
      dose-dependently decreased by pretreatment with cyclosporine A in PXB mice and
      SCID mice. Observed DDIs in vivo were considered to be reasonable based on the
      estimated concentrations of cyclosporine A at the inlet to the liver and in the
      liver tissues of both mice. In conclusion, our results indicate that PXB mice
      might be a useful tool for predicting human OATP-mediated DDIs in drug discovery,
      and its limitation due to the differences of gastrointestinal condition from
      human should also be considered.

PMID- 29051149
TI  - Resolution of a human mast cell development conundrum.

PMID- 29051150
TI  - Lymphoma "benchmark" or "bench-smudge"?

PMID- 29051151
TI  - Understanding lymphoma molecular complexity.

PMID- 29051152
TI  - Time for ALL adults to catch up with the children.

PMID- 29051153
TI  - MPO-negative inclusions and Auer rod-like structures in a case of acute myeloid
      leukemia with t(8;21).

PMID- 29051155
TI  - Genomic analysis of adult Burkitt lymphoma.

PMID- 29051154
TI  - Incidental Langerhans cell histiocytosis of the colon with BRAF p.V600E mutation.

PMID- 29051156
TI  - How inappropriate prescribing prompted the opioid addiction ravaging small town
      America.

PMID- 29051158
TI  - Family veto in organ donation in Canada: framing within English-language
      newspaper articles.
AB  - BACKGROUND: Because organ transplantation relies on public support for donation,
      an analysis of public discourse around organ donation is essential. We
      investigated the portrayal of family veto - when a family overrides the deceased
      person's prior legally executed wishes to donate - in Canadian news media.
      METHODS: Using the Canadian Newsstream database, we identified articles published
      in English-language newspapers addressing family veto between 2000 and 2016.
      Guided by the theoretical perspectives of framing of media effects, we conducted
      a systematic content analysis of the articles to examine how the Canadian media
      framed family veto. An initial in-depth analysis of the data set in which themes
      and patterns were captured and recorded identified coding categories, including
      primary framing of family veto, prevalence, reasons, ethical or legal concerns
      and overall tone of the article. Two coders analyzed the data set to ensure
      intercoder reliability. RESULTS: A total of 133 relevant articles were
      identified. Family veto was framed predominantly as something that should not be
      allowed (81 articles [60.9%]) and as a reality that is little understood outside
      the transplantation community (45 [33.8%]). One-quarter of the articles (32
      [24.1%]) highlighted ethical principles of autonomy and justice associated with
      family veto. Family veto was represented as a stumbling block in the present
      organ donation system, with most publications (107 [80.4%]) calling for change.
      There were differing interpretations of organ donation legislation, with 82
      articles (61.6%) erroneously stating or suggesting that existing legislation
      permits family veto. INTERPRETATION: Family veto in organ donation was portrayed
      predominantly negatively. Many publications reflected a misunderstanding of the
      law concerning this issue. Although the framing of family veto highlighted
      important ethical and legal concerns as well as practice and policy
      considerations, research is needed to enhance the understanding of family veto in
      organ donation.

PMID- 29051159
TI  - Metformin Use May Moderate the Effect of DPP-4 Inhibitors on Cardiovascular
      Outcomes.
AB  - OBJECTIVE: To explore prevalent metformin use as a potential moderator of the
      cardiovascular effects of dipeptidyl peptidase 4 inhibitors (DPP-4i). RESEARCH
      DESIGN AND METHODS: We performed a meta-analysis of the three major
      cardiovascular outcomes trials examining DPP-4i. We used meta-regression to
      examine how the cardiovascular effects of DPP-4i differ between prevalent
      metformin users and baseline nonusers. RESULTS: While prevalent metformin users
      experienced a trend toward improved cardiovascular outcomes with DPP-4i (summary
      hazard ratio [HR] 0.92 [95% CI 0.84, 1.01]), baseline metformin nonusers showed a
      trend toward harm (HR 1.10 [95% CI 0.97, 1.26]). The difference in overall DPP-4i
      effect between metformin user and nonuser subgroups was statistically significant
      (P = 0.036). CONCLUSIONS: Baseline metformin status may have a moderating effect
      on cardiovascular outcomes with DPP-4i use. This hypothesis-generating analysis
      suggests there is residual uncertainty as to how DPP-4i affect cardiovascular
      outcomes, depending on concurrently prescribed medications.

PMID- 29051162
TI  - Sports medicine highlights from other journals.

PMID- 29051160
TI  - The Prognostic Significance of Diabetes and Microvascular Complications in
      Patients With Heart Failure With Preserved Ejection Fraction.
AB  - OBJECTIVE: This study examined the prognostic significance of diabetes and
      microvascular complications in patients with heart failure with preserved
      ejection fraction (HFpEF). RESEARCH DESIGN AND METHODS: This analysis included
      3,385 patients (mean age 69 +/- 9.6 years; 49% male; 89% white) with HFpEF from
      the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone
      Antagonist Trial (TOPCAT). Diabetes and microvascular complications were
      ascertained by self-reported history and medical record review. Microvascular
      complications included neuropathy, nephropathy, and retinopathy. Outcomes
      included hospitalization, hospitalization for heart failure, death, and
      cardiovascular death. Cox regression was used to examine the risk of each outcome
      associated with diabetes and microvascular complications. RESULTS: Of the 1,109
      subjects (32%) with diabetes, 352 (32%) had at least one microvascular
      complication. Patients with diabetes and microvascular complications had an
      increased risk for hospitalization (no diabetes: referent; diabetes + no
      microvascular complication: hazard ratio [HR] 1.18, 95% CI 1.01, 1.37; diabetes +
      microvascular complications: HR 1.54, 95% CI 1.25, 1.89; P-trend <0.001),
      hospitalization for heart failure (no diabetes: referent; diabetes + no
      microvascular complication: HR 1.51, 95% CI 1.14, 1.99; diabetes + microvascular
      complications: HR 1.97, 95% CI 1.38, 2.80; P-trend <0.001), death (no diabetes:
      referent; diabetes + no microvascular complication: HR 1.35, 95% CI 1.04, 1.75;
      diabetes + microvascular complications: HR 1.73, 95% CI 1.22, 2.45; P-trend =
      0.0017), and cardiovascular death (no diabetes: referent; diabetes + no
      microvascular complication: HR 1.34, 95% CI 0.96, 1.86; diabetes + microvascular
      complications: HR 1.70, 95% CI 1.09, 2.65; P-trend = 0.018). When the analysis
      was limited to participants who reported prior hospitalization for heart failure
      (n = 2,449), a higher risk of rehospitalization for heart failure was observed
      across diabetes categories (no diabetes: referent; diabetes + no microvascular
      complication: HR 1.40, 95% CI 1.01, 1.96; diabetes + microvascular complications:
      HR 1.78, 95% CI 1.18, 2.70; P-trend = 0.0036). CONCLUSIONS: Diabetes is
      associated with adverse cardiovascular outcomes in HFpEF, and the inherent risk
      of adverse outcomes in HFpEF patients with diabetes varies by the presence of
      microvascular complications.

PMID- 29051161
TI  - Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen
      Deprivation, Improving Recognition by AR-Specific T Cells.
AB  - Androgen deprivation is the primary therapy for recurrent prostate cancer, and
      agents targeting the androgen receptor (AR) pathway continue to be developed.
      Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well
      as direct antitumor effects, AR-targeted therapies have been combined with other
      anticancer therapies, including immunotherapies. Here, we sought to study whether
      an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may
      result in enhanced AR-specific T-cell immune recognition, and whether this might
      be strategically combined with an antitumor vaccine targeting the AR. Androgen
      deprivation increased AR expression in human and murine prostate tumor cells in
      vitro and in vivo The increased expression persisted over time. Increased AR
      expression was associated with recognition and cytolytic activity by AR-specific
      T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine
      encoding the ligand-binding domain of the AR, led to improved antitumor responses
      as measured by tumor volumes and delays in the emergence of castrate-resistant
      prostate tumors in two murine prostate cancer models (Myc-CaP and prostate
      specific PTEN-deficient mice). Together, these data suggest that ADT combined
      with AR-directed immunotherapy targets a major mechanism of resistance,
      overexpression of the AR. This combination may be more effective than ADT
      combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074
      85. (c)2017 AACR.

PMID- 29051163
TI  - Do sports medicine clinicians have credible alternatives to knee arthroscopy for
      the degenerative knee?

PMID- 29051165
TI  - University of Birmingham: an innovative Masters of Exercise and Sports Medicine
      in partnership with the Football Association (Continuing Professional Development
      series).

PMID- 29051164
TI  - Infographic: physical activity for pregnant women.

PMID- 29051166
TI  - Epidemiology of imaging-detected tendon abnormalities in athletes participating
      in the Rio de Janeiro 2016 Summer Olympics.
AB  - BACKGROUND: Tendon abnormalities are prevalent among both elite and non-elite
      athletes. Cross-sectional imaging modalities are used to confirm and evaluate the
      severity of such lesions. AIM: To describe the demographics, prevalence,
      anatomical location and characteristics of tendon abnormalities in athletes who
      participated in the Rio de Janeiro 2016 Summer Olympic Games. METHODS: We
      recorded all sports injuries reported by the National Olympic Committee (NOC)
      medical teams and the Organizing Committee medical staff during the Rio 2016
      Summer Olympics. Diagnostic imaging was performed through the official IOC clinic
      within the Olympic Village, using digital ultrasound machines and 3T and 1.5T MR
      scanners. Image interpretation was performed centrally by board-certified
      musculoskeletal radiologists with expertise in sports injuries. RESULTS: In
      total, 11 274 athletes (5089 women (45%), 6185 men (55%)) from 207 NOCs were
      included. NOC and Rio de Janeiro 2016 medical staff reported 1101 injuries.
      Central review of radiological images revealed 156 tendon abnormalities in 109
      athletes (51.2% male, mean age: 26.8, range 18-39). The supraspinatus tendon was
      the most commonly involved tendon (31 cases, 19.9%), followed by the Achilles
      tendon (20 cases, 12.8%) and patellar and infraspinatus tendons (12 cases, 7.7%).
      Tendon abnormalities were most commonly seen in track and field athletes (54
      abnormalities, 34.6%). CONCLUSION: 156 tendon abnormalities were reported, most
      commonly in track and field athletes, and involving mainly the shoulder tendons,
      as well as Achilles and patellar tendons.

PMID- 29051167
TI  - Hamstring muscle injuries in elite football: translating research into practice.

PMID- 29051168
TI  - Pain and fatigue in sport: are they so different?

PMID- 29051169
TI  - Epidemiology of injuries in juniors participating in top-level karate
      competition: a prospective cohort study.
AB  - BACKGROUND: Karate is a popular combat semi-contact sport among juniors, but
      there are only few studies available on the epidemiology of injuries in karate
      junior athletes. AIM: The aims of this study were to determine the incidence and
      pattern of injuries in top-level karate competition for athletes aged 16 to 20
      years, and to compare injury rates between age groups (ie, under 18-year-old
      [U18] and under 21-year-old [U21]) and genders, following the introduction of new
      weight categories. METHODS: A prospective injury surveillance was undertaken at
      four consecutive World Karate Championships (2009 to 2015), following the same
      protocols used in previous investigations. RESULTS: During the four
      championships, a total of 257 injuries were recorded, with an incidence of
      41.4/1,000 athlete exposures (AEs, 95% CI 36.4 to 46.3). The injury rate was
      significantly lower for females with a rate ratio 0.63 (95% CI 0.48 to 0.82).
      Most of the injuries were minor ones: contusions (n=100), followed by abrasions
      (n=63) and epistaxis (n=62). Only 10% of the injuries were time-loss injuries
      (injury incidence rates 4.2/1,000 AEs; 95% CI 2.7 to 6.1). Face injuries
      represented 69.6% of the injuries, most of them were minor ones (light abrasions
      24.5%, epistaxis 24.1%, contusion 16.7%). Change of rules (raising the number of
      weight categories from three to five) reduced injury incidence in the U21
      category. CONCLUSIONS: The total injury rate in junior competitions is lower
      compared with elite adult athletes and higher compared with younger elite
      athletes. Time-loss injuries are rare. The implementation of the new competition
      categories in U21 karate has been associated with a significant reduction in
      injury rate.

PMID- 29051170
TI  - Physical activity calendar.

PMID- 29051171
TI  - I know what the imaging guidelines say, but....

PMID- 29051172
TI  - Modelling the process of falling behind and its psychophysiological consequences.
AB  - INTRODUCTION: A preceding article investigated the psychophysiological responses
      to falling behind a performance matched opponent. The following temporally linked
      cause-effect relationships were hypothesised: falling behind precedes
      deterioration in valence, deterioration in valence precedes development of an
      action crisis, experience of an action crisis precedes
      psychoneuroendocrinological distress response and non-adaptive distress response
      reduces conduciveness to high performance, thereby preceding performance
      decrement. METHODS: In this article, we applied structural equation modelling to
      test the extent to which the observed data fit the hypothesised cause-effect
      relationships. A five-step procedure was applied to model the interrelationships
      between the major study variables in the hypothesised temporal order. RESULTS:
      Significant linear relationships were found between all hypothesised predictor
      and outcome variable pairs (p<0.024). The dynamic change in valence was a
      significant mediator (p=0.011) as it explained 35% of the relationship between
      falling behind and action crisis. All hypothesised cause-effect relationships
      continued to be significant after controlling for performance, descriptor,
      training and perceived strain variables. The observed data fitted the
      hypothesised structural model well with excellent model fit indices throughout.
      CONCLUSION: We applied, tested and confirmed the hypothesised debilitative
      psychophysiological processes that unfold in response to falling behind a
      performance matched opponent. The main findings were: deterioration in valence
      mediated the relationship between falling behind and action crisis, the mindset
      shift associated with an action crisis predicted increased blood cortisol
      concentrations and non-adaptive blood cortisol concentrations predicted
      performance decrement. The findings point towards the crucial role of affective
      and cognitive modifiers in centrally regulated and goal-directed exercise
      behaviour.

PMID- 29051173
TI  - Don't demonise prescription opioids.

PMID- 29051174
TI  - Overprescribing is major contributor to opioid crisis.

PMID- 29051175
TI  - Associations between residual depressive symptoms, cognition, and functioning in
      patients with euthymic bipolar disorder: results from the FACE-BD cohort.
AB  - BackgroundThe relationship between residual depressive symptoms, cognition and
      functioning in patients with euthymic bipolar disorder is a subject of
      debate.AimsTo assess whether cognition mediates the association between residual
      depressive symptoms and functioning in patients with bipolar disorder who were
      euthymic.MethodWe included 241 adults with euthymic bipolar disorder in a
      multicentre cross-sectional study. We used a battery of tests to assess six
      cognition domains. A path analysis was then used to perform a mediation analysis
      of the relationship between residual depressive symptoms, cognitive components
      and functioning.ResultsOnly verbal and working memory were significantly
      associated with better functioning. Residual depressive symptoms were associated
      with poorer functioning. No significant relationship was found between residual
      depressive symptoms and any cognitive component.ConclusionsCognition and residual
      depressive symptoms appear to be two independent sources of variation in the
      functioning of people with euthymic bipolar disorder.

PMID- 29051176
TI  - Impact of co-located welfare advice in healthcare settings: prospective quasi
      experimental controlled study.
AB  - BackgroundEvaluations of primary healthcare co-located welfare advice services
      have been methodologically limited.AimsTo examine the impact and cost
      consequences of co-located benefits and debt advice on mental health and service
      use.MethodProspective, controlled quasi-experimental study in eight intervention
      and nine comparator sites across North Thames. Changes in the proportion meeting
      criteria for common mental disorder (CMD, 12-item General Health Questionnaire);
      well-being scores (Shortened Warwick and Edinburgh Mental Well-being Scale), 3
      month GP consultation rate and financial strain were measured alongside funding
      costs and financial gains.ResultsRelative to controls, CMD reduced among women
      (ratio of odds ratios (rOR) = 0.37, 95% CI 0.20-0.70) and Black advice recipients
      (rOR = 0.09, 95% CI 0.03-0.28). Individuals whose advice resulted in positive
      outcomes demonstrated improved well-being scores (beta coefficient 1.29, 95% CI
      0.25-2.32). Reductions in financial strain (rOR = 0.42, 95% CI 0.23-0.77) but no
      changes in 3-month consultation rate were found. Per capita, advice recipients
      received L15 per L1 of funder investment.ConclusionsCo-located welfare advice
      improves short-term mental health and well-being, reduces financial strain and
      generates considerable financial returns.

PMID- 29051177
TI  - High intelligence and the risk of ADHD and other psychopathology.
AB  - BackgroundHigh intelligence may be associated with positive (adaptive, desired)
      outcomes, but may also come with disadvantages.AimsTo contribute empirically to
      the debate concerning whether a trade-off in IQ scores exists in relation to
      attention-deficit hyperactivity disorder (ADHD) and related problems, suggesting
      that high intelligence - like low intelligence - increases the risk of
      ADHD.MethodCurves of the relation between IQ score and ADHD problems were fitted
      to questionnaire data (parent, teacher, self-report} in a population-based study
      of 2221 children and adolescents aged 10-12 years. Externalising and
      internalising problems were included for comparison purposes.ResultsHigher IQ
      score was most strongly related to fewer attention problems, with more rater
      discrepancy in the high v. average IQ range. Attention problems - but only
      minimally hyperactivity/impulsivity problems - predicted functional impairment at
      school, also in the higher IQ range.ConclusionsAttention problems in highly
      intelligent children are exceptional and affect school performance; they are
      therefore a reason for clinical concern.

PMID- 29051178
TI  - TLR4-Mediated Inflammation Promotes KSHV-Induced Cellular Transformation and
      Tumorigenesis by Activating the STAT3 Pathway.
AB  - Toll-like receptors (TLR) are conserved immune sensors mediating antimicrobial
      and antitumoral responses, but recent evidence implicates them in promoting
      carcinogenesis in certain cancers. Kaposi sarcoma is caused by infection of
      Kaposi sarcoma-associated herpesvirus (KSHV) and is characterized by uncontrolled
      neoangiogenesis and inflammation. Here, we show that TLR4 is upregulated in KSHV
      infected spindle tumor cells in human Kaposi sarcoma lesions. In a model of KSHV
      induced cellular transformation, KSHV upregulated expression of TLR4, its adaptor
      MyD88, and coreceptors CD14 and MD2. KSHV induction of TLR4 was mediated by
      multiple viral miRNAs. Importantly, the TLR4 pathway was activated constitutively
      in KSHV-transformed cells, resulting in chronic induction of IL6, IL1beta, and
      IL18. Accordingly, IL6 mediated constitutive activation of the STAT3 pathway, an
      essential event for uncontrolled cellular proliferation and transformation. TLR4
      stimulation with lipopolysaccharides or live bacteria enhanced tumorigenesis
      while TLR4 antagonist CLI095 inhibited it. These results highlight an essential
      role of the TLR4 pathway and chronic inflammation in KSHV-induced tumorigenesis,
      which helps explain why HIV-infected patients, who frequently suffer from
      opportunistic bacterial infections and metabolic complications, frequently
      develop Kaposi sarcoma. Cancer Res; 77(24); 7094-108. (c)2017 AACR.

PMID- 29051179
TI  - Analysis of ITGB2 rare germ line variants in chronic lymphocytic leukemia.

PMID- 29051180
TI  - Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new
      hope to AML.
AB  - In 2017, 4 drugs received US Food and Drug Administration marketing approval for
      acute myeloid leukemia (AML) treatment: targeted therapies for mutant FLT3 and
      IDH2, a liposomal cytarabine-daunorubicin formulation for therapy-related AML and
      AML with myelodysplasia-related changes, and resurgence of an antibody-drug
      conjugate designed to target CD33. Promising results also emerged for the BCL-2
      inhibitor venetoclax combined with low-intensity therapy in older patients unfit
      for intensive chemotherapy. This quintet of new drugs is likely to reshape the
      therapeutic landscape of AML.

PMID- 29051181
TI  - Disorders of erythrocyte hydration.
AB  - The erythrocyte contains a network of pathways that regulate salt and water
      content in the face of extracellular and intracellular osmotic perturbations.
      This allows the erythrocyte to maintain a narrow range of cell hemoglobin
      concentration, a process critical for normal red blood cell function and
      survival. Primary disorders that perturb volume homeostasis jeopardize the
      erythrocyte and may lead to its premature destruction. These disorders are marked
      by clinical, laboratory, and physiologic heterogeneity. Recent studies have
      revealed that these disorders are also marked by genetic heterogeneity. They have
      implicated roles for several proteins, PIEZO1, a mammalian mechanosensory
      protein; GLUT1, the glucose transporter; SLC4A1, the anion transporter; RhAG, the
      Rh-associated glycoprotein; KCNN4, the Gardos channel; and ABCB6, an adenosine
      triphosphate-binding cassette family member, in the maintenance of erythrocyte
      volume homeostasis. Secondary disorders of erythrocyte hydration include sickle
      cell disease, thalassemia, hemoglobin CC, and hereditary spherocytosis, where
      cellular dehydration may be a significant contributor to disease pathology and
      clinical complications. Understanding the pathways regulating erythrocyte water
      and solute content may reveal innovative strategies to maintain normal volume in
      disorders associated with primary or secondary cellular dehydration. These
      mechanisms will serve as a paradigm for other cells and may reveal new
      therapeutic targets for disease prevention and treatment beyond the erythrocyte.

PMID- 29051182
TI  - Oncogenetic mutations combined with MRD improve outcome prediction in pediatric T
      cell acute lymphoblastic leukemia.
AB  - Risk stratification in childhood T-cell acute lymphoblastic leukemia (T-ALL) is
      mainly based on minimal residual disease (MRD) quantification. Whether
      oncogenetic mutation profiles can improve the discrimination of MRD-defined risk
      categories was unknown. Two hundred and twenty FRALLE2000T-treated patients were
      tested retrospectively for NOTCH1/FBXW7/RAS and PTEN alterations. Patients with
      NOTCH1/FBXW7 (N/F) mutations and RAS/PTEN (R/P) germ line (GL) were classified as
      oncogenetic low risk (gLoR; n = 111), whereas those with N/F GL and R/P GL
      mutations or N/F and R/P mutations were classified as high risk (gHiR; n = 109).
      Day 35 MRD status was available for 191 patients. Five-year cumulative incidence
      of relapse (CIR) and disease-free survival were 36% and 60% for gHiR patients and
      11% and 89% for gLoR patients, respectively. Importantly, among the 60% of
      patients with MRD <10-4, 5-year CIR was 29% for gHiR patients and 4% for gLoR
      patients. Based on multivariable Cox models and stepwise selection, the 3 most
      discriminating variables were the oncogenetic classifier, MRD, and white blood
      cell (WBC) count. Patients harboring a WBC count >=200 * 109/L, gHiR classifier,
      and MRD >=10-4 demonstrated a 5-year CIR of 46%, whereas the 58 patients (30%)
      with a WBC count <200 * 109/L, gLoR classifier, and MRD <10-4 had a very low risk
      of relapse, with a 5-year CIR of only 2%. In childhood T-ALL, the N/F/R/P
      mutation profile is an independent predictor of relapse. When combined with MRD
      and a WBC count >=200 * 109/L, it identifies a significant subgroup of patients
      with a low risk of relapse.

PMID- 29051183
TI  - Development of T-cell immunotherapy for hematopoietic stem cell transplantation
      recipients at risk of leukemia relapse.
AB  - Leukemia relapse remains the major cause of allogeneic hematopoietic stem cell
      transplantation (HCT) failure, and the prognosis for patients with post-HCT
      relapse is poor. There is compelling evidence that potent selective antileukemic
      effects can be delivered by donor T cells specific for particular minor
      histocompatibility (H) antigens. Thus, T-cell receptors (TCRs) isolated from
      minor H antigen-specific T cells represent an untapped resource for developing
      targeted T-cell immunotherapy to manage post-HCT leukemic relapse. Recognizing
      that several elements may be crucial to the efficacy and safety of engineered T
      cell immunotherapy, we developed a therapeutic transgene with 4 components: (1) a
      TCR specific for the hematopoietic-restricted, leukemia-associated minor H
      antigen, HA-1; (2) a CD8 coreceptor to promote function of the class I-restricted
      TCR in CD4+ T cells; (3) an inducible caspase 9 safety switch to enable
      elimination of the HA-1 TCR T cells in case of toxicity; and (4) a CD34-CD20
      epitope to facilitate selection of the engineered cell product and tracking of
      transferred HA-1 TCR T cells. The T-cell product includes HA-1 TCR CD4+ T cells
      to augment the persistence and function of the HA-1 TCR CD8+ T cells and includes
      only memory T cells; naive T cells are excluded to limit the potential for
      alloreactivity mediated by native TCR coexpressed by HA-1 TCR T cells. We
      describe the development of this unique immunotherapy and demonstrate functional
      responses to primary leukemia by CD4+ and CD8+ T cells transduced with a
      lentiviral vector incorporating the HA-1 TCR transgene construct.

PMID- 29051184
TI  - Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for
      children with sickle cell anemia.
AB  - Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA)
      living in high-resource malaria-free regions, but its safety and efficacy in
      malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists,
      remain unknown. In vitro studies suggest hydroxyurea could increase malaria
      severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM
      (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized,
      double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda,
      comparing hydroxyurea to placebo at 20 +/- 2.5 mg/kg per day for 12 months. The
      primary outcome was incidence of clinical malaria. Secondary outcomes included
      SCA-related adverse events (AEs), clinical and laboratory effects, and
      hematological toxicities. Children received either hydroxyurea (N = 104) or
      placebo (N = 103). Malaria incidence did not differ between children on
      hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02,
      0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the
      hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61).
      Time to infection also did not differ significantly between treatment arms. A
      composite SCA-related clinical outcome (vaso-occlusive painful crisis,
      dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion)
      was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children
      receiving hydroxyurea had significantly increased hemoglobin concentration and
      fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs,
      sepsis episodes, and dose-limiting toxicities were similar between treatment
      arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria).
      Hydroxyurea treatment appears safe for children with SCA living in malaria
      endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs.
      Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal
      dosing and monitoring regimens for Africa remain undefined. This trial was
      registered at www.clinicaltrials.gov as #NCT01976416.

PMID- 29051185
TI  - cGMP-Elevating Compounds and Ischemic Conditioning Provide Cardioprotection
      Against Ischemia and Reperfusion Injury via Cardiomyocyte-Specific BK Channels.
AB  - BACKGROUND: The nitric oxide-sensitive guanylyl cyclase/cGMP-dependent protein
      kinase type I signaling pathway can afford protection against the
      ischemia/reperfusion injury that occurs during myocardial infarction. Reportedly,
      voltage and Ca2+-activated K+ channels of the BK type are stimulated by cGMP/cGMP
      dependent protein kinase type I, and recent ex vivo studies implicated that
      increased BK activity favors the survival of the myocardium at
      ischemia/reperfusion. It remains unclear, however, whether the molecular events
      downstream of cGMP involve BK channels present in cardiomyocytes or in other
      cardiac cell types. METHODS: Gene-targeted mice with a cardiomyocyte- or smooth
      muscle cell-specific deletion of the BK (CMBK or SMBK knockouts) were subjected
      to the open-chest model of myocardial infarction. Infarct sizes of the
      conditional mutants were compared with litter-matched controls, global BK
      knockout, and wild-type mice. Cardiac damage was assessed after mechanical
      conditioning or pharmacological stimulation of the cGMP pathway and by using
      direct modulators of BK. Long-term outcome was studied with respect to heart
      functions and cardiac fibrosis in a chronic myocardial infarction model. RESULTS:
      Global BK knockouts and CMBK knockouts, in contrast with SMBK knockouts,
      exhibited significantly larger infarct sizes compared with their respective
      controls. Ablation of CMBK resulted in higher serum levels of cardiac troponin I
      and elevated amounts of reactive oxygen species, lower phosphorylated
      extracellular receptor kinase and phosphorylated AKT levels and an increase in
      myocardial apoptosis. Moreover, CMBK was required to allow beneficial effects of
      both nitric oxide-sensitive guanylyl cyclase activation and inhibition of the
      cGMP-degrading phosphodiesterase-5, ischemic preconditioning, and
      postconditioning regimens. To this end, after 4 weeks of reperfusion, fibrotic
      tissue increased and myocardial strain echocardiography was significantly
      compromised in CMBK-deficient mice. CONCLUSIONS: Lack of CMBK channels renders
      the heart more susceptible to ischemia/reperfusion injury, whereas the
      pathological events elicited by ischemia/reperfusion do not involve BK in
      vascular smooth muscle cells. BK seems to permit the protective effects triggered
      by cinaciguat, riociguat, and different phosphodiesterase-5 inhibitors and
      beneficial actions of ischemic preconditioning and ischemic postconditioning by a
      mechanism stemming primarily from cardiomyocytes. This study establishes
      mitochondrial CMBK channels as a promising target for limiting acute cardiac
      damage and adverse long-term events that occur after myocardial infarction.

PMID- 29051188
TI  - Rapid change of liver stiffness after variceal ligation and TIPS implantation.
AB  - Liver stiffness (LS) as measured by transient elastography is widely used to
      screen for liver fibrosis. However, LS also increases in response to pressure
      changes like congestion but no data on portal pressure are available. We study
      here the effect of rapid portal pressure changes on LS. Therefore, LS was
      assessed directly prior and after ligation of esophageal varices ( n = 11) as
      well as transjugular intrahepatic portosystemic shunt (TIPS) implantation in
      patients with established cirrhosis ( n = 14). Additionally, we retrospectively
      analyzed changes in LS and variceal size in patients with sequential gastroscopic
      monitoring and LS measurements ( n = 14). To study LS and portal pressure in
      healthy livers, LS (uFibroscan; Echosens, Paris, France) and invasive pressures
      (Powerlab, AD Instruments, New Zealand) were assessed in male Wistar rats after
      ligation of single liver lobes. Ligation of esophageal varices caused an
      immediate and significant increase of LS from 40.3 +/- 19.0 to 56.1 +/- 21.5 kPa.
      Likewise, LS decreased significantly from 53.1 +/- 16.6 to 43.8 +/- 17.3 kPa
      after TIPS placement, which correlated significantly with portal pressure ( r =
      0.558). In the retrospective cohort, the significant LS decrease from 54.9 +/-
      23.5 to 47.9 +/- 23.8 kPa over a mean observation interval of 4.3 +/- 3 mo was
      significantly correlated with a concomitant increase of variceal size ( r = 
      0.605). In the animal model, LS and portal pressure increased significantly after
      single lobe ligation without changes of arterial or central venous pressure. In
      conclusion, rapid changes of portal pressure are a strong modulator of LS in
      healthy and cirrhotic organs. In patients with stable cirrhosis according to the
      model for end-stage liver disease (MELD), a decrease of LS may be indicative for
      enlarging varices. NEW & NOTEWORTHY Liver stiffness (LS) immediately increases
      after variceal ligation while it decreases after transjugular intrahepatic
      portosystemic shunt (TIPS) implantation due to portal pressure changes. LS and
      portal pressure rapidly increase after single lobe ligation in Wistar rats
      without changes of arterial or central venous pressure. Collateral formation may
      be one cause for a transient decrease in LS in the absence of other confounders.
      Such pressure changes should be considered when interpreting LS in clinical
      practice.

PMID- 29051187
TI  - In vivo magnetofection: a novel approach for targeted topical delivery of nucleic
      acids for rectoanal motility disorders.
AB  - In these studies, we developed a novel approach of in vivo magnetofection for
      localized delivery of nucleic acids such as micro-RNA-139-5p (miR-139-5p; which
      is known to target Rho kinase2) to the circular smooth muscle layer of the
      internal anal sphincter (IAS). The IAS tone is known to play a major role in the
      rectoanal continence via activation of RhoA-associated kinase (RhoA/ROCK2). These
      studies established an optimized protocol for efficient gene delivery using an
      assembly of equal volumes of in vivo PolyMag and miR139-5p or anti-miR-139-5p
      (100 nM each) injected in the circular smooth muscle layer in the pinpointed
      areas of the rat perianal region and then incubated for 20 min under magnetic
      field. Magnetofection efficiency was confirmed and analyzed by confocal
      microscopy of FITC-tagged siRNA. Using physiological and biochemical approaches,
      we investigated the effects of miR-139-5p and anti-miR-139-5p on basal
      intraluminal IAS pressure (IASP), fecal pellet count, IAS tone, agonist-induced
      contraction, contraction-relaxation kinetics, and RhoA/ROCK2 signaling. Present
      studies demonstrate that magnetofection-mediated miR-139-5p delivery
      significantly decreased RhoA/ROCK2, p-MYPT1, and p-MLC20 signaling, leading to
      decreases in the basal IASP and IAS tone and in rates of contraction and
      relaxation associated with increase in fecal pellet output. Interestingly, anti
      miR-139-5p transfection had opposite effects on these parameters. Collectively,
      these data demonstrate that magnetofection is a promising novel method of in vivo
      gene delivery and of nucleotides to the internal anal sphincter for the site
      directed and targeted therapy for rectoanal motility disorders. NEW & NOTEWORTHY
      These studies for the first time demonstrate the success of topical in vivo
      magnetofection (MF) of nucleic acids using perianal injections. To demonstrate
      its effectiveness, we used FITC-tagged siRNA via immunofluorescence microcopy and
      functional and biochemical evidence using miR-139-5p (which is known to target
      ROCK2). In conclusion, MF allows safe, convenient, efficient, and targeted
      delivery of oligonucleotides such as siRNAs and microRNAs. These studies have
      direct therapeutic implications in rectoanal motility disorders especially
      associated with IAS.

PMID- 29051186
TI  - Distinct roles of intracellular heat shock protein 70 in maintaining
      gastrointestinal homeostasis.
AB  - The inducible heat shock protein 70 (Hsp70) is both cytoprotective and
      immunomodulatory, potentially accounting for its critical role in maintaining
      gastrointestinal homeostasis. When levels are reduced in conditions like
      inflammatory bowel diseases (IBD), loss of function contributes to the severity
      and chronicity of these diseases, although through which cell types and
      mechanisms remains unclear. Here, the role of Hsp70-mediated intestinal
      epithelial protection and immune regulation in experimental colitis was examined
      by using a villin promoter-driven Hsp70 transgene in the 2,4,6-trinitrobenzene
      sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models and in IL-10/Hsp70
      double knockout (IL10-/-/Hsp70-/-) mice. In addition, Hsp70-mediated IL-10
      production and immune protection were investigated using a CD45RBhigh transfer
      model and measuring colonic and immune cell cytokine expression during colitis.
      We found that the epithelial-specific expression of Hsp70 transgene attenuated
      DSS-induced colitis in Hsp70-/- mice by protecting tight junctions (TJ) and their
      interaction with the TJ-associated protein ZO-1. In the TNBS colitis and
      CD45RBhigh model, Hsp70 carried out its intracellular anti-inflammatory function
      by maintaining IL-10 production. Impaired ERK phosphorylation, but not p38 or JNK
      phosphorylation pathways, was associated with decreased IL-10 production in Hsp70
      deficient cells. Together, these actions can be leveraged in the context of
      cellular specificity to develop complementary strategies that can lead to
      reduction in mucosal injury and immune activation in colonic colitis development.
      NEW & NOTEWORTHY Using four different experimental colitis models, we filled an
      important gap in knowledge by defining essential roles of intracellular heat
      shock protein 70 in different cell types in maintaining intestinal integrity and
      immune regulation. These findings are relevant to human inflammatory bowel
      diseases and represent potential avenues for developing therapeutic strategies,
      not only to counter the destructive processes of inflammation but also to promote
      tissue healing and prevent complications frequently associated with chronic
      intestinal inflammation.

PMID- 29051189
TI  - KLF-5 extends its fingers to desmosomes: the next frontier for enteric epithelial
      research?

PMID- 29051191
TI  - Role of thyroid hormone in skeletal muscle physiology.
AB  - Thyroid hormones (TH) are crucial for development, growth, differentiation,
      metabolism and thermogenesis. Skeletal muscle (SM) contractile function,
      myogenesis and bioenergetic metabolism are influenced by TH. These effects depend
      on the presence of the TH transporters MCT8 and MCT10 in the plasma membrane, the
      expression of TH receptors (THRA or THRB) and hormone availability, which is
      determined either by the activation of thyroxine (T4) into triiodothyronine (T3)
      by type 2 iodothyronine deiodinases (D2) or by the inactivation of T4 into
      reverse T3 by deiodinases type 3 (D3). SM relaxation and contraction rates depend
      on T3 regulation of myosin expression and energy supplied by substrate oxidation
      in the mitochondria. The balance between D2 and D3 expression determines TH
      intracellular levels and thus influences the proliferation and differentiation of
      satellite cells, indicating an important role of TH in muscle repair and
      myogenesis. During critical illness, changes in TH levels and in THR and
      deiodinase expression negatively affect SM function and repair. This review will
      discuss the influence of TH action on SM contraction, bioenergetics metabolism,
      myogenesis and repair in health and illness conditions.

PMID- 29051190
TI  - Molecular Basis of Overdominance at a Flower Color Locus.
AB  - Single-gene overdominance is one of the major mechanisms proposed to explain
      heterosis (i.e., hybrid vigor), the phenomenon that hybrid offspring between two
      inbred lines or varieties show superior phenotypes to both parents. Although
      sporadic examples of single-gene overdominance have been reported over the
      decades, the molecular nature of this phenomenon remains poorly understood and it
      is unclear whether any generalizable principle underlies the various cases.
      Through bulk segregant analysis, chemical profiling, and transgenic experiments,
      we show that loss-of-function alleles of the FLAVONE SYNTHASE (FNS) gene cause
      overdominance in anthocyanin-based flower color intensity in the monkeyflower
      species Mimulus lewisii FNS negatively affects flower color intensity by
      competing with the anthocyanin biosynthetic enzymes for the same substrates, yet
      positively affects flower color intensity by producing flavones, the colorless
      copigments required for anthocyanin stabilization, leading to enhanced
      pigmentation in the heterozyote (FNS/fns) relative to both homozygotes (FNS/FNS
      and fns/fns). We suggest that this type of antagonistic pleiotropy (i.e., alleles
      with opposing effects on different components of the phenotypic output) might be
      a general principle underlying single-gene overdominance.

PMID- 29051192
TI  - Animal models to explore the effects of glucocorticoids on skeletal growth and
      structure.
AB  - Glucocorticoids (GCs) are effective for the treatment of many chronic conditions,
      but their use is associated with frequent and wide-ranging adverse effects
      including osteoporosis and growth retardation. The mechanisms that underlie the
      undesirable effects of GCs on skeletal development are unclear, and there is no
      proven effective treatment to combat them. An in vivo model that investigates the
      development and progression of GC-induced changes in bone is, therefore,
      important and a well-characterized pre-clinical model is vital for the evaluation
      of new interventions. Currently, there is no established animal model to
      investigate GC effects on skeletal development and there are pros and cons to
      consider with the different protocols used to induce osteoporosis and growth
      retardation. This review will summarize the literature and highlight the models
      and techniques employed in experimental studies to date.

PMID- 29051193
TI  - Taking responsibility for the unrealistic expectations about frailty.

PMID- 29051195
TI  - Management of paediatric hernia.

PMID- 29051194
TI  - Haploid Selection Favors Suppressed Recombination Between Sex Chromosomes Despite
      Causing Biased Sex Ratios.
AB  - To date, research on the evolution of sex chromosomes has focused on sexually
      antagonistic selection among diploids, which has been shown to be a potent driver
      of the strata and reduced recombination that characterize many sex chromosomes.
      However, significant selection can also occur on haploid genotypes during less
      conspicuous life cycle stages, e.g., competition among sperm/pollen or meiotic
      drive during gamete/spore production. These haploid selective processes are
      typically sex-specific, e.g., gametic/gametophytic competition typically occurs
      among sperm/pollen, and meiotic drive typically occurs during either
      spermatogenesis or oogenesis. We use models to investigate whether sex-specific
      selection on haploids could drive the evolution of recombination suppression on
      the sex chromosomes, as has been demonstrated for sex-specific selection among
      diploids. A potential complication is that zygotic sex-ratios become biased when
      haploid selected loci become linked to the sex-determining region because the
      zygotic sex ratio is determined by the relative number and fitness of X- vs. Y
      bearing sperm. Despite causing biased zygotic sex-ratios, we find that a period
      of sex-specific haploid selection generally favors recombination suppression on
      the sex chromosomes. Suppressed recombination is favored because it allows
      associations to build up between haploid-beneficial alleles and the sex that
      experiences haploid selection most often (e.g., pollen beneficial alleles become
      strongly associated with the male determining region, Y or Z). Haploid selected
      loci can favor recombination suppression even in the absence of selective
      differences between male and female diploids. Overall, we expand our view of the
      sex-specific life cycle stages that can drive sex chromosome evolution to include
      gametic competition and meiotic drive. Based on our models, sex chromosomes
      should become enriched for genes that experience haploid selection, as is
      expected for genes that experience sexually antagonistic selection. Thus, we
      generate a number of predictions that can be evaluated in emerging sex chromosome
      systems.

PMID- 29051196
TI  - Mechanisms of Phosphorus Acquisition and Lipid Class Remodeling under P
      Limitation in a Marine Microalga.
AB  - Molecular mechanisms of phosphorus (P) limitation are of great interest for
      understanding algal production in aquatic ecosystems. Previous studies point to P
      limitation-induced changes in lipid composition. As, in microalgae, the molecular
      mechanisms of this specific P stress adaptation remain unresolved, we reveal a
      detailed phospholipid-recycling scheme in Nannochloropsis oceanica and describe
      important P acquisition genes based on highly corresponding transcriptome and
      lipidome data. Initial responses to P limitation showed increased expression of
      genes involved in P uptake and an expansion of the P substrate spectrum based on
      purple acid phosphatases. Increase in P trafficking displayed a rearrangement
      between compartments by supplying P to the chloroplast and carbon to the cytosol
      for lipid synthesis. We propose a novel phospholipid-recycling scheme for algae
      that leads to the rapid reduction of phospholipids and synthesis of the P-free
      lipid classes. P mobilization through membrane lipid degradation is mediated
      mainly by two glycerophosphoryldiester phosphodiesterases and three patatin-like
      phospholipases A on the transcriptome level. To compensate for low phospholipids
      in exponential growth, N. oceanica synthesized sulfoquinovosyldiacylglycerol and
      diacylglyceroltrimethylhomoserine. In this study, it was shown that an N.
      oceanica strain has a unique repertoire of genes that facilitate P acquisition
      and the degradation of phospholipids compared with other stramenopiles. The novel
      phospholipid-recycling scheme opens new avenues for metabolic engineering of
      lipid composition in algae.

PMID- 29051197
TI  - Photo-Oxidative Stress during Leaf, Flower and Fruit Development.

PMID- 29051198
TI  - Abscisic Acid-Induced Reactive Oxygen Species Are Modulated by Flavonols to
      Control Stomata Aperture.
AB  - Abscisic acid (ABA) increases reactive oxygen species (ROS) in guard cells to
      close Arabidopsis (Arabidopsis thaliana) stomata. In tomato (Solanum
      lycopersicum), we find that ABA-increased ROS is followed by stomatal closure and
      that both responses are blocked by inhibitors of ROS-producing respiratory burst
      oxidase enzymes. ABA-induced ROS sensor fluorescence accumulates in the nucleus,
      chloroplasts, and endomembranes. The accumulation of flavonol antioxidants in
      guard cells, but not surrounding pavement cells, was visualized by confocal
      microscopy using a flavonol-specific fluorescent dye. Decreased flavonols in
      guard cells in the anthocyanin reduced (are) mutant and elevated levels in the
      anthocyanin without (aw) mutant were quantified by confocal microscopy and in
      leaf extracts by mass spectrometry. Consistent with flavonols acting as
      antioxidants, higher levels of ROS were detected in guard cells of the tomato are
      mutant and lower levels were detected in aw both at homeostasis and after
      treatment with ABA. These results demonstrate the inverse relationship between
      flavonols and ROS. Guard cells of are show greater ABA-induced closure than the
      wild type, reduced light-dependent guard cell opening, and reduced water loss,
      with aw having opposite responses. Ethylene treatment of wild-type tomato plants
      increased flavonol accumulation in guard cells; however, no flavonol increases
      were observed in Neverripe (Nr), an ethylene receptor mutant. Consistent with
      lower levels of ROS due to elevated flavonols, ethylene treatments decreased ABA
      induced stomatal closure in the wild type, but not Nr, with ethylene responses
      attenuated in the are mutant. Together, these results are consistent with
      flavonols dampening the ABA-dependent ROS burst that drives stomatal closure and
      facilitating stomatal opening to modulate leaf gas exchange.

PMID- 29051202
TI  - Health Care Economics: A Study Guide for Neuroradiology Fellows, Part 2.
AB  - In this second article, we continue the review of current health care economics
      as it relates to radiologists, specifically framed by topics defined by the
      Accreditation Council for Graduate Medical Education in the evaluation of
      neuroradiology fellows. The discussion in this article is focused on topics
      pertaining to levels 4 and 5, which are the more advanced levels of competency
      defined by the Accreditation Council for Graduate Medical Education
      Neuroradiology Milestones on Health Care Economics and System Based Practice.

PMID- 29051199
TI  - Assessment and comparison of thermal stability of phosphorothioate-DNA, DNA, RNA,
      2'-F RNA, and LNA in the context of Phi29 pRNA 3WJ.
AB  - The question of whether RNA is more stable or unstable compared to DNA or other
      nucleic acids has long been a subject of extensive scrutiny and public attention.
      Recently, thermodynamically stable and degradation-resistant RNA motifs have been
      utilized in RNA nanotechnology to build desired architectures and integrate
      multiple functional groups. Here we report the effects of phosphorothioate
      deoxyribonucleotides (PS-DNA), deoxyribonucleotides (DNA), ribonucleotides (RNA),
      2'-F nucleotides (2'-F), and locked nucleic acids (LNA) on the thermal and in
      vivo stability of the three-way junction (3WJ) of bacteriophage phi29 motor
      packaging RNA. It was found that the thermal stability gradually increased
      following the order of PS-DNA/PS-DNA < DNA/DNA < DNA/RNA < RNA/RNA < RNA/2'-F RNA
      < 2'-F RNA/2'-F RNA < 2'-F RNA/LNA < LNA/LNA. This proposition is supported by
      studies on strand displacement and the melting of homogeneous and heterogeneous
      3WJs. By simply mixing different chemically modified oligonucleotides, the
      thermal stability of phi29 pRNA 3WJ can be tuned to cover a wide range of melting
      temperatures from 21.2 degrees C to over 95 degrees C. The 3WJLNA was resistant
      to boiling temperature denaturation, urea denaturation, and 50% serum
      degradation. Intravenous injection of fluorescent LNA/2'-F hybrid 3WJs into mice
      revealed its exceptional in vivo stability and presence in urine. It is thus
      concluded that incorporation of LNA nucleotides, alone or in combination with 2'
      F, into RNA nanoparticles derived from phi29 pRNA 3WJ can extend the half-life of
      the RNA nanoparticles in vivo and improve their pharmacokinetics profile.

PMID- 29051204
TI  - Imaging Appearances and Pathologic Characteristics of Spinal Epidural Meningioma.
AB  - BACKGROUND AND PURPOSE: Spinal epidural meningioma is an uncommon tumor. This
      study aimed to analyze the imaging and pathologic characteristics of this rare
      tumor. MATERIALS AND METHODS: Fourteen confirmed cases of epidural meningioma
      were retrospectively reviewed, and imaging characteristics and pathologic
      findings were analyzed to identify the typical features. RESULTS: The mean age of
      the patients (4 men, 10 women) was 44.9 years. Twelve tumors were in the cervical
      spinal canal, and 2, in the thoracic spinal canal. There were 9 en plaque
      meningiomas, 4 dumbbell-shaped meningiomas, and 1 fusiform/ovoid meningioma. The
      epidural meningiomas extended over 2-5 spinal segments (mean, 3.2 spinal
      segments). A soft epidural mass was seen in 12/14 (86%) patients. Dural
      calcification was seen in 8/14 (57%) tumors. Tumor caused intervertebral foramen
      enlargement in 10/14 (71%) patients and adhered to the nerve roots in 11/14 (79%)
      patients. Intradural invasion was seen in 8/14 (57%) patients. The dural tail
      sign was present in 13/14 (93%) tumors on contrast-enhanced T1WI. Regarding
      pathologic type, 10 of 14 (71%) were psammomatous, 2 of 14 (14%) were
      meningothelial, 1 of 14 (7%) was angiomatous, and 1 of 14 (7%) was transitional.
      During follow-up (mean follow-up, 73.4 months; range, 4-192 months), 7 patients
      had recurrence. Recurrences were between 4 and 192 months after the operation.
      CONCLUSIONS: Epidural meningioma has 3 different growth patterns. Dural
      thickening, calcification, invasion, and epidural mass formation are
      characteristic features of epidural meningioma. Regular follow-up imaging is
      required to detect recurrence.

PMID- 29051200
TI  - Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre
      mRNAs and various non-coding RNAs.
AB  - N6-methyladenosine (m6A) is a highly dynamic RNA modification that has recently
      emerged as a key regulator of gene expression. While many m6A modifications are
      installed by the METTL3-METTL14 complex, others appear to be introduced
      independently, implying that additional human m6A methyltransferases remain to be
      identified. Using crosslinking and analysis of cDNA (CRAC), we reveal that the
      putative human m6A "writer" protein METTL16 binds to the U6 snRNA and other
      ncRNAs as well as numerous lncRNAs and pre-mRNAs. We demonstrate that METTL16 is
      responsible for N6-methylation of A43 of the U6 snRNA and identify the early U6
      biogenesis factors La, LARP7 and the methylphosphate capping enzyme MEPCE as
      METTL16 interaction partners. Interestingly, A43 lies within an essential ACAGAGA
      box of U6 that base pairs with 5' splice sites of pre-mRNAs during splicing,
      suggesting that METTL16-mediated modification of this site plays an important
      role in splicing regulation. The identification of METTL16 as an active m6A
      methyltransferase in human cells expands our understanding of the mechanisms by
      which the m6A landscape is installed on cellular RNAs.

PMID- 29051203
TI  - Anterior Circulation Acute Ischemic Stroke Associated with Atherosclerotic
      Lesions of the Cervical ICA: A Nosologic Entity Apart.
AB  - BACKGROUND AND PURPOSE: Mechanical thrombectomy for patients with acute ischemic
      stroke with tandem occlusions has been shown to present varying reperfusion
      successes and clinical outcomes. However, the heterogeneity of tandem occlusion
      etiology has been strongly neglected in previous studies. We retrospectively
      investigated patients with acute ischemic stroke atherothrombotic tandem
      occlusion. MATERIALS AND METHODS: All consecutive patients with acute ischemic
      stroke with atherothrombotic tandem occlusions treated with mechanical
      thrombectomy in our center between September 2009 and April 2015 were analyzed.
      They were compared with patients with acute ischemic stroke with dissection
      related tandem occlusion and isolated intracranial occlusion treated during the
      same period. Comparative univariate and multivariate analyses were conducted,
      including demographic data, safety, and rates of successful recanalization and
      good clinical outcome. RESULTS: Despite comparable baseline severity of
      neurologic deficits and infarct core extension, patients with atherothrombotic
      tandem occlusions were older (P < .001), were more frequently smokers (P < .001),
      and had globally more cardiovascular risk factors (P < .001) than the other 2
      groups of patients. The patients with atherothrombotic tandem occlusions had
      significantly longer procedural times (P < .001), lower recanalization rates (P =
      .004), and higher global burden of procedural complications (P < .001). In this
      group, procedural complications (OR = 0.15, P = .02) and the TICI 2b/3
      reperfusion scores (OR = 17.76, P = .002) were independently predictive factors
      of favorable clinical outcome. CONCLUSIONS: Our study suggests that
      atherothrombotic tandem occlusions represent a peculiar and different nosologic
      entity compared with dissection-related tandem occlusions. This challenging cause
      of acute ischemic stroke should be differentiated from other etiologies in
      patient management in future prospective studies.

PMID- 29051205
TI  - Two-Center Experience in the Endovascular Treatment of Ruptured and Unruptured
      Intracranial Aneurysms Using the WEB Device: A Retrospective Analysis.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of the Woven EndoBridge (WEB)
      device for the treatment of cerebral aneurysms has been investigated in several
      studies. Our objective was to report the experience of 2 neurovascular centers
      with the WEB device in the treatment of broad-based intracranial aneurysms,
      including the technical feasibility and safety as well as short- and midterm
      angiographic and clinical follow-up-results. MATERIALS AND METHODS: We performed
      a retrospective analysis of all ruptured and unruptured aneurysms treated with a
      WEB device (WEB Single-Layer and Single-Layer Sphere) between August 2014 and
      February 2017. Primary outcome measures included the feasibility of implantation
      and the angiographic outcome. Secondary outcome measures included the clinical
      outcome at discharge and procedural complications. RESULTS: One hundred two
      aneurysms in 101 patients, including 37 (36.3%) ruptured aneurysms, were treated
      with the WEB device. Implantation was successful in 98 (96.1%) aneurysms.
      Additional devices (stents/coils) were necessary in 15.3% (15/98) of aneurysms.
      Procedural complications occurred in 4.9% (5/102). Of these, 4 were
      thromboembolic events and 1 was an intraprocedural rupture. Angiographic follow
      up at 3 and 12 months was available for 79.6% (78/98) and 50.0% (49/98) of all
      aneurysms to date, respectively, showing a sufficient aneurysm occlusion in 80.7%
      (63/78) at 3 months and 77.6% (38/49) at 12 months. Delayed aneurysm ruptures
      have not been observed during the follow-up period to date. CONCLUSIONS: The WEB
      device offers a safe and effective treatment option for broad-based intracranial
      aneurysms without the need for dual antiplatelet therapy.

PMID- 29051206
TI  - Reply.

PMID- 29051207
TI  - Multiparametric Imaging Improves Confidence in the Diagnosis of Multinodular and
      Vacuolating Neuronal Tumor of the Cerebrum.

PMID- 29051209
TI  - Erratum.

PMID- 29051208
TI  - Redefining the Pulvinar Sign in Fabry Disease.
AB  - BACKGROUND AND PURPOSE: The pulvinar sign refers to exclusive T1WI hyperintensity
      of the lateral pulvinar. Long considered a common sign of Fabry disease, the
      pulvinar sign has been reported in many pathologic conditions. The exact
      incidence of the pulvinar sign has never been tested in representative cohorts of
      patients with Fabry disease. The aim of this study was to assess the prevalence
      of the pulvinar sign in Fabry disease by analyzing T1WI in a large Fabry disease
      cohort, determining whether relaxometry changes could be detected in this region
      independent of the pulvinar sign positivity. MATERIALS AND METHODS: We
      retrospectively analyzed brain MR imaging of 133 patients with Fabry disease
      recruited through specialized care clinics. A subgroup of 26 patients underwent a
      scan including 2 FLASH sequences for relaxometry that were compared with MRI
      scans of 34 healthy controls. RESULTS: The pulvinar sign was detected in 4 of 133
      patients with Fabry disease (3.0%). These 4 subjects were all adult men (4 of 53,
      7.5% of the entire male population) with renal failure and under enzyme
      replacement therapy. When we tested for discrepancies between Fabry disease and
      healthy controls in quantitative susceptibility mapping and relaxometry maps, no
      significant difference emerged for any of the tested variables. CONCLUSIONS: The
      pulvinar sign has a significantly lower incidence in Fabry disease than
      previously described. This finding, coupled with a lack of significant
      differences in quantitative MR imaging, allows hypothesizing that selective
      involvement of the pulvinar is a rare neuroradiologic sign of Fabry disease.

PMID- 29051210
TI  - Selective Poststent Balloon Angioplasty for Carotid Stenting.

PMID- 29051211
TI  - Reply.

PMID- 29051212
TI  - A young man with severe acute haemolytic anaemia.

PMID- 29051213
TI  - Changes in Statin Adherence Following an Acute Myocardial Infarction Among Older
      Adults: Patient Predictors and the Association With Follow-Up With Primary Care
      Providers and/or Cardiologists.
AB  - BACKGROUND: Hospitalizations for acute myocardial infarctions (AMIs) are
      associated with changes in statin adherence. It is unclear to what extent
      adherence changes, which patients are likely to change, and how post-discharge
      follow-up is associated with statin adherence change. METHODS AND RESULTS: This
      retrospective study used Medicare data for all fee-for-service beneficiaries 66
      years and older with an AMI hospitalization in 2008-2010 and statin use before
      their index AMI. Multivariable multinomial logistic regression models (odds ratio
      [OR] and 99% confidence interval [CI]) were applied to assess associations
      between both patient characteristics and follow-up with a primary care provider
      and/or cardiologist with the outcome of statin adherence change (increase or
      decrease) from the 6-month pre- to 6-month post-AMI periods. Of 113 296 patients,
      64.0% had no change in adherence, while 19.7% had increased and 16.3% had
      decreased adherence after AMI hospitalization. Black and Hispanic patients were
      more likely to have either increased or decreased adherence than white patients.
      Patients who required coronary artery bypass graft surgery (OR, 1.34; 99% CI,
      1.21-1.49) or percutaneous transluminal coronary angioplasty/stent procedure (OR,
      1.25; 99% CI, 1.17-1.32) during their index hospitalization were more likely to
      have increased adherence. Follow-up with a primary care provider was only mildly
      associated with increased adherence (OR, 1.08; 99% CI, 1.00-1.16), while follow
      up with a cardiologist (OR, 1.15; 99% CI, 1.05-1.25) or both provider types (OR,
      1.21; 99% CI, 1.12-1.30) had stronger associations with increased adherence.
      CONCLUSIONS: Post-AMI changes in statin adherence varied by patient
      characteristics, and improved adherence was associated with post-discharge follow
      up care, particularly with a cardiologist or both a primary care provider and a
      cardiologist.

PMID- 29051214
TI  - 24-Hour Blood Pressure Variability Assessed by Average Real Variability: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Although 24-hour blood pressure (BP) variability (BPV) is predictive
      of cardiovascular outcomes independent of absolute BP levels, it is not regularly
      assessed in clinical practice. One possible limitation to routine BPV assessment
      is the lack of standardized methods for accurately estimating 24-hour BPV. We
      conducted a systematic review to assess the predictive power of reported BPV
      indexes to address appropriate quantification of 24-hour BPV, including the
      average real variability (ARV) index. METHODS AND RESULTS: Studies chosen for
      review were those that presented data for 24-hour BPV in adults from meta
      analysis, longitudinal or cross-sectional design, and examined BPV in terms of
      the following issues: (1) methods used to calculate and evaluate ARV; (2)
      assessment of 24-hour BPV determined using noninvasive ambulatory BP monitoring;
      (3) multivariate analysis adjusted for covariates, including some measure of BP;
      (4) association of 24-hour BPV with subclinical organ damage; and (5) the
      predictive value of 24-hour BPV on target organ damage and rate of cardiovascular
      events. Of the 19 assessed studies, 17 reported significant associations between
      high ARV and the presence and progression of subclinical organ damage, as well as
      the incidence of hard end points, such as cardiovascular events. In all these
      cases, ARV remained a significant independent predictor (P<0.05) after adjustment
      for BP and other clinical factors. In addition, increased ARV in systolic BP was
      associated with risk of all cardiovascular events (hazard ratio, 1.18; 95%
      confidence interval, 1.09-1.27). Only 2 cross-sectional studies did not find that
      high ARV was a significant risk factor. CONCLUSIONS: Current evidence suggests
      that ARV index adds significant prognostic information to 24-hour ambulatory BP
      monitoring and is a useful approach for studying the clinical value of BPV.

PMID- 29051216
TI  - Prolyl 4-Hydroxylase Domain Protein 3 Overexpression Improved Obstructive Sleep
      Apnea-Induced Cardiac Perivascular Fibrosis Partially by Suppressing Endothelial
      to-Mesenchymal Transition.
AB  - BACKGROUND: Intermittent hypoxia (IH) induced by obstructive sleep apnea is the
      key factor involved in cardiovascular fibrosis. Under persistent hypoxia
      condition, endothelial cells respond by endothelial-to-mesenchymal transition
      (EndMT), which is associated with cardiovascular fibrosis. Prolyl 4-hydroxylase
      domain protein 3 (PHD3) is a cellular oxygen sensor and its expression increased
      in hypoxia. However, its role in obstructive sleep apnea-induced EndMT and
      cardiovascular fibrosis is still uncertain. We investigated the potential
      mechanism of obstructive sleep apnea-induced cardiac perivascular fibrosis and
      the role of PHD3 in it. METHODS AND RESULTS: In vivo, C56BL/6 mice were exposed
      to IH for 12 weeks. PHD3 expression was changed by lentivirus-mediated short
      hairpin PHD3 and lentivirus carrying PHD3 cDNA. EndMT related protein levels,
      histological and functional parameters were detected after 12 weeks. In vitro,
      human umbilical vein endothelial cells were treated with IH/short-hairpin
      PHD3/lentivirus carrying PHD3 cDNA to explore the mechanism of PHD3 in altered
      function of human umbilical vein endothelial cells. We found that chronic
      intermittent hypoxia increase PHD3 expression and EndMT. In vivo, IH accelerate
      cardiac dysfunction and aggravate collagen deposition via the process of EndMT.
      And, when PHD3 were overexpressed, cardiac dysfunction and collagen excessive
      deposition were improved. In vitro, IH induced EndMT, which endow human umbilical
      vein endothelial cells spindle morphology and an enhanced ability to migration
      and collagen secretion. PHD3 overexpression in cultured human umbilical vein
      endothelial cells ameliorated IH-induced EndMT through inactivating hypoxia
      inducible factor 1 alpha and small mothers against decapentaplegic 2 and 3.
      CONCLUSIONS: Obstructive sleep apnea-induced cardiac perivascular fibrosis is
      associated with EndMT, and PHD3 overexpression might be beneficial in the
      prevention of it by inhibiting EndMT. PHD3 overexpression might have therapeutic
      potential in the treatment of the disease.

PMID- 29051215
TI  - Kinome and Transcriptome Profiling Reveal Broad and Distinct Activities of
      Erlotinib, Sunitinib, and Sorafenib in the Mouse Heart and Suggest Cardiotoxicity
      From Combined Signal Transducer and Activator of Transcription and Epidermal
      Growth Factor Receptor Inhibition.
AB  - BACKGROUND: Most novel cancer therapeutics target kinases that are essential to
      tumor survival. Some of these kinase inhibitors are associated with
      cardiotoxicity, whereas others appear to be cardiosafe. The basis for this
      distinction is unclear, as are the molecular effects of kinase inhibitors in the
      heart. METHODS AND RESULTS: We administered clinically relevant doses of
      sorafenib, sunitinib (cardiotoxic multitargeted kinase inhibitors), or erlotinib
      (a cardiosafe epidermal growth factor receptor inhibitor) to mice daily for 2
      weeks. We then compared the effects of these 3 kinase inhibitors on the cardiac
      transcriptome using RNAseq and the cardiac kinome using multiplexed inhibitor
      beads coupled with mass spectrometry. We found unexpectedly broad molecular
      effects of all 3 kinase inhibitors, suggesting that target kinase selectivity
      does not define either the molecular response or the potential for
      cardiotoxicity. Using in vivo drug administration and primary cardiomyocyte
      culture, we also show that the cardiosafety of erlotinib treatment may result
      from upregulation of the cardioprotective signal transducer and activator of
      transcription 3 pathway, as co-treatment with erlotinib and a signal transducer
      and activator of transcription inhibitor decreases cardiac contractile function
      and cardiomyocyte fatty acid oxidation. CONCLUSIONS: Collectively our findings
      indicate that preclinical kinome and transcriptome profiling may predict the
      cardiotoxicity of novel kinase inhibitors, and suggest caution for the proposed
      therapeutic strategy of combined signal transducer and activator of
      transcription/epidermal growth factor receptor inhibition for cancer treatment.

PMID- 29051217
TI  - Management of Persistent Angina After Myocardial Infarction Treated With
      Percutaneous Coronary Intervention: Insights From the TRANSLATE-ACS Study.
AB  - BACKGROUND: Angina has important implications for patients' quality of life and
      healthcare utilization. Angina management after acute myocardial infarction (MI)
      treated with percutaneous coronary intervention (PCI) is unknown. METHODS AND
      RESULTS: TRANSLATE-ACS (Treatment With Adenosine Diphosphate Receptor Inhibitors:
      Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary
      Syndrome) was a longitudinal study of MI patients treated with percutaneous
      coronary intervention at 233 US hospitals from 2010 to 2012. Among patients with
      self-reported angina at 6 weeks post-MI, we described patterns of angina and
      antianginal medication use through 1 year postdischarge. Of 10 870 percutaneous
      coronary intervention-treated MI patients, 3190 (29.3%) reported angina symptoms
      at 6 weeks post-MI; of these, 658 (20.6%) had daily/weekly angina while 2532
      (79.4%) had monthly angina. Among patients with 6-week angina, 2936 (92.0%)
      received beta-blockers during the 1 year post-MI, yet only 743 (23.3%) were
      treated with other antianginal medications. At 1 year, 1056 patients (33.1%) with
      6-week angina reported persistent angina symptoms. Of these, only 31.2% had been
      prescribed non-beta-blocker antianginal medications at any time in the past year.
      Among patients undergoing revascularization during follow-up, only 25.9% were on
      >=1 non-beta-blocker anti-anginal medication at the time of the procedure.
      CONCLUSIONS: Angina is present in one third of percutaneous coronary intervention
      treated MI patients as early as 6 weeks after discharge, and many of these
      patients have persistent angina at 1 year. Non-beta-blocker antianginal
      medications are infrequently used in these patients, even among those with
      persistent angina and those undergoing revascularization.

PMID- 29051218
TI  - Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient
      Ischemic Attack: The CHANCE Study (Clopidogrel in High-Risk Patients With Acute
      Nondisabling Cerebrovascular Events).
AB  - BACKGROUND AND PURPOSE: We aimed to determine the association between stress
      hyperglycemia and risk of new stroke in patients with a minor ischemic stroke or
      transient ischemic attack. METHODS: A subgroup of 3026 consecutive patients from
      73 prespecified sites of the CHANCE trial (Clopidogrel in High-Risk Patients With
      Acute Nondisabling Cerebrovascular Events) were analyzed. Stress hyperglycemia
      was measured by glucose/glycated albumin (GA) ratio. Glucose/GA ratio was
      calculated by fasting plasma glucose divided by GA and categorized into 4 even
      groups according to the quartiles. The primary outcome was a new stroke (ischemic
      or hemorrhagic) at 90 days. We assessed the association between glucose/GA ratio
      and risk of stroke by multivariable Cox regression models adjusted for potential
      covariates. RESULTS: Among 3026 patients included, a total of 299 (9.9%) new
      stroke occurred at 3 months. Compared with patients with the lowest quartile,
      patients with the highest quartile of glucose/GA ratio was associated with an
      increased risk of stroke at 3 months after adjusted for potential covariates
      (12.0% versus 9.2%; adjusted hazard ratio, 1.46; 95% confidence interval, 1.06
      2.01). Similar results were observed after further adjusted for fasting plasma
      glucose. We also observed that higher level of glucose/GA ratio was associated
      with an increased risk of stroke with a threshold of 0.29 using a Cox regression
      model with restricted cubic spline. CONCLUSIONS: Stress hyperglycemia, measured
      by glucose/GA ratio, was associated with an increased risk of stroke in patients
      with a minor ischemic stroke or transient ischemic attack. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

PMID- 29051219
TI  - It Is Difficult to Make Predictions, Especially About the Future.

PMID- 29051220
TI  - Letter by Vester et al Regarding Article, "Hope Dies Last-Evidence Again Fails to
      Support a Neuroprotectant: Cerebrolysin for Acute Ischemic Stroke".

PMID- 29051221
TI  - Response by Bereczki to Letter Regarding Article, "Hope Dies Last-Evidence Again
      Fails to Support a Neuroprotectant: Cerebrolysin for Acute Ischemic Stroke".

PMID- 29051222
TI  - Development and Validation of a Predictive Model for Functional Outcome After
      Stroke Rehabilitation: The Maugeri Model.
AB  - BACKGROUND AND PURPOSE: Prediction of outcome after stroke rehabilitation may
      help clinicians in decision-making and planning rehabilitation care. We developed
      and validated a predictive tool to estimate the probability of achieving
      improvement in physical functioning (model 1) and a level of independence
      requiring no more than supervision (model 2) after stroke rehabilitation.
      METHODS: The models were derived from 717 patients admitted for stroke
      rehabilitation. We used multivariable logistic regression analysis to build each
      model. Then, each model was prospectively validated in 875 patients. RESULTS:
      Model 1 included age, time from stroke occurrence to rehabilitation admission,
      admission motor and cognitive Functional Independence Measure scores, and
      neglect. Model 2 included age, male gender, time since stroke onset, and
      admission motor and cognitive Functional Independence Measure score. Both models
      demonstrated excellent discrimination. In the derivation cohort, the area under
      the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913
      (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow chi2 was
      4.12 (P=0.249) and 1.20 (P=0.754), respectively. In the validation cohort, the
      area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model
      1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer
      Lemeshow chi2 was 8.86 (P=0.115) and 34.50 (P=0.001), respectively. Both
      improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P=0.001) and
      a level of independence requiring no more than supervision (hazard ratios, 0.32;
      0.14-0.68; P=0.004) were independently associated with improved 4-year survival.
      A calculator is freely available for download at https://goo.gl/fEAp81.
      CONCLUSIONS: This study provides researchers and clinicians with an easy-to-use,
      accurate, and validated predictive tool for potential application in
      rehabilitation research and stroke management.

PMID- 29051223
TI  - CRISPR/Cas-based screening of long non-coding RNAs (lncRNAs) in macrophages with
      an NF-kappaB reporter.
AB  - The innate immune system protects against infections by initiating an inducible
      inflammatory response. NF-kappaB is one of the critical transcription factors
      controlling this complex response, but some aspects of its regulation remain
      unclear. For example, although long non-coding RNAs (lncRNAs) have been shown to
      critically regulate gene expression, only a fraction of these have been
      functionally characterized, and the extent to which lncRNAs control NF-kappaB
      expression is unknown. Here, we describe the generation of a GFP-based NF-kappaB
      reporter system in immortalized murine bone marrow-derived macrophages (iBMDM).
      Activation of this reporter, using Toll-like receptor ligands, resulted in GFP
      expression, which could be monitored by flow cytometry. We also established a
      CRISPR/Cas9 gene deletion system in this NF-kappaB reporter line, enabling us to
      screen for genes that regulate NF-kappaB signaling. Our deletion-based approach
      identified two long intergenic non-coding(linc)RNAs, lincRNA-Cox2 and lincRNA
      AK170409, that control NF-kappaB signaling. We demonstrate a potential novel role
      for lincRNA-Cox2 in promoting IkappaBalpha degradation in the cytoplasm. For
      lincRNA-AK170409, we provide evidence that this nuclearly-localized lincRNA
      regulates a number of inflammation-related genes. In conclusion, we have
      established an NF-kappaB-GFP iBMDM reporter cell line and a line that stably
      expresses Cas9. Our approach enabled the identification of lincRNA-Cox2 and
      lincRNA-AK170409 as NF-kappaB regulators, and this tool will be useful for
      identifying additional genes involved in regulating this transcription factor
      critical for immune function.

PMID- 29051225
TI  - Strong association between corticosterone levels and temperature-dependent
      metabolic rate in individual zebra finches.
AB  - Glucocorticoid hormones (GCs) are often assumed to be indicators of stress. At
      the same time, one of their fundamental roles is to facilitate metabolic
      processes to accommodate changes in energetic demands. Although the metabolic
      function of GCs is thought to be ubiquitous across vertebrates, we are not aware
      of experiments which tested this directly, i.e. in which metabolic rate was
      manipulated and measured together with GCs. We therefore tested for a
      relationship between plasma corticosterone (CORT; ln transformed) and metabolic
      rate (MR; measured using indirect calorimetry) in a between- and within
      individual design in captive zebra finches (Taeniopygia guttata) of both sexes.
      In each individual, CORT and MR were measured at two different temperature
      levels: 'warm' (22 degrees C) and 'cold' (12 degrees C). CORT and MR were both
      increased in colder compared with warmer conditions within individuals, but also
      across individuals. At the between-individual level, we found a positive
      relationship between CORT and MR, with an accelerating slope towards higher MR
      and CORT values. In contrast, the within-individual changes in CORT and MR in
      response to colder conditions were linearly correlated between individuals. The
      CORT-MR relationship did not differ between the sexes. Our results illustrate the
      importance of including variation at different levels to better understand
      physiological modulation. Furthermore, our findings support the interpretation of
      CORT variation as an indicator of metabolic needs.

PMID- 29051224
TI  - Advanced glycation end products impair NLRP3 inflammasome-mediated innate immune
      responses in macrophages.
AB  - Advanced glycation end products (AGEs) are adducts formed on proteins by
      glycation with reducing sugars, such as glucose, and tend to form and accumulate
      under hyperglycemic conditions. AGE accumulation alters protein function and has
      been implicated in the pathogenesis of many degenerative diseases such as
      diabetic complications. AGEs have also been shown to promote the production of
      pro-inflammatory cytokines, but the roles of AGEs in inflammasome signaling have
      not been explored in detail. Here, we present evidence that AGEs attenuate
      activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs)
      as determined by caspase-1 processing and interleukin-1beta production. AGEs also
      dampened the assembly of the NLRP3 inflammasome, but did not affect the NLRC4 or
      AIM2 inflammasome activation. Moreover, our data indicated that AGE treatment
      inhibited Toll-like receptor (TLR)-dependent production of pro-inflammatory
      cytokines in BMDMs. This immunosuppressive effect of AGE was not associated with
      a receptor for AGEs (RAGE)-mediated signaling. Instead, AGE treatment markedly
      suppressed lipopolysaccharide-induced M1 polarization of macrophages.
      Furthermore, AGEs significantly dampened innate immune responses including NLRP3
      inflammasome activation and type-I interferon production in macrophages upon
      influenza virus infection. These observations collectively suggest that AGEs
      could impair host NLRP3 inflammasome-mediated innate immune defenses against RNA
      virus infection leading to an increased susceptibility to infection.

PMID- 29051226
TI  - Thermal tachypnea in avian embryos.
AB  - Many adult mammals and birds respond to high surrounding temperatures with
      thermal tachypnea - an increase in breathing frequency accompanied by shallow
      tidal volume, with minimal increase in oxygen consumption (VO2 ). This pattern
      favors heat dissipation by evaporative water loss (EWL) through the respiratory
      tract. We asked to what extent this response was apparent at the earliest stages
      of development, when pulmonary ventilation initiates. Measurements of pulmonary
      ventilation (VE; barometric technique), VO2  (open-flow methodology) and EWL
      (water scrubbers) were performed on chicken embryos at the earliest appearance of
      pulmonary ventilation, during the internal pipping stage. Data were collected,
      first, at the normal incubation temperature (37.5 degrees C); then, ambient and
      egg temperatures were increased to approximately 44 degrees C over a 2 h period.
      Other embryos of the same developmental stage (controls) were maintained in
      normothermia for the whole duration of the experiment. During heat exposure, the
      embryo's VO2  and carbon dioxide production increased little. In contrast, VE
      more than doubled (~128% increase), entirely because of the large rise in
      breathing frequency (~132% increase), with no change in tidal volume. EWL did not
      change significantly, probably because, within the egg, the thermal and water
      vapor gradients are almost nonexistent. We conclude that chicken embryos respond
      to a major heat load with tachypnea, like many adult mammals and birds do. Its
      appearance so early in development, although ineffective for heat loss, signifies
      that thermal tachypnea represents an important breathing response necessary to be
      functional from hatching.

PMID- 29051227
TI  - Fighting over burrows: the emergence of dominance hierarchies in the Norway
      lobster (Nephrops norvegicus).
AB  - Animals fight over resources such as mating partners, territory, food or shelter
      and repeated contests lead to stable social hierarchies in different phyla. The
      group dynamics of hierarchy formation are not characterized in the Norway lobster
      (Nephrops norvegicus). Lobsters spend most of the day in burrows and forage
      outside of them according to a diel (i.e. 24 h-based) activity rhythm. Here, we
      use a linear and generalized mixed model approach to analyse, in seven groups of
      four male lobsters, the formation of dominance hierarchies and rank-related
      changes in burrowing behaviour. We show that hierarchies emerge within 1-3 days
      and increase in steepness over a period of 5 days, while rank changes and number
      of fights gradually decrease over a 5-day period. The rank position determined by
      open area fights predicts the outcome of fights over burrows, the time spent in
      burrows, and the locomotor activity levels. Dominant lobsters are more likely to
      evict subordinate lobsters from their burrows and are more successful in
      defending their own burrows. They spend more time in burrows and display lower
      levels of locomotor activity outside the burrow. Lobsters do not change their
      diel activity rhythms as a result of a change in rank, and all tested individuals
      showed higher activity at night and dusk compared with dawn and daytime. We
      discuss how behavioural changes in burrowing behaviour could lead to rank-related
      benefits such as reduced exposure to predators and energy savings.

PMID- 29051228
TI  - Thermal strategies of king penguins during prolonged fasting in water.
AB  - Most animals experience periods of unfavourable conditions, challenging their
      daily energy balance. During breeding, king penguins fast voluntarily for up to
      1.5 months in the colony, after which they replenish their energy stores at sea.
      However, at sea, birds might encounter periods of low foraging profitability,
      forcing them to draw from previously stored energy (e.g. subcutaneous fat).
      Accessing peripheral fat stores requires perfusion, increasing heat loss and
      thermoregulatory costs. Hence, how these birds balance the conflicting demands of
      nutritional needs and thermoregulation is unclear. We investigated the
      physiological responses of king penguins to fasting in cold water by: (1)
      monitoring tissue temperatures, as a proxy of tissue perfusion, at four distinct
      sites (deep and peripheral); and (2) recording their oxygen consumption rate
      while birds floated inside a water tank. Despite frequent oscillations,
      temperatures of all tissues often reached near-normothermic levels, indicating
      that birds maintained perfusion to peripheral tissues throughout their fasting
      period in water. The oxygen consumption rate of birds increased with fasting
      duration in water, while it was also higher when the flank tissue was warmer,
      indicating greater perfusion. Hence, fasting king penguins in water maintained
      peripheral perfusion, despite the associated greater heat loss and, therefore,
      thermoregulatory costs, probably to access subcutaneous fat stores. Hence, the
      observed normothermia in peripheral tissues of king penguins at sea, upon
      completion of a foraging bout, is likely explained by their nutritional needs:
      depositing free fatty acids (FFA) in subcutaneous tissues after profitable
      foraging or mobilizing FFA to fuel metabolism when foraging success was
      insufficient.

PMID- 29051229
TI  - Channel surfing uncovers a dual-use transporter.

PMID- 29051231
TI  - "Progressive dwindling" or "terminal decline" and end of life care.

PMID- 29051232
TI  - Complete Genome Sequence of Rathayibacter toxicus Phage NCPPB3778.
AB  - The phage NCPPB3778 was isolated from Rathayibacter toxicus strain CS14, and the
      genomic DNA was sequenced. The genome is similar to siphoviruses, consisting of
      44,520 bases including 77 predicted open reading frames. Portions of the genome
      are annotated as typical phage proteins, but much of the genome sequence is
      unique from other bacteriophages.

PMID- 29051230
TI  - iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of
      neurological diseases.
AB  - Disease modeling with induced pluripotent stem cells (iPSCs) is creating an
      abundance of phenotypic information that has become difficult to follow and
      interpret. Here, we report a systematic analysis of research practices and
      reporting bias in neurological disease models from 93 published articles. We find
      heterogeneity in current research practices and a reporting bias toward certain
      diseases. Moreover, we identified 663 CNS cell-derived phenotypes from 243
      patients and 214 controls, which varied by mutation type and developmental stage
      in vitro We clustered these phenotypes into a taxonomy and characterized these
      phenotype-genotype relationships to generate a phenogenetic map that revealed
      novel correlations among previously unrelated genes. We also find that
      alterations in patient-derived molecular profiles associated with cellular
      phenotypes, and dysregulated genes show predominant expression in brain regions
      with pathology. Last, we developed the iPS cell phenogenetic map project atlas
      (iPhemap), an open submission, online database to continually catalog disease
      phenotypes. Overall, our findings offer new insights into the phenogenetics of
      iPSC-derived models while our web tool provides a platform for researchers to
      query and deposit phenotypic information of neurological diseases.

PMID- 29051233
TI  - High-Quality Whole-Genome Sequences of the Oligo-Mouse-Microbiota Bacterial
      Community.
AB  - The Oligo-Mouse-Microbiota (Oligo-MM12) is a community of 12 mouse intestinal
      bacteria to be used for microbiome research in gnotobiotic mice. We present here
      the high-quality whole genome sequences of the Oligo-MM12 strains, which were
      obtained by combining the accuracy of the Illumina platforms with the long reads
      of the PacBio technology.

PMID- 29051234
TI  - Draft Genome Sequence of a Salmonella enterica Serovar Typhi Strain Resistant to
      Fourth-Generation Cephalosporin and Fluoroquinolone Antibiotics.
AB  - Typhoid is endemic in developing countries. We report here the first draft genome
      sequence of a Salmonella enterica serovar Typhi clinical isolate from Pakistan
      exhibiting resistance to cefepime (a fourth-generation cephalosporin) and
      fluoroquinolone antibiotics, two of the last-generation therapies against this
      pathogen. The genome is ~4.8 Mb, with two putative plasmids.

PMID- 29051235
TI  - Complete Genome Sequence of Escherichia Phage OSYSP.
AB  - Bacteriophage OSYSP is a new anti-Escherichia coli O157:H7 phage isolated from
      municipal wastewater in Ohio. OSYSP is potent against enterohemorrhagic E. coli
      and is a candidate biocontrol agent for food and therapeutic applications. In
      this paper, we present the important genetic features of this phage based on its
      complete genome sequence.

PMID- 29051236
TI  - First Complete Genome Sequence of Methicillin-Resistant Staphylococcus aureus
      Strain SO-1977 Isolated from Khartoum, Sudan.
AB  - Methicillin-resistant Staphylococcus aureus is increasingly becoming resistant to
      most antibiotics and consequently has become a challenging public health problem
      in Sudan. The present study documented the first complete genome sequence of
      strain SO-1977, isolated from a contaminated wound in Sudan.

PMID- 29051237
TI  - Whole-Genome Sequence of a Megasphaera elsdenii Strain Isolated from the Gut of a
      Healthy Indian Adult Subject.
AB  - Megasphaera elsdenii has been previously reported in the gut of ruminating
      animals. Its role as an animal probiotic is being investigated, specifically from
      the perspective of enhancing animal productivity. Herein, we report the draft
      genome sequence of M. elsdenii strain indica isolated from the stool sample of a
      healthy Indian subject.

PMID- 29051238
TI  - Draft Genome Sequence of an Atypical Highly Virulent Rabbit Staphylococcus aureus
      Strain.
AB  - Rabbit staphylococcosis is one of the most important diseases in industrial
      rabbit production. We report here the draft genome sequence of Staphylococcus
      aureus strain 380/11, an atypical highly virulent (aHV) rabbit Staphylococcus
      aureus strain.

PMID- 29051239
TI  - Whole-Genome Sequencing of a Human Clinical Isolate of the Novel Species
      Klebsiella quasivariicola sp. nov.
AB  - In a study of 1,777 Klebsiella strains, we discovered KPN1705, which was distinct
      from all recognized Klebsiella spp. We closed the genome of strain KPN1705 using
      a hybrid of Illumina short-read and Oxford Nanopore long-read technologies. For
      this novel species, we propose the name Klebsiella quasivariicola sp. nov.

PMID- 29051240
TI  - Draft Genome Sequence of a Sporulating and Motile Strain of Lachnotalea glycerini
      Isolated from Water in Quebec City, Canada.
AB  - Lachnotalea glycerini CCRI-19302 belongs to the genus Lachnotalea The strain was
      isolated from a water sample harvested in Quebec City, Canada. The genome
      assembly comprised 4,694,231 bp, with 34.6% GC content. This is the first
      documentation to report the genome sequence of a sporulating and motile strain of
      L. glycerini.

PMID- 29051241
TI  - Genome Sequences of Crimean-Congo Hemorrhagic Fever Virus Strains Isolated in
      South Africa, Namibia, and Turkey.
AB  - We report here the full-length sequences of 16 historical isolates of Crimean
      Congo hemorrhagic fever orthonairovirus (CCHFV) obtained in Turkey, Namibia, and
      South Africa. The strains may be useful for future work to develop molecular
      diagnostics or viral evolution studies.

PMID- 29051242
TI  - Complete Genome Sequences of Four Foot-and-Mouth Disease Viruses of Serotype
      South African Territories 1 (SAT 1), Topotype X, Isolated from Cattle in Nigeria
      in 2015.
AB  - The complete genome sequences of four foot-and-mouth disease viruses of South
      African territories 1 (SAT 1) serotype are reported. These viruses originate from
      an outbreak in Nigeria in 2015 and belong to the novel SAT 1 topotype X from the
      west and central African virus pool.

PMID- 29051243
TI  - Genome Sequence of an Endophytic Fungus, Fusarium solani JS-169, Which Has
      Antifungal Activity.
AB  - An endophytic fungus, Fusarium solani strain JS-169, isolated from a mulberry
      twig, showed considerable antifungal activity. Here, we report the draft genome
      sequence of this strain. The assembly comprises 17 scaffolds, with an N50 value
      of 4.93 Mb. The assembled genome was 45,813,297 bp in length, with a G+C content
      of 49.91%.

PMID- 29051244
TI  - Draft Genome Sequences of One Methicillin-Sensitive and Seven Methicillin
      Resistant Staphylococcus aureus Sequence Type 5 Isolates Obtained in California.
AB  - Staphylococcus aureus is a commensal bacterium of humans that can cause a
      spectrum of diseases. An isolate's capacity to cause disease is partially
      attributed to the acquisition of novel mobile genetic elements. This report
      provides the draft genome sequence of one methicillin-susceptible and seven
      methicillin-resistant clinical human S. aureus isolates.

PMID- 29051245
TI  - Characterization of Two Bovine viral diarrhea virus Strains Originating from
      Cattle in Tibet, China.
AB  - Here, we report two strains of Bovine viral diarrhea virus (BVDV), named XZ01 and
      XZ02, that were isolated from cattle in Tibet, China. They belong to subgenotype
      1b. This report will help in understanding the molecular characteristics of BVDV
      in Tibetan cattle.

PMID- 29051246
TI  - Complete Genome Sequence of a Colistin-Resistant Escherichia coli Strain
      Harboring mcr-1 on an IncHI2 Plasmid in the United States.
AB  - We report here the incidental detection and complete genome sequence of a urinary
      Escherichia coli strain harboring mcr-1 and resistant to colistin in a New York
      patient returning from Portugal in 2016. This strain, with sequence type 1485
      (ST1485), was a non-extended-spectrum beta-lactamase (ESBL) and non-carbapenemase
      producer and carried the mcr-1 gene on an IncHI2 plasmid.

PMID- 29051247
TI  - Genome Sequence of an Alphaherpesvirus from a Beluga Whale (Delphinapterus
      leucas).
AB  - Beluga whale alphaherpesvirus 1 was isolated from a blowhole swab taken from a
      juvenile beluga whale. The genome is 144,144 bp in size and contains 86 putative
      genes. The virus groups phylogenetically with members of the genus Varicellovirus
      in subfamily Alphaherpesvirinae and is the first alphaherpesvirus sequenced from
      a marine mammal.

PMID- 29051248
TI  - Metagenomic Analysis of Microbial Diversity in Landfill Lysimeter Soil of
      Ghazipur Landfill Site, New Delhi, India.
AB  - We report the soil microbial diversity and functional aspects related to
      degradation of recalcitrant compounds, determined using a metagenomic approach,
      in a landfill lysimeter prepared with soil from Ghazipur landfill site, New
      Delhi, India. Metagenomic analysis revealed the presence and functional diversity
      of complex microbial communities responsible for waste degradation.

PMID- 29051249
TI  - Complete Genome Sequence of Serotype III Streptococcus agalactiae Sequence Type
      17 Strain 874391.
AB  - Here we report the complete genome sequence of Streptococcus agalactiae strain
      874391. This serotype III isolate is a member of the hypervirulent sequence type
      17 (ST-17) lineage that causes a disproportionate number of cases of invasive
      disease in humans and mammals. A brief historical context of the strain is
      discussed.

PMID- 29051250
TI  - Metagenome of the Microbial Community of Anammox Granules in a
      Nitritation/Anammox Wastewater Treatment System.
AB  - We sequenced the metagenome of a granular sludge in a nitritation/anammox
      bioreactor used for the treatment of ammonium-rich wastewater. Proteobacteria,
      Planctomycetes, Bacteroidetes, Chloroflexi, Ignavibacteriae, and Acidobacteria
      were the predominant phyla in the studied bioreactor. Binning of contigs yielded
      a near-complete genome of the dominant anammox bacterium assigned to the
      candidate genus Brocadia.

PMID- 29051251
TI  - Genome Sequences of Salmonella enterica subsp. enterica Serovar Kentucky Sequence
      Type 152 Isolated from Dairy Cows in the United States.
AB  - Salmonella enterica subsp. enterica serovar Kentucky (S. Kentucky) is frequently
      isolated from dairy cows in the United States, but is an infrequent cause of
      human salmonellosis. To investigate the genomic features of S Kentucky strains
      isolated from a single dairy farm, the genomes of eight isolates were sequenced
      and added to the public domain.

PMID- 29051252
TI  - Draft Genome Sequence of Vibrio sp. Strain V1B Isolated from the Gut Microflora
      of the Scallop Argopecten purpuratus.
AB  - A new Vibrio strain, V1B, was isolated from the intestinal tract of the scallop
      Argopecten purpuratus Strain V1B is closely related to the species Vibrio
      inhibens BFLP-10, which has been characterized as showing antagonistic activity
      against pathogenic Vibrio sp. We report here the draft genome of the isolated
      Vibrio sp. strain V1B.

PMID- 29051253
TI  - Complete Mitochondrial Genome of the Human Liver Cancer HA22T Cell Line.
AB  - Liver cancer remains one of the most lethal malignancies worldwide. We sequenced
      the complete mitochondrial genome of a liver cancer HA22T cell line. The
      sequenced mitogenome of 16,603 bp will aid in the use of the HA22T cell line for
      liver cancer study.

PMID- 29051254
TI  - Complete Genome Sequence of Lactobacillus acidophilus Strain ATCC 53544.
AB  - Here we present the complete genome sequence of Lactobacillus acidophilus ATCC
      53544. The assembly contains 1,991,906 bp and is 99.7% similar to L. acidophilus
      NCFM. This strain was isolated from a rectal swab specimen of an infant and has
      previously been used as a feed supplement for animals.

PMID- 29051255
TI  - Complete Genome Sequence of Porcine respirovirus 1 Strain USA/MN25890NS/2016,
      Isolated in the United States.
AB  - A porcine parainfluenza virus type 1 (species Porcine respirovirus 1) cell
      culture isolate, USA/MN25890NS/2016, was obtained from porcine nasal swabs, and
      its complete genome sequence (GenBank accession number MF681710) was determined
      to help further characterize this virus.

PMID- 29051256
TI  - Erratum for Kennedy et al., "Genome Sequences of Three Novel Isolates of Human
      Parainfluenza Virus 2 Associated with Acute Respiratory Infection".

PMID- 29051257
TI  - Draft Genome Sequence of Halophilic Hahella sp. Strain CCB-MM4, Isolated from
      Matang Mangrove Forest in Perak, Malaysia.
AB  - Hahella sp. strain CCB-MM4 is a halophilic bacterium isolated from estuarine
      mangrove sediment. The genome sequence of Hahella sp. CCB-MM4 provides insights
      into exopolysaccharide biosynthesis and the lifestyle of the bacterium thriving
      in a saline mangrove environment.

PMID- 29051258
TI  - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Typhimurium
      Q1.
AB  - Here, we report the draft genome sequence of Salmonella enterica subsp. enterica
      serovar Typhimurium strain Q1. The draft genome contains 4,793,493 bp in 149
      contigs.

PMID- 29051259
TI  - Draft Genome Sequence of a Novel Chitinophaga sp. Strain, MD30, Isolated from a
      Biofilm in an Air Conditioner Condensate Pipe.
AB  - Most of the 24 known Chitinophaga species were originally isolated from soils. We
      report the draft genome sequence of a putatively novel Chitinophaga sp. from a
      biofilm in an air conditioner condensate pipe. The genome comprises 7,661,303 bp
      in one scaffold, 5,694 predicted protein-coding sequences, and a G+C content of
      47.6%.

PMID- 29051260
TI  - Draft Genome Sequence of a Community-Acquired Methicillin-Resistant
      Staphylococcus aureus USA300 Isolate from a River Sample.
AB  - The increasing emergence of multiresistant bacteria in health care settings in
      the community and in the environment represents a major health threat worldwide.
      Here, we report the draft genome sequence of a community-acquired methicillin
      resistant Staphylococcus aureus (CA-MRSA) USA300 isolate (W1) from a small river
      in southern Austria.

PMID- 29051261
TI  - Genome Sequences of Two NDM-1 Metallo-beta-Lactamase-Producing Multidrug
      Resistant Strains of Klebsiella pneumoniae with a High Degree of Similarity, One
      of Which Contains Prophage.
AB  - We report genome sequences of two NDM-1 metallo-beta-lactamase-producing
      multidrug-resistant Klebsiella pneumoniae isolates of sequence type 147 (ST147)
      from one hospital. The genomes are highly similar and differ in prophage located
      in the chromosome of K. pneumoniae KPB-1470/16 and in the additional plasmid
      carrying blaOXA-48 gene in K. pneumoniae KPB-417/16.

PMID- 29051262
TI  - Hepatitis B vaccine shortage: another symptom of chronic neglect?

PMID- 29051263
TI  - So far, yet so close: alpha-Catenin dimers help migrating cells get together.
AB  - Epithelial cells in tissues use their actin cytoskeletons to stick together,
      whereas unattached cells make active plasma membrane protrusions to migrate. In
      this issue, Wood et al. (2017. J. Cell Biol.
      https://doi.org/10.1083/jcb.201612006) show that the junction component alpha
      catenin is critical in freely moving cells to promote adhesion and migration.

PMID- 29051267
TI  - Do admission glucose levels aid in predicting mortality associated with community
      acquired pneumonia?

PMID- 29051265
TI  - Regulation of NOTCH signaling by RAB7 and RAB8 requires carboxyl methylation by
      ICMT.
AB  - Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal
      prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of
      either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-KrasG12D
      mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila
      melanogaster wing vein and scutellar bristle development to screen Rab proteins
      predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8
      as ICMT substrates that when silenced phenocopy ste14 deficiency. ICMT, RAB7, and
      RAB8 were all required for efficient NOTCH1 signaling in mammalian cells.
      Overexpression of RAB8 rescued NOTCH activation after ICMT knockdown both in U2OS
      cells expressing NOTCH1 and in fly wing vein development. ICMT deficiency induced
      mislocalization of GFP-RAB7 and GFP-RAB8 from endomembrane to cytosol, enhanced
      binding to RABGDI, and decreased GTP loading of RAB7 and RAB8. Deficiency of
      ICMT, RAB7, or RAB8 led to mislocalization and diminished processing of NOTCH1
      GFP. Thus, NOTCH signaling requires ICMT in part because it requires methylated
      RAB7 and RAB8.

PMID- 29051266
TI  - SUMOylation of human septins is critical for septin filament bundling and
      cytokinesis.
AB  - Septins are cytoskeletal proteins that assemble into nonpolar filaments. They are
      critical in diverse cellular functions, acting as scaffolds for protein
      recruitment and as diffusion barriers for subcellular compartmentalization. Human
      septins are encoded by 13 different genes and are classified into four groups
      based on sequence homology (SEPT2, SEPT3, SEPT6, and SEPT7 groups). In yeast,
      septins were among the first proteins reported to be modified by SUMOylation, a
      ubiquitin-like posttranslational modification. However, whether human septins
      could be modified by small ubiquitin-like modifiers (SUMOs) and what roles this
      modification may have in septin function remains unknown. In this study, we first
      show that septins from all four human septin groups can be covalently modified by
      SUMOs. We show in particular that endogenous SEPT7 is constitutively SUMOylated
      during the cell cycle. We then map SUMOylation sites to the C-terminal domain of
      septins belonging to the SEPT6 and SEPT7 groups and to the N-terminal domain of
      septins from the SEPT3 group. We finally demonstrate that expression of non
      SUMOylatable septin variants from the SEPT6 and SEPT7 groups leads to aberrant
      septin bundle formation and defects in cytokinesis after furrow ingression.
      Altogether, our results demonstrate a pivotal role for SUMOylation in septin
      filament bundling and cell division.

PMID- 29051268
TI  - What is precision medicine?
AB  - The term "precision medicine" has become very popular over recent years, fuelled
      by scientific as well as political perspectives. Despite its popularity, its
      exact meaning, and how it is different from other popular terms such as
      "stratified medicine", "targeted therapy" or "deep phenotyping" remains unclear.
      Commonly applied definitions focus on the stratification of patients, sometimes
      referred to as a novel taxonomy, and this is derived using large-scale data
      including clinical, lifestyle, genetic and further biomarker information, thus
      going beyond the classical "signs-and-symptoms" approach.While these aspects are
      relevant, this description leaves open a number of questions. For example, when
      does precision medicine begin? In which way does the stratification of patients
      translate into better healthcare? And can precision medicine be viewed as the end
      point of a novel stratification of patients, as implied, or is it rather a
      greater whole?To clarify this, the aim of this paper is to provide a more
      comprehensive definition that focuses on precision medicine as a process. It will
      be shown that this proposed framework incorporates the derivation of novel
      taxonomies and their role in healthcare as part of the cycle, but also covers
      related terms.

PMID- 29051264
TI  - Protein sequestration at the nuclear periphery as a potential regulatory
      mechanism in premature aging.
AB  - Despite the extensive description of numerous molecular changes associated with
      aging, insights into the driver mechanisms of this fundamental biological process
      are limited. Based on observations in the premature aging syndrome Hutchinson
      Gilford progeria, we explore the possibility that protein regulation at the inner
      nuclear membrane and the nuclear lamina contributes to the aging process. In
      support, sequestration of nucleoplasmic proteins to the periphery impacts cell
      stemness, the response to cytotoxicity, proliferation, changes in chromatin
      state, and telomere stability. These observations point to the nuclear periphery
      as a central regulator of the aging phenotype.

PMID- 29051269
TI  - Management and long-term outcomes of sarcoidosis-associated pulmonary
      hypertension.
AB  - Studies reporting the effects of modern strategies with pulmonary arterial
      hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary
      hypertension (S-APH) are limited.Clinical and haemodynamic data from newly
      diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35
      mmHg or mPAP 25-35 mmHg with cardiac index <2.5 L.min-1.m-2) were collected from
      the French Pulmonary Hypertension Registry between 2004 and 2015.Data from 126
      patients with severe S-APH were analysed (mean+/-sd age 57.5+/-11.6 years, 74%
      radiological stage IV). 97 patients (77%) received PAH-targeted therapy and
      immunosuppressive therapy was initiated or escalated in 33 patients at the time
      of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy
      initiation, mean+/-sd pulmonary vascular resistance decreased from 9.7+/-4.4 to
      6.9+/-3.0 Wood units (p<0.001), without significant improvement in exercise
      capacity. Among the 11 patients treated only with immunosuppressive therapy, a
      haemodynamic improvement was observed in four patients, including two with
      compressive lymph nodes. After a median follow-up of 28 months, 39 patients
      needed PAH-targeted therapy escalation, nine underwent lung transplantation and
      42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively.PAH
      targeted therapy improved short-term pulmonary haemodynamics in severe S-APH
      without change in exercise capacity. Immunosuppressive therapy improved
      haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains
      associated with a poor prognosis.

PMID- 29051270
TI  - Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea.
AB  - Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour
      aggressiveness and cancer mortality, as well as greater severity of infections,
      which have been attributed to an immune deregulation. We studied the expression
      of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells
      from patients with OSA, and its consequences on immune-suppressing activity. We
      report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on
      CD8+ T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were
      induced in both the human in vitro and murine models of intermittent hypoxia, as
      well as by hypoxia-inducible factor-1alpha transfection. PD-L1/PD-1 crosstalk
      suppressed T-cell proliferation and activation of autologous T-lymphocytes and
      impaired the cytotoxic activity of CD8+ T-cells. In addition, monocytes from
      patients with OSA exhibited high levels of retinoic acid related orphan receptor,
      which might explain the differentiation of myeloid-derived suppressor cells.
      Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA,
      resulting in a reduction in CD8+ T-cell activation and cytotoxicity, providing
      biological plausibility to the increased incidence and aggressiveness of cancer
      and the higher risk of infections described in these patients.

PMID- 29051272
TI  - Effect of pirfenidone on cough in patients with idiopathic pulmonary fibrosis.

PMID- 29051271
TI  - Combined measurement of carbon monoxide and nitric oxide lung transfer does not
      improve the identification of pulmonary hypertension in systemic sclerosis.
AB  - Screening is important to determine whether patients with systemic sclerosis
      (SSc) have pulmonary hypertension because earlier pulmonary hypertension
      treatment can improve survival in these patients. Although decreased transfer
      factor of the lung for carbon monoxide (TLCO) is currently considered the best
      pulmonary function test for screening for pulmonary hypertension in SSc, small
      series have suggested that partitioning TLCO into membrane conductance (diffusing
      capacity) for carbon monoxide (DMCO) and alveolar capillary blood volume (VC)
      through combined measurement of TLCO and transfer factor of the lung for nitric
      oxide (TLNO) is more effective to identify pulmonary hypertension in SSc patients
      compared with TLCO alone. Here, the objective was to determine whether combined
      TLCO-TLNO partitioned with recently refined equations could more accurately
      detect pulmonary hypertension than TLCO alone in SSc.For that purpose, 572
      unselected consecutive SSc patients were retrospectively recruited in seven
      French centres.Pulmonary hypertension was diagnosed with right heart
      catheterisation in 58 patients. TLCO, TLNO and VC were all lower in SSc patients
      with pulmonary hypertension than in SSc patients without pulmonary hypertension.
      The area under the receiver operating characteristic curve for the presence of
      pulmonary hypertension was equivalent for TLCO (0.82, 95% CI 0.79-0.85) and TLNO
      (0.80, 95% CI 0.76-0.83), but lower for VC (0.75, 95% CI 0.71-0.78) and DMCO
      (0.66, 95% CI 0.62-0.70).Compared with TLCO alone, combined TLCO-TLNO does not
      add capability to detect pulmonary hypertension in unselected SSc patients.

PMID- 29051273
TI  - Xpert MTB/RIF Ultra: the long-awaited game changer for tuberculous meningitis?

PMID- 29051274
TI  - Effect of morphine on breathlessness and exercise endurance in advanced COPD: a
      randomised crossover trial.
AB  - The objective of the present study was to evaluate the effect of morphine on
      exertional breathlessness and exercise endurance in advanced chronic obstructive
      pulmonary disease (COPD).In a randomised crossover trial, we compared the acute
      effect of immediate-release oral morphine versus placebo on physiological and
      perceptual responses during constant-load cardiopulmonary cycle exercise testing
      (CPET) in 20 adults with advanced COPD and chronic breathlessness
      syndrome.Compared with placebo, morphine reduced exertional breathlessness at
      isotime by 1.2+/-0.4 Borg units and increased exercise endurance time by 2.5+/
      0.9 min (both p<=0.014). During exercise at isotime, morphine decreased
      ventilation by 1.3+/-0.5 L.min-1 and breathing frequency by 2.0+/-0.9 breaths.min
      1 (both p<=0.041). Compared with placebo, morphine decreased exertional
      breathlessness at isotime by >=1 Borg unit in 11 participants (responders) and by
      <1 Borg unit in nine participants (non-responders). Baseline participant
      characteristics, including pulmonary function and cardiorespiratory fitness, were
      similar between responders and non-responders. A higher percentage of responders
      versus non-responders stopped incremental CPET due to intolerable breathlessness:
      82 versus 33% (p=0.028).Immediate-release oral morphine improved exertional
      breathlessness and exercise endurance in some, but not all, adults with advanced
      COPD. The locus of symptom-limitation on laboratory-based CPET may help to
      identify patients most likely to benefit from morphine.

PMID- 29051275
TI  - Prospective study of body mass index and risk of sarcoidosis in US women.

PMID- 29051276
TI  - Precision medicine in airway diseases: moving to clinical practice.
AB  - On February 21, 2017, a European Respiratory Society research seminar held in
      Barcelona discussed how to best apply precision medicine to chronic airway
      diseases such as asthma and chronic obstructive pulmonary disease. It is now
      clear that both are complex and heterogeneous diseases, that often overlap and
      that both require individualised assessment and treatment. This paper summarises
      the presentations and discussions that took place during the seminar.
      Specifically, we discussed the need for a new taxonomy of human diseases, the
      role of different players in this scenario (exposome, genes, endotypes,
      phenotypes, biomarkers and treatable traits) and a number of unanswered key
      questions in the field. We also addressed how to deploy airway precision medicine
      in clinical practice today, both in primary and specialised care. Finally, we
      debated the type of research needed to move the field forward.

PMID- 29051277
TI  - Treatment of sarcoidosis-associated pulmonary hypertension: so close, and yet so
      far.

PMID- 29051278
TI  - Morphine to relieve exertional dyspnoea in COPD: myth, dream or reality?

PMID- 29051280
TI  - Panobinostat monotherapy and combination therapy in patients with acute myeloid
      leukemia: results from two clinical trials.

PMID- 29051279
TI  - Expansion of EPOR-negative macrophages besides erythroblasts by elevated EPOR
      signaling in erythrocytosis mouse models.
AB  - Activated erythropoietin (EPO) receptor (EPOR) signaling causes erythrocytosis.
      The important role of macrophages for the erythroid expansion and differentiation
      process has been reported, both in baseline and stress erythropoiesis. However,
      the significance of EPOR signaling for regulation of macrophages contributing to
      erythropoiesis has not been fully understood. Here we show that EPOR signaling
      activation quickly expands both erythrocytes and macrophages in vivo in mouse
      models of primary and secondary erythrocytosis. To mimic the chimeric condition
      and expansion of the disease clone in the polycythemia vera patients, we combined
      Cre-inducible Jak2V617F/+ allele with LysM-Cre allele which expresses in mature
      myeloid cells and some of the HSC/Ps (LysM-Cre;Jak2V617F/+ mice). We also
      generated inducible EPO-mediated secondary erythrocytosis models using Alb-Cre,
      Rosa26-loxP-stop-loxP-rtTA, and doxycycline inducible EPAS1-double point mutant
      (DPM) alleles (Alb-Cre;DPM mice). Both models developed a similar degree of
      erythrocytosis. Macrophages were also increased in both models without increase
      of major inflammatory cytokines and chemokines. EPO administration also quickly
      induced these macrophages in wild-type mice before observable erythrocytosis.
      These findings suggest that EPOR signaling activation could induce not only
      erythroid cell expansion, but also macrophages. Surprisingly, an in vivo genetic
      approach indicated that most of those macrophages do not express EPOR, but
      erythroid cells and macrophages contacted tightly with each other. Given the
      importance of the central macrophages as a niche for erythropoiesis, further
      elucidation of the EPOR signaling mediated-regulatory mechanisms underlying
      macrophage induction might reveal a potential therapeutic target for
      erythrocytosis.

PMID- 29051281
TI  - Cancer in the National Cancer Institute inherited bone marrow failure syndrome
      cohort after fifteen years of follow-up.
AB  - The National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort
      enrolls patients with the four major syndromes: Fanconi anemia, dyskeratosis
      congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome, and follows
      them with a common comprehensive protocol. The current analysis includes more
      than double the numbers of patients and person-years since our first report,
      published in 2010. Patients with Fanconi anemia and dyskeratosis congenita
      developed head and neck and anogenital squamous cell carcinomas at rates that
      were hundreds-fold greater than those of the general population. In competing
      risk analyses the cumulative incidence of severe bone marrow failure, leading to
      stem cell transplantation or death, was more than 70% by age 60. Patients with
      Diamond-Blackfan anemia developed lung, colon, and cervical cancer at rates
      greater than those of the general population. The cumulative incidence of severe
      bone marrow failure in those with Diamond-Blackfan anemia was 50% by age 60. The
      smaller group, with Shwachman-Diamond syndrome, have not as yet developed a
      significant number of solid tumors, but 40% developed bone marrow failure by age
      50. The risk of solid tumors following stem cell transplantation in Fanconi
      anemia and in dyskeratosis congenita was significantly higher than in non
      transplanted patients. There was no clear association of genotype with cancer in
      any of the syndromes. Cancer was most common in Fanconi anemia, followed by
      dyskeratosis congenita; Diamond-Blackfan anemia and Shwachman-Diamond syndrome
      are less cancer-prone, but nonetheless all patients are at increased risks of
      bone marrow failure and specific cancers. clinicaltrials.gov Identifier:
      00027274.

PMID- 29051282
TI  - Small bone marrow adipocytes predict poor prognosis in acute myeloid leukemia.

PMID- 29051285
TI  - Stand up for wild animal welfare.

PMID- 29051289
TI  - 'Understanding pet owners is key to improving exotic pet welfare'.

PMID- 29051292
TI  - Campaign to end the 'cruel practice' of primates as pets.

PMID- 29051283
TI  - Hsp90 inhibition disrupts JAK-STAT signaling and leads to reductions in
      splenomegaly in patients with myeloproliferative neoplasms.

PMID- 29051293
TI  - Government responds to 'Brexit: farm animal welfare'.

PMID- 29051294
TI  - Equine disease surveillance: quarterly summary.
AB  - of surveillance testing, April to June 2017International disease occurrence in
      the second quarter of 2017These are among matters discussed in the most recent
      quarterly equine disease surveillance report, prepared by Defra, the Animal
      Health Trust and the British Equine Veterinary Association.

PMID- 29051295
TI  - Can serum amyloid A concentrations aid diagnosis of synovial sepsis?

PMID- 29051296
TI  - Is the long course loan everything it's cracked up to be?

PMID- 29051297
TI  - Welfare of chickens at slaughter.

PMID- 29051298
TI  - Applications open for One Health travelling fellowship awards.

PMID- 29051299
TI  - Welfare of chickens at slaughter.

PMID- 29051300
TI  - Exploring human and animal health.
AB  - One week studying veterinary public health may not be everyone's cup of tea, but
      as Cambridge vet student Emma Simpson explains, for the eight students who
      attended this year's Veterinary Public Health Association Masterclass in
      Edinburgh, it ticked all the right boxes.

PMID- 29051302
TI  - Diary of a parliamentary intern.
AB  - Two years ago I started my internship at the House of Lords. It was a leap of
      faith that took me far away from the familiar world of small animal clinical
      practice. Now, as I sit to write my final diary piece, I wonder: was it all worth
      it?

PMID- 29051303
TI  - Transport-associated pathway responses in ovine fetal membranes to changes in
      amniotic fluid dynamics.
AB  - Current evidence suggests that amniotic fluid volume (AFV) is actively regulated
      by vesicular transport of amniotic fluid outward across the amnion and into the
      underlying fetal vasculature in the placenta. Our objective was to determine
      whether gene expression profiles of potential stimulators, inhibitors, and
      mediators of vesicular transport are altered in response to changes in
      intramembranous absorption (IMA) rate. Samples of ovine amnion and chorion were
      obtained from fetal sheep with normal, experimentally reduced or increased AFVs
      and IMA rates. Amnion and chorion levels of target mRNAs were determined by RT
      qPCR In the amnion, caveolin-1 and flotillin-1 mRNA levels were unchanged during
      alterations in IMA rate. However, levels of both were significantly higher in
      amnion than in chorion. Tubulin-alpha mRNA levels in the amnion but not in
      chorion were reduced when IMA rate decreased, and amnion levels correlated
      positively with IMA rate (P < 0.05). Dynamin-2 mRNA levels were not altered by
      experimental conditions. Vascular endothelial growth factor (VEGF164 and
      VEGF164b) mRNA levels increased during both increases and decreases in IMA rate,
      whereas soluble Flt-1 levels did not change. Neither HIF-1alpha nor PBEF mRNA
      levels in the amnion were correlated with VEGF164 expression levels and were not
      related to IMA rate. Collectively, our findings suggest that changes in amnion
      microtubule expression may be important in the regulation of transcellular
      vesicular transport of amniotic fluid and thus modulate IMA rate. Further, our
      results are consistent with the concept that the amnion is the rate-limiting
      layer for amniotic fluid transport.

PMID- 29051304
TI  - Consequences of advanced aging on renal function in chronic hyperandrogenemic
      female rat model: implications for aging women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine and reproductive
      disorder in premenopausal women, characterized by hyperandrogenemia, metabolic
      syndrome, and inflammation. Women who had PCOS during their reproductive years
      remain hyperandrogenemic after menopause. The consequence of chronic
      hyperandrogenemia with advanced aging has not been studied to our knowledge. We
      have characterized a model of hyperandrogenemia in female rats and have aged them
      to 22-25 months to mimic advanced aging in hyperandrogenemic women, and tested
      the hypothesis that chronic exposure to hyperandrogenemia with aging has a
      deleterious effect on renal function. Female rats were chronically implanted with
      dihydrotestosterone pellets (DHT 7.5 mg/90 days) that were changed every 85 days
      or placebo pellets, and renal function was measured by clearance methods. Aging
      DHT-treated females had a threefold higher level of DHT with significantly higher
      body weight, mean arterial pressure, left kidney weight, proteinuria, and kidney
      injury molecule-1 (KIM-1), than did age-matched controls. In addition, DHT
      treated-old females had a 60% reduction in glomerular filtration rate, 40%
      reduction in renal plasma flow, and significant reduction in urinary nitrate and
      nitrite excretion (UNOxV), an index of nitric oxide production. Morphological
      examination of kidneys showed that old DHT-treated females had significant focal
      segmental glomerulosclerosis, global sclerosis, and interstitial fibrosis
      compared to controls. Thus chronic hyperandrogenemia that persists into old age
      in females is associated with renal injury. These data suggest that women with
      chronic hyperandrogenemia such as in PCOS may be at increased risk for
      development of chronic kidney disease with advanced age.

PMID- 29051305
TI  - Acoustic change complex in background noise: phoneme level and timing effects.
AB  - The effects of background noise on speech-evoked cortical auditory evoked
      potentials (CAEPs) can provide insight into the physiology of the auditory
      system. The purpose of this study was to determine background noise effects on
      neural coding of different phonemes within a syllable. CAEPs were recorded from
      15 young normal-hearing adults in response to speech signals /s/, /alpha/, and
      /salpha/. Signals were presented at varying signal-to-noise ratios (SNRs). The
      effects of SNR and context (in isolation or within syllable) were analyzed for
      both phonemes. For all three stimuli, latencies generally decreased and
      amplitudes generally increased as SNR improved, and context effects were not
      present; however, the amplitude of the /alpha/ response was the exception,
      showing no SNR effect and a significant context effect. Differential coding of
      /s/ and /alpha/ likely result from level and timing differences. Neural
      refractoriness may result in the lack of a robust SNR effect on amplitude in the
      syllable context. The stable amplitude across SNRs in response to the vowel in
      /salpha/ suggests the combined effects of (1) acoustic characteristics of the
      syllable and noise at poor SNRs and (2) refractory effects resulting from phoneme
      timing at good SNRs. Results provide insights into the coding of multiple-onset
      speech syllables in varying levels of background noise and, together with
      behavioral measures, may help to improve our understanding of speech-perception
      in-noise difficulties.

PMID- 29051306
TI  - Peripheral chemosensitivity is not blunted during 2 h of thermoneutral head out
      water immersion in healthy men and women.
AB  - Carbon dioxide (CO2) retention occurs during water immersion, but it is not known
      if peripheral chemosensitivity is altered during water immersion, which could
      contribute to CO2 retention. We tested the hypothesis that peripheral
      chemosensitivity to hypercapnia and hypoxia is blunted during 2 h of
      thermoneutral head out water immersion (HOWI) in healthy young adults. Peripheral
      chemosensitivity was assessed by the ventilatory, heart rate, and blood pressure
      responses to hypercapnia and hypoxia at baseline, 10, 60, 120 min, and post HOWI
      and a time-control visit (control). Subjects inhaled 1 breath of 13% CO2, 21% O2,
      and 66% N2 to test peripheral chemosensitivity to hypercapnia and 2-6 breaths of
      100% N2 to test peripheral chemosensitivity to hypoxia. Each gas was administered
      four separate times at each time point. Partial pressure of end-tidal CO2
      (PETCO2), arterial oxygen saturation (SpO2), ventilation, heart rate, and blood
      pressure were recorded continuously. Ventilation was higher during HOWI versus
      control at post (P = 0.037). PETCO2 was higher during HOWI versus control at 10
      min (46 +/- 2 vs. 44 +/- 2 mmHg), 60 min (46 +/- 2 vs. 44 +/- 2 mmHg), and 120
      min (46 +/- 3 vs. 43 +/- 3 mmHg) (all P < 0.001). Ventilatory (P = 0.898), heart
      rate (P = 0.760), and blood pressure (P = 0.092) responses to hypercapnia were
      not different during HOWI versus control at any time point. Ventilatory (P =
      0.714), heart rate (P = 0.258), and blood pressure (P = 0.051) responses to
      hypoxia were not different during HOWI versus control at any time point. These
      data indicate that CO2 retention occurs during thermoneutral HOWI despite no
      changes in peripheral chemosensitivity.

PMID- 29051308
TI  - Food engorgement in 35 dogs (2009-2013) compared with 36 dogs with gastric
      dilation and volvulus.
AB  - The clinical features and management of food engorgement (FE) in dogs have not
      been previously described. This retrospective observational study describes
      characteristics and outcome of 35 dogs with FE, and compares features on
      presentation to 36 dogs with gastric dilation and volvulus (GDV). Cases were
      retrospectively reviewed for history, clinical findings and outcome. Gastric
      distension was measured by caudal gastric margin (CGM), level with lumbar
      vertebrae, on a lateral abdominal radiograph. Frequent characteristics of dogs
      with FE included tachycardia, tachypnoea, hyperproteinaemia, increased base
      excess (BE), mild hypernatraemia and hyperlactataemia. There was overlap in CGM
      between dogs with GDV (CGM range L3 to >L6) and dogs with FE (CGM range <L2 to L5
      L6). In contrast to dogs with GDV, lactate concentration in dogs with FE was not
      associated with CGM or BE. Dogs with FE mostly received medical intervention
      consisting of fluid therapy and analgesia, and all dogs survived to discharge. In
      conclusion, dogs with FE frequently presented with acid-base and electrolyte
      derangements, including hyperlactataemia. While dogs with FE can have gastric
      distension as severe as that seen with GDV, outcome with supportive care only is
      excellent.

PMID- 29051307
TI  - Effect of renal denervation on urine angiotensinogen excretion in prenatally
      programmed rats.
AB  - Prenatal programming results in an increase in blood pressure in adult offspring.
      We have shown that compared to control adult offspring whose mothers were fed a
      20% protein diet, programmed adults whose mothers were fed a 6% protein diet
      during the last half of pregnancy have an increase in renal sympathetic nerve
      activity and urinary angiotensinogen/creatinine levels. We hypothesized that the
      increase in urinary angiotensinogen was mediated by renal sympathetic nerve
      activity in programmed rats. In this study performed in 3 month old rats, renal
      denervation resulted in normalization of blood pressure in the 6% programmed
      group (150 +/- 3 Hg in 6% sham vs. 121 +/- 4 Hg in 6% denervated, P < 0.001), and
      a reduction in blood pressure in the 20% group (126 +/- 2 Hg 20% sham vs. 113 +/-
      4 Hg 20% denervated (P < 0.05). We confirm that the intrarenal renin-angiotensin
      system assessed by urinary angiotensinogen/creatinine is upregulated in offspring
      of rats fed a 6% protein diet rats compared to 20% controls. To determine if
      sympathetic nerve activity was mediating the increase in urinary angiotensinogen
      in programmed rats, we compared denervated to sham-operated control and
      programmed rats. Renal denervation had no effect on urinary
      angiotensinogen/creatinine ratio in the 20% group and no effect on the increased
      urinary angiotensinogen/creatinine ratio found in programmed rats. This study
      demonstrates that the increase in urinary angiotensinogen in programmed rats is
      not mediated by renal sympathetic nerve activity.

PMID- 29051309
TI  - Clinical prevalence and associated intraoperative surgical complications of
      reproductive tract lesions in pot-bellied pigs undergoing ovariohysterectomy: 298
      cases (2006-2016).
AB  - To address the current dearth of clinically relevant publications regarding
      ovariohysterectomy (OVH) in the domestic pot-bellied pig (PBP), the present study
      aims to report prevalence of uterine lesions, intraoperative complications, and
      short and long-term survival in this species (n=298). Prevalence of lesions
      included uterine neoplasia 11.4 per cent (34/298), pyometra 1.6 per cent (5/298)
      and cystic endometrial hyperplasia 5 per cent (15/298). Pigs at least six years
      of age were statistically more likely to have a uterine lesion (less than
      P=0.001). Smooth muscle tumours represented the most frequent neoplasm.
      Haemorrhage was the most common intraoperative complication in 23 per cent (8/34)
      of pigs with neoplasia. Pigs without reproductive tract lesions were
      statistically more likely to survive to hospital discharge than those with
      lesions (P=0.001). Short-term survival, defined as survival to hospital
      discharge, of pigs with reproductive tract lesions was 89 per cent (48/54). Pigs
      with pyometra were least likely to survive to discharge 60 per cent (3/5). Long
      term survival (>=1 year) was 93 per cent (14/15) for pigs with neoplasia.
      Practitioners should be aware of significantly higher rate of neoplastic and
      inflammatory diseases in PBP at least six years of age. To minimise morbidity and
      mortality in PBP undergoing OVH, the present study suggests the procedure should
      be performed prior to six years of age.

PMID- 29051310
TI  - Adverse reactions to two intravenous antibiotics (Augmentin and Zinacef) used for
      surgical prophylaxis in dogs.
AB  - Antibiotic prophylaxis in dogs undergoing surgical procedures frequently involves
      the administration of a product without a veterinary licence. Two drugs commonly
      used for this purpose are the clavulanate amoxicillin Augmentin and the
      cefuroxime Zinacef. This prospective observational study aims to compare the
      incidence of adverse events associated with these two antibiotics in a clinical
      setting. The authors hypothesised that a higher incidence of adverse effects
      would be observed with Augmentin. Sixty-five dogs were included in the study and
      adverse events were recorded using a modified scoring system. A significantly
      higher incidence of adverse events to Augmentin (8/22; 36 per cent) was observed
      compared with Zinacef (1/43; 2 per cent) (P=0.0003). The majority of these
      adverse events involved cutaneous signs and/or hypotension. These findings might
      be taken into consideration when selecting one of these intravenous antibiotics
      for prophylaxis in anaesthetised dogs undergoing surgery.

PMID- 29051311
TI  - Quantitative analysis of antibiotic usage in British sheep flocks.
AB  - The aim of this study was to examine the variation in antibiotic usage between
      207 commercial sheep flocks using their veterinary practice prescribing records.
      Mean and median prescribed mass per population corrected unit (mg/PCU) was 11.38
      and 5.95, respectively and closely correlated with animal defined daily dose
      (ADDD) 1.47 (mean), 0.74 (median) (R2=0.84, P<0.001). This is low in comparison
      with the suggested target (an average across all the UK livestock sectors) of 50
      mg/PCU. In total, 80 per cent of all antibiotic usage occurred in the 39 per cent
      of flocks where per animal usage was greater than 9.0 mg/PCU. Parenteral
      antibiotics, principally oxytetracycline, represented 82 per cent of the total
      prescribed mass, 65.5 per cent of antibiotics (mg/PCU) were prescribed for the
      treatment of lameness. Oral antibiotics were prescribed to 49 per cent of flocks,
      64 per cent of predicted lamb crop/farm. Lowland flocks were prescribed
      significantly more antibiotics than hill flocks. Variance partitioning
      apportioned 79 per cent of variation in total antibiotic usage (mg/PCU) to the
      farm level and 21 per cent to the veterinary practice indicating that veterinary
      practices have a substantial impact on overall antimicrobial usage. Reducing
      antibiotic usage in the sheep sector should be possible with better understanding
      of the drivers of high usage in individual flocks and of veterinary prescribing
      practices.

PMID- 29051312
TI  - Myelographic and low-field magnetic resonance imaging findings in dogs with
      presumptive acute hydrated non-compressive nucleus pulposus extrusion.
AB  - MRI is considered gold standard for the diagnosis of presumptive acute hydrated
      non-compressive nucleus pulposus extrusions (AHNCNPE). This retrospective study
      describes the myelographic findings in dogs with AHNCNPE diagnosed by low-field
      MRI and their association with neurological grade, need of surgical decompression
      and outcome. Forty-two myelographies (21 dogs with presumptive AHNCNPE, 21 dogs
      with Hansen type I disc disease herniation) were blindly evaluated. Site of
      herniation, compression pattern, ratio of length of the lesion to length of the
      second lumbar vertebra (LL:L2) and degree of spinal cord compression (SCC) were
      measured on the myelographies of dogs with presumptive AHNCNPE and were compared
      with the corresponding MRI features. Percentage of extruded volume of nucleus
      pulposus (VNP) was calculated on MR images. Myelographic interobserver agreement
      for presumptive diagnosis of AHNCNPE was almost perfect (Io=0.8). Accuracy of
      myelography to detect site of herniation was 80.9 per cent and to identify
      extradural compression was 57.1 per cent. Mean SCC was 5.8A+/-2.6 per cent for
      myelography and 6.6A+/-3 per cent for MRI. Mean LL:L2 ratio was 1.7A+/-0.9 for
      myelography and 1.2A+/-0.8 for MRI. Mean percentage of extruded VNP was 40A+/-14
      per cent, and it was positively associated with neurological grade.

PMID- 29051313
TI  - Anaemia in pet rabbits: causes, severity and reticulocyte response.
AB  - The objective of the study was to determine the causes and the severity of
      anaemia in pet rabbits (Oryctolagus cuniculus), to classify anaemia and to
      compare the reticulocyte counts from healthy and anaemic rabbits. Over a time
      period of 11 years (2000-2011) a retrospective and prospective study of 223 pet
      rabbits was performed. Based on the clinic's own reference range for healthy pet
      rabbits (packed cell volume [PCV] levels 0.33-0.45 l/l), animals with a PCV level
      below 0.33 l/l were considered anaemic. Anaemia was mostly caused by inflammation
      (65/223, 29 per cent) and bleeding (54/223, 24 per cent). Seven per cent (15/223)
      of the rabbits suffered from renal diseases and one rabbit got diagnosed with
      haemolysis caused by liver lobe torsion. In 14 per cent (32/223) of the rabbits
      more than one underlying pathomechanism, like inflammation and bleeding, was
      diagnosed as possible cause of anaemia. In 25 per cent (56/223) of the anaemic
      rabbits no cause was found. Most anaemias were mild (156/223, 70 per cent).
      Moderate (43/223, 19 per cent) or severe (24/223, 11 per cent) anaemia was
      diagnosed more rarely. Anaemic rabbits showed similar reticulocyte counts to
      healthy rabbits with no significant difference. Therefore, a differentiation of
      regenerative and non-regenerative anaemia was not possible.

PMID- 29051314
TI  - Characterisation of porcine circovirus type 2 in porcine circovirus disease cases
      in England and Wales.
AB  - Confirmed cases of porcine circovirus disease (PCVD) in Great Britain have shown
      a steady decline since the availability of porcine circovirus type 2 (PCV2)
      vaccines. However, PCVD is still occasionally diagnosed. The authors carried out
      a genotyping study to characterise PCV2 associated with confirmed PCVD cases in
      England and Wales from 2011 to January 2016 (n=65). A partial fragment of PCV2
      genome encompassing ORF2 was amplified and sequenced from 45 cases of PCVD. The
      majority of sequences were genotype PCV2b but four sequences were PCV2d. The
      significance of the emergence of PCV2d in England and elsewhere in the world is
      not yet known, although it does appear to represent an ongoing global genotype
      shift.

PMID- 29051315
TI  - Future of keeping pet reptiles and amphibians: towards integrating animal
      welfare, human health and environmental sustainability.
AB  - The keeping of exotic pets is currently under debate and governments of several
      countries are increasingly exploring the regulation, or even the banning, of
      exotic pet keeping. Major concerns are issues of public health and safety, animal
      welfare and biodiversity conservation. The keeping of reptiles and amphibians in
      captivity encompasses all the potential issues identified with keeping exotic
      pets, and many of those relating to traditional domestic pets. Within the context
      of risks posed by pets in general, the authors argue for the responsible and
      sustainable keeping of reptile and amphibian pets by private persons, based on
      scientific evidence and on the authors' own expertise (veterinary medicine,
      captive husbandry, conservation biology).

PMID- 29051316
TI  - Profile of pig farms combining high performance and low antimicrobial usage
      within four European countries.
AB  - Pig farmers are strongly encouraged to reduce their antimicrobial usage because
      of the rising threat from antimicrobial resistance. However, such efforts should
      not compromise the herd health status and performance. This study aimed to
      describe the profile of so-called 'top-farms' that managed to combine both high
      technical performance and low antimicrobial usage. A cross-sectional study was
      conducted among 227 farrow-to-finish farms in Belgium, France, Germany and
      Sweden. Among them, 44 farms were allocated to the top-farms group and were
      compared with the 'regular' farms group in terms of farm characteristics,
      biosecurity and health status. Top-farms had fewer gastrointestinal symptoms in
      suckling pigs and fewer respiratory symptoms in fatteners, which could partly
      explain their reduced need for antimicrobials and higher performance. They also
      had higher biosecurity and were located in sparsely populated pig areas. However,
      14 farms of the top-farms group were located in densely populated pig areas, but
      still managed to have low usage and high technical performance; they had higher
      internal biosecurity and more extensive vaccination against respiratory
      pathogens. These results illustrate that it is possible to control infectious
      diseases using other approaches than high antimicrobial usage, even in farms with
      challenging environmental and health conditions.

PMID- 29051317
TI  - Expression and prognostic significance of ECT2 in invasive breast cancer.
AB  - AIMS: To investigate the expression of epithelial cell transforming sequence 2
      (ECT2) in invasive breast cancer and its prognostic significance. METHODS: ECT2
      immunohistochemical detection was performed in 165 breast cancer specimens and
      100 normal control tissues. Univariable and multivariable Cox proportional
      hazards regression model analysis was used to confirm independent prognostic
      factors. The PHREG procedure linear hypotheses testing method was used to analyse
      survival data. RESULTS: Expression of ECT2 in breast cancer was significantly
      higher than that of the normal control group (p<0.001), and it was related to
      tumour grade, the status of lymph node metastasis, TNM staging, recurrence
      status, menopausal status, and the Ki-67 proliferation index (p<0.05), and not
      related to age, tumour size, tumour type, expression of estrogen receptor,
      progesterone receptor and human epidermal growth factor 2, and triple-negative
      disease (p>0.05). Univariable analysis showed that expression of ECT2, the status
      of lymph node metastasis, triple-negative disease and Ki-67 proliferation index
      were related to the overall survival of patients with breast cancer (p<0.001,
      p=0.006, p=0.001, p=0.041, respectively). PHREG procedure linear hypotheses
      testing results for overall survival revealed that high expression of ECT2, lymph
      node metastasis, triple-negative disease and high Ki-67 proliferation index
      predicted lower overall survival rates. Multivariable Cox regression indicated
      that high expression of ECT2 and triple-negative disease were independent
      prognostic factors for patients with breast cancer (p<0.001, p=0.004,
      respectively). CONCLUSIONS: Expression of ECT2 may be one of the main causes of
      the occurrence and development of breast cancer, and high expression of ECT2 as
      an independent prognostic factor predicts a poor prognosis. ECT2 could also be a
      potential molecular target for designing therapeutic strategies for breast
      cancer.

PMID- 29051318
TI  - Evaluation of the Selectivity and Cysteine Dependence of Inhibitors across the
      Regulator of G Protein-Signaling Family.
AB  - Since their discovery more than 20 years ago, regulators of G protein-signaling
      (RGS) proteins have received considerable attention as potential drug targets
      because of their ability to modulate Galpha activity. Efforts to identify small
      molecules capable of inhibiting the protein-protein interactions between
      activated Galpha subunits and RGS proteins have yielded a substantial number of
      inhibitors, especially toward the well studied RGS4. These efforts also
      determined that many of these small molecules inhibit the protein-protein
      interactions through covalent modification of cysteine residues within the RGS
      domain that are located distal to the Galpha-binding interface. As some of these
      cysteine residues are highly conserved within the RGS family, many of these
      inhibitors display activity toward multiple RGS family members. In this work, we
      sought to determine the selectivity of these small-molecule inhibitors against 12
      RGS proteins, as well as against the cysteine-null mutants for 10 of these
      proteins. Using both biochemical and cell-based methods to assess Galpha-RGS
      complex formation and Galpha enzymatic activity, we found that several previously
      identified RGS4 inhibitors were active against other RGS members, such as RGS14,
      with comparable or greater potency. Additionally, for every compound tested,
      activity was dependent on the presence of cysteine residues. This work defines
      the selectivity of commercially available RGS inhibitors and provides insight
      into the RGS family members for which drug discovery efforts may be most likely
      to succeed.

PMID- 29051319
TI  - CCL26 Participates in the PRL-3-Induced Promotion of Colorectal Cancer Invasion
      by Stimulating Tumor-Associated Macrophage Infiltration.
AB  - Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages
      (TAM) influence cancer progression. Whether PRL-3 plays a critical role in
      colorectal cancer invasion and metastasis by inducing TAM infiltration remains
      unclear. In the current study, we investigated the effects of chemokine ligand 26
      (CCL26) on TAM infiltration and colorectal cancer invasion and the underlying
      mechanism in colorectal cancer cells by overexpressing or silencing PRL-3. We
      found that PRL-3 upregulated CCL26 expression correlatively and participated in
      cell migration, according to the results of gene ontology analysis. In addition,
      IHC analysis results indicated that the PRL-3 and CCL26 levels were positively
      correlated and elevated in stage III and IV colorectal cancer tissues and were
      associated with a worse prognosis in colorectal cancer patients. Furthermore, we
      demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3
      receptor. When LoVo-P and HT29-C cells were cocultured with TAMs, CCL26 binding
      to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by
      mobilizing intracellular Ca2+of TAMs to increase the expression of IL6 and IL8.
      In addition, IHC results indicated that protein levels of CCR3 and TAMs counts
      were higher in stage III and IV colorectal cancer tissues and correlated with
      CCL26. Moreover, similar results were observed in vivo using mice injected with
      LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential
      prognostic marker that promotes colorectal cancer invasion and metastasis by
      upregulating CCL26 to induce TAM infiltration. Mol Cancer Ther; 17(1); 276-89.
      (c)2017 AACR.

PMID- 29051320
TI  - Combinatorial Treatment with mTOR Inhibitors and Streptozotocin Leads to
      Synergistic In Vitro and In Vivo Antitumor Effects in Insulinoma Cells.
AB  - Streptozotocin-based chemotherapy is the first-line chemotherapy recommended for
      advanced pancreatic neuroendocrine tumors (pNETs), whereas targeted therapies,
      including mTOR inhibitors, are available in second-line treatment. Unfortunately,
      objective response rates to both treatments are limited. Because mTOR pathway
      activation, commonly observed in pNETs, has been reported as one of the major
      mechanisms accounting for chemoresistance, we investigated the potential benefit
      of mTOR inhibition combined with streptozotocin treatment in a subset of pNETs,
      namely insulinomas. To evaluate the potential of mTOR inhibition in combination
      with streptozotocin, we selected four different inhibitors acting at various
      levels of the pathway (everolimus: inhibition of mTORC1; MK-2206: inhibition of
      AKT; BKM120: inhibition of PI3K, mTORC1, and mTORC2; and BEZ235: inhibition of
      mTORC1 and mTORC2). Effects on cell viability and apoptosis were assessed in
      insulinoma cell lines INS-1E (rat) and MIN6 (mouse) in vitro and were confirmed
      in vivo by using a mouse model of hepatic tumor dissemination after intrasplenic
      xenograft. In vitro, all four combinations display synergistic effects. These
      combinations lead to heterogeneous mTOR pathway inhibition, in agreement with
      their respective target, and increased apoptosis. In vivo, tumor growth in the
      liver was significantly inhibited by combining streptozotocin with everolimus (P
      = 0.0014), BKM120 (P = 0.0092), or BEZ235 (P = 0.008) as compared to each agent
      alone. These results suggest that targeting the mTOR pathway in combination with
      streptozotocin could be of potential benefit for insulinomas and pNET patients
      and thus support further clinical investigations. Mol Cancer Ther; 17(1); 60-72.
      (c)2017 AACR.

PMID- 29051321
TI  - Liquid Biopsies Using Plasma Exosomal Nucleic Acids and Plasma Cell-Free DNA
      Compared with Clinical Outcomes of Patients with Advanced Cancers.
AB  - Purpose: Blood-based liquid biopsies offer easy access to genomic material for
      molecular diagnostics in cancer. Commonly used cell-free DNA (cfDNA) originates
      from dying cells. Exosomal nucleic acids (exoNAs) originate from living cells,
      which can better reflect underlying cancer biology.Experimental Design: Next
      generation sequencing (NGS) was used to test exoNA, and droplet digital PCR
      (ddPCR) and BEAMing PCR were used to test cfDNA for BRAFV600, KRASG12/G13, and
      EGFRexon19del/L858R mutations in 43 patients with progressing advanced cancers.
      Results were compared with clinical testing of archival tumor tissue and clinical
      outcomes.Results: Forty-one patients had BRAF, KRAS, or EGFR mutations in tumor
      tissue. These mutations were detected by NGS in 95% of plasma exoNA samples, by
      ddPCR in 92% of cfDNA samples, and by BEAMing in 97% cfDNA samples. NGS of exoNA
      did not detect any mutations not present in tumor, whereas ddPCR and BEAMing
      detected one and two such mutations, respectively. Compared with patients with
      high exoNA mutation allelic frequency (MAF), patients with low MAF had longer
      median survival (11.8 vs. 5.9 months; P = 0.006) and time to treatment failure
      (7.4 vs. 2.3 months; P = 0.009). A low amount of exoNA was associated with
      partial response and stable disease >=6 months (P = 0.006).Conclusions: NGS of
      plasma exoNA for common BRAF, KRAS, and EGFR mutations has high sensitivity
      compared with clinical testing of archival tumor and testing of plasma cfDNA. Low
      exoNA MAF is an independent prognostic factor for longer survival. Clin Cancer
      Res; 24(1); 181-8. (c)2017 AACR.

PMID- 29051324
TI  - Corneal complications after orbital radiotherapy for primary epithelial
      malignancies of the lacrimal gland.
AB  - PURPOSE: To review the long-term corneal complications after high-dose external
      beam orbital radiotherapy given to patients for lacrimal gland carcinomas. The
      impact of prophylactic measures to improve long-term ocular surface health is
      also assessed. DESIGN: Retrospective case series. PARTICIPANTS: Patients under
      the care of Moorfields Eye Hospital and receiving external beam radiotherapy for
      primary epithelial lacrimal gland carcinoma between 1975 and 2014. METHODS:
      Retrospective review of ophthalmic case notes at Moorfields Eye Hospital, and
      oncology and general physician records. MAIN OUTCOME MEASURES: The occurrence of
      corneal perforation, and time to perforation. RESULTS: Sixty-seven patients were
      included in this study, of whom nine (13%) developed corneal perforation at a
      median time of 10.4 months after radiotherapy (mean 35; range 3.2 months to 14.5
      years); the majority (7/9; 78%) perforated within 36 months of radiotherapy. The
      mean follow-up interval of the whole cohort was 8.2 years (median 4.6; range, 2
      months to 30.7 years). CONCLUSIONS: Although most patients with globe-sparing
      treatment of lacrimal gland carcinoma did not suffer corneal perforation, they
      usually require long-term therapy to maintain the ocular surface. The high-dose
      external beam radiotherapy needed for lacrimal gland carcinoma can produce
      significant ocular surface morbidity, and the 13% incidence of corneal
      perforation was greatest in the first 3 years after irradiation.

PMID- 29051322
TI  - A Multicenter Phase I Study Evaluating Dual PI3K and BRAF Inhibition with PX-866
      and Vemurafenib in Patients with Advanced BRAF V600-Mutant Solid Tumors.
AB  - Purpose: The objectives of the study were to evaluate the safety of daily oral PX
      866 in combination with twice daily vemurafenib and to identify potential
      predictive biomarkers for this novel combination.Experimental Design: We
      conducted a phase I, open-label, dose-escalation study in patients with advanced
      BRAF V600-mutant solid tumors. PX-866 was administered on a continuous schedule
      in combination with vemurafenib. Patients underwent a baseline and on-treatment
      biopsy after 1-week of PX-866 monotherapy for biomarker assessment.Results:
      Twenty-four patients were enrolled. The most common treatment-related adverse
      events were gastrointestinal side effects. One dose-limiting toxicity (DLT) of
      grade 3 rash and one DLT of grade 3 pancreatitis were observed in cohort 2 (PX
      866 6 mg daily; vemurafenib 960 mg twice daily) and cohort 3 (PX-866 8 mg daily;
      vemurafenib 960 mg twice daily), respectively. Of 23 response-evaluable patients,
      seven had confirmed partial responses (PR), 10 had stable disease, and six had
      disease progression. Decreases in intratumoral pAKT expression were observed
      following treatment with PX-866. Patients who achieved PRs had higher rates of
      PTEN loss by IHC (80% vs. 58%) and pathogenic PTEN mutations and/or deletions
      (57% vs. 25%). Two patients with durable PRs had an increase in intratumoral CD8+
      T-cell infiltration following treatment with PX-866.Conclusions: PX-866 was well
      tolerated at its maximum tolerated single-agent dose when given in combination
      with a modified dose of vemurafenib (720 mg twice daily). Response to treatment
      appeared to be associated with PTEN loss and treatment with PX-866 seemed to
      increase CD8+ T-cell infiltration in some patients. Clin Cancer Res; 24(1); 22
      32. (c)2017 AACR.

PMID- 29051323
TI  - Epithelial-to-Mesenchymal Transition Antagonizes Response to Targeted Therapies
      in Lung Cancer by Suppressing BIM.
AB  - Purpose: Epithelial-to-mesenchymal transition (EMT) confers resistance to a
      number of targeted therapies and chemotherapies. However, it has been unclear why
      EMT promotes resistance, thereby impairing progress to overcome it.Experimental
      Design: We have developed several models of EMT-mediated resistance to EGFR
      inhibitors (EGFRi) in EGFR-mutant lung cancers to evaluate a novel mechanism of
      EMT-mediated resistance.Results: We observed that mesenchymal EGFR-mutant lung
      cancers are resistant to EGFRi-induced apoptosis via insufficient expression of
      BIM, preventing cell death despite potent suppression of oncogenic signaling
      following EGFRi treatment. Mechanistically, we observed that the EMT
      transcription factor ZEB1 inhibits BIM expression by binding directly to the BIM
      promoter and repressing transcription. Derepression of BIM expression by
      depletion of ZEB1 or treatment with the BH3 mimetic ABT-263 to enhance "free"
      cellular BIM levels both led to resensitization of mesenchymal EGFR-mutant
      cancers to EGFRi. This relationship between EMT and loss of BIM is not restricted
      to EGFR-mutant lung cancers, as it was also observed in KRAS-mutant lung cancers
      and large datasets, including different cancer subtypes.Conclusions: Altogether,
      these data reveal a novel mechanistic link between EMT and resistance to lung
      cancer targeted therapies. Clin Cancer Res; 24(1); 197-208. (c)2017 AACR.

PMID- 29051325
TI  - Impact of baseline Diabetic Retinopathy Severity Scale scores on visual outcomes
      in the VIVID-DME and VISTA-DME studies.
AB  - BACKGROUND/AIMS: To evaluate intravitreal aflibercept versus laser in subgroups
      of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores <=43,
      47, and >=53 in VIVID-DME and VISTA-DME. METHODS: Patients with diabetic macular
      oedema were randomised to receive intravitreal aflibercept 2 mg every 4 weeks
      (2q4), intravitreal aflibercept 2 mg every 8 weeks after five initial monthly
      doses (2q8), or macular laser photocoagulation at baseline with sham injections
      at every visit. These post hoc analyses evaluate outcomes based on baseline DRSS
      scores in patients in the integrated dataset. The 2q4 and 2q8 treatment groups
      were also pooled. RESULTS: 748 patients had a baseline DRSS score based on fundus
      photographs (<=43, n=301; 47, n=153; >=53, n=294). At week 100, the least squares
      mean difference between treatment groups (effect of intravitreal aflibercept
      above that of laser, adjusting for baseline best-corrected visual acuity) was 8.9
      (95% CI 5.99 to 11.81), 9.7 (95% CI 5.54 to 13.91), and 11.0 (95% CI 7.96 to
      14.1) letters in those with baseline DRSS scores <=43, 47, and >=53,
      respectively. The proportions of patients with >=2 step DRSS score improvement
      were greater in the intravitreal aflibercept group versus laser, respectively,
      for those with baseline DRSS scores of <=43 (13% vs 5.9%), 47 (25.8% vs 4.5%),
      and >=53 (64.5% vs 28.4%). CONCLUSIONS: Regardless of baseline DRSS score,
      functional outcomes were superior in intravitreal aflibercept-treated patients,
      demonstrating consistent treatment benefit across various baseline levels of
      retinopathy. TRIAL REGISTRATION NUMBERS: NCT01331681 and NCT01363440, Post
      results.

PMID- 29051326
TI  - Multimodal imaging of small hard retinal drusen in young healthy adults.
AB  - BACKGROUND: Small hard macular drusen can be observed in the retina of adults as
      young as 18 years of age. Here, we seek to describe the in vivo topography and
      geometry of these drusen. METHODS: Retinal images were acquired in young, healthy
      adults using colour fundus photography, spectral domain optic coherence
      tomography (SD-OCT), reflectance flood-illuminated adaptive optic ophthalmoscopy
      (AO flood) and reflectance adaptive optic scanning light ophthalmoscopy (AOSLO)
      in both confocal and non-confocal split-detection modalities. Small bright yellow
      hard drusen within a 10 degree radius from the foveal centre were characterised.
      RESULTS: Small hard drusen were seen on colour photographs in 21 out of 97
      participants and 26 drusen in 12 eyes in 11 participants were imaged using the
      full protocol. Drusen were easily identifiable in all modalities, except a few
      very small ones, which were not visible on SD-OCT. On AOSLO images, these drusen
      appeared as round, oval or lobular areas (up to three lobules) of diameter 22-61
      um where cone photoreceptor reflectivity and density was decreased (p=0.049).
      This was usually associated with discrete thickening of the retinal pigment
      epithelium (RPE) complex. CONCLUSION: High lateral resolution imaging of small
      lobular hard retinal drusen suggests formation through the confluence of two or
      more smaller round lesions. The outline and size of these smaller lesions
      corresponds to 1-4 RPE cells. Prospective longitudinal studies are needed to
      determine the ultimate fate of small hard drusen and their potential relation to
      age-related macular degeneration.

PMID- 29051327
TI  - Asymmetrical accommodation in hyperopic anisometropic amblyopia.
AB  - BACKGROUND/AIMS: To investigate the presence of asymmetrical accommodation in
      hyperopic anisometropic amblyopia. METHODS: Accommodation in each eye and
      binocular vergence were measured simultaneously using a PlusoptiX SO4
      photorefractor in 26 children aged 4-8 years with hyperopic anisometropic
      amblyopia and 13 controls (group age-matched) while they viewed a detailed target
      moving in depth. RESULTS: Without spectacles, only 5 (19%) anisometropes
      demonstrated symmetrical accommodation (within the 95% CI of the mean gain of the
      sound eye of the anisometropic group), whereas 21 (81%) demonstrated asymmetrical
      accommodation. Of those, 15 (58%) showed aniso-accommodation and 6 (23%)
      demonstrated 'anti-accommodation' (greater accommodation for distance than for
      near). In those with anti-accommodation, the response gain in the sound eye was
      (0.93+/-0.20) while that of the amblyopic eye showed a negative accommodation
      gain of (-0.44+/-0.23). Anti-accommodation resolved with spectacles. Vergence
      gains were typical in those with symmetrical and asymmetrical accommodation.
      CONCLUSION: The majority of hyperopic anisometropic amblyopes demonstrated non
      consensual asymmetrical accommodation. Approximately one in four demonstrated
      anti-accommodation.

PMID- 29051328
TI  - How does sevoflurane induction, followed by a ketamine maintenance infusion,
      affect intraocular pressure? Establishment of an anaesthetic protocol for
      paediatric glaucoma examinations under anaesthesia.
AB  - : Accurate measurement of intraocular pressure (IOP) is essential in paediatric
      glaucoma management. Children require serial measurements and examination under
      anaesthesia (EUA). Most anaesthetic agents reduce IOP, and the ideal time to
      measure IOP under anaesthesia is questionable. STUDY PURPOSE: To determine the
      effect of sevoflurane induction, followed by intravenous ketamine infusion on
      IOP, in children undergoing EUA for glaucoma or suspected glaucoma, and to
      establish the earliest time point at which reliable, repeatable IOP measurements
      can be obtained under anaesthesia. METHOD: A prospective, descriptive study of
      IOP changes occurring in children requiring EUAs. A standardised anaesthetic
      protocol: sevoflurane induction, intravenous cannulation, 2 mg/kg intravenous
      ketamine bolus and 4 mg/kg/hour maintenance for 15 min. IOP measurements (taken
      supine with a Perkins applanation tonometer) and physiological variables were
      recorded. RESULTS: IOPs were measured in 25 children (50 eyes). Twenty-six eyes
      (52%) were glaucomatous. Mean patient age was 29 months (2-88 months).
      Physiological variables returned to baseline at 8 min, correlating with recorded
      sevoflurane elimination. Mean IOP after sevoflurane induction was 3.68 mm Hg
      lower than with ketamine maintenance at 15 min (95% CI 1.35 to 6.02 mm Hg)
      (p=0.002). Contrastingly, the difference in IOP between ketamine anaesthesia at
      15 min and near wakefulness was 0.28 mm Hg (95% CI -2.23 to 2.79 mm Hg)
      (p=0.826). CONCLUSION: Sevoflurane's IOP-lowering effect is reversed 15 min after
      the discontinuation of the inhalational gas, if anaesthesia is maintained with an
      intravenous ketamine infusion. IOP measurements appear to stabilise at this time
      point until the point of near wakefulness and may reflect awake values.

PMID- 29051329
TI  - Safety profile and efficacy of tacrolimus in the treatment of birdshot
      retinochoroiditis: a retrospective case series review.
AB  - AIM: Evaluation of the use of tacrolimus in the treatment of birdshot
      retinochoroiditis (BRC) at a tertiary referral centre with the aim to describe
      its safety and efficacy. METHODS: The medical records of 25 patients diagnosed
      with BRC at uveitis service, Moorfields Eye Hospital, and who had received
      tacrolimus treatment were retrospectively reviewed. The main outcome measures of
      the study were (1) safety of tacrolimus in terms of side effects and (2)
      efficacy, as measured both by control of inflammation and visual function
      assessed by Humphrey visual fields and electrophysiological testing over at least
      6 months and then 1 year. RESULTS: Tacrolimus was commenced in 25 patients (mean
      age 50.4+/-10.8 years) and was well tolerated in 21 patients (84%). It was
      necessary to stop the tacrolimus in four patients. No patient showed major
      changes in renal function: 3/21 patients (14.28%) showed slightly abnormal (less
      than 30%) function at the end of the first month of treatment; 1/21 (4.76%)
      patients at 3 months, but at the end of a 6-month treatment period only 1/21
      patients (4.76%) showed minor abnormality in renal function. The mean daily
      prednisolone dose was 19.7 mg at the beginning of the study, which had fallen to
      6.9 mg at the end (t=5.071, p=0.001). Visual acuity mostly remained stable.
      Visual fields improved over time (mean improvement in Humphrey mean deviation,
      right eye=1.8+/-2.4 dB, t=3.821, p=0.004; left eye=1.9+/-2.7, dB, t=3.06,
      p=0.007). Electrophysiological function showed improvement in 10 patients, and in
      four patients an initial deterioration in function improved following tacrolimus
      dose adjustment. CONCLUSION: Tacrolimus has a good safety profile for long-term
      use in patients with BRC as a second-line agent enabling steroid sparing and
      visual function stabilisation or improvement.

PMID- 29051330
TI  - Cross-Cultural Differences in Communication About a Dying Child.
AB  - There are more migrants, refugees, and immigrants adrift in the world today than
      at any time in the recent past. Doctors and hospitals must care for people from
      many different cultures, countries, and religious backgrounds. We sometimes find
      our own deeply held beliefs and values challenged. In this "Ethics Rounds," we
      present a case in which a Pakistani immigrant family faces a tragic medical
      situation and wants to deal with it in ways that might be normative in their own
      culture but are aberrant in ours. We asked the American doctors and 2 Pakistani
      health professionals to think through the issues. We also invited the father to
      talk about his own experience and preferences. We conclude that strict adherence
      to Western ethical norms may not always be the best choice. Instead, an approach
      based on cultural humility may often allow people on both sides of a cultural
      divide to learn from one another.

PMID- 29051331
TI  - Intravenous Zanamivir in Hospitalized Patients With Influenza.
AB  - BACKGROUND: Children with severe influenza infection may require parenteral
      therapy if oral or inhaled therapies are ineffective or cannot be administered.
      Results from a study investigating intravenous (IV) zanamivir for the treatment
      of hospitalized infants and children with influenza are presented. METHODS: This
      phase II, open-label, multicenter, single-arm study assessed the safety of
      investigational IV zanamivir in hospitalized children with influenza. Safety
      outcomes included treatment-emergent adverse events (TEAEs), clinical laboratory
      measurements, and vital signs. Clinical outcomes, pharmacokinetics, and virologic
      efficacy data were collected as key secondary outcomes. RESULTS: In total, 71
      children received treatment with investigational IV zanamivir (exposure
      comparable to 600 mg twice daily in adults). TEAEs and serious TEAEs (STEAEs)
      were reported in 51 (72%) and 15 (21%) patients, respectively. The mortality rate
      was 7%, and median durations of hospital and ICU stays were 6 and 7.5 days,
      respectively. No STEAEs or deaths were considered related to IV zanamivir
      treatment, and no patterns of TEAEs, laboratory abnormalities, or vital signs
      were observed. The mean zanamivir exposures from 34 patients with normal renal
      function who received 12 mg/kg, 14 mg/kg, or 600 mg of IV zanamivir ranged from
      64.5 to 110 hour.ug/mL. The median change from baseline in the viral load was 
      1.81 log10 copies per mL after 2 days of treatment. CONCLUSIONS: The safety
      profile of IV zanamivir was favorable, with no drug-related STEAEs reported. The
      majority of children experienced virologic response and clinical improvement
      during the treatment course. Systemic zanamivir exposures in children were
      consistent with adults.

PMID- 29051332
TI  - Parenchymal strain heterogeneity during oscillatory ventilation: why two
      frequencies are better than one.
AB  - High-frequency oscillatory ventilation (HFOV) relies on low tidal volumes cycled
      at supraphysiological rates, producing fundamentally different mechanisms for gas
      transport and exchange compared with conventional mechanical ventilation. Despite
      the appeal of using low tidal volumes to mitigate the risks of ventilator-induced
      lung injury, HFOV has not improved mortality for most clinical indications. This
      may be due to nonuniform and frequency-dependent distribution of flow throughout
      the lung. The goal of this study was to compare parenchymal strain heterogeneity
      during eucapnic HFOV when using oscillatory waveforms that consisted of either a
      single discrete frequency or two simultaneous frequencies. We utilized a three
      dimensional, anatomically structured canine lung model for simulating frequency
      dependent ventilation distribution. Gas transport was simulated via direct
      alveolar ventilation, advective mixing at bifurcations, turbulent and oscillatory
      dispersion, and molecular diffusion. Volume amplitudes at each oscillatory
      frequency were iteratively optimized to attain eucapnia. Ventilation using single
      frequency HFOV demonstrated increasing heterogeneity of acinar flow and CO2
      elimination with frequency for frequencies greater than the resonant frequency.
      For certain pairs of frequencies, a linear combination of the two corresponding
      ventilation distributions yielded reduced acinar strain heterogeneity compared
      with either frequency alone. Our model demonstrates that superposition of two
      simultaneous oscillatory frequencies can achieve more uniform ventilation
      distribution, and therefore lessen the potential for ventilator-induced lung
      injury, compared with traditional single-frequency HFOV. NEW & NOTEWORTHY In this
      study, we simulated oscillatory ventilation with multiple simultaneous
      frequencies using a computational lung model that includes distributed flow and
      gas transport. A mechanism of benefit was identified by which ventilation with
      two simultaneous frequencies results in reduced acinar strain heterogeneity
      compared with either frequency alone. This finding suggests the possibility of
      tuning the spectral content of ventilator waveforms according to patient-specific
      mechanical heterogeneity.

PMID- 29051333
TI  - Preload-corrected dynamic Starling mechanism in patients with heart failure with
      preserved ejection fraction.
AB  - : The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of
      stroke volume (SV) because of breath-by-breath changes in left-ventricular end
      diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose
      of this study was to test whether the LVEDP-SV relationship remained impaired in
      heart failure with preserved ejection fraction (HFpEF) patients after
      normalization of LVEDP. Right heart catheterization and model-flow analysis of
      the arterial pressure waveform were performed while preload was manipulated using
      lower-body negative pressure to alter LVEDP. The DSM was compared at similar
      levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls
      ( n = 12) (HFpEF vs. CONTROLS: 10.9 +/- 3.8 vs. 11.2 +/- 1.3 mmHg, P = 1.00).
      Transfer function analysis between diastolic pulmonary artery pressure (PAD)
      representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and
      coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than
      in the controls, even at a similar level of LVEDP (0.46 +/- 0.19 vs. 0.99 +/-
      0.39 ml.m-2.mmHg-1, P = 0.0018). Moreover, the power spectral density of PAD, the
      input variability, was greater in the HFpEF group than the controls (0.75 +/-
      0.38 vs. 0.28 +/- 0.26 mmHg2, P = 0.01). Conversely, the power spectral density
      of SV index, the output variability, was not different between the groups ( P =
      0.97). There was no difference in the coherence, which confirms the reliability
      of the linear transfer function between the two groups (0.71 +/- 0.13 vs. 0.77 +/
      0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age
      matched controls even at a similar level of LVEDP, which may reflect intrinsic LV
      diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW &
      NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic
      modulation of stroke volume because of breath-by-breath changes in left
      ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial
      coupling. Although the DSM gain is impaired in heart failure with preserved
      ejection fraction (HFpEF) patients, it is not clear whether this is because of
      higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF
      patients is severely impaired, even at a similar level of LVEDP, which may
      reflect intrinsic left-ventricular diastolic dysfunction.

PMID- 29051334
TI  - The biomechanics of the fastest sprinter with a unilateral transtibial
      amputation.
AB  - People have debated whether athletes with transtibial amputations should compete
      with nonamputees in track events despite insufficient information regarding how
      the use of running-specific prostheses (RSPs) affect athletic performance. Thus,
      we sought to quantify the spatiotemporal variables, ground reaction forces, and
      spring-mass mechanics of the fastest athlete with a unilateral transtibial
      amputation using an RSP to reveal how he adapts his biomechanics to achieve elite
      running speeds. Accordingly, we measured ground reaction forces during treadmill
      running trials spanning 2.87 to 11.55 m/s of the current male International
      Paralympic Committee T44 100- and 200-m world record holder. To achieve faster
      running speeds, the present study's athlete increased his affected leg (AL) step
      lengths ( P < 0.001) through longer contact lengths ( P < 0.001) and his
      unaffected leg (UL) step lengths ( P < 0.001) through longer contact lengths ( P
      < 0.001) and greater stance average vertical ground reaction forces ( P < 0.001).
      At faster running speeds, step time decreased for both legs ( P < 0.001) through
      shorter ground contact and aerial times ( P < 0.001). Unlike athletes with
      unilateral transtibial amputations, this athlete maintained constant AL and UL
      stiffness across running speeds ( P >= 0.569). Across speeds, AL step lengths
      were 8% longer ( P < 0.001) despite 16% lower AL stance average vertical ground
      reaction forces compared with the UL ( P < 0.001). The present study's athlete
      exhibited biomechanics that differed from those of athletes with bilateral and
      without transtibial amputations. Overall, we present the biomechanics of the
      fastest athlete with a unilateral transtibial amputation, providing insight into
      the functional abilities of athletes with transtibial amputations using running
      specific prostheses. NEW & NOTEWORTHY The present study's athlete achieved the
      fastest treadmill running trial ever attained by an individual with a leg
      amputation (11.55 m/s). From 2.87 to 11.55 m/s, the present study's athlete
      maintained constant affected and unaffected leg stiffness, which is atypical for
      athletes with unilateral transtibial amputations. Furthermore, the asymmetric
      vertical ground reaction forces of athletes with unilateral transtibial
      amputations during running may be the result of leg length discrepancies.

PMID- 29051335
TI  - Coronary capillary blood flow in a rat model of congestive heart failure.
AB  - : The aim of this study was to explore the role of abnormal coronary
      microvasculature morphology and hemodynamics in the development of congestive
      heart failure (CHF). CHF was induced in rats by aortic banding, followed by
      ischemia-reperfusion and later aortic debanding. Polymerized casts of coronary
      vasculature were imaged under a scanning electron microscope (SEM). Matrix
      Laboratory (MATLAB) software was used to calculate capillary structure index
      (CSI), a measure of structural alignment also called mean vector length (MVL),
      for 93 SEM images of coronary capillaries (CSI->1 perfect linearity; CSI->0
      circular disarray). CSI was incorporated as a constant to represent tortuosity
      and nonlaminar flow in Poiseuille's equation to estimate the differences in
      capillary blood flow rate, velocity, and resistance for CHF vs. CONTROL: The
      morphology of CHF capillaries is significantly disordered and tortuous compared
      with control (CSI: 0.35 +/- 0.02 for 61 images from 7 CHF rats; 0.58 +/- 0.02 for
      32 images from 7 control rats; P < 0.01). Estimated capillary resistance in CHF
      is elevated by 173% relative to control, while blood flow rate and blood velocity
      are 56 and 43% slower than control. Capillary resistance increased 67% due to the
      significantly narrower capillary diameter in CHF, while it increased an
      additional 105% due to tortuosity. The significant structural abnormalities of
      CHF coronary capillaries may drastically stagnate hemodynamics in myocardium and
      increase resistance to blood flow. This could play a role in the development of
      CHF. NEW & NOTEWORTHY In the present study, coronary capillary tortuosity was
      measured by applying Matrix Laboratory software to scanning electron microscope
      images of capillaries in a rat model of congestive heart failure. Stagnant blood
      flow in coronary capillaries may play a role in the development of congestive
      heart failure. The application of computer modeling to histological and
      physiological data to characterize the hemodynamics of coronary microcirculation
      is a new area of study.

PMID- 29051337
TI  - Gravity outweighs the contribution of structure to passive ventilation-perfusion
      matching in the supine adult human lung.
AB  - Gravity and matched airway/vascular tree geometries are both hypothesized to be
      key contributors to ventilation-perfusion (V/Q) matching in the lung, but their
      relative contributions are challenging to quantify experimentally. We used a
      structure-based model to conduct an analysis of the relative contributions of
      tissue deformation (the "Slinky" effect), other gravitational mechanisms (weight
      of blood and gravitational gradient in tissue elastic recoil), and matched airway
      and arterial tree geometry to V/Q matching and therefore to total lung oxygen
      exchange. Our results showed that the heterogeneity in V and Q were lowest and
      the correlation between V and Q was highest when the only mechanism for V/Q
      matching was either tissue deformation or matched geometry. Heterogeneity in V
      and Q was highest and their correlation was poorest when all mechanisms were
      active (that is, at baseline). Eliminating the contribution of matched geometry
      did not change the correlation between V and Q at baseline. Despite the much
      larger heterogeneities in V and Q at baseline, the contribution of in-common (to
      V and Q) gravitational mechanisms provided sufficient compensatory V/Q matching
      to minimize the impact on oxygen transfer. In summary, this model predicts that
      during supine normal breathing under gravitational loading, passive V/Q matching
      is predominantly determined by shared gravitationally induced tissue deformation,
      compliance distribution, and the effect of the hydrostatic pressure gradient on
      vessel and capillary size and blood pressures. Contribution from the matching
      airway and arterial tree geometries in this model is minor under normal gravity
      in the supine adult human lung. NEW & NOTEWORTHY We use a computational model to
      systematically analyze contributors to ventilation-perfusion matching in the
      lung. The model predicts that the multiple effects of gravity are the predominant
      mechanism in providing passive ventilation-perfusion matching in the supine adult
      human lung under normal gravitational loads, while geometric matching of airway
      and arterial trees plays a minor role.

PMID- 29051338
TI  - Occurrence of cardiac output decrease (via stroke volume) is more pronounced in
      women than in men during prolonged dry static apnea.
AB  - Little is known about sex differences in autonomic cardiovascular regulation of
      the diving response, and the few available studies of these differences were
      conducted on subjects with limited or no diving experience. We examined the
      influence of sex on hemodynamics during dry static apnea (SA) in eight male and
      eight female elite divers matched for their breath hold (BH) ability.
      Hemodynamics was assessed by means of simultaneous echocardiography and impedance
      cardiography measurements, and arterial pressure and oxygen saturation ([Formula:
      see text]) were also collected. In the first quarter (AP25%) and half (AP50%) of
      apnea duration cardiac output (CO) showed a more rapid and intense decrease in
      women than in men (-43% vs. -17% during AP25% and -40% vs. -19% during AP50%,
      respectively, P < 0.05). At the same time points, systemic vascular resistance
      (SVR) increased more in women than in men (+22% vs. +100% at AP25% and +48% vs.
      +107% at AP50%, respectively, P < 0.05). [Formula: see text] progressively
      declined in both groups, but men showed a more pronounced decrease than women at
      the end of apneas (-13% vs. -5%, respectively, P < 0.05). In men the higher the
      body surface area values the longer the apnea, while in women the higher the SVR
      response the longer the apnea. In elite female divers, the magnitude of CO
      decrease during dry SA was larger than in male divers. The capacities to store
      oxygen and to reduce O2 consumption play a pivotal role in BH performance, but
      their extent seems to be different in the sexes. NEW & NOTEWORTHY This is the
      first study in which the influence of sex on hemodynamics during dry static apnea
      has been investigated in two groups of elite divers matched for their breath hold
      ability. We also show the correlation between the performances obtained by divers
      during a real competition and their anthropometric, respiratory, and
      cardiovascular characteristics.

PMID- 29051339
TI  - Most cost effective treatments for lung disease identified.

PMID- 29051336
TI  - Exercise limitations in heart failure with reduced and preserved ejection
      fraction.
AB  - The hallmark symptom of chronic heart failure (HF) is severe exercise
      intolerance. Impaired perfusive and diffusive O2 transport are two of the major
      determinants of reduced physical capacity and lowered maximal O2 uptake in
      patients with HF. It has now become evident that this syndrome manifests at least
      two different phenotypic variations: heart failure with preserved or reduced
      ejection fraction (HFpEF and HFrEF, respectively). Unlike HFrEF, however, there
      is currently limited understanding of HFpEF pathophysiology, leading to a lack of
      effective pharmacological treatments for this subpopulation. This brief review
      focuses on the disturbances within the O2 transport pathway resulting in limited
      exercise capacity in both HFpEF and HFrEF. Evidence from human and animal
      research reveals HF-induced impairments in both perfusive and diffusive O2
      conductances identifying potential targets for clinical intervention.
      Specifically, utilization of different experimental approaches in humans (e.g.,
      small vs. large muscle mass exercise) and animals (e.g., intravital microscopy
      and phosphorescence quenching) has provided important clues to elucidating these
      pathophysiological mechanisms. Adaptations within the skeletal muscle O2 delivery
      utilization system following established and emerging therapies (e.g., exercise
      training and inorganic nitrate supplementation, respectively) are discussed.
      Resolution of the underlying mechanisms of skeletal muscle dysfunction and
      exercise intolerance is essential for the development and refinement of the most
      effective treatments for patients with HF.

PMID- 29051340
TI  - Attenuation of Myeloid-Specific TGFbeta Signaling Induces Inflammatory
      Cerebrovascular Disease and Stroke.
AB  - RATIONALE: Cryptogenic strokes, those of unknown cause, have been estimated as
      high as 30% to 40% of strokes. Inflammation has been suggested as a critical
      etiologic factor. However, there is lack of experimental evidence. OBJECTIVE: In
      this study, we investigated inflammation-associated stroke using a mouse model
      that developed spontaneous stroke because of myeloid deficiency of TGF-beta
      (transforming growth factor-beta) signaling. METHODS AND RESULTS: We report that
      mice with deletion of Tgfbr2 in myeloid cells (Tgfbr2Myeko) developed
      cerebrovascular inflammation in the absence of significant pathology in other
      tissues, culminating in stroke and severe neurological deficits with 100%
      penetrance. The stroke phenotype can be transferred to syngeneic wild-type mice
      via Tgfbr2Myeko bone marrow transplant and can be rescued in Tgfbr2Myeko mice
      with wild-type bone marrow. The underlying mechanisms involved an increased type
      1 inflammation and cerebral endotheliopathy, characterized by elevated NF-kappaB
      (nuclear factor-kappaB) activation and TNF (tumor necrosis factor) production by
      myeloid cells. A high-fat diet accelerated stroke incidence. Anti-TNF treatment,
      as well as metformin and methotrexate, which are associated with decreased stroke
      risk in population studies, delayed stroke occurrence. CONCLUSIONS: Our studies
      show that TGF-beta signaling in myeloid cells is required for maintenance of
      vascular health and provide insight into inflammation-mediated cerebrovascular
      disease and stroke.

PMID- 29051342
TI  - 68Ga-NOTA-Functionalized Ubiquicidin: Cytotoxicity, Biodistribution, Radiation
      Dosimetry, and First-in-Human PET/CT Imaging of Infections.
AB  - Ubiquicidin is an antimicrobial peptide with great potential for nuclear imaging
      of infectious diseases, as its cationic-rich fragment TGRAKRRMQYNRR (UBI) has
      been functionalized with NOTA to allow complexation to 68Ga (68Ga-NOTA-UBI). We
      herein assess the cytotoxicity and radiation dosimetry for 68Ga-NOTA-UBI and a
      first-in-human evaluation to diagnose infectious processes. Methods: Cytotoxicity
      was evaluated in green monkey kidney epithelial (Vero) cells and MT-4 leukocytes.
      Tracer susceptibility was studied in vitro using different bacterial and fungal
      strains. PET/CT-based biodistribution, pharmacokinetics, and radiation dosimetry
      were performed on nonhuman primates. Two healthy volunteers and 3 patients with
      suspected infection underwent 68Ga-NOTA-UBI PET/CT imaging. Results: Negligible
      cytotoxicity was determined for NOTA-UBI. 68Ga-NOTA-UBI showed moderate blood
      clearance (29-min half-life) and predominant renal clearance in nonhuman
      primates. Human radiation dose estimates indicated the bladder wall as the dose
      critical tissue (185 MUSv/MBq), followed by the kidneys (23 MUSv/MBq). The total
      absorbed body dose was low (<7 MUSv/MBq); the effective dose was estimated at 17
      MUSv/MBq. 68Ga-NOTA-UBI could diagnose bone- and soft-tissue infection in 3 of 3
      patients. Conclusion:68Ga-NOTA-UBI is considered a nontoxic, safe-to-administer
      radiopharmaceutical unlikely to cause adverse effects in humans. The favorable
      tracer biodistribution and the first-in-human results will make 68Ga-NOTA-UBI
      PET/CT an encouraging future diagnostic technique with auxiliary clinical
      relevance.

PMID- 29051341
TI  - Indoor Tanning Dependence in Young Adult Women.
AB  - Background: There is mounting evidence that young people can develop a dependence
      on indoor tanning, but research on factors associated with indoor tanning
      dependence remains limited.Methods: This cross-sectional study investigated
      factors associated with indoor tanning dependence in a community sample of 389
      non-Hispanic white young adult women ages 18 to 30 who had indoor tanned >=1 time
      in the past year. Participants completed measures of indoor tanning dependence,
      including the modified CAGE and modified Diagnostic and Statistical Manual for
      Mental Disorders-IV psychiatric screening assessments, indoor tanning behavior
      and beliefs, and behavioral and psychiatric comorbidity.Results: Overall, 22.6%
      of the sample screened positive for indoor tanning dependence. In multivariable
      analyses, indoor tanning dependence was associated with younger age of indoor
      tanning initiation [adjusted odds ratio (aOR) = 0.79; P = 0.017], indoor tanning
      >=20 times in the past year (aOR = 3.03; P = 0.015), stronger beliefs about the
      benefits of tanning (aOR = 2.15; P = 0.004), greater perceived susceptibility to
      indoor tanning risks (aOR = 2.72; P < 0.001), stronger beliefs about physical
      appearance (aOR = 1.73; P = 0.037), and depressive symptoms (aOR = 3.79; P <
      0.001).Conclusions: Indoor tanning dependence among young, non-Hispanic white
      women is associated with behaviors that increase the risk of skin cancer, beliefs
      favoring the perceived benefits of tanning, and comorbid risks such as stronger
      beliefs about physical appearance and depressed mood.Impact: Comprehensive skin
      cancer prevention efforts should address indoor tanning dependence among young
      women and its leading risk factors. Cancer Epidemiol Biomarkers Prev; 26(11);
      1636-43. (c)2017 AACR.

PMID- 29051343
TI  - Iodinated Contrast Agents Perturb Iodide Uptake by the Thyroid Independently of
      Free Iodide.
AB  - Perturbation of thyroid iodide uptake is a well-documented side effect of the use
      of iodinated contrast media (ICM) administered intravenously. This side effect is
      thought to be mediated by free iodide in ICM formulations, but this hypothesis
      has never been formally proven. The aim of the present study was to assess the
      validity of this hypothesis. Methods: We used mass spectrometry analysis to
      quantify free-iodide contamination in ICM. Established cell lines expressing the
      Na/I symporter (NIS) were used to quantify the effect of ICM on iodide uptake.
      SPECT/CT was used to measure the in vivo uptake of 99mTc-pertechnetate and 123I
      in 2 NIS-expressing mouse tissues, thyroid and salivary glands. Scintiscans of
      ICM-naive and ICM-administered patients were compared. Immunohistologic and
      Western blot analyses were performed to evaluate NIS protein expression in these
      organs. Results: Although free iodide was present in ICM formulations, in vitro
      uptake of iodide by NIS-expressing cells was not significantly affected by ICM.
      In mice, intravenous or sublingual administration of ICM led to a reduction in
      radiotracer uptake by the thyroid, accompanied by a dramatic reduction in NIS
      protein expression in this tissue. In the salivary glands, neither radiotracer
      uptake nor NIS protein expression was affected by ICM. The thyroid-selective
      effect of ICM was also observed in humans. Administration of potassium iodide as
      a source of free iodide led to a diminution of 99mTc-pertechnetate uptake in both
      mouse thyroid and mouse salivary glands. Altogether, these data rule out a direct
      intervention of free iodide in the perturbation of thyroid uptake and suggest a
      direct and selective effect of ICM on the thyroid. Conclusion: We demonstrated
      that ICM reduce thyroid uptake of iodide independently of free iodide. This
      effect is due to a specific and dramatic decrease in NIS expression in
      thyrocytes. These data cast serious doubt on the relevance of measuring urinary
      iodide concentration to evaluate the delay between ICM administration and
      radioiodine therapy in patients with differentiated thyroid carcinoma. Finally,
      the ability of ICM to perturb iodide uptake in the thyroid may be used in
      radioprotection.

PMID- 29051344
TI  - Nuclear Medicine Training in Europe: "All for One, One for All".

PMID- 29051345
TI  - Reply: Using and Interpreting 18F-FDG PET/CT Images in Patients Referred for
      Assessment of Cardiac Sarcoidosis: The Devil Is in the Details.

PMID- 29051346
TI  - Data-Driven Prioritization and Review of Targets for Molecular-Based Theranostic
      Approaches in Pancreatic Cancer.
AB  - Molecularly targeted therapeutic and imaging strategies directed at aberrant
      signaling pathways in pancreatic tumor cells may improve the poor outcome of
      pancreatic ductal adenocarcinoma (PDA). Therefore, relevant molecular targets
      need to be identified. Methods: We collected publicly available expression
      profiles of patient-derived normal pancreatic tissue (n = 77) and PDA samples (n
      = 103). Functional genomic messenger RNA profiling was applied to predict target
      upregulation on the protein level. We prioritized these targets based on current
      status of preclinical therapeutic and imaging evaluation in PDA. Results: We
      identified 213 significantly upregulated proteins in PDA compared with normal
      pancreatic tissue. We prioritized mucin-1, mesothelin, gamma-glutamyltransferase
      5, and cathepsin-E as the most interesting targets, because studies already
      demonstrated their potential for both therapeutic and imaging strategies in
      literature. Conclusion: This study can assist clinicians and drug developers in
      deciding which theranostic targets should be taken for further clinical
      evaluation in PDA.

PMID- 29051347
TI  - BP Measurement in Clinical Practice: Time to SPRINT to Guideline-Recommended
      Protocols.
AB  - Hypertension is the leading chronic disease risk factor in the world and is
      especially important in patients with CKD, nearly 90% of whom have hypertension.
      Recently, in the Systolic BP Intervention Trial (SPRINT), intensive lowering of
      clinic systolic BP to a target <120 mm Hg, compared with a standard BP target of
      <140 mm Hg, reduced risk for cardiovascular disease and all-cause mortality.
      However, because BP was measured unobserved using an automated device, some
      investigators have questioned the ability to translate SPRINT results into
      routine clinical practice, in which measurement of BP is typically less
      standardized. In this review, we discuss the BP measurement techniques used in
      major observational studies and clinical trials that form the evidence base for
      our current approach to treating hypertension, evaluate the effect of measurement
      technique on BP readings, and explore how ambulatory BP data from the SPRINT
      trial may inform this discussion. We conclude by arguing for implementation of
      guideline-recommended BP measurement techniques in routine clinical practice.

PMID- 29051348
TI  - Ultraslow waves on the nanoscale.
AB  - There has recently been a surge of interest in the physics and applications of
      broadband ultraslow waves in nanoscale structures operating below the diffraction
      limit. They range from light waves or surface plasmons in nanoplasmonic devices
      to sound waves in acoustic-metamaterial waveguides, as well as fermions and
      phonon polaritons in graphene and van der Waals crystals and heterostructures. We
      review the underlying physics of these structures, which upend traditional wave
      slowing approaches based on resonances or on periodic configurations above the
      diffraction limit. Light can now be tightly focused on the nanoscale at
      intensities up to ~1000 times larger than the output of incumbent near-field
      scanning optical microscopes, while exhibiting greatly boosted density of states
      and strong wave-matter interactions. We elucidate the general methodology by
      which broadband and, simultaneously, large wave decelerations, well below the
      diffraction limit, can be obtained in the above interdisciplinary fields. We also
      highlight a range of applications for renewable energy, biosensing, quantum
      optics, high-density magnetic data storage, and nanoscale chemical mapping.

PMID- 29051349
TI  - Comment on "Persistent effects of pre-Columbian plant domestication on Amazonian
      forest composition".
AB  - Levis et al (Research Articles, 3 March 2017, p. 925) concluded that pre
      Columbian tree domestication has shaped present-day Amazonian forest composition.
      The study, however, downplays five centuries of human influence following
      European arrival to the Americas. We show that the effects of post-Columbian
      activities in Amazonia are likely to have played a larger role than pre-Columbian
      ones in shaping the observed floristic patterns.

PMID- 29051350
TI  - Response to Comment on "Persistent effects of pre-Columbian plant domestication
      on Amazonian forest composition".
AB  - McMichael et al state that we overlooked the effects of post-Columbian human
      activities in shaping current floristic patterns in Amazonian forests. We
      formally show that post-Columbian human influences on Amazonian forests are
      indeed important, but they have played a smaller role when compared to the
      persistent effects of pre-Columbian human activities on current forest
      composition.

PMID- 29051353
TI  - A spacetime tremor and a celestial light show.

PMID- 29051351
TI  - Brexit and European science.

PMID- 29051354
TI  - Analysis of China's one-child policy sparks uproar.

PMID- 29051355
TI  - Trump team raises price tag for 2020 census.

PMID- 29051356
TI  - Emails reveal pressures on NIH gun research.

PMID- 29051357
TI  - Storms await weather executive at climate agency.

PMID- 29051358
TI  - Untangling spider biology.

PMID- 29051359
TI  - A spinner's secrets.

PMID- 29051360
TI  - Silken promises.

PMID- 29051361
TI  - Original sin.

PMID- 29051362
TI  - Digital nature: Are field trips a thing of the past?

PMID- 29051363
TI  - Flicking the switch on a molecular gate.

PMID- 29051364
TI  - Converting MOFs into amination catalysts.

PMID- 29051365
TI  - Nerves switch on angiogenic metabolism.

PMID- 29051367
TI  - Intestinal inflammation induced by oral bacteria.

PMID- 29051366
TI  - A biochemical sulfur delivery service.

PMID- 29051368
TI  - Deep risks from offshore development.

PMID- 29051369
TI  - Culturally inclusive STEM education.

PMID- 29051370
TI  - Incentives for Galapagos protection.

PMID- 29051372
TI  - A liquid metal reaction environment for the room-temperature synthesis of
      atomically thin metal oxides.
AB  - Two-dimensional (2D) oxides have a wide variety of applications in electronics
      and other technologies. However, many oxides are not easy to synthesize as 2D
      materials through conventional methods. We used nontoxic eutectic gallium-based
      alloys as a reaction solvent and co-alloyed desired metals into the melt. On the
      basis of thermodynamic considerations, we predicted the composition of the self
      limiting interfacial oxide. We isolated the surface oxide as a 2D layer, either
      on substrates or in suspension. This enabled us to produce extremely thin
      subnanometer layers of HfO2, Al2O3, and Gd2O3 The liquid metal-based reaction
      route can be used to create 2D materials that were previously inaccessible with
      preexisting methods. The work introduces room-temperature liquid metals as a
      reaction environment for the synthesis of oxide nanomaterials with low
      dimensionality.

PMID- 29051371
TI  - Adrenergic nerves activate an angio-metabolic switch in prostate cancer.
AB  - Nerves closely associate with blood vessels and help to pattern the vasculature
      during development. Recent work suggests that newly formed nerve fibers may
      regulate the tumor microenvironment, but their exact functions are unclear.
      Studying mouse models of prostate cancer, we show that endothelial beta
      adrenergic receptor signaling via adrenergic nerve-derived noradrenaline in the
      prostate stroma is critical for activation of an angiogenic switch that fuels
      exponential tumor growth. Mechanistically, this occurs through alteration of
      endothelial cell metabolism. Endothelial cells typically rely on aerobic
      glycolysis for angiogenesis. We found that the loss of endothelial Adrb2, the
      gene encoding the beta2-adrenergic receptor, leads to inhibition of angiogenesis
      through enhancement of endothelial oxidative phosphorylation. Codeletion of Adrb2
      and Cox10, a gene encoding a cytochrome IV oxidase assembly factor, prevented the
      metabolic shift induced by Adrb2 deletion and rescued prostate cancer
      progression. This cross-talk between nerves and endothelial metabolism could
      potentially be targeted as an anticancer therapy.

PMID- 29051373
TI  - Encoding of vinylidene isomerization in its anion photoelectron spectrum.
AB  - Vinylidene-acetylene isomerization is the prototypical example of a 1,2-hydrogen
      shift, one of the most important classes of isomerization reactions in organic
      chemistry. This reaction was investigated with quantum state specificity by high
      resolution photoelectron spectroscopy of the vinylidene anions H2CC- and D2CC-
      and quantum dynamics calculations. Peaks in the photoelectron spectra are
      considerably narrower than in previous work and reveal subtleties in the
      isomerization dynamics of neutral vinylidene, as well as vibronic coupling with
      an excited state of vinylidene. Comparison with theory permits assignment of most
      spectral features to eigenstates dominated by vinylidene character. However,
      excitation of the nu6 in-plane rocking mode in H2CC results in appreciable
      tunneling-facilitated mixing with highly vibrationally excited states of
      acetylene, leading to broadening and/or spectral fine structure that is largely
      suppressed for analogous vibrational levels of D2CC.

PMID- 29051374
TI  - Rotary and linear molecular motors driven by pulses of a chemical fuel.
AB  - Many biomolecular motors catalyze the hydrolysis of chemical fuels, such as
      adenosine triphosphate, and use the energy released to direct motion through
      information ratchet mechanisms. Here we describe chemically-driven artificial
      rotary and linear molecular motors that operate through a fundamentally different
      type of mechanism. The directional rotation of [2]- and [3]catenane rotary
      molecular motors and the transport of substrates away from equilibrium by a
      linear molecular pump are induced by acid-base oscillations. The changes
      simultaneously switch the binding site affinities and the labilities of barriers
      on the track, creating an energy ratchet. The linear and rotary molecular motors
      are driven by aliquots of a chemical fuel, trichloroacetic acid. A single fuel
      pulse generates 360 degrees  unidirectional rotation of up to 87% of crown ethers
      in a [2]catenane rotary motor.

PMID- 29051375
TI  - Chaos-assisted broadband momentum transformation in optical microresonators.
AB  - The law of momentum conservation rules out many desired processes in optical
      microresonators. We report broadband momentum transformations of light in
      asymmetric whispering gallery microresonators. Assisted by chaotic motions,
      broadband light can travel between optical modes with different angular momenta
      within a few picoseconds. Efficient coupling from visible to near-infrared bands
      is demonstrated between a nanowaveguide and whispering gallery modes with quality
      factors exceeding 10 million. The broadband momentum transformation enhances the
      device conversion efficiency of the third-harmonic generation by greater than
      three orders of magnitude over the conventional evanescent-wave coupling. The
      observed broadband and fast momentum transformation could promote applications
      such as multicolor lasers, broadband memories, and multiwavelength optical
      networks.

PMID- 29051376
TI  - Defibrillation of soft porous metal-organic frameworks with electric fields.
AB  - Gas transport through metal-organic framework membranes (MOFs) was switched in
      situ by applying an external electric field (E-field). The switching of gas
      permeation upon E-field polarization could be explained by the structural
      transformation of the zeolitic imidazolate framework ZIF-8 into polymorphs with
      more rigid lattices. Permeation measurements under a direct-current E-field
      poling of 500 volts per millimeter showed reversibly controlled switching of the
      ZIF-8 into polar polymorphs, which was confirmed by x-ray diffraction and ab
      initio calculations. The stiffening of the lattice causes a reduction in gas
      transport through the membrane and sharpens the molecular sieving capability.
      Dielectric spectroscopy, polarization, and deuterium nuclear magnetic resonance
      studies revealed low-frequency resonances of ZIF-8 that we attribute to lattice
      flexibility and linker movement. Upon E-field polarization, we observed a
      defibrillation of the different lattice motions.

PMID- 29051377
TI  - Single polymer growth dynamics.
AB  - In chain-growth polymerization, a chain grows continually to reach thousands of
      subunits. However, the real-time dynamics of chain growth remains unknown. Using
      magnetic tweezers, we visualized real-time polymer growth at the single-polymer
      level. Focusing on ring-opening metathesis polymerization, we found that the
      extension of a growing polymer under a pulling force does not increase
      continuously but exhibits wait-and-jump steps. These steps are attributable to
      the formation and unraveling of conformational entanglements from newly
      incorporated monomers, whose key features can be recapitulated with molecular
      dynamics simulations. The configurations of these entanglements appear to play a
      key role in determining the polymerization rates and the dispersion among
      individual polymers.

PMID- 29051378
TI  - Quantum control of molecular collisions at 1 kelvin.
AB  - Measurement of vector correlations in molecular scattering is an indispensable
      tool for mapping out interaction potentials. In a coexpanded supersonic beam, we
      have studied the rotationally inelastic process wherein deuterium hydride (HD) (v
      = 1, j = 2) collides with molecular deuterium (D2) to form HD (v = 1, j = 1),
      where v and j are the vibrational and rotational quantum numbers, respectively.
      HD (v = 1, j = 2) was prepared by Stark-induced adiabatic Raman passage, with its
      bond axis aligned preferentially parallel or perpendicular to the lab-fixed
      relative velocity. The coexpansion brought the collision temperature down to 1
      kelvin, restricting scattering to s and p partial waves. Scattering angular
      distributions showed a dramatic stereodynamic preference (~3:1) for perpendicular
      versus parallel alignment. The four-vector correlation measured between the
      initial and final velocities and the initial and final rotational angular
      momentum vectors of HD provides insight into the strong anisotropic forces
      present in the collision process.

PMID- 29051379
TI  - Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction
      and inflammation.
AB  - Intestinal colonization by bacteria of oral origin has been correlated with
      several negative health outcomes, including inflammatory bowel disease. However,
      a causal role of oral bacteria ectopically colonizing the intestine remains
      unclear. Using gnotobiotic techniques, we show that strains of Klebsiella spp.
      isolated from the salivary microbiota are strong inducers of T helper 1 (TH1)
      cells when they colonize in the gut. These Klebsiella strains are resistant to
      multiple antibiotics, tend to colonize when the intestinal microbiota is
      dysbiotic, and elicit a severe gut inflammation in the context of a genetically
      susceptible host. Our findings suggest that the oral cavity may serve as a
      reservoir for potential intestinal pathobionts that can exacerbate intestinal
      disease.

PMID- 29051380
TI  - Recent natural selection causes adaptive evolution of an avian polygenic trait.
AB  - We used extensive data from a long-term study of great tits (Parus major) in the
      United Kingdom and Netherlands to better understand how genetic signatures of
      selection translate into variation in fitness and phenotypes. We found that
      genomic regions under differential selection contained candidate genes for bill
      morphology and used genetic architecture analyses to confirm that these genes,
      especially the collagen gene COL4A5, explained variation in bill length. COL4A5
      variation was associated with reproductive success, which, combined with
      spatiotemporal patterns of bill length, suggested ongoing selection for longer
      bills in the United Kingdom. Last, bill length and COL4A5 variation were
      associated with usage of feeders, suggesting that longer bills may have evolved
      in the United Kingdom as a response to supplementary feeding.

PMID- 29051381
TI  - Learning-enhanced coupling between ripple oscillations in association cortices
      and hippocampus.
AB  - Consolidation of declarative memories requires hippocampal-neocortical
      communication. Although experimental evidence supports the role of sharp-wave
      ripples in transferring hippocampal information to the neocortex, the exact
      cortical destinations and the physiological mechanisms of such transfer are not
      known. We used a conducting polymer-based conformable microelectrode array
      (NeuroGrid) to record local field potentials and neural spiking across the dorsal
      cortical surface of the rat brain, combined with silicon probe recordings in the
      hippocampus, to identify candidate physiological patterns. Parietal, midline, and
      prefrontal, but not primary cortical areas, displayed localized ripple (100 to
      150 hertz) oscillations during sleep, concurrent with hippocampal ripples.
      Coupling between hippocampal and neocortical ripples was strengthened during
      sleep following learning. These findings suggest that ripple-ripple coupling
      supports hippocampal-association cortical transfer of memory traces.

PMID- 29051382
TI  - Destruction and reformation of an iron-sulfur cluster during catalysis by lipoyl
      synthase.
AB  - Lipoyl synthase (LipA) catalyzes the last step in the biosynthesis of the lipoyl
      cofactor, which is the attachment of two sulfhydryl groups to C6 and C8 of a
      pendant octanoyl chain. The appended sulfur atoms derive from an auxiliary [4Fe
      4S] cluster on the protein that is degraded during turnover, limiting LipA to one
      turnover in vitro. We found that the Escherichia coli iron-sulfur (Fe-S) cluster
      carrier protein NfuA efficiently reconstitutes the auxiliary cluster during LipA
      catalysis in a step that is not rate-limiting. We also found evidence for a
      second pathway for cluster regeneration involving the E. coli protein IscU. These
      results show that enzymes that degrade their Fe-S clusters as a sulfur source can
      nonetheless act catalytically. Our results also explain why patients with NFU1
      gene deletions exhibit phenotypes that are indicative of lipoyl cofactor
      deficiencies.

PMID- 29051384
TI  - Taxon-restricted genes at the origin of a novel trait allowing access to a new
      environment.
AB  - Taxon-restricted genes make up a considerable proportion of genomes, yet their
      contribution to phenotypic evolution is poorly understood. We combined gene
      expression with functional and behavioral assays to study the origin and adaptive
      value of an evolutionary innovation exclusive to the water strider genus
      Rhagovelia: the propelling fan. We discovered that two taxon-restricted genes,
      which we named geisha and mother-of-geisha, specifically control fan development.
      geisha originated through a duplication event at the base of the Rhagovelia
      lineage, and both duplicates acquired a novel expression in a specific cell
      population prefiguring fan development. These gene duplicates played a central
      role in Rhagovelia's adaptation to a new physical environment, demonstrating that
      the evolution of taxon-restricted genes can contribute directly to evolutionary
      novelties that allow access to unexploited ecological niches.

PMID- 29051383
TI  - D4 dopamine receptor high-resolution structures enable the discovery of selective
      agonists.
AB  - Dopamine receptors are implicated in the pathogenesis and treatment of nearly
      every neuropsychiatric disorder. Although thousands of drugs interact with these
      receptors, our molecular understanding of dopaminergic drug selectivity and
      design remains clouded. To illuminate dopamine receptor structure, function, and
      ligand recognition, we determined crystal structures of the D4 dopamine receptor
      in its inactive state bound to the antipsychotic drug nemonapride, with
      resolutions up to 1.95 angstroms. These structures suggest a mechanism for the
      control of constitutive signaling, and their unusually high resolution enabled a
      structure-based campaign for new agonists of the D4 dopamine receptor. The
      ability to efficiently exploit structure for specific probe discovery-rapidly
      moving from elucidating receptor structure to discovering previously
      unrecognized, selective agonists-testifies to the power of structure-based
      approaches.

PMID- 29051385
TI  - From patients to partners.

PMID- 29051386
TI  - Ets2 anchors the prometastatic function of mutant p53 in osteosarcoma.
AB  - Mutations in the tumor suppressor p53 occur in a majority of human cancers. Some
      gain-of-function (GOF) p53 mutations endow tumor cells with increased metastatic
      ability, although our understanding of the underlying mechanism remains
      incomplete. In this issue of Genes & Development, Pourebrahim and colleagues (pp.
      1847-1857) develop a new mouse model of osteosarcoma in which a GOF mutant p53
      allele is expressed specifically in osteoblasts, while the tumor microenvironment
      remains wild type for p53, allowing for the study of cell-autonomous functions.
      In this model, the role of GOF mutant p53 in promoting lung metastasis is shown
      to be critically dependent on the transcription factor Ets2 and is accompanied by
      the elevated expression of a cluster of small nucleolar RNAs (snoRNAs).

PMID- 29051387
TI  - Out of the testis: biological impacts of new genes.
AB  - The study of newly evolved genes has long fascinated biologists, but large-scale
      studies of their expression dynamics and molecular function have provided
      conflicting interpretations of their biological impact. In this issue of Genes &
      Development, Kondo and colleagues (pp. 1841-1846) use extensive transcriptomic
      resources and current CRISPR/Cas9 technology to re-examine the functional impact
      of newly evolved genes in Drosophila and find evidence of their biological impact
      on male reproduction.

PMID- 29051390
TI  - Corrigendum: The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a
      putative tumor suppressor through selective regulation of gene expression.

PMID- 29051388
TI  - A conduit to metastasis: circulating tumor cell biology.
AB  - Advances in the enrichment and analysis of rare cells from the bloodstream have
      allowed for detection and characterization of circulating tumor cells (CTCs) from
      patients with cancer. The analysis of CTCs has provided significant insight into
      the metastatic process. Studies on the biology of CTCs have begun to elucidate
      the molecular mechanisms of CTC generation, intravasation, survival, interactions
      with components of the blood, extravasation, and colonization of distant organs.
      Additionally, the study of CTCs has exposed dramatic intrapatient and
      interpatient heterogeneity and their evolution over time. In this review, we
      focus on the current knowledge of CTC biology and the potential clinical
      implications.

PMID- 29051389
TI  - New genes often acquire male-specific functions but rarely become essential in
      Drosophila.
AB  - Relatively little is known about the in vivo functions of newly emerging genes,
      especially in metazoans. Although prior RNAi studies reported prevalent lethality
      among young gene knockdowns, our phylogenomic analyses reveal that young
      Drosophila genes are frequently restricted to the nonessential male reproductive
      system. We performed large-scale CRISPR/Cas9 mutagenesis of "conserved,
      essential" and "young, RNAi-lethal" genes and broadly confirmed the lethality of
      the former but the viability of the latter. Nevertheless, certain young gene
      mutants exhibit defective spermatogenesis and/or male sterility. Moreover, we
      detected widespread signatures of positive selection on young male-biased genes.
      Thus, young genes have a preferential impact on male reproductive system
      function.

PMID- 29051391
TI  - Trace eyeblink conditioning is associated with changes in synaptophysin
      immunoreactivity in the cerebellar interpositus nucleus in guinea pigs.
AB  - Synaptic plasticity plays a role during trace eyeblink conditioning (TEBC).
      Synaptophysin (Syn) is a major integral transmembrane protein, located
      particularly in the synaptic vesicles, and is considered a molecular marker of
      synapses. In addition, Syn immunoreactivity is an important indicator of synaptic
      plasticity. In the present study, we used immunohistochemical techniques to
      assess changes in Syn expression in the cerebellar interpositus nucleus (IN) of
      guinea pigs exposed to TEBC and pseudoconditioning. Additionally, we analyzed the
      relationship between Syn immunoreactivity and the percentage of trace-conditioned
      responses. Guinea pigs underwent trace conditioning or pseudoconditioning.
      Following two, six, or ten sessions, they were perfused and the cerebellum was
      removed for Syn immunohistochemical evaluation. After sessions 6 and 10, a
      significant increase in conditioned response (CR) percentage was observed in the
      trace-conditioned group, with the CR percentage reaching the learning criteria
      following session 10. Besides, for trace-conditioned animals, the Syn expression
      in IN was found significantly up-regulated after session 10 compared with
      pseudoconditioned ones. Our data suggest that the increase in Syn expression
      links to synaptic plasticity changes in the cerebellar IN and provides a
      histological substrate in the IN relating to TEBC training. The changing trend of
      Syn immunoreactivity in the IN is associated with CR percentage.

PMID- 29051392
TI  - Recent discoveries from the cosmic microwave background: a review of recent
      progress.
AB  - Measurements of the anisotropies in the cosmic microwave background (CMB)
      radiation have provided a wealth of information about the cosmological model that
      describes the contents and evolution of the universe. These data have led to a
      standard model described by just six parameters. In this review we focus on
      discoveries made in the past decade from satellite and ground-based experiments,
      and look ahead to those anticipated in the coming decade. We provide an
      introduction to the key CMB observables including temperature and polarization
      anisotropies, and describe recent progress towards understanding the initial
      conditions of structure formation, and establishing the properties of the
      contents of the universe including neutrinos. Results are now being derived both
      from the primordial CMB signal that traces the behavior of the universe at 400
      000 years of cosmic time, as well as from the signals imprinted at later times
      due to scattering from galaxy clusters, from the motion of electrons in the
      ionized universe, and from the gravitational lensing of the CMB photons. We
      describe current experimental methods to measure the CMB, particularly focusing
      on details relevant for ground and balloon-based instruments, and give an
      overview of the broad data analysis methods required to convert measurements of
      the microwave sky into cosmological parameters.

PMID- 29051393
TI  - 4-Dimensional Tracking with Ultra-Fast Silicon Detectors.
AB  - The evolution of particle detectors has always pushed the technological limit in
      order to provide enabling technologies to researchers in all fields of science.
      One archetypal example is the evolution of silicon detectors, from a system with
      a few channels 30 years ago, to the tens of millions of independent pixels
      currently used to track charged particles in all major particle physics
      experiments. Nowadays, silicon detectors are ubiquitous not only in research
      laboratories but in almost every high tech apparatus, from portable phones to
      hospitals. In this contribution, we present a new direction in the evolution of
      silicon detectors for charge particle tracking, namely the inclusion of very
      accurate timing information. This change in the present silicon detector paradigm
      is enabled by the inclusion of controlled, low gain in the detector response,
      therefore enhancing the detector output signal enough to make timing measurement
      possible. After providing a short overview of the advantage of this new
      technology, we present the necessary conditions that need to be met for the
      sensor and for the electronics in order to achieve 4-dimensional tracking. In the
      last section we present the experimental results, demonstrating the validity of
      our research path.

PMID- 29051394
TI  - Key issues review: evolution on rugged adaptive landscapes.
AB  - Adaptive landscapes represent a mapping between genotype and fitness. Rugged
      adaptive landscapes contain two or more adaptive peaks: allele combinations with
      higher fitness than any of their neighbors in the genetic space. How do
      populations evolve on such rugged landscapes? Evolutionary biologists have
      struggled with this question since it was first introduced in the 1930s by Sewall
      Wright. Discoveries in the fields of genetics and biochemistry inspired various
      mathematical models of adaptive landscapes. The development of landscape models
      led to numerous theoretical studies analyzing evolution on rugged landscapes
      under different biological conditions. The large body of theoretical work
      suggests that adaptive landscapes are major determinants of the progress and
      outcome of evolutionary processes. Recent technological advances in molecular
      biology and microbiology allow experimenters to measure adaptive values of large
      sets of allele combinations and construct empirical adaptive landscapes for the
      first time. Such empirical landscapes have already been generated in bacteria,
      yeast, viruses, and fungi, and are contributing to new insights about evolution
      on adaptive landscapes. In this Key Issues Review we will: (i) introduce the
      concept of adaptive landscapes; (ii) review the major theoretical studies of
      evolution on rugged landscapes; (iii) review some of the recently obtained
      empirical adaptive landscapes; (iv) discuss recent mathematical and statistical
      analyses motivated by empirical adaptive landscapes, as well as provide the
      reader with instructions and source code to implement simulations of evolution on
      adaptive landscapes; and (v) discuss possible future directions for this exciting
      field.

PMID- 29051395
TI  - Role of computer tomography and endoscopic ultrasonography in assessing portal
      and superior mesenteric vessels invasion in cephalo-pancreatic adenocarcinoma.
AB  - AIM: The aim of this study is to evaluate the information given by contrast
      enhanced computer tomography (CECT) and ultrasound endoscopy (EUS) regarding
      vascular involvement of cephalo-pancreatic cancer, data compared with
      intraoperative findings. MATERIAL AND METHODS: We choose to analyze the most
      often interested vessels by tumor development, such as superior mesenteric artery
      (SMA), superior mesenteric vein (SMV) and portal vein (PV). The patients included
      in the study (n=425) had a cephalo-pancreatic tumor diagnosed in our Institute
      and a positive histology for pancreatic adenocarcinoma. The exclusion criteria
      were: tumors in sites other than the head of the pancreas (including metastases);
      tumor involvement of common hepatic artery, celiac trunk, inferior cava vein or
      aorta; CECT or EUS diagnosis performed in another center; and a delay of more
      than 35 days between the diagnostic imaging and surgery. RESULTS: In diagnosing
      SMA invasion CECT had an accuracy of 84,92% and EUS had an accuracy of 87,39%. In
      diagnosing PV and SMV involvement, CECT had an accuracy of 84,83% and EUS had an
      accuracy of 92,17%. The accuracy of the two combined examinations in diagnosing
      vascular invasion was 93%. CONCLUSONS: Both types of examination have showed good
      accuracies in diagnosing vascular invasion separately. A combination of the two
      may be used when the CECT result is uncertain as it provides a higher chance of a
      correct diagnosis. KEY WORDS: Pancreatic cancer, Resectability criteria, Vascular
      invasion.

PMID- 29051396
TI  - Facial transplantation. An update of results and perspectives from tissue
      engineering.
AB  - BACKGROUND/AIM: Facial transplantation is a revolutionary procedure developed
      recently, which is indicated if autologous transfers fail to restore human
      appearance. More than 30 patients have undergone facial transplantation in
      different centers worldwide. Here, we provide an update on its main anatomical,
      surgical, immunological, ethical, and follow- up aspects. We also provide
      innovative perspectives of regenerative medicine and tissue engineering that
      could hold promise for this emerging surgical field. METHODS: Through careful
      review of the anatomical, surgical, and tissue-engineering literature, we
      documented the main aspects of this innovative surgical procedure and its
      potential improvements in regenerative plastic surgery. RESULTS: Compatibility
      for the major blood groups (ABO) and human leukocyte antigen system between donor
      and recipient is critical to transplantation success. Major complications are
      tissue rejection and side effects of immunosuppression. The functional outcomes
      of facial transplantation are encouraging, with slow recovery of motor and
      sensory functions. Psychological impact on the family of the donor and recipient
      is essential for the success of facial transplantation. CONCLUSIONS: Uncertainty
      of long-term outcomes, immunosuppression-related concerns and ethical debates
      limit worldwide application of facial allotransplantation. However, in selected
      patients it is a unique reconstruction method with promising outcomes. Recent
      developments in regenerative medicine open a new frontier for application of
      patient-tailored, biocompatible and engineered reproductions of the various
      anatomical components of the face, and their application to transplant
      technology. Further research in transplant immunology, survival and conservation
      of grafts, and regenerative treatments of lesioned and/or transplanted tissues
      hold the key to advances in this emerging surgical option. KEY WORDS: Facial
      transplantation, Plastic surgery, Reconstructive surgery, , Regenerative
      medicine, Tssue engineering.

PMID- 29051397
TI  - In situ preservation of the partathyroid glands in total thyroidectomy: a
      propensity score matched analysis.
AB  - AIM: Severe hypocalcemia due to parathyroid gland damage may be a serious
      complication after thyroidectomy. In order to save parathyroid integrity we
      developed a no-touch parathyroid (NTP) thyroidectomy technique. METHODS: We
      performed a total extracapsular thyroidectomy with NTP technique in consecutive
      50 cases of benign goiter between July 2014 and June 2015. Parathyroid glands
      were firstly indentified, then they were separated from the thyroid avoiding
      manipulation or trauma and preserving their vascularization. Traditional scissors
      were preferentially used for dissection around the glands. Patients operated with
      NTP technique were matched by a propensity score to a control group. RESULTS: NTP
      was feasible in all foreseen patients except one. Propensity score selected a
      group of 23 patients/group for matching. No mortality has been observed in either
      group. Operative time were comparable between groups. Blood loss were
      significantly less abundant in the NTP group. No laryngeal permanent paralysis
      was experienced. Hospital stay was shorter yet not significantly in NTP group.
      Neither hypocalcemic crisis nor permanent hypoparathyroidism were described in
      either group. Serum calcium levels (NTP Vs control) were significantly higher in
      NTP group at day 1 (p=0.03) and day 2 (p=0.002), respectively. Similarly, intact
      parathormone dosages were significantly higher at day 1 (p=0.004) and day 7
      (p=0.001), respectively. CONCLUSIONS: We conclude that NTP thyroidectomy is a
      feasible in the majority of the patientsand, allows a significant reduction of
      blood loss without prolonging the operative time. After the procedureboth values
      of calcemia and intact parathormonewere stable and no hypocalcemic crisis was
      experienced. KEY WORDS: Parathyroid, Hypoparathyroidism, Hypocalcemia, Total
      thyroidectomy.

PMID- 29051398
TI  - Relationship between postoperative complications and survival after gastrectomy
      for cancer.
AB  - BACKGROUND: Surgical resection remains the main curative treatment for gastric
      cancer but is still affected by high postoperative morbidity and mortality rates,
      especially in Western countries. MATERIALS AND METHODS: We've analyzed patients
      treated for gastric cancer at our Operative Unit of ent, extent of
      lymphadenectomy and survival. General Surgery and Organ Transplantation of the
      University Hospital of Parma from January 2006 till December 2010, relating the
      occurrence of eventual complications to sex, age at diagnosis, definitive
      histological examination, type and duration of surgical treatment. RESULTS: The
      surgically treated cases were 152 (30.4 gastrectomies per year on average). 62
      patients developed at least one adverse event during the postoperative period,
      reaching 108 total events. Among these, 71 were minor complications (grade I-II
      in Clavien-Dindo's classification), while 26 were major ones (grade III).
      Postoperative mortality affected 8 patients (5.3%). Data analysis did not stress
      any statistically significant correlation between the valued variables and the
      global incidence of complications. For severe ones, some risk factors emerged
      such as the type of gastrectomy, the execution of a multi-visceral resection and
      the operative time. Five-year overall survival has been 36.7%, lower in patients
      with severe complications (29%) when compared to patients without severe
      complications (38%). Radicality of operation, the lymph node involvement and the
      occurrence of severe complication emerged as significant prognostic factors for
      five-year overall survival. CONCLUSIONS: Surgery is still the mainstay of
      treatment for gastric cancer and the only one able to grant a curative therapy.
      When performed in high-volume centres, with more than 20 gastrectomies per year,
      it represents a safe treatment, affected by low mortality. Attention must be paid
      to careful preoperative selection, to treatment of pre-existent comorbidities, to
      plan a therapeutical strategy to minimize surgical stress, to postoperative
      monitoring and to managing complications', as they're able to impact not only low
      term outcomes but also overall and disease-free survival. The poor prognosis for
      these patients is mainly related to advanced stage at presentation, thus
      confirming the need to increase early diagnosis in order to detect in larger
      percentages the tumor in its early stage. KEY WORDS: Complications, Gastrectomy,
      Gastric Cancer, Survival.

PMID- 29051399
TI  - The impact of gallbladder retrieval from an epigastric vs. umbilical port on
      trocar-site complications A prospective randomized study.
AB  - AIM: Port-site infection and hernias are among the most of the complications
      following laparoscopic cholecystectomy (LC). Although surgical technique of LC is
      described to obtain critical view of safety, there is still no consensus on ideal
      portsite for gallbladder retrieval. In this comparative study, we aimed to
      investigate the effects of gallbladder retrieval site on postoperative port site
      complications following LC. MATERIAL AND METHODS: In this prospective randomized
      study, 120 patients underwent LC for symptomatic gallbladder disease. Standard 4
      port LC was routinely performed. Patients were divided into two groups
      consecutively. The gallbladder was removed through the umbilical port-site in
      Group A (n=60) and the epigastric port-site in Group B (n=60). Postoperative port
      site complications were recorded. Visual analogue scale (VAS) for pain was also
      applied to the patients on the postoperative day 1, 10 and 30. RESULTS:
      Demographic features were similar in both groups. Postoperative pain in terms of
      VAS score was significantly lower for Group B on the postoperative day 1 and 30
      (p=0.019, and p=0.001 respectively). The need for enlargement and time of GB
      retrieval was similar between groups. There is no statistical difference in terms
      of port-site infection or hernia between groups. CONCLUSIONS: The findings of
      this study provide epigastric port retrieval in terms of plausible reasons
      including significantly lower postoperative pain scores in both short- and long
      term and quite lower trocar site-related complications. Key words: Gallbladder
      disease, Laparoscopic cholecystectomy, Port-site complications.

PMID- 29051400
TI  - How to eliminate bilateral cleft lip stigmata 30 year experience.
AB  - PURPOSE: To report a surgical algorithm for the treatment of bilateral cleft lip
      stigmata. METHODS: The investigators designs a retrospective study composed of
      patients with bilateral cleft lip stigmata. The surgical approach is on the basis
      of the severity of the deformity and of course the age of the patient. It
      consists in Simple scar revision with orbicularis muscle synthesis; Two dermal
      flaps tunneled in the central vermilion; Abbe flap. The investigators analyzes
      early and late complications, and performs the evaluation of the cosmetic
      appearance by a parent or patient himself/herself, a surgeon and a blinded third
      party observer. RESULTS: The sample was composed of 351 patients. At short-term
      follow-up, viability of the flaps, function and morphology are good. At long-term
      follow-up, we observed significant improvement of the characteristics and profile
      of the patient's face and a normal function of the lips. We recorded a good
      scarring and a high satisfaction rate by evaluation of patients/ surgeon/ blinded
      third party observer. CONCLUSION: The results of this study suggest that a
      surgical algorithm on the basis of the severity of the deformity and of course
      the age of the patient can represent an option of choice for most patients with
      bilateral cleft lip stigmata. KEY WORDS: Abbe flap, Bilateral cleft lip stigmata,
      Cleft lip, Dermal flaps, Orbicularis muscles.

PMID- 29051401
TI  - Symptomatic pile tailored procedure. A new perspective for hemorrhoidal disease
      treatment.
AB  - AIM: Aim of the present paper was to evaluate the role of tailored different
      single pile treatment in the clinical outcome of hemorrhoids. MATERIAL OF STUDY:
      The surgical strategy considered to treat only pathological piles with different
      procedure according to each pathological Goligher's degree, presence of fibrous,
      inelastic redundant internal pile(F) and presence of external pathological pile
      (external pile congestion or subversion of dental line (E) and skin tag not
      tolerated from the patient (S)). We treated with Hemorrhoidopexy second and third
      degree pile without F or ES; with Hemorrhoidopexy and excision of external
      component every second and third degree pile with E or S and with complete semi
      closed pile excision all third degree with F and IV degree piles. The number of
      post operative days of self administered analgesics was the primary end point and
      short/long term post operative complications, hospital stay, re-admission and
      recurrence were secondary end points. RESULTS: 157 patients were treated. No
      differences were noted in term of time of discharge between hemorrhoidopexy and
      complete or external excision. The painkiller assumption increases with the
      number of treated pile (r= 0.227, p=0.006). We observed 10.2% early complications
      (48h) all secondary to urinary retention and 7% late complications (2-15days)
      within only one reoperation for bleeding. After mean follow up of 16 months no
      patients required further treatments for hemorrhoids. DISCUSSIONS: A tailored
      approach showed to be effective in terms of short and long term complications and
      moreover to relapse. CONCLUSIONS: Single pile tailored treatment showed good
      results. KEY WORDS: Excision, Hemorrhoids, Hemorrhoidectomy, Hemorrhoidopexy,
      Pain, Tailored.

PMID- 29051402
TI  - T-tube biliary drainage during reconstruction after pancreaticoduodenectomy. A
      single-center experience.
AB  - AIM: The purpose of this study is to communicate our experience about the results
      and effectiveness in the use of the Ttube biliary drainage during
      pancreaticoduodenectomy. MATERIAL OF STUDY: In accordance whit Whipple we perform
      the gastric antrum resection during pancreaticoduodenectomy. We have treated 42
      patients with pancreaticoduodenectomy, 25 males and 17 females with a mean age of
      62 years (range: 53-79 years), and in each of them we have placed a biliary T
      tube. RESULTS: Pancreatic fistula was the most common complication and occurred
      in 10 patients (23.81%), all of these were low-flow fistula (<200 ml) and
      required only medical treatment. DISCUSSION: Resection of the pancreas is
      considered a major operative procedure. Pancreatic fistula is the most common
      complication after pancreaticoduodenectomy, and it was also the most frequent
      complication observed by us. In pancreaticoduodenectomy T-tube allows lesser
      risks of complications due to pancreatic fistula and it makes its faster healing.
      In all cases the treatment was not invasive. CONCLUSIONS: T-tube biliary drainage
      can make a positive contribution concerning all the complications that can occur
      after pancreaticoduodenectomy, especially against the pancreatic fistula. KEY
      WORDS: Pancreaticoduodenectomy, Pancreatic fistula, Pancreas head cancer,
      Pancreatic Tumors, T-tube drainage.

PMID- 29051403
TI  - Axillary treatment of patients with breast cancer and micrometastatic disease in
      the sentinel lymph node Our experience.
AB  - AIM: Since the introduction of the sentinel lymph node biopsy (SLNB) in patients
      with breast cancer, micrometastases are detected frequently in the sln. PATIENTS
      AND METHODS: Between July 2005 and June 2016, 1244 patients were submitted to
      surgery for breast cancer. 431 patients cT1-2 N0 underwent to sentinel lymph node
      (SLN) and micrometastases were found in 68 of 431 screen-detected patients.
      Nearly all patients with both micro and macrometastases had axillary lymph node
      dissection (ALND). RESULTS: The SLN was negative in 69% of patients (296 of 431),
      121 patients (28%) instead turned positive for lymph node metastases and in 14
      patients (3%) were identified isolated tumor cells (ITC). SLN micrometastases
      were detected in 15,7% of patients (68 of 431). All patients with micrometastases
      underwent a completion ALND. In 85% of cases, therefore, the sentinel node with
      micrometastases was the only site of nodal disease. Neither loco-regional
      recurrences or distant metastases occurred in any of the Patients with sln
      micrometastases. DISCUSSION: There is considerable interest in foregoing axillary
      dissection (AD) when the sentinel node (SN) is positive in early breast cancer,
      particularly when axillary involvement is minimal (micrometastases or isolated
      tumor cells). Several trials are addressing the problem. In breast cancer
      patients survival is not affected by the presence of micrometastatic lymph node
      involvement. CONCLUSION: In our experience we always underwent to ALND all
      patients with micrometastases. In the light of the results we observed our
      attitude no longer provides for the axillary lymphadenectomy. KEY WORDS: Axillary
      dissection ,Breast cancer, Sentinel Lymph Node Biopsy.

PMID- 29051404
TI  - Complications after parotid gland surgery Our experience.
AB  - AIM: Complications after parotid surgery include deficit of the facial nerve,
      wound complications, as sialocele and salivary fistula, and Frey syndrome; the
      goal of this study was to evaluate the relationship between the type of parotid
      surgery performed and the incidence of each of these complications. MATERIAL OF
      STUDY: A total of 184 patients were evaluated and 158 were included in the study.
      Four different kinds of intervention were made: extracapsular dissection, partial
      superficial parotidectomy; superficial parotidectomy and total parotidectomy. The
      incidence of each complication was studied and correlated to the type of surgery
      performed. Statistical analysis was done using the chi-square test of
      independence. RESULTS: From all cases examined, 86 patients developed facial
      nerve complications with 59 minor asymmetry, 19 partial weakness and 8 complete
      weakness. Forty patients had wound complications, 28 sialocele and 12 salivary
      fistula. Sixteen patients developed Frey syndrome. DISCUSSION: Facial nerve
      complications and Frey syndrome were significantly related to superficial or
      total parotidectomy, differently extracapsular dissection and partial superficial
      parotidectomy had more cases of wound complications. CONCLUSION: The kind of
      complications that occur after parotid surgery depends on surgery performed. Chi
      square test has a statistically significant result and confirms this kind of
      relationship (P <.0001). KEY WORDS: Facial nerve, Parotid glands, Parotidectomy.

PMID- 29051405
TI  - Suggestions for a standard clinical practice curriculum and learning objectives
      for physical therapy education in Korea.

PMID- 29051406
TI  - Does the acceptance of hybrid learning affect learning approaches in France?
AB  - PURPOSE: Acceptance of a learning technology affects students' intention to use
      that technology, but the influence of the acceptance of a learning technology on
      learning approaches has not been investigated in the literature. A deep learning
      approach is important in the field of health, where links must be created between
      skills, knowledge, and habits. Our hypothesis was that acceptance of a hybrid
      learning model would affect students' way of learning. METHODS: We analysed these
      concepts, and their correlations, in the context of a flipped classroom method
      using a local learning management system. In a sample of all students within a
      single year of study in the midwifery program (n= 38), we used 3 validated scales
      to evaluate these concepts (the Study Process Questionnaire, My Intellectual Work
      Tools, and the Hybrid E-Learning Acceptance Model: Learner Perceptions). RESULTS:
      Our sample had a positive acceptance of the learning model, but a neutral
      intention to use it. Students reported that they were distractible during
      distance learning. They presented a better mean score for the deep approach than
      for the superficial approach (P< 0.001), which is consistent with their declared
      learning strategies (personal reorganization of information; search and use of
      examples). There was no correlation between poor acceptance of the learning model
      and inadequate learning approaches. The strategy of using deep learning
      techniques was moderately correlated with acceptance of the learning model (rs=
      0.42, P= 0.03). CONCLUSION: Learning approaches were not affected by acceptance
      of a hybrid learning model, due to the flexibility of the tool. However, we
      identified problems in the students' time utilization, which explains their
      neutral intention to use the system.

PMID- 29051407
TI  - Farmers' Exposure to Pesticides: Toxicity Types and Ways of Prevention.
AB  - Synthetic pesticides are extensively used in agriculture to control harmful pests
      and prevent crop yield losses or product damage. Because of high biological
      activity and, in certain cases, long persistence in the environment, pesticides
      may cause undesirable effects to human health and to the environment. Farmers are
      routinely exposed to high levels of pesticides, usually much greater than those
      of consumers. Farmers' exposure mainly occurs during the preparation and
      application of the pesticide spray solutions and during the cleaning-up of
      spraying equipment. Farmers who mix, load, and spray pesticides can be exposed to
      these chemicals due to spills and splashes, direct spray contact as a result of
      faulty or missing protective equipment, or even drift. However, farmers can be
      also exposed to pesticides even when performing activities not directly related
      to pesticide use. Farmers who perform manual labor in areas treated with
      pesticides can face major exposure from direct spray, drift from neighboring
      fields, or by contact with pesticide residues on the crop or soil. This kind of
      exposure is often underestimated. The dermal and inhalation routes of entry are
      typically the most common routes of farmers' exposure to pesticides. Dermal
      exposure during usual pesticide handling takes place in body areas that remain
      uncovered by protective clothing, such as the face and the hands. Farmers'
      exposure to pesticides can be reduced through less use of pesticides and through
      the correct use of the appropriate type of personal protective equipment in all
      stages of pesticide handling.

PMID- 29051409
TI  - Metal and Microelement Biomarkers of Neurodegeneration in Early Life Permethrin
      Treated Rats.
AB  - Hair is a non-invasive biological material useful in the biomonitoring of trace
      elements because it is a vehicle for substance excretion from the body, and it
      permits evaluating long-term metal exposure. Here, hair from an animal model of
      neurodegeneration, induced by early life permethrin treatment from the sixth to
      21th day of life, has been analyzed with the aim to assess if metal and
      microelement content could be used as biomarkers. A hair trace element assay was
      performed by the ICP-MS technique in six- and 12-month-old rats. A significant
      increase of As, Mg, S and Zn was measured in the permethrin-treated group at 12
      months compared to six months, while Si and Cu/Zn were decreased. K, Cu/Zn and S
      were increased in the treated group compared to age-matched controls at six and
      12 months, respectively. Cr significantly decreased in the treated group at 12
      months. PCA analysis showed both a best difference between treated and age
      matched control groups at six months. The present findings support the evidence
      that the Cu/Zn ratio and K, measured at six months, are the best biomarkers for
      neurodegeneration. This study supports the use of hair analysis to identify
      biomarkers of neurodegeneration induced by early life permethrin pesticide
      exposure.

PMID- 29051410
TI  - Contributing Factors for Acute Illness/Injury from Childhood Pesticide Exposure
      in North Carolina, USA, 2007-2013.
AB  - Between 2007 and 2013, there were 685 events with evidence of a relationship
      between pesticide exposure and acute illness/injury among persons less than 18
      years old in North Carolina (United States). Median age of children affected was
      4.3 years (range: 0.2-17.9). Distribution by gender was similar across all age
      groups. One fatality and four high severity events were observed. The greatest
      proportion (42%) of events had ocular exposures, followed by dermal (25%) and
      inhalation (18%) exposures. When more than one route of exposure occurred, dermal
      and ocular routes were the most common (46%). Almost all events took place
      indoors and 32 events involved contact with pets. Insecticides (53%) and insect
      repellants (31%) were the most frequent agents contributing to these events.
      Manual application of pesticides contributed to the greatest number of events
      (25%), while application through a pressurized can and use of a trigger pump were
      involved in 21% and 15% of events, respectively. Additional contributors were due
      to inappropriate storage of pesticides and improper use of the pesticide. These
      contributing factors can be removed or minimized if pesticides are stored outside
      the residence or out of the reach of children and pets, and adequate ventilation
      is ensured whenever pesticides are applied.

PMID- 29051411
TI  - Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS): A New Tool for the
      Analysis of Toxicological Effects on Single Cell Level.
AB  - Single cell imaging mass spectrometry opens up a complete new perspective for
      strategies in toxicological risk assessment and drug discovery. In particular,
      time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial
      and depth resolution is becoming part of the imaging mass spectrometry toolbox
      used for single cell analysis. Recent instrumentation advancements in combination
      with newly developed cluster ion guns allow 3-dimensional reconstruction of
      single cells together with a spatially resolved compound location and
      quantification on nanoscale depth level. The exact location and quantification of
      a single compound or even of a set of compounds is no longer restricted to the
      two dimensional space within single cells, but is available for voxels, a cube
      sized 3-dimensional space, rather than pixels. The information gathered from one
      voxel is further analysed using multivariate statistical methodology like maximum
      autocorrelation factors to co-locate the compounds of interest within
      intracellular organelles like nucleus, mitochondria or golgi apparatus.
      Furthermore, the cell membrane may be resolved, including adhering compounds and
      potential changes of the lipid patterns. The generated information can be used
      further for a first evaluation of intracellular target specifity of new drug
      candidates or for the toxicological risk assessment of environmental chemicals
      and their intracellular metabolites. Additionally, single cell lipidomics and
      metabolomics enable for the first time an in-depth understanding of the
      activation or inhibition of cellular biosynthesis and signalling pathways.

PMID- 29051412
TI  - Transcriptional Suppression of Renal Antioxidant Enzyme Systems in Guinea Pigs
      Exposed to Polymerized Cell-Free Hemoglobin.
AB  - Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma
      volume-expanding therapeutics though their potential to promote oxidative tissue
      injury has raised safety concerns. Using a guinea pig exchange transfusion model,
      we examined the effects of polymerized bovine hemoglobin (HbG) on the
      transcriptional regulation, activity, and expression of the renal antioxidant
      enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms
      1-3, GPx1, GPx3, GPx4, and CAT. This transcriptional suppression correlated with
      decreased enzymatic activities for SOD, CAT, and GPx. Immunostaining revealed
      decreased protein expression of SOD1, CAT, and GPx1 primarily in renal cortical
      tubules. DNA methylation analyses identified CpG hypermethylation in the gene
      promoters for SOD1-3, GPx1, GPx3, and GPx4, suggesting an epigenetic-based
      mechanism underlying the observed gene repression. HbG also induced oxidative
      stress as evidenced by increased renal lipid peroxidation end-products and 4-HNE
      immunostaining, which could be the result of the depleted antioxidant defenses
      and/or serve as a trigger for increased DNA methylation. Together, these findings
      provide evidence that the renal exposure to HbG suppresses the function of major
      antioxidant defense systems which may have relevant implications for
      understanding the safety of hemoglobin-based products.

PMID- 29051413
TI  - Current Status of Air Toxics Management and Its Strategies for Controlling
      Emissions in Taiwan.
AB  - Since the 1970s, hazardous air pollutants (HAPs), so-called air toxics, have been
      of great concern because they can cause serious human health effects and have
      adverse effects on the environment. More noticeably, some of them are known to be
      human carcinogens. The objective of this paper is to investigate the regulatory
      systems and human health effects of air toxics which have been designated by the
      Taiwan government under the Air Pollution Control Act. These toxic air pollutants
      include acutely toxic gas (i.e., ammonia, chlorine, fluorides, hydrochloric acid,
      hydrogen cyanide, hydrogen sulfide, nitric acid, phosphoric acid and sulfuric
      acid), gas containing heavy metals, and carcinogenic chemicals (including
      formaldehyde, vinyl chloride, asbestos and matter containing asbestos, dioxins
      and furans, volatile organic compounds, polycyclic aromatic hydrocarbons, and
      polychlorinated biphenyls). In line with international concern about the
      carcinogenic risk and environmental persistence of polychlorinated dibenzo-p
      dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) and heavy metals in
      recent years, the current status in monitoring and reducing the emissions of
      PCDDs/PCDFs from stationary sources was analyzed as a case study in the present
      study. Furthermore, the control strategies for reducing emissions of air toxics
      from stationary sources in Taiwan were also addressed.

PMID- 29051414
TI  - Assessing Potential Vulnerability and Response of Fish to Simulated Avian
      Predation after Exposure to Psychotropic Pharmaceuticals.
AB  - Psychotropic pharmaceuticals present in the environment may impact organisms both
      directly and via interaction strengths with other organisms, including predators;
      therefore, this study examined the potential effects of pharmaceuticals on
      behavioral responses of fish to avian predators. Wild-caught juvenile perch
      (Perca fluviatilis) were assayed using a striking bird model after a seven-day
      exposure to psychotropic pharmaceuticals (the antidepressants fluoxetine or
      sertraline, or the beta-blocker propranolol) under the hypotheses that exposure
      would increase vulnerability to avian predation via increasing the probability of
      predator encounter as well as degrading evasive behaviors upon encounter. None of
      the substances significantly affected swimming activity of the fish, nor did they
      increase vulnerability by affecting encounter probability or evasive endpoints
      compared to control treatments. Counter to our expectations, fish exposed to 100
      MUg/L fluoxetine (but no other concentrations or pharmaceuticals) were less
      likely to enter the open area of the arena, i.e., less likely to engage in risky
      behavior that could lead to predator encounters. Additionally, all fish exposed
      to environmentally relevant, low concentrations of sertraline (0.12 MUg/L) and
      propranolol (0.1 MUg/L) sought refuge after the simulated attack. Our unexpected
      results warrant further research as they have interesting implications on how
      these psychotropic pharmaceuticals may affect predator-prey interactions spanning
      the terrestrial-aquatic interface.

PMID- 29051415
TI  - Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a
      Survey of UK Residents' Exposure.
AB  - Penconazole is a widely used fungicide in the UK; however, to date, there have
      been no peer-reviewed publications reporting human metabolism, excretion or
      biological monitoring data. The objectives of this study were to i) develop a
      robust analytical method, ii) determine biomarker levels in volunteers exposed to
      penconazole, and, finally, to iii) measure the metabolites in samples collected
      as part of a large investigation of rural residents' exposure. An LC-MS/MS method
      was developed for penconazole and two oxidative metabolites. Three volunteers
      received a single oral dose of 0.03 mg/kg body weight and timed urine samples
      were collected and analysed. The volunteer study demonstrated that both
      penconazole-OH and penconazole-COOH are excreted in humans following an oral dose
      and are viable biomarkers. Excretion is rapid with a half-life of less than four
      hours. Mean recovery of the administered dose was 47% (range 33%-54%) in urine
      treated with glucuronidase to hydrolyse any conjugates. The results from the
      residents' study showed that levels of penconazole-COOH in this population were
      low with >80% below the limit of detection. Future sampling strategies that
      include both end of exposure and next day urine samples, as well as contextual
      data about the route and time of exposure, are recommended.

PMID- 29051416
TI  - UNMIX Methods Applied to Characterize Sources of Volatile Organic Compounds in
      Toronto, Ontario.
AB  - UNMIX, a sensor modeling routine from the U.S. Environmental Protection Agency
      (EPA), was used to model volatile organic compound (VOC) receptors in four urban
      sites in Toronto, Ontario. VOC ambient concentration data acquired in 2000-2009
      for 175 VOC species in four air quality monitoring stations were analyzed. UNMIX,
      by performing multiple modeling attempts upon varying VOC menus-while rejecting
      the results that were not reliable-allowed for discriminating sources by their
      most consistent chemical characteristics. The method assessed occurrences of VOCs
      in sources typical of the urban environment (traffic, evaporative emissions of
      fuels, banks of fugitive inert gases), industrial point sources (plastic-,
      polymer-, and metalworking manufactures), and in secondary sources (releases from
      water, sediments, and contaminated urban soil). The remote sensing and robust
      modeling used here produces chemical profiles of putative VOC sources that, if
      combined with known environmental fates of VOCs, can be used to assign physical
      sources' shares of VOCs emissions into the atmosphere. This in turn provides a
      means of assessing the impact of environmental policies on one hand, and
      industrial activities on the other hand, on VOC air pollution.

PMID- 29051417
TI  - Household Air Pollution: Sources and Exposure Levels to Fine Particulate Matter
      in Nairobi Slums.
AB  - With 2.8 billion biomass users globally, household air pollution remains a public
      health threat in many low- and middle-income countries. However, little evidence
      on pollution levels and health effects exists in low-income settings, especially
      slums. This study assesses the levels and sources of household air pollution in
      the urban slums of Nairobi. This cross-sectional study was embedded in a
      prospective cohort of pregnant women living in two slum areas-Korogocho and
      Viwandani-in Nairobi. Data on fuel and stove types and ventilation use come from
      1058 households, while air quality data based on the particulate matters (PM2.5)
      level were collected in a sub-sample of 72 households using the DustTrakTM II
      Model 8532 monitor. We measured PM2.5 levels mainly during daytime and using
      sources of indoor air pollutions. The majority of the households used kerosene
      (69.7%) as a cooking fuel. In households where air quality was monitored, the
      mean PM2.5 levels were high and varied widely, especially during the evenings
      (124.6 ug/m3 SD: 372.7 in Korogocho and 82.2 ug/m3 SD: 249.9 in Viwandani), and
      in households using charcoal (126.5 ug/m3 SD: 434.7 in Korogocho and 75.7 ug/m3
      SD: 323.0 in Viwandani). Overall, the mean PM2.5 levels measured within homes at
      both sites (Korogocho = 108.9 ug/m3 SD: 371.2; Viwandani = 59.3 ug/m3 SD: 234.1)
      were high. Residents of the two slums are exposed to high levels of PM2.5 in
      their homes. We recommend interventions, especially those focusing on clean
      cookstoves and lighting fuels to mitigate indoor levels of fine particles.

PMID- 29051418
TI  - Toxicities of Therapeutic Agents Used in Medicine.
AB  - This Special Issue on "Toxicities of Therapeutic Agents Used in Medicine" reports
      on some peculiar cases of toxicities related to widely and commonly employed
      drugs.[...].

PMID- 29051419
TI  - Toxicovigilance Systems and Practices in Africa.
AB  - African consumers and citizens are growingly aware of the wide range of toxic
      poisoning scenarios from different products and hazards. Recurrent episodes on
      poisoning that have been reported in Africa include toxic hazards in consumers'
      products ranging from food to herbal medicine, drugs, and cosmetics. Chemical
      poisoning remains an issue that is overlooked by public health stakeholders in
      Africa. Available information on toxicovigilance systems and practices in African
      countries is reviewed in terms of increasing development, organization and
      articulation levels. Less than nine out of 54 African countries have a legally
      recognized toxicovigilance system. Of these, the majority have created
      toxicovigilance systems recently, and are facing many challenges in developing
      them, at regional and country levels. Basic structures for a good toxicovigilance
      system include a phone line service (available 24/7), and hospital facilities.
      Pesticides emerge as the hazard recognized by all of the toxicovigilance systems,
      and may represent a prototypic toxicant towards a toxicovigilance system that is
      inclusive of a wider spectrum of toxicological hazards for the protection of
      community health. Toxicovigilance today is more reactive than preventive in
      Africa, but some milestones are present that constitute some promising seminal
      efforts.

PMID- 29051420
TI  - Air Quality and Hospital Outcomes in Emergency Medical Admissions with
      Respiratory Disease.
AB  - BACKGROUND: The impact of very low levels of air pollutants, particulate matter
      (PM10) and sulfur dioxide (SO2) concentrations, on human health is not well
      characterized. We examined the outcomes (30-day in-hospital mortality) of
      emergency hospitalizations of respiratory patients and the level of local
      pollutants on the day of admission. METHODS: All emergency admissions (82,421
      episodes in 44,660 patients) were recorded over 13 years (2002-2014) and
      mortality assessed. The median interquartile ranges (IQR) age was 64.5 (43.9,
      78.5) years with the proportion of males at 48.5%. Univariate and multivariate
      logistic regression was used to examine relationships between pollutant
      concentration (PM10 and SO2) and odds ratio (OR) for 30-day in hospital death,
      after adjustment for acuity. RESULTS: Mortality related to each pollutant
      variable assessed (as quintiles of increasing atmospheric concentration). For
      PM10 mortality, the highest two quintiles concentrations were significantly
      increased (p < 0.001) with univariate ORs of 1.30. For SO2, the ORs were 1.32,
      1.39, and 1.46, for the top three quintiles. There was also a strong relationship
      between the underlying respiratory function; with forced expiratory volume (FEV1)
      in 1 second (FEV1) >= 2.0L at the lowest PM10 quintile, mortality was 6.5% (95%
      CI: 6.1, 6.9) increasing to 9.5% (95% CI: 9.0, 10.0) at the highest PM10
      quintile. For patients with FEV1 < 2.0L, the mortality at the lowest PM10
      quintile was 9.9% (95% CI: 8.8, 10.9) increasing to 14.2% (95% CI: 12.8, 15.6) at
      the highest quintile. CONCLUSION: Despite air quality improvement, there was a
      clear relationship between pollutant concentration and outcomes for respiratory
      emergency admissions; additionally, the underlying level of pulmonary function
      was predictive of in-hospital mortality.

PMID- 29051421
TI  - Groundwater Contamination by Uranium and Mercury at the Ridaura Aquifer (Girona,
      NE Spain).
AB  - Elevated concentrations of uranium and mercury have been detected in drinking
      water from public supply and agricultural wells in alluvial and granitic aquifers
      of the Ridaura basin located at Catalan Coastal Ranges (CCR). The samples showed
      high concentrations of U above the U.S. standards and the World Health
      Organization regulations which set a maximum value of 30 ug/L. Further, high
      mercury concentrations above the European Drinking Water Standards (1 MUg/L) were
      found. Spatial distribution of U in groundwater and geochemical evolution of
      groundwater suggest that U levels appear to be highest in granitic areas where
      groundwater has long residence times and a significant salinity. The presence of
      high U concentrations in alluvial groundwater samples could be associated with
      hydraulic connection through fractures between the alluvial system and deep
      granite system. According to this model, oxidizing groundwater moving through
      fractures in the leucocratic/biotitic granite containing anomalous U contents are
      the most likely to acquire high levels of U. The distribution of Hg showed
      concentrations above 1 MUg/L in 10 alluvial samples, mainly located near the
      limit of alluvial aquifer with igneous rocks, which suggests a possible migration
      of Hg from granitic materials. Also, some samples showed Hg concentrations
      comprised between 0.9 and 1.5 MUg/L, from wells located in agricultural areas.

PMID- 29051422
TI  - Impact of Spent Mushroom Substrates on the Fate of Pesticides in Soil, and Their
      Use for Preventing and/or Controlling Soil and Water Contamination: A Review.
AB  - Intensive crop production involves a high consumption of pesticides. This is a
      cause of major environmental concern because the presence of pesticides in water
      is becoming increasingly common. Physicochemical methods based on soil
      modification with organic residues have been developed to enhance the
      immobilization and/or degradation of pesticides in agricultural soils, which may
      control both the diffuse and the point pollution of soils and waters. This review
      summarizes the influence of spent mushroom substrate (SMS) on the environmental
      fate of pesticides when both are simultaneously applied in agriculture. The
      processes of adsorption, leaching and dissipation of these compounds in SMS
      amended soils were evaluated at laboratory and field scale. Relationships were
      established between the experimental parameters obtained and the properties of
      the soils, the SMS, and the pesticides in order to determine the effect that the
      application of SMS in agricultural soils has on the environmental impact of
      pesticides. Accordingly, this review highlights the use of SMS as a strategy for
      the prevention and/or control of soil and water contamination by pesticides to
      strike a balance between agricultural development and the use of these compounds.

PMID- 29051424
TI  - Evaluation of Common Use Brominated Flame Retardant (BFR) Toxicity Using a
      Zebrafish Embryo Model.
AB  - Brominated flame retardants (BFRs) are used to reduce the flammability of
      plastics, textiles, and electronics. BFRs vary in their chemical properties and
      structures, and it is expected that these differences alter their biological
      interactions and toxicity. Zebrafish were used as the model organism for
      assessing the toxicity of nine structurally-diverse BFRs. In addition to
      monitoring for overt toxicity, the rate of spontaneous movement, and
      acetylcholinesterase and glutathione-S-transferase (GST) activities were assessed
      following exposure. The toxicities of BFRs tested can be ranked by LC50 as
      tetrabromobisphenol A (TBBPA) < 4,4'-isopropylidenebis[2-(2,6
      dibromophenoxyl)ethanol] (TBBPA-OHEE) < Pentabromochlorocyclohexane (PBCH) < 2
      ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) < hexabromocyclododecane (HBCD) <
      hexabromobenzene (HBB) < Tetrabromophthalic anhydride (PHT4). No adverse effect
      was observed in di(2-ethylhexyl) tetrabromophthalate (TBPH) or dibromoneopentyl
      glycol (DBNPG)-treated embryos. The rate of spontaneous movement was decreased in
      a concentration-dependent manner following exposure to four of the nine
      compounds. GST activity was elevated following treatment with PBCH, TBBPA, HBCD,
      and HBB. The results indicate that exposure to several BFRs may activate an
      antioxidant response and alter behavior during early development. Some of the
      BFRs, such as TBBPA and TBBPA-OHEE, induced adverse effects at concentrations
      lower than chemicals that are currently banned. These results suggest that
      zebrafish are sensitive to exposure to BFRs and can be used as a comparative
      screening model, as well as to determine alterations in behavior following
      exposure and probe mechanisms of action.

PMID- 29051425
TI  - Differences in Reproductive Behavior between Spawning and Non-Spawning Zebrafish
      Pairs and the Effects of 17alpha-Ethinylestradiol (EE2).
AB  - Reproductive success manifested by spawning and fertilization, in most fish,
      depends partly on an appropriate courtship behavior by both sexes. The zebrafish
      reproductive behavior can be resolved in some of its constituent elements by a
      computerized vision system and described in unbiased quantitative terms. Pairs of
      adult male and female zebrafish were monitored with automatic video tracking at
      16 Hz for 45 min in a tank with a spawning area in one corner. Subsequently,
      spawning, if any, was registered and the swimming behavior and mutual
      interactions of the two fish were quantified. Further, temporal and frequency
      distributions of average velocity and turning rate were produced. It is
      demonstrated that the courtship behavior in spawning pairs differs markedly from
      non-spawning pairs with differences in both male and female behavior. EE2
      (17alpha-ethinylestradiol), a contraceptive hormone found in aquatic
      environments, has only a slight effect on these behavior differences between
      spawning and non-spawning pairs.

PMID- 29051423
TI  - The Synapse as a Central Target for Neurodevelopmental Susceptibility to
      Pesticides.
AB  - The developmental period of the nervous system is carefully orchestrated and
      highly vulnerable to alterations. One crucial factor of a properly-functioning
      nervous system is the synapse, as synaptic signaling is critical for the
      formation and maturation of neural circuits. Studies show that genetic and
      environmental impacts can affect diverse components of synaptic function.
      Importantly, synaptic dysfunction is known to be associated with neurologic and
      psychiatric disorders, as well as more subtle cognitive, psychomotor, and sensory
      defects. Given the importance of the synapse in numerous domains, we wanted to
      delineate the effects of pesticide exposure on synaptic function. In this review,
      we summarize current epidemiologic and molecular studies that demonstrate
      organochlorine, organophosphate, and pyrethroid pesticide exposures target the
      developing synapse. We postulate that the synapse plays a central role in
      synaptic vulnerability to pesticide exposure during neurodevelopment, and the
      synapse is a worthy candidate for investigating more subtle effects of chronic
      pesticide exposure in future studies.

PMID- 29051426
TI  - Effects of Estrogen, Nitric Oxide, and Dopamine on Behavioral Locomotor
      Activities in the Embryonic Zebrafish: A Pharmacological Study.
AB  - Nitric oxide (NO) has been shown to affect motor function. Specifically, NO has
      been shown to act through regulation of dopamine (DA) release, transporter
      function, and the elicitation of neuroprotection/neurodegeneration of neurons.
      Recently, zebrafish have been proposed to be a new model for the study of various
      types of motor dysfunctions, since neurotoxin damage to their nigrostriatal-like
      neurons exhibit motor anomalies similar to those of mammalian models and human
      patients. Results from this study demonstrate that when NO synthesis is inhibited
      in zebrafish, using a neuronal NO synthase inhibitor (nNOSI), a condition called
      'listless' occurs, where the fish lack swimming abilities, are rigid, and have
      difficulty maintaining balance. Additionally, co-treatment with either NO or
      estrogen (E2), an upstream regulator of NO synthase, can rescue fish from the
      'listless' phenotype caused by exposure to the neurotoxin 6-hydroxydopamine (6
      OHDA). In turn, NO deprived zebrafish were rescued from the 'listless' phenotype
      when co-treated with L-DOPA, a precursor to DA. Interestingly, the longer fish
      are exposed to a 6 OHDA + nNOSI co-treatment, the slower the recovery after
      washout, compared to a single treatment of each. Most significantly, NO
      involvement in the motor homeostasis of the embryonic zebrafish was shown to be
      expressed through the NO-cGMP-dependent pathway, and response to nNOSI treatments
      is developmentally regulated. In conclusion, these results indicate that there is
      a link between E2, NO, and DA systems that regulate motor functions in the
      embryonic zebrafish.

PMID- 29051427
TI  - Developmental Bisphenol A Exposure Modulates Immune-Related Diseases.
AB  - Bisphenol A (BPA), used in polycarbonate plastics and epoxy resins, has a
      widespread exposure to humans. BPA is of concern for developmental exposure
      resulting in immunomodulation and disease development due to its ability to cross
      the placental barrier and presence in breast milk. BPA can use various mechanisms
      to modulate the immune system and affect diseases, including agonistic and
      antagonistic effects on many receptors (e.g., estrogen receptors), epigenetic
      modifications, acting on cell signaling pathways and, likely, the gut microbiome.
      Immune cell populations and function from the innate and adaptive immune system
      are altered by developmental BPA exposure, including decreased T regulatory
      (Treg) cells and upregulated pro- and anti-inflammatory cytokines and chemokines.
      Developmental BPA exposure can also contribute to the development of type 2
      diabetes mellitus, allergy, asthma and mammary cancer disease by altering immune
      function. Multiple sclerosis and type 1 diabetes mellitus may also be exacerbated
      by BPA, although more research is needed. Additionally, BPA analogs, such as
      bisphenol S (BPS), have been increasing in use, and currently, little is known
      about their immune effects. Therefore, more studies should be conducted to
      determine if developmental exposure BPA and its analogs modulate immune responses
      and lead to immune-related diseases.

PMID- 29051428
TI  - Association of Long-Term Pesticide Exposure and Biologic Parameters in Female
      Farm Workers in Tanzania: A Cross Sectional Study.
AB  - The study aimed to assess the association of long-term pesticide exposure (>=5
      years) with hematological, serum biochemical parameters and acetylcholinesterase
      activity in farm workers. These pesticides included organophosphorus pesticides,
      carbamates, pyrethroids, dithiocarbamates, and other pesticides such as
      endosulfan. Applying a cross-sectional study design, 69 females from a pesticide
      exposed farm population and 30 females from a district not using pesticides
      (reference group) were studied. The mean red cell corpuscular volume and
      hematocrit values were significantly lower (74.7 +/- 9.1 fl; 95% CI 72.5-76.9 and
      32.0% +/- 4.6%; 95% CI 30.9-33.1, respectively) in the exposed compared to the
      reference group, whereas mean corpuscular hemoglobin concentration and platelets
      were significantly higher (37.4 +/- 3.8 g/dL; 95% CI 36.5-38.3 and 374.1 +/-
      95.3/L; 95% CI 351.2-396.9, respectively) in the exposed compared to the
      reference group. Mean serum glutamic oxaloacetate transaminase (20.7 +/- 8.9 U/L;
      95% CI 18.5-22.9) and creatinine (83.9 +/- 6.6 MUmol/L; 95% CI 82.3-85.5) were
      significantly higher in the exposed compared to the reference group. A higher
      mean esterase activity (AChE 0.6 +/- 0.2 mM/min/mg protein; 95% CI 0.56-0.7; BChE
      0.9 +/- 0.4 mM/min/mg protein; 95% CI 0.9-1.1) was noted in the exposed group.
      Regression models suggest that occupational exposure (p < 0.001) could be a
      predictor of esterase (AChE and BChE) activity and biochemical changes (beta =
      0.4, 95% CI: 0.3-0.5; beta = 0.7, 95% CI: 0.6-0.9, respectively). Long-term
      pesticide exposure affects the hemato-biochemical and esterase responses,
      establishing the need for further studies.

PMID- 29051429
TI  - Fish Reproduction Is Disrupted upon Lifelong Exposure to Environmental PAHs
      Fractions Revealing Different Modes of Action.
AB  - Polycyclic aromatic hydrocarbons (PAHs) constitute a large family of organic
      pollutants emitted in the environment as complex mixtures, the compositions of
      which depend on origin. Among a wide range of physiological defects, PAHs are
      suspected to be involved in disruption of reproduction. In an aquatic
      environment, the trophic route is an important source of chronic exposure to
      PAHs. Here, we performed trophic exposure of zebrafish to three fractions of
      different origin, one pyrolytic and two petrogenic. Produced diets contained PAHs
      at environmental concentrations. Reproductive traits were analyzed at individual,
      tissue and molecular levels. Reproductive success and cumulative eggs number were
      disrupted after exposure to all three fractions, albeit to various extents
      depending on the fraction and concentrations. Histological analyses revealed
      ovary maturation defects after exposure to all three fractions as well as
      degeneration after exposure to a pyrolytic fraction. In testis, hypoplasia was
      observed after exposure to petrogenic fractions. Genes expression analysis in
      gonads has allowed us to establish common pathways such as endocrine disruption
      or differentiation/maturation defects. Taken altogether, these results indicate
      that PAHs can indeed disrupt fish reproduction and that different fractions
      trigger different pathways resulting in different effects.

PMID- 29051430
TI  - Hair Microelement Profile as a Prognostic Tool in Parkinson's Disease.
AB  - Changes in the homeostasis of metals and microelements have been demonstrated in
      Parkinson's disease, whose etiology includes both a genetic and environmental
      basis. We studied the difference of microelements in the hair of Parkinson's
      disease subjects (n = 46) compared with healthy controls (n = 24). Hair was
      chosen as a representative matrix to measure microelements, since it is a vehicle
      of substance excretion from the human body and it allows for long-term evaluation
      of metal exposure. An inductively coupled plasma mass spectrometry (ICP-MS)
      analysis of hair collected from 24 Parkinson's patients compared with their
      healthy relatives used as controls shows a significant decrease in Ca (U = 166, p
      = 0.012),), Mg (U = 187, p = 0.037), and Sr (U = 183, p = 0.030). Cd and Ca/Mg
      were decreased, and Cu was increased, in patients with respect to their healthy
      related controls at the limit of significance (p = 0.0501). Principal Component
      Analysis (PCA) of these microelements in hair shows a clustering into two groups
      according to gender, disease severity according to the Hoehn-Yahr scale, and
      pharmacological therapy. This pilot study represents a starting point for future
      investigations where a larger group of subjects will be involved to define other
      microelements useful when screening for early biomarkers of Parkinson's disease.

PMID- 29051431
TI  - Haematological, Biochemical and Antioxidant Changes in Wistar Rats Exposed to
      Dichlorvos Based Insecticide Formulation Used in Southeast Nigeria.
AB  - The indiscriminate use of pesticide is a treat to non-target organisms. This
      study evaluates the haematological and biochemical changes induced by inhalation
      of local Nigerian dichlorvos insecticide on rats. The rats were randomly assigned
      to a control group which received only food and water and a test group which, in
      addition to food and water, was exposed to the pesticide for a period of 4 h
      daily for 28 days, after which exposure was discontinued for seven days. Five
      animals were sacrificed from each group on days 1, 7, 14, 21, 28 and 35, and
      blood was collected by cardiac puncture for haematological, biochemical and
      antioxidant analysis. Results obtained showed lowered values of red blood cell
      count (RBC), packed cell volume (PCV), haemoglobin, mean cell haemoglobin (MCH)
      and mean cell haemoglobin concentration (MCHC) (p < 0.05) with increased white
      blood cell count (WBC) and platelet counts after day 14 when compared to the
      control group. Liver enzymes aspartate amino transaminase (AST) and alanine amino
      transaminase (ALT) were higher in the exposed rats compared to the control group
      (p < 0.05). Urea and creatinine concentrations increased significantly after day
      1 and at day 28, while superoxide dismutase (SOD), gluthathione (GSH) and
      catalase (CAT) activity increased significantly compared to the control after day
      1, day 14 and day 21, respectively. The RBC, PCV and haemoglobin values of all
      exposed rats were restored to normal following withdrawal of the pesticide,
      though AST, ALT, urea, creatinine and, glutathione values remained significantly
      high compared to the control. Inhalation of the local insecticide is toxic to the
      blood, liver and kidney of laboratory rats and may be deleterious to human health
      following long-term exposure.

PMID- 29051433
TI  - A Review of Heavy Metal Concentration and Potential Health Implications of
      Beverages Consumed in Nigeria.
AB  - Beverages are consumed in Nigeria irrespective of age, sex, and socioeconomic
      status. Beverages may be alcoholic (wine, spirits, and beers) or non-alcoholic
      (soft drink, energy drinks, candies, chocolates, milks). Notwithstanding, most
      beverages are packed in cans, bottles, and plastics. This paper reviews the
      concentration of heavy metals from some commercially-packaged beverages consumed
      in Nigeria. The study found that heavy metal concentrations, including iron,
      mercury, tin, antimony, cadmium, zinc, copper, chromium, lead, and manganese,
      seldom exceed the maximum contaminant level recommended by the Standard
      Organization of Nigeria (SON) and the World Health Organization (WHO) as
      applicable to drinking water resources. The occurrence of heavy metals in the
      beverages could have resulted from the feedstocks and water used in their
      production. Consumption of beverages high in heavy metal could be toxic and cause
      adverse effect to human health, depending on the rate of exposure and
      accumulation dosage. This study concludes by suggesting that heavy metal
      concentration in the feedstocks and water should be monitored by producers, and
      its concentration in beverages should also be monitored by appropriate regulatory
      agencies.

PMID- 29051432
TI  - Drug Vaping: From the Dangers of Misuse to New Therapeutic Devices.
AB  - Users of e-cigarettes are unwitting volunteers participating in a worldwide
      epidemiological study. Because of the obvious benefits of e-cigarettes compared
      with traditional cigarette smoking, these electronic devices have been introduced
      all around the world to support tobacco smoking cessation. Same potential harm
      reduction could be considered by cannabis vaping for marijuana smokers. However,
      the toxicities of liquids and aerosols remain under investigation because
      although the use of e-cigarettes is likely to be less harmful than traditional
      cigarette smoking, trace levels of contaminants have been identified.
      Simultaneously, other electronic devices, such as e-vaporisers, e-hookahs or e
      pipes, have been developed and commercialised. Consequently, misuse of electronic
      devices has increased, and experimentation has been documented on Internet web
      fora. Although legal and illegal drugs are currently consumed with these e
      devices, no scientific papers are available to support the observations reported
      by numerous media and web fora. Moreover, building on illegal drug vaping and
      vaporisation with e-devices (vaping misuse), legal drug vaping (an alternative
      use of vaping) could present therapeutic benefits, as occurs with medical
      cannabis vaporisation with table vaporisers. This review seeks to synthesise the
      problems of e-cigarette and liquid refill toxicity in order to introduce the
      dangers of illegal and legal drugs consumed using vaping and vaporisation for
      recreational purposes, and finally, to present the potential therapeutic benefits
      of vaping as a new administration route for legal drugs.

PMID- 29051434
TI  - Comparative Analysis between Ecotoxicity of Nitrogen-, Phosphorus-, and Potassium
      Based Fertilizers and Their Active Ingredients.
AB  - This study aimed to analyze the ecotoxicity of nitrogen-, phosphorus-, and
      potassium-based compounds to organisms of two different trophic levels in order
      to compare the toxic effect between high-purity substances and these substances
      as components of fertilizers. Dilutions were made with the fertilizers' potassium
      chloride, potassium nitrate, superphosphate, urea, and their equivalent reagents,
      to conduct assays to establish the acute lethal concentration for half of the
      population (LC50). Ten individuals of the benthic snail Biomphalaria glabrata and
      the fish Danio rerio were exposed to each concentration of tested compounds. As a
      result, the toxicity levels of potassium chloride, potassium nitrate, and urea
      were obtained for B. glabrata and D. rerio, with the fish being more susceptible
      to potassium chloride in the fertilizer and the snail to potassium nitrate and
      urea, in both commercial and reagent forms. Regarding superphosphate, no
      significant toxicity was found. This study concluded that among the tested
      substances, KNO3 and KCl were the most toxic substances and urea the least toxic.
      It was not possible to establish the most sensitive species since, for KCl, the
      fish were more susceptible to the fertilizer and the snail to the reagent, while
      for KNO3 the opposite was observed.

PMID- 29051435
TI  - Urinary Naphthol as a Biomarker of Exposure: Results from an Oral Exposure to
      Carbaryl and Workers Occupationally Exposed to Naphthalene.
AB  - Urinary naphthol is an established human biomarker used for assessing both
      occupational and environmental exposure. However, 1-naphthol is a metabolite of
      the insecticide carbaryl while both the 1- and 2-isomers are metabolites of
      naphthalene. Thus, urinary 1-naphthol levels will reflect combined exposure to
      both substances, particularly at environmental levels. The interpretation of
      biomarkers is aided by knowledge of levels following well-characterised exposure
      scenarios. This study reports urinary 1-naphthol levels in five volunteers
      administered an oral dose of carbaryl at the acceptable daily intake (ADI, 0.008
      mg/kg). The elimination half-life was 3.6 h and the mean 1-naphthol level in 24 h
      total urine collections, normalised for a 70 kg individual, was 37.4 umol/mol
      creatinine (range 21.3-84.3). Peak levels in spot-urine samples were around 200
      umol/mol creatinine. For comparison, 327 post-shift urine samples obtained from
      90 individual workers exposed occupationally to naphthalene had 1-naphthol levels
      from below the limit of detection (<LoD) to 1027 umol/mol creatinine (median =
      4.2, mean = 27.2). The 2-naphthol levels ranged from <LoD to 153 umol/mol
      creatinine (median = 4.0, mean = 8.1). Background ranges have been reported for
      urine naphthols in several populations, with upper limits between 10 and 20
      umol/mol creatinine. The data reported here suggest that environmental exposure
      to carbaryl and naphthalene in these populations is well controlled.

PMID- 29051437
TI  - Tannery Effluent Treatment by Yeast Species Isolates from Watermelon.
AB  - The quest for an effective alternative means for effluent treatment is a major
      concern of the modern-day scientist. Fungi have been attracting a growing
      interest for the biological treatment of industrial wastewater. In this study,
      Saccharomycescerevisiae and Torulasporadelbrueckii were isolated from spoiled
      watermelon and inoculated into different concentrations of effluent. The
      inoculants were incubated for 21-days to monitor the performance of the isolates
      by measurement of biochemical oxygen demand (BOD), chemical oxygen demand (COD),
      nitrates, conductivity, phosphates, sulphates and turbidity. The results showed
      that Saccharomycescerevisiae had the highest percentage decrease of 98.1%, 83.0%,
      60.7%, 60.5%, and 54.2% for turbidity, sulphates, BOD, phosphates and COD,
      respectively, of the tannery effluent. Torulasporadelbrueckii showed the highest
      percentage decrease of 92.9%, 90.6%, and 61.9% for sulphates, COD, and
      phosphates, respectively, while the syndicate showed the highest percentage
      reduction of 87.4% and 70.2% for nitrate and total dissolve solid (TDS),
      respectively. The least percentage decrease was displayed by syndicate organisms
      at 51.2%, 48.1% and 40.3% for BOD, COD and conductivity, respectively. The study
      revealed that Saccharomycescerevisiae and Torulasporadelbrueckii could be used in
      the biological treatment of tannery-effluent. Hence, it was concluded that the
      use of these organisms could contribute to minimizing the adverse environmental
      risks and health-hazards associated with the disposal of untreated tannery
      effluents.

PMID- 29051438
TI  - EDCs Mixtures: A Stealthy Hazard for Human Health?
AB  - Endocrine disrupting chemicals (EDCs) are exogenous chemicals that may occur
      naturally (e.g., phytoestrogens), while others are industrial substances and
      plasticizers commonly utilized worldwide to which human exposure, particularly at
      low-doses, is omnipresent, persistent and occurs in complex mixtures. EDCs can
      interfere with/or mimic estrogenic hormones and, consequently, can simultaneously
      trigger diverse signaling pathways which result in diverse and divergent
      biological responses. Additionally, EDCs can also bioaccumulate in lipid
      compartments of the organism forming a mixed "body burden" of contaminants.
      Although the independent action of chemicals has been considered the main
      principle in EDCs mixture toxicity, recent studies have demonstrated that
      numerous effects cannot be predicted when analyzing single compounds
      independently. Co-exposure to these agents, particularly in critical windows of
      exposure, may induce hazardous health effects potentially associated with a
      complex "body burden" of different origins. Here, we performed an exhaustive
      review of the available literature regarding EDCs mixtures exposure, toxicity
      mechanisms and effects, particularly at the most vulnerable human life stages.
      Although the assessment of potential risks to human health due to exposure to
      EDCs mixtures is a major topic for consumer safety, information regarding
      effective mixtures effects is still scarce.

PMID- 29051439
TI  - Current Mercury Exposure from Artisanal and Small-Scale Gold Mining in Bombana,
      Southeast Sulawesi, Indonesia-Future Significant Health Risks.
AB  - The rapid expansion of the artisanal and small-scale gold mining (ASGM) industry
      in developing countries has marginalized the local communities in poverty, and
      resulted in occupational exposure to mercury via the gold extraction process. We
      investigated the mercury exposure of the mining workers lived inside and outside
      the mining area. Based on the occupations of the contributors, the hair samples
      were divided into three subgroups: directly exposed, indirectly exposed, and a
      control. A total of 81 hair samples were analyzed by particle-induced X-ray
      emission spectrometry. The median mercury concentration was highest in the hair
      from the directly exposed group (12.82 MUg/g hair) (control group median: 4.8
      MUg/g hair, p < 0.05), and the concentrations in hair from 45 respondents
      exceeded the Human Biomonitoring I (HBM I) threshold limit. Mercury
      concentrations were also elevated in the hair from the indirectly exposed group
      (median 7.64 MUg/g hair, p < 0.05), and concentrations in hair from 24
      respondents exceeded the HBM I threshold limits. Exposure to mercury during ASGM
      presents health risks and is harmful for the miners; mercury is also at hazardous
      levels for people who live in the mining area but who are not engaged in mercury
      based gold extraction.

PMID- 29051441
TI  - The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene-Two Emerging
      Potential Human Carcinogens?
AB  - For decades, compounds present in foods and beverages have been implicated in the
      etiology of human cancers. The World Health Organization (WHO) International
      Agency for Research on Cancer (IARC) continues to classify such agents regarding
      their potential carcinogenicity in humans based on new evidence from animal and
      human studies. Furfuryl alcohol and beta-myrcene are potential human carcinogens
      due to be evaluated. The major source of furfuryl alcohol in foods is thermal
      processing and ageing of alcoholic beverages, while beta-myrcene occurs naturally
      as a constituent of the essential oils of plants such as hops, lemongrass, and
      derived products. This study aimed to summarize the occurrence of furfuryl
      alcohol and beta-myrcene in foods and beverages using literature review data.
      Additionally, results of furfuryl alcohol occurrence from our own nuclear
      magnetic resonance (NMR) analysis are included. The highest content of furfuryl
      alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about
      10 mg/kg), while among beverages, wines contained between 1 and 10 mg/L, with 8
      mg/L in pineapple juice. The content of beta-myrcene was highest in hops. In
      conclusion, the data about the occurrence of the two agents is currently judged
      as insufficient for exposure and risk assessment. The results of this study point
      out the food and beverage groups that may be considered for future monitoring of
      furfuryl alcohol and beta-myrcene.

PMID- 29051440
TI  - Cytotoxic and Inflammatory Potential of Air Samples from Occupational Settings
      with Exposure to Organic Dust.
AB  - Organic dust and related microbial exposures are the main inducers of several
      respiratory symptoms. Occupational exposure to organic dust is very common and
      has been reported in diverse settings. In vitro tests using relevant cell
      cultures can be very useful for characterizing the toxicity of complex mixtures
      present in the air of occupational environments such as organic dust. In this
      study, the cell viability and the inflammatory response, as measured by the
      production of pro-inflammatory cytokines tumor necrosis factor-alpha (TNFalpha)
      and interleukin-1 beta (IL-1beta), were determined in human macrophages derived
      from THP-1 monocytic cells. These cells were exposed to air samples from five
      occupational settings known to possess high levels of contamination of organic
      dust: poultry and swine feed industries, waste sorting, poultry production and
      slaughterhouses. Additionally, fungi and particle contamination of those settings
      was studied to better characterize the organic dust composition. All air samples
      collected from the assessed workplaces caused both cytotoxic and pro-inflammatory
      effects. The highest responses were observed in the feed industry, particularly
      in swine feed production. This study emphasizes the importance of measuring the
      organic dust/mixture effects in occupational settings and suggests that
      differences in the organic dust content may result in differences in health
      effects for exposed workers.

PMID- 29051442
TI  - Pharmaceutical Wastewater Effluent-Source of Contaminants of Emerging Concern:
      Phytotoxicity of Metronidazole to Soybean (Glycine max).
AB  - Industrial discharge of active pharmaceutical ingredients (APIs) into the
      environment in some middle- and low-income countries is not sufficiently
      regulated. The phytotoxicity of metronidazole (FLAGYL)-one of the most commonly
      used over the counter (OTC) antibiotics, to soybean (Glycine max) is
      investigated. Relative growth rate (RGR) expressed in gram per gram per day (gg
      1d-1) was applied to plants destructively harvested at maturity (42 d), to
      determine the toxicological impact. Differences between mean RGR of the three
      groups were performed at 0.05 significance level. Multiple comparisons suggest
      that there was a statistical significant difference among mean RGR for all
      treatment groups. Metronidazole is toxic to soybean plants (Glycine max) based on
      dose-response criterion. There is a need to enforce treatment of pharmaceutical
      wastewater effluent by Pharmaceutical Manufacturing Companies (PMCs) before
      discharge into the environment.

PMID- 29051443
TI  - Vitis vinifera Extract Ameliorate Hepatic and Renal Dysfunction Induced by
      Dexamethasone in Albino Rats.
AB  - This study was conducted to evaluate the biochemical effects of grape seed
      extract against dexamethasone-induced hepatic and renal dysfunction in a female
      albino rat. Twenty-eight adult female rats were divided randomly into four equal
      groups: Group 1: animals were injected subcutaneously with saline and consider as
      normal control one. Group 2: animals were injected subcutaneously with
      dexamethasone in a dose of 0.1 mg/kg body weight. Group 3: animals were injected
      subcutaneously with 0.1 mg/kg body weight of dexamethasone, and then treated with
      a grape seed extract in a dose of 200 mg/kg body weight by oral gavage. Group 4:
      animals were injected subcutaneously with 0.1 mg/kg body weight of dexamethasone,
      and then treated with a grape seed extract in a dose of 400 mg/kg body weight by
      oral gavage. After 4 weeks, serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) activities, albumin, uric acid, creatinine, and glucose
      levels were assayed. Hepatic reduced glutathione (GSH), total protein content,
      and catalase and glucose-6-phosphate dehydrogenase activities were also assayed.
      Dexamethasone administration caused elevation of serum levels of glucose, uric
      acid, creatinine, ALT, AST activities, and a decrease in other parameters such as
      hepatic glutathione, total protein levels, and catalase enzyme activity.
      Treatment with Vitis vinifera L. seed extract showed a significant increase in
      the body weight of rats in the group treated with Vitis vinifera L. seed extract
      orally compared with the dexamethasone control group. An increase in GSH and
      catalase activity in response to oral treatment with Vitis vinifera L. seed
      extract was observed after treatment. Grape seed extract positively affects
      glucocorticoid-induced hepatic and renal alteration in albino rats.

PMID- 29051445
TI  - Concentrations of Polybrominated Diphenyl Ethers (PBDEs) in Water from Asunle
      Stream, Ile-Ife, Nigeria.
AB  - This study assessed the concentrations of polybrominated diphenylethers (PBDEs)
      in stream water obtained from Asunle stream, an adjoining stream of the Obafemi
      Awolowo University dumpsite. Water samples were collected for a period of eight
      months from six different locations comprising of a spot upstream in an uphill
      area relative to the refuse dumpsite and five others downstream along the stream
      course. The sampled waters were extracted with dicholoromethane using liquid
      liquid extraction method and cleanup was carried out with silica gel. The final
      extracts after concentration were analyzed using GC-MS/MS. The recovery
      experiments were adequate (105%-110%). The mean levels of ?6PBDEs compounds
      analyzed ranged from 0.03 to 0.45 ng/mL. Seasonal variability of PBDEs indicated
      that higher levels were found during the wet season. The levels of PBDEs recorded
      in this work were relatively lower compared to the values reported in the
      literature from other developed nations.

PMID- 29051444
TI  - The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological
      Monitoring Urinary Speciation Analysis.
AB  - This study investigates the identity of two unexpected arsenic species found
      separately in a number of urine samples sent to the Health and Safety Executive's
      Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite,
      As3+; arsenate, As5+; monomethylarsonic acid, MMA5+; and dimethylarsinic acid,
      DMA5+). Micro liquid chromatography coupled to inductively coupled plasma mass
      spectrometry (uLC-ICP-MS) and electrospray time of flight tandem mass
      spectrometry (ESI-QqTOF-MS/MS) were used to identify the two arsenic peaks by
      comparison to several characterized arsenicals: arsenocholine, AC; trimethyl
      arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE;
      thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio
      dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF
      MS/MS investigations indicate that the unexpected arsenic species termed peak 1
      was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be
      identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio
      DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected
      arsenic species in both routine and non-routine urine samples from both workers
      and hospital patients.

PMID- 29051446
TI  - Characterization of Aerosols of Titanium Dioxide Nanoparticles Following Three
      Generation Methods Using an Optimized Aerosolization System Designed for
      Experimental Inhalation Studies.
AB  - Nanoparticles (NPs) can be released in the air in work settings, but various
      factors influence the exposure of workers. Controlled inhalation experiments can
      thus be conducted in an attempt to reproduce real-life exposure conditions and
      assess inhalation toxicology. Methods exist to generate aerosols, but it remains
      difficult to obtain nano-sized and stable aerosols suitable for inhalation
      experiments. The goal of this work was to characterize aerosols of titanium
      dioxide (TiO2) NPs, generated using a novel inhalation system equipped with three
      types of generators-a wet collision jet nebulizer, a dry dust jet and an
      electrospray aerosolizer-with the aim of producing stable aerosols with a nano
      diameter average (<100 nm) and monodispersed distribution for future rodent
      exposures and toxicological studies. Results showed the ability of the three
      generation systems to provide good and stable dispersions of NPs, applicable for
      acute (continuous up to 8 h) and repeated (21-day) exposures. In all cases, the
      generated aerosols were composed mainly of small aggregates/agglomerates (average
      diameter <100 nm) with the electrospray producing the finest (average diameter of
      70-75 mm) and least concentrated aerosols (between 0.150 and 2.5 mg/m3). The dust
      jet was able to produce concentrations varying from 1.5 to 150 mg/m3, and hence,
      the most highly concentrated aerosols. The nebulizer collision jet aerosolizer
      was the most versatile generator, producing both low (0.5 mg/m3) and relatively
      high concentrations (30 mg/m3). The three optimized generators appeared suited
      for possible toxicological studies of inhaled NPs.

PMID- 29051447
TI  - Revelation of Different Nanoparticle-Uptake Behavior in Two Standard Cell Lines
      NIH/3T3 and A549 by Flow Cytometry and Time-Lapse Imaging.
AB  - The uptake of nanomaterials into different cell types is a central
      pharmacological issue for the determination of nanotoxicity as well as for the
      development of drug delivery strategies. Most responses of the cells depend on
      their intracellular interactions with nanoparticles (NPs). Uptake behavior can be
      precisely investigated in vitro, with sensitive high throughput methods such as
      flow cytometry. In this study, we investigated two different standard cell lines,
      human lung carcinoma (A549) and mouse fibroblast (NIH/3T3) cells, regarding their
      uptake behavior of titanium dioxide NPs. Cells were incubated with different
      concentrations of TiO2 NPs and samples were taken at certain time points to
      compare the uptake kinetics of both cell lines. Samples were analyzed with the
      help of flow cytometry by studying changes in the side and forward scattering
      signal. To additionally enable a detection via fluorescence, NPs were labeled
      with the fluorescent dye fluorescein isothiocyanate (FITC) and propidium iodide
      (PI). We found that NIH/3T3 cells take up the studied NPs more efficiently than
      A549 cells. These findings were supported by time-lapse microscopic imaging of
      the cells incubated with TiO2 NPs. Our results confirm that the uptake behavior
      of individual cell types has to be considered before interpreting any results of
      nanomaterial studies.

PMID- 29051448
TI  - North Carolina Toxic Substance Incidents Program 2010-2015: Identifying Areas for
      Injury Prevention Efforts.
AB  - The National Toxic Substance Incidents Program (NTSIP) is a surveillance system
      designed to capture acute toxic substance releases, factors contributing to the
      release, and any associated injuries. North Carolina has participated since 2010,
      when NTSIP was established. This article will present a descriptive statistical
      summary from 2010 to 2015 focused on releases that resulted in injuries in order
      to identify areas for public health prevention efforts. Of the 1690 toxic
      releases in North Carolina, 155 incidents resulted in injuries and 500 people
      were injured. Carbon monoxide injured the greatest number of people. Of the
      incidents that resulted in injuries, 68 occurred at private vehicles or
      residences (44%), injuring 124 people (25%). Over half of events where at least
      one responder was injured occurred at private vehicles or residences. Events
      occurring at private residences did not have a significant relationship between
      evacuations and injuries, while for industry-related events, the odds of an
      evacuation being ordered were 8.18 times greater (OR = 8.18, 95% CI = 5.19,
      12.89) when there were injuries associated with an event. Intervention efforts
      should focus on preventing responder injuries while responding to private
      residence releases and educating the general public on how to prevent injuries by
      self-evacuating areas where hazardous chemicals have been released.

PMID- 29051449
TI  - Do 16 Polycyclic Aromatic Hydrocarbons Represent PAH Air Toxicity?
AB  - Estimation of carcinogenic potency based on analysis of 16 polycyclic aromatic
      hydrocarbons (PAHs) ranked by U.S. Environmental Protection Agency (EPA) is the
      most popular approach within scientific and environmental air quality management
      communities. The majority of PAH monitoring projects have been focused on
      particle-bound PAHs, ignoring the contribution of gas-phase PAHs to the toxicity
      of PAH mixtures in air samples. In this study, we analyzed the results of 13
      projects in which 88 PAHs in both gas and particle phases were collected from
      different sources (biomass burning, mining operation, and vehicle emissions), as
      well as in urban air. The aim was to investigate whether 16 particle-bound U.S.
      EPA priority PAHs adequately represented health risks of inhalation exposure to
      atmospheric PAH mixtures. PAH concentrations were converted to benzo(a)pyrene
      equivalent (BaPeq) toxicity using the toxic equivalency factor (TEF) approach.
      TEFs of PAH compounds for which such data is not available were estimated using
      TEFs of close isomers. Total BaPeq toxicities (?88BaPeq) of gas- and particle
      phase PAHs were compared with BaPeq toxicities calculated for the 16 particle
      phase EPA PAH (?16EPABaPeq). The results showed that 16 EPA particle-bound PAHs
      underrepresented the carcinogenic potency on average by 85.6% relative to the
      total (gas and particle) BaPeq toxicity of 88 PAHs. Gas-phase PAHs, like
      methylnaphthalenes, may contribute up to 30% of ?88BaPeq. Accounting for other
      individual non-EPA PAHs (i.e., benzo(e)pyrene) and gas-phase PAHs (i.e.,
      naphthalene, 1- and 2-methylnaphthalene) will make the risk assessment of PAH
      containing air samples significantly more accurate.

PMID- 29051450
TI  - Differential Effects of Low-Molecular-Weight Organic Acids on the Mobilization of
      Soil-Borne Arsenic and Trace Metals.
AB  - A batch experiment was conducted to examine the effects of six low-molecular
      weight organic acids on the mobilization of arsenic and trace metals from a range
      of contaminated soils. The results showed that the organic acids behaved
      differently when reacting with soil-borne As and trace metals. Oxalic acid and
      acetic acid had the strongest and weakest capacity to mobilize the investigated
      elements, respectively. The solubilisation of iron oxides by the organic acids
      appears to play a critical role in mobilizing other trace metals and As. Apart
      from acidification and complexation, reductive dissolution played a dominant role
      in the dissolution of iron oxides in the presence of oxalic acid, while
      acidification tended to be more important for dissolving iron oxides in the
      presence of other organic acids. The unique capacity of oxalic acid to solubilize
      iron oxides tended to affect the mobilization of other elements in different
      ways. For Cu, Mn, and Zn, acidification-driven mobilization was likely to be
      dominant while complexation might play a major role in Pb mobilization. The
      formation of soluble Fe and Pb oxalate complexes could effectively prevent
      arsenate or arsenite from combining with these metals to form solid phases of Fe
      or Pb arsenate or arsenite.

PMID- 29051451
TI  - Farmers' Training on Pesticide Use Is Associated with Elevated Safety Behavior.
AB  - Occupational exposure to pesticides in agricultural applications may cause acute
      and long-term health effects to farmers, and thus research on factors that reduce
      exposure is useful. However, studies on the relevance and effectiveness of
      training are limited. The association of previous training in the form of
      intensive seminars relating to pesticide use (e.g., use of spraying equipment,
      application parameters, use of personal protective equipment, risks to human
      health and the environment) with farmers' knowledge and behavior in pesticide use
      was studied via the self-reporting method in a purposive sample of 82 trained and
      non-trained farmers. Most trained farmers showed higher levels of knowledge of
      pesticide use, higher levels of beliefs in pesticide hazard control, and higher
      levels of safety behavior than non-trained farmers. Knowledge of pesticide use
      and beliefs regarding pesticide hazard control were significantly correlated with
      safety behavior in both groups of farmers. Concerning farmers' beliefs regarding
      pesticide hazard control, trained farmers were more likely to think that safety
      precautions work very well and less likely to feel they had little control over
      avoiding pesticide hazards. Overall, previous training was associated with
      increased levels of farmers' knowledge of pesticides and beliefs about pesticide
      hazard control, was accompanied by elevated safety behavior in farmers, and thus
      was connected with lower occupational exposure to pesticides. Interventions that
      facilitate knowledge and compliance with safety behaviors should become a
      priority for decreasing exposure to pesticides among farmers.

PMID- 29051452
TI  - Metal Levels in Blood of Three Species of Shorebirds during Stopover on Delaware
      Bay Reflect Levels in Their Food, Horseshoe Crab Eggs.
AB  - Understanding the relationship between metal level in predators and their prey is
      an important issue, and is usually difficult to determine because animals eat a
      variety of organisms. However, shorebirds that stop over during spring migration
      along Delaware Bay (New Jersey) stay for only 2-3 weeks, and eat mainly horseshoe
      crab (Limulus polyphemus) eggs. In this paper, we examine the relationship
      between metal levels in horseshoe crab eggs, and blood and feather levels of
      metals in red knot (Calidris canutus rufa; n = 30), sanderling (Calidris alba; n
      = 20) and semipalmated sandpiper (Calidris pusilla; n = 38) from Delaware Bay.
      There is a rich literature on metal levels in feathers. For all three species,
      the levels of arsenic, cadmium, chromium, lead and mercury in blood were highly
      correlated with the levels of metals in the eggs of horseshoe crab (17 pooled
      samples). This indicates that the levels in the blood of these shorebirds quickly
      reflect levels in their prey (horseshoe crab eggs), while metals in the feathers
      were not correlated with the levels in eggs. Semipalmated sandpipers had the
      lowest levels of arsenic in blood and the highest levels of arsenic in feathers,
      compared to the other species. At Delaware Bay, semipalmated sandpipers have a
      diet higher in marsh invertebrates than the other species, which may account for
      the differences. The levels of cadmium and chromium in blood were significantly
      higher in knots than other species; knots only ate horseshoe crab eggs. For all
      of the metals except arsenic, the ratio of levels in blood/feathers was similar
      among species. For arsenic, the ratio of levels in blood/feathers were
      significantly lower in semipalmated sandpipers than in the other species, by an
      order of magnitude.

PMID- 29051453
TI  - A Retrospective Analysis of Agricultural Herbicides in Surface Water Reveals Risk
      Plausibility for Declines in Submerged Aquatic Vegetation.
AB  - The Albemarle-Pamlico Estuarine System (APES) is the second largest estuarine
      system within the mainland of the United States and is estimated to have lost
      about half of its submerged aquatic vegetation (SAV) over the past several
      decades. The issue of herbicide runoff and subsequent toxic effects to SAV is
      important because of the extensive agricultural production that occurs in the
      APES region. The aim of this study was to conduct a retrospective analysis of
      herbicide influx to waters of the APES region during the time period of
      documented SAV declines and to compare the measured concentrations to SAV
      toxicity thresholds and changes in agricultural land use. Surface water grab
      samples were collected at 26 sites in the APES region during May through July
      2000. The most consistently measured herbicides were alachlor, atrazine, and
      metolachlor with geometric mean concentrations ranging from 29 to 2463 ng/L for
      alachlor, 14 to 7171 ng/L for atrazine, and 17 to 5866 ng/L for metolachlor.
      Concentrations of alachlor, atrazine, and metolachlor measured in water samples
      from the APES region in 2000 exceeded several of the established benchmarks,
      standards, or guidelines for protection of aquatic plants. Although this
      evaluation was of point-in-time herbicide samples (year 2000) and not analyzed
      for all possible herbicides used at the time, they were taken during the period
      of SAV declines, reveal the plausibility of exposure risk to SAV, and suggest
      that herbicide runoff should be studied along with other variables that influence
      SAV growth and distribution in future studies.

PMID- 29051455
TI  - Fate of Chloromethanes in the Atmospheric Environment: Implications for Human
      Health, Ozone Formation and Depletion, and Global Warming Impacts.
AB  - Among the halogenated hydrocarbons, chloromethanes (i.e., methyl chloride, CH3Cl;
      methylene chloride, CH2Cl2; chloroform, CHCl3; and carbon tetrachloride, CCl4)
      play a vital role due to their extensive uses as solvents and chemical
      intermediates. This article aims to review their main chemical/physical
      properties and commercial/industrial uses, as well as the environment and health
      hazards posed by them and their toxic decomposition products. The environmental
      properties (including atmospheric lifetime, radiative efficiency, ozone depletion
      potential, global warming potential, photochemical ozone creation potential, and
      surface mixing ratio) of these chlorinated methanes are also reviewed. In
      addition, this paper further discusses their atmospheric fates and human health
      implications because they are apt to reside in the lower atmosphere when released
      into the environment. According to the atmospheric degradation mechanism, their
      toxic degradation products in the troposphere include hydrogen chloride (HCl),
      carbon monoxide (CO), chlorine (Cl2), formyl chloride (HCOCl), carbonyl chloride
      (COCl2), and hydrogen peroxide (H2O2). Among them, COCl2 (also called phosgene)
      is a powerful irritating gas, which is easily hydrolyzed or thermally decomposed
      to form hydrogen chloride.

PMID- 29051454
TI  - Occupational Exposure to Bisphenol A (BPA): A Reality That Still Needs to Be
      Unveiled.
AB  - Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, is one of the most utilized
      industrial chemicals worldwide, with the ability to interfere with/or mimic
      estrogenic hormones with associated biological responses. Environmental human
      exposure to this endocrine disruptor, mostly through oral intake, is considered a
      generalized phenomenon, particularly in developed countries. However, in the
      context of occupational exposure, non-dietary exposure sources (e.g., air and
      contact) cannot be underestimated. Here, we performed a review of the literature
      on BPA occupational exposure and associated health effects. Relevantly, the
      authors only identified 19 studies from 2009 to 2017 that demonstrate that
      occupationally exposed individuals have significantly higher detected BPA levels
      than environmentally exposed populations and that the detection rate of serum BPA
      increases in relation to the time of exposure. However, only 12 studies performed
      in China have correlated potential health effects with detected BPA levels, and
      shown that BPA-exposed male workers are at greater risk of male sexual
      dysfunction across all domains of sexual function; also, endocrine disruption,
      alterations to epigenetic marks (DNA methylation) and epidemiological evidence
      have shown significant effects on the offspring of parents exposed to BPA during
      pregnancy. This overview raises awareness of the dramatic and consistent increase
      in the production and exposure of BPA and creates urgency to assess the actual
      exposure of workers to this xenoestrogen and to evaluate potential associated
      adverse health effects.

PMID- 29051456
TI  - Self-Reported Symptoms and Pesticide Use among Farm Workers in Arusha, Northern
      Tanzania: A Cross Sectional Study.
AB  - The objective of the study was to describe self-reported health symptoms, the use
      of personal protective gear and clothing and poor safety procedures when applying
      pesticides among farm workers. A total of 128 adult farm workers were interviewed
      using a structured questionnaire during the farming season. The commonly used
      pesticides included profenofos, mancozeb, chlorpyrifos, cypermethrin,
      deltamethrin, permethrin, lambda-cyhalothrin, endosulfan and carbosulfan. The
      majority (>90%) of farm workers used no personal protective clothing while
      handling pesticides. More than one-third of farm workers ate and drank without
      washing their hands following pesticide handling, while a smaller number smoked
      or chewed gum. Wearing special boots during pesticide application was found to
      reduce the risk of skin rash (OR = 0.2, 95% CI: 0.06-0.66), whereas smoking when
      applying pesticides increased the risk of chest pain occurrence (OR = 4.0, 95%
      CI: 1.14-15.43), as well as forgetfulness (OR = 4.0, 95% CI: 1.30-14.02). Chewing
      gum and eating when applying pesticides was associated with diarrhoea (OR = 11.0,
      95% CI: 1.80-6.84 and OR = 7.0, 95% CI: 1.27-3.67 respectively). The increased
      self-reported prevalence of post-exposure adverse health effects among farm
      workers was associated with poor use of personal protective clothing and poor
      safety practices during pesticide use and handling. These data indicate the need
      for improved availability and use of protective equipment, and training in crop
      and pest management practices to prevent risky behavioursand for safer and
      sustainable vegetable production.

PMID- 29051457
TI  - Hydrophobic Sand Is a Non-Toxic Method of Urine Collection, Appropriate for
      Urinary Metal Analysis in the Rat.
AB  - Hydrophobic sand is a relatively new method of urine collection in the rodent,
      comparable to the established method using a metabolic cage. Urine samples are
      often used in rodent research, especially for biomarkers of health changes after
      internal contamination from embedded metals, such as in a model of a military
      shrapnel wound. However, little research has been done on the potential
      interference of hydrophobic sand with urine metal concentrations either by
      contamination from the sand particulate, or adsorption of metals from the urine.
      We compare urine collected from rats using the metabolic cage method and the
      hydrophobic sand method for differences in metal concentration of common urinary
      metals, and examine physical properties of the sand material for potential
      sources of contamination. We found minimal risk of internal contamination of the
      rat by hydrophobic sand, and no interference of the sand with several common
      metals of interest (cobalt, strontium, copper, and manganese), although we advise
      caution in studies of aluminum in urine.

PMID- 29051458
TI  - Heavy Metal Pollution of Chari River Water during the Crossing of N'Djamena
      (Chad).
AB  - This study was carried out to identify and assess the water quality of the Chari
      River. The Chari, 1200 km long, is Chad's major water source. Municipal sewage,
      industrial wastewater discharge, and seasonal run-off from agriculture are
      regularly fed into the river. Several trace metals such as Cu, Zn, Fe, Ni, Cr,
      Mn, and Cd, were measured in different sampling stations located along the Chari
      River at N'Djamena in different campaigns from 2008 to 2010. Overall, manganese,
      zinc, chromium, and copper concentration levels were mainly in the range of the
      permissible limits prescribed by WHO guidelines (WHO 2011). Nickel, iron, and
      cadmium concentrations were still high. This preliminary study allowed us to
      identify the magnitude of toxic pollutants, which are responsible for Chari River
      water contamination in the study area. This study revealed that urgent measures
      must be taken to protect the local people from health problems resulting from
      high concentrations of heavy metals.

PMID- 29051459
TI  - High Risk Subgroups Sensitive to Air Pollution Levels Following an Emergency
      Medical Admission.
AB  - For three cohorts (the elderly, socially deprived, and those with chronic
      disabling disease), the relationship between the concentrations of particulate
      matter (PM10), sulphur dioxide (SO2), or oxides of nitrogen (NOx) at the time of
      hospital admission and outcomes (30-day in-hospital mortality) were investigated
      All emergency admissions (90,423 episodes, recorded in 48,035 patients) between
      2002 and 2015 were examined. PM10, SO2, and NOx daily levels from the hospital
      catchment area were correlated with the outcomes for the older admission cohort
      (>70 years), those of lower socio-economic status (SES), and with more disabling
      disease. Adjusted for acuity and complexity, the level of each pollutant on the
      day of admission independently predicted the 30-day mortality: for PM10-OR 1.11
      (95% CI: 1.08, 1.15), SO2-1.20 (95% CI: 1.16, 1.24), and NOx-1.09 (1.06-1.13).
      For the older admission cohort (>=70 years), as admission day pollution increased
      (NOx quintiles) the 30-day mortality was higher in the elderly (14.2% vs. 11.3%:
      p < 0.001). Persons with a lower SES were at increased risk. Persons with more
      disabling disease also had worse outcomes on days with higher admission
      particulate matter (PM10 quintiles). Levels of pollutants on the day of admission
      of emergency medical admissions predicted 30-day hospital mortality.

PMID- 29051460
TI  - Changes in the Treatment of Some Physico-Chemical Properties of Cassava Mill
      Effluents Using Saccharomyces cerevisiae.
AB  - Cassava is majorly processed into gari by smallholders in Southern Nigeria.
      During processing, large volume of effluents are produced in the pressing stage
      of cassava tuber processing. The cassava mill effluents are discharged into the
      soil directly and it drain into nearby pits, surface water, and canals without
      treatment. Cassava mill effluents is known to alter the receiving soil and water
      characteristics and affects the biota in such environments, such as fishes
      (water), domestic animals, and vegetation (soil). This study investigated the
      potential of Saccharomyces cerevisiae to be used for the treatment of some
      physicochemical properties of cassava mill effluents. S. cerevisiae was isolated
      from palm wine and identified based on conventional microbiological techniques,
      viz. morphological, cultural, and physiological/biochemical characteristics. The
      S. cerevisiae was inoculated into sterile cassava mill effluents and incubated
      for 15 days. Triplicate samples were withdrawn from the setup after the fifth day
      of treatment. Portable equipment was used to analyze the in-situ parameters, viz.
      total dissolved solids (TDS), pH, dissolved oxygen (DO), conductivity, salinity,
      and turbidity. Anions (nitrate, sulphate, and phosphate) and chemical oxygen
      demand (COD) were analyzed using spectrophotometric and open reflux methods
      respectively. Results showed a decline of 37.62%, 22.96%, 29.63%, 20.49%, 21.44%,
      1.70%, 53.48%, 68.00%, 100%, and 74.48% in pH, conductivity, DO, TDS, salinity,
      sulphate, nitrate, phosphate, and COD levels respectively, and elevation of
      17.17% by turbidity. The study showed that S. cerevisiae could be used for the
      treatment of cassava mill effluents prior to being discharged into the
      environment so as to reduce the pollution or contamination and toxicity levels.

PMID- 29051462
TI  - Modeling Short-Term Maximum Individual Exposure from Airborne Hazardous Releases
      in Urban Environments. Part I: Validation of a Deterministic Model with Field
      Experimental Data.
AB  - The release of airborne hazardous substances in the atmosphere has a direct
      effect on human health as, during the inhalation, an amount of concentration is
      inserted through the respiratory system into the human body, which can cause
      serious or even irreparable damage in health. One of the key problems in such
      cases is the prediction of the maximum individual exposure. Current state of the
      art methods, which are based on the concentration cumulative distribution
      function and require the knowledge of the concentration variance and the
      intermittency factor, have limitations. Recently, authors proposed a
      deterministic approach relating maximum individual exposure to parameters such as
      the fluctuation intensity and the concentration integral time scale. The purpose
      of the first part of this study is to validate the deterministic approach with
      the extensive dataset of the MUST (Mock Urban Setting Test) field experiment.
      This dataset includes 81 trials, which practically cover various atmospheric
      conditions and stability classes and contains in total 4004 non-zero
      concentration sensor data with time resolutions of 0.01-0.02 s. The results
      strengthen the usefulness of the deterministic model in predicting short-term
      maximum individual exposure. Another important output is the estimation of the
      methodology uncertainty involved.

PMID- 29051461
TI  - Exposure to Inorganic Nanoparticles: Routes of Entry, Immune Response,
      Biodistribution and In Vitro/In Vivo Toxicity Evaluation.
AB  - The development of different kinds of nanoparticles, showing different physico
      chemical properties, has fostered their large use in many fields, including
      medicine. As a consequence, inorganic nanoparticles (e.g., metals or
      semiconductors), have raised issues about their potential toxicity. The
      scientific community is investigating the toxicity mechanisms of these materials,
      in vitro and in vivo, in order to provide accurate references concerning their
      use. This review will give the readers a thorough exploration on the entry
      mechanisms of inorganic nanoparticles in the human body, such as titanium dioxide
      nanoparticles (TiO2NPs), silicon dioxide nanoparticles (SiO2NPs), zinc oxide
      nanoparticles (ZnONPs), silver nanoparticles (AgNPs), gold nanoparticles (AuNPs)
      and quantum dots (QDsNPs). In addition, biodistribution, the current trends and
      novelties of in vitro and in vivo toxicology studies will be discussed, with a
      particular focus on immune response.

PMID- 29051463
TI  - Modelling Short-Term Maximum Individual Exposure from Airborne Hazardous Releases
      in Urban Environments. Part IotaI: Validation of a Deterministic Model with Wind
      Tunnel Experimental Data.
AB  - The capability to predict short-term maximum individual exposure is very
      important for several applications including, for example, deliberate/accidental
      release of hazardous substances, odour fluctuations or material flammability
      level exceedance. Recently, authors have proposed a simple approach relating
      maximum individual exposure to parameters such as the fluctuation intensity and
      the concentration integral time scale. In the first part of this study (Part I),
      the methodology was validated against field measurements, which are governed by
      the natural variability of atmospheric boundary conditions. In Part II of this
      study, an in-depth validation of the approach is performed using reference data
      recorded under truly stationary and well documented flow conditions. For this
      reason, a boundary-layer wind-tunnel experiment was used. The experimental
      dataset includes 196 time-resolved concentration measurements which detect the
      dispersion from a continuous point source within an urban model of semi-idealized
      complexity. The data analysis allowed the improvement of an important model
      parameter. The model performed very well in predicting the maximum individual
      exposure, presenting a factor of two of observations equal to 95%. For large time
      intervals, an exponential correction term has been introduced in the model based
      on the experimental observations. The new model is capable of predicting all time
      intervals giving an overall factor of two of observations equal to 100%.

PMID- 29051465
TI  - An Overview of Bortezomib-Induced Neurotoxicity.
AB  - The boronic acid dipeptide bortezomib, able to induce tumor cell death by
      degradation of key proteins, is the first proteasome inhibitor drug to enter
      clinical practice. It is employed as first-line treatment in relapsed or
      resistant multiple myeloma (MM) patients. However, bortezomib often induces a
      dose-limiting toxicity in the form of painful sensory neuropathy, which can
      mainly be reduced by subcutaneous administration or dose modification. In this
      review we focus on the current understanding of the pathophysiological mechanisms
      of bortezomib-induced neuropathy to allow further studies in animal models and
      humans, including analysis of clinical and pharmacogenetic aspects, to optimize
      the treatment regimens.

PMID- 29051464
TI  - Cisplatin-Induced Ototoxicity: Effects, Mechanisms and Protection Strategies.
AB  - Cisplatin is a highly effective chemotherapeutic agent that is widely used to
      treat solid organ malignancies. However, serious side effects have been
      associated with its use, such as bilateral, progressive, irreversible, dose
      dependent neurosensory hearing loss. Current evidence indicates that cisplatin
      triggers the production of reactive oxygen species in target tissues in the inner
      ear. A variety of agents that protect against cisplatin-induced ototoxicity have
      been successfully tested in cell culture and animal models. However, many of them
      interfere with the therapeutic effect of cisplatin, and therefore are not
      suitable for systemic administration in clinical practice. Consequently, local
      administration strategies, namely intratympanic administration, have been
      developed to achieve otoprotection, without reducing the antitumoral effect of
      cisplatin. While a considerable amount of pre-clinical information is available,
      clinical data on treatments to prevent cisplatin ototoxicity are only just
      beginning to appear. This review summarizes clinical and experimental studies of
      cisplatin ototoxicity, and focuses on understanding its toxicity mechanisms,
      clinical repercussions and prevention strategies.

PMID- 29051466
TI  - Current View in Platinum Drug Mechanisms of Peripheral Neurotoxicity.
AB  - Peripheral neurotoxicity is the dose-limiting factor for clinical use of platinum
      derivatives, a class of anticancer drugs which includes cisplatin, carboplatin,
      and oxaliplatin. In particular cisplatin and oxaliplatin induce a severe
      peripheral neurotoxicity while carboplatin is less neurotoxic. The mechanisms
      proposed to explain these drugs' neurotoxicity are dorsal root ganglia
      alteration, oxidative stress involvement, and mitochondrial dysfunction.
      Oxaliplatin also causes an acute and reversible neuropathy, supposed to be due by
      transient dysfunction of the voltage-gated sodium channels of sensory neurons.
      Recent studies suggest that individual genetic variation may play a role in the
      pathogenesis of platinum drug neurotoxicity. Even though all these mechanisms
      have been investigated, the pathogenesis is far from clearly defined. In this
      review we will summarize the current knowledge and the most up-to-date hypotheses
      on the mechanisms of platinum drug-induced peripheral neurotoxicity.

PMID- 29051469
TI  - Current State of Developmental Neurotoxicology Research.
AB  - We have been witness to significant research advances in areas such as
      neuroscience, neurodegeneration, cancer therapy, etc., yet, investigation in
      developmental neurotoxicology (DNT) has fallen behind [1]. [...].

PMID- 29051468
TI  - Additivity and Interactions in Ecotoxicity of Pollutant Mixtures: Some Patterns,
      Conclusions, and Open Questions.
AB  - Understanding the effects of exposure to chemical mixtures is a common goal of
      pharmacology and ecotoxicology. In risk assessment-oriented ecotoxicology,
      defining the scope of application of additivity models has received utmost
      attention in the last 20 years, since they potentially allow one to predict the
      effect of any chemical mixture relying on individual chemical information only.
      The gold standard for additivity in ecotoxicology has demonstrated to be Loewe
      additivity which originated the so-called Concentration Addition (CA) additivity
      model. In pharmacology, the search for interactions or deviations from additivity
      (synergism and antagonism) has similarly captured the attention of researchers
      over the last 20 years and has resulted in the definition and application of the
      Combination Index (CI) Theorem. CI is based on Loewe additivity, but focused on
      the identification and quantification of synergism and antagonism. Despite
      additive models demonstrating a surprisingly good predictive power in chemical
      mixture risk assessment, concerns still exist due to the occurrence of
      unpredictable synergism or antagonism in certain experimental situations. In the
      present work, we summarize the parallel history of development of CA, IA, and CI
      models. We also summarize the applicability of these concepts in ecotoxicology
      and how their information may be integrated, as well as the possibility of
      prediction of synergism. Inside the box, the main question remaining is whether
      it is worthy to consider departures from additivity in mixture risk assessment
      and how to predict interactions among certain mixture components. Outside the
      box, the main question is whether the results observed under the experimental
      constraints imposed by fractional approaches are a de fide reflection of what it
      would be expected from chemical mixtures in real world circumstances.

PMID- 29051467
TI  - Axonal Transport Impairment in Chemotherapy-Induced Peripheral Neuropathy.
AB  - Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting side effect
      of several antineoplastic drugs which significantly reduces patients' quality of
      life. Although different molecular mechanisms have been investigated, CIPN
      pathobiology has not been clarified yet. It has largely been recognized that
      Dorsal Root Ganglia are the main targets of chemotherapy and that the longest
      nerves are the most damaged, together with fast axonal transport. Indeed, this
      bidirectional cargo-specific transport has a pivotal role in neuronal function
      and its impairment is involved in several neurodegenerative and
      neurodevelopmental diseases. Literature data demonstrate that, despite different
      mechanisms of action, all antineoplastic agents impair the axonal trafficking to
      some extent and the severity of the neuropathy correlates with the degree of
      damage on this bidirectional transport. In this paper, we will examine the effect
      of the main old and new chemotherapeutic drug categories on axonal transport,
      with the aim of clarifying their potential mechanisms of action, and, if
      possible, of identifying neuroprotective strategies, based on the knowledge of
      the alterations induced by each drugs.

PMID- 29051470
TI  - Hepatotoxicity, Nephrotoxicity and Oxidative Stress in Rat Testis Following
      Exposure to Haloxyfop-p-methyl Ester, an Aryloxyphenoxypropionate Herbicide.
AB  - Haloxyfop-p-methyl ester (HPME) ((R)-2-{4-[3-chloro-5-(trifluoromethyl)-2
      pyridyloxy]phenoxy}propionic acid), is a selective aryloxyphenoxypropionate
      (AOPP) herbicide. It exerts phytotoxicity through inhibition of lipid metabolism
      and induction of oxidative stress in susceptible plants. This study investigated
      the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170
      210 g) were randomized into four groups (I-IV). Group I (control) received 1 mL
      of distilled water, while animals in Groups II, III and IV received 6.75, 13.5
      and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant
      (p < 0.05) increase in renal and hepatic function biomarkers (urea, creatinine,
      total bilirubin, ALP, ALT, AST) in the plasma of treated animals compared to
      control. Levels of testicular antioxidants, ascorbic acid and glutathione, and
      activities of glutathione-S-transferase, superoxide dismutase and catalase were
      reduced significantly after 21 days of HPME administration in a dose-dependent
      manner. The testicular malondialdehyde level increased significantly in the HPME
      treated rats relative to the control. A significant decrease in testicular
      lactate dehydrogenase, acid phosphatase and gamma-glutamyl transferase was also
      observed in HPME-treated animals. Testicular histology revealed severe
      interstitial edema and sections of seminiferous tubules with necrotic and eroded
      germinal epithelium in the HPME-treated rats. Overall, data from this study
      suggest that HPME altered hepatic and renal function and induced oxidative stress
      and morphological changes in the testis of rats.

PMID- 29051472
TI  - Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global
      DNA Methylation and in Nurr1 Gene Expression.
AB  - Environmental exposure to pesticides during the early stages of development
      represents an important risk factor for the onset of neurodegenerative diseases
      in adult age. Neonatal exposure to Permethrin (PERM), a member of the family of
      synthetic pyrethroids, can induce a Parkinson-like disease and cause some
      alterations in striatum of rats, involving both genetic and epigenetic pathways.
      Through gene expression analysis and global DNA methylation assessment in both
      PERM-treated parents and their untreated offspring, we investigated on the
      prospective intergenerational effect of this pesticide. Thirty-three percent of
      progeny presents the same Nurr1 alteration as rats exposed to permethrin in early
      life. A decrease in global genome-wide DNA methylation was measured in mothers
      exposed in early life to permethrin as well as in their offspring, whereas
      untreated rats have a hypermethylated genomic DNA. Further studies are however
      needed to elucidate the molecular mechanisms, but, despite this, an
      intergenerational PERM-induced damage on progenies has been identified for the
      first time.

PMID- 29051471
TI  - Nanotoxicology and Metalloestrogens: Possible Involvement in Breast Cancer.
AB  - As the use of nanotechnology has expanded, an increased number of metallic oxides
      have been manufactured, yet toxicology testing has lagged significantly. Metals
      used in nano-products include titanium, silicon, aluminum, silver, zinc, cadmium,
      cobalt, antimony, gold, etc. Even the noble metals, platinum and cerium, have
      been used as a treatment for cancer, but the toxicity of these metals is still
      unknown. Significant advances have been made in our understanding and treatment
      of breast cancer, yet millions of women will experience invasive breast cancer in
      their lifetime. The pathogenesis of breast cancer can involve multiple factors;
      (1) genetic; (2) environmental; and (3) lifestyle-related factors. This review
      focuses on exposure to highly toxic metals, ("metalloestrogens" or "endocrine
      disruptors") that are used as the metallic foundation for nanoparticle production
      and are found in a variety of consumer products such as cosmetics, household
      items, and processed foods, etc. The linkage between well-understood
      metalloestrogens such as cadmium, the use of these metals in the production of
      nanoparticles, and the relationship between their potential estrogenic effects
      and the development of breast cancer will be explored. This will underscore the
      need for additional testing of materials used in nano-products. Clearly, a
      significant amount of work needs to be done to further our understanding of these
      metals and their potential role in the pathogenesis of breast cancer.

PMID- 29051473
TI  - Glyphosate in Runoff Waters and in the Root-Zone: A Review.
AB  - Glyphosate is the most commonly-used herbicide in the world. The present review
      summarizes the discovery, prevalence, chemical and physical properties, mode of
      action and effects in plants, glyphosate resistance and the environmental fate of
      glyphosate. Numerous studies are reviewed that demonstrate that glyphosate may
      run off of fields where it is applied, while other studies provide evidence that
      plant roots can take up glyphosate. Non-target vegetation may be exposed to
      glyphosate in the root-zone, where it has the potential to remove aqueous
      glyphosate from the system. Further study on the effects of root-zone glyphosate
      on non-target vegetation is required to develop best management practices for
      land managers seeking to ameliorate the effects of root-zone glyphosate exposure.

PMID- 29051474
TI  - The Role of the Component Metals in the Toxicity of Military-Grade Tungsten
      Alloy.
AB  - Tungsten-based composites have been recommended as a suitable replacement for
      depleted uranium. Unfortunately, one of these mixtures composed of tungsten (W),
      nickel (Ni) and cobalt (Co) induced rhabdomyosarcomas when implanted into the leg
      muscle of laboratory rats and mice to simulate a shrapnel wound. The question
      arose as to whether the neoplastic effect of the mixture could be solely
      attributed to one or more of the metal components. To investigate this
      possibility, pellets with one or two of the component metals replaced with an
      identical amount of the biologically-inert metal tantalum (Ta) were manufactured
      and implanted into the quadriceps of B6C3F1 mice. The mice were followed for two
      years to assess potential adverse health effects. Implantation with WTa, CoTa or
      WNiTa resulted in decreased survival, but not to the level reported for WNiCo.
      Sarcomas in the implanted muscle were found in 20% of the CoTa-implanted mice and
      5% of the WTa- and WCoTa-implanted rats and mice, far below the 80% reported for
      WNiCo-implanted mice. The data obtained from this study suggested that no single
      metal is solely responsible for the neoplastic effects of WNiCo and that a
      synergistic effect of the three metals in tumor development was likely.

PMID- 29051476
TI  - Independent Factors Predicting Postoperative 30-Day Mortality in 101 Infants
      Following Liver Transplantation.
AB  - BACKGROUND Liver transplantation (LT) in infants is a challenging procedure. This
      study was designed to identify risk factors of 30-day mortality of infant LT
      recipients. MATERIAL AND METHODS A total of 101 infants treated between May 1997
      and March 2015 were assigned to one of two groups, a deceased infant group (n=9)
      or a live infant group (n=92), according to their mortality status at 30 days
      after LT. RESULTS Patient characteristics of height, weight, preoperative total
      bilirubin, creatinine clearance, primary diagnosis, and graft-to-recipient weight
      ratio (GRWR) were significantly different between the two groups. In a binary
      logistic regression model for multivariate analysis, independent predictors of
      postoperative mortality in infants after LT were hospitalization in the intensive
      care unit before LT, reoperation within 30 days of the first operation, and high
      GRWR (>4). CONCLUSIONS Postoperative mortality of infants following LT showed
      significant correlations with recipient preoperative and postoperative conditions
      and also with graft size mismatch. Regarding GRWR, our data indicated that
      relatively large grafts given to infant recipients often lead to graft failure or
      primary nonfunction during the postoperative stage.

PMID- 29051475
TI  - Foreign Body Ingestion Causing Recurrent Diverticulitis.
AB  - BACKGROUND Ingested foreign bodies (IFBs) are usually asymptomatic and are
      excreted uneventfully. IFBs become a major concern in elderly patients due to the
      increase number of diverticuloses where the foreign body can lodge and cause
      severe complications. CASE REPORT We report a case of an elderly patient who
      ingested a chicken bone that caused recurrent diverticulitis. CONCLUSIONS The
      diagnosis of complicated IFB cases is challenging, requires physician clinical
      expertise, and must be considered in individuals at risk.

PMID- 29051477
TI  - Low kV and Low Concentration Contrast Agent with Iterative Reconstruction of
      Computed Tomography (CT) Coronary Angiography: A Preliminary Study.
AB  - BACKGROUND The aim of this study was to evaluate the image quality and radiation
      dose of CT coronary angiography (CTCA) with low kV, low concentration contrast
      agent, and iterative reconstruction. MATERIAL AND METHODS Ninety cases were
      randomly divided into 3 groups according to contrast agent concentration: group A
      270 mg/ml (100 kV), group B 350 mg/ml (120 kV), and group C 370 mg/ml (120 kV),
      with 30 cases per group. Tube current was 200-250 mAs. Collimator width was
      128*0.6 mm. Rotation speed was 0.27 s. The CT value of the left and right
      coronary arteries and the ascending aortic root was measured. The SNR and CNR of
      the images were calculated to evaluate the image quality objectively. The CTDI,
      DLP, and contrast injection were recorded. RESULTS There were no significant
      differences in sex, age, weight, height, and BMI among the 3 groups. There was no
      statistically significant difference between left and right coronary artery and
      ascending aortic root CT value, background noise, SNR, and CNR. Compared to B and
      C, the ED in group A decreased by about 27.58% and 28.21%, respectively. The
      total amount of iodine in group A was decreased by about 21.27% and 24.83%,
      respectively compared with groups B and C. CONCLUSIONS Low kV and low
      concentration contrast agent combined with iterative reconstruction for CTCA
      imaging produced image quality consistent with that of conventional CTCA and
      significantly reduced the dosage of the radiation and injected iodine.

PMID- 29051478
TI  - Genetic accommodation via modified endocrine signalling explains phenotypic
      divergence among spadefoot toad species.
AB  - Phenotypic differences among species may evolve through genetic accommodation,
      but mechanisms accounting for this process are poorly understood. Here we compare
      hormonal variation underlying differences in the timing of metamorphosis among
      three spadefoot toads with different larval periods and responsiveness to pond
      drying. We find that, in response to pond drying, Pelobates cultripes and Spea
      multiplicata accelerate metamorphosis, increase standard metabolic rate (SMR),
      and elevate whole-body content of thyroid hormone (the primary morphogen
      controlling metamorphosis) and corticosterone (a stress hormone acting
      synergistically with thyroid hormone to accelerate metamorphosis). In contrast,
      Scaphiopus couchii has the shortest larval period, highest whole-body thyroid
      hormone and corticosterone content, and highest SMR, and these trait values are
      least affected by pond drying among the three species. Our findings support that
      the atypically rapid and canalized development of S. couchii evolved by genetic
      accommodation of endocrine pathways controlling metamorphosis, showing how
      phenotypic plasticity within species may evolve into trait variation among
      species.

PMID- 29051479
TI  - Spin crossover-induced colossal positive and negative thermal expansion in a
      nanoporous coordination framework material.
AB  - External control over the mechanical function of materials is paramount in the
      development of nanoscale machines. Yet, exploiting changes in atomic behaviour to
      produce controlled scalable motion is a formidable challenge. Here, we present an
      ultra-flexible coordination framework material in which a cooperative electronic
      transition induces an extreme abrupt change in the crystal lattice conformation.
      This arises due to a change in the preferred coordination character of Fe(II)
      sites at different spin states, generating scissor-type flexing of the crystal
      lattice. Diluting the framework with transition-inactive Ni(II) sites disrupts
      long-range communication of spin state through the lattice, producing a more
      gradual transition and continuous lattice movement, thus generating colossal
      positive and negative linear thermal expansion behaviour, with coefficients of
      thermal expansion an order of magnitude greater than previously reported. This
      study has wider implications in the development of advanced responsive
      structures, demonstrating electronic control over mechanical motion.

PMID- 29051480
TI  - NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic
      reprogramming to drug resistance.
AB  - The molecular mechanisms that couple glycolysis to cancer drug resistance remain
      unclear. Here we identify an ATP-binding motif within the NADPH oxidase isoform,
      NOX4, and show that ATP directly binds and negatively regulates NOX4 activity. We
      find that NOX4 localizes to the inner mitochondria membrane and that subcellular
      redistribution of ATP levels from the mitochondria act as an allosteric switch to
      activate NOX4. We provide evidence that NOX4-derived reactive oxygen species
      (ROS) inhibits P300/CBP-associated factor (PCAF)-dependent acetylation and
      lysosomal degradation of the pyruvate kinase-M2 isoform (PKM2). Finally, we show
      that NOX4 silencing, through PKM2, sensitizes cultured and ex vivo freshly
      isolated human-renal carcinoma cells to drug-induced cell death in xenograft
      models and ex vivo cultures. These findings highlight yet unidentified insights
      into the molecular events driving cancer evasive resistance and suggest
      modulation of ATP levels together with cytotoxic drugs could overcome drug
      resistance in glycolytic cancers.

PMID- 29051481
TI  - Genome-wide prediction of DNase I hypersensitivity using gene expression.
AB  - We evaluate the feasibility of using a biological sample's transcriptome to
      predict its genome-wide regulatory element activities measured by DNase I
      hypersensitivity (DH). We develop BIRD, Big Data Regression for predicting DH, to
      handle this high-dimensional problem. Applying BIRD to the Encyclopedia of DNA
      Elements (ENCODE) data, we found that to a large extent gene expression predicts
      DH, and information useful for prediction is contained in the whole transcriptome
      rather than limited to a regulatory element's neighboring genes. We show
      applications of BIRD-predicted DH in predicting transcription factor-binding
      sites (TFBSs), turning publicly available gene expression samples in Gene
      Expression Omnibus (GEO) into a regulome database, predicting differential
      regulatory element activities, and facilitating regulome data analyses by serving
      as pseudo-replicates. Besides improving our understanding of the regulome
      transcriptome relationship, this study suggests that transcriptome-based
      prediction can provide a useful new approach for regulome mapping.

PMID- 29051482
TI  - Bidirectional wavelength-division multiplexing transmission over installed fibre
      using a simplified optical coherent access transceiver.
AB  - High-speed broadband services require optical fibres in access networks, in which
      multiple subscribers are connected to service providers, to satisfy the
      continuously growing bandwidth demand. The primitive signaling scheme used in
      access networks enables the use of low-cost equipment but diminishes the
      bandwidth available to end-users. Thus, current technology will be unable to
      support future broadband demands. Coherent communication systems offer
      significantly improved power- and bandwidth-efficiency, but require fundamental
      simplifications to become economically viable for access networks. Here, we
      demonstrate a promising simplified coherent receiver exhibiting a robust
      performance against polarisation fluctuations over an installed fibre network. It
      enables the realisation of high-order modulation formats and offers high
      sensitivities, achieving a four-fold increase in the supported number of
      subscribers and approximately doubling the transmission distance compared to the
      recently standardized access technology. The proposed solution indicates that
      digital coherent technology can be feasible and transform the access networks,
      enabling ubiquitous new services and applications with uncontended, multi
      gigabits/user broadband connections.

PMID- 29051483
TI  - Ets transcription factor GABP controls T cell homeostasis and immunity.
AB  - Peripheral T cells are maintained in the absence of vigorous stimuli, and respond
      to antigenic stimulation by initiating cell cycle progression and functional
      differentiation. Here we show that depletion of the Ets family transcription
      factor GA-binding protein (GABP) in T cells impairs T-cell homeostasis. In
      addition, GABP is critically required for antigen-stimulated T-cell responses in
      vitro and in vivo. Transcriptome and genome-wide GABP-binding site analyses
      identify GABP direct targets encoding proteins involved in cellular redox balance
      and DNA replication, including the Mcm replicative helicases. These findings show
      that GABP has a nonredundant role in the control of T-cell homeostasis and
      immunity.

PMID- 29051484
TI  - High reactivity of deep biota under anthropogenic CO2 injection into basalt.
AB  - Basalts are recognized as one of the major habitats on Earth, harboring diverse
      and active microbial populations. Inconsistently, this living component is rarely
      considered in engineering operations carried out in these environments. This
      includes carbon capture and storage (CCS) technologies that seek to offset
      anthropogenic CO2 emissions into the atmosphere by burying this greenhouse gas in
      the subsurface. Here, we show that deep ecosystems respond quickly to field
      operations associated with CO2 injections based on a microbiological survey of a
      basaltic CCS site. Acidic CO2-charged groundwater results in a marked decrease
      (by ~ 2.5-4) in microbial richness despite observable blooms of lithoautotrophic
      iron-oxidizing Betaproteobacteria and degraders of aromatic compounds, which
      hence impact the aquifer redox state and the carbon fate. Host-basalt dissolution
      releases nutrients and energy sources, which sustain the growth of autotrophic
      and heterotrophic species whose activities may have consequences on mineral
      storage.

PMID- 29051485
TI  - Topologically frustrated ionisation in a water-ammonia ice mixture.
AB  - Water and ammonia are considered major components of the interiors of the giant
      icy planets and their satellites, which has motivated their exploration under
      high P-T conditions. Exotic forms of these pure ices have been revealed at
      extreme (~megabar) pressures, notably symmetric, ionic, and superionic phases.
      Here we report on an extensive experimental and computational study of the high
      pressure properties of the ammonia monohydrate compound forming from an equimolar
      mixture of water and ammonia. Our experiments demonstrate that relatively mild
      pressure conditions (7.4 GPa at 300 K) are sufficient to transform ammonia
      monohydrate from a prototypical hydrogen-bonded crystal into a form where the
      standard molecular forms of water and ammonia coexist with their ionic
      counterparts, hydroxide (OH-) and ammonium [Formula: see text] ions. Using ab
      initio atomistic simulations, we explain this surprising coexistence of
      neutral/charged species as resulting from a topological frustration between local
      homonuclear and long-ranged heteronuclear ionisation mechanisms.

PMID- 29051486
TI  - The giant protein titin regulates the length of the striated muscle thick
      filament.
AB  - The contractile machinery of heart and skeletal muscles has as an essential
      component the thick filament, comprised of the molecular motor myosin. The thick
      filament is of a precisely controlled length, defining thereby the force level
      that muscles generate and how this force varies with muscle length. It has been
      speculated that the mechanism by which thick filament length is controlled
      involves the giant protein titin, but no conclusive support for this hypothesis
      exists. Here we show that in a mouse model in which we deleted two of titin's C
      zone super-repeats, thick filament length is reduced in cardiac and skeletal
      muscles. In addition, functional studies reveal reduced force generation and a
      dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length
      depends on titin and is critical for maintaining muscle health.

PMID- 29051487
TI  - Contribution of livestock H2S to total sulfur emissions in a region with
      intensive animal production.
AB  - Hydrogen sulfide (H2S) from agricultural sources is generally not included in
      sulfur emission estimates even though H2S is the major sulfur compound emitted
      from livestock production. Here we show that in a country with intensive
      livestock production (Denmark), agriculture constitute the most important sulfur
      source category (~49% of all sources of sulfur dioxide), exceeding both the
      production industry and energy categories. The analysis is based on measurements
      of H2S using proton-transfer-reaction mass spectrometry. National emissions are
      obtained using ammonia as a reference pollutant with the validity of this
      approach documented by the high correlation of ammonia and hydrogen sulfide
      emissions. Finisher pig production is the most comprehensively characterized
      agricultural source of sulfur and is estimated to be the largest source of
      atmospheric sulfur in Denmark. The implication for other locations is discussed
      and the results imply that the understanding and modeling of atmospheric sulfate
      sources should include agricultural H2S.

PMID- 29051488
TI  - Coralgal reef morphology records punctuated sea-level rise during the last
      deglaciation.
AB  - Coralgal reefs preserve the signatures of sea-level fluctuations over Earth's
      history, in particular since the Last Glacial Maximum 20,000 years ago, and are
      used in this study to indicate that punctuated sea-level rise events are more
      common than previously observed during the last deglaciation. Recognizing the
      nature of past sea-level rises (i.e., gradual or stepwise) during deglaciation is
      critical for informing models that predict future vertical behavior of global
      oceans. Here we present high-resolution bathymetric and seismic sonar data sets
      of 10 morphologically similar drowned reefs that grew during the last
      deglaciation and spread 120 km apart along the south Texas shelf edge. Herein,
      six commonly observed terrace levels are interpreted to be generated by several
      punctuated sea-level rise events forcing the reefs to shrink and backstep through
      time. These systematic and common terraces are interpreted to record punctuated
      sea-level rise events over timescales of decades to centuries during the last
      deglaciation, previously recognized only during the late Holocene.

PMID- 29051489
TI  - Genomic landscape associated with potential response to anti-CTLA-4 treatment in
      cancers.
AB  - Immunotherapy has emerged as a promising anti-cancer treatment, however, little
      is known about the genetic characteristics that dictate response to
      immunotherapy. We develop a transcriptional predictor of immunotherapy response
      and assess its prediction in genomic data from ~10,000 human tissues across 30
      different cancer types to estimate the potential response to immunotherapy. The
      integrative analysis reveals two distinct tumor types: the mutator type is
      positively associated with potential response to immunotherapy, whereas the
      chromosome-instable type is negatively associated with it. We identify somatic
      mutations and copy number alterations significantly associated with potential
      response to immunotherapy, in particular treatment with anti-CTLA-4 antibody. Our
      findings suggest that tumors may evolve through two different paths that would
      lead to marked differences in immunotherapy response as well as different
      strategies for evading immune surveillance. Our analysis provides resources to
      facilitate the discovery of predictive biomarkers for immunotherapy that could be
      tested in clinical trials.

PMID- 29051490
TI  - Computational design of small transcription activating RNAs for versatile and
      dynamic gene regulation.
AB  - A longstanding goal of synthetic biology has been the programmable control of
      cellular functions. Central to this is the creation of versatile regulatory
      toolsets that allow for programmable control of gene expression. Of the many
      regulatory molecules available, RNA regulators offer the intriguing possibility
      of de novo design-allowing for the bottom-up molecular-level design of genetic
      control systems. Here we present a computational design approach for the creation
      of a bacterial regulator called Small Transcription Activating RNAs (STARs) and
      create a library of high-performing and orthogonal STARs that achieve up to ~
      9000-fold gene activation. We demonstrate the versatility of these STARs-from
      acting synergistically with existing constitutive and inducible regulators, to
      reprogramming cellular phenotypes and controlling multigene metabolic pathway
      expression. Finally, we combine these new STARs with themselves and CRISPRi
      transcriptional repressors to deliver new types of RNA-based genetic circuitry
      that allow for sophisticated and temporal control of gene expression.

PMID- 29051491
TI  - FAN1 interaction with ubiquitylated PCNA alleviates replication stress and
      preserves genomic integrity independently of BRCA2.
AB  - Interstrand cross-link (ICL) hypersensitivity is a characteristic trait of
      Fanconi anemia (FA). Although FANCD2-associated nuclease 1 (FAN1) contributes to
      ICL repair, FAN1 mutations predispose to karyomegalic interstitial nephritis
      (KIN) and cancer rather than to FA. Thus, the biological role of FAN1 remains
      unclear. Because fork stalling in FAN1-deficient cells causes chromosomal
      instability, we reasoned that the key function of FAN1 might lie in the
      processing of halted replication forks. Here, we show that FAN1 contains a
      previously-uncharacterized PCNA interacting peptide (PIP) motif that, together
      with its ubiquitin-binding zinc finger (UBZ) domain, helps recruit FAN1 to
      ubiquitylated PCNA accumulated at stalled forks. This prevents replication fork
      collapse and controls their progression. Furthermore, we show that FAN1 preserves
      replication fork integrity by a mechanism that is distinct from BRCA2-dependent
      homologous recombination. Thus, targeting FAN1 activities and its interaction
      with ubiquitylated PCNA may offer therapeutic opportunities for treatment of BRCA
      deficient tumors.

PMID- 29051492
TI  - Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers.
AB  - Store-operated calcium entry (SOCE) is a major pathway for calcium ions influx
      into cells and has a critical role in various cell functions. Here we demonstrate
      that calcium-bound calmodulin (Ca2+-CaM) binds to the core region of activated
      STIM1. This interaction facilitates slow Ca2+-dependent inactivation after Orai1
      channel activation by wild-type STIM1 or a constitutively active STIM1 mutant. We
      define the CaM-binding site in STIM1, which is adjacent to the STIM1-Orai1
      coupling region. The binding of Ca2+-CaM to activated STIM1 disrupts the STIM1
      Orai1 complex and also disassembles STIM1 oligomer. Based on these results we
      propose a model for the calcium-bound CaM-regulated deactivation of SOCE.

PMID- 29051493
TI  - Variation in a range of mTOR-related genes associates with intracranial volume
      and intellectual disability.
AB  - De novo mutations in specific mTOR pathway genes cause brain overgrowth in the
      context of intellectual disability (ID). By analyzing 101 mMTOR-related genes in
      a large ID patient cohort and two independent population cohorts, we show that
      these genes modulate brain growth in health and disease. We report the mTOR
      activator gene RHEB as an ID gene that is associated with megalencephaly when
      mutated. Functional testing of mutant RHEB in vertebrate animal models indicates
      pathway hyperactivation with a concomitant increase in cell and head size,
      aberrant neuronal migration, and induction of seizures, concordant with the human
      phenotype. This study reveals that tight control of brain volume is exerted
      through a large community of mTOR-related genes. Human brain volume can be
      altered, by either rare disruptive events causing hyperactivation of the pathway,
      or through the collective effects of common alleles.

PMID- 29051494
TI  - MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by
      suppressing Wnt signaling antagonists.
AB  - MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell
      self-renewal and tumorigenesis. However, the in vivo functions of specific
      microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer
      formation remain poorly understood. Here we show that miR-31 is highly expressed
      in MaSC-enriched mammary basal cell population and in mammary tumors, and is
      regulated by NF-kappaB signaling. We demonstrate that miR-31 promotes mammary
      epithelial proliferation and MaSC expansion at the expense of differentiation in
      vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of
      cancer stem cells, as well as decreases tumor-initiating ability and metastasis
      to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple
      signaling pathways, including Prlr/Stat5, TGFbeta and Wnt/beta-catenin.
      Particularly, it activates Wnt/beta-catenin signaling by directly targeting Wnt
      antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues
      miR31-induced mammary defects. Together, these findings identify miR-31 as the
      key regulator of MaSC activity and breast tumorigenesis.

PMID- 29051495
TI  - The beta20-beta21 of gp120 is a regulatory switch for HIV-1 Env conformational
      transitions.
AB  - The entry of HIV-1 into target cells is mediated by the viral envelope
      glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of
      conformational changes in distant domains that move Env from a functionally
      "closed" State 1 to more "open" conformations, but the molecular mechanisms
      underlying allosteric regulation of these transitions are still elusive. Here, we
      develop chemical probes that block CD4-induced conformational changes in Env and
      use them to identify a potential control switch for Env structural
      rearrangements. We identify the gp120 beta20-beta21 element as a major regulator
      of Env transitions. Several amino acid changes in the beta20-beta21 base lead to
      open Env conformations, recapitulating the structural changes induced by CD4
      binding. These HIV-1 mutants require less CD4 to infect cells and are relatively
      resistant to State 1-preferring broadly neutralizing antibodies. These data
      provide insights into the molecular mechanism and vulnerability of HIV-1 entry.

PMID- 29051496
TI  - Evidence for a task-dependent switch in subthalamo-nigral basal ganglia
      signaling.
AB  - Basal ganglia (BG) can either facilitate or inhibit movement through excitatory
      and inhibitory pathways; however whether these opposing signals are dynamically
      regulated during healthy behavior is not known. Here, we present compelling
      neurophysiological evidence from three complimentary experiments in non-human
      primates, indicating task-specific changes in tonic BG pathway weightings during
      saccade behavior with different cognitive demands. First, simultaneous local
      field potential recording in the subthalamic nucleus (STN; BG input) and
      substantia nigra pars reticulata (SNr; BG output) reveals task-dependent shifts
      in subthalamo-nigral signals. Second, unilateral electrical stimulation of the
      STN, SNr, and caudate nucleus results in strikingly different saccade
      directionality and latency biases across the BG. Third, a simple artificial
      neural network representing canonical BG signaling pathways suggests that pathway
      weightings can be altered by cortico-BG input activation. Overall, inhibitory
      pathways (striato-pallidal-subthalamo-nigral) dominate during goal-driven
      behavior with instructed rewards, while facilitatory pathways (striato-nigral and
      subthalamo-pallidal-nigral) dominate during unconstrained (free reward)
      conditions.

PMID- 29051498
TI  - Normal and inverted regimes of charge transfer controlled by density of states at
      polymer electrodes.
AB  - Conductive polymer electrodes have exceptional promise for next-generation
      bioelectronics and energy conversion devices due to inherent mechanical
      flexibility, printability, biocompatibility, and low cost. Conductive polymers
      uniquely exhibit hybrid electronic-ionic transport properties that enable novel
      electrochemical device architectures, an advantage over inorganic counterparts.
      Yet critical structure-property relationships to control the potential-dependent
      rates of charge transfer at polymer/electrolyte interfaces remain poorly
      understood. Herein, we evaluate the kinetics of charge transfer between
      electrodeposited poly-(3-hexylthiophene) films and a model redox-active molecule,
      ferrocenedimethanol. We show that the kinetics directly follow the potential
      dependent occupancy of electronic states in the polymer. The rate increases then
      decreases with potential (both normal and inverted kinetic regimes), a phenomenon
      distinct from inorganic semiconductors. This insight can be invoked to design
      polymer electrodes with kinetic selectivity toward redox active species and help
      guide synthetic approaches for the design of alternative device architectures and
      approaches.

PMID- 29051497
TI  - Achieving high-efficiency emission depletion nanoscopy by employing cross
      relaxation in upconversion nanoparticles.
AB  - Stimulated emission depletion microscopy provides a powerful sub-diffraction
      imaging modality for life science studies. Conventionally, stimulated emission
      depletion requires a relatively high light intensity to obtain an adequate
      depletion efficiency through only light-matter interaction. Here we show
      efficient emission depletion for a class of lanthanide-doped upconversion
      nanoparticles with the assistance of interionic cross relaxation, which
      significantly lowers the laser intensity requirements of optical depletion. We
      demonstrate two-color super-resolution imaging using upconversion nanoparticles
      (resolution ~ 66 nm) with a single pair of excitation/depletion beams. In
      addition, we show super-resolution imaging of immunostained cytoskeleton
      structures of fixed cells (resolution ~ 82 nm) using upconversion nanoparticles.
      These achievements provide a new perspective for the development of
      photoswitchable luminescent probes and will broaden the applications of
      lanthanide-doped nanoparticles for sub-diffraction microscopic imaging.

PMID- 29051500
TI  - Odour dialects among wild mammals.
AB  - Across multiple taxa, population structure and dynamics depend on effective
      signalling between individuals. Among mammals, chemical communication is arguably
      the most important sense, underpinning mate choice, parental care, territoriality
      and even disease transmission. There is a growing body of evidence that odours
      signal genetic information that may confer considerable benefits including
      inbreeding avoidance and nepotism. To date, however, there has been no clear
      evidence that odours encode population-level information in wild mammals. Here we
      demonstrate for the first time the existence of 'odour dialects' in genetically
      distinct mammalian subpopulations across a large geographical scale. We found
      that otters, Lutra lutra, from across the United Kingdom possess sex and
      biogeography-specific odours. Subpopulations with the most distinctive odour
      profiles are also the most genetically diverse but not the most genetically
      differentiated. Furthermore, geographic distance between individuals does not
      explain regional odour differences, refuting other potential explanations such as
      group odour sharing behaviour. Differences in the language of odours between
      subpopulations have the potential to affect individual interactions, which could
      impact reproduction and gene-flow.

PMID- 29051499
TI  - An integrative method to decode regulatory logics in gene transcription.
AB  - Modeling of transcriptional regulatory networks (TRNs) has been increasingly used
      to dissect the nature of gene regulation. Inference of regulatory relationships
      among transcription factors (TFs) and genes, especially among multiple TFs, is
      still challenging. In this study, we introduced an integrative method, LogicTRN,
      to decode TF-TF interactions that form TF logics in regulating target genes. By
      combining cis-regulatory logics and transcriptional kinetics into one single
      model framework, LogicTRN can naturally integrate dynamic gene expression data
      and TF-DNA-binding signals in order to identify the TF logics and to reconstruct
      the underlying TRNs. We evaluated the newly developed methodology using
      simulation, comparison and application studies, and the results not only show
      their consistence with existing knowledge, but also demonstrate its ability to
      accurately reconstruct TRNs in biological complex systems.

PMID- 29051501
TI  - Branched-chain amino acids and Alzheimer's disease: a Mendelian randomization
      analysis.
AB  - We conducted a two-sample Mendelian randomization study to test the hypothesis
      that raised plasma levels of the branched-chain amino acids isoleucine, leucine,
      and valine are associated with Alzheimer's disease (AD). From a genome-wide
      association study of 16,596 individuals of European ancestry, we obtained summary
      statistics for four independent single nucleotide polymorphisms (SNPs) associated
      with isoleucine levels and one SNP associated with both leucine and valine levels
      at genome-wide significance. Summary statistics of the associations of the five
      SNPs with AD were obtained from the International Genomics of Alzheimer's Project
      (17,008 AD cases and 37,154 controls). Based on four SNPs, the odds ratio of AD
      per genetically predicted one standard deviation higher isoleucine levels was
      1.35 (95% CI, 1.08-1.69; p = 0.007). The leucine- and valine-raising allele was
      not associated with AD (p = 0.46). These data suggest that a genetic
      predisposition to raised plasma isoleucine levels is positively associated with
      AD.

PMID- 29051503
TI  - A low lasing threshold and widely tunable spaser based on two dark surface
      plasmons.
AB  - We theoretically demonstrate a low threshold and widely tunable spaser based on a
      plasmonic nanostructure consisting of two sets of disk-rings (TSDR). The TSDR
      nanostructure supports two dark surface plasmons (SPs), which are excited
      simultaneously by two bright SPs at Fano dips. The two dark SPs support lower
      effective mode volume, higher quality factor and higher Purcell factors. When the
      dark SPs serve as the pumping and lasing mode of a spaser, the spaser has a lower
      lasing threshold, a higher pump absorption efficiency and a lower threshold
      absorbed pump power than the spaser based on a bright SP. In addition, the lasing
      and pumping wavelengths of the spaser proposed in this article can each be tuned
      over a very wide wavelength range. Our results should be significant for the
      development of spasers.

PMID- 29051502
TI  - Comparative transcriptomics reveal developmental turning points during
      embryogenesis of a hemimetabolous insect, the damselfly Ischnura elegans.
AB  - Identifying transcriptional changes during embryogenesis is of crucial importance
      for unravelling evolutionary, molecular and cellular mechanisms that underpin
      patterning and morphogenesis. However, comparative studies focusing on
      early/embryonic stages during insect development are limited to a few taxa.
      Drosophila melanogaster is the paradigm for insect development, whereas
      comparative transcriptomic studies of embryonic stages of hemimetabolous insects
      are completely lacking. We reconstructed the first comparative transcriptome
      covering the daily embryonic developmental progression of the blue-tailed
      damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative.
      We identified a "core" set of 6,794 transcripts - shared by all embryonic stages 
      which are mainly involved in anatomical structure development and cellular
      nitrogen compound metabolic processes. We further used weighted gene co
      expression network analysis to identify transcriptional changes during Odonata
      embryogenesis. Based on these analyses distinct clusters of transcriptional
      active sequences could be revealed, indicating that embryos at different
      development stages have their own transcriptomic profile according to the
      developmental events and leading to sequential reprogramming of metabolic and
      developmental genes. Interestingly, a major change in transcriptionally active
      sequences is correlated with katatrepsis (revolution) during mid-embryogenesis, a
      180 degrees  rotation of the embryo within the egg and specific to hemimetabolous
      insects.

PMID- 29051504
TI  - The exact phase diagram for a class of open multispecies asymmetric exclusion
      processes.
AB  - The asymmetric exclusion process is an idealised stochastic model of transport,
      whose exact solution has given important insight into a general theory of
      nonequilibrium statistical physics. In this work, we consider a totally
      asymmetric exclusion process with multiple species of particles on a one
      dimensional lattice in contact with reservoirs. We derive the exact
      nonequilibrium phase diagram for the system in the long time limit. We find two
      new phenomena in certain regions of the phase diagram: dynamical expulsion when
      the density of a species becomes zero throughout the system, and dynamical
      localisation when the density of a species is nonzero only within an interval far
      from the boundaries. We give a complete explanation of the macroscopic features
      of the phase diagram using what we call nested fat shocks.

PMID- 29051505
TI  - Large-scale genomic analyses reveal the population structure and evolutionary
      trends of Streptococcus agalactiae strains in Brazilian fish farms.
AB  - Streptococcus agalactiae is a major pathogen and a hindrance on tilapia farming
      worldwide. The aims of this work were to analyze the genomic evolution of
      Brazilian strains of S. agalactiae and to establish spatial and temporal
      relations between strains isolated from different outbreaks of streptococcosis. A
      total of 39 strains were obtained from outbreaks and their whole genomes were
      sequenced and annotated for comparative analysis of multilocus sequence typing,
      genomic similarity and whole genome multilocus sequence typing (wgMLST). The
      Brazilian strains presented two sequence types, including a newly described ST,
      and a non-typeable lineage. The use of wgMLST could differentiate each strain in
      a single clone and was used to establish temporal and geographical correlations
      among strains. Bayesian phylogenomic analysis suggests that the studied Brazilian
      population was co-introduced in the country with their host, approximately 60
      years ago. Brazilian strains of S. agalactiae were shown to be heterogeneous in
      their genome sequences and were distributed in different regions of the country
      according to their genotype, which allowed the use of wgMLST analysis to track
      each outbreak event individually.

PMID- 29051506
TI  - An integrated EEG and eye-tracking approach for the study of responding and
      initiating joint attention in Autism Spectrum Disorders.
AB  - Autism Spectrum Disorders (ASD) are characterised by impairment in joint
      attention (JA), which has two components: the response to JA and the initiation
      of JA. Literature suggests a correlation between JA and neural circuitries,
      although this link is still largely unexplored in ASD. In this pilot study, we
      aimed at investigating the neural correlates of responding and initiating JA in
      high-functioning children with ASD and evaluating the changes in brain function
      and visual pattern after six months of rehabilitative treatment using an
      integrated EEG/eye-tracking system. Our results showed that initiating and
      responding JA subtend both overlapping (i.e. frontal and temporal) and
      specialized (i.e. parietal for responding JA and occipital for initiating JA)
      neural circuitries. In addition, in a subgroup of subjects, we observed trends of
      changes in both brain activity and connectivity after rehabilitative treatment in
      both the two tasks, which were correlated with modifications in gaze measures.
      These preliminary results, if confirmed in a larger sample, suggest the
      feasibility of using the proposed multimodal approach to characterise JA-related
      brain circuitries and visual pattern in ASD individuals and to monitor
      longitudinal changes in response to rehabilitative intervention.

PMID- 29051507
TI  - A new description of epileptic seizures based on dynamic analysis of a
      thalamocortical model.
AB  - Increasing evidence suggests that the brain dynamics can be interpreted from the
      viewpoint of nonlinear dynamical systems. The aim of this paper is to investigate
      the behavior of a thalamocortical model from this perspective. The model includes
      both cortical and sensory inputs that can affect the dynamic nature of the model.
      Driving response of the model subjected to various harmonic stimulations is
      considered to identify the effects of stimulus parameters on the cortical output.
      Detailed numerical studies including phase portraits, Poincare maps and
      bifurcation diagrams reveal a wide range of complex dynamics including period
      doubling and chaos in the output. Transition between different states can occur
      as the stimulation parameters are changed. In addition, the amplitude jump
      phenomena and hysteresis are shown to be possible as a result of the bending in
      the frequency response curve. These results suggest that the jump phenomenon due
      to the brain nonlinear resonance can be responsible for the transitions between
      ictal and interictal states.

PMID- 29051508
TI  - Lasing with cell-endogenous fluorophores: parameters and conditions.
AB  - The notion of lasing with biologics has recently been realized and has rapidly
      developed with the collective objective of creating lasers in vivo. One major
      limitation of achieving this is the requirement of exogenous dyes and fluorescent
      materials. We thus investigate for the first time the possibility of lasing
      unlabelled cells, using just cell-endogenous fluorophores - the source of cell
      autofluorescence. In this work, we theoretically studied the lasing potential and
      efficiency of flavins and reduced nicotinamide adenine dinucleotide (phosphate)
      (NAD(P)H) using a dye lasing model based on coupled rate equations. Analytical
      solutions for one- and two-photon pumped system were used in multi-parameter
      studies. We found that at physiological conditions, the more abundant NAD(P)H can
      be lased with a cavity quality factor of 105. We then recommended the tuning of
      intersystem crossing to make the lasing of flavins feasible even at their low
      physiological concentrations. Under conditions of reduced intersystem crossing,
      we concluded that it is more practical to lase unlabelled cells using flavins,
      because lasing thresholds and cavity quality factors were both at least an order
      lower. We also note the higher threshold requirements and lower efficiencies of
      two-photon pumping, but recognize its potential for realizing lasing in vivo.

PMID- 29051509
TI  - The transcriptional regulator NtrC controls glucose-6-phosphate dehydrogenase
      expression and polyhydroxybutyrate synthesis through NADPH availability in
      Herbaspirillum seropedicae.
AB  - The NTR system is the major regulator of nitrogen metabolism in Bacteria. Despite
      its broad and well-known role in the assimilation, biosynthesis and recycling of
      nitrogenous molecules, little is known about its role in carbon metabolism. In
      this work, we present a new facet of the NTR system in the control of NADPH
      concentration and the biosynthesis of molecules dependent on reduced coenzyme in
      Herbaspirillum seropedicae SmR1. We demonstrated that a ntrC mutant strain
      accumulated high levels of polyhydroxybutyrate (PHB), reaching levels up to 2
      fold higher than the parental strain. In the absence of NtrC, the activity of
      glucose-6-phosphate dehydrogenase (encoded by zwf) increased by 2.8-fold,
      consequently leading to a 2.1-fold increase in the NADPH/NADP+ ratio. A GFP
      fusion showed that expression of zwf is likewise controlled by NtrC. The increase
      in NADPH availability stimulated the production of polyhydroxybutyrate regardless
      the C/N ratio in the medium. The mutant ntrC was more resistant to H2O2 exposure
      and controlled the propagation of ROS when facing the oxidative condition, a
      phenotype associated with the increase in PHB content.

PMID- 29051510
TI  - Origins and transformations of dissolved organic matter in large Arctic rivers.
AB  - Arctic river watersheds are important components of the global climate system and
      show an amplified response to climate change. Here, we characterize origins and
      transformations of dissolved organic matter (DOM) in five major Arctic rivers
      (Kolyma, Lena, Yenisei, Ob, Mackenzie) over 3 years with seasonal sampling
      periods using measurements of carbohydrates, amino acids, bacterial biomarkers (D
      amino acids), and plant protein biomarkers (hydroxyproline). A strong seasonal
      cycle of bioavailable DOM export was observed that correlated with discharge,
      vegetation, river morphology and water residence time. The chemical composition
      of bioavailable DOM was different among rivers reflecting unique characteristics
      of Arctic river watersheds. Trends in specific bacterial biomarkers were
      synchronous to changes in bacterial community compositions demonstrating that
      bacterial communities responded to the seasonal shifts in organic matter quality
      and chemical composition. Extensive heterotrophic processing of plant and soil
      derived DOM resulted in major inputs of bacterial detritus, and bacterial organic
      matter accounted for 21-42% of DOC in all watersheds. Dissolved organic nitrogen
      sources were dominated by bacterially-derived nitrogen and important
      contributions of soluble plant protein during the Spring freshet. Overall, our
      results demonstrated the importance of watershed characteristics and bacterial
      metabolism in regulating DOM composition, reactivity and carbon fluxes in Arctic
      river watersheds.

PMID- 29051511
TI  - Prospective Study of Stereotactic Body Radiation Therapy for Thymoma and Thymic
      Carcinoma: Therapeutic Effect and Toxicity Assessment.
AB  - Stereotactic body radiation therapy (SBRT) is an important modality in treatment
      of tumors. We hypothesized that SBRT can achieve excellent local control with
      limited toxicity in patients with thymic tumors. A single-institution prospective
      study was performed with 32 patients who underwent SBRT of thymoma and thymic
      carcinoma between 2005 and 2014. Thirty-two patients including 39 target lesions
      were analyses in this study. Almost half of the patients (46.9%) were type C by
      histopathology and more than half (56.3%) were classified into stage IVA or IVB.
      The median dose of SBRT for gross tumor volume (GTV) was 56 Gy (range 49-70 Gy).
      Results showed that the response rate was 96.9% after SBRT and the median tumor
      shrinkage rate was 62.2% (range 3.8-100%). For the patients with both stage II
      III and type A-B (n = 6), the median PFS was 28 months. In-field failure was only
      observed in 4 patients, and outside-field failure was seen in 2 patients. The
      local control rate was 81.25%. Patients treated with SBRT had an excellent local
      control with mild toxicities, which suggests that SBRT is feasible for the
      patients with thymic tumors who are unable to undergo either surgery or
      conventionally fractionated radiation therapy.

PMID- 29051512
TI  - Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication
      of Cd300f in Multiple Sclerosis.
AB  - Herein, we have used bioinformatics tools to predict five clusters defining
      ligand-binding sites on the extracellular domain of human CD300b receptor,
      presumably involved in the formation of both homodimers and heterodimers with
      other CD300 family members. Site-directed mutagenesis revealed residues glutamic
      acid 28 and glutamine 29 in cluster 5 to be necessary for the formation of CD300b
      complexes. Surprisingly, the disruption of cluster 2 and 4 reconstituted the
      binding capability lost by the mutation of residues glutamic acid 28 to alanine,
      glutamine 29 to alanine (E28A-Q29G). We identified a missense mutation arginine
      33 to glutamine (R33Q) in CD300f by direct sequencing of exon 2 in peripheral
      blood samples from 50 patients with multiple sclerosis (MS). Levels of expression
      of CD300f were almost undetectable on monocytes from the patient bearing the R33Q
      mutation compared with healthy individuals. Whereas R33Q mutation had no effect
      in the formation of CD300f complexes, the inhibition of protein synthesis with
      cycloheximide indicated that CD300f R33Q is less stable than native CD300f.
      Finally, we report that the levels of expression of CD300f on the surface of
      classical and intermediate monocytes from MS patients are significantly lower
      when compared to the same cell populations in healthy individuals.

PMID- 29051513
TI  - Correlation between crystallographic anisotropy and dendritic orientation
      selection of binary magnesium alloys.
AB  - Both synchrotron X-ray tomography and EBSD characterization revealed that the
      preferred growth directions of magnesium alloy dendrite change as the type and
      amount of solute elements. Such growth behavior was further investigated by
      evaluating the orientation-dependent surface energy and the subsequent
      crystallographic anisotropy via ab-initio calculations based on density
      functional theory and hcp lattice structure. It was found that for most binary
      magnesium alloys, the preferred growth direction of the alpha-Mg dendrite in the
      basal plane is always [Formula: see text], and independent on either the type or
      concentration of the additional elements. In non-basal planes, however, the
      preferred growth direction is highly dependent on the solute concentration. In
      particular, for Mg-Al alloys, this direction changes from [Formula: see text] to
      [Formula: see text] as the Al-concentration increased, and for Mg-Zn alloys, this
      direction changes from [Formula: see text] to [Formula: see text] or [Formula:
      see text] as the Zn-content varied. Our results provide a better understanding on
      the dendritic orientation selection and morphology transition of magnesium alloys
      at the atomic level.

PMID- 29051514
TI  - Evidence for long-term sensitization of the bowel in patients with post
      infectious-IBS.
AB  - Post-infectious irritable bowel syndrome (PI-IBS) is a common gastrointestinal
      disorder characterized by persistent abdominal pain despite recovery from acute
      gastroenteritis. The underlying mechanisms are unclear, although long-term
      changes in neuronal function, and low grade inflammation of the bowel have been
      hypothesized. We investigated the presence and mechanism of neuronal
      sensitization in a unique cohort of individuals who developed PI-IBS following
      exposure to contaminated drinking water 7 years ago. We provide direct evidence
      of ongoing sensitization of neuronal signaling in the bowel of patients with PI
      IBS. These changes occur in the absence of any detectable tissue inflammation,
      and instead appear to be driven by pro-nociceptive changes in the gut micro
      environment. This is evidenced by the activation of murine colonic afferents, and
      sensitization responses to capsaicin in dorsal root ganglia (DRGs) following
      application of supernatants generated from tissue biopsy of patients with PI-IBS.
      We demonstrate that neuronal signaling within the bowel of PI-IBS patients is
      sensitized 2 years after the initial infection has resolved. This sensitization
      appears to be mediated by a persistent pro-nociceptive change in the gut micro
      environment, that has the capacity to stimulate visceral afferents and facilitate
      neuronal TRPV1 signaling.

PMID- 29051515
TI  - Antioxidant enzymes in chickpea colonized by Piriformospora indica participate in
      defense against the pathogen Botrytis cinerea.
AB  - Piriformospora indica, a root endophytic fungus, promotes growth of the
      economically important chickpea plant (Cicer arietinum Linn.) and protects it
      against the pathogenic fungus Botrytis cinerea. Biomass and root development were
      found to be significantly improved in chickpea plants colonized with P. indica as
      compared to the plants grown without P. indica as well as from the plants
      infected with the B. cinerea. Our PCR analyses showed that gradual increase in
      the colonization of P. indica in the plants result in the inhibition of the
      colonization of B. cinerea. P. indica colonized plants showed increased
      antioxidant enzyme activities. Interestingly, there were pronounced decrease in
      the antioxidant enzyme activities in shoots infected with B. cinerea and
      colonized with P. indica in alternate and simultaneous mode as compared to plants
      infected with B. cinerea alone. We conclude that P. indica helps plants to
      overcome the disease load by enhancing antioxidant enzyme defense system. Our
      data suggest that, bio-protective action of P. indica might be mediated via
      systemic induction of antioxidant defense in the host plants.

PMID- 29051517
TI  - Human attention affects facial expressions in domestic dogs.
AB  - Most mammalian species produce facial expressions. Historically, animal facial
      expressions have been considered inflexible and involuntary displays of emotional
      states rather than active attempts to communicate with others. In the current
      study, we aimed to test whether domestic dog facial expressions are subject to
      audience effects and/ or changes in response to an arousing stimulus (e.g. food)
      alone. We presented dogs with an experimental situation in which a human
      demonstrator was either attending to them or turned away, and varied whether she
      presented food or not. Dogs produced significantly more facial movements when the
      human was attentive than when she was not. The food, however, as a non-social but
      arousing stimulus, did not affect the dogs' behaviour. The current study is
      therefore evidence that dogs are sensitive to the human's attentional state when
      producing facial expressions, suggesting that facial expressions are not just
      inflexible and involuntary displays of emotional states, but rather potentially
      active attempts to communicate with others.

PMID- 29051516
TI  - Stromal striae: a new insight into corneal physiology and mechanics.
AB  - We uncover the significance of a previously unappreciated structural feature in
      corneal stroma, important to its biomechanics. Vogt striae are a known clinical
      indicator of keratoconus, and consist of dark, vertical lines crossing the
      corneal depth. However we detected stromal striae in most corneas, not only
      keratoconus. We observed striae with multiple imaging modalities in 82% of 118
      human corneas, with pathology-specific differences. Striae generally depart from
      anchor points at Descemet's membrane in the posterior stroma obliquely in a V
      shape, whereas in keratoconus, striae depart vertically from posterior toward
      anterior stroma. Optical coherence tomography shear wave elastography showed
      discontinuity of rigidity, and second harmonic generation and scanning electron
      microscopies showed undulation of lamellae at striae locations. Striae visibility
      decreased beyond physiological pressure and increased beyond physiological
      hydration. Immunohistology revealed striae to predominantly contain collagen VI,
      lumican and keratocan. The role of these regions of collagen VI linking sets of
      lamellae may be to absorb increases in intraocular pressure and external shocks.

PMID- 29051518
TI  - The years of life lost on cardiovascular disease attributable to ambient
      temperature in China.
AB  - Few studies have examined the association between ambient temperature and years
      of life lost (YLL). We aim to explore the burden of cardiovascular disease
      attributed to non-optimum temperature in China. YLL provides a complementary
      measure for examining the burden of disease due to ambient temperature. Non
      optimal temperature leads to the increase of YLL. The mortality of fourteen
      cities in China during 2008-2013 was included in this study. We used the
      Distributed Lag Non-linear Model (DLNM) to estimate the association between daily
      mean temperature and YLL, controlling for long term trends, day of the week,
      seasonality and relative humidity. The daily YLL varied from 807 in Changchun to
      2751 in Chengdu, with males higher than females. Extreme high and low
      temperatures were associated with higher YLL. The attributable fraction (AF) to
      cold effect is from 2.67 (95%CI: -1.63, 6.70) to 8.55 (95%CI: 5.05, 11.90), while
      the AF to heat effect is from 0.16 (95%CI: 0.06, 0.26) to 2.29 (95%CI: 1.29,
      3.19). Cold effect was significantly higher than heat effect on cardiovascular
      disease in both men and women and for different age groups.

PMID- 29051519
TI  - From Porous to Dense Nanostructured beta-Ti alloys through High-Pressure Torsion.
AB  - beta-Ti alloys have low elastic modulus, good specific strength and high
      corrosion resistance for biomaterial applications. Noble elements, such as Nb, Ta
      and Mo, are used to obtain beta-Ti due to their chemical biocompatibility.
      However, due to their refractory nature, beta-Ti requires specific processing
      routes. Powder metallurgy (P/M) allows for the development of new beta-Ti alloys
      with decreasing costs, but dealing with high-elemental-content alloys can lead to
      a lack of diffusion and grain growth. One method to refine the structure and
      improve mechanical properties is a severe plastic deformation technique through
      high-pressure torsion (HPT). The aim of this work was to evaluate the conversion
      of P/M porous beta-Ti-35Nb-10Ta-xFe alloys to dense nanostructures through high
      pressure torsion in one deformation step and the influence of the structure
      variation on the properties and microstructure. TEM analysis and ASTAR
      crystallographic mapping was utilized to characterize the nanostructures, and the
      properties of P/M beta Ti-35Nb-10Ta-xFe alloys processed by HPT were compared.
      The initial microstructure consisted mainly by the beta-Ti phase with some alpha
      Ti phase at the grain boundaries. The HPT process refined the microstructure from
      50 um (P/M) down to nanostructured grains of approximately 50 nm.

PMID- 29051520
TI  - Longitudinal assessment of HLA and MIC-A antibodies in uneventful pregnancies and
      pregnancies complicated by preeclampsia or gestational diabetes.
AB  - The significance of antibodies directed against paternal epitopes in the context
      of obstetric disorders is discussed controversially. In this study anti-HLA and
      anti-MIC-A antibodies were analysed in sera of women with uneventful pregnancy (n
      = 101), preeclampsia (PE, n = 55) and gestational diabetes (GDM, n = 36) using
      antigen specific microbeads. While two thirds of the women with uneventful
      pregnancy or GDM were HLA and MIC-A antibody positive in gestational week 11 to
      13 with a modest increase towards the end of pregnancy, women with PE showed an
      inverse kinetic: 90% were HLA antibody positive in gestational week 11 to 13 and
      only 10% showed HLA reactivities at the end of the pregnancy. HLA antibody
      binding strength was more pronounced in gestational week 14 to 17 in patients
      with PE compared to women with uneventful pregnancy (maximum median fluorescence
      intensity of the highest ranked positive bead 7403, IQR 2193-7938 vs. 1093, IQR
      395-5689; p = 0.04) and was able to predict PE with an AUC of 0.80 (95% CI 0.67
      0.93; p = 0.002). Our data suggest a pathophysiological involvement of HLA
      antibodies in PE. HLA antibody quantification in early pregnancy may provide a
      useful tool to increase diagnostic awareness in women prone to develop PE.

PMID- 29051521
TI  - Evaluating feasibility of an automated 3-dimensional scanner using Raman
      spectroscopy for intraoperative breast margin assessment.
AB  - Breast conserving surgery is the preferred treatment for women diagnosed with
      early stage invasive breast cancer. To ensure successful breast conserving
      surgeries, efficient tumour margin resection is required for minimizing tumour
      recurrence. Currently surgeons rely on touch preparation cytology or frozen
      section analysis to assess tumour margin status intraoperatively. These
      techniques have suboptimal accuracy and are time-consuming. Tumour margin status
      is eventually confirmed using postoperative histopathology that takes several
      days. Thus, there is a need for a real-time, accurate, automated guidance tool
      that can be used during tumour resection intraoperatively to assure complete
      tumour removal in a single procedure. In this paper, we evaluate feasibility of a
      3-dimensional scanner that relies on Raman Spectroscopy to assess the entire
      margins of a resected specimen within clinically feasible time. We initially
      tested this device on a phantom sample that simulated positive tumour margins.
      This device first scans the margins of the sample and then depicts the margin
      status in relation to an automatically reconstructed image of the phantom sample.
      The device was further investigated on breast tissues excised from prophylactic
      mastectomy specimens. Our findings demonstrate immense potential of this device
      for automated breast tumour margin assessment to minimise repeat invasive
      surgeries.

PMID- 29051522
TI  - Marine biogeographic realms and species endemicity.
AB  - Marine biogeographic realms have been inferred from small groups of species in
      particular environments (e.g., coastal, pelagic), without a global map of realms
      based on statistical analysis of species across all higher taxa. Here we analyze
      the distribution of 65,000 species of marine animals and plants, and distinguish
      30 distinct marine realms, a similar proportion per area as found for land. On
      average, 42% of species are unique to the realms. We reveal 18 continental-shelf
      and 12 offshore deep-sea realms, reflecting the wider ranges of species in the
      pelagic and deep-sea compared to coastal areas. The most widespread species are
      pelagic microscopic plankton and megafauna. Analysis of pelagic species
      recognizes five realms within which other realms are nested. These maps integrate
      the biogeography of coastal and deep-sea, pelagic and benthic environments, and
      show how land-barriers, salinity, depth, and environmental heterogeneity relate
      to the evolution of biota. The realms have applications for marine reserves,
      biodiversity assessments, and as an evolution relevant context for climate change
      studies.

PMID- 29051523
TI  - Emotion Regulating Attentional Control Abnormalities In Major Depressive
      Disorder: An Event-Related Potential Study.
AB  - Major depressive disorders (MDD) exhibit cognitive dysfunction with respect to
      attention. The deficiencies in cognitive control of emotional information are
      associated with MDD as compared to healthy controls (HC). However, the brain
      mechanism underlying emotion that influences the attentional control in MDD
      necessitates further research. The present study explores the emotion-regulated
      cognitive competence in MDD at a dynamic attentional stage. Event-Related
      Potentials (ERPs) were recorded from 35 clinical MDD outpatients and matched HCs
      by applying a modified affective priming dot-probe paradigm, which consisted of
      various emotional facial expression pairs. From a dynamic perspective, ERPs
      combined with sLORETA results showed significant differences among the groups. In
      compared to HC, 100 ms MDD group exhibited a greater interior-prefrontal N100,
      sensitive to negative-neutral faces. 200 ms MDD showed an activated parietal
      occipital P200 linked to sad face, suggesting that the attentional control
      ability concentrated on sad mood-congruent cognition. 300 ms, a distinct P300 was
      observed at dorsolateral parietal cortex, representing a sustained attentional
      control. Our findings suggested that a negatively sad emotion influenced
      cognitive attentional control in MDD in the early and late attentional stages of
      cognition. P200 and P300 might be predictors of potential neurocognitive
      mechanism underlying the dysregulated attentional control of MDD.

PMID- 29051524
TI  - The international staging system improves the IPI risk stratification in patients
      with diffuse large B-cell lymphoma treated with R-CHOP.
AB  - The international staging system (ISS), based on serum beta-2 microglobulin and
      albumin, is used to predict survival in multiple myeloma, but its prognostic
      significance in diffuse large B-cell lymphoma (DLBCL) remains unknown. Herein, we
      retrospectively analyzed 215 de novo DLBCL patients. According to ISS, there were
      90 of 215 (41.9%) patients in stage I, 98 of 215 (45.6%) in stage II and 27 of
      215 (12.6%) in stage III group. Patients with ISS stage II/III showed shorter
      overall survival (OS) and event free survival (EFS) than those with stage I
      treated with R-CHOP (p = 0.012 and p = 0.043, respectively), but not those
      treated with CHOP regimen (p > 0.05). Multivariable analysis revealed that ISS,
      independent of IPI, indicated different survival in both OS (HR, 5.690; 95% CI,
      1.270-25.495, p = 0.023) and EFS (HR, 2.116; 95% CI, 1.005-4.455, p = 0.049) in
      DLBCL patients treated with R-CHOP. ISS could identify patients with better
      outcome in intermediate-high/high IPI risk patients (p < 0.05). Our data suggests
      that advanced ISS stage is associated with inferior outcome in DLBCL patients
      treated with R-CHOP. ISS could identify a subgroup of DLBCL patients with
      superior outcome from high IPI risk patients, which may help to avoid intensive
      therapy.

PMID- 29051525
TI  - Virulence Characteristics of Carbapenem-Resistant Klebsiella pneumoniae Strains
      from Patients with Necrotizing Skin and Soft Tissue Infections.
AB  - Two types of Klebsiella pneumoniae (KP) strains are currently emerging:
      hypervirulent (hvKP) strains and carbapenem-resistant (CR-KP) strains. To date,
      these two strain types rarely overlap. Recent reports, however, suggest that CR
      KP strains are increasing in virulence. hvKP strains frequently present as highly
      invasive infections, such as necrotizing skin and soft tissue infections (NSSTI).
      To examine whether CR-KP strains with features of hvKP were present in our U.S.
      hospital, we retrospectively identified four cases of CR-KP NSSTI diagnosed
      between January 2012 and January 2016. Whole-genome sequencing was used to
      perform multilocus sequence typing, capsular typing, and identification of
      virulence and antimicrobial resistance genes. Additionally, the virulence of each
      isolate was determined in vitro and using murine pneumonia and subcutaneous
      infection models. We identified one CR-KP isolate that possessed features of
      hypervirulent KP, including a hypermucoviscous phenotype, K2 capsule, and
      resistance to phagocytosis. Of the four CR-KP isolates, two had no evidence of
      enhanced pathogenicity in either mouse model, demonstrating that low-virulence
      strains can cause NSSTI in immunosuppressed patients. The remaining two isolates
      exhibited low virulence in the pneumonia model but high virulence in the
      subcutaneous infection model, suggesting that the virulence attributes of these
      isolates are adapted to causing NSSTI.

PMID- 29051526
TI  - Arginase Structure and Inhibition: Catalytic Site Plasticity Reveals New
      Modulation Possibilities.
AB  - Metalloenzyme arginase is a therapeutically relevant target associated with tumor
      growth. To fight cancer immunosuppression, arginase activity can be modulated by
      small chemical inhibitors binding to its catalytic center. To better understand
      molecular mechanisms of arginase inhibition, a careful computer-aided mechanistic
      structural investigation of this enzyme was conducted. Using molecular dynamics
      (MD) simulations in the microsecond range, key regions of the protein active site
      were identified and their flexibility was evaluated and compared. A cavity
      opening phenomenon was observed, involving three loops directly interacting with
      all known ligands, while metal coordinating regions remained motionless. A novel
      dynamic 3D pharmacophore analysis method termed dynophores has been developed
      that allows for the construction of a single 3D-model comprising all ligand
      enzyme interactions occurring throughout a complete MD trajectory. This new
      technique for the in silico study of intermolecular interactions allows for loop
      flexibility analysis coupled with movements and conformational changes of bound
      ligands. Presented MD studies highlight the plasticity of the size of the
      arginase active site, leading to the hypothesis that larger ligands can enter the
      cavity of arginase. Experimental testing of a targeted fragment library
      substituted by different aliphatic groups validates this hypothesis, paving the
      way for the design of arginase inhibitors with novel binding patterns.

PMID- 29051528
TI  - Induced seismicity closed-form traffic light system for actuarial decision-making
      during deep fluid injections.
AB  - The rise in the frequency of anthropogenic earthquakes due to deep fluid
      injections is posing serious economic, societal, and legal challenges to many geo
      energy and waste-disposal projects. Existing tools to assess such problems are
      still inherently heuristic and mostly based on expert elicitation (so-called
      clinical judgment). We propose, as a complementary approach, an adaptive traffic
      light system (ATLS) that is function of a statistical model of induced
      seismicity. It offers an actuarial judgement of the risk, which is based on a
      mapping between earthquake magnitude and risk. Using data from six underground
      reservoir stimulation experiments, mostly from Enhanced Geothermal Systems, we
      illustrate how such a data-driven adaptive forecasting system could guarantee a
      risk-based safety target. The proposed model, which includes a linear
      relationship between seismicity rate and flow rate, as well as a normal diffusion
      process for post-injection, is first confirmed to be representative of the data.
      Being integrable, the model yields a closed-form ATLS solution that is both
      transparent and robust. Although simulations verify that the safety target is
      consistently ensured when the ATLS is applied, the model from which simulations
      are generated is validated on a limited dataset, hence still requiring further
      tests in additional fluid injection environments.

PMID- 29051527
TI  - Micro-ribonucleic acids and extracellular vesicles repertoire in the spent
      culture media is altered in women undergoing In Vitro Fertilization.
AB  - MicroRNAs (miRNAs) are class of small RNA molecules with major impact on gene
      regulation. We analyzed the potential of miRNAs secreted from pre-implantation
      embryos into the embryonic culture media as biomarkers to predict successful
      pregnancy. Using microarray analysis, we profiled the miRNome of the 56 spent
      culture media (SCM) after embryos transfer and found a total of 621 miRNAs in the
      SCM. On average, we detected 163 miRNAs in SCM of samples with failed
      pregnancies, but only 149 SCM miRNAs of embryos leading to pregnancies. MiR-634
      predicted an embryo transfer leading to a positive pregnancy with an accuracy of
      71% and a sensitivity of 85%. Among the 621 miRNAs, 102 (16.4%) showed a
      differential expression between positive and negative outcome of pregnancy with
      miR-29c-3p as the most significantly differentially expressed miRNA. The number
      of extracellular vehicles was lower in SCM with positive outcomes (3.8 * 109/mL
      EVs), as compared to a negative outcome (7.35 * 109/mL EVs) possibly explaining
      the reduced number of miRNAs in the SCM associated with failed pregnancies. The
      analysis of the miRNome in the SCM of couples undergoing fertility treatment lays
      the ground towards development of biomarkers to predict successful pregnancy and
      towards understanding the role of embryonic miRNAs found in the SCM.

PMID- 29051529
TI  - Dopamine-mediated photothermal theranostics combined with up-conversion platform
      under near infrared light.
AB  - An organic-inorganic hybrid core-shell nanostructure, based on mesoporous silica
      coated upconversion core-shell nanoparticles (NaGdF4:Yb,Er@NaGdF4:Yb@mSiO2-Dopa
      abbreviated here as UCNP@mSiO2-Dopa) that stably incorporates dopamine (Dopa) in
      the silica layer was introduced as a theranostic nanoplatform for optical imaging
      guided photothermal therapy (PTT) using NIR excitation. Silica-attaching
      polyethylenimine make the Dopa transforms into an active form (transferred Dopa)
      that strongly absorbs light under single 980 nm irradiation. We show that the
      activated UCNP@mSiO2-Dopa nanoplatform is able to produce a pronounced
      photothermal effect, that elevates water temperature from room temperature to
      41.8  degrees C within 2 minutes, while concurrently emitting strong upconverted
      luminescence (UCL) for visualized guidance under 980 nm laser. In addition, we
      demonstrate the application of the same UCNP@mSiO2-Dopa nanoplatform for magnetic
      resonance imaging (MRI) and x-ray computed tomography (CT) enabled by the
      gadolinium (Gd) element contained in the UCNP. Importantly, the in vitro and in
      vivo anti-cancer therapeutic effects have been shown efficacious, implying the
      use of the described nanoplatform as an effective multi-modal imaging enabled PTT
      agent. Results from the in vivo biodistribution of UCNPs@mSiO2, cellular
      live/dead assay, and histologic analysis of main organs of treated mice, reveal
      that the UCNP@mSiO2-Dopa agents are bio-compatible with low toxicity.

PMID- 29051530
TI  - Characterization of a dual function macrocyclase enables design and use of
      efficient macrocyclization substrates.
AB  - Peptide macrocycles are promising therapeutic molecules because they are protease
      resistant, structurally rigid, membrane permeable, and capable of modulating
      protein-protein interactions. Here, we report the characterization of the dual
      function macrocyclase-peptidase enzyme involved in the biosynthesis of the highly
      toxic amanitin toxin family of macrocycles. The enzyme first removes 10 residues
      from the N-terminus of a 35-residue substrate. Conformational trapping of the 25
      amino-acid peptide forces the enzyme to release this intermediate rather than
      proceed to macrocyclization. The enzyme rebinds the 25 amino-acid peptide in a
      different conformation and catalyzes macrocyclization of the N-terminal eight
      residues. Structures of the enzyme bound to both substrates and biophysical
      analysis characterize the different binding modes rationalizing the mechanism.
      Using these insights simpler substrates with only five C-terminal residues were
      designed, allowing the enzyme to be more effectively exploited in biotechnology.

PMID- 29051531
TI  - Gut microbiome alterations in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia. However, the
      etiopathogenesis of this devastating disease is not fully understood. Recent
      studies in rodents suggest that alterations in the gut microbiome may contribute
      to amyloid deposition, yet the microbial communities associated with AD have not
      been characterized in humans. Towards this end, we characterized the bacterial
      taxonomic composition of fecal samples from participants with and without a
      diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of
      AD participants has decreased microbial diversity and is compositionally distinct
      from control age- and sex-matched individuals. We identified phylum- through
      genus-wide differences in bacterial abundance including decreased Firmicutes,
      increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD
      participants. Furthermore, we observed correlations between levels of
      differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD.
      These findings add AD to the growing list of diseases associated with gut
      microbial alterations, as well as suggest that gut bacterial communities may be a
      target for therapeutic intervention.

PMID- 29051532
TI  - CCAAT/Enhancer binding protein beta silencing mitigates glial activation and
      neurodegeneration in a rat model of Parkinson's disease.
AB  - The CCAAT/Enhancer binding protein beta (C/EBPbeta) is a transcription factor
      involved in numerous physiological as well as pathological conditions in the
      brain. However, little is known regarding its possible role in neurodegenerative
      disorders. We have previously shown that C/EBPbeta regulates the expression of
      genes involved in inflammatory processes and brain injury. Here, we have analyzed
      the effects of C/EBPbeta interference in dopaminergic cell death and glial
      activation in the 6-hydroxydopamine model of Parkinson's disease. Our results
      showed that lentivirus-mediated C/EBPbeta deprivation conferred marked in vitro
      and in vivo neuroprotection of dopaminergic cells concomitant with a significant
      attenuation of the level of the inflammatory response and glial activation.
      Additionally, C/EBPbeta interference diminished the induction of alpha-synuclein
      in the substantia nigra pars compacta of animals injected with 6-hydroxydopamine.
      Taking together, these results reveal an essential function for C/EBPbeta in the
      pathways leading to inflammatory-mediated brain damage and suggest novel roles
      for C/EBPbeta in neurodegenerative diseases, specifically in Parkinson's disease,
      opening the door for new therapeutic interventions.

PMID- 29051533
TI  - Microtome-integrated microscope system for high sensitivity tracking of in-resin
      fluorescence in blocks and ultrathin sections for correlative microscopy.
AB  - Many areas of biological research demand the combined use of different imaging
      modalities to cover a wide range of magnifications and measurements or to place
      fluorescent patterns into an ultrastructural context. A technically difficult
      problem is the efficient specimen transfer between different imaging modalities
      without losing the coordinates of the regions-of-interest (ROI). Here, we report
      a new and highly sensitive integrated system that combines a custom designed
      microscope with an ultramicrotome for in-resin-fluorescence detection in blocks,
      ribbons and sections on EM-grids. Although operating with long-distance lenses,
      this system achieves a very high light sensitivity. Our instrumental set-up and
      operating workflow are designed to investigate rare events in large tissue
      volumes. Applications range from studies of individual immune, stem and cancer
      cells to the investigation of non-uniform subcellular processes. As a use case,
      we present the ultrastructure of a single membrane repair patch on a muscle fiber
      in intact muscle in a whole animal context.

PMID- 29051534
TI  - Surface marker profiling of SH-SY5Y cells enables small molecule screens
      identifying BMP4 as a modulator of neuroblastoma differentiation.
AB  - Neuroblastoma is the most common extra-cranial solid tumor in children. Its broad
      spectrum of clinical outcomes reflects the underlying inherent cellular
      heterogeneity. As current treatments often do not lead to tumor eradication,
      there is a need to better define therapy-resistant neuroblastoma and to identify
      new modulatory molecules. To this end, we performed the first comprehensive flow
      cytometric characterization of surface molecule expression in neuroblastoma cell
      lines. Exploiting an established clustering algorithm (SPADE) for unbiased
      visualization of cellular subsets, we conducted a multiwell screen for small
      molecule modulators of neuroblastoma phenotype. In addition to SH-SY5Y cells, the
      SH-EP, BE(2)-M17 and Kelly lines were included in follow-up analysis as in vitro
      models of neuroblastoma. A combinatorial detection of glycoprotein epitopes
      (CD15, CD24, CD44, CD57, TrkA) and the chemokine receptor CXCR4 (CD184) enabled
      the quantitative identification of SPADE-defined clusters differentially
      responding to small molecules. Exposure to bone morphogenetic protein (BMP)-4 was
      found to enhance a TrkAhigh/CD15-/CD184- neuroblastoma cellular subset,
      accompanied by a reduction in doublecortin-positive neuroblasts and of NMYC
      protein expression in SH-SY5Y cells. Beyond yielding novel marker candidates for
      studying neuroblastoma pathology, our approach may provide tools for improved
      pharmacological screens towards developing novel avenues of neuroblastoma
      diagnosis and treatment.

PMID- 29051535
TI  - The biomechanical origin of extreme wing allometry in hummingbirds.
AB  - Flying animals of different masses vary widely in body proportions, but the
      functional implications of this variation are often unclear. We address this
      ambiguity by developing an integrative allometric approach, which we apply here
      to hummingbirds to examine how the physical environment, wing morphology and
      stroke kinematics have contributed to the evolution of their highly specialised
      flight. Surprisingly, hummingbirds maintain constant wing velocity despite an
      order of magnitude variation in body weight; increased weight is supported solely
      through disproportionate increases in wing area. Conversely, wing velocity
      increases with body weight within species, compensating for lower relative wing
      area in larger individuals. By comparing inter- and intraspecific allometries, we
      find that the extreme wing area allometry of hummingbirds is likely an adaptation
      to maintain constant burst flight capacity and induced power requirements with
      increasing weight. Selection for relatively large wings simultaneously maximises
      aerial performance and minimises flight costs, which are essential elements of
      humming bird life history.

PMID- 29051536
TI  - Feasibility and physiological relevance of designing highly potent aminopeptidase
      sparing leukotriene A4 hydrolase inhibitors.
AB  - Leukotriene A4 Hydrolase (LTA4H) is a bifunctional zinc metalloenzyme that
      comprises both epoxide hydrolase and aminopeptidase activity, exerted by two
      overlapping catalytic sites. The epoxide hydrolase function of the enzyme
      catalyzes the biosynthesis of the pro-inflammatory lipid mediator leukotriene
      (LT) B4. Recent literature suggests that the aminopeptidase function of LTA4H is
      responsible for degradation of the tripeptide Pro-Gly-Pro (PGP) for which
      neutrophil chemotactic activity has been postulated. It has been speculated that
      the design of epoxide hydrolase selective LTA4H inhibitors that spare the
      aminopeptidase pocket may therefore lead to more efficacious anti-inflammatory
      drugs. In this study, we conducted a high throughput screen (HTS) for LTA4H
      inhibitors and attempted to rationally design compounds that would spare the PGP
      degrading function. While we were able to identify compounds with preference for
      the epoxide hydrolase function, absolute selectivity was not achievable for
      highly potent compounds. In order to assess the relevance of designing such
      aminopeptidase-sparing LTA4H inhibitors, we studied the role of PGP in inducing
      inflammation in different settings in wild type and LTA4H deficient (LTA4H KO)
      animals but could not confirm its chemotactic potential.  Attempting to design
      highly potent epoxide hydrolase selective LTA4H inhibitors, therefore seems to be
      neither feasible nor relevant.

PMID- 29051537
TI  - Microarray gene expression of periosteum in spontaneous bone regeneration of
      mandibular segmental defects.
AB  - Spontaneous bone regeneration could occur to reestablish mandibular bony
      continuity in patients who underwent partial or total mandibulectomy for tumors
      with periosteum-preserving. However, scarce data is available related to the
      precise role of periosteum in this bone regeneration. Therefore we aimed to
      investigate the gene expression of periosteum that were involved in the
      mandibular bone regeneration. Mandibular segmental defects were created in six
      mini-pigs with periosteum preserved. The periosteum of defects and control site
      were harvested at 1 and 2 weeks. Gene ontology (GO) analysis showed that the
      mechanisms concerning immature wound healing were clearly up-regulated at week 1.
      In contrast, by week-2, the GO categories of skeletal development, ossification
      and bone mineralization were significantly over-represented at week-2 with
      several genes encoding cell differentiation, extracellular matrix formation, and
      anatomical structure development. Furthermore, Tgfbeta/Bmp, Wnt and Notch
      signaling were all related to the osteogenic process in this study. Besides
      osteogenesis, genes related to angiogenesis and neurogenesis were also prominent
      at week-2. These findings revealed that the gene expression profile of the
      periosteum's cells participating in bone regeneration varied in different time
      points, and numbers of candidate genes that differentially expressed during early
      healing stages of intramembranous bone regeneration were suggested.

PMID- 29051538
TI  - Identification and characterization of a putative protein disulfide isomerase
      (HsPDI) as an alleged effector of Heterodera schachtii.
AB  - The plant-parasitic nematode Heterodera schachtii is an obligate biotroph that
      induces syncytial feeding sites in roots of its hosts. Nematodes produce
      effectors that are secreted into the host and facilitate infection process. Here
      we identified H. schachtii protein disulphide isomerase (HsPDI) as a putative
      effector that interferes with the host's redox status. In situ hybridization
      showed that HsPdi is specifically localized within esophageal glands of pre
      parasitic second stage juveniles (J2). HsPdi is up-regulated in the early
      parasitic J2s. Silencing of HsPdi by RNA interference in the J2s hampers their
      development and leads to structural malfunctions in associated feeding sites
      induced in Arabidopsis roots. Expression of HsPDI in Arabidopsis increases
      plant's susceptibility towards H. schachtii. HsPdi expression is up-regulated in
      the presence of exogenous H2O2, whereas HsPdi silencing results in increased
      mortality under H2O2 stress. Stable expression of HsPDI in Arabidopsis plants
      decreases ROS burst induced by flg22. Transiently expressed HsPDI in N.
      benthamiana leaves is localized in the apoplast. HsPDI plays an important role in
      the interaction between nematode and plant, probably through inducing local
      changes in the redox status of infected host tissue. It also contributes to
      protect the nematode from exogenous H2O2 stress.

PMID- 29051539
TI  - Ophthalmological symptoms in children with intracranial cysts.
AB  - The purpose of this study was to perform an ophthalmological assessment in
      children with intracranial cysts and to assess the correlation between the
      occurrence of cysts and visual disorders. The documentation of 46 children with
      intracranial cysts, monitored by the Children's Outpatient Ophthalmology Clinic,
      Poznan, Poland was analysed. The best corrected visual acuity (BCVA), the
      alignment of the eyes, visual evoked potentials (VEP), comprehensive eye
      examination were performed in all patients. Additional ophthalmological tests
      were conducted to eliminate other causes of decreased visual acuity.Included in
      the final analysis were 26 children (52 eyes). The average age at the last visit
      was 10.3 years. Sixteen children (61.5%) had arachnoid cysts located in the
      posterior cranial fossa, 3 children (11.5%) in the middle cranial fossa, while 7
      children (27%) had a pineal cyst. Decreased BCVA was found in 13 children,
      abnormal VEP in 13, strabismus in 14 patients (53.9%), nystagmus in 5 patients
      (19.2%), and double vision in 2 patients (7.7%). Numerous visual disorders in
      children with intracranial cysts suggest the necessity to carry out enhanced
      ophthalmological diagnostics in these patients. In the examined patient group,
      visual disorders occurred mostly in the case of arachnoid cysts of the posterior
      fossa.

PMID- 29051541
TI  - Helicity dependent photocurrent in electrically gated (Bi1-x Sb x )2Te3 thin
      films.
AB  - Circularly polarized photons are known to generate a directional helicity
      dependent photocurrent in three-dimensional topological insulators at room
      temperature. Surprisingly, the phenomenon is readily observed at photon energies
      that excite electrons to states far above the spin-momentum locked Dirac cone and
      the underlying mechanism for the helicity-dependent photocurrent is still not
      understood. Here we show a comprehensive study of the helicity-dependent
      photocurrent in (Bi1-x Sb x )2Te3 thin films as a function of the incidence angle
      of the optical excitation, its wavelength and the gate-tuned chemical potential.
      Our observations allow us to unambiguously identify the circular photo-galvanic
      effect as the dominant mechanism for the helicity-dependent photocurrent.
      Additionally, we use an analytical model to relate the directional nature of the
      photocurrent to asymmetric optical transitions between the topological surface
      states and bulk bands. The insights we obtain are important for engineering opto
      spintronic devices that rely on optical steering of spin and charge currents.

PMID- 29051540
TI  - Genome-wide association study identifies the SERPINB gene cluster as a
      susceptibility locus for food allergy.
AB  - Genetic factors and mechanisms underlying food allergy are largely unknown. Due
      to heterogeneity of symptoms a reliable diagnosis is often difficult to make.
      Here, we report a genome-wide association study on food allergy diagnosed by oral
      food challenge in 497 cases and 2387 controls. We identify five loci at genome
      wide significance, the clade B serpin (SERPINB) gene cluster at 18q21.3, the
      cytokine gene cluster at 5q31.1, the filaggrin gene, the C11orf30/LRRC32 locus,
      and the human leukocyte antigen (HLA) region. Stratifying the results for the
      causative food demonstrates that association of the HLA locus is peanut allergy
      specific whereas the other four loci increase the risk for any food allergy.
      Variants in the SERPINB gene cluster are associated with SERPINB10 expression in
      leukocytes. Moreover, SERPINB genes are highly expressed in the esophagus. All
      identified loci are involved in immunological regulation or epithelial barrier
      function, emphasizing the role of both mechanisms in food allergy.

PMID- 29051542
TI  - The efficacy and further functional advantages of random-base molecular barcodes
      for absolute and digital quantification of nucleic acid molecules.
AB  - Accurate quantification of biomolecules in system-wide measurements is in high
      demand, especially for systems with limited sample amounts such as single cells.
      Because of this, digital quantification of nucleic acid molecules using molecular
      barcodes has been developed, making, e.g., transcriptome analysis highly
      reproducible and quantitative. This counting scheme was shown to work using
      sequence-restricted barcodes, and non-sequence-restricted (random-base) barcodes
      that may provide a much higher dynamic range at significantly lower cost have
      been widely used. However, the efficacy of random-base barcodes is significantly
      affected by base changes due to amplification and/or sequencing errors and has
      not been investigated experimentally or quantitatively. Here, we show
      experimentally that random-base barcodes enable absolute and digital
      quantification of DNA molecules with high dynamic range (from one to more than
      104, potentially up to 1015 molecules) conditional on our barcode design and
      variety, a certain range of sequencing depths, and computational analyses.
      Moreover, we quantitatively show further functional advantages of the molecular
      barcodes: the molecular barcodes enable one to find contaminants and
      misidentifications of target sequences. Our scheme here may be generally used to
      confirm that the digital quantification works in each platform.

PMID- 29051544
TI  - Estimating prognosis in patients with acute myocardial infarction using
      personalized computational heart models.
AB  - Biomechanical computational models have potential prognostic utility in patients
      after an acute ST-segment-elevation myocardial infarction (STEMI). In a proof-of
      concept study, we defined two groups (1) an acute STEMI group (n = 6, 83% male,
      age 54 +/- 12 years) complicated by left ventricular (LV) systolic dysfunction;
      (2) an age- and sex- matched hyper-control group (n = 6, 83% male, age 46 +/- 14
      years), no prior history of cardiovascular disease and normal systolic blood
      pressure (SBP < 130 mmHg). Cardiac MRI was performed in the patients (2 days & 6
      months post-STEMI) and the volunteers, and biomechanical heart models were
      synthesized for each subject. The candidate parameters included normalized active
      tension (AT norm) and active tension at the resting sarcomere length (T req,
      reflecting required contractility). Myocardial contractility was inversely
      determined from personalized heart models by matching CMR-imaged LV dynamics.
      Compared with controls, patients with recent STEMI exhibited increased LV wall
      active tension when normalized by SBP. We observed a linear relationship between
      T req 2 days post-MI and global longitudinal strain 6 months later (r = 0.86; p =
      0.03). T req may be associated with changes in LV function in the longer term in
      STEMI patients complicated by LV dysfunction. Further studies seem warranted.

PMID- 29051545
TI  - One-dimensional Confinement Effect on the Self-assembly of Symmetric H-shaped
      Copolymers in a Thin Film.
AB  - The self-assembly of a reformed symmetric H-shaped copolymer with four
      hydrophilic branches and one hydrophobic stem was systematically investigated.
      The existence of vacancies is vital to regulate the sizes of self-assembled
      cylinders to be able to form a hexagonal arrangement. With the introduction of
      horizontal-orientated confinement, a micellar structure is formed through a
      coalescence mechanism. The short acting distance and large influencing area of
      the confinement produces numerous small-sized micelles. Additionally, the cycled
      "contraction-expansion" change helps achieve hexagonal arrangement. In contrast,
      the introduction of lateral-oriented confinement with long acting distance and
      small influencing area cannot change the cylindrical structure. Under the fission
      mechanism, in which the larger cylinder splits into smaller ones, it is quite
      efficient to generate hierarchical-sized cylinders from larger-sized cylinders in
      the middle region and smaller-sized cylinders near both walls. The results
      indicate the possibility of regulating the characteristics of a nanomaterial by
      tuning the molecular structure of the copolymer and the parameters of the
      introduced confinement, which are closely related to the self-assembly structure.

PMID- 29051543
TI  - CryoEM structure of Saccharomyces cerevisiae U1 snRNP offers insight into
      alternative splicing.
AB  - U1 snRNP plays a critical role in 5'-splice site recognition and is a frequent
      target of alternative splicing factors. These factors transiently associate with
      human U1 snRNP and are not amenable for structural studies, while their
      Saccharomyces cerevisiae (yeast) homologs are stable components of U1 snRNP.
      Here, we report the cryoEM structure of yeast U1 snRNP at 3.6 A resolution with
      atomic models for ten core proteins, nearly all essential domains of its RNA, and
      five stably associated auxiliary proteins. The foot-shaped yeast U1 snRNP
      contains a core in the "ball-and-toes" region architecturally similar to the
      human U1 snRNP. All auxiliary proteins are in the "arch-and-heel" region and
      connected to the core through the Prp42/Prp39 paralogs. Our demonstration that
      homodimeric human PrpF39 directly interacts with U1C-CTD, mirroring yeast
      Prp42/Prp39, supports yeast U1 snRNP as a model for understanding how transiently
      associated auxiliary proteins recruit human U1 snRNP in alternative splicing.

PMID- 29051546
TI  - Energy-efficient waveform for electrical stimulation of the cochlear nerve.
AB  - The cochlear implant (CI) is the most successful neural prosthesis, restoring the
      sensation of sound in people with severe-to-profound hearing loss by electrically
      stimulating the cochlear nerve. Existing CIs have an external, visible unit, and
      an internal, surgically-placed unit. There are significant challenges associated
      with the external unit, as it has limited utility and CI users often report a
      social stigma associated with prosthesis visibility. A fully-implantable CI
      (FICI) would address these issues. However, the volume constraint imposed on the
      FICI requires less power consumption compared to today's CI. Because neural
      stimulation by CI electrodes accounts for up to 90% of power consumption,
      reduction in stimulation power will result directly in CI power savings. To
      determine an energy-efficient waveform for cochlear nerve stimulation, we used a
      genetic algorithm approach, incorporating a computational model of a single
      mammalian myelinated cochlear nerve fiber coupled to a stimulator-electrode
      tissue interface. The algorithm's prediction was tested in vivo in human CI
      subjects. We find that implementation of a non-rectangular biphasic neural
      stimulation waveform may result in up to 25% charge savings and energy savings
      within the comfortable range of hearing for CI users. The alternative waveform
      may enable future development of a FICI.

PMID- 29051547
TI  - Narrow-bandwidth sensing of high-frequency fields with continuous dynamical
      decoupling.
AB  - State-of-the-art methods for sensing weak AC fields are only efficient in the low
      frequency domain (<10 MHz). The inefficiency of sensing high-frequency signals is
      due to the lack of ability to use dynamical decoupling. In this paper we show
      that dynamical decoupling can be incorporated into high-frequency sensing schemes
      and by this we demonstrate that the high sensitivity achieved for low frequency
      can be extended to the whole spectrum. While our scheme is general and suitable
      to a variety of atomic and solid-state systems, we experimentally demonstrate it
      with the nitrogen-vacancy center in diamond. For a diamond with natural abundance
      of 13C, we achieve coherence times up to 1.43 ms resulting in a smallest
      detectable magnetic field strength of 4 nT at 1.6 GHz. Attributed to the inherent
      nature of our scheme, we observe an additional increase in coherence time due to
      the signal itself.

PMID- 29051548
TI  - Gastrointestinal Hemorrhage after Spontaneous Subarachnoid Hemorrhage: A Single
      Center Cohort Study.
AB  - Spontaneous subarachnoid hemorrhage (SAH) is a devastating disease, and
      gastrointestinal hemorrhage is one of several potential complications of acute
      strokes. We aim to analyze its prevalence, risk factors, and association with in
      hospital prognosis following SAH. A total of 1047 adult patients with a primary
      diagnosis of spontaneous SAH were retrospectively enrolled. We retrieved medical
      information from the administrative database utilizing diagnostic and procedure
      codes of the International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM). Patients with SAH included 418 men and 629 women, and
      their mean age was 57.2 (standard deviation 14.6) years (range, 18-93 years).
      Gastrointestinal hemorrhage occurred in 30 of the 1047 patients, accounting for
      2.9%. In a multivariate logistic regression model, the independent risk factors
      for gastrointestinal hemorrhage were liver disease and hydrocephalus. The in
      hospital mortality rates were 43.3% and 29.3% in patients with and without
      gastrointestinal hemorrhage, respectively, but the difference was not
      statistically significant. In conclusion, the prevalence of gastrointestinal
      hemorrhage was 2.9% in patients hospitalized for spontaneous SAH. Underlying
      liver disease and the presence of hydrocephalus were both independent risk
      factors for this complication, which is a reminder to clinicians to pay increased
      attention in such cases.

PMID- 29051549
TI  - Chronic antidepressant potentiates spontaneous activity of dorsal raphe
      serotonergic neurons by decreasing GABAB receptor-mediated inhibition of L-type
      calcium channels.
AB  - Spontaneous activity of serotonergic neurons of the dorsal raphe nucleus (DRN)
      regulates mood and motivational state. Potentiation of serotonergic function is
      one of the therapeutic strategies for treatment of various psychiatric disorders,
      such as major depression, panic disorder and obsessive-compulsive disorder.
      However, the control mechanisms of the serotonergic firing activity are still
      unknown. In this study, we examined the control mechanisms for serotonergic
      spontaneous activity and effects of chronic antidepressant administration on
      these mechanisms by using modified ex vivo electrophysiological recording
      methods. Serotonergic neurons remained firing even in the absence of
      glutamatergic and GABAergic ionotropic inputs, while blockade of L-type voltage
      dependent Ca2+ channels (VDCCs) in serotonergic neurons decreased spontaneous
      firing activity. L-type VDCCs in serotonergic neurons received gamma-aminobutyric
      acid B (GABAB) receptor-mediated inhibition, which maintained serotonergic slow
      spontaneous firing activity. Chronic administration of an antidepressant,
      citalopram, disinhibited the serotonergic spontaneous firing activity by
      weakening the GABAB receptor-mediated inhibition of L-type VDCCs in serotonergic
      neurons. Our results provide a new mechanism underlying the spontaneous
      serotonergic activity and new insights into the mechanism of action of
      antidepressants.

PMID- 29051550
TI  - Studying the role of axon fasciculation during development in a computational
      model of the Xenopus tadpole spinal cord.
AB  - During nervous system development growing axons can interact with each other, for
      example by adhering together in order to produce bundles (fasciculation). How
      does such axon-axon interaction affect the resulting axonal trajectories, and
      what are the possible benefits of this process in terms of network function? In
      this paper we study these questions by adapting an existing computational model
      of the development of neurons in the Xenopus tadpole spinal cord to include
      interactions between axons. We demonstrate that even relatively weak attraction
      causes bundles to appear, while if axons weakly repulse each other their
      trajectories diverge such that they fill the available space. We show how
      fasciculation can help to ensure axons grow in the correct location for proper
      network formation when normal growth barriers contain gaps, and use a functional
      spiking model to show that fasciculation allows the network to generate reliable
      swimming behaviour even when overall synapse counts are artificially lowered.
      Although we study fasciculation in one particular organism, our approach to
      modelling axon growth is general and can be widely applied to study other nervous
      systems.

PMID- 29051552
TI  - Auditory evoked BOLD responses in awake compared to lightly anaesthetized zebra
      finches.
AB  - Functional magnetic resonance imaging (fMRI) is increasingly used in cognitive
      neuroscience and has become a valuable tool in the study of auditory processing
      in zebra finches, a well-established model of learned vocal communication. Due to
      its sensitivity to head motion, most fMRI studies in animals are performed in
      anaesthetized conditions, which might significantly impact neural activity evoked
      by stimuli and cognitive tasks. In this study, we (1) demonstrate the feasibility
      of fMRI in awake zebra finches and (2) explore how light anaesthesia regimes
      affect auditory-evoked BOLD responses to biologically relevant songs. After an
      acclimation procedure, we show that fMRI can be successfully performed during
      wakefulness, enabling the detection of reproducible BOLD responses to sound.
      Additionally, two light anaesthesia protocols were tested (isoflurane and a
      combination of medetomidine and isoflurane), of which isoflurane alone appeared
      to be the most promising given the high success rate, non-invasive induction, and
      quick recovery. By comparing auditory evoked BOLD responses in awake versus
      lightly anaesthetized conditions, we observed overall effects of anaesthetics on
      cerebrovascular reactivity as reflected in the extent of positive and negative
      BOLD responses. Further, our results indicate that light anaesthesia has limited
      effects on selective BOLD responses to natural versus synthetic sounds.

PMID- 29051551
TI  - Reducing sarcolipin expression mitigates Duchenne muscular dystrophy and
      associated cardiomyopathy in mice.
AB  - Sarcolipin (SLN) is an inhibitor of the sarco/endoplasmic reticulum (SR) Ca2+
      ATPase (SERCA) and is abnormally elevated in the muscle of Duchenne muscular
      dystrophy (DMD) patients and animal models. Here we show that reducing SLN levels
      ameliorates dystrophic pathology in the severe dystrophin/utrophin double mutant
      (mdx:utr -/-) mouse model of DMD. Germline inactivation of one allele of the SLN
      gene normalizes SLN expression, restores SERCA function, mitigates skeletal
      muscle and cardiac pathology, improves muscle regeneration, and extends the
      lifespan. To translate our findings into a therapeutic strategy, we knock down
      SLN expression in 1-month old mdx:utr -/- mice via adeno-associated virus (AAV) 9
      mediated RNA interference. The AAV treatment markedly reduces SLN expression,
      attenuates muscle pathology and improves diaphragm, skeletal muscle and cardiac
      function. Taken together, our findings suggest that SLN reduction is a promising
      therapeutic approach for DMD.

PMID- 29051553
TI  - 2D Raman band splitting in graphene: Charge screening and lifting of the K-point
      Kohn anomaly.
AB  - Pristine graphene encapsulated in hexagonal boron nitride has transport
      properties rivalling suspended graphene, while being protected from contamination
      and mechanical damage. For high quality devices, it is important to avoid and
      monitor accidental doping and charge fluctuations. The 2D Raman double peak in
      intrinsic graphene can be used to optically determine charge density, with
      decreasing peak split corresponding to increasing charge density. We find strong
      correlations between the 2D 1 and 2D 2 split vs 2D line widths, intensities, and
      peak positions. Charge density fluctuations can be measured with orders of
      magnitude higher precision than previously accomplished using the G-band shift
      with charge. The two 2D intrinsic peaks can be associated with the "inner" and
      "outer" Raman scattering processes, with the counterintuitive assignment of the
      phonon closer to the K point in the KM direction (outer process) as the higher
      energy peak. Even low charge screening lifts the phonon Kohn anomaly near the K
      point for graphene encapsulated in hBN, and shifts the dominant intensity from
      the lower to the higher energy peak.

PMID- 29051554
TI  - Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat
      Diet Fed Rodents.
AB  - ABSTACT: The gut hormone glucagon-like peptide (GLP)-1 and its analogues
      represent a new generation of anti-diabetic drugs, which have also demonstrated
      propensity to modulate host lipid metabolism. Despite this, drugs of this nature
      are currently limited to intramuscular administration routes due to intestinal
      degradation. The aim of this study was to design a recombinant microbial delivery
      vector for a GLP-1 analogue and assess the efficacy of the therapeutic in
      improving host glucose, lipid and cholesterol metabolism in diet induced obese
      rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC
      338 transformed to express a long-acting analogue of GLP-1 or the isogenic
      control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe
      intervention in rats reduced serum low-density lipoprotein cholesterol,
      triglycerides and triglyceride-rich lipoprotein cholesterol substantially.
      Conversely, extended GLP-1 microbe intervention improved glucose-dependent
      insulin secretion, glucose metabolism and cholesterol metabolism, compared to the
      high-fat control group. Interestingly, the microbe significantly attenuated the
      adiposity associated with the model and altered the serum lipidome, independently
      of GLP-1 secretion. These data indicate that recombinant incretin-secreting
      microbes may offer a novel and safe means of managing cholesterol metabolism and
      diet induced dyslipidaemia, as well as insulin sensitivity in metabolic
      dysfunction.

PMID- 29051556
TI  - Fabrication of a conjugated microporous polymer membrane and its application for
      membrane catalysis.
AB  - A flexible and free standing conjugated microporous polymer (CMP) membrane was
      prepared using a polyvinylpyrrolidone (PVP) electrospun membrane as a template.
      The PVP nanofibers of the template membrane were coated with a thin layer of the
      CMP through the in situ Sonogashira-Hagihara coupling reaction of 1,3,5
      triethynylbenzene and 1,4-diiodobenzene. The PVP nanofibers were removed by the
      solvent extraction to produce the CMP membrane, which retained the entangled
      fibrous structure of the template membrane. Each fiber showed a hollow tubular
      structure having a CMP wall with a thickness of tens of nanometers. The
      microporous polymer membrane exhibited a high BET surface area with hierarchical
      porosity and good permeability. As a catalytic CMP membrane, the Ag nanoparticle
      immobilized microporous polymer membrane was fabricated using an electrospun
      PVP@Ag membrane as a template. After being coated with the CMP, the PVP
      nanofibers were removed by the solvent extraction, but the Ag nanoparticles were
      trapped in the microporous polymer shell. The catalytic CMP membrane was
      successfully used for the catalytic reduction reaction of 4-nitrophenol. The
      hollow tubular structure and hierarchical porosity of the membrane allowed for
      the reactants to easily penetrate into the CMP wall and to contact the Ag
      nanoparticles, resulting in the high catalytic activity.

PMID- 29051555
TI  - The first characterized phage against a member of the ecologically important
      sphingomonads reveals high dissimilarity against all other known phages.
AB  - This study describes the first molecular characterization of a bacteriophage
      infecting a member of the environmentally important Sphingomonadaceae family.
      Both bacteriophage Lacusarx and its host Sphingobium sp. IP1 were isolated from
      activated sludge from a wastewater treatment plant. Genome sequencing revealed
      that the phage genes display little similarity to other known phages, despite a
      remarkable conservation of the synteny in which the functional genes occur among
      distantly related phages. Phylogenetic analyses confirmed that Lacusarx
      represents a hitherto undescribed genus of phages. A classical lysis cassette
      could not be identified in Lacusarx, suggesting that the genes encoding
      endolysin, holin, and spanin are host-specific and not found in phages infecting
      other bacteria. The virus harbors 24 tRNA genes corresponding to 18 different
      amino acids and furthermore has a significantly different codon usage than its
      host. Proteomic analysis of Lacusarx revealed the protein components of the phage
      particle. A lysogeny test indicated that Lacusarx is not a temperate phage.

PMID- 29051558
TI  - Pinned domain wall oscillator as a tuneable direct current spin wave emitter.
AB  - Local perturbations in the relative orientation of the magnetic moments in a
      continuous magnetic system can propagate in the form of waves. These so-called
      spin waves represent a promising candidate as an information carrier for spin
      based low-power applications. A localized, energy-efficient excitation of
      coherent and short-wavelength spin waves is a crucial technological requirement,
      and alternatives to excitation via the Oersted field of an alternating current
      must be explored. Here, we show how a domain wall pinned at a geometrical
      constriction in a perpendicularly magnetized thin nanowire emits spin waves when
      forced to rotate by the application of a low direct current flowing along the
      wire. Spin waves are excited by the in-plane stray field of the rotating domain
      wall and propagate at an odd harmonic of the domain wall rotation frequency in
      the direction of the electron's flow. The application of an external field,
      opposing domain wall depinning induced by the current, breaks the symmetry for
      spin wave propagation in the two domains, allowing emission in both directions
      but at different frequencies. The results presented define a new approach to
      manufacture tuneable high-frequency spin wave emitters of easy fabrication and
      low power consumption.

PMID- 29051557
TI  - Transforming growth factor-beta signaling pathway-associated genes SMAD2 and
      TGFBR2 are implicated in metabolic syndrome in a Taiwanese population.
AB  - The transforming growth factor-beta (TGF-beta) signaling pathway and its relevant
      genes have been correlated with an increased risk of developing various hallmarks
      of metabolic syndrome (MetS). In this study, we assessed whether the TGF-beta
      signaling pathway-associated genes of SMAD family member 2 (SMAD2), SMAD3, SMAD4,
      transforming growth factor beta 1 (TGFB1), TGFB2, TGFB3, transforming growth
      factor beta receptor 1 (TGFBR1), and TGFBR2 are associated with MetS and its
      individual components independently, through complex interactions, or both in a
      Taiwanese population. A total of 3,000 Taiwanese subjects from the Taiwan Biobank
      were assessed. Metabolic traits such as waist circumference, triglyceride, high
      density lipoprotein cholesterol, systolic and diastolic blood pressure, and
      fasting glucose were measured. Our results showed a significant association of
      MetS with the two single nucleotide polymorphisms (SNPs) of SMAD2 rs11082639 and
      TGFBR2 rs3773651. The association of MetS with these SNPs remained significant
      after performing Bonferroni correction. Moreover, we identified the effect of
      SMAD2 rs11082639 on high waist circumference. We also found that an interaction
      between the SMAD2 rs11082639 and TGFBR2 rs3773651 SNPs influenced MetS. Our
      findings indicated that the TGF-beta signaling pathway-associated genes of SMAD2
      and TGFBR2 may contribute to the risk of MetS independently and through gene-gene
      interactions.

PMID- 29051559
TI  - Comparative sphingolipidomics of disease-causing trypanosomatids reveal unique
      lifecycle- and taxonomy-specific lipid chemistries.
AB  - Trypanosomatids are parasitic protozoa which cause a spectrum of diseases,
      including trypanosomiasis and leishmaniasis, affecting millions of humans and
      animals worldwide. The surface of most protozoan parasites is heavily decorated
      with lipids and lipid-anchored molecules, forming protective barriers and acting
      as virulence factors during infection. Sphingolipids (SP) are major components of
      eukaryotic biomembranes, which play important roles in structural integrity,
      energy homeostasis and signaling. However, the precise chemical composition of SP
      in pathogens as well as their biochemical pathways and functions remain poorly
      characterized. Here, we present the first system-scale analyses of SP found in a
      panel of 7 trypanosomatids, including Leishmania donovani, Trypanosoma brucei and
      Trypanosoma cruzi. We characterized the structure of aminoethylphosphonate
      containing ceramides, which are found exclusively in stercorarian Trypanosoma.
      Employing the sensitive and semi-quantitative sphingolipidomics approach that we
      developed, we report the detection of over 300 molecular species of SP, and
      identified unique metabolic signatures which serve as discriminants of the
      pathogens based on their taxonomy and lifecycle stages. The deep sphingolipidome
      presented here is an important biochemical and technological resource for future
      works to dissect SP metabolism and functions in these medically and
      agriculturally relevant systems.

PMID- 29051560
TI  - Comprehensive profiling of lysine ubiquitome reveals diverse functions of lysine
      ubiquitination in common wheat.
AB  - Protein ubiquitination, which is a major post-translational modifications that
      occurs in eukaryotic cells, is involved in diverse biological processes. To date,
      large-scale profiling of the ubiquitome in common wheat has not been reported,
      despite its status as the major cereal crop in the world. Here, we performed the
      first ubiquitome analysis of the common wheat (Triticum aestivum L.) variety,
      Aikang 58. Overall, 433 lysine modification sites were identified in 285 proteins
      in wheat seedlings, and four putative ubiquitination motifs were revealed. In
      particular, 83 of the 285 ubiquitinated proteins had ubiquitination orthologs in
      Oryza sativa L., and Arabidopsis thaliana. Ubiquitylated lysines were found to
      have a significantly different preference for secondary structures when compared
      with the all lysines. In accordance with previous studies, proteins related to
      binding and catalytic activity were predicted to be the preferential targets of
      lysine ubiquitination. Besides, protein interaction network analysis reveals that
      diverse interactions are modulated by protein ubiquitination. Bioinformatics
      analysis revealed that the ubiquitinated proteins were involved in diverse
      biological processes. Our data provides a global view of the ubiquitome in common
      wheat for the first time and lays a foundation for exploring the physiological
      role of lysine ubiquitination in wheat and other plants.

PMID- 29051561
TI  - MAGT1-mediated disturbance of Mg2+ homeostasis lead to exhausted of HBV-infected
      NK and CD8+ T cells.
AB  - The magnesium transporter 1 (MAGT1) is a critical regulator of basal
      intracellular free magnesium ([Mg2+]i) levels. It has been shown that MAGT1 was
      involved in the disorder in Mg2+ homeostasis after Epstein-Barr virus (EBV)
      infection. Here, we identified the effects of MAGT1-mediated disturbance of Mg2+
      homeostasis on chronic hepatitis B virus (HBV)-infected natural killer (NK) and
      CD8+ T cells. The expression of MAGT1 was gradually decreased with the increase
      of infected time in CD8+ T cells, but not with that in NK cells, of the patients.
      Decreased level of intracellular free Mg2+ ([Mg2+]i) leads to defective
      expression of programmed cell death 1 (PD-1) and the NK activating receptor
      (NKG2D) in NK and CD8+ T cells. Our data illustrate that [Mg2+]i plays a key role
      in control of HBV infection.

PMID- 29051562
TI  - Motifs in the tau protein that control binding to microtubules and aggregation
      determine pathological effects.
AB  - Tau pathology is associated with cognitive decline in Alzheimer's disease, and
      missense tau mutations cause frontotemporal dementia. Hyperphosphorylation and
      misfolding of tau are considered critical steps leading to tauopathies. Here, we
      determine how motifs controlling conformational changes in the microtubule
      binding domain determine tau pathology in vivo. Human tau was overexpressed in
      the adult mouse forebrain to compare variants carrying residues that modulate tau
      propensity to acquire a beta-sheet conformation. The P301S mutation linked to
      frontotemporal dementia causes tau aggregation and rapidly progressing motor
      deficits. By comparison, wild-type tau becomes heavily hyperphosphorylated, and
      induces behavioral impairments that do not progress over time. However, the
      behavioral defects caused by wild-type tau can be suppressed when beta-sheet
      breaking proline residues are introduced in the microtubule-binding domain of
      tau. This modification facilitates tau interaction with microtubules, as shown by
      lower levels of phosphorylation, and by the enhanced protective effects of
      mutated tau against the severing of the cytoskeleton in neurons exposed to
      vinblastine. Altogether, motifs that are critical for tau conformation determine
      interaction with microtubules and subsequent pathological modifications,
      including phosphorylation and aggregation.

PMID- 29051563
TI  - Women's self-rated attraction to male faces does not correspond with
      physiological arousal.
AB  - There has been little work to determine whether attractiveness ratings of faces
      correspond to sexual or more general attraction. We tested whether a measure of
      women's physiological arousal (pupil diameter change) was correlated with ratings
      of men's facial attractiveness. In Study 1, women rated the faces of men for whom
      we also measured salivary testosterone. They rated each face for attractiveness,
      and for desirability for friendship and long- and short-term romantic
      relationships. Pupil diameter change was not related to subjective ratings of
      attractiveness, but was positively correlated with the men's testosterone. In
      Study 2 we compared women's pupil diameter change in response to the faces of men
      with high versus low testosterone, as well as in response to non-facial images
      pre-rated as either sexually arousing or threatening. Pupil dilation was not
      affected by testosterone, and increased relatively more in response to sexually
      arousing than threatening images. We conclude that self-rated preferences may not
      provide a straightforward and direct assessment of sexual attraction. We argue
      that future work should identify the constructs that are tapped via
      attractiveness ratings of faces, and support the development of methodology which
      assesses objective sexual attraction.

PMID- 29051564
TI  - Network analysis of EMT and MET micro-RNA regulation in breast cancer.
AB  - Over the last years, microRNAs (miRs) have shown to be crucial for breast tumour
      establishment and progression. To understand the influence that miRs have over
      transcriptional regulation in breast cancer, we constructed mutual information
      networks from 86 TCGA matched breast invasive carcinoma and control tissue RNA
      Seq and miRNA-Seq sequencing data. We show that miRs are determinant for tumour
      and control data network structure. In tumour data network, miR-200, miR-199 and
      neighbour miRs seem to cooperate on the regulation of the acquisition of
      epithelial and mesenchymal traits by the biological processes: Epithelial
      Mesenchymal Transition (EMT) and Mesenchymal to Epithelial Transition (MET).
      Despite structural differences between tumour and control networks, we found a
      conserved set of associations between miR-200 family members and genes such as
      VIM, ZEB-1/2 and TWIST-1/2. Further, a large number of miRs observed in tumour
      network mapped to a specific chromosomal location in DLK1-DIO3 (Chr14q32); some
      of those miRs have also been associated with EMT and MET regulation. Pathways
      related to EMT and TGF-beta reinforce the relevance of miR-200, miR-199 and DLK1
      DIO3 cluster in breast cancer. With this approach, we stress that miR inclusion
      in gene regulatory network construction improves our understanding of the
      regulatory mechanisms underlying breast cancer biology.

PMID- 29051566
TI  - Characterization of old RHDV strains by complete genome sequencing identifies a
      novel genetic group.
AB  - Rabbit hemorrhagic disease (RHD) is a veterinary disease that affects the
      European rabbit and has a significant economic and ecological negative impact. In
      Portugal, rabbit hemorrhagic disease virus (RHDV) was reported in 1989 and still
      causes enzootic outbreaks. Several recombination events have been detected in
      RHDV strains, including in the first reported outbreak. Here we describe the
      occurrence of recombination in RHDV strains recovered from rabbit and Iberian
      hare samples collected in the mid-1990s in Portugal. Characterization of full
      genomic sequences revealed the existence of a single recombination breakpoint at
      the boundary of the non-structural and the structural encoding regions, further
      supporting the importance of this region as a recombination hotspot in
      lagoviruses. Phylogenetic analysis showed that in the structural region, the
      recombinant strains were similar to pathogenic G1 strains, but in the non
      structural region they formed a new group that diverged ~13% from known strains.
      No further reports of such group exist, but this recombination event was also
      detected in an Iberian hare that was associated with the earliest species jump in
      RHDV. Our results highlight the importance of the characterization of full
      genomes to disclose RHDV evolution and show that lagoviruses' diversity has been
      significantly undersampled.

PMID- 29051565
TI  - Control of enzyme reactions by a reconfigurable DNA nanovault.
AB  - Biological systems use compartmentalisation as a general strategy to control
      enzymatic reactions by precisely regulating enzyme-substrate interactions. With
      the advent of DNA nanotechnology, it has become possible to rationally design DNA
      based nano-containers with programmable structural and dynamic properties. These
      DNA nanostructures have been used to cage enzymes, but control over enzyme
      substrate interactions using a dynamic DNA nanostructure has not been achieved
      yet. Here we introduce a DNA origami device that functions as a nanoscale vault:
      an enzyme is loaded in an isolated cavity and the access to free substrate
      molecules is controlled by a multi-lock mechanism. The DNA vault is characterised
      for features such as reversible opening/closing, cargo loading and wall porosity,
      and is shown to control the enzymatic reaction catalysed by an encapsulated
      protease. The DNA vault represents a general concept to control enzyme-substrate
      interactions by inducing conformational changes in a rationally designed DNA
      nanodevice.

PMID- 29051567
TI  - Mesenchymal stem/stromal cells enhance engraftment, vasculogenic and pro
      angiogenic activities of endothelial colony forming cells in immunocompetent
      hosts.
AB  - The clinical use of endothelial colony forming cells (ECFC) is hampered by their
      restricted engraftment. We aimed to assess engraftment, vasculogenic and pro
      angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient
      (rag1 -/- C57BL/6: Rag1) mice. In addition, the impact of host immune system was
      investigated where ECFC were co-implanted with mesenchymal stem/stromal cells
      (MSC) from adult bone marrow (AdBM-MSC), fetal bone marrow (fBM-MSC), fetal
      placental (fPL-MSC), or maternal placental (MPL-MSC). Transplantation of ECFCs in
      Matrigel plugs resulted in less cell engraftment in WT mice compared to Rag1
      mice. Co-implantation with different MSCs resulted in a significant increase in
      cell engraftment up to 9 fold in WT mice reaching levels of engraftment observed
      when using ECFCs alone in Rag1 mice but well below levels of engraftment with MSC
      ECFC combination in Rag1 recipients. Furthermore, MSCs did not reduce murine
      splenic T cell proliferation in response to ECFCs in vitro. ECFCs enhanced the
      murine neo-vascularization through paracrine effect, but with no difference
      between Rag1 and WT mice. In conclusions, the host adaptive immune system affects
      the engraftment of ECFCs. MSC co-implantation improves ECFC engraftment and
      function even in immunocompetent hosts mostly through non-immune mechanisms.

PMID- 29051568
TI  - Synchrotron radiation circular dichroism spectroscopy reveals structural
      divergences in HDL-bound apoA-I variants.
AB  - Apolipoprotein A-I (apoA-I) in high-density lipoprotein (HDL) provides
      cardiovascular protection. Synchrotron radiation circular dichroism (SRCD)
      spectroscopy was used to analyze the dynamic solution structure of the apoA-I
      protein in the apo- and HDL-states and the protein structure conversion in HDL
      formation. Wild-type apoA-I protein was compared to human variants that either
      are protective (R173C, Milano) or lead to increased risk for ischaemic heart
      disease (A164S). Comparable secondary structure distributions in the HDL
      particles, including significant levels of beta strand/turn, were observed. ApoA
      I Milano in HDL displayed larger size heterogeneity, increased protein
      flexibility, and an altered lipid-binding profile, whereas the apoA-I A164S in
      HDL showed decrease thermal stability, potentially linking the intrinsic HDL
      propensities of the variants to disease risk.

PMID- 29051569
TI  - The additive effects of atorvastatin and insulin on renal function and renal
      organic anion transporter 3 function in diabetic rats.
AB  - Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3
      hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are
      widely used as cholesterol-lowering medication with several "pleiotropic" effects
      in diabetic patients. This study aims to evaluate whether the protective effects
      of atorvastatin and insulin on renal function and renal organic anion transporter
      3 (Oat3) function involve the modulation of oxidative stress and pancreatic
      function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal
      injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or
      combined treatment were given for 4 weeks after diabetic condition had been
      confirmed. Diabetic rats demonstrated renal function and renal Oat3 function
      impairment with an increased MDA level and decreased SOD protein expression
      concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin
      plus atorvastatin (combined) treatment effectively restored renal function as
      well as renal Oat3 function which correlated with the decrease in hyperglycemia
      and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic
      rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin
      plus insulin seems to exert the additive effect in improving renal functionby
      alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and
      apoptosis.

PMID- 29051570
TI  - Prediction of recurrence in early stage non-small cell lung cancer using computer
      extracted nuclear features from digital H&E images.
AB  - Identification of patients with early stage non-small cell lung cancer (NSCLC)
      with high risk of recurrence could help identify patients who would receive
      additional benefit from adjuvant therapy. In this work, we present a
      computational histomorphometric image classifier using nuclear orientation,
      texture, shape, and tumor architecture to predict disease recurrence in early
      stage NSCLC from digitized H&E tissue microarray (TMA) slides. Using a
      retrospective cohort of early stage NSCLC patients (Cohort #1, n = 70), we
      constructed a supervised classification model involving the most predictive
      features associated with disease recurrence. This model was then validated on two
      independent sets of early stage NSCLC patients, Cohort #2 (n = 119) and Cohort #3
      (n = 116). The model yielded an accuracy of 81% for prediction of recurrence in
      the training Cohort #1, 82% and 75% in the validation Cohorts #2 and #3
      respectively. A multivariable Cox proportional hazard model of Cohort #2,
      incorporating gender and traditional prognostic variables such as nodal status
      and stage indicated that the computer extracted histomorphometric score was an
      independent prognostic factor (hazard ratio = 20.81, 95% CI: 6.42-67.52, P <
      0.001).

PMID- 29051572
TI  - Marine self-potential survey for exploring seafloor hydrothermal ore deposits.
AB  - We conducted a self-potential survey at an active hydrothermal field, the Izena
      hole in the mid-Okinawa Trough, southern Japan. This field is known to contain
      Kuroko-type massive sulphide deposits. This survey measured the self-potential
      continuously in ambient seawater using a deep-tow array, which comprises an
      electrode array with a 30-m-long elastic rod and a stand-alone data acquisition
      unit. We observed negative self-potential signals not only above active
      hydrothermal vents and visible sulphide mounds but also above the flat seafloor
      without such structures. Some signals were detectable >50 m above the seafloor.
      Analysis of the acquired data revealed these signals' source as below the
      seafloor, which suggests that the self-potential method can detect hydrothermal
      ore deposits effectively. The self-potential survey, an easily performed method
      for initial surveys, can identify individual sulphide deposits from a vast
      hydrothermal area.

PMID- 29051571
TI  - A new cellular type in invertebrates: first evidence of telocytes in leech Hirudo
      medicinalis.
AB  - Telocytes, a peculiar cell type, were recently found in vertebrates. Hence this
      cell system has been reported as ubiquitous in the bodies of mammals and
      interpreted as an important player in innate immunity and tissue regeneration, it
      is reasonable to look for it also in invertebrates, that rely their integrity
      solely by innate immunity. Here we describe, at morphological and functional
      level, invertebrate telocytes from the body of leech Hirudo medicinalis
      (Annelida), suggesting how these cells, forming a resident stromal 3D network,
      can influence or participate in different events. These findings support the
      concepts that leech telocytes: i) are organized in a cellular dynamic and
      versatile 3D network likewise the vertebrate counterpart; ii) are an
      evolutionarily conserved immune-neuroendocrine system; iii) form an immuno
      surveillance system of resident cells responding faster than migrating
      immunocytes recruited in stimulated area; iv) communicate with neighbouring cells
      directly and indirectly, via cell-cell contacts and soluble molecules secreted by
      multivesicular bodies; v) present within neo-vessels, share with immunocytes the
      mesodermal lineage; vi) are involved in regenerative processes. In conclusion, we
      propose that HmTCs, integrating so different functions, might explain the innate
      immune memory and can be associated with several aged related diseases.

PMID- 29051573
TI  - Nucleation and annihilation of skyrmions in Mn2CoAl observed through the
      topological Hall effect.
AB  - Magnetic skyrmions are topologically protected spin textures with great
      technological potential. These topologically non-trivial non-coplanar spin
      textures give rise to a topological Hall effect, enabling the purely electronic
      detection of magnetic skyrmions. We report a clear topological Hall effect in
      thin films of the the Heusler alloy Mn2CoAl, a ferromagnetic spin-gapless
      semiconductor, capped by a thin layer of Pd. We exploit the strong thickness- and
      temperature-dependence of the anomalous Hall effect in this system, tuning it to
      zero to enable the unambiguous measurement of the topological Hall effect, which
      is observed for temperatures between 3 K and 280 K. The topological Hall effect
      is evidence of skyrmions, and we demonstrate the simultaneous coexistence of
      opposite polarity skyrmions using a novel method involving minor field loops of
      the Hall effect.

PMID- 29051574
TI  - Florfenicol-induced Mitochondrial Dysfunction Suppresses Cell Proliferation and
      Autophagy in Fibroblasts.
AB  - Florfenicol (FLO) is one of the most popular antibiotics used in veterinary
      clinic and aquaculture. FLO can inhibit both bacterial and mitochondrial protein
      synthesis. However, the effects of FLO on mitochondrial function and cellular
      homeostasis remain unclear. Here we show that FLO inhibits expression of
      mitochondrial DNA-encoded proteins, decreases mitochondrial membrane potential,
      and promotes generation of reactive oxygen species (ROS) in vitro. As a result,
      activities of mitochondrial respiratory chain complex I and IV and the cellular
      ATP level are decreased and mitochondrial morphology is damaged. FLO represses
      cell growth and proliferation by suppression of phosphorylation of p70S6K through
      AMPK/mTOR/p70S6K pathway. Furthermore, FLO also induces G0/G1 cell cycle arrest
      via increase of p21 levels through activating ROS/p53/p21 pathway. Moreover, the
      clearance of damaged mitochondria by autophagy is impaired, leading to cell
      proliferation inhibition and promotes cell senescence. In addition, FLO-induced
      upregulation of cytosolic p53 may contribute to mitophagy deficiency via
      regulation of Parkin recruitment. In summary, our data suggest that florfenicol
      is an inhibitor of mitochondrial protein synthesis that can induce noticeable
      cytotoxicity. Thus, these findings can be useful for guiding the proper use of
      FLO and the development of safe drugs.

PMID- 29051575
TI  - Substrate recognition by two different P450s: Evidence for conserved roles in a
      common fold.
AB  - Cytochrome P450 monooxygenases CYP101A1 and MycG catalyze regio- and
      stereospecific oxidations of their respective substrates, d-camphor and
      mycinamicin IV. Despite the low sequence homology between the two enzymes (29%
      identity) and differences in size and hydrophobicity of their substrates, the
      conformational changes that occur upon substrate binding in both enzymes as
      determined by solution NMR methods show some striking similarities. Many of the
      same secondary structural features in both enzymes are perturbed, suggesting the
      existence of a common mechanism for substrate binding and recognition in the P450
      superfamily.

PMID- 29051576
TI  - Decreasing Bacillus thuringiensis israelensis sensitivity of Chironomus riparius
      larvae with age indicates potential environmental risk for mosquito control.
AB  - Mosquito control based on the use of Bacillus thuringiensis israelensis (Bti) is
      regarded as an environmental friendly method. However, Bti also affects non
      target chironomid midges that are recognized as a central resource in wetland
      food webs. To evaluate the risk for different larval stages of Chironomus
      riparius we performed a test series of daily acute toxicity laboratory tests
      following OECD guideline 235 over the entire aquatic life cycle of 28 days. Our
      study is the first approach that performs an OECD approved test design with Bti
      and C. riparius as a standard organism in ecotoxicological testing. First-instar
      larvae of Chironomus riparius show an increased sensitivity towards Bti which is
      two orders of magnitude higher than for fourth instar larvae. Most EC50 values
      described in the literature are based on acute toxicity tests using third and
      fourth instar larvae. The risk for chironomids is underestimated when applying
      the criteria of the biocide regulation EU 528/2012 to our data and therefore the
      existing assessment approval is not protective. Possible impacts of Bti induced
      changes in chironomid abundances and community composition may additionally
      affect organisms at higher trophic levels, especially in spring when chironomid
      midges represent a key food source for reproducing vertebrates.

PMID- 29051577
TI  - De novo mutations of TUBA3D are associated with keratoconus.
AB  - Keratoconus (KC) is a common degenerative corneal disease, and heredity plays a
      key role in its development. Although few genes are known to cause KC, a large
      proportion of disease-causing genes remain to be revealed. Here, we report the
      identification of TUBA3D as a novel gene linked to KC. Using whole-exome
      sequencing of a twins pedigree, a novel de novo mutation (c.31 C > T,
      p.Gln11stop) in TUBA3D gene was identified. A screening performed in 200
      additional unrelated patients with KC revealed another two mutations (c.201insTT,
      p.Val68Leufs*2; c.*2 G > A) in two patients. TUBA3D was expressed highly in the
      cornea, and the twins had lower TUBA3D expression and higher UPA and MMP1
      expressions than the normal parents. Through function prediction and in vitro
      cell experiment, we further demonstrated that the mutant proteins of TUBA3D were
      unstable and could lead to human corneal fibroblast cells performing higher MMPs
      expression and oxidative stress. These changes thus reduce the amount of
      extracellular matrices within corneas and undoubtedly play a major role in
      stromal thinning, which is characteristic of KC corneas. Our study showed that
      TUBA3D is a new gene that causes KC, thus supporting the evidence that this
      protein has an additional function into the human cornea.

PMID- 29051578
TI  - Associations of Blood Pressure with the Factors among Adults in Jilin Province: A
      Cross-Sectional Study Using Quantile Regression Analysis.
AB  - Hypertension has become a major public health challenge. However, numerous
      research results reported in the literature focus primarily on risk factors of
      hypertension, little is known about how the whole continuum of blood pressure
      (BP) is associated with risk factors of hypertension. This study aims to reveal
      quantile-specific associations of BP with its risk factors. A cross-sectional
      survey based on a sample of 23,050 adults aged 18 to 79 years was conducted in
      Jilin Province in 2012, and some subjects were excluded due to missing values in
      BP or having BP control according to the purpose of this study. Quantile
      regression (QR) was employed to investigate the associations between
      systolic/diastolic blood pressure (SBP/DBP) and the risk factors. The SBP and DBP
      in males presented statistically higher than females (P < 0.001). High-salt diet
      for males manifested a slightly increasing positive association with higher SBP
      only for high quantiles (>=70), but with a higher DBP for middle part of the
      quantiles (30~75), compared with bland diet. High-salt diet, drinking and high
      density lipoprotein cholesterol (HDL-C) were positively associated with BP
      measures in males. And the coefficient of total cholesterol (TC) in QR increased
      with BP in females who used to live in town.

PMID- 29051579
TI  - Myocardial metabolic alterations in mice with diet-induced atherosclerosis:
      linking sulfur amino acid and lipid metabolism.
AB  - Atherosclerosis is a leading cause of cardiovascular disease (CVD), but the
      effect of diet on the atherosclerotic heart's metabolism is unclear. We used an
      integrated metabolomics and lipidomics approach to evaluate metabolic
      perturbations in heart and serum from mice fed an atherogenic diet (AD) for 8,
      16, and 25 weeks. Nuclear magnetic resonance (NMR)-based metabolomics revealed
      significant changes in sulfur amino acid (SAA) and lipid metabolism in heart from
      AD mice compared with heart from normal diet mice. Higher SAA levels in AD mice
      were quantitatively verified using liquid chromatography-mass spectrometry
      (LC/MS). Lipidomic profiling revealed that fatty acid and triglyceride (TG)
      levels in the AD group were altered depending on the degree of unsaturation.
      Additionally, levels of SCD1, SREBP-1, and PPARgamma were reduced in AD mice
      after 25 weeks, while levels of reactive oxygen species were elevated. The
      results suggest that a long-term AD leads to SAA metabolism dysregulation and
      increased oxidative stress in the heart, causing SCD1 activity suppression and
      accumulation of toxic TGs with a low degree of unsaturation. These findings
      demonstrate that the SAA metabolic pathway is a promising therapeutic target for
      CVD treatment and that metabolomics can be used to investigate the metabolic
      signature of atherosclerosis.

PMID- 29051580
TI  - Novel cycloneolignans from Vernicia fordii with inhibitory effects on over
      activation of BV2 cells in vitro.
AB  - Novel natural products 7R, 8R, 7'R, 9'S-verniciasin A (1a), 7S, 8S, 7'S, 9'R-
      verniciasin A (1b), 7R, 8R, 7'R, 9'S-7'-methoxylverniciasin A (2a) and 7S, 8S,
      7'S, 9'R-7'-methoxylverniciasin A (2b) were characterized from the seed capsule
      of Vernicia fordii. And the unique 9-O-9'-7, 9'-cyclo-8, 1'-neolignan skeleton
      with a seven-membered ring, was identified by extensive spectroscopic analysis.
      Further the possible biosynthetic pathway was briefly discussed. Interestingly,
      1a, 2a, 1b and 2b all exhibited significant stereoselective inhibitory effects on
      NO production in LPS-induced BV2 microglia cell. Then the primary mechanism of
      the bioactivities and stereoselectivity was explored by means of bioassay and
      molecular docking.

PMID- 29051581
TI  - Blue carbon stores in tropical seagrass meadows maintained under green turtle
      grazing.
AB  - Seagrass meadows are important sites for carbon storage. Green turtles (Chelonia
      mydas) are marine megaherbivores that consume seagrass throughout much of their
      global range. With successful conservation efforts, turtle abundance will
      increase, leading to more meadows being returned to their natural grazed state.
      There is concern this may lead to a loss of carbon stored in these systems, but
      the effects of green turtle grazing on seagrass ecosystem carbon dynamics have
      not been investigated. Here we experimentally show that despite 79% lower net
      ecosystem production (NEP) following grazing (24.7 vs. 119.5 mmol C m-2 d-1) in a
      Caribbean Thalassia testudinum seagrass meadow, grazed areas maintained net
      positive metabolic carbon uptake. Additionally, grazing did not change the meadow
      production to respiration ratio, indicating it did not stimulate remineralization
      of sediment carbon stores. Compared to other published estimates of seagrass NEP
      (median: 20.6 mmol C m-2 d-1), NEP in grazed Caribbean T. testudinum meadows is
      similar to that in many other ungrazed systems. Our results demonstrate that
      while grazing does decrease potential future carbon sequestration as a result of
      lower NEP, it does not promote a metabolic release of current carbon stocks.

PMID- 29051582
TI  - A role for the purinergic receptor P2X3 in astrocytes in the mechanism of
      craniofacial neuropathic pain.
AB  - The purinergic receptor P2X3, expressed in the central terminals of primary
      nociceptive neurons in the brainstem, plays an important role in pathological
      pain. However, little is known about expression of P2X3 in the brainstem
      astrocytes and its involvement in craniofacial pathologic pain. To address this
      issue, we investigated the expression of P2X3 in astrocytes in the trigeminal
      caudal nucleus (Vc) in a rat model of craniofacial neuropathic pain, chronic
      constriction injury of infraorbital nerve (CCI-ION). We found that 1) P2X3
      immunoreactivity is observed in the brainstem astrocytes, preferentially in their
      fine processes, 2) the number of P2X3-positive fine astrocytic processes and the
      density of P2X3 in these processes were increased significantly in CCI-ION rats,
      compared to control rats, and 3) administration of MPEP, a specific mGluR5
      antagonist, alleviated the mechanical allodynia and abolished the increase in
      density of P2X3 in fine astrocytic processes caused by CCI-ION. These findings
      reveal preferential expression of P2X3 in the fine astrocytic processes in the
      brainstem, propose a novel role of P2X3 in the fine astrocytic process in the
      mechanism of craniofacial neuropathic pain, and suggest that the expression of
      astrocytic P2X3 may be regulated by astrocytic mGluR5.

PMID- 29051584
TI  - Radiation-induced resistance oscillations in 2D electron systems with strong
      Rashba coupling.
AB  - We present a theoretical study on the effect of radiation on the
      mangetoresistance of two-dimensional electron systems with strong Rashba spint
      orbit coupling. We want to study the interplay between two well-known effects in
      these electron systems: the radiation-induced resistance oscillations and the
      typical beating pattern of systems with intense Rashba interaction. We
      analytically derive an exact solution for the electron wave function
      corresponding to a total Hamiltonian with Rashba and radiation terms. We consider
      a perturbation treatment for elastic scattering due to charged impurities to
      finally obtain the magnetoresistance of the system. Without radiation we recover
      a beating pattern in the amplitude of the Shubnikov de Hass oscillations: a set
      of nodes and antinodes in the magnetoresistance. In the presence of radiation
      this beating pattern is strongly modified following the profile of radiation
      induced magnetoresistance oscillations. We study their dependence on intensity
      and frequency of radiation, including the teraherzt regime. The obtained results
      could be of interest for magnetotransport of nonideal Dirac fermions in 3D
      topological insulators subjected to radiation.

PMID- 29051583
TI  - Nuclear fragments of the neural cell adhesion molecule NCAM with or without
      polysialic acid differentially regulate gene expression.
AB  - The neural cell adhesion molecule (NCAM) is the major carrier of polysialic acid
      (PSA) which modulates NCAM functions of neural cells at the cell surface. In
      previous studies, we have shown that stimulation of cultured neurons with
      surrogate NCAM ligands leads to the generation and nuclear import of PSA-lacking
      and -carrying NCAM fragments. Here, we show that the nuclear import of the PSA
      carrying NCAM fragment is mediated by positive cofactor 4 and cofilin, which we
      identified as novel PSA-binding proteins. In the nucleus, the PSA-carrying NCAM
      fragment interacts via PSA with PC4 and cofilin, which are involved in RNA
      polymerase II-dependent transcription. Microarray analysis revealed that the
      nuclear PSA-carrying and -lacking NCAM fragments affect expression of different
      genes. By qPCR and immunoblot analysis we verified that the nuclear PSA-carrying
      NCAM fragment increases mRNA and protein expression of nuclear receptor subfamily
      2 group F member 6, whereas the PSA-lacking NCAM fragment increases mRNA and
      protein expression of low density lipoprotein receptor-related protein 2 and
      alpha-synuclein. Differential gene expression evoked by nuclear NCAM fragments
      without and with PSA indicates that PSA-carrying and -lacking NCAM play different
      functional roles in the nervous system.

PMID- 29051585
TI  - MiR-200c regulates tumor growth and chemosensitivity to cisplatin in osteosarcoma
      by targeting AKT2.
AB  - MicroRNAs (miRNAs) expression aberration has been discovered in almost all human
      cancers, thus offering a group of potential diagnostic markers, prognostic
      factors and therapeutic targets in tumorigenesis. Now our data showed that miR
      200c, which is downregulated in osteosarcoma tissues, drives chemosensitivity to
      cisplatin in osteosarcoma. We demonstrated that AKT2 is a direct target of miR
      200c, Spearman's rank correlation analysis showed that the expression levels of
      AKT2 and miR-200c in 35 pairs of osteosarcoma specimens were inversely
      correlated. Moreover, miR-200c inhibited cell proliferation and cell migration.
      Taken together, for the first time, our results demonstrate that miR-200c plays a
      significant role in osteosarcoma tumor growth and chemosensitivity by regulating
      AKT2, which may provide a novel therapeutic strategy for treatment of
      osteosarcoma.

PMID- 29051586
TI  - Phosphatidylserine-Induced Conformational Modulation of Immune Cell Exhaustion
      Associated Receptor TIM3.
AB  - In the face of chronic cancers and protracted viral infections, human immune
      cells are known to adopt an exhausted state in which their effector functions are
      lost. In recent years, a number of inhibitory receptors have been connected to
      the immune cell exhaustion phenotype; furthermore, ligands capable of activating
      these receptors have been discovered. The molecular mechanisms by which these
      ligands affect the exhausted states of immune cells, however, are largely
      unknown. Here, we present the results of molecular dynamics simulations of one
      potential exhaustion-associated system: the complex of human inhibitory receptor
      TIM3 (hTIM3) and its ligand phosphatidylserine (PSF). We find that PSF
      fundamentally alters the electrostatic environment within hTIM3's Ca2+ binding
      site, facilitating the formation of a salt bridge and freeing a tyrosine
      containing strand. This liberated tyrosine then collapses into a nearby
      hydrophobic pocket, anchoring a modified conformational ensemble typified by a
      beta-strand rearrangement. The "electrostatic switching/hydrophobic anchoring"
      mechanism of conformational modulation reported here suggests a new type of
      process by which TIM3 activation might be achieved. This work also highlights
      strategies by which PSF-mediated conformational change could be controlled,
      either through administration of small molecules, execution of mutations, or
      modification of receptor phosphorylation states.

PMID- 29051587
TI  - DNA methylation and hydroxymethylation analyses of the active LINE-1 subfamilies
      in mice.
AB  - Retrotransposon long interspersed nuclear element-1 (LINE-1) occupies a large
      proportion of the mammalian genome, comprising approximately 100,000 genomic
      copies in mice. Epigenetic status of the 5' untranslated region (5'-UTR) of LINE
      1 is critical for its promoter activity. DNA methylation levels in the 5'-UTR of
      human active LINE-1 subfamily can be measured by well-established methods, such
      as a pyrosequencing-based assay. However, because of the considerable sequence
      and structural diversity in LINE-1 among species, methods for such assays should
      be adapted for the species of interest. Here we developed pyrosequencing-based
      assays to examine methylcytosine (mC) and hydroxymethylcytosine (hmC) levels of
      the three active LINE-1 subfamilies in mice (TfI, A, and GfII). Using these
      assays, we quantified mC and hmC levels in four brain regions and four nonbrain
      tissues including tail, heart, testis, and ovary. We observed tissue- and
      subfamily-specific mC and hmC differences. We also found that mC levels were
      strongly correlated among different brain regions, but mC levels of the testis
      showed a poor correlation with those of other tissues. Interestingly, mC levels
      in the A and GfII subfamilies were highly correlated, possibly reflecting their
      close evolutionary relationship. Our assays will be useful for exploring the
      epigenetic regulation of the active LINE-1 subfamilies in mice.

PMID- 29051588
TI  - Exceptional 20th century glaciological regime of a major SE Greenland outlet
      glacier.
AB  - The early 2000s accelerated ice-mass loss from large outlet glaciers in W and SE
      Greenland has been linked to warming of the subpolar North Atlantic. To
      investigate the uniqueness of this event, we extend the record of glacier and
      ocean changes back 1700 years by analyzing a sediment core from Sermilik Fjord
      near Helheim Glacier in SE Greenland. We show that multidecadal to centennial
      increases in alkenone-inferred Atlantic Water SSTs on the shelf occurred at times
      of reduced solar activity during the Little Ice Age, when the subpolar gyre
      weakened and shifted westward promoted by atmospheric blocking events. Helheim
      Glacier responded to many of these episodes with increased calving, but despite
      earlier multidecadal warming episodes matching the 20th century high SSTs in
      magnitude, the glacier behaved differently during the 20th century. We suggest
      the presence of a floating ice tongue since at least 300 AD lasting until 1900 AD
      followed by elevated 20th century glacier calving due to the loss of the tongue.
      We attribute this regime shift to 20th century unprecedented low sea-ice
      occurrence in the East Greenland Current and conclude that properties of this
      current are important for the stability of the present ice tongues in NE
      Greenland.

PMID- 29051589
TI  - Autophagy induces apoptosis and death of T lymphocytes in the spleen of pigs
      infected with CSFV.
AB  - Lymphocyte depletion and immunosuppression are typical clinical characteristics
      of pigs infected with classical swine fever virus (CSFV). The apoptosis of virus
      infected and bystander cells plays a role in the immunopathology of classical
      swine fever (CSF). Here, we offer the first evidence that autophagy is involved
      in apoptosis and death of T lymphocytes in the spleen of pigs infected with CSFV.
      Using immunohistochemical assays, we observed that more LC3II-positive cells
      appear in the T-cell zone of spleens. Spleen cell apoptosis was demonstrated
      using flow cytometry and TUNEL staining. Confocal immunofluorescence revealed
      that partial LC3II-positive cells were simultaneously TUNEL-positive. By
      cultivating spleen cells ex vivo, we demonstrated that the inhibition of
      autophagy by 3-MA treatment inhibited apoptosis and death of T lymphocytes caused
      by CSFV infection but did not have this effect  on B lymphocytes. Further
      observations demonstrated that uninfected cells in the spleen were also
      undergoing autophagy in vivo. In summary, these results linked autophagy with the
      apoptosis and cell death of splenic T cells, providing a new outlook to
      understand the mechanism of T lymphocyte depletion and immunosuppression during
      CSF.

PMID- 29051590
TI  - Association between corneal endothelial cell densities and elevated cytokine
      levels in the aqueous humor.
AB  - Annual reduction rate of corneal endothelial cell density (ECD) varies among
      etiologies, however, the cause of chronic endothelial cell loss is still unknown.
      We recently reported the elevation of inflammatory cytokines in the aqueous humor
      (AqH) in eyes with bullous keratopathy and low ECD. To evaluate the association
      between ECD and aqueous cytokine levels, we collected a total of 157 AqH samples
      prospectively. The AqH levels of cytokines were measured and multivariate
      analyses were conducted to find the correlation between ECD, aqueous cytokine
      levels and clinical factors, such as number of previous intraocular surgeries and
      protein concentration in AqH. As a result, ECD was negatively correlated with
      specific cytokine levels, including IL-1alpha, IL-4, IL-13, MIP-1beta, TNF-alpha
      and E-selectin (all P < 0.05). The aqueous cytokine levels showed different
      correlations with these clinical factors; the number of previous intraocular
      surgeries was associated with all cytokines except MIP-1alpha. The AqH protein
      concentration and the status of intraocular lens showed similar patterns of
      elevation of IL-1alpha, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, MIP-1beta, MCP-1,
      E-selectin, P-selectin and sICAM-1. In conclusion, elevation of AqH cytokine
      levels was associated with reduced ECDs. AqH cytokine levels showed significant
      correlations with clinical factors associated with low ECDs.

PMID- 29051591
TI  - Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk
      in an age-related manner: A systematic review and meta-analysis.
AB  - G20210A polymorphism (rs1799963) within the prothrombin gene is associated with a
      higher circulation level of prothrombin, thus increasing the likelihood of
      developing myocardial infarction (MI). Opinions differ regarding the correlation
      between prothrombin G20210A genotype and MI risk, which prompted us to conduct a
      meta-analysis to determine this association. PubMed, EMBASE, Web of Science and
      CNKI were searched for pertinent reports. A total of 34 studies involving 14 611
      MI cases and 84 358 controls were analyzed in this quantitative analysis. We
      found a statistically significant association between prothrombin G20210A
      polymorphism and MI in the allele model (A vs. G, OR = 1.43, 95%CI: 1.18-1.72),
      heterozygote model (GA vs. GG, OR = 1.41, 95%CI: 1.16-1.72) and dominant model
      (GA + AA vs. GG, OR = 1.41, 95%CI: 1.15-1.72). The association remains
      significant in Caucasians but not in non-Caucasians. Moreover, prothrombin
      G20210A polymorphism increases MI risk in an age-related manner. A further
      significant association was found in a subpopulation younger than 55 years
      (allele model, OR = 1.76, 95%CI: 1.32-2.35; heterozygote model, OR = 1.70, 95%CI:
      1.24-2.33; dominant model, OR = 1.70, 95%CI: 1.24-2.34). Sensitivity analysis and
      publication bias analysis revealed stable and statistically robust results. Our
      meta-analysis demonstrated that prothrombin G20210A polymorphism may represent a
      risk factor for MI.

PMID- 29051592
TI  - All Dielectric Transmissive Structural Multicolor Pixel Incorporating a Resonant
      Grating in Hydrogenated Amorphous Silicon.
AB  - All dielectric transmissive type polarization-tuned structural multicolor pixels
      (MCPs) are proposed and demonstrated based on a one-dimensional hydrogenated
      amorphous silicon (a-Si:H) grating integrated with a silicon nitride waveguide.
      Both bandpass and bandstop transmission filtering characteristics in the visible
      regime, centered at the same wavelength, have been achieved by tailoring the
      structural parameters including the duty ratio of the grating and the thickness
      of the dielectric waveguide. For the three manufactured MCPs, the transmission
      peak exceeds 70% for the transverse electric (TE) polarization and 90% for the
      transverse magnetic (TM) polarization as observed at the resonance and off
      resonance wavelength, respectively. The polarization-switched transmissions are
      attributed to the guided mode resonance initiated by the interaction of the a
      Si:H grating and the dielectric waveguide. A broad color palette covering the
      entire visible band was successfully realized from a suite of MCPs with varying
      grating pitches. The proposed structural color pixels are expected to facilitate
      the construction of dynamic displays, image sensors, optical data storage,
      security tags, and so forth.

PMID- 29051593
TI  - Creating single Majorana type topological zero mode in superfluids of cold
      fermionic atoms.
AB  - We explore the topological phase, which involves Majorana type topological zero
      mode fermions (MTZFs) at the edge, using d-wave superfluid with Rashba spin-orbit
      coupling (SOC) interactions. The self-Hermitian of this MTZF([Formula: see text])
      is similar to that of the Majorana fermions (MFs) ([Formula: see text]). We show
      that, to realize a single MTZF at each edge in superfluid with d-wave pairing in
      a Majorana type Kramers Doublet (MTKD) state, it is important to lift both the
      spin and the Dirac Cones degeneracies. These non-Abelian anyons obey the non
      Abelian statistics which may be useful to realize topological quantum
      computation. We suggest that the topological feature could be tested
      experimentally in superfluids of cold fermionic atoms with laser field induced
      spin orbit interactions. These studies give a new possible way to investigate the
      MTZFs in a two-dimensional (2D) system as compared to MFs in the one-dimensional
      (1D) nano-wire and 2D system, and enrich the theoretical research on finding non
      Abelian anyons in topological system.

PMID- 29051594
TI  - Reference genes validation in Phenacoccus solenopsis under various biotic and
      abiotic stress conditions.
AB  - Real-time PCR (RT-qPCR) expression analysis is a powerful analytical technique,
      but for normalization of data requires the use of stable reference genes.
      However, suitable reference genes are still not known in the case of Phenacoccus
      solenopsis under variable experimental treatments. The present study focused on
      the identification of stable housekeeping genes as a reference for analysis under
      different abiotic and biotic factors in P. solenopsis. We analyzed the relative
      expression of six commonly used candidate reference genes in different
      developmental stages, host-feeding assay, temperature treatments and field
      distribution conditions. Expression stabilities were analyzed by geNorm,
      NormFinder, and RefFinder. Under developmental and field distribution conditions,
      beta-Tubulin was found to be most stable reference genes followed by rpl32 and
      alpha-Tubulin. In the case host feeding treatment conditions, beta-Tubulin and
      alpha-tubulin identified to be the most stable reference genes, while in
      temperature stress, a combination of alpha-Tubulin and rpl32 found to be suitable
      for normalizing the RT-qPCR data. Further, the above-identified genes were
      validated using RT-qPCR based gene expression analysis of four objective genes
      namely, Myoinhibitory peptides (MIPs), Zinc_metalloprotease (Zn_Mp), fatty acid
      synthase (fas) and alpha-glucosidase. Identified reference genes will facilitate
      gene expression studies in future under different stress treatments in P.
      solenopsis.

PMID- 29051595
TI  - A virus carries a gene encoding juvenile hormone acid methyltransferase, a key
      regulatory enzyme in insect metamorphosis.
AB  - Microbial parasitism, infection, and symbiosis in animals often modulate host
      endocrine systems, resulting in alterations of phenotypic traits of the host that
      can have profound effects on the ecology and evolution of both the microorganisms
      and their hosts. Information about the mechanisms and genetic bases of such
      modulations by animal parasites is available from studies of steroid hormones.
      However, reports involving other hormones are scarce. We found that an insect
      virus, a betaentomopoxvirus, encodes a juvenile hormone acid methyltransferase
      that can synthesize an important insect hormone, the sesquiterpenoid juvenile
      hormone. Phylogenetic analysis suggested that this gene is of bacterial origin.
      Our study challenges the conventional view that functional enzymes in the late
      phase of the juvenile hormone biosynthesis pathway are almost exclusive to
      insects or arthropods, and shed light on juvenoid hormone synthesis beyond
      Eukaryota. This striking example demonstrates that even animal parasites having
      no metabolic pathways for molecules resembling host hormones can nevertheless
      influence the synthesis of such hormones, and provides a new context for studying
      animal parasite strategies in diverse systems such as host-parasite, host
      symbiont or host-vector-parasite.

PMID- 29051596
TI  - Quantifying Quantum-Mechanical Processes.
AB  - The act of describing how a physical process changes a system is the basis for
      understanding observed phenomena. For quantum-mechanical processes in particular,
      the affect of processes on quantum states profoundly advances our knowledge of
      the natural world, from understanding counter-intuitive concepts to the
      development of wholly quantum-mechanical technology. Here, we show that quantum
      mechanical processes can be quantified using a generic classical-process model
      through which any classical strategies of mimicry can be ruled out. We
      demonstrate the success of this formalism using fundamental processes postulated
      in quantum mechanics, the dynamics of open quantum systems, quantum-information
      processing, the fusion of entangled photon pairs, and the energy transfer in a
      photosynthetic pigment-protein complex. Since our framework does not depend on
      any specifics of the states being processed, it reveals a new class of
      correlations in the hierarchy between entanglement and Einstein-Podolsky-Rosen
      steering and paves the way for the elaboration of a generic method for
      quantifying physical processes.

PMID- 29051597
TI  - Controlling for Confounding Effects in Single Cell RNA Sequencing Studies Using
      both Control and Target Genes.
AB  - Single cell RNA sequencing (scRNAseq) technique is becoming increasingly popular
      for unbiased and high-resolutional transcriptome analysis of heterogeneous cell
      populations. Despite its many advantages, scRNAseq, like any other genomic
      sequencing technique, is susceptible to the influence of confounding effects.
      Controlling for confounding effects in scRNAseq data is a crucial step for
      accurate downstream analysis. Here, we present a novel statistical method, which
      we refer to as scPLS (single cell partial least squares), for robust and accurate
      inference of confounding effects. scPLS takes advantage of the fact that genes in
      a scRNAseq study often can be naturally classified into two sets: a control set
      of genes that are free of effects of the predictor variables and a target set of
      genes that are of primary interest. By modeling the two sets of genes jointly
      using the partial least squares regression, scPLS is capable of making full use
      of the data to improve the inference of confounding effects. With extensive
      simulations and comparisons with other methods, we demonstrate the effectiveness
      of scPLS. Finally, we apply scPLS to analyze two scRNAseq data sets to illustrate
      its benefits in removing technical confounding effects as well as for removing
      cell cycle effects.

PMID- 29051598
TI  - Multifunctional surface designed by nanocomposite coating of
      polytetrafluoroethylene and TiO2 photocatalyst: self-cleaning and
      superhydrophobicity.
AB  - Multifunctional surface, having both a superhydrophobic property and a
      photocatalytic self-cleaning property, was designed through a nanocomposite
      coating of polytetrafluoroethylene (PTFE) and TiO2 photocatalyst onto a flat
      quartz glass with a precise structural controlling by applying a radio frequency
      magnetron sputtering deposition technique. Systematic water contact angle
      measurements were carried out in relation to the controlling of the surface
      structure such as size, height and others. Surface wettability gradually changes
      from Wenzel state to Cassie-Baxter state by controlling of the surface structure,
      resulting in a well water repellent behavior. Under irradiation of UV light,
      nanocomposite coating with a desired surface structure and composition realized
      an adequate photocatalytic self-cleaning property for keeping a clean surface and
      inducing unique surface wettability changes.

PMID- 29051599
TI  - Using quartz sand to enhance the removal efficiency of M. aeruginosa by inorganic
      coagulant and achieve satisfactory settling efficiency.
AB  - In this study, low-cost and non-polluting quartz sand was respectively mixed with
      AlCl3, FeCl3 and PAFC to synergistically remove Microcystis aeruginosa. Results
      showed that quartz sand could markedly increase the algae removal efficiency and
      decrease the coagulant doses. The increase of removal efficiency with AlCl3 and
      FeCl3 was only due to the enhancement of floc density by the quartz sand.
      However, the removal efficiency with PAFC was increased not only by the enhanced
      floc density, but also by the enlarged floc size. Flocs from 50 mg/L sand
      addition were larger than that with other sand doses, which was on account of the
      appropriate enhancement of collision efficiency at this dose. After coagulation,
      the extracellular organic matter (EOM) and microcystins (MCs) in system with
      quartz sand was remarkably reduced. That's because quartz sand can enhance the
      coagulation so as to improve capping the EOM and MCs in flocs during coagulation
      process. Owing to 200 mg/L quartz sand could damage the cell's membrane during
      coagulation proces, algal cells in the system lysed two days earlier than with 50
      mg/L sand during flocs storage. In addition, cells with PAFC incurred relatively
      moderate cellular oxidative damage and could remain intact for longer time.

PMID- 29051600
TI  - Prediction of Treatment Response for Combined Chemo- and Radiation Therapy for
      Non-Small Cell Lung Cancer Patients Using a Bio-Mathematical Model.
AB  - The goal of this work was to develop a mathematical model to predict Kaplan-Meier
      survival curves for chemotherapy combined with radiation in Non-Small Cell Lung
      Cancer patients for use in clinical trial design. The Gompertz model was used to
      describe tumor growth, radiation effect was simulated by the linear-quadratic
      model with an alpha/beta-ratio of 10, and chemotherapy effect was based on the
      log-cell kill model. To account for repopulation during treatment, we considered
      two independent methods: 1) kickoff-repopulation using exponential growth with a
      decreased volume doubling time, or 2) Gompertz-repopulation using the gradually
      accelerating growth rate with tumor shrinkage. The input parameters were
      independently estimated by fitting to the SEER database for untreated tumors,
      RTOG-8808 for radiation only, and RTOG-9410 for sequential chemo-radiation.
      Applying the model, the benefit from concurrent chemo-radiation comparing to
      sequential for stage III patients was predicted to be a 6.6% and 6.2% improvement
      in overall survival for 3 and 5-years respectively, comparing well to the 5.3%
      and 4.5% observed in RTOG-9410. In summary, a mathematical model was developed to
      model tumor growth over extended periods of time, and can be used for the
      optimization of combined chemo-radiation scheduling and sequencing.

PMID- 29051602
TI  - Electron tunneling through double magnetic barriers in Weyl semimetals.
AB  - We theoretically investigate the transport in a magnetic/normal/magetic hybrid
      structure on the surface of a Weyl semimetal. We find a directional-dependent
      tunneling which is sensitive to the magnetic field configuration and the electric
      gate voltage. The momentum filtering behavior becomes more significant for two
      delta-function-shaped magnetic barriers. There are many Fabry-Perot resonances in
      the transmission determined by the distance between the two magnetic barriers.
      The combined effects of the magnetic field and the electrostatic potential can
      enhance the difference in the transmission between the parallel and antiparallel
      magnetization configurations, and consequently lead to a giant magnetoresistance.

PMID- 29051601
TI  - Altered behavioral and amygdala habituation in high-functioning adults with
      autism spectrum disorder: an fMRI study.
AB  - Habituation to repeatedly presented stimuli is an important adaptive property of
      the nervous system. Autism spectrum disorder (ASD) has been associated with
      reduced neural habituation, for example in the amygdala, which may be related to
      social impairments. The main focus of this study was to investigate habituation
      effects on the level of behavioral responses as well as amygdala responses in
      adults with ASD during a working memory task flanked by task-irrelevant face
      stimuli. Twenty-two patients with high-functioning autism and 24 healthy controls
      (HC) were included in this functional magnetic resonance imaging (fMRI) study. We
      employed an established habituation index to investigate habituation effects.
      Suggestive of altered habituation, the habituation index showed a decrement of
      reaction time over the course of the experiment in the HC but not in the ASD
      group. Similarly, an expected pattern of habituation was evident in amygdala
      activation in HC but absent in ASD participants. These results provide evidence
      that habituation may be altered not only on a neural, but also on a behavioral
      level in ASD. While more research is needed to develop a better understanding of
      the underlying mechanisms, the current findings support the possibility that
      deficient habituation may be a biomarker of ASD.

PMID- 29051603
TI  - Quantitative assessment of the blood-brain barrier opening caused by
      Streptococcus agalactiae hyaluronidase in a BALB/c mouse model.
AB  - Streptococcus agalactiae is a pathogen causing meningitis in animals and humans.
      However, little is known about the entry of S. agalactiae into brain tissue. In
      this study, we developed a BALB/c mouse model based on the intravenous injection
      of beta-galactosidase-positive Escherichia coli M5 as an indicator of blood-brain
      barrier (BBB) opening. Under physiological conditions, the BBB is impermeable to
      E. coli M5. In pathological conditions caused by S. agalactiae, E. coli M5 is
      capable of penetrating the brain through a disrupted BBB. The level of BBB
      opening can be assessed by quantitative measurement of E. coli M5 loads per gram
      of brain tissue. Further, we used the model to evaluate the role of S. agalactiae
      hyaluronidase in BBB opening. The inactivation of hylB gene encoding a
      hyaluronidase, HylB, resulted in significantly decreased E. coli M5 colonization,
      and the intravenous injection of purified HylB protein induced BBB opening in a
      dose-dependent manner. This finding verified the direct role of HylB in BBB
      invasion and traversal, and further demonstrated the practicability of the in
      vivo mouse model established in this study. This model will help to understand
      the S. agalactiae-host interactions that are involved in this bacterial traversal
      of the BBB and to develop efficacious strategies to prevent central nervous
      system infections.

PMID- 29051604
TI  - Silicon Nitride Deposition for Flexible Organic Electronic Devices by VHF (162
      MHz)-PECVD Using a Multi-Tile Push-Pull Plasma Source.
AB  - Depositing a barrier film for moisture protection without damage at a low
      temperature is one of the most important steps for organic-based electronic
      devices. In this study, the authors investigated depositing thin, high-quality
      SiNx film on organic-based electronic devices, specifically, very high-frequency
      (162 MHz) plasma-enhanced chemical vapor deposition (VHF-PECVD) using a multi
      tile push-pull plasma source with a gas mixture of NH3/SiH4 at a low temperature
      of 80  degrees C. The thin deposited SiNx film exhibited excellent properties in
      the stoichiometry, chemical bonding, stress, and step coverage. Thin film quality
      and plasma damage were investigated by the water vapor transmission rate (WVTR)
      and by electrical characteristics of organic light-emitting diode (OLED) devices
      deposited with SiNx, respectively. The thin deposited SiNx film exhibited a low
      WVTR of 4.39 * 10-4 g (m2 . day)-1 for a single thin (430 nm thick) film SiNx and
      the electrical characteristics of OLED devices before and after the thin SiNx
      film deposition on the devices did not change, which indicated no electrical
      damage during the deposition of SiNx on the OLED device.

PMID- 29051605
TI  - Milling overrides cultivar, leavening agent and baking mode on chemical and
      rheological traits and sensory perception of durum wheat breads.
AB  - Smell and aroma are important determinants of consumer acceptance, so gaining
      deeper insight into bread smell and aroma perception is a research goal. Sixteen
      combinations of four variables were investigated, to evaluate the contributions
      of bread chemical and rheological properties and volatile organic compounds
      (VOCs) towards sensory acceptability of breads: genotypes (landrace vs. modern);
      types of flour (wholemeal vs. semolina); leavening agents (brewing yeast vs.
      sourdough starter); and baking modes (gas-fired vs. wood-fired). Milling had the
      greatest impact over the other treatments for the rheological and chemical
      properties, including for VOCs, with great impact on the sensory traits of the
      flours and breads. The processing phases had great impact on smell and aroma, as
      defined through formation of alcohols, aldehydes, terpenes, and other compounds
      (e.g., ethylbenzene, 2-pentylfuran, methoxyphenyl oxime). Leavening agent had
      great impact on sensory perception, although breads from the sourdough starter
      were perceived as with lower taste and colour than the brewing yeast. Baking mode
      had no relevant role on sensory perception. These data strongly undermine the
      belief of a 'better product' that is frequently attributed to old genotypes
      versus modern cultivars, and indicate that the milling and the bread-making
      processes determine the quality of the end product.

PMID- 29051607
TI  - Isotopic compositions of 236U, 239Pu, and 240Pu in soil contaminated by the
      Fukushima Daiichi Nuclear Power Plant accident.
AB  - Six years after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, data
      for 236U and 236U/238U have remained limited to a few heavily contaminated
      samples. In the present study, activities of 236U, 239Pu, and 240Pu, along with
      other U isotopes in 46 soil samples both heavily and lightly contaminated by this
      accident were measured by inductively coupled plasma-mass spectrometry (ICP-MS)
      and triple-quadrupole ICP-MS. The 236U activities and 236U/238U atom ratios in
      these soil samples were in the range of (0.469-24.4) * 10-5 Bq kg-1 and ((0.099
      1.35) * 10-7), respectively. Higher 240Pu/239Pu atom ratios (0.245-0.312) and
      238Pu/239+240Pu activity ratios (0.859-1.62) indicated Pu contamination
      originated from this accident and global fallout in some samples. For those soil
      samples along with black substances collected along roads in Fukushima
      Prefecture, high linear correlations were presented between 236U activities and
      239+240Pu activities (Pearson's r = 0.755, p < 0.01), and between 236U activities
      and 238Pu activities (Pearson's r = 0.844, p < 0.01). The analysis of these soil
      samples confirmed the release of 236U, although in trace amounts, during the
      FDNPP accident.

PMID- 29051606
TI  - Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast
      cancer cells.
AB  - TFPI-2 has recently been recognized as a tumor suppressor, which not only plays a
      fundamental role in modulation of ECM integrity, but also involves the regulation
      of many oncogenes. In this study, we investigated the potential mechanism of TFPI
      2 in the suppression of breast cancer growth and invasion. We showed that, with
      either over-expression of TFPI-2 or after treatment with exogenous rTFPI-2,
      breast cancer cells exhibited reduced proliferation and invasion. We demonstrated
      that in addition to being secreted, TFPI-2 was also distributed throughout the
      cytoplasm and nucleus. Nuclear localization of TFPI-2 contributed to inhibition
      of MMP-2 mRNA expression, which could be reversed after the nuclear localization
      signal was deleted. In the nucleus, interaction of TFPI-2 with Ap-2alpha
      attenuated the binding of AP-2alpha to the MMP-2 promoter, therefore reducing the
      transcriptional activity of the gene. Our results suggest that one of the
      mechanisms by which TFPI-2 inhibits breast cancer cell invasion could be via the
      regulation of MMP-2 gene transcription.

PMID- 29051608
TI  - Transcription factors and stress response gene alterations in human keratinocytes
      following Solar Simulated Ultra Violet Radiation.
AB  - Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging
      and carcinogenesis. However, genes and pathways altered by solar-simulated UVR
      (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report
      global changes in gene expression as well as associated pathways and upstream
      transcription factors in human keratinocytes exposed to ssUVR. Human HaCaT
      keratinocytes were exposed to either a single dose or 5 repetitive doses of
      ssUVR. Comprehensive analyses of gene expression profiles as well as functional
      annotation were performed at 24 hours post irradiation. Our results revealed that
      ssUVR modulated genes with diverse cellular functions changed in a dose-dependent
      manner. Gene expression in cells exposed to a single dose of ssUVR differed
      significantly from those that underwent repetitive exposures. While single ssUVR
      caused a significant inhibition in genes involved in cell cycle progression,
      especially G2/M checkpoint and mitotic regulation, repetitive ssUVR led to
      extensive changes in genes related to cell signaling and metabolism. We have also
      identified a panel of ssUVR target genes that exhibited persistent changes in
      gene expression even at 1 week after irradiation. These results revealed a
      complex network of transcriptional regulators and pathways that orchestrate the
      cellular response to ssUVR.

PMID- 29051609
TI  - Liquid-infused nitric oxide-releasing (LINORel) silicone for decreased fouling,
      thrombosis, and infection of medical devices.
AB  - Recent reports on liquid-infused materials have shown promise in creating ultra
      low fouling surfaces, but are limited in their ability to prevent bacterial
      proliferation and prevent platelet activation in blood-contacting applications.
      In this work, a liquid-infused nitric oxide-releasing (LINORel) material is
      created by incorporating the nitric oxide (NO) donor S-nitroso
      acetylpenicillamine (SNAP) and silicone oil in commercial medical grade silicone
      rubber tubing through a solvent swelling process. This combination provides
      several key advantages over previous NO-releasing materials, including decreased
      leaching of NO donor, controlled release of NO, and maintenance of ultra-low
      fouling property of liquid-infused materials. The LINORel tubing reduces protein
      adhesion as observed using fluorescence imaging, and platelet adhesion (81.7 +/-
      2.5%) in vitro over a 2 h period. The LINORel combination greatly reduces
      bacterial adhesion and biofilm formation of two most common pathogens responsible
      for hospital acquired infections: gram-positive Staphylococcus aureus and gram
      negative Pseudomonas aeruginosa (99.3 +/- 1.9% and 88.5 +/- 3.3% respectively)
      over a 7-day period in a CDC bioreactor environment. Overall, the LINORel
      approach provides a synergistic combination of active and passive non-fouling
      approaches to increase biocompatibility and reduce infection associated with
      medical devices.

PMID- 29051610
TI  - Changes in land use alter soil quality and aggregate stability in the highlands
      of northern Ethiopia.
AB  - Land use change alters biodiversity and soil quality and thus affects ecosystem
      functions. This study investigated the effects of changes in land use on major
      soil quality indicators. Soil samples were taken from a depth of 0-10 cm (top
      soil) under four major land uses (cropland, grassland, area exclosure, eucalyptus
      plantation) with similar land use change histories for analysis, and soil from a
      nearby natural forest was used as a reference. Land use change from natural
      forest to cropland and grassland significantly decreased major soil quality
      indicators such as soil organic C (SOC), total soil N (TSN), molybdate-reactive
      bicarbonate-extractable P, and arbuscular mycorrhizal fungi (AMF) spore density,
      but compared to the cropland, change to area exclosure and eucalyptus plantation
      significantly improved SOC, TSN and soil aggregate stability (SAS). In addition,
      we assessed the correlation among indicators and found that SOC, TSN and SAS
      significantly correlate with many other soil quality indicators. The study
      highlights that the conversion of natural forest to cropland results in decline
      of soil quality and aggregate stability. However, compared to cropland,
      application of area exclosure and afforestation on degraded lands restores soil
      quality and aggregate stability.

PMID- 29051611
TI  - Porous nitrogen-enriched carbonaceous material from marine waste: chitosan
      derived carbon nitride catalyst for aerial oxidation of 5-hydroxymethylfurfural
      (HMF) to 2,5-furandicarboxylic acid.
AB  - Chitosan-derived, porous nitrogen-enriched carbonaceous carbon nitride catalyst
      (PCNx) has been synthesized from marine waste and its use demonstrated in a metal
      free heterogeneous selective oxidation of 5-hydroxymethyl-furfural (HMF) to 2,5
      furandicarboxylic acid (FDCA) using aerial oxygen under mild reaction conditions.

PMID- 29051612
TI  - The Orbiting Carbon Observatory (OCO-2) tracks 2-3 peta-gram increase in carbon
      release to the atmosphere during the 2014-2016 El Nino.
AB  - The powerful El Nino event of 2015-2016 - the third most intense since the 1950s 
      has exerted a large impact on the Earth's natural climate system. The column
      averaged CO2 dry-air mole fraction (XCO2) observations from satellites and ground
      based networks are analyzed together with in situ observations for the period of
      September 2014 to October 2016. From the differences between satellite (OCO-2)
      observations and simulations using an atmospheric chemistry-transport model, we
      estimate that, relative to the mean annual fluxes for 2014, the most recent El
      Nino has contributed to an excess CO2 emission from the Earth's surface (land +
      ocean) to the atmosphere in the range of 2.4 +/- 0.2 PgC (1 Pg = 1015 g) over the
      period of July 2015 to June 2016. The excess CO2 flux is resulted primarily from
      reduction in vegetation uptake due to drought, and to a lesser degree from
      increased biomass burning. It is about the half of the CO2 flux anomaly (range:
      4.4-6.7 PgC) estimated for the 1997/1998 El Nino. The annual total sink is
      estimated to be 3.9 +/- 0.2 PgC for the assumed fossil fuel emission of 10.1 PgC.
      The major uncertainty in attribution arise from error in anthropogenic emission
      trends, satellite data and atmospheric transport.

PMID- 29051613
TI  - Electrochemical Magnetization Switching and Energy Storage in Manganese Oxide
      filled Carbon Nanotubes.
AB  - The ferrimagnetic and high-capacity electrode material Mn3O4 is encapsulated
      inside multi-walled carbon nanotubes (CNT). We show that the rigid hollow
      cavities of the CNT enforce size-controlled nanoparticles which are
      electrochemically active inside the CNT. The ferrimagnetic Mn3O4 filling is
      switched by electrochemical conversion reaction to antiferromagnetic MnO. The
      conversion reaction is further exploited for electrochemical energy storage. Our
      studies confirm that the theoretical reversible capacity of the Mn3O4 filling is
      fully accessible. Upon reversible cycling, the Mn3O4@CNT nanocomposite reaches a
      maximum discharge capacity of 461 mA h g-1 at 100 mA g-1 with a capacity
      retention of 90% after 50 cycles. We attribute the good cycling stability to the
      hybrid nature of the nanocomposite: (1) Carbon encasements ensure electrical
      contact to the active material by forming a stable conductive network which is
      unaffected by potential cracks of the encapsulate. (2) The CNT shells resist
      strong volume changes of the encapsulate in response to electrochemical cycling,
      which in conventional (i.e., non-nanocomposite) Mn3O4 hinders the application in
      energy storage devices. Our results demonstrate that Mn3O4 nanostructures can be
      successfully grown inside CNT and the resulting nanocomposite can be reversibly
      converted and exploited for lithium-ion batteries.

PMID- 29051614
TI  - Genome-wide identification of microRNAs responsive to Ectropis oblique feeding in
      tea plant (Camellia sinensis L.).
AB  - The tea plant (Camellia sinensis L.) is vulnerable to the geometrid Ectropis
      oblique; although microRNAs (miRNAs) are important for plant growth, development
      and stress response, the function of miRNAs in the response of C. sinensis to
      stress from E. oblique is unclear. To identify E. oblique stress-responsive
      miRNAs and their target genes in tea plant, three small RNA libraries were
      constructed from leaves subjected to mechanical wounding (MW), geometrid attack
      (GA) and from healthy control (CK) leaves. Using high-throughput sequencing, 130
      known miRNAs and 512 novel miRNAs were identified; of these, differential
      expression under GA stress was observed for 36 known and 139 novel miRNAs.
      Furthermore, 169 GA-responsive and 173 MW-responsive miRNAs were detected by
      miRNA microarray. The expression patterns of six GA-responsive miRNAs were
      validated by qRT-PCR. Several target genes for these miRNAs encode various
      transcription factors, including ethylene-responsive transcription factors and
      squamosa promoter-binding-like proteins, which suggests that these miRNAs may
      regulate stress-responsive transcriptional processes in tea plant. The present
      findings provide novel insights into miRNA-mediated regulatory mechanisms
      underlying the response to GA stress, and also offer valuable information for
      development of pest resistance using RNA interference-based strategies in tea
      plants.

PMID- 29051615
TI  - Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal
      mice.
AB  - Identification of the causal effects of specific proteins on recurrent and
      partially reversible hearing loss has been difficult because of the lack of an
      animal model that provides reversible gene knockdown. We have developed the
      transgenic mouse line Actin-tTS::Nkcc1 tetO/tetO for manipulatable expression of
      the cochlear K+ circulation protein, NKCC1. Nkcc1 transcription was blocked by
      the binding of a tetracycline-dependent transcriptional silencer to the
      tetracycline operator sequences inserted upstream of the Nkcc1 translation
      initiation site. Administration of the tetracycline derivative doxycycline
      reversibly regulated Nkcc1 knockdown. Progeny from pregnant/lactating mothers fed
      doxycycline-free chow from embryonic day 0 showed strong suppression of Nkcc1
      expression (~90% downregulation) and Nkcc1 null phenotypes at postnatal day 35
      (P35). P35 transgenic mice from mothers fed doxycycline-free chow starting at P0
      (delivery) showed weaker suppression of Nkcc1 expression (~70% downregulation)
      and less hearing loss with mild cochlear structural changes. Treatment of these
      mice at P35 with doxycycline for 2 weeks reactivated Nkcc1 transcription to
      control levels and improved hearing level at high frequency; i.e., these
      doxycycline-treated mice exhibited partially reversible hearing loss. Thus,
      development of the Actin-tTS::Nkcc1 tetO/tetO transgenic mouse line provides a
      mouse model for the study of variable hearing loss through reversible knockdown
      of Nkcc1.

PMID- 29051616
TI  - Effects of inoculants Lactobacillus brevis and Lactobacillus parafarraginis on
      the fermentation characteristics and microbial communities of corn stover silage.
AB  - To improve silage quality of crop forages, bacterial inoculants are often
      employed. In this study, Lactobacillus brevis SDMCC050297 and Lactobacillus
      parafarraginis SDMCC050300 were used as inoculants to corn stover in lab silos
      for ensiling. At the initial stage of ensiling, the pH value of the inoculated
      silages reduced more drastically, and the inoculated silages had higher lactic
      acid and acetic acid contents. After 20 days of ensiling, a reduction in lactic
      acid content coupled with an increase in acetic acid and 1,2-propanediol contents
      was observed in inoculated silages. Furthermore, both the amount of lactic acid
      bacteria and the abundance of order Lactobacillales in inoculated silages were
      higher than those of controls in the whole process. Meanwhile, Lb. brevis
      predominated before day 20 and then the dominance was shifted to Lb.
      parafarraginis until the late stage of ensiling. In contrast, the epiphytic
      Lactococcus lactic and Lb. plantarum played major roles at the beginning of
      naturally fermented silages and then Lb. plantarum and Lb. brevis were the most
      abundant at the later stage. In conclusion, these two selected strains had
      capability of improving the silage quality and providing the reproducible
      ensiling process, thus having the potential as silage inoculants.

PMID- 29051617
TI  - Author Correction: Mammal diversity influences the carbon cycle through trophic
      interactions in the Amazon.
AB  - In the version of this Article originally published, the surname of Ted K. Raab
      was misspelt. This error has now been corrected in all versions of the Article.

PMID- 29051618
TI  - Development and validation of a risk prediction model for work disability:
      multicohort study.
AB  - Work disability affects quality of life, earnings, and opportunities to
      contribute to society. Work characteristics, lifestyle and sociodemographic
      factors have been associated with the risk of work disability, but few
      multifactorial algorithms exist to identify individuals at risk of future work
      disability. We developed and validated a parsimonious multifactorial score for
      the prediction of work disability using individual-level data from 65,775 public
      sector employees (development cohort) and 13,527 employed adults from a general
      population sample (validation cohort), both linked to records of work disability.
      Candidate predictors for work disability included sociodemographic (3 items),
      health status and lifestyle (38 items), and work-related (43 items) variables. A
      parsimonious model, explaining > 99% of the variance of the full model, comprised
      8 predictors: age, self-rated health, number of sickness absences in previous
      year, socioeconomic position, chronic illnesses, sleep problems, body mass index,
      and smoking. Discriminative ability of a score including these predictors was
      high: C-index 0.84 in the development and 0.83 in the validation cohort. The
      corresponding C-indices for a score constructed from work-related predictors
      (age, sex, socioeconomic position, job strain) were 0.79 and 0.78, respectively.
      It is possible to identify reliably individuals at high risk of work disability
      by using a rapidly-administered prediction score.

PMID- 29051619
TI  - Person identification from aerial footage by a remote-controlled drone.
AB  - Remote-controlled aerial drones (or unmanned aerial vehicles; UAVs) are employed
      for surveillance by the military and police, which suggests that drone-captured
      footage might provide sufficient information for person identification. This
      study demonstrates that person identification from drone-captured images is poor
      when targets are unfamiliar (Experiment 1), when targets are familiar and the
      number of possible identities is restricted by context (Experiment 2), and when
      moving footage is employed (Experiment 3). Person information such as sex, race
      and age is also difficult to access from drone-captured footage (Experiment 4).
      These findings suggest that such footage provides a particularly poor medium for
      person identification. This is likely to reflect the sub-optimal quality of such
      footage, which is subject to factors such as the height and velocity at which
      drones fly, viewing distance, unfavourable vantage points, and ambient
      conditions.

PMID- 29051620
TI  - Antimicrobial peptide-loaded gold nanoparticle-DNA aptamer conjugates as highly
      effective antibacterial therapeutics against Vibrio vulnificus.
AB  - Vibrio vulnificus causes fatal infections in humans, and antibiotics are commonly
      used in treatment regimens against V. vulnificus infection. However, the
      therapeutic effects of antibiotics are limited by multidrug resistance. In this
      study, we demonstrated that an antimicrobial peptide (AMP), HPA3PHis, loaded onto
      a gold nanoparticle-DNA aptamer (AuNP-Apt) conjugate (AuNP-Apt-HPA3PHis) is an
      effective therapeutic tool against V. vulnificus infection in vivo in mice.
      HPA3PHis induced bacterial cell death through the disruption of membrane
      integrity of V. vulnificus. The introduction of AuNP-Apt-HPA3PHis into V.
      vulnificus-infected HeLa cells dramatically reduced intracellular V. vulnificus
      by 90%, leading to an increase in the viability of the infected cells. Moreover,
      when V. vulnificus-infected mice were intravenously injected with AuNP-Apt
      HPA3PHis, a complete inhibition of V. vulnificus colonization was observed in the
      mouse organs, leading to a 100% survival rate among the treated mice, whereas all
      the control mice died within 40 hours of being infected. Therefore, this study
      demonstrated the potential of an AMP delivered by AuNP-Apt as an effective and
      rapid treatment option against infection caused by a major pathogen in humans and
      aquatic animals.

PMID- 29051621
TI  - Vector-independent transmembrane transport of oligodeoxyribonucleotides involves
      p38 mitogen activated protein kinase phosphorylation.
AB  - The main roles of equilibrative nucleoside transporters (ENTs) and concentrative
      nucleoside transporters (CNTs) are to transfer single nucleosides and analogues
      for the nucleic acid salvage pathway. Oligodeoxyribonucleotides (ODNs) can be
      transported into the cytoplasm or nucleus of cells under certain conditions.
      Among ODNs composed of a single type of nucleotide, the transport efficiency
      differs with the length and nucleotide composition of the ODNs and varies in
      different types of leukaemia cells; among the 5 tested random sequence ODNs and 3
      aptamers with varying sequences, the data showed that some sequences were
      associated with significantly higher transport efficiency than others. The
      transport of ODNs was sodium, energy, and pH-independent, membrane protein
      dependent, substrate nonspecific for ODNs and 4-nitrobenzylthioinosine (NBMPR)
      insensitive, but it showed a low sensitivity to dipyridamole (IC50 = 35.44
      umol/L), distinguishing it from ENT1-4 and CNTs. The delivery efficiency of ODNs
      was superior to that of Lipofection and Nucleofection, demonstrating its
      potential applications in research or therapeutics. Moreover, this process was
      associated with p38 mitogen activated protein kinase (p38MAPK) instead of c-Jun N
      terminal kinase (JNK) signalling pathways. We have denoted ODN transmembrane
      transport as equilibrative nucleic acid transport (ENAT). Overall, these findings
      indicate a new approach and mechanism for transmembrane transport of ODNs.

PMID- 29051623
TI  - Vasculitis syndromes: Rituximab for adult-onset IgA vasculitis.

PMID- 29051624
TI  - Autoinflammation: Stem cell transplantation for DADA2.

PMID- 29051625
TI  - Paediatric rheumatology: DNA methylation in oligoarticular JIA.

PMID- 29051622
TI  - Genome-Guided Phylo-Transcriptomic Methods and the Nuclear Phylogentic Tree of
      the Paniceae Grasses.
AB  - The past few years have witnessed a paradigm shift in molecular systematics from
      phylogenetic methods (using one or a few genes) to those that can be described as
      phylogenomics (phylogenetic inference with entire genomes). One approach that has
      recently emerged is phylo-transcriptomics (transcriptome-based phylogenetic
      inference). As in any phylogenetics experiment, accurate orthology inference is
      critical to phylo-transcriptomics. To date, most analyses have inferred orthology
      based either on pure sequence similarity or using gene-tree approaches. The use
      of conserved genome synteny in orthology detection has been relatively under
      employed in phylogenetics, mainly due to the cost of sequencing genomes. While
      current trends focus on the quantity of genes included in an analysis, the use of
      synteny is likely to improve the quality of ortholog inference. In this study, we
      combine de novo transcriptome data and sequenced genomes from an economically
      important group of grass species, the tribe Paniceae, to make phylogenomic
      inferences. This method, which we call "genome-guided phylo-transcriptomics", is
      compared to other recently published orthology inference pipelines, and
      benchmarked using a set of sequenced genomes from across the grasses. These
      comparisons provide a framework for future researchers to evaluate the costs and
      benefits of adding sequenced genomes to transcriptome data sets.

PMID- 29051626
TI  - Crystal arthritis: Febuxostat reduces synovitis in early gout.

PMID- 29051627
TI  - Rainbow-trapping absorbers: Broadband, perfect and asymmetric sound absorption by
      subwavelength panels for transmission problems.
AB  - Perfect, broadband and asymmetric sound absorption is theoretically, numerically
      and experimentally reported by using subwavelength thickness panels in a
      transmission problem. The panels are composed of a periodic array of varying
      crosssection waveguides, each of them being loaded by Helmholtz resonators (HRs)
      with graded dimensions. The low cut-off frequency of the absorption band is fixed
      by the resonance frequency of the deepest HR, that reduces drastically the
      transmission. The preceding HR is designed with a slightly higher resonance
      frequency with a geometry that allows the impedance matching to the surrounding
      medium. Therefore, reflection vanishes and the structure is critically coupled.
      This results in perfect sound absorption at a single frequency. We report perfect
      absorption at 300 Hz for a structure whose thickness is 40 times smaller than the
      wavelength. Moreover, this process is repeated by adding HRs to the waveguide,
      each of them with a higher resonance frequency than the preceding one. Using this
      frequency cascade effect, we report quasi-perfect sound absorption over almost
      two frequency octaves ranging from 300 to 1000 Hz for a panel composed of 9
      resonators with a total thickness of 11 cm, i.e., 10 times smaller than the
      wavelength at 300 Hz.

PMID- 29051628
TI  - Deadly acute Decompression Sickness in Risso's dolphins.
AB  - Diving air-breathing vertebrates have long been considered protected against
      decompression sickness (DCS) through anatomical, physiological, and behavioural
      adaptations. However, an acute systemic gas and fat embolic syndrome similar to
      DCS in human divers was described in beaked whales that stranded in temporal and
      spatial association with military exercises involving high-powered sonar. More
      recently, DCS has been diagnosed in bycaught sea turtles. Both cases were linked
      to human activities. Two Risso's dolphin (Grampus griseus) out of 493 necropsied
      cetaceans stranded in the Canary Islands in a 16-year period (2000-2015), had a
      severe acute decompression sickness supported by pathological findings and gas
      analysis. Deadly systemic, inflammatory, infectious, or neoplastic diseases, ship
      collision, military sonar, fisheries interaction or other type of lethal inducing
      associated trauma were ruled out. Struggling with a squid during hunting is
      discussed as the most likely cause of DCS.

PMID- 29051629
TI  - [Boerhaave's syndrome secondary to gastric volvulus].
AB  - Boerhaave's syndrome is a spontaneous rupture of the oesophagus, caused by an
      increase of intraluminal pressure that is produced in the context of negative
      intrathoracic pressure. It has a high index of morbimortality (14-40%), which is
      why it requires early diagnosis and treatment. When a patient presents vomiting,
      the differential diagnosis should include epigastric pain. Para-esophageal hiatal
      hernias can be complicated by gastric volvulus. In its turn, this can produce
      both oesophageal and gastric necrosis requiring early surgical treatment. We
      describe the case of an 83-year-old patient who presented gastric volvulus with
      complications from a hiatal hernia with associated vomiting, which triggered
      Boerhaave's syndrome. This is the second case published in the literature. Key
      words. Boerhaave's syndrome. Gastric volvulus. Surgical treatment.

PMID- 29051630
TI  - Adolescent Misconduct Behaviors: A Cross-Cultural Perspective of Adolescents and
      Their Parents.
AB  - The primary goal of the current study was to examine cultural differences in
      Chinese and U.S. adolescents' and parents' perceptions and evaluations of
      adolescent misconduct behaviors. A total of 395 U.S. and Chinese adolescents
      (ages 11-19 years) and 255 parents participated in this study. Each participant
      generated adolescent misconduct behaviors and rated each misconduct behavior as
      to the degree of wrongness. The misconduct behaviors were coded into 10
      categories across three themes (moral offenses, drugs, and conventions). Results
      revealed significant cultural differences in a number of adolescent misconduct
      behaviors. For example, the United States generated more misconduct behaviors in
      weapon offenses and drug use than did China. These cultural differences were
      further complicated by an interaction between culture and generation. Chinese
      adolescents were more likely than U.S. adolescents to use categories of school,
      home, and social conventional violations, and considered these adolescent
      misconduct behaviors to be more wrong. However, it was the U.S. parents who
      considered adolescent misconduct behaviors in these categories to be more wrong
      than did Chinese parents.

PMID- 29051631
TI  - Acoustic streaming: an arbitrary Lagrangian-Eulerian perspective.
AB  - We analyse acoustic streaming flows using an arbitrary Lagrangian Eulerian (ALE)
      perspective. The formulation stems from an explicit separation of time scales
      resulting in two subproblems: a first-order problem, formulated in terms of the
      fluid displacement at the fast scale, and a second-order problem, formulated in
      terms of the Lagrangian flow velocity at the slow time scale. Following a
      rigorous time-averaging procedure, the second-order problem is shown to be
      intrinsically steady, and with exact boundary conditions at the oscillating
      walls. Also, as the second-order problem is solved directly for the Lagrangian
      velocity, the formulation does not need to employ the notion of Stokes drift, or
      any associated post-processing, thus facilitating a direct comparison with
      experiments. Because the first-order problem is formulated in terms of the
      displacement field, our formulation is directly applicable to more complex fluid
      structure interaction problems in microacoustofluidic devices. After the
      formulation's exposition, we present numerical results that illustrate the
      advantages of the formulation with respect to current approaches.

PMID- 29051632
TI  - Preservation of orange juice using propolis.
AB  - Orange juice is one of the most popular and the most consumed fruit juices all
      over the world, especially in Europe and the chemical food preservatives, such as
      sodium benzoate, potassium sorbate and their mixtures, have long been used in
      orange juice sold on the market. Excessive consumption of these preservatives may
      be hazardous to human health. Propolis, composed of resins collected from plant
      buds and exudates and mixed with salivary gland secretions and beeswax by honey
      bee workers, has been used as a human medicine and natural food preservative. We
      hypothesis that propolis, without alcohol, can serve as an alternative and non
      synthetic preservative of orange juice. In this study, the preservative effect of
      propolis emulsion on orange juice was determined up to 35 days. Propolis emulsion
      (0.02 g/mL propolis, 12 mL), emulsion control (12 mL containing Tween-80,
      hydrophilic phospholipid and polyethylene glycol 400), sodium benzoate (0.4 g)
      and potassium sorbate (0.4 g) was each added to 388, 388, 400 and 400 mL orange
      juice respectively. Propolis emulsion showed significant inhibition of bacteria
      growth and l-ascorbic acid degradation. Orange juice pH value, titratable
      acidity, total phenolic content, color and antioxidant capacity were effectively
      maintained by propolis emulsion. A control solution with all the same emulsifying
      agents without propolis did not show these properties. It was concluded that
      propolis can be used as a natural additive agent in orange juice or other fruit
      juices as an alternative to chemical preservatives.

PMID- 29051633
TI  - Rapid test for the determination of total phenolic content in brewed-filtered
      coffee using colorimetric paper.
AB  - This work was aimed to develop a chemical sensor for the determination of total
      polyphenol content (TPC) of coffee samples. The polyphenol sensor was based on co
      immobilization of NaIO4 and MBTH in paper as a test strip. The sensor showed
      sensitive response to chlorogenic acid by forming pink color adduct which can be
      scanned and quantified by Imagej program. The sensor had response time of 14 min
      and a linear range between 0.07 and 0.71 mM of chlorogenic acid with a detection
      limit at 0.002 mM toward chlorogenic acid. The reproducibility of the sensor was
      good (RSD = 0.44%) with a life time within 27 days when stored at 4  degrees C.
      TPC of coffee samples were determined by the sensor, and the results were in
      agreement with the Folin-Ciocalteu method suggesting its practical use as a tool
      for TPC determination in coffee samples.

PMID- 29051634
TI  - Low sat-structured fats enriched in alpha-linolenic acid: physicochemical
      properties and crystallization characteristics.
AB  - This work sought to obtain and evaluate zero trans-fat reduced in saturated fatty
      acids, with higher content of unsaturated fatty acids. Palm oil (PO) was used as
      the reference of zero trans lipid base. Different amounts of linseed oil (LO)
      were added to PO, obtaining the following blends: 100:0; 80:20; 60:40; 40:60;
      20:80 and 0:100 of PO:LO (w/w%), respectively. These blends were added to fully
      hydrogenated soybean oil (FHSO) as the crystallization modifying agent, and to
      sorbitan monostearate (SMS) as the structuring element, both at a proportion of
      3% to build the structured fractions. The control and the structured blends were
      evaluated for fatty acid composition, solid fat content, consistency,
      crystallization kinetics, thermal behavior, microstructure and polymorphism. With
      the addition of LO to the PO, an increase of up to 80% was observed in the
      content of alpha-linolenic acid and a reduction of saturated fatty acids to 47%
      in the blends. FHSO and SMS offered thermal resistance to the blends, with
      relevant changes in the crystallization kinetics and microstructure, affecting
      macroscopic characteristics with the increase in consistence. It was possible to
      obtain a lipid formulation with features of plasticity and enhanced nutritional
      quality, compatible with several food applications.

PMID- 29051635
TI  - A comparison of the effects of heat moisture treatment (HMT) on rheological
      properties and amylopectin structure in sago (Metroxylon sago) and arenga (Arenga
      pinnata) starches.
AB  - The objective of this study was to study and compare the impact of HMT on
      rheology and textural properties observed between sago and arenga starces, and
      then related to structural change of amylopectin. The HMT were conducted using
      the autoclaving method at 20% moisture content and heated to 120 C for 60 min for
      sago and 90 min for arenga starch as optimum condition. The HMT shifted
      gelatinization temperature higher and reduced the enthalpy of both starches. The
      HMT sago starch paste exhibited an exceptionally strong shear thinning behavior
      as shown by a rapid decrease of viscosity and an increase of shear rate. The HMT
      clearly made the texture of starch gels more fragile compared to their native
      form and reduced their breaking point to a lower strain. The HMT effect on the
      rheological properties and texture of the sago starch was greater than the
      changes observed with the arenga starch. Major changes in rheological properties
      after HMT was not followed by changes in amylopectin structure. The HMT process
      did not significantly affect the amylopectin chain-length distribution in Arenga
      starch. In the sago starch, HMT affect to long chain amylopectin with DP >= 37.
      The HMT effect on rheology and textural properties was higher in sago starch than
      arenga starch. This study demonstrated that long chain amylopectin with DP >= 37
      plays an important role in contributing to the rheological change caused by the
      HMT.

PMID- 29051636
TI  - Effects of different carrier materials on physicochemical properties of
      microencapsulated grape skin extract.
AB  - The goal of this study was to investigate the characteristics of grape skin
      extract (GSE) spray dried with different carriers: maltodextrin (MD), gum Arabic
      (GA) and skim milk powder (SMP). The grape skin extract was obtained from winery
      by-product of red grape variety Prokupac (Vitis vinifera L.). The morphology of
      the powders, their thermal, chemical and physical properties (water activity,
      bulk and tapped densities, solubility), as well as release studies in different
      pH conditions were analyzed. Total anthocyanin content and total phenolic content
      were determined by spectrophotometric methods. MD and GA-based microparticles
      were non-porous and spherical, while SMP-based ones were irregularly shaped. The
      process of spray drying Prokupac GSE using these three carriers produced powders
      with low water activity (0.24-0.28), good powder characteristics, high yields,
      and solubility higher than 90%. The obtained dissolution/release profiles
      indicated prolonged release of anthocyanins and phenolic compounds in different
      mediums, especially from GSE/GA microparticles. These results have shown that
      grape skin as the main by-product of wine production could be used as a source of
      natural colorants and bioactive compounds, and microencapsulation as a promising
      technique for the protection of these compounds, their stabilization in longer
      periods and prolonged release.

PMID- 29051637
TI  - Characterization of molecular structures of theaflavins and the interactions with
      bovine serum albumin.
AB  - In this study, theaflavins (TF1, TF2A, TF2B and TF3) were prepared from black tea
      and their interaction with bovine serum albumin (BSA) was explored by
      fluorescence and CD spectroscopy. The results showed that the structures of
      theaflavins exhibited significant effects on the binding/quenching process, and
      the binding affinity increased with the increase of molecular weight of
      theaflavins and the presence of galloyl moiety. The quenching effects showed a
      sequence as TF3 > TF2A > TF2B > TF1, demonstrating the important role of the
      galloyl moiety on the C-3 position of theaflavins. CD spectra indicated that TF3
      in high concentration could change the skeleton structure of BSA and induce the
      unfolding of BSA secondary structure. The present results provide a new
      perspective for better understanding of the likely physiological fate of
      theaflavins and help to control the functional characteristics of food.

PMID- 29051639
TI  - Organic acids as a freshness indicator for tofu (soybean curd).
AB  - The aim of this study was to evaluate organic acids as potential indicators of
      tofu freshness. To achieve this, relationships between organic acids
      concentrations and the growth of microorganisms in fresh tofu were investigated.
      The levels of microorganisms (total bacterial count) and organic acids (phytic
      acid, oxalic acid, citric acid, lactic acid, formic acid and acetic acid) were
      analyzed in tofu (packed and unpacked) every 3 days during 15 days of storage at
      different temperatures (4, 10, and 25  degrees C). Organic acids were analyzed by
      high performance liquid chromatography and microbial analysis was conducted by
      plate counting method. The levels of oxalic acid, citric acid and formic acid
      decreased significantly during the storage period, while the levels of lactic
      acid and acetic acid increased significantly when stored at 10  degrees C. The
      acetic, lactic and formic acids showed significant correlation to the levels of
      microorganisms in packed tofu, suggesting the use of these organic acids as
      potential freshness quality indicators of tofu. Current study demonstrated the
      effective way of predicting freshness of tofu by utilizing organic acid analysis,
      as opposed to traditional method relying on microbial count.

PMID- 29051638
TI  - Physical characterization of whole and skim dried milk powders.
AB  - The lack of updated knowledge about the physical properties of milk powders aimed
      us to evaluate selected physical properties (water activity, particle size,
      density, flowability, solubility and colour) of eleven skim and whole milk
      powders produced in Europe. These physical properties are crucial both for the
      management of milk powder during the final steps of the drying process, and for
      their use as food ingredients. In general, except for the values of water
      activity, the physical properties of skim and whole milk powders are very
      different. Particle sizes of the spray-dried skim milk powders, measured as
      volume and surface mean diameter were significantly lower than that of the whole
      milk powders, while the roller dried sample showed the largest particle size. For
      all the samples the size distribution was quite narrow, with a span value less
      than 2. The loose density of skim milk powders was significantly higher than
      whole milk powders (541.36 vs 449.75 kg/m3). Flowability, measured by Hausner
      ratio and Carr's index indicators, ranged from passable to poor when evaluated
      according to pharmaceutical criteria. The insolubility index of the spray-dried
      skim and whole milk powders, measured as weight of the sediment (from 0.5 to 34.8
      mg), allowed a good discrimination of the samples. Colour analysis underlined the
      relevant contribution of fat content and particle size, resulted in higher
      lightness (L*) for skim milk powder than whole milk powder, which, on the other
      hand, showed higher yellowness (b*) and lower greenness (-a*). In conclusion a
      detailed knowledge of functional properties of milk powders may allow the dairy
      to tailor the products to the user and help the food processor to perform a
      targeted choice according to the intended use.

PMID- 29051640
TI  - Atta (whole wheat flour) with multi-wholegrains: flour characterization,
      nutritional profiling and evaluation of chapati making quality.
AB  - Non-wheat grains, complementing the nutritional profile of wheat were utilized
      for the development of atta with multi-whole grains. Based on the dimensions,
      selected grains were segregated and the grinding techniques were applied for the
      production of multi whole grains flour. Multi whole grains flour was replaced
      with whole wheat flour to obtain five different formulations and further compared
      with control atta. With the increase in incorporation of the multi whole grain
      flours reduction in brightness (L*) from 79.73 to 78.47 and redness (a*) from
      2.47 to 12.12 while the increase in yellowness (b*) was observed (12.10-12.70).
      Protein content increased from 13.44 to 14.83% while dietary fibre content was
      also found to be increased in all the formulations compared to control atta. Ash
      content, an indicator of mineral content showed an increasing trend with the
      increase in the level of non-wheat grains. Shear force required for tearing the
      chapatis at 0 h was observed to be in the range of 15.6 and 10.1 N and moisture
      content between 32.6 and 30.4%. Mineral analysis carried out for the 10%
      replacement showed an increase in the level of the estimated minerals. An overall
      eating quality of the chapatis was found to be acceptable up to 10% replacement
      compared to control atta chapati.

PMID- 29051641
TI  - Optimization of spray drying process parameters for tucupi powder using the
      response surface methodology.
AB  - A completely randomized 23 factorial experimental design was used to optimize the
      process parameters for obtaining tucupi powder through spray drying. The effects
      of the process variables [inlet air temperature (IT), feed flow rate (FR), and
      maltodextrin concentration (MD)] on the product properties [moisture, water
      activity (aw), hygroscopicity, water absorption index (WAI), water solubility
      index (WSI), total color difference (DeltaE*), and beta-carotene content] were
      studied using the response surface methodology (RSM) and linear perturbation
      plot. In addition, scanning electron microscopy (SEM) images were obtained of the
      product. According to ANOVA and the regression coefficients (R2 > 0.90), the RSM
      models were significant and IT was the variable with the greatest impact on most
      of the responses. SEM shows that the powders obtained with higher IT and MD and
      lower FR were more uniform, with smooth and intact surfaces. The optimal
      conditions estimated for the process were IT at 214  degrees C, FR at 8.67
      mL/min, and MD at 27%. Under those conditions, the product's minimum values of
      moisture (9.56 g/100 g), aw (0.101), hygroscopicity (37.45% d.b.), and DeltaE*
      (17.05) and maximum values of WAI (6.68 g/g d.b.), WSI (84.77%), and beta
      carotene (13.72 ug/g) were estimated.

PMID- 29051642
TI  - Microbiological and chemical changes of shrimp Acetes vulgaris during Kapi
      production.
AB  - Microbiological and chemical changes in shrimp Acetes vulgaris during production
      of Kapi (salted shrimp paste of Thailand) including salting, drying and
      fermentation were monitored. Moisture content of samples decreased rapidly after
      salting and drying steps. The lower water activity was found in the final product
      (0.694). The pH decreased within the first 10 days of fermentation and
      continuously increased as fermentation progressed. Protein underwent degradation
      throughout Kapi production as indicated by increasing TCA-soluble peptides and
      degree of hydrolysis. The increases in peroxide value as well as thiobarbituric
      acid reactive substances value revealed that lipid oxidation occurred throughout
      all processes. Total viable count, halophilic, proteolytic and lipolytic bacteria
      counts increased continuously during Kapi production, while lactic acid bacteria
      count slightly decreased at the final stage of fermentation. Thus, proteolysis
      and lipolysis took place throughout Kapi production, and contributed to the
      characteristics of finished product. These changes were governed by both
      endogenous and microbial enzymes.

PMID- 29051643
TI  - Synthesis, characteristics and evaluation of antioxidant activity of [1-(tannin
      ether)-ethyl]stearate.
AB  - The [1-(tannin-ether)-ethyl]stearate (TEES) was synthesized by two-stage process
      successfully. 1-Chloroethyl tannin ether (CTE), as an intermediate, was initially
      prepared with tannic acid (TA) and paraldehyde. Then, the TEES was synthesized by
      sodium stearate and CTE in the presence of FeCl3-PEG-400 as phase-transfer
      catalyst. Synthetic conditions were optimized. The structural characteristics of
      TEES were analyzed by FTIR, 1H NMR and UV-vis techniques. And the thermal
      stability of TEES was investigated. Moreover, the antioxidant activity of TEES
      for linseed oil was evaluated and compared with other substance such as TA and
      butylated hydroxyanisole (BHA). The results showed that the yield reached 88.19
      wt% (theoretical value: 88.80 wt%, relative deviation: 0.80 +/- 0.34%) under the
      optimized condition, in which the ratio of TA: FeCl3: PEG-400 was 1 g: 0.09 g:
      0.693 mL, the reaction temperature and time was 75  degrees C and 240 min,
      respectively. The antioxidant activity of TEES was higher than TA and comparable
      to BHA in linseed oil. The POV of oil samples with TEES, TA and BHA were 63.4,
      201.3 and 84.2 meq/kg after 20 days, respectively. The reason of this was relate
      to the better oil solubility of TEES and its unique structure. More importantly,
      the interaction between the TEES and SC was weaker than that of TA and SC by the
      fluorescence experiment.

PMID- 29051644
TI  - Chemical compositions, antioxidant and antimicrobial properties of Ziziphora
      clinopodioides Lam. essential oils collected from different parts of Iran.
AB  - The aims of the present study were to investigate chemical compositions,
      antioxidant and antimicrobial properties of Ziziphora clinopodioides essential
      oils (ZEOs) collected from four provinces in western Iran (Ilam, Lorestan,
      Kermanshah and Kurdestan). Carvacrol was the most abundant constituent in the
      flower, stem and leaf oil samples of Ilam, Lorestan and Kermanshah regions by
      73.12-74.29%, 66.47-66.89% and 65.11-65.32%, respectively. The most abundant
      components in Kurdestan sample were thymol (55.32-55.60%), followed by gamma
      terpinene (24.45-24.56%), p-cymene (10.21-10.25%) and alpha-terpinene (2.75
      2.77%). The ZEO inhibited the growth of Listeria monocytogenes, Salmonella
      typhimurium, Escherichia coli O157:H7, Bacillus subtilis, Bacillus cereus and
      Staphylococcus aureus at MIC values between 0.03 and 0.04%. Kermanshah oil sample
      had a higher 1,1-diphenyl-2-picrylhydrazyl radical scavenging (0.30-0.31 mg/ml),
      ability to prevent the bleaching of beta-carotene (0.09-0.1 mg/ml), ferric
      reducing power (0.40-0.42 mg/ml) and thiobarbituric acid (0.004-0.006 Meq of
      malondialdehyde/g) values than that of ZEOs from Ilam, Kurdestan and Lorestan.
      The strong in vitro antimicrobial and antioxidant activities supports the
      traditional use of ZEO in the treatments of gastrointestinal diseases.

PMID- 29051645
TI  - Adherence potential of indigenous lactic acid bacterial isolates obtained from
      fermented foods of Western Himalayas to intestinal epithelial Caco-2 and HT-29
      cell lines.
AB  - The adherence of bacteria to epithelial cells and mucosal surfaces is a
      prerequisite for their colonization in the gut and a key criterion for the
      selection of probiotics. In this study, the eleven indigenous lactic acid
      bacterial isolates obtained from traditional fermented foods of Western Himalayas
      were screened for their adherence potential to intestinal epithelial cell lines.
      The level of adherence of eleven indigenous isolates to Caco-2 and HT-29 cell
      lines varied from 2.45 +/- 0.5 to 9.55 +/- 0.76% and 4.11 +/- 0.68 to 12.88 +/-
      0.63%, respectively. Percent adhesion of indigenous isolates to Caco-2 cells was
      relatively lower as compared to HT-29 cells. Indigenous isolate AdF10 (L.
      plantarum) was found to be the most adhesive to HT-29 and Caco-2 with
      corresponding figures of 12.88 +/- 0.63 and 9.55 +/- 0.76%, respectively. AdF4
      (B. coagulans) was found to be least adhesive to HT-29 and Caco-2 with respective
      corresponding figures of 4.11 +/- 0.68 and 2.45 +/- 0.5%. Based on the percent
      adhesion values, indigenous isolate AdF10 (L. plantarum) was comparable to the
      reference probiotic strain L. rhamnosus GG-ATCC-53103 with respective adhesion of
      13.5 +/- 1.19 and 10.33 +/- 0.64% to HT-29 and Caco-2 cell lines. It was closely
      followed by indigenous isolates AdF5 (L. plantarum) and AdF6 (L. plantarum);
      thus, indicating their potential as a promising probiotic candidates.

PMID- 29051646
TI  - Effect of fiber blends, total solids, heat treatment, whey protein concentrate
      and stage of sugar incorporation on dietary fiber-fortified Kheer.
AB  - Owing to the proven beneficial role of dietary fiber (DF) on human health,
      feasibility of incorporating commercially available soluble and insoluble DF
      preparations into rice-milk-pudding (kheer, a popular Indian delicacy) was
      studied through process modification. The novel approach of preparing reduced fat
      DF-fortified-kheer (DFFK) by developing liquid/cream phase and particulate/rice
      phase separately, and subsequently blending the two was developed. The major
      processing variables studied were total solids (TS) in the liquid phase, type of
      fiber blend, flavor-simulation through heat treatment or added whey protein, and
      the presence of sugar in water for pre-cooking of rice. Reduced fat DFFK made
      from three different pre-standardized fiber blends was quite acceptable to the
      sensory panel (overall rating 7.5). With increasing TS in milk up to 16.5%,
      sensory acceptability of DFFK increased. There was a small but perceivable
      improvement in the flavour of DFFK when precooking of rice was carried out in
      sweetened water. Reduced fat DFFK from different fiber blends was found to be
      reasonably close to conventional kheer. DFFK prepared from Blend-I provided 3.31
      g dietary fiber/100 kcal (suitable for the claim "High-in-Fiber") with 38.71%
      Reduced-Fat. With the developed process of fortification of kheer with DF, it is
      possible to reduce fat (and thus calories) to cater to the needs of consumers
      seeking good health.

PMID- 29051647
TI  - High pressure processing and post-high pressure storage induce the change of
      polyglutamyl folate and total folate from different legumes.
AB  - The aim of this work was to study the effect of high pressure processing (HPP)
      and post-HPP cold storage on the distribution of polyglutamyl and monoglutamyl
      folate and the absolute concentration of total folate in green beans, yardlong
      beans and winged beans using a validated ultra-high performance liquid
      chromatography-tandem mass spectrometry method. The results showed that HPP led
      to the deglutamylation of polyglutamyl folate to monoglutamyl folate in all of
      the investigated beans. The degree of deglutamylation was increased with
      enhancing processing pressure and extending holding time. During HPP, significant
      loss of total folate was observed under 600 MPa/10 min treatment. Uniquely 300
      MPa/5 min and 450 MPa/5 min could significantly release more folate from yardlong
      beans and green beans matrix. During the following cold-storage, the
      deglutamylation keep progressing. For those untreated beans, no significant
      deglutamylation and total folate loss was observed during cold storage for
      yardlong beans and green beans while there is slight change for the total folate
      in winged beans. For those HPP treated beans, total folate loss followed the
      first order kinetics over the storage. The rate constant of degradation was
      positively proportional to the applied pressure, holding time and the proportion
      of monoglutamyl folate. This research provided a reference for understanding the
      deglutamylation of polyglutamyl folate and folate loss during HPP treatment and
      further shelf life.

PMID- 29051648
TI  - Effects of xanthan gum and HPMC on physicochemical and microstructure properties
      of sponge cakes during storage.
AB  - The effects of xanthan gum (XG) and hydroxypropyl methylcellulose (HPMC) in
      sponge cakes were studied. Hydrocolloids enhanced the thickening effect in batter
      that affected the textural attributes of sponge cakes. During storage, the
      structural changes in XG-cake resulted in higher hardness compared to HPMC-cake.
      Similar to XG, HPMC also contributed moistness to cake. The moisture loss of cake
      containing XG was slower than HPMC-cake. FTIR study showed absorption of OH at
      region of 3600-2900 cm-1 that explained the strong interaction of water in cake
      containing XG compared to other cake formulations.

PMID- 29051649
TI  - Changes in functional properties and in vitro bioaccessibilities of beta-carotene
      and lutein after extrusion processing.
AB  - In this research, carrot pulp was added to traditional snack made from corn-grit.
      As the biological activity of carotenoids in the body depends on their
      bioaccessibility, change in carotenoid bioaccessibility during extrusion
      processing was investigated. In addition, phenolic content, antioxidant activity,
      beta-carotene and lutein contents were investigated before and after the
      extrusion process. Two different temperature profiles were used for extrusion
      process. In-vitro bioaccessibilities of beta-carotene and lutein increased by
      extrusion, beta-carotene at both temperature profiles while lutein only at higher
      temperature profile. Extrusion decreased the antioxidant activity, total
      phenolic, beta-carotene and lutein contents. Results suggest that even though
      amount of functional components decrease, in vitro bioaccessibility could be
      enhanced by extrusion. Therefore, carrot pulp can successfully be added as a
      functional ingredient to extrudated.

PMID- 29051650
TI  - Optimization of the antioxidant polyphenolic compounds extraction of yellow
      passion fruit seeds (Passiflora edulis Sims) by response surface methodology.
AB  - The conditions for the solid-liquid extraction of the antioxidant polyphenol
      compounds from yellow passion fruit seeds were optimized by response surface
      methodology with the following variables as the extraction parameters: extraction
      time (12.8-147.2 min), ethanol concentration (13-97%), and temperature (16.4-83.6
      degrees C). The polyphenol content and antioxidant capacity, which were assessed
      by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, oxygen radical
      absorbance capacity, beta-carotene bleaching assay, and ferric reducing
      antioxidant power assay, were considered dependent variables. The association of
      the dependent variables was effective for explaining the effect of the
      independent variables within a determination coefficient (R2) range of 0.88-0.96.
      A moderate-to-strong correlation for the polyphenol content and antioxidant
      capacity by the investigated methods was established, and optimized conditions
      were employed to maximize this response. Extraction was carried out at 80 
      degrees C using 70% ethanol concentration for 30 min, which was the most
      efficient condition to obtain an extract with high concentrations of polyphenolic
      compounds (3.12 g gallic acid equivalent/100 g seed dry basis) and a strong
      antioxidant capacity. The stilbene piceatannol was the major compound identified
      by liquid chromatography-electrospray ionization-tandem mass spectrometry (3.68
      g/100 g seed dry basis). These results reinforce that agro-industrial waste
      demonstrates potential as a source of bioactive compounds, with implications in
      human health as well as in food and chemical industries.

PMID- 29051651
TI  - Use of high pressure technology for the development of novel jam and its quality
      evaluation during storage.
AB  - Jam like product was prepared using high pressure (HP) processing technology and
      was compared with thermally processed one for quality attributes. Strawberry pulp
      was mixed with pectin (1%) and sugar and packed in low density polyethylene
      pouches (50 g pack size) and processed at 200, 400 and 600 MPa for 30 min at 50 
      degrees C. Ascorbic acid, anthocyanins, phenolics, flavonoids and antioxidant
      activities were found to be significantly retained to a better extent in HP
      processed jams as compared to thermally processed one. The CIE L*, a* and b*
      values decreased significantly with increase in pressure, the decrease being of
      much lesser extent compared to thermally processed one. Increase in pressure was
      found to increase the sensory attributes for colour, appearance, flavour, texture
      and overall acceptability significantly; however, the scores were comparatively
      lesser than that of thermally processed jam. The sample processed at 600 MPa
      showed a shelf-life of 3 months on the basis of physico-chemical, sensory and
      microbial attributes when stored at ambient storage conditions (28 +/- 5  degrees
      C).

PMID- 29051652
TI  - Making good use of the byproducts of cultivation: green synthesis and
      antibacterial effects of silver nanoparticles using the leaf extract of
      blueberry.
AB  - In this study, we made an effort to use blueberry leaves extract as a reducing
      and a capping agent to biosynthesize silver nanoparticles (AgNPs). The successful
      formation of AgNPs was confirmed with UV-visible spectroscopy, transmission
      electron microscopy, Fourier transform infrared spectroscopy and X-ray
      diffraction. Furthermore, their antimicrobial activities against four kinds of
      multi drug resistant clinical pathogens and aquatic pathogens were investigated.
      The results showed that as-prepared AgNPs exhibited broad-spectrum antibacterial
      activities. The antibacterial effects of the AgNPs based on the structural damage
      and DNA degradation of the tested bacteria were also studied. The green synthesis
      of AgNPs using blueberry leaf extract, which provided a new idea on the use of
      the byproducts of blueberry harvesting.

PMID- 29051653
TI  - Effect of genotypes and growth locations on composition and functional properties
      of amadumbe flours.
AB  - Amadumbe, known as taro is a traditional crop mainly grown for subsistence in
      Southern Africa. In this study, chemical composition and functional properties of
      nine amadumbe genotypes grown at two distinct locations were investigated.
      Carbohydrate contents (73-81%) of amadumbe genotypes were substantially high and
      varied with growth location. Protein contents ranged from 8-12% and fat was very
      low (less 1%) in all genotypes. Major minerals in flours were K, P, Mg and Ca,
      but these were present at varying levels depending on growth locations. Amadumbe
      flours showed slightly low mucilage contents (6-9%) across genotypes. However,
      genotypes with higher mucilage contents generally had higher water absorption
      capacities irrespective of growth locations. Genotype and growth location
      significantly affected the pasting properties of amadumbe flours. Peak
      viscosities varied between 83-242 RVU among genotypes. The pasting temperature of
      the genotypes were fairly high 87-94  degrees C across genotypes. This study data
      suggests that differences in environmental temperatures and amounts of rain falls
      received at growth location during the growing season could be some of the
      factors responsible for the variations in flour composition and consequently
      their functionality. Findings from this study are important for future
      improvement programme and for food application of amadumbe flour.

PMID- 29051654
TI  - Characterization of dietary constituents and antioxidant capacity of Tropaeolum
      pentaphyllum Lam.
AB  - The aim of this study was to evaluate the nutritional content and antioxidant
      capacity of the tubers, leaves and, flowers of the species Tropaeolum
      pentaphyllum Lam. The three parts of the plant were analyzed by physicochemical
      methods, atomic absorption spectrometry, spectrophotometric and chromatographic
      techniques. The tubers, leaves, and flowers exhibited significant differences in
      all parameters evaluated. The leaves showed significantly higher values of
      protein (16.28 +/- 0.02 g/100 g), total dietary fiber (27.78 +/- 0.15 g/100 g)
      and quercetin (3798.61 +/- 37.57 ug/g) when compared to the tubers and flowers.
      The study revealed a potential content of the protein, dietary fiber, and
      flavonoids the species Tropaeolum pentaphyllum, when compared with the sweet
      potatoes leaves (Ipomoea batatas L.). In addition, the antioxidant activities of
      leaves and flowers were also higher measured by ABTS (2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl), and
      TRAP (total radical-trapping antioxidant potential) methods. Tropaeolum
      pentaphyllum have high nutritional potential that can be exploited to improve
      nutritional value of various food products.

PMID- 29051655
TI  - Evaluation of nutritional quality and antioxidant potential of pigeonpea
      genotypes.
AB  - Three released cultivars, forty four advance breeding lines and three wild
      species of pigeonpea (Cajanus cajan L. Millsp) were evaluated for nutritional,
      antinutritional traits and antioxidant potential so as to identify promising
      genotypes. The average content of total soluble sugars, starch and total soluble
      proteins was found to be 43.66, 360.51 and 204.54 mg/g, respectively. Antioxidant
      potential in terms of free radical scavenging activity (DPPH), ferric reducing
      antioxidant power (FRAP), reducing power, hydroxyl radical scavenging activity
      and superoxide anion radical scavenging activity was estimated. The diversity was
      observed in genotypes with all the traits. AL 1960, AL 2000, AL 2009 and AL 2046
      had high total soluble proteins, medium antinutritional factors and good
      antioxidant potential. AL 201, AL 1931, AL 1932, AL 1960, AL 2046, AL 2049 and AL
      2060 had good nutritional value as protein and starch content ranged from 20 to
      23 and 42 to 52%, respectively. Wild species C. scarabaeoides 1CP15683/W15 had
      lower carbohydrates, proteins, and antinutritional traits while high antioxidant
      potential due to high total phenols, DPPH, FRAP and reducing power. The diversity
      observed in genotypes with all the traits could be further used to develop
      nutritionally important genotypes.

PMID- 29051656
TI  - Antimicrobial resistance in diarrheagenic Escherichia coli from ready-to-eat
      foods.
AB  - Certain subgroups of Escherichia coli have congenital or acquired virulence
      properties that allow them to cause a wide spectrum of disease. The aim of this
      study was to investigate the occurrence of diarrheagenic E. coli strains in ready
      to-eat (RTE) foods produced in institutional, commercial and hotel restaurants in
      Salvador, Brazil. The presence of virulent isolates and antimicrobial resistance
      were evaluated. Four hundred forty-six samples were collected and grouped into
      cereals and vegetables, meat-based preparations, cooked salads, raw salads,
      garnishes, soups and sauces, desserts and juices. E. coli were detected using the
      most probable number method, the presence of virulence factors in isolates was
      determined by polymerase chain reaction (PCR) assays, and antibiotic resistance
      was analyzed using the disc diffusion method. In total, 15 isolates (3.1%) of E.
      coli were recovered; raw salads had the highest detection rate, 1.4%, followed by
      cooked salads, 0.8%; meat-based preparations, 0.4%; and cereals and vegetables,
      0.4%. PCR assays showed that none of the isolates had the virulence genes cnf1,
      cnf2, eae, sta, lt1, stx1, stx2 or cdtB. The isolates showed resistance to nine
      antibiotics of the 15 tested, and the highest levels of resistance were found for
      sulfamethoxazole/trimethoprim, tetracycline, ampicillin, and chloramphenicol
      (13.3% of isolates for each antibiotic). One isolate from cooked salad had
      plasmid-mediated multidrug resistance to tetracycline,
      trimethoprim/sulfamethoxazole, ampicillin and chloramphenicol. These results
      suggest that RTE foods, especially raw salads, can be reservoirs of E. coli and
      facilitate the spread of antibiotic resistance genes to the gastrointestinal
      microbiota of humans.

PMID- 29051657
TI  - The enhancement of pistachio green hull extract functionality via nanoliposomal
      formulation: studying in soybean oil.
AB  - Phenolic compounds of pistachio green hull extract (PGHE) were incorporated into
      nanoliposomes (NLs). The NLs were prepared with different concentrations of
      phenolic compounds of PGHE (500, 750 and 1000 ppm) and particle size,
      polydispersity index (PDI), zeta potential and encapsulation efficiency (EE) were
      investigated. The antioxidant activity of free and incorporated phenolic
      compounds of PGHE were evaluated in soybean oil during 39 days of storage by
      measuring peroxide (PV), thiobarbituric acid (TBA) values and color. The total
      phenolic content and IC50 (DPPH assay) of PGHE were 614.91 +/- 0.45 mg gallic
      acid equivalent/g fresh weight of extract and 10 +/- 0.05 MUg/ml extract,
      respectively. The prepared NLs had 101.86-105.81 nm size and PDI = 0.202-0.235.
      The zeta potential value of NLs varied between -47.7 and -52.3 mV. The highest EE
      (32.47%) was observed for NLs containing 1000 ppm of phenolic compounds. The
      lowest PV and TBA values were related to free phenolic compounds at 500 mg/kg
      oil. In comparison with free phenolic compounds, loaded NLs had lower antioxidant
      activity, but encapsulation could improve the stability, gradual release and
      solubility of phenolic compounds in soybean oil. The color of NLs containing oil
      samples remained constant during the storage, but free phenolic compounds changed
      the oil's color. All concentrations of free and incorporated phenolic compounds
      had also higher antioxidant activity than BHT. Finally, 500 ppm of phenolic
      compounds of PGHE in its incorporated forms could be recommended as a substitute
      for synthetic antioxidant in soybean oil.

PMID- 29051658
TI  - Reverse micellar extraction of lactoferrin from its synthetic solution using
      CTAB/n-heptanol system.
AB  - The partitioning of Lactoferrin (LF) into the reverse micellar phase formed by a
      cationic surfactant, cetyltrimethylammonium bromide (CTAB) in n-heptanol from the
      synthetic solution of LF was studied. The solubilization behaviour of LF into the
      reverse micellar phase and back extraction using a fresh stripping phase were
      improved by studying the effect of processing parameters, including surfactant
      concentration, solution pH, electrolyte salt concentration and addition of
      alcohol as co-solvent. Forward extraction of 100% was achieved at CTAB
      concentration of 50 mM in n-heptanol solvent, pH of 10 and 1 M NaCl. The
      electrostatic force and hydrophobic interaction have major influence on LF
      extraction during forward and back extraction respectively. The size of the
      reverse micelles and their corresponding water content were measured at different
      operating conditions to assess their role on the LF extraction. The present
      reverse micellar system has potential to solubilise almost all the LF into the
      reverse micelles during forward extraction and could able to allow back
      extraction from the reverse micellar phase with addition of small amount of co
      solvent.

PMID- 29051659
TI  - In vitro assessment of bio-augmented minerals from peanut oil cakes fermented by
      Aspergillus oryzae through Caco-2 cells.
AB  - Present study was carried out to assess the significances of solid state
      fermentation of peanut oil cakes (POC) by Aspergillus oryzae on in vitro
      bioavailability of minerals (iron, zinc and calcium) and cellular transport,
      retention and uptake from POC through Caco-2 cells. Bioavailability of iron, zinc
      and calcium of POC was examined by means of a combined simulated gastrointestinal
      digestion/Caco-2 cell system. Bio-augmentation of minerals of fermented POC
      attributed a positive, statistically significant increased influence on minerals
      retention, transport and uptake values when compared with that of respective
      inorganic salts as reference. Results revealed increased cellular ferritin
      content from fermented POC digests than the digests of free form of respective
      inorganic salt. In prospect of the present investigation the fermented POC
      samples showed significantly higher iron, zinc and calcium bioavailability and
      enormous possible health benefits.

PMID- 29051660
TI  - Determination of the difference on color changes of watermelons by laser light
      backscattering imaging.
AB  - The potential of laser light backscattering imaging was investigated for
      monitoring color parameters of seeded and seedless watermelons during storage.
      Two watermelon cultivars were harvested and stored for 3 weeks with seven
      measuring storage days (0, 4, 8, 12, 15, 18, and 21). The color parameters of
      watermelons were monitored using the conventional colorimetric methods (L*, a*,
      b*, C*, H*, and ?E*) and laser light backscattering imaging system. A laser diode
      emitting at 658 nm and 30 mW power was used as a light source to obtain the
      backscattering image. The backscattering images were evaluated by the extraction
      of backscattering parameters based on the mean pixel values. The results showed
      that a good color prediction was achieved by the seedless watermelon with the R2
      are all above 0.900. Thus, the application of the laser light backscattering
      imaging can be used for evaluating the color parameters of watermelons during the
      storage period.

PMID- 29051661
TI  - Effects of hydrogen peroxide, modified atmosphere and their combination on
      quality of minimally processed cluster beans.
AB  - The aim of this study was to determine the potential of hydrogen peroxide (H2O2)
      and modified atmosphere packaging (MAP) on quality of fresh-cut cluster beans.
      Fresh-cut cluster beans were dipped in a solution of 2% H2O2 for 2 min, packed in
      an atmosphere of (5% O2, 10% CO2, 85% N2) and stored in polypropylene bags at 5 
      degrees C for 35 days. Passive MAP was created by consuming O2 and producing CO2
      by fresh-cut cluster beans. The combined effect of H2O2 and MAP on physico
      chemical analysis (Headspace gas, weight loss, chlorophyll, hardness and color),
      microbial quality (mesophilic aerobics and yeasts and molds) and sensory analysis
      were studied. Chemical treatment and MAP both are equally effective in extending
      the shelf life at 5  degrees C for 28 days. Hence, MAP can be an alternative for
      chemical treatment to achieve a shelf life of 28 days for fresh-cut cluster
      beans. Control samples, without chemical treatment and modified atmosphere,
      stored at 5  degrees C were spoiled after 14 days. Chemical treatment followed by
      MAP underwent minimum changes in weight, chlorophyll, hardness and color of fresh
      cut cluster beans. Combination treatment gives a storage life of 35 days.

PMID- 29051662
TI  - Improving phenolic bioactive-linked anti-hyperglycemic functions of dark
      germinated barley sprouts (Hordeum vulgare L.) using seed elicitation strategy.
AB  - Sprouts of cereal grains, such as barley (Hordeum vulgare L.), are a good source
      of beneficial phenolic bioactives. Such health relevant phenolic bioactives of
      cereal sprouts can be targeted to manage chronic hyperglycemia and oxidative
      stress commonly associated with type 2 diabetes (T2D). Therefore improving
      phenolic bioactives by stimulating plant endogenous defense responses such as
      protective pentose phosphate pathway (PPP) during sprouting has significant
      merit. Based on this metabolic rationale, this study aimed to enhance phenolic
      bioactives and associated antioxidant and anti-hyperglycemic functions in dark
      germinated barley sprouts using exogenous elicitor treatments. Dark-germinated
      sprouts of two malting barley cultivars (Pinnacle and Celebration), treated with
      chitosan oligosaccharide (COS) and marine protein hydrolysate (GP), were
      evaluated. Total soluble phenolic content (TSP), phenolic acid profiles, total
      antioxidant activity (TA) and in vitro inhibitory activities of hyperglycemia
      relevant alpha-amylase and alpha-glucosidase enzymes of the dark germinated
      barley sprouts were evaluated at day 2, 4, and 6 post elicitor treatments.
      Overall, TSP content, TA, and alpha-amylase inhibitory activity of dark
      germinated barley sprouts decreased, while alpha-glucosidase inhibitory activity
      and gallic acid content increased from day 2 to day 6. Among barley cultivars,
      high phenolic antioxidant-linked anti-hyperglycemic bioactives were observed in
      Celebration. Furthermore, GP and COS seed elicitor treatments in selective doses
      improved T2D relevant phenolic-linked anti-hyperglycemic bioactives of barley
      spouts at day 6. Therefore, such seed elicitation approach can be strategically
      used to develop bioactive enriched functional food ingredients from cereal
      sprouts targeting chronic hyperglycemia and oxidative stress linked to T2D.

PMID- 29051663
TI  - kappa-Casein as a source of short-chain bioactive peptides generated by
      Lactobacillus helveticus.
AB  - This paper explores the ability of Lactobacillus helveticus strains to release
      sequences of short biologically active peptides (containing 2-10 amino acid
      residues) from casein. The proteolytic enzymes of the tested strains exhibit
      different patterns of cleavage of CN fractions. The modification of kappa-casein
      (kappa-CN) with pyrrolidone carboxylic acid inhibits the proteolytic activity of
      strains L. helveticus 141 and the reference strain (DSMZ 20075), while the
      modification with phosphothreonine inhibits enzymes of all the tested bacteria.
      The peptide sequencing analysis indicated that the examined strains produced
      functional peptides very efficiently. kappa-CN proved to be the main source of
      short peptides released by bacterial enzymes, and the hydrolysis of kappa-CN
      yielded eighty-two bioactive peptides. The hydrolysis of alphaS2-casein, alphaS1
      casein, and beta-casein yielded six, two, and one short-chain bioactive peptides,
      respectively. The isolated bioactive peptides exhibited antioxidative, opioid,
      stimulating, hypotensive, immunomodulating, antibacterial, and antithrombotic
      activities. A vast majority of the isolated bioactive peptides caused inhibition
      of the angiotensin-converting enzyme and dipeptidyl peptidase IV. The role of
      hydrolysis products as neuropeptides is also pointed out. The highest number of
      cleavage sites in kappa-casein and functional activities of short-chain peptides
      were obtained in hydrolyzates produced by L. helveticus strain T105.

PMID- 29051664
TI  - Status of the bioactive phytoceuticals during deep-fat frying of snack food using
      nutra-coconut oil.
AB  - The present study was carried out to study the physico-chemical changes that take
      place in both product and oil during the deep fat frying of a traditional savoury
      snack 'kodubale', at 120-160  degrees C for 120-600 s using coconut oil (CO) and
      nutra-coconut oil (NCO). Further, kinetic studies on moisture loss, oil uptake,
      color and degradation of beta-carotene, total polyphenol content and antioxidant
      activity for kodubale was carried out during frying as a function of temperature
      and time. The study showed that the kinetic coefficients for above parameters
      increased with temperature and time and the data obtained were well fitted with
      first order kinetic model. The results also revealed that NCO fried product
      retained major phenolic acids due to the presence of antioxidants in the NCO
      which was enriched with flaxseed oil concentrate. The fatty acids profile of oil
      extracted from products obtained by frying using NCO was characterized with
      higher omega-3 and omega-6 fatty acids content as compared to same obtained using
      CO. However, the breaking strength and sensory characteristics of CO and NCO
      fried kodubale was found to have no significant difference (p < 0.05).

PMID- 29051665
TI  - Effects of microwave heating of wheat on its functional properties and
      accelerated storage.
AB  - The effect of microwave heating wheat grains (700 W for 0-60 s) on gluten,
      farinograph, pasting properties and baking (steamed bread and biscuit) of flour
      was studied. The lipase (LA) and lipoxygenase (LOX) activities of the microwave
      treated wheat were monitored, and the accelerated storage at 35  degrees C of
      whole wheat flour was also investigated. The results showed that the gluten,
      farinograph properties and viscosity were influenced to a small extent when
      microwave treatment time was less than or equal to 20 s and the temperature of
      the grains was less than or equal to 56  degrees C. Texture profile analysis
      indicated that steamed bread made from wheat treated by microwave for 20 s was
      softer and of better quality. Microwave treatment for longer periods (>=30 s)
      increased the temperature >=68  degrees C, that damaged the gluten and made wheat
      unsuitable for making steamed bread; however, suitable for making food with lower
      gluten requirements, such as biscuits. The results obtained from enzyme activity
      and accelerated storage experiments demonstrated that microwave treatment could
      inactivate LA and LOX and extend the shelf-life.

PMID- 29051666
TI  - Enzymatic pectic oligosaccharides (POS) production from sugar beet pulp using
      response surface methodology.
AB  - Pectic oligosaccharides (POS) have been indicated as novel candidate prebiotics.
      Traditionally, POS are produced from pectin-rich by-products using a two-step
      process involving extraction of the pectin, followed by its hydrolysis into POS.
      A one-step approach, in which the POS is directly produced from the raw material,
      might provide a more efficient alternative. Thus, the main aim of this paper was
      to investigate a one-step enzymatic hydrolysis approach to directly produce POS
      from sugar beet pulp (SBP). The POS yield was investigated as a function of the
      process parameters, as well as raw material characteristics. A statistically
      based response surface methodology, using a central composite design was applied,
      to investigate the individual as well as the combined influences of the diverse
      parameters. The model was confirmed by a validation experiment, carried out at
      135 g/l substrate concentration, 0.75 FPU/g SBP enzyme concentration, 0.8 mm
      particle size and 3 h hydrolysis time. Under these conditions, a POS-rich
      hydrolysate was obtained, containing rhamnose, arabinose, galactose, xylose and
      galacturonic acid, at 0.9, 15.2, 5.1, 1.4, and 13.2 g/l, respectively, enzymes
      were added each at 20 FPU/g dry matter (DM).

PMID- 29051667
TI  - Free amino acids profile of Polish and Slovak honeys based on LC-MS/MS method
      without the prior derivatisation.
AB  - LC-MS/MS method was applied for determination of free amino acids in honey
      without derivatisation steps. Twenty free amino acids including aspartic acid,
      asparagine, glutamic acid, glutamine, alanine, arginine, glycine, leucine,
      histidine, hydroxyproline, isoleucine, lysine, methionine, phenylalanine,
      proline, serine, threonine, tryptophan, valine and ornithine were analyzed in
      thirty honey samples from Poland and Slovakia. The analysis covered: acacia,
      lime, rape, multifloral and forest types of honey. Applied method was
      characterized to had good sensitivity with limit of detection ranged from 3.0
      ng/cm3 for valine to 13.0 ng/cm3 for hydroxyproline. Average content of proline
      (main amino acid component in honey) ranged from 151.46 MUg/g (rape honey from
      Slovakia) to 389.66 MUg/g for forest honey (honeydew honey) from Poland. In
      analyzed honeys large quantities of glutamine, glutamic acid, lysine,
      phenylalanine, asparagine, alanine, and valine were also found.

PMID- 29051668
TI  - Culture broth of Ganoderma lucidum exhibited antioxidant, antibacterial and alpha
      amylase inhibitory activities.
AB  - Culture broth of Ganoderma lucidum was determined for antioxidant, antibacterial
      and alpha-amylase inhibitory activities. The culture broth contained protein as
      determined by Bradford method equaled to 0.2 mg/ml and total phenol content as
      0.078 mg GAE/mg protein (0.557 mg GAE/g extract). It exhibited radicals
      scavenging activities against ABTS+. and DPPH. radicals with a half maximal
      inhibitory concentration (IC50) less than 1.70 +/- 0.02 and 2.28 +/- 0.02 ug
      protein/ml, respectively and reducing power equaled to 4.38 +/- 0.02 umol
      Trolox/ug protein as investigated by ferric ion reducing antioxidant power
      method. The culture broth experimented into two approached; (1) treated with
      pronase and (2) filtered through a membrane with 10 kDa molecular weight cut-off
      (MWCO). The pronase-treated culture broth exhibited insignificant lower
      antioxidant activities, but the retained culture broth 10 kDa MWCO resulted in
      significant decrease in antioxidant activities suggesting that the small proteins
      might play the key role in antioxidant activity. The culture broth could protect
      DNA damage from hydroxyl radicals (.OH) generated by Fenton's reaction. This
      culture broth showed antibacterial activity towards pathogenic strains
      Staphylococcus epidermidis and Pseudomonas aeruginosa and also had an interesting
      alpha-amylase inhibitory activity. This study suggested that apart from the
      fruiting bodies and the mycelial of G. lucidum, its culture broth also had
      potential applications as a value-added ingredient in the product such as in
      cosmetics and in nutraceuticals.

PMID- 29051669
TI  - beta-Carotene nanodispersions synthesis by three-component stabilizer system
      using mixture design.
AB  - In current research, simple centroid mixture design was applied to evaluate the
      interaction effects between three selected food grade stabilizers, namely, Tween
      80, gelatine and pectin as stabilizing system in the formation of carotenoid
      nanoparticles through solvent displacement process. Both, particle size and beta
      carotene loss of produced nanodispersions, as selected response factors, special
      cubic regression models with acceptable determination coefficient (>90%) was
      obtained. The multiple response optimization analysis showed that the overall
      optimum concentration for stabilizers will be 35% w/w Tween 80, 46% w/w gelatine
      and 19% w/w pectin, which led to the production of beta-carotene nanoparticles of
      spherical shape with minimum particle size of 155.8 nm and carotenoids loss of
      25.3% w/w.

PMID- 29051670
TI  - Effect of brewing conditions on antioxidant properties of rosehip tea beverage:
      study by response surface methodology.
AB  - The aim of this study was to investigate the effects of brewing conditions
      (infusion time and temperature) on the antioxidant properties of rosehip tea
      beverage. The ascorbic acid content, total phenolic content (TPC), and ferric
      reducing antioxidant power (FRAP) of rosehip tea beverage were analysed. A two
      factor and three-level central composite design was applied to evaluate the
      effects of the variables on the responses. The best quadratic models were
      obtained for all responses. The generated models were validated under the optimal
      conditions. At the optimal conditions, the rosehip tea beverage had 3.15 mg 100
      mL-1 of ascorbic acid, 61.44 mg 100 mL-1 of TPC, and 2591 umol of FRAP. The best
      brewing conditions for the rosehip tea beverage were found to be an infusion time
      of 6-8 min at temperatures of 84-86  degrees C.

PMID- 29051671
TI  - Effect of drying process assisted by high-pressure impregnation on protein
      quality and digestibility in red abalone (Haliotis rufescens).
AB  - Abalone (Haliotis spp.) is an exotic seafood product recognized as a protein
      source of high biological value. Traditional methods used to preserve foods such
      as drying technology can affect their nutritional quality (protein quality and
      digestibility). A 28-day rat feeding study was conducted to evaluate the effects
      of the drying process assisted by high-pressure impregnation (HPI) (350, 450, and
      500 MPa * 5 min) on chemical proximate and amino acid compositions and
      nutritional parameters, such as protein efficiency ratio (PER), true
      digestibility (TD), net protein ratio, and protein digestibility corrected amino
      acid score (PDCAAS) of dried abalone. The HPI-assisted drying process ensured
      excellent protein quality based on PER values, regardless of the pressure level.
      At 350 and 500 MPa, the HPI-assisted drying process had no negative effect on TD
      and PDCAAS then, based on nutritional parameters analysed, we recommend HPI
      assisted drying process at 350 MPa * 5 min as the best process condition to dry
      abalone. Variations in nutritional parameters compared to casein protein were
      observed; nevertheless, the high protein quality and digestibility of HPI
      assisted dried abalones were maintained to satisfy the metabolic demands of human
      beings.

PMID- 29051672
TI  - Photoinduced Organocatalyzed Atom Transfer Radical Polymerization Using
      Continuous Flow.
AB  - Organocatalyzed atom transfer radical polymerization (O-ATRP) has emerged as a
      metal-free variant of historically transition-metal reliant atom transfer radical
      polymerization. Strongly reducing organic photoredox catalysts have proven
      capable of mediating O-ATRP. To date, operation of photoinduced O-ATRP has been
      demonstrated in batch reactions. However, continuous flow approaches can provide
      efficient irradiation reaction conditions and thus enable increased
      polymerization performance. Herein, the adaptation of O-ATRP to a continuous flow
      approach has been performed with multiple visible-light absorbing photoredox
      catalysts. Using continuous flow conditions, improved polymerization results were
      achieved, consisting of narrow molecular weight distributions as low as 1.05 and
      quantitative initiator efficiencies. This system demonstrated success with 0.01%
      photocatalyst loadings and a diverse methacrylate monomer scope. Additionally,
      successful chain-extension polymerizations using 0.01 mol % photocatalyst
      loadings reveal continuous flow O-ATRP to be a robust and versatile method of
      polymerization.

PMID- 29051673
TI  - Local tidal regime dictates plasticity of expression of locomotor activity
      rhythms of American horseshoe crabs, Limulus polyphemus.
AB  - While horseshoe crabs Limulus polyphemus from regions with two daily tides
      express endogenous circatidal (~ 12.4 h) activity rhythms, much less is known
      about locomotor rhythm expression in horseshoe crabs from other tidal regimes.
      This study investigated whether horseshoe crabs (1) always express activity
      rhythms consistent with their natural tides, and (2) can alter activity rhythm
      expression in response to novel tide cycles. Activity rhythms of animals from
      environments with two daily tides (Gulf of Maine, 43 degrees 6' N/70 degrees 52'
      W, and Massachusetts, 41 degrees 32' N/70 degrees 40'W), one dominant daily tide
      (Apalachee Bay, Florida, 29 degrees 58' N/84 degrees 20' W), and microtides
      (Indian River Lagoon, Florida, 28 degrees 5' N/80 degrees 35' W) were recorded in
      2011-2013 during three artificial tide conditions: no tides, a 12.4 h tidal
      cycle, and a 24.8 h tidal cycle. Interestingly, L. polyphemus from the microtidal
      site (n = 7) appeared "plastic" in their responses; they were able to express
      both bimodal and unimodal rhythms in response to different tide cycles. In
      contrast, the other two populations exhibited more fixed responses: regardless of
      the tides they were exposed to, animals from areas with one dominant daily tide
      (n = 18) consistently expressed unimodal rhythms, while those from areas with two
      daily tides (n = 28) generally expressed bimodal rhythms. Rhythms expressed by L.
      polyphemus thus appear to be a function of endogenous clocks, the tidal cues to
      which animals are exposed, and tidal cues that animals experience throughout
      ontogeny.

PMID- 29051674
TI  - Mediterranean Diet and Prevention of Chronic Diseases.
AB  - A large body of research data suggests that traditional dietary habits and
      lifestyle unique to the Mediterranean region (Mediterranean diet, MD) lower the
      incidence of chronic diseases and improve longevity. These data contrast with
      troubling statistics in the United States and other high income countries
      pointing to an increase in the incidence of chronic diseases and the projected
      explosion in cost of medical care associated with an aging population. In 2013,
      the MD was inscribed by UNESCO in the "Representative List of the Intangible
      Cultural Heritage of Humanity." The 2015-2020 Dietary Guidelines for Americans
      included the MD as a healthy dietary pattern. Therefore, specific objectives of
      this article are to provide an overview of the nutritional basis of this
      healthful diet, its metabolic benefits, and its role in multiple aspects of
      disease prevention and healthy aging. Whereas recommendations about the MD often
      focus on specific foods or bioactive compounds, we suggest that the eating
      pattern as a whole likely contributes to the health promoting effects of the MD.

PMID- 29051675
TI  - Nickel-Catalyzed C-H Arylation of Benzoxazoles and Oxazoles: Benchmarking the
      Influence of Electronic, Steric and Leaving Group Variations in Phenolic
      Electrophiles.

PMID- 29051676
TI  - The Carrot and the Stick: A Cross-Sectional Study of the Influences on
      Responsible Merchant Practices to Reduce Underage Drinking.
AB  - Alcohol merchants (N=331) completed a cross-sectional survey assessing their
      attitudes and beliefs about underage drinking, its likely consequences,
      requirements for responsible beverage service (RBS) training, and performance of
      RBS practices and checking IDs. Merchants requiring more rigorous RBS training
      (i.e., state-approved versus in-house or none) have stronger beliefs that outlets
      who sell to minors will get cited and that their employees know RBS practices.
      Also, merchants who engage in more RBS practices require more rigorous RBS
      training, and believe more strongly that outlets who sell to minors are more
      likely to face, and deserve, stricter sanctions. Merchants who check IDs more
      strictly conduct more RBS practices and believe more strongly that underage
      drinking is serious and will result in stronger consequences if caught selling to
      minors. These findings about the attitudes, practices, and enforcement of alcohol
      merchants suggests ways communities can better target their limited resources to
      prevent underage drinking.

PMID- 29051677
TI  - The Treatment of Constipation-Predominant Irritable Bowel Syndrome with
      Acupuncture and Moxibustion: A Case Report.
AB  - Irritable bowel syndrome (IBS) is one of the most common functional
      gastrointestinal disorders in North America. The severity and chronic nature of
      this condition have a significant impact on health-related quality of life. With
      few effective therapies available, there is a need for integrative approaches to
      symptom management. This report describes a successful case of using acupuncture
      and moxibustion to reduce symptoms of constipation-predominant IBS.

PMID- 29051678
TI  - Rapid B-rep model preprocessing for immersogeometric analysis using analytic
      surfaces.
AB  - Computational fluid dynamics (CFD) simulations of flow over complex objects have
      been performed traditionally using fluid-domain meshes that conform to the shape
      of the object. However, creating shape conforming meshes for complicated
      geometries like automobiles require extensive geometry preprocessing. This
      process is usually tedious and requires modifying the geometry, including
      specialized operations such as defeaturing and filling of small gaps. Hsu et al.
      (2016) developed a novel immersogeometric fluid-flow method that does not require
      the generation of a boundary-fitted mesh for the fluid domain. However, their
      method used the NURBS parameterization of the surfaces for generating the surface
      quadrature points to enforce the boundary conditions, which required the B-rep
      model to be converted completely to NURBS before analysis can be performed. This
      conversion usually leads to poorly parameterized NURBS surfaces and can lead to
      poorly trimmed or missing surface features. In addition, converting simple
      geometries such as cylinders to NURBS imposes a performance penalty since these
      geometries have to be dealt with as rational splines. As a result, the geometry
      has to be inspected again after conversion to ensure analysis compatibility and
      can increase the computational cost. In this work, we have extended the
      immersogeometric method to generate surface quadrature points directly using
      analytic surfaces. We have developed quadrature rules for all four kinds of
      analytic surfaces: planes, cones, spheres, and toroids. We have also developed
      methods for performing adaptive quadrature on trimmed analytic surfaces. Since
      analytic surfaces have frequently been used for constructing solid models, this
      method is also faster to generate quadrature points on real-world geometries than
      using only NURBS surfaces. To assess the accuracy of the proposed method, we
      perform simulations of a benchmark problem of flow over a torpedo shape made of
      analytic surfaces and compare those to immersogeometric simulations of the same
      model with NURBS surfaces. We also compare the results of our immersogeometric
      method with those obtained using boundary-fitted CFD of a tessellated torpedo
      shape, and quantities of interest such as drag coefficient are in good agreement.
      Finally, we demonstrate the effectiveness of our immersogeometric method for high
      fidelity industrial scale simulations by performing an aerodynamic analysis of a
      truck that has a large percentage of analytic surfaces. Using analytic surfaces
      over NURBS avoids unnecessary surface type conversion and significantly reduces
      model-preprocessing time, while providing the same accuracy for the aerodynamic
      quantities of interest.

PMID- 29051679
TI  - Multivariate functional response regression, with application to fluorescence
      spectroscopy in a cervical pre-cancer study.
AB  - Many scientific studies measure different types of high-dimensional signals or
      images from the same subject, producing multivariate functional data. These
      functional measurements carry different types of information about the scientific
      process, and a joint analysis that integrates information across them may provide
      new insights into the underlying mechanism for the phenomenon under study.
      Motivated by fluorescence spectroscopy data in a cervical pre-cancer study, a
      multivariate functional response regression model is proposed, which treats
      multivariate functional observations as responses and a common set of covariates
      as predictors. This novel modeling framework simultaneously accounts for
      correlations between functional variables and potential multi-level structures in
      data that are induced by experimental design. The model is fitted by performing a
      two-stage linear transformation-a basis expansion to each functional variable
      followed by principal component analysis for the concatenated basis coefficients.
      This transformation effectively reduces the intra-and inter-function correlations
      and facilitates fast and convenient calculation. A fully Bayesian approach is
      adopted to sample the model parameters in the transformed space, and posterior
      inference is performed after inverse-transforming the regression coefficients
      back to the original data domain. The proposed approach produces functional tests
      that flag local regions on the functional effects, while controlling the overall
      experiment-wise error rate or false discovery rate. It also enables functional
      discriminant analysis through posterior predictive calculation. Analysis of the
      fluorescence spectroscopy data reveals local regions with differential
      expressions across the pre-cancer and normal samples. These regions may serve as
      biomarkers for prognosis and disease assessment.

PMID- 29051680
TI  - LIVING WITH PARENTS AND EMERGING ADULTS' DEPRESSIVE SYMPTOMS.
AB  - Whether moving back home after a period of economic independence, or having never
      moved out, the share of emerging adults living with parents is increasing. Yet
      little is known about the associations of coresidence patterns and rationales for
      coresidence for emerging adult well-being. Using the Toledo Adolescent
      Relationships Study (n = 891), we analyzed depressive symptoms among emerging
      adults who (1) never left the parental home; (2) returned to the parental home;
      and (3) were not currently living with a parent. About one-fifth of emerging
      adults had boomeranged or moved back in with their parents. Among those living
      with parents, nearly two-fifths had boomeranged or returned to their parental
      home and they reported significantly higher levels of depressive symptoms. Among
      coresident emerging adults, both intrinsic and utilitarian motivations (i.e.,
      enjoy living with parents and employment problems) partially mediated the
      association between coresidence and depressive symptoms. Returning to the
      parental home was associated with higher levels of depressive symptoms only among
      emerging adults experiencing employment problems. These findings are especially
      relevant because the recession hit emerging adults particularly hard. The ability
      to distinguish boomerang emerging adults and emerging adults who have never left
      home provides a more nuanced understanding of parental coresidence during this
      phase of the life course.

PMID- 29051682
TI  - Rapid recovery from aphasia after infarction of Wernicke's area.
AB  - BACKGROUND: Aphasia following infarction of Wernicke's area typically resolves to
      some extent over time. The nature of this recovery process and its time course
      have not been characterized in detail, especially in the acute/subacute period.
      AIMS: The goal of this study was to document recovery after infarction of
      Wernicke's area in detail in the first 3 months after stroke. Specifically, we
      aimed to address two questions about language recovery. First, which impaired
      language domains improve over time, and which do not? Second, what is the time
      course of recovery? METHODS & PROCEDURES: We used quantitative analysis of
      connected speech and a brief aphasia battery to document language recovery in two
      individuals with aphasia following infarction of the posterior superior temporal
      gyrus. Speech samples were acquired daily between 2 and 16 days post stroke, and
      also at 1 month and 3 months. Speech samples were transcribed and coded using the
      CHAT system, in order to quantify multiple language domains. A brief aphasia
      battery was also administered at a subset of five time points during the 3
      months. OUTCOMES & RESULTS: Both patients showed substantial recovery of language
      function over this time period. Most, but not all, language domains showed
      improvements, including fluency, lexical access, phonological retrieval and
      encoding, and syntactic complexity. The time course of recovery was logarithmic,
      with the greatest gains taking place early in the course of recovery.
      CONCLUSIONS: There is considerable potential for amelioration of language
      deficits when damage is relatively circumscribed to the posterior superior
      temporal gyrus. Quantitative analysis of connected speech samples proved to be an
      effective, albeit time-consuming, approach to tracking day-by-day recovery in the
      acute/subacute post-stroke period.

PMID- 29051681
TI  - A framelet-based iterative maximum-likelihood reconstruction algorithm for
      spectral CT.
AB  - Standard computed tomography (CT) cannot reproduce spectral information of an
      object. Hardware solutions include dual-energy CT which scans the object twice in
      different x-ray energy levels, and energy-discriminative detectors which can
      separate lower and higher energy levels from a single x-ray scan. In this paper,
      we propose a software solution and give an iterative algorithm that reconstructs
      an image with spectral information from just one scan with a standard energy
      integrating detector. The spectral information obtained can be used to produce
      color CT images, spectral curves of the attenuation coefficient MU(r, E)at points
      inside the object, and photoelectric images, which are all valuable imaging tools
      in cancerous diagnosis. Our software solution requires no change on hardware of a
      CT machine. With the Shepp-Logan phantom, we have found that although the
      photoelectric and Compton components were not perfectly reconstructed, their
      composite effect was very accurately reconstructed as compared to the ground
      truth and the dual-energy CT counterpart. This means that our proposed method has
      an intrinsic benefit in beam hardening correction and metal artifact reduction.
      The algorithm is based on a nonlinear polychromatic acquisition model for x-ray
      CT. The key technique is a sparse representation of iterations in a framelet
      system. Convergence of the algorithm is studied. This is believed to be the first
      application of framelet imaging tools to a nonlinear inverse problem.

PMID- 29051683
TI  - Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in
      Complex with CTX-M beta-Lactamase.
AB  - A series of six novel metallocenyl-7-ADCA (metallocenyl = ferrocenyl or
      ruthenocenyl; 7-ADCA = 7-aminodesacetoxycephalosporanic acid) conjugates were
      synthesized and their antibacterial properties evaluated by biochemical and
      microbiological assays. The ruthenocene derivatives showed a higher level of
      inhibition of DD-carboxypeptidase 64-575, a Penicillin Binding Protein (PBP),
      than the ferrocene derivatives and the reference compound penicillin G. Protein X
      ray crystallographic analysis revealed a covalent acyl-enzyme complex of a
      ruthenocenyl compound with CTX-M beta-lactamase E166A mutant, corresponding to a
      similar complex with PBPs responsible for the bactericidal activities of these
      compounds. Most interestingly, an intact compound was captured at the crystal
      packing interface, elucidating for the first time the structure of a metallocenyl
      beta-lactam compound that previously eluded small molecule crystallography. We
      propose that protein crystals, even from biologically unrelated molecules, can be
      utilized to determine structures of small molecules.

PMID- 29051685
TI  - Perceiving and Confronting Sexism: The Causal Role of Gender Identity Salience.
AB  - Although many researchers have explored the relations among gender
      identification, discriminatory attributions, and intentions to challenge
      discrimination, few have examined the causal impact of gender identity salience
      on women's actual responses to a sexist encounter. In the current study, we
      addressed this question by experimentally manipulating the salience of gender
      identity and assessing its impact on women's decision to confront a sexist
      comment in a simulated online interaction. Female participants (N = 114) were
      randomly assigned to complete a short measure of either personal or collective
      self-esteem, which was designed to increase the salience of personal versus
      gender identity. They were then given the opportunity to confront a male
      interaction partner who expressed sexist views. Compared to those who were primed
      to focus on their personal identity, participants who were primed to focus on
      their gender identity perceived the interaction partner's remarks as more sexist
      and were more likely to engage in confrontation. By highlighting the powerful
      role of subtle contextual cues in shaping women's perceptions of, and responses
      to, sexism, our findings have important implications for the understanding of
      gender identity salience as an antecedent of prejudice confrontation. Online
      slides for instructors who want to use this article for teaching are available on
      PWQ's website at http://journals.sagepub.com/page/pwq/suppl/index.

PMID- 29051684
TI  - A tripartite taxonomy of character: Evidence for intrapersonal, interpersonal,
      and intellectual competencies in children.
AB  - Other than cognitive ability, what competencies should schools promote in
      children? How are they organized, and to what extent do they predict
      consequential outcomes? Separate theoretical traditions have suggested
      interpersonal, intrapersonal, and intellectual dimensions, reflecting how
      children relate to other people, manage their own goals and impulses, and engage
      with ideas, respectively. However, very little work has examined character
      empirically. In the current investigation, we partnered with middle schools that
      had previously identified character strengths relevant in their communities.
      Across three longitudinal, prospective studies, we examined the factor structure
      of character, associations with intelligence and Big Five personality traits, and
      predictive validity for consequential outcomes like peer relations, class
      participation, and report card grades. In Study 1, teachers rated their students
      on behaviors exemplifying character strengths as they played out in students'
      daily lives. Exploratory factor analyses yielded a three-factor structure
      consisting of interpersonal (interpersonal self-control, gratitude, social
      intelligence), intellectual (zest, curiosity), and intrapersonal (academic self
      control, grit) factors of character. In Study 2, children rated their own
      behavior and completed a test of cognitive ability. Confirmatory factor analyses
      supported the same three-factor structure, and these factors were only weakly
      associated with cognitive ability. In Study 3, teachers provided character
      ratings; in parallel, students completed measures of character as well as Big
      Five personality factors. As expected, intellectual, interpersonal, and
      intrapersonal character factors related to Big Five openness to experience,
      agreeableness, and conscientiousness, respectively. Across studies, positive peer
      relations were most consistently predicted by interpersonal character, class
      participation by intellectual character, and report card grades by intrapersonal
      character. Collectively, our findings support a tripartite taxonomy of character
      in the school context.

PMID- 29051686
TI  - THE ROLE OF THE ASYMMETRIC BOLAAMPHIPHILIC CHARACTER OF VECAR ON THE KINETIC AND
      STRUCTURAL ASPECTS OF ITS SELF-ASSEMBLY: A MOLECULAR DYNAMICS SIMULATION STUDY.
AB  - VECAR are novel bolaamphiphilic molecules consisting of two hydrophilic molecular
      groups, a carnosine derivative and a chromanol group, covalently linked by a
      hydrophobic alkyl spacer of varying length. Despite the potential for application
      in various biomedical applications VECAR properties, including their bulk
      properties, are still largely unknown. The early stage of the self-assembly
      process of VECAR molecules in water is studied using molecular dynamics
      simulations. The study reveals that the length of the hydrophobic spacer in VECAR
      affects the aggregation kinetics as well as the size, shape, density, and
      atomistic structure of the self-assembled aggregates. A mechanism based on
      cooperative interactions between water, the hydrophilic hydroxyl group, and the
      hydrophobic benzene ring of the chromanol head is proposed to explain the ordered
      packings of chromanols in the self-assembled aggregate structures at the
      aggregate-water interface.

PMID- 29051687
TI  - Gadolinium-Loaded Viral Capsids as Magnetic Resonance Imaging Contrast Agents.
AB  - Polymeric nanohybrid P22 virus capsids were used as templates for high density
      Gd3+ loading to explore magnetic field-dependent (0.5-7.0 T) proton relaxivity.
      The field-dependence of relaxivity by the spatially constrained Gd3+ in the
      capsids was similar when either the loading of the capsids or the concentration
      of capsids was varied. The ionic longitudinal relaxivity, r1, decreased from 25
      32 mM-1 s-1 at 0.5 T to 6-10 mM-1 s-1 at 7 T. The ionic transverse relaxivity,
      r2, increased from 28-37 mM-1 s-1 at 0.5 T to 39-50 mM-1 s-1 at 7 T. The r2/r1
      ratio increased linearly with increasing magnetic field from about 1 at 0.5 T,
      which is typical of T1 contrast agents, to 5-8 at 7 T, which is approaching the
      ratios for T2 contrast agents. Increases in electron paramagnetic resonance line
      widths at 80 and 150 K and higher microwave powers required for signal saturation
      indicate enhanced Gd3+ electron spin relaxation rates for the Gd3+-loaded capsids
      than for low concentration Gd3+. The largest r2/r1 at 7 T was for the highest
      cage loading, which suggests that Gd3+-Gd3+ interactions within the capsid
      enhance r2 more than r1.

PMID- 29051688
TI  - Facilitating motor imagery-based brain-computer interface for stroke patients
      using passive movement.
AB  - Motor imagery-based brain-computer interface (MI-BCI) has been proposed as a
      rehabilitation tool to facilitate motor recovery in stroke. However, the
      calibration of a BCI system is a time-consuming and fatiguing process for stroke
      patients, which leaves reduced time for actual therapeutic interaction. Studies
      have shown that passive movement (PM) (i.e., the execution of a movement by an
      external agency without any voluntary motions) and motor imagery (MI) (i.e., the
      mental rehearsal of a movement without any activation of the muscles) induce
      similar EEG patterns over the motor cortex. Since performing PM is less fatiguing
      for the patients, this paper investigates the effectiveness of calibrating MI
      BCIs from PM for stroke subjects in terms of classification accuracy. For this
      purpose, a new adaptive algorithm called filter bank data space adaptation (FB
      DSA) is proposed. The FB-DSA algorithm linearly transforms the band-pass-filtered
      MI data such that the distribution difference between the MI and PM data is
      minimized. The effectiveness of the proposed algorithm is evaluated by an offline
      study on data collected from 16 healthy subjects and 6 stroke patients. The
      results show that the proposed FB-DSA algorithm significantly improved the
      classification accuracies of the PM and MI calibrated models (p < 0.05).
      According to the obtained classification accuracies, the PM calibrated models
      that were adapted using the proposed FB-DSA algorithm outperformed the MI
      calibrated models by an average of 2.3 and 4.5 % for the healthy and stroke
      subjects respectively. In addition, our results suggest that the disparity
      between MI and PM could be stronger in the stroke patients compared to the
      healthy subjects, and there would be thus an increased need to use the proposed
      FB-DSA algorithm in BCI-based stroke rehabilitation calibrated from PM.

PMID- 29051689
TI  - Detection of newly defined superantigenic toxin genes and coagulase gene
      polymorphism in Staphylococcus aureus isolates.
AB  - The current study aims to use coagulase (coa) polymorphism gene to identify
      Staphylococcus aureus isolated from stool samples, evaluate the efficiency of
      these methods in discriminating variable strains, and compare these subtypes with
      antibiotypes. A total of 100 specimens were collected from patients in Babylon
      province, Iraq, between July 2016 and September 2016. Twenty S. aureus strains
      were isolated and identified using standard laboratory microbiological tests. The
      bacterial isolates were then examined by coa gene restriction fragment length
      polymorphism genotyping. Out of 20 isolates, coa gene types were classified, and
      the amplification products showed multiple size bands (500, 600, 700, 800, and
      900-bp bands). Coa gene PCR restriction fragment length polymorphisms exhibited
      seven patterns that ranged from one to four fragments with AluI digestion. The
      results have demonstrated that many variants of the coa gene are present. At
      least one type of S. aureus newly described enterotoxin gene (staphylococcal
      enterotoxins) was harboring in all 20 (100%) of the isolates. The most frequently
      encountered gene were sei (100.%), seh (5%), seg (65%). Many S. aureus isolates
      carry at least one of the enterotoxin genes, and (95%) strains harbored more than
      one toxin gene coding.

PMID- 29051690
TI  - Better together: Simultaneous presentation of speech and gesture in math
      instruction supports generalization and retention.
AB  - When teachers gesture during instruction, children retain and generalize what
      they are taught (Goldin-Meadow, 2014). But why does gesture have such a powerful
      effect on learning? Previous research shows that children learn most from a math
      lesson when teachers present one problem-solving strategy in speech while
      simultaneously presenting a different, but complementary, strategy in gesture
      (Singer & Goldin-Meadow, 2005). One possibility is that gesture is powerful in
      this context because it presents information simultaneously with speech.
      Alternatively, gesture may be effective simply because it involves the body, in
      which case the timing of information presented in speech and gesture may be less
      important for learning. Here we find evidence for the importance of simultaneity:
      3rd grade children retain and generalize what they learn from a math lesson
      better when given instruction containing simultaneous speech and gesture than
      when given instruction containing sequential speech and gesture. Interpreting
      these results in the context of theories of multimodal learning, we find that
      gesture capitalizes on its synchrony with speech to promote learning that lasts
      and can be generalized.

PMID- 29051691
TI  - Quantitative-Voronovskaya and Gruss-Voronovskaya type theorems for Szasz
      Durrmeyer type operators blended with multiple Appell polynomials.
AB  - In this paper, we establish a link between the Szasz-Durrmeyer type operators and
      multiple Appell polynomials. We study a quantitative-Voronovskaya type theorem in
      terms of weighted modulus of smoothness using sixth order central moment and
      Gruss-Voronovskaya type theorem. We also establish a local approximation theorem
      by means of the Steklov means in terms of the first and the second order modulus
      of continuity and Voronovskaya type asymtotic theorem. Further, we discuss the
      degree of approximation by means of the weighted spaces. Lastly, we find the rate
      of approximation of functions having a derivative of bounded variation.

PMID- 29051692
TI  - New time scale generalizations of the Ostrowski-Gruss type inequality for k
      points.
AB  - Two Ostrowski-Gruss type inequalities for k points with a parameter [Formula: see
      text] are hereby presented. The first generalizes a recent result due to Nwaeze
      and Tameru, and the second extends the result of Liu et al. to k points. Many new
      interesting inequalities can be derived as special cases of our results by
      considering different values of lambda and [Formula: see text]. In addition, we
      apply our results to the continuous, discrete, and quantum time scales to obtain
      several novel inequalities in this direction.

PMID- 29051693
TI  - [Formula: see text]-statistical convergence of order alpha for double sequences.
AB  - New concepts of [Formula: see text]-statistical convergence for double sequences
      of order alpha and strong [Formula: see text]-Cesaro summability for double
      sequences of order alpha are introduced for sequences of (complex or real)
      numbers. Furthermore, we give the relationship between the spaces [Formula: see
      text], [Formula: see text] and [Formula: see text]. Then we express the
      properties of strong [Formula: see text]-Cesaro summability of order beta which
      is related to strong [Formula: see text]-Cesaro summability of order alpha. Also,
      some relations between [Formula: see text]-statistical convergence of order alpha
      and strong [Formula: see text]-Cesaro summability of order alpha are given.

PMID- 29051694
TI  - Implicit and explicit iterative algorithms for hierarchical variational
      inequality in uniformly smooth Banach spaces.
AB  - The purpose of this paper is to solve the hierarchical variational inequality
      with the constraint of a general system of variational inequalities in a
      uniformly convex and 2-uniformly smooth Banach space. We introduce implicit and
      explicit iterative algorithms which converge strongly to a unique solution of the
      hierarchical variational inequality problem. Our results improve and extend the
      corresponding results announced by some authors.

PMID- 29051695
TI  - G2 continuity conditions for generalized Bezier-like surfaces with multiple shape
      parameters.
AB  - In order to tackle the problem of shape design and shape adjustment of complex
      surfaces in engineering, continuity conditions between generalized Bezier-like
      surfaces with multiple shape parameters are studied in this paper. Firstly, the
      geometric model of the generalized Bezier-like surfaces is built by blending a
      number of Bezier-like curves with independent shape parameters. Secondly, based
      on the terminal properties and linear independence of Bernstein-like basis
      functions, the conditions for G2 continuity between two adjacent generalized
      Bezier-like surfaces are derived, and then simplified by choosing appropriate
      shape parameters. Finally, some properties and applications of the smooth
      continuity between generalized Bezier-like surfaces are discussed. The modeling
      examples show that the proposed method is effective and easy to implement, which
      can greatly improve the ability to construct complex surfaces by using the
      generalized Bezier-like surfaces.

PMID- 29051696
TI  - Relatedness-based Multi-Entity Summarization.
AB  - Representing world knowledge in a machine processable format is important as
      entities and their descriptions have fueled tremendous growth in knowledge-rich
      information processing platforms, services, and systems. Prominent applications
      of knowledge graphs include search engines (e.g., Google Search and Microsoft
      Bing), email clients (e.g., Gmail), and intelligent personal assistants (e.g.,
      Google Now, Amazon Echo, and Apple's Siri). In this paper, we present an approach
      that can summarize facts about a collection of entities by analyzing their
      relatedness in preference to summarizing each entity in isolation. Specifically,
      we generate informative entity summaries by selecting: (i) inter-entity facts
      that are similar and (ii) intra-entity facts that are important and diverse. We
      employ a constrained knapsack problem solving approach to efficiently compute
      entity summaries. We perform both qualitative and quantitative experiments and
      demonstrate that our approach yields promising results compared to two other
      stand-alone state-of-the-art entity summarization approaches.

PMID- 29051698
TI  - Data Citation: a Computational Challenge.
AB  - Data citation is an interesting computational challenge, whose solution draws on
      several well-studied problems in database theory: query answering using views,
      and provenance. We describe the problem, suggest an approach to its solution, and
      highlight several open research problems, both practical and theoretical.

PMID- 29051697
TI  - New fluphenazine analogue with antimutagenic and anti-multidrug resistance
      activity-degradation profile and stability-indicating method.
AB  - Hydrochloride of 10-{2-hydroxy-3-[N,N-bis-(2-hydroxyethyl)amino]propyl}-2
      trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine.
      Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer
      chemopreventive activities in screening studies. To define identity, quality, and
      purity of new active substance it is necessary to develop a appropriate
      analytical method and to establish a degradation profile. Thus, a stability
      indicating reversed-phase high-performance liquid chromatography method was
      developed and validated for quantitative determination of Flu-A in the presence
      of its degradation products generated under stress conditions. The compound was
      subjected to oxidation, photolysis, and degradation in aqueous solutions (neutral
      and acidic), and solid state according to the International Council for
      Harmonisation Guidelines. The method was also found to be suitable for
      intermediate and accelerated studies and for the evaluation of kinetic mechanism
      of Flu-A degradation in aqueous solutions (pH 5.1-7.5, 353 K). The structures of
      main potential degradation products were established using high-performance
      liquid chromatography-Electrospray Ionization-mass spectrometry method.

PMID- 29051699
TI  - Parental Divorce, Familial Risk for Depression, and Psychopathology in Offspring:
      A Three-Generation Study.
AB  - Research suggests a link between parental divorce and negative child outcomes;
      however, the presence of parental depression may confound this relationship.
      Studies exploring the simultaneous effects of depression and parents' divorce on
      the adjustment of their children are scarce and rarely have a longitudinal
      design. This is the first three-generation study of the relative effects of
      depression and divorce on offspring psychopathology, based on data from a 25-year
      longitudinal study with families at high and low risk for depression. One hundred
      seventy-eight grandchildren (mean age = 13.9 years) of depressed and nondepressed
      parents and grandparents were evaluated by raters blind to their parents' and
      grandparents' clinical status. We found that in both low and high-risk children,
      divorce had a limited impact on child adjustment over and above familial risk for
      depression. Divorce had a significant effect on child outcomes only among high
      risk grandchildren with a depressed grandparent and non-depressed parents, with
      this group showing a threefold risk for anxiety disorders. Results support
      previous findings suggesting that familial risk for depression largely
      overshadows the effect of parental divorce on child psychopathology. Possible
      reasons for the lack of association between divorce and child psychopathology
      among low-risk offspring are discussed.

PMID- 29051700
TI  - Adolescent Sex Differences in Response to a Mindfulness Intervention: A Call for
      Research.
AB  - Research on mindfulness interventions with adolescents has burgeoned over the
      last ten years, and findings have demonstrated increases in overall emotional
      wellbeing post-intervention. However, little is known about the differences
      between males and females in response to mindfulness interventions in this age
      group. In the present study we examine sex differences in outcomes of
      physiological stress markers during the Trier Social Stress Test (TSST) and
      emotional wellbeing measures before and after a mindfulness intervention (N = 15)
      with 10 female and 5 male adolescents. Additionally, we examine sex differences
      in course engagement and post-intervention use of mindfulness skills during the
      TSST. Overall, we found some evidence that females were more engaged than males
      in the class and also reported less stress post-intervention. We conclude by
      strongly encouraging future research in this area to more clearly elucidate the
      different ways in which adolescent males and females engage and respond to
      mindfulness interventions.

PMID- 29051701
TI  - MGUPGMA: A Fast UPGMA Algorithm With Multiple Graphics Processing Units Using
      NCCL.
AB  - A phylogenetic tree is a visual diagram of the relationship between a set of
      biological species. The scientists usually use it to analyze many characteristics
      of the species. The distance-matrix methods, such as Unweighted Pair Group Method
      with Arithmetic Mean and Neighbor Joining, construct a phylogenetic tree by
      calculating pairwise genetic distances between taxa. These methods have the
      computational performance issue. Although several new methods with high
      performance hardware and frameworks have been proposed, the issue still exists.
      In this work, a novel parallel Unweighted Pair Group Method with Arithmetic Mean
      approach on multiple Graphics Processing Units is proposed to construct a
      phylogenetic tree from extremely large set of sequences. The experimental results
      present that the proposed approach on a DGX-1 server with 8 NVIDIA P100 graphic
      cards achieves approximately 3-fold to 7-fold speedup over the implementation of
      Unweighted Pair Group Method with Arithmetic Mean on a modern CPU and a single
      GPU, respectively.

PMID- 29051702
TI  - Finding the Sources of Missing Heritability within Rare Variants Through
      Simulation.
AB  - Thousands of genome-wide association studies (GWAS) have been conducted to
      identify the genetic variants associated with complex disorders. However, only a
      small proportion of phenotypic variances can be explained by the reported
      variants. Moreover, many GWAS failed to identify genetic variants associated with
      disorders displaying hereditary features. The "missing heritability" problem can
      be partly explained by rare variants. We simulated a causality scenario that
      gestational ages, a quantitative trait that can distinguish preterm (<37 weeks)
      and term births, were significantly correlated with the rare variant aggregations
      at 1000 single-nucleotide polymorphism loci. These 1000 simulated causal rare
      variants were embedded into randomly selected subsets of 9642 promoter regions
      from the 1000 Genomes Project genotypic data according to different proportions
      of causal rare variants within the embedded promoters. Through analysis of the
      correlations between rare variant aggregations and gestational ages, we found
      that the embedded promoters as a whole showed weaker genetic association when the
      proportion of causal rare variants decreased, and no individual embedded
      promoters showed genetic association when the proportion of causal rare variants
      was smaller than 0.4. Our analyses indicate that association signals can be
      greatly diluted when causal rare variants are dispersedly and sparsely
      distributed in the genome, accounting for an important source of missing
      heritability.

PMID- 29051703
TI  - Buprenorphine/Naloxone Maintenance Therapy: an Observational Retrospective Report
      on the Effect of Dose on 18 months Retention in an Office-Based Treatment
      Program.
AB  - CONTEXT AND OBJECTIVE: Buprenorphine has been available with few reports of the
      dose range necessary to adequately maintain patients. We report on the effect of
      8 mg/d versus 16 mg/d of buprenorphine on long-term patient retention in office
      based opioid maintenance (OBOMT). DESIGN SETTING AND PARTICIPANTS: Case series,
      at an urban hospital-based primary care clinic providing OBOMT to 157 opiate
      dependent, low socioeconomic status, uninsured, nonhomeless patients.
      INTERVENTION: The OBOMT program operated by a comprehensive sobriety treatment
      program experienced State funding cuts. Thus, after 2 years, the program was
      required by the State funder to decrease the buprenorphine maintenance dose from
      16 to 8 mg/d for all new admissions. We report on patient retention before and
      after dose reduction. MAIN OUTCOME MEASURES: The primary outcomes of this study
      were to measure and compare patient retention in the 2 cohorts at each point of
      treatment transition over the 18 months following OBOMT initiation. RESULTS: No
      significant differences in patient retention were observed between the 16 and 8
      mg/d patient cohorts. Lower dose buprenorphine maintenance (8 mg/d) in uninsured
      patients enrolled in publicly funded long-term OBOMT combined with comprehensive
      sobriety counseling was as effective as higher dose therapy (16 mg/d) in
      promoting patient retention throughout the study period. This lower dose resulted
      in a substantial saving to the public funding agency. CONCLUSIONS: In an
      observational retrospective report, retention in treatment of opiate-addicted
      patients was the same at 8 and 16 mg/d buprenorphine doses after 18 months. These
      data have implications for public and managed care funding of OBOMT, for the
      general prescribing of buprenorphine in outpatient care, and may be instructive
      in the ongoing debate about the relationship between buprenorphine dose.

PMID- 29051704
TI  - Palliation Versus Dialysis for End-Stage Renal Disease in the Oldest Old: What
      are the Considerations?
AB  - As the US population continues to age, new cases of end-stage renal disease
      (ESRD) in individuals, aged 85 years or older (the oldest old), are increasing.
      Many patients who begin hemodialysis despite questionable benefit may struggle
      with high symptom burden and rapid functional decline. This article reviews the
      history regarding the funding and development of the Medicare ESRD program,
      reviews current approaches to the oldest old with ESRD, and considers strategies
      to improve the management approach of this vulnerable population.

PMID- 29051705
TI  - Open Defaecation and Its Effects on the Bacteriological Quality of Drinking Water
      Sources in Isiolo County, Kenya.
AB  - BACKGROUND INFORMATION: The post-2015 Sustainable Development Goals for
      sanitation call for universal access to adequate and equitable sanitation and an
      end to open defaecation by 2030. In Isiolo County, a semi-arid region lying in
      the northern part of Kenya, poor sanitation and water shortage remain a major
      problem facing the rural communities. OBJECTIVE: The overall aim of the study was
      to assess the relationship between sanitation practices and the bacteriological
      quality of drinking water sources. The study also assessed the risk factors
      contributing to open defaecation in the rural environments of the study area.
      METHODS: A cross-sectional study of 150 households was conducted to assess the
      faecal disposal practices in open defaecation free (ODF) and open defaecation not
      free (ODNF) areas. Sanitary surveys and bacteriological analyses were conducted
      for selected community water sources to identify faecal pollution sources,
      contamination pathways, and contributory factors. Analysis of data was performed
      using SPSS (descriptive and inferential statistics at alpha = .05 level of
      significance). RESULTS: Open defaecation habit was reported in 51% of the study
      households in ODNF villages and in 17% households in ODF villages. Higher mean
      colony counts were recorded for water samples from ODNF areas 2.0, 7.8, 5.3, and
      7.0 (*103) colony-forming units (CFUs)/100 mL compared with those of ODF 1.8,
      6.4, 3.5, and 6.1 (*103) areas for Escherichia coli, faecal streptococci,
      Salmonella typhi, and total coliform, respectively. Correlation tests revealed a
      significant relationship between sanitary surveys and contamination of water
      sources (P = .002). CONCLUSIONS: The water sources exhibited high levels of
      contamination with microbial pathogens attributed to poor sanitation. Practising
      safe faecal disposal in particular is recommended as this will considerably
      reverse the situation and thus lead to improved human health.

PMID- 29051706
TI  - Investigation of the Tissue Distribution and Physiological Roles of Indoleamine
      2,3-Dioxygenase-2.
AB  - Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the
      first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other
      enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a
      role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1)
      expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is
      reportedly expressed comparatively narrow, including in liver, kidney, brain, and
      in certain immune cell types, and it does not appear to contribute significantly
      to systemic tryptophan catabolism under normal physiological conditions. Here, we
      report the identification of an alternative splicing pattern, including the use
      of an alternative first exon, that is conserved in the mouse Ido1 and Ido2 genes.
      These findings prompted us to assess IDO2 protein expression and enzymatic
      activity in tissues. Our analysis, undertaken in Ido2 +/+ and Ido2-/- mice using
      immunohistochemistry and measurement of tryptophan and kynurenine levels,
      suggested an even more restricted pattern of tissue expression than previously
      reported. We found IDO2 protein to be expressed in the liver with a
      perinuclear/nuclear, rather than cytoplasmic, distribution. Consistent with
      earlier reports, we found Ido2 -/- mice to be phenotypically similar to their
      Ido2+/+ counterparts regarding levels of tryptophan and kynurenine in the plasma
      and liver. Our findings suggest a specialized function or regulatory role for
      IDO2 associated with its particular subcellular localization.

PMID- 29051708
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/1179551417710209.].

PMID- 29051707
TI  - Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth
      Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee
      Osteoarthritis: A Single-Blinded Randomized Clinical Trial.
AB  - BACKGROUND AND OBJECTIVES: Knee osteoarthritis is the most common joint disease.
      We aimed to compare the efficacy and safety of intra-articular injection of a
      newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA)
      on pain and function of patients with knee osteoarthritis. METHODS: In this
      single-blinded randomized clinical trial, patients with symptomatic
      osteoarthritis of knee were assigned to receive 2 intra-articular injections of
      our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary
      outcome was the mean change from baseline until 2 and 6 months post intervention
      in scores of visual analog scale, Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance
      for repeated-measures statistical test. RESULTS: A total of 69 patients entered
      final analysis. The mean age of patients was 58.2 +/- 7.41 years and 81.2% were
      women. In particular, total WOMAC index decreased from 42.9 +/- 13.51 to 26.8 +/-
      13.45 and 24.4 +/- 16.54 at 2 and 6 months in the newly developed PRGF group
      (within subjects P = .001), and from 38.8 +/- 12.62 to 27.8 +/- 11.01 and 27.4 +/
      11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively
      (between subjects P = .631). There was no significant difference between PRGF and
      HA groups in patients' satisfaction and minor complications of injection, whereas
      patients in HA group reported significantly lower injection-induced pain.
      CONCLUSIONS: In 6 months follow up, our newly developed PRGF and HA, both are
      effective options to decrease pain and improvement of function in patients with
      symptomatic mild to moderate knee osteoarthritis.

PMID- 29051710
TI  - Knowledge and care seeking practices for ear infections among parents of under
      five children in Kigali, Rwanda: a cross-sectional study.
AB  - BACKGROUND: Infections affecting the middle ear are a common childhood
      occurrence. Some cases may present with ear discharge through a tympanic membrane
      perforation which may heal spontaneously. However, up to 5% or more cases of
      those affected have persistent ear discharge. A number of barriers contribute
      towards delayed presentation at health facilities for treatment of ear
      infections. We conducted a study to evaluate parents' and caregivers' knowledge
      and care seeking practices for ear infections in children under five in Gasabo
      district in Kigali, Rwanda. METHODS: Parents/guardians (n = 810) were interviewed
      using a structured questionnaire to elicit their knowledge of ear infections in
      children under five and their attitude to seeking care for their children.
      RESULTS: The mean age of the respondents was 31.27 years (SD = 7.88, range 17
      83). Considering an average of knowledge parameters which included causes,
      symptoms, prevention, treatment and consequences of ear infections, we found that
      76.6% (622) of respondents were knowledgeable about ear infections. We defined a
      positive practice as seeking medical treatment (community health workers or
      health facility) and this was found in 89.1% (722) respondents. Correlating
      knowledge with choice of seeking treatment, respondents were 33% less likely to
      practice medical pluralism (OR = 0.33, CI 0.11-0.97, P = 0.043) if they were
      familiar with infections. Moreover, urban dweller were 1.7 times more likely to
      know ear infections compared to rural dwellers (OR = 1.70, CI 1.22-2.38, P =
      0.002). CONCLUSION: The majority of respondents had good knowledge and positive
      attitudes and practices about ear infection. However, medical pluralism was
      common. There is need to improve the community's awareness and access to primary
      health care facilities for the care of ear infections especially in rural areas
      of Rwanda.

PMID- 29051711
TI  - Down-regulation of IFITM1 and its growth inhibitory role in cervical squamous
      cell carcinoma.
AB  - BACKGROUND: Cervical cancer is a major cause of death in women worldwide.
      Interferon-induced transmembrane protein 1 (IFITM1) is involved in antivirus
      defense, cell adhesion, and carcinogenesis in different tissues. However, the
      role of IFITM1 gene in cervical squamous cell cancer is unclear. METHODS: To
      explore the role of IFITM1 in carcinogenesis of cervical cancer, we investigated
      the expression of IFITM1 gene in cervical squamous cell carcinoma. IFITM1 mRNA
      level was measured by real-time quantitative RT-PCR in cervical cancer tissues
      and their adjacent normal tissues. IFITM1 protein level was measured by
      immunohistochemistry. Methylation in the IFITM1 gene promoter was detected by
      methylation-specific PCR. We then transfected HeLa cells with IFITM1 expression
      vector or control vector. IFITM1 expression was examined; cell migration and
      invasion were analyzed by wound healing assay and matrigel-coated transwell
      migration assays, respectively. HeLa cell proliferation was measured by cell
      counting kit-8 assay and cell cycle analysis. Cell apoptosis was analyzed by
      Annexin V/propidium iodide double staining assay. RESULTS: The difference in
      IFITM1 protein expression between samples from chronic cervicitis and cervical
      carcinoma was statistically significant (P < 0.01). Ki-67 and PCNA protein
      expression levels were significantly higher in cervical cancer tissues than in
      their corresponding cervicitis tissues (P < 0.05 and P < 0.001, respectively).
      IFITM1 mRNA level was significantly lower in cervical cancer tissues than in
      normal cervical tissues (P < 0.05). Methylation of the IFITM1 gene promoter was
      significantly higher in cervical cancer than in normal cervical tissues (P <
      0.05). Transfection of the IFITM1 pcDNA3.1 construct decreased cell migration and
      invasion of HeLa cells, inhibited cell proliferation, and increased cell
      apoptosis. CONCLUSION: IFITM1 gene expression may reduce the proliferation,
      migration, and invasion of cervical squamous cancer cells.

PMID- 29051712
TI  - How can Developmental Systems Theories Cope with Free Will? The importance of
      stress-related growth and mindfulness.
AB  - Science is in the midst of a Kuhnian paradigm shift, from causal, deterministic
      models to more probabilistic ones that emphasize systems approaches. However,
      systems theory is still primarily deterministic and does not readily integrate
      the construct of free will. In the developmental sciences, this shift has been
      manifesting in relational developmental systems theories (RSDTs) which highlight
      multi-level analyses, interindividual differences in intraindividual change, and
      co-action with the context. While agency is an important component in RSDTs, it
      is unclear how it develops. We argue that free will is a developmental construct,
      and that the process of the development of free will can arise in two ways: from
      life-changing encounters with major stressors which result in recognizing
      limiting influences on one's life and the development of greater self-awareness;
      and purposive development to increase self-regulation and mindfulness. Through
      purposive, mindful co-action, the individual and the network can co-evolve in
      positive ways.

PMID- 29051713
TI  - What Is Electromotility? -The History of Its Discovery and Its Relevance to
      Acoustics.
AB  - Experiments on an inner ear sensory cell revealed that it converts electrical
      energy directly into mechanical energy at acoustic frequencies.

PMID- 29051709
TI  - Effect of Androgen Deprivation Therapy on Bone Mineral Density in a Prostate
      Cancer Cohort in New Zealand: A Pilot Study.
AB  - INTRODUCTION: Reduction in bone mineral density (BMD) is a common side effect of
      androgen deprivation therapy (ADT). We aimed to examine the cross-sectional and
      longitudinal variation in BMD and associated bone markers in patients with
      nonmetastatic prostate cancer (PCa) managed with and without ADT. METHODS: Bone
      mineral density of the total body, lumbar spine, femoral neck, ultradistal
      forearm, and one-third distal radius was measured in 88 patients with PCa without
      bone metastases at baseline and at 6 months. Patients were categorized into 4
      groups: (1) acute ADT (<=6 months), (2) chronic ADT (>6 months), (3) former ADT,
      and (4) no ADT (controls). Serum levels of bone metabolism markers, procollagen
      type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of
      type I collagen (CTX), were also measured. RESULTS: In the cross-sectional
      analysis, men receiving chronic ADT had significantly lower total body BMD as
      compared with former ADT users and men with no ADT. In longitudinal analysis, a
      significant reduction in ultradistal forearm BMD was observed in both acute and
      chronic ADT users after 6 months (4.08% and 2.7%, P = .012 and .026,
      respectively). A significant reduction in total body BMD was observed in acute
      ADT users (2.99%, P = .032). Former ADT users had a significant increase in both
      lumbar spine and femoral neck BMD (2.84% and 1.59%, P = .008 and .002,
      respectively). The changes in BMD were not significantly different between acute
      and chronic ADT users. In the cross-sectional analysis, higher levels of PINP and
      CTX were observed in acute and chronic ADT users than former ADT users or PCa
      controls. In longitudinal analysis, the level of serum PINP and CTX did not
      change significantly from baseline to 6 months in acute, chronic, and former ADT
      users, or PCa controls, and the percentage change did not differ among the 4
      groups. CONCLUSIONS: Men on acute ADT had a similar rate of bone loss to men on
      chronic ADT. Reversibility in ADT-induced bone loss was observed in those who
      discontinued ADT. Serum levels of PINP and CTX were higher in acute and chronic
      ADT users and levels returned to the range of PCa controls when treatment was
      withdrawn.

PMID- 29051714
TI  - A Self-Report Measure to Detect Neurocognitive Impairment among Incarcerated
      People Living with HIV in Malaysian Context: An Exploratory Factor Analysis.
AB  - While neurocognitive impairment (NCI) among people living with HIV (PLWH) who use
      drugs and its impact on HIV treatment outcomes continue to be widely
      investigated, there remains a critical gap in NCI assessment among HIV-infected
      people who use drugs (PWUD) in Malaysian context. The present study, therefore,
      sought to improve the utility of the existing Neuropsychological Impairment Scale
      (NIS) as a screening tool for assessing NCI by establishing its psychometric
      properties in the Malaysian context. The NIS is a brief, self-report measure
      originally designed to assess NCI by having individuals rate a range of items
      that may influence cognitive functioning. HIV-infected male prisoners (N=301)
      administered the full 95-item NIS. An exploratory factor analysis (EFA) was
      conducted using principal axis factoring and orthogonal varimax rotation.
      Reliability was measured using Cronbach's alpha. The EFA resulted in an
      abbreviated, psychometrically sound, eight-factor structure (54-item) revised NIS
      - now referred to as the Brief Inventory of Neuro-cognitive Impairment-Malaysia
      (BINI-M). It is better designed to detect NCI in PLWH, ranging from generalized
      neurocognitive symptoms to more specific forms of impairment with excellent to
      average reliability. The BINI-M may serve as a useful tool for clinicians and
      researchers to assess NCI in PLWH and can inform enhanced treatment strategies in
      the Malaysian context.

PMID- 29051716
TI  - Assessment of the Effects of Graded Doses of Polyphenolic-Rich Fraction of
      Garcinia kola Seeds on Pituitary-Testicular Axis of Male Wistar Rats.
AB  - This study evaluated the ameliorative and prophylactic effects of 2 different
      doses of polyphenolic-rich fraction of Garcinia kola (PPRFGk) seeds on the
      histology and hormones of pituitary-testicular axis of male Wistar rats. Thirty
      five male Wistar rats (150-200 g) were divided into 7 groups of 5 rats each.
      Groups I and II were given distilled water (0.5 mL/day) for 8 days followed by
      propylene glycol (0.2 mL/d) and 600 mg/kg of PPRFGk, respectively, for 21 days.
      Group III received sodium arsenate (8 days), left untreated for 21 days. Groups
      IV and V received sodium arsenate (20 mg/kg) for 8 days followed by PPRFGk (300
      and 600 mg/kg, respectively) for 21 days. Groups VI and VII received PPRFGk (300
      and 600 mg/kg, respectively) for 21 days followed by sodium arsenate (20 mg/kg)
      for 8 days. Rats were killed by cervical dislocation 24 hours after the last dose
      and their blood collected through cardiac puncture. Blood sera were assayed for
      the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and
      testosterone using immunoassay techniques. Histology of the pituitary gland and
      testes was carried out. A significant reduction was observed in the concentration
      of FSH in groups IV, V, VI, and VII in comparison with groups I and II. The
      concentrations of both LH and testosterone showed significant decreases in groups
      IV, V, VI, and VII in comparison with group I. Group III presented with the
      lowest serum hormonal concentrations. Photomicrographs of the pituitary gland
      revealed greatly reduced basophils in group III and mildly reduced basophils in
      groups IV, VI, and VII in comparison with groups I and II. Group V revealed
      hypercellularized and distorted basophils. Photomicrographs of the testes showed
      detachment of the seminiferous tubules from the basement membrane and disruption
      of the interstitial space which was worse in group III, moderate in groups V and
      VI, and mild in group VII. In conclusion, PPRFGk effected a dose-dependent
      reversal and prevention of the perturbations caused by arsenate in rats.

PMID- 29051715
TI  - A multiplex platform for the identification of ovarian cancer biomarkers.
AB  - BACKGROUND: Currently, there are no FDA approved screening tools for detecting
      early stage ovarian cancer in the general population. Development of a biomarker
      based assay for early detection would significantly improve the survival of
      ovarian cancer patients. METHODS: We used a multiplex approach to identify
      protein biomarkers for detecting early stage ovarian cancer. This new technology
      (Proseek(r) Multiplex Oncology Plates) can simultaneously measure the expression
      of 92 proteins in serum based on a proximity extension assay. We analyzed serum
      samples from 81 women representing healthy, benign pathology, early, and advanced
      stage serous ovarian cancer patients. RESULTS: Principle component analysis and
      unsupervised hierarchical clustering separated patients into cancer versus non
      cancer subgroups. Data from the Proseek(r) plate for CA125 levels exhibited a
      strong correlation with current clinical assays for CA125 (correlation
      coefficient of 0.89, 95% CI 0.83, 0.93). CA125 and HE4 were present at very low
      levels in healthy controls and benign cases, while higher levels were found in
      early stage cases, with highest levels found in the advanced stage cases.
      Overall, significant trends were observed for 38 of the 92 proteins (p < 0.001),
      many of which are novel candidate serum biomarkers for ovarian cancer. The area
      under the ROC curve (AUC) for CA125 was 0.98 and the AUC for HE4 was 0.85 when
      comparing early stage ovarian cancer versus healthy controls. In total, 23
      proteins had an estimated AUC of 0.7 or greater. Using a naive Bayes classifier
      that combined 12 proteins, we improved the sensitivity corresponding to 95%
      specificity from 93 to 95% when compared to CA125 alone. Although small, a 2%
      increase would have a significant effect on the number of women correctly
      identified when screening a large population. CONCLUSIONS: These data demonstrate
      that the Proseek(r) technology can replicate the results established by
      conventional clinical assays for known biomarkers, identify new candidate
      biomarkers, and improve the sensitivity and specificity of CA125 alone.
      Additional studies using a larger cohort of patients will allow for validation of
      these biomarkers and lead to the development of a screening tool for detecting
      early stage ovarian cancer in the general population.

PMID- 29051717
TI  - Continuous Low-Dose-Rate Irradiation Promotes Growth of Silkworms.
AB  - To investigate the influence of low-dose-rate irradiation on the growth of
      silkworms, Bombyx mori, eggs of silkworms were randomly divided into 2 groups and
      were grown on either low-dose-radiation-emitting sheets or control sheets. On the
      radiation-emitting sheets, the dose rate was measured as 66.0 (4.3) MUSv/h (mean
      [standard deviation]) by a Geiger-Muller counter for alpha, beta, and gamma rays
      and 3.8 (0.3) MUSv/h by a survey meter for gamma rays. The silkworms became
      larger when bred on the radiation-emitting sheets, and their body weight was
      about 25% to 37% heavier on day 42 to 49 after starting the experiment.
      Continuous low-dose-rate irradiation promoted the growth of silkworms. It should
      be further investigated whether this phenomenon could be utilized by the silk
      industry.

PMID- 29051718
TI  - The Mistaken Birth and Adoption of LNT: An Abridged Version.
AB  - The historical foundations of cancer risk assessment were based on the discovery
      of X-ray-induced gene mutations by Hermann J. Muller, its transformation into the
      linear nonthreshold (LNT) single-hit theory, the recommendation of the model by
      the US National Academy of Sciences, Biological Effects of Atomic Radiation I,
      Genetics Panel in 1956, and subsequent widespread adoption by regulatory agencies
      worldwide. This article summarizes substantial recent historical revelations of
      this history, which profoundly challenge the standard and widely acceptable
      history of cancer risk assessment, showing multiple significant scientific errors
      and incorrect interpretations, mixed with deliberate misrepresentation of the
      scientific record by leading ideologically motivated radiation geneticists. These
      novel historical findings demonstrate that the scientific foundations of the LNT
      single-hit model were seriously flawed and should not have been adopted for
      cancer risk assessment.

PMID- 29051719
TI  - Computational Population Biology: Linking the inner and outer worlds of
      organisms.
AB  - Computationally complex systems models are needed to advance research and
      implement policy in theoretical and applied population biology. Difference and
      differential equations used to build lumped dynamic models (LDMs) may have the
      advantage of clarity, but are limited in their inability to include fine-scale
      spatial information and individual-specific physical, physiological,
      immunological, neural and behavioral states. Current formulations of agent-based
      models (ABMs) are too idiosyncratic and freewheeling to provide a general,
      coherent framework for dynamically linking the inner and outer worlds of
      organisms. Here I propose principles for a general, modular, hierarchically
      scalable, framework for building computational population models (CPMs) designed
      to treat the inner world of individual agents as complex dynamical systems that
      take information from their spatially detailed outer worlds to drive the dynamic
      inner worlds of these agents, simulate their ecology and the evolutionary
      pathways of their progeny. All the modeling elements are in place, although
      improvements in software technology will be helpful; but most of all we need a
      cultural shift in the way population biologists communicate and share model
      components and the models themselves, fit, test, refute, and refine models, to
      make the progress needed to meet the ecosystems management challenges posed by
      global change biology.

PMID- 29051720
TI  - Old age pension and intergenerational living arrangements: a regression
      discontinuity design.
AB  - China launched a pension program for rural residents in 2009, now covering more
      than 300 million Chinese. This program offers a unique setting for studying the
      ageing population, given the rapidity of China's population ageing, traditions of
      filial piety and co-residence, decreasing number of children, and dearth of
      formal social security, at a relatively low income level. This paper examines
      whether receipt of the old-age pension payment equips elderly parents and their
      adult children to live apart and whether parents substitute children's time
      involved in instrumental support to them with service consumption. Employing a
      regression discontinuity design to a primary longitudinal survey conducted in
      Guizhou province of China, this paper overcomes challenges in the literature that
      households eligible for pension payment might be systematically different from
      ineligible households and that it is difficult to separate the effect of pension
      from that of age or cohort heterogeneity. Around the pension eligibility age cut
      off, results reveal large and significant reduction in intergenerational co
      residence of the extended family and increase in service consumption among
      elderly parents.

PMID- 29051721
TI  - A comparison of medical education in Germany and the United States: from applying
      to medical school to the beginnings of residency.
AB  - Both Germany and the United States of America have a long tradition of science
      and medical excellence reaching back as far as the nineteenth century. The same
      tribute must be paid to the medical educational system in both countries. Despite
      significant initial similarities and cross-inspiration, the paths from enrolling
      in a medical university to graduating as a medical doctor in Germany and the US
      seem to have become much different. To fill a void in literature, the authors'
      objective therefore is to delineate both structures of medical education in an up
      to-date review and examine their current differences and similarities. Recent
      medical publications, legal guidelines of governmental or official organizations,
      articles in media, as well as the authors' personal experiences are used as
      sources of this report. Tuition loans of over $200,000 are not uncommon for
      students in the US after graduating from medical schools, which are often private
      institutions. In Germany, however, the vast majority of medical universities are
      tax-funded and, for this reason, free of tuition. Significant differences and
      surprisingly multiple similarities exist between these two systems, despite one
      depending on government and the other on private organizations. Germany currently
      employs an integrated medical curriculum that typically begins right after high
      school and consists of a 2-year long pre-clinical segment teaching basic sciences
      and a 4-year clinical segment leading medical students to the practical aspects
      of medicine. On the other hand, the US education is a two-stage process. After
      successful completion of a Bachelor's degree in college, an American student goes
      through a 4-year medical program encompassing 2 years of basic science and 2
      years of clinical training. In this review, we will address some of these
      similarities and major differences.

PMID- 29051722
TI  - Event-Based Stereo Depth Estimation Using Belief Propagation.
AB  - Compared to standard frame-based cameras, biologically-inspired event-based
      sensors capture visual information with low latency and minimal redundancy. These
      event-based sensors are also far less prone to motion blur than traditional
      cameras, and still operate effectively in high dynamic range scenes. However,
      classical framed-based algorithms are not typically suitable for these event
      based data and new processing algorithms are required. This paper focuses on the
      problem of depth estimation from a stereo pair of event-based sensors. A fully
      event-based stereo depth estimation algorithm which relies on message passing is
      proposed. The algorithm not only considers the properties of a single event but
      also uses a Markov Random Field (MRF) to consider the constraints between the
      nearby events, such as disparity uniqueness and depth continuity. The method is
      tested on five different scenes and compared to other state-of-art event-based
      stereo matching methods. The results show that the method detects more stereo
      matches than other methods, with each match having a higher accuracy. The method
      can operate in an event-driven manner where depths are reported for individual
      events as they are received, or the network can be queried at any time to
      generate a sparse depth frame which represents the current state of the network.

PMID- 29051723
TI  - Autopilot, Mind Wandering, and the Out of the Loop Performance Problem.
AB  - To satisfy the increasing demand for safer critical systems, engineers have
      integrated higher levels of automation, such as glass cockpits in aircraft, power
      plants, and driverless cars. These guiding principles relegate the operator to a
      monitoring role, increasing risks for humans to lack system understanding. The
      out of the loop performance problem arises when operators suffer from complacency
      and vigilance decrement; consequently, when automation does not behave as
      expected, understanding the system or taking back manual control may be
      difficult. Close to the out of the loop problem, mind wandering points to the
      propensity of the human mind to think about matters unrelated to the task at
      hand. This article reviews the literature related to both mind wandering and the
      out of the loop performance problem as it relates to task automation. We
      highlight studies showing how these phenomena interact with each other while
      impacting human performance within highly automated systems. We analyze how this
      proximity is supported by effects observed in automated environment, such as
      decoupling, sensory attention, and cognitive comprehension decrease. We also show
      that this link could be useful for detecting out of the loop situations through
      mind wandering markers. Finally, we examine the limitations of the current
      knowledge because many questions remain open to characterize interactions between
      out of the loop, mind wandering, and automation.

PMID- 29051724
TI  - The Effect of Low-Frequency Physiological Correction on the Reproducibility and
      Specificity of Resting-State fMRI Metrics: Functional Connectivity, ALFF, and
      ReHo.
AB  - The resting-state fMRI (rs-fMRI) signal is affected by a variety of low-frequency
      physiological phenomena, including variations in cardiac-rate (CRV), respiratory
      volume (RVT), and end-tidal CO2 (PETCO2). While these effects have become better
      understood in recent years, the impact that their correction has on the quality
      of rs-fMRI measurements has yet to be clarified. The objective of this paper is
      to investigate the effect of correcting for CRV, RVT and PETCO2 on the rs-fMRI
      measurements. Nine healthy subjects underwent a test-retest rs-fMRI acquisition
      using repetition times (TRs) of 2 s (long-TR) and 0.323 s (short-TR), and the
      data were processed using eight different physiological correction strategies.
      Subsequently, regional homogeneity (ReHo), amplitude of low-frequency fluctuation
      (ALFF), and resting-state connectivity of the motor and default-mode networks are
      calculated for each strategy. Reproducibility is calculated using intra-class
      correlation and the Dice Coefficient, while the accuracy of functional
      connectivity measures is assessed through network separability, sensitivity and
      specificity. We found that: (1) the reproducibility of the rs-fMRI measures
      improved significantly after correction for PETCO2; (2) separability of
      functional networks increased after PETCO2 correction but was not affected by RVT
      and CRV correction; (3) the effect of physiological correction does not depend on
      the data sampling-rate; (4) the effect of physiological processes and correction
      strategies is network-specific. Our findings highlight limitations in our
      understanding of rs-fMRI quality measures, and underscore the importance of using
      multiple quality measures to determine the optimal physiological correction
      strategy.

PMID- 29051725
TI  - Song Processing in the Zebra Finch Auditory Forebrain Reflects Asymmetric
      Sensitivity to Temporal and Spectral Structure.
AB  - Despite being commonly referenced throughout neuroscientific research on
      songbirds, reports of hemispheric specialization in the processing of song remain
      controversial. The notion of such asymmetries in songbirds is further complicated
      by evidence that both cerebral hemispheres in humans may be specialized for
      different aspects of speech perception. Some studies suggest that the auditory
      neural substrates in the left and right hemispheres of humans process temporal
      and spectral elements within speech sounds, respectively. To determine whether
      songbirds process their conspecific songs in such a complementary, bilateral
      manner, we performed functional magnetic resonance imaging (fMRI) on 15
      isoflurane anesthetized adult male zebra finches (Taeniopygia guttata) while
      presenting them with (1) non-manipulated, (2) spectrally-filtered (reduced
      spectral structure), and (3) temporally-filtered (reduced temporal structure)
      conspecific song. Our results revealed sensitivity of both primary (Field L) and
      secondary (caudomedial nidopallium, NCM) auditory regions to changes in spectral
      and temporal structure of song. On the one hand, temporally-filtered song
      elicited a bilateral decrease in neural responses compared to the other stimulus
      types. On the other hand, spectrally filtered song elicited significantly greater
      responses in left Field L and NCM than temporally filtered or non-manipulated
      song while concurrently reducing the response relative to non-manipulated song in
      the right auditory forebrain. The latter hemispheric difference in sensitivity to
      manipulations of spectral structure in song, suggests that there is an asymmetry
      in spectral and temporal domain processing in the zebra finch auditory forebrain
      bearing some resemblance to what has been observed in human auditory cortex.

PMID- 29051726
TI  - Head Stabilization in the Pigeon: Role of Vision to Correct for Translational and
      Rotational Disturbances.
AB  - Stabilization of the head in animals with limited capacity to move their eyes is
      key to maintain a stable image on the retina. In many birds, including pigeons, a
      prominent example for the important role of head stabilization is the
      characteristic head-bobbing behavior observed during walking. Multimodal sensory
      feedback from the eyes, the vestibular system and proprioceptors in body and neck
      is required to control head stabilization. Here, we trained unrestrained pigeons
      (Columba livia) to stand on a perch that was sinusoidally moved with a motion
      platform along all three translational and three rotational degrees of freedom.
      We varied the frequency of the perturbation and we recorded the pigeons'
      responses under both light and dark conditions. Head, body, and platform
      movements were assessed with a high-speed motion capture system and the data were
      used to compute gain and phase of head and body movements in response to the
      perturbations. Comparing responses under dark and light conditions, we estimated
      the contribution of visual feedback to the control of the head. Our results show
      that the head followed the movement of the motion platform to a large extent
      during translations, but it was almost perfectly stabilized against rotations.
      Visual feedback only improved head stabilization during translations but not
      during rotations. The body compensated rotations around the forward-backward and
      the lateral axis, but did not contribute to head stabilization during
      translations and rotations around the vertical axis. From the results, we
      conclude that head stabilization in response to translations and rotations
      depends on different sensory feedback and that visual feedback plays only a
      limited role for head stabilization during standing.

PMID- 29051727
TI  - SYVN1, an ERAD E3 Ubiquitin Ligase, Is Involved in GABAAalpha1 Degradation
      Associated with Methamphetamine-Induced Conditioned Place Preference.
AB  - Abuse of methamphetamine (METH), a powerful addictive amphetamine-type stimulants
      (ATS), is becoming a global public health problem. The gamma-aminobutyric acid
      (GABA)ergic system plays a critical role in METH use disorders. By using rat METH
      conditioned place preference (CPP) model, we previously demonstrated that METH
      associated rewarding memory formation was associated with the reduction of
      GABAAalpha1 expression in the dorsal straitum (Dstr), however, the underlying
      mechanism was unclear. In the present study, we found that METH-induced CPP
      formation was accompanied by a significant increase in the expression of Synovial
      apoptosis inhibitor 1 (SYVN1), an endoplasmic reticulum (ER)-associated
      degradation (ERAD) E3 ubiquitin ligase, in the Dstr. The siRNA knockdown of SYVN1
      significantly increased GABAAalpha1 protein levels in both primary cultured
      neurons and rodent Dstr. Inhibition of proteasomal activity by MG132 and
      Lactacystin significantly increased GABAAalpha1 protein levels. We further found
      that SYVN1 knockdown increased GABAAalpha1 in the intra-ER, but not in the extra
      ER. Accordingly, endoplasmic reticulum stress (ERS)-associated Glucose-regulated
      protein 78 (GRP78) and C/EBP homologous protein (CHOP) increased. Thus, this
      study revealed that SYVN1, as the ERAD E3 ubiquitin ligase, was associated with
      Dstr GABAAalpha1 degradation induced by METH conditioned pairing.

PMID- 29051728
TI  - Exacerbation of Brain Injury by Post-Stroke Exercise Is Contingent Upon Exercise
      Initiation Timing.
AB  - Accumulating evidence has demonstrated that post-stroke physical rehabilitation
      may reduce morbidity. The effectiveness of post-stroke exercise, however, appears
      to be contingent upon exercise initiation. This study assessed the hypothesis
      that very early exercise exacerbates brain injury, induces reactive oxygen
      species (ROS) generation, and promotes energy failure. A total of 230 adult male
      Sprague-Dawley rats were subjected to middle cerebral artery (MCA) occlusion for
      2 h, and randomized into eight groups, including two sham injury control groups,
      three non-exercise and three exercise groups. Exercise was initiated after 6 h,
      24 h and 3 days of reperfusion. Twenty-four hours after completion of exercise
      (and at corresponding time points in non-exercise controls), infarct volumes and
      apoptotic cell death were examined. Early brain oxidative metabolism was
      quantified by examining ROS, ATP and NADH levels 0.5 h after completion of
      exercise. Furthermore, protein expressions of angiogenic growth factors were
      measured in order to determine whether post-stroke angiogenesis played a role in
      rehabilitation. As expected, ischemic stroke resulted in brain infarction,
      apoptotic cell death and ROS generation, and diminished NADH and ATP production.
      Infarct volumes and apoptotic cell death were enhanced (p < 0.05) by exercise
      that was initiated after 6 h of reperfusion, but decreased by late exercise (24
      h, 3 days). This exacerbated brain injury at 6 h was associated with increased
      ROS levels (p < 0.05), and decreased (p < 0.05) NADH and ATP levels. In
      conclusion, very early exercise aggravated brain damage, and early exercise
      induced energy failure with ROS generation may underlie the exacerbation of brain
      injury. These results shed light on the manner in which exercise initiation
      timing may affect post-stroke rehabilitation.

PMID- 29051729
TI  - Negative Influence of Motor Impairments on Upper Limb Movement Patterns in
      Children with Unilateral Cerebral Palsy. A Statistical Parametric Mapping Study.
AB  - Upper limb three-dimensional movement analysis (UL-3DMA) offers a reliable and
      valid tool to evaluate movement patterns in children with unilateral cerebral
      palsy (uCP). However, it remains unknown to what extent the underlying motor
      impairments explain deviant movement patterns. Such understanding is key to
      develop efficient rehabilitation programs. Although UL-3DMA has been shown to be
      a useful tool to assess movement patterns, it results in a multitude of data,
      challenging the clinical interpretation and consequently its implementation. UL
      3DMA reports are often reduced to summary metrics, such as average or peak values
      per joint. However, these metrics do not take into account the continuous nature
      of the data or the interdependency between UL joints, and do not provide phase
      specific information of the movement pattern. Moreover, summary metrics may not
      be sensitive enough to estimate the impact of motor impairments. Recently,
      Statistical Parametric Mapping (SPM) was proposed to overcome these problems. We
      collected UL-3DMA of 60 children with uCP and 60 typically developing children
      during eight functional tasks and evaluated the impact of spasticity and muscle
      weakness on UL movement patterns. SPM vector field analysis was used to analyze
      movement patterns at the level of five joints (wrist, elbow, shoulder, scapula,
      and trunk). Children with uCP showed deviant movement patterns in all joints
      during a large percentage of the movement cycle. Spasticity and muscle weakness
      negatively impacted on UL movement patterns during all tasks, which resulted in
      increased wrist flexion, elbow pronation and flexion, increased shoulder external
      rotation, decreased shoulder elevation with a preference for movement in the
      frontal plane and increased trunk internal rotation. Scapular position was
      altered during movement initiation, although scapular movements were not affected
      by muscle weakness or spasticity. In conclusion, we identified pathological
      movement patterns in children with uCP and additionally mapped the negative
      impact of spasticity and muscle weakness on these movement patterns, providing
      useful insights that will contribute to treatment planning. Last, we also
      identified a subset of the most relevant tasks for studying UL movements in
      children with uCP, which will facilitate the interpretation of UL-3DMA data and
      undoubtedly contribute to its clinical implementation.

PMID- 29051730
TI  - Dynamical Graph Theory Networks Methods for the Analysis of Sparse Functional
      Connectivity Networks and for Determining Pinning Observability in Brain
      Networks.
AB  - Neuroimaging in combination with graph theory has been successful in analyzing
      the functional connectome. However almost all analysis are performed based on
      static graph theory. The derived quantitative graph measures can only describe a
      snap shot of the disease over time. Neurodegenerative disease evolution is poorly
      understood and treatment strategies are consequently only of limited efficiency.
      Fusing modern dynamic graph network theory techniques and modeling strategies at
      different time scales with pinning observability of complex brain networks will
      lay the foundation for a transformational paradigm in neurodegnerative diseases
      research regarding disease evolution at the patient level, treatment response
      evaluation and revealing some central mechanism in a network that drives
      alterations in these diseases. We model and analyze brain networks as two-time
      scale sparse dynamic graph networks with hubs (clusters) representing the fast
      sub-system and the interconnections between hubs the slow sub-system. Alterations
      in brain function as seen in dementia can be dynamically modeled by determining
      the clusters in which disturbance inputs have entered and the impact they have on
      the large-scale dementia dynamic system. Observing a small fraction of specific
      nodes in dementia networks such that the others can be recovered is accomplished
      by the novel concept of pinning observability. In addition, how to control this
      complex network seems to be crucial in understanding the progressive abnormal
      neural circuits in many neurodegenerative diseases. Detecting the controlling
      regions in the networks, which serve as key nodes to control the aberrant
      dynamics of the networks to a desired state and thus influence the progressive
      abnormal behavior, will have a huge impact in understanding and developing
      therapeutic solutions and also will provide useful information about the
      trajectory of the disease. In this paper, we present the theoretical framework
      and derive the necessary conditions for (1) area aggregation and time-scale
      modeling in brain networks and for (2) pinning observability of nodes in dynamic
      graph networks. Simulation examples are given to illustrate the theoretical
      concepts.

PMID- 29051731
TI  - PARP-1 and p53 Regulate the Increased Susceptibility to Oxidative Death of
      Lymphocytes from MCI and AD Patients.
AB  - Mild cognitive impairment (MCI) is a clinically detectable initial stage of
      cognitive deterioration with a high conversion rate to dementia. There is
      increasing evidence that some of the cerebral alterations present in Alzheimer
      type dementia can be found in peripheral tissues. We have previously shown that
      lymphocytes from Alzheimer's disease (AD) patients have increased susceptibility
      to hydrogen peroxide (H2O2)-induced death that depends on dementia severity. We
      here investigated whether lymphocytes from MCI patients show increased
      vulnerability to death, and explored the involvement of Poly [ADP-ribose]
      polymerase (PARP-1) and p53 in the regulation of this process. Lymphocytes from
      16 MCI and 10 AD patients, and 15 healthy controls (HCs) were submitted to
      increasing concentrations of H2O2 for 20 h. Cell death was determined by flow
      cytometry, in the presence or absence of PARP-1 inhibitors (3-aminobenzamide (3
      ABA) or Nicotinamide (NAM)), or the p53 inhibitor (nutlin-3) or stabilizer
      (pifithrin-alpha). PARP-1 and p53 mRNA levels were determined by quantitative PCR
      (qPCR). Lymphocytes from MCI patients showed increased susceptibility to death,
      attaining intermediate values between AD and controls. PARP inhibitors -3-ABA and
      NAM- markedly protected from H2O2-induced death, making the difference between
      MCI and controls disappear, but not the difference between AD and controls. PARP
      1 mRNA expression was increased in MCI lymphocytes. Modulation of p53 with Nutlin
      3 or pifithrin-alpha did not modify the H2O2-induced death of lymphocytes from
      MCI or AD patients, but augmented the death in control lymphocytes attaining
      levels similar to MCI and AD. Accordingly, p53 mRNA expression was increased in
      AD and MCI lymphocytes compared to controls. In all, these results show that
      increased oxidative death is present in lymphocytes at the MCI stage. PARP-1 has
      a preponderant role, with complete death protection achieved with PARP inhibition
      in MCI lymphocytes, but not in AD, suggesting that PARP-1 might have a protective
      role. In addition, deregulations of the p53 pathway seem to contribute to the
      H2O2-induced death in MCI and AD lymphocytes, which show increased p53
      expression. The results showing a prominent protective role of PARP inhibitors
      opens the door to study the use of these agents to prevent oxidative death in MCI
      patients.

PMID- 29051732
TI  - Age-Related Frontal Periventricular White Matter Hyperintensities and miR-92a-3p
      Are Associated with Early-Onset Post-Stroke Depression.
AB  - Objective: To explore the correlationship among white matter hyperintensities
      (WMHs), miR-92a-3p and early-onset post-stroke depression (PSD). Methods: We
      recruited consecutively 238 patients with acute cerebral infarction and MRI
      examination in the Department of neurology, Ruijin hospital, Shanghai Jiaotong
      University School of Medicine. The diagnosis of early-onset PSD was made in
      accordance with DSM-IV criteria for depression in 2 weeks after stroke. Clinical
      information and assessments of stroke severity were recorded on admission. The
      analysis of plasma miR-92a-3p was performed using quantitative PCR at the same
      time. WMHs were evaluated by the Fazekas and Scheltens visual rating scales. The
      relationship among WMHs, miR-92a-3p and PSD were analyzed by SPSS 22.0 software.
      Results: Logistic regression demonstrated that periventricular WMHs (PVWMHs) in
      frontal caps was an independent risk factor with early-onset PSD (OR = 1.579, 95%
      CI: 1.040-2.397, p = 0.032). The age and numbers of lacunes were related to
      frontal PVWMHs. Plasma miR-92a-3p in the PSD group was higher compared with the
      non-depressed group. Receiver operating curve analysis revealed that miR-92a-3p
      could predict early-onset PSD with 90% sensitivity and 90% specificity. The
      higher miR-92a-3p trended toward association with greater frontal PVWMHs.
      Conclusion: Acute ischemic stroke patients with frontal PVWMHs or a high plasma
      miR-92a-3p at baseline were more likely to develop early-onset PSD. MiR-92a-3p
      might be involved in the white matter impairment and post-stroke depression.

PMID- 29051734
TI  - Overview on Patient Centricity in Cancer Care.
AB  - Successful implementation of treatment in cancer care partially depends on how
      patients' perspectives are taken into account, as preferences of health care
      professionals and patients may differ. Objectives of this exploratory research
      were (I) to identify patient preferences and values (PPVs) in cancer care as
      indicated by patient organizations (POs), (II) to determine how these PPVs are
      captured in cancer care guidelines and (III) to review how guidelines take into
      account these PPVs. Based on a survey developed and completed by 19 POs, a
      literature review was conducted to analyse how patient perspectives are
      incorporated in oncology treatment guidelines. Based on survey results
      traditional health technology assessment value propositions of oncology care,
      such as extended life, treatment-free remission and pain reduction, were also
      highly rated by POs. However, the heterogeneity of cancer PPVs were clearly
      reflected in the survey results. PPVs in cancer care guidelines were mostly
      limited to those micro-level aspects that are strictly related to health care
      provision, such as side-effects and comorbidities. Patient experience, emotional
      support and convenience of care were relatively neglected fields in the reviewed
      guidelines. Patient engagement was rarely presented in the guideline development
      phase. POs believe that patients should be encouraged to take an active role in
      their own care due to the heterogeneity of cancer patients and PPVs. Even if
      patient-centricity is a leading paradigm in cancer policy, based on our research
      it is not yet standard practice to include patients or POs at all appropriate
      levels of decision-making processes that are related to their health and well
      being. Patient engagement should be an integral part of cancer care decision
      making. This complexity must be reflected throughout policy making, avoiding a
      population level "one-size-fits-all" solution.

PMID- 29051733
TI  - System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and
      Huanglian for Diabetes Mellitus.
AB  - The rapidly increasing diabetes mellitus (DM) is becoming a major global public
      health issue. Traditional Chinese medicine (TCM) has a long history of the
      treatment of DM with good efficacy. Huangqi and Huanglian are one of the most
      frequently prescribed herbs for DM, and the combination of them occurs frequently
      in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix
      Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To
      address this problem, a feasible system pharmacology model based on chemical,
      pharmacokinetic and pharmacological data was developed via network construction
      approach to clarify the synergistic mechanisms of these two herbs. Forty-three
      active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and
      Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic
      profiles and biological activities were selected, interacting with 50 DM-related
      targets to provide potential synergistic therapeutic actions. Systematic analysis
      of the constructed networks revealed that these targets such as GLUT2, NOS2,
      PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin
      resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were
      mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ
      tissues, and whole blood. The contribution index of every active ingredient also
      indicated five compounds, including berberine (BBR), astragaloside IV (AIV),
      quercetin, palmatine, and astragalus polysaccharides, as the principal components
      of this herb combination. These results successfully explained the
      polypharmcological and synergistic mechanisms underlying the efficiency of
      Huangqi and Huanglian for the treatment of DM and its complications.

PMID- 29051735
TI  - The Impacts of Genistein and Daidzein on Estrogen Conjugations in Human Breast
      Cancer Cells: A Targeted Metabolomics Approach.
AB  - The beneficial effect of dietary soy food intake, especially for women diagnosed
      with breast cancer, is controversial, as in vitro data has shown that the soy
      isoflavones genistein and daidzein may even stimulate the proliferation of
      estrogen-receptor alpha positive (ERalpha+) breast cancer cells at low
      concentrations. As genistein and daidzein are known to inhibit key enzymes in the
      steroid metabolism pathway, and thus may influence levels of active estrogens, we
      investigated the impacts of genistein and daidzein on the formation of estrogen
      metabolites, namely 17beta-estradiol (E2), 17beta-estradiol-3-(beta-D
      glucuronide) (E2-G), 17beta-estradiol-3-sulfate (E2-S) and estrone-3-sulfate (E1
      S) in estrogen-dependent ERalpha+ MCF-7 cells. We found that both isoflavones
      were potent inhibitors of E1 and E2 sulfation (85-95% inhibition at 10 MUM), but
      impeded E2 glucuronidation to a lesser extent (55-60% inhibition at 10 MUM). The
      stronger inhibition of E1 and E2 sulfation compared with E2 glucuronidation was
      more evident for genistein, as indicated by significantly lower inhibition
      constants for genistein [Kis: E2-S (0.32 MUM) < E1-S (0.76 MUM) < E2-G (6.01
      MUM)] when compared with those for daidzein [Kis: E2-S (0.48 MUM) < E1-S (1.64
      MUM) < E2-G (7.31 MUM)]. Concomitant with the suppression of E1 and E2
      conjugation, we observed a minor but statistically significant increase in E2
      concentration of approximately 20%. As the content of genistein and daidzein in
      soy food is relatively low, an increased risk of breast cancer development and
      progression in women may only be observed following consumption of high-dose
      isoflavone supplements. Further long-term human studies monitoring free estrogens
      and their conjugates are therefore highly warranted to evaluate the potential
      side effects of high-dose genistein and daidzein, especially in patients
      diagnosed with ERalpha+ breast cancer.

PMID- 29051736
TI  - Novel Peripherally Restricted Cannabinoid 1 Receptor Selective Antagonist TXX-522
      with Prominent Weight-Loss Efficacy in Diet Induced Obese Mice.
AB  - The clinical development of the first generation of globally active cannabinoid 1
      receptor (CB1R) antagonists was suspended because of their adverse
      neuropsychiatric effects. Selective blockade of peripheral CB1Rs has the
      potential to provide a viable strategy for the treatment of severe obesity while
      avoiding these central nervous system side effects. In the current study, a novel
      compound (TXX-522) was rationally designed based on the parent nucleus of a
      classical CB1R-selective antagonist/inverse agonist, rimonabant (SR141716A).
      Docking assays indicate that TXX-522 was bound with the CB1R in a mode similar to
      that of SR141716A. TXX-522 showed good binding, CB1R-selectivity (over the CB2R),
      and functional antagonist activities in a range of in vitro molecular and
      cellular assays. In vivo analysis of the steady state distribution of TXX-522 in
      the rat brain and blood tissues and the assay of its functional effects on CB1R
      activity collectively showed that TXX-522 showed minimal brain penetration.
      Moreover, the in vivo pharmacodynamic study further revealed that TXX-522 had
      good oral bioavailability and a potent anti-obesity effect, and ameliorated
      insulin resistance in high-fat diet-induced obese mice. No impact on food intake
      was observed in this model, confirming the limited brain penetration of this
      compound. Thus, the current study indicates that TXX-522 is a novel and potent
      peripherally acting selective CB1R antagonist with the potential to control
      obesity and related metabolic disorders.

PMID- 29051737
TI  - Lack of Contribution of p66shc and Its Mitochondrial Translocation to Ischemia
      Reperfusion Injury and Cardioprotection by Ischemic Preconditioning.
AB  - Whereas high amounts of reactive oxygen species (ROS) contribute to cardiac
      damage following ischemia and reperfusion (IR), low amounts function as trigger
      molecules in the cardioprotection by ischemic preconditioning (IPC). The
      mitochondrial translocation and contribution of the hydrogen peroxide-generating
      protein p66shc in the cardioprotection by IPC is unclear yet. In the present
      study, we investigated the mitochondrial translocation of p66shc, addressed the
      impact of p66shc on ROS formation after IR, and characterized the role of p66shc
      in IR injury per se and in the cardioprotection by IPC. The amount of p66shc in
      subsarcolemmal (SSM) and interfibrillar mitochondria (IFM) isolated from wildtype
      mouse left ventricles (LV) was determined after 40 min normoxic perfusion and
      after 30 min ischemia and 10 min reperfusion without and with IPC. The p66shc
      content in SSM (in % of normoxic controls, n = 5) was 174 +/- 16% (n = 6, p <
      0.05) after IR, and was reduced to 128 +/- 13% after IPC (n = 6, p = ns). In IFM,
      the amount of p66shc remained unchanged (IR: 81 +/- 7%, n = 6; IPC: 110 +/- 5%, n
      = 6, p = ns). IR induced an increase in ROS formation in SSM and IFM isolated
      from mouse wildtype LV, which was more pronounced in SSM than in IFM (1.18 +/-
      0.18 vs. 0.81 +/- 0.16, n = 6, p < 0.05). In mitochondria from p66shc-knockout
      mice (p66shc-KO), the increase in ROS formation by IR was not different between
      SSM and IFM (0.90 +/- 0.11 vs. 0.73 +/- 0.08, n = 6, p = ns). Infarct size (in %
      of the left ventricle) was 51.7 +/- 2.9% in wildtype and 59.7 +/- 3.8% in p66shc
      KO hearts in vitro and was significantly reduced to 35.8 +/- 4.4% (wildtype) and
      34.7 +/- 5.6% (p66shc-KO) by IPC, respectively. In vivo, infarct size was 57.8 +/
      2.9% following IR (n = 9) and was reduced to 40.3 +/- 3.5% by IPC (n = 11, p <
      0.05) in wildtype mice. In p66shc-knockout mice, infarct sizes were similar to
      those measured in wildtype animals (IR: 56.2 +/- 4.3%, n = 11; IPC: 42.1 +/-
      3.9%, n = 13, p < 0.05). Taken together, the mitochondrial translocation of
      p66shc following IR and IPC differs between mitochondrial populations. However,
      similar infarct sizes after IR and preserved infarct size reductions by IPC in
      p66shc-KO mice suggest that p66shc-derived ROS are not involved in the
      cardioprotection by IPC nor do they contribute to IR injury per se.

PMID- 29051738
TI  - Early Seizure Detection Based on Cardiac Autonomic Regulation Dynamics.
AB  - Epilepsy is a neurological disorder that causes changes in the autonomic nervous
      system. Heart rate variability (HRV) reflects the regulation of cardiac activity
      and autonomic nervous system tone. The early detection of epileptic seizures
      could foster the use of new treatment approaches. This study presents a new
      methodology for the prediction of epileptic seizures using HRV signals.
      Eigendecomposition of HRV parameter covariance matrices was used to create an
      input for a support vector machine (SVM)-based classifier. We analyzed clinical
      data from 12 patients (9 female; 3 male; age 34.5 +/- 7.5 years), involving 34
      seizures and a total of 55.2 h of interictal electrocardiogram (ECG) recordings.
      Data from 123.6 h of ECG recordings from healthy subjects were used to test false
      positive rate per hour (FP/h) in a completely independent data set. Our
      methodological approach allowed the detection of impending seizures from 5 min to
      just before the onset of a clinical/electrical seizure with a sensitivity of
      94.1%. The FP rate was 0.49 h-1 in the recordings from patients with epilepsy and
      0.19 h-1 in the recordings from healthy subjects. Our results suggest that it is
      feasible to use the dynamics of HRV parameters for the early detection and,
      potentially, the prediction of epileptic seizures.

PMID- 29051739
TI  - Impaired Feedback Processing for Symbolic Reward in Individuals with Internet
      Game Overuse.
AB  - Reward processing, which plays a critical role in adaptive behavior, is impaired
      in addiction disorders, which are accompanied by functional abnormalities in
      brain reward circuits. Internet gaming disorder, like substance addiction, is
      thought to be associated with impaired reward processing, but little is known
      about how it affects learning, especially when feedback is conveyed by less
      salient motivational events. Here, using both monetary (+/-500 KRW) and symbolic
      (Chinese characters "right" or "wrong") rewards and penalties, we investigated
      whether behavioral performance and feedback-related neural responses are altered
      in Internet game overuse (IGO) group. Using functional MRI, brain responses for
      these two types of reward/penalty feedback were compared between young males with
      problems of IGO (IGOs, n = 18, mean age = 22.2 +/- 2.0 years) and age-matched
      control subjects (Controls, n = 20, mean age = 21.2 +/- 2.1) during a visuomotor
      association task where associations were learned between English letters and one
      of four responses. No group difference was found in adjustment of error responses
      following the penalty or in brain responses to penalty, for either monetary or
      symbolic penalties. The IGO individuals, however, were more likely to fail to
      choose the response previously reinforced by symbolic (but not monetary) reward.
      A whole brain two-way ANOVA analysis for reward revealed reduced activations in
      the IGO group in the rostral anterior cingulate cortex/ventromedial prefrontal
      cortex (vmPFC) in response to both reward types, suggesting impaired reward
      processing. However, the responses to reward in the inferior parietal region and
      medial orbitofrontal cortex/vmPFC were affected by the types of reward in the IGO
      group. Unlike the control group, in the IGO group the reward response was reduced
      only for symbolic reward, suggesting lower attentional and value processing
      specific to symbolic reward. Furthermore, the more severe the Internet gaming
      overuse symptoms in the IGO group, the greater the activations of the ventral
      striatum for monetary relative to symbolic reward. These findings suggest that
      IGO is associated with bias toward motivationally salient reward, which would
      lead to poor goal-directed behavior in everyday life.

PMID- 29051740
TI  - Challenges and Perspectives in Bridging In- and Outpatient Sectors: The
      Implementation of Two Alternative Models of Care and Their Effect on the Average
      Length of Stay.
AB  - New models of care aimed at reinforcing the outpatient sector have been
      introduced in Germany over the last few years. Initially, a subscription-based
      model ("integrated care") was introduced in 2012 in the Immanuel Klinik
      Rudersdorf, wherein patients had to actively subscribe to the integrated care
      program. This integrated care model was replaced after 2 years by a subscription
      free "model project," in which all patients insured by the contracting insurance
      company took part in the program. Data showed that the introduction of the
      integrated care program in the inpatient setting led to an increase of the
      average length of stay in this group. The switch to the model project corrected
      this unwanted effect but failed in significantly decreasing the average length of
      stay when compared to standard care. However, both the integrated care program
      and model project succeeded in reducing the length of stay in the day care
      setting. When adjusting for the sex and diagnosis proportions of each year, it
      was shown that diagnosis strongly influenced the average length of stay in both
      settings, whereas sex only slightly influenced the duration of stay in the
      inpatient setting. Thus, in spite of strong financial and clinical incentives,
      the introduction of the model project couldn't fulfill its primary purpose of
      shifting resources from the inpatient to the outpatient setting in the initial
      years. Possible explanations, including struggle against long-established
      traditions and reluctance to change, are discussed.

PMID- 29051741
TI  - Prediction of Quality of Life in Asian Patients with Schizophrenia: A Cross
      sectional Pilot Study.
AB  - BACKGROUND: There has been a shift in mental health services from an emphasis on
      treatment focused on reducing symptoms to a more holistic approach involving
      quality of life (QOL) and overall well-being. Many psychosocial variables are
      associated with QOL but a parsimonious framework is needed to deepen our
      understanding about the contribution of psychosocial factors in influencing the
      QOL of Asian patients with schizophrenia in Singapore. The study aimed to address
      the current gap in literature by analysis of QOL using available predictors in
      Asian patients with schizophrenia in Singapore. METHODS: 43 Singaporean patients
      diagnosed with schizophrenia were recruited at a large teaching hospital in
      Singapore from January to May 2010 and were invited to complete questionnaires.
      Of the sample, 65.1% were females, ages ranged from 18 to 65 (M = 44.60, SD =
      12.19). Available variables were subjected to regression analysis. FINDINGS: The
      data were analyzed using SPSS Version 23 with the alpha level set at 0.05. The
      final model with five predictors was significant in predicting QOL. Positive Re
      appraisal, Social Support, Avoidant Coping, Duration of Hospitalization, and
      Education accounted for 47.2% of the variance (Adjusted R2 = 40.0%) in QOL, F (5,
      37) = 6.60, p < 0.001. Those with post-secondary or higher education had higher
      QOL than those with secondary or lower education. Duration of hospitalization
      negatively predicted QOL. CONCLUSION: The findings were discussed in regards to
      clinical implications for informing interventions to enhance QOL in patients with
      schizophrenia.

PMID- 29051742
TI  - The Joint Action Effect on Memory as a Social Phenomenon: The Role of Cued
      Attention and Psychological Distance.
AB  - In contrast to individual tasks, a specific social setting is created when two
      partners work together on a task. How does such a social setting affect memory
      for task-related information? We addressed this issue in a distributed joint
      action paradigm, where two team partners respond to different types of
      information within the same task. Previous work has shown that joint action in
      such a task enhances memory for items that are relevant to the partner's task but
      not to the own task. By removing critical, non-social confounds, we wanted to
      pinpoint the social nature of this selective memory advantage. Specifically, we
      created joint task conditions in which participants were aware of the shared
      nature of the concurrent task but could not perceive sensory cues to the other's
      responses. For a differentiated analysis of the social parameters, we also varied
      the distance between partners. We found that the joint action effect emerged even
      without sensory cues from the partner, and it declined with increasing distance
      between partners. These results support the notion that the joint-action effect
      on memory is in its core driven by the experience of social co-presence, and does
      not simply emerge as a by-product of partner-generated sensory cues.

PMID- 29051743
TI  - Latent Factors in Attention Emerge from 9 Years of Age among Elementary School
      Children.
AB  - We explored the development of attention among elementary school children. Three
      hundred and sixty-five primary school children aged 7-12 years completed seven
      attention tests (alertness, focused attention, divided attention, attentional
      switching, sustained attention, spatial attention, and supervisory attention). A
      factor analysis indicated that there was no stable construct of attention among 7
      to 8-year-old children. However, from 9 years on, children's attention could be
      separated into perceptual and executive attention. Notably, however, the
      attention types included in these two factors differed from those among adults.

PMID- 29051744
TI  - Similarly Torn, Differentially Shorn? The Experience and Management of Conflict
      between Multiple Roles, Relationships, and Social Categories.
AB  - In three studies we examined the experience and management of conflict between
      different types of multiple identities. Participants described a conflict between
      pairs of role, relational, or social identities before rating the experience
      (i.e., magnitude, stress, and growth) and management of conflict on a newly
      developed scale assessing four strategies: reconciliation, where identities are
      integrated, realignment, where one identity is chosen over another, retreat,
      where both identities are avoided, and reflection, where fit (with others,
      situation) determines identity selection. In general, the types of identities
      mattered for conflict management but not its experience: Magnitude and growth did
      not differ, however, stress was greater for role identity conflicts (Study 3
      only) and participants endorsed the use of more realignment for role conflicts
      (Study 2) and more retreat for relational conflicts (Study 3) relative to other
      types of identity conflicts. Furthermore, findings suggested that the perceived
      flexibility of identities, not their importance or valence, were associated with
      realignment and retreat for roles and with retreat for relationships.
      Experiencing conflicts between multiple identities leaves people similarly torn,
      but multiple roles and relationships may be differentially shorn to manage
      conflict.

PMID- 29051745
TI  - Traumatic Brain Injury Severity, Neuropathophysiology, and Clinical Outcome:
      Insights from Multimodal Neuroimaging.
AB  - BACKGROUND: The relationship between the acute clinical presentation of patients
      with traumatic brain injury (TBI), long-term changes in brain structure prompted
      by injury and chronic functional outcome is insufficiently understood. In this
      preliminary study, we investigate how acute Glasgow coma score (GCS) and
      epileptic seizure occurrence after TBIs are statistically related to functional
      outcome (as quantified using the Glasgow Outcome Score) and to the extent of
      cortical thinning observed 6 months after the traumatic event. METHODS: Using
      multivariate linear regression, the extent to which the acute GCS and epileptic
      seizure occurrence (predictor variables) correlate with structural brain changes
      (relative cortical atrophy) was examined in a group of 33 TBI patients. The
      statistical significance of the correlation between relative cortical atrophy and
      the Glasgow Outcome Score was also investigated. RESULTS: A statistically
      significant correlative relationship between cortical thinning and the predictor
      variables (acute GCS and seizure occurrence) was identified in the study sample.
      Regions where the statistical model was found to have highest statistical
      reliability in predicting both gray matter atrophy and neurological outcome
      include the frontopolar, middle frontal, postcentral, paracentral, middle
      temporal, angular, and lingual gyri. In addition, relative atrophy and GOS were
      also found to be significantly correlated over large portions of the cortex.
      CONCLUSION: This study contributes to our understanding of the relationship
      between clinical descriptors of acute TBI, the extent of injury-related chronic
      brain changes and neurological outcome. This is partly because the brain areas
      where cortical thinning was found to be correlated with GCS and with seizure
      occurrence are implicated in executive control, sensory function, motor acuity,
      memory, and language, all of which may be affected by TBI. Thus, our
      quantification suggests the existence of a statistical relationship between acute
      clinical presentation, on the one hand, and structural/functional brain features
      which are particularly susceptible to post-injury degradation, on the other hand.

PMID- 29051746
TI  - Commentary: Efficacy of Follicle-Stimulating Hormone (FSH) Alone, FSH +
      Luteinizing Hormone, Human Menopausal Gonadotropin or FSH + Human Chorionic
      Gonadotropin on Assisted Reproductive Technology Outcomes in the "Personalized"
      Medicine Era: A Meta-analysis.

PMID- 29051747
TI  - pirABvp -Bearing Vibrio parahaemolyticus and Vibrio campbellii Pathogens Isolated
      from the Same AHPND-Affected Pond Possess Highly Similar Pathogenic Plasmids.
AB  - Acute hepatopancreatic necrosis disease (AHPND) is a severe shrimp disease
      originally shown to be caused by virulent strains of Vibrio parahaemolyticus
      (VPAHPND). Rare cases of AHPND caused by Vibrio species other than V.
      parahaemolyticus were reported. We compared an AHPND-causing V. campbellii
      (VCAHPND) and a VPAHPND isolate from the same AHPND-affected pond. Both strains
      are positive for the virulence genes pirABvp . Immersion challenge test with
      Litopenaeus vannamei indicated the two strains possessed similar pathogenicity.
      Complete genome comparison showed that the pirABvp -bearing plasmids in the two
      strains were highly homologous, and they both shared high homologies with plasmid
      pVA1, the reported pirABvp -bearing plasmid. Conjugation and DNA-uptake genes
      were found on the pVA1-type plasmids and the host chromosomes, respectively,
      which may facilitate the dissemination of pirABvp . Novel variations likely
      driven by ISVal1 in the genetic contexts of the pirABvp genes were found in the
      two strains. Moreover, the VCAHPND isolate additionally contains multiple
      antibiotic resistance genes, which may bring difficulties to control its future
      outbreak. The dissemination of the pirABvp in non-parahaemolyticus Vibrio also
      rises the concern of missing detection in industrial settings since the isolation
      method currently used mainly targeting V. parahaemolyticus. This study provides
      timely information for better understanding of the causes of AHPND and molecular
      epidemiology of pirABvp and also appeals for precautions to encounter the
      dissemination of the hazardous genes.

PMID- 29051748
TI  - Retrotransposon Domestication and Control in Dictyostelium discoideum.
AB  - Transposable elements, identified in all eukaryotes, are mobile genetic units
      that can change their genomic position. Transposons usually employ an excision
      and reintegration mechanism, by which they change position, but not copy number.
      In contrast, retrotransposons amplify via RNA intermediates, increasing their
      genomic copy number. Hence, they represent a particular threat to the structural
      and informational integrity of the invaded genome. The social amoeba
      Dictyostelium discoideum, model organism of the evolutionary Amoebozoa
      supergroup, features a haploid, gene-dense genome that offers limited space for
      damage-free transposition. Several of its contemporary retrotransposons display
      intrinsic integration preferences, for example by inserting next to transfer RNA
      genes or other retroelements. Likely, any retrotransposons that invaded the
      genome of the amoeba in a non-directed manner were lost during evolution, as this
      would result in decreased fitness of the organism. Thus, the positional
      preference of the Dictyostelium retroelements might represent a domestication of
      the selfish elements. Likewise, the reduced danger of such domesticated
      transposable elements led to their accumulation, and they represent about 10% of
      the current genome of D. discoideum. To prevent the uncontrolled spreading of
      retrotransposons, the amoeba employs control mechanisms including RNA
      interference and heterochromatization. Here, we review TRE5-A, DIRS-1 and Skipper
      1, as representatives of the three retrotransposon classes in D. discoideum,
      which make up 5.7% of the Dictyostelium genome. We compile open questions with
      respect to their mobility and cellular regulation, and suggest strategies, how
      these questions might be addressed experimentally.

PMID- 29051749
TI  - Phloroglucinol Degradation in the Rumen Promotes the Capture of Excess Hydrogen
      Generated from Methanogenesis Inhibition.
AB  - Strategies to manage metabolic hydrogen ([H]) in the rumen should be considered
      when reducing ruminant methane (CH4) emissions. However, little is known about
      the use of dietary treatments to stimulate rumen microorganisms capable of
      capturing the [H] available when CH4 is inhibited in vivo. The effects of the
      phenolic compound phloroglucinol on CH4 production, [H] flows and subsequent
      responses in rumen fermentation and microbial community composition when
      methanogenesis is inhibited were investigated in cattle. Eight rumen fistulated
      Brahman steers were randomly allocated in two groups receiving chloroform as an
      antimethanogenic compound for 21 days. Following that period one group received
      chloroform + phloroglucinol for another 16 days, whilst the other group received
      only chloroform during the same period. The chloroform treatment resulted in a
      decrease in CH4 production and an increase in H2 expelled with a shift in rumen
      fermentation toward higher levels of propionate and formate and lower levels of
      acetate at day 21 of treatment. Bacterial operational taxonomic units (OTUs)
      assigned to Prevotella were promoted whilst Archaea and Synergistetes OTUs were
      decreased with the chloroform treatment as expected. The shift toward formate
      coincided with increases in Ruminococcus flavefaciens, Butyrivibrio fibrisolvens,
      and Methanobrevibacter ruminantium species. The addition of chloroform +
      phloroglucinol in the rumen resulted in a decrease of H2 expelled (g) per kg of
      DMI and moles of H2 expelled per mol of CH4 decreased compared with the
      chloroform only treated animals. A shift toward acetate and a decrease in formate
      were observed for the chloroform + phloroglucinol-treated animals at day 37.
      These changes in the rumen fermentation profile were accompanied by a relative
      increase of OTUs assigned to Coprococcus spp., which could suggest this genus is
      a significant contributor to the metabolism of this phenolic compound in the
      rumen. This study demonstrates for the first time in vivo that under
      methanogenesis inhibition, H2 gas accumulation can be decreased by redirecting
      [H] toward alternative sinks through the nutritional stimulation of specific
      microbial groups. This results in the generation of metabolites of value for the
      host while also helping to maintain a low H2 partial pressure in the methane
      inhibited rumen.

PMID- 29051750
TI  - Epidemiology of Extended-Spectrum beta-Lactamase-Producing E. coli and Vancomycin
      Resistant Enterococci in the Northern Dutch-German Cross-Border Region.
AB  - Objectives: To reveal the prevalence and epidemiology of extended-spectrum beta
      lactamase (ESBL)- and/or plasmid AmpC (pAmpC)- and carbapenemase (CP) producing
      Enterobacteriaceae and vancomycin-resistant enterococci (VRE) across the Northern
      Dutch-German border region. Methods: A point-prevalence study on ESBL/pAmpC/CP
      producing Enterobacteriaceae and VRE was carried out in hospitalized patients in
      the Northern Netherlands (n = 445, 2012-2013) and Germany (n = 242, 2012).
      Healthy individuals from the Dutch community (n = 400, 2010-2012) were also
      screened. In addition, a genome-wide gene-by-gene approach was applied to study
      the epidemiology of ESBL-Escherichia coli and VRE. Results: A total of 34
      isolates from 27 patients (6.1%) admitted to Dutch hospitals were ESBL/pAmpC
      positive and 29 ESBL-E. coli, three pAmpC-E. coli, one ESBL-Enterobacter cloacae,
      and one pAmpC-Proteus mirabilis were found. In the German hospital, 18 isolates
      (16 E. coli and 2 Klebsiella pneumoniae) from 17 patients (7.7%) were ESBL
      positive. In isolates from the hospitalized patients CTX-M-15 was the most
      frequently detected ESBL-gene. In the Dutch community, 11 individuals (2.75%)
      were ESBL/pAmpC positive: 10 ESBL-E. coli (CTX-M-1 being the most prevalent gene)
      and one pAmpC E. coli. Six Dutch (1.3%) and four German (3.9%) hospitalized
      patients were colonized with VRE. Genetic relatedness by core genome multi-locus
      sequence typing (cgMLST) was found between two ESBL-E. coli isolates from Dutch
      and German cross-border hospitals and between VRE isolates from different
      hospitals within the same region. Conclusion: The prevalence of ESBL/pAmpC
      Enterobacteriaceae was similar in hospitalized patients across the Dutch-German
      border region, whereas VRE prevalence was slightly higher on the German side. The
      overall prevalence of the studied pathogens was lower in the community than in
      hospitals in the Northern Netherlands. Cross-border transmission of ESBL-E. coli
      and VRE seems unlikely based on cgMLST analysis, however continuous monitoring is
      necessary to control their spread and stay informed about their epidemiology.

PMID- 29051751
TI  - Evaluation of Different PCR-Based Assays and LAMP Method for Rapid Detection of
      Phytophthora infestans by Targeting the Ypt1 Gene.
AB  - Late blight, caused by the oomycete Phytophthora infestans, is one of the most
      devastating diseases affecting potato and tomato worldwide. Early diagnosis of
      the P. infestans pathogen causing late blight should be the top priority for
      addressing disease epidemics and management. In this study, we performed a loop
      mediated isothermal amplification (LAMP) assay, conventional polymerase chain
      reaction (PCR), nested PCR, and real-time PCR to verify and compare the
      sensitivity and specificity of the reaction based on the Ypt1 (Ras-related
      protein) gene of P. infestans. In comparison with the PCR-based assays, the LAMP
      technique led to higher specificity and sensitivity, using uncomplicated
      equipment with an equivalent time frame. All 43 P. infestans isolates, yielded
      positive detection results using LAMP assay showing no cross reaction with other
      Phytophthora spp., oomycetes or fungal pathogens. The LAMP assay yielded the
      lowest detectable DNA concentration (1.28 * 10-4 ng MUL-1), being 10 times more
      sensitive than nested PCR (1.28 * 10-3 ng MUL-1), 100 times more sensitive than
      real-time PCR (1.28 * 10-2 ng MUL-1) and 103 times more sensitive than the
      conventional PCR assay (1.28 * 10-1 ng MUL-1). In the field experiment, the LAMP
      assay outperformed the other tests by amplifying only diseased tissues (leaf and
      stem), and showing no positive reaction in healthy tissues. Overall, the LAMP
      assay developed in this study provides a specific, sensitive, simple, and
      effective visual method for detection of the P. infestans pathogen, and is
      therefore suitable for application in early prediction of the disease to reduce
      the risk of epidemics.

PMID- 29051752
TI  - ICESag37, a Novel Integrative and Conjugative Element Carrying Antimicrobial
      Resistance Genes and Potential Virulence Factors in Streptococcus agalactiae.
AB  - ICESag37, a novel integrative and conjugative element carrying multidrug
      resistance and potential virulence factors, was characterized in a clinical
      isolate of Streptococcus agalactiae. Two clinical strains of S. agalactiae, Sag37
      and Sag158, were isolated from blood samples of new-borns with bacteremia. Sag37
      was highly resistant to erythromycin and tetracycline, and susceptible to
      levofloxacin and penicillin, while Sag158 was resistant to tetracycline and
      levofloxacin, and susceptible to erythromycin. Transfer experiments were
      performed and selection was carried out with suitable antibiotic concentrations.
      Through mating experiments, the erythromycin resistance gene was found to be
      transferable from Sag37 to Sag158. SmaI-PFGE revealed a new SmaI fragment,
      confirming the transfer of the fragment containing the erythromycin resistance
      gene. Whole genome sequencing and sequence analysis revealed a mobile element,
      ICESag37, which was characterized using several molecular methods and in silico
      analyses. ICESag37 was excised to generate a covalent circular intermediate,
      which was transferable to S. agalactiae. Inverse PCR was performed to detect the
      circular form. A serine family integrase mediated its chromosomal integration
      into rumA, which is a known hotspot for the integration of streptococcal ICEs.
      The integration site was confirmed using PCR. ICESag37 carried genes for
      resistance to multiple antibiotics, including erythromycin [erm(B)], tetracycline
      [tet(O)], and aminoglycosides [aadE, aphA, and ant(6)]. Potential virulence
      factors, including a two-component signal transduction system (nisK/nisR), were
      also observed in ICESag37. S1-PFGE analysis ruled out the existence of plasmids.
      ICESag37 is the first ICESa2603 family-like element identified in S. agalactiae
      carrying both resistance and potential virulence determinants. It might act as a
      vehicle for the dissemination of multidrug resistance and pathogenicity among S.
      agalactiae.

PMID- 29051753
TI  - An H-NS Family Protein, Sfh, Regulates Acid Resistance by Inhibition of Glutamate
      Decarboxylase Expression in Shigella flexneri 2457T.
AB  - The glutamate-dependent acid-resistance system is the most effective acid
      tolerance pathway in Shigella, allowing survival in extremely acidic
      environments. However, the regulation of this system in Shigella remains elusive.
      In the current study, we identified significant differences in the levels of
      glutamate decarboxylase between three Shigella flexneri strains with different
      levels of acid resistance using blue native-polyacrylamide gel electrophoresis
      (PAGE) and isoelectric focusing (IEF)/sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis. The results showed that the degree of acid
      resistance and the levels of GadA/B were significantly lower in strain 2457T
      compared with two other S. flexneri strains. It has been reported that plasmid
      pSf-R27 is expressed in strain 2457T but not in the other 142 sequenced S.
      flexneri isolates. pSf-R27 encodes protein Sfh, which belongs to a family of
      histone-like nucleoid-structuring (H-NS) proteins that participate in the
      transcriptional control of glutamate-dependent acid resistance, implicating pSf
      R27 in the lower acid resistance of strain 2457T. Transformation of pSf-R27 or
      sfh alone into strain 301 resulted in decreased expression of GadA/B in the
      recombinant strains. Thus, we confirmed that H-NS family protein Sfh, bound to
      the gadA/B regulatory region and regulates the expression of glutamate
      decarboxylase at the transcriptional level. We also examined the acid tolerance
      of the wild-type and recombinant strains using flow cytometry and determined that
      the acid tolerance of S. flexneri is closely related to the expression of GadA/B.
      These findings further our understanding of the acid tolerance of S. flexneri,
      especially via the glutamate-dependent pathway.

PMID- 29051754
TI  - A Cellular Fusion Cascade Regulated by LaeA Is Required for Sclerotial
      Development in Aspergillus flavus.
AB  - Aspergillus flavus is a saprophytic soil fungus that poses a serious threat
      worldwide as it contaminates many food and feed crops with the carcinogenic
      mycotoxin called aflatoxin. This pathogen persists as sclerotia in the soil which
      enables fungal survival in harsh environmental conditions. Sclerotia formation by
      A. flavus depends on successful cell communication and hyphal fusion events. Loss
      of LaeA, a conserved developmental regulator in fungi, abolishes sclerotia
      formation in this species whereas overexpression (OE) of laeA results in enhanced
      sclerotia production. Here we demonstrate that sclerotia loss and inability to
      form heterokaryons in A. flavusDeltalaeA is mediated by homologs of the
      Neurospora crassa ham (hyphal anastomosis) genes termed hamE-I in A. flavus. LaeA
      positively regulates ham gene expression and deletion of hamF, G, H, or I
      phenocopies DeltalaeA as demonstrated by heterokaryon and sclerotia loss and
      reduced aflatoxin synthesis and virulence of these mutants. Deletion of hamE
      showed a less severe phenotype. hamE-I homologs are positively regulated by the
      clock controlled transcription factor ADV-1 in N. crassa. Similarly, the ADV-1
      homolog NosA regulates hamE-I expression in A. flavus, is required for sclerotial
      development and is itself positively regulated by LaeA. We speculate that a
      putative LaeA>NosA>fusion cascade underlies the previously described circadian
      clock regulation of sclerotia production in A. flavus.

PMID- 29051755
TI  - Estimating Primary Production of Picophytoplankton Using the Carbon-Based Ocean
      Productivity Model: A Preliminary Study.
AB  - Picophytoplankton are acknowledged to contribute significantly to primary
      production (PP) in the ocean while now the method to measure PP of
      picophytoplankton (PPPico) at large scales is not yet well established. Although
      the traditional 14C method and new technologies based on the use of stable
      isotopes (e.g., 13C) can be employed to accurately measure in situ PPPico, the
      time-consuming and labor-intensive shortage of these methods constrain their
      application in a survey on large spatiotemporal scales. To overcome this
      shortage, a modified carbon-based ocean productivity model (CbPM) is proposed for
      estimating the PPPico whose principle is based on the group-specific abundance,
      cellular carbon conversion factor (CCF), and temperature-derived growth rate of
      picophytoplankton. Comparative analysis showed that the estimated PPPico using
      CbPM method is significantly and positively related (r2 = 0.53, P < 0.001, n =
      171) to the measured 14C uptake. This significant relationship suggests that CbPM
      has the potential to estimate the PPPico over large spatial and temporal scales.
      Currently this model application may be limited by the use of invariant cellular
      CCF and the relatively small data sets to validate the model which may introduce
      some uncertainties and biases. Model performance will be improved by the use of
      variable conversion factors and the larger data sets representing diverse growth
      conditions. Finally, we apply the CbPM-based model on the collected data during
      four cruises in the Bohai Sea in 2005. Model-estimated PPPico ranged from 0.1 to
      11.9, 29.9 to 432.8, 5.5 to 214.9, and 2.4 to 65.8 mg C m-2 d-1 during March,
      June, September, and December, respectively. This study shed light on the
      estimation of global PPPico using carbon-based production model.

PMID- 29051756
TI  - Genomic GC-Content Affects the Accuracy of 16S rRNA Gene Sequencing Based
      Microbial Profiling due to PCR Bias.
AB  - Profiling of microbial community composition is frequently performed by partial
      16S rRNA gene sequencing on benchtop platforms following PCR amplification of
      specific hypervariable regions within this gene. Accuracy and reproducibility of
      this strategy are two key parameters to consider, which may be influenced during
      all processes from sample collection and storage, through DNA extraction and PCR
      based library preparation to the final sequencing. In order to evaluate both the
      reproducibility and accuracy of 16S rRNA gene based microbial profiling using the
      Ion Torrent PGM platform, we prepared libraries and performed sequencing of a
      well-defined and validated 20-member bacterial DNA mock community on five
      separate occasions and compared results with the expected even distribution. In
      general the applied method had a median coefficient of variance of 11.8% (range
      5.5-73.7%) for all 20 included strains in the mock community across five separate
      sequencing runs, with underrepresented strains generally showing the largest
      degree of variation. In terms of accuracy, mock community species belonging to
      Proteobacteria were underestimated, whereas those belonging to Firmicutes were
      mostly overestimated. This could be explained partly by premature read
      truncation, but to larger degree their genomic GC-content, which correlated
      negatively with the observed relative abundances, suggesting a PCR bias against
      GC-rich species during library preparation. Increasing the initial denaturation
      time during the PCR amplification from 30 to 120 s resulted in an increased
      average relative abundance of the three mock community members with the highest
      genomic GC%, but did not significantly change the overall evenness of the
      community distribution. Therefore, efforts should be made to optimize the PCR
      conditions prior to sequencing in order to maximize accuracy.

PMID- 29051757
TI  - Role of Gut Microbiota on Cardio-Metabolic Parameters and Immunity in Coronary
      Artery Disease Patients with and without Type-2 Diabetes Mellitus.
AB  - Gut microbiota composition has been reported as a factor linking host metabolism
      with the development of cardiovascular diseases (CVD) and intestinal immunity.
      Such gut microbiota has been shown to aggravate CVD by contributing to the
      production of trimethylamine N-oxide (TMAO), which is a pro-atherogenic compound.
      Treg cells expressing the transcription factor Forkhead box protein P3 (FoxP3)
      play an essential role in the regulation of immune responses to commensal
      microbiota and have an atheroprotective role. However, the aim of this study was
      to analyze the role of gut microbiota on cardio-metabolic parameters and immunity
      in coronary artery disease (CAD) patients with and without type-2 diabetes
      mellitus (DM2). The study included 16 coronary CAD-DM2 patients, and 16 age, sex,
      and BMI matched CAD patients without DM2 (CAD-NDM2). Fecal bacterial DNA was
      extracted and analyzed by sequencing in a GS Junior 454 platform followed by a
      bioinformatic analysis (QIIME and PICRUSt). The present study indicated that the
      diversity and composition of gut microbiota were different between the CAD-DM2
      and CAD-NDM2 patients. The abundance of phylum Bacteroidetes was lower, whereas
      the phyla Firmicutes and Proteobacteria were higher in CAD-DM2 patients than
      those in the CAD-NDM2 group. CAD-DM2 patients had significantly less beneficial
      or commensal bacteria (such as Faecalibacterium prausnitzii and Bacteroides
      fragilis) and more opportunistic pathogens (such as Enterobacteriaceae,
      Streptococcus, and Desulfovibrio). Additionally, CAD-DM2 patients had
      significantly higher levels of plasma zonulin, TMAO, and IL-1B and significantly
      lower levels of IL-10 and FOXP3 mRNA expression than CAD-NDM2. Moreover, in the
      CAD-MD2 group, the increase in Enterobacteriaceae and the decrease in
      Faecalibacterium prausnitzii were significantly associated with the increase in
      serum TMAO levels, while the decrease in the abundance of Bacteroides fragilis
      was associated with the reduction in the FOXP3 mRNA expression, implicated in the
      development and function of Treg cells. These results suggest that the presence
      of DM2 is related to an impaired regulation of the immune system in CAD patients,
      mediated in part by the gut microbiota composition and functionality and the
      production and effects of their gut microbiota derived molecules.

PMID- 29051758
TI  - Identification of YfiH and the Catalase CatA As Polyphenol Oxidases of Aeromonas
      media and CatA as a Regulator of Pigmentation by Its Peroxyl Radical Scavenging
      Capacity.
AB  - Pyomelanin is the major constituent of pigment in melanogenic Aeromonas strains
      of bacteria. However, eumelanin, synthesized from tyrosine via L-DOPA and
      polyphenol oxidases (PPOs), may also be present in this genus since L-DOPA is
      frequently detected in culture fluids of several species. To address this
      question, we used a deletion mutant of Aeromonas media strain WS, in which
      pyomelanin synthesis is completely blocked under normal culture conditions. When
      tyrosine was supplied to the medium, we observed residual melanin accumulation,
      which we interpret as evidence for existence of the DOPA-melanin pathway. We
      traced enzymatic activity in this bacterium using native-polyacrylamide gel
      electrophoresis. Two PPOs: YfiH, a laccase-like protein, and CatA, a catalase,
      were identified. However, neither protein was critical for the residual
      pigmentation in pyomelanin-deficient mutant. We speculate that eumelanin
      synthesis may require other unknown enzymes. Deletion of yfiH did not affect
      pigmentation in A. media strain WS, while deletion of the CatA-encoding gene katE
      resulted in a reduction of melanin accumulation, but it started 9 h earlier than
      in the wild-type. Since catalases regulate reactive oxygen species levels during
      melanogenesis, we speculated that CatA affects pigmentation through its peroxyl
      radical scavenging capacity. Consistent with this, expression of the catalases
      Hpi or Hpii from Escherichia coli in the katE deletion strain of A. media strain
      WS restored pigmentation to the wild-type level. Hpi and Hpii also exhibited PPO
      activity, suggesting that catalase may represent a new class of PPOs.

PMID- 29051759
TI  - IFNgamma Enhances CD64-Potentiated Phagocytosis of Treponema pallidum Opsonized
      with Human Syphilitic Serum by Human Macrophages.
AB  - Syphilis is a multi-stage, sexually transmitted disease caused by the spirochete
      Treponema pallidum (Tp). Considered broadly, syphilis can be conceptualized as a
      dualistic process in which spirochete-driven inflammation, the cause of clinical
      manifestations, coexists to varying extents with bacterial persistence.
      Inflammation is elicited in the tissues, along with the persistence of
      spirochetes to keep driving a robust immune response while evading host defenses;
      this duality is best exemplified during the florid, disseminated stage called
      secondary syphilis (SS). SS lesions typically contain copious amounts of
      spirochetes along with a mixed cellular infiltrate consisting of CD4+ T cells,
      CD8+ T cells, NK cells, plasma cells, and macrophages. In the rabbit model, Tp
      are cleared by macrophages via antibody-mediated opsonophagocytosis. Previously,
      we demonstrated that human syphilitic serum (HSS) promotes efficient uptake of Tp
      by human monocytes and that opsonophagocytosis of Tp markedly enhances cytokine
      production. Herein, we used monocyte-derived macrophages to study Tp-macrophage
      interactions ex vivo. In the absence of HSS, monocyte-derived macrophages
      internalized low numbers of Tp and secreted little cytokine (e.g., TNF). By
      contrast, these same macrophages internalized large numbers of unopsonized
      Borrelia burgdorferi and secreted robust levels of cytokines. Maturation of
      macrophages with M-CSF and IFNgamma resulted in a macrophage phenotype with
      increased expression of HLA-DR, CD14, inducible nitric oxide synthase, TLR2,
      TLR8, and the Fcgamma receptors (FcgammaR) CD64 and CD16, even in the absence of
      LPS. Importantly, IFNgamma-polarized macrophages resulted in a statistically
      significant increase in opsonophagocytosis of Tp accompanied by enhanced
      production of cytokines, macrophage activation markers (CD40, CD80), TLRs (TLR2,
      TLR7, TLR8), chemokines (CCL19, CXCL10, CXCL11), and TH1-promoting cytokines (IL
      12, IL-15). Finally, the blockade of FcgammaRs, primarily CD64, significantly
      diminished spirochetal uptake and proinflammatory cytokine secretion by IFNgamma
      stimulated macrophages. Our ex vivo studies demonstrate the importance of CD64
      potentiated uptake of opsonized Tp and suggest that IFNgamma-activated
      macrophages have an important role in the context of early syphilis. Our study
      results also provide an ex vivo surrogate system for use in future syphilis
      vaccine studies.

PMID- 29051761
TI  - Predicting Risk of Infection in Patients with Newly Diagnosed Multiple Myeloma:
      Utility of Immune Profiling.
AB  - BACKGROUND: A translational study in patients with myeloma to determine the
      utility of immune profiling to predict infection risk in patients with
      hematological malignancy was conducted. METHODS: Baseline, end of induction, and
      maintenance peripheral blood mononuclear cells from 40 patients were evaluated.
      Immune cell populations and cytokines released from 1 * 106 cells/ml cultured in
      the presence of a panel of stimuli (cytomegalovirus, influenza, S. pneumoniae,
      phorbol myristate acetate/ionomycin) and in media alone were quantified. Patient
      characteristics and infective episodes were captured from clinical records.
      Immunological variables associated with increased risk for infection in the 3
      month period following sample collection were identified using univariate
      analysis (p < 0.05) and refined with multivariable analysis to define a
      predictive immune profile. RESULTS: 525 stimulant samples with 19,950 stimulant
      cytokine combinations across three periods were studied, including 61 episodes of
      infection. Mitogen-stimulated release of IL3 and IL5 were significantly
      associated with increased risk for subsequent infection during maintenance
      therapy. A lower Th1/Th2 ratio and higher cytokine response ratios for IL5 and
      IL13 during maintenance therapy were also significantly associated with increased
      risk for infection. On multivariable analysis, only IL5 in response to mitogen
      stimulation was predictive of infection. The lack of cytokine response and
      numerical value of immune cells were not predictive of infection. CONCLUSION:
      Profiling cytokine release in response to mitogen stimulation can assist with
      predicting subsequent onset of infection in patients with hematological
      malignancy during maintenance therapy.

PMID- 29051760
TI  - Interplay of GTPases and Cytoskeleton in Cellular Barrier Defects during Gut
      Inflammation.
AB  - An essential role of the intestine is to build and maintain a barrier preventing
      the luminal gut microbiota from invading the host. This involves two coordinated
      physical and immunological barriers formed by single layers of intestinal
      epithelial and endothelial cells, which avoid the activation of local immune
      responses or the systemic dissemination of microbial agents, and preserve tissue
      homeostasis. Accordingly, alterations of epithelial and endothelial barrier
      functions have been associated with gut inflammation, for example during
      inflammatory bowel disease (IBD). The discriminative control of nutriment uptake
      and sealing toward potentially pathological microorganisms requires a profound
      regulation of para- and transcellular permeability. On the subcellular level, the
      cytoskeleton exerts key regulatory functions in the maintenance of cellular
      barriers. Increased epithelial/endothelial permeability occurs primarily as a
      result of a reorganization of cytoskeletal-junctional complexes. Pro-inflammatory
      mediators such as cytokines can induce cytoskeletal rearrangements, causing
      inflammation-dependent defects in gut barrier function. In this context, small
      GTPases of the Rho family and large GTPases from the Dynamin superfamily appear
      as major cellular switches regulating the interaction between intercellular
      junctions and actomyosin complexes, and in turn cytoskeleton plasticity.
      Strikingly, some of these proteins, such as RhoA or guanylate-binding protein-1
      (GBP-1) have been associated with gut inflammation and IBD. In this review, we
      will summarize the role of small and large GTPases for cytoskeleton plasticity
      and epithelial/endothelial barrier in the context of gut inflammation.

PMID- 29051762
TI  - Specific Pathogen Recognition by Multiple Innate Immune Sensors in an
      Invertebrate.
AB  - Detection of pathogens by all living organisms is the primary step needed to
      implement a coherent and efficient immune response. This implies a mediation by
      different soluble and/or membrane-anchored proteins related to innate immune
      receptors called PRRs (pattern-recognition receptors) to trigger immune signaling
      pathways. In most invertebrates, their roles have been inferred by analogy to
      those already characterized in vertebrate homologs. Despite the induction of
      their gene expression upon challenge and the presence of structural domains
      associated with the detection of pathogen-associated molecular patterns in their
      sequence, their exact role in the induction of immune response and their binding
      capacity still remain to be demonstrated. To this purpose, we developed a fast
      interactome approach, usable on any host-pathogen couple, to identify soluble
      proteins capable of directly or indirectly detecting the presence of pathogens.
      To investigate the molecular basis of immune recognition specificity, different
      pathogens (Gram-positive bacterium, Micrococcus luteus; Gram-negative,
      Escherichia coli; yeast, Saccharomyces cerevisiae; and metazoan parasites,
      Echinostoma caproni or Schistosoma mansoni) were exposed to hemocyte-free
      hemolymph from the gastropod Biomphalaria glabrata. Twenty-three different
      proteins bound to pathogens were identified and grouped into three different
      categories based on their primary function. Each pathogen was recognized by a
      specific but overlapping set of circulating proteins in mollusk's hemolymph.
      While known PRRs such as C-type lectins were identified, other proteins not known
      to be primarily involved in pathogen recognition were found, including actin,
      tubulin, collagen, and hemoglobin. Confocal microscopy and specific fluorescent
      labeling revealed that extracellular actin present in snail hemolymph was able to
      bind to yeasts and induce their clotting, a preliminary step for their
      elimination by the snail immune system. Aerolysin-like proteins (named
      biomphalysins) were the only ones involved in the recognition of all the five
      pathogens tested, suggesting a sentinel role of these horizontally acquired
      toxins. These findings highlight the diversity and complexity of a highly
      specific innate immune sensing system. It paves the way for the use of such
      approach on a wide range of host-pathogen systems to provide new insights into
      the specificity and diversity of immune recognition by innate immune systems.

PMID- 29051763
TI  - IL-12p35 Inhibits Neuroinflammation and Ameliorates Autoimmune Encephalomyelitis.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease in which
      cytokines produced by immune cells that infiltrate the brain and spinal cord play
      a central role. We show here that the IL-12p35, the alpha subunit of IL-12 or IL
      35 cytokine, might be an effective biologic for suppressing neuroinflammatory
      responses and ameliorating the pathology of experimental autoimmune
      encephalomyelitis (EAE), the mouse model of human MS. We further show that IL
      12p35 conferred protection from neuropathy by inhibiting the expansion of
      pathogenic Th17 and Th1 cells and inhibiting trafficking of inflammatory cells
      into the brain and spinal cord. In addition, in vitro exposure of
      encephalitogenic cells to IL-12p35 suppressed their capacity to induce EAE by
      adoptive transfer. Importantly, the IL-12p35-mediated expansion of Treg and Breg
      cells and its amelioration of EAE correlated with inhibition of cytokine-induced
      activation of STAT1/STAT3 pathways. Moreover, IL-12p35 inhibited lymphocyte
      proliferation by suppressing the expressions of cell-cycle regulatory proteins.
      Taken together, these results suggest that IL-12p35 can be exploited as a novel
      biologic for treating central nervous system autoimmune diseases and offers the
      promise of ex vivo production of large amounts of Tregs and Bregs for
      immunotherapy.

PMID- 29051764
TI  - Polyfunctional CD4+ T Cells As Targets for Tuberculosis Vaccination.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading
      cause of morbidity and mortality worldwide, despite the widespread use of the
      only licensed vaccine, Bacille Calmette Guerin (BCG). Eradication of TB will
      require a more effective vaccine, yet evaluation of new vaccine candidates is
      hampered by lack of defined correlates of protection. Animal and human studies of
      intracellular pathogens have extensively evaluated polyfunctional CD4+ T cells
      producing multiple pro-inflammatory cytokines (IFN-gamma, TNF-alpha, and IL-2) as
      a possible correlate of protection from infection and disease. In this study, we
      review the published literature that evaluates whether or not BCG and/or novel TB
      vaccine candidates induce polyfunctional CD4+ T cells and if these T cell
      responses correlate with vaccine-mediated protection. Ample evidence suggests
      that BCG and several novel vaccine candidates evaluated in animal models and
      humans induce polyfunctional CD4+ T cells. However, while a number of studies
      utilizing the mouse TB model support that polyfunctional CD4+ T cells are
      associated with vaccine-induced protection, other studies in mouse and human
      infants demonstrate no correlation between these T cell responses and protection.
      We conclude that induction of polyfunctional CD4+ T cells is certainly not
      sufficient and may not even be necessary to mediate protection and suggest that
      other functional attributes, such as additional effector functions, T cell
      differentiation state, tissue homing potential, or long-term survival capacity of
      the T cell may be equally or more important to promote protection. Thus, a
      correlate of protection for TB vaccine development remains elusive. Future
      studies should address polyfunctional CD4+ T cells within the context of more
      comprehensive immunological signatures of protection that include other functions
      and phenotypes of T cells as well as the full spectrum of immune cells and
      mediators that participate in the immune response against Mtb.

PMID- 29051765
TI  - Transcriptomic Analysis of Seed Coats in Yellow-Seeded Brassica napus Reveals
      Novel Genes That Influence Proanthocyanidin Biosynthesis.
AB  - Yellow seeds are a favorable trait for Brassica crops breeding due to better
      quality than their black-seeded counterparts. Here, we compared the Brassica
      napus seed coat transcriptomes between yellow- and brown-seeded near-isogenic
      lines (Y-NIL and B-NIL) that were developed from the resynthesized yellow-seeded
      line No. 2127-17. A total of 4,974 differentially expressed genes (DEG) were
      identified during seed development, involving 3,128 up-regulated and 1,835 down
      regulated genes in yellow seed coats. Phenylpropanoid and flavonoid biosynthesis
      pathways were enriched in down-regulated genes, whereas the top two pathways for
      up-regulated genes were plant-pathogen interaction and plant hormone signal
      transduction. Twelve biosynthetic genes and three regulatory genes involved in
      the flavonoid pathway exhibited similar expression patterns in seed coats during
      seed development, of which the down-regulation mainly contributed to the
      reduction of proanthocyanidins (PAs) in yellow seed coats, indicating that these
      genes associated with PA biosynthesis may be regulated by an unreported common
      regulator, possibly corresponding to the candidate for the dominant black-seeded
      gene D in the NILs. Three transcription factor (TF) genes, including one bHLH
      gene and two MYB-related genes that are located within the previous seed coat
      color quantitative trait locus (QTL) region on chromosome A09, also showed
      similar developmental expression patterns to the key PA biosynthetic genes and
      they might thus potentially involved participate in flavonoid biosynthesis
      regulation. Our study identified novel potential TFs involved in PAs accumulation
      and will provide pivotal information for identifying the candidate genes for seed
      coat color in B. napus.

PMID- 29051766
TI  - Overexpression of the Maize ZmNLP6 and ZmNLP8 Can Complement the Arabidopsis
      Nitrate Regulatory Mutant nlp7 by Restoring Nitrate Signaling and Assimilation.
AB  - Nitrate is a key nutrient that affects maize growth and yield, and much has yet
      to be learned about nitrate regulatory genes and mechanisms in maize. Here, we
      identified nine ZmNLP genes in maize and analyzed the functions of two ZmNLP
      members in nitrate signaling. qPCR results revealed a broad pattern of expression
      for ZmNLP genes in different stages and organs with the highest levels of
      transcript expression of ZmNLP6 and ZmNLP8. When ZmNLP6 and ZmNLP8 were
      overexpressed in the Arabidopsis nitrate regulatory gene mutant nlp7-4, nitrate
      assimilation and induction of nitrate-responsive genes in the transgenic plants
      were recovered to WT levels, indicating that ZmNLP6 and ZmNLP8 can replace the
      essential roles of the master nitrate regulatory gene AtNLP7 in nitrate signaling
      and metabolism. ZmNLP6 and ZmNLP8 are localized in the nucleus and can bind
      candidate nitrate-responsive cis-elements in vitro. The biomass and yield of
      transgenic Arabidopsis lines overexpressing ZmNLP6 and ZmNLP8 showed significant
      increase compared with WT and nlp7-4 mutant line in low nitrate conditions. Thus,
      ZmNLP6 and ZmNLP8 regulate nitrate signaling in transgenic Arabidopsis plants and
      may be potential candidates for improving nitrogen use efficiency of maize.

PMID- 29051767
TI  - Combined Effects of Irrigation Regime, Genotype, and Harvest Stage Determine
      Tomato Fruit Quality and Aptitude for Processing into Puree.
AB  - Industry tomatoes are produced under a range of climatic conditions and practices
      which significantly impact on main quality traits of harvested fruits. However,
      the quality of tomato intended for processing is currently addressed on delivery
      through color and Brix only, whereas other traits are overlooked. Very few works
      provided an integrated view of the management of tomato puree quality throughout
      the chain. To gain insights into pre- and post-harvest interactions, four
      genotypes, two water regimes, three maturity stages, and two processes were
      investigated. Field and glasshouse experiments were conducted near Avignon,
      France, from May to August 2016. Two irrigation regimes were applied: control
      plants were irrigated in order to match 100% of evapotranspiration (ETP); water
      deficit (WD) plants were irrigated as control plants until anthesis of the first
      flowers, then irrigation was reduced to 60 and 50% ETP in field, and glasshouse
      respectively. Fruits were collected at three stages during ripening. Their color,
      fresh weight, dry matter content, and metabolite contents were determined before
      processing. Pericarp cell size was evaluated in glasshouse only. Two laboratory
      scaled processing methods were applied before structural and biochemical analyses
      of the purees. Results outlined interactive effects between crop and process
      management. WD hardly reduced yield, but increased dry matter content in the
      field, in contrast to the glasshouse. The puree viscosity strongly depended on
      the genotype and the maturity stage, but it was disconnected from fruit dry
      matter content or Brix. The process impact on puree viscosity strongly depended
      on water supply during fruit production. Moreover, the lycopene content of fresh
      fruit may influence puree viscosity. This work opens new perspectives for
      managing puree quality in the field showing that it was possible to reduce water
      supply without affecting yield and to improve puree quality.

PMID- 29051768
TI  - Comparisons of Copy Number, Genomic Structure, and Conserved Motifs for alpha
      Amylase Genes from Barley, Rice, and Wheat.
AB  - Barley is an important crop for the production of malt and beer. However, crops
      such as rice and wheat are rarely used for malting. alpha-amylase is the key
      enzyme that degrades starch during malting. In this study, we compared the
      genomic properties, gene copies, and conserved promoter motifs of alpha-amylase
      genes in barley, rice, and wheat. In all three crops, alpha-amylase consists of
      four subfamilies designated amy1, amy2, amy3, and amy4. In wheat and barley,
      members of amy1 and amy2 genes are localized on chromosomes 6 and 7,
      respectively. In rice, members of amy1 genes are found on chromosomes 1 and 2,
      and amy2 genes on chromosome 6. The barley genome has six amy1 members and three
      amy2 members. The wheat B genome contains four amy1 members and three amy2
      members, while the rice genome has three amy1 members and one amy2 member. The B
      genome has mostly amy1 and amy2 members among the three wheat genomes. Amy1
      promoters from all three crop genomes contain a GA-responsive complex consisting
      of a GA-responsive element (CAATAAA), pyrimidine box (CCTTTT) and TATCCAT/C box.
      This study has shown that amy1 and amy2 from both wheat and barley have similar
      genomic properties, including exon/intron structures and GA-responsive elements
      on promoters, but these differ in rice. Like barley, wheat should have sufficient
      amy activity to degrade starch completely during malting. Other factors, such as
      high protein with haze issues and the lack of husk causing Lauting difficulty,
      may limit the use of wheat for brewing.

PMID- 29051769
TI  - OsGIF1 Positively Regulates the Sizes of Stems, Leaves, and Grains in Rice.
AB  - Growth-regulating factor (GRF) interacting factors (GIFs) are involved in several
      developmental processes in Arabidopsis. We previously showed that upregulation of
      OsGIF1 expression improves rice grain size. However, whether OsGIF1 is involved
      in other developmental processes remains unclear. Here, we report pleiotropic
      effects of OsGIF1 on rice organ size regulation. Overexpression and functional
      knock-out via a CRISPR/Cas9 strategy revealed that OsGIF1 not only positively
      regulates the sizes of rice leaf, stem, and grain but also influences rice
      reproduction. Expression profiles based on both qRT-PCR and GUS (beta
      glucuronidase) histochemical staining suggested that OsGIF1 is differentially
      expressed across various rice tissues, consistent with its roles in regulating
      the development of multiple rice organs. Additionally, we found that OsGIF1-GFP
      localized preferentially in the nucleus, which supports its proposed role as a
      transcriptional cofactor. Further histological analysis suggested that OsGIF1
      affected rice organ size possibly by regulating cell size. Our results suggest
      that OsGIF1 plays important roles in vegetative and reproductive developmental
      processes, with important implications for rice breeding.

PMID- 29051771
TI  - Prevalence, predictors and economic burden of morbidities among waste-pickers of
      Mumbai, India: a cross-sectional study.
AB  - BACKGROUND: The occupation of waste-picking characterised as 3Ds - dangerous,
      drudgery and demanding. In this context, the study aimed to assess occupational
      morbidities among the waste-pickers and attempts to identify potential individual
      level risk factors enhancing health risks. Additionally, economic burden of
      morbidities has been assessed. METHODS: The burden of the morbidities was
      assessed and compared with a comparison group through a cross-sectional survey.
      Waste-pickers (n = 200) and a comparison group (n = 103) working for at least a
      year were randomly selected from the communities living on the edge of the Deonar
      dumping site. The difference in the prevalence of morbidities was tested using
      the chi-square test. The effect of waste picking resulting the development of
      morbidities was assessed using the propensity score matching (PSM) method. A
      multivariate logistic regression model was employed to identify the individual
      risk factors. T-test has been employed in order to analyse the difference in
      health care expenditure between waste pickers and non-waste pickers. RESULTS: The
      prevalence of morbidities was significantly higher among the waste-pickers,
      particularly for injuries (75%), respiratory illness (28%), eye infection (29%),
      and stomach problems (32%), compared to the comparison group (17%, 15%, 18%, and
      19% respectively). The results of the PSM method highlighted that waste-picking
      raised the risk of morbidity for injuries (62%) and respiratory illness (13%).
      Results of logistic regression suggest that low level of hygiene practices
      [household cleanliness (OR = 3.23, p < 0.00), non-use of soap before meals (OR =
      2.65, p < 0.05)] and use of recyclable items as a cooking fuel (OR = 2.12, p <
      0.03) enhanced health risks among the waste pickers when adjusted for the age,
      duration of work, duration of stay in community and substance use. Additionally,
      the high prevalence of morbidities among waste pickers resulted into higher
      healthcare expenditure. Findings of the study suggest that not only healthcare
      expenditure but persistence of illness and work days lost due to injury/illness
      is significantly higher among waste pickers compared to non-waste pickers.
      CONCLUSIONS: The study concluded that waste-picking raised the risk of
      morbidities as also expenditure on healthcare. Results from the study recommend
      several measures to lessen the morbidities and thereby incurred healthcare
      expenditure.

PMID- 29051772
TI  - Hyperspectral image analysis techniques for the detection and classification of
      the early onset of plant disease and stress.
AB  - This review explores how imaging techniques are being developed with a focus on
      deployment for crop monitoring methods. Imaging applications are discussed in
      relation to both field and glasshouse-based plants, and techniques are sectioned
      into 'healthy and diseased plant classification' with an emphasis on
      classification accuracy, early detection of stress, and disease severity. A
      central focus of the review is the use of hyperspectral imaging and how this is
      being utilised to find additional information about plant health, and the ability
      to predict onset of disease. A summary of techniques used to detect biotic and
      abiotic stress in plants is presented, including the level of accuracy associated
      with each method.

PMID- 29051770
TI  - Serum alanine aminotransferase/aspartate aminotransferase ratio is one of the
      best markers of insulin resistance in the Chinese population.
AB  - BACKGROUND: The alanine aminotransferase (ALT)/aspartate aminotransferase (AST)
      ratio is reportedly associated with insulin resistance (IR). However, few studies
      have explored the relationship between the ALT/AST ratio and IR in the Chinese
      population. Here, we aimed to explore whether the ALT/AST ratio is associated
      and, if so, to what extent, with IR in the Chinese population as categorized by
      waist circumference (WC). METHODS: Our data were obtained from the SPECT-China
      study, a cross-sectional survey on the prevalence of metabolic diseases and risk
      factors in East China from 2014 to 2015. A total of 8398 participants aged 52.16
      +/- 13.16 (mean +/- standard deviation) years were included in this study.
      Anthropometric indices, biochemical parameters and clinical characteristics were
      measured. IR was defined as the top quartile of the homeostasis model assessment
      of insulin resistance (HOMA-IR > 1.6), and central obesity was defined as a WC
      >=90 cm in males or >=80 cm in females. Linear regression and receiver operating
      characteristic curve analyses were conducted. RESULTS: The ALT/AST ratio was
      significantly correlated and associated with HOMA-IR in both non-centrally obese
      (r = 0.284, B = 0.509, 95% confidence interval (CI): 0.459-0.559, P < 0.001) and
      centrally obese subjects (r = 0.372, B = 0.607, 95%CI: 0.532-0.683, P < 0.001)
      after adjusting for potential confounders. The ALT/AST ratio was one of the best
      markers of IR, with areas under the curve (AUC) values of 0.66 (0.64-0.68) in non
      centrally and 0.68 (0.66-0.70) in centrally obese subjects. In the prediction
      model for IR, the AUCs were significantly augmented after adding the ALT/AST
      ratio in both non-centrally obese [AUC 95%CI 0.69(0.67-0.71) vs 0.72(0.70-0.74),
      P<0.001] and central obese [AUC 95%CI 0.69(0.67-0.71) vs 0.73(0.72-0.75),
      P<0.001] subjects. The optimal cut-off points of the ALT/AST ratio for
      identifying IR were 0.80 in non-centrally obese people and 0.78 in centrally
      obese people, respectively. CONCLUSION: The ALT/AST ratio may be one of the best
      markers for IR in the Chinese population. Whether the ALT/AST ratio should be
      regarded as an additional metabolic syndrome component in the Chinese population
      warrants further investigation.

PMID- 29051773
TI  - An improved microscale method for extraction of phenolic acids from maize.
AB  - BACKGROUND: Phenolic acids are a major group of secondary metabolites widely
      distributed in plants. In the case of maize, the major proportion of these
      metabolites occurs in the edible grain and their antioxidant activities are
      associated with improvements in human health. However, conventional extraction of
      secondary metabolites is very time consuming and generates a substantial amount
      of solvent waste. One approach to resolve these limitations is the use of
      microscale approaches, which minimize the quantity of solvents required, as well
      as the sample amounts and processing times. The objective of this work was to
      develop an improved microscale method for extraction of phenolic acids from maize
      and to compare it with a conventional extraction method. RESULTS: The improved
      microscale extraction method, coupled with an HPLC-DAD detection method, allowed
      identification of ferulic acid, p-coumaric acid in its free and bound form, and
      some diferulic acids. In its free form, p-coumaric acid ranged in content from
      2.4 to 6.5 ug/g dry weight (dw) using the conventional method and 7.7 to 54.8
      ug/g dw using the improved microscale method. Free ferulic acid content ranged
      from 2.6 to 12.9 ug/g dw for the conventional method and 16.8 to 181.7 ug/g dw
      for the improved microscale method. In its bound form, p-coumaric acid ranged in
      content from 6.0 to 30.6 ug/g dw for the traditional method and 34.4 to 138.6
      ug/g dw for the improved microscale method. Bound ferulic acid ranged from 131.8
      to 427.5 ug/g dw for the conventional method and 673.8 to 1702.7 ug/g dw for the
      improved microscale method. The coefficient of variation associated was lower for
      the improved microscale method than for the conventional method, thereby assuring
      the replicability of the process. CONCLUSIONS: The improved microscale method
      proposed here increases the extraction power and batch capacity, while reducing
      the sample quantity, solvent amounts and extraction time. It also achieves a
      better replicability with a lower coefficient of variation than is possible with
      conventional extraction.

PMID- 29051775
TI  - Obstetric Medicine and social media: Friend or foe?

PMID- 29051774
TI  - Effectiveness of the BOOST-ATM online transition planning program for adolescents
      on the autism spectrum: a quasi-randomized controlled trial.
AB  - BACKGROUND: The majority of existing transition planning programs are focused on
      people with a disability in general and may not meet the specific need of
      adolescents on the autism spectrum. In addition, these interventions focus on
      specific skills (e.g. job readiness or self-determination) rather than the
      overall transition planning process and there are methodological limitations to
      many of the studies determining their effectiveness. The Better OutcOmes &
      Successful Transitions for Autism (BOOST-ATM) is an online program that supports
      adolescents on the autism spectrum to prepare for leaving school. This study
      aimed to determine the effectiveness of the BOOST-ATM in enhancing self
      determination. METHODS: A quasi-randomized controlled trial was conducted with
      adolescents on the autism spectrum enrolled in years 8 to 11 in Australian
      schools (N = 94). Participants had to have basic computer skills and the ability
      to write at a year 5 reading level. Participants were allocated to a control (n =
      45) or intervention (n = 49) group and participants were blinded to the trial
      hypothesis. The intervention group used the BOOST-ATM for 12 months, while the
      control group participated in regular practice. Outcomes included self
      determination, career planning and exploration, quality of life, environmental
      support and domain specific self-determination. Data were collected from parents
      and adolescents. RESULTS: There were no significant differences in overall self
      determination between groups. Results indicated significant differences in favor
      of the intervention group in three areas: opportunity for self-determination at
      home as reported by parents; career exploration as reported by parents and
      adolescents; and transition-specific self-determination as reported by parents.
      CONCLUSIONS: Results provide preliminary evidence that the BOOST-ATM can enhance
      some career-readiness outcomes. Lack of significant outcomes related to self
      determination at school and career planning may be due to the lack of face-to
      face training and parents being the primary contacts in the study. Further
      research is needed to determine effectiveness of the BOOST-ATM related to post
      secondary education and employment. Trial registration #ACTRN12615000119594.

PMID- 29051776
TI  - Fontan circulation and implications for future reproduction.
AB  - This article summarizes and critiques four recent publications looking at
      preconception counseling, pregnancy outcomes, and cardiac complications in women
      with history of Fontan circulation. The Fontan procedure is a palliative strategy
      for single-ventricle type congenital heart disease and involves passive flow of
      venous return into the pulmonary circulation, bypassing the ventricles. Pregnancy
      in these patients is not without risk and preconception counseling and
      contraception practices vary widely. High rates of miscarriage, prematurity, and
      small-for-gestational-age babies are reported. Cardiac complications include
      mainly arrhythmias. Whether long-term prognosis in these patients is affected by
      pregnancy is not yet known.

PMID- 29051777
TI  - Melanoma in pregnancy.
AB  - Melanoma is one of the most common cancers diagnosed in pregnancy and has a high
      metastatic potential. As the incidence of melanoma increases, careful clinical
      evaluation of suspicious skin lesions remains the mainstay of early diagnosis.
      There is controversy in the literature as to whether pregnancy-associated
      melanoma has worse survival than other melanomas. Any changing-pigmented lesion
      should be biopsied, regardless of pregnancy hyperpigmentation. Increased
      lymphangiogenesis in pregnancy is associated with increased metastasis - timely
      diagnosis is therefore imperative. While the effect of oestrogen and progesterone
      on melanoma is under investigation, it is generally accepted that oral
      contraceptive use in not contraindicated after a diagnosis of melanoma in
      pregnancy. Subsequent pregnancy should be delayed for two to three years after a
      diagnosis of melanoma with a high risk of recurrence.

PMID- 29051778
TI  - Reverse innovation in maternal health.
AB  - Reverse innovation, defined as the flow of ideas from low- to high-income
      settings, is gaining traction in healthcare. With an increasing focus on value,
      investing in low-cost but effective and innovative solutions can be of mutual
      benefit to both high- and low-income countries. Reverse innovation has a role in
      addressing maternal health challenges in high-income countries by harnessing
      these innovative solutions for vulnerable populations especially in rural and
      remote regions. In this paper, we present three examples of 'reverse innovation'
      for maternal health: a low-cost, easy-to-use blood pressure device (CRADLE), a
      diagnostic algorithm (mini PIERS) and accompanying mobile app (PIERS on the
      Move), and a novel method for mapping maternal outcomes (MOM).

PMID- 29051779
TI  - Childhood maltreatment and inflammation among pregnant women with gestational
      diabetes mellitus: A pilot study.
AB  - BACKGROUND: Women with childhood maltreatment histories are at increased risk for
      adverse birth outcomes. Mechanisms explaining this link are poorly understood.
      Past research is limited by sampling pregnant women at low risk for adverse
      maternal and neonatal outcomes. METHODS: This pilot study was a secondary data
      analysis of 24 women with gestational diabetes mellitus; 17% of the sample also
      reported a maltreatment history. Women provided a blood sample to measure
      inflammatory cytokines and insulin resistance, and saliva samples to measure
      diurnal cortisol. Birth outcomes for past and current pregnancies were recorded.
      RESULTS: Histories of maltreatment were associated with elevated interleukin-15
      and a marginally greater incidence of preterm delivery in current and past
      pregnancies. CONCLUSIONS: This pilot study was the first to demonstrate an
      association between childhood maltreatment history and inflammatory cytokine
      levels in pregnant women diagnosed with gestational diabetes mellitus.

PMID- 29051780
TI  - Sensitivity of postnatal fasting plasma glucose in identifying impaired glucose
      tolerance in women with gestational diabetes - 25 Years' data.
AB  - OBJECTIVE: To assess the uptake of postnatal oral glucose tolerance test and to
      determine the sensitivity of fasting postnatal blood sugar in predicting 2-h
      impaired glucose tolerance. METHODS: Retrospective study of 1961 women diagnosed
      with gestational diabetes mellitus. All women were offered oral glucose tolerance
      test six weeks post-delivery. RESULTS: Of 1961 women, 1090 (56%) returned for
      postpartum oral glucose tolerance test. A fasting plasma glucose of >=6.1 mmol/l
      identified only 76 of 167 women with impaired glucose tolerance detected by a 2-h
      oral glucose tolerance test (sensitivity of 45.5%; 95%CI: 38.1-53.1). We observed
      a normal fasting glucose but an impaired 2-h glucose tolerance in 91 out of 968
      (9.4%) women. Asian ethnicity, admission on special care baby unit and antenatal
      insulin therapy strongly predicted 2-h impaired postnatal blood glucose levels (P
      < 0.05). CONCLUSION: Although fasting plasma glucose is a convenient method, it
      lacks sensitivity in identifying women with impaired glucose tolerance
      postnatally.

PMID- 29051781
TI  - Prediction of adverse pregnancy outcomes by extreme values of first trimester
      screening markers.
AB  - BACKGROUND: To determine the association between extreme values of first
      trimester markers and adverse pregnancy outcomes. METHODS: A retrospective cohort
      study of 916 women who underwent first-trimester combined screening during 2015
      was performed. Extreme values of NT, pregnancy-associated plasma protein-A (PAPP
      A) and free beta-hCG, and their association with adverse pregnancy outcomes were
      analyzed. RESULTS: Low PAPP-A (<10th percentile) was associated with an increased
      risk for preeclampsia (adjusted odds ratio (AOR) 4.13), fetal growth restriction
      (AOR 3.94) and abruptio placentae (AOR 52.63). Abnormally low or high free beta
      hCG, high PAPP-A or increased NT was not associated with an increased risk for
      adverse outcomes. DISCUSSION: PAPP-A <10th percentile could be associated with an
      increased risk for adverse outcomes. However, the majority of patients with these
      events do not have abnormal PAPP-A and few patients with PAPP-A <10th percentile
      will have an adverse outcome.

PMID- 29051782
TI  - Management of uncommon disorders in pregnancy: Von Hippel-Lindau disease,
      Gitelman syndrome, and Nutcracker syndrome.
AB  - Uncommon renal disorders in pregnancy can be challenging to manage given limited
      evidence in the literature to guide management. We present a series of three
      uncommon renal disorders in pregnancy: Von Hippel-Lindau disease, Gitelman
      syndrome, and Nutcracker syndrome. Previously published case reports with
      differing outcomes offer some guidance to the management of these disorders in
      pregnancy. In this case series, we address the management of these syndromes
      during pregnancy and discuss the maternal and fetal outcomes. All three of our
      patients had good maternal and fetal outcomes, which will contribute to current
      data on maternal and fetal outcomes in these rare diseases, which is limited.

PMID- 29051783
TI  - A case of pulmonary carcinoid in pregnancy and review of carcinoid tumours in
      pregnancy.
AB  - Carcinoid tumours are rare slow growing tumours which arise from primitive
      neuroendocrine cells. The effect of the pregnant state on carcinoid tumours and
      vice versa remains unclear, as does the optimal management of carcinoid tumours
      during the pregnancy including labour. We report the rare case of a 36 year old
      primigravida woman with large bilateral pulmonary carcinoid tumours. The
      patient's disease was minimally symptomatic with no clinical suspicion of
      carcinoid syndrome. Under close observation, the pregnancy progressed well and
      the patient proceeded to a spontaneous vaginal delivery of a healthy child. We
      conduct the the first literature review in 30 years of all reported cases in this
      area and make suggestions as to assessment and monitoring of cases of carcinoid
      during pregnancy.

PMID- 29051784
TI  - Delivery and postpartum management of a patient with Pompe disease: Case report
      and review of the literature.
AB  - Pompe disease is an autosomal-recessive disorder caused by acid alpha-glucosidase
      deficiency due to mutations in the GAA gene. There are two forms of the disease:
      infantile-onset Pompe disease and late-onset Pompe disease. The worldwide
      incidence of both forms of the disease is commonly reported to be 1 in 40,000.
      Adult patients are affected by limb-girdle muscular weakness and respiratory
      insufficiency. Enzyme replacement therapy with alglucosidase-alpha is available
      since 2006. There is little knowledge about pregnant woman with Pompe disease.
      These women should be considered as high-risk pregnant women. Here, we aim to
      present Cesarean delivery and postpartum management of a case with an interrupted
      enzyme replacement therapy during pregnancy.

PMID- 29051785
TI  - Pediatric injury information seeking for mothers with young children: The role of
      health literacy and ehealth literacy.
AB  - BACKGROUND: An understanding of preferred sources of injury information among
      parents is needed to develop best practices for information dissemination. Yet,
      almost no research examines injury information seeking for a national sample of
      mothers. METHODS: A cross-sectional online survey was conducted in 2013 with 1081
      mothers in the United States (U.S.) with at least one child <6 years. We measured
      self-report health literacy with the Morris Single-Item Screener (18% low), and
      eHealth literacy using the eHEALS (28% low). RESULTS: The internet was the most
      preferred source for injury information (76%), followed by health providers
      (44%), and family/friends (35%). Most mothers selected the internet as the first
      choice for information about bicycle helmets (65%) and car seats (63%). For
      poison prevention, preferences were mixed; 48% internet compared with 41% health
      providers. Mothers with low health literacy were more likely to have discussed
      injury prevention with their doctors (P = 0.022) and searched for injury
      information (P = 0.001), but less likely to report the internet as a top source
      (P < .0001). Mothers with low eHealth literacy were less likely to search for
      injury information (P < 0.0001) and report the internet as a top source (P <
      0.0001), and slightly more likely to rely on health providers for information (P
      = 0.028). CONCLUSIONS: Findings suggest the internet is a common source of injury
      prevention information, but health providers remain a valuable resource for
      mothers, especially those with lower literacy skills. Despite widespread internet
      use, health providers should be sure to communicate injury prevention information
      to mothers, especially those at risk for low health literacy and eHealth
      literacy.

PMID- 29051786
TI  - The prognostic value of histology in ulcerative colitis in clinical remission
      with mesalazine.
AB  - BACKGROUND: The aim of the study was to compare the prognostic value of
      histological and endoscopic activity in patients with ulcerative colitis (UC).
      METHODS: Patients in clinical remission for 1 year under treatment with
      mesalazine underwent a planned colonoscopy with biopsies. Histological activity
      was scored using the histological activity index (HAI). Endoscopic activity was
      scored using the Mayo endoscopic subscore (MES). The clinical course was
      evaluated measuring relapses needing steroids during a follow up of 3 years.
      RESULTS: A total of 52 patients were enrolled into the study and followed up for
      3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17
      patients (32.69%) showed no histological alteration. At 3 years of follow up,
      overall, 26 patients (50%) were still in steroid-free remission. Using univariate
      logistic regression analysis, both histological (HAI ? 1) and endoscopic activity
      (MES ? 1) were significantly associated with outcome, showing, respectively, a
      relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI
      0) (96% confidence interval [CI]: 3.2-84.3) and 6.3 times higher with respect to
      endoscopic remission (MES 0) (96% CI: 1.9-21.3). After multivariate logistic
      regression analysis, histological activity was the only factor significantly
      associated with outcome (OR 10.2; 95% CI: 1.7-59.4). CONCLUSIONS: Histological
      activity has the most powerful prognostic value in predicting the need for
      steroids in patients with UC in stable clinical remission on mesalazine. It could
      be considered as a target of therapy in UC.

PMID- 29051787
TI  - Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter
      2 indicates a poor prognosis in hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4alpha) plays an important role
      in tumourigenesis. There is growing evidence indicating that HNF4alpha
      transcribed by promoter 1 (P1-HNF4alpha) is expressed at relatively low levels in
      HCC and its presence predicts a favourable outcome for hepatocellular carcinoma
      (HCC) patients. However, the role of HNF4alpha transcribed by promoter 2 (P2
      HNF4alpha) in HCC remains unclear. METHODS: A total of 615 HCC specimens were
      obtained to construct tissue microarrays and perform immunohistochemistry. The
      relationship between P2-HNF4alpha and clinical features of HCC patients were
      analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of
      P2-HNF4alpha. RESULTS: The results showed that the expression of P2-HNF4alpha in
      HCC was noticeably increased in HCC tissues compared with the nontumourous
      tissues. In addition, P1-HNF4alpha expression was negatively correlated with P2
      HNF4alpha expression (p = 0.023). High P2-HNF4alpha expression was significantly
      associated with poor differentiation of HCC (p = 0.002) and vascular invasion (p
      = 0.017). Kaplan-Meier analysis showed that P2-HNF4alpha expression was closely
      correlated with overall survival in the training group (p = 0.01), validation
      group (p = 0.034), and overall group of patients with HCC (p < 0.001).
      CONCLUSIONS: Our data show that the role of HNF4alpha in cancer development needs
      to be further refined. P2-HNF4alpha, different from P1-HNF4alpha, is markedly
      upregulated and serves as an oncogene-associated protein in HCC. Our study
      therefore provides a promising biomarker for prognostic prediction and a
      potential therapeutic target for HCC.

PMID- 29051788
TI  - Emerging oral targeted therapies in inflammatory bowel diseases: opportunities
      and challenges.
AB  - To improve quality of life and prevent long-term risks in patients with
      inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is
      essential to suppress inflammatory activity adequately. However, corticosteroids
      are only suitable for therapy of acute flares and the evidence for positive
      effects of immunosuppressive substances like azathioprine or 6-mercapropurine is
      mainly limited to maintenance of remission. In addition, only subgroups of
      patients benefit from biologicals targeting tumour necrosis factor alpha or
      alpha4beta7 integrins. In summary, until now the disease activity is not
      sufficiently controlled in a relevant fraction of the patients with IBD. Thus,
      there is an urge for the development of new substances in the therapy of
      ulcerative colitis and Crohn's disease. Fortunately, new oral and parenteral
      substances are in the pipeline. This review will focus on oral substances, which
      have already passed phase II studies successfully at this stage. In this article,
      we summarize data regarding AJM300, phosphatidylcholine (LT-02), mongersen,
      ozanimod, filgotinib and tofacitinib. AJM300 and ozanimod were tested in patients
      with ulcerative colitis and target lymphocyte trafficking through inhibition of
      the alpha subunit of integrin, respectively binding to the sphingosine-1
      phosphate receptor (subtypes 1 and 5) on lymphocytes. Mongersen was utilized in
      patients with Crohn's disease and accelerates the degradation of SMAD7 mRNA,
      which consequently strengthens the mainly anti-inflammatory signalling pathway of
      transforming growth factor beta1. Various Janus kinase (JAK) inhibitors were
      developed, which inhibit the intracellular signalling pathway of cytokines. For
      example, the JAK1 blocker filgotinib was tested in Crohn's disease, whereas the
      JAK1/3 inhibitor tofacitinib was tested in clinical trials for both Crohn's
      disease and ulcerative colitis. A different therapeutic approach is the
      substitution of phosphatidylcholine (LT-02), which might recover the colonic
      mucus. Taken together, clinical trials with these new agents have opened avenues
      for further clinical studies and it can be expected that at least some of these
      agents will be finally approved for clinical therapy.

PMID- 29051789
TI  - Novel strategies and therapeutic options for the management of primary biliary
      cholangitis.
AB  - Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. It has a
      varied course of progression ranging from being completely asymptomatic to
      aggressive disease leading to cirrhosis and resulting in liver transplantation.
      In addition, symptoms can be debilitating and can have a major impact on quality
      of life. For decades, there was only one anti-cholestatic agent available to
      target this disease and that was only effective in around half of patients, with
      little or no effect on symptoms. With increasing understanding of the pathogenic
      mechanisms of PBC and potential targets for drug treatment, pharmaceutical
      companies have shown a greater interest in this rare disease. A large number of
      novel therapeutic molecules have been developed and are currently being
      evaluated. In this review article all the novel molecules in use and in trials
      targeting cholestasis and symptoms in PBC are discussed.

PMID- 29051790
TI  - Current immunotherapeutic strategies in hepatocellular carcinoma: recent advances
      and future directions.
AB  - Hepatocellular carcinoma (HCC) is a common and serious health problem with high
      mortality. Treatment for HCC remains largely unsatisfactory owing to its high
      recurrence rates and frequent accompanying cirrhosis. In addition, the unique
      immune environment of the liver promotes tolerance, which, in conjunction with
      immune evasion by the disease, makes HCC a less promising target for conventional
      immunotherapy. However, recent advances in the immunotherapy have led to novel
      approaches to overcome these obstacles by manipulating and enhancing tumor
      specific immune responses against HCC by using various modalities, such as cancer
      vaccines and immune checkpoint blockade. These treatments have shown both safety
      and promising outcomes in patients with HCC of various etiologies and tumor
      stages. Furthermore, combined strategies have been assessed to achieve optimal
      outcomes, by using immunotherapies with or without conventional treatments. This
      review briefly covers the background, recent advances, current issues, and future
      perspectives on immunotherapy in the field of HCC treatment.

PMID- 29051791
TI  - Hyalinizing trabecular tumor of the thyroid gland and its significant diagnostic
      issue.
AB  - BACKGROUND: Hyalinizing trabecular tumors (HTT) are rare follicular cell-derived
      tumors of the thyroid gland that are infrequently reported in otolaryngology
      literature. We present here an interesting case of HTT which provides the basis
      for review of this entity's clinical characteristics, criteria useful in making
      the diagnosis, and any currently available therapeutic modalities. CASE
      PRESENTATION: A 70-year-old Caucasian female underwent a CT scan of her chest and
      was incidentally found to have a nodule within the right thyroid lobe. Gross
      examination of the excised thyroid lobe revealed a circumscribed and encapsulated
      lesion (tan / gritty in texture), confined to the gland. Histologic sections of
      the lesion revealed a circumscribed neoplasm with a trabecular and organoid
      architecture associated with abundant dystrophic calcification. Neoplastic cells
      showed a spindled morphology with clumped chromatin and ample eosinophilic
      cytoplasm. CONCLUSIONS: Histologically, HTT is a follicular cell-derived tumor
      composed of neoplastic cells arranged in a trabecular pattern with hyalinization
      and calcification of extracellular material. Distinguishing features of HTT
      include minimal cytologic atypia with a low nuclear: cytoplasmic ratio, cellular
      aggregates around hyalinized material, and nuclei with clumped chromatin and
      occasional grooves and/or pseudoinclusions. Though debated in the literature, the
      general consensus is that this tumor is a benign entity. It is our hope that
      additional clinical research will elicit awareness of these rare tumors.

PMID- 29051792
TI  - Papillary thyroid cancer recurrence 43 Years following Total Thyroidectomy and
      radioactive iodine ablation: a case report.
AB  - BACKGROUND: Recurrent papillary thyroid carcinoma (PTC) beyond the first two
      decades of definitive treatment (i.e. total thyroidectomy and radioactive iodine
      ablation) is a rare occurrence. CASE PRESENTATION: We present a case of a 71-year
      old Caucasian female with a distant history of PTC treated with total
      thyroidectomy and radioactive iodine ablation who experienced recurrence of her
      disease 43 years following initial diagnosis and definitive treatment. She
      presented with palpable left-sided neck mass and subsequently underwent a level
      II, III, neck dissection and adjuvant iodine ablation. This case presents the
      latest recurrence in papillary thyroid cancer documented to date in the
      literature. CONCLUSION: This case exemplifies the need for the head and neck
      surgeon, radiation oncologist, general practitioner and radiologist to consider
      new lateral neck mass as late-presenting recurrence of PTC until proven otherwise
      regardless of low recurrence rates beyond two decades from treatment and low
      prognostic risk scores.

PMID- 29051793
TI  - Multiplexed Detection of MicroRNA Biomarkers Using SERS-Based Inverse Molecular
      Sentinel (iMS) Nanoprobes.
AB  - MicroRNAs (miRNAs) have demonstrated great promise as a novel class of biomarkers
      for early detection of various cancers, including breast cancer. However, due to
      technical difficulties in detecting these small molecules, miRNAs have not been
      adopted into routine clinical practice for early diagnostics. Thus, it is
      important to develop alternative detection strategies that could offer more
      advantages over conventional methods. Here, we demonstrate the application of a
      "turn-on" SERS sensing technology, referred to as "inverse Molecular Sentinel
      (iMS)" nanoprobes, as a homogeneous assay for multiplexed detection of miRNAs.
      This SERS nanoprobe involves the use of plasmonic-active nanostars as the sensing
      platform. The "OFF-to-ON" signal switch is based on a nonenzymatic strand
      displacement process and the conformational change of stem-loop (hairpin)
      oligonucleotide probes upon target binding. This technique was previously used to
      detect a synthetic DNA sequence of interest. In this study, we modified the
      design of the nanoprobe to be used for the detection of short (22-nt) miRNA
      sequences. The demonstration of using iMS nanoprobes to detect miRNAs in real
      biological samples was performed with total small RNA extracted from breast
      cancer cell lines. The multiplex capability of the iMS technique was demonstrated
      using a mixture of the two differently labeled nanoprobes to detect miR-21 and
      miR-34a miRNA biomarkers for breast cancer. The results of this study demonstrate
      the feasibility of applying the iMS technique for multiplexed detection of short
      miRNAs molecules.

PMID- 29051794
TI  - Electronic Structure of the [Cu3(MU-O)3]2+ Cluster in Mordenite Zeolite and Its
      Effects on the Methane to Methanol Oxidation.
AB  - Identifying Cu-exchanged zeolites able to activate C-H bonds and selectively
      convert methane to methanol is a challenge in the field of biomimetic
      heterogeneous catalysis. Recent experiments point to the importance of trinuclear
      [Cu3(MU-O)3]2+ complexes inside the micropores of mordenite (MOR) zeolite for
      selective oxo-functionalization of methane. The electronic structures of these
      species, namely, the oxidation state of Cu ions and the reactive character of the
      oxygen centers, are not yet fully understood. In this study, we performed a
      detailed analysis of the electronic structure of the [Cu3(MU-O)3]2+ site using
      multiconfigurational wave-function-based methods and density functional theory.
      The calculations reveal that all Cu sites in the cluster are predominantly
      present in the Cu(II) formal oxidation state with a minor contribution from
      Cu(III), whereas two out of three oxygen anions possess a radical character.
      These electronic properties, along with the high accessibility of the out-of
      plane oxygen center, make this oxygen the preferred site for the homolytic C-H
      activation of methane by [Cu3(MU-O)3]2+. These new insights aid in the
      construction of a theoretical framework for the design of novel catalysts for
      oxyfunctionalization of natural gas and suggest further spectroscopic
      examination.

PMID- 29051795
TI  - Criminogenic Needs, Substance Use, and Offending among Rural Stimulant Users.
AB  - There is a need to understand the determinants of both substance use and criminal
      activity in rural areas in order to design appropriate treatment interventions
      for these linked problems. The present study drew on a predominant model used to
      assess and treat offenders -- the Risk-Need-Responsivity (RNR) model -- to
      examine risk factors for substance use and criminal activity in a rural drug
      using sample. This study extends the RNR model's focus on offenders to assessing
      rural-dwelling individuals using stimulants (N=462). We examined substance use
      and criminal justice outcomes at 6-month (91%) and 3-year (79%) follow-ups, and
      used Generalized Estimating Equations to examine the extent to which RNR
      criminogenic need factors at baseline predicted outcomes at follow-ups. Substance
      use and criminal justice outcomes improved at six months, and even more at three
      years, post-baseline. As expected, higher risk was associated with poorer
      outcomes. Antisocial personality patterns and procriminal attitudes at baseline
      predicted poorer legal and drug outcomes measured at subsequent follow-ups. In
      contrast, less connection to antisocial others and fewer work difficulties
      predicted lower alcohol problem severity, but more frequent alcohol use.
      Engagement in social-recreational activities was associated with fewer subsequent
      arrests and less severe alcohol and drug problems. The RNR model's criminogenic
      need factors predicted drug use and crime-related outcomes among rural residents.
      Services adapted to rural settings that target these factors, such as telehealth
      and other technology-based resources, may hasten improvement on both types of
      outcomes among drug users.

PMID- 29051796
TI  - ACTIVE MEAN FIELDS FOR PROBABILISTIC IMAGE SEGMENTATION: CONNECTIONS WITH CHAN
      VESE AND RUDIN-OSHER-FATEMI MODELS.
AB  - Segmentation is a fundamental task for extracting semantically meaningful regions
      from an image. The goal of segmentation algorithms is to accurately assign object
      labels to each image location. However, image-noise, shortcomings of algorithms,
      and image ambiguities cause uncertainty in label assignment. Estimating the
      uncertainty in label assignment is important in multiple application domains,
      such as segmenting tumors from medical images for radiation treatment planning.
      One way to estimate these uncertainties is through the computation of posteriors
      of Bayesian models, which is computationally prohibitive for many practical
      applications. On the other hand, most computationally efficient methods fail to
      estimate label uncertainty. We therefore propose in this paper the Active Mean
      Fields (AMF) approach, a technique based on Bayesian modeling that uses a mean
      field approximation to efficiently compute a segmentation and its corresponding
      uncertainty. Based on a variational formulation, the resulting convex model
      combines any label-likelihood measure with a prior on the length of the
      segmentation boundary. A specific implementation of that model is the Chan-Vese
      segmentation model (CV), in which the binary segmentation task is defined by a
      Gaussian likelihood and a prior regularizing the length of the segmentation
      boundary. Furthermore, the Euler-Lagrange equations derived from the AMF model
      are equivalent to those of the popular Rudin-Osher-Fatemi (ROF) model for image
      denoising. Solutions to the AMF model can thus be implemented by directly
      utilizing highly-efficient ROF solvers on log-likelihood ratio fields. We
      qualitatively assess the approach on synthetic data as well as on real natural
      and medical images. For a quantitative evaluation, we apply our approach to the
      icgbench dataset.

PMID- 29051797
TI  - Optimal Design of Wavelength Selective Thermal Emitter for Thermophotovoltaic
      Applications.
AB  - We theoretically and numerically demonstrate optimal design of wavelength
      selective thermal emitter using one-dimensional (1D) and two-dimensional (2D)
      metal-dielectric gratings for thermophotovoltaic (TPV) applications. Proposed
      design consists of tungsten (W) and silicon dioxide (SiO2) gratings which can
      withstand high temperatures. Radiative properties of 1D grating were calculated
      using a numerical method, while effective medium approximation was used for 2D
      gratings. Optimal designs were obtained such that output power is maximum for
      GaSb photovoltaic (PV) cell at emitter temperature of 1500 K and radiated energy
      for longer wavelengths is limited to a low value. A constrained optimization was
      performed using genetic algorithm (GA) to arrive at optimal design.

PMID- 29051798
TI  - Perceptions of Climate Change, Sea Level Rise, and Possible Consequences Relate
      Mainly to Self-Valuation of Science Knowledge.
AB  - This study examines perceptions of climate change and sea level rise in New
      Jersey residents in 2012 and 2014. Different surveys have shown declines in
      interest and concern about climate change and sea level rise. Climate change and
      increasing temperatures have an anthropogenic cause, which relates to energy use,
      making it important to examine whether people believe that it is occurring. In
      late 2012 New Jersey experienced Super storm Sandy, one of the worst hurricanes
      in its history, followed by public discussion and media coverage of stronger more
      frequent storms due to climate change. Using structured interviews, we tested the
      null hypotheses that there were no differences in perceptions of 1260
      interviewees as a function of year of the survey, age, gender, years of
      education, and self-evaluation of science knowledge (on a scale of 1 to 5). In
      2012 460 of 639 (72%) rated "global warming occurring" as "certain" (#4) or "very
      certain" (#5) compared with 453 of 621 (73%) in 2014. For "due to human
      activities" the numbers of "certain" or "very certain" were 71% in 2012, and 67%
      in 2014 and for sea level rise the numbers were 64% and 70%. There were some
      inconsistent between-year differences with higher ratings in 2012 for 3 outcomes
      and higher ratings in 2014 for 5 outcomes. However, for 25 questions relative to
      climate change, sea level rise, and the personal and ecological effects of sea
      level rise, self-evaluation of science knowledge, independent of years of
      education, was the factor that entered 23 of the models, accounting for the most
      variability in ratings. People who believed they had a "high knowledge" (#4) or
      "very high knowledge" (#5) of science rated all issues as more important than did
      those people who rated their own scientific knowledge as average or below
      average.

PMID- 29051799
TI  - Red cell genotyping precision medicine: a conference summary.
AB  - This review summarizes the salient points of the symposium 'Red Cell Genotyping
      2015: Precision Medicine' held on 10 September 2015 in the Masur Auditorium of
      the National Institutes of Health. The specific aims of this 6th annual symposium
      were to: (1) discuss how advances in molecular immunohematology are changing
      patient care; (2) exemplify patient care strategies by case reports (clinical
      vignettes); (3) review the basic molecular studies and their current implications
      in clinical practice; (4) identify red cell genotyping strategies to prevent
      alloimmunization; and (5) compare and contrast future options of red cell
      genotyping in precision transfusion medicine. This symposium summary captured the
      state of the art of red cell genotyping and its contribution to the practice of
      precision medicine.

PMID- 29051800
TI  - Current strategies for salvage treatment for relapsed classical Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is curable in 70-80% of patients with first-line therapy.
      However, relapses occur in a minority of patients with favorable early stage
      disease and are more frequent in patients with advanced HL. Salvage chemotherapy
      followed by high-dose chemotherapy and autologous stem cell transplant (ASCT) for
      patients with chemotherapy-sensitive disease is a standard treatment sequence for
      relapsed or refractory (rel/ref) HL. Patients who achieve complete response prior
      to ASCT have better survival outcomes. The choice of salvage chemotherapy therapy
      is becoming increasingly difficult in the era of novel agents, as there are no
      randomized studies to guide the choice of a second-line regimen. In this article,
      we will review current salvage therapy options, including combination
      chemotherapy and novel-agent-based salvage regimens for rel/ref HL.

PMID- 29051802
TI  - Radotinib and its clinical potential in chronic-phase chronic myeloid leukemia
      patients: an update.
AB  - Although imatinib has dramatically improved major outcomes in patients with
      chronic myeloid leukemia (CML), there are newer tyrosine kinase inhibitors (TKIs)
      approved worldwide for the treatment of resistant cases, and two second
      generation TKIs (dasatinib, nilotinib) are approved in some nations for treating
      patients in the upfront setting. Radotinib (IY5511HCL, Supect(r)) is a novel and
      selective second-generation BCR-ABL1 TKI, which is currently approved in Korea
      for the treatment of patients with CML both in the upfront and salvage settings.
      This review mainly focuses on the clinical potential of radotinib in patients
      with CML in chronic phase in terms of efficacy and safety.

PMID- 29051801
TI  - Current and emerging factor VIII replacement products for hemophilia A.
AB  - Hemophilia A is a congenital X-linked bleeding disorder caused by coagulation
      factor VIII (FVIII) deficiency. Routine infusion of factor replacement products
      is the current standard of care; however, the development of alloantibodies
      against FVIII remains a challenge. The treatment of hemophilia has undergone
      major advances over the past century to improve safety, effectiveness,
      manufacturing, and convenience of factor products. Major recent advances in the
      treatment of hemophilia A include the emergence of extended half-life products,
      factor VIII orthologs, and gene therapy products. Extended half-life products
      were designed to decrease the frequency of infusions, but only modest half-life
      extension is achieved. Factor VIII orthologs featuring lower cross-reactivity
      with anti-FVIII antibodies may be less susceptible to inactivation by inhibitors.
      Meanwhile, gene therapy may potentially provide a cure for hemophilia A, thus
      abrogating the need for protein-based factor replacement. This review aims to
      discuss current and emerging FVIII replacement products for hemophilia A.

PMID- 29051803
TI  - Midostaurin: a novel therapeutic agent for patients with FLT3-mutated acute
      myeloid leukemia and systemic mastocytosis.
AB  - The development of FLT3-targeted inhibitors represents an important paradigm
      shift in the management of patients with highly aggressive fms-like tyrosine
      kinase 3-mutated (FLT3-mut) acute myeloid leukemia (AML). Midostaurin is an
      orally administered type III tyrosine kinase inhibitor which in addition to FLT3
      inhibits c-kit, platelet-derived growth factor receptors, src, and vascular
      endothelial growth factor receptor. Midostaurin is the first FLT3 inhibitor that
      has been shown to significantly improve survival in younger patients with FLT3
      mut AML when given in combination with standard cytotoxic chemotherapy based on
      the recently completed RATIFY study. Its role for maintenance therapy after
      allogeneic transplantation and use in combination with hypomethylating agents for
      older patients with FLT3-mut has not yet been defined. Midostaurin also has
      recently been shown to have significant activity in systemic mastocytosis and
      related disorders due to its inhibitory effect on c-kit bearing a D816V mutation.
      Activation of downstream pathways in both of these myeloid malignancies likely
      plays an important role in the development of resistance, and strategies to
      inhibit these downstream targets may be synergistic. Incorporating patient
      factors and tumor characteristics, such as FLT3 mutant to wild-type allele ratios
      and resistance mutations, likely will be important in the optimization of
      midostaurin and other FLT3 inhibitors in the treatment of myeloid neoplasms.

PMID- 29051805
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/2040620717693972.].

PMID- 29051804
TI  - Review of recombinant anti-haemophilic porcine sequence factor VIII in adults
      with acquired haemophilia A.
AB  - Acquired haemophilia A (AHA) is a rare, serious bleeding disorder most often
      encountered in elderly patients. The mainstay of haemostatic management is with
      bypassing agents (BPAs) including recombinant activated factor VII (rFVIIa) and
      activated prothrombin complex concentrates (aPCCs). Their major limitation is
      incomplete efficacy, potential risk for thrombosis and the lack of routine
      laboratory assays for monitoring treatment response. Plasma-derived porcine FVIII
      (pd-pFVIII, Hyate C(r)), first used in the 1950s for the management of congenital
      haemophilia, has sufficient sequence homology to be haemostatic in humans, but
      the lack of complete homology facilitates efficacy even in the presence of human
      allo- and autoantibodies against human FVIII (hFVIII). In a small phase II/III
      study, recombinant porcine FVIII (rpFVIII, Obizur(r), OBI-1, susoctocog alfa) was
      shown to be safe and effective for the management of bleeding episodes in
      patients with AHA with anti-porcine FVIII (anti-pFVIII) antibody levels of 20
      BU/ml or less. Treatment outcome was judged on clinical response and FVIII levels
      after an initial fixed dose of 200 IU/kg. The rise in FVIII levels showed
      considerable inter-individual variability and was significantly influenced by the
      presence of anti-pFVIII antibodies. Based on the baseline levels of anti-pFVIII
      antibodies and response to treatment, three potential patient groups were
      identifiable. In the first group, the absence of cross-reacting antibodies was
      associated with supra-therapeutic FVIII levels, fewer infusions and lower rpFVIII
      utilization per treatment episode. The second group had patients with low levels
      of cross-reacting anti-pFVIII antibodies (0.8-5 BU/ml) with near-normal response
      to rpFVIII. The last group had higher titres of anti-pFVIII antibody (10-30
      BU/ml) associated with lower FVIII levels, more infusions and higher consumption
      of rpFVIII. We propose a new treatment algorithm for the haemostatic management
      of AHA that includes the potential first-line clinical use of rpFVIII that takes
      into account availability of anti-pFVIII antibody results, titre of anti-pFVIII
      antibodies and severity of bleeding episode.

PMID- 29051806
TI  - Synthetic lectin arrays for the detection and discrimination of cancer associated
      glycans and cell lines.
AB  - Aberrant glycosylation is a hallmark of various disease states, including cancer,
      and effective detection and discrimination between healthy and diseased cells is
      an important challenge for the diagnosis and treatment of many diseases. Here, we
      describe the use of boronic acid functionalized synthetic lectins (SLs) in an
      array format for the differentiation of structurally similar cancer associated
      glycans and cancer cell lines; discrimination is based on subtle variations in
      glycosylation patterns. We further demonstrate the utility of our SLs in
      recognizing glycoproteins with up to 50-fold selectivity, even in 95% human
      serum. Given their robust and selective nature, these SLs were able to
      effectively distinguish (a) five structurally similar glycans with 94% accuracy;
      (b) seven normal, cancerous and metastatic colon cancer cell lines, including
      three isogenic cell lines, with 92% accuracy; and (c) these same seven cell lines
      using a guided statistical analysis to improve our analysis to 97% accuracy. In
      total, these data suggest that an SL-based array will be useful for the diagnosis
      of cancer.

PMID- 29051807
TI  - Trelliswork and Craquelure.
AB  - Consider a mosaic image, the edges of the tesserae being unrelated to pictorial
      content. Depending upon grout color, the picture is seen as uninterrupted "behind
      bars" or divided into tiles by "cracks" as in an ancient oil painting. The
      phenomenology is explored.

PMID- 29051809
TI  - Impact of expansion and redifferentiation under hypothermia on chondrogenic
      capacity of cultured human septal chondrocytes.
AB  - A critical limitation in the cultivation of cartilage for tissue engineering is
      the dedifferentiation in chondrocytes, mainly during in vitro amplification.
      Despite many previous studies investigating the influence of various conditions,
      no data exist concerning the effects of hypothermia. Our aim has been to
      influence chondrocyte dedifferentiation in vitro by hypothermic conditions.
      Chondrocytes were isolated from cartilage biopsies and seeded in monolayer and in
      three-dimensional pellet-cultures. Each cell culture was either performed at 32.2
      degrees C or 37 degrees C during amplification. Additionally, the influence of
      the redifferentiation of chondrocytes in three-dimensional cell culture was
      examined at 32.2 degrees C and 37 degrees C after amplification at 32.2 degrees C
      or 37 degrees C. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium (MTS) assay was used to measure cell proliferation in
      monolayer, whereas the polymerase chain reaction and immunohistochemical and
      histological staining were used in three-dimensional pellet-cultures. Real-time
      polymerase chain reaction was employed to measure the relative expression of the
      target genes collagen II, collagen I, aggrecan and versican. Ratios were
      estimated between collagen II/collagen I and aggrecan/versican to evaluate
      differentiation. A higher value of these ratios indicated an advantageous status
      of differentiation. In monolayer, hypothermia at 32.2 degrees C slowed down the
      proliferation rate of chondrocytes significantly, being up to two times lower at
      32.2 degrees C compared with culture at 37 degrees C. Simultaneously, hypothermia
      in monolayer decelerated dedifferentiation. The ratio of aggrecan/versican was
      significantly higher at 32.2 degrees C compared with that at 37 degrees C. In
      three-dimensional pellet-culture, the chondrocytes redifferentiated at 32.2
      degrees C and at 37 degrees C, and this process is more distinct at 37 degrees C
      than at 32.2 degrees C. Similar results were obtained for the ratios of collagen
      II/collagen I and aggrecan/versican and were supported by immunochemical and
      histological staining. Thus, hypothermic conditions for chondrocytes are mainly
      advantageous in monolayer culture. In three-dimensional pellet-culture,
      redifferentiation predominates at 37 degrees C compared with at 32.2 degrees C.
      In particular, the results from the monolayer cultures show potential in the
      avoidance of dedifferentiation.

PMID- 29051808
TI  - Making microenvironments: A look into incorporating macromolecular crowding into
      in vitro experiments, to generate biomimetic microenvironments which are capable
      of directing cell function for tissue engineering applications.
AB  - Biomimetic microenvironments are key components to successful cell culture and
      tissue engineering in vitro. One of the most accurate biomimetic
      microenvironments is that made by the cells themselves. Cell-made
      microenvironments are most similar to the in vivo state as they are cell-specific
      and produced by the actual cells which reside in that specific microenvironment.
      However, cell-made microenvironments have been challenging to re-create in vitro
      due to the lack of extracellular matrix composition, volume and complexity which
      are required. By applying macromolecular crowding to current cell culture
      protocols, cell-made microenvironments, or cell-derived matrices, can be
      generated at significant rates in vitro. In this review, we will examine the
      causes and effects of macromolecular crowding and how it has been applied in
      several in vitro systems including tissue engineering.

PMID- 29051810
TI  - Controlled dexamethasone delivery via double-walled microspheres to enhance long
      term adipose tissue retention.
AB  - Current materials used for adipose tissue reconstruction have critical
      shortcomings such as suboptimal volume retention, donor-site morbidity, and poor
      biocompatibility. The aim of this study was to examine a controlled delivery
      system of dexamethasone to generate stable adipose tissue when mixed with
      disaggregated human fat in an athymic mouse model for 6 months. The hypothesis
      that the continued release of dexamethasone from polymeric microspheres would
      enhance both adipogenesis and angiogenesis more significantly when compared to
      the single-walled microsphere model, resulting in long-term adipose volume
      retention, was tested. Dexamethasone was encapsulated within single-walled
      poly(lactic-co-glycolic acid) microspheres (Dex SW MS) and compared to
      dexamethasone encapsulated in a poly(lactic-co-glycolic acid) core surrounded by
      a shell of poly-l-lactide. The double-walled polymer microsphere system in the
      second model was developed to create a more sustainable drug delivery process.
      Dexamethasone-loaded poly(lactic-co-glycolic acid) microspheres (Dex SW MS) and
      dexamethasone-loaded poly(lactic-co-glycolic acid)/poly-l-lactide double-walled
      microspheres (Dex DW MS) were prepared using single and double emulsion/solvent
      techniques. In vitro release kinetics were determined. Two doses of each type of
      microsphere were examined; 50 and 27 mg of Dex MS and Dex DW MS were mixed with
      0.3 mL of human lipoaspirate. Additionally, 50 mg of empty MS and lipoaspirate
      only controls were examined. Samples were analyzed grossly and histologically
      after 6 months in vivo. Mass and volume were measured; dexamethasone microsphere
      containing samples demonstrated greater adipose tissue retention compared to the
      control group. Histological analysis, including hematoxylin and eosin and CD31
      staining, indicated increased vascularization (p < 0.05) within the Dex MS
      containing samples. Controlled delivery of adipogenic factors, such as
      dexamethasone via polymer microspheres, significantly affects adipose tissue
      retention by maintaining healthy tissue formation and vascularization. Dex DW MS
      provide an improved model to former Dex SW MS, resulting in notably longer
      release time and, consequently, larger volumes of adipose retained in vivo. The
      use of microspheres, specifically double-walled, as vehicles for controlled drug
      delivery of adipogenic factors therefore present a clinically relevant model of
      adipose retention that has the potential to greatly improve soft tissue repair.

PMID- 29051811
TI  - Serum uric acid levels are associated with homeostasis model assessment in obese
      nondiabetic patients: HOMA and uric acid.
AB  - BACKGROUND: Hyperuricemia leads to insulin resistance, whereas insulin resistance
      decreases renal excretion of uric acid. The aim of this study was to evaluate
      whether there is a correlation between serum uric acid levels with homeostatic
      model assessment (HOMA) 1 in nondiabetic patients. METHODS: We evaluated 88
      nondiabetic patients, in whom uric acid levels were measured, in all of them HOMA
      of beta-cell function (HOMA 1B) and HOMA of insulin resistance (HOMA 1IR) scores
      were performed. Uric acid and the HOMA 1 values were correlated using the Pearson
      coefficient. RESULTS: We did not find any correlation between uric acid levels
      with both HOMA 1B (r = 0.102, p = 0.343), nor with HOMA 1IR (r = 0.158, p =
      0.117). When patients were analyzed by sex, we found a significant correlation
      with HOMA 1IR (0.278, p = 0.01), but not with HOMA 1B (0.138, p = 0.257) in
      women. We found a correlation with HOMA 1B in men (r = 0.37, p = 0.044), but not
      with HOMA 1IR: 0.203, p = 0.283. The analysis performed based on body mass index
      did not show correlation in the patients with normal weight, (HOMA 1B r = 0.08, p
      = 0.5, HOMA 1IR = 0.034, p = 0.793), nor in the patients who were overweight
      (HOMA 1B: r = 0.05, p = 0.76, HOMA 1IR r = 0.145, p = 0.43). However, a
      significant correlation between uricemia with both HOMA 1B (0.559, p < 0.001),
      and HOMA 1IR (0.326, p < 0.05), was observed in obese patients. CONCLUSION: Our
      results suggest that serum uric acid levels seem to be associated with insulin
      resistance in women, and in obese patients, but not in nonobese men. Uric acid
      also modifies beta-cell function in men and in obese patients.

PMID- 29051812
TI  - Patients' perceptions on the usability of the SurePalTM self-injection device for
      Omnitrope(r): a questionnaire-based observational study conducted in paediatric
      patients in France.
AB  - BACKGROUND: A questionnaire-based survey was conducted to evaluate attitudes
      towards a reusable self-injection system, SurePalTM, among paediatric patients
      with growth disturbances who were prescribed treatment with somatropin
      (Omnitrope(r)) as part of routine clinical practice. METHODS: This cross
      sectional survey was incorporated into the multinational, multi-centre,
      noninterventional PAtients TReated with Omnitrope(r) (PATRO) Children study.
      Questions were mainly focused on five areas: the attractiveness of SurePalTM;
      training received; use of the device; opinion of the low-drug wastage system;
      experience compared with previous devices used (among pretreated patients).
      RESULTS: Final results from participants in France are reported. Completed
      questionnaires were returned by 409 participants. Most patients (55%) were male
      and 89% were recombinant human growth hormone (rhGH)-treatment naive. Around 57%
      of children completed the questionnaire by themselves, while 43% had help from a
      family member/other person. The mean (standard deviation) age of all participants
      was 11.3 (3.6) years, and most patients were aged 10-12 years (n = 126) or 13-15
      years (n = 117). Overall, 86% of patients reported that preparing SurePalTM for
      injection was easy/very easy. Similarly, 83% reported that performing injections
      with SurePalTM was easy/very easy. The attractiveness of SurePalTM was rated as
      good/excellent by the majority (85%) of patients; this proportion was similarly
      high (> 80%) across all age groups. The dose-memory function was rated as
      helpful/very helpful by 54% of patients. Of the 174 patients who reported using
      the low drug-waste feature, 90% found it to be helpful/very helpful. Among the 24
      pretreated patients, 17 reported that SurePalTM was better/much better than their
      previous device. CONCLUSIONS: This questionnaire-based survey conducted in a
      large cohort of paediatric patients with growth disturbances from France confirms
      the ease of use of SurePalTM to support daily administration of Omnitrope(r)
      across all age groups. The demonstrated acceptability of the device may help to
      improve patient adherence to long-term daily treatment with rhGH.

PMID- 29051813
TI  - Differential impact of various reactive oxygen species (ROS) on HIF-1alpha/p53
      direct interaction in SK-N-MC neuroblastoma cells.
AB  - BACKGROUND: A vital property of eukaryotic cells physiology is their rather quick
      response to variation of oxygen tension, mainly by a transcription factor known
      as hypoxia-inducible factor-1 (HIF-1). Aside from its transcriptional regulation,
      other mechanisms, such as post translational modifications and protein-protein
      interactions, the interaction between HIF-1alpha and p53 has attracted more
      attention mainly due to simultaneous enhancement in the protein levels of these
      two anti- and pro-apoptotic vital transcriptional factors within the ROS-stressed
      cells. METHODS: In this study, we measured cell viability following exposure of
      the cells to H2O2, menadione and Cobalt Chloride by MTT, and ROS content was
      measured under the same condition. The immunoblotting technique has been used to
      establish the presence and amount of Caspase, HIF-1alpha and p53 proteins. Then,
      the effect of different ROS on interaction between HIF-1alpha and p53 proteins
      was examined by co-immunoprecipitation. RESULTS: The results showed that cells
      viability and intracellular ROS content were modulated in response to menadione,
      H2O2 and Cobalt Chloride. These agents had different influence on HIF-1alpha
      signaling pathways as well as its interactions with p53 protein. It appeared that
      direct communication between HIF-1alpha and p53 proteins by ROS stresses, under
      both normoxic and hypoxic conditions, was governed by HIF-1alpha at a certain
      induced level. CONCLUSIONS: Our data indicated that stabilization, a prerequisite
      for communication, of HIF-1alpha is dependent to the types of free radicals.

PMID- 29051814
TI  - Using 4+ to grade near-normal muscle strength does not improve agreement.
AB  - BACKGROUND: Manual assessment of muscle strength is often graded using the
      ordinal Medical Research Council (MRC) scale. The scale has a number of inherent
      weaknesses, including poorly defined limits between grades '4' and '5' and very
      large differences in the span of muscle strength encompassed by each of the six
      grades. It is not necessarily obvious how to convert a manual muscle test finding
      into an MRC grade. Several modifications which include intermediate grades have
      been suggested to improve the MRC scale and the current study examines whether
      agreement improves and variation in ratings decrease, with an intermediate grade
      between '4' and '5', in circumstances where such a grade would seem appropriate.
      The present study examined the hypothesis, that a modified MRC-scale which
      included the commonly used '4+' option, resulted in greater agreement between
      clinicians compared to the standard MRC-scale. METHOD: A questionnaire containing
      five simple clinical cases were distributed to a large convenience sample of
      chiropractors in Northern Europe, with instructions to grade the described muscle
      strength findings using the MRC scale. The scale was adapted (with/without an
      intermediate '4+' grade) depending on the preference of the individual
      respondent. The cases were designed in such a way as to suggest a muscle weakness
      in the grey area between '4' and '5', i.e. grade '4+' on the modified MRC scale.
      RESULTS: A total of 225 questionnaires were returned (7% response rate). The
      average percentage agreement (across cases) in the standard MRC group was 64%
      [range 51%: 73%] (grade '4' in all cases). In the modified MRC group, the
      corresponding findings was 48% [38%: 74%] (grade '4' or '4+' in all cases). The
      mean average deviation analogue in the standard MRC group was 0.34 (range 0.34:
      0.40), compared to 0.51 (range 0.39: 0.73) in the modified MRC group, indicating
      greater dispersion of scores in the modified MRC group. The Fleiss kappa was 0.02
      (p < 0.001) and 0.13 (p < 0.001), respectively. CONCLUSIONS: Contrary to the
      original hypothesis, introduction of a '4+' grade did not clearly improve
      agreement or variability of ratings, despite eliminating the physical muscle
      testing by providing written descriptions of test findings and specifically
      designing these to suggest a weakness of grade '4+'.

PMID- 29043063
TI  - A survey of working conditions within biomedical research in the United Kingdom.
AB  - Background: Many recent articles have presented a bleak view of career prospects
      in biomedical research in the US. Too many PhDs and postdocs are trained for too
      few research positions, creating a "holding-tank" of experienced senior postdocs
      who are unable to get a permanent position. Coupled with relatively low salaries
      and high levels of pressure to publish in top-tier academic journals, this has
      created a toxic environment that is perhaps responsible for a recently observed
      decline in biomedical postdocs in the US, the so-called "postdocalypse". Methods:
      In order to address the gulf of information relating to working habits and
      attitudes of UK-based biomedical researchers, a link to an online survey was
      included in an article published in the Guardian newspaper. Survey data were
      collected between 21 st March 2016 and 6 th November 2016 and analysed to examine
      discrete profiles for three major career stages: the PhD, the postdoc and the
      principal investigator. Results: Overall, the data presented here echo trends
      observed in the US: The 520 UK-based biomedical researchers responding to the
      survey reported feeling disillusioned with academic research, due to the low
      chance of getting a permanent position and the long hours required at the bench.
      Also like the US, large numbers of researchers at each distinct career stage are
      considering leaving biomedical research altogether. Conclusions: There are
      several systemic flaws in the academic scientific research machine - for example
      the continual overproduction of PhDs and the lack of stability in the early-mid
      stages of a research career - that are slowly being addressed in countries such
      as the US and Germany. These data suggest that similar flaws also exist in the
      UK, with a large proportion of respondents concerned about their future in
      research. To avoid lasting damage to the biomedical research agenda in the UK,
      addressing such concerns should be a major priority.

PMID- 29051816
TI  - Eptifibatide is associated with significant cost savings and similar clinical
      outcomes to abciximab when used during primary percutaneous coronary intervention
      for ST-elevation myocardial infarction: An observational cohort study of 3863
      patients.
AB  - INTRODUCTION: Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in
      patients with ST-segment elevation myocardial infarction treated with primary
      percutaneous coronary intervention. There are few studies directly comparing
      these agents. The aim of this study was to assess whether eptifibatide is a safe
      and cost-effective alternative to abciximab in the treatment of primary
      percutaneous coronary intervention for ST-segment elevation myocardial
      infarction. METHODS: This was an observational cohort study of 3863 patients who
      received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary
      intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa
      inhibitor were excluded. Time to first major adverse cardiac event defined as
      death, non-fatal myocardial infarction, stroke or target vessel
      revascularization, and total hospital costs were compared between the groups.
      RESULTS: In all, 1741 patients received abciximab with 2122 receiving
      eptifibatide. Patients who received eptifibatide had higher rates of previous
      MI/percutaneous coronary intervention and were more likely to undergo a procedure
      from the radial route. Unadjusted Kaplan-Meier analysis revealed no significant
      difference in the 1-year event rates between patients given eptifibatide versus
      abciximab (p = 0.201). Age-adjusted Cox analysis demonstrated no difference in 1
      year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95%
      confidence interval: 0.73-1.39), which persisted after multivariate adjustment
      (hazard ratio: 0.92; 95% confidence interval: 0.79-1.56) including the
      incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval:
      0.71-1.44). Eptifbatide was associated with significant cost savings being 87%
      cheaper overall compared to abciximab (on average L650 cheaper per patient and
      saving approximately L950,000). CONCLUSION: This observational data suggest that
      eptifibatide is associated with similar outcomes and significant cost savings
      compared to abciximab when used in patients with ST-segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention.

PMID- 29051817
TI  - Myocardial remodelling and recovery in dilated cardiomyopathy.
AB  - Myocardial reverse remodeling has been reported to occur in 25-70% of patients
      with dilated cardiomyopathy. It is not yet fully understood whether remodeling
      represents disease remission or cure and which hearts retain this capacity to
      recover. In this review article we discuss the capacity for recovery in DCM, the
      prognostic implications of this recovery and potential clinical and imaging
      predictors for myocardial remodeling.

PMID- 29051818
TI  - Successful discontinuation of immunoglobulin G replacement at age 10 in a patient
      with immunoglobulin G2 deficiency.
AB  - CONTEXT: Immunoglobulin G2 deficiency that persists beyond the age of 6 years is
      likely to be permanent. CASE REPORT: We report on a young Japanese female,
      diagnosed as having immunoglobulin G2 deficiency and low anti-pneumococcal
      immunoglobulin G2 antibody levels when 3 years old, with a subsequent medical
      history of frequent respiratory infections and asthma. Monthly intravenous
      immunoglobulin replacement therapy was started at 4 years of age. After 8 years
      of age, an anti-pneumococcal immunoglobulin G2 trough level could be maintained
      with administration intervals longer than 6 weeks, and after 9 years and 10
      months of age, therapy was discontinued. The frequency of hospital admissions was
      reduced by the introduction of the replacement therapy (from 8.4 times/year
      before the introduction to 1.1 times/year during the therapy). The patient was
      also able to discontinue daily medications for asthma, and serum immunoglobulin
      G2 was maintained at a normal level even after the cessation of replacement
      therapy. CONCLUSION: Termination of immunoglobulin replacement therapy in a
      patient with a symptomatic immunoglobulin G2 deficiency is possible, even for a
      child older than 6 years.

PMID- 29051819
TI  - Estimating national dioxins and furans emissions, major sources, intake doses,
      and temporal trends in Iran from 1990-2010.
AB  - BACKGROUND: Polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDFs)
      are highly toxic persistent organic pollutants (POPs), which can cause various
      health outcomes, such as cancer. As a part of the National and Sub-national
      Burden of Disease Study (NASBOD), we aimed to estimate dioxins and furans
      national emissions, identify their main sources, estimate daily intake doses, and
      assess their trend from 1990-2010 in Iran. METHODS: The Toolkit for
      Identification and Quantification of Releases of Dioxins, Furans and Other
      Unintentional POPs, which is developed by the United Nations Environment
      Programme (UNEP 2013), was used to estimate the emissions of PCDD/PCDFs from
      several sources into the air, water, land, residue, and other products. The daily
      intake doses were estimated using a linear regression of estimated emissions by
      UNEP Toolkit and average intake doses in other countries. Finally, the trend of
      PCDD/PCDFs emissions and daily intake doses were explored from 1990-2010.
      RESULTS: The total emissions were estimated as 960 g Toxic Equivalents (g TEQ)
      for 1990 and 1957 g TEQ for 2010 (18.2 and 26.8 g TEQ per million capita,
      respectively). The estimations suggest that albeit contribution of open burning
      to PCDD/PCDFs emissions has been declining from 1990 to 2010, it remained the
      major source of emissions in Iran contributing to about 45.8% out of total
      emissions in 1990 to 35.7% in 2010. We further found that PCDD/PCDFs are mostly
      emitted into the ambient air, followed by residue, land, products, and water. The
      daily intake doses were estimated to be 3.1 and 5.4 pg TEQ/kg bw/day for 1990 and
      2010, respectively. We estimated an increasing trend for PCDD/PCDFs emissions and
      intake doses in Iran from 1990-2010. CONCLUSIONS: The high levels of emissions,
      intake doses, and their increasing trend in Iran may pose a substantial health
      risk to the Iranian population. Further studies with more rigorous methods are
      recommended but this should not circumvent taking appropriate policy actions
      against these pollutants. Currently, Iran has no standard for dioxins and furans.
      Adaptation of the World Health Organization recommended guidelines might be an
      appropriate starting point to control dioxins and furans emissions.

PMID- 29051821
TI  - Mindfulness-Based Childbirth and Parenting (MBCP): Innovation in Birth
      Preparation to Support Healthy, Happy Families.

PMID- 29051820
TI  - VqMAPKKK38 is essential for stilbene accumulation in grapevine.
AB  - Vitis species, including grapevine, produce a class of secondary metabolites
      called stilbenes that are important for plant disease resistance and can have
      positive effects on human health. Mitogen-activated protein kinase (MAPK)
      signaling cascades not only play key roles in plant defense responses but also
      contribute to stilbene biosynthesis in grapevine. MAPKKKs function at the upper
      level of the MAPK network and initiate signaling through this pathway. In this
      study, a Raf-like MAPKKK gene, VqMAPKKK38, was identified and functionally
      characterized from the Chinese wild grapevine V. quinquangularis accession
      'Danfeng-2'. We observed that VqMAPKKK38 transcript levels were elevated by
      powdery mildew infection, high salinity conditions and chilling stresses, as well
      as in response to treatments by the hormones salicylic acid (SA), methyl
      jasmonate (MeJA), ethylene (Eth) and abscisic acid (ABA). In addition, based on
      both transient overexpression and gene suppression of VqMAPKKK38 in grapevine
      leaves, we found that VqMAPKKK38 positively regulates stilbene synthase
      transcription and stilbene accumulation probably by mediating the activation of
      the transcription factor MYB14. In addition, both hydrogen peroxide (H2O2) and
      calcium influx activated VqMAPKKK38 expression and stilbene biosynthesis, which
      suggests that VqMAPKKK38 may be involved in the calcium signaling and ROS
      signaling pathways.

PMID- 29051822
TI  - Food for Life: evaluation of the impact of the Hospital Food Programme in England
      using a case study approach.
AB  - OBJECTIVES: To evaluate the impact and challenges of implementing a Food for Life
      approach within three pilot NHS sites in 2014/2015 in England. Food for Life is
      an initiative led by the Soil Association, a non-governmental organisation in the
      UK that aims to encourage a healthy, sustainable food culture across communities.
      DESIGN: A case-study approach was undertaken using semi-structured interviews
      with staff and key stakeholders together with analysis of relevant documents such
      as meeting minutes, strategic plans and reports. SETTING: Three NHS Trusts in
      England. PARTICIPANTS: Staff and key stakeholders. MAIN OUTCOME MEASURES:
      Synthesis of key findings from semi-structured interviews and analysis of
      relevant documents. RESULTS: Key themes included the potential to influence
      contracting processes; measuring quality; food for staff and visitors; the role
      of food in hospitals, and longer term sustainability and impact. Participants
      reported that adopting the Food for Life approach had provided enormous scope to
      improve the quality of food in hospital settings and had provided levers and
      external benchmarks for use in contracting to help drive up standards of the food
      provided by external contractors for patients and staff. This was demonstrated by
      the achievement of an FFLCM for staff and visitor catering in all three
      organisations. CONCLUSIONS: Participants all felt that the importance of food in
      hospitals is not always recognised. Engagement with Food for Life can produce a
      significant change in the focus on food within hospitals, and help to improve the
      quality of food and mealtime experience for staff, visitors and patients.

PMID- 29051823
TI  - Giant cell aortitis leading to Stanford type B and type A aortic dissection.
AB  - This report provides a rare histological example and the appropriate management
      of spontaneous aortic dissection secondary to giant cell arteritis.

PMID- 29051824
TI  - Pure akinesia with gait freezing: a clinicopathologic study.
AB  - BACKGROUND: Pure akinesia with gait freezing is a rare syndrome with few
      autopsied cases. Severe freezing of gait occurs in the absence of bradykinesia
      and rigidity. Most autopsies have revealed progressive supranuclear palsy. We
      report the clinical and postmortem findings of two patients with pure akinesia
      with gait freezing, provide video recordings of these patients, and review the
      literature describing similar cases. We also discuss bradykinesia, hypokinesia
      and akinesia in the context of this clinical syndrome. CASE PRESENTATION: Two
      patients with the syndrome of pure akinesia with gait freezing were examined by
      the same movement disorder specialist at least annually for 9 and 18 years. Both
      patients initially exhibited freezing, tachyphemia, micrographia and festination
      without bradykinesia and rigidity. Both autopsies revealed characteristic tau
      pathology of progressive supranuclear palsy, with nearly total neuronal loss and
      gliosis in the subthalamus and severe neuronal loss and gliosis in the globus
      pallidus and substantia nigra. Previously published postmortem studies revealed
      that most patients with this syndrome had progressive supranuclear palsy or
      pallidonigroluysian atrophy. CONCLUSIONS: Pallidonigroluysian degeneration
      produces freezing and festination in the absence of generalized slowing
      (bradykinesia). Freezing and festination are commonly regarded as features of
      akinesia. Akinesia literally means absence of movement, and akinesia is commonly
      viewed as an extreme of bradykinesia. The pure akinesia with gait freezing
      phenotype illustrates that bradykinesia and akinesia should be viewed as separate
      phenomena.

PMID- 29051825
TI  - Continuous glucose monitoring in neonates: a review.
AB  - Continuous glucose monitoring (CGM) is well established in the management of
      diabetes mellitus, but its role in neonatal glycaemic control is less clear. CGM
      has provided important insights about neonatal glucose metabolism, and there is
      increasing interest in its clinical use, particularly in preterm neonates and in
      those in whom glucose control is difficult. Neonatal glucose instability,
      including hypoglycaemia and hyperglycaemia, has been associated with poorer
      neurodevelopment, and CGM offers the possibility of adjusting treatment in real
      time to account for individual metabolic requirements while reducing the number
      of blood tests required, potentially improving long-term outcomes. However,
      current devices are optimised for use at relatively high glucose concentrations,
      and several technical issues need to be resolved before real-time CGM can be
      recommended for routine neonatal care. These include: 1) limited point accuracy,
      especially at low or rapidly changing glucose concentrations; 2) calibration
      methods that are designed for higher glucose concentrations of children and
      adults, and not for neonates; 3) sensor drift, which is under-recognised; and 4)
      the need for dynamic and integrated metrics that can be related to long-term
      neurodevelopmental outcomes. CGM remains an important tool for retrospective
      investigation of neonatal glycaemia and the effect of different treatments on
      glucose metabolism. However, at present CGM should be limited to research
      studies, and should only be introduced into routine clinical care once benefit is
      demonstrated in randomised trials.

PMID- 29051827
TI  - Membrane-like structure in the urinary bladder neck of a young cat: diagnosis and
      treatment using balloon dilatation and a balloon-expandable metallic stent.
AB  - CASE SUMMARY: A 33-month-old, spayed female domestic shorthair cat was referred
      to the Animal Health Trust for the investigation of urinary incontinence and
      straining to urinate. A membrane-like structure was detected in the bladder neck,
      which caused partial obstruction of the urinary bladder. A combination of
      different imaging techniques, including ultrasonography, radiography, CT and
      fluoroscopy, was essential in the diagnosis, surgical planning and treatment of
      this intravesicular stricture. During retrograde vaginourethrocystogram,
      unexpected subcapsular accumulation of contrast medium was seen around both
      kidneys on radiographs and confirmed with CT. Three different treatments were
      performed, including surgical debridement, balloon dilatation and placement of a
      self-expanding metallic stent across the stricture. Histopathology of the
      membrane was unable to differentiate whether the lesion was congenital or
      acquired. No urinary incontinence was observed 5 months after placement of the
      metallic stent. RELEVANCE AND NOVEL INFORMATION: This is the first reported case
      using fluoroscopic-guided balloon dilatation of the bladder neck for the
      treatment of a bladder neck stricture. Presence of renal subcapsular contrast
      medium secondary to a retrograde vaginourethrocystogram due to partial
      obstruction at the bladder neck in a cat has not been previously described.

PMID- 29051826
TI  - Apparent and standardized ileal nutrient digestibility of broiler diets
      containing varying levels of raw full-fat soybean and microbial protease.
AB  - BACKGROUND: Although soybean meal (SBM) is excellent source of protein in diets
      for poultry, it is sometimes inaccessible, costly and fluctuates in supply. The
      SBM can partially be replaced by full-fat SBM, but the meals prepared from raw
      full-fat soybean contain antinutritional factors. To avoid the risk of
      antinutritional factors, heat treatment is always advisable, but either excessive
      or under heating the soybean could negatively affect the quality. However, the
      potential for further improvement of SBM by supplementing with microbial enzymes
      has been suggested by many researchers. The objective of this study was to
      evaluate the performance and ileal nutrient digestibility of birds fed on diets
      containing raw soybeans and supplemented with microbial protease. METHODS: A 3 *
      2 factorial, involving 3 levels of raw full-fat soybean (RFFS; 0, 45 or 75 g/kg
      of diet) and 2 levels of protease (0 or 15,000 PROT/kg) was used. The birds were
      raised in a climate-controlled room. A nitrogen-free diet was also offered to a
      reference group from day 19 to 24 to determine protein and amino acid flow at the
      terminal ileum and calculate the standardized ileal digestibility of nutrients.
      On days 10, 24 and 35, body weight and feed leftover were recorded to calculate
      the body weight gain (BWG), feed intake (FI) and feed conversion ratio (FCR). On
      day 24, samples of ileal digesta were collected at least from two birds per
      replicate. RESULTS: When RFFS was increased from 0 to 75 g/kg of diet, the
      content of trypsin inhibitors was increased from 1747 to 10,193 trypsin
      inhibitors unit (TIU)/g of diets, and feed consumption of birds was also reduced
      (P < 0.05). Increasing RFFS level reduced the BWG from hatch 0 to 10 d (P < 0.01)
      and hatch to 24 d (P < 0.05). The BWG of birds from hatch to 35 was not
      significantly (P = 0.07) affected. Feed intake was also reduced (P < 0.05) during
      0 to 35 d. However, protease supplementation improved (P < 0.05) the BWG and FCR
      during 0 to 24 d. Rising levels of RFFS increased the weight of pancreas (P <
      0.001) and small intestine (P < 0.001) at day 24. Except for methionine, apparent
      and the corresponding standardized ileal digestibility of CP and AA were reduced
      (P < 0.01) by increasing levels of RFFS in diets. CONCLUSION: This study showed
      that some commercial SBM could be replaced by RFFS in broiler diets, without
      markedly compromising productivity. The AID and SID of CP and lysine were
      slightly improved by dietary supplementation of microbial protease.

PMID- 29051828
TI  - Intubation following high-dose rocuronium in a cat with protracted laryngospasm.
AB  - CASE SUMMARY: An 11-year-old spayed female domestic shorthair cat with a history
      of laryngospasm at induction of general anesthesia presented for dental
      evaluation and treatment. The cat was premedicated with hydromorphone (0.05
      mg/kg) and alfaxalone (0.5 mg/kg) intravenously, pre-oxygenated for 5 mins (3
      l/min, face mask) and anesthesia was induced with alfaxalone (to effect)
      intravenously. Lidocaine (0.1 ml, 2%) was applied topically to the arytenoid
      cartilages following loss of jaw tone. Laryngospasm was not noted during or
      immediately following lidocaine application. However, after waiting 60 s for the
      onset of effect of the topical lidocaine, laryngospasm was apparent. Orotracheal
      intubation by direct visualization was unsuccessful after four attempts by three
      anesthetists (with increasing levels of experience). At this point, a failed
      intubation was declared and the non-depolarising neuromuscular blocking agent
      rocuronium (1 mg/kg IV) given, resulting in arytenoid abduction and appropriate
      conditions for intubation. Successful intubation occurred 9 mins after induction
      of anesthesia. Oxygen was continuously supplemented throughout and arterial
      hemoglobin saturation with oxygen was never <94%. RELEVANCE AND NOVEL
      INFORMATION: To the authors' knowledge, this is the first report of the use of
      high-dose rocuronium to successfully resolve prolonged laryngospasm at induction
      of general anesthesia in a cat. Despite laryngospasm and a delay in achieving
      orotracheal intubation, low values for arterial hemoglobin saturation with oxygen
      (indicative of hypoxemia) were not observed, highlighting the benefits of pre
      oxygenation and apneic oxygenation. The principles of the Difficult Airway
      Society 2015 guidelines were followed in managing this difficult intubation.

PMID- 29051829
TI  - The efficacy of cladribine tablets in CIS patients retrospectively assigned the
      diagnosis of MS using modern criteria: Results from the ORACLE-MS study.
AB  - BACKGROUND: Multiple sclerosis (MS) diagnostic criteria have changed since the
      ORACLE-MS study was conducted; 223 of 616 patients (36.2%) would have met the
      diagnosis of MS vs clinically isolated syndrome (CIS) using the newer criteria.
      OBJECTIVE: The objective of this paper is to assess the effect of cladribine
      tablets in patients with a first clinical demyelinating attack fulfilling newer
      criteria (McDonald 2010) for MS vs CIS. METHODS: A post hoc analysis for
      subgroups of patients retrospectively classified as fulfilling or not fulfilling
      newer criteria at the first clinical demyelinating attack was conducted. RESULTS:
      Cladribine tablets 3.5 mg/kg (n = 68) reduced the risk of next attack or three
      month confirmed Expanded Disability Status Scale (EDSS) worsening by 74% vs
      placebo (n = 72); p = 0.0009 in patients meeting newer criteria for MS at
      baseline. Cladribine tablets 5.25 mg/kg (n = 83) reduced the risk of next attack
      or three-month confirmed EDSS worsening by 37%, but nominal significance was not
      reached (p = 0.14). In patients who were still CIS after applying newer criteria,
      cladribine tablets 3.5 mg/kg (n = 138) reduced the risk of conversion to
      clinically definite multiple sclerosis (CDMS) by 63% vs placebo (n = 134); p =
      0.0003. Cladribine tablets 5.25 mg/kg (n = 121) reduced the risk of conversion by
      75% vs placebo (n = 134); p < 0.0001. CONCLUSIONS: Regardless of the criteria
      used to define CIS or MS, 3.5 mg/kg cladribine tablets are effective in patients
      with a first clinical demyelinating attack. ClinicalTrials.gov registration: The
      ORACLE-MS study (NCT00725985).

PMID- 29051830
TI  - Prevalence of neutralising antibodies to interferon-beta and clinical response in
      Chinese patients with relapsing multiple sclerosis.
AB  - BACKGROUND: There are no data on neutralising antibodies to interferon-beta and
      its clinical implications in Chinese patients with multiple sclerosis (MS).
      OBJECTIVES: The objectives of this study were to investigate the prevalence of
      neutralising antibodies among Chinese patients with relapsing MS receiving
      interferon-beta (1a or 1b) and to study the association between neutralising
      antibodies and the clinical-radiological response. METHODS: We performed a cross
      sectional study on MS patients who received interferon-beta for 9 months or more,
      and evaluated the clinical response by relapses and magnetic resonance imaging
      lesions. Blood samples were evaluated for myxovirus resistance protein A (MxA)
      gene expression by polymerase chain reaction, anti-interferon-beta binding
      antibodies by enzyme-linked immunosorbent assay, and neutralising antibodies by
      cell-based MxA protein induction and luciferase reporter gene assays. Assay
      performances were evaluated by receiver operating characteristic analysis.
      RESULTS: Among 78 subjects recruited, 61/77 (79%) had anti-interferon-beta
      binding antibodies, and 22/78 (28%) had neutralising antibodies by MxA protein
      induction assay. The presence of high-titre neutralising antibodies was
      associated with poor clinical outcome (odds ratio 6.1, 95% confidence interval
      1.5-25.6, P = 0.013). The sensitivity and specificity for neutralising antibodies
      using MxA gene expression assay (cut-off 0.20) was 80% and 68%, respectively
      (area under the curve 0.71). CONCLUSIONS: Neutralising antibodies are associated
      with poor clinical outcome in Chinese patients with relapsing MS. MxA gene
      expression and protein induction assays are complimentary assays for neutralising
      antibody detection.

PMID- 29051831
TI  - Randomized controlled trial of an e-learning designed behavioral intervention for
      increasing physical activity behavior in multiple sclerosis.
AB  - BACKGROUND: Internet-delivered, behavioral interventions represent a cost
      effective, broadly disseminable approach for teaching persons with multiple
      sclerosis (MS) the theory-based skills, techniques, and strategies for changing
      physical activity. OBJECTIVES: This pilot, randomized controlled trial examined
      the efficacy of a newly developed Internet website based on e-learning approaches
      that delivered a theory-based behavior intervention for increasing physical
      activity and improving symptoms, walking impairment, and neurological disability.
      METHODS: Participants with MS (N = 47) were randomly assigned into behavioral
      intervention (n = 23) or waitlist control (n = 24) conditions delivered over a
      six-month period. Outcomes were administered before and after the six-month
      period using blinded assessors, and data were analyzed using analysis of
      covariance in SPSS. RESULTS: There was a significant, positive intervention
      effect on self-reported physical activity (P = 0.05, [Formula: see text] = 0.10),
      and non-significant improvement in objectively measured physical activity (P =
      0.24, [Formula: see text] = 0.04). There were significant, positive effects of
      the intervention on overall (P = 0.018, [Formula: see text] = 0.13) and physical
      impact of fatigue (P = 0.003, [Formula: see text] = 0.20), self-reported walking
      impairment (P = 0.047, [Formula: see text] = 0.10), and disability status (P =
      0.033, [Formula: see text] = 0.11). There were non-significant improvements in
      fatigue severity (P = 0.10, [Formula: see text] = 0.06), depression (P = 0.10,
      [Formula: see text] = 0.07) and anxiety (P = 0.06, [Formula: see text] = 0.09)
      symptoms, and self-reported disability (P = 0.10, [Formula: see text] = 0.07).
      CONCLUSIONS: We provide evidence for the efficacy of an Internet-based behavioral
      intervention with content delivered through interactive video courses grounded in
      e-learning principles for increasing physical activity and possibly improving
      secondary outcomes of fatigue, depression, anxiety, and walking
      impairment/disability in persons with MS.

PMID- 29051832
TI  - Mirror-image polymerase chain reaction.
AB  - The construction of mirror-image biological systems may open the next frontier
      for biomedical technology development and discovery. Here we have designed and
      chemically synthesized a mutant version of the thermostable Sulfolobus
      solfataricus P2 DNA polymerase IV (Dpo4) consisting of d-amino acids. With a
      total peptide length of 358 amino acid residues, it is the largest chemically
      synthesized d-amino acid protein reported to date. We show that the d-polymerase
      is able to amplify a 120-bp l-DNA sequence coding for the Escherichia coli 5S
      ribosomal RNA gene rrfB by mirror-image polymerase chain reaction, and that both
      the natural and mirror-image systems operate with strict chiral specificity. The
      development of efficient miPCR systems may lead to many practical applications,
      such as mirror-image systematic evolution of ligands by exponential enrichment
      for the selection of therapeutically promising nuclease-resistant l-nucleic acid
      aptamers.

PMID- 29051833
TI  - Anatomical and functional correlation in Susac syndrome: multimodal imaging
      assessment.
AB  - BACKGROUND: Susac's syndrome (SuS) is an uncommon disease characterized by
      retinal microangiopathy that may be assessed more accurately with optical
      coherence tomography angiography (OCTA), a new imaging technique which provides a
      retinal microvasculature map. The purpose of this case report is to describe the
      multimodal imaging findings of SuS correlating OCTA with functional tests. CASE
      PRESENTATION: Retrospective review of one case with clinical and imaging evidence
      of SuS. Color fundus photograph, fluorescein angiography (FA), OCTA,
      microperimetry (MP) and visual field (VF) tests were analyzed at the time of
      presentation and at 1- and 6-month visit following initiation of treatment. The
      study patient underwent standard treatment for SuS. The patient age was 31 year
      old and the baseline visual acuity was 20/60 and 20/20 in the right and left
      eyes, respectively. At presentation, FA showed branch retinal arterial occlusion
      within the macular area of the right eye and vascular leakage in the periphery of
      the left eye. OCTA demonstrated areas of superficial and deep retinal vascular
      plexuses hypoperfusion in both eyes. The OCTA segmentations in the outer retina
      and choriocapillaris were normal. The low VF and MP sensitivity signals precisely
      corresponded to the topography of decreased vascular perfusion seen on the OCTA
      density map in both eyes. Six months after specific SuS therapy, retinal vascular
      perfusion showed partial improvement in both eyes. CONCLUSION: OCTA may
      demonstrate superficial and deep retinal vascular non-perfusion without
      choriocapillary vasculature changes in SuS. This anatomical information given by
      OCTA corresponded to points of low sensitivity on functional tests represented by
      VF and MP.

PMID- 29051834
TI  - FDG avid breast cancer bone metastases silent on CT and scintigraphy: a case
      report with radiologic-pathologic correlation.
AB  - Bone is the one of the most common distant metastatic sites in breast cancer.
      Routine initial breast cancer staging evaluation typically includes computed
      tomography (CT) and skeletal scintigraphy while 18F fluorodeoxyglucose (FDG)
      positron emission tomography-computed tomography (PET-CT) is reserved for
      clinically high-risk cases. Since FDG PET-CT is not routinely performed during
      staging or surveillance evaluations, it is important for radiologists and
      clinicians to appreciate the limitations of bone metastasis detection on CT and
      scintigraphy. We present a case of bony metastases of invasive ductal carcinoma
      of the breast which were not detected on diagnostic CT or skeletal scintigraphy
      but were metabolically active on FDG PET-CT and evident on magnetic resonance. We
      provide a review of the literature and radiologic-pathologic correlation to
      explain the discordant imaging findings.

PMID- 29051835
TI  - Digital dashboards as tools for regional influenza monitoring.

PMID- 29051836
TI  - High agreement between the new Mongolian electronic immunization register and
      written immunization records: a health centre based audit.
AB  - INTRODUCTION: Monitoring of vaccination coverage is vital for the prevention and
      control of vaccine-preventable diseases. Electronic immunization registers have
      been increasingly adopted to assist with the monitoring of vaccine coverage;
      however, there is limited literature about the use of electronic registers in low
      and middle-income countries such as Mongolia. We aimed to determine the accuracy
      and completeness of the newly introduced electronic immunization register for
      calculating vaccination coverage and determining vaccine effectiveness within two
      districts in Mongolia in comparison to written health provider records. METHODS:
      We conducted a cross-sectional record review among children 2-23 months of age
      vaccinated at immunization clinics within the two districts. We linked data from
      written records with the electronic immunization register using the national
      identification number to determine the completeness and accuracy of the
      electronic register. RESULTS: Both completeness (90.9%; 95% CI: 88.4-93.4) and
      accuracy (93.3%; 95% CI: 84.1-97.4) of the electronic immunization register were
      high when compared to written records. The increase in completeness over time
      indicated a delay in data entry. CONCLUSION: Through this audit, we have
      demonstrated concordance between a newly introduced electronic register and
      health provider records in a middle-income country setting. Based on this
      experience, we recommend that electronic registers be accompanied by routine
      quality assurance procedures for the monitoring of vaccination programmes in such
      settings.

PMID- 29051837
TI  - Emergency Department demand associated with seasonal influenza, 2010 through
      2014, New South Wales, Australia.
AB  - INTRODUCTION: Influenza's impact on health and health care is underestimated by
      influenza diagnoses recorded in health-care databases. We aimed to estimate total
      and non-admitted influenza-attributable hospital Emergency Department (ED) demand
      in New South Wales (NSW), Australia. METHODS: We used generalized additive time
      series models to estimate the association between weekly counts of laboratory
      confirmed influenza infections and weekly rates of total and non-admitted
      respiratory, infection, cardiovascular and all-cause ED visits in NSW, Australia
      for the period 2010 through 2014. Visit categories were based on the coded ED
      diagnosis or the free-text presenting problem if no diagnosis was recorded.
      RESULTS: The estimated all-age, annual influenza-attributable respiratory,
      infection, cardiovascular and all-cause visit rates/100 000 population/year were,
      respectively, 120.6 (99.9% confidence interval [CI] 102.3 to 138.8), 79.7 (99.9%
      CI: 70.6 to 88.9), 14.0 (99.9% CI: 6.8 to 21.3) and 309.0 (99.9% CI: 208.0 to
      410.1). Among respiratory visits, influenza-attributable rates were highest among
      < 5-year-olds and >= 85-year-olds. For infection and all-cause visits, rates were
      highest among children; cardiovascular rates did not vary significantly by age.
      Annual rates varied substantially by year and age group, and statistically
      significant associations were absent in several years or age groups. Of the
      respiratory visits, 73.4% did not require admission. The non-admitted proportion
      was higher for the other clinical categories. Around 1 in 100 total visits and
      more than 1 in 10 respiratory or infection visits were associated with influenza.
      DISCUSSION: Influenza is associated with a substantial and annually varying
      burden of hospital-attended illness in NSW.

PMID- 29051838
TI  - Lessons learnt from a three-year pilot field epidemiology training programme.
AB  - PROBLEM: The Pacific region has widely dispersed populations, limited financial
      and human resources and a high burden of disease. There is an urgent need to
      improve the availability, reliability and timeliness of useable health data.
      CONTEXT: The purpose of this paper is to share lessons learnt from a three-year
      pilot field epidemiology training programme that was designed to respond to these
      Pacific health challenges. The pilot programme built on and further developed an
      existing field epidemiology training programme for Pacific health staff. ACTION:
      The programme was delivered in country by epidemiologists working for Pacific
      Public Health Surveillance Network partners. The programme consisted of five
      courses: four one-week classroom-based courses and one field epidemiology
      project. Sessions were structured so that theoretical understanding was achieved
      through interaction and reinforced through practical hands-on group activities,
      case studies and other interactive practical learning methods. OUTCOME: As of
      September 2016, 258 students had commenced the programme. Twenty-six course
      workshops were delivered and one cohort of students had completed the full five
      course programme. The programme proved popular and gained a high level of student
      engagement. DISCUSSION: Face-to-face delivery, a low student-to-facilitator
      ratio, substantial group work and practical exercises were identified as key
      factors that contributed to the students developing skills and confidence. Close
      engagement of leaders and the need to quickly evaluate and adapt the curriculum
      were important lessons, and the collaboration between external partners was
      considered important for promoting a harmonized approach to health needs in the
      Pacific.

PMID- 29051839
TI  - External quality assessment for arbovirus diagnostics in the World Health
      Organization Western Pacific Region, 2013-2016: improving laboratory quality over
      the years.
AB  - Arboviruses continue to pose serious public health threats in the World Health
      Organization (WHO) Western Pacific Region. As such, laboratories need to be
      equipped for their accurate detection. In 2011, to ensure test proficiency, the
      WHO Regional Office for the Western Pacific piloted an external quality
      assessment (EQA) programme for arbovirus diagnostics. By 2016, it had grown into
      a global programme with participation of 96 laboratories worldwide, including 25
      laboratories from 19 countries, territories and areas in the Region. The test
      performance of the 25 laboratories in the Region in 2016 was high with 23 (92%)
      reporting correct results in all specimens for dengue and chikungunya viruses.
      For Zika virus, 18 (72%) of the 25 laboratories reported correct results in all
      specimens, while seven (28%) demonstrated at least one error. When comparing
      iterations of this EQA programme in the Region between 2013 and 2016, the number
      of participating laboratories increased from 18 to 25. The first round only
      included dengue virus, while the latest round additionally included chikungunya,
      Zika and yellow fever viruses. Proficiency for molecular detection of dengue
      virus remained high (83-94%) over the four-year period. The observed proficiency
      for arbovirus diagnostics between 2013 and 2016 is an indicator of laboratory
      quality improvement in the Region.

PMID- 29051840
TI  - Syrian Refugee Women's Health in Lebanon, Turkey, and Jordan and Recommendations
      for Improved Practice.
AB  - Since 2011, an estimated nine million Syrian refugees have fled to neighboring
      countries, and over four million have fled to neighboring countries of Lebanon,
      Turkey, and Jordan. Seventy five percent of Syrian refugees are women and
      children. In times of conflict, women's health disproportionately suffers. Based
      on an assessment of academic literature and international policy and development
      reports, this study explores the vulnerabilities of Syrian women and girls in
      Lebanon, Turkey, and Jordan, and how these countries approach Syrian refugee
      women's health care. In all settings, sexual and gender-based violence, reduced
      use of modern contraceptives, menstrual irregularity, unplanned pregnancies,
      preterm birth, and infant morbidity are ongoing issues. Recommendations for
      improved practice include taking a multilevel approach to eliminate social and
      service delivery barriers that prevent access to care, conducting thorough needs
      assessments, and creating policy and programmatic solutions that establish long
      term care for Syrian refugee women.

PMID- 29051841
TI  - Perceived Cost Advantages and Disadvantages of Purchasing HIV Self-Testing Kits
      among Urban Tanzanian Men: An Inductive Content Analysis.
AB  - Impoverished men have lower rates of facility-based HIV counseling and testing
      and higher unknown HIV-positive status than women. Economic theory suggests that
      individuals will obtain an HIV test if anticipated benefits are greater than
      anticipated costs. Yet, few studies have investigated the range of financial
      preferences of HIV self-testing (HIVST) among poor men who decline testing or do
      not test regularly. Twenty-three interviews were conducted to qualitatively
      assess perceived costs saved and costs incurred from use of HIVST kits in
      infrequently- or never-tested Tanzanian men. All men were shown an HIVST kit and
      video. They were then asked about the costs associated with provider-led HIV
      testing, financial benefits and concerns of HIVST and willingness to pay for
      HIVST. Data were transcribed, coded and analyzed using inductive content
      analyses. We then grouped codes into perceived cost advantages and disadvantages
      and tabulated the range of prices men were willing to pay for a self-test kit.
      Perceived cost advantages of HIVST were avoidance of spending money to test in
      facilities, omission of follow-up fees, affordability relative to private
      clinics, and increased time for earning income and other activities. Men also
      discussed the imbalance of the financial benefit of accessing free, public HIV
      testing with the resources spent for transport, purchasing meals away from home
      and long wait lines. Perceived cost disadvantages of HIVST were prohibitive kit
      costs, required prior savings to purchase kits, expenditures relating to death
      and preferences for free provider-performed testing. Men were also concerned
      about the psychological costs of inaccurate results. HIVST willingness to pay
      varied among men. Men's decisions to self-test for HIV takes into account
      expected financial gains and losses. Demand generation for HIVST among men should
      consider use of low fees or free HIVST, while emphasizing potential savings from
      reduced travel, clinical costs, or time way from work. Efforts are also needed to
      address anticipated emotional costs of HIVST, such as anxiety from kit errors,
      purchasing "death" or testing alone, which for some men was a substantial
      barrier.

PMID- 29051842
TI  - Is there a Premotor Phase of Essential Tremor?
AB  - BACKGROUND: Essential tremor (ET) is the most common tremor disorder. In addition
      to its hallmark feature, kinetic tremor of the upper limbs, patients may have a
      number of non-motor symptoms and signs (NMS). Several lines of evidence suggest
      that ET is a neurodegenerative disorder and certain NMS may antedate the onset of
      tremor. This article comprehensively reviews the evidence for the existence of a
      "premotor phase" of ET, and discusses plausible biological explanations and
      implications. METHODS: A PubMed search in May 2017 identified articles for this
      review. RESULTS: The existence of a premotor phase of ET gains support primarily
      from longitudinal data. In individuals who develop incident ET, baseline (i.e.,
      premotor) evaluations reveal greater cognitive dysfunction, a faster rate of
      cognitive decline, and the presence of a protective effect of education against
      dementia. In addition, baseline evaluations also reveal more self-reported
      depression, antidepressant medication use, and shorter sleep duration in
      individuals who eventually develop incident ET. In cross-sectional studies,
      certain personality traits and NMS (e.g., olfactory dysfunction) also suggest the
      existence of a premotor phase. DISCUSSION: There is preliminary evidence
      supporting the existence of a premotor phase of ET. The mechanisms are unclear;
      however, the presence of Lewy bodies in some ET brains in autopsy studies and
      involvement of multiple neural networks in ET as evident from the neuroimaging
      studies, are possible contributors. Most evidence is from a longitudinal cohort
      (Neurological Disorders of Central Spain: NEDICES); additional longitudinal
      studies are warranted to gain better insights into the premotor phase of ET.

PMID- 29051843
TI  - Alterations in micro RNA-messenger RNA (miRNA-mRNA) Coupled Signaling Networks in
      Sporadic Alzheimer's Disease (AD) Hippocampal CA1.
AB  - RNA sequencing, DNA microfluidic array, LED-Northern, Western immunoassay and
      bioinformatics analysis have uncovered a small family of up-regulated human brain
      enriched microRNAs (miRNAs) and down-regulated messenger RNAs (mRNAs) in short
      post-mortem interval (PMI) sporadic Alzheimer's disease (AD) brain. At the mRNA
      level, a large majority of the expression of human brain genes found to be down
      regulated in sporadic AD appears to be a consequence of an up-regulation of a
      specific group of NF-kB-inducible microRNAs (miRNAs). This group of up-regulated
      miRNAs - including miRNA-34a and miRNA-146a - has strong, energetically
      favorable, complimentary RNA sequences in the 3' untranslated regions (3'-UTR) of
      their target mRNAs which ultimately drive the down-regulation in the expression
      of certain essential brain genes. Interestingly, just 2 significantly up
      regulated miRNAs - miRNA-34a and miRNA-146a - appear to down-regulate mRNA
      targets involved in synaptogenesis (SHANK3), phagocytosis deficits and tau
      pathology (TREM2), inflammation (CFH; complement factor H) and amyloidogenesis
      (TSPAN12), all of which are distinguishing pathological features characteristic
      of middle-to-late stage AD neuropathology. This paper reports the novel finding
      of parallel miRNA-34a and miRNA-146a up-regulation in sporadic AD hippocampal CA1
      RNA pools and proposes an altered miRNA-mRNA coupled signaling network in AD,
      much of which is supported by current experimental findings in the recent
      literature.

PMID- 29051844
TI  - OCT Angiography: An Upcoming Non-invasive Tool for Diagnosis of Age-related
      Macular Degeneration.
AB  - PURPOSE: To review the most recent findings, characteristics, faults and future
      perspectives of optical coherence tomography angiography (OCTA) in age-related
      macular degeneration (AMD). RECENT FINDINGS: In dry AMD, OCTA is useful on the
      evaluation of choriocapillaris perfusion and detection of naive quiescent non
      exudative choroidal neovascularization (CNV). In wet AMD, OCTA can provide
      detailed anatomic and morphologic information of CNVs, which may help to
      understand why and how they develop and become active. In other hand, the many
      artifacts present in OCTA images may lead to misinterpretation and misdiagnosis.
      SUMMARY: OCTA is a still developing technology that is able to provide a large
      amount of anatomic, functional and morphologic information in macular diseases
      and, particularly, AMD. As the technology evolves, the need of dye-based
      modalities tends to decrease.

PMID- 29051845
TI  - Central Retinal Artery Occlusion: Acute Management and Treatment.
AB  - PURPOSE OF REVIEW: This review will seek to answer if advances in ophthalmic
      imaging and evolution of treatment modalities have shed further light on the
      epidemiology, pathophysiology, diagnosis, and acute management of acute CRAO.
      RECENT FINDINGS: Imaging characteristics of acute CRAO have been further
      characterized with the use of fluorescein angiography, optical coherence
      tomography (OCT), OCT-angiography, and indocyanine-green angiography. Layer
      segmentation of OCT imaging has found inner retinal layer hyper-reflectivity to
      be a common finding in acute CRAO. Non-invasive therapies, fibrinolytic delivery,
      and surgical interventions for acute CRAO have been further evaluated as
      potential management tools. SUMMARY: A large body of literature reports very
      inconsistent treatment success with a wide variety of modalities. Currently,
      there is no clear evidence supporting the use of fibrinolytics in acute CRAO.
      Large, multicenter, randomized control trials are necessary to elucidate the role
      of the various acute treatment options in the management of CRAO.

PMID- 29051846
TI  - Enhanced biodegradation of mixed PAHs by mutated naphthalene 1,2-dioxygenase
      encoded by Pseudomonas putida strain KD6 isolated from petroleum refinery waste.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutant
      that are given top priority to maintain water and soil quality to the most
      amenable standard. Biodegradation of PAHs by bacteria is the convenient option
      for decontamination on site or off site. The aim of the present study was to
      isolate and identify naturally occurring bacteria having mixed PAHs
      biodegradation ability. The newly isolated Pseudomonas putida strain KD6 was
      found to efficiently degrade 97.729% of 1500 mg L-1 mixed PAHs within 12 days in
      carbon-deficient minimal medium (CSM). The half-life (t1/2) and degradation rate
      constant (k) were estimated to be 3.2 and 0.2165 days, respectively. The first
      order kinetic parameters in soil by strain KD6 had shown efficient biodegradation
      potency with the higher concentration of total PAHs (1500 mg kg-1 soil), t1/2 =
      10.44 days-1. However, the biodegradation by un-inoculated control soil was found
      slower (t1/2 = 140 days-1) than the soil inoculated with P. putida strain KD6.
      The enzyme kinetic constants are also in agreement with chemical data obtained
      from the HPLC analysis. In addition, the sequence analysis and molecular docking
      studies showed that the strain KD6 encodes a mutant version of naphthalene 1,2
      dioxygenase which have better Benzpyrene binding energy (-9.90 kcal mol-1) than
      wild type (-8.18 kcal mol-1) enzyme (chain A, 1NDO), respectively, with 0.00 and
      0.08 RMSD values. The mutated naphthalene 1,2-dioxygenase nahAc has six altered
      amino acid residues near to the ligand binding site. The strain KD6 could be a
      good bioresource for in situ or ex situ biodegradation of polycyclic aromatic
      hydrocarbon.

PMID- 29051847
TI  - Symbiotic bacteria associated with puffer fish Gastrophysus spadiceus and
      evaluation of their antimicrobial activities.
AB  - The present study reports the diversity of culturable bacteria associated with
      the puffer fish Gastrophysus spadiceus. During the study, a total of 31 strains
      affiliated to the genera Pseudomonas, Janthinobacterium, Rahnella, and
      Psychrobacter were isolated from liver, intestines, and flesh of G. spadiceus.
      These strains exhibited a diverse range of metabolites as indicated by the HPLC
      and TLC profiles of the chemical extracts of their fermentation products. Some of
      these crude extracts showed strong antimicrobial activities against pathogenic
      bacterial strains. In addition, few crude extracts exhibit insecticidal activity
      against Artemia salina.

PMID- 29051848
TI  - Hydrogenated TiO2 Thin Film for Accelerating Electron Transport in Highly
      Efficient Planar Perovskite Solar Cells.
AB  - Intensive studies on low-temperature deposited electron transport materials have
      been performed to improve the efficiency of n-i-p type planar perovskite solar
      cells to extend their application on plastic and multijunction device
      architectures. Here, a TiO2 film with enhanced conductivity and tailored band
      edge is prepared by magnetron sputtering at room temperature by hydrogen doping
      (HTO), which accelerates the electron extraction from perovskite photoabsorber
      and reduces charge transfer resistance, resulting in an improved short circuit
      current density and fill factor. The HTO film with upward shifted Fermi level
      guarantees a smaller loss on VOC and facilitates the growth of high-quality
      absorber with much larger grains and more uniform size, leading to devices with
      negligible hysteresis. In comparison with the pristine TiO2 prepared without
      hydrogen doping, the HTO-based device exhibits a substantial performance
      enhancement leading to an efficiency of 19.30% and more stabilized photovoltaic
      performance maintaining 93% of its initial value after 300 min continuous
      illumination in the glove box. These properties permit the room-temperature
      magnetron sputtered HTO film as a promising electron transport material for
      flexible and tandem perovskite solar cell in the future.

PMID- 29051849
TI  - Chemically Engineering Magnetic Anisotropy of 2D Metalloporphyrin.
AB  - Continuous miniaturization of magnetic units in spintronics devices inspires
      efforts to search for novel 2D magnetic materials with giant magnetic anisotropy
      energy (MAE). Through systematic first-principles calculations, large MAE of 24
      meV in W or Re embedded 2D polyporphyrin frameworks is found. Interestingly, the
      MAE can be enhanced up to 60 meV, through replacing the hydrogen atoms on the
      edges of the Re based 2D polyporphyrin framework by hydroxyl and amino radicals.
      Analysis of the electronic structures reveals that the enhancement of MAE is
      mainly attributed to charge redistributions and energy shifts of Re 5d orbitals
      induced by the functional radicals. The findings pave a new and feasible way for
      tailoring the magnetic properties of magnetic organic materials to fulfill the
      criteria for applications in spintronics devices at high temperature.

PMID- 29051850
TI  - Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal
      Dosed Cerium Oxide Nanoparticles.
AB  - Spinal cord injury (SCI) produces excess reactive oxygen species (ROS) that can
      exacerbate secondary injury and lead to permanent functional impairment.
      Hypothesizing that cerium oxide nanoparticles (CONPs) as an effective ROS
      scavenger may offset this damaging effect, it is first demonstrated in vitro that
      CONPs suppressed inducible nitric oxide synthase (iNOS) generation and enhanced
      cell viability of hydrogen peroxide (H2O2)-insulted cortical neurons. Next, CONPs
      are administered at various does (50-4000 ug mL-1) to a contused spinal cord rat
      model and monitored the disease progression for up to eight weeks. At one day
      postinjury, the number of iNOS+ cells decreases in the treated groups compared
      with the control. At one week, the cavity size and inflammatory cells are
      substantially reduced, and the expression of proinflammatory and apoptotic
      molecules is downregulated with a concurrent upregulation of anti-inflammatory
      cytokine. By eight weeks, the treated groups show significantly improved
      locomotor functions compared with the control. This study shows for the first
      time that injection of optimal-dosed CONPs alone into contusion-injured spinal
      cord of rats can reduce ROS level, attenuate inflammation and apoptosis, and
      consequently help locomotor functional recovery, adding a promising and
      complementary strategy to the other treatments of acute SCI.

PMID- 29051851
TI  - Biomimetically Engineered Demi-Bacteria Potentiate Vaccination against Cancer.
AB  - Failure in enhancing antigen immunogenicity has limited the development of cancer
      vaccine. Inspired by effective immune responses toward microorganisms, demi
      bacteria (DB) from Bacillus are engineered as carriers for cancer vaccines. The
      explored hydrothermal treatment enables the Bacillus to preserve optimal pathogen
      morphology with intrinsic mannose receptor agonist. Meanwhile, the treated
      Bacillus can be further endowed with ideal hollow/porous structure for efficient
      accommodation of antigen and adjuvant, such as CpG. Therefore, this optimal
      engineered nanoarchitecture allows multiple immunostimulatory elements integrate
      in a pattern closely resembling that of bacterial pathogens. Such pathogen
      mimicry greatly enhances antigen uptake and cross-presentation, resulting in
      stronger immune activation suitable for cancer vaccines. Indeed, DB-based
      biomimetic vaccination in mice induces synergistic cellular and humoral immune
      responses, achieving potent therapeutic and preventive effects against cancer.
      Application of microorganism-sourced materials thus presents new opportunities
      for potent cancer therapy.

PMID- 29051852
TI  - Single Near-Infrared Emissive Polymer Nanoparticles as Versatile
      Phototheranostics.
AB  - Attaining consistently high performance of diagnostic and therapeutic functions
      in one single nanoplatform is of great significance for nanomedicine. This study
      demonstrates the use of donor-acceptor (D-A) structured polymer (TBT) to develop
      a smart "all-five-in-one" theranostic that conveniently integrates
      fluorescence/photoacoustic/thermal imaging and photodynamic/photothermal therapy
      into single nanoparticle. The prepared nanoparticles (TBTPNPs) exhibit near
      infrared emission, high water solubility, excellent light resistance, good pH
      stability, and negligible toxicity. Additionally, the TBTPNPs exhibit an
      excellent singlet oxygen (1O2) quantum yield (40%) and high photothermal
      conversion efficiency (37.1%) under single-laser irradiation (635 nm). Apart from
      their two phototherapeutic modalities, fluorescence, photoacoustic signals, and
      thermal imaging in vivo can be simultaneously achieved because of their enhanced
      permeability and retention effects. This work demonstrates that the prepared
      TBTPNPs are "all-five-in-one" phototheranostic agents that can exhibit properties
      to satisfy the "one-fits-all" requirement for future phototheranostic
      applications. Thus, the prepared TBTPNPs can provide fundamental insights into
      the development of PNP-based nanoagents for cancer therapy.

PMID- 29051853
TI  - Trace-Element Incorporation into Intracellular Pools Uncovers Calcium-Pathways in
      a Coccolithophore.
AB  - Many organisms form minerals from precursor phases that crystallize under strict
      biological control. The dynamic intracellular processes of formation, transport,
      and deposition of these precursor phases are challenging to identify. An unusual
      situation is recently revealed for the calcifying alga Emiliania huxleyi, as the
      cells contain a compartment filled with a concentrated Ca and P phase but the
      final calcite crystals, which are nucleated in a different compartment, are P
      free. Thus, the connection of the Ca-P-rich pool to the mineralization process
      remains unclear. Here, pulse-chase experiments are used with Sr to label the Ca-P
      rich phase in E. huxleyi cells, and cryo X-ray absorption spectroscopy and
      analytical transmission electron microscopy to follow the Sr within cells. It is
      found that Sr is first found in the Ca-P-rich phase and then becomes incorporated
      into the calcite. This demonstrates that the calcium used by the cells to build
      calcite originates from the Ca-P-rich pool.

PMID- 29051854
TI  - An Important Function of Petrosiol E in Inducing the Differentiation of Neuronal
      Progenitors and in Protecting Them against Oxidative Stress.
AB  - Insufficient endogenous neurotrophin supply contributes to neurodegeneration.
      Meanwhile, neuronal injuries are also attributed to oxidative stress upon toxin
      exposure. Thus, reconstruction neurite extension and antioxidative stress are the
      potential strategies for ameliorating neuronal injuries. However, there is no
      well-defined therapeutic developed in this regard. In search of such
      therapeutics, Petrosiol E is identified here as a potent inducer to guide the
      differentiation of neuronal progenitor cells. Petrosiol E also considerably
      promotes embryonic stem cell differentiation into neural ectoderm features.
      Moreover, Petrosiol E reveals an antioxidant function to protect cells from
      oxidative stress induced by arsenic. Moreover, the molecular mechanism underlying
      Petrosiol E-induced neuronal differentiation is uncovered: (a) enhancement of NF
      E2-related factor 2 (Nrf 2) activity in driving neuronal differentiation; (b)
      diminishment of oxidative stress. Petrosiol E activates the mitogen-activated
      protein kinase and serine/threonine kinase signaling to enhance the activity of
      Nrf 2. As a result of enhanced Nrf 2 activity, neuronal differentiation is
      accelerated, and the cellular antioxidation responses are also enforced, even
      under arsenic-induced neurotoxicity. Together, the combined results unveil a
      desirable role of Petrosiol E in driving neuronal differentiation and in
      combating oxidative stress. This study would open an avenue to develop new
      therapeutics based on Petrosiol compounds to treat neurodegenerative diseases.

PMID- 29051855
TI  - Novel Dimethylmethylene-Bridged Triphenylamine-PDI Acceptor for Bulk
      Heterojunction Organic Solar Cells.
AB  - A novel, star-shaped electron acceptor, DMTPA-PDI3, derived from a planar
      dimethylmethylene-bridged triphenylamine core with three acetylene-linked
      perylene diimide (PDI) units is developed as a nonfullerene acceptor for organic
      solar cells (OSCs). DMTPA-PDI3 manifests significantly reduced intramolecular
      twisting, enabling sufficient system-wide pi-electron delocalization leading to
      broadened spectral absorption and raised lowest unoccupied molecular orbital
      level. As a result, higher and more balanced hole and electron transport
      properties are observed. Active layers for OSCs comprising DMTPA-PDI3 acceptor
      and PBT7-Th donor exhibit suppressed intermolecular aggregation, giving rise to
      uniform nanophase network formation. These OSC devices have afforded respectably
      high power-conversion efficiency of about 5%.

PMID- 29051856
TI  - Recent Progress in Graphite Intercalation Compounds for Rechargeable Metal (Li,
      Na, K, Al)-Ion Batteries.
AB  - Lithium-ion batteries (LIBs) with higher energy density are very necessary to
      meet the increasing demand for devices with better performance. With the
      commercial success of lithiated graphite, other graphite intercalation compounds
      (GICs) have also been intensively reported, not only for LIBs, but also for other
      metal (Na, K, Al) ion batteries. In this Progress Report, we briefly review the
      application of GICs as anodes and cathodes in metal (Li, Na, K, Al) ion
      batteries. After a brief introduction on the development history of GICs, the
      electrochemistry of cationic GICs and anionic GICs is summarized. We further
      briefly summarize the use of cationic GICs and anionic GICs in alkali ion
      batteries and the use of anionic GICs in aluminium-ion batteries. Finally, we
      reach some conclusions on the drawbacks, major progress, emerging challenges, and
      some perspectives on the development of GICs for metal (Li, Na, K, Al) ion
      batteries. Further development of GICs for metal (Li, Na, K, Al) ion batteries is
      not only a strong supplement to the commercialized success of lithiated-graphite
      for LIBs, but also an effective strategy to develop diverse high-energy batteries
      for stationary energy storage in the future.

PMID- 29051857
TI  - High-Throughput Inertial Focusing of Micrometer- and Sub-Micrometer-Sized
      Particles Separation.
AB  - The ability to study individual bacteria or subcellular organelles using inertial
      microfluidics is still nascent. This is due, in no small part, to the significant
      challenges associated with concentrating and separating specific sizes of
      micrometer and sub-micrometer bioparticles in a microfluidic format. In this
      study, using a rigid polymeric microfluidic network with optimized microchannel
      geometry dimensions, it is demonstrated that 2 um, and even sub-micrometer,
      particles can be continuously and accurately focused to stable equilibrium
      positions. Suspensions have been processed at flow rates up to 1400 uL min-1 in
      an ultrashort 4 mm working channel length. A wide range of suspension
      concentrations-from 0.01 to 1 v/v%-have been systematically investigated, with
      yields greater than 97%, demonstrating the potential of this technology for large
      scale implementation. Additionally, the ability of this chip to separate
      micrometer- and sub-micrometer-sized particles and to focus bioparticles
      (cyanobacteria) has been demonstrated. This study pushes the microfluidic
      inertial focusing particle range down to sub-micrometer length scales, enabling
      novel routes for investigation of individual microorganisms and subcellular
      organelles.

PMID- 29051858
TI  - Non-Fermi Liquids as Highly Active Oxygen Evolution Reaction Catalysts.
AB  - The oxygen evolution reaction (OER) plays a key role in emerging energy
      conversion technologies such as rechargeable metal-air batteries, and direct
      solar water splitting. Herein, a remarkably low overpotential of ~150 mV at 10 mA
      cm-2disk in alkaline solutions using one of the non-Fermi liquids, Hg2Ru2O7, is
      reported. Hg2Ru2O7 displays a rapid increase in current density and excellent
      durability as an OER catalyst. This outstanding catalytic performance is realized
      through the coexistence of localized d-bands with the metallic state that is
      unique to non-Fermi liquids. The findings indicate that non-Fermi liquids could
      greatly improve the design of highly active OER catalysts.

PMID- 29051859
TI  - Nanoscale Heterogeneity of Multilayered Si Anodes with Embedded Nanoparticle
      Scaffolds for Li-Ion Batteries.
AB  - A new approach on the synthesis of Si anodes for Li-ion batteries is reported,
      combining advantages of both nanoparticulated and continuous Si films. A
      multilayered configuration prototype is proposed, comprising amorphous Si
      arranged in nanostructured, mechanically heterogeneous films, interspersed with
      Ta nanoparticle scaffolds. Particular structural features such as increased
      surface roughness, nanogranularity, and porosity are dictated by the nanoparticle
      scaffolds, boosting the lithiation process due to fast Li diffusion and low
      electrode polarization. Consequently, a remarkable charge/discharge speed is
      reached with the proposed anode, in the order of minutes (1200 mAh g-1 at 10 C).
      Moreover, nanomechanical heterogeneity self-limits the capacity at intermediate
      charge/discharge rates; as a consequence, exceptional cycleability is observed at
      0.5 C, with 100% retention over 200 cycles with 700 mAh g-1. Higher capacity can
      be obtained when the first cycles are performed at 0.2 C, due to the formation of
      microislands, which facilitate the swelling of the active Si. This study
      indicates a method to tune the mechanical, morphological, and electrochemical
      properties of Si electrodes via engineering nanoparticle scaffolds, paving the
      way for a novel design of nanostructured Si electrodes for high-performance
      energy storage devices.

PMID- 29051860
TI  - Correlation between Electronic Defect States Distribution and Device Performance
      of Perovskite Solar Cells.
AB  - In the present study, random current fluctuations measured at different
      temperatures and for different illumination levels are used to understand the
      charge carrier kinetics in methylammonium lead iodide CH3NH3PbI3-based perovskite
      solar cells. A model, combining trapping/detrapping, recombination mechanisms,
      and electron-phonon scattering, is formulated evidencing how the presence of
      shallow and deeper band tail states influences the solar cell recombination
      losses. At low temperatures, the observed cascade capture process indicates that
      the trapping of the charge carriers by shallow defects is phonon assisted
      directly followed by their recombination. By increasing the temperature, a phase
      modification of the CH3NH3PbI3 absorber layer occurs and for temperatures above
      the phase transition at about 160 K the capture of the charge carrier takes place
      in two steps. The electron is first captured by a shallow defect and then it can
      be either emitted or thermalize down to a deeper band tail state and recombines
      subsequently. This result reveals that in perovskite solar cells the
      recombination kinetics is strongly influenced by the electron-phonon
      interactions. A clear correlation between the morphological structure of the
      perovskite grains, the energy disorder of the defect states, and the device
      performance is demonstrated.

PMID- 29051861
TI  - Additive Manufacturing: Unlocking the Evolution of Energy Materials.
AB  - The global energy infrastructure is undergoing a drastic transformation towards
      renewable energy, posing huge challenges on the energy materials research,
      development and manufacturing. Additive manufacturing has shown its promise to
      change the way how future energy system can be designed and delivered. It offers
      capability in manufacturing complex 3D structures, with near-complete design
      freedom and high sustainability due to minimal use of materials and toxic
      chemicals. Recent literatures have reported that additive manufacturing could
      unlock the evolution of energy materials and chemistries with unprecedented
      performance in the way that could never be achieved by conventional manufacturing
      techniques. This comprehensive review will fill the gap in communicating on
      recent breakthroughs in additive manufacturing for energy material and device
      applications. It will underpin the discoveries on what 3D functional energy
      structures can be created without design constraints, which bespoke energy
      materials could be additively manufactured with customised solutions, and how the
      additively manufactured devices could be integrated into energy systems. This
      review will also highlight emerging and important applications in energy additive
      manufacturing, including fuel cells, batteries, hydrogen, solar cell as well as
      carbon capture and storage.

PMID- 29051863
TI  - High-Performance Lithium-Oxygen Battery Electrolyte Derived from Optimum
      Combination of Solvent and Lithium Salt.
AB  - To fabricate a sustainable lithium-oxygen (Li-O2) battery, it is crucial to
      identify an optimum electrolyte. Herein, it is found that tetramethylene sulfone
      (TMS) and lithium nitrate (LiNO3) form the optimum electrolyte, which greatly
      reduces the overpotential at charge, exhibits superior oxygen efficiency, and
      allows stable cycling for 100 cycles. Linear sweep voltammetry (LSV) and
      differential electrochemical mass spectrometry (DEMS) analyses reveal that neat
      TMS is stable to oxidative decomposition and exhibit good compatibility with a
      lithium metal. But, when TMS is combined with typical lithium salts, its
      performance is far from satisfactory. However, the TMS electrolyte containing
      LiNO3 exhibits a very low overpotential, which minimizes the side reactions and
      shows high oxygen efficiency. LSV-DEMS study confirms that the TMS-LiNO3
      electrolyte efficiently produces NO2-, which initiates a redox shuttle reaction.
      Interestingly, this NO2-/NO2 redox reaction derived from the LiNO3 salt is not
      very effective in solvents other than TMS. Compared with other common Li-O2
      solvents, TMS seems optimum solvent for the efficient use of LiNO3 salt. Good
      compatibility with lithium metal, high dielectric constant, and low donicity of
      TMS are considered to be highly favorable to an efficient NO2-/NO2 redox
      reaction, which results in a high-performance Li-O2 battery.

PMID- 29051862
TI  - Recent Advances in Designing and Fabricating Self-Supported Nanoelectrodes for
      Supercapacitors.
AB  - Owing to the outstanding advantages as electrical energy storage system,
      supercapacitors have attracted tremendous research interests over the past
      decade. Current research efforts are being devoted to improve the energy storage
      capabilities of supercapacitors through either discovering novel electroactive
      materials or nanostructuring existing electroactive materials. From the device
      point of view, the energy storage performance of supercapacitor not only depends
      on the electroactive materials themselves, but importantly, relies on the
      structure of electrode whether it allows the electroactive materials to reach
      their full potentials for energy storage. With respect to utilizing
      nanostructured electroactive materials, the key issue is to retain all advantages
      of the nanoscale features for supercapacitors when being assembled into
      electrodes and the following devices. Rational design and fabrication of self
      supported nanoelectrodes is therefore considered as the most promising strategy
      to address this challenge. In this review, we summarize the recent advances in
      designing and fabricating self-supported nanoelectrodes for supercapacitors
      towards high energy storage capability. Self-supported homogeneous and
      heterogeneous nanoelectrodes in the forms of one-dimensional (1D) nanoarrays, two
      dimensional (2D) nanoarrays, and three-dimensional (3D) nanoporous architectures
      are introduced with their representative results presented. The challenges and
      perspectives in this field are also discussed.

PMID- 29051864
TI  - Formation of Single-Holed Cobalt/N-Doped Carbon Hollow Particles with Enhanced
      Electrocatalytic Activity toward Oxygen Reduction Reaction in Alkaline Media.
AB  - Design and construction of metal-organic framework (MOF) composite precursors
      have recently been considered as a promising strategy for the preparation of
      different structured metal/carbon-based functional materials. Here, an MOF
      composite-assisted strategy to synthesize single-holed cobalt/N-doped carbon
      hollow particles is reported. The yolk-shell polystyrene@zeolitic imidazolate
      framework-67 (PS@ZIF-67) composite precursors are first synthesized, followed by
      a controlled pyrolysis to obtain cobalt/N-doped carbon hollow particles with a
      large single hole on each shell. Moreover, the MOF-coating approach reported in
      this work can be extended to prepare various core-shell ZIF-67 composites with
      different structures and compositions. Benefiting from the structural and
      compositional advantages, the as-derived single-holed cobalt/N-doped carbon
      hollow particles manifest superior electrocatalytic oxygen reduction performance
      with high activity and excellent durability.

PMID- 29051865
TI  - Photothermal Catalyst Engineering: Hydrogenation of Gaseous CO2 with High
      Activity and Tailored Selectivity.
AB  - This study has designed and implemented a library of hetero-nanostructured
      catalysts, denoted as Pd@Nb2O5, comprised of size-controlled Pd nanocrystals
      interfaced with Nb2O5 nanorods. This study also demonstrates that the catalytic
      activity and selectivity of CO2 reduction to CO and CH4 products can be
      systematically tailored by varying the size of the Pd nanocrystals supported on
      the Nb2O5 nanorods. Using large Pd nanocrystals, this study achieves CO and CH4
      production rates as high as 0.75 and 0.11 mol h-1 gPd-1, respectively. By
      contrast, using small Pd nanocrystals, a CO production rate surpassing 18.8 mol h
      1 gPd-1 is observed with 99.5% CO selectivity. These performance metrics
      establish a new milestone in the champion league of catalytic nanomaterials that
      can enable solar-powered gas-phase heterogeneous CO2 reduction. The remarkable
      control over the catalytic performance of Pd@Nb2O5 is demonstrated to stem from a
      combination of photothermal, electronic and size effects, which is rationally
      tunable through nanochemistry.

PMID- 29051867
TI  - Patient Centric Orthopaedics, Patient Oriented Research and Concept of
      Clinicothesis.

PMID- 29051866
TI  - Mechanisms navigating the TGF-beta pathway in prostate cancer.
AB  - Few pharmacotherapies are currently available to treat castration resistant
      prostate cancer (CRPC), with low impact on patient survival. Transforming growth
      factor-beta (TGF-beta) is a multi-functional peptide with opposite roles in
      prostate tumorigenesis as an inhibitor in normal growth and early stage disease
      and a promoter in advanced prostate cancer. Dysregulated TGF-beta signaling leads
      to a cascade of events contributing to oncogenesis, including up-regulated
      proliferation, decreased apoptosis, epithelial-to-mesenchymal transition (EMT)
      and evasion of immune surveillance. TGF-beta signaling pathway presents an
      appropriate venue for establishing a therapeutic targeting platform in CRPC.
      Exploitation of TGF-beta effectors and their cross talk with the androgen axis
      pathway will provide new insights into mechanisms of resistance of the current
      antiandrogen therapeutic strategies and lead to generation of new effective
      treatment modalities for CRPC. Points of functional convergence of TGF-beta with
      key oncogenic pathways, including mitogen-activated protein kinase (MAPK) and
      androgen receptor (AR), are discussed as navigated within the EMT landscape in
      the tumor microenvironment. In this context the emerging anti-TGF-beta
      pharmacotherapies for prostate cancer treatment are considered. Targeting the
      functional cross-talk between the TGF-beta signaling effectors with the androgen
      axis supports the development of novel therapeutic strategies for treating CRPC
      with high specificity and efficacy in a personalized-medicine approach.

PMID- 29051868
TI  - Minimally Invasive Joint Replacement Surgery: Where Are We Now?

PMID- 29051869
TI  - Case of Acute Concomitant Rupture of Anterior Cruciate Ligament and Patellar
      Tendon of Knee: Surgical Decision Making and Outcome.
AB  - INTRODUCTION: Acute concomitant rupture of both anterior cruciate ligament (ACL)
      and patellar tendon is a rare injury. The diagnosis of either of the injuries may
      be missed on clinical examination in the emergency room. A high index of
      suspicion is necessary when active extension is absent, and necessary
      investigations like ultrasound or magnetic resonance imaging (MRI) should be done
      to confirm the diagnosis. There are no fixed treatment protocols in these
      injuries. The options include immediate repair of patellar tendon with either
      simultaneous or delayed reconstruction of ACL. CASE REPORT: We present a case of
      30-year-old man with simultaneous ACL and patellar tendon injury sustained in a
      RTA, riding pillion on a bike. The mechanism of injury was a direct blow on his
      flexed right knee followed by landing on the ground, on his foot with a twisting
      valgus thrust. Following clinical examination and radiographs, MRI was done which
      showed complete patellar tendon mid substance rupture and ACL tear. A staged
      procedure was planned, and the patient was taken up for immediate patellar tendon
      repair. This was followed by 5 weeks of cast immobilization. After 6 weeks, the
      knee was mobilized and ACL reconstruction was done using hamstring graft. At
      last, follow-up, the patient regained full knee extension and flexion up to 120
      degrees  with normal gait. CONCLUSION: High-velocity knee injuries have to be
      carefully evaluated for such concomitant tears, as they may be missed. If
      suspected, an immediate ultrasound scan or MRI should be done to confirm the
      injuries, especially that of the patellar tendon. As of now, a staged procedure
      comprising immediate patellar tendon repair followed by ACL reconstruction at a
      later date seems to be the better option of treatment.

PMID- 29051870
TI  - An Unusual Case Report of Bertolotti's Syndrome: Extraforaminal Stenosis and L5
      Unilateral Root Compression (Castellvi Type III an LSTV).
AB  - INTRODUCTION: Castellvi Type III lumbosacral transitional vertebrae (LSTV) is an
      unusual case of Bertolotti's syndrome (BS) due to extraforaminal stenosis,
      especially manifesting in elderly patients. CASE REPORT: We report a case of BS
      in a 62 years old Greek female. The signs of the clinical examination are low
      back pain, sciatica, hypoesthesia, and pain to the contribution of L5 nerve.
      Imaging techniques revealed an LSTV Type III a (complete sacralization between
      LSTV and sacrum). CONCLUSION: Despite the fact that LSTV is a congenital lesion,
      the clinical manifestation of BS may present in the elderly population. The
      accumulative effect of the gradual degeneration of intervertebral foramen
      (stenosis) may lead to the compression of extraforaminal portion of the nerve
      root.

PMID- 29051871
TI  - Bilateral Divergent Shoulder's Fracture Dislocation Case in an Ischemic Stroke
      Patient.
AB  - INTRODUCTION: The literature review revealed that nowadays only about 15 cases of
      bilateral shoulder dislocation associated with the fracture of the upper end of
      the humerus have been published. The triad of lesional mechanism designated by
      the triple syndrome E composed of epilepsy, electrocution, and external trauma
      was the circumstances noted in which these fractures dislocations occur with
      migration of the two humeral heads either forward or backward. CASE REPORT: An
      architect of 36-year-old, right-handed, was admitted in emergency department for
      loss of knowledge of progressive installation. At admission the blood pressure,
      pulse, and temperature were normal. There was a right hemiparesis predominantly
      in brachiofacial side and an aphasia. After intensive resuscitation measures, the
      cerebral computed tomography scan revealed a left temporoparietal hypodensity
      area affecting the middle cerebral artery superficial territory with a mass
      effect compatible with acute ischemic stroke. During the hospitalization,
      episodes of generalized tonic-clonic convulsions appeared with a fever at 39
      degrees C and a leukocytosis at 35 thousand on the 5th day. These convulsions
      caused on the right shoulder an anterior dislocation under coracoid, associated
      with a fracture of the greater tubercle and on the left shoulder, posterior
      dislocation with much displaced comminuted articular proximal humeral fracture.
      We did reduction by external maneuvers for the right shoulder and open reduction
      with internal fixation by anatomical plate of left shoulder lesions. In the
      immediate aftermath of surgery, he presented episodes of agitation which led to
      the dismantling of the left shoulder fixation. He was evacuated to the North
      Country where an ablation of the left shoulder material and stabilization by
      locked plate were carried out. The sequelae were marked by the occurrence of an
      osteomyelitis with osteolysis of the entire upper right humerus extremity. It
      will require an inverted prosthesis. CONCLUSION: The surgical treatment must be
      done by a solid assembly and consultation with neurologists and anesthetists is
      essential. This multidisciplinary management could prevent any convulsive
      postoperative seizures that would risk sacrificing all therapeutic efforts.

PMID- 29051872
TI  - Synovial Hemangioma of the Knee Management and Excellent Outcome 2 Years after
      Arthroscopic Synovectomy in a 25-year-old Male with a 20-year History.
AB  - INTRODUCTION: Synovial hemangioma is a rare condition with <200 published case
      reports in world literature and is frequently misdiagnosed, leading to diagnostic
      delay of many years. This delay is even more significant if the patient comes
      from a rural background with a dearth of medical facilities in the area. This
      case had a lag of nearly 20 years from the time of onset of symptoms and the
      required management which is the maximum reported for any synovial hemangioma
      since most of them have been found and treated in adolescents. CASE REPORT: We
      present a case of an atypical synovial hemangioma in a 25-year-old Indian male
      from a poor socioeconomic background with a delay of 20 years who had both
      recurrent knee effusions and long-standing knee pain but kept ignoring his
      symptoms. It was managed by arthroscopic synovectomy. The patient reported to us
      after 2 years after the surgery with a painless knee and full range of movement.
      CONCLUSION: Synovial hemangioma mostly affects the knee joint, showing recurrent
      bloody effusions without a history of trauma. If there are no intermittent
      effusions, the diagnosis will be even more difficult. In cases of non-specific
      symptoms and long-standing knee pain of many years, the diagnosis of a synovial
      hemangioma should also be considered. In this particular case, magnetic resonance
      imaging was used to evaluate the patient after the plain radiographs and showed
      characteristic lace-like or linear patterns. Diagnostic arthroscopy and surgical
      excision were done in the same sitting, and biopsy was sent to the histopathology
      laboratory which confirmed our diagnosis. Although this patient had the disease
      since 20 years and presented late, he had little degeneration of cartilage at the
      time of arthroscopy. The functional outcome at 2-year follow-up was excellent,
      and he had no disability, effusion and was pain free.

PMID- 29051873
TI  - Median Nerve Entrapment after Elbow Dislocation and the Role of Ultrasonography -
      A Case Report.
AB  - INTRODUCTION: Median nerve entrapment in the cases of posterior dislocation of
      elbow is a rare entity. The diagnosis is usually delayed. We describe here a case
      of median nerve entrapment in the posteromedial dislocation of elbow in a 10-year
      old male child and the role of ultrasonography (USG) in localizing the median
      nerve in the elbow. The nerve release was done by osteotomy of medial epicondyle.
      USG thus proved to be a useful tool in the management of nerve injury. CASE
      REPORT: The authors present here a case of 10-year-old child with a history of
      dislocation of right elbow that was reduced elsewhere and the child presented to
      us with stiffness and restriction of movements at the elbow with the features of
      high median nerve injury. On further evaluation with ultrasound, the median nerve
      was found to be entrapped in the elbow behind the medial epicondyle. Medial
      condyle osteotomy was done to release the median nerve and to provide the relief
      of symptoms. CONCLUSION: Median nerve entrapment after the elbow dislocation is a
      very rare entity. High index of suspicion and the ultrasound are quite helpful in
      arriving at the diagnosis of this rare clinical entity. Timed surgical release of
      the nerve and can provide good function.

PMID- 29051874
TI  - Hamulus Stress Fracture in a Batsman: An Unusual Injury in Cricket - A Case
      report and Review of Literature.
AB  - INTRODUCTION: Hamulus fractures are uncommon injuries constituting 2-4% of carpal
      fractures and are usually reported in athletes. Stress fractures of hamulus are
      even rarer and very few cases have been reported till date. In this case report,
      we present the first documented case of stress fracture of hamulus in a cricket
      batsman and review the existing literature on hamulus fractures, both acute and
      stress fractures, in sportspersons in general. CASE REPORT: A 23-year-old, right
      handed, cricket batsman presented with pain in the hypothenar region of his left
      hand of 7 weeks duration. The pain typically worsened during batting, and he had
      difficulty in gripping the bat. Plain radiographs were largely inconclusive;
      magnetic resonance images, however, demonstrated a stress fracture of the hamate
      hook. The patient was put on conservative management, and his bat grip was
      modified. He recovered completely within 12 weeks and went back to playing
      professional cricket. CONCLUSIONS: Hamulus stress fractures should be considered
      in cricketers presenting with chronic, non-traumatic, and ulnar-sided hand pain.
      The nonleading hand is more likely to be involved in a batter, as seen in other
      sports with a double haSnd grip. Nonoperative treatment, change of grip and
      adequate rehabilitation give good outcomes in most cases.

PMID- 29051875
TI  - Undisplaced Intraoperative Fracture Presenting as Early Dislocation with Tapered
      Wedge Stems in Total Hip Arthroplasty - Case Series and Review of Literature.
AB  - INTRODUCTION: Periprosthetic fractures and dislocation in the early post
      operative period can be disastrous both for the surgeon and the patient. However,
      undisplaced periprosthetic fractures presenting with dislocation is uncommon. We
      describe successful management of two cases (one bilateral dislocation and one
      unilateral dislocation) of undisplaced iatrogenic fractures in total hip
      arthroplasty (THA) presenting as early dislocation. CASE REPORT: Case 1 was a 45
      year-old female with osteoarthritis of hip secondary to developmental dysplasia
      of the hip with bilateral early nontraumatic dislocation with bilateral identical
      periprosthetic fracture. It was managed by revision to long stem and encirclage
      wiring. Case 2 presented with early dislocation in the 2nd week post THA. We
      found an intertrochanteric fracture intra-operatively with unstable implant.
      Acetabular component and femoral component revision were done with reconstruction
      of the greater trochanter. DISCUSSION: These fractures could be occult iatrogenic
      fractures characteristic of taper wedge stems which presented as early
      nontraumatic dislocation in the post-operative period. The prosthesis subsidence,
      loss of muscle tension and change of version might be the factors leading to
      dislocation. CONCLUSION: Unrecognized incomplete intraoperative fracture can
      occur with tapered wedge uncemented stems which can present as a dislocation in
      the immediate post-operative period. This will require early revision of the
      femoral component.

PMID- 29051876
TI  - Transient Migratory Osteoporosis of the Hip and Talus: A Case Report.
AB  - INTRODUCTION: Transient migratory osteoporosis (TMO) is a rare and self-limiting
      condition of unknown etiology. The hip joint is the most common joint to get
      involved in this disease followed by a knee, ankle, and foot. CASE REPORT: We
      report a case, which illustrates the importance of recognizing the typical
      clinical and radiological features of TMO of the hip and ankle, thereby allowing
      an appropriate form of treatment. Spontaneous resolution of symptoms occurred in
      the patient. CONCLUSION: TMO can present a diagnostic challenge, but awareness of
      the typical presenting features and investigation findings can often avoid
      diagnostic difficulties.

PMID- 29051877
TI  - A Case of Non-Traumatic Avascular Necrosis of Femur in Case of Transfusion
      Dependent Thalassemia.
AB  - INTRODUCTION: Avascular necrosis of the head of femur (AVNF) has frequently been
      reported with sickle cell anemia but is not commonly associated with beta
      thalassemia. CASE REPORT: We report a case of 14-year-old male with transfusion
      dependent thalassemia (TDT) and hepatitis C, who developed bilateral atraumatic
      AVNF requiring surgical correction. The likely etiopathogenesis and the review of
      literature for this uncommon finding are discussed. CONCLUSION: AVNF should be
      considered as a possibility in a patient with TDT presenting with hip pain.
      Multiple disease and treatment related factors are likely to play a key role in
      its causation.

PMID- 29051878
TI  - Patellofemoral Articulating Osteochondral (Kissing) Lesion Treated with
      Autologous Chondrocyte Implantation: A Case Report.
AB  - INTRODUCTION: Autologous chondrocyte implantation (ACI) is an effective treatment
      for chondral defects of the knee; however, its use in kissing lesions is less
      well documented. CASE REPORT: A 23-year-old female with a kissing lesion of the
      patellofemoral compartment on magnetic resonance imaging underwent two-stage ACI
      to her medial patella (20 mm * 22 mm) and medial trochlea (27 mm * 18 mm). At 1
      year follow-up, the patient had returned to all activities with near-complete
      resolution of symptoms and substantial improvement in clinical outcome scores.
      CONCLUSION: Patients with kissing lesions of the knee can be treated successfully
      with ACI performed to multiple sites.

PMID- 29051879
TI  - The Destructive Power of Circumstance on Concurrent Poliomyelitis and
      Osteomyelitis.
AB  - INTRODUCTION: The current method in dealing with pediatric hip pathologies is to
      avoid joint replacement unless absolutely necessary. This decision is typically
      made on a scientific basis. However, this is not necessarily the correct approach
      in all cases as demonstrated in the following case report where social issues is
      an extremely important variable to be considered when deciding on surgical
      intervention. CASE REPORT: This case report is the first of its kind to highlight
      the pathology mentioned and the social determinants that were a causative agent
      in its development. This case revolves around a 46-year-old Caucasian gentleman
      who presented in clinic enquiring about the possibility of a hip arthroplasty. He
      aimed to improve his ability to work after the cessation of state benefits. A
      retrospective look at his history indicated a number of social factors lead to
      poor outcomes and the resulting downward spiral causing his current presentation.
      The effect of social circumstances on the medical and surgical outcomes is
      highlighted in this report with a look into avascular necrosis and resulting
      natural arthrodesis. Both of these presentations were secondary to chronic and
      untreated childhood osteomyelitis of the right hip in conjunction with
      poliomyelitis development. The dual involvement of poliomyelitis and
      osteomyelitis to the hip joint no doubt had a massive impact on final pathology
      and is a rarely documented phenomenon. From an early age, this patient has faced
      difficulties integrating in society by factors that were out of his control. By
      the time he was old enough to lead an independent life, the damage had been
      inflicted both medically and psychologically through his earlier ordeals.
      CONCLUSION: By writing this up, it is hoped that clinicians will recognize the
      debilitating holistic effect that mechanical joint pathologies and neurological
      deficiencies can have on patients' lives with the view to reopen the discussion
      on when it is appropriate to surgically intervene in hip pathologies in children
      and especially where osteomyelitis and poliomyelitis are involved.

PMID- 29051880
TI  - An Exceptional Case of Suture Granuloma 30 Years Following an Open Repair of
      Achilles Tendon Rupture: A Case Report.
AB  - INTRODUCTION: Rupture of the Achilles' tendon is a common injury occurring
      particularly in middle-aged men due to sports trauma. Operative treatment is
      preferred generally due to lower risk of re-rupture. Possible complications of
      the operation include suture granulomas. Suture granulomas might represent a
      foreign body reaction, which itself is the end-stage response of the inflammatory
      wound-healing process to biomaterials. It may occur with both absorbable and non
      absorbable suture materials such as silk in our case. The aim of this study is to
      present a case of a delayed foreign body reaction 30 years after open repair of
      the Achilles tendon with silk sutures. CASE REPORT: Our case is a 38-year-old
      male who presented to our outpatient clinic with complaints of swelling and pain
      around the posterior region of the ankle for the past 3 months. He had a history
      of open Achilles tendon repair at the age of 3 at the site of complaints.
      Physical examination was positive for a mass under the incision scar. Magnetic
      resonance imaging report was positive for a granulomatosis formation. The patient
      was booked for an operation to remove the mass. CONCLUSION: Suture granuloma
      represents a tissue reaction against the suture material. Orthopedic literature
      is sparse for such cases and case reports. Both because of its rarity in
      orthopedic literature and the amount of time between the surgery and reaction,
      our report is a valuable addition to the literature.

PMID- 29051881
TI  - Fracture Management in Pyknodysostosis - A Rare Case Report.
AB  - INTRODUCTION: Pyknodysostosis is congenital osteosclerotic skeletal dysplasia of
      a rare entity. It is an autosomal recessive disease which presents with short
      stature and generalized osteosclerosis of skeleton as result of decreased bone
      turnover. Here, the authors report a case of pyknodysostosis who presented to our
      emergency room with a pathological fracture in the shaft of the femur for which
      operative intervention was carried out. CASE REPORT: A 30-year-old female
      presented to our emergency room with a history of trivial injury to right thigh
      region and was diagnosed as fracture in her right femur shaft region. After a
      detailed clinical, radiological, and blood investigations, the patient was taken
      up for operative modality of intervention in the form of plate osteosynthesis. As
      the medullary canal was narrow and bone was osteosclerotic, the option of closed
      intramedullary interlocking nailing was ruled out. Hence, we proceeded with open
      reduction and internal fixation with plate osteosynthesis using a board dynamic
      compression plate. Post-operative period was uneventful. Patient underwent non
      weight bearing mobilization for 2 months. At 10-week post-operative follow-up,
      the patient presented with pain over surgical site and radiological examination
      showed no signs of union. The patient underwent additional plating augmented with
      bone grafting using grafts harvested from iliac crest and synthetic bone graft.
      The patient developed deep-seated infection immediate post-operative period for
      which she was treated with wound debridement, and appropriate intravenous
      antibiotics were given 2 weeks and orally for 4 weeks. At 6-month follow-up, the
      patient is able to carry her day-to-day activity with complete recovery and
      radiological signs of union. The patient had classical clinical features
      suggestive of pyknodysostosis. Patient has 2 siblings of same family (one brother
      and sister) with similar clinical and radiological features. CONCLUSION:
      Recognition of these clinical and radiological signs is important to make the
      diagnosis of pyknodysostosis and prevent possible complications. Additional care
      must be taken in treating these patients.

PMID- 29051882
TI  - Osteomyelitis of Fibula Rare Case with Various Differential Diagnosis.
AB  - INTRODUCTION: The osteomyelitis of fibula is a rare case to present.
      Osteomyelitis is clinical diagnosis with support of various investigation with
      proper surgical technique and various Differential Diagnosis it is treated with
      good satisfactory result. CASE REPORT: A 65-year-male operated 10 years back for
      tibial plateau fracture was asymptomatic but for last 3 months started pus
      discharging sinus from middle third of leg. We investigated and done implant
      removal with abnormal tissue abnormal bone was excised out, but very unusual
      presentation intraoperative necrotic massive debris was there like wood pieces
      mimic as neoplastic lesion, metastasis, fungal osteomyelitis, or granulomatous
      infection. However, after biopsy, it was diagnosed pyogenic osteomyelitis 2 weeks
      of injectable and 6 weeks of oral antibiotics were given. After that 4-6 weeks
      weight bearing was started, the patient returned to his obvious activities with
      normal range of motion. CONCLUSION: The osteomyelitis of fibula with various
      differential diagnosis clinically and intraoperatively with very rare necrotic
      tissues like wood pieces mimicked neoplasia fungal infection but after proper
      debridement curettage and biopsy report probable diagnosis is made with proper
      duration of antibiotic treatment chronic osteomyelitis is treated with
      satisfactory result with good outcome.

PMID- 29051883
TI  - Early Motor Delay: An Outstanding, Initial Sign of Osteogenesis Imperfecta Type
      1.
AB  - INTRODUCTION: Osteogenesis imperfect (OI) is a heterogeneous and complex
      connective tissue disorder that manifests with low bone density and fragility.
      More than 15 types of OI have been distinguished on a clinical and molecular
      basis, but the classical clinical classification previously proposed in Types 1-4
      with the recent inclusion of Type 5 appears to be more suitable. The diagnosis is
      mainly made on clinical and radiographic findings with fractures caused by mild
      trauma, bowing deformities of long bones, and growth deficiency. Non-skeletal
      features of the disorder include blue sclerae, hearing loss, decreased pulmonary
      function, cardiac valvular regurgitation, and muscle weakness. CASE REPORT: We
      report on a toddler girl affected by OI Type 1 who suffered from marked muscle
      weakness as the first initial sign, which led us to follow the diagnostic
      checklist for hypotonic children. The typical signs of the disorder later became
      evident and consistent with this diagnosis, including bone fractures and blue
      sclerae. CONCLUSION: Early muscle weakness, previously unreported sign, may be an
      initial manifestation of OI, to be included in the differential diagnosis of
      disorders that cause hypotonia in childhood.

PMID- 29051884
TI  - Curettage Using Soft-wire for Enchondroma in the Hand: A Technical Note.
AB  - INTRODUCTION: Enchondromas are benign bone cartilaginous lesions predominantly
      seen in the hand, possibly leading to a pathological fracture. When the lesion
      expands to the whole phalanx, curettage through a small fenestration is
      difficult. To overcome the problem, soft-wire (cerclage wire) was used as a
      curette. Soft-wire is commonly used for a tension band wiring method for patellar
      or olecranon fractures. TECHNIQUE: Two representative cases are presented: one is
      a 43-year-old male with enchondroma in the middle phalanx of the left index
      finger, and the other is a 28-year-old female with enchondroma in the distal
      phalanx of the right thumb. Surgery was performed in both cases under general
      anesthesia. The cortex adjacent to the lesion was approached dorsally, splitting
      the extensor tendon (the index finger case), or laterally (the thumb case).
      Fenestration of the cortex was performed with a 3.2-4 mm diameter surgical air
      drill. A bent and looped soft-wire of 0.7 or 0.9 mm diameter was threaded through
      the fenestration and used as a curette. Consequently, beta-tricalcium phosphate
      particles were implanted. Bone incorporation was observed. CONCLUSION: This easy
      technique of curettage is a minimally invasive procedure for enchondroma.
      Moreover, the length of the skin incision and the size of the cortical
      fenestration are the same regardless of the size of the lesion.

PMID- 29051885
TI  - The Reversed Less Invasive Stabilisation System-Distal Femur Technique:
      Application in an Adult Patient with Osteogenesis Imperfecta Sustaining a Femoral
      Fracture.
AB  - INTRODUCTION: The aim of this study was to report the surgical management and to
      discuss the options for fracture fixation in an adult patient with osteogenesis
      imperfecta (OI) who sustained a trochanteric femoral fracture after a simple fall
      from standing position. CASE REPORT: As a result of multiple fractures during
      childhood, this adult patient with OI presented with a short stature. The
      radiographs revealed a displaced, intertrochanteric fracture with subtrochanteric
      extension of the left femur. The intramedullary canal was narrow, the femur
      presented with a severe bowing deformity, and the bone quality was poor. The
      implant of choice was plating using the reversed less invasive stabilisation
      system-distal femur (LISS-DF) technique. This technique was introduced for the
      management of subtrochanteric fractures in the elderly with poor bone stock. In
      addition, a locking plate attached to the LISS-DF allowed for additional screw
      placement at the apex of the curvature of the femur although the plate was not in
      line with the femur at this site. Cerclages were used for metaphyseal reduction
      and fixation. 4-month postoperatively, the patient was ambulatory without any
      assistance with full weight bearing. At the latest follow-up 1-year
      postoperatively, the patient was still free of complaints and at her preinjury
      activity level. CONCLUSION: The presented technique was successful as a salvage
      procedure in a rare case of adult OI presenting with a femoral fracture with
      characteristics influencing the decision-making in treatment options.

PMID- 29051886
TI  - Longest Known Follow-up of a Hip Arthroplasty: The Last Chapter of a 65-Year Long
      Story.
AB  - INTRODUCTION: The Smith-Petersen vitallium mold arthroplasty was a real landmark
      in arthroplasty surgery as this was the first technique which produced
      predictable and satisfactory results. CASE REPORT: We present the longest known
      follow-up of any hip arthroplasty in literature. The arthroplasty was performed
      in 1949 in London on a 30-years-old female patient with congenital hip dysplasia,
      and it was revised in 2014 after 65 years. CONCLUSION: Total hip arthroplasties
      nowadays give better functional results, but the fact that the patient got 65
      years of the relatively good function is noteworthy and is a tribute to Dr.
      Marius Nygaard Smith-Petersen.

PMID- 29051887
TI  - Uncommon Floating Knee in a Teenager: A Case Report of Ipsilateral Physeal
      Fractures in Distal Femur and Proximal Tibia.
AB  - INTRODUCTION: The concomitance of ipsilateral physeal fractures of the distal
      femur and the proximal tibia is an extremely scarce entity. It is conceptually
      similar to floating knee in pediatric population. CASE REPORT: One case with this
      injury is reported in a 16-year-old teenager. He was treated surgically by close
      reduction and internal fixation. The diagnosis of the tibial fracture was
      initially missed and the fracture was seen on the post-operative radiographs.
      Orthopedic treatment was made for this injury. 2 years after, no angular
      deformity neither shortening of the limb were found. CONCLUSION: These rare
      injuries could have serious immediate and remote complication with a considerable
      functional impact. The diagnosis of proximal tibia physeal fracture could be
      missed in the context of a concomitant more impressive distal femur fracture. The
      possibility of a combination of these two injuries should then be kept in mind.
      Anatomic reduction should be made as soon as possible using a gentle technique
      and attention should be given to the diagnosis of the neurovascular
      complications.

PMID- 29051888
TI  - Triplane Ankle Fracture with Concomitant Ipsilateral Shaft of Tibia Fracture:
      Case Report and Review of Literature.
AB  - INTRODUCTION: Triplane fracture is a rare adolescent ankle injury. Its
      association with ipsilateral tibial shaft fracture is very rarely reported in the
      literature. CASE REPORT: This is a case of a 14-year-old male who sustained a
      twisting injury to his right leg after a fall from a height. He sustained a
      minimally displaced spiral fracture of the mid-shaft of his right tibia with a
      concomitant ipsilateral two part triplane fracture of the ankle. He underwent
      minimally invasive percutaneous locking plate fixation for tibial fracture and
      percutaneous screw fixation for an ankle fracture. Both fractures healed
      uneventfully in 10 weeks with complete functional recovery in 12 weeks.
      CONCLUSION: The ankle injury, in such cases, can easily be missed in the presence
      of the more obvious tibial fracture and emergency physicians should also be aware
      of such injuries. As this injury is peculiar to the adolescent age group, we
      recommend ankle assessment of all patients with tibial shaft fractures in this
      age group.

PMID- 29051889
TI  - Supraclavicular Approach to Ultrasound-Guided Brachiocephalic Vein Cannulation in
      Children and Neonates.
AB  - The correct choice of intra vascular access in critically ill neonates should be
      individualized depending on the type and duration of therapy, gestational and
      chronological age, weight and/or size, diagnosis, clinical status, and venous
      system patency. Accordingly, there is an ongoing demand for optimization of
      catheterization. Recently, the use of ultrasound (US)-guided cannulation of the
      subclavian vein (SCV) has been described in children and neonates. This article
      gives an overview of the current use of US for achieving central venous catheter
      placement in the SCV or the brachiocephalic vein (BCV) in neonates. More than
      1,250 catheters have been reported inserted in children and neonates for a
      cumulated success rate of 98.4% and the complication rate is reported to be low.
      The technical aspects of various approaches are discussed, and we offer our
      recommendation of an US-guided technique for SCV and BCV cannulation based on our
      experience in a large NICU setting. Although the cannulation the SCV or BCV does
      not substitute the use of peripherally inserted central catheters or umbilical
      venous central catheters in neonates, it is a feasible route in very small
      children who are in need of a large caliber central venous access.

PMID- 29051891
TI  - Scleroderma Renal Crisis in Mixed Connective Tissue Disease With Full Renal
      Recovery Within 3 Months: A Case Report With Expanding Treatment Modalities to
      Treat Each Clinical Sign as an Independent Entity.
AB  - Mixed connective tissue disease (MCTD) is a rheumatologic overlap syndrome that
      can present with symptoms of systemic lupus erythematous, scleroderma, and
      polymyositis. A severe but rare complication that can occur in MCTD is
      scleroderma renal crisis. With multiple poor prognostic indicators, the renal
      outcome is usually poor. The clinical and histological picture is one of a
      thrombotic microangiopathy. Clinical suspicion has to be high for additional
      thrombotic or autoimmune processes coexisting due to associated morbidity. In
      this article, we report a rare case of scleroderma renal crisis in a patient with
      MCTD who we treated with plasma exchange for clinical suspicion for an underlying
      thrombotic thrombocytopenia and mycophenolate mofetil for MCTD. The patient had
      multiple poor prognostic indicators yet made a full renal recovery in less than 3
      months.

PMID- 29051890
TI  - Considerations for pediatric burn sedation and analgesia.
AB  - Burn patients experience anxiety and pain in the course of their injury,
      treatment, and recovery. Hence, treatment of anxiety and pain is paramount after
      burn injury. Children, in particular, pose challenges in anxiety and pain
      management due to their unique physiologic, psychologic, and anatomic status.
      Burn injuries further complicate pain management and sedation as such injuries
      can have effects on medication response and elimination. Burn injuries further
      complicate pain management and sedation as such injuries can have effects on
      medication response and elimination. The purpose of this review is to describe
      the challenges associated with management of anxiety, pain, and sedation in
      burned children and to describe the different options for treatment of anxiety
      and pain in burned children.

PMID- 29051892
TI  - Autoimmune Pancreatitis Type 2: Case Report.
AB  - A middle-aged man presents with acute pancreatitis of unknown etiology and is
      found to have a presentation consistent with the diagnosis of type 2 autoimmune
      pancreatitis (AIP). AIP is a group of rare heterogeneous diseases that are
      challenging to diagnose. There are 2 types of AIP. Type 1 disease is the more
      common worldwide than type 2 AIP. While type 1 AIP is associated with IgG4
      positive antibodies, type 2 AIP is IgG4 antibody negative. Both types of AIP are
      responsive to corticosteroid treatment. Although type 1 AIP has more
      extrapancreatic manifestations and more commonly relapses, this is a case of a
      patient with type 2 AIP with inflammatory bowel disease and relapsing course.

PMID- 29051893
TI  - Eosinophilic Enteritis: A Delayed Diagnosis.
AB  - Eosinophilic gastrointestinal disorders are a rare and complex group of disorders
      that are characterized by eosinophilic infiltration of the gastrointestinal
      tract. Patients often present with a wide range of signs and symptoms as any
      length or layer of the GI tract can be involved such as mucosal, muscular, or
      serosal. As a part of the workup, patients frequently undergo computed tomography
      scans and multiple endoscopies before the diagnosis is finally made as was true
      in our case of a 59-year-old male patient presenting with 2 months of nausea,
      abdominal pain, and weight loss. He underwent esophagogastroduodenoscopies,
      colonoscopies, video capsule study, and balloon enteroscopy before the diagnosis
      was confirmed histologically. Endoscopic and radiographic findings can be
      variable and are usually unpredictable. The diagnosis is confirmed on
      histopathological examination of biopsies that must show >15-50 eosinophils/high
      power field based on the location in the GI tract. In our patient, erythema,
      scalloping, whitish exudate, and patches of villous blunting were noted in the
      duodenum to proximal ileum endoscopically with >50 eosinophils/high-power field
      confirming the diagnosis of eosinophilic enteritis. This class of diseases is
      often found in patients with a history of allergic disorders suggestive of
      hypersensitivity in the etiology of the disease although our patient had no such
      known history. Elimination diets and steroids are the mainstay of therapy and
      often lead to complete resolution of symptoms as well as endoscopic and
      radiographic findings in up to 90% of patients as was seen in our patient,
      although some patients have a chronic remitting course.

PMID- 29051894
TI  - A Diagnostic Surprise: Primary Hodgkin's Lymphoma of the Lung.
AB  - An 81-year-old male presented to the emergency room with a 3-month history of
      progressive shortness of breath, productive cough with white sputum, and
      generalized weakness with 10-pound weight loss in 2 months. On presentation, the
      patient was afebrile, with blood pressure of 93/55 mm Hg and oxy-hemoglobin
      saturation of 92% on 2 liters of oxygen via nasal cannula. Complete blood count
      with differential was significant for white count of 12 400/mL. Brain natriuretic
      peptide level was 454 ng/mL. Postero-anterior chest radiograph showed multiple
      round opacities in the lung fields. Computed tomography scan of the chest
      confirmed multiple round densities in both the lung fields along with mild
      mediastinal lymphadenopathy. Core needle biopsy was performed.
      Immunohistochemical stains were positive for CD30 and CD15 in a population of
      large atypical cells amid a background of CD3-positive nonneoplastic cells. These
      results were in support of the diagnosis of classical Hodgkin's lymphoma of the
      lung with histological appearance confirming nodular sclerosis type. The patient
      was started on chemotherapy but was readmitted in 20 days for acute respiratory
      distress and suffered cardiac arrest and subsequently died. This case highlights
      the fact that although primary pulmonary Hodgkin's lymphoma of the lung is a rare
      entity, it should be thought of as a differential while evaluating lung masses.
      In these cases, definite diagnosis can only be made by biopsy and histology.
      Early commencement of chemotherapy and regular follow-up with oncology is
      essential.

PMID- 29051895
TI  - Chronic Lymphocytic Leukemia: A Rare Cause of Pathological Fracture of the Femur.
AB  - The incidence rate of chronic lymphocytic leukemia (CLL) in the United States is
      approximately 0.005%; men are at slightly higher risk than women. Bony
      involvement or pathological fracture rarely occurs in CLL, and it may be the
      initial presentation. An 85-year-old woman presented with acute respiratory
      failure secondary to pneumonia. Symptomatology included dyspnea. She was found to
      have pathological fracture of the femur caused by CLL. The diagnosis of CLL had
      been made 6 years previously, but the patient had refused therapy. On admission,
      the patient required endotracheal intubation, mechanical ventilation, and
      admission to the medical intensive care unit. Endotracheal intubation extubation
      was successful after 48 hours. The patient then complained of severe left knee
      pain. Bone radiograph and femoral computed tomography scan revealed acute
      pathological fracture of the left distal femur. There was no history of trauma.
      The fracture was stabilized with extension lock splint. Pathological fracture in
      patients with CLL is associated with hypercalcemia, Richter's transformation, or
      multiple myeloma. This patient exemplifies the fact that pathological fracture
      can be caused by CLL in the absence of hypercalcemia, Richter's transformation,
      or multiple myeloma and can be the initial presentation of CLL.

PMID- 29051896
TI  - Outcomes and Complication Rates After Primary Anterior Cruciate Ligament
      Reconstruction Are Similar in Younger and Older Patients.
AB  - BACKGROUND: Until recently, anterior cruciate ligament (ACL) tears in older
      patients were treated conservatively; however, these patients often experienced
      significant pain and instability. PURPOSE/HYPOTHESIS: The purpose of this study
      was to compare the patient-reported outcomes, patient satisfaction, and failure
      rates of primary ACL reconstruction between a younger (age 20-30 years) and older
      (age 50-75 years) patient cohort. It was hypothesized that patients in the older
      cohort could achieve comparable clinical outcomes and retear rates following ACL
      reconstruction with a bone-tendon-bone autograft or allograft compared with the
      younger patients. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A
      retrospective analysis of prospectively collected data was performed. All
      patients undergoing a primary ACL reconstruction between 2010 and 2014 by a
      single surgeon were collated. Patients were divided into 2 groups based on age at
      the time of surgery: a younger cohort (20-30 years) and an older cohort (50-75
      years). Patients were excluded if they were outside the desired age intervals;
      had revision ACL reconstructions; had a previous intra-articular infection in the
      ipsilateral knee; underwent prior alignment correction procedure, cartilage
      repair, or transplant procedure; had a concurrent posterior cruciate ligament
      tear; received meniscal allograft transplant; or had an intra-articular fracture.
      Subjective outcome scores (Tegner activity scale, Lysholm, International Knee
      Documentation Committee [IKDC], Western Ontario and McMaster Universities
      Osteoarthritis Index [WOMAC], Short Form-12 [SF-12] mental health component
      summary [MCS], and SF-12 physical component summary [PCS]), retear rate, and rate
      of secondary arthrofibrosis surgery were documented at a minimum 2-year follow-up
      and were compared between groups. RESULTS: A total of 85 patients met the
      inclusion criteria for this study: 52 patients (33 males, 19 females) in the
      younger cohort and 33 patients (14 males, 19 females) in the older cohort. No
      significant differences were found in any demographic factor except for age.
      Significant improvement in outcome scores from pre- to postoperative assessments
      was found in both groups. The younger cohort had significantly lower
      postoperative WOMAC scores (P = .025). However, no significant differences were
      found between the younger and older cohorts in postoperative SF-12 PCS (P =
      .487), SF-12 MCS (P = .900), Lysholm score (P = .660), IKDC score (P = .256),
      Tegner activity score (P = .420), or patient satisfaction (P = .060). Within the
      older cohort, increasing age did not correlate with inferior postoperative
      outcome scores. Furthermore, no retears occurred in either group, and the rates
      of arthrofibrosis surgery were comparable (12% older cohort vs 13% younger
      cohort). CONCLUSION: Improved function and satisfaction, comparable to the
      younger age group, were achieved in patients older than 50 years undergoing ACL
      reconstruction. Furthermore, low failure rates can be achieved in both younger
      and older patients undergoing ACL reconstruction.

PMID- 29051897
TI  - The Effect of Regular-Season Rest on Playoff Performance Among Players in the
      National Basketball Association.
AB  - BACKGROUND: There has been speculation that rest during the regular season for
      players in the National Basketball Association (NBA) improves player performance
      in the postseason. PURPOSE: To determine whether there is a correlation between
      the amount of regular-season rest among NBA players and playoff performance and
      injury risk in the same season. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: The Basketball Reference and Pro Sports Transactions archives were
      searched from the 2005 to 2015 seasons. Data were collected on players who missed
      fewer than 5 regular-season games because of rest (group A) and 5 to 9 regular
      season games because of rest (group B) during each season. Inclusion criteria
      consisted of players who played a minimum of 20 minutes per game and made the
      playoffs that season. Players were excluded if they missed >=10 games because of
      rest or suspension or missed >=20 games in a season for any reason. Matched pairs
      were formed between the groups based on the following criteria: position, mean
      age at the start of the season within 2 years, regular-season minutes per game
      within 5 minutes, same playoff seeding, and player efficiency rating (PER) within
      2 points. The following data from the playoffs were collected and compared
      between matched pairs at each position (point guard, shooting guard,
      forward/center): points per game, assists per game, PER, true shooting
      percentage, blocks, steals, and number of playoff games missed because of injury.
      RESULTS: A total of 811 players met the inclusion and exclusion criteria (group
      A: n = 744 players; group B: n = 67 players). Among all eligible players, 27
      matched pairs were formed. Within these matched pairs, players in group B missed
      significantly more regular-season games because of rest than players in group A
      (6.0 games vs 1.3 games, respectively; P < .0001). There were no significant
      differences between the groups at any position in terms of points per game,
      assists per game, PER, true shooting percentage, blocks, steals, or number of
      playoff games missed because of injury. CONCLUSION: Rest during the NBA regular
      season does not improve playoff performance or affect the injury risk during the
      playoffs in the same season.

PMID- 29051898
TI  - Accuracy of the Lever Sign Test in the Diagnosis of Anterior Cruciate Ligament
      Injuries.
AB  - BACKGROUND: The lever sign test is a new physical examination tool to diagnose
      anterior cruciate ligament (ACL) tears. Preliminary results suggest almost 100%
      sensitivity and specificity to diagnose acute and chronic complete ACL tears and
      clinically significant partial tears as compared with magnetic resonance imaging
      (MRI). PURPOSE: To assess the sensitivity and specificity of the lever sign test
      for the diagnosis of acute ACL injuries, as compared to MRI. We also aimed to
      determine the accuracy of the lever sign test compared with 3 other tests
      (anterior drawer, Lachman, and pivot shift) when performed by providers of
      various training levels, and with the patient awake or under anesthesia. STUDY
      DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: We evaluated
      patients with a chief concern of acute (<=4 weeks) knee pain seen between October
      2014 and January 2015, with a thorough history, physical examination, and
      standard radiographs. MRI was the reference standard; patients without an MRI
      evaluation were excluded. The 4 physical examination maneuvers were performed on
      each symptomatic knee during the initial clinic visit (for nonsurgical patients)
      or under anesthesia in the operating room (for surgical patients) by a randomly
      assigned undergraduate student, medical student, orthopaedic resident, or
      orthopaedic fellow. The senior author trained all staff to perform the lever sign
      test. Statistical analyses were performed. RESULTS: Of 102 patients, 54 were
      surgical (28 female, 26 male), and 48 were nonsurgical (16 female, 32 male); the
      mean patient age was 23 years (range, 15-66 years). The overall accuracy of the
      lever sign test was 77% (63% sensitivity, 90% specificity); the accuracy was
      similar between patients under anesthesia and awake (77% vs 76%, respectively).
      There were no significant differences when comparing the sensitivity and
      specificity of the lever sign test with patients under anesthesia and awake
      (sensitivity: under anesthesia, 86%, and awake, 68% [P = .40]; specificity: under
      anesthesia, 85%, and awake, 96% [P = .17]). Furthermore, the accuracy of the
      lever sign test was similar when performed on female versus male patients (75% vs
      79%, respectively) or when performed by undergraduate students and medical
      students compared with orthopaedic residents and fellows (84% vs 88%,
      respectively). CONCLUSION: Our study results challenge the exceptional
      sensitivity and specificity values (both 100%) of the lever sign test, as
      reported by the original author of the test.

PMID- 29051899
TI  - Surgical Treatment of Segond Fractures in Acute Anterior Cruciate Ligament
      Reconstruction.
AB  - BACKGROUND: The Segond fracture is an avulsion-type fracture located on the
      anterolateral aspect of the tibia associated with a ligament recently termed the
      anterolateral ligament. This injury has been described as pathognomonic for an
      anterior cruciate ligament (ACL) tear and is associated with a higher grade pivot
      shift. PURPOSE: To present and report 2-year clinical outcomes of a surgical
      technique for acute ACL reconstruction with fixation of a concomitant Segond
      fracture. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A
      retrospective chart review was performed of patients who underwent acute
      reconstruction for a complete ACL tear with concomitant Segond fracture fixation
      between January 2010 and December 2014; surgery was performed by a single
      surgeon. Patients underwent direct Segond fracture repair by either suture alone,
      suture anchor, or cannulated screw fixation based on the size of the lesion,
      followed by a 2-incision hamstring autograft intra-articular reconstruction. Pre-
      and postoperative KT-1000 arthrometer assessment, Lachman test, and pivot-shift
      test were performed, and patients were administered validated subjective outcome
      surveys. RESULTS: Twelve patients met inclusion criteria for this review. The
      measured pre- and postoperative objective and subjective scores were
      significantly improved in all patients. Side-to-side anterior laxity was
      significantly improved in all patients based on Lachman and KT-1000 arthrometer
      testing. A significant pivot shift demonstrated preoperatively (3+, n = 11 [92%];
      2+, n = 1 [8%]) was corrected after fixation, except in 1 patient (8%), who
      maintained a 1+ pivot shift. Lysholm, Tegner, and International Knee
      Documentation Committee subjective and objective scores were significantly
      improved. At a minimum 2-year follow-up, no patients reported rerupture, and only
      1 patient (8%) underwent a subsequent procedure (a meniscectomy). No major or
      minor complications were reported, and all patients returned to their previous
      activity levels at a mean of 6 months postoperatively. CONCLUSION: Direct repair
      of the Segond fracture and plication of the anterolateral capsule in patients
      with an ACL rupture and a high-grade pivot shift demonstrate good clinical
      outcomes, restoration of rotational stability, and maintenance of knee range of
      motion at 2 years postoperatively, with no major complications.

PMID- 29051900
TI  - Previous Rotator Cuff Repair Is Associated With Inferior Clinical Outcomes After
      Reverse Total Shoulder Arthroplasty.
AB  - BACKGROUND: Although recent evidence suggests that any prior shoulder surgery may
      cause inferior shoulder arthroplasty outcomes, there is no consensus on whether
      previous rotator cuff repair (RCR) is associated with inferior outcomes after
      reverse total shoulder arthroplasty (RTSA). PURPOSE: To retrospectively compare
      outcomes in patients who underwent RTSA with and without previous RCR. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients with prior RCR and
      those without previous shoulder surgery (control) who underwent RTSA for cuff
      tear arthropathy or irreparable cuff tear were retrospectively identified from a
      prospective database. Exclusion criteria included revision arthroplasty,
      fractures, rheumatoid arthritis, dislocations, infection, prior non-RCR
      procedures, less than 12 months of follow-up, and latissimus dorsi tendon
      transfer. The American Shoulder and Elbow Surgeons (ASES) score, ASES Activities
      of Daily Living (ADL) score, visual analog scale (VAS) score for pain, Subjective
      Shoulder Value (SSV), and range of motion (ROM) were compared between groups.
      RESULTS: Patients with previous RCR (n = 83 shoulders) were younger (mean +/- SD,
      67 +/- 10 vs 72 +/- 8 years; P < .001) and more likely to be male (46% vs 32%, P
      = .033) than controls (n = 189 shoulders). No differences were found in follow-up
      duration (25 +/- 13 vs 26 +/- 13 months, P = .734), body mass index, or any
      preoperative outcome variable or ROM measure. At final follow-up, patients with
      previous RCR had significantly lower ASES (76.5 [95% CI, 71.2-81.7] vs 85.0 [82.6
      87.5], P = .015), lower SSV (76 [72-81] vs 86 [83-88], P < .001), worse pain (2.0
      [1.4-2.6] vs 0.9 [0.6-1.1], P < .001), and less improvement in the ASES, ASES
      ADL, VAS, SSV, and forward elevation measures than controls. Multivariable linear
      regression analysis demonstrated that previous RCR was significantly associated
      with lower postoperative ASES score (B = -9.5, P < .001), lower ASES improvement
      (B = -7.9, P = .012), worse postoperative pain (B = 0.9, P = .001), worse
      improvement in pain (B = -1.0, P = .011), lower postoperative SSV (B = -9.2, P <
      .001), lower SSV improvement (B = -11.1, P = .003), and lower forward elevation
      ROM improvement (B = -12.7, P = .008). CONCLUSION: Patients with previous RCR
      attempts may experience fewer short-term gains in functional and subjective
      outcome scores after RTSA compared with patients with no history of shoulder
      surgery who undergo RTSA. However, the differences between groups were small and
      below the minimal clinically important differences for the outcome measures
      analyzed.

PMID- 29051901
TI  - Fresh Osteochondral Allograft Transplantation for Spontaneous Osteonecrosis of
      the Knee: A Case Series.
AB  - BACKGROUND: Spontaneous osteonecrosis of the knee (SONK) is a clinical entity
      identified by acute knee pain usually associated with joint effusion, with
      radiographic findings of a radiolucent defect on the weightbearing area of the
      femoral condyle. Conservative treatment is initially undertaken; however,
      surgical procedures are often necessary. Historically, surgical options have
      included core decompression, cartilage repair, high tibial osteotomy, or joint
      arthroplasty. Few studies in the literature have reported the use of fresh
      osteochondral allograft (OCA) for the treatment of SONK lesions. HYPOTHESIS: OCA
      transplantation is an effective treatment for SONK lesions on the medial femoral
      condyle. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A case series
      was analyzed of 7 patients treated with OCA for large SONK lesions of the medial
      femoral condyle with a minimum 4-year follow-up. All patients experienced failure
      of at least 6 months of conservative treatment and declined arthroplasty as the
      form of definitive treatment for medial femoral condyle lesion. All patients
      underwent OCA of the medial femoral condyle. Mean lesion size was 4.6 cm2 (range,
      3.24-6.25 cm2), with a mean condylar width of 41.7 mm (range, 35.4-48.6 mm),
      resulting in a median proportion (lesion size/condylar width) of 56.8% (range,
      32.7%-62.6%). The median surface allograft area was 5.1 cm2 (range, 3.2-6.3 cm2).
      RESULTS: The median follow-up was 7.1 years (range, 4.5-14.1 years). No patient
      had additional surgery following OCA transplant; the allograft failure rate was
      0%. Subjective outcome scores from the International Knee Documentation
      Committee, Knee injury and Osteoarthritis Outcome Score, and modified Merle
      d'Aubigne-Postel scale improved from preoperative assessment to the latest follow
      up. All patients were extremely satisfied with the results of the OCA transplant.
      CONCLUSION: Fresh OCA transplantation demonstrated excellent efficacy,
      durability, and satisfaction in this group of patients with isolated stage 2 and
      3 SONK lesions who had experienced failure of conservative treatment. Fresh
      osteochondral allografts are an attractive method for surgical management of
      selected patients with spontaneous osteonecrosis of the knee.

PMID- 29051902
TI  - Trends in Surgical Practices for Lateral Epicondylitis Among Newly Trained
      Orthopaedic Surgeons.
AB  - BACKGROUND: Much controversy exists regarding the optimal surgical intervention
      for lateral epicondylitis because of a multitude of options available and the
      lack of comparative studies. Knowledge of the current practice trends would help
      guide the design of comparative studies needed to determine which surgical
      technique results in the best outcome. PURPOSE: To review the latest practice
      trends for the surgical treatment of lateral epicondylitis among newly trained
      surgeons in the United States utilizing the American Board of Orthopaedic Surgery
      (ABOS) database. STUDY DESIGN: Cross-sectional study; Level of evidence, 3.
      METHODS: The ABOS database was utilized to identify surgical cases for lateral
      epicondylitis submitted by Part II board certification examination candidates
      from 2004 through 2013. Inclusion criteria were predetermined using a combination
      of International Classification of Diseases, Ninth Revision (ICD-9) and Current
      Procedural Terminology (CPT) codes. Cases were organized by open and arthroscopic
      treatment groups and by fellowship training and were analyzed to determine
      differences in surgical techniques, complication rates, and concomitant
      procedures. RESULTS: In total, 1150 surgeons submitted 2106 surgical cases for
      the treatment of lateral epicondylitis. The number of surgical cases for lateral
      epicondylitis performed per 10,000 submitted cases significantly decreased from
      26.7 in 2004 to 21.1 in 2013 (P = .002). Among all cases, 92.2% were open and
      7.8% were arthroscopic, with no change in the incidence of arthroscopic surgeries
      over the study period. Shoulder and elbow (18.1%) and sports medicine (11.4%)
      surgeons were more likely to perform surgery arthroscopically compared with hand
      surgeons (6.1%) (P < .001). There was no difference in overall self-reported
      complication rates between open (4.4%) and arthroscopic (5.5%) procedures (P =
      .666). Percutaneous tenotomy, debridement only, and debridement with tendon
      repair comprised 6.4%, 46.3%, and 47.3% of open treatment, respectively. Sports
      medicine, hand, and shoulder and elbow surgeons were more likely to repair the
      tendon after debridement compared with other surgeons, who were more likely to
      perform debridement alone (P < .001). Hand surgeons were most likely to perform
      concomitant procedures, of which the majority were neuroplasties. CONCLUSION:
      Although comparative studies are ultimately necessary for determining the optimal
      surgical technique, researchers should be mindful of the differences in practices
      according to training and the extent to which concomitant procedures are being
      performed, as both these factors may confound any future results.

PMID- 29051903
TI  - The Anterolateral Complex of the Knee.
AB  - BACKGROUND: Significant controversy exists regarding the anterolateral structures
      of the knee. PURPOSE: To determine the layer-by-layer anatomic structure of the
      anterolateral complex of the knee. STUDY DESIGN: Descriptive laboratory study.
      METHODS: Twenty fresh-frozen cadaveric knees (age range, 38-56 years) underwent a
      layer-by-layer dissection to systematically expose and identify the various
      structures of the anterolateral complex. Quantitative measurements were
      performed, and each layer was documented with high-resolution digital imaging.
      RESULTS: The anterolateral complex of the knee consisted of different distinct
      layers, with the superficial and deep iliotibial band (ITB) representing layer 1.
      The superficial ITB had a distinct connection to the distal femoral metaphysis
      and femoral condyle (Kaplan fibers), and the deep layers of the ITB were
      identified originating at the level of the Kaplan fibers proximally. This
      functional unit, consisting of the superficial and deep ITB, was reinforced by
      the capsulo-osseous layer of the ITB, which was continuous with the fascia of the
      lateral gastrocnemius and biceps femoris muscles. These 3 components of the ITB
      became confluent distally, and the insertion spanned from the Gerdy tubercle
      anteriorly to the lateral tibia posteriorly on a small tubercle (lateral tibial
      tuberosity). Layer 3 consisted of the anterolateral capsule, in which 35% (7/20)
      of specimens had a discreet mid-third capsular ligament. CONCLUSION: The
      anterolateral complex consists of the superficial and deep ITB, the capsulo
      osseous layer of the ITB, and the anterolateral capsule. The anterolateral
      complex is defined by the part of the ITB between the Kaplan fibers proximally
      and its tibial insertion, which forms a functional unit. A discrete anterolateral
      ligament was not observed; however, the anterolateral ligament described in
      recent studies likely refers to the capsulo-osseous layer or the mid-third
      capsular ligament. CLINICAL RELEVANCE: The anterolateral knee structures form a
      complex functional unit. Surgeons should use caution when attempting to restore
      this intricate structure with extra-articular procedures designed to re-create a
      single discreet ligament.

PMID- 29051904
TI  - Distal Semimembranosus Tendon Avulsions: Acute Surgical Repair in a Professional
      Rugby Player.

PMID- 29051905
TI  - Evaluation of the Trends, Concomitant Procedures, and Complications With Open and
      Arthroscopic Rotator Cuff Repairs in the Medicare Population.
AB  - BACKGROUND: Medicare insures the largest population of patients at risk for
      rotator cuff tears in the United States. PURPOSE: To evaluate the trends in
      incidence, concomitant procedures, and complications with open and arthroscopic
      rotator cuff repairs in Medicare patients. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: All Medicare patients who had undergone open or
      arthroscopic rotator cuff repair from 2005 through 2011 were identified with a
      claims database. Annual incidence, concomitant procedures, and postoperative
      complications were compared between these 2 groups. RESULTS: In total, 372,109
      rotator cuff repairs were analyzed. The incidence of open repairs decreased (from
      6.0 to 4.3 per 10,000 patients, P < .001) while the incidence of arthroscopic
      repairs increased (from 4.5 to 7.8 per 10,000 patients, P < .001) during the
      study period. Patients in the arthroscopic group were more likely to have
      undergone concomitant subacromial decompression than those in the open group (87%
      vs 35%, P < .001), and the annual incidence of concomitant biceps tenodesis
      increased for both groups (from 3.8% to 11% for open and 2.2% to 16% for
      arthroscopic, P < .001). While postoperative complications were infrequent,
      patients in the open group were more likely to be diagnosed with infection within
      6 months (0.86% vs 0.37%, P < .001) but no more likely to undergo operative
      debridement (0.43% vs 0.26%, P = .08). Additionally, patients in the open group
      were more likely to undergo intervention for shoulder stiffness within 1 year
      (1.4% vs 1.1%, P = .01). CONCLUSION: In the Medicare population, arthroscopic
      rotator cuff repairs have increased in incidence and now represent the majority
      of rotator cuff repair surgery. Among concomitant procedures, subacromial
      decompression was most commonly performed despite evidence suggesting a lack of
      efficacy. Infections and stiffness were rare complications that were slightly but
      significantly more frequent in open rotator cuff repairs.

PMID- 29051906
TI  - Intra-articular Physeal Fractures of the Distal Femur: A Frequently Missed
      Diagnosis in Adolescent Athletes.
AB  - BACKGROUND: Intra-articular physeal fractures of the distal femur are an uncommon
      injury pattern, with only a few small case series reported in the literature.
      PURPOSE: To pool patients from 3 high-volume pediatric centers to better
      understand this injury pattern, to determine outcomes of surgical treatment, and
      to assess risk factors for complications. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: A multicenter retrospective review of all patients
      presenting with an intra-articular physeal fracture between 2006 and 2016 was
      performed. Patient demographic and injury data, surgical data, and postoperative
      outcomes were documented. Radiographs were evaluated for fracture classification
      (Salter-Harris), location, and displacement. Differences between patients with
      and without complications were compared by use of analysis of variance or chi
      square tests. RESULTS: A total of 49 patients, with a mean age of 13.5 years
      (range, 7-17 years), met the inclusion criteria. The majority of fractures were
      Salter-Harris type III fractures (84%) involving the medial femoral condyle
      (88%). Football was responsible for 50% of the injuries. The initial diagnosis
      was missed in 39% of cases, and advanced imaging showed greater mean displacement
      (6 mm) compared with radiographs (3 mm). All patients underwent surgery and
      returned to sport with "good to excellent" results after 2 years. Complications
      were more common in patients with wide-open growth plates, patients with
      fractures involving the lateral femoral condyle, and patients who were casted (P
      < .05). CONCLUSION: Clinicians evaluating skeletally immature athletes
      (particularly football players) with acute knee injuries should maintain a high
      index of suspicion for an intra-articular physeal fracture. These fractures are
      frequently missed, and advanced imaging may be required to establish the
      diagnosis. Leg-length discrepancies and angular deformities are not uncommon, and
      patients should be monitored closely. Surgical outcomes are good when fractures
      are identified, with high rates of return to sport.

PMID- 29051907
TI  - Online BCI Typing using Language Model Classifiers by ALS Patients in their
      Homes.
AB  - The P300 speller is a common brain-computer interface system that can provide a
      means of communication for patients with amyotrophic lateral sclerosis (ALS).
      Recent studies have shown that incorporating language information in signal
      classification can improve system performance, but they have largely been tested
      on healthy volunteers in a laboratory setting. The goal of this study was to
      demonstrate the functionality of the P300 speller system with language models
      when used by ALS patients in their homes. Six ALS patients with functional
      ratings ranging from two to 28 participated in this study. All subjects had
      improved offline performance when using a language model and five subjects were
      able to type at least six characters per minute with over 84% accuracy in online
      sessions. The results of this study indicate that the improvements in performance
      using language models in the P300 speller translate into the ALS population,
      which could help to make it a viable assistive device.

PMID- 29051908
TI  - Lesion-symptom mapping in the study of spoken language understanding.
AB  - Lesion-symptom mapping studies aim to make inferences about the functional
      neuroanatomy of spoken language understanding by investigating relationships
      between damage to different brain regions and the various speech perception and
      comprehension deficits that result. Voxel-based lesion-symptom mapping (VLSM),
      voxel-based morphometry (VBM), and studies focused on specific cortical regions
      of interest or fiber pathways have all yielded insights regarding the
      localization of different components of spoken language processing. Major
      challenges include the fact that brain damage rarely impacts just a single brain
      region or just a single processing component, and that neuroplasticity and
      recovery can complicate the interpretation of lesion-deficit correlations. Future
      studies involving large patient cohorts derived from multi-center projects, and
      multivariate approaches to quantifying patterns of brain damage and patterns of
      linguistic deficits, will continue to yield new insights into the neural basis of
      spoken language understanding.

PMID- 29051909
TI  - Performance Monitoring in Children Following Traumatic Brain Injury Compared to
      Typically Developing Children.
AB  - Children with traumatic brain injury are reported to have deficits in performance
      monitoring, but the mechanisms underlying these deficits are not well understood.
      Four performance monitoring hypotheses were explored by comparing how 28 children
      with traumatic brain injury and 28 typically developing controls (matched by age
      and sex) performed on the stop-signal task. Control children slowed significantly
      more following incorrect than correct stop-signal trials, fitting the error
      monitoring hypothesis. In contrast, the traumatic brain injury group showed no
      performance monitoring difference with trial types, but significant group
      differences did not emerge, suggesting that children with traumatic brain injury
      may not perform the same way as controls.

PMID- 29051910
TI  - CEDNIK: Phenotypic and Molecular Characterization of an Additional Patient and
      Review of the Literature.
AB  - Synaptosomal-associated protein 29 (SNAP29) is a t-SNARE protein that is
      implicated in intracellular vesicle fusion. Mutations in the SNAP29 gene have
      been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma
      syndrome (CEDNIK). In patients with 22q11.2 deletion syndrome, mutations in
      SNAP29 on the nondeleted chromosome are linked to similar ichthyotic and
      neurological phenotypes. Here, the authors report a patient with cerebral
      dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome who presented with
      global developmental delay, polymicrogyria, dysgenesis of the corpus callosum,
      optic nerve dysplasia, gaze apraxia, and dysmorphic features. He has developed
      ichthyosis and palmoplantar keratoderma as he has grown. Exome sequencing
      identified a homozygous nonsense mutation in SNAP29 gene designated as c.85C>T
      (p.Arg29X). The authors compare the findings in the proband with previously
      reported cases. The previously unreported mutation in this patient and his
      phenotype add to the characterization of cerebral dysgenesis, neuropathy,
      ichthyosis, and keratoderma syndrome and the accumulating scientific evidence
      that implicates synaptic protein dysfunction in various neuroectodermal
      conditions.

PMID- 29051911
TI  - Is the Effect of Parental Education on Offspring Biased or Moderated by Genotype?
AB  - Parental education is the strongest measured predictor of offspring education,
      and thus many scholars see the parent-child correlation in educational attainment
      as an important measure of social mobility. But if social changes or policy
      interventions are going to have dynastic effects, we need to know what accounts
      for this intergenerational association, that is, whether it is primarily
      environmental or genetic in origin. Thus, to understand whether the estimated
      social influence of parental education on offspring education is biased owing to
      genetic inheritance (or moderated by it), we exploit the findings from a recent
      large genome-wide association study of educational attainment to construct a
      genetic score designed to predict educational attainment. Using data from two
      independent samples, we find that our genetic score significantly predicts years
      of schooling in both between-family and within-family analyses. We report three
      findings that should be of interest to scholars in the stratification and
      education fields. First, raw parent-child correlations in education may reflect
      one-sixth genetic transmission and five-sixths social inheritance. Second,
      conditional on a child's genetic score, a parental genetic score has no
      statistically significant relationship to the child's educational attainment.
      Third, the effects of offspring genotype do not seem to be moderated by measured
      sociodemographic variables at the parental level (but parent-child genetic
      interaction effects are significant). These results are consistent with the
      existence of two separate systems of ascription: genetic inheritance (a random
      lottery within families) and social inheritance (across-family ascription). We
      caution, however, that at the presently attainable levels of explanatory power,
      these results are preliminary and may change when better-powered genetic risk
      scores are developed.

PMID- 29051912
TI  - Evaluating Diabetes Care for Patients With Serious Mental Illness Using the
      Chronic Care Model: A Pilot Study.
AB  - People with serious mental illness (SMI) have a higher incidence of type 2
      diabetes mellitus (T2DM) and shorter life span due to medical health problems.
      The chronic care model (CCM) has been used to improve care of patients with T2DM.
      One clinical organization that provided primary care to patients with SMI had
      excellent diabetes outcomes but did not have information on how they achieved
      those outcomes. Thus, we conducted a pilot study chart review for 30 patients
      with T2DM and SMI to determine how well the clinic's system aligned with the
      overall CCM components and which components correlated with diabetes control. We
      also evaluated use of the CCM using the Assessment of Chronic Illness Care
      provider survey. Results showed that the clinic had an overall basic
      implementation level of the CCM, which allows opportunity for improvement. Two
      elements of the CCM were correlated with hemoglobin A1C and both were in an
      unexpected direction: self-management support in the variable of percentage of
      visits that included patient-specific goal-setting (rs = .52; P = .004) and
      delivery system design in the variable of number of nurse practitioner visits per
      study period (rs = .43; P = .02). These findings suggest that the clinic may have
      made more concentrated efforts to manage diabetes for patients who were not in
      good diabetes control. Providers noted the influence of SMI and social service
      organization support on these patients' clinical outcomes. The findings will be
      reexamined after a fuller implementation of the CCM to further improve management
      in this population.

PMID- 29051914
TI  - A 17-Year-Old Girl With Weight Loss and Anemia.

PMID- 29051913
TI  - Patients With Dementia Are Easy Victims to Predators.
AB  - Patients with dementia, especially Alzheimer's disease and particularly those in
      early stages, are susceptible to become victims of predators: Their agnosia (see
      Case 1) prevents them from detecting and accurately interpreting subtle signals
      that otherwise would have alerted them that they are about to fall for a scam.
      Furthermore, their judgment is impaired very early in the disease process, often
      before other symptoms manifest themselves and usually before a diagnosis is made.
      Patients with early stages of dementia are therefore prime targets for
      unscrupulous predators, and it behooves caregivers and health care professionals
      to ensure the integrity of these patients. In this case study, we discuss how a
      man with mild Alzheimer's disease was about to fall for a scam were it not for
      his vigilant wife. We discuss what went wrong in the patient/caregiver
      interaction and how the catastrophic ending could have been avoided or averted.

PMID- 29051915
TI  - Pediatric Testicular Microlithiasis: To Refer or Not to Refer?

PMID- 29051916
TI  - A New Dyslexia Reading Method and Visual Correction Position Method.
AB  - Pediatricians and educators may interact daily with several dyslexic patients or
      students. One dyslexic author accidently developed a personal, effective,
      corrective reading method. Its effectiveness was evaluated in 3 schools. One
      school utilized 8 demonstration special education students. Over 3 months, one
      student grew one third year, 3 grew 1 year, and 4 grew 2 years. In another
      school, 6 sixth-, seventh-, and eighth-grade classroom teachers followed 45
      treated dyslexic students. They all excelled and progressed beyond their
      classroom peers in 4 months. Using cyclovergence upper gaze, dyslexic reading
      problems disappeared at one of the Positional Reading Arc positions of 30 degrees
      , 60 degrees , 90 degrees , 120 degrees , or 150 degrees  for 10 dyslexics.
      Positional Reading Arc on 112 students of the second through eighth grades showed
      words read per minute, reading errors, and comprehension improved. Dyslexia was
      visually corrected by use of a new reading method and Positional Reading Arc
      positions.

PMID- 29051917
TI  - Perceptions of the Food and Drug Administration as a Tobacco Regulator.
AB  - OBJECTIVES: The U. S. Food and Drug Administration (FDA) now has regulatory
      authority over all tobacco products. Little is known about public awareness and
      perceptions of FDA in their new role as a tobacco regulator. This research
      utilizes focus groups to examine perceptions of FDA as a tobacco regulator so
      that FDA can better communicate with the public about this role. METHODS: We
      conducted 6 focus groups in 2014 among a diverse sample of smokers and non
      smokers. Participants were asked if they had heard of FDA, what they knew about
      FDA, if they associated FDA with tobacco, and their thoughts about this FDA role.
      RESULTS: A total of 41 individuals participated. Although nearly all participants
      had heard of FDA, most were not aware of FDA's regulatory authority over tobacco
      products, did not associate the role of FDA with tobacco, and some drew
      comparisons between FDA's work in tobacco and their work regulating food and
      drugs. CONCLUSION: Data suggest that although public awareness of FDA regulatory
      authority over tobacco is low, with proper public education, the public may find
      FDA to be a trustworthy source of tobacco regulation.

PMID- 29051918
TI  - Effects of ensemble and summary displays on interpretations of geospatial
      uncertainty data.
AB  - Ensemble and summary displays are two widely used methods to represent visual
      spatial uncertainty; however, there is disagreement about which is the most
      effective technique to communicate uncertainty to the general public.
      Visualization scientists create ensemble displays by plotting multiple data
      points on the same Cartesian coordinate plane. Despite their use in scientific
      practice, it is more common in public presentations to use visualizations of
      summary displays, which scientists create by plotting statistical parameters of
      the ensemble members. While prior work has demonstrated that viewers make
      different decisions when viewing summary and ensemble displays, it is unclear
      what components of the displays lead to diverging judgments. This study aims to
      compare the salience of visual features - or visual elements that attract bottom
      up attention - as one possible source of diverging judgments made with ensemble
      and summary displays in the context of hurricane track forecasts. We report that
      salient visual features of both ensemble and summary displays influence
      participant judgment. Specifically, we find that salient features of summary
      displays of geospatial uncertainty can be misunderstood as displaying size
      information. Further, salient features of ensemble displays evoke judgments that
      are indicative of accurate interpretations of the underlying probability
      distribution of the ensemble data. However, when participants use ensemble
      displays to make point-based judgments, they may overweight individual ensemble
      members in their decision-making process. We propose that ensemble displays are a
      promising alternative to summary displays in a geospatial context but that
      decisions about visualization methods should be informed by the viewer's task.

PMID- 29051919
TI  - Protein crystallization: Eluding the bottleneck of X-ray crystallography.
AB  - To date, X-ray crystallography remains the gold standard for the determination of
      macromolecular structure and protein substrate interactions. However, the
      unpredictability of obtaining a protein crystal remains the limiting factor and
      continues to be the bottleneck in determining protein structures. A vast amount
      of research has been conducted in order to circumvent this issue with limited
      success. No single method has proven to guarantee the crystallization of all
      proteins. However, techniques using antibody fragments, lipids, carrier proteins,
      and even mutagenesis of crystal contacts have been implemented to increase the
      odds of obtaining a crystal with adequate diffraction. In addition, we review a
      new technique using the scaffolding ability of PDZ domains to facilitate
      nucleation and crystal lattice formation. Although in its infancy, such
      technology may be a valuable asset and another method in the crystallography
      toolbox to further the chances of crystallizing problematic proteins.

PMID- 29051920
TI  - Personalized management of asthma exacerbations: lessons from genetic studies.
AB  - INTRODUCTION: The genetics of severe asthma and asthma exacerbations are distinct
      from milder forms of asthma. Gene-environmental interactions contribute to the
      complexity and heterogeneity of severe asthma and asthma exacerbations, and
      pharmacogenomic studies have also identified genes that affect susceptibility to
      asthma exacerbations. AREAS COVERED: Studies on the genetics, gene-environment
      interactions, and pharmacogenomics of asthma exacerbations are reviewed. Multiple
      individual genetic variants have been identified to be associated with asthma
      exacerbations but each genetic polymorphism explains only a fraction of the
      disease and by itself is not able to translate into clinical practice. Research
      is shifting from candidate gene studies and genome wide association studies
      towards more integrative approaches to translate genetic findings into clinical
      diagnostic and therapeutic tools. EXPERT COMMENTARY: Integrative approaches
      combining polygenic or genomic data with multi-omics technologies have the
      potential to discover new biologic mechanisms and biomarkers for severe asthma
      and asthma exacerbations. Greater understanding of genomics and underlying
      biologic pathways will also lead to improved prevention and treatment, lowering
      costs, morbidity, and mortality. The utilization of genomic testing and
      personalized medicine may revolutionize asthma management, in particular for
      patients with severe, refractory asthma.

PMID- 29051921
TI  - Effectiveness of Schroth exercises during bracing in adolescent idiopathic
      scoliosis: results from a preliminary study-SOSORT Award 2017 Winner.
AB  - BACKGROUND: Bracing has been shown to decrease significantly the progression of
      high-risk curves to the threshold for surgery in patients with adolescent
      idiopathic scoliosis (AIS), but the treatment failure rate remains high. There is
      evidence to suggest that Schroth scoliosis-specific exercises can slow
      progression in mild scoliosis. The aim of this study was to evaluate the efficacy
      of Schroth exercises in AIS patients with high-risk curves during bracing.
      METHODS: A prospective, historical cohort-matched study was carried out. Patients
      diagnosed with AIS who fulfilled the Scoliosis Research Society (SRS) criteria
      for bracing were recruited to receive Schroth exercises during bracing. An
      outpatient-based Schroth program was given. Data for these patients were compared
      with a 1:1 matched historical control group who were treated with bracing alone.
      The assessor and statistician were blinded. Radiographic progression, truncal
      shift, and SRS-22r scores were compared between cases and controls. RESULTS:
      Twenty-four patients (5 males and 19 females, mean age 12.3 +/- 1.4 years) were
      included in the exercise group, and 24 patients (mean age 11.8 +/- 1.1 years)
      were matched in the control group. The mean follow-up period for the exercise
      group was 18.1 +/- 6.2 months. In the exercise group, spinal deformity improved
      in 17% of patients (Cobb angle improvement of >= 6 degrees ), worsened in 21%
      (Cobb angle increases of >= 6 degrees ), and remained stable in 62%. In the
      control group, 4% improved, 50% worsened, and 46% remained stable. In the
      subgroup analysis, 31% of patients who were compliant (13 cases) improved, 69%
      remained static, and none had worsened, while in the non-compliant group (11
      cases), none had improved, 46% worsened, and 46% remained stable. Analysis of the
      secondary outcomes showed improvement of the truncal shift, angle of trunk
      rotation, the SRS function domain, and total scores in favor of the exercise
      group. CONCLUSION: This is the first study to investigate the effects of Schroth
      exercises on AIS patients during bracing. Our findings from this preliminary
      study showed that Schroth exercise during bracing was superior to bracing alone
      in improving Cobb angles, trunk rotation, and QOL scores. Furthermore, those who
      were compliant with the exercise program had a higher rate of Cobb angle
      improvement. The results of this study form the basis for a randomized controlled
      trial to evaluate the effect of Schroth exercises during bracing in AIS. TRIAL
      REGISTRATION: HKUCTR-2226. Registered 22 June 2017 (retrospectively registered).

PMID- 29051922
TI  - Hidden heritability due to heterogeneity across seven populations.
AB  - Meta-analyses of genome-wide association studies (GWAS), which dominate genetic
      discovery are based on data from diverse historical time periods and populations.
      Genetic scores derived from GWAS explain only a fraction of the heritability
      estimates obtained from whole-genome studies on single populations, known as the
      'hidden heritability' puzzle. Using seven sampling populations (N=35,062), we
      test whether hidden heritability is attributed to heterogeneity across sampling
      populations and time, showing that estimates are substantially smaller from
      across compared to within populations. We show that the hidden heritability
      varies substantially: from zero (height), to 20% for BMI, 37% for education, 40%
      for age at first birth and up to 75% for number of children. Simulations
      demonstrate that our results more likely reflect heterogeneity in phenotypic
      measurement or gene-environment interaction than genetic heterogeneity. These
      findings have substantial implications for genetic discovery, suggesting that
      large homogenous datasets are required for behavioural phenotypes and that gene
      environment interaction may be a central challenge for genetic discovery.

PMID- 29051923
TI  - Testing a Multidimensional Acculturation Model on Latinos who Completed Substance
      Abuse Treatment.
AB  - Disparities in substance abuse treatment (SAT) utilization and completion suggest
      that traditional substance abuse models may fall short of addressing the complex
      needs of Latinos, increasing the odds of relapsing. The need for substance use
      models that integrate multiple acculturation domains in relation to substance
      abuse is warranted. The goal of the present study is twofold: a) test a
      multidimensional acculturation model on Latinos who completed SAT; and b) examine
      the association between the proposed multidimensional acculturation and days
      consuming alcohol and illicit drugs in the past six months. A total of 131
      participants (Mage=36.15, SD +/- 10.5, 86.3% males, 48.1% non-U.S. born with a
      mean length of stay of 19 years in the U.S. (SD +/- 13.71) were interviewed upon
      completion of SAT. Results from the SEM indicated adequate model fit to the
      population under study, supporting the use of a multidimensional acculturation
      approach for this population. Subsequent results from the structured regression
      analysis suggest that multidimensional acculturation is negatively associated
      with days using alcohol in the past 6 months. The implications of these findings
      are discussed.

PMID- 29051924
TI  - Pre-vaccine circulating group a rotavirus strains in under 5 years children with
      acute diarrhea during 1999-2013 in Cameroon.
AB  - The aim of this review was to assess all the studies on rotavirus G and P
      characterization during the pre-vaccine period (1999-2013) in Cameroon to have a
      better basis for post-vaccine introduction evaluations. A retrospective study was
      done through a comprehensive review of published (PubMed, Google Scholar) and
      accessible unpublished data on rotavirus G and P genotypes circulating in five
      regions of Cameroon. Descriptive data were expressed as frequencies tables and
      proportions. A total of 1844 rotavirus positive cases were analyzed. In all, 1534
      strains were characterized for the P (VP4) specificity. Six different VP4
      genotypes were observed, including P [4], P [6], P [8], P [9], P [10] and P [14].
      The most predominant P genotypes were P [8] at 42.6%, and P [6] at 37.9%. Mixed
      infections were observed at 5.3%, whereas 4.1% of the strains were P non
      typeable. A total of 1518 rotavirus strains were characterized for the G (VP7)
      specificity. VP7 genotypes G1, G2, G3, G4, G5, G6, G8, G9, G10 and G12 were
      observed. G1 (35.3%), G3 (19.5%), G2 (14.9%) and G12 (10.1%) were the predominant
      G genotypes while G5 and G10 were least prevalent at 0.06% each. Approximately
      5.1% of all strains were G non-typeable whereas 5.3% were mixed G genotypes. A
      total of 1472 strains were characterized for both G and P genes, from which 38
      different G-P combinations were observed. Overall, G1P [8] (22%) was identified
      as the predominant rotavirus strain circulating in Cameroon followed by G3P [6]
      (15%). In conclusion, we observed that the genotypes identified in Cameroon
      during 1999-2013 were partially covered by the two WHO recommended rotavirus
      vaccines. This review provides comprehensive up-to-date information on rotavirus
      strain surveillance in Cameroon during the pre-vaccination era.

PMID- 29051925
TI  - Opportunities and Design Considerations for Peer Support in a Hospital Setting.
AB  - Although research has demonstrated improved outcomes for outpatients who receive
      peer support-such as through online health communities, support groups, and
      mentoring systems-hospitalized patients have few mechanisms to receive such
      valuable support. To explore the opportunities for a hospital-based peer support
      system, we administered a survey to 146 pediatric patients and caregivers, and
      conducted semi-structured interviews with twelve patients and three caregivers in
      a children's hospital. Our analysis revealed that hospitalized individuals need
      peer support for five key purposes: (1) to ask about medical details-such as
      procedures, treatments, and medications; (2) to learn about healthcare providers;
      (3) to report and prevent medical errors; (4) to exchange emotional support; and
      (5) to manage their time in the hospital. In this paper, we examine these themes
      and describe potential barriers to using a hospital-based peer support system. We
      then discuss the unique opportunities and challenges that the hospital
      environment presents when designing for peer support in this setting.

PMID- 29051926
TI  - Examining Multi-Level Correlates of Suicide by Merging NVDRS and ACS Data.
AB  - This paper describes a novel database and an associated suicide event prediction
      model that surmount longstanding barriers in suicide risk factor research. The
      database comingles person-level records from the National Violent Death Reporting
      System (NVDRS) and the American Community Survey (ACS) to establish a case
      control study sample that includes all identified suicide cases, while faithfully
      reflecting general population sociodemographics, in sixteen USA states during the
      years 2005-2011. It supports a statistical model of individual suicide risk that
      accommodates person-level factors and the moderation of these factors by their
      community rates. Named the United States Multi-Level Suicide Data Set (US-MSDS),
      the database was developed outside the RDC laboratory using publicly available
      ACS microdata, and reconstructed inside the laboratory using restricted access
      ACS microdata. Analyses of the latter version yielded findings that largely
      amplified but also extended those obtained from analyses of the former. This
      experience shows that the analytic precision achievable using restricted access
      ACS data can play an important role in conducting social research, although it
      also indicates that publicly available ACS data have considerable value in
      conducting preliminary analyses and preparing to use an RDC laboratory. The
      database development strategy may interest scientists investigating
      sociodemographic risk factors for other types of low-frequency mortality.

PMID- 29051927
TI  - Heteromultimetallic catalysis for sustainable organic syntheses.
AB  - Fully complementary bimetallic catalysis has been identified as an increasingly
      powerful tool for molecular transformations, which was largely inspired by early
      examples of sequential catalytic transformations. Thus, energy-efficient one-pot
      reactions involving different metal catalysts orchestrated in concert constitute
      an attractive alternative to multi-step protocols, with major recent progress
      through the elegant ligand design in heterobimetallic catalysis as well as
      sustainable photo-induced C-H transformations, among others. This review provides
      a critical assessment of the state of the art in heterobimetallic catalysis for
      sustainable organic syntheses (SOS), highlighting key advances and representative
      examples until summer 2017.

PMID- 29051928
TI  - Accessing 2-substituted piperidine iminosugars by organometallic
      addition/intramolecular reductive amination: aldehyde vs. nitrone route.
AB  - A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is
      disclosed. The procedure involved Grignard addition either to a carbohydrate
      derived aldehyde or to a nitrone derived thereof, and took advantage of an
      efficient ring-closure reductive amination strategy in the final cyclization
      step. An opposite diastereofacial preference was demonstrated in the nucleophilic
      attack to the two electrophiles, which would finally produce the same piperidine
      diastereoisomer as the major product. However, use of a suitable Lewis acid in
      the Grignard addition to the nitrone allowed reversing the selectivity, giving
      access to 2-substituted piperidines with the opposite configuration at C-2.

PMID- 29051929
TI  - Fully chip-embedded automation of a multi-step lab-on-a-chip process using a
      modularized timer circuit.
AB  - For highly-integrated microfluidic systems, an actuation system is necessary to
      control the flow; however, the bulk of actuation devices including pumps or
      valves has impeded the broad application of integrated microfluidic systems.
      Here, we suggest a microfluidic process control method based on built-in
      microfluidic circuits. The circuit is composed of a fluidic timer circuit and a
      pneumatic logic circuit. The fluidic timer circuit is a serial connection of
      modularized timer units, which sequentially pass high pressure to the pneumatic
      logic circuit. The pneumatic logic circuit is a NOR gate array designed to
      control the liquid-controlling process. By using the timer circuit as a built-in
      signal generator, multi-step processes could be done totally inside the microchip
      without any external controller. The timer circuit uses only two valves per unit,
      and the number of process steps can be extended without limitation by adding
      timer units. As a demonstration, an automation chip has been designed for a six
      step droplet treatment, which entails 1) loading, 2) separation, 3) reagent
      injection, 4) incubation, 5) clearing and 6) unloading. Each process was
      successfully performed for a pre-defined step-time without any external control
      device.

PMID- 29051930
TI  - A two-photon excitable and ratiometric fluorogenic nitric oxide photoreleaser and
      its biological applications.
AB  - We report for the first time the development of a two-photon excitable NO
      photoreleaser, CNNO, for ratiometric imaging and tracking of NO release in live
      cells. CNNO exhibits the merits of spatiotemporal control in both the site
      specific NO release in the selected cell culture region and the controllable
      vasodilation of mouse aorta ex vivo.

PMID- 29051931
TI  - Fullerene hexa-adduct scaffolding for the construction of giant molecules.
AB  - Hexa-substituted fullerenes are unique scaffolds for the fast construction of
      globular dendrimers. Efficient synthetic methodologies based on the post
      functionalization of pre-constructed fullerene hexa-adduct derivatives have been
      reported in recent years and dendrimers difficult or even impossible to prepare
      by classical fullerene chemistry are now easily accessible. Fullerodendrimers for
      various applications have been thus prepared. Examples include liquid crystalline
      materials, non-viral gene delivery systems and bioactive glycoclusters. On the
      other hand, fullerene hexa-adduct building blocks have been used for the ultra
      fast synthesis of giant dendrimers. Indeed, the resulting dendrimers of first
      generation are already surrounded by 120 peripheral functional groups. This
      strategy has been used to prepare giant glycoclusters with anti-viral activity
      and multivalent glycosidase inhibitors.

PMID- 29051932
TI  - Activation of CO2 by supported Cu clusters.
AB  - Catalytic reduction of carbon dioxide to useful chemicals is a potent way to
      mitigate this greenhouse gas, but the challenge lies in finding active reduction
      catalysts. Using density functional theory we studied CO2 activation over TiO2
      supported Cu clusters of size 1-4 atoms. The linear to bent transformation of CO2
      is necessary for activation, and we found that all the clusters stabilized bent
      CO2, along with a significant gain of electrons on the CO2 (indicative of
      activation). On all the TiO2 supported Cu clusters, the interfacial sites were
      found to stabilize the bent CO2 adsorption, where the active site of adsorption
      on Cu dimer, trimer and tetramer was on the Cu atom farthest away from the TiO2
      surface. Particularly, the Cu dimer stabilized bent CO2 very strongly, although
      this species was found to be unstable on the surface. A synthesis technique that
      could stabilize the Cu dimer could therefore lead to a very active catalyst.
      Furthermore we found (using vibrational and charge analysis) that the active
      sites for the CO2 activation predominantly had 0 and +1 oxidation states; the
      oxidation state of Cu is known to directly affect CO2 reduction activity. Our
      study shows TiO2-supported small Cu clusters can be active catalysts for CO2
      reduction and also provides further motivation for theoretical and experimental
      studies of metal clusters.

PMID- 29051934
TI  - Forced intrusion of water and aqueous solutions in microporous materials: from
      fundamental thermodynamics to energy storage devices.
AB  - We review the high pressure forced intrusion studies of water in hydrophobic
      microporous materials such as zeolites and MOFs, a field of research that has
      emerged some 15 years ago and is now very active. Many of these studies are aimed
      at investigating the possibility of using these systems as energy storage
      devices. A series of all-silica zeolites (zeosil) frameworks were found suitable
      for reversible energy storage because of their stability with respect to
      hydrolysis after several water intrusion-extrusion cycles. Several microporous
      hydrophobic zeolite imidazolate frameworks (ZIFs) also happen to be quite stable
      and resistant towards hydrolysis and thus seem very promising for energy storage
      applications. Replacing pure water by electrolyte aqueous solutions enables to
      increase the stored energy by a factor close to 3, on account of the high
      pressure shift of the intrusion transition. In addition to the fact that aqueous
      solutions and microporous silica materials are environmental friendly, these
      systems are thus becoming increasingly interesting for the design of new energy
      storage devices. This review also addresses the theoretical approaches and
      molecular simulations performed in order to better understand the experimental
      behavior of nano-confined water. Molecular simulation studies showed that water
      condensation takes place through a genuine first-order phase transition, provided
      that the interconnected pores structure is 3-dimensional and sufficiently open.
      In an extreme confinement situations such as in ferrierite zeosil, condensation
      seem to take place through a continuous supercritical crossing from a diluted to
      a dense fluid, on account of the fact that the first-order transition line is
      shifted to higher pressure, and the confined water critical point is
      correlatively shifted to lower temperature. These molecular simulation studies
      suggest that the most important features of the intrusion/extrusion process can
      be understood in terms of equilibrium thermodynamics considerations.

PMID- 29051935
TI  - Synthesis and reduction of large sized graphene oxide sheets.
AB  - Graphene oxide (GO) can be considered as one of the most visible outcomes of
      graphene research in terms of large scale production and commercialization
      prospects. Although GO can be easily prepared by oxidation-exfoliation of
      graphite in agitated solutions, the size of these sheets is generally limited due
      to fragmentation along fault lines during chemical oxidation and exfoliation in
      agitated solutions. In this account, we discuss recent strategies which have been
      developed for the preparation of large sized graphene oxide (LGO) sheets with
      lateral sizes >10 MUm, using chemically expanded graphite as the starting
      material. LGO has a much lower density of defects than GO prepared using the
      conventional Hummers' method and can be readily transformed into graphene by
      chemical reduction. In addition, the unique advantages of using LGO sheets as a
      performance enhancer are discussed. Finally, this review also discusses recent
      advances in the chemical and electrochemical reduction of graphene oxide.

PMID- 29051933
TI  - Peptide-based fibrin-targeting probes for thrombus imaging.
AB  - The development of new methods to image the onset and progression of thrombosis
      is an unmet need. Non-invasive molecular imaging techniques targeting specific
      key structures involved in the formation of thrombosis have demonstrated the
      ability to detect thrombus in different disease state models and in patients. Due
      to its high concentration in the thrombus and its essential role in thrombus
      formation, the detection of fibrin is an attractive strategy for identification
      of thrombosis. Herein we provide an overview of recent and selected fibrin
      targeted probes for molecular imaging of thrombosis by magnetic resonance imaging
      (MRI), positron emission tomography (PET), single photon emission computed
      tomography (SPECT), and optical techniques. Emphasis is placed on work that our
      lab has explored over the last 15 years that has resulted in the progression of
      the fibrin-binding PET probe [64Cu]FBP8 from preclinical studies into human
      trials.

PMID- 29051936
TI  - NiO-nanoflakes grafted graphene: an excellent photocatalyst and a novel
      nanomaterial for achieving complete pathogen control.
AB  - The increased levels of industrial pollutants in water and of drug-resistant
      pathogens more generally are a serious threat to human and aquatic life. Herein,
      we present the solar-light-induced dye removal and bactericidal properties of
      nickel oxide (NiO) and graphene nanoplatelet (GNP) nanocomposites. The conducting
      nature of GNPs is the key factor that accounts for the enhanced photocatalytic
      and antibacterial activity. Remarkably, the graphene/NiO nanocomposite shows
      outstanding photocatalytic activity (99% degradation) as compared to NiO (34%)
      alone, which makes it a potential candidate for the depollution of dye
      contaminated water. In addition, the optimized amount of GNPs in the graphene/NiO
      nanocomposite renders it an exceptional antibacterial material, producing 100%
      growth inhibition of pathogenic microorganisms (both Gram-positive and Gram
      negative bacteria). Therefore, the graphene/NiO nanocomposite can be an
      innovative material to achieve complete pathogen control, alongside being an
      economic solution for water treatment.

PMID- 29051937
TI  - Molecular dynamics simulations of beta2-microglobulin interaction with
      hydrophobic surfaces.
AB  - Hydrophobic surfaces are known to adsorb and unfold proteins, a process that has
      been studied only for a few proteins. Here we address the interaction of beta2
      microglobulin, a paradigmatic protein for the study of amyloidogenesis, with
      hydrophobic surfaces. A system with 27 copies of the protein surrounded by a
      model cubic hydrophobic box is studied by implicit solvent molecular dynamics
      simulations. Most proteins adsorb on the walls of the box without major
      distortions in local geometry, whereas free molecules maintain proper structures
      and fluctuations as observed in explicit solvent molecular dynamics simulations.
      The major conclusions from the simulations are as follows: (i) the adopted
      implicit solvent model is adequate to describe protein dynamics and
      thermodynamics; (ii) adsorption occurs readily and is irreversible on the
      simulated timescale; (iii) the regions most involved in molecular encounters and
      stable interactions with the walls are the same as those that are important in
      protein-protein and protein-nanoparticle interactions; (iv) unfolding following
      adsorption occurs at regions found to be flexible by both experiments and
      simulations; (v) thermodynamic analysis suggests a very large contribution from
      van der Waals interactions, whereas unfavorable electrostatic interactions are
      not found to contribute much to adsorption energy. Surfaces with different
      degrees of hydrophobicity may occur in vivo. Our simulations show that adsorption
      is a fast and irreversible process which is accompanied by partial unfolding. The
      results and the thermodynamic analysis presented here are consistent with and
      rationalize previous experimental work.

PMID- 29051938
TI  - Mechanistic exploration of the copper(i) phosphide synthesis in phosphonium-based
      and phosphorus-free ionic liquids.
AB  - The mechanism of the synthesis of copper(i) phosphide (Cu3-xP) in the ionic
      liquid (IL) trihexyl(tetradecyl)phosphonium chloride ([P66614][Cl]) was
      investigated. The phosphide formation is promoted by a transformation of red
      phosphorus (Pred) into mobile P4 molecules and a surface activation of copper
      caused by the IL including the Bronsted acidic impurity. The surface activation
      is important to obtain a quantitative product yield. Moreover, we demonstrate
      that single-phase Cu3-xP can also be synthesized in the nitrogen-based IL
      tetrabutylammonium chloride ([N4444][Cl]). Further substitution of the anion of
      the IL using tetrabutylammonium bromide ([N4444][Br]) or the complete replacement
      of the IL by a deep eutectic solvent consisting of adipic acid and betaine do not
      lead to single-phase Cu3-xP. Therefore, the nature of the anions present in the
      IL also seems to be relevant for the convenient phosphidization reaction.

PMID- 29051939
TI  - Mechanistic investigation on N -> Calpha -> O relay via non-Brook rearrangement:
      reaction conditions promote synthesis of furo[3,2-c]pyridinones.
AB  - A comprehensive density functional theory investigation was employed to disclose
      the effect of reaction conditions on the mechanism and effective anion relay
      sequence of a NaH promoted non-Brook rearrangement of benzaldehyde and 1
      cinnamoylcyclopropanecarboxamides. Two main mechanisms were explored under four
      different reaction conditions: Na+-assisted and nH2O-Na+, 2H2O-DMSO-Na+, and Na+
      DMSO co-assisted, and the difference relies on the reaction sequence between the
      concerted ring-opening and recyclization and electrophilic addition. Being
      different from previous reports, a cooperative participation of water, solvent
      DMSO and counterion Na+ is revealed in the preferential mechanism. The preferred
      scenario undergoes five major steps: deprotonation, aza-Michael addition,
      electrophilic addition, NaOH elimination and a concerted ring-opening and
      recyclization step. The rate-determining step is the concerted ring-opening and
      recyclization process with an energy barrier of 30.2 kcal mol-1. We found that
      the effective anion relay of a non-Brook rearrangement order is N -> Calpha -> O
      rather than the previously proposed aza-oxy-carbanion. Meanwhile, a mixed type of
      ARC chemistry through a novel non-Brook rearrangement was disclosed. Moreover,
      the non-covalent interactions between substrate and reactant extensively affect
      the anion relay process by hydrogen-bonding (O-HO and C-HO) and electrostatic
      (Na+O) interactions. Thus, our results provide insightful clues to the mechanism
      of the reaction condition catalyzed non-Brook rearrangement reaction.

PMID- 29051940
TI  - Non-linear sweep voltammetry of adsorbed species: theory and a method to
      determine formal potentials.
AB  - Recent literature revealed the hitherto unexploited opportunities offered by
      unconventional cyclic voltammetry with non-triangular potential sweeps. We here
      investigate the implications of such techniques for the equilibrium voltammetry
      of surface-bound analytes and expose rather counter-intuitive effects: if only
      slightly different potential waveforms are applied, distinct and characteristic
      features arise in the voltammogram that can be readily exploited for quantitative
      analysis. Our work comprises a theoretical analysis and suggests initially a
      simple method to determine formal potentials.

PMID- 29051941
TI  - Fortified beeswax oleogels: effect of beta-carotene on the gel structure and
      oxidative stability.
AB  - This study was aimed at evaluating the physical conformation and oxidative
      stability of beeswax oleogels when fortified by the incorporation of beta
      carotene (complex-beeswax oleogels). Rheological evaluation showed the presence
      of a strengthened structural conformation in the oleogels with beta-carotene in
      comparison with that in oleogels without beta-carotene; this was verified by the
      increase in rheological parameters. Small angle X-ray scattering data show that
      the lamellar crystal structure of the oleogels with beta-carotene exhibits
      similar d-spacings and lower radius of gyration (Rg) values for all
      concentrations due to the stronger oleogel network. X-ray diffraction
      measurements provide useful information on the crystal polymorphism type and
      arrangement of the internal lamellar phases of the crystals. Oil binding capacity
      is also affected by the incorporation of beta-carotene into the oleogel and
      proven to be higher for the complex-beeswax oleogels, which enhances the ability
      of the oleogels to retain an oil phase within their crystalline network. The
      oxidative profiles of the complex-beeswax oleogels were studied during storage,
      and beeswax at the concentrations of 4, 6, and 8% revealed higher oxidative
      stability than that at the concentration of 2%. In this study, the possibility of
      tailoring the properties of oleogels is demonstrated considering the foreseen
      applications of oleogels in food products, such as in texturizers, as well their
      capacity to deliver bioactives and thus add value to food products.

PMID- 29051943
TI  - Thermal and electronic transport characteristics of highly stretchable graphene
      kirigami.
AB  - For centuries, cutting and folding papers with special patterns have been used to
      build beautiful, flexible and complex three-dimensional structures. Inspired by
      the old idea of kirigami (paper cutting), and the outstanding properties of
      graphene, recently graphene kirigami structures were fabricated to enhance the
      stretchability of graphene. However, the possibility of further tuning the
      electronic and thermal transport along the 2D kirigami structures has remained
      original to investigate. We therefore performed extensive atomistic simulations
      to explore the electronic, heat and load transfer along various graphene kirigami
      structures. The mechanical response and thermal transport were explored using
      classical molecular dynamics simulations. We then used a real-space Kubo
      Greenwood formalism to investigate the charge transport characteristics in
      graphene kirigami. Our results reveal that graphene kirigami structures present
      highly anisotropic thermal and electrical transport. Interestingly, we show the
      possibility of tuning the thermal conductivity of graphene by four orders of
      magnitude. Moreover, we discuss the engineering of kirigami patterns to further
      enhance their stretchability by more than 10 times as compared with pristine
      graphene. Our study not only provides a general understanding concerning the
      engineering of electronic, thermal and mechanical response of graphene, but more
      importantly can also be useful to guide future studies with respect to the
      synthesis of other 2D material kirigami structures, to reach highly flexible and
      stretchable nanostructures with finely tunable electronic and thermal properties.

PMID- 29051942
TI  - Methods for monitoring and measurement of protein translation in time and space.
AB  - Regulation of protein translation constitutes a crucial step in control of gene
      expression. In comparison to transcriptional regulation, however, translational
      control has remained a significantly under-studied layer of gene expression. This
      trend is now beginning to shift thanks to recent advances in next-generation
      sequencing, proteomics, and microscopy based methodologies which allow accurate
      monitoring of protein translation rates, from single target messenger RNA
      molecules to genome-wide scale studies. In this review, we summarize these recent
      advances, and discuss how they are enabling researchers to study translational
      regulation in a wide variety of in vitro and in vivo biological systems, with
      unprecedented depth and spatiotemporal resolution.

PMID- 29051944
TI  - Confined methane-water interfacial layers and thickness measurements using in
      situ Raman spectroscopy.
AB  - Gas-liquid interfaces broadly impact our planet, yet confined interfaces behave
      differently than unconfined ones. We report the role of tangential fluid motion
      in confined methane-water interfaces. The interfaces are created using
      microfluidics and investigated by in situ 1D, 2D and 3D Raman spectroscopy. The
      apparent CH4 and H2O concentrations are reported for Reynolds numbers (Re),
      ranging from 0.17 to 8.55. Remarkably, the interfaces are comprised of distinct
      layers of thicknesses varying from 23 to 57 MUm. We found that rarefaction,
      mixture, thin film, and shockwave layers together form the interfaces. The
      results indicate that the mixture layer thickness (delta) increases with Re
      (delta ? Re), and traditional transport theory for unconfined interfaces does not
      explain the confined interfaces. A comparison of our results with thin film
      theory of air-water interfaces (from mass transfer experiments in capillary
      microfluidics) supports that the hydrophobicity of CH4 could decrease the
      strength of water-water interactions, resulting in larger interfacial
      thicknesses. Our findings help explain molecular transport in confined gas-liquid
      interfaces, which are common in a broad range of societal applications.

PMID- 29051945
TI  - Cancer classification with a network of chemical oscillators.
AB  - We discuss chemical information processing considering dataset classifiers formed
      with a network of interacting droplets. Our arguments are based on computer
      simulations of droplets in which a photosensitive variant of the Belousov
      Zhabotinsky (BZ) reaction proceeds. By applying optical control we can adjust the
      time evolution of individual droplets and prepare the network to perform a
      specific computational task. We demonstrate that chemical classifiers made of
      droplets can be designed in computer simulations based on evolutionary
      algorithms. The mutual information between the dataset and the observed time
      evolution of droplets in the network is taken as the fitness function in the
      optimization process. We show that a classifier of the Wisconsin Breast Cancer
      Dataset made of a relatively small number of droplets can distinguish between
      malignant and benign forms of cancer with an accuracy exceeding 97%. The
      reliability of the optimized chemical classifiers of this dataset as a function
      of optimization time, number of droplets involved in data processing and the
      method of extracting the output information is discussed.

PMID- 29051946
TI  - Cluster transformation of [Cu3(MU3-H)(MU3-BH4)((PPh2)2NH)3](BF4) to [Cu3(MU3
      H)(MU2,MU1-S2CH)((PPh2)2NH)3](BF4) via reaction with CS2. X-ray structural
      characterisation and reactivity of cationic clusters explored by multistage mass
      spectrometry and computational studies.
AB  - The copper nanocluster [Cu3(MU3-H)(MU3-BH4)LPh3](BF4), 1a.BF4 (LPh = (PPh2)2NH =
      dppa), can potentially react with substrates at either the coordinated hydride or
      borohydride sites. Reaction of 1a.BF4 with CS2 has given rise to [Cu3(MU3
      H)(MU2,MU1-S2CH)LPh3](BF4), (2a.BF4), which was structurally characterised using
      electrospray ionisation (ESI) with high-resolution mass spectrometry (HRMS), X
      ray crystallography, NMR, IR and UV-Vis spectroscopy. The copper(i) atoms adopt a
      planar trinuclear Cu3 geometry coordinated on the bottom face by a MU3-hydride,
      on the top face by a MU2,MU1-dithioformate and surrounded by three bridging LPh
      ligands. Reaction of 1a.BF4 with elemental sulfur gives the known cluster
      [Cu4(LPh-H + 2S)3](BF4), (3.BF4), which was structurally characterised via X-ray
      crystallography. ESI-MS of 2a.BF4 produces [Cu3(H)(S2CH)LPh3]+ and its gas-phase
      ion chemistry was examined under multistage mass spectrometry conditions using
      collision-induced dissociation (CID). The primary product, [Cu3(H)(S2CH)LPh2]+,
      formed via ligand loss, undergoes further fragmentation via loss of
      thioformaldehyde to give [Cu3(S)LPh2]+. DFT calculations exploring rearrangement
      and fragmentation of the model system [Cu3(H)(S2CH)LMe2]+ (LMe = (PMe2)2NH =
      dmpa) provide a feasible mechanism. Thus, coupling of the coordinated hydride
      with the dithioformate ligands gives [Cu3(S2CH2)LMe2]+, which then undergoes CH2S
      extrusion via C-S bond cleavage to give [Cu3(S)LMe2]+.

PMID- 29051947
TI  - Pre-steady-state kinetic analysis of damage recognition by human single-strand
      selective monofunctional uracil-DNA glycosylase SMUG1.
AB  - In all organisms, DNA glycosylases initiate base excision repair pathways
      resulting in removal of aberrant bases from DNA. Human SMUG1 belongs to the
      superfamily of uracil-DNA glycosylases catalyzing the hydrolysis of the N
      glycosidic bond of uridine and uridine lesions bearing oxidized groups at C5: 5
      hydroxymethyluridine (5hmU), 5-formyluridine (5fU), and 5-hydroxyuridine (5hoU).
      An apurinic/apyrimidinic (AP) site formed as the product of an N-glycosylase
      reaction is tightly bound to hSMUG1, thus inhibiting the downstream action of AP
      endonuclease APE1. The steady-state kinetic parameters (kcat and KM; obtained
      from the literature) correspond to the enzyme turnover process limited by the
      release of hSMUG1 from the complex with the AP-site. In the present study, our
      objective was to carry out a stopped-flow fluorescence analysis of the
      interaction of hSMUG1 with a DNA substrate containing a dU:dG base pair to follow
      the pre-steady-state kinetics of conformational changes in both molecules. A
      comparison of kinetic data obtained by means of Trp and 2-aminopurine
      fluorescence and Forster resonance energy transfer (FRET) detection allowed us to
      elucidate the stages of specific and nonspecific DNA binding, to propose the
      mechanism of damaged base recognition by hSMUG1, and to determine the true rate
      of the catalytic step. Our results shed light on the kinetic mechanism underlying
      the initiation of base excision repair by hSMUG1 using the "wedge" strategy for
      DNA lesion search.

PMID- 29051948
TI  - CuOTf-mediated intramolecular diborene hydroarylation.
AB  - Upon complexation to CuOTf, a PMe3-stabilized bis(9-anthryl) diborene slowly
      undergoes an intramolecular hydroarylation reaction at room temperature.
      Subsequent triflation of the B-H bond with CuOTf, followed by a PMe3 transfer,
      finally yields a cyclic sp2-sp3 boryl-substituted boronium triflate salt.

PMID- 29051949
TI  - Correction: Bismuth oxyiodide coupled with bismuth nanodots for enhanced
      photocatalytic bisphenol A degradation: synergistic effects and mechanistic
      insight.
AB  - Correction for 'Bismuth oxyiodide coupled with bismuth nanodots for enhanced
      photocatalytic bisphenol A degradation: synergistic effects and mechanistic
      insight' by Shunqin Luo et al., Nanoscale, 2017, DOI: 10.1039/c7nr05320g.

PMID- 29051950
TI  - Self-assembly of peptide amphiphiles for drug delivery: the role of peptide
      primary and secondary structures.
AB  - Peptide amphiphiles (PAs), functionalized with alkyl chains, are capable of self
      assembling into various nanostructures. Recently, PAs have been considered as
      ideal drug carriers due to their good biocompatibility, specific biological
      functions, and hypotoxicity to normal cells and tissues. Meanwhile, the
      nanocarriers formed by PAs are able to achieve controlled drug release and
      enhanced cell uptake in response to the stimulus of the physiological environment
      or specific biological factors in the location of the lesion. However, the
      underlying detailed drug delivery mechanism, especially from the aspect of
      primary and secondary structures of PAs, has not been systematically summarized
      or discussed. Focusing on the relationship between the primary and secondary
      structures of PAs and stimuli-responsive drug delivery applications, this review
      highlights the recent advances, challenges, and opportunities of PA-based
      functional drug nanocarriers, and their potential pharmaceutical applications are
      discussed.

PMID- 29051951
TI  - Straightforward synthesis of Man9, the relevant epitope of the high-mannose
      oligosaccharide.
AB  - The high-mannose oligosaccharide (or its corresponding Man9 epitope) is the most
      abundant structure present in pathogen envelope glycoproteins. These glycans play
      a key role in the pathogenesis of several pathogens and also in the communication
      with the immune system. Understanding the mechanism of action of these glycans
      requires the access to pure and chemically well-defined structures in reasonable
      amounts. The synthesis of these complex branched oligosaccharides is not trivial
      and few syntheses are reported in the literature with several synthetic and
      purification steps and low overall yields. In this work, we described a very
      efficient synthetic alternative to access this relevant Man9 epitope in a very
      straightforward manner.

PMID- 29051952
TI  - Insights into human intrinsically disordered proteins from their gene expression
      profile.
AB  - Expression level provides important clues about gene function. Previously,
      various efforts have been undertaken to profile human genes according to their
      expression level. Intrinsically disordered proteins (IDPs) do not adopt any rigid
      conformation under physiological conditions, however, are considered as an
      important functional class in all domains of life. Based on a human tissue
      averaged gene expression level, previous studies showed that IDPs are expressed
      at a lower level than ordered globular proteins. Here, we examined the gene
      expression pattern of human ordered and disordered proteins in 32 normal tissues.
      We noticed that in most of the tissues, ordered and disordered proteins are
      expressed at a similar level. Moreover, in a number of tissues IDPs were found to
      be expressed at a higher level than ordered proteins. Rigorous statistical
      analyses suggested that the lower tissue-averaged gene expression level of IDPs
      (reported earlier) may be the consequence of their biased gene expression in some
      specific tissues and higher protein length. When we considered the gene repertory
      of each tissue we noticed that a number of human tissues (brain, testes, etc.)
      selectively express a higher fraction of disordered proteins, which help them to
      maintain higher protein connectivity by forming disordered binding motifs and to
      sustain their functional specificities. Our results demonstrated that the
      disordered proteins are indispensable in these tissues for their functional
      advantages.

PMID- 29051953
TI  - Effects of multifunctional cross-linkers on rheology and adhesion of soft
      nanostructured materials.
AB  - We investigate the nanostructure, the rheology and the adhesion of soft
      supramolecular materials elaborated by blending monofunctional and
      multifunctional poly(isobutene) (PIB) chains. Monofunctional PIB chains (PIBUT)
      are linear and unentangled polymer chains (Mn ~ 3 kg mol-1) functionalized in the
      middle by a bis-urea interacting moiety, able to self-associate by four hydrogen
      bonds. Covalent coupling of monofunctional PIB allows us to synthesize longer
      chains bearing two or three interacting moieties. These chains are then added to
      monofunctional PIB to prepare blends containing up to 10% of multifunctional PIB
      (M-PIBUT). The influence of M-PIBUT on the supramolecular nanostructure, which
      results from the self-assembly of stickers, is studied by Atomic Force Microscopy
      and Small Angle X-ray Scattering at room temperature. Multifunctional and
      monofunctional chains are shown to interact with each other to form bundles of
      rod-like aggregates. The consequences of these interactions on the rheology of
      the blends were studied by shear tests in the linear and non linear regimes,
      below and above the order-disorder transition temperature. A pronounced
      strengthening effect of M-PIBUT is observed at room temperature: the
      supramolecular blends become more elastic and are more resistant to creep with
      increasing concentration of M-PIBUT. The effects of M-PIBUT on the nanostructure
      and the rheology suggest that M-PIBUT, which can link with more than one
      supramolecular aggregate, plays the role of a physical cross-linker. The impact
      of these supramolecular cross-linkers on the adhesion of the blends is studied by
      probe-tack tests and discussed by analyzing the in situ deformation through the
      debonding images.

PMID- 29051954
TI  - The development of a Panax notoginseng medicinal liquor processing technology
      using the response surface method and a study of its antioxidant activity and its
      effects on mouse melanoma B16 cells.
AB  - Panax notoginseng medicinal liquor (PML) has a long history of use in the
      function of blood circulation. However, the processing of PML is currently
      dependent on experience, which results in low efficiency and unstable quality of
      PML. A variety of substances of P. notoginseng have a strong ability to scavenge
      free radicals and antioxidant activity, but the antioxidant activity of PML has
      not been formally researched. The aim of the present study was to optimize the
      processing technology of PML and to verify the anti-oxidation and anti-deposition
      of melanin functions of PML. Based on the Box-Behnken design of response surface
      method, the PML processing parameters were established as follows: the ratio of
      liquid to solid 32 : 1, 53% of alcohol, and soaking time of 35 d. With elevating
      concentration of PML extract, the reducing force and scavenging rates of DPPH,
      superoxide anion, hydroxyl radical and ABTS+ were increased, and the inhibition
      rate of tyrosinase activity and the melanin synthesis ability were increased in
      mice melanoma B16 cells. Thus, the optimal processing technology not only
      shortened the processing time but also decreased the material costs. PML may be
      developed as food or beauty products for the functions of anti-oxidation and anti
      deposition of melanin.

PMID- 29051960
TI  - Comment on "Relating side chain organization of PNIPAm with its conformation in
      aqueous methanol" by D. Mukherji, M. Wagner, M. D. Watson, S. Winzen, T. E. de
      Oliveira, C. M. Marques and K. Kremer, Soft Matter, 2016, 12, 7995.
AB  - In a recent article, Kremer and co-workers have combined NMR measurements and
      very long, all-atom MD simulations to strengthen their original claim that PNIPAM
      cononsolvency in water-methanol solutions is driven by the ability of MeOH
      molecules to bridge different monomers far away along the polymeric chain. In
      this comment, the results presented by Kremer and co-workers are reviewed,
      analyzed, and questioned regarding their ability to provide support to the
      bridging mechanism. Here, some pieces of evidence are provided to show that: (1)
      the solvent-excluded volume effect plays always a fundamental role in polymer
      collapse; (2) PNIPAM cononsolvency is caused by the geometric-energetic
      frustration experienced by the polymer when it can interact with both water and
      methanol molecules at the same time.

PMID- 29051961
TI  - Hierarchically interconnected nitrogen-doped carbon nanosheets for an efficient
      hydrogen evolution reaction.
AB  - Exploring low-cost and efficient electrocatalysts based on earth-abundant
      elements for the hydrogen evolution reaction (HER) is of great importance for the
      development of clean and renewable energy. In this work, we report a facile self
      foaming strategy for synthesis of hierarchically interconnected nitrogen-doped
      carbon nanosheets (NCNS). The doping N species within the 3D interconnected
      carbon network affords rich active sites for the HER and facilitates fast charge
      transfer. As a result, the NCNS exhibit excellent catalytic activity with an
      onset potential of -65 mV, and a Tafel slope of 81 mV dec-1 with robust stability
      over 10 h in acidic media. Further analyses suggest that the graphitic N species
      in the NCNS contribute to their catalytic activity. Such a high catalytic
      performance makes the NCNS a promising metal-free HER electrocatalyst for
      practical hydrogen production.

PMID- 29051962
TI  - Structural disorder, filament growth and self-poisoning in short rods confined
      onto a flat wall.
AB  - Confocal microscopy was used to directly observe the structural coarsening of the
      first layer of short colloidal rods sedimented onto a flat wall. Based on an
      image analysis algorithm we devised, quantitative information on the location,
      orientation and length of each particle can be extracted with high precision. At
      high density the system undergoes structural arrest, and becomes trapped in a
      disordered state of randomly arranged filaments that are composed of side-by-side
      aligned rods. The frustration of structural order is signalled by a new peak that
      emerges in the radial distribution function. Configuration analysis shows that
      the peak is primarily due to pairs of particles that are arranged in a "T" shape,
      a configuration that is compatible with neither crystallization nor filament
      growth. Our results point to a self-poisoning mechanism for the frustration of
      structural order, and highlight the importance of particle shape in controlling
      colloidal assembly thus materials properties.

PMID- 29051963
TI  - Applications of particulate oxygen-generating substances (POGS) in the
      bioartificial pancreas.
AB  - Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the
      destruction of beta cells within the pancreas. A promising treatment strategy for
      T1D is the replacement of the lost beta cell mass through implantation of immune
      isolated microencapsulated islets referred to as the bioartificial pancreas. The
      goal of this approach is to restore blood glucose regulation and prevent the long
      term comorbidities of T1D without the need for immunosuppressants. A major
      requirement in the quest to achieve this goal is to address the oxygen needs of
      islet cells. Islets are highly metabolically active and require a significant
      amount of oxygen for normal function. During the process of isolation,
      microencapsulation, and processing prior to transplantation, the islets' oxygen
      supply is disrupted, and a large amount of islet cells are therefore lost due to
      extended hypoxia, thus creating a major barrier to clinical success with this
      treatment. In this work, we have investigated the oxygen generating compounds,
      sodium percarbonate (SPO) and calcium peroxide (CPO) as potential supplemental
      oxygen sources for islets during isolation and encapsulation before and
      immediately after transplantation. First, SPO particles were used as an oxygen
      source for islets during isolation. Secondly, silicone films containing SPO were
      used to provide supplemental oxygen to islets for up to 4 days in culture.
      Finally, CPO was used as an oxygen source for encapsulated cells by co
      encapsulating CPO particles with islets in permselective alginate microspheres.
      These studies provide an important proof of concept for the utilization of these
      oxygen generating materials to prevent beta cell death caused by hypoxia.

PMID- 29051965
TI  - Abstracts from the 37th Congress of the Societe Internationale d'Urologie, Centro
      de Congressos de Lisboa, October 19-22, 2017.

PMID- 29051964
TI  - Identification of quality improvement areas in pediatric MRI from analysis of
      patient safety reports.
AB  - BACKGROUND: Analysis of safety reports has been utilized to guide practice
      improvement efforts in adult magnetic resonance imaging (MRI). Data specific to
      pediatric MRI could help target areas of improvement in this population.
      OBJECTIVE: To estimate the incidence of safety reports in pediatric MRI and to
      determine associated risk factors. MATERIALS AND METHODS: In a retrospective
      HIPAA-compliant, institutional review board-approved study, a single-institution
      Radiology Information System was queried to identify MRI studies performed in
      pediatric patients (0-18 years old) from 1/1/2010 to 12/31/2015. The safety
      report database was queried for events matching the same demographic and dates.
      Data on patient age, gender, location (inpatient, outpatient, emergency room
      [ER]), and the use of sedation/general anesthesia were recorded. Safety reports
      were grouped into categories based on the cause and their severity. Descriptive
      statistics were used to summarize continuous variables. Chi-square analyses were
      performed for univariate determination of statistical significance of variables
      associated with safety report rates. A multivariate logistic regression was used
      to control for possible confounding effects. RESULTS: A total of 16,749 pediatric
      MRI studies and 88 safety reports were analyzed, yielding a rate of 0.52%. There
      were significant differences in the rate of safety reports between patients
      younger than 6 years (0.89%) and those older (0.41%) (P<0.01), sedated (0.8%) and
      awake children (0.45%) (P<0.01), and inpatients (1.1%) and outpatients (0.4%)
      (P<0.01). The use of sedation/general anesthesia is an independent risk factor
      for a safety report (P=0.02). The most common causes for safety reports were
      service coordination (34%), drug reactions (19%), and diagnostic test and
      ordering errors (11%). CONCLUSION: The overall rate of safety reports in
      pediatric MRI is 0.52%. Interventions should focus on vulnerable populations,
      such as younger patients, those requiring sedation, and those in need of acute
      medical attention.

PMID- 29051967
TI  - Clinical efficacy of transforaminal epidural injection for management of zoster
      associated pain: a retrospective analysis.
AB  - OBJECTIVES: Transforaminal epidural injection (TFEI) has superior accessibility
      to the dorsal root ganglion, which is an essential location of pain signaling in
      herpes zoster. However, the effectiveness of TFEI for herpes zoster patients has
      not previously been studied. We retrospectively analyzed the efficacy of TFEI for
      pain control and prevention of PHN in patients with acute and subacute herpes
      zoster. METHODS: Medical records of 137 patients who underwent TFEI for zoster
      associated pain (ZAP) were reviewed. The participants were divided into two
      groups: acute TFEI group (TFEI within 30 days after zoster) and subacute TEEI
      group (TFEI between 30 and 90 days). The efficacy of TFEI was assessed by a
      numerical rating scale (NRS), doses of medications, and time to relief of ZAP.
      Incidence of PHN at 1 week to 6 months after TFEI was evaluated. RESULTS: Time to
      ZAP relief was significantly shorter and the incidence of PHN was significantly
      lower in the acute TFEI group than in the subacute TFEI group. Rate of medication
      discontinuation was significantly higher in the acute TFEI group than in the
      subacute TFEI group. CONCLUSIONS: Early application of TFEI in the acute phase of
      zoster can be a useful option for ZAP control and prevention of chronic
      neuropathic pain such as PHN.

PMID- 29051968
TI  - Impact of Surgical Lighting on Intraoperative Safety in Low-Resource Settings: A
      Cross-Sectional Survey of Surgical Providers.
AB  - BACKGROUND: Safe surgery requires high-quality, reliable lighting of the surgical
      field. Little is reported on the quality or potential safety impact of surgical
      lighting in low-resource settings, where power failures are common and equipment
      and resources are limited. METHODS: Members of the Lifebox Foundation created a
      novel, non-mandatory, 18-item survey tool using an iterative process. This was
      distributed to surgical providers practicing in low-resource settings through
      surgical societies and mailing lists. RESULTS: We received 100 complete
      responses, representing a range of surgical centres from 39 countries. Poor
      quality surgical field lighting was reported by 40% of respondents, with 32%
      reporting delayed or cancelled operations due to poor lighting and 48% reporting
      electrical power failures at least once per week. Eighty per cent reported the
      quality of their surgical lighting presents a patient safety risk with 18% having
      direct experience of poor-quality lighting leading to negative patient outcomes.
      When power outages occur, 58% of surgeons rely on a backup generator and 29%
      operate by mobile phone light. Only 9% of respondents regularly use a surgical
      headlight, with the most common barriers reported as unaffordability and poor in
      country suppliers. CONCLUSIONS: In our survey of surgeons working in low-resource
      settings, a majority report poor surgical lighting as a major risk to patient
      safety and nearly one-third report delayed or cancelled operations due to poor
      lighting. Developing and distributing robust, affordable, high-quality surgical
      headlights could provide an ideal solution to this significant surgical safety
      issue.

PMID- 29051969
TI  - [Use of unmanned drones to deliver an automated external defibrillator for out-of
      hospital cardiac arrest].

PMID- 29051970
TI  - Construction of an ultra-high density consensus genetic map, and enhancement of
      the physical map from genome sequencing in Lupinus angustifolius.
AB  - KEY MESSAGE: An ultra-high density genetic map containing 34,574 sequence-defined
      markers was developed in Lupinus angustifolius. Markers closely linked to nine
      genes of agronomic traits were identified. A physical map was improved to cover
      560.5 Mb genome sequence. Lupin (Lupinus angustifolius L.) is a recently
      domesticated legume grain crop. In this study, we applied the restriction-site
      associated DNA sequencing (RADseq) method to genotype an F9 recombinant inbred
      line population derived from a wild type * domesticated cultivar (W * D) cross. A
      high density linkage map was developed based on the W * D population. By
      integrating sequence-defined DNA markers reported in previous mapping studies, we
      established an ultra-high density consensus genetic map, which contains 34,574
      markers consisting of 3508 loci covering 2399 cM on 20 linkage groups. The
      largest gap in the entire consensus map was 4.73 cM. The high density W * D map
      and the consensus map were used to develop an improved physical map, which
      covered 560.5 Mb of genome sequence data. The ultra-high density consensus
      linkage map, the improved physical map and the markers linked to genes of
      breeding interest reported in this study provide a common tool for genome
      sequence assembly, structural genomics, comparative genomics, functional
      genomics, QTL mapping, and molecular plant breeding in lupin.

PMID- 29051971
TI  - Fine mapping of the Brassica napus Bnsdt1 gene associated with determinate growth
      habit.
AB  - KEY MESSAGE: The newly discovered determinate plant growth habit of Brassica
      napus is a potential trait that might contribute to the genetic improvement of
      rapeseed. Brassica napus is an important species of rapeseed and has an
      indeterminate growth habit. However, a determinate inflorescence strain (4769)
      has been discovered among doubled haploid (DH) lines obtained from a spring B.
      napus * winter B. napus cross. We assessed the effect of the determinate growth
      habit on agronomic traits. The results showed that determinacy is beneficial for
      reducing plant height and flowering time, advancing maturity and maintaining
      productivity. We also investigated the inheritance of determinacy. A genetic
      analysis revealed that the phenotype of the determinate trait is controlled by
      one recessive gene, Bnsdt1. Mapping of the Bnsdt1 gene was subsequently conducted
      in BC1 and BC3 populations derived from combination 2014 * 4769. The results
      showed that the Bnsdt1 gene could be delimited to a region of approximately 220
      kb, between 16,627 and 16,847 kb on A10. Within the target region, whole-genome
      re-sequencing identified two candidate regions (16,628-16,641 and 16,739-16,794
      kb) of approximately 68 kb. A Blast analysis of the two candidate intervals found
      that BnaA10g26300D/GSBRNA2T00136426001 (BnTFL1) is homologous to the TFL1 gene of
      A. thaliana. Subsequently, quantitative reverse transcription (qRT)-PCR revealed
      that BnTFL1 was specifically expressed in the shoot apex. Collectively, the
      results of expression analysis provide preliminary evidence that BnTFL1 is a
      candidate gene for the inflorescence trait in 4769.

PMID- 29051972
TI  - miR-96-5p prevents hepatic stellate cell activation by inhibiting autophagy via
      ATG7.
AB  - : Activation of hepatic stellate cell (HSC), which is the main source of
      extracellular matrix, plays a pivotal role in liver fibrogenesis. Autophagy of
      hepatic stellate cell has been recently implicated in liver fibrosis, but the
      regulation of hepatic stellate cell autophagy during this process remains poorly
      understood. Here, we first identified miR-96-5p as an aberrantly expressed miRNA
      in fibrotic liver tissues. Next, we transfected miR-96-5p mimic into human
      hepatic stellate cell line LX-2 and observed decreased protein and mRNA levels of
      alpha-SMA and Col1A1. In addition, transfection of miR-96-5p mimic significantly
      reduced autophagy activity of LX-2 cells, while transfection of miR-96-5p
      inhibitor promoted LX-2 cell autophagy. Moreover, autophagy-related protein 7
      (ATG7) was predicted as a potential target of miR-96-5p and luciferase assay
      confirmed its direct interaction with miR-96-5p. Finally, reintroduction of ATG7
      into LX-2 cells reversed miR-96-5p-mediated inhibition of autophagy as well as
      alpha-SMA and Col1A1 expression. In conclusion, we demonstrated that miR-96-5p
      can inhibit hepatic stellate cell activation by blocking autophagy via ATG7.
      These findings provide new insight into the development of miRNA-based anti
      fibrotic strategies. KEY MESSAGES: * Altered miRNA expression profile is observed
      in fibrotic liver tissues. * miR-96-5p can inhibit HSC activation. * Autophagy of
      HSC is repressed by miR-96-5p during activation. * ATG7 is a direct target of miR
      96-5p. * ATG7 can rescue miR-96-5p-mediated inhibition of autophagy and HSC
      activation.

PMID- 29051973
TI  - IGRA testing in patients with immune-mediated inflammatory diseases: which
      factors influence the results?
AB  - Diagnosis of latent tuberculosis infection in patients with immune-mediated
      inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test
      reliability could be impaired by immunosuppression. We retrospectively analyzed
      the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs
      seen at the Department of Internal Medicine of Son Llatzer Hospital, Palma de
      Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate
      results. During the study period (2008-2015), 520 patients met the inclusion
      criteria. Factors associated with indeterminate QFT-G-IT results in a univariate
      analysis were inflammatory bowel disease, disease activity, lymphopenia, and
      medium-to-high doses of corticosteroids. In a subsequent multivariate analysis,
      only lymphopenia (defined as < 1500 cells) was associated with indeterminate QFT
      G-IT results. Lymphocyte count was the only factor independently associated with
      an increased number of indeterminate QFT-G-IT results in patients with different
      autoimmune diseases. Others factors such as the use of medium-to-high doses of
      corticosteroids should be considered before testing with QFT-G-IT.

PMID- 29051974
TI  - Cardiac disease in familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is an autoinflammatory disease manifested by
      inflammatory attacks of peritonitis, pleuritis, pericarditis accompanied by fever
      and arthritis. Mutations of MEFV gene results in pyrin dysfunction, which causes
      uncontrolled interleukin-1 beta production and triggers the inflammatory attacks.
      Inflammation persists even during attack-free periods in one-third of the FMF
      patients. Findings of elevated proinflammatory cytokine patterns during remission
      as well as inflammatory attacks indicate the continuous subclinical disease
      activity and inflammation. Chronic inflammation was thought to be related to the
      cardiovascular risk in FMF patients. Main cardiac manifestations reported in FMF
      are pericarditis, idiopathic recurrent pericarditis, pericardiac tamponade,
      coronary heart disease and abnormal cardiovascular reactivity. Cardiac
      involvement in FMF may often be related to secondary AA amyloidosis. Deposition
      of amyloid may lead to cardiovascular morbidity and mortality in FMF patients.
      Associations of several vasculitic disorders such as Immunoglobulin A-associated
      vasculitis, polyarteritis nodosa and Behcet's disease are common in FMF.
      Appropriate prophylactic treatment with colchicine is recommended to prevent from
      cardiovascular risks. For those resistant to colchicine, IL-1 inhibitor agents
      can be used. Associated vasculitis should be treated with immunosuppressive
      agents. This review article aims to compile information about cardiac disease in
      FMF and refer to recent studies on the topic.

PMID- 29051975
TI  - Impact of lesion complexity on long-term vascular response to cobalt-chromium
      everolimus-eluting stent: five-year follow-up optical coherence tomography study.
AB  - The impact of lesion complexity on long-term vascular response to cobalt-chromium
      everolimus-eluting stent (CoCrEES) remains unclear. We sought to evaluate them
      using optical coherence tomography (OCT). A total of 47 patients with 58 lesions
      treated only with CoCrEES and no target-vessel events within 5 years after
      implantation were prospectively enrolled and underwent 5-year follow-up OCT.
      Quantitative parameters and qualitative characteristics of the neointima were
      evaluated using multilevel logistic or linear regression models with random
      effects at three levels: lesion, cross-section (CS), and strut. According to the
      lesion complexity, the lesions were classified into the two groups: the complex
      lesion (CL) and non-CL group. The CL was defined as having at least 1 high-risk
      feature such as acute coronary syndrome lesion, lesion length > 20 mm, severe
      calcification requiring rotational atherectomy, and chronic total occlusion at
      the index procedure. A total of 11,034 struts (CL, n = 6240; non-CL, n = 4794)
      and 1202 (CL, n = 683; non-CL, n = 519) CSs were analyzed. The percentage of
      uncovered and malapposed struts did not differ significantly between the CL and
      non-CL groups (0.90 vs. 0.54%, P = 0.78; 0.56 vs. 0.10%, P = 0.16, respectively).
      The incidence of neoatherosclerosis was comparable between both groups in the CS-
      and lesion-level analysis (3.5 vs. 4.6%, P = 0.91; 32.0 vs. 24.2%, P = 0.52,
      respectively). At 5 years, CoCrEES shows an excellent vascular healing and
      similar frequency of neoatheroslerosis in patients without target-vessel events,
      regardless of the lesion complexity.

PMID- 29051977
TI  - [Industry 4.0 in pathology : Process optimization by lean management].

PMID- 29051976
TI  - Late gadolinium enhancement on cardiac magnetic resonance imaging is associated
      with coronary endothelial dysfunction in patients with dilated cardiomyopathy.
AB  - Myocardial fibrosis and coronary endothelial dysfunction are important
      determinants of outcome in patients with heart failure. However, the relationship
      of these factors in patients with dilated cardiomyopathy (DCM) is not fully
      understood. This study aimed to investigate the relationship between endothelium
      dependent coronary vasomotor abnormality and late gadolinium enhancement (LGE) on
      cardiac magnetic resonance imaging (CMR) in patients with DCM. We examined 38
      consecutive patients with DCM. All patients underwent CMR and the acetylcholine
      (ACh) provocation test using cardiac catheterization. During the ACh provocation
      test, we sampled blood simultaneously from the coronary sinus and aortic root to
      compare lactate concentrations, and quantified coronary blood flow volume using
      an intracoronary Doppler-tipped guidewire. LGE was detected in 17 (44.7%)
      patients. The lactate extraction ratio (LER) in the ACh provocation test was
      significantly decreased in the LGE-positive group (before vs after ACh, 18.6 +/-
      13.6 vs - 13.3 +/- 24.8%; p < 0.001) and in the LGE-negative group (before vs
      after ACh, 14.2 +/- 19.5 vs 3.3 +/- 16.2%; p = 0.02). The rate of patients with
      an LER < 0% (indicating myocardial lactate production due to myocardial ischemia)
      was significantly higher in the LGE-positive group than in the LGE-negative group
      [12 (70.6%) vs 7 (33.3%); p = 0.02]. Multivariable logistic regression analysis
      showed that a post-ACh LER < 0% was a significant predictor of LGE positivity
      (odds ratio 7.75; 95% confidence interval 1.37-43.68; p = 0.02). In conclusion,
      ACh-provoked coronary vasomotor abnormality is associated with myocardial
      fibrosis in patients with DCM. These results suggest that coronary endothelial
      dysfunction is involved in myocardial fibrosis and worsening heart failure
      concomitant with DCM.

PMID- 29051979
TI  - Vinchon's responses raise additional questions about the shaken baby-study.

PMID- 29051978
TI  - Symptom prevalence, bother, and treatment satisfaction in men with lower urinary
      tract symptoms in Southeast Asia: a multinational, cross-sectional survey.
AB  - PURPOSE: The overall objective of the survey was to systematically examine
      patients' perspectives on lower urinary tract symptoms (LUTS) and their treatment
      in Southeast Asia. METHODS: A multinational cross-sectional survey involving
      adult men seeking consultation at urology outpatient clinics because of LUTS in
      Southeast Asia was conducted using convenience sampling. Self-reported
      prevalence, bother, treatment and treatment satisfaction of selected LUTS
      including urgency, nocturia, slow stream, and post-micturition dribble were
      evaluated. RESULTS: In total, 1535 eligible patients were enrolled in the survey.
      A majority of respondents were aged 56-75 years, not employed, and had not
      undergone prostate operation before. Overall, the self-reported prevalence of
      nocturia was 88% (95% CI 86-90%), slow stream 61% (95% CI 59-63%), post
      micturition dribble 55% (95% CI 52-58%), and urgency 52% (95% CI 49-55%). There
      were marked differences in the country specific prevalence of LUTS complaints.
      Frequently, symptoms coexisted and were combined with nocturia. More than half of
      patients felt at least some degree of bother from their symptoms: 61% for
      urgency, 57% for nocturia, 58% for slow stream, and 60% for post-micturition
      dribble. Before seeing the present urologists, nearly half of patients have
      received some form of prescribed treatment and more than 80% of patients
      indicated they would like to receive treatment. CONCLUSION: Men who sought
      urologist care for LUTS often presented with multiple symptoms. Nocturia emerged
      as the most common symptom amongst the four core symptoms studied.

PMID- 29051980
TI  - Genomic Analysis of Bacillus sp. Strain B25, a Biocontrol Agent of Maize Pathogen
      Fusarium verticillioides.
AB  - Bacillus sp. B25 is an effective biocontrol agent against the maize pathogenic
      fungus Fusarium verticillioides (Fv). Previous in vitro assays have shown that
      B25 has protease, glucanase, and chitinase activities and siderophores
      production; however, specific mechanisms by which B25 controls Fv are still
      unknown. To determine the genetic traits involved in biocontrol, B25 genome was
      sequenced and analyzed. B25 genome is composed of 5,113,413 bp and 5251 coding
      genes. A multilocus phylogenetic analysis (MLPA) suggests that B25 is closely
      related to the Bacillus cereus group and a high percentage (70-75%) of the
      genetic information is conserved between B25 and related strains, which include
      most of the genes associated to fungal antagonism. Some of these genes are shared
      with some biocontrol agents of the Bacillus genus and less with Pseudomonas and
      Serratia strains. We performed a genomic comparison between B25 and five Bacillus
      spp., Pseudomonas and Serratia strains. B25 contains genes involved in a wide
      variety of antagonistic mechanisms including chitinases, glycoside hydrolases,
      siderophores, antibiotics, and biofilm production that could be implicated in
      root colonization. Also, 24 genomic islands and 3 CRISPR sequences were
      identified in the B25 genome. This is the first comparative genome analysis
      between strains belonging to the B. cereus group and biocontrol agents of
      phytopathogenic fungi. These results are the starting point for further studies
      on B25 gene expression during its interaction with Fv.

PMID- 29051982
TI  - Irreversible electroporation of pancreatic adenocarcinoma: a primer for the
      radiologist.
AB  - Irreversible electroporation (IRE) is increasingly used for the ablation of
      unresectable locally advanced pancreatic adenocarcinoma. Unlike other ablation
      technologies that cannot be safely used around critical vasculature or ducts for
      risk of thermal damage, IRE uses high-voltage pulses to disrupt cellular
      membranes. This causes cell death by apoptosis and inflammation. IRE has been
      deployed by both open and percutaneous approaches. Generator parameters are the
      same for both approaches, and settings are pancreas specific. Variations in
      settings, probe placement, and probe exposure can result in thermal damage or
      reversible electroporation and resultant treatment failure, morbidity, or
      mortality. When used properly, IRE appears to improve overall survival and local
      recurrence, but does not influence the rate of distant recurrence. However,
      studies of both open and percutaneous approaches have been relatively small, non
      controlled, and without appropriate comparisons. It is challenging for the
      radiologist to interpret treatment effects after IRE because of a dearth of
      guiding literature and pathologic correlates. This primer describes technical
      aspects, pathology correlates, post-IRE imaging, and outcomes for percutaneous
      and open approaches.

PMID- 29051981
TI  - Preoperative optimization of patients with inflammatory bowel disease undergoing
      gastrointestinal surgery: a systematic review.
AB  - PURPOSE: Surgical management of inflammatory bowel disease (IBD) is a challenging
      task. The aim of preoperative optimization (PO) is to decrease the risk of
      complications and reduce the length of postoperative stay. The aim of this study
      was to review and grade the available evidence, attain clear recommendations, and
      point out potential future research. METHODS: Studies were identified from
      electronic databases (PubMed, Embase, and Cochrane Library) and scanning
      reference lists in relevant papers. English-written studies examining PO in adult
      patients with IBD were included. Eight PO factors were investigated. RESULTS:
      Management of IBD is a multidisciplinary task. Steroid withdrawal is recommended
      while steroid stress dose is not recommended. Thiopurines appear to be safe, but
      it may be prudent to plan the procedure remotely from the last dose of an anti
      TNF agent. Nutritional risk screening is recommended to unveil and correct any
      malnutrition. Thrombosis prophylaxis prior to surgery is well supported by
      evidence while extended 4-week prophylaxis needs further research. Percutaneous
      ultrasound or CT-guided drainage for intra-abdominal abscesses is recommended,
      but it is unclear for how long supplementary antibiotics (ABs) should be used.
      Oral AB 24 h prior to open surgery might improve outcome if given as
      complementary to IV perioperative AB. Mechanical bowel preparation is not
      supported by evidence. Comorbidities must be treated accordingly prior to
      surgical intervention. Smoking cessation can be beneficial for wound healing.
      CONCLUSION: Multimodel PO intervention in IBD patients is recommended.

PMID- 29051983
TI  - Delayed manifestations of abdominal trauma: follow-up abdominopelvic CT in
      posttraumatic patients.
AB  - PURPOSE: Our study aims to investigate the frequency and patterns of delayed
      manifestations of abdominal and pelvic injuries which may not be identified or
      which fail to manifest on the initial abdominopelvic CT in posttraumatic
      patients. METHODS: For our institutional review board (IRB)-approved
      retrospective study, our hospital trauma registry was queried for patients with
      blunt multitrauma and Injury Severity Score (ISS) >= 16 between January 2010 and
      August 2016, yielding 3735 patients. A total of 203 patients received a follow-up
      abdominopelvic CT within six months from the initial scan and those with new
      findings on follow-up CT were identified. A retrospective blinded review of the
      initial CT examinations was performed by two experienced radiologists. The
      retrospective readings and original reports were compared to categorize the new
      abnormalities detected on follow-up CT scans. The categories included missed
      injuries, late presentations and sequelae of trauma, and complications of
      surgery, hospital admission, and invasive procedures. The patients' notes were
      reviewed for the clinical indications, time interval for repeat CT examination,
      and subsequent clinical management. The software used for statistical analysis of
      the extracted data was Microsoft Excel for Mac (version 15.33). RESULTS: Out of
      3735 patients, 203 patients received 232 follow-up abdominopelvic CTs. The
      average elapsed time between the initial CT and the follow-up CT was 15 +/- 27
      days. Evaluation for an abdominal fluid collection was the most common clinical
      indication, accounting for 40% of the total number (n = 243) of indications.
      Delayed manifestations and complications of trauma were present in 41 patients
      due to 47 abnormalities, most commonly related to solid organ injury, followed by
      abdominal collections and hematoma. Twenty-nine CT findings (62%) were only
      detectable on follow-up CT, while nine injuries (19%) were missed on initial CT.
      The findings on repeated CT warranted eight surgical and 15 interventional
      procedures. CONCLUSION: A small percentage of traumatic injuries may be
      unidentified or fail to manifest on the initial CT, resulting in delayed
      manifestations of abdominopelvic trauma, which may lead to subsequent
      readmission, delayed management, and more severe medical complications.

PMID- 29051984
TI  - Harnessing advances in computer simulation to inform policy and planning to
      reduce alcohol-related harms.
AB  - OBJECTIVES: Alcohol misuse is a complex systemic problem. The aim of this study
      was to explore the feasibility of using a transparent and participatory agent
      based modelling approach to develop a robust decision support tool to test
      alcohol policy scenarios before they are implemented in the real world. METHODS:
      A consortium of Australia's leading alcohol experts was engaged to
      collaboratively develop an agent-based model of alcohol consumption behaviour and
      related harms. As a case study, four policy scenarios were examined. RESULTS: A
      19.5 +/- 2.5% reduction in acute alcohol-related harms was estimated with the
      implementation of a 3 a.m. licensed venue closing time plus 1 a.m. lockout; and a
      9 +/- 2.6% reduction in incidence was estimated with expansion of treatment
      services to reach 20% of heavy drinkers. Combining the two scenarios produced a
      33.3 +/- 2.7% reduction in the incidence of acute alcohol-related harms,
      suggesting a synergistic effect. CONCLUSIONS: This study demonstrates the
      feasibility of participatory development of a contextually relevant computer
      simulation model of alcohol-related harms and highlights the value of the
      approach in identifying potential policy responses that best leverage limited
      resources.

PMID- 29051985
TI  - Insomnia and depression: risk factors for development of depression in male
      Japanese workers during 2011-2013.
AB  - OBJECTIVES: This 3-year cohort study was conducted to investigate the relation
      between insomnia and development of depression in male workers, and to clarify
      the association between the severity of insomnia and the onset of depression.
      METHODS: Self-administered questionnaire surveys on depression and insomnia were
      conducted on male workers for 3 years. Depression was assessed with the Center
      for Epidemiologic Studies Depression Scale (CES-D), and insomnia was examined
      using the Athens Insomnia Scale (AIS). The analysis was done with 840 men who had
      no depression at baseline. RESULTS: Depression symptoms were newly found in 113
      men during this study. Cox regression analyses showed that people with insomnia
      (AIS score of >= 1) at baseline had about a 7 times greater risk for onset of
      depression. Furthermore, compared with those with AIS score of 0 (no insomnia),
      people with AIS score of 1-3 had a 5.2-fold greater risk of depression and those
      with a score of 4 or higher indicated about tenfold greater risk. CONCLUSIONS: A
      new finding was that the risk for onset of depression increased with the severity
      of insomnia.

PMID- 29051986
TI  - The relationship between fatty liver index and bone mineral density in Koreans:
      KNHANES 2010-2011.
AB  - : Analyses using a nationally representative cohort have revealed that high fatty
      liver index (FLI) is associated with low bone mineral density (BMD) regardless of
      insulin resistance in men, thereby supporting the deteriorated bone metabolism in
      nonalcoholic fatty liver disease (NAFLD). INTRODUCTION: NAFLD is linked to
      deteriorated bone health. We investigated the association of FLI, a scoring model
      for NAFLD, with BMD. METHODS: This was a population-based, cross-sectional study
      from the Korea National Health and Nutrition Examination Surveys including 4264
      Koreans (1908 men and 2356 women). FLI was calculated using body mass index,
      waist circumference, serum triglyceride, and gamma-glutamyltranspeptidase level.
      Insulin resistance was evaluated using the homeostasis model assessment-estimated
      insulin resistance (HOMA-IR) index. BMD was measured using dual-energy X-ray
      absorptiometry at the lumbar spine, total hip, femoral neck, and whole body.
      RESULTS: Men had a higher FLI than women, while the HOMA-IR index was similar
      between men and women. The significant association between FLI and BMD was
      observed only in men, but not in women. FLI was negatively correlated with total
      hip, femoral neck, and whole body BMD in men after adjusting for all potential
      confounders, including HOMA-IR (P < 0.001 to 0.010). Lumbar spine, total hip,
      femoral neck, and whole body BMD in men showed a decreasing trend as the FLI
      tertile increased after adjusting for all potential confounders, including HOMA
      IR (P for trends < 0.001 to 0.034). In men aged 50 years or older, odds ratios
      for combined osteopenia and osteoporosis increased across increasing FLI tertiles
      after adjusting for confounders (P for trends < 0.011 to 0.029). CONCLUSION:
      NAFLD is associated with low bone density regardless of insulin resistance in
      men. These findings suggest an undiscovered direct link between liver and bone
      that increases the risk of osteoporosis in men with NAFLD.

PMID- 29051987
TI  - 1-Ethyl-3-methylimidazolium tolerance and intracellular lipid accumulation of 38
      oleaginous yeast species.
AB  - Pretreatment with ionic liquids (IL) such as 1-ethyl-3-methylimidazolium chloride
      or acetate is an effective method for aiding deconstruction of lignocellulosic
      biomass; however, the residual IL remaining in hydrolysates can be inhibitory to
      growth of ethanologenic or oleaginous yeasts that have been examined in the
      literature. The aim of this study was to identify oleaginous yeasts that are
      tolerant of the IL [C2C1Im][OAc] and [C2C1Im]Cl using 45 strains belonging to 38
      taxonomically diverse species within phyla Ascomycota and Basidiomycota. Yeasts
      were cultivated in laboratory medium supplemented with 0, 2, or 4% IL in 96-well
      plates. The eight most tolerant strains were then cultivated in 10-mL media with
      no IL, 242mM [C2C1Im][OAc], or 242mM [C2C1Im]Cl. The effects of [C2C1Im]+
      exposure on cell mass production and lipid accumulation varied at the species and
      strain level. The acetate salt decreased cell biomass and lipid production more
      severely than did the chloride ion for six strains. Lipid output was not markedly
      different (2.1 vs. 2.3 g/L) in Yarrowia lipolytica UCDFST 51-30, but decreased
      from 5 to 65% in other yeasts. An equimolar concentration of the chloride salt
      resulted in much milder effects, from 25% decrease to 66% increase in lipid
      output. The highest lipid outputs in this media were 8.3 and 7.9 g/L produced by
      Vanrija humicola UCDFST 10-1004 and UCDFST 12-717, respectively. These results
      demonstrated substantial lipid production in the presence of [C2C1Im]Cl at
      concentrations found in lignocellulosic hydrolysates, and thus, these two strains
      are ideal candidates for further investigation.

PMID- 29051988
TI  - Starvation- and xenobiotic-related transcriptomic responses of the sulfanilic
      acid-degrading bacterium, Novosphingobium resinovorum SA1.
AB  - Novosphingobium resinovorum SA1 was the first single isolate capable of degrading
      sulfanilic acid, a widely used representative of sulfonated aromatic compounds.
      The genome of the strain was recently sequenced, and here, we present whole-cell
      transcriptome analyses of cells exposed to sulfanilic acid as compared to cells
      grown on glucose. The comparison of the transcript profiles suggested that the
      primary impact of sulfanilic acid on the cell transcriptome was a starvation-like
      effect. The genes of the peripheral, central, and common pathways of sulfanilic
      acid biodegradation had distinct transcript profiles. The peripheral genes
      located on a plasmid had very high basal expressions which were hardly
      upregulated by sulfanilic acid. The genomic context and the codon usage
      preference of these genes suggested that they were acquired by horizontal gene
      transfer. The genes of the central pathways were remarkably inducible by
      sulfanilic acid indicating the presence of a substrate-specific regulatory system
      in the cells. Surprisingly, the genes of the common part of the metabolic pathway
      had low and sulfanilic acid-independent transcript levels. The approach applied
      resulted in the identification of the genes of proteins involved in auxiliary
      processes such as electron transfer, substrate and iron transports, sulfite
      oxidases, and sulfite transporters. The whole transcriptome analysis revealed
      that the cells exposed to xenobiotics had multiple responses including general
      starvation-like, substrate-specific, and substrate-related effects. From the
      results, we propose that the genes of the peripheral, central, and common parts
      of the pathway have been evolved independently.

PMID- 29051990
TI  - Clinicopathologic implications of CD8+/Foxp3+ ratio and miR-574-3p/PD-L1 axis in
      spinal chordoma patients.
AB  - Currently, little is known about the interactions between microRNAs (miRNAs) and
      the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the
      immune milieu in chordoma prognosis are limited. We aimed to analyze the
      relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating
      lymphocytes (TILs) and clinicopathological features of spinal chordoma patients.
      PD-L1 expression and TILs (including Foxp3+, CD8+, PD-1+ and PD-L1+) were
      assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma
      patients. MiRNAs microarray and bioinformatical analysis were used to identify
      miRNAs potentially regulating PD-L1 expression, which were further validated by
      quantitative RT-PCR. miR-574-3p was identified to potentially regulate PD-L1
      expression in chordoma, which inversely correlated with PD-L1. Positive PD-L1
      expression on tumor cells was associated with advanced stages (P = 0.041) and
      TILs infiltration (P = 0.005), whereas decreased miR-574-3p level correlated with
      higher muscle invasion (P = 0.012), more severe tumor necrosis (P = 0.022) and
      poor patient survival. Importantly, a patient subgroup with PD-L1+/miR-574-3plow
      chordoma phenotype was significantly associated with worse local recurrence-free
      survival (LRFS) (P = 0.026). PD-1+ TILs density was associated with surrounding
      muscle invasion (P = 0.014), and independently portended poor LRFS (P = 0.040),
      while PD-L1+ TILs showed tendencies of less aggressive clinical outcomes.
      Multivariate analysis of OS only found CD8+/Foxp3+ ratio to be independent
      prognostic factor (P = 0.022). These findings may be useful to stratify patients
      into prognostic groups and provide a rationale for the use of checkpoint blockade
      therapy, possibly by administering miR-574-3p mimics, in spinal chordoma.

PMID- 29051989
TI  - A randomized phase I study to evaluate the safety, tolerability, pharmacokinetics
      and food-effect of Iguratimod in healthy adult volunteers.
AB  - OBJECTIVE: The aim of this study was to investigate the safety, maximum tolerated
      dose and pharmacokinetics (PK) of iguratimod and the effect of food on PK
      parameters in healthy adult volunteers. METHODS: This phase 1 study consisted of
      four parts. Part 1 was a single-ascending dose (3.125, 6.25, 12.5, 25, 50, 75 mg)
      study to assess the maximum tolerated dose and safety of iguratimod. Part 2 was a
      single-ascending dose study to analyze the pharmacokinetic (PK) parameters of
      iguratimod; subjects were divided into three groups, with each group receiving
      iguratimod at a different dose (25, 50 or 75 mg). Part 3 was designed to compare
      the pharmacokinetic parameters of iguratimod between single-dose and multiple
      dose administration; subjects were divided into two groups, with one group
      receiving a single dose of 50 mg on day 1 and the other group receiving a
      multiple dose of 50 mg, once every day, until a stable plasma concentration had
      been achieved. The aim of part 4 was to evaluate the effect of food on the
      pharmacokinetic parameters of iguratimod; subjects were divided into two groups,
      namely a fed group and a fasted group, with each group receiving a single 50 mg
      dose of iguratimod on day 1. Following a 14-day washout period, the two groups
      were crossed-over and received a single dose of 50 mg iguratimod on day 15.
      RESULTS: In part 1 of the study, iguratimod at doses ranging from 3.125 to 50 mg
      were well tolerated, with most adverse effects (AEs) being mild; no severe AEs
      occurred. In part 2, there were no significant differences in Tmax, T1/2, Ka and
      V/F among volunteers receiving doses of 25, 50 and 75 mg iguratimod. The Cmax and
      AUC0-last in volunteers receiving 75 mg iguratimod were higher than those in
      volunteers receiving 25 and 50 mg. The Cmax was linear from 25 to 75 mg, with a
      correlation coefficient (r 2) of 0.9808. The AUC0-last was also linear from 25 to
      75 mg, with an r 2 of 0.9839. In part 3, in subjects receiving multiple doses of
      50 mg, the T1/2 was 10.25 h, Tmax was 3.63 h, Cmax was 1.88 mg/L, AUC0-last was
      31.88 mg/L h, Vd was 1.16 L and Ka was 0.87 1/h.There were no significant
      differences in the Cmax, AUC0-last, Ka and V/F between the single-dose and
      multiple-dose groups; there were, however, significant differences in Tmax and
      T1/2 between the two groups. In part 4, there were no significant differences in
      T1/2, AUC0-last, Ka and V/F between the fed group and fasted group; however, food
      may promote the absorption of iguratimod. CONCLUSIONS: The maximum tolerated dose
      for iguratimod was confirmed to be 50 mg. The ingestion of food was able to
      increase the peak concentration of iguratimod and shorten the time to peak
      concentration. Therefore, based on our results, iguratimod can be administered
      with food. The PK profile and metabolic effects of iguratimod support further
      clinical development for its application in treating autoimmune diseases.

PMID- 29051991
TI  - Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after
      chemoradiotherapy for esophageal cancer : A retrospective study and literature
      review.
AB  - BACKGROUND: For esophageal cancer patients treated with neoadjuvant
      chemoradiotherapy (nCRT), restaging using F-18-fluorodeoxyglucose (FDG) positron
      emission tomography computed tomography (PET-CT) following nCRT can detect
      interval metastases, including liver metastases, in almost 10% of patients.
      However, in clinical practice, focal FDG liver uptake, unrelated to liver
      metastases, is observed after chemoradiotherapy. This radiation-induced liver
      injury (RILI) can potentially lead to overstaging. METHODS: A systematic search
      for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was
      performed in the electronic reports from all PET-CT scans made between 2006 and
      2015 in our hospital. Additional data about potential cases were obtained from
      the electronic medical records. A literature review of RILI was also performed.
      RESULTS: Of 205 patients undergoing nCRT, 6 cases with localized increased FDG
      uptake in the caudate or left liver lobe following nCRT for esophageal cancer
      were identified. None of these patients had signs of liver metastases with
      additional imaging, during surgery, on biopsy, or during follow-up (range 11-46
      months). At our institute, the incidence of RILI after neoadjuvant
      chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is
      described in about 8% of patients at the time of restaging. FDG-avid lesions
      occur in the high radiation dose area, usually corresponding to the caudate or
      left liver lobe. CONCLUSIONS: FDG accumulation in the caudate or left liver lobe
      after CRT in the area that received a high radiation dose may be caused by
      metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is
      crucial to avoid misinterpretation and overstaging.

PMID- 29051993
TI  - Treatment-related sinusoidal obstruction syndrome in children with de novo acute
      lymphoblastic leukemia during intensification.
AB  - PURPOSE: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive
      disease, has been described following treatment of acute lymphoblastic leukemia
      (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies
      incorporating daily 6-TG into maintenance chemotherapy demonstrated a high
      incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG
      continues to be used as a single, 14-day burst during intensification; however,
      SOS associated with brief courses of 6-TG is poorly described. We aim to describe
      this rare though clinically significant phenomenon. METHODS: Children with 6-TG
      related SOS were retrospectively identified from 680 de novo patients with ALL at
      Texas Children's Cancer Center over 8 years. Clinical characteristics and
      outcomes are described. RESULTS: Ten (1.5%) patients were identified with SOS. No
      predominant sex, ethnicity, or race was noted. SOS was diagnosed 16.5 (6-42) days
      from starting 6-TG. Isolated thrombocytopenia (IT) was noted in 9/10 patients and
      presented a median of 5 days prior to SOS. Refractoriness to platelet
      transfusions was noted in 8/10 patients, presenting a median of 2 days prior to
      SOS. Most patients were otherwise clinically stable outpatients upon presenting
      with IT or transfusion refractoriness. Fever was noted in 7/10 patients at
      diagnosis and 6/10 had documented or suspected infection within 14 days of SOS.
      Two patients died, while eight fully recovered. Intermediate thiopurine
      methyltransferase genotype was noted in 5/8 patients with data available.
      CONCLUSION: SOS following short courses of 6-TG in DI is clinically distinct from
      SOS following prolonged courses of 6-TG in maintenance, particularly in its early
      presentation and outcomes.

PMID- 29051992
TI  - Adverse outcome pathways: opportunities, limitations and open questions.
AB  - Adverse outcome pathways (AOPs) are a recent toxicological construct that
      connects, in a formalized, transparent and quality-controlled way, mechanistic
      information to apical endpoints for regulatory purposes. AOP links a molecular
      initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way
      specified by key event relationships (KER). Although this approach to formalize
      mechanistic toxicological information only started in 2010, over 200 AOPs have
      already been established. At this stage, new requirements arise, such as the need
      for harmonization and re-assessment, for continuous updating, as well as for
      alerting about pitfalls, misuses and limits of applicability. In this review, the
      history of the AOP concept and its most prominent strengths are discussed,
      including the advantages of a formalized approach, the systematic collection of
      weight of evidence, the linkage of mechanisms to apical end points, the
      examination of the plausibility of epidemiological data, the identification of
      critical knowledge gaps and the design of mechanistic test methods. To prepare
      the ground for a broadened and appropriate use of AOPs, some widespread
      misconceptions are explained. Moreover, potential weaknesses and shortcomings of
      the current AOP rule set are addressed (1) to facilitate the discussion on its
      further evolution and (2) to better define appropriate vs. less suitable
      application areas. Exemplary toxicological studies are presented to discuss the
      linearity assumptions of AOP, the management of event modifiers and compensatory
      mechanisms, and whether a separation of toxicodynamics from toxicokinetics
      including metabolism is possible in the framework of pathway plasticity.
      Suggestions on how to compromise between different needs of AOP stakeholders have
      been added. A clear definition of open questions and limitations is provided to
      encourage further progress in the field.

PMID- 29051994
TI  - Telotristat ethyl: proof of principle and the first oral agent in the management
      of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome
      diarrhea.
AB  - INTRODUCTION: Metastatic neuroendocrine tumors (NETs) are associated with
      carcinoid syndrome that is typically characterized by diarrhea, cutaneous
      flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves
      the symptom burden but a significant proportion of patients stop responding to
      SSA therapy eventually. Novel agents with the potential to effectively control
      the symptoms are urgently needed. METHODS: This article reviews an in-depth
      analysis of the phase I-III clinical trials determining the clinical rationale
      for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients
      with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome.
      DISCUSSION: Telotristat ethyl has already been approved for the treatment of
      inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on
      SSA therapy. Results from multiple phase I-III clinical studies of telotristat
      ethyl therapy have reported a significant decrease in the daily bowel movement
      frequency, increase in quality of life and the subsequent decrease in annual
      health costs related to carcinoid syndrome symptoms in NET patients. FUTURE
      DIRECTIONS: The associated decrease in urinary 5-hydroxyindoleacetic acid (u5
      HIAA) provides evidence that telotristat ethyl effectively decreases serotonin
      production, and therefore, offers a rationale to investigate this agent to
      mitigate serotonin-mediated complications in this patient population, especially
      cardiac valvular disease or mesenteric fibrosis.

PMID- 29051995
TI  - Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue
      sarcoma patients: opportunities for dose optimization.
AB  - BACKGROUND: Pazopanib is an angiogenesis inhibitor approved for the treatment of
      renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical
      trial demonstrated a relationship between pazopanib trough concentrations (Cmin)
      and treatment efficacy. The aim of this study was to explore the pharmacokinetics
      and exposure-survival relationships of pazopanib in a real-world patient cohort.
      PATIENTS AND METHODS: Renal cell cancer and soft tissue sarcoma patients who had
      at least one pazopanib plasma concentration available were included. Using
      calculated Cmin values and a threshold of > 20 mg/L, univariate and multivariate
      exposure-survival analyses were performed. RESULTS: Sixty-one patients were
      included, of which 16.4% were underexposed (mean Cmin < 20 mg/L) using the 800 mg
      fixed-dosed schedule. In univariate analysis Cmin > 20 mg/L was related to longer
      progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n =
      35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p =
      0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142).
      In multivariate analysis Cmin > 20 mg/L was associated with hazard ratios of 0.25
      (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in
      a pooled analysis. CONCLUSION: This study confirms that pazopanib Cmin > 20 mg/L
      relates to better progression free survival in renal cancer and points towards a
      similar trend in sarcoma patients. Cmin monitoring of pazopanib can help identify
      patients with low Cmin for whom individualized treatment at a higher dose may be
      appropriate.

PMID- 29051996
TI  - Diffusion-Weighted MRI Stroke Volume Following Recanalization Treatment is
      Threshold-Dependent.
AB  - PURPOSE: Infarct lesion segmentation has been problematic as there are a wide
      range of relative and absolute diffusion-weighted imaging (DWI) and apparent
      diffusion coefficient (ADC) thresholds that have been used for this purpose. We
      examined differences of stroke lesion volume and evolution evaluated by magnetic
      resonance imaging (MRI) during the immediate post-treatment phase (<5 h) and at
      24 h. METHODS: In this study 33 acute ischemic stroke patients were imaged with
      MRI <5 h and 24 h post-reperfusion treatment. Lesion volumes were segmented on
      ADC maps and average DWI using literature cited absolute ADC and relative DWI
      thresholds. The segmented lesion volumes within both time points were compared
      and the absolute change in lesion volume (infarct growth) between the two time
      points was calculated and compared using Bland-Altman analysis. RESULTS: Lesion
      volumes differed significantly when different relative DWI or absolute ADC
      thresholds were used (p < 0.05), which held true for baseline as well as follow
      up lesions. The median absolute changes in lesion volume from baseline to follow
      up for ADC thresholds of 550 * 10-6 mm2/s, 600 * 10-6 mm2/s, 630 * 10-6 mm2/s and
      650 * 10-6 mm2/s were 3.5 ml, 4.2 ml, 4.5 ml, and 6.5 ml, respectively (p <
      0.05). Likewise, the median absolute changes in lesion volume from baseline to
      follow-up for DWI thresholds, k = 0.85, 1.28, 1.64, 1.96, and 2.7 were 10.1 ml,
      7.3 ml, 5.7 ml, 5.4 ml and 4.2 ml, respectively (p < 0.05). CONCLUSION: Absolute
      lesion volumes and changes in lesion volumes (infarct growth) measured after
      recanalization treatment were dependent on absolute ADC and relative DWI
      thresholds, which may have clinical significance. Standardization of techniques
      for measuring DWI lesion volumes requires immediate attention.

PMID- 29051997
TI  - Effect of repeated abstinence on chronic ethanol self-administration in the
      rhesus monkey.
AB  - RATIONALE: Abstinence-based approaches to treating alcohol use disorder (AUD) are
      highly prevalent, but abstinence from chronic drinking may exacerbate subsequent
      levels of alcohol intake in relapse. OBJECTIVE: Use a non-human primate model
      that encompasses a range of chronic voluntary ethanol drinking to isolate
      biological responses to repeated cycles of imposed abstinence as a function of
      baseline voluntary alcohol drinking levels. METHODS: Over a 26-month protocol,
      young adult male rhesus macaques were first induced to drink alcohol and then
      given continuous access to 4% (w/v) ethanol (n = 8) or water (n = 4) for
      approximately 14 months, followed by three 28- to 35-day abstinence phases, with
      3 months of ethanol access in between. Ethanol intake and blood ethanol
      concentration (BEC) were the primary dependent variables. Observational signs of
      physical dependence and circulating ACTH and cortisol were monitored. RESULTS:
      Prior to abstinence, stable, categorical, individual differences in voluntary
      ethanol intake under chronic access conditions were found. Following abstinence,
      categorical "non-heavy" drinking subjects increased drinking transiently
      (increased between 0.7 and 1.4 g/kg/day in first month after abstinence) but
      returned to baseline after 3 months. Categorical "heavy" drinkers, however,
      maintained drinking 1.0-2.6 g/kg above baseline for over 3 months following
      abstinence. Signs of physical dependence were rare, although huddling and social
      withdrawal increased in ethanol and control subjects. The most prominent effect
      on hormonal measures was heightened cortisol during abstinence that increased to
      a greater extent in ethanol subjects. CONCLUSION: Involuntary abstinence
      increases drinking in the absence of overt physical withdrawal symptoms, and
      heavy drinkers are more robustly affected compared to non-heavy drinkers.

PMID- 29051998
TI  - The Effect of Bisphenol A on Growth, Morphology, Lipid Peroxidation, Antioxidant
      Enzyme Activity, and PS II in Cylindrospermopsis raciborskii and Scenedesmus
      quadricauda.
AB  - To investigate the effect of bisphenol A (BPA) on Cylindrospermopsis raciborskii
      (Cyanobacteria) and Scenedesmus quadricauda (Chlorophyta), we grew the two
      species at BPA concentrations of 0, 0.1, 1, 2, 5, 10, and 20 mg/L and examined
      their growth, lipid peroxidation, antioxidant enzyme activity, and chlorophyll a
      fluorescence. The 96-h EC50 values (effective concentration causing 50% growth
      inhibition) for BPA in C. raciborskii and S. quadricauda were 9.663 +/- 0.047,
      and 13.233 +/- 0.069 mg/L, respectively. A significant reduction in chlorophyll a
      concentration was found in C. raciborskii and S. quadricauda when BPA
      concentrations were greater than 1 and 2 mg/L, respectively. Furthermore, F v/F
      m, DeltaF/F m', and qP decreased significantly at 10 mg/L BPA in C. raciborskii
      but started to decrease at 10 mg/L in S. quadricauda. The changes in chlorophyll
      fluorescence parameters (alpha, rETRmax) that were obtained from the rapid light
      response curves of both algae species showed similar responses to F v/F m,
      DeltaF/F m', and qP under BPA-induced stress. Values for all of the chlorophyll
      fluorescence parameters in S. quadricauda were higher than in C. raciborskii;
      however, the nonphotochemical quenching measured in C. raciborskii was
      considerably higher than it was in S. quadricauda. In addition, lipid
      peroxidation (determined as MDA content) and antioxidant enzyme activities (SOD
      and CAT) increased in both species as the BPA concentration increased. These
      results suggest that C. raciborskii is more sensitive to the effects of BPA than
      S. quadricauda and that photosystem II might be a target for the activity of BPA
      in vivo.

PMID- 29051999
TI  - Comparative Early Life Stage Toxicity of the African Clawed Frog, Xenopus laevis
      Following Exposure to Selected Herbicide Formulations Applied to Eradicate Alien
      Plants in South Africa.
AB  - The rise in pesticides application has increased the need for better
      understanding of their ecological impacts. The global amphibian declines, for
      example, have been positively correlated with pesticides use. The differential
      susceptibility in the developmental stages of amphibians to chemical substances
      are still largely unknown. We examined the 96-h differential toxicity responses
      of embryos, premetamorphic and transitional larval stage of Xenopus laevis, to
      six formulated aquatic herbicide products containing the active ingredients of
      diquat dibromide (Midstream), glufosinate ammonium (Basta), imazapyr (Arsenal),
      and three glyphosate formulations (Roundup, Kilo Max, and Environ Glyphosate).
      The results showed the premetamorphic stage as the most sensitive to the
      herbicides toxicity. This study confirmed that the developmental stage at which
      amphibian are exposed to contaminants is critical to their survival and that the
      chemical contamination hypothesis of the global decline of amphibians should
      continue to be considered. This establishment of the premetamorphic larval as
      sensitive toxicity representative for all developmental stages of X. laevis means
      that this stage could be used more extensively in pesticides toxicity
      assessments.

PMID- 29052000
TI  - Results of pectus excavatum correction using a minimally invasive approach with
      subxyphoid incision and three-point fixation.
AB  - OBJECTIVES: This study reviews the results of our previously described
      modification of the minimally invasive (Nuss) procedure for correction of pectus
      excavatum. It utilizes a subxyphoid incision with central fixation to maximize
      safe bar passage and minimize bar displacement. METHODS: Consecutive patients
      corrected with the modified Nuss procedure between 2010 and 2015 form the basis
      of this study. RESULTS: During the study period, 73 patients had correction of
      their pectus excavatum by the modified Nuss procedure, utilizing subxyphoid
      incision and central fixation. Average age was 14.3 (range 8-19). 54 patients
      were male, 19 female. The average Haller index was 4.3 (range 3.2-7.2). No
      episodes of cardiac perforation, hemothorax or significant pneumothorax were
      recorded. Bar displacement occurred in two patients (2.7%) with one late
      recurrence after bar removal. CONCLUSIONS: Our modification of the Nuss procedure
      is effective at preventing intrathoracic complications and cardiac perforation.
      Central fixation had a lower rate of bar displacement compared to published
      reports. Additional efforts are needed to further reduce bar displacement.

PMID- 29052001
TI  - Quail (Coturnix japonica) egg yolk bioactive components attenuate streptozotocin
      induced testicular damage and oxidative stress in diabetic rats.
AB  - INTRODUCTION: The testicular milieu is the machinery for the metabolism of
      testosterone in the male reproductive system. PURPOSE: The dysfunction of this
      highly regenerating system is inevitable in the condition of glucose imbalance as
      a result of insulin machinery impairment. Therefore, it is imperative to
      recommend dietary intervention for attenuating the testicular dysfunction and
      oxidative stress resulting from STZ-induction of diabetes. METHODS: STZ-induced
      diabetes (65 mg/kg, ip) was treated with QEYEM (50, 100 and 200 mg/kg/day) and
      quercetin (50 mg/kg/day) for 7weeks. In serum, glucose, testosterone, IL-6 and
      TNF-alpha levels were estimated, and in testis, tissues TBARS, sulfhydryl groups,
      nucleic acids and total protein (TP) levels were estimated. SOD, CAT and GST
      activities were also determined in testicular cells. Histopathological changes
      were evaluated in a cross-section of testis. RESULTS: Testosterone concentration
      was decreased while pro-inflammatory markers were increased in STZ-assaulted
      rats. Treatment using QEYEM of diabetic rats corrected assaults and reverse
      significantly the diabetic conditions. QEYEM-treated groups showed significant
      inhibition of TBARS levels and elevation of testicular GSH, NP-SH, total protein
      (TP) and nucleic acids-DNA and RNA levels. The QEYEM administration reversed the
      inhibited activities of SOD, CAT and GST in testicular cells in diabetic rats.
      The characterization of the extract carried out through HPLC analytical
      techniques revealed vitamins A, D and E concentrations of 0.645, 0.012 and 6.3
      mg/100 g, respectively. CONCLUSION: QEYEM supplementation to STZ-induced diabetic
      rats for seven (7) consecutive weeks is a potential intervention against
      testicular damage in adult diabetic rats, probably by decreasing oxidative
      stress.

PMID- 29052002
TI  - Molecular and clinical heterogeneity of adult diffuse low-grade IDH wild-type
      gliomas: assessment of TERT promoter mutation and chromosome 7 and 10 copy number
      status allows superior prognostic stratification.

PMID- 29052003
TI  - Accumulation of dysfunctional SOD1 protein in Parkinson's disease is not
      associated with mutations in the SOD1 gene.

PMID- 29052004
TI  - Hypoxia-regulated catecholamine secretion in chromaffin cells.
AB  - Adrenal catecholamine (CAT) secretion is a general physiological response of
      animals to environmental stressors such as hypoxia. This represents an important
      adaptive mechanism to maintain homeostasis and protect vital organs such as the
      brain. In adult mammals, CAT secretory responses are triggered by activation of
      the sympathetic nervous system that supplies cholinergic innervation of
      adrenomedullary chromaffin cells (AMC) via the splanchnic nerve. In the neonate,
      the splanchnic innervation of AMC is immature or absent, yet hypoxia stimulates a
      non-neurogenic CAT secretion that is critical for adaptation to extra-uterine
      life. This non-neurogenic, hypoxia-sensing mechanism in AMC is gradually lost or
      suppressed postnatally along a time course that parallels the development of
      splanchnic innervation. Moreover, denervation of adult AMC results in a gradual
      return of the direct hypoxia-sensing mechanism. The signaling pathways by which
      neonatal AMC sense acute hypoxia leading to non-neurogenic CAT secretion and the
      mechanisms that underlie the re-acquisition of hypoxia-sensing properties by
      denervated adult AMC, are beginning to be understood. This review will focus on
      current views concerning the mechanisms responsible for direct acute hypoxia
      sensing and CAT secretion in perinatal AMC and how they are regulated by
      innervation during postnatal development. It will also briefly discuss plasticity
      mechanisms likely to contribute to CAT secretion during exposures to chronic and
      intermittent hypoxia.

PMID- 29052005
TI  - Journal of Bone and Mineral Metabolism Best Paper Award 2017.

PMID- 29052007
TI  - What is a life worth living?

PMID- 29052006
TI  - Risk factors for and the prevention of acute kidney injury after abdominal
      surgery.
AB  - Postoperative acute kidney injury in patients undergoing abdominal surgery is not
      rare and often results in bad outcomes for patients. The incidence of
      postoperative acute kidney injury is hard to evaluate reliably due to its non
      unified definitions in different studies. Risk factors for acute kidney injury
      specific to abdominal surgery include preoperative renal insufficiency,
      intraabdominal hypertension, blood transfusion, bowel preparation, perioperative
      dehydration, contrast agent and nephrotoxic drug use. Among these, preoperative
      renal insufficiency is the strongest predictor of acute kidney injury. The peri
      operative management of high-risk patients should include meticulous selection of
      fluid solutions. Balanced crystalloid solutions and albumin are generally thought
      to be relatively safe, while the safety of hydroxyethyl starch solutions has been
      controversial. The purpose of the present review is to discuss the current
      knowledge regarding postoperative acute kidney injury in abdominal surgical
      settings to help surgeons make better decisions concerning the peri-operative
      management.

PMID- 29052009
TI  - Spatial and temporal variation in the range-wide cyclic dynamics of greater sage
      grouse.
AB  - Periodic changes in abundance, or population cycles, are common in a variety of
      species and is one of the most widely studied ecological phenomena. The strength
      of, and synchrony between population cycles can vary across time and space and
      understanding these patterns can provide insight into the mechanisms generating
      population cycles and their variability within and among species. Here, we used
      wavelet and spectral analysis on a range-wide dataset of abundance for the
      greater sage-grouse (Centrocercus urophasianus) to test for regional differences
      in temporal cyclicity. Overall, we found that most populations (11 of 15) were
      cyclic at some point in a 50-year time series (1965-2015), but the patterns
      varied over both time and space. Several peripheral populations demonstrated
      amplitude dampening or loss of cyclicity following population lows in the mid
      1990s. Populations through the core of the range in the Great and Wyoming Basins
      had more consistent cyclic dynamics, but period length appeared to shorten from
      10-12 to 6-8 years. In one time period, where cyclicity was greatest overall,
      increased pairwise population synchrony was correlated with cycle intensity. Our
      work represents a comprehensive range-wide assessment of cyclic dynamics and
      revealed substantial variation in temporal and spatial trends of cyclic dynamics
      across populations.

PMID- 29052008
TI  - Genome-wide analysis and expression profiling of PP2C clade D under saline and
      alkali stresses in wild soybean and Arabidopsis.
AB  - Protein phosphatase 2Cs (PP2Cs) belong to the largest protein phosphatase family
      in plants. Some members have been described as being negative modulators of plant
      growth and development, as well as responses to hormones and environmental
      stimuli. However, little is known about the members of PP2C clade D, which may be
      involved in the regulation of signaling pathways, especially in response to
      saline and alkali stresses. Here, we identified 13 PP2C orthologs from the wild
      soybean (Glycine soja) genome. We examined the sequence characteristics,
      chromosome locations and duplications, gene structures, and promoter cis-elements
      of the PP2C clade D genes in Arabidopsis and wild soybean. Our results showed
      that GsPP2C clade D (GsAPD) genes exhibit more gene duplications than AtPP2C
      clade D genes. Plant hormone and abiotic stress-responsive elements were
      identified in the promoter regions of most PP2C genes. Moreover, we investigated
      their expression patterns in roots, stems, and leaves. Quantitative real-time PCR
      analyses revealed that the expression levels of representative GsPP2C and AtPP2C
      clade D genes were significantly influenced by alkali and salt stresses,
      suggesting that these genes might be associated with or directly involved in the
      relevant stress signaling pathways. Our results established a foundation for
      further functional characterization of PP2C clade D genes in the future.

PMID- 29052010
TI  - Open versus closed treatment of distal tibia physeal fractures: a systematic
      review and meta-analysis.
AB  - AIMS: Distal tibia physeal fractures can lead to growth complications such as
      premature physeal closure (PPC), angular deformity and leg length discrepancy.
      The aim of our study was to systematically review the literature to assess
      whether open reduction and internal fixation (ORIF) is associated with lower
      rates of PPC compared to closed treatment. MATERIALS AND METHODS: We searched
      several databases from 1966 to 2016 for studies that evaluated ORIF versus closed
      treatment of distal tibia physeal fractures. We performed a meta-analysis using a
      random effects model to pool odds ratios (OR) for the comparison of PPC rate
      between children undergoing ORIF versus closed treatment. We also investigated
      the PPC rate in Salter-Harris (S-H) type I and II fractures. Descriptive,
      quantitative and qualitative data were extracted. RESULTS: Out of the 253
      articles identified, six retrospective cohort studies were eligible, with a total
      of 970 distal tibia physeal fractures. The pooled OR of PPC between ORIF and
      closed treatment showed no statistically significant difference [OR = 0.98, 95%
      confidence interval (CI) 0.48, 1.97; I 2 = 49.8%, p = 0.076]. No significant
      difference in the rate of PPC was detected in S-H type I and II fractures with
      ORIF and closed treatment [OR = 1.25, 95% CI 0.72, 2.16; I 2 = 32.1%, p = 0.22].
      CONCLUSIONS: The cumulative evidence at present does not indicate an association
      between the method of treatment of distal tibia physeal fractures and the risk of
      PPC. Both treatment types are feasible, but less surgical-related complications
      are associated with closed treatment. LEVEL OF EVIDENCE: III.

PMID- 29052011
TI  - The smartphone inclinometer: A new tool to determine elbow range of motion?
AB  - BACKGROUND: There are easily accessible tools on smartphones (APP) for measuring
      elbow range of motion (ROM). The purpose of this study is to evaluate the
      validity of a particular APP in determining elbow ROM in comparison with the
      commonly used goniometer (GON), surgeon estimation of range (EST) and measurement
      on X-ray (XR). METHODS: The study included 20 patients (40 elbows). Flexion,
      extension, pronation and supination were measured using three different methods:
      EST, GON and APP. Radiographic measurements were taken using the average humeral
      diaphysis axis and dorsal midthird of ulna in flexion and extension. RESULTS: The
      accuracy of the three different methods has been compared to GON using
      statistical analysis (ANOVA and paired samples test). There was no statistically
      significant difference for XR flexion measurement (mean of 2.8 degrees  +/- 1.5
      degrees ). The APP overestimated flexion (mean of 6.4 degrees  +/- 1.0 degrees ),
      and EST underestimated it (mean of - 7.9 degrees  +/- 1.1 degrees ). For
      extension, the mean difference was 2.8 degrees  +/- 0.7 degrees  for EST and -
      26.8 degrees  +/- 3.1 degrees  for XR. The APP method did not significantly
      differ from GON. Supination accuracy was greater with EST (2.7 degrees  +/- 1.7
      degrees ) than with APP (5.9 degrees  +/- 1.9 degrees ). There was no difference
      for pronation measurement with both EST and APP. CONCLUSIONS: This study is the
      first comparing four measurement techniques of elbow ROM. Our results showed that
      EST was only accurate for forearm rotation. The XR scored the best for flexion
      but is less reliable for extension. Surprisingly, compared to GON, APP did not
      correlate as we expected for flexion and supination, but the other methods were
      also inaccurate. We found APP to be very useful to measure complete arc of motion
      (difference between maximal flexion and maximal extension). LEVEL OF EVIDENCE:
      III, Retrospective review of a prospective cohort of elbow fracture patients:
      Diagnostic Study.

PMID- 29052013
TI  - The effect of early developmental problems in infancy: perspectives and clinical
      implications.

PMID- 29052012
TI  - Effect of nasal antihistamine on secretory IgA in nasal lavage of rats.
AB  - The humoral IgA is an immunoglobulin which plays a defensive role for organisms
      on mucosal surfaces. Today, intranasal antihistamines are effectively used in the
      treatment of allergic rhinitis. In our study, the effect of azelastine
      hydrochloride-a nasal antihistaminic-on humoral IgA of the nasal mucosa has been
      reviewed empirically. Twenty-four female Sprague-Dawley rats were included in our
      study. The rats were divided into three groups randomly. Group 1(azelastine
      hydrochloride): rats in this group had nasal azelastine hydrochloride (0.05%)
      applied for 30 days at 10 ul/nostril dosage. Group 2 (saline): saline (0.09%) was
      applied to the rats in this group for 30 days at 10 ul/nostril dosage. Group 3
      (control): no application was made throughout the study. The chemicals applied in
      Groups 1 and 2 were applied to both nostrils by mounting a flexible micropipette
      to the end of an insulin injector. At the beginning of the study, nasal lavage
      was performed to both nostrils of the rats in every group on the 15th and 30th
      day to aspirate irrigation solution (distilled water). The aspirated liquids were
      kept at - 80 degrees  temperature and reviewed together at the end of study.
      Within-group comparisons: in Group 1 (azelastine hydrochloride), the humoral IgA
      value on the 15th day was significantly higher than the basal value (p = 0.037).
      There is a significant difference between humoral IgA value on the 30th day and
      humoral IgA value on the 15th day (p = 0.045). In Group 2 (saline), no
      significant difference is available between basal, 15th day and 30th day humoral
      IgA values (p = 0.265). In Group 3 (control), no significant difference is
      available between basal, 15th day and 30th day humoral IgA values (p = 0.374).
      Between-group comparison: there is no significant difference in between-group
      humoral IgA basal values (p = 0.714). On days 15 and 30, Humoral IgA value of
      Group 1 was significantly higher than that of Groups 2 and 3 (p = 0.013, p =
      0.024, respectively). According to the results we achieved in our study, nasal
      antihistaminic (azelastine hydrochloride) significantly increases the level of
      humoral IgA. Our study is the first one in the literature to reveal a relation
      between nasal antihistaminic and humoral IgA and there is a further need for
      clinical, randomized and prospective studies.

PMID- 29052014
TI  - Predictive validity of a service-setting-based measure to identify infancy mental
      health problems: a population-based cohort study.
AB  - Measures to identify infancy mental health problems are essential to guide
      interventions and reduce the risk of developmental psychopathology in early
      years. We investigated a new service-setting-based measure the Copenhagen Infant
      Mental Health Screening (CIMHS) within the general child health surveillance by
      community health nurses (CHN). The study population of 2973 infants was assessed
      by CIMHS at age 9-10 months. A subsample of 416 children was examined at age 11/2
      years, using parent interviews including the Child Behavior Checklist (CBCL 11/2
      5), Check List of Autism and Toddlers (CHAT), Infant-Toddler Symptom Checklist
      (ITSCL), and the Bayley Scales of Infant and Toddler Development (BSID) and
      observations of behavior, communication, and interaction. Child mental disorders
      were diagnosed according to ICD-10 and parent-child relationship disorders
      according to DC:0-3R. Statistical analyses included logistic regression analyses
      adjusted and weighted to adjust for sampling and bias. CIMHS problems of sleep,
      feeding and eating, emotions, attention, communication, and language were
      associated with an up to fivefold increased risk of child mental disorders across
      the diagnostic spectrum of ICD-10 diagnoses. Homo-type continuity was seen in
      problems of sleep and feeding and eating being associated with a threefold
      increased risk of disorders within the same area, OR 3.0 (95% CI 1.6-5.4) and OR
      2.7 (95% CI 1.7-4.2), respectively. The sensitivity at high CIMHS problem scores
      was 32% and specificity 86%. In summary, CIMHS identify a broad range of infants'
      mental health problems that are amenable to guide intervention within the general
      child health surveillance.

PMID- 29052015
TI  - Stoichiometry and kinetics of single and mixed substrate uptake in Aspergillus
      niger.
AB  - In its natural environment, the filamentous fungus Aspergillus niger grows on
      decaying fruits and plant material, thereby enzymatically degrading the
      lignocellulosic constituents (lignin, cellulose, hemicellulose, and pectin) into
      a mixture of mono- and oligosaccharides. To investigate the kinetics and
      stoichiometry of growth of this fungus on lignocellulosic sugars, we carried out
      batch cultivations on six representative monosaccharides (glucose, xylose,
      mannose, rhamnose, arabinose, and galacturonic acid) and a mixture of these.
      Growth on these substrates was characterized in terms of biomass yields,
      oxygen/biomass ratios, and specific conversion rates. Interestingly, in
      combination, some of the carbon sources were consumed simultaneously and some
      sequentially. With a previously developed protocol, a sequential chemostat
      cultivation experiment was performed on a feed mixture of the six substrates. We
      found that the uptake of glucose, xylose, and mannose could be described with a
      Michaelis-Menten-type kinetics; however, these carbon sources seem to be
      competing for the same transport systems, while the uptake of arabinose,
      galacturonic acid, and rhamnose appeared to be repressed by the presence of other
      substrates.

PMID- 29052016
TI  - Prediction of vaginal birth after one ceasarean delivery for non-progressive
      labor.
AB  - PURPOSE: A model exists that predicts the probability of vaginal birth after
      cesarean (VBAC). That model is not stratified by indication at first cesarean.
      The aim of the study was to identify factors that may predict successful VBAC in
      patients operated for arrest of dilatation or descent at their first cesarean.
      METHODS: Retrospective analysis of all women with trials of labor after one
      cesarean (TOLAC) for non-progressive labor between November 2008 and October 2015
      was performed (n = 231). A multivariate logistic regression analysis was carried
      out to generate a prediction model for VBAC at hospital admission for planned
      TOLAC. RESULTS: During the study period, we had 231 parturient women who chose to
      undergo TOLAC following one previous cesarean delivery for non-progressive labor.
      Successful VBAC occurred in 155 (67.0%) parturient women. A model consisting of
      previous successful VBAC, lower head station on decision at previous cesarean
      delivery, lower newborn weight at previous cesarean delivery and larger cervical
      effacement on admission at delivery planned for TOLAC correctly classified 75.3%
      of cases (R 2 = 0.324, AUC 0.80, 95% CI 0.70-0.89, p < 0.001). CONCLUSION: A
      predictive model, which incorporates four variables available at hospital
      admission for the planned TOLAC, has been developed that allows the determination
      of likelihood of successful VBAC following one cesarean delivery for non
      progressive labor.

PMID- 29052017
TI  - Fertility after uterine artery embolization of fibroids: a systematic review.
AB  - PURPOSE: The impact of uterine artery embolization (UAE) for the purpose of
      diminishing the effect of uterine fibroids on fertility is unclear. We have
      investigated the reported rates of pregnancy and miscarriage after treatment of
      uterine fibroids with UAE. MATERIALS AND METHODS: We searched for relevant
      information in PubMed and Embase for randomized controlled trials (RCT),
      controlled clinical trials, comparative before-after trials, cohort studies, case
      control studies and case series where UAE treatment of premenopausal women was
      performed for uterine fibroids with and where a control intervention was
      included. The PRISMA guideline was used to do a systematic review using the main
      outcomes pregnancy rate and miscarriage rate. Risk of bias was assessed by the
      Cochrane risk of bias tool or by ROBINS-I. The quality of evidence was assessed
      by the GRADE approach. RESULTS: We included 17 studies (989 patients): 1 RCT, 2
      cohort studies, and 14 case series. Pregnancy rates after UAE were 50% in the RCT
      and 51 and 69% in the cohort studies. Among the case series median pregnancy rate
      was 29%. Miscarriage rates were 64% in the RCT. Miscarriage rates at 56 and 34%
      were found in the cohort studies after UAE. The median miscarriage rate was 25%
      in the case series. CONCLUSION: Pregnancy rate was found to be lower and
      miscarriage rate higher after UAE than after myomectomy. However, we found very
      low quality of evidence regarding the assessed outcomes and the reported
      proportions are uncertain. There is a need for improved prospective randomized
      studies to improve the evidence base. Systematic review registration number:
      CRD42016036661.

PMID- 29052018
TI  - End-Users' Product Preference Across Three Multipurpose Prevention Technology
      Delivery Forms: Baseline Results from Young Women in Kenya and South Africa.
AB  - A multipurpose prevention technology (MPT) that combines HIV and pregnancy
      prevention is a promising women's health intervention, particularly for young
      women. However, little is known about the drivers of acceptability and product
      choice for MPTs in this population. This paper explores approval ratings and
      stated choice across three different MPT delivery forms among potential end
      users. The Trio Study was a mixed-methods study in women ages 18-30 that examined
      acceptability of three MPT delivery forms: oral tablets, injections, and vaginal
      ring. Approval ratings and stated choice among the products was collected at
      baseline. Factors influencing stated product choice were explored using
      multivariable multinomial logistic regression. The majority (62%) of women in
      Trio stated they would choose injections, 27% would choose tablets and 11% would
      choose the ring. Significant predictors of choice included past experience with
      similar contraceptive delivery forms, age, and citing frequency of use as
      important. Ring choice was higher for older (25-30) women than for younger (18
      24) women (aRR = 3.1; p < 0.05). These results highlight the importance of
      familiarity in MPT product choice of potential for variations in MPT preference
      by age.

PMID- 29052020
TI  - Erratum to: A Rapid and Reliable Method for Total Protein Extraction from
      Succulent Plants for Proteomic Analysis.
AB  - The original version of this article unfortunately contains a mistake. The
      authors have inadvertently incorrectly listed the concentration of TCA in the
      acetone/TCA/beta-ME solution in the materials and methods section of this paper.
      The TCA concentration in Sects. 2.3.2 and 2.3.5 should be 10% TCA, making the
      solution acetone/10% TCA/0.07% beta-ME. It is now corrected with this erratum.

PMID- 29052021
TI  - A New Approach to Predict user Mobility Using Semantic Analysis and Machine
      Learning.
AB  - Mobility prediction is a technique in which the future location of a user is
      identified in a given network. Mobility prediction provides solutions to many day
      to-day life problems. It helps in seamless handovers in wireless networks to
      provide better location based services and to recalculate paths in Mobile Ad hoc
      Networks (MANET). In the present study, a framework is presented which predicts
      user mobility in presence and absence of mobility history. Naive Bayesian
      classification algorithm and Markov Model are used to predict user future
      location when user mobility history is available. An attempt is made to predict
      user future location by using Short Message Service (SMS) and instantaneous
      Geological coordinates in the absence of mobility patterns. The proposed
      technique compares the performance metrics with commonly used Markov Chain model.
      From the experimental results it is evident that the techniques used in this work
      gives better results when considering both spatial and temporal information. The
      proposed method predicts user's future location in the absence of mobility
      history quite fairly. The proposed work is applied to predict the mobility of
      medical rescue vehicles and social security systems.

PMID- 29052019
TI  - Image quality improvements using adaptive statistical iterative reconstruction
      for evaluating chronic myocardial infarction using iodine density images with
      spectral CT.
AB  - Single-source dual-energy CT (ssDECT) allows the reconstruction of iodine density
      images (IDIs) from projection based computing. We hypothesized that adding
      adaptive statistical iterative reconstruction (ASiR) could improve image quality.
      The aim of our study was to evaluate the effect and determine the optimal blend
      percentages of ASiR for IDI of myocardial late iodine enhancement (LIE) in the
      evaluation of chronic myocardial infarction using ssDECT. A total of 28 patients
      underwent cardiac LIE using a ssDECT scanner. IDIs between 0 and 100% of ASiR
      contributions in 10% increments were reconstructed. The signal-to-noise ratio
      (SNR) of remote myocardia and the contrast-to-noise ratio (CNR) of infarcted
      myocardia were measured. Transmural extent of infarction was graded using a 5
      point scale. The SNR, CNR, and transmural extent were assessed for each ASiR
      contribution ratio. The transmural extents were compared with MRI as a reference
      standard. Compared to 0% ASiR, the use of 20-100% ASiR resulted in a reduction of
      image noise (p < 0.01) without significant differences in the signal. Compared
      with 0% ASiR images, reconstruction with 100% ASiR image showed the highest
      improvement in SNR (229%; p < 0.001) and CNR (199%; p < 0.001). ASiR above 80%
      showed the highest ratio (73.7%) of accurate transmural extent classification. In
      conclusion, ASiR intensity of 80-100% in IDIs can improve image quality without
      changes in signal and maximizes the accuracy of transmural extent in infarcted
      myocardium.

PMID- 29052022
TI  - UDP-arabinopyranose mutase gene expressions are required for the biosynthesis of
      the arabinose side chain of both pectin and arabinoxyloglucan, and normal leaf
      expansion in Nicotiana tabacum.
AB  - Plant cell walls are composed of polysaccharides such as cellulose,
      hemicelluloses, and pectins, whose location and function differ depending on
      plant type. Arabinose is a constituent of many different cell wall components,
      including pectic rhamnogalacturonan I (RG-I) and II (RG-II),
      glucuronoarabinoxylans (GAX), and arabinoxyloglucan (AXG). Arabinose is found
      predominantly in the furanose rather than in the thermodynamically more stable
      pyranose form. The UDP-arabinopyranose mutases (UAMs) have been demonstrated to
      convert UDP-arabinopyranose (UDP-Arap) to UDP-arabinofuranose (UDP-Araf) in rice
      (Oryza sativa L.). The UAMs have been implicated in polysaccharide biosynthesis
      and developmental processes. Arabinose residues could be a component of many
      polysaccharides, including branched (1->5)-alpha-arabinans, arabinogalactans in
      pectic polysaccharides, and arabinoxyloglucans, which are abundant in the cell
      walls of solanaceous plants. Therefore, to elucidate the role of UAMs and
      arabinan side chains, we analyzed the UAM RNA interference transformants in
      tobacco (Nicotiana tabacum L.). The tobacco UAM gene family consists of four
      members. We generated RNAi transformants (NtUAM-KD) to down-regulate all four of
      the UAM members. The NtUAM-KD showed abnormal leaf development in the form of a
      callus-like structure and many holes in the leaf epidermis. A clear reduction in
      the pectic arabinan content was observed in the tissue of the NtUAM-KD leaf. The
      arabinose/xylose ratio in the xyloglucan-rich cell wall fraction was drastically
      reduced in NtUAM-KD. These results suggest that UAMs are required for Ara side
      chain biosynthesis in both RG-I and AXG in Solanaceae plants, and that arabinan
      mediated cell wall networks might be important for normal leaf expansion.

PMID- 29052023
TI  - The serum level and significance of lysyl oxidase-like 2 in patients with
      rheumatoid arthritis-associated interstitial lung disease.
AB  - Our previous experiments found that lysyl oxidase-like 2 (LOXL2) may be a useful
      preclinical serological marker for pulmonary fibrosis in the mouse model. The
      role of LOXL2 in rheumatoid arthritis-associated interstitial lung disease (RA
      ILD) is still unclear. We investigated whether serum LOXL2 levels are associated
      with RA-ILD patients. The levels of serum LOXL2 were measured by enzyme-linked
      immunosorbent assay in 49 RA-ILD patients (21 patients with ILD disease duration
      < 3 months; 28 patients with ILD disease duration > 3 months), 43 RA patients
      without ILD and 20 normal healthy controls. We assessed the correlations between
      the serum LOXL2 levels and clinical variables. Serum LOXL2 levels were
      significantly higher in RA patients than in normal healthy controls (326.79 +/-
      192.56 vs. 53.27 +/- 35.86 pg/ml, P < 0.01). No significant difference was
      present between the RA-ILD group and RA without ILD group (298.87 +/- 219.85 vs.
      358.60 +/- 152.16 pg/ml, P = 0.13). Notably, the serum LOXL2 levels were
      significantly higher in patients with ILD disease duration < 3 months than in
      those with ILD disease duration > 3 months (462.71 +/- 208.97 vs. 175.99 +/-
      130.55 pg/ml, P < 0.01) or without ILD (462.71 +/- 208.97 vs. 358.60 +/- 152.16
      pg/ml, P = 0.03). The serum LOXL2 levels in RA-ILD patients significantly
      correlated with DAS28 (rs = 0.31, P = 0.034), C-reactive protein (rs = 0.41, P =
      0.004), rheumatoid factor (rs = 0.41, P = 0.003), forced vital capacity (rs = -
      0.39, P = 0.02), and diffusion capacity of the lung for carbon monoxide (rs = -
      0.44, P = 0.009). LOXL2 may be involved in the pathogenesis of rheumatoid
      arthritis-associated interstitial lung disease and might be helpful in early
      diagnosis of RA-ILD.

PMID- 29052024
TI  - Multimodality imaging in secondary postpartum or postabortion hemorrhage:
      retained products of conception and related conditions.
AB  - Secondary postpartum hemorrhage (PPH) and postabortion hemorrhage are rare
      complications. Retained products of conception (RPOC) is among the most common
      causes of both secondary PPH and postabortion hemorrhage. Other less common
      causes of secondary PPH are uterine vascular abnormalities such as arteriovenous
      malformations and pseudoaneurysms. These are usually related to a history of a
      procedure such as dilation and curettage or cesarean delivery. Subinvolution of
      the placental site is an idiopathic cause of secondary PPH; this condition may be
      underrecognized and therefore could have a higher incidence than currently
      reported. Gestational trophoblastic disease is rare but commonly presents as
      secondary PPH and resembles RPOC in radiologic appearance. The first-line imaging
      modality for secondary PPH is ultrasound, but computed tomography and magnetic
      resonance imaging may be used if the ultrasound findings are indeterminate.
      Angiography is an important tool for the definitive diagnosis of uterine vascular
      abnormalities. Appropriate management requires radiologists to be familiar with
      the multimodality imaging features of secondary PPH or postabortion hemorrhage.

PMID- 29052025
TI  - Ultra-low-dose CT coronary angiography using 128-slice dual source CT with low
      concentration contrast agent: initial experience.
AB  - PURPOSE: To optimize and evaluate an ultra-low-dose (ULD) technique for CT
      coronary angiography (CTCA). MATERIALS AND METHODS: Eighty-two patients were
      randomly divided into two groups. ULD and routine CTCA were performed in groups A
      and B. Image quality, radiation dose and contrast agent were evaluated. RESULTS:
      The effective dose (ED) was 0.20 +/- 0.01 mSv for the ULD technique, a decrease
      of 87% (t = - 21.182, P < 0.001) compared with the control group. The total
      iodine content was 8.10 +/- 0 g, a decrease of 62% (t = - 73.458, P < 0.001)
      compared with 21.10 +/- 1.15 g for the control group. The assessment rates for
      both groups were the same (99.26 vs 99.64%, chi 2  = 0.727, P = 0.394). The
      contrast-to-noise ratio was 19.31 +/- 7.95 for group A and 20.73 +/- 5.07 for
      group B: the difference was not statistically significant (t = - 1.678, P =
      0.095). CONCLUSION: Using an ultra-low radiation dose and contrast agent
      technique, while maintaining an assessable image and improving the safety of the
      medical examination, was a feasible and reliable method for CTCA.

PMID- 29052026
TI  - High-dose chemotherapy and autologous peripheral blood stem cell transplantation
      with BCVAC regimen followed by maintenance chemotherapy for children with very
      high risk acute lymphoblastic leukemia.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the recommended
      treatment for children with very high risk acute lymphoblastic leukemia (ALL),
      but it requires adequate institutional infrastructure, experience, and expertise,
      especially for alternative donor HSCT. We review our experience with high-dose
      chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation
      (APBSCT), followed by post-APBSCT maintenance chemotherapy for children with very
      high risk ALL. Between August 1997 and November 2012, our institute was not
      successful with HLA-haploidentical HSCT. Thus, if patients lacked HLA-matched
      allogeneic donors or cord blood donors, we treated them with HDCT and APBSCT with
      carmustine, etoposide, cytarabine, and cyclophosphamide, followed by post-APBSCT
      maintenance chemotherapy with vincristine, oral prednisolone, methotrexate, and 6
      mercaptopurine.Ten patients underwent HDCT and APBSCT due to relapse, biphenotype
      leukemia, Philadelphia translocation, MLL rearrangement, hypodiploidy, and
      initial white blood cell count above 20.0 * 109/L. At a median 7.4 years from
      HDCT to APBSCT, overall survival (OS) was 70.0% +/- 14.5% and event-free survival
      (EFS) was 70.0% +/- 14.5%. Adverse events were tolerable, without treatment
      related mortality.This historical analysis may be a useful reference when
      allogeneic HSCT including alternative donor HSCT cannot be performed for children
      with very high risk ALL.

PMID- 29052028
TI  - In recognition of Ireland's contemporary medical scientists-Ted Dinan, Timothy
      O'Brien, Michael Hutchinson, Desmond FitzGerald, Michael Gibney, Mary Cannon and
      Fergal O'Gara.

PMID- 29052027
TI  - Four new diterpenoid alkaloids from Aconitum japonicum subsp. subcuneatum.
AB  - Diterpenoid alkaloids with remarkable chemical properties and biological
      activities are frequently found in plants of the genera Aconitum, Delphinium, and
      Garrya. Accordingly, several diterpenoid alkaloid constituents of Aconitum and
      Delphinium plants as well as their derivatives exhibited cytotoxic activity
      against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal
      cancer cell lines. Four new C19-diterpenoid alkaloids, 14-anisoyllasianine (1),
      14-anisoyl-N-deethylaconine (2), N-deethylaljesaconitine A (3), and N
      deethylnevadensine (4), together with 17 known C19- and C20-diterpenoid
      alkaloids, were isolated in a phytochemical investigation of rhizoma of Aconitum
      japonicum THUNB. subsp. subcuneatum (NAKAI) KADOTA. Their structures were
      elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and
      MS (HRMS). Eight known diterpenoid alkaloids, lipoaconitine, lipomesaconitine,
      aconine, nevadenine, talatisamine, nevadensine, ryosenamine, and
      dehydrolucidusculine, were isolated the first time from A. japonicum subsp.
      subcuneatum. Three of the new C19-diterpenoid alkaloids (1, 3, 4) and six of the
      known diterpenoid alkaloids were evaluated for cytotoxic activity against five
      human tumor cell lines.

PMID- 29052029
TI  - Migration and invasion induced by linoleic acid are mediated through fascin in
      MDA-MB-231 breast cancer cells.
AB  - Epidemiological studies strongly suggest an association between high levels of
      dietary fat intake and an increased risk of developing breast cancer. Linoleic
      acid (LA) is an essential omega-6 PUFA and the major fatty acid in occidental
      diets. In breast cancer cells, LA induces expression of plasminogen activator
      inhibitor-1, proliferation, migration, and invasion. Fascin is an actin
      crosslinker globular protein that generates actin bundles made of parallel actin
      filaments, which mediate formation and stability of microspikes, stress fibers,
      membrane ruffles, and filopodia. However, the role of fascin in migration and
      invasion induced by LA in MDA-MB-231 breast cancer cells remains to be studied.
      We demonstrate here that LA induces an increase of fascin expression in MDA-MB
      231 and MCF12A mammary epithelial cells. Particularly, LA induces the formation
      of filopodia and lamellipodia and the localization of fascin in these actin
      structures in MDA-MB-231 breast cancer cells. However, LA only induces formation
      of microspikes and the localization of fascin in these actin structures in
      mammary non-tumorigenic epithelial cells MCF12A. In addition, LA induces
      migration, invasion, and matrix metalloproteinase-9 secretion through a fascin
      dependent pathway in MDA-MB-231 cells. In summary, our findings demonstrate that
      fascin is required for migration and invasion induced by LA in MDA-MB-231 breast
      cancer cells.

PMID- 29052030
TI  - Validation of a Chinese version of the stress overload scale-short and its use as
      a screening tool for mental health status.
AB  - PURPOSE: Although stress emerges when environmental demands exceed personal
      resources, existing measurement methods for stress focus only on one aspect. The
      newly-developed Short Stress Overload Scale (SOS-S) assesses the extent of stress
      by assessing both event load (i.e., environmental demands) and personal
      vulnerability (i.e., personal resources). The present study was designed to
      evaluate the psychometric properties of the Chinese version of Stress Overload
      Scale-Short (SOS-SC), and further examine its roles in screening mental health
      status. METHODS: A total of 1364 participants were recruited from communities and
      colleges for scale validation. RESULTS: Reliabilities were good throughout the
      subsamples (omega > 0.80). Confirmatory factor analysis indicated the acceptable
      goodness-of-fit for the two-factor correlated model (Sample 1: 560 community
      residents). Multi-group confirmatory factor analysis confirmed measurement
      invariance across community residents (Sample 1) and college students (Sample 2
      and Sample 3). Criterion validity and convergent validity were established
      (Sample 2: 554 college students). Latent moderated structural equations
      demonstrated that the relationship between SOS-SC and depression is moderated by
      social support (Sample 2), further validating the SOS-SC. In addition, the SOS-SC
      effectively screened individuals in a population at different levels of mental
      health status (i.e., "at risk" vs. "at low risk" for depression symptoms and/or
      wellbeing). CONCLUSION: The SOS-SC exhibits acceptable psychometric properties in
      the Chinese context. That said, the two aspects of stress can be differentiated
      by the Chinese context, therefore, the SOS-SC can be used to measure stress and
      screen mental health status among the Chinese population, and monitor and
      evaluate health-promoting interventions.

PMID- 29052031
TI  - Do Pharmaceuticals Improve Driving in Individuals with ADHD? A Review of the
      Literature and Evidence for Clinical Practice.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is defined as a disorder of
      impaired attention and/or behavioral control. Studies suggest that the condition
      can dispose individuals to a higher risk of automobile accidents. ADHD symptoms
      respond to pharmacotherapy in a majority of uncomplicated cases. Evidence on how
      pharmacotherapies for ADHD impact driving behavior or outcomes could allow
      clinicians to support on-road safety rationally. We therefore undertook a review
      to identify the evidence base to date indicating positive or negative effects of
      pharmacotherapies on driving behavior in individuals with ADHD. Further, we
      evaluated the level of evidence for these effects, their specificity to ADHD, and
      how they may inform clinical care. We identified studies involving
      pharmacotherapy for ADHD that evaluated driving-related activities or outcomes.
      We then categorized these studies by the mode of measurement used and by the ADHD
      specificity of the driving behaviors measured. Finally, we extracted themes of
      interest to clinical practice in pharmacologic intervention. In total, 14
      studies, involving 2-61 subjects diagnosed with ADHD, looked at computer
      measured, observer-measured, or self-reported driving behavior correlates of
      pharmacotherapy during simulation or on-road driving. Of these studies, 13
      involved psychostimulant agents and two used atomoxetine. All but three
      investigations (one of methylphenidate, one of mixed amphetamine salts, and one
      of atomoxetine) found favorable changes in measures such as steering and braking
      behaviors or reaction to unexpected events. One study found adverse effects on
      driving at hour 17 following mixed amphetamine salt administration. Four studies
      compared two pharmacotherapies, and each found differences in measured driving
      behavior between the therapies. One study explored impact on ADHD-specific
      driving impairments, and the same study was the only one to explore correlation
      of clinical measures (ADHD symptoms and self-reported driving behavior) with
      medication-associated changes-finding dissociation between changes in ADHD
      symptoms and changes in measured driving measures. While data to date are limited
      on the ADHD-specific effects of pharmacotherapies used for ADHD on driving, it is
      clear from our review that these agents have effects on driving-relevant
      behaviors. Further research is urgently needed to develop an evidence base for
      clinically predictable effects of pharmacotherapy on driving safety in
      individuals with ADHD. If possible, clinicians should evaluate the positive and
      negative effects of pharmacotherapy on driving in their clients.

PMID- 29052032
TI  - Co-production of MCR-1 and extended-spectrum beta-lactamase in Escherichia coli
      recovered from urinary tract infections in Switzerland.

PMID- 29052033
TI  - A random-perturbation therapy in chronic non-specific low-back pain patients: a
      randomised controlled trial.
AB  - The purpose of the study was to assess the effectiveness of a specific
      rehabilitation therapy for chronic non-specific low-back pain patients, based on
      a random/irregular functional perturbation training induced by force disturbances
      to the spine. Forty patients (20 controls and 20 in the perturbation-based group)
      finished the whole experimental design. A random-perturbation exercise, which
      included variable and unpredictable disturbances, was implemented in the therapy
      of the perturbation-based group (13 weeks, two times per week and 1.5 h per
      session). The participants of the control group did not receive any specific
      training. Low-back pain, muscle strength, and neuromuscular control of spine
      stability were investigated before and after the therapy using the visual analog
      scale, maximal isometric and isokinetic contractions, nonlinear time series
      analysis, and by determining the stiffness and damping of the trunk after sudden
      perturbations. The perturbation-based therapy reduced patient's low-back pain
      (35%), increased muscle strength (15-22%), and trunk stiffness (13%), while no
      significant changes were observed in the control group. It can be concluded that
      the proposed therapy has the potential to enhance trunk muscle capability as well
      as sensory information processing within the motor system during sudden loading
      and, as a consequence, improve the stabilization of the trunk.

PMID- 29052034
TI  - High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly
      Japanese volunteers: a 5-year prospective observational study.
AB  - BACKGROUND: Serum adiponectin levels are associated with frailty and
      cardiovascular diseases. Longitudinal changes in adiponectin levels might enhance
      our understanding of age-related conditions and diseases. AIMS: This prospective
      observational study aimed to: (1) elucidate age-related changes in high-molecular
      weight (HMW) adiponectin levels; and (2) identify variables predictive of
      elevated HMW adiponectin levels and the association with well-known adiponectin
      single-nucleotide polymorphisms (SNPs) in healthy, elderly Japanese participants.
      METHODS: Healthy elderly volunteers (n = 196; 55 men and 141 women; median age
      72.0 years; range 69.0-75.0 years) underwent anthropometric and physical function
      measurements, as well as laboratory tests at baseline and the 5-year follow-up.
      RESULTS: HMW adiponectin levels were significantly higher in women than in men
      (8.4, 5.3-11.9 vs. 5.7, 3.1-9.0 MUg/mL; p < 0.001) at baseline and decreased
      significantly at follow-up in women (7.7, 4.8-11.2 MUg/mL; p < 0.001), but not in
      men. In the multiple regression analysis, high-density lipoprotein cholesterol
      levels and body weight were independent predictors of HMW adiponectin levels. The
      rate of change in HMW adiponectin levels was inversely correlated with the rates
      of change in body weight, body mass index, and knee leg extension strengths, and
      positively correlated with rates of change in high-density lipoprotein
      cholesterol and one-leg standing time. There were no significant differences in
      HMW adiponectin levels among SNPs. DISCUSSION: Decreasing HMW adiponectin levels
      might lead to an increased risk of cardiovascular diseases in elderly women.
      CONCLUSION: HMW adiponectin levels significantly decreased over a 5-year period
      in community-dwelling elderly Japanese women.

PMID- 29052035
TI  - Why a surgically treated humeral shaft fracture became a nonunion: review of 11
      years in two trauma centers.
AB  - AIM: The aim of this study was to evaluate nonunion causes of surgically treated
      humeral shaft fractures in two different trauma centers. METHODS: A total of 327
      cases of humeral shaft fractures were treated in 11 years in two trauma centers.
      We retrospectively reviewed in detail some factors in order to understand the
      reasons for nonunion: (1) fracture type, according to the AO classification, (2)
      grade of open fracture, according to Gustilo-Anderson, (3) timing, (4) reduction
      and (5) fixation. RESULTS: We observed 19 nonunions, 10 women and 9 men, with an
      average age of 57 years. Fractures were 1 A1 case, 2 A2 cases, 4 B2 cases, 6 B3
      cases, 2 C1 cases, 1 C2 case and 3 C3 cases. Three cases had a simple fracture
      with two fragments; all the other were comminuted. Fifteen cases were closed,
      four open. The major criticalities observed were fracture comminution, exposure,
      unstable fixation and bone resorption. All 19 patients with nonunion underwent
      surgical fixation with compression plate and frozen cortical bone graft. A 4.5
      LCP plate was used in 17 cases. The remaining 2 cases had an anatomical site
      specific proximal humeral 3.5-mm LCP plate (Synthes, Paoli, PA, USA). In 17
      patients, the nonunion healed: 15 cases treated with a 4.5 straight plate, and 2
      cases with an anatomical site-specific proximal humeral 3.5 mm LCP plate, at a
      mean of 5 months. In 2 cases, consolidation was not reached. CONCLUSIONS: We
      believe that humeral diaphyseal fractures should be treated surgically to avoid
      many complications. Our retrospective analysis indicates that factors that lead
      to a fixation failure are fracture comminution, open fracture, unstable fixation.
      The 19 nonunions treated with compression plating and frozen bone graft
      demonstrated consolidation in almost 90% of the cases.

PMID- 29052036
TI  - Rapidly increasing incidence in scoliosis surgery over 14 years in a nationwide
      sample.
AB  - PURPOSE: Severe scoliosis is primarily managed with surgery. This cohort study
      describes the incidence of surgically treated scoliosis among Swedish youth and
      young adults, stratified by age, sex, scoliosis type, and surgical approach and
      identifies changes in incidence rate and hospital length of stay (LOS),
      infections requiring re-surgery and mortality within 90 days. METHODS: Swedish
      youth, 0-21 years, (n = 3062) with a diagnostic code for scoliosis and spine
      surgery between 2000 and 2013 were selected from the National Patient Register.
      Incidence was computed by comparing individuals with surgically treated scoliosis
      to the total at risk population. Linear regression models and Spearman
      correlation coefficients analyzed trends over time. RESULTS: Overall annual
      incidence per 100,000 individuals was 9.1 (5.9 males/12.5 females). Annual
      incidence increased over 14 years from 5.1 to 9.8; an average 4.6% per year (p <
      0.001). Adolescent idiopathic scoliosis was most common (4.5 per 100,000; n =
      1516) followed by neuromuscular 2.7 (n = 913) and congenital 0.7 (n = 236).
      Average LOS decreased among scoliosis types except infantile and neuromuscular
      scoliosis. Posterior fusion was the most common surgical approach (75%) followed
      by anterior (18%) and anteroposterior fusion (7%). Posterior fusions
      significantly increased with a resultant decrease in anterior and anteroposterior
      fusion over time. Individuals with neuromuscular scoliosis exhibited the highest
      mortality (n = 12; 1.3%) and (n = 59; 6%) of individuals with neuromuscular
      scoliosis and (n = 12; 15%) with scoliosis related to MMC required revision
      surgery due to post-op infection. CONCLUSIONS: Surgical management of scoliosis
      is increasing with a concurrent decrease in hospital LOS. Surgical management of
      neuromuscular scoliosis is associated with high 90-day post-operative infections
      and mortality rate.

PMID- 29052037
TI  - Effects of mirror placement on sagittal alignment of the spine during acquisition
      of full-spine standing X-Rays.
AB  - PURPOSE: The line of sight when whole-spine radiographs are taken has not been
      defined. In our 2012 health screening study (TOEI study), whole-spine radiographs
      were taken with the volunteers in the most relaxed position and with a horizontal
      gaze. However, in the TOEI 2014 study, a mirror was placed in front of their
      faces to unify their line of sight. To our knowledge, there are no reports on how
      the sagittal alignment changes when radiographs are taken using a mirror. The
      purpose of this study was to investigate how mirror placement impacted sagittal
      spinal alignment in whole-spine radiographs taken while standing. METHODS:
      Volunteers who participated in both the TOEI 2012 and 2014 studies were
      recruited. Pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK),
      cervical lordosis (CL), slope of McGregor's line (McGS), and C7 sagittal vertical
      axis (C7 SVA) were examined using software. RESULTS: Three hundred fifty-four
      volunteers (142 males, 212 females, average age in 2012: 72 years) whose
      radiographs were evaluated in both previous studies were enrolled. The average
      parameters of 2012 and 2014 were: PT: 18 degrees  and 21 degrees  (P < 0.01), LL:
      40 degrees  and 40 degrees , TK: 34 degrees  and 34 degrees , CL: 13 degrees  and
      23 degrees  (P < 0.01), McGS: 2 degrees  +/- 11 degrees  and - 9 degrees  +/- 8
      degrees  (P < 0.01), and C7 SVA: 46 and 23 mm (P < 0.01), respectively. In the
      Levene test, the McGS variation in 2014 [95% confidence interval (CI) 0.9-3.4]
      was significantly smaller than that in 2012 (95% CI - 9.7 to - 8.0, P < 0.01).
      CONCLUSION: The smaller McGS variation in the TOEI 2014 study suggested that
      mirror placement could standardize the head's position. These results showed that
      the mirror placement retroflexed cervical alignment and caused the head to lean
      backward. It is important that a mirror is placed to unify the line of sight.

PMID- 29052038
TI  - Proof of Concept Coded Aperture Miniature Mass Spectrometer Using a Cycloidal
      Sector Mass Analyzer, a Carbon Nanotube (CNT) Field Emission Electron Ionization
      Source, and an Array Detector.
AB  - Despite many potential applications, miniature mass spectrometers have had
      limited adoption in the field due to the tradeoff between throughput and
      resolution that limits their performance relative to laboratory instruments.
      Recently, a solution to this tradeoff has been demonstrated by using spatially
      coded apertures in magnetic sector mass spectrometers, enabling throughput and
      signal-to-background improvements of greater than an order of magnitude with no
      loss of resolution. This paper describes a proof of concept demonstration of a
      cycloidal coded aperture miniature mass spectrometer (C-CAMMS) demonstrating use
      of spatially coded apertures in a cycloidal sector mass analyzer for the first
      time. C-CAMMS also incorporates a miniature carbon nanotube (CNT) field emission
      electron ionization source and a capacitive transimpedance amplifier (CTIA) ion
      array detector. Results confirm the cycloidal mass analyzer's compatibility with
      aperture coding. A >10* increase in throughput was achieved without loss of
      resolution compared with a single slit instrument. Several areas where additional
      improvement can be realized are identified. Graphical Abstract ?.

PMID- 29052039
TI  - Qualitative evaluation of mobile cancer apps with particular attention to the
      target group, content, and advertising.
AB  - PURPOSE: Medical apps are gaining importance rapidly. Also in the field of cancer
      care, apps are offered. Yet, so far little is known with respect to their
      quality. METHODS: In a pilot phase we developed a rating tool based on formal and
      content-related criteria for the assessment of cancer apps. We used this
      instrument on cancer apps available in the App Store (iOS) concerning breast,
      prostate and colorectal cancer. The results were stratified according to target
      group, content and advertising. RESULTS: We assessed 41 mobile cancer apps. Six
      apps (14.63%) scored very high, fifteen apps (36.59%) high, seventeen apps
      (41.46%) were deficient, and three apps (7.32%) were insufficient. The largest
      group of apps represents those apps with the "deficient" rating. The very good to
      good apps had reliable sources, a concrete intent/ purpose in their app
      description, and a strict distinction of scientific content and advertisement.
      Apps with the predicates "deficient" or "insufficient" had particularly poor
      ratings, e.g. in the subscales "information on sources" and "data protection".
      CONCLUSIONS: Almost half of the tested apps were deficient or insufficient. In
      order to improve safety of patients using apps, some regulation seems mandatory.
      Putting apps under the legislation for medical products might be one way to
      better regulate and control quality. Second, efforts should focus on the
      development of checklists that make it easier for patients to search for suitable
      cancer apps.

PMID- 29052040
TI  - Histological criteria for age determination of fatal venous thromboembolism.
AB  - In clinical and forensic practice, fatal thromboembolism is a major problem,
      particularly in a patient with no pre-existing risk factors. Out of a recent
      case, we discuss here the criteria for age determination of venous thrombi in a
      46-year-old female with concomitant deep vein thrombosis in the common femoral
      left vein and in the right heart and fatal pulmonary embolism. At autopsy,
      histopathology and immunohistochemistry evidenced the different composition of
      thrombi in different sites and permitted to define the different timing. We
      discuss and review the histopathological criteria for age estimation of venous
      thrombi starting from the case and in relation to the acquired and inherited
      thrombophilic risk factors. The appropriateness of clinical management is also
      discussed.

PMID- 29052041
TI  - Suicide of isolated inmates suffering from psychiatric disorders: when a
      preventive measure becomes punitive.
AB  - We performed external autopsies and examinations on two inmates who had committed
      suicide by hanging themselves with their underwear and using the window bars of
      their cells as ligature points after they had been placed in solitary
      confinement. In one case, the inmate had even been deprived of her clothing (with
      the exception to her underwear). Underwear has been rarely described as a means
      for self-harm and, to the best of our knowledge, no previous study has focused on
      cases of prison suicides committed using this garment, even though it is
      available to every inmate. The two cases were very similar; both inmates were
      young, physically aggressive and in their first week at a new facility; both had
      been affected by mental disorders, had been prescribed psychotropic medications
      and had histories of psychiatric hospitalisation. In each case, the psychiatric
      evaluations had highlighted significant suicidal risk. We discuss these two cases
      in an attempt to describe the complexity of and contradictions within the
      management of suicidal inmates at correctional facilities. We aim to propose new
      strategies and emphasise the need to introduce evidence-based standardised
      protocols over inhumane, ineffective and simplistic punitive measures in the
      management of these individuals.

PMID- 29052042
TI  - Paternal lineage affinity of the Malay subethnic and Orang Asli populations in
      Peninsular Malaysia.
AB  - Peninsular Malaysia is populated by the Malays, Chinese, Indians, and Orang Asli.
      We have analyzed 17 Y-STRs loci for 243 randomly unrelated individuals, which
      include 153 Malays (7 Acheh, 13 Champa, 11 Rawa, 9 Kedah, 23 Minang, 15 Bugis, 43
      Kelantan, 14 Jawa, and 18 Bugis) and 90 Orang Asli [54 Semang (16 Kensiu, 13
      Lanoh, 25 Bateq); 30 Senoi (21 Semai, 9 Che Wong); and 6 Proto-Malay (6 Orang
      Kanaq)] from selected settlements in Peninsular Malaysia using the AmpFlSTR
      YfilerTM kit (Applied BiosystemsTM). The overall haplotype diversity is 0.9966,
      i.e., 0.9984 for the Malays and 0.9793 for the Orang Asli. A total of 158
      haplotypes (65.02%) were individually unique. The p value and pairwise Rst
      analysis was calculated to show the genetic structure of the samples with other
      world populations (from YHRD website). Based on the Y-STR data, Champa, Acheh,
      Kedah, Minang, and Kelantan are clustered together. Lanoh and Kensiu (Semang) are
      very closely related, suggesting similar paternal ancestry. Jawa Malays and
      Indonesian Java, plus the Bugis Malays and Australian Aborigines shared high
      degree of paternal lineage affinity. This study presents data for very precious
      relict groups, who are the earliest inhabitants of Peninsular Malaysia.

PMID- 29052043
TI  - Biodegradation and chemotaxis of polychlorinated biphenyls, biphenyls, and their
      metabolites by Rhodococcus spp.
AB  - Two biphenyl-degrading bacterial strains, SS1 and SS2, were isolated from
      polychlorinated biphenyl (PCB)-contaminated soil. They were identified as
      Rhodococcus ruber and Rhodococcus pyridinivorans based on the 16S rRNA gene
      sequence, as well as morphological, physiological and biochemical
      characteristics. SS1 and SS2 exhibited tolerance to 2000 and 3000 mg/L of
      biphenyl. And they could degrade 83.2 and 71.5% of 1300 mg/L biphenyl within 84
      h, respectively. In the case of low-chlorinated PCB congeners, benzoate and 3
      chlorobenzoate, the degradation activities of SS1 and SS2 were also significant.
      In addition, these two strains exhibited chemotactic response toward TCA-cycle
      intermediates, benzoate, biphenyl and 2-chlorobenzoate. This study indicated
      that, like the flagellated bacteria, non-flagellated Rhodococcus spp. might
      actively seek substrates through the process of chemotaxis once the substrates
      are depleted in their surroundings. Together, these data provide supporting
      evidence that SS1 and SS2 might be good candidates for restoring biphenyl/PCB
      polluted environments.

PMID- 29052044
TI  - The cost-effectiveness of exercise-based cardiac rehabilitation: a systematic
      review of the characteristics and methodological quality of published literature.
AB  - AIM: This descriptive review aimed to assess the characteristics and
      methodological quality of economic evaluations of cardiac rehabilitation (CR)
      programs according to updated economic guidelines for healthcare interventions.
      Recommendations will be made to inform future research addressing the impact of a
      physical exercise component on cost-effectiveness. METHODS: Electronic databases
      were searched for economic evaluations of exercise-based CR programs published in
      English between 2000 and 2014. The Consolidated Health Economic Evaluation
      Reporting Standards (CHEERS) statement was used to review the methodological
      quality of included economic evaluations. RESULTS: Fifteen economic evaluations
      met the review inclusion criteria. Assessed study characteristics exhibited wide
      variability, particularly in their economic perspective, time horizon, setting,
      comparators and included costs, with significant heterogeneity in exercise dose
      across interventions. Ten evaluations were based on randomised controlled trials
      (RCTs) spanning 6-24 months but often with weak or inconclusive results; two were
      modelling studies; and the final three utilised longer time horizons of 3.5-5
      years from which findings suggest that long-term exercise-based CR results in
      lower costs, reduced hospitalisations and a longer cumulative patient lifetime.
      None of the 15 articles met all the CHEERS quality criteria, with the majority
      either fully or partially meeting a selection of the assessed variables.
      CONCLUSION: Evidence exists supporting the cost-effectiveness of exercise-based
      CR for cardiovascular disease patients. However, variability in CR program
      delivery and weak consistency between study perspective and design limits study
      comparability and therefore the accumulation of evidence in support of a
      particular exercise regime. The generalisability of study findings was limited
      due to the exclusion of patients with comorbidities as would typically be found
      in a real-world setting. The use of longer time-horizons would be more comparable
      with a chronic condition and enable economic assessments of the long-term effects
      of CR. As none of the articles met recent reporting standards for the economic
      assessment of healthcare interventions, it is recommended that future studies
      adhere to such guidelines.

PMID- 29052045
TI  - Hypothalamic dysfunction in heart failure: pathogenetic mechanisms and
      therapeutic implications.
AB  - Neurohumoral activation is an important feature of heart failure. Recent advances
      in molecular biology and imaging techniques permitted a better understanding of
      the central role that hypothalamus plays in the modulation of dysfunctional
      mechanisms, as well as the occurrence of comorbidities, such as depression, in
      heart failure patients. This review summarizes the commonly reported neural
      reflexes and molecular signaling pathways at the level of the hypothalamus along
      with the dysfunctional mechanisms within the paraventricular nucleus and other
      areas of the hypothalamus in heart failure and describes some relevant
      therapeutic implications.

PMID- 29052047
TI  - An alternative approach for estimating above ground biomass using Resourcesat-2
      satellite data and artificial neural network in Bundelkhand region of India.
AB  - Determination of above ground biomass (AGB) of any forest is a longstanding
      scientific endeavor, which helps to estimate net primary productivity, carbon
      stock and other biophysical parameters of that forest. With advancement of
      geospatial technology in last few decades, AGB estimation now can be done using
      space-borne and airborne remotely sensed data. It is a well-established, time
      saving and cost effective technique with high precision and is frequently applied
      by the scientific community. It involves development of allometric equations
      based on correlations of ground-based forest biomass measurements with vegetation
      indices derived from remotely sensed data. However, selection of the best-fit and
      explanatory models of biomass estimation often becomes a difficult proposition
      with respect to the image data resolution (spatial and spectral) as well as the
      sensor platform position in space. Using Resourcesat-2 satellite data and
      Normalized Difference Vegetation Index (NDVI), this pilot scale study compared
      traditional linear and nonlinear models with an artificial intelligence-based non
      parametric technique, i.e. artificial neural network (ANN) for formulation of the
      best-fit model to determine AGB of forest of the Bundelkhand region of India. The
      results confirmed the superiority of ANN over other models in terms of several
      statistical significance and reliability assessment measures. Accordingly, this
      study proposed the use of ANN instead of traditional models for determination of
      AGB and other bio-physical parameters of any dry deciduous forest of tropical sub
      humid or semi-arid area. In addition, large numbers of sampling sites with
      different quadrant sizes for trees, shrubs, and herbs as well as application of
      LiDAR data as predictor variable were recommended for very high precision
      modelling in ANN for a large scale study.

PMID- 29052048
TI  - The effect of divalent ions on L-alpha-phosphatidylcholine from egg yolk
      monolayers at the air/water interface.
AB  - The Langmuir monolayers of L-alpha-phosphatidylcholine from egg yolk were studied
      by Wilhelmy method. The surface pressure versus molecular area isotherm of lipid
      on pure water and different subphase (with a presence of divalent ions: Sr2+,
      Cd2+, Ba2+, Pb2+) was obtained. The limiting area of the isotherms depends on the
      presence of subphase ions. The addition of divalent ions to the subphase
      stabilized the monolayers and increased the limiting areas of the monolayer.
      During the compression in monolayer complexes of 1:1 and 2:1 stoichiometry
      between L-alpha-phosphatidylcholine from egg yolk and divalent ions are formed.
      We used the equilibrium theory to describe the behavior of monolayer components
      at the air/water interface. An equilibrium theory to describe the behavior of
      monolayer components at the air/water interface was developed in order to obtain
      the stability constants and area occupied by one molecule of LMe2+ or L2Me2+
      complexes, and complex formation energy (Gibbs free energy) values. These
      mathematically derived and experimentally confirmed values are of great
      importance for the interpretation of phenomena occurring in lipid monolayers and
      bilayers.

PMID- 29052046
TI  - Headache and pregnancy: a systematic review.
AB  - This systematic review summarizes the existing data on headache and pregnancy
      with a scope on clinical headache phenotypes, treatment of headaches in pregnancy
      and effects of headache medications on the child during pregnancy and
      breastfeeding, headache related complications, and diagnostics of headache in
      pregnancy. Headache during pregnancy can be both primary and secondary, and in
      the last case can be a symptom of a life-threatening condition. The most common
      secondary headaches are stroke, cerebral venous thrombosis, subarachnoid
      hemorrhage, pituitary tumor, choriocarcinoma, eclampsia, preeclampsia, idiopathic
      intracranial hypertension, and reversible cerebral vasoconstriction syndrome.
      Migraine is a risk factor for pregnancy complications, particularly vascular
      events. Data regarding other primary headache conditions are still scarce. Early
      diagnostics of the disease manifested by headache is important for mother and
      fetus life. It is especially important to identify "red flag symptoms" suggesting
      that headache is a symptom of a serious disease. In order to exclude a secondary
      headache additional studies can be necessary: electroencephalography, ultrasound
      of the vessels of the head and neck, brain MRI and MR angiography with contrast
      ophthalmoscopy and lumbar puncture. During pregnancy and breastfeeding the
      preferred therapeutic strategy for the treatment of primary headaches should
      always be a non-pharmacological one. Treatment should not be postponed as an
      undermanaged headache can lead to stress, sleep deprivation, depression and poor
      nutritional intake that in turn can have negative consequences for both mother
      and baby. Therefore, if non-pharmacological interventions seem inadequate, a well
      considered choice should be made concerning the use of medication, taking into
      account all the benefits and possible risks.

PMID- 29052049
TI  - Photophysicochemical, calf thymus DNA binding and in vitro photocytotoxicity
      properties of tetra-morpholinoethoxy-substituted phthalocyanines and their water
      soluble quaternized derivatives.
AB  - In this study, morpholinoethoxy-substituted metal-free (3), zinc(II) (4) and
      indium(III) (5) phthalocyanines were synthesized. These phthalocyanines were
      converted to their water-soluble quaternized derivatives (3Q-5Q) using excess
      methyl iodide as a quaternization agent. All these phthalocyanines (Pcs) were
      characterized by elemental analysis and different spectroscopic methods such as
      FT-IR, 1H NMR, UV-Vis and mass spectrometry. The photophysical and photochemical
      properties such as fluorescence and generation of singlet oxygen were
      investigated for determination of these phthalocyanines as photosensitizers in
      photodynamic therapy (PDT) applications. The binding properties of quaternized
      phthalocyanines (3Q-5Q) to calf thymus DNA (CT-DNA) were investigated by UV-Vis
      and fluorescence spectrophotometric methods. The quenching effect of all
      quaternized phthalocyanines on the fluorescence intensity of SYBR Green-DNA
      complex was determined. The mixtures of 3Q, 4Q or 5Q and DNA solutions were used
      to determine the change in T m of double helix DNA with thermal denaturation
      profile. In addition, thermodynamic parameters considering their aggregation in
      buffer solution, which shows the spontaneity of the reactions between DNA and
      quaternized Pcs were investigated. On the other hand, in vitro phototoxicity and
      cytotoxicity behavior of the quaternized water-soluble phthalocyanine
      photosensitizers (3Q-5Q) were tested against the cervical cancer cell line named
      HeLa for evaluation of their suitability for treatment of cancer by PDT method.
      Peripherally tetra-substituted neutral and quaternized metal-free and
      metallophthalocyanines (MPcs) (Zn, In) bearing morpholinoethoxy groups were
      prepared. The binding of quaternized compounds (3Q-5Q) to CT-DNA were examined
      using UV-Vis, fluorescence spectra, thermal denaturation profiles and K SV
      values. Besides, thermodynamic studies indicated that binding of 3Q-5Q to DNA was
      spontaneous. On the other hand, in vitro phototoxicity and cytotoxicity behavior
      of the quaternized water-soluble phthalocyanine photosensitizers (3Q-5Q) were
      tested against the cervical cancer cell line named HeLa for evaluation of their
      suitability for treatment of cancer by PDT method.

PMID- 29052050
TI  - Inter-rater Reliability of the Dysphagia Outcome and Severity Scale (DOSS):
      Effects of Clinical Experience, Audio-Recording and Training.
AB  - The Dysphagia Outcome and Severity Scale (DOSS) is widely used to measure
      dysphagia severity based on videofluoroscopy (VFSS). This study investigated
      inter-rater reliability (IRR) of the DOSS. It also determined the effect of
      clinical experience, VFSS audio-recording and training on DOSS IRR. A
      quantitative prospective research design was used. Seventeen speech and language
      pathologists (SLPs) were recruited from an acute teaching hospital, Dublin (> 3
      years' VFSS experience, n = 10) and from a postgraduate dysphagia programme in a
      university setting (< 3 years' VFSS experience; n = 7). During testing,
      participants viewed eight VFSS clips (5 with audio-recording). Each VFSS clip was
      independently rated using the DOSS scale. Four weeks later, the less experienced
      group attended a 1-h training session on DOSS rating after which DOSS IRR was re
      tested. Cohen's kappa co-efficient was used to establish IRR. IRR of the DOSS
      presented only fair agreement (kappa = 0.36, p < 0.05). DOSS IRR was
      significantly higher (kappa = 0.342) within the more experienced SLP group,
      compared to the less experienced SLP group (kappa = 0.298) (p < 0.05). DOSS IRR
      was significantly higher in VFSS clips with audio-recording (kappa = 0.287)
      compared to VFSS clips without audio-recording (kappa = - 0.0395) (p < 0.05). IRR
      of the DOSS pre-training (kappa = 0.328) was significantly better comparing to
      post-training (kappa = 0.218) (p < 0.05). Findings raise concerns as the DOSS is
      frequently used in clinical practice to capture dysphagia severity and to monitor
      changes.

PMID- 29052051
TI  - Tongue-Strengthening Exercises in Healthy Older Adults: Specificity of Bulb
      Position and Detraining Effects.
AB  - Clinical tongue-strengthening therapy programs are generally based on the
      principles of exercise and motor learning, including the specificity paradigm.
      The aim of this study was to investigate the specific effect of anterior and
      posterior tongue-strengthening exercises (TSE) on tongue strength (TS) in healthy
      older adults and to measure possible detraining effects. Sixteen healthy elderly
      completed 8 weeks of TSE by means of the Iowa Oral Performance Instrument (IOPI).
      They were distributed in two different treatment arms and performed either
      exclusively anterior or posterior TSE (ATSE, n = 9 or PTSE, n = 7) depending on
      the treatment arm. Anterior and posterior maximal isometric pressures (MIPA,
      MIPP) were measured at baseline, halfway, and after completion of the training
      sessions. Detraining was measured by repeating MIPA and MIPP measures 4 weeks
      after the last session of TSE. MIPA and MIPP increased significantly in both
      treatment arms. MIPA was significantly higher in the ATSE group compared to the
      PTSE group across all measures in time. No significant differences were observed
      in MIPP between the ATSE and PTSE groups. Regardless of treatment arm, there was
      no significant detraining effect measured 4 weeks after the last TSE session.
      This study suggests that TSE show partial specificity concerning bulb position.
      We conclude that especially anterior training results in higher anterior TS in
      comparison with posterior exercises. Furthermore, we found no detraining effects,
      independent of bulb location.

PMID- 29052052
TI  - Long-term outcomes of endoscopic submucosal dissection versus surgery in early
      gastric cancer meeting expanded indication including undifferentiated-type
      tumors: a criteria-based analysis.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC)
      meeting the expanded indication is considered investigational. We aimed to
      compare long-term outcomes of ESD and surgery for EGC in the expanded indication
      based on each criterion. METHODS: This study included 1823 consecutive EGC
      patients meeting expanded indication conditions and treated at a tertiary
      referral center: 916 and 907 patients underwent surgery or ESD, respectively. The
      expanded indication included four discrete criteria: (I) intramucosal
      differentiated tumor, without ulcers, size >2 cm; (II) intramucosal
      differentiated tumor, with ulcers, size <=3 cm; (III) intramucosal
      undifferentiated tumor, without ulcers, size <=2 cm; and (IV) submucosal invasion
      <500 MUm (sm1), differentiated tumor, size <=3 cm. We selected 522 patients in
      each group by propensity score matching and retrospectively evaluated each group.
      The primary outcome was overall survival (OS); the secondary outcomes were
      disease-specific survival (DSS), recurrence-free survival (RFS), and treatment
      related complications. RESULTS: In all patients and subgroups meeting each
      criterion, OS and DSS were not significantly different between groups (OS and
      DSS, all patients: p = 0.354 and p = 0.930; criteria I: p = 0.558 and p = 0.688;
      criterion II: p = 1.000 and p = 1.000; criterion III: p = 0.750 and p = 0.799;
      and criterion IV: p = 0.599 and p = 0.871). RFS, in all patients and criterion I,
      was significantly shorter in the ESD group than in the surgery group (p < 0.001
      and p < 0.003, respectively). The surgery group showed higher rates of late and
      severe treatment-related complications than the ESD group. CONCLUSIONS: ESD may
      be an alternative treatment option to surgery for EGCs meeting expanded
      indications, including undifferentiated-type tumors.

PMID- 29052053
TI  - Validation of the American Joint Committee on Cancer (AJCC) 8th edition stage
      system for gastric cancer patients: a population-based analysis.
AB  - BACKGROUND: Our aim was to validate the American Joint Committee on Cancer (AJCC)
      8th edition stage system for gastric cancer in the Western world and to compare
      several modifications between the 7th and 8th edition systems. METHODS: Eligible
      patients having undergone surgical resection of gastric cancer during 2004-2011
      from the Surveillance, Epidemiology, and End Results (SEER) database were
      included in the current study. Survival differences were assessed by Kaplan-Meier
      curve and log-rank tests. The discriminative power of the AJCC 8th and 7th
      editions was compared by Harrell's concordance index (c-index). RESULTS: Patients
      with pN3a and pN3b presented distinct survival outcomes, especially for cases in
      which more than 15 lymph nodes were examined. The overall (OS) and cancer
      specific survival (CSS) c-indices for the 8th edition were largely comparable
      with c-indices for the 7th edition throughout the cohort. Notably, the new
      edition improved the power of discrimination slightly in OS and CSS (c-indices:
      0.717, 0.744) compared with the 7th edition (c-indices: 0.712, 0.739) for
      patients for whom 15 or more lymph nodes were examined. The analysis of stage
      migration in the new edition revealed nonhomogeneous survival outcomes in stages
      IIIB and IIIC. CONCLUSION: The AJCC 8th stage system for gastric cancer performs
      as well as the AJCC 7th edition in the United States (USA). Importantly, when
      more than 15 lymph nodes are examined, the discriminatory performance of the new
      edition is improved.

PMID- 29052055
TI  - Correction to: HIV-1 genetic diversity, geographical linkages and antiretroviral
      drug resistance among individuals from Pakistan.
AB  - Unfortunately, the co-author's name Nouman Mughal was incorrectly published in
      the original article and the same is corrected here in this erratum.

PMID- 29052054
TI  - Suppression of the toll-like receptor 7-dependent type I interferon production
      pathway by autophagy resulting from enterovirus 71 and coxsackievirus A16
      infections facilitates their replication.
AB  - Toll-like receptors (TLRs) act as molecular sentinels, detecting invading viral
      pathogens and triggering host innate immune responses, including autophagy.
      However, many viruses have evolved a series of strategies to manipulate autophagy
      for their own benefit. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16), as
      the primary agents causing hand, foot and mouth disease (HFMD), can induce
      autophagy leading to their replication. Therefore, the objective of this study
      was to investigate whether enhanced viral replication caused by autophagy in EV71
      and CA16 infections was associated with a TLR-related signaling pathway. Our
      results demonstrate that complete autophagy and incomplete autophagy were
      observed in human bronchial epithelial (16HBE) cells infected with EV71 and CA16.
      Moreover, suppression of autophagy by the pharmacological modulator 3-MA
      significantly and clearly decreased the survival rates and viral replication of
      EV71 and CA16 in 16HBE cells. Inhibition of autophagy also enhanced the
      expression of molecules related to the TLR7-dependent type I interferon (IFN-I)
      production pathway, such as TLR7, MyD88, IRF7 and IFN-alpha/beta. Finally,
      immunofluorescence staining demonstrated that TLR7 endosome marker M6PR levels
      were clearly reduced in EV71- and CA16-infected cells, while they were markedly
      elevated in infected cells treated with 3-MA. These findings suggest that
      increased EV71 and CA16 replication meditated by autophagy in 16HBE cells might
      promote degradation of the endosome, leading to suppression of the TLR7-mediated
      IFN-I signaling pathway.

PMID- 29052056
TI  - Development of an antigen-capture ELISA for beak and feather disease virus.
AB  - Psittacine beak and feather disease (PBFD) is characterised by degenerative
      feather, feather dystrophy, and beak deformity. Sometimes acute forms can lead to
      fatal cases in nestlings. The worldwide distribution of this disease affects
      numerous species of parrots with an average prevalence of 40%, including in
      Taiwan. The pathogen of PBFD is beak and feather disease virus (BFDV), which is a
      single-stranded circular DNA virus, circovirus. To date, hemagglutination and PCR
      assays have been routinely used to detect this virus. In this study, both the
      replication-associated protein (Rep) and the structural capsid protein (Cap) were
      expressed and then used as antigens for the production of monoclonal antibodies.
      Conserved epitopes recognised by the anti-Cap and anti-Rep monoclonal antibodies
      were determined to be NFEDYRI and LSALKKM, respectively. Clinical samples
      collected from different species of parrots were tested by hemagglutination, PCR,
      and anti-Cap antigen-capture ELISA assays and the positive rates were the same at
      49%. Thus, this anti-Cap antigen-capture ELISA is able to be used for the rapid
      identification of BFDV-infected birds in a non-invasive manner.

PMID- 29052057
TI  - Characterization of the genomic sequence of a novel CRESS DNA virus identified in
      Eurasian jay (Garrulus glandarius).
AB  - Circular replication associated protein (Rep)-encoding ssDNA (CRESS DNA) viruses
      have diverse genomic architecture and are widely distributed in different
      ecosystems. In this study we characterized the complete genomic sequence of a
      novel circovirus-like virus, Garrulus glandarius associated circular virus-1
      (GgaCV-1). The genome size (1971 nt) and other features (the nonanucleotide,
      rolling circle replication motif and SF3 helicase motif) are also reminiscent of
      circoviruses. Similar genomes with uni-directionally localized and overlapping
      rep and cap genes are typical of type V CRESS DNA viruses that were identified in
      invertebrates and environmental samples of aquatic ecosystems. GgaCV-1 showed the
      highest aa identity with partial rep sequences detected in bat feces (77%) and
      with the rep (54%) and cap (42%) of Lake Sarah-associated circular virus-23 of
      New Zealand freshwater mussel origin. A dietary origin for GgaCV-1 could not be
      excluded as the virus was detected in the cloacal swab specimen of an Eurasian
      jay. Further studies may help to reveal the linkage among variable organisms
      regarding virus transmission.

PMID- 29052058
TI  - Complete genome sequence of maize yellow striate virus, a new cytorhabdovirus
      infecting maize and wheat crops in Argentina.
AB  - A rhabdovirus infecting maize and wheat crops in Argentina was molecularly
      characterized. Through next-generation sequencing (NGS) of symptomatic leaf
      samples, the complete genome was obtained of two isolates of maize yellow striate
      virus (MYSV), a putative new rhabdovirus, differing by only 0.4% at the
      nucleotide level. The MYSV genome consists of 12,654 nucleotides for maize and
      wheat virus isolates, and shares 71% nucleotide sequence identity with the
      complete genome of barley yellow striate mosaic virus (BYSMV, NC028244). Ten open
      reading frames (ORFs) were predicted in the MYSV genome from the antigenomic
      strand and were compared with their BYSMV counterparts. The highest amino acid
      sequence identity of the MYSV and BYSMV proteins was 80% between the L proteins,
      and the lowest was 37% between the proteins 4. Phylogenetic analysis suggested
      that the MYSV isolates are new members of the genus Cytorhabdovirus, family
      Rhabdoviridae. Yellow striate, affecting maize and wheat crops in Argentina, is
      an emergent disease that presents a potential economic risk for these widely
      distributed crops.

PMID- 29052060
TI  - Magnetic Poly(N-isopropylacrylamide) Nanocomposites: Effect of Preparation Method
      on Antibacterial Properties.
AB  - The most challenging task in the preparation of magnetic poly(N
      isopropylacrylamide) (Fe3O4-PNIPAAm) nanocomposites for bio-applications is to
      maximise their reactivity and stability. Emulsion polymerisation, in situ
      precipitation and physical addition were used to produce Fe3O4-PNIPAAm-1, Fe3O4
      PNIPAAm-2 and Fe3O4-PNIPAAm-3, respectively. Their properties were characterised
      using scanning electron microscopy (morphology), zeta-potential (surface charge),
      thermogravimetric analysis (stability), vibrating sample magnetometry
      (magnetisation) and dynamic light scattering. Moreover, we investigated the
      antibacterial effect of each nanocomposite against Gram-negative Escherichia coli
      and Gram-positive Staphylococcus aureus. Both Fe3O4-PNIPAAm-1 and Fe3O4-PNIPAAm-2
      nanocomposites displayed high thermal stability, zeta potential and magnetisation
      values, suggesting stable colloidal systems. Overall, the presence of Fe3O4
      PNIPAAm nanocomposites, even at lower concentrations, caused significant damage
      to both E. coli and S. aureus DNA and led to a decrease in cell viability. Fe3O4
      PNIPAAm-1 displayed a stronger antimicrobial effect against both bacterial
      strains than Fe3O4-PNIPAAm-2 and Fe3O4-PNIPAAm-3. Staphylococcus aureus was more
      sensitive than E. coli to all three magnetic PNIPAAm nanocomposites.

PMID- 29052059
TI  - Rotavirus A strains obtained from children with acute gastroenteritis in
      Mozambique, 2012-2013: G and P genotypes and phylogenetic analysis of VP7 and
      partial VP4 genes.
AB  - In Mozambique rotavirus (RV) was shown to be the greatest cause of acute
      diarrhoea in infants from 0 to 11 months, and in 2015, national rotavirus
      vaccination was introduced. As with other developing countries, there is very
      limited active strain characterisation. Rotavirus positive clinical specimens,
      collected between 2012 and 2013, have now provided information on the genotypes
      circulating in southern Mozambique prior to vaccine introduction. Genotypes G2
      (32.4%), G12 (28.0%), P[4] (41.4%) and P[6] (22.9%) (n = 157) strains were
      commonly detected with G2P[4] (42.3%) RVs being predominant, specifically during
      2013. Phylogenetic evaluation of the VP7 and VP8* encoding genes showed, for the
      majority of the Mozambican strains, that they clustered with other African
      strains based on genotype. RVA/Human-wt/MOZ/0153/2013/G2P[4], RVA/Human
      wt/MOZ/0308/2012/G2P[4] and RVA/Human-wt/MOZ/0288/2012/G12P[8] formed separate
      clusters from the other Mozambican strains with similar genotypes, suggesting
      possible reassortment. Amino acid substitutions in selected epitope regions also
      supported phylogenetic clustering. As expected, the VP7 and VP8* genes from the
      Mozambican strains differed from both the RotaTeq(r) (SC2-9) G2P[5] and
      Rotarix(r) (A41CB052A) G1P[8] genes. This study provides information on the
      genetic diversity of rotavirus strains prior to vaccine introduction and
      generates baseline data for future monitoring of any changes in rotavirus strains
      in response to vaccine pressure.

PMID- 29052061
TI  - Comparison of two new techniques for the management of malignant central airway
      obstruction: argon plasma coagulation with mechanical tumor resection versus
      cryorecanalization.
AB  - BACKGROUND: The development of central airway obstruction during malignant
      diseases is an important cause of morbidity and mortality. Endobronchial
      therapies can decrease the patient's symptoms and improve quality of life. Here,
      we compare airway recanalization methods: argon plasma coagulation with
      mechanical tumor resection (APC + MTR) and cryorecanalization (CR efficiency,
      complications, restenosis rate, and time to restenosis) in patients with
      malignant exophytic endobronchial airway obstruction. METHODS: A total of 89
      patients were included who were admitted to our hospital between 2005 and 2012.
      The data were analyzed retrospectively. Initially, a CR procedure was performed
      in 52 patients using rigid bronchoscopy under general anesthesia; the APC + MTR
      procedure was performed in 37 patients with malignant airway obstruction.
      RESULTS: The airway patency rate with APC + MTR was 97.3% (n = 36) and CR was
      80.8% (n = 42). The APC + MTR procedure was more effective than CR for
      recanalization of malignant endobronchial exophytic airway obstruction.
      Additionally, the achievement rate of airway patency with APC + MTR was
      significantly higher in tumors with distal bronchial involvement. There was no
      statistically significant difference between groups in terms of complications,
      restenosis rate, and time to restenosis. CONCLUSIONS: The APC + MTR procedure is
      preferred over CR to introduce and maintain airway patency in patients with
      malignancy-related endobronchial exophytic airway obstruction.

PMID- 29052062
TI  - How much pain relief do patients expect after cholecystectomy?
AB  - BACKGROUND: Cholecystectomy is a common operation, increasingly performed, in the
      USA, for "functional gall bladder disorder" (FGBD). Outcomes of these surgeries
      are uncertain. In planning a study of FGBD, we needed to define the best outcome
      measures. METHODS: We sought the opinions of patients (52 with FGBD and 100 with
      stones for comparison) coming to cholecystectomy. They were asked to respond in
      four ways about the minimum benefit they would count as "success." RESULTS: We
      found that most patients do not expect cholecystectomy to relieve their pain
      related disability completely, regardless of the presence or absence of stones.
      CONCLUSIONS: Future studies of the success of surgery should use patient-centered
      outcome assessments, such as PGIC (patient's global impression of change), in
      addition to objective measures of the impact of treatment on key symptoms, such
      as pain.

PMID- 29052063
TI  - Endoscopic treatment of leaks after laparoscopic sleeve gastrectomy using MEGA
      esophageal covered stents.
AB  - BACKGROUND: Sleeve gastrectomy has become one of the main bariatric procedures
      over the last few years. This can be explained by the relative simplicity and
      high effectiveness of this method. Yet, it causes complications as any other
      method. Staple line leaks are the most frequent ones. According to different
      sources, this complication may occur with 0-7% frequency. Until 2013, surgery was
      the only effective treatment method for this complication. However, reoperations
      considerably increased treatment cost and patient morbidity. The aim of this
      study is to present the possibilities of endoscopic treatment of leaks after
      laparoscopic sleeve gastrectomy. METHODS: From 2014 to 2016 14, cases of leaks
      following sleeve gastrectomy were diagnosed in our Department in Lodz. All of
      them were treated with MEGA stent in order to cover the leak site. Due to severe
      peritonitis, 3 patients had to undergo surgery prior to implantation of the
      prosthesis. Another patient underwent an unsuccessful attempt of leak closing via
      OTSC method prior to implantation of the prosthesis. Patients were nourished from
      the 3rd day after the surgery. On average, prostheses were removed on the 34th
      day after the implantation. RESULTS: The leak was fully sealed in 13 out of 14
      cases. In 10 cases the leak was fully healed. There were 2 cases of patients'
      deaths: the result of a multi-organ failure in one case and early esophageal
      perforation in the other one. The overall success rate was 90.9%. CONCLUSION:
      Sealing leaks occurring after sleeve gastrectomy with MEGA stents represent an
      effective method and should become the technique of choice.

PMID- 29052064
TI  - Determinants of variability in management of acute calculous cholecystitis.
AB  - BACKGROUND: While evidence supports early compared to delayed cholecystectomy as
      optimal management of acute calculous cholecystitis (ACC), significant
      variability in practice remains. The purpose of this study was to identify
      variables associated with early cholecystectomy, to target opportunities to
      improve adherence to best practices. METHODS: Adult patients admitted to surgical
      units with ACC at two hospitals in a university hospital network between June
      2010 and January 2015 were reviewed. Patients with concurrent pancreatitis,
      cholangitis or severe ACC (with organ system failure) were excluded. Early
      cholecystectomy was defined as surgery performed during same admission and within
      7 days of presentation. Non-operative management was defined as admission for ACC
      treated conservatively, with or without eventual delayed cholecystectomy. The
      primary outcome was early cholecystectomy versus initial non-operative
      management; secondary outcomes included time to cholecystectomy, complications,
      and total hospital length of stay (LOS). RESULTS: A total of 374 patients were
      included. Two hundred and forty six patients (66%) underwent early
      cholecystectomy, 60 (16%) were treated non-operatively and had delayed
      cholecystectomy, and 68 (18%) were only treated non-operatively. Median time to
      OR from initial presentation was 38 h [22-63] for early cholecystectomy patients
      and 69 days [29-116] for the non-operative patients who had delayed
      cholecystectomy. When comparing both groups, early cholecystectomy patients were
      younger and were treated more often at site 1. There were no differences in
      complications during hospitalization, but early cholecystectomy patients had a
      lower median total LOS (3 [2-5] vs. 5 [4-9], p < 0.001), and they had fewer
      gallstone-related events after discharge (1 vs. 18%, p < 0.001). On multiple
      logistic regression analysis, lower age, hospital site and lower risk of
      concurrent choledocholithiasis were all significantly associated with early
      cholecystectomy (p < 0.05). CONCLUSION: Our data supports early cholecystectomy
      as best practice in management of ACC with no differences in complications during
      hospitalization, shorter median LOS and fewer gallstone-related events compared
      to non-operative management. We identified patient and institutional factors
      associated with early cholecystectomy. This suggests that multiple strategies
      will be necessary to promote adherence to best practices in the management of ACC
      within our institution.

PMID- 29052065
TI  - Robotic ventral hernia repair is not superior to laparoscopic: a national
      database review.
AB  - BACKGROUND: Minimally invasive surgery (MIS) use for ventral hernia repair has
      increased over the last decade. Whether outcomes are improved by robotic
      assistance remains a subject of debate. The aim of this study is to evaluate
      outcomes (including cost, complications, length of stay (LOS), and pain
      medication utilization) in patients who underwent an open (OVHR), laparoscopic
      (LVHR), or robotic (RVHR) ventral hernia repair (VHR). METHODS: The Vizient
      database was queried using ICD-9 procedure and diagnosis codes for patients who
      underwent VHR from January 2013 to September 2015. Complications, 30-day
      readmission, mortality, LOS, cost, and intra-hospital opiate utilization were
      analyzed using IBM SPSS v.23.0.0.0. Median tests with post hoc pairwise
      comparisons, Fischer's exact, and Pearson's chi-squared test with Bonferroni
      correction were applied where appropriate, with alpha = 0.05. RESULTS: 46,799
      patients (OVHR: N = 39,505, LVHR: N = 6829, RVHR: N = 465) met the criteria and
      patients in each group had similar demographics (Table 1). OVHR was associated
      with significant increased overall complications, 30-day readmission, LOS, and
      postoperative pain use compared to RVHR or LVHR. OVHR had higher mortality and
      postoperative infection rates than LVHR. RVHR had significantly higher rates of
      complications and postoperative infections compared to LVHR, although there was
      no difference in mortality, 30-day readmission, LOS, and postoperative pain
      medication use. Mean direct cost of surgery was significantly higher for RVHR,
      followed by OVHR and LVHR. CONCLUSIONS: Overall patient outcomes were improved in
      the LVHR and RVHR groups compared to the open approach. However, RVHR patients
      did not have significant improvement compared with the LVHR group in either short
      term outcomes or opiate medication used. While RVHR surgery was the most
      expensive modality, OVHR was also significantly costlier than LVHR, which was the
      least expensive. Long-term data on recurrence could not be evaluated and should
      be studied to determine the role of robotic surgery in VHR and recurrence rates.

PMID- 29052066
TI  - Long-term clinical outcomes after intrathoracic stomach surgery: a decade of
      longitudinal follow-up.
AB  - BACKGROUND: A subset of patients with large paraesophageal hernias have more than
      75% of the stomach herniated above the diaphragm; such cases are referred to as
      intrathoracic stomach (ITS). Herein, we report longitudinal symptomatic outcomes
      over a decade after surgical ITS repair in a large patient cohort. METHODS:
      Patients who underwent surgical treatment for ITS from 01/2004 to 05/2016 were
      studied. Preoperative and follow-up data were prospectively collected. Patients
      completed a standardized symptom questionnaire 1 year postoperatively and at 2
      year intervals thereafter. RESULTS: In total, 235 patients were reviewed. The
      mean age was 70.0 +/- 11.6 years; 174 patients (74.0%) were women. Surgical
      procedures included 7 transthoracic repairs and 228 transabdominal repairs (222
      laparoscopic, 2 open, 4 laparoscopic-to-open conversions). Anti-reflux procedures
      were performed in 173 patients (73.6%). 33 patients (14.0%) had mesh
      reinforcement of hiatal closure; 11 (4.7%) underwent Collis gastroplasty. Follow
      up symptom questionnaires at 1, 3, 5, 7, 9, and 11 years were available for 81,
      48, 47, 30, 33, and 38% of patients, respectively. Significant and lasting
      symptom improvement was reported at all follow-up time points. Mean satisfaction
      scores of 9.3, 9.1, 9.3, 9.0, 9.5, and 9.8 on a 1-10 scale were recorded at the
      aforementioned intervals. CONCLUSIONS: Long-term clinical outcomes confirm that
      laparoscopic ITS repair is safe and durable, and is associated with a high degree
      of patient satisfaction and symptom resolution.

PMID- 29052067
TI  - Concomitant open ventral hernia repair: what is the financial impact of
      performing open ventral hernia with other abdominal procedures concomitantly?
AB  - BACKGROUND: Open ventral hernia repair (VHR) is often performed in conjunction
      with other abdominal procedures. Clinical outcomes and financial implications of
      VHR are becoming better understood; however, financial implications of
      concomitant VHR during other abdominal procedures are unknown. This study aimed
      to evaluate the financial implications of adding VHR to open abdominal
      procedures. METHODS: This IRB-approved study retrospectively reviewed hospital
      costs to 180-day post-discharge of standalone VHRs, isolated open abdominal
      surgeries (bowel resection or stoma closure, removal of infected mesh,
      hysterectomy or oophorectomy, panniculectomy or abdominoplasty, open appendectomy
      or cholecystectomy), performed at our institution from October 1, 2011 to
      September 30, 2014. The perioperative risk data were obtained from the local
      National Surgery Quality Improvement Program (NSQIP) database, and resource
      utilization data were obtained from the hospital cost accounting system. RESULTS:
      345 VHRs, 1389 open abdominal procedures as described, and 104 concomitant open
      abdominal and VHR cases were analyzed. The VHR-only group had lower ASA Class,
      shorter operative duration, and a higher percentage of hernias repaired via
      separation of components than the concomitant group (p < 0.001). The median
      hospital cost for VHR-alone was $12,900 (IQR: $9500-$20,700). There were
      significant increases to in-hospital costs when VHR was combined with removing an
      infected mesh (63%) or with bowel resections or stoma closures (0.7%). The
      addition of VHR did not cause a significant change in 180-day post-discharge
      costs for any of the procedures. CONCLUSIONS: This study noted decreased costs
      when combining VHR with panniculectomy or abdominoplasty and hysterectomy or
      oophorectomy. For removal of infected mesh and bowel resection or stoma closure,
      waiting, when feasible, is recommended. Given the impending changes in financial
      reimbursements in healthcare in the United States, it is prudent that future
      studies evaluate further the clinical and fiscal benefit of concomitant
      procedures.

PMID- 29052068
TI  - A Systematic review and meta-analysis of the efficacy and safety of video
      assisted anal fistula treatment (VAAFT).
AB  - BACKGROUND: Video-assisted anal fistula treatment (VAAFT) is a novel, minimally
      invasive technique for the treatment of fistula-in-ano (FIA). This review aimed
      to search the literature for the outcome of VAAFT regarding the recurrence and
      complication rates of the technique. METHODS: A systematic literature search was
      conducted in compliance with the PRISMA screening guidelines. PubMed/MEDLINE and
      Scopus were searched for articles reporting the outcomes of VAAFT procedure from
      inception through April 2017. The main outcomes were patients' characteristics,
      technical aspects, operation time, recurrence, and complication rates. RESULTS:
      Eleven studies (n = 788 patients) were included. The mean age of the patients was
      39.5 years. 66.5% of patients had high or complex FIA and 18.4% underwent
      previous fistula surgery. The internal opening of the fistula was detected in
      85.7% of patients. The mean operation time was 42 +/- 14.2 min. The weighed mean
      rate of detection of internal opening was 93.3%. Recurrence occurred in 112
      (14.2%) patients after a median follow-up of 9 months. Recurrence rates varied
      according to method of closure of internal opening from 15.3% after using
      staplers, 17.7% after suturing, to 25% after advancement flap. The weighted mean
      recurrence rate across the studies was 17.7%. The weighted mean complication rate
      was 4.8%. CONCLUSION: VAAFT may be considered an effective diagnostic tool and a
      safe method for the treatment of complex and high FIA attaining satisfactory
      outcome and acceptably low complications. Recurrence after VAAFT may be related
      to previous fistula surgery and the method of closure of the internal opening.

PMID- 29052069
TI  - Robotic single-site versus multiport laparoscopic cholecystectomy: a case-matched
      analysis of short- and long-term costs.
AB  - BACKGROUND: Multiport laparoscopy is the gold-standard approach for
      cholecystectomy, and single-port laparoscopy has been developed to further reduce
      its invasiveness. A specific robotic single-port platform (da Vinci single-site,
      Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2011, which
      could technically facilitate single-site cholecystectomy. Current data show its
      feasibility; however, detailed short- and long-term analyses of costs and
      comparisons relative to multiport laparoscopy are not available to date. METHODS:
      Patients who underwent robotic single-site cholecystectomy for benign, clinically
      noninflammatory disease between 2011 and 2015 were matched for disease, age,
      gender, BMI, ASA classification, diagnosis, and elapsed year of surgery to a
      cohort of multiport cholecystectomies. Demographic, perioperative, and long-term
      data were collected retrospectively and analyzed. Perioperative and long-term
      costs including re-operations due to the primary procedure until February 2017
      were compared across both cohorts. RESULTS: 99 patients who underwent robotic
      single-site cholecystectomy were matched to 99 patients with multiport
      cholecystectomy. A higher rate of outpatient procedures in the robotic cohort
      (31.3 vs. 17.2%, p = 0.0305) was found, and demographic parameters and
      perioperative clinical outcomes were similar. Perioperative costs were
      significantly higher for the robotic single-site patients (6158.0 vs. 4288.0 USD,
      p < 0.0001). With similar follow-up times of 59.0 and 58.9 months, respectively
      (p = 0.9552), significantly more patients of the robotic Single-Site cohort
      underwent follow-up surgery (7.1 vs. 0.0%, p = 0.0140), and follow-up costs were
      significantly higher for the robotic cohort (694.7 vs. 0.0 USD, p = 0.0145).
      CONCLUSION: With similar early postoperative clinical results and a higher rate
      of re-operations, perioperative and long-term costs are significantly higher with
      robotic Single-Site cholecystectomy compared with multiport cholecystectomy.
      Considering the unclear clinical value of robotic single-site cholecystectomy and
      the significant short- and long-term costs, a call for further research and a
      debate as to who should bear the costs beyond the ones of the gold-standard
      treatment appear reasonable.

PMID- 29052070
TI  - The feasibility of laparoscopic rectal resection in patients undergoing
      reoperation after transanal endoscopic microsurgery (TEM).
AB  - BACKGROUND: The success of transanal endoscopic microsurgery (TEM) for early
      rectal cancer depends on proper indications and strict patient selection. When
      unfavorable pathologic features are identified after TEM operation, total
      mesorectal excision is recommended to minimize the risk of recurrence. In this
      study, data were collected in a retrospective series of patients to determine the
      results of laparoscopic reoperation after TEM. METHODS: All patients underwent an
      accurate rectal-digital examination and clinical tumor staging by transanal
      endosonography, CT, and/or MRI. The histologic examination included an evaluation
      of the free margins, depth of tumor infiltration according to International Union
      Against Cancer guidelines, degree of tumor differentiation, and the presence of
      lymphovascular and perineural invasion. When a high-risk tumor was identified,
      reoperation was performed within 6 weeks from TEM. The patients were divided into
      two groups according to the procedure performed: laparoscopic anterior resection
      (LAR) or laparoscopic abdominal perineal amputation (LAPR). RESULTS: Sixty-eight
      patients (5.3%) underwent reoperation: 38 underwent LAR and 30 underwent LAPR.
      The mean operative time was 148.24 min (+/- 35.8, p = 0.62). Meanwhile, the mean
      distance of the TEM scar from the anal verge differed statistically between the
      two groups (p = 0.003) and was statistically correlated with abdominal perineal
      amputation (p = 0.0001) in multivariate analysis. Conversion to open surgery was
      required in 6 patients (15.7%) in the LAR group and 3 patients (10%) in the LAPR
      group (p = 0.38). The histologic examination revealed residual cancer cells in 3
      cases (3 pT2N0) and 1 case (1 pT3N0), respectively, and lymph node metastases in
      4 cases. No residual neoplasms were detected in the remaining 60 cases (88.3%).
      After a mean follow-up of 108 months, the overall disease-free survival was 98%
      (95% CI 88-99%). CONCLUSIONS: In our experience, reoperation after TEM using a
      laparoscopic approach is feasible and safe, with low conversion rates and optimal
      postoperative results.

PMID- 29052071
TI  - Validation of the VBLaST pattern cutting task: a learning curve study.
AB  - BACKGROUND: Mastery of laparoscopic skills is essential in surgical practice and
      requires considerable time and effort to achieve. The Virtual Basic Laparoscopic
      Skill Trainer (VBLaST-PC(c)) is a virtual simulator that was developed as a
      computerized version of the pattern cutting (PC) task in the Fundamentals of
      Laparoscopic Surgery (FLS) system. To establish convergent validity for the
      VBLaST-PC(c), we assessed trainees' learning curves using the cumulative
      summation (CUSUM) method and compared them with those on the FLS. METHODS: Twenty
      four medical students were randomly assigned to an FLS training group, a VBLaST
      training group, or a control group. Fifteen training sessions, 30 min in duration
      per session per day, were conducted over 3 weeks. All subjects completed pretest,
      posttest, and retention test (2 weeks after posttest) on both the FLS and
      VBLaST(c) simulators. Performance data, including time, error, FLS score,
      learning rate, learning plateau, and CUSUM score, were analyzed. RESULTS: The
      learning curve for all trained subjects demonstrated increasing performance and a
      performance plateau. CUSUM analyses showed that five of the seven subjects
      reached the intermediate proficiency level but none reached the expert
      proficiency level after 150 practice trials. Performance was significantly
      improved after simulation training, but only in the assigned simulator. No
      significant decay of skills after 2 weeks of disuse was observed. Control
      subjects did not show any learning on the FLS simulator, but improved continually
      in the VBLaST simulator. CONCLUSIONS: Although VBLaST(c)- and FLS-trained
      subjects demonstrated similar learning rates and plateaus, the majority of
      subjects required more than 150 trials to achieve proficiency. Trained subjects
      demonstrated improved performance in only the assigned simulator, indicating
      specificity of training. The virtual simulator may provide better opportunities
      for learning, especially with limited training exposure.

PMID- 29052072
TI  - Long-term outcomes of endoscopic submucosal dissection in comparison to surgery
      in undifferentiated-type intramucosal gastric cancer using propensity score
      analysis.
AB  - BACKGROUND: The treatment of intramucosal early gastric cancer with
      undifferentiated-type histologies (UD-EGCs) using endoscopic submucosal
      dissection (ESD) is controversial. This study aimed to compare the clinical and
      oncologic long-term outcomes of ESD and surgery for UD-EGCs. METHODS: A
      prospectively collected database of patients who underwent ESD or surgery between
      January 2006 and December 2012 was established. Patients who diagnosed with UD
      EGC and satisfied the expanded indications of ESD were included. Clinical data
      from 111 patients treated with ESD and 382 patients underwent surgery were
      analyzed, and 1-1 propensity score-matched 81 pairs of patients were also
      compared. RESULTS: In both groups, two-thirds of the UD-EGCs had signet ring cell
      (SRC)-type histology and about 90% of UD-EGCs were flat or depressed types. The
      mean size of tumors was smaller in ESD group (9.7 vs. 13.2 mm; P < 0.001). After
      propensity score-matched, case-matching covariates were not significantly
      different between the groups. Disease-free survival (DFS) was significantly
      shorter in the ESD group, but overall survival (OS) was not different between the
      two groups both in overall comparison (DFS; P < 0.001 and OS; P = 0.078) and
      propensity score-matched analysis (DFS; P < 0.001 and OS; P = 0.850). According
      to histologic type, OS of SRC histology was not different between the group, both
      in overall comparison and propensity score-matched analysis (P = 0.286 and P =
      0.210). On the other hands, OS of poorly differentiated adenocarcinoma was
      significantly shorter in ESD group in overall comparison (P = 0.007), but was not
      as so in propensity score-matched analysis (P = 0.088). CONCLUSIONS: ESD might be
      a complementary option for the treatment of UD-EGCs, especially in those with SRC
      type histology based on strict expanded indications. Nonetheless, close
      endoscopic surveillance is required because of a high incidence of intragastric
      recurrence.

PMID- 29052074
TI  - Correction to: Non-alcoholic Wernicke's encephalopathy with cortical involvement
      and polyneuropathy following gastrectomy.
AB  - In the original publication of the article, author name Hong-Shiu Chang was
      incorrectly written as Hong-Chiu Chang.

PMID- 29052073
TI  - Laparoscopy for primary cytoreduction with multivisceral resections in advanced
      ovarian cancer: prospective validation. "The times they are a-changin"?
AB  - BACKGROUND: Primary cytoreduction is the mainstay of treatment for advanced
      ovarian cancer (AOC). We developed and prospectively evaluated an algorithm to
      investigate the possible role of laparoscopic primary cytoreduction (LPC) in
      carefully selected patients, with AOC. METHODS: From June 2007 to July 2015, all
      patients with stage III-IV ovarian cancer and clinical conditions allowing
      aggressive surgery were candidate to primary cytoreduction with the aim of
      achieving residual tumor (RT) = 0. The possibility of attempting laparoscopic
      cytoreduction was carefully evaluated using strict selection criteria. The other
      patients were approached by abdominal primary cytoreduction (APC). At the end of
      LPC, an ultra-low pubic mini-laparotomy was performed to extract surgical
      specimens and to accomplish a laparoscopic hand-assisted exploration of the
      abdominal organs, in order to confirm complete excision of the disease. RESULTS:
      Of the included 66 patients, 21 were considered eligible for LPC; the remaining
      45 underwent APC. Optimal cytoreduction (i.e., RT = 0) was obtained in 95 and
      88.4% in the LPC and APC groups, respectively. No intra-operative complication
      and 4 (19%) early post-operative complications were observed among patients who
      received LPC. Patients who underwent APC had 17.8 and 46.7% intra- and early post
      operative complications, respectively. Median time to initiation of chemotherapy
      was 15 (range, 10-30) days in the LPC group and 28 (20-35) days in the APC group.
      After a median follow-up of 51 months, 2-year disease-free survival was 76.2% in
      the LPC group and 73.4% in the APC group. CONCLUSIONS: After strict selection, a
      group of patients with AOC may undergo LPC with extremely high rates of optimal
      cytoreduction, satisfactory perioperative morbidity, a short interval to
      chemotherapy, and encouraging survival outcomes. Clinical trial registration
      NCT02980185.

PMID- 29052075
TI  - Dopamine D1 receptor activation maintains motor coordination and balance in rats.
AB  - Dopamine (DA) modulates motor coordination, and its depletion, as in Parkinson's
      disease, produces motor impairment. The basal ganglia, cerebellum and cerebral
      cortex are interconnected, have functional roles in motor coordination, and
      possess dopamine D1 receptors (D1Rs), which are expressed at a particularly high
      density in the basal ganglia. In this study, we examined whether the activation
      of D1Rs modulates motor coordination and balance in the rat using a beam-walking
      test that has previously been used to detect motor coordination deficits. The
      systemic administration of the D1R agonist SKF-38393 at 2, 3, or 4 mg/kg did not
      alter the beam-walking scores, but the subsequent administration of the D1R
      antagonist SCH-23390 at 1 mg/kg did produce deficits in motor coordination, which
      were reversed by the full agonist SKF-82958. The co-administration of SKF-38393
      and SCH-23390 did not alter the beam-walking scores compared with the control
      group, but significantly prevented the increase in beam-walking scores induced by
      SCH-23390. The effect of the D1R agonist to prevent and reverse the effect of the
      D1R antagonist in beam-walking scores is an indicator that the function of D1Rs
      is necessary to maintain motor coordination and balance in rats. Our results
      support that D1Rs mediate the SCH-23390-induced deficit in motor coordination.

PMID- 29052077
TI  - Beat-to-beat blood pressure and heart rate responses to the Valsalva maneuver.
AB  - Measurement of beat-to-beat blood pressure and heart rate responses to the
      Valsalva maneuver is the basis for a highly informative autonomic function test.
      Whereas in the past this measurement required intra-arterial cannulation, the
      development of finger cuff devices that acquire arterial pressure waveforms
      indistinguishable from those recorded intra-arterially has made it possible to
      obtain accurate measurements noninvasively. In a patient with orthostatic
      hypotension, the pattern of blood pressure responses during and after the release
      of the maneuver can identify a neurogenic basis: sympathetic neurocirculatory
      failure. The quantifiable change in cardiac interbeat interval per unit change in
      systolic pressure during the maneuver can identify baroreflex-cardiovagal
      failure.

PMID- 29052076
TI  - (E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) Phenol Ameliorates LPS
      Mediated Memory Impairment by Inhibition of STAT3 Pathway.
AB  - Alzheimer's disease (AD) is pathologically characterized by an excessive
      accumulation of amyloid-beta (Abeta) fibrils within the brain. We tested the anti
      inflammatory and anti-amyloidogenic effects of (E)-2-methoxy-4-(3-(4
      methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a selective signal transducer and
      activator of transcription 3 (STAT3) inhibitor. We examined whether MMPP (5 mg/kg
      in drinking water for 1 month) prevents amyloidogenesis and cognitive impairment
      on AD model mice induced by intraperitoneal LPS (250 MUg/kg daily 7 times)
      injections. Additionally, we investigated the anti-neuroinflammatory and anti
      amyloidogenic effect of MMPP (1, 5, and 10 MUg/mL) in LPS (1 MUg/mL)-treated
      cultured astrocytes and microglial BV-2 cells. MMPP treatment reduced LPS-induced
      memory loss. This memory recovery effect was associated with the reduction of LPS
      induced inflammatory proteins; cyclooxygenase-2 (COX-2) and inducible nitric
      oxide synthase (iNOS) as well as activation of microglial cells and astrocytes in
      the brain. Furthermore, MMPP reduced LPS-induced beta-secretase and Abeta
      generation. In in vitro study, LPS-induced expression of inflammatory proteins
      and amyloidogenic proteins was decreased in microglial BV-2 cells and cultured
      astrocytes by MMPP treatment. Moreover, MMPP treatment suppressed DNA binding
      activities of the activation of STAT3 in in vivo and in vitro. These results
      indicated that MMPP inhibits LPS-induced amyloidogenesis and neuroinflammation
      via inhibition of STAT3.

PMID- 29052078
TI  - Carotid artery reactivity during sympathetic activation following acute
      resistance exercise.
AB  - OBJECTIVE: Acute resistance exercise has been shown to reduce brachial
      endothelial function. Whether there are concomitant reductions in carotid
      endothelial function remains unexplored. METHODS: Cold pressor test-mediated
      vasodilation of the carotid artery was used to assess carotid endothelial
      function in 15 young and healthy participants (age 26 +/- 1 years, body mass
      index 24 +/- 1 kg/m2) after acute resistance exercise or an inactive time control
      condition. RESULTS: Acute resistance exercise had no effect on the cold pressor
      test-mediated vasodilation compared to time control (5.8 +/- 0.8 vs 6.2 +/- 0.9%
      dilation, p > 0.05). INTERPRETATION: Carotid endothelial function may not be
      compromised following acute resistance exercise in young healthy adults.

PMID- 29052079
TI  - Contemporary changes to herding systems in China and effects on pasture quality:
      a case study in Gansu Province, 2000-2012.
AB  - Post-2000 efforts to protect China's pastoral areas are distinct from earlier
      efforts in that funding for the most recent round of policies and programs is
      commensurate with the task. Even with appropriate funding, however, effective
      methods of mitigating pasture degradation are widely disputed. The most
      controversial of the current policies include herding family resettlement,
      pasture fallow programs (herding "bans"), and the promotion of confined animal
      feeding operations (CAFOs). Ideally, the policies are intended to protect
      grassland ecological systems while assuring acceptable revenues to affected
      families and regions. This article presents a case study of 49 townships in three
      counties in central Gansu investigating the interactions among changes in mean
      interpolated annual precipitation and livestock density and pasture quality.
      Pasture quality is assessed using mean township values of the enhanced vegetation
      index (EVI) from 2000 to 2012 obtained by the MODerate-resolution Imaging
      Spectroradiometer (MODIS) sensor of the Terra satellite. The research joins
      remotely sensed environmental data, interpolated annual precipitation estimates,
      and livestock counts at the township scale for the years from 2000 to 2012 but is
      also informed by in-depth interviews with herding families and husbandry
      officials. Joining biophysical analyses of changes in pasture with archived data
      and in-depth interviews, we adopt a synthetic approach to determine changes to
      pasture quality under post-2000 policy interventions and possible reasons for
      these changes. Pasture quality has improved as CAFO livestock have increased;
      however, herders and local officials report that some of the new policies and
      programs may have important unanticipated negative impacts related to pasture
      ecology and water consumption.

PMID- 29052081
TI  - Comment to: "Long-term retromuscular and intraperitoneal mesh size changes within
      a randomized controlled trial on incisional hernia repair, including a review of
      the literature." Rogmark P., Ekberg O, Montgomery A.

PMID- 29052080
TI  - Calcaneal fractures: Where are we now?
AB  - This review article on the current management for calcaneal fractures discusses
      the advantages and disadvantages of different treatment options including the
      problems encountered. Controversies are described and the evidence reviewed. The
      management of some types of displaced intra-articular calcaneal fractures remains
      contentious; is there a preferred stabilisation method for each type of calcaneal
      fracture? How constant is the "constant fragment" in an intra-articular calcaneal
      fracture and what is the evidence for primary arthrodesis and what is its place
      in these fractures?

PMID- 29052082
TI  - Waiting for surgery: is waiting bad for anyone or everyone?
AB  - PURPOSE: For Canadians, as in many countries, waiting for elective surgery is
      expected. The duration of the wait raises questions about the maximum amount of
      time patients should wait for their surgery. The primary objective of this study
      was to test for a relationship between the length of time patients waited for
      elective hernia repair surgery and change in patients' self-reported health.
      METHODS: This study was based on a prospectively recruited longitudinal cohort of
      patients waiting for elective hernia repair surgery. Participants completed the
      PHQ-9, PEG, EQ-5D(3L) generic instruments, and the condition-specific COMI
      hernia. Multivariate regression models explored associations between patient
      reported outcomes and potential confounders, including age, sex, socio-economic
      status, and medical comorbidities. RESULTS: There were 118 participants and the
      modal age group was 61-70 years. The average wait time for participants was 22.5
      weeks. There were no relationships between the duration of participants' wait for
      hernia repair and the change in patients' self-reported health for hernia
      specific outcomes or overall health-related quality of life. DISCUSSION: There
      are gains in health-related quality of life to be realized by prioritizing
      symptomatic patients. Participants with greater pre-operative depression, pain,
      and hernia-related symptoms experienced an improvement in health prior to
      surgery, though more clarity is needed on the mechanisms that led to improved
      health. CONCLUSION: Many countries face problems with wait lists for elective
      surgery-and few have effective processes for triaging patients. This study shows
      that duration of time on the wait list was not associated with change in hernia
      patients' self-reported health.

PMID- 29052083
TI  - Patient-specific devices and population-level evidence: evaluating therapeutic
      interventions with inherent variation.
AB  - Designing and manufacturing medical devices for specific patients is becoming
      increasingly feasible with developments in 3D printing and 3D imaging software.
      This raises the question of how patient-specific devices can be evaluated, since
      our 'gold standard' method for evaluation, the randomised controlled trial (RCT),
      requires that an intervention is standardised across a number of individuals in
      an experimental group. I distinguish several senses of patient-specific device,
      and focus the discussion on understanding the problem of variations between
      instances of an intervention for RCT evaluation. I argue that, despite initial
      appearances, it is theoretically possible to use RCTs to evaluate some patient
      specific medical devices. However, the argument reveals significant difficulties
      for ensuring the validity of such trials, with implications for how we should
      think about methods of evidence gathering and regulatory approaches for these
      technologies.

PMID- 29052084
TI  - The apoptotic, cytotoxic and genotoxic effect of novel binuclear boron-fluoride
      complex on endometrial cancer.
AB  - Endometrial cancer (EC) is one of the most common types of gynecologic cancer of
      the female genital tract; it considered being the fourth leading death factor
      among other types of cancer. Therefore, developing new anti-cancer agents are
      crucial for cancer treatment. Based on the potential of Schiff based complexes
      for the induction of apoptosis, Schiff base compounds, and their metal complexes
      displayed excellent anticancer properties. In this current study,
      antiproliferative activity of [L(BF2)2] as a novel binuclear boron-fluoride
      complex was examined to preliminary research in eight different cell lines, HELA,
      DU-145, PC3, DLD-1, ECC-1, PNT1-A, HT-29, and MCF-7, it was found to have a
      potent, suppressive effect on human endometrial adenocarcinoma cell line ECC-1.
      Based on this data, later investigated its apoptotic, cytotoxic, and genotoxic
      properties on human endometrial adenocarcinoma cell line ECC-1 in different
      concentrations. Apoptotic and cytotoxic tests such as single cell gel
      electrophoresis assay (comet assay), DNA fragmentation laddering, acridine orange
      test for DNA damage, and ELISA for apoptotic measurement was performed. We also
      gauged the oxidative status by evaluating total antioxidant status (TAS) and
      total oxidant status (TOS). Oxidative stress index (OSI) was calculated too. As a
      result [L(BF2)2] has been found to have a marvelous effect on ECC-1 cells,
      especially in damaging their DNA and cause a series of reactions lead to
      apoptosis. Taken together, it suggests that the [L(BF2)2] complex can induce the
      apoptotic pathway of endometrial cancer cells and is a possible candidate for
      future cancer treatment studies.

PMID- 29052085
TI  - Comparison of Young Patients with Gastric Cancer in the United States and China.
AB  - BACKGROUND: This study aimed to compare the clinicopathologic characteristics and
      stage-specific prognosis of young patients with gastric cancer (GC) after
      curative resection (R0) in the United States and China. METHODS: Data were
      collected on young patients (age <=40 years) undergoing R0 resection at one U.S.
      (n = 79) and one Chinese (n = 257) institution. Patient, surgical, and pathologic
      variables and stage-specific survival rates were compared. Factors associated
      with 5-year disease-specific survival (DSS) were determined via multivariate
      analysis. RESULTS: Tumor location was most often proximal in U.S. patients and
      distal in Chinese patients. The Chinese patients had more advanced-stage tumors,
      with a greater number of positive lymph nodes identified. Preoperative
      chemotherapy was administered more often in the United States. The 5-year overall
      survival (p = 0.07) and DSS (p = 0.07) did not differ statistically between the
      U.S. and Chinese cohorts. Among the patients with early GC receiving surgery
      alone, DSS did not differ significantly between the two cohorts (p = 0.44). Among
      the patients with advanced GC, DSS was comparable between the U.S. patients
      receiving preoperative chemotherapy plus surgery and the Chinese patients
      receiving surgery plus postoperative chemotherapy (p = 0.85). Lauren
      classification, depth of invasion, number of metastatic lymph nodes, and type of
      gastrectomy, but not country, were independent predictors of DSS. CONCLUSIONS:
      Tumor features and therapeutic strategies among young patients with GC differ
      between the United States and China. Survival is comparable between young
      patients with advanced GC receiving preoperative chemotherapy plus surgery in the
      United States and those receiving surgery plus postoperative chemotherapy in
      China, suggesting that the outcomes for young patients with GC are stage
      dependent but not country specific.

PMID- 29052086
TI  - Tissue and urinary KIM-1 relate to tumor characteristics in patients with clear
      renal cell carcinoma.
AB  - The objective of this prospective follow-up trial was to ascertain whether the
      urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1)
      expression and with the pathological characteristics of clear renal cell
      carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially
      nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical
      study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy
      volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit
      and normalized by urinary creatinine. Immunohistochemical staining (monoclonal
      anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative
      analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively
      stained tubules). Both markers were interpreted in terms of the tumor
      characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage,
      tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery
      RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to
      controls, such as uKIM-1 was statistically higher in RN than in PN patients.
      Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was
      documented in all nephrectomized patients. Significant associations were achieved
      between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially
      with tumor size and grade. Based on the accomplished associations, we found uKIM
      1 as a highly sensitive marker for cRCC diagnosis. The clinical trial
      registration number: 1110-2012.

PMID- 29052089
TI  - Regulation of Neurotransmitter Release by Amyloid Precursor Protein Through
      Synapsin Phosphorylation.
AB  - Abnormal processing of amyloid precursor protein (APP) and aggregation of the
      Abeta peptide are known to play a key role in the pathogenesis of Alzheimer
      disease, but the function of endogenous APP under normal physiological conditions
      remains poorly understood. In this study, we investigated presynaptic changes in
      APP knockout (KO) mice. We demonstrate that both sucrose-induced
      neurotransmission and synaptic depletion in response to high frequency
      stimulation are significantly enhanced in APP KO compared to wild type
      littermates. In addition, the level of phosphorylated forms of synapsins, but not
      total synapsins, is elevated in the KO mice. Furthermore, we show that the
      inhibition of L-type calcium channels normalizes phosphorylated synapsins and
      slows down the high frequency induced synaptic depletion in APP KO mice. These
      results suggest a new mechanism by which APP regulates synaptic vesicle dynamics
      through synapsin-dependent phosphorylation.

PMID- 29052087
TI  - Does green tea consumption increase urinary oxalate excretion? Results of a
      prospective trial in healthy men.
AB  - OBJECTIVE: To investigate the impact of green tea on urinary oxalate excretion in
      healthy male volunteers. MATERIALS AND METHODS: The oxalate concentrations after
      different brewing times (2-60 min) of different qualities (2-8 g) of green tea
      were measured in in vitro experiment. In in vivo experiment, the effects on urine
      composition were assessed in 12 healthy men with an age of 24-29 years. Each
      subject was requested to collect two 24-h urine samples under normal dietary
      conditions. Green tea prepared from tea bags containing 2 g of tea leafs was
      consumed by the subjects for 7 consecutive days, and 24-h urine samples were
      collected and analyzed on days 6 and 7. After 3-week washout interval, all
      subjects consumed green tea containing 4 g of leaf tea for another 7 consecutive
      days. Two 24-h urine samples were collected on the last 2 days. Urine volume, pH,
      calcium, magnesium, sodium, phosphate, potassium, chloride, citrate, oxalate,
      urate and creatinine were measured. RESULTS: In the in vitro experiments, oxalate
      in solution increased with brewing time (p < 0.05) and tea quality (p < 0.05). In
      the in vivo experiment, 24-h urinary oxalate increased significantly (0.24 +/-
      0.09 mmol to 0.32 +/- 0.13 mmol, p = 0.045) when tea was prepared from 2-g bags
      of green leaf tea. Consumption of green tea containing 4 g of leaf tea resulted
      in 24-h urinary oxalate increase (0.25 +/- 0.25 mmol to 0.34 +/- 0.22 mmol, p =
      0.041). CONCLUSIONS: In vitro studies showed that there was a gradual increase in
      solution concentrations of oxalate that was associated with increased brewing
      time and increased quality of green tea. Studies in normal men showed that green
      tea consumption was associated with increased urinary exertion of oxalate.

PMID- 29052088
TI  - Fascin-1 Contributes to Neuropathic Pain by Promoting Inflammation in Rat Spinal
      Cord.
AB  - Neuropathic pain is a complicated clinical syndrome caused by heterogeneous
      etiology. Despite the fact that the underlying mechanisms remain elusive, it is
      well accepted that neuroinflammation plays a critical role in the development of
      neuropathic pain. Fascin-1, an actin-bundling protein, has been proved to be
      involved in the processing of diverse biological events including cellular
      development, immunity, and tumor invasion etc. Recent studies have shown that
      Fascin-1 participates in antigen presentation and the regulation of pro
      inflammatory agents. However, whether Fascin-1 is involved in neuropathic pain
      has not been reported. In the present study we examined the potential role of
      Fascin-1 by using a rodent model of chronic constriction injury (CCI). Our
      results showed that Fascin-1 increased rapidly in dorsal root ganglions (DRG) and
      spinal cord (SC) after CCI. The increased Fascin-1 widely expressed in DRG,
      however, it localized predominantly in microglia, seldom in neuron, and hardly in
      astrocyte in the SC. Intrathecal injection of Fascin-1 siRNA not only suppressed
      the activation of microglia and the release of pro-inflammatory mediators, but
      also attenuated the mechanical allodynia and thermal hyperalgesia induced by CCI.

PMID- 29052090
TI  - Decreased serum proNGF concentration in patients with Parkinson's disease.
AB  - Parkinson's disease (PD), a progressive and age-related neurodegenerative
      condition, is a common neurodegenerative disorder. However, no validated
      biomarkers for PD have been identified to date. Accumulating evidence supports
      the role of proNGF-p75NTR-sortilin signaling in the neurodegeneration and
      pathogenesis of PD. The aim of our study was to investigate alterations in serum
      proNGF concentrations in PD patients and related anxiety. Seventy-seven
      consecutive PD patients and 39 healthy controls were enrolled, and clinical data
      were collected. Modified Hoehn-Yahr Staging Scale, Unified Parkinson's Disease
      Rating Scale (UPDRS), and Hamilton Anxiety (HAMA) Scale scores were assessed upon
      admission. Serum proNGF concentration was compared between that of PD patients
      and healthy controls. Pearson correlation coefficients were determined to explore
      the relationship between proNGF concentration and UPDRS, Hoehn-Yahr, and HAMA
      scores. Received operating characteristic (ROC) curves and proNGF optimal cutoff
      point were used to distinguish PD and related anxiety. The median concentration
      of proNGF was significantly lower (p = 0.000) in PD patients (94.91 ng/L, range
      85.92-118.06 ng/L) compared with that of healthy controls (106.67 ng/L, range
      102.39-122.06 ng/L). The optimal proNGF cutoff point for distinguishing PD
      patients was 102.29 ng/L, and the sensitivity and specificity values were 87.0
      and 100%, respectively. proNGF concentration positively correlated with UPDRS (r
      = 0.281, p = 0.013), Hoehn-Yahr (r = 0.260, p = 0.023), and HAMA (r = 0.276, p =
      0.015) scores. Our results indicate that serum proNGF concentration may represent
      a biomarker for PD and its role in the pathogenesis of PD thus warrants further
      investigation.

PMID- 29052091
TI  - THC/CBD oromucosal spray in patients with multiple sclerosis overactive bladder:
      a pilot prospective study.
AB  - Lower urinary tract dysfunctions (LUTDs) are commonly reported in multiple
      sclerosis (MS) patients and are mainly related to neurogenic overactive bladder
      (OAB). The aim of this observational study was to assess the effect of a
      tetrahydrocannabinol-cannabidiol (THC/CBD) oromucosal spray on resistant OAB by
      means of clinical and instrumental tools. Twenty-one MS patients were screened,
      and 15 cases have been evaluated. They underwent a specific clinical assessment
      (overactive bladder symptom score, OABSS) and a urodynamic assessment evaluating
      the maximal cystometric capacity (CCmax), bladder compliance (Qmax), maximum
      detrusor pressure (Pdet max), detrusor pressure at the first desire (Pdet first),
      bladder volume at the first desire (BVFD), leakage volume (LV), and post-void
      residual volume (PVR), before and after 4 weeks of THC/CBD administration. A
      complete neurological evaluation, including the assessment of their spasticity
      using the Modified Ashworth Scale (MAS) and the spasticity 0-10 numerical rating
      scale (NRS), was performed at the same times. Mobility was evaluated through the
      25-ft walking-time test (T25-WT). The THC/CBD treatment successfully reduced the
      OAB symptoms (p = 0.001). Regarding the urodynamic findings after the end of
      treatment, PVR was significantly reduced (p = 0.016). Regarding the urodynamic
      findings after the end of treatment, PVR was significantly reduced (p = 0.016),
      while BVFD and CCmax were increased although the difference was not statistically
      significant. THC/CBD oromucosal spray has shown to be effective in improving
      overactive bladder symptoms in MS patients demonstrating a favorable impact on
      detrusor overactivity.

PMID- 29052093
TI  - Emerging small molecule approaches to enhance the antimyeloma benefit of
      proteasome inhibitors.
AB  - Multiple myeloma (MM) is a clonal plasma cell malignancy which, despite recent
      treatment advances, remains incurable in the vast majority of the over 118,000
      patients in the USA afflicted with this disease. Treatment of MM has dramatically
      improved in the past decade with the introduction of new drugs into therapeutic
      strategies in both the frontline and relapse settings that has led to a
      significant improvement in the median overall survival (OS). These drugs have
      been incorporated into clinical guidelines and transformed the treatment approach
      to MM. Numerous classes of antimyeloma agents, i.e., alkylators, steroids,
      proteasome inhibitors, immunomodulatory agents, deactylase inhibitors, and
      monoclonal antibodies, are now FDA-approved and can be combined in doublet or
      triplet regimens. Moreover, many patients do not respond to therapy and those
      that do eventually relapse. Emerging therapies that may overcome drug resistance
      and improve MM treatment include that inhibit regulatory and Ub-processing
      components of the proteasome, a specialized variant of the proteasome known as
      the immunoproteasome, proteolysis-targeting chimeric molecules (PROTACS and
      Degronomids). Emerging strategies also include accessory plasmacytoid dendritic
      cells (pDCs), vaccines, checkpoint inhibitors, and chimeric antigen receptor
      engineered T (CAR-T) cells. Advances in understanding proteasome and plasma cell
      biology may allow for earlier treatment of MM patients using rationally informed
      combination therapies with curative potential.

PMID- 29052092
TI  - A 72-h intervention for improvement of the rate of optimal antibiotic therapy in
      patients with bloodstream infections.
AB  - Antimicrobial stewardship programs are implemented to optimize the use of
      antibiotics and control the spread of antibiotic resistance. Many antimicrobial
      stewardship interventions have demonstrated significant efficacy in reducing
      unnecessary prescriptions of antibiotics, the duration of antimicrobial therapy,
      and mortality. We evaluated the benefits of a combination of rapid diagnostic
      tests and an active re-evaluation of antibiotic therapy 72 h after the onset of
      bloodstream infection (BSI). All patients with BSI from November 2015 to November
      2016 in a 1100-bed university hospital in Rome, where an Infectious Disease
      Consultancy Unit (Unita di Consulenza Infettivologica, UDCI) is available, were
      re-evaluated at the bedside 72 h after starting antimicrobial therapy and
      compared to two pre-intervention periods: the UDCI was called by the ward
      physician for patients with BSI and the UDCI was called directly by the
      microbiologist immediately after a pathogen was isolated from blood cultures.
      Recommendations for antibiotic de-escalation or discontinuation significantly
      increased (54%) from the two pre-intervention periods (32% and 27.2%, p <
      0.0001). Appropriate escalation also significantly increased (22.5%) from the pre
      intervention periods (8.1% and 8.2%, p < 0.0001). The total duration of
      antibiotic therapy decreased with intervention (from 21.9 days [standard
      deviation, SD 15.4] in period 1 to 19.3 days [SD 13.3] in period 2 to 17.7 days
      in period 3 [SD 11.5]; p = 0.002) and the length of stay was significantly
      shorter (from 29.7 days [SD 29.3] in period 1 to 26.8 days [SD 24.7] in period 2
      to 24.2 days in period 3 [SD 20.7]; p = 0.04) than in the two pre-intervention
      periods. Mortality was similar among the study periods (31 patients died in
      period 1 (15.7%), 39 (16.7%) in period 2, and 48 (15.3%) in period 3; p = 0.90).
      Rapid diagnostic tests and 72 h re-evaluation of empirical therapy for BSI
      significantly correlated with an improved rate of optimal antibiotic therapy and
      decreased duration of antibiotic therapy and length of stay.

PMID- 29052094
TI  - Severe Physical Complications among Survivors of Stevens-Johnson Syndrome and
      Toxic Epidermal Necrolysis.
AB  - INTRODUCTION: Few studies have reported the physical complications among Stevens
      Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) survivors. OBJECTIVE:
      The aim of this study was to comprehensively characterize the physical
      complications among SJS/TEN survivors and to learn about patients' perspectives
      of surviving SJS/TEN. METHODS: SJS/TEN survivors older than 18 years of age were
      assessed by different methods: a medical interview; a questionnaire assessing
      patients' perspectives; thorough skin, oral mucous membrane, and ophthalmic
      examinations; and a retrospective assessment of medical records. RESULTS: Our
      cohort consisted of 17 patients with a mean time of 51.6 +/- 74.7 months (median
      9, range 1-228) following SJS/TEN. The most common physical complications
      identified in the medical examination were post-inflammatory skin changes (77%),
      cutaneous scars (46%), dry eyes (44%), symblepharon, and chronic ocular surface
      inflammation (33% each). Novel physical sequelae included chronic fatigue (76%)
      and pruritus (53%). We also found a novel association between the number of
      mucous membranes affected in the acute phase of SJS/TEN and hair loss during the
      6 months following hospital discharge; hair loss was reported in 88% of the group
      of patients who had three or more mucous membranes affected versus 29% of
      patients who had less than three mucous membranes involved (p = 0.0406).
      Following hospital discharge due to SJS/TEN, 59% of patients were followed by a
      dermatologist, although 88% had dermatological complications; 6% were followed by
      an ophthalmologist, even though 67% had ophthalmological complications; and 6% of
      female survivors were followed by a gynecologist, even though 27% had
      gynecological complications. CONCLUSION: Survivors of SJS/TEN suffer from severe
      physical complications impacting their health and lives that are mostly under
      recognized and not sufficiently treated by medical professionals.

PMID- 29052095
TI  - Grass phasiRNAs and male fertility.
AB  - Recent studies have indicated that a special type of small noncoding RNAs, phased
      small-interfering RNAs (phasiRNAs) play crucial roles in many cellular processes
      of plant development. PhasiRNAs are generated from long RNA precursors at
      intervals of 21 or 24 nt in plants, and they are produced from both protein
      coding gene and long noncoding RNA genes. Different from those in eudicots, grass
      phasiRNAs include a special class of small RNAs that are specifically expressed
      in reproductive organs. These grass phasiRNAs are associated with gametogenesis,
      especially with anther development and male fertility. In this review, we
      summarized current knowledge on these small noncoding RNAs in male germ cells and
      their possible biological functions and mechanisms in grass species.

PMID- 29052097
TI  - The Processing of Relative Clause Attachment as a Tool for Resolving a Problem in
      Typology of Relative Clauses: Preliminary Evidence from Thai Data.
AB  - In typological literature, there has been disagreement as to whether there should
      be distinction between relative clauses (RCs) and nominal sentential complements
      (NSCs) in pro-drop languages such as Japanese, Chinese, Korean, Khmer and Thai.
      In pro-drop languages, nouns can be dropped when its reference can be retrieved
      from context. Therefore, what has been defined as a gap in RCs (i.e., the
      controversial element hereafter) and has often been used for differentiating RCs
      from NSCs might actually be a zero pronoun, making syntactic structures of RC and
      NSCs indistinguishable. This article reviews the study of the processing of RC
      attachment in Thai and discusses how its results provide preliminary evidence
      supporting that RCs and NSCs in Thai are syntactically different constructions
      and the controversial element in RCs is not a zero pronoun. The article suggests
      a new promising tool for investigating an unresolved typological problem.

PMID- 29052096
TI  - Life paths of patients with transthyretin-related familial amyloid polyneuropathy
      Val30Met: a descriptive study.
AB  - Transthyretin-related familial amyloid polyneuropathy Val30Met is a fatal
      progressive disease. It is a rare hereditary amyloidosis, manifesting as a
      sensorimotor neuropathy and autonomic dysfunction. It begins during adulthood and
      is a disabling disease, posing a great psychological burden to patients and their
      families. Our aim was to describe and characterize life events related to the
      disease and discuss its psychosocial implications. Social and demographic data
      and a questionnaire on history of family and personal disease, and biographic
      events, were applied to 209 subjects attending an outpatient specialized clinic.
      Descriptive and statistical analyses were performed. They were 84 men and 127
      women belonging to three groups: pre-symptomatic carriers, patients, and subjects
      with no established diagnosis. Most subjects were married/lived with a partner
      and had children (mean of 4). Most (96.3%) had contact with the disease before
      having a diagnosis; the affected or at-risk parent was the mother in 53.8% and
      the father in 43.3%; 71.8% of these had deceased. At their parent's death, many
      subjects were aged under 10 (9.9%), 10-14 (15.5%), or 15-24 years (31.7%). Most
      were under age 14 (44.9%) at their parent's disease onset; 37.2% referred this
      brought life changes with psychological and familial impact; most had been
      parent's caregivers; 7.5% had not been raised by the parents. Some (8.4%)
      declined to know their genetic tests results for over 1 year. Parent's disease
      and death are very common early in these patient's lives. During childhood or
      youth, many subjects became caregivers, implying changes in family roles. This
      disease and its life implications pose a significant psychosocial burden since
      childhood. TTR-FAP patients and their relatives are highly vulnerable to
      emotional stress and psychopathology during their lifetime. Psychological and
      psychiatric support, implying a multidisciplinary group, must thus be available
      for all of them.

PMID- 29052099
TI  - The novel ethylene-responsive factor CsERF025 affects the development of fruit
      bending in cucumber.
AB  - KEY MESSAGE: Overexpression of CsERF025 induces fruit bending by promoting the
      production of ethylene. Cucumber fruit bending critically affects cucumber
      quality, but the mechanism that causes fruit bending remains unclear. To better
      understand this mechanism, we performed transcriptome analyses on tissues from
      the convex (C1) and concave (C2) sides of bending and straight (S) fruit at 2
      days post anthesis (DPA). We identified a total of 281 differentially expressed
      genes (DEGs) from both the convex and concave sides of bent fruit that showed
      significantly different expression profiles relative to straight fruits. Of these
      281 DEGs, 196 were up-regulated (C1/S_C2/S) and 85 were down-regulated
      (C1/S_C2/S). Among the 196 up-regulated DEGs, the transcriptional levels of genes
      related to ethylene biosynthesis and signaling pathways were significantly higher
      in bending fruit compared with straight fruit. CsERF025 showed the largest
      difference in expression between bending and straight fruit. CsERF025 is an
      AP2/ERF gene encoding a protein that localizes to the nucleus. Overexpression of
      this gene increased the bending rate of cucumber fruits and increased the angle
      of bending. CsERF025 increased both the expression of ethylene biosynthesis
      related genes and the production of ethylene. The application of exogenous 1
      aminocyclopropane-l-carboxylic acid (ACC) to straight fruits from control plants
      promoted fruit bending. Thus, CsERF025 enhances the production of ethylene and
      thereby promotes fruit bending in cucumber.

PMID- 29052098
TI  - Comparative transcriptome analysis reveals whole-genome duplications and gene
      selection patterns in cultivated and wild Chrysanthemum species.
AB  - KEY MESSAGE: Comparative transcriptome analysis of wild and cultivated
      chrysanthemums provides valuable genomic resources and helps uncover common and
      divergent patterns of genome and gene evolution in these species. Plants are
      unique in that they employ polyploidy (or whole-genome duplication, WGD) as a key
      process for speciation and evolution. The Chrysanthemum genus is closely
      associated with hybridization and polyploidization, with Chrysanthemum species
      exhibiting diverse ploidy levels. The commercially important species, C.
      morifolium is an allohexaploid plant that is thought to have originated via the
      hybridization of several Chrysanthemum species, but the genomic and molecular
      evolutionary mechanisms remain poorly understood. In the present study, we
      sequenced and compared the transcriptomes of C. morifolium and the wild Korean
      diploid species, C. boreale. De novo transcriptome assembly revealed 11,318 genes
      in C. morifolium and 10,961 genes in C. boreale, whose functions were annotated
      by homology searches. An analysis of synonymous substitution rates (Ks) of
      paralogous and orthologous genes suggested that the two Chrysanthemum species
      commonly experienced the Asteraceae paleopolyploidization and recent genome
      duplication or triplication before the divergence of these species. Intriguingly,
      C. boreale probably underwent rapid diploidization, with a reduction in
      chromosome number, whereas C. morifolium maintained the original chromosome
      number. Analysis of the ratios of non-synonymous to synonymous nucleotide
      substitutions (Ka/Ks) between orthologous gene pairs indicated that 107 genes
      experienced positive selection, which may have been crucial for the adaptation,
      domestication, and speciation of Chrysanthemum.

PMID- 29052100
TI  - Acute Localized Exanthematous Pustulosis (ALEP): Review of Literature with Report
      of Case Caused by Amoxicillin-Clavulanic Acid.
AB  - Acute localized exanthematous pustulosis (ALEP) is a localized form of acute
      generalized exanthematous pustulosis, characterized by acute onset of multiple
      nonfollicular, pinhead-sized, sterile pustules following drug administration.
      Antibiotics, especially beta-lactams and macrolides, have been implicated in the
      majority of cases, although eruption after nonsteroidal antiinflammatory drugs
      and many other medications has also been reported. Skin reaction arises quickly
      within a few hours, resolving rapidly within a few days without treatment, and it
      is usually accompanied by fever and neutrophilic leukocytosis. We report herein
      all cases of ALEP described in literature, adding the case of a 35-year-old woman
      admitted to our hospital with outbreak of erythematous pustules on her face,
      neck, and chest after amoxicillin-clavulanic acid treatment.

PMID- 29052101
TI  - Effects of Hydraulic Soil Properties on Vegetation Pattern Formation in Sloping
      Landscapes.
AB  - Current models of vegetation pattern formation rely on a system of weakly
      nonlinear reaction-diffusion equations that are coupled by their source terms.
      While these equations, which are used to describe a spatiotemporal planar
      evolution of biomass and soil water, qualitatively capture the emergence of
      various types of vegetation patterns in arid environments, they are
      phenomenological and have a limited predictive power. We ameliorate these
      limitations by deriving the vertically averaged Richards' equation to describe
      flow (as opposed to "diffusion") of water in partially saturated soils. This
      establishes conditions under which this nonlinear equation reduces to its weakly
      nonlinear reaction-diffusion counterpart used in the previous models, thus
      relating their unphysical parameters (e.g., diffusion coefficient) to the
      measurable soil properties (e.g., hydraulic conductivity) used to parameterize
      the Richards equation. Our model is valid for both flat and sloping landscapes
      and can handle arbitrary topography and boundary conditions. The result is a
      model that relates the environmental conditions (e.g., precipitation rate, runoff
      and soil properties) to formation of multiple patterns observed in nature (such
      as stripes, labyrinth and spots).

PMID- 29052102
TI  - Changes in cerebellar functional connectivity and autonomic regulation in cancer
      patients treated with the Neuro Emotional Technique for traumatic stress
      symptoms.
AB  - PURPOSE: A growing number of research studies have implicated the cerebellum in
      emotional processing and regulation, especially with regard to negative emotional
      memories. However, there currently are no studies showing functional changes in
      the cerebellum as a result of treatment for traumatic stress symptoms. The Neuro
      Emotional Technique (NET) is an intervention designed to help improve symptoms
      related to traumatic stress using an integrative approach that combines
      emotional, cognitive, and motor processing, with a particular focus on autonomic
      nervous system regulation. In this study, we evaluated whether the NET
      intervention alters functional connectivity in the brain of patients with
      traumatic stress symptoms associated with a cancer-related event. We hypothesized
      that the NET intervention would reduce emotional and autonomic reactivity and
      that this would correlate with connectivity changes between the cerebellum and
      limbic structures as well as the brain stem. METHODS: We enrolled patients with a
      prior cancer diagnosis who experienced distressing cancer-related memories
      associated with traumatic stress symptoms of at least 6 months in duration.
      Participants were randomized to either the NET intervention or a waitlist
      control. To evaluate the primary outcome of neurophysiological effects, all
      participants received resting-state functional blood oxygen level-dependent
      (BOLD) magnetic resonance imaging (rs-fMRI) before and after the NET
      intervention. In addition, autonomic reactivity was measured using heart rate
      response to the traumatic stimulus. Pre/post comparisons were performed between
      the NET and control groups. RESULTS: The results demonstrated significant changes
      in the NET group, as compared to the control group, in the functional
      connectivity between the cerebellum (including the vermis) and the amygdala,
      parahippocampus, and brain stem. Likewise, participants receiving the NET
      intervention had significant reductions in autonomic reactivity based on heart
      rate response to the traumatic stimulus compared to the control group.
      CONCLUSIONS: This study is an initial step towards establishing a neurological
      signature of treatment effect for the NET intervention. Specifically, functional
      connectivity between the cerebellum and the amygdala and prefrontal cortex appear
      to be associated with a reduction in autonomic reactivity in response to
      distressing cancer-related memories. IMPLICATIONS FOR CANCER SURVIVORS: This
      study contributes to the understanding of possible mechanisms by which
      interventions like NET may help reduce emotional distress in cancer patients who
      suffer from traumatic stress symptoms.

PMID- 29052103
TI  - Patterns of specificity and diversity in species of Paraorygmatobothrium Ruhnke,
      1994 (Cestoda: Phyllobothriidae) in Moreton Bay, Queensland, Australia, with the
      description of four new species.
AB  - A survey of tapeworms of galeomorph sharks from Moreton Bay (Queensland,
      Australia) identified a complex of species of Paraorygmatobothrium Ruhnke, 1994
      infecting 11 carcharhiniform and two orectolobiform species. Combined
      morphological and multi-locus molecular analyses (based on the 28S nuclear
      ribosomal RNA and partial mitochondrial NADH dehydrogenase subunit 1 genes)
      revealed the presence of 12 species of Paraorygmatobothrium; four species
      (Paraorygmatobothrium christopheri n. sp., P. harti n. sp., P. sinclairtaylori n.
      sp. and P. ullmanni n. sp.) are considered to be new to science and are formally
      described, four represent known species, and four lack sufficient morphological
      data to allow definitive identification. In contrast to previous records for the
      genus, four of the species found in this study exhibited low host specificity [P.
      orectolobi (Butler, 1987) Ruhnke, 2011, P. sinclairtaylori, P. ullmanni and
      Paraorygmatobothrium sp. 3], three stenoxenic species were each found in two
      closely-related sharks (P. orectolobi, P. ullmanni and Paraorygmatobothrium sp.
      3) and one euryxenic species was found in five species from two shark families
      (P. sinclairtaylori). One species was found to exhibit mild morphologically
      plasticity (P. orectolobi), with size range being associated with different shark
      species. Conversely, collections of almost morphologically indistinguishable
      specimens from single shark species were found to represent multiple species of
      Paraorygmatobothrium. The findings of this study indicate that the description of
      species of this genus on the basis of morphological data alone is problematic and
      that the inclusion of multi-locus molecular data is essential for future work on
      Paraorygmatobothrium. Host specificity, morphology and phylogenetic relatedness
      of species of Paraorygmatobothrium are explored.

PMID- 29052105
TI  - Impact of previous drug-eluting stent restenosis in non-left main coronary artery
      lesions on long-term outcomes after left main coronary artery stenting: an
      observation from the AOI-LMCA registry.
AB  - : We hypothesized that patients who had previous target-lesion revascularization
      (TLR) for DES restenosis in non-left main coronary artery (LMCA) lesions might
      have a higher risk for restenosis after subsequent DES implantation for a de novo
      unprotected LMCA lesion. Among 1809 patients enrolled in the Assessing Optimal
      Percutaneous Coronary Intervention for LMCA (AOI-LMCA) registry, which is a
      retrospective 6-centre registry of consecutive patients undergoing LMCA stenting
      in Japan, 251 patients with previous DES implantation for non-LMCA lesions were
      subdivided into the 2 groups with (N = 56) or without (N = 195) previous TLR in
      non-LMCA lesions. The risk for TLR for LMCA was neutral between the prior TLR for
      DES restenosis group and the no prior TLR for DES restenosis group [hazard ratio
      (HR) 0.99, 95% confidence interval (CI) 0.44-2.02, P = 0.98]. The risks for both
      TLR caused by restenosis of the LMCA main branch, and second TLR for restenosis
      after first TLR for LMCA were also neutral between the 2 groups (HR 0.42, 95% CI
      0.10-1.25, P = 0.13, and HR 0.59, 95% CI 0.03-3.63, P = 0.60, respectively). In
      conclusion, prior TLR for DES restenosis in non-LMCA lesions was not associated
      with worse long-term clinical outcomes after DES implantation for de novo
      unprotected LMCA lesions. CLINICAL TRIAL REGISTRATION: Assessing Optimal
      Percutaneous Coronary Intervention for Left Main Coronary Artery Stenting
      Registry (AOI LMCA Stenting Registry). http://www.umin.ac.jp/ctr/index/htm/ .
      Unique Identifier: UMIN000014706.

PMID- 29052106
TI  - Effect of low-density lipoprotein cholesterol on the geometry of coronary
      bifurcation lesions and clinical outcomes of coronary interventions in the J
      REVERSE registry.
AB  - We investigated the effect of low-density lipoprotein cholesterol (LDL-C) on the
      geometry of coronary bifurcation lesions. A total of 300 non-left main
      bifurcation lesions in 298 patients from J-REVERSE registry were classified
      according to statin treatment status at admission (NT, non-treated; ST, statin
      treated) and were further subdivided based on LDL-C levels with a cutoff of 100
      mg/dL (NT-high, n = 76 lesions; NT-low, n = 46; ST-high, n = 99 and ST-low, n =
      79). In addition, a group with strict control of LDL-C (< 70 mg/dL) was defined
      (ST-SC; n = 19). The NT-high group had higher angled bifurcations compared to
      that in the NT-low group (59.1 degrees  +/- 21.5 degrees  vs. 50.3 degrees  +/-
      18.6 degrees , p = 0.02). In the multivariate analysis, NT-high group was an
      independent factor contributing on generation of higher angled (> 80 degrees )
      lesion (odds ratio 3.77, 95% CI 1.05-13.5, p = 0.04). The NT-low group had more
      men (95.6 vs. 81.6%, p = 0.03), and greater plaque volume in the distal main
      vessel (7.1 +/- 3.2 mm3/mm vs. 5.7 +/- 2.7 mm3/mm, p = 0.02), compared to those
      in the NT-high group. LDL-C was more likely to remain high after statin treatment
      in younger patients (65.3 +/- 3.6 years vs. 68.6 +/- 8.4 years, p = 0.02) and
      current smokers (36.7 vs. 16.9%, p = 0.004). The ST-SC group had limited luminal
      volume expansion compared to that in the ST-high group (proximal: 6.7 +/- 1.4
      mm3/mm vs. 7.7 +/- 2.3 mm3/mm, p = 0.04; distal: 5.3 +/- 1.5 mm3/mm vs. 6.5 +/-
      1.9 mm3/mm, p = 0.04), regardless of similar plaque volumes. Elevated LDL-C is
      likely to promote the generation of higher angled bifurcation lesions and
      multiple risk factors lead to a more progressed bifurcation lesion even in
      patients with lower LDL-C levels.

PMID- 29052104
TI  - Anticoagulation prescribing patterns in patients with cancer.
AB  - Cancer is a known hypercoagulable state that leads to an increased risk of venous
      thromboembolism (VTE). Low molecular weight heparin remains the preferred
      anticoagulant for VTE in patients with cancer over vitamin K antagonist. However,
      the preferred anticoagulant in prevention of stroke and systemic embolism in
      atrial fibrillation (AF) in patients with cancer has yet to be determined. The
      direct oral anticoagulants (DOACs) are increasingly being utilized; however their
      role in cancer has only recently been investigated. The objective of this
      retrospective cohort was to describe real-world anticoagulation prescribing
      patterns in cancer patients at a large academic medical center between January 1,
      2013 and October 31, 2016. We sought to assess the safety, tolerability, and
      efficacy of DOACs in patients with cancer for either VTE and/or AF. Patient
      demographic, clinical characteristics, as well as bleeding and thrombotic events
      were collected. There were 214 patients in our analysis, of which 71 patients
      (33%) received a DOAC [apixaban (n = 22), dabigatran (n = 17), and rivaroxaban (n
      = 32)]. There were fewer bleeding events and/or discontinuations in the DOAC
      group compared to enoxaparin (13 vs. 27, p = 0.022). There was no difference in
      major or minor bleeds or thromboembolic events in comparing DOAC to enoxaparin or
      DOAC to warfarin. This was a retrospective, single-institution study assessing
      the safety and efficacy of DOACs compared to warfarin or enoxaparin in patients
      with cancer. DOACs may represent an alternative to warfarin or enoxaparin in
      patients with cancer for VTE and/or stroke reduction in AF.

PMID- 29052107
TI  - Aspects of Morality and Law Enforcement in Today's Science in Post-Soviet
      Countries.
AB  - Many reports independently confirm that even more than a quarter of a century
      after the collapse of the Soviet Union, the results of research and development
      in those countries that were under its influence are insufficient in comparison
      to the rest of the world. Given that human intelligence is not distributed
      unevenly and that science is a powerful driving force for the future of an
      economy, there is a hidden problem, which, if it can be resolved, may release
      great economic potential. The first generation of researchers from Armenia, Czech
      Republic, Georgia, Slovakia and Ukraine, who successfully completed their
      education after the political revolution, were surveyed. The survey revealed many
      similarities with regards to ethics, but that there is mounting evidence that the
      main cause of the current situation is the state of the local legal systems. The
      conclusion was drawn that a conceptual change in staffing within the relevant
      legal systems is required to release potential and stimulate wealth creation.

PMID- 29052108
TI  - Risk factors for complications among breast cancer patients treated with post
      mastectomy radiotherapy and immediate tissue-expander/permanent implant
      reconstruction: a retrospective cohort study.
AB  - BACKGROUND: The use of post-mastectomy radiotherapy (PMRT) following immediate
      breast reconstruction has increased recently, and its safety is becoming a major
      concern. We aimed to evaluate the complication rates of PMRT to immediate tissue
      expander/permanent implant (TE/PI)-based reconstructions for breast cancer and
      its association with radiotherapy timing (irradiation to TE or PI). METHODS: We
      retrospectively reviewed the cases of breast cancer patients who underwent
      mastectomy, immediate TE/PI reconstruction, and PMRT between January 2003 and
      December 2014. The rates of complications including reconstruction failure, re
      operation, and infection were estimated by Kaplan-Meier analysis. The risk
      factors including radiotherapy timing were analyzed by log-rank test and
      multivariate Cox proportional hazard model. RESULTS: A total of 81 patients were
      included. Median follow-up was 32 months (range 2-120 months). Radiotherapy
      consisted of 50 Gy to the reconstructed breast and supraclavicular region in most
      cases. Total reconstruction failure, re-operation, and infection rates were 12.3,
      13.6, and 11.1%, and 5-year cumulative reconstruction failure, re-operation, and
      infection rates were 16.7, 16.6, and 12.2%, respectively. No significant
      differences were observed in complication rates with respect to radiotherapy
      timing. In multivariate analysis, age 55 years and older was a significant risk
      factor for complications (P < 0.05). CONCLUSION: There were no significant
      differences in rates of reconstruction failure, re-operation, or infection with
      regard to radiotherapy timing. PMRT to reconstructed breasts of older patients
      aged 55 years or over can be expected to result in more complications than in
      younger patients.

PMID- 29052109
TI  - Assessments of Opportunities to Improve Antibiotic Prescribing in an Emergency
      Department: A Period Prevalence Survey.
AB  - INTRODUCTION: Approximately 30% of all outpatient antimicrobials are
      inappropriately prescribed. Currently, antimicrobial prescribing patterns in
      emergency departments (ED) are not well described. Determining inappropriate
      antimicrobial prescribing patterns and opportunities for interventions by
      antimicrobial stewardship programs (ASP) are needed. METHODS: A retrospective
      chart review was performed among a random sample of non-admitted, adult patients
      who received an antimicrobial prescription in the ED from January 1 to December
      31, 2015. Appropriateness was measured using the Medication Appropriateness
      Index, and was based on provider adherence to local guidelines. Additional
      information collected included patient characteristics, initial diagnoses, and
      other chronic medication use. RESULTS: Of 1579 ED antibiotic prescriptions in
      2015, we reviewed a total of 159 (10.1%) prescription records. The most
      frequently prescribed antimicrobial classes included penicillins (22.6%),
      macrolides (20.8%), cephalosporins (17.6%), and fluoroquinolones (17.0%). The
      most common indications for antibiotics were bronchitis or upper respiratory
      tract infection (URTI) (35.1%), followed by skin and soft tissue infection (SSTI)
      (25.0%), both of which were the most common reason for unnecessary prescribing
      (28.9% of bronchitis/URTIs, 25.6% of SSTIs). Of the antimicrobial prescriptions
      reviewed, 39% met criteria for inappropriateness. Among 78 prescriptions with a
      consensus on appropriate indications, 13.8% had inappropriate dosing, duration,
      or expense. CONCLUSION: Consistent with national outpatient prescribing,
      inappropriate antibiotic prescribing in the ED occurred in 39% of cases with the
      highest rates observed among patients with bronchitis, URTI, and SSTI.
      Antimicrobial stewardship programs may benefit by focusing on initiatives for
      these conditions among ED patients. Moreover, creation of local guideline
      pocketbooks for these and other conditions may serve to improve prescribing
      practices and meet the Core Elements of Outpatient Stewardship recommended by the
      Centers for Disease Control and Prevention.

PMID- 29052110
TI  - Developing a Novel Model to Improve Research and care for Cancer Survivors: a
      Feasibility Study.
AB  - Despite a growing number of clinical trials and supportive care programs for
      cancer survivors, recruitment of patients for these opportunities during the
      survivorship phase of care is challenging. We piloted a novel process to
      systematically educate patients about available research studies and supportive
      care programs as part of a survivorship care visit. Between 3/2015 and 8/2015,
      patients seen in the Adult Survivorship Program who had not previously received a
      treatment summary and survivorship care plan (TS/SCP) were provided with one
      accompanied by a list of survivorship research studies and care programs tailored
      to their diagnosis. Survivorship providers discussed the opportunities and
      recorded whether the patient was interested in relevant studies and placed
      referrals to study staff. Following the visit, we tracked study enrollment and
      surveyed patients about their experience. Fifty of 56 (89%) pilot participants
      completed the survey. Almost all (98%) reported that the TS/SCP visit and
      document helped with knowledge of research opportunities and supportive care
      interventions. Following receipt of the TS/SCP, 44% were interested in at least
      one study and in further follow-up with research staff. Of the 30 survivors
      eligible for at least one study, 6 (20%) have enrolled in at least one study to
      date. This pilot program demonstrates that the systematic sharing of available
      clinical studies and supportive care programming as part of a survivorship care
      plan visit is feasible and well received by cancer survivors and may facilitate
      and enhance accrual to clinical trials in the survivorship phase of care.

PMID- 29052111
TI  - Targeted massively parallel sequencing characterises the mutation spectrum of
      PALB2 in breast and ovarian cancer cases from Poland and Ukraine.
AB  - Loss-of-function germline mutations in the PALB2 gene are associated with an
      increase of breast cancer risk. The purpose of this study was to characterise the
      spectrum of PALB2 mutations in women affected with breast or ovarian cancer from
      South-West Poland and West Ukraine. We applied Hi-Plex, an amplicon-based
      enrichment method for targeted massively parallel sequencing, to screen the
      coding exons and proximal intron-exon junctions of PALB2 in germline DNA from
      unrelated women affected with breast cancer (n = 338) and ovarian cancer (n = 89)
      from Poland (n = 304) and Ukraine (n = 123). These women were at high-risk of
      carrying a genetic predisposition to breast and/or ovarian cancer due to a family
      history and/or early-onset disease. Targeted-sequencing identified two frameshift
      deletions: PALB2:c.509_510del; p.R170Ifs in three women affected with breast
      cancer and PALB2:c.172_175del;p.Q60Rfs in one woman affected with ovarian cancer.
      A number of other previously described missense (some predicted to be damaging by
      PolyPhen-2 and CADD) and synonymous mutations were also identified in this
      population. This study is consistent with previous reports that
      PALB2:c.509_510del and PALB2:c.172_175del are recurrent mutations associated with
      breast cancer predisposition in Polish women with a family history of the
      disease. Our study contributes to the accumulating evidence indicating that PALB2
      should be included in genetic testing for breast cancer susceptibility in these
      populations to enhance risk assessment and management of women at high-risk of
      developing breast cancer. This data could also contribute to ongoing work that is
      assessing the possible association between ovarian cancer risk and PALB2
      mutations for which there is currently no evidence.

PMID- 29052112
TI  - Divergences in learning and memory among wild zebrafish: Do sex and body size
      play a role?
AB  - Given its diverse ecological distribution, zebrafish has great potential for
      investigations on the effect of habitat characteristics on cognition. Studies
      were conducted on four wild-caught zebrafish populations to understand the role
      of native habitat, sex, and body size in determining learning through a novel
      task associated with a food reward. The habitat variables, namely, the relative
      abundances of zebrafish and predatory fish and the substrate and vegetation
      diversity, were quantified during fish sampling. Fish were subjected to a novel
      task to find a food reward in a maze over successive training trials followed by
      a test for memory. Performances of subjects were based on time taken to find the
      food reward and number of mistakes made during trials, and tests for memory. The
      experiments revealed significant differences in learning rates and memory across
      populations. Males made significantly fewer mistakes than females only within two
      populations. No relationship between performance and body size was observed. The
      differences in learning and memory among wild zebrafish could be due to
      differences in predation, complexity, and stability of the native habitats. These
      findings suggest the possible role of multiple interacting factors in determining
      learning and memory among populations and point to a need for incorporating
      effects of several factors in future studies.

PMID- 29052113
TI  - Stimulus preexposure speeds or slows subsequent acquisition of associative
      learning depending on learning test procedures and response measure.
AB  - Prior exposure to a conditioned stimulus (CS) typically results in latent
      inhibition-slower acquisition of associative learning about that stimulus in
      subsequent training. Here, we found that CS preexposure had different effects on
      the appetitive conditioning of rats with a sucrose unconditioned stimulus (US)
      depending on training test procedures, the similarity of preexposure and training
      procedures, and the choice of response measure. Preexposure to a visual or an
      auditory stimulus produced facilitation of acquisition of food-cup-directed
      responding when both of those cues were (separately) paired with sucrose delivery
      in the training test (Experiments 1 and 3). By contrast, the same preexposure
      procedure resulted in latent inhibition of food-cup learning if the second
      stimulus in the test phase was of the same modality as the preexposed stimulus
      (Experiment 2). In Experiment 3, latent inhibition was enhanced if both phases
      included a single CS or both phases included both auditory and visual CSs,
      compared to treatments in which only one CS was presented in one phase but two
      CSs were presented in the other phase. In Experiment 4, preexposure of an
      auditory cue slowed subsequent learning about it if the context was salient but
      enhanced learning if the context was of weaker salience. Finally, a measure of
      general activity revealed latent inhibition after preexposure in all conditions
      in all 4 experiments. We discuss the results within several classes of latent
      inhibition theories, none of which provides a comprehensive account.

PMID- 29052115
TI  - Train-the-trainer program on cardiovascular health for community pharmacists in
      Malaysia.
AB  - Background Studies have highlighted the benefits of having community pharmacists
      to deliver cardiovascular screening to patients. However, only few of such
      trainings are provided in Malaysia. Objective To describe the implementation and
      evaluation of a cardiovascular train-the-trainer program for community
      pharmacists. Method Community pharmacists' attended a 5 h train-the-trainer
      program. A pre and post-training survey was administered to participants who
      attended the workshop to determine their requirements for education and
      effectiveness of the training provided. Results Forty community pharmacists
      participated and were trained with 35 of them completing both the pre and post
      training assessment. Participants self-reported confidence, knowledge and ability
      to conduct a workshop on cardiovascular health increased between 0.22 and 0.75
      points post-training (p < 0.05). The program was rated as very good or excellent
      by 55% of participants. Eight participants implemented the program at 6 months
      follow-up within their own pharmacy organisations to further train another 114
      participants on cardiovascular health. Conclusion Participation in a train-the
      trainer program significantly increases community pharmacists' perceived ability
      and confidence in conducting a cardiovascular health workshop.

PMID- 29052114
TI  - Urban Form, Air Pollution, and Health.
AB  - PURPOSE OF REVIEW: Urban form can impact air pollution and public health. We
      reviewed health-related articles that assessed (1) the relationships among urban
      form, air pollution, and health as well as (2) aspects of the urban environment
      (i.e., green space, noise, physical activity) that may modify those
      relationships. RECENT FINDINGS: Simulation and empirical studies demonstrate an
      association between compact growth, improved regional air quality, and health.
      Most studies are cross-sectional and focus on connections between transportation
      emissions and land use. The physical and mental health impacts of green space,
      public spaces that promote physical activity, and noise are well-studied aspects
      of the urban environment and there is evidence that these factors may modify the
      relationship between air pollution and health. Urban form can support efforts to
      design clean, health-promoting cities. More work is needed to operationalize
      specific strategies and to elucidate the causal pathways connecting various
      aspects of health.

PMID- 29052116
TI  - Patients' knowledge on oral anticoagulant treatment in Hungary.
AB  - Background A key element for an effective and safe oral anticoagulant treatment
      (OAT) is to have the relevant information delivered to patients in an easy-to
      understand way and thus have them apply this knowledge in their own therapy.
      Objective To assess knowledge about OAT, reveal knowledge gaps and identify at
      risk patients in terms of limited knowledge about their anticoagulant therapy.
      Setting Community pharmacies in Hungary. Methods This descriptive cross-sectional
      study used a structured, validated, self-developed questionnaire to assess
      patients' knowledge about OAT. Scores were calculated on each domain and the
      association between knowledge and patients' or treatment characteristics were
      analysed. Responses in all domains were assessed to identify at-risk patients and
      knowledge gaps. Main outcome measures Knowledge and knowledge gaps on OAT, and
      risk factors for limited knowledge. Results The questionnaire developed based on
      four validated questionnaires passed the field test and had a good internal
      consistency (Cronbach alpha = 0.795). Our full patient population (N = 427) had a
      mean percentage score of 59.39 (29.7% good, 41.2% average, 29.0% poor knowledge
      on OAT). Poor knowledge level was found to significantly correlate with advanced
      age (> 75 years), lower education, diagnosis of atrial fibrillation, and
      unawareness of the indication of OAT. The lowest frequency of correct answers
      regarded the questions on drug interactions (10.2%) and diet (11.4%). Pharmacists
      were infrequently indicated as the healthcare professionals to share information
      with regarding OAT (12.7%). Conclusion Findings of our study offer a valuable
      insight into the required directions of developing new strategies for patient
      education to improve knowledge on the treatment with oral anticoagulants.

PMID- 29052117
TI  - Clinical impact of an interdisciplinary patient safety program for managing drug
      related problems in a long-term care hospital.
AB  - Background Medication reviews intended to identify drug-related problems (DRPs)
      have been researched in primary care, acute care and nursing homes rather than in
      long-term care hospitals (LTCHs). Objectives To assess the clinical impact of an
      interdisciplinary pharmacotherapy quality improvement and patient safety program
      in elderly patients with polypharmacy admitted to an LTCH. Setting An
      interventional, longitudinal, prospective study was conducted in a Spanish LTCH
      Method A total of 162 elderly (>= 70 years) patients with polypharmacy (>= 5
      medications) were included. Pharmacist conducted the pharmacotherapy follow-up of
      patients (reconciliation, pharmacotherapeutic optimization, educational
      interviews) from admission to discharge. Demographic, clinical and treatment
      related variables were recorded. Main outcome measured Clinical impact of the
      program by DRP-based effectiveness and drug-related morbidity (DRM)-based safety
      indicators. Results 895 DRPs (median of 5 (1-23)) were identified in 153 (94.4%)
      patients. The most common DRPs were unnecessary drug (25.3%), dosage too high
      (24.9%) and a need for additional drug (24.8%). The most frequent pharmacotherapy
      recommendations were individualizing the dosage regimen (29.6%) and stopping
      (27.3%) or starting (21.9%) a drug. The mean implementation rate of
      pharmacotherapy recommendations was 90.9%. The effectiveness indicator revealed a
      94.9% of prevented or resolved DRPs. The safety indicator showed an 89.3% of
      prevented or resolved DRM. Therefore, the program prevented or resolved 92.5% of
      adverse effects and 91.7% of suboptimal responses or therapeutic failures.
      Conclusion This interdisciplinary patient safety program seems to be a valuable
      approach to identify, prevent and resolve the high number of DRPs and potential
      DRM that elderly patients with polypharmacy admitted to an LTCH present.

PMID- 29052118
TI  - Challenging Conventions of Bullying Thresholds: Exploring Differences between Low
      and High Levels of Bully-Only, Victim-Only, and Bully-Victim Roles.
AB  - Using a commonly accepted threshold of 2 to 3 times per month as a marker of
      bullying-involvement from noninvolvement, approximately 30% of U.S. students
      report being a bully, victim, or both. Although variation in the frequency of
      involvement exists, infrequent engagement (less than 2 to 3 times a month) is
      generally considered noninvolved. However, the question remains: Do these
      differences have implications for behavioral health patterns, including substance
      use, depression and school connectedness? The present study used a district-wide
      random cluster sample of 66 middle and high schools in a mid-size city. The study
      population consisted of 3,221 middle school (53.4%) and high school (45.6%)
      students, with 48.7% females, 44.6 males, and 6.7% youth identifying with another
      gender category. These youth were racially diverse, with the modal category being
      Black (36.0%). Based on student survey response, we report, (a) the frequency and
      intensity of bullying behaviors, (b) common patterns of involvement, and (c)
      demographic and individual-level risk factors associated with these patterns.
      Analyses resulted in nine bully types, with substantial differences in bullying
      involvement intensity based on gender, race, school connectedness, and mental
      health. Perhaps most striking, the majority of youth (70.9%) were involved in
      some level of bullying perpetration, victimization, or both, when accounting for
      the accumulation of low frequency involvement (e.g., once, twice, or a few times)
      across multiple bullying behaviors. Implications for adolescent development and
      prevention are described.

PMID- 29052120
TI  - Can Parenting Microprotections Buffer Against Adolescents' Experiences of Racial
      Discrimination?
AB  - Previous research highlights the importance and pervasiveness of racial
      discrimination for minority youth in the United States. Adolescents may
      experience either personal or group race-based discrimination. While past
      research found both forms of discrimination are harmful to well-being it is
      unknown whether parental microprotections, which may buffer against the negative
      effects of discrimination, protect against both forms of discrimination. Informed
      by ecological frameworks the present study examined whether parent
      microprotections (parental warmth/acceptance, cultural socialization, preparation
      for bias) buffered the effects of personal and group discrimination on
      adolescents' depressive symptoms. Participants were African American early
      adolescents (N = 129; 58% female) and their parents (90% mothers). Adolescents
      attended a Midwestern, Title 1, urban, public middle school and completed surveys
      in their homerooms and parents completed paper-pencil surveys at home, online or
      surveys via telephone. Multiple regression analyses were conducted to test
      whether adolescents' personal and group discrimination at school were related to
      their reports of depressive symptoms and evaluate whether parent microprotections
      buffered these associations. Results showed that parental microprotections
      moderated the effects of personal discrimination on depressive symptoms but did
      not buffer the effects of group discrimination. These results highlight the
      importance of distinguishing between personal and group discrimination. Further,
      additional protective factors need to be identified and tested to better
      understand parental actions that potentially buffer the negative effects of
      discrimination.

PMID- 29052122
TI  - [Study of prevalence of Toxoplasma gondii oocysts in the cats of Nouakchott].
AB  - The aim of the work was to evaluate the prevalence of Toxoplasma gondii oocyst
      shedding on a sample of 100 cats in five districts of Nouakchott, Mauritania. The
      faecal flotation method revealed that 23% +/- 0.08 of cats which underwent the
      test excreted oocysts and the prevalence was influenced by age and sex. Excretion
      rates were significantly higher in neighborhoods of Basra (27.8 +/- 0.2), Elmina
      (25 +/- 0.13) and Netegue (20 +/- 0.35). The average parasite number was less
      than 5 oocysts/5 g faeces. Hence, the results suggest that cats have an important
      role in the transmission of the zoonosis in Nouakchott.

PMID- 29052121
TI  - Co-Occurring Posttraumatic Stress Disorder and Depression Among Young Children.
AB  - The purpose of this study was to examine differences in: (1) mental health
      emotional and behavioral problems between young children experiencing PTSD with
      and without MDD; (2) the incidence of caregiver PTSD and MDD between children
      with PTSD +/- MDD; and (3) the number of traumatic events and interpersonal
      versus non-interpersonal nature of trauma events among children whose parents
      sought child trauma-focused treatment. Sixty-six caregivers of children aged 3-7
      with PTSD completed semi-structured interviews regarding caregiver and child
      diagnoses, and caregivers completed self-report measures regarding child
      symptomatology. Results indicated that young children with PTSD + MDD had
      significantly higher internalizing symptoms, dissociative symptoms, and
      posttraumatic stress severity than those without comorbid MDD. There were no
      significant group differences in the incidence of caregiver PTSD or MDD, or the
      number or types of traumatic events. Future research to understand the unique
      contributors to the etiology of MDD in the context of PTSD among young children
      is needed.

PMID- 29052123
TI  - Successful chemotherapy with modified FOLFIRINOX for pancreatic acinar cell
      carcinoma.
AB  - Abdominal ultrasonography revealed a pancreatic mass in a 67-year-old man with
      diabetes mellitus. Endoscopic ultrasound-guided fine needle aspiration led to the
      histological diagnosis of acinar cell carcinoma. The clinical stage was
      determined to be IVb based on findings of multiple metastatic lesions in the
      liver and lymph nodes, as well as splenic vein infiltration. Because the patient
      was not a surgical candidate, he underwent chemotherapy with modified FOLFIRINOX.
      In the absence of any severe adverse events, 12 courses of chemotherapy were
      delivered, resulting in marked shrinkage of both the primary and metastatic
      lesions. The outcome was judged to be a partial response, which was maintained
      even 9 months from the introduction of the chemotherapy. The results of this case
      suggest that modified FOLFIRINOX is safe and effective in the treatment of
      pancreatic acinar cell carcinoma.

PMID- 29052124
TI  - Endoscopic biliary stenting for unresectable malignant hilar obstruction.
AB  - Palliative drainage is the primary treatment option for unresectable malignant
      hilar biliary obstruction (UMHBO) to improve the prognosis and quality of life.
      Currently, endoscopic biliary drainage is considered as a first-line treatment
      for UMHBO as well as for distal biliary obstruction. Self-expanding metal stents
      (SEMSs) are preferred over plastic stents (PSs) in patients with life expectancy
      of >3 months. However, endoscopic treatment of UMHBO is often more challenging
      and complex than that of distal biliary obstruction. Although no consensus exists
      on the optimal method for biliary drainage because of the lack of well-designed,
      large-scale randomized control trials, several essential aspects of various
      optimal methods have been studied. Presently, technological developments in this
      field are under way and newly designed or modified stenting devices for UMHBO are
      being developed. In this review, we assess the optimal stenting strategy for
      UMHBO based on the previous literature, focusing on the stent type (PS vs SEMS),
      the liver volume to be drained, unilateral (single) vs bilateral (multiple) stent
      deployment, and bilateral stenting method (stent-in-stent vs side-by-side).

PMID- 29052125
TI  - Differences in innate IFNgamma and IL-17 responses to Bordetella pertussis
      between BALB/c and C57BL/6 mice: role of gammadeltaT cells, NK cells, and
      dendritic cells.
AB  - Cell-mediated immune responses characterized by the secretion of IFNgamma and IL
      17 play an important role in the immune response to Bordetella pertussis (B.
      pertussis). We investigated innate sources of IFNgamma and IL-17 upon stimulation
      of spleen cells from BALB/c (B/c) and C57BL/6 (B6) mice with heat-killed B.
      pertussis (hkBp). Spleen cells from B/c mice secreted less IFNgamma and more IL
      17 than those from B6 mice. Innate IFNgamma was produced predominantly by NK
      cells in B/c mice and by CD8 T cells and NK cells in B6 mice. Innate IL-17 was
      produced primarily by gammadeltaT cells in both mouse strains. The secretion of
      IFNgamma was abrogated by anti-IL-12, and the production of IL-17 was abolished
      by anti-IL-1beta- and anti-IL23-neutralizing antibodies. B/c dendritic cells
      (DCs) stimulated with hkBp secreted significantly more IL-1beta and less IL-12
      than B6 DCs. Differences in JNK phosphorylation in DCs suggest that this pathway
      plays a role in the differences between B/c and B6 strains. Mixed cultures of DCs
      and gammadeltaT cells from B/c and B6 showed that cytokines from DCs as well as
      gammadeltaT cell-intrinsic factors contributed to the robust innate IL-17
      response in B/c strain. Stimulation of gammadeltaT cells with IL-1beta and IL-23
      was sufficient for IL-17 secretion whereas IL-12 inhibited the secretion of IL
      17. A larger fraction of gammadeltaT cells were gammadeltaT-17 cells in B/c mice
      than B6 mice. Our data indicate important roles for genetically determined
      factors in the innate IFNgamma and IL-17 responses to B. pertussis.

PMID- 29052126
TI  - Genetic characterization of H9N2 avian influenza viruses isolated from poultry in
      Poland during 2013/2014.
AB  - The study presents molecular characterization of H9N2 avian influenza (AI)
      isolates from field outbreaks in turkeys that occurred in Poland in 2013-2014.
      Sequences of all gene segments of one isolate from 2013
      (A/turkey/Poland/14/2013(H9N2)) and two isolates from 2014
      (A/turkey/Poland/08/2014(H9N2), A/turkey/Poland/09/2014(H9N2)) were obtained and
      analyzed in search of the phylogenetic relationship and molecular markers of
      zoonotic potential or increased pathogenicity. All gene segments were shown to
      originate from the wild bird reservoir and the close relationship of the analyzed
      isolates proved the link between the outbreaks in 2013 and 2014. However,
      remarkable molecular differences between isolates from 2013 to 2014 were
      identified, including mutation in the HA cleavage site (CS) leading to conversion
      from the PAASNR*GLF to the PAASKR*GLF motif and truncation of the PB1-F2 protein.
      Additionally, T97I substitution in the PA protein in A/turkey/Poland/08/2014 was
      detected which can be responsible for enhanced activity of viral polymerase in
      mammalian cells. However, experimental infection of mice with both isolates from
      2014 showed their low pathogenicity, and no statistically significant differences
      in virus replication were observed between the viruses. Nevertheless, these
      findings indicate the dynamic evolution of H9N2 in the field emphasizing the need
      for monitoring of the situation in terms of H9N2 AI in Europe.

PMID- 29052128
TI  - Overview of Infectious Causes of Human Cancers.
AB  - Emerging evidence has demonstrated that almost each person is infected at least
      one potentially cancer-causing organism; however, only a small proportion of
      infected individual develops cancer. In this review, to elucidate the potential
      role of infectious organisms in the development and progression of human cancers,
      we summarize the previous history and current understandings of infection
      associated cancers and highlight the common molecular mechanisms of cancers
      caused by infectious agents and their potential cofactors, which may bring us to
      effectively prevent and reduce the infection-associated cancers in the future.

PMID- 29052127
TI  - Letter to the Editor: CORR Insights(r): Does Extracellular DNA Production Vary in
      Staphylococcal Biofilms Isolated From Infected Implants Versus Controls?

PMID- 29052129
TI  - Hepatitis B Virus-Associated Hepatocellular Carcinoma.
AB  - Liver cancer is the fifth most common cancer worldwide in men and the ninth in
      women. It is also the second most common cause of cancer mortality.
      Hepatocellular carcinoma (HCC) is the most common type of liver cancer. About 350
      million people globally are chronically infected with HBV. Chronic hepatitis B
      virus (HBV) infection accounts for at least 50% cases of HCC worldwide. Other non
      HBV factors may increase HCC risk among persons with chronic HBV infection. Both
      indirect and direct mechanisms are involved in HCC oncogenesis by HBV. HCC
      promoting HBV factors include long-lasting infection, high levels of HBV
      replication, HBV genotype, HBV integration, specific HBV mutants, and HBV-encoded
      oncoproteins (e.g., HBx and truncated preS2/S proteins). Recurrent liver
      inflammation caused by host immune responses during chronic HBV infection can
      lead to liver fibrosis and cirrhosis and accelerate hepatocyte turnover rate and
      promote accumulation of mutations. Major breakthroughs have been achieved in the
      prevention of HBV-associated HCC with HBV vaccines and antiviral therapies.

PMID- 29052130
TI  - Human Papillomavirus-Related Cancers.
AB  - Human papillomavirus (HPV) infection is associated with several cancers such as
      cancer in the cervix, vagina, and vulva and oropharyngeal, anal, penile, and
      cutaneous carcinomas, which is regarded as a great public health concern. The
      association between HPV is the strongest with cervical cancer because almost all
      such malignancies contain viral DNA, notably HPV types 16 and 18. The present
      chapter summarizes recent progresses of the HPV-associated cancers regarding
      epidemiology, molecular biology, HPV testing, vaccination, and treatment of HPV
      related cancers.

PMID- 29052131
TI  - Merkel Cell Polyomavirus: A New DNA Virus Associated with Human Cancer.
AB  - Merkel cell polyomavirus (MCPyV or MCV) is a novel human polyomavirus that has
      been discovered in Merkel cell carcinoma (MCC), a highly aggressive skin cancer.
      MCPyV infection is widespread in the general population. MCPyV-associated MCC is
      one of the most aggressive skin cancers, killing more patients than other well
      known cancers such as cutaneous T-cell lymphoma and chronic myelogenous leukemia
      (CML). Currently, however, there is no effective drug for curing this cancer. The
      incidence of MCC has tripled over the past two decades. With the widespread
      infection of MCPyV and the increase in MCC diagnoses, it is critical to better
      understand the biology of MCPyV and its oncogenic potential. In this chapter, we
      summarize recent discoveries regarding MCPyV molecular virology, host cellular
      tropism, mechanisms of MCPyV oncoprotein-mediated oncogenesis, and current
      therapeutic strategies for MCPyV-associated MCC. We also present epidemiological
      evidence for MCPyV infection in HIV patients and links between MCPyV and non-MCC
      human cancers.

PMID- 29052133
TI  - EBV Infection and Glucose Metabolism in Nasopharyngeal Carcinoma.
AB  - To establish persistent infection in cells, viruses evolve strategies to alter
      host cellular pathways to regulate cell proliferation and energy metabolism which
      support viral infection. Epstein-Barr virus (EBV) undergoes both lytic and latent
      infection to achieve persistent and lifelong infection in human. EBV readily
      infects human B cells, driving their transformation to proliferative
      lymphoblastoid cell lines (LCL), and eventually establishes lifelong latent
      infection in memory B cells. In contrary, EBV undergoes lytic replication upon
      infection into normal epithelial cells which is essential for the replication of
      EBV genome and production of infectious viral particles for transmission through
      saliva. EBV shuttles between B cells and epithelial cells to complete its
      infection cycle. EBV infection is closely associated with nasopharyngeal
      carcinoma (NPC) and is present in practically 100% of undifferentiated NPC. In
      contrast to undergo lytic infection of normal pharyngeal epithelium, EBV
      establishes latent infection in NPC. The switch from lytic infection to latent
      infection may represent an early and essential step in the development of NPC.
      Recent studies in both B cells and NPC cells latently infected with EBV reveal
      alterations in cell metabolism to support persistent and latent EBV infection.
      Events underlying the switching of lytic to latent EBV infection in NPC cells are
      largely undefined. Molecular events and alterations of cell metabolism are likely
      to play crucial roles in switching EBV infection from lytic to latent in NPC
      cells. Latent EBV infection and expression of viral genes, including LMP1, LMP2,
      and possibly EBV-encoded micro RNAs, may play essential roles in alterations of
      cell metabolism to support NPC pathogenesis. Alteration of energy metabolism is
      an essential hallmark of cancer. The role of altered energy metabolism in host
      cells in modulating latent and lytic EBV infection in NPC cells is unclear. In
      this review, we will discuss the impact of genetic alterations in NPC to module
      cellular metabolism and its influence on latent infection and lytic reactivation
      of EBV infection in NPC cells. In particular, the role of EBV-encoded genes in
      driving glucose metabolism and their contribution to NPC pathogenesis will be
      discussed. This new perspective on the interplay between EBV infection and
      altered host metabolic pathways in NPC pathogenesis may offer novel and effective
      therapeutic strategies in the treatment of NPC and other EBV-associated
      malignancies.

PMID- 29052134
TI  - Kaposi's Sarcoma-Associated Herpesvirus: Epidemiology and Molecular Biology.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also known as Human herpesvirus 8
      (HHV-8), is a member of the lymphotropic gammaherpesvirus subfamily and a human
      oncogenic virus. Since its discovery in AIDS-associated KS tissues by Drs. Yuan
      Chang and Patrick Moore, much progress has been made in the past two decades.
      There are four types of KS including classic KS, endemic KS, immunosuppressive
      therapy-related KS, and AIDS-associated KS. In addition to KS, KSHV is also
      involved in the development of primary effusion lymphoma (PEL) and certain types
      of multicentric Castleman's disease. KSHV manipulates numerous viral proteins to
      promote the progression of angiogenesis and tumorigenesis. In this chapter, we
      review the epidemiology and molecular biology of KSHV and the mechanisms
      underlying KSHV-induced diseases.

PMID- 29052135
TI  - Hepatitis C Virus-Associated Cancers.
AB  - Most hepatitis C virus (HCV) infection results in persistent infection.
      Significant portion of chronic HCV-infected patients develop hepatocellular
      carcinoma (HCC). Chronic hepatitis C is also associated with extrahepatic
      manifestations, including cryoglobulinemia, lymphoma, insulin resistance, type 2
      diabetes, and neurological disorders. The molecular mechanisms of how HCV
      infection causes liver cancer are largely unknown. HCV replication or viral
      proteins may perturb cellular hemostasis and induce the generation of reactive
      oxygen species (ROS); viral components or viral replication products act as
      agonist to trigger innate immune response and cause chronic inflammation. Within
      the liver, non-hepatocytes such as hepatic stellate cell (HSC) are activated upon
      HCV infection to provide the major source of extracellular proteins and play
      important roles in fibrogenesis. With the great achievements of HCV treatment,
      especially the direct-acting antivirals (DAAs) against HCV, HCV eradication is
      possible. However, until now there are only very limited data on the effect of
      DAA-based anti-HCV treatment on HCC patients.

PMID- 29052132
TI  - Current Progress in EBV-Associated B-Cell Lymphomas.
AB  - Epstein-Barr virus (EBV) was the first human tumor virus discovered more than 50
      years ago. EBV-associated lymphomagenesis is still a significant viral-associated
      disease as it involves a diverse range of pathologies, especially B-cell
      lymphomas. Recent development of high-throughput next-generation sequencing
      technologies and in vivo mouse models have significantly promoted our
      understanding of the fundamental molecular mechanisms which drive these cancers
      and allowed for the development of therapeutic intervention strategies. This
      review will highlight the current advances in EBV-associated B-cell lymphomas,
      focusing on transcriptional regulation, chromosome aberrations, in vivo studies
      of EBV-mediated lymphomagenesis, as well as the treatment strategies to target
      viral-associated lymphomas.

PMID- 29052136
TI  - Human T-Cell Leukemia Virus Type 1 Infection and Adult T-Cell Leukemia.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus discovered to
      cause adult T-cell leukemia (ATL), a highly aggressive blood cancer. HTLV-1
      research in the past 35 years has been most revealing in the mechanisms of viral
      oncogenesis. HTLV-1 establishes a lifelong persistent infection in CD4+ T
      lymphocytes. The infection outcome is governed by host immunity. ATL develops in
      2-5% of infected individuals 30-50 years after initial exposure. HTLV-1 encodes
      two oncoproteins Tax and HBZ, which are required for initiation of cellular
      transformation and maintenance of cell proliferation, respectively. HTLV-1
      oncogenesis is driven by a clonal selection and expansion process during which
      both host and viral factors cooperate to impair genome stability, immune
      surveillance, and other mechanisms of tumor suppression. A better understanding
      of HTLV-1 biology and leukemogenesis will reveal new strategies and modalities
      for ATL prevention and treatment.

PMID- 29052137
TI  - Malignancies in HIV-Infected and AIDS Patients.
AB  - Currently, HIV infection and AIDS are still one of the most important epidemic
      diseases around the world. As early in the initial stage of HIV epidemic, the
      high incidence of ADCs including Kaposi sarcoma and non-Hodgkin's lymphoma was
      the substantial amount of disease burden of HIV infection and AIDS. With the
      increasing accessibility of HAART and improving medical care for HIV infection
      and AIDS, AIDS-related illness including ADCs has dramatically decreased.
      Meanwhile, the incidence of NADCs rises in PLWH. Compared with the general
      population, most of cancers are more likely to attack PLWH, and NADCs in PLWH
      were characterized as earlier onset and more aggressive. However, the
      understanding for cancer development in PLWH is still dimness. Herein, we
      reviewed the current knowledge of epidemiology and pathogenesis for malignancies
      in PLWH summarized from recent studies. On the basis of that, we discussed the
      special considerations for cancer treatment in PLWH. As those malignancies could
      be the major issue for HIV infection or AIDS in the future, we expect enhanced
      investigations, surveillances, and clinical trial for improving the understanding
      and management for cancers developed in PLWH.

PMID- 29052138
TI  - Bacterial Infection and Associated Cancers.
AB  - Bacterial infections were traditionally not considered as major causes of cancer.
      However, increasing evidence in the past decades has suggested that several
      cancers are highly associated with bacterial infection. The bacterial infections
      have evolved some unique strategies including lateral gene transfer, biofilm and
      microbiome to induce genome instability and chronic inflammation, as well as
      escape of immune surveillance for carcinogenesis. Here we summarize and highlight
      the recent progress on understanding of how bacterial infection plays a role in
      tumor formation and malignancy.

PMID- 29052139
TI  - Parasite-Associated Cancers (Blood Flukes/Liver Flukes).
AB  - Parasitic infection remains as a persistent public health problem and can be
      carcinogenic. Three helminth parasites, namely, Clonorchis sinensis (liver fluke)
      and Opisthorchis viverrini as well as Schistosoma haematobium (blood fluke), are
      classified as Group 1 carcinogens by the World Health Organization's
      International Agency for Research on Cancer (IARC Infection with liver flukes
      (Opisthorchis viverrini, Opisthorchis felineus and Clonorchis sinensis), World
      Health Organization, International Agency for Research on Cancer, 2011).
      Infection by these parasites is frequently asymptomatic and is thus rarely
      diagnosed at early exposure. Persistent infection can cause severe cancer
      complications. Until now, the cellular and molecular mechanisms linking fluke
      infections to cancer formation have yet to be defined, although many studies have
      focused on these mechanisms in recent years, and numerous findings were made in
      various aspects of parasite-associated cancers. Herein, we only introduce the
      fluke-induced cholangiocarcinoma (CCA) and bladder carcinoma and mainly focus on
      key findings in the last 5 years.

PMID- 29052140
TI  - Prion Protein Family Contributes to Tumorigenesis via Multiple Pathways.
AB  - A wealth of evidence suggests that proteins from prion protein (PrP) family
      contribute to tumorigenesis in many types of cancers, including pancreatic ductal
      adenocarcinoma (PDAC), breast cancer, glioblastoma, colorectal cancer, gastric
      cancer, melanoma, etc. It is well documented that PrP is a biomarker for PDAC,
      breast cancer, and gastric cancer. However, the underlying mechanisms remain
      unclear. The major reasons for cancer cell-caused patient death are metastasis
      and multiple drug resistance, both of which connect to physiological functions of
      PrP expressing in cancer cells. PrP enhances tumorigenesis by multiple pathways.
      For example, PrP existed as pro-PrP in most of the PDAC cell lines, thus
      increasing cancer cell motility by binding to cytoskeletal protein filamin A
      (FLNa). Using PDAC cell lines BxPC-3 and AsPC-1 as model system, we identified
      that dysfunction of glycosylphosphatidylinositol (GPI) anchor synthesis machinery
      resulted in the biogenesis of pro-PrP. In addition, in cancer cells without FLNa
      expression, pro-PrP can modify cytoskeleton structure by affecting cofilin/F
      actin axis, thus influencing cancer cell movement. Besides pro-PrP, we showed
      that GPI-anchored unglycosylated PrP can elevate cell mobility by interacting
      with VEGFR2, thus stimulating cell migration under serum-free condition. Besides
      affecting cancer cell motility, overexpressed PrP or doppel (Dpl) in cancer cells
      has been shown to increase cell proliferation, multiple drug resistance, and
      angiogenesis, thus, proteins from PrP gene family by affecting important
      processes via multiple pathways for cancer cell growth exacerbating
      tumorigenesis.

PMID- 29052141
TI  - Murine Gammaherpesvirus 68: A Small Animal Model for Gammaherpesvirus-Associated
      Diseases.
AB  - Murine gammaherpesvirus 68 (MHV68) is a naturally occurring pathogen of murid
      rodents that is genetically related to the human gammaherpesviruses Epstein-Barr
      virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV). Viral, immunologic,
      and disease parameters following experimental infection of laboratory mice with
      MHV68 closely resemble what occurs during primary EBV infection of humans, which
      suggests that MHV68 infection of mice offers a small animal model to study in
      general the pathogenesis of gammaherpesvirus infections. Diseases elicited by
      MHV68 infection include lymphoproliferative diseases, idiopathic pulmonary
      fibrosis, and autoimmune diseases, ailments also associated with EBV infection of
      humans. Furthermore, MHV68 infection also is linked to the development of
      vasculitis, encephalomyelitis, and other disorders that resemble pathologies with
      viral and nonviral etiologies in humans. This review aims to provide an overview
      of MHV68-associated diseases in infected mice that may provide a model for
      understanding basic mechanisms by which similar diseases in humans occur and can
      be treated.

PMID- 29052142
TI  - Infection of KSHV and Interaction with HIV: The Bad Romance.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), namely, human herpesvirus 8 (HHV
      8), is considered as the pathogen of Kaposi's sarcoma (KS), the most frequent
      cancer in untreated HIV-infected individuals. Patients infected with HIV have a
      much higher possibility developing KS than average individual. Researchers have
      found that HIV, which functions as a cofactor of KS, contributes a lot to the
      development of KS. In this article, we will give a brief introduction of KS and
      KSHV and how the interaction between KSHV and HIV contributes to the development
      of KS. Also we will take a glance at the development of treatment in KS,
      especially AIDS-KS.

PMID- 29052143
TI  - Interplay Between Microenvironmental Abnormalities and Infectious Agents in
      Tumorigenesis.
AB  - Emerging evidence has shown that the cell of microenvironmental abnormalities is
      a key factor that controls many cellular physiological processes including
      cellular communication, homing, proliferation, and survival. Given its central
      regulatory role, it is therefore not surprising that it is widely exploited by
      infectious agents for inducing pathogenesis. In the past decade, a number of
      oncogenic pathogens including viruses, bacteria, and parasites are demonstrated
      to take advantage of the tumor microenvironmental factors including hypoxia,
      oxidative stress, and cytokines, to create an extracellular environment more
      favorable for pathogen survival and propagation and escape from the host immune
      surveillance. Here we summarize and highlight the current understanding of the
      interplay between common tumor microenvironmental factors and oncogenic pathogens
      in promoting tumorigenesis.

PMID- 29052144
TI  - The Effects of Extracellular Serum Concentration on APP Processing in Npc1
      Deficient APP-Overexpressing N2a Cells.
AB  - Amyloid precursor protein (APP) is cleaved by a set of proteases including alpha
      /beta-/gamma- and recently identified eta-secretases, generating C-terminal
      fragments (CTFs) of varying lengths and amyloid beta (Abeta) peptides, which are
      considered to play a pivotal role in Alzheimer's disease (AD) pathogenesis.
      Cellular cholesterol content/distribution can regulate the production/clearance
      of APP metabolites and hence modify AD pathology. To determine the functional
      relation between endosomal-lysosomal (EL) cholesterol sequestration and APP
      metabolism, we used our recently developed mouse N2a-ANPC cells that overexpress
      Swedish mutant human APP in the absence of cholesterol-trafficking Niemann-Pick
      type C1 (Npc1) protein. Here, we report that neither increased levels nor EL
      cholesterol sequestration altered APP holoprotein levels but caused the
      intracellular accumulation of APP alpha-/beta-/eta-CTFs and Abeta1-40/42
      peptides. The levels of APP-cleaved products increased as a function of
      extracellular serum concentration in N2a-ANPC cells, which are more vulnerable to
      death than the control cells. Additionally, we show that pH of the lysosomal
      vesicles in N2a-ANPC cells shifted to a less acidic range with increasing serum
      concentrations, thus making them less efficient functionally. Interestingly, the
      addition of cholesterol to the culture media not only increased the levels of
      cellular cholesterol and APP-cleaved products but also rendered the cells more
      vulnerable to toxicity. Collectively, our results suggest that extracellular
      cholesterol concentration in serum under conditions of Npc1 deficiency can
      influence intracellular cholesterol content/distribution and lysosomal efficacy,
      triggering the accumulation of toxic APP-cleaved products, eventually leading to
      cell death.

PMID- 29052146
TI  - Enzymatic activity induction of GST-family isoenzymes from pesticide mixture used
      in floriculture.
AB  - Glutathione S-transferases (GSTs) comprise a number of genes that codify for a
      group of isoenzymes that participate in phase II xenobiotic detoxification by
      means of conjugation with glutathione, producing hydrosoluble compounds. It has
      been demonstrated that some pesticides are substrates for GST isoenzymes.
      Floriculture is one of the main economic activities in the municipalities of
      Villa Guerrero and Atlacomulco; pesticides, applied as mixtures, are intensively
      used in this activity. In this study, total GST enzymatic activity and
      glutathione S-transferases theta 1 (GSTT1) enzymatic activity were calculated for
      a group of floriculture workers exposed to pesticides and for an unexposed group.
      The former comprised 169 floriculture workers, while the latter, 96 students. The
      value of the median GST enzymatic activity in the exposed group was 0.560 and
      0.169 MUmol/min/mL in the unexposed individuals. GSTT1 activity was 1.234
      MUmol/min/mL in the exposed group and 0.221 MUmol/min/mL in the unexposed group.
      Mann-Whitney U test showed a significant difference between these groups, for
      both total GST and GSTT1, p < 0.001. Our results show that exposure to pesticides
      increases the activities of total GST and GSTT1 enzymes.

PMID- 29052147
TI  - Pulsed light reduces the toxicity of the algal toxin okadaic acid to freshwater
      crustacean Daphnia pulex.
AB  - This constitutes the first study to report on the reduction in toxicity of the
      dinoflagellate algal toxin okadaic acid after novel pulsed light (PL) treatments
      where ecotoxicological assessment was performed using a miniaturised format of
      the conventional in vivo freshwater crustacean Daphnia sp. acute toxicity test.
      Bivalves accumulate this toxin, which can then enter the human food chain causing
      deleterious health effects such as diarrhetic shellfish poisoning. This
      miniaturised toxicological bioassay used substantially less sample volume and
      chemical reagents. Findings revealed a 24-h EC50 of 25.87 MUg/L for PL-treated
      okadaic acid at a UV dose of 12.98 MUJ/cm2 compared to a 24-h EC50 of 1.68 MUg/L
      for the untreated okadaic acid control, suggesting a 15-fold reduction in
      toxicity to Daphnia pulex. The bioassay was validated in this study and
      correlated well with the "classic" ISO format (r = 0.98) using the traditional
      reference chemical potassium dichromate (K2Cr2O7). Reduction by up to 65% in PL
      treated okadaic acid concentration was confirmed by LC-MS/MS analysis. Findings
      from this study have positive ecological, societal and enterprise implications,
      such as the development of PL technology for the prevention or reduce algal
      contamination of fisheries and aquaculture industries.

PMID- 29052148
TI  - Artificial 137Cs and natural 40K in mushrooms from the subalpine region of the
      Minya Konka summit and Yunnan Province in China.
AB  - A study on 137Cs pollution and activity concentrations of 40K in mushrooms of the
      genera Cortinarius, Leccinum, Russula, Tricholoma, Tylopilus, and Xerocomus from
      two neighboring regions in southwest China in 2010-2013 revealed different
      patterns of pollution with 137Cs, which seemed to be highly dependent on climate
      conditions. Tricholoma matsutake was collected in Yunnan before and after the
      Fukushima Dai-ichi nuclear accident and showed similar contamination with 137Cs.
      Mushrooms from the elevation of 2800-3480 m above sea level on the east slope of
      Minya Konka and forest topsoil showed higher contamination with 137Cs than
      mushrooms from the highlands of Yunnan. In detail, the activity concentration of
      137Cs in caps of mushrooms from Minya Konka were in the range 62 +/- 6-280 +/-
      150 Bq kg-1 dry biomass and from Yunnan at < 4.4-83 +/- 3 Bq kg-1 dry biomass.
      The climate in the region of the Minya Konka is much colder than in Yunnan, which
      seems to favor deposition of 137Cs at higher altitudes from global atmospheric
      circulation. The activity concentration of 40K in mushrooms and soils highly
      exceeded that of 137Cs. The assessed annual effective doses for 137Cs in 1 kg of
      consumed mushrooms of the genera Leccinum and Xerocomus in Yunnan were low, i.e.,
      in the range < 0.0043-0.049 +/- 0.004 MUSv, while those for 40K were 0.26 +/-
      0.02-0.81 +/- 0.09 MUSv.

PMID- 29052149
TI  - Rare-earth elements in human colostrum milk.
AB  - Rare-earth elements (REEs) are used in a growing number of applications, and
      their release to environment has increased over the decades. Knowledge of REEs in
      human milk and factors that could possibly influence their concentration is
      scarce. This study evaluated the concentrations of 16 REEs (Ce, Eu, Er, Gd, La,
      Nd, Pr, Sc, Sm, Dy, Ho, Lu, Tb, Tm, Y, and Yb) in human colostrum milk collected
      from Polish women (n = 100) with the ICP-OES technique. The concentrations (mean
      +/- SD) of Pr (41.9 +/- 13.2 MUg L-1), Nd (11.0 +/- 4.0 MUg L-1), La (7.1 +/- 5.2
      MUg L-1), and Er (2.2 +/- 0.8 MUg L-1) were found above detection limits. The
      total mean +/- SD concentration of detected REEs was 60.9 +/- 17.8 MUg L-1.
      Current smokers displayed significantly increased Nd concentrations compared to
      women who had never smoked. No other associations between REEs in colostrum milk
      and age, diet in pregnancy (food supplement use and frequency of fish, meat, and
      vegetable consumption) or place of living (urban/rural) were found. This study
      adds to general understanding of the occurrence and turnover of REEs in women and
      human fluids.

PMID- 29052145
TI  - Cell Death Pathways: a Novel Therapeutic Approach for Neuroscientists.
AB  - In the first part, the following mechanisms involved in different forms of cell
      death are considered, with a view to identifying potential therapeutic targets:
      tumour necrosis factor receptors (TNFRs) and their engagement by tumour necrosis
      factor-alpha (TNF-alpha); poly [ADP-ribose] polymerase (PARP)-1 cleavage; the
      apoptosis signalling kinase (ASK)-c-Jun N-terminal kinase (JNK) axis; lysosomal
      permeability; activation of programmed necrotic cell death; oxidative stress,
      caspase-3 inhibition and parthanatos; activation of inflammasomes by reactive
      oxygen species and the development of pyroptosis; oxidative stress, calcium
      dyshomeostasis and iron in the development of lysosomal-mediated necrosis and
      lysosomal membrane permeability; and oxidative stress, lipid peroxidation, iron
      dyshomeostasis and ferroptosis. In the second part, there is a consideration of
      the role of lethal and sub-lethal activation of these pathways in the
      pathogenesis and pathophysiology of neurodegenerative and neuroprogressive
      disorders, with particular reference to the TNF-alpha-TNFR signalling axis;
      dysregulation of ASK-1-JNK signalling; prolonged or chronic PARP-1 activation;
      the role of pyroptosis and chronic inflammasome activation; and the roles of
      lysosomal permeabilisation, necroptosis and ferroptosis. Finally, it is suggested
      that, in addition to targeting oxidative stress and inflammatory processes
      generally, neuropsychiatric disorders may respond to therapeutic targeting of TNF
      alpha, PARP-1, the Nod-like receptor NLRP3 inflammasome and the necrosomal
      molecular switch receptor-interacting protein kinase-3, since their widespread
      activation can drive and/or exacerbate peripheral inflammation and
      neuroinflammation even in the absence of cell death. To this end, the use is
      proposed of a combination of the tetracycline derivative minocycline and N
      acetylcysteine as adjunctive treatment for a range of neuropsychiatric disorders.

PMID- 29052150
TI  - Effective removal of ammonia nitrogen from waste seawater using crystal seed
      enhanced struvite precipitation technology with response surface methodology for
      process optimization.
AB  - Traditional biological treatment was not effective for removing nitrogen from
      saline wastewater due to the inhibition of high salinity on biomass activity. In
      this context, a method of removing ammonia nitrogen from waste seawater was
      proposed by struvite precipitation which was enhanced by seeding technique. The
      abundant magnesium contained in waste seawater was used as the key component of
      struvite crystallization without additional magnesium. The effects of pH and P:N
      molar ratio on ammonia nitrogen removal efficiency were studied. The results
      showed that optimum pH value was in range of 8.5-10 and the P:N molar ratio
      should be controlled within 2:1-3:1. XRD and SEM-EDS analyses of the precipitates
      proved that Ca2+ and excess Mg2+ contained in waste seawater inhibited the
      struvite crystallization by competing PO43- to form by-products. Then, seeding
      technique for enhancing the struvite crystallization was investigated, and the
      results indicated that using preformed struvite as crystal seed significantly
      improved the ammonia nitrogen removal efficiency, especially when initial ammonia
      nitrogen concentration was relatively low. Moreover, response surface
      optimization experiment following a Box-Behnken design was conducted. A response
      surface model was established, based on which optimum process conditions were
      determined and interactions between various factors were clarified. At last,
      economic evaluation demonstrated this proposed method was economic feasible.

PMID- 29052152
TI  - A New Understanding of Quality of Life in Children and Adolescents with Obesity:
      Contribution of the Self-determination Theory.
AB  - PURPOSE OF REVIEW: Preservation of Quality of Life (QOL) is now a major
      determinant of obesity management, but little is known about variables predicting
      QOL. Identifying these predicting variables of QOL would provide further
      understanding of the QOL concept and help draw clinical implications. The Self
      determination Theory (SDT) is a promising understanding perspective of the QOL.
      RECENT FINDINGS: The SDT postulates that well-being and motivation are determined
      by the satisfaction of three needs: autonomy, competence, and relatedness. Many
      researches have confirmed the relationships between these SDT's needs and well
      being, but this theory has little been applied to the problem of QOL in obese
      children and adolescents. Literature results and theoretical implications of the
      SDT in understanding of QOL in youth obesity are discussed. New clinical
      applications could be drawn: in children with obesity, interventions promoting
      high satisfaction of the SDT's needs could improve their QOL and help them break
      the vicious circles of overweight.

PMID- 29052151
TI  - Hair mercury and risk assessment for consumption of contaminated seafood in
      residents from the coast of the Persian Gulf, Iran.
AB  - The health risks of mercury exposure due to the high consumption of aquatic were
      assessed for fishermen and non-fishermen families living on the Bandar Abbas,
      Bushehr, and Mahshahr cities located in the coast of Persian Gulf (Iran). The
      mean hair mercury concentration of people in Bandar Abbas, Bushehr, and Mahshahr
      cities was obtained 1.56 +/- 0.17, 1.97 +/- 0.22, and 5.12 +/- 0.3 MUg g-1,
      respectively. Hair mercury concentration in 8.8% of people exceeded the no
      observed adverse effects level (NOAEL) of 10 MUg g-1 declared by the World Health
      Organization (WHO). The fish and shrimps consumption, place of living, and fisher
      and non-fisherman family were variables that significantly effected on mercury
      levels in the hair. The effect of other factors (age, sex, and number of dental
      amalgam fillings) on hair mercury was not significant. The mean concentrations of
      mercury in three fish species in Mahshahr exceeded the recommended maximum
      standard level (0.5 MUg g-1) set by the Joint Food and Agriculture
      Organization/World Health Organization Expert Committee on Food Additives
      (JECFA). The estimated weekly intake (EWI) for mercury in some fish species in
      Bandar Abbas, Bushehr, and Mahshahr was higher than the provisional tolerable
      weekly intake (1.6 MUg kg-1 bw) set by European Food Safety Authority (EFSA) for
      some groups. The significant positive correlation between daily mercury intake
      and hair mercury concentration of people (r = 0.64, P < 0.001) reasserts that the
      hair mercury concentration could be explained by fish consumption. HQ > 1 was
      obtained for women in child bearing age in fishermen families in Bandar Abbas and
      Bushehr cities, children in fishermen families in Bushehr, and for all groups of
      population except adult in non-fishermen families in Mahshahr. So, the limited
      consumption of some fish species for these groups of people is recommended. The
      maximum of allowable fish consumption rate was 0.70 meals/month for Pseudorhombus
      arsius from Mahshahr fish for women of child bearing age. Also, it is necessary
      to create and monitor and enforce environmental standards, preventing the entry
      of pollutants released into the marine aquatic environment without proper early
      treatment.

PMID- 29052154
TI  - Heath State Utility Values for Cost-Effectiveness Models.

PMID- 29052155
TI  - Special Edition on Utility Measurement, PharmacoEconomics.

PMID- 29052153
TI  - Food for Thought: Reward Mechanisms and Hedonic Overeating in Obesity.
AB  - PURPOSE OF REVIEW: This review examines the food addiction model and the role of
      food hedonic pathways in the pathogenesis and treatment of obesity. RECENT
      FINDINGS: The hedonic pathway interacts with the obesogenic environment to
      override homeostatic mechanisms to cause increase in body weight. Weight gain
      sustained over time leads to "upward setting" of defended level of body-fat mass.
      There are neurobiological and phenotypic similarities and differences between
      hedonic pathways triggered by food compared with other addictive substances, and
      the entity of food addiction remains controversial. Treatment for obesity
      including pharmacotherapy and bariatric surgery impacts on neural pathways
      governing appetite and hedonic control of food intake. The food addiction model
      may also have significant impact on public health policy, regulation of certain
      foods, and weight stigma and bias. Recent rapid progress in delineation of food
      hedonic pathways advances our understanding of obesity and facilitates
      development of effective treatment measures against the disease.

PMID- 29052156
TI  - The Identification, Review and Synthesis of Health State Utility Values from the
      Literature.
AB  - Systematic literature reviews of health-related quality of life (HRQoL) evidence
      that are to inform economic models can be challenging due to the volume of hits
      identified in searches using generic terms for HRQoL. Nevertheless, a robust
      review of the literature is required to ensure that the health state utility
      values (HSUVs) used in the economic model are the most appropriate available.
      This article provides a synopsis of literature relating to identifying, reviewing
      and synthesising HSUVs. The process begins with scoping the needs of the economic
      model, including the definitions of health states and the requirements of any
      reimbursement agencies. A sequence of searches may be required as the economic
      model evolves. The terminology used for HRQoL measures may be problematic, and as
      there is no robust HRQoL filter [equivalent to that applied for randomised
      control trial (RCTs)], sifting the results of sensitive searches can be resource
      intensive. Alternative approaches such as forward and backward citation searches
      may reduce the resources required, while maintaining the integrity of the search.
      Any included studies should be assessed in terms of quality using a recommended
      checklist, and insufficient detail in the primary studies should be noted as a
      short-coming in this exercise. Subject to homogeneity (similar populations, same
      measure and preference weights) evidence can be pooled in some way, although
      methodological research into the appropriateness of alternative techniques for
      meta-analysis is in its infancy. Reporting standards are key and as a minimum
      should include details on searches, inclusion/exclusion criteria (together with
      rationale for exclusion at each stage), assessment of quality and relevance of
      included studies, and justification for the choice of final HSUVs.

PMID- 29052157
TI  - A Review of Generic Preference-Based Measures for Use in Cost-Effectiveness
      Models.
AB  - Generic preference-based measures (GPBMs) of health are used to obtain the
      quality adjustment weight required to calculate the quality-adjusted life year in
      health economic models. GPBMs have been developed to use across different
      interventions and medical conditions and typically consist of a self-complete
      patient questionnaire, a health state classification system, and preference
      weights for all states defined by the classification system. Of the six main
      GPBMs, the three most frequently used are the Health Utilities Index version 3,
      the EuroQol 5 dimensions (3 and 5 levels), and the Short Form 6 dimensions. There
      are considerable differences in GPBMs in terms of the content and size of
      descriptive systems (i.e. the numbers of dimensions of health and levels of
      severity within these), the methods of valuation [e.g. time trade-off (TTO),
      standard gamble (SG)], and the populations (e.g. general population, patients)
      used to value the health states within the descriptive systems. Although GPBMs
      are anchored at 1 (full health) and 0 (dead), they produce different health state
      utility values when completed by the same patient. Considerations when selecting
      a measure for use in a clinical trial include practicality, reliability, validity
      and responsiveness. Requirements of reimbursement agencies may impose additional
      restrictions on suitable measures for use in economic evaluations, such as the
      valuation technique (TTO, SG) or the source of values (general public vs.
      patients).

PMID- 29052158
TI  - Estimating Health State Utility Values for Comorbidities.
AB  - A comorbidity is defined as the presence of at least one additional health
      condition co-occurring with a primary health condition. Decision analytic models
      in healthcare depict the typical clinical pathway of patients in general clinical
      practice and frequently include health states defined to represent comorbidities
      such as sequelae or adverse events. Health state utility values (HSUVs) are often
      not available for these and analysts generally estimate them. This article
      provides a summary of the methodological literature on estimating methods
      frequently used together with worked examples. The three main methods used
      (minimum, multiplicative and additive) can produce a wide range in the values
      estimated. In general, the minimum method overestimates observed HSUVs and the
      magnitude of error tends to increase as the observed values decrease. Conversely,
      the additive and multiplicative methods generally underestimate observed values
      and the magnitude of the errors is generally greater for the additive method.
      HSUVs estimated using the multiplicative method tend to decrease for lower HSUVs
      and the largest errors are in observed HSUVs >0.6. Differences in estimated
      values can produce substantial differences in the resulting incremental cost
      effectiveness ratio. Based on the current evidence, the multiplicative method is
      advocated but additional research is required to determine appropriate methods
      when estimating values for additional comorbidities.

PMID- 29052159
TI  - Recommended Methods for the Collection of Health State Utility Value Evidence in
      Clinical Studies.
AB  - A conceptual model framework and an initial literature review are invaluable when
      considering what health state utility values (HSUVs) are required to populate
      health states in decision models. They are the recommended starting point early
      within a research and development programme, and before development of phase III
      trial protocols. While clinical trials can provide an opportunity to collect the
      required evidence, their appropriateness should be reviewed against the
      requirements of the model structure taking into account population
      characteristics, time horizon and frequency of clinical events. Alternative
      sources such as observational studies or registries may be more appropriate when
      evidence describing changes in HSUVs over time or rare clinical events is
      required. Phase IV clinical studies may provide the opportunity to collect
      additional longitudinal real-world evidence. Aspects to consider when designing
      the collection of the evidence include patient and investigator burden, whom to
      ask, the representativeness of the population, the exact definitions of health
      states within the economic model, the timing of data collection, sample size, and
      mode of administration. Missing data can be an issue, particularly in
      longitudinal studies, and it is important to determine whether the missing data
      will bias inferences from analyses. For example, respondents may fail to complete
      follow-up questionnaires because of a relapse or the severity of their condition.
      The decision on the preferred study type and the particular quality of life
      measure should be informed by any evidence currently available in the literature,
      the design of data collection, and the exact requirements of the model that will
      be used to support resource allocation decisions (e.g. reimbursement).

PMID- 29052160
TI  - The Use of Mapping to Estimate Health State Utility Values.
AB  - Mapping functions are estimated using regression analyses and are frequently used
      to predict health state utility values (HSUVs) in decision analytic models.
      Mapping functions are used when evidence on the required preference-based measure
      (PBM) is not available, or where modelled values are required for a decision
      analytic model, for example to control for important sociodemographic variables
      (such as age or gender). This article provides an overview of the latest
      recommendations including pre-mapping considerations, the mapping process
      including data requirements for undertaking the estimation of mapping functions,
      regression models for estimating mapping functions, assessing performance and
      reporting standards for mapping studies. Examples in rheumatoid arthritis are
      used for illustration. When reporting the results of mapping standards the
      following should be reported: a description of the dataset used (including
      distributions of variables used) and any analysis used to inform the selection of
      the model type and model specification. The regression method and specification
      should be justified, and as summary statistics may mask systematic bias in
      errors, plots comparing observed and predicted HSUVs. The final model
      (coefficients, error term(s), variance and covariance) should be reported
      together with a worked example. It is important to ensure that good practice is
      followed as any mapping functions will only be as appropriate and accurate as the
      method used to obtain them; for example, mapping should not be used if there is
      no overlap between the explanatory and target variables.

PMID- 29052161
TI  - Sourcing and Using Appropriate Health State Utility Values in Economic Models in
      Health Care.

PMID- 29052162
TI  - International Regulations and Recommendations for Utility Data for Health
      Technology Assessment.
AB  - Recommendations and guidelines for the collection, generation, source and usage
      of utility data for health technology assessment (HTA) vary across different
      countries, with no international consensus. Many international agencies generate
      their own guidelines providing details on their preferred methods for HTA
      submissions, and there is variability in both what they recommend and the clarity
      and amount of detail provided in their guidelines. This article provides an
      overview of international regulations and recommendations for utility data in HTA
      for a selection of key HTA countries: Australia, Canada, France, Germany, the
      Netherlands, Spain (Catalonia), Sweden and the UK (England/Wales and Scotland).
      International guidelines are typically clear and detailed for the selection of
      countries assessed regarding the source description of health states (e.g.
      generic preference-based measure) and who should provide preference weights for
      these health states (e.g. general population for own country). Many guidelines
      specify the use of off-the-shelf generic preference-based measures, and some
      further specify a measure, such as EQ-5D. However, international guidelines are
      either unclear or lack detailed guidance regarding the collection (e.g. patients
      report own health), source (e.g. clinical trial) and usage (e.g. adjusting for
      comorbidities) of utility values. It is argued that there is a need for
      transparent and detailed international guidelines on utility data recommendations
      to provide decision makers with the best possible evidence. Where this is not
      possible it is recommended that best practice should be used to inform the
      collection, source and usage of utility values in HTA.

PMID- 29052163
TI  - The Use of Health State Utility Values in Decision Models.
AB  - Methodological issues of how to use health state utility values (HSUVs) in
      decision models arise frequently, including the most appropriate evidence to use
      as the baseline (e.g. the baseline HSUVs associated with avoiding a particular
      health condition or event), how to capture changes due to adverse events and how
      to appropriately capture uncertainty in progressive conditions where the expected
      change in quality of life is likely to be monotonically decreasing over time. As
      preference-based measures provide different values when collected from the same
      patient, it is important to ensure that all HSUVs used within a single model are
      obtained from the same instrument where ever possible. When people enter the
      model without the condition of interest (e.g. primary prevention of
      cardiovascular disease, screening or vaccination programmes), appropriate age-
      and gender-adjusted HSUVs from people without the particular condition should be
      used as the baseline. General population norms may be used as a proxy if the
      exact condition-specific evidence is not available. Individual discrete health
      states should be used for serious adverse reactions to treatment and the
      corresponding HSUVs sourced as normal. Care should be taken to avoid double
      counting when capturing the effects for both less severe adverse reactions (e.g.
      itchy skin rash or dry cough) and more severe adverse events (e.g. fatigue in
      oncology). Transparency in reporting standards for both the justification of the
      evidence used and any 'adjustments' is important to increase readers' confidence
      that the evidence used is the most appropriate available.

PMID- 29052165
TI  - A methodological review of meta-analyses of the effectiveness of clinical
      psychology treatments.
AB  - This article presents a methodological review of 54 meta-analyses of the
      effectiveness of clinical psychological treatments, using standardized mean
      differences as the effect size index. We statistically analyzed the distribution
      of the number of studies of the meta-analyses, the distribution of the sample
      sizes in the studies of each meta-analysis, the distribution of the effect sizes
      in each of the meta-analyses, the distribution of the between-studies variance
      values, and the Pearson correlations between effect size and sample size in each
      meta-analysis. The results are presented as a function of the type of
      standardized mean difference: posttest standardized mean difference, standardized
      mean change from pretest to posttest, and standardized mean change difference
      between groups. These findings will help researchers design future Monte Carlo
      and theoretical studies on the performance of meta-analytic procedures, based on
      the manipulation of realistic model assumptions and parameters of the meta
      analyses. Furthermore, the analysis of the distribution of the mean effect sizes
      through the meta-analyses provides a specific guide for the interpretation of the
      clinical significance of the different types of standardized mean differences
      within the field of the evaluation of clinical psychological interventions.

PMID- 29052164
TI  - The Role of Condition-Specific Preference-Based Measures in Health Technology
      Assessment.
AB  - A condition-specific preference-based measure (CSPBM) is a measure of health
      related quality of life (HRQOL) that is specific to a certain condition or
      disease and that can be used to obtain the quality adjustment weight of the
      quality-adjusted life-year (QALY) for use in economic models. This article
      provides an overview of the role and the development of CSPBMs, and presents a
      description of existing CSPBMs in the literature. The article also provides an
      overview of the psychometric properties of CSPBMs in comparison with generic
      preference-based measures (generic PBMs), and considers the advantages and
      disadvantages of CSPBMs in comparison with generic PBMs. CSPBMs typically include
      dimensions that are important for that condition but may not be important across
      all patient groups. There are a large number of CSPBMs across a wide range of
      conditions, and these vary from covering a wide range of dimensions to more
      symptomatic or uni-dimensional measures. Psychometric evidence is limited but
      suggests that CSPBMs offer an advantage in more accurate measurement of milder
      health states. The mean change and standard deviation can differ for CSPBMs and
      generic PBMs, and this may impact on incremental cost-effectiveness ratios.
      CSPBMs have a useful role in HTA where a generic PBM is not appropriate,
      sensitive or responsive. However, due to issues of comparability across different
      patient groups and interventions, their usage in health technology assessment is
      often limited to conditions where it is inappropriate to use a generic PBM or
      sensitivity analyses.

PMID- 29052166
TI  - Is human classification by experienced untrained observers a gold standard in
      fixation detection?
AB  - Manual classification is still a common method to evaluate event detection
      algorithms. The procedure is often as follows: Two or three human coders and the
      algorithm classify a significant quantity of data. In the gold standard approach,
      deviations from the human classifications are considered to be due to mistakes of
      the algorithm. However, little is known about human classification in eye
      tracking. To what extent do the classifications from a larger group of human
      coders agree? Twelve experienced but untrained human coders classified fixations
      in 6 min of adult and infant eye-tracking data. When using the sample-based
      Cohen's kappa, the classifications of the humans agreed near perfectly. However,
      we found substantial differences between the classifications when we examined
      fixation duration and number of fixations. We hypothesized that the human coders
      applied different (implicit) thresholds and selection rules. Indeed, when
      spatially close fixations were merged, most of the classification differences
      disappeared. On the basis of the nature of these intercoder differences, we
      concluded that fixation classification by experienced untrained human coders is
      not a gold standard. To bridge the gap between agreement measures (e.g., Cohen's
      kappa) and eye movement parameters (fixation duration, number of fixations), we
      suggest the use of the event-based F1 score and two new measures: the relative
      timing offset (RTO) and the relative timing deviation (RTD).

PMID- 29052167
TI  - The Evaluative Lexicon 2.0: The measurement of emotionality, extremity, and
      valence in language.
AB  - The rapid expansion of the Internet and the availability of vast repositories of
      natural text provide researchers with the immense opportunity to study human
      reactions, opinions, and behavior on a massive scale. To help researchers take
      advantage of this new frontier, the present work introduces and validates the
      Evaluative Lexicon 2.0 (EL 2.0)-a quantitative linguistic tool that specializes
      in the measurement of the emotionality of individuals' evaluations in text.
      Specifically, the EL 2.0 utilizes natural language to measure the emotionality,
      extremity, and valence of evaluative reactions and attitudes. The present article
      describes how we used a combination of 9 million real-world online reviews and
      over 1,500 participant judges to construct the EL 2.0 and an additional 5.7
      million reviews to validate it. To assess its unique value, the EL 2.0 is
      compared with two other prominent text analysis tools-LIWC and Warriner et al.'s
      (Behavior Research Methods, 45, 1191-1207, 2013) wordlist. The EL 2.0 is
      comparatively distinct in its ability to measure emotionality and explains a
      significantly greater proportion of the variance in individuals' evaluations. The
      EL 2.0 can be used with any data that involve speech or writing and provides
      researchers with the opportunity to capture evaluative reactions both in the
      laboratory and "in the wild." The EL 2.0 wordlist and normative emotionality,
      extremity, and valence ratings are freely available from
      www.evaluativelexicon.com .

PMID- 29052168
TI  - Normative ratings for perceptual and motor attributes of 750 object concepts in
      Spanish.
AB  - Subjective ratings of perceptual and motor attributes were obtained for a set of
      750 concrete concepts in Spanish by requiring scale-based judgments from a sample
      of university students (N = 539). Following on the work of Amsel, Urbach, and
      Kutas (2012), the seven attributes were color, motion, sound, smell, taste,
      graspability, and pain. Normative data based on the obtained ratings are provided
      as a tool for future investigations. Additionally, the relationships of these
      attributes to other lexical dimensions (e.g., familiarity, frequency,
      concreteness) and the factorial organization of concepts around the main
      components were analyzed. The pattern of results is consistent with prior
      findings that highlight the relevance of dimensions related to survival as being
      crucially involved in conceptual processing.

PMID- 29052169
TI  - Once more with feeling: Normative data for the aha experience in insight and
      noninsight problems.
AB  - Despite the presumed ability of insight problems to elicit the subjective feeling
      of insight, as well as the use of so-called insight problems to investigate this
      phenomenon for over 100 years, no research has collected normative data regarding
      the ability of insight problems to actually elicit the feeling of insight in a
      given individual. The work described in this article provides an overview of both
      classic and contemporary problems used to examine the construct of insight and
      presents normative data on the success rate, mean time to solution, and mean
      rating of aha experience for each problem and task type. We suggest using these
      data in future work as a reference for selecting problems on the basis of their
      ability to elicit an aha experience.

PMID- 29052170
TI  - The histopathological evaluation of small fiber neuropathy in patients with
      vitamin B12 deficiency.
AB  - Small fiber neuropathy (SFN), due to loss of A-delta and unmyelinated C fibers,
      is a cause of neuropathic pain. Although the patients with vitamin B12 deficiency
      are included in SFN studies in the literature, there is no histopathological
      study investigating the small fiber loss solely in patients with vitamin B12
      deficiency. In this pilot study, we aim to demonstrate the intraepidermal nerve
      fiber density (IENFD) in skin punch biopsy of patients with vitamin B12
      deficiency. Ten patients with vitamin B12 deficiency suffering from neuropathic
      pain and as control group ten patients with vitamin B12 deficiency without
      neuropathic pain were included. Neurological examination, electrophysiological
      evaluation, and DN4 questionnaire were performed. Subsequently, skin punch biopsy
      10 cm above the lateral malleolus was done. The biopsy samples were stained with
      PGP9.5 antibody, and IENFD was determined. IENFD was low in two groups compared
      to their age normative values. The median of IENFD was 3.345 (1.12-5.32) in
      patients with neuropathic pain and 6. 20 (4.6-9.8) in controls (p < 0.001). Our
      pilot study showed that vitamin B12 deficiency causes symptomatic as well as
      asymptomatic small fiber loss like diabetes mellitus.

PMID- 29052171
TI  - Statin Use and Breast Cancer Prognosis in Black and White Women.
AB  - Studies show decreased risk of breast cancer recurrence and improved survival
      with statin use, but data on racial disparities regarding breast cancer prognosis
      and statin use are lacking. Our objective was to investigate if racial
      disparities in breast cancer prognosis can be partially explained by differences
      in pre-diagnosis statin use. Patients were identified from a prospective,
      multicenter study examining the effects of metabolic factors on breast cancer
      prognosis in Black and White women. Statin use, prognosis (as measured by
      Nottingham Prognostic Index), anthropometric, tumor, and socio-demographic
      characteristics were examined. Five hundred eighty-seven women (487 White, 100
      Black) with newly diagnosed primary invasive breast cancer were recruited.
      Obesity was more prevalent in Black women than White women (47 vs 19%, p < 0.01);
      both groups had similar low-density lipoprotein (LDL) cholesterol levels (113 +/-
      41 vs 113 +/- 36 mg/dl, p = 0.90). More Black women used statins than White women
      (18 vs 11%, p = 0.06). Black women had a worse prognosis in an adjusted model
      than White women (OR 2.13 95% CI 1.23-3.67). Statin use was not associated with
      prognosis in unadjusted (OR 1.03, 95% CI 0.53-2.0) and adjusted models (OR 1.14,
      95% CI 0.56-2.31). In women with newly diagnosed breast cancer, Black women were
      more likely to be treated with statins than White women, contrary to previous
      studies. Black women had worse prognosis than White women, but this difference
      was not explained by differences in pre-diagnosis statin use. Our study suggests
      that differences in pre-diagnosis statin use do not contribute to racial
      disparities in breast cancer prognosis.

PMID- 29052173
TI  - Regulation of Osteoblast Differentiation and Iron Content in MC3T3-E1 Cells by
      Static Magnetic Field with Different Intensities.
AB  - Many studies have indicated that static magnetic fields (SMFs) have positive
      effects on bone tissue, including bone formation and bone healing process.
      Evaluating the effects of SMFs on bone cell (especially osteoblast) function and
      exploring the mechanism, which is critical for understanding the possible risks
      or benefits from SMFs to the balance of bone remodeling. Iron and magnetic fields
      have the natural relationship, and iron is an essential element for normal bone
      metabolism. Iron overload or deficiency can cause severe bone disorders including
      osteoporosis. However, there are few reports regarding the role of iron in the
      regulation of bone formation under SMFs. In this study, hypomagnetic field (HyMF)
      of 500 nT, moderate SMF (MMF) of 0.2 T, and high SMF (HiMF) of 16 T were used to
      investigate how osteoblast (MC3T3-E1) responses to SMFs and iron metabolism of
      osteoblast under SMFs. The results showed that SMFs did not pose severe toxic
      effects on osteoblast growth. During cell proliferation, iron content of
      osteoblast MC3T3-E1 cells was decreased in HyMF, but was increased in MMF and
      HiMF after exposure for 48 h. Compared to untreated control (i.e., geomagnetic
      field, GMF), HyMF and MMF exerted deleterious effects on osteoblast
      differentiation by simultaneously retarding alkaline phosphatase (ALP) activity,
      mineralization and calcium deposition. However, when exposed to HiMF of 16 T, the
      differentiation potential showed the opposite tendency with enhanced
      mineralization. Iron level was increased in HyMF, constant in MMF and decreased
      in HiMF during cell differentiation. In addition, the mRNA expression of
      transferrin receptor 1 (TFR1) was promoted by HyMF but was inhibited by HiMF. At
      the same time, HiMF of 16 T and MMF of 0.2 T increased the expression of
      ferroportin 1 (FPN1). In conclusion, these results indicated that osteoblast
      differentiation can be regulated by altering the strength of the SMF, and iron is
      possibly involved in this process.

PMID- 29052174
TI  - Phagocytosis Deficiency of Macrophages in NOD.H-2h4 Mice Accelerates the Severity
      of Iodine-Induced Autoimmune Thyroiditis.
AB  - Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte
      apoptosis and increases the incidence and prevalence of autoimmune thyroiditis
      (AIT). However, the sequence of events between the appearance of thyrocyte
      apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore,
      few studies have investigated the role of macrophage phagocytosis in the
      development of AIT. Therefore, we evaluated the relationship between apoptosis
      and inflammatory infiltration in NOD.H-2h4 mouse thyroids by comparing the
      sequence of events in tissue samples. We also investigated the role of
      macrophages by comparing macrophage phagocytosis function in BALB/c, C57BL/6, and
      NOD.H-2h4 mice treated with different levels of iodine. Terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assays and thyroid inflammatory scores
      revealed that apoptosis (2 weeks) occurred before inflammatory infiltration (4
      weeks). Phosphatidylserine (PS) expression on the extracellular surface of the
      cell membrane and double-stranded DNA fragments associated with apoptosis
      appeared at 2 and 8 weeks, respectively. Additionally, although apoptosis was
      enhanced in the thyroids of mice supplemented with excess iodine (0.05 +/- 0.12
      vs 1.63 +/- 0.82% for BALB/c, 0.09 +/- 0.14 vs 1.51 +/- 0.34% for C57BL/6, and
      0.07 +/- 1.11 vs 4.72 +/- 0.62% for NOD.H-2h4 mice), only NOD.H-2h4 mouse
      thyroids presented with inflammation. Furthermore, macrophages from NOD.H-2h4
      mice (44.46 +/- 1.79%) exhibited decreased phagocytotic activity relative to that
      in BALB/c (54.21 +/- 4.58%) and C57BL/6 (58.96 +/- 4.04%) mice. There were no
      differences in phagocytosis function between NOD.H-2h4 mice supplemented with
      excess iodine or left untreated (24.50 +/- 2.66 vs 21.71 +/- 1.79%, p = 0.06). In
      conclusion, deficiencies in the apoptosis clearance of macrophages in NOD.H-2h4
      mice may constitute an early pathogenic mechanism in AIT that is not influenced
      by iodine intake.

PMID- 29052175
TI  - African-Americans with Cirrhosis Are Less Likely to Receive Endoscopic Variceal
      Screening Within One Year of Cirrhosis Diagnosis.
AB  - BACKGROUND: Esophageal variceal hemorrhage is a complication of cirrhosis that
      carries high mortality, and can be reduced with timely endoscopic variceal
      screening and treatment. AIM: We aim to evaluate overall rates of and disparities
      in receipt of endoscopic variceal screening among an ethnically diverse urban
      safety-net hospital. METHODS: All consecutive adults with cirrhosis (7/1/2014 to
      12/31/2015) were retrospectively evaluated to determine the rates of receiving
      esophageal variceal screening within 6 months and within 1 year after cirrhosis
      diagnosis. Race-/ethnicity-specific differences in rates of variceal screening
      were compared using chi-square testing and multivariate regression methods.
      RESULTS: Among 157 patients (65% male, 33.8% Hispanic, 22.3% African-American,
      44.6% alcoholic liver disease, 29.9% chronic HCV), 56.8% received variceal
      screening within 6 months and 65.8% received screening within 1 year. Compared to
      non-Hispanic whites with cirrhosis, African-Americans (52.2 vs. 76.2%, p < 0.05),
      Asians (57.1 vs. 76.2%, p < 0.05), and Hispanics (43.9 vs. 76.2%, p < 0.05) were
      all significantly less likely to receive endoscopic variceal screening within 6
      months after cirrhosis diagnosis. On multivariate analysis, African-Americans
      with cirrhosis were 66% less likely to receive variceal screening compared to non
      Hispanic whites (HR 0.34, 95% CI 0.15-0.77, p < 0.01). CONCLUSION: Among adults
      with cirrhosis at a community-based safety-net hospital system, overall first
      time variceal screening remains suboptimal. African-Americans were the least
      likely to receive timely variceal screening. These findings are particularly
      concerning given the significant barriers that ethnic minorities and safety-net
      populations already face in timely access to medical care.

PMID- 29052176
TI  - Factors Associated with American Indian Mental Health Service Use in Comparison
      with White Older Adults.
AB  - OBJECTIVE: Our objective was to identify the factors that impact mental health
      service use among American Indian (AI) older adults living in South Dakota
      compared to their White counterparts. DESIGN AND METHODS: Using a cross-sectional
      design with 735 participants (n = 502 Whites, n = 233 AIs), we used ordinal
      regressions to analyze the extent to which predisposing, need, and
      enabling/hindering factors predicted the level of mental health service
      utilization. RESULTS: White older adults used more mental health services as
      compared with AI older adults. For both groups, more adverse childhood
      experiences along with prior negative experience with mental health service use
      were significantly related to an increased level of mental health service use.
      Compared to their White counterparts, AI older adults who reported a higher level
      of depressive symptoms, better self-perceived physical health, and a more
      positive attitude toward mental health services tended to use more mental health
      services. CONCLUSIONS: To reduce mental health disparities among AI older adults,
      community, local government, and academic partners should pay attention to how to
      encourage the use of mental health services to meet the unique needs of AI older
      adults.

PMID- 29052177
TI  - Prognostic Value of Osteoprotegerin and sRANKL in Bronchoalveolar Lavage Fluid of
      Patients with Advanced Non-small Cell Lung Cancer.
AB  - Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of
      nuclear factor-kappa B ligand (sRANKL). OPG promotes endothelial cell survival
      and neoangiogenesis. Dysregulation of the OPG/RANKL system has been detected in
      several tumors. In the present study, we evaluated the clinical usefulness of OPG
      and sRANKL assessment in bronchoalveolar lavage fluid (BALF) of patients with
      advanced non-small cell lung cancer (NSCLC). We measured the concentration of OPG
      and sRANKL in BALF of 44 NSCLC patients and 15 healthy volunteers taken as
      control subjects. The OPG content was higher in the NSCLC group than that in
      controls [0.48 (0.12-1.45) vs. 0.23 (0.14-0.75) pmol/l; p = 0.0001]. There were
      no significant differences in sRANKL content between the NSCLC and control groups
      [1.22 (0.74-23.00) vs. 1.12 (0.79-4.39) pmol/l; p = 0.67]. However, we found that
      the greater the level of sRANKL in NSCLC patients, the shorter the overall
      survival. We found a correlation between the content of sRANKL and the percentage
      of lymphocytes in BALF of NSCLC patients (r = 0.52; p = 0.041). We conclude that
      NSCLC patients have a higher content of OPG in BALF than healthy people. A high
      level of sRANKL in BALF of NSCLC patients may predict worse survival.

PMID- 29052178
TI  - HMGA1 is a novel transcriptional regulator of the FoxO1 gene.
AB  - PURPOSE: The forkhead transcription factor (FoxO1) is a master transcriptional
      regulator of fundamental cellular processes ranging from cell proliferation and
      differentiation to inflammation and metabolism. However, despite its relevance,
      the mechanism(s) underlying FoxO1 gene regulation are largely unknown. We have
      previously shown that the chromatin factor high-mobility group A1 (HMGA1) plays a
      key role in the transcriptional regulation of glucose-responsive genes, including
      some that are involved in FoxO1-mediated glucose metabolism. Here we investigated
      the impact of HMGA1 on FoxO1 gene expression. METHODS: FoxO1 protein and gene
      expression studies were performed by Western blot analysis combined with qRT-PCR
      of material from human cultured cells and EBV-transformed lymphoblasts, and from
      primary cultured hepatocytes from wild-type and Hmga1 -/- mice. Reporter gene
      assays and chromatin immunoprecipitation for binding of HMGA1 to the endogenous
      FoxoO1 locus were performed in cells overexpressing HMGA1 and in cells pretreated
      with siRNA targeting HMGA1. RESULTS: HMGA1 increased FoxO1 mRNA and protein
      expression in vitro, in cultured HepG2 and HEK-293 cells by binding FoxO1 gene
      promoter, thereby activating FoxO1 gene transcription. Forced expression of HMGA1
      in primary cultured hepatocytes from Hmga1 -/- mice and in EBV-transformed
      lymphoblasts from subjects with reduced expression of endogenous HMGA1 increased
      FoxO1 mRNA and protein levels. CONCLUSION: These findings may contribute to the
      understanding of FoxO1 gene regulation and its role in metabolism.

PMID- 29052179
TI  - Thyroid reoperation using intraoperative neuromonitoring.
AB  - PURPOSE: Thyroid reoperations are at a high risk of recurrent laryngeal nerve
      (RLN) injury. The aim of the study was to investigate whether the use of
      intraoperative neuromonitoring (IONM) can aid in the RLN identification and
      minimize the risk of its injury, in comparison with visual RLN identification.
      METHODS: This was a retrospective cohort study of patients who underwent thyroid
      reoperations with and without the use of IONM. Primary endpoint was the RLN
      identification rate; secondary: the prevalence of RLN injury, the frequency of
      total thyroidectomies, and the course of the RLN. RESULTS: The study involved 61
      patients undergoing thyroid reoperation among whom 24 were operated on with
      visual RLN identification only, while 37 procedures used IONM. In the non
      monitored reoperations, 44.4% of the RLN were visually identified, as opposed to
      91.6% in the IONM group (p < 0.001). Transient paresis occurred in three nerves
      with visualization (6.6%), and in one in IONM group 1.6% (p = 0.185). Permanent
      paresis occurred in the group with visualization (6.6%), as opposed to none with
      neuromonitoring. The extent of resection in both groups was significantly
      different (p = 0.043). Total, near-total thyroidectomies, Dunhill operations and
      subtotal thyroidectomies were performed in 71, 17, 4, and 8% in the visualization
      group, and in 94, 0, 3, and 3%, respectively, in the IONM group. A non-anatomical
      RLN course was observed in 80% of the reoperations with IONM. CONCLUSIONS:
      Thyroid reoperation should be performed using IONM, because it allows for a
      significantly improved RLN identification rate and a significantly more radical
      resection.

PMID- 29052180
TI  - Effectiveness of myoinositol for polycystic ovary syndrome: a systematic review
      and meta-analysis.
AB  - PURPOSE: To assess the effectiveness and safety of myoinositol for patients with
      PCOS. METHODS: In this meta-analysis, data from randomized controlled trials are
      obtained to assess the effects of myoinositol vs. placebo or western medicine in
      women with PCOS. The study's registration number is CRD42017064563. The primary
      outcomes included total testosterone, estradiol (E2) and the homeostatic model
      assessment (HOMA) of insulin resistance. RESULT: Ten trials involving 573
      patients were included. The meta-analysis results show that: compared with the
      control group, myoinositol may improve HOMA index (WMD -0.65; 95% CI -1.02, 
      0.28; P = 0. 0005) and increase the E2 level (WMD 16.16; 95% CI 2.01, 30.31; P =
      0. 03); while there is no enough strong evidence that the myoinositol has an
      effect on the total testosterone level (WMD -16.11; 95% CI -46.08, 13.86; P = 0.
      29). CONCLUSION: Based on current evidence, myoinositol may be recommended for
      the treatment of PCOS with insulin resistance, as well as for improving symptoms
      caused by decreased estrogen in PCOS.

PMID- 29052182
TI  - Profiling Developmentally and Environmentally Controlled Chromatin Reprogramming.
AB  - Dynamic reshuffling of the chromatin landscape is a recurrent theme orchestrated
      in many, if not all, plant developmental transitions and adaptive responses.
      Spatiotemporal variations of the chromatin properties on regulatory genes and on
      structural genomic elements trigger the establishment of distinct transcriptional
      contexts, which in some instances can epigenetically be inherited. Studies on
      plant cell plasticity during the differentiation of stem cells, including
      gametogenesis, or the specialization of vegetative cells in various organs, as
      well as the investigation of allele-specific gene regulation have long been
      impaired by technical challenges in generating specific chromatin profiles in
      complex or hardly accessible cell populations. Recent advances in increasing the
      sensitivity of genome-enabled technologies and in the isolation of specific cell
      types have allowed for overcoming such limitations. These developments hint at
      multilevel regulatory events ranging from nucleosome accessibility and
      composition to higher order chromatin organization and genome topology.
      Uncovering the large extent to which chromatin dynamics and epigenetic processes
      influence gene expression is therefore not surprisingly revolutionizing current
      views on plant molecular genetics and (epi)genomics as well as their perspectives
      in eco-evolutionary biology. Here, we introduce current methodologies to probe
      genome-wide chromatin variations for which protocols are detailed in this book
      chapter, with an emphasis on the plant model species Arabidopsis.

PMID- 29052183
TI  - Profiling DNA Methylation Using Bisulfite Sequencing (BS-Seq).
AB  - DNA cytosine methylation is one of the most abundant epigenetic marks found in
      the plant nuclear genome. Bisulfite sequencing (BS-Seq) is the method of choice
      for profiling DNA cytosine methylation genome-wide at a single nucleotide
      resolution. The basis of this technique is that the unmethylated cytosine can be
      deaminated to uracil by sodium bisulfite, while the methylated cytosine is
      resistant to the treatment. By deep sequencing of the bisulfite converted genomic
      DNA, the methylation level of each mappable cytosine position in the genome could
      be measured. In this chapter, we present a detailed 2-day protocol for performing
      a BS-Seq experiment and a simple bioinformatic workflow for wet lab biologists to
      visualize the methylation data.

PMID- 29052184
TI  - Bisulfite Sequencing Using Small DNA Amounts.
AB  - Bisulfite sequencing (BS-seq) enables the detection of DNA methylation at
      cytosine residues (5mC) at single-nucleotide resolution. For many applications, a
      limiting factor of conventional BS-seq protocols is the high amount of DNA
      required, since the treatment with bisulfite causes severe DNA fragmentation.
      Here, we describe a post-bisulfite tagging method that accounts for this problem.
      Illumina-compatible BS-seq libraries can be obtained from as little as five
      single haploid maize cells, enabling whole genome BS-seq (WGBS) for the
      generation of genome-wide, cell-type specific DNA methylation profiles. The
      method can also be used to analyze defined fractions of genomes from limited
      samples by Reduced Representation Bisulfite Sequencing (RRBS). This involves
      restriction digestion, gel separation and fragment elution prior to BS-seq
      library preparation to enrich certain areas of the genome. This reduction of
      represented genomic regions lowers the sequencing cost considerably while
      providing an accurate assessment of total genome-wide DNA methylation levels and
      assessment of DNA methylation in categorical genomic regions.

PMID- 29052185
TI  - Identification of Differentially Methylated Regions in the Genome of Arabidopsis
      thaliana.
AB  - DNA methylation profiling in the epigenome of Arabidopsis thaliana (Arabidopsis)
      has provided great insights in the role of this epigenetic mark for the
      regulation of transcription in plants, and is often based on high-throughput
      sequencing. The analysis of these data involves a series of steps including
      quality checks, filtering, alignment, identification of methyl-cytosines, and the
      identification of differentially methylated regions. This chapter outlines the
      computational methodology required to profile genome-wide differential
      methylation patterns based on publicly available Arabidopsis base-resolution
      bisulfite sequencing data. The methylPipe Bioconductor package is adopted for the
      identification of the differentially methylated regions, and all the steps from
      the raw data to the required input are described in detail.

PMID- 29052186
TI  - A Rapid and Efficient ChIP Protocol to Profile Chromatin Binding Proteins and
      Epigenetic Modifications in Arabidopsis.
AB  - Chromatin immunoprecipitation (ChIP) is a widely used and very powerful procedure
      to identify the proteins that are associated with the DNA to regulate
      developmental processes. These proteins can be transcription factors, or specific
      histone variants and modified histones, which are all crucial for gene
      regulation. In order to obtain reliable results, ChIP must be carried out under
      highly reproducible conditions. Here, we describe a simple and fast ChIP protocol
      adapted for Arabidopsis seedlings, which can serve as a basis for other species,
      organs or more sophisticated procedures, such as the sequential ChIP. We also
      provide user-oriented troubleshooting to increase the chances of successful
      applications.

PMID- 29052187
TI  - Sequential ChIP Protocol for Profiling Bivalent Epigenetic Modifications
      (ReChIP).
AB  - Identification of chromatin modifications, e.g., histone acetylation and
      methylation, among others, is widely carried out by using a chromatin
      immunoprecipitation (ChIP) strategy. The information obtained with these
      procedures is useful to gain an overall picture of modifications present in all
      cells of the population under study. It also serves as a basis to figure out the
      mechanisms of chromatin organization and gene regulation at the population level.
      However, the ultimate goal is to understand gene regulation at the level of
      single chromatin fibers. This requires the identification of chromatin
      modifications that occur at a given genomic location and within the same
      chromatin fiber. This is achieved by following a sequential ChIP strategy using
      two antibodies to distinguish different chromatin modifications. Here, we
      describe a sequential ChIP protocol (Re-ChIP), paying special attention to the
      controls needed and the required steps to obtain meaningful and reproducible
      results. The protocol is developed for young Arabidopsis seedlings but could be
      adapted to other plant materials.

PMID- 29052181
TI  - Probiotic strains and mechanistic insights for the treatment of type 2 diabetes.
AB  - INTRODUCTION: The intestinal microbial composition appears to differ between
      healthy controls and individuals with Type 2 diabetes (T2D). This observation has
      led to the hypothesis that perturbations of the intestinal microbiota may
      contribute to the development of T2D. Manipulations of the intestinal microbiota
      may therefore provide a novel approach in the prevention and treatment of T2D.
      Indeed, fecal transplants have shown promising results in both animal models for
      obesity and T2D and in human clinical trials. To avoid possible complications
      associated with fecal transplants, probiotics are considered as a viable
      alternative therapy. An important, however often underappreciated, characteristic
      of probiotics is that individual strains may have different, even opposing,
      effects on the host. This strain specificity exists also within the same species.
      A comprehensive understanding of the underlying mechanisms at the strain level is
      therefore crucial for the selection of suitable probiotic strains. PURPOSE: The
      aim of this review is to discuss the mechanisms employed by specific probiotic
      strains of the Lactobacillus and the Bifidobacterium genuses, which showed
      efficacy in the treatment of obesity and T2D. Some probiotic strains employ
      recurring beneficial effects, including the production of anti-microbial lactic
      acid, while other strains display highly unique features, such as hydrolysis of
      tannins. CONCLUSION: A major obstacle in the evaluation of probiotic strains lays
      in the great number of strains, differences in detection methodology and measured
      outcome parameters. The understanding of further research should be directed
      towards the development of standardized evaluation methods to facilitate the
      comparison of different studies.

PMID- 29052188
TI  - A Method to Identify Nucleolus-Associated Chromatin Domains (NADs).
AB  - The nuclear context needs to be taken into consideration to better understand the
      mechanisms shaping the epigenome and its organization, and therefore its impact
      on gene expression. For example, in Arabidopsis, heterochromatin is
      preferentially localized at the nuclear and the nucleolar periphery. Although
      chromatin domains associating with the nuclear periphery remain to be identified
      in plant cells, Nucleolus Associated chromatin Domains (NADs) can be identified
      thanks to a protocol allowing the isolation of pure nucleoli. We describe here
      the protocol enabling the identification of NADs in Arabidopsis. Providing the
      transfer of a nucleolus marker as described here in other crop species, this
      protocol is broadly applicable.

PMID- 29052189
TI  - Cell Type-Specific Profiling of Chromatin Modifications and Associated Proteins.
AB  - Progression of a cell along a differentiation path is characterized by changes in
      gene expression profiles. Alterations of these transcriptional programs result
      from cell type-specific transcription factors that act in a dynamic chromatin
      environment. Understanding the precise contribution of these molecular factors
      during the differentiation process requires accessing specific cell types within
      a developing organ. This chapter describes a streamlined and alternative version
      of INTACT, a method enabling the isolation of specific cell populations by
      affinity-purification of tagged nuclei and the subsequent analysis of gene
      expression, transcription factor binding profiles, as well as chromatin state at
      a genome-wide scale. In particular, modifications of the nuclei isolation,
      capture, and purification procedures are proposed that improve time scale, yield,
      and purity. In addition, the combination of different tags enables the analysis
      of distinct cell populations from a single transgenic line and the subtractive
      purification of subpopulations of cells, including those for which no specific
      promoter is available. Finally, we describe a chromatin immunoprecipitation
      protocol that has been successfully used to profile histone modifications and
      other chromatin-associated proteins such as RNA Polymerase II in different cell
      populations of the Arabidopsis root, including the quiescent center of the stem
      cell niche.

PMID- 29052190
TI  - Mapping of Histone Modifications in Plants by Tandem Mass Spectrometry.
AB  - To get an insight into the mechanisms of gene expression regulation in eukaryotic
      organisms, it is necessary to decipher the connection between the different
      chemical modifications occurring on the chromatin, at both the DNA and the
      associated histone proteins. Histones are basic proteins, which pack the DNA into
      nucleosomes, and are hot spots for several posttranslational modifications.
      Elucidating combinatorial histone modifications co-occurring on the same histone
      protein will greatly contribute to our understanding of the mechanisms involved
      in the development of eukaryotes. The advancements in mass spectrometry
      technologies, including sensitivity, accuracy, and ionization strategies, have
      significantly contributed to the identification of novel single and combinatorial
      modifications on histones isolated from model organisms. In this chapter, we
      describe detailed protocols applied for the extraction, purification, and
      processing of histones for subsequent analysis by tandem mass spectrometry, using
      Brassica oleracea (cauliflower), a close relative of Arabidopsis thaliana.

PMID- 29052191
TI  - Histone H1 Purification and Post-Translational Modification Profiling by High
      Resolution Mass Spectrometry.
AB  - It has proven particularly difficult to purify Linker (H1) histones from the
      model plant Arabidopsis thaliana. This is most likely due to its low nuclear DNA
      content and the abundance of substances that interfere with protein isolation.
      These problems have hindered the use of Arabidopsis for in-depth characterization
      of nuclear proteins by modern techniques based on mass spectrometry (MS). Here,
      we describe an improved methodology for preparing pure Arabidopsis H1s and
      separating them by HPLC into fractions corresponding to nonallelic variants. In
      addition, we outline basic approaches enabling the identification of
      posttranslational modifications of H1 by MS and their mapping by digestion with
      different proteases. We also discuss the analysis and interpretation of the
      acquired data.

PMID- 29052192
TI  - Profiling Nucleosome Occupancy by MNase-seq: Experimental Protocol and
      Computational Analysis.
AB  - Nucleosomes are the basic repeating units of eukaryotic chromatin. They play
      important roles in chromatin compaction and gene regulation. Therefore, it is
      important to profile the in vivo locations of nucleosomes in the genome. Here we
      illustrate how to profile nucleosome occupancy at genome-wide scale using
      micrococcal nuclease (MNase) digestion combined with high throughput Illumina
      sequencing (MNase-seq). Nucleosome-associated DNA is relatively insensitive to
      digestion by micrococcal nuclease (MNase). Upon mild MNase treatment, the
      undigested nucleosomal DNA can be purified and sequenced allowing a precise
      localization of in vivo nucleosomes at a genome-wide level.

PMID- 29052193
TI  - Identification of Open Chromatin Regions in Plant Genomes Using ATAC-Seq.
AB  - Identifying and characterizing highly accessible chromatin regions assists in
      determining the location of genomic regulatory elements and understanding
      transcriptional regulation. In this chapter, we describe an approach to map
      accessible chromatin features in plants using the Assay for Transposase
      Accessible Chromatin, combined with high-throughput sequencing (ATAC-seq), which
      was originally developed for cultured animal cells. This technique utilizes a
      hyperactive Tn5 transposase to cause DNA cleavage and simultaneous insertion of
      sequencing adapters into open chromatin regions of the input nuclei. The
      application of ATAC-seq to plant tissue has been challenging due to the
      difficulty of isolating nuclei sufficiently free of interfering organellar DNA.
      Here we present two different approaches to purify plant nuclei for ATAC-seq: the
      INTACT method (Isolation of Nuclei TAgged in specific Cell Types) to isolate
      nuclei from individual cell types of the plant, and tissue lysis followed by
      sucrose sedimentation to isolate sufficiently pure total nuclei. We provide
      detailed instructions for transposase treatment of nuclei isolated using either
      approach, as well as subsequent preparation of ATAC-seq libraries. Sequencing
      ready ATAC-seq libraries can be prepared from plant tissue in as little as one
      day. The procedures described here are optimized for Arabidopsis thaliana but can
      also be applied to other plant species.

PMID- 29052194
TI  - Unraveling the Complex Epigenetic Mechanisms that Regulate Gene Activity.
AB  - Our understanding of the epigenetic mechanisms that regulate gene expression has
      been largely increased in recent years by the development and refinement of
      different techniques. This has revealed that gene transcription is highly
      influenced by epigenetic mechanisms, i.e., those that do not involve changes in
      the genome sequence, but rather in nuclear architecture, chromosome conformation
      and histone and DNA modifications. Our understanding of how these different
      levels of epigenetic regulation interact with each other and with classical
      transcription-factor based gene regulation to influence gene transcription has
      just started to emerge. This review discusses the latest advances in unraveling
      the complex interactions between different types of epigenetic regulation and
      transcription factor activity, with special attention to the approaches that can
      be used to study these interactions.

PMID- 29052195
TI  - Technical Review: A Hitchhiker's Guide to Chromosome Conformation Capture.
AB  - The introduction of chromosome conformation capture (3C) technologies boosted the
      field of 3D-genome research and significantly enhanced the available toolset to
      study chromosomal architecture. 3C technologies not only offer increased
      resolution compared to the previously dominant cytological approaches but also
      allow the simultaneous study of genome-wide 3D chromatin contacts, thereby
      enabling a candidate-free perspective on 3D-genome architecture. Since its
      introduction in 2002, 3C technologies evolved rapidly and now constitute a
      collection of tools, each with their strengths and pitfalls with respect to
      specific research questions. This chapter aims at guiding 3C novices through the
      labyrinth of potential applications of the various family members, hopefully
      providing a valuable basis for choosing the appropriate strategy for different
      research questions.

PMID- 29052196
TI  - 3C in Maize and Arabidopsis.
AB  - With Chromosome Conformation Capture (3C), the relative interaction frequency of
      one chromosomal fragment with another can be determined. The technique is
      especially suited for unraveling the 3D organization of specific loci when
      focusing on aspects such as enhancer-promoter interactions or other topological
      conformations of the genome. 3C has been extensively used in animal systems,
      among others providing insight into gene regulation by distant cis-regulatory
      elements. In recent years, the 3C technique has been applied in plant research.
      However, the complexity of plant tissues prevents direct application of existing
      protocols from animals. Here, we describe an adapted protocol suitable for plant
      tissues, especially Arabidopsis thaliana and Zea mays.

PMID- 29052197
TI  - Profiling Histone Modifications in Synchronized Floral Tissues for Quantitative
      Resolution of Chromatin and Transcriptome Dynamics.
AB  - Covalent histone modifications and their effects on chromatin state and
      accessibility play a key role in the regulation of gene expression in eukaryotes.
      To gain insights into their functions during plant growth and development, the
      distribution of histone modifications can be analyzed at a genome-wide scale
      through chromatin immunoprecipitation assays followed by sequencing of the
      isolated genomic DNA. Here, we present a protocol for systematic analysis of the
      distribution and dynamic changes of selected histone modifications, during flower
      development in the model plant Arabidopsis thaliana. This protocol utilizes a
      previously established floral induction system to synchronize flower development,
      which allows the collection of sufficient plant material for analysis by genomic
      technologies. In this chapter, we describe how to use this system to study, from
      the same set of samples, chromatin and transcriptome dynamics during early stages
      of flower formation.

PMID- 29052199
TI  - Identification of In Planta Protein-Protein Interactions Using IP-MS.
AB  - Gene regulation by transcription factors involves complex protein interaction
      networks, which include chromatin remodeling and modifying proteins as an
      integral part. Decoding these protein interactions is crucial for our
      understanding of chromatin-mediated gene regulation. Here, we describe a method
      for the immunoprecipitation of in planta nuclear protein complexes followed by
      mass spectrometry (IP-MS) to identify interactions between transcription factors
      and chromatin remodelers/modifiers in plants. In addition to a step-by-step bench
      protocol for immunoprecipitation and subsequent mass spectrometry, we provide
      guidelines and pointers on necessary controls and data analysis approaches.

PMID- 29052198
TI  - De Novo Identification of sRNA Loci and Non-coding RNAs by High-Throughput
      Sequencing.
AB  - Non-coding RNA transcripts, such as long non-coding RNAs, miRNAs, siRNAs, and
      transposon-originating transcripts, are involved in the regulation of RNA
      stability, protein translation, and/or the modulation of chromatin states. RNA
      Seq can be used to catalog this diversity of novel transcripts and a joint
      analysis of these transcriptomic data can provide useful insights into epigenetic
      regulation of dynamic responses such as the stress response, which may not be
      deciphered from individual analysis of single transcript categories. Here, we
      present a protocol that allows the identification and analysis of small RNAs and
      long non-coding RNAs, together with the comparison of these species between
      different sample types.

PMID- 29052200
TI  - RNA Immunoprecipitation Protocol to Identify Protein-RNA Interactions in
      Arabidopsis thaliana.
AB  - The role of RNA-binding proteins in the regulation of epigenetic processes has
      received increasing attention in the past decades. In particular noncoding RNAs
      have been shown to play a role in chromatin loop formation, recruitment of
      chromatin modifiers and RNA-dependent DNA methylation. In plants, the
      identification of specific RNA-protein interactions is now rising, facilitated by
      the development of specific approaches for plant tissues. Here, we present a
      simple one-day RNA immunoprecipitation (RIP) protocol adapted for Arabidopsis,
      suited for the identification of RNAs that are associated with a protein-of
      interest in planta.

PMID- 29052201
TI  - In Vitro Assays to Measure Histone Methyltransferase Activity Using Different
      Chromatin Substrates.
AB  - In vitro histone modification (HM) assays are used to characterize the activity
      of chromatin-modifying enzymes. These assays provide information regarding the
      modification sites on histones, the product specificity, and the impact of other
      histone or nucleotide modifications on enzyme activity. In particular, histone
      methyltransferase (HMT) assays have been instrumental in elucidating the activity
      and site specificity of many plant HMT enzymes. In this chapter, we describe a
      general protocol that can be used to perform HMT assays using different chromatin
      substrates, detection methods, and enzymes directly purified from plant material
      or heterologous sources.

PMID- 29052202
TI  - Identification of Parent-of-Origin-Dependent QTLs Using Bulk-Segregant Sequencing
      (Bulk-Seq).
AB  - Parent-of-origin effects play important roles in plant reproduction and are often
      mediated by epigenetic modifications at the histone or DNA level. However, the
      genetic basis underlying these modifications can be challenging to identify.
      Here, we describe an approach (Bulk-Seq) that can be used to map loci mediating
      parent-of-origin-dependent effects using whole-genome sequencing of pools of DNA.

PMID- 29052203
TI  - QTLepi Mapping in Arabidopsis thaliana.
AB  - While DNA sequence variation is known to be a major driver of phenotypic
      divergence, epigenetic variation has long been disregarded. One reason for that
      was the lack of suitable tools. The creation of epigenetically divergent but
      otherwise largely isogenic Arabidopsis populations has now alleviated some of
      these constraints. Epigenetic recombinant inbred line (epiRIL) populations allow
      for examining the effects of epigenetic variation on phenotypes. In addition,
      epiRILs enabled the development of epigenetic quantitative trait locus (QTLepi)
      mapping, an approach to identify causal epigenetic factors. Here, we describe the
      successive steps of QTLepi mapping in a broad sense, from the creation of
      epigenetically divergent populations to the identification of causal genes
      underlying particular phenotypes in Arabidopsis.

PMID- 29052204
TI  - A Compendium of Methods to Analyze the Spatial Organization of Plant Chromatin.
AB  - The long linear chromosomes of eukaryotic organisms are tightly packed into the
      nucleus of the cell. Beyond a first organization into nucleosomes and higher
      order chromatin fibers, the positioning of nuclear DNA within the three
      dimensional space of the nucleus plays a critical role in genome function and
      gene expression. Different techniques have been developed to assess nanoscale
      chromatin organization, nuclear position of genomic regions or specific chromatin
      features and binding proteins as well as higher-order chromatin organization.
      Here, I present an overview of imaging and molecular techniques applied to study
      nuclear architecture in plants, with special attention to the related protocols
      published in the "Plant Chromatin Dynamics" edition from Methods in Molecular
      Biology.

PMID- 29052206
TI  - Cell-Type Specific Chromatin Analysis in Whole-Mount Plant Tissues by
      Immunostaining.
AB  - Chromatin organization in eukaryotes is highly dynamic, playing fundamental roles
      in regulating diverse nuclear processes including DNA replication, transcription,
      and repair. Thus, the analysis of chromatin organization is of great importance
      for the elucidation of chromatin-mediated biological processes. Immunostaining
      coupled with imaging is one of the most powerful tools for chromatin analysis at
      the cellular level. However, in plants, it is sometimes technically challenging
      to apply this method due to the inaccessibility of certain cell types and/or poor
      penetration of the reagents into plant tissues and cells. To circumvent these
      limitations, we developed a highly efficient protocol enabling the analysis of
      chromatin modifications and nuclear organization at the single-cell level with
      high resolution in whole-mount plant tissues. The main procedure consists of five
      steps: (1) tissue fixation; (2) dissection and embedding; (3) tissue processing;
      (4) antibody incubation; and (5) imaging. This protocol has been simplified for
      the processing of multiple samples without the need for laborious tissue
      sectioning. Additionally, it preserves cellular morphology and chromatin
      organization, allowing comparative analyses of chromatin organization between
      different cell types or developmental stages. This protocol was successfully used
      for various tissues of different plant species, including Arabidopsis thaliana,
      Oryza sativa (rice), and Zea mays (maize). Importantly, this method is very
      useful to analyze poorly accessible tissues, such as female meiocytes,
      gametophytes, and embryos.

PMID- 29052205
TI  - Localization of Chromatin Marks in Arabidopsis Early Embryos.
AB  - During early embryo development, profound changes in chromatin structure and
      regulation take place. It is difficult to study these changes in plant embryos
      however, largely because of their relative inaccessibility, which impedes the
      application of current epigenomic and biochemistry protocols. To circumvent this
      issue and to analyze the epigenetic status of the embryo at both the cellular and
      subcellular level, we describe here a simple method to immunolocalize chromatin
      marks in whole mount early Arabidopsis embryos, either within maternal tissues or
      isolated from seeds. We show that this protocol can be combined with fluorescent
      protein markers, allowing for the simultaneous detection of several chromatin
      components and/or cell fate markers. This new protocol will facilitate
      deciphering the epigenetic circuits controlling early embryogenesis in plants.

PMID- 29052207
TI  - Measuring Dynamics of Histone Proteins by Photobleaching in Arabidopsis Roots.
AB  - Histone proteins play an important role in determining chromatin structure and
      gene expression. Studies in several systems have established that histones are in
      continuous turnover within the chromatin. It is therefore important to
      quantitatively measure the binding dynamics of these proteins in vivo.
      Photobleaching-based approaches such as fluorescence recovery after
      photobleaching (FRAP) are advantageous in that they are applied to living cells
      at a single cell level. In this chapter, I provide a detailed experimental
      protocol on how to perform histone FRAP experiments in Arabidopsis thaliana roots
      and how to analyze the most important parameters.

PMID- 29052208
TI  - Fluorescence In Situ Hybridization (FISH) and Immunolabeling on 3D Preserved
      Nuclei.
AB  - The spatial distribution of genes in the nucleus emerges as an important factor
      in gene regulation and epigenetics. The position of loci relative to each other,
      to nuclear landmarks such as the nucleolus and chromocenters, as well as to
      chromatin proteins is therefore highly interesting. With fluorescent in situ
      hybridization (FISH) specific DNA sequences can be stained and antibodies allow
      the detection of specific proteins. Here, we present two protocols that preserve
      the 3D structure of nuclei. With whole-mount FISH, specific sequences can be
      stained in intact tissues and, secondly, a combined immunolabeling and FISH
      protocol on acrylamide-embedded nuclei makes it possible to stain DNA sequences
      and proteins simultaneously.

PMID- 29052210
TI  - A Method for Testing Random Spatial Models on Nuclear Object Distributions.
AB  - The cell nucleus is a structurally complex and dynamic organelle ensuring key
      biological functions. Complex relationships between nuclear structure and
      functions require a better understanding of the three-dimensional organization of
      the genome and of the subnuclear compartments. Quantitative image analysis
      coupled with spatial statistics and modeling is a relevant approach to address
      these questions. In this chapter, we describe a step-by-step procedure to process
      images and to test a spatial random model for the distribution of nuclear objects
      using chromocenters as an example. More elaborate models can be designed on the
      basis of the random model by introducing additional and more complex constraints
      to better fit observations and to question determinants of these spatial
      organizations.

PMID- 29052209
TI  - High-Affinity LNA-DNA Mixmer Probes for Detection of Chromosome-Specific
      Polymorphisms of 5S rDNA Repeats in Arabidopsis thaliana.
AB  - Fluorescence in situ hybridization is a standard technique to visualize specific
      DNA sequences by hybridization with fluorescent probes and, most commonly, relies
      on DNA probes generated by nick translation. In this chapter, we describe the use
      of directly labeled LNA-DNA mixmer probes for the rapid detection of repetitive
      sequences on Arabidopsis thaliana nuclei spreads. We further demonstrate that due
      to the high thermal stability of the heteroduplexes and the resulting elevated
      binding affinity of LNA-DNA mixmer probes for their target DNA, these probes can
      be used to discriminate between repetitive sequences differing by only a few
      single nucleotide polymorphisms.

PMID- 29052211
TI  - Technical Review: Cytogenetic Tools for Studying Mitotic Chromosomes.
AB  - Significant advances in chromosome preparation and other techniques have greatly
      increased the potential of plant cytogenetics in recent years. Increase in
      longitudinal resolution using DNA extended fibers as well as new developments in
      imaging and signal amplification technologies have enhanced the ability of FISH
      to detect small gene targets. The combination of fluorescence in situ
      hybridization with immunocytochemistry allows the investigation of cell events,
      chromosomal rearrangements and chromatin features typical for plant nuclei.
      Chromosome manipulation techniques using microdissection and flow sorting have
      accelerated the analysis of complex plant genomes. Together, the different
      cytogenetic approaches are invaluable for the unravelling of detailed structures
      of plant chromosomes, which are of utmost importance for the study of genome
      properties, DNA replication and gene regulation. In this technical review,
      different cytogenetic approaches are discussed for the analysis of plant
      chromosomes, with a focus on mitotic chromosomes.

PMID- 29052212
TI  - Technical Review: Microscopy and Image Processing Tools to Analyze Plant
      Chromatin: Practical Considerations.
AB  - In situ nucleus and chromatin analyses rely on microscopy imaging that benefits
      from versatile, efficient fluorescent probes and proteins for static or live
      imaging. Yet the broad choice in imaging instruments offered to the user poses
      orientation problems. Which imaging instrument should be used for which purpose?
      What are the main caveats and what are the considerations to best exploit each
      instrument's ability to obtain informative and high-quality images? How to infer
      quantitative information on chromatin or nuclear organization from microscopy
      images? In this review, we present an overview of common, fluorescence-based
      microscopy systems and discuss recently developed super-resolution microscopy
      systems, which are able to bridge the resolution gap between common fluorescence
      microscopy and electron microscopy. We briefly present their basic principles and
      discuss their possible applications in the field, while providing experience
      based recommendations to guide the user toward best-possible imaging. In addition
      to raw data acquisition methods, we discuss commercial and noncommercial
      processing tools required for optimal image presentation and signal evaluation in
      two and three dimensions.

PMID- 29052213
TI  - Automated 3D Gene Position Analysis Using a Customized Imaris Plugin:
      XTFISHInsideNucleus.
AB  - Fluorescence in situ hybridization (FISH) is commonly used to visualize
      chromosomal regions or genomic loci within the nucleus, and can largely
      contribute to unraveling the link between structure and function in the nucleus.
      Three-dimensional (3D) analyses are required to best capture the nucleus'
      organizing principles, but the experimental setup and computational analyses are
      far from trivial. Here, we present a robust workflow for 3D FISH against repeats
      and single copy loci in embedded intact nuclei from Arabidopsis leaves. We then
      describe in detail the image acquisition, subsequent image deconvolution before
      3D image processing, and the image reconstruction. We developed an automated
      batch image processing pipeline using a customized, open source plugin
      implemented in the Imaris environment.

PMID- 29052214
TI  - Quantitative 3D Analysis of Nuclear Morphology and Heterochromatin Organization
      from Whole-Mount Plant Tissue Using NucleusJ.
AB  - Image analysis is a classical way to study nuclear organization. While nuclear
      organization used to be investigated by colorimetric or fluorescent labeling of
      DNA or specific nuclear compartments, new methods in microscopy imaging now
      enable qualitative and quantitative analyses of chromatin pattern, and nuclear
      size and shape. Several procedures have been developed to prepare samples in
      order to collect 3D images for the analysis of spatial chromatin organization,
      but only few preserve the positional information of the cell within its tissue
      context. Here, we describe a whole mount tissue preparation procedure coupled to
      DNA staining using the PicoGreen(r) intercalating agent suitable for image
      analysis of the nucleus in living and fixed tissues. 3D Image analysis is then
      performed using NucleusJ, an open source ImageJ plugin, which allows for
      quantifying variations in nuclear morphology such as nuclear volume, sphericity,
      elongation, and flatness as well as in heterochromatin content and position in
      respect to the nuclear periphery.

PMID- 29052215
TI  - Transmission Electron Microscopy Imaging to Analyze Chromatin Density
      Distribution at the Nanoscale Level.
AB  - Transmission electron microscopy (TEM) is used to study the fine ultrastructural
      organization of cells. Delicate specimen preparation is required for results to
      reflect the "native" ultrastructural organization of subcellular features such as
      the nucleus. Despite the advent of high-resolution, fluorescent imaging of
      chromatin components, TEM still provides a unique and complementary level of
      resolution capturing chromatin organization at the nanoscale level. Here, we
      describe the workflow, from tissue preparation, TEM image acquisition and image
      processing, for obtaining a quantitative description of chromatin density
      distribution in plant cells, informing on local fluctuations and periodicity.
      Comparative analyses then allow to elucidate the structural changes induced by
      developmental or environmental cues, or by mutations affecting specific chromatin
      modifiers at the nanoscale level. We argue that this approach remains affordable
      and merits a renewed interest by the plant chromatin community.

PMID- 29052216
TI  - Polycystic ovarian syndrome: Prevalence and impact on the wellbeing of Australian
      women aged 16-29 years.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common condition among
      reproductive-aged women. However, its exact prevalence is unknown. AIMS: To
      determine the prevalence of PCOS in Australian women aged 16-29 years using the
      National Institutes of Health (NIH) criteria compared to self-reported PCOS, to
      compare co-morbidities between the groups and to determine the most distressing
      aspect of a diagnosis of PCOS for these young women. MATERIALS AND METHODS:
      Participants were recruited from the Young Female Health Initiative (YFHI) and
      Safe-D studies. Participants completed questionnaires, physical examinations and
      blood tests from 2012 to 2016. In March 2016, two supplementary questionnaires
      were distributed: the first, comprising questions on reproductive health and
      impact of diagnosis, was sent to participants who self-reported having PCOS in
      the original studies. The second, comprising general reproductive health
      questions, was sent to the remainder. RESULTS: The prevalence of PCOS, according
      to the NIH criteria, was 12% (31/254), while the prevalence of self-reported PCOS
      was 8% (23/300). Only 35% (8/23) of those with self-reported PCOS actually
      fulfilled the NIH criteria for PCOS. Comorbidities were relatively similar among
      groups. Finally, approximately 65% (15/23) were unhappy or worried about their
      initial PCOS diagnosis, with 72% (13/18) stating fertility concerns were the most
      distressing aspect of their diagnosis. CONCLUSIONS: The lack of consistent and
      accurate diagnosis of PCOS in young women potentially leads to over-diagnosis.
      This creates unnecessary fears of health complications, particularly infertility.
      Therefore, we recommend the development of standardised criteria with set
      parameters that allow for better diagnosis of PCOS.

PMID- 29052217
TI  - The comings and goings of the vagus and the need to know your neural fulcrum.

PMID- 29052218
TI  - New evidence for association of recessive IARS gene mutations with hepatopathy,
      hypotonia, intellectual disability and growth retardation.

PMID- 29052219
TI  - Pharmacogenomic Discovery to Function and Mechanism: Breast Cancer as a Case
      Study.
AB  - Biomedical research is undergoing rapid change, with the development of a series
      of analytical omics techniques that are capable of generating Biomedical Big
      Data. These developments provide an unprecedented opportunity to gain novel
      insight into disease pathophysiology and mechanisms of drug action and response
      but they also present significant challenges. Pharmacogenomics is a discipline
      within Clinical Pharmacology that has been at the forefront in defining, taking
      advantage of, and dealing with the opportunities and challenges of this aspect of
      the Post-Genome Project world. This overview will describe the evolution of
      germline pharmacogenomic research strategies as we have moved from an era of
      candidate genes to agnostic genome-wide association studies (GWAS) coupled with
      the functional and mechanistic pursuit of GWAS signals. Germline pharmacogenomic
      studies of breast cancer endocrine therapy will be used to illustrate research
      strategies that are being applied broadly to omics studies of drug response
      phenotypes.

PMID- 29052220
TI  - Efficacy From Strange Sources.
AB  - Reverse translation (RT) refers to perceptions and observations of clinical
      outcomes, both beneficial and harmful, that can lead to a hypothesis intended to
      identify a new use of a drug that is different from the original use. I provide a
      panoramic view of successes in RT from the historic discovery of penicillin to
      the contemporary development of CAR (chimeric antigen receptor) T therapies. I
      delineate the core principles of RT that shift discovery from serendipity to a
      systematic strategy based on target identification and causal biology,
      pharmacodynamic biomarkers that recapitulate disease pathophysiology,
      confirmation of target engagement by clinical proof of concept studies, and
      optimal selection of dose and interval. The article proposes four different
      categories of RT and successful examples are provided for each category. It
      concludes with a summary of open questions related to the business case of RT
      that includes a comparison of the pros, cons, and barriers to future RT
      development programs.

PMID- 29052221
TI  - Advance in physiologically based pharmacokinetic modelling: from the organ level
      to suborgan level based on experimental data.

PMID- 29052222
TI  - The migrant crisis comes to Minnesota: a dermatologist's perspective.

PMID- 29052223
TI  - Identification of four novel RHD alleles by weakened antigen D expression.

PMID- 29052224
TI  - Opiate Prescribing in Hospitalized Older Adults: Patterns and Outcomes.
AB  - BACKGROUND/OBJECTIVES: Whereas opiate prescribing patterns have been well
      described in outpatient and emergency department settings, they have been less
      defined in hospitalized older adults. The objective was to describe patterns of
      opiate prescribing and associated outcomes in hospitalized older adults. DESIGN:
      Retrospective cohort study. SETTING: Tertiary care facility. PARTICIPANTS:
      Hospitalized medical patients aged 65 and older (N = 9,245; mean age 80.3, 55.2%
      female, 72.3% white, 90.8% non-Hispanic). MEASUREMENTS: Opiate exposure and
      duration of action, concurrent use of potentially inappropriate medications
      (PIMs), adverse events, discharge disposition, length of stay (LOS), and 30-day
      readmissions. RESULTS: There was no difference in sex, race, ethnicity, or
      Charlson Comorbidity Index between opiate exposure groups. Participants who had
      never received opiates had a significantly shorter mean LOS than prior and new
      opiate users (5.2, 6.8, 7.7 days; P < .001) and were more likely to be discharged
      home (88.6%, 82.8%, 82.5%; P < .001) and significantly less likely to be
      readmitted within 30-days (19.6%, 25.0%, 22.3%; P < .001). Participant who had
      never been exposed to opiates had a significantly shorter mean LOS than those
      receiving short- and long-acting opiates (5.2, 7.3, 8.6 days; P < .001) and were
      more likely to be discharged home (88.6%, 82.6%, 82.4%; P < .001) and
      significantly less likely to be readmitted within 30-days (19.6%, 27.7%, 28.9%; P
      < .001). CONCLUSION: Opiate use is widespread during hospitalization and is
      associated with significant negative clinical outcomes and quality metrics. There
      is an urgent need to develop innovative pain management alternatives to opiate
      use.

PMID- 29052225
TI  - Peripheral nerve block in ankle fracture surgery: a qualitative study of
      patients' experiences.
AB  - Peripheral nerve blocks are popular as a mode of anaesthesia for limb surgery and
      their beneficial effects are well documented in elective surgery. However,
      concerns have been raised about potential rebound pain outweighing the benefits
      in acute ankle fracture surgery. Furthermore, pain scores and morphine
      consumption do not provide a full picture, as pain is subjective. To evaluate the
      clinical usefulness of peripheral nerve blocks, we explored patients'
      expectations and experiences by means of semi-structured interviews analysed with
      systematic text condensation. We obtained ethical approval and informed consent
      and sampled purposively among adult patients scheduled for ankle surgery with
      nerve blocks as the primary mode of anaesthesia. Patients were interviewed within
      48 h postoperatively. Data saturation was reached after 13 interviews. We found
      that, despite pre-emptive ibuprofen and paracetamol, some patients did experience
      excruciating rebound pain for up to 2 h, although most had little or no pain. The
      patients had doubts about what to do when the block wore off, which led to a risk
      of unnecessary pain levels or morphine overuse. Patients had difficulty
      understanding the effect and course of the nerve blocks. They had
      misunderstandings regarding the blocks' effect on sensation, resulting in fear of
      feeling pain during surgery and of permanent nerve damage after surgery. However,
      patients valued the mental alertness, ability to ambulate and efficient pain
      relief provided by the blocks. We recommend that patients be given thorough and
      repeated information as we feel this is crucial in preventing undesirable
      responses from patients, and is likely to increase the overall clinical
      usefulness of nerve blocks in acute limb surgery.

PMID- 29052226
TI  - Translational High-Dimensional Drug Interaction Discovery and Validation Using
      Health Record Databases and Pharmacokinetics Models.
AB  - Polypharmacy increases the risk of drug-drug interactions (DDIs). Combining
      epidemiological studies with pharmacokinetic modeling, we detected and evaluated
      high-dimensional DDIs among 30 frequent drugs. Multidrug combinations that
      increased the risk of myopathy were identified in the US Food and Drug
      Administration Adverse Event Reporting System (FAERS) and electronic medical
      record (EMR) databases by a mixture drug-count response model. CYP450 inhibition
      was estimated among the 30 drugs in the presence of 1 to 4 inhibitors using in
      vitro / in vivo extrapolation. Twenty-eight three-way and 43 four-way DDIs had
      significant myopathy risk in both databases and predicted increases in the area
      under the concentration-time curve ratio (AUCR) >2-fold. The high-dimensional DDI
      of omeprazole, fluconazole, and clonidine was associated with a 6.41-fold (FAERS)
      and 18.46-fold (EMR) increased risk of myopathy local false discovery rate
      (<0.005); the AUCR of omeprazole in this combination was 9.35. The combination of
      health record informatics and pharmacokinetic modeling is a powerful
      translational approach to detect high-dimensional DDIs.

PMID- 29052228
TI  - Symptoms of depression in Swedish fathers in the postnatal period and development
      of a screening tool.
AB  - Methods for detecting depression in fathers after the birth of their child are
      scarce. The Edinburgh Postnatal Depression Scale (EPDS), used to screen mothers
      for postpartum depression (PPD), lacks somatization and externalizing items. This
      potentially decreases its sensitivity in detecting depression in fathers, as many
      men actually express depression with somatization or externalizing symptoms. The
      present study assessed depressive symptoms in fathers of children 0-18 months
      old, and evaluated whether addressing both typical depression and externalizing,
      so-called "depressive equivalent" symptoms, might be more suitable for such
      assessment. The Beck Depression Inventory-II (BDI-II), EPDS, and Gotland Male
      Depression Scale (GMDS) were responded to by 447 Swedish fathers online. Among
      participants, 27% reported depressive symptoms above the BDI-II cut-off
      suggestive of depression. Most fathers reported both traditional and depressive
      equivalent symptoms and a subgroup expressed exclusively depressive equivalent
      symptoms. Consistently, a scale combining items from the EPDS and GMDS showed
      higher sensitivity than the EPDS alone in identifying fathers with elevated
      depressive symptoms, at equal levels of specificity. Our findings suggest that a
      combination of EPDS and depressive equivalent symptom items results in a more
      suitable instrument for screening for depression in fathers during the postnatal
      period.

PMID- 29052229
TI  - Erratum: Agerinia smithorum sp. nov., a new early Eocene primate from the Iberian
      Peninsula; 161: 116-124. Joan Femenias-Gual, Raef Minwer-Barakat, Judit Marigo
      and Salvador Moya-Sola. DOI: 10.1002/ajpa.23014.

PMID- 29052227
TI  - Adjuvant pretreatment with alum protects neonatal mice in sepsis through myeloid
      cell activation.
AB  - The high mortality in neonatal sepsis has been related to both quantitative and
      qualitative differences in host protective immunity. Pretreatment strategies to
      prevent sepsis have received inadequate consideration, especially in the
      premature neonate, where outcomes from sepsis are so dismal. Aluminium salts
      based adjuvants (alum) are used currently in many paediatric vaccines, but their
      use as an innate immune stimulant alone has not been well studied. We asked
      whether pretreatment with alum adjuvant alone could improve outcome and host
      innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum
      pretreatment improves survival to polymicrobial sepsis in both wild-type and T
      and B cell-deficient neonatal mice, but not in caspase-1/11 null mice. Moreover,
      alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases
      bacterial colonization in the peritoneum. Bone marrow-derived neutrophils from
      alum-pretreated neonates produce more neutrophil extracellular traps (NETs) and
      exhibit increased expression of neutrophil elastase (NE) after in-vitro
      stimulation with phorbol esters. In addition, alum pretreatment increases bone
      marrow and splenic haematopoietic stem cell expansion following sepsis.
      Pretreatment of neonatal mice with an alum-based adjuvant can stimulate multiple
      innate immune cell functions and improve survival. These novel findings suggest a
      therapeutic pathway for the use of existing alum-based adjuvants for preventing
      sepsis in premature infants.

PMID- 29052230
TI  - Omecamtiv mercabil and blebbistatin modulate cardiac contractility by perturbing
      the regulatory state of the myosin filament.
AB  - KEY POINTS: Omecamtiv mecarbil and blebbistatin perturb the regulatory state of
      the thick filament in heart muscle. Omecamtiv mecarbil increases contractility at
      low levels of activation by stabilizing the ON state of the thick filament.
      Omecamtiv mecarbil decreases contractility at high levels of activation by
      disrupting the acto-myosin ATPase cycle. Blebbistatin reduces contractility by
      stabilizing the thick filament OFF state and inhibiting acto-myosin ATPase. Thick
      filament regulation is a promising target for novel therapeutics in heart
      disease. ABSTRACT: Contraction of heart muscle is triggered by a transient rise
      in intracellular free calcium concentration linked to a change in the structure
      of the actin-containing thin filaments that allows the head or motor domains of
      myosin from the thick filaments to bind to them and induce filament sliding. It
      is becoming increasingly clear that cardiac contractility is also regulated
      through structural changes in the thick filaments, although the molecular
      mechanisms underlying thick filament regulation are still relatively poorly
      understood. Here we investigated those mechanisms using small molecules -
      omecamtiv mecarbil (OM) and blebbistatin (BS) - that bind specifically to myosin
      and respectively activate or inhibit contractility in demembranated cardiac
      muscle cells. We measured isometric force and ATP utilization at different
      calcium and small-molecule concentrations in parallel with in situ structural
      changes determined using fluorescent probes on the myosin regulatory light chain
      in the thick filaments and on troponin C in the thin filaments. The results show
      that BS inhibits contractility and actin-myosin ATPase by stabilizing the OFF
      state of the thick filament in which myosin head domains are more parallel to the
      filament axis. In contrast, OM stabilizes the ON state of the thick filament, but
      inhibits contractility at high intracellular calcium concentration by disrupting
      the actin-myosin ATPase pathway. The effects of BS and OM on the calcium
      sensitivity of isometric force and filament structural changes suggest that the
      co-operativity of calcium activation in physiological conditions is due to
      positive coupling between the regulatory states of the thin and thick filaments.

PMID- 29052232
TI  - Different functional genes of upper airway microbiome associated with natural
      course of childhood asthma.
AB  - BACKGROUND: Microbial colonization of the airway plays a role in the pathogenesis
      of asthma; however, the effect of the upper airway microbiome on childhood asthma
      is not fully understood. We analyzed the metagenome of airway microbiome to
      understand the associated role of upper airway microbiome with the natural course
      of childhood asthma. METHODS: Nasopharyngeal swabs were collected from children
      with asthma, those in asthma remission, and control groups. High-throughput
      sequencing was used to examine the structure and functional dynamics of the
      airway microbiome with respect to asthma phenotypes. RESULTS: The composition of
      microbiota differed among healthy control, asthma, and remission groups. The
      relative abundance of Streptococcus was negatively associated with FEV1%
      predicted (P = .023) and that of Staphylococcus was negatively associated with
      methacholine PC20 (P = .013). Genes related to arachidonic acid metabolites,
      lysine residues, and glycosaminoglycans in the microbiome could be associated
      with airway inflammation. In particular, genes related to synthesis of anti
      inflammatory prostaglandin E2 (PGE2 ) were not detected from the airway
      microbiome in the asthma group. CONCLUSIONS: These data suggest that alterations
      in the composition and function of the upper airway microbiome could be related
      with the natural course of asthma in children.

PMID- 29052231
TI  - Audit of appropriate use of platelet transfusions: validation of adjudication
      criteria.
AB  - BACKGROUND AND OBJECTIVES: Platelet (PLT) transfusions must be used
      appropriately, as they are in chronic short supply, costly and risky to patients.
      The goals of this audit were to: (1) validate preset adjudication criteria
      through an audit of appropriateness at four large academic hospitals; (2)
      identify variability in appropriateness across medical services, physician
      specialties or hospital locations; and (3) inform logistical or educational
      interventions that may reduce inappropriate use. MATERIALS AND METHODS: A chart
      review of two hundred patients receiving PLT transfusions was performed. Fifty
      consecutive transfusion episodes per site were audited in detail. Each
      transfusion episode was independently adjudicated as appropriate or inappropriate
      by two transfusion specialists based on predetermined criteria. RESULTS: The
      adjudication criteria performed well with simple agreement of 95% (kappa
      statistic 0.83) between reviewers. Overall, 78% (95% CI: 72-84%) of PLT
      transfusions were adjudicated as appropriate, with results varying significantly
      by hospital site (range 62-94%). Prophylactic transfusions for non-bleeding
      patients had the highest proportion of appropriateness (85%, n = 80), and
      therapeutic transfusions for bleeding patients had the lowest (73%, n = 99). The
      lowest levels of appropriate platelet transfusions were observed in the operating
      rooms (60%) and when ordered by the general surgery service (55%). CONCLUSIONS:
      One in five platelet transfusions may be unnecessary, suggesting that
      interventions to improve PLT transfusion practice are warranted.

PMID- 29052233
TI  - Heterogeneous expression of glycoconjugates in the primary olfactory centre of
      the Japanese sword-tailed newt (Cynops ensicauda).
AB  - Histochemical organization of the Caudata olfactory system remains largely
      unknown, despite this amphibian order showing phylogenetic diversity in the
      development of the vomeronasal organ and its primary centre, the accessory
      olfactory bulb. Here, we investigated the glycoconjugate distribution in the
      olfactory bulb of a semi-aquatic salamander, the Japanese sword-tailed newt
      (Cynops ensicauda), by histochemical analysis of the lectins that were present.
      Eleven lectins showed a specific binding to the olfactory and vomeronasal nerves
      as well as to the olfactory glomeruli. Among them, succinylated wheat germ
      agglutinin (s-WGA), soya bean agglutinin (SBA), Bandeiraea simplicifolia lectin-I
      (BSL-I) and peanut agglutinin showed significantly different bindings to
      glomeruli between the main and accessory olfactory bulbs. We also found that s
      WGA, SBA, BSL-I and Pisum sativum agglutinin preferentially bound to a rostral
      cluster of glomeruli in the main olfactory bulb. This finding suggests the
      presence of a functional subset of primary projections to the main olfactory
      system. Our results therefore demonstrated a region-specific glycoconjugate
      expression in the olfactory bulb of C. ensicauda, which would be related to a
      functional segregation of the olfactory system.

PMID- 29052234
TI  - Measuring precision in bioassays: Rethinking assay validation.
AB  - The m:n:thetab procedure is often used for validating an assay for precision,
      where m levels of an analyte are measured with n replicates at each level, and if
      all m estimates of coefficient of variation (CV) are less than thetab , then the
      assay is declared validated for precision. The statistical properties of the
      procedure are unknown so there is no clear statistical statement of precision
      upon passing. Further, it is unclear how to modify the procedure for relative
      potency assays in which the constant standard deviation (SD) model fits much
      better than the traditional constant CV model. We use simple normal error models
      to show that under constant CV across the m levels, the probability of passing
      when the CV is thetab is about 10% to 20% for some recommended implementations;
      however, for extreme heterogeniety of CV when the largest CV is thetab , the
      passing probability can be greater than 50%. We derive 100q% upper confidence
      limits on the CV under constant CV models and derive analogous limits for the SD
      under a constant SD model. Additionally, for a post-validation assay output of y,
      we derive 68.27% confidence intervals on either the mean or log geometric mean of
      the assay output using either y+/-s (for the constant SD model) or log(y)+/-rG
      (for the constant CV model), where s and rG are constants that do not depend on
      y. We demonstrate the methods on a growth inhibition assay used to measure
      biologic activity of antibodies against the malaria parasite.

PMID- 29052235
TI  - Establishment of a markerless multiple-gene deletion method based on Cre/loxP
      mutant system for Bacillus pumilus.
AB  - In this study, we established a Cre/loxP mutant recombination system (Cre/lox71
      66 system) for markerless gene deletion to facilitate our follow-up rational
      genetic engineering to the strain Bacillus pumilus W3. This modified method uses
      two mutant loxP sites, which after recombination creates a double-mutant loxP
      site that is poorly recognized by Cre recombinase, facilitating multiple gene
      deletions in a single genetic background. Two selected genes, cotA and sigF, were
      continuously knocked out and verified at different levels using this method. This
      method is simple and efficient and can be easily implemented for multiple gene
      deletions in B. pumilus.

PMID- 29052236
TI  - Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a
      MADIT-RIT substudy.
AB  - BACKGROUND: The effects of heart failure (HF) severity on risk of inappropriate
      implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly
      investigated. We aimed to study the association between HF severity and
      inappropriate ICD therapy in MADIT-RIT. METHODS: MADIT-RIT randomized 1,500
      patients to three ICD programming arms: conventional (Arm A), high-rate cut-off
      (Arm B: >=200 beats/min), and delayed therapy (Arm C: 60-second delay for >=170
      beats/min). We evaluated the association between New York Heart Association
      (NYHA) class III (n = 256) versus class I-II (n = 251) and inappropriate ICD
      therapy in Arm A patients with ICD-only and cardiac resynchronization therapy
      with defibrillator (CRT-D). We additionally assessed benefit of novel ICD
      programming in Arms B and C versus Arm A by NYHA classification. RESULTS: In Arm
      A, the risk of inappropriate therapy was significantly higher in those with NYHA
      III versus NYHA I-II for both ICD (hazard ratio [HR] = 2.55, confidence interval
      [CI]: 1.51-4.30, P < 0.001) and CRT-D patients (HR = 3.73, CI: 1.14-12.23, P =
      0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy <
      200 beats/min, but not for inappropriate shocks. Novel ICD programming
      significantly reduced inappropriate therapy in patients with both NYHA III (Arm B
      vs Arm A: HR = 0.08, P < 0.001; Arm C vs Arm A: HR = 0.17, P < 0.001) and NYHA I
      II (Arm B vs Arm A: HR = 0.25, P < 0.001; Arm C vs Arm A: HR = 0.28, P < 0.001).
      CONCLUSION: Patients with more severe HF are at increased risk for inappropriate
      ICD therapy, particularly ATP due to arrhythmias < 200 beats/min. Novel
      programming with high-rate cut-off or delayed detection reduces inappropriate ICD
      therapies in both mild and moderate HF.

PMID- 29052238
TI  - Frequent expression of CD30 in extranodal NK/T-cell lymphoma: Potential
      therapeutic target for anti-CD30 antibody-based therapy.
AB  - Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is a subtype of non-Hodgkin
      lymphoma with a poor prognosis. Although first-line treatments for patients with
      localized ENKTL have been established, there is no gold standard treatment for
      patients with advanced ENKTL and refractory and/or relapsed disease. Anti-CD30
      antibody-based therapy, including brentuximab vedotin (BV), has been shown to
      target malignant lymphomas with CD30 expression. In particular, this therapeutic
      agent has recently been suggested to be effective for Hodgkin lymphoma and mature
      T-cell lymphoma. However, the efficacy of BV toward ENKTL has not yet been
      established. Therefore, we investigated the expression of CD30 in a large cohort
      to evaluate BV as a potential treatment for ENKTL. In this study, 97 Japanese
      patients with newly diagnosed ENKTL between January 2007 and December 2015 were
      enrolled. Flow cytometry and immunohistochemistry were performed for the
      evaluation of CD30 expression. If the cut-off value of CD30 expression is 1% or
      more, there were 55 positive cases (56.5%). According to the localization of
      lesion, the frequency of CD30 expression was significantly higher in the non
      nasal type than in the nasal type (P = .0394). No differences were observed in
      almost all clinical characteristics between CD30-positive cases and CD30-negative
      cases. In addition, the expression of CD30 was not a prognostic factor for either
      overall survival or progression-free survival. In conclusion, frequent expression
      of CD30 in ENKTL suggests anti-CD30 antibody-based therapy may be an effective
      treatment.

PMID- 29052237
TI  - The taxonomic composition of the donor intestinal microbiota is a major factor
      influencing the efficacy of faecal microbiota transplantation in therapy
      refractory ulcerative colitis.
AB  - BACKGROUND: Faecal microbiota transplantation is an experimental approach for the
      treatment of patients with ulcerative colitis. Although there is growing evidence
      that faecal microbiota transplantation is effective in this disease, factors
      affecting its response are unknown. AIMS: To establish a faecal microbiota
      transplantation treatment protocol in ulcerative colitis patients, and to
      investigate which patient or donor factors are responsible for the treatment
      success. METHODS: This is an open controlled trial of repeated faecal microbiota
      transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic
      pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis
      patients over 90 days. Faecal samples of donors and patients were analysed by
      16SrRNA gene-based microbiota analysis. RESULTS: In the FMT-group, 10/17 (59%) of
      patients showed a response and 4/17 (24%) a remission to faecal microbiota
      transplantation. Response to faecal microbiota transplantation was mainly
      influenced by the taxonomic composition of the donor's microbiota. Stool of
      donors with a high bacterial richness (observed species remission 946 +/- 93 vs
      no response 797 +/- 181 at 15367 rps) and a high relative abundance of
      Akkermansia muciniphila (3.3 +/- 3.1% vs 0.1 +/- 0.2%), unclassified
      Ruminococcaceae (13.8 +/- 5.0% vs 7.5 +/- 3.7%), and Ruminococcus spp. (4.9 +/-
      3.5% vs 1.0 +/- 0.7%) were more likely to induce remission. In contrast
      antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a
      sustained decrease of intestinal microbial richness. CONCLUSIONS: The taxonomic
      composition of the donor's intestinal microbiota is a major factor influencing
      the efficacy of faecal microbiota transplantation in ulcerative colitis patients.
      The design of specific microbial preparation might lead to new treatments for
      ulcerative colitis.

PMID- 29052239
TI  - Three-part joint modeling methods for complex functional data mixed with zero-and
      one-inflated proportions and zero-inflated continuous outcomes with skewness.
AB  - We take a functional data approach to longitudinal studies with complex bivariate
      outcomes. This work is motivated by data from a physical activity study that
      measured 2 responses over time in 5-minute intervals. One response is the
      proportion of time active in each interval, a continuous proportions with excess
      zeros and ones. The other response, energy expenditure rate in the interval, is a
      continuous variable with excess zeros and skewness. This outcome is complex
      because there are 3 possible activity patterns in each interval (inactive,
      partially active, and completely active), and those patterns, which are observed,
      induce both nonrandom and random associations between the responses. More
      specifically, the inactive pattern requires a zero value in both the proportion
      for active behavior and the energy expenditure rate; a partially active pattern
      means that the proportion of activity is strictly between zero and one and that
      the energy expenditure rate is greater than zero and likely to be moderate, and
      the completely active pattern means that the proportion of activity is exactly
      one, and the energy expenditure rate is greater than zero and likely to be
      higher. To address these challenges, we propose a 3-part functional data joint
      modeling approach. The first part is a continuation-ratio model to reorder the
      ordinal valued 3 activity patterns. The second part models the proportions when
      they are in interval (0,1). The last component specifies the skewed continuous
      energy expenditure rate with Box-Cox transformations when they are greater than
      zero. In this 3-part model, the regression structures are specified as smooth
      curves measured at various time points with random effects that have a
      correlation structure. The smoothed random curves for each variable are
      summarized using a few important principal components, and the association of the
      3 longitudinal components is modeled through the association of the principal
      component scores. The difficulties in handling the ordinal and proportional
      variables are addressed using a quasi-likelihood type approximation. We develop
      an efficient algorithm to fit the model that also involves the selection of the
      number of principal components. The method is applied to physical activity data
      and is evaluated empirically by a simulation study.

PMID- 29052240
TI  - Testing predictions of the emotion regulation model of binge-eating disorder.
AB  - OBJECTIVE: The emotion regulation (ER) model of binge eating posits that
      individuals with binge-eating disorder (BED) experience more intense emotions and
      greater difficulties in ER than individuals without BED, leading them to binge
      eat as a means of regulating emotions. According to this model, individuals with
      BED should report greater difficulties in ER than their non-BED counterparts, the
      severity of these difficulties should be positively associated with BED symptoms,
      and this association should be stronger when individuals experience persistent
      negative emotions (i.e., depression). Studies examining these hypotheses,
      however, have been limited. METHOD: Data were collected from adults meeting the
      DSM 5 criteria for BED (n = 71; 93% female) and no history of an eating disorder
      (NED; n =  79; 83.5% female). Participants completed self-report measures of
      difficulties in ER, eating disorder (ED) psychopathology, and depression.
      RESULTS: Individuals with BED reported greater difficulties in ER compared to
      those with NED. Moreover, difficulties in ER predicted unique variance in binge
      frequency and ED psychopathology in BED. Depression moderated the association
      between ER difficulties and binge frequency such that emotion dysregulation and
      binge frequency were positively associated in those reporting high, but not low,
      depression levels. DISCUSSION: The association between difficulties in ER and ED
      pathology in BED suggests that treatments focusing on improving ER skills may be
      effective in treating this ED; however, the moderating effect of depression
      underscores the need for research on individual differences and treatment
      moderators. These findings suggest the importance of ER in understanding and
      treating BED.

PMID- 29052241
TI  - Symbol Grounding Without Direct Experience: Do Words Inherit Sensorimotor
      Activation From Purely Linguistic Context?
AB  - Theories of embodied cognition assume that concepts are grounded in non
      linguistic, sensorimotor experience. In support of this assumption, previous
      studies have shown that upwards response movements are faster than downwards
      movements after participants have been presented with words whose referents are
      typically located in the upper vertical space (and vice versa for downwards
      responses). This is taken as evidence that processing these words reactivates
      sensorimotor experiential traces. This congruency effect was also found for novel
      words, after participants learned these words as labels for novel objects that
      they encountered either in their upper or lower visual field. While this
      indicates that direct experience with a word's referent is sufficient to evoke
      said congruency effects, the present study investigates whether this direct
      experience is also a necessary condition. To this end, we conducted five
      experiments in which participants learned novel words from purely linguistic
      input: Novel words were presented in pairs with real up- or down-words
      (Experiment 1); they were presented in natural sentences where they replaced
      these real words (Experiment 2); they were presented as new labels for these real
      words (Experiment 3); and they were presented as labels for novel combined
      concepts based on these real words (Experiment 4 and 5). In all five experiments,
      we did not find any congruency effects elicited by the novel words; however,
      participants were always able to make correct explicit judgements about the
      vertical dimension associated to the novel words. These results suggest that
      direct experience is necessary for reactivating experiential traces, but this
      reactivation is not a necessary condition for understanding (in the sense of
      storing and accessing) the corresponding aspects of word meaning.

PMID- 29052242
TI  - Emerging infectious disease outbreaks: estimating disease risk in Australian
      blood donors travelling overseas.
AB  - BACKGROUND AND OBJECTIVES: International travel assists spread of infectious
      pathogens. Australians regularly travel to South-eastern Asia and the isles of
      the South Pacific, where they may become infected with infectious agents, such as
      dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses that pose a potential
      risk to transfusion safety. In Australia, donors are temporarily restricted from
      donating for fresh component manufacture following travel to many countries,
      including those in this study. We aimed to estimate the unmitigated transfusion
      transmission (TT) risk from donors travelling internationally to areas affected
      by emerging infectious diseases. MATERIALS AND METHODS: We used the European Up
      Front Risk Assessment Tool, with travel and notification data, to estimate the TT
      risk from donors travelling to areas affected by disease outbreaks: Fiji (DENV),
      Bali (DENV), Phuket (DENV), Indonesia (CHIKV) and French Polynesia (ZIKV).
      RESULTS: We predict minimal risk from travel, with the annual unmitigated risk of
      an infected component being released varying from 1 in 1.43 million to <1 in one
      billion and the risk of severe consequences ranging from 1 in 130 million to <1
      in one billion. CONCLUSION: The predicted unmitigated likelihood of infection in
      blood components manufactured from donors travelling to the above-mentioned areas
      was very low, with the possibility of severe consequences in a transfusion
      recipient even smaller. Given the increasing demand for plasma products in
      Australia, the current strategy of restricting donors returning from select
      infectious disease outbreak areas to source plasma collection provides a simple
      and effective risk management approach.

PMID- 29052243
TI  - Wnt/beta-catenin signalling pathway mediated aberrant hippocampal neurogenesis in
      kainic acid-induced epilepsy.
AB  - Temporal lobe epilepsy is a chronic disorder of nerve system, mainly
      characterized by hippocampal sclerosis with massive neuronal loss and severe
      gliosis. Aberrant neurogenesis has been shown in the epileptogenesis process of
      temporal lobe epilepsy. However, the molecular mechanisms underlying aberrant
      neurogenesis remain unclear. The roles of Wnt signalling cascade have been well
      established in neurogenesis during multiple aspects. Here, we used kainic acid
      induced rat epilepsy model to investigate whether Wnt/beta-catenin signalling
      pathway is involved in the aberrant neurogenesis in temporal lobe epilepsy.
      Immunostaining and western blotting results showed that the expression levels of
      beta-catenin, Wnt3a, and cyclin D1, the key regulators in Wnt signalling pathway,
      were up-regulated during acute epilepsy induced by the injection of kainic acids,
      indicating that Wnt signalling pathway was activated in kainic acid-induced
      temporal lobe epilepsy. Moreover, BrdU labelling results showed that blockade of
      the Wnt signalling by knocking down beta-catenin attenuated aberrant neurogenesis
      induced by kainic acids injection. Altogether, Wnt/beta-catenin signalling
      pathway mediated hippocampal neurogenesis during epilepsy, which might provide
      new strategies for clinical treatment of temporal lobe epilepsy. Temporal lobe
      epilepsy is a chronic disorder of nerve system, mainly characterized by
      hippocampal sclerosis. Aberrant neurogenesis has been shown to involve in the
      epileptogenesis process of temporal lobe epilepsy. In the present study, we
      discovered that Wnt3a/beta-catenin signalling pathway serves as a link between
      aberrant neurogenesis and underlying remodelling in the hippocampus, leading to
      temporal lobe epilepsy, which might provide new strategies for clinical treatment
      of temporal lobe epilepsy.

PMID- 29052244
TI  - Prompt detection of L-asparaginase inactivation is crucial to optimize treatment
      efficacy also in aggressive lymphomas.

PMID- 29052245
TI  - The longitudinal impact of probiotic and peanut oral immunotherapy on health
      related quality of life.
AB  - BACKGROUND: We previously reported that probiotic and peanut oral immunotherapy
      (PPOIT) was effective at inducing sustained unresponsiveness compared with
      placebo in a double-blind, placebo-controlled randomized trial. This study
      evaluated the impact of PPOIT on health-related quality of life (HRQL). METHOD:
      Fifty-one participants (PPOIT 24; placebo 27) from the PPOIT trial completed Food
      Allergy Quality of Life Questionnaire (FAQLQ-PF) and Food Allergy Independent
      Measure (FAIM) at pre-treatment, end-of-treatment and 3 months after end-of
      treatment. A total of 42 participants (20 PPOIT; 22 placebo) completed measures
      at 12 months post-treatment. Changes over time in PPOIT and placebo groups were
      examined by repeated-measures analysis of variance and paired t tests. RESULTS:
      Probiotic and peanut oral immunotherapy was associated with significant
      improvement in FAQLQ-PF (F = 3.63, P = .02), with mean difference 0.8 at 3 months
      post-treatment (P = .05) and 1.3 at 12 months post-treatment (P = .005),
      exceeding the 0.5 minimal clinically important difference for FAQLQ-PF. For FAIM,
      mean difference was 0.5 (P = .03) at 3 months and 0.4 (P = .04) at 12 months post
      treatment. In placebo group, post-treatment FAQLQ and FAIM remained unchanged
      from pretreatment. Improvement in FAQLQ-PF and FAIM scores related specifically
      to acquisition of sustained unresponsiveness rather than to receiving PPOIT
      treatment or participation in the trial. CONCLUSIONS: Probiotic and peanut oral
      immunotherapy has a sustained beneficial effect on psychosocial impact of food
      allergy at 3 and 12 months after end-of-treatment. Treatment was not associated
      with reduced HRQL relative to baseline in either PPOIT or placebo groups,
      indicating that PPOIT was well tolerated and psychological well-being was not
      negatively impacted. Improved HRQL was specifically associated with acquisition
      of sustained unresponsiveness.

PMID- 29052246
TI  - Food protein-induced enterocolitis syndrome by fish: Not necessarily a restricted
      diet.
AB  - Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated
      gastrointestinal food hypersensitivity usually due to cow's milk or soy. Recent
      researches show that fish is 1 of the most important triggers of FPIES in the
      Mediterranean countries. Due to the risk of multiple-food FPIES, avoiding foods
      in the same category or that often occur together may be reasonable. The aim of
      this study was to evaluate the evolution and follow-up of FPIES related to fish
      over a period of 20 years. We describe the clinical features of our population,
      discuss different approaches to oral food challenges, and analyze the possibility
      of introducing the culprit fish or other nonrelated fish to avoid unnecessary
      restricted diets.

PMID- 29052247
TI  - Meta-analysis approaches to combine multiple gene set enrichment studies.
AB  - In the field of gene set enrichment analysis (GSEA), meta-analysis has been used
      to integrate information from multiple studies to present a reliable
      summarization of the expanding volume of individual biomedical research, as well
      as improve the power of detecting essential gene sets involved in complex human
      diseases. However, existing methods, Meta-Analysis for Pathway Enrichment (MAPE),
      may be subject to power loss because of (1) using gross summary statistics for
      combining end results from component studies and (2) using enrichment scores
      whose distributions depend on the set sizes. In this paper, we adapt meta
      analysis approaches recently developed for genome-wide association studies, which
      are based on fixed effect and random effects (RE) models, to integrate multiple
      GSEA studies. We further develop a mixed strategy via adaptive testing for
      choosing RE versus FE models to achieve greater statistical efficiency as well as
      flexibility. In addition, a size-adjusted enrichment score based on a one-sided
      Kolmogorov-Smirnov statistic is proposed to formally account for varying set
      sizes when testing multiple gene sets. Our methods tend to have much better
      performance than the MAPE methods and can be applied to both discrete and
      continuous phenotypes. Specifically, the performance of the adaptive testing
      method seems to be the most stable in general situations.

PMID- 29052248
TI  - Comparative anatomical study of sound production and reception systems in the
      common dolphin (Delphinus delphis) and the harbour porpoise (Phocoena phocoena)
      heads.
AB  - Magnetic resonance imaging (MRI) and computed tomography (CT) scans were used to
      analyse, respectively, the soft tissues and the bones of the heads of four common
      dolphins and three harbour porpoises. This imaging study was completed by an
      examination of anatomical sections performed on two odontocete heads (a subadult
      common dolphin and a subadult harbour porpoise). The three complementary
      approaches allowed to illustrate anatomical differences in the echolocation
      systems of the common dolphin and the harbour porpoise. We captured images
      confirming strong differences of symmetry of the melon and of its connexions to
      the MLDB (Monkeys Lips/Dorsal Bursae) between the common dolphin and the harbour
      porpoise. The melon of the common dolphin is asymmetrically directly connected to
      the right bursae cantantes at its right side, whereas the melon of the harbour
      porpoise is symmetrical, and separated from the two bursae cantantes by a set of
      connective tissues. Another striking difference comes from the bursae cantantes
      themselves, less deeply located in the head of the common dolphin than in the
      harbour porpoise.

PMID- 29052249
TI  - Image noise reduction technology allows significant reduction of radiation dosage
      in cardiac device implantation procedures.
AB  - BACKGROUND: Novel x-ray systems with real-time image noise reduction technology
      (INRT) to reduce radiation dose during fluoroscopy and cine acquisition have
      become available. This study evaluated the reduction of radiation dose in device
      implantation with INRT. METHODS: Radiation dose data from 132 consecutive new
      device implantation procedures (102 pacemaker [PM] or implantable cardioverter
      defibrillator [ICD] and 30 cardiac resynchronization therapy [CRT] devices)
      performed between January 2015 and December 2015 on an angiography system with
      INRT (Allura ClarityIQ) were collected. For comparison, radiation dose data from
      147 consecutive device implantation procedures (121 PM/ICDs and 26 CRT devices)
      performed between June 2013 and September 2014 on a C-arm system with continuous
      and pulsed fluoroscopy option (4 frames/second) were evaluated. Total dose area
      product (DAP), fluoroscopy DAP, and cine DAP were evaluated. RESULTS: Patient
      age, gender and body weight, procedure, and fluoroscopy times were similar
      between systems. In PM/ICD cases, DAP of INRT and C-arm system was similar (423
      +/- 381 cGycm2  vs 417 +/- 517 cGycm) due to pulsed fluoroscopy with the C-arm
      system (78% of time) and sparse use of cine. In CRT procedures requiring higher
      image quality (82% use of continuous fluoroscopy with C-arm system), DAP of INRT
      was significantly lower (1,544 +/- 834 cGycm vs 7,252 +/- 6,431 cGycm, P < 0.001)
      due to less fluoroscopy DAP (1,414 +/- 757 cGycm vs 5,854 +/- 6,767 cGycm) and
      less cine DAP (130 +/- 106 cGycm vs 1,399 +/- 1,342 cGycm). Considering all
      procedures, total DAP was reduced by 60% using INRT. CONCLUSION: Novel INRT
      results in a substantial lowering of radiation dose in device implantation, in
      particular, in complex CRT implantation procedures requiring high image quality.

PMID- 29052250
TI  - Semantic Information and the Syntax of Propositional Attitude Verbs.
AB  - Propositional attitude verbs, such as think and want, have long held interest for
      both theoretical linguists and language acquisitionists because their syntactic,
      semantic, and pragmatic properties display complex interactions that have proven
      difficult to fully capture from either perspective. This paper explores the
      granularity with which these verbs' semantic and pragmatic properties are
      recoverable from their syntactic distributions, using three behavioral
      experiments aimed at explicitly quantifying the relationship between these two
      sets of properties. Experiment 1 gathers a measure of 30 propositional attitude
      verbs' syntactic distributions using an acceptability judgment task. Experiments
      2a and 2b gather measures of semantic similarity between those same verbs using a
      generalized semantic discrimination (triad or "odd man out") task and an ordinal
      (Likert) scale task, respectively. Two kinds of analyses are conducted on the
      data from these experiments. The first compares both the acceptability judgments
      and the semantic similarity judgments to previous classifications derived from
      the syntax and semantics literature. The second kind compares the acceptability
      judgments to the semantic similarity judgments directly. Through these
      comparisons, we show that there is quite fine-grained information about
      propositional attitude verbs' semantics carried in their syntactic distributions
      whether one considers the sorts of discrete qualitative classifications that
      linguists traditionally work with or the sorts of continuous quantitative
      classifications that can be derived experimentally.

PMID- 29052251
TI  - Untranslated Parts of Genes Interpreted: Making Heads or Tails of High-Throughput
      Transcriptomic Data via Computational Methods: Computational methods to discover
      and quantify isoforms with alternative untranslated regions.
AB  - In this review we highlight the importance of defining the untranslated parts of
      transcripts, and present a number of computational approaches for the discovery
      and quantification of alternative transcription start and poly-adenylation events
      in high-throughput transcriptomic data. The fate of eukaryotic transcripts is
      closely linked to their untranslated regions, which are determined by the
      position at which transcription starts and ends at a genomic locus. Although the
      extent of alternative transcription starts and alternative poly-adenylation sites
      has been revealed by sequencing methods focused on the ends of transcripts, the
      application of these methods is not yet widely adopted by the community. We
      suggest that computational methods applied to standard high-throughput
      technologies are a useful, albeit less accurate, alternative to the expertise
      demanding 5' and 3' sequencing and they are the only option for analysing legacy
      transcriptomic data. We review these methods here, focusing on technical
      challenges and arguing for the need to include better normalization of the data
      and more appropriate statistical models of the expected variation in the signal.

PMID- 29052252
TI  - The lone gamer: Social exclusion predicts violent video game preferences and
      fuels aggressive inclinations in adolescent players.
AB  - Violent video game playing has been linked to a wide range of negative outcomes,
      especially in adolescents. In the present research, we focused on a potential
      determinant of adolescents' willingness to play violent video games: social
      exclusion. We also tested whether exclusion can predict increased aggressiveness
      following violent video game playing. In two experiments, we predicted that
      exclusion could increase adolescents' preferences for violent video games and
      interact with violent game playing fostering adolescents' aggressive
      inclinations. In Study 1, 121 adolescents (aged 10-18 years) were randomly
      assigned to a manipulation of social exclusion. Then, they evaluated the violent
      content of nine different video games (violent, nonviolent, or prosocial) and
      reported their willingness to play each presented video game. The results showed
      that excluded participants expressed a greater willingness to play violent games
      than nonviolent or prosocial games. No such effect was found for included
      participants. In Study 2, both inclusionary status and video game contents were
      manipulated. After a manipulation of inclusionary status, 113 adolescents (aged
      11-16 years) were randomly assigned to play either a violent or a nonviolent
      video game. Then, they were given an opportunity to express their aggressive
      inclinations toward the excluders. Results showed that excluded participants who
      played a violent game displayed the highest level of aggressive inclinations than
      participants who were assigned to the other experimental conditions. Overall,
      these findings suggest that exclusion increases preferences for violent games and
      that the combination of exclusion and violent game playing fuels aggressive
      inclinations.

PMID- 29052253
TI  - Acute promyelocytic leukemia and chronic lymphocytic leukemia diagnosed
      concurrently.

PMID- 29052255
TI  - Real Objects Can Impede Conditional Reasoning but Augmented Objects Do Not.
AB  - In this study, Knauff and Johnson-Laird's (2002) visual impedance hypothesis
      (i.e., mental representations with irrelevant visual detail can impede reasoning)
      is applied to the domain of external representations and diagrammatic reasoning.
      We show that the use of real objects and augmented real (AR) objects can control
      human interpretation and reasoning about conditionals. As participants made
      inferences (e.g., an invalid one from "if P then Q" to "P"), they also moved
      objects corresponding to premises. Participants who moved real objects made more
      invalid inferences than those who moved AR objects and those who did not
      manipulate objects (there was no significant difference between the last two
      groups). Our results showed that real objects impeded conditional reasoning, but
      AR objects did not. These findings are explained by the fact that real objects
      may over-specify a single state that exists, while AR objects suggest multiple
      possibilities.

PMID- 29052257
TI  - Utility of reproductive life plans in identification of potentially teratogenic
      medication use: A pilot study.
AB  - BACKGROUND: Teratogenic medications increase risks of miscarriage, fetal death,
      and/or birth defects. It is important to identify whether women of childbearing
      potential are taking these medications and to minimize exposure to these agents
      through change in drug therapy before conception and/or use of effective
      contraception to prevent conception. OBJECTIVE: To determine the utility of
      reproductive life plans as tools to identify women using potentially teratogenic
      medications. METHODS: A retrospective review was conducted on reproductive life
      plans completed by women receiving services as part of the Toledo-Lucas County
      Healthy Start program. The medication section of the reproductive life plan was
      reviewed to determine: if it was completed; categories of medications reported
      (prescription, over-the-counter, vitamin/herbal); potentially teratogenic
      medications listed; contraception use and method. RESULTS: Medication lists were
      completed for 437 of the 580 reproductive life plans reviewed (75%). Thirty-five
      women (8%) reported use of a potentially teratogenic medication; most commonly
      reported agents included blood pressure medications and antidepressants. Only 10
      women taking a potentially teratogenic medication (29%) reported using some form
      of contraception, half of which reported use of a less effective method such as
      condoms. CONCLUSION: The reproductive life plan can be a useful tool to identify
      women of childbearing age who require intervention due to use of potentially
      teratogenic medications. Efforts are needed to ensure complete and accurate
      reporting of medication use in reproductive life plans, and to promote effective
      contraceptive use among women taking potentially teratogenic medications.

PMID- 29052258
TI  - Challenges of Rasthryia Swasthya Bima Yojana (RSBY) in West Bengal, India: An
      exploratory study.
AB  - This study reviews the economic viability of the Rashtriya Swasthya Bima Yojana
      (RSBY), India's landmark health insurance program for below poverty line (BPL)
      populations in West Bengal state of India. It addresses the issue through in
      depth analysis of literature, national and state level data, and a number of key
      stakeholder interviews. The study argues that the market failure conditions of
      this insurance model will continue to perpetuate losses for not only the state,
      but also for insurance companies, unless they adjust on a continuous basis for
      profit by raising the premium rate. This will further deplete state budgets for
      health care affecting the viability of the scheme in the long run.

PMID- 29052256
TI  - Structure and Function of Human Tyrosinase and Tyrosinase-Related Proteins.
AB  - Melanin is the main pigment responsible for the color of human skin, hair and
      eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), and
      the tyrosinase-related proteins TYRP1 and TYRP2. The difficulty of isolating pure
      and homogeneous proteins from endogenous sources has hampered their study, and
      resulted in many contradictory findings regarding their physiological functions.
      In this review, we summarize recent advances on the structure and function of TYR
      and TYRPs by virtue of the crystal structure of human TYRP1, which is the first
      available structure of a mammalian melanogenic enzyme. This structure, combined
      with tyrosinase structures from other lower eukaryotes and mutagenesis studies of
      key active site residues, sheds light on the mechanism of TYR and TYRPs.
      Furthermore, a TYRP1-based homology model of TYR provides a high-quality platform
      to map and analyze albinism-related mutations, as well as the design of specific
      antimelanogenic compounds. Finally, we provide perspectives for future
      structure/function studies of TYR and TYRPs.

PMID- 29052259
TI  - Molecular Switches for any pH: A Systematic Study of the Versatile Coordination
      Behaviour of Cyclam Scorpionands.
AB  - Molecular switches have many potential applications in nanoscience and
      biomedicine. Transition metal complexes that can be switched from an inert,
      unreactive state to a catalytically active one by a simple change in conditions
      (e.g. pH shift) or by binding to a specific biomolecular target-so-called target
      activated metal complexes (TAMCs)-hold particular allure as a means of harnessing
      the potent but at times indiscriminate reactivity of metal-based drugs. Towards
      this goal, we have prepared a series of ten structurally related ligands, each of
      which bears a different pendant side-arm functional group appended to a common
      macrocyclic core, along with copper(II) and nickel(II) complexes of these cyclam
      based "molecular scorpionands". X-ray crystal structures reveal a variety of
      binding modes between pendant side-arm and metal centre that depend on the
      constituent donor atoms. To investigate the switchability of side-arm
      coordination in solution, spectrophotometric pH titrations were carried out for
      all 20 metal complexes. The majority of the complexes undergo spectroscopic
      changes that are consistent with a switch in pendant coordination state at a
      specific pH. This ligand series represents a comprehensive model platform from
      which to build pH-switchable metal complexes for applications in nanoscience and
      biomedicine.

PMID- 29052261
TI  - A Facile and Green Method for the Synthesis of SFE Borosilicate Zeolite and Its
      Heteroatom-Substituted Analogues with Promising Catalytic Performances.
AB  - Synthesis of SFE-type borosilcate zeolite was successfully carried out using a
      commercially available low-cost organic structure directing agent (OSDA) with
      ultra-low OSDA and water contents within a short crystallization time. Heteroatom
      (Al, Ti, V, or Fe)-substituted SFE-type zeolite analogues were also directly
      synthesized for the first time. The obtained Al containing zeolites exhibited
      promising catalytic performances in the disproportionation of
      isopropylnaphthalene.

PMID- 29052260
TI  - Increased survival rates in gastric cancer, with a narrowing gender gap and
      widening socioeconomic status gap: A period analysis from 1984 to 2013.
AB  - BACKGROUND AND AIM: Gastric cancer (GC) has the fifth highest incidence rate of
      all cancers and has a poor prognosis. However, no recent large-scale and long
      term studies have evaluated the incidence and survival rates of individuals with
      GC. METHODS: In order to explore the change of GC incidence and survival rates by
      age, gender, race, and socioeconomic status (SES), incidence data and survival
      status of patients with GC between 1984 and 2013 were abstracted from the
      Surveillance, Epidemiology, and End Results database. Totally, 87 242 cases of GC
      were exported and were analyzed. RESULTS: During these three decades, the
      incidence of GC was 7.4, 6.8, and 5.5 per 100 000 individuals in each decade. The
      1-year relative survival rates (RSRs) improved from 42.4% to 44.3% to 49.0% (P <
      0.0001), with a larger increase seen in the third decade. However, the long-term
      survival rates remained low (from 17.8% to 20.3% to 22.9% for the 5-year RSRs, P
      < 0.0001; from 14.1% to 16.4% to 18.6% for the 10-year RSRs, P < 0.0001).
      CONCLUSION: Our analysis demonstrated the decreased incidence and increased
      survival rate of GC. In addition, lower SES was associated with lower survival
      rates. It is notable that others (primarily for Asians) had the highest incidence
      rate but had better outcomes than Whites and Blacks.

PMID- 29052262
TI  - Diversion evaluations: a specialized forensic examination.
AB  - Diversion programs screen justice-involved individuals for the presence of
      psychiatric disorders, and after negotiations take place with attorneys and
      treatment providers, these programs link participants with community-based
      treatment programs in lieu of incarceration. As the number of diversion programs,
      including mental health courts, continues to rapidly grow, so does the need for
      "diversion evaluations". Diversion evaluations are a type of forensic mental
      health assessment (FMHA) conducted to assist the courts in making decisions
      regarding diversion eligibility. As a result, they should follow the general
      principles of FMHA and the American Academy of Psychiatry and Law Practice
      Guideline for Forensic Assessment. Diversion evaluations also require application
      of specific areas of knowledge and experience, as court-based diversion is a
      unique, therapeutically focused context that is purposefully non-adversarial. The
      diversion evaluator is a role that combines objective decision-making with
      clinical consultation. The purpose of this article is to apply generally accepted
      forensic report standards to diversion evaluations, with a particular focus on
      the unique issues of diversion-specific forensic evaluations.

PMID- 29052254
TI  - Genetic polymorphisms associated with smoking behaviour predict the risk of
      surgery in patients with Crohn's disease.
AB  - BACKGROUND: Smoking is a strong environmental factor leading to adverse outcomes
      in Crohn's disease, but a more benign course in ulcerative colitis. Several
      single nucleotide polymorphisms (SNPs) are associated with smoking quantity and
      behaviour. AIM: To assess whether smoking-associated SNPs interact with smoking
      to influence the clinical course of inflammatory bowel diseases. METHODS: Genetic
      and prospectively obtained clinical data from 1434 Swiss inflammatory bowel
      disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were
      analysed. Six SNPs associated with smoking quantity and behaviour (rs588765,
      rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a
      risk score (range: 0-12) by adding the number of risk alleles. We calculated
      multivariate models for smoking, risk of surgery, fistula, Crohn's disease
      location and ulcerative colitis disease extent. RESULTS: In Crohn's disease
      patients who smoke, the number of surgeries was associated with the genetic risk
      score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to
      5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk
      alleles than individuals with the lowest risk. Patients with a risk score >7 had
      a significantly shorter time to first intestinal surgery. The genetic risk score
      did not predict surgery in ulcerative colitis or occurrence of fistulae in
      Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease
      (P<.05) and proctitis in ulcerative colitis (P<.05). CONCLUSIONS: SNPs associated
      with smoking quantity is associated with an increased risk for surgery in Crohn's
      disease patients who smoke. Our data provide an example of genetics interacting
      with the environment to influence the disease course of inflammatory bowel
      disease.

PMID- 29052263
TI  - Angiotensin II-C-C chemokine receptor2/5 axis-dependent monocyte/macrophage
      recruitment contributes to progression of experimental autoimmune myocarditis.
AB  - Angiotensin II (ANG II) plays critical roles in modulation of circulatory
      homeostasis and activation of innate and adaptive immunity and has also been
      implicated in several mouse models of autoimmune disease. However, how ANG II
      regulates macrophages and is involved in development of experimental autoimmune
      myocarditis (EAM) remains unclear. Therefore, the present study aimed to address
      the above question and explore possible mechanisms. EAM was induced in BALB/c
      mice. ANG II was quantitated by ELISA and hematoxylin and eosin staining was
      employed to analyze pathological changes and macrophage infiltration. The
      chemotactic ability of ANG II was assessed by using a Transwell system. It was
      found that ANG II is up-regulated in serum and heart tissues of mice with EAM and
      that ANG II significantly drives monocyte/macrophage infiltration through the C-C
      chemokine receptor 2/5 (CCR2/5) axis. CCR2/5 antagonists and ANG II receptor
      inhibitor could all abrogate monocyte/macrophage infiltration and ameliorate
      development of EAM. Our results have firstly identified a novel function of ANG
      II: that it is a critical chemokine for monocyte/macrophage recruitment.
      Furthermore, our results indicate that ANG II is a potential candidate for
      treatment of inflammatory diseases.

PMID- 29052264
TI  - Photoresponsive Electrodes Modified with DNA Duplexes Possessing a Porphyrin
      Dimer.
AB  - This work describes the formation of a porphyrin (Por) dimer using a DNA duplex
      as a scaffold and photocurrent generation from electrodes modified with a
      monolayer of Por-DNA conjugates. The solid-phase click reaction between an azide
      porphyrin and oligonucleotide labeled with an ethynyl group on CPG support was
      utilized to conjugate the Por to the DNA. UV/Vis absorption and circular
      dichroism (CD) spectral studies revealed that the Por dimer can be formed through
      DNA hybridization and that through-space electronic interactions, characterized
      from the exciton-coupled absorption and the bisignate CD, can occur between the
      two Por molecules. Photoelectrochemical experiments were performed for the
      electrodes functionalized with a monolayer composed of the Por-DNA conjugates. It
      was found that the Por dimer on the electrode, which was designed to resemble the
      special pair in natural photosynthesis, shows efficient photocurrent generation
      in the presence of electron-acceptor reagents compared with the Por monomer.
      These findings strongly support the idea that the DNA structures could be useful
      to construct Por arrays, which is essential for the design of photo- and bio
      electronic devices.

PMID- 29052265
TI  - New mothers' feelings of disappointment and failure after cesarean delivery.
AB  - BACKGROUND: Childbirth is an important life event and how women feel in
      retrospect about their first childbirth may have long-term effects on the mother,
      child, and family. In this study, we investigated the association between mode of
      delivery at first childbirth and birth experience, using a new scale developed
      specifically to measure women's affective response. METHODS: This was a
      prospective cohort study of 3006 women who were interviewed during pregnancy and
      1-month postpartum. The First Baby Study Birth Experience Scale was used to
      measure the association between mode of delivery and women's postpartum feelings
      about their childbirth, taking into account relevant confounders, including
      maternal age, race, education, pregnancy intendedness, depression, social
      support, and maternal and newborn complications by way of linear and logistic
      regression models. RESULTS: Women who had unplanned cesarean delivery had the
      least positive feelings overall about their first childbirth, in comparison to
      those whose deliveries were spontaneous vaginal (P < .001), instrumental vaginal
      (P = .001), and planned cesarean (P < .001). In addition, those who delivered by
      unplanned cesarean were more likely to feel disappointed (adjusted odds ratio
      [OR] 6.21 [95% confidence interval (CI) 4.62-8.35]) and like a failure (adjusted
      OR 5.09 [95% CI 3.65-7.09]) in comparison to women who had spontaneous vaginal
      delivery; and less likely to feel extremely or quite a bit proud of themselves
      (adjusted OR 2.70 [95% CI 2.20-3.30]). CONCLUSIONS: Delivering by unplanned
      cesarean delivery adversely affects how women feel about their first childbirth
      in retrospect, and their self-esteem.

PMID- 29052266
TI  - Detection of the mcr-1 gene in colistin-resistant Escherichia coli from retail
      meat in Japan.
AB  - In this study, the presence of the mcr-1 gene in Escherichia coli from retail
      meat in Japan was investigated. Nine E. coli isolates (eight from chickens and
      one from pork) carried the mcr-1 gene on the plasmid. In six isolates from
      domestic chickens, mcr-1 was located on the IncI2 plasmid, which is approximately
      60 kb in size. In the remaining three isolates from imported chicken and pork,
      mcr-1 was located on the IncX4 plasmid (30 kb).

PMID- 29052267
TI  - T1 mapping with the variable flip angle technique: A simple correction for
      insufficient spoiling of transverse magnetization.
AB  - PURPOSE: The variable flip angle method derives T1 maps from radiofrequency
      spoiled gradient-echo data sets, acquired with different flip angles alpha.
      Because the method assumes validity of the Ernst equation, insufficient spoiling
      of transverse magnetization yields errors in T1 estimation, depending on the
      chosen radiofrequency-spoiling phase increment (Deltaphi). This paper presents a
      versatile correction method that uses modified flip angles alpha' to restore the
      validity of the Ernst equation. METHODS: Spoiled gradient-echo signals were
      simulated for three commonly used phase increments Deltaphi (50 degrees /117
      degrees /150 degrees ), different values of alpha, repetition time (TR), T1 , and
      a T2 of 85 ms. For each parameter combination, alpha' (for which the Ernst
      equation yielded the same signal) and a correction factor CDeltaphi (alpha, TR,
      T1 ) = alpha'/alpha were determined. CDeltaphi was found to be independent of T1
      and fitted as polynomial CDeltaphi (alpha, TR), allowing to calculate alpha' for
      any protocol using this Deltaphi. The accuracy of the correction method for T2
      values deviating from 85 ms was also determined. The method was tested in vitro
      and in vivo for variable flip angle scans with different acquisition parameters.
      RESULTS: The technique considerably improved the accuracy of variable flip angle
      based T1 maps in vitro and in vivo. CONCLUSIONS: The proposed method allows for a
      simple correction of insufficient spoiling in gradient-echo data. The required
      polynomial parameters are supplied for three common Deltaphi. Magn Reson Med
      79:3082-3092, 2018. (c) 2017 International Society for Magnetic Resonance in
      Medicine.

PMID- 29052268
TI  - The Development of Functional Mesocrystals for Energy Harvesting, Storage, and
      Conversion.
AB  - Higher-ordered semiconductors have attracted extensive research interest as an
      adopted engineering for active solar energy harvesting, storage, and conversion.
      It is well-known that the effective separation and anisotropic migration of
      photogenerated charges are the basic driven force required for superior
      efficiency. However, the morphology and stoichiometric variation of these
      semiconductors play essential roles in their physicochemical properties of bulk
      and surface, especially for efficient interparticle or interfacial charge
      transfer. To this point, the strategy of controlling the topotactic
      transformation toward superstructures with optimized functionality is preferable
      for a wide range of optoelectronic and catalytic engineering applications. In
      this Minireview, we provide an overview of the crystal orientation, synthetic
      engineering, functional applications, and spatial and temporal charge dynamics in
      TiO2 mesocrystals and others. The viewpoint of in-depth understanding of the
      structure-related kinetics would offer an opportunity for design of versatile
      mesocrystal semiconductors sought-after for potential applications.

PMID- 29052269
TI  - Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase
      dependent metabolic signal.
AB  - Biotin is an essential cofactor utilized by all domains of life, but only
      synthesized by bacteria, fungi and plants, making biotin biosynthesis a target
      for antimicrobial development. To understand biotin biosynthesis in mycobacteria,
      we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and
      identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The
      biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally
      induce late stage biotin biosynthetic genes in low biotin conditions. Loss of
      bioQ, the repressor of biotin biosynthesis, in the pyc::tn strain reverted biotin
      auxotrophy, as did reconstituting the last step of the pathway through
      heterologous expression of BioB and provision of its substrate DTB. The role of
      Pyc in biotin regulation required its catalytic activities and could be supported
      by M. tuberculosis Pyc. Quantitation of the kinetics of depletion of biotinylated
      proteins after biotin withdrawal revealed that Pyc is the most rapidly depleted
      biotinylated protein and metabolomics revealed a broad metabolic shift in wild
      type cells upon biotin withdrawal which was blunted in cell lacking Pyc. Our data
      indicate that mycobacterial cells monitor biotin sufficiency through a metabolic
      signal generated by dysfunction of a biotinylated protein of central metabolism.

PMID- 29052270
TI  - Crystal structure of the human dual specificity phosphatase 1 catalytic domain.
AB  - The dual specificity phosphatase DUSP1 was the first mitogen activated protein
      kinase phosphatase (MKP) to be identified. It dephosphorylates conserved tyrosine
      and threonine residues in the activation loops of mitogen activated protein
      kinases ERK2, JNK1 and p38-alpha. Here, we report the crystal structure of the
      human DUSP1 catalytic domain at 2.49 A resolution. Uniquely, the protein was
      crystallized as an MBP fusion protein in complex with a monobody that binds to
      MBP. Sulfate ions occupy the phosphotyrosine and putative phosphothreonine
      binding sites in the DUSP1 catalytic domain.

PMID- 29052271
TI  - Living with a resected rectum after rectal cancer surgery-Struggling not to let
      bowel function control life.
AB  - AIMS AND OBJECTIVE: To illuminate what it means to live with a resected rectum
      due to rectal cancer, after reversal of a temporary loop ileostomy. BACKGROUND:
      Today, treatment for rectal cancer is performed with increasing emphasis on
      sphincter-saving surgery, meaning that an anterior resection often includes
      construction of a temporary loop ileostomy that is later reversed. The majority
      of patients will subsequently have disordered bowel function, with symptoms
      ranging from urgency to faecal incontinence. The symptoms are thought to decrease
      over time, reaching a plateau 1 year after surgery. There is a lack of knowledge
      about patients' lived experience after 1 year. DESIGN: An explorative qualitative
      study. METHODS: In-depth interviews were conducted with ten participants, 12-20
      months after surgical closure of a temporary loop ileostomy following rectal
      cancer surgery. The transcribed interviews were analysed using a phenomenological
      hermeneutical method. RESULTS: The thematic structural analysis resulted in three
      themes: living with uncertainty, struggling to live with altered bowel function
      and a preoccupation with bowel function. In the comprehensive understanding, a
      deeper overall understanding emerged, illuminating that the meaning of living
      with a resected rectum could be interpreted as being resilient. CONCLUSIONS: The
      participants' lived experiences were understood as being resilient in that they
      struggled with the uncertainty and adversity of living with an unpredictable
      bowel, which was a constantly preoccupation and affected every aspect of life.
      The participants had not yet adapted to their situation but were struggling in
      solitude to get there, with little or no help from healthcare professionals.
      RELEVANCE TO CLINICAL PRACTICE: The insight from this study highlights the
      importance of patients being systematically examined and followed up in regard to
      functional results and impact of symptoms on everyday life. Treatment,
      information, advice and counselling should be given to promote adaption to the
      new situation.

PMID- 29052272
TI  - Ethical issues in palliative care for nursing homes: Development and testing of a
      survey instrument.
AB  - AIMS AND OBJECTIVES: To develop and psychometrically assess a survey instrument
      identifying ethical issues during palliative care provision in nursing homes.
      BACKGROUND: Registered nurses and healthcare assistants have reported ethical
      issues in everyday palliative care provision. Identifying these issues provides
      evidence to inform practice development to support healthcare workers. DESIGN:
      Cross-sectional survey of Registered nurses and healthcare assistants in nursing
      homes in one region of the UK. METHOD: A survey instrument, "Ethical issues in
      Palliative Care for Nursing homes", was developed through the findings of
      qualitative interviews with Registered nurses and healthcare assistants in
      nursing homes and a literature review. It was reviewed by an expert panel and
      piloted prior to implementation in a survey in 2015 with a convenience sample of
      596 Registered nurses and healthcare assistants. Descriptive and exploratory
      factor analyses were used to assess the underlying structure of the Frequency and
      Distress Scales within the instrument. RESULTS: Analysis of 201 responses
      (response rate = 33.7%) revealed four factors for the Frequency Scale and five
      factors for the Distress Scale that comprise the Ethical issues in Palliative
      Care for Nursing homes. Factors common to both scales included "Processes of
      care," "Resident autonomy" and "Burdensome treatment." Additionally, the
      Frequency Scale included "Competency," and the Distress Scale included "Quality
      of care" and "Communication." CONCLUSION: The Ethical issues in Palliative Care
      for Nursing homes instrument has added to the palliative care knowledge base by
      considering the ethical issues experienced specifically by Registered nurses and
      healthcare assistants within the nursing home. This research offers preliminary
      evidence of the psychometric properties of the Ethical issues in Palliative Care
      for Nursing homes survey instrument. RELEVANCE TO PRACTICE: The two largest
      factors highlight the need to address the organisational aspects of caring and
      provide training in negotiating conflicting ethical principles.

PMID- 29052273
TI  - The relationship of interpersonal sensitivity and depression among patients with
      chronic atrophic gastritis: The mediating role of coping styles.
AB  - AIMS AND OBJECTIVES: To investigate the prevalence of depression and the
      relationship among interpersonal sensitivity, coping styles and depression in
      patients with chronic atrophic gastritis and explore the mediating role of coping
      styles between interpersonal sensitivity and depression. METHODS: A cross
      sectional survey of 101 patients diagnosed with chronic atrophic gastritis aged
      33-83 years. All the participants were surveyed face to face and given the
      informed consent. Sociodemographic and clinical characteristics, the
      interpersonal sensitivity dimension of the Symptoms Checklist-90-Revised, the
      Trait Coping Style Questionnaire and Hospital Depression Scale were measured. A
      descriptive analysis and a correlation matrix were used to illuminate the
      characteristics of subjects and bivariate correlations, respectively.
      Hierarchical regression analysis and bootstrapping method were used to test the
      mediating effect of coping styles between interpersonal sensitivity and
      depression. RESULTS: The prevalence of depression among patients with chronic
      atrophic gastritis was 54.50%. The regression analysis revealed that
      interpersonal sensitivity was positively related to depression. The effect of
      interpersonal sensitivity on depression was partially mediated by coping styles,
      including positive coping and negative coping. CONCLUSIONS: Depression was highly
      prevalent in patients with chronic atrophic gastritis. Coping styles played a
      mediating role between interpersonal sensitivity and depression, which had
      important clinical implications for physicians and nurses. RELEVANCE TO CLINICAL
      PRACTICE: Patients who are at high risk of depression should be identified and
      applicable targets should be made for prevention and intervention, in
      consideration of mental health of patients with chronic atrophic gastritis.

PMID- 29052274
TI  - Health education and competency scale: Development and testing.
AB  - AIMS AND OBJECTIVE: To develop a tool for measuring competency in conducting
      health education and to evaluate its psychometric properties in a population of
      entry-level nurses. BACKGROUND: Until now, no generic instrument has been
      developed specifically for measuring competency in health education, which is an
      essential competency for nurses. Existing scales are either insufficient for
      psychometric evaluation or are designed specifically for senior nurses. To
      evaluate curricula and courses designed for entry-level nurses, educators require
      an instrument for measuring improvement in core competency from baseline to
      determine whether the minimum level of ability has been achieved. DESIGN: Item
      development for the survey instrument used for data collection in this study was
      based on the results of a literature review. METHODS: The self-evaluated Health
      Education Competency Scale developed in this study was used to survey 457 nursing
      students at two nursing schools and 165 clinical nurses at a medical centre in
      south Taiwan in 2016. The participants were randomly divided into two equal
      groups. One group was analysed by exploratory factor analysis with varimax
      rotation, and one group was analysed by confirmatory factor analysis. RESULTS:
      Factor analysis yielded a four-factor (assessment, pedagogy, motivation and
      empowerment) solution (18 items) that accounted for 75.9% of the variance.
      CONCLUSION: The total scale and subscales had good reliabilities and construct
      validity coefficients. For measuring competency in entry-level nurses, the Health
      Education Competency Scale had a good data fit and sound psychometric properties.
      RELEVANCE TO CLINICAL PRACTICE: The proposed scale can be used to assess health
      education competency for college nursing students and practising nurses.
      Furthermore, it can provide educators with valuable insight into the minimum
      competencies required for entry-level nurses to deliver quality health care to
      clients and can guide them in the practice of client-based teaching.

PMID- 29052275
TI  - Effectiveness of current policing-related mental health interventions: A
      systematic review.
AB  - BACKGROUND: There are three commonly used mental health interventions associated
      with policing: liaison and diversion, street triage and having specialist staff
      embedded in police contact control rooms. Crisis intervention teams (CITs),
      already used in the USA, are now attracting wider interest, including in the UK.
      Investment in these interventions is growing, so it is important to have evidence
      of their effectiveness. AIM: To conduct a systematic literature review to answer
      questions about effectiveness of police-mental health service models for
      responding to people with mental disorder and suspected offending or public
      safety problems. METHODS: A population/participant, intervention/indicator,
      comparator/control, outcome (PICO) framework was developed and keywords used to
      locate research studies within 29 databases. The 3179 results returned were
      screened by two researchers against preset inclusion and exclusion criteria. This
      resulted in 23 studies being included from which were taken the study methodology
      and findings and on which a narrative synthesis was conducted. RESULTS: Twenty
      three studies could be included, overall showing a positive impact of the
      interventions considered, but no well-designed randomised controlled trials to
      test this optimistic view rigorously. CONCLUSIONS: Overall, rather than
      indicating that one approach is more effective than another, the review points to
      the need for a multi-faceted approach within a structured and integrated model,
      such as the CIT model. This is generally not the current pattern of
      interventions, and policy makers, service commissioners and providers may wish to
      review future options. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29052276
TI  - Association of spiritual/religious coping with depressive symptoms in high- and
      low-risk pregnant women.
AB  - AIMS AND OBJECTIVES: To investigate the role of spiritual/religious coping (SRC)
      on depressive symptoms in high- and low-risk pregnant women. BACKGROUND:
      Spiritual/religious coping is associated with physical and mental health
      outcomes. However, only few studies investigated the role of these strategies
      during pregnancy and whether low- and high-risk pregnant women have different
      coping mechanisms. DESIGN: This study is a cross-sectional comparative study.
      METHODS: This study included a total of 160 pregnant women, 80 with low-risk
      pregnancy and 80 with high-risk pregnancy. The Beck Depression Inventory, the
      brief SRC scale and a structured questionnaire on sociodemographic and obstetric
      aspects were used. General linear model regression analysis was used to identify
      the factors associated with positive and negative SRC strategies in both groups
      of pregnant women. RESULTS: Positive SRC use was high, whereas negative SRC use
      was low in both groups. Although we found no difference in SRC strategies between
      the two groups, negative SRC was associated with depression in women with high
      risk pregnancy, but not in those with low-risk pregnancy. Furthermore, positive
      SRC was not associated with depressive symptoms in both groups. CONCLUSIONS:
      Results showed that only the negative SRC strategies of Brazilian women with high
      risk pregnancies were associated with worsened mental health outcomes. RELEVANCE
      TO CLINICAL PRACTICE: Healthcare professionals, obstetricians and nurse midwives
      should focus on the use of negative SRC strategies in their pregnant patients.

PMID- 29052278
TI  - Carnosine and N-acetyl cysteine protect against sodium nitrite-induced oxidative
      stress in rat blood.
AB  - Sodium nitrite (NaNO2 ) is widely used in the food industry as a preservative and
      colorant in meat and fish products. Industrialization and improper agricultural
      practices have greatly increased human exposure to high nitrite levels, mainly
      through contaminated drinking water, causing various health disorders. We have
      investigated the protective effect of carnosine (CAR) and N-acetyl cysteine (NAC)
      on NaNO2 -induced toxicity in rat blood. CAR is a bioactive dipeptide found in
      mammalian muscle while NAC is a synthetic sulfhydryl amino acid and an important
      precursor of glutathione. Animals were given a single acute oral dose of NaNO2 at
      60 mg/kg body weight with or without prior administration of either CAR or NAC.
      Rats were sacrificed after 24 h, blood was withdrawn and plasma and erythrocytes
      were isolated. Administration of NaNO2 alone increased methemoglobin levels and
      methemoglobin reductase activity, decreased the activities of antioxidant defense
      and metabolic enzymes and significantly weakened the total antioxidant capacity
      of rat erythrocytes. Similar effects were seen in plasma of NaNO2 -treated rats.
      In contrast, administration of CAR or NAC, prior to NaNO2 treatment, markedly
      attenuated the NaNO2 -elicited deleterious effects. Thus, CAR and NAC can
      mitigate nitrite-induced metabolic alterations and oxidative damage probably due
      to their intrinsic biochemical antioxidant properties. This study suggests that
      CAR and NAC can be potentially used as therapeutic/protective agents against
      NaNO2 toxicity.

PMID- 29052277
TI  - Src promotes EGF-induced epithelial-to-mesenchymal transition and migration in
      gastric cancer cells by upregulating ZEB1 and ZEB2 through AKT.
AB  - Epithelial-to-mesenchymal transition (EMT) plays important roles in the
      migration, invasion, and metastasis of cancer cells. However, the role of Src in
      epidermal growth factor (EGF)-induced EMT and migration in gastric cancer cells
      remains to be clarified. In the current study, the effect of Src on EGF
      stimulated EMT and migration was explored in gastric cancer cells. EGF induced
      EMT in gastric cancer cells and increased their migratory ability, which was
      accompanied by the phosphorylation of Src. PP2, the Src inhibitor, markedly
      suppressed EGF-mediated EMT and migration in gastric cancer cells. Additionally,
      EGF-stimulated upregulation of zinc finger E-box binding homeobox 1 (ZEB1) and
      zinc finger E-box binding homeobox 2 (ZEB2) was significantly repressed by PP2.
      Further analysis showed that EGF-stimulated phosphorylation of protein kinase B
      (AKT) was almost completely abolished by PP2, whereas that of extracellular
      signal-regulated kinase (ERK), signal transducer and activator of transcription 3
      (STAT3) was only mildly suppressed. Moreover, LY294002, the AKT inhibitor,
      significantly inhibited EGF-induced upregulation of ZEB1 and ZEB2 as well as EMT
      and migration stimulated by EGF in gastric cancer cells. However, neither ERK
      inhibitor nor STAT3 inhibitor repressed EGF-induced EMT-related changes. Taken
      together, these results suggest that Src promotes EGF-stimulated EMT and
      migration by upregulation of ZEB1 and ZEB2 through AKT signaling pathway in
      gastric cancer cells.

PMID- 29052279
TI  - Combining protein sequence, structure, and dynamics: A novel approach for
      functional evolution analysis of PAS domain superfamily.
AB  - PAS domains are widespread in archaea, bacteria, and eukaryota, and play
      important roles in various functions. In this study, we aim to explore functional
      evolutionary relationship among proteins in the PAS domain superfamily in view of
      the sequence-structure-dynamics-function relationship. We collected protein
      sequences and crystal structure data from RCSB Protein Data Bank of the PAS
      domain superfamily belonging to three biological functions (nucleotide binding,
      photoreceptor activity, and transferase activity). Protein sequences were aligned
      and then used to select sequence-conserved residues and build phylogenetic tree.
      Three-dimensional structure alignment was also applied to obtain structure
      conserved residues. The protein dynamics were analyzed using elastic network
      model (ENM) and validated by molecular dynamics (MD) simulation. The result
      showed that the proteins with same function could be grouped by sequence
      similarity, and proteins in different functional groups displayed statistically
      significant difference in their vibrational patterns. Interestingly, in all three
      functional groups, conserved amino acid residues identified by sequence and
      structure conservation analysis generally have a lower fluctuation than other
      residues. In addition, the fluctuation of conserved residues in each biological
      function group was strongly correlated with the corresponding biological
      function. This research suggested a direct connection in which the protein
      sequences were related to various functions through structural dynamics. This is
      a new attempt to delineate functional evolution of proteins using the integrated
      information of sequence, structure, and dynamics.

PMID- 29052280
TI  - Reappraisal of systemic venous chemoreceptors: might they explain the matching of
      breathing to metabolic rate in humans?
AB  - NEW FINDINGS: What is the topic of this review? One of the major unanswered
      questions in physiology is that of how breathing matches metabolic rate. Venous
      chemoreceptors seem to have been dismissed since the 1960s. What advances does it
      highlight? New evidence shows that their apparent dismissal needs reappraisal.
      The paper on which this depends has more than one interpretation, and another
      paper obtained the opposite result. Previous search ignored all locations between
      skeletal muscle and the right heart. Oxygen sensors other than the arterial
      chemoreceptors do exist. Heymans and colleagues originally demonstrated some
      residual breathing response to hypoxia in sino-aortically denervated animals.
      Similar results occur in humans. One of the major unanswered questions in
      physiology is that of how breathing matches metabolic rate. The existence in
      humans of venous chemoreceptors that might control breathing seems to have been
      dismissed since the 1960s. New evidence has emerged showing that this apparent
      dismissal needs reappraisal. First, the paper in humans on which this depends has
      more than one interpretation. Moreover, a previous paper obtained the opposite
      result and is not cited. Secondly, previous search for venous chemoreceptors
      failed to examine all venous locations between skeletal muscle and the right
      heart and lungs. Thirdly, oxygen sensors other than the arterial chemoreceptors
      do exist. Heymans himself originally demonstrated some residual breathing
      response to hypoxia in sino-aortically denervated animals. Others confirm a
      residual breathing response to hypoxia in mammals, including humans. There is now
      considerable interest in the importance of afferent feedback in controlling the
      cardiovascular and respiratory systems. Moreover, it is now clear that arterial,
      aortic and central chemoreceptors have no role in explaining how breathing
      matches metabolic rate during exercise. These together provide a timely reminder
      that venous chemoreceptors remain ideal candidates still to be considered as
      metabolic rate sensors to explain matching in humans. Firstly, this is because
      venous PO2 and PCO2 values do change appropriately in proportion to metabolic
      rate, so a metabolic rate signal sufficient to drive breathing might already
      exist. Secondly, chemoreceptor-like anatomical structures are present in the
      systemic venous system but remain unexplored. Finally, no extant experimental
      evidence precludes their existence.

PMID- 29052281
TI  - Jansen-MIDAS: A multi-level photomicrograph segmentation software based on
      isotropic undecimated wavelets.
AB  - Image segmentation, the process of separating the elements within a picture, is
      frequently used for obtaining information from photomicrographs. Segmentation
      methods should be used with reservations, since incorrect results can mislead
      when interpreting regions of interest (ROI). This decreases the success rate of
      extra procedures. Multi-Level Starlet Segmentation (MLSS) and Multi-Level Starlet
      Optimal Segmentation (MLSOS) were developed to be an alternative for general
      segmentation tools. These methods gave rise to Jansen-MIDAS, an open-source
      software. A scientist can use it to obtain several segmentations of hers/his
      photomicrographs. It is a reliable alternative to process different types of
      photomicrographs: previous versions of Jansen-MIDAS were used to segment ROI in
      photomicrographs of two different materials, with an accuracy superior to 89%.

PMID- 29052282
TI  - Nursing staff intentions towards managing deteriorating health in nursing homes:
      A convergent parallel mixed-methods study using the theory of planned behaviour.
AB  - AIMS AND OBJECTIVES: To predict the factors that are most important in explaining
      nursing staff intentions towards early detection of the deteriorating health of a
      resident and providing subacute care in the nursing home setting. BACKGROUND:
      Nursing staff play a pivotal role in managing the deteriorating resident and
      determining whether the resident needs to be transferred to hospital or remain in
      the nursing home; however, there is a dearth of literature that explains the
      factors that influence their intentions. This information is needed to underpin
      hospital avoidance programs that aim to enhance nursing confidence and skills in
      this area. DESIGN: A convergent parallel mixed-methods study, using the theory of
      planned behaviour as a framework. METHODS: Surveys and focus groups were
      conducted with nursing staff (n = 75) at a 94-bed nursing home at two points in
      time, prior to and following the implementation of a hospital avoidance program.
      The quantitative and qualitative data were analysed separately and merged during
      final analysis. RESULTS: Nursing staff had strong intentions, a positive attitude
      that became significantly more positive with the hospital avoidance program in
      place, and a reasonable sense of control; however, the influence of important
      referents was the strongest predictor of intention towards managing residents
      with deteriorating health. Support from a hospital avoidance program empowered
      staff and increased confidence to intervene. CONCLUSION: The theory of planned
      behaviour served as an effective framework for identifying the strong influence
      referents had on nursing staff intentions around managing residents with
      deteriorating health. Although nursing staff had a reasonable sense of control
      over this area of their work, they believed they benefitted from a hospital
      avoidance program initiated by the nursing home. RELEVANCE TO CLINICAL PRACTICE:
      Managers implementing hospital avoidance programs should consider the role of
      referents, appraise the known barriers and facilitators and take steps to
      identify those unique to their local situation. All levels of nursing staff play
      a role in preventing hospitalisation and should be consulted in the design,
      implementation and evaluation of any hospital avoidance strategies.

PMID- 29052283
TI  - Characteristics of alleged homicide offenders with and without schizophrenia in
      Sichuan, China.
AB  - BACKGROUND: Little is known about the characteristics of people with and without
      schizophrenia who have been charged with homicide in China. AIMS AND RESEARCH
      QUESTION: Our research question was what differences are there between alleged
      homicide offenders with and without psychosis? METHOD: All archival records of
      alleged homicide cases referred for assessment to the West China Forensic Central
      Medical Service during 1998-2006 were retrieved. The centre serves a large
      catchment area in the mainly rural province of Sichuan. A random 20% of cases
      with schizophrenia and all cases without psychosis were selected for comparison.
      Demographic, criminological and mental health data were extracted from the
      records, and violence was rated by using the Violence Risk Scale (Chinese
      version). RESULTS: The two groups differed significantly in age, education,
      occupation, marital status and relationships to victim. The estimated risk of
      reoffending was higher in the schizophrenia group than the non-psychotic group,
      even after controlling for demographic differences. Despite many individuals
      reporting long histories of mental illness, about 40% of those with schizophrenia
      had never had any psychiatric treatment and less than 4% were in treatment at the
      time of the alleged homicide. CONCLUSIONS: The tendency for homicidal people with
      schizophrenia to be older, less educated and more socially isolated than their
      non-psychotic peers is similar to experience in Western countries, but the
      apparently higher risk scale scores of the Chinese schizophrenia group and their
      greater tendency to attack strangers are different. The lack of reported previous
      engagement with mental health services by a clearly ill and risky group of people
      is a likely explanation. Similar rural problems compared with better served urban
      areas have been reported in the Chuvash Republic. The case for better rural
      mental health services seems strong. Copyright (c) 2017 John Wiley & Sons, Ltd.

PMID- 29052284
TI  - Cytological diagnosis of a rare case of primary Merkel cell carcinoma of the
      parotid gland.

PMID- 29052285
TI  - Fitness-related differences in the rate of whole-body evaporative heat loss in
      exercising men are heat-load dependent.
AB  - NEW FINDINGS: What is the central question of this study? Aerobic fitness
      modulates heat loss, but the heat-load threshold at which fitness-related
      differences in heat loss occur in young healthy men remains unclear. What is the
      main finding and its importance? We demonstrate using direct calorimetry that
      aerobic fitness modulates heat loss in a heat-load-dependent manner, with fitness
      related differences occurring between young men who have low and high fitness
      when the heat load is ~>=500 W. Although aerobic fitness has been known for some
      time to modulate heat loss, our findings define the precise heat-load threshold
      at which fitness-related differences occur. The effect of aerobic fitness
      (defined as rate of peak oxygen consumption) on heat loss during exercise is
      thought to be related to the level of heat stress. However, it remains unclear at
      what combined exercise and environmental (net) heat-load threshold these fitness
      related differences occur. To identify this, we assessed whole-body heat exchange
      (dry and evaporative) by direct calorimetry in young (22 +/- 3 years) men matched
      for physical characteristics with low (Low-fit; 39.8 +/- 2.5 ml O2  kg-1  min-1
      ), moderate (Mod-fit; 50.9 +/- 1.2 ml O2  kg-1  min-1 ) and high aerobic fitness
      (High-fit; 62.0 +/- 4.4 ml O2  kg-1  min-1 ; each n = 8), during three 30 min
      bouts of cycling in dry heat (40 degrees C, 12% relative humidity) at increasing
      rates of metabolic heat production of 300 (Ex1), 400 (Ex2) and 500 W (Ex3), each
      followed by a 15 min recovery period. Each group was exposed to a similar net
      heat load (metabolic plus ~100 W dry heat gain; P = 0.83) during each exercise
      bout [~400 (Ex1), ~500 (Ex2) and ~600 W (Ex3); P < 0.01]. Although evaporative
      heat loss was similar between groups during Ex1 (P = 0.33), evaporative heat loss
      was greater in the High-fit (Ex2, 466 +/- 21 W; Ex3, 557 +/- 26 W) compared with
      the Low-fit group (Ex2, 439 +/- 22 W; Ex3, 511 +/- 20 W) during Ex2 and Ex3 (P <=
      0.03). Conversely, evaporative heat loss for the Mod-fit group did not differ
      from either the High-fit or Low-fit group during all exercise bouts (P >= 0.09).
      We demonstrate that aerobic fitness modulates heat loss in a heat-load-dependent
      manner, such that young, highly fit men display greater heat-loss capacity only
      at heat loads ~>=500 W compared with their lesser trained counterparts.

PMID- 29052286
TI  - High-risk respiratory patients' experiences of bronchoscopy with conscious
      sedation and analgesia: A qualitative study.
AB  - AIMS AND OBJECTIVES: To understand the experiences of high-risk respiratory
      patients undergoing bronchoscopy with conscious sedation. BACKGROUND: Due to
      possible complications, high-risk respiratory patients are usually given smaller,
      cautious doses of sedation and analgesia for bronchoscopy. Described as
      "conscious sedation," this facilitates depression of the patient's consciousness
      without causing respiratory compromise. Previously, studies have investigated
      patient experience using quantitative methods. This is the first study that has
      explored the patient experience during bronchoscopy from a qualitative
      perspective. DESIGN: Qualitative, phenomenological approach as described by Van
      Manen. METHODS: The setting was an endoscopy unit within an Australian tertiary
      hospital. Unstructured interviews were conducted with 13 patients with chronic
      obstructive pulmonary disease who underwent day-case bronchoscopy. All
      participants received conscious sedation. They were interviewed twice, within a
      week, postprocedure. Interviews were transcribed verbatim and analysed using Van
      Manen's interpretive approach. FINDINGS: Participants had varying experiences.
      Five themes emerged from the analysis: Frustration and fear; Comfort and safety;
      Choking and coughing; Being aware; and Consequences. Whilst not all participants
      experienced procedural awareness or remembered it, for those who did it was a
      significant event. Overall, experiences were found to be negative; however,
      participants accepted and tolerated them, perceiving them as necessary to obtain
      a diagnostic result. CONCLUSION: The findings demonstrate that often patients are
      aware during the procedure and their experience may be uncomfortable and
      distressing. RELEVANCE TO CLINICAL PRACTICE: These findings have implications for
      patient preparation pre- and post-bronchoscopy in terms of what they might
      expect, and to discuss what has happened after the procedure. Some practices of
      the bronchoscopy team during the procedure may need modification. For example, in
      anticipation of the possibility that the patient may be aware, healthcare
      professionals should provide patient-focused explanations of what is happening
      during the procedure, as well as providing ongoing reassurance that everything is
      going as planned.

PMID- 29052287
TI  - "I'm not sure I'm a nurse": A hermeneutic phenomenological study of nursing home
      nurses' work identity.
AB  - AIMS AND OBJECTIVES: To explore nursing home nurses' experiences and views of
      work identity. BACKGROUND: Nursing home nurses are in a unique position as they
      work at the interface of health and social care. Little is known about nursing
      home nurses' perceptions and experiences of working within this context. Evidence
      suggests that using the concept of work identity can support understanding of how
      workers make sense of their work. DESIGN: Hermeneutic phenomenological study.
      METHODS: The study was carried out in seven nursing homes in North East England.
      Findings are based upon literary analysis of multiple episodic interviews with 13
      nursing home nurses. RESULTS: Participants' responses suggested that nursing
      "residents" is different to nursing "patients," and nursing home nurses are
      required to modify their care activities to account for these differences.
      Participants also proposed that they are isolated and excluded from the rest of
      the healthcare workforce group. These issues led participants to feel uncertain
      about work identity. Many participants attempted to strengthen their work
      identity by aligning their role with what they perceived the "nurse identity" to
      be. CONCLUSION: Nurses' work activities and professional group identity influence
      their work identity. When work activities and professional group identity do not
      align with role expectations, as can be the case for nursing home nurses, work
      identity may be compromised. These nurses may attempt to change work practices to
      strengthen their work identity. RELEVANCE TO CLINICAL PRACTICE: Health- and
      social care providers need to account for work identity factors in the
      organisation of care, and planning and implementation of integrated health- and
      social care initiatives.

PMID- 29052288
TI  - Implementation of a gerontology nurse specialist role in primary health care:
      Health professional and older adult perspectives.
AB  - AIMS AND OBJECTIVES: To explore an innovative primary healthcare gerontology
      nurse specialist role from the perspectives of older people and health
      professionals. BACKGROUND: Primary care is struggling to meet the needs and
      demands of complex older people. New models which incorporate holistic assessment
      and care coordination are necessary. DESIGN: A qualitative descriptive general
      inductive design was used. METHODS: Older people at risk of health and functional
      decline were identified and received a comprehensive gerontology assessment and
      care coordination. Older adults (75 years+) enrolled within one of three primary
      healthcare practices in Auckland, New Zealand were eligible. Healthcare
      professionals directly involved with the primary healthcare gerontology nurse
      specialist model were invited for study participation. Face-to-face interviews
      were held with five older people and six health professionals were interviewed by
      telephone. A semistructured interview guide was used for all interviews. A
      general inductive approach was undertaken for analysis to systematically identify
      codes and themes. RESULTS: Data analysis revealed two central themes from the
      older people perspective: "holistic expertise" and "communication." Two main
      themes were identified from the health professional perspective: "competency" and
      "service delivery." Results showed the gerontology nurse specialist role was
      highly regarded by both older people and the health professionals. The in-home
      comprehensive geriatric assessment was identified as greatly beneficial.
      CONCLUSIONS: The competence and care coordination of the gerontology nurse
      specialist reduced fragmentation and were deemed immensely valuable. Care
      coordination should be recognised as a key component to meeting the complex needs
      of at-risk older people in the community. RELEVANCE TO CLINICAL PRACTICE: The
      expert knowledge of the gerontology nurse specialist and in-home comprehensive
      geriatric assessment were crucial aspects of the new model. Equally important was
      the assimilation of primary and secondary care infrastructure to upskill and
      deliver mentorship to the gerontology nurse specialist.

PMID- 29052289
TI  - Exploring implementation of the Careful Nursing Philosophy and Professional
      Practice Model(c) in hospital-based practice.
AB  - AIM: To explore the effectiveness and feasibility of implementing the two
      clinical dimensions of the Careful Nursing Philosophy and Professional Practice
      Model(c) (Careful Nursing) in an acute care hospital. BACKGROUND: Implementation
      of a professional practice model by nurses in hospitals supports nurses' control
      over their practice and enhances the quality of their contribution to patient
      care. Implementing such change is complex and initially best approached on a
      small scale. METHODS: A mixed methods exploratory design was used. Data were
      sought from 23 professional nurses practising in a 26-bed acute medical ward for
      older persons. Quantitative data were collected on nurses' control over and
      documentation of their practice. Qualitative data were collected on nurses'
      perceptions of their practice. RESULT: Nurses' control over practice and
      adherence to practice documentation standards increased. Overall, the nurses
      perceived Careful Nursing-guided practice positively. Feasibility issues were
      identified and addressed. CONCLUSION: Exploratory evidence suggests that Careful
      Nursing could influence nurses' practice and overall perception of practice
      positively; its implementation is feasible. IMPLICATIONS FOR NURSING MANAGEMENT:
      Careful Nursing offers a distinctive nursing framework for professional practice.
      This study can provide a strategy for implementing Careful Nursing-guided changes
      in hospital-based practice on an exploratory level.

PMID- 29052290
TI  - Pulmonary Langerhans cell histiocytosis "de novo" after lung transplantation.
AB  - A pulmonary Langerhans cell histiocytosis is presented in a 40 year-old woman two
      years after bilateral lung transplantation for emphysema without any signs of
      Langerhans cells proliferation in the explanted lungs. A microsatellite molecular
      analysis showed the proliferating cells were generated in a recipient cellular
      clone. The patient did not quit smoking after transplantation. No signs of
      disease were detected in the implanted lungs before surgery. Strict control of
      immunosupressive drug levels stabilized the disease. A "de novo" monoclonal
      origin of stem cells, probably from the bone marrow is suggested. The reason she
      did not develop disease in the native lungs is unknown, although we suggest an
      interaction between tobacco or some other antigens and local cellular receptors.

PMID- 29052292
TI  - Intravenous ferric carboxymaltose for heart failure with iron deficiency.

PMID- 29052291
TI  - Development of an isotopic stream index connecting physiographic characteristics
      of montane catchments.
AB  - This study is to develop an isotopic catchment-effect index (CEI) connecting the
      physiographic characteristics of stream catchments. A CEI, describing the extent
      of difference in stable water isotopic compositions (delta values) between stream
      water and local precipitation at any given sampling site, can help in judging
      whether water resource management should be focused on upstream regions of
      streams or local hydrology issues. To establish the isotopic CEI, this study
      measured delta values of stream water and derived delta18 O of local
      precipitation based on regional isotopic altitude gradient at montane catchments
      of various sizes. Results indicate that the CEI is strongly related to catchment
      physiographic characteristics, such as length of main stream, mean area, mean
      elevation, perimeter, and slope. These characteristics are considered important
      indices of streamflow. Based on mathematical regression modeling describing the
      relationships between CEI and respective physiographic factors, CEI values can
      predict respective physiographic factors and vice versa. Moreover, according to
      the multiple equations derived in this study, catchments of larger size and
      steeper slope give elevated CEI values while greater stream length reduces the
      CEI's value. A greater CEI value indicates that local stream water is principally
      sourced from upstream reaches rather than contributions from local precipitation.
      In addition, CEI values are greater in winter than in summer resulting from
      monsoon effect. Consequently, this study establishes CEI as a useful descriptor
      of the physiographic characteristics of catchments.

PMID- 29052293
TI  - Butyrate promotes visceral hypersensitivity in an IBS-like model via enteric
      glial cell-derived nerve growth factor.
AB  - BACKGROUND: Altered visceral sensation is common in irritable bowel syndrome
      (IBS) and nerve growth factor (NGF) participates in visceral pain development.
      Sodium butyrate (NaB) could induce colonic hypersensitivity via peripheral up
      regulation of NGF in animals. Enteric glial cells (EGCs) appear to be an
      important source of NGF. Whether butyrate could induce visceral hypersensitivity
      via increased EGC-derived NGF is still unknown. METHODS: CRL-2690 cells were used
      for transcriptome analyses after butyrate treatment. Rats received butyrate
      enemas to induce colonic hypersensitivity. Colorectal distention test was
      performed to assess visceral sensitivity. Immunofluorescence studies were used to
      evaluate the co-expression of glial fibrillary acidic protein (GFAP) and NGF or
      growth associated protein 43 in animal model. NGF expression in rat colon was
      also investigated. In vitro, CRL-2690 cells were stimulated with NaB or
      trichostatin A (TSA). NGF or GFAP expression was also examined. KEY RESULTS:
      Transcriptome analyses showed that butyrate induced marked changes of genes
      expression related to neurotrophic signaling pathways. NaB-treated rats showed
      increased visceral sensitivity. An improved NGF expression level was observed in
      NaB-treated rats. Meanwhile, a 2.1-fold increase in co-expression of GFAP and NGF
      was also determined in rats received NaB enemas. In cultured cells, both NaB and
      TSA treatment could cause obvious NGF expression. Thus, butyrate might regulate
      EGC function via histone deacetylase inhibition. CONCLUSIONS & INFERENCES:
      Butyrate-EGC interplay may play a pivotal role in regulation of NGF expression
      and the development of colonic hypersensitivity in IBS-like animal model.

PMID- 29052294
TI  - Why is the use of digitalis withering? Another reason that we need medical heart
      failure specialists.

PMID- 29052295
TI  - Tropical forests are thermally buffered despite intensive selective logging.
AB  - Tropical rainforests are subject to extensive degradation by commercial selective
      logging. Despite pervasive changes to forest structure, selectively logged
      forests represent vital refugia for global biodiversity. The ability of these
      forests to buffer temperature-sensitive species from climate warming will be an
      important determinant of their future conservation value, although this topic
      remains largely unexplored. Thermal buffering potential is broadly determined by:
      (i) the difference between the "macroclimate" (climate at a local scale, m to ha)
      and the "microclimate" (climate at a fine-scale, mm to m, that is distinct from
      the macroclimate); (ii) thermal stability of microclimates (e.g. variation in
      daily temperatures); and (iii) the availability of microclimates to organisms. We
      compared these metrics in undisturbed primary forest and intensively logged
      forest on Borneo, using thermal images to capture cool microclimates on the
      surface of the forest floor, and information from dataloggers placed inside
      deadwood, tree holes and leaf litter. Although major differences in forest
      structure remained 9-12 years after repeated selective logging, we found that
      logging activity had very little effect on thermal buffering, in terms of
      macroclimate and microclimate temperatures, and the overall availability of
      microclimates. For 1 degrees C warming in the macroclimate, temperature inside
      deadwood, tree holes and leaf litter warmed slightly more in primary forest than
      in logged forest, but the effect amounted to <0.1 degrees C difference between
      forest types. We therefore conclude that selectively logged forests are similar
      to primary forests in their potential for thermal buffering, and subsequent
      ability to retain temperature-sensitive species under climate change. Selectively
      logged forests can play a crucial role in the long-term maintenance of global
      biodiversity.

PMID- 29052296
TI  - microRNA-132: a new biomarker of heart failure at last?

PMID- 29052297
TI  - Recognizing Through-Bond and Through-Space Self-Exchange Charge/Spin Transfer
      Pathways in Bis(triarylamine) Radical Cations with Similar Geometrical
      Arrangements.
AB  - Radical cations of bis(triarylamine)s, 3 and 4, in which the triarylamine redox
      centers are bridged by an ortho-phenylene and ortho-carborane cluster,
      respectively, have been prepared to elucidate the difference in intramolecular
      charge/spin-transfer (ICT/IST) pathway owing to the two different bridging units
      affording similar geometrical arrangements between the redox centers.
      Electrochemistry, absorption spectroscopy, VT-ESR spectroscopy, and DFT
      calculations reveal that 3.+ and 4.+ are classified into class II and class I
      mixed-valence systems, respectively, and therefore, through-bond and through
      space mechanisms are dominant for the ICT/IST phenomena in 3.+ and 4.+ ,
      respectively. Moreover, SQUID measurements for dicationic species provide the
      fact that virtually no spin-exchange interaction is observed for spins in 42+ ,
      while the antiferromagnetic interaction for spins in 32+ , in accordance with the
      existence of a conjugation pathway for the ortho-phenylene bridge.

PMID- 29052299
TI  - A functional variant in the promoter region regulates the C-reactive protein gene
      and is a potential candidate for increased risk of atrial fibrillation.

PMID- 29052298
TI  - Idiopathic gastroparesis is associated with specific transcriptional changes in
      the gastric muscularis externa.
AB  - BACKGROUND: The molecular changes that occur in the stomach that are associated
      with idiopathic gastroparesis are poorly described. The aim of this study was to
      use quantitative analysis of mRNA expression to identify changes in mRNAs
      encoding proteins required for the normal motility functions of the stomach.
      METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic
      control subjects who exhibited no symptoms of gastroparesis and from patients
      with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and
      mRNA expression levels were determined by quantitative reverse transcriptase (RT)
      PCR. KEY RESULTS: Smooth muscle tissue from idiopathic gastroparesis patients had
      decreased expression of mRNAs encoding several contractile proteins, such as
      MYH11 and MYLK1. Conversely, there was no significant change in mRNAs
      characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There
      was also a significant decrease in mRNA-encoding platelet-derived growth factor
      receptor alpha (PDGFRalpha) and its ligand PDGFB and in Heme oxygenase 1 in
      idiopathic gastroparesis subjects. In contrast, there was a small increase in
      mRNA characteristic of neurons. Although there was not an overall change in KIT
      expression in gastroparesis patients, KIT expression showed a significant
      correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRalpha
      showed weak correlations to the fullness/satiety subscore of patient assessment
      of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND
      INFERENCES: Our findings suggest that idiopathic gastroparesis is associated with
      altered smooth muscle cell contractile protein expression and loss of PDGFRalpha+
      cells without a significant change in ICCs.

PMID- 29052300
TI  - Introduction to the symposium 'Targeted therapy in B-cell malignancies'.

PMID- 29052301
TI  - E-cigarettes and airways' disease: Behind the smokescreen.

PMID- 29052302
TI  - Variability of blood eosinophils as a biomarker in asthma and COPD.

PMID- 29052303
TI  - Catalytic Hydroalkylation of Allenes.
AB  - We have developed a catalytic method for the hydroalkylation of allenes using
      alkyl triflates as electrophiles and silane as a hydride source. The reaction has
      an excellent substrate scope and is compatible with a wide range of functional
      groups, including esters, aryl halides, aryl boronic esters, sulfonamides, alkyl
      tosylates, and alkyl bromides. We found evidence for a reaction mechanism that
      involves unusual dinuclear copper ally complexes as catalytic intermediates. The
      unusual structure of these complexes provides a rationale for their unexpected
      reactivity.

PMID- 29052304
TI  - Immunotherapy for hepatitis B in the direct acting antiviral era: Reevaluating
      the thymosin alpha1 efficacy trials in the light of a combination therapy
      approach.
AB  - Hepatitis B virus (HBV) causes both acute and chronic hepatitis and infects large
      numbers of individuals worldwide. Unfortunately, prediction of typical clinical
      outcome is problematic and there is considerable variability in the frequency,
      duration and severity of disease progression. The mainstay of HBV treatment is
      directed towards the suppression of HBV replication by nucleos(t)ide analogs
      (NUCs). The use of immunomodulators such as alpha-Interferon and thymosin alpha1
      can, in select patients, results in elimination of both HBsAg and HBeAg. Given
      the observation that viral clearance is most effective in the presence of a
      strong immune response, this review summarizes data suggesting that the use of a
      combination of an immune modulator such as Talpha1 with a highly effective NUC
      may result in a more successful therapeutic approach in patients with chronic
      hepatitis B (CHB). Results from small studies using combination Talpha1 and NUCs
      are encouraging, and ongoing clinical trials combining entecavir with Talpha1 are
      anticipated to provide important data assessing the use of a combination of
      Talpha1 with a NUC to achieve resolution of CHB.

PMID- 29052305
TI  - Pulmonary vascular indices and survival in left heart disease: illusion of
      conclusion?

PMID- 29052306
TI  - How 'healthy' do children really need to be? Going beyond the limits.

PMID- 29052308
TI  - An audit of ECT in England 2011-2015: Usage, demographics, and adherence to
      guidelines and legislation.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) continues to be used in England, but
      without comprehensive national auditing. Therefore, information was gathered on
      usage, demographics, consent, and adherence to the guidelines of the National
      Institute of Clinical Excellence (N.I.C.E.) and to the Mental Health Act. DESIGN
      AND METHODS: Freedom of Information Act requests were sent to 56 National Health
      Service Trusts. RESULTS: Thirty-two trusts provided some usable data. Only 10
      were able to report how many people received psychological therapy prior to ECT
      in accordance with N.I.C.E. recommendations, with figures ranging from 0% to
      100%. The number of people currently receiving ECT in England annually is between
      2,100 and 2,700, and falling. There was a 12-fold difference between the Trusts
      with the highest and lowest usage rates per capita. Most recipients are still
      women (66%) and over 60 (56%). More than a third (39%) is given without consent,
      with 30% of Trusts not adhering to mental health legislation concerning second
      opinions. At least 44% were not using validated measures of efficacy, and at
      least 33% failed to do so for adverse effects. Only four provided any actual data
      for positive outcomes or adverse effects. None provided any data on efficacy
      beyond the end of treatment. CONCLUSIONS: National audits should be reinstated.
      Independent, objective monitoring of adverse effects is urgently required. An
      investigation into why ECT is still administered excessively to older people and
      women seems long overdue. PRACTITIONER POINTS: Mental health staff should seek to
      ensure that all depressed people in their service are offered evidence-based
      psychological treatments before being offered E.C.T. Staff should lobby managers
      to ensure proper auditing of E.C.T. within their service Individuals receiving
      ECT should be closely monitored for adverse cognitive effects Overuse of ECT with
      women and older people should be avoided.

PMID- 29052307
TI  - Instrumental learning and cognitive flexibility processes are impaired in
      children exposed to early life stress.
AB  - Children who experience severe early life stress show persistent deficits in many
      aspects of cognitive and social adaptation. Early stress might be associated with
      these broad changes in functioning because it impairs general learning
      mechanisms. To explore this possibility, we examined whether individuals who
      experienced abusive caregiving in childhood had difficulties with instrumental
      learning and/or cognitive flexibility as adolescents. Fifty-three 14-17-year-old
      adolescents (31 exposed to high levels of childhood stress, 22 control) completed
      an fMRI task that required them to first learn associations in the environment
      and then update those pairings. Adolescents with histories of early life stress
      eventually learned to pair stimuli with both positive and negative outcomes, but
      did so more slowly than their peers. Furthermore, these stress-exposed
      adolescents showed markedly impaired cognitive flexibility; they were less able
      than their peers to update those pairings when the contingencies changed. These
      learning problems were reflected in abnormal activity in learning- and attention
      related brain circuitry. Both altered patterns of learning and neural activation
      were associated with the severity of lifetime stress that the adolescents had
      experienced. Taken together, the results of this experiment suggest that basic
      learning processes are impaired in adolescents exposed to early life stress.
      These general learning mechanisms may help explain the emergence of social
      problems observed in these individuals.

PMID- 29052309
TI  - Rapid weight gain during infancy and subsequent adiposity: a systematic review
      and meta-analysis of evidence.
AB  - The contribution of rapid weight gain (RWG) during infancy to later adiposity has
      received considerable investigation. The present systematic review and meta
      analysis aimed to update the literature on association between RWG and subsequent
      adiposity outcomes. Electronic searches were undertaken in EMBASE, MEDLINE,
      psycINFO, PubMed and ScienceDirect. Studies that examined the associations
      between RWG (a change in weight z-scores > 0.67) during infancy (from birth to
      age 2 years) and subsequent adiposity outcomes were included. Random effects meta
      analysis was conducted to obtain the weighted-pooled estimates of the odds of
      overweight/obesity for those with RWG. Seventeen studies were eligible for
      inclusion with the majority of studies (15/17) being of high/acceptable quality
      and reporting positive associations between RWG during infancy and later
      adiposity outcomes. RWG in infancy was associated with overweight/obesity from
      childhood to adulthood (pooled odds ratio = 3.66, 95% confidence interval: 2.59
      5.17, I2  > 75%). Subgroup analyses revealed that RWG during infancy was
      associated with higher odds of overweight/obesity in childhood than in adulthood,
      and RWG from birth to 1 year was associated with higher odds of
      overweight/obesity than RWG from birth to 2 years. The present study supports
      that RWG during infancy is a significant predictor of adiposity in later life.

PMID- 29052310
TI  - Effect of functionalized PHEMA micro- and nano-particles on the viscoelastic
      properties of fibrin-agarose biomaterials.
AB  - Two types of PHEMA-based particles, exhibiting either carboxyl or tertiary ammine
      functional groups, were incorporated to fibrin-agarose (FA) hydrogels, and the
      effect of the addition of these synthetic particles on the viscoelastic and
      microstructural properties of the biomaterials was evaluated. Experimental
      results indicated that the incorporation of both types of polymeric particles to
      FA scaffolds was able to improve the biomechanical properties of the biomaterials
      under steady state and oscillatory shear stresses, resulting in scaffolds
      characterized by higher values of the storage, loss, and shear moduli. In
      addition, the microstructural evaluation of the scaffolds showed that the
      nanoparticles exhibiting carboxyl functional groups were homogeneously
      distributed across the fibrous network of the hydrogels. The addition of both
      types of artificial polymeric particles was able to enhance the viscoelastic
      properties of the FA hydrogels, allowing the biomaterials to reach levels of
      mechanical consistency under shear stresses in the same range of some human
      native soft tissues, which could allow these biomaterials to be used as scaffolds
      for new tissue engineering applications. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 738-745, 2018.

PMID- 29052311
TI  - Functionalizing titanium surface with PAMAM dendrimer and human BMP2 gene via
      layer-by-layer assembly for enhanced osteogenesis.
AB  - The study reports on the gene functionalization of titanium substrates with
      multilayered functional human BMP2 (hBMP2) gene plasmid and its effects on
      osteogenesis in vitro and in vivo. The multilayers comprising cationic
      poly(amidoamine) (PAMAM) dendrimer/EGFP-hBMP2 plasmid DNA complex (d-DNA) and
      anionic naked plasmid were deposited on titanium substrates via layer-by-layer
      (LbL) assembly technique, which was revealed by atomic force microscopy (AFM),
      water contact angle measurement, and release profiles. The expression of marker
      gene EGFP and functional gene hBMP2 were observed in osteoblasts. The assays of
      alkaline phosphatase activity, collagen secretion, ECM mineralization, and
      osteogenesis-related genes expression indicated that the multilayered structure
      improved the osteogenic differentiation in vitro. Moreover, the femur and
      subcutaneous transplantation of multilayered titanium implants were also
      investigated to reveal osteogenesis peri-implant by using histological
      examination and X-ray imaging. The in vivo histologic results showed that the
      BMP2 group (containing functional gene hBMP2) resulted in improved osteogenic
      proteins expression in subcutaneous and femur tissue, as well as high level of
      bone formation and % bone-implant contact (%BIC) peri-implant. The study offers
      an effective dendrimer and hBMP2 based strategy for surface functionalization of
      titanium implants in potential orthopedic applications. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 706-717, 2018.

PMID- 29052313
TI  - The 50th Anniversary of the Abortion Act.

PMID- 29052314
TI  - Modeling the convergence accommodation of stereo vision for binocular endoscopy.
AB  - BACKGROUND: The stereo laparoscope is an important tool for achieving depth
      perception in robot-assisted minimally invasive surgery (MIS). METHODS: A dynamic
      convergence accommodation algorithm is proposed to improve the viewing experience
      and achieve accurate depth perception. Based on the principle of the human vision
      system, a positional kinematic model of the binocular view system is established.
      The imaging plane pair is rectified to ensure that the two rectified virtual
      optical axes intersect at the fixation target to provide immersive depth
      perception. RESULTS: Stereo disparity was simulated with the roll and pitch
      movements of the binocular system. The chessboard test and the endoscopic peg
      transfer task were performed, and the results demonstrated the improved disparity
      distribution and robustness of the proposed convergence accommodation method with
      respect to the position of the fixation target. CONCLUSIONS: This method offers a
      new solution for effective depth perception with the stereo laparoscopes used in
      robot-assisted MIS.

PMID- 29052312
TI  - Bleomycin-induced chromosomal damage and shortening of telomeres in peripheral
      blood lymphocytes of incident cancer patients.
AB  - Disruption of genomic integrity due to deficient DNA repair capacity and telomere
      shortening constitute hallmarks of malignant diseases. Incomplete or deficient
      repair of DNA double-strand breaks (DSB) is manifested by chromosomal aberrations
      and their frequency reflects inter-individual differences of response to exposure
      to mutagenic compounds. In this study, we investigated chromosomal integrity in
      peripheral blood lymphocytes (PBL) from newly diagnosed cancer patients,
      including 47 breast (BC) and 44 colorectal cancer (CRC) patients and 90 matched
      healthy controls. Mutagen sensitivity was evaluated by measuring chromatid breaks
      (CTAs) induced by bleomycin and supplemented by the chemiluminescent measurement
      of gamma-H2AX phosphorylation in 19 cancer patients (11 BC, 8 CRC). Relative
      telomere length (RTL) was determined in 22 BC, 32 CRC, and 64 controls. We
      observed statistically significant increased level of CTAs (P = .03) and
      increased percentage of aberrant cells (ACs) with CTAs (P = .05) in CRC patients
      compared with controls after bleomycin treatment. No differences were observed
      between BC cases and corresponding controls. CRC and BC patients with shorter RTL
      (below median) exhibited significantly higher amount of ACs (P = .02), CTAs (P =
      .02), and cells with high frequency of CTAs (>=12 CTAs/PBL; P = .03) after
      bleomycin treatment. No such associations were observed in healthy controls.
      gamma-H2AX phosphorylation after bleomycin treatment in PBL did not differ
      between CRC and BC patients. Our results suggest that altered DSB repair measured
      by sensitivity towards mutagen in PBL occurs particularly in CRC carcinogenesis.
      Irrespective of cancer type, telomere shortening may be associated with a
      decreased capacity to repair DSB.

PMID- 29052315
TI  - Identification and evolution of latrophilin receptor gene involved in Tribolium
      castaneum devolopment and female fecundity.
AB  - Latrophilins (LPHs) are adhesion G-protein-coupled receptors comprising three
      paralogous forms (LPH-1, LPH-2, and LPH-3) and known receptors for alpha
      latrotoxin, which are involved in growth, development, adaptability, and
      schizophrenia and other diseases in vertebrates. However, the functions of LPH
      are poorly understood in most insects. Here, phylogenetic and synteny analysis
      indicated that LPH-1 and LPH-3 evolved separately from a common ancestor LPH-2.
      Then, latrophilin (Tclph) was cloned in Tribolium castaneum, and three
      alternatively spliced transcripts (Tclpha, Tclphb and Tclphc) were identified.
      All these three Tclphs were highest expressed at the early adult stage, and
      strongly expressed in central nervous system of adults. Larval RNA interference
      (RNAi) against Tclph caused 24% adult wing abnormal, 30% insect death, and led to
      100% reductions in beetle fecundity. Fecundity deficiency was rescued by
      reciprocal crosses with wild-type females, but not males. And dissection results
      revealed that 63% of dsTclph female ovaries were atrophied. Further, exon
      specific RNAi illustrated that neither knockdown of Tclpha nor Tclphc resulted in
      development defects and reductions in beetle fecundity. Thus, it indicated that
      Tclphb was essential for development and female fecundity in T. castaneum.
      Moreover, Tclph knockdown increased the expression of the foxo, plc, and pka
      genes, which most likely modulated the effects of Tclph on development and
      reproduction in T. castaneum.

PMID- 29052316
TI  - Does an intervention designed to improve self-management, social support and
      awareness of palliative-care address needs of persons with heart failure, family
      caregivers and clinicians?
AB  - AIMS AND OBJECTIVES: To conduct a formative evaluation of the iPad-Enhanced
      Shared Care Intervention for Partners (iSCIP) among persons with heart failure
      (HF), family caregivers and clinicians. Together, persons with HF and family
      caregivers are referred to as partners. BACKGROUND: There is growing awareness of
      the caregiver's contributions to HF self-management, social support and
      reciprocal benefits of interventions that involve both partners. The iSCIP
      engages both partners in a six-session psychosocial intervention to address three
      preventable causes of poor outcomes in a HF population: poor self-management
      skills, inadequate social support and underutilisation of palliative care. An
      iPad app is used to organise the intervention. The goals of the iSCIP are to
      engage partners in HF self-management, communication about the HF patient's care
      values and preferences, and future planning. DESIGN: A qualitative focus group
      design was used. METHODS: Seven clinicians and eight partners participated in
      focus groups to explore their experiences, needs and reaction to the iSCIP
      content and technologies employed. Open-ended questions and closed-ended surveys
      were used to collect data. Deductive content analysis was used to analyse the
      qualitative data. NVivo software was used for qualitative data analysis. Bayesian
      statistical models were used to analyse numeric data. RESULTS: The iSCIP met
      partners' and clinicians' needs to improve self-management, communicate about
      care values and preferences and plan for the future. Quantitative analysis of
      numeric data supported our qualitative findings, in that both groups rated the
      intervention components useful to very useful. IMPLICATIONS FOR PRACTICE: These
      findings add to the growing evidence of the feasibility and acceptability of
      programs that address care values and preferences, and care planning. The iSCIP
      can be used as a guide for developing interventions and software applications,
      which involve both partners in care and palliative-care discussions.

PMID- 29052318
TI  - Proceedings of the 14th International Congress of the Spanish Association for
      Animal Reproduction (AERA), Barcelona, Spain, 9-11 November 2017.

PMID- 29052317
TI  - Defective ciliogenesis in INPP5E-related Joubert syndrome.
AB  - Joubert syndrome is a neurodevelopmental disorder, characterized by malformation
      of the mid and hindbrain leading to the pathognomonic molar tooth appearance of
      the brainstem and cerebellum on axial MRI. Core clinical manifestations include
      hypotonia, tachypnea/apnea, ataxia, ocular motor apraxia, and developmental delay
      of varying degrees. In addition, a subset of patients has retinal dystrophy,
      chorioretinal colobomas, hepatorenal fibrocystic disease, and polydactyly.
      Joubert syndrome exhibits genetic heterogeneity, with mutations identified in
      more than 30 genes, including INPP5E, a gene encoding inositol polyphosphate 5
      phosphatase E, which is important in the development and stability of the primary
      cilium. Here, we report the detailed clinical phenotypes of two sisters with a
      novel homozygous variant in INPP5E (NM_019892.4: c.1565G>C, NP_063945.2:
      p.Gly552Ala), expanding the phenotype associated with Joubert syndrome type 1.
      Expression studies using patient-derived fibroblasts showed changes in mRNA and
      protein levels. Analysis of fibroblasts from patients revealed that a significant
      number of cells had shorter or no cilia, indicating defects in ciliogenesis, and
      cilia maintenance.

PMID- 29052319
TI  - From pre-ovulatory follicle palpation to the challenge of twin pregnancies:
      Clinical reflections following one million gynaecological examinations in dairy
      cows.
AB  - CONTENTS: Based on experimental studies and extensive field-scale experience,
      this review offers new proposals for: (i) elevating the success of modern
      insemination procedures, (ii) emphasizing features of a pre-ovulatory follicle in
      the context of optimum insemination timing, (iii) overcoming heat stress and its
      consequences using physiological processes or endocrine protocols, (iv)
      establishing a viable pregnancy or early pregnancy loss and (v) the challenge of
      twin pregnancies. In conclusion, the fertility of high-yielding dairy cows can be
      further improved.

PMID- 29052320
TI  - Altrenogest treatment before weaning improves litter size in sows.
AB  - The study aimed to assess whether altrenogest treatment, fed before weaning (from
      -8 to -2 days), could improve fertility of sows showing reproductive seasonality.
      Ninety sows (50 in winter-spring [WS] and 40 in summer-autumn [SA]) were randomly
      selected and assigned to control (C; 27 in WS and 20 in SA) or altrenogest
      treatment (A; 23 in WS and 20 in SA) groups. The diameter and number of ovarian
      follicles were transrectally scanned at the onset of oestrus. Oestrus was
      evaluated twice daily from weaning to day 8 post-weaning. Sows in oestrus were
      post-cervically inseminated at 0 and 24 hr after the onset of oestrus with liquid
      stored semen (1.5 * 109 sperm/doses), and farrowing rates (FR) and total piglets
      born (LS) were recorded. More (p < .01) sows showed no signs of oestrus within 8
      days after weaning in SA (30%) than in WS (2%), without differences between A and
      C groups. The diameter (cm) of the follicles at the onset of oestrus was larger
      in A than in C sows (0.76 +/- 0.01 vs 0.73 +/- 0.01; p < .01), irrespective of
      the season. No differences in the number of follicles were found. FR did not
      differ between seasons and groups, being always above 85%. LS was larger (p <
      .01) in A (14.00 +/- 0.46) than C (12.27 +/- 0.44) sows, irrespective of the
      season. In conclusion, a short-term altrenogest treatment at the end of lactation
      improves the total number of piglets born from weaned sows, probably by promoting
      a better and more homogeneous follicular development at the start of oestrus.

PMID- 29052321
TI  - Coenzyme Q10 supplementation during in vitro maturation of bovine oocytes (Bos
      taurus) helps to preserve oocyte integrity after vitrification.
AB  - Oocyte vitrification causes less cell stress than slow cooling, but cytoskeletal
      and spindle alterations may occur affecting the oocyte competence. In vitro
      maturation (IVM) supplementation with different antioxidant molecules has been
      performed to attenuate this harmful stress. Coenzyme Q10 (CoQ10 ) supplementation
      has previously shown to have positive effects in bovine and mouse in vitro embryo
      development. The aim of this study was to evaluate the effects of CoQ10 during
      bovine oocyte IVM and vitrification. Cumulus-oocyte complexes (COCs) (n = 311)
      were cultured under standard maturation conditions with 0 MUM (control), 25 MUM
      and 50 MUM CoQ10 supplementation. After 22 hr, a cohort of 170 oocytes both from
      the control and from CoQ10 -supplemented groups were vitrified, warmed and
      returned to incubation until 24 hr of maturation, while the rest of the oocytes
      (n = 141) remained fresh. Then, oocyte survival was assessed morphologically by
      stereomicroscopy. Oocytes from all groups were then fixed and stained for
      assessing cortical granules (CG) migration and nuclear stage. High rates of
      oocyte MII progression and appropriate CG migration as a continuous layer beneath
      the plasma membrane were obtained both in control and in CoQ10 groups. Results
      showed that although vitrification has great impact in survival of IVM bovine
      oocytes, 50 MUM CoQ10 supplementation significantly improved oocyte survival (p =
      .045) and reduced the premature CG exocytosis, helping to preserve the CG
      migration pattern (31.3% control vs. 54.5% in 50 MUM CoQ10 ; p = .039),
      attenuating the negative effects of vitrification.

PMID- 29052323
TI  - Chitosan-dextran sulphate nanoparticles for GnRH release in rabbit insemination
      extenders.
AB  - This study was designed to develop chitosan (CS)-dextran sulphate (DS)
      nanoparticles containing a GnRH analogue and to study their effect on rabbit
      (Oryctolagus cuniculus) semen quality. Six experimental extenders were tested as
      follows: (control) Tris-citric acid-glucose (TCG), (1) 0.05% CS-0.05% DS (4:1),
      (2) 0.1% CS-0.05% DS (4:1), (3) 0.05% CS-0.05% DS (3:1), (4) 0.1% CS-0.05% DS
      (3:1), (5) 0.1% CS-0.05% DS (2:1). CS and DS were dissolved in TCG medium, and
      nanoparticles were obtained through magnetic stirring. Rabbit seminal samples
      were incubated up to 5 hr at 37 degrees C in the extenders, and seminal quality
      was evaluated. The entrapment efficiency was 40%-50%. After 5 hr at 37 degrees C,
      a 20% of the hormone was released. Results showed that the presence of CS-DS
      nanoparticles did not affect rabbit semen motility, viability and membrane
      functionality; however, acrosome integrity was significantly higher versus
      control (p < .001).

PMID- 29052324
TI  - Effect of heat stress during in vitro maturation on developmental competence of
      vitrified bovine oocytes.
AB  - Heat-shock protein 70 (HSP70) plays a crucial role as intracellular
      cytoprotectant and molecular chaperone. A phenomenon of heat stress (HS) leads to
      production of these proteins that could be beneficial to cells during
      cryopreservation, which is also a stressful process for the cell. This study
      aimed to evaluate the protective effect of exposure of bovine oocytes to moderate
      HS during in vitro maturation (IVM) prior vitrification. First, oocytes were
      subjected to HS (41.5 degrees C for 1 hr) at 0, 4, 8, 12 or 16 of IVM. Oocytes in
      vitro matured for 20 hr served as control group. Presence of HSP70 was detected
      at 20 hr by immunofluorescence. HSP70 expression was significantly higher when
      oocytes were subjected to HS at 8 hr of IVM. Next, oocytes were distributed into
      four groups: Control: IVM oocytes; VIT: oocytes vitrified/warmed at 20 hr of IVM;
      HS: oocytes subjected to HS at 8 hr of IVM; HS-VIT: oocytes subjected to HS at 8
      hr of IVM and vitrified/warmed at 20 hr of IVM. Oocytes were fertilized at 24 hr
      of IVM, and cleavage and blastocyst yield were assessed. No significant
      differences were observed among treatments when cleavage rate was evaluated.
      However, fresh control and HS oocytes resulted in a significantly higher (p <
      .05) blastocyst rate when compared to VIT and HS-VIT groups, although no
      significant differences within fresh or vitrified groups were observed. In
      conclusion, HS did not have a negative impact on the oocyte competence but HS
      applied before vitrification, offered no benefits for embryo development.

PMID- 29052325
TI  - First evidence for the presence of aquaporins in stallion sperm.
AB  - Aquaporins (AQPs) are transmembrane proteins found in all cells and are
      responsible for the transport of water and small solutes. While these proteins
      have been found in the spermatozoa of humans, rodents, pigs and cattle, where not
      only do they play a role for the regulation of sperm volume but are also related
      with the sperm resilience to withstand freeze-thawing procedures, their presence
      in stallion sperm is yet to be reported. Therefore, the objectives of this work
      were as follows: (i) to determine whether AQP3, AQP7 and AQP11 are present in
      stallion sperm and (ii) to investigate whether the relative amounts of these
      three AQPs play any role in the cryopreservation success. With this purpose, a
      total of five ejaculates from healthy stallions were collected. Evaluation of
      sperm quality and immunoblotting against these three proteins were performed
      before and after cryopreservation. Immunoblots confirmed the presence of AQP3,
      AQP7 and AQP11 in all examined samples. Subsequently, ejaculates were classified
      as GFE (good) and PFE (poor freezability ejaculates), according to their sperm
      viability and motility at 0 and 2 hr post-thaw. Relative AQP3 and AQP11 contents
      in stallion fresh semen were found to be significantly (p < .05) higher in GFE
      than in PFE. In conclusion, the current study has confirmed, for the first time,
      the presence of AQP3, AQP7 and AQP11 in stallion sperm. In addition, despite
      preliminary, our results suggest that AQP3 and AQP11 are involved in the
      resilience of stallion sperm to withstand cryopreservation. Ongoing research is
      aimed at increasing the sample size and includes immunolocalization studies.

PMID- 29052326
TI  - Effects of the antimicrobial peptide protegrine 1 on sperm viability and
      bacterial load of boar seminal doses.
AB  - The presence of bacteria adversely affects boar sperm quality of seminal doses
      intended for artificial insemination. Currently, the most common measure to
      prevent bacteriospermia is the addition of antibiotics in semen extenders;
      however, mounting evidence shows that microbial resistance exists. A promising
      alternative to replace antibiotics are antimicrobial peptides. In this study, the
      effects of the antimicrobial peptide protegrine 1 (PG1) on the sperm viability
      and bacterial load of boar seminal doses were evaluated. Three different
      concentrations of PG1 (2.5, 25 and 100 MUg/ml) were tested over a storing period
      of 10 days at 17 degrees C. Sperm viability was analysed by fluorescence
      microscopy (SYBR14/propidium iodide), and bacterial load was assessed by plating
      100 MUl of each sample in Luria-Bertani medium and incubated at 37 degrees C for
      72 hr under aerobic conditions. Protegrine 1 was effective in controlling the
      bacterial load in all the assessed concentrations (p < .05), reaching the lowest
      values at the highest concentrations of the antimicrobial peptide. Nevertheless,
      sperm viability was significantly (p < .05) reduced by all tested concentrations
      of this peptide, the most cytotoxic effects being observed at the highest PG1
      concentrations. Despite these results, the use of PG1 as an alternative to
      antibiotics cannot be totally discarded, as further studies using the truncated
      form of this peptide are needed.

PMID- 29052327
TI  - CRISPR is knocking on barn door.
AB  - Genome modification at specific loci in livestock species was only achievable by
      performing homologous recombination in somatic cells followed by somatic cell
      nuclear transfer. The difficulty and inefficiency of this method have slowed down
      the multiple applications of genome modification in farm animals. The discovery
      of site-specific endonucleases has provided a different and more direct route for
      targeted mutagenesis, as these enzymes allow the ablation (KO) or insertion (KI)
      of specific genomic sequences on a single step, directly applied to zygotes.
      Clustered regularly interspaced short palindromic repeats (CRISPR), the last site
      specific endonuclease to be developed, is a RNA-guided endonuclease, easy to
      engineer and direct to a given target site. This technology has been successfully
      applied to rabbits, swine, goats, sheep and cattle, situating genome editing in
      livestock species at an attainable distance, thereby empowering scientist to
      develop a myriad of applications. Genetically modified livestock animals can be
      used as biomodels to study human or livestock physiology and disease, as
      bioreactors to produce complex proteins, or as organ donors for transplantation.
      Specifically on livestock production, genome editing in farm animals may serve to
      improve productive genetic traits, to improve various animal products, to confer
      resistance to diseases or to minimize the environmental impact on farming. In
      this review, we provide an overview of the current methods for site-specific
      genome modification in livestock species, discuss potential and already developed
      applications of genome edition in farm animals and debate about the possibilities
      for approval of products derived from gene-edited animals for human consumption.

PMID- 29052328
TI  - Increased sperm cell production in ageing roosters by an oral treatment with an
      aromatase inhibitor and a natural herbal extract designed for improving
      fertility.
AB  - Rooster fertility peaks between 30 and 40 weeks of age and declines rapidly from
      50 weeks of age. This is linked to a reduction in the number of spermatozoa in
      the ejaculate due to high density of spermatids in the seminiferous tubules of
      low-fertility roosters. In this study, we assessed the effects over
      spermatogenesis of both letrozole, an aromatase inhibitor, and a commercial
      herbal extract designed for improving fertility composed by Tribulus, Cinnamomum,
      Zingiber and Sativus. Forty-two-week-old Ross 308 roosters (n = 24) were
      distributed into four groups: control, letrozole (0.03 mg/kg), herbal extract
      (0.04 ml/kg) and letrozole+herbal extract. After 14 weeks of daily oral
      supplementation, their testes and epididymides were weighed, fixed and sectioned
      for assessment of spermatogenesis and quantification of sperm cells inside the
      lumen. Differences in seminiferous tubules measurements and density of sperm
      cells were tested using R software (version 3.0.1). Although body weight was not
      affected by the treatment, testes from animals treated with the combination of
      letrozole and herbal extracts were heavier than those from control animals.
      Animals treated with either letrozole or herbal extract, or their combination,
      showed a significant higher number of sperm cells inside the seminiferous tubules
      and epididymis than control animals (p < .05). These data suggest that the use of
      letrozole and the herbal extract could improve sperm cell production in ageing
      roosters. Future studies are needed to disclose the causal mechanisms involved
      and its effect on fertility and ejaculate features.

PMID- 29052329
TI  - Voltage-dependent anion channel 2 is involved in in vitro capacitation of boar
      sperm.
AB  - Ion channels play an important role during sperm capacitation allowing the
      transport through plasma and mitochondrial membranes of specific molecules that
      are essential for the achievement of this physiologic status. Given that voltage
      dependent anion channel 2 (VDAC2) is present in boar spermatozoa and is known to
      be involved in calcium transport in somatic cells, this study aimed at
      determining whether it is implicated in sperm capacitation and the acrosome
      reaction. With this purpose, boar spermatozoa were capacitated in vitro for 4 hr,
      and acrosome reaction was induced with progesterone for a further hour, with or
      without the presence of two VDAC2-inhibitors (erastin and olesoxime) at two
      different concentrations (10 and 100 MUM). At different time points (0, 120, 240,
      270 and 300 min), an aliquot was taken and sperm motility, membrane integrity and
      lipid disorder were evaluated using computer-assisted sperm analysis and flow
      cytometry. The addition of the two inhibitors resulted in opposite effects. While
      erastin 100 MUM reduced the percentage of non-capacitated spermatozoa, the
      presence of olesoxime at the same concentration prevented the increase in
      membrane lipid disorder, which is a feature of sperm capacitation. Such
      prevention was concomitant with a maintaining effect on sperm membrane integrity
      evaluated through SYBR14/PI. Our results suggest that VDAC2 is involved in the
      regulation of sperm capacitation, despite the fact that the mechanisms through
      which erastin and olesoxime act are different.

PMID- 29052330
TI  - Aquaporins in the male reproductive tract and sperm: Functional implications and
      cryobiology.
AB  - Aquaporins (AQPs) play a vital role for the transport of water and solutes across
      cell membranes. Classification of these ubiquitous proteins into three categories
      (orthodox AQPs, aquaglyceroporins and superaquaporins) is based on their sequence
      similarity and substrate selectivity. In the male reproductive tract of mammals,
      most AQPs (except AQP6 and AQP12) are found in different organs (including
      testis, efferent ducts and epididymis). AQP1 and AQP9 are the most abundant AQPs
      in the efferent ducts and epididymis and play a crucial role for the
      secretion/reabsorption dynamics of luminal fluid during sperm transport and
      maturation. AQP3, AQP7, AQP8 and AQP11 are the most abundant AQPs in sperm and
      are involved in the regulation of their volume, which is required for the
      differentiation of spermatids into spermatozoa during spermatogenesis, as well as
      in sperm transit along environments of different osmolality (male and female
      reproductive tracts). While different studies conducted in oocytes and embryos
      have demonstrated that AQPs are important for cryotolerance, data in sperm are
      scarce. At present, mounting evidence indicates that AQP3, AQP7 and AQP11 are
      involved in the sperm response to variations of osmolality and to freeze-thawing
      procedures. All these studies contribute to understand the physiology of both
      male reproductive tract and sperm, and open up new research ventures on the
      improvement of sperm cryopreservation protocols.

PMID- 29052331
TI  - PIWIs, piRNAs and Retrotransposons: Complex battles during reprogramming in
      gametes and early embryos.
AB  - Gamete and embryo development are indispensable processes for successful
      reproduction. Cells involved in these processes acquire pluripotency, the ability
      to differentiate into multiple different cell types, through a series of events
      known as reprogramming that lead to profound changes in histone and DNA
      methylation. While essential for pluripotency, this epigenetic remodelling
      removes constraints that normally limit the expression of genomic sequences known
      as transposable elements (TEs). Unconstrained TE expression can lead to many
      deleterious consequences including infertility, so organisms have evolved complex
      and potent mechanistic arsenals to target and suppress TE expression during
      reprogramming. This review will focus on the control of transposable elements in
      gametes and embryos, and one important TE suppressing system known as the PIWI
      pathway. This broadly conserved, small RNA-targeted silencing mechanism appears
      critical for fertility in many species and may participate in multiple aspects of
      gene regulation in reproduction and other contexts.

PMID- 29052332
TI  - Effect of different extenders for donkey sperm vitrification in straws.
AB  - Aseptic vitrification of semen samples packed in straws has been successfully
      developed in human but not in donkeys. The aim of this study was to compare the
      effect of two extenders for donkey sperm vitrification using straws. Ejaculates
      from four Andalusian donkeys were collected, and samples were extended in INRA-96
      (I) or Gent (G) supplemented with sucrose 0.25 M and 1% bovine serum albumin
      (BSA). Extended samples were cooled for one hour at 5 degrees C. For
      vitrification, samples were filled in covered 0.25 ml straws and then plunged
      directly into liquid nitrogen. For warming, straws were immersed in INRA-96 at 43
      degrees C. Results showed no significant differences between I and G treatments
      for TM (34.2% +/- 8.7 vs. 30.7% +/- 9.6) and PM (26.8% +/- 7.3 vs. 24.6% +/-
      7.9), respectively. In conclusion, donkey sperm could be vitrified in straws
      either with INRA-96 or with Gent in combination with sucrose and BSA.

PMID- 29052334
TI  - Partner smoking influences whether mothers quit smoking during pregnancy: a
      prospective cohort study.
AB  - OBJECTIVE: To analyse the prevalence and intensity of smoking among pregnant
      women and their partners, and factors associated with quitting smoking among
      pregnant women. DESIGN: A prospective cohort study, starting in 2013. SETTING:
      Andalusia, the south of Spain. SAMPLE: A cohort of 486 healthy pregnant women
      followed-up on three occasions during pregnancy. METHODS: Estimation of the
      proportions of women and partners who quit smoking at each trimester. MAIN
      OUTCOME MEASURES: To determine factors associated in a multivariable model,
      considering sociodemographic, obstetric, anthropometric, lifestyle variables, and
      the smoking habits of their partners. RESULTS: A high proportion of women quit
      smoking during pregnancy (61.08%; 95% confidence interval, 95% CI 53.61-68.55%).
      The smoking rate amongst mothers decreased from 36.06% (n = 167) before pregnancy
      to 14.08% (n = 65), 12.39% (n = 54), and 11.92% (n = 51) during the three
      pregnancy trimesters (P < 0.001), and consumption decreased from 8.71
      cigarettes/day in the first trimester to 5.51 cigarettes/day in the second
      trimester (P < 0.001) and 5.96 cigarettes/day in third trimester (P = 0.0002
      first versus third trimester). There was only a minimal decrease in the frequency
      of smoking among the partners, however: 38.44% (n = 178) before pregnancy, and
      36.07% (n = 167), 32.72% (n = 143), and 31.85% (n = 136) during the three
      trimesters of pregnancy. The consumption of cigarettes did not decrease among
      partners: 11.75, 11.67, and 12.09 cigarettes/day (P = 0.4299 first versus second
      trimester; P = 0.654 first versus third trimester). Women whose partner smoked
      were less likely to quit (adjusted odds ratio, aOR 0.26; 95% CI 0.12-0.55).
      CONCLUSIONS: About one in ten pregnant women smoked and one in four was a passive
      smoker. Strategies to reduce tobacco exposure in pregnancy should include a focus
      on partner smoking. TWEETABLE ABSTRACT: Pregnant women quit smoking cigarettes in
      pregnancy. What about their partners?

PMID- 29052335
TI  - A comparative study on intrinsic fluorescence of BSA and lysozyme proteins in
      presence of different divalent ions from their solution and thin film
      conformations.
AB  - Optical emission behaviours of lysozyme and bovine serum albumin, from bulk and
      thin film geometry, were studied in the presence of three different divalent ions
      (Mg2+ , Ca2+ or Ba2+ ) using different spectroscopic [steady-state fluorescence,
      UV-Vis and Fourier transform infra-red (FTIR)] techniques. Additionally, protein
      thin films on silicon surfaces were prepared and morphological studies were
      carried out using atomic force microscopy. Dynamic quenching was mainly
      identified for both proteins in the presence of Mg2+ , Ca2+ and Ba2+ ions. The
      molecular conformation of the proteins was modified in thin films compared with
      that in solution, consequently quenching efficiencies also varied. ATR-FTIR
      studies confirmed the conformational changes of proteins in the presence of all
      divalent ions. All metal ions used were divalent in nature and belonged to the
      same group of the periodic table but, depending on their individual
      characteristics such as electron affinity, ionic radius, etc., the magnitude of
      the protein and hydrated ion interaction varied and accordingly the quenching
      efficiency was modified. Quenching was maximum for Ca2+ ions, followed by the
      other two ions. Our study clearly illustrates the geometry-dependent physical and
      biological functions of proteins.

PMID- 29052336
TI  - Radiographic and clinical outcomes of rooted, platform-switched, microthreaded
      implants with a sandblasted, large-grid, and acid-etched surface: A 5-year
      prospective study.
AB  - BACKGROUND: There is no data available on the long-term outcomes of a rooted,
      platform-switched, microthreaded implant with a sandblasted, large-grid, and acid
      etched surface. PURPOSE: This prospective, longitudinal study evaluated the
      clinical and radiographic outcomes of rooted, platform-switched, microthreaded
      and sandblasted, large-grid, and acid-etched (SLA) surface implants for 5 years.
      MATERIALS AND METHODS: Sixty implants were placed in sixty patients with
      partially edentulous maxillae or mandibles. The permanent prostheses were
      inserted 2-4 months after implant placement. Clinical and radiographic
      examinations were performed at follow-up visits scheduled postoperation,
      prosthesis installation, 1 year, and 5 years after surgery, to assess implant
      survival and success rates, biological and mechanical complications, and marginal
      bone loss. RESULTS: After 5 years' follow-up, four patients withdrawn from the
      study, and 56 implants achieved a 100% survival rate and 98.2% success rate.
      Three prosthetic complications occurred, resulting in a success rate for
      prostheses of 94.6%. The incidence of peri-implant mucositis was 9.1% and no peri
      implantitis was diagnosed. The average marginal bone loss at the mesial aspect
      was 0.46 +/- 0.27 mm after 1 year and 0.48 +/- 0.27 mm after 5 years. The average
      marginal bone loss at the distal aspect was 0.46 +/- 0.32 mm after 1 year and
      0.50 +/- 0.35 mm after 5 years. CONCLUSION: After 5 years of loading, the rooted,
      platform-switched, microthreaded, and SLA surface implants showed high survival
      and success rates, steady crestal bone levels, and excellent long-term clinical
      outcomes in the soft tissue. Overloading may be related to the marginal bone loss
      around implants, but the surgical protocol, different sites, and jaw position did
      not correlate with crestal bone loss.

PMID- 29052337
TI  - Magnetic stimulus responsive vancomycin drug delivery system based on chitosan
      microbeads embedded with magnetic nanoparticles.
AB  - Local antibiotic delivery can overcome some of the shortcomings of systemic
      therapy, such as low local concentrations and delivery to avascular sites. A
      localized drug delivery system (DDS), ideally, could also use external stimuli to
      modulate the normal drug release profile from the DDS to provide efficacious drug
      administration and flexibility to healthcare providers. To achieve this
      objective, chitosan microbeads embedded with magnetic nanoparticles were loaded
      with the antibiotic vancomycin and stimulated by a high frequency alternating
      magnetic field. Three such stimulation sessions separated by 1.5 h were applied
      to each test sample. The chromatographic analysis of the supernatant from these
      stimulated samples showed more than approximately 200% higher release of
      vancomycin from the DDS after the stimulation periods compared to nonstimulated
      samples. A 16-day long term elution study was also conducted where the DDS was
      allowed to elute drug through normal diffusion over a period of 11 days and
      stimulated on day 12 and day 15, when vancomycin level had dropped below
      therapeutic levels. Magnetic stimulation boosted elution of test groups above
      minimum inhibitory concentration (MIC), as compared to control groups (with no
      stimulation) which remained below MIC. The drug release from test groups in the
      intervals where no stimulation was given showed similar elution behavior to
      control groups. These results indicate promising possibilities of controlled drug
      release using magnetic excitation from a biopolymer-based DDS. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2169-2176,
      2018.

PMID- 29052333
TI  - Label-Free Quantitative Proteomic Analysis of Differentially Expressed Membrane
      Proteins of Pulmonary Alveolar Macrophages Infected with Highly Pathogenic
      Porcine Reproductive and Respiratory Syndrome Virus and Its Attenuated Strain.
AB  - Significant differences exist between the highly pathogenic (HP) porcine
      reproductive and respiratory syndrome virus (PRRSV) and its attenuated pathogenic
      (AP) strain in the ability to infect host cells. The mechanisms by which
      different virulent strains invade host cells remain relatively unknown. In this
      study, pulmonary alveolar macrophages (PAMs) are infected with HP-PRRSV (HuN4)
      and AP-PRRSV (HuN4-F112) for 24 h, then harvested and subjected to label-free
      quantitative MS. A total of 2849 proteins are identified, including 95 that are
      differentially expressed. Among them, 26 proteins are located on the membrane.
      The most differentially expressed proteins are involved in response to stimulus,
      metabolic process, and immune system process, which mainly have the function of
      binding and catalytic activity. Cluster of differentiation CD163, vimentin (VIM),
      and nmII as well as detected proteins are assessed together by string analysis,
      which elucidated a potentially different infection mechanism. According to the
      function annotations, PRRSV with different virulence may mainly differ in
      immunology, inflammation, immune evasion as well as cell apoptosis. This is the
      first attempt to explore the differential characteristics between HP-PRRSV and
      its attenuated PRRSV infected PAMs focusing on membrane proteins which will be of
      great help to further understand the different infective mechanisms of HP-PRRSV
      and AP-PRRSV.

PMID- 29052338
TI  - Laparoscopic transabdominal preperitoneal repair for strangulated inguinal
      hernia.
AB  - INTRODUCTION: Laparoscopic transabdominal preperitoneal repair (TAPP) is widely
      accepted in elective inguinal hernioplasty. However, given the scarcity of data,
      the feasibility and safety of TAPP in strangulated hernia cases have not yet been
      determined. METHODS: We retrospectively evaluated the data from a consecutive
      series of 33 patients who had undergone surgery for acute strangulated inguinal
      hernia associated with suspected visceral ischemic damage by either TAPP (TAPP
      group, n = 11) or conventional open hernioplasty via the anterior approach
      (anterior group, n = 22). RESULTS: The TAPP group had a significant longer
      surgical duration than the anterior group (147 vs 84 min) and relatively less
      blood loss. Incision and enlargement of the hernial orifice, which enables easy
      reduction of the strangulated organ, was performed in the last 7 of 11 cases in
      the TAPP group. The morbidity was lower in the TAPP group, but the difference was
      not statistically significant (18% vs 23%). The TAPP group had a significantly
      shorter postoperative hospital stay than the anterior group (7 vs 10 days).
      CONCLUSION: For surgeons with sufficient knowledge of the anatomy and expertise
      in reducing the strangulated organ, TAPP for strangulated inguinal hernia is at
      least comparable to open hernioplasty via the anterior approach in short-term
      outcomes.

PMID- 29052339
TI  - Structure-Activity and Stability Relationships for Cobalt Polypyridyl-Based
      Hydrogen-Evolving Catalysts in Water.
AB  - A series of eight new and three known cobalt polypyridyl-based hydrogen-evolving
      catalysts (HECs) with distinct electronic and structural differences are
      benchmarked in photocatalytic runs in water. Methylene-bridged bis-bipyridyl is
      the preferred scaffold, both in terms of stability and rate. For a cobalt complex
      of the tetradentate methanol-bridged bispyridyl-bipyridyl complex [CoII
      Br(tpy)]Br, a detailed mechanistic picture is obtained by combining
      electrochemistry, spectroscopy, and photocatalysis. In the acidic branch, a
      proton-coupled electron transfer, assigned to formation of CoIII -H, is found
      upon reduction of CoII , in line with a pKa (CoIII -H) of approximately 7.25.
      Subsequent reduction (-0.94 V vs. NHE) and protonation close the catalytic cycle.
      Methoxy substitution on the bipyridyl scaffold results in the expected cathodic
      shift of the reduction, but fails to change the pKa (CoIII -H). An analysis of
      the outcome of the benchmarking in view of this postulated mechanism is given
      along with an outlook for design criteria for new generations of catalysts.

PMID- 29052341
TI  - Response to "Lactation Status and Studies of Pyrimethamine Pharmacokinetics in
      Pregnancy".

PMID- 29052340
TI  - Absence of neurocognitive disadvantage associated with paediatric HIV subtype A
      infection in children on antiretroviral therapy.
AB  - INTRODUCTION: Infection with HIV subtype A has been associated with poorer
      neurocognitive outcomes compared to HIV subtype D in Ugandan children not
      eligible for antiretroviral therapy (ART). In this study, we sought to determine
      whether subtype-specific differences are also observed among children receiving
      ART. MATERIALS AND METHODS: Children were recruited from a clinical trial in
      which they were randomized to receive either lopinavir (LPV)- or non-nucleoside
      reverse transcriptase inhibitor (NNRTI)- based ART (NCT00978068). Age at
      initiation of ART ranged from six months to six years. HIV subtype was determined
      by PCR amplification and population sequencing of the pol region derived from
      peripheral blood mononuclear cell DNA, followed by application of the REGA and
      Recombinant Identification Programme algorithms. General cognition was assessed
      using the Kaufman Assessment Battery for Children (Second Edition), attention
      using the Test of Variables of Attention, and motor skills using the Bruininks
      Oseretsky Test of Motor Proficiency (Second Edition). Home environment was
      assessed using the Home Observation for the Measurement of the Environment
      (HOME). Age-adjusted test z-scores were entered into a regression model that
      adjusted for sex, socio-economic status score, HOME score, years of schooling,
      and ART treatment type. RESULTS: One hundred and five children were tested;
      median (interquartile range) age was 7.05 years (6.30 to 8.44), CD4 count was
      867.7 cells/mm3 (416.0 to 1203.5), and duration on ART was 4.03 years (3.55 to
      4.23). Seventy-eight children had HIV subtype A and 27 had subtype D; the groups
      had comparable home and socio-economic status, except that there were more males
      among children infected with subtype A than D (64.7% vs. 35.3%, p = 0.02). There
      were no differences between the subtypes in general cognition (estimated mean
      difference: 0.20; 95% CI: -0.11 to 0.50); p = 0.21), attention (-0.18, 95% CI: 
      0.60 to 0.24, p = 0.41) and motor skills (1.60, 95% CI: -0.84 to 4.04, p = 0.20).
      CONCLUSIONS: Our results imply that ART may diminish the neurocognitive
      disadvantage seen in treatment-naive HIV-infected children with subtype A.

PMID- 29052342
TI  - Supported housing for adults with psychiatric disabilities: How tenants confront
      the problem of loneliness.
AB  - The objective of this study was to examine the experience of loneliness among
      people with psychiatric disabilities after moving from custodial housing,
      including group homes, boarding homes, and family-type residences to independent,
      supported apartments in the community. Qualitative research methods guided by a
      naturalistic/constructivist framework were used. Data collection occurred between
      May 2014 and July 2015 and consisted of individual semi-structured interviews
      with 24 tenants residing in five supported housing sites across three Canadian
      provinces; interviews were also conducted with a designated family member for
      each tenant and with their service providers. Group interviews were conducted
      with housing workers in the five housing sites. The interviews were transcribed
      verbatim, codes generated and a thematic analysis undertaken using a
      constructivist approach. Results showed that for most tenants living in
      independent apartments with support loneliness was not a serious problem or was
      an issue that could be overcome. Most study participants viewed supported housing
      as preferable to custodial housing and as a normalising experience that
      facilitated community integration. While housing conditions, particularly those
      associated with congregate housing, sometimes helped attenuate loneliness among
      tenants, managing loneliness was primarily contingent on the ability of
      individuals to develop and maintain social connections, as well as on family
      involvement.

PMID- 29052343
TI  - Learning lessons from the analysis of patient complaints relating to staff
      attitudes, behaviour and communication, using the concept of emotional labour.
AB  - AIMS AND OBJECTIVES: This article explores the content of letters of complaint by
      patients and carers about the behaviour, attitudes and communication of
      healthcare staff. BACKGROUND: The most common focus of patient complaints in the
      UK and other high-income countries is staff attitudes, behaviour and
      communication. There is a move to learn lessons from patient complaints, which
      can be used to improve patient care and experience. METHODS: Fifty letters of
      complaint made by patients and carers relating to the behaviour, attitudes and
      communication of healthcare staff were analysed. RESULTS: Poor attitudes,
      behaviours and communication have significant negative impact on the emotional
      well-being of patients and carers. Many patients and carers have heightened
      sensitivities due to both health-related stresses and also other factors. The
      healthcare role is expected to include compassion and kindness. The concept of
      emotional labour is useful in explaining the skills and effort required of staff
      in this often invisible and undervalued aspect of health care. CONCLUSIONS: Given
      the increasing focus on patient experience, it is important that the importance
      of good staff attitudes, behaviours and communication is understood and that the
      emotional labour associated with this is recognised. RELEVANCE TO CLINICAL
      PRACTICE: An understanding of emotional intelligence can protect staff from
      burnout and other negative outcomes which those in a caring role can experience.

PMID- 29052344
TI  - Brief counselling after home-based HIV counselling and testing strongly increases
      linkage to care: a cluster-randomized trial in Uganda.
AB  - INTRODUCTION: The aim of this study was to determine whether counselling provided
      subsequent to HIV testing and referral for care increases linkage to care among
      HIV-positive persons identified through home-based HIV counselling and testing
      (HBHCT) in Masaka, Uganda. METHODS: The study was an open-label cluster
      randomized trial. 28 rural communities were randomly allocated (1:1) to
      intervention (HBHCT, referral and counselling at one and two months) or control
      (HBHCT and referral only). HIV-positive care-naive adults (>=18 years) were
      enrolled. To conceal participants' HIV status, one HIV-negative person was
      recruited for every three HIV-positive participants. Primary outcomes were
      linkage to care (clinic-verified registration for care) status at six months, and
      time to linkage. Primary analyses were intention-to-treat using random effects
      logistic regression or Cox regression with shared frailty, as appropriate.
      RESULTS: Three hundred and two(intervention, n = 149; control, n = 153) HIV
      positive participants were enrolled. Except for travel time to the nearest HIV
      clinic, baseline participant characteristics were generally balanced between
      trial arms. Retention was similar across trial arms (92% overall). One hundred
      and twenty-seven (42.1%) participants linked to care: 76 (51.0%) in the
      intervention arm versus 51 (33.3%) in the control arm [odds ratio = 2.18, 95%
      confidence interval (CI) = 1.26-3.78; p = 0.008)]. There was evidence of
      interaction between trial arm and follow-up time (p = 0.009). The probability of
      linkage to care, did not differ between arms in the first two months of follow
      up, but was subsequently higher in the intervention arm versus the control arm
      [hazard ratio = 4.87, 95% CI = 1.79-13.27, p = 0.002]. CONCLUSIONS: Counselling
      substantially increases linkage to care among HIV-positive adults identified
      through HBHCT and may enhance efforts to increase antiretroviral therapy coverage
      in sub-Saharan Africa.

PMID- 29052346
TI  - Single-incision laparoscopic cholecystectomy for gallbladder torsion: A case
      report and literature review.
AB  - We present a case of preoperatively diagnosed gallbladder torsion (GT) that was
      successfully treated by single-incision laparoscopic cholecystectomy. An 80-year
      old woman presented with sudden pain and a palpable mass in the right upper
      quadrant. Contrast-enhanced CT revealed ischemic changes, a swollen gallbladder
      with a V-shaped distortion of the extrahepatic ducts, and the gallbladder in an
      abnormal anatomical position; clinical findings indicated GT. We performed single
      incision laparoscopic cholecystectomy and intraoperatively found that the
      floating gallbladder was twisted counterclockwise by 180 degrees  around the
      cystic duct. After an uneventful postoperative course, the patient was discharged
      on postoperative day 7. Laparoscopic cholecystectomy for a GT was first performed
      in 1994, and since then, 28 cases, including ours, have been treated
      laparoscopically. Laparoscopic cholecystectomy for GT could be the standard
      treatment for this condition, and single-incision laparoscopic cholecystectomy
      may be a good surgical option for patients with GT because of its anatomical
      characteristics.

PMID- 29052345
TI  - Views of diverse primary care patients on the roles of healthcare providers and
      staff and the influence of other variables in their weight management.
AB  - The prevalence of overweight/obesity is disproportionately higher among
      racial/ethnic minority and low-income patients. The purpose of this study was to
      survey racially diverse, low-income patients regarding their experiences with and
      desires regarding their providers' involvement in weight management. Adult
      patients (N = 529), including mostly African American (42.7%), White (44.6%) and
      low-income (55.5% with incomes <$30 000) patients from 7 Patient-Centered Medical
      Homes voluntarily completed a brief anonymous survey while waiting to see their
      providers. Only 19.8% of the patients said that their primary care provider
      frequently or very frequently talked with them about their weight. Older patients
      as compared to younger patients, as well as males compared to females, were more
      likely to have their primary care provider talk to them about their diet and
      physical activity during the last year. It was also found that 56.9% of the
      patients were interested in getting help from their doctor to connect with
      resources for weight management in their community. African American patients, as
      compared to White patients, were more interested in getting such help. These
      results suggest that there is a need to establish healthcare policies and
      training in primary care settings that are designed to ensure that primary care
      providers routinely talk with all of their patients, including their female and
      older patients, about their weight and weight management services. Additionally,
      primary care administrators need to play an increased role in identifying,
      developing, and advocating for affordable weight management services,
      particularly in African American and low-income communities.

PMID- 29052347
TI  - Meta-analysis of test accuracy studies using imputation for partial reporting of
      multiple thresholds.
AB  - INTRODUCTION: For tests reporting continuous results, primary studies usually
      provide test performance at multiple but often different thresholds. This creates
      missing data when performing a meta-analysis at each threshold. A standard meta
      analysis (no imputation [NI]) ignores such missing data. A single imputation (SI)
      approach was recently proposed to recover missing threshold results. Here, we
      propose a new method that performs multiple imputation of the missing threshold
      results using discrete combinations (MIDC). METHODS: The new MIDC method imputes
      missing threshold results by randomly selecting from the set of all possible
      discrete combinations which lie between the results for 2 known bounding
      thresholds. Imputed and observed results are then synthesised at each threshold.
      This is repeated multiple times, and the multiple pooled results at each
      threshold are combined using Rubin's rules to give final estimates. We compared
      the NI, SI, and MIDC approaches via simulation. RESULTS: Both imputation methods
      outperform the NI method in simulations. There was generally little difference in
      the SI and MIDC methods, but the latter was noticeably better in terms of
      estimating the between-study variances and generally gave better coverage, due to
      slightly larger standard errors of pooled estimates. Given selective reporting of
      thresholds, the imputation methods also reduced bias in the summary receiver
      operating characteristic curve. Simulations demonstrate the imputation methods
      rely on an equal threshold spacing assumption. A real example is presented.
      CONCLUSIONS: The SI and, in particular, MIDC methods can be used to examine the
      impact of missing threshold results in meta-analysis of test accuracy studies.

PMID- 29052350
TI  - Platelet lysate activates quiescent cell proliferation and reprogramming in human
      articular cartilage: Involvement of hypoxia inducible factor 1.
AB  - The idea of rescuing the body self-repair capability lost during evolution is
      progressively gaining ground in regenerative medicine. In particular, growth
      factors and bioactive molecules derived from activated platelets emerged as
      promising therapeutic agents acting as trigger for repair of tissue lesions and
      restoration of tissue functions. Aim of this study was to assess the potential of
      a platelet lysate (PL) for human articular cartilage repair considering its
      activity on progenitor cells and differentiated chondrocytes. PL induced the re
      entry in the cell cycle of confluent, growth-arrested dedifferentiated/progenitor
      cartilage cells. In a cartilage permissive culture environment, differentiated
      cells also resumed proliferation after exposure to PL. These findings correlated
      with an up-regulation of the proliferation/survival pathways ERKs and Akt and
      with an induction of cyclin D1. In short- and long-term cultures of articular
      cartilage explants, we observed a release of proliferating chondroprogenitors
      able to differentiate and form an "in vitro" tissue with properties of healthy
      articular cartilage. Moreover, in cultured cartilage cells, PL induced a hypoxia
      inducible factor (HIF-1) alpha increase, its nuclear relocation and the binding
      to HIF-1 responsive elements. These events were possibly related to the cell
      proliferation because the HIF-1 inhibitor acriflavine inhibited HIF-1 binding to
      HIF-1 responsive elements and cell proliferation. Our study demonstrates that PL
      induces quiescent cartilage cell activation and proliferation leading to new
      cartilage formation, identifies PL activated pathways playing a role in these
      processes, and provides a rationale to the application of PL for therapeutic
      treatment of damaged articular cartilage.

PMID- 29052348
TI  - Shank3-deficient rats exhibit degraded cortical responses to sound.
AB  - : Individuals with SHANK3 mutations have severely impaired receptive and
      expressive language abilities. While brain responses are known to be abnormal in
      these individuals, the auditory cortex response to sound has remained largely
      understudied. In this study, we document the auditory cortex response to speech
      and non-speech sounds in the novel Shank3-deficient rat model. We predicted that
      the auditory cortex response to sounds would be impaired in Shank3-deficient
      rats. We found that auditory cortex responses were weaker in Shank3 heterozygous
      rats compared to wild-type rats. Additionally, Shank3 heterozygous responses had
      less spontaneous auditory cortex firing and were unable to respond well to rapid
      trains of noise bursts. The rat model of the auditory impairments in SHANK3
      mutation could be used to test potential rehabilitation or drug therapies to
      improve the communication impairments observed in individuals with Phelan
      McDermid syndrome. Autism Res 2018, 11: 59-68. (c) 2017 International Society for
      Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with SHANK3
      mutations have severely impaired language abilities, yet the auditory cortex
      response to sound has remained largely understudied. In this study, we found that
      auditory cortex responses were weaker and were unable to respond well to rapid
      sounds in Shank3-deficient rats compared to control rats. The rat model of the
      auditory impairments in SHANK3 mutation could be used to test potential
      rehabilitation or drug therapies to improve the communication impairments
      observed in individuals with Phelan-McDermid syndrome.

PMID- 29052349
TI  - Relationship between UGT1A1*27 and UGT1A1*7 polymorphisms and irinotecan-related
      toxicities in patients with lung cancer.
AB  - BACKGROUND: The objective of this study was to evaluate the effects of gene
      polymorphisms, including UGT1A1*7, *27, and *29, on the safety of irinotecan
      therapy. METHODS: The eligibility criteria were: lung cancer patients scheduled
      to undergo irinotecan therapy, aged >= 20 years, with a performance status of 0
      2. Thirty-one patients were enrolled and their blood was collected and used to
      examine the frequency of UGT1A1*6, *7, *27, *28, and *29 polymorphisms and the
      concentrations of irinotecan, SN-38, and SN-38G after irinotecan therapy.
      RESULTS: The patients' characteristics were as follows: male/female 25/6, median
      age 71 years (range 55-84), stage IIB/IIIA/IIIB/IV 2/6/11/12, and
      adenocarcinoma/squamous cell carcinoma/small cell carcinoma/other 14/10/3/4,
      respectively. The -/-, *6/-, *7/-, *27/-, *28/-, and *29/- UGT1A1 gene
      polymorphisms were observed in 10 (32%), 10 (32%), 2 (6%), 2 (6%), 7 (23%), and 0
      (0%) cases, respectively. The UGT1A1*27 polymorphism occurred separately from the
      UGT1A1*28 polymorphism. The lowest leukocyte counts of the patients with the
      UGT1A1*27 and UGT1A1*6 gene polymorphisms were lower than those observed in the
      wild-type patients. SN-38 tended to remain in the blood for a prolonged period
      after the infusion of irinotecan in patients with UGT1A1*27 or UGT1A1*28
      polymorphisms. No severe myelotoxicity was seen in the patients with UGT1A1*7.
      CONCLUSION: UGT1A1*27 can occur separately from UGT1A1*28 and is related to
      leukopenia during irinotecan treatment. UGT1A1*7 is less relevant to irinotecan
      induced toxicities, and UGT1A1*29 seems to have little clinical impact.

PMID- 29052351
TI  - Analysis of the clinical features of invasive bronchopulmonary aspergillosis.
AB  - INTRODUCTION: Early diagnosis of invasive bronchopulmonary aspergillosis (IBPA)
      is difficult, so the mortality rate is high. OBJECTIVE: To discuss the clinical
      features of IBPA. METHODS: We retrospectively analyzed the clinical features,
      imaging findings, laboratory test, diagnosis and treatment of 115 patients with
      IBPA diagnosed from October 2004 to June 2013 in Zhongshan Hospital, Fudan
      University. RESULTS: The main clinical manifestations were cough in 58 patients
      (50.4%), expectoration in 37 patients (32.2%), fever in 18 patients (15.7%),
      shortness of breath in 26 patients (22.6%), hemoptysis in 26 patients (22.6%) and
      chest pain in 7 patients (6.0%). The main CT findings were nodules in 35 patients
      (30.4%), consolidation shadows or patchy shadows in 62 patients (53.9%) and
      cavity in 14 patients (12.2%). Percutaneous pulmonary biopsy was conducted in 25
      patients (21.7%), TBLB in 58 patients (50.4%) and thoracoscopic surgery in 32
      patients (27.8%). The positive rate of GM test was 73.5% (72/98). Thirty patients
      who received lobectomy were followed up for 1-3 years. Fifty-five patients who
      received monotherapy with antifungal agents were followed up for 1-3 years, and
      12 patients were healed. The lesions for 23 patients were obviously absorbed, 10
      patients had aggravation and two patients died. CONCLUSIONS: The clinical
      manifestations of IBPA were unspecific. The main symptoms were cough and
      expectorate. Patients with different immunologic function had different imaging
      findings. The halo sign and new moon sign for diagnosis was not as common as
      reported. Interventional therapy under bronchoscope is very important for
      patients with ATB.

PMID- 29052352
TI  - Microbial contamination of open-but-unused portions of wound dressings stored in
      home settings.
AB  - The purpose of this study was to investigate incidence rates and levels of
      microbial contamination in open-but-unused portions of wound dressings stored in
      home settings. Portions of wound dressings were collected at up to four home
      visits for 104 clients undertaking wound management within their home. A control
      sample and stored sample was collected on each home visit and sent for pathology
      testing to identify levels of microbial contamination. The stored open-but-unused
      wound dressings were managed according to a written protocol. Of the tested
      samples (n = 776), 6% of control samples and 7% of test samples had microbial
      contamination. From regression analysis, the stored samples were more likely to
      have microbial contamination than control samples, but results were not
      statistically significant. In comparing occasions of storage and handling across
      four home visits, after adjusting for sample group and dressing type, none of the
      home visit occasion regressions were statistically significant. In conclusion,
      storage of open-but-unused portions of wound dressings kept in home settings does
      not appear to increase the rate of microbial contamination compared to newly
      opened wound dressings.

PMID- 29052353
TI  - Living with an indwelling urethral catheter in a community setting: Exploring
      triggers for unscheduled community nurse "out-of-hours" visits.
AB  - AIMS AND OBJECTIVE: To explore the experiences of community patients living with
      a urethral catheter and those caring for them. BACKGROUND: Living at home with an
      indwelling urethral catheter often results in consequences that create a double
      edged burden: first, on patients and their relative carers and second, in terms
      of unscheduled community nurse service "out-of-hours" provision. DESIGN: One-to
      one interviews were conducted with patients living at home, their relative
      carers, qualified community nurses, augmented home carers and healthcare
      assistant. Quantitative data in relation to frequency, duration and reason for
      visits were extracted from the community nurse "out-of-hours" service database.
      RESULTS: Quantitative data showed that 20% of all community nurses unscheduled
      "out-of-hours" visits were triggered by an indwelling urethral catheter
      consequence. Qualitative data revealed that health and social care staff felt
      knowledgeable and skilled in urethral catheter management. Conversely, patients
      and relative carers felt poorly equipped to manage the situation when something
      went wrong. The majority of patients described the catheter as being a
      debilitating source of anxiety and pain that reduced their quality of life.
      CONCLUSION: Urethral catheter complications are frequent and impact seriously on
      quality of life with informal carers also affected. Community nurses experienced
      frequent unscheduled visits. Patients often feel isolated as well as lacking in
      knowledge, skills and information on catheter management. Having better urethral
      catheter information resources could increase patient and relative carer
      confidence, encourage self-care and problem solving, as well as facilitate
      meaningful consistent dialogue between patients and those who provide them with
      help and support. RELEVANCE TO CLINICAL PRACTICE: Better patient information
      resources regarding urethral catheter management have potential to improve
      patient and relative carer quality of life and reduce service provision burden.

PMID- 29052354
TI  - Revisiting the Ancylostoma Caninum Secretome Provides New Information on Hookworm
      Host Interactions.
AB  - Hookworm infection is a major tropical parasitic disease affecting almost 500
      million people worldwide. These soil-transmitted helminths can survive for many
      years in the intestine of the host, where they feed on blood, causing iron
      deficiency anemia and other complications. These parasites release a variety of
      molecules known as excretory/secretory products (ESPs) that are involved in many
      different biological processes that govern parasite survival. Using a combination
      of separation techniques such as SDS-PAGE and OFFGEL electrophoresis, in
      combination with state-of-the-art mass spectrometry we have reanalyzed the dog
      hookworm, Ancylostoma caninum, ESPs (AcESP). We identified 315 proteins present
      in the AcESP, compared with just 105 identified in previous studies. The most
      highly represented family of proteins is the SCP/TAPs (110 of the 315 proteins),
      and the most abundant constituents of AcESP are homologues of the tissue
      inhibitors of metalloproteases (TIMP) family. Interestingly, we identified new
      homologs of well-known vaccine candidates and immunomodulatory proteins. This
      study provides novel information about the proteins secreted by A. caninum, and
      constitutes a comprehensive dataset to study the proteins involved in host
      hookworm interactions.

PMID- 29052355
TI  - Using the SAPAS to identify risk for personality disorders among psychiatric
      outpatients in India: A feasibility study.
AB  - Personality disorders (PDs) are common among psychiatric outpatients and are
      associated with increased morbidity and worse treatment outcomes. Epidemiological
      research conducted among this population in Asian countries is limited,
      reflecting a significant gap in the current literature. One barrier to this
      research is the lack of appropriate screening tools. The current research
      assessed the feasibility of using the SAPAS (Standardized Assessment of
      Personality-Abbreviated Scale) screening tool to identify individuals at high
      risk of PD in an Indian psychiatric outpatient population and provides an initial
      estimate of PD prevalence by using a validated diagnostic interview, the ICD-10
      International Personality Disorder Examination. The findings suggest that whilst
      use of the SAPAS was feasible, acceptable to patients and led to clinically
      useful findings, when using the recommended cut-off score of 4, the SAPAS largely
      overdiagnoses the risk for PD in psychiatric outpatients in India (positive
      predictive value = 26.3%). The estimated prevalence of personality disorder in
      the sample was 11.1%, based on administering the International Personality
      Disorder Examination diagnostic interview to high-risk patients scoring 4 and
      above on the SAPAS, which is higher than previous estimates for this population
      and still likely to be an underestimation. Future studies should translate the
      measure into Bengali and evaluate its sensitivity and specificity at different
      cut-off points in order to optimize its use in Indian populations. Copyright (c)
      2017 John Wiley & Sons, Ltd.

PMID- 29052356
TI  - In-vitro biocompatibility, bioactivity and photoluminescence properties of Eu3+
      /Sr2+ dual-doped nano-hydroxyapatite for biomedical applications.
AB  - In the present investigation, we have successfully synthesized luminescent Eu3+ 
      doped and Eu3+ /Sr2+ codoped hydroxyapatite (HA) nanoparticles through sol-gel
      assisted precipitation method with the aim of developing novel biomaterials
      containing osteoblast mineral (Sr2+ ) and luminescence activator (Eu3+ ). The
      structure, morphology, thermal stability, and luminescence properties of the
      resultant spherical nanoparticles (50-100 nm diameters) were studied. Moreover,
      the in-vitro bioactivity of Eu0.1 Sr0.1 HA nanoparticles was investigated by
      immersing in the simulated body fluid for many weeks. The antimicrobial activity
      results against gram positive and gram negative bacterial stains, showed better
      resistivity for the Eu0.1 Sr0.1 HA among the other compositions. The MTT [3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay of live/dead cells
      cultured with Eu3+ /Sr2+ -doped HA nanoparticles retained its normal morphology
      and did not show a significant impact on cell proliferation at various incubation
      days, which evidence for the material's superior biocompatible nature even at a
      higher concentration of 375 ug/mL. Thus, the incorporation of dual ions in HA
      nanoparticles with strong luminescence properties develops potential biomaterial
      for live cell imaging and in nanomedicine. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 106B: 2191-2201, 2018.

PMID- 29052358
TI  - Outcome standardisation - next rung in the ladder for perinatal epidemiology.

PMID- 29052357
TI  - Critical-sized full-thickness skin defect regeneration using ovine small
      intestinal submucosa with or without mesenchymal stem cells in rat model.
AB  - Decellularized extracellular matrices (ECM) based materials are routinely used
      for a variety of clinical applications. Hereof, in vivo application of
      decellularized ovine small intestinal submucosal (DOSIS) layer as, a scaffold is
      yet to be investigated. In this study, the effectiveness of the DOSIS scaffold,
      with or without rat bone marrow mesenchymal stem cells (BM-MSCs), in full
      thickness wound healing of critical-sized defect was experimentally studied in a
      rat model. The experimental groups included; group I (control), group II (DOSIS),
      and group III (BM-MSCs-seeded DOSIS). Wound healing of all groups was examined
      and compared clinically and histopathologically on days 7, 14, and 21
      postoperation. Our results represented BM-MSCs-seeded DOSIS accelerated wound
      contraction and healing compared to both the DOSIS alone and control groups.
      Epithelization was close to completion 21 days postoperation in DOSIS alone. In
      OSIS with BM-MSCs group, epithelization was faster and had fully taken place at
      the subsequent time points. DOSIS layer, as cell-free form with low substantially
      DNA content, accelerated healing of rat skin wound defects that was created at
      critical-size and full-thickness. In conclusion, decellularized OSIS alone and in
      combination with BM-MSCs has the potential to be used as a wound graft material
      in skin regenerative medicine. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
      Res Part B: Appl Biomater, 106B: 2177-2190, 2018.

PMID- 29052359
TI  - Authors' reply re: Cranberry capsules to prevent nosocomial urinary tract
      bacteriuria after pelvic surgery: a randomised controlled trial.

PMID- 29052360
TI  - Should the HFEA be regulating the add-on treatments for IVF/ICSI in the UK?: FOR:
      Regulation of the fertility add-on treatments for IVF.

PMID- 29052361
TI  - Re: Cranberry capsules to prevent nosocomial urinary tract bacteriuria after
      pelvic surgery: a randomised controlled trial: Cranberry for prevention of
      bacteriuria?

PMID- 29052363
TI  - Should the HFEA be regulating the add-on treatments for IVF/ICSI in the UK?:
      AGAINST: HFEA regulation of add-on IVF/ICSI.

PMID- 29052364
TI  - Sensorimotor learning and associated visual perception are intact but unrelated
      in autism spectrum disorder.
AB  - : Humans show an astonishing capability to learn sensorimotor behaviours.
      However, data from sensorimotor learning experiments suggest the integration of
      efferent sensorimotor commands, afferent sensorimotor information, and visual
      consequences of a performed action during learning is different in autism,
      leading to atypical representation of internal action models. Here, we
      investigated the generalization of a sensorimotor internal action model formed
      during sensorimotor learning to a different, but associated, visual perception
      task. Although motor timing was generally less accurate in adults with autism,
      following practice with feedback both autistic adults, and controls,
      significantly improved performance of the movement sequence timing task by
      reducing timing error. In a subsequent perception task, both groups demonstrated
      similar temporal-discrimination accuracy (autism = 75%; control = 76%).
      Significant correlations between motor timing error, and temporal-discrimination
      during a perception task, was found for controls. No significant correlations
      were found for autistic adults. Our findings indicate that autistic adults
      demonstrated adaptation by reducing motor timing error through sensorimotor
      learning. However, the finding of significant correlations between motor timing
      error and temporal-discrimination accuracy in the control group only suggests
      sensorimotor processes underpinning internal action model formation operate
      differently in autism. Autism Res 2018, 11: 296-304. (c) 2017 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We showed
      autistic adults learned a new motor skill, and visually judged moving objects, to
      a similar level of accuracy as a control group. Unlike the control group, there
      was no relationship between how well autistic adults learned the motor skill, and
      how well they judged objects. The lack of a relationship might be one of the
      reasons autistic adults interact differently in the social world.

PMID- 29052366
TI  - Corrigendum: Simultaneous Multiple MS Binding Assays Addressing D1 and D2
      Dopamine Receptors.

PMID- 29052365
TI  - Inferior In Vivo Osteogenesis and Superior Angiogeneis of Human Adipose Tissue: A
      Comparison with Bone Marrow-Derived Stromal Stem Cells Cultured in Xeno-Free
      Conditions.
AB  - The possibility of using adipose tissue-derived stromal cells (ATSC) as
      alternatives to bone marrow-derived stromal cells (BMSC) for bone repair has
      garnered interest due to the accessibility, high cell yield, and rapid in vitro
      expansion of ATSC. For clinical relevance, their bone forming potential in
      comparison to BMSC must be proven. Distinct differences between ATSC and BMSC
      have been observed in vitro and comparison of osteogenic potential in vivo is not
      clear to date. The aim of the current study was to compare the osteogenesis of
      human xenofree-expanded ATSC and BMSC in vitro and in an ectopic nude mouse model
      of bone formation. Human MSC were implanted with biphasic calcium phosphate
      biomaterials in subcutis pockets for 8 weeks. Implant groups were: BMSC, ATSC,
      BMSC and ATSC mixed together in different ratios, as well as MSC primed with
      either osteogenic supplements (250 MUM ascorbic acid, 10 mM beta
      glycerolphosphate, and 10 nM dexamethasone) or 50 ng/ml recombinant bone
      morphogenetic protein 4 prior to implantation. In vitro results show osteogenic
      gene expression and differentiation potentials of ATSC. Despite this, ATSC failed
      to form ectopic bone in vivo, in stark contrast to BMSC, although osteogenic
      priming did impart minor osteogenesis to ATSC. Neovascularization was enhanced by
      ATSC compared with BMSC; however, less ATSC engrafted into the implant compared
      with BMSC. Therefore, in the content of bone regeneration, the advantages of ATSC
      over BMSC including enhanced angiogenesis, may be negated by their lack of
      osteogenesis and prerequisite for osteogenic differentiation prior to
      transplantation. Stem Cells Translational Medicine 2017;6:2160-2172.

PMID- 29052367
TI  - Decellularized caprine liver extracellular matrix as a 2D substrate coating and
      3D hydrogel platform for vascularized liver tissue engineering.
AB  - Development of a vascularized liver tissue construct is a need of an hour to
      circumvent the current demand of liver transplantation in health care sector. An
      appropriate matrix must support liver cell viability, functionality, and
      development of microvasculature. With this perspective, here, we report the use
      of decellularized caprine liver extracellular matrix (CLECM) derived hydrogel for
      tissue engineering applications. First, CLECM was used as a substrate coating
      material for 2D hepatocyte culture. HepG2 cells cultured on CLECM-coated surface
      showed higher albumin, urea, glycogen, and GAGs synthesis in comparison with
      collagen-coated surface (taken as control for the study). Thereafter, the cells
      were encapsulated in CLECM hydrogels for 3D culture. In CLECM hydrogels, HepG2
      cells showed highly differentiated and polarized phenotype with the appearance of
      bile canaliculi-like structures and enhanced expression of mature hepatocyte
      markers. We further showed that CLECM hydrogels also supported the development of
      microvasculature in vitro, thus making it a suitable candidate for development of
      a prevascularized liver tissue construct. In conclusion, we proved the
      superiority of CLECM over collagen for 2D/3D human hepatocyte and endothelial
      cell culture. CLECM could serve as an efficient biomaterial platform in the
      development of a liver tissue construct for application in tissue engineering.

PMID- 29052368
TI  - Time course study of long-term biocompatibility and foreign body reaction to
      intraneural polyimide-based implants.
AB  - The foreign body reaction (FBR) against an implanted device is characterized by
      the formation of a fibrotic tissue around the implant. In the case of interfaces
      for peripheral nerves, used to stimulate specific group of axons and to record
      different nerve signals, the FBR induces a matrix deposition around the implant
      creating a physical separation between nerve fibers and the interface that may
      reduce its functionality over time. In order to understand how the FBR to
      intraneural interfaces evolves, polyimide non-functional devices were implanted
      in rat peripheral nerve. Functional tests (electrophysiological, pain and
      locomotion) and histological evaluation demonstrated that implanted devices did
      not cause any alteration in nerve function, in myelinated axons or in nerve
      architecture. The inflammatory response due to the surgical implantation
      decreased after 2 weeks. In contrast, inflammation was higher and more prolonged
      in the device implanted nerves with a peak after 2 weeks. With regard to tissue
      deposition, a tissue capsule appeared soon around the devices, acquiring maximal
      thickness at 2 weeks and being remodeled subsequently. Immunohistochemical
      analysis revealed two different cell types implicated in the FBR in the nerve:
      macrophages as the first cells in contact with the interface and fibroblasts that
      appear later at the edge of the capsule. Our results describe how the FBR against
      a polyimide implant in the peripheral nerve occurs and which are the main
      cellular players. Increasing knowledge of these responses will help to improve
      strategies to decrease the FBR against intraneural implants and to extend their
      usability. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 746
      757, 2018.

PMID- 29052369
TI  - Protein/polysaccharide-based scaffolds mimicking native extracellular matrix for
      cardiac tissue engineering applications.
AB  - Tissue engineering has emerged as a viable approach to treat disease or repair
      damage in tissues and organs. One of the key elements for the success of tissue
      engineering is the use of a scaffold serving as artificial extracellular matrix
      (ECM). The ECM hosts the cells and improves their survival, proliferation, and
      differentiation, enabling the formation of new tissue. Here, we propose the
      development of a class of protein/polysaccharide-based porous scaffolds for use
      as ECM substitutes in cardiac tissue engineering. Scaffolds based on blends of a
      protein component, collagen or gelatin, with a polysaccharide component,
      alginate, were produced by freeze-drying and subsequent ionic and chemical
      crosslinking. Their morphological, physicochemical, and mechanical properties
      were determined and compared with those of natural porcine myocardium. We
      demonstrated that our scaffolds possessed highly porous and interconnected
      structures, and the chemical homogeneity of the natural ECM was well reproduced
      in both types of scaffolds. Furthermore, the alginate/gelatin (AG) scaffolds
      better mimicked the native tissue in terms of interactions between components and
      protein secondary structure, and in terms of swelling behavior. The AG scaffolds
      also showed superior mechanical properties for the desired application and
      supported better adhesion, growth, and differentiation of myoblasts under static
      conditions. The AG scaffolds were subsequently used for culturing neonatal rat
      cardiomyocytes, where high viability of the resulting cardiac constructs was
      observed under dynamic flow culture in a microfluidic bioreactor. We therefore
      propose our protein/polysaccharide scaffolds as a viable ECM substitute for
      applications in cardiac tissue engineering. (c) 2017 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 769-781, 2018.

PMID- 29052370
TI  - Imidazolium- and Triazine-Based Porous Organic Polymers for Heterogeneous
      Catalytic Conversion of CO2 into Cyclic Carbonates.
AB  - CO2 adsorption and concomitant catalytic conversion into useful chemicals are
      promising approaches to alleviate the energy crisis and effects of global
      warming. This is highly desirable for developing new types of heterogeneous
      catalytic materials containing CO2 -philic groups and catalytic active sites for
      CO2 chemical transformation. Here, we present an imidazolium- and triazine-based
      porous organic polymer with counter chloride anion (IT-POP-1). The porosity and
      CO2 affinity of IT-POP-1 may be modulated at the molecular level through a facile
      anion-exchange strategy. Compared with the post-modified polymers with iodide and
      hexafluorophosphate anions, IT-POP-1 possesses the highest surface area and the
      best CO2 uptake capacity with excellent adsorption selectivity over N2 . The
      roles of the task-specific components such as triazine, imidazolium, hydroxyl,
      and counter anions in CO2 absorption and catalytic performance were illustrated.
      IT-POP-1 exhibits the highest catalytic activity and excellent recyclability in
      solvent- and additive-free cycloaddition reaction of CO2 with epoxides.

PMID- 29052371
TI  - Recyclable and Intrinsically Anti-cyanobacterial Polyanionic Membranes.
AB  - Cyanobacteria blooms possess serious threats to water resources. Herein, we
      report the synthesis of polyanionic membranes (PA-M) by in situ photo
      crosslinking of a sulfate-based anionic monomer followed by cation-exchange with
      metal cations, Fe3+ (PA-Fe), Cu2+ (PA-Cu), or Zn2+ (PA-Zn). The effect of cations
      on the anti-cyanobacterial activities against both Microcystis aeruginosa (M.
      aeruginosa) and Anabaena flos-aquae (A. flos-aquae) was investigated. All the
      prepared metal-containing membranes (PA-Fe, PA-Cu, PA-Zn) exhibit high anti
      cyanobacterial activities and long-term anti-cyanobacterial stability,
      demonstrating that the synthesized PA-M membranes can be used as an effective and
      safe inhibitor to control cyanobacterial blooms.

PMID- 29052372
TI  - Two-layer heterogeneous breast phantom for photoacoustic imaging.
AB  - Photoacoustic tomography (PAT) is emerging as a potentially important aid for
      breast cancer detection. Well-validated tissue-simulating phantoms are needed for
      objective, quantitative, and physically realistic testing for system development.
      Prior reported PAT phantoms with homogenous structures do not incorporate the
      irregular layered structure of breast tissue. To assess the impact of this
      simplification, we design and construct two-layer breast phantoms incorporating
      vessel-simulating inclusions and realistic undulations at the fat/fibroglandular
      tissue interface. The phantoms are composed of custom poly(vinyl chloride)
      plastisol formulations mimicking the acoustic properties of two breast tissue
      types and tissue-relevant similar optical properties. Resulting PAT images
      demonstrate that in tissue with acoustic heterogeneity, lateral size of imaging
      targets is sensitive to the choice of sound speed in image reconstruction. The
      undulating boundary can further degrade a target's lateral size due to sound
      speed variation in tissue and refraction of sound waves at the interface. The
      extent of this degradation is also influenced by the geometric relationship
      between an absorber and the boundary. Results indicate that homogeneous phantom
      matrixes may underestimate the degradation of PAT image quality in breast tissue,
      whereas heterogeneous phantoms can provide more realistic testing through
      improved reproduction of spatial variations in physical properties.

PMID- 29052373
TI  - Tissue multifractality and hidden Markov model based integrated framework for
      optimum precancer detection.
AB  - We report the application of a hidden Markov model (HMM) on multifractal tissue
      optical properties derived via the Born approximation-based inverse light
      scattering method for effective discrimination of precancerous human cervical
      tissue sites from the normal ones. Two global fractal parameters, generalized
      Hurst exponent and the corresponding singularity spectrum width, computed by
      multifractal detrended fluctuation analysis (MFDFA), are used here as potential
      biomarkers. We develop a methodology that makes use of these multifractal
      parameters by integrating with different statistical classifiers like the HMM and
      support vector machine (SVM). It is shown that the MFDFA-HMM integrated model
      achieves significantly better discrimination between normal and different grades
      of cancer as compared to the MFDFA-SVM integrated model.

PMID- 29052374
TI  - Portable fluorescence lifetime spectroscopy system for in-situ interrogation of
      biological tissues.
AB  - Fluorescence spectroscopy and lifetime techniques are potential methods for
      optical diagnosis and characterization of biological tissues with an in-situ,
      fast, and noninvasive interrogation. Several diseases may be diagnosed due to
      differences in the fluorescence spectra of targeted fluorophores, when, these
      spectra are similar, considering steady-state fluorescence, others may be
      detected by monitoring their fluorescence lifetime. Despite this complementarity,
      most of the current fluorescence lifetime systems are not robust and portable,
      and not being feasible for clinical applications. We describe the assembly of a
      fluorescence lifetime spectroscopy system in a suitcase, its characterization,
      and validation with clinical measurements of skin lesions. The assembled system
      is all encased and robust, maintaining its mechanical, electrical, and optical
      stability during transportation, and is feasible for clinical measurements. The
      instrument response function measured was about 300 ps, and the system is
      properly calibrated. At the clinical study, the system showed to be reliable, and
      the achieved spectroscopy results support its potential use as an auxiliary tool
      for skin diagnostics.

PMID- 29052375
TI  - [Referencing and inosculating--discussion on modern research strategy for
      ethnomedicines].
AB  - This article reviewed the current situation of ethnomedicines in China, and
      propos that the important research on ethnomedicine is to focus on the
      theoretical and empirical characteristics of ethnomedicine and the special
      features in the processes of collecting,processing and clinical application of
      ethnomedicine, which will be benefit to find the research principles and methods
      with the characteristics of ethnomedicine. These principles include making clear
      of the effective substances and mechanisms, and theoretical and empirical
      characteristics of ethnomedicine. The three methods in the new drug discovery
      technology system for ethnomedicine are to solve the difference in varieties of
      traditional medical systems depending on finding the similarities of them, to
      find the conjunction in varieties of traditional medical systems through the key
      herbs, and to find medicinal sources in varieties of traditional medical systems
      according to pharmaphylogeny.

PMID- 29052376
TI  - [The present situation and countermeasures of Uighur medicine compound].
AB  - Uighur medicine compound, which created and used by Uighur nationality, is under
      the guidance of the Uighur medical theory system of herbal formula and
      dialectical use of minority nationality conventional medicines. In recent years,
      Uighur medicine attracted more and more attention of people which have used and
      were using it. Combining the history of Uighur medicine, this article summarizes
      the Uighur resources, medicinal materials, drugs preparation, ancient documents,
      and the establishment of the clinical evaluation system and so on, and then
      analyzes the status quo and the existing problems in Uighur medicine compound
      research and industry. On this basis, we put forward countermeasures and
      suggestions for the development of Uighur medicine.

PMID- 29052377
TI  - [Two new triterpenoid acids from Uighur medicine Fomes officinalis].
AB  - Two new lanostane triterpenoid acids, 12beta, 15alpha-dihydroxy-24-methyl-3,23
      dioxo-lanosta-7,9(11)-dien-26-oic acid (1), and 3alpha, 12beta-dihydroxy-24
      methyl-7,23-dioxo-lanosta-8-en-26-oic acid (2), were isolated from the methanolic
      extract of Uighur medicine Fomes officinalis. Their structures were elucidated
      based on the analysis of spectroscopic data (1D, 2D NMR and HR-MS). Anti
      inflammatory and cytotoxicity assays revealed that both compound 1 and 2 show no
      inhibitory effects on nitric oxide production in lipopolysaccharide-induced
      RAW264.7 cells, and no cytotoxicity activities against HepG2 cells.

PMID- 29052378
TI  - [A new lignan from stem bark of Syringa pinnatifolia].
AB  - One new lignan, named Z-pinnatifolin A, along with ten known analogues, were
      isolated from the stem bark of Syringa pinnatifolia by various chromatographic
      methods. Their structures were extensively determined on basis of MS and NMR
      spectroscopic data analyses, and comparison with those in literature. Among them,
      compounds 3,4, and 8-11 were isolated from this genus for the first time, and 5-7
      were isolated from the specie for the first time. Compound 1 showed a moderate
      inhibition on NO production in BV-2 cells. The present study provides a
      preliminary data for clarification of bioactive ingredients of S.pinnatifolia
      with anti-myocardial ischemic effect.

PMID- 29052379
TI  - [Simultaneous determination of ten major compounds including iridoid glycosides
      and phenolic acids in Pterocephalus hookeri by UPLC-PDA].
AB  - This study is to develop an UPLC-PDA method for determination of 10 major
      components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity
      UPLCR BEH C18(2.1 mm *100 mm,1.7 MUm), and the column temperature was at 30 C.
      The mobile phase consists of water containing 0.2% phosphoric acid (A) and
      acetonitrile (B) in gradient elution at a flow rate of 0.4 mL*min-1. The
      detection wave length was set at 237 and 325 nm, and the injection volume was 1
      MUL in the UPLC system. The linear range of 10 detected compounds were good
      (r>=0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the
      RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible,
      which can be used for the simultaneous determination of the content of ten major
      components in P. hookeri.

PMID- 29052380
TI  - [Action mechanism of total flavonoids of Hippophae rhamnoides in treatment of
      myocardial ischemia based on network pharmacology].
AB  - In this study, a network pharmacological screening method was adopted to further
      study the active ingredients and action mechanism of total flavonoids of
      Hippophae rhamnoides(TFH) for the treatment of myocardial ischemia. Firstly TCMSP
      database and PubChem database were searched, and then the data were combined with
      oral bioavailability and drug analysis to screen flavonoids of H.rhamnoides
      compounds. Then predictive analysis was conducted for the 7 screened compounds by
      ChemMapper server.The obtained potential targets were imported into MAS 3.0.
      Database, and KEGG database was also used for targets analysis and pathway
      analysis. Finally Cystoscope 3.3.0 software was used to draw "compounds-targets
      pathway" network diagram. Virtual experiments predicted 68 potential targets and
      60 signaling pathways, and 31 targets and 23 pathways of them were directly or
      indirectly associated with myocardial ischemia. The results showed that TFH
      played a synergistic rolemainly through the regulation of calcium signaling
      pathway, VEGF signaling pathway and gap junction signaling pathway, which was
      consistent with literature reports. These results indicated that it can enhance
      heart function, protect vascular endothelial cells, and fight against myocardial
      ischemia probably by regulating platelet aggregation, lipid metabolism,
      inflammation and other processes.

PMID- 29052381
TI  - [Pharmacodynamic mechanism of modified Ganlu Yaoyu San intreatment of rheumatoid
      arthritis based on MAPK signaling pathway].
AB  - According to the findings, modified Ganlu Yaoyu San has a good anti-inflammatory
      activity, and can significantly alleviate the degree of arthritis. Its
      therapeutic effect for rheumatoid arthritis may be related to the regulation of
      MAPK pathway of synovial cells. In the study, the rat adjuvant arthritis(AA)
      model was established to further investigate the pharmacodynamic mechanism for
      regulating MAPK pathway of synovial cells. Enzyme-linked immune assay was used to
      determine the serum TNF-alpha level of AA rats administered with drug for two
      weeks, synovial tissue protein kinases ERK1/2 and p38 content were determined by
      immunohistochemistry, synovial tissue JNK1, ERK1, p38 gene(mRNA) expression were
      detected with fluorescence quantitative PCR(RT-PCR) method. According to the
      results, after administration for two weeks, the levels of serum TNF-alpha of AA
      rat was significantly decreased(P<0.05). After administration for four weeks, the
      protein expressions of p38 and ERK1/2 in synovial tissue were reduced(P<0.05 or
      P<0.01), the gene expressions of JNK1, p38 and ERK1 in knee joint synovial tissue
      were reduced(P<0.05 or P<0.01). In conclusion, modified Ganlu Yaoyu San can
      effectively treat rheumatoid arthritis. Its mechanism might be related to the
      reduction of TNF-alpha levels in serum, protein expression of p38 and ERK1/2 in
      synovial tissue, and JNK1, p38 and ERK1 gene expressions, and regulation of MAPK
      pathway.

PMID- 29052382
TI  - [Research progresses and formulation development of natural anti-mildew agents
      based on Chinese herbal medicines].
AB  - Owing to the intrinsic factors and some extrinsic environmental conditions, many
      foods, agricultural products and Chinese materia medicas (CMMs), if not handled
      properly in the processes of growth, harvesting, processing and storage, can be
      easily contaminated by all kinds of molds to produce mycotoxins of serious
      toxicity, which will not only affect the quality, safety and effectiveness of
      CMMs, but also result in potential threatens to human and animal's health and
      life. Therefore, in recent decades, it has become the focus on how to prevent and
      control the foods, agricultural products and CMMs from being moldy and producing
      toxicity for scientific preservation. Many Chinese herbal medicines (CHMs)
      especially those with high content of volatile oils with strong antifungal
      activities have been applied for the scientific preservation of foods,
      agricultural products and CMMs. Based on these situations, natural anti-mildew
      agents have been further developed and made into some useful dosage forms, such
      as tablets, aerosol, liposomes and inclusion, which will not only greatly expand
      the application scope of CHMs to make the use of anti-mildew agents more
      convenient, but also achieve the sustained or controlled release of the
      antifungal effect for scientific preservation of foods, agricultural products and
      CMMs.

PMID- 29052383
TI  - [Toxicity of mineral Chinese medicines containing mercury element].
AB  - Mineral Chinese medicine is the distinctive part of the Chinese traditional
      medicine. The mineral Chinese medicines containing mercury elements such as
      cinnabaris, calomelas and hydrargyri oxydum rubrum are widely applied in the
      clinical conditions because of their efficacy of sedative, sterilization,
      removing necrotic tissue and promoting granulation. However, the rationality and
      security of clinical application are questioned because of the toxic effect
      caused by mercury compounds. This paper would summarize the efficacy of the
      mineral Chinese medicines containing mercury element, as well as their
      hepatotoxicity, nephrotoxicity, embryotoxicity, and neurotoxicity effect and
      mechanisms. Improper usage or high dose of the mineral Chinese medicines
      containing mercury element would cause acute hepatotoxicity. Cinnabaris,
      calomelas and hydrargyri oxydum rubrum may lead to chronic hepatotoxicity,
      nephrotoxicity, embryotoxicity and neurotoxicity when they were applied
      externally to the skin for long-term use. In addition to the accumulation of
      mercury elements in the tissues and organs, the species and forms of mercury
      compounds absorbed into the body in different ways, should be also studied in
      order to understand the toxicity of the mineral Chinese medicines containing
      mercury element. Meanwhile the dose and period of treatment shall be also
      considered in order to provide the references for rational and safe clinical
      application of the mineral Chinese medicines containing mercury element.

PMID- 29052384
TI  - [Research progress of serum pharmacochemistry of traditional Chinese medicine].
AB  - Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective
      method to rapidly screen the effective substances and reveal the compatibility
      law of compound by identification and analysis of constituents migrating to blood
      after oral administration. In the last two decades, it has been universally
      accepted and widely applied in the field. With the cross-fusion with other
      disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network
      pharmacology and systems biology, serum pharmacochemistry shows comprehensive
      superiority in explaining drug changes in vivo and in vitro, interactions between
      drugs, interactions between drug and body, which coincides with the complexity of
      TCM compatibility, multi-components, multi-targets and multi-mechanisms. Based on
      the references related with the serum pharmacochemistry from CNKI scholar and
      Pubmed in 2013-2016, the research results of serum pharmacochemistry were
      statistically analyzed, and the key technical problems during the study of serum
      pharmacochemistry, for example, preparation of test sample, selection of
      experimental animal, determination of drug delivery scheme, method and time of
      the adoption blood, preparation and pretreatment of blood sample, as well as
      analysis of constituents migrating to blood, and the solving ways were
      empirically introduced. In addition, the development and comprehensive
      application of serum pharmacochemistry in TCM were summarized in this paper,
      hoping to lay a foundation for the further application of this method in TCM
      research.

PMID- 29052385
TI  - [Research advances on baicalin and baicalein as potential therapeutic agents for
      fibrotic disease].
AB  - Tissue and organ fibrosis is the major cause for disability and death related to
      a variety of diseases worldwide. As specific therapies to halt, or even to
      reverse the existing tissue fibrosis are not yet available, it is of great
      significance to find new anti-fibrosis therapeutic agents. Tissue and organ
      fibrosis is a nonphysiological scarring process, associated with excessive
      deposition of extracellular matrix, and leads to impairment of organ function.
      Fibrotic lesions of all organs show similar histological abnormalities. In recent
      years, plenty of studies showed that Baicalin and baicalein had anti-fibrosis
      effects in different tissues or organs. In this paper, the effects and mechanisms
      of baicalin and baicalein on different organ fibrosis were reviewed. Baicalin and
      its aglycone baicalein had similarity in structural and pharmacological
      characteristics, with broad biotransformation effect within the body. The
      research suggested that baicalin and baicalein can suppress different tissue and
      organ fibrosis occurrence and development via various mechanisms, including down
      regulating expression of promote-fibrosis cytokines, inhibiting pro-fibrogenic
      signaling pathways, anti-inflammatory and anti-oxidant effects. Though baicalin
      and baicalein are promising anti-fibrosis agents, there is still a long way to go
      before being approved as specific anti-fibrotic drugs.

PMID- 29052386
TI  - [General situation and comprehensive utilization of medicinal fungi resources in
      Heilongjiang province].
AB  - In order to develop and utilize the macrofungi in Heilongjiang province, numerous
      literatures have been investigated to make a comprehensive analysis of the number
      of known species of fungi in Heilongjiang province. There exists a total of 546
      species of macrofungus in Heilongjiang province belonging to 53 families and 13
      orders of 6 classes and 2 subdivisions. And its application value is classified,
      summarized and reviewed. Three hundred and twenty kinds of edible fungi, 214
      species of fungi with medicinal value, medicinal value in the anti-cancer effects
      of 167 species of fungi, 141 wood rot fungi, 141 species of ectomycorrhizal
      fungi, 88 poisonous species, 67 macrofungus which are not clarified whether could
      be edible or toxic. It shows a broad prospects for development and utilization of
      macrofungus resources in Heilongjiang province.

PMID- 29052387
TI  - [Climate change impacts on yield of Cordyceps sinensis and research on yield
      prediction model of C. sinensis].
AB  - Cordyceps sinensis is a Chinese unique precious herbal material, its genuine
      producing areas covering Naqu, Changdu in Qinghai Tibet Plateau, Yushu in Qinghai
      province and other regions. In recent 10 years, C. sinensis resources is
      decreasing as a result of the blindly and excessively perennial dug. How to
      rationally protect, develop and utilize of the valuable resources of C. sinensis
      has been referred to an important field of research on C. sinensis. The
      ecological environment and climate change trend of Qinghai Tibet plateau happens
      prior to other regions, which means that the distribution and evolution of C.
      sinensis are more obvious and intense than those of the other populations. Based
      on RS (remote sensing)/GIS(geographic information system) technology, this paper
      utilized the relationship between the snowline elevation, the average
      temperature, precipitation and sunshine hours in harvest period (April and may)
      of C. sinensis and the actual production of C. sinensis to establish a weighted
      geometric mean model. The model's prediction accuracy can reach 82.16% at least
      in forecasting C. sinensis year yield in Naqu area in every early June. This
      study can provide basic datum and information for supporting the C. sinensis
      industry healthful, sustainable development.

PMID- 29052388
TI  - [Comparison of development condition of different Liriope spicata seedlings].
AB  - The study identified the main morphological index of the seedlings classification
      including seedling age,the root width and number of newborn buds and coarse
      roots, according to the local agricultural production techniques and assessment
      of Liriope spicata's growth and development condition. After carrying on K
      cluster analysis of the morphological, we separated the seedlings into two
      levels. The first level (I): the new talent with the root width exceeding two
      point five millimeters, the new born buds exceeding three, and with the coarse
      root exceeding one. The second level (II): the old talent with the root width
      below one millimeters, the newborn buds below two and without coarse root. The
      study surveyed the plants' growth index dynamics, as well as the yield and
      quality of the tuberous root. The experimental results suggested that the growth
      condition of seedling Iwas better, the yield of earthnut higher, the quality of
      earthnut more excellent. The study lied the foundation of L. spicata's grading
      standards and standardized production.

PMID- 29052389
TI  - [Research on periodical changes and metabolism relations of active components in
      Lonicera japonica leaves].
AB  - The study is aimed to explore the metabolism rule of Lonicera japonica by
      investigating the primary and secondary metabolism process in different growth
      periods. HPLC and other methods were used to measure metabolism indexes of leaves
      collected in last ten days of every month. The results suggested that the maximum
      (78.59%) and minimum (60.83%) of water content were found in March and December.
      The content of total sugar reached a high level from December to February and the
      maximum (275.8 mg*g-1) appeared in October, while it reduced significantly at
      other time. The change of chlorogenic acid, neochlorogenic acid, galuteolin,
      caffeic acid were basically consistent and the highest content of them
      synchronously appeared (42.79, 2.01, 7.13, 0.16 mg*g-1) in March. The content of
      primary and secondary metabolite in L. japonica leaves reached a high level from
      March to May, and the main related elements with effective components were K, Mg,
      P, aspartate, threonine, proline, valine, cysteine, isoleucine and phenylalanine.

PMID- 29052390
TI  - [Diversity of agronomic traits of Paris polyphylla var. chinensis and their
      correlation with rhizome yield and active compositions].
AB  - The supply deficiency of crude medicinal plant of Paris polyphylla var. chinensis
      has become a bottleneck for related medicinal industry. An important approach to
      increase herbal production is to breed high-yield cultivated variety, which
      characterized ideal plant morphology. In the present study, we collected 99 wild
      germplasm resources of P. polyphylla and then measured their 12 main agronomic
      traits and contents of polyphyllin VII,VI,II,I. Followed analyses were used to
      characterize those traits and explore the potential connection with herbal yield
      or quality. The results showed that: 1There was ample morphological diversity in
      wild P. polyphylla, whose variation of agronomic traits reduced according to
      followed order: content of polyphyllin, weight of dry rhizome, petiole length,
      stem length, petal length, pedicel length, sepal length, leaf width, leaf length,
      sepal width, leaf number, stamen number, petal number. 2 Most of those traits
      were significantly correlated to each other and generally represented the
      characterization of photosynthetic organs or reproductive organ. 3The total
      content of polyphyllin VII,VI,II,Ivaried between 0.02% and 0.87% and averagedat
      0.13%, which showed no significant correlation with any agronomic trait. 4Plant
      breeders should play more attention on those germplasm resources with large
      leaves, large sepals and high stem.

PMID- 29052391
TI  - [Research on bacteria microecology in root rot rhizosphere soil of Coptis
      chinensis produced in Shizhu city].
AB  - Illumina Hiseq 2500 high-throughput sequencing platform was used to study the
      bacteria richness and diversity, the soil enzyme activities, nutrients in
      unplanted soil, root-rot and healthy rhizophere soil of Coptis chinensis for
      deeply discussing the mechanism of the root-rot of C. chinensis. The high
      throughput sequencing result showed that the artificial cultivation effected the
      bacteria community richness and diversity. The bacteria community richness in
      healthy and diseased rhizosphere soil showed significant lower than that of in
      unplanted soil (P<0.05) and declined bacteria diversity. The bacteria community
      richness in root-rot rhizosphere soil increased significantly than that of health
      and unplanted soil and the diversity was lower significant than that of unplanted
      soil (P<0.05). The results of soil nutrients and enzyme activities detected that
      the pH value, available phosphorus and urease activity decreased and the sucrase
      activity increased significantly (P<0.05). The content of organic carbon and
      alkaline hydrolysis nitrogen the catalase and urease activity in root rot soil
      samples was significantly lower than that of healthy soil samples (P<0.05).
      However, the contents of available phosphorus and available potassium were
      significantly in root-rot sample higher than that of healthy soil samples
      (P<0.05). Comprehensive analysis showed that the artificial cultivation declined
      the bacteria community richness and diversity. The bacteria community richness
      decreased significantly and the decreased diversity may be the cause of the root
      rot. Meanwhile, the decrease of carbon and the catalase activity may be another
      cause of the root-rot in C. chinensis produced in Shizhu city, Chongqing
      province.

PMID- 29052392
TI  - [Cloning and protein expression analysis of monoterpene synthase gene TwMS in
      Tripterygium wilfordii].
AB  - In this study, we cloned a monoterpene synthases, TwMS from Tripterygium
      wilfordii suspension cells. TwMS gene contained a 1 797 bp open reading frame
      (ORF), encoding a polypeptide of 579 amino acids, which deduced isoelectric point
      (pI) was 6.10 and the calculated molecular weight was 69.75 kDa. Bioinformation
      analysis showed that the sequence of TwMS was consistent with the feature of
      monoterpene synthases. Differential expression analysis revealed that the
      relative expression level of TwMS increased significantly after being induced by
      methyl jasmonate (MeJA). The highest expression level occurred at 24 h. TwMS
      protein was successfully expressed in Escherichia coli BL21 (DE3), which laid the
      foundation for identifying the function of T. wilfordii monoterpene synthases.

PMID- 29052393
TI  - [Identification of Panax ginseng, P. notoginseng and P. quinquefolius admixture
      by multiplex allele-specific polymerase chain reaction].
AB  - To achieve a molecular method to identify Panax ginseng, P. notoginseng,P.
      quinquefolius and their admixture. The ITS,18S and matK sequences of Panax genus
      were analyzed to develop species-specific SNP marker. Three pairs of species
      specific primers were designed to establish a multiplex allele-specific
      polymerase chain reaction (MAS-PCR) and the samples from different region were
      tested. The results showed that when the annealing temperature was 60 C and the
      cycle number was 35, approximately 250, 500,1 000 bp specific band were obtained
      from P. ginseng, P. notoginseng and P. quinquefolius obtain, respectively. This
      method could also be used to authentificate admixture samples and could detect
      0.5% percent of P. notoginseng or P. quinquefolius adulterated in P. ginseng, or
      0.5% percent of P. ginseng or P. quinquefolius adulterated in P. notoginseng. The
      detect limit of P. ginseng in P. quinquefolius was 0.5% and P. notoginseng in P.
      quinquefolius was 1%. This results showed that the present method could be used
      as a promise method to identify Panax ginseng, P. notoginseng, P. quinquefolius
      and their admixture.

PMID- 29052394
TI  - [Application of random forest algorithm in fingerprint of Chinese medicine:
      different brands of Xiasangju granules as example].
AB  - To establish a random forest algorithm for identifying and classifying different
      brands of Xiasangju granules, and provide effective reference for identifying
      multi-index complex fingerprint. HPLC method was used to collect the fingerprint
      of 83 batches of Xiasangju granules from different manufacturers. The
      classification of Xiasangju granules samples based on chromatographic
      fingerprints was identified by chemometric methods including principal component
      analysis (PCA), partial least squares discriminate analysis (PLS-DA) and random
      forest analysis (RF). The superiority of the above three chemometric methods was
      compared. The results showed that the fingerprints of 83 batches of Xiasangju
      granules were established in this study. PCA could only explicate 56.52% variance
      contribution rate and could not completely classify the samples; PLS-DA analysis
      was superior to PCA, explicating 63.43% variance contribution rate and could
      obtain certain separation; RF could well classify the samples into 3 types, and
      the predication accuracy of the proposed method was 96.5%. Therefore, The results
      indicate that RF combined with HPLC fingerprint could effectively construct
      traditional Chinese medicine quality control and analysis system.

PMID- 29052395
TI  - [Purifying process of gynostemma pentaphyllum saponins based on "adjoint marker"
      online control technology and identification of their compositions by UPLC-QTOF
      MS].
AB  - To optimize the purification process of gynostemma pentaphyllum saponins (GPS)
      based on "adjoint marker" online control technology with GPS as the testing
      index. UPLC-QTOF-MS technology was used for qualitative analysis. "Adjoint
      marker" online control results showed that the end point of load sample was that
      the UV absorbance of effluent liquid was equal to half of that of load sample
      solution, and the absorbance was basically stable when the end point was stable.
      In UPLC-QTOF-MS qualitative analysis, 16 saponins were identified from GPS,
      including 13 known gynostemma saponins and 3 new saponins. This optimized method
      was proved to be simple, scientific, reasonable, easy for online determination,
      real-time record, and can be better applied to the mass production and automation
      of production. The results of qualitative analysis indicated that the "adjoint
      marker" online control technology can well retain main efficacy components of
      medicinal materials, and provide analysis tools for the process control and
      quality traceability.

PMID- 29052396
TI  - [Effect of wintergreen oil on in vitro transdermal permeation of osthole and
      geniposide].
AB  - The aim of this study was to investigate the transdermal penetration enhancement
      effect of wintergreen oil and its action mechanisms. The in vitro transdermal
      tests were carried out to study the transdermal penetration enhancement effect of
      wintergreen oil by using osthole and geniposide as the lipophilic and hydriphilic
      model drugs. Fourier-transform infrared spectroscopy was used to investigate the
      effect of wintergreen oil on the molecular structure of rat stratum corneum, and
      the scanning electron microscope was employed to observe the change of rat skin
      surface after treatment by the oil. The wintergreen oil at proper concentrations
      could effectively promote the transdermal permeation of osthole and geniposide,
      and exhibited better penetration-enhancing activity for the lipophilic osthole,
      close to the commonly used classical penetration enhancer azone. The infrared
      spectroscopy study and scanning electron microscope showed that wintergreen oil
      mainly acted on the stratum corneum lipids, reduced dense stratum corneum, and
      reduced the skin barrier function. Thus, the wintergreen oil could effectively
      facilitate the transdermal absorption of the lipophilic and hydrophilic drugs,
      resulting from the lowed skin barrier function.

PMID- 29052397
TI  - [Effect of processing time of Polygoni Multiflori Radix on content changes of 16
      componens].
AB  - To study 48 h processing time of Polygoni Multiflori Radix on its contents and
      changes of chemical components. HPLC was used to determine the contents of
      various components in 22 Polygoni Multiflori Radix samples with different
      processing time, and then the fingerprint similarity analysis and clustering
      analysis were used for characteristics analysis. Results showed that the
      similarity was between 0.9-1.0, with good correlation between the samples. In the
      clustering analysis, the 22 Polygoni Multiflori Radix and processed Polygoni
      Multiflori Radix samples were classified into 4 types according to the
      composition changes. The results demonstrated that 4-5 h was the best processing
      time, providing references for quality control and further study of Polygoni
      Multiflori Radix.

PMID- 29052398
TI  - [Protective effect and mechanism of scutellarin ethyl ester on focal cerebral
      ischemia induced by ligation of middle cerebral artery in rats].
AB  - To observe the protective effect of scutellarin ethyl ester on focal cerebral
      ischemia injury induced by middle cerebral artery occlusion in rats(MCAOR), and
      explore its mechanism. Totally 84 male SD rats were randomly divided into seven
      groups: sham-operated group, model group,positive drug group(niomdipine,12 mg*kg
      1), Brevisapin tablets group(48 mg*kg-1), and high, middle and low-dose
      scutellarin ethyl ester groups(100, 50, 25 mg*kg-1). The MCAOR model was prepared
      by using thread embolism method to observe the neurological function of rats, the
      area of cerebral infarction was measured with TTC, and the levels of MDA, SOD and
      NO in serum were detected with semiautomatic biochemistry analyzer.Ox-LDL and TNF
      alpha cell injury models was established by treating HUVECs with 200 mg*L-1 ox
      LDL and 100 MUg*L-1 TNF-alpha,and the levels of MDA, SOD, NO, ET, 6-keto
      PGF1alpha,TXB2, IL-1, IL-6, IL-8, ICAM-1 and PECAM-1 in the cell supernatant were
      determined. The results showed that scutellarin ethyl ester could effectively
      improve the neurological function of MCAOR rats, and significantly reduce the
      area of cerebral infarction. Compared with the model group, activities of SOD and
      NO in serum increased, while content of MDA decreased. In the cell supernatant,
      activities of SOD, 6-keto-PGF1alpha and NO increased, content of IL-1, IL-6, IL
      8, ICAM-1, PECAM-1, TXB2, ET and MDA decreased, which indicated that scutellarin
      ethyl ester has a certain protective effect on focal cerebral ischemia injury
      induced by middle cerebral artery occlusion in rats, and its mechanism may be
      related to antioxidative stress, improvement of endothelial function and
      reduction in inflammatory reaction.

PMID- 29052399
TI  - [Effect of total flavonoids in Scutellaria barbata in mediating autophagy in
      tumor cells via PI3K/AKT/mTOR pathway].
AB  - To investigate the effect of the total flavonoids in Scutellaria barbata(TF-SB)
      against autophagy in tumor cells in vivo, and further determine whether the
      mechanism is correlated with the PI3K/AKT/mTOR pathway, which lead to autophagy
      induced tumor cell death. Melanoma-bearing mice were prepared and divided into
      control group, rapamycin group (Rap 1.5 mg*kg-1), and high, middle and low-dose
      TF-SB (200, 100, 50 mg*kg-1) groups. The groups were given drugs once a day for
      successively 11 days. The inhibitory effect of TF-SB on the growth of melanoma
      was determined by measuring tumor volume and tumor inhibition rate. TUNEL method
      was used to detect the apoptosis of tumor cells to further verify the antitumor
      activity of TF-SB. The protein expressions of LC3-I and LC3-II were detected by
      Western blot, and the relative expression of LC3-II was calculated based on LC3
      II/LC3-I. In addition, the effect of TF-SB on autophagy of tumor cells, the
      underlying molecular mechanism of TF-SB in inducing autophagy and PI3K/AKT/mTOR
      pathway marker protein phosphorylation were also studied. According to the
      results, TF-SB effectively inhibited melanoma growth in mice, reduced tumor
      volume, increased the tumor inhibition rate, and significantly increased tumor
      cell apoptosis index and the ratio of LC3-II/LC3-I (P<0.05, P<0.01 or P<0.001).
      The protein expressions of p-PI3K, p-AKT and p-mTOR were also suppressed
      dramatically compared with those in control group (P<0.05, P<0.01 or P<0.001). In
      conclusion, the total flavonoids in S. barbata could inhibit the growth of
      melanoma in vivo by inducing autophagy and apoptosis of tumor cells, which may be
      correlated with suppression of PI3K/AKT/mTOR pathway.

PMID- 29052400
TI  - [Protective effect of ginsenoside Rb1 on doxorubicin-induced myocardial
      autophagy].
AB  - Ginsenoside Rb1 (Rb1), which is one of the main ingredients derived from Panax
      ginseng, has been found to have extensive pharmacological activities including
      antioxidant, anti-inflammatory, anticancer properties. In this study, the effect
      of Rb1 on doxorubicin-induced myocardial autophagy was studied with H9c2 as the
      study object. CCK-8 method, transmission electron microscope observation,
      fluorescence staining observation and Western blot were used to detect changes in
      H9c2 cell proliferation and autophagy after treatment. According to the results,
      doxorubicin could cause cell viability decrease, significant increase in the LC3
      II/LC3-I ratio and down-regulation of the expression of p62. Pretreatment with
      ginsenoside Rb1 inhibited cell viability decrease and increase in doxorubicin
      induced autophagic structure and LC3-II/LC3-I ratio, and down-regulation of the
      expression of p62. In conclusion, doxorubicin could induce H9c2 cell death and
      induce autophagy, and ginsenoside Rb1 showed a protective effect on DOX-induced
      cardiotoxicity, which may be correlated with suppression of DOX-induced
      autophagy.

PMID- 29052401
TI  - [Relaxation effect of buddleoside combined with luteolin on isolated vessels in
      vivo and its mechanism].
AB  - To study the relaxation effect of buddleoside combined with luteolin on aortic
      rings in SD rats and its mechanism. The effect of buddleoside alone(7.5*10-6g*mL
      1), luteolin alone(7.5*10-6g*mL-1) and the combination of buddleoside and
      luteolin(1?4) on norepinephrine-induced contractility of complete, endothelium
      denuded, and L-NAME and indomethacin-pretreated thoracic aorta in SD rats were
      observed in the in vitro ring tension test. Western blot was used to detect p-Akt
      and p-eNOS protein expressions in the thoracic aorta. The experimental results
      showed that buddleoside combined with luteolin could significantly increase the
      relaxation rate of blood vessels and endothelium and L-NAME-pretreated vascular
      rings compared with the two single administrations. And buddleoside combined with
      luteolin could also significantly increase p-Akt and p-eNOS protein
      expressions.The results suggested that the combination of buddleoside and
      luteolin could effectively relax the blood vessel, and the mechanism may be to
      increase the synthesis and release of NO and reach the role of relaxing blood
      vessel by activating PI3K/Akt/NO signaling pathway and enhancing the activity of
      eNOS.

PMID- 29052402
TI  - [Effect of Qibai Pingfei capsule medicated serum on protein expressions of KATP
      channel in pulmonary arterial smooth muscle cells via nitric oxide].
AB  - To investigate the ATP-sensitive potassium channel (KATP channel) protein
      expressions during different periods under hypoxia condition and explore the
      effect of Qibai Pingfei capsule medicated serum (hereinafter referred to as QBPF)
      on the correlation between the protein expressions of KATP channel and nitric
      oxide in rat pulmonary arterial smooth muscle cells(PASMCs). Qibai Pingfei
      capsules were given to SD rats via continuous gavage for 10 days to obtain QBPF.
      Primary rats PASMCs were cultured by the direct adherent culture method. Western
      blot was applied to detect the protein expression levels of KATP channel (Kir6.1
      and SUR2B) in PASMCs. Then the noncompetitive inhibitor of NO synthase--Nomega
      nitro-L-arginine methyl ester(L-NAME) and KATP channel inhibitor--glyburide(GLYB)
      were applied respectively to evaluate the effect of QBPF on the protein
      expressions of KATP channel. The protein expressions of Kir6.1 and SUR2B were
      increased after 6-hour hypoxia treament, peaked at the 24-hour hypoxia treament,
      and decreased in both 48-hour and 72-hour hypoxia groups. Especially, QBPF could
      further up-regulate the Kir6.1 and SUR2B protein expressions under 24-hour
      hypoxia condition; however, such up-regulation effect could be blocked by KATP
      channel inhibitor GLYB and NO specific inhibitor L-NAME, indicating that QBPF
      played the role of opening KATP channel. The regulatory mechanism was probably
      associated with up-regulating KATP channel protein expression via NO relative
      pathway, involving pulmonary vasodilation, and thus relieving the occurence and
      development of COPD.

PMID- 29052403
TI  - [Serum metabonomics in mice infected with mycoplasma pneumoniae by UPLC-Q-TOF
      MS].
AB  - Ultra high performance liquid chromatography coupled with tandem quadrupole time
      of flight mass spectrometry(UPLC-Q-TOF-MS) was applied to metabonomics study in
      BALB/c mice infected with mycoplasma pneumoniae(MP) to analyze the changes in
      serum endogenous metabolites, identify potential biomarkers associated with
      mycoplasma pneumoniae pneumonia(MPP), analyze the metabolic pathway and explore
      the pathogenic mechanism of MPP. The BALB/c mice were inoculated with MP by
      repeated intranasal infectious routes to establish MPP models, and the results of
      the lung tissue biopsy, IgM and mycoplasma nucleic acid content determination
      showed that the models of MP in BALB/c mice were successfully established. UPLC-Q
      TOF-MS was used to analyze the serum metabolic profiling of BALB/c mice infected
      with MP, and then principal component analysis(PCA) was combined with orthogonal
      partial least squares discriminant analysis(OPLS-DA) for data processing. The
      results showed that there were significant differences in serum metabolic profile
      between the MP infected mice and the normal mice. Forty-seven potential
      biomarkers such as ornithine, cortisol, vitamin A and tryptophan were screened
      out by database searching and MS information matching. These potential biomarkers
      related to 17 metabolic pathways including retinol metabolism, arginine and
      proline metabolism, steroid hormone synthesis and so on. The metabonomic research
      method for serum of mice infected with mycoplasma pneumoniae based on UPLC-Q-TOF
      MS was established in this study. The metabolic changes of endogenous small
      molecules in mice infected with MP were reflected in the overall level, laying
      the foundation for the selection and evaluation of MPP drugs.

PMID- 29052404
TI  - [Clinical efficacy and mechanism of total glucosides from white paeony for
      radioactive liver damage].
AB  - To discuss the effects of total glucosides from white paeony on preventing and
      treating radioactive liver damage, and explore its possible mechanisms. Thirty
      six patients with primary hepatic carcinoma from 105th Hospital of Chinese PLA
      were treated with 3-dimensional conformal radiotherapy and randomly divided into
      simple irradiation group, total glucosides from white paeony group, and control
      group. The levels of AST, ALT, HA, LN, PCIII, CIV and TGF-beta1 in serum of
      various groups were determined by using ELISA method. As compared with the simple
      irradiation group and control group, total glucosides from white paeony could
      obviously decrease the levels of AST, ALT, HA, LN, PCIII, CIV and TGF
      beta1(P<0.05, P<0.01). The results showed that the total glucosides from white
      paeony could effectively prevent and treat radioactive liver damage, and its
      mechanism might be associated with decreasing the levels of TGF-beta1, and
      inhibiting the synthesis of collagen synthesis.

PMID- 29052405
TI  - [ITS2 sequence analysis and identification of medicinal Artemisia plants].
AB  - Artemisia hedinii occupies an important position in the Tibetan medicine. Plants
      in Artemisia vary a lot and are widely distributed in the Qinghai-Tibet Plateau,
      many plants in Artemisia look similar, making traditional identification methods
      laborious. In this article, ITS2 sequences were used as DNA barcoding to identify
      four kinds of confusable Tibetan medicine plants in Artemisia, aiming to
      establish a rapid and accurate identification methods. Twenty-one samples in
      Artemisia were collected from the Qinghai-Tibet Plateau, ITS2 sequence PCR
      amplification and sequencing were conducted after the extraction of DNA. Another
      11 sequence downloaded from Genbank were added to the analysis. Genetic distance
      calculation and analysis, building Neighbor Joining (NJ) phylogenetic tree were
      conducted by MEGA 6.0, also comparison of secondary structures of ITS2 sequences
      among samples. A. hedinii, A. annua, A. dubia and A. argyi shared close genetic
      distance, but the maximum distance between the four species was much greater than
      the minimum distance within each species, NJ tree showed that the four species
      went to four separate branches, differences among secondary structures of ITS2
      sequences also made it clear to identify these medical plants. It could be an
      accurate and rapid method for identification and recognition, as well as the
      evolutionary relationships between the species by using ITS2 sequence as DNA
      barcode for plants of Tibetan Artemisia. The study provides theoretical basis for
      quality control, medication safety and rational exploitation.

PMID- 29052406
TI  - [Status and suggestions for adjuvant standard for Chinese materia medica
      processing in China].
AB  - In this paper, the status of adjuvant standard for Chinese materia medica
      processing in the Chinese Pharmacopoeia 2015 edition, the National Specification
      of Chinese Materia Medica Processing, and the 29 provincial specification of
      Chinese materia medica was summarized, and the the status including general
      requirements, specific requirements, and quality standard in the three grade
      official specifications was collected and analyzed according to the "medicine
      adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper
      also introduced the research situation of adjuvant standard for Chinese materia
      medica processing in China; In addition, analyzed and discussed the problems
      existing in the standard system of adjuvant for Chinese materia medica
      processing, such as lack of general requirements, low level of standard,
      inconsistent standard references, and lack of research on the standard, and
      provided suggestions for the further establishment of the national standards
      system of adjuvant for Chinese materia medica processing.

PMID- 29052407
TI  - [Individualized clinical treatment from the prospective of hepatotoxicity of non
      toxic traditional Chinese medicine].
AB  - Traditional Chinese medicine has a long history in clinical application, and been
      proved to be safe and effective. In recent years, the toxicity and side-effects
      caused by the western medicine have been attracted much attention. As a result,
      increasing people have shifted their attention to traditional Chinese medicine.
      Nonetheless, due to the natural origin of traditional Chinese medicine and the
      lack of basic knowledge about them, many people mistakenly consider the absolute
      safety of traditional Chinese medicine, except for well-known toxic ones, such as
      arsenic. However, according to the clinical practices and recent studies, great
      importance shall be attached to the toxicity of non-toxic traditional Chinese
      medicine, in particular the hepatotoxicity. Relevant studies indicated that the
      toxicity of non-toxic traditional Chinese medicine is closely correlated with
      individual gene polymorphism and constitution. By discussing the causes and
      mechanisms of the hepatotoxicity induced by non-toxic traditional Chinese
      medicine in clinical practices, we wrote this article with the aim to provide new
      ideas for individualized clinical therapy of traditional Chinese medicine and
      give guidance for rational and safe use of traditional Chinese medicine.

PMID- 29052409
TI  - Recommended composition of influenza virus vaccines for use in the 2018 southern
      hemisphere influenza season.

PMID- 29052408
TI  - Indirect methods to estimate hidden population.
AB  - Estimating the prevalence of the so-called "hidden populations" can be
      challenging, because the identification of its members is difficult due to their
      socially sanctionable or illegal behaviours. This article provides a critical
      review of the most widely used methods for estimating the size of a hard-to-reach
      population. All are indirect methods, based on incomplete data sources. Depending
      on the available data, one method can be more appropriate than another. Besides,
      each method must fulfil a number of requirements, and each one may be subject to
      specific risk of bias. To choose the most suitable method, an accurate evaluation
      of the available data is necessary, and. if possible several methods should be
      used simultaneously to be able to compare the results and to critically evaluate
      if these results fit with the reality.

PMID- 29052410
TI  - Zoonotic influenza viruses: antigenic and genetic characteristics and development
      of candidate vaccine viruses for pandemic preparedness.

PMID- 29052411
TI  - Photoresponse Enhancement in Monolayer ReS2 Phototransistor Decorated with CdSe
      CdS-ZnS Quantum Dots.
AB  - ReS2 films are considered as a promising candidate for optoelectronic
      applications due to their direct band gap character and optical/electrical
      anisotropy. However, the direct band gap in a narrow spectrum and the low
      absorption of atomically thin flakes weaken the prospect for light-harvesting
      applications. Here, we developed an efficient approach to enhance the performance
      of a ReS2-based phototransistor by coupling CdSe-CdS-ZnS core-shell quantum dots.
      Under 589 nm laser irradiation, the responsivity of the ReS2 phototransistor
      decorated with quantum dots could be enhanced by more than 25 times (up to ~654
      A/W) and the rising and recovery time can be also reduced to 3.2 and 2.8 s,
      respectively. The excellent optoelectronic performance is originated from the
      coupling effect of quantum dots light absorber and cross-linker ligands 1,2
      ethanedithiol. Photoexcited electron-hole pairs in quantum dots can separate and
      transfer efficiently due to the type-II band alignment and charge exchange
      process at the interface. Our work shows that the simple hybrid zero- and two
      dimensional hybrid system can be employed for photodetection applications.

PMID- 29052412
TI  - Co(II)-Doped Cd-MOF as an Efficient Water Oxidation Catalyst: Doubly
      Interpenetrated Boron Nitride Network with the Encapsulation of Free Ligand
      Containing Pyridine Moieties.
AB  - Development of an efficient and inexpensive water oxidation electrocatalyst using
      the earth-abundant elements is still far to go. Herein, a novel strategy has been
      demonstrated for developing the OER electrocatalyst by doping Co(II) in to a
      three-dimensional Cd-based MOF that contains a naked pyridine moieties in the
      form of uncoordinated ligand. Electrochemically active CoCd-MOF was resulted
      through the doping of Co(II) into the inactive Cd-MOF. CoCd-MOF exhibited very
      high catalytic activity in water oxidation reaction. An overpotential of 353 mV
      is required to produce an anodic current density of 1 mA/cm2 under alkaline
      conditions. Further, the CoCd-MOF exhibits remarkable recyclability over 1000
      cycles.

PMID- 29052413
TI  - Asymmetric Synthesis of Functionalized trans-Cyclopropoxy Building Block for
      Grazoprevir.
AB  - A practical and asymmetric synthesis of a functionalized trans-cyclopropoxy
      building block for the preparation of the HCV NS3/4a protease inhibitor
      grazoprevir is reported. Intramolecular SN2 displacement-ring closure, followed
      by a Baeyer-Villiger oxidation, yields the desired trans-cyclopropanol with full
      control of diastereoselectivity. A terminal alkyne is then effectively installed
      using LiNH(CH2)2NEt2. Starting from (S)-epichlorohydrin, the cyclopropoxy
      building block is prepared in 51% overall yield with >99.8% optical purity
      without isolation of any intermediates.

PMID- 29052414
TI  - Momentum Distribution of Electrons Emitted from Resonantly Excited Individual
      Gold Nanorods.
AB  - Electron emission by femtosecond laser pulses from individual Au nanorods is
      studied with a time-of-flight momentum resolving photoemission electron
      microscope (ToF k-PEEM). The Au nanorods adhere to a transparent indium-tin oxide
      substrate, allowing for illumination from the rear side at normal incidence.
      Localized plasmon polaritons are resonantly excited at 800 nm with 100 fs long
      pulses. The momentum distribution of emitted electrons reveals two distinct
      emission mechanisms: a coherent multiphoton photoemission process from the
      optically heated electron gas leads to an isotropic emission distribution. In
      contrast, an additional emission process resulting from the optical field
      enhancement at both ends of the nanorod leads to a strongly directional emission
      parallel to the nanorod's long axis. The relative intensity of both contributions
      can be controlled by the peak intensity of the incident light.

PMID- 29052415
TI  - Activity of Escherichia coli, Aspergillus niger, and Rye Phytase toward Partially
      Phosphorylated myo-Inositol Phosphates.
AB  - Kinetic parameters for the dephosphorylation of sodium phytate and a series of
      partially phosphorylated myo-inositol phosphates were determined at pH 3.0 and pH
      5.0 for three phytase preparations (Aspergillus niger, Escherichia coli, rye).
      The enzymes showed lower affinity and turnover numbers at pH 3 compared to pH 5
      toward all myo-inositol phosphates included in the study. The number and
      distribution of phosphate groups on the myo-inositol ring affected the kinetic
      parameters. Representatives of the individual phytate dephosphorylation pathways
      were identified as the best substrates of the phytases. Within the individual
      phytate dephosphorylation pathways, the pentakisphosphates were better substrates
      compared to the tetrakisphosphates or phytate itself. E. coli and rye phytase
      showed comparable activities at both pH values toward the tetrakis- and
      trisphosphate, whereas A. niger phytase exhibited a higher activity toward the
      tetrakisphosphate. A myo-inositol phosphate with alternate phosphate groups was
      shown to be not significantly dephosphorylated by the phytases.

PMID- 29052416
TI  - N-Heterocycle-Forming Amino/Carboperfluoroalkylations of Aminoalkenes by Using
      Perfluoro Acid Anhydrides: Mechanistic Studies and Applications Directed Toward
      Perfluoroalkylated Compound Libraries.
AB  - This work describes a practical and efficient method for synthesizing a diverse
      array of perfluoroalkylated amines, including N-heterocycles, to afford
      perfluoroalkylated chemical libraries as potential sources of drug candidates,
      agrochemicals, and probe molecules for chemical-biology research. Perfluoro acid
      anhydrides, which are commonly used in organic synthesis, were employed as a
      perfluoroalkyl source for intramolecular amino- and carbo-perfluoroalkylations of
      aminoalkenes, affording perfluoroalkylated N-heterocycles, including: aziridines,
      pyrrolidines, benzothiazinane dioxides, indolines, and hydroisoquinolinones.
      Diacyl peroxides were generated in situ from the perfluoro acid anhydrides with
      urea.H2O2, and allowed to react with aminoalkenes in the presence of copper
      catalyst to control the product selectivity between amino- and carbo
      perfluoroalkylations. To illustrate the synthetic utility of bench-stable
      trifluoromethylated aziridine, which was prepared on a gram scale, we used it to
      synthesize a wide variety of trifluoromethylated amines including complex
      molecules, such as trifluoromethylated tetrahydroharmine and spiroindolone. A
      mechanistic study of the role of the copper catalyst in the
      aminotrifluoromethylation of allylamine suggested that Cu(I) accelerates CF3
      radical formation via decomposition of diacyl peroxide, which appears to be the
      turnover-limiting step, while Cu(II) controls the product selectivity.

PMID- 29052417
TI  - Structure-Based Kinetic Control in a Domino Process: A Powerful Tool Toward
      Molecular Diversity in Chromone Series.
AB  - Two successive original routes leading to two novel families of polyheterocycles
      starting from the versatile chromone-based Michael acceptors platform are
      reported herein. The major aspect of this work is the selective access to these
      frameworks by changing the course of the domino process involved in their
      formation. First, enaminochromanones were selectively accessed under uncommon
      kinetic control. In this study, we showed that the tuning of the selectivity
      toward the kinetic product could be achieved by key structural modifications of
      the different reaction partners involved in the domino process. Once selectivity
      was efficiently controlled, enaminochromanones were ultimately transformed into a
      more complex family of polyheterocycles containing the pyrrolo-oxazinone
      framework. Here, the modulation of the domino sequence toward these particularly
      scarce structures was enabled by a pivotal switch in reactivity induced by aryl
      lambda3-iodanes.

PMID- 29052418
TI  - Formation of Ketenimines via the Palladium-Catalyzed Decarboxylative pi-Allylic
      Rearrangement of N-Alloc Ynamides.
AB  - A new approach for the formation of ketenimines via a decarboxylative allylic
      rearrangement pathway that does not require strong stabilizing or protecting
      groups has been developed. The products can be readily hydrolyzed into their
      corresponding secondary amides or reacted with sulfur ylides to perform an
      additional [2,3]-Wittig process. Mechanistic studies suggest an outer-sphere
      process in which reductive alkylation is rate-limiting.

PMID- 29052419
TI  - Centrifugal-Coated Quasi-Two-Dimensional Perovskite CsPb2Br5 Films for Efficient
      and Stable Light-Emitting Diodes.
AB  - The optical, structural, and electroluminescent (EL) characteristics of pure
      quasi-2D CsPb2Br5 were reported. We fabricated continuous, compact, well
      crystallized CsPb2Br5 films by centrifugal coating from a colloidal solution
      containing CsPb2Br5 nanoparticles. The centrifugal-coated CsPb2Br5 films have a
      photoluminescence quantum yield (PLQY) of ~35% because of its low-dimensional
      structure. Taking advantage of the high PLQY, we fabricated perovskite light
      emitting diodes (PeLEDs) with a centrifugal-coated CsPb2Br5 emitting layer
      exhibiting bright green EL, a maximum luminance of 7317 cd m-2, an and external
      quantum efficiency of 1.1%. Additionally, the EL color could be changed easily
      from green to red using a halogen exchange method. The half lifetime of our
      CsPb2Br5 PeLEDs reached around 6 h under continuous operation at 10 mA cm-2.

PMID- 29052420
TI  - A Quantitative Analysis of Factors Influencing Ease of Formation and sigma
      Bonding Strength of Oxa- and Thia-N-Heterocyclic Carbenes.
AB  - The index described previously (carbene relative energy of formation) has been
      extended to oxygen and sulfur heterocycles. This provides a quantitative overview
      of factors determining ease of formation of (i) neutral N-heterocyclic carbenes
      (NHCs) by deprotonation of heterocyclic salts and (ii) anionic NHCs by
      deprotonation of heterocyclic mesomeric betaines. The influence of the nature and
      ring position of oxygen and sulfur is discussed for a range of known and unknown
      systems. Attention is directed to unexplored systems of potential interest.

PMID- 29052421
TI  - Quantifying Solute Partitioning in Phosphatidylcholine Membranes.
AB  - Time-resolved fluorescence measurements were used to characterize and quantify
      solute partitioning into 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid
      vesicles as a function of solute concentration and temperature. The solutes,
      coumarin 152 (C152) and coumarin 461 (C461), both belong to a family of 7
      aminocoumarin dyes that have distinctive fluorescence lifetimes in different
      solvation environments. The two solutes differ in the 4-position where C152 has a
      trifluoromethyl group in place of C461's -CH3 group. In vesicle containing
      solutions, multiexponential fluorescence decays imply separate solute populations
      in the aqueous buffer, solvated in the vesicle headgroup region and solvated in
      the acyl chain bilayer interior, respectively. Fluorescence amplitudes, corrected
      for differences in radiative rates, are used to calculate absolute partition
      coefficients and average number of solutes per vesicle as a function of
      coumarin:lipid ratio and average number of solutes per vesicle. Results show that
      C152 has an ~10-fold greater affinity than C461 for lipid bilayers, despite both
      solutes having similar hydrophobicities as inferred from their log(P) values.
      Temperature-dependent partitioning data are used to calculate enthalpies and
      entropies of C152 partitioning as a function of concentration. These values are
      used to extrapolate to the infinitely dilute limit. Above and below the lipid gel
      liquid crystalline temperature, partitioning is exothermic with negative changes
      in entropy. In the vicinity of the transition temperature, these quantities
      change sign with DeltaHpart becoming endothermic (+70 kJ/mol) and entropically
      favored (DeltaSpart = +240 J/(mol.K)).

PMID- 29052422
TI  - Thiabicyclononane-Based Antimicrobial Polycations.
AB  - Bicyclo[3.3.1]nonane (BCN) polycations were synthesized by the reaction of the
      bivalent electrophile thiabicyclo[3.3.1]nonane dinitrate with a series of simple
      bis(pyridine) nucleophiles. Oligomers of moderate chain length were formed in a
      modular approach that tolerated the inclusion of functionalized and variable
      length linkers between the pyridine units. Post-polymerization modification via
      copper-catalyzed azide-alkyne cyloaddition was enabled by the inclusion of
      terminal alkyne groups in these monomers. Most of the resulting polymers, new
      members of the polyionene class, inhibited the growth of bacteria at the MUg/mL
      level and killed static bacterial cells at polymer concentrations of tens of
      ng/mL, with moderate to good selectivity with respect to lysis of red blood
      cells. While resistance to the BCN polymers was developed only very slowly over
      multiple passages, a degradable version of the polycation was observed to make E.
      coli cells more susceptible to other quaternary ammonium based antimicrobials.
      Solid substrates (glass and crystalline silicon) covalently functionalized with a
      representative BCN polycation were also able to repetitively kill bacteria in
      solution at high rates and with cleaning by simple sonication between exposures.

PMID- 29052424
TI  - The moderating effect of subjective age on the association between depressive
      symptoms and cognitive functioning in Korean older adults.
AB  - OBJECTIVES: Depressive symptoms are greatly associated with cognitive impairment
      in older adults. Recent growing body of literature has reported that the
      subjective perception of one's own age (subjective age) predicts both cognitive
      performance and mental well-being in old age. This study aims to examine whether
      subjective age moderates the association between depressive symptoms and
      cognitive functioning in a representative sample of Korean older adults. To
      address this research question, we employed the Stereotype-Embodiment Theory as a
      theoretical guide. METHOD: Data are from the 2016 Dementia Literacy Survey
      collected by Kyung Hee University, and 526 community-dwelling Korean older adults
      (ages 60-79) completed the questionnaire about depressive symptoms, cognitive
      functioning, and subjective age. RESULTS: According to the hierarchical
      regression analysis, both higher levels of depressive symptoms and older
      subjective age were associated with poorer cognitive functioning. Further
      analyses showed that subjective age attenuated the effect of depressive symptoms
      on cognitive functioning: when older adults have a higher level of depression,
      those with younger subjective age reported a higher level of cognitive
      functioning than those with older subjective age. CONCLUSION: Based on the
      findings from this study, both theoretical and practical implications were
      discussed.

PMID- 29052423
TI  - Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design,
      Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler
      Designed and Potent Trioxacarcin Analogues.
AB  - A streamlined total synthesis of the naturally occurring antitumor agents
      trioxacarcins is described, along with its application to the construction of a
      series of designed analogues of these complex natural products. Biological
      evaluation of the synthesized compounds revealed a number of highly potent, and
      yet structurally simpler, compounds that are effective against certain cancer
      cell lines, including a drug-resistant line. A novel one-step synthesis of
      anthraquinones and chloro anthraquinones from simple ketone precursors and
      phenylselenyl chloride is also described. The reported work, featuring novel
      chemistry and cascade reactions, has potential applications in cancer therapy,
      including targeted approaches as in antibody-drug conjugates.

PMID- 29052425
TI  - Inclusive state immigrant policies and health insurance among Latino,
      Asian/Pacific Islander, Black, and White noncitizens in the United States.
AB  - OBJECTIVES: Policy-making related to immigrant populations is increasingly
      conducted at the state-level. State policy contexts may influence health
      insurance coverage by determining noncitizens' access to social and economic
      resources and shaping social environments. Using nationally representative data,
      we investigate the relationship between level of inclusion of state immigrant
      policies and health insurance coverage and its variation by citizenship and
      race/ethnicity. METHODS: Data included a measure of level of inclusion of the
      state policy context from a scan of 10 policies enacted prior to 2014 and data
      for adults ages 18-64 from the 2014 American Community Survey. A fixed-effects
      logistic regression model tested the association between having health insurance
      and the interaction of level of inclusiveness, citizenship, and race/ethnicity,
      controlling for state- and individual-level characteristics. RESULTS: Latino
      noncitizens experienced higher rates of being insured in states with higher
      levels of inclusion, while Asian/Pacific Islander noncitizens experienced lower
      levels. The level of inclusion was not associated with differences in insurance
      coverage among noncitizen Whites and Blacks. CONCLUSIONS: Contexts with more
      inclusive immigrant policies may have the most benefit for Latino noncitizens.

PMID- 29052426
TI  - [Articles of the Hungarian Medical Journal from April, 1998].

PMID- 29052427
TI  - The joint ISPOR-ISPE Special Task Force on real-world evidence in health care
      decision making: an interview with Marc Berger.
AB  - Marc L Berger, MD, is a retired, part-time consultant. He recently became Chair
      of the Real World Evidence Advisory Board for SHYFT Analytics. Over a 25-year
      industry career, Marc has held senior-level positions at Pfizer, Inc.,
      OptumInsight, Eli Lilly and Company, and Merck & Co., Inc. His professional
      activities have included serving on committees for Center for Medicare and
      Medicaid Services (CMS), Agency for Healthcare Research and Quality (AHRQ),
      Patient-Centered Outcomes Research Institute (PCORI), the International Society
      for Pharmacoeconomics and Outcomes Research (ISPOR), Drug Information Association
      (DIA), and the editorial advisory boards of several journals. Marc has written or
      co-written more than 100 peer-reviewed articles, book chapters, and other
      publications on a range of topics including health services research, outcomes
      research, health economics, health policy, and the analysis of real-world data.

PMID- 29052428
TI  - Commentary: The challenge of ensuring access to mental health services for
      children and adolescents.

PMID- 29052429
TI  - Idle minds are the devil's tools? Coping, depressed mood and divergent thinking
      in older adults.
AB  - OBJECTIVES: The main aim was to test a causal relations model of the problem
      focused and emotion-focused coping styles, depressed mood, and divergent thinking
      (DT) in older adults. It was hypothesized that both forms of coping would have a
      significant effect on predicting depressed mood, and that problem-focused coping
      and depressed mood would have a significant effect on DT. METHOD: Participants
      were 135 subjects with ages ranging between 55 and 84 years old, who took part in
      a personal interview and filled out several questionnaires. The statistical
      analysis included structural equations models (SEM). RESULTS: The initial model
      led to a final model endorsed by the goodness of fit, composite reliability, and
      discriminant validity indexes. This model confirms a direct relationship between
      the two types of coping strategies and depressed mood (with the opposite sign),
      but not between rational coping and DT. Finally, depressed mood was also
      confirmed as a mediator variable between coping and DT. CONCLUSION: The type of
      coping is a clear predictor of mood in older adults. Advanced age decline is not
      necessarily translated into inefficacy in everyday problem solving especially in
      those who, through proble-focused coping, avoid depressed moods and maintain good
      levels of DT.

PMID- 29052430
TI  - Appropriate Targets for Search Advertising as Part of Online Gatekeeping for
      Suicide Prevention.
AB  - BACKGROUND: Gatekeeper training is an effective suicide prevention strategy.
      However, the appropriate targets of online gatekeeping have not yet been
      clarified. AIM: We examined the association between the outcomes of online
      gatekeeping using the Internet and the characteristics of consultation service
      users. METHOD: An advertisement to encourage the use of e-mail-based
      psychological consultation services among viewers was placed on web pages that
      showed the results of searches using suicide-related keywords. All e-mails
      received between October 2014 and December 2015 were replied to as part of
      gatekeeping, and the obtained data (responses to an online questionnaire and the
      content of the received e-mails) were analyzed. RESULTS: A total of 154
      consultation service users were analyzed, 35.7% of whom were male. The median age
      range was 20-29 years. Online gatekeeping was significantly more likely to be
      successful when such users faced financial/daily life or workplace problems, or
      revealed their names (including online names). By contrast, the activity was more
      likely to be unsuccessful when it was impossible to assess the problems faced by
      consultation service users. CONCLUSION: It may be possible to increase the
      success rate of online gatekeeping by targeting individuals facing
      financial/daily life or workplace problems with marked tendencies for self
      disclosure.

PMID- 29052431
TI  - Factors Influencing Professional Help-Seeking for Suicidality.
AB  - BACKGROUND: Evidence suggests that the majority of people with suicidality do not
      seek help. Little systematic evaluation of factors influencing professional help
      seeking has been done. AIMS: To systematically evaluate the factors that
      influence professional help-seeking for suicidality. METHOD: Published
      quantitative and qualitative studies in Medline and PsycInfo databases were
      reviewed following PRISMA. RESULTS: In all, 55 relevant studies were identified.
      Of these, 15 studies examined professional help-seeking intentions for perceived
      suicidal ideation, among people with or without suicidality; 21 studies examined
      professional help-seeking behavior among people with suicidality; and 19 studies
      examined suicidal decedents' health services use. Several potential important
      barriers were identified including high self-reliance, lack of perceived need for
      treatment, and stigmatizing attitudes toward suicide, toward mental health
      issues, and toward seeking professional treatment. The presence of suicidality
      and mental health issues was found to generally decrease help-seeking intentions
      for perceived suicidal ideation while facilitating actual service use. Social
      support and informal support from family and friends also played an important
      role in professional help-seeking. LIMITATIONS: Although the majority of the
      included studies were of sound quality, some of the factors identified in the
      review were assessed in relatively few studies, and most of the included studies
      were conducted in industrialized countries. CONCLUSION: Further quantitative and
      qualitative studies examining the potential important factors in broader
      community samples, especially in developing countries, are needed.

PMID- 29052432
TI  - Suicidal Risk Following the Termination of Romantic Relationships.
AB  - BACKGROUND: The termination of a romantic relationship is an established
      predictor of suicide attempt. Severing a relationship with a romantic figure can
      feel life-ending, based on attachment theory. AIMS: The primary goal of this
      study was to determine if specific risk markers for suicide are related to an
      individual's commitment level to the romantic relationship prior to its
      dissolution. METHOD: The purpose of this study was to examine if commitment and
      investment are linked with suicidal risk in a sample of adults (n = 208) in the
      United States ages 18-64 who experienced the break-up of a significant romantic
      relationship within the past 3 months. RESULTS: A structural equation model
      analysis revealed a significant association between commitment to the romantic
      relationship and suicidal risk when mediated by depression. This suggests that
      high commitment to the previous romantic relationship is indirectly associated
      with suicidal risk, indicating a need for increased attention to individuals who
      recently experienced a break-up. LIMITATIONS: This study is limited by its cross
      sectional design and by retrospective accounts of the previous relationships.
      CONCLUSION: This study indicates that high commitment to a romantic relationship
      may serve as a risk factor of depression and therefore of suicide when the
      relationship is terminated.

PMID- 29052433
TI  - Financial Sector Workers' Experiences of Managing Suicidal Clients.
AB  - BACKGROUND: Financial sector workers interface with indebted clients, who may be
      distressed and have heightened vulnerability to suicidality. AIM(S): This study
      examined the experiences of 10 Irish financial sector workers who had experiences
      of encountering distressed clients who discuss suicide. METHOD: Semistructured
      interviews (open-ended questions) were used. RESULTS: Interpretative
      phenomenological analysis (IPA) identified four themes, namely: (1) avoidance
      versus confrontation of reality (management of the debt); (2) role conflict
      (recovering the debt vs. supporting the client); (3) emotional impact and
      distancing from clients (coping with concerns for client welfare); (4) desire for
      support (practical and emotional training and support needs). LIMITATIONS: The
      frequency with which such clients were encountered was not assessed. CONCLUSION:
      These themes demonstrate the need to provide support to this group, and also the
      difficulties in providing training to manage suicidal clients in a context where
      the staff member's goal is to recover debt.

PMID- 29052434
TI  - A virtual clinic improves pneumococcal vaccination coverage among patients living
      with HIV at a Veterans Affairs Medical Center.
AB  - People living with the human immunodeficiency virus (HIV) should receive
      pneumococcal vaccinations as part of their routine health maintenance. Our goal
      was to create a "virtual clinic" to help increase rates of pneumococcal
      vaccination among people living with HIV without adding substantially to the
      workload of primary providers. We used administrative data from our Veterans
      Affairs (VA) medical center to identify a cohort of veterans living with HIV who
      were not current with either the 13-valent pneumococcal conjugate vaccine
      (PCV13), the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or both. We
      enrolled these individuals (n = 99) into a virtual clinic, notified providers via
      the electronic medical record and mailed letters to the veterans recommending
      they receive a pneumococcal vaccine. We also wrote orders for the appropriate
      pneumococcal vaccine that expired after 90 days. Among the virtual clinic cohort,
      38% (38/99) of patients received the recommended vaccine within 180 days.
      Concurrent with our intervention, the Veterans Health Administration deployed a
      system-wide pneumococcal vaccine clinical reminder that incorporated recent PCV13
      recommendations. To discern any effect of the virtual clinic beyond that of the
      clinical reminder, we compared the rate of PCV13 vaccinations among all HIV
      positive veterans at our institution to the equivalent population from 2 other VA
      medical centers in Ohio. With consideration of the VHA's system-wide clinical
      reminder, the proportion of HIV-positive patients who received PCV13 in the first
      90 days following the virtual clinic intervention was greater at our facility
      compared to another Ohio VA medical center (P < 0.05). The virtual clinic
      improved the pneumococcal vaccine coverage among HIV-positive veterans. These
      outcomes suggest that even in conjunction with a system-wide clinical reminder,
      the virtual clinic strategy improves vaccination rates among a high-risk
      population.

PMID- 29052435
TI  - High overall cardiovascular risk and mortality in patients with atrial
      fibrillation and diabetes: A nationwide report.
AB  - AIM: To describe nationwide complication patterns in patients with atrial
      fibrillation and diabetes mellitus. METHODS: All ( n = 326,832) patients in
      Sweden with non-valvular atrial fibrillation during 2006-2012 were identified,
      and information on events, comorbidities and pharmacological therapy was
      extracted using nationwide mandatory registers. Patients were followed until 31
      December 2013 and the mean follow-up time was 3.7 years (0.9-8 years). RESULTS:
      Diabetes was present in 17.7%. The most frequent events in those with and without
      diabetes were mortality (48.8% vs 36.4%; p < 0.001), heart failure (21.4% vs
      13.1%; p < 0.001), ischaemic stroke (8.2% vs 6.8%; p < 0.001), myocardial
      infarction (7.3% vs 4.3%; p < 0.001) and any bleeding (6.3% vs 5.2%; p < 0.001),
      respectively. Diabetes predicted mortality (hazard ratio = 1.28; 95% confidence
      interval = 1.25-1.31), combined event (first of mortality, heart failure,
      ischaemic stroke or myocardial infarction; hazard ratio = 1.22; 95% confidence
      interval = 1.20-1.25), single events and bleeding (hazard ratio = 1.12; 95%
      confidence interval = 1.06-1.19). The standardised mortality ratio for patients
      with atrial fibrillation and diabetes compared to the general population was 2.06
      (95% confidence interval = 2.00-2.12) and for patients with atrial fibrillation
      without diabetes was 1.33 (95% confidence interval = 1.31-1.35). CONCLUSION: In
      this real-world setting, patients with atrial fibrillation and diabetes have a
      high cardiovascular risk, with mortality and heart failure rates exceeding those
      for stroke.

PMID- 29052436
TI  - Prognostic impact of immunoparesis at diagnosis and after treatment onset in
      patients with light-chain amyloidosis.
AB  - OBJECTIVES: Immunoparesis (IP) is a risk factor associated with an unfavourable
      outcome in several plasma cell disorders. It has been suggested that its presence
      in light-chain (AL) amyloidosis could be associated with worse prognosis.
      However, the relevance of IP after treatment has not been evaluated to date. The
      aim of this study was to determine the prognostic impact of IP at diagnosis and
      one year after treatment onset in patients with AL amyloidosis. METHODS: The
      clinical records of 69 patients with AL amyloidosis treated at a single
      institution from January 2006 to January 2016 were included in the study.
      RESULTS: IP was observed in 27.5% of patients at diagnosis. The presence of IP
      was associated with a lower probability to achieve very good partial response or
      better after first-line treatment (37.8% versus 62.2%; p = .04). However, only in
      the group of patients treated with autologous stem cell transplantation (ASCT),
      the presence of IP resulted in a shorter progression-free survival (PFS) (30.2
      months versus not reached [NR]; p = .02) but not in overall survival (OS).
      Persistence of IP at one year after treatment onset was identified in only four
      (9.8%) of the 41 evaluable patients. In the ASCT group, the absence of IP at one
      year after treatment onset resulted in a longer median PFS and OS (NR versus 22.6
      months; p = .006; and NR versus 35.2 months; p < .001; respectively). In the
      multivariate analysis, the absence of IP at one year after treatment onset was
      independently associated with longer survival. CONCLUSION: IP at diagnosis has a
      negative impact on survival while its absence at one year after treatment is an
      independent marker for long-term survival.

PMID- 29052437
TI  - 5,6-dehydrokawain from the rhizome of Alpinia mutica Roxb. induced proangiogenic
      tumour-derived VEGF of HT-29 colorectal cancer.
AB  - Vascular endothelial growth factor (VEGF) is a glycoprotein vital to the
      regulation of vascular endothelial cells proliferation, migration and
      angiogenesis. The expression of VEGF is required for the formation of new blood
      vessels critical in supplying oxygen and nutrition in the course of
      tumorigenesis. The present study investigated the effect of 5,6-dehydrokawain
      isolated from the rhizomes of Alpinia mutica on VEGF expression in vitro using HT
      29 cell line. The results revealed that 5,6-dehydrokawain induced the expression
      of proangiogenic tumour-derived VEGF of HT-29 cells, which may explain the
      inability of 5,6-dehydrokawain in suppressing cancer cells proliferation.

PMID- 29052438
TI  - Prevalence of mutant ATTR cardiac amyloidosis in elderly African Americans with
      heart failure.

PMID- 29052440
TI  - Polarographic study on the presence of antibiotics in food.
AB  - EU and Italian laws dealing for the presence of antibiotics or, more in general,
      drags in food established limits for different kinds of food. Suitable rules
      exist about the medical treatment of cattle in relation to the production of milk
      and meat. The adoption of a procedure to check the respect of the law limits is
      necessary. In this paper, the presence of different classes of antibiotics in
      milk and in homogenised meat is investigated. Generally, HPLC methods are applied
      for this purpose. In this paper, the application of polarographic analysis is
      studied and the results are compared with the chromatographic ones. The
      comparison is relative to all the phases of analysis including the sample
      preparation. The results show the advantage of the proposed procedure.

PMID- 29052439
TI  - Predictors of mortality in hospital survivors with type 2 diabetes mellitus and
      acute coronary syndromes.
AB  - AIM: To define the predictors of long-term mortality in patients with type 2
      diabetes mellitus and recent acute coronary syndrome. METHODS AND RESULTS: A
      total of 7226 patients from a randomized trial, testing the effect on
      cardiovascular outcomes of the dual peroxisome proliferator-activated receptor
      agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute
      coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2 years.
      The independent mortality predictors were defined using Cox regression analysis.
      The predictive information provided by each variable was calculated as percent of
      total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular
      death contributing for 73% of mortality. The mortality prediction model included
      N-terminal proB-type natriuretic peptide (adjusted hazard ratio = 1.68; 95%
      confidence interval = 1.51-1.88; 27% of prediction), lack of coronary
      revascularization (hazard ratio = 2.28; 95% confidence interval = 1.77-2.93; 18%
      of prediction), age (hazard ratio = 1.04; 95% confidence interval = 1.02-1.05;
      15% of prediction), heart rate (hazard ratio = 1.02; 95% confidence interval =
      1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio = 1.11; 95%
      confidence interval = 1.03-1.19; 8% of prediction), haemoglobin (hazard ratio =
      1.01; 95% confidence interval = 1.00-1.02; 8% of prediction), prior coronary
      artery bypass (hazard ratio = 1.61; 95% confidence interval = 1.11-2.32; 7% of
      prediction) and prior myocardial infarction (hazard ratio = 1.40; 95% confidence
      interval = 1.05-1.87; 6% of prediction). CONCLUSION: In patients with type 2
      diabetes mellitus and recent acute coronary syndrome, mortality prediction is
      largely dominated by markers of cardiac, rather than metabolic, dysfunction.

PMID- 29052441
TI  - Investigational glucagon receptor antagonists in Phase I and II clinical trials
      for diabetes.
AB  - INTRODUCTION: Despite type 2 diabetes (T2D) being recognized as a bihormonal
      pancreatic disease, current therapies are mainly focusing on insulin, while
      targeting glucagon has been long dismissed. However, glucagon receptor (GCGr)
      antagonists are currently investigated in clinical trials. Area covered:
      Following a brief description of the rationale for antagonizing GCGr in T2D,
      lessons from GCGr knock-out mice and pharmacological means to antagonize GCGr, a
      detailed description of the main results obtained with GCGr antagonists in Phase
      I-II clinical trials is provided. The development of several small molecules has
      been discontinued, while new ones are currently considered as well as innovative
      approaches such as monoclonal antibodies or antisense oligonucleotides inhibiting
      GCGr gene expression. Their potential benefits but also limitations are
      discussed. Expert opinion: The proof-of-concept that antagonizing GCGr improves
      glucose control in T2D has been confirmed in humans. Nevertheless, some adverse
      events led to stopping the development of some of these GCGr antagonists. New
      approaches seem to have a better benefit/risk balance, although none has
      progressed to Phase III clinical trials so far. Pharmacotherapy of T2D is
      becoming a highly competitive field so that GCGr antagonists should provide clear
      advantages over numerous existing glucose-lowering medications before eventually
      reaching clinical practice.

PMID- 29052442
TI  - Denosumab for the treatment of bone disease in solid tumors and multiple myeloma.
AB  - Bone is a common site for malignant involvement, either as a site of metastasis,
      especially in breast or prostate cancer, or as a defining characteristic of the
      disease, as in multiple myeloma. Bone disease is a major source of morbidity, and
      half of patients with bone involvement develop skeletal-related events such as
      pathological fractures or cord compression requiring surgery and/or radiation.
      Skeletal involvement also increases mortality, as pathologic fractures increase
      the risk of dying by 20-40%. Osteoclast inhibition with bisphosphonates such as
      zoledronic acid and recently denosumab has been a significant improvement for
      bone disease. This review will focus on denosumab in the treatment of bone
      metastases and highlight the recent findings in multiple myeloma.

PMID- 29052443
TI  - Investigation and analysis of Galerina sulciceps poisoning in a canteen.
AB  - INTRODUCTION: Guizhou Province in China has an abundant resource of wild
      mushrooms, including numerous poisonous species which contain various toxins. The
      mortality rate from wild mushroom poisoning has been high in this area in recent
      years. Galerina sulciceps is a dangerously toxic mushroom which can be fatal if
      ingested. METHODS: we report on an epidemiological investigation of G. sulciceps
      poisoning which occurred in Duyun City of Guizhou Province. The characteristics
      of this species, its toxicity, observed clinical features, laboratory data,
      treatment modality, and prognosis were investigated in order to provide a
      reference point for the prevention and treatment of this kind of mushroom
      poisoning. RESULTS: Thirteen employees showed toxic symptoms after ingesting wild
      mushrooms the previous day in a company canteen. Clinical manifestation varied
      from gastroenteritis to hepatic and renal dysfunction. Most of the 13 patients
      presented with nausea, vomiting, abdominal pain, diarrhea, and elevated levels of
      biochemical indices of hepatic and renal function, during which transaminase
      concentration peaked within 48-72 h. At 48 hours post-ingestion, all patients had
      hemodialysis, in addition to supportive care for hepatic and renal injury with
      oral Silibinin and Shenshuaining. All acute renal injury had resolved by day 10,
      and liver transaminases had trended toward normal in all patients and they were
      discharged. At follow-up in 30 days, both liver and renal function had completely
      recovered in all. CONCLUSION: This poisoning occurs as a result of unintentional
      consumption of G. sulciceps, which is relatively rare in mushroom poisonings. All
      patients recovered fully after timely diagnosis and treatment. To prevent wild
      mushroom poisoning, the best preventive measure is to educate the public not to
      gather and eat any unidentified wild mushrooms.

PMID- 29052444
TI  - Heat shock proteins: a double-edged sword linking periodontal and cardiovascular
      diseases.

PMID- 29052445
TI  - Hot topics in transcatheter aortic valve implantation.

PMID- 29052446
TI  - Antiangiogenic phenylpropanoid glycosides from Gynura cusimbua.
AB  - A new phenylpropanoid glycoside, named alpha-L-rhamnopyranosyl-(1<->2)-beta-D-[4"
      (8E)-7-(3,4-dihydroxyphenyl)-8-propenoate, 1"-O-(7S)-7-(3,4-dihydroxyphenyl)-7
      methoxy-ethyl]-glucopyranoside (1), together with nine known compounds (2-10)
      were isolated from the active fraction (n-Butanol fraction) of Gynura cusimbua
      for the first time. The known compounds (2-10) were identified as phenylpropanoid
      glycosides on the basis of extensive spectral data and references. The
      antiangiogenic activities of compounds (1-10) were evaluated by MTT assay on
      HUVECs and wild-type zebrafish in vivo model assay. As a result, compounds 1, 6,
      7, 8 and 10 exhibited certain antiangiogenic activities.

PMID- 29052447
TI  - Insecticide activity of Baccharis dracunculifolia essential oil against
      Cochliomyia macellaria (Diptera: Calliphoridae).
AB  - The ethnobotanical uses of Brazilian plants for different injuries and diseases
      conjoined with local rich biodiversity represent an important resource for
      research and development. This study aimed to characterise BDEO and its in vitro
      activity on the third instar larvae (L3) of Cochliomyia macellaria. Groups of 20
      L3 were placed on filter paper impregnated with increasing concentrations of 5
      30% (v/v), equivalent to 0.79-4.77 MUL/cm2, solubilised in ethanol or acetone.
      The major constituents of BDEO were beta-pinene (9.94%), D-limonene (9.59%), beta
      nerolidol (7.93%), caryophyllene (7.69%), spathulenol (6.69), alpha-muurolene
      (6.74%) and alpha-pinene (5.31%). Lethal concentrations of 50% for BDEO on C.
      macellaria (LC50) after 24 and 48 h of exposure were 2.63 and 2.47 MUL/cm2 for
      ethanol and 9.58 and 8.11 MUL/cm2 for acetone, respectively. Furthermore, larvae
      cuticle abnormalities and adult deformity were observed. Our data confirm the
      effectiveness of BDEO as an ecofriendly product against blowflies.

PMID- 29052448
TI  - Using oncology real-world evidence for quality improvement and discovery: the
      case for ASCO's CancerLinQ.

PMID- 29052449
TI  - Resveratrol in management of bone and spinal cancers.
AB  - Bone cancer is a malignant primary tumour of the bone with different typing, such
      as, osteosarcoma, chondrosarcoma, Ewing's sarcoma and fibrosarcoma. Despite the
      clinical efficacy of conventional therapies of bone cancer, most patients
      eventually relapse and the disease remains incurable. Therefore, new therapeutic
      strategies are needed to improve patient outcome. In this review article, we have
      discussed the role of resveratrol in preventing bone and spinal cancers and
      therapeutics. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural
      polyphenol, which has been widely reported as an anticancer molecule. Resveratrol
      exhibits multiple tumour-suppressing activities in bone cancer by affecting a
      series of critical events. It has the protective effects against oxidative
      injury, possesses antiproliferative activity and induces apoptosis in cancer
      cells. Resveratrol might be a good option for the treatment of different types of
      bone and spinal cancers.

PMID- 29052450
TI  - Measuring the Implementation of Youth Empowerment Solutions.
AB  - Scholars have increasingly emphasized the importance of using evidence-based
      programs to promote health and prevent disease. While theoretically and
      empirically based programs may be effective in carefully controlled conditions,
      many fail to achieve desired outcomes when implemented in real-world settings.
      Ensuring high-quality implementation of health promotion programs is critically
      important as variation in implementation is closely associated with program
      effectiveness. The purpose of this article is to present methods used to document
      and assess the implementation of the Youth Empowerment Solutions (YES) program.
      We collected process evaluation data on 25 YES groups from 12 schools over a
      period of 4 years. The evaluation assessed four key aspects of delivery:
      fidelity, dose delivered, dose received, and program quality. We found wide
      variations in delivery for some measures, while others were more consistent
      across groups. These indicators of program delivery provided a strong basis for
      evaluating program implementation, taking actions to improve it, and ultimately,
      deepening understanding of program effectiveness. The study suggests a model for
      using multiple methods to collect and analyze data about aspects of program
      delivery to guide future implementations.

PMID- 29052451
TI  - Sesquiterpenes and lignans from the flower buds of Daphne genkwa and their nitric
      oxide inhibitory activities.
AB  - Chemical investigation of the Daphne genkwa has led to the isolation of four
      sesquiterpenes (1a/1b, 2 and 3), including one pair of sesquiterpene enantiomers
      (1a/1b), 1a is a new compound (+)-4-hydroxy-10-epirotundone, and twelve lignans
      (4-15). Their structures were elucidated by spectroscopic analysis, and the
      absolute configurations of 1a/1b were determined by CD analysis. All compounds
      were examined for their inhibitory effects on the nitric oxide (NO) production
      induced by lipopolysaccharide (LPS) in BV-2 microglial cells, and compounds 7-10
      exhibited pronounced inhibition on NO production with IC50 values in the range of
      5.8-10.2 MUM, being more active than the positive control, quercetin (IC50 = 17.0
      MUM).

PMID- 29052452
TI  - What is the role of Staphylococcus aureus and herpes virus infections in the
      pathogenesis of atopic dermatitis?
AB  - Atopic dermatitis (AD) is a chronic, relapsing disease. Genetic, environmental
      and immunological factors are involved in its pathophysiology. Individuals with
      AD have an increased predisposition to colonization and/or infection of the skin
      by various pathogens, especially Staphylococcus aureus and herpes simplex virus.
      The composition of their skin microbiome is also different, and changes during
      flares. The disease severity can be related to the degree of colonization by S.
      aureus. In addition, the presence of this bacterial species can predispose the
      host to more severe and disseminated viral infections. This article reviews the
      role of S. aureus and herpes virus infections and the skin microbiome in the
      pathogenesis of AD and their importance in the treatment and prevention
      strategies of this dermatosis.

PMID- 29052453
TI  - Review of epidemiology, clinical presentation, diagnosis, and treatment of common
      primary psychiatric causes of cutaneous disease.
AB  - Approximately half of all patients presenting to dermatologists exhibit signs and
      symptoms of psychiatric conditions that are either primary or secondary to
      cutaneous disease. Because patients typically resist psychiatric consult,
      dermatologists often are on the front line in evaluating and treating these
      patients. Accordingly, distinguishing the specific underlying or resulting
      psychiatric condition is essential for effective treatment. The etiology,
      epidemiology, clinical presentation, diagnosis, and first-line treatment of
      specific primary psychiatric causes of dermatologic conditions, including
      delusional infestation, Morgellons syndrome, olfactory reference syndrome, body
      dysmorphic disorder, excoriation disorder, trichotillomania, and dermatitis
      artefacta are discussed here, followed by a discussion of the recommended
      treatment approach with an overview of the different first-line therapies
      discussed in this review, specifically cognitive behavioral therapy, atypical
      antipsychotics, selective serotonin reuptake inhibitors, and tricyclic
      antidepressants. Included is a guide for dermatologists to use while prescribing
      these medications.

PMID- 29052455
TI  - New triterpene saponins from the roots of Acacia macrostachya (Mimosaceae).
AB  - Four new oleanane-type saponins, macrostachyaosides A, B, C, and D (1-4) were
      isolated from the roots of Acacia macrostachya. Their structures were elucidated
      on the basis of extensive 1D- and 2D-NMR data and HR-ESI-MS analyses. At
      concentrations of 100 MUM of each compounds, none of the tested compounds caused
      a significant growth reduction against HL60 cells.

PMID- 29052454
TI  - Surgical ethics: today and tomorrow.
AB  - Ethical behavior has always been deeply ingrained in surgical culture, but
      ethical deliberation has only recently become an important component of cardiac
      surgical practice. In our earlier review, we covered a range of issues including
      several related to informed consent, conflict of interest, professional self
      regulation and innovation, among many others. This update covers several topics
      of interest to cardiac surgeons and cardiologists, focusing on controversial
      issues specific to the practice of cardiothoracic surgery: informed consent,
      relations with hospitals and euthanasia and physician-assisted suicide. The
      future holds much uncertainty for cardiac surgical practice, research and
      culture, and we provide an update on ethical issues to serve as a platform for
      envisioning what is to come.

PMID- 29052456
TI  - Population density analysis for determining the protonation state of the
      catalytic dyad in BACE1-tertiary carbinamine-based inhibitor complex.
AB  - BACE1 is an aspartyl protease with a very relevant role in medicinal chemistry
      related to Alzheimer Disease since it has demonstrated to be a promising
      therapeutic target for inhibition and possible control for the progress of the
      peptide accumulation characteristic of this pathology. The enzymatic activity of
      this protein is given by the aspartic dyad, Asp93 and Asp289, which can adopt
      several protonation states depending on the chemical nature of its inhibitors,
      this is, monoprotonated, diprotonated and di-deprotonated states. In the present
      study, the analysis of the population density, for a series of protein-inhibitor
      molecular dynamics simulations, was carried out to identify the most feasible
      protonation state adopted by the catalytic dyad in the presence of tertiary
      carbinamine (TC) transition state analog inhibitors. The results revealed that
      the monoprotonated Asp289i state, in which the Asp93 and Asp289 residue side
      chains are deprotonated and protonated on the inner oxygen, respectively, is the
      most preferred in the presence of TC family inhibitors. This result was obtained
      after evaluating, for all 9 possible protonation state configurations, the
      individual and combined population densities of a set of parameters sensitive to
      protonation state of the Aspartic dyad, using an X-ray experimental BACE1/TC
      crystallographic structure as reference. This case study demonstrates again the
      usefulness of the concept of population density as a quantitative tool to
      establish the most stable system settings, among all possible, by measuring the
      level of occurrence of simultaneous events obtained from a sampling over time.
      These results will help to clear the phenomena related to the TCs inhibitory
      pathway, as well as assist in the design of better TC inhibitors against
      Alzheimer's protease.

PMID- 29052457
TI  - Effects of different heat-moisture treatments on the physicochemical properties
      of brown rice flour.
AB  - We evaluated the effect of heat-moisture treatment (HMT) on the main chemical
      components, physical properties, and enzyme activities of two types of brown rice
      flour: high-amylose Koshinokaori and normal-quality Koshiibuki. Five different
      HMTs using brown rice (moisture content was 12.0%) were assessed: 0.1 MPa/120 
      degrees C for 5 or 10 min, 0.2 MPa/134  degrees C for 5 or 10 min and 0.3 MPa/144
      degrees C for 10 min. HMT, decreased the alpha-amylase and lipase activities,
      and fat acidity, and slightly increased the dietary fiber and resistant starch
      levels. After 2 months' storage at 35  degrees C, rice samples that were treated
      with 0.2 MPa/134  degrees C or 0.3 MPa/144  degrees C for 10 min had a lower fat
      acidity than untreated samples, which would be useful for long-term storage and
      export of rice flour. And HMT exhibited inhibition of retrogradation in the
      pasting and physical properties, which is profitable to promote the qualities of
      the rice products.

PMID- 29052458
TI  - The Vogt family: Creators of diverse paths for women in biological research.
AB  - The life and careers of Cecile, Marthe and Marguerite Vogt are chronicled in this
      article during an era where women were not readily accepted in the upper echelons
      of academia. By exploring important questions, these women made major
      contributions to the broad base of scientific knowledge which impacted the fields
      of neurobiology in both the central and peripheral nervous systems, infectious
      disease, and oncogenesis. As a result, each was considered the elite of her
      respective field and achieved an enduring legacy.

PMID- 29052459
TI  - Paradoxical Thinking as a Conflict-Resolution Intervention: Comparison to
      Alternative Interventions and Examination of Psychological Mechanisms.
AB  - Conflict-resolution interventions based on the paradoxical thinking principles,
      that is, expressing amplified, exaggerated, or even absurd ideas that are
      congruent with the held conflict-supporting societal beliefs, have been shown to
      be an effective avenue of intervention, especially among individuals who are
      adamant in their views. However, the question as to why these interventions have
      been effective has remained unanswered. In the present research, we have examined
      possible underlying psychological mechanisms, focusing on identity threat,
      surprise, and general disagreement. In a small-scale lab study and a large-scale
      longitudinal study, we compared paradoxical thinking interventions with
      traditional interventions based on providing inconsistent information. The
      paradoxical thinking interventions led rightists to show more unfreezing of held
      conflict-supporting beliefs and openness to alternative information, whereas the
      inconsistency-based interventions tended to be more effective with the centrist
      participants. Both studies provide evidence that the effects were driven by
      identity threat, surprise, and lower levels of disagreement.

PMID- 29052460
TI  - More questions regarding the Danish health puzzle?

PMID- 29052461
TI  - Beyond the subjective experience of colour: An experimental case study of
      grapheme-texture synesthesia.
AB  - This study was a case investigation of grapheme-texture synestheste TH, a female
      who subjectively reported experiencing a visual association between grapheme and
      colour/texture. First, we validated the existence of a synesthetic association in
      an objective manner. Involuntarily elicited experience is a major hallmark that
      is common to different types of synesthetes. Our results indicated interference
      between physical and synesthetic texture, suggesting the involuntary occurrence
      of synesthetic textural experience. We analysed the behavioural measures using
      the EZ diffusion model. The result suggested that TH's synesthetic experience was
      dissociable from that of briefly trained associative processing of non
      synesthetes. Second, we investigated how the synesthetic experience of colour and
      texture dimensions was bound in the visual representation. We found that the
      interference effects of colour and texture were not independent. This suggested
      that in the elicited experience, the colour and texture features construct an
      integrated representation.

PMID- 29052462
TI  - Experimental-design-guided approach for the removal of atrazine by sono
      electrochemical-UV-chlorine techniques.
AB  - The aim of the present study was to investigate the electrochemical formation of
      free chlorine species (HOCl/ClO-) and their subsequent use for the degradation of
      the pesticide atrazine. Initially, the process of electrochemical-free chlorine
      production was investigated using a bench-scale electrochemical flow-cell. The
      most significant variables (electrolyte concentration ([NaCl]) and inter
      electrode gap) of the process were obtained using a 23 factorial design and the
      optimum process conditions (1.73 mol L-1 and 0.56 cm) were determined by a
      central composite design. Following optimization of free chlorine production,
      three degradation techniques were investigated, individually and in combination,
      for atrazine degradation: electrochemical, photochemical and sonochemical. The
      method using the techniques in combination was denominated sono-photo-assisted
      electrochemical degradation. Constant current assays were performed and the sono
      photo-assisted electrochemical process promoted more efficient removal of
      atrazine, achieving total organic carbon removal of ~98% and removal of atrazine
      to levels below the detection limit (>99%) in under 30 min of treatment.
      Furthermore, the combination of three techniques displayed lower energy
      consumption, and phytotoxicity tests (Lactuca sativa) showed that there was no
      increase in toxicity.

PMID- 29052463
TI  - Hot and cool executive function in children and adolescents with autism spectrum
      disorder: Cross-sectional developmental trajectories.
AB  - The development of executive function (EF) in autism spectrum disorder (ASD) has
      only been investigated using "cool"-cognitive-EF tasks. Little is known about the
      development of "hot"-affective-EF and whether it follows a similar developmental
      pathway. This study employed a cross-sectional developmental trajectories
      approach to examine the developmental changes in cool (working memory,
      inhibition, and planning) and hot EF (delay discounting and affective decision
      making) of ASD participants (n = 79) and controls (n = 91) relative to age and
      IQ, shedding more light on the hot-cool EF organization. The developmental
      trajectories of some aspects of cool EF (working memory and planning) differed
      significantly as a function of age in ASD participants relative to controls. For
      both hot EFs, no significant age-related changes were found in either group.
      These findings extend our understanding regarding the maturation of EF from
      childhood through adolescence in ASD.

PMID- 29052464
TI  - Longitudinal study of objective and subjective cognitive performance and
      psychological distress in OEF/OIF Veterans with and without traumatic brain
      injury.
AB  - OBJECTIVE: To describe changes in post-deployment objective and subjective
      cognitive performance in combat Veterans over 18 months, relative to traumatic
      brain injury (TBI) status and psychological distress. METHOD: This prospective
      cohort study examined 500 Veterans from Upstate New York at four time points, six
      months apart. TBI status was determined by a structured clinical interview.
      Neuropsychological instruments focused on attention, memory, and executive
      functions. Subjective cognitive complaints were assessed with the Neurobehavioral
      Symptom Inventory (NSI). A psychological distress composite included measures of
      post-traumatic stress disorder (PTSD), depression, and generalized anxiety.
      RESULTS: Forty-four percent of the sample was found to have sustained military
      related TBI, 97% of which were classified as mild (mTBI), with a mean time since
      injury of 41 months. Veterans with TBI endorsed moderate cognitive symptoms on
      the NSI. In contrast to these subjective complaints, mean cognitive test
      performance was within normal limits at each time point in all domains,
      regardless of TBI status. Multilevel models examined effects of TBI status, time,
      and psychological distress. Psychological distress was a strong predictor of all
      cognitive domains, especially the subjective domain. Substantial proportions of
      both TBI+ and TBI- groups remained in the clinically significant range at the
      initial and final assessment for all three distress measures, but the TBI+ group
      had higher proportions of clinically significant cases. CONCLUSIONS: Objective
      cognitive performance was generally within normal limits for Veterans with mTBI
      across all assessments. Psychological distress was elevated and significantly
      related to both objective and subjective cognitive performance.

PMID- 29052466
TI  - Edgar Leigh Collis: Industrial lung disease and ergonomics.
AB  - Edgar Collis was appointed as the second Medical Inspector of Factories in 1908,
      holding the post until the outbreak of the First World War when he became Medical
      Director of the Ministry of Munitions. After the war, he was appointed to the
      chair in public health in the University of Wales. He held this post while living
      in Lossiemouth in Scotland, some 570 miles distant. His research interests were
      in industrial lung disease, industrial hygiene, and the health of coal miners. He
      made important contributions to the first and third subjects, but was a less
      significant figure in the field of industrial hygiene. Among his achievements
      were the recognition of the relationship between silicosis and tuberculosis, the
      harmful effects of non-silicaceous coal dust, and the need to fit the worker to
      the job, and the job to the worker.

PMID- 29052465
TI  - Evaluating the roles of left middle frontal gyrus in word production using
      electrocorticography.
AB  - To assess the specific roles of left middle frontal gyrus (LMFG) in word
      production, electrocorticography signals were recorded from an epilepsy patient
      when he participated in language tasks. We found three sites of LMFG showed high
      gamma perturbations with distinct patterns across tasks; and neural activities
      elicited in the same tasks shared similar patterns, while those elicited by
      stimuli leading to the same articulations did not. These findings confirmed that
      the LMFG takes active parts in word production, and suggested that it may serve
      as a temporal perceptual information storage space, supporting the hierarchical
      state feedback control model of word production.

PMID- 29052467
TI  - The effect of level of injury and physical activity on heart rate variability
      following spinal cord injury.
AB  - OBJECTIVE/BACKGROUND: To assess frequency domain heart rate variability (HRV)
      parameters at rest and in response to postural autonomic provocations in
      individuals with spinal cord injury (SCI) and investigate the autonomic
      influences on the heart of different physical activities. DESIGN: Cross-sectional
      study. METHODS: Ten subjects with complete cervical SCI and fourteen subjects
      with complete low thoracic SCI were prospectively recruited from the community
      and further divided in sedentary and physically active groups, the latter defined
      as regular weekly 4 hour physical activity for the preceding 3 months. Sixteen
      healthy individuals matched for sex and age were recruited to participate in the
      control group. The Low Frequency (LF), High Frequency (HF) powers and the LF/HF
      ratio of HRV were measured from continuous electrocardiogram (ECG) recordings at
      rest and after sitting using a fast Fourier transformation. OUTCOME MEASURES: The
      LF,HF, and the LF/HF ratio at rest and after sitting. RESULTS: A significant
      decrease in all HRV parameters in patients with SCI was found compared to
      controls. The change in HF, LF and LF/HF following sitting maneuver was
      significantly greater in controls as compared with the SCI group and greater in
      subjects with paraplegia as compared to subjects with tetraplegia. Better HRV
      values and enhanced vagal activity appears to be related to the type of physical
      activity in active subjects with paraplegia. CONCLUSION: In this cohort of
      subjects spectral parameters of HRV were associated with the level of the injury.
      Passive standing was associated with higher HRV values in subjects with
      paraplegia.

PMID- 29052468
TI  - Evaluation of the content of TiO2 nanoparticles in the coatings of chewing gums.
AB  - Titanium dioxide is a metal oxide used as a white pigment in many food
      categories, including confectionery. Due to differences in the mass fraction of
      nanoparticles contained in TiO2, the estimated intakes of TiO2 nanoparticles
      differ by a factor of 10 in the literature. To resolve this problem, a better
      estimation of the mass of nanoparticles present in food products is needed. In
      this study, we focused our efforts on chewing gum, which is one of the food
      products contributing most to the intake of TiO2. The coatings of four kinds of
      chewing gum, where the presence of TiO2 was confirmed by Raman spectroscopy, were
      extracted in aqueous phases. The extracts were analysed by transmission electron
      microscopy (TEM), X-ray diffraction, Fourier Transform Raman spectroscopy, and
      inductively coupled plasma atomic emission spectroscopy (ICP-AES) to establish
      their chemical composition, crystallinity and size distribution. The coatings of
      the four chewing gums differ chemically from each other, and more specifically
      the amount of TiO2 varies from one coating to another. TiO2 particles constitute
      the entire coating of some chewing gums, whereas for others, TiO2 particles are
      embedded in an organic matrix and/or mixed with minerals like calcium carbonate,
      talc, or magnesium silicate. We found 1.1 +/- 0.3 to 17.3 +/- 0.9 mg TiO2
      particles per piece of chewing gum, with a mean diameter of 135 +/- 42 nm. TiO2
      nanoparticles account for 19 +/- 4% of all particles, which represents a mass
      fraction of 4.2 +/- 0.1% on average. The intake of nanoparticles is thus highly
      dependent on the kind of chewing gum, with an estimated range extending from 0.04
      +/- 0.01 to 0.81 +/- 0.04 mg of nano-TiO2 per piece of chewing gum. These data
      should serve to refine the exposure scenario.

PMID- 29052469
TI  - Vitamin D and L-Isoleucine Promote Antimicrobial Peptide hBD-2 Production in
      Peripheral Blood Mononuclear Cells from Elderly Individuals.
AB  - Elderly individuals are susceptible to develop infectious diseases; promoting
      innate immunity to prevent infections is a key issue. Human beta-defensin-2 (hBD
      2) is an antimicrobial peptide with antimicrobial and immunomodulatory
      properties. L-isoleucine and vitamin D are important molecules that induce hBD-2.
      The Aim of this study was to determine the use L-isoleucine and Vitamin D to
      induce hBD-2 in cells from healthy elderly individuals and elderly individuals
      with recurrent infections. We explored three groups: young adults (n = 20) used
      as control group, elderly adults (n = 18) and elderly with recurrent infections
      (n = 11). PBMCs (peripheral blood mononuclear cells) were isolated from the
      different groups and then were treated with L-isoleucine or vitamin D3. hBD-2
      concentration was assessed with a sandwich enzyme Immunosorbent assay by
      triplicate. Using the vehicle as a mock control. Our results showed that a
      percentage of the individuals responded to the treatments producing hBD-2 (p <
      0.05). These results showed that both molecules induced hBD-2 in elderly
      individuals and can be potentially used as prophylactic therapy to decrease
      infection diseases rates in this vulnerable group.

PMID- 29052470
TI  - The Potential of Fermentation and Contamination of Teff by Soil to Influence Iron
      Intake and Bioavailability from Injera Flatbread.
AB  - The high phytic acid (PA) concentration in the diet based on teff injera is a
      likely contributing cause of iron defi ciency in Ethiopia. We monitored PA during
      teff injera fermentation in 30 households in Debre Zeyit, Ethiopia and evaluated
      its infl uence on iron bioavailability, considering contaminant soil iron in teff
      fl our. After fermentation (48h), mean PA concentration in injera batter
      decreased from 0.87 to 0.58 g/100 g dm (P < 0.001). Low phytase activity in teff
      fl our (0.44 MUmol phosphate/min/g) and a rapid drop in pH, indicated that PA
      degradation was driven by microbial phytases. The iron concentration in injera
      batter among the households ranged widely from 14.5-160.4 mg/100 g dm (mean: 34.7
      mg/100 g dm) principally due to contamination with soil. Estimated intrinsic iron
      concentration of teff based on the strong correlation between total iron and
      aluminium concentrations (P < 0.001; aluminium concentrations in injera batter:
      28.7-184.9 mg/100 g dm) was 4.4 mg/100 g dm, indicating that 86-97 % is extrinsic
      iron from soil. The median daily iron intakes from 3-day weighed food records in
      10 young children were 18.9 mg/day including soil iron vs. 4.9 mg/day without
      soil iron (P < 0.01). The PA:iron molar ratios indicated low iron bioavailability
      from teff injera, particularly when soil iron was excluded. Traditional
      fermentation thus has a modest infl uence on PA levels and more complete
      degradation is needed to improve iron bioavailability. There is an urgent need to
      better understand the bioavailability of contamination iron from soil before
      considering national fortifi cation or biofortifi cation strategies in Ethiopia.

PMID- 29052471
TI  - A Review About Lycopene-Induced Nuclear Hormone Receptor Signalling in
      Inflammation and Lipid Metabolism via still Unknown Endogenous Apo-10'
      Lycopenoids.
AB  - Lycopene is the red pigment in tomatoes and tomato products and is an important
      dietary carotenoid found in the human organism. Lycopene-isomers, oxidative
      lycopene metabolites and apo-lycopenoids are found in the food matrix. Lycopene
      intake derived from tomato consumption is associated with alteration of lipid
      metabolism and a lower incidence of cardiovascular diseases (CVD). Lycopene is
      mainly described as a potent antioxidant but novel studies are shifting towards
      its metabolites and their capacity to mediate nuclear receptor signalling. Di
      /tetra-hydro-derivatives of apo-10'-lycopenoic acid and apo-15'-lycopenoic acids
      are potential novel endogenous mammalian lycopene metabolites which may act as
      ligands for nuclear hormone mediated activation and signalling. In this review,
      we postulate that complex lycopene metabolism results in various lycopene
      metabolites which have the ability to mediate transactivation of various nuclear
      hormone receptors like RARs, RXRs and PPARs. A new mechanistic explanation of how
      tomato consumption could positively modulate inflammation and lipid metabolism is
      discussed.

PMID- 29052472
TI  - Extraction and reliable determination of acrylamide from thermally processed
      foods using ionic liquid-based ultrasound-assisted selective microextraction
      combined with spectrophotometry.
AB  - Acrylamide (AAm) is a carcinogenic chemical that can form in thermally processed
      foods by the Maillard reaction of glucose with asparagine. AAm can easily be
      formed especially in frequently consumed chips and cereal-based foods depending
      on processing conditions. Considering these properties of AAm, a new, simple and
      green method is proposed for the extraction of AAm from thermally processed food
      samples. In this study, an ionic liquid (1-butyl-3-methylimidazolium
      tetrafluoroborate, [Bmim][BF4]) as extractant was used in the presence of a
      cationic phenazine group dye, 3,7-diamino-5-phenylphenazinium chloride (PSH+,
      phenosafranine) at pH 7.5 for the extraction of AAm as an ion-pair complex from
      selected samples. Under optimum conditions, the analytical features obtained for
      the proposed method were as follows; linear working range, the limits of
      detection (LOD, 3Sb/m) and quantification (LOQ, 10Sb/m), preconcentration factor,
      sensitivity enhancement factor, sample volume and recovery% were 2.2-350 ug kg-1,
      0.7 ug kg-1, 2.3 ug kg-1, 120, 95, 60 mL and 94.1-102.7%, respectively. The
      validity of the method was tested by analysis of two certified reference
      materials (CRMs) and intra-day and inter-day precision studies. Finally, the
      method was successfully applied to the determination of AAm levels in thermally
      processed foods using the standard addition method.

PMID- 29052473
TI  - A study of attendance and filling in of pre-appointment questionnaires in an
      outpatient clinical psychology service.
AB  - This study looked at whether filling in pre-appointment questionnaires was
      related to attendance in an adult clinical psychology out-patient service.
      Comparisons were made between attenders who filled in forms, attenders who did
      not fill in forms, non-attenders who filled in forms and non-attenders who did
      not fill in forms. The variables compared were: age, source of referral, reason
      for referral, gender, Health Authority, ethnic origin, marital status, level of
      anxiety (BAI), level of depression (BDI) and severity of symptoms (SCL-90).
      Attendance was much higher in those who filled in pre-appointment questionnaires
      (75% v. 35%). In addition, non-attenders who filled in questionnaires were
      younger than most of the other groups; attendance rates were raised with
      consultant referrals; GP referred clients were less likely to fill in
      questionnaires; and, among form fillers, non-attenders were more likely to be
      single. The results are discussed with reference to their service implications.

PMID- 29052474
TI  - A trial to determine any difference between two and three times a week ECT in the
      rate of recovery from depression.
AB  - This study considers the difference in outcome between the two most commonly used
      frequencies of ECT administration, two and three times a week, in a standard
      clinical setting. Forty-one subjects who satisfied ICD-10 criteria for major
      depressive episode were randomly allocated to twice or three times a week ECT.
      HDRS (17-item) and MMSE scores were performed pre-treatment, during treatment and
      post-treatment. The mean number of ECTs in the two and three times a week groups
      were 5.90 and 6.85 and the mean length of treatment course (days) was 18.82 and
      16.65, differences were statistically significant. There were dramatic
      improvements in HDRS scores in both groups but there were no statistically
      significant differences in HDRS scores between the groups during treatment.
      However, the group that received ECT two times a week showed significant lower
      HDRS scores in the week following the end of the ECT course. not differ between
      the groups. We concluded that ECT given three times a week provides no advantage
      over twice a week administration. Therefore, twice a week ECT is the preferred
      frequency. respectively. None of these statistically MMSE scores did.

PMID- 29052475
TI  - Minimising interventions in the treatment and prevention of depression. Taking
      the consequences of the 'Dodo Bird Verdict'.
AB  - Research has shown that the different psychotherapeutic treatments in depression
      are equally effective. This could be accounted for by the non-specific factors,
      which all therapies have in common. On the other hand, too little is known about
      the effectiveness of the therapies in different groups of patients. Research has
      shown that the format of the psychotherapies can be changed in several aspects
      without a reduction in effectiveness.

PMID- 29052476
TI  - How predictable is violence and suicide in community psychiatric practice?
AB  - There has been concern about the danger from psychiatric patients being treated
      in the community. We sought to assess the level of risk of violence and suicide
      in patients seen routinely by a community mental health team. Risk assessment
      questionnaires were completed by community mental health team professionals for
      all contacts with all patients seen by the team over a 1-month period. Twenty-six
      per cent (81/318) of patients seen were considered at 'moderate' or higher risk
      of suicide and 23% (73/ 318) at risk of violent behaviour. The variables best
      identifying those judged at risk of suicide were previous episodes of depressive
      illness and previous deliberate self-harm. The variables identifying risk of
      violence were previous violence to person or property, specific threats towards
      another, expression of emotions related to violence in the mental state
      examination and absence of previous depressive illness. A large number of
      patients seen by the community teams are at risk of suicide and violence; yet
      suicide or incidents of serious violence are rare. This highlights the difficulty
      in accurate prediction and the limits of risk management strategies recommended
      by inquiries following such events.

PMID- 29052477
TI  - Suicide in schizophrenia. A review of the literature.
AB  - This article reviews research from the 1960s to the present pertaining to suicide
      in people suffering with schizophrenia. An attempt has been made to examine
      suggested risk factors and generate recommendations for management, with
      particular attention to recent Department of Health guidelines regarding the care
      of the severely mentally ill. The literature was reviewed using Medline and
      PsychInfo, supplemented with a manual literature search. The studies reviewed
      were of variable quality. Many were limited by small numbers, lack of control
      groups and diagnostic heterogeneity. In combination with the low base-rate of
      suicide, and the relative homogeneity within groups of patients with
      schizophrenia, prediction remains problematic. Current initiatives suggest
      increased supervision of the at-risk population with little emphasis on
      attempting to reduce suicidal intent. There remains a need for continuing
      research into this difficult area of management. Specific areas for consideration
      include the management of hopelessness and depression in this group of patients,
      and the effect of the environment. The effect of the living environment, as well
      as the ongoing reductions in in-patient hospital beds and the current emphasis on
      increased turnover merit reappraisal.

PMID- 29052478
TI  - Stigma, discrimination and social exclusion: What's in a word?
AB  - There is mounting evidence that British service users face pervasive
      discrimination in areas of life ranging from work to parenting, insurance to
      driving licenses. Some studies suggest that certain forms of discrimination have
      increased during the 1990s, perhaps because of saturation media coverage of the
      supposed- but not actual- rise in homicides committed by people with mental
      health problems. One of the key concepts used to investigate the problems that
      users of mental health services face in their relationships to other people, and
      to society at large, is 'stigma'. This concept is used to frame questions of
      public attitudes about mental illness, users' self-perceptions and the
      unfavourable treatment they receive. It is often stated or implied that if we can
      break down 'stigma' we can transform users' position in society, their
      opportunities and wellbeing. This paper examines the limitations of both the
      concept of 'stigma' and the way it is applied, and reviews the growing literature
      on discrimination, which is seen as a more promising model on which to base
      social change.

PMID- 29052479
TI  - An epidemiological survey of communal establishment residents: Implications for
      mental health purchasers.
AB  - Psychiatric morbidity rates and use of specialist services were determined for
      adults living in communal establishments situated within an inner-city area.
      characteristics of residents were ascertained. Most people living in residential
      homes for the mentally ill had a psychiatric disorder (94%) and of these the
      majority were in contact with specialist services (97%). Similar results emerged
      for residents in the smaller hostels (with less than 10 residents) designated for
      the mentally ill. Even in the remaining smaller establishments and the larger
      hostels (with 10 or more residents), catering primarily for homeless people,
      almost half (49%) the residents had mental health problems. Furthermore, only
      around one-third (38%) were in receipt of psychiatric care. The relevance of
      these and other findings for purchasers of mental health services are discussed.
      The location of these facilities and the.

PMID- 29052480
TI  - Clients' perceptions of outcome following contact with a community mental health
      team.
AB  - Forty-five clients of a community mental health team (CMHT) were followed-up
      between 12 and 18 months after their initial contact with the service, and asked
      about their perceptions of outcome. Psychological ill-health at follow-up was
      also measured using the General Health Questionnaire (GHQ). The commonest mental
      health problems at referral were anxiety and/or depression, and threequarters had
      one or more significant personal/social problems. 5 or more on the GHQ at follow
      up, and reports of having received no help from the CMHT with mental health
      problems were associated with higher GHQ scores. help from the CMHT with their
      mental health problems than they did with their personal/social problems. Those
      who received no help with personal/social problems were less likely to report
      receiving help with mental health problems. Although clients had also sought help
      from sources other than the CMHT, these were mostly informal or voluntary.
      intervene effectively with clients' personal/social problems may limit the CMHT's
      capacity to improve their mental health. Forty-four per cent of clients scored
      Clients reported that they received more These findings suggest that inability
      to.

PMID- 29052481
TI  - Editorial Homeless in Cambridge?

PMID- 29052483
TI  - A survey of patient and keyworker satisfaction with the Gloucester mental health
      rehabilitation service.
AB  - Despite well described methodological problems, previous studies have
      consistently found patients to report reasonable satisfaction with their mental
      health treatment. Few studies have compared patient and mental health
      professionals' levels of satisfaction. rehabilitation case register were
      surveyed. Satisfaction with six aspects of care was assessed by a 5- point Likert
      rating scale, generating raw scores in each domain and a cumulative Total
      Satisfaction Score. Satisfaction among patients and their keyworkers were
      assessed on the same scale. Patients and keyworkers were more likely to be
      satisfied than dissatisfied with most aspects of their care. Patients had lowest
      satisfaction with knowledge of treatment, keyworkers with the patient's finances.
      Except for satisfaction with their treatment by the local satisfaction scores
      than keyworkers in all domains. Patient and keyworker satisfaction scores were at
      best weakly correlated. Other than for in-patient and compulsory treatment
      status, there was no significant association between satisfaction and
      demographic/illness-related factors, including psychopathology, insight,
      knowledge of treatment and cognitive function. The weak relationship between
      patient and keyworker satisfaction suggests a need for caution in interpreting
      our view of our patients' care. The findings imply problems in communicating
      about treatment with people suffering from severe mental illness. Assessment of
      patient satisfaction may be a useful component of individual care planning.
      174/199 (87%) patients on the Gloucester community, patients had significantly
      lower.

PMID- 29052484
TI  - Letter from Okinawa Mental health and community groups.

PMID- 29052485
TI  - Health literacy among Danish university students enrolled in health-related study
      programmes.
AB  - AIMS: It is important to address people's health literacy when providing health
      care. Health professionals should be aware of, and have insight into, people's
      health literacy when they provide health services. Health professionals need to
      be health literate themselves. We examined the level of health literacy in
      students in Denmark attending one of four full university programmes related to
      health and investigated how their health literacy was associated with their
      sociodemographic background. METHODS: The health literacy level of the students
      was measured using the multi-dimensional Health Literacy Questionnaire (HLQ)
      supplemented with sociodemographic questions. The questionnaire was administrated
      through the students' Facebook groups. The students were enrolled in courses on
      health informatics, medicine, molecular biomedicine or public health. Out of a
      total of 7663 students, 630 responded to the questionnaire. RESULTS: No sex
      difference was found although female students scored higher than male students in
      domain 4 (social support for health). Students attending the public health
      programme tended to score higher and those attending molecular biomedicine tended
      to score lower in the HLQ. There was a positive correlation between HLQ scores
      and the educational level of the students' parents. If one of their parents was
      employed in the health care sector, the HLQ score tended to be higher in domains
      1 and 4. Students who had been hospitalized also tended to score higher in
      domains 1, 5 and 6. CONCLUSIONS: Students' health literacy relates to their
      personal background and educational path. This may be of importance when planning
      curricula and educational activities, including cross-disciplinary courses.

PMID- 29052486
TI  - Lipase-catalyzed reactions in vesicles as an approach to vesicle self
      reproduction.
AB  - As a continuation of our endeavor to find conditions under which bounded
      aggregate structures are able to self-reproduce, we have investigated the
      reactivity of lipase, both in free solution and vesicle-entrapped, against mixed
      oleic acid/oleate/ethyl oleate vesicles. Three types of vesicles have been
      prepared and characterized: (A) oleic acid/oleate vesicles; (B) oleic
      acid/oleate/ethyl oleate vesicles; and (C) lipase containing oleic acid/oleate
      vesicles. Long time stability studies by quasi elastic light scattering show that
      whereas (B) and (C) vesicles remain stable with a diameter of 110-130 nm and
      monodisperse for over a period of one month, vesicles (A) separated from an
      initial single population of 105 nm diameter into two populations, having
      respectively 70 nm diameter (more than 95% of the particles) and 180-210 nm
      diameter (less than 5% of the total population). In the case of vesicles (C), it
      could be shown that the enzyme remains localized inside the vesicles and it does
      not protrude into the water bulk phase. The enzymatic hydrolysis of ethyl oleate
      (which is water-insoluble) incorporated in the B-vesicles was studied under two
      configurations: (I) by adding lipase externally to the B-vesicles; (II) by mixing
      vesicles (B) and vesicles (C). In both cases, the reaction progressed to 100%
      hydrolysis. In the first case, the reaction was attended by an increase of the
      number of vesicles, and since this hydrolysis reaction takes place within the
      boundary of the parent vesicles, the criteria of autopoietic self-reproduction of
      vesicles are satisfied. In the case (II) instead, no increase of the population
      number of particles could be detected. The possible reasons for this difference
      are discussed.

PMID- 29052487
TI  - A Novel Colourimetric Homogeneous Liposomal Immunoassay Using Sulphorhodamine B.
AB  - The dye, Sulphorhodamine B, was entrapped within liposomes prepared by the
      reverse evaporation technique. Marked differences in absorption spectra were
      found when free and entrapped dyes were compared, with a shift in the wavelength
      of maximum absorption. When entrapped dye was released by lysis of the liposomes,
      for example by detergent, the absorption spectrum reverted to that of free dye.
      This absorption change was employed in a novel marker system for complement
      mediated immunoassay. As a model assay, human serum albumin was measured using
      this approach. Liposomes which had been coated with albumin were incubated with
      anti-albumin antibody and complement and the resulting absorption change measured
      using an automated spectrophotometric analyser. The decrease in absorption change
      on the addition of albumin formed the basis of a competitive homogeneous
      immunoassay for human serum albumin. Using purified albumin as a standard, a
      correlation of 0.96 was obtained when the albumin in human serum was measured in
      the liposomal assay and the results compared to measurements using a bromocresol
      green method.

PMID- 29052488
TI  - Thermolabile Liposomes with a High Fusion Efficacy at 42 degrees C can be Made of
      Dipalmitoylphosphatidylcholine/Fatty Alcohol Mixtures in the Molar Ratio of 1/2.
AB  - Liposomes made of dipalmitoylphosphatidylcholine (DPPC2), dipalmitoyl
      phosphatidylglycerol (DPPG), and different long-chain fatty alcohols were
      investigated with respect to their colloidal stability, chain-melting phase
      transition temperature, and temperature dependent inter-vesicle fusion. In
      particular, the practical usefulness of the stoichiometric 1/2 (mol/mol) mixtures
      of the phospholipids and fatty alcohols, mainly elaidoyl alcohol (EL-OH) were
      studied. The mole fraction of DPPG in the bilayers of such vesicles affects
      crucially the colloidal stability of the resulting lipid suspensions; at least 15
      mol-% of DPPG (relative to DPPC) must be incorporated into the bilayers in order
      to make the liposome suspension colloidally sufficiently stable at room
      temperature. The corresponding DPPC/DPPG/EL-OH (0.85/0.15/2) mixed lipid vesicles
      undergo a lamellar-gel to inverted hexagonal (HIT) phase transition at 52.7
      degrees C, however, and then fuse and aggregate massively. The related phase
      transition temperature of the DPPC/DPPG/palmitelaidoyl alcohol (0.85/0.15/2)
      mixture is 48.4 degrees C. This indicates that the chain-melting phase transition
      temperature of the investigated lipid mixtures is rather sensitive to the alcohol
      chain-length. This transition temperature is independent, however, of the bulk
      proton concentration in the pH region between 4.9 and 7.2. Stoichiometric 1/2
      mixtures of phospholipids and EL-OH have a high propensity for the inter-vesicle
      fusion at 42 degrees C and neutral pH. The reason for such fusion 10 degrees C
      below the lamellar-to-nonlamellar phase transition temperature are the defects
      that are generated during the chain-melting of the (partly segregated)
      phospholipid component at 42 degrees C; the proximity of the lamellar to non
      lamellar phase transition temperature of the phospholipid/fatty alcohol (1/2)
      complex at 52 degrees C also plays an important role.

PMID- 29052489
TI  - Liposomal Hexadecylphosphocholine: Characterization and Effects on Adherent Tumor
      Cells.
AB  - We describe the preparation of small unilamellar and multilamellar vesicles from
      hexadecylphosphocholine, cholesterol and 1,2-dipalmitoyl-sn-glycero
      phosphoglycerol in the molar ratio 4/5/1. Particle size and chemical stability of
      two types of liposomes, small unilamellar vesicles and lyophilized, freshly
      resuspended multilamellar vesicles were proved to be stable for at least 12
      months. Compared to hexadecylphosphocholine in free form, liposomal
      hexadecylphosphocholine showed remarkably reduced hemolysis which did not change
      during storage. Fluorescence microscopy showed the uptake of propidium iodide
      containing hexadecylphosphocholine liposomes by KB and MDA-MB 231 tumor cells.
      Free propidium iodide was not incorporated into these cells. Although
      cytotoxicity seemed to be reduced in liposomal preparations,
      hexadecylphosphocholine liposomes still affected cultured tumor cells to a great
      extent. In relatively low concentrations they induced shape alteration, smoothing
      of the cell surface and blebbing.

PMID- 29052490
TI  - Induction of alloreactive cytotoxic T lymphocytes by intra-splenic immunization
      with allogeneic class I Major Histocompatibility Complex DNA and DC-chol cationic
      liposomes.
AB  - A simple strategy for designing a cancer immunotherapeutic system involves
      modification of tumor cells from tumor-bearing animals in vivo in such a way that
      the host can evoke a specific immune response against them. We have expressed
      allogeneic class I major histocompatibility complex (MHC) molecules on tumor
      cells, through ex vivo DNA-mediated gene transfer. These molecules are potent
      immuno-modulators for the stimulation of strong immune reactions against certain
      malignancies. In order to achieve efficient gene delivery to tumor cells in vivo
      we have compared the efficiencies of gene transfer into mammalian tumor cells by
      the biolistic particle delivery system and cationic liposomes. In this report, we
      have demonstrated that cationic liposomes prepared by DC-chol and DOPE gives the
      best efficiency of transfection for tumor cells in vivo. We also showed that a
      strong anti-H-2Kb allo-reactive cytotoxic T lymphocyte (CTL) response could be
      generated following in vivo immunization of AKR/J mouse spleens with the H-2Kb
      gene and DC-chol cationic liposomes. The direct immunization of mouse spleens to
      induce cell-mediated immunity against exogenous antigens may allow alternative
      treatment strategies for cancer immunotherapy.

PMID- 29052491
TI  - An assessment of the acute dietary exposure to glyphosate using deterministic and
      probabilistic methods.
AB  - Use of glyphosate in crop production can lead to residues of the active substance
      and related metabolites in food. Glyphosate has never been considered acutely
      toxic; however, in 2015 the European Food Safety Authority (EFSA) proposed an
      acute reference dose (ARfD). This differs from the Joint FAO/WHO Meeting on
      Pesticide Residues (JMPR) who in 2016, in line with their existing position,
      concluded that an ARfD was not necessary for glyphosate. This paper makes a
      comprehensive assessment of short-term dietary exposure to glyphosate from
      potentially treated crops grown in the EU and imported third-country food
      sources. European Union and global deterministic models were used to make
      estimates of short-term dietary exposure (generally defined as up to 24 h).
      Estimates were refined using food-processing information, residues monitoring
      data, national dietary exposure models, and basic probabilistic approaches to
      estimating dietary exposure. Calculated exposures levels were compared to the
      ARfD, considered to be the amount of a substance that can be consumed in a single
      meal, or 24-h period, without appreciable health risk. Acute dietary intakes were
      <100% of the ARfD for all foodstuffs, except wild fungi, when calculated using
      the EFSA model. The model assumptions differ from those of the source model
      (German national model), resulting in the use of a higher variability factor.
      Intakes estimated with the German model represented only 18% of the ARfD. The
      impact of differing assumptions regarding variability and other input parameters
      is discussed. Probabilistic exposure estimates showed that the acute intake on no
      person-days exceeded 10% of the ARfD, even for the pessimistic scenario.

PMID- 29052492
TI  - Systematic review and meta-analysis of secondary prophylaxis for prevention of
      HIV-related toxoplasmic encephalitis relapse using trimethoprim-sulfamethoxazole.
AB  - A recent systematic literature and meta-analysis reported relative efficacy of
      trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic
      encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during
      secondary prophylaxis with TMP-SMX, and further explored differences in relapse
      rates prior to introduction of highly active antiretroviral therapy (HAART) and
      the widespread adoption of HAART. A systematic search of PubMed, Embase, and
      Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663
      were excluded after abstract screening, and 38 were excluded after full review
      leaving 6 studies for extraction. We performed double data extraction with a
      third-party adjudicator. Study designs varied with only one randomized study,
      four prospective cohorts and one retrospective cohort. Relapse rates were
      transformed using the Freeman-Tukey method and pooled using both fixed-effect and
      random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI =
      6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART
      studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI
      = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of
      19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates
      between pre- and post-HAART studies were contrary to what might be expected based
      on known benefits of HAART therapy in this population. Nevertheless, cautious
      interpretation is necessary considering the heterogeneity of the included studies
      and a limited number of subjects receiving TMP-SMX reported in the post-HAART
      era.

PMID- 29052493
TI  - Impaired liver cytochrome P450 2C11 activity after dual antiplatelet therapy with
      aspirin and clopidogrel in rats.
AB  - 1. Aspirin (ASA) and clopidogrel (CLP) are used in combination as dual
      antiplatelet therapy (DAPT) for acute coronary syndrome based on their
      complementary mechanisms for platelet aggregation inhibition. However, the
      pharmacokinetics of such drug combination usage has not been thoroughly
      investigated. 2. In the current study, an LC-MS/MS method was developed to
      simultaneously determine the plasma concentrations of ASA and its metabolite
      salicylic acid (SA) with CLP and its metabolites, clopidogrel carboxylic acid
      (CLPM) and clopidogrel active metabolite derivative (CAMD). The pharmacokinetics
      of ASA, SA, CLP, CLPM and CAMD in rats receiving two-week DAPT with ASA and CLP
      were then determined. 3. After two-week DAPT with ASA and CLP in rats, the
      activities of aspirin esterase and rCyp2c11, enzymes mediating rat metabolism of
      ASA and CLP, respectively, in prepared rat liver microsomes were measured
      followed by further determination of rCyp2c11 mRNA expressions. The results
      demonstrated that DAPT led to minimal impact on aspirin esterase activity but
      significant decrease in rCyp2c11 activity and mRNA expression. 4. In conclusion,
      our findings on impairment in rCyp2C11 activity and mRNA expression by DAPT in
      rats could provide guidance on its safe clinical use with other CYP 2C19
      substrates.

PMID- 29052494
TI  - Occurrence of toluene in Canadian total diet foods and its significance to
      overall human exposure.
AB  - Levels of most VOCs in foods are usually low because of their volatility, and
      human exposure to VOCs is expected to be mainly via inhalation of ambient and
      indoor air. However, dietary exposures to VOCs can be significant to overall
      exposures if elevated concentrations of VOCs are present in foods consumed in
      high amounts and/or on a regular basis, and this was demonstrated in this study
      with the occurrence data of toluene from the recent 2014 Canadian Total Diet
      Study (TDS). Concentrations of toluene in the composite samples of most food
      types from the 2014 TDS are low and similar to the results from the previous 2007
      TDS with some exceptions, such as beef steak (670 ng/g (2014 TDS) vs. 14 ng/g
      (2007 TDS)), poultry, chicken and turkey (307 ng/g (2014 TDS) vs. 8.8 ng/g (2007
      TDS)). Toluene concentrations in most of the grain-based and fast food composite
      samples from the 2014 TDS are considerably higher than those from the 2007 TDS,
      with the highest level of 4655 ng/g found in the composite sample of crackers
      from the 2014 TDS (compared to 18 ng/g from 2007 TDS). Dietary exposure estimates
      for toluene based on the occurrence results from the 2014 TDS show that for most
      of the age groups, grain-based foods are the primary source, accounting for an
      average of 77.5% of the overall toluene intake from the diet. The highest dietary
      exposures to toluene were observed for the adult age groups, with estimated
      average exposures ranging from 177.4 to 184.5 ug/d. Dietary exposure estimates to
      toluene are well below oral doses associated with toxicological effects and also
      below the maximum estimated intake (819 ug/d) from air inhalation for adult group
      (20 - 70 years) based on the results from CEPA (Canadian Environmental Protection
      Act) assessment in 1992.

PMID- 29052496
TI  - EDITORIAL.

PMID- 29052495
TI  - Does Metabolic Syndrome or its Individual Components Affect Pain and Function in
      Knee Osteoarthritis Women?
AB  - BACKGROUND: Current studies and research support the role of metabolic syndrome
      (MetS) in knee osteoarthritis (OA). However, few studies have focused on its
      impact on knee OA parameters. The aim of this study was to investigate if
      metabolic syndrome or its individual components affect the intensity of pain,
      functional disability, and radiographic severity in knee osteoarthritis women.
      MATERIALS AND METHODS: We conducted a cross sectional study including confirmed
      radiographic knee osteoarthritis according to Kellgren and Lawrence scale, with
      and without metabolic syndrome according to the National Cholesterol Education
      Program Adult Treatment Panel III criteria. The two groups were compared for pain
      Visual Analogue Scale (VAS), Lequesne index, Womac function, and radiological
      grade after adjusting for significant covariates. Multiple regression analysis
      was used to identify the independent effects of each specific component for
      metabolic syndrome on knee osteoarthritis parameters. RESULTS: One hundred thirty
      women were included. The mean age was 56.68 +/-8.07 [34-75] years, and the mean
      BMI was 32.54+/-2.92 [23-37] kg/m2. The prevalence of metabolic syndrome was
      48.5%. Women with and without metabolic syndrome had similar knee osteoarthritis
      parameters. However, accumulation of MetS components was associated with higher
      level of pain (OR = 3.7, CI = [1.5-5.9], p=0.001), independently of age and BMI.
      Multiple regression analyses showed, after adjusting for all covariates, that
      hyperglycemia had a positive impact on pain (p=0.009), waist circumference was
      positively associated with Lequesne index (p=0.04), high triglycerides level was
      significantly associated with increased pain (p=0.04) and higher Lequesne score
      (p=0.05), and Systolic blood pressure was positively correlated with Lequesne
      index (p=0.01). CONCLUSION: In addition to weight reduction, appropriate
      treatment of metabolic syndrome needs to become an important management strategy
      for knee pain and functional impairment.

PMID- 29052497
TI  - Meloxicam-loaded Phospholipid/solutol(r) HS15 Based Mixed Nanomicelles:
      Preparation, Characterization, and in vitro Antioxidant Activity.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a debilitating disease which results in
      joint destruction, mainly due to chronic inflammation and oxidative stress.
      Meloxicam (MLX) is a preferential cyclooxygenase-2 (COX-2) inhibitor with
      potential free radical scavenging activity. Mixed nanomicelles (NMs) of MLX can
      augment its antioxidant effects. OBJECTIVE: The present study aims to prepare,
      characterize, and evaluate the in vitro antioxidant effects of MLX-loaded mixed
      nanomicelles (MLXNMs). METHOD: Conventional thin-film hydration method was
      employed to fabricate MLX-NMs. The formulations were characterized for particle
      size, zeta potential, entrapment efficiency (EE), and drug loading (DL).
      Additionally, the optimized formulation was characterized for small-angle neutron
      scattering (SANS), in vitro drug release, and morphology. MLX encapsulation in
      NMs was confirmed by Fourier Transform Infrared spectroscopy (FTIR), differential
      scanning calorimetry (DSC), 1H nuclear magnetic resonance (NMR), and X-ray
      diffraction (XRD), studies. The cell uptake of sulforhodamine B (SRB)- labeled
      NMs was studied in RAW 264.7 cells. The in vitro antioxidant activity of
      optimized MLX-NMs was studied by different antioxidant assays. RESULTS: The
      optimized MLX-NMs exhibited average size and zeta potential of 88 +/- 42 nm and 
      47.4 +/- 16.2 mV, respectively. The EE and DL of MLX were 94.13 +/- 1.01 % and
      4.20 +/- 0.05 %, respectively. Morphology studies confirmed the oblate
      ellipsoidal shape of MLXNMs. The in vitro release study exhibited a biphasic
      release pattern. MLX encapsulation into the micelle core was confirmed by FTIR,
      DSC, 1H NMR, and XRD studies. Additionally, SRB-labeled NMs demonstrated
      efficient in vitro cell uptake in RAW 264.7 cells. Furthermore, in vitro
      antioxidant studies exhibited superior free radical scavenging activity of MLXNMs
      as compared to free MLX. CONCLUSION: The NMs potentiate the in vitro antioxidant
      effects of MLX.

PMID- 29052498
TI  - Fabrication & Characterization of 3D Electrospun Biodegradable Nanofibers for
      Wound Dressing, Drug Delivery and Other Tissue Engineering Applications.
AB  - BACKGROUND: The use of electrospinning technology (ET) in fabrication of
      threedimensional biodegradable electrospun nanofibers scaffolds (BENS) has
      recently gained considerable attention in tissue engineering. BENS are superior
      to other existing scaffolds in tissue regeneration as they provide high surface
      area-to-volume ratio, possess high porosity, and offer a biomimetic environment
      in a nanometer scale. OBJECTIVES: To fabricate & characterize BENS using Poly
      (ethylene glycol) (PEG35000) as a biodegradable polymer loaded with Amoxicillin
      Trihydrate (AMX) for use as a wound dressing. METHOD: Solutions of PEG35000 in
      chloroform of varying concentrations were used to fabricate BENS using ET. Blank
      & 1% w/v AMX-loaded BENS were fabricated & characterized. Morphology of BENS were
      assessed using Scanning Electron Microscopy (SEM). Fourier Transform Infrared (FT
      IR) Spectroscopy was used to identify the interaction between PEG35000 and AMX.
      Differential Scanning Calorimetry (DSC) was used to assess the crystallinity and
      thermal behavior of the prepared BENS. The X-Ray Diffraction (XRD) analysis for
      the blank and drug loaded electrospun fibers was carried out to identify the
      changes in their crystalline pattern. The in vitro antibacterial activity against
      common skin Gram-negative and Gram-positive pathogens was also tested. RESULTS:
      Blank & AMX loaded 35% w/v PEG35000 solutions produced the most homogenous and
      intact nanofibers. Major bands of AMX in FTIR were clearly observed in the
      spectrum of AMX with PEG35000 post electrospinning. Moreover, DSC thermograms
      indicated that AMX existed in its amorphous dispersed state within PEG fibers
      supported by the disappearance of its melting peak at 190 degrees C and confirmed
      by the complete absence of AMX crystals under SEM. Finally, the results of DSC
      were confirmed by XRD patterns. Characterizing XRD peaks of AMX loaded with
      PEG3500 post electrospinning disappeared as an indication of the complete
      dispersion of AMX in the loaded fibers and its complete conversion to the
      amorphous form. The in vitro antibacterial assay confirmed the efficiency of the
      drug loaded fibers against the common skin pathogens. CONCLUSION: BENS using
      PEG35000 loaded with AMX were successfully fabricated and characterized. Our
      findings show that PEG BENS has features that make it a promising candidate for
      wound healing applications.

PMID- 29052499
TI  - Experimental Studies on the Systemic Toxicity and Biodistribution of Synthesized
      Calcium Phosphate Nanoparticles After Oral Administration in Rats.
AB  - BACKGROUND AND OBJECTIVE: Nanoparticles have special properties, such as higher
      surface-to-volume ratio and higher reactivity, which increases cell penetrability
      and enhance their applicability in the field of medicine, especially in the case
      where other drugs are ineffective. Calcium phosphate nanoparticles (CPNP) and
      their encapsulation with therapeutic and/or diagnostic agents is such an agent
      synthesized. However, there are concerns related to the colloidal stability of
      these nanoparticles, which are reflected in their tendency to form aggregates in
      the physiological milieu. Therefore, successful translation of these
      nanoparticles from laboratory to the clinic requires studies of biodistribution
      and biocompatibility of nanoparticles for in vivo biomedical applications.
      METHOD: Calcium phosphate nanoparticles synthesized and were tagged with a
      fluorophore and surface stabilized with trisilanol for stable aqueous dispersion.
      The in vivo biodistribution and sub-acute toxicological studies were done for
      orally-administered calcium phosphate nanoparticles. RESULTS: The biodistribution
      studies indicated that these nanoparticles were not prone to rapid degradation or
      excretion in the body, were long-circulating, and could appreciably permeate to
      the brain. Body/organ weight and biochemical analyses did not reveal much
      difference between nanoparticle-administered and saline-administered (control)
      groups. Finally, histopathological analyses of major organs such as liver, lungs,
      heart, stomach and kidney, did not reveal significant abnormalities in the
      treatment groups. CONCLUSION: Thus, it is evident from these sub-acute toxicity
      studies that the nanoparticles appear to be non-toxic to rats following oral
      administration. These observations can have significant implications in calcium
      phosphate nanoparticle-mediated non-toxic drug delivery to target organs, such as
      brain, via non-invasive, oral route.

PMID- 29052500
TI  - Development and Comparison of Nanosponge and Niosome based Gel for the Topical
      Delivery of Tazarotene.
AB  - BACKGROUND: Tazarotene is used as topical retinoid for the treatment of acne,
      psoriasis and sun damaged skin. But its topical formulation has many side-effects
      including itching, burning, dryness, redness, stinging, rash blistering, skin
      discolouration, peeling at the site of application and low bioavailability.
      OBJECTIVE: The present study focuses on the reduction of side effects and
      enhancement of solubility and topical bioavailability of tazarotene by
      formulating nanosponge and niosomes based gel for topical application.
      METHODOLOGY: Nanosponge and niosomes of tazarotene were prepared by emulsion
      solvent evaporation technique and thin film hydration method respectively. The
      prepared formulations were characterized for drug content, morphology, size
      distribution, PDI, viscosity, % swelling and in vitro permeation. The nanosponge
      and niosome formulations were incorporated into carbomer 940 (gel matrix) to
      convert them into nanosponge and niosome based gel. The gel formulations were
      subjected to drug content determination, pH determination, spreadability,
      viscosity, rheological behaviour and in vitro permeation studies using wistar rat
      skin by Franz diffusion cell for optimization. The optimized nanosponge (NSG1)
      containing ethyl cellulose, PVA and dichloromethane and optimized niosomes (NMG5)
      containing tween 20, cholesterol, chlororform were formulated into gels and
      compared with nanosponge (NS1), niosomes (NM5), plain drug gel and marketed
      formulation (Tazaorac) for skin permeation and retention characteristics.
      RESULTS: The nanosponge (NSG1) and niosome (NMG5) gel formulations had lower
      cumulative amount of drug permeated, flux, enhancement ratio and higher skin
      retention within the skin layers and local accumulation efficiency (LAE) than
      plain drug gel and marketed formulation. CONCLUSION: Thus, the study showed that
      nanosponge and niosome based gel formulation can be a possible alternative to
      conventional formulations of tazarotene with enhanced bioavailability and skin
      retention characteristics for topical application.

PMID- 29052502
TI  - Pharmaceutical Nanotechnology United States Patent Watch (April - June 2016).

PMID- 29052501
TI  - Nanoemulsion for Migraine Prophylaxis Nasal Drug Delivery: Preparation,
      Characterization and in vitro Evaluation.
AB  - BACKGROUND: Flunarizine dihydrochloride is used as a prophylaxis to migraine.
      Flunarizine dihydrochloride nanoemulsion was fabricated in this research work.
      Since, it is a low soluble high permeable drug, work was designed to enhance the
      solubility and the same can be administered as nasal drug delivery for faster
      onset of action and therapeutic effect. OBJECTIVE: To fabricate a nanoemulsion of
      flunarizine dihydrochloride by using surfactant and co-surfactants. METHODS: The
      experimental work involved compatibility studies by using FTIR, crystallinity
      study by XRD. The prepared nanoemulsion was studied by photon correlation
      spectroscopy by master sizer 2000 for the particle size analysis and
      characterized for D10, D50 and D90 MPS, span and uniformity. Further studies were
      conducted by Laser light scattering technique by delsa nano common and TEM.
      RESULTS: The study demonstrated that the formulations (FNE 1 -FNE 5) demonstrated
      the MPS of 14, 22.7, 326.7, 14.3 and 40.73 respectively. The formulae FNE1 and
      FNE5 demonstrated the MPS of 214.6+/-179.9 and 2118.6 +/-1503.6 with the diameter
      of 127.8 and 1307, respectively. The zeta potential of FNE1 was -3.84 mV and
      other parameters such as TEM and drug release studies were also reported.
      CONCLUSION: The nanoemulsion of Flunarizine dihydrochloride was prepared
      successfully by using cremophor and labrafil which was better than the existed
      formula prepared by tween 80. The optimised formula demonstrated lower droplet
      size, satisfactory zeta potential, and high drug loading reproducible drug
      release profile.

PMID- 29052503
TI  - Intensive follow-up for women with breast cancer: review of clinical, economic
      and patient's preference domains through evidence to decision framework.
AB  - BACKGROUND: Women treated for breast cancer are followed-up for monitoring of
      treatment effectiveness and for detecting recurrences at an early stage. The type
      of follow-up received may affect women's reassurance and impact on their quality
      of life. Anxiety and depression among women with breast cancer has been
      described, but little is known about how the intensity of the follow-up can
      affect women's psychological status. This study was undertaken to evaluate the
      effects of intensive vs. less-intensive follow-up on different health outcomes,
      to determine what are women's preferences and values regarding the follow-up
      received, and also assess the costs of these different types of follow-up.
      METHODS: A systematic review following standard Cochrane Collaboration methods
      was carried out to assess the efficacy of intensive follow-up versus non
      intensive follow-up in breast cancer patients. Two additional reviews on women's
      preferences and economic evidence were also carried out. The search was performed
      up to January 2016 in: MEDLINE, EMBASE, PDQ, McMaster Health Systems Evidence,
      CENTRAL, and NHS EED (through The Cochrane Library). The quality of evidence was
      assessed by GRADE (for quantitative studies) and CerQUAL (for qualitative
      studies). Several outcomes including mortality, breast cancer recurrences,
      quality of life, and patient satisfaction were evaluated. RESULTS: Six randomised
      trials (corresponding to 3534 women) were included for the evaluation of health
      outcomes; three studies were included for women's values and preferences and four
      for an economic assessment. There is moderate certainty of evidence showing that
      intensive follow-up, including more frequent diagnostic tests or visits, does not
      have effects on 5- or 10-year overall mortality and recurrences in women with
      breast cancer, compared with less intensive follow-up. Regarding women's
      preferences and values, there was important variability among studies and within
      studies (low confidence due to risk of bias and inconsistency). Furthermore,
      intensive follow-up, as opposed to less intensive follow-up, is not likely to be
      cost-effective. CONCLUSIONS: Less intensive follow-up appears to be justified and
      can be recommended over intensive follow-up. Resources could thus be mobilised to
      other aspects of breast cancer care, or other areas of healthcare.

PMID- 29052504
TI  - Family effects on the rurality of GP's work location: a longitudinal panel study.
AB  - BACKGROUND: Reduced opportunities for children's schooling and spouse's/partner's
      employment are identified internationally as key barriers to general
      practitioners (GPs) working rurally. This paper aims to measure longitudinal
      associations between the rurality of GP work location and having (i) school-aged
      children and (ii) a spouse/partner in the workforce. METHODS: Participants
      included 4377 GPs responding to at least two consecutive annual surveys of the
      Medicine in Australia: Balancing Employment and Life (MABEL) national
      longitudinal study between 2008 and 2014. The main outcome, GP work location, was
      categorised by remoteness and population size. Five sequential binary school-age
      groupings were defined according to whether a GP had no children, only preschool
      children (aged 0-4 years), at least one primary-school child (aged 5-11 years),
      at least one child in secondary school (aged 12-18 years), and all children older
      than secondary school (aged >= 19). Partner in the workforce was defined by
      whether a GP had a partner who was either currently working or looking for work,
      or not. Separate generalised estimating equation models, which aggregated
      consecutive annual observations per GP, tested associations between work location
      and (i) educational stages and (ii) partner employment, after adjusting for key
      covariates. RESULTS: Male GPs with children in secondary school were
      significantly less likely to work rurally (inclusive of > 50 000 regional centres
      through to the smallest rural towns of < 5000) compared to male GPs with children
      in primary school. In contrast, female GPs' locations were not significantly
      associated with the educational stage of their children. Having a partner in the
      workforce was not associated with work location for male GPs, whereas female GPs
      with a partner in the workforce were significantly less likely to work in smaller
      rural/remote communities (< 15 000 population). CONCLUSIONS: This is the first
      systematic, national-level longitudinal study showing that GP work location is
      related to key family needs which differ according to GP gender and educational
      stages of children. Such non-professional factors are likely to be dynamic across
      the GP's lifespan and should be regularly reviewed as part of GP retention
      planning. This research supports investment in regional development for strong
      local secondary school and partner employment opportunities.

PMID- 29052505
TI  - Transcriptome assembly in Suaeda aralocaspica to reveal the distinct temporal
      gene/miRNA alterations between the dimorphic seeds during germination.
AB  - BACKGROUND: Dimorphic seeds from Suaeda aralocaspica exhibit different
      germination behaviors that are thought to be a bet-hedging strategy advantageous
      in harsh and unpredictable environments. To understand the molecular mechanisms
      of Suaeda aralocaspica dimorphic seed germination, we applied RNA sequencing and
      small RNA sequencing for samples collected at three germination stages. RESULTS:
      A total of 79,414 transcripts were assembled using Trinity, of which 57.67% were
      functionally annotated. KEGG enrichment unveiled that photosynthesis and flavonol
      biosynthesis pathways were activated earlier in brown seed compared with black
      seed. Gene expression analysis revealed that nine candidate unigenes in
      gibberellic acid and abscisic acid signal transduction and 23 unigenes in
      circadian rhythm-plant pathway showed distinct expression profiles to promote
      dimorphic seed germination. 194 conserved miRNAs comprising 40 families and 21
      novel miRNAs belonging to 20 families in Suaeda aralocaspica were identified
      using miRDeep-P and Mfold. The expression of miRNAs in black seed was suppressed
      at imbibition stage. Among the identified miRNAs, 59 conserved and 13 novel
      miRNAs differentially expressed during seed germination. Of which, 43 conserved
      and nine novel miRNAs showed distinct expression patterns between black and brown
      seed. Using TAPIR, 208 unigenes were predicted as putative targets of 35
      conserved miRNA families and 17 novel miRNA families. Among functionally
      annotated targets, genes participated in transcription regulation constituted the
      dominant category, followed by genes involved in signaling and stress response.
      Seven of the predicted targets were validated using 5' rapid amplification of
      cDNA ends or real-time quantitative reverse transcription-PCR. CONCLUSIONS: Our
      results indicate that specific genes and miRNAs are regulated differently between
      black and brown seed during germination, which may contribute to the different
      germination behaviors of Suaeda aralocaspica dimorphic seeds in unpredictable
      variable environments. Our results lay a solid foundation for further studying
      the roles of candidate genes and miRNAs in Suaeda aralocaspica dimorphic seed
      germination.

PMID- 29052506
TI  - The proposed new species, cacao red vein virus, and three previously recognized
      badnavirus species are associated with cacao swollen shoot disease.
AB  - BACKGROUND: Cacao swollen shoot virus (CSSV), Cacao swollen shoot CD virus
      (CSSCDV), and Cacao swollen shoot Togo A virus (CSSTAV) cause cacao swollen shoot
      disease (CSSD) in West Africa. During 2000-2003, leaf and shoot-swelling symptoms
      and rapid tree death were observed in cacao in Cote d'Ivoire and Ghana. Molecular
      tests showed positive infection in only ~50-60% of symptomatic trees, suggesting
      the possible emergence of an unknown badnavirus. METHODS: The DNA virome was
      determined from symptomatic cacao samples using Illumina-Hi Seq, and sequence
      accuracy was verified by Sanger sequencing. The resultant 14, and seven
      previously known, full-length badnaviral genomic and RT-RNase H sequences were
      analyzed by pairwise distance analysis to resolve species relationships, and by
      Maximum likelihood (ML) to reconstruct phylogenetic relationships. The viral
      coding and non-coding sequences, genome organization, and predicted conserved
      protein domains (CPDs) were identified and characterized at the species level.
      RESULTS: The 21 CSSD-badnaviral genomes and RT-RNase H sequences shared 70-100%
      and 72-100% identity, respectively. The RT-RNase H analysis predicted four
      species, based on an >=80% species cutoff. The ML genome sequence tree resolved
      three well-supported clades, with >=70% bootstrap, whereas, the RT-RNase H
      phylogeny was poorly resolved, however, both trees grouped CSSD isolates within
      one large clade, including the newly discovered Cacao red vein virus (CRVV)
      proposed species. The genome arrangement of the four species consists of four,
      five, or six predicted open reading frames (ORFs), and the CPDs have similar
      architectures. By comparison, two New World cacao-infecting badnaviruses encode
      four ORFs, and harbor CPDs like the West African species. CONCLUSIONS: Three
      previously recognized West African cacao-infecting badnaviral species were
      identified, and a fourth, previously unidentified species, CRVV, is described for
      the first time. The CRVV is a suspect causal agent of the rapid decline
      phenotype, however Koch's Postulates have not been proven. To reconcile viral
      evolutionary with epidemiology considerations, more detailed information about
      CSSD-genomic variability is essential. Also, the functional basis for the
      multiple genome arrangements and subtly distinct CPD architectures among cacao
      infecting badnaviruses is poorly understood. New knowledge about functional
      relationships may help explain the diverse symptomatologies observed in affected
      cacao trees.

PMID- 29052507
TI  - Metabolic shift in density-dependent stem cell differentiation.
AB  - BACKGROUND: Vascular progenitor cells (VPCs) derived from embryonic stem cells
      (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies.
      During the optimization of endothelial cell (EC) inductions from mouse ESCs using
      our staged and chemically-defined induction methods, we found that cell seeding
      density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant
      variable directing ESCs into FLK1+ VPCs during stage 1 induction. Here, we
      examine potential contributions from cell-to-cell signaling or cellular
      metabolism in the production of VPCs from ESCs seeded at different cell
      densities. METHODS: Using 1D 1H-NMR spectroscopy, transcriptomic arrays, and flow
      cytometry, we observed that the density-dependent differentiation of ESCs into
      FLK1+ VPCs positively correlated with a shift in metabolism and cellular growth.
      RESULTS: Specifically, cell differentiation correlated with an earlier plateauing
      of exhaustive glycolysis, decreased lactate production, lower metabolite
      consumption, decreased cellular proliferation and an increase in cell size. In
      contrast, cells seeded at a lower density of 1,000 cells/cm2 exhibited increased
      rates of glycolysis, lactate secretion, metabolite utilization, and proliferation
      over the same induction period. Gene expression analysis indicated that high cell
      seeding density correlated with up-regulation of several genes including cell
      adhesion molecules of the notch family (NOTCH1 and NOTCH4) and cadherin family
      (CDH5) related to vascular development. CONCLUSIONS: These results confirm that a
      distinct metabolic phenotype correlates with cell differentiation of VPCs.

PMID- 29052508
TI  - Assessment of the clinical efficacy of cell-assisted lipotransfer and
      conventional fat graft: a meta-analysis based on case-control studies.
AB  - BACKGROUND: Cell-assisted lipotransfer is a novel technique for fat grafting.
      This study aimed to investigate the clinical efficacy of cell-assisted
      lipotransfer technology compared with conventional fat grafting. METHODS:
      According to PRISMA guidelines, related articles in PubMed, Embase and Cochrane
      library were systematically searched. Studies focusing on fat survival rate
      and/or patient satisfaction rate for fat grafting alone versus cell-assisted
      lipotransfer were retrieved. Estimated fat survival and patient satisfaction
      rates were pooled. Subgroup analysis was stratified by the transplant site.
      Publication bias was conducted. Furthermore, the stability of results was
      assessed by sensitivity analysis. RESULTS: Nine articles were included in the
      meta-analysis. Significant heterogeneity was observed among individual studies
      for fat survival rate assessment (I 2 = 98.3%, P < 0.001). The fat survival rate
      was significantly higher in the cell-assisted lipotransfer group than in the
      control group [weighted mean difference = 25.85, 95% confidence interval 5.39
      46.31; P = 0.013]. Notably, results remained unchanged in the sensitivity
      analyses. No significant difference was found in the patient satisfaction rate
      between the cell-assisted lipotransfer and control groups [odds ratio = 3.69, 95%
      confidence interval 0.73-18.53; P = 0.113]. In subgroup analysis, a significantly
      higher patient satisfaction rate was found in cell-assisted lipotransfer fat
      graft group in the face (odds ratio = 18.85, 95% confidence interval 9.03, 28.68;
      P < 0.001) and arm (odds ratio = 64.60, 95% confidence interval 58.79, 70.41; P <
      0.001) than in the controls. Finally, no significant publication bias was found
      (P = 0.371). CONCLUSION: This study suggests that cell-assisted lipotransfer is
      superior to conventional lipoinjection with improved fat survival rate. However,
      the long-term efficacy should be evaluated in further studies.

PMID- 29052509
TI  - A Yin-Yang 1/miR-30a regulatory circuit modulates autophagy in pancreatic cancer
      cells.
AB  - BACKGROUND: Autophagy is a highly regulated biological process that mediates the
      degradation of intracellular components. It is required for tumor cell metabolism
      and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy
      in several carcinomas. However, its role in autophagy in pancreatic cancer, one
      of the deadliest human malignancies, is unknown. Here, we investigated the
      function of YY1 in pancreatic cancer cells autophagy and its mechanisms of
      action. METHODS: The activity of cells undergoing autophagy was assessed using
      transmission electron microscopy, immunofluorescence, and Western blotting. A
      luciferase activity assay, real-time quantitative polymerase chain reaction (RT
      qPCR), and chromatin immunoprecipitation (ChIP) were also used to identify
      putative downstream targets of YY1. RESULTS: YY1 was confirmed to regulate
      autophagy in pancreatic cancer cells. It was found to directly regulate the
      expression of miR-30a, a known modulator of autophagy-associated genes.
      Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of
      YY1. CONCLUSIONS: Cumulatively, our data suggest that miR-30a acts in a feedback
      loop to modulate the pro-autophagic activities of YY1. Thus, autophagy in
      pancreatic cancer cells may be regulated, in part, by a tightly coordinated
      YY1/miR-30a regulatory circuit. These findings provide a potential druggable
      target for the development of treatments for pancreatic cancer.

PMID- 29052510
TI  - Validity and reliability of a Nigerian-Yoruba version of the stroke-specific
      quality of life scale 2.0.
AB  - BACKGROUND: Psychometric evidence is necessary to establish scientific integrity
      and clinical usefulness of translations and cultural adaptations of the Stroke
      Specific Quality of Life (SS-QoL) scale. However, the limited evidence on
      psychometrics of Yoruba version of SS-QoL 2.0 (SS-QoL(Y)) is a significant
      shortcoming. This study assessed the test-retest reliability, internal
      consistency, convergent, divergent, discriminant and known-group validity of the
      SS-QoL(Y). METHODS: Yoruba version of the WHOQoL-BREF was used to test the
      convergent and divergent validity of the SS-QoL(Y) among 100 consenting stroke
      survivors. The WHOQoL-BREF and SS-QoL(Y) was administered randomly in order to
      eliminate bias. The test-retest reliability of the SS-QoL(Y) was carried out
      among 68 of the respondents within an interval of 7 days. All respondents were
      purposively recruited from selected secondary and tertiary health facilities in
      South-west Nigeria. Data were analysed using descriptive statistics of mean and
      standard deviation, and inferential statistics of Spearman correlation,
      Cronbach's alpha, Intra-class Correlation Coefficient (ICC), Independent t-test
      and One-way ANOVA. Alpha level was set at p < 0.05. RESULT: The physical health,
      psychological health, social relationship and environment domains on WHOQoL-BREF
      with correlation coefficient that ranged from 0.214 to 0.360 showed significant
      correlation with similar domains on SS-QoL(Y). Dissimilar domains between the two
      scales had r values from 0.035 to 0.366. Discriminant validity of SS-QoL(Y)
      showed that items' r value ranged from 0.711 to 0.920 with their hypothesized
      domains. The scale demonstrated moderate to strong test-retest reliability with
      Intra-class correlation coefficient (ICC) for the domains and overall scores (r =
      0.47 to 0.81) and moderate to high internal consistency (Cronbach's alpha =0.61
      to 0.82) for domains scores. These correlations were also significant for the
      domains and overall scores (p < 0.05). There were no significant differences
      across different age groups or gender for the domains or overall scores of SS
      QoL(Y). CONCLUSIONS: Discriminant and known-group validity, test-retest
      reliability and internal consistency of the Yoruba version of the Stroke Specific
      Quality of Life 2.0 are adequate while the convergent and divergent validity are
      low but acceptable. The SS-QoL(Y) is recommended for assessing health-related
      quality of life among Yoruba stroke survivors.

PMID- 29052511
TI  - Q&A: What are pathogens, and what have they done to and for us?
AB  - Microbes are found on us, within us and around us. They inhabit virtually every
      environment on the planet and the bacteria carried by an average human, mostly in
      their gut, outnumber human cells. The vast majority of microbes are harmless to
      us, and many play essential roles in plant, animal and human health. Others,
      however, are either obligate or facultative pathogens exerting a spectrum of
      deleterious effects on their hosts. Infectious diseases have historically
      represented the most common cause of death in humans until recently, exceeding by
      far the toll taken by wars or famines. From the dawn of humanity and throughout
      history, infectious diseases have shaped human evolution, demography, migrations
      and history.

PMID- 29052512
TI  - Voluntarily stopping eating and drinking (VSED) to hasten death: may clinicians
      legally support patients to VSED?
AB  - Jox and colleagues recently compared and contrasted two leading end-of-life exit
      options, namely voluntarily stopping eating and drinking (VSED) and medical aid
      in dying (MAID). The authors argue that policymakers and medical societies should
      consider VSED and MAID in a uniform and consistent manner given that clinician
      participation in both constitutes assisted suicide. This is a very controversial
      topic. Herein, it is questioned whether there really is disparate consideration
      of VSED and MAID and whether it is justified, bearing in mind that VSED is not
      assisted suicide.Please see related article:
      http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0950-1 .

PMID- 29052513
TI  - A method to reduce ancestry related germline false positives in tumor only
      somatic variant calling.
AB  - BACKGROUND: Significant clinical and research applications are driving large
      scale adoption of individualized tumor sequencing in cancer in order to identify
      tumors-specific mutations. When a matched germline sample is available, somatic
      mutations may be identified using comparative callers. However, matched germline
      samples are frequently not available such as with archival tissues, which makes
      it difficult to distinguish somatic from germline variants. While population
      databases may be used to filter out known germline variants, recent studies have
      shown private germline variants result in an inflated false positive rate in
      unmatched tumor samples, and the number germline false positives in an individual
      may be related to ancestry. METHODS: First, we examined the relationship between
      the germline false positives and ancestry. Then we developed and implemented a
      tumor only caller (LumosVar) that leverages differences in allelic frequency
      between somatic and germline variants in impure tumors. We used simulated data to
      systematically examine how copy number alterations, tumor purity, and sequencing
      depth should affect the sensitivity of our caller. Finally, we evaluated the
      caller on real data. RESULTS: We find the germline false-positive rate is
      significantly higher for individuals of non-European Ancestry largely due to the
      limited diversity in public polymorphism databases and due to population-specific
      characteristics such as admixture or recent expansions. Our Bayesian tumor only
      caller (LumosVar) is able to greatly reduce false positives from private germline
      variants, and our sensitivity is similar to predictions based on simulated data.
      CONCLUSIONS: Taken together, our results suggest that studies of individuals of
      non-European ancestry would most benefit from our approach. However, high
      sensitivity requires sufficiently impure tumors and adequate sequencing depth.
      Even in impure tumors, there are copy number alterations that result in germline
      and somatic variants having similar allele frequencies, limiting the sensitivity
      of the approach. We believe our approach could greatly improve the analysis of
      archival samples in a research setting where the normal is not available.

PMID- 29052514
TI  - Five-fraction SBRT for ultra-central NSCLC in-field recurrences following high
      dose conventional radiation.
AB  - PURPOSE/OBJECTIVE: Local treatment options for patients with in-field non-small
      cell lung cancer (NSCLC) recurrence following conventionally fractionated
      external beam radiation therapy (CF-EBRT) are limited. Stereotactic body
      radiation therapy (SBRT) is a promising modality to achieve reasonable local
      control, although toxicity remains a concern. MATERIALS/METHODS: Patients
      previously treated with high-dose CF-EBRT (>=59.4 Gy, <=3 Gy/fraction) for non
      metastatic NSCLC who underwent salvage SBRT for localized ultra-central in-field
      recurrence were included in this analysis. Ultra-central recurrences were defined
      as those abutting the trachea, mainstem bronchus, or esophagus and included both
      parenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate
      local control and overall survival. Durable local control was defined as >=12
      months. Toxicity was scored per the CTC-AE v4.0. RESULTS: Twenty patients were
      treated with five-fraction robotic SBRT for ultra-central in-field recurrence
      following CF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of
      tumors were classified as squamous cell carcinoma. The median interval between
      the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 - 93.6 months). The
      median CF-EBRT dose was 63 Gy (range: 59.4 - 75 Gy), the median SBRT dose was 35
      Gy (range: 25 - 45 Gy), and the median total equivalent dose in 2 Gy fractions
      (EQD2) was 116 Gy (range: 91.3 - 136.7 Gy). At a median follow-up of 12 months
      for all patients and 37.5 months in surviving patients, the majority of patients
      (90%) have died. High-dose SBRT was associated with improved local control (p <
      .01), and the one-year overall survival and local control were 77.8% and 66.7%
      respectively in this sub-group. No late esophageal toxicity was noted, although a
      patient who received an SBRT dose of 45 Gy (total EQD2: 129.7 Gy) experienced
      grade 5 hemoptysis 35 months following treatment. CONCLUSIONS: Although the
      overall prognosis for patients with in-field ultra-central NSCLC recurrences
      following CF-EBRT remains grim, five-fraction SBRT was well tolerated with an
      acceptable toxicity profile. Dose escalation above 35 Gy may offer improved local
      control, however caution is warranted when treating high-risk recurrences with
      aggressive regimens.

PMID- 29052515
TI  - Is there a financial incentive to immigrate? Examining of the health worker
      salary gap between India and popular destination countries.
AB  - BACKGROUND: International migration is one of the factors resulting in the
      shortage of Human Resources for Health (HRH) in India. Literature suggests that
      migration is fuelled by the prospect of higher salaries available abroad. The
      extent of these salary differentials are unknown, and this study seeks to examine
      the salaries of selected HRH in India and four popular destination countries
      (United States of America, United Kingdom, Canada and the United Arab Emirates),
      whilst accounting for the in-country cost of living. This study will therefore
      determine truer financial incentives for Indian HRH to migrate abroad. METHODS: A
      purchasing power parity (PPP) ratio is employed to equalise the international
      price of buying a representative basket of commonly bought goods (including food,
      entertainment, fuel and utilities). Using the PPP index, real differences in
      salaries are directly compared for selected work categories and different levels
      of work experience in the four respective countries. RESULTS: Nurses in the USA
      can earn up to 82.7% more than their Indian counterparts. Nurses in Canada and
      the UAE reveal more modest salary differentials, yet still significant better off
      by up to 28 and 20% respectively. Only nurses in the UK are potentially
      materially worse off than nurses working in India. We observe significant
      potential PPP gains of up to 57.4, 99.1 and 94.4% for medical doctors in the USA,
      Canada and the UAE respectively. Medical specialists potentially experience the
      greatest income disparities with anaesthetists potentially earning up to 600%
      more than their counterparts in India. Radiologists operating in the UK and
      general surgeons working in the USA can potentially earn more than double that of
      their counterparts working in India. We observe more modest positive or
      negligible PPP gains in other selected countries for health specialists.
      CONCLUSION: Even when considering the differences in the cost of living, the
      financial incentive for selected cadres of Indian HRH to seek work abroad remains
      strong. The migration of Indian HRH to countries offering superior salaries makes
      it difficult for India to retain experienced health personal and compromises
      government efforts to render health care more accessible across the country.

PMID- 29052516
TI  - Pure exercise intolerance and ophthalmoplegia associated with the m.12,294G > A
      mutation in the MT-TL2 gene: a case report.
AB  - BACKGROUND: Pure exercise intolerance associated with exclusive affection of
      skeletal muscle is a very rare phenotype of patients with mitochondrial myopathy.
      Moreover, the exercise intolerance in these rare patients is yet not well
      explored, as most of known cases have not been assessed by objective testing, but
      only by interview. We report a patient with a mitochondrial DNA (mtDNA) mutation
      that gives rise to an exclusive myopathy associated with exercise intolerance and
      ophthalmoplegia. We quantified the patient's exercise intolerance through
      detailed exercise testing. CASE PRESENTATION: A 39-year-old man presented with
      exercise intolerance and chronic progressive external ophthalmoplegia. Sequencing
      of the entire mtDNA identified a m.12,294G > A mutation in the MT-TL2 gene. The
      mutation was heteroplasmic in skeletal muscle (75%) while undetectable in blood,
      urinary sediment, and buccal mucosa as well as in tissues from the patient's
      mother. The mutation affected a highly conserved site in the anticodon stem of
      the mitochondrial transfer RNA Leucine (CUN) molecule and lead to a severe
      combined respiratory chain defect. Exercise physiological studies in the patient
      demonstrated a significantly reduced maximal oxygen uptake of 20.4 ml O2 * min-1
      * kg-1 (about half of normal) as well as threefold elevated lactate/pyruvate
      ratios. CONCLUSION: The findings of our study support that the m.12,294G > A
      mutation is pathogenic. Likely, the mutation arose sporadically in early
      embryogenesis after differentiation of the mesoderm into muscle progenitor cells,
      leading to a pure myopathic phenotype.

PMID- 29052517
TI  - Constitutive expression of OsDof4, encoding a C2-C2 zinc finger transcription
      factor, confesses its distinct flowering effects under long- and short-day
      photoperiods in rice (Oryza sativa L.).
AB  - BACKGROUND: Dof (DNA binding with one finger) proteins, a class of plant-specific
      transcription factors which contain a conserved C2-C2-type zinc finger domain,
      are involved in many fundamental processes. In the Arabidopsis photoperiod
      response pathway, CDF (CYCLING DOF FACTOR) proteins have a primary role as acting
      via transcriptional repression of the direct FLOWERING LOCUS T (FT) activator
      CONSTANS (CO). Our previous study indicated that one of CDF homologs, OsDOf12,
      was involved in photoperiodic flowering. However, the functional characterization
      of other rice CDF like genes is still in progress. Here, we characterized the
      function of OsDof4 in rice. RESULTS: Phylogenic analysis indicated that OsDof4 is
      closely clustered into the same subgroup with CDFs and OsDof12. The subcellular
      localization experiment and transcriptional activity assay suggested that OsDof4
      may function as a transcription factor. The diurnal expression pattern indicated
      that OsDof4 was regulated by endogenous circadian clock. Overexpression of OsDof4
      led to earlier flowering under natural long-day field conditions (NLDs) and late
      flowering under natural short-day field conditions (NSDs), respectively. We
      compared the expression level of key floral genes in vector line and OsDof4-ox
      lines grown under long-day conditions (LDs) and short-day conditions (SDs). Real
      time q-PCR results demonstrated that under LDs, Hd3a, RFT1 and Ehd1 were up
      regulated whereas under SDs they were down-regulated. Hd1 was down-regulated at
      dusk period independent of photoperiods. CONCLUSIONS: Taken these results
      together, we may speculate that the abnormal flowering responses in OsDof4-ox
      plants under LDs and SDs might be mediated by Ehd1 and Hd1.

PMID- 29052518
TI  - Voluntary stopping of eating and drinking: is medical support ethically
      justified?
AB  - BACKGROUND: Physician-assisted dying has been the subject of extensive discussion
      and legislative activity both in Europe and North America. In this context, dying
      by voluntary stopping of eating and drinking (VSED) is often proposed, and
      practiced, as an alternative method of self-determined dying, with medical
      support for VSED being regarded as ethically and legally justified. ARGUMENT: In
      our opinion, this view is flawed. First, we argue that VSED falls within the
      concept of suicide, albeit with certain unique features (non-invasiveness,
      initial reversibility, resemblance to the natural dying process). Second, we
      demonstrate, on the basis of paradigmatic clinical cases, that medically
      supported VSED is, at least in some instances, tantamount to assisted suicide.
      This is especially the case if a patient's choice of VSED depends on the
      physician's assurance to provide medical support. CONCLUSION: Thus, for many
      jurisdictions worldwide, medically supported VSED may fall within the legal
      prohibitions on suicide assistance. Physicians, lawmakers, and societies should
      discuss specific ways of regulating medical support for VSED in order to provide
      clear guidance for both patients and healthcare professionals. Please see related
      article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0951-0
      .

PMID- 29052519
TI  - Circuit training enhances function in patients undergoing total knee
      arthroplasty: a retrospective cohort study.
AB  - BACKGROUND: The number of patients receiving total knee arthroplasty (TKA) has
      been rising every year due to the aging population and the obesity epidemic. Post
      operative rehabilitation is important for the outcome of TKA. METHODS: A series
      of 34 patients who underwent primary unilateral TKA was retrospectively collected
      and divided into either exercise group (n = 16) and control group (n = 18). The
      exercise group underwent a 24-week course of circuit training beginning 3 months
      after total knee arthroplasty (TKA). The effect of circuit training on TKA
      patients in terms of motion analysis, muscle strength testing, Knee injury and
      Osteoarthritis Outcomes Score (KOOS) questionnaire and patient-reported outcome
      measurement Short-Form Health Survey (SF-36) at the pre-operation, pre-exercise,
      mid-exercise, and post-exercise. RESULTS: Motion analysis revealed the stride
      length, step velocity, and excursion of active knee range of motion significantly
      improved in the exercise group when compared to those in the control group. KOOS
      questionnaire showed a greater improvement in pain, ADL, and total scores in the
      exercise group. The SF-36 questionnaire revealed a significant improvement in
      general health, bodily pain, social function, and physical components score in
      the exercise group. CONCLUSIONS: The post-operative circuit training intervention
      can facilitate recovery of knee function and decrease the degree of pain in the
      TKA and might be considered a useful adjunct rehabilitative modality. The
      ultimate influence of circuit training on TKA needs further a prospective
      randomized clinical trial study and long-term investigation. TRIAL REGISTRATION:
      NCT02928562.

PMID- 29052520
TI  - Upregulation of DARS2 by HBV promotes hepatocarcinogenesis through the miR-30e
      5p/MAPK/NFAT5 pathway.
AB  - BACKGROUND: Infection with the hepatitis B virus (HBV) is closely associated with
      the development of hepatocellular carcinoma (HCC). The osmoregulatory
      transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown
      to play an important role in the development of many types of human cancers. The
      role of NFAT5 in HBV-associated HCC has never previously been investigated.
      METHODS: We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC
      samples, adjacent nontumor tissues and different hepatoma cell lines by
      quantitative real-time polymerase chain reaction and /or Western blot. Clinical
      data of HCC patients for up to 80 months were analyzed. The regulatory mechanisms
      upstream and convergent downstream pathways of NFAT5 in HBV-associated HCC were
      investigated by ChIP-seq, MSP, luciferase report assay and bioinformation
      anaylsis. RESULTS: We first found that higher levels of NFAT5 expression predict
      a good prognosis, suggesting that NFAT5 is a potential tumor-suppressing gene,
      and verified that NFAT5 promotes hepatoma cell apoptosis and inhibits cell growth
      in vitro. Second, our results showed that HBV could suppress NFAT5 expression by
      inducing hypermethylation of the AP1-binding site in the NFAT5 promoter in
      hepatoma cells. In addition, HBV also inhibited NFAT5 through miR-30e-5p targeted
      MAP4K4, and miR-30e-5p in turn inhibited HBV replication. Finally, we
      demonstrated that NFAT5 suppressed DARS2 by directly binding to its promoter.
      DARS2 was identified as an HCC oncogene that promotes HCC cell cycle progression
      and inhibits HCC cell apoptosis. CONCLUSION: HBV suppresses NFAT5 through the miR
      30e-5p/mitogen-activated protein kinase (MAPK) signaling pathway upstream of
      NFAT5 and inhibits the NFAT5 to enhance HCC tumorigenesis via the downstream
      target genes of DARS2.

PMID- 29052522
TI  - Predictors of diffuse alveolar damage in patients with acute respiratory distress
      syndrome: a retrospective analysis of clinical autopsies.
AB  - BACKGROUND: Although diffuse alveolar damage (DAD) is considered the typical
      histological pattern of acute respiratory distress syndrome (ARDS), only half of
      patients exhibit this morphological hallmark. Patients with DAD may have higher
      mortality than those without DAD. Therefore, we aimed to identify the factors
      associated with DAD in patients with ARDS. METHODS: We analyzed autopsy samples
      of 356 patients who had ARDS at the time of death. DAD was assessed by two
      pathologists, and ARDS criteria were evaluated by two intensivists. Criteria for
      severe ARDS included the degree of hypoxemia and the ancillary variables of the
      current Berlin definition assessed within 48 h before death: radiographic
      severity, high positive end-expiratory pressure (PEEP) level, and physiological
      variables (i.e., altered respiratory system compliance and large anatomic dead
      space). RESULTS: After multivariable analysis, high PEEP levels, physiological
      variables, and opacities involving only three quadrants on chest radiographs were
      not associated with DAD. The four markers independently associated with DAD were
      (1) duration of evolution (OR 3.29 [1.95-5.55] for patients with ARDS >= 3 days,
      p < 0.001), (2) degree of hypoxemia (OR 3.92 [1.48-10.3] for moderate ARDS and
      6.18 [2.34-16.3] for severe ARDS, p < 0.01 for both), (3) increased dynamic
      driving pressure (OR 1.06 [1.04-1.09], p = 0.007), and (4) radiographic severity
      (OR 2.91 [1.47-5.75] for patients with diffuse opacities involving the four
      quadrants, p = 0.002). DAD was found in two-thirds of patients with a ratio of
      partial pressure of arterial oxygen to fraction of inspired oxygen <= 100 mmHg
      and opacities involving the four quadrants. CONCLUSIONS: In addition to severe
      hypoxemia, diffuse opacities involving the four quadrants were a strong marker of
      DAD.

PMID- 29052521
TI  - High seroprevalance of Neospora caninum in dogs in Victoria, Australia, compared
      to 20 years ago.
AB  - BACKGROUND: Canids are definitive hosts of the apicomplexan parasite Neospora
      caninum, the leading cause of abortion in cattle worldwide. For horizontal
      transmission from canids to occur, oocysts of N. caninum must be shed by the
      definitive host into the environment of susceptible intermediate hosts such as
      cattle. The purpose of this study was to determine the prevalence of N. caninum
      in canids in Victoria, Australia's leading dairy producing state. RESULTS:
      Neospora-like oocysts were observed in 8% (18/234) of faecal samples from wild
      dogs, domestic dogs and red foxes from Victoria, Australia. However, none tested
      positive for N. caninum DNA using a quantitative PCR. In a separate sample
      population, blood sera from 483 domestic dogs were tested for anti-N. caninum
      antibodies using competitive ELISA. A subset of cELISA samples were re-tested
      using indirect fluorescence antibody test (IFAT). A seroprevalence of 29.8%
      (144/483; 95% CI: 11.7-47.8%) was calculated when using cELISA; whereas it was
      32.9% (27/80; 95% CI: 15.8-51.8%) using IFAT. Potential risk factors were
      evaluated using univariable analyses and then assessed in separate multivariable
      models. Using 'aged' dogs as a reference, the seroprevalence of 'adolescent' and
      'adult' dogs was 88% (P = 0.05) and 91% (P = 0.08), respectively, indicating
      seroprevalence increases with age. There was a 19% higher likelihood of infection
      in rural locations (P = 0.10) relative to urban areas. Jack Russell Terriers had
      a 22% higher risk of a cELISA-positive result (P = 0.05) regardless of
      geographical location, age or sex. CONCLUSION: These results demonstrate that
      exposure to N. caninum in domestic dogs is widespread in Victoria, although
      faecal oocyst shedding is infrequent. Our results indicate increased N. caninum
      seroprevalance status in dogs over the past two decades. The results imply that
      dogs get either exposed to the infected meat more frequently or that vertical dam
      to foetus transmission is more frequent than previously thought. Our study calls
      for re-evaluation of historical N. caninum seroprevalance studies, because the
      attitude to dog diet changes.

PMID- 29052523
TI  - Longitudinal study of Staphylococcus aureus colonization and infection in a
      cohort of swine veterinarians in the United States.
AB  - BACKGROUND: People working with pigs are at elevated risk of harboring
      methicillin resistant S. aureus (MRSA) in their nose, which is attributable to
      occupational exposure to animals harboring livestock adapted S. aureus. To obtain
      insight into the biological nature of occupationally related nasal culture
      positivity, we conducted a longitudinal study of 66 swine veterinarians in the
      USA. METHODS: The study cohort resided in 15 US states and worked predominantly
      with swine. Monthly for 18 months, participants self-collected nasal swabs and
      completed a survey to report recent exposure to pigs and other animals; the
      occurrence of work related injuries; and any relevant health events such as skin
      and soft tissue infections or confirmed staphylococcal infections. Nasal swabs
      were cultured using selective methods to determine the presence of MRSA and
      methicillin susceptible S. aureus (MSSA), and isolates were characterized by spa
      typing and MLST. RESULTS: Prevalences of S. aureus (64%, monthly range from 58 to
      82%) and MRSA (9.5%; monthly range from 6 to15%) were higher than reported for
      the US population (30% and 1.5% respectively). Predominant spa types were t034
      (ST398, 37%), t002 (ST5, 17%) and t337 (ST9/ST398 13%), a distribution similar to
      that found in a concurrent study in pigs in the USA. Veterinarians were
      classified into three groups: Persistent carriers (PC, 52%), Intermittent
      carriers (IC, 47%) and Non-carriers (NC, 1%). Persistent carriage of a single spa
      type was observed in 14 (21%) of participants, and paired (first and last)
      isolates from PC subjects had minor genetic differences. Swabs from PC
      veterinarians carried higher numbers of S. aureus. Among IC veterinarians,
      culture positivity was significantly associated with recent contact with pigs.
      CONCLUSIONS: Exposure to pigs did not lead to prolonged colonization in most
      subjects, and the higher numbers of S. aureus in PC subjects suggests that
      unknown host factors may determine the likelihood of prolonged colonization by S.
      aureus of livestock origin. Exposure to S. aureus and persistent colonization of
      swine veterinarians was common but rarely associated with S. aureus disease.

PMID- 29052524
TI  - Soluble CD40L is associated with increased oxidative burst and neutrophil
      extracellular trap release in Behcet's disease.
AB  - BACKGROUND: Studies have suggested that soluble factors in plasma from patients
      with active (aBD) and inactive (iBD) Behcet's disease (BD) stimulate neutrophil
      function. Soluble CD40 ligand (sCD40L) is an important mediator of inflammation
      in BD. Its expression and effect on neutrophil oxidative burst and neutrophil
      extracellular trap (NET) release have not been characterized. In this study, we
      sought to investigate the role of plasma and the CD40L pathway on NET release and
      the oxidative burst profile in patients with aBD and iBD. METHODS: Neutrophils
      and peripheral blood mononuclear cells (PBMCs) were obtained from patients with
      aBD (n = 30), patients with iBD (n = 31), and healthy control subjects (HCs; n =
      30). sCD40L plasma concentration was determined in individual samples. A pool of
      plasma for each group was created. In some experiments, plasma pools were treated
      with recombinant CD40 (rhCD40-muIg) for sCD40L blockade. NET release and H2O2/O2-
      production were determined after stimulation with phorbol 12-myristate 13
      acetate, sCD40L, or plasma pool. Flow cytometric analysis was performed to
      evaluate the expression of (1) CD40, Mac-1, and phosphorylated NF-kappaB p65 on
      neutrophils and monocytes and (2) CD40L on activated T cells and platelets. CD40L
      gene expression in PBMCs was determined by qRT-PCR. RESULTS: sCD40L plasma levels
      were significantly higher in patients with iBD (median 17,234, range 2346-19,279
      pg/ml) and patients with aBD (median 18,289, range 413-19,883 pg/ml) than in HCs
      (median 47.5, range 33.7-26.7 pg/ml; p < 0.001). NET release was constitutively
      increased in BD compared with HC. NET release and H2O2/O2- were higher after
      stimulation with sCD40L or BD plasma and decreased after sCD40L blockade. Mac-1
      expression was constitutively increased in neutrophils of patients with aBD (88.7
      +/- 13.2% of cells) and patients with iBD (89.2 +/- 20.1% of cells) compared with
      HC (27.1 +/- 18.8% of cells; p < 0.01). CD40 expression on phagocytes and CD40L
      expression on platelets were similar in the three groups. PBMCs as well as
      nonactivated and activated CD4+ T cells from patients with BD showed higher CD40L
      expression. CONCLUSIONS: Plasma from patients with aBD exerts a stimulus on NET
      release and oxidative burst, probably induced by sCD40L.

PMID- 29052525
TI  - Epigenetic mediated zinc finger protein 671 downregulation promotes cell
      proliferation and tumorigenicity in nasopharyngeal carcinoma by inhibiting cell
      cycle arrest.
AB  - BACKGROUND: Epigenetic abnormalities play important roles in nasopharyngeal
      cancer (NPC), however, the epigenetic changes associated with abnormal cell
      proliferation remain unclear. METHODS: We detected epigenetic change of ZNF671 in
      NPC tissues and cell lines by bisulfite pyrosequencing. We evaluated zinc finger
      protein 671 (ZNF671) expression in NPC cell lines and clinical tissues using real
      time PCR and western blotting. Then, we established NPC cell lines that stably
      overexpressed ZNF671 and knocked down ZNF671 expression to explore its function
      in NPC in vitro and in vivo. Additionally, we investigated the potential
      mechanism of ZNF671 by identifying the mitotic spindle and G2/M checkpoint
      pathways pathway downstream genes using gene set enrichment analysis, flow
      cytometry and western blotting. RESULTS: ZNF671 was hypermethylated in NPC
      tissues and cell lines. The mRNA and protein expression of ZNF671 was down
      regulated in NPC tissues and cell lines and the mRNA expression could be
      upregulated after the demethylation agent 5-aza-2'-deoxycytidine treatment.
      Overexpression of ZNF671 suppressed NPC cell proliferation and colony formation
      in vitro; silencing ZNF671 using a siRNA had the opposite effects. Additionally,
      overexpression of ZNF671 reduced the tumorigenicity of NPC cells in xenograft
      model in vivo. The mechanism study determined that overexpressing ZNF671 induced
      S phase arrest in NPC cells by upregulating p21 and downregulating cyclin D1 and
      c-myc. CONCLUSIONS: Epigenetic mediated zinc finger protein 671 downregulation
      promotes cell proliferation and enhances tumorigenicity by inhibiting cell cycle
      arrest in NPC, which may represent a novel potential therapeutic target.

PMID- 29052526
TI  - Cardiac magnetic resonance imaging-indeterminate/negative cardiac sarcoidosis
      revealed by 18F-fluorodeoxyglucose-positron emission tomography: two case reports
      and a review of the literature.
AB  - BACKGROUND: Sarcoidosis is an inflammatory disorder of immune dysregulation
      characterized by non-caseating granulomas that can affect any organ. Cardiac
      sarcoidosis is an under-recognized entity that has a heterogeneous presentation
      and may occur independently or with any severity of systemic disease. Diagnosing
      cardiac sarcoidosis remains problematic with endomyocardial biopsies associated
      with a high risk of complications. Several diagnostic algorithms are currently
      available that rely on histopathology or clinical and radiological measures. The
      dominant mode of diagnostic imaging to date for cardiac sarcoidosis has been
      cardiac magnetic resonance imaging with gadolinium enhancement. CASE
      PRESENTATIONS: We report the cases of two adult patients: case 1, a 50-year-old
      white man who presented with severe congestive cardiac failure; and case 2, a 37
      year-old white woman who presented with complete heart block. Both patients had a
      background of untreated pulmonary sarcoidosis. Cardiac magnetic resonance imaging
      did not show evidence of sarcoidosis in either patient and both proceeded to 18F
      fluorodeoxyglucose-positron emission tomography scans that were highly suggestive
      of cardiac sarcoidosis. Both patients were systemically immunosuppressed with
      orally administered prednisone and methotrexate and had subsequent improvement by
      clinical and nuclear medicine imaging measures. CONCLUSIONS: Current consensus
      guidelines recommend all patients with sarcoidosis undergo screening for occult
      cardiac disease, with thorough history and examination, electrocardiogram, and
      transthoracic echocardiogram. If any abnormalities are detected, advanced cardiac
      imaging should follow. While cardiac magnetic resonance imaging identifies the
      majority of cardiac sarcoidosis, early disease may not be detected. These cases
      demonstrate 18F-fluorodeoxyglucose-positron emission tomography is warranted
      following an indeterminate or normal cardiac magnetic resonance imaging if
      clinical suspicion remains high. Unidentified and untreated cardiac sarcoidosis
      risks significant morbidity and mortality, but early detection can facilitate
      disease-modifying immunosuppression and cardiac-specific interventions.

PMID- 29052527
TI  - Negative genic switch of HER-2 in the primary tumor instead of the synchronous
      metastatic nodal lesions after neoadjuvant chemotherapy in a patient with primary
      HER2-positive breast cancer.
AB  - BACKGROUND: A few retrospective studies have indicated that neoadjuvant
      chemotherapy (NAC) in breast cancer may change biomarker profiles of the primary
      tumor. Little is known about the status of HER-2 gene of the synchronous nodal
      metastases when that of the residual tumor undergoes negative conversion in a
      neoadjuvant setting. CASE PRESENTATION: We describe a female patient with left
      breast cancer (T2N2M0) who underwent negative conversion of HER-2 in the primary
      tumor instead of the synchronous nodal lesions after NAC. Core needle biopsy
      showed invasive ductal carcinoma with HER2 immunohistochemistry (IHC) (2+) and
      amplified HER-2 gene determined by fluorescence in situ hybridization (FISH).
      Then, the patient underwent 4 cycles of anthracycline- and taxane-based NAC and
      subsequent left modified radical mastectomy. Postoperative pathology showed
      invasive ductal carcinoma involving 4 of 12 surgically excised axillary lymph
      nodes with HER2 IHC (1+) and FISH negative (HER2 gene not amplified) in the
      residual tumor of the breast specimen. Due to the negative genic switch of HER2
      after NAC, the patient rejected to accept trastuzumab. Under the patient's
      consent, the synchronous nodal lesions were further investigated and showed HER2
      IHC(-) but FISH positive (HER-2 gene amplified). Therefore, the patient agreed to
      accept adjuvant trastuzumab treatment every 3 weeks for 1 year. CONCLUSIONS: We
      propose further assessment of HER2 gene in the synchronous nodal metastases,
      especially when negative genic switch of HER-2 occurs in the primary tumor after
      NAC in order to tailor the systemic regimens for breast cancer patients.

PMID- 29052528
TI  - Different genetic architectures underlie crop responses to the same pathogen: the
      {Helianthus annuus * Phoma macdonaldii} interaction case for black stem disease
      and premature ripening.
AB  - BACKGROUND: Phoma macdonaldii has been reported as the causal agent of black stem
      disease (BS) and premature ripening (PR) on sunflower. PR is considered as the
      most widespread and detrimental disease on sunflower in France. While genetic
      variability and QTL mapping for partial resistance of sunflower to stem, collar
      and roots attacks have been reported on plantlets in controlled conditions, this
      work aims to describe the genetic variability in a subset of a sunflower lines,
      and for the first time to map QTL involved in PR resistance evaluated in field
      conditions using controlled inoculation. RESULTS: An efficient and reliable
      method for inoculation used in field experiments induced stem base necrosis on up
      to 98% of all plants. A significant genetic variability for PR resistance in the
      field was detected among the 20 inbred lines of the core collection tested across
      the two years. For QTL mapping, the PR resistance evaluation was performed on two
      recombinant inbred lines (RIL) populations derived from the crosses XRQxPSC8 and
      FUxPAZ2 in two different years. QTL analyses were based on a newly developed
      consensus genetic map comprising 1007 non-redundant molecular markers. In each of
      the two RIL populations, different QTL involved in PR partial sunflower
      resistance were detected. The most significant QTL were detected 49 days post
      infection (DPI) on LG10 (LOD 7.7) and on LG7 (LOD 12.1) in the XRQxPSC8 and
      FUxPAZ2 RIL population, respectively. In addition, different QTL were detected on
      both populations for PR resistance measured between 14 and 35 DPI. In parallel,
      the incidence of natural attack of P. macdonaldii resulting in BS disease was
      recorded, showing that in these populations, the genetic of resistance to both
      diseases is not governed by the same factors. CONCLUSION: This work provides the
      first insights on the genetic architecture of sunflower PR resistance in the
      field. Moreover, the separate studies of symptoms on different organs and in time
      series allowed the identification of a succession of genetic components involved
      in the sunflower resistance to PR and BS diseases caused by Phoma macdonaldii
      along the development of the {plant * pathogen} interaction.

PMID- 29052529
TI  - Evaluating a multi-component, community-based program to improve adherence and
      retention in care among adolescents living with HIV in Zimbabwe: study protocol
      for a cluster randomized controlled trial.
AB  - BACKGROUND: World Health Organization (WHO) adolescent HIV-testing and treatment
      guidelines recommend community-based interventions to support antiretroviral
      therapy (ART) adherence and retention in care, while acknowledging that the
      evidence to support this recommendation is weak. This cluster randomized
      controlled trial aims to evaluate the effectiveness and cost-effectiveness of a
      psychosocial, community-based intervention on HIV-related and psychosocial
      outcomes. METHODS/DESIGN: We are conducting the trial in two districts. Sixteen
      clinics were randomized to either enhanced ART-adherence support or standard of
      care. Eligible individuals (HIV-positive adolescents aged 13-19 years and
      eligible for ART) in both arms receive ART and adherence support provided by
      adult counselors and nursing staff. Adolescents in the intervention arm
      additionally attend a monthly support group, are allocated to a designated
      community adolescent treatment supporter, and followed up through a short message
      service (SMS) and calls plus home visits. The type and frequency of contact is
      determined by whether the adolescent is "stable" or in need of enhanced support.
      Stable adolescents receive a monthly home visit plus a weekly, individualized
      SMS. An additional home visit is conducted if participants miss a scheduled
      clinic appointment or support-group meeting. Participants in need of further,
      enhanced, support receive bi-weekly home visits, weekly phone calls and daily
      SMS. Caregivers of adolescents in the intervention arm attend a caregiver support
      group. Trial outcomes are assessed through a clinical, behavioral and
      psychological assessment conducted at baseline and after 48 and 96 weeks. The
      primary outcome is the proportion who have died or have virological failure
      (viral load >=1000 copies/ml) at 96 weeks. Secondary outcomes include virological
      failure at 48 weeks, retention in care (proportion of missed visits) and
      psychosocial outcomes at both time points. Statistical analyses will be conducted
      and reported in line with CONSORT guidelines for cluster randomized trials,
      including a flowchart. DISCUSSION: This study provides a unique opportunity to
      generate evidence of the impact of the on-going Zvandiri program, for adolescents
      living with HIV, on virological failure and psychosocial outcomes as delivered in
      a real-world setting. If found to reduce rates of treatment failure, this would
      strengthen support for further scale-up across Zimbabwe and likely the region
      more widely. TRIAL REGISTRATION: Pan African Clinical Trial Registry database,
      registration number PACTR201609001767322 (the Zvandiri trial). Retrospectively
      registered on 5 September 2016.

PMID- 29052530
TI  - Health impacts of chemical irritants used for crowd control: a systematic review
      of the injuries and deaths caused by tear gas and pepper spray.
AB  - BACKGROUND: Chemical irritants used in crowd control, such as tear gases and
      pepper sprays, are generally considered to be safe and to cause only transient
      pain and lacrimation. However, there are numerous reports that use and misuse of
      these chemicals may cause serious injuries. We aimed to review documented
      injuries from chemical irritants to better understand the morbidity and mortality
      associated with these weapons. METHODS: We conducted a systematic review using
      PRISMA guidelines to identify injuries, permanent disabilities, and deaths from
      chemical irritants worldwide between January 1, 1990 and March 15, 2015. We
      reviewed injuries to different body systems, injury severity, and potential risk
      factors for injury severity. We also assessed region, context and quality of each
      included article. RESULTS: We identified 31 studies from 11 countries. These
      reported on 5131 people who suffered injuries, two of whom died and 58 of whom
      suffered permanent disabilities. Out of 9261 total injuries, 8.7% were severe and
      required professional medical management, while 17% were moderate and 74.3% were
      minor. Severe injuries occurred to all body systems, with the majority of
      injuries impacting the skin and eyes. Projectile munition trauma caused 231
      projectile injuries, with 63 (27%) severe injuries, including major head injury
      and vision loss. Potentiating factors for more severe injury included
      environmental conditions, prolonged exposure time, and higher quantities of
      chemical agent in enclosed spaces. CONCLUSIONS: Although chemical weapons may
      have a limited role in crowd control, our findings demonstrate that they have
      significant potential for misuse, leading to unnecessary morbidity and mortality.
      A nuanced understanding of the health impacts of chemical weapons and mitigating
      factors is imperative to avoiding indiscriminate use of chemical weapons and
      associated health consequences.

PMID- 29052531
TI  - PTEN expression is upregulated by a RNA-binding protein RBM38 via enhancing its
      mRNA stability in breast cancer.
AB  - BACKGROUND: PTEN (phosphatase and tensin homolog gene on chromosome 10), a well
      characterized tumor suppressor, is a key regulator of the phosphatidylinositol-3
      kinase (PI3K)/AKT pathway involved in cell survival, metastasis and cell renewal.
      PTEN expression is closely related to the phenotype, prognosis and drug selection
      in breast cancer. It is mainly regulated by transcriptional and post
      transcriptional modifications. RNA binding motif protein 38 (RBM38), an RNA
      binding protein (RBP) and a target of P53 family, plays a crucial role in the
      regulation of cellular processing, especially in post-transcription regulation
      and gene transcription. In this study, we investigated a new post-transcription
      regulation mechanism of PTEN expression by RBM38 in breast cancer. METHODS:
      Immunohistochemistry, lentivirus transfections, Western blotting analysis, qRT
      PCR and ELISA were used to conduct the relation between RBM38 and PTEN. RNA
      immunoprecipitation, RNA electrophoretic mobility shift and dual-luciferase
      reporter assays were employed to identify the direct binding sites of RBM38 with
      PTEN transcript. Colony formation assay was conducted to confirm the function of
      PTEN in RBM38-induced growth suppression. RESULTS: PTEN expression was positively
      associated with the expression of RBM38 in breast cancer tissues and breast
      cancer cells. Moreover, RBM38 stabilized PTEN transcript to enhance PTEN
      expression via binding to multiple AU/U- rich elements (AREs) in 3'-untranslated
      region (3'-UTR) of PTEN transcript. Additionally, specific inhibitors of PTEN
      activity and small interfering (siRNA) of PTEN expression inhibited RBM38
      mediated suppression of proliferation, which implied that RBM38 acted as a tumor
      suppressor partly by enhancing PTEN expression. CONCLUSION: The present study
      revealed a new PTEN regulating mechanism that PTEN was positively regulated by
      RBM38 via stabilizing its transcript stability, which in turn alleviated RBM38
      mediated growth suppression.

PMID- 29052532
TI  - Stereotactic body radiation therapy (SBRT) for definitive treatment and as a
      bridge to liver transplantation in early stage inoperable Hepatocellular
      carcinoma.
AB  - BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging
      modality for definitive treatment of Hepatocellular carcinoma (HCC). MATERIALS
      AND METHODS: This retrospective study included all early stage HCC patients who
      were not candidates for primary resection and/or local therapy, treated with SBRT
      between 11/2011 and 1/2016. RESULTS: Twenty-three patients were included. The
      median age was 62 years; 70% males; 30% females; 70% viral hepatitis carriers;
      100% cirrhotic; 13 Child Pugh [CP]-A and 10 [CP]-B. The median tumor volume was
      12.7cm3 (range, 2.2-53.6 cm3). Treatment was well tolerated. With the exception
      of one patient who developed RILD, no other patient had significant changes in 12
      weeks of laboratory follow-up. SBRT was a bridge to transplantation in 16
      patients and 11 were transplanted.. No surgical difficulties or complications
      were reported following SBRT, and none of the transplanted patients had local
      progression before transplantation. The median prescribed dose to the tumor was
      54Gy (range, 30-54Gy), the median dose to the uninvolved liver was 6.0Gy(range,
      1.6-12.6Gy). With a median follow-up time of 12 months, the median overall
      survival for the 11 transplanted patients was not reached (range, 2.0-53.7+
      months) and was 23 months for the 12 non-transplanted patients. The median
      progression-free survival for the transplanted patients was not reached (54+
      months) and was 14.0 months for the non-transplanted patients. There was no SBRT
      related mortality. Liver explant post SBRT revealed pathological complete
      response in 3(27.3%), pathological partial response in 6(54.5%), and pathological
      stable disease in 2(18.2%) tumors. CONCLUSIONS: SBRT is safe and effective and
      can be used as a bridge to transplantation without comprising the surgical
      procedure.

PMID- 29052533
TI  - Establishing partnership with traditional birth attendants for improved maternal
      and newborn health: a review of factors influencing implementation.
AB  - BACKGROUND: Recent World Health Organization recommendations recognize the
      important role Traditional Birth Attendants (TBAs) can play in supporting the
      health of women and newborns. This paper provides an analysis of key factors that
      affect the implementation of interventions to develop partnerships with TBAs to
      promote improved access to skilled care at birth. METHODS: We conducted a
      secondary analysis of 20 papers identified through two systematic reviews that
      examined the effectiveness of interventions to find new roles for TBAs on
      maternal and newborn health outcomes, as well as papers identified through a
      systematic mapping of the maternal health literature. The Supporting the Use of
      Research Evidence framework (SURE) guided the thematic analysis to explore the
      perceptions of various stakeholders and implementation barriers and facilitators,
      as well as other contextual issues. RESULTS: This analysis identified countries
      that have implemented interventions to support the transition from birth with a
      TBA to birth with a skilled birth attendant. Drawing on the experiences of these
      countries, the analysis highlights factors that are important to consider when
      designing and implementing such interventions. Barriers to implementation
      included resistance to change in more traditional communities, negative attitudes
      between TBAs and skilled attendants and TBAs concerns about the financial
      implications of assuming new roles. Facilitating factors included stakeholder
      involvement in devising and implementing interventions, knowledge sharing between
      TBAs and skilled birth attendants, and formalised roles and responsibilities and
      remuneration for TBAs. CONCLUSIONS: The implementation barriers identified in
      this analysis could, if not addressed, prevent or discourage TBAs from carrying
      out newly defined roles supporting women in pregnancy and childbirth and linking
      them to the formal health system. This paper also identifies the factors that
      seem critical to success, which new programmes could consider adopting from the
      outset. In most cases a multi-faceted approach is needed to prepare TBAs and
      others for new roles, including the training of TBAs to strengthen their
      knowledge and skills to enable them to be able to assume new roles, alongside the
      sensitization of healthcare providers, communities, women and their families.
      Further research is required to map the transition process and stakeholder
      experiences in more detailed ways and to provide longer-term monitoring of
      existing interventions.

PMID- 29052534
TI  - Specialist advice may improve patient selection for decompression therapy
      following diving accidents: a retrospective observational study.
AB  - BACKGROUND: Even in a landlocked country like Switzerland recreational diving is
      becoming more and more popular. Smaller lakes in the Alps are located at an
      altitude of 2500 m above sea level. The incidence of diving accidents among all
      helicopter emergency service missions and the consecutive medical knowledge about
      decompression injuries is low. Thus, a collaboration between the Swiss Air
      Ambulance (Rega) and the divers alert network (DAN) was initiated to improve
      patient treatment and identification of decompression injury and necessity of
      hyperbaric oxygen therapy (HBO). METHODS: Retrospective observational study that
      includes all patients treated by the Rega which have been classified to have had
      a diving accident from 2005 to 2014. Patient and diving epidemiology was assessed
      and the impact of DAN collaboration on patient selection and identification of
      patients needing transport to HBO facilities were analysed. RESULTS: In the 10
      year observational period 116 patients with diving accidents were treated by
      Rega. Mean patient age was 40 (SD 11) years and 95 (82%) were male. If the Rega
      emergency physician suspected a decompression injury (DCI), without DAN contact
      27/28 (96%) of these patients were transported directly to a HBO facility,
      whereas with DAN contact only 53/63 (84%) needed transport to a HBO facility. DAN
      was involved in 66/96 (69%) of the cases with suspected DCI on scene, with a
      significant increase over time (p = 0.001). Mean flight time to HBO facilities
      was significantly longer (28.9, SD 17.7 min.), compared to non-HBO facilities
      (7.1, SD 3.2 min., p < 0.001). Due to specialist advice, patients may have been
      selected who finally did not need a transport to a HBO facility, although DCI was
      primarily suspected by the emergency physician on the scene. These patients
      experienced a significantly reduced flight time to the (non-HBO) hospital of 25.6
      (SD 6.5) min. (p < 0.001). DISCUSSION: Collaboration of DAN and Rega may allow a
      safe patient selection and a consecutive reduction of flight time and costs. Due
      to international collaborations, evacuation to HBO-facilities for acute
      recompression therapy can be provided by HEMS within less than 30 min all over
      Switzerland. CONCLUSIONS: For diving accidents among HEMS missions, specialist
      advice by diving medicine specialists (DAN) appears mandatory to accurately
      identify and transport patients with decompression injury, as exposure of
      emergency physicians towards diving accidents and the diagnosis of DCI is low.

PMID- 29052535
TI  - Large cell neuroendocrine carcinoma of the kidney with cardiac metastasis: a case
      report.
AB  - BACKGROUND: Primary large cell neuroendocrine carcinoma of the kidney is a rare
      and generally very aggressive disease. We present a case of a patient with
      primary large cell neuroendocrine carcinoma of the kidney with cardiac
      metastasis. CASE PRESENTATION: A 59-year-old Japanese man presented to his
      previous physician with hematuria. Computed tomography revealed masses in the
      heart and right kidney, and fluorodeoxyglucose-positron emission tomography
      showed abnormal uptake in the heart. A cardiac biopsy under transesophageal
      echocardiographic guidance revealed a metastatic tumor. Subsequently, multiple
      lung lesions were detected, and a right nephrectomy was performed after these
      metastases were suspected to have originated from renal carcinoma. Large cell
      neuroendocrine carcinoma of the kidney was ultimately diagnosed. Pancreatic
      metastasis was detected on computed tomography postoperatively. Three courses of
      chemotherapy with carboplatin and irinotecan were administered, and were
      temporarily effective against the metastatic lesions in the lungs and pancreas.
      However, our patient's general condition deteriorated with the progression of the
      lesions, and he died 9 months after his initial examination. CONCLUSIONS: Multi
      agent chemotherapy, including platinum-based drugs was effective against large
      cell neuroendocrine carcinoma metastases, albeit only temporarily. This is the
      first reported case of large cell neuroendocrine carcinoma with cardiac
      metastasis.

PMID- 29052536
TI  - Breathing new life into an old target: pulmonary disease drugs for Parkinson's
      disease therapy.
AB  - Increases in alpha-synuclein protein expression are suspected to increase the
      risk of the development of Parkinson's disease (PD). A recent study has
      demonstrated that beta2-adrenergic receptor (beta2AR) agonists decrease histone
      acetylation in the alpha-synuclein gene and suppress transcription. Coupled with
      the anti-inflammatory effects that are associated with beta2AR activation, this
      two-pronged attack holds promise for PD treatment and the development of new
      therapeutic approaches for this disease.

PMID- 29052537
TI  - Enhanced IFN-alpha production is associated with increased TLR7 retention in the
      lysosomes of palasmacytoid dendritic cells in systemic lupus erythematosus.
AB  - BACKGROUND: Interferon-alpha (IFN-alpha) is increased and plays an important role
      in the pathogenesis of systemic lupus erythematosus (SLE). Plasmacytoid dendritic
      cells (pDCs) are the main producer of IFN-alpha, but their IFN-alpha producing
      capacity has been shown to be unchanged or reduced when stimulated with a Toll
      like receptor 9 (TLR9) agonist in patients with SLE compared to in healthy
      individuals. In this study, we investigated the IFN-alpha-producing capacity of
      lupus pDCs under different stimulation. METHODS: pDCs from patients with SLE and
      healthy controls (HC) were stimulated with TLR9 or TLR7 agonist, and their IFN
      alpha producing capacity was examined by intracellular cytokine staining and flow
      cytometry. The correlation of IFN-alpha-producing capacity with serum IFN-alpha
      levels and disease activity was assessed. The effect of in vitro IFN-alpha
      exposure on IFN-alpha production by pDCs was examined. Localization of TLR7 in
      cellular compartments in pDCs was investigated. RESULTS: The IFN-alpha producing
      capacity of pDCs was reduced after TLR9 stimulation, but increased when
      stimulated with a TLR7 agonist in SLE compared to in HC. IFN-alpha production by
      pDCs upon TLR9 stimulation was reduced and the percentage of IFN-alpha+pDC was
      inversely correlated with disease activity and serum IFN-alpha levels. However,
      the TLR7 agonist-induced IFN-alpha producing capacity of lupus pDCs was enhanced
      and correlated with disease activity and serum IFN-alpha. Exposure to IFN-alpha
      enhanced IFN-alpha production of TLR7-stimulated pDCs, but reduced that of pDCs
      activated with a TLR9 agonist. TLR7 localization was increased in late
      endosome/lysosome compartments in pDCs from SLE patients. CONCLUSIONS: These
      findings indicate that enhanced TLR7 responses of lupus pDCs, owing to TLR7
      retention in late endosome/lysosome and exposure to IFN-alpha, are associated
      with the pathogenesis of SLE.

PMID- 29052538
TI  - Antimicrobial Resistance in Rhodococcus equi.
AB  - Pneumonia caused by Rhodococcus equi remains an important cause of disease and
      death in foals. The combination of a macrolide (erythromycin, azithromycin, or
      clarithromycin) with rifampin has been the recommended treatment for foals with
      clinical signs of infection caused by R. equi since the early 1980s with, until
      recently, only rare reports of resistance. Resistance to macrolides and rifampin
      in isolates of R. equi cultured from horses is increasing, with isolates
      resistant to all macrolides and rifampin now being cultured from up to 40% of
      infected foals at some farms. This text reviews the available data regarding
      antimicrobial resistance in R. equi, with emphasis on the molecular mechanisms of
      the recent emergence of resistance to macrolides and rifampin in equine isolates
      of R. equi.

PMID- 29052539
TI  - Engineering Diagnostic and Therapeutic Gut Bacteria.
AB  - Genetically engineered bacteria have the potential to diagnose and treat a wide
      range of diseases linked to the gastrointestinal tract, or gut. Such engineered
      microbes will be less expensive and invasive than current diagnostics and more
      effective and safe than current therapeutics. Recent advances in synthetic
      biology have dramatically improved the reliability with which bacteria can be
      engineered with the sensors, genetic circuits, and output (actuator) genes
      necessary for diagnostic and therapeutic functions. However, to deploy such
      bacteria in vivo, researchers must identify appropriate gut-adapted strains and
      consider performance metrics such as sensor detection thresholds, circuit
      computation speed, growth rate effects, and the evolutionary stability of
      engineered genetic systems. Other recent reviews have focused on engineering
      bacteria to target cancer or genetically modifying the endogenous gut microbiota
      in situ. Here, we develop a standard approach for engineering "smart probiotics,"
      which both diagnose and treat disease, as well as "diagnostic gut bacteria" and
      "drug factory probiotics," which perform only the former and latter function,
      respectively. We focus on the use of cutting-edge synthetic biology tools, gut
      specific design considerations, and current and future engineering challenges.

PMID- 29052540
TI  - Emergence of Bordetella holmesii as a Causative Agent of Whooping Cough,
      Barcelona, Spain.
AB  - We describe the detection of Bordetella holmesii as a cause of whooping cough in
      Spain. Prevalence was 3.9% in 2015, doubling to 8.8% in 2016. This emergence
      raises concern regarding the contribution of B. holmesii to the reemergence of
      whooping cough and the effectiveness of the pertussis vaccine.

PMID- 29052542
TI  - Wide-area measurement system-based supervision of protection schemes with minimum
      number of phasor measurement units.
AB  - Cascade tripping of power lines triggered by maloperation of zone-3 relays during
      stressed system conditions, such as load encroachment, power swing and voltage
      instability, has led to many catastrophic power failures worldwide, including
      Indian blackouts in 2012. With the introduction of wide-area measurement systems
      (WAMS) into the grids, real-time monitoring of transmission network condition is
      possible. A phasor measurement unit (PMU) sends time-synchronized data to a
      phasor data concentrator, which can provide a control signal to substation
      devices. The latency associated with the communication system makes WAMS suitable
      for a slower form of protection. In this work, a method to identify the faulted
      line using synchronized data from strategic PMU locations is proposed.
      Subsequently, a supervisory signal is generated for specific relays in the system
      for any disturbance or stressed condition. For a given system, an approach to
      decide the strategic locations for PMU placement is developed, which can be used
      for determining the minimum number of PMUs required for application of the
      method. The accuracy of the scheme is tested for faults during normal and
      stressed conditions in a New England 39-bus system simulated using EMTDC/PSCAD
      software. With such a strategy, maloperation of relays can be averted in many
      situations and thereby blackouts/large-scale disturbances can be prevented.This
      article is part of the themed issue 'Energy management: flexibility, risk and
      optimization'.

PMID- 29052543
TI  - Probabilistic stability analysis: the way forward for stability analysis of
      sustainable power systems.
AB  - Future power systems will be significantly different compared with their present
      states. They will be characterized by an unprecedented mix of a wide range of
      electricity generation and transmission technologies, as well as responsive and
      highly flexible demand and storage devices with significant temporal and spatial
      uncertainty. The importance of probabilistic approaches towards power system
      stability analysis, as a subsection of power system studies routinely carried out
      by power system operators, has been highlighted in previous research. However, it
      may not be feasible (or even possible) to accurately model all of the
      uncertainties that exist within a power system. This paper describes for the
      first time an integral approach to probabilistic stability analysis of power
      systems, including small and large angular stability and frequency stability. It
      provides guidance for handling uncertainties in power system stability studies
      and some illustrative examples of the most recent results of probabilistic
      stability analysis of uncertain power systems.This article is part of the themed
      issue 'Energy management: flexibility, risk and optimization'.

PMID- 29052541
TI  - Proteomic analysis of cell cycle progression in asynchronous cultures, including
      mitotic subphases, using PRIMMUS.
AB  - The temporal regulation of protein abundance and post-translational modifications
      is a key feature of cell division. Recently, we analysed gene expression and
      protein abundance changes during interphase under minimally perturbed conditions
      (Ly et al., 2014, 2015). Here, we show that by using specific intracellular
      immunolabelling protocols, FACS separation of interphase and mitotic cells,
      including mitotic subphases, can be combined with proteomic analysis by mass
      spectrometry. Using this PRIMMUS (PRoteomic analysis of Intracellular
      iMMUnolabelled cell Subsets) approach, we now compare protein abundance and
      phosphorylation changes in interphase and mitotic fractions from asynchronously
      growing human cells. We identify a set of 115 phosphorylation sites increased
      during G2, termed 'early risers'. This set includes phosphorylation of S738 on
      TPX2, which we show is important for TPX2 function and mitotic progression.
      Further, we use PRIMMUS to provide the first a proteome-wide analysis of protein
      abundance remodeling between prophase, prometaphase and anaphase.

PMID- 29052544
TI  - Detecting changes in real-time data: a user's guide to optimal detection.
AB  - The real-time detection of changes in a noisily observed signal is an important
      problem in applied science and engineering. The study of parametric optimal
      detection theory began in the 1930s, motivated by applications in production and
      defence. Today this theory, which aims to minimize a given measure of detection
      delay under accuracy constraints, finds applications in domains including radar,
      sonar, seismic activity, global positioning, psychological testing, quality
      control, communications and power systems engineering. This paper reviews
      developments in optimal detection theory and sequential analysis, including
      sequential hypothesis testing and change-point detection, in both Bayesian and
      classical (non-Bayesian) settings. For clarity of exposition, we work in discrete
      time and provide a brief discussion of the continuous time setting, including
      recent developments using stochastic calculus. Different measures of detection
      delay are presented, together with the corresponding optimal solutions. We
      emphasize the important role of the signal-to-noise ratio and discuss both the
      underlying assumptions and some typical applications for each formulation.This
      article is part of the themed issue 'Energy management: flexibility, risk and
      optimization'.

PMID- 29052545
TI  - Robust estimation of risks from small samples.
AB  - Data-driven risk analysis involves the inference of probability distributions
      from measured or simulated data. In the case of a highly reliable system, such as
      the electricity grid, the amount of relevant data is often exceedingly limited,
      but the impact of estimation errors may be very large. This paper presents a
      robust non-parametric Bayesian method to infer possible underlying distributions.
      The method obtains rigorous error bounds even for small samples taken from ill
      behaved distributions. The approach taken has a natural interpretation in terms
      of the intervals between ordered observations, where allocation of probability
      mass across intervals is well specified, but the location of that mass within
      each interval is unconstrained. This formulation gives rise to a straightforward
      computational resampling method: Bayesian interval sampling. In a comparison with
      common alternative approaches, it is shown to satisfy strict error bounds even
      for ill-behaved distributions.This article is part of the themed issue 'Energy
      management: flexibility, risk and optimization'.

PMID- 29052546
TI  - Real option valuation of a decremental regulation service provided by electricity
      storage.
AB  - This paper is a quantitative study of a reserve contract for real-time balancing
      of a power system. Under this contract, the owner of a storage device, such as a
      battery, helps smooth fluctuations in electricity demand and supply by using the
      device to increase electricity consumption. The battery owner must be able to
      provide immediate physical cover, and should therefore have sufficient storage
      available in the battery before entering the contract. Accordingly, the following
      problem can be formulated for the battery owner: determine the optimal time to
      enter the contract and, if necessary, the optimal time to discharge electricity
      before entering the contract. This problem is formulated as one of optimal
      stopping, and is solved explicitly in terms of the model parameters and
      instantaneous values of the power system imbalance. The optimal operational
      strategies thus obtained ensure that the battery owner has positive expected
      economic profit from the contract. Furthermore, they provide explicit conditions
      under which the optimal discharge time is consistent with the overall objective
      of power system balancing. This paper also carries out a preliminary
      investigation of the 'lifetime value' aggregated from an infinite sequence of
      these balancing reserve contracts. This lifetime value, which can be viewed as a
      single project valuation of the battery, is shown to be positive and bounded.
      Therefore, in the long run such reserve contracts can be beneficial to commercial
      operators of electricity storage, while reducing some of the financial and
      operational risks in power system balancing.This article is part of the themed
      issue 'Energy management: flexibility, risk and optimization'.

PMID- 29052547
TI  - Partial differential equation methods for stochastic dynamic optimization: an
      application to wind power generation with energy storage.
AB  - A mixed financial/physical partial differential equation (PDE) can optimize the
      joint earnings of a single wind power generator (WPG) and a generic energy
      storage device (ESD). Physically, the PDE includes constraints on the ESD's
      capacity, efficiency and maximum speeds of charge and discharge. There is a mean
      reverting daily stochastic cycle for WPG power output. Physically, energy can
      only be produced or delivered at finite rates. All suppliers must commit hourly
      to a finite rate of delivery C, which is a continuous control variable that is
      changed hourly. Financially, we assume heavy 'system balancing' penalties in
      continuous time, for deviations of output rate from the commitment C Also, the
      electricity spot price follows a mean-reverting stochastic cycle with a strong
      evening peak, when system balancing penalties also peak. Hence the economic goal
      of the WPG plus ESD, at each decision point, is to maximize expected net present
      value (NPV) of all earnings (arbitrage) minus the NPV of all expected system
      balancing penalties, along all financially/physically feasible future paths
      through state space. Given the capital costs for the various combinations of the
      physical parameters, the design and operating rules for a WPG plus ESD in a
      finite market may be jointly optimizable.This article is part of the themed issue
      'Energy management: flexibility, risk and optimization'.

PMID- 29052548
TI  - Games and teams with shared constraints.
AB  - Energy systems of the future are envisaged to encompass multiple interacting
      autonomous entities. The theory of games provides the foundations for the design
      and analysis of such systems. This paper reviews models and results that would be
      of use for such analysis. Classically, games have involved players whose
      strategies are coupled only through the dependence of utility functions on
      strategies of other players. However, in many practical settings in the energy
      domain, system-level limitations bind the choices players can make. In 1965,
      Rosen (Econometrica33, 520-534 (doi:10.2307/1911749)) pioneered the study of a
      class of games where there is a common constraint, called a shared constraint,
      that couples the strategies available to the players. We discuss how this
      seemingly benign extension has important ramifications, ranging from the very
      definition of an equilibrium concept, to other key issues such as existence,
      uniqueness and efficiency of equilibria. We show how the presence of a shared
      constraint naturally leads to notions of a price and forms the motivations for
      more recent models. Although most of the paper has the character of a survey,
      occasionally we also prove new results.This article is part of the themed issue
      'Energy management: flexibility, risk and optimization'.

PMID- 29052549
TI  - A methodology to assess the economic impact of power storage technologies.
AB  - We present a methodology for assessing the economic impact of power storage
      technologies. The methodology is founded on classical approaches to the optimal
      stopping of stochastic processes but involves an innovation that circumvents the
      need to, ex ante, identify the form of a driving process and works directly on
      observed data, avoiding model risks. Power storage is regarded as a complement to
      the intermittent output of renewable energy generators and is therefore important
      in contributing to the reduction of carbon-intensive power generation. Our aim is
      to present a methodology suitable for use by policy makers that is simple to
      maintain, adaptable to different technologies and easy to interpret. The
      methodology has benefits over current techniques and is able to value, by
      identifying a viable optimal operational strategy, a conceived storage facility
      based on compressed air technology operating in the UK.This article is part of
      the themed issue 'Energy management: flexibility, risk and optimization'.

PMID- 29052550
TI  - An input-to-state stability approach to verify almost global stability of a
      synchronous-machine-infinite-bus system.
AB  - Conditions for almost global stability of an operating point of a realistic model
      of a synchronous generator with constant field current connected to an infinite
      bus are derived. The analysis is conducted by employing the recently proposed
      concept of input-to-state stability (ISS)-Leonov functions, which is an extension
      of the powerful cell structure principle developed by Leonov and Noldus to the
      ISS framework. Compared with the original ideas of Leonov and Noldus, the ISS
      Leonov approach has the advantage of providing additional robustness guarantees.
      The efficiency of the derived sufficient conditions is illustrated via numerical
      experiments.This article is part of the themed issue 'Energy management:
      flexibility, risk and optimization'.

PMID- 29052551
TI  - Planning low-carbon electricity systems under uncertainty considering operational
      flexibility and smart grid technologies.
AB  - Electricity grid operators and planners need to deal with both the rapidly
      increasing integration of renewables and an unprecedented level of uncertainty
      that originates from unknown generation outputs, changing commercial and
      regulatory frameworks aimed to foster low-carbon technologies, the evolving
      availability of market information on feasibility and costs of various
      technologies, etc. In this context, there is a significant risk of locking-in to
      inefficient investment planning solutions determined by current deterministic
      engineering practices that neither capture uncertainty nor represent the actual
      operation of the planned infrastructure under high penetration of renewables. We
      therefore present an alternative optimization framework to plan electricity grids
      that deals with uncertain scenarios and represents increased operational details.
      The presented framework is able to model the effects of an array of flexible,
      smart grid technologies that can efficiently displace the need for conventional
      solutions. We then argue, and demonstrate via the proposed framework and an
      illustrative example, that proper modelling of uncertainty and operational
      constraints in planning is key to valuing operationally flexible solutions
      leading to optimal investment in a smart grid context. Finally, we review the
      most used practices in power system planning under uncertainty, highlight the
      challenges of incorporating operational aspects and advocate the need for new and
      computationally effective optimization tools to properly value the benefits of
      flexible, smart grid solutions in planning. Such tools are essential to
      accelerate the development of a low-carbon energy system and investment in the
      most appropriate portfolio of renewable energy sources and complementary enabling
      smart technologies.This article is part of the themed issue 'Energy management:
      flexibility, risk and optimization'.

PMID- 29052552
TI  - Coordinated single-phase control scheme for voltage unbalance reduction in low
      voltage network.
AB  - Low voltage (LV) distribution systems are typically unbalanced in nature due to
      unbalanced loading and unsymmetrical line configuration. This situation is
      further aggravated by single-phase power injections. A coordinated control scheme
      is proposed for single-phase sources, to reduce voltage unbalance. A consensus
      based coordination is achieved using a multi-agent system, where each agent
      estimates the averaged global voltage and current magnitudes of individual phases
      in the LV network. These estimated values are used to modify the reference power
      of individual single-phase sources, to ensure system-wide balanced voltages and
      proper power sharing among sources connected to the same phase. Further, the high
      X/R ratio of the filter, used in the inverter of the single-phase source, enables
      control of reactive power, to minimize voltage unbalance locally. The proposed
      scheme is validated by simulating a LV distribution network with multiple single
      phase sources subjected to various perturbations.This article is part of the
      themed issue 'Energy management: flexibility, risk and optimization'.

PMID- 29052553
TI  - Procuring load curtailment from local customers under uncertainty.
AB  - Demand side response (DSR) provides a flexible approach to managing constrained
      power network assets. This is valuable if future asset utilization is uncertain.
      However there may be uncertainty over the process of procurement of DSR from
      customers. In this context we combine probabilistic modelling, simulation and
      optimization to identify economically optimal procurement policies from
      heterogeneous customers local to the asset, under chance constraints on the
      adequacy of the procured DSR. Mathematically this gives rise to a search over
      permutations, and we provide an illustrative example implementation and case
      study.This article is part of the themed issue 'Energy management: flexibility,
      risk and optimization'.

PMID- 29052554
TI  - Energy management: flexibility, risk and optimization.

PMID- 29052555
TI  - Polarization rotation and the electrocaloric effect in barium titanate.
AB  - We study the electrocaloric effect in the classic ferroelectric BaTiO3 through a
      series of phase transitions driven by applied electric field and temperature. We
      find both negative and positive electrocaloric effects, with the negative
      electrocaloric effect, where temperature decreases with applied field, in
      monoclinic phases. Macroscopic polarization rotation is evident through the
      monoclinic and orthorhombic phases under applied field, and is responsible for
      the negative electrocaloric effect.

PMID- 29052556
TI  - Forewings match the formation of leading-edge vortices and dominate aerodynamic
      force production in revolving insect wings.
AB  - In many flying insects, forewings and hindwings are coupled mechanically to
      achieve flapping flight synchronously while being driven by action of the
      forewings. How the forewings and hindwings as well as their morphologies
      contribute to aerodynamic force production and flight control remains unclear.
      Here we address the point that the forewings can produce most of the aerodynamic
      forces even with the hindwings removed through a computational fluid dynamic
      study of three revolving insect wing models, which are identical to the wing
      morphologies and Reynolds numbers of hawkmoth (Manduca sexta), bumblebee (Bombus
      ignitus) and fruitfly (Drosophila melanogaster). We find that the forewing
      morphologies match the formation of leading-edge vortices (LEV) and are
      responsible for generating sufficient lift forces at the mean angles of attack
      and the Reynolds numbers where the three representative insects fly. The LEV
      formation and pressure loading keep almost unchanged with the hindwing removed,
      and even lead to some improvement in power factor and aerodynamic efficiency.
      Moreover, our results indicate that the size and strength of the LEVs can be well
      quantified with introduction of a conical LEV angle, which varies remarkably with
      angles of attack and Reynolds numbers but within the forewing region while
      showing less sensitivity to the wing morphologies. This implies that the forewing
      morphology very likely plays a dominant role in achieving low-Reynolds number
      aerodynamic performance in natural flyers as well as in revolving and/or flapping
      micro air vehicles.

PMID- 29052557
TI  - Determination of volatile organic compounds in exhaled breath of heart failure
      patients by needle trap micro-extraction coupled with gas chromatography-tandem
      mass spectrometry.
AB  - The analytical performances of needle trap micro-extraction (NTME) coupled with
      gas chromatography-tandem mass spectrometry were evaluated by analyzing a mixture
      of twenty-two representative breath volatile organic compounds (VOCs) belonging
      to different chemical classes (i.e. hydrocarbons, ketones, aldehydes, aromatics
      and sulfurs). NTME is an emerging technique that guarantees detection limits in
      the pptv range by pre-concentrating low volumes of sample, and it is particularly
      suitable for breath analysis. For most VOCs, detection limits between 20 and 500
      pptv were obtained by pre-concentrating 25 ml of a humidified standard gas
      mixture at a flow rate of 15 ml min-1. For all compounds, inter- and intra-day
      precisions were always below 15%, confirming the reliability of the method. The
      procedure was successfully applied to the analysis of exhaled breath samples
      collected from forty heart failure (HF) patients during their stay in the
      University Hospital of Pisa. The majority of patients (about 80%) showed a
      significant decrease of breath acetone levels (a factor of 3 or higher) at
      discharge compared to admission (acute phase) in correspondence to the improved
      clinical conditions during hospitalization, thus making this compound eligible as
      a biomarker of HF exacerbation.

PMID- 29052558
TI  - Cesarean Section Rate in Singleton Primiparae and Related Factors in Beijing,
      China.
AB  - BACKGROUND: The cesarean section rate (CSR) has been a main concern worldwide.
      The present study aimed to investigate the CSR in Beijing, China, and to analyze
      the related factors of CS delivery. METHODS: An observational study was conducted
      in 15 medical centers in Beijing using a systemic cluster sampling method. In
      total, 15,194 pregnancies were enrolled in the study between June 20, 2013 and
      November 30, 2013. Independent t-tests and Pearson's Chi-square test were used to
      examine differences between two groups, and related factors of the CSR were
      examined by multivariable logistic regression. RESULTS: The CSR was 41.9%
      (4471/10,671) in singleton primiparae. Women who were more than 35 years old had
      a 7.4-fold increased risk of CS delivery compared with women <25 years old (odd
      ratio [OR] = 7.388, 95% confidence interval [CI] = 5.561-9.816, P < 0.001).
      Prepregnancy obese women had a 2-fold increased risk of CS delivery compared with
      prepregnancy normal weight women (OR = 2.058, 95% CI = 1.640-2.584, P < 0.001).
      The excessive weight gain group had a 1.4-fold increased risk of CS delivery
      compared with the adequate weight gain group (OR = 1.422, 95% CI = 1.289-1.568, P
      < 0.001). Gestational diabetes mellitus (GDM) women and DM women had an increased
      risk of CS delivery (1.2- and 1.7-fold, respectively) compared with normal blood
      glucose women. Women who were born in rural areas had a lower risk of CS delivery
      than did those who were born in urban areas (OR = 0.696, 95% CI = 0.625-0.775, P
      < 0.001). The risk of CS delivery gradually increased with a decreasing education
      level. Neonates weighing 3000-3499 g had the lowest CSR (36.2%). Neonates
      weighing <2500 g had a 2-fold increased risk of CS delivery compared with
      neonates weighing 3000-3499 g (OR = 2.020, 95% CI = 1.537-2.656, P < 0.001).
      Neonates weighing >=4500 g had an 8.3-fold increased risk of CS delivery compared
      with neonates weighing 3000-3499 g (OR = 8.313, 95% CI = 4.436-15.579, P <
      0.001). CONCLUSIONS: Maternal age, prepregnancy body mass index, gestational
      weight gain, blood glucose levels, residence, education level, and singleton
      fetal birth weight are all factors that might significantly affect the CSR.

PMID- 29052560
TI  - Characteristics of Mandarin Open-set Word Recognition Development among Chinese
      Children with Cochlear Implants.
AB  - BACKGROUND: Cochlear implants (CIs) can improve speech recognition for children
      with severe congenital hearing loss, and open-set word recognition is an
      important efficacy measure. This study examined Mandarin open-set word
      recognition development among Chinese children with CIs and normal hearing (NH).
      METHODS: This study included 457 children with CIs and 131 children with NH, who
      completed the Mandarin lexical neighborhood test. The results for children at 1-8
      years after receiving their CIs were compared to those from the children with NH
      using linear regression analysis and analysis of variance. RESULTS: Recognition
      of disyllabic easy words, disyllabic hard words, monosyllabic easy words, and
      monosyllabic hard words increased with time after CI implantation. Scores for
      cases with implantation before 3 years old were significantly better than those
      for implantation after 3 years old. There were significant differences in open
      set word recognition between the CI and NH groups. For implantation before 2
      years, there was no significant difference in recognition at the ages of 6-7
      years, compared to 3-year-old children with NH, or at the age of 10 years,
      compared to 6-year-old children with NH. For implantation before 3 years, there
      was no significant difference in recognition at the ages of 8-9 years, compared
      to 3-year-old children with NH, or at the age of 10 years, compared to 6-year-old
      children with NH. For implantation after 3 years, there was a significant
      difference in recognition at the age of 13 years, compared to 3-year-old children
      with NH. CONCLUSIONS: Mandarin open-set word recognition increased with time
      after CI implantation, and the age at implantation had a significant effect on
      long-term speech recognition. Chinese children with CIs had delayed but similar
      development of recognition, compared to normal children. Early CI implantation
      can shorten the gap between children with CIs and normal children.

PMID- 29052559
TI  - Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal
      Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical
      Study.
AB  - BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal
      dysfunction usually exhibits an irreversible course, and available treatments for
      delaying the progression to end-stage renal disease are limited. This study aimed
      to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing
      particles, for delaying renal dysfunction in patients with stage 3b-4 CKD.
      METHODS: The present study was a prospective, randomized, double-blind, placebo
      controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD
      patients with an estimated glomerular filtration rate (eGFR) between 20 and 45
      ml.min-1.1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11
      Chinese provinces. Patients were randomized in a 1:1 ratio to either a test
      group, which was administered Niaoduqing particles 5 g thrice daily and 10 g
      before bedtime for 24 weeks, or a control group, which was administered a placebo
      using the same methods. The primary endpoints were changes in baseline serum
      creatinine (Scr) and eGFR after completion of treatment. The primary endpoints
      were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present
      study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A
      total of 292 participants underwent the ITT analysis. At 24 weeks, the median
      (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9)
      MUmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and
      the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml.min-1.1.73 m
      2, respectively (Z = -2.408, P = 0.016). There were no significant differences in
      adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and
      effectively delayed CKD progression in patients with stage 3b-4 CKD. This
      traditional Chinese medicine may be a promising alternative medication for
      patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese
      Clinical Trial Register, ChiCTR-TRC-12002448;
      http://www.chictr.org.cn/showproj.aspx?proj=7102.

PMID- 29052561
TI  - A Bayesian Stepwise Discriminant Model for Predicting Risk Factors of Preterm
      Premature Rupture of Membranes: A Case-control Study.
AB  - BACKGROUND: Preterm premature rupture of membrane (PPROM) can lead to serious
      consequences such as intrauterine infection, prolapse of the umbilical cord, and
      neonatal respiratory distress syndrome. Genital infection is a very important
      risk which closely related with PPROM. The preliminary study only made
      qualitative research on genital infection, but there was no deep and clear
      judgment about the effects of pathogenic bacteria. This study was to analyze the
      association of infections with PPROM in pregnant women in Shaanxi, China, and to
      establish Bayesian stepwise discriminant analysis to predict the incidence of
      PPROM. METHODS: In training group, the 112 pregnant women with PPROM were
      enrolled in the case subgroup, and 108 normal pregnant women in the control
      subgroup using an unmatched case-control method. The sociodemographic
      characteristics of these participants were collected by face-to-face interviews.
      Vaginal excretions from each participant were sampled at 28-36+6 weeks of
      pregnancy using a sterile swab. DNA corresponding to Chlamydia trachomatis (CT),
      Ureaplasma urealyticum (UU), Candida albicans, group B streptococci (GBS), herpes
      simplex virus-1 (HSV-1), and HSV-2 were detected in each participant by real-time
      polymerase chain reaction. A model of Bayesian discriminant analysis was
      established and then verified by a multicenter validation group that included 500
      participants in the case subgroup and 500 participants in the control subgroup
      from five different hospitals in the Shaanxi province, respectively. RESULTS: The
      sociological characteristics were not significantly different between the case
      and control subgroups in both training and validation groups (all P > 0.05). In
      training group, the infection rates of UU (11.6% vs. 3.7%), CT (17.0% vs. 5.6%),
      and GBS (22.3% vs. 6.5%) showed statistically different between the case and
      control subgroups (all P < 0.05), log-transformed quantification of UU, CT, GBS,
      and HSV-2 showed statistically different between the case and control subgroups
      (P < 0.05). All etiological agents were introduced into the Bayesian stepwise
      discriminant model showed that UU, CT, and GBS infections were the main
      contributors to PPROM, with coefficients of 0.441, 3.347, and 4.126,
      respectively. The accuracy rates of the Bayesian stepwise discriminant analysis
      between the case and control subgroup were 84.1% and 86.8% in the training and
      validation groups, respectively. CONCLUSIONS: This study established a Bayesian
      stepwise discriminant model to predict the incidence of PPROM. The UU, CT, and
      GBS infections were discriminant factors for PPROM according to a Bayesian
      stepwise discriminant analysis. This model could provide a new method for the
      early predicting of PPROM in pregnant women.

PMID- 29052562
TI  - Clinical Profile and Significance of Mucocutaneous Lesions of Primary Sjogren's
      Syndrome: A Large Cross-sectional Study with 874 Patients.
AB  - BACKGROUND: Mucocutaneous lesions are common features of primary Sjogren's
      syndrome (pSS), but only a few studies have focused on them. To demonstrate the
      profile of mucocutaneous lesions of pSS and further explore their potential
      clinical significance, we performed a cross-sectional study on 874 patients.
      METHODS: Demographic data, clinical manifestations, and laboratory results of 874
      pSS patients were collected. Patients were divided into two groups according to
      the presence of mucocutaneous lesions. Differences in primary symptoms and
      systemic impairments between the two groups were analyzed. Results of laboratory
      tests were also compared after excluding those who had taken corticosteroid from
      both groups. One-year follow-up was done, and occurrences of various new
      complications were compared. RESULTS: Among the 874 pSS patients, 181 patients
      had mucocutaneous lesions, accounting for 20.7%. Multiple mucocutaneous
      manifestations were displayed, and the top four most common types of lesions were
      purpuric eruptions (39.8%), urticaria (23.8%), Raynaud's phenomenon (14.9%), and
      angular stomatitis (9.9%). Incidences of pulmonary interstitial fibrosis,
      pulmonary bullae, leukopenia, and anemia were significantly higher among patients
      with mucocutaneous lesions (P < 0.05). Increase in IgG and decrease in C4 among
      patients with mucocutaneous lesions displayed statistical significance after
      excluding patients from both groups who had taken corticosteroid (P < 0.05).
      After one-year follow-up, patients with mucocutaneous lesions presented a
      slightly higher incidence of new complications compared to those without.
      CONCLUSIONS: Mucocutaneous manifestations of pSS patients were common and
      diverse. Patients with mucocutaneous manifestations had more systemic damages,
      higher level of IgG, and lower level of serum C4, suggesting a higher activity of
      the primary disease.

PMID- 29052563
TI  - Predictive Score Model for Delayed Graft Function Based on Easily Available
      Variables before Kidney Donation after Cardiac Death.
AB  - BACKGROUND: How to evaluate the quality of donation after cardiac death (DCD)
      kidneys has become a critical problem in kidney transplantation in China. Hence,
      the aim of this study was to develop a simple donor risk score model to evaluate
      the quality of DCD kidneys before DCD. METHODS: A total of 543 qualified kidneys
      were randomized in a 2:1 manner to create the development and validation cohorts.
      The donor variables in the development cohort were considered as candidate
      univariate predictors of delayed graft function (DGF). Multivariate logistic
      regression was then used to identify independent predictors of DGF with P < 0.05.
      Date from validation cohort were used to validate the donor scoring model.
      RESULTS: Based on the odds ratios, eight identified variables were assigned a
      weighted integer; the sum of the integer was the total risk score for each
      kidney. The donor risk score, ranging from 0 to 28, demonstrated good
      discriminative power with a C-statistic of 0.790. Similar results were obtained
      from validation cohort with C-statistic of 0.783. Based on the obtained
      frequencies of DGF in relation to different risk scores, we formed four risk
      categories of increasing severity (scores 0-4, 5-9, 10-14, and 15-28).
      CONCLUSIONS: The scoring model might be a good noninvasive tool for assessing the
      quality of DCD kidneys before donation and potentially useful for physicians to
      make optimal decisions about donor organ offers.

PMID- 29052564
TI  - Reference Intervals of Mitochondrial DNA Copy Number in Peripheral Blood for
      Chinese Minors and Adults.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) content measured by different techniques
      cannot be compared between studies, and age- and tissue-related control values
      are hardly available. In the present study, we aimed to establish the normal
      reference range of mtDNA copy number in the Chinese population. METHODS: Two
      healthy cohorts of 200 Chinese minors (0.1-18.0 years) and 200 adults (18.0-88.0
      years) were recruited. Then, they were further categorized into eight age groups.
      The absolute mtDNA copy number per cell was measured by a quantitative real-time
      polymerase chain reaction. We subsequently used this range to evaluate mtDNA
      content in four patients (0.5-4.0 years) with molecularly proven mitochondrial
      depletion syndromes (MDSs) and 83 cases of mitochondrial disease patients
      harboring the m.3243A>G mutation. RESULTS: The reference range of mtDNA copy
      number in peripheral blood was 175-602 copies/cell (mean: 325 copies/cell) in
      minors and 164-500 copies/cell (mean: 287 copies/cell) in adults. There was a
      decreasing trend in mtDNA copy number in blood with increasing age, especially in
      0-2-year-old and >50-year-old donors. The mean mtDNA copy number level among the
      mitochondrial disease patients with m.3243A>G mutation was significantly higher
      than that of healthy controls. The mtDNA content of POLG, DGUOK, TK2, and SUCLA2
      genes in blood samples from MDS patients was reduced to 25%, 38%, 32%, and 24%,
      respectively. CONCLUSIONS: We primarily establish the reference intervals of
      mtDNA copy number, which might contribute to the clinical diagnosis and
      monitoring of mitochondrial disease.

PMID- 29052565
TI  - Factors Predicting Late Rectal Disorders after Radiation Therapy for Prostate
      Cancer.
AB  - BACKGROUND: Although various studies have been conducted on the effects of
      radiation therapy for prostate cancer, rectal toxicity after radiation therapy
      for prostate cancer, which is an important late adverse event associated with
      radiation therapy, has not been sufficiently examined. This study aimed to assess
      the associations of late rectal disorder (LRD) with dosimetric, anatomic, and
      clinical factors in patients with prostate cancer who underwent three-dimensional
      conformal radiation therapy (3D-CRT). METHODS: We retrospectively analyzed 104
      patients undergoing 3D-CRT between January 2009 and October 2011. Thirty patients
      were administered anticoagulation/antiplatelet (AC/AP) agents. The standard dose
      was 74 Gy. Uni- and multi-variate analyses were performed to identify factors
      predictive of LRD after 3D-CRT. RESULTS: The median follow-up period was 66
      (range: 14-87) months. LRD occurred in 10.6% (11/104) of patients. The median
      time from RT to LRD was 15 months (range: 7-41 months). Sixty-four percent of
      those with LRD (7/11 patients) had been given AC/AP agents. Fifty-five (6/11)
      patients had severe internal iliac artery calcification. By univariate analysis,
      significant predictors of LRD were internal iliac artery calcification,
      administration of AC/AP agents, and age. Being very elderly was the significant
      predictor identified by multivariate analysis (P = 0.0276). For patients
      receiving AC/AP agents and those with severe internal iliac artery calcification,
      the LRD incidences were 23.3% (7/30 patients) and 23.1% (6/26 patients),
      respectively, and being 75 years of age or older was a significant predictor in
      these subsets. CONCLUSIONS: Our results suggest advanced age, administration of
      AC/AP agents, and severe internal iliac artery calcification to be risk factors
      for LRD in patients undergoing standard RT. Therefore, it is necessary to
      administer radiation with particular caution in the very elderly, especially
      those receiving AC/AP agents and/or with severe internal iliac artery
      calcification.

PMID- 29052566
TI  - Analysis on Inpatient Health Expenditures of Renal Cell Carcinoma in a Grade-A
      Tertiary Hospital in Beijing.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is the most common type of malignant renal
      tumors with a growing incidence in the recent years. This study aimed to
      investigate the influencing factors and variation trend of hospitalization
      expenditures among RCC patients in a single-centered hospital in Beijing during 5
      consecutive years and to find the major cost items and fluctuation tendency of
      inpatient medical expenditures. METHODS: The information of medical expenditures
      among RCC patients in a Grade-A tertiary hospital during the years 2012-2016 was
      investigated to find the main cost items and changes affecting the medical cost
      structure. Gray correlation method was adopted in quantitative analysis to
      analyze the composition of medical expenditures, and the variation of
      hospitalization expense structure during the five years was studied by analyzing
      the degree of structural variation. RESULTS: The cost item constitution of the
      hospitalization expenditures among RCC patients was relatively stable in the
      sample hospital during the past five years. To be specific, drug costs accounted
      for the largest proportion of medical expenditures each year, with the highest of
      37.81% in 2012, and showed a slowly declining tendency in the coming years. The
      cost item with the highest correlation degree was drug costs, with the value of
      1.0000; followed by the costs of surgeries, 0.8423. Furthermore, drug costs
      shared the largest proportion (40.95%) of structural variation, followed by the
      costs of surgeries (18.35%). CONCLUSIONS: Drug costs are the major influencing
      factors of the hospitalization expenditures among RCC patients. Thus, reasonable
      control on excessive drugs as well as the standardization of the diagnosis and
      treatment behaviors is conducive in reducing medical expenditures as well as
      easing patients' economic burdens. Besides, the positive growth on surgery costs
      suggests that the labor value of medical staffs has been gradually recognized.

PMID- 29052567
TI  - Interventional Bronchoscopic Therapy in Adult Patients with Tracheobronchial
      Mucoepidermoid Carcinoma.
AB  - BACKGROUND: Tracheobronchial mucoepidermoid carcinoma (MEC) is a rare airway
      tumor in adults for which surgery is considered a first-line treatment. However,
      some patients already lost the best opportunity of a surgical intervention when
      diagnoses are confirmed, and surgery causes considerable trauma resulting in
      partial loss of pulmonary function. Moreover, the tumor is resistant to
      radiotherapy and chemotherapy. These factors make the treatment of
      tracheobronchial MEC challenging. This study aimed to evaluate the safety and
      efficacy of interventional bronchoscopic therapy in adult patients with
      tracheobronchial MEC. METHODS: We retrospectively analyzed the clinical
      manifestations, bronchoscopic interventions, complications, and outcomes of 11
      adult patients with tracheobronchial MEC. Paired t-test was used to analyze the
      parameters of the American Thoracic Society Dyspnea Index and the Karnofsky Score
      before and after the first interventional bronchoscopic therapy. RESULTS: All
      tumors occurred in the main bronchus and were easily visualized by bronchoscopy.
      After interventional bronchoscopic therapy, the symptoms of all patients showed
      significant improvement. The American Thoracic Society Dyspnea Index decreased
      from 1.91 +/- 1.22 to 0.27 +/- 0.47 (t = 6.708, P < 0.001) and the Karnofsky
      Score increased from 78.18 +/- 16.62 to 95.46 +/- 8.20 (t = -5.190, P < 0.001).
      Bronchoscopic intervention did not result in serious complications or mortality.
      During the follow-up period between 3 and 96 months after the first therapy, the
      following results were noted: (1) among the eight patients with low-grade
      tracheobronchial MEC, only one patient had a relapse and agreed to surgical
      treatment; (2) among the three patients with high-grade tracheobronchial MEC, one
      patient required repeated bronchoscopic interventions, one patient died of
      pulmonary infection, and one patient died of systemic failure owing to tumor
      metastasis. CONCLUSIONS: Interventional bronchoscopic therapy, as an alternative
      treatment, shows promise in some adult patients with low-grade tracheobronchial
      MEC confined to the bronchus. However, for adult patients with high-grade
      tracheobronchial MEC, early diagnosis and surgical treatment are still strongly
      recommended.

PMID- 29052568
TI  - Genetic Testing of the mucin 1 gene-Variable Number Tandem Repeat Single Cytosine
      Insertion Mutation in a Chinese Family with Medullary Cystic Kidney Disease.
AB  - BACKGROUND: Medullary cystic kidney disease (MCKD) is clinically
      indistinguishable from several other autosomal-dominant renal diseases; thus,
      molecular genetic testing is needed to establish a definitive diagnosis. A
      specific type of single cytosine insertion in the variable number tandem repeat
      (VNTR) of the mucin 1 (MUC1) gene is the only known cause of MCKD1; however,
      genetic analysis of this mutation is difficult and not yet offered routinely. To
      identify the causative mutation/s and establish a definitive diagnosis in a
      Chinese family with chronic kidney disease, clinical assessments and genetic
      analysis were performed, including using a modified genotyping method to identify
      the MUC1- VNTR single cytosine insertion. METHODS: Clinical data from three
      patients in a Chinese family with chronic kidney disease were collected and
      evaluated. Linkage analysis was used to map the causative locus. Mutation
      analysis of uromodulin (UMOD) gene was performed using polymerase chain reaction
      (PCR) and direct sequencing. For MUC1 genotyping, the mutant repeat units were
      enriched by MwoI restriction, and then were amplified and introduced into pMD-18T
      vectors. The 192 clones per transformant were picked up and tested by colony PCR
      and second round of MwoI digestion. Finally, Sanger sequencing was used to
      confirm the MUC1 mutation. RESULTS: Clinical findings and laboratory results were
      consistent with a tubulointerstitial lesion. Linkage analysis indicated that the
      family was compatible with the MCKD1 locus. No mutations were found in UMOD gene.
      Using the modified MUC1 genotyping method, we detected the MUC1-VNTR single
      cytosine insertion events in three patients of the family; and mutation
      containing clones were 12/192, 14/192, and 5/96, respectively, in the three
      patients. CONCLUSIONS: Clinical and genetic findings could support the MCKD1
      diagnosis. The modified strategy has been demonstrated to be a practical way to
      detect MUC1 mutation.

PMID- 29052569
TI  - Analysis of the Expression of Angioarchitecture-related Factors in Patients with
      Cerebral Arteriovenous Malformation.
AB  - BACKGROUND: Cerebral arteriovenous malformation (cAVM) is a type of vascular
      malformation associated with vascular remodeling, hemodynamic imbalance, and
      inflammation. We detected four angioarchitecture-related cytokines to make a
      better understanding of the potential aberrant signaling in the pathogenesis of
      cAVM and found useful proteins in predicting the risk of cerebral hemorrhage.
      METHODS: Immunohistochemical analysis was conducted on specimens from twenty
      patients with cAVM diagnosed via magnetic resonance imaging and digital
      subtraction angiography and twenty primary epilepsy controls using antibodies
      against vascular endothelial growth factor receptor-2 (VEGFR-2), matrix
      metalloproteinase-9 (MMP-9), vascular cell adhesion molecule (VCAM-1), and
      endothelial nitric oxide synthase (eNOS). Western blotting and real-time
      fluorescent quantitative polymerase chain reaction (PCR) were performed to
      determine protein and mRNA expression levels. Student's t-test was used for
      statistical analysis. RESULTS: VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels
      increased in patients with cAVM compared with those in normal cerebral vascular
      tissue, as determined by immunohistochemical analysis. In addition, Western
      blotting and real-time PCR showed that the protein and mRNA expression levels of
      VEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the
      control group, all the differences mentioned were statistically significant (P <
      0.05). CONCLUSIONS: VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients
      with cAVM and might play important roles in angiogenesis, vascular remodeling,
      and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be
      potential excellent group proteins in predicting the risk of cerebral hemorrhage
      at arteriovenous malformation.

PMID- 29052573
TI  - Surgical Intervention for Behcet's Disease with Aorta Aneurysm and
      Pseudoaneurysm: Opposite Outcomes in Two Cases.

PMID- 29052572
TI  - Delirium in Intensive Care Unit Patients: Ten Important Points of Understanding.

PMID- 29052570
TI  - Chinese Multidisciplinary Expert Consensus on the Diagnosis and Treatment of
      Hyperuricemia and Related Diseases.

PMID- 29052571
TI  - Susceptibility-weighted Imaging in Thrombolytic Therapy of Acute Ischemic Stroke.
AB  - OBJECTIVE: To provide a comprehensive and latest overview of susceptibility
      weighted imaging (SWI) in the application of thrombolysis in acute ischemic
      stroke, and to update the decision-making effect and clinical value of SWI on
      identifying stroke patients suitable for thrombolytic therapy and possible
      benefits and risks followed. DATA SOURCES: Literatures referred to this review
      were collected from PubMed, Medline, and EMBASE published till May 2017, using
      the search terms including susceptibility-weighted imaging, gradient-echo, T2*,
      thrombolysis, recombinant tissue plasminogen activator (rt-PA), thrombolytic
      therapy, and stroke. STUDY SELECTION: Papers in English or with available English
      abstracts were considered, with no limitation of study design. References were
      also identified from the bibliographies of identified articles and the authors'
      files. RESULTS: SWI is of guiding significance for thrombolytic therapy in stroke
      patients, it can predict the location and length of thrombus and ischemic
      penumbra. It is worthy of noting that susceptibility vessel sign (SVS) on SWI can
      be used to predict recanalization after thrombolytic therapy and whether it is
      better to implement endovascular thrombolectomy in combination or alone. SWI is
      sensitive in detecting cerebral microbleed (CMB), and CMB might not be a
      contraindication for thrombolytic therapy, yet CMBs in multiple foci could
      possibly be related to intracranial hemorrhage (ICH) after thrombolysis. SVS and
      CMB on SWI sequence are of instructive value in performing antiplatelet therapy
      after thrombolytic therapy. Cerebral venous change on SWI is related to lower
      recanalization rate and poor outcome after thrombolysis. CONCLUSIONS: It seems
      that SWI can be applied to guide individualized thrombolytic therapies and assist
      clinicians in making better decisions by weighing benefits and risks. However,
      there still exist controversies about the relationship between signs on SWI and
      thrombolytic therapy.

PMID- 29052574
TI  - Filamin A Gene Associated Periventricular Nodular Heterotopia and Epilepsy in a
      Cohort of Chinese Patients.

PMID- 29052575
TI  - Chylous Ascites and Chylothorax Caused by Constrictive Pericarditis.

PMID- 29052576
TI  - A Tuberous Sclerosis Family with TSC1 (c.1030-1G>A) Mutation Found through a
      Female Presenting as Multiple Ground Glass Nodules in Chest Computed Tomography
      Incidentally.

PMID- 29052577
TI  - Effect of Shen Song Yang Xin Capsule on Myocardial Electrophysiology of Acute
      Atrial Fibrillation in Canine Model.

PMID- 29052578
TI  - Local Panatrophy Associated with Pain: A Rare Variant of Local Panatrophy or a
      New Entity?

PMID- 29052579
TI  - Primary Adrenal Insufficiency Due to Bilateral Adrenal Hematomas in a Patient
      with Primary Antiphospholipid Syndrome.

PMID- 29052580
TI  - A Case of Intracranial Dural Arteriovenous Fistula Mimicking Brainstem Tumor.

PMID- 29052581
TI  - Corrigendum: Efficacy of Real world Entecavir Therapy in Treatment NaiveChronic
      Hepatitis B Patients.
AB  - [This corrects the article DOI: 10.4103/0366-6999.213969.].

PMID- 29052582
TI  - Idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease
      characterized by progressive lung scarring and the histological picture of usual
      interstitial pneumonia (UIP). It is associated with increasing cough and dyspnoea
      and impaired quality of life. IPF affects ~3 million people worldwide, with
      incidence increasing dramatically with age. The diagnostic approach includes the
      exclusion of other interstitial lung diseases or overlapping conditions and
      depends on the identification of the UIP pattern, usually with high-resolution
      CT; lung biopsy might be required in some patients. The UIP pattern is
      predominantly bilateral, peripheral and with a basal distribution of reticular
      changes associated with traction bronchiectasis and clusters of subpleural cystic
      airspaces. The biological processes underlying IPF are thought to reflect an
      aberrant reparative response to repetitive alveolar epithelial injury in a
      genetically susceptible ageing individual, although many questions remain on how
      to define susceptibility. Substantial progress has been made in the understanding
      of the clinical management of IPF, with the availability of two
      pharmacotherapeutic agents, pirfenidone and nintedanib, that decrease
      physiological progression and likely improve progression-free survival. Current
      efforts are directed at identifying IPF early, potentially relying on
      combinations of biomarkers that include circulating factors, demographics and
      imaging data.

PMID- 29052585
TI  - Corrigendum: A Short-Snouted, Middle Triassic Phytosaur and its Implications for
      the Morphological Evolution and Biogeography of Phytosauria.
AB  - This corrects the article DOI: 10.1038/srep46028.

PMID- 29052584
TI  - Corrigendum: A whole-cell tumor vaccine modified to express fibroblast activation
      protein induces antitumor immunity against both tumor cells and cancer-associated
      fibroblasts.
AB  - This corrects the article DOI: 10.1038/srep14421.

PMID- 29052586
TI  - Corrigendum: Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac
      Progenitor Cells.
AB  - This corrects the article DOI: 10.1038/srep17686.

PMID- 29052587
TI  - Corrigendum: Attenuation of Na/K-ATPase Mediated Oxidant Amplification with
      pNaKtide Ameliorates Experimental Uremic Cardiomyopathy.
AB  - This corrects the article DOI: 10.1038/srep34592.

PMID- 29052588
TI  - Corrigendum: Bottom-trawling along submarine canyons impacts deep sedimentary
      regimes.
AB  - This corrects the article DOI: 10.1038/srep43332.

PMID- 29052589
TI  - Obesity: Specialized macrophages contribute to obesity.

PMID- 29052590
TI  - Reversing the tide - diagnosis and prevention of T2DM in populations of African
      descent.
AB  - Populations of African descent are at the forefront of the worldwide epidemic of
      type 2 diabetes mellitus (T2DM). The burden of T2DM is amplified by diagnosis
      after preventable complications of the disease have occurred. Earlier detection
      would result in a reduction in undiagnosed T2DM, more accurate statistics, more
      informed resource allocation and better health. An underappreciated factor
      contributing to undiagnosed T2DM in populations of African descent is that
      screening tests for hyperglycaemia, specifically, fasting plasma glucose and
      HbA1c, perform sub-optimally in these populations. To offset this problem,
      combining tests or adding glycated albumin (a nonfasting marker of glycaemia),
      might be the way forward. However, differences in diet, exercise, BMI,
      environment, gene-environment interactions and the prevalence of sickle cell
      trait mean that neither diagnostic tests nor interventions will be uniformly
      effective in individuals of African, Caribbean or African-American descent. Among
      these three populations of African descent, intensive lifestyle interventions
      have been reported in only the African-American population, in which they have
      been found to provide effective primary prevention of T2DM but not secondary
      prevention. Owing to a lack of health literacy and poor glycaemic control in
      Africa and the Caribbean, customized lifestyle interventions might achieve both
      secondary and primary prevention. Overall, diagnosis and prevention of T2DM
      requires innovative strategies that are sensitive to the diversity that exists
      within populations of African descent.

PMID- 29052592
TI  - Genetics: Towards beta-cell regeneration.

PMID- 29052593
TI  - Diabetes: Predicting severe hypoglycaemia - a step forward.

PMID- 29052594
TI  - Corrigendum: Minimizing the risk of allo-sensitization to optimize the benefit of
      allogeneic cardiac-derived stem/progenitor cells.
AB  - This corrects the article DOI: 10.1038/srep41125.

PMID- 29052591
TI  - Targeting thermogenesis in brown fat and muscle to treat obesity and metabolic
      disease.
AB  - Brown fat is emerging as an interesting and promising target for therapeutic
      intervention in obesity and metabolic disease. Activation of brown fat in humans
      is associated with marked improvement in metabolic parameters such as levels of
      free fatty acids and insulin sensitivity. Skeletal muscle is another important
      organ for thermogenesis, with the capacity to induce energy-consuming futile
      cycles. In this Review, we focus on how these two major thermogenic organs -
      brown fat and muscle - act and cooperate to maintain normal body temperature.
      Moreover, in the light of disease-relevant mechanisms, we explore the molecular
      pathways that regulate thermogenesis in brown fat and muscle. Brown adipocytes
      possess a unique cellular mechanism to convert chemical energy into heat:
      uncoupling protein 1 (UCP1), which can short-circuit the mitochondrial proton
      gradient. However, recent research demonstrates the existence of several other
      energy-expending 'futile' cycles in both adipocytes and muscle, such as creatine
      and calcium cycling. These mechanisms can complement or even substitute for UCP1
      mediated thermogenesis. Moreover, they expand our view of cold-induced
      thermogenesis from a special feature of brown adipocytes to a more general
      physiological principle. Finally, we discuss how thermogenic mechanisms can be
      exploited to expend energy and hence offer new therapeutic opportunities.

PMID- 29052595
TI  - Corrigendum: Hydrogen sulfide-induced itch requires activation of Cav3.2 T-type
      calcium channel in mice.
AB  - This corrects the article DOI: 10.1038/srep16768.

PMID- 29052596
TI  - t(6;11) renal cell carcinoma: a study of seven cases including two with
      aggressive behavior, and utility of CD68 (PG-M1) in the differential diagnosis
      with pure epithelioid PEComa/epithelioid angiomyolipoma.
AB  - Renal cell carcinomas with t(6;11) chromosome translocation involving the TFEB
      gene are indolent neoplasms which often occur in young patients. In this study,
      we report seven cases of renal cell carcinoma with TFEB rearrangement, two of
      whom had histologically proven metastasis. Patients (4F, 3M) ranged in age from
      19 to 55 years (mean 37). One patient developed paratracheal and pleural
      metastases 24 months after surgery and died of disease after 46 months; another
      one recurred with neoplastic nodules in the perinephric fat and pelvic soft
      tissue. Histologically, either cytological or architectural appearance was
      peculiar in each case whereas one tumor displayed the typical biphasic
      morphology. By immunohistochemistry, all tumors labelled for cathepsin K, Melan-A
      and CD68 (KP1 clone). HMB45 and PAX8 staining were detected in six of seven
      tumors. All tumors were negative for CD68 (PG-M1 clone), CKAE1-AE3, CK7, CAIX,
      and AMACR. Seven pure epithelioid PEComa/epithelioid angiomyolipomas, used as
      control, were positive for cathepsin K, melanocytic markers, and CD68 (PG-M1 and
      KP1) and negative for PAX8. Fluorescence in situ hybridization results showed the
      presence of TFEB gene translocation in all t(6;11) renal cell carcinomas with a
      high frequency of split TFEB fluorescent signals (mean 74%). In the primary and
      metastatic samples of the two aggressive tumors, increased gene copy number was
      observed (3-5 fluorescent signals per neoplastic nuclei) with a concomitant
      increased number of CEP6. Review of the literature revealed older age and larger
      tumor size as correlating with aggressive behavior in these neoplasms. In
      conclusion, we present the clinical, morphological and molecular features of
      seven t(6;11) renal cell carcinomas, two with histologically demonstrated
      metastasis. We report the high frequency of split signals by FISH in tumors with
      t(6;11) chromosomal rearrangement and the occurrence of TFEB gene copy number
      gains in the aggressive cases, analyzing either the primary or metastatic tumor.
      Finally, we demonstrate the usefulness of CD68 (PG-M1) immunohistochemical
      staining in distinguishing t(6;11) renal cell carcinoma from pure epithelioid
      PEComa/epithelioid angiomyolipoma.

PMID- 29052597
TI  - SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma.
AB  - Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), formerly known as
      type II enteropathy associated T-cell lymphoma (type II EATL), is a rare,
      aggressive primary intestinal T-cell lymphoma with a poor prognosis and an
      incompletely understood pathogenesis. We collected 40 cases of MEITL and 27 cases
      of EATL, formerly known as type I EATL, and comparatively investigated the T-cell
      receptor (TCR) itself and associated signaling molecules using
      immunohistochemistry, amplicon deep sequencing and bisulfite pyrosequencing. The
      TCR showed both an alphabeta-T-cell origin (30%) and a gammadelta-T-cell
      derivation (55%) resulting in a predominant positive TCR phenotype in MEITL
      compared with the mainly silent TCR phenotype in EATL (65%). The
      immunohistochemical expression of the spleen tyrosine kinase (SYK) turned out to
      be a distinctive feature of MEITL (95%) compared with EATL (0%). Aberrant SYK
      overexpression in MEITL is likely caused by hypomethylation of the SYK promoter,
      while no common mutations in the SYK gene or in its promoter could be detected.
      Using amplicon deep sequencing, mutations in DNMT3A, IDH2, and TET2 were
      infrequent events in MEITL and EATL. Immunohistochemical expression of linker for
      activation of T-cells (LAT) subdivided MEITL into a LAT expressing subset (33%)
      and a LAT silent subset (67%) with a potentially earlier disease onset in LAT
      positive MEITL.

PMID- 29052598
TI  - Association between clinicopathological characteristics and RAS mutation in
      colorectal cancer.
AB  - In colorectal cancer, KRAS (exons 2, 3, and 4) and NRAS (exons 2, 3, and 4)
      mutations are associated with resistance to antiepidermal growth factor receptor
      monoclonal antibodies, and BRAF mutation is a molecular marker of poor prognosis.
      KRAS exon 2 and BRAF-mutated colorectal cancers have well-known distinct
      clinicopathological characteristics. Comparison of tumors with different RAS
      status (exons 2, 3, and 4 of KRAS and NRAS) based on their clinicopathological
      characteristics has never been established. All colorectal cancer patients with
      RAS and BRAF testing from 2011 to 2015 were included in this observational
      retrospective study. Patient and tumor characteristics were collected and
      correlation with RAS and BRAF status was evaluated. A total of 1735 patients with
      colorectal cancer were included. RAS-mutated colorectal cancers (n=1002),
      compared with RAS wild-type colorectal cancers (n=733), were significantly
      associated with male gender, classical adenocarcinoma subtype, well/moderately
      differentiated tumors, and microsatellite stable phenotype. KRAS codon 13-mutated
      colorectal cancers (n=171), compared with RAS wild-type colorectal cancers, more
      frequently presented classical adenocarcinoma subtype and microsatellite stable
      phenotype. In comparison with other RAS mutations, KRAS exon 3-mutated colorectal
      cancers (n=23) were associated with mucinous/rare histological subtypes and, most
      likely to located in the rectum. KRAS exon 4-mutated colorectal cancers (n=33)
      were more frequently associated with mucinous/rare histological subtypes. There
      was no significant association between NRAS mutation (n=37) and
      clinicopathological features. Colorectal cancers are associated with different
      clinicopathological features according to the type of RAS mutation. Consequently,
      these particular characteristics must be considered when assessing the prognostic
      value of RAS status in colorectal cancer.

PMID- 29052599
TI  - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a
      review for pathologists.
AB  - The rising incidence of papillary thyroid carcinoma is linked in part to
      inclusion of noninvasive follicular variant of papillary thyroid carcinoma.
      Despite its designation as carcinoma, noninvasive follicular variant of papillary
      thyroid carcinoma appears to be exceptionally indolent, often over treated by
      current treatment practices. Additionally, criteria for diagnosis have
      historically been subjective and challenging. Recently, an international
      multidisciplinary collaborative group performed a clinicopathologic survey of
      such cases with extended follow-up and concluded based on the outcome data that a
      revision in nomenclature was warranted, proposing 'Noninvasive Follicular Thyroid
      Neoplasm with Papillary-like Nuclear Features (NIFTP).' This monograph is a
      synopsis and guide for pathologists on NIFTP and focuses on histologic features,
      including inclusion and exclusion criteria used to define NIFTP, as well as
      grossing guidelines, reporting practices, and potential diagnostic limitations.

PMID- 29052600
TI  - Ultrasensitive automated RNA in situ hybridization for kappa and lambda light
      chain mRNA detects B-cell clonality in tissue biopsies with performance
      comparable or superior to flow cytometry.
AB  - The assessment of B-cell clonality is a critical component of the evaluation of
      suspected lymphoproliferative disorders, but analysis from formalin-fixed,
      paraffin-embedded tissues can be challenging if fresh tissue is not available for
      flow cytometry. Immunohistochemical and conventional bright field in situ
      hybridization stains for kappa and lambda are effective for evaluation of plasma
      cells but are often insufficiently sensitive to detect the much lower abundance
      of light chains present in B-cells. We describe an ultrasensitive RNA in situ
      hybridization assay that has been adapted for use on an automated
      immunohistochemistry platform and compare results with flow cytometry in 203
      consecutive tissues and 104 consecutive bone marrows. Overall, in 203 tissue
      biopsies, RNA in situ hybridization identified light chain-restricted B-cells in
      85 (42%) vs 58 (29%) by flow cytometry. Within 83 B-cell non-Hodgkin lymphomas,
      RNA in situ hybridization identified restricted B-cells in 74 (89%) vs 56 (67%)
      by flow cytometry. B-cell clonality could be evaluated in only 23/104 (22%) bone
      marrow cases owing to poor RNA preservation, but evaluable cases showed 91%
      concordance with flow cytometry. RNA in situ hybridization allowed for
      recognition of biclonal/composite lymphomas not identified by flow cytometry and
      highlighted unexpected findings, such as coexpression of kappa and lambda RNA in
      2 cases and the presence of lambda light chain RNA in a T lymphoblastic lymphoma.
      Automated RNA in situ hybridization showed excellent interobserver
      reproducibility for manual evaluation (average K=0.92), and an automated image
      analysis system showed high concordance (97%) with manual evaluation. Automated
      RNA in situ hybridization staining, which can be adopted on commonly utilized
      immunohistochemistry instruments, allows for the interpretation of clonality in
      the context of the morphological features in formalin-fixed, paraffin-embedded
      tissues with a clinical sensitivity similar or superior to flow cytometry.

PMID- 29052601
TI  - Intratubular amyloid in light chain cast nephropathy is a risk factor for
      systemic light chain amyloidosis.
AB  - Light chain cast nephropathy is the most common form of kidney disease in
      patients with multiple myeloma. Light chain casts may occasionally show amyloid
      staining properties, that is, green birefringence after Congo red staining. The
      frequency and clinical significance of this intratubular amyloid are poorly
      understood. Here, we retrospectively assessed the clinicopathological features of
      60 patients with histologically proven light chain cast nephropathy with a
      specific emphasis on intratubular amyloid, especially, its association with
      extrarenal systemic light chain amyloidosis. We found intratubular amyloid in 17
      cases (17/60, 28%) and it was more frequent in patients with lambda light chain
      gammopathy (13/17 in the 'intratubular amyloid' group vs 19/43 in the 'no
      intratubular amyloid' group, P=0.02). Pathological examination of extrarenal
      specimens showed that intratubular amyloid was significantly associated with the
      occurrence of systemic light chain amyloidosis (5/13 in the 'intratubular
      amyloid' group vs 0/30 in the 'no intratubular amyloid' group, P=0.001). Our
      results indicate that first, intratubular amyloid is not a rare finding in kidney
      biopsies of patients with light chain cast nephropathy, and, second, it reflects
      an amyloidogenic capacity of light chains that can manifest as systemic light
      chain amyloidosis. Thus, intratubular amyloid should be systematically screened
      for in kidney biopsies from patients with light chain cast nephropathy and, if
      detected, should prompt a work-up for associated systemic light chain
      amyloidosis.

PMID- 29052603
TI  - Response to 'About bariatric surgery and diabetic retinopathy; the debate
      continues'.

PMID- 29052602
TI  - MTBDRplus for the rapid diagnosis of ocular tuberculosis and screening of drug
      resistance.
AB  - PurposeTimely diagnosis of intraocular tuberculosis (IOTB) along with detection
      of drug resistance can save many eyes from visual impairment. With the growing
      incidence of IOTB and rising drug resistance, a reliable diagnostic platform for
      simultaneous detection of the agent and mutated gene is urgently needed. The
      MTBDRplus assay was evaluated directly on vitreous fluid samples for the
      same.Patients and methodsIn a prospective study, The MTBDRplus assay was
      performed on 127 vitreous fluid samples (77 'study group' comprising cases of
      presumed ocular tuberculosis and 50 'control group' cases of disease controls
      (n=25) and non-uveitic controls (n=25)). All samples positive by MTBDRplus assay
      were subjected to gene sequencing to confirm the mutations for rifampicin and
      isoniazid resistance.ResultsThe MTBDRplus assay produced a sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      of 36.36%, 100%, 100%, and 50.50%, respectively, for the detection of IOTB. Among
      the 28 cases from study group that were positive by MTBDRplus assay, rifampicin
      resistance was reported in six and isoniazid resistance in two cases. On
      sequencing of rpoB and katG gene, one case of false rifampicin-resistant by
      MTBDRplus was found. The other resistant isolates showed concordant mutations
      between MTBDRplus assay and sequencing.ConclusionThe MTBDRplus assay is an
      effective tool for the rapid diagnosis of IOTB along with detection of drug
      resistance, thereby improving the outcome in IOTB.

PMID- 29052604
TI  - Effect of topical loteprednol etabonate with lid hygiene on tear cytokines and
      meibomian gland dysfunction in prosthetic eye wearers.
AB  - PurposeTo assess tear cytokine levels and clinical outcomes in meibomian gland
      dysfunction (MGD) in the blind eye of patients wearing an ocular prosthesis after
      2 months of treatment with topical loteprednol etabonate and eyelid scrubs with
      warm compresses.Patients and methodsThis study included patients with MGD wearing
      a unilateral ocular prosthesis for more than 1 year. All patients topically
      received 0.5% loteprednol etabonate and were instructed to scrub their eyelids
      with warm compresses on the prosthetic eye for 2 months. We evaluated tear
      cytokine levels using Multiplex Bead Immunoassays, performed biomicroscopic
      examination of the lid margins and meibomian gland, conducted meibography
      imaging, and assessed MGD-related ocular symptoms using a questionnaire for the
      prosthetic eye before and 2 months after treatment.ResultsThirty consecutive
      patients were included. There were significant reductions in the levels of
      interleukin (IL)-6, interferon-gamma, monocyte chemotactic protein-1, IL-8, tumor
      necrosis factor-alpha, and IL-1beta (P<0.001 for each cytokine). Moreover, there
      were improvements in ocular symptoms (P=0.001), lid margin abnormalities
      (P<0.001), meibomian gland expressibility (P<0.001) and meibography findings
      (P=0.037).ConclusionTopical loteprednol etabonate in conjunction with eyelid
      scrubs and warm compresses were effective in treating MGD in prosthetic eye
      wearers. Furthermore, tear cytokine measurements may serve as an additional
      approach for evaluating the efficacy of anti-inflammatory treatment for MGD in
      prosthetic eye wearers.

PMID- 29052605
TI  - Holi colors and chemical contact keratitis.

PMID- 29052606
TI  - The evolution of eyes: major steps. The Keeler lecture 2017: centenary of Keeler
      Ltd.
AB  - Ocular evolution is an immense topic, and I do not expect to cover all the
      details of this process in this manuscript. I will present some concepts about
      some of the major steps in the evolutionary process to stimulate your thinking
      about this interesting and complex topic. In the prebiotic soup, vision was not
      inevitable. Eyes were not preordained. Nor were their shapes, sizes, or current
      physiology. Sight is an evolutionary gift but it was not ineluctable. The
      existence of eyes is so basic to our profession that we often do not consider how
      and why vision appeared or evolved on earth at all. Although vision is a
      principal sensory modality for at least three major phyla and is present in three
      or four more phyla, there are other sensory mechanisms that could have been and
      were occasionally selected instead. Some animals rely on other sensory mechanisms
      such as audition, echolocation, or olfaction that are much more effective in
      their particular niche than would be vision. We may not believe those sensory
      mechanisms to be as robust as vision, but the creatures using those skills would
      argue otherwise. Why does vision exist at all? And why is it so dominant at least
      in the number of species that rely upon it for their principal sensory mechanism?
      How did vision begin? What were the important steps in the evolution of eyes? How
      did eyes differentiate along their various paths, and why?

PMID- 29052607
TI  - Emergency therapeutic penetrating keratoplasty in a tertiary ophthalmic care
      facility.

PMID- 29052608
TI  - A novel and faster method of manual grading to measure choroidal thickness using
      optical coherence tomography.
AB  - PurposeChoroidal thickness (CT) measurements are typically obtained from manual
      segmentation of optical coherence tomography (OCT) B-scans. This method is time
      consuming. We aimed to describe a novel and faster technique to obtain CT
      measurements.Patients and methodsIn a prospective cohort study of 200 healthy
      eyes, Spectral-Domain OCT with enhanced depth imaging were performed with the
      Spectralis OCT using standardised imaging protocols. The OCT scans were
      independently graded by reading centre-certified graders. The standard method of
      manual adjustment of segmentation boundaries was performed. The new method
      consisted of adjusting the lower segmentation line to the choroid-scleral
      boundary to generate the combined choroid-retina thickness, and subtracting the
      original retinal thickness (RT) from it to measure CT. Mean CT in the respective
      Early Treatment Diabetic Retinopathy Study (ETDRS) subfields was measured via the
      two methods, and were compared with intraclass correlation coefficients (ICC) and
      Bland-Altman plots.ResultsThe mean central subfield CT was 324.4 MUm using the
      original method, compared with 328.8 MUm using the new method, with a mean
      difference of 4.5 MUm (range: -14.0 to +4.0 MUm; P<0.001), and ICC for agreement
      of 0.9996 (P<0.001). Similar comparability was achieved for mean CT across other
      ETDRS subfields, with mean differences ranging from 2.4 to 3.7 MUm, and ICCs
      ranging from 0.9993 to 0.9995 (all P<0.001).ConclusionsMean CT can be measured by
      subtracting the original RT from the combined choroid-retina thickness. Only one
      segmentation line needs to be adjusted, instead of two, reducing time required
      for segmentation. This method is faster and reliable.

PMID- 29052610
TI  - Reply to: 'Comment on: 'One-year real-world outcomes in patients receiving fixed
      dosing aflibercept for neovascular age-related macular degeneration'.

PMID- 29052611
TI  - Amyotrophic lateral sclerosis.
AB  - This corrects the article DOI: 10.1038/nrdp.2017.71.

PMID- 29052612
TI  - Erratum: An exactly solvable, spatial model of mutation accumulation in cancer.
AB  - This corrects the article DOI: 10.1038/srep39511.

PMID- 29052609
TI  - Neuro-ophthalmic side effects of molecularly targeted cancer drugs.
AB  - The past two decades has been an amazing time in the advancement of cancer
      treatment. Molecularly targeted therapy is a concept in which specific cellular
      molecules (overexpressed, mutationally activated, or selectively expressed
      proteins) are manipulated in an advantageous manner to decrease the
      transformation, proliferation, and/or survival of cancer cells. In addition,
      increased knowledge of the role of the immune system in carcinogenesis has led to
      the development of immune checkpoint inhibitors to restore and enhance cellular
      mediated antitumor immunity. The United States Food and Drug Administration
      approval of the chimeric monoclonal antibody (mAb) rituximab in 1997 for the
      treatment of B cell non-Hodgkin lymphoma ushered in a new era of targeted therapy
      for cancer. A year later, trastuzumab, a humanized mAb, was approved for patients
      with breast cancer. In 2001, imatinib was the first small-molecule kinase
      inhibitor approved. The approval of ipilimumab-the first in class immune
      checkpoint inhibitor-in 2011 serves as a landmark period of time in the
      resurgence of immunotherapy for cancer. Despite the notion that increased tumor
      specificity results in decreased complications, toxicity remains a major hurdle
      in the development and implementation of many of the targeted anticancer drugs.
      This article will provide an overview of the current cellular and immunological
      understanding of cancer pathogenesis-the foundation upon which molecularly
      targeted therapies were developed-and a description of the ocular and neuro
      ophthalmic toxicity profile of mAbs, immune checkpoint inhibitors, and small
      molecule kinase inhibitors.

PMID- 29052613
TI  - Dynorphin Counteracts Orexin in the Paraventricular Nucleus of the Thalamus:
      Cellular and Behavioral Evidence.
AB  - The orexin (Orx) system plays a critical role in drug addiction and reward
      related behaviors. The dynorphin (Dyn) system promotes depressive-like behavior
      and plays a key role in the aversive effects of stress. Orx and Dyn are co
      released and have opposing functions in reward and motivation in the ventral
      tegmental area (VTA). Previous studies suggested that OrxA transmission in the
      posterior paraventricular nucleus of the thalamus (pPVT) participates in cocaine
      seeking behavior. This study determined whether Orx and Dyn interact in the pPVT.
      Using the brain slice preparation for cellular recordings, superfusion of DynA
      onto pPVT neurons decreased the frequency of spontaneous and miniature excitatory
      postsynaptic currents (s/mEPSCs). OrxA increased the frequency of sEPSCs but had
      no effect on mEPSCs, suggesting a network-driven effect of OrxA. The amplitudes
      of s/mEPSCs were unaffected by the peptides, indicating a presynaptic action on
      glutamate release. Augmentation of OrxA-induced glutamate release was reversed by
      DynA. Utilizing a behavioral approach, separate groups of male Wistar rats were
      trained to self-administer cocaine or sweetened condensed milk (SCM). After
      extinction, rats received intra-pPVT administration of OrxA+/-DynA+/-the kappa
      opioid receptor antagonist nor-binaltorphimine (NorBNI) under extinction
      conditions. OrxA reinstated cocaine- and SCM-seeking behavior, with a greater
      effect in cocaine animals. DynA blocked OrxA-induced cocaine seeking but not SCM
      seeking. NorBNI did not induce or potentiate cocaine-seeking behavior induced by
      OrxA but reversed DynA effect. This indicates that the kappa-opioid system in the
      pPVT counteracts OrxA-induced cocaine seeking, suggesting a novel therapeutic
      target to prevent cocaine relapse.

PMID- 29052614
TI  - Narp Mediates Antidepressant-Like Effects of Electroconvulsive Seizures.
AB  - Growing recognition of persistent cognitive defects associated with
      electroconvulsive therapy (ECT), a highly effective and commonly used
      antidepressant treatment, has spurred interest in identifying its mechanism of
      action to guide development of safer treatment options. However, as repeated
      seizure activity elicits a bewildering array of electrophysiological and
      biochemical effects, this goal has remained elusive. We have examined whether
      deletion of Narp, an immediate early gene induced by electroconvulsive seizures
      (ECS), blocks its antidepressant efficacy. Based on multiple measures, we infer
      that Narp knockout mice undergo normal seizure activity in this paradigm, yet
      fail to display antidepressant-like behavioral effects of ECS. Although Narp
      deletion does not suppress ECS-induced proliferation in the dentate gyrus, it
      blocks dendritic outgrowth of immature granule cell neurons in the dentate
      molecular layer induced by ECS. Taken together, these findings indicate that Narp
      contributes to the antidepressant action of ECT and implicate the ability of ECS
      to induce dendritic arborization of differentiating granule cells as a relevant
      step in eliciting this response.

PMID- 29052615
TI  - Effects of Alcohol Abuse on Proliferating Cells, Stem/Progenitor Cells, and
      Immature Neurons in the Adult Human Hippocampus.
AB  - In animal studies, impaired adult hippocampal neurogenesis is associated with
      behavioral pathologies including addiction to alcohol. We hypothesize that
      alcohol abuse may have a detrimental effect on the neurogenic pool of the dentate
      gyrus in the human hippocampus. In this study we investigate whether alcohol
      abuse affects the number of proliferating cells, stem/progenitor cells, and
      immature neurons in samples from postmortem human hippocampus. The specimens were
      isolated from deceased donors with an on-going alcohol abuse, and from controls
      with no alcohol overconsumption. Mid-hippocampal sections were immunostained for
      Ki67, a marker for cell proliferation, Sox2, a stem/progenitor cell marker, and
      DCX, a marker for immature neurons. Immunoreactivity was counted in alcoholic
      subjects and compared with controls. Counting was performed in the three layers
      of dentate gyrus: the subgranular zone, the granular cell layer, and the
      molecular layer. Our data showed reduced numbers of all three markers in the
      dentate gyrus in subjects with an on-going alcohol abuse. This reduction was most
      prominent in the subgranular zone, and uniformly distributed across the distances
      from the granular cell layer. Furthermore, alcohol abusers showed a more
      pronounced reduction of Sox2-IR cells than DCX-IR cells, suggesting that alcohol
      primarily causes a depletion of the stem/progenitor cell pool and that immature
      neurons are secondarily affected. These results are in agreement with
      observations of impaired adult hippocampal neurogenesis in animal studies and
      lend further support for the association between hippocampal dysfunction and
      alcohol abuse.

PMID- 29052617
TI  - ADHD, Smoking Withdrawal, and Inhibitory Control: Results of a Neuroimaging Study
      with Methylphenidate Challenge.
AB  - Smoking withdrawal negatively impacts inhibitory control, and these effects are
      greater for smokers with preexisting attention problems, such as attention
      deficit/hyperactivity disorder (ADHD). The current study preliminarily evaluated
      changes in inhibitory control-related behavior and brain activation during
      smoking withdrawal among smokers with ADHD. Moreover, we investigated the role of
      catecholamine transmission in these changes by examining the effects of 40 mg
      methylphenidate (MPH) administration. Adult daily smokers with (n=17) and without
      (n=20) ADHD completed fMRI scanning under each of three conditions: (a) smoking
      as usual+placebo; (b) 24 h smoking abstinence+placebo and (c) 24 h smoking
      abstinence+MPH. Scan order was randomized and counterbalanced. Participants
      completed a modified Go/No-Go task to assess both sustained and transient
      inhibitory control. Voxelwise analysis of task-related BOLD signal revealed a
      significant group-by-abstinence interaction in occipital/parietal cortex during
      sustained inhibition, with greater abstinence-induced decreases in activation
      observed among ADHD smokers compared with non-ADHD smokers. Changes in behavioral
      performance during abstinence were associated with changes in activation in
      regions of occipital and parietal cortex and bilateral insula during sustained
      inhibition in both groups. MPH administration improved behavioral performance and
      increased sustained inhibitory control-related activation for both groups. During
      transient inhibition, MPH increased prefrontal activation for both groups and
      increased striatal activation only among ADHD smokers. These preliminary findings
      suggest that abstinence-induced changes in catecholamine transmission in visual
      attention areas (eg, occipital and superior parietal cortex) may be associated
      with inhibitory control deficits and contribute to smoking vulnerability among
      individuals with ADHD.

PMID- 29052616
TI  - Pregenual Anterior Cingulate Dysfunction Associated with Depression in OCD: An
      Integrated Multimodal fMRI/1H MRS Study.
AB  - Depression is a commonly occurring symptom in obsessive-compulsive disorder
      (OCD), and is associated with worse functional impairment, poorer quality of
      life, and poorer treatment response. Understanding the underlying neurochemical
      and connectivity-based brain mechanisms of this important symptom domain in OCD
      is necessary for development of novel, more globally effective treatments. To
      investigate biopsychological mechanisms of comorbid depression in OCD, we
      examined effective connectivity and neurochemical signatures in the pregenual
      anterior cingulate cortex (pACC), a structure known to be involved in both OCD
      and depression. Resting-state functional magnetic resonance imaging (fMRI) and 1H
      magnetic resonance spectroscopy (MRS) data were obtained from participants with
      OCD (n=49) and healthy individuals of equivalent age and sex (n=25). Granger
      causality-based effective (directed) connectivity was used to define causal
      networks involving the right and left pACC. The interplay between fMRI
      connectivity, 1H MRS and clinical data was explored by applying moderation and
      mediation analyses. We found that the causal influence of the right dorsal
      anterior midcingulate cortex (daMCC) on the right pACC was significantly lower in
      the OCD group and showed significant correlation with depressive symptom severity
      in the OCD group. Lower and moderate levels of glutamate (Glu) in the right pACC
      significantly moderated the interaction between right daMCC-pACC connectivity and
      depression severity. Our results suggest a biochemical-connectivity-psychological
      model of pACC dysfunction contributing to depression in OCD, particularly
      involving intracingulate connectivity and glutamate levels in the pACC. These
      findings have implications for potential molecular and network targets for
      treatment of this multi-faceted psychiatric condition.

PMID- 29052618
TI  - A Role for Prefrontal Cortical NMDA Receptors in Murine Alcohol-Heightened
      Aggression.
AB  - Alcohol is associated with nearly half of all violent crimes committed in the
      United States; yet, a potential neural basis for this type of pathological
      aggression remains elusive. Alcohol may act on N-methyl-d-aspartate receptors
      (NMDARs) within cortical circuits to impede processing and to promote aggression.
      Here, male mice were characterized as alcohol-heightened (AHAs) or alcohol non
      heightened aggressors (ANAs) during resident-intruder confrontations after self
      administering 1.0 g/kg alcohol (6% w/v) or water. Alcohol produced a pathological
      like pattern of aggression in AHAs; these mice shifted their bites to more
      vulnerable locations on the body of a submissive animal, including the anterior
      back and ventrum after consuming alcohol. In addition, through immunoblotting, we
      found that AHAs overexpressed the NMDAR GluN2D subunit in the prefrontal cortex
      (PFC) as compared to ANAs while the two phenotypes expressed similar levels of
      GluN1, GluN2A and GluN2B. After identifying several behavioral and molecular
      characteristics that distinguish AHAs from ANAs, we tested additional mice for
      their aggression following preferential antagonism of GluN2D-containing NMDARs.
      In these experiments, groups of AHAs and ANAs self-administered 1.0 g/kg alcohol
      (6% w/v) or water before receiving intraperitoneal (i.p.) doses of ketamine or
      memantine, or infusions of memantine directly into the prelimbic (PLmPFC) or
      infralimbic medial PFC (ILmPFC). Moderate doses of IP ketamine, IP memantine, or
      intra-PLmPFC memantine increased aggression in AHAs, but only in the absence of
      alcohol. Prior alcohol intake blocked the pro-aggressive effects of ketamine or
      memantine. In contrast, only memantine, administered systemically or intra
      PLmPFC, interacted with prior alcohol intake to escalate aggression in ANAs.
      Intra-ILmPFC memantine had no effect on aggression in either AHAs or ANAs. In
      sum, this work illustrates a potential role of GluN2D-containing NMDARs in the
      PLmPFC in alcohol-heightened aggression. GluN2D-containing NMDARs are highly
      expressed on cortical parvalbumin-containing interneurons, suggesting that, in a
      subset of individuals, alcohol may functionally alter signal integration within
      cortical microcircuits to dysregulate threat reactivity and promote aggression.
      This work suggests that targeting GluN2D-NMDARs may be of use in reducing the
      impact of alcohol-related violence in the human population.

PMID- 29052620
TI  - Solving a Higgs optimization problem with quantum annealing for machine learning.
AB  - The discovery of Higgs-boson decays in a background of standard-model processes
      was assisted by machine learning methods. The classifiers used to separate
      signals such as these from background are trained using highly unerring but not
      completely perfect simulations of the physical processes involved, often
      resulting in incorrect labelling of background processes or signals (label noise)
      and systematic errors. Here we use quantum and classical annealing (probabilistic
      techniques for approximating the global maximum or minimum of a given function)
      to solve a Higgs-signal-versus-background machine learning optimization problem,
      mapped to a problem of finding the ground state of a corresponding Ising spin
      model. We build a set of weak classifiers based on the kinematic observables of
      the Higgs decay photons, which we then use to construct a strong classifier. This
      strong classifier is highly resilient against overtraining and against errors in
      the correlations of the physical observables in the training data. We show that
      the resulting quantum and classical annealing-based classifier systems perform
      comparably to the state-of-the-art machine learning methods that are currently
      used in particle physics. However, in contrast to these methods, the annealing
      based classifiers are simple functions of directly interpretable experimental
      parameters with clear physical meaning. The annealer-trained classifiers use the
      excited states in the vicinity of the ground state and demonstrate some advantage
      over traditional machine learning methods for small training datasets. Given the
      relative simplicity of the algorithm and its robustness to error, this technique
      may find application in other areas of experimental particle physics, such as
      real-time decision making in event-selection problems and classification in
      neutrino physics.

PMID- 29052621
TI  - Cancer treatment: Bacterial snack attack deactivates a drug.

PMID- 29052622
TI  - PhD students: living wage key to diversity.

PMID- 29052623
TI  - Ornithology: Danish dairy farmer delivers data coup.

PMID- 29052624
TI  - Open data: Spot data glitches before publication.

PMID- 29052625
TI  - A parts-per-billion measurement of the antiproton magnetic moment.
AB  - Precise comparisons of the fundamental properties of matter-antimatter conjugates
      provide sensitive tests of charge-parity-time (CPT) invariance, which is an
      important symmetry that rests on basic assumptions of the standard model of
      particle physics. Experiments on mesons, leptons and baryons have compared
      different properties of matter-antimatter conjugates with fractional
      uncertainties at the parts-per-billion level or better. One specific quantity,
      however, has so far only been known to a fractional uncertainty at the parts-per
      million level: the magnetic moment of the antiproton, . The extraordinary
      difficulty in measuring with high precision is caused by its intrinsic smallness;
      for example, it is 660 times smaller than the magnetic moment of the positron.
      Here we report a high-precision measurement of in units of the nuclear magneton
      MUN with a fractional precision of 1.5 parts per billion (68% confidence level).
      We use a two-particle spectroscopy method in an advanced cryogenic multi-Penning
      trap system. Our result  = -2.7928473441(42)MUN (where the number in parentheses
      represents the 68% confidence interval on the last digits of the value) improves
      the precision of the previous best measurement by a factor of approximately 350.
      The measured value is consistent with the proton magnetic moment, MUp =
      2.792847350(9)MUN, and is in agreement with CPT invariance. Consequently, this
      measurement constrains the magnitude of certain CPT-violating effects to below
      1.8 * 10-24 gigaelectronvolts, and a possible splitting of the proton-antiproton
      magnetic moments by CPT-odd dimension-five interactions to below 6 * 10-12 Bohr
      magnetons.

PMID- 29052628
TI  - PhD students: side jobs are no solution.

PMID- 29052631
TI  - Artificial intelligence: Learning to play Go from scratch.

PMID- 29052630
TI  - Mastering the game of Go without human knowledge.
AB  - A long-standing goal of artificial intelligence is an algorithm that learns,
      tabula rasa, superhuman proficiency in challenging domains. Recently, AlphaGo
      became the first program to defeat a world champion in the game of Go. The tree
      search in AlphaGo evaluated positions and selected moves using deep neural
      networks. These neural networks were trained by supervised learning from human
      expert moves, and by reinforcement learning from self-play. Here we introduce an
      algorithm based solely on reinforcement learning, without human data, guidance or
      domain knowledge beyond game rules. AlphaGo becomes its own teacher: a neural
      network is trained to predict AlphaGo's own move selections and also the winner
      of AlphaGo's games. This neural network improves the strength of the tree search,
      resulting in higher quality move selection and stronger self-play in the next
      iteration. Starting tabula rasa, our new program AlphaGo Zero achieved superhuman
      performance, winning 100-0 against the previously published, champion-defeating
      AlphaGo.

PMID- 29052633
TI  - Computer science: Data analysis meets quantum physics.

PMID- 29052632
TI  - Social behaviour shapes hypothalamic neural ensemble representations of
      conspecific sex.
AB  - All animals possess a repertoire of innate (or instinctive) behaviours, which can
      be performed without training. Whether such behaviours are mediated by
      anatomically distinct and/or genetically specified neural pathways remains
      unknown. Here we report that neural representations within the mouse
      hypothalamus, that underlie innate social behaviours, are shaped by social
      experience. Oestrogen receptor 1-expressing (Esr1+) neurons in the ventrolateral
      subdivision of the ventromedial hypothalamus (VMHvl) control mating and fighting
      in rodents. We used microendoscopy to image Esr1+ neuronal activity in the VMHvl
      of male mice engaged in these social behaviours. In sexually and socially
      experienced adult males, divergent and characteristic neural ensembles
      represented male versus female conspecifics. However, in inexperienced adult
      males, male and female intruders activated overlapping neuronal populations. Sex
      specific neuronal ensembles gradually separated as the mice acquired social and
      sexual experience. In mice permitted to investigate but not to mount or attack
      conspecifics, ensemble divergence did not occur. However, 30 minutes of sexual
      experience with a female was sufficient to promote the separation of male and
      female ensembles and to induce an attack response 24 h later. These observations
      uncover an unexpected social experience-dependent component to the formation of
      hypothalamic neural assemblies controlling innate social behaviours. More
      generally, they reveal plasticity and dynamic coding in an evolutionarily ancient
      deep subcortical structure that is traditionally viewed as a 'hard-wired' system.

PMID- 29052634
TI  - Federal funding: Stifled by budgets, not irrelevance.

PMID- 29052636
TI  - Give researchers a lifetime word limit.

PMID- 29052637
TI  - Reboot for the AI revolution.

PMID- 29052638
TI  - The second Renaissance.

PMID- 29052639
TI  - FDA advisers back gene therapy for rare form of blindness.

PMID- 29052641
TI  - Colliding stars spark rush to solve cosmic mysteries.

PMID- 29052640
TI  - Trump EPA begins push to overturn Obama-era climate regulation.

PMID- 29052642
TI  - Science must examine the future of work.

PMID- 29052643
TI  - New definitions of scientific units are on the horizon.

PMID- 29052644
TI  - Epic star collision, asteroid fly-by and journal resignations.

PMID- 29052645
TI  - The future of work.

PMID- 29052646
TI  - Blue is in the eye of the bee-holder.

PMID- 29052647
TI  - Eye in the sky offers clearest vision of Earth.

PMID- 29052648
TI  - Lessons from history for the future of work.

PMID- 29052649
TI  - The shape of work to come.

PMID- 29052650
TI  - Japanese research leaders warn about national science decline.

PMID- 29052651
TI  - Activity of daily living on non-working and working days in Polish urban society.
AB  - OBJECTIVES: Activities of daily living are currently the simplest form of
      activity. For many people this is the only activity in which they participate. In
      this connection, it is important to determine the level of physical activity
      connected with daily habits including occupational activities. The main goal of
      the presented study has been to assess the level of activities of daily living in
      different age groups and its differentiation by season and working (WD) and non
      working days (NWD). MATERIAL AND METHODS: The study group (urban citizens, N =
      106) was divided into young (Y) (N = 40), middle-aged (M) (N = 38), and senior
      (S) (N = 28) participants. The daily step number on 7 consecutive days during 4
      seasons between June 2012 and 2013 was counted objectively using pedometers. The
      long-form of the International Physical Activity Questionnaire (IPAQ) was
      completed each season as a subjective assessment. RESULTS: The daily step number
      for the whole group for the year was (median) 6615 (range: 3648-10 709), fewer
      than recommended. The median (Me) was highest in group M (Me = 6994, range: 3648
      10 709) followed by Y (Me = 6957, range: 4094-10 321) and S (Me = 5469, range:
      3743-8955). The lowest daily step number occurred in winter (M = 6208, Y = 6063,
      S = 5242), and the highest in spring (Y = 7385) or summer (M = 7717; S = 6095).
      All groups had a greater daily step number on WDs compared to NWDs (Y: 8411 vs.
      5744, M: 7612 vs. 5839, S: 6327 vs. 4580; p < 0.01 for all). Pedometer-tracked
      values did not correlate with the IPAQ results. CONCLUSIONS: Activity level in
      Polish urban society is low, especially on NWDs and in colder months. The daily
      number of steps is highest in the middle-aged group, which may be connected with
      working status. Objective methods are recommended for assessing physical activity
      level. Int J Occup Med Environ Health 2018;31(1):47-54.

PMID- 29052652
TI  - Types of work-related behavior and experiences and stress coping strategies among
      single mothers and mothers in relationships differentiating role of work
      satisfaction.
AB  - OBJECTIVES: The purpose of the study has been to describe functioning of single
      and mothers in relationships (married or in informal relationships) at work and
      verify if the declared degree of work satisfaction differentiates types of
      behavior at work and stress coping strategies in both groups of mothers. MATERIAL
      AND METHODS: The study was conducted on equal samples of single mothers (N = 186)
      and mothers from 2-parent families (N = 186) using Latack Coping Scale that
      measures work-related stress coping strategies, the AVEM (Arbeitsbezogenes
      Verhaltens- und Erlebensmuster - Work-Related Behavior and Experience Pattern)
      questionnaire, and a survey. It showed similarity between the studied groups in
      terms of the measured variables. RESULTS: There were considerable differences
      between single and married mothers in terms of support seeking strategies. The
      interaction of work satisfaction and the type of motherhood significantly
      differentiates (p = 0.03) the avoidance strategy of resignation. CONCLUSIONS:
      That strategy of resignation was more frequently used by single mothers with
      lower work satisfaction, who were distinctly different from those whose work
      satisfaction was higher, and from the mothers in relationships (married or in
      informal relationships) (regardless of the level of their work satisfaction). Int
      J Occup Med Environ Health 2018;31(1):55-69.

PMID- 29052653
TI  - Distinct Trajectories of Fatigue and Sleep Disturbance in Women Receiving
      Chemotherapy for Breast Cancer.
AB  - PURPOSE/OBJECTIVES: To examine self-reported severity of fatigue and disturbed
      sleep experienced daily by women with breast cancer during multiple cycles of
      chemotherapy, exploring potential classes of women experiencing similar symptom
      trajectories.?. DESIGN: In a secondary analysis, classes of women experiencing
      similar patterns of fatigue and disturbed sleep were identified.?. SETTING:
      Oncology clinics in the United States.?. SAMPLE: 166 women with breast cancer
      receiving chemotherapy. ?. METHODS: Severity scores were self-reported daily
      using an automated system. Classes of fatigue and disturbed sleep severity were
      identified using latent growth mixture modeling.?. MAIN RESEARCH VARIABLES:
      Fatigue, disturbed sleep, age, stage of disease, education, employment, marital
      status, chemotherapy regimen, hours lying down, and missed work.?. FINDINGS:
      Three fatigue classes were identified. CONCLUSIONS: Patterns of symptom
      trajectories for fatigue and disturbed sleep were distinguished by baseline
      symptom severity.?. IMPLICATIONS FOR NURSING: Identification of women at risk for
      fatigue and disturbed sleep may allow clinicians to intensify symptom management.

PMID- 29052654
TI  - Parents' Verbal and Nonverbal Caring Behaviors and Child Distress During Cancer
      Related Port Access Procedures: A Time-Window Sequential Analysis.
AB  - PURPOSE/OBJECTIVES: To study the relationship between parental verbal and
      nonverbal caring behaviors and child distress during cancer-related port access
      placement using correlational and time-window sequential analyses.?. DESIGN:
      Longitudinal, observational design.?. SETTING: Children's Hospital of Michigan
      and St. Jude Children's Research Hospital.?. SAMPLE: 43 child-parent dyads, each
      with two or three video recordings of the child undergoing cancer-related port
      placement.?. METHODS: Two trained raters coded parent interaction behaviors and
      child distress using the Parent Caring Response Scoring System and Karmanos Child
      Coping and Distress Scale, respectively. Mixed modeling with generalized
      estimating equations examined the associations between parent interaction
      behaviors and parent distress, child distress, and child cooperation reported by
      multiple raters. Time-window sequential analyses were performed to investigate
      the temporal relationships in parent-child interactions within a five-second
      window.?. MAIN RESEARCH VARIABLES: Parent caring behaviors, child distress, and
      child cooperation.?. FINDINGS: Parent caring interaction behaviors were
      significantly correlated with parent distress, child distress, and child
      cooperation during repeated cancer port accessing. Sequential analyses showed
      that children were significantly less likely to display behavioral and verbal
      distress following parent caring behaviors than at any other time. If a child is
      already distressed, parent verbal and nonverbal caring behaviors can
      significantly reduce child behavioral and verbal distress.?. CONCLUSIONS: Parent
      caring behaviors, particularly the rarely studied nonverbal behaviors (e.g., eye
      contact, distance close to touch, supporting/allowing), can reduce the child's
      distress during cancer port accessing procedures.?. IMPLICATIONS FOR NURSING:
      Studying parent-child interactions during painful cancer-related procedures can
      provide evidence to develop nursing interventions to support parents in caring
      for their child during painful procedures.

PMID- 29052655
TI  - Psychological Distress, Health Behaviors, and Benefit Finding in Survivors of
      Multiple Primary Cancers: Results From the 2010 Livestrong Survey.
AB  - PURPOSE/OBJECTIVES: To evaluate whether survivorship of multiple primary cancers
      (MPCs) is associated with psychological distress, positive health behaviors, and
      benefit finding.?. DESIGN: Secondary analysis of the 2010 Livestrong cross
      sectional survey.?. SETTING: Online survey.?. SAMPLE: 238 MPC survivors and 3,295
      single cancer survivors.?. METHODS: Chi-square and t tests for group comparisons
      were used. Multivariate linear regression, adjusted for covariates, was used to
      determine associations between variables.?. MAIN RESEARCH VARIABLES: MPC versus
      single cancer; psychological distress, health behavior (healthy lifestyle and
      positive healthcare utilization), and benefit-finding scores.?. FINDINGS:
      Survivors of MPCs (compared to single cancer survivors) were significantly older,
      less likely to have a spouse or partner, further out from original cancer
      diagnosis, and less likely to be employed full-time, and they differed by cancer
      diagnoses and survivorship stage. Having MPCs was associated with significantly
      higher psychological distress and healthcare utilization but not healthy
      lifestyle or benefit finding.?. CONCLUSIONS: Relative to those with single
      cancers, MPC survivors are at increased risk for psychological distress and are
      more likely to receive recommended cancer screenings. Additional research is
      needed to understand mechanisms surrounding psychological distress in MPC
      survivors.?. IMPLICATIONS FOR NURSING: Targeted distress screening in MPC
      survivors may allow for early identification and interventions to ameliorate
      distress and reduce negative downstream health effects.

PMID- 29052656
TI  - Initial Efficacy Testing of an Autobiographical Memory Intervention on Advance
      Care Planning for Patients With Terminal Cancer.
AB  - PURPOSE/OBJECTIVES: To test the efficacy of a novel intervention to facilitate
      advance care planning.?. DESIGN: Exploratory, quasiexperimental pilot study with
      two independent groups.?. SETTING: A large hospice located in the southwestern
      United States. ?. SAMPLE: A convenience sample of 50 participants with terminal
      cancer enrolled in hospice.?. METHODS: An autobiographical memory (ABM)
      intervention used the participants' experiences with cancer and end of life for
      the purpose of directing advance care planning.?. MAIN RESEARCH VARIABLES: Two
      domains of advance care planning, decision making and communication, were
      measured in relation to 11 variables. FINDINGS: The ABM intervention was
      nonthreatening, short in duration, and easily completed with participants as they
      recalled, without hesitation, specific personal memories of family and friends
      who had died and their advance care plans. The Mann-Whitney nonparametric test
      revealed that participants in the experimental group had a higher average rank
      than those in the control group for communicating the decision about antibiotics,
      as well as exhibited a trend toward significance for five other advance care
      planning variables.?. CONCLUSIONS: Findings showed that directive ABMs may be
      effective in influencing the decision making and communication of advance care
      planning for terminally ill patients with cancer.?. IMPLICATIONS FOR NURSING: The
      current level of understanding about using the ABM intervention suggests that
      nurses can initiate an advance care planning conversation using this approach.

PMID- 29052657
TI  - Uncertainty in Illness: Theory Review, Application, and Extension.
AB  - Mishel's uncertainty in illness theory provides a conceptual framework to explain
      how uncertainty is generated and how it affects psychological adjustment to the
      cancer experience. Since 1981, when it was created, researchers have used the
      theory to develop and test uncertainty management interventions in multiple
      populations of patients with cancer. This article reviews the theory's concepts
      and propositions, summarizes supporting evidence, and discusses extension of the
      theory, clinical implications, and future directions for research.

PMID- 29052658
TI  - Feasibility Study of an Online Intervention to Support Male Spouses of Women With
      Breast Cancer.
AB  - PURPOSE/OBJECTIVES: To evaluate the feasibility of a web-based psychosocial
      supportive intervention entitled Male Transition Toolkit (MaTT). ?. DESIGN:
      Randomized, controlled trial, mixed methods, concurrent feasibility design.?.
      SETTING: Edmonton, a large metropolitan city in western Canada.?. SAMPLE: 40
      dyads (women with breast cancer and their spouse).?. METHODS: Male spouse
      participants in the treatment group accessed MaTT for four weeks. Data on hope,
      quality of life, general self-efficacy, and caregiver guilt were collected at
      baseline and days 14, 28, and 56. Quality-of-life data were collected from the
      women with breast cancer at each time period. Qualitative data were collected
      from the usual care group in an open-ended interview and from the treatment group
      in an evaluation survey on days 14 and 28.?. MAIN RESEARCH VARIABLES:
      Feasibility, as measured by the MaTT questionnaire. ?. FINDINGS: Evaluation
      survey scores indicated that MaTT was feasible, acceptable, and easy to use. Male
      spouse quality-of-life scores were not significantly different between groups. As
      guilt scores decreased, male spouses' quality of life increased. ?. CONCLUSIONS:
      The findings provided useful information to strengthen MaTT and improve study
      design. Additional research is needed to determine its efficacy in improving male
      spouses' quality of life. ?. IMPLICATIONS FOR NURSING: MaTT is a feasible
      intervention. Future research should evaluate MaTT with larger samples as well as
      determine the amount of time participants used MaTT.

PMID- 29052659
TI  - The Predatory Journal Issue: Part II.
AB  - Every morning when I open my email, it is the same: 5-10 emails inviting me to
      submit my "valuable and esteemed" research to a journal that is new to me and
      just sounds off. Added to these invitations are a couple of requests to present
      at conferences in far-flung locations, often accompanied by photographs of
      "honored" presenters, mostly physicians; none of these publications or
      conferences are in my field, and they have generic titles and focus on general
      themes, such as "Global Nursing 2017." Every morning, I go through the same
      exercise: I flag them as junk and assume they will be blocked. But, the next
      morning, it is the same futile exercise. And I know many of you have the same
      daily ritual.?.

PMID- 29052660
TI  - Symptom Distress in Patients With Hepatocellular Carcinoma Toward the End of
      Life.
AB  - PURPOSE/OBJECTIVES: To describe the presence, frequency, severity, and distress
      of symptoms in outpatients with advanced hepatocellular carcinoma toward the end
      of life, and the variability in psychological and physical symptom distress
      between and within patients over time. ?. DESIGN: A prospective, longitudinal,
      descriptive design. ?. SETTING: Outpatient clinics at two healthcare
      institutions. ?. SAMPLE: 18 patients (15 men and 3 women) with hepatocellular
      carcinoma and a mean age of 63.3 years (range = 54-81 years).?. METHODS: Data
      were collected monthly for six months. Patients completed the Memorial Symptom
      Assessment Scale, which reports a total score, and three subscales that provide
      global distress, psychological distress, and physical distress scores.?. MAIN
      RESEARCH VARIABLES: Global, psychological, and physical distress.?. FINDINGS:
      Patients reported lack of energy and pain as the most frequent and distressing
      symptoms. Problems with sexual interest or activity was the fourth most present
      symptom after drowsiness. Global Distress Index mean scores had notable
      variability between and within patients over time. During data collection, six
      patients died. None were referred to palliative care.?. CONCLUSIONS: Gaining
      knowledge about symptom distress and prevalent symptoms experienced by patients
      with advanced hepatocellular carcinoma is critical for designing symptom
      management strategies that are comprehensive and tailored to patients to optimize
      their quality of life as they approach death.?. IMPLICATIONS FOR NURSING: Nurses
      play a vital role in advocating for, initiating, and providing comprehensive
      holistic care based on individual patient needs by facilitating discussions about
      apparent and less apparent distressing symptoms, including those related to
      sexuality.

PMID- 29052661
TI  - Adherence and Coping Strategies in Outpatients With Chronic Myeloid Leukemia
      Receiving Oral Tyrosine Kinase Inhibitors.
AB  - PURPOSE/OBJECTIVES: To assess adherence and coping strategies in outpatients with
      chronic myeloid leukemia (CML) on oral tyrosine kinase inhibitors (TKIs).?.
      DESIGN: Prospective, descriptive.?. SETTING: An interdisciplinary oncology
      outpatient clinic in Germany.?. SAMPLE: 35 outpatients with CML on oral TKIs.?.
      METHODS: Adherence and coping strategies were assessed with questionnaires.
      Clinical data were extracted from medical charts.?. MAIN RESEARCH VARIABLES:
      Adherence rates, main coping strategies, and frequency and contents of single
      coping strategies.?. FINDINGS: 18 patients showed adherence according to the
      applied screening instrument. Main coping strategies were spirituality and search
      for meaning. The two single items most frequently specified were adhering to
      medical instructions and trusting in the medical personnel involved.?.
      CONCLUSIONS: The low adherence rate of 51% most likely resulted from using the
      Basel Assessment of Adherence Scale as the questionnaire of choice. The relevance
      of spirituality and search for meaning as main coping strategies has not been
      shown previously in outpatients with CML. Most patients wish to obey medical
      instructions accurately and put trust in their oncologists; this introduces a
      resource that should gain relevance considering the increasing number of oral
      anticancer drugs.?. IMPLICATIONS FOR NURSING: Nurses are encouraged to routinely
      assess adherence and spiritual needs in outpatients with CML. Spirituality and
      search for meaning represent pivotal coping strategies in this group, which has
      an excellent prognosis. Oncology nurses may help provide tailored support,
      thereby ameliorating care for these patients.

PMID- 29052662
TI  - Evaluation of Online Learning Modules for Improving Physical Activity Counseling
      Skills, Practices, and Knowledge of Oncology Nurses.
AB  - PURPOSE/OBJECTIVES: To examine the effectiveness of online learning modules for
      improving physical activity counseling practices among oncology nurses. ?.
      DESIGN: Randomized, controlled trial.?. SETTING: Online.?. SAMPLE: 54 oncology
      nurses.?. METHODS: Oncology nurses were randomly assigned to the learning modules
      group or control group. The learning modules group completed six online learning
      modules and quizzes focused on physical activity for cancer survivors, general
      physical activity principles, and motivational interviewing.?. MAIN RESEARCH
      VARIABLES: Percentage of cancer survivors counseled, self-efficacy for physical
      activity counseling, knowledge of physical activity, and perceived barriers and
      benefits of physical activity counseling.?. FINDINGS: Analyses of covariance
      revealed no significant difference between the learning modules and control
      groups in the percentage of cancer survivors that oncology nurses counseled.
      Significant differences were found in self-efficacy for physical activity
      counseling and perceived barriers to physical activity counseling at
      postintervention. ?. CONCLUSIONS: The online learning intervention tested in this
      study improved some parameters of physical activity counseling but did not
      increase the percentage of cancer survivors that oncology nurses counseled.
      Additional pilot work is needed to refine the intervention.?. IMPLICATIONS FOR
      NURSING: This study suggests the potential utility of an evidence-based online
      learning strategy for oncology nurses that includes information on physical
      activity and its benefits in cancer survivorship. The findings offer a framework
      on how to implement physical activity counseling skills in oncology nursing
      practice.

PMID- 29052663
TI  - Self-Management Intervention for Adult Cancer Survivors After Treatment: A
      Systematic Review and Meta-Analysis.
AB  - PROBLEM IDENTIFICATION: This study aims to evaluate the effects of self
      management interventions (SMIs) for cancer survivors who completed primary
      treatment. ?. LITERATURE SEARCH: Using PubMed, EMBASE, CINAHL(r), PsycINFO(r),
      and Cochrane Central Register of Controlled Trails (CENTRAL), the authors
      conducted a systematic search of randomized, controlled trials published in
      English from database conception through June 2016. ?. DATA EVALUATION: The meta
      analysis was conducted with Cochrane Review Manager, version 5.3, and R program,
      version 3.3.1.?. SYNTHESIS: 12 studies were systematically reviewed for self
      management content, mode of delivery, session composition, and type of self
      management skills used. Then, a meta-analysis of nine randomized, controlled
      trials involving 2,804 participants was conducted comparing SMIs with usual care,
      attention control, and a waitlist group. Qualitative synthesis showed that (a)
      the major study population was comprised of breast cancer survivors; (b) SMIs
      focused on medical/behavioral and emotional management; (c) the most common mode
      of delivery was web-based; and (d) the most frequently evaluated outcomes were
      depression, self-efficacy, and health-related quality of life (HRQOL).
      Quantitative results demonstrated a significant medium effect on HRQOL and a
      large effect on fatigue of borderline significance. The effects on anxiety,
      depression, and self-efficacy were not statistically significant. ?. CONCLUSIONS:
      SMIs had a significant medium effect on HRQOL for cancer survivors post
      treatment, but the findings should be interpreted with caution because of
      substantial heterogeneity. In addition, the small number of studies limits
      conclusions. ?. IMPLICATIONS FOR NURSING: SMI as a nursing intervention for
      improving HRQOL of cancer survivors can be recommended, but more research should
      be undertaken to determine the most effective SMI format in terms of type, mode
      of delivery, and session composition.

PMID- 29052664
TI  - A Qualitative Study Exploring Models of Supportive Care in Men and Their
      Partners/Caregivers Affected by Metastatic Prostate Cancer.
AB  - PURPOSE/OBJECTIVES: To explore the experiences of patients with metastatic
      prostate cancer and their partners/caregivers, as well as an interprofessional
      team, with a nurse-led multimodality supportive care intervention. ?. RESEARCH
      APPROACH: Qualitative study. ?. SETTING: National Health Service (NHS), Tayside,
      Scotland.?. PARTICIPANTS: 19 patients, 7 partners/caregivers, and 7
      interprofessional members from four hospitals in NHS, Tayside, Scotland.?.
      METHODOLOGIC APPROACH: 33 semistructured interviews were conducted to explore
      patients' and partners/caregivers' experiences of supportive care, and a
      framework approach was used to analyze the data. ?. FINDINGS: Men and their
      partners/caregivers experienced a range of unmet physical, psychological, and
      informational supportive care needs. The participants in the intervention group
      reported overall high satisfaction with the use of holistic needs assessments and
      self-management plans, with a decrease in unmet needs compared to the standard of
      care over time. The prostate cancer specialist nurse was perceived as the hub of
      survivorship care. Members of the interprofessional team perceived benefit in the
      nurse-led multimodal supportive care intervention.?. INTERPRETATION: An emphasis
      needs to be placed on personalizing care, with supportive care interventions
      targeted to individual needs. ?. IMPLICATIONS FOR NURSING: Care can be improved
      by incorporating holistic needs assessment to target specialized interventions
      for optimized, individualized care plans. An intervention seminar encouraged self
      management and self-efficiency, leading to greater satisfaction for participants.

PMID- 29052665
TI  - Authorship Ethics in the Era of Team Science.
AB  - The dissemination of research findings in articles is essential. Held to the same
      ethical standards of the studies themselves, the level of contribution
      determining authorship and authorship order needs to be established a priori. In
      the current era of team science, with its focus on the acceleration of
      personalized care, many people are needed to answer comprehensive research
      questions. This article explores how a large number of authors can contribute
      meaningfully to team science articles.

PMID- 29052666
TI  - Patients' Perspectives of Engagement as a Safety Strategy.
AB  - PURPOSE/OBJECTIVES: To describe patient engagement as a safety strategy from the
      perspective of hospitalized surgical patients with cancer.?. RESEARCH APPROACH:
      Qualitative, descriptive approach using grounded theory.?. SETTING: Memorial
      Sloan Kettering Cancer Center in New York, New York.?. PARTICIPANTS: 13
      hospitalized surgical patients with cancer.?. METHODOLOGIC APPROACH: Grounded
      theory with maximum variation sampling.?. FINDINGS: Participants' perceptions
      regarding their engagement as a patient safety strategy were expressed through
      three overarching themes. CONCLUSIONS: Using direct messaging, such as "your
      safety" as opposed to "patient safety," and teaching patients specific behaviors
      to maintain their safety appeared to facilitate patient engagement and increase
      awareness of safety issues. Patients may be willing to accept some responsibility
      for ensuring their safety by engaging in behaviors that are intuitive or that
      they are clearly instructed to do; however, they described their involvement in
      their safety as a right, not an obligation.?. INTERPRETATION: Clear, inviting,
      multimodal communication appears to have the greatest potential to enhance
      patients' engagement in their safety. Nurses' ongoing assessment of patients'
      ability to engage is critical insofar as it provides the opportunity to encourage
      engagement without placing undue burden on them. By employing communication
      techniques that consider patients' perspectives, nurses can support patient
      engagement.

PMID- 29052667
TI  - Differences in Coping Among African American Women With Breast Cancer and Triple
      Negative Breast Cancer.
AB  - PURPOSE/OBJECTIVES: To determine differences in psychological distress, symptoms,
      coping capacity, and coping abilities among African American (AA) women with
      triple-negative breast cancer (TNBC) and non-TNBC and to explore differences in
      relationships among these variables.?. DESIGN: A prospective, descriptive,
      comparative, and correlational design.?. SETTING: Johns Hopkins Hospital in
      Baltimore, Maryland.?. SAMPLE: 30 AA women with breast cancer.?. METHODS:
      Patients completed questionnaires during chemotherapy. The Transactional Model of
      Stress and Coping was used to guide the research.?. MAIN RESEARCH VARIABLES:
      Psychological distress, symptoms, coping capacity, and coping ability.?.
      FINDINGS: Patients with non-TNBC reported more intense present total pain, nausea
      and vomiting, better emotional functioning, lower cognitive functioning, use of
      significantly more prayer and hope, and more coping self-statements. A lower
      coping capacity score was associated with psychological distress in the TNBC
      group at midpoint and in both groups at completion of chemotherapy treatment.
      Patients in both groups used a higher level of positive religious coping.?.
      CONCLUSIONS: AA women with TNBC and non-TNBC might benefit (reduced psychological
      distress and improved coping skills) from receiving a comprehensive psychological
      care program. The findings can be incorporated and tested in a comprehensive
      coping strategy program.?. IMPLICATIONS FOR NURSING: Nurses should work closely
      with AA women with breast cancer undergoing chemotherapy to help them identify
      and consciously use coping strategies associated with increased coping capacity.

PMID- 29052668
TI  - Mussel-mimetic hydrogels with defined cross-linkers achieved via controlled
      catechol dimerization exhibiting tough adhesion for wet biological tissues.
AB  - The engineering of catechol-based hydrogels to bind to wet biological tissues
      with high adhesion energy remains a challenge. Herein, fast quinone-nucleophile
      coupling and dynamic boronate ester bond were used to enhance the interfacial
      adhesion and bulk cohesion of our dual-crosslinked hydrogels, respectively, for
      fabricating mussel-mimetic tough adhesives.

PMID- 29052669
TI  - Facile synthesis of -C[double bond, length as m-dash]N- linked covalent organic
      frameworks under ambient conditions.
AB  - We reported herein a facile approach for the synthesis of -C[double bond, length
      as m-dash]N- linked covalent organic frameworks under ambient conditions. Three
      known (COF-42, COF-43, and COF-LZU1) and one new (Pr-COF-42) COF materials were
      successfully synthesized using this method. Furthermore, this simple synthetic
      approach makes the large-scale synthesis of -C[double bond, length as m-dash]N-
      linked COFs feasible.

PMID- 29052671
TI  - Quantum confinement of molecular deuterium clusters in carbon nanotubes: ab
      initio evidence for hexagonal close packing.
AB  - An ab initio study of quantum confinement of deuterium clusters in carbon
      nanotubes is presented. First, density functional theory (DFT)-based symmetry
      adapted perturbation theory is used to derive parameters for a pairwise potential
      model describing the adsorbate-nanotube interaction. Next, we analyze the quantum
      nuclear motion of N D2 molecules (N < 4) confined in carbon nanotubes using a
      highly accurate adsorbate-wave-function-based approach, and compare it with the
      motion of molecular hydrogen. We further apply an embedding approach and study
      zero-point energy effects on larger hexagonal and heptagonal structures of 7-8 D2
      molecules. Our results show a preference for crystalline hexagonal close packing
      hcp of D2 molecules inside carbon nanotubes even at the cost of a reduced
      volumetric density within the cylindrical confinement.

PMID- 29052672
TI  - TD-DFT calculations of one- and two-photon absorption in Coumarin C153 and
      Prodan: attuning theory to experiment.
AB  - We use TD-DFT to calculate the one-photon absorption (1PA) and two-photon
      absorption (2PA) properties of C153 and Prodan in toluene and DMSO, and benchmark
      different methods relative to accurate experimental data available from the
      literature on these particular systems. As the first step, we modify the range
      separated TD-DFT to provide the best prediction for the peak 1PA wavelength, and
      then apply the optimized functionals to achieve quantitative predictions of the
      corresponding two-photon absorption cross section, sigma2PA, with an accuracy ~10
      20% in C153 and ~20-30% in Prodan. To elucidate the origin of residual
      discrepancies between the theory and experimental observations, we invoked the
      two essential states model for sigma2PA, which allows us to verify not only the
      transition wavelength and the sigma2PA value, but also to quantitatively
      benchmark the calculation of key molecular parameters such as the transition
      dipole moment and the change of the permanent dipole moment. Such comprehensive
      cross-checking indicates that a larger discrepancy in Prodan is most likely
      caused by a noted failure of DFT to predict the relative intensity and relative
      ordering of closely lying excited states with different degrees of intramolecular
      charge transfer, which we further support by analyzing the predictions obtained
      by high-level coupled-cluster calculations in the gas phase. Our results
      highlight the utility of benchmarking the calculations not only relative to other
      theoretical methods, but also in comparison to the experimental measurements,
      wherever such data are available.

PMID- 29052670
TI  - Novel bis-cyclic guanidines as potent membrane-active antibacterial agents with
      therapeutic potential.
AB  - We designed a class of small dimeric cyclic guanidine derivatives which display
      potent antibacterial activity against both multidrug-resistant Gram-negative and
      Gram-positive bacteria. They could compromise bacterial membranes without
      developing resistance, inhibit biofilms formed by E. coli, and exhibit excellent
      in vivo activity in the MRSA-infected thigh burden mouse model.

PMID- 29052673
TI  - Ternary hybrid nanostructures of Au-CdS-ZnO grown via a solution-liquid-solid
      route using Au-ZnO catalysts.
AB  - Multi-component nanostructures of Au-CdS-ZnO with a novel morphology were
      synthesized by a non-conventional strategy where seeded growth is combined with
      solution-liquid-solid (SLS) growth. Each of these synthetic routes is used for
      growing a different domain of the final heterostructure, where ZnO rods are grown
      first on Au nanoparticles via heterogeneous nucleation while CdS is later grown
      between these two domains via SLS, using the Au tip of the preformed Au-ZnO as a
      catalyst. The in situ alloying of the Au tip with Cd enabled the metal tip to
      function as an SLS catalyst at a relatively mild reaction temperature which is
      lower than the melting point of pure Au.

PMID- 29052674
TI  - EGFR-targeting PLGA-PEG nanoparticles as a curcumin delivery system for breast
      cancer therapy.
AB  - Poor bioavailability and non-specificity of chemotherapeutic agents are major
      challenges in breast cancer treatment. Antibodies and small molecules that block
      cell signaling pathways have shown promise in the clinic, but their application
      is also limited by the high costs and treatment dosages required. Novel therapies
      that aim to rapidly and specifically target malignant cells with long-lasting
      impact in the tumor microenvironment may ultimately improve clinical outcome in
      cancer patients. Here, we demonstrate that epidermal growth factor receptor
      (EGFR)-targeting GE11 peptides conjugated with PEGylated polylactic-co-glycolic
      acid (PLGA) nanoparticles can be used to effectively deliver an anti-cancer
      agent, curcumin, into EGFR-expressing MCF-7 cells in vitro and in vivo. Treatment
      of breast cancer cells and tumor-bearing mice with these curcumin-loaded
      nanoparticles gave rise to reduced phosphoinositide 3-kinase signaling, decreased
      cancer cell viability, attenuated drug clearance from the circulation, and
      suppressed tumor burden compared with free curcumin or non-EGFR targeting
      nanoparticles. The targeted nanoscale drug delivery system we describe here may
      provide a new strategy for the design of targeted cancer therapy vectors. Our
      study provides evidence that the efficacy of pharmacologic anti-cancer agents can
      be enhanced through their delivery in the form of modified nanoparticles that
      effectively target specific malignant cell types.

PMID- 29052675
TI  - A novel upconversion luminescence derived photoelectrochemical immunoassay:
      ultrasensitive detection to alpha-fetoprotein.
AB  - Fabrication of near-infrared light-triggered photoelectrochemical (PEC) sensors
      based on the upconversion nanophosphors (UCNPs) is a novel approach, which
      exhibits the advantages of low background signal and non-damage to the biological
      substance as well as high sensitivity and improved electric detection in PEC
      sensors. Herein we demonstrate the preparation of novel and high-quality ZnO
      inverse opal photonic crystals (IOPCs)/Ag/NaYF4:Yb,Tm hybrid films by different
      advanced film techniques, including colloidal self-assembling, vapor phase
      deposition and pulsed laser deposition and its application to sensitive detection
      of alpha-fetoprotein (AFP). In the complex device, ZnO IOPCs and surface plasmon
      resonance (SPR) of silver had ability to largely enhance local excitation
      electromagnetic field of NaYF4:Yb,Tm, resulting in efficient near-infrared to
      visible/ultraviolet upconversion luminescence (UCL). The ultraviolet light
      emitted by NaYF4:Yb,Tm could b further reabsorbed by ZnO, generating PEC
      responses. Furthermore, because of the high specific surface area of ZnO IOPCs
      and the conductivity of Ag films, ZnO IOPCs/Ag/NaYF4:Yb,Tm hybrid films based
      near-infrared light-triggered PEC sensors showed ultrasensitive detection of AFP
      with a linear range from 0.05 ng mL-1 to 100 ng mL-1 and a low detection limit of
      ~0.04 ng mL-1 (40 pg mL-1). Such an advanced device also shows promise in
      detection of other cancer markers in clinical and biological analysis.

PMID- 29052676
TI  - Growth and nanomechanical characterization of nanoscale 3D architectures grown
      via focused electron beam induced deposition.
AB  - Nanomechanical measurements of platinum-carbon 3D nanoscale architectures grown
      via focused electron beam induced deposition (FEBID) were performed using a
      nanoindentation system in a scanning electron microscope (SEM) for simultaneous
      in situ imaging. Compression tests were used to estimate the modulus of the
      platinum-carbon deposits to be in the range of 8.6-10.5 GPa. Cantilever arm bend
      tests resulted in a modulus estimation of 15.6 GPa. Atomic layer deposition was
      used to conformally coat FEBID structures with a thin film of Al2O3, which
      strengthened the structures and increased the measured modulus. Cycled load
      displacement testing at various load rates of nano-truss structures was also
      performed, demonstrating a viscoelastic response in the FEBID material. Finally,
      load-displacement tests of a variety of 3-dimensional nanoarchitectures with and
      without Al2O3 coatings were measured.

PMID- 29052677
TI  - Silylene-assisted hydride transfer to CO2 and CS2 at a [P2Si]Ru pincer-type
      complex.
AB  - The synthesis and characterization of base-stabilized and base-free pincer-type
      bis(phosphine)/silylene [P2Si]Ru complexes are reported. The base-free complex
      readily reduces CO2 and CS2via silylene-assisted hydride transfer, affording
      structurally distinct products with silicon-to-ruthenium formate and
      dithioformate bridges.

PMID- 29052678
TI  - Oxidant-free synthesis of benzimidazoles from alcohols and aromatic diamines
      catalysed by new Ru(ii)-PNS(O) pincer complexes.
AB  - Benzimidazoles are chemically and pharmaceutically important, and an
      environmentally benign synthetic method based on acceptorless dehydrogenative
      condensation of primary alcohols and benzene-1,2-diamine is developed in this
      work. Three Ru(ii) hydride complexes [RuHCl(CO)(PNS(O))] (containing two isomers
      1a and 1b) and [RuHCl(CO)(PPh3)(SNCNHC)]PF6 (2) based on two new quinoline-based
      ligands 2-(diphenylphosphanylmethyl)-8-phenylsulfinylquinoline (PNS(O)) and 1
      mesityl-3-(8-phenylthioquinolyl-2-methyl)-2-imidazole carbene (SNCNHC) are
      prepared and fully characterized. These complexes catalyse the condensation of
      benzyl alcohol and benzene-1,2-diamine to 2-phenylbenzimidazole with the
      liberation of H2, and the catalytic activity follows the order: 1a ~ 1b > 2. When
      0.2 mol% of 1a and 2 mol% of NaBPh4 were used, various 2-functionalized
      benzimidazoles were obtained in good yields (70-85%) and high turnover numbers
      (TONs ~ 425). This homogeneous system does not need oxidants or stoichiometric
      strong bases (KOH or KOtBu, etc.) that are normally used in the reported
      homogeneous systems, and thus is a greener process.

PMID- 29052679
TI  - Oligonucleotide modifications enhance probe stability for single cell
      transcriptome in vivo analysis (TIVA).
AB  - Single cell transcriptomics provides a powerful discovery tool for identifying
      new cell types and functions as well as a means to probe molecular features of
      the etiology and treatment of human diseases, including cancer. However, such
      analyses are limited by the difficulty of isolating mRNA from single cells within
      biological samples. We recently introduced a photochemical method for isolating
      mRNA from single living cells, Transcriptome In Vivo Analysis (TIVA). The TIVA
      probe is a "caged" polyU : polyA oligonucleotide hairpin designed to enter live
      tissue, where site-specific activation with 405 nm laser reveals the polyU-biotin
      strand to bind mRNA in a target cell, enabling subsequent mRNA isolation and
      sequencing. The TIVA method is well suited for analysis of living cells in
      resected tissue, but has not yet been applied to living cells in whole organisms.
      Adapting TIVA to this more challenging environment requires a probe with higher
      thermal stability, more robust caging, and greater nuclease resistance. In this
      paper we present modifications to the original TIVA probe with multiple aspects
      of enhanced stability. These newer probes utilize an extended 22mer polyU capture
      strand with two 9mer polyA blocking strands ("22/9/9") for higher thermal
      stability pre-photolysis and improved mRNA capture affinity post-photolysis. The
      "22/9/9 GC" probe features a terminal GC pair to reduce pre-photolysis
      interactions with mRNA by more than half. The "PS-22/9/9" probe features a
      phosphorothioated backbone, which extends serum stability from <1 h to at least
      48 h, and also mediates uptake into cultured human fibroblasts.

PMID- 29052680
TI  - Progressive structural modification to a zinc-actuated photoinduced electron
      transfer (PeT) switch in the context of intracellular zinc imaging.
AB  - Photoinduced electron transfer (PeT)-type fluorescent molecular switches are
      often applied in ion-selective sensors. Zinc-targeting sensors that contain an
      anilino-based electron donor (aka, the PeT 'switch') have multiple advantages
      over those with an aliphatic amino switch. In addition to the lower pKa value of
      an aniline than that of a comparably substituted aliphatic amine, which reduces
      the interference of pH on the spectral properties of the attached fluorophore,
      the oxidation potentials of anilino groups are lower than those of aliphatic
      amino counterparts, which make them better electron donors in PeT. The
      effectiveness of anilino as a PeT switch is evaluated in a series of zinc
      sensitive sensors that contain different fluorophores, zinc-binding ligands, and
      alkyl linkers between ligand and fluorophore. The abilities of these compounds to
      distinguish high and low intracellular zinc concentrations in living cells are
      demonstrated.

PMID- 29052681
TI  - Thermodynamic signatures and cluster properties of self-assembly in systems with
      competing interactions.
AB  - Colloidal particles, amphiphiles and functionalized nanoparticles are examples of
      systems that frequently exhibit short-range attraction coupled with long-range
      repulsion. We vary the ratio of attraction and repulsion in a simple isotropic
      model with competing interactions, using molecular simulations, and observe
      significant differences in the properties of the self-assembled clusters that
      form. We report conditions that lead to the self-assembly of clusters of a
      preferred size, accompanied by a change in the slope of the pressure with respect
      to density, similar to micelles formed by amphiphilic molecules. We also report
      conditions where repulsion dominates, clusters of a preferred size form and the
      pressure vs. density slope is unaffected by self-assembly. We investigate cluster
      structure by calculating the size distributions, free colloid density, cluster
      shape and density profiles. The system dynamics are characterized by cluster life
      times. We do not find qualitative differences in structure or dynamics of the
      clusters, regardless the pressure behavior. Therefore, thermodynamic and
      structural quantities are required to classify the different clustering
      characteristics that are observable in systems with competing interactions. Our
      results have implications in terms of development of design principles for stable
      cluster self-assembly.

PMID- 29052682
TI  - Probing blood cell mechanics of hematologic processes at the single micron level.
AB  - Blood cells circulate in a dynamic fluidic environment, and during hematologic
      processes such as hemostasis, thrombosis, and inflammation, blood cells interact
      biophysically with a myriad of vascular matrices-blood clots and the
      subendothelial matrix. While it is known that adherent cells physiologically
      respond to the mechanical properties of their underlying matrices, how blood
      cells interact with their mechanical microenvironment of vascular matrices
      remains poorly understood. To that end, we developed microfluidic systems that
      achieve high fidelity, high resolution, single-micron PDMS features that mimic
      the physical geometries of vascular matrices. With these electron beam
      lithography (EBL)-based microsystems, the physical interactions of individual
      blood cells with the mechanical properties of the matrices can be directly
      visualized. We observe that the physical presence of the matrix, in and of
      itself, mediates hematologic processes of the three major blood cell types:
      platelets, erythrocytes, and leukocytes. First, we find that the physical
      presence of single micron micropillars creates a shear microgradient that is
      sufficient to cause rapid, localized platelet adhesion and aggregation that leads
      to complete microchannel occlusion; this response is enhanced with the presence
      of fibrinogen or collagen on the micropillar surface. Second, we begin to
      describe the heretofore unknown biophysical parameters for the formation of
      schistocytes, pathologic erythrocyte fragments associated with various thrombotic
      microangiopathies (poorly understood, yet life-threatening blood disorders
      associated with microvascular thrombosis). Finally, we observe that the physical
      interactions with a vascular matrix is sufficient to cause neutrophils to form
      procoagulant neutrophil extracellular trap (NET)-like structures. By combining
      electron beam lithography (EBL), photolithography, and soft lithography, we thus
      create microfluidic devices that provide novel insight into the response of blood
      cells to the mechanical microenvironment of vascular matrices and have promise as
      research-enabling and diagnostic platforms.

PMID- 29052683
TI  - Synthesis of indanes via carbene-catalyzed single-electron-transfer processes and
      cascade reactions.
AB  - A carbene-catalyzed cascade reaction is developed for the synthesis of multi
      substituted indane derivatives. The reaction involves two sequential Michael
      addition steps, of which the first step is enabled by an NHC-mediated radical
      process. This work demonstrates the synthetic potentials of NHC-mediated single
      electron-transfer processes for efficient reactions and rapid synthesis.

PMID- 29052685
TI  - Error in Table Data.

PMID- 29052684
TI  - Synthesis of an F-BODIPY [2]catenane using the chemistry of bis(dipyrrinato)metal
      complexes.
AB  - ML2 type complexes of an olefin terminated 5H-dipyrrin ligand can be subjected to
      twofold ring closing metathesis to give bis(dipyrrinato)copper(ii) and
      bis(dipyrrinato)zinc(ii) [2]catenates. Demetalation of the copper(ii) [2]catenate
      with KCN/N2H4.H2O gave the corresponding bis(dipyrrin) [2]catenand. The boron
      difluoride complex of this bis(dipyrrin) was obtained as the first fluorescent F
      BODIPY [2]catenane.

PMID- 29052686
TI  - Gadolinium Deposition in the Pediatric Brain.

PMID- 29052688
TI  - Risk of Tinnitus After Medial Temporal Lobe Surgery.

PMID- 29052689
TI  - An HIV Vaccine Is Essential for Ending the HIV/AIDS Pandemic.

PMID- 29052687
TI  - Association Between Early-Life Antibiotic Use and the Risk of Islet or Celiac
      Disease Autoimmunity.
AB  - Importance: Evidence is lacking regarding the consequences of antibiotic use in
      early life and the risk of certain autoimmune diseases. Objective: To test the
      association between early-life antibiotic use and islet or celiac disease (CD)
      autoimmunity in genetically at-risk children prospectively followed up for type 1
      diabetes (T1D) or CD. Design, Setting, and Participants: HLA-genotyped newborns
      from Finland, Germany, Sweden, and the United States were enrolled in the
      prospective birth cohort of The Environmental Determinants of Diabetes in the
      Young (TEDDY) study between November 20, 2004, and July 8, 2010. The dates of
      analysis were November 20, 2004, to August 31, 2014. Individuals from the general
      population and those having a first-degree relative with T1D were enrolled if
      they had 1 of 9 HLA genotypes associated with a risk for T1D. Exposures: Parental
      reports of the most common antibiotics (cephalosporins, penicillins, and
      macrolides) used between age 3 months and age 4 years were recorded
      prospectively. Main Outcomes and Measures: Islet autoimmunity and CD autoimmunity
      were defined as being positive for islet or tissue transglutaminase
      autoantibodies at 2 consecutive clinic visits at least 3 months apart. Hazard
      ratios and 95% CIs calculated from Cox proportional hazards regression models
      were used to assess the relationship between antibiotic use in early life before
      seroconversion and the development of autoimmunity. Results: Participants were
      8495 children (49.0% female) and 6558 children (48.7% female) enrolled in the
      TEDDY study who were tested for islet and tissue transglutaminase autoantibodies,
      respectively. Exposure to and frequency of use of any antibiotic assessed in this
      study in early life or before seroconversion did not influence the risk of
      developing islet autoimmunity or CD autoimmunity. Cumulative use of any
      antibiotic during the first 4 years of life was not associated with the
      appearance of any autoantibody (hazard ratio [HR], 0.98; 95% CI, 0.95-1.01),
      multiple islet autoantibodies (HR, 0.99; 95% CI, 0.95-1.03), or the
      transglutaminase autoantibody (HR, 1.00; 95% CI, 0.98-1.02). Conclusions and
      Relevance: The use of the most prescribed antibiotics during the first 4 years of
      life, regardless of geographic region, was not associated with the development of
      autoimmunity for T1D or CD. These results suggest that a risk of islet or tissue
      transglutaminase autoimmunity need not influence the recommendations for clinical
      use of antibiotics in young children at risk for T1D or CD.

PMID- 29052690
TI  - Compounded Bioidentical Hormone Therapy: Does the Regulatory Double Standard Harm
      Women?

PMID- 29052692
TI  - Overall Survival and Causes of Death in Neurodegeneration-An Overlooked and
      Underreported Theme-Reply.

PMID- 29052691
TI  - Discontinuing Inappropriate Medication Use in Nursing Home Residents: A Cluster
      Randomized Controlled Trial.
AB  - Background: Inappropriate prescribing is a well-known clinical problem in nursing
      home residents, but few interventions have focused on reducing inappropriate
      medication use. Objective: To examine successful discontinuation of inappropriate
      medication use and to improve prescribing in nursing home residents. Design:
      Pragmatic cluster randomized controlled trial, with clustering by elder care
      physicians and their wards. (ClinicalTrials.gov: NCT01876095). Setting: 59 Dutch
      nursing home wards for long-term care. Patients: Residents with a life expectancy
      greater than 4 weeks who consented to treatment with medication. Intervention:
      Multidisciplinary Multistep Medication Review (3MR) consisting of an assessment
      of the patient perspective, medical history, critical appraisal of medications, a
      meeting between the treating elder care physician and the pharmacist, and
      implementation of medication changes. Measurements: Successful discontinuation of
      use of at least 1 inappropriate drug (that is, without relapse or severe
      withdrawal symptoms) and clinical outcomes (neuropsychiatric symptoms, cognitive
      function, and quality of life) after 4 months of follow-up. Results: Nineteen
      elder care physicians (33 wards) performed the 3MR, and 16 elder care physicians
      (26 wards) followed standard procedures. A total of 426 nursing home residents
      (233 in the intervention group and 193 in the control group) were followed for an
      average of 144 days (SD, 21). In an analysis of all participants, use of at least
      1 inappropriate medication was successfully discontinued for 91 (39.1%) residents
      in the intervention group versus 57 (29.5%) in the control group (adjusted
      relative risk, 1.37 [95% CI, 1.02 to 1.75]). Clinical outcomes did not
      deteriorate between baseline and follow-up. Limitations: The 3MR was done only
      once. Some withdrawal symptoms or relapses may have been missed. Conclusion: The
      3MR is effective in discontinuing inappropriate medication use in frail nursing
      home residents without a decline in their well-being. Primary Funding Source:
      Netherlands Organisation for Health Research and Development.

PMID- 29052693
TI  - Medicare Formulary Coverage Restrictions for Prescription Opioids, 2006 to 2015.

PMID- 29052694
TI  - The Unrecognized Challenges of the Patient-Physician Relationship.

PMID- 29052695
TI  - Alternating Horner Syndrome With Vegetative Alterna and Spastic Quadraparesis
      After Bacterial Meningitis.

PMID- 29052696
TI  - Gadolinium Deposition in the Pediatric Brain-Reply.

PMID- 29052697
TI  - Association of Racial Differences With End-of-Life Care Quality in the United
      States.

PMID- 29052699
TI  - Overall Survival and Causes of Death in Neurodegeneration-An Overlooked and
      Underreported Theme.

PMID- 29052698
TI  - Novel Metrics for Improving Professional Fulfillment.

PMID- 29052700
TI  - Subclinical Primary Aldosteronism.

PMID- 29052701
TI  - Communication-and-Resolution Programs: The Jury Is Still Out.

PMID- 29052702
TI  - The Emotional Fallout From the Culture of Blame and Shame.

PMID- 29052703
TI  - Xp22.2 Chromosomal Duplication in Familial Intracranial Arachnoid Cyst.

PMID- 29052704
TI  - Patients' Experiences With Communication-and-Resolution Programs After Medical
      Injury.
AB  - Importance: Dissatisfaction with medical malpractice litigation has stimulated
      interest by health care organizations in developing alternatives to meet
      patients' needs after medical injury. In communication-and-resolution programs
      (CRPs), hospitals and liability insurers communicate with patients about adverse
      events, use investigation findings to improve patient safety, and offer
      compensation when substandard care caused harm. Despite increasing interest in
      this approach, little is known about patients' and family members' experiences
      with CRPs. Objective: To explore the experiences of patients and family members
      with medical injuries and CRPs to understand different aspects of institutional
      responses to injury that promoted and impeded reconciliation. Design, Setting,
      and Participants: From January 6 through June 30, 2016, semistructured interviews
      were conducted with patients (n = 27), family members (n = 3), and staff (n = 10)
      at 3 US hospitals that operate CRPs. Patients and families were eligible for
      participation if they experienced a CRP, spoke English, and could no longer file
      a malpractice claim because they had accepted a settlement or the statute of
      limitations had expired. The CRP administrators identified hospital and insurer
      staff who had been involved in a CRP event and had a close relationship with the
      injured patient and/or family. They identified patients and families by applying
      the inclusion criteria to their CRP databases. Of 66 possible participants, 40
      interviews (61%) were completed, including 30 of 50 invited patients and families
      (60%) and 10 of 16 invited staff (63%). Main Outcomes and Measures: Patients'
      reported satisfaction with disclosure and reconciliation efforts made by
      hospitals. Results: A total of 40 participants completed interviews (15 men and
      25 women; mean [range] age, 46 [18-67] years). Among the 30 patients and family
      members interviewed, 27 patients experienced injuries attributed to error and
      received compensation. The CRP experience was positive overall for 18 of the 30
      patients and family members, and 18 patients continued to receive care at the
      hospital. Satisfaction was highest when communications were empathetic and
      nonadversarial, including compensation negotiations. Patients and families
      expressed a strong need to be heard and expected the attending physician to
      listen without interrupting during conversations about the event. Thirty-five of
      the 40 respondents believed that including plaintiffs' attorneys in these
      discussions was helpful. Sixteen of the 30 patients and family members deemed
      their compensation to be adequate but 17 reported that the offer was not
      sufficiently proactive. Patients and families strongly desired to know what the
      hospital did to prevent recurrences of the event, but 24 of 30 reported receiving
      no information about safety improvement efforts. Conclusions and Relevance: As
      hospitals strive to provide more patient-centered care, opportunities exist to
      improve institutional responses to injuries and promote reconciliation.

PMID- 29052705
TI  - Pitfalls of Single-Electrocardiogram Lead Monitoring: A Lead of Deceit.

PMID- 29052706
TI  - Association of an Electroencephalography-Based Risk Score With Seizure
      Probability in Hospitalized Patients.
AB  - Importance: Continuous electroencephalography (EEG) use in critically ill
      patients is expanding. There is no validated method to combine risk factors and
      guide clinicians in assessing seizure risk. Objective: To use seizure risk
      factors from EEG and clinical history to create a simple scoring system
      associated with the probability of seizures in patients with acute illness.
      Design, Setting, and Participants: We used a prospective multicenter (Emory
      University Hospital, Brigham and Women's Hospital, and Yale University Hospital)
      database containing clinical and electrographic variables on 5427 continuous EEG
      sessions from eligible patients if they had continuous EEG for clinical
      indications, excluding epilepsy monitoring unit admissions. We created a scoring
      system model to estimate seizure risk in acutely ill patients undergoing
      continuous EEG. The model was built using a new machine learning method
      (RiskSLIM) that is designed to produce accurate, risk-calibrated scoring systems
      with a limited number of variables and small integer weights. We validated the
      accuracy and risk calibration of our model using cross-validation and compared
      its performance with models built with state-of-the-art logistic regression
      methods. The database was developed by the Critical Care EEG Research Consortium
      and used data collected over 3 years. The EEG variables were interpreted using
      standardized terminology by certified reviewers. Exposures: All patients had more
      than 6 hours of uninterrupted EEG recordings. Main Outcomes and Measures: The
      main outcome was the average risk calibration error. Results: There were 5427
      continuous EEGs performed on 4772 participants (2868 men, 49.9%; median age, 61
      years) performed at 3 institutions, without further demographic stratification.
      Our final model, 2HELPS2B, had an area under the curve of 0.819 and average
      calibration error of 2.7% (95% CI, 2.0%-3.6%). It included 6 variables with the
      following point assignments: (1) brief (ictal) rhythmic discharges (B[I]RDs) (2
      points); (2) presence of lateralized periodic discharges, lateralized rhythmic
      delta activity, or bilateral independent periodic discharges (1 point); (3) prior
      seizure (1 point); (4) sporadic epileptiform discharges (1 point); (5) frequency
      greater than 2.0 Hz for any periodic or rhythmic pattern (1 point); and (6)
      presence of "plus" features (superimposed, rhythmic, sharp, or fast activity) (1
      point). The probable seizure risk of each score was 5% for a score of 0, 12% for
      a score of 1, 27% for a score of 2, 50% for a score of 3, 73% for a score of 4,
      88% for a score of 5, and greater than 95% for a score of 6 or 7. Conclusions and
      Relevance: The 2HELPS2B model is a quick accurate tool to aid clinical judgment
      of the risk of seizures in critically ill patients.

PMID- 29052708
TI  - Typographical Errors in the Table.

PMID- 29052710
TI  - Saying Goodbye.

PMID- 29052709
TI  - Association of Prognostic Factors and Immunosuppressive Treatment With Long-term
      Outcomes in Neurosarcoidosis.
AB  - Importance: Prognostic factors are lacking in neurosarcoidosis (NS), and the
      association of immunosuppressive treatments with outcomes are unclear.
      Objectives: To identify prognostic factors of and analyze the association of
      immunosuppressive treatment with relapse of NS. Design, Setting, and
      Participants: In this retrospective study, a cohort of 234 patients fulfilled the
      diagnostic criteria for NS in a tertiary referral center in Paris, France, from
      January 1, 1990, through December 31, 2015. The median follow-up was 8 years
      (range, 2 months to 23 years). Main Outcomes and Measures: All neurologic and
      extraneurologic data and treatments were analyzed. Functional outcomes measured
      by the absolute value and the variation from baseline of the Expanded Disability
      Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and
      relapse-free survival (RFS) were assessed. Analyses were stratified by the period
      of NS diagnosis (1990-1999 vs 2000-2015). Results: The 234 patients undergoing
      assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42
      years (interquartile range, 32-53 years). The probable 10-year survival rate was
      89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI,
      1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI,
      2.31-19.7; P < .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI,
      1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS
      rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for
      neurologic relapses. Encephalic involvement was associated with shorter
      neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P < .001). A lower risk for relapse
      was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001),
      methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR,
      0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60
      months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR]
      per point, 1.92; 95% CI, 1.55-2.37; P < .001), tobacco use (OR, 3.64; 95% CI,
      1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI, 1.11-8.38; P = .03),
      and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04
      8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months.
      Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral
      nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated
      with worsening of the EDSS score at 60 months. Conclusions and Relevance: This
      study identifies putative factors affecting morbidity and mortality in patients
      with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide,
      methotrexate, and infliximab) in these patients may be associated with lower
      relapse rates.

PMID- 29052711
TI  - Evaluation of a Trainee-Led Project to Reduce Inappropriate Proton Pump Inhibitor
      Infusion in Patients With Upper Gastrointestinal Bleeding: Skip the Drips.

PMID- 29052707
TI  - The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A
      Cohort Study.
AB  - Background: Primary aldosteronism is recognized as a severe form of renin
      independent aldosteronism that results in excessive mineralocorticoid receptor
      (MR) activation. Objective: To investigate whether a spectrum of subclinical
      renin-independent aldosteronism that increases risk for hypertension exists among
      normotensive persons. Design: Cohort study. Setting: National community-based
      study. Participants: 850 untreated normotensive participants in MESA (Multi
      Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and
      plasma renin activity (PRA). Measurements: Longitudinal analyses investigated
      whether aldosterone concentrations, in the context of physiologic PRA phenotypes
      (suppressed, <=0.50 ug/L per hour; indeterminate, 0.51 to 0.99 ug/L per hour;
      unsuppressed, >=1.0 ug/L per hour), were associated with incident hypertension
      (defined as systolic blood pressure >=140 mm Hg, diastolic blood pressure >=90 mm
      Hg, or initiation of antihypertensive medications). Cross-sectional analyses
      investigated associations between aldosterone and MR activity, assessed via serum
      potassium and urinary fractional excretion of potassium. Results: A suppressed
      renin phenotype was associated with a higher rate of incident hypertension than
      other PRA phenotypes (incidence rates per 1000 person-years of follow-up:
      suppressed renin phenotype, 85.4 events [95% CI, 73.4 to 99.3 events];
      indeterminate renin phenotype, 53.3 events [CI, 42.8 to 66.4 events];
      unsuppressed renin phenotype, 54.5 events [CI, 41.8 to 71.0 events]). With renin
      suppression, higher aldosterone concentrations were independently associated with
      an increased risk for incident hypertension, whereas no association between
      aldosterone and hypertension was seen when renin was not suppressed. Higher
      aldosterone concentrations were associated with lower serum potassium and higher
      urinary excretion of potassium, but only when renin was suppressed. Limitation:
      Sodium and potassium were measured several years before renin and aldosterone.
      Conclusion: Suppression of renin and higher aldosterone concentrations in the
      context of this renin suppression are associated with an increased risk for
      hypertension and possibly also with increased MR activity. These findings suggest
      a clinically relevant spectrum of subclinical primary aldosteronism (renin
      independent aldosteronism) in normotension. Primary Funding Source: National
      Institutes of Health.

PMID- 29052712
TI  - Changing Physician Approaches to Marijuana Use in a New Era of Legalization.

PMID- 29052713
TI  - Knowledge for Precision Medicine: Mechanistic Reasoning and Methodological
      Pluralism.

PMID- 29052714
TI  - Firearm-Related Injury and Death: A U.S. Health Care Crisis in Need of Health
      Care Professionals.

PMID- 29052715
TI  - Meaningful Deprescribing in the Nursing Home.

PMID- 29052716
TI  - The Las Vegas Shootings-Underscoring Key Features of the Firearm Epidemic.

PMID- 29052717
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052718
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052719
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052720
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052721
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052722
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052723
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052724
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052725
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052726
TI  - Error in Abstract.

PMID- 29052729
TI  - Consonant Age-of-Acquisition Effects in Nonword Repetition Are Not Articulatory
      in Nature.
AB  - Purpose: Most research examining long-term-memory effects on nonword repetition
      (NWR) has focused on lexical-level variables. Phoneme-level variables have
      received little attention, although there are reasons to expect significant
      sublexical effects in NWR. To further understand the underlying processes of NWR,
      this study examined effects of sublexical long-term phonological knowledge by
      testing whether performance differs when the stimuli comprise consonants acquired
      later versus earlier in speech development. Method: Thirty (Experiment 1) and 20
      (Experiment 2) college students completed tasks that investigated whether an
      experimental phoneme-level variable (consonant age of acquisition) similarly
      affects NWR and lexical-access tasks designed to vary in articulatory, auditory
      perceptual, and phonological short-term-memory demands. The lexical-access tasks
      were performed in silence or with concurrent articulation to explore whether
      consonant age-of-acquisition effects arise before or after articulatory planning.
      Results: NWR accuracy decreased on items comprising later- versus earlier
      acquired phonemes. Similar consonant age-of-acquisition effects were observed in
      accuracy measures of nonword reading and lexical decision performed in silence or
      with concurrent articulation. Conclusion: Results indicate that NWR performance
      is sensitive to phoneme-level phonological knowledge in long-term memory. NWR,
      accordingly, should not be regarded as a diagnostic tool for pure impairment of
      phonological short-term memory. Supplemental Materials:
      https://doi.org/10.23641/asha.5435137.

PMID- 29052731
TI  - Demystifying Neurosarcoidosis and Informing Prognosis.

PMID- 29052730
TI  - The reward of seeing: Different types of visual reward and their ability to
      modify oculomotor learning.
AB  - Saccadic adaptation is an oculomotor learning process that maintains the accuracy
      of eye movements to ensure effective perception of the environment. Although
      saccadic adaptation is commonly considered an automatic and low-level motor
      calibration in the cerebellum, we recently found that strength of adaptation is
      influenced by the visual content of the target: pictures of humans produced
      stronger adaptation than noise stimuli. This suggests that meaningful images may
      be considered rewarding or valuable in oculomotor learning. Here we report three
      experiments that establish the boundaries of this effect. In the first, we tested
      whether stimuli that were associated with high and low value following long term
      self-administered reinforcement learning produce stronger adaptation. Twenty
      eight expert gamers participated in two sessions of adaptation to game-related
      high- and low-reward stimuli, but revealed no difference in saccadic adaptation
      (Bayes Factor01 = 5.49). In the second experiment, we tested whether cognitive
      (literate) meaning could induce stronger adaptation by comparing targets
      consisting of words and nonwords. The results of twenty subjects revealed no
      difference in adaptation strength (Bayes Factor01 = 3.21). The third experiment
      compared images of human figures to noise patterns for reactive saccades. Twenty
      two subjects adapted significantly more toward images of human figures in
      comparison to noise (p < 0.001). We conclude that only primary (human vs. noise),
      but not secondary, reinforcement affects saccadic adaptation (words vs. nonwords,
      high- vs. low-value video game images).

PMID- 29052732
TI  - A Novel Clinical Score to Assess Seizure Risk.

PMID- 29052733
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052734
TI  - Diagnostic Performance of Magnetic Resonance Enterography for Detection of Active
      Inflammation in Children and Adolescents With Inflammatory Bowel Disease: A
      Systematic Review and Diagnostic Meta-analysis.
AB  - Importance: Magnetic resonance (MR) enterography has the advantage over other
      techniques of being noninvasive, lacking ionizing radiation, and demonstrating
      excellent soft-tissue contrast to evaluate pediatric patients with inflammatory
      bowel disease (IBD). Objective: To evaluate the diagnostic performance of MR
      enterography for detection of active inflammation in children and adolescents
      with known or suspected IBD. Data Sources: A search of MEDLINE and EMBASE up to
      January 2, 2017, was performed to identify studies. Search terms included child,
      pediatric, adolescent, Crohn disease, inflammatory bowel disease, and magnetic
      resonance enterography. The search was limited to English-language publications.
      Study Selection: Studies evaluating the diagnostic performance of MR enterography
      for detection of active inflammation in pediatric patients with known or
      suspected IBD were selected. Two reviewers independently assessed the eligibility
      of the selected articles. Data Extraction and Synthesis: The study was performed
      and reported in accordance with the PRISMA guidelines. Pooled summary estimates
      of sensitivity and specificity were calculated using hierarchical logistic
      regression modeling. Main Outcomes and Measures: The diagnostic performance of MR
      enterography for detection of active inflammation in pediatric patients with
      known or suspected IBD was the primary outcome. Subgroup analyses and meta
      regression were performed. Results: Eighteen original articles involving a total
      of 687 patients were included. The summary sensitivity was 83% (95% CI, 75%-89%),
      the summary specificity was 93% (95% CI, 90%-95%), and the area under the
      hierarchical summary receiver operating characteristic curve was 0.95 (95% CI,
      0.93-0.97). The Higgins I2 statistics demonstrated substantial heterogeneity in
      terms of sensitivity (I2 = 84.1%) and specificity (I2 = 68.8%). Based on per
      patient analysis, the summary sensitivity was 86% (95% CI, 78%-91%) and
      specificity was 91% (95% CI, 82%-96%). In meta-regression, among the various
      potential covariates, scanner manufacturer was associated with study
      heterogeneity. Conclusions and Relevance: Magnetic resonance enterography, which
      is a noninvasive, radiation-free modality, demonstrates high diagnostic
      performance in the diagnosis of active inflammation in pediatric patients with
      IBD, especially at the per-patient level.

PMID- 29052735
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052736
TI  - Death by Gun Violence-A Public Health Crisis.

PMID- 29052737
TI  - Can this patient be safely weaned from RRT?

PMID- 29052738
TI  - [Obituary for Prof. Dr. Reiner Benecke (1949-2017)].

PMID- 29052739
TI  - Spatial Distribution of Metals and Associated Risks in Surface Sediments Along a
      Typical Urban River Gradient in the Beijing Region.
AB  - Surface sediments from Beiyun River located in the rapidly urbanized Beijing
      metropolis were collected and analyzed for heavy metals (As, Cd, Cr, Cu, Mn, Ni,
      Pb, and Zn) to investigate their spatial distribution pattern, ecotoxicology and
      source identification. Results indicated the average heavy metal concentrations
      of Cd, Cr, Cu, Pb, and Zn were approximately 4, 2, 3, 2, and 4 times higher than
      their background values. Spatially, we found the concentrations of heavy metals
      made significant change in four sections along urbanized river gradients. The
      contents in midstream of urban region and farmland region (section 2 and section
      3) were greater than those in upstream (section 1) and downstream (section 4).
      However, one-way analysis of variance for spatial analysis suggested there were
      no significant differences between mainstream and tributaries. The geo
      accumulation index (I geo) used to assess the sediment quality exhibited there
      was a decreasing order for the average I geo of measured heavy metals: Zn (0.82)
      > Cd (0.53) > Cu (0.50) > Cr (- 0.08) > Pb (- 0.45) > Ni (- 0.96) > Mn (- 0.97) >
      As (- 1.01), whereas they had different "high-low" orders at different sampling
      transects. Ecological risk index values showed that section 2 and section 3
      revealed a high and moderate ecological risk, respectively. Furthermore,
      principal component analysis indicated the first principle component explained
      64.73% of total variance with the main pollutants of As, Cr, Ni, Zn, and Cu which
      were probably controlled by the mixed sources covering natural factors and
      anthropogenic input.

PMID- 29052740
TI  - Short-Term Effects of the Anti-sea Lice Therapeutant Emamectin Benzoate on Clam
      Worms (Nereis virens).
AB  - The polychaete Nereis virens occurs commonly in marine sediments, is widely
      distributed, and is a popular bait species, as well as a potential replacement
      for wild-caught fish in commercial fish feed preparations. It is being considered
      as a potential co-extractive species for culture in integrated multi-trophic
      aquaculture operations. However, it is not known whether pesticides or drugs used
      to treat sea lice on farmed salmon, such as emamectin benzoate (EB), would
      adversely affect cultured or wild worms, because these compounds may persist in
      the environment. To determine the potential effects of EB to N. virens, bioassays
      were performed wherein worms were exposed in sand for 30 days to a concentration
      of 400 ug/kg dw (nominal). While no treatment-related mortality occurred,
      significant decreases in worm mass and marked behavioral changes (lack of
      burrowing) were observed in EB-treated sand compared with controls. These lab
      based observations suggest a potential hazard to worms at sites where EB
      treatments have occurred.

PMID- 29052741
TI  - [Regional differences of ADHD diagnosis rates in health insurance data from 2005
      to 2015 : Methodological considerations and results].
AB  - BACKGROUND AND OBJECTIVES: Attention deficit hyperactivity disorders (ADHD) are
      among the most common mental disorders in children and adolescents. For a number
      of years there has been evidence of regional differences in Germany. This article
      provides current results on the frequency of diagnosis and treatment and also
      discusses methodological aspects. MATERIALS AND METHODS: The analysis is based on
      routine data of a statutory health insurance company including annual diagnoses
      and drug prescriptions from 2005 to 2015 of at least 1.34 million children and
      adolescents between 0 and 19 years of age. Small-area results of ADHD diagnosis
      rates and methylphenidate prescriptions are presented with a standardized
      differentiation according to 413 districts pursuant to territorial status from
      the end of 2008. RESULTS: From 2005 to 2014, ADHD diagnoses were documented for
      an increasing proportion of 0 to 19-year-olds in Germany. In 2015 the proportion
      was 4.2%; boys aged 10 were affected most frequently with a proportion of 11.1%.
      Regional diagnosis rates vary considerably. Two counties showed diagnosis and
      prescription rates that were more than twice as high as regionally expected for
      all years in question; other districts showed rates that were continually lower
      than expected by at least a third. DISCUSSION: Analyses on the level of
      administratively defined districts have some advantages but alternative regional
      structuring would be desirable due to very heterogeneous population figures.
      Regarding ADHD diagnoses and documented methylphenidate prescriptions on an
      outpatient basis, significant regional differences in Germany were detected, for
      which plausible medical justifications do not yet exist. Specialist discussions
      seem urgently needed.

PMID- 29052742
TI  - [Triple arthrodesis for correction of cavovarus deformity].
AB  - OBJECTIVE: The aim is to correct the underlying cavovarus deformity and to
      achieve a pain-free and stable hindfoot. INDICATIONS: Rigid neurologic,
      posttraumatic, congenital, and idiopathic cavovarus deformities.
      CONTRAINDICATIONS: General surgical or anesthesiological risks, infections,
      critical soft tissue conditions, neurovascular impairment of the lower extremity,
      noncompliance, patients with severely reduced bone quality, insulin-dependent
      diabetes mellitus, smoking. SURGICAL TECHNIQUE: The talonavicular and subtalar
      joints are exposed using a single medial approach. Joint cartilage is carefully
      debrided. Hindfoot reposition with complete correction of cavovarus deformity in
      all three planes. Joints are stabilized using cannulated screws, followed by
      wound closure. POSTOPERATIVE MANAGEMENT: A soft wound dressing is used.
      Thromboprophylaxis is recommended. Patient mobilization starts on postoperative
      day 1 using a stabilizing walking boot or cast for 6 weeks with 15 kg partial
      weight bearing. Clinical and radiographic follow-up 6 weeks postoperatively to
      assess osseous consolidation at the arthrodesis site. Following clinical and
      radiographic follow-up at 6 weeks, full weight bearing is gradually initiated.
      RESULTS: Between January 2012 and July 2014, triple arthrodesis was performed in
      11 patients with a mean age of 62 +/- 14 years due to cavovarus deformity. The
      mean follow-up was 34 +/- 8 months (range 24-48 months). In all patients, the
      cavovarus deformity was substantially corrected. Significant pain relief from 7.1
      +/- 2.2 (range 5-10) to 1.8 +/- 1.5 (range 0-4) on the visual analogue scale was
      observed.

PMID- 29052743
TI  - Letter to the Editor Regarding "Growth of Untreated Unruptured Small-sized
      Aneurysms (<7 mm): Incidence and Related Factors".

PMID- 29052744
TI  - Tibiofemoral joint congruence is lower in females with ACL injuries than males
      with ACL injuries.
AB  - PURPOSE: Previous research has demonstrated that women have a higher risk of
      anterior cruciate ligament (ACL) injury than men. Tibiofemoral articular geometry
      may play a role in the occurrence of ACL tears. The purpose of this study was to
      analyze the gender-specific geometric characteristics differences in tibiofemoral
      morphology in ACL-deficient patients. METHODS: Medial tibial slope (MTS), lateral
      tibial slope (LTS), medial tibial plateau concavity, medial and lateral femoral
      condyle convexity, and lateral plateau convexity were analyzed in 276 patients
      with complete ACL injuries (138 females and 138 males). Two blinded observers
      measured the anatomical parameters of tibiofemoral geometry with use of
      multiplanar CT scans. Intra- and inter-rater reliabilities were assessed and
      comparisons between anatomic measures were made between male and female patients.
      RESULTS: The average ICC for all measurements was 0.90 (range 0.83-0.97)
      indicating good reliability. Male ACL injured patients demonstrated significantly
      greater LTS (10.5 degrees  +/- 2.8) than female patients (9.6 degrees  +/- 3.5
      degrees ; p < 0.05). No gender difference in MTS was found (n.s.). Medial and
      lateral femoral condyle convexity and medial tibial plateau concavity were
      greater in males than females (all p < 0.05). Lateral tibial plateau convexity in
      females was higher than in males (p < 0.001). The medial and lateral compartments
      were found to be more incongruent in females than males (p < 0.01 and p < 0.001,
      respectively). CONCLUSIONS: Female patients were noted to have more incongruent
      medial and lateral compartments than male patients. These gender-specific
      differences in joint morphology may contribute to graft tear risk and outcomes of
      ACL reconstruction; however, comparative clinical studies are needed to confirm
      this possibility. LEVEL OF EVIDENCE: 3.

PMID- 29052746
TI  - [Rare cause of painful swelling in the right groin].

PMID- 29052745
TI  - Role of Fat and Bone Biomarkers in the Relationship Between Ethnicity and Bone
      Mineral Density in Older Men.
AB  - Osteoporosis is an important health issue for older adults, and has been
      relatively understudied in older men. This study aimed to examine ethnic
      differences in bone mineral density (BMD), and elucidate the role of bone
      turnover markers (BTMs), fat and fat biomarkers on these ethnic differences. BMD
      at the lumbar spine and femoral neck, marrow fat at femoral neck, visceral
      adipose tissue (VAT) and subcutaneous adipose tissue, bone and fat biomarkers
      were evaluated in 120 healthy men aged >= 60 years. Indians had higher BMD values
      compared to Chinese at the lumbar spine (beta = 20.336, SE = 4.749, p < 0.001)
      and the femoral neck (e beta  = 1.105, SE = 0.032, p < 0.001), after adjusting
      for BTMs, fat composition and lifestyle choices. Marrow fat, VAT and adiponectin
      were independent predictors of BMD. However, these factors did not explain the
      lower BMD observed in older Chinese men. Our findings suggest that older Chinese
      men are at significant risk of osteoporotic fractures due to lower BMD. Fat
      appears to be a key factor associated with lower BMD, and warrants further
      longitudinal studies to elucidate the complex interactions between adipose tissue
      and bone strength.

PMID- 29052747
TI  - Angiosomal radiopathologic analysis of transarterial radioembolization for the
      treatment of hepatocellular carcinoma.
AB  - PURPOSE: To assess the radiopathologic correlation following Yttrium-90
      transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC) using
      variable radiodosimetry to identify imaging surrogates of histologic response.
      METHODS: Twelve patients with HCC underwent ablative (>= 190 Gy) and/or non
      ablative (< 190 Gy) TARE delivered in a segmental, lobar, or combined fashion as
      a surgical neoadjuvant or bridge to transplantation. Both targeted tumor and
      treatment angiosome were analyzed before and after TARE utilizing hepatocyte
      specific contrast-enhanced MRI or contrast-enhanced CT. Responses were graded
      using EASL and mRECIST criteria. Histologic findings including percent tumor
      necrosis and adjacent hepatic substrate effects were correlated with imaging
      features. RESULTS: Complete pathologic necrosis (CPN) was observed in 7/12 tumors
      post-TARE. Ablative and non-ablative dosing resulted in CPN in 5/6 and 2/6
      tumors, respectively. Hyperintensity on T2-weighted imaging, the absence of
      hepatocyte-specific gadolinium contrast uptake, and plateau or persistent
      enhancement kinetics in the angiosome correlated with CPN and performed similarly
      to EASL and mRECIST criteria in predicting CPN. CONCLUSIONS: The absence of
      hepatocyte-specific contrast uptake, increased signal on T2-weighted sequences,
      and plateau or persistent enhancement in the angiosome may represent MRI
      surrogates of CPN following TARE of HCC. These findings correlated with EASL and
      mRECIST response criteria. Further investigation is needed to determine the role
      of these findings as possible adjuncts to conventional imaging criteria.

PMID- 29052748
TI  - [Heart valve disesases : How sufficient is the knowledge of the German
      population?]
AB  - To evaluate the awareness and knowledge of the German population regarding
      diseases in general, a survey of 1446 people aged 60 years or older was conducted
      in 14 German towns. The focus was on heart valve diseases with special emphasis
      on aortic valve stenosis (AS). While cancer was the disease that respondents were
      most concerned about (25.2%), only 3.3% were concerned about heart valve
      diseases. In this respect, the knowledge was broadly limited: only 7.4% of
      participants claimed to have some familiarity with heart valve diseases and only
      12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the
      participants could correctly name the number of human heart valves, 71.6% knew at
      least one therapy option for AS and 30.6% were familiar with transcatheter aortic
      valve implantation (TAVI). After providing a brief clarification of the
      prevalence, symptoms and course of AS, 45.6% of respondents were more concerned
      about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7%
      even recognized the typical symptoms in themselves. Most of the participants
      would like to seek more information preferably in discussion with a specialist
      physician (77.2%), with their general practitioner (43.2%) or using the internet
      (29.7%). Despite its high prevalence, high morbidity and mortality, the vast
      majority of the German population were neither concerned nor fully aware of
      treatment options for AS. There is a strong case for public awareness campaigns
      that provide better knowledge of AS, and support check-ups that enable timely
      treatment and the avoidance of unnecessary hospitalization and death.

PMID- 29052749
TI  - [Body experience and self-esteem after minimally invasive skin rejuvenation :
      Study of female patients using botulinum toxin A and/or dermal fillers].
AB  - BACKGROUND: More and more people worldwide and also in Germany are using
      botulinum toxin type A (BoNT-A) and hyaluronic acid injections for skin
      rejuvenation. OBJECTIVE: Study on body image and self-esteem of women with BoNT-A
      and/or hyaluronic acid filler treatment. MATERIAL AND METHODS: A total of 145
      women who requested BoNT-A and/or hyaluronic acid injections completed a survey
      comprised of the body dysmorphic disorder questionnaire, the Rosenberg self
      esteem scale and questionnaires on the attitudes and motives on measures for
      optimization of the body and demographic features. Using this instrument data on
      the body image and self-esteem as well as attitudes and motives for utilization
      of minimally invasive skin rejuvenation were collated. RESULTS: Female users of
      minimally invasive skin rejuvenation showed an overall higher socioeconomic
      status and an above average high monthly income. They lived in a partnership more
      often in comparison to women of equal age living in Berlin. The users of BoNT-A
      and/or hyaluronic acid fillers showed no conspicuous differences in body image
      and self-esteem. They showed a moderately positive attitude to body optimization
      procedures and 91% achieved their standard weight with a body mass index (BMI) of
      <=25 kg/m2 in comparison to 56% of German women in the same age range (25 to >=75
      years old). CONCLUSION: In the first study of body image and self-esteem in users
      of BoNT-A and/or dermal fillers in German women, the users showed no signs of
      body dysmorphic patterns or disorders of self-esteem.

PMID- 29052750
TI  - Impact of a CD4 gene haplotype on the immune response in minipigs.
AB  - The cluster of differentiation 4 (CD4) molecule functions as a co-receptor for
      MHC class II binding to TCR in T helper cells. A CD4 epitope deficiency was
      identified in the swine MeLiM (melanoblastoma-bearing Libechov minipig) strain, a
      model for spontaneous cutaneous melanoma development and regression. Extensive
      sequencing revealed a high genetic variability of CD4 and the existence of
      several haplotypes segregating in MeLiM. Forty polymorphisms were identified in
      the coding sequence, out of which 20 correspond to non-synonymous variants and 10
      are located in the 3'UTR of CD4 transcripts. One of the haplotypes segregating in
      the MeLiM explained the epitope deficiency observed. An association analysis
      between CD4 genotype and several phenotypes related to tumor regression was
      performed in 267 animals. An association was evidenced between a MeLiM
      alternative CD4 haplotype and skin and eye depigmentation, as well as the extent
      of hair depigmentation. Also, seric IgG concentration was shown to be higher in
      pigs carrying the alternative haplotype at the homozygous state. In conclusion,
      the genetic variability of the CD4 gene is associated with immune response
      related phenotypes in MeLiM minipigs.

PMID- 29052751
TI  - [Prevention of infections due to musculoskeletal allografts].
AB  - Transplantation of musculoskeletal tissues is widely used in the treatment of
      extensive defects of the musculoskeletal system, especially in orthopedics for
      exchange of prostheses, surgical interventions on the spine and in traumatology
      for reconstruction after extensive tumor resections. A danger after
      transplantation is the potential transmission of clinically relevant pathogens.
      Tissue banks have therefore established a safety level approach for
      musculoskeletal tissue transplants, which includes donor selection, laboratory
      testing, tissue procurement, tissue processing, tissue storage and quality
      assurance. In addition, inactivation procedures were also developed to protect
      the biological properties of the tissue and to guarantee a high microbiological
      safety against infections. Quality assurance in accordance with the Ordinance for
      the Production of Medicinal Products and Active Pharmaceutical Ingredients
      (AMWHV) and the Transplantation Act Tissue Regulations (TPG-GewV), ensures that
      the work of tissue banks conforms to the legal requirements. A new aspect is that
      the introduction of the single European code in April 2017, with which all
      transplants in Germany must be labelled, ensures the traceability of the tissue
      transplants after potential infections.

PMID- 29052752
TI  - [Fractures of the ankle joint in elderly patients].
AB  - The number of ankle fractures in elderly patients is increasing. The aim of
      treatment of ankle fractures in the elderly is to guarantee a possible unlimited
      autonomy and quality of life for patients. This is achieved by minimization of
      the complications and impairments after ankle joint fractures. Decisive for the
      further course is the initial treatment. The results are essentially determined
      by the soft tissue management, reduction and stable osteosynthesis; however, an
      orthogeriatric co-management with the implementation of treatment paths and
      standard operating procedures is recommended. The advantages of an
      interdisciplinary cooperation of trauma surgeons and geriatricians are obvious in
      this situation.

PMID- 29052753
TI  - Letter to the editor on "risk factors for complicated diverticulitis: systematic
      review and meta-analysis". What is the place of lateral internal partial
      sphincterotomy in the recurrent colonic diverticulitis treatment?

PMID- 29052754
TI  - Development of a method for the detection of polystyrene microplastics in
      paraffin-embedded histological sections.
AB  - The concerns about the presence of microplastics (MPs) in marine ecosystems have
      widely increased in the past years. This is reflected in a growing number of
      studies addressing the effects of exposure to these materials in indigenous,
      farmed and even laboratory marine animals subjected to toxicity-oriented
      bioassays. There have been, however, many constraints in the detection of MPs in
      biological tissues, as routine histological techniques tend to degrade these
      materials, which are especially sensitive to organic solvents. This issue hinders
      the application of standard histopathological procedures based on convenient
      paraffin wax-embedding protocols, with consequences for biomonitoring and
      bioassay procedures. The method described here was developed and validated for
      the detection of polystyrene microplastics in biological tissue processed for
      paraffin-based histology. The strategy was developed and tested from whole-soft
      body sections of marine mussels that internalised the MPs following dedicated
      bioassays. The protocol is based on the replacement of xylenes with isopropanol
      for the purpose of intermediate infiltration and deparaffinization. Special
      modifications for staining, mounting and archiving are needed and are detailed as
      well. The protocol is shown to be a highly cost- and time-effective procedure
      compatible with formalin-based fixatives plus standard sectioning and staining,
      yielding complete preservation of MPs and optimal tissue conditioning. The method
      also produced excellent results with pre-stained MPs, with fluorochromes
      included, altogether providing excellent localisation of polystyrene MPs in
      paraffin-processed biological tissue.

PMID- 29052755
TI  - Validation of an easily applicable three-dimensional immunohistochemical imaging
      method for a mouse brain using conventional confocal microscopy.
AB  - Histological analysis has been largely confined to two-dimensional analysis of
      thin tissue sections, hampering detailed understanding of three-dimensional
      cellular distribution in biological tissues. Tissue optical clearing methods
      enable three-dimensional histological analysis by rendering tissues transparent
      and suitable for microscopic detection of the fluorescent signals inside. Despite
      their great potential in histological research, the tissue clearing methods are
      not readily accessible to many researchers because of hazardous chemicals,
      complicated protocols and advanced microscopy. Furthermore, poor antibody
      penetration represents an additional major obstacle when performing three
      dimensional immunohistochemical studies. Here, we have examined tissue optical
      clearing of a mouse brain slice by a non-hazardous aqueous solution, ScaleA2. We
      modified the ScaleA2 solution by increasing the concentration of detergent. A
      simple immersion in the modified ScaleA2 solution alone enabled highly intense
      and uniform immunolabeling into deep tissues in three-dimensional immunostaining.
      Conventional confocal microscopy could image three-dimensional immunostaining of
      vasculature and astrocytes with fine processes to 1 mm imaging depth.
      Collectively, our technically straightforward clearing method will facilitate the
      common application of three-dimensional immunohistochemical analysis in many
      research fields including neuroscience, expanding our understanding of the
      detailed spatial cellular distribution underlying the physiology and pathology.

PMID- 29052756
TI  - Author Correction: Long working hours directly and indirectly (via short sleep
      duration) induce headache even in healthy white-collar men: cross-sectional and 1
      year follow-up analyses.
AB  - Author Correction: Int Arch Occup Environ Health DOI 10.1007/s00420-017-1255-6.

PMID- 29052757
TI  - Variation in occupational exposure associated with musculoskeletal complaints: a
      cross-sectional study among professional bassists.
AB  - BACKGROUND: Variation in occupational exposure is assumed to have a protective
      effect against the development of musculoskeletal complaints (MSC), but this
      common assumption is not strongly supported by the literature. Among musicians,
      who have a high prevalence of MSC, many play more than one type of instrument
      (multi-instrumentalism) for many hours a day. Since multi-instrumentalism implies
      greater variation in ergonomic load of specific musculoskeletal areas than mono
      instrumentalism, musicians are a suitable study population to test whether the
      above assumption is true. PURPOSE: To investigate in a sample of professional
      bass players whether multi-instrumentalists are less likely to have MSC than mono
      instrumentalists. METHODS: Participants were 141 professional and professional
      student double bassists and bass guitarists. Demographic, MSC and exposure
      characteristics were collected online with self-constructed and existing
      questionnaires. Logistic regression analysis was used to test the association
      between multi- versus mono-instrumentalism and MSC, adjusted for confounders.
      RESULTS: The prevalence of having MSC in the neck, back, right shoulder area and
      both wrist areas did not differ significantly between the two groups. Further
      analysis revealed that the likelihood of having MSC in the left shoulder area was
      higher in multi-instrumentalists compared to mono-instrumentalists (Odds ratio
      0.30, 95% CI 0.119-0.753, p = 0.010). CONCLUSION: In this sample of professional
      bass players, no protective effect of multi-instrumentalism against MSC was
      found. Multi-instrumentalism was associated with a higher prevalence of MSC in
      the left shoulder. This result challenges theoretical and clinical assumptions in
      occupational and pain medicine.

PMID- 29052758
TI  - Effects of trying 'not to move' instruction on cortical load and concurrent
      cognitive performance.
AB  - Motor and cognitive tasks often interfere when performed concurrently. The amount
      of interference typically scales with difficulty of the tasks involved. Thus,
      supposedly 'easy' motor tasks with restricted movement amplitude, like sitting on
      a chair, should show little or no interference with cognitive tasks at all. We
      measured the processing load induced by different postural tasks and their effect
      on cognitive performance under cognitive-motor dual-task conditions. Sixteen
      subjects performed postural motor tasks in three different positions: 'Lying in a
      sun lounger', 'Sitting on a bike saddle', and 'Upright on feet'. In each
      position, three different movement instructions were given; 'Stay stock-still',
      'Relax', 'Move easily'. Each combination of position and instruction was
      performed as single task but also in a dual-task condition with a concurrent
      calculation task. Brain activity in the right prefrontal cortex was monitored
      using functional near-infrared spectroscopy. The instruction to 'Stay stock
      still' produced higher cortical loads in single-task conditions for all positions
      compared to all other instructions. The calculation task induced additional brain
      activity in the same prefrontal area as the motor task. Calculation performance
      tended to be reduced in the 'Lying'-'Stay stock-still' condition. We discuss the
      relevance of these findings for learning scenarios in school.

PMID- 29052759
TI  - Telomerase regulation by the Pif1 helicase: a length-dependent effect?
AB  - Dysfunctional telomere length regulation is detrimental to human health, and both
      activation and inhibition of telomerase have been proposed in potential therapies
      to treat human diseases. The Saccharomyces cerevisiae Pif1 protein is an
      evolutionarily conserved helicase that inhibits telomerase activity at DNA ends.
      Recent studies have indicated that Pif1 is specifically important for inhibiting
      telomerase at DNA ends with very little or no telomeric sequence and at long
      telomeres. At the former, Pif1 prevents the inappropriate addition of a telomere
      at DNA double-strand breaks. For the latter, Pif1 has been shown to bind long
      telomeres to presumably promote the extension of the short ones. These
      observations leave the impression that Pif1 does not act at DNA ends with
      telomeric sequence of intermediate length. Here, we provide in vivo evidence that
      Pif1 inhibits telomerase activity at DNA ends regardless of telomere sequence
      length.

PMID- 29052760
TI  - Impact of plasmid architecture on stability and yEGFP3 reporter gene expression
      in a set of isomeric multicopy vectors in yeast.
AB  - Multicopy episomal plasmids in yeast, used whenever elevated levels of foreign or
      homologous gene expression are necessary, are known to be less stable compared to
      the endogenous 2-MUm plasmid they are based on, at least without selective
      pressure. Considering that rich medium favors growth rate and, simultaneously, is
      less expensive than selective medium, enhancing stability in non-selective medium
      is extremely desirable. In this study, we changed the architecture of a multicopy
      model expression plasmid, creating six isoforms (same size, same DNA content but
      different positions and orientations of the expression block) and studied mitotic
      stability, copy number, as well as reporter yEGFP3 expression between isoforms.
      With one isoform being significantly more stable than the others and another one
      exhibiting elevated plasmid copy numbers in rich medium, we show that
      consideration of the arrangement of the plasmid elements might be crucial for
      productivity employing Saccharomyces cerevisiae as a host. We strongly believe
      that the ideal architecture has to be assessed for each case and assembly
      strategy has to begin by evaluating the stability of the vector backbone before
      insertion of the desired gene. For the plasmid set studied, yEGFP3 reporter
      production depends more on mitotic stability than on elevated plasmid copy
      numbers in a small number of cells retaining the plasmid under non-selective
      conditions.

PMID- 29052762
TI  - [Life-threatening exophthalmos].

PMID- 29052761
TI  - Does surgical delay for radical prostatectomy affect biochemical recurrence? A
      retrospective analysis from a Canadian cohort.
AB  - AIM: We sought to explore the impact of surgical wait time (SWT) to robot
      assisted radical prostatectomy (RARP) on biochemical recurrence (BCR). METHOD:
      Retrospective review of a prospectively collected database between 2006 and 2015
      was conducted on all RARP cases. SWT was defined as period from prostate biopsy
      to surgery. Primary outcome was the impact on BCR, which was defined as two
      consecutive PSA >= 0.2 ng/dl, or salvage external beam radiation therapy and/or
      salvage androgen deprivation therapy. Patients were stratified according to
      D'Amico risk categories. Univariable analysis (UVA) and multivariable analyses
      (MVA) with a Cox proportional hazards regression model were used to evaluate the
      effect of SWT and other predictive factors on BCR, in each D'Amico risk group and
      on the overall collective sample. RESULTS: Patients eligible for analysis were
      619. Mean SWT was 153, 169, 150, and 125 days, for overall, low-, intermediate-,
      and high-risk patients, respectively. Multivariate analysis on the overall cohort
      did not show a significant relation between SWT and BCR. On subgroup analysis of
      D'Amico risk group, SWT was positively correlated to BCR for high-risk group (p =
      0.001). On threshold analysis, cut-off was found to be 90 days. SWT did not
      significantly affect BCR on UVA and MVA in the low- and intermediate-risk groups.
      CONCLUSION: Increased delay to surgery could affect the BCR, as there was a
      positive association in high-risk group. Further studies with longer follow-up
      are necessary to assess the impact of wait time on BCR, cancer specific survival
      and overall survival.

PMID- 29052763
TI  - [Laminar macular defects and pseudoholes : New classifications are necessary for
      individual treatment decisions].

PMID- 29052765
TI  - Assessment of different systems for the production of aldonic acids and sorbitol
      by calcium alginate-immobilized Zymomonas mobilis cells.
AB  - Equimolar amounts of lactobionic acid and sorbitol may be obtained in a reaction
      catalyzed by the enzymes glucose-fructose oxidoreductase and glucono-delta
      lactonase, which are found in the periplasm of Zymomonas mobilis. These reactions
      are generally conducted using immobilized bacterial cells, and the cell treatment
      and immobilization steps are costly and time-consuming. This study evaluated
      alternatives to simplify the preparation of calcium alginate-immobilized
      biocatalyst and its application in different operation modes and types of
      reactors. It was possible to eliminate cell permeabilization with
      cetyltrimethylammonium bromide, and the reticulation of Z. mobilis cells with
      glutaraldehyde sufficed to inhibit the fermentative metabolism of carbohydrates
      by the bacterium, with accumulation of bioconversion products. When the process
      was carried out in a mechanically stirred reactor in batch mode, 530 mmol L- 1 of
      products were obtained in 24 h. The process was also tested in fed-batch mode so
      as to use of a larger amount of lactose, since it could not be used in the batch
      because of its low solubility in water. Under this condition, final products
      concentration reached 745 mmol L- 1 within 42 h. Similar results were obtained
      for reactions conducted in a pneumatically stirred reactor in batch and fed-batch
      modes, proving the potential use of this process in several industrial settings.

PMID- 29052764
TI  - Fine mapping and candidate gene analysis of the virescent gene v 1 in Upland
      cotton (Gossypium hirsutum).
AB  - The young leaves of virescent mutants are yellowish and gradually turn green as
      the plants reach maturity. Understanding the genetic basis of virescent mutants
      can aid research of the regulatory mechanisms underlying chloroplast development
      and chlorophyll biosynthesis, as well as contribute to the application of
      virescent traits in crop breeding. In this study, fine mapping was employed, and
      a recessive gene (v 1) from a virescent mutant of Upland cotton was narrowed to
      an 84.1-Kb region containing ten candidate genes. The GhChlI gene encodes the
      cotton Mg-chelatase I subunit (CHLI) and was identified as the candidate gene for
      the virescent mutation using gene annotation. BLAST analysis showed that the
      GhChlI gene has two copies, Gh_A10G0282 and Gh_D10G0283. Sequence analysis
      indicated that the coding region (CDS) of GhChlI is 1269 bp in length, with three
      predicted exons and one non-synonymous nucleotide mutation (G1082A) in the third
      exon of Gh_D10G0283, with an amino acid (AA) substitution of arginine (R) to
      lysine (K). GhChlI-silenced TM-1 plants exhibited a lower GhChlI expression
      level, a lower chlorophyll content, and the virescent phenotype. Analysis of
      upstream regulatory elements and expression levels of GhChlI showed that the
      expression quantity of GhChlI may be normal, and with the development of the true
      leaf, the increase in the Gh_A10G0282 dosage may partially make up for the
      deficiency of Gh_D10G0283 in the v 1 mutant. Phylogenetic analysis and sequence
      alignment revealed that the protein sequence encoded by the third exon of GhChlI
      is highly conserved across diverse plant species, in which AA substitutions among
      the completely conserved residues frequently result in changes in leaf color in
      various species. These results suggest that the mutation (G1082A) within the
      GhChlI gene may cause a functional defect of the GhCHLI subunit and thus the
      virescent phenotype in the v1 mutant. The GhChlI mutation not only provides a
      tool for understanding the associations of CHLI protein function and the
      chlorophyll biosynthesis pathway but also has implications for cotton breeding.

PMID- 29052766
TI  - Decreased diabetes risk over 9 year after 18-month oral L-arginine treatment in
      middle-aged subjects with impaired glucose tolerance and metabolic syndrome
      (extension evaluation of L-arginine study).
AB  - PURPOSE: This study aimed to determine whether L-arginine supplementation lasting
      for 18 months maintained long-lasting effects on diabetes incidence, insulin
      secretion and sensitivity, oxidative stress, and endothelial function during 108
      months among subjects at high risk of developing type 2 diabetes. METHODS: One
      hundred and forty-four middle-aged subjects with impaired glucose tolerance and
      metabolic syndrome were randomized in 2006 to an L-arginine supplementation (6.4
      g orally/day) or placebo therapy lasting 18 months. This period was followed by a
      90-month follow-up. The primary outcome was a diagnosis of diabetes during the
      108 month study period. Secondary outcomes included changes in insulin secretion
      (proinsulin/c-peptide ratio), insulin sensitivity (IGI/HOMA-IR), oxidative stress
      (AOPPs), and vascular function. After the 18 month participation, subjects that
      were still free of diabetes and willing to continue their participation (104
      subjects) were further followed until diabetes diagnosis, with a time span of
      about 9 years from baseline. RESULTS: Although results derived from the 18 month
      of the intervention study demonstrated no differences in the probability of
      becoming diabetics, at the end of the study, the cumulative incidence of diabetes
      was of 40.6% in the L-arginine group and of 57.4% in the placebo group. The
      adjusted HR for diabetes (L-arginine vs. placebo) was 0.66; 95% CI 0.48, 0.91; p
      < 0.02). Proinsulin/c-peptide ratio (p < 0.001), IGI/HOMA-IR (p < 0.01), and AOPP
      (p < 0.05) levels were ameliorated in L-arginine compared to placebo.
      CONCLUSIONS: These results may suggest that the administration of L-arginine
      could delay the development of T2DM for a long period. This effect could be
      mediated, in some extent, by L-arginine-induced reduction in oxidative stress.

PMID- 29052767
TI  - Acute regulation of multidrug resistance-associated protein 2 localization and
      activity by cAMP and estradiol-17beta-D-glucuronide in rat intestine and Caco-2
      cells.
AB  - Multidrug resistance-associated protein 2 (MRP2) is an ATP-dependent transporter
      expressed at the brush border membrane of the enterocyte that confers protection
      against absorption of toxicants from foods or bile. Acute, short-term regulation
      of intestinal MRP2 activity involving changes in its apical membrane localization
      was poorly explored. We evaluated the effects of dibutyryl-cAMP (db-cAMP), a
      permeable analog of cAMP, and estradiol-17beta-D-glucuronide (E217G), an
      endogenous derivative of estradiol, on MRP2 localization and activity using
      isolated rat intestinal sacs and Caco-2 cells, a model of human intestinal
      epithelium. Changes in MRP2 localization were studied by Western blotting of
      plasma membrane (PM) vs. intracellular membrane (IM) fractions in both
      experimental models, and additionally, by confocal microscopy in Caco-2 cells.
      After 30 min of exposure, db-cAMP-stimulated sorting of MRP2 from IM to PM both
      in rat jejunum and Caco-2 cells at 10 and 100 uM concentrations, respectively,
      with increased excretion of the model substrate 2,4-dinitrophenyl-S-glutathione.
      In contrast, E217G (400 uM) induced internalization of MRP2 together with
      impairment of transport activity. Confocal microscopy analysis performed in Caco
      2 cells confirmed Western blot results. In the particular case of E217G, MRP2
      exhibited an unusual pattern of staining compatible with endocytic vesiculation.
      Use of selective inhibitors demonstrated the participation of cAMP-dependent
      protein kinase and classic calcium-dependent protein kinase C in db-cAMP and
      E217G effects, respectively. We conclude that localization of MRP2 in intestine
      may be subjected to a dynamic equilibrium between plasma membrane and
      intracellular domains, thus allowing for rapid regulation of MRP2 function.

PMID- 29052768
TI  - Phylogenetic trophic specialization: a robust comparison of herbivorous guilds.
AB  - Resource specialization is a key concept in ecology, but it is unexpectedly
      difficult to parameterize. Differences in resource availability, sampling effort
      and abundances preclude comparisons of incompletely sampled biotic interaction
      webs. Here, we extend the distance-based specialization index (DSI) that measures
      trophic specialization by taking resource phylogenetic relatedness and
      availability into account into a rescaled version, DSI*. It is a versatile metric
      of specialization that expands considerably the scope and applicability, hence
      the usefulness, of DSI. The new metric also accounts for differences in abundance
      and sampling effort of consumers, which enables robust comparisons among distinct
      guilds of consumers. It also provides an abundance threshold for the reliability
      of the metric for rare species, a very desirable property given the difficulty of
      assessing any aspect of rare species accurately. We apply DSI* to an extensive
      dataset on interactions between insect herbivores from four folivorous guilds and
      their host plants in Papua New Guinean rainforests. We demonstrate that DSI*,
      contrary to the original DSI, is largely independent of sample size and weakly
      and non-linearly related with several host specificity measures that do not
      adjust for plant phylogeny. Thus, DSI* provides further insights into host
      specificity patterns; moreover, it is robust to the number and phylogenetic
      diversity of plant species selected to be sampled for herbivores. DSI* can be
      used for a broad range of comparisons of distinct feeding guilds, geographical
      locations and ecological conditions. This is a key advance in elucidating the
      interaction structure and evolution of highly diversified systems.

PMID- 29052769
TI  - Terpenoid biosynthesis in Arabidopsis attacked by caterpillars and aphids:
      effects of aphid density on the attraction of a caterpillar parasitoid.
AB  - One of the responses of plants to insect attack is the production of volatile
      organic compounds that mediate indirect defence of plants by attracting natural
      enemies of the attacking herbivores. Herbivore-induced plant volatiles (HIPVs)
      include terpenoids that play key roles in the attraction of natural enemies.
      Crosstalk between phytohormonal signalling pathways is well known to affect the
      regulation of plant defences, including the emission of HIPVs. Thus, simultaneous
      feeding on the same plant by caterpillars and aphids, can affect the attraction
      of parasitoids by the plant compared to single insect attack. The role of aphid
      density in the regulation of HIPV emission by plants under dual attack has not
      been studied previously. Here, we investigated the attraction of Diadegma
      semiclausum, a parasitoid of the Diamondback moth Plutella xylostella, to
      volatiles emitted by Arabidopsis thaliana plants, simultaneously attacked by host
      caterpillars, and by the non-host aphid Brevicoryne brassicae. Our study shows
      that the effect of aphid infestation on parasitoid attraction is influenced by
      the density of the aphids. Biosynthesis and emission of (E,E)-alpha-farnesene
      could be linked to the observed preference of D. semiclausum parasitoids for the
      HIPV blend emitted by plants dually infested by caterpillars and aphids at a high
      density compared to dually infested plants with a low aphid density. Parasitoids
      such as D. semiclausum are important enemies of herbivorous insects and a better
      understanding of how plants express indirect defence mechanisms in response to
      multiple insect attack will provide important knowledge on plant-herbivore
      parasitoid interactions under multiple stress conditions.

PMID- 29052770
TI  - Extrapulmonary involvement in pediatric tuberculosis.
AB  - Tuberculosis in childhood is clinically challenging, but it is a preventable and
      treatable disease. Risk factors depend on age and immunity status. The most
      common form of pediatric tuberculosis is pulmonary disease, which comprises more
      than half of the cases. Other forms make up the extrapulmonary tuberculosis that
      involves infection of the lymph nodes, central nervous system, gastrointestinal
      system, hepatobiliary tree, and renal and musculoskeletal systems. Knowledge of
      the imaging characteristics of pediatric tuberculosis provides clues to
      diagnosis. This article aims to review the imaging characteristics of common
      sites for extrapulmonary tuberculous involvement in children.

PMID- 29052771
TI  - Standardized radiographic interpretation of thoracic tuberculosis in children.
AB  - There is a lack of standardized approach and terminology to classify the diverse
      spectrum of manifestations in tuberculosis. It is important to recognize the
      different clinical and radiographic patterns to guide treatment. As a result of
      changing epidemiology, there is considerable overlap in the radiologic
      presentations of primary tuberculosis and post-primary tuberculosis. In this
      article we promote a standardized approach in clinical and radiographic
      classification for children suspected of having or diagnosed with childhood
      tuberculosis. We propose standardized terms to diminish confusion and
      miscommunication, which can affect management. In addition, we present pitfalls
      and limitations of imaging.

PMID- 29052772
TI  - Imaging of thoracic tuberculosis in children: current and future directions.
AB  - Tuberculosis continues to be an important cause of morbidity and mortality
      worldwide. It is the leading cause of infection-related deaths worldwide.
      Children are amongst the high-risk groups for developing tuberculosis and often
      pose a challenge to the clinicians in making a definitive diagnosis. The newly
      released global tuberculosis report from World Health Organization reveals a 50%
      increase in fatality from tuberculosis in children. Significantly, diagnostic and
      treatment algorithms of tuberculosis for children differ from those of adults.
      Bacteriologic confirmation of the disease is often difficult in children; hence
      radiologists have an important role to play in early diagnosis of this disease.
      Despite advancing technology, the key diagnostic imaging modalities for primary
      care and emergency services, especially in rural and low-resource areas, are
      chest radiography and ultrasonography. In this article, we discuss various
      diagnostic imaging modalities used in diagnosis and treatment of tuberculosis and
      their indications. We highlight the use of US as point-of-care service along with
      mediastinal US and rapid MRI protocols, especially in mediastinal lymphadenopathy
      and thoracic complications. MRI is the ideal modality in high-resource areas when
      adequate infrastructure is available. Because the prevalence of tuberculosis is
      highest in lower-resource countries, we also discuss global initiatives in low
      resource settings.

PMID- 29052773
TI  - A systemic review of tuberculosis with HIV coinfection in children.
AB  - The epidemiology of tuberculosis is adversely impacted by the human
      immunodeficiency virus (HIV) coinfection. HIV-infected patients are more prone to
      opportunistic infections, most commonly tuberculosis, and the risk of death in
      coinfected patients is higher than in those without HIV. Due to the impaired
      cellular immunity and reduced immunological response in HIV-infected patients,
      the classic imaging features of tuberculosis usually seen in patients without HIV
      may present differently. The aim of this review article is to highlight the
      imaging features that may assist in the diagnosis of tuberculosis in patients
      with HIV coinfection.

PMID- 29052774
TI  - Intrathoracic tuberculous lymphadenopathy in children: a guide to chest
      radiography.
AB  - Making the diagnosis of pulmonary tuberculosis in children can be difficult
      because microbiological confirmation is not often achieved. Diagnosis is
      therefore often based on clinical features in combination with chest radiograph
      findings. Chest radiographs can demonstrate lymphadenopathy of the hilar and para
      tracheal regions on the anteroposterior view, and subcarinal lymphadenopathy on
      the lateral view. However poor interobserver agreement has been reported for
      radiologist and clinician assessment of lymphadenopathy. This might reflect the
      lack of standardised imaging criteria for diagnosis as well as radiologists'
      objectives for achieving sensitivity rather than specificity. In this paper the
      authors provide a pictorial aid of chest radiographs in children with culture
      confirmed tuberculosis to help clinicians identify lymph node enlargement in
      primary pulmonary tuberculosis. This collection of images comprises chest
      radiographs accompanied by schematics and either CT or MRI scan confirmation of
      pathological lymph node enlargement at the positions commonly affected in
      tuberculosis.

PMID- 29052775
TI  - Revisiting and redefining the standards in tuberculosis imaging.

PMID- 29052780
TI  - Immunotherapy for hepatocellular carcinoma patients: is it ready for prime time?
AB  - Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and
      the second most common cause of cancer death worldwide. Current treatment options
      for patients with intermediate and advanced HCC are limited, and there is an
      unmet need for novel therapeutic approaches. HCC is an attractive target for
      immunomodulation therapy, since it arises in an inflammatory milieu due to
      hepatitis B and C infections and cirrhosis. However, a major barrier to the
      development and success of immunotherapy in patients with HCC is the liver's
      inherent immunosuppressive function. Recent advances in the field of cancer
      immunology allowed further characterization of immune cell subsets and function,
      and created new opportunities for therapeutic modulation of the immune system. In
      this review, we present the different immune cell subsets involved in potential
      immune modulation of HCC, discuss their function and clinical relevance, review
      the variety of immune therapeutic agents currently under investigation in
      clinical trials, and outline future research directions.

PMID- 29052781
TI  - Absolute lymphocyte counts at end of induction correlate with distinct immune
      cell compartments in pediatric B cell precursor acute lymphoblastic leukemia.
AB  - Several retrospective studies in children with B cell precursor (BCP) acute
      lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute
      lymphocyte counts (ALC) early into treatment significantly correlated with
      improved relapse-free and overall survival. It still remains unknown, however,
      whether the predictive role of higher ALCs reflects general bone marrow recovery
      or a more specific attribute of immune function. To investigate this question, we
      implemented a prospective observational cohort study in 20 children with BCP ALL
      on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T,
      B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells)
      compartments. In a first evaluation of a cohort treated with Children's Oncology
      Group-based induction chemotherapy, the immune cell compartments were
      differentially depleted at D29. Neither gender, risk status, minimal residual
      disease, nor bone marrow recovery markers correlated with D29 ALC. In contrast,
      both CD3+ T cell and dendritic cell compartments, which did not correlate with
      age, significantly correlated with D29 ALC (p < 0.0001). In addition, subset
      complexity of cellular immune compartments was preserved at D29. This study
      reveals that D29 ALC significantly correlates with distinct immune cell
      compartments but not with bone marrow recovery markers, suggesting that higher
      D29 ALCs may contribute to leukemia control by inducing specific host immune
      activity.

PMID- 29052783
TI  - Anatomical study of the left superior mediastinal lymphatics for tracheal
      branches of left recurrent laryngeal nerve-preserving mediastinoscope-assisted
      surgery in esophageal cancer.
AB  - PURPOSE: Curative treatment of esophageal cancer requires meticulous superior
      mediastinal lymphadenectomy, in addition to esophagectomy, because superior
      mediastinal lymph node metastases are common in esophageal cancer. When
      preserving the tracheal branches of the left recurrent laryngeal nerve (RLN),
      good anatomical understanding is required for confirmation of the positional
      relationships between the courses of lymphatic vessels, lymph node distribution,
      and the left RLN and its tracheal branches. We performed a detailed anatomical
      examination of these relationships. METHODS: Macroscopic anatomical observation
      and histological examination was performed on cadavers. In addition to
      hematoxylin and eosin staining, immunostaining using antipodoplanin antibody D2
      40 (podoplanin) was performed to identify the lymphatic vessels. RESULTS: The
      tracheal branches of the left RLN were clearly observed, but no lymphatic vessels
      crossing the ventral or dorsal side of the branches were identified either macro
      anatomically or histologically. CONCLUSION: No complex lymphatic network
      structure straddling the plane composed of tracheal branches of the left RLN was
      found in the left superior mediastinum. This suggests that dissection of the
      lymph nodes around the left RLN via the pneumomediastinum method using the left
      cervical approach may allow preservation of the tracheal branches of the left RLN
      by maintaining dissection accuracy.

PMID- 29052782
TI  - Clinical and immunologic evaluation of three metastatic melanoma patients treated
      with autologous melanoma-reactive TCR-transduced T cells.
AB  - Malignant melanoma incidence has been increasing for over 30 years, and despite
      promising new therapies, metastatic disease remains difficult to treat. We
      describe preliminary results from a Phase I clinical trial (NCT01586403) of
      adoptive cell therapy in which three patients received autologous CD4+ and CD8+ T
      cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a
      marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR
      produces functional responses in both CD4+ and CD8+ T cells. Parameters monitored
      on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3,
      CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial,
      T cells were activated, transduced, selected for CD34t+ cells, then re-activated,
      and expanded in IL-2 and IL-15. After lymphodepleting chemotherapy, patients were
      given transduced T cells and IL-2, and were followed for clinical and biological
      responses. Transduced T cells were detected in the circulation of three treated
      patients for the duration of observation (42, 523, and 255 days). Patient 1
      tolerated the infusion well but died from progressive disease after 6 weeks.
      Patient 2 had a partial response by RECIST criteria then progressed. After
      progressing, Patient 2 was given high-dose IL-2 and subsequently achieved
      complete remission, coinciding with the development of vitiligo. Patient 3 had a
      mixed response that did not meet RECIST criteria for a clinical response and
      developed vitiligo. In two of these three patients, adoptive transfer of
      tyrosinase-reactive TCR-transduced T cells into metastatic melanoma patients had
      clinical and/or biological activity without serious adverse events.

PMID- 29052785
TI  - Erratum to: C3 glomerulopathy and current dilemmas.
AB  - The article, "C3 glomerulopathy and current dilemmas", written by Naoko Ito,
      Ryuji Ohashi and Michio Nagata was originally published electronically on the
      publisher's internet portal (currently SpringerLink) on November 23, 2016 without
      open access.

PMID- 29052784
TI  - Exercise and bone health across the lifespan.
AB  - With ageing, bone tissue undergoes significant compositional, architectural and
      metabolic alterations potentially leading to osteoporosis. Osteoporosis is the
      most prevalent bone disorder, which is characterised by progressive bone
      weakening and an increased risk of fragility fractures. Although this metabolic
      disease is conventionally associated with ageing and menopause, the predisposing
      factors are thought to be established during childhood and adolescence. In light
      of this, exercise interventions implemented during maturation are likely to be
      highly beneficial as part of a long-term strategy to maximise peak bone mass and
      hence delay the onset of age- or menopause-related osteoporosis. This notion is
      supported by data on exercise interventions implemented during childhood and
      adolescence, which confirmed that weight-bearing activity, particularly if
      undertaken during peripubertal development, is capable of generating a
      significant osteogenic response leading to bone anabolism. Recent work on human
      ageing and epigenetics suggests that undertaking exercise after the fourth decade
      of life is still important, given the anti-ageing effect and health benefits
      provided, potentially occurring via a delay in telomere shortening and
      modification of DNA methylation patterns associated with ageing. Exercise is
      among the primary modifiable factors capable of influencing bone health by
      preserving bone mass and strength, preventing the death of bone cells and anti
      ageing action provided.

PMID- 29052786
TI  - Tolvaptan promotes urinary excretion of sodium and urea: a retrospective cohort
      study.
AB  - BACKGROUND: Tolvaptan (TLV) promotes aquaresis; however, little is known about
      its effect on solute excretion in chronic kidney disease (CKD). METHODS: We
      retrospectively studied CKD patients with decompensated heart failure (HF) or
      those with autosomal dominant polycystic kidney disease (ADPKD) receiving TLV.
      Patients with an increased urine volume of more than twice of daily variance were
      defined as "responders" in HF. We compared the ability of the urinary osmolality
      (U-OSM) change and urinary creatinine concentration ([U-Cr]) change to
      discriminate "responders". The fractional excretion of sodium (FeNa) and urea
      nitrogen (FeUN), and blood urea nitrogen (BUN) were monitored. RESULTS: In 30
      responders among 53 HF patients, TLV increased FeUN significantly from 36.1 to
      44.2% after starting TLV, but not FeNa. Since U-OSM is determined partially by
      urinary UN concentration, the decrease of [U-Cr] after treatment outperformed the
      U-OSM decrement to discriminate responders, as shown in receiver operating
      characteristic curve analysis and significantly higher net reclassification
      index. In 13 ADPKD patients, TLV increased FeUN (34.8, 47.3%, p = 0.02), and
      significant decrease of BUN by 2.3 (95% confidence interval 0.4-4.2) mg/dL was
      observed even 3 months after the intervention. Systolic blood pressure decreased
      significantly by 14.2 (95% confidence interval 4.0-24.4) mmHg along with the
      increase in FeNa, leading to reduced dosage of antihypertensives in 6 patients.
      CONCLUSION: TLV promotes the excretion of sodium and urea. The change in [U-Cr]
      is useful for early discrimination of responders. Hypotension should be carefully
      monitored during high-dose TLV therapy.

PMID- 29052787
TI  - Pentapeptide-insertion scanning mutational analysis of turkey herpesvirus HVT063
      reveals residues important for its RNA silencing suppression activity.
AB  - HVT063, an RNA-binding protein encoded by turkey herpesvirus, has been shown
      previously to suppress RNA silencing. Here, a scanning library produced by
      pentapeptide-insertion scanning mutagenesis was used to identify key residues
      associated with its RNA silencing suppressor (RSS) activity. Forty-two in-frame
      insertion mutants of HVT063 protein were evaluated for their RSS activity using
      the dual-luciferase transient expressing assay system. Sixteen mutations resulted
      in a loss of RSS activity, 20 mutations resulted in decreased RSS activity, and
      six mutations exhibited high RSS activity similar to wild-type HVT063. Based on a
      three-dimensional structure prediction, most of the loss-of-function mutations
      were located around a predominantly alpha-helical region at the C-terminal end of
      HVT063. In particular, a conserved domain in this region, named herpes_UL69,
      showed low tolerance for five-amino-acid insertions. Combined with the results of
      our previous studies, basic amino acids could play a key role in RSS activity.
      These results also demonstrate that pentapeptide-insertion scanning mutagenesis
      combined with dual-luciferase assays is an effective method to functionally
      characterize RSSs.

PMID- 29052788
TI  - Sequence analysis of six full-length bean yellow mosaic virus genomes reveals
      phylogenetic diversity in India strains, suggesting subdivision of phylogenetic
      group-IV.
AB  - We report the complete genome sequence of five bean yellow mosaic virus (BYMV)
      isolates (CK-GL1, CK-GL3, CK-GL4, CK-GL5 and Vfaba2) that share 74.6-98.9%
      (nucleotide) and 81.5-99.1% (amino acid) identity with globally available BYMV
      sequences. Phylogenetic analysis clustered them specifically in BYMV phylogenetic
      group-IV within the existing nine groups. The CK-GL1, CK-GL2, CK-GL4 and CK-GL5
      isolates formed a discrete cluster within group-IV. The present study suggests
      subdivision of group-IV into subgroup-IVa and IVb. Moreover, infectivity assays
      using in vitro RNA transcripts from subgroup-IVa (CK-GL3 isolate) and IVb (CK-GL1
      isolate) showed distinct biological differences between the isolates supporting
      subdivision.

PMID- 29052789
TI  - Computational Analysis of Pharyngeal Swallowing Mechanics in Patients with Motor
      Neuron Disease: A Pilot Investigation.
AB  - Swallowing impairment (dysphagia) is a common sequela in patients with motor
      neuron disease (MND). The purpose of this retrospective, observational pilot
      investigation was to characterize how pharyngeal swallowing mechanics are
      impacted in patients with MND using a comparison with healthy, non-dysphagic
      control group. Computational analysis of swallowing mechanics (CASM) was used to
      determine covariate biomechanics of pharyngeal swallowing from videofluoroscopic
      assessment in 15 patients with MND and 15 age- and sex-matched healthy controls.
      Canonical variant analysis with post hoc discriminate function analysis (DFA) was
      performed on coordinate data mapping functional muscle groups underlying
      pharyngeal swallowing. Differences in swallowing mechanics associated with group
      (MND; control), motor neuron predominance (upper; lower), onset (bulbar; spinal),
      and swallow task (thin, pudding) were evaluated and visualized. Pharyngeal
      swallowing mechanics differed significantly in patients with MND compared with
      healthy controls (D = 2.01, p < 0.0001). Post hoc DFA pairwise comparisons
      suggest differences in pharyngeal swallow mechanics by motor neuron predominance
      (D = 5.03, p < 0.0001), onset (D = 2.03, p < 0.0001), and swallow task (D = 1.04,
      p < 0.0001). Pharyngeal swallowing mechanics of patients with MND differ from and
      are more heterogeneous than healthy controls. These findings suggest patients
      with MND may compensate reductions in pharyngeal shortening and tongue base
      retraction by extending the head and neck and increasing hyolaryngeal excursion.
      This work and further CASM investigations will lead to further insights into
      development and evaluation of targeted clinical treatments designed to prolong
      safe and efficient swallowing function in patients with MND.

PMID- 29052790
TI  - Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients
      with prior DAA experience, severe renal impairment, or genotype 3 infection.
AB  - BACKGROUND: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A
      protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated
      pangenotypic activity and high sustained virologic response (SVR) rates in
      studies outside Japan. Here we report safety and efficacy in a subset of Japanese
      patients with chronic HCV infection who received G/P 300/120 mg in a phase 3,
      open-label, multicenter study (CERTAIN-1). METHODS: This analysis focuses on
      three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to
      achieve SVR after treatment with a direct acting antiviral (DAA)-containing
      regimen; GT1/2-infected patients with severe renal impairment (estimated
      glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients.
      Patients in the renal impairment and GT3 cohorts were treatment-naive or
      interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naive patients
      in the renal impairment cohort received G/P for 8 weeks; all other patients were
      treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post
      treatment (SVR12). RESULTS: The study enrolled 33 GT1/2-infected patients who
      failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients
      with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients
      (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and
      10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload,
      not related to G/P) occurred in a patient on chronic intermittent hemodialysis.
      CONCLUSIONS: G/P achieved high SVR12 rates and was well tolerated in three
      difficult-to-treat patient subgroups with limited treatment options in Japan (DAA
      experienced patients, patients with severe renal impairment, and GT3-infected
      patients). These results support the potential suitability of this regimen for
      these special populations in Japan.

PMID- 29052791
TI  - Potential diagnostic performance of contrast-enhanced ultrasound and tumor
      markers in differentiating combined hepatocellular-cholangiocarcinoma from
      hepatocellular carcinoma and cholangiocarcinoma.
AB  - PURPOSE: To evaluate the diagnostic performance of the combination of tumor
      markers [alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9)] and
      imaging features in differentiating combined hepatocellular-cholangiocarcinoma
      (CHC) from hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). METHODS:
      Forty consecutive patients with pathologically proven CHC were retrospectively
      evaluated with contrast-enhanced ultrasound (CEUS). Additionally, 40 HCC and 40
      CC patients who were randomly selected from the same period served as a control
      group. Images were classified as HCC-like or CC-like pattern according to CEUS
      guidelines recommended by World and European Federation for Ultrasound in
      Medicine and Biology (WFUMB-EFSUMB). The diagnostic criteria of CHC were defined
      as follows: (1) both AFP and CA19-9 are simultaneously elevated (AFP > 20 ng/ml
      and CA19-9 > 100 units/ml); or (2) elevated AFP with a CC-like pattern on CEUS
      and without elevated CA19-9 level; or (3) elevated CA19-9 with an HCC-like
      pattern on CEUS and without elevated AFP level. The diagnostic tests were
      performed with calculation of the sensitivity, specificity, accuracy, positive
      predictive value (PPV), negative predictive value (NPV), and area under the
      receiver operating characteristic curve (AUC). RESULTS: For the 40 CHC patients,
      the rates of elevated AFP and CA19-9 serology were 55.0 and 30.0%, respectively.
      Twenty-three (57.5%) patients exhibited an HCC-like pattern, and 15 (37.5%)
      showed a CC-like pattern. After applying the above diagnostic criteria of CHC in
      the 120 patients, the sensitivity, specificity, PPV, NPV, accuracy, and AUC were
      32.5, 93.8, 72.2, 73.5, 73.3, and 0.631%, respectively. When the actual
      prevalence rate (0.4-14.3%) was taken into account, the PPV and NPV were modified
      from 2.1 to 46.7% and 89.3 to 99.7%, respectively. CONCLUSION: The combination of
      enhancement patterns on CEUS and serum tumor markers (AFP and CA19-9) may be a
      potentially specific diagnostic method to differentiate CHC from HCC and CC.

PMID- 29052792
TI  - Prediction of binding poses to FXR using multi-targeted docking combined with
      molecular dynamics and enhanced sampling.
AB  - Advanced molecular docking methods often aim at capturing the flexibility of the
      protein upon binding to the ligand. In this study, we investigate whether instead
      a simple rigid docking method can be applied, if combined with multiple target
      structures to model the backbone flexibility and molecular dynamics simulations
      to model the sidechain and ligand flexibility. The methods are tested for the
      binding of 35 ligands to FXR as part of the first stage of the Drug Design Data
      Resource (D3R) Grand Challenge 2 blind challenge. The results show that the
      multiple-target docking protocol performs surprisingly well, with correct poses
      found for 21 of the ligands. MD simulations started on the docked structures are
      remarkably stable, but show almost no tendency of refining the structure closer
      to the experimentally found binding pose. Reconnaissance metadynamics enhances
      the exploration of new binding poses, but additional collective variables
      involving the protein are needed to exploit the full potential of the method.

PMID- 29052793
TI  - Comparison of fracture risk assessment tools in older men without prior hip or
      spine fracture: the MrOS study.
AB  - : Femoral neck bone mineral density (BMD), age plus femoral neck BMD T score, and
      three externally generated fracture risk tools had similar accuracy to identify
      older men who developed osteoporotic fractures. Risk tools with femoral neck BMD
      performed better than those without BMD. The externally developed risk tools were
      poorly calibrated. INTRODUCTION: We compared the performance of fracture risk
      assessment tools in older men, accounting for competing risks including
      mortality. METHODS: A comparative ROC curve analysis assessed the ability of the
      QFracture, FRAX(r) and Garvan fracture risk tools, and femoral neck bone mineral
      density (BMD) T score with or without age to identify incident fracture in
      community-dwelling men aged 65 years or older (N = 4994) without hip or clinical
      vertebral fracture or antifracture treatment at baseline. RESULTS: Among risk
      tools calculated with BMD, the discriminative ability to identify men with
      incident hip fracture was similar for FRAX (AUC 0.77, 95% CI 0.73, 0.81), the
      Garvan tool (AUC 0.78, 95% CI 0.74, 0.82), age plus femoral neck BMD T score (AUC
      0.79, 95% CI 0.75, 0.83), and femoral neck BMD T score alone (AUC 0.76, 95% CI
      0.72, 0.81). Among risk tools calculated without BMD, the discriminative ability
      to identify hip fracture was similar for QFracture (AUC 0.69, 95% CI 0.66, 0.73),
      FRAX (AUC 0.70, 95% CI 0.66, 0.73), and the Garvan tool (AUC 0.71, 95% CI 0.67,
      0.74). Correlated ROC curve analyses revealed better diagnostic accuracy for risk
      scores calculated with BMD compared with QFracture (P < 0.0001). Calibration was
      good for the internally generated BMD T score predictor with or without age and
      poor for the externally developed risk tools. CONCLUSION: In untreated older men
      without fragility fractures at baseline, an age plus femoral neck BMD T score
      classifier identified men with incident hip fracture as accurately as more
      complicated fracture risk scores.

PMID- 29052794
TI  - Mn K-edge X-ray absorption studies of mononuclear Mn(III)-hydroxo complexes.
AB  - Mn K-edge X-ray absorption spectroscopy experiments were performed on the solid-
      and solution-phase samples of [MnII(dpaqR)](OTf) (R=H, Me) and
      [MnIII(OH)(dpaqR)](OTf). The extended X-ray absorption fine structure (EXAFS)
      data show distinct differences between the MnII and MnIII-OH complexes, with fits
      providing metric parameters in excellent agreement with values from X-ray
      crystallography and density functional theory (DFT) computations. Evaluation of
      the EXAFS data for solid-phase [MnIII(OH)(dpaq)](OTf) resolved a short Mn-OH bond
      distance of 1.79 A; however, the short trans-amide nitrogen bond of the
      supporting ligand precluded the resolution of the Mn-OH bond distance in the
      corresponding solution-phase sample and for both [MnIII(OH)(dpaqMe)](OTf)
      samples. The edge energy also increases by approximately 2 eV from the MnII to
      the MnIII-OH complexes. Experimental pre-edge analysis shows the MnII complexes
      to have pre-edge areas comparable to the MnIII-OH complexes, despite the presence
      of the relatively short Mn-OH distance. Time-dependent density functional theory
      (TD-DFT) computations illustrate that Mn 3d-4p mixing, a primary contributor to
      pre-edge intensities, decreases by ~ 0.3% from the MnII to MnIII-OH complexes,
      which accounts for the very similar pre-edge areas. Collectively, this work shows
      that combined EXAFS and XANES analysis has great potential for identification of
      reactive MnIII-OH intermediates, such as those proposed in enzyme active sites.

PMID- 29052795
TI  - Effects of glutamine, taurine and their association on inflammatory pathway
      markers in macrophages.
AB  - The immune system is essential for the control and elimination of infections, and
      macrophages are cells that act as important players in orchestrating the various
      parts of the inflammatory/immune response. Amino acids play important role in
      mediating functionality of the inflammatory response, especially mediating
      macrophages functions and cytokines production. We investigated the influence of
      glutamine, taurine and their association on the modulation of inflammatory
      pathway markers in macrophages. The RAW 264.7 macrophage cell line was cultivated
      in the presence of glutamine and taurine and proliferation rates, cell viability,
      cell cycle phases, IL-1alpha, IL-6, IL-10 and TNF-alpha as well as H2O2
      production and the expression of the transcription factor, NFkappaB, and its
      inhibitor, IkappaBalpha, were evaluated. Our results showed an increase in viable
      cells and increased proliferation rates of cells treated with glutamine
      concentrations over 2 mM, as well as cells treated with both glutamine and
      taurine. The cell cycle showed a higher percentage of cells in the phases S, G2
      and M when they were treated with 2 or 10 mM glutamine, or with glutamine and
      taurine in cells stimulated with lipopolysaccharide. The pNFkappaB/NFkappaB
      showed reduced ratio expression when cells were treated with 10 mM of glutamine
      or with glutamine in association with taurine. These conditions also resulted in
      reduced TNF-alpha, IL-1alpha and H2O2 production, and higher production of IL-10.
      These findings demonstrate that glutamine and taurine are able to modulate
      macrophages inflammatory pathways, and that taurine can potentiate the effects of
      glutamine, illustrating their immunomodulatory properties.

PMID- 29052796
TI  - Medical management of Salmonella enteritidis prosthetic valve endocarditis with
      multiple infectious foci.

PMID- 29052797
TI  - Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint
      infections: a retrospective study of 78 patients.
AB  - PURPOSE: This study aimed at describing the use of oral cyclines (i.e.,
      doxycycline and minocycline) as suppressive antibiotic therapy (SAT) in patients
      with periprosthetic joint infections (PJIs). METHODS: Medical charts of all
      patients with surgical revisions for PJIs who were given cycline-based SAT
      because of a high failure of various origins were reviewed. Data regarding
      tolerability and effectiveness of cycline-based SAT were analysed. RESULTS:
      Seventy-eight patients of mean age 64 +/- 17 years received cycline-base SAT in
      the period from January 2006 to January 2014. PJIs involved the knee in 37
      patients (47%), the hip in 35 (45%), the elbow in 4 (5%), and the shoulder in 2
      (3%) and were qualified as early in 31 patients (39.7%). Staphylococcus spp. were
      the most common pathogens accounting for 72.1% of the total number of bacterial
      strains identified. All included patients had surgery which consisted in
      debridement and implant retention in 59 of them (75.6%). Doxycycline and
      minocycline were prescribed as SAT in 72 (92%) and 6 (8%) patients, respectively.
      Adverse events were reported in 14 patients (18%), leading to SAT discontinuation
      in 6 of them (8%). After a mean follow-up of 1020 +/- 597 days, a total of 22
      (28.2%) patients had failed including 3 cases (3.8%) with documented acquisition
      of tetracycline resistance in initial pathogen(s). CONCLUSIONS: Our results
      suggest that oral cyclines used as SAT in patients treated for PJI have an
      acceptable tolerability and effectiveness and appear to be a reasonable option in
      this setting.

PMID- 29052798
TI  - Curcumin pretreatment prevents hydrogen peroxide-induced oxidative stress through
      enhanced mitochondrial function and deactivation of Akt/Erk signaling pathways in
      rat bone marrow mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (BMSCs)-based therapy has emerged as a
      desirable modality for the treatment of tissue injury with promising therapeutic
      effects; however, low survival rate of transplanted cells due to harsh
      microenvironment with hypoxia and oxidative stress results in hampered
      therapeutic benefits of this therapy. Curcumin, a natural bioactive product, is a
      dietary component which has gained increasing attention owing to its beneficial
      health properties. Here, we reported the protective effects of curcumin
      pretreatment on BMSCs injury induced by hydrogen peroxide (H2O2), which was used
      as ROS source of oxidative stress in vitro. We found that curcumin pretreatment
      remarkably inhibited H2O2-induced cell viability reduction, LDH leakage, and cell
      apoptosis in BMSCs. Moreover, curcumin pretreatment prevented H2O2-induced
      mitochondrial dysfunction via suppressing adenosine triphosphate loss, reactive
      oxygen species accumulation, and membrane potential decline. In addition,
      curcumin pretreatment markedly reduced the phosphorylation levels of Akt and
      Erk1/2. Taken together, our investigations demonstrated that curcumin
      pretreatment conferred BMSCs the ability to survive from H2O2-induced oxidative
      stress, which might attribute to its prevention of mitochondrial dysfunction and
      deactivation of Akt and Erk1/2 signaling pathways. Thus, this study sheds more
      light on the pharmacological mechanisms of curcumin, and suggests that BMSCs
      preconditioned with curcumin might be an effective way for cell therapy in tissue
      repair treatment.

PMID- 29052799
TI  - Treatment and outcome of subdural hematoma in patients with spontaneous
      intracranial hypotension: a report of 35 cases.
AB  - Spontaneous intracranial hypotension (SIH) is characterized by orthostatic
      headache, low CSF pressure and diffuse pachymeningeal enhancement on brain MRI.
      SIH results from spontaneous CSF leakage leading to brain sag. Sometimes, tearing
      of bridging veins may produce subdural hematomas (SDHs). Patients with SDH were
      identified retrospectively from 212 consecutive SIH patients. Data were collected
      on demographics, clinical courses, neuroimaging findings, treatment and outcome
      of SDH. Thirty-five patients (16%), (6 women, 29 men; aged 33-68; mean, 50 years)
      with SDH were recruited. They were divided into two groups: initially withSIH
      diagnosed (n = 29) and undiagnosed (n = 6). After conservative treatment, the
      first group underwent a lumbar epidural blood patch (EBP) (n = 27) and emergent
      evacuation of symptomatic SDH (n = 2). After EBP, ten patients had enlarged SDH.
      Nine of them underwent evacuation of symptomatic SDH with mass effect (ME). In
      the second group, three patients with clinical worsening from SIH underwent,
      erroneously, evacuation of mild SDH. They worsened after the evacuation; after
      SIH diagnosis was made, they underwent one EBP (n = 2) and three EBPs (the
      patient with coma). The other three cases with symptomatic SDH with ME underwent
      evacuation with recurrence of SDH (n = 2). All 35 patients enjoyed a good
      outcome. If conservative treatment is insufficient, EBP should be performed prior
      to hematoma irrigation. When an emergent evacuation is necessary before EBP, it
      is preferable to perform, after surgery, one early EBP before the patient gets up
      to prevent frequent recurrences of SDH by underlying CSF leakage.

PMID- 29052800
TI  - Dermatologist and Patient Preferences in Choosing Treatments for Moderate to
      Severe Psoriasis.
AB  - INTRODUCTION: The objective of the study was to determine the relative importance
      (RI) of treatment attributes psoriasis patients and physicians consider when
      choosing between biologic therapies based on psoriasis severity. METHODS: A
      discrete choice experiment (DCE) weighting preference for eight sets of
      hypothetical treatments for moderate or severe psoriasis was conducted. DCE
      hypothetical treatments were defined and varied on combinations of efficacy,
      safety, and dosing attributes [frequency/setting/route of administration (ROA)].
      RESULTS: When assuming moderate psoriasis in the patient DCE, ROA (RI 29%) and
      efficacy (RI 27%) drive treatment choices. When assuming severe disease in the
      DCE, patients preferred treatments with higher efficacy (RI 36%); ROA was
      relatively less important (RI 15%). From the physician perspective, ROA (RI 32%)
      and efficacy (RI 26%) were most important for moderate psoriasis patients. In the
      physician model for severe psoriasis, efficacy (RI 42%) was the predominant
      driver followed by ROA (RI 22%). Regardless of severity, probability of loss of
      response within 1 year was the least important factor. CONCLUSIONS: The severity
      of disease is a critical element in psoriasis treatment selection. There are high
      levels of alignment between physician- and patient-derived preferences in
      biologic treatment choice selection for psoriasis. FUNDING: Janssen
      Pharmaceuticals.

PMID- 29052801
TI  - Coronary flow response to remote ischemic preconditioning is preserved in old
      cardiac patients.
AB  - BACKGROUND: The effect of remote ischemic preconditioning (RIPC) on coronary flow
      in elderly cardiac patients has not been investigated yet. Thus, we aimed to
      study the change of coronary flow subsequent to RIPC in old patients with heart
      diseases and to identify its main correlates. METHODS: Ninety-five elderly
      patients (aged >= 65 years) accessing cardiac rehabilitation ward underwent
      transthoracic ultrasound evaluation of peak diastolic flow velocity of left
      anterior descending artery. Measurements of coronary flow velocity were performed
      on baseline and after an RIPC protocol (three cycles of 5 min ischemia of right
      arm alternating 5 min reperfusion). Differences between subjects with coronary
      flow velocity change over or equal the 75 degrees  percentile (high-responders)
      and subjects with a coronary flow velocity change under the 75 degrees 
      percentile (low-responders) were assessed. RESULTS: In enrolled elderly heart
      patients, coronary flow velocity significantly augmented from baseline after RIPC
      [0.23 m/s (0.18-0.28) vs 0.27 m/s (0.22-0.36); p < 0.001 by Wilcoxon test]. High
      responders to RIPC were significantly younger and in better functional status
      than low-responders. Heart failure resulted as the main variable associated with
      impairment of RIPC responsiveness (R 2 = 0.202; p = 0.002)]. CONCLUSIONS: Our
      sample of old cardiac patients presented a significant median increment of
      coronary flow velocity after RIPC. The magnitude of the observed change of
      coronary flow velocity was comparable to that previously described in healthy
      subjects. The coronary response to RIPC was attenuated by heart failure. Further
      research should define whether such RIPC responsiveness is associated with
      cardioprotection and carries prognostic implications.

PMID- 29052803
TI  - Clinical guidelines for the prevention and treatment of osteoporosis from the
      Italian Society for Orthopaedics and Traumatology: preface.

PMID- 29052802
TI  - The development of episodic future thinking in middle childhood.
AB  - The ability to imagine future events (episodic future thinking-EFT) emerges in
      preschoolers and further improves during middle childhood and adolescence. In the
      present study, we focused on the possible cognitive factors that affect EFT and
      its development. We assessed the ability to mentally project forward in time of a
      large cohort of 135 6- to 11-year-old children through a task with minimal
      narrative demands (the Picture Book Trip task adapted from Atance and Meltzoff in
      Cogn Dev 20(3):341-361. doi:10.1016/j.cogdev.2005.05.001, 2005) in order to avoid
      potential linguistic effects on children's performance. The results showed that
      this task can be used to assess the development of EFT at least until the age of
      8. Furthermore, EFT scores correlated with measures of phonological short-term
      and verbal working memory. These results support the possibility that cognitive
      factors such as working memory play a key role in EFT.

PMID- 29052804
TI  - Correction to: Effectiveness of Exercise Interventions to Improve Postural
      Control in Older Adults: A Systematic Review and Meta-Analyses of Centre of
      Pressure Measurements.
AB  - Page 103, Table 1: The cell entry in the 'Terms used' column which previously
      read: "Centre of pressure OR center of pressure OR COP OR postural sway OR
      postural stability OR postural control OR balance OR force plat*".

PMID- 29052805
TI  - Sublingual Buprenorphine Efficacy in Renal Colic Pain Relief: A Randomized
      Placebo-Controlled Clinical Trial.
AB  - INTRODUCTION: This study was designed to compare the analgesic efficacy of
      sublingual (SL) buprenorphine and intravenous (IV) ketorolac for renal colic pain
      relief. METHODS: The present study was carried out as a double-blind, double
      dummy randomized clinical trial in patients diagnosed with acute renal colic
      attending the emergency department. The study subjects were 63 patients with
      confirmed renal stones. The subjects were randomly divided into two groups. One
      group, which included 32 patients, received SL buprenorphine tablets (2 mg) with
      an IV placebo, and another group, including 31 patients, received ketorolac
      tromethamine (30 mg) with a SL placebo. After medication, the pain of subjects
      was measured by a standard visual pain analogous scale (VPAS) in minutes 0, 20,
      40, and 60 of study. Also, probable adverse effects were recorded. RESULTS: In
      28.1% of patients in the buprenorphine group, the mean pain score decreased from
      9.2 to 5.9, 2.8, and 1.5 after 20, 40, and 60 min, respectively, as determined by
      VPAS. Also, in 38.7% of patients in the ketorolac group, the mean pain score
      decreased from 9.1 to 5.5, 3.0, and 1.6 after 20, 40, and 60 min, respectively,
      as determined by VPAS. The two groups did not significantly differ for pain
      reduction at 20, 40, and 60 min (P value = 0.16, 0.34, and 0.3, respectively). No
      adverse effects were seen in the ketorolac group, but vomiting (18.8%), nausea
      (18.8%), and dizziness (21.9%) were detected in the buprenorphine group.
      CONCLUSIONS: We found no difference between SL buprenorphine and intravenous
      ketorolac in renal colic pain relief but more adverse effects in the
      buprenorphine group. Trial Registration Iranian Registry of Clinical trials
      identifier, IRCT2015041421773N1.

PMID- 29052806
TI  - Profiling Autism Symptomatology: An Exploration of the Q-ASC Parental Report
      Scale in Capturing Sex Differences in Autism.
AB  - The Questionnaire for Autism Spectrum Conditions (Q-ASC) was developed by Attwood
      et al. (2011) to identify gender-sensitive profiles of autism symptomatology;
      prioritise and adjust the direction of clinical interventions; and support
      positive psychosocial outcomes and prognosis into adulthood. The current research
      piloted the Q-ASC with parents of 238 children with a clinical diagnosis of ASD
      Level 1 (without intellectual or language impairment). Data analysis revealed
      eight interpretable and reliable components of the Q-ASC using Principle
      components analysis. Comparisons across age and gender groups found statistically
      significant mean differences of parent-reported characteristics. The findings
      from this study aim to identify improvements in the Q-ASC towards the future
      assessment of the sensitivity and diversity of presentations of autism among
      female children and adolescents.

PMID- 29052809
TI  - The contribution of mutations in MYH7 to the onset of cardiomyopathy.

PMID- 29052808
TI  - Signs for secondary buildup of heavy metals in soils at the periphery of Athens
      International Airport, Greece.
AB  - Emissions from civil airports are similar to those observed in industrial and
      urban areas. While air pollution and noise levels are regularly monitored and
      assessed, information on the status of heavy metals in soils close to airport
      facilities is limited. In this study, we monitored and assessed heavy metal
      distribution in soils close to Athens International Airport (AIA) in Attica,
      Greece. Following a grid sampling scenario, topsoil samples were collected from
      86 sites at the periphery of AIA and total and available forms of Cu, Zn, Fe, Mn,
      Ni, Cr, Pb, and Ba concentrations were determined in aqua regia and DTPA soil
      extracts, respectively. Median concentration values for both metal forms are not
      considered as particularly high. However, 90th percentile concentration values
      for some metals are high, indicating soil enrichment. Evaluation of enrichment
      factor (EF) and availability ratio (AR) values and EFs spatial distribution have
      led to consistent conclusions of secondary and ongoing metal accumulation in the
      soils of the studied area. Tessier sequential extraction procedure was applied to
      10% of the soil samples and the results showed high potential availability of Pb,
      Mn, Cu, and Ni, further supporting the continuous metal accumulation in the
      studied soils.

PMID- 29052807
TI  - Current trends in mouse models of glioblastoma.
AB  - Glioblastoma is the most deadly brain tumor type and is characterized by a severe
      and high rate of angiogenesis, remaining an incurable disease in the majority of
      cases. Mechanistic understanding of glioblastoma initiation and progression is
      complicated by the complexity of genetic and/or environmental initiating events
      and lack of clarity regarding the cell or tissue of origin. To determine these
      mechanisms, mouse models that recapitulate the molecular and histological
      characteristics of glioblastoma are required. Unlike in other malignancies, viral
      mediated mouse models of glioblastoma rather than chemically induced mouse models
      have been developed because of its sensitivity to viruses. Based on recent
      molecular analyses reported for human glioblastoma, this review critically
      evaluates genetically engineered, xenograft, allograft, viral-mediated, and
      chemically induced mouse models of glioblastoma. Further, we focus on the
      clinical value of these models by examining their contributions to studies of
      glioblastoma prevention, tumorigenesis, and chemoresistance.

PMID- 29052810
TI  - Projecting the Supply and Demand for Certified Genetic Counselors: a Workforce
      Study.
AB  - As of May 2017, there were 4242 Certified Genetic Counselors (CGC) (American
      Board of Genetic Counseling, Inc. 2017) and 41 graduate-level genetic counseling
      training programs (Accreditation Council for Genetic Counseling 2017) in North
      America, and the demand for CGCs continues to increase. In the Fall of 2015 the
      Genetic Counselor Workforce Working Group, comprised of representatives from the
      American Board of Genetic Counseling (ABGC), the Accreditation Council for
      Genetic Counseling (ACGC), the Association of Genetic Counseling Program
      Directors (AGCPD), the American Society of Human Genetics (ASHG), and the
      National Society of Genetic Counselors (NSGC) commissioned a formal workforce
      study to project supply of and demand for CGCs through 2026. The data indicate a
      shortage of genetic counselors engaged in direct patient care. Assuming two
      scenarios for demand, supply is expected to reach equilibrium between 2024 and
      2030. However, given the rate of growth in genetic counseling training programs
      in the six months since the study was completed, it is reasonable to expect that
      the number of new programs may be higher than anticipated by 2026. If true, and
      assuming that growth in programs is matched by equivalent growth in clinical
      training slots, the supply of CGCs in direct patient care would meet demand
      earlier than these models predict.

PMID- 29052811
TI  - Four Saccharomyces species differ in their tolerance to various stresses though
      they have similar basic physiological parameters.
AB  - Saccharomyces species, which are mostly used in the food and beverage industries,
      are known to differ in their fermentation efficiency and tolerance of adverse
      fermentation conditions. However, the basis of their difference has not been
      fully elucidated, although their genomes have been sequenced and analyzed. Five
      strains of four Saccharomyces species (S. cerevisiae, S. kudriavzevii, S.
      bayanus, and S. paradoxus), when grown in parallel in laboratory conditions,
      exhibit very similar basic physiological parameters such as membrane potential,
      intracellular pH, and the degree to which they are able to quickly activate their
      Pma1 H+-ATPase upon glucose addition. On the other hand, they differ in their
      ability to proliferate in media with a very low concentration of potassium, in
      their osmotolerance and tolerance to toxic cations and cationic drugs in a growth
      medium specific manner, and in their capacity to survive anhydrobiosis. Overall,
      S. cerevisiae (T73 more than FL100) and S. paradoxus are the most robust, and S.
      kudriavzevii the most sensitive species. Our results suggest that the difference
      in stress survival is based on their ability to quickly accommodate their cell
      size and metabolism to changing environmental conditions and to adjust their
      portfolio of available detoxifying transporters.

PMID- 29052812
TI  - Fumarase Deficiency: A Safe and Potentially Disease Modifying Effect of High
      Fat/Low Carbohydrate Diet.
AB  - Fumarate hydratase deficiency (FHD) caused by biallelic alterations of the FH
      (fumarate hydratase) gene is a rare disorder of the tricarboxylic acid cycle,
      classically characterized by encephalopathy, profound psychomotor retardation,
      seizures, a spectrum of brain abnormalities and early death in childhood. Less
      common milder phenotypes with moderate cognitive impairment and long-term
      survival have been reported. In addition, heterozygous mutations of the FH gene
      are responsible for hereditary leiomyomatosis and renal cell cancer (HLRCC).
      There is currently no recommended disease modifying treatment for FHD and only
      isolated reports of unsuccessful dietary modifications. Herein, we describe the
      safe and possibly disease modifying effect of a high fat, low carbohydrate diet
      in a 14-year-old female with severe FHD.

PMID- 29052813
TI  - Exploration for reliable radiographic assessment method for hinge-like
      hypermobility at atlanto-occipital joint.
AB  - PURPOSE: Hinge-like hyper-mobility is occasionally observed at the atlanto
      occipital (O-C1) joint. However, it has not been clear if this kind of hinge-like
      hyper-mobility at the O-C1 joint should be regarded as "pathologic", or referred
      to as "instability". To solve this issue, we aimed to establish a reliable
      radiographic assessment method for this specific type of O-C1 instability and
      figure out the "standard value" for the range of motion (ROM) of the O-C1 joint.
      METHODS: To figure out the standard range of the O-C1 angle, we acquired magnetic
      resonance imaging (MRI) sagittal views of the cervical spine for 157 healthy
      volunteers [average: 37.4 year-old (yo)] without spine diseases, at neutral,
      maximum flexion and maximum extension positions. RESULTS: The average value (AVE)
      for ROM of O-C1 angle was 9.91 degrees . The standard value for ROM of O-C1 angle
      was calculated as 0 degrees -21 degrees . There was no statistically significant
      gender difference. We also found that the older population (? 40 yo)
      significantly had a larger ROM of O-C1 angle (AVE: 11.72 degrees ) compared to
      the younger population (< 40 yo) (AVE: 8.99 degrees ). CONCLUSIONS: We consider
      that hinge-like instability at O-C1 joint, which cannot be assessed by measuring
      Powers ratio, can be assessed by measuring the range of O-C1 angles using dynamic
      MRI. Evaluation of O-C1 instability is important especially when we perform
      surgical treatment for diseases with upper cervical instability (such as retro
      odontoid pseudotumor). We consider that the current study provides important
      information in such a case.

PMID- 29052814
TI  - Responsiveness and minimal important change of the NeckPix(c) in subjects with
      chronic neck pain undergoing rehabilitation.
AB  - PURPOSE: The NeckPix(c) is a simple and rapid means of measuring the beliefs of
      subjects with chronic neck pain concerning pain-related fears of a specific set
      of activities of daily living. The original version showed satisfactory
      psychometric properties. This observational study is aimed at evaluating its
      responsiveness and minimal important changes (MICs) in subjects with chronic neck
      pain. METHODS: At the beginning, at the end of an 8-week rehabilitation programme
      as well as at the one-year follow-up, 153 subjects completed the NeckPix(c).
      After the programme and at follow-up, subjects and physiotherapists also
      completed the global perceived effect (GPE) scale, which was divided to produce a
      dichotomous outcome. Responsiveness was calculated by distribution [effect size
      (ES); standardised response mean (SRM)] and anchor-based methods [receiver
      operating characteristics (ROC) curves; correlations between change scores of the
      NeckPix(c) and GPEs]. ROC curves were also used to compute MICs. RESULTS: The ES
      ranged from 0.95 to 1.26 and the SRM from 0.84 to 0.98 at post-treatment and
      follow-up based on subjects' and physiotherapists' perspective. The ROC analyses
      revealed AUCs of 0.89 and 0.97 at post-treatment and follow-up, respectively;
      MICs (sensitivity; specificity) were of 6 (0.82; 0.88) and 8 (0.80; 0.92) at post
      treatment and of 8 (0.95; 0.90 based on subjects and 0.95; 0.92 based on
      physiotherapists perspective) at follow-up. The correlations between change
      scores of the NeckPix(c) and GPEs ranged from -0.69 to -0.82. CONCLUSIONS: The
      NeckPix(c) was sensitive in detecting clinical changes in subjects with chronic
      neck pain undergoing rehabilitation. We recommend taking the MICs provided into
      account when assessing subjects' improvement or planning studies in this clinical
      context.

PMID- 29052815
TI  - Letter to the editor concerning "Do we have the right PROMs for measuring
      outcomes in lumbar spinal surgery?" by O.M. Stokes et al. Eur Spine J (2017)
      26:816-824.

PMID- 29052816
TI  - Depressive Symptoms Predict Anti-tumor Necrosis Factor Therapy Noncompliance in
      Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy
      in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a
      factor in medication failure. Few studies have evaluated the contribution of
      depressive symptoms to medication noncompliance in anti-TNF therapies. METHODS: A
      retrospective chart review was performed in a single-center tertiary care IBD
      center for patients with Crohn's disease and ulcerative colitis starting anti-TNF
      therapy over a 2-year period. Medication noncompliance was defined as
      interruption of medication (not filling anti-TNF prescription if injectable or
      not getting infliximab infusion for 30 days beyond needed date for continuation)
      due to patient-driven circumstances. Depressive symptoms were evaluated at
      baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with
      PHQ-9 >= 10 indicative of at least moderate depressive symptoms. Statistical
      analysis was performed using Cox proportional hazards regression controlling for
      age, sex, psychiatric history, and disease. RESULTS: A total of 246 patients (75
      with ulcerative colitis, 171 with Crohn's disease) were started on anti-TNF
      therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported
      in the medical record. Thirty-three patients (13%) were noncompliant in follow
      up. Sixty patients (24%) had at least moderate depressive symptoms at baseline
      (PHQ >= 10). Depressive symptoms at baseline were significantly associated with
      noncompliance in follow-up (hazards ratio 2.28, CI 1.1-4.6, p < 0.05).
      CONCLUSION: Depressive symptoms at baseline were associated with medication
      noncompliance of anti-TNF therapies at follow-up when controlling for age, sex,
      disease type, and history of psychiatric disease.

PMID- 29052817
TI  - Androgen Signaling in Esophageal Adenocarcinoma Cell Lines In Vitro.
AB  - BACKGROUND: We showed previously that nuclear localization of the androgen
      receptor (AR) and expression of the androgen-responsive gene FK506-binding
      protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with
      decreased patient survival, suggesting a role for androgens in this cancer. AIM:
      To investigate the effect of the AR ligand 5alpha-dihydrotestosterone (DHT) on AR
      expressing EAC cell lines in vitro. METHODS AND RESULTS: In tissue resection
      specimens from EAC patients, FKBP5 expression was positively associated with
      proliferation as measured by Ki-67 expression. We stably transduced AR into three
      AR-negative EAC cell lines, OE33, JH-EsoAd1, and OE19, to investigate androgen
      signaling in vitro. In the AR-expressing cell lines, 10 nM DHT, the concentration
      typically used to study AR signaling, induced changes in the expression of
      androgen-responsive genes and inhibited proliferation by inducing cell cycle
      arrest and senescence. At lower DHT concentrations near the half maximal
      inhibitory concentration (IC50), the AR-expressing cell lines proliferated and
      there were changes in the expression of androgen-responsive genes. In direct co
      culture with cancer-associated fibroblast-like PShTert myofibroblasts, 10 nM DHT
      induced changes in the expression of androgen-responsive genes but did not
      inhibit proliferation. CONCLUSIONS: This is the first study to show that EAC cell
      lines respond to androgen in vitro. Proliferation together with the expression of
      androgen-responsive genes was dependent on the concentration of DHT, or the
      presence of a permissive microenvironment, consistent with observations in the
      tissues. These findings are consistent with a role for androgen signaling in EAC.

PMID- 29052818
TI  - Out-of-Pocket Cost Is a Barrier to Therapeutic Drug Monitoring in Inflammatory
      Bowel Disease.
AB  - BACKGROUND: Therapeutic drug monitoring (TDM) is increasingly performed to
      optimize biologic therapy in inflammatory bowel disease (IBD). However, patients
      and physicians may be reluctant to perform TDM due to concerns related to
      potential out-of-pocket costs. AIMS: The aim of this study was to evaluate
      patient understanding and attitudes toward TDM in different clinical scenarios
      with and without potential out-of-pocket costs. METHODS: Adult IBD patients at a
      tertiary gastroenterology clinic were anonymously surveyed from March to
      September 2016 to assess their understanding of and willingness to undergo TDM in
      a variety of clinical scenarios, both with and without a potential out-of-pocket
      cost. Responses were analyzed for associations with changes in attitudes if out
      of-pocket costs were involved. RESULTS: Of 118 completed surveys, 68.2% of
      patients were aware of or had previously undergone TDM. Patient willingness to
      undergo TDM was high both with and without potential out-of-pocket costs (70 and
      98%, respectively); however, patients were significantly less willing with out-of
      pocket cost (p < 0.01). Higher disease-related quality of life scores, as
      measured by the short inflammatory bowel disease questionnaire (SIBDQ), was
      significantly associated with an increased willingness to assume a potential out
      of-pocket cost (p = 0.007). CONCLUSIONS: Overall, patients understand and are
      willing to undergo TDM in certain potentially beneficial clinical scenarios,
      however, are significantly less willing if paying out-of-pocket. A higher SIBDQ
      score was associated with an increase in willingness to undergo TDM when out-of
      pocket cost was involved. Physicians should discuss TDM with their patients in
      order to make an informed and personalized treatment decision.

PMID- 29052819
TI  - Getting a Low Grade for Missing High-Grade Dysplasia and Colorectal Cancer in
      IBD.

PMID- 29052820
TI  - Evaluation of different treatment protocols for combined injury-induced lung
      injury in rabbits.
AB  - BACKGROUND: This study aims to evaluate the effectiveness of different treatment
      regimens on combined injury-induced lung injury. METHODS: Rabbits were subjected
      to non-lethal closed-chest bilateral lung contusion followed by a 30% total body
      surface area scald burn. The rabbits were randomly assigned to resuscitation
      groups that maintained a minimum mean arterial blood pressure of 70 mmHg using
      one of the following three methods: normal saline plus polygeline injection in a
      ratio of 1:1 (1:1G), normal saline plus polygeline injection in a ratio of 1:2
      (1:2G), and normal saline plus polygeline injection in a ratio of 1:3 (1:3G),
      After injury, lung injury was assessed using lung wet-to-dry (W/D) weight ratio,
      enzyme-linked immunosorbent assay, and real-time PCR. RESULTS: In the 1:3 fluid
      resuscitation group, rabbits exhibited significantly reduced lung W/D ratio,
      alveolar hemorrhage, myeloperoxidase activity, and IL-8 and TNF-alpha levels in
      the serum compared with the 1:1 or 1:2 fluid resuscitation groups. The 1:3 fluid
      resuscitation-treated rabbits also attenuated ultrastructural changes in the lung
      24 h after the combined injury. CONCLUSION: This study demonstrated the impact of
      fluid resuscitation on combined injury-induced lung injury. Further, 1:3 fluid
      resuscitation treatment at the early stage of lung injury after combined lung
      contusion and burn injury was found to be more effective.

PMID- 29052821
TI  - Evaluation of the systemic antiinflammatory effects of levosimendan in an
      experimental blunt thoracic trauma model.
AB  - BACKGROUND: Blunt thoracic injury often leads to pulmonary contusion and the
      development of acute respiratory distress syndrome, which carries a high risk of
      morbidity and mortality, originating from the local and systemic inflammatory
      states. This study aimed to investigate the local and systemic antiinflammatory
      effects of levosimendan in rat models of blunt chest trauma. METHODS: A total of
      32 Wistar albino rats were randomly assigned to one of the following four groups:
      control, sham, low-dose levosimendan (LDL) (5 ug/kg loading dose for 10 min and
      0.05 ug/kg/min intravenous infusion), and high-dose levosimendan (HDL) (10 ug/kg
      loading dose for 10 min and 0.1 ug/kg/min intravenous infusion). Blunt chest
      trauma was induced, and after 6 h, the contused pulmonary tissues were
      histopathologically and immunohistopathologically evaluated, serum TNF-alpha, IL
      1beta, IL-6, and NO levels were biochemically evaluated. RESULTS: The mean
      arterial pressure was low throughout the experiment in the LDL and HDL groups,
      with no statistically difference between the groups. Levosimendan reduced the
      alveolar congestion and hemorrhage, which developed after inducing trauma.
      Neutrophil infiltration to the damaged pulmonary tissue was also reduced in both
      the LDL and HDL groups. In rats in which pulmonary contusion (PC) was observed,
      increased activation of nuclear factor kappa B was observed in the pulmonary
      tissue, and levosimendan did not reduce this activation. Both high and low doses
      of levosimendan reduced serum IL-1beta levels, and high doses of levosimendan
      reduced IL-6 and NO levels. TNF-alpha levels were not reduced. CONCLUSION: In
      conclusion, the results showed that in a rat model of PC, the experimental agent
      levosimendan could reduce neutrophil cell infiltration to damaged pulmonary
      tissues and the systemic expressions of some cytokines (IL-1beta, IL-6, and NO),
      thereby partially reducing and/or correcting pulmonary damage. Systemic
      inflammatory response that occurs after trauma could also be reduced.

PMID- 29052823
TI  - Can we predict mortality in patients with necrotizing fasciitis using
      conventional scoring systems?
AB  - BACKGROUND: This study compared the predictive accuracy of four scoring systems,
      namely Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential
      Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II),
      and Mortality in Emergency Department (MEDS), for estimating prognosis in
      patients with necrotizing fasciitis. METHODS: Seventy-four patients who presented
      with necrotizing fasciitis were retrospectively examined. The ability of the
      scoring systems to predict mortality was assessed by comparing the estimated
      mortality rates in mortality groups (survivors/non-survivors), and mortality
      rates among survivors and non-survivors with an estimated mortality of >10%, 30%,
      and 50% in the scoring systems were compared in pairs. RESULTS: Estimated
      mortality rates in the survivor and non-survivor groups were different for all
      the scoring systems. The estimated mortality rates of APACHE II and SAPS II were
      much closer to the actual mortality rates than the other two scoring systems.
      When the predicted mortality rates were analyzed as limits for a mortality risk,
      the predicted mortality rate by APACHE II was superior to that by SAPS II.
      CONCLUSION: The studied scoring systems had significantly higher predicted
      mortality rates in non-survivors than in survivors; however, they all
      underestimated the mortality rate. APACHE II and SAPS II were relatively superior
      for estimating mortality in patients with necrotizing fasciitis. APACHE II rather
      than the other scoring systems should be currently used.

PMID- 29052822
TI  - Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal
      adhesion prevention.
AB  - BACKGROUND: In our present study, we aimed to evaluate the effects of
      taurolidine, a blocking agent of fibrin deposition, and icodextrin, a colloid
      osmotic material that also inhibits fibrin accumulation, and the effect of their
      application separately and concomittantly in intra-abdominal adhesion prevention.
      METHODS: Forty BALB/c male mice, weighing 30-35 g and 11-12 weeks old were
      divided into four groups as follows: group 1: control group, group 2: taurolidine
      group, group 3: icodextrin group, and group 4: taurolidine and icodextrin group.
      Animals were sacrificed by cervical dislocation after 14 days. The adhesions were
      classified and scored by two blinded researchers according to Nair's macroscopic
      adhesion staging system and microscopically evaluated using Zuhlke classification
      system. RESULTS: In group 2 there was no mice with score 4. In group 3, scores 3
      and 4 were absent. Scores 2, 3, and 4 were not detected in group 4. The mean
      value of adhesion scores decreased from groups 1 to 4. There was a significant
      statistical difference between all the groups and group 1. There was no change
      between the study groups on macroscopic examination, whereas histopathological
      examination revealed statistically significance between group 4 and other groups.
      CONCLUSION: Taurolidine and icodextrin, when used alone or together, decrease
      postoperative intra-abdominal adhesion formation. Macroscopic appearence was not
      supportive of statistical difference between group 4 and other groups.
      Microscopic evaluation paves the road for future studies for determining
      significance when taurolidine and icodextrin are applied concomittantly.
      Additional experimental studies are required for dose adjustment.

PMID- 29052824
TI  - Usefulness of FGSI and UFGSI scoring systems for predicting mortality in patients
      with Fournier's gangrene: A multicenter study.
AB  - BACKGROUND: This study aimed to evaluate the usefulness of Fournier's gangrene
      scoring index (FGSI) and Uludag FGSI (UFGSI) for predicting mortality in patients
      with FG. METHODS: Patients who underwent treatment and follow-up in the A
      division department of general surgery at two education and research hospitals
      between January 2012 and December 2015 were evaluated for mortality-related
      factors. The sensitivities of FGSI and UFGSI scoring systems for predicting
      mortality-related factors and disease prognosis were evaluated. Patients were
      grouped as survivors (Group I) or non-survivors (Group II). RESULTS: In total, 29
      patients were included in the study. The mean age (+/-SD) was 51.52+/-13.36
      years. The mortality rate was 20.6% (six patients). Bacterial growth was observed
      in wound cultures of 17 patients (58.6%). Of the patients with bacterial growth,
      11 (47.8%) were in Group I and six (100%) were in Group II. The presence of
      bacterial growth was significantly associated with mortality (p=0.028). Fourteen
      patients (48.3%) had comorbid conditions. The number of comorbid conditions was
      related (p=0.049). FGSI and UFGSI scores were significantly higher in Group II
      than in Group I (p=0.002 and p=0.001, respectively). Among UFGSI parameters,
      extent of disease, body temperature, pulse rate, and HCO3 values were
      significantly higher in Group II than in Group I (p<0.05). The FGSI and UFGSI
      scoring systems had 100% sensitivity and 78.2% and 73.9% specificity,
      respectively, for predicting mortality. CONCLUSION: The FGSI and UFGSI scoring
      systems are valuable for predicting mortality in patients with FG. The extent of
      the disease was an important prognostic parameter in this study. Whichever
      scoring system is used, we suggest the use of the extent of disease score in
      UFGSI.

PMID- 29052825
TI  - Managing endoscopic retrograde cholangiopancreatography-related complications in
      patients referred to the surgical emergency unit.
AB  - BACKGROUND: The goal of this study was to present our experience in the
      management of endoscopic retrograde cholangiopancreatography-related
      complications in patients referred to our surgical emergency unit by various
      endoscopy centers. METHODS: A retrospective investigation was conducted on the
      records of the 54 patients who were referred to our surgical emergency unit
      between October 2005 and January 2014 due to endoscopic retrograde
      cholangiopancreatography-related complications. RESULTS: There were 25 and 29
      female and male patients, respectively. Pancreatitis was the most common
      complication (38.8%). Perforation (27.7%), infection (20.3%), and bleeding
      (12.9%) were the other complications. In 22.2% of cases, patients were died. The
      mortality rate was the highest in patients with perforation (40%). The mean age
      of the patients who were died due to complications was 75.9 years (range, 47-94
      years). In total, 41.6% of the patients were died within the first week and 33.3%
      were died within the second week following ERCP. Nearly half of these patients
      had a cancerous disease (one had metastatic breast cancer, one had a gallbladder
      cancer, one had a duodenal cancer, and the other three had periampullary cancers)
      and 50% of the patients who died also had cardiopulmonary and/or cerebrovascular
      disorders. CONCLUSION: Comprehending and managing the main risk factors can
      minimize complications; however, they would not be eliminated. Moderate and
      severe complications may increase the mortality rates, particularly in high-risk
      patients.

PMID- 29052826
TI  - Fournier's gangrene: A retrospective analysis of 25 patients.
AB  - BACKGROUND: Fournier's gangrene is a surgical emergency that progresses rapidly
      and insidiously and results in high morbidity and mortality rates unless it is
      immediately diagnosed and managed. Here we analyze the outcomes of patients who
      were followed up and treated for Fournier's gangrene. METHODS: We conducted a
      retrospective analysis of the medical data of 25 patients operated on for
      Fournier's gangrene between January 2010 and June 2015. The diagnosis of
      Fournier's gangrene was made by performing a physical examination. Patients who
      had genital, perineal, and perianal tenderness; induration; cyanosis; gangrene;
      and subcutaneous crepitation were considered as having Fournier's gangrene.
      Following resuscitation, aggressive surgical debridement was performed and vacuum
      assisted closure (VAC) was conducted in addition to debridement in select
      patient. Repeat debridements were performed as requirement. RESULTS: This study
      included 25 patients. Fourteen patients (56%) were females and 11 (44%) were
      males. The mean age of the patients was 54.3 years (range: 27-82 years). The mean
      duration of hospital stay was 21.4 days; the mean number of debridements
      performed was 2.4. Thirteen patients (52%) had perianal abscesses, and 20 (80%)
      had diabetes mellitus. All patients underwent extensive debridement; 16 patients
      (64%) underwent VAC in addition to debridement. Patients undergoing VAC had
      significantly longer durations of hospital stay and a higher mean number of
      debridements performed (p=0.004 and p=0.048, respectively). An ostomy was made in
      one patient, and one patient died. CONCLUSION: In Fournier's gangrene, early
      diagnosis, effective resuscitation, aggressive debridement, and VAC application
      in suitable cases may reduce the morbidity and mortality rates and the need for
      an ostomy.

PMID- 29052827
TI  - Primary exploration for radial nerve palsy associated with unstable closed
      humeral shaft fracture.
AB  - BACKGROUND: The treatment of radial nerve palsy caused by closed humeral shaft
      fracture is a matter of debate. The purpose of this study is to evaluate the
      outcome of early surgical management of radial nerve palsy in patients with
      unstable closed humeral shaft fractures and to determine whether patients with
      this injury should be surgically explored. METHODS: Medical records of 15
      consecutive patients who had undergone open reduction and internal fixation for
      unstable closed humeral shaft fractures were reviewed. Injury mechanisms,
      radiographs, intraoperative findings of the injured nerve, and clinical
      improvement were analyzed. Of the 15 patients, two were injured during simple
      falls, two during baseball pitching, one by a fall from a height, one during
      skiing, and one by direct machine impaction during work. Fracture locations were
      middle humerus in six patients, middle-distal in eight patients, and middle
      proximal in one patient. Fracture patterns were transverse fracture in six
      patients, butterfly segment fracture in four patients, oblique segment fracture
      in three patients, and spiral fracture in two patients. RESULTS: Eleven patients
      showed macroscopically intact nerves, and four had total nerve transection. All
      four patients with total nerve transection were injured in traffic accident. Of
      these four patients, one showed comminuted fracture with butterfly fragment on
      the middle-distal shaft and the other three showed displaced transverse fracture
      on the middle to middle-distal shaft area. Transected nerves were directly
      repaired in two patients. In the other two patients, humerus shortening and nerve
      grafting were performed because of mangled nerve endings. All patients who had
      intact nerves showed fully recovered function at the last follow-up. CONCLUSION:
      For radial nerve palsy accompanied by unstable humeral shaft fracture, primary
      exploration of the radial nerve and open reduction and plate fixation of the
      fracture should be considered as a treatment of choice. High-energy trauma,
      fracture location at the middle-distal humerus, and simple transverse fracture or
      comminuted fracture with butterfly fragment seems to be risk factors for radial
      nerve transection.

PMID- 29052828
TI  - Long-term results of primary repair of combined cuts on the median and ulnar
      nerves in the forearm.
AB  - BACKGROUND: The objective of this clinical study was to evaluate sensory and
      motor functions in the later period following primary repair of combined injuries
      of the ulnar and median nerves in the forearm at proximal, middle, and distal
      levels. METHODS: Later period sensory evaluation of ulnar and median combined
      cuts was performed using two-point discrimination and monofilament tests. On the
      other hand, motor evaluation was performed by determining dorsal palmar
      interosseus strength for the ulnar nerve and abductor pollicis brevis muscle
      strength for the median nerve. Cold intolerance, object recognition, and weight
      discrimination were also reviewed. RESULTS: In total, 26 patients with ulnar
      median combined cut and aged between 5 and 59 years were included in this study.
      Although no deficiency was observed in the sensory functions of any of the
      patients, a decrease in tactile sensation was detected in the median sensory
      region in 12 (46%) patients and in the ulnar sensory region in 7 (26%) patients.
      The most significant loss in terms of motor functions was detected in the
      opposition pinch strength. Two patients developed claw hand and two showed joint
      contracture. CONCLUSION: Ideal treatment for peripheral nerve injuries should be
      primary repair. Restoration of the motor function in the median nerve is
      relatively easier than that in the ulnar nerve. No significant difference was
      observed in terms of sensory function. An alternative is needed for primary
      repair because of lack of motor function in proximal ulnar incisions. There is no
      standardization of tests performed for peripheral nerve repair.

PMID- 29052829
TI  - ESIN and K-wire fixation have similar results in pediatric both-bone diaphyseal
      forearm fractures.
AB  - BACKGROUND: The purpose of this study was to compare short-term radiographic and
      clinical results of pediatric both-bone diaphyseal forearm fractures treated with
      intramedullary nail fixation using titanium nails or K-wires. METHODS: This was a
      prospective comparative trial. In total, 43 patients with both-bone open or
      closed forearm fractures who underwent surgical treatment with intramedullary
      fixation were randomly classified into two groups. Three patients did not return
      for the follow-up and were excluded from the study. Twenty of the 40 patients
      were assigned to the elastic stable intramedullary nail group and 20 were
      assigned to the K-wire group. Demographic data suggested no difference between
      the two groups except for the side of injury. Perioperative data and radiological
      and clinical outcomes were evaluated. RESULTS: The cohort comprised 5 girls and
      35 boys whose mean age was 11.60 +/- 2.69 years. Except the proportion of
      patients who were conservatively followed up preoperatively, all perioperative
      data were similar between the groups. Radiographic and functional results were
      similar. There were two delayed unions; one pin track infection and one re
      fracture. CONCLUSION: Intramedullary fixation of forearm fractures in children
      with titanium nail or K-wire does not affect radiological and clinical results.
      Both elastic stable intramedullary nail and K-wire fixation were effective in
      stabilizing pediatric diaphyseal forearm fractures.

PMID- 29052830
TI  - Diaphragmatic rupture: A single-institution experience and literature review.
AB  - BACKGROUND: Diaphragmatic rupture (DR) is a rare and potentially life-threatening
      event caused by trauma or spontaneously. DR occasionally occurs several months
      after the injury. Chest X-ray and computed tomography are the most effective
      diagnostic methods. Delay in DR diagnosis occurs frequently. This study aimed to
      examine and improve our understanding of the etiology, clinical presentation, and
      management of DR. METHODS: This study was performed at the Emergency and General
      Surgery Department of Fondazione I.R.R.C.S. Ca Granda, Ospedale Policlinico in
      Milan (Italy). Patients diagnosed with DR between 2001 and 2011 who underwent
      surgery were included, and their data were retrospectively collected. RESULTS:
      Fourteen patients were diagnosed with DR, mainly left-sided DR. Road traffic
      collisions were the main causes (86%). DR diagnosis was preoperatively
      established in eight patients (57%). Chest X-ray was diagnostic in 50% of the
      patients and computed tomography in three patients (60%). Twelve patients had a
      diaphragmatic hernia. DR was repaired with a mesh in two patients. Mean hospital
      stay was 16.6 days. CONCLUSION: Difficulty in achieving early diagnosis of DR is
      due to its nonspecific presentation. High index of suspicion is needed. Its
      treatment is using surgery involving reduction of the viscera and repair of the
      diaphragm defect.

PMID- 29052831
TI  - Klingsor syndrome: A rare surgical emergency.
AB  - Klingsor syndrome or self-Inflicted traumatic penile amputation is a rare
      clinical entity that is associated with psychiatric disorders, command
      hallucinations, religious preoccupations, substance abuse, and isolation from or
      neglect by society. In addition to being infrequently encountered, it is a rare
      surgical emergency, with paucity of data on appropriate and timely management to
      ensure optimal functional outcomes. We report the case of a 25-year-old unmarried
      male who inflicted this injury upon himself in a fit of paranoia as a way to
      expiate his sins and earn solace from God. An attempt at microvascular re
      implantation 12 h after the injury was successful, with adequate cosmetic and
      functional outcomes obtained. Thus, in this rare disease, despite a delay in
      presentation, a single attempt at re-implantation may still be worthwhile for
      obtaining optimal cosmetic and psychosocial benefits.

PMID- 29052832
TI  - Traumatic duodenal injury in children: A report of two cases.
AB  - Duodenal injury following blunt abdominal trauma in children is extremely rare.
      It commonly has a delayed presentation, thus leading to increased mortality and
      morbidity. We report two cases of isolated duodenal injury following blunt
      abdominal trauma in children.

PMID- 29052833
TI  - Emergency endovascular treatment of a ruptured external carotid artery
      pseudoaneurysm caused by a cervical stab wound: A case report and literature
      review.
AB  - The formation of external carotid artery (ECA) pseudoaneurysms caused by stab
      wounds is a rare vascular anomaly. Although the surgical exploration of the ECA
      segment is the standard treatment, endovascular treatment (EVT) can be considered
      if there is difficulty in identifying the source of bleeding in the injured
      regions that are difficult to operatively access. Here we treated a young patient
      who had hemorrhagic instability with hemorrhage-induced coagulopathy caused by a
      zone III cervical stab wound with a pseudoaneurysm from the main trunk of the
      ECA; the patient underwent EVT and successful hemostasis. A literature review
      based on the data available on PubMed was conducted, and 15 published reports of
      82 penetrating ECA injuries treated by EVT were identified. We concluded that EVT
      appears to be an effective surgical alternative for patients with hemorrhage
      induced coagulopathy caused by a ruptured ECA pseudoaneurysm after a cervical
      stab wound.

PMID- 29052834
TI  - Laparoscopic approach for removing a coin trapped in Meckel's diverticulum.
AB  - Foreign body ingestion is a common problem in children. Most of these foreign
      bodies spontaneously pass through the gastrointestinal tract. When there is a
      persistent foreign body in the abdomen, it is impossible to make a diagnosis
      without exploration. We herein present the case of a child who was admitted to
      our hospital with a coin trapped in Meckel's diverticulum and our laparoscopic
      approach in this case. The diagnosis of Meckel's diverticulum should be
      considered when there is a prolonged lodgment of a foreign body in the right
      lower quadrant, and the laparoscopic approach is the preferred choice in these
      cases.

PMID- 29052835
TI  - Role of percutaneous transhepatic biliary drainage in the management of blunt
      liver trauma: A case report.
AB  - The liver is the most commonly injured intra-abdominal organ after blunt trauma.
      The management of massive liver injury is complex. Percutaneous transhepatic
      biliary drainage is the first approach considered, particularly for proximal bile
      duct strictures after liver surgery. A 27-year-old female patient was transferred
      to our emergency department with grade V blunt injury. Regarding the patient's
      unresponsive hemodynamic instability, right hepatectomy was performed. The
      patient presented with benign biliary duct stricture after surgery that were
      treated via the percutaneous approach.

PMID- 29052836
TI  - Topical hemostatics for bleeding control in pre-hospital setting: Then and now.
AB  - Massive hemorrhage causes instant and early deaths because of hypovolemia.
      However, even if the victim makes it to the hospital, hypothermia, metabolic
      acidosis, and coagulation impairments caused by bleeding pose a great risk for
      survival. Many topical hemostatic agents are developed for neck, armpit, or groin
      injuries that are not amenable to tourniquet application and for extremity wounds
      to be used in conjunction with tourniquets. This paper focuses on those
      hemostatics that differ based on the action mechanism and are suitable for pre
      hospital setting and summarizes the latest recommendations regarding their usage.

PMID- 29052837
TI  - Research Review: Cognitive bias modification of interpretations in youth and its
      effect on anxiety: a meta-analysis.
AB  - BACKGROUND: Emerging evidence suggests that cognitive bias modification of
      interpretations (CBM-I) is effective in altering interpretation biases and
      reducing anxiety in adults. Less is known about the impact of CBM-I in young
      people, but some recent findings, including a meta-analysis of combined cognitive
      bias modification of interpretation and attention techniques, have cast doubt on
      its clinical utility. Given the current debate, this meta-analysis sought to
      establish the independent effects of CBM-I on interpretations biases and anxiety
      in youth. METHODS: Studies were identified through a systematic literature search
      of PsycINFO, Ovid MEDLINE, PsycARTICLES, Web of Science and EMBASE between
      January 1992 and March 2017. Eligible studies aimed to target interpretation
      biases; did not combine CBM-I with another intervention; included a control
      condition; randomly allocated participants to conditions; assessed interpretation
      bias and/or anxiety as an outcome; included individuals up to age 18; and did not
      present previously reported data. Reference lists of included articles were
      checked for further eligible studies, and authors were contacted for unpublished
      data. RESULTS: We identified 26 studies meeting eligibility criteria that
      included in the meta-analysis. CBM-I had moderate effects on negative and
      positive interpretations (g = -0.70 and g = -0.52, respectively) and a small but
      significant effect on anxiety assessed after training (g = -0.17) and after a
      stressor (g = -0.34). No significant moderators were identified. CONCLUSIONS: In
      contrast to previous meta-analytic findings, our results indicate that CBM-I has
      potential but weak anxiolytic effects in youth. Our findings suggest that it may
      be premature to disregard the potential value of CBM-I research and further
      research in this field is warranted.

PMID- 29052838
TI  - Annual Research Review: Early intervention for infants and young children with,
      or at-risk of, autism spectrum disorder: a systematic review.
AB  - BACKGROUND: There has been increased interest in early screening and intervention
      for young children with, or at risk of, autism spectrum disorder (ASD). This has
      generated a debate about the potential harms versus benefits of early
      identification and treatment. This review aims to identify the evidence base for
      early intervention in ASD. METHODS: A systematic review searching for randomised
      controlled trials (RCTs) of interventions for children up to 6 years of age with,
      or at risk of, ASD was undertaken. Characteristics and outcomes of included
      studies were collated and described in tabular format, and all included studies
      were rated according to the Cochrane Risk of Bias Tool. RESULTS: Forty-eight RCTs
      were identified, of which 40 were published since 2010. Most studies (n = 34)
      were undertaken in the United States. Included RCTs evaluated 32 different models
      of intervention. If blinding of participants and relevant personnel is overlooked
      as a source of bias, only six studies met criteria for low risk of bias across
      all domains of the Cochrane Risk of Bias Tool. The majority of studies had a
      relatively small sample size with only seven studies having a sample size >100.
      CONCLUSIONS: There has been a substantial increase in the number of RCTs
      evaluating early interventions in ASD. However, few studies, only 12.5% of the
      total, were rated as being at low risk of bias. Small sample size, unclear
      concealment of allocation and lack of clarity in the identification of the active
      ingredients in a diverse range of differently named treatment models were
      identified as challenges to the design, conduct and interpretation of studies.
      Improved co-ordination and design of studies is, therefore, required if future
      research in the field is to more clearly investigate the effects of early
      intervention for ASD.

PMID- 29052839
TI  - Effects of microRNA-206 and its target gene IGF-1 on sevoflurane-induced
      activation of hippocampal astrocytes in aged rats through the PI3K/AKT/CREB
      signaling pathway.
AB  - The study aims to explore the effects of microRNA-206 (miR-206) targeting IGF-1
      on the activation of hippocampal astrocytes in aged rats induced by sevoflurane
      through the PI3K/AKT/CREB signaling pathway. Wistar rats and astrocytes were
      divided into the normal/blank, sham/negative control (NC), sevoflurane (sevo),
      miR-206 mimics+sevo, miR-206 inhibitors+sevo, miR-206 NC+sevo, IGF-1 shRNA+sevo,
      and miR-206 inhibitors+IGF-1 shRNA+sevo groups. The Morris water maze test was
      exhibited to assess the cognitive functions. Glial fibrillary acidic protein
      (GFAP) expression was detected by immunofluorescence assay. Western blotting and
      RT-qPCR were used to detect the expression of miR-206, IGF-1, PI3K, AKT, CREB,
      pPI3K, pAKT, pCREB, cytochrome-c (Cyt-c), and caspase-3. Cell viability and
      apoptosis were detected by MTT assay and annexin V/PI double staining
      respectively. Mitochondrial transmembrane potential (MTP) were determined by flow
      cytometry. The IGF-1 shRNA+sevo group showed reduced miR-206 expression. Compared
      with the normal/blank group, the sevo, and miR-206 NC+sevo groups showed
      decreased miR-206 and GFAP expressions, cell viability and MTP but increased
      expressions of IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, Cyt-c and caspase-3,
      as well as cell apoptosis. Similar trends were observed in the miR-206
      inhibitors+sevo group when compared with the sevo group. The study provides
      evidence that miR-206 alleviates the inhibition of activation of hippocampal
      astrocytes in aged rats induced by sevoflurane by targeting IGT-1 through
      suppressing the PI3K/AKT/CREB signaling pathway.

PMID- 29052840
TI  - Crowd-Sourcing of Membrane Fission: How crowding of non-specialized membrane
      bound proteins contributes to cellular membrane fission.
AB  - Fission of cellular membranes is ubiquitous and essential for life. Complex
      protein machineries, such as the dynamin and ESCRT spirals, have evolved to
      mediate membrane fission during diverse cellular processes, for example, vesicle
      budding. A new study suggests that non-specialized membrane-bound proteins can
      induce membrane fission through mass action due to protein crowding. Because up
      to 2/3 of the mass of cellular membranes is contributed by proteins, membrane
      protein crowding is an important physiological parameter. Considering the
      complexity of membrane shape transitions during a fission reaction, spatial and
      temporal variability in protein distribution, and the abundance of intrinsically
      disordered regions in proteins on an invaginating membrane, protein crowding can
      have diverse consequences for fission in the cell. The question is, how and to
      what extent this mechanism combines with the action of dedicated fission
      machineries.

PMID- 29052841
TI  - Cognitive mechanisms of inhibitory control deficits in autism spectrum disorder.
AB  - BACKGROUND: Inhibitory control deficits are common in autism spectrum disorder
      (ASD) and associated with more severe repetitive behaviors. Inhibitory control
      deficits may reflect slower execution of stopping processes, or a reduced ability
      to delay the onset of behavioral responses in contexts of uncertainty. Previous
      studies have documented relatively spared stopping processes in ASD, but whether
      inhibitory control deficits in ASD reflect failures to delay response onset has
      not been systematically assessed. Further, while improvements in stopping
      abilities and response slowing are seen through adolescence/early adulthood in
      health, their development in ASD is less clear. METHODS: A stop-signal test (SST)
      was administered to 121 individuals with ASD and 76 age and IQ-matched healthy
      controls (ages 5-28). This test included 'GO trials' in which participants
      pressed a button when a peripheral target appeared and interleaved 'STOP trials'
      in which they were cued to inhibit button-presses when a stop-signal appeared at
      variable times following the GO cue. STOP trial accuracy, RT of the stopping
      process (SSRT), and reaction time (RT) slowing during GO trials were examined.
      RESULTS: Relative to controls, individuals with ASD had reduced accuracy on STOP
      trials. SSRTs were similar across control and ASD participants, but RT slowing
      was reduced in patients compared to controls. Age-related increases in stopping
      ability and RT slowing were attenuated in ASD. Reduced stopping accuracy and RT
      slowing were associated with more severe repetitive behaviors in ASD. DISCUSSION:
      Our findings show that inhibitory control deficits in ASD involve failures to
      strategically delay behavioral response onset. These results suggest that reduced
      preparatory behavioral control may underpin inhibitory control deficits as well
      as repetitive behaviors in ASD. Typical age-related improvements in inhibitory
      control during late childhood/early adolescence are reduced in ASD, highlighting
      an important developmental window during which treatments may mitigate cognitive
      alterations contributing to repetitive behaviors.

PMID- 29052842
TI  - Shear stress upregulates regeneration-related immediate early genes in liver
      progenitors in 3D ECM-like microenvironments.
AB  - The role of fluid stresses in activating the hepatic stem/progenitor cell
      regenerative response is not well understood. This study hypothesized that
      immediate early genes (IEGs) with known links to liver regeneration will be
      upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses
      on the order of those produced from elevated interstitial flow after partial
      hepatectomy. The objectives were: (1) to develop a shear flow chamber for
      application of fluid stress to LPCs in 3D culture; and (2) to determine the
      effects of fluid stress on IEG expression in LPCs. Two hours of shear stress
      exposure at ~4 dyn/cm2 was applied to LPCs embedded individually or as 3D
      spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared
      against static controls. Quantitative reverse transcriptase polymerase chain
      reaction was used to evaluate the effect of experimental treatments on gene
      expression. Twenty-nine genes were analyzed, including IEGs and other genes
      linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other
      regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in
      LPCs in response to fluid mechanical stress. LPCs maintained an early to
      intermediate stage of differentiation in spheroid culture in the absence of the
      hydrogel, and addition of the gel initiated cholangiocyte differentiation
      programs which were abrogated by the onset of flow. Collectively the flow
      upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative
      response. These results suggest that fluid stresses are potentially important
      regulators of the LPC-mediated regeneration response in liver.

PMID- 29052844
TI  - Synthesis of Pb9 (PO4 )6 /Ag3 PO4 Composite Photocatalysts with Enhanced Visible
      Light Photocatalytic Activity.
AB  - Pb9 (PO4 )6 /Ag3 PO4 photocatalysts with different amounts of Pb9 (PO4 )6 were
      successfully synthesised by the ion exchange method. The catalysts were
      characterized by X-ray diffractometry (XRD), High-resolution transmission
      electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), Brunauer-
      Emmett-Teller (BET), Fourier transform infrared spectrometry (FT-IS), and
      ultraviolet-visible (UV-vis) spectroscopy. All Pb9 (PO4 )6 /Ag3 PO4
      photocatalysts show much higher photocatalytic activities than pure Ag3 PO4 under
      visible light irradiation in the methyl-orange (MO) decomposition. Especially,
      the 3.0 wt% Pb9 (PO4 )6 /Ag3 PO4 photocatalyst shows the highest photoactivity
      and also high stability after five cycles. The MO degradation rate during each
      cycle is almost maintained at 97%. Photo-electrochemical measurement of
      photocatalysts verified that the enhancing photocatalytic activity was resulted
      from the electron-hole pair high separation. The photocatalytic activity
      enhancement of Pb9 (PO4 )6 /Ag3 PO4 is closely related to .OH, the main active
      oxygen species.

PMID- 29052843
TI  - Animal Models in Translational Research: Rosetta Stone or Stumbling Block?
AB  - Leading animal models are powerful tools for translational research, but they
      also present obstacles. Poorly conducted preclinical research in animals is a
      common cause of translational failure, but even when such research is well
      designed and carefully executed, challenges remain. In particular, dominant
      models may bias research directions, elide essential aspects of human disease,
      omit important context, or subtly shift research targets. Recognizing these
      stumbling blocks can help us find ways to avoid them: employing a wider range of
      models, incorporating more realistic environmental conditions, better aligning
      studies between animals and patients, and focusing on human biology and
      therapeutic goals. Such changes are costly; but insisting it would be impractical
      or unrealistic to change strategies offers no way out of the current impasse.
      Rather, we must acknowledge the obstacles as well as the advantages presented by
      core models, and direct some of our investments in translational research toward
      getting around them.

PMID- 29052845
TI  - The advanced glycation end product Nepsilon -carboxymethyllysine and its
      precursor glyoxal increase serotonin release from Caco-2 cells.
AB  - Advanced glycation end products (AGEs), comprising a highly diverse class of
      Maillard reaction compounds formed in vivo and during heating processes of foods,
      have been described in the progression of several degenerative conditions such as
      Alzheimer's disease and diabetes mellitus. Nepsilon -Carboxymethyllysine (CML)
      represents a well-characterized AGE, which is frequently encountered in a Western
      diet and is known to mediate its cellular effects through binding to the receptor
      for AGEs (RAGE). As very little is known about the impact of exogenous CML and
      its precursor, glyoxal, on intestinal cells, a genome-wide screening using a
      customized microarray was conducted in fully differentiated Caco-2 cells. After
      verification of gene regulation by qPCR, functional assays on fatty acid uptake,
      glucose uptake, and serotonin release were performed. While only treatment with
      glyoxal showed a slight impact on fatty acid uptake (P < 0.05), both compounds
      reduced glucose uptake significantly, leading to values of 81.3% +/- 22.8% (500
      MUM CML, control set to 100%) and 68.3% +/- 20.9% (0.3 MUM glyoxal). Treatment
      with 500 MUM CML or 0.3 MUM glyoxal increased serotonin release (P < 0.05) to
      236% +/- 111% and 264% +/- 66%, respectively. Co-incubation with the RAGE
      antagonist FPS-ZM1 reduced CML-induced serotonin release by 34%, suggesting a
      RAGE-mediated mechanism. Similarly, co-incubation with the SGLT-1 inhibitor
      phloridzin attenuated serotonin release after CML treatment by 32%, hinting at a
      connection between CML-stimulated serotonin release and glucose uptake. Future
      studies need to elucidate whether the CML/glyoxal-induced serotonin release in
      enterocytes might stimulate serotonin-mediated intestinal motility.

PMID- 29052846
TI  - Improvements of adolescent psychopathology after insomnia treatment: results from
      a randomized controlled trial over 1 year.
AB  - BACKGROUND: Adolescent insomnia can be treated effectively with cognitive
      behavioural therapy for insomnia (CBTI). However, little is known about effects
      of CBTI on psychopathology in adolescents. This study aimed to investigate
      whether (a) CBTI improves psychopathology in Internet- (IT) and face-to-face
      group treatment (GT) compared to waitlist (WL), (b) improvement in
      psychopathology can be attributed to reduced insomnia, (c) improvement in
      psychopathology remains stable for up to 1 year. METHODS: One hundred and sixteen
      participants (age = 15.6 years, 25% males) with DSM-5 insomnia, were randomly
      assigned to IT, GT or WL. CLINICAL TRIAL REGISTRATION:
      http://www.controlledtrials.com (ISRCTN33922163). Assessments of psychopathology,
      insomnia and objectively and subjectively measured sleep occurred at baseline,
      post-treatment, and at 2-, 6- and 12-month follow-up. Multilevel and mediation
      analyses were run to test hypotheses. The CBTI protocol, 'Sleeping Smart' for
      both IT and GT consisted of six weekly sessions and a booster session after 2
      months. RESULTS: Psychopathology symptoms, insomnia and sleep problems as
      measured by actigraphy and sleep logs decreased substantially in IT and GT
      compared with WL at 2-month follow-up with medium to large effect sizes (ESs).
      Psychopathology symptoms remained stable or further improved for up to 12-month
      follow-up. ESs at 12-month follow-up for IT and GT were respectively: affective
      (d = -0.87 and -0.97), anxiety (d = -0.81 for IT), somatic (d = -0.38 and d = 
      0.52), oppositional (d = -0.42 for GT) and attention deficit hyperactivity
      disorder (ADHD) problems (d = -0.47 and -0.46). Mediation analyses indicated that
      reduction of insomnia symptoms after CBTI fully mediated the effects of CBTI on
      affective and anxiety problems, and partially mediated the effect on ADHD
      problems. CONCLUSIONS: This is the first study demonstrating that Internet and
      face-to-face CBT for insomnia achieves long-term reduction in adolescent
      psychopathology and does so by improving insomnia. This finding can have profound
      implications for youth mental health care.

PMID- 29052847
TI  - Effects of oil content on the sensory, textural, and physical properties of pecan
      butter (Carya illinoinensis).
AB  - : It has been difficult to produce acceptable pecan butters as the high oil
      content results in a product that flows and separates too easily. The objective
      of this work was to create pecan butters with varying oil levels (50-70%) and
      determine which would give the most acceptable product. Consumers rated pecan
      butters with 55-60% oil the most acceptable, whether roasted or not.
      Acceptability varied most in terms of texture and spreadability, but not flavor.
      Under large deformation firmness varied from 51.8 g (70% oil) to 4,880 g (50%)
      oil, while "spreadability" ranged from 19.2 to 7748 (g/s). Samples with 70% oil
      had the lowest viscosity and were Newtonian. Pecan butters with 50-55% oil had
      high viscosity and were shear thinning. Yield stress decreased with oil content,
      ranging from 0.014 to 500 Pa. The storage modulus (G') increased from ~7 Pa for
      samples with 70% oil up to 260,000 Pa for those with 50% oil. In conjunction, tan
      delta decreased from 1 to 0.07, showing the products take on much more solid-like
      behavior as oil is removed. In conclusion, the rheological properties of pecan
      butter were quite sensitive to the amount of oil in the product. Differences in
      acceptability were primarily due to "texture" and "spreadability," suggesting
      there is a limited range of firmness and spreadability that consumers will deem
      acceptable. PRACTICAL APPLICATIONS: There has been considerable demand for
      butters and spreads made from a variety of culinary nuts. Pecans generally have
      too much oil (~70%) to make a product with proper consistency and stability. In
      this study, some of the oil was removed to overcome this problem. It was found
      that pecan butter with 55-60% oil was most acceptable to consumers and with the
      level of firmness, yield stress, and spreadability most similar to commercial nut
      butters. The oil was relatively simple to remove from unroasted nuts, thus
      manufacturers could easily produce more acceptable pecan butter for the market.

PMID- 29052848
TI  - Beyond Amyloid - Widening the View on Alzheimer's Disease.
AB  - For 25 years, the amyloid cascade hypothesis, based on the finding that mutations
      in the amyloid precursor protein are closely linked to familial forms of
      Alzheimer's disease (AD), dominated the research on this disease. Recent failures
      of clinical anti-amyloidogenic trials, however, substantially support the
      reasoning (i) that the pathomechanisms that trigger familial AD, namely the
      generation, aggregation, and deposition of amyloid beta, cannot necessarily be
      extrapolated to sporadic cases and (ii) that amyloid beta represents a prominent
      histopathological feature in AD but not its exclusive causative factor. In autumn
      2016, the Volkswagen Foundation hosted the Herrenhausen Symposium 'Beyond Amyloid
      - Widening the View on Alzheimer's Disease' in Hannover, Germany, to bring
      together current knowledge on cellular and molecular processes that contribute to
      AD pathogenesis independent of or alongside with the amyloid biochemistry. The
      following mini review series was authored by key speakers at the meeting, and
      highlights some of the mechanisms potentially involved in AD etiology that
      provide alternative viewpoints and mechanisms beyond the amyloid cascade
      hypothesis. This article is part of the series "Beyond Amyloid".

PMID- 29052849
TI  - Clinical applications of IDDSI framework for texture recommendation for dysphagia
      patients.
AB  - : Dysphagia is a highly prevalent eating and swallowing disorder among elderly
      people, impacting negatively on the health and well-being of those afflicted.
      With increasing populations of elderly people, food industries are under growing
      pressure to produce appropriately texture-modified food for safe consumption by
      these vulnerable populations. Recently published International Dysphagia Diet
      Standardisation Initiative (IDDSI) framework provides a new global guideline on
      texture modification and standardization for dysphagia patients. This work was
      designed to test the feasibility of IDDSI framework for clinical applications by
      assessing the correlation between swallowing capability of dysphagia patients and
      the IDDSI texture levels. Altogether 26 elderly subjects were recruited and
      assessed for their dysphagia grades using the Water Drinking Test. Subjects were
      provided with fluid samples constituted at different consistencies from a
      commercial product and swallowing performance (time of swallowing, number of
      swallows, and number of coughs) was monitored and recorded. Correlations among
      swallowing capability parameters were observed. Most importantly, results from
      this work clearly demonstrated that the severity of dysphagia by water-based
      swallow tests correlates positively with the IDDSI fluid thickness aimed at
      reducing dysphagia symptoms in those patients, confirming the reliability and
      feasibility of IDDSI framework for clinical applications. PRACTICAL APPLICATIONS:
      Swallowing disorder or dysphagia occurs commonly among many elderly people and
      imposes negative impacts on their health and well-being. Medical professionals
      can diagnose eating and swallowing capability in a qualitative manner, but have
      difficulty in making diet recommendation because of the lack of texture guidance.
      This work confirmed the feasibility of IDDSI framework for clinical and bedside
      applications. The correlation between the capability grades of swallowing and
      IDDSI texture levels established in this work provides a useful measure for such
      applications.

PMID- 29052850
TI  - Curcumin, hemostasis, thrombosis, and coagulation.
AB  - Atherothrombotic cardiovascular disease is a major cause of mortality throughout
      the world. Platelet activation and aggregation play a central role in hemostasis
      and thrombosis. Herbal medicines have been traditionally used in the management
      of cardiovascular disease and can help in modifying its progression, particularly
      in hemostasis and the coagulation process, as well as altering platelet function
      tests and some coagulation parameters. Curcumin is a polyphenol derived from the
      Curcuma longa plant and has been used extensively in complementary and
      alternative medicine, as it is nontoxic and safe with various therapeutic
      properties. Modern scientific research has demonstrated its anti-inflammatory,
      antioxidant, anti-carcinogenic, antithrombotic, and cardiovascular protective
      effects. The present study reviewed previous studies in the literature, which
      support the positive activity of curcumin in hemostasis, anticoagulation, and
      fibrinolysis. We also presented molecular mechanisms associated with the
      antiplatelet and anticoagulant activities of curcumin and potential implications
      for the treatment of cardiovascular disease.

PMID- 29052851
TI  - Editorial: risk stratification for endoscopic surveillance of metachronous
      gastric cancer after endoscopic resection-Authors' reply.

PMID- 29052852
TI  - Editorial: risk stratification for endoscopic surveillance of metachronous
      gastric cancer after endoscopic resection.

PMID- 29052853
TI  - Editorial: hepatitis C virus (HCV) disease progression - HCV cure and the
      elimination of the "ethnic slope". Authors' reply.

PMID- 29052854
TI  - Letter: enteral nutrition therapy for the induction of remission in paediatric
      Crohn's disease.

PMID- 29052856
TI  - ERRATUM.

PMID- 29052855
TI  - Letter: enteral nutrition therapy for the induction of remission in paediatric
      Crohn's disease-Authors' reply.

PMID- 29052857
TI  - Editorial: rifaximin in cirrhosis-is this what we've been waiting for? Authors'
      reply.

PMID- 29052858
TI  - Editorial: rifaximin in cirrhosis - is it what we've been waiting for?

PMID- 29052859
TI  - Letter: low-FODMAP diet for exercise-induced gastrointestinal syndrome-Authors'
      reply.

PMID- 29052860
TI  - Letter: the risk of cancer in patients with gastric intestinal metaplasia.

PMID- 29052861
TI  - Letter: addition of methotrexate neither restores clinical response nor improves
      the pharmacokinetic profile of vedolizumab-treated patients.

PMID- 29052862
TI  - Editorial: hepatitis C virus (HCV) disease progression - HCV cure and the
      elimination of the "ethnic slope".

PMID- 29052863
TI  - Letter: low-FODMAP diet for exercise-induced gastrointestinal syndrome.

PMID- 29052864
TI  - Short-term hypoxia upregulated Mas receptor expression to repress the AT1 R
      signaling pathway and attenuate Ang II-induced cardiomyocyte apoptosis.
AB  - Hypertension-stimulated cardiac hypertrophy and apoptosis play critical roles in
      the progression of heart failure. Our previous study suggested that hypertensive
      angiotensin II (Ang II) enhanced insulin-like growth factor receptor II (IGF-IIR)
      expression and cardiomyocyte apoptosis, which are involved JNK activation,
      sirtuin1 (SIRT1) degradation, and heat-shock transcription factor 1 (HSF1)
      acetylation. Moreover, previous studies have implied that short-term hypoxia
      (STH) might exert cardioprotective effects. However, the effects of STH on Ang II
      induced cardiomyocyte apoptosis remain unknown. In this study, we found that STH
      reduced myocardial apoptosis caused by Ang II via upregulation of the Mas
      receptor (MasR) to inhibit the AT1 R signaling pathway. STH activates MasR to
      counteract the Ang II pro-apoptotic signaling cascade by inhibiting IGF-IIR
      expression via downregulation of JNK activation and reduction of SIRT1
      degradation. Hence, HSF could remain deacetylated, and repress IGF-IIR
      expression. These effects decrease the activation of downstream pro-apoptotic and
      hypertrophic cascades and protect cardiomyocytes from Ang II-induced injury. In
      addition, we also found that silencing MasR expression enhanced Ang II-induced
      cardiac hypertrophy and the apoptosis signaling pathway. These findings suggest a
      critical role for MasR in cardiomyocyte survival. Altogether, our findings
      indicate that STH protects cardiomyocytes from Ang II-stimulated apoptosis. The
      protective effects of STH are associated with the upregulation of MasR to inhibit
      AT1 R signaling. STH could be a potential therapeutic strategy for cardiac
      diseases in hypertensive patients.

PMID- 29052865
TI  - Research Review: Is anxiety associated with negative interpretations of ambiguity
      in children and adolescents? A systematic review and meta-analysis.
AB  - BACKGROUND: The tendency to interpret ambiguity as threat (negative
      interpretation) has been implicated in cognitive models of anxiety. A significant
      body of research has examined the association between anxiety and negative
      interpretation, and reviews suggest there is a robust positive association in
      adults. However, evidence with children and adolescents has been inconsistent.
      This study aimed to provide a systematic quantitative assessment of the
      association between anxiety and negative interpretation in children and
      adolescents. METHOD: Following systematic searches and screening for eligibility,
      345 effects sizes from 77 studies were meta-analysed. RESULTS: Overall a medium
      positive association was found between anxiety and negative interpretation in
      children and adolescents (  CONCLUSIONS: Results extend findings from adult
      literature by demonstrating an association in children and adolescents with
      evidence for content specificity in the association. Age effects imply a role for
      development. Results raise considerations for when and for whom clinical
      treatments for anxiety focusing on interpretation bias are appropriate. The vast
      majority of studies included in the review have used correlational designs and
      there are a limited number of studies with young children. The results should be
      considered with these limitations in mind.

PMID- 29052868
TI  - Sequence variants in hidradenitis suppurativa: in search of the pathogenic
      mechanisms.

PMID- 29052866
TI  - RUNX-mediated growth arrest and senescence are attenuated by diverse mechanisms
      in cells expressing RUNX1 fusion oncoproteins.
AB  - RUNX gene over-expression inhibits growth of primary cells but transforms cells
      with tumor suppressor defects, consistent with reported associations with tumor
      progression. In contrast, chromosomal translocations involving RUNX1 are
      detectable in utero, suggesting an initiating role in leukemias. How do cells
      expressing RUNX1 fusion oncoproteins evade RUNX-mediated growth suppression?
      Previous studies showed that the TEL-RUNX1 fusion from t(12;21) B-ALLs is unable
      to induce senescence-like growth arrest (SLGA) in primary fibroblasts while
      potent activity is displayed by the RUNX1-ETO fusion found in t(8;21) AMLs. We
      now show that SLGA potential is suppressed in TEL-RUNX1 but reactivated by
      deletion of the TEL HLH domain or mutation of a key residue (K99R). Attenuation
      of SLGA activity is also a feature of RUNX1-ETO9a, a minor product of t(8;21)
      translocations with increased leukemogenicity. Finally, while RUNX1-ETO induces
      SLGA it also drives a potent senescence-associated secretory phenotype (SASP),
      and promotes the immortalization of rare cells that escape SLGA. Moreover, the
      RUNX1-ETO SASP is not strictly linked to growth arrest as it is largely
      suppressed by RUNX1 and partially activated by RUNX1-ETO9a. These findings
      underline the heterogeneous nature of premature senescence and the multiple
      mechanisms by which this failsafe process is subverted in cells expressing RUNX1
      oncoproteins.

PMID- 29052870
TI  - Image Gallery: Purpuric fixed drug eruption from ornidazole showing
      leukocytoclastic vasculitis.

PMID- 29052871
TI  - A path through the reticulate pigmentation disorder jungle.

PMID- 29052872
TI  - Further progress for therapeutic solutions in psoriasis.

PMID- 29052873
TI  - First-line systemic treatment of psoriasis: staying conventional or going
      biologic?

PMID- 29052874
TI  - Image Gallery: A case of blastic plasmacytoid dendritic cell neoplasm.

PMID- 29052875
TI  - Clinical significance of parvovirus B19 DNA in cutaneous biopsies.

PMID- 29052876
TI  - Image Gallery: Cutaneous metastases from hidden carcinoma of the penis.

PMID- 29052877
TI  - Personalized melanoma genomic risk information:perception of shared risk
      initiates sharing with family.

PMID- 29052878
TI  - Staphylococcus aureus and psoriasis: time for a re-appraisal?

PMID- 29052880
TI  - Endoscopic characteristics of oesophagus involvement in mucous membrane
      pemphigoid.

PMID- 29052881
TI  - A foot tumour as late cutaneous Lyme borreliosis: a new entity or a variant of an
      inflammatory proliferative reaction to Borrelia burgdorferi?

PMID- 29052882
TI  - Image Gallery: Merkel cell carcinoma under the rainbow.

PMID- 29052883
TI  - Getting tired of psoriasis?

PMID- 29052884
TI  - Systematic reviews: let's keep them trustworthy.

PMID- 29052886
TI  - Image Gallery: Nail involvement in syphilis: the great forgotten.

PMID- 29052887
TI  - Image Gallery: Porokeratosis under the dermoscopic furrow ink test and
      ultraviolet light.

PMID- 29052888
TI  - Cost-effectiveness of HLA-B*15:02 screening in Malaysia.

PMID- 29052889
TI  - Image Gallery: Flagellate bullous exanthem in chikungunya.

PMID- 29052891
TI  - Image Gallery: Dissecting cellulitis of the scalp following anabolic steroid use.

PMID- 29052890
TI  - Guidelines for the management of acne: recommendations from a French
      multidisciplinary group.

PMID- 29052892
TI  - Introducing the new Evidence-Based Dermatology section.

PMID- 29052894
TI  - Image Gallery: Symmetrical bilateral acrometastases of the great toes in
      metastatic renal cell carcinoma.

PMID- 29052895
TI  - Cover Image: Capturing the architectural beauty of the dermal elastic fibre
      network.

PMID- 29052896
TI  - The evolving universe of BRAF mutations in melanoma.

PMID- 29052897
TI  - Acne guidelines: pearls, pitfalls and questions.

PMID- 29052898
TI  - Image Gallery: A case of chronic eosinophilic leukaemia.

PMID- 29052899
TI  - Image Gallery: Unusual images of monilethrix: the eyebrows and the biopsy.

PMID- 29052900
TI  - Towards a better categorization of patients with chronic urticaria.

PMID- 29052901
TI  - Cardiometabolic disease in atopic dermatitis: the heart of the matter.

PMID- 29052902
TI  - Towards the use of precision medicine in predicting cutaneous squamous cell
      carcinoma risk among solid organ transplant recipients.

PMID- 29052903
TI  - Image Gallery: Unilaterally dominant acrokeratoelastoidosis (punctate
      palmoplantar keratoderma type 3).

PMID- 29052904
TI  - Unravelling the links between malignancy, cytokines and neutrophilic eruptions.

PMID- 29052905
TI  - Metabolic changes in patients with prostate cancer during androgen deprivation
      therapy.
AB  - Androgen deprivation therapy continues to be widely used for the treatment of
      prostate cancer despite the appearance of new-generation androgen-receptor
      targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms
      in patients with metastatic prostate cancer and might have a survival benefit in
      some patients, but it causes undesirable changes in lipid, glucose, muscle or
      bone metabolism. These metabolic changes could lead to new onset or worsening of
      diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular
      disease, sarcopenia or fracture. Several studies examining the influence of
      androgen deprivation therapy in Japanese patients with prostate cancer also
      showed that metabolic changes, such as weight gain, dyslipidemia or fat
      accumulation, can occur as in patients in Western countries. Efforts to decrease
      these unfavorable changes and events are important. First, overuse of androgen
      deprivation therapy for localized or elderly prostate cancer patients should be
      reconsidered. Second, intermittent androgen deprivation therapy might be
      beneficial for selected patients who suffer from impaired quality of life as a
      result of continuous androgen deprivation therapy. Third, education and
      instruction, such as diet or exercise, to decrease metabolic changes before
      initiating androgen deprivation therapy is important, because metabolic changes
      are likely to occur in the early androgen deprivation therapy period. Fourth,
      routine monitoring of weight, laboratory data or bone mineral density during
      androgen deprivation therapy are required to avoid unfavorable events.

PMID- 29052906
TI  - Evaluation of adherence and tolerability of prolonged-release tacrolimus
      (AdvagrafTM) in kidney transplant patients in Germany: A multicenter,
      noninterventional study.
AB  - This study assessed adherence to prolonged-release tacrolimus (PR-T)-based
      immunosuppression during routine maintenance of renal transplant recipients in
      Germany. Patients had received PR-T for >=1 month at inclusion. Data were
      collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4)
      months. Composite primary endpoint: nonadherence at V4, defined as self-reported
      nonadherence on the Basel Assessment of Adherence with Immunosuppressive
      Medication Scale (BAASIS(c) ), investigator-rated nonadherence, and/or V4
      tacrolimus trough level outside a predefined range. Secondary endpoints:
      individual BAASIS items, incidence of rejection, kidney function, and safety.
      Overall, 153 adult kidney recipients (mean [standard deviation] time post
      transplant 5.8 [4.6] years) were included. Nonadherence was high at V4 (67.7%
      [95% confidence interval 58.9%, 75.6%]). Medication-taking adherence was 86.9%
      and 91.3% at V1 and V4, respectively; adherence to timing of medication intake
      was 58.2% and 58.3%, with little evidence of missed doses/drug holidays.
      Investigators rated adherence "good" in 85.6% of patients (V4). Two (1.3%)
      patients had acute rejection episodes. Kidney function remained stable (mean
      creatinine clearance, V1: 62.1 mL/min; V4: 65.3 mL/min). Investigators rated
      effectiveness of PR-T as "very good"/"good" in 91.5% of patients. Most patients
      (94.7%) found PR-T dosing more convenient than immediate-release tacrolimus. PR-T
      was well tolerated with high medication persistence.

PMID- 29052907
TI  - Organic Diode Rectifiers Based on a High-Performance Conjugated Polymer for a
      Near-Field Energy-Harvesting Circuit.
AB  - Organic diodes manufactured on a plastic substrate capable of rectifying a high
      frequency radio-frequency identification signal (13.56 MHz), with sufficient
      power to operate an interactive smart tag, are reported. A high-performance
      conjugated semiconductor (an indacenodithiophene-benzothiadiazole copolymer) is
      combined with a carefully optimized architecture to satisfy the electrical
      requirements for an organic-semiconductor-based logic chip.

PMID- 29052908
TI  - HBxAg suppresses cell apoptosis and promotes the secretion of placental hormones
      in human placental trophoblasts via activation of the EGFR/Akt pathway.
AB  - The aim of this study is to investigate the role of Hepatitis B virus x (HBx) in
      the growth and secretion of human placental trophoblasts. Firstly, placenta
      tissues were collected from pregnant HBV carriers with various viral loads. The
      results of immunohistochemical technique showed that the HBx protein and pEGFR
      protein levels were both markedly increased with the viral load elevation. Then,
      a placental trophoblast cell strain (JEG-3-HBx), which stably expressed HBx mRNA
      and protein, was established with the pcDNA-HBx transfection followed by the G418
      selection. The JEG-3-HBx strain displayed distinct activation of the EGFR/AKT
      pathway, a lower level of cell apoptosis, and higher secretion levels of
      placental hormones, including human chorionic gonadotropin (hCG), progesterone,
      estrogen and beta-endorphin. Subsequently, HBx siRNA was used to silence the HBx
      gene in the JEG-3-HBx strain. Our data showed that the HBx siRNA transfection
      markedly suppressed the activation of the EGFR/AKT pathway, promoted cell
      apoptosis, and reduced the secretion of the placental hormones. Finally, EGF was
      applied to simulate the JEG-3-HBx strain with or without the HBx siRNA
      transfection. EGF treatment counteracted the reduction of cell apoptosis and the
      suppression of hormone secretion caused by HBx siRNA in the cell strain. In
      conclusion, the pEGFR protein was robustly upregulated in HBx-infected human
      placenta tissues and trophoblast cells. HBx reduces cell apoptosis and promotes
      the secretion of placental hormones in human placental trophoblast cells via
      activation of the EGFR/Akt pathway.

PMID- 29052909
TI  - Allosteric control of a bacterial stress response system by an anti-sigma factor.
AB  - Bacterial signal transduction systems commonly use receiver (REC) domains, which
      regulate adaptive responses to the environment as a function of their
      phosphorylation state. REC domains control cell physiology through diverse
      mechanisms, many of which remain understudied. We have defined structural
      features that underlie activation of the multi-domain REC protein, PhyR, which
      functions as an anti-anti-sigma factor and regulates transcription of genes
      required for stress adaptation and host-microbe interactions in
      Alphaproteobacteria. Though REC phosphorylation is necessary for PhyR function in
      vivo, we did not detect expected changes in inter-domain interactions upon
      phosphorylation by solution X-ray scattering. We sought to understand this result
      by defining additional molecular requirements for PhyR activation. We uncovered
      specific interactions between unphosphorylated PhyR and an intrinsically
      disordered region (IDR) of the anti-sigma factor, NepR, by solution NMR
      spectroscopy. Our data support a model whereby nascent NepR(IDR)-PhyR
      interactions and REC phosphorylation coordinately impart the free energy to shift
      PhyR to an open, active conformation that binds and inhibits NepR. This mechanism
      ensures PhyR is activated only when NepR and an activating phosphoryl signal are
      present. Our study provides new structural understanding of the molecular
      regulatory logic underlying a conserved environmental response system.

PMID- 29052910
TI  - Cell proliferation is associated with intensity of tumor budding in oral squamous
      cell carcinoma.
AB  - BACKGROUND: Tumor budding is a morphological marker of cancer invasion, defined
      as the presence of isolated or small clusters of neoplastic cells at the tumor
      invasive front. This study aimed to evaluate the association between intensity of
      tumor budding and cell proliferation in oral squamous cell carcinoma (OSCC).
      METHODS: Immunohistochemistry was employed in 163 OSCC samples to detect the cell
      proliferation marker Ki-67 and multicytokeratin (to identify OSCC cells in tumor
      budding evaluation). The Mann-Whitney test was used to evaluate differences in
      the cell proliferation index between samples with high-intensity tumor budding
      and samples with low-intensity or no tumor budding. In samples with high
      intensity tumor budding, the Wilcoxon test was used to evaluate differences in
      the cell proliferation index between the budding area and the area outside the
      budding. The chi-square test assessed the association between cell proliferation
      index and intensity of tumor budding. RESULTS: The cell proliferation index was
      higher in samples with high-intensity tumor budding than in samples with low
      intensity or no tumor budding (P < .05). Tumors with high-intensity tumor budding
      showed a higher cell proliferation index in the budding area than in the area
      outside the budding (P < .05). Finally, samples showing high-intensity tumor
      budding were associated with high cell proliferation index (P < .05). CONCLUSION:
      Cell proliferation is positively associated with intensity of tumor budding in
      OSCC. Moreover, in tumors showing high-intensity tumor budding, the budding area
      is the location of higher cell proliferation. These findings reinforce the
      hypothesis that tumor budding is associated with the biological behavior of OSCC.

PMID- 29052911
TI  - External-Field-Induced Gradient Wetting for Controllable Liquid Transport: From
      Movement on the Surface to Penetration into the Surface.
AB  - External-field-responsive liquid transport has received extensive research
      interest owing to its important applications in microfluidic devices, biological
      medical, liquid printing, separation, and so forth. To realize different levels
      of liquid transport on surfaces, the balance of the dynamic competing processes
      of gradient wetting and dewetting should be controlled to achieve good
      directionality, confined range, and selectivity of liquid wetting. Here, the
      recent progress in external-field-induced gradient wetting is summarized for
      controllable liquid transport from movement on the surface to penetration into
      the surface, particularly for liquid motion on, patterned wetting into, and
      permeation through films on superwetting surfaces with external field cooperation
      (e.g., light, electric fields, magnetic fields, temperature, pH, gas, solvent,
      and their combinations). The selected topics of external-field-induced liquid
      transport on the different levels of surfaces include directional liquid motion
      on the surface based on the wettability gradient under an external field, partial
      entry of a liquid into the surface to achieve patterned surface wettability for
      printing, and liquid-selective permeation of the film for separation. The future
      prospects of external-field-responsive liquid transport are also discussed.

PMID- 29052912
TI  - Clinicopathologic significance of ROCK2 expression in oral squamous cell
      carcinomas.
AB  - BACKGROUND: Rho-associated coiled-coil kinase 2 (ROCK2) is an oncoprotein that
      controls cytoskeleton organization and acts as prognostic marker in different
      types of solid tumors. ROCK2 overexpression is also observed in cancer-associated
      fibroblasts (CAF), which suggests its relevance within the tumor
      microenvironment. This study aimed to access the prognostic value of ROCK2 in
      oral squamous cell carcinomas (OSCCs) and its association with CAF density.
      METHODS: Rho-associated coiled-coil kinase 2 immunohistochemical analysis was
      applied in 93 OSCC samples from 2 centers in Brazil and Finland. The samples were
      also stained for isoform alpha of smooth muscle actin (alpha-SMA) to characterize
      the presence of CAF in the tumor stroma. Clinicopathological associations were
      analyzed using Chi-squared test, survival curves were constructed according to
      the Kaplan-Meier method, and Cox proportional hazard model was applied for
      multivariate survival analysis. RESULTS: Advanced clinical stage (P = .002) and
      increased density of CAF (P = .002) were significantly associated with high ROCK2
      expression. The high expression of ROCK2 was also associated with shortened
      disease-specific survival (HR: 2.22, 95% CI: 1.15-4.38, P = .04), but the
      association did not withstand the Cox multivariate survival analysis.
      CONCLUSIONS: The findings suggest that high ROCK2 expression in OSCC is
      associated with advanced disease and follows the increase in CAF density, which
      may be important for tumor progression.

PMID- 29052913
TI  - A Pure Polyproline Type I-like Peptoid Helix by Metal Coordination.
AB  - Peptoids, N-substituted glycine oligomers, are an important class of foldamers
      that can adopt polyproline-type helices (PP-I and PP-II), given that the majority
      of their sequence consists of chiral, bulky side chains. Herein a new approach
      for the stabilization of a pure PP-I-like peptoid helix through metal
      coordination is introduced. A systematic spectroscopic study was performed on a
      series of peptoid heptamers bearing two 8-hydroxyquinoline ligands at fixed
      positions, and a mixture of chiral benzyl and alkyl substituents in varied
      positions along the peptoid backbone. When the benzyl groups are located at the
      3rd and 4th positions, the peptoid (7P6) gives upon Cu2+ binding a circular
      dichroism (CD) signal similar to that of a PP-I helix. Exciton couplet CD
      spectroscopy and EPR spectroscopy, as well as modifications to the length of 7P6
      and derivatization through acetylation provided insights into the unique folding
      of 7P6 upon Cu binding, showing that it is led by two competing driving forces,
      namely coordination geometry and sequence.

PMID- 29052914
TI  - Nanosegregated Chiral Materials with Self-Assembled Hierarchical Mesophases:
      Effect of Thermotropic and Photoinduced Polymorphism in Rodlike Molecules.
AB  - Supramolecular chirality in a binary mixture of achiral bent-core (BC) and
      achiral rodlike mesogens was observed. Three different nanosegregated mesophases
      were determined in the binary system, and meaningful changes in circular
      dichroism (CD) were detected near the phase-transition temperatures of the
      rodlike mesogens. The highest CD intensity in the binary system was noted in the
      nanosegregated mesophase, in which the BC mesogens were in the helical
      nanofilament (HNF) phase and the rodlike mesogens were in the smectic A phase.
      The supramolecular chirality in the binary mixture was attributed to the self
      assembled hierarchical chiral superstructures. Based on the experimental results,
      plausible scenarios for the chiral superstructures of the rodlike molecules
      embedded in the HNF networks are suggested. In addition, a system comprising BC
      and rodlike molecules doped with a photoresponsive compound exhibited remarkable
      photoswitching of CD intensity. According to the isothermal photoinduced phase
      transition of the embedded molecules in BC molecular HNFs, the observed CD
      intensities can be dynamically and reversibly modulated. Such a material with
      easily controllable functionality is of considerable interest in the field of
      materials science.

PMID- 29052915
TI  - Disease burden of mild asthma in China.
AB  - BACKGROUND AND OBJECTIVE: The impact, treatment patterns and control of mild
      asthma are poorly understood for Chinese patients. This study describes the
      characteristics, therapeutic interventions and burden of mild asthma on patients
      residing in major cities of China. METHODS: The Respiratory Disease Specific
      Program 2015, a cross-sectional survey, was conducted with Chinese physicians and
      their patients. The survey assessed clinical characteristics, asthma symptoms,
      exacerbations, rescue inhaler usage, treatment adherence, asthma control, work
      and activity impairments and healthcare utilization for patients prescribed
      Global Initiative for Asthma (GINA) Step 1 or 2 treatment defined mild asthma.
      RESULTS: From a total sample of 988 patients, 229 patients met the criteria for
      mild asthma, with 25.3% classified as Step 1 and 74.7% as Step 2. Overall, 12.6%
      of patients were considered of high adherence to prescribed treatment. Physicians
      reported that 75% of patients overall were well controlled, although well
      controlled asthma as defined by GINA was achieved in only 14.2% of patients.
      26.5% of patients indicated daily use of as-needed rescue medication in the last
      4 weeks. 17.8% of patients experienced >=1 exacerbations in the last 12 months
      and impaired work productivity was 27.2% overall. CONCLUSION: Less than 15% of
      patients were well controlled according to GINA criteria despite physicians
      reporting the majority of patients were well controlled. Over one-fourth of
      patients relied on daily rescue inhaler medication, while exacerbation frequency
      and work and activity impairment were higher than might reasonably be expected in
      a mild asthmatic population.

PMID- 29052916
TI  - Directed Self-Assembly of Liquid-Crystalline Molecular Building Blocks for Sub-5
      nm Nanopatterning.
AB  - The thin-film directed self-assembly of molecular building blocks into oriented
      nanostructure arrays enables next-generation lithography at the sub-5 nm scale.
      Currently, the fabrication of inorganic arrays from molecular building blocks is
      restricted by the limited long-range order and orientation of the materials, as
      well as suitable methodologies for creating lithographic templates at sub-5 nm
      dimensions. In recent years, higher-order liquid crystals have emerged as
      functional thin films for organic electronics, nanoporous membranes, and
      templated synthesis, which provide opportunities for their use as lithographic
      templates. By choosing examples from these fields, recent progress toward the
      design of molecular building blocks is highlighted, with an emphasis on liquid
      crystals, to access sub-5 nm features, their directed self-assembly into oriented
      thin films, and, importantly, the fabrication of inorganic arrays. Finally,
      future challenges regarding sub-5 nm patterning with liquid crystals are
      discussed.

PMID- 29052918
TI  - Contributions of recombination and repair proteins to telomere maintenance in
      telomerase-positive and negative Ustilago maydis.
AB  - Homologous recombination and repair factors are known to promote both telomere
      replication and recombination-based telomere extension. Herein, we address the
      diverse contributions of several recombination/repair proteins to telomere
      maintenance in Ustilago maydis, a fungus that bears strong resemblance to mammals
      with respect to telomere regulation and recombination mechanisms. In telomerase
      positive U. maydis, deletion of rad51 and blm separately caused shortened but
      stably maintained telomeres, whereas deletion of both engendered similar telomere
      loss, suggesting that the repair proteins help to resolve similar problems in
      telomere replication. In telomerase-negative cells, the loss of Rad51 or Brh2
      caused accelerated senescence and failure to generate survivors on semi-solid
      medium. However, slow growing survivors can be isolated through continuous liquid
      culturing, and these survivors exhibit type II-like as well as ALT-like telomere
      features. In contrast, the trt1Delta blmDelta double mutant gives rise to
      survivors as readily as the trt1Delta single mutant, and like the single mutant
      survivors, exhibit almost exclusively type I-like telomere features. In addition,
      we observed direct physical interactions between Blm and two telomere-binding
      proteins, which may thus recruit or regulate Blm at telomeres. Our findings
      provide the basis for further analyzing the interplays between telomerase,
      telomere replication, and telomere recombination.

PMID- 29052919
TI  - OAMDP, a novel podophyllotoxin derivative, induces apoptosis, cell cycle arrest
      and autophagy in hepatoma HepG2 cells.
AB  - 4beta-(1,3,4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin (OAMDP), a novel
      podophyllotoxin derivative, has demonstrated potent anti-tumor activity with
      significant cytotoxic effect. Here, we report the anti-proliferative effect of
      OAMDP, for which OAMDP could suppress the proliferation of HepG2 cells (human
      hepatoma cell line) in a dose- and time-dependent manner. After treating with
      OAMDP, cell apoptosis was confirmed by Annexin V-FITC/PI double staining assay.
      Furthermore, flow cytometry analysis revealed the loss of mitochondrial membrane
      potential and the increase of intracellular reactive oxygen species in HepG2
      cells. OAMDP increased apoptotic cell population with induction of Bax,
      cytochrome c (cyt-c), caspase-9, caspase-3, PARP1 and the reduction of Bcl-2 and
      p-Akt protein expressions. The MAPK family, JNK, ERK, p38, p-JNK, p-ERK, p-p38,
      were also regulated by OAMDP in HepG2 cells. Moreover, cell cycle analysis showed
      that OAMDP induced S or G2/M phase arrest through modulation of cycle regulatory
      proteins. In addition, MDC staining and LC3 protein expression indicated that
      autophagy was induced by OAMDP in HepG2 cells. To sum up, our results suggested
      that OAMDP, with the ability to induce autophagy, causing cell cycle arrest and
      apoptosis, has potential to become a novel anti-tumor agent.

PMID- 29052920
TI  - Treatment doses in idiopathic pulmonary fibrosis: The devil is in the detail.

PMID- 29052917
TI  - Post-translational modifications as key regulators of apicomplexan biology:
      insights from proteome-wide studies.
AB  - Parasites of the Apicomplexa phylum, such as Plasmodium spp. and Toxoplasma
      gondii, undergo complex life cycles involving multiple stages with distinct
      biology and morphologies. Post-translational modifications (PTMs), such as
      phosphorylation, acetylation and glycosylation, regulate numerous cellular
      processes, playing a role in every aspect of cell biology. PTMs can occur on
      proteins at any time in their lifespan and through alterations of target protein
      activity, localization, protein-protein interactions, among other functions,
      dramatically increase proteome diversity and complexity. In addition, PTMs can be
      induced or removed on changes in cellular environment and state. Thus, PTMs are
      likely to be key regulators of developmental transitions, biology and
      pathogenesis of apicomplexan parasites. In this review we examine the roles of
      PTMs in both parasite-specific and conserved eukaryotic processes, and the
      potential crosstalk between PTMs, that together regulate the intricate lives of
      these protozoa.

PMID- 29052921
TI  - A concept analysis of the term migrant women in the context of pregnancy.
AB  - AIM: This paper explores the concept of migrant women as used in European
      healthcare literature in context of pregnancy to provide a clearer understanding
      of the concept for use in research and service delivery. METHODS: Walker and
      Avant's method of concept analysis. RESULTS: The literature demonstrates
      ambiguity around the concept; most papers do not provide an explicit or detailed
      definition of the concept. They include the basic idea that women have moved from
      an identifiable region/country to the country in which the research is undertaken
      but fail to acknowledge adequately the heterogeneity of migrant women. The paper
      provides a definition of the concept as a descriptive theory and argues that
      research must include a clear definition of the migrant specific demographics of
      the women. This should include country/region of origin and host, status within
      the legal system of host country, type of migration experience, and length of
      residence. CONCLUSION: There is a need for a more systematic conceptualization of
      the idea of migrant women within European literature related to pregnancy
      experiences and outcomes to reflect the heterogeneity of this concept. To this
      end, the schema suggested in this paper should be adopted in future research.

PMID- 29052922
TI  - Many patients labelled as having mild asthma do not have well-controlled asthma.

PMID- 29052923
TI  - Hexagonal Sphericon Hematite with High Performance for Water Oxidation.
AB  - A cost-effective hexagonal sphericon hematite with predominant (110) facets for
      the oxygen evolution reaction (OER) is demonstrated. Sequential incorporation of
      near-atomic uniformly distributed Ce species and Ni nanoparticles into selected
      sites of the hematite induces a complex synergistic integration phenomenon that
      enhances the overall catalytic OER performance. This cheap hexagonal sphericon
      hematite (Fe ~ 98%) only needs a small overpotential (eta) of 0.34 V to reach 10
      mA cm-2 , superior to commercial IrO2 and more expensive Co-, Ni-, and Li-based
      electrocatalysts.

PMID- 29052924
TI  - MERS, SARS and other coronaviruses as causes of pneumonia.
AB  - Human coronaviruses (HCoVs) have been considered to be relatively harmless
      respiratory pathogens in the past. However, after the outbreak of the severe
      acute respiratory syndrome (SARS) and emergence of the Middle East respiratory
      syndrome (MERS), HCoVs have received worldwide attention as important pathogens
      in respiratory tract infection. This review focuses on the epidemiology,
      pathogenesis and clinical characteristics among SARS-coronaviruses (CoV), MERS
      CoV and other HCoV infections.

PMID- 29052926
TI  - Platinum-Based Nanowires as Active Catalysts toward Oxygen Reduction Reaction: In
      Situ Observation of Surface-Diffusion-Assisted, Solid-State Oriented Attachment.
AB  - Facile fabrication of advanced catalysts toward oxygen reduction reaction with
      improving activity and stability is significant for proton-exchange membrane fuel
      cells. Based on a generic solid-state reaction, this study reports a modified
      hydrogen-assisted, gas-phase synthesis for facile, scalable production of
      surfactant-free, thin, platinum-based nanowire-network electrocatalysts. The free
      standing platinum and platinum-nickel alloy nanowires show improvements of up to
      5.1 times and 10.9 times for mass activity with a minimum 2.6% loss after an
      accelerated durability test for 10k cycles; 8.5 times and 13.8 times for specific
      activity, respectively, compared to commercial Pt/C catalyst. In addition,
      combined with a wet impregnation method, different substrate-materials-supported
      platinum-based nanowires are obtained, which paves the way to practical
      application as a next-generation supported catalyst to replace Pt/C. The growth
      stages and formation mechanism are investigated by an in situ transmission
      electron microscopy study. It reveals that the free-standing platinum nanowires
      form in the solid state via metal-surface-diffusion-assisted oriented attachment
      of individual nanoparticles, and the interaction with gas molecules plays a
      critical role, which may represent a gas-molecular-adsorbate-modified growth in
      catalyst preparation.

PMID- 29052925
TI  - Structural insights into natural compounds as inhibitors of Fasciola gigantica
      thioredoxin glutathione reductase.
AB  - Fascioliasis is caused by the helminth parasites of genus Fasciola. Thioredoxin
      glutathione reductase (TGR) is an important enzyme in parasitic helminths and
      plays an indispensable role in its redox biology. In the present study, we
      conducted a structure-based virtual screening of natural compounds against the
      Fasciola gigantica TGR (FgTGR). The compounds were docked against FgTGR in four
      sequential docking modes. The screened ligands were further assessed for Lipinski
      and ADMET prediction so as to evaluate drug proficiency and likeness property.
      After refinement, three potential inhibitors were identified that were subjected
      to 50 ns molecular dynamics simulation and free energy binding analyses to
      evaluate the dynamics of protein-ligand interaction and the stability of the
      complexes. Key residues involved in the interaction of the selected ligands were
      also determined. The results suggested that three top hits had a negative binding
      energy greater than GSSG (-91.479 KJ . mol-1 ), having -152.657, -141.219, and 
      92.931 kJ . mol-1 for compounds with IDs ZINC85878789, ZINC85879991, and
      ZINC36369921, respectively. Further analysis showed that the compound
      ZINC85878789 and ZINC85879991 displayed substantial pharmacological and
      structural properties to be a drug candidate. Thus, the present study might prove
      useful for the future design of new derivatives with higher potency and
      specificity.

PMID- 29052927
TI  - Jejuno-jejunal intussusception following gastrectomy.

PMID- 29052928
TI  - Relationship between physical activity levels and depressive symptoms in
      community-dwelling older Japanese adults.
AB  - AIM: The aim of the present study was to investigate the relationship between
      physical activity (PA) and depressive symptoms in community-dwelling older
      Japanese adults. METHODS: A cross-sectional study design was used to obtain data
      from 3191 community-dwelling older Japanese adults aged 70-95 years. Depressive
      symptoms were assessed using self-reported scores on the Geriatric Depression
      Scale-15. PA was objectively measured using an accelerometer worn for a maximum
      of 40 days, and average daily durations of light-intensity PA (LPA), moderate-to
      vigorous intensity PA (MVPA) and step count were calculated. PA was compared
      between participants with and without depressive symptoms by carrying out
      analysis of covariance and multivariable logistic regression analysis adjusted
      for all covariates by using propensity scores. RESULTS: Depressive symptoms were
      present in 598 participants (19.6%). A comparison of propensity-score adjusted PA
      showed that step count (5059.6 +/- 53.7 vs 5003.0 +/- 112.1 count/day; P = 0.652)
      and moderate-to-vigorous intensity PA duration (23.0 +/- 0.4 vs 23.8 +/- 0.7
      min/day; P = 0.358) were not significantly different between participants with
      and without depressive symptoms, respectively. However, participants without
      depressive symptoms had a significantly higher LPA duration than those with
      depressive symptoms (39.4 +/- 0.3 vs 37.3 +/- 0.7 min/day, respectively; P <
      0.01). CONCLUSIONS: The present results suggest that individuals with lower LPA
      have a higher risk of depressive symptoms. These findings imply that PA
      recommendations, especially for older adults, should emphasize LPA, which appears
      to be especially effective at preventing depressive symptoms. Geriatr Gerontol
      Int 2018; 18: 421-427.

PMID- 29052929
TI  - What makes generalist mental health professionals effective when working with
      people with an intellectual disability? A family member and support person
      perspective.
AB  - BACKGROUND: Generalist mental health professionals are inadequately equipped to
      meet the rights of people with intellectual disability. A better understanding of
      the attributes of effective professionals may assist in the development of
      workforce capacity in this area. METHODS: Twenty-eight family/support persons of
      people with intellectual disability participated in four focus groups. Thematic
      analysis was undertaken applying the Intellectual Disability Mental Health Core
      Competencies Framework. RESULTS: Participants described attributes that aligned
      with current professional expectations such as working together and new
      attributes such as differentiating between behaviour and mental health. An
      unexpected finding was the need for professionals to be able to infer meaning by
      interpreting multiple sources of information. Participants also wanted
      professionals to acknowledge their professional limitations and seek professional
      support. CONCLUSION: Family/support persons identified a range of attributes of
      effective mental health professionals to support people with intellectual
      disability. Further research is necessary, particularly from the perspective of
      people with intellectual disability.

PMID- 29052931
TI  - Far-red light promotes biofilm formation in the cyanobacterium Acaryochloris
      marina.
AB  - Light quantity and quality promotes ecological-niche differentiation of
      photosynthetic organisms. The existence of cyanobacteria capable of performing
      photosynthesis using red-shifted chlorophylls, chlorophyll d and f, reduces
      competition between species in light-limiting environments, and permits them to
      thrive in niches enriched in far-red light. We examined global transcriptome
      changes due to changing the culture light conditions in Acaryochloris marina, a
      chlorophyll d-containing cyanobacterium. We identified the functional category of
      'photosynthesis' as the most down-regulated and the category of 'cell
      wall/membrane biogenesis' as the most up-regulated through a functional
      enrichment analysis of genes differentially expressed. Within the category of
      'cell wall/membrane biogenesis', genes encoding glycosysltransferases accumulated
      the most in response to far-red light. Further experimental results confirmed
      that cells grown under far-red light form biofilms with a significantly increased
      adherence compared to cells grown under white light. Taken together, these
      results indicate that Acaryochloris marina shifts its lifestyle from a planktonic
      state under white light to an immobilized state under far-red light.

PMID- 29052930
TI  - Comprehensive functional characterization of the glycoside hydrolase family 3
      enzymes from Cellvibrio japonicus reveals unique metabolic roles in biomass
      saccharification.
AB  - Lignocellulose degradation is central to the carbon cycle and renewable
      biotechnologies. The xyloglucan (XyG), beta(1->3)/beta(1->4) mixed-linkage glucan
      (MLG) and beta(1->3) glucan components of lignocellulose represent significant
      carbohydrate energy sources for saprophytic microorganisms. The bacterium
      Cellvibrio japonicus has a robust capacity for plant polysaccharide degradation,
      due to a genome encoding a large contingent of Carbohydrate-Active enZymes
      (CAZymes), many of whose specific functions remain unknown. Using a comprehensive
      genetic and biochemical approach, we have delineated the physiological roles of
      the four C. japonicus glycoside hydrolase family 3 (GH3) members on diverse beta
      glucans. Despite high protein sequence similarity and partially overlapping
      activity profiles on disaccharides, these beta-glucosidases are not functionally
      equivalent. Bgl3A has a major role in MLG and sophorose utilization, and supports
      beta(1->3) glucan utilization, while Bgl3B underpins cellulose utilization and
      supports MLG utilization. Bgl3C drives beta(1->3) glucan utilization. Finally,
      Bgl3D is the crucial beta-glucosidase for XyG utilization. This study not only
      sheds the light on the metabolic machinery of C. japonicus, but also expands the
      repertoire of characterized CAZymes for future deployment in biotechnological
      applications. In particular, the precise functional analysis provided here serves
      as a reference for informed bioinformatics on the genomes of other Cellvibrio and
      related species.

PMID- 29052933
TI  - Traumatic fracture dislocation of the thoracic spine sparing both the spinal cord
      and aorta.

PMID- 29052932
TI  - Preparation of Functionalized Diaryl- and Diheteroaryllanthanum Reagents by Fast
      Halogen-Lanthanum Exchange.
AB  - Aryl and heteroaryl halides (X=Br, I) undergo a fast and convenient halogen
      lanthanum exchange with nBu2 LaMe, which leads to functionalized diaryl- and
      diheteroaryllanthanum derivatives. Subsequent trapping reactions with selected
      electrophiles, such as ketones, aldehydes, or amides, proceeded smoothly at -50 
      degrees C in THF, affording polyfunctionalized alcohols and carbonyl derivatives.
      Kinetic competition experiments revealed a similar reactivity trend as for Br/Mg
      exchange, but 106 -times higher rates, making it comparable to Br/Li exchange.

PMID- 29052934
TI  - The contribution of alternative splicing to genetic risk for psychiatric
      disorders.
AB  - A genetic contribution to psychiatric disorders has clearly been established and
      genome-wide association studies now provide the location of risk genes and
      genetic variants associated with risk. However, the mechanism by which these
      genes and variants contribute to psychiatric disorders is mostly undetermined.
      This is in part because non-synonymous protein coding changes cannot explain the
      majority of variants associated with complex genetic traits. Based on this, it is
      predicted that these variants are causing gene expression changes, including
      changes to alternative splicing. Genetic changes influencing alternative splicing
      have been identified as risk factors in Mendelian disorders; however, currently
      there is a paucity of research on the role of alternative splicing in complex
      traits. This stems partly from the difficulty of predicting the role of genetic
      variation in splicing. Alterations to canonical splice site sequences,
      nucleotides adjacent to splice junctions, and exonic and intronic splicing
      regulatory sequences can influence splice site choice. Recent studies have
      identified global changes in alternatively spliced transcripts in brain tissues,
      some of which correlate with altered levels of splicing trans factors. Disease
      associated variants have also been found to affect cis-acting splicing regulatory
      sequences and alter the ratio of alternatively spliced transcripts. These
      findings are reviewed here, as well as the current datasets and resources
      available to study alternative splicing in psychiatric disorders. Identifying and
      understanding risk variants that cause alternative splicing is critical to
      understanding the mechanisms of risk as well as to pave the way for new
      therapeutic options.

PMID- 29052935
TI  - Relationship between chronic kidney disease without diabetes mellitus and
      components of frailty in community-dwelling Japanese older adults.
AB  - AIM: To evaluate the relationship between kidney function without diabetes and
      components of the frailty phenotype in community-dwelling Japanese older adults.
      METHODS: Participants were 8343 residents who completed baseline assessments,
      classified into four categories according to eGFR. Frailty status was defined
      using five criteria: (i) slow gait speed; (ii) muscle weakness; (iii) low
      physical activity; (iv) exhaustion; and (v) unintentional weight loss. RESULTS:
      After multivariate adjustment, participants with the lowest kidney function were
      at higher risk of frailty (OR 1.57, 95% CI 1.02-3.50) than those with normal
      kidney function. In addition, after adjustment for multiple confounders,
      estimated glomerular filtration rate <30 was associated with a greater risk of
      the individual frailty components of weight loss (OR 2.14, 95% CI 1.11-4.12), low
      physical activity (OR 1.35, 95% CI, 1.01-2.54) and slowness (OR 1.82, 95% CI 1.36
      3.77) compared with estimated glomerular filtration rate >=60. CONCLUSIONS: Lower
      kidney function was associated with a higher risk of weight loss, low physical
      activity and slowness among community-dwelling Japanese older adults. Geriatr
      Gerontol Int 2018; 18: 286-292.

PMID- 29052936
TI  - A humanized monoclonal antibody that inhibits platelet-surface ERp72 reveals a
      role for ERp72 in thrombosis.
AB  - : Essentials ERp72 is a thiol isomerase enzyme. ERp72 levels increase at the
      platelet surface during platelet activation. We generated a humanized monoclonal
      antibody which blocks ERp72 enzyme activity (anti-ERp72). Anti-ERp72 inhibits
      platelet functional responses and thrombosis. SUMMARY: Background Within the
      endoplasmic reticulum, thiol isomerase enzymes modulate the formation and
      rearrangement of disulfide bonds in newly folded proteins entering the secretory
      pathway to ensure correct protein folding. In addition to their intracellular
      importance, thiol isomerases have been recently identified to be present on the
      surface of a number of cell types where they are important for cell function.
      Several thiol isomerases are known to be present on the resting platelet surface,
      including PDI, ERp5 and ERp57, and levels are increased following platelet
      activation. Inhibition of the catalytic activity of these enzymes results in
      diminished platelet function and thrombosis. Aim We previously determined that
      ERp72 is present at the resting platelet surface and levels increase upon
      platelet activation; however, its functional role on the cell surface was
      unclear. We aimed to investigate the role of ERp72 in platelet function and its
      role in thrombosis. Methods Using HuCAL technology, fully humanized Fc-null anti
      ERp72 antibodies were generated. Eleven antibodies were screened for their
      ability to inhibit ERp72 activity and the most potent inhibitory antibody (anti
      ERp72) selected for further testing in platelet functional assays. Results and
      conclusions Anti-ERp72 inhibited platelet aggregation, granule secretion, calcium
      mobilisation and integrin activation, revealing an important role for
      extracellular ERp72 in the regulation of platelet activation. Consistent with
      this, infusion of anti-ERp72 into mice protected against thrombosis.

PMID- 29052937
TI  - Targeting of C-type lectin-like receptor 2 or P2Y12 for the prevention of
      platelet activation by immunotherapeutic CpG oligodeoxynucleotides: comment.

PMID- 29052938
TI  - When is a complication a complication in contemporary cataract surgery?

PMID- 29052940
TI  - Outcomes of percutaneous cholecystostomy and predictors of subsequent
      cholecystectomy.
AB  - BACKGROUND: The use of a percutaneous cholecystostomy (PC) in the management of
      severe acute cholecystitis is a well recognized alternative to acute
      cholecystectomy. The need for definitive surgical management remains
      controversial. METHODS: A retrospective analysis of hospital records at Nambour
      General Hospital between 2012 and 2016 was conducted and data relating to
      indications, demographics, comorbidities and outcomes were collected. RESULTS:
      Thirty PC patients (20 male and 10 female) were identified, with a mean age of 77
      years (range 46-93). Thirteen proceeded to cholecystectomy, nine elective and
      four emergent. Mean time to operation was 97 days (range 1-480). Ten were
      performed laparoscopically with a complication rate of 23% (3/13). One patient in
      the operative group died. Seventeen patients did not proceed to cholecystectomy.
      Fifteen resolved and were discharged, and two died. Three of those discharged
      were readmitted with gallstone disease requiring treatment, one of which died. A
      total of 71% (12/17) of the non-operative group died and three of those had a
      cause of death related to gallstone disease. The operative group was younger (P =
      0.01) and had a lower estimated mortality risk (P < 0.05). In this cohort, this
      translated to an overall survival benefit (P < 0.01). CONCLUSION: Predictors of
      eventual cholecystectomy include younger age and lower estimated mortality risk.
      Patients who require a PC for the treatment of acute cholecystitis and
      subsequently go on to cholecystectomy can expect to have a favourable outcome.

PMID- 29052941
TI  - A method for extracting carboxy-myoglobin from beef.
AB  - The present study was conducted to devise a method for the effective extraction
      of carboxy-myoglobin (COMb) from beef without carbon monoxide dissociation. The
      ratio of COMb to myoglobin was computed at absorptions of wavelengths 541 and 551
      nm, which characterize COMb and the isosbestic point between COMb and deoxy
      myoglobin, respectively. The COMb extraction rate was found to vary with
      temperature, pH and oxygen conditions. The decrease observed in this rate was
      inversely proportional to the rise in extraction temperature. The COMb extraction
      rate was also affected by pH, and the stability of COMb in the extract solution
      was the highest at pH 8.0-9.0. Moreover, the presence of oxygen was found to
      disturb COMb extraction. According to these results, nearly all COMb could be
      extracted from carbon-monoxide-treated beef under stirring conditions in pH 8.5
      deoxidized buffer, at 1 degrees C, and under N2 flow with the improved extraction
      method in this study (98.1 +/- 2.7%). The decrement of COMb in the extract was
      accelerated by light, and the COMb was stable for 20 min in the dark, at 1
      degrees C. The extraction conditions for COMb described above should allow the
      accurate evaluation of COMb in meat tissue.

PMID- 29052939
TI  - Quantitative trait locus mapping and analysis of heritable variation in
      affiliative social behavior and co-occurring traits.
AB  - Humans exhibit broad heterogeneity in affiliative social behavior. Twin and
      family studies show that individual differences in core dimensions of social
      behavior are heritable, yet there are knowledge gaps in understanding the
      underlying genetic and neurobiological mechanisms. Animal genetic reference
      panels (GRPs) provide a tractable strategy for examining the behavioral and
      genetic architecture of complex traits. Here, using males from 50 mouse strains
      from the BXD GRP, 4 domains of affiliative social behavior-social approach,
      social recognition, direct social interaction (DSI) (partner sniffing) and vocal
      communication-were examined in 2 widely used behavioral tasks-the 3-chamber and
      DSI tasks. There was continuous and broad variation in social and nonsocial
      traits, with moderate to high heritability of social approach sniff preference
      (0.31), ultrasonic vocalization (USV) count (0.39), partner sniffing (0.51),
      locomotor activity (0.54-0.66) and anxiety-like behavior (0.36). Principal
      component analysis shows that variation in social and nonsocial traits are
      attributable to 5 independent factors. Genome-wide mapping identified significant
      quantitative trait loci for USV count on chromosome (Chr) 18 and locomotor
      activity on Chr X, with suggestive loci and candidate quantitative trait genes
      identified for all traits with one notable exception-partner sniffing in the DSI
      task. The results show heritable variation in sociability, which is independent
      of variation in activity and anxiety-like traits. In addition, a highly heritable
      and ethological domain of affiliative sociability-partner sniffing-appears highly
      polygenic. These findings establish a basis for identifying functional natural
      variants, leading to a new understanding typical and atypical sociability.

PMID- 29052942
TI  - Genealogies of recovery: The framing of therapeutic ambitions.
AB  - The notion of recovery has become prominent in mental healthcare discourse in the
      UK, but it is often considered as if it were a relatively novel notion, and as if
      it represented an alternative to conventional treatment and intervention. In this
      paper, we explore some of the origins of the notion of recovery in the early 20th
      century in movements such as Alcoholics Anonymous and Recovery Inc. Whilst these
      phenomena are not entirely continuous with recovery in the present day, some
      important antecedents of the contemporary notion can be detected. These include
      the focus on the sufferers' interior space as a key theatre of operations and the
      reinforcement and consolidation of medical ways of seeing the condition without
      any immediate medical supervision of the actors being necessary. This has
      resonance with many contemporary examples of recovery in practice where the art
      of living with a mental health condition is emphasised without the nature of the
      psychopathological condition itself being challenged.

PMID- 29052943
TI  - Towards a capability approach to child growth: A theoretical framework.
AB  - Child malnutrition is an important cause of under-5 mortality and morbidity
      around the globe. Despite the partial success of (inter)national efforts to
      reduce child mortality, under-5 mortality rates continue to be high. The
      multidimensional approaches of the Sustainable Development Goals may suggest new
      directions for rethinking strategies for reducing child mortality and
      malnutrition. We propose a theoretical framework for developing a "capability"
      approach to child growth. The current child growth monitoring practices are based
      on 2 assumptions: (a) that anthropometric and motor development measures are the
      appropriate indicators; and (b) that child growth can be assessed using a single
      universal standard that is applicable around the world. These practices may be
      further advanced by applying a capability approach to child growth, whereby
      growth is redefined as the achievement of certain capabilities (of society,
      parents, and children). This framework is similar to the multidimensional
      approach to societal development presented in the seminal work of Amartya Sen. To
      identify the dimensions of healthy child growth, we draw upon theories from the
      social sciences and evolutionary biology. Conceptually, we consider growth as a
      plural space and propose assessing growth by means of a child growth matrix in
      which the context is embedded in the assessment. This approach will better
      address the diversities and the inequalities in child growth. Such a
      multidimensional measure will have implications for interventions and policy,
      including prevention and counselling, and could have an impact on child
      malnutrition and mortality.

PMID- 29052944
TI  - Differential expression of the three Alcanivorax borkumensis SK2 genes coding for
      the P450 cytochromes involved in the assimilation of hydrocarbons.
AB  - Alcanivorax borkumensis, a marine bacterium highly specialized in degrading
      linear and branched alkanes, plays a key ecological role in the removal of marine
      oil spills. It contains several alternative enzyme systems for terminal
      hydroxylation of alkanes, including three P450 cytochromes (P450-1, P450-2 and
      P450-3). The present work shows cytochrome P450-1 to be expressed from the
      promoter of the upstream gene fdx. Promoter Pfdx was more active when C8 -C18 n
      alkanes or pristane were assimilated than when pyruvate was available. The
      product of ABO_0199 (named CypR) was identified as a transcriptional activator of
      Pfdx . The inactivation of cypR impaired growth on tetradecane, showing the
      importance of the fdx-P450-1 and/or cypR genes. P450-2 expression was low-level
      and constitutive under all conditions tested, while that of P450-3 from promoter
      P450-3 was much higher when cells assimilated pristane than when n-alkanes or
      pyruvate were available. However, the inactivation of P450-3 had no visible
      impact on pristane assimilation. Cyo terminal oxidase, a component of the
      electron transport chain, was found to stimulate promoter PP450-3 activity, but
      it did not affect promoters Pfdx or PP450-2 . A. borkumensis, therefore, appears
      to carefully coordinate the expression of its multiple hydrocarbon degradation
      genes using both specific and global regulatory systems.

PMID- 29052945
TI  - Design, synthesis, and cytotoxic evaluation of novel scopoletin derivatives.
AB  - A series of scopoletin derivatives were designed and synthesized by introducing
      alpha-aminoacetamide, acrylamide and beta-aminopropamide, respectively, to 3
      position of scopoletin, and their chemical structures were confirmed by ESI-MS,
      IR, 1 H NMR, and 13 C NMR spectra. All target compounds were evaluated in vitro
      against four human cancer cell lines (MDA-MB-231, MCF-7, HepG2, and A549) by MTT
      method. Cytotoxic assay showed that compounds 7a, 7b, 7e, 7f, 8a, and 8e
      exhibited more potent cytotoxicities compared to scopoletin. Besides, we have
      further evaluated the growth inhibitory activities of these selected compounds
      against normal tissue cell lines HFL-1. Although compound 8a showed the strongest
      antiproliferative activity in vitro, it exhibited strong cytotoxicity on normal
      cells HFL-1, which limited its further study. Compound 7a and 7b exhibited higher
      antiproliferative activity against MDA-MB-231 and HepG2 cells and weak
      cytotoxicity on HFL-1, which suggested that 7a and 7b might be ideal anticancer
      candidates. The SARs showed that the introduction of the acrylamide and its
      analogues beta-aminopropamide could significantly improve activity, while the
      alpha-aminoacetamide failed to enhance potency obviously. Therefore, the
      mechanism of compound 7a and 7b is worthy of further research and the structure
      of compound 8a should be further optimized.

PMID- 29052946
TI  - Hierarchical evaluation of electrical stimulation protocols for chronic wound
      healing: An effect size meta-analysis.
AB  - Electrical stimulation (ES) has been tested for decades to improve chronic wound
      healing. However, uncertainty remains on the magnitude of the efficacy and on the
      best applicable protocol. We conducted an effect size meta-analysis to assess the
      overall efficacy of ES on wound healing, to compare the efficacy of the different
      modalities of electrical stimulation, and to determine whether efficacy differs
      depending on the wound etiology, size, and age of the chronic wound. Twenty-nine
      randomized clinical trials with 1,510 patients and 1,753 ulcers were selected.
      Overall efficacy of ES on would healing was a 0.72 SMD (95% CI: 0.48, 1)
      corresponding to a moderate to large effect size. We found that unidirectional
      high voltage pulsed current (HVPC) with the active electrode over the wound was
      the best evidence-based protocol to improve wound healing with a 0.8 SMD (95% CI:
      0.38, 1.21), while evaluation of the efficacy of direct current was limited by
      the small number of studies. ES was more effective on pressure ulcers compared to
      venous and diabetic ulcers, and efficacy trended to be inversely associated with
      the wound size and duration. This study confirms the overall efficacy of ES to
      enhance healing of chronic wounds and highlights the superiority of HVPC over
      other type of currents, which is more effective on pressure ulcers, and inversely
      associated with the wound size and duration. This will enable to standardize
      future ES practices.

PMID- 29052947
TI  - Exploring opportunities to support mental health care using social media: A
      survey of social media users with mental illness.
AB  - AIM: Social media holds promise for expanding the reach of mental health
      services, especially for young people who frequently use these popular platforms.
      We surveyed social media users who self-identified as having a mental illness to
      learn about their use of social media for mental health and to identify
      opportunities to augment existing mental health services. METHODS: We asked 240
      Twitter users who self-identified in their profile as having a mental illness to
      participate in an online survey. The survey was in English and inquired about
      participants' mental health condition, use of social media for mental health and
      interest in accessing mental health programs delivered through social media.
      RESULTS: Respondents from 10 countries completed 135 surveys. Most respondents
      were from the United States (54%), Canada (22%) and the United Kingdom (17%) and
      reported a psychiatric diagnosis of either schizophrenia spectrum disorder (27%),
      bipolar disorder (25%), major depressive disorder (16%) or depression (20%).
      Young adults age <=35 (46%) were more likely to use Instagram (P = .002),
      Snapchat (P < .001) and their mobile phone for accessing social media (P < .001)
      compared to adults age 36 and older (53%). Most participants (85%) expressed
      interest in mental health programs delivered through social media, especially to
      promote overall health and wellbeing (72%) and for coping with mental health
      symptoms (90%). CONCLUSIONS: This exploratory study demonstrates the feasibility
      of reaching social media users with mental illness and can inform efforts to
      leverage social media to make evidence-based mental health services more widely
      available to those in need.

PMID- 29052948
TI  - Association of participant preferences on work and school participation after a
      first episode of psychosis.
AB  - AIM: To explore baseline ratings of importance (ROI) across life domains for
      participants in the Recovery After an Initial Schizophrenia Episode Connection
      Program (RAISE CP), and investigate whether ratings were correlated with
      intervention outcomes over time. METHODS: At baseline, 63 participants rated the
      importance of reducing symptoms, side-effects, confusion, increasing energy and
      school/work functioning and improving social relations. ROIs were examined in
      relation to work/school participation (n = 41) and occupational functioning (n =
      37) after 12 months. Participants' mean age was 22.3 (+/-4.2). RESULTS: The ROI
      domain rated as most important was school/work functioning, and higher
      school/work ROI at baseline predicted work/school participation after 12 months
      of participation. CONCLUSIONS: It is particularly important to assess participant
      preferences and priorities when treating psychotic disorders because most areas
      of life are affected. Understanding the impact of participant goals on outcomes
      is essential as programs design patient-centred treatment plans.

PMID- 29052950
TI  - Erratum.

PMID- 29052949
TI  - The risks and external effects of diabetic foot ulcer on diabetic patients: A
      hospital-based survey in Wuhan area, China.
AB  - Diabetic foot ulcer (DFU) is a common complication observed in diabetic patients
      and affects diabetic patients in multiple ways. Severe DFU even leads to
      amputation in many cases. Early detection and intervention of DFU in diabetic
      patients can significantly relieve the pain caused by the ulcer and also keep
      patients from losing limbs in severe cases. In this study, the risks of diabetic
      patients getting DFU were estimated through a hospital-based survey. This survey
      collected information from hospitalized diabetic patients in Wuhan City, Hubei
      Province, China, using a questionnaire. This investigation includes studies from
      two stages with 502 diabetic patients from 20 hospitals in Wuhan City. The
      results suggested that patients with a long history of diabetes are often
      associated with a high risk of DFU (chi2  = 11.428, p = 0.0007), smoking (chi2  =
      8.386, p = 0.0007), diabetic complications (chi2  = 13.484, p < 0.0001), and
      especially patients with diabetic foot complications (chi2  = 57.6621, p <
      0.0001). Foot lesions appeared to be important attributors to DFU since our data
      demonstrated close correlations between DFU and patients with calluses/corns
      (chi2  = 4.584, p = 0.0323), tinea pedis (chi2  = 4.030, p = 0.0447), and cracked
      skin (chi2  = 8.712, p = 0.0032). Only a small number of patients seek for the
      assistance from specialists, such as trimming toenails (3.4%), removing corn or
      calluses (1.4%) or treating wounds (11.78%), when they are suffering from foot
      problems. The findings of this study can potentially be utilized to develop an
      early DFU diagnostic method in diabetic patients and can provide objective
      evidence for suggesting that patients who are suffering from foot problems should
      seek professional help.

PMID- 29052951
TI  - Basic self-disturbance, neurocognition and metacognition: A pilot study among
      help-seeking adolescents with and without attenuated psychosis syndrome.
AB  - AIM: The goal of this pilot study was to assess the association between basic
      self-disturbance (SD) and deficits in neurocognitive and metacognitive
      functioning among help-seeking adolescents with and without attenuated psychosis
      syndrome (APS). METHODS: Sixty-one non-psychotic, help-seeking adolescents (age
      13-18) were assessed with the examination of anomalous self-experience, the
      structured interview for prodromal syndromes and a new metacognitive approach to
      neurocognitive assessment applied to two non-social (executive functions and
      verbal memory) and two social (theory of mind and emotion recognition) domains.
      After each answer, subjects were also requested to indicate their level of
      confidence in the answer and to decide whether they desired it to be "counted"
      toward their total score on the task. Each volunteered answer earned a 5-cent
      gain if correct, but an equal fine if wrong. RESULTS: As hypothesized,
      metacognitive monitoring and control had a significant contribution to the
      prediction of SD over and above neurocognitive functioning and attenuated
      psychotic symptoms. However, the direction of this association was positive
      rather than negative. Also, inconsistent with or hypothesis, it was not moderated
      by the presence of APS. CONCLUSIONS: These pilot results provide preliminary
      support a modest association between SD and metacognition, which is not reducible
      to neurocognition and APS. In addition, they raise an intriguing possibility
      regarding metacognitive monitoring and control being indicators of hyper
      reflectivity that characterizes individuals with SD. However, further research
      with larger samples and high-stress assessment conditions are needed to assess
      this possibility.

PMID- 29052952
TI  - Factor structure of the Cannabis Experiences Questionnaire in a first-episode
      psychosis sample.
AB  - AIM: The Cannabis Experiences Questionnaire (CEQ) was developed to measure the
      subjective experiences of cannabis use both during and after intoxication.
      Despite the need to better understand the nature of the complex and significant
      relationship between cannabis use and early psychosis, this questionnaire has
      rarely been used in individuals with first-episode psychosis. METHODS: We
      conducted a set of factor analyses using CEQ data from 194 first-episode
      psychosis patients who used cannabis in order to uncover the underlying factor
      structure of the questionnaire and thus the overarching types of psychological
      experiences during/after using cannabis in young people with psychotic disorders.
      RESULTS: Our exploratory factor analysis identified 4 subscales, including:
      Distortions of Reality and Self-Perception (Factor 1), Euphoria Effects (Factor
      2), Slowing and Amotivational Effects (Factor 3), and Anxiety and Paranoia
      Effects (Factor 4). CONCLUSIONS: Elucidating the underlying factor structure of
      the CEQ in first-episode psychosis samples could help researchers move towards a
      deeper understanding of the types of experiences associated with cannabis
      intoxication among young adults with first-episode psychosis and could inform the
      development of programs designed to reduce use, improve the course of illness,
      and possibly delay or prevent the onset of psychotic symptoms in those at risk.

PMID- 29052953
TI  - Cross-cultural adaptation and validation of the Comprehensive Frailty Assessment
      Instrument in Chinese community-dwelling older adults.
AB  - AIM: To cross-culturally adapt and validate the Comprehensive Frailty Assessment
      Instrument (CFAI) among Chinese community-dwelling older adults. METHODS: The
      Chinese CFAI was developed through forward-backward translations. An urban sample
      of 1235 community-dwelling older adults received face-to-face interviews to
      examine the validity (construct validity and criterion validity) and reliability
      (internal consistency and test-retest reliability). RESULTS: The Chinese CFAI
      achieved semantic and idiomatic equivalence, and showed acceptable reliability
      and an expected factor structure, except for the social support domain. The
      exploratory factor analysis extracted five factors explaining 53.8% of the total
      variance of frailty. The confirmatory factor analysis showed that the data fit
      well to the second-order factor theoretical model, with a root mean square error
      of approximation of 0.05, Tucker-Lewis Index of 0.93 and Comparative Fit Index of
      0.95. The receiver operating characteristic analysis presented an acceptable
      criterion validity using the Rockwood Frailty Index as an external criterion
      (area under the curve 0.80), with balanced sensitivity (65.31%) and specificity
      (81.19%) at the optimal 39-point frailty cut-off of the CFAI. CONCLUSIONS: The
      Chinese CFAI has good validity and reliability as a practical frailty measure in
      Chinese community-dwelling older adults. Geriatr Gerontol Int 2018; 18: 301-307.

PMID- 29052954
TI  - Enlarged perivascular spaces are associated with health-related quality of life
      in patients with acute ischemic stroke.
AB  - AIMS: This study explored the association between enlarged perivascular spaces
      (EPVS) and the health-related quality of life (HRQoL) in patients with acute
      ischemic stroke. METHODS: This was an observational study of consecutively
      screened patients with acute ischemic stroke from March 2010 to March 2015. EPVS
      were rated in the basal ganglia and the centrum semiovale with a validated scale.
      The HRQoL was assessed 3 months after the stroke onset using the Stroke-Specific
      Quality of Life (SSQoL). Linear regression models were used to study the
      association between EPVS and HRQoL. RESULTS: The study included 648 patients
      (mean age 65.8 years; 40.0% women) with mild to moderately severe stroke (median
      NIHSS score 2), of whom 640 (98.8%) exhibited signs of small vessel disease. The
      median EPVS scores in the basal ganglia and the centrum semiovale were 1 each. In
      linear regression analysis, EPVS in the basal ganglia were associated with a
      lower total SSQoL score (P = 0.02) and lower mobility (P = 0.01), mood (P =
      0.03), and self-care (P < 0.01). EPVS in the centrum semiovale were associated
      only with a lower SSQoL work/productivity subscore (P = 0.002). CONCLUSIONS: EPVS
      are associated with lower HRQoL in patients with mild to moderate acute ischemic
      stroke. Early identification and intervention of EPVS may improve HRQoL in stroke
      survivors.

PMID- 29052955
TI  - Factors associated with the introduction of complementary feeding in the French
      ELFE cohort study.
AB  - The objectives of this study were to estimate the age of complementary feeding
      introduction (CFI) and investigate the related health, demographic, and socio
      economic factors. Analyses were based on 10,931 infants from the French national
      birth cohort ELFE, born in 2011. Health, demographic, and socio-economic data
      concerning infants and parents were collected at birth (face-to-face interviews
      and medical records) and 2 months (telephone interviews). Data on milk feeding
      and CFI practices were collected at birth and 2 months then monthly from 3 to 10
      months using online or paper questionnaires. The associations between both health
      and social factors and CFI age were tested by multivariable multinomial logistic
      regressions. The mean CFI age was 5.2 +/- 1.2 months; 26% of the infants started
      complementary feeding before 4 months of age (CF < 4 months), 62% between 4 and 6
      months of age, and 12% after 6 months of age (CF > 6 months). CF < 4 months was
      more likely when mothers smoked, were overweight/obese, younger (<29 years), and
      used their personal experience as an information source in child caregiving and
      when both parents were not born in France. CF < 4 months was less likely when the
      infant was a girl, second-born, when the mother breastfed longer, and had
      attended at least one birth preparation class. Mothers of second-born infants and
      who breastfed their child longer were more likely to introduce CF > 6 months.
      Couples in which fathers were born in France and mothers were not born in France
      were less likely to introduce CF > 6 months. CF < 4 months occurred in more than
      25% of the cases. It is important to continue promoting clear CFI
      recommendations, especially in smoking, overweight, young, not born in France,
      and nonbreastfeeding mothers.

PMID- 29052956
TI  - Meta-analysis of full ROC curves using bivariate time-to-event models for
      interval-censored data.
AB  - Systematic reviews and meta-analyses are the cornerstones of evidence-based
      medicine and inform treatment, diagnosis, or prevention of individual patients as
      well as policy decisions in health care. Statistical methods for the meta
      analysis of intervention studies are well established today. Meta-analysis for
      diagnostic accuracy trials has also been a vivid research area in recent years,
      which is especially due to the increased complexity of their bivariate outcome of
      sensitivity and specificity. The situation is even more challenging when single
      studies report a full ROC curve with several pairs of sensitivity and
      specificity, each pair for a different threshold. Researchers frequently ignore
      this information and use only 1 pair of sensitivity and specificity from each
      study to arrive at meta-analytic estimates. Although methods to deal with the
      full information have been proposed, they have some disadvantages, eg, the
      numbers or values of thresholds have to be identical across studies, or the
      precise values of thresholds are ignored. We propose an approach for the meta
      analysis of full ROC curves including the information from all thresholds by
      using bivariate time-to-event models for interval-censored data with random
      effects. This approach avoids the problems of previous methods and comes with the
      additional advantage that it allows for various distributions of the underlying
      continuous test values. The results from a small simulation study are given,
      which show that the approach works well in practice. Furthermore, we illustrate
      our new model using an example based on the population-based screening for type 2
      diabetes mellitus.

PMID- 29052957
TI  - Implementing a family-inclusive practice model in youth mental health services in
      Australia.
AB  - AIM: A brief family-inclusive practice model, single session family consultation
      (SSFC), was introduced at 4 youth mental health service sites to determine the
      extent to which the model could be implemented in this context and its
      acceptability as a means of engaging families of young people. METHODS: Within an
      action research paradigm, both quantitative and qualitative measures were used
      for this implementation project with the former reported here. There were 2
      components: (1) evaluation of the experiences of young people and their families
      and (2) evaluation of the extent of implementation of SSFC. Quantitative data
      were analysed descriptively (item scores, range and any changes over time).
      RESULTS: Twenty practitioners who were trained and supported in the use of SSFC
      participated in the 6-month implementation evaluation. In 6 months, 131 SSFC
      sessions were conducted across the 4 sites and the young people and their
      families were very satisfied with sessions (overall mean = 5.2, range = 0-6). Six
      months post-training, there were statistically significant improvements in the
      practitioners' confidence in providing family interventions (mean improvement = 
      0.47 (95% confidence interval (CI) = -0.91, -0.04), P = .035) and familiarity
      with approaches to working with families (mean improvement = -0.61 (95% CI = 
      1.13, -0.10, P = .023). Practitioners perceived significant improvement in
      organizational support for working with families. CONCLUSIONS: SSFC was
      acceptable to clients and their families, was adopted by practitioners and was
      successfully implemented in the participating sites. This suggests that SSFC,
      when appropriately implemented, is useful to engage families in the treatment of
      young people facing mental health issues.

PMID- 29052958
TI  - Whole genome re-sequencing reveals evolutionary patterns of sacred lotus (Nelumbo
      nucifera).
AB  - Sacred lotus (Nelumbo nucifera or lotus) is an important aquatic plant in
      horticulture and ecosystems. As a foundation for exploring genomic variation and
      evolution among different germplasms, we re-sequenced 19 individuals from three
      cultivated temperate lotus subgroups (rhizome, seed and flower lotus), one wild
      temperate lotus subgroup (wild lotus), one tropical lotus group (Thai lotus) and
      an outgroup (Nelumbo lutea). Through genetic diversity and polymorphism analysis
      by non-missing SNP sites widely distributed in the whole genome, we confirmed
      that wild and Thai lotus exhibited greater differentiation with a higher genomic
      diversity compared to cultivated lotus. Rhizome lotus had the lowest genomic
      diversity and a closer relationship to wild lotus, whereas the genomes of seed
      and flower lotus were admixed. Genes in energy metabolism process and plant
      immunity evolved rapidly in lotus, reflecting local adaptation. We established
      that candidate genes in genomic regions with significant differentiation
      associated with temperate and tropical lotus divergence always exhibited highly
      divergent expression pattern. Together, this study comprehensive and credible
      interpretates important patterns of genetic diversity and relationships, gene
      evolution, and genomic signature from ecotypic differentiation of sacred lotus.

PMID- 29052959
TI  - Peptide ligands for targeting the extracellular domain of EGFR: Comparison
      between linear and cyclic peptides.
AB  - Colorectal cancer (CRC) is the third most common solid internal malignancy among
      cancers. Early detection of cancer is key to increasing the survival rate of
      colorectal cancer patients. Overexpression of the EGFR protein is associated with
      CRC. We have designed a series of peptides that are highly specific for the
      extracellular domain of EGFR, based on our earlier studies on linear peptides.
      The previously reported linear peptide LARLLT, known to bind to EGFR, was
      modified with the goals of increasing its stability and its specificity toward
      EGFR. Peptide modifications, including D-amino acid substitution, cyclization,
      and chain reversal, were investigated. In addition, to facilitate labeling of the
      peptide with a fluorescent dye, an additional lysine residue was introduced onto
      the linear (KLARLLT) and cyclic peptides cyclo(KLARLLT) (Cyclo.L1). The lysine
      residue was also converted into an azide group in both a linear and reversed
      cyclic peptide sequences cyclo(K(N3)larllt) (Cyclo.L1.1) to allow for subsequent
      "click" conjugation. The cyclic peptides showed enhanced binding to EGFR by SPR.
      NMR and molecular modeling studies suggest that the peptides acquire a beta-turn
      structure in solution. In vitro stability studies in human serum show that the
      cyclic peptide is more stable than the linear peptide.

PMID- 29052960
TI  - Treatment and outcomes of melanoma in Asia: Results from the National Cancer
      Centre Singapore.
AB  - BACKGROUND: Acral melanoma (AM) and mucosal melanoma (MM) make up more than half
      of melanomas in Asia but comprise only 5% of cases in Caucasians, where cutaneous
      melanoma (CM) predominates. AM and MM are thought to be genetically and
      biologically distinct from CM. We report the characteristics and outcomes of
      melanoma patients from the National Cancer Centre Singapore. METHODS: Case
      records of 210 patients treated between 2002 and 2014 were reviewed. RESULTS:
      Median follow-up was 2.5 years. CM, AM and MM made up of 37.6%, 33.8% and 16.2%
      of cases, respectively, with 6.2% each having ocular melanoma and unknown
      primary. Caucasians made up 16.2% of patients, accounting for 36.7% of CM but
      only 2.8 of AM and 2.9% of MM. Patients with MM (2.9% stage I, 14.7% stage IV)
      presented with higher American Joint Committee on Cancer (AJCC) stage than those
      with AM (16.9% stage I, 5.6% stage IV) or CM (24.1% stage I, 8.9% stage IV) (P =
      0.01). Median overall survival (OS) was 5.7 years for all patients, and 1.0 year
      for metastatic disease. Considering stage I-III disease, multivariable Cox
      regression analysis demonstrated age >=60 years and higher stage to be
      independent adverse prognostic factors for RFS and OS. Sentinel lymph node
      biopsy, undertaken for 56 stage I-III patients (25 AM, 31 CM) did not influence
      outcome. CONCLUSION: Our study reinforces the known unique clinicopathologic
      features of melanomas in Asians where AM and MM predominate. Age and stage remain
      the most critical prognostic factors across all subtypes.

PMID- 29052961
TI  - Amphiphilic small peptides for delivery of plasmid DNAs and siRNAs.
AB  - Although various delivery systems for nucleic acids have been reported,
      development of an efficient and non-toxic delivery carrier is still a key subject
      for gene therapy. To find new efficient delivery carriers for nucleic acids, we
      synthesized amphiphilic peptides composed of a guanidino group, an oleyl group,
      and a cysteine. We prepared both linear and branched types of peptides and found
      that the linear peptides were superior to the branched peptides as nucleic acid
      carriers. Our study also suggested that the intermolecular cysteine disulfides
      might allow the linear peptides to form the optimal particle sizes with nucleic
      acids for cellular uptake. The incorporation of a benzoyl group to the linear
      peptide gave rise to smaller, less suitable particle size with plasmid DNA, which
      greatly reduced the efficiency of plasmid DNA delivery. On the other hand, the
      benzoyl modification maintained the optimal particle size with siRNA, and
      interestingly it significantly enhanced the siRNA delivery. The higher efficiency
      is because the hydrophobicity from the benzoyl group might assist in interacting
      with the hydrophobic cell membrane. This demonstrates that a small structural
      change can modulate the preference of the carriers. Our study may provide an
      insight designing efficient delivery carriers.

PMID- 29052962
TI  - Bacterial catabolism of lignin-derived aromatics: New findings in a recent
      decade: Update on bacterial lignin catabolism.
AB  - Lignin is the most abundant phenolic polymer; thus, its decomposition by
      microorganisms is fundamental to carbon cycling on earth. Lignin breakdown is
      initiated by depolymerization catalysed by extracellular oxidoreductases secreted
      by white-rot basidiomycetous fungi. On the other hand, bacteria play a
      predominant role in the mineralization of lignin-derived heterogeneous low
      molecular-weight aromatic compounds. The outline of bacterial catabolic pathways
      for lignin-derived bi- and monoaryls are typically composed of the following
      sequential steps: (i) funnelling of a wide variety of lignin-derived aromatics
      into vanillate and syringate, (ii) O demethylation of vanillate and syringate to
      form catecholic derivatives and (iii) aromatic ring-cleavage of the catecholic
      derivatives to produce tricarboxylic acid cycle intermediates. Knowledge
      regarding bacterial catabolic systems for lignin-derived aromatic compounds is
      not only important for understanding the terrestrial carbon cycle but also
      valuable for promoting the shift to a low-carbon economy via biological lignin
      valorisation. This review summarizes recent progress in bacterial catabolic
      systems for lignin-derived aromatic compounds, including newly identified
      catabolic pathways and genes for decomposition of lignin-derived biaryls,
      transcriptional regulation and substrate uptake systems. Recent omics approaches
      on catabolism of lignin-derived aromatic compounds are also described.

PMID- 29052963
TI  - Deficiency of p38alpha in macrophage ameliorates d-galactosamine/TNF-alpha
      induced acute liver injury in mice.
AB  - Growing evidence suggests that hepatic macrophages play an important role in
      tissue repair after liver injury by coordinating the induction and resolution of
      inflammation, removing apoptotic cells, and promoting hepatocyte proliferation.
      Understanding the role of macrophages in the pathogenesis of liver injury will
      help pave the way to future therapeutics. Here, we investigated whether
      macrophage p38alpha plays a regulatory role in the tissue repair following d
      galactosamine (GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced acute liver
      injury. We found that macrophage p38alpha-deficient mice displayed decreased
      mortality and relieved liver injury as evident from less apoptosis, accelerated
      regeneration, decreased granulocytes recruitment, monocytes infiltration, and
      cytokine production after GalN/TNF-alpha treatment. Mechanistically, we found
      that p38 signaling was activated by lipopolysaccharide/interferon-gamma treatment
      but not by inteleukin-4 stimulation, while pharmaceutical inhibition of p38alpha
      induced a shift in polarization from M1 macrophages to M2 macrophages. Together,
      our results indicated that macrophage p38alpha signaling is involved in the
      pathogenesis of liver injury induced by GalN/TNF-alpha, and inhibition of
      p38alpha signaling in macrophage could ameliorate liver injury and accelerate
      regeneration, probably by promoting the polarization of macrophages from the M1
      phenotype to the M2 phenotype.

PMID- 29052964
TI  - Brief interactive psychoeducation for caregivers of patients with early phase
      psychosis in Yogyakarta, Indonesia.
AB  - AIM: Brief psychoeducation for families of psychotic patients has been shown to
      significantly increase family members' knowledge of the disorder. This increase
      is associated with reductions in relapse and rehospitalization. The aim of this
      study was to assess the effectiveness of brief psychoeducation about
      schizophrenia to caregivers of patients in early phases of psychotic disorders in
      Yogyakarta, Indonesia. METHODS: This study was a prospective, randomized trial
      with 2 parallel groups. Subjects were patients in the early phase of psychotic
      disorders and their respective caregivers. Inclusion criteria included a
      diagnosis of acute and transient psychotic disorders, schizophrenia,
      schizoaffective disorder or delusional disorder. Participants were randomly
      assigned to either control or intervention groups by means of paired simple
      randomization. A brief psychoeducation was conducted for both the patients and
      caregivers. The interventions were conducted in 4 interactive sessions, once per
      week. Effectiveness was measured using standardized instruments before the
      intervention, and at 1 and 6 months post-intervention. Assessment instruments
      included the Knowledge of Psychosis (KOP), the Compliance and Relapse Assessment,
      the Brief Psychiatric Rating Scale and the Positive and Negative Symptoms of
      Schizophrenia scale. RESULTS: Interventions improved KOP scores significantly in
      the intervention group. The intervention group had increased regularity of follow
      up with health providers and improved compliance. No statistically significant
      difference in relapses/rehospitalization was observed. CONCLUSIONS: This study
      demonstrated that brief psychoeducation with caregivers of patients with early
      phase psychosis was feasible in our setting, significantly improved caregivers'
      knowledge, and resulted in improved regularity of contact with health providers
      and compliance with pharmacotherapy.

PMID- 29052965
TI  - From vineyard to winery: a source map of microbial diversity driving wine
      fermentation.
AB  - Humans have been making wine for thousands of years and microorganisms play an
      integral part in this process as they not only drive fermentation, but also
      significantly influence the flavour, aroma and quality of finished wines. Since
      fruits are ephemeral, they cannot comprise a permanent microbial habitat; thus,
      an age-old unanswered question concerns the origin of fruit and ferment
      associated microbes. Here we use next-generation sequencing approaches to examine
      and quantify the roles of native forest, vineyard soil, bark and fruit habitats
      as sources of fungal diversity in ferments. We show that microbial communities in
      harvested juice and ferments vary significantly across regions, and that while
      vineyard fungi account for ~40% of the source of this diversity, uncultivated
      ecosystems outside of vineyards also prove a significant source. We also show
      that while communities in harvested juice resemble those found on grapes, these
      increasingly resemble fungi present on vine bark as the ferment proceeds.

PMID- 29052966
TI  - Targeting of C-type lectin-like receptor 2 or P2Y12 for the prevention of
      platelet activation by immunotherapeutic CpG oligodeoxynucleotides: reply.

PMID- 29052967
TI  - The island cotton NBS-LRR gene GbaNA1 confers resistance to the non-race 1
      Verticillium dahliae isolate Vd991.
AB  - Wilt caused by Verticillium dahliae significantly reduces cotton yields, as host
      resistance in commercially cultivated Gossypium species is lacking. Understanding
      the molecular basis of disease resistance in non-commercial Gossypium species
      could galvanize the development of Verticillium wilt resistance in cultivated
      species. Nucleotide-binding site leucine-rich repeat (NBS-LRR) proteins play a
      central role in plant defence against pathogens. In this study, we focused on the
      relationship between a locus enriched with eight NBS-LRR genes and Verticillium
      wilt resistance in G. barbadense. Independent virus-induced gene silencing of
      each of the eight NBS-LRR genes in G. barbadense cultivar Hai 7124 revealed that
      silencing of GbaNA1 alone compromised the resistance of G. barbadense to V.
      dahliae isolate Vd991. In cultivar Hai 7124, GbaNA1 could be induced by V.
      dahliae isolate Vd991 and by ethylene, jasmonic acid and salicylic acid. Nuclear
      protein localization of GbaNA1 was demonstrated by transient expression.
      Sequencing of the GbaNA1 orthologue in nine G. hirsutum accessions revealed that
      all carried a non-functional allele, caused by a premature peptide truncation. In
      addition, all 10 G. barbadense and nine G. hirsutum accessions tested carried a
      full-length (~1140 amino acids) homologue of the V. dahliae race 1 resistance
      gene Gbve1, although some sequence polymorphisms were observed. Verticillium
      dahliae Vd991 is a non-race 1 isolate that lacks the Ave1 gene. Thus, the
      resistance imparted by GbaNA1 appears to be mediated by a mechanism distinct from
      recognition of the fungal effector Ave1.

PMID- 29052968
TI  - Nonsteroidal estrogen receptor isoform-selective biphenyls.
AB  - Estrogen receptor (ER) has been a therapeutic target to treat ER-positive breast
      cancer, most notably by agents known as selective estrogen receptor modulators
      (SERMs). However, resistance and severe adverse effects of known drugs gave
      impetus to the search for newer agents with better therapeutic profile. ERalpha
      and ERbeta are two isoforms sharing 56% identity and having different
      physiological functions and expressions in various tissues. Only two residues
      differ in the active sites of the two isoforms motivating us to design isoform
      selective ligands. Guided by computational docking and molecular dynamics
      simulations, we have designed, synthesized, and tested, substituted biphenyl-2,6
      diethanones and their derivatives as potential agents targeting ERalpha. Four of
      the molecules synthesized exhibited preferential cytotoxicity in ERalpha+ cell
      line (MCF-7) compared to ERbeta+ cell line (MDA-MB-231). Molecular dynamics (MD)
      in combination with molecular mechanics-generalized Born surface area (MM-GBSA)
      methods could account for binding selectivity. Further cotreatment and E-screen
      studies with known ER ligands-estradiol (E2 ) and tamoxifen (Tam)-indicated
      isoform-selective anti-estrogenicity in ERalpha+ cell line which might be ER
      mediated. ERalpha siRNA silencing experiments further confirmed the ER selective
      nature of ligands.

PMID- 29052969
TI  - Long-distance ABA transport can mediate distal tissue responses by affecting
      local ABA concentrations.
AB  - Environmental stresses that perturb plant water relations influence abscisic acid
      (ABA) concentrations, but it is unclear whether long-distance ABA transport
      contributes to changes in local ABA levels. To determine the physiological
      relevance of ABA transport, we made reciprocal- and self-grafts of ABA-deficient
      flacca mutant and wild-type (WT) tomato plants, in which low phosphorus (P)
      conditions decreased ABA concentrations while salinity increased ABA
      concentrations. Whereas foliar ABA concentrations in the WT scions were rootstock
      independent under conditions, salinity resulted in long-distance transport of
      ABA: flacca scions had approximately twice as much ABA when grafted on WT
      rootstocks compared to flacca rootstocks. Root ABA concentrations were scion
      dependent: both WT and flacca rootstocks had less ABA with the flacca mutant
      scion than with the WT scion under conditions. In WT scions, whereas rootstock
      genotype had limited effects on stomatal conductance under conditions, a flacca
      rootstock decreased leaf area of stressed plants, presumably due to attenuated
      root-to-shoot ABA transport. In flacca scions, a WT rootstock decreased stomatal
      conductance but increased leaf area of stressed plants, likely due to enhanced
      root-to-shoot ABA transport. Thus, long-distance ABA transport can affect
      responses in distal tissues by changing local ABA concentrations.

PMID- 29052971
TI  - European Association for the Study of Diabetes 2017.
AB  - Ann M. Carracher, Payal H. Marathe, and Kelly L. Close are of Close Concerns
      (http://www.closeconcerns.com), a healthcare information company focused
      exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a
      periodical that brings together news and insights in these areas. Each month, the
      Journal of Diabetes includes this News feature, in which Carracher, Marathe, and
      Close review the latest developments relevant to researchers and clinicians.

PMID- 29052972
TI  - Impaired intestinal barrier function and relapsing digestive disease: Lessons
      from a porcine model of early life stress.
AB  - Within this issue of Neurogastroenterology and Motility, an article by Pohl et al
      highlights new insights from a powerful porcine model of the link between early
      life adversity and relapsing functional gastrointestinal disorders. Early weaning
      stress closely mimics the early life psychosocial stressors that have been linked
      to adult onset gastrointestinal dysfunction. This early weaning model provides
      reproducible and highly translatable outcomes in young stress-challenged pigs.
      Due to the convincingly comparable neurological and gastroenterological anatomy
      and physiology between pigs and human beings, gastrointestinal stress and injury
      studies utilizing swine models will provide invaluable insights to improve our
      understanding and treatment of gastrointestinal disease in human beings. Future
      studies to examine mechanisms underlying this link between early life adversity
      and functional gastrointestinal disorders will explore the roles of gender and
      hypomaturity in gastrointestinal responses to stress.

PMID- 29052973
TI  - Bimetallic Ru-Co Clusters Derived from a Confined Alloying Process within Zeolite
      Imidazolate Frameworks for Efficient NH3 Decomposition and Synthesis.
AB  - Herein, a series of carbocatalysts containing Ru-based clusters have been
      prepared by the assistance of zeolite-imidazolate frameworks (ZIFs). The
      introduction of Ru is based on the adsorption of well-defined Ru3(CO)12 within
      the cavity of ZIFs following decomposition at 900  degrees C. Moreover, without
      breaking the skeleton and porosity of ZIFs, the as-generated Ru species would
      bond with the Co nodes in situ to form bimetallic Ru-Co clusters if the Co
      bearing metal-organic frameworks were utilized as the host. Within the confined
      space of ZIFs, the assembly of Ru and Co could be rationally designed, and their
      structures could be sophisticatedly controlled at the atomic scale. Among these
      Ru-based compositions, the Ru-Co clusters@N-C exhibited remarkable catalytic
      activity for the NH3 decomposition to H2 and NH3 synthesis versus Ru-Co NPs@N-C,
      Ru clusters@N-C, and Ru NPs@N-C. This study may open up a new routine to
      synthesize metallic clusters or other subnano structures by the confinement of
      ZIFs.

PMID- 29052974
TI  - Functionalized Nickel Oxide Hole Contact Layers: Work Function versus
      Conductivity.
AB  - Nickel oxide (NiO) is a widely used material for efficient hole extraction in
      optoelectronic devices. However, its surface characteristics strongly depend on
      the processing history and exposure to adsorbates. To achieve controllability of
      the electronic and chemical properties of solution-processed nickel oxide (sNiO),
      we functionalize its surface with a self-assembled monolayer (SAM) of 4
      cyanophenylphosphonic acid. A detailed analysis of infrared and photoelectron
      spectroscopy shows the chemisorption of the molecules with a nominal layer
      thickness of around one monolayer and gives an insight into the chemical
      composition of the SAM. Density functional theory calculations reveal the
      possible binding configurations. By the application of the SAM, we increase the
      sNiO work function by up to 0.8 eV. When incorporated in organic solar cells, the
      increase in work function and improved energy level alignment to the donor does
      not lead to a higher fill factor of these cells. Instead, we observe the
      formation of a transport barrier, which can be reduced by increasing the
      conductivity of the sNiO through doping with copper oxide. We conclude that the
      widespread assumption of maximizing the fill factor by only matching the work
      function of the oxide charge extraction layer with the energy levels in the
      active material is a too narrow approach. Successful implementation of interface
      modifiers is only possible with a sufficiently high charge carrier concentration
      in the oxide interlayer to support efficient charge transfer across the
      interface.

PMID- 29052975
TI  - Trends in Drinking Water Nitrate Violations Across the United States.
AB  - Drinking water maximum contaminant levels (MCL) are established by the U.S. EPA
      to protect human health. Since 1975, U.S. public water suppliers have reported
      MCL violations to the national Safe Drinking Water Information System (SDWIS).
      This study assessed temporal and geographic trends for violations of the 10 mg
      nitrate-N L-1 MCL in the conterminous U.S. We found that the proportion of
      systems in violation for nitrate significantly increased from 0.28% to 0.42% of
      all systems between 1994 and 2009 and then decreased to 0.32% by 2016. The number
      of people served by systems in violation decreased from 1.5 million in 1997 to
      200 000 in 2014. Periodic spikes in people served were often driven by just one
      large system in violation. On average, Nebraska and Delaware had the greatest
      proportion of systems in violation (2.7% and 2.4%, respectively), while Ohio and
      California had the greatest average annual number of people served by systems in
      violation (278 374 and 139 149 people, respectively). Even though surface water
      systems that serve more people have been improving over time, groundwater systems
      in violation and average duration of violations are increasing, indicating
      persistent nitrate problems in drinking water.

PMID- 29052976
TI  - Engineering Enhanced Pore Sizes Using FhuA Delta1-160 from E. coli Outer Membrane
      as Template.
AB  - Biological membranes are the perfect example of a molecular filter using membrane
      channels to control the permeability of small water-soluble molecules. To allow
      filtering of larger hydrophilic molecules we started from the known mutant
      channel FhuA Delta1-160 in which the cork domain closing the channel had been
      removed. Here we further expand the pore diameter by copying the amino acid
      sequence of two beta-strands in a stepwise manner increasing the total number of
      beta-strands from 22 to 34. The pore size of the respective expanded channel
      protein was characterized by single-channel conductance. Insertion of additional
      beta-strands increased the pore conductance but also induced more ion current
      flickering on the millisecond scale. Further, polymer exclusion measurements were
      performed by analyzing single-channel conductance in the presence of differently
      sized polyethylene glycol of known polymer random coil radii. The conclusion from
      channel conductance of small channel penetrating polymers versus larger excluded
      ones suggested an increase in pore radii from 1.6 nm for FhuA Delta1-160 up to a
      maximum of about 2.7 nm for +8 beta insertion. Integration of more beta-strand
      caused instability of the channel and exclusion of smaller sized polymer. FhuA
      Delta1-160 + 10 beta and FhuA Delta1-160 + 12 beta effective radius decreased to
      1.4 and 1.3 nm, respectively, showing the limitations of this approach.

PMID- 29052977
TI  - Cross-Regulation of Iron and Glucose Metabolism in Response to Infection.

PMID- 29052978
TI  - Natural Biowaste-Cocoon-Derived Granular Activated Carbon-Coated ZnO Nanorods: A
      Simple Route To Synthesizing a Core-Shell Structure and Its Highly Enhanced UV
      and Hydrogen Sensing Properties.
AB  - Granular activated carbon (GAC) materials were prepared via simple gas activation
      of silkworm cocoons and were coated on ZnO nanorods (ZNRs) by the facile
      hydrothermal method. The present combination of GAC and ZNRs shows a core-shell
      structure (where the GAC is coated on the surface of ZNRs) and is exposed by
      systematic material analysis. The as-prepared samples were then fabricated as
      dual-functional sensors and, most fascinatingly, the as-fabricated core-shell
      structure exhibits better UV and H2 sensing properties than those of as
      fabricated ZNRs and GAC. Thus, the present core-shell structure-based H2 sensor
      exhibits fast responses of 11% (10 ppm) and 23.2% (200 ppm) with ultrafast
      response and recovery. However, the UV sensor offers an ultrahigh
      photoresponsivity of 57.9 A W-1, which is superior to that of as-grown ZNRs (0.6
      A W-1). Besides this, switching photoresponse of GAC/ZNR core-shell structures
      exhibits a higher switching ratio (between dark and photocurrent) of 1585, with
      ultrafast response and recovery, than that of as-grown ZNRs (40). Because of the
      fast adsorption ability of GAC, it was observed that the finest distribution of
      GAC on ZNRs results in rapid electron transportation between the conduction bands
      of GAC and ZNRs while sensing H2 and UV. Furthermore, the present core-shell
      structure-based UV and H2 sensors also well-retained excellent sensitivity,
      repeatability, and long-term stability. Thus, the salient feature of this
      combination is that it provides a dual-functional sensor with biowaste cocoon and
      ZnO, which is ecological and inexpensive.

PMID- 29052979
TI  - Tetranuclear Fe Clusters with a Varied Interstitial Ligand: Effects on the
      Structure, Redox Properties, and Nitric Oxide Activation.
AB  - A new series of tetranuclear Fe clusters displaying an interstitial MU4-F ligand
      was prepared for a comparison to previously reported MU4-O analogues. With a
      single nitric oxide (NO) coordinated as a reporter of small-molecule activation,
      the MU4-F clusters were characterized in five redox states, from FeII3{FeNO}8 to
      FeIII3{FeNO}7, with NO stretching frequencies ranging from 1680 to 1855 cm-1,
      respectively. Despite accessing more reduced states with an F- bridge, a two
      electron reduction of the distal Fe centers is necessary for the MU4-F clusters
      to activate NO to the same degree as the MU4-O system; consequently, NO
      reactivity is observed at more positive potentials with MU4-O than MU4-F.
      Moreover, the MU4-O ligand better translates redox changes of remote metal
      centers to diatomic ligand activation. The implication for biological active
      sites is that the higher-charge bridging ligand is more effective in tuning
      cluster properties, including the involvement of remote metal centers, for small
      molecule activation.

PMID- 29052980
TI  - Decabromodiphenyl Ether (DecaBDE) in Electrical and Electronic Equipment in
      Japan: Stock, Emission, and Substitution Evaluation.
AB  - DecaBDE has been widely used as flame retardant in electrical and electronic
      equipment (EEE). It has recently been listed in Annex A of the Stockholm
      Convention. The time series flow, stock, and emission of DecaBDE in EEE in Japan
      were quantified. On this basis, a risk/risk trade-off analysis of substituting
      DecaBDE with triphenyl phosphate (TPhP) that is one possible phosphorus-based
      alternative was conducted. The stock of DecaBDE reached a maximum of ~42 000 t in
      1995. Even though the demand flow was negligible in 2030, the stock was modeled
      to be still ~470 t. The outflow of DecaBDE, from the use phase to the disposal
      phase, peaked at ~4500 t/yr. in 2001. The DecaBDE emission to atmosphere was
      mainly derived from the production phase before 1990. The use phase became the
      largest contributor to the total emission from 1995 to 2000. Whereas the disposal
      phase dominated the total emission from 2000 onward. In the substitution
      analysis, a trade-off between human and ecological health effect was revealed in
      case of replacing DecaBDE with TPhP. This study attempted to give an overall
      picture of DecaBDE application at national level providing insights into relevant
      environmental policy making.

PMID- 29052981
TI  - Cation-Induced Dimerization of Crown-Substituted Phthalocyanines by Complexation
      with Rubidium Nicotinate As Revealed by X-ray Structural Data.
AB  - The supramolecular dimeric complex [(MU-oxo)bis(tetra-15-crown-5
      phthalocyaninato)(nicotinato)aluminum(III)]tetra(rubidium) bis(nicotinate) was
      prepared by addition of an excess of a methanol solution of rubidium nicotinate
      to a chloroform solution of the aluminum crown-phthalocyaninate,
      [(HO)Al(15C5)4Pc]. A single-crystal X-ray diffraction study of
      {[Rb4(NicAl(15C5)4Pc)2(MU-O)]2+(Nic-)2}.2.36HNic.11H2O demonstrated that two
      molecules of the aluminum crown-phthalocyaninate nicotinate are connected through
      an Al-O-Al bridge supported by sandwiching of crown ether moieties by Rb+
      cations.

PMID- 29052982
TI  - Designing a Thermoelectric Copper-Rich Sulfide from a Natural Mineral: Synthetic
      Germanite Cu22Fe8Ge4S32.
AB  - This study shows that the design of copper-rich sulfides by mimicking natural
      minerals allows a new germanite-type sulfide Cu22Fe8Ge4S32 with promising
      thermoelectric properties to be synthesized. The Mossbauer spectroscopy and X-ray
      diffraction analyses provide evidence that the structure of our synthetic
      compound differs from that of the natural germanite mineral Cu26Fe4Ge4S32 by its
      much higher Cu+/Cu2+ ratio and different cationic occupancies. The coupled
      substitution Cu/Fe in the Cu26-xFe4+xGe4S32 series also appears as a promising
      approach to optimize the thermoelectric properties. The electrical resistivity,
      which decreases slightly as the temperature increases, shows that these materials
      exhibit a semiconducting behavior, but are at the border of a metallic state. The
      magnitudes of the electrical resistivity and Seebeck coefficient increase with x,
      which suggests that Fe for Cu substitution decreases the hole concentration. The
      thermal conductivity decreases as the temperature increases leading to a
      moderately low value of 1.2 W m-1 K-1 and a maximum ZT value of 0.17 at 575 K.

PMID- 29052983
TI  - In Vivo Biochemistry: Single-Cell Dynamics of Cyclic Di-GMP in Escherichia coli
      in Response to Zinc Overload.
AB  - Intracellular signaling enzymes drive critical changes in cellular physiology and
      gene expression, but their endogenous activities in vivo remain highly
      challenging to study in real time and for individual cells. Here we show that
      flow cytometry can be performed in complex media to monitor single-cell
      population distributions and dynamics of cyclic di-GMP signaling, which controls
      the bacterial colonization program. These in vivo biochemistry experiments are
      enabled by our second-generation RNA-based fluorescent (RBF) biosensors, which
      exhibit high fluorescence turn-on in response to cyclic di-GMP. Specifically, we
      demonstrate that intracellular levels of cyclic di-GMP in Escherichia coli are
      repressed with excess zinc, but not with other divalent metals. Furthermore, in
      both flow cytometry and fluorescence microscopy setups, we monitor the dynamic
      increase in cellular cyclic di-GMP levels upon zinc depletion and show that this
      response is due to de-repression of the endogenous diguanylate cyclase DgcZ. In
      the presence of zinc, cells exhibit enhanced cell motility and increased
      sensitivity to antibiotics due to inhibited biofilm formation. Taken together,
      these results showcase the application of RBF biosensors in visualizing single
      cell dynamic changes in cyclic di-GMP signaling in direct response to
      environmental cues such as zinc and highlight our ability to assess whether
      observed phenotypes are related to specific signaling enzymes and pathways.

PMID- 29052984
TI  - Complex Structural Landscape of Titanium Organophosphonates: Isolation of
      Structurally Related Ti4, Ti5, and Ti6 Species and Mechanistic Insights.
AB  - [Ti(acac)2(OiPr)2] reacts with tert-butylphosphonic acid to yield a series of
      titanium organophosphonates such as tetranuclear [Ti4(acac)4(MU-O)2(MU
      tBuPO3)2(MU-tBuPO3H)4].2CH3CN (1), pentanuclear [Ti5(acac)5(MU-O)2(OiPr)(MU
      tBuPO3)4(MU-tBuPO3H)2] (2), hexanuclear [Ti6(acac)6(MU-O)2(OiPr)2(MU-tBuPO3)6]
      (3), or [Ti6(acac)6(MU-O)3(OiPr)(MU-tBuPO3)5(MU-tBuPO3H)].2CH3CN (4). The
      isolation of each of these products in pure form depends on the molar ratio of
      the reactants or the solvent medium. Among these, 3 is obtained as the only
      product when the reaction is conducted in CH2Cl2. The structural analysis reveals
      that a simple cluster growth route relates the clusters 1-4 to each other and
      that a reactive cyclic single-4-ring titanophosphonate
      [Ti(acac)(OiPr)2(tBuPO3H)]2 is the fundamental building block. While the
      tetranuclear 1 has structural resemblance to the D4R building block of zeolites,
      the hexanuclear clusters 3 and 4 have the shape of zeolitic D6R building blocks.
      The presence of adventitious water in the phosphonic acid (arising from small
      quantities of hydrogen-bonded water) results in the formation of MU-O2- bridges
      across an adjacent pair of titanium centers in clusters 1-4. To further verify
      the stability of the hexanuclear cluster over other structural forms, the
      reaction of tBuPO3H2 was performed with [Ti(acac)2(O)], instead of
      Ti(acac)2(OiPr)2, in CH3CN to yield [Ti6(acac)6(MU-O)4(MU-tBuPO3)4(MU
      tBuPO3H)2].2CH3CN (5). Compound 5 exhibits a core structure similar to those of 3
      and 4 with small variations in the intracluster Ti-O-Ti linkage. Compound 3 is an
      efficient and selective catalyst for olefin epoxidation under both homogeneous
      and heterogeneous conditions.

PMID- 29052985
TI  - Occurrence, Loading, and Exposure of Atmospheric Particle-Bound POPs at the
      African and European Edges of the Western Mediterranean Sea.
AB  - A comparative study for 62 toxic chemicals based on the simultaneous monthly
      collection of aerosol samples during 2015-2016 in two coastal cities at both the
      African (Bizerte, Tunisia) and European (Marseille, France) edges of the Western
      Mediterranean basin is presented. Legacy polychlorinated biphenyls (?18PCBs) and
      polychlorinated dibenzo-p-dioxins and dibenzofurans (?17PCDD/Fs) show generally
      higher median levels at the African edge (2.1 and 0.2 pg m-3, respectively)
      compared to the European coastal site (1.0 and 0.08 pg m-3, respectively).
      Contrarily, the "emerging" polybrominated diphenyl ethers' (?27PBDEs) median
      concentrations were higher in Marseille (~9.0 pg m-3) compared to Bizerte (~6.0
      pg m-3). Different past usages and current emission patterns were found at both
      edges of the Western Mediterranean, most probably linked to the respective
      different regulatory frameworks for toxic chemicals. Our results indicate that
      the total organic carbon (TOC) and/or the elemental carbon (EC) contents in the
      atmospheric aerosol may have a stronger effect than the total suspended particle
      (TSP) content as a whole on the spatial-temporal variability and the long-range
      atmospheric transport potential of the studied POPs. A "jumping" of the PBDE
      local atmospheric stocks from the Northwestern European Mediterranean edge to the
      Northwestern African coast seems to be possible under favorable conditions at
      present. While a higher PBDE median loading is estimated for the Marseille area
      (~550 ng m-2 y-1) compared to Bizerte (~400 ng m-2 y-1), the median PCB and
      PCDD/F dry deposition fluxes were higher at the African site, resulting in a 3
      fold higher toxic equivalent (TEQ) loading of dioxin-like pollutants (400 pg TEQ
      m-2 y-1) compared to Marseille (~140 pg TEQ m-2 y-1), with potential implications
      for aquatic organisms. However, the inhalation exposure assessment points to a
      minimum risk for human health at both sites.

PMID- 29052986
TI  - Zinc Tin Chalcogenide Complexes and Their Evaluation as Molecular Precursors for
      Cu2ZnSnS4 (CZTS) and Cu2ZnSnSe4 (CZTSe).
AB  - A series of five heteronuclear zinc tin chalcogenide complexes with the general
      formula [(tmeda)Zn(SnR2)2E3] (1-R, E = S; R = Me, Ph, tBu; 2-R, E = Se; R = Ph,
      tBu) have been synthesized and characterized by X-ray crystal structure analysis.
      In all cases, the six-membered ZnSn2E3 rings exhibit twist boat conformation. The
      presence of the molecular structures in solution is confirmed by 119Sn and 77Se
      NMR spectroscopy. Cothermolysis experiments using a mixture of complexes 1-R or 2
      R and [(iPr3PCu)2(EC2H4E)]2 as a copper source were monitored by thermogravimetry
      and temperature dependent X-ray powder diffraction to examine the thermolysis
      reaction. According to Rietveld refinement, the solid residue consists of
      Cu2ZnSnS4 (up to 78 wt %) or Cu2ZnSnSe4 (up to 43 wt %) as the main product,
      respectively.

PMID- 29052987
TI  - Triplet Sensitized Photodenitrogenation of Delta2-1,2,3-Triazolines To Form
      Aziridines in Solution and in the Crystalline State: Observation of the Triplet
      1,3-Alkyl-aminyl Biradical.
AB  - Taking advantage of an operationally simple technique to perform transmission
      pump-probe spectroscopy in crystalline solids, based on the use nanocrystalline
      suspensions in water, we analyzed the intermediates in the photodenitrogenation
      of a Delta2-1,2,3-triazoline bearing a benzophenone group that served as an
      internal triplet sensitizer. Measurements carried out in acetonitrile solution
      revealed the formation of a transient with a lambdamax= 570 nm with a lifetime of
      70 ns. Measurements in the solid state displayed an analogous blue-shifted
      transient with a lambdamax= 510 nm that first grows and then decays with time
      constants of 63 and 270 ns, respectively. Based on the comparison of the observed
      transient spectra with the one obtained from an independently generated aminyl
      radical, we assign it to the corresponding 1,3,-alkyl-aminyl biradical. We
      conclude that triplet state denitrogenation and the subsequent intersystem
      crossing-limited product formation are slower in the solid state than in
      solution.

PMID- 29052988
TI  - Ionic Strength-Mediated Phase Transitions of Surface-Adsorbed DNA on Single
      Walled Carbon Nanotubes.
AB  - Single-stranded DNA oligonucleotides have unique, and in some cases sequence
      specific molecular interactions with the surface of carbon nanotubes that remain
      the subject of fundamental study. In this work, we observe and analyze a generic,
      ionic strength-mediated phase transition exhibited by over 25 distinct
      oligonucleotides adsorbed to single-walled carbon nanotubes (SWCNTs) in colloidal
      suspension. The phase transition occurs as monovalent salts are used to modify
      the ionic strength from 500 mM to 1 mM, causing a reversible reduction in the
      fluorescence quantum yield by as much as 90%. The phase transition is only
      observable by fluorescence quenching within a window of pH and in the presence of
      dissolved O2, but occurs independently of this optical quenching. The negatively
      charged phosphate backbone increases (decreases) the DNA surface coverage on an
      areal basis at high (low) ionic strength, and is well described by a two-state
      equilibrium model. The resulting quantitative model is able to describe and link,
      for the first time, the observed changes in optical properties of DNA-wrapped
      SWCNTs with ionic strength, pH, adsorbed O2, and ascorbic acid. Cytosine
      nucleobases are shown to alter the adhesion of the DNA to SWCNTs through direct
      protonation from solution, decreasing the driving force for this phase
      transition. We show that the phase transition also changes the observed SWCNT
      corona phase, modulating the recognition of riboflavin. These results provide
      insight into the unique molecular interactions between DNA and the SWCNT surface,
      and have implications for molecular sensing, assembly, and nanoparticle
      separations.

PMID- 29052989
TI  - CO2 Complexes with Five-Membered Heterocycles: Structure, Topology, and
      Spectroscopic Characterization.
AB  - In a first step toward the rational design of macrocyclic structures optimized
      for CO2 capture, we systematically explored the potential of 30 five-membered
      aromatic heterocycles to establish coordinating complexes with this pollutant.
      The interactions between the two moieties were studied in several orientations,
      and the obtained complexes were analyzed in terms of electron density and
      vibrational fingerprint. The former is an aid to provide an in-depth knowledge of
      the interaction, whereas the latter should help to select structural motifs that
      have not only good complexation properties but also diagnostic spectroscopic
      signals.

PMID- 29052990
TI  - Spatial Screening of Hemagglutinin on Influenza A Virus Particles: Sialyl-LacNAc
      Displays on DNA and PEG Scaffolds Reveal the Requirements for Bivalency Enhanced
      Interactions with Weak Monovalent Binders.
AB  - Attachment of the Influenza A virus onto host cells involves multivalent
      interactions between virus surface hemagglutinin (HA) and sialoside-containing
      glyco ligands. Despite the development of extremely powerful multivalent binders
      of the Influenza virus and other viruses, comparably little is known about the
      optimal spacing of HA ligands, which ought to bridge binding sites within or
      across the trimeric HA molecules. To explore the criteria for ligand economical
      high affinity binding, we systematically probed distance-affinity relationships
      by means of two differently behaving scaffold types based on (i) flexible
      polyethylene glycol (PEG) conjugates and (ii) rigid self-assembled DNA.PNA
      complexes. The bivalent scaffolds presented two sialyl-LacNAc ligands in 23-101 A
      distance. A combined analysis of binding by means of microscale thermophoresis
      measurements and statistical mechanics models exposed the inherent limitations of
      PEG-based spacers. Given the distance requirements of HA, the flexibility of PEG
      scaffolds is too high to raise the effective concentration of glyco ligands above
      a value that allows interactions with the low affinity binding site. By contrast,
      spatial screening with less flexible, self-assembled peptide nucleic acid
      (PNA).DNA complexes uncovered a well-defined and, surprisingly, bimodal distance
      affinity relationship for interactions of the Influenza A virus HA with bivalent
      displays of the natural sialyl-LacNAc ligand. Optimal constructs conferred 103
      fold binding enhancements with only two ligands. We discuss the existence of
      secondary binding sites and shine light on the preference for intramolecular
      rather than intermolecular recognition of HA trimers on the virus surface.

PMID- 29052991
TI  - Transition Metal Single-Molecule Magnets: A {Mn31} Nanosized Cluster with a Large
      Energy Barrier of ~60 K and Magnetic Hysteresis at ~5 K.
AB  - The first {Mn31} cluster (1) has been prepared from carboxylate ions and the
      chelating/bridging ligand alpha-methyl-2-pyridine-methanol. Compound 1 possesses
      a unique nanosized structural topology with one of the largest energy barriers
      reported to-date for high-nuclearity 3d-metal clusters. Single-crystal magnetic
      hysteresis studies reveal the presence of hysteresis loops below 5 K, one of the
      highest temperatures below which molecular hysteresis has been observed for 3d
      based SMMs.

PMID- 29052992
TI  - Camphorsulfonic Acid Catalyzed One-Pot Three-Component Reaction for the Synthesis
      of Fused Quinoline and Benzoquinoline Derivatives.
AB  - A simple and an efficient one-pot three-component reaction of arylamines,
      aromatic aldehydes, and cyclic ketones was described for the synthesis of various
      fused quinoline, benzoquinoline, and naphthoquinoline derivatives by using
      camphorsulfonic acid as a catalyst. The exploitation of pregnenolone steroid for
      benzoquinolines and terephthalaldehyde for bis-benzoquinolines synthesis was
      achieved with 68-75% yields. The reactivity of arylamines and the mechanistic
      study for the formation of benzoquinoline was described precisely. The present
      protocol offers a great potential for atom-economy under mild conditions.

PMID- 29052993
TI  - Catalytic Asymmetric Roskamp Reaction of Silyl Diazoalkane: Synthesis of
      Enantioenriched alpha-Silyl Ketone.
AB  - A catalytic enantioselective Roskamp reaction of silyl diazoalkane to synthesize
      a highly optically active alpha-silyl ketone from aldehydes is described. In the
      presence of a chiral oxazaborolidinium ion catalyst, the reaction provides alpha
      chiral silyl ketones with good yields (up to 97%) and high enantioselectivities
      (up to >99% ee). In addition, a one-pot procedure using an asymmetric
      Roskamp/reduction strategy gives highly optically active syn-beta-hydroxysilane
      in good yields (up to 94%) with high enantioselectivities (up to 99% ee) and syn
      stereoselectivities (>20:1).

PMID- 29052994
TI  - Force-Induced Calpain Cleavage of Talin Is Critical for Growth, Adhesion
      Development, and Rigidity Sensing.
AB  - Cell growth depends upon formation of cell-matrix adhesions, but mechanisms
      detailing the transmission of signals from adhesions to control proliferation are
      still lacking. Here, we find that the scaffold protein talin undergoes force
      induced cleavage in early adhesions to produce the talin rod fragment that is
      needed for cell cycle progression. Expression of noncleavable talin blocks cell
      growth, adhesion maturation, proper mechanosensing, and the related property of
      EGF activation of motility. Further, the expression of talin rod in the presence
      of noncleavable full-length talin rescues cell growth and other functions. The
      cleavage of talin is found in early adhesions where there is also rapid turnover
      of talin that depends upon calpain and TRPM4 activity as well as the generation
      of force on talin. Thus, we suggest that an important function of talin is its
      control over cell cycle progression through its cleavage in early adhesions.

PMID- 29052995
TI  - B(C6F5)3-Catalyzed Regioselective Deuteration of Electron-Rich Aromatic and
      Heteroaromatic Compounds.
AB  - Deuterium labeled compounds find widespread application in life science. Herein,
      the deuteration of electron-rich (hetero)aromatic compounds employing B(C6F5)3 as
      the catalyst and D2O as the deuterium source is reported. This protocol is highly
      efficient, simply manipulated, and successfully applied in the deuteration of 23
      substrates including natural neurotransmitter-like melatonin. It is assumed that
      the weakening of the O-D bond ultimately results in the formation of
      electrophilic D+.

PMID- 29052996
TI  - Spontaneous and Flow-Driven Interfacial Phase Change: Dynamics of Microemulsion
      Formation at the Pore Scale.
AB  - The dynamic behavior of microemulsion-forming water-oil-amphiphiles mixtures is
      investigated in a 2.5D micromodel. The equilibrium phase behavior of such
      mixtures is well-understood in terms of macroscopic phase transitions. However,
      what is less understood and where experimental data are lacking is the coupling
      between the phase change and the bulk flow. Herein, we study the flow of an
      aqueous surfactant solution-oil mixture in porous media and analyze the
      dependence of phase formation and spatial phase configurations on the bulk flow
      rate. We find that a microemulsion forms instantaneously as a boundary layer at
      the initial surface of contact between the surfactant solution and oil. The
      boundary layer is temporally continuous because of the imposed convection. In
      addition to the imposed flow, we observe spontaneous pulsed Marangoni flows that
      drag the microemulsion and surfactant solution into the oil stream, forming large
      (macro)emulsion droplets. The formation of the microemulsion phase at the
      interface distinguishes the situation from that of the more common Marangoni flow
      with only two phases present. Additionally, an emulsion forms via liquid-liquid
      nucleation or the Ouzo effect (i.e., spontaneous emulsification) at low flow
      rates and via mechanical mixing at high flow rates. With regard to multiphase
      flow, contrary to the common belief that the microemulsion is the wetting liquid,
      we observe that the minor oil phase wets the solid surface. We show that a
      layered flow pattern is formed because of the out-of-equilibrium phase behavior
      at high volumetric flow rates (order of 2 m/day) where advection is much faster
      than the diffusive interfacial mass transfer and transverse mixing, which promote
      equilibrium behavior. At lower flow rates (order of 30 cm/day), however, the
      dynamic and equilibrium phase behaviors are well-correlated. These results
      clearly show that the phase change influences the macroscale flow behavior.

PMID- 29052997
TI  - Hybrid Macrocycles of Subporphyrins and Triphyrins.
AB  - The dibenzofuran/dibenzothiophene-based nonaromatic hybrid macrocycles,
      exhibiting the features of both contracted macrocycles, subporphyrins and
      triphyrins, have been synthesized under simple reaction conditions using readily
      available precursors. The monoanionic new macrocyclic ligands with three donor
      atoms, such as two pyrrole nitrogens and one dibenzofuran oxygen or
      dibenzothiophene sulfur, readily form Re(I) complexes.

PMID- 29052998
TI  - 3D Imaging of a Dislocation Loop at the Onset of Plasticity in an Indented
      Nanocrystal.
AB  - Structural quality and stability of nanocrystals are fundamental problems that
      bear important consequences for the performances of small-scale devices. Indeed,
      at the nanoscale, their functional properties are largely influenced by elastic
      strain and depend critically on the presence of crystal defects. It is thus of
      prime importance to be able to monitor, by noninvasive means, the stability of
      the microstructure of nano-objects against external stimuli such as mechanical
      load. Here we demonstrate the potential of Bragg coherent diffraction imaging for
      such measurements, by imaging in 3D the evolution of the microstructure of a
      nanocrystal exposed to in situ mechanical loading. Not only could we observe the
      evolution of the internal strain field after successive loadings, but we also
      evidenced a transient microstructure hosting a stable dislocation loop. The
      latter is fully characterized from its characteristic displacement field. The
      mechanical behavior of this small crystal is clearly at odds with what happens in
      bulk materials where many dislocations interact. Moreover, this original in situ
      experiment opens interesting possibilities for the investigation of plastic
      deformation at the nanoscale.

PMID- 29053000
TI  - [Articles of the Hungarian Medical Journal from May, 2000].

PMID- 29052999
TI  - Impulsivity and compulsivity in Internet gaming disorder: A comparison with
      obsessive-compulsive disorder and alcohol use disorder.
AB  - Background and aims Internet gaming disorder (IGD) is characterized by a loss of
      control and a preoccupation with Internet games leading to repetitive behavior.
      We aimed to compare the baseline neuropsychological profiles in IGD, alcohol use
      disorder (AUD), and obsessive-compulsive disorder (OCD) in the spectrum of
      impulsivity and compulsivity. Methods A total of 225 subjects (IGD, N = 86; AUD,
      N = 39; OCD, N = 23; healthy controls, N = 77) were administered traditional
      neuropsychological tests including Korean version of the Stroop Color-Word test
      and computerized neuropsychological tests, including the stop signal test (SST)
      and the intra-extra dimensional set shift test (IED). Results Within the domain
      of impulsivity, the IGD and OCD groups made significantly more direction errors
      in SST (p = .003, p = .001) and showed significantly delayed reaction times in
      the color-word reading condition of the Stroop test (p = .049, p = .001). The OCD
      group showed the slowest reading time in the color-word condition among the four
      groups. Within the domain of compulsivity, IGD patients showed the worst
      performance in IED total trials measuring attentional set shifting ability among
      the groups. Conclusions Both the IGD and OCD groups shared impairment in
      inhibitory control functions as well as cognitive inflexibility. Neurocognitive
      dysfunction in IGD is linked to feature of impulsivity and compulsivity of
      behavioral addiction rather than impulse dyscontrol by itself.

PMID- 29053002
TI  - [Articles of the Hungarian Medical Journal from January, 2000].

PMID- 29053001
TI  - [Articles of the Hungarian Medical Journal from July, 2000].

PMID- 29053003
TI  - Detoxification of cancerogenic compounds by lactic acid bacteria strains.
AB  - Carcinogens in food are an important issue that threat people's health right now.
      Lactic acid bacteria (LAB) strains as well-known probiotics have shown numerous
      perspectives in being used as a good food additive to confront cancerogenic
      compounds in recent years. Some LAB strains can remove cancerogenic compounds
      from medium environment via direct physical binding and avoid re-pollution of
      poisonous secondary metabolites which are generated from degradation of
      cancerogenic compounds. This article presents a whole overview of the physical
      binding of LAB strains to such common cancerogenic compounds existed in food and
      feed environments as mycotoxins, polycyclic aromatic hydrocarbons (PAHs),
      heterocyclic amines (HAs) and pthalic acid esters (PAEs).In most cases, summaries
      of these published researches show that the binding of LAB strains to
      cancerogenic compounds is a physical process. Binding sites generally take place
      in cell wall, and peptidoglycan from LAB cells is the chief binding site. The
      adsorption of lactic acid bacteria to cancerogenic compounds is strain-specific.
      Specially, the strains from the two genera Lactobacillus and Bifidobacterium show
      a better potential in binding cancerogenic compounds. Moreover, we firstly used
      molecular dynamic computer model as a highly potential tool to simulate the
      binding behavior of peptidoglycan from Lactobacillus acidophilus to DBP, one of
      pthalic acid esters with genetic toxicity. It was seen that the theoretical data
      were quite consistent with the experimental results in terms of the ability of
      this bacterium to bind DBP. Also, the toxicity reduction of cancerogenic
      compounds by LAB strains could be achieved either in gastrointestinal model or
      animal tests and clinical researches as well. In conclusion, carefully selected
      LAB strains should be a good solution as one of safety strategies to reduce
      potential risk of cancerogenic compounds from food-based products.

PMID- 29053004
TI  - Effect of Inositol and its Derivatives on Diabetes: A Systematic Review.
AB  - A growing body of research has investigated the association between inositol and
      diabetes. The purpose of this review is to report through a systematic way the
      current scientific evidence relating potential benefits of inositol isomers on
      diabetes/gestational diabetes. The screening of the studies published last decade
      was performed in 4 databases (Pubmed-Web of Science-The Cochrane Library-Lilacs).
      Among the 1640 studies identified in the search, only 26 studies had sufficient
      data to be included in the systematic review. The available literature suggests
      that inositol seems to be provide improvements in fasting blood glucose and other
      biochemical results, which are among the most important parameters in diabetic
      individuals. Although there are some studies demonstrating that inositol may be
      effective in prevention and treatment of diabetes/ gestational diabetes,
      conduction of studies with larger sample and longer follow-up duration is
      required for it to be represented as an effective strategy in management of
      diabetes.

PMID- 29053006
TI  - [Articles of the Hungarian Medical Journal from December, 2000].

PMID- 29053005
TI  - Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain
      Quiescence and to Prevent Lung Injury.
AB  - RATIONALE: Potentially hazardous CpG-containing cell-free mitochondrial DNA (cf
      mtDNA) is routinely released into the circulation and is associated with
      morbidity and mortality in critically ill patients. How the body avoids
      inappropriate innate immune activation by cf-mtDNA remains unknown. Because red
      blood cells (RBCs) modulate innate immune responses by scavenging chemokines, we
      hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct
      scavenging of CpG-containing DNA. OBJECTIVES: To determine the mechanisms of CpG
      DNA binding to RBCs and the effects of RBC-mediated DNA scavenging on lung
      inflammation. METHODS: mtDNA on murine RBCs was measured under basal conditions
      and after systemic inflammation. mtDNA content on human RBCs from healthy control
      subjects and trauma patients was measured. Toll-like receptor 9 (TLR9) expression
      on RBCs and TLR9-dependent binding of CpG-DNA to RBCs were determined. A murine
      model of RBC transfusion after CpG-DNA-induced lung injury was used to
      investigate the role of RBC-mediated DNA scavenging in mitigating lung injury in
      vivo. MEASUREMENTS AND MAIN RESULTS: Under basal conditions, RBCs bind CpG-DNA.
      The plasma-to-RBC mtDNA ratio is low in naive mice and in healthy volunteers but
      increases after systemic inflammation, demonstrating that the majority of cf
      mtDNA is RBC-bound under homeostatic conditions and that the unbound fraction
      increases during inflammation. RBCs express TLR9 and bind CpG-DNA through TLR9.
      Loss of TLR9-dependent RBC-mediated CpG-DNA scavenging increased lung injury in
      vivo. CONCLUSIONS: RBCs homeostatically bind mtDNA, and RBC-mediated DNA
      scavenging is essential in mitigating lung injury after CpG-DNA. Our data suggest
      a role for RBCs in regulating lung inflammation during disease states where cf
      mtDNA is elevated, such as sepsis and trauma.

PMID- 29053007
TI  - [Articles of the Hungarian Medical Journal from March, 2000].

PMID- 29053008
TI  - [Articles of the Hungarian Medical Journal from November, 2000].

PMID- 29053010
TI  - [Articles of the Hungarian Medical Journal from September, 2000].

PMID- 29053009
TI  - Plasma Exosomes Disrupt the Blood-Brain Barrier in Children with Obstructive
      Sleep Apnea and Neurocognitive Deficits.

PMID- 29053011
TI  - [Articles of the Hungarian Medical Journal from October, 2000].

PMID- 29053012
TI  - The ratio of thioredoxin/Keap1 protein level is a predictor of distant metastasis
      in colorectal cancer.
AB  - AIM: Thioredoxin can reduce the cysteine group of Keap1 which could induce
      proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance
      and Bcl-xL is anti-apoptotic and both are important in tumor progression.
      METHODS: The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal
      and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by
      western blot. RESULTS: The tumor had higher Keap1 but lower PGAM5s and Bcl-xL
      protein expression than the normal tissue. The ratio of thioredoxin/Keap1 protein
      level in the normal (OR: 0.12; 95% CI: 0.02-0.83) or tumor tissue (OR: 0.17; 95%
      CI: 0.03-0.89) was a negative predictor for distant metastasis in CRC.
      CONCLUSION: Keap1-mediated degradation of PGAM5 and Bcl-xL may be active in CRC.
      The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant
      metastasis in CRC.

PMID- 29053013
TI  - Useful strategies for the emerging of Zika pandemic and its silent cardiovascular
      complications.

PMID- 29053014
TI  - Editorial: Assessing cardiovascular risk - should physicians start measuring neck
      circumference?

PMID- 29053015
TI  - Susceptibility biomarker detection in urine exfoliate DNA.
AB  - AIM: The occupational biomonitoring of exposures to carcinogens is carried out by
      measuring dose (metabolites) and susceptibility biomarkers (gene polymorphisms)
      in two biological matrices: urine for metabolite detection and blood for
      genotyping. Blood is the most common substrate but has some disadvantages
      including: invasiveness of the harvesting technique; need of specialized staff
      and equipment; and high infection risk. METHODS & RESULTS: We propose our in
      house approach using urine as single sample in 20 volunteers for simultaneous
      detection of dose and susceptibility biomarkers in order to verify efficacy and
      feasibility. CONCLUSION: Despite the low number of subjects, interindividual and
      gender variability in DNA yield, urine genomic DNA is a valuable source for gene
      polymorphism studies when blood samples are not available. [Formula: see text].

PMID- 29053019
TI  - [Articles of the Hungarian Medical Journal from February, 2000].

PMID- 29053018
TI  - Genetic association of polymorphisms in AXIN1 gene with clear cell renal cell
      carcinoma in a Chinese population.
AB  - AIM: The purpose of the present study is to investigate the association between
      the polymorphisms in AXIN1 with susceptibility to clear cell renal cell carcinoma
      (ccRCC). MATERIALS & METHODS:  A total of 284 ccRCC patients and 439 healthy
      volunteers were enrolled. Totally three tag single nucleotide polymorphisms in
      AXIN1 gene were genotyped using PCR & restriction fragment length polymorphism.
      RESULTS: Significantly increased ccRCC risk was observed to be associated with
      the CT/CC genotypes of rs1805105 and AA genotype of rs12921862. Patients carrying
      the rs1805105 CT genotype had a 1.92-fold increased risk to developing clinical
      stage III and IV cancer. CONCLUSION: Our results suggested the rs1805105 CT/CC
      genotypes and rs12921862 AA genotype may relate to ccRCC development.

PMID- 29053016
TI  - Sudden death: Neurogenic causes, prediction and prevention.
AB  - Sudden death is a major health problem all over the world. The most common causes
      of sudden death are cardiac but there are also other causes such as neurological
      conditions (stroke, epileptic attacks and brain trauma), drugs, catecholamine
      toxicity, etc. A common feature of all these diverse pathologies underlying
      sudden death is the imbalance of the autonomic nervous system control of the
      cardiovascular system. This paper reviews different pathologies underlying sudden
      death with emphasis on the autonomic nervous system contribution, possibilities
      of early diagnosis and prognosis of sudden death using various clinical markers
      including autonomic markers (heart rate variability and baroreflex sensitivity),
      present possibilities of management and promising prevention by electrical
      neuromodulation.

PMID- 29053020
TI  - Cardiovascular outcomes for patients with symptomatic peripheral artery disease:
      A cohort study in The Health Improvement Network (THIN) in the UK.
AB  - Background Few data are available on risk factors and associations with outcomes
      in symptomatic peripheral artery disease (PAD) populations in primary care. We
      assessed characteristics and cardiovascular outcomes in patients with and those
      without symptomatic peripheral artery disease in UK primary care, and quantified
      risk factors for cardiovascular outcomes in patients with peripheral artery
      disease. Methods Among patients in The Health Improvement Network (THIN) aged 50
      89 years in 2000-2010, a symptomatic peripheral artery disease cohort ( n =
      28,484) and a matched comparison cohort without peripheral artery disease ( n =
      113,940) were identified using Read codes. Cox proportional hazard ratios (HRs)
      and 95% confidence intervals (CIs) for cardiovascular outcomes were calculated,
      adjusted for potential confounders. Results The incidence of all-cause death per
      1000 person-years was 83.22 and 50.46 in the peripheral artery disease and non
      peripheral artery disease cohort, respectively (HR 1.41; 95% CI 1.68-1.43). The
      incidence of composite cardiovascular outcome (myocardial infarction, ischaemic
      stroke or cardiovascular-related death) per 1000 person-years was 31.87 and 14.63
      in the peripheral artery disease and non-peripheral artery disease cohort,
      respectively (HR 1.71; 95% CI 1.65-1.77). Risk factors for composite
      cardiovascular outcome in patients with peripheral artery disease were older age
      (>=75 years vs. 50-64 years: HR 2.37; 95% CI 2.20-2.55), current smoking (1.26;
      1.17-1.35), comorbid diabetes (1.42; 1.32-1.52), heart failure (1.31; 1.20-1.44),
      atrial fibrillation (1.32; 1.18-1.47, previous myocardial infarction (1.29; 1.20
      1.39) and previous ischaemic stroke (1.77; 1.63-1.93). Conclusion Patients with
      symptomatic peripheral artery disease in a clinical practice population have a
      high risk of death and cardiovascular-related outcomes. Minimising risk is
      important in the ongoing management of these patients.

PMID- 29053021
TI  - Developing an integrated strategy for evidence generation.

PMID- 29053022
TI  - Analyses and interpretation of cannabis use among NHANES adults.

PMID- 29053023
TI  - N-Acetylcysteine for Nonsuicidal Self-Injurious Behavior in Adolescents: An Open
      Label Pilot Study.
AB  - BACKGROUND: Nonsuicidal self-injury (NSSI) is common in adolescents and young
      adults, and few evidence-based treatments are available for this significant
      problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that
      has been studied in some psychiatric disorders relevant to NSSI including mood
      and addictive disorders. This pilot study tested the use of NAC as a potential
      treatment for NSSI in youth. METHODS: Thirty-five female adolescents and young
      adults with NSSI aged 13-21 years were enrolled in this study that had an open
      label, single-arm study design. All participants were given oral NAC as follows:
      600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg
      twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial,
      at which time youth reported the frequency of NSSI episodes. Levels of
      depression, impulsivity, and global psychopathology were measured at baseline and
      at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt
      Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). RESULTS: About two-thirds
      of the enrolled female youth completed the trial (24/35). NAC was generally well
      tolerated in this sample. NAC treatment was associated with a significant
      decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also
      found that depression scores and global psychopathology scores (but not
      impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not
      correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be
      independent effects. CONCLUSION: We provide preliminary evidence that NAC may
      have promise as a potential treatment option for adolescents with NSSI. The
      current results require follow-up with a randomized, placebo-controlled trial to
      confirm efficacy.

PMID- 29053024
TI  - Early Identification of Bronchopulmonary Dysplasia Using Novel Biomarkers by
      Proteomic Screening.

PMID- 29053025
TI  - E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving
      Increased Neutrophilic Activation and Altered Mucin Secretion.
AB  - RATIONALE: E-cigarettes have become increasingly popular and little is known
      about their potential adverse health effects. OBJECTIVES: To determine the
      effects of e-cigarette use on the airways. METHODS: Induced sputum samples from
      cigarette smokers, e-cigarette users, and nonsmokers were analyzed by
      quantitative proteomics, and the total and individual concentrations of mucins
      MUC5AC and MUC5B were determined by light scattering/refractometry and labeled
      mass spectrometry, respectively. Neutrophil extracellular trap (NET) formation
      rates were also determined for the same groups. MEASUREMENTS AND MAIN RESULTS: E
      cigarette users exhibited significant increases in aldehyde-detoxification and
      oxidative stress-related proteins associated with cigarette smoke compared with
      nonsmokers. The levels of innate defense proteins associated with chronic
      obstructive pulmonary disease, such as elastase and matrix metalloproteinase-9,
      were significantly elevated in e-cigarette users as well. E-cigarette users'
      sputum also uniquely exhibited significant increases in neutrophil granulocyte
      related and NET-related proteins, such as myeloperoxidase, azurocidin, and
      protein-arginine deiminase 4, despite no significant elevation in neutrophil cell
      counts. Peripheral neutrophils from e-cigarette users showed increased
      susceptibility to phorbol 12-myristate 13-acetate-induced NETosis. Finally, a
      compositional change in the gel-forming building blocks of airway mucus (i.e., an
      elevated concentration of mucin MUC5AC) was observed in both cigarette smokers
      and e-cigarette users. CONCLUSIONS: Together, our results indicate that e
      cigarette use alters the profile of innate defense proteins in airway secretions,
      inducing similar and unique changes relative to cigarette smoking. These data
      challenge the concept that e-cigarettes are a healthier alternative to
      cigarettes.

PMID- 29053027
TI  - Editorial.

PMID- 29053026
TI  - Application of "Omics" and Systems Biology to Sarcoidosis Research.
AB  - Sarcoidosis is a complex, polygenic disease of unknown cause with diverse
      clinical phenotypes, ranging from self-limited, asymptomatic disease to life
      altering symptoms and early disease-related mortality. It is unlikely that a
      single common environmental exposure (e.g., infection, antigen) entirely explains
      the disease, and numerous genetic mutations are associated with the disease. As
      such, it is reasonable to assume, as with other phenotypically diverse diseases,
      that distinct genetic mechanisms and related biological biomarkers will serve to
      further define sarcoidosis subphenotypes, mechanisms, and possibly etiology, thus
      guiding personalized care. The fields of "omics" and systems biology research are
      widely applied to understand polygenic and phenotypically diverse diseases, such
      as sarcoidosis. "Omics" refers to technologies that allow comprehensive profiling
      of sets of molecules in an organism. Systems biology applies advanced
      computational approaches to make sense of the enormous data sets that are
      typically generated from "omics" platforms. The primary objectives of this
      article are to review the available "omics" tools, assess the current status of
      "omics" and systems biology research in the field of sarcoidosis, and consider
      how this technology could be applied to advance our understanding of the
      mechanistic underpinnings of disease and to develop novel treatments.

PMID- 29053028
TI  - Product of the neurotrauma symposium 2015.

PMID- 29053029
TI  - The evidence on effectiveness of weekly vs triweekly cisplatin concurrent with
      radiotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC): a
      systematic review and meta-analysis.
AB  - OBJECTIVE: This study aims to synthesize the current available evidences on the
      effectiveness of weekly vs triweekly cisplatin concurrent with radiotherapy in
      the primary and adjuvant treatment of locally advanced head and neck squamous
      cell carcinoma (HNSCC). METHODS: A systematic review and meta-analysis of
      literature were undertaken to assess the effectiveness of weekly vs triweekly
      schedule in primary and adjuvant treatment for HNSCC with adverse risk features.
      Search of relevant articles from electronic database from 2000 to March 2016 and
      appraisal of studies were done. RESULTS: Only one randomized controlled trial
      (RCT) and six retrospective studies were included in this review. The RCT showed
      less severe mucositis (75 vs 38.5%, p = 0.012) and more patients receiving at
      least 200 mg/m2 (62.5% vs 88.5%, p = 0.047) of cisplatin in triweekly arm. There
      was no difference in 1-year progression-free survival (60% vs 71.1%, p = 0.806)
      and 1-year overall survival (OS) (71.6 vs 79.3%, p = 0.978) between the weekly
      and triweekly arm. Pooling of data from six studies showed no difference in 5
      year progression-free survival (RR 0.84, 95%, CI 0.67-1.07), 5-year OS (RR 0.88,
      95% CI 0.73-1.07), severe renal events (RR 0.66, 95% CI 0.42-1.04), severe
      mucositis (RR 0.92, 95% CI 0.71-1.21), severe dermatitis (RR 0.61, 95% CI 0.37
      1.03), treatment interruptions (RR 1.06, 95% CI 0.74-1.52) and number of patients
      receiving at least 200 mg/m2 (RR 0.83, 95% CI 0.67-1.03). CONCLUSION: The current
      evidence showed that weekly schedule is not superior to triweekly in improving
      oncological outcomes and decreasing early effects of treatment. In the absence of
      compelling data, triweekly schedule should remain the standard of care while more
      RCTs are warranted. Advances in knowledge: While some have proposed that low-dose
      weekly cisplatin is safer and less toxic, this study emphasized that there is no
      difference in acute toxicity of the two schedules and it is safe to utilize high
      dose cisplatin every 3 weeks to reach the threshold dose of 200 mg/m2 faster.
      Uniquely, this study excluded nasopharyngeal cancer patients as the biology and
      treatment response are different with other HNSCC.

PMID- 29053031
TI  - Protocol-based management in orbital retinoblastoma.

PMID- 29053030
TI  - A rare case of orbital granulomatous inflammation from explosive hydraulic oil
      masquerading as orbital cellulitis.
AB  - The differential diagnosis for acute orbital inflammation is broad. We report a
      case of granulomatous orbital inflammation due to high-pressure oil injury to the
      orbit presenting as an atypical orbital cellulitis. Here we review the
      presentation and treatment of orbital inflammation from oil.

PMID- 29053032
TI  - A mouse model of subcortical vascular dementia reflecting degeneration of
      cerebral white matter and microcirculation.
AB  - Subcortical vascular dementia(SVaD) is associated with white matter damage,
      lacunar infarction, and degeneration of cerebral microcirculation. Currently
      available mouse models can mimic only partial aspects of human SVaD features.
      Here, we combined bilateral common carotid artery stenosis (BCAS) with a
      hyperlipidaemia model in order to develop a mouse model of SVaD; 10- to 12-week
      old apolipoprotein E (ApoE)-deficient or wild-type C57BL/6J mice were subjected
      to sham operation or chronic cerebral hypoperfusion with BCAS using micro-coils.
      Behavioural performance (locomotion, spatial working memory, and recognition
      memory), histopathological findings (white matter damage, microinfarctions,
      astrogliosis), and cerebral microcirculation (microvascular density and blood
      brain barrier (BBB) integrity) were investigated. ApoE-deficient mice subjected
      to BCAS showed impaired locomotion, spatial working memory, and recognition
      memory. They also showed white matter damage, multiple microinfarctions,
      astrogliosis, reduction in microvascular density, and BBB breakdown. The
      combination of chronic cerebral hypoperfusion and ApoE deficiency induced
      cognitive decline and cerebrovascular pathology, including white matter damage,
      multiple microinfarctions, and degeneration of cerebral microcirculation.
      Together, these features are all compatible with those of patients with SVaD.
      Thus, the proposed animal model is plausible for investigating SVaD
      pathophysiology and for application in preclinical drug studies.

PMID- 29053033
TI  - Hyaluronidase allergy mimicking orbital cellulitis.
AB  - PURPOSE: Hyaluronidase enzyme is a common additive with local anesthetic agent to
      facilitate faster permeation of the anesthetic in periocular tissues during
      ophthalmic surgery. We report a series of five subjects presenting with clinical
      features mimicking orbital cellulitis following peribulbar anesthesia and
      consequently diagnosed with hyaluronidase hypersensitivity. SETTING: The study
      was conducted at a tertiary eye care center in Southern India. DESIGN: It was a
      retrospective interventional case series. METHODS: We retrospectively reviewed
      the case records of patients diagnosed as and treated for hyaluronidase allergy
      from 2011 to 2015. The presenting features included periocular edema, proptosis,
      and restriction of ocular movements. The symptoms appeared immediately after the
      injection to as late as 6 days after the surgery. All patients underwent
      comprehensive ophthalmic evaluation, relevant investigations, and dermal allergy
      tests. All five patients tested positive for hyaluronidase. Patients were treated
      with antihistaminics, systemic steroids, and emergency orbital decompression,
      when required. In majority of the patients, symptoms resolved in 3-5 days.
      Clinically, hyaluronidase allergy may mimic orbital cellulitis, which in the
      context of a recent intraocular surgery may be alarming for both the patient and
      the surgeon. However, with prompt intervention, the prognosis is extremely
      favorable in cases of hyaluronidase allergy. It is important for ophthalmic
      surgeons and anesthetists to recognize and differentiate this entity from the
      more serious vision threatening conditions.

PMID- 29053034
TI  - Circadian rest-activity rhythm in chronic obstructive pulmonary disease.
AB  - To characterize circadian rest-activity rhythm in COPD, 26 cases (66.9 +/- 8.5y)
      and 15 controls (63.0 +/- 10.7y) were assessed by actimetry. Rhythm fragmentation
      was measured by intradaily variability (IV), while synchronization to the 24-h
      light-dark cycle was measured by interdaily stability (IS). The average activity
      during the least active 5-h period (L5) and the average activity during the most
      active 10-h period (M10) were used to calculate the relative amplitude mean [RAm
      = (M10-L5)/(M10+L5)]. COPD patients presented higher IVm (0.242 +/- 0.097 vs
      0.182 +/- 0.063) and L5 (36.849 +/- 18.239 vs 19.888 +/- 12.268) and lower RAm
      (0.696 +/- 0.134 vs 0.833 +/- 0.093) than controls. Future studies on the effects
      of chronotherapy measures in COPD are warranted.

PMID- 29053035
TI  - Alpha-synuclein levels in patients with multiple system atrophy: a meta-analysis.
AB  - PURPOSE: This study evaluates the relationship between multiple system atrophy
      and alpha-synuclein levels in the cerebrospinal fluid, plasma and neural tissue.
      METHOD: Literature search for relevant research articles was undertaken in
      electronic databases and study selection was based on a priori eligibility
      criteria. Random-effects meta-analyses of standardized mean differences in alpha
      synuclein levels between multiple system atrophy patients and normal controls
      were conducted to obtain the overall and subgroup effect sizes. Meta-regression
      analyses were performed to evaluate the effect of age, gender and disease
      severity on standardized mean differences. RESULTS: Data were obtained from 11
      studies involving 378 multiple system atrophy patients and 637 healthy controls
      (age: multiple system atrophy patients 64.14 [95% confidence interval 62.05,
      66.23] years; controls 64.16 [60.06, 68.25] years; disease duration: 44.41
      [26.44, 62.38] months). Cerebrospinal fluid alpha-synuclein levels were
      significantly lower in multiple system atrophy patients than in controls but in
      plasma and neural tissue, alpha-synuclein levels were significantly higher in
      multiple system atrophy patients (standardized mean difference: -0.99 [-1.65, 
      0.32]; p = 0.001). Percentage of male multiple system atrophy patients was
      significantly positively associated with the standardized mean differences of
      cerebrospinal fluid alpha-synuclein levels (p = 0.029) whereas the percentage of
      healthy males was not associated with the standardized mean differences of
      cerebrospinal fluid alpha-synuclein levels (p = 0.920). CONCLUSION: In multiple
      system atrophy patients, alpha-synuclein levels were significantly lower in the
      cerebrospinal fluid and were positively associated with the male gender.

PMID- 29053036
TI  - Eyelid syringocystadenoma papilliferum: A novel presentation with major review.
AB  - A major review of the literature of syringocystadenoma papilliferum's (SCAP's)
      presentation and management is presented. In addition, a case report of this
      unique diagnosis presenting as a corneal abrasion in a 66-year-old-male is
      included. This benign adnexal tumor of the apocrine glands is most commonly found
      in the face and neck. When found on the eyelids, these lesions are commonly
      misdiagnosed as basal cell carcinoma or cysts. Diagnosis is made based on
      histopathology. Treatment is complete excision of the lesion and this has a low
      recurrence rate. While predominantly benign, there have been cases of basal cell
      carcinoma development or other malignant transformations. Of the 26 reported
      cases of SCAP of the eyelids, none have caused a corneal abrasion. The authors
      present the only known presentation of eyelid SCAP, causing corneal abrasions,
      and provide a review of literature with discussion of clinical presentation,
      natural history, diagnosis, and treatment of this rare, eyelid lesion with
      potential for malignant transformation.

PMID- 29053037
TI  - Possible autoantibody-negative limbic encephalitis after anterior temporal
      lobectomy for hippocampal sclerosis.
AB  - PURPOSE: Amnestic syndromes are acknowledged to be associated to bilateral
      hippocampal damage. MATERIALS AND METHODS: We briefly report the case of a young
      man who underwent anterior left temporal lobectomy for a medically refractory
      temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and
      neuropsychological outcome. Approximately 10 years later, he presented with a
      subacute severe global amnesia and neuroimaging findings of a damage involving
      the contralateral mesial temporal lobe structures. RESULTS: A diagnosis of a
      possible autoimmune encephalitis was made. CONCLUSIONS: Due to its peculiarities
      (compared with other cases of bilateral temporal lesions, the damage occurred on
      two distinct occasions), this case might contribute to shed light on the issue of
      the possible contralateral reorganization of memory processes subserved by the
      mesial temporal lobe structures chronically involved in epileptogenesis.

PMID- 29053039
TI  - The First Time I Met Her.

PMID- 29053038
TI  - IgG4-related orbital disease masquerading as thyroid eye disease, vice versa, or
      both?
AB  - A 40 year-old male presented after one year of unilateral, progressive, steroid
      responsive, orbital inflammatory disease causing proptosis, extraocular muscle
      (EOM) restriction, and compressive optic neuropathy. The development of anti
      thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED);
      however, the prolonged active phase, remarkable reversibility of ophthalmic
      features with high-dose corticosteroids, unilaterally of disease,
      uncharacteristic EOM involvement (including both obliques), and the absence of
      autoimmune thyroid disease provoked consideration of alternative diagnoses.
      Inferior oblique biopsy stained positive for IgG4 with histologic features
      atypical of TED. The patient received rituximab for presumed IgG4-related orbital
      disease (IgG4-ROD) with subsequent reversal of compressive optic neuropathy, near
      complete resolution of EOM restriction, and improved proptosis, the latter two of
      which are not routinely anticipated in advanced TED. The possible role for B-cell
      depletion in both TED and IgG4-ROD suggests a degree of overlap in the underlying
      immune-related pathophysiology that is yet to be defined.

PMID- 29053040
TI  - Intraconal gauze mass: An unusual complication of orbital fracture repair - a
      case report.
AB  - Gossypiboma and textiloma are terms used to describe tumor-like masses caused by
      retained gauze or surgical sponges after any operation. It is a rare surgical
      complication, usually difficult to diagnose due to its variable clinical
      presentation and nonstandard radiological appearance. We describe here a rare
      case of orbital gossypiboma in a child after surgical correction of an orbital
      blowout fracture.

PMID- 29053041
TI  - Scleral contact lenses for the management of complicated ptosis.
AB  - PURPOSE: To present the management of three patients suffering from ptosis of
      various etiologies, with scleral contact lenses. MATERIAL AND METHODS: Three
      patients (five eyes) with ptosis resulting from levator dehiscence due to long
      term rigid gas permeable contact lens wear for keratoconus, phthisis bulbi, and
      myopathy due to Kearns-Sayre syndrome were identified during a 2-year period.
      They were fitted with scleral contact lenses in order to provide cosmesis by
      lifting the upper eyelid with the bulk of the lens, and simultaneously provide
      vision correction where applicable. RESULTS: The scleral contact lenses provided
      comfortable wear, significantly improved cosmesis as both palpebral aperture and
      marginal reflex distance were increased, and visual acuity was also subjectively
      and objectively improved. Two of the patients opted for the scleral contact
      lenses, whereas the parents of the third patient, a 10-year-old girl with Kearns
      Sayre syndrome, chose to undergo ptosis surgery due to handling issues of the
      scleral contact lenses. CONCLUSION: Scleral contact lenses can be a useful
      addition to the treatment option for patients with complicated ptosis.

PMID- 29053042
TI  - Paper incompletely describes evidence-based usage of probiotics.

PMID- 29053043
TI  - Entropion and ectropion repair: a snapshot of surgical practice in the United
      Kingdom.
AB  - We aim to provide a snapshot of the current surgical practice for correction of
      entropion and ectropion, the two most common oculoplastic procedures carried out
      in the UK, by surveying 135 consultant oculoplastic surgeons via the tool Survey
      Monkey. Forty-seven (35%) consultants responded. For entropion, 44% of surgeons
      opted for lateral tarsal strip (LTS) + everting sutures (ES). Other first-line
      choices included LTS + transcutaneous retractor plication (21%), Quickert's
      procedure (14%), ES (7%), and Wies procedure (5%). Important patient-related
      factors to consider were horizontal lid laxity and retractor dehiscence.
      Regarding ectropion, LTS was most commonly practiced (35%), followed by LTS +
      transconjunctival retractor plication (28%), wedge excision (16%), and lateral
      canthoplasty (5%). The patient-related factors guiding choice were horizontal lid
      laxity, lateral canthal tendon laxity, and punctal position under traction.
      Responses found a wide range of preferred surgical techniques in practice. The
      factors guiding surgical choice were personal audit results (92% stated
      important/very important), familiarity with the technique (92%), and the
      technique being favoured by previous trainers (76%), suggesting current practice
      led by expert opinion, possibly due to a lack of evidence-based literature. This
      highlights the variety of core oculoplastic surgical techniques practiced and
      underlines the need for robust trials to guide surgical choice.

PMID- 29053044
TI  - Superior ophthalmic vein thrombosis: A rare complication of Graves' orbitopathy.
AB  - Superior ophthalmic vein thrombosis is a rare, life- and sight-threatening
      complication of both infectious and inflammatory orbital disease as well as
      hypercoagulable state. Only one case of superior ophthalmic vein thrombosis due
      to thyroid eye disease has been reported in the literature. This article
      describes the diagnosis and management of a case of superior ophthalmic vein
      thrombosis due to Graves' orbitopathy. Early diagnosis is critical to facilitate
      timely therapeutic intervention. Superior ophthalmic vein thrombosis should be
      considered in the differential diagnosis of acute on chronic proptosis in the
      setting of Graves' orbitopathy, and may represent and under-recognized and under
      diagnosed clinical entity.

PMID- 29053045
TI  - Relationship between ocular dominance and brow position in patients with
      blepharoptosis.
AB  - PURPOSE: This study aims to determine if ocular dominance plays a role in
      predicting compensatory eyebrow elevation in cases of ptosis. METHODS: This
      retrospective observational cohort study screened all individuals presenting to
      two tertiary oculoplastics practices with complaints of ptosis for entry. Primary
      position photographs were obtained. Ocular dominance was assessed via a modified
      Porta test. Ptosis was defined in bilateral cases as marginal reflex distance of
      <2.5 mm in both eyes and in unilateral cases as either an MRD1 < 2.5 mm or MRD1
      of >1 mm lower on one side. Asymmetry in brow height was defined as a difference
      of >1 mm. Chi square and t-tests were performed. RESULTS: Sixty-eight patients
      from the both tertiary practices met inclusion criteria (37 male, 31 female).
      Concordance between the higher brow and the dominant side was 50.0% (n = 22, p >
      0.05). Mean brow height on the dominant side (15.5 mm) was not statistically
      different than brow height on the non-dominant side (15.3 mm, p > 0.05). The
      concordance between the higher brow and the lower MRD1 eyelid was not significant
      (45.5%, n = 20, p > 0.05). The difference in mean brow height between the lower
      and higher MRD1 eyes was not significantly different (-0.11 mm; p > 0.05). This
      also held true when restricted to unilateral cases (0.28; p > 0.05). CONCLUSIONS:
      Although asymmetric brow elevation can be noted in patients with ptosis, ocular
      dominance does not appear to be concordant with this asymmetry. Additionally,
      brow height does not appear to be concordant with MRD1 in cases of ptosis.

PMID- 29053046
TI  - Microcystic adnexal carcinoma of the orbit mimicking pagetoid sebaceous gland
      carcinoma.
AB  - Microcystic adnexal carcinoma (MAC) is a rare malignancy of sweat glands that has
      been reported most often on the face in the form of a cutaneous lesion, with the
      potential for deeper invasion. The synonyms of MAC include sclerosing sweat duct
      carcinoma, syringomatous carcinoma, and malignant syringoma. Clinically, MAC in
      the periocular area has been misdiagnosed as basal cell carcinoma, squamous cell
      carcinoma, or even chalazia. We report a case of MAC presenting clinically as
      sebaceous gland carcinoma with pagetoid spread for the first time in literature.

PMID- 29053047
TI  - Perineural spread of basosquamous carcinoma to the orbit, cavernous sinus, and
      infratemporal fossa.
AB  - Basosquamous carcinoma is a rare, highly aggressive variant of basal cell
      carcinoma with elevated rates of recurrence, perineural invasion, and metastasis.
      We describe a patient who presented with unilateral complete ophthalmoplegia,
      ptosis, optic neuropathy, and trigeminal neuropathy due to perineural
      intracranial invasion of nasal basosquamous carcinoma via the sphenopalatine
      fossa to the cavernous sinus, orbit, and infratemporal fossa. To our knowledge,
      this is the first reported case of basosquamous carcinoma with perineural
      invasion involving the cavernous sinus in the English language ophthalmic
      literature. Physicians should be aware of the diagnostic features, clinical
      challenges and aggressive nature of basosquamous carcinoma, a rare diagnosis that
      can lead to significant morbidity/mortality when left unrecognized.

PMID- 29053049
TI  - A Bayesian Meta-analysis Method for Estimating Risk Difference of Rare Events.
AB  - Bayesian meta-analysis has been more frequently utilized for synthesizing safety
      and efficacy information to support landmark decision-making due to its
      flexibility of incorporating prior information and availability of computing
      software. However, when the outcome is binary and the events are rare, where
      event counts can be zero, conventional meta-analysis methods including Bayesian
      methods may not work well. Several methods have been proposed to tackle this
      issue but the prior knowledge of event rate was not utilized to increase
      precision of risk difference estimates. To better estimate risk differences, we
      propose a new Bayesian method, Beta prior BInomial model for Risk Differences (B
      BIRD), which takes into account the prior information of rare events. B-BIRD is
      illustrated using a real data set of 48 clinical trials about a type 2 diabetes
      drug. In simulation studies, it performs well in low event rate settings.

PMID- 29053048
TI  - Neurofibromatosis type 1: A neuro-psycho-cutaneous syndrome?
AB  - Neurofibromatosis type 1 (NF1) is an inherited disorder often associated with
      optic nerve gliomas, low-grade brain tumors, and readily visible signs. Though
      these features are frequently emphasized, the psychosocial and emotional
      morbidities are often overlooked. We present a patient with depressive disorder
      resulting in suicide in a patient with NF1.

PMID- 29053050
TI  - Down-Time During Work-Time.
AB  - An idle body can harbor an idle mind that often brews something appalling in
      emptiness. Refreshing one's mind during Down-Time (Me-Time) with "harmless"
      activities is a must whether at home or at the workplace.

PMID- 29053051
TI  - Photobiomodulation Therapy Alleviates Tissue Fibroses Associated with Chronic
      Graft-Versus-Host Disease: Two Case Reports and Putative Anti-Fibrotic Roles of
      TGF-beta.
AB  - OBJECTIVE: Patients who receive allogeneic hematopoietic stem cell
      transplantation may experience oral complications due to chronic graft-versus
      host disease (cGVHD). The manifestations may include progressive sclerosis-like
      changes that may involve various body sites, including the oropharynx. METHODS
      AND RESULTS: We present two cGVHD cases of oropharyngeal fibrotic changes that
      affected functions that were treated with photobiomodulation (PBM) therapy. These
      case reports suggest that PBM therapy represents an additional, innovative
      approach affecting discrete phases in cGVHD-associated fibrotic changes.
      CONCLUSIONS: We discuss these observations in the context of currently understood
      molecular mechanisms, especially induction of transforming growth factor beta and
      NFkappaB that appear to be counter-intuitive to their known roles in matrix
      synthesis and inflammation that contribute to tissue fibroses. The clinical
      benefit noted in the two cases presented clearly indicates that there are
      distinct mechanistic and biological insights in the regulation of these molecular
      pathways in determining therapeutic efficacy with PBM therapy.

PMID- 29053052
TI  - Effect of Laser Etching on Glass Fiber Posts Cemented with Different Adhesive
      Systems.
AB  - BACKGROUND: Glass fiber-reinforced posts have been preferred frequently because
      of some physical properties similar to the dentin, chemically bonding to dentin,
      biocompatibility, and esthetics. OBJECTIVE: This study aimed to evaluate the
      microleakage and bond strength of glass fiber posts cemented with various
      adhesive systems on laser-etched root canal walls. METHODS: Roots of 120 human
      mandibular premolars were divided into two groups for push-out bond strength test
      and the microleakage test (n = 60). Erbium-doped yttrium-aluminum-garnet (Er:YAG)
      laser etching of the root canal walls was carried out on half of the specimens in
      both test groups. The laser-treated and laser-nontreated groups were divided
      again into three subgroups (n = 10). Glass fiber posts (everStick Post) were
      luted using three different resin cements: total-etch (Variolink N), self-etch
      (Panavia F 2.0), and self-adhesive (Rely X Unicem). Three dentin discs were
      obtained from each root, and the bond strength of the glass fiber posts was
      measured by push-out tests. The dye penetration method was used to investigate
      coronal microleakage. In addition, surface treatments and the bonding interfaces
      were observed using scanning electron microscope. RESULTS: The highest bond
      strengths were observed for the total-etch and self-adhesive resin cement groups
      with laser etching (p < 0.05), and the lowest bond strength was obtained for the
      self-etch resin cement group (p < 0.05). There were no statistically significant
      differences in terms of microleakage (p > 0.05), except for the self-adhesive
      resin cement group (p < 0.05). CONCLUSIONS: Er:YAG laser etching enhances the
      bonding strength of glass fiber posts. In addition, laser etching can reduce
      microleakage of self-adhesive resin cement.

PMID- 29053053
TI  - Methylene Chloride.
AB  - Methylene chloride is an industrial solvent used in commercial paint strippers
      and degreasing agents. This chemical is widely used in consumer products, yet
      without appropriate protections, exposure may lead to death. Already banned in
      some countries, the Environmental Protection Agency (EPA) recently proposed
      limiting its use in the United States.

PMID- 29053055
TI  - Successful surgical repair and recovery in a 2-week-old infant after birth
      related cervical fracture dislocation.
AB  - Cervical spine injuries are the most common spine injuries in the pediatric
      population. The authors present the youngest known patient who underwent cervical
      spine fusion to repair birth trauma-induced cervical fracture dislocation,
      resulting in spondyloptosis and spinal cord injury. A 2-week-old boy was found to
      have spondyloptosis and spinal cord injury after concerns arose from reduced
      movement of the extremities. The patient's birth was complicated by undiagnosed
      abdominal dystocia, which led to cervical distraction injury. At 15 days of age,
      the boy underwent successful C-5 corpectomy, with anterior C4-6 and posterior C2
      7 arthrodesis, using an autologous rib graft for a C-5 fracture dislocation. MRI
      performed 2 weeks postoperatively revealed significant improvement in the
      alignment of the spinal canal. The patient was discharged from the hospital in a
      custom Minerva brace and underwent close follow-up in addition to occupational
      therapy and physical therapy. At the latest follow-up 4.5 years later, the
      patient was able to walk and ride a tricycle by himself. The authors describe the
      patient's surgery and the challenges faced in achieving successful repair and
      cervical spine stabilization in such a young patient. The authors suggest that
      significant neurological recovery after spinal cord injury in infants is possible
      with appropriate, timely, and interdisciplinary management.

PMID- 29053056
TI  - Intradural spine surgery may not carry an increased risk of shunt revision
      compared with extradural spine surgery in pediatric patients with
      myelomeningocele.
AB  - OBJECTIVE Patients with myelomeningocele are often affected by scoliosis and
      tethered cord syndrome, and frequently require spine surgery. Intradural spine
      surgeries may carry an inherently higher risk of inducing shunt malfunction due
      to entry into the subarachnoid space. In this study, the authors sought to
      compare rates of shunt malfunction after intradural and extradural spine
      surgeries among pediatric patients with myelomeningocele. METHODS The authors
      reviewed records of the National Spina Bifida Program Registry for Children's
      Hospital of Alabama. The Exago reporting function was used to identify patients
      who had received at least one of the following procedures: shunt revision,
      tethered cord release (TCR), or spinal fusion for deformity. The registry records
      were reviewed for all identified patients to determine if a shunt revision was
      performed within the 1st year after TCR or spinal fusion. RESULTS Final analyses
      included 117 patients, of whom 39 underwent spinal fusion and 78 underwent TCR.
      Among patients who underwent spinal fusion, shunt revision was performed within
      30 days in 2 patients (5.1%), within 60 days in 2 (5.1%), within 90 days in 4
      (10.3%), and within 1 year in 5 (12.8%). Among patients who underwent TCR, shunt
      revision was performed within 30 days in 7 patients (9.0%), within 60 days in 10
      (12.8%), within 90 days in 11 (14.1%), and within 1 year in 17 (21.8%). Using the
      log-rank test, there was no significant difference in Kaplan-Meier curves between
      intradural and extradural groups (p = 0.59). CONCLUSIONS In a review of single
      institution registry data, the authors found no statistically significant
      difference in the risk of shunt malfunction after intradural and extradural spine
      surgeries.

PMID- 29053060
TI  - Editorial policy.

PMID- 29053059
TI  - The sensitivity and specificity of a urine based Rapid Diagnostic Test for the
      diagnosis of plasmodium falciparum in a malaria endemic area in Odisha, India.
AB  - BACKGROUND: Rapid and accurate diagnosis is crucial in the treatment of malaria.
      Rapid Diagnostic Tests (RDTs) using blood have been recommended by the WHO as an
      acceptable method for the diagnosis of malaria. RDTs provide results quickly, is
      simple to use and easy to interpret. However, its use requires collection of
      blood by skin puncture. Hence the aim of the pilot study is to explore the
      sensitivity and specificity of RDTs using urine (collected non-invasively) for
      diagnosis of Plasmodium falciparum malaria and to assess the relation between
      parasite density in blood with HRP-2 Ag detection in urine. MATERIAL AND METHOD:
      All fever cases admitted to Ispat General Hospital (IGH) Rourkela, India, during
      June 2012-March 2013 with a clinical diagnosis of malaria were examined for the
      presence of asexual forms of P. falciparum in peripheral blood smears. All smear
      positive febrile patients who met the eligibility criteria were enrolled. Smear
      negative fever cases were enrolled as control cases. RDTs were performed using
      both urine and blood samples by using commercially available blood specific kits.
      RESULTS: Sixty blood smear positive cases and 51 febrile blood smear negative
      cases were enrolled. Sensitivity and specificity of RDT urine were 86.67%
      (95%CI:75.83-93.09) and 94.12% (95%CI:84.08-97.98) respectively whereas those of
      RDT blood were 91.67% (95% CI: 81.93-96.39) and 98.04% (95% CI 89.7-99.65). The
      sensitivity of both RDT urine as well as RDT blood were found to be dependent on
      the level of parasitemia. CONCLUSION: Results of this study are promising. Larger
      studies are needed to assess whether RDTs using urine could serve as a practical,
      reliable method for the detection of P. falciparum in a non-invasive manner where
      invasive blood taking is less feasible.

PMID- 29053061
TI  - Change of address for journal and business office.

PMID- 29053057
TI  - Communal Coping and Adjustment to Chronic Illness: Theory Update and Evidence.
AB  - We present a theory of communal coping that describes an optimal pathway to
      patient adjustment among couples in which one person faces a chronic illness.
      Communal coping consists of a shared illness appraisal (i.e., person perceives
      illness as a joint rather than individual problem) and collaboration with a
      partner to manage the illness. We present a model of the communal coping process
      that links patient and partner shared illness appraisals to collaboration and a
      set of supportive interactions that might be reframed as collaboration in the
      presence of shared illness appraisals. We then outline a model that identifies
      potential antecedents of communal coping and mechanisms that link communal coping
      to patient illness adjustment (i.e., enhanced psychological well-being, improved
      health behaviors, better physical health) and partner psychological well-being.
      We review the empirical evidence for this model and conclude by identifying
      several moderator variables, noting potential limitations, and outlining future
      research directions.

PMID- 29053063
TI  - A patent review of Monoacylglycerol Lipase (MAGL) inhibitors (2013-2017).
AB  - INTRODUCTION: Monoacylglycerol lipase is a serine hydrolase that plays a major
      role in the degradation of the endocannabinoid 2-arachidonoylglycerol. Because of
      this key role, selective inactivation of MAGL represents an interesting approach
      to obtain desirable effects in several diseases. Furthermore, MAGL is upregulated
      in cancer cells and primary tumors and its inhibition in aggressive breast,
      ovarian, and melanoma cancer cells impairs cell migration, invasiveness, and
      tumorigenicity. Areas covered: This review covers patent literature on MAGL
      inhibitors and their applications published from 2013 to 2017. Expert opinion:
      MAGL inhibition has gained considerable importance in many therapeutic fields and
      one compound has been subjected to Phase I studies. Even if a reasonable number
      of patents have been recently reported, novel MAGL inhibitors are still required,
      especially novel chemical classes displaying a reversible mechanism of action.

PMID- 29053065
TI  - Investigation of the role of alginate containing high guluronic acid on
      osteogenic differentiation capacity of human umbilical cord Wharton's jelly
      mesenchymal stem cells.
AB  - BACKGROUND AND AIM: Cell encapsulation using biodegradable material has promising
      results for tissue engineering. Since pressure is an effective factor on stem
      cell behaviour and various concentrations of alginate create different pressures
      on the cells, therefore our goal was to evaluate the mechanical effect of 1/2%
      (w/v) and 1/8% (w/v) alginate containing high guluronic acid on viability and
      osteogenic capacity of HUCWJ cells. METHODS: Cell viability was evaluated by MTT
      assay after 1, 7 and 14 days. Alkaline phosphatase activity was evaluated by
      alkaline phosphatase assay kit after 14 and 21 days. Alizarin red S staining was
      performed for calcium deposition among histological section. RESULTS: MTT assay
      showed significant difference in the mean of viability rates between groups in
      day 14 (p < 0.05). Alizarin red S staining was higher in the group 1.8%. In
      addition, there was statistically significant higher ALP activity in the group
      1.8% compared to the group 1.2%.

PMID- 29053066
TI  - Different times of day do not change heart rate variability recovery after light
      exercise in sedentary subjects: 24 hours Holter monitoring.
AB  - Incidence of cardiovascular events follows a circadian rhythm with peak
      occurrence during morning. Disturbance of autonomic control caused by exercise
      had raised the question of the safety in morning exercise and its recovery.
      Furthermore, we sought to investigate whether light aerobic exercise performed at
      night would increase HR and decrease HRV during sleep. Therefore, the aim of this
      study was to test the hypothesis that morning exercise would delay HR and HRV
      recovery after light aerobic exercise, additionally, we tested the impact of late
      night light aerobic exercise on HR and HRV during sleep in sedentary subjects.
      Nine sedentary healthy men (age 24 +/- 3 yr; height 180 +/- 5 cm; weight 79 +/- 8
      kg; fat 12 +/- 3%; mean+/-SD) performed 35 min of cycling exercise, at an
      intensity of first anaerobic threshold, at three times of day (7 a.m., 2 p.m. and
      11 p.m.). R-R intervals were recorded during exercise and during short-time (60
      min) and long-time recovery (24 hours) after cycling exercise. Exercise evoked
      increase in HR and decrease in HRV, and different times of day did not change the
      magnitude (p < 0.05 for time). Morning exercise did not delay exercise recovery,
      HR was similar to rest after 15 minutes recovery and HRV was similar to rest
      after 30 minutes recovery at morning, afternoon, and night. Low frequency power
      (LF) in normalized unites (n.u.) decreased during recovery when compared to
      exercise, but was still above resting values after 60 minutes of recovery. High
      frequency power (HF-n.u.) increased after exercise cessation (p < 0.05 for time)
      and was still below resting values after 60 minutes of recovery. The LF/HF ratio
      decreased after exercise cessation (p < 0.05 for time), but was still different
      to baseline levels after 60 minutes of recovery. In conclusion, morning exercise
      did not delay HR and HRV recovery after light aerobic cycling exercise in
      sedentary subjects. Additionally, exercise performed in the night did change
      autonomic control during the sleep. So, it seems that sedentary subjects can
      engage physical activity at any time of day without higher risk.

PMID- 29053067
TI  - The proteome of pus from human brain abscesses: host-derived neurotoxic proteins
      and the cell-type diversity of CNS pus.
AB  - OBJECTIVE What determines the extent of tissue destruction during brain abscess
      formation is not known. Pyogenic brain infections cause destruction of brain
      tissue that greatly exceeds the area occupied by microbes, as seen in
      experimental studies, pointing to cytotoxic factors other than microbes in pus.
      This study examined whether brain abscess pus contains cytotoxic proteins that
      might explain the extent of tissue destruction. METHODS Pus proteins from 20
      human brain abscesses and, for comparison, 7 subdural empyemas were analyzed by
      proteomics mass spectrometry. Tissue destruction was determined from brain
      abscess volumes as measured by MRI. RESULTS Brain abscess volume correlated with
      extracellular pus levels of antibacterial proteins from neutrophils and
      macrophages: myeloperoxidase (r = 0.64), azurocidin (r = 0.61), lactotransferrin
      (r = 0.57), and cathelicidin (r = 0.52) (p values 0.002-0.018), suggesting an
      association between leukocytic activity and tissue damage. In contrast,
      perfringolysin O, a cytotoxic protein from Streptococcus intermedius that was
      detected in 16 patients, did not correlate with abscess volume (r = 0.12, p =
      0.66). The median number of proteins identified in each pus sample was 870 (range
      643-1094). Antibiotic or steroid treatment prior to pus evacuation did not reduce
      the number or levels of pus proteins. Some of the identified proteins have well
      known neurotoxic effects, e.g., eosinophil cationic protein and nonsecretory
      ribonuclease (also known as eosinophil-derived neurotoxin). The cellular response
      to brain infection was highly complex, as reflected by the presence of proteins
      that were specific for neutrophils, eosinophils, macrophages, platelets,
      fibroblasts, or mast cells in addition to plasma and erythrocytic proteins. Other
      proteins (neurofilaments, myelin basic protein, and glial fibrillary acidic
      protein) were specific for brain cells and reflected damage to neurons,
      oligodendrocytes, and astrocytes, respectively. Pus from subdural empyemas had
      significantly higher levels of plasma proteins and lower levels of leukocytic
      proteins than pus from intracerebral abscesses, suggesting greater turnover of
      the extracellular fluid of empyemas and washout of pus constituents. CONCLUSIONS
      Brain abscess pus contains leukocytic proteins that are neurotoxic and likely
      participate actively in the excessive tissue destruction inherent in brain
      abscess formation. These findings underscore the importance of rapid evacuation
      of brain abscess pus.

PMID- 29053068
TI  - Suprafloccular approach via the petrosal fissure and venous corridors for
      microvascular decompression of the trigeminal nerve: technique notes and clinical
      outcomes.
AB  - OBJECTIVE Surgical exposure and decompression of the entire trigeminal nerve in a
      conventional lateral supracerebellar approach can be challenging because of
      blockages from the superior petrosal vein complex, cerebellum, and
      vestibulocochlear nerve. The authors demonstrate a novel suprafloccular approach
      via the petrosal fissure and venous corridors that can be used as a substitute
      for the conventional route used to treat trigeminal neuralgia and present a
      consecutive series of patients and their clinical outcomes. METHODS Preoperative
      and postoperative clinical data from 420 patients who underwent this modified
      approach at Hangzhou First People's Hospital between March 2012 and May 2014 were
      reviewed. The technique expands the working space by opening the petrosal fissure
      and dissecting adhesions between the vein of the cerebellopontine fissure and the
      simple lobule as needed. Via 3 surgical corridors, the entire trigeminal nerve is
      exposed and decompressed thoroughly with minimal retraction of the surrounding
      vital structures. RESULTS The medial one-third of the trigeminal nerve accounted
      for the majority (275 [65.5%] cases) of neurovascular conflict sites. The lateral
      corridor was used in 219 (52.1%) cases, the medial corridor was used in 175
      (41.7%) cases, and the intermediate corridor was used in 26 (6.2%) cases. The
      entire trigeminal nerve in each patient was accessed directly and decompressed
      properly. At the end of the 24-month follow-up period, the rate of excellent
      results (Kondo score of T0 or T1) was stable at approximately 90.5%. No
      complications were related directly to petrosal vein or vestibulocochlear nerve
      injury. CONCLUSIONS Based on data from the large patient series, the authors
      found this suprafloccular approach via the petrosal fissure and venous corridors
      provides full exposure and decompression of the entire trigeminal nerve, a high
      cure rate, and a low neurovascular morbidity rate.

PMID- 29053069
TI  - Detection of glioblastoma in biofluids.
AB  - The detection of glioblastoma (GBM) in biofluids offers potential advantages over
      existing paradigms for the diagnosis and therapeutic monitoring of glial tumors.
      Biofluid-based detection of GBM focuses on detecting tumor-specific biomarkers in
      the blood and CSF. Current clinical research concentrates on studying 3 distinct
      tumor-related elements: extracellular macromolecules, extracellular vesicles, and
      circulating tumor cells. Investigations into these 3 biological classifications
      span the range of locales for tumor-specific biomarker discovery, and combined,
      have the potential to significantly impact GBM diagnosis, monitoring for
      treatment response, and surveillance for recurrence. This review highlights the
      recent advancements in the development of biomarkers and their efficacy for the
      detection of GBM.

PMID- 29053070
TI  - Relationship between patient safety indicator events and comprehensive stroke
      center volume status in the treatment of unruptured cerebral aneurysms.
AB  - OBJECTIVE The Agency of Healthcare Research and Quality (AHRQ) has defined
      Patient Safety Indicators (PSIs) for assessments in quality of inpatient care.
      The hypothesis of this study is that, in the treatment of unruptured cerebral
      aneurysms (UCAs), PSI events are less likely to occur in hospitals meeting the
      volume thresholds defined by The Joint Commission for Comprehensive Stroke Center
      (CSC) certification. METHODS Using the 2002-2011 National (Nationwide) Inpatient
      Sample, patients treated electively for a nonruptured cerebral aneurysm were
      selected. Patients were evaluated for PSI events (e.g., pressure ulcers, retained
      surgical item, perioperative hemorrhage, pulmonary embolism, sepsis) defined by
      AHRQ-specified ICD-9 codes. Hospitals were categorized by treatment volume into
      CSC or non-CSC volume status based on The Joint Commission's annual volume
      thresholds of at least 20 patients with subarachnoid hemorrhage and performance
      of 15 or more endovascular coiling or surgical clipping procedures for aneurysms.
      RESULTS A total of 65,824 patients underwent treatment for an unruptured cerebral
      aneurysm. There were 4818 patients (7.3%) in whom at least 1 PSI event occurred.
      The overall inpatient mortality rate was 0.7%. In patients with a PSI event, this
      rate increased to 7% compared with 0.2% in patients without a PSI event (p <
      0.0001). The overall rate of poor outcome was 3.8%. In patients with a PSI event,
      this rate increased to 23.3% compared with 2.3% in patients without a PSI event
      (p < 0.0001). There were significant differences in PSI event, poor outcome, and
      mortality rates between non-CSC and CSC volume-status hospitals (PSI event, 8.4%
      vs 7.2%; poor outcome, 5.1% vs 3.6%; and mortality, 1% vs 0.6%). In multivariate
      analysis, all patients treated at a non-CSC volume-status hospital were more
      likely to suffer a PSI event with an OR of 1.2 (1.1-1.3). In patients who
      underwent surgery, this relationship was more substantial, with an OR of 1.4 (1.2
      1.6). The relationship was not significant in the endovascularly treated
      patients. CONCLUSIONS In the treatment of unruptured cerebral aneurysms, PSI
      events occur relatively frequently and are associated with significant increases
      in morbidity and mortality. In patients treated at institutions achieving the
      volume thresholds for CSC certification, the likelihood of having a PSI event,
      and therefore the likelihood of poor outcome and mortality, was significantly
      decreased. These improvements are being driven by the improved outcomes in
      surgical patients, whereas outcomes and mortality in patients treated
      endovascularly were not sensitive to the CSC volume status of the hospital and
      showed no significant relationship with treatment volumes.

PMID- 29053071
TI  - Prevention of postoperative visual field defect after the occipital
      transtentorial approach: anatomical study.
AB  - OBJECTIVE A postoperative visual field defect resulting from damage to the
      occipital lobe during surgery is a unique complication of the occipital
      transtentorial approach. Though the association between patient position and this
      complication is well investigated, preventing the complication remains a
      challenge. To define the area of the occipital lobe in which retraction is least
      harmful, the surface anatomy of the brain, course of the optic radiations, and
      microsurgical anatomy of the occipital transtentorial approach were examined.
      METHODS Twelve formalin-fixed cadaveric adult heads were examined with the aid of
      a surgical microscope and 0 degrees  and 45 degrees  endoscopes. The optic
      radiations were examined by fiber dissection and MR tractography techniques.
      RESULTS The arterial and venous relationships of the lateral, medial, and
      inferior surfaces of the occipital lobe were defined anatomically. The full
      course of the optic radiations was displayed via both fiber dissection and MR
      tractography. Although the stems of the optic radiations as exposed by both
      techniques are similar, the terminations of the fibers are slightly different.
      The occipital transtentorial approach provides access for the removal of lesions
      involving the splenium, pineal gland, collicular plate, cerebellomesencephalic
      fissure, and anterosuperior part of the cerebellum. An angled endoscope can aid
      in exposing the superior medullary velum and superior cerebellar peduncles.
      CONCLUSIONS Anatomical findings suggest that retracting the inferior surface of
      the occipital lobe may avoid direct damage and perfusion deficiency around the
      calcarine cortex and optic radiations near their termination. An accurate
      understanding of the course of the optic radiations and vascular relationships
      around the occipital lobe and careful retraction of the inferior surface of the
      occipital lobe may reduce the incidence of postoperative visual field defect.

PMID- 29053072
TI  - Quantitative assessment of changes in hemodynamics of the internal carotid artery
      after bypass surgery for moyamoya disease.
AB  - OBJECTIVE Although intracranial vessel remodeling has been observed in moyamoya
      disease, concerns remain regarding the effect of bypass surgery on hemodynamic
      changes within the internal carotid artery (ICA). The authors aimed to quantify
      the surgical effect of bypass surgery on bilateral ICAs in moyamoya disease and
      to estimate pressure drop (PD) along the length of the ICA to predict surgical
      outcomes. METHODS Records of patients who underwent bypass surgery for treatment
      of moyamoya disease and in whom flow rates were obtained pre- and postsurgery by
      quantitative MR angiography were retrospectively reviewed. Quantitative MR
      angiography and computational fluid dynamics were applied to measure
      morphological and hemodynamic changes during pre- and postbypass procedures. The
      results for vessel diameter, volumetric flow, PD, and mean wall shear stress
      along the length of the ICA were analyzed. Subgroup analysis was performed for
      the circle of Willis (CoW) configurations. RESULTS Twenty-three patients were
      included. The PD in ICAs on the surgical side (surgical ICAs) decreased by 21.18%
      (SD +/- 30.1%) and increased by 11.75% (SD +/- 28.6%) in ICAs on the nonsurgical
      side (contralateral ICAs) (p = 0.001). When the PD in contralateral ICAs was
      compared between patients with a complete or incomplete CoW, the authors found
      that the PDI in the former group decreased by 2.45% and increased by 20.88% in
      the latter (p = 0.05). Regression tests revealed that a greater postoperative
      decrease in PD corresponded to shrinking of ICAs (R2 = 0.22, p = 0.02).
      CONCLUSIONS PD may be used as a reliable biomechanical indicator for the
      assessment of surgical treatment outcomes. The vessel remodeling characteristics
      of contralateral ICA were related to CoW configurations.

PMID- 29053073
TI  - Chronic subthreshold cortical stimulation for adult drug-resistant focal
      epilepsy: safety, feasibility, and technique.
AB  - OBJECTIVE Epilepsy surgery is effective for lesional epilepsy, but it can be
      associated with significant morbidity when seizures originate from eloquent
      cortex that is resected. Here, the objective was to describe chronic subthreshold
      cortical stimulation and evaluate its early surgical safety profile in adult
      patients with epilepsy originating from seizure foci in cortex that is not
      amenable to resection. METHODS Adult patients with focal drug-resistant epilepsy
      underwent intracranial electroencephalography monitoring for evaluation of
      resection. Those with seizure foci in eloquent cortex were not candidates for
      resection and were offered a short therapeutic trial of continuous subthreshold
      cortical stimulation via intracranial monitoring electrodes. After a successful
      trial, electrodes were explanted and permanent stimulation hardware was
      implanted. RESULTS Ten patients (6 males) who underwent chronic subthreshold
      cortical stimulation between 2014 and 2016 were included. Based on radiographic
      imaging, intracranial pathologies included cortical dysplasia (n = 3),
      encephalomalacia (n = 3), cortical tubers (n = 1), Rasmussen encephalitis (n =
      1), and linear migrational anomaly (n = 1). The duration of intracranial
      monitoring ranged from 3 to 20 days. All patients experienced an uneventful
      postoperative course and were discharged home with a median length of stay of 10
      days. No postoperative surgical complications developed (median follow-up length
      7.7 months). Seizure severity and seizure frequency improved in all patients.
      CONCLUSIONS The authors' institutional experience with this small group shows
      that chronic subthreshold cortical stimulation can be safely and effectively
      performed in appropriately selected patients without postoperative complications.
      Future investigation will provide further insight to recently published results
      regarding mechanism and efficacy of this novel and promising intervention.

PMID- 29053074
TI  - Clinical improvement associated with targeted interruption of the
      cerebellothalamic tract following MR-guided focused ultrasound for essential
      tremor.
AB  - OBJECTIVE The objective of this study was to evaluate the utility of diffusion
      tensor imaging (DTI) tractography-based targeting of the dentatorubrothalamic
      tract (DRT) for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy
      in patients with essential tremor (ET) and correlate postprocedural tract
      disruption with clinical outcomes. METHODS Four patients received preprocedural
      and immediate postprocedural DTI in addition to traditional anatomical MRI
      sequences for MRgFUS thalamotomy. Optimal ablation sites were selected based on
      the patient-specific location of the DRT as demonstrated by DTI (direct
      targeting) and correlated with traditional atlas-based measurements for thalamic
      ventral intermediate nucleus (Vim) lesioning (indirect targeting). Fiber tracts
      were displayed three-dimensionally during the procedure and used in conjunction
      with clinical signs of tremor control for fine correction of the ablation site.
      Immediately following the conclusion of the procedure, the MRgFUS head frame was
      removed and patients were placed in a 32-channel MRI head coil for follow-up DTI
      and anatomical MRI sequences. RESULTS All patients had excellent postoperative
      tremor control and successful pre- and postprocedural DTI fiber tracking of the
      corticospinal tract, medial lemniscus, and DRT. Immediate postprocedure DTI
      failed to track the DRT ipsilateral to the lesion site with a preserved
      contralateral DRT, coincident with substantial resolution of contralateral
      tremor. CONCLUSIONS DTI can reliably identify the optimal ablation target and
      demonstrates tract disruption on immediate postprocedural imaging. A clinical
      improvement of ET was observed immediately following the procedure, correlating
      with DRT disruption and suggesting that interruption of the DRT is a consequence
      of clinically successful MRgFUS thalamotomy. These findings may have utility for
      both MRgFUS procedure planning in surgically naive patients and retreatment of
      patients who have previously undergone unsuccessful thalamic Vim lesioning.

PMID- 29053075
TI  - Machine learning applied to neuroimaging for diagnosis of adult classic Chiari
      malformation: role of the basion as a key morphometric indicator.
AB  - OBJECTIVE The current diagnostic criterion for Chiari malformation Type I (CM-I),
      based on tonsillar herniation (TH), includes a diversity of patients with
      amygdalar descent that may be caused by a variety of factors. In contrast,
      patients presenting with an overcrowded posterior cranial fossa, a key
      characteristic of the disease, may remain misdiagnosed if they have little or no
      TH. The objective of the present study was to use machine-learning classification
      methods to identify morphometric measures that help discern patients with classic
      CM-I to improve diagnosis and treatment and provide insight into the etiology of
      the disease. METHODS Fifteen morphometric measurements of the posterior cranial
      fossa were performed on midsagittal T1-weighted MR images obtained in 195 adult
      patients diagnosed with CM. Seven different machine-learning classification
      methods were applied to images from 117 patients with classic CM-I and 50
      controls matched by age and sex to identify the best classifiers discriminating
      the 2 cohorts with the minimum number of parameters. These classifiers were then
      tested using independent CM cohorts representing different entities of the
      disease. RESULTS Machine learning identified combinations of 2 and 3 morphometric
      measurements that were able to discern not only classic CM-I (with more than 5 mm
      TH) but also other entities such as classic CM-I with moderate TH and CM Type 1.5
      (CM-1.5), with high accuracy (> 87%) and independent of the TH criterion. In
      contrast, lower accuracy was obtained in patients with CM Type 0. The distances
      from the lower aspect of the corpus callosum, pons, and fastigium to the foramen
      magnum and the basal and Wackenheim angles were identified as the most relevant
      morphometric traits to differentiate these patients. The stronger significance (p
      < 0.01) of the correlations with the clivus length, compared with the
      supraoccipital length, suggests that these 5 relevant traits would be affected
      more by the relative position of the basion than the opisthion. CONCLUSIONS
      Tonsillar herniation as a unique criterion is insufficient for radiographic
      diagnosis of CM-I, which can be improved by considering the basion position. The
      position of the basion was altered in different entities of CM, including classic
      CM-I, classic CM-I with moderate TH, and CM-1.5. The authors propose a predictive
      model based on 3 parameters, all related to the basion location, to discern
      classic CM-I with 90% accuracy and suggest considering the anterior alterations
      in the evaluation of surgical procedures and outcomes.

PMID- 29053076
TI  - Protective effect of biodegradable nerve conduit against peripheral nerve
      adhesion after neurolysis.
AB  - OBJECTIVE Peripheral nerve adhesion caused by extraneural and intraneural scar
      formation after neurolysis leads to nerve dysfunction. The authors previously
      developed a novel very flexible biodegradable nerve conduit composed of poly(L
      lactide) and poly(epsilon-caprolactone) for use in peripheral nerve regeneration.
      In the present study, they investigated the effect of protective nerve wrapping
      on preventing adhesion in a rat sciatic nerve adhesion model. METHODS Rat sciatic
      nerves were randomly assigned to one of the following four groups: a no-adhesion
      group, which involved neurolysis alone without an adhesion procedure; an adhesion
      group, in which the adhesion procedure was performed after neurolysis, but no
      treatment was subsequently administered; a nerve wrap group, in which the
      adhesion procedure was performed after neurolysis and protective nerve wrapping
      was then performed with the nerve conduit; and a hyaluronic acid (HA) group, in
      which the adhesion procedure was performed after neurolysis and nerve wrapping
      was then performed with a 1% sodium HA viscous solution. Six weeks
      postoperatively, the authors evaluated the extent of scar formation using
      adhesion scores and biomechanical and histological examinations and assessed
      nerve function with electrophysiological examination and gastrocnemius muscle
      weight measurement. RESULTS In the adhesion group, prominent scar tissue
      surrounded the nerve and strongly adhered to the nerve biomechanically and
      histologically. The motor nerve conduction velocity and gastrocnemius muscle
      weight were the lowest in this group. Conversely, the adhesion scores were
      significantly lower, motor nerve conduction velocity was significantly higher,
      and gastrocnemius muscle weight was significantly higher in the nerve wrap group
      than in the adhesion group. Additionally, the biomechanical breaking strength was
      significantly lower in the nerve wrap group than in the adhesion group and HA
      group. The morphological properties of axons in the nerve wrap group were
      preserved. Intraneural macrophage invasion, as assessed by the number of CD68-
      and CCR7-positive cells, was less severe in the nerve wrap group than in the
      adhesion group. CONCLUSIONS The nerve conduit prevented post-neurolysis
      peripheral nerves from developing adhesion and allowed them to maintain their
      nerve function because it effectively blocked scarring and prevented adhesion
      related damage in the peripheral nerves.

PMID- 29053077
TI  - Critical review of a scientific manuscript: a practical guide for reviewers.

PMID- 29053078
TI  - Contralateral transmaxillary corridor: an augmented endoscopic approach to the
      petrous apex.
AB  - OBJECTIVE The endoscopic endonasal approach (EEA) has been shown to be an
      effective means of accessing lesions of the petrous apex. Lesions that are
      lateral to the paraclival segment of the internal carotid artery (ICA) require
      lateralization of the paraclival segment of the ICA or a transpterygoid
      infrapetrous approach. In this study the authors studied the feasibility of
      adding a contralateral transmaxillary (CTM) corridor to provide greater access to
      the petrous apex with decreased need for manipulation of the ICA. METHODS Using
      image guidance, EEA and CTM extension were performed bilaterally on 5 cadavers.
      The anterior wall of the sphenoid sinus and rostrum were removed. The angle of
      the surgical approach from the axis of the petrous segment of the ICA was
      measured. Five illustrative clinical cases are presented. RESULTS The CTM
      corridor required a partial medial maxillectomy. When measured from the axis of
      the petrous ICA, the CTM corridor decreased the angle from 44.8 degrees  +/- 2.78
      degrees  to 20.1 degrees  +/- 4.31 degrees , a decrease of 24.7 degrees  +/- 2.58
      degrees . Drilling through the CTM corridor allowed the drill to reach lateral
      aspects of the petrous apex that would have required lateralization of the ICA or
      would not have been accessible via EEA. The CTM corridor allowed us to achieve
      gross-total resection of the petrous apex region in 5 clinical cases with
      significant paraclival extension. CONCLUSIONS The CTM corridor is a feasible
      extension to the standard EEA to the petrous apex that offers a more lateral
      trajectory with improved access. This approach may reduce the risk and morbidity
      associated with manipulation of the paraclival ICA.

PMID- 29053079
TI  - Letter to the Editor. Delayed parent vessel occlusion in Pipeline embolization.

PMID- 29053080
TI  - Aerosolizing Lipid Dispersions Enables Antibiotic Transport Across Mimics of the
      Lung Airway Surface Even in the Presence of Pre-existing Lipid Monolayers.
AB  - BACKGROUND: Secondary lung infections are the primary cause of morbidity
      associated with cystic fibrosis lung disease. Aerosolized antibiotic inhalation
      is potentially advantageous but has limited effectiveness due to altered airway
      aerodynamics and deposition patterns that limit drug access to infected regions.
      One potential strategy to better reach infected areas is to formulate aerosols
      with surfactants that induce surface tension gradients and drive postdeposition
      drug dispersal via Marangoni transport along the airway surface liquid (ASL).
      Since this relies on surfactant-induced surface tension reduction, the presence
      of endogenous lipid monolayers may hinder drug dispersal performance. METHODS:
      Tobramycin solutions were formulated with dipalmitoylphosphatidylcholine (DPPC),
      a major component of endogenous pulmonary surfactant, to drive postdeposition
      aerosol dispersal across a model ASL based on a liquid layer or "subphase" of
      aqueous porcine gastric mucin (PGM) solution with predeposited DPPC monolayers to
      mimic the endogenous surfactant. In vitro subphase samples were collected from
      regions outside the aerosol deposition zone and assayed for tobramycin
      concentration using a closed enzyme donor immunoassay. The motion of a tracking
      bead across the subphase surface and the corresponding decrease in surface
      tension on aerosol deposition were tracked both with and without a predeposited
      DPPC monolayer. The surface tension/area isotherm for DPPC on PGM solution
      subphase was measured to aid in the interpretation of the tobramycin dispersal
      behavior. RESULTS AND CONCLUSIONS: Transport of tobramycin away from the
      deposition region occurs in aerosols formulated with DPPC whether or not
      predeposited lipid is present, and tobramycin concentrations are similar in both
      cases across biologically relevant length scales (~8 cm). When DPPC is deposited
      from an aerosol, it induces ultralow surface tensions (<5 mN/m), which drive
      Marangoni flows, even in the presence of a dense background layer of DPPC.
      Therefore, aerosolized phospholipids, such as DPPC, will likely be effective
      spreading agents in the human lung.

PMID- 29053081
TI  - PCL and PCL-based materials in biomedical applications.
AB  - Biodegradable polymers have met with an increasing demand in medical usage over
      the last decades. One of such polymers is poly(epsilon-caprolactone) (PCL), which
      is a polyester that has been widely used in tissue engineering field for its
      availability, relatively inexpensive price and suitability for modification. Its
      chemical and biological properties, physicochemical state, degradability and
      mechanical strength can be adjusted, and therefore, it can be used under harsh
      mechanical, physical and chemical conditions without significant loss of its
      properties. Degradation time of PCL is quite long, thus it is used mainly in the
      replacement of hard tissues in the body where healing also takes an extended
      period of time. It is also used at load-bearing tissues of the body by enhancing
      its stiffness. However, due to its tailorability, use of PCL is not restricted to
      one type of tissue and it can be extended to engineering of soft tissues by
      decreasing its molecular weight and degradation time. This review outlines the
      basic properties of PCL, its composites, blends and copolymers. We report on
      various techniques for the production of different forms, and provide examples of
      medical applications such as tissue engineering and drug delivery systems
      covering the studies performed in the last decades.

PMID- 29053082
TI  - Letter to the Editor. Alternative C-1 screw placement technique.

PMID- 29053083
TI  - Surgical management of penetrating spinal cord injury primarily due to shrapnel
      and its effect on neurological outcome: a literature review and meta-analysis.
AB  - OBJECTIVE This study was performed to determine whether decompression of
      penetrating spinal cord injury (SCI) due to explosive shrapnel leads to greater
      neurological recovery than conservative management. METHODS In accordance with
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)
      guidelines, a comprehensive literature search using PubMed/MEDLINE, Web of
      Science, Google Scholar, and the Defense Technical Information Center public site
      was conducted on May 2, 2016. Studies that described penetrating SCI with
      shrapnel as an etiology, included surgical and/or conservative management, and
      demonstrated admission and follow-up neurological status were eligible for
      inclusion in this study. Odds ratios were calculated for the overall effect of
      surgical treatment on neurological recovery. Funnel plots were used to evaluate
      publication bias. RESULTS Five case series (Level IV evidence) met the study
      criteria, and 2 of them had estimable odds ratios for use in the Forest plot
      analysis. Among the patients from all 5 studies, 65% were injured by shrapnel,
      25% by high-velocity bullet, 8% by low-velocity bullet, and 2% by an unknown
      cause. A total of 288 patients were included in the overall odds ratio
      calculations. Patients were stratified by complete and incomplete SCI. The meta
      analysis showed no significant difference in outcomes between surgical and
      conservative management in the complete SCI cohort or the incomplete SCI cohort.
      Overall rates of improvement for complete SCI were 25% with surgery and 27% with
      conservative treatment (OR 1.07, 95% CI 0.44-2.61, p = 0.88); for incomplete SCI,
      70% with surgery and 81% with conservative treatment (OR 1.67, 95% CI 0.68-4.05,
      p = 0.26). CONCLUSIONS This study demonstrates no clear benefit to surgical
      decompression of penetrating SCI due predominantly to shrapnel. There is a
      considerable need for nonrandomized prospective cohort studies examining
      decompression and stabilization surgery for secondary and tertiary blast
      injuries.

PMID- 29053084
TI  - Intubation biomechanics: validation of a finite element model of cervical spine
      motion during endotracheal intubation in intact and injured conditions.
AB  - OBJECTIVE Because of limitations inherent to cadaver models of endotracheal
      intubation, the authors' group developed a finite element (FE) model of the human
      cervical spine and spinal cord. Their aims were to 1) compare FE model
      predictions of intervertebral motion during intubation with intervertebral motion
      measured in patients with intact cervical spines and in cadavers with spine
      injuries at C-2 and C3-4 and 2) estimate spinal cord strains during intubation
      under these conditions. METHODS The FE model was designed to replicate the
      properties of an intact (stable) spine in patients, C-2 injury (Type II odontoid
      fracture), and a severe C3-4 distractive-flexion injury from prior cadaver
      studies. The authors recorded the laryngoscope force values from 2 different
      laryngoscopes (Macintosh, high intubation force; Airtraq, low intubation force)
      used during the patient and cadaver intubation studies. FE-modeled motion was
      compared with experimentally measured motion, and corresponding cord strain
      values were calculated. RESULTS FE model predictions of intact intervertebral
      motions were comparable to motions measured in patients and in cadavers at
      occiput-C2. In intact subaxial segments, the FE model more closely predicted
      patient intervertebral motions than did cadavers. With C-2 injury, FE-predicted
      motions did not differ from cadaver measurements. With C3-4 injury, however, the
      FE model predicted greater motions than were measured in cadavers. FE model cord
      strains during intubation were greater for the Macintosh laryngoscope than the
      Airtraq laryngoscope but were comparable among the 3 conditions (intact, C-2
      injury, and C3-4 injury). CONCLUSIONS The FE model is comparable to patients and
      cadaver models in estimating occiput-C2 motion during intubation in both intact
      and injured conditions. The FE model may be superior to cadavers in predicting
      motions of subaxial segments in intact and injured conditions.

PMID- 29053086
TI  - Age, context, and spatial memory: A neuropsychological approach.
AB  - The hypothesis that a reduction in age differences in spatial location memory in
      the presence of distinctive cues reflects a decreased dependence on a
      hippocampally based memory system was tested in three experiments. In Experiments
      1 and 2 the presence of distinctive cues did not reduce age differences in
      spatial location memory nor did these cues eliminate the significant relation
      between spatial location memory and a measure of hippocampal function.
      Distinctive cues did, however, place additional demands on processing resources
      and spatial visualization abilities. In Experiment 3 the relevance of prior
      knowledge was manipulated. With irrelevant prior knowledge there was a strong
      unique association between the hippocampal measure and outcome measure. With
      relevant prior knowledge there was no such association. the implications of these
      findings for understanding the role of the hippocampus in age-related decline in
      memory for locations are discussed.

PMID- 29053085
TI  - Rifampicin Resistance and Multidrug-Resistant Tuberculosis Detection Using Xpert
      MTB/RIF in Wuhan, China: A Retrospective Study.
AB  - BACKGROUND: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA) can simultaneously
      detect the Mycobacterium tuberculosis (MTB) complex DNA and rifampicin (RFP)
      resistance and can rapidly determine RFP resistance and predict multidrug
      resistant tuberculosis (MDR-TB). In this study, we analyzed clinical examination
      results of a hospital specializing in TB treatment in Wuhan, Hubei, China, and
      examined the use of traditional culture and drug-sensitive test (DST) results as
      a gold standard to assess the diagnosis value of the Xpert MTB/RIF test in RFP
      resistance and MDR-TB. MATERIALS AND METHODS: A total of 2,910 specimens were
      received in the Mycobacteriology Laboratory, Wuhan Pulmonary Hospital, for Xpert
      MTB/RIF testing between December 2013 and December 2014. After the results were
      reviewed by exclusion criteria, 1,066 Xpert test results were eligible for our
      study. We then compared the Xpert test results with sputum acid-fast bacilli
      staining, cultures, and DST results. RESULTS: In total, Xpert correctly
      identified 96.71% (147/152) RFP-resistant TB and 98.25% (898/914) RFP-sensitive
      TB specimens. Of the 147 RFP-resistant TB specimens detected by Xpert, 122 MDR-TB
      (82.99%) were identified by traditional culture and DST techniques. CONCLUSIONS:
      Xpert can simultaneously detect MTB and RFP resistance with high sensitivity and
      specificity. Thus, Xpert testing aids in saving a considerable amount of time in
      the diagnosis and treatment of MDR-TB.

PMID- 29053087
TI  - Editorial board page for "Aging, Neuropsychology, and Cognition", Volume 4,
      Number 4.
AB  - This is a scanned image of the original Editorial Board page(s) for this issue.

PMID- 29053088
TI  - Memory improvement tapes: How effective for elderly adults?
AB  - The effectiveness of two commercially available audiocassette memory improvement
      programs was evaluated in a sample of 32 healthy, community-living elderly
      adults. Participants were given a set of either Syber Vision's Neuropsychology of
      Memory Power tapes (Bornstein, 1989) or Nightingale-Conant's Mega Memory tapes
      (Trudeau, 1992), and a portable cassette player, and instructed to complete the
      programs within 10 weeks. All participants received a comprehensive battery of
      memory tests prior to and immediately following the memory improvement programs.
      Participants completing the memory improvement programs showed no greater gains
      in memory test performance than no-treatment control participants, but did report
      greater confidence in their memory abilities. Participants completing the Mega
      Memory program thought they were less likely to develop Alzheimer's disease after
      having completed it compared with participants in the other two conditions.
      Participants reported finding both tape programs acceptable and potentially
      useful for improving memory; those who completed the Memory Power program
      reported somewhat greater satisfaction than those completing the Mega Memory
      program. the claims about rapid, dramatic memory improvement with use of these
      products were not substantiated in this group of elderly adults and appear to be
      grossly exaggerated.

PMID- 29053089
TI  - Effects of aging on voluntary and involuntary shifts of attention.
AB  - This experiment examined adult age differences in the speed and accuracy of
      voluntary and involuntary shifts of visual attention. Younger and older adults
      performed two spatial cuing tasks using central cues and abrupt onset peripheral
      cues presented at stimulus onset asynchronies (SOAs) of 100, 150, 200, 250, and
      300 ms. Analyses of the magnitudes of cuing effects revealed a similar time
      course for younger and older adults in the central cue condition, but not in the
      peripheral condition. Analyses of the Brinley plot for central cues across cue
      validity conditions indicated that as much as 93% of the variance could be
      attributed to age-related general slowing rather than to differential aging of a
      specific visual orienting mechanism.

PMID- 29053090
TI  - Unawareness of social interaction and emotional control deficits in alzheimer's
      disease.
AB  - The purpose of this study was to examine unawareness of deficit in Alzheimer's
      disease (AD) in a previously unexplored functional domain: social interaction and
      emotional control competency. Impairment of awareness was measured by calculating
      the degree to which patients and their caregivers disagreed on ratings of patient
      functioning. to assess potential underlying mechanisms or associated features of
      social/emotional unawareness, a regression equation examining disease and
      demographic correlates was created. In addition, to provide a basis of comparison
      for the social/emotional domain, unawareness of deficit was also assessed in two
      previously examined domains of functioning (i.e., cognitive and self-care
      competency). Results revealed that, as compared to caregivers, AD-diagnosed
      patients overestimated their social/emotional competency but to a lesser extent
      than they overestimated cognitive and self-care competencies. Regression analysis
      suggested that impaired awareness of social interaction and emotional control
      deficits was positively correlated with dementia severity and negatively
      correlated with education.

PMID- 29053091
TI  - Influences of clustering and switching on the verbal fluency performance of
      patients with alzheimer's disease.
AB  - Several lines of evidence suggest that in Alzheimer's disease (AD) there is a
      progressive degradation of the hierarchical organization of semantic memory. to
      evaluate this hypothesis, clustering and switching on phonemic and semantic
      fluency tasks were studied. For elderly controls, both clustering and switching
      were correlated with the numbers of correct words generated on both fluency
      tests, but the contribution of clustering was greater on the semantic task.
      Patients with AD generated fewer correct words and made fewer switches than
      controls on both fluency tests. the average size of their semantic clusters was
      smaller and the contribution of clustering to word generation was less than for
      controls. Severity of dementia was correlated with the numbers of correct words
      and switches, but not with cluster size. These results are consistent with
      various hypotheses which maintain that the structure of semantic memory in AD is
      degraded but provide no evidence that this process is progressive. Instead,
      progressive worsening of verbal fluency in AD seems to be more strongly
      associated with the deterioration of mechanisms that govern initiation of search
      for appropriate subcategories.

PMID- 29053093
TI  - ?

PMID- 29053092
TI  - Varying patterns of verbal recall, recognition, and response bias with
      progression of alzheimer's disease.
AB  - Aspects of performance on verbal list learning tasks, such as recall,
      recognition, and response bias, may vary with severity in Alzheimer's disease
      (AD). We administered a 10-item, single-category word list learning test using
      selective reminding procedures to 188 patients with probable AD and 36 healthy
      normal controls with equivalent age and education. We analyzed the total number
      of words recalled as well as discrimination and response bias indexes derived
      from signal detection theory. Recall and discrimination were impaired in patients
      with probable AD compared to controls, and recall scores were more sensitive to
      dementia severity than discrimination. While many AD patients showed a liberal
      response bias, their response bias varied considerably within patient groups and
      did not correlate with disease severity.

PMID- 29053094
TI  - ?

PMID- 29053095
TI  - [Cannabis is not for children or adolescents].
AB  - The Danish parliament has decided to establish a four-year pilot scheme for
      medical treatment with cannabis. We increasingly experience requests from parents
      for medical treatment with cannabis of children and have the impression that a
      growing number of parents treat their children with illegally acquired cannabis
      products for various conditions. We summarize the sparse evidence regarding
      effects, side effects and long-term effects of medical treatment with cannabis in
      children and adolescents. At present, cannabis should very rarely be considered
      as part of medical treatment for children and adolescents.

PMID- 29053096
TI  - [Scaphoid fracture in a seven-year-old girl].
AB  - We report a case of a seven-year-old girl, who had a scaphoid fracture, which
      occurred when she fell off her bicycle. She was examined in the emergency room. X
      ray did not show any sign of fracture of the scaphoid, but the fracture was later
      verified with a magnetic resonance imaging scan. She wore a shin cast for eight
      weeks and recovered completely. Very few cases of children aged under eight years
      and diagnosed with scaphoid fracture have been reported in the literature.
      Scaphoid fracture should be suspected and examined for in all children with
      relevant trauma and symptoms, regardless of age.

PMID- 29053097
TI  - [Amputation of the forefoot in a 14-year-old boy due to infiltrative glomus
      tumour].
AB  - Glomus tumours are rare dermal tumours, which very seldom can be seen viscerally.
      The majority is benign small tumours of the skin. Malignancy has been reported in
      very few cases worldwide. The diagnosis is made clinically supported by MRI-scans
      and biopsy of the lesion. We present a case story of a 14-year-old boy, who had
      an infiltrative glomus tumour of the foot. The tumour met the criteria for
      malignancy and was operated radically by amputation of the forefoot. The post
      operative period was uncomplicated and no metastases were observed neither
      clinically nor by PET-CT scans.

PMID- 29053098
TI  - [Radiology diagnostics and treatment of acute cholecystitis].
AB  - Acute cholecystitis (AC) is mainly caused by stones in the gall bladder. Although
      cholescintigraphy has the highest sensitivity (97%) and specificity (94%) for AC,
      ultrasound is the most commonly used technique in confirming the diagnosis.
      Laparoscopic cholecystectomy is the recom-mended treatment of choice; however, in
      high-risk patients percutaneous gall bladder drainage is an attractive alter
      native approach to avoid lesions to the common bile duct. To avoid serious
      bleeding incidences, it is imperative to pause anticoagulation therapy prior to
      gall bladder drainage.

PMID- 29053099
TI  - [Peroral cholangioscopy].
AB  - Peroral cholangioscopy has been used since the 1970'es and provides direct
      visualization of the biliary tree, possibility of electrohydraulic or laser
      lithotripsy and visually guided biopsies. This paper presents an overview of the
      existing literature focusing on the Spyglass single-operator cholangioscopy
      system. Several studies indicate that cholangioscopy can improve therapy of
      difficult accessible biliary stones and histological diagnosis in patients with
      indeterminate bile duct stenoses.

PMID- 29053100
TI  - Ten years since the last Chikungunya virus outbreak in Italy: history repeats
      itself.

PMID- 29053102
TI  - Twofold stationary states in the classical spin-Hall effect.
AB  - The stationary states occurring in spin-Hall devices are investigated within the
      framework of the phenomenological two spin-channel model. It is shown that two
      different stationary states can be defined, which depends on the redistribution
      of the electric charges between the two spin-channels during the transient time.
      A first stationary state can be reached if the charge accumulation occurs inside
      each spin channel independently, while a second stationary state is reached if
      the two spin channels are undifferentiated from the point of view of the electric
      charge accumulation. The screening equations that describe the accumulation of
      electric charges due to spin-orbit coupling are derived in both cases, and the
      two stationary states are discussed in terms of the Dyakonov-Perel transport
      equations. It is shown that the equations should be generalized to spin-dependent
      electric fields in order to take into account the first stationary state. In both
      cases, the phenomenology is compatible with experimental observations.

PMID- 29053103
TI  - Ultrasound functional imaging in an ex vivo beating porcine heart platform.
AB  - In recent years, novel ultrasound functional imaging (UFI) techniques have been
      introduced to assess cardiac function by measuring, e.g. cardiac output (CO)
      and/or myocardial strain. Verification and reproducibility assessment in a
      realistic setting remain major issues. Simulations and phantoms are often
      unrealistic, whereas in vivo measurements often lack crucial hemodynamic
      parameters or ground truth data, or suffer from the large physiological and
      clinical variation between patients when attempting clinical validation.
      Controlled validation in certain pathologies is cumbersome and often requires the
      use of lab animals. In this study, an isolated beating pig heart setup was
      adapted and used for performance assessment of UFI techniques such as volume
      assessment and ultrasound strain imaging. The potential of performing
      verification and reproducibility studies was demonstrated. For proof-of
      principle, validation of UFI in pathological hearts was examined. Ex vivo porcine
      hearts (n  =  6, slaughterhouse waste) were resuscitated and attached to a mock
      circulatory system. Radio frequency ultrasound data of the left ventricle were
      acquired in five short axis views and one long axis view. Based on these slices,
      the CO was measured, where verification was performed using flow sensor
      measurements in the aorta. Strain imaging was performed providing radial,
      circumferential and longitudinal strain to assess reproducibility and inter
      subject variability under steady conditions. Finally, strains in healthy hearts
      were compared to a heart with an implanted left ventricular assist device,
      simulating a failing, supported heart. Good agreement between ultrasound and flow
      sensor based CO measurements was found. Strains were highly reproducible
      (intraclass correlation coefficients  >0.8). Differences were found due to
      biological variation and condition of the hearts. Strain magnitude and patterns
      in the assisted heart were available for different pump action, revealing large
      changes compared to the normal condition. The setup provides a valuable
      benchmarking platform for UFI techniques. Future studies will include work on
      different pathologies and other means of measurement verification.

PMID- 29053101
TI  - Daam2 driven degradation of VHL promotes gliomagenesis.
AB  - Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous
      pathways that drive cancer, but mutations in VHL are restricted to limited
      subsets of malignancies. Here we identified a novel mechanism for VHL suppression
      in tumors that do not have inactivating mutations. Using developmental processes
      to uncover new pathways contributing to tumorigenesis, we found that Daam2
      promotes glioma formation. Protein expression screening identified an inverse
      correlation between Daam2 and VHL expression across a host of cancers, including
      glioma. These in silico insights guided corroborating functional studies, which
      revealed that Daam2 promotes tumorigenesis by suppressing VHL expression.
      Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and
      facilitates its ubiquitination and degradation. Together, these studies are the
      first to define an upstream mechanism regulating VHL suppression in cancer and
      describe the role of Daam2 in tumorigenesis.

PMID- 29053104
TI  - Theoretically exact backprojection filtration algorithm for multi-segment linear
      trajectory.
AB  - A theoretically exact backprojection filtration algorithm is proved and
      implemented for image reconstruction from a multi-segment linear trajectory
      assuming fan-beam geometry. The reconstruction formula is based on a concept of
      linear PI-line (L-PI) proposed in our previous work. The proof is completed in
      two consecutive steps. In the first step, it is proved that theoretically exact
      image reconstruction can be obtained on an arbitrary L-PI line from an infinite
      straight-line trajectory. In the second step, it is shown that accurate image
      reconstruction can be achieved from a multi-segment line trajectory by
      introducing a weight function to deal with the data redundancy. Numerical
      implementation and simulation results validate the correctness of our theoretical
      results.

PMID- 29053105
TI  - Biological and dosimetric characterisation of spatially fractionated proton
      minibeams.
AB  - The biological effectiveness of proton beams varies with depth, spot size and
      lateral distance from the beam central axis. The aim of this work is to
      incorporate proton relative biological effectiveness (RBE) and equivalent uniform
      dose (EUD) considerations into comparisons of broad beam and highly modulated
      proton minibeams. A Monte Carlo model of a small animal proton beamline is
      presented. Dose and variable RBE is calculated on a per-voxel basis for a range
      of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance
      ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal
      end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator
      designed to produce uniform dose at the depth of the BP peak, had minimal impact
      on the open beam RBE values at depth. RBE changes were observed near the surface
      when the collimator was placed flush with the irradiated object, due to a higher
      neutron contribution derived from proton interactions with the collimator. For
      proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25%
      lower than the physical mean dose. A strong dependency of the EUD with fraction
      size was observed. For 20 Gy fractions, the EUD varied widely depending on the
      radiosensitivity of the cells. For radiosensitive cells, the difference was up to
      ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley
      dose rather than the mean dose. For comparative studies of uniform dose with
      spatially fractionated proton minibeams, EUD derived from a per-voxel RWD
      distribution is recommended for biological assessments of reproductive cell
      survival and related endpoints.

PMID- 29053106
TI  - Issues in quantification of registered respiratory gated PET/CT in the lung.
AB  - PET/CT quantification of lung tissue is limited by several difficulties: the lung
      density and local volume changes during respiration, the anatomical mismatch
      between PET and CT and the relative contributions of tissue, air and blood to the
      PET signal (the tissue fraction effect). Air fraction correction (AFC) has been
      shown to improve PET image quantification in the lungs. Methods to correct for
      the movement and anatomical mismatch involve respiratory gating and image
      registration techniques. While conventional registration methods only account for
      spatial mismatch, the Jacobian determinant of the deformable registration
      transformation field can be used to estimate local volume changes and could
      therefore potentially be used to correct (i.e. Jacobian Correction, JC) the PET
      signal for changes in concentration due to local volume changes. This work aims
      to investigate the relationship between variations in the lung due to
      respiration, specifically density, tracer concentration and local volume changes.
      In particular, we study the effect of AFC and JC on PET quantitation after
      registration of respiratory gated PET/CT patient data. Six patients suffering
      from lung cancer with solitary pulmonary nodules underwent [Formula: see text]F
      FDG PET/cine-CT. The PET data were gated into six respiratory gates using
      displacement gating based on a real-time position management (RPM) signal and
      reconstructed with matched gated CT. The PET tracer concentration and tissue
      density were extracted from registered gated PET and CT images before and after
      corrections (AFC or JC) and compared to the values from the reference images.
      Before correction, we observed a linear correlation between the PET tracer
      concentration values and density. Across all gates and patients, the maximum
      relative change in PET tracer concentration before (after) AFC was found to be
      16.2% (4.1%) and the maximum relative change in tissue density and PET tracer
      concentration before (after) JC was found to be 17.1% (5.5%) and 16.2% (6.8%)
      respectively. Overall our results show that both AFC or JC largely explain the
      observed changes in PET tracer activity over the respiratory cycle. We also
      speculate that a second order effect is related to change in fluid content but
      this needs further investigation. Consequently, either AFC or JC is recommended
      when combining lung PET images from different gates to reduce noise.

PMID- 29053107
TI  - Spectral imaging using clinical megavoltage beams and a novel multi-layer imager.
AB  - We assess the feasibility of clinical megavoltage (MV) spectral imaging for
      material and bone separation with a novel multi-layer imager (MLI) prototype. The
      MLI provides higher detective quantum efficiency and lower noise than
      conventional electronic portal imagers. Simulated experiments were performed
      using a validated Monte Carlo model of the MLI to estimate energy absorption and
      energy separation between the MLI components. Material separation was evaluated
      experimentally using solid water and aluminum (Al), copper (Cu) and gold (Au) for
      2.5 MV, 6 MV and 6 MV flattening filter free (FFF) clinical photon beams. An
      anthropomorphic phantom with implanted gold fiducials was utilized to further
      demonstrate bone/gold separation. Weighted subtraction imaging was employed for
      material and bone separation. The weighting factor (w) was iteratively estimated,
      with the optimal w value determined by minimization of the relative signal
      difference ([Formula: see text]) and signal-difference-to-noise ratio (SDNR)
      between material (or bone) and the background. Energy separation between layers
      of the MLI was mainly the result of beam hardening between components with an
      average energy separation between 34 and 47 keV depending on the x-ray beam
      energy. The minimum average energy of the detected spectrum in the phosphor layer
      was 123 keV in the top layer of the MLI with the 2.5 MV beam. The w values that
      minimized [Formula: see text] and SDNR for Al, Cu and Au were 0.89, 0.76 and 0.64
      for 2.5 MV; for 6 MV FFF, w was 0.98, 0.93 and 0.77 respectively. Bone
      suppression in the anthropomorphic phantom resulted in improved visibility of the
      gold fiducials with the 2.5 MV beam. Optimization of the MLI design is required
      to achieve optimal separation at clinical MV beam energies.

PMID- 29053108
TI  - Polaron effect on the bandgap modulation in monolayer transition metal
      dichalcogenides.
AB  - We theoretically study the bandgap modulation in monolayer transition metal
      dichalcogenides (TMDs) originating from the carrier-optical phonon coupling in
      the Frohlich polaron model, in which both of the surface optical phonons modes
      induced by the polar substrate and the intrinsic longitudinal optical phonons
      modes have been taken into account. We find that the modulated magnitude of the
      bandgap is in the range of 100-500 meV by altering different polar substrates and
      tuning the internal distance between TMDs and polar substrate. The large
      tunability of the bandgap not only provides a possible explanation for the
      experimental measurements regarding the dielectric environmental sensitivity of
      the bandgap, but also holds promise for potential applications in optoelectronics
      and photovoltaics.

PMID- 29053109
TI  - Pulsed cavitational therapy using high-frequency ultrasound for the treatment of
      deep vein thrombosis in an in vitro model of human blood clot.
AB  - Post-thrombotic syndrome, a frequent complication of deep venous thrombosis, can
      be reduced with early vein recanalization. Pulsed cavitational therapy (PCT)
      using ultrasound is a recent non-invasive approach. We propose to test the
      efficacy and safety of high-frequency focused PCT for drug-free thrombolysis
      (thrombotripsy) in a realistic in vitro model of venous thrombosis. To reproduce
      venous thrombosis conditions, human whole blood was allowed to clot by stasis in
      silicone tubes (6 mm internal diameter) at a 30 cm H2O pressure, maintained
      during the whole experiment. We engineered an ultrasound device composed of dual
      2.25 MHz transducers centered around a 6 MHz imaging probe. A therapeutic focus
      was generated at a 3.2 cm depth from the probe. Thrombotripsy was performed by
      longitudinally scanning the thrombus at three different speeds: 1 mm s-1 (n  = 
      6); 2 mm s-1 (n  =  6); 3 mm s-1 (n  =  12). Restored outflow was measured every
      three passages. Filters were placed to evaluate the debris size. Twenty-four
      occlusive thrombi, of 2.5 cm mean length and 4.4 kPa mean stiffness, were
      studied. Flow restoration was systematically obtained by nine subsequent passages
      (4.5 min maximum). By varying the device's speed, we found an optimal speed of 1
      mm s-1 to be efficient for effective recanalization with 90 s (three passages).
      Within 90 s, flow restoration was of 80, 62 and 74% at respectively 1, 2 and 3 mm
      s-1. For all groups, cavitation cloud drilled a 1.7 mm mean diameter channel
      throughout the clot. Debris analysis showed 92% of debris  <10 um, with no
      fragment  >  200 um.

PMID- 29053110
TI  - A method for acquiring random range uncertainty probability distributions in
      proton therapy.
AB  - In treatment planning we depend upon accurate knowledge of geometric and range
      uncertainties. If the uncertainty model is inaccurate then the plan will produce
      under-dosing of the target and/or overdosing of OAR. We aim to provide a method
      for which centre and site-specific population range uncertainty due to inter
      fraction motion can be quantified to improve the uncertainty model in proton
      treatment planning. Daily volumetric MVCT data from previously treated
      radiotherapy patients has been used to investigate inter-fraction changes to
      water equivalent path-length (WEPL). Daily image-guidance scans were carried out
      for each patient and corrected for changes in CTV position (using rigid
      transformations). An effective depth algorithm was used to determine residual
      range changes, after corrections had been applied, throughout the treatment by
      comparing WEPL within the CTV at each fraction for several beam angles. As a
      proof of principle this method was used to quantify uncertainties for inter
      fraction range changes for a sample of head and neck patients of [Formula: see
      text] mm, [Formula: see text] mm and overall [Formula: see text] mm. For prostate
      [Formula: see text] mm, [Formula: see text] mm and overall [Formula: see text]
      mm. The choice of beam angle for head and neck did not affect the inter-fraction
      range error significantly; however this was not the same for prostate. Greater
      range changes were seen using a lateral beam compared to an anterior beam for
      prostate due to relative motion of the prostate and femoral heads. A method has
      been developed to quantify population range changes due to inter-fraction motion
      that can be adapted for the clinic. The results of this work highlight the
      importance of robust planning and analysis in proton therapy. Such information
      could be used in robust optimisation algorithms or treatment plan robustness
      analysis. Such knowledge will aid in establishing beam start conditions at
      planning and for establishing adaptive planning protocols.

PMID- 29053111
TI  - Are the triple surface plasmon resonances in Zn nanoparticles true?
AB  - It has been experimentally and numerically confirmed that zinc (Zn) nanoparticles
      (NPs) dispersed in silica exhibit two optical extinction peaks around ~250 nm
      (1st peak) and ~1050 nm (2nd peak), both of which were ascribed to surface
      plasmon resonances (SPRs) in the broad sense, i.e., the dual SPRs. Recently,
      Kuiri and Majhi (KM) observed the 3rd peak around ~900 nm by calculations, and
      proposed the triple SPRs for Zn NPs without any experimental confirmation. This
      paper claims that the 3rd peak has never been observed in any experiments nor in
      any calculations except given by KM. They justified the triple resonances from an
      approximated SPR criterion, epsilon 1Zn(omega) + 2epsilon 1SiO2 (omega) = 0,
      which is not valid for non-idealized metals like Zn, because the imaginary part
      of the dielectric function epsilon 2Zn(omega) is not negligible. Instead, a
      rigorous SPR criterion predicts the dual resonances only. From comparisons with
      ab initio band calculations, the 1st and 2nd extinction peak are ascribed to
      resonantly enhanced inter-band transitions (so-called electronic resonance) and
      intra-band transitions (SPR in the narrow sense), respectively. Since either of
      the peaks arises from the resonant enhancement due to the dielectric function,
      both the peaks are regarded as SPRs in the broad sense, i.e. the dual SPRs.

PMID- 29053112
TI  - Bone repair of critical-sized defects in Wistar rats treated with autogenic,
      allogenic or xenogenic bone grafts alone or in combination with natural latex
      fraction F1.
AB  - Bone grafts are used in the medical-surgical field for anatomical and functional
      reconstruction of lost bone areas, aiding the bone repair process by
      osteogenesis, osteinduction and osteoconduction. New materials such as F1
      (fraction 1) protein extracted from the rubber tree Hevea brasiliensis have been
      investigated and currently present important properties for tissue repair, and
      are associated with neoangiogenesis, promoting cell adhesion and extracellular
      matrix formation. The main objective of this study was to investigate the
      association of F1 protein to different bone grafts in the repair of critical bone
      defects in the calvaria of Wistar rats. A total of 112 Wistar rats were divided
      as follows: autograft (AuG), allograft (AlG), xenograft (XeG), autograft/F1 (AuG
      F1), allograft/F1 (AlG-F1), xenograft/F1 (XeG-F1), F1 (F1), control (CTL), with a
      waiting period of 4 and 6 weeks (w). The stereological AuG, AlG, AuG-F1 and AlG
      F1 results had greater bone neoformation (p < 0.05). For immunohistochemistry,
      the angiogenic and osteogenic factors were higher for AuG-F1 and AlG-F1. TRAP
      positive cells were higher in XeG-F1 and AlG (37 +/- 9.53, 13.3 +/- 4.16) (4 w)
      and XeG, AlG-F1 and XeG-F1 (20.33 +/- 7.37; 15.25 +/- 6.02, 19.33 +/- 3.21) (6
      w). For zymography, F1 showed increased gelatinolytic activity of MMP-2 and -9.
      It was concluded that the bone graft associated or not with F1 increases the
      angiogenic and osteogenic, biochemical and stereological factors.

PMID- 29053113
TI  - An Automated Critical Event Screening and Notification System to Facilitate
      Preanesthesia Record Review.
AB  - BACKGROUND: Anesthesia information management systems make prior anesthesia
      records readily available for review when patients return for a subsequent
      procedure but may create a problem of too much documentation to review in a
      limited amount of time. We implemented a screening tool to facilitate the
      identification of critical documentation for review. METHODS: An algorithm was
      developed to electronically search prior anesthesia records for predefined
      critical events and flag records containing these events. Our web-based daily
      case schedule was modified to contain a warning message for any patient on the
      schedule who has a prior record flagged by the system, in addition to a
      preexisting hyperlink to view the relevant record. A retrospective analysis was
      performed to determine the impact of the warning messages on the frequency with
      which the care team reviewed these records before providing anesthesia care.
      RESULTS: The screening algorithm flagged 13% of archived cases as critical. There
      were 3329 and 3369 cases in the 6 months before and after system implementation,
      respectively, that had prior critical records available for review at that time.
      One or more of these critical records were viewed before the subsequent case
      start in 39% vs 59% (P < .01) of cases in the pre- versus postimplementation
      periods. Subgroup analysis revealed that the increase was greatest for attending
      anesthesiologists working alone. CONCLUSIONS: We created a system to
      automatically detect critical events in prior anesthesia records for the purpose
      of forewarning the anesthesia care team when the same patient returns for another
      procedure. Inclusion of these warnings on the daily case schedule was associated
      with an increased frequency of preanesthesia review of old records.

PMID- 29053115
TI  - [Syndrome of rapid eye movement sleep behavior disorder and nocturia in
      Parkinson's disease].
AB  - AIM: Parasomnia, a syndrome of rapid eye movement sleep behavior disorder (RBD),
      is a common non-motor impairment in patients with Parkinson's disease (PD). The
      relationship between RBD with other symptoms of PD affecting night sleep, in
      particular, nocturia, is understudied. An aim of the study was to determine the
      symptoms related to night sleep disturbances in PD patients with RBD and assess
      the dynamics of these disturbances with the disease progression taking into
      account RBD onset. MATERIAL AND METHODS: One hundred and forty patients (72 male
      and 68 female) with PD without dementia (mean age 61.98+/-0.79 years, PD stage -
      2.35+/-0.05, duration 5.82+/-90.65 years) were examined. Motor disorders were
      assessed with the unified Parkinson's disease rating scale (UPDRS), sleep
      disturbances and frequent night urinations were evaluated with the Parkinson's
      Disease Sleep Scale (PDSS). The diagnosis of probable RBD was based on reports of
      patients or their relatives on the dream-related motor activity and vocalization.
      Quality-of-life was evaluated with the Parkinson's Disease Questionnaire (PDQ
      39). Patients were followed up after 2.5 years. RESULTS: Probable RBD was
      diagnosed in 46.43% of patients, including 30.77%, who developed the syndrome
      before the manifestation of motor symptoms, 16.92% patients with simultaneous
      development of RBD and motor symptoms and 52.31% with RBD development >2 years
      after motor disorders. Patients with RBD differed from those without parasomnia
      by the higher severity of nocturia. After 2.5 years of follow-up, the severity of
      disease was greater in patients with RBD assessed by UPDRS, quality-of-life
      indices, severity of nocturia and episodes of nocturia. The highest frequency of
      episodes of nocturia was noted in patients with early onset of RBD before the
      manifestation of motor symptoms. CONCLUSION: RBD in patients with PD is
      associated with the rapid progress of nocturia, higher degree of worsening of
      daily activities and deterioration of quality of life. The relationship between
      RBD and progression of nighttime urination suggests common pathophysiological
      mechanisms of their development, which include the structural changes in the
      brain stem nuclei. The diagnosis of RBD is one of the markers of spreading of
      neurodegenerative pathology into the brain stem that resulted in the unfavorable
      disease course.

PMID- 29053114
TI  - [Evolution of the schizophrenic deficit concept].
AB  - The relevance of this study is the high prevalence and clinical heterogeneity of
      deficit states in chronic schizophrenia and schizophrenia spectrum disorders. The
      study aimed at analyzing negative symptoms in schizophrenia and schizophrenia
      spectrum disorders from historical and modern perspectives. An analysis of
      available literature, along with own observations, has been performed. It was
      found that negative symptoms comprise 3 clinical types: 1) 'pseudopsychopathic'
      type (overlapping personality dimensions and premorbid/initial negative
      symptoms), 2) pseudoorganic/asthenic/pseudobradiphrenic type (pseudoorganic
      states), developing at different stages of schizophrenia), 3) 'new'-life
      pseudopsychopathic type (not associated with premorbid personality traits),
      developing at late stages in schizophrenia. The trajectory heterogeneity of
      negative symptoms in their relation to positive symptoms has been defined:
      simultaneous-continuous course (synchronous course of positive and negative
      symptoms), polar course (alternative development of predominantly positive or
      negative symptoms), simultaneous-phasic course (pseudopsychopathic negative
      symptoms, attracting depressive symptoms, or depression that exacerbates latent
      deficit). The authors discuss some aspects of psychopharmacological treatment of
      negative symptoms. Negative symptoms in schizophrenia and schizophrenia spectrum
      disorders differ clinically, have heterogeneous trajectory course, and require
      differentiated approach with regard to psychopathological qualification,
      prognosis and treatment.

PMID- 29053117
TI  - [Autoaggressive characteristics of married couples, where husbands suffer from
      alcohol dependence].
AB  - AIM: To study autoaggressive characteristics of spouses in families of men with
      alcohol dependence. MATERIAL AND METHODS: One hundred and twenty-five families,
      where a husband suffers from alcohol dependence, have been investigated. Suicidal
      and non-suicidal patterns of autoaggressive behavior as well as their predictors
      have been studied. The control group consisted of 62 families, where husbands
      were not alcohol dependent. RESULTS AND CONCLUSION: It has been found that men
      with alcohol dependence tend to realize anivital programs through suicidal
      behavior and risky-victim behavioral modes. A history of a suicidal attempt was
      revealed in 32% of alcohol dependent men, a suicide attempt over the last two
      years in 12% that was considerably higher compared to the control group. The
      percentage in their wives was 16% and 7.2%, respectively. The suicide attempts in
      wives were due to 'prosuicidal' complex of emotions with the sense of shame,
      guilt and hopelessness. Gender differences in the ways of realization of suicidal
      attempts have been found. This finding can be used in addiction treatment.

PMID- 29053116
TI  - [Abdominal pain in migraine patients].
AB  - AIM: To study the frequency of comorbid abdominal pain in migraine patients and
      the influence of that symptom on the formation of disease phenotype. MATERIAL AND
      METHODS: Clinical features of migraine were studied in 66 patients with episodic
      migraine and 40 patients with chronic migraine. Presence of pain, intensity,
      duration of seizure-associated abdominal pain and interictal abdominal pain were
      assessed. RESULTS AND CONCLUSION: The frequency of abdominal pain in the painful
      phase of migraine was >11% and did not depend on the type of migraine. Pain in
      the abdomen were reported by 88% of patients, with the increase in the frequency
      in patients with chronic migraine. The intensity and frequency of abdominal pain
      did not depend on organic pathology of the digestive system. Correlations between
      the intensity and duration of abdominal pain during the migraine attack phase
      (k=0.59), between the intensity of associated pain and maladjustment severity
      (k=0.59), and also between the abdominal pain intensity during the painful phase
      and in the interictal period were identified. Allodynia developed more frequently
      in patients with abdominal pain between migraine attacks (RF=0.005). Also
      relationships between the level of intensity of interictal abdominal pain and the
      rates of alexithymia (k=0.24), anxiety (k=0.29) and depression (k=0.25) were
      revealed. The association of abdominal pain with disease severity and allodynia
      suggests similar development of these symptoms.

PMID- 29053118
TI  - [Nooklerin (deanoli aceglumas) in the treatment of astenic and cognitive
      disorders in patients with borderline psychopatological conditions].
AB  - BACKGROUND: This work is devoted to the combined therapy of asthenic syndrome in
      psychiatric patients due to the importanmce of studies of clinical signs of
      asthenic disorders and their comorbidity with psychiatric and somatic diseases.
      AIM: To evaluate the efficacy and safety of deanoli aceglumas (nooklerin) in
      treatment of asthenic and cognitive disorders in patients with borderline
      psychopathological conditions. MATERIAL AND METHODS: Sixty patients were enrolled
      in the study (30 patients of the main group and 30 patients of the control
      group). All patients received psychopharmacological treatment. Nooklerin was
      administered as add-on in the daily dose of 1000 mg in the main group.
      Psychopathological and psychometric examinations were conducted. The duration of
      treatment with nooklerin was 30 days. RESULTS: There was a significant reduction
      of asthenic and cognitive disorders in the main group compared to the controls.
      The good tolerability of nooklerin in the absence of a negative effect on the
      main disease was shown. CONCLUSION: The possibility of using deanoli aceglumas
      (nooklerin) as a drug of choice in combined treatment of asthenic and cognitive
      disorders in patients with borderline psychopathological conditions is confirmed.

PMID- 29053119
TI  - [Peptidergic nootropic therapy in cerebral palsy associated with epilepsy].
AB  - AIM: To assess the efficacy and safety of sortexin in the treatment of children
      with cerebral palsy (CP) combined with epilepsy. MATERIAL AND METHODS: Eighty
      four patients (55 boys and 29 girls), aged from 1 to 11 years, with CP combined
      with epilepsy received cortexin together with antiepileptic drugs (AEDs).
      Cortexin was administered in doses of 5-10 mg depending on the patient's age and
      body weight intramuscularly during hospitalization. RESULTS AND CONCLUSION:
      Cortexin as add-on to AEDs reduced for more than two times the number of
      seizures, along with improvement of motor function, in 31 (36.9%) patients. The
      improvement of motor function, but without a significant decrease in epileptic
      seizures, was achieved in 15 (17.8%) of the patients. Reduction of epileptic
      seizures frequency (>2 times), but without a significant effect on motor
      function, was observed in 14 cases (16.7%). Twenty-three patients (27.4%) did not
      respond the therapy. The aggravation of epileptic seizures during cortexin
      therapy was observed in only 1 girl with West syndrome (1.2%), and this was
      significantly lower than the probability of seizures aggravation on AED.
      Polypeptide nootropic medication cortexin demonstrated efficacy and safety as
      adjunctive therapy in children with CP combined with epilepsy.

PMID- 29053120
TI  - [Results of multicenter study of efficacy and safety of divaza in the treatment
      of the asthenic and mild to moderate cognitive disorders in elderly and senile
      subjects].
AB  - AIM: To study the efficacy and safety of divasa in elderly and senile subjects
      with asthenic and mild to moderate cognitive disorders. MATERIAL AND METHODS: The
      study included 126 patients with clinically significant asthenia and mild to
      moderate cognitive disorders. Asthenia was assessed with MFI-20, cognitive
      disorders with MMSE, clock drawing test and verbal association test. All patients
      were treated with divasa in dose 2 tablets 3 times a day. RESULTS AND CONCLUSION:
      The efficacy and safety of divasa in asthenic and mild to moderate cognitive
      disorders in elderly and senile subjects were shown. There is a need for a
      multicenter placebo-controlled trial on the efficacy of divasa to treat cognitive
      and asthenic disorders in elderly patients.

PMID- 29053121
TI  - [Possibilities of cavinton therapy regimen for infusions and cavinton comforte in
      acute and early recovery periods after ischemic stroke].
AB  - AIM: To study the efficacy of a current regimen of treatment with cavinton for
      infusions and cavinton comforte in patients with ischemic stroke in acute and
      early recovery periods and to evaluate an impact of treatment on erythrocyte
      deformity using atomic power microscopy. MATERIAL AND METHODS: One hundred and
      sixty-four patients with hemispheric ischemic stroke, aged from 30 to 79 years,
      were randomized into main (n=100) and control (n=64) groups. Patients of the main
      group received complex treatment (basic therapy and cavinton R for drop infusions
      (10 intravenously during 10 days) followed by cavinton R comforte in dose 10 mg,
      1 tablet 3 times a day during 90 days). Patients of the control group received
      basic therapy only. NIHSS, the Rankin scale, the Barthel index, MMSE, MoCA, the
      Rivermead scale, Beck depression scale, HADS were used to measure the severity of
      patient's state. To study the erythrocyte membrane by estimating Young's modulus,
      dry preparations were made with the following scanning of erythrocytes using
      atomic power microscopy. RESULTS: Positive changes on all scales were observed in
      both groups. Higher scores on NIHSS, Rankin, Barthel, MoCA, MMSE, Rivermead
      mobility index were found in the main group compared to the controls. There were
      no differences in scores on the Beck depression scale and HADS. A decrease in
      Young's modulus was found in the main group while in the control group this index
      remained unchanged. CONCLUSION: More rapid and complete regression of
      neurological deficit, better recovery of self-care function, cognitive function
      and social activity, an increase in erythrocyte membrane elasticity were found in
      the main group compared to the control one. These results indicate the efficacy
      of cavinton R and cavinton R comforte in the regimen used in complex treatment in
      acute and early recovery periods after ischemic stroke.

PMID- 29053122
TI  - [Clinical and electromyography characteristics of chemotherapy-induced
      polyneuropathy].
AB  - AIM: The study aimed at determining clinical and electromyography characteristics
      and developing the methods of CIPN treatment. MATERIAL AND METHODS: A clinical
      and electromyographic examinations and treatment of 30 with CIPN symptoms
      developed after polychemotherapy were performed. The authors developed treatment
      schemes included allopathic, homeopathic drugs, hydrotherapy and
      pharmacopuncture. RESULTS AND CONCLUSION: Most of the patients were diagnosed
      with axonal polyneuropathy with affection of long nerves of the limbs, some
      patients had a combination of axonopathy with myelopathy. After treatment,
      regression of neuropathy symptoms and improvement of quality of life was noted in
      all patients.

PMID- 29053123
TI  - [Indices of the antioxidant system and dopamine in blood plasma in the dynamics
      of microwave resonance therapy in patients with alcoholism].
AB  - AIM: To study effects of microwave resonance therapy (MWRT) on the level of
      dopamine and some indices of the antioxidant system of blood plasma in patients
      with alcohol dependence. MATERIAL AND METHODS: Dopamine, reduced glutathione,
      activities of catalase and superoxidismutase (SOD) were measured in blood plasma
      of alcoholic patients (50 men) before and after therapy. Plasma of 25 physically
      and mentally healthy men matched for age was used as control. RESULTS: In
      alcoholic patients in withdrawal state, the significant increase in dopamine
      (p=0.03), activity of catalase and SOD (p<0.05) as well as a decrease in reduced
      glutathione (p<0.01) in blood plasma in comparison with controls were found. The
      level of dopamine decreased significantly as after conventional therapy, as well
      after the therapy with addition of MWRT. After MWRT, the level of glutathione in
      blood plasma increased significantly and activities of catalase and SOD decreased
      practically up to the control level while after conventional therapy (without
      MWRT), the indices of the antioxidant system did not change significantly.
      CONCLUSION: The inclusion of MWRT in complex treatment of patients with
      alcoholism contributes to the normalization of the activity of catalase and SOD
      and increases the level of reduced glutathione, but has no significant effect on
      blood plasma dopamine level.

PMID- 29053124
TI  - [The efficacy of cerebrolysin in the treatment of autism spectrum disorders].
AB  - AIM: To evaluate clinical and neurophysiological changes in children with
      different variants of autism spectrum disorders during treatment with
      cerebrolysin. MATERIAL AND METHODS: Forty-three children with autism spectrum
      disorders, aged 4-6 years, were included in the study. To assess the degree of
      autism, the quantitative scale of assessing the severity of child autism CARS
      ('Childhood Autism Rating Scale') was used. A comparative analysis of the
      clinical picture of disease and data of the electroencephalographic examination
      in endogenous and exogenous (organic) variant of autism was made. RESULTS AND
      CONCLUSION: In children with exogenous (organic) autism, the lower scores of
      autistic symptom on the CARS and a greater degree of functional immaturity of the
      cerebral cortex, according to electroencephalographic results, were found
      compared to children with endogenous autism. After treatment with cerebrolysin,
      27 children (62.8%) showed signs of improvement. An improvement was noted in 13
      children in with endogenous autism (56.5%) and in 14 children with organic autism
      (70.0%). CARS scores showed a more pronounced decrease in this indicator in a
      subgroup of children with organic autism.

PMID- 29053125
TI  - [Ultrastructural pathology of oligodendrocytes in the white matter in continuous
      paranoid schizophrenia: a role for microglia].
AB  - AIM: Previously the authors have reported the ultrastructural pathology and
      deficit of oligodendrocytes in gray and white matter of the prefrontal cortex in
      schizophrenia. The aim of the study was to determine of the effects of microglia
      on the ultrastructure of oligodendrocytes in the white matter underlying the
      prefrontal cortex in continuous schizophrenia. MATERIAL AND METHODS: Postmortem
      morphometric electron microscopic study of oligodendrocytes in close apposition
      to microglia was performed in white matter underlying the prefrontal cortex
      (BA10). Eleven cases of chronic continuous schizophrenia and 11 normal controls
      were studied. Areas of oligodendrocytes, of their nuclei and cytoplasm, volume
      density (Vv) and the number of mitochondria, vacuoles of endoplasmic reticulum
      and lipofuscin granules were estimated. Group comparison was performed using
      ANCOVA. RESULTS: The schizophrenia group differed from the control group by
      paucity of ribosomes in the cytoplasm of oligodendrocytes, a significant decrease
      in Vv and the number of mitochondria and increase in the number of lipofuscin
      granules. Significant correlations between the parameters of lipofuscin granules,
      mitochondria and vacuoles were found only in the schizophrenia group. The number
      of lipofuscin granules were correlated positively with the illness duration.
      CONCLUSION: Dystrophic alterations of oligodendrocytes attached to microglial
      cells were found in the white matter of the prefrontal cortex in chronic paranoid
      schizophrenia as compared to controls. The data obtained suggest that microglia
      might contribute to abnormalities of energy, lipid and protein metabolism of
      oligodendrocytes in schizophrenia.

PMID- 29053126
TI  - [Effect of cytokine genes and season of birth on personality].
AB  - AIM: To evaluate the interaction effects of season of birth and immune system
      genes on the personality traits 'Novelty seeking' (NS) and 'Self-directedness'
      (SD). Based on results on an influence of the immune system on the brain
      processes, the authors hypothesized that the interaction of immune system genes
      and season of birth, which is relevant for immune phenotype, can contribute to
      the development of personality traits. MATERIAL AND METHODS: NS and SD were
      measured in 336 healthy volunteers, aged from 16 to 67 years, using the
      Temperament and Character Inventory (TCI-125). IL1B C3954T, IL4 C-589T, IL13
      C1112T and TNFA G-308A polymorphisms were genotyped. RESULTS: An interaction
      effect of IL4 C-589T and season of birth on the personality traits was found
      (F2,322=6.03, pcorr=0.011, eta2=0.04). Carriers of the minor allele T, who were
      born in winter, had lower NS and higher SD. There was a nominal main effect of
      genotype on SD (F=5.44, p=0.020) as well, with higher SD scores in carriers of
      the allele T compared to the CC genotype. CONCLUSION: The results suggest that
      the etiology of personality and immune characteristics can share common genetic
      elements including IL-4.

PMID- 29053127
TI  - [Tinnitus: algorithm of diagnostics and clinical management].
AB  - Hearing of sound, or tinnitus, can be a symptom of different diseases. The
      differential diagnosis should be based on the identification of subgroups with
      confirmed causes of the disease. Subjective and objective tinnitus groups should
      be isolated. Objective tinnitus can be vascular or muscular. In making a
      diagnosis of tinnitus, it is important to know its characteristics, laterality,
      circumstances of onset, duration, comorbidity with other symptoms: headache,
      hearing decline, dizziness, depression, etc. Urgent diagnostic and treatment
      measures are needed after the identification of 'red flags': acute pulsatile
      tinnitus, in particular after the brain injury, combination of tinnitus with
      acute hearing loss and depression.

PMID- 29053128
TI  - [Traumatic brain injury: neurologic and psychiatric aspects].
AB  - Traumatic brain injury is among the leading social-medical problems that causes
      preventable deaths, health deterioration and disability in young individuals. It
      is manifested by neurologic and psychiatric disorders, firstly by neurocognitive
      impairment. Therapeutic interventions in traumatic brain injury include
      correction of cerebral disorders in the acute phase of trauma, treatment of
      neurocognitive impairment and symptomatic treatment of mental disorders. The
      efficacy of treatment of neurocognitive deficits associated with brain injury is
      still unsatisfactory, which determines the need to find new medicines and
      therapeutic approaches.

PMID- 29053129
TI  - [Medication overuse headache].
AB  - Rebound headache (RH) is a chronic daily headache which occurs when analgesics,
      triptans, ergotamines are taken frequently (more than 15 days/month for more than
      3 months) to relieve headaches. The prevalence of RH is 1 to 4% in the general
      population. RH commonly occurs in patients with migraine and tension-type
      headache. The deficit of central sensitization and psychological factors play an
      important role in initiating and maintaining of RH. Treatment of noofen for 2
      months is effective in 75% of patients with RH.

PMID- 29053130
TI  - [Multimodal serotonergic antidepressants].
AB  - Based on the original literature, the author for the first time describes a
      history of selective serotonergic antidepressants simultaneously inhibiting the
      serotonin reuptake and directly interacting with serotonin receptors. A history
      of creation and introduction of their main representatives is presented. A
      history of investigation of their neurochemical activity is analyzed in details.
      The history of the evolution of their classifications is systemized. The data
      presented suggest the rationale for unifying all selective serotonergic
      antidepressants, simultaneously inhibiting the serotonin reuptake and directly
      interacting with serotonin receptors (trazodone, etoperidone, nefazodone,
      vilazodone, vortioxetine), in one group of 'multimodal serotonergic
      antidepressants'. The expediency to include this group in the modern
      neurochemical classification of nootropic drugs is substantiated.

PMID- 29053131
TI  - [Perspectives of the diagnosis of Alzheimer's disease using optic coherent
      tomography].
AB  - There is a constant search for new possibilities of the diagnosis of
      neurodegenerative diseases that cause dementia. The problem is important because
      of the growing prevalence of dementia, 60-80% of which are caused by Alzheimer's
      disease (AD). Over the last years, changes in the retina are thought to be a
      marker neurodegeneration. Assessment of these changes is performed using a method
      of optical coherent tomography (OCT) that allows taking cross-sectional imaging
      of a tissue. OCT is considered a potential biomarker of the early stage of AD.
      Identification of the relationship of the changes in retina and the optic nerve
      with cognitive impairment open new possibilities for the diagnosis of AD.

PMID- 29053132
TI  - [Neurotropic effect of B vitamins in the complex treatment of pain syndrome].
AB  - Combined vitamin preparations in therapeutic doses are used, along with simple
      analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), muscle and epidural
      blockade, for the relief of acute pain. It is recommended to use the B vitamin
      preparation neuromultivit. The tablet form of this preparation contains vitamin
      thiamine hydrochloride (100 mg), pyridoxine hydrochloride (200 mg),
      cyanocobalamin (0.2 mg), and injectable form includes thiamine hydrochloride
      (100mg), pyridoxine hydrochloride (100 mg), cyanocobalamin (1 mg). The efficacy
      of neuromultivit in a two stage scheme (intramuscular injections of 2 ml daily
      for 5-10 days with further injections 2-3 times a week for 2-3 weeks at the
      initial stage and 1 tablet 3 times a day for 4 weeks at the second stage) was
      shown.

PMID- 29053133
TI  - [Ophthalmic disorders as a manifestation of Parkinson's disease].
AB  - Parkinson's disease is a severe neurodegenerative disease accompanied with the
      degeneration of dopaminergic neurons in the central and peripheral nervous
      system. The diagnosis of Parkinson's disease can still be made only on the stage
      of irreversible and nearly total degeneration of the nigrostriatum dopaminergic
      system and exhaustion of brain compensatory mechanisms that explains the low
      efficacy of therapy. Ophthalmic pathology is one of the nonmotor symptoms of
      Parkinson's disease. This can be explained firstly by the fact that eye is a
      'peripheral part of brain' and secondly by the involvement of dopaminergic
      neurons (dopamine-producing cells) that are subject to the selective degeneration
      during Parkinson's disease in the regulation of visual function in the eye and
      brain. Dopaminergic neurons and dopamine receptors are present in all structures
      of the eye. Parkinson's disease cause abnormalities not only in the retina but in
      the whole optic tract and can be considered as peripheral manifestations of the
      disease that precede the well-known motor dysfunctions. This review describes
      ophthalmological symptoms of Parkinson's disease, possible pathophysiological
      mechanisms of their development, optical disorders in experimental models of
      Parkinson's disease and also the perspectives of experimental and clinical
      studies of visual disorders for the development of preclinical diagnosis of
      Parkinson's disease.

PMID- 29053134
TI  - [Conversion ratio between different botulinum neuroprotein product in
      neurological practice].
AB  - Despite nearly 30 years of experience in the application of botulinum toxin type
      A (BTA) in clinical practice, many fundamental questions of therapy remain valid.
      There are 5 botulinum toxin type A used for neurological indications in the
      Russian Federation in 2017. They contain different number of active neuroprotein
      (150 kDa) in a therapeutic dose of the drug that may have a potential impact on
      the efficacy and duration of action. The current SmPC of each BTA stated that the
      unit of activity is unique and can not be compared with any other BTA. In
      scientific publications one can find many details concerning the equivalence
      doses of onabotulinumtoxin A (botox) and abobotulinumtoxin A (dysport) and the
      ratio of units varies from 1:1 to 1:11. However, according to clinical
      guidelines, systematic reviews and high quality research evidence of recent
      years, the ratio of units of abobotulinumtoxin A (dysport) and onabotulinumtoxin
      A (botox) is 3(2,5):1. Use of a fixed ratio of units is possible only when
      switching from one drug to another or in case of limiting access to specific
      drug. Botulinum toxin type A is the first line of therapy in the treatment of
      several neurological diseases. The most commonly used drugs of botulinum toxin
      type A (botox, dysport, xeomin) have a significant evidence base that confirms
      their efficacy and optimal safety profile. The main difference between botulinum
      toxin type A is their potential activity of action, i.e., activity units and
      total therapeutic dose.

PMID- 29053135
TI  - [Nonspecific low-back pain: approaches to diagnosis and treatment].
AB  - This review considers the problem of pain chronification process based on the
      biopsychosocial model. Treatment of nonspecific low-back pain is specifically
      highlighted. Algorithms for the management of such patients are described. The
      efficacy and safety of nimesulide is discussed.

PMID- 29053136
TI  - [Lacosamide (vimpat). Prospects for clinical application].
AB  - This article presents the review of the most significant studies of the efficacy
      and tolerability of lacosamide (LCM) in treatment of patients with focal
      epilepsy. The review includes the results of the main studies which preceded the
      official approval of LCM use in mono- and polytherapy. Results on the efficacy of
      LCM in long-term use and treatment retention in clinical practice, most effective
      LCM combinations, tolerability, an influence on cognitive and mental functions,
      advantages in treatment of elderly patients are presented. Characteristics of LCM
      in comparison with other sodium channel-blocking antiepileptic drugs and
      selection priorities are shown. The authors assess perspectives of further use of
      LCM in clinical practice.

PMID- 29053137
TI  - [Report on the 15th Weekend school for neurologists of St. Petersburg and the
      North-West Federal Region].

PMID- 29053138
TI  - miR-31a-5p promotes postnatal cardiomyocyte proliferation by targeting RhoBTB1.
AB  - A limited number of microRNAs (miRNAs, miRs) have been reported to control
      postnatal cardiomyocyte proliferation, but their strong regulatory effects
      suggest a possible therapeutic approach to stimulate regenerative capacity in the
      diseased myocardium. This study aimed to investigate the miRNAs responsible for
      postnatal cardiomyocyte proliferation and their downstream targets. Here, we
      compared miRNA profiles in cardiomyocytes between postnatal day 0 (P0) and day 10
      (P10) using miRNA arrays, and found that 21 miRNAs were upregulated at P10,
      whereas 11 were downregulated. Among them, miR-31a-5p was identified as being
      able to promote cardiomyocyte proliferation as determined by proliferating cell
      nuclear antigen (PCNA) expression, double immunofluorescent labeling for alpha
      actinin and 5-ethynyl-2-deoxyuridine (EdU) or Ki-67, and cell number counting,
      whereas miR-31a-5p inhibition could reduce their levels. RhoBTB1 was identified
      as a target gene of miR-31a-5p, mediating the regulatory effect of miR-31a-5p in
      cardiomyocyte proliferation. Importantly, neonatal rats injected with a miR-31a
      5p antagomir at day 0 for three consecutive days exhibited reduced expression of
      markers of cardiomyocyte proliferation including PCNA expression and double
      immunofluorescent labeling for alpha-actinin and EdU, Ki-67 or phospho-histone
      H3. In conclusion, miR-31a-5p controls postnatal cardiomyocyte proliferation by
      targeting RhoBTB1, and increasing miR-31a-5p level might be a novel therapeutic
      strategy for enhancing cardiac reparative processes.

PMID- 29053139
TI  - Chronic fluoxetine upregulates activity, protein and mRNA levels of cytosolic
      phospholipase A2 in rat frontal cortex.
AB  - This corrects the article DOI: 10.1038/sj.tpj.6500391.

PMID- 29053140
TI  - Measurement of BH3-only protein tolerance.
AB  - The BCL2 family of proteins regulates cellular life and death decisions. Among
      BCL2 family members, BH3-only proteins have critical roles by neutralizing
      antiapoptotic family members, as well as directly activating BAX and BAK. Despite
      widespread occurrence of BH3-only protein upregulation in response to various
      stresses, this process is rarely quantified. Moreover, it is unclear whether all
      BH3-only proteins are equipotent at inducing cell death. Here we show that BH3
      only proteins increase as much as 15- to 20-fold after various treatments and
      define a parameter, termed BH3-only tolerance, which measures how many copies of
      a particular BH3-only protein can be expressed before the majority of cells in a
      population undergo apoptosis. We not only assess the relative contributions of
      anti- and proapoptotic BCL2 family members to BH3-only tolerance, but also
      illustrate how the study of this parameter can be used to understand cellular
      sensitivity to anticancer drugs and new combinations. These observations provide
      a new quantitative framework for assessing apoptotic susceptibility under various
      conditions.

PMID- 29053141
TI  - Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation,
      reduces adiposity and improves insulin sensitivity in mice.
AB  - BCL-2 proteins are known to engage each other to determine the fate of a cell
      after a death stimulus. However, their evolutionary conservation and the many
      other reported binding partners suggest an additional function not directly
      linked to apoptosis regulation. To identify such a function, we studied mice
      lacking the BH3-only protein BIM. BIM-/- cells had a higher mitochondrial oxygen
      consumption rate that was associated with higher mitochondrial complex IV
      activity. The consequences of increased oxygen consumption in BIM-/- mice were
      significantly lower body weights, reduced adiposity and lower hepatic lipid
      content. Consistent with reduced adiposity, BIM-/- mice had lower fasting blood
      glucose, improved insulin sensitivity and hepatic insulin signalling. Lipid
      oxidation was increased in BIM-/- mice, suggesting a mechanism for their
      metabolic phenotype. Our data suggest a role for BIM in regulating mitochondrial
      bioenergetics and metabolism and support the idea that regulation of metabolism
      and cell death are connected.

PMID- 29053142
TI  - Resolution of inflammation and sepsis survival are improved by dietary Omega-3
      fatty acids.
AB  - Critical conditions such as sepsis following infection or traumatic injury
      disturb the complex state of homeostasis that may lead to uncontrolled
      inflammation resulting in organ failure, shock and death. They are associated
      with endogenous mediators that control the onset of acute inflammatory response,
      but the central problem remains the complete resolution of inflammation. Omega-3
      enriched lipid emulsions (Omega-3+ LEs) were used in experimental studies and
      clinical trials to establish homeostasis, yet with little understanding about
      their role on the resolution of inflammation and tissue regeneration. Here, we
      demonstrate that Omega-3 lipid emulsions (LEs) orchestrate inflammation
      resolution/regeneration mechanism during sterile peritonitis and murine
      polymicrobial sepsis. Omega-3+ LEs recessed neutrophil infiltration, reduced pro
      inflammatory mediators, reduced the classical monocyte and enhanced the non
      classical monocytes/macrophages recruitment and finally increased the
      efferocytosis in sepsis. The actions of Omega-3+ LE were 5-lipoxygenase (5-LOX)
      and 12/15-lipoxygenase (12/15-LOX) dependent. Omega-3+ LEs shortened the
      resolution interval by 56%, stimulated the endogenous biosynthesis of resolution
      mediators lipoxin A4, protectin DX and maresin 1 and contributed to tissue
      regeneration. Omega-3+ LEs protected against hypothermia and weight loss and
      enhanced survival in murine polymicrobial sepsis. We highlighted a role of Omega
      3+ LEs in regulating key mechanisms within the resolution terrain during murine
      sepsis. This might form the basis for a rational design of sepsis specific
      clinical nutrition.

PMID- 29053144
TI  - Uncultivated microbes-in need of their own nomenclature?

PMID- 29053143
TI  - MOMP, cell suicide as a BCL-2 family business.
AB  - Apoptosis shapes development and differentiation, has a key role in tissue
      homeostasis, and is deregulated in cancer. In most cases, successful apoptosis is
      triggered by mitochondrial outer membrane permeabilization (MOMP), which defines
      the mitochondrial or intrinsic pathway and ultimately leads to caspase activation
      and protein substrate cleavage. The mitochondrial apoptotic pathway centered on
      MOMP is controlled by an intricate network of events that determine the balance
      of the cell fate choice between survival and death. Here we will review how MOMP
      proceeds and how the main effectors cytochrome c, a heme protein that has a
      crucial role in respiration, and second mitochondria-derived activator of caspase
      (SMAC), as well as other intermembrane space proteins, orchestrate caspase
      activation. Moreover, we discuss recent insights on the interplay of the upstream
      coordinators and initiators of MOMP, the BCL-2 family. This review highlights how
      our increasing knowledge on the regulation of critical checkpoints of apoptosis
      integrates with understanding of cancer development and has begun to translate
      into therapeutic clinical benefit.

PMID- 29053145
TI  - Geometagenomics illuminates the impact of agriculture on the distribution and
      prevalence of plant viruses at the ecosystem scale.
AB  - Disease emergence events regularly result from human activities such as
      agriculture, which frequently brings large populations of genetically uniform
      hosts into contact with potential pathogens. Although viruses cause nearly 50% of
      emerging plant diseases, there is little systematic information about virus
      distribution across agro-ecological interfaces and large gaps in understanding of
      virus diversity in nature. Here we applied a novel landscape-scale
      geometagenomics approach to examine relationships between agricultural land use
      and distributions of plant-associated viruses in two Mediterranean-climate
      biodiversity hotspots (Western Cape region of South Africa and Rhone river delta
      region of France). In total, we analysed 1725 geo-referenced plant samples
      collected over two years from 4.5 * 4.5 km2 grids spanning farmlands and adjacent
      uncultivated vegetation. We found substantial virus prevalence (25.8-35.7%) in
      all ecosystems, but prevalence and identified family-level virus diversity were
      greatest in cultivated areas, with some virus families displaying strong
      agricultural associations. Our survey revealed 94 previously unknown virus
      species, primarily from uncultivated plants. This is the first effort to
      systematically evaluate plant-associated viromes across broad agro-ecological
      interfaces. Our findings indicate that agriculture substantially influences plant
      virus distributions and highlight the extent of current ignorance about the
      diversity and roles of viruses in nature.

PMID- 29053147
TI  - Dispersal timing determines the importance of priority effects in bacterial
      communities.
AB  - The order and timing of species arrival during community assembly can have long
      term effects on community structure due to priority effects. The importance of
      such processes in complex bacterial communities where dispersal involves mixing
      of entire communities is currently not known. Here we used a transplant
      experiment with two bacterioplankton communities of different origin (freshwater
      and brackish). Sterile medium of each origin was initially inoculated with a
      bacterial community of different ('alien') origin, followed by dispersal of the
      respective 'home' community at different time points after initial inoculation.
      We found that the later the dispersal with the 'home' community occurred the
      smaller the effect on the final community composition. This suggests that
      priority effects by the initially inoculated community reduce the establishment
      success of taxa from the later arriving community and that this effect depends on
      dispersal timing.

PMID- 29053146
TI  - The plant circadian clock influences rhizosphere community structure and
      function.
AB  - Plants alter chemical and physical properties of soil, and thereby influence
      rhizosphere microbial community structure. The structure of microbial communities
      may in turn affect plant performance. Yet, outside of simple systems with
      pairwise interacting partners, the plant genetic pathways that influence
      microbial community structure remain largely unknown, as are the performance
      feedbacks of microbial communities selected by the host plant genotype. We
      investigated the role of the plant circadian clock in shaping rhizosphere
      community structure and function. We performed 16S ribosomal RNA gene sequencing
      to characterize rhizosphere bacterial communities of Arabidopsis thaliana between
      day and night time points, and tested for differences in community structure
      between wild-type (Ws) vs clock mutant (toc1-21, ztl-30) genotypes. We then
      characterized microbial community function, by growing wild-type plants in soils
      with an overstory history of Ws, toc1-21 or ztl-30 and measuring plant
      performance. We observed that rhizosphere community structure varied between day
      and night time points, and clock misfunction significantly altered rhizosphere
      communities. Finally, wild-type plants germinated earlier and were larger when
      inoculated with soils having an overstory history of wild-type in comparison with
      clock mutant genotypes. Our findings suggest the circadian clock of the plant
      host influences rhizosphere community structure and function.

PMID- 29053149
TI  - Recent expansion of heat-activated retrotransposons in the coral symbiont
      Symbiodinium microadriaticum.
AB  - Rising sea surface temperature is the main cause of global coral reef decline.
      Abnormally high temperatures trigger the breakdown of the symbiotic association
      between corals and their photosynthetic symbionts in the genus Symbiodinium.
      Higher genetic variation resulting from shorter generation times has previously
      been proposed to provide increased adaptability to Symbiodinium compared to the
      host. Retrotransposition is a significant source of genetic variation in
      eukaryotes and some transposable elements are specifically expressed under
      adverse environmental conditions. We present transcriptomic and phylogenetic
      evidence for the existence of heat stress-activated Ty1-copia-type LTR
      retrotransposons in the coral symbiont Symbiodinium microadriaticum. Genome-wide
      analyses of emergence patterns of these elements further indicate recent
      expansion events in the genome of S. microadriaticum. Our findings suggest that
      acute temperature increases can activate specific retrotransposons in the
      Symbiodinium genome with potential impacts on the rate of retrotransposition and
      the generation of genetic variation under heat stress.

PMID- 29053148
TI  - Stress response of a marine ammonia-oxidizing archaeon informs physiological
      status of environmental populations.
AB  - High representation by ammonia-oxidizing archaea (AOA) in marine systems is
      consistent with their high affinity for ammonia, efficient carbon fixation, and
      copper (Cu)-centric respiratory system. However, little is known about their
      response to nutrient stress. We therefore used global transcriptional and
      proteomic analyses to characterize the response of a model AOA, Nitrosopumilus
      maritimus SCM1, to ammonia starvation, Cu limitation and Cu excess. Most
      predicted protein-coding genes were transcribed in exponentially growing cells,
      and of ~74% detected in the proteome, ~6% were modified by N-terminal
      acetylation. The general response to ammonia starvation and Cu stress was
      downregulation of genes for energy generation and biosynthesis. Cells rapidly
      depleted transcripts for the A and B subunits of ammonia monooxygenase (AMO) in
      response to ammonia starvation, yet retained relatively high levels of
      transcripts for the C subunit. Thus, similar to ammonia-oxidizing bacteria,
      selective retention of amoC transcripts during starvation appears important for
      subsequent recovery, and also suggests that AMO subunit transcript ratios could
      be used to assess the physiological status of marine populations. Unexpectedly,
      cobalamin biosynthesis was upregulated in response to both ammonia starvation and
      Cu stress, indicating the importance of this cofactor in retaining functional
      integrity during times of stress.

PMID- 29053150
TI  - Dispersal alters bacterial diversity and composition in a natural community.
AB  - Dispersal is central to the evolution and maintenance of microbial diversity.
      Quantifying microbial dispersal and its role in shaping communities remains a
      challenge, however. Here, we manipulated a bacterial community's dispersal rate
      in a grassland ecosystem and test whether this altered diversity and composition.
      We constructed bags of two nylon mesh sizes that allowed more or less bacterial
      movement and filled them with an edible or inedible substrate, irradiated plant
      litter or nylon sheets. We measured changes in bacterial abundance (using flow
      cytometry) and composition (using 16S amplicon sequencing) in the bags weekly
      over 5 months. The dispersal treatment altered bacterial colonization rates and
      led to differences in the abundance, richness, evenness and composition of
      communities. Overall, the study demonstrates that dispersal influences the
      assembly of this natural bacterial community.

PMID- 29053151
TI  - Highly structured prokaryote communities exist within the skeleton of coral
      colonies.
AB  - Physiological performance, disease and bleaching prevalence are often patchy
      within individual coral colonies. These responses are largely influenced by coral
      associated microbes, but how the coral microbiome changes over small spatial
      scales has never been quantified before. We performed a high-resolution
      quantification of the spatial scale of microbial species turnover (beta
      diversity) within skeletons of boulder-forming Porites corals. We found very
      strong prokaryotic species turnover across spatial scales ranging from 4 mm to 2
      m within individual colonies, possibly resulting from dispersal limitation and
      microbial interactions. The microalgal community was more homogeneously
      distributed, which is likely due to these photosymbionts actively boring through
      limestone. Our findings highlight unprecedented levels of intra-colony
      heterogeneity in the skeletal microbiome, which has implications for the
      experimental design of coral microbiome studies and for our understanding of
      coral resilience.

PMID- 29053153
TI  - Nutrition: Start your day with a high-energy breakfast.

PMID- 29053154
TI  - Basic research: Inhibition of Hippo pathway signalling reverses systolic heart
      failure.

PMID- 29053155
TI  - Prevention: Non-recreational physical activity reduces CVD risk.

PMID- 29053152
TI  - Heart in space: effect of the extraterrestrial environment on the cardiovascular
      system.
AB  - National space agencies and private corporations aim at an extended presence of
      humans in space in the medium to long term. Together with currently suboptimal
      technology, microgravity and cosmic rays raise health concerns about deep-space
      exploration missions. Both of these physical factors affect the cardiovascular
      system, whose gravity-dependence is pronounced. Heart and vascular function are,
      therefore, susceptible to substantial changes in weightlessness. The altered
      cardiovascular function in space causes physiological problems in the postflight
      period. A compromised cardiovascular system can be excessively vulnerable to
      space radiation, synergistically resulting in increased damage. The space
      radiation dose is significantly lower than in patients undergoing radiotherapy,
      in whom cardiac damage is well-documented following cancer therapy in the
      thoracic region. Nevertheless, epidemiological findings suggest an increased risk
      of late cardiovascular disease even with low doses of radiation. Moreover, the
      peculiar biological effectiveness of heavy ions in cosmic rays might increase
      this risk substantially. However, whether radiation-induced cardiovascular
      effects have a threshold at low doses is still unclear. The main countermeasures
      to mitigate the effect of the space environment on cardiac function are physical
      exercise, antioxidants, nutraceuticals, and radiation shielding.

PMID- 29053156
TI  - Atherosclerosis: Mitochondrial fission is crucial for efferocytosis.

PMID- 29053159
TI  - Proximity hybridization triggered rolling-circle amplification for sensitive
      electrochemical homogeneous immunoassay.
AB  - A new homogeneous electrochemical immunoassay strategy was developed for
      ultrasensitive detection of carcinoembryonic antigen (CEA) based on target
      induced proximity hybridization coupled with rolling circle amplification (RCA).
      The immobilization-free detection of CEA was realized by the use of an uncharged
      peptide nucleic acid (PNA) probe labeled with ferrocene (Fc) as the electroactive
      indicator on a negatively charged indium tin oxide (ITO) electrode. In the
      presence of a target protein and two DNA-labeled antibodies, the proximate
      complex formed in homogeneous solution could unfold the molecular beacon, and a
      part of the unfolded molecular beacon as a primer hybridized with the RCA
      template to initiate the RCA process. Subsequently, the detection probe modified
      Fc (Fc-PNAs) hybridized with the long amplified DNA products. The consumption of
      freely diffusible Fc-PNAs (neutrally charged) resulted in a significant reduction
      of the Fc signal due to the fact that long amplified DNA/Fc-PNA products were
      electrostatically repelled from the ITO electrode surface. The reduction of the
      electrochemical signal (signal-off) could indirectly provide the CEA
      concentration. Under the optimal conditions, CEA detection was implemented in a
      wide range from 1 pg mL-1 to 10 ng mL-1, with a low detection limit of 0.49 pg mL
      1. The proposed strategy exhibited advantages of good selectivity, high
      sensitivity, acceptable accuracy, and favorable versatility of analytes.
      Moreover, the practical application value of the system was confirmed by the
      assay of CEA in human serums with satisfactory results.

PMID- 29053160
TI  - Highly efficient Cs-based perovskite light-emitting diodes enabled by energy
      funnelling.
AB  - The incorporation of phenylethylammonium bromide (PEABr) into a fully inorganic
      CsPbBr3 perovskite framework led to the formation of mixed-dimensional
      perovskites, which enhanced the photoluminescence due to efficient energy
      funnelling and morphological improvements. With a PEABr : CsPbBr3 ratio of 0.8 :
      1, PeLEDs with a current efficiency of 6.16 cd A-1 and an EQE value of 1.97% have
      been achieved.

PMID- 29053158
TI  - Prevalence of myeloma precursor state monoclonal gammopathy of undetermined
      significance in 12372 individuals 10-49 years old: a population-based study from
      the National Health and Nutrition Examination Survey.
AB  - We studied the prevalence of monoclonal gammopathy of undetermined significance
      (MGUS) in younger individuals, age 10-49 years, using samples from the National
      Health and Nutritional Examination Survey (NHANES) III. NHANES prevalence rates
      were standardized to the 2000 US total population. Among 12 372 individuals (4073
      blacks, 4146 Mexican-Americans, 3595 whites, and 558 others), MGUS was identified
      in 63 persons (0.34%, 95% CI 0.23-0.50). The prevalence of MGUS was significantly
      higher in blacks (0.88%, 95% CI 0.62-1.26) compared with whites (0.22%, 95% CI
      0.11-0.45), P=0.001. The prevalence of MGUS in Mexican-Americans was at an
      intermediate level (0.41%, 95% CI 0.23-0.73). The disparity in prevalence of MGUS
      between blacks and whites was most striking in the 40-49 age-group; 3.26% (95% CI
      2.04-5.18) versus 0.53% (95% CI 0.20-1.37), P=0.0013. There was a trend to
      earlier age of onset of MGUS in blacks compared with whites. MGUS was seen in
      only two persons in the 10-19 age-group (both Mexican-American), and in three
      persons in the 20-29-year age-group (all of whom were black). In persons less
      than 50 years of age, MGUS is significantly more prevalent, with up to 10 years
      earlier age of onset, in blacks compared with whites.

PMID- 29053161
TI  - Voltammetric and spectroscopic study of ferrocene and hexacyanoferrate and the
      suitability of their redox couples as internal standards in ionic liquids.
AB  - Ionic liquids and deep eutectic solvents have great potential in metallurgical
      applications as specialised solvents. In order to design ionometallurgical
      electrowinning and electrorefining processes, it is essential to characterise the
      electrochemical behaviour of metal complexes and compare potentials between
      relevant solvents. For such investigations, a universal reference redox couple
      would be desirable. In this study we investigate the speciation and
      electrochemical behaviour of ferrocenium/ferrocene and hexacyanoferrate(iii/ii)
      as possible reference couples for 15 different ionic media on platinum (Pt),
      glassy carbon (GC) and gold (Au) working electrodes. Amongst other parameters,
      formal electrode potentials, charge transfer coefficients, and rate constants
      were calculated. It was found that neither ferrocene nor hexacyanoferrate are
      universally suitable as redox standards in the liquids investigated.
      Nevertheless, hexacyanoferrate exhibits clear advantages in most of the strongly
      coordinating ionic liquids studied here.

PMID- 29053157
TI  - Current applications of multiparameter flow cytometry in plasma cell disorders.
AB  - Multiparameter flow cytometry (MFC) has become standard in the management of
      patients with plasma cell (PC) dyscrasias, and could be considered mandatory in
      specific areas of routine clinical practice. It plays a significant role during
      the differential diagnostic work-up because of its fast and conclusive readout of
      PC clonality, and simultaneously provides prognostic information in most
      monoclonal gammopathies. Recent advances in the treatment and outcomes of
      multiple myeloma led to the implementation of new response criteria, including
      minimal residual disease (MRD) status as one of the most relevant clinical
      endpoints with the potential to act as surrogate for survival. Recent technical
      progress led to the development of next-generation flow (NGF) cytometry that
      represents a validated, highly sensitive, cost-effective and widely available
      technique for standardized MRD evaluation, which also could be used for the
      detection of circulating tumor cells. Here we review current applications of MFC
      and NGF in most PC disorders including the less frequent solitary plasmocytoma,
      light-chain amyloidosis or Waldenstrom macroglobulinemia.

PMID- 29053162
TI  - The role of association of ions in ionic liquid/molecular solvent mixtures on
      metal extraction.
AB  - Several mixtures of butyl acetate (BA) and an ionic liquid (1-methyl-3
      octylpyrrolidinium bis(trifluoromethylsulfonyl)imide, [C1C8Pyrro][NTf2], 1-octyl
      pyridinium bis(trifluoromethylsulfonyl)imide, [C8Pyr][NTf2], 1-butyl-3-methyl
      imidazolium bis(trifluoromethylsulfonyl)imide, [C1C4Im][NTf2] or 1-octyl-3-methyl
      imidazolium bis(trifluoromethylsulfonyl)imide, [C1C8Im][NTf2]) have been
      characterized by measuring density, viscosity and conductivity, from pure BA to
      pure ILs at 298.15 K. The ionicity of these mixtures has been determined on the
      basis of electrical conductivity and NMR spectroscopy. IR spectra of these
      mixtures were used to examine the interactions between ions. In parallel, Pt(iv)
      was extracted from the acidic aqueous phase towards mixtures of BA and
      [C1C8Im][NTf2] over the entire composition range. A drastic modification in the
      distribution coefficient of Pt(iv) was observed at ca xAB = 0.8. A drop was also
      observed in the ionicity of the extracting phase (IL + BA) at a similar
      composition. The variation of the distribution coefficient is ascribed to changes
      in the interactions in the mixtures, which in turn could induce changes in the
      extraction mechanism.

PMID- 29053163
TI  - Superstructures with diverse morphologies and highly ordered fullerene C60 arrays
      from 1 : 1 and 2 : 1 adamantane-C60 hybrid molecules.
AB  - Superstructures from fullerene C60-containing compounds, especially those
      tethered to rigid functional groups with defined shapes, remain largely
      unexplored. Being the smallest diamondoid, adamantane (Ad) can be viewed as a
      promising building block for the construction of well-defined superstructures.
      Here, we report the syntheses of 1 : 1 (4a) and 2 : 1 (4b) Ad-C60 hybrid
      molecules, which were then used to construct superstructures in binary solvent
      mixtures via a modified liquid/liquid interfacial precipitation (LLIP) method
      using CHCl3 as a good solvent. Typically in the combination of DMSO/CHCl3 with a
      final concentration (cf) of 1.0 mmol L-1, 4a successively forms spheres, plates,
      nanoflowers and plicated particles with increasing content of DMSO while 4b forms
      cuboid blocks and microparticles with hierarchically organized surfaces. Changing
      from DMSO to other poor solvents including acetone, MeOH and EtOAc leads to
      variations of the morphology of the superstructures for both 4a and 4b. At the
      nanometer length scale, 4a and 4b adopt different organizations within the
      superstructures. While 4a tends to self-organize into lamellae with highly
      ordered C60 layers, the hexagonal phase is dominant in the superstructures formed
      by 4b. Wettability tests indicate that films formed by the superstructures of 4a
      and 4b show anti-wetting properties. Besides the solvent effect, the morphology
      of the superstructures can be also tuned by concentration. For example, when cf
      is lowered to 0.5 mmol L-1, a new form of superstructure, i.e., fibers, was
      detected for 4a. Our results also indicate that besides the solvent-induced
      aggregate transition, gravity-induced sedimentation and subsequent structure
      ripening can have a significant influence on the final morphology of the
      superstructures and the aggregate transition pathways.

PMID- 29053164
TI  - NARRMDA: negative-aware and rating-based recommendation algorithm for miRNA
      disease association prediction.
AB  - An increasing amount of evidence indicates that microRNAs (miRNAs) are closely
      related to many important biological processes and play a significant role in
      various human diseases. More and more researchers have begun to seek effective
      methods to predict potential miRNA-disease associations. However, reliable
      computational methods to predict potential disease-related miRNAs are lacking. In
      this study, we developed a new miRNA-disease association prediction model called
      Negative-Aware and rating-based Recommendation algorithm for miRNA-Disease
      Association prediction (NARRMDA) based on the known miRNA-disease associations in
      the HMDD database, miRNA functional similarity, disease semantic similarity and
      Gaussian interaction profile kernel similarity. NARRMDA combined a rating-based
      recommendation algorithm and a negative-aware algorithm to score and rank miRNAs
      without known associations with investigated diseases. Furthermore, we used leave
      one-out cross validation to evaluate the accuracy of NARRMDA and compared NARRMDA
      with four previous classical prediction models (RLSMDA, HDMP, RWRMDA and MCMDA).
      As it turned out, NARRMDA and the other four prediction models achieved AUCs of
      0.8053, 0.6953, 0.7702, 0.7891 and 0.7718, respectively, which proved that
      NARRMDA has superior performance of prediction accuracy. Furthermore, we verified
      the prediction results associated with colon neoplasms, esophageal neoplasms,
      lymphoma and breast neoplasms by two different validation schemas. In these case
      studies, 92%, 84%, 92%, and 100% of the top 50 potential miRNAs for these four
      diseases were confirmed by experimental discoveries, respectively. These results
      further show that NARRMDA has reliable performance of prediction ability.

PMID- 29053165
TI  - Multi-exciton emission from solitary dopant states of carbon nanotubes.
AB  - By separating the photons from slow and fast decays of single and multi-exciton
      states in a time gated 2nd order photon correlation experiment, we show that
      solitary oxygen dopant states of single-walled carbon nanotubes (SWCNTs) allow
      emission of photon pairs with efficiencies as high as 44% of single exciton
      emission. Our pump dependent time resolved photoluminescence (PL) studies further
      reveal diffusion-limited exciton-exciton annihilation as the key process that
      limits the emission of multi-excitons at high pump fluences. We further postulate
      that creation of additional permanent exciton quenching sites occurring under
      intense laser irradiation leads to permanent PL quenching. With this work, we
      bring out multi-excitonic processes of solitary dopant states as a new area to be
      explored for potential applications in lasing and entangled photon generation.

PMID- 29053166
TI  - Humidity-responsive actuators from integrating liquid crystal networks in an
      orienting scaffold.
AB  - Developing shape-shifting materials requires combining the flexibility needed by
      shape-shifting properties, with the toughness that is demanded to maintain their
      mechanical performance. Typically, in liquid crystal networks, the amplitude of
      the shape transformation can be hindered by large cross-linking densities. Here,
      we argue that a promising strategy to address this limitation consists in
      integrating liquid crystal networks into an anisotropic and porous material that
      acts as an orienting scaffold. This strategy shows similarities with the
      principles of stimuli-responsive deformation in plants, where inflexible elements
      with specific orientations are integrated into a stimuli-responsive matrix. By
      aligning liquid crystals in a porous polypropylene orienting scaffold, we
      demonstrate liquid crystal networks that respond to humidity with a shape change,
      yet they display high elastic modulus and toughness. Various chiral shapes can be
      generated in single and double layers of these films, and the complexity of their
      actuation modes is enhanced, including twisting, curling or winding. We
      anticipate that these hybrid composites and the strategy they embody can find
      application to other stimuli-responsive anisotropic soft materials.

PMID- 29053167
TI  - Particle size effect of BaTiO3 nanofillers on the energy storage performance of
      polymer nanocomposites.
AB  - Polymer nanocomposites are a promising substitute for energy-storage dielectric
      materials in pulsed power systems. A barium titanate/polyvinylidenefluoride
      (BT/PVDF) nanocomposite is one of the most widely studied composite systems due
      to its comprehensive excellent dielectric properties. As the dielectric response
      of nanocomposites depends strongly on the size of the fillers, in this study,
      BT/PVDF nanocomposites with 92.3 nm, 17.8 nm and 5.9 nm BT particle fillers are
      fabricated to reveal the particle size effect of the fillers on the energy
      storage performance of the polymer nanocomposites. Owing to the small particle
      size and good dispersibility of the nanofillers, the nanocomposites with smaller
      BT particles show more uniform and denser microstructures. Moreover, with the
      increase of the filler fraction, the dielectric results indicate a breakdown
      strength enhancement in the nanocomposites with sub-20 nm BT fillers, which is
      quite different from the nanocomposites with normal fillers, and therefore leads
      to superior energy storage performance. This study provides experimental evidence
      for the application of ultrafine nanofillers in the nanocomposite for future
      energy storage systems.

PMID- 29053168
TI  - FL-926-16, a novel bioavailable carnosinase-resistant carnosine derivative,
      prevents onset and stops progression of diabetic nephropathy in db/db mice.
AB  - BACKGROUND AND PURPOSE: The advanced glycation end products (AGEs) participate in
      the pathogenesis of diabetic nephropathy (DN) by promoting renal inflammation and
      injury. L-carnosine acts as a quencher of the AGE precursors reactive carbonyl
      species (RCS), but is rapidly inactivated by carnosinase. In this study, we
      evaluated the effect of FL-926-16, a carnosinase-resistant and bioavailable
      carnosine derivative, on the onset and progression of DN in db/db mice.
      EXPERIMENTAL APPROACH: Adult male db/db mice and coeval db/m controls were left
      untreated or treated with FL-926-16 (30 mg.kg-1 body weight) from weeks 6 to 20
      (prevention protocol) or from weeks 20 to 34 (regression protocol). KEY RESULTS:
      In the prevention protocol, FL-926-16 significantly attenuated increases in
      creatinine (-80%), albuminuria (-77%), proteinuria (-75%), mean glomerular area (
      34%), fractional (-40%) and mean (-42%) mesangial area in db/db mice. This
      protective effect was associated with a reduction in glomerular matrix protein
      expression and cell apoptosis, circulating and tissue oxidative and carbonyl
      stress, and renal inflammatory markers, including the NLRP3 inflammasome. In the
      regression protocol, the progression of DN was completely blocked, although not
      reversed, by FL-926-16. In cultured mesangial cells, FL-926-16 prevented NLRP3
      expression induced by RCS but not by the AGE Nepsilon -carboxymethyllysine.
      CONCLUSION AND IMPLICATIONS: FL-926-16 is effective at preventing the onset of DN
      and halting its progression in db/db mice by quenching RCS, thereby reducing the
      accumulation of their protein adducts and the consequent inflammatory response.
      In a future perspective, this novel compound may represent a promising AGE
      reducing approach for DN therapy.

PMID- 29053169
TI  - Whole body physiologically based modelling of beta-blockers in the rat: events in
      tissues and plasma following an i.v. bolus dose.
AB  - BACKGROUND AND PURPOSE: Whole body physiologically based pharmacokinetic (PBPK)
      models have been increasingly applied in drug development to describe kinetic
      events of therapeutic agents in animals and humans. The advantage of such
      modelling is the ability to incorporate vast amounts of physiological
      information, such as organ blood flow and volume, to ensure that the model is as
      close to reality as possible. EXPERIMENTAL APPROACH: Previous PBPK model
      development of enantiomers of a series of seven racemic beta-blockers, namely,
      acebutolol, betaxolol, bisoprolol, metoprolol, oxprenolol, pindolol and
      propranolol, together with S-timolol in rat was based on tissue and blood
      concentration data at steady state. Compounds were administered in several
      cassettes with the composition mix and blood and tissue sampling times determined
      using a D-optimal design. KEY RESULTS: Closed-loop PBPK models were developed
      initially based on the application of open loop forcing function models to
      individual tissues and compounds. For the majority of compounds and tissues,
      distribution kinetics was adequately characterized by perfusion rate-limited
      models. For some compounds in the testes and gut, a permeability rate-limited
      distribution model was required to best fit the data. Parameter estimates of the
      tissue-to-blood partition coefficient through fitting of individual enantiomers
      and of racemic pair were generally in agreement and also concur with those from
      previous steady-state experiments. CONCLUSIONS AND IMPLICATIONS: PBPK modelling
      is a very powerful tool to aid drug discovery and development of therapeutic
      agents in animals and humans. However, careful consideration of the assumptions
      made during the modelling exercise is essential.

PMID- 29053170
TI  - Radiation therapy utilization in Medicare beneficiaries with early-stage breast
      cancer.
AB  - BACKGROUND: There is increasing evidence that radiation therapy (RT) can be
      omitted for select older patients who are compliant with hormonal blockade, but
      there is no recent claim-based analysis for determining patterns of care and
      guiding possible treatment recommendations. METHODS: Medicare beneficiaries who
      were 65 years old or older and were diagnosed with breast cancer at 1 of 12
      cancer centers affiliated with an academic center in the southeastern United
      States were analyzed. Stage 0 or I patients treated with lumpectomy from 2012 to
      2014 were identified. Patient, treatment, and center characteristics were
      analyzed for the utilization of RT. RESULTS: Among 800 women treated with
      lumpectomy, 64% received adjuvant radiation. The median age was 74 years. The
      omission of RT was more likely in older patients, stage 0 patients, and patients
      with more comorbidities (P < .01). Hormonal blockade was used in 41% of the
      patients who did not receive RT. The utilization of hormonal blockade with the
      omission of RT was more likely in patients with fewer comorbidities (P < .01).
      CONCLUSIONS: In an older cohort of patients who otherwise would have qualified
      for the omission of radiation, two-thirds were treated with radiation. Future
      guideline recommendations should address omission in the context of hormonal
      blockade compliance because only 41% of the patients used hormonal blockade when
      radiation was not delivered. Cancer 2018;124:475-81. (c) 2017 American Cancer
      Society.

PMID- 29053171
TI  - High Surface Area, Thermally Stable, Hydrophobic, Microporous, Rigid Gels
      Generated at Ambient from MeSi(OEt)3 /(EtO)3 SiCH2 CH2 Si(OEt)3 Mixtures by F- 
      Catalyzed Hydrolysis.
AB  - High surface area materials are of considerable interest for gas storage/capture,
      molecular sieving, catalyst supports, as well as for slow-release drug-delivery
      systems. We report here a very simple and fast route to very high surface area,
      mechanically robust, hydrophobic polymer gels prepared by fluoride-catalyzed
      hydrolysis of mixtures of MeSi(OEt)3 and bis-triethoxysilylethane (BTSE) at room
      temperature. These materials offer specific surface areas up to 1300 m2  g-1 ,
      peak pore sizes of 0.8 nm and thermal stabilities above 200  degrees C. The
      gelation times and surface areas can be controlled by adjusting the solvent
      volume (dichloromethane), percent fluoride (as nBu4 NF or TBAF) and the BTSE
      contents. Polymers with other corners and linkers were also explored. These
      materials will further expand the materials databank for use in vacuum insulation
      panels and as thermally stable release and capture media.

PMID- 29053172
TI  - Reply to ABCG2 overexpression and deoxyadenosine analogue activity in acute
      myeloid leukemia.

PMID- 29053173
TI  - The Williams' legacy: A critical reappraisal of his nine predictions about the
      evolution of senescence.
AB  - Williams' evolutionary theory of senescence based on antagonistic pleiotropy has
      become a landmark in evolutionary biology, and more recently in biogerontology
      and evolutionary medicine. In his original article, Williams launched a set of
      nine "testable deductions" from his theory. Although some of these predictions
      have been repeatedly discussed, most have been overlooked and no systematic
      evaluation of the whole set of Williams' original predictions has been performed.
      For the sixtieth anniversary of the publication of the Williams' article, we
      provide an updated evaluation of all these predictions. We present the pros and
      cons of each prediction based on recent accumulation of both theoretical and
      empirical studies performed in the laboratory and in the wild. From our
      viewpoint, six predictions are mostly supported by our current knowledge at least
      under some conditions (although Williams' theory cannot thoroughly explain why
      for some of them). Three predictions, all involving the timing of senescence, are
      not supported. Our critical review of Williams' predictions highlights the
      importance of William's contribution and clearly demonstrates that, 60 years
      after its publication, his article does not show any sign of senescence.

PMID- 29053174
TI  - Identification of Thiols in Yellow Onion (Allium cepa L.) Using Solvent Vented
      Large Volume Injection GC-MS.
AB  - Thiols are often highly odor active molecules and as such can significantly
      contribute to aroma while being present at extremely low concentrations. This
      paper details the identification of thiols in yellow onion juice by solvent
      extraction followed by thiol enrichment using a mercuric agarose gel column. Due
      to the inherent thermal instability and low concentrations of thiols in onion,
      chromatographic analysis utilized larger volume solvent elimination injections.
      New sulfur compounds in onion included 1,1-propanedithiol, bis-(1-sulfanylpropyl)
      sulfide, 1-methylsulfanyl-1-propanethiol, 1-propylsulfanyl-1-propanethiol, and 1
      allylsulfanyl-1-propanethiol. A discussion on the potential route of formation
      for each compound is included along with the orthonasal and retronasal
      evaluations of the synthesized molecules. This work investigated and identified 5
      newly identified compounds present in onions that can impart onion character at
      low concentrations levels.

PMID- 29053176
TI  - The Development of Regional Dialect Locality Judgments and Language Attitudes
      Across the Life Span.
AB  - The development of language attitudes and perception of talker regional
      background was investigated across the life span (N = 240, age range = 4-75
      years). Participants rated 12 talkers on dimensions of geographic locality,
      status, and solidarity. Children could classify some dialects by locality by age
      6-7 years and showed adult-like patterns by age 8 years. Children showed adult
      like status ratings for some dialects by age 4-5 years but were not fully adult
      like until age 12 years. Solidarity ratings were more variable and did not
      exhibit a clear developmental trajectory, although some adult-like patterns were
      in place by age 6-7 years. Locality ratings were a significant but modest
      predictor of attitude ratings, suggesting that geographic knowledge is one
      contributor to language attitudes throughout development.

PMID- 29053175
TI  - Distinct pattern of TP53 mutations in human immunodeficiency virus-related head
      and neck squamous cell carcinoma.
AB  - BACKGROUND: Human immunodeficiency virus-infected individuals (HIVIIs) have a
      higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical
      and histopathological differences have been observed in their tumors in
      comparison with those of HNSCC patients without a human immunodeficiency virus
      (HIV) infection. The reasons for these differences are not clear, and molecular
      differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This
      study compared the mutational patterns of HIV-related HNSCC and non-HIV-related
      HNSCC. METHODS: The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non
      HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes
      frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA
      A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63)
      were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA
      sequencing data were analyzed with Ion Reporter software. The human
      papillomavirus (HPV) status of the tumor samples was assessed with in situ
      hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and
      p16 immunostaining. Mutation calls were compared among the studied groups.
      RESULTS: HIV-related HNSCC revealed a distinct pattern of mutations in comparison
      with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in
      HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide
      changes for all mutated genes but especially for TP53. CONCLUSIONS: HNSCC in
      HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53
      gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV
      virus on the pathogenesis of these tumors should not be ruled out. Cancer
      2018;124:84-94. (c) 2017 American Cancer Society.

PMID- 29053177
TI  - Early effect of Medicare Shared Savings Program accountable care organization
      participation on prostate cancer care.
AB  - BACKGROUND: Accountable care organizations (ACOs) can improve prostate cancer
      care by decreasing treatment variations (ie, avoidance of treatment in low-value
      settings). Herein, the authors performed a study to understand the effect of
      Medicare Shared Savings Program ACOs on prostate cancer care. METHODS: Using a
      20% Medicare sample, the authors identified men with newly diagnosed prostate
      cancer from 2010 through 2013. Rates of treatment, potential overtreatment (ie,
      treatment in men with a >=75% chance of 10-year mortality from competing risks),
      and Medicare payments were measured using regression models. The impact of ACO
      participation was assessed using difference-in-differences analyses. RESULTS:
      Before implementation of ACOs, the treatment rate was 71.8% (95% confidence
      interval [95% CI], 70.2%-73.3%) for ACO-aligned beneficiaries and 72.3% (95% CI,
      71.7%-73.0% [P = .51]) for non-ACO-aligned beneficiaries. After implementation,
      this rate declined to 68.4% (95% CI, 66.1%-70.7% [P = .017]) for ACO-aligned
      beneficiaries and 69.3% (95% CI, 68.5%-70.1% [P<.001]) for non-ACO-aligned
      beneficiaries. There was no differential effect noted for ACO participation. The
      rate of potential overtreatment decreased from 48.2% (95% CI, 43.1%-53.3%) to
      40.2% (95% CI, 32.4%-48.0% [P = .087]) for ACO-aligned beneficiaries and
      increased from 44.3% (95% CI, 42.1%-46.5%) to 47.0% (95% CI, 44.5%-49.5% [P =
      .11]) for non-ACO-aligned beneficiaries. These changes resulted in a significant
      relative decrease in overtreatment of 17% for ACO-aligned beneficiaries
      (difference-in-differences, 10.8%; P = .031). Payments were not found to be
      differentially affected by ACO alignment. CONCLUSIONS: The treatment of prostate
      cancer and annual payments decreased significantly between 2010 and 2013, but ACO
      participation did not appear to impact these trends. Among men least likely to
      benefit, Medicare Shared Savings Program ACO alignment was associated with a
      significant decline in prostate cancer treatment. Cancer 2018;124:563-70. (c)
      2017 American Cancer Society.

PMID- 29053178
TI  - Utility of genetics for risk stratification in pediatric hypertrophic
      cardiomyopathy.
AB  - Children with hypertrophic cardiomyopathy (HCM) experience sudden cardiac death
      (SCD) and other life-threatening events. We assessed if affected gene and variant
      burden predict outcomes. Patients <18 years old with primary HCM with a
      pathogenic variant or variant of uncertain significance in cardiomyopathy genes
      were included. Association of gene and variant number and type with freedom from
      major adverse cardiac events (MACE), that is, ICD insertion, myectomy, aborted
      SCD, transplantation or death, was assessed by Cox regression. A total of 98 of
      155 gene-tested patients carried a non-benign variant. The primary affected gene
      was MYH7 in 35% (MYH7+) and MYBPC3 in 49% (MYBPC3+). MYH7+ patients had earlier
      disease onset and higher risk of MACE (hazard ratio 2.7, 95% CI 1.3-5.7). Risk of
      MACE was also higher in patients with multiple variants (n = 16) (HR 2.5, CI: 1.1
      5.9) compared to a propensity score-matched single variant subset, after
      adjustment for primary gene, and in patients with de novo (n = 18) vs inherited
      variants (HR 5.7, CI: 2.6-12.7). Affected gene (eg, MYH7), higher variant burden
      and de novo variant status are independently associated with earlier onset and
      higher frequency of adverse outcomes in pediatric HCM, highlighting the
      importance of genetic risk stratification in HCM.

PMID- 29053179
TI  - Providing Family Planning Services at Primary Care Organizations after the
      Exclusion of Planned Parenthood from Publicly Funded Programs in Texas: Early
      Qualitative Evidence.
AB  - OBJECTIVE: To explore organizations' experiences providing family planning during
      the first year of an expanded primary care program in Texas. DATA SOURCES:
      Between November 2014 and February 2015, in-depth interviews were conducted with
      program administrators at 30 organizations: 7 women's health organizations, 13
      established primary care contractors (e.g., community health centers, public
      health departments), and 10 new primary care contractors. STUDY DESIGN:
      Interviews addressed organizational capacities to expand family planning and
      integrate services with primary care. DATA EXTRACTION: Interview transcripts were
      analyzed using a theme-based approach. Themes were compared across the three
      types of organizations. PRINCIPAL FINDINGS: Established and new primary care
      contractors identified several challenges expanding family planning services,
      which were uncommon among women's health organizations. Clinicians often lacked
      training to provide intrauterine devices and contraceptive implants.
      Organizations often recruited existing clients into family planning services,
      rather than expanding their patient base, and new contractors found family
      planning difficult to integrate because of clients' other health needs. Primary
      care contractors frequently described contraceptive provision protocols that were
      not evidence-based. CONCLUSIONS: Many primary care organizations in Texas
      initially lacked the capacity to provide evidence-based family planning services
      that women's health organizations already provided.

PMID- 29053180
TI  - Infant Visual Attention and Stimulus Repetition Effects on Object Recognition.
AB  - This study examined behavioral, heart rate (HR), and event-related potential
      (ERP) correlates of attention and recognition memory for 4.5-, 6-, and 7.5-month
      old infants (N = 45) during stimulus encoding. Attention was utilized as an
      independent variable using HR measures. The Nc ERP component associated with
      attention and the late slow wave (LSW) associated with recognition memory were
      analyzed. The 7.5-month-olds demonstrated a significant reduction in Nc amplitude
      with stimulus repetition. This reduction in Nc was not found for younger infants.
      Additionally, infants only demonstrated differential LSW amplitude based on
      stimulus type on attentive trials as defined by HR changes. These findings
      indicate that from 4.5 to 7.5 months, infants' attentional engagement is
      influenced by an increasingly broader range of stimulus characteristics.

PMID- 29053181
TI  - Chiral Catenanes and Rotaxanes: Fundamentals and Emerging Applications.
AB  - Molecular chirality provides a key challenge in host-guest recognition and other
      related chemical applications such as asymmetric catalysis. For a molecule to act
      as an efficient enantioselective receptor, it requires multi-point interactions
      between host and chiral guest, which may be achieved by an appropriate chiral 3D
      scaffold. As a consequence of their interlocked structure, catenanes and
      rotaxanes may present such a 3D scaffold, and can be chiral by inclusion of a
      classical chiral element and/or as a consequence of the mechanical bond. This
      Minireview presents illustrative examples of chiral [2]catenanes and
      [2]rotaxanes, and discusses where these molecules have been used in chemical
      applications such as chiral host-guest recognition and asymmetric catalysis.

PMID- 29053182
TI  - Halide Abstraction Competes with Oxidative Addition in the Reactions of Aryl
      Halides with [Ni(PMen Ph(3-n) )4 ].
AB  - Density functional theory (DFT) calculations have been used to study the
      oxidative addition of aryl halides to complexes of the type [Ni(PMen Ph(3-n) )4
      ], revealing the crucial role of an open-shell singlet transition state for
      halide abstraction. The formation of NiI versus NiII has been rationalised
      through the study of three different pathways: (i) halide abstraction by [Ni(PMen
      Ph(3-n) )3 ], via an open-shell singlet transition state; (ii) SN 2-type
      oxidative addition to [Ni(PMen Ph(3-n) )3 ], followed by phosphine dissociation;
      and (iii) oxidative addition to [Ni(PMen Ph(3-n) )2 ]. For the overall reaction
      between [Ni(PMe3 )4 ], PhCl, and PhI, a microkinetic model was used to show that
      our results are consistent with the experimentally observed ratios of NiI and
      NiII when the PEt3 complex is used. Importantly, [Ni(PMen Ph(3-n) )2 ] complexes
      often have little, if any, role in oxidative addition reactions because they are
      relatively high in energy. The behaviour of [Ni(PR3 )4 ] complexes in catalysis
      is therefore likely to differ considerably from those based on diphosphine
      ligands in which two coordinate Ni0 complexes are the key species undergoing
      oxidative addition.

PMID- 29053183
TI  - Impact of Recent Medicaid Expansions on Office-Based Primary Care and Specialty
      Care among the Newly Eligible.
AB  - OBJECTIVE: To quantify the effect of Medicaid expansions on office-based care
      among the newly eligible. DATA SOURCE: 2008-2014 Medical Expenditure Panel
      Survey. STUDY DESIGN: The main sample is adults age 26-64 with incomes <=138% of
      poverty who were not eligible for Medicaid prior to the Affordable Care Act. For
      this population, difference-in-differences linear probability models compare
      utilization between expansion and nonexpansion states and between 2008-2013 and
      2014. EXTRACTION METHODS: Medicaid eligibility is simulated using data on family
      relationships, state of residence, and income. PRINCIPAL FINDINGS: Relative to
      comparable adults in nonexpansion states, newly eligible adults in expansion
      states were 9.1 percentage points more likely to have any office-based primary
      care physician visit in 2014, a 21.4% increase from 2013 (p-value = .004); 6.9
      percentage points more likely to have a specialist visit, a 25.2% increase from
      2013 (p-value = .036); and 5.1 percentage points more likely to have a visit with
      a nurse practitioner, nurse, or physician assistant, a 34.5% increase from 2013
      (p-value = .016). CONCLUSIONS: State Medicaid expansions in 2014 were associated
      with greater likelihoods of visits with a variety of office-based providers. The
      estimated effects are larger among newly eligible compared with previous
      estimates on broader populations of low-income adults.

PMID- 29053184
TI  - The tumor genome in human immunodeficiency virus-related head and neck cancer:
      Exploitable targets?

PMID- 29053186
TI  - ABCG2 overexpression and deoxyadenosine analogue activity in acute myeloid
      leukemia.

PMID- 29053185
TI  - Expression of the DNA repair gene MLH1 correlates with survival in patients who
      have resected pancreatic cancer and have received adjuvant chemoradiation: NRG
      Oncology RTOG Study 9704.
AB  - BACKGROUND: The majority of patients with pancreatic cancer who undergo curative
      resection experience rapid disease recurrence. In previous small studies, high
      expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in
      pancreatic cancers was associated with better outcomes. The objective of this
      study was to validate the association between MLH1 expression and survival in
      patients who underwent resection of pancreatic cancer and received adjuvant
      chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation
      Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov
      identifier NCT00003216), which compared 2 adjuvant protocols in patients with
      pancreatic cancer who underwent resection. Tissue microarrays were prepared from
      formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was
      quantified using fluorescence immunohistochemistry and automated quantitative
      analysis, and expression was dichotomized above and below the median value.
      RESULTS: Immunohistochemical staining was successfully performed on 117 patients
      for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the
      participants who had tissue samples available were similar to those of the trial
      population as a whole. At the time of analysis, 84% of participants had died,
      with a median survival of 17 months. Elevated MLH1 expression levels in tumor
      nuclei were significantly correlated with longer disease-free and overall
      survival in each arm individually and in both arms combined. Two-year overall
      survival was 16% in patients who had low MLH1 expression levels and 53% in those
      who had high MLH1 expression levels (P < .0001 for both arms combined). This
      association remained true on a multivariate analysis that allowed for lymph node
      status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001).
      CONCLUSIONS: In the current sample, MLH1 expression was correlated with long-term
      survival. Further studies should assess whether MLH1 expression predicts which
      patients with localized pancreatic cancer may benefit most from aggressive,
      multimodality treatment. Cancer 2018;124:491-8. (c) 2017 American Cancer Society.

PMID- 29053187
TI  - XIST promotes gastric cancer (GC) progression through TGF-beta1 via targeting miR
      185.
AB  - LncRNAs and microRNAs can play significant roles in various cancers, including
      gastric cancer (GC). In our study, we investigated the role of lncRNA XIST in GC.
      We observed that XIST was increased in MGC803 and BGC823 cells compared to human
      normal gastric epithelial GES-1 cells. It was also shown that miR-185 was
      decreased in GC cell lines. Silencing XIST can inhibit the growth of GC cells and
      bioinformatics analysis was performed to confirm the correlation between XIST and
      miR-185. Interestingly, a negative correlation was indicated between XIST and miR
      185 in GC cells. In addition, TGF-beta1 was predicted as a target gene of miR
      185. miR-185 can modulate TGF-beta1 expression negatively in vitro. Moreover, we
      found that sh-XIST inhibited GC development via decreasing TGF-beta1 by
      upregulating miR-185 in vitro. Therefore, we speculated that XIST can act as a
      competing endogenous lncRNA (ceRNA) to regulate TGF-beta1 by sponging miR-185 in
      GC. Taken these together, it was indicated that XIST/miR-185/TGF-beta1 axis
      participated in the development of GC. XIST could act as a potential prognostic
      biomarker in GC development.

PMID- 29053188
TI  - Trends in Risk of Pregnancy Loss Among US Women, 1990-2011.
AB  - BACKGROUND: Pregnancy loss can have physical and psychological consequences for
      women and their families. Though a previous study described an increase in the
      risk of self-reported pregnancy loss from 1970 to 2000, more recent examinations
      from population-based data of US women are lacking. METHODS: We used data from
      the 1995, 2002, 2006-2010, 2011-2015 National Survey of Family Growth on self
      reported pregnancy loss (miscarriage, stillbirth, ectopic pregnancy) among US
      women (15-44 years) who reported at least one pregnancy conceived during 1990
      2011 that did not result in induced termination (n = 20 012 women; n = 42 526
      pregnancies). Trends in the risk of self-reported pregnancy loss and early
      pregnancy loss (<12 weeks) were estimated, separately, by year of pregnancy
      conception (limited to 1990-2011 to ensure a sufficient sample of pregnancies for
      each year and maternal age group) using log-Binomial and Poisson models, adjusted
      for maternal- and pregnancy-related factors. RESULTS: Among all self-reported
      pregnancies, excluding induced terminations, the risk of pregnancy loss was 19.7%
      and early pregnancy loss was 13.5% during 1990-2011. Risk of pregnancy loss
      increased by a relative 2% (rate ratio [RR] 1.02, 95% confidence interval [CI]
      1.01, 1.02) per year in unadjusted models and 1% per year (RR 1.01, 95% CI 1.00,
      1.02) during 1990-2011, after adjustment for maternal characteristics and
      pregnancy-related factors. In general, trends were similar for early pregnancy
      loss. CONCLUSION: From 1990 to 2011, risk of self-reported pregnancy loss
      increased among US women. Further work is needed to better understand the drivers
      of this increase in reported pregnancy loss in the US.

PMID- 29053190
TI  - Quantitative mesophyll parameters rather than whole-leaf traits predict response
      of C3 steppe plants to aridity.
AB  - We studied the impact of aridity on leaf and mesophyll traits in dominant and
      very abundant plant species of Eurasian steppe plant communities. We covered a
      500-km latitudinal gradient across three vegetation zones in the Volga region of
      southern European Russia. Whole-leaf traits, volumetric fractions of leaf
      tissues, quantitative parameters of photosynthetic cells and chloroplasts, and
      chlorophyll, carbon (C) and nitrogen (N) contents were analyzed and related to
      plant functional type (PFT), type of mesophyll anatomy, phylogeny and climate
      aridity. The proportions of prevailing PFTs in the communities, such as C3
      monocots, C3 dicots with dorsiventral and isopalisade anatomy and C4 dicots,
      changed with increasing aridity which influenced the whole-leaf parameters and
      tissue composition in the leaf. Leaf mass per unit area and leaf thickness
      slightly increased along the aridity gradient, but the most significant changes
      were observed in the mesophyll. Mesophyll cell surface area, chloroplast number
      and chloroplast surface area per unit leaf area were higher in C3 plants growing
      in the desert steppe compared with those of the forest steppe, while chlorophyll
      content per single chloroplast and per unit N content as well chlorophyll a/b
      ratio decreased. Our results identify a suite of mesophyll traits as a typical
      'syndrome' of increasingly drought-adapted steppe plants.

PMID- 29053189
TI  - Pilot screening study of targeted genetic polymorphisms for association with
      seasonal influenza hospital admission.
AB  - Host response to influenza is highly variable, suggesting a potential role of
      host genetic variation. To investigate the host genetics of severe influenza in a
      targeted fashion, 32 single nucleotide polymorphisms (SNPs) within viral immune
      response genes were evaluated for association with seasonal influenza
      hospitalization in an adult study population with European ancestry. SNP allele
      and genotype frequencies were compared between hospitalized influenza patients
      (cases) and population controls in a case-control study that included a discovery
      group (26 cases and 993 controls) and two independent, validation groups (1 with
      84 cases and 4076 controls; the other with 128 cases and 9187 controls). Cases
      and controls had similar allele frequencies for variant rs12252 in interferon
      inducible transmembrane protein 3 (IFITM3) (P > 0.05), and the study did not
      replicate the previously reported association of rs12252 with hospitalized
      influenza. In the discovery group, the preliminary finding of an association with
      a nonsense polymorphism (rs8072510) within the schlafen family member 13 (SFLN13)
      gene (P = 0.0099) was not confirmed in either validation group. Neither rs12252
      nor rs8072510 showed an association according to the presence of clinical risk
      factors for influenza complications (P > 0.05), suggesting that these factors did
      not modify associations between the SNPs and hospitalized influenza. No other
      SNPs showed a statistically significant association with hospitalized influenza.
      Further research is needed to identify genetic factors involved in host response
      to seasonal influenza infection and to assess whether rs12252, a low-frequency
      variant in Europeans, contributes to influenza severity in populations with
      European ancestry.

PMID- 29053192
TI  - Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral
      ischaemia in mice through reducing excessive tonic GABA release from reactive
      astrocytes.
AB  - Mechanisms underlying functional recovery after stroke are little known, and
      effective drug intervention during the delayed stage is desirable. One potential
      drug target, the protein-protein interaction between neuronal nitric oxide
      synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to
      acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation
      induced by microinjection of a recombinant fusion protein, Tat-nNOS-N1-133 , or
      systemic administration of a small-molecule, ZL006, from day 4 to day 10 after
      photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri
      infarct cortex and ameliorated motor functional outcome. We also demonstrated
      improved neuroplasticity including increased dendrite spine density and
      synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95
      dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4
      (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex.
      The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted
      function recovery, suggesting that increased tonic inhibition in the peri-infarct
      cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes.
      Treatments with Tat-nNOS-N1-133 or ZL006 after ischaemia inhibited astrocyte
      activation and GABA production, prevented the reversal of GAT-3/4, and
      consequently decreased excessive tonic inhibition and ameliorated functional
      outcome. The underlying molecular mechanisms were associated with epigenetic
      inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression
      through reduced NO production. The nNOS-PSD-95 interaction is thus a potential
      target for functional restoration after stroke and ZL006, a small molecule
      inhibitor of this interaction, is a promising pharmacological lead compound.
      Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29053191
TI  - Perceived stress is associated with smaller hippocampal volume in adolescence.
AB  - Perceived stress has been associated with decreased hippocampal, amygdala, and
      prefrontal cortex volume, as well as decreased memory and executive functioning
      performance in adulthood. Parents' perceived stress has been linked to decreased
      hippocampal volume in young children. However, no studies have investigated the
      links between self-perceived stress and brain structure or function in
      adolescents. Additionally, findings from previous research with younger or older
      samples are inconsistent, likely in part due to inconsistencies in participants'
      age range. In this study, we investigated the associations among self-perceived
      stress, family socioeconomic factors (family income, parental education),
      subcortical (hippocampus, amygdala) volumes, prefrontal cortical thickness and
      surface area, and memory and executive functioning performance in adolescents.
      One hundred and forty-three participants (12-20 years old) were administered a
      cognitive battery, a questionnaire to assess perceived stress, and a structural
      MRI scan. Higher levels of perceived stress were associated with decreased
      adolescent hippocampal volume. This study provides empirical evidence of how
      experience may shape brain development in adolescence-a period of plasticity
      during which it may be possible to intervene and prevent negative developmental
      outcomes.

PMID- 29053193
TI  - Body mass index at adolescence and risk of noncardia gastric cancer in a cohort
      of 1.79 million men and women.
AB  - BACKGROUND: This study assessed adolescent predictors of noncardia gastric cancer
      (NCGC) with a focus on the body mass index (BMI) in late adolescence. METHODS:
      This study analyzed a cohort of 1,087,358 Israeli Jewish males and 707,212
      Israeli Jewish females who underwent a compulsory physical examination between
      the ages of 16 and 19 years from 1967 to 2002. By linkage to the national cancer
      registry, participants were followed for NCGC through December 31, 2012. With a
      median follow-up of 23 years, 515 NCGC cases occurred (379 men and 136 women),
      and the median age was 47.0 years (interquartile range, 39.3-53.4 years).
      Multivariate-adjusted Cox regression was used to estimate hazard ratios (HRs) for
      NCGC according to the US Centers for Disease Control and Prevention BMI
      percentiles at the baseline (normal weight, 5th to <85th percentile; overweight,
      85th to <95th percentile; and obesity, >=95th percentile) as well as the country
      of birth, residential socioeconomic status (SES), and education. RESULTS: In
      comparison with normal weight, adolescent obesity, but not overweight, was
      associated in both men and women with the risk of subsequent NCGC (unadjusted HR,
      1.95; 95% confidence interval [CI], 1.25-3.06; adjusted HR, 1.78; 95% CI, 1.12
      2.83). Immigration from the former Soviet Union (FSU), a low education level, and
      a low residential SES were also associated with the risk for NCGC with adjusted
      HRs of 2.67 (95% CI, 1.86-3.83), 1.85 (95% CI, 1.53-2.25), and 1.48 (95% CI, 1.13
      1.93), respectively. CONCLUSIONS: The findings suggest that adolescent obesity,
      but not overweight, is associated with an increased risk for NCGC. Immigration
      from the FSU, a low residential SES, and a low education level are also
      significantly associated with the risk for NCGC. Cancer 2018;124:356-63. (c) 2017
      American Cancer Society.

PMID- 29053195
TI  - Correction.

PMID- 29053194
TI  - Gold and Hairpin DNA Functionalization of Upconversion Nanocrystals for Imaging
      and In Vivo Drug Delivery.

PMID- 29053197
TI  - Correction.

PMID- 29053198
TI  - Correction.

PMID- 29053199
TI  - Correction.

PMID- 29053200
TI  - Letter from Hong Kong.

PMID- 29053201
TI  - Changes in pulmonary artery systolic pressure and right ventricular function in
      patients with end-stage renal disease on maintenance dialysis.
AB  - BACKGROUND AND AIMS: Pulmonary hypertension is common in patients with end-stage
      renal disease, and portends a poor prognosis. There are little data in this
      population, and previous studies have not evaluated quantitative changes in
      hemodynamics over time while on maintenance dialysis. This study sought to
      estimate changes in pulmonary artery systolic pressure (PASP) and right
      ventricular function over time, and to predict PASP change using clinical
      variables routinely available at time of initial measurement, in patients on
      maintenance dialysis. METHODS: We retrospectively studied patients with end-stage
      renal disease at a university-affiliated dialysis center who had two separate
      echocardiograms 1-4 years apart. RESULTS: Seventy-six patients (65 hemodialysis,
      11 peritoneal dialysis) were included. PASP was estimated by echocardiography.
      Baseline PASP was predicted by left-sided valvular disease, anemia, COPD, left
      ventricular mass index, and hemodialysis modality (p=0.07 for modality). Average
      increase in PASP was 2.41 mmHg per year. Higher rates of PASP change were
      predicted by E/e' ratio by tissue doppler on echocardiogram, diabetes mellitus,
      low LV mass, and left-sided valvular heart disease (p=0.07 for valvular disease).
      Patients with higher PASP had higher incidence of new-onset right ventricular
      dysfunction. CONCLUSION: In patients with end-stage renal disease, PASP increases
      over time. Changes are moderately predictable. Higher PASP predicted development
      of right ventricular dysfunction.

PMID- 29053202
TI  - Treatment satisfaction with ITCA 650, a novel drug-device delivering continuous
      exenatide, versus twice-daily injections of exenatide in type 2 diabetics using
      metformin.
AB  - AIMS: To evaluate treatment satisfaction in patients with type 2 diabetes (T2D)
      not adequately controlled by metformin, randomized to ITCA 650 (continuous
      exenatide in osmotic mini-pump) vs twice-daily exenatide injections (Ex-BID).
      MATERIALS AND METHODS: The Diabetes Medication Satisfaction Tool (DM-SAT) was
      administered and assessments were made at baseline, Week 8 and Week 20 during a
      24-week open-label phase 2 trial. In Stage I (Weeks 1-12), 155 patients,
      comprising the ITT population, were randomized to 3 groups: ITCA 650 20 MUg/day,
      ITCA 650 40 MUg/day and Ex-BID 10 MUg BID. In Stage II (Weeks 13-24), ITCA 650
      groups were re-randomized to either remain on the Stage I dose or receive a
      higher dose. Patients treated with Ex-BID were randomized to 40 or 60 MUg/day
      ITCA 650. RESULTS: Patients using ITCA 650 reported significant increases in
      overall treatment satisfaction by Week 8 vs those using Ex-BID (P < .01), despite
      similar clinical efficacy and overall rates of nausea. During Stage II, further
      improvement in HbA1c and weight were seen after 3-fold dose escalation of ITCA
      650 and treatment satisfaction was maintained. When patients using Ex-BID were
      switched to ITCA 650, treatment satisfaction increased and reached levels similar
      to those initially treated with ITCA 650. Neither GI side effects of nausea
      and/or vomiting, nor the procedure to sub-dermally place ITCA 650, significantly
      impacted treatment satisfaction scores. CONCLUSION: ITCA 650 added to metformin
      for patients with T2D, and for those who switched to ITCA 650 from Ex-BID,
      meaningfully improved glucose control and significantly increased overall
      treatment satisfaction.

PMID- 29053203
TI  - Preoperative weight loss with glucagon-like peptide-1 receptor agonist treatment
      predicts greater weight loss achieved by the combination of medical weight
      management and bariatric surgery in patients with type 2 diabetes: A longitudinal
      analysis.
AB  - We examined the relationship between weight changes after preoperative glucagon
      like peptide-1 receptor agonist (GLP-1RA) treatment and weight changes from the
      start of medical weight management (MWM) until 12 months after bariatric surgery
      in patients with type 2 diabetes in a retrospective cohort study. A total of 45
      patients (64.4% women, median [interquartile range] age 49 [45-60] years) were
      included. The median (interquartile range) weight loss from start of MWM until 12
      months post-surgery was 17.9% (13.0%-29.3%). GLP-1RA treatment during MWM
      resulted in 5.0% (1.9%-7.7%) weight loss. Weight loss during GLP-1RA treatment
      predicted weight loss from the start of MWM until 12 months post-surgery, but not
      postoperative weight loss after adjustment. The proportion of weight loss from
      start of MWM to 12 months post-surgery attributed to GLP-1RA treatment was
      negatively associated with that attributed to surgery, after adjustment. In
      conclusion, weight change after GLP-1RA treatment predicted the weight loss
      achieved by a combination of MWM and bariatric surgery, but not weight loss
      induced by surgery only. Failure to lose weight after GLP-1RA treatment should
      not be considered a barrier to undergoing bariatric surgery.

PMID- 29053204
TI  - XEN-45 collagen implant for the treatment of uveitic glaucoma.
AB  - IMPORTANCE: The XEN-45 implant, a hydrophilic collagen implant which drains
      aqueous to the subconjunctival space, has not been investigated in the context of
      uveitic glaucoma. BACKGROUND: To determine the safety and efficacy of the XEN-45
      collagen implant in eyes with uveitic glaucoma. DESIGN: Exploratory prospective
      case series. PARTICIPANTS: patients with medically uncontrolled uveitic glaucoma.
      METHODS: Twenty-four consecutive patients (mean age +/- standard deviation [SD] =
      45.3 +/- 18.1 years) were implanted with the XEN-45 implant. MAIN OUTCOME
      MEASURES: The primary outcome measure was intraocular pressure (IOP) reduction at
      12 months as compared to baseline. Secondary outcome measures included ocular
      hypotensive medication use at 12 months, the requirement for further glaucoma
      surgery and failure. Intraoperative and postoperative complications were
      documented. RESULTS: The baseline mean +/- SD IOP was 30.5 +/- 9.8 mmHg and the
      mean +/- SD number of glaucoma medications required was 3.3 +/- 0.8. In 20 eyes
      (83.3%) in whom conventional glaucoma surgery was originally perceived to be
      inevitable, further surgery was not required after XEN-45 implantation. The mean
      IOP was reduced by 60.2% from baseline to 12.2 +/- 3.1 mmHg and mean medication
      usage was reduced to 0.4 +/- 0.9 at 12 months (both P < 0.001). One patient had
      hypotony persisting beyond 2 months that required surgical revision and one
      patient developed blebitis. The 12-month cumulative Kaplan-Meier survival
      probability was 79.2%. CONCLUSIONS AND RELEVANCE: The XEN-45 implant is effective
      for the treatment of patients with medically uncontrolled uveitic glaucoma.
      Potentially sight-threatening complications, including bleb-related ocular
      infection and persistent hypotony, may occur.

PMID- 29053205
TI  - Anal encirclement: a surgical technique for faecal incontinence in patients who
      are not good candidates for more invasive surgery - a video vignette.

PMID- 29053206
TI  - Clinical and microbiological profile of Pseudomonas aeruginosa keratitis admitted
      to a New Zealand tertiary centre.

PMID- 29053207
TI  - Dipeptidyl peptidase-4 inhibitors moderate the risk of genitourinary tract
      infections associated with sodium-glucose co-transporter-2 inhibitors.
AB  - Genitourinary tract infections (GUTIs) are the most common adverse event (AE)
      occurring during therapy with sodium-glucose co-transporter-2 (SGLT2) inhibitors.
      We evaluated whether dipeptidyl peptidase-4 inhibitors moderate the risk of GUTI
      during SGLT2 inhibitor therapy, using two approaches. First, we screened the
      literature for randomized controlled trials (RCTs) directly comparing the
      frequency of GUTIs in patients receiving DPP-4 inhibitor/SGLT2 inhibitor
      combination therapy vs those receiving an SGLT2 inhibitor only. In the five
      trials we retrieved, the pooled risk ratio for genital tract infections (GTIs) in
      patients on DPP-4 inhibitor/SGLT2 inhibitor combination therapy vs those on SGLT2
      inhibitors alone was 0.51 (95% confidence interval [CI] 0.28-0.92). Second, we
      found that within the Food and Drug Administration AE Reporting System, the
      frequency of GUTIs among reports listing both SGLT2 and DPP-4 inhibitors as
      suspect or concomitant drugs was significantly lower than among reports listing
      SGLT2 inhibitors without DPP-4 inhibitors, with a proportional reporting ratio of
      0.74 (95% CI 0.61-0.90). In conclusion, in RCTs and in a large pharmacovigilance
      database, combination therapy with a DPP-4 inhibitor appears to reduce the
      frequency of G(U)TIs associated with SGLT2 inhibitors.

PMID- 29053208
TI  - Intermolecular Pummerer Coupling with Carbon Nucleophiles in Non-Electrophilic
      Media.
AB  - A new Pummerer-type C-C coupling protocol is introduced based on turbo
      organomagnesium amides, which unlike traditional Pummerer reactions, does not
      require strong electrophilic activators, engages a broad range of C(sp3 )-, C(sp2
      )-, and C(sp)-nucleophiles, and seamlessly integrates with C-H and C-X
      magnesiation. Given the central character of sulfur compounds in organic
      chemistry, this protocol allows access to unrelated carbonyls, olefins,
      organometallics, halides, and boronic esters through a single strategy.

PMID- 29053209
TI  - Laparoscopic extended right and transverse colectomy with completely
      intracorporeal ileo-descending anastomosis for obstructing colon carcinoma - a
      video vignette.

PMID- 29053210
TI  - A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology
      for the diagnosis of mesothelioma.
AB  - BACKGROUND: Homozygous deletion of 9p21 detected by fluorescence in situ
      hybridization (FISH) and loss of BRCA1-associated protein 1 (BAP1) expression
      detected by immunohistochemistry (IHC) are useful for the differentiation between
      malignant pleural mesothelioma (MPM) and reactive mesothelial hyperplasia. The
      authors previously described that IHC expression of the protein product of the
      methylthioadenosine phosphorylase (MTAP) gene, which is localized in the 9p21
      chromosomal region, was correlated with the deletion status of 9p21 FISH in MPM
      tissues. In the current study, the authors investigated whether a combination of
      MTAP and BAP1 IHC could distinguish MPM from reactive mesothelial cells (RMC) in
      cell blocks obtained from pleural effusions. METHODS: The authors examined IHC
      expression of MTAP and BAP1 in cell blocks obtained from pleural effusions of 45
      cases of MPM and 21 cases of reactive mesothelial hyperplasia. Furthermore, IHC
      expression of MTAP was compared with the deletion status of 9p21 FISH. RESULTS:
      MTAP and BAP1 IHC differentiated MPM from RMC with 100% specificity for both and
      sensitivities of 42.2% and 60.0%, respectively. The combination of MTAP and BAP1
      IHC yielded a sensitivity of 77.8%, which was higher than that of BAP1 IHC alone
      or 9p21 FISH alone (62.2%). Moreover, a high degree of concordance was observed
      between the results of MTAP IHC and 9p21 FISH in cell blocks. CONCLUSIONS: A
      combination of MTAP and BAP1 IHC in cell blocks from pleural effusions appears to
      be a reliable and useful method for differentiating MPM cells from RMC and can be
      used in the routine diagnosis of MPM. Cancer Cytopathol 2018;126:54-63. (c) 2017
      American Cancer Society.

PMID- 29053211
TI  - V-Y advancement flap reconstruction for anal stricture - a video vignette.

PMID- 29053212
TI  - Creation of "Rose Petal" and "Lotus Leaf" Effects on Alumina by Surface
      Functionalization and Metal-Ion Coordination.
AB  - Functional differences between superhydrophobic surfaces, such as lotus leaf and
      rose petals, are due to the subtle architectural features created by nature.
      Mimicry of these surfaces with synthetic molecules continues to be fascinating as
      well as challenging. Herein, we demonstrate how inherently hydrophilic alumina
      surface can be modified to give two distinct superhydrophobic behaviors.
      Functionalization of alumina with an organic ligand resulted in a rose-petal-like
      surface (water pinning) with a contact angle of 145 degrees  and a high contact
      angle hysteresis (+/-69 degrees ). Subsequent interaction of the ligand with Zn2+
      resulted in a lotus-leaf-like surface with water rolling behavior owing to high
      contact angle (165 degrees ) and low-contact-angle-hysteresis (+/-2 degrees ). In
      both cases, coating of an aromatic bis-aldehyde with alkoxy chain substituents
      was necessary to emulate the nanowaxy cuticular feature of natural
      superhydrophobic materials.

PMID- 29053213
TI  - A De Novo Heterodimeric Due Ferri Protein Minimizes the Release of Reactive
      Intermediates in Dioxygen-Dependent Oxidation.
AB  - Metalloproteins utilize O2 as an oxidant, and they often achieve a 4-electron
      reduction without H2 O2 or oxygen radical release. Several proteins have been
      designed to catalyze one or two-electron oxidative chemistry, but the de novo
      design of a protein that catalyzes the net 4-electron reduction of O2 has not
      been reported yet. We report the construction of a diiron-binding four-helix
      bundle, made up of two different covalently linked alpha2 monomers, through click
      chemistry. Surprisingly, the prototype protein, DF-C1, showed a large divergence
      in its reactivity from earlier DFs (DF: due ferri, two iron). DFs release the
      quinone imine and free H2 O2 in the oxidation of 4-aminophenol in the presence of
      O2 , whereas FeIII -DF-C1 sequesters the quinone imine into the active site, and
      catalyzes inside the scaffold an oxidative coupling between oxidized and reduced
      4-aminophenol. The asymmetry of the scaffold allowed a fine-engineering of the
      substrate binding pocket, that ensures selectivity.

PMID- 29053214
TI  - Herbicide discovery in light of rapidly spreading resistance and ever-increasing
      regulatory hurdles.
AB  - According to the United Nations, the global population is expected to grow to
      almost 10 billion people in 2050. This means that the demand for food, feed and
      fiber will double while at the same time, agriculture is being challenged by a
      scarcity of water, global warming, less land available for farming, protection of
      natural habitats, a demand for biodiversity on farms and other factors. In
      addition, crop protection products are under pressure from rapidly spreading
      resistance and increasing regulatory requirements. Many regulatory bodies are
      also moving away from a risk assessment approach to a more hazard-based approach
      to grant registrations. Nevertheless, chemical crop protection compounds remain
      attractive and necessary to combat pests, particularly weeds. Industry has
      increased its efforts to find new molecules that are highly biologically
      effective on target species, including resistant populations, but safe for non
      target organisms. To manage resistance in the future, a diverse toolbox is needed
      that includes herbicides with a variety of different chemistries and modes of
      action, combined with non-chemical measures in integrated systems. However,
      discovering a herbicide and getting it registered and to the market is an
      extremely complex endeavor full of risk, much of it incalculable. (c) 2017
      Society of Chemical Industry.

PMID- 29053216
TI  - "Suspicious" salivary gland FNA: Risk of malignancy and interinstitutional
      variability.
AB  - BACKGROUND: Fine-needle aspiration (FNA) cytology is well accepted as a safe,
      reliable, minimally invasive, and cost-effective method for the diagnosis of
      salivary gland lesions. Salivary gland neoplasms are often difficult to diagnose
      because of morphologic heterogeneity and a variety of epithelial metaplastic
      changes. Hence, a number of salivary gland FNA specimens yield indeterminate
      results. For indeterminate FNA specimens, the suspicious-for-malignancy (SFM)
      category is used when a specific neoplasm falls short in quantity or quality for
      the criteria for malignancy. Therefore, the findings are not sufficient for a
      conclusive diagnosis of malignancy. METHODS: This study was designed to evaluate
      the risk of malignancy (ROM) for the SFM group at 5 tertiary medical centers
      worldwide with the aforementioned criteria. Among 12,606 salivary gland FNA cases
      between 1997 and 2014, 276 (2.2%) were reported to be SFN. Specifically, 114
      suspicious cases (41%) had histological follow-up. RESULTS: Histological follow
      up of the 114 suspicious cases showed 95 malignant tumors indicating a risk of
      malignancy (ROM) of 83.3%. The ROM varied between 74% and 88% for the 5
      participating institutions, and a Fisher's exact test with significance set to
      p<.05 showed no significant difference in ROM among the institutions (p = .78).
      CONCLUSIONS: Overall, 83.3% of SFM salivary gland FNA specimens turned out to be
      malignant; there was no significant interinstitutional variability in the ROMs.
      The SFM category for salivary gland FNA is very homogeneous, and the ROMs are
      quite similar worldwide. Cancer Cytopathol 2018;126:94-100. (c) 2017 American
      Cancer Society.

PMID- 29053218
TI  - Pelvic floor reconstruction with bilateral gracilis flaps following extralevator
      abdominoperineal excision - a video vignette.

PMID- 29053217
TI  - Behavioral control by striatal adenosine A2A -dopamine D2 receptor heteromers.
AB  - G protein-coupled receptors (GPCR) exhibit the ability to form receptor complexes
      that include molecularly different GPCR (ie, GPCR heteromers), which endow them
      with singular functional and pharmacological characteristics. The relative
      expression of GPCR heteromers remains a matter of intense debate. Recent studies
      support that adenosine A2A receptors (A2A R) and dopamine D2 receptors (D2 R)
      predominantly form A2A R-D2 R heteromers in the striatum. The aim of the present
      study was evaluating the behavioral effects of pharmacological manipulation and
      genetic blockade of A2A R and D2 R within the frame of such a predominant
      striatal heteromeric population. First, in order to avoid possible strain-related
      differences, a new D2 R-deficient mouse with the same genetic background (CD-1)
      than the A2A R knock-out mouse was generated. Locomotor activity, pre-pulse
      inhibition (PPI) and drug-induced catalepsy were then evaluated in wild-type, A2A
      R and D2 R knock-out mice, with and without the concomitant administration of
      either the D2 R agonist sumanirole or the A2A R antagonist SCH442416. SCH442416
      mediated locomotor effects were demonstrated to be dependent on D2 R signaling.
      Similarly, a significant dependence on A2A R signaling was observed for PPI and
      for haloperidol-induced catalepsy. The results could be explained by the
      existence of one main population of striatal postsynaptic A2A R-D2 R heteromers,
      which may constitute a relevant target for the treatment of Parkinson's disease
      and other neuropsychiatric disorders.

PMID- 29053215
TI  - Identification of barriers to insulin therapy and approaches to overcoming them.
AB  - Poor glycaemic control in type 2 diabetes (T2D) is a global problem despite the
      availability of numerous glucose-lowering therapies and clear guidelines for T2D
      management. Tackling clinical or therapeutic inertia, where the person with
      diabetes and/or their healthcare providers do not intensify treatment regimens
      despite this being appropriate, is key to improving patients' long-term outcomes.
      This gap between best practice and current level of care is most pronounced when
      considering insulin regimens, with studies showing that insulin
      initiation/intensification is frequently and inappropriately delayed for several
      years. Patient- and physician-related factors both contribute to this resistance
      at the stages of insulin initiation, titration and intensification, impeding
      achievement of optimal glycaemic control. The present review evaluates the
      evidence and reasons for this delay, together with available methods for
      facilitation of insulin initiation or intensification.

PMID- 29053219
TI  - Gum chewing aids bowel function return and analgesic requirements after bowel
      surgery: a randomized controlled trial.
AB  - AIM: The aim was to compare the effectiveness of chewing sugar-free gum after
      bowel resection on bowel function and length of stay. METHOD: This was a
      randomized controlled trial of patients undergoing elective open or laparoscopic
      bowel surgery, who were allocated into two groups: a chewing gum group (CG); or a
      nonchewing gum group (NG). Primary outcomes were time to discharge (length of
      hospital stay [LOS]), time to first flatus (TFF) and time to first bowel motion
      (TBM). Secondary outcomes were complication rates, pain and total morphine
      equivalent (TMEq) medication for 7 days after the procedure. RESULTS: Between
      2010 and 2013, 162 patients were randomized; four were excluded, leaving 158 in
      the study (82 in the CG and 76 in the NG). There was no difference in LOS between
      the CG (5.8 days) and the NG (6.1 days) (P = 0.403) or in the median TFF between
      the CG (42.0 h) and the NG (58.0 h) (P = 0.076). The median TBM was lower in the
      CG (40.0 h) than in the NG (90.0 h) (P = 0.002). There was no difference in intra
      operative complications between the CG (9%) and the NG (9%) (P = 0.901) or in
      early postoperative complications (44% for CG and 55% for NG) (P = 0.131). There
      was no difference in TMEq at 24 h postprocedure, but the CG had reduced TMEq from
      days 2 to 7 post procedure and for the 7-day total. Pain was higher among
      patients in the NG on day 3. CONCLUSION: Chewing sugar-free gum resulted in an
      earlier return to bowel function and decreased analgesic requirements. There was
      no decrease in overall LOS or postoperative complications.

PMID- 29053220
TI  - Adalimumab and postoperative complications of elective intestinal resections in
      Crohn's disease: a propensity score case-matched study.
AB  - BACKGROUND: data are scarce regarding the effect of preoperative Adalimumab (ADA)
      in postoperative complications in Crohn's disease (CD) patients. AIM: to compare
      the rates of postoperative complications after intestinal resections in CD, with
      and without previous exposure to ADA. METHOD: case-matched retrospective
      observational study of patients submitted to intestinal resections for CD. The
      patients were allocated to 2 groups, according to their previous exposure to ADA
      before surgery. The patients under ADA therapy were matched with controls
      (patients without previous biologics) with the propensity score method (PSM),
      according to age at surgery, CD location (Montreal L) and phenotype (Montreal B).
      Medical and surgical complications were compared. RESULTS: 123 patients were
      initially considered, 71 with previous biologics (32 under ADA therapy) and 52
      without. The PSM selected 25 ADA patients to be matched with 25 controls from the
      non-biologics group. There was no difference regarding overall surgical
      complications (40% in the control vs 36% in the ADA group; p = 1.0000) or medical
      complications (36% vs 12% in the control and ADA groups, respectively; p =
      0.095). In univariate analysis, previous ADA was not considered a risk factor for
      higher postoperative complication rates. Stomas were considered a risk factor for
      surgical complications, and previous steroids were associated to higher medical
      complication rates. CONCLUSIONS: preoperative ADA did not influence the rates of
      medical and surgical complications after elective intestinal resections for CD.
      This was the first study to include exclusively patients under ADA therapy. This
      article is protected by copyright. All rights reserved.

PMID- 29053221
TI  - Totally extraperitoneal approach for scrotal cystocele - a video vignette.

PMID- 29053222
TI  - Techniques of tension-free colorectal/anal anastomosis in a reoperative abdomen -
      a video vignette.

PMID- 29053224
TI  - Programmed death-ligand 1 testing of lung cancer cytology specimens obtained with
      bronchoscopy.
AB  - BACKGROUND: Programmed death-ligand 1 (PD-L1) expression testing is recommended
      by guidelines for patients with advanced non-small cell lung cancer (NSCLC). The
      primary objective of the current study was to determine the success rate of PD-L1
      testing from cytology cell block samples obtained by bronchoscopic needle
      aspiration. The secondary objective was the assessment of the difference in
      specimen adequacy acquired via needles of different gauges. METHODS: Patients
      with NSCLC who underwent bronchoscopic needle aspirations for which PD-L1 testing
      was requested between November 1, 2016, and February 6, 2017, were included in
      the current analysis. Patients underwent needle aspiration from intrathoracic
      adenopathy or a pulmonary lesion. Rapid on-site cytology evaluation was performed
      in all cases. PD-L1 immunohistochemistry was performed using the Abcam anti-PD-L1
      antibody 28.8 clone on cell block specimen. RESULTS: A total of 22 patients had
      PD-L1 testing requested on needle cytology samples obtained via bronchoscopy at
      the time of initial diagnosis (81.8%) and for progression of disease (18.2%).
      Twenty patients (90.9%) underwent successful PD-L1 testing. Sample acquisition
      was via endobronchial ultrasound-guided transbronchial needle aspiration in 72.7%
      of patients, endobronchial needle aspiration in 18.2% of patients, and peripheral
      nodule needle aspiration in 9.1% of patients. There was no statistical difference
      in PD-L1 test success rates between sample methods (P = .99) or needle sizes (P =
      1.00). CONCLUSIONS: Bronchoscopically obtained cytology needle-based samples are
      adequate for PD-L1 testing in patients with NSCLC. There was no difference noted
      between different needle sizes with regard to adequacy for PD-L1 testing. These
      findings are relevant for clinicians caring for patients with lung cancer because
      a vast majority of patients with advanced NSCLC are diagnosed by bronchoscopic
      needle-based techniques using a variety of commercially available needles. Cancer
      Cytopathol 2018;126:122-8. (c) 2017 American Cancer Society.

PMID- 29053223
TI  - The utility of adaptive eLearning in cervical cytopathology education.
AB  - BACKGROUND: Adaptive eLearning allows students to experience a self-paced,
      individualized curriculum based on prior knowledge and learning ability. METHODS:
      The authors investigated the effectiveness of adaptive online modules in teaching
      cervical cytopathology. eLearning modules were created that covered basic
      concepts in cervical cytopathology, including artifacts and infections, squamous
      lesions (SL), and glandular lesions (GL). The modules used student responses to
      individualize the educational curriculum and provide real-time feedback.
      Pathology trainees and faculty from the authors' institution were randomized into
      2 groups (SL or GL), and identical pre-tests and post-tests were used to compare
      the efficacy of eLearning modules versus traditional study methods (textbooks and
      slide sets). User experience was assessed with a Likert scale and free-text
      responses. RESULTS: Sixteen of 17 participants completed the SL module, and 19 of
      19 completed the GL module. Participants in both groups had improved post-test
      scores for content in the adaptive eLearning module. Users indicated that the
      module was effective in presenting content and concepts (Likert scale [from 1 to
      5], 4.3 of 5.0), was an efficient and convenient way to review the material
      (Likert scale, 4.4 of 5.0), and was more engaging than lectures and texts (Likert
      scale, 4.6 of 5.0). Users favored the immediate feedback and interactivity of the
      module. Limitations included the inability to review prior content and slow
      upload time for images. Learners demonstrated improvement in their knowledge
      after the use of adaptive eLearning modules compared with traditional methods.
      CONCLUSIONS: Overall, the modules were viewed positively by participants.
      Adaptive eLearning modules can provide an engaging and effective adjunct to
      traditional teaching methods in cervical cytopathology. Cancer Cytopathol
      2018;126:129-35. (c) 2017 American Cancer Society.

PMID- 29053225
TI  - Histological outcomes of anal high-grade cytopredictions.
AB  - BACKGROUND: Longitudinal studies of histological outcomes after anal cytological
      screening in men who have sex with men (MSM) are rare. This study measured the
      positive predictive values (PPVs) of each level of baseline cytological
      abnormality in MSM in Sydney, Australia, over a 12-month period. METHODS: The
      Study of the Prevention of Anal Cancer is a 3-year prospective study of the
      natural history of anal human papillomavirus infection in MSM at least 35 years
      old. For each participant with a baseline cytological abnormality, the worst
      histology was recorded at the baseline high-resolution anoscopy and at 6 and 12
      months. PPVs for a histological high-grade squamous intraepithelial lesion (HSIL)
      diagnosis were calculated for each level of baseline cytological abnormality at
      each time point. RESULTS: Among 424 men who completed 3 visits, the PPV of a
      cytological HSIL increased from 71.6% at the baseline to 86.4% at 6 months and to
      92.6% at 12 months (P < .001). For cytological atypical squamous cells, cannot
      rule out high-grade squamous intraepithelial lesion (ASC-H), the PPV increased
      from 51.5% at the baseline to 69.7% at 6 months and to 75.8% at 12 months (P =
      .004). At each time point, the PPV of a cytological HSIL was significantly higher
      than the PPV of ASC-H. The PPV of low-grade cytology reports was significantly
      lower than the PPV of ASC-H at each time point. CONCLUSIONS: In a cohort of MSM,
      a baseline histological HSIL diagnosis after an HSIL cytoprediction is high, and
      it increases with further examinations over the course of 12 months. Lower levels
      of cytological abnormalities have significantly lower PPVs. These data can inform
      patient management and the quality assessment of each aspect of the screening
      pathway. Cancer Cytopathol 2018;126:136-44. (c) 2017 American Cancer Society.

PMID- 29053226
TI  - Cover Image, Volume 173A, Number 11, November 2017.
AB  - The cover image, by Cristina M. Justice et al., is based on the Original Article
      A Variant Associated with Sagittal Nonsydromic Craniosynostosis Alters the
      Regulatory Function of a Non-Coding Element, DOI: 10.1002/ajmg.a.38392. Photo
      Credit: Blake Carrington (NIH/NHGRI).

PMID- 29053227
TI  - Cautious approach to genome editing urged: Statement says to hold off on clinical
      use but supports in vitro research.

PMID- 29053229
TI  - Opitz award paper describes skeletal disorder: Researcher characterizes clinical
      disease in detail.

PMID- 29053230
TI  - A randomized controlled trial of four different regimes of biofeedback programme
      in the treatment of faecal incontinence.
AB  - AIM: Biofeedback is an established, effective and non-invasive treatment for
      faecal incontinence (FI). The aim was to compare the effectiveness of four
      different biofeedback treatment regimes. METHOD: This was a randomized control
      trial of patients with FI, stratified into two groups (metropolitan and rural)
      and then randomized into two subgroups (groups 1 and 2 within metropolitan,
      groups 3 and 4 within rural) with varying face-to-face and telephone biofeedback
      components. All patients received standardized counselling and education, dietary
      modification and the use of anti-diarrhoeal medications. Group 1 received four
      monthly face-to-face biofeedback treatments, groups 2 and 3 received one face-to
      face biofeedback followed by telephone biofeedback and group 4 received a one-off
      face-to-face biofeedback treatment. Primary outcomes were patient-assessed
      severity of FI and quality of life as assessed by the 36-item Short Form Health
      Survey and direct questioning of objectives. Secondary outcomes included St
      Mark's incontinence score, anxiety, depression and anorectal physiology measures
      (resting, squeeze pressures; isotonic, isometric fatigue times). RESULTS: Between
      2006 and 2012, 351 patients were recruited. One patient died leaving 350 for
      analysis. 332 (95%) were women. Mean age was 60 (SD = 14). All groups had
      significant improvements in FI, quality of life, incontinence score and mental
      status (P < 0.001 each). There were no differences in improvements in FI between
      groups although patient satisfaction was less with reduced face-to-face contact.
      There were modest improvements in isotonic and isometric fatigue times suggesting
      improved sphincter endurance (both P < 0.001). CONCLUSION: Biofeedback is
      effective for FI. Although face-to-face and telephone biofeedback is not
      necessary to improve FI, it is important for patient satisfaction.

PMID- 29053231
TI  - Effects of common cold and concomitant administration of nasal decongestant on
      the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy
      participants: A randomized clinical trial.
AB  - AIMS: Nasal glucagon (NG) is a nasally-administered glucagon powder, absorbed
      through the nasal mucosa, designed for treatment of severe hypoglycaemia. This
      study evaluated the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of NG
      in otherwise healthy participants with common colds and after recovery from cold
      symptoms, with and without concomitant nasal decongestant. MATERIALS AND METHODS:
      This was a single-centre, open-label study. Cohort 1 participants (N = 18)
      received 2 doses of NG: one while experiencing nasal congestion and another after
      recovery from cold symptoms. Cohort 2 participants (N = 18), who also had colds
      with nasal congestion, received a single dose of NG 2 hours after treatment with
      the decongestant oxymetazoline. Total symptoms score and other safety measures
      were assessed before and after NG administration. RESULTS: NG was well tolerated,
      without serious adverse events. Common adverse events (transient lacrimation,
      nasal discomfort, rhinorrhea and nausea) were more frequent in both Cohorts 1 and
      2 during nasal congestion. Glucagon levels peaked 18 minutes post-dose and
      glucose levels peaked 30 to 42 minutes post-dose in all groups. Nasal congestion,
      with or without concomitant nasal decongestant, did not significantly affect PK
      of NG. Although glucose AUECs0-t was different between Cohort 1 with nasal
      congestion and Cohort 2, glucose concentrations at 30 minutes appeared similar in
      all groups. CONCLUSIONS: There were no clinically relevant differences in safety
      or PK/PD of NG associated with nasal congestion or concomitant administration of
      nasal decongestant, suggesting that NG can be used to treat severe hypoglycaemia
      in individuals experiencing nasal congestion.

PMID- 29053232
TI  - Generational Aspects of Medicare.

PMID- 29053233
TI  - Child Health and Household Resources in South Africa: Evidence from the Old Age
      Pension Program

PMID- 29053234
TI  - Career and Marriage in the Age of the Pill.

PMID- 29053235
TI  - Some Things Change.

PMID- 29053236
TI  - Sugar--What Should Be Done?

PMID- 29053238
TI  - Older Adults Affected by Gene Mutations When Taking Multiple Medications.

PMID- 29053237
TI  - The Well-Taylored Dentist

PMID- 29053239
TI  - School Sealant Programs a Cost-Effective Way to Prevent Childhood Caries.

PMID- 29053240
TI  - Cellulose Nanocrystals 'Offer Promising Approach for Bone Regeneration.'

PMID- 29053241
TI  - Temperature-Dependent Thermal Boundary Conductance of Monolayer MoS2 by Raman
      Thermometry.
AB  - The electrical and thermal behavior of nanoscale devices based on two-dimensional
      (2D) materials is often limited by their contacts and interfaces. Here we report
      the temperature-dependent thermal boundary conductance (TBC) of monolayer MoS2
      with AlN and SiO2, using Raman thermometry with laser-induced heating. The
      temperature-dependent optical absorption of the 2D material is crucial in such
      experiments, which we characterize here for the first time above room
      temperature. We obtain TBC ~ 15 MW m-2 K-1 near room temperature, increasing as ~
      T0.65 in the range 300-600 K. The similar TBC of MoS2 with the two substrates
      indicates that MoS2 is the "softer" material with weaker phonon irradiance, and
      the relatively low TBC signifies that such interfaces present a key bottleneck in
      energy dissipation from 2D devices. Our approach is needed to correctly perform
      Raman thermometry of 2D materials, and our findings are key for understanding
      energy coupling at the nanoscale.

PMID- 29053242
TI  - Environmental Effects on Zirconium Hydroxide Nanoparticles and Chemical Warfare
      Agent Decomposition: Implications of Atmospheric Water and Carbon Dioxide.
AB  - Zirconium hydroxide (Zr(OH)4) has excellent sorption properties and wide-ranging
      reactivity toward numerous types of chemical warfare agents (CWAs) and toxic
      industrial chemicals. Under pristine laboratory conditions, the effectiveness of
      Zr(OH)4 has been attributed to a combination of diverse surface hydroxyl species
      and defects; however, atmospheric components (e.g., CO2, H2O, etc.) and trace
      contaminants can form adsorbates with potentially detrimental impact to the
      chemical reactivity of Zr(OH)4. Here, we report the hydrolysis of a CWA simulant,
      dimethyl methylphosphonate (DMMP) on Zr(OH)4 determined by gas chromatography
      mass spectrometry and in situ attenuated total reflectance Fourier transform
      infrared spectroscopy under ambient conditions. DMMP dosing on Zr(OH)4 formed
      methyl methylphosphonate and methoxy degradation products on free bridging and
      terminal hydroxyl sites of Zr(OH)4 under all evaluated environmental conditions.
      CO2 dosing on Zr(OH)4 formed adsorbed (bi)carbonates and interfacial carbonate
      complexes with relative stability dependent on CO2 and H2O partial pressures.
      High concentrations of CO2 reduced DMMP decomposition kinetics by occupying
      Zr(OH)4 active sites with carbonaceous adsorbates. Elevated humidity promoted
      hydrolysis of adsorbed DMMP on Zr(OH)4 to produce methanol and regenerated free
      hydroxyl species. Hydrolysis of DMMP by Zr(OH)4 occurred under all conditions
      evaluated, demonstrating promise for chemical decontamination under diverse, real
      world conditions.

PMID- 29053244
TI  - Punctured Two-Dimensional Sheets for Harvesting Blue Energy.
AB  - The challenges of global climate change and the world's growing demand for energy
      have brought the need for new renewable energy sources to the top of the
      international community's agenda. We have known for many centuries that energy is
      released upon mixing seawater and freshwater, yet it was just a few decades ago
      that it became clear how this energy can be converted into electricity instead of
      heat. As a result, the blue energy rush has raised and set new strategies in
      different science and technology sectors, leading to the construction of a new
      generation of plants and other technological investments. Among many approaches,
      pressure-retarded osmosis has emerged as a promising method to collect the
      largest amount of produced blue energy. In this Perspective, we highlight the
      advances in the development of ultrathin membranes based on two-dimensional
      materials. We discuss the most relevant synthetic methods devised to generate
      atomically thin membranes for pressure-retarded osmosis and retarded
      electrodialysis applications, and we provide some critical views on the greatest
      challenges in this thrilling research area.

PMID- 29053243
TI  - Identification of the Biosynthetic Pathway for the Antibiotic Bicyclomycin.
AB  - Diketopiperazines (DKPs) make up a large group of natural products with diverse
      structures and biological activities. Bicyclomycin is a broad-spectrum DKP
      antibiotic with unique structure and function: it contains a highly oxidized
      bicyclic [4.2.2] ring and is the only known selective inhibitor of the bacterial
      transcription termination factor, Rho. Here, we identify the biosynthetic gene
      cluster for bicyclomycin containing six iron-dependent oxidases. We demonstrate
      that the DKP core is made by a tRNA-dependent cyclodipeptide synthase, and
      hydroxylations on two unactivated sp3 carbons are performed by two mononuclear
      iron, alpha-ketoglutarate-dependent hydroxylases. Using bioinformatics, we also
      identify a homologous gene cluster prevalent in a human pathogen Pseudomonas
      aeruginosa. We detect bicyclomycin by overexpressing this gene cluster and
      establish P. aeruginosa as a new producer of bicyclomycin. Our work uncovers the
      biosynthetic pathway for bicyclomycin and sheds light on the intriguing oxidation
      chemistry that converts a simple DKP into a powerful antibiotic.

PMID- 29053245
TI  - Generation and Characterization of Recombinant Antibody-like ADP-Ribose Binding
      Proteins.
AB  - ADP-ribosylation is an enzyme-catalyzed post-translational modification of
      proteins in which the ADP-ribose (ADPR) moiety of NAD+ is transferred to a
      specific amino acid in a substrate protein. The biological functions of ADP
      ribosylation are numerous and diverse, ranging from normal physiology to
      pathological conditions. Biochemical and cellular studies of the diverse forms
      and functions of ADPR require immunological reagents that can be used for
      detection and enrichment. The lack of a complete set of tools that recognize all
      forms of ADPR [i.e., mono-, oligo-, and poly(ADP-ribose)] has hampered progress.
      Herein, we describe the generation and characterization of a set of recombinant
      antibody-like ADP-ribose binding proteins, in which naturally occurring ADPR
      binding domains, including macrodomains and WWE domains, have been functionalized
      by fusion to the Fc region of rabbit immunoglobulin. These reagents, which
      collectively recognize all forms of ADPR with different specificities, are useful
      in a broad array of antibody-based assays, such as immunoblotting,
      immunofluorescent staining of cells, and immunoprecipitation. Observations from
      these assays suggest that the biology of ADPR is more diverse, rich, and complex
      than previously thought. The ARBD-Fc fusion proteins described herein will be
      useful tools for future exploration of the chemistry, biochemistry, and biology
      of ADP-ribose.

PMID- 29053246
TI  - Driving Chemical Reactions in Plasmonic Nanogaps with Electrohydrodynamic Flow.
AB  - Nanoparticles from colloidal solution-with controlled composition, size, and
      shape-serve as excellent building blocks for plasmonic devices and metasurfaces.
      However, understanding hierarchical driving forces affecting the geometry of
      oligomers and interparticle gap spacings is still needed to fabricate high
      density architectures over large areas. Here, electrohydrodynamic (EHD) flow is
      used as a long-range driving force to enable carbodiimide cross-linking between
      nanospheres and produces oligomers exhibiting sub-nanometer gap spacing over mm2
      areas. Anhydride linkers between nanospheres are observed via surface-enhanced
      Raman scattering (SERS) spectroscopy. The anhydride linkers are cleavable via
      nucleophilic substitution and enable placement of nucleophilic molecules in
      electromagnetic hotspots. Atomistic simulations elucidate that the transient
      attractive force provided by EHD flow is needed to provide a sufficient residence
      time for anhydride cross-linking to overcome slow reaction kinetics. This
      synergistic analysis shows assembly involves an interplay between long-range
      driving forces increasing nanoparticle-nanoparticle interactions and probability
      that ligands are in proximity to overcome activation energy barriers associated
      with short-range chemical reactions. Absorption spectroscopy and electromagnetic
      full-wave simulations show that variations in nanogap spacing have a greater
      influence on optical response than variations in close-packed oligomer geometry.
      The EHD flow-anhydride cross-linking assembly method enables close-packed
      oligomers with uniform gap spacings that produce uniform SERS enhancement
      factors. These results demonstrate the efficacy of colloidal driving forces to
      selectively enable chemical reactions leading to future assembly platforms for
      large-area nanodevices.

PMID- 29053247
TI  - Aggregation-Driven Controllable Plasmonic Transition of Silica-Coated Gold
      Nanoparticles with Temperature-Dependent Polymer-Nanoparticle Interactions for
      Potential Applications in Optoelectronic Devices.
AB  - Localized surface plasmon resonance (LSPR) effect relies on the shape, size, and
      dispersion state of metal nanoparticles and can potentially be employed in many
      applications such as chemical/biological sensor, optoelectronics, and
      photocatalyst. While complicated synthetic approaches changing shape and size of
      nanoparticles can control the intrinsic LSPR effect, here we show that
      controlling interparticle interactions with silica-coated gold nanoparticles
      (Au@SiO2 NPs) is a powerful approach, permitting wide range of optical bandwidth
      of gold nanoparticles with great stability. The interparticle interactions of
      Au@SiO2 NPs are controlled through concentration-, temperature-, and time
      dependent polymer-induced interactions. The polymer-induced interactions modulate
      the state of particle dispersion, resulting an effective plasmonic shift by more
      than 200 nm. We further explore the microstructure of particle aggregation and
      explain mechanisms of plasmonic shift based on the results of small-angle X-ray
      scattering (SAXS) and discrete dipole approximation (DDA) calculation. We show
      that an effective control of LSPR behavior is now available through trapped
      aggregation of Au@SiO2 NPs with temperature variation. We anticipate that the
      suggested strategy can be employed in many practical applications such as optical
      bioimaging and optoelectronic devices.

PMID- 29053248
TI  - In Vitro Evolution of Unmodified 16S rRNA for Simple Ribosome Reconstitution.
AB  - One of the largest challenges in the synthesis of artificial cells that can
      reproduce is in vitro assembly of ribosomes from in vitro synthesized rRNAs and
      proteins. In this study, to circumvent the post-transcriptional modification of
      16S rRNA for reconstitution of the fully active 30S subunit, we performed
      artificial evolution of 16S rRNA, which forms the functional 30S subunit without
      post-transcriptional modifications. We first established an in vitro selection
      scheme by combining the integrated synthesis, assembly, and translation (iSAT)
      system with the liposome sorting technique. After 15 rounds of selection cycles,
      we found one point mutation (U1495C) near the 3' terminus that significantly
      enhanced the reconstitution activity of the functional 30S subunit from
      unmodified 16S rRNA to approximately 57% of that from native-modified 16S rRNA.
      The effect of the mutation did not depend on the reconstitution scheme, anti-SD
      sequences, or the target genes to be translated. The mutation we found in this
      study enabled reconstitution of the active 30S subunit without rRNA modification,
      and thus would be a useful tool for simple construction of self-reproducing
      ribosomes.

PMID- 29053249
TI  - Holistic Lipidomics of the Human Gut Phenotype Using Validated Ultra-High
      Performance Liquid Chromatography Coupled to Hybrid Orbitrap Mass Spectrometry.
AB  - As lipids are assigned a plethora of biological functions, it is evident that
      dysregulated lipid metabolism signifies a key element in many pathological
      conditions. With this rationale, this study presents a validated lipidomics
      platform to map the fecal lipidome, which integrates unique information about
      host-gut microbiome interactions, gastrointestinal functionality, and dietary
      patterns. This particular method accomplished coverage across all eight lipid
      categories: fatty acyls, glycerolipids, phosphoglycerolipids, polyketides,
      prenols, saccharolipids, sphingolipids, and sterols. Generic extraction of freeze
      dried feces was achieved by solid-liquid extraction using methanol and methyl
      tert-butyl ether. Extracted components were separated by liquid chromatography,
      whereby the selected ethylene-bridged hybrid phenyl ultra-high-performance liquid
      chromatography stationary phase allowed fast separation of both individual lipid
      species and categories. Detection was achieved by high-resolution full-scan Q
      Exactive Orbitrap mass spectrometry and covered a broad m/z scan range (67-2300
      Da). Method validation was performed in a targeted fashion to evaluate the
      analytical performance across all lipid categories, revealing excellent linearity
      (R2 >= 0.9921), acceptable repeatability (coefficients of variance <=15.6%), and
      stable recovery (coefficients of variance <=11.9%). Method suitability for
      untargeted fingerprinting was verified, demonstrating adequate linearity (R2 >=
      0.90) for 75.3% and acceptable repeatability (coefficients of variance <=30%) for
      84.5% of about 9000 endogenous fecal compounds. Eventually, the potential of
      fecal lipidomics was exemplified within a clinical context of type 2 diabetes,
      thereby revealing significant perturbations [orthogonal partial least-squares
      discriminant analysis Q2(Y) of 0.728] in the fecal lipidome between participants
      with normal blood glucose levels (n = 26) and those with type 2 diabetes (n =
      17).

PMID- 29053250
TI  - Hierarchically-Designed 3D Flower-Like Composite Nanostructures as an
      Ultrastable, Reproducible, and Sensitive SERS Substrate.
AB  - Surface-enhanced Raman spectroscopy (SERS) is an attractive tool in the
      analytical sciences due to its high specificity and sensitivity. Because SERS
      active substrates are only available as two-dimensional arrays, the fabrication
      of three-dimensional (3D) nanostructures allows for an increased number of hot
      spots in the focus volume, thus further amplifying the SERS signal. Although a
      great number of fabrication strategies for powerful SERS substrates exist, the
      generation of 3D nanostructures with high complexity and periodicity is still
      challenging. For this purpose, we report an easy fabrication technique for 3D
      nanostructures following a bottom-up preparation protocol. Enzymatically
      generated silver nanoparticles (EGNPs) are prepared, and the growth of
      hierarchically-designed 3D flower-like silica-silver composite nanostructures is
      induced by applying plasma-enhanced atomic layer deposition (PE-ALD) on the
      EGNPs. The morphology of these nanocomposites can be varied by changes in the PE
      ALD cycle number, and a flower height of up to 10 MUm is found. Moreover, the
      metallized (e.g., silver or gold) 3D nanostructures resulting from 135 PE-ALD
      cycles of silica creation provide highly reproducible SERS signals across the
      hydrophobic surface. Within this contribution, the morphological studies, optical
      properties, as well as the SERS response of these metallized silica-silver
      composite nanostructures applying vitamin B2 as a model analyte are introduced.

PMID- 29053251
TI  - Electrochemiluminescent Pb2+-Driven Circular Etching Sensor Coupled to a DNA
      Micronet-Carrier.
AB  - Herein, an ultrasensitive electrochemiluminescent (ECL) strategy was designed
      based on the fabrication of a multi-interface DNA micronet-carrier via layer by
      layer hybridization of double-stranded DNAzyme-substrate to immobilize large
      amounts of ECL indicator, [Ru(dcbpy)2dppz]2+, in double-strand DNA on the
      electrode surface, generating enhanced ECL signals. When the double-stranded
      structures were cleaved circularly via Pb2+ in the detection sample, the ECL
      indicator was released, which resulted in a decreased ECL signal associated with
      the concentration of Pb2+, that had higher sensitivity and wider linear range. As
      a result, the developed ECL strategy exhibited a linear range from 50 pM to 500
      MUM with a detection limit of 4.73 pM, providing an alternative analytical
      strategy with excellent properties, including a high sensitivity and a wide
      linear range. Importantly, the ECL strategy could be readily expanded for various
      metal ions, proteins, nucleotide sequences, and cells, offering a simple and
      efficient technology for both environmentally safe assays and clinical
      diagnostics.

PMID- 29053252
TI  - Optogenetics Manipulation Enables Prevention of Biofilm Formation of Engineered
      Pseudomonas aeruginosa on Surfaces.
AB  - Synthetic biologists have attempted to solve real-world problems, such as those
      of bacterial biofilms, that are involved in the pathogenesis of many clinical
      infections and difficult to eliminate. To address this, we employed a blue light
      responding system and integrated it into the chromosomes of Pseudomonas
      aeruginosa. With making rational adaptions and improvements of the light
      activated system, we provided a robust and convenient means to spatiotemporally
      control gene expression and manipulate biological processes with minimal
      perturbation in P. aeruginosa. It increased the light-induced gene expression up
      to 20-fold. Moreover, we deliberately introduced a functional protein gene PA2133
      containing an EAL domain to degrade c-di-GMP into the modified system, and showed
      that the optimally engineered optogenetic tool inhibited the formation of P.
      aeruginosa biofilms through the induction of blue light, resulting in much
      sparser and thinner biofilms. Our approach establishes a methodology for
      leveraging the tools of synthetic biology to guide biofilm formation and engineer
      biofilm patterns with unprecedented spatiotemporal resolution. Furthermore, the
      findings suggest that the synthetic optogenetic system may provide a promising
      strategy that could be applied to control and fight biofilms.

PMID- 29053254
TI  - Versatile Tool for the Analysis of Metal-Protein Interactions Reveals the
      Promiscuity of Metallodrug-Protein Interactions.
AB  - Metallodrug-protein interactions contribute to their therapeutic effect (even
      when DNA is the dominant target), side-effects and are implicit in drug
      resistance. Here, we provide mass spectrometric-based evidence to show that
      metallodrug interactions with proteins are considerably more complex than current
      literature would suggest. Using native-like incubation and electrospray
      conditions together with an automated tool we designed for exhaustive mass
      spectra matching, the promiscuity of binding of cisplatin to ubiquitin is
      revealed, with 14 different binding sites observed. There is a binding preference
      to negatively charged sites on the protein, consistent with the cationic nature
      of the cisplatin adduct following aquation. These results have implications in
      metallodrug development and beyond to the toxicological effects of metal ions
      more generally.

PMID- 29053255
TI  - Fabrication of Nontoxic Reduced Graphene Oxide Protein Nanoframework as Sustained
      Antimicrobial Coating for Biomedical Application.
AB  - Bacterial colonization on medical devices is a major concern in the healthcare
      industry. In the present study, we report synthesis of environmental sustainable
      reduced graphene oxide (rGO) on the large scale through biosynthetic route and
      its potential application for antibacterial coating on medical devices. HRTEM
      image depicts formation of graphene nanosheet, while DLS and zeta potential
      studies reveal that in aqueous medium the average hydrodynamic size and surface
      charge of rGO are 4410 +/- 116 nm and -25.2 +/- 3.2 mV, respectively. The Raman,
      FTIR, and XPS data suggest in situ conjugation of protein with rGO. The as
      synthesized rGO protein nanoframework exhibits dose-dependent antibacterial
      activity and potential of killing of 94% of Escherichia coli when treated with 80
      MUg/mL of rGO for 4 h. The hemolytic and cytotoxicity studies demonstrate that
      rGO protein nanoframework is highly biocompatible at the same concentration
      showing significant antimicrobial properties. The rGO coated on the glass surface
      obtained through covalent bonding exhibits potent antibacterial activity.
      Antibacterial mechanism further demonstrates that rGO-protein nanoframework in
      dispersed state (rGO solution) exerts bactericidal effect through physical
      disruption accompanied by ROS-mediated biochemical responses. The rGO
      subsequently entering into the cytoplasm through the damaged membrane causes
      metabolic imbalance in the cells. In sharp contrast, physical damage of the cell
      membrane is the dominant antibacterial mechanism of rGO in the immobilized state
      (rGO coated glass). The obtained results help indepth understanding of the
      antibacterial mechanism of the biosynthesized rGO and a novel way to develop
      nontoxic antibacterial coating on medical devices to prevent bacterial infection.

PMID- 29053253
TI  - Surface Plasmon Resonance: Material and Interface Design for Universal
      Accessibility.

PMID- 29053256
TI  - Electrochemical Conversion of Fe3O4 Magnetic Nanoparticles to Electroactive
      Prussian Blue Analogues for Self-Sacrificial Label Biosensing of Avian Influenza
      Virus H5N1.
AB  - A serious impetus always exists to exploit new methods to enrich the prospect of
      nanomaterials. Here, we report electrochemical conversion (ECC) of magnetic
      nanoparticles (MNPs) to electroactive Prussian blue (PB) analogues accompanied by
      three interfacial effects and its exploitation for novel label self-sacrificial
      biosensing of avian influenza virus H5N1. The ECC method involves a high
      potential step to create strong acidic condition by splitting H2O to release Fe3+
      from the MNPs, and then a low-potential step leading to the reduction of
      coexisting K3Fe(CN)6 and Fe3+ to K4Fe(CN)6 and Fe2+, respectively, which react to
      form PB analogues. Unlike conventional solid/liquid electrochemical interfaces
      that need a supply of reactants by transportation from bulk solution and require
      additional template to generate porosity, the proposed method introduces MNPs on
      the electrode surface and makes them natural nanotemplates and nanoconfined
      sources of reactants. Therefore, the method presents interesting surface
      templating, generation-confinement, and refreshing effects/modes, which benefit
      the produced PB with higher porosity and electrochemical activity, and 3 orders
      of magnitude lower requirement for reactant concentration compared with
      conventional methods. Based on the ECC methods, a sandwich immunosensor is
      designed for rapid detection of avian influenza virus H5N1 using MNPs as self
      sacrificial labels to produce PB for signal amplification. Taking full advantages
      of the high abundance of Fe in MNPs and three surface effects, the ECC method
      endows the biosensing technology with high sensitivity and a limit of detection
      down to 0.0022 hemagglutination units, which is better than those of most
      reported analogues. The ECC method may lead to a new direction for application of
      nanomaterials and new electrochemistry modes.

PMID- 29053257
TI  - Orthogonal Screening of Anticancer Drugs Using an Open-Access Microfluidic Tissue
      Array System.
AB  - Screening for potential drug combinations presents significant challenges to the
      current microfluidic cell culture systems, due to the requirement of flexibility
      in liquid handling. To overcome this limitation, we present here an open-access
      microfluidic tissue array system specifically designed for drug combination
      screening. The microfluidic chip features a key structure in which a nanoporous
      membrane is sandwiched by a cell culture chamber array layer and a corresponding
      media reservoir array layer. The microfluidic approach takes advantage of the
      characteristics of the nanoporous membrane: on one side, this membrane permits
      the flow of air but not liquid, thus acting as a flow-stop valve to enable
      automatic cell distribution; on the other side, it allows diffusion-based media
      exchange and thus mimics the endothelial layer. In synergy with a liquid
      transferring platform, the open-access microfluidic system enables complex
      multistep operations involving long-term cell culture, medium exchange, multistep
      drug treatment, and cell-viability testing. By using the microfluidic protocol, a
      10 * 10 tissue array was constructed in 90 s, followed by schedule-dependent drug
      testing. Morphological and immunohistochemical assays indicated that the
      resultant tumor tissue was faithful to that in vivo. Drug-testing assays showed
      that the incorporation of the nanoporous membrane further decreased killing
      efficacy of the anticancer agents, indicating its function as an endothelial
      layer. Robustness of the microfluidic system was demonstrated by implementing a
      three-factor, three-level orthogonal screening of anticancer drug combinations,
      with which 67% of the testing (9 vs. 27) was saved. Experimental results
      demonstrated that the microfluidic tissue system presented herein is flexible and
      easy-to-use, thus providing an ideal tool for performing complex multistep cell
      assays with high efficiencies.

PMID- 29053258
TI  - Parrotfish Teeth: Stiff Biominerals Whose Microstructure Makes Them Tough and
      Abrasion-Resistant To Bite Stony Corals.
AB  - Parrotfish (Scaridae) feed by biting stony corals. To investigate how their teeth
      endure the associated contact stresses, we examine the chemical composition, nano
      and microscale structure, and the mechanical properties of the steephead
      parrotfish Chlorurus microrhinos tooth. Its enameloid is a fluorapatite
      (Ca5(PO4)3F) biomineral with outstanding mechanical characteristics: the mean
      elastic modulus is 124 GPa, and the mean hardness near the biting surface is 7.3
      GPa, making this one of the stiffest and hardest biominerals measured; the mean
      indentation yield strength is above 6 GPa, and the mean fracture toughness is
      ~2.5 MPa.m1/2, relatively high for a highly mineralized material. This
      combination of properties results in high abrasion resistance. Fluorapatite X-ray
      absorption spectroscopy exhibits linear dichroism at the Ca L-edge, an effect
      that makes peak intensities vary with crystal orientation, under linearly
      polarized X-ray illumination. This observation enables polarization-dependent
      imaging contrast mapping of apatite, a method to quantitatively measure and
      display nanocrystal orientations in large, pristine arrays of nano- and
      microcrystalline structures. Parrotfish enameloid consists of 100 nm-wide,
      microns long crystals co-oriented and assembled into bundles interwoven as the
      warp and the weave in fabric and therefore termed fibers here. These fibers
      gradually decrease in average diameter from 5 MUm at the back to 2 MUm at the tip
      of the tooth. Intriguingly, this size decrease is spatially correlated with an
      increase in hardness.

PMID- 29053259
TI  - Muconic Acid Production via Alternative Pathways and a Synthetic "Metabolic
      Funnel".
AB  - Muconic acid is a promising platform biochemical and precursor to adipic acid,
      which can be used to synthesize various plastics and polymers. In this study, the
      systematic construction and comparative evaluation of a modular network of non
      natural pathways for muconic acid biosynthesis was investigated in Escherichia
      coli, including via three distinct and novel pathways proceeding via phenol as a
      common intermediate. However, poor recombinant activity and high promiscuity of
      phenol hydroxylase ultimately limited "phenol-dependent" muconic acid production.
      A fourth pathway proceeding via p-hydroxybenzoate, protocatechuate, and catechol
      was accordingly developed, though with muconic acid titers by this route reaching
      just 819 mg/L, its performance lagged behind that of the established, "3
      dehydroshikimiate-derived" route. Finally, these two most promising pathways were
      coexpressed in parallel to create a synthetic "metabolic funnel" that, by
      enabling maximal net precursor assimilation and flux while preserving native
      chorismate biosynthesis, nearly doubled muconic acid production to up to >3.1 g/L
      at a glucose yield of 158 mg/g while introducing only a single auxotrophy. This
      generalizable, "funneling" strategy is expected to have broad applications in
      metabolic engineering for further enhancing production of muconic acid, as well
      as other important bioproducts of interest.

PMID- 29053260
TI  - QM/MM Study of the Nitrogenase MoFe Protein Resting State: Broken-Symmetry
      States, Protonation States, and QM Region Convergence in the FeMoco Active Site.
AB  - Nitrogenase is one of the most fascinating enzymes in nature, being responsible
      for all biological nitrogen reduction. Despite decades of research, it is among
      the enzymes in bioinorganic chemistry whose mechanism is the most poorly
      understood. The MoFe protein of nitrogenase contains an iron-molybdenum-sulfur
      cluster, FeMoco, where N2 reduction takes place. The resting state of FeMoco has
      been characterized by crystallography, multiple spectroscopic techniques, and
      theory (broken-symmetry density functional theory), and all heavy atoms are now
      characterized. The cofactor charge, however, has been controversial, the
      electronic structure has proved enigmatic, and little is known about the
      mechanism. While many computational studies have been performed on FeMoco, few
      have taken the protein environment properly into account. In this study, we put
      forward QM/MM models of the MoFe protein from Azotobacter vinelandii, centered on
      FeMoco. By a detailed analysis of the FeMoco geometry and comparison to the
      atomic resolution crystal structure, we conclude that only the [MoFe7S9C]1-
      charge is a possible resting state charge. Further, we find that of the three
      lowest energy broken-symmetry solutions of FeMoco, the BS7-235 spin isomer (where
      235 refers to Fe atoms that are "spin-down") is the only one that can be
      reconciled with experiment. This is revealed by a comparison of the metal-metal
      distances in the experimental crystal structure, a rare case of spin-coupling
      phenomena being visible through the molecular structure. This could be
      interpreted as the enzyme deliberately stabilizing a specific electronic state of
      the cofactor, possibly for tuning specific reactivity on specific metal atoms.
      Finally, we show that the alkoxide group on the Mo-bound homocitrate must be
      protonated under resting state conditions, the presence of which has implications
      regarding the nature of FeMoco redox states as well as for potential substrate
      reduction mechanisms.

PMID- 29053261
TI  - Influence of Scale on Biomass Growth and Nutrient Removal in an Algal-Bacterial
      Leachate Treatment System.
AB  - Data collected from experiments conducted at a flask scale are regularly used as
      input data for life cycle assessments and techno-economic analyses for predicting
      the potential productivities of large-scale commercial facilities. This study
      measures and compares nitrogen removal and biomass growth rates in treatment
      systems that utilize an algae-bacteria consortium to remediate landfill leachate
      at three scales: small (0.25 L), medium (100 L), and large (1000 L). The medium-
      and large-scale vessels were run for 52 consecutive weeks as semibatch reactors
      under variable environmental conditions. The small-scale experiments were
      conducted in flasks as batch experiments under controlled environmental
      conditions. Kolomogov-Smirnov statistical tests, which compare the distributions
      of entire data sets, were used to determine if the ammonia removal, total
      nitrogen removal, and biomass growth rates at each scale were statistically
      different. Results from the Kolmogov-Smirnov comparison indicate that there is a
      significant difference between all rates determined in the large-scale vessels
      compared to those in the small-scale vessels. These results suggest that small
      scale experiments may not be appropriate as input data in predictive analyses of
      full scale algal processes. The accumulation of nitrite and nitrate within the
      reactor, observed midway through the experimental process, is attributed to high
      relative abundances of ammonia- and nitrite-oxidizing bacteria, identified via
      metagenomic analysis.

PMID- 29053262
TI  - Carotenoid Singlet Fission Reactions in Bacterial Light Harvesting Complexes As
      Revealed by Triplet Excitation Profiles.
AB  - Carotenoids (Cars) in bacterial photosynthesis are known as accessory light
      harvesters and photoprotectors. Recently, the singlet fission (SF) reaction
      initiated by Car photoabsorption has been recognized to be an effective
      excitation deactivation channel disfavoring the light harvesting function. Since
      the SF reaction and the triplet sensitization reaction underlying photoprotection
      both yield triplet excited state Cars (3Car*), their contribution to the overall
      3Car* photoproduction are difficult to disentangle. To tackle this problem, we
      resorted to the triplet excitation profiles (TEPs), i.e., the actinic spectra of
      the overall 3Car* photoproduction. The TEPs combined with the conventional
      fluorescence excitation spectra allowed us to extract the neat SF contribution,
      which can serve as a spectroscopic measure for the SF reactivity. This novel
      spectroscopic strategy was applied to analyze the light harvesting complexes
      (LHs) from Tch. tepidum and Rba. sphaeroides 2.4.1. The results unambiguously
      showed that the SF reaction of Cars proceeds with an intramolecular scheme, even
      in the case of LH1-RC from Rba. sphaeroides 2.4.1 likely binding a secondary pool
      of Cars. Regarding the SF-reactivity, the geometric distortion in the conjugated
      backbone of Cars was shown to be the structural determinant, while the length of
      the Car conjugation was suggested to be relevant to the effective localization of
      the geminate triplets to avoid being annihilated. The SF reaction scheme and
      structure-activity relationship revealed herein will be useful not only in
      deepening our understanding of the roles of Cars in photosynthesis, but also in
      enlightening the applications of Cars in artificial light conversion systems.

PMID- 29053263
TI  - Asymmetric Darzens Reaction of Isatins with Diazoacetamides Catalyzed by Chiral
      BINOL-Titanium Complex.
AB  - An efficient catalytic asymmetric Darzens reaction of N-protected isatins with
      diazoacetamides using a chiral BINOL/Ti(OiPr)4 complex as the catalyst has been
      developed. This reaction is a straightforward method for the synthesis of spiro
      epoxyoxindoles in 40-95% yields, up to >20:1 dr and up to >99% ee. A gram-scale
      reaction was also achieved in 95% yield with excellent stereoselectivity and
      enantioselectivity (>20:1 dr, >99% ee).

PMID- 29053264
TI  - Cytotoxic Half-Sandwich Rh(III) and Ir(III) beta-Diketonates.
AB  - A series of half-sandwich pentamethylcyclopentadienyl rhodium(III) and
      iridium(III) complexes [Cp*M(DBM/HDB/AVB)Cl] and
      [Cp*M(DBM/HDB/AVB)(PTA)][SO3CF3], where Cp* = pentamethylcyclopentadienyl, the
      proligands DBMH = dibenzoylmethane, HDBH = o-hydroxydibenzoylmethane, AVBH =
      avobenzone, and PTA = 1,3,5-triaza-7-phosphaadamantane, is reported. All the
      complexes were characterized by IR, 1H and 13C NMR spectroscopy, electrospray
      ionization mass spectrometry, elemental analysis, and DFT calculations. Five of
      the complexes have also been characterized in the solid-state by X-ray
      crystallography. The cytotoxicity of the complexes has been evaluated against
      human ovarian A2780 and A2780cisR cell lines and, with the only exception of
      complexes 1 and 2 that display a negligible cytotoxicity, exhibit moderate
      cytotoxicity toward both cancer cell lines. However, the complexes do not show
      cancer cell selectivity with respect to human embryonic kidney HEK293 cells.

PMID- 29053265
TI  - Step-Economical Photoassisted Diversity-Oriented Synthesis: Sustaining Cascade
      Photoreactions in Oxalyl Anilides to Access Complex Polyheterocyclic Molecular
      Architectures.
AB  - Atom- and step-economy in photoassisted diversity-oriented synthesis (DOS) is
      achieved with a versatile oxalyl linker offering rapid access to complex alkaloid
      mimics in very few experimentally simple steps: (i) it allows for fast tethering
      of the photoactive core to the unsaturated pendants, especially important in the
      case of (hetero)aromatic amines-essentially a one-pot reaction with no isolation
      of intermediates; (ii) the alpha-dicarbonyl tether acts as a chromophore
      enhancer, extending the conjugation chain and facilitating the "harvest" of the
      lower energy photons for the primary and secondary photoreactions; (iii) it
      enhances the quantum yield of intersystem crossing (ISC), i.e., it is capable of
      sensitizing secondary photochemical processes in the cascade; and (iv) the tether
      forms an additional heterocyclic moiety, imidazolidine-4,5-dione, a known
      pharmacophore. The overall photoassisted cascade is an efficient complexity
      building process as quantified by computed step-normalized complexity indices,
      leading to extended polyheterocyclic molecular architectures comparable in
      complexity to natural products such as paclitaxel while requiring only 2-4 simple
      synthetic steps from readily available chemical feedstock.

PMID- 29053266
TI  - Structure-Activity Relationships of New Natural Product-Based Diaryloxazoles with
      Selective Activity against Androgen Receptor-Positive Breast Cancer Cells.
AB  - Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved
      patient survival, but there are no therapies for triple negative breast cancers
      (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or
      amplification or overexpression of HER2. Gene expression profiling of TNBC has
      identified molecular subtypes and representative cell lines. An extract of the
      Texas native plant Amyris texana was found to have selective activity against MDA
      MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC.
      Bioassay-guided fractionation identified two oxazole natural products with
      selective activity against this cell line. Conducted analog synthesis and
      structure-activity relationship studies provided analogs with more potent and
      selective activity against two LAR subtype cell line models, culminating in the
      discovery of compound 30 (CIDD-0067106). Lead compounds discovered have potent
      and selective antiproliferative activities, and mechanisms of action studies show
      they inhibit the activity of the mTORC1 pathway.

PMID- 29053267
TI  - Uptake Kinetics and Trophic Transfer of Tungsten from Cabbage to a Herbivorous
      Animal Model.
AB  - This investigation builds on previous studies on military-relevant tungsten (W)
      to more thoroughly explore environmental pathways and bioaccumulation kinetics
      during direct soil exposure versus trophic transfer and elucidate its relative
      accumulation and speciation in different snail organs. The modeled steady-state
      concentration and bioaccumulation factor (BAF) of W from soil into cabbage were
      302 mg/kg and 0.55, respectively. Steady-state concentrations (34 mg/kg) and BAF
      values (0.05) obtained for the snail directly exposed to contaminated soil were
      lower than trophic transfer by consumption of W-contaminated cabbage (tissue
      concentration of 86 mg/kg; BAF of 0.36). Thus, consumption of contaminated food
      is the most important pathway for W mobility in this food chain. The highest
      concentrations of W compartmentalization were in the snail's hepatopancreas based
      on wet chemistry and synchrotron-based investigations. Chemical speciation via
      inductively couple plasma mass spectrometry showed a higher degree of
      polytungstate partitioning in the hepatopancreas relative to the rest of the
      body. Based on synchrotron analysis, W was incorporated into the shell matrix
      during exposure, particularly during the regeneration of damaged shell. This
      offers the potential for application of the shell as a longer-term biomonitoring
      and forensics tool for historic exposure.

PMID- 29053268
TI  - Synthesis, Pharmacology, and Molecular Docking Studies on 6-Desoxo-N
      methylmorphinans as Potent MU-Opioid Receptor Agonists.
AB  - Position 6 of the morphinan skeleton plays a key role in the MU-opioid receptor
      (MOR) activity in vitro and in vivo. We describe the consequence of the 6
      carbonyl group deletion in N-methylmorphinan-6-ones 1-4 on ligand-MOR
      interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and
      4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy
      substituted 3a displays significantly increased MOR binding and agonist potency
      and a distinct binding mode compared with its analogue 3.

PMID- 29053269
TI  - Thermally Activated Delayed Fluorescence from Ag(I) Complexes: A Route to 100%
      Quantum Yield at Unprecedentedly Short Decay Time.
AB  - The four new Ag(I) complexes Ag(phen)(P2-nCB) (1), Ag(idmp)(P2-nCB) (2),
      Ag(dmp)(P2-nCB) (3), and Ag(dbp)(P2-nCB) (4) with P2-nCB = bis(diphenylphosphine)
      nido-carborane, phen = 1,10-phenanthroline, idmp = 4,7-dimethyl-1,10
      phenanthroline, dmp = 2,9-dimethyl-1,10-phenanthroline, and dbp = 2,9-di-n-butyl
      1,10-phenanthroline were designed to demonstrate how to develop Ag(I) complexes
      that exhibit highly efficient thermally activated delayed fluorescence (TADF).
      The substituents on the 1,10-phenanthroline ligand affect the photophysical
      properties strongly (i) electronically via influencing the radiative rate of the
      S1 -> S0 transition and (ii) structurally by rigidifying the molecular geometry
      with respect to geometry changes occurring in the lowest excited S1 and T1
      states. The oscillator strength of the S1 <-> S0 transition f(S1 <-> S0)-an
      important parameter for the TADF efficiency being proportional to the radiative
      rate-can be increased from f(S1 <-> S0) = 0.0258 for Ag(phen)(P2-nCB) (1) to f(S1
      <-> S0) = 0.0536 for Ag(dbp)(P2-nCB) (4), as calculated for the T1 state
      optimized geometries. This parameter governs the radiative TADF decay time (taur)
      at ambient temperature, found to be taur = 5.6 MUs for Ag(phen)(P2-nCB) (1) but
      only taur = 1.4 MUs for Ag(dbp)(P2-nCB) (4)-a record TADF value. In parallel, the
      photoluminescence quantum yield (PhiPL) measured for powder samples at ambient
      temperature is boosted up from PhiPL = 36% for Ag(phen)(P2-nCB) (1) to PhiPL =
      100% for Ag(dbp)(P2-nCB) (4). This is a consequence of a cooperative effect of
      both decreasing the nonradiative decay rate and increasing the radiative decay
      rate in the series from Ag(phen)(P2-nCB) (1), Ag(idmp)(P2-nCB) (2), and
      Ag(dmp)(P2-nCB) (3) to Ag(dbp)(P2-nCB) (4). Another parameter important for the
      TADF behavior is the activation energy of the S1 state from the state T1,
      DeltaE(S1-T1). Experimentally it is determined for the complexes Ag(dmp)(P2-nCB)
      (3) and Ag(dbp)(P2-nCB) (4) to be of moderate size of DeltaE(S1-T1) = 650 cm-1.

PMID- 29053270
TI  - Computation of Ground-State Properties in Molecular Systems: Back-Propagation
      with Auxiliary-Field Quantum Monte Carlo.
AB  - We address the computation of ground-state properties of chemical systems and
      realistic materials within the auxiliary-field quantum Monte Carlo method. The
      phase constraint to control the Fermion phase problem requires the random walks
      in Slater determinant space to be open-ended with branching. This in turn makes
      it necessary to use back-propagation (BP) to compute averages and correlation
      functions of operators that do not commute with the Hamiltonian. Several BP
      schemes are investigated, and their optimization with respect to the phaseless
      constraint is considered. We propose a modified BP method for the computation of
      observables in electronic systems, discuss its numerical stability and
      computational complexity, and assess its performance by computing ground-state
      properties in several molecular systems, including small organic molecules.

PMID- 29053271
TI  - Discovery of 7-[18F]Fluorotryptophan as a Novel Positron Emission Tomography
      (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo.
AB  - Tryptophan and its metabolites are involved in different physiological and
      pathophysiological processes. Consequently, positron emission tomography (PET)
      tracers addressing tryptophan metabolic pathways should allow the detection of
      different pathologies like neurological disorders and cancer. Herein we report an
      efficient method for the preparation of fluorotryptophans labeled in different
      positions with 18F and their biological evaluation. 4-7-[18F]Fluorotryptophans
      ([18F]FTrps) were prepared according to a modified protocol of alcohol-enhanced
      Cu-mediated radiofluorination in 30-53% radiochemical yields. In vitro
      experiments demonstrated high cellular uptake of 4-7-[18F]FTrps in different
      tumor cell lines. 4, 5-, and 6-[18F]FTrps, although stable in vitro, suffered
      from rapid in vivo defluorination. In contrast, 7-[18F]FTrp demonstrated a high
      in vivo stability and enabled a clear delineation of serotonergic areas and
      melatonin-producing pineal gland in rat brains. Moreover 7-[18F]FTrp accumulated
      in different tumor xenografts in a chick embryo CAM model. Thus, 7-[18F]FTrp
      represents a highly promising PET probe for imaging of Trp metabolism.

PMID- 29053272
TI  - Cardiotoxins: Functional Role of Local Conformational Changes.
AB  - Cardiotoxins (CTs) from snake venoms are a family of homologous highly basic
      proteins that have extended hydrophobic patterns on their molecular surfaces. CTs
      are folded into three beta-structured loops stabilized by four disulfide bridges.
      Being well-structured in aqueous solution, most of these proteins are membrane
      active, although the exact molecular mechanisms of CT-induced cell damage are
      still poorly understood. To elucidate the structure-function relationships in
      CTs, a detailed knowledge of their spatial organization and local conformational
      dynamics is required. Protein domain motions can be either derived from a set of
      experimental structures or generated via molecular dynamics (MD). At the same
      time, traditional clustering algorithms in the Cartesian coordinate space often
      fail to properly take into account the local large-scale dihedral angle
      transitions that occur in MD simulations. This is because such perturbations are
      usually offset by changes in the neighboring dihedrals, thus preserving the
      overall protein fold. States with a "locally perturbed" backbone were found in
      experimental 3D models of some globular proteins and have been shown to be
      functionally meaningful. In this work, the possibility of large-scale dihedral
      angle transitions in the course of long-term MD in explicit water was explored
      for three CTs with different membrane activities: CT 1, 2 (Naja oxiana) and CT A3
      (Naja atra). Analysis of the MD-derived distributions of backbone torsion angles
      revealed several important common and specific features in the structural/dynamic
      behavior of these proteins. First, large-amplitude transitions were detected in
      some residues located in the functionally important loop I region. The K5/L6 pair
      of residues was found to induce a perturbation of the hydrophobic patterns on the
      molecular surface of CTs-reversible breaking of a large nonpolar zone ("bottom")
      into two smaller ones and their subsequent association. Second, the
      characteristic sizes of these patterns perfectly coincided with the dimensions of
      the nonpolar zones on the surfaces of model two-component (zwitterionic/anionic)
      membranes. Taken together with experimental data on the CT-induced leakage of
      fluorescent dye from such membranes, these results allowed us to formulate a two
      stage mechanism of CT-membrane binding. The principal finding of this study is
      that even local conformational dynamics of CTs can seriously affect their
      functional activity via a tuning of the membrane binding site - specific "hot
      spots" (like the K5/L6 pair) in the protein structure.

PMID- 29053274
TI  - From Racemic Metal Nanoparticles to Optically Pure Enantiomers in One Pot.
AB  - A general strategy, using mixed ligands, is utilized to synthesize atomically
      precise, intrinsically chiral nanocluster [Ag78(DPPP)6(SR)42] (Ag78) where DPPP
      is the achiral 1,3-bis(diphenyphosphino)propane and SR = SPhCF3. Ag78
      crystallizes as racemates in a centric space group. Using chiral diphosphines
      BDPP = 2,4-bis(diphenylphosphino)pentane, the enantiomeric pair [Ag78(R/S
      BDPP)6(SR)42] can be prepared with 100% optical purity. The chiral diphosphines
      gives rise to, separately, two asymmetric surface coordination motifs composed of
      tetrahedral R3PAg(SR)3 moieties. The flexible nature of C-C-C angles between the
      two phosphorus atoms restricts the relative orientation of the tetrahedral
      R3PAg(SR)3 moieties, thereby resulting in the enantiomeric selection of the
      intrinsic chiral metal core. This proof-of-concept strategy raises the prospect
      of enantioselectively synthesizing optically pure, atomically precise chiral
      noble metal nanoclusters for specific applications.

PMID- 29053273
TI  - Distinguishing Nitro vs Nitrito Coordination in Cytochrome c' Using Vibrational
      Spectroscopy and Density Functional Theory.
AB  - Nitrite coordination to heme cofactors is a key step in the anaerobic production
      of the signaling molecule nitric oxide (NO). An ambidentate ligand, nitrite has
      the potential to coordinate via the N- (nitro) or O- (nitrito) atoms in a manner
      that can direct its reactivity. Distinguishing nitro vs nitrito coordination,
      along with the influence of the surrounding protein, is therefore of particular
      interest. In this study, we probed Fe(III) heme-nitrite coordination in
      Alcaligenes xylosoxidans cytochrome c' (AXCP), an NO carrier that excludes anions
      in its native state but that readily binds nitrite (Kd ~ 0.5 mM) following a
      distal Leu16 -> Gly mutation to remove distal steric constraints. Room
      temperature resonance Raman spectra (407 nm excitation) identify nu(Fe-NO2),
      delta(ONO), and nus(NO2) nitrite ligand vibrations in solution. Illumination with
      351 nm UV light results in photoconversion to {FeNO}6 and {FeNO}7 states,
      enabling FTIR measurements to distinguish nus(NO2) and nuas(NO2) vibrations from
      differential spectra. Density functional theory calculations highlight the
      connections between heme environment, nitrite coordination mode, and vibrational
      properties and confirm that nitrite binds to L16G AXCP exclusively through the N
      atom. Efforts to obtain the nitrite complex crystal structure were hampered by
      photochemistry in the X-ray beam. Although low dose crystal structures could be
      modeled with a mixed nitrite (nitro)/H2O distal population, their
      photosensitivity and partial occupancy underscores the value of the vibrational
      approach. Overall, this study sheds light on steric determinants of heme-nitrite
      binding and provides vibrational benchmarks for future studies of heme protein
      nitrite reactions.

PMID- 29053275
TI  - Thiazolino 2-Pyridone Amide Isosteres As Inhibitors of Chlamydia trachomatis
      Infectivity.
AB  - Chlamydia trachomatis is a global health burden due to its prevalence as a
      sexually transmitted disease and as the causative agent of the eye infection
      trachoma. We recently discovered 3-amido thiazolino 2-pyridones which attenuated
      C. trachomatis infectivity without affecting host cell or commensal bacteria
      viability. We present here the synthesis and evaluation of nonhydrolyzable amide
      isosteres based on this class, leading to highly potent 1,2,3-triazole based
      infectivity inhibitors (EC50 <= 20 nM).

PMID- 29053276
TI  - Atomic-Scale Front Propagation at the Onset of Frictional Sliding.
AB  - Macroscopic frictional sliding emerges from atomic-scale interactions and
      processes at the contact interface, but bridging the gap between micro and macro
      scales still remains an unsolved challenge. Direct imaging of the contact surface
      and simultaneous measurement of stress fields during macroscopic frictional slip
      revealed the formation of crack precursors, questioning the traditional picture
      of frictional contacts described in terms of a single degree of freedom. Here we
      study the onset of frictional slip on the atomic scale by simulating the motion
      of an aluminum block pushed by a slider on a copper substrate. We show the
      formation of dynamic slip front propagation and precursory activity that resemble
      macroscopic observations. The analysis of stress patterns during slip, however,
      reveals subtle effects due to the lattice structures that hinder a direct
      application of linear elastic fracture mechanics. Our results illustrate that
      dynamic front propagation arises already on the atomic scales and shed light on
      the connections between atomic-scale and macroscopic friction.

PMID- 29053278
TI  - It Is Complicated: Curvature, Diffusion, and Lipid Sorting within the Two
      Membranes of Escherichia coli.
AB  - The cell envelope of Gram-negative bacteria is composed of two membranes
      separated by a soluble region. Here, we report microsecond time scale coarse
      grained molecular dynamics simulations of models of the Escherichia coli cell
      envelope that incorporate both membranes and various native membrane proteins.
      Our results predict that both the inner and outer membranes curve in a manner
      dependent on the size of the embedded proteins. The tightly cross-linked
      lipopolysaccharide molecules (LPS) of the outer membrane cause a strong coupling
      between the movement of proteins and lipids. While the flow of phospholipids is
      more random, their diffusion is nevertheless influenced by nearby proteins. Our
      results reveal protein-induced lipid sorting, whereby cardiolipin is
      significantly enriched within the vicinity of the water channel AqpZ and the
      multidrug efflux pump AcrBZ. In summary, our results provide unprecedented
      details of the intricate relationship between both membranes of E. coli and the
      proteins embedded within them.

PMID- 29053277
TI  - Utilizing Inverse Emulsion Polymerization To Generate Responsive Nanogels for
      Cytosolic Protein Delivery.
AB  - Therapeutic biologics have various advantages over synthetic drugs in terms of
      selectivity, their catalytic nature, and, thus, therapeutic efficacy. These
      properties offer the potential for more effective treatments that may also
      overcome the undesirable side effects observed due to off-target toxicities of
      small molecule drugs. Unfortunately, systemic administration of biologics is
      challenging due to cellular penetration, renal clearance, and enzymatic
      degradation difficulties. A delivery vehicle that can overcome these challenges
      and deliver biologics to specific cellular populations has the potential for
      significant therapeutic impact. In this work, we describe a redox-responsive
      nanoparticle platform, which can encapsulate hydrophilic proteins and release
      them only in the presence of a reducing stimulus. We have formulated these
      nanoparticles using an inverse emulsion polymerization (IEP) methodology,
      yielding inverse nanoemulsions, or nanogels. We have demonstrated our ability to
      overcome the liabilities that contribute to activity loss by delivering a highly
      challenging cargo, functionally active caspase-3, a cysteine protease susceptible
      to oxidative and self-proteolytic insults, to the cytosol of HeLa cells by
      encapsulation inside a redox-responsive nanogel.

PMID- 29053279
TI  - Reduced Graphene Oxide/LiI Composite Lithium Ion Battery Cathodes.
AB  - Li-iodine chemistry is of interest for electrochemical energy storage because it
      has been shown to provide both high power and high energy density. However, Li
      iodine batteries are typically formed using Li metal and elemental iodine, which
      presents safety and fabrication challenges (e.g., the high vapor pressure of
      iodine). These disadvantages could be circumvented by using LiI as a starting
      cathode. Here, we present fabrication of a reduced graphene oxide (rGO)/LiI
      composite cathode, enabling for the first time the use of LiI as the Li-ion
      battery cathode. LiI was coated on rGO by infiltration of an ethanolic solution
      of LiI into a compressed rGO aerogel followed by drying. The free-standing
      rGO/LiI electrodes show stable long-term cycling and good rate performance with
      high specific capacity (200 mAh g-1 at 0.5 C after 100 cycles) and small
      hysteresis (0.056 V at 1 C). Shuttling was suppressed significantly. We speculate
      the improved electrochemical performance is due to strong interactions between
      the active materials and rGO, and the reduced ion and electron transport
      distances provided by the three-dimensional structured cathode.

PMID- 29053281
TI  - Insights into Water-Induced Phase Separation in Itraconazole-Hydroxypropylmethyl
      Cellulose Spin Coated and Spray Dried Dispersions.
AB  - For amorphous solid dispersions, understanding the phase behavior of a given drug
      polymer blend and factors that influence miscibility is crucial to designing an
      optimally performing formulation. However, it can be challenging to fully map the
      phase behavior of some systems, especially those produced using a cosolvent
      system. In this study, a comprehensive investigation of phase separation in
      itraconazole-hydroxypropylmethylcellulose (ITZ-HPMC) blends fabricated using
      solvent evaporation processes, including spin coating and spray drying, has been
      carried out. Phase separation was found to be driven by the presence of water,
      either acquired from the environment or from the solvent system. ITZ nanospecies
      were observed during the solvent evaporation process prior to solidification. The
      use of high resolution imaging techniques such as transmission electron
      microscopy including bright field and high angle annular dark field imaging,
      enabled detailed characterization of the microstructure of phase separated
      systems. Spectroscopic investigations suggested that drug domains contain
      supramolecular drug aggregates in which the nematic assembly of ITZ molecules
      results in the coupling of the optical transitions of ITZ monomers. Importantly,
      a similar pattern of behavior between drug-polymer phase in spin coated and spray
      dried dispersions was observed. The presence of as little as 1% water in the
      solvent was found to induce phase separation in the spray dried particles, which
      was detected using the unique photophysical properties of ITZ and fluorescence
      spectroscopy. The study highlights the complexity of drug-polymer phase behavior
      and the influence of solvent properties.

PMID- 29053280
TI  - Structural and Biochemical Investigation of PglF from Campylobacter jejuni
      Reveals a New Mechanism for a Member of the Short Chain Dehydrogenase/Reductase
      Superfamily.
AB  - Within recent years it has become apparent that protein glycosylation is not
      limited to eukaryotes. Indeed, in Campylobacter jejuni, a Gram-negative
      bacterium, more than 60 of its proteins are known to be glycosylated. One of the
      sugars found in such glycosylated proteins is 2,4-diacetamido-2,4,6-trideoxy
      alpha-d-glucopyranose, hereafter referred to as QuiNAc4NAc. The pathway for its
      biosynthesis, initiating with UDP-GlcNAc, requires three enzymes referred to as
      PglF, PglE, and PlgD. The focus of this investigation is on PglF, an NAD+
      dependent sugar 4,6-dehydratase known to belong to the short chain
      dehydrogenase/reductase (SDR) superfamily. Specifically, PglF catalyzes the first
      step in the pathway, namely, the dehydration of UDP-GlcNAc to UDP-2-acetamido-2,6
      dideoxy-alpha-d-xylo-hexos-4-ulose. Most members of the SDR superfamily contain a
      characteristic signature sequence of YXXXK where the conserved tyrosine functions
      as a catalytic acid or a base. Strikingly, in PglF, this residue is a methionine.
      Here we describe a detailed structural and functional investigation of PglF from
      C. jejuni. For this investigation five X-ray structures were determined to
      resolutions of 2.0 A or better. In addition, kinetic analyses of the wild-type
      and site-directed variants were performed. On the basis of the data reported
      herein, a new catalytic mechanism for a SDR superfamily member is proposed that
      does not require the typically conserved tyrosine residue.

PMID- 29053282
TI  - R-Axion at Colliders.
AB  - We study the effective theory of a generic class of hidden sectors where
      supersymmetry is broken together with an approximate R-symmetry at low energy.
      The light spectrum contains the gravitino and the pseudo-Nambu-Goldstone boson of
      the R-symmetry, the R-axion. We derive new model-independent constraints on the R
      axion decay constant for R-axion masses ranging from GeV to TeV, which are of
      relevance for hadron colliders, lepton colliders, and B factories. The current
      bounds allow for the exciting possibility that the first sign of supersymmetry
      will be the R-axion. We point out its most distinctive signals, providing a new
      experimental handle on the properties of the hidden sector and a solid motivation
      for searches of axionlike particles.

PMID- 29053283
TI  - Localization Transition Induced by Learning in Random Searches.
AB  - We solve an adaptive search model where a random walker or Levy flight
      stochastically resets to previously visited sites on a d-dimensional lattice
      containing one trapping site. Because of reinforcement, a phase transition occurs
      when the resetting rate crosses a threshold above which nondiffusive stationary
      states emerge, localized around the inhomogeneity. The threshold depends on the
      trapping strength and on the walker's return probability in the memoryless case.
      The transition belongs to the same class as the self-consistent theory of
      Anderson localization. These results show that similarly to many living organisms
      and unlike the well-studied Markovian walks, non-Markov movement processes can
      allow agents to learn about their environment and promise to bring adaptive
      solutions in search tasks.

PMID- 29053284
TI  - Structure of the Resource Theory of Quantum Coherence.
AB  - Quantum coherence is an essential feature of quantum mechanics which is
      responsible for the departure between the classical and quantum world. The
      recently established resource theory of quantum coherence studies possible
      quantum technological applications of quantum coherence, and limitations that
      arise if one is lacking the ability to establish superpositions. An important
      open problem in this context is a simple characterization for incoherent
      operations, constituted by all possible transformations allowed within the
      resource theory of coherence. In this Letter, we contribute to such a
      characterization by proving several upper bounds on the maximum number of
      incoherent Kraus operators in a general incoherent operation. For a single qubit,
      we show that the number of incoherent Kraus operators is not more than 5, and it
      remains an open question if this number can be reduced to 4. The presented
      results are also relevant for quantum thermodynamics, as we demonstrate by
      introducing the class of Gibbs-preserving strictly incoherent operations, and
      solving the corresponding mixed-state conversion problem for a single qubit.

PMID- 29053285
TI  - Upper Bound on Diffusivity.
AB  - The linear growth of operators in local quantum systems leads to an effective
      light cone even if the system is nonrelativistic. We show that the consistency of
      diffusive transport with this light cone places an upper bound on the
      diffusivity: D?v^{2}tau_{eq}. The operator growth velocity v defines the light
      cone, and tau_{eq} is the local equilibration time scale, beyond which the
      dynamics of conserved densities is diffusive. We verify that the bound is obeyed
      in various weakly and strongly interacting theories. In holographic models, this
      bound establishes a relation between the hydrodynamic and leading nonhydrodynamic
      quasinormal modes of planar black holes. Our bound relates transport data
      including the electrical resistivity and the shear viscosity-to the local
      equilibration time, even in the absence of a quasiparticle description. In this
      way, the bound sheds light on the observed T-linear resistivity of many
      unconventional metals, the shear viscosity of the quark-gluon plasma, and the
      spin transport of unitary fermions.

PMID- 29053286
TI  - Effective One-Dimensional Coupling in the Highly Frustrated Square-Lattice
      Itinerant Magnet CaCo_{2-y}As_{2}.
AB  - Inelastic neutron scattering measurements on the itinerant antiferromagnet
      CaCo_{2-y}As_{2} at a temperature of 8 K reveal two orthogonal planes of
      scattering perpendicular to the Co square lattice in reciprocal space,
      demonstrating the presence of effective one-dimensional spin interactions. These
      results are shown to arise from near-perfect bond frustration within the J_{1}
      J_{2} Heisenberg model on a square lattice with ferromagnetic J_{1} and hence
      indicate that the extensive previous experimental and theoretical study of the
      J_{1}-J_{2} Heisenberg model on local-moment square spin lattices should be
      expanded to include itinerant spin systems.

PMID- 29053287
TI  - General Criterion for Harmonicity.
AB  - Inspired by Kubo-Anderson Markov processes, we introduce a new class of transfer
      matrices whose largest eigenvalue is determined by a simple explicit algebraic
      equation. Applications include the free energy calculation for various
      equilibrium systems and a general criterion for perfect harmonicity, i.e., a free
      energy that is exactly quadratic in the external field. As an illustration, we
      construct a "perfect spring," namely, a polymer with non-Gaussian, exponentially
      distributed subunits which, nevertheless, remains harmonic until it is fully
      stretched. This surprising discovery is confirmed by Monte Carlo and Langevin
      simulations.

PMID- 29053288
TI  - Correlations and Entanglement of Microwave Photons Emitted in a Cascade Decay.
AB  - We use a three-level artificial atom in the ladder configuration as a source of
      correlated, single microwave photons of different frequency. The artificial atom,
      a transmon-type superconducting circuit, is driven at the two-photon transition
      between ground and second-excited state, and embedded into an on-chip switch that
      selectively routes different-frequency photons into different spatial modes.
      Under continuous driving, we measure power cross-correlations between the two
      modes and observe a crossover between strong antibunching and superbunching,
      typical of cascade decay, and an oscillatory pattern as the drive strength
      becomes comparable to the radiative decay rate. By preparing the source in a
      superposition state using an excitation pulse, we achieve deterministic
      generation of entangled photon pairs, as demonstrated by nonvanishing phase
      correlations and more generally by joint quantum state tomography of the two
      itinerant photonic modes.

PMID- 29053290
TI  - Extracting Entanglement Geometry from Quantum States.
AB  - Tensor networks impose a notion of geometry on the entanglement of a quantum
      system. In some cases, this geometry is found to reproduce key properties of
      holographic dualities, and subsequently much work has focused on using tensor
      networks as tractable models for holographic dualities. Conventionally, the
      structure of the network-and hence the geometry-is largely fixed a priori by the
      choice of the tensor network ansatz. Here, we evade this restriction and describe
      an unbiased approach that allows us to extract the appropriate geometry from a
      given quantum state. We develop an algorithm that iteratively finds a unitary
      circuit that transforms a given quantum state into an unentangled product state.
      We then analyze the structure of the resulting unitary circuits. In the case of
      noninteracting, critical systems in one dimension, we recover signatures of scale
      invariance in the unitary network, and we show that appropriately defined
      geodesic paths between physical degrees of freedom exhibit known properties of a
      hyperbolic geometry.

PMID- 29053289
TI  - Quantum Brownian Motion at Strong Dissipation Probed by Superconducting Tunnel
      Junctions.
AB  - We have investigated the phase dynamics of a superconducting tunnel junction at
      ultralow temperatures in the presence of high damping, where the interaction with
      environmental degrees of freedom represents the leading energy scale. In this
      regime, theory predicts the dynamics to follow a generalization of the classical
      Smoluchowski description, the quantum Smoluchowski equation, thus, exhibiting
      overdamped quantum Brownian motion characteristics. For this purpose, we have
      performed current-biased measurements on the small-capacitance Josephson junction
      of a scanning tunneling microscope placed in a low impedance environment at milli
      Kelvin temperatures. We can describe our experimental findings with high accuracy
      by using a quantum phase diffusion model based on the quantum Smoluchowski
      equation. In this way we experimentally demonstrate that overdamped quantum
      systems follow quasiclassical dynamics with significant quantum effects as the
      leading corrections.

PMID- 29053291
TI  - Double Helix Nodal Line Superconductor.
AB  - Time-reversal invariant superconductors in three dimensions may contain nodal
      lines in the Brillouin zone, which behave as Wilson loops of 3D momentum-space
      Chern-Simons theory of the Berry connection. Here we study the conditions of
      realizing linked nodal lines (Wilson loops), which yield a topological
      contribution to the thermal magnetoelectric coefficient that is given by the
      Chern-Simons action. We find the essential conditions are the existence of torus
      or higher genus Fermi surfaces and spiral spin textures. We construct such a
      model with two torus Fermi surfaces, where a generic spin-dependent interaction
      leads to double-helix-like linked nodal lines as the superconductivity is
      developed.

PMID- 29053292
TI  - High-Temperature Nonequilibrium Bose Condensation Induced by a Hot Needle.
AB  - We investigate theoretically a one-dimensional ideal Bose gas that is driven into
      a steady state far from equilibrium via the coupling to two heat baths: a global
      bath of temperature T and a "hot needle," a bath of temperature T_{h}?T with
      localized coupling to the system. Remarkably, this system features a crossover to
      finite-size Bose condensation at temperatures T that are orders of magnitude
      larger than the equilibrium condensation temperature. This counterintuitive
      effect is explained by a suppression of long-wavelength excitations resulting
      from the competition between both baths. Moreover, for sufficiently large needle
      temperatures ground-state condensation is superseded by condensation into an
      excited state, which is favored by its weaker coupling to the hot needle. Our
      results suggest a general strategy for the preparation of quantum degenerate
      nonequilibrium steady states with unconventional properties and at large
      temperatures.

PMID- 29053293
TI  - New Constraints on Light Vectors Coupled to Anomalous Currents.
AB  - We derive new constraints on light vectors coupled to standard model (SM)
      fermions, when the corresponding SM current is broken by the chiral anomaly. The
      cancellation of the anomaly by heavy fermions results, in the low-energy theory,
      in Wess-Zumino-type interactions between the new vector and the SM gauge bosons.
      These interactions are determined by the requirement that the heavy sector
      preserves the SM gauge groups and lead to (energy/vector mass)^{2} enhanced rates
      for processes involving the longitudinal mode of the new vector. Taking the
      example of a vector coupled to a vector coupled to SM baryon number, Z decays and
      flavor-changing neutral current meson decays via the new vector can occur with
      (weak scale/vector mass)^{2} enhanced rates. These processes place significantly
      stronger coupling bounds than others considered in the literature, over a wide
      range of vector masses.

PMID- 29053294
TI  - Passive Control of Viscous Flow via Elastic Snap-Through.
AB  - We demonstrate the passive control of viscous flow in a channel by using an
      elastic arch embedded in the flow. Depending on the fluid flux, the arch may
      "snap" between two states-constricting and unconstricting-that differ in
      hydraulic conductivity by up to an order of magnitude. We use a combination of
      experiments at a macroscopic scale and theory to study the constricting and
      unconstricting states, and determine the critical flux required to transition
      between them. We show that such a device may be precisely tuned for use in a
      range of applications, and, in particular, has potential as a passive
      microfluidic fuse to prevent excessive fluxes in rigid-walled channels.

PMID- 29053295
TI  - Self-Trapping Self-Repelling Random Walks.
AB  - Although the title seems self-contradictory, it does not contain a misprint. The
      model we study is a seemingly minor modification of the "true self-avoiding walk"
      model of Amit, Parisi, and Peliti in two dimensions. The walks in it are self
      repelling up to a characteristic time T^{*} (which depends on various
      parameters), but spontaneously (i.e., without changing any control parameter)
      become self-trapping after that. For free walks, T^{*} is astronomically large,
      but on finite lattices the transition is easily observable. In the self-trapped
      regime, walks are subdiffusive and intermittent, spending longer and longer times
      in small areas until they escape and move rapidly to a new area. In spite of
      this, these walks are extremely efficient in covering finite lattices, as
      measured by average cover times.

PMID- 29053296
TI  - Observation of Efimov Molecules Created from a Resonantly Interacting Bose Gas.
AB  - We convert a strongly interacting ultracold Bose gas into a mixture of atoms and
      molecules by sweeping the interactions from resonant to weak. By analyzing the
      decay dynamics of the molecular gas, we show that in addition to Feshbach dimers
      it contains Efimov trimers. Typically around 8% of the total atomic population is
      bound into trimers, identified by their density-independent lifetime of about 100
      MUs. The lifetime of the Feshbach dimers shows a density dependence due to
      inelastic atom-dimer collisions, in agreement with theoretical calculations. We
      also vary the density of the gas across a factor of 250 and investigate the
      corresponding atom loss rate at the interaction resonance.

PMID- 29053297
TI  - Quantum Emitters in Two-Dimensional Structured Reservoirs in the Nonperturbative
      Regime.
AB  - We show that the coupling of quantum emitters to a two-dimensional reservoir with
      a simple band structure gives rise to exotic quantum dynamics with no analogue in
      other scenarios and which cannot be captured by standard perturbative treatments.
      In particular, for a single quantum emitter with its transition frequency in the
      middle of the band, we predict an exponential relaxation at a rate different from
      that predicted by Fermi's golden rule, followed by overdamped oscillations and
      slow relaxation decay dynamics. This is accompanied by directional emission into
      the reservoir. This directionality leads to a modification of the emission rate
      for few emitters and even perfect subradiance, i.e., suppression of spontaneous
      emission, for four quantum emitters.

PMID- 29053298
TI  - Hyperinvariant Tensor Networks and Holography.
AB  - We propose a new class of tensor network state as a model for the AdS/CFT
      correspondence and holography. This class is demonstrated to retain key features
      of the multiscale entanglement renormalization ansatz (MERA), in that they
      describe quantum states with algebraic correlation functions, have free
      variational parameters, and are efficiently contractible. Yet, unlike the MERA,
      they are built according to a uniform tiling of hyperbolic space, without
      inherent directionality or preferred locations in the holographic bulk, and thus
      circumvent key arguments made against the MERA as a model for AdS/CFT. Novel
      holographic features of this tensor network class are examined, such as an
      equivalence between the causal cones C(R) and the entanglement wedges E(R) of
      connected boundary regions R.

PMID- 29053299
TI  - Two-Loop Four-Gluon Amplitudes from Numerical Unitarity.
AB  - We present the first numerical computation of two-loop amplitudes based on the
      unitarity method. As a proof of principle, we compute the four-gluon process in
      the leading-color approximation. We discuss the new method, analyze its numerical
      properties, and apply it to reconstruct the analytic form of the amplitudes. The
      numerical method is universal, and can be automated to provide multiscale two
      loop computations for phenomenologically relevant signatures at hadron colliders.

PMID- 29053300
TI  - Proximity Effects in Bilayer Graphene on Monolayer WSe_{2}: Field-Effect Spin
      Valley Locking, Spin-Orbit Valve, and Spin Transistor.
AB  - Proximity orbital and spin-orbit effects of bilayer graphene on monolayer WSe_{2}
      are investigated from first principles. We find that the built-in electric field
      induces an orbital band gap of about 10 meV in bilayer graphene. Remarkably, the
      proximity spin-orbit splitting for holes is 2 orders of magnitude-the spin-orbit
      splitting of the valence band at K is about 2 meV-more than for electrons.
      Effectively, holes experience spin valley locking due to the strong proximity of
      the lower graphene layer to WSe_{2}. However, applying an external transverse
      electric field of some 1  V/nm, countering the built-in field of the
      heterostructure, completely reverses this effect and allows, instead of holes,
      electrons to be spin valley locked with 2 meV spin-orbit splitting. Such a
      behavior constitutes a highly efficient field-effect spin-orbit valve, making
      bilayer graphene on WSe_{2} a potential platform for a field-effect spin
      transistor.

PMID- 29053301
TI  - Quantifying Genuine Multipartite Correlations and their Pattern Complexity.
AB  - We propose an information-theoretic framework to quantify multipartite
      correlations in classical and quantum systems, answering questions such as what
      is the amount of seven-partite correlations in a given state of ten particles? We
      identify measures of genuine multipartite correlations, i.e., statistical
      dependencies that cannot be ascribed to bipartite correlations, satisfying a set
      of desirable properties. Inspired by ideas developed in complexity science, we
      then introduce the concept of weaving to classify states that display different
      correlation patterns, but cannot be distinguished by correlation measures. The
      weaving of a state is defined as the weighted sum of correlations of every order.
      Weaving measures are good descriptors of the complexity of correlation structures
      in multipartite systems.

PMID- 29053302
TI  - Breaking Lorentz Reciprocity with Frequency Conversion and Delay.
AB  - We introduce a method for breaking Lorentz reciprocity based upon the
      noncommutation of frequency conversion and delay. The method requires no magnetic
      materials or resonant physics, allowing for the design of scalable and broadband
      nonreciprocal circuits. With this approach, two types of gyrators-universal
      building blocks for linear, nonreciprocal circuits-are constructed. Using one of
      these gyrators, we create a circulator with >15  dB of isolation across the 5-9
      GHz band. Our designs may be readily extended to any platform with suitable
      frequency conversion elements, including semiconducting devices for
      telecommunication or an on-chip superconducting implementation for quantum
      information processing.

PMID- 29053303
TI  - Phonon-Limited-Linewidth of Brillouin Lasers at Cryogenic Temperatures.
AB  - Laser linewidth is of central importance in spectroscopy, frequency metrology,
      and all applications of lasers requiring high coherence. It is also of
      fundamental importance, because the Schawlow-Townes laser linewidth limit is of
      quantum origin. Recently, a theory of stimulated Brillouin laser (SBL) linewidth
      has been reported. While the SBL linewidth formula exhibits power and optical Q
      factor dependences that are identical to the Schawlow-Townes formula, a source of
      noise not present in conventional lasers, phonon occupancy of the Brillouin
      mechanical mode is predicted to be the dominant SBL linewidth contribution.
      Moreover, the quantum limit of the SBL linewidth is predicted to be twice the
      Schawlow-Townes limit on account of phonon participation. To help confirm this
      theory the SBL fundamental linewidth is measured at cryogenic temperatures in a
      silica microresonator. Its temperature dependence and the SBL linewidth theory
      are combined to predict the number of thermomechanical quanta at three
      temperatures. The result agrees with the Bose-Einstein phonon occupancy of the
      microwave-rate Brillouin mode in support of the SBL linewidth theory prediction.

PMID- 29053304
TI  - Purification of Single Photons from Room-Temperature Quantum Dots.
AB  - Single photon emitters are indispensable to photonic quantum technologies. Here,
      we demonstrate waveform-controlled high-purity single photons from room
      temperature colloidal quantum dots. The purity of the single photons does not
      vary with the excitation power, thereby allowing the generation rate to be
      increased without compromising the single-photon quality.

PMID- 29053307
TI  - Light-Induced Anisotropic Skyrmion and Stripe Phases in a Rashba Ferromagnet.
AB  - An external off-resonant pumping is proposed as a tool to control the
      Dzyaloshinskii-Moriya interaction (DMI) in ferromagnetic layers with strong spin
      orbit coupling. Combining theoretical analysis with numerical simulations for an
      s-d-like model, we demonstrate that linearly polarized off-resonant light may
      help stabilize novel noncollinear magnetic phases by inducing a strong anisotropy
      of the DMI. We also investigate how with the application of electromagnetic
      pumping one can control the stability, shape, and size of individual Skyrmions to
      make them suitable for potential applications.

PMID- 29053308
TI  - Epidemic Dynamics in Open Quantum Spin Systems.
AB  - We explore the nonequilibrium evolution and stationary states of an open many
      body system that displays epidemic spreading dynamics in a classical and a
      quantum regime. Our study is motivated by recent experiments conducted in
      strongly interacting gases of highly excited Rydberg atoms where the facilitated
      excitation of Rydberg states competes with radiative decay. These systems
      approximately implement open quantum versions of models for population dynamics
      or disease spreading where species can be in a healthy, infected or immune state.
      We show that in a two-dimensional lattice, depending on the dominance of either
      classical or quantum effects, the system may display a different kind of
      nonequilibrium phase transition. We moreover discuss the observability of our
      findings in laser driven Rydberg gases with particular focus on the role of long
      range interactions.

PMID- 29053309
TI  - Non-Fermi Glasses: Localized Descendants of Fractionalized Metals.
AB  - Non-Fermi liquids are metals that cannot be adiabatically deformed into free
      fermion states. We argue for the existence of "non-Fermi glasses," phases of
      interacting disordered fermions that are fully many-body localized (MBL), yet
      cannot be deformed into an Anderson insulator without an eigenstate phase
      transition. We explore the properties of such non-Fermi glasses, focusing on a
      specific solvable example. At high temperature, non-Fermi glasses have
      qualitatively similar spectral features to Anderson insulators. We identify a
      diagnostic based on ratios of correlators that sharply distinguishes between the
      two phases even at infinite temperature. Our results and diagnostic should
      generically apply to the high-temperature behavior of MBL descendants of
      fractionalized phases.

PMID- 29053310
TI  - Local Pore Size Correlations Determine Flow Distributions in Porous Media.
AB  - The relationship between the microstructure of a porous medium and the observed
      flow distribution is still a puzzle. We resolve it with an analytical model,
      where the local correlations between adjacent pores, which determine the
      distribution of flows propagated from one pore downstream, predict the flow
      distribution. Numerical simulations of a two-dimensional porous medium verify the
      model and clearly show the transition of flow distributions from delta-function
      like via Gaussians to exponential with increasing disorder. Comparison to
      experimental data further verifies our numerical approach.

PMID- 29053311
TI  - Inducing and Manipulating Heteroelectronic States in a Single MoS_{2} Thin Flake.
AB  - By dual gating a few-layer MoS_{2} flake, we induce spatially separated
      electronic states showing superconductivity and Shubnikov-de Haas (SdH)
      oscillations. While the highly confined superconductivity forms at the K/K^{'}
      valleys of the topmost layer, the SdH oscillations are contributed by the
      electrons residing in the Q/Q^{'} valleys of the rest of the bottom layers, which
      is confirmed by the extracted Landau level degeneracy of 3, electron effective
      mass of 0.6m_{e}, and carrier density of 5*10^{12}  cm^{-2}. Mimicking
      conventional heterostructures, the interaction between the heteroelectronic
      states can be electrically manipulated, which enables "bipolarlike"
      superconducting transistor operation. The off-on-off switching pattern can be
      continuously accessed at low temperatures by a field effect depletion of carriers
      with a negative back gate bias and the proximity effect between the top
      superconducting layer and the bottom metallic layers that quenches the
      superconductivity at a positive back gate bias.

PMID- 29053312
TI  - Topological Transitions and Fractional Charges Induced by Strain and a Magnetic
      Field in Carbon Nanotubes.
AB  - We show that carbon nanotubes (CNT) can be driven through a topological phase
      transition using either strain or a magnetic field. This can naturally lead to
      Jackiw-Rebbi soliton states carrying fractionalized charges, similar to those
      found in a domain wall in the Su-Schrieffer-Heeger model, in a setup with a
      spatially inhomogeneous strain and an axial field. Two types of fractionalized
      states can be formed at the interface between regions with different strain: a
      spin-charge separated state with integer charge and spin zero (or zero charge and
      spin +/-h/2), and a state with charge +/-e/2 and spin +/-h/4. The latter state
      requires spin-orbit coupling in the CNT. We show that in our setup, the precise
      quantization of the fractionalized interface charges is a consequence of the
      symmetry of the CNT under a combination of a spatial rotation by pi and time
      reversal.

PMID- 29053313
TI  - Strong Anisotropic Interaction Controls Unusual Sticking and Scattering of CO at
      Ru(0001).
AB  - Complete sticking at low incidence energies and broad angular scattering
      distributions at higher energies are often observed in molecular beam experiments
      on gas-surface systems which feature a deep chemisorption well and lack early
      reaction barriers. Although CO binds strongly on Ru(0001), scattering is
      characterized by rather narrow angular distributions and sticking is incomplete
      even at low incidence energies. We perform molecular dynamics simulations,
      accounting for phononic (and electronic) energy loss channels, on a potential
      energy surface based on first-principles electronic structure calculations that
      reproduce the molecular beam experiments. We demonstrate that the mentioned
      unusual behavior is a consequence of a very strong rotational anisotropy in the
      molecule-surface interaction potential. Beyond the interpretation of scattering
      phenomena, we also discuss implications of our results for the recently proposed
      role of a precursor state for the desorption and scattering of CO from ruthenium.

PMID- 29053314
TI  - Theory of Turing Patterns on Time Varying Networks.
AB  - The process of pattern formation for a multispecies model anchored on a time
      varying network is studied. A nonhomogeneous perturbation superposed to an
      homogeneous stable fixed point can be amplified following the Turing mechanism of
      instability, solely instigated by the network dynamics. By properly tuning the
      frequency of the imposed network evolution, one can make the examined system
      behave as its averaged counterpart, over a finite time window. This is the key
      observation to derive a closed analytical prediction for the onset of the
      instability in the time dependent framework. Continuously and piecewise constant
      periodic time varying networks are analyzed, setting the framework for the
      proposed approach. The extension to nonperiodic settings is also discussed.

PMID- 29053315
TI  - Shear Modulus and Shear-Stress Fluctuations in Polymer Glasses.
AB  - Using molecular dynamics simulation of a standard coarse-grained polymer glass
      model, we investigate by means of the stress-fluctuation formalism the shear
      modulus MU as a function of temperature T and sampling time Deltat. While the
      ensemble-averaged modulus MU(T) is found to decrease continuously for all Deltat
      sampled, its standard deviation deltaMU(T) is nonmonotonic, with a striking peak
      at the glass transition. Confirming the effective time-translational invariance
      of our systems, MU(Deltat) can be understood using a weighted integral over the
      shear-stress relaxation modulus G(t). While the crossover of MU(T) gets sharper
      with an increasing Deltat, the peak of deltaMU(T) becomes more singular. It is
      thus elusive to predict the modulus of a single configuration at the glass
      transition.

PMID- 29053316
TI  - Nucleon Spin and Momentum Decomposition Using Lattice QCD Simulations.
AB  - We determine within lattice QCD the nucleon spin carried by valence and sea
      quarks and gluons. The calculation is performed using an ensemble of gauge
      configurations with two degenerate light quarks with mass fixed to approximately
      reproduce the physical pion mass. We find that the total angular momentum carried
      by the quarks in the nucleon is J_{u+d+s}=0.408(61)_{stat}(48)_{syst} and the
      gluon contribution is J_{g}=0.133(11)_{stat}(14)_{syst}, giving a total of
      J_{N}=0.54(6)_{stat}(5)_{syst} that is consistent with the spin sum. For the
      quark intrinsic spin contribution, we obtain
      1/2DeltaSigma_{u+d+s}=0.201(17)_{stat}(5)_{syst}. All quantities are given in the
      modified minimal subtraction scheme at 2 GeV. The quark and gluon momentum
      fractions are also computed and add up to
      ?x?_{u+d+s}+?x?_{g}=0.804(121)_{stat}(95)_{syst}+0.267(12)_{stat}(10)_{syst}=1.07
      12)_{stat}(10)_{syst}, thus satisfying the momentum sum.

PMID- 29053318
TI  - Generic Properties of Stochastic Entropy Production.
AB  - We derive an Ito stochastic differential equation for entropy production in
      nonequilibrium Langevin processes. Introducing a random-time transformation,
      entropy production obeys a one-dimensional drift-diffusion equation, independent
      of the underlying physical model. This transformation allows us to identify
      generic properties of entropy production. It also leads to an exact uncertainty
      equality relating the Fano factor of entropy production and the Fano factor of
      the random time, which we also generalize to non-steady-state conditions.

PMID- 29053317
TI  - Supercoiling DNA Locates Mismatches.
AB  - We present a method of detecting sequence defects by supercoiling DNA with
      magnetic tweezers. The method is sensitive to a single mismatched base pair in a
      DNA sequence of several thousand base pairs. We systematically compare DNA
      molecules with 0 to 16 adjacent mismatches at 1 M monovalent salt and 3.6 pN
      force and show that under these conditions, a single plectoneme forms and is
      stably pinned at the defect. We use these measurements to estimate the energy and
      degree of end-loop kinking at defects. From this, we calculate the relative
      probability of plectoneme pinning at the mismatch under physiologically relevant
      conditions. Based on this estimate, we propose that DNA supercoiling could
      contribute to mismatch and damage sensing in vivo.

PMID- 29053319
TI  - Holonomic Quantum Control by Coherent Optical Excitation in Diamond.
AB  - Although geometric phases in quantum evolution are historically overlooked, their
      active control now stimulates strategies for constructing robust quantum
      technologies. Here, we demonstrate arbitrary single-qubit holonomic gates from a
      single cycle of nonadiabatic evolution, eliminating the need to concatenate two
      separate cycles. Our method varies the amplitude, phase, and detuning of a two
      tone optical field to control the non-Abelian geometric phase acquired by a
      nitrogen-vacancy center in diamond over a coherent excitation cycle. We
      demonstrate the enhanced robustness of detuned gates to excited-state decoherence
      and provide insights for optimizing fast holonomic control in dissipative quantum
      systems.

PMID- 29053320
TI  - Interplay between Process Zone and Material Heterogeneities for Dynamic Cracks.
AB  - Using an elastodynamic boundary integral formulation coupled with a cohesive
      model, we study the problem of a dynamic rupture front propagating along an
      heterogeneous plane. We show that small-scale heterogeneities facilitate the
      supershear transition of a mode-II crack. The elastic pulses radiated during
      front accelerations explain how microscopic variations of fracture toughness
      change the macroscopic rupture dynamics. Perturbations of dynamic fronts are then
      systematically studied with different microstructures and loading conditions. The
      process zone size is the intrinsic length scale controlling heterogeneous dynamic
      rupture. The ratio of this length scale to asperity size is proposed as an
      indicator to transition from quasihomogeneous to heterogeneous fracture.
      Moreover, we discuss how the shortening of the process zone size with increasing
      crack speed brings the front to interact with smaller details of the
      microstructure. This study shines new light on recent experiments reporting
      perturbations of dynamic rupture fronts, which intensify with crack propagation
      speed.

PMID- 29053321
TI  - Universal Limit on Communication.
AB  - I derive a universal upper bound on the capacity of any communication channel
      between two distant systems. The Holevo quantity, and hence the mutual
      information, is at most of order EDeltat/h, where E is the average energy of the
      signal, and Deltat is the amount of time for which detectors operate. The bound
      does not depend on the size or mass of the emitting and receiving systems, nor on
      the nature of the signal. No restrictions on preparing and processing the signal
      are imposed. As an example, I consider the encoding of information in the
      transverse or angular position of a signal emitted and received by systems of
      arbitrarily large cross section. In the limit of a large message space, quantum
      effects become important even if individual signals are classical, and the bound
      is upheld.

PMID- 29053323
TI  - When the Hotter Cools More Quickly: Mpemba Effect in Granular Fluids.
AB  - Under certain conditions, two samples of fluid at different initial temperatures
      present a counterintuitive behavior known as the Mpemba effect: it is the hotter
      system that cools sooner. Here, we show that the Mpemba effect is present in
      granular fluids, both in uniformly heated and in freely cooling systems. In both
      cases, the system remains homogeneous, and no phase transition is present.
      Analytical quantitative predictions are given for how differently the system must
      be initially prepared to observe the Mpemba effect, the theoretical predictions
      being confirmed by both molecular dynamics and Monte Carlo simulations. Possible
      implications of our analysis for other systems are also discussed.

PMID- 29053322
TI  - Strong Coupling of Microwave Photons to Antiferromagnetic Fluctuations in an
      Organic Magnet.
AB  - Coupling between a crystal of di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium
      radicals and a superconducting microwave resonator is investigated in a circuit
      quantum electrodynamics (circuit QED) architecture. The crystal exhibits
      paramagnetic behavior above 4 K, with antiferromagnetic correlations appearing
      below this temperature, and we demonstrate strong coupling at base temperature.
      The magnetic resonance acquires a field angle dependence as the crystal is cooled
      down, indicating anisotropy of the exchange interactions. These results show that
      multispin modes in organic crystals are suitable for circuit QED, offering a
      platform for their coherent manipulation. They also utilize the circuit QED
      architecture as a way to probe spin correlations at low temperature.

PMID- 29053324
TI  - Variability and Order in Cytoskeletal Dynamics of Motile Amoeboid Cells.
AB  - The chemotactic motion of eukaryotic cells such as leukocytes or metastatic
      cancer cells relies on membrane protrusions driven by the polymerization and
      depolymerization of actin. Here we show that the response of the actin system to
      a receptor stimulus is subject to a threshold value that varies strongly from
      cell to cell. Above the threshold, we observe pronounced cell-to-cell variability
      in the response amplitude. The polymerization time, however, is almost constant
      over the entire range of response amplitudes, while the depolymerization time
      increases with increasing amplitude. We show that cell-to-cell variability in the
      response amplitude correlates with the amount of Arp2/3, a protein that enhances
      actin polymerization. A time-delayed feedback model for the cortical actin
      concentration is consistent with all our observations and confirms the role of
      Arp2/3 in the observed cell-to-cell variability. Taken together, our observations
      highlight robust regulation of the actin response that enables a reliable timing
      of cell movement.

PMID- 29053325
TI  - Assessing Density Functionals Using Many Body Theory for Hybrid Perovskites.
AB  - Which density functional is the "best" for structure simulations of a particular
      material? A concise, first principles, approach to answer this question is
      presented. The random phase approximation (RPA)-an accurate many body theory-is
      used to evaluate various density functionals. To demonstrate and verify the
      method, we apply it to the hybrid perovskite MAPbI_{3}, a promising new solar
      cell material. The evaluation is done by first creating finite temperature
      ensembles for small supercells using RPA molecular dynamics, and then evaluating
      the variance between the RPA and various approximate density functionals for
      these ensembles. We find that, contrary to recent suggestions, van der Waals
      functionals do not improve the description of the material, whereas hybrid
      functionals and the strongly constrained appropriately normed (SCAN) density
      functional yield very good agreement with the RPA. Finally, our study shows that
      in the room temperature tetragonal phase of MAPbI_{3}, the molecules are
      preferentially parallel to the shorter lattice vectors but reorientation on ps
      time scales is still possible.

PMID- 29053326
TI  - Magnetoquantum Oscillations at THz Frequencies in InSb.
AB  - The ac magnetoconductance of bulk InSb at THz frequencies in high magnetic
      fields, as measured by the transmission of THz radiation, shows a field-induced
      transmission, which at high temperatures (~100  K) is well explained with
      classical magnetoplasma effects (helicon waves). However, at low temperatures (4
      K), the transmitted radiation intensity shows magnetoquantum oscillations that
      represent the Shubnikov-de Haas effect at THz frequencies. At frequencies above
      0.9 THz, when the radiation period is shorter than the Drude scattering time, an
      anomalously high transmission is observed in the magnetic quantum limit that can
      be interpreted as carrier localization at high frequencies.

PMID- 29053327
TI  - Exact Identification of a Quantum Change Point.
AB  - The detection of change points is a pivotal task in statistical analysis. In the
      quantum realm, it is a new primitive where one aims at identifying the point
      where a source that supposedly prepares a sequence of particles in identical
      quantum states starts preparing a mutated one. We obtain the optimal procedure to
      identify the change point with certainty-naturally at the price of having a
      certain probability of getting an inconclusive answer. We obtain the analytical
      form of the optimal probability of successful identification for any length of
      the particle sequence. We show that the conditional success probabilities of
      identifying each possible change point show an unexpected oscillatory behavior.
      We also discuss local (online) protocols and compare them with the optimal
      procedure.

PMID- 29053328
TI  - QCD-Electroweak First-Order Phase Transition in a Supercooled Universe.
AB  - If the electroweak sector of the standard model is described by classically
      conformal dynamics, the early Universe evolution can be substantially altered. It
      is already known that-contrarily to the standard model case-a first-order
      electroweak phase transition may occur. Here we show that, depending on the model
      parameters, a dramatically different scenario may happen: A first-order, six
      massless quark QCD phase transition occurs first, which then triggers the
      electroweak symmetry breaking. We derive the necessary conditions for this
      dynamics to occur, using the specific example of the classically conformal B-L
      model. In particular, relatively light weakly coupled particles are predicted,
      with implications for collider searches. This scenario is also potentially rich
      in cosmological consequences, such as renewed possibilities for electroweak
      baryogenesis, altered dark matter production, and gravitational wave production,
      as we briefly comment upon.

PMID- 29053329
TI  - Investigating Anisotropic Quantum Hall States with Bimetric Geometry.
AB  - We construct a low energy effective theory of anisotropic fractional quantum Hall
      (FQH) states. We develop a formalism similar to that used in the bimetric
      approach to massive gravity, and apply it to describe Abelian anisotropic FQH
      states in the presence of external electromagnetic and geometric backgrounds. We
      derive a relationship between the shift, the Hall viscosity, and a new quantized
      coupling to anisotropy, which we term anisospin. We verify this relationship by
      numerically computing the Hall viscosity for a variety of anisotropic quantum
      Hall states using the density matrix renormalization group. Finally, we apply
      these techniques to the problem of nematic order and clarify certain
      disagreements that exist in the literature about the meaning of the coefficient
      of the Berry phase term in the nematic effective action.

PMID- 29053330
TI  - Electrodynamics on Fermi Cyclides in Nodal Line Semimetals.
AB  - We study the frequency-dependent conductivity of nodal line semimetals (NLSMs),
      focusing on the effects of carrier density and energy dispersion on the nodal
      line. We find that the low-frequency conductivity has a rich spectral structure
      which can be understood using scaling rules derived from the geometry of their
      Dupin cyclide Fermi surfaces. We identify different frequency regimes, find
      scaling rules for the optical conductivity in each, and demonstrate them with
      numerical calculations of the inter- and intraband contributions to the optical
      conductivity using a low-energy model for a generic NLSM.

PMID- 29053331
TI  - Long-Lived Ultracold Molecules with Electric and Magnetic Dipole Moments.
AB  - We create fermionic dipolar ^{23}Na^{6}Li molecules in their triplet ground state
      from an ultracold mixture of ^{23}Na and ^{6}Li. Using magnetoassociation across
      a narrow Feshbach resonance followed by a two-photon stimulated Raman adiabatic
      passage to the triplet ground state, we produce 3*10^{4} ground state molecules
      in a spin-polarized state. We observe a lifetime of 4.6 s in an isolated
      molecular sample, approaching the p-wave universal rate limit. Electron spin
      resonance spectroscopy of the triplet state was used to determine the hyperfine
      structure of this previously unobserved molecular state.

PMID- 29053332
TI  - Radiatively Generating the Higgs Potential and Electroweak Scale via the Seesaw
      Mechanism.
AB  - The minimal seesaw scenario can radiatively generate the Higgs potential to
      induce electroweak symmetry breaking while supplying an origin of the Higgs
      vacuum expectation value from an underlying Majorana scale. If the Higgs
      potential and (derived) electroweak scale have this origin, the heavy
      SU(3)*SU(2)*U(1)_{Y} singlet states are expected to reside at m_{N}~10-500  PeV
      for couplings |omega|~10^{-4.5}-10^{-6} between the Majorana sector and the
      standard model. In this framework, the usual challenge of the electroweak scale
      hierarchy problem with a classically assumed potential is absent as the
      electroweak scale is not a fundamental scale. The new challenge is the need to
      generate or accommodate PeV Majorana mass scales while simultaneously suppressing
      tree-level contributions to the potential in ultraviolet models.

PMID- 29053333
TI  - Spin Resonance Clock Transition of the Endohedral Fullerene ^{15}N@C_{60}.
AB  - The endohedral fullerene ^{15}N@C_{60} has narrow electron paramagnetic resonance
      lines which have been proposed as the basis for a condensed-matter portable
      atomic clock. We measure the low-frequency spectrum of this molecule, identifying
      and characterizing a clock transition at which the frequency becomes insensitive
      to magnetic field. We infer a linewidth at the clock field of 100 kHz. Using
      experimental data, we are able to place a bound on the clock's projected
      frequency stability. We discuss ways to improve the frequency stability to be
      competitive with existing miniature clocks.

PMID- 29053334
TI  - Topological Phase Transitions in the Photonic Spin Hall Effect.
AB  - The recent synthesis of two-dimensional staggered materials opens up burgeoning
      opportunities to study optical spin-orbit interactions in semiconducting Dirac
      like systems. We unveil topological phase transitions in the photonic spin Hall
      effect in the graphene family materials. It is shown that an external static
      electric field and a high frequency circularly polarized laser allow for active
      on-demand manipulation of electromagnetic beam shifts. The spin Hall effect of
      light presents a rich dependence with radiation degrees of freedom, and material
      properties, and features nontrivial topological properties. We discover that
      photonic Hall shifts are sensitive to spin and valley properties of the charge
      carriers, providing an unprecedented pathway to investigate spintronics and
      valleytronics in staggered 2D semiconductors.

PMID- 29053335
TI  - Success rates of a skeletal anchorage system in orthodontics: A retrospective
      analysis.
AB  - OBJECTIVES: To evaluate the premise that skeletal anchorage with SAS miniplates
      are highly successful and predictable for a range of complex orthodontic
      movements. MATERIALS AND METHODS: This retrospective cross-sectional analysis
      consisted of 421 bone plates placed by one clinician in 163 patients (95 female,
      68 male, mean age 29.4 years +/- 12.02). Simple descriptive statistics were
      performed for a wide range of malocclusions and desired movements to obtain
      success, complication, and failure rates. RESULTS: The success rate of skeletal
      anchorage system miniplates was 98.6%, where approximately 40% of cases
      experienced mild complications. The most common complication was soft tissue
      inflammation, which was amenable to focused oral hygiene and antiseptic rinses.
      Infection occurred in approximately 15% of patients where there was a
      statistically significant correlation with poor oral hygiene. The most common
      movements were distalization and intrusion of teeth. More than a third of the
      cases involved complex movements in more than one plane of space. CONCLUSIONS:
      The success rate of skeletal anchorage system miniplates is high and predictable
      for a wide range of complex orthodontic movements.

PMID- 29053337
TI  - Obesity and Severity of Acute Exacerbation of Chronic Obstructive Pulmonary
      Disease.
AB  - RATIONALE: Obesity is relatively common among individuals with chronic
      obstructive pulmonary disease (COPD). However, little is known about the
      association of obesity with severity of acute exacerbation of COPD and in
      hospital mortality. OBJECTIVES: To examine the association of obesity with
      markers of severity of acute exacerbation of COPD and in-hospital mortality.
      METHODS: This is a population-based, retrospective cohort study using the 2012
      2013 State Inpatient Databases of seven U.S. states (Arkansas, Florida, Iowa,
      Nebraska, New York, Utah, and Washington). We included adults (aged >=40 yr)
      hospitalized for acute exacerbation of COPD. Obesity, use of noninvasive positive
      pressure ventilation (NIPPV), and use of invasive mechanical ventilation were
      determined by International Classification of Diseases, Ninth Revision codes. To
      examine associations between obesity and each outcome (NIPPV, invasive mechanical
      ventilation, hospital length of stay (LOS), and in-hospital mortality), we fit
      unadjusted and adjusted logistic regression models using generalized estimating
      equations to account for patient clustering within hospitals. We adjusted for
      age, sex, race/ethnicity, primary payer, median household income, patient
      residence, hospitalization year, chronic comorbidities, and hospital state. In
      the sensitivity analysis, we used stabilized inverse probability weighting to
      estimate the causal relation of obesity with outcomes in this observational
      study. RESULTS: Of 187,647 patients hospitalized for an acute exacerbation of
      COPD, 17% were obese. Obesity was associated with increased use of both NIPPV
      (12.0% vs. 6.5%; adjusted odds ratio [OR] = 1.86; 95% confidence interval [CI] =
      1.77-1.95; P < 0.001) and invasive mechanical ventilation (3.5% vs. 2.8%;
      adjusted OR = 1.13; 95% CI = 1.04-1.22; P = 0.003). Similarly, obese patients
      were more likely to have a hospital LOS of 4 days or longer (57.9% vs. 50.3%;
      adjusted OR = 1.37; 95% CI = 1.33-1.41; P < 0.001). In contrast, obesity was
      associated with a lower in-hospital mortality (0.9% vs. 1.4%; unadjusted OR =
      0.63; 95% CI = 0.56-0.72; P < 0.001). After adjusting for potential confounders,
      this association was no longer statistically significant (adjusted OR = 0.86; 95%
      CI = 0.75-1.00; P = 0.06). Results were similar in sensitivity analyses using
      stabilized inverse probability weighting. CONCLUSIONS: In this population-based
      study of adults hospitalized with an acute exacerbation of COPD, obesity was
      associated with increased use of noninvasive and invasive ventilation, increased
      hospital LOS, but was not associated with increased in-hospital mortality.

PMID- 29053336
TI  - Interplay between EZH2 and G9a Regulates CXCL10 Gene Repression in Idiopathic
      Pulmonary Fibrosis.
AB  - Selective repression of the antifibrotic gene CXCL10 contributes to tissue
      remodeling in idiopathic pulmonary fibrosis (IPF). We have previously reported
      that histone deacetylation and histone H3 lysine 9 (H3K9) methylation are
      involved in CXCL10 repression. In this study, we explored the role of H3K27
      methylation and the interplay between the two histone lysine methyltransferases
      enhancer of zest homolog 2 (EZH2) and G9a in CXCL10 repression in IPF. By
      applying chromatin immunoprecipitation, Re-ChIP, and proximity ligation assays,
      we demonstrated that, like G9a-mediated H3K9 methylation, EZH2-mediated histone
      H3 lysine 27 trimethylation (H3K27me3) was significantly enriched at the CXCL10
      promoter in fibroblasts from IPF lungs (F-IPF) compared with fibroblasts from
      nonfibrotic lungs, and we also found that EZH2 and G9a physically interacted with
      each other. EZH2 knockdown reduced not only EZH2 and H3K27me3 but also G9a and
      H3K9me3, and G9a knockdown reduced not only G9 and H3K9me3 but also EZH2 and
      H3K27me3. Depletion and inhibition of EZH2 and G9a also reversed histone
      deacetylation and restored CXCL10 expression in F-IPF. Furthermore, treatment of
      fibroblasts from nonfibrotic lungs with the profibrotic cytokine transforming
      growth factor-beta1 increased EZH2, G9a, H3K27me3, H3K9me3, and histone
      deacetylation at the CXCL10 promoter, similar to that observed in F-IPF, which
      was correlated with CXCL10 repression and was prevented by EZH2 and G9a
      knockdown. These findings suggest that a novel and functionally interdependent
      interplay between EZH2 and G9a regulates histone methylation-mediated epigenetic
      repression of the antifibrotic CXCL10 gene in IPF. This interdependent interplay
      may prove to be a target for epigenetic intervention to restore the expression of
      CXCL10 and other antifibrotic genes in IPF.

PMID- 29053338
TI  - Disaccharides Determination: A Review of Analytical Methods.
AB  - Disaccharides are determined mainly for dietetic purposes, hence the most
      analyses are carried out for food and drink samples. Its content can also be used
      to profile groceries in order to identify the origin and quality of the products.
      They also can be an indicator of the rate of metabolism as well as for the
      control of some technological and biotechnological processes. Unfortunately most
      of technological analysis are performed with nonselective polarimetry methods.
      Sugars due to specific physicochemical properties of compounds are difficult to
      determine with classical analytical techniques. The most common disaccharides are
      composed of several types of monomers connected by a different configuration of
      the glycosidic bond, therefore, there are subject of the same characteristic
      reactions. This often enforces the need for pre-separation of sample components.
      Therefore, nowadays the most popular analytical methodologies for disaccharides
      determination are based on chromatographic and electrophoretic techniques. An
      alternative is enzymes application that allow both selective recognition of
      target analyte and its conversion to easy detected product, allowing detection by
      relatively simple conventional analytical methods. Another approach is the use of
      advanced chemometric methodologies for computing of data obtained from some
      spectroscopic techniques. This article is a review of the recent analytical
      literature devoted to non-selective and selective methods for disaccharide
      determination in real samples.

PMID- 29053339
TI  - Extracellular Matrix Cross-Linking Enhances Fibroblast Growth and Protects
      against Matrix Proteolysis in Lung Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by accumulation of
      extracellular matrix (ECM) proteins and fibroblast proliferation. ECM cross
      linking enzymes have been implicated in fibrotic diseases, and we hypothesized
      that the ECM in IPF is abnormally cross-linked, which enhances fibroblast growth
      and resistance to normal ECM turnover. We used a combination of in vitro ECM
      preparations and in vivo assays to examine the expression of cross-linking
      enzymes and the effect of their inhibitors on fibroblast growth and ECM turnover.
      Lysyl oxidase-like 1 (LOXL1), LOXL2, LOXL3, and LOXL4 were expressed equally in
      control and IPF-derived fibroblasts. Transglutaminase 2 was more strongly
      expressed in IPF fibroblasts. LOXL2-, transglutaminase 2-, and transglutaminase
      generated cross-links were strongly expressed in IPF lung tissue. Fibroblasts
      grown on IPF ECM had higher LOXL3 protein expression and transglutaminase
      activity than those grown on control ECM. IPF-derived ECM also enhanced
      fibroblast adhesion and proliferation compared with control ECM. Inhibition of
      lysyl oxidase and transglutaminase activity during ECM formation affected ECM
      structure as visualized by electron microscopy, and it reduced the enhanced
      fibroblast adhesion and proliferation of IPF ECM to control levels. Inhibition of
      transglutaminase, but not of lysyl oxidase, activity enhanced the turnover of ECM
      in vitro. In bleomycin-treated mice, during the postinflammatory fibrotic phase,
      inhibition of transglutaminases was associated with a reduction in whole-lung
      collagen. Our findings suggest that the ECM in IPF may enhance pathological cross
      linking, which contributes to increased fibroblast growth and resistance to
      normal ECM turnover to drive lung fibrosis.

PMID- 29053340
TI  - The beneficial role of potassium in Cd-induced stress alleviation and growth
      improvement in Gladiolus grandiflora L.
AB  - Heavy metal contaminated agricultural soils are one of the most important
      constraints for successful cultivation of crops. The current research was
      conducted to evaluate the role of potassium (K) on plant growth and amelioration
      of cadmium (Cd) stress in Gladiolus grandiflora under greenhouse conditions. G.
      grandiflora corms were sown in media contaminated with 0 (C), 50 (Cd50) and 100
      (Cd100) mg Cd kg-1 soil. The plants growing in Cd-contaminated media exhibited
      reduced gas exchange attributes, chlorophyll (Chl) contents, vegetative and
      reproductive growth as compared to control. The plants raised in Cd contaminated
      media showed reduced nutrition yet higher Cd contents. However, supplementation
      of 60 mg Kg-1 K in treated plants (C+K, Cd50+K and Cd100+K) improved quantity of
      total soluble protein and proline (Pro) along with activity of antioxidant
      enzymes including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD)
      and ascorbate peroxidase (APX) under Cd stress. Similarly, K supplementation
      reduced the level of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in
      treated plants. Potassium supplemented plants exhibited better vegetative and
      reproductive growth. The improved stress tolerance in K supplemented plants was
      attributed to the reduced quantity of MDA and H2O2, enhanced synthesis of
      protein, proline, phenols, flavonides and improved activity of antioxidant
      enzymes. The present research supports the application of K for alleviation of Cd
      stress in G. grandiflora.

PMID- 29053341
TI  - Water potential in soil and Atriplex nummularia (phytoremediator halophyte) under
      drought and salt stresses.
AB  - Atriplex nummularia is a halophyte widely employed to recover saline soils and
      was used as a model to evaluate the water potentials in the soil-plant system
      under drought and salt stresses. Potted plants grown under 70 and 37% of field
      capacity irrigated with solutions of NaCl and of a mixture of NaCl, KCl, MgCl2
      and CaCl2 reproducing six electrical conductivity (EC): 0, 5, 10, 20, 30, and 40
      dS m-1. After 100 days, total water (Psiw, plant) and osmotic (Psio, plant)
      potentials at predawn and midday and Psio, soil, matric potential (Psim, soil)
      and Psiw, soil were determined. The type of ion in the irrigation water did not
      influence the soil potential, but was altered by EC. The soil Psio component was
      the largest contributor to Psiw, soil. Atriplex is surviving ECs close to 40 dS m
      1 due to the decrease in the Psiw. The plants reached a Psiw of approximately -8
      MPa. The water potentials determined for different moisture levels, EC levels and
      salt types showed huge importance for the management of this species in semiarid
      regions and can be used to recover salt affected soils.

PMID- 29053342
TI  - Lead phytoextraction from printed circuit computer boards by Lolium perenne L.
      and Medicago sativa L.
AB  - This work assessed the ability of Lolium perenne and Medicago sativa for
      extracting lead (Pb) from particulate printed circuit computer boards (PCB) mixed
      in sand with the following concentrations: 0.5, 1.0 and 1.5 g of PCB, and
      including a control treatment without PCB. The PCB were obtained from computers,
      and grinded in two particle sizes: 0.0594 mm (PCB1) and 0.0706 mm (PCB2). The PCB
      particle sizes at their corresponding concentrations were applied to L. perenne
      and M. sativa by using three experimental assays. In assay II, PCB2 affected the
      biomass production for both plants. For assay III, the PCB1 increased the biomass
      of M. sativa (236.5%) and L. perenne (142.2%) when applying either 0.5 or 1.0 g,
      respectively. In regards to phytoextraction, assay I showed the highest Pb
      extraction by roots of L. perenne (4.7%) when exposed to 1.5 g of PCB1. At assay
      I, L. perenne showed a Pb-bioconcentration factor higher than 1.0 when growing at
      0.5 g of PCB1, and when HNO3 was used as digestion solution; moreover, in assay
      III both plants showed a Pb-translocation factor higher than 1.0. Therefore,
      Lolium perenne and Medicago sativa are able to recover Pb from electronic wastes
      (PCB).

PMID- 29053343
TI  - Efficiency of Opuntia ficus in the phytoremediation of a soil contaminated with
      used motor oil and lead, compared to that of Lolium perenne and Aloe barbadensis.
AB  - Industrial pollutants such as heavy metals and hydrocarbons in soils represent a
      serious concern due to their persistence and negative effects on the environment,
      affecting cellular processes in living organisms and even causing mutations and
      cancer. The main objectives of this work were to evaluate the efficiency of
      Opuntia ficus in the phytoremediation of a soil polluted with used motor oil. Two
      other species, one with different and one with similar characteristics,
      relatively, were used for comparison purposes: Lolium perenne and Aloe
      barbadensis. The effect of the plants on lead solubility and bioaccumulation, the
      biomass production of each specie and the microbial counts and bacterial
      identification for each experiment was studied. Total petroleum hydrocarbons
      (TPH) were measured every 5 weeks throughout the 20-week phytoremediation
      experiment. At the end of the experiment soluble Pb, Pb extracted by the plant
      species, microbiological counts, total biomass and bacterial species in soil were
      analyzed. Even though Lolium perenne showed the highest TPH removal (47%),
      Opuntia ficus produced the highest biomass and similar removal (46%). Since
      Opuntia ficus requires low amounts of water and grows fast, it would be a
      suitable option in the remediation of soils polluted with hydrocarbons and/or
      heavy metals.

PMID- 29053344
TI  - Efficient bioremediation of tannery wastewater by monostrains and consortium of
      marine Chlorella sp. and Phormidium sp.
AB  - This study evaluated the bioremediation potential of two marine microalgae
      Chlorella sp. and Phormidium sp., both individually and in consortium, to reduce
      various pollutants in tannery wastewater (TW). The microalgae were grown in
      hazardous 100% TW for 20 days, and the reductions in biochemical oxygen demand
      (BOD), chemical oxygen demand (COD), total nitrogen (TN), total phosphorous (TP),
      chromium (Cr) and total dissolved solids (TDS) of the wastewater monitored
      periodically. Both marine isolates reduced the BOD and COD by >=90% in the
      consortium and by over 80% individually. Concentrations of TN and TP were reduced
      by 91.16% and 88%, respectively, by the consortium. Removal/biosorption
      efficiencies for chromium ranged from 90.17-94.45%. Notably, the TDS, the most
      difficult to deal with, were reduced by >50% within 20 days by the consortium.
      The novel consortium developed in this study reduced most of the ecologically
      harmful components in the TW to within the permissible limits of discharge in
      about 5 to 15 days of treatment. Thus, both the tested marine strains of
      Chlorella and Phormidium sp. are promising for bioremediating/detoxifying TW and
      adequately improve the water quality for safe discharge into open water bodies,
      in particular when used as a consortium.

PMID- 29053345
TI  - An ecofriendly approach for bioremediation of contaminated water environment:
      Potential contribution of a coastal seaweed community to environmental
      improvement.
AB  - High levels of heavy metals like copper ions in many industrial based effluents
      lead to serious environmental and health problems. Biosorption is a potential
      environmental biotechnology approach for biotreatment of aquatic sites polluted
      with heavy metal ions. Seaweeds have received great attention for their high
      bioremediation potential in recent years. However, the co-application of marine
      macroalgae for removal of heavy metals from wastewater is very limited. Thus, for
      the first time in literature, a coastal seaweed community composed of
      Chaetomorpha sp., Polysiphonia sp., Ulva sp. and Cystoseira sp. species was
      applied to remove copper ions from synthetic aqueous medium in this study. The
      biosorption experiments in batch mode were conducted to examine the effects of
      operating variables including pH, biosorbent amount, metal ion concentration and
      contact time on the biosorption process. The biosorption behavior of biosorbent
      was described by various equilibrium, kinetic and thermodynamic models. The
      biosorption of copper ions was strongly influenced by the operating parameters.
      The results indicated that the equilibrium data of biosorption were best modeled
      by Sips isotherm model. The values of mean free energy of biosorption computed
      from Dubinin-Radushkevich isotherm model and the standard Gibbs free energy
      change indicated a feasible, spontaneous and physical biotreatment system. The
      pseudo-second-order rate equation successfully defined the kinetic behavior of
      copper biosorption. The pore diffusion also played role in the control of
      biosorption process. The maximum copper uptake capacity of biosorbent was found
      to be greater than those of many other biosorbents. The obtained results revealed
      that this novel biosorbent could be a promising material for copper ion
      bioremediation implementations.

PMID- 29053346
TI  - Plant-based diets do not prevent most chronic diseases.

PMID- 29053347
TI  - Phytotoxicity of tin mine waste and accumulation of involved heavy metals in
      common buckwheat (Fagopyrum esculentum Moench).
AB  - Extraction and processing of cassiterite (SnO2) left large tailings with high
      concentrations of tin, tungsten, molybdenum and lithium. Information on the
      phytotoxicity of mine waste is important with regard to ecological hazards.
      Exposure studies help to identify plants useful for the stabilization of waste
      tips and the phytomining of metals. A greenhouse study was performed using a
      dilution series of mine waste and four crops, a halophytic and a metallophytic
      species to derive dose response curves. Based on effective doses for growth
      reductions, sensitivity increased in the following order: maize > common
      buckwheat > quinoa > garden bean. Element analyses in different species and
      compartments of common buckwheat grown in a mixture of standard soil and 25% of
      the mine waste showed that only low levels of the metals were taken up and that
      transfer to seed tissues was negligible. As indicated by soil metal levels prior
      to and after the experiment, only lithium and arsenic proved to be plant
      available and reached high levels in green tissues while seed levels were low.
      The experiment confirmed differences in the uptake of metals with regard to
      elements and species. Common buckwheat is a suited candidate for cultivation on
      metal polluted soils.

PMID- 29053348
TI  - Use of bacterial acc deaminase to increase oil (especially poly aromatic
      hydrocarbons) phytoremediation efficiency for maize (zea mays) seedlings.
AB  - Oil presence in soil, as a stressor, reduces phytoremediation efficiency through
      an increase in the plant stress ethylene. Bacterial 1-aminocyclopropane-1
      carboxylic acid (ACC) deaminase, as a plant stress ethylene reducer, was employed
      to increase oil phytoremediation efficiency. For this purpose, the ability of ACC
      deaminase-producing Pseudomonas strains to grow in oil-polluted culture media and
      withstand various concentrations of oil and also their ability to reduce plant
      stress ethylene and enhance some growth characteristics of maize and finally
      their effects on increasing phytoremediation efficiency of poly aromatic
      hydrocarbons (PAHs) in soil were investigated. Based on the results, of tested
      strains just P9 and P12 were able to perform oil degradation. Increasing oil
      concentration from 0 to 10% augmented these two strains population, 15.7% and
      12.9%, respectively. The maximum increase in maize growth was observed in
      presence of P12 strain. Results of high-performance liquid chromatography (HPLC)
      revealed that PAHs phytoremediation efficiency was higher for inoculated seeds
      than uninoculated. The highest plant growth and PAHs removal percentage (74.9%)
      from oil-polluted soil was observed in maize inoculated with P12. These results
      indicate the significance of ACC deaminase producing bacteria in alleviation of
      plant stress ethylene in oil-polluted soils and increasing phytoremediation
      efficiency of such soils.

PMID- 29053349
TI  - Essential metal and metalloid elements in the Philippi Horticultural area, and
      their uptake into selected vegetable crops.
AB  - This study evaluated Co, Cr, Mn, Ni, Se, Sn and V status in the soils of the PHA,
      as well as the vegetables produced on these soils. We also determined the
      agronomic sources of these elements to the soils in the PHA. Farmyard manures
      applied as fertilizer amendments to the soils in the PHA were found to be the
      major agronomic sources of the metal and metalloid elements. These elements were
      however, retained in significantly higher concentrations in the soils compared to
      the concentrations found in the edible portions of the vegetable crops collected.
      This, in turn, resulted in these vegetables being poor sources of several of the
      essential mineral nutrients. It is therefore suggested that: (1) a wider variety
      of crops are assessed for their mineral nutrient status, (2) to find ways to
      increase the availability of these mineral nutrients and (3), that the
      possibilities of micronutrient and trace element deficiencies be assessed in the
      communities surrounding the PHA.

PMID- 29053350
TI  - Melatonin affects the growth and cadmium accumulation of Malachium aquaticum and
      Galinsoga parviflora.
AB  - Phytoremediation technology has become one of the main techniques for remediating
      soils polluted by heavy metals because it does not damage the environment, but
      heavy metal-tolerant plants have the disadvantages of low biomass and slow
      growth. A pot experiment was conducted to study the effects of melatonin (Mel) on
      growth and cadmium (Cd) accumulation in the Cd accumulator Malachium aquaticum
      and hyperaccumulator Galinsoga parviflora by spraying different concentrations of
      Mel on them. The results showed that shoot biomass, photosynthetic pigment
      content and antioxidant enzyme activity were increased in both species after Mel
      was sprayed on their leaves. Mel reduced the Cd content in shoots of M. aquaticum
      and increased it in those of G. parviflora. In general, Cd accumulation was
      greatest in M. aquaticum when Mel was 200 MUmol L-1 (120.71 MUg plant-1,
      increased by 15.97% than control) and in G. parviflora when Mel was 100 MUmol L-1
      (132.40 MUg plant-1, increased by 68.30% than control). Our results suggest it is
      feasible to improve the remediation efficiency of lightly Cd-contaminated soil by
      spraying G. parviflora with100 MUmol L-1 Mel.

PMID- 29053351
TI  - Cadmium accumulation and main rhizosphere characteristics of seven French
      marigold (Tagetes patula L.) cultivars.
AB  - The study was conducted to determine Cd accumulation and Cd fraction in the
      rhizosphere soil of seven Tagetes patula cultivars (Little Hero Orange, Durango
      Yellow, Janie Yellow Bright, Lucifer Yellow, Hero Flame, Hongyun Red, Konghuang
      Yellow). T. patula cultivars showed strong tolerance and accumulation to Cd. The
      highest Cd concentration (273.77 mg kg-1) in shoots was observed in Little Hero
      Orange when treated with Cd100. For most cultivars, Cd treatments significantly
      affected rhizosphere pH values, but had a slight effect on dissolved organic
      carbon (DOC). pH were negatively correlated with Cd accumulation and Cd
      percentages in the exchangeable fraction in the rhizosphere soil of Little Hero
      Orange, Durango Yellow, and Konghuang Yellow. No significant correlation was
      observed between DOC, Cd accumulation and Cd percentage in the exchangeable
      fraction in the rhizosphere soil, except for Konghuang Yellow. The results
      suggested that pH might be related to Cd bioavailability and their uptake by T.
      patula. Among seven cultivars, Little Hero Orange showed the greatest pH
      decrease, highest shoot Cd accumulation and Cd percentage in the exchangeable
      fraction, suggesting the difference in pH responses to Cd levels among T. patula
      might be responsible for their different ability of Cd activation.

PMID- 29053352
TI  - Bioaccumulation and rhizofiltration potential of Pistia stratiotes L. for
      mitigating water pollution in the Egyptian wetlands.
AB  - The bioaccumulation and rhizofiltration potential of P. stratiotes for heavy
      metals were investigated to mitigate water pollution in the Egyptian wetlands.
      Plant and water samples were collected monthly through nine quadrats equally
      distributed along three sites at Al-Sero drain in Giza Province. The annual mean
      of the shoot biomass was 10 times that of the root. The concentrations of shoot
      heavy metals fell in the order: Fe < Mn < Cr < Pb < Cu < Zn < Ni < Co < Cd, while
      that of the roots were: Fe < Mn < Cr < Pb < Zn < Ni < Co < Cu < Cd. The bio
      concentration factor (BCF) of most investigated heavy metals, except Cr and Pb,
      was greater than 1000, while the translocation factor (TF) of most investigated
      metals, except Pb and Cu, did not exceed one. The rhizofiltration potential (RP)
      of heavy metals was higher than 1000 for Fe, and 100 for Cr, Pb and Cu.
      Significant positive correlations between Fe and Cu in water with those in plant
      roots and leaves, respectively were recorded, which, in addition to the high BCF
      and RP, indicate the potential use of P. stratiotes in mitigating these toxic
      metals.

PMID- 29053353
TI  - Effect of two biodegradable chelates on metals uptake, translocation and
      biochemical changes of Lantana Camara growing in fly ash amended soil.
AB  - The present work had two purposes firstly to evaluate the potential of Lantana
      Camara for phytoextraction of heavy metals from fly ash amended soil and to
      assess the suitability of a proper biodegradable chelating agent for chelate
      assisted phytoextraction. Plants were grown in manure mixed soil amended with
      various concentration of fly ash. Two biodegradable chelating agents were added
      (EDDS and MGDA) in the same dose separately before maturation stage. Sampling was
      done at different growing stages. The plant took up metal in different plant
      parts in the following order: for Cu, and Zn leaf >root >stem, for Cr and Mn
      leaf>stem >root, for Ni root >leaf>stem and for Pb root~leaf>stem respectively.
      For Cu, Zn, Cr and Mn Lantana camara acted as phytoextractor. Translocation
      factor and bioaccumulation coefficient was>1 signifying enrichment and
      translocation of metals in the plant. Morphological studies showed no toxicity
      symptom in the plant. Among biochemical parameters protein and nitrate reductase
      activity decreased, whereas, chlorophyll and peroxidise activity increased with
      the growth stages. Finally, it was evident from the results that Lantana Camara
      can be used as efficient phytoextractor of metals, with proper harvesting cycle
      and both chelate were proved as effective chelators for phytoextraction of
      metals.

PMID- 29053354
TI  - Articulated Medicine: Pan American Health Organization Reengages Traditional and
      Complementary Medicine Efforts.

PMID- 29053355
TI  - Fatal Attraction? Intraguild Facilitation and Suppression among Predators.
AB  - Competition and suppression are recognized as dominant forces that structure
      predator communities. Facilitation via carrion provisioning, however, is a
      ubiquitous interaction among predators that could offset the strength of
      suppression. Understanding the relative importance of these positive and negative
      interactions is necessary to anticipate community-wide responses to apex predator
      declines and recoveries worldwide. Using state-sponsored wolf (Canis lupus)
      control in Alaska as a quasi experiment, we conducted snow track surveys of apex,
      meso-, and small predators to test for evidence of carnivore cascades (e.g.,
      mesopredator release). We analyzed survey data using an integrative occupancy and
      structural equation modeling framework to quantify the strengths of hypothesized
      interaction pathways, and we evaluated fine-scale spatiotemporal responses of
      nonapex predators to wolf activity clusters identified from radio-collar data.
      Contrary to the carnivore cascade hypothesis, both meso- and small predator
      occupancy patterns indicated guild-wide, negative responses of nonapex predators
      to wolf abundance variations at the landscape scale. At the local scale, however,
      we observed a near guild-wide, positive response of nonapex predators to
      localized wolf activity. Local-scale association with apex predators due to
      scavenging could lead to landscape patterns of mesopredator suppression,
      suggesting a key link between occupancy patterns and the structure of predator
      communities at different spatial scales.

PMID- 29053356
TI  - The Evolution of Clutch Size in Hosts of Avian Brood Parasites.
AB  - Coevolution with avian brood parasites shapes a range of traits in their hosts,
      including morphology, behavior, and breeding systems. Here we explore whether
      brood parasitism is also associated with the evolution of host clutch size.
      Several studies have proposed that hosts of highly virulent parasites could
      decrease the costs of parasitism by evolving a smaller clutch size, because hosts
      with smaller clutches will lose fewer progeny when their clutch is parasitized.
      We describe a model of the evolution of clutch size, which challenges this logic
      and shows instead that an increase in clutch size (or no change) should evolve in
      hosts. We test this prediction using a broad-scale comparative analysis to ask
      whether there are differences in clutch size within hosts and between hosts and
      nonhosts. Consistent with our model, this analysis revealed that host species do
      not have smaller clutches and that hosts that incur larger costs from raising a
      parasite lay larger clutches. We suggest that brood parasitism might be an
      influential factor in clutch-size evolution and could potentially select for the
      evolution of larger clutches in host species.

PMID- 29053357
TI  - The Roles of Sexual and Viability Selection in the Evolution of Incomplete
      Reproductive Isolation: From Allopatry to Sympatry.
AB  - In recent years, theoretical models have introduced the concept that ongoing
      hybridization between "good" species can occur because incomplete reproductive
      isolation can be a selected optimum. They furthermore show that positive
      frequency-dependent sexual selection, which is naturally generated by some of the
      underlying processes that lead to assortative mating, plays a key role in the
      evolution of incomplete reproductive isolation. This occurs, however, through
      different mechanisms in sympatric versus allopatric scenarios. We investigate the
      evolution of incomplete reproductive isolation by sexual selection in scenarios
      ranging from sympatry to allopatry, to examine how these mechanisms interact. We
      consider an ecological scenario in which there are two habitats used during
      foraging and individuals can breed either within a habitat or in a common mating
      pool. We find that when trait divergence is maintained, sexual selection drives
      the evolution of choosiness in opposite ways in the common mating pool versus
      within each habitat. Specifically, strong choosiness is favored in the common
      mating pool, whereas intermediate choosiness is favored within habitat; the
      interaction of these forces determines whether intermediate reproductive
      isolation ultimately evolves in the system. We further find cases where the
      evolution of stronger choosiness occurs but leads to the loss of divergence.
      Overall, our study shows that contrasting forces on the evolution of reproductive
      isolation can occur in different mating areas, and we propose a new avenue for
      understanding the diversity in levels of reproductive isolation within and across
      species.

PMID- 29053358
TI  - Bioinvasion Triggers Rapid Evolution of Life Histories in Freshwater Snails.
AB  - Biological invasions offer interesting situations for observing how novel
      interactions between closely related, formerly allopatric species may trigger
      phenotypic evolution in situ. Assuming that successful invaders are usually
      filtered to be competitively dominant, invasive and native species may follow
      different trajectories. Natives may evolve traits that minimize the negative
      impact of competition, while trait shifts in invasives should mostly reflect
      expansion dynamics, through selection for colonization ability and transiently
      enhanced mutation load at the colonization front. These ideas were tested through
      a large-scale common-garden experiment measuring life-history traits in two
      closely related snail species, one invasive and one native, co-occurring in a
      network of freshwater ponds in Guadeloupe. We looked for evidence of recent
      evolution by comparing uninvaded or recently invaded sites with long-invaded
      ones. The native species adopted a life history favoring rapid population growth
      (i.e., increased fecundity, earlier reproduction, and increased juvenile
      survival) that may increase its prospects of coexistence with the more
      competitive invader. We discuss why these effects are more likely to result from
      genetic change than from maternal effects. The invader exhibited slightly
      decreased overall performances in recently colonized sites, consistent with a
      moderate expansion load resulting from local founder effects. Our study
      highlights a rare example of rapid life-history evolution following invasion.

PMID- 29053359
TI  - Cannibalism and Intraguild Predation Community Dynamics: Coexistence, Competitive
      Exclusion, and the Loss of Alternative Stable States.
AB  - Predators often exert strong top-down regulation of prey, but in many systems,
      juvenile predators must compete with their future prey for a shared resource. In
      such life-history intraguild predation (LHIGP) systems, prey can therefore also
      regulate the recruitment and thus population dynamics of their predator via
      competition. Theory predicts that such stage-structured systems exhibit a wide
      range of dynamics, including alternative stable states. Here we show that
      cannibalism is an exceedingly common interaction within natural LHIGP systems
      that determines what coexistence states are possible. Using a modeling approach
      that simulates a range of ontogenetic diet shift scenarios along a productivity
      gradient, we demonstrate that only if the predator is competitively dominant can
      cannibalism promote coexistence by allowing prey to persist. If the prey is
      competitively dominant, cannibalism instead results in competitive exclusion of
      the predator and the loss of potential alternative stable states. Further,
      predator exclusion occurs at low cannibalistic preference relative to empirical
      estimates and is consistent across LHIGP systems in which the predator undergoes
      a complete diet shift or diet broadening over ontogeny. Given that prey is
      frequently competitively dominant in natural systems, our results demonstrate
      that even weak cannibalism can inhibit predator persistence, prompting
      exploration of mechanisms that reconcile theory with the common occurrence of
      such interactions in nature.

PMID- 29053306
TI  - GW170814: A Three-Detector Observation of Gravitational Waves from a Binary Black
      Hole Coalescence.
AB  - On August 14, 2017 at 10?30:43 UTC, the Advanced Virgo detector and the two
      Advanced LIGO detectors coherently observed a transient gravitational-wave signal
      produced by the coalescence of two stellar mass black holes, with a false-alarm
      rate of ?1 in 27 000 years. The signal was observed with a three-detector network
      matched-filter signal-to-noise ratio of 18. The inferred masses of the initial
      black holes are 30.5_{-3.0}^{+5.7}M_{?} and 25.3_{-4.2}^{+2.8}M_{?} (at the 90%
      credible level). The luminosity distance of the source is 540_{-210}^{+130}  Mpc,
      corresponding to a redshift of z=0.11_{-0.04}^{+0.03}. A network of three
      detectors improves the sky localization of the source, reducing the area of the
      90% credible region from 1160   deg^{2} using only the two LIGO detectors to 60 
      deg^{2} using all three detectors. For the first time, we can test the nature of
      gravitational-wave polarizations from the antenna response of the LIGO-Virgo
      network, thus enabling a new class of phenomenological tests of gravity.

PMID- 29053360
TI  - Habitat Association Predicts Genetic Diversity and Population Divergence in
      Amazonian Birds.
AB  - The ecological traits of organisms may predict their genetic diversity and
      population genetic structure and mediate the action of evolutionary processes
      important for speciation and adaptation. Making these ecological-evolutionary
      links is difficult because it requires comparable genetic estimates from many
      species with differing ecologies. In Amazonian birds, habitat association is an
      important component of ecological diversity. Here, we examine the link between
      habitat association and genetic parameters using 20 pairs of closely related
      Amazonian bird species in which one member of the pair occurs primarily in forest
      edge and floodplains and the other occurs in upland forest interior. We use
      standardized geographic sampling and data from 2,416 genomic markers to estimate
      genetic diversity, population genetic structure, and statistics reflecting
      demographic and evolutionary processes. We find that species of upland forest
      have greater genetic diversity and divergence across the landscape as well as
      signatures of older histories and less gene flow than floodplain species. Our
      results reveal that species ecology in the form of habitat association is an
      important predictor of genetic diversity and population divergence and suggest
      that differences in diversity between floodplain and upland avifaunas in the
      Amazon may be driven by differences in the demographic and evolutionary processes
      at work in the two habitats.

PMID- 29053361
TI  - Artificial Selection to Increase the Phenotypic Variance in gmax Fails.
AB  - Stabilizing selection is important in evolutionary theories of the maintenance of
      genetic variance and has been invoked as the key process determining
      macroevolutionary patterns of trait evolution. However, manipulative evidence for
      the extent of stabilizing selection, particularly on multivariate traits, is
      lacking. We used artificial disruptive selection in Drosophila serrata as a tool
      to determine the relative strength of stabilizing selection experienced by
      multivariate trait combinations with contrasting levels of genetic and mutational
      variance. Contrary to expectation, when disruptive selection was applied to the
      major axis of standing genetic variance, gmax, we observed a significant and
      repeatable decrease in its phenotypic variance. In contrast, the multivariate
      trait combination predicted to be under strong stabilizing selection showed a
      significant and repeatable increase in its phenotypic variance. Correlated
      responses were observed in all selection treatments, and viability selection
      operating on extreme phenotypes of traits genetically correlated with those
      directly selected on limited our ability to increase their phenotypic range. Our
      manipulation revealed that multivariate trait combinations were subject to
      stabilizing selection; however, we did not observe a direct relationship between
      the strength of stabilizing selection and the levels of standing genetic variance
      in multivariate trait combinations. Contrasting patterns of allele frequencies
      underlying traits with high versus low levels of standing genetic variance may be
      implicated in determining the response to artificial selection in multivariate
      trait combinations.

PMID- 29053362
TI  - Frontispiece.

PMID- 29053363
TI  - Toward a Periodic Table of Niches, or Exploring the Lizard Niche Hypervolume.
AB  - Widespread niche convergence suggests that species can be organized according to
      functional trait combinations to create a framework analogous to a periodic
      table. We compiled ecological data for lizards to examine patterns of global and
      regional niche diversification, and we used multivariate statistical approaches
      to develop the beginnings for a periodic table of niches. Data (50+ variables)
      for five major niche dimensions (habitat, diet, life history, metabolism,
      defense) were compiled for 134 species of lizards representing 24 of the 38
      extant families. Principal coordinates analyses were performed on niche
      dimensional data sets, and species scores for the first three axes were used as
      input for a principal components analysis to ordinate species in continuous niche
      space and for a regression tree analysis to separate species into discrete niche
      categories. Three-dimensional models facilitate exploration of species positions
      in relation to major gradients within the niche hypervolume. The first gradient
      loads on body size, foraging mode, and clutch size. The second was influenced by
      metabolism and terrestrial versus arboreal microhabitat. The third was influenced
      by activity time, life history, and diet. Natural dichotomies are activity time,
      foraging mode, parity mode, and habitat. Regression tree analysis identified 103
      cases of extreme niche conservatism within clades and 100 convergences between
      clades. Extending this approach to other taxa should lead to a wider
      understanding of niche evolution.

PMID- 29053364
TI  - Climate Effects on Growth, Body Condition, and Survival Depend on the Genetic
      Characteristics of the Population.
AB  - Climatic change is expected to affect individual life histories and population
      dynamics, potentially increasing vulnerability to extinction. The importance of
      genetic diversity has been highlighted for adaptation and population persistence.
      However, whether responses of life-history traits to a given environmental
      condition depend on the genetic characteristics of a population remains elusive.
      Here we tested this hypothesis in the lizard Zootoca vivipara by simultaneously
      manipulating habitat humidity, a major climatic predictor of Zootoca's
      distribution, and adult male color morph frequency, a trait with genome-wide
      linkage. Interactive effects of humidity and morph frequency had immediate
      effects on growth and body condition of juveniles and yearlings, as well as on
      adult survival, and delayed effects on offspring size. In yearlings, higher
      humidity led to larger female body size and lower humidity led to higher male
      compared to female survival. In juveniles and yearlings, some treatment effects
      were compensated over time. The results show that individual responses to
      environmental conditions depend on the population's color morph frequency, age
      class, and sex and that these affect intra- and inter-age class competition.
      Moreover, humidity affected the competitive environment rather than imposing
      trait-based selection on specific color morphs. This indicates that species'
      responses to changing environments (e.g., to climate change) are highly complex
      and difficult to accurately reconstruct and predict without information on the
      genetic characteristics and demographic structure of populations.

PMID- 29053365
TI  - Hollow Internodes Permit a Neotropical Understory Plant to Shelter Multiple
      Mutualistic Ant Species, Obtaining Protection and Nutrient Provisioning
      (Myrmecotrophy).
AB  - The Neotropical understory plant Tachia guianensis (Gentianaceae)-known to
      shelter the colonies of several ant species in its hollow trunks and branches
      does not provide them with food rewards (e.g., extrafloral nectar). We tested
      whether these ants are opportunistic nesters or whether mutualistic relationships
      exist as for myrmecophytes or plants sheltering ant colonies in specialized
      hollow structures in exchange for protection from enemies and/or nutrient
      provisioning (myrmecotrophy). We noted 37 ant species sheltering inside T.
      guianensis internodes, three of them accounting for 43.5% of the cases. They
      protect their host plants from leaf-cutting ant defoliation and termite damage
      because individuals devoid of associated ants suffered significantly more
      attacks. Using the stable isotope 15N, we experimentally showed that the tested
      ant species furnish their host plants with nutrients. Therefore, a mutualism
      exists. However, because it is associated with numerous ant species, T.
      guianensis can be considered a nonspecialized myrmecophyte.

PMID- 29053366
TI  - Heavy metal (Pb) accumulation in metallophytes as influenced by the variations in
      rhizospheric and non-rhizospheric soils physico-chemical characteristics.
AB  - Activities at root-soil interface determine the solubility and uptake of metals
      by plants. Metal accumulation in plant species (Imperata cylindrical, Cynodon
      dactylon, Eleucine indica, Gomphrena celosoides, Sporobolus pyramidalis,
      Chromolaena odorata and Rhynchospora corymbosa) growing on Pb contaminated site
      as influenced by variations in physico-chemical characteristics, dissolved
      organic matter (DOM), Pb fractionation and different functional groups (using
      Fourier Transmittance Infra-red) of rhizospheric and non-rhizospheric soils was
      assessed. The electrical conductivity (2660-5520 us) and Pb concentrations
      (51390.0-64080.0 mg/kg) were more in non-rhizospheric than rhizospheric soils
      having 276 us to 3160 us EC and 3289.0 to 44850.0 mg/kg Pb. More nutrients, DOM
      and carbohydrates functional groups (C-O; 1100 -1000 and O-H; 3700-3600) were
      found in rhizospheric compared to non-rhizospheric soils. The pH was slightly
      acidic (5.0-5.54) and E. indica with the lowest pH (5.0) accumulated highest Pb
      concentrations in shoot (8030 mg/kg) and root (16380 mg/kg) while C. odorata with
      highest values of pH, P, Ca and Mg in rhizospheric soil accumulated the least
      (root; 331.6 and shoot: 209.0 mg/kg). Pb was more in organic and residual
      fractions of rhizospheric and non-rhizospheric soils respectively. Reduction in
      pH, EC coupled with nutrients and DOM availability increased Pb uptake by plants.

PMID- 29053367
TI  - Availability and zinc accumulation in forage grasses grown in contaminated soil.
AB  - Zinc is an important micronutrient to plant growth, but when present in large
      quantities it can become a toxic element to plants. This study was aimed to
      evaluate the growth, concentration, accumulation and availability of Zn to forage
      grasses (Megathyrsus maximus cvs. Aruana and Tanzania, Urochloa brizantha cvs.
      Xaraes and Marandu and Urochloa decumbens cv. Basilisk) cultivated in Zn
      contaminated soils. The experiments were conducted under greenhouse conditions
      over a 90-day evaluation period, and Zn rates were 0, 100, 300 and 900 mg kg-1 of
      soil. The Zn rates in soil caused growth reduction in all evaluated forage
      grasses. The cultivar Aruana was generally more tolerant to Zn, while the Marandu
      was generally more susceptible to the addition of Zn. The cultivar Aruana proved
      to be superior to others due to its higher growth and higher critical level
      toxicity of Zn. None of the forage grasses evaluated can be considered a Zn
      hyperaccumulator. The extraction order was DTPA at pH 7.3 < Mehlich-1 < USEPA
      3051 < USEPA 3052 in the soil independent of forage grasses cultivation. The
      USEPA 3051 extractor was similar to Mehlich-1 in predicting the availability of
      Zn in soil.

PMID- 29053368
TI  - Phytostabilization potential of ornamental plants grown in soil contaminated with
      cadmium.
AB  - In a greenhouse experiment, five ornamental plants, Osmanthus fragrans (OF),
      Ligustrum vicaryi L. (LV), Cinnamomum camphora (CC), Loropetalum chinense var.
      rubrum (LC), and Euonymus japonicas cv. Aureo-mar (EJ), were studied for the
      ability to phytostabilization for Cd-contaminated soil. The results showed that
      these five ornamental plants can grow normally when the soil Cd content is less
      than 24.6 mg.kg-1. Cd was mainly deposited in the roots of OF, LV, LC and EJ
      which have grown in Cd-contaminated soils, and the maximum Cd contents reached
      15.76, 19.09, 20.59 and 32.91 mg.kg-1, respectively. For CC, Cd was mainly
      distributed in the shoots and the maximum Cd content in stems and leaves were
      12.5 and 10.71 mg.kg-1, however, the total amount of Cd in stems and leaves was
      similar with the other ornamental plants. The enzymatic activities in Cd
      contaminated soil were benefited from the five tested ornamental plants
      remediation. Soil urease and sucrase activities were improved, while
      dehydrogenase activity was depressed. Meanwhile, the soil microbial community was
      slightly influenced when soil Cd content is less than 24.6 mg.kg-1 under five
      ornamental plants remediation. The results further suggested that ornamental
      plants could be promising candidates for phytostabilization of Cd-contaminated
      soil.

PMID- 29053369
TI  - Effects of Message Framing on Influenza Vaccination: Understanding the Role of
      Risk Disclosure, Perceived Vaccine Efficacy, and Felt Ambivalence.
AB  - The current study examined the effects of framing in promotional health messages
      on intention to vaccinate against seasonal influenza virus. The findings of an
      experimental study (N = 86) indicated that exposure to both benefits and side
      effects of vaccination (gain-framed with risk disclosure message) led to lower
      intention to receive the flu vaccine. This relationship was mediated by both
      perceived vaccine efficacy and felt ambivalence in a serial order, revealing the
      underlying psychological mechanisms important for understanding health-related
      behaviors. Theoretical implications of constructing sub-framed messages are
      discussed and the concept of second-order framing is introduced.

PMID- 29053370
TI  - Cross-Contamination and Biofilm Formation by Salmonella enterica Serovar
      Enteritidis on Various Cutting Boards.
AB  - Cross-contamination is one of the main factors related to foodborne outbreaks.
      This study aimed to analyze the cross-contamination process of Salmonella
      enterica serovar Enteritidis from poultry to cucumbers, on various cutting board
      surfaces (plastic, wood, and glass) before and after washing and in the presence
      and absence of biofilm. Thus, 10 strains of Salmonella Enteritidis were used to
      test cross-contamination from poultry to the cutting boards and from thereon to
      cucumbers. Moreover, these strains were evaluated as to their capacity to form
      biofilm on hydrophobic (wood and plastic) and hydrophilic materials (glass). We
      recovered the 10 isolates from all unwashed boards and from all cucumbers that
      had contacted them. After washing, the recovery ranged from 10% to 100%,
      depending on the board material. In the presence of biofilm, the recovery of
      salmonellae was 100%, even after washing. Biofilm formation occurred more on wood
      (60%) and plastic (40%) than glass (10%) boards, demonstrating that bacteria
      adhered more to a hydrophobic material. It was concluded that the cutting boards
      represent a critical point in cross-contamination, particularly in the presence
      of biofilm. Salmonella Enteritidis was able to form a biofilm on these three
      types of cutting boards but glass showed the least formation.

PMID- 29053371
TI  - Phytoremediation Capabilities of Spirodela polyrhiza, Salvinia molesta and Lemna
      sp. in Synthetic Wastewater: A Comparative Study.
AB  - Macrophytes have been used to mitigate eutrophication and upgrade effluent
      quality via their nutrient removal capability. However, the available data are
      influenced by factors such as microbial activities, weather, and wastewater
      quality, making comparison between nutrient removal performance of different
      macrophytes almost impossible. In this study, phytoremediation by Spirodela
      polyrhiza, Salvinia molesta and Lemna sp. were carried out axenically in
      synthetic wastewater under controlled condition to precisely evaluate nutrient
      removal efficiency of NO3--N, PO43-, NH3-N, COD and pH in the water sample. The
      results showed that ammonia removal was rapid, significant for S. polyrhiza and
      Lemna sp., with efficiency of 60% and 41% respectively within 2 days. S.
      polyrhiza was capable of reducing 30% of the nitrate. Lemna sp. achieved the
      highest phosphate reduction of 86% at day 12 to mere 1.07 mg/L PO43--P.
      Correlation was found between COD and TC, suggesting the release of organic
      substances by macrophytes into the medium. All the macrophytes showed biomass
      increment. S. polyrhiza outperformed other macrophytes in nutrient removal
      despite lower biomass production. The acquired nutrient removal profiles can
      serve as a guideline for the selection of suitable macrophytes in wastewater
      treatment and to evaluate microbial activity in non-aseptic phytoremediation
      system.

PMID- 29053372
TI  - The Importance of Adolescents' Sexually Outgoing Self-Concept: Differential Roles
      of Self- and Other-Generated Sexy Self-Presentations in Social Media.
AB  - The present study investigated the relationships between (exposure to) sexy self
      presentations on social network sites (SNSs) and adolescents' sexual self-concept
      over time. Results from a three-wave panel study among 1,288 Dutch adolescents
      (aged 13-17 years) showed that more frequent engagement in sexy self
      presentation, rather than exposure to sexy self-presentations of others, on SNSs
      positively predicted the importance of being sexually outgoing (e.g., sexy,
      seductive, and wild) in adolescents' self-concept 6 months later.

PMID- 29053373
TI  - Receipt and Perceived Helpfulness of Mental Illness Information: Findings from
      the Australian National Survey of Mental Health and Wellbeing.
AB  - The distribution of mental illness information is a crucial element of mental
      health promotion initiatives. We assessed the receipt and perceived helpfulness
      of such information in Australia. Data from the Australian National Survey of
      Mental Health and Wellbeing indicated that, during the year prior to the survey,
      33.7% of Australians received mental illness information; of these, 51.2% found
      it helpful. Among people with a mental disorder, 46.1% received information; of
      these, 67.4% found it helpful. Non-English speakers and the socially
      disadvantaged were less likely to receive mental illness information. Older and
      less educated respondents were less likely to both receive mental illness
      information and find it helpful. Mental health service users were more likely to
      receive mental illness information perceived as helpful than those who had not
      accessed such services. Better targeted information interventions are required to
      ensure those most likely to benefit receive mental illness-related information.

PMID- 29053374
TI  - Pedestrian crossing behavior, an observational study in the city of Ushuaia,
      Argentina.
AB  - OBJECTIVES: Pedestrian crashes are a critical problem in Latin American
      countries. However, little research has been published about pedestrians and even
      less about their behaviors in a naturalistic context. The objective of the
      present research was to explore risky pedestrian crossing behaviors in traffic
      intersections in an argentine city (Ushuaia). It is focused in different stages
      of the crossing process, traffic code violations, and other potentially risky
      behaviors such as distractions. A high frequency of risky behaviors among
      pedestrians was expected. Moreover, according to previous findings, it was
      hypothesized that men and younger pedestrians would show riskier behaviors.
      METHODS: Participants were 802 pedestrians (53.9% females) observed at several
      intersections (with and without traffic lights) in the city of Ushuaia. Behaviors
      were codified following a standardized observation protocol. Observers documented
      information on behavior previous to, during, and after crossing. Gender and age
      were also registered. Data were gathered through video recording. Frequency
      analyses of observed behaviors were conducted for the total sample, as well as by
      gender and by age group. A general crossing risk index was calculated to
      facilitate comparisons between the genders and age groups. We conducted an
      analysis of variance to evaluate gender and age differences for this index.
      RESULTS: A high proportion of risky behaviors were observed among pedestrians.
      The majority of pedestrian waited in the street (as opposed to on the sidewalk)
      before crossing, did not comply with traffic lights, or crossed outside the
      crosswalk. A large number of pedestrians were distracted while crossing. Men
      presented higher scores on risky behaviors than women. No differences were
      observed by age group. CONCLUSIONS: The high level of risk behaviors during the
      different stages of street crossing is worrisome and reinforces the idea that
      pedestrians are responsible for many of the conflicts with motorists. Many of the
      risky behaviors seem to be associated with gender, which is in line with the
      previous literature showing more risk behaviors among men than among women. No
      differences were found for age group. Findings are interpreted considering some
      features of the Argentine road culture.

PMID- 29053375
TI  - The Structure of Challenging Parenting Behavior and Associations With Anxiety in
      Dutch and Australian Children.
AB  - Challenging parenting behavior (CPB), a novel construct involving active physical
      and verbal behaviors that encourage children to push their limits, has been
      identified as a potential buffer against child anxiety. This study aimed to (a)
      evaluate the measurement invariance of the Challenging Parenting Behavior
      Questionnaire (CPBQ4-6) across Dutch and Australian mothers and fathers of
      preschoolers, (b) examine differences in levels of CPB across mothers and fathers
      and across countries, and (c) examine whether parents' CPB predicts less child
      anxiety symptoms and disorders. Participants were 312 families-146 Dutch and 166
      Australian-with their 3- to 4-year-old child (55.8% girls). Fathers' and mothers'
      CPB was measured using the CPBQ4-6, and child anxiety symptoms and presence of
      anxiety disorders were assessed using maternal reports. Multigroup confirmatory
      factor analyses revealed equivalence of factor structure and factor loadings (all
      significant) of the CPBQ4-6 across mothers and fathers and across countries.
      Evidence of partial scalar invariance indicated that the groups differed on some
      subscales of the CPBQ4-6. Australian mothers scored lower on the CPB factor than
      Australian fathers and Dutch parents. Structural equation models showed that CPB
      predicted fewer child anxiety symptoms and anxiety disorders for all groups. The
      study confirms that the CPBQ4-6 is appropriate for use with Dutch and Australian
      parents of preschool-age children and identifies CPB as a multifaceted and
      coherent construct. The negative relations between CPB and child anxiety suggest
      that CPB has a protective role in childhood anxiety and is important to examine
      in future research and interventions.

PMID- 29053376
TI  - Eighth International Congress of Peer Review and Scientific Publication:
      Enhancing the Quality and Credibility of Science, Chicago, Illinois, September 10
      12, 2017.

PMID- 29053378
TI  - Genetic diversity of Jiangsu native chicken breeds assessed with the
      mitochondrial DNA D-loop region.
AB  - 1. The objective of this study was to determine the origin and evolution of
      chickens from 5 native breeds that are traditionally raised in Jiangsu Province.
      2. To address this question, the complete mitochondrial DNA D-loop sequence of
      149 chickens from 5 native breeds of Jiangsu Province was analysed. 3. Sequence
      read lengths of the native breeds were 1231 to 1232 bp, with a single-base
      deletion from the 859 bp site in the 1231 bp haplotype. A total of 33 variable
      sites that defined 19 haplotypes were identified. The average haplotype diversity
      and nucleotide diversity were 0.862 +/- 0.017 and 0.00591 +/- 0.00135. 4.
      Phylogenetic analysis showed that genetic structure of the mtDNA haplotypes of
      Jiangsu chickens are distributed across 5 clades (haplogroups): Clades A, B, C,
      D, and E. However, most of the individuals characterised in this study belonged
      to clades A and B. 5. The results of this study indicate that Jiangsu chicken
      populations have relatively low nucleotide and haplotype diversity and likely
      share 5 common maternal lineages.

PMID- 29053377
TI  - Substance use among bi/multiracial youth in the United States: Profiles of
      psychosocial risk and protection.
AB  - BACKGROUND: Bi/multiracial youth face higher risk of engaging in substance use
      than most monoracial youth. OBJECTIVES: This study contrasts the prevalence of
      substance use among bi/multiracial youth with that of youth from other
      racial/ethnic groups, and identifies distinct profiles of bi/multiracial youth by
      examining their substance use risk. METHODS: Using data from the National Survey
      on Drug Use and Health (collected between 2002 and 2014), we analyze data for
      9,339 bi/multiracial youth ages 12-17 living in the United States. Analyses use
      multinomial regression and latent class analysis. RESULTS: With few exceptions,
      bi/multiracial youth in general report higher levels of tobacco, alcohol,
      marijuana, and other illicit drug use compared to other youth of color.
      Bi/multiracial youth also report higher levels of marijuana use compared to non
      Hispanic white adolescents. However, latent class modeling also revealed that a
      majority (54%) of bi/multiracial youth experience high levels of psychosocial
      protection (i.e., strong antidrug views and elevated parental engagement) and low
      levels of psychosocial risk (i.e., low peer substance use, school-related
      problems, and social-environmental risk), and report very low levels of substance
      use. Substance use was found to be particularly elevated among a minority of
      bi/multiracial youth (28%) reporting elevated psychosocial risk and low levels of
      protection. Bi/multiracial youth characterized by both elevated psychosocial risk
      and elevated psychosocial protection (22%) reported significantly elevated
      substance use as well. CONCLUSIONS: While bi/multiracial youth in general exhibit
      elevated levels of substance use, substantial heterogeneity exists among this
      rapidly-growing demographic.

PMID- 29053379
TI  - The Impact of Cost Conversations on the Patient-Physician Relationship.
AB  - Previous research has suggested that fear of harm to the patient-physician
      relationship is an important barrier to conversations about cost of care.
      However, few experimental studies have investigated the effects of cost of care
      conversations on the patient-physician relationship, particularly from the
      patient's perspective. In the current research, we take an experimental approach
      to investigate patients' attitudes and preferences for a hypothetical physician
      who discusses cost versus one who does not. Across three studies, using data from
      both the general population and cancer patients, we find that people prefer a
      hypothetical physician who discusses cost over one who does not (Pilot Study,
      Studies 1 and 2). In addition, we find that people use cost information to inform
      their hypothetical treatment decisions without changing their attitudes toward
      the physician who includes this information (Study 1). Finally, we examine how
      and when cost information compares to more traditional medical information (e.g.,
      side effects; Study 2). We discuss the implications of this research for cost
      communications and the patient-physician relationship, highlighting that cost
      conversations may not be as harmful as previously thought.

PMID- 29053380
TI  - Indirect Effects of Social Skills on Health Through Stress and Loneliness.
AB  - The social skills deficit vulnerability model predicts that people with
      inadequate social skills are at risk for a range of psychosocial problems,
      especially when confronted with stress. People with poor social skills often
      experience stress and loneliness and these two constructs were tested as
      potential pathways by which the poor social skills confer a risk for compromised
      mental and physical health. An online survey was completed by 775 adults, aged 18
      91. The sample matched national demographics for race/ethnicity and age, among
      those over 18. Structural equation modeling revealed indirect effects of social
      skills on both mental and physical health through both stress and loneliness. The
      models showed that poor social skills were associated with poor mental and
      physical health through elevated stress and increased loneliness. The findings
      reveal that social skills deficits are associated with physical as well as mental
      health problems.

PMID- 29053381
TI  - Adaptive NetworkProfiler for Identifying Cancer Characteristic-Specific Gene
      Regulatory Networks.
AB  - There is currently much discussion about sample (patient)-specific gene
      regulatory network identification, since the efficiently constructed sample
      specific gene networks lead to effective personalized cancer therapy. Although
      statistical approaches have been proposed for inferring gene regulatory networks,
      the methods cannot reveal sample-specific characteristics because the existing
      methods, such as an L1-type regularization, provide averaged results for all
      samples. Thus, we cannot reveal sample-specific characteristics in
      transcriptional regulatory networks. To settle on this issue, the NetworkProfiler
      was proposed based on the kernel-based L1-type regularization. The
      NetworkProfiler imposes a weight on each sample based on the Gaussian kernal
      function for controlling effect of samples on modeling a target sample, where the
      amount of weight depends on similarity of cancer characteristics between samples.
      The method, however, cannot perform gene regulatory network identification well
      for a target sample in a sparse region (i.e., for a target sample, there are only
      a few samples having a similar characteristic of the target sample, where the
      characteristic is considered as a modulator in sample-specific gene network
      construction), since a constant bandwidth in the Gaussian kernel function cannot
      effectively group samples for modeling a target sample in sparse region. The
      cancer characteristics, such as an anti-cancer drug sensitivity, are usually
      nonuniformly distributed, and thus modeling for samples in a sparse region is
      also a crucial issue. We propose a novel kernel-based L1-type regularization
      method based on a modified k-nearest neighbor (KNN)-Gaussian kernel function,
      called an adaptive NetworkProfiler. By using the modified KNN-Gaussian kernel
      function, our method provides robust results against the distribution of
      modulators, and properly groups samples according to a cancer characteristic for
      sample-specific analysis. Furthermore, we propose a sample-specific generalized
      cross-validation for choosing the sample-specific tuning parameters in the kernel
      based L1-type regularization method. Numerical studies demonstrate that the
      proposed adaptive NetworkProfiler effectively performs sample-specific gene
      network construction. We apply the proposed statistical strategy to the publicly
      available Sanger Genomic data analysis, and extract anti-cancer drug sensitivity
      specific gene regulatory networks.

PMID- 29053383
TI  - Online Activity, Offline Sociability, and Life Satisfaction Among Israelis With
      and Without Disabilities.
AB  - The Internet has the power to enrich the lives of persons with and without
      disabilities, and increase independence and subjective well-being. Using path
      analysis, the study examines the role of Internet use, offline social
      participation, and connectedness in explaining life satisfaction among people
      with and without disabilities. Two mediating models have been examined: the first
      hypothesizes that social participation and connectedness are mediating variables
      between online use and life satisfaction; the second posits that the association
      between participation and connectedness to life satisfaction is mediated by
      Internet use. The secondary data utilized measures from the Kessler National
      Organization on Disability, 2000 and 2004-Harris survey on a national sample of
      557 Israelis with disabilities and a parallel sample of 551 people without
      disabilities. Findings indicate that people with disabilities tend to participate
      less and have weaker level of connectedness, and consequently are less satisfied
      with their life, than persons without disabilities. No significant difference has
      been found between the two groups in social and other online activities. In terms
      of the mediating models, the first mediation model has been confirmed for people
      with disabilities-both connectedness and participation serve as mediators between
      online social activity and life satisfaction. Interestingly, among those without
      disabilities, only connectedness has been a mediator in the path between social
      and other online activities and life satisfaction. Findings are discussed is
      respect to future research and rehabilitation practice.

PMID- 29053382
TI  - Benchmarking Treatment Adherence and Therapist Competence in Individual Cognitive
      Behavioral Treatment for Youth Anxiety Disorders.
AB  - Evidence-based treatments (EBTs) for youth are typically developed and
      established through studies in research settings designed to ensure treatment
      integrity, that is, protocol adherence and competence by therapists. An important
      question for implementation science is how well integrity is maintained when
      these EBTs are delivered in community settings. The present study investigated
      whether the integrity achieved by therapists in community settings achieved a
      benchmark set by therapists in a research setting when they delivered the same
      EBT-an individual cognitive-behavioral treatment (ICBT) for youth anxiety.
      Therapists (N = 29; 68.97% White; 13.79% male) provided ICBT to 68 youths (M age
      = 10.60 years, SD = 2.03; 82.35% White; 52.94% male) diagnosed with a principal
      anxiety disorder in research or community settings. Training and supervision
      protocols were the same across settings. Two independent teams of trained coders
      rated 744 sessions using observational instruments designed to assess ICBT
      adherence and competence. Both adherence and competence were higher in the
      research setting. Group differences in competence were consistent across
      treatment, but differences in adherence were most pronounced when treatment
      shifted to exposure, widely viewed as the most critical component of ICBT. When
      using the benchmarks from the research setting, therapists from the community
      settings fell short for indices of adherence and competence. However, given
      differences between therapists and clients, as well as the fact that treatment
      outcomes were similar across settings, our findings raise questions about whether
      it is appropriate to use treatment integrity benchmarks from research settings
      for community.

PMID- 29053384
TI  - Children's Executive Function Attenuate the Link Between Maternal Intrusiveness
      and Internalizing Behaviors at School Entry.
AB  - The goal of this study was to examine the independent and interactive roles of
      harsh-intrusive maternal behaviors and children's executive function in the
      development of internalizing behaviors across the first years of school. A
      diverse sample (58% African American, 42% European American) of 137 children (48%
      female) was followed from kindergarten (age 5 years) through school entry (ages 6
      7 years). At age 5, maternal harsh-intrusive parenting behaviors were rated from
      a mother-child structured play task, and children completed 3 executive function
      tasks that measured inhibitory control, working memory, and attention set
      shifting. Teachers reported on children's internalizing behaviors at ages 5, 6,
      and 7. Harsh-intrusive parenting behaviors at age 5 years were positively related
      to internalizing behaviors in the first years of school, whereas high executive
      function abilities at age 5 years were related to lower internalizing behaviors
      in the first years of school. In addition, executive function buffered the
      association between parenting behaviors and internalizing behaviors such that the
      link between harsh-intrusive parenting and child internalizing behaviors was
      evident only among children with low executive function and not among children
      with high executive function. Interventions that focus on reducing negative
      parenting behaviors and improving children's executive function may prevent
      internalizing behaviors from increasing during times of social and academic
      challenge.

PMID- 29053385
TI  - Full scale horizontal subsurface flow constructed wetlands to treat domestic
      wastewater by Juncus acutus and Cortaderia selloana.
AB  - In the present study, a full scale horizontal subsurface flow constructed wetland
      was designed, constructed and operated to treat domestic wastewater of
      Kizilcaoren village in Samsun city of Turkey. The total surface area of HSFCW was
      divided into equal parts. The effects of Juncus acutus L. and Cortaderia selloana
      (Schult.Schult.f.)Asch.&Graebn. on pollutants removal in HSFCWs were evaluated
      with the meteorological factors. The average removal efficiencies of J. acutus
      and C. selloana were determined as 60.3-57.7% for BOD; 24.2-38.9% for TN; 31.4
      49.8% for OM; 35.4-43.3% for TP; 18.9-27.1% for orthophosphate; 24.4-28.7% for
      NH4-N; 29.5-37.2% for TSS; and 35.3-44.3% for TSM. Two-way ANOVA was applied to
      determine any difference for the removal of all parameters between the plant
      types and months on the mean values of contaminant removal. A correlation matrix
      of all parameters was determined. Subsurface flow constructed wetland was found
      quite efficient for the treatment of domestic wastewater in rural settlements.
      HSFCW is also more economical to install and maintain than a conventional
      wastewater treatment system while enhancing ecosystem services.

PMID- 29053386
TI  - Promoting Health from the Pulpit: A Process Evaluation of HIV Sermons to Reduce
      HIV Stigma and Promote Testing in African American and Latino Churches.
AB  - Embedding health messages into sermons is a potentially valuable strategy to
      address HIV and other health disparities in churches that predominantly serve
      racial and ethnic minorities. This study explores implementation of an HIV sermon
      as part of a multi-component intervention in three churches (Latino Catholic,
      Latino Pentecostal, and African American Baptist) in high HIV prevalence areas of
      Los Angeles County, California. Clergy were given an HIV sermon guide that
      included local public health data, stigma reduction cues, HIV testing messages,
      and a sample sermon. Findings are based on a process evaluation (i.e., reach,
      dose delivered, fidelity, and implementation) and in-depth content analysis to
      explore HIV frames and messages used by clergy. Sermons were audio-recorded,
      transcribed verbatim, and coded using an inductive approach. Complementary data
      were collected through systematic observation. Overall, five clergy delivered
      nine HIV sermons to majority African American or Latino audiences. On average,
      174 congregants were reached per sermon. We found large variation in fidelity to
      communicating key HIV messages from the sermon guide. While promoting HIV testing
      from the pulpit seemed viable and acceptable to all the participating clergy,
      fewer embedded explicit stigma reduction cues. Most spoke about HIV using
      compassionate and non-judgmental terms, however, issue framing varied across
      clergy. Structured training of clergy may be necessary to implement the more
      theoretically driven stigma reduction cues included in the sermon guide. More
      research is needed on the viability and acceptability of embedding specific
      health promotion messages into sermons.

PMID- 29053387
TI  - Facebook False Self-Presentation Behaviors and Negative Mental Health.
AB  - As research examining what constitutes Facebook false self-presentation is
      lacking, the aim of this study was to develop a preliminary inventory of Facebook
      false self-presentation behaviors, as well as identify predictors and possible
      outcomes. Participants (N = 211) completed questions regarding frequency of
      engagement in Facebook false self-presentation behaviors, as well as self-esteem,
      social influences, motivation strategies, well-being, depression, anxiety, and
      stress. Results indicated the presence of two distinct false self-presentation
      behaviors: lying (e.g., untruthful status updates, profile creation) and liking
      behaviors (e.g., liking posts dishonestly), each associated with different
      predictors and outcomes. Results indicated that moral norms significantly
      predicted lying behaviors; and age, self-esteem, group norms, and moral norms
      significantly predicted liking behaviors. Unexpectedly, liking behaviors were
      associated with depression, anxiety, and stress, whereas lying behaviors were
      related to anxiety only. Findings highlight associations between online self
      presentation strategies, in particular liking behaviors, on Facebook and possible
      offline negative mental health.

PMID- 29053388
TI  - Some chemotherapeutics-treated colon cancer cells display a specific phenotype
      being a combination of stem-like and senescent cell features.
AB  - Colorectal cancer (CRC) is the second leading cause of death among cancer
      patients in the Northern countries. CRC can reappear a long time after treatment.
      Recent clinical studies demonstrated that, in response to chemotherapy, cancer
      cells may undergo stress-induced premature senescence (SIPS), which typically
      results in growth arrest. Nonetheless, these senescent cells were reported to
      divide in an atypical manner and thus contribute to cancer re-growth. Therefore,
      we examined if SIPS escape may follow treatment with chemotherapeutics used
      clinically: 5-fluorouracil (5-FU), oxaliplatin (OXA) and irinotecan (IRINO). To
      mimic the therapeutic regimes we exposed human colon cancer HCT116 and SW480
      cells to repeated cycles of drug treatment. The cells treated with 5-FU or IRINO
      exhibited several hallmarks of SIPS: growth arrest, increased size and
      granularity, polyploidization, augmented activity of the SA-beta-galactosidase,
      accumulation of P21 and CYCLIN D1 proteins, and the senescence-associated
      secretory phenotype. Moreover, re-population of the cancer cell cultures was
      delayed upon treatment with the senescence-inducing agents. At the same time, we
      detected a subpopulation of senescent colon cancer cells with features of
      stemness: elevated NANOG expression, exclusion of Hoechst 33342 (typical for side
      population) and increased CD24 expression. Additionally, rare, polyploid cells
      exhibited blastocyst-like morphology and produced progeny. In parallel, majority
      of chemotherapeutics-treated cells underwent mesenchymal to epithelial
      transition, as the percentage of CD44-positve cells was reduced, and levels of E
      cadherin (epithelial marker) were elevated. Our study demonstrates that a
      subpopulation of chemotherapeutics-treated colon cancer cells display a specific
      phenotype being a combination of stem-like and senescent cell features. This may
      contribute to their resistance to chemotherapy and their ability to re-grow
      cancer after completion of therapeutic intervention.

PMID- 29053389
TI  - MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL
      Approach.
AB  - A valuable approach to understand how individual and population genetic
      differences can predispose to disease is to assess the impact of genetic variants
      on cellular functions (e.g., gene expression) of cell and tissue types related to
      pathological states. To understand the genetic basis of nonsyndromic cleft lip
      with or without cleft palate (NSCL/P) susceptibility, a complex and highly
      prevalent congenital malformation, we searched for genetic variants with a
      regulatory role in a disease-related tissue, the lip muscle (orbicularis oris
      muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently
      discarded during routine corrective surgeries on patients with orofacial clefts,
      we derived mesenchymal stem cells and correlated the individual genetic variants
      with gene expression from these cultured cells. Through this strategy, we
      detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and
      selected a few candidates to conduct an association study in a large Brazilian
      cohort (624 patients and 668 controls). This resulted in the discovery of a novel
      susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene,
      where evidence for association was mostly driven by the Native American ancestry
      component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit
      of mitochondrial ribosomes and interacts with MYC, a transcription factor
      required for normal facial morphogenesis. Our study illustrates not only the
      importance of sampling admixed populations but also the relevance of measuring
      the functional effects of genetic variants over gene expression to dissect the
      complexity of disease phenotypes.

PMID- 29053390
TI  - Exploring the teaching and learning of clinical reasoning, risks, and benefits of
      cervical spine manipulation.
AB  - The aim of this study was to examine how risks and benefits of cervical spine
      manipulation (CSM) were framed and discussed in the context of mentorship and
      their impact on the perception of safe practice of CSM in clinical physiotherapy
      settings. A multi-method qualitative approach was employed, including a document
      analysis of established educational guidelines, observations of mentoring
      sessions, and individual face-to-face interviews with five mentees in the process
      of learning CSM, and four mentors with Orthopedic Manual Physical Therapy (OMPT)
      certification. Results demonstrated that participants' clinical decision-making
      processes to perform CSM were primarily oriented to the mitigation of risk.
      Achieving proficiency in the "science" of clinical reasoning and the "art" of
      "feel" related to mastering technical skills were viewed as means to mitigating
      risk and enhancing confidence to use CSM safely in clinical practice. While the
      "art" of technical skill mastery was of high importance to mentees and considered
      important to developing competency in performing CSM, it was discussed as
      distinct from their clinical reasoning processes. Thus, promoting a more balanced
      and integrated use of the "art" and "science" of safe practice for CSM in OMPT
      training may result in greater confidence and judicious use of CSM by
      physiotherapists.

PMID- 29053391
TI  - Drinking Refusal Self-Efficacy and Intended Alcohol Consumption During a Mass
      Attended Youth Event.
AB  - BACKGROUND: Mass-attended youth events represent a substantial public health
      challenge due to high levels of alcohol consumption and corresponding high rates
      of alcohol-related harm. Although previous research has documented the protective
      effect of high drinking refusal self-efficacy (DRSE) on alcohol consumption in
      general, there is a lack of research examining the role of DRSE in reducing
      consumption during mass-attended youth events and the factors associated with
      DRSE in these contexts. OBJECTIVES: This study aimed to identify potentially
      modifiable factors that influence DRSE and drinking intentions to inform
      interventions designed to reduce alcohol-related harm during mass-attended
      events. METHODS: Australian secondary school students (n = 586; 70% female) in
      their final two years of high school completed an online survey assessing their
      alcohol consumption intentions for Schoolies, their perceived degree of DRSE, and
      other individual and environmental factors. Path analysis was used to assess a
      mediational model examining factors associated with DRSE and alcohol consumption
      intentions. RESULTS: DRSE was found to be significantly associated with intended
      alcohol consumption during Schoolies. Specifically, leavers who believed they
      would not be able to refuse others' offers of alcoholic drinks reported
      significantly greater alcohol consumption intentions. Results also revealed that
      DRSE was enhanced in those respondents who believed there would be a variety of
      non-drinking activities and non-alcoholic beverages available to them during
      Schoolies. CONCLUSION: Results suggest the need to increase leavers' confidence
      in their ability to refuse unwanted alcoholic beverages and highlight the
      importance of providing celebration options that do not involve alcohol
      consumption.

PMID- 29053392
TI  - Mental Health-Related Stigma in China.
AB  - OBJECTIVE: The past decade has been marked by a significant increase in
      information on stigma associated with mental disorders, but these findings have
      yet to be applied extensively to mental health services in China. The objective
      of this study was to conduct a narrative review of studies relating to stigma
      toward mental illness in China. METHODS: A critical search of scientific papers
      was conducted in the PubMed, CNKI, and WANFANG databases. The search included
      articles published from January 2001 to April 2016. RESULTS: Forty-two studies
      were evaluated and arranged into the following category groups: general public,
      health professionals, medical students, family members and caregivers, and people
      with mental disorders. CONCLUSION: We identified some results similar to those
      reported in foreign settings. However, some noteworthy findings concerning the
      stigma of health professionals, medical students, and family members towards
      people with mental disorders in China should be the focus of further research.
      Interventions designed to reduce mental health-related stigma may benefit from
      considering cultural influences exhibited by the Chinese population.

PMID- 29053393
TI  - Depression and Alcohol Use in a National Sample of Hispanic Adolescents.
AB  - BACKGROUND: Underage alcohol use and depression remain public health concerns for
      Hispanic adolescents nationwide. OBJECTIVES: The study purpose was to identify
      the profiles of depression among Hispanic adolescents who reported experiencing
      depressive symptoms in their lifetime and classify them into groups based on
      their symptoms. Based on classifications, we examined the relationship between
      past year alcohol use and severity of depressive symptoms while controlling for
      sex and age. METHODS: A secondary analysis of the 2013 NSDUH was conducted among
      Hispanic adolescents from 12 to 17 years of age (n = 585) who reported
      experiencing depressive symptoms. Latent class analysis was used to identify
      latent classes of depressive symptoms among Hispanic adolescents. A zero-inflated
      negative-binomial regression model was used to examine the relationship between
      alcohol use and depressive symptoms. RESULTS: "High depressive" and "moderate
      depressive" classes were formed. The items that highly differentiated among the
      groups were felt worthless nearly every day, others noticed they were restless or
      lethargic, and had changes in appetite or weight. There was a significant
      difference (p = 0.03) between the classes based on alcohol use; those in the
      moderate depressive class were 1.71 times more likely to be identified as not
      reporting past alcohol use. Results indicated the high depressive class was
      estimated to have 1.62 more days of past year alcohol use than those in the
      moderate depressive class for adolescents who used alcohol (p < 0.001).
      Conclusions/Importance: Study findings can be used to address these significant
      public health issues impacting Hispanic adolescents. Recommendations are
      included.

PMID- 29053394
TI  - Vedroprevir in the management of hepatitis C virus infection.
AB  - INTRODUCTION: Hepatitis C Virus (HCV) is a chronic infection of the liver and the
      leading cause of liver failure and liver transplantation worldwide. While prior
      HCV therapies were prolonged and had variable success rates, the advent of direct
      acting antivirals (DAAs) has dramatically improved HCV therapy with minimal side
      effects, shorter treatment durations, and higher cure rates. Areas covered: In
      this paper, we review the literature discussing the use of Vedroprevir (GS-9451)
      in treatment of HCV in a variety of patient populations. Articles accessible on
      MEDLINE/PubMed were reviewed to provide context on chemistry, pharmacology, and
      efficacy of Vedroprevir in HCV treatment. Expert opinion: Vedroprevir is highly
      effective in reducing treatment duration in combination with other DAAs without
      compromising treatment success rates. GS-9451 is insufficient as HCV monotherapy
      due to low threshold for development of high level of resistance and must be
      combined with other DAAs to achieve sustained virologic response (SVR).

PMID- 29053395
TI  - Overexpression of HN1L promotes cell malignant proliferation in non-small cell
      lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is a progressive malignant disease, involving
      the activation of oncogenes and inactivation of tumor suppressors. In this study,
      we identified and characterized a novel oncogene hematopoietic- and neurologic
      expressed sequence 1-like (HN1L) in human NSCLC. Overexpression of HN1L was
      frequently detected in primary NSCLC compared with their non-tumor counterparts
      (P < 0.001), which was significantly associated with tumor size (P = 0.022). In
      addition, Kaplan-Meier analysis showed that upregulation of HN1L correlated with
      worse overall survival (P = 0.029) and disease-free survival (P = 0.011) for
      NSCLC patients. Both in vitro and in vivo studies demonstrated that inhibition of
      HN1L expression with shRNA dramatically inhibited cell growth, adherent and non
      adherent colony formation, and tumorigenicity in nude mice. The positive
      correlation of HN1L expression and Ki67 level in a large NSCLC samples further
      suggested the key role of HN1L in the regulation of cell growth. Further study
      showed that knockdown of HN1L resulted in dramatic cell cycle arrest by
      interfering with MAPK pathway via interacting with RASA4 protein. In conclusion,
      HN1L plays a crucial role in the progression of NSCLC by contributing to
      malignant proliferation, with possible use as a new intervention point for
      therapeutic strategies.

PMID- 29053397
TI  - Combined Intravitreal and Systemic Antibiotic Therapy in a Patient with
      Syphilitic Uveitis.
AB  - PURPOSE: To report the novel use of combined intravitreal and systemic antibiotic
      therapy in a patient with syphilitic panuveitis and discuss the management of
      ocular syphilis. METHODS: Case report Results: A 45-year old heterosexual male
      with human immunodeficiency virus (HIV) presented with 1 month of blurry vision
      in both eyes. Clinical examination revealed a bilateral panuveitis. The patient
      denied history of genital lesions or rash, but did complain of difficulty hearing
      bilaterally. Treponemal EIA was positive, the RPR titer greater than 1:512
      dilution, and CSF VDRL 1:4. A diagnosis of neurosyphilis and ocular syphilis was
      made based on the clinical and laboratory findings. The patient was admitted for
      systemic intravenous antibiotic therapy, but was noted to have a penicillin
      allergy. Intravitreal ceftazidime was promptly administered bilaterally to
      achieve treponemacidal levels of antibiotic therapy. After penicillin
      desensitization protocol, the patient received 14 days of intravenous penicillin
      with clinical resolution. CONCLUSIONS: There are increasing reports of ocular
      syphilis in the United States and delay in diagnosis and management can lead to
      severe visual impairment and blindness. We report the first case of adjunct
      intravitreal antibiotic therapy in a penicillin allergic patient. As ocular
      syphilis is a form of bacterial endophthalmitis, combination intravitreal and
      systemic antibiotics may be considered.

PMID- 29053396
TI  - Embryonic stem cell secreted factors decrease invasiveness of triple-negative
      breast cancer cells through regulome modulation.
AB  - Stem cell microenvironments decrease the invasiveness of cancer cells, and
      elucidating the mechanisms associated with disease regression could further the
      development of targeted therapies for aggressive cancer subtypes. To this end, we
      applied an emerging technology, TRanscriptional Activity CEll aRray (TRACER), to
      investigate the reprogramming of triple-negative breast cancer (TNBC) cells in
      conditions that promoted a less aggressive phenotype. The repressive environment
      was established through exposure to mouse embryonic stem cell conditioned media
      (mESC CM). Assessment of carcinogenic phenotypes indicated that mESC CM exposure
      decreased proliferation, invasion, migration, and stemness in TNBC cells. Protein
      expression analysis revealed that mESC CM exposure increased expression of the
      epithelial protein E-cadherin and decreased the mesenchymal protein MMP9. Gene
      expression analysis showed that mESC CM decreased epithelial to mesenchymal
      transition (EMT) markers fibronectin, vimentin, and Snail. Over a period of 6 d,
      TRACER quantified changes in activity of 11 transcription factors (TFs)
      associated with oncogenic progression. The EMT profile was decreased in
      association with the activity of 7 TFs (Smad3, NF-kappaBeta, MEF2, GATA, Hif1,
      Sp1, and RXR). Further examination of Smad3 and GATA expression and
      phosphorylation revealed that mESC CM exposure decreased noncanonical Smad3
      phosphorylation and Smad3-mediated gene expression, increased GATA3 expression
      and phosphorylation, and resulted in a synergistic decrease in migration of GATA3
      overexpressing MDA-MB-231 cells. Collectively, the application of TRACER to
      examine TF activity associated with the transition of cancer cells to a less
      aggressive phenotype, as directed by mESC CM, identified novel mechanistic events
      linking the embryonic microenvironment to both favorable changes and cellular
      plasticity in TNBC cell phenotypes.

PMID- 29053399
TI  - New pathogenic variant in the FGF10 gene in the agenesis of lacrimal and salivary
      gland syndrome: Ophthalmological and genetic study.
AB  - Aplasia/agenesis of lacrimal and salivary glands is a rare congenital defect that
      has been associated with disturbances in fibroblast growth factor 10 (FGF10). It
      can present with symptoms of congenital lacrimal obstruction, dry eye, and dry
      mouth. We report the ophthalmological and genetic study of a 19-year-old woman
      and her relatives suffering from this syndrome. A new probably pathogenic variant
      is described in the FGF10 gene.

PMID- 29053398
TI  - The involvement of lncRNAs in the development and progression of pancreatic
      cancer.
AB  - Pancreatic cancer is one of the most malignant tumors that are difficult to
      diagnose at its early stage and there is no effective therapy. Recent studies
      uncovered that many non-protein-coding RNAs including the class of long noncoding
      RNAs (lncRNAs) are differentially expressed in various types of tumors and they
      are potent regulators of tumor progression and metastasis. LncRNA can mediate
      tumor initiation, proliferation, migration and metastasis through modulating
      epigenetic modification, alternative splicing, transcription, and protein
      translation. In this review, we discuss the molecular mechanism of lncRNAs in the
      involvement of tumor growth, survival, epithelial-mesenchymal transition, tumor
      microenvironment, cancer stem cells and chemoresistance in pancreatic ductal
      adenocarcinoma (PDAC).

PMID- 29053400
TI  - Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical
      Assays and Clinical Implementation in Non-Small-Cell Lung Cancer.
AB  - Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are
      currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment
      with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing.
      Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and
      Drug Administration-cleared complementary PD-L1 tests are available for both. PD
      L1 IHC assays used to assess PD-L1 expression in patients treated with programmed
      death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28
      8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1
      SP263 (SP263). Differences in antibodies and IHC platforms have raised questions
      about comparability among these assays and their diagnostic use. This review
      provides practical information to help physicians and pathologists understand
      analytical features and comparability of various PD-L1 IHC assays and their
      diagnostic use. Methods We reviewed and summarized published or otherwise
      reported studies (January 2016 to January 2017) on clinical trial and laboratory
      developed PD-L1 IHC assays (LDAs). Studies assessing the effect of diagnostic
      methods on PD-L1 expression levels were analyzed to address practical issues
      related to tissue samples used for testing. Results High concordance and
      interobserver reproducibility were observed with the 28-8, 22C3, and SP263
      clinical trial assays for PD-L1 expression on tumor cell membranes, whereas lower
      PD-L1 expression was detected with SP142. Immune-cell PD-L1 expression was
      variable and interobserver concordance was poor. Inter- and intratumoral
      heterogeneity had variable effects on PD-L1 expression. Concordance among LDAs
      was variable. Conclusion High concordance among 28-8, 22C3, and SP263 when
      assessing PD-L1 expression on tumor cell membranes suggests possible
      interchangeability of their clinical use for NSCLC but not for assessment of PD
      L1 expression on immune cells. Development of LDAs requires stringent
      standardization before their recommendation for routine clinical use.

PMID- 29053401
TI  - Are we prepared for emerging flaviviruses in Europe? Challenges for vaccination.
AB  - Tick-borne encephalitis and West Nile fever are endemic flavivirus diseases in
      Europe. Climate change, virus evolution, and social factors may increase the risk
      of these flavivirus infections and may lead to the emergence of other
      flaviviruses in Europe that are endemic in (sub)tropical regions of the world.
      Control of the spread of flaviviruses is very difficult considering the cycling
      of flaviviruses between arthropod vectors and animal reservoir hosts. The
      increasing threat of flavivirus infections emphasizes the necessity of a
      sustainable vector surveillance system, an active animal health surveillance
      system and an adequate human surveillance system for early detection of
      flavivirus infections. Vaccination is the most important approach to prevent
      flavivirus infections. Effective inactivated whole virus vaccines against tick
      borne encephalitis (TBE) infection are available. Implementation of TBE
      vaccination based on favorable cost-effectiveness estimates per region and per
      target group can reduce the disease burden of TBE infection. At present, several
      West Nile virus (WNV) vaccine candidates are in various stages of clinical
      development. A major challenge for WNV vaccine candidates is to demonstrate
      efficacy, because of the sporadic nature of unpredictable WNV outbreaks.
      Universal WNV vaccination is unlikely to be cost-effective, vaccination of high
      risk groups will be most appropriate to protect against WNV infections.

PMID- 29053402
TI  - What Are We Missing? False-Negative Cancers at Multiparametric MR Imaging of the
      Prostate.
AB  - Purpose To characterize clinically important prostate cancers missed at
      multiparametric (MP) magnetic resonance (MR) imaging. Materials and Methods The
      local institutional review board approved this HIPAA-compliant retrospective
      single-center study, which included 100 consecutive patients who had undergone MP
      MR imaging and subsequent radical prostatectomy. A genitourinary pathologist
      blinded to MP MR findings outlined prostate cancers on whole-mount pathology
      slices. Two readers correlated mapped lesions with reports of prospectively read
      MP MR images. Readers were blinded to histopathology results during prospective
      reading. At histopathologic examination, 80 clinically unimportant lesions (<5
      mm; Gleason score, 3+3) were excluded. The same two readers, who were not blinded
      to histopathologic findings, retrospectively reviewed cancers missed at MP MR
      imaging and assigned a Prostate Imaging Reporting and Data System (PI-RADS)
      version 2 score to better understand false-negative lesion characteristics.
      Descriptive statistics were used to define patient characteristics, including
      age, prostate-specific antigen (PSA) level, PSA density, race, digital rectal
      examination results, and biopsy results before MR imaging. Student t test was
      used to determine any demographic differences between patients with false
      negative MP MR imaging findings and those with correct prospective identification
      of all lesions. Results Of the 162 lesions, 136 (84%) were correctly identified
      with MP MR imaging. Size of eight lesions was underestimated. Among the 26 (16%)
      lesions missed at MP MR imaging, Gleason score was 3+4 in 17 (65%), 4+3 in one
      (4%), 4+4 in seven (27%), and 4+5 in one (4%). Retrospective PI-RADS version 2
      scores were assigned (PI-RADS 1, n = 8; PI-RADS 2, n = 7; PI-RADS 3, n = 6; and
      PI-RADS 4, n = 5). On a per-patient basis, MP MR imaging depicted clinically
      important prostate cancer in 99 of 100 patients. At least one clinically
      important tumor was missed in 26 (26%) patients, and lesion size was
      underestimated in eight (8%). Conclusion Clinically important lesions can be
      missed or their size can be underestimated at MP MR imaging. Of missed lesions,
      58% were not seen or were characterized as benign findings at second-look
      analysis. Recognition of the limitations of MP MR imaging is important, and new
      approaches to reduce this false-negative rate are needed. (c) RSNA, 2017 Online
      supplemental material is available for this article.

PMID- 29053404
TI  - Positive body image is positively associated with hedonic (emotional) and
      eudaimonic (psychological and social) well-being in British adults.
AB  - Studies examining associations between positive body image and well-being have
      used a limited array of measures of each construct. To rectify this, we asked an
      online sample of 1148 U.K. adults to complete a range of measures of positive
      body image (body appreciation, body image flexibility, body pride, body
      acceptance from others) and a multi-dimensional measure of well-being (emotional,
      psychological, and social). Results showed that, once the effects of age and body
      mass index (BMI) had been accounted for, body appreciation significantly
      predicted all dimensions of well-being. Other positive body image measures
      emerged as significant predictors, but patterns of associations were mixed across
      sex and well-being dimension. Additional analyses showed that women had
      significantly lower scores than men on most body image measures, and that BMI was
      negatively associated with all body image measures. These results have
      implications for the promotion of well-being, which we discuss.

PMID- 29053405
TI  - Evolution of Endoscopic Anterior Component Separation to a Precostal Access with
      a New Cylindrical Balloon Trocar.
AB  - INTRODUCTION: Endoscopic anterior component separation (ECS) techniques
      facilitate tension-free midline closure of wide ventral hernia defects. We
      describe a novel approach with a precostal incision and a new cylindrical ballon
      trocar. MATERIALS AND METHODS: A single-center analysis of 19 patients undergoing
      ECS between January 1, 2014 and August 2, 2017 was performed with regard to
      improvement of technique. We currently start with a lateral precostal incision.
      This access in a low-fat and stable area allows for easy identification of the
      external oblique muscle with the ribs functioning as dorsal abutment for entering
      the correct plane between external and internal oblique muscles. Then a trocar is
      inserted with a cylindrical ballon, thus providing sufficient pneumatic widening
      of the dissection plane. A second 5-mm port is inserted under direct vision below
      the 12th rib. From there a unidirectional incision of the external oblique
      aponeurosis is performed from subcostal to the inguinal ligament. If necessary,
      the cephalad muscular parts of the external oblique can be transected over
      several centimeters in both directions starting from the precostal incision.
      RESULTS: We documented no procedure-related complications apart from two
      hematomas that required no interventions. Four procedures were carried out on one
      side and the remaining ones bilaterally. In one case, a conversion to
      conventional open component separation was required due to extensive scarring
      after open cholecystectomy. There were no notable abdominal bulgings or lateral
      hernias during a structured postoperative follow-up period of 1 year
      postoperatively. DISCUSSION: The technique described offers advantages in terms
      of determination of the correct entry point for ECS, regardless of abdominal wall
      conditions and the precostal access allows for unidirectional dissection toward
      the inguinal ligament with only two trocars in total. The cylindrical shape of
      the ballon trocar provides adequate widening of the working space and ensures
      good overview for safe dissection.

PMID- 29053403
TI  - Human cytomegalovirus vaccine development: Immune responses to look into vaccine
      strategy.
AB  - Human cytomegalovirus (HCMV) causes considerable morbidity and disability in high
      risk, immunocompromised populations including recipients of solid organ
      transplants, and fetuses whose immune systems are not yet mature. Vaccines aimed
      at ameliorating the severity of disease and preventing HCMV infection can be
      categorized into two main approaches of vaccine design, with one focusing on
      virus modification and the other on individual antigens. However, no candidates
      in either class have been successful in achieving durable and protective
      immunity. Recent studies on the natural immune response provide new insight into
      HCMV vaccine strategy. In particular, studies have demonstrated that the
      incorporation of a pentameric complex is necessary for a vaccine to generate the
      potent neutralizing antibodies often seen in seropositive individuals. This
      review summarizes recent findings in the development of HCMV vaccines and key
      considerations that should be taken into vaccine design based on improved
      understanding of natural HCMV immunity.

PMID- 29053406
TI  - Super-Resolution Nanoscopy Imaging Applied to DNA Double-Strand Breaks.
AB  - Genomic deoxyribonucleic acid (DNA) is continuously being damaged by endogenous
      processes such as metabolism or by exogenous events such as radiation. The
      specific phosphorylation of histone H2AX on serine residue 139, described as
      gamma-H2AX, is an excellent indicator or marker of DNA double-strand breaks
      (DSBs). The yield of gamma-H2AX (foci) is shown to have some correlation with the
      dose of radiation or other DSB-causing agents. However, there is some discrepancy
      in the DNA DSB foci yield among imaging and other methods such as gel
      electrophoresis. Super-resolution imaging techniques are now becoming widely used
      as essential tools in biology and medicine, after a slow uptake of their
      development almost two decades ago. Here we compare several super-resolution
      techniques used to image and determine the amount and spatial distribution of
      gamma-H2AX foci formation after X-ray irradiation: stimulated emission depletion
      (STED), ground-state depletion microscopy followed by individual molecule return
      (GSDIM), structured illumination microscopy (SIM), as well as an improved
      confocal, Airyscan and HyVolution 2. We show that by using these super-resolution
      imaging techniques with as low as 30-nm resolution, each focus may be further
      resolved, thus increasing the number of foci per radiation dose compared to
      standard microscopy. Furthermore, the DNA repair proteins 53BP1 (after low-LET
      irradiations) and Ku70/Ku80 (from laser microbeam irradiation) do not always
      yield a significantly increased number of foci when imaged by the super
      resolution techniques, suggesting that gamma-H2AX, 53PB1 and Ku70/80 repair
      proteins do not fully co-localize on the units of higher order chromatin
      structure.

PMID- 29053407
TI  - Lung-RADS: Pushing the Limits.
AB  - In response to the recommendation of the U.S. Preventive Services Task Force and
      the coverage decision by the Centers for Medicare and Medicaid Services for lung
      cancer screening (LCS) computed tomography (CT), the American College of
      Radiology introduced the Lung CT Screening Reporting and Data System (Lung-RADS)
      in 2014 to standardize the reporting and management of screening-detected lung
      nodules. As with many first-edition guidelines, questions arise when such
      reporting systems are used in daily practice. In this article, a collection of 15
      LCS-related scenarios are presented that address situations in which the Lung
      RADS guidelines are unclear or situations that are not currently addressed in the
      Lung-RADS guidelines. For these 15 scenarios, the authors of this article provide
      the reader with recommendations that are based on their collective experiences,
      with the hope that future versions of Lung-RADS will provide additional guidance,
      particularly as more data from widespread LCS are collected and analyzed.
      (c)RSNA, 2017.

PMID- 29053408
TI  - Geographical differentials in uptake of antenatal care services in Nigeria.
AB  - Uptake of antenatal care (ANC) is poor in Nigeria; however, there are
      geographical variations. We investigated the relationship between place of
      residence, region and ANC utilization in Nigeria. Using data of the most recent
      demographic and health survey, the geographic predictors of ANC were modeled.
      Women in the rural areas were 79% less likely to have the recommended four ANC
      visits. The odds of a woman in southern Nigeria having four ANC visit are 4.347
      times the odds of a woman in northern Nigeria having the recommended ANC visit.
      We recommend increased coverage of maternal health services.

PMID- 29053409
TI  - Amnestic Heterosexism and Bystander Responses to Anti-Gay Bullying.
AB  - Amnestic heterosexism (AH) reflects the belief that, in contemporary society,
      people who are lesbian, gay, or bisexual (LGB) no longer experience
      discrimination related to sexual orientation. We investigated potential
      associations between individuals' AH beliefs and their responses to anti-gay
      bullying. Heterosexual undergraduates (N = 238) completed a measure of AH before
      responding to a scenario in which a man accuses another man of being a "fag." As
      expected, those with greater AH beliefs perceived the situation as less
      severe/dangerous, felt less personally responsible to intervene, and were more
      blaming toward the target of bullying. In multivariate analyses, AH was
      indirectly associated with intent to confront the perpetrator via a path of
      reduced personal responsibility. Our results indicate that beliefs denying the
      existence of discrimination based on sexual orientation reduce feelings of
      personal responsibility to address anti-gay bullying. In turn, low personal
      responsibility inhibits confrontation of those who perpetrate bullying behaviors.

PMID- 29053410
TI  - The effect of moderate-intensity exercise on nightly variability in objectively
      measured sleep parameters among older women.
AB  - OBJECTIVE/BACKGROUND: Exercise training has been demonstrated to beneficially
      influence mean-level measures of sleep; however, few studies have examined the
      impact of an exercise intervention on night-to-night variability in sleep. This
      study investigated whether four months of moderate-intensity exercise impacted
      night-to-night variability in sleep among older women. METHODS: Participants (n =
      49) were randomized to one of two moderate-intensity walking programs with
      different doses of energy expenditure: low-dose (n = 23: 8 kcal/kg of body weight
      per week) or high-dose (n = 26: 14 kcal/kg of body weight per week). Sleep
      parameters were assessed objectively via actigraphy at baseline, mid- (2 months),
      and postintervention (4 months). Nightly variability in each of the sleep
      parameters was calculated using the seven-day standard deviation (SD) and a
      coefficient of variation (SD/mean x 100%). Cardiorespiratory fitness (VO2peak)
      was measured at baseline and postintervention using a graded treadmill test.
      RESULTS: Both measures of nightly variability demonstrated a borderline to
      significantly lower amount of night-to-night variability in wake time after sleep
      onset (WASO) and number of awakenings at postintervention in comparison to
      baseline (p <= 0.05). Higher VO2peak levels at baseline were associated with less
      time in bed and lower total sleep time variability throughout the exercise
      intervention (p < 0.05). CONCLUSION: Overall, participation in moderate-intensity
      exercise was observed to reduce the amount of nightly variability for WASO and
      number of awakenings over time in older women.

PMID- 29053414
TI  - PERK-Phosphorylated eIF2alpha Pathway Suppresses Tumor Metastasis Through
      Downregulating Expression of Programmed Death Ligand 1 and CXCL5 in Triple
      Negative Breast Cancer.
AB  - Endoplasmic reticulum (ER) stress has been reported to be associated with
      metastasis in many malignant tumors. PKR-like ER kinase-phosphorylated eukaryotic
      translation initiation factor 2alpha (PERK-p-eIF2alpha) pathway is one of the
      three main signal pathways in ER stress, however, its mechanism in regulating
      breast cancer (BC) relapse or metastasis was still not completely understood.
      Besides, drug resistance was an important factor influencing the effect of tumor
      treatment and whether PERK-p-eIF2alpha pathway was involved in the drug
      resistance to BC treatment also needs to be explored. The authors conducted
      survival analysis of ER stress-related genes in the The Cancer Genome Atlas
      (TCGA) database to find the candidate molecule and found that eIF2alpha was
      significantly correlated with relapse-free survival in BC patients, especially in
      the triple-negative BC (TNBC) patients. Furthermore, BC cell lines were used to
      study the downstream target of PERK-p-eIF2alpha. In this study, p-eIF2alpha could
      negatively regulate the expression of programmed death ligand 1 (PDL1) and C-X-C
      motif chemokine ligand 5 (CXCL5), which were important ligands of the immune
      cells such as T cells and myeloid-derived suppressor cells in the tumor
      microenvironment. Besides, p-eIF2alpha expression in highly metastatic human TNBC
      cells after treatment of carboplatin was significantly decreased. The data
      indicated the possible novel immune-related mechanism of PERK-p-eIF2alpha in
      regulating TNBC metastasis and drug resistance of carboplatin in highly
      metastatic TNBC.

PMID- 29053415
TI  - Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to
      Activate Murine Dendritic Cells.
AB  - AIM: Considering the central role of dendritic cells (DCs) on the development of
      an antitumor immune response, in this study we used a murine model to evaluate
      how DC transfection with drug-treated tumor cell RNA changes their phenotype, and
      whether transfection enhances the in vivo effectiveness of a DC-based antitumor
      vaccine. MATERIALS AND METHODS: MC-38 colorectal tumor cells were pretreated with
      the minimum effective concentration of 5-fluorouracil (5-FU), then their total
      RNA was extracted and transfected into DCs. These DCs were inoculated into
      C57Bl/6 mice bearing subcutaneous MC-38 tumor. RESULTS: DC transfection with drug
      treated tumor RNA increases the percentages of CD40+ (from 37.6% to 61.4%), CD86+
      (from 39.8% to 53.4%), and major histocompatibility complex class II+ (from 51.2%
      to 75.3%) cells, whereas significantly increases the in vivo generation of
      interferon-gamma producer lymphocytes. CONCLUSION: These results reinforce our
      view that treatment of tumor cells with 5-FU induces transcriptional changes that
      can be transferred to DCs by RNA transfection, enhancing their ability to
      stimulate an antitumor response.

PMID- 29053417
TI  - HIF-1alpha Promotes Breast Cancer Cell MCF-7 Proliferation and Invasion Through
      Regulating miR-210.
AB  - OBJECTIVE: Many malignant tumors grow in hypoxic condition, which is associated
      with tumor growth, invasion, and metastasis. MicroRNAs are of great significance
      in the development of multiple malignant tumors. This study cultured breast
      cancer cell MCF-7 under the condition of different concentrations of oxygen, to
      test cell proliferation and invasion, and detect miR-210 expression, aiming to
      analyze the influence of hypoxia on breast cancer cell behaviors as well as miR
      210 expressions. MATERIALS AND METHODS: Breast cancer cell MCF-7 was cultured
      under normoxia, hypoxia, or anaerobic conditions for 12, 24, or 48 hours. Cell
      proliferation was detected by MTT assay. Cell invasion and migration were tested
      by transwell assay. HIF-1alpha mRNA and miR-210 expressions were determined by
      real-time polymerase chain reaction. RESULTS: MCF-7 cell proliferation was
      gradually increased following time extension (p < 0.05). MCF-7 cell exhibited
      higher proliferation, invasion, and migration activities in hypoxic and anaerobic
      groups compared with those in normoxic group during the same time period. HIF
      1alpha mRNA and miR-210 were significantly upregulated in anaerobic group
      compared with those in other groups (p < 0.05). HIF-1alpha mRNA and miR-210 were
      obviously elevated at 12, 24, and 48 hours (p < 0.05). CONCLUSION: MCF-7 cell
      proliferation was increased, invasion and migration were enhanced, with
      upregulated expression of HIF-1alpha mRNA and miR-210 in the hypoxic and
      anaerobic group following time extension.

PMID- 29053416
TI  - Imaging of Integrin alphavbeta3 Expression in Lung Cancers and Brain Tumors Using
      Single-Photon Emission Computed Tomography with a Novel Radiotracer 99mTc-IDA-D
      [c(RGDfK)]2.
AB  - Integrin alphavbeta3 is a molecular marker for the estimation of tumor
      angiogenesis and is an imaging target for radiolabeled Arg-Gly-Asp (RGD)
      peptides. In this study, the authors investigated the clinical efficacy and
      safety of a novel radiolabeled RGD peptide, 99mTc-IDA-D-[c(RGDfK)]2, for the
      imaging of integrin alphavbeta3 expression, as a measure of tumor angiogenesis in
      lung cancers and brain tumors. Five patients with lung cancers and seven with
      brain tumors underwent 99mTc-IDA-D-[c(RGDfK)]2 single-photon emission computed
      tomography (SPECT) imaging. Tumors were also assessed using 18F
      fluorodeoxyglucose positron emission tomography/computed tomography. Uptake of
      the radiotracer was expressed as the tumor-to-normal uptake ratio (TNR). All the
      lung cancers and brain tumors were well visualized on 99mTc-IDA-D-[c(RGDfK)]2
      SPECT. TNR for 99mTc-IDA-D-[c(RGDfK)]2 was significantly higher than that for 18F
      FDG in brain tumors (6.4 +/- 4.1 vs. 0.9 +/- 0.4). Proliferation index of brain
      tumors showed a significant positive correlation with TNR for 99mTc-IDA-D
      [c(RGDfK)]2 and 18F-FDG. No laboratory and clinical adverse events were reported
      after 99mTc-IDA-D-[c(RGDfK)]2 injection. Their results suggest that 99mTc-IDA-D
      [c(RGDfK)]2 is an efficacious and safe radiotracer for imaging integrin
      alphavbeta3 expression with potential application to monitoring the clinical
      efficacy of antiangiogenic agents in malignant tumors. In addition, this is the
      first clinical application of radiolabeled RGD peptides for SPECT imaging of
      brain tumors.

PMID- 29053418
TI  - An Overview of Unfolded Protein Response Signaling and Its Role in Cancer.
AB  - Secretory and transmembrane proteins undergo post-translational modifications and
      folding in the subcellular organelle, that is, endoplasmic reticulum (ER) to
      become functionally active. Various factors such as high oxidative stress, low
      glucose, calcium imbalance, and viral infections interfere with the ER protein
      folding functions, leading to accumulation of unfolded and misfolded proteins
      that activate downstream signal transduction pathways, termed as unfolded protein
      response (UPR). This UPR signaling is adaptive and restored the normal function
      of cells by decreasing protein synthesis, increasing the folding capacity of ER
      and degradation of misfolded proteins. If the stress condition is overwhelmed,
      then UPR signaling shifts to apoptotic pathways. However, cancer cells utilized
      these UPR signaling for their survival and progression as an adaptive mechanism.
      In this review, the authors discuss about the overview of ER stress and
      subsequent UPR signaling and various aspects of cancer as survival,
      proliferation, and angiogenesis in relation to UPR. Understanding the UPR
      signaling in relation to cancer will be further helpful in designing therapeutics
      against cancer.

PMID- 29053419
TI  - Enhanced Sanitation Standard Operating Procedures Have Limited Impact on Listeria
      monocytogenes Prevalence in Retail Delis.
AB  - In a recent longitudinal surveillance study in 30 U.S. retail delicatessens, 9.7%
      of environmental surfaces were positive for Listeria monocytogenes, and we found
      substantial evidence of persistence. In this study, we aimed to reduce the
      prevalence and persistence of L. monocytogenes in the retail deli environment by
      developing and implementing practical and feasible intervention strategies (i.e.,
      sanitation standard operating procedures; SSOPs). These SSOPs were standardized
      across the 30 delis enrolled in this study. SSOP implementation was verified by
      systems inherent to each retailer. Each deli also was equipped with ATP
      monitoring systems to verify effective sanitation. We evaluated intervention
      strategy efficacy by testing 28 food and nonfood contact surfaces for L.
      monocytogenes for 6 months in all 30 retail delis. The efficacy of the
      intervention on the delis compared with preintervention prevalence level was not
      statistically significant; we found that L. monocytogenes could persist despite
      implementation of enhanced SSOPs. Systematic and accurate use of ATP monitoring
      systems varied widely among delis. The findings indicate that intervention
      strategies in the form of enhanced daily SSOPs were not sufficient to eliminate
      L. monocytogenes from highly prevalent and persistently contaminated delis and
      that more aggressive strategies (e.g., deep cleaning or capital investment in
      redesign or equipment) may be necessary to fully mitigate persistent
      contamination.

PMID- 29053420
TI  - Systematic Investigation of the Reduction of Inorganic Arsenic and Bioactive
      Nutrients in Rice with Various Cooking Techniques.
AB  - The objectives of this study were to investigate the effect of polishing,
      stirring and rinsing, soaking, or pressure-steam cooking on total organic and
      inorganic arsenic content and to measure daily inorganic arsenic exposure and
      nutrient values from consumption of rice prepared under the optimal process. With
      increasing numbers of rinses and times stirred per rinse, the total arsenic
      content significantly decreased by 27.6% in brown rice and 39.0% in white rice
      with 10% degree of polishing (10DOP%). The increase in ratio of water to rice
      from 1.5:1 to 6:1 reduced total arsenic by 4.4 to 7.5%, depending on soaking
      time. The total arsenic concentrations found in samples prepared using the
      optimal process for cooked brown rice and for white rice with 5DOP%, 7DOP%, and
      10DOP% were 56.1, 49.6, 52.0, and 42.0%, respectively, compared with those after
      bran residues were removed. The concentration of total dietary fiber in 10DOP%
      white and brown rice was 0.34 mg/100 g (54.7% reduction) and 2.52 mg/100 g (24.8%
      reduction) after the cooking process, respectively. Results from the current
      study suggest that the optimal cooking process could maximize the reduction of
      arsenic contents and, at the same time, minimize the loss of nutrients from rice.

PMID- 29053421
TI  - Development of a Novel Herbal Formulation To Inhibit Biofilm Formation in
      Toxigenic Vibrio cholerae.
AB  - Vibrio cholerae, a causative agent of the waterborne disease cholera, still
      threatens a large proportion of world's population. The role of biofilm formation
      in V. cholerae pathogenesis is well established, as it provides the bacterium
      enhanced tolerance to antimicrobial agents and increased transmission. In the
      present study, four medicinal plants used in traditional medicines with
      antidiarrheal properties were evaluated for its antibiofilm activity. Methanol
      extracts of these plants (Centella asiatica, Elephantopus scaber, Camellia
      sinensis, and Holarrhena antidysenterica) showed promising antibiofilm activity
      against V. cholerae with crystal violet and air-liquid interface coverslip
      assays. Results revealed that C. asiatica, E. scaber, C. sinensis, and H.
      antidysenterica extracts significantly inhibited biofilm formation by
      approximately 75, 76, 78, and 55% at concentrations of 3, 2, 1, and 0.6 mg/mL,
      respectively. A promising antibiofilm activity of ~89% inhibition at 1.5 mg/mL
      concentration was observed when a combination of E. scaber and C. sinensis was
      used. The herbal extracts were thermostable at a temperature range of 40 to 100
      degrees C. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      revealed that the viability of bacteria was not affected by treatment with these
      plant extracts. Gene expression studies revealed that extracts of H.
      antidysenterica leaf, H. antidysenterica bark, and the whole plant of E. scaber
      and C. asiatica down-regulate aphA or aphB, the major regulator genes modulating
      both virulence and biofilm formation. Hence, we propose that these herbal
      combinations could serve as a multifaceted approach to combat the pathogen and
      also, in turn, reduce antimicrobial resistance development.

PMID- 29053422
TI  - Evaluation of Third-Party Deep Cleaning as a Listeria monocytogenes Control
      Strategy in Retail Delis.
AB  - The objective of this study was to develop and assess the efficacy of an
      aggressive deep cleaning sanitation standard operating procedure (DC-SSOP) in
      nine retail delicatessens to reduce persistent Listeria monocytogenes
      environmental contamination. The DC-SSOP was developed from combined daily SSOPs
      recommended by the Food Marketing Institute and input from experts in Listeria
      control from food manufacturing and sanitation. The DC-SSOP was executed by a
      trained professional cleaning service during a single 12-h shutdown period. A
      modified protocol from the U.S. Food and Drug Administration Bacteriological
      Analytical Manual was used to detect L. monocytogenes in samples from 28 food and
      nonfood contact surfaces that were collected immediately before and after each
      cleaning and in samples collected monthly for 3 months. The DC-SSOP significantly
      reduced L. monocytogenes prevalence overall during the 3-month follow-up period
      and produced variable results for persistent L. monocytogenes isolates. Six delis
      with historically low to moderate L. monocytogenes prevalence had no significant
      changes in the number of samples positive for L. monocytogenes after deep
      cleaning. Deep cleaning in very high prevalence delis (20 to 30% prevalence)
      reduced L. monocytogenes by 25.6% (Padj < 0.0001, n = 294) overall during the
      follow-up period. Among delis with extremely high prevalence (>30%), positive
      samples from nonfood contact surfaces were reduced by 19.6% (Padj = 0.0002, n =
      294) during the follow-up period. The inability of deep cleaning to completely
      eliminate persistent L. monocytogenes was likely due to the diverse
      infrastructures in each deli, which may require more individualized intervention
      strategies.

PMID- 29053305
TI  - Search for Charged Higgs Bosons Produced via Vector Boson Fusion and Decaying
      into a Pair of W and Z Bosons Using pp Collisions at sqrt[s]=13  TeV.
AB  - A search for charged Higgs bosons produced via vector boson fusion and decaying
      into W and Z bosons using proton-proton collisions at sqrt[s]=13  TeV is
      presented. The data sample corresponds to an integrated luminosity of 15.2  fb^{
      1} collected with the CMS detector in 2015 and 2016. The event selection requires
      three leptons (electrons or muons), two jets with large pseudorapidity separation
      and high dijet mass, and missing transverse momentum. The observation agrees with
      the standard model prediction. Limits on the vector boson fusion production cross
      section times branching fraction for new charged physical states are reported as
      a function of mass from 200 to 2000 GeV and interpreted in the context of Higgs
      triplet models.

PMID- 29053423
TI  - Lasioderma serricorne (Coleoptera: Anobiidae): First Report on Black Sesame
      (Sesamum indicum).
AB  - Insect pests may make food products and by-products unfit for human consumption.
      This study reports the occurrence of Lasioderma serricorne (Coleoptera:
      Anobiidae) in packaged seeds of black Sesamum indicum. An intact plastic pot of
      S. indicum seeds was purchased by a consumer in a supermarket in Divinopolis,
      Minas Gerais state, Brazil, in April 2014 and was kept at his home for 3 months.
      Two hundred adults of this insect (196 dead and 4 alive) were counted in the pot
      with the seeds, besides three live larvae. This insect fed on S. indicum seeds,
      making them unfit for consumption. L. serricorne feed on and reproduce in S.
      indicum seeds stored in plastic packaging.

PMID- 29053426
TI  - Anti-hLCN6 Monoclonal Antibody.

PMID- 29053425
TI  - Association of Mannose-Binding Lectin rs1800450 and Tumor Necrotic Factor-alpha
      rs1800620 Polymorphism with Helicobacter pylori in Type II Diabetes Mellitus.
AB  - Type II diabetes mellitus (T2DM) is the prevalent type of diabetes, including 90%
      of the cases world-wide. Helicobacter pylori plays a pathogenic role in the
      development of T2DM. The host genetic factors have a significant impact on the
      clinical outcome and anatomical distribution of H. pylori infection and
      polymorphisms in several genes such as tumor necrotic factor (TNF)-alpha and
      mannose-binding lectin (MBL) and are considered to increase the risk for the
      development of T2DM. In this study, we investigate the prevalence rate of H.
      pylori infection and its relationship to MBL rs1800450 and TNF-alpha rs1800620
      polymorphism in T2DM. In this case-control study, 174 patients with type II
      diabetes and 185 healthy controls were studied. Also, demographics, physical, and
      biochemical parameters were performed in all patients. The DNA extracted from
      blood specimens was amplified by H. pylori cagA-specific primers. The MBL
      rs1800450 and TNF-alpha rs1800620 genotyping were detected by amplification
      refractory mutation system-polymerase chain reaction (ARMS-PCR). The results show
      that H. pylori cagA positivity was detected in 42.82% of the diabetic patients
      and in 22.16% of the control group, and H. pylori infection was closely
      correlated with MBL rs1800450 AA genotype and TNF-alpha rs1800620 GG genotype
      when compared with healthy controls. Furthermore, these two genotypes were
      strongly associated with H. pylori cagA(+) samples when compared with cagA(-)
      samples. In addition, the presence of H. pylori cagA(+) infection was
      significantly associated with the elevated serum levels of total cholesterol and
      low-density lipoprotein cholesterol. In general, it can be concluded that
      molecular analysis of MBL rs1800450 AA genotype and TNF-alpha rs1800620 AA
      genotype is important in the early detection and treatment of T2DM with H. pylori
      cagA(+) infection.

PMID- 29053428
TI  - DUST-BATHING BEHAVIORS OF AFRICAN HERBIVORES AND THE POTENTIAL RISK OF
      INHALATIONAL ANTHRAX.
AB  - :  Anthrax in herbivorous wildlife and livestock is generally assumed to be
      transmitted via ingestion or inhalation of Bacillus anthracis spores. Although
      recent studies have highlighted the importance of the ingestion route for anthrax
      transmission, little is known about the inhalational route in natural systems.
      Dust bathing could aerosolize soilborne pathogens such as B. anthracis, exposing
      dust-bathing individuals to inhalational infections. We investigated the
      potential role of dust bathing in the transmission of inhalational anthrax to
      herbivorous wildlife in Etosha National Park, Namibia, an area with endemic
      seasonal anthrax outbreaks. We 1) cultured soils from dust-bathing sites for the
      presence and concentration of B. anthracis spores, 2) monitored anthrax carcass
      sites, the locations with the highest B. anthracis concentrations, for evidence
      of dust bathing, including a site where a zebra died of anthrax on a large dust
      bath, and 3) characterized the ecology and seasonality of dust bathing in plains
      zebra ( Equus quagga), blue wildebeest ( Connochaetes taurinus), and African
      savanna elephant ( Loxodonta africana) using a combination of motion-sensing
      camera traps and direct observations. Only two out of 83 dust-bath soils were
      positive for B. anthracis, both with low spore concentrations (<=20 colony
      forming units per gram). We also detected no evidence of dust baths occurring at
      anthrax carcass sites, perhaps due to carcass-induced changes in soil composition
      that may deter dust bathing. Finally, despite observing some seasonal variation
      in dust bathing, preliminary evidence suggests that the seasonality of dust
      bathing and anthrax mortalities are not correlated. Thus, although dust bathing
      creates a dramatic cloud of aerosolized soil around an individual, our
      microbiologic, ecologic, and behavioral results in concert demonstrate that dust
      bathing is highly unlikely to transmit inhalational anthrax infections.

PMID- 29053430
TI  - GASTROINTESTINAL PARASITIC INFECTIONS IN DEAD OR DEBILITATED MOOSE ( ALCES ALCES)
      IN SWEDEN.
AB  - :  Our objectives were to determine prevalence and intensity of gastrointestinal
      parasites of dead or euthanized emaciated moose in central and southern Sweden (
      n=50) and to assess parasite intensity as a major contributing factor in the poor
      condition of these moose. All animals were infected and most had gastrointestinal
      nematodes. Seven parasite species were found in the abomasa and 10 species were
      found in the small intestine. Coinfections were commonly found in the abomasum (
      Ostertagia antipini and Mazamastrongylus dagestanica) and in the small intestine
      ( Nematodirella alcidis and Trichostrongylus capricola). Moose had many
      nematodes; the highest numbers were 224,400 and 11,760, in the abomasum and in
      the small intestine, respectively. Fourteen moose had more than 40,000
      gastrointestinal nematodes (excluding large intestine nematodes represented by
      Trichuris spp. and Oesophagostomum venulosum). Additionally, a moderate
      prevalence (36%) of protostrongylid larvae (dorsal spine larvae) and a low
      prevalence (2-4%) of protozoal infections were identified at microscopic
      examination of feces. Adult moose had significantly more parasites than did
      subadults. The results did not show parasite load as a single or a major cause of
      the moose mortality, but they provided an update on the species composition of
      helminth parasites in moose in Sweden and illustrated the extreme infection
      intensities that free-ranging moose can have.

PMID- 29053431
TI  - SURVEY OF GROSS AND HISTOPATHOLOGIC FINDINGS IN TWO WINTERING SUBPOPULATIONS OF
      SANDHILL CRANES ( ANTIGONE CANADENSIS).
AB  - :  Sandhill Cranes ( Antigone canadensis) of the midcontinent population (MCP)
      and Rocky Mountain population (RMP) are migratory game birds with stable
      populations that travel between Canada and the southern US and Mexico. In the
      winters of 2012-14, we performed gross and histologic examinations of 43 hunter
      harvested Sandhill Cranes in Texas (MCP) and New Mexico (RMP) to assess the
      impact of disease on populations. Lesions were significantly more common in the
      MCP relative to the RMP, likely reflecting differential environmental exposure to
      pathogens and parasites. Grossly, liver nodules and esophageal granulomas were
      present in 8-39% of birds. In feces from over half of birds, we found coccidian
      oocysts with mitochondrial gene sequences identical to those of Eimeria gruis and
      Eimeria reichenowi previously obtained from sympatric Whooping Cranes ( Grus
      americana). Over one-quarter of birds had liver and cardiac lesions suggestive of
      disseminated visceral coccidiosis. We documented proliferative colitis due to
      Cryptosporidium in a wild Sandhill Crane. Additionally, several endoparasites
      were found in histologic sections from several cranes, including a bird with
      respiratory trematodiasis and two birds with Tetrameres sp. in the proventriculus
      associated with ductal ectasia. In addition to describing lesions and parasites
      that impact Sandhill Crane health, these pathology data may also be relevant for
      the conservation of endangered Whooping Cranes using a surrogate species
      approach.

PMID- 29053427
TI  - CANINE DISTEMPER VIRUS IN A WILD FAR EASTERN LEOPARD ( PANTHERA PARDUS
      ORIENTALIS).
AB  - The critically endangered population of Far Eastern leopards ( Panthera pardus
      orientalis) may number as few as 60 individuals and is at risk from stochastic
      processes such as infectious disease. During May 2015, a case of canine distemper
      virus (CDV) was diagnosed in a wild leopard exhibiting severe neurologic disease
      in the Russian territory of Primorskii Krai. Amplified sequences of the CDV
      hemagglutinin gene and phosphoprotein gene aligned within the Arctic-like clade
      of CDV, which includes viruses from elsewhere in Russia, China, Europe, and North
      America. Histologic examination of cerebral tissue revealed perivascular lymphoid
      cuffing and demyelination of the white matter consistent with CDV infection.
      Neutralizing antibodies against CDV were detected in archived serum from two wild
      Far Eastern leopards sampled during 1993-94, confirming previous exposure in the
      population. This leopard population is likely too small to maintain circulation
      of CDV, suggesting that infections arise from spillover from more-abundant
      domestic or wild carnivore reservoirs. Increasing the population size and
      establishment of additional populations of leopards would be important steps
      toward securing the future of this subspecies and reducing the risk posed by
      future outbreaks of CDV or other infectious diseases.

PMID- 29053424
TI  - L-Carnitine and Potential Protective Effects Against Ischemia-Reperfusion Injury
      in Noncardiac Organs: From Experimental Data to Potential Clinical Applications.
AB  - The mechanism of ischemia-reperfusion (I/R) injury is complex and multifactorial.
      In this condition, systemic event results in morbidity and mortality in several
      pathologies, including myocardial infarction, ischemic stroke, acute kidney
      injury, trauma, and circulatory arrest. Hypoxia over ischemia phase leads to
      energy imbalance and changes of cellular homeostasis and functional or structural
      alterations. In addition, during the reperfusion period, some events, including
      calcium influx, release of intracellular enzymes, and cell membrane integrity
      breakdown, cause cell death. L-carnitine (LC) and its derivatives have been
      suggested to improve tolerance against I/R injury in various tissues. The
      favorable effects of LC are possibly mediated by its antioxidant and anti
      inflammatory effects or by other capability due to increase in the intracellular
      carnitine content. In this article, anti-ischemic properties of LC and its
      derivative in noncardiac organs are reviewed using relative animal and human
      research. Although most of the studies on noncardiac internal organs have shown
      protective effects of LC administration against I/R injury, more clinical trials
      are needed to clarify the clinical importance of LC as a treatment option for I/R
      induced injury.

PMID- 29053429
TI  - HOUSE FINCH ( HAEMORHOUS MEXICANUS)-ASSOCIATED MYCOPLASMA GALLISEPTICUM
      IDENTIFIED IN LESSER GOLDFINCH ( SPINUS PSALTRIA) AND WESTERN SCRUB JAY (
      APHELOCOMA CALIFORNICA) USING STRAIN-SPECIFIC QUANTITATIVE PCR.
AB  - :  In 1994 Mycoplasma gallisepticum was found to be the etiologic agent of House
      Finch ( Haemorhous mexicanus) conjunctivitis, a rapidly expanding epidemic caused
      by a genetically discrete, House Finch-associated strain of M. gallisepticum
      (HFMG). While most prominent in House Finches, HFMG has been reported in other
      members of the family Fringillidae, including American Goldfinches ( Spinus
      tristis), Purple Finches ( Haemorhous purpureus), Pine Grosbeaks ( Pinicola
      enucleator), and Evening Grosbeaks ( Coccothraustes vespertinus). Herein we
      report two new potential host species of HFMG strain, the Lesser Goldfinch (
      Spinus psaltria), belonging to the Fringillidae family, and the Western
      (California) Scrub Jay ( Aphelocoma californica), belonging to the Corvidae
      family. The latter is one of only two reports of HFMG being found outside the
      Fringillidae family, and of these is the only one reported outside of captivity.
      Furthermore, non-HFMG M. gallisepticum was identified in an American Crow (
      Corvus brachyrhynchos), indicating presence of additional strains in wild birds.
      Strain typing of M. gallisepticum isolates was done via HFMG-specific
      quantitative PCR analysis and validated using random amplified polymorphic DNA
      analysis. Our results suggested an expanded host range of HFMG strain, and
      further suggested that the host range of HFMG was not limited to members of the
      family Fringillidae.

PMID- 29053432
TI  - Integrating RNA Expression Identifies Candidate Gene for Orofacial Clefts.

PMID- 29053434
TI  - Alpha-Gal Inactivated Heart Valve Bioprostheses Exhibit an Anti-Calcification
      Propensity Similar to Knockout Tissues<sup/>.
AB  - BACKGROUND: Glutaraldehyde (GLA) has been used to crosslink bioprosthetic heart
      valve (BHVs) tissues to enhance their stability, besides ensuring a satisfactory
      degree of immunological tolerance. Unfortunately, GLA fixation does not guarantee
      a complete tissue biocompatibility of BHVs in currently used devices. The
      interaction between preformed human anti-alpha-Gal antibody and alpha-Gal
      antigens promotes the calcification of GLA-treated alpha-Gal-positive tissue.
      Recently, an alarming correlation between the presence of the alpha-Gal epitope
      and a premature BHVs degeneracy was reported. This article presents the results
      of a novel treatment called FACTA, for the inactivation of the alpha-Gal epitopes
      in porcine aortic valve tissue and commercial BHVs. METHODS: Evaluation of the
      alpha-Gal epitope inactivation was performed through a patented ELISA test,
      confirmed by western blot, immunofluorescence, and immunohistochemical analyses.
      Investigations were also conducted to assess the in vitro propensity to trigger
      thrombosis, calcification, and worsening of FACTA-treated tissue. To explain the
      mechanism of action through which the FACTA treatment acts, a specific
      experimental model, based on the mass spectroscopy approach, was performed.
      RESULTS: The study confirms that GLA is able to ensure the inactivation of
      approximately half alpha-Gal epitopes originally present in both porcine aortic
      valve tissue and marketed BHVs. By subjecting tissues to the FACTA procedure, it
      was possible to obtain an alpha-Gal inactivation degree of about 95% alongside to
      a reduced propensity from 72.6% to 85.4% to the in vitro calcification for
      porcine aortic valve tissue and 80.5% for commercial treated BHVs. FACTA was
      effective in decreasing oxidative tissue damage and protecting collagen from
      degradation. Finally, FACTA could further mitigate or even abrogate the need for
      early anticoagulation therapies after BHV implantation. CONCLUSION: A novel
      treatment, called FACTA, is effective to produce biological tissues that are less
      susceptible to enzymatic and oxidative stress and structural degradation,
      calcification, and thrombus formation. FACTA-treated tissues display a clear
      improvement of their biocompatibility that is characterized by an almost complete
      inactivation of the alpha-Gal epitope. FACTA prevents the xenogeneic tissue
      antigens from reacting with the host immune system, ensuring an effective shield
      effect that makes the tissue surface less reactive and more biocompatible.

PMID- 29053435
TI  - Temporal Occurrence and Niche Preferences of Phytophthora spp. Causing Brown Rot
      of Citrus in the Central Valley of California.
AB  - Brown rot of citrus fruit is caused by several species of Phytophthora and is
      currently of serious concern for the California citrus industry. Two species,
      Phytophthora syringae and P. hibernalis, are quarantine pathogens in China, a
      major export market for California citrus. To maintain trade and estimate the
      risk of exporting a quarantine pathogen, the distribution and frequency of
      Phytophthora spp. causing brown rot of orange in major growing areas of
      California was investigated. Symptomatic fruit were collected from navel (winter
      to late spring) and Valencia (late spring to summer) orange orchards from 2013 to
      2015. Species identification of isolates was based on morphological
      characteristics, random amplified polymorphic DNA banding patterns, and
      sequencing of the internal transcribed spacer and the partial cox2/spacer/cox1
      regions from axenic cultures, or directly on DNA from fruit tissue using a
      multiplex TaqMan quantitative polymerase chain reaction assay. In winter
      samplings, the incidence of P. syringae based on the number of fruit with
      Phytophthora spp. detection ranged from 73.6 to 96.1% for the two counties
      surveyed. The remaining isolates were identified as P. citrophthora. In late
      spring or summer, only P. citrophthora was recovered. P. hibernalis and P.
      nicotianae were not detected in any fruit with brown rot symptoms. These results
      indicate that P. syringae is currently an important brown rot pathogen of citrus
      fruit in California during the cooler seasons of the year. In winter 2016 and
      2017, P. syringae was recovered by pear baiting at a high incidence from leaf
      litter and from a small number of rhizosphere soil or root samples but not from
      living leaves on the tree. In contrast, P. citrophthora was rarely found in leaf
      litter but was commonly detected in the rhizosphere. Thus, leaf litter is a major
      inoculum source for P. syringae and this species occupies a distinct ecological
      niche.

PMID- 29053436
TI  - Is the Danish Version of MATE Feasible? A Pilot Study on Feasibility and
      Adequacy.
AB  - OBJECTIVE: Assessment is pivotal to the work of health care professionals and
      social workers, as it provides fundamental, systematic information that is
      essential when planning interventions. Many patients have addiction problems as
      well as psychiatric illness and they very often interact. An assessment tool
      addressing both areas would be beneficial for this large group of patients. This
      pilot study explores feasibility and adequacy of the Danish translation of the
      Measurements in Addiction for Triage and Evaluation (MATE) assessment in the
      following sectors: drug and alcohol treatment, psychiatry, and social service.
      METHODS: Thirty staff members from psychiatric hospital, social services, and
      treatment institutions for alcohol and substance abuse were recruited. Staff that
      had direct contact with clients were planned to perform at least two MATE
      interviews. RESULTS: Nineteen interviews were completed. Information gathered
      from MATE was reported to be adequate for making a triage decision, but
      psychiatric staff reported that MATE gathered too much irrelevant information,
      especially concerning daily life functioning. Overall feasibility was
      satisfactory, but staff and patients were at some points critical of wording,
      casting doubt on the understanding of some questions. CONCLUSIONS: This pilot
      study found that MATE gathers relevant and sufficient information in an
      appropriate amount of time.

PMID- 29053437
TI  - Reaching Egyptian Gays Using Social Media: A Comprehensive Health Study and a
      Framework for Future Research.
AB  - The Internet has revolutionized research on sexual minorities by providing direct
      and safe access to hidden, stigmatized, and high-risk populations. This study
      investigated the possibility of using Facebook to reach Egyptian gays. The
      questionnaire was manually distributed to an extensive list of Facebook pages and
      groups related to the topic that has been collected using a snowball-like
      technique. The recruitment lasted from August 2015 to May 2016. Among the 461
      eligible participants, the mean age was 26.6 (SD = 7.6), and the majority (74%)
      were highly educated. Only 17% use condoms consistently, and 34% have ever tested
      for HIV. Guilt feelings and trying to change sexual orientation were very high
      and were associated with higher religiosity and low condom use and HIV testing (p
      < .05). Also, 10% have ever tried to end their life. Most of the participants did
      not disclose their sexual orientation to anybody other than their partners, and
      60% will not disclose it to health care providers even if needed. The low health
      awareness among Egyptian gays requires Internet-based health campaigns.

PMID- 29053439
TI  - Factors influencing Indonesian women's use of maternal health care services.
AB  - Employing the 2012 Indonesia Demographic and Health Survey data, we aimed to
      examine factors influencing married women to use maternity services. Data of
      married women who had given birth in the last five years before the survey were
      included in the analysis (n = 14,672). Factors of education, employment, women's
      age at first marriage, age at first birth, spousal education difference,
      contraceptive use, place of residence, and woman's attitude toward wife beating
      were associated with the use of antenatal care, institutional delivery, and
      postnatal care services. The likelihood of women using those recommended maternal
      health care services increased along with the increased educational attainment
      among women and their spouses, and the older age at first birth. Higher schooling
      years may contribute to improving adequate maternal health care. Community
      awareness on maternal health issues should be promoted and include the prevention
      of early marriage, teenage pregnancies, and domestic violence.

PMID- 29053438
TI  - Tailored Approach to Surgical Exposure Reduces Surgical Site Complications after
      Bilateral Lung Transplantation.
AB  - BACKGROUND: We evaluated the effects of tailoring the operative approach on major
      surgical site complications and outcomes in lung transplant recipients. PATIENTS
      AND METHODS: Beginning in July 2013, bilateral lung transplants at a single
      institution were performed either through sternotomy or clamshell depending on
      proximity of hilar structures by computed tomography (CT), anticipated
      complexity, past surgical history, and surgeon experience. Patient demographics
      and outcomes were collected in the institution's Transplant Information Services
      (TIS). A major surgical site complication was defined as a sterile or infected
      incision requiring operative intervention. RESULTS: One hundred six bilateral
      lung transplants (68 via clamshell and 38 via median sternotomy) were performed
      between July 2013 and June 2016. Median sternotomy patients were older (mean age
      55 vs. 50 y, p = 0.04), and less likely to have cystic fibrosis (5 [13%] vs. 19
      [28%], p = 0.21) or diabetes (5 [13%] vs. 26 [38%], p = 0.01). There was no
      statistically significant difference in mean lung allocation score (LAS) (45 vs.
      48, p = 0.39) and body mass index (BMI; kg/m2; 25.3 vs. 24.4, p = 0.29) between
      the sternotomy and clamshell group. Fifteen (14.2%) patients experienced a total
      of 25 surgical site complications (19 major and 6 minor). No sternotomy patient
      had a major surgical site complication and 11 (16.2%) clamshell patients had a
      major surgical site complication (p = 0.01). Of these 11 patients, 5 (45%)
      required multiple operative revisions related to the surgical site. Freedom from
      major surgical site complications at three years was 100% for sternotomy patients
      and 80% for clamshell patients (p = 0.017). CONCLUSIONS: Tailoring the operative
      approach can reduce surgical site complications in lung transplant patients by
      avoiding a clamshell whenever feasible.

PMID- 29053441
TI  - Response to Milholland et al. (Rejuvenation Res. 2017;20:437-440).

PMID- 29053440
TI  - Association of the HLA-B alleles with carbamazepine-induced Stevens-Johnson
      syndrome/toxic epidermal necrolysis in the Javanese and Sundanese population of
      Indonesia: the important role of the HLA-B75 serotype.
AB  - Carbamazepine (CBZ) is a common cause of life-threatening cutaneous adverse drug
      reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
      (TEN). Previous studies have reported a strong association between the HLA
      genotype and CBZ-induced SJS/TEN. We investigated the association between the HLA
      genotype and CBZ-induced SJS/TEN in Javanese and Sundanese patients in Indonesia.
      Nine unrelated patients with CBZ-induced SJS/TEN and 236 healthy Javanese and
      Sundanese controls were genotyped for HLA-B and their allele frequencies were
      compared. The HLA-B*15:02 allele was found in 66.7% of the patients with CBZ
      induced SJS/TEN, but only in 29.4% of tolerant control (p = 0.029; odds ratio
      [OR]: 6.5; 95% CI: 1.2-33.57) and 22.9% of healthy controls (p = 0.0021; OR:
      6.78; 95% CI: 1.96-23.38). These findings support the involvement of HLA-B*15:02
      in CBZ-induced SJS/TEN reported in other Asian populations. Interestingly, we
      also observed the presence of the HLA-B*15:21 allele. HLA-B*15:02 and HLA-B*15:21
      are members of the HLA-B75 serotype, for which a greater frequency was observed
      in CBZ-induced SJS/TEN (vs tolerant control [p = 0.0078; OR: 12; 95% CI: 1.90
      75.72] and vs normal control [p = 0.0018; OR: 8.56; 95% CI: 1.83-40]). Our
      findings suggest that screening for the HLA-B75 serotype can predict the risk of
      CBZ-induced SJS/TEN more accurately than screening for a specific allele.

PMID- 29053443
TI  - Enhancement of Intercellular Electrical Synchronization by Conductive Materials
      in Cardiac Tissue Engineering.
AB  - OBJECTIVE: cardiac tissue regeneration for the treatment of cardiovascular
      diseases has been of great research interest. Under the hypothesis that
      electrical synchronization of cardiac cells can be aided by conductive materials,
      electrically conductive scaffolds have been frequently used to improve cardiac
      tissue regeneration. However, theoretical analysis is presently absent in
      examining the underlying mechanism and rationally guiding the design of these
      conductive scaffolds. METHODS: here, equivalent-circuit models are proposed, in
      which two adjacent groups of cardiomyocytes are grown either on a bulk conductive
      substrate or around conductive nanostructures. When one group of cells leads with
      action potentials, the membrane depolarization of the following group is
      investigated. RESULTS: this study reveals that membrane depolarization of the
      following group is most sensitive to seal resistance to the substrate while
      surface roughness and conductivity of the material have less influence. In
      addition, it is found that a multiple-cell group is easier to be depolarized by
      its adjacent beating cardiomyocytes. For nanostructure-bridged cardiac cells,
      substantial depolarization occurs only with a seal resistance larger than 1013
      Omega/sqr, which is contradictory to many reported estimations. CONCLUSION: this
      work theoretically confirms the positive role of conductive scaffolds and
      nanostructures in aiding electrical synchronization of cardiac cells and reveals
      that its performance mainly relies on the cell-device interface. SIGNIFICANCE:
      this work provides a theoretical basis for the rational design of electroactive
      scaffolds for enhanced cardiac tissue engineering.

PMID- 29053442
TI  - Posterior parietal cortex estimates the relationship between object and body
      location during locomotion.
AB  - We test the hypothesis that the posterior parietal cortex (PPC) contributes to
      the control of visually guided locomotor gait modifications by constructing an
      estimation of object location relative to body state, and in particular the
      changing gap between them. To test this hypothesis, we recorded neuronal activity
      from areas 5b and 7 of the PPC of cats walking on a treadmill and stepping over a
      moving obstacle whose speed of advance was varied (slowed or accelerated with
      respect to the speed of the cat). We found distinct populations of neurons in the
      PPC, primarily in area 5b, that signaled distance- or time-to-contact with the
      obstacle, regardless of which limb was the first to step over the obstacle. We
      propose that these cells are involved in a sensorimotor transformation whereby
      information on the location of an obstacle with respect to the body is used to
      initiate the gait modification.

PMID- 29053444
TI  - An EM Simulation-Based Design Flow for Custom-Built MR Coils Incorporating Signal
      and Noise.
AB  - Developing custom-built MR coils is a cumbersome task, in which an a priori
      prediction of the coils' SNR performance, their sensitivity pattern, and their
      depth of penetration helps to greatly speed up the design process by reducing the
      required hardware manufacturing iterations. The simulation-based design flow
      presented in this paper takes the entire MR imaging process into account. That
      is, it includes all geometric and material properties of the coil and the
      phantom, the thermal noise as well as the target MR sequences. The proposed
      simulation-driven design flow is validated using a manufactured prototype coil,
      whose performance was optimized regarding its SNR performance, based on the
      presented design flow, by comparing the coil's measured performance against the
      simulated results. In these experiments, the mean and the standard deviation of
      the relative error between the simulated and measured coil sensitivity pattern
      were found to be and . Moreover, the peak deviation between the simulated and
      measured voxel SNR was found to be less than 4%, indicating that simulations are
      in good accordance with the measured results, validating the proposed software
      based design approach.

PMID- 29053445
TI  - Partition Level Constrained Clustering.
AB  - Constrained clustering uses pre-given knowledge to improve the clustering
      performance. Here we use a new constraint called partition level side information
      and propose the Partition Level Constrained Clustering (PLCC) framework, where
      only a small proportion of the data is given labels to guide the procedure of
      clustering. Our goal is to find a partition which captures the intrinsic
      structure from the data itself, and also agrees with the partition level side
      information. Then we derive the algorithm of partition level side information
      based on K-means and give its corresponding solution. Further, we extend it to
      handle multiple side information and design the algorithm of partition level side
      information for spectral clustering. Extensive experiments demonstrate the
      effectiveness and efficiency of our method compared to pairwise constrained
      clustering and ensemble clustering methods, even in the inconsistent cluster
      number setting, which verifies the superiority of partition level side
      information to pairwise constraints. Besides, our method has high robustness to
      noisy side information, and we also validate the performance of our method with
      multiple side information. Finally, the image cosegmentation application based on
      saliency-guided side information demonstrates the effectiveness of PLCC as a
      flexible framework in different domains, even with the unsupervised side
      information.

PMID- 29053446
TI  - Simulation of Constrained Musculoskeletal Systems in Task Space.
AB  - OBJECTIVE: This paper proposes an operational task space formalization of
      constrained musculoskeletal systems, motivated by its promising results in the
      field of robotics. METHODS: The change of representation requires different
      algorithms for solving the inverse and forward dynamics simulation in the task
      space domain. We propose an extension to the direct marker control and an
      adaptation of the computed muscle control algorithms for solving the inverse
      kinematics and muscle redundancy problems, respectively. RESULTS: Experimental
      evaluation demonstrates that this framework is not only successful in dealing
      with the inverse dynamics problem, but also provides an intuitive way of studying
      and designing simulations, facilitating assessment prior to any experimental data
      collection. SIGNIFICANCE: The incorporation of constraints in the derivation
      unveils an important extension of this framework toward addressing systems that
      use absolute coordinates and topologies that contain closed kinematic chains.
      Task space projection reveals a more intuitive encoding of the motion planning
      problem, allows for better correspondence between observed and estimated
      variables, provides the means to effectively study the role of kinematic
      redundancy, and most importantly, offers an abstract point of view and control,
      which can be advantageous toward further integration with high level models of
      the precommand level. CONCLUSION: Task-based approaches could be adopted in the
      design of simulation related to the study of constrained musculoskeletal systems.

PMID- 29053447
TI  - Multimodal MR Synthesis via Modality-Invariant Latent Representation.
AB  - We propose a multi-input multi-output fully convolutional neural network model
      for MRI synthesis. The model is robust to missing data, as it benefits from, but
      does not require, additional input modalities. The model is trained end-to-end,
      and learns to embed all input modalities into a shared modality-invariant latent
      space. These latent representations are then combined into a single fused
      representation, which is transformed into the target output modality with a
      learnt decoder. We avoid the need for curriculum learning by exploiting the fact
      that the various input modalities are highly correlated. We also show that by
      incorporating information from segmentation masks the model can both decrease its
      error and generate data with synthetic lesions. We evaluate our model on the
      ISLES and BRATS data sets and demonstrate statistically significant improvements
      over state-of-the-art methods for single input tasks. This improvement increases
      further when multiple input modalities are used, demonstrating the benefits of
      learning a common latent space, again resulting in a statistically significant
      improvement over the current best method. Finally, we demonstrate our approach on
      non skull-stripped brain images, producing a statistically significant
      improvement over the previous best method. Code is made publicly available at
      https://github.com/agis85/multimodal_brain_synthesis.

PMID- 29053448
TI  - The Effects of Coding Schemes on Vibrotactile Biofeedback for Dynamic Balance
      Training in Parkinson's Disease and Healthy Elderly Individuals.
AB  - Coding scheme for earlier versions of vibrotactile biofeedback systems for
      balance-related applications was primarily binary in nature, either on or off at
      a given threshold (range of postural tilt), making it unable to convey
      information about error magnitude. The purpose of this paper was to explore the
      effects of two coding schemes (binary versus continuous) for vibrotactile
      biofeedback during dynamic weight-shifting exercises that are common physical
      therapists' recommended balance exercises used in clinical settings. Nine
      individuals with idiopathic Parkinson's disease and nine healthy elderly
      individuals participated in this paper. All participants performed dynamic weight
      shifting exercises assisted with either the binary or continuous vibrotactile
      biofeedback delivered using with vibrating actuators (tactors) in either the
      anterior-posterior or medial-lateral direction. Participants' limits of stability
      at pre and post exercises were compared to evaluate the effects of the exercises
      on their range of motion. The continuous coding scheme produced significantly
      better performance than the binary scheme when both groups were performing
      dynamic weight-shifting balance exercises with assistive vibrotactile
      biofeedback. The results have implications in terms of maximizing the effects of
      error-driven motor learning and increasing performance on balance rehabilitation
      training combined with vibrotactile biofeedback.

PMID- 29053449
TI  - Thermo-Acoustic Ultrasound for Detection of RF-Induced Device Lead Heating in
      MRI.
AB  - Patients who have implanted medical devices with long conductive leads are often
      restricted from receiving MRI scans due to the danger of RF-induced heating near
      the lead tips. Phantom studies have shown that this heating varies significantly
      on a case-by-case basis, indicating that many patients with implanted devices can
      receive clinically useful MRI scans without harm. However, the difficulty of
      predicting RF-induced lead tip heating prior to scanning prevents numerous
      implant recipients from being scanned. Here, we demonstrate that thermo-acoustic
      ultrasound (TAUS) has the potential to be utilized for a pre-scan procedure
      assessing the risk of RF-induced lead tip heating in MRI. A system was developed
      to detect TAUS signals by four different TAUS acquisition methods. We then
      integrated this system with an MRI scanner and detected a peak in RF power
      absorption near the tip of a model lead when transmitting from the scanner's body
      coil. We also developed and experimentally validated simulations to characterize
      the thermo-acoustic signal generated near lead tips. These results indicate that
      TAUS is a promising method for assessing RF implant safety, and with further
      development, a TAUS pre-scan could allow many more patients to have access to MRI
      scans of significant clinical value.

PMID- 29053450
TI  - Two-Dimensional Isoelectric Focusing OFFGEL, Micro-Fluidic Lab-on-Chip
      Electrophoresis and FTIR for Assessment of Long-Term Stability of rhG-CSF
      Formulation.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been
      increasingly recognized from among one of the most abundant families of
      biosimilars. Upon long-term storage, the rhG-CSF is subject to subtle chemical
      modifications that rapidly occur and, in particular, produce deaminated variants
      with divergent charge. Indeed, changes in charge from glutamine deamination may
      alter the way rhG-SCF will refold and the structure of resulting molecule. To
      assess this charge heterogeneity, 2-D gel electrophoresis has limited
      application. Recent micro-fluidic- based technical advances offer a great
      alternative method to better control liquid volumes on a minute scale. Here, we
      used IEF OFFGEL-lab-on-chip electrophoresis for 2-D separation of the rhG-CSF
      peptides according to their isoelectric point (pI) and molecular weight (kDa). We
      used an rhG-CSF commercial therapeutic formulation, kept refrigerated 24 months
      after expiry. The samples were analyzed for particulate matter and charge
      variants. Subsequently, the secondary structure was assessed by FTIR spectroscopy
      and residual biological activity was recorded. Interestingly, we showed an
      additional band in the acidic gel area above and below the most intense protein
      band (fractions 10, 11, and 12 at 22.84s). This observation reveals the presence
      of the rhG-CSF variant charges without any additional high molecular weight
      impurity or biological activity decrease. We conclude that after two years of
      storage, the rhG-CSF solution maintained its native secondary structure with
      little -sheet deviation, as reflected in the 1622 cm-1 and 1695 cm-1. These data
      demonstrated that a combined strategy is a more suitable and accurate analytical
      assessment of the rhG-CSF and recombinant protein-based biosimilars.

PMID- 29053452
TI  - StreamExplorer: A Multi-Stage System for Visually Exploring Events in Social
      Streams.
AB  - Analyzing social streams is important for many applications, such as crisis
      management. However, the considerable diversity, increasing volume, and high
      dynamics of social streams of large events continue to be significant challenges
      that must be overcome to ensure effective exploration. We propose a novel
      framework by which to handle complex social streams on a budget PC. This
      framework features two components: 1) an online method to detect important time
      periods (i.e., subevents), and 2) a tailored GPU-assisted Self-Organizing Map
      (SOM) method, which clusters the tweets of subevents stably and efficiently.
      Based on the framework, we present StreamExplorer to facilitate the visual
      analysis, tracking, and comparison of a social stream at three levels. At a
      macroscopic level, StreamExplorer uses a new glyph-based timeline visualization,
      which presents a quick multi-faceted overview of the ebb and flow of a social
      stream. At a mesoscopic level, a map visualization is employed to visually
      summarize the social stream from either a topical or geographical aspect. At a
      microscopic level, users can employ interactive lenses to visually examine and
      explore the social stream from different perspectives. Two case studies and a
      task-based evaluation are used to demonstrate the effectiveness and usefulness of
      StreamExplorer.Analyzing social streams is important for many applications, such
      as crisis management. However, the considerable diversity, increasing volume, and
      high dynamics of social streams of large events continue to be significant
      challenges that must be overcome to ensure effective exploration. We propose a
      novel framework by which to handle complex social streams on a budget PC. This
      framework features two components: 1) an online method to detect important time
      periods (i.e., subevents), and 2) a tailored GPU-assisted Self-Organizing Map
      (SOM) method, which clusters the tweets of subevents stably and efficiently.
      Based on the framework, we present StreamExplorer to facilitate the visual
      analysis, tracking, and comparison of a social stream at three levels. At a
      macroscopic level, StreamExplorer uses a new glyph-based timeline visualization,
      which presents a quick multi-faceted overview of the ebb and flow of a social
      stream. At a mesoscopic level, a map visualization is employed to visually
      summarize the social stream from either a topical or geographical aspect. At a
      microscopic level, users can employ interactive lenses to visually examine and
      explore the social stream from different perspectives. Two case studies and a
      task-based evaluation are used to demonstrate the effectiveness and usefulness of
      StreamExplorer.

PMID- 29053451
TI  - Spatially Resolved MR-Compatible Doppler Ultrasound: Proof of Concept for
      Triggering of Diagnostic Quality Cardiovascular MRI for Function and Flow
      Quantification at 3T.
AB  - OBJECTIVE: We demonstrate the use of a magnetic-resonance (MR)-compatible
      ultrasound (US) imaging probe using spatially resolved Doppler for diagnostic
      quality cardiovascular MR imaging (MRI) as an initial step toward hybrid US/MR
      fetal imaging. METHODS: A newly developed technology for a dedicated MR
      compatible phased array ultrasound-imaging probe acquired pulsed color Doppler
      carotid images, which were converted in near-real time to a trigger signal for
      cardiac cine and flow quantification MRI. Ultrasound and MR data acquired
      simultaneously were interference free. Conventional electrocardiogram (ECG) and
      the proposed spatially resolved Doppler triggering were compared in 10 healthy
      volunteers. A synthetic "false-triggered" image was retrospectively processed
      using metric optimized gating (MOG). Images were scored by expert readers, and
      sharpness, cardiac function and aortic flow were quantified. Four-dimensional (4
      D) flow (two volunteers) showed feasibility of Doppler triggering over a long
      acquisition time. RESULTS: Imaging modalities were compatible. US probe
      positioning was stable and comfortable. Image quality scores and quantified
      sharpness were statistically equal for Doppler- and ECG-triggering (p ). ECG-,
      Doppler-triggered, and MOG ejection fractions were equivalent (p ), with false
      triggered values significantly lower (p < 0.0005). Aortic flow showed no
      difference between ECG- and Doppler-triggered and MOG (p > 0.05). 4-D flow
      quantification gave consistent results between ECG and Doppler triggering.
      CONCLUSION: We report interference-free pulsed color Doppler ultrasound during MR
      data acquisition. Cardiovascular MRI of diagnostic quality was successfully
      obtained with pulsed color Doppler triggering. SIGNIFICANCE: The hardware
      platform could further enable advanced free-breathing cardiac imaging. Doppler
      ultrasound triggering is applicable where ECG is compromised due to pathology or
      interference at higher magnetic fields, and where direct ECG is impossible, i.e.,
      fetal imaging.

PMID- 29053453
TI  - Distributed Continuous-Time Algorithms for Resource Allocation Problems Over
      Weight-Balanced Digraphs.
AB  - In this paper, a distributed resource allocation problem with nonsmooth local
      cost functions is considered, where the interaction among agents is depicted by
      strongly connected and weight-balanced digraphs. Here the decision variable of
      each agent is within a local feasibility constraint described as a convex set,
      and all the decision variables have to satisfy a network resource constraint,
      which is the sum of available resources. To solve the problem, a distributed
      continuous-time algorithm is developed by virtue of differentiated projection
      operations and differential inclusions, and its convergence to the optimal
      solution is proved via the set-valued LaSalle invariance principle. Furthermore,
      the exponential convergence of the proposed algorithm can be achieved when the
      local cost functions are differentiable with Lipschitz gradients and there are no
      local feasibility constraints. Finally, numerical examples are given to verify
      the effectiveness of the proposed algorithms.

PMID- 29053454
TI  - A Data Set for Camera-Independent Color Constancy.
AB  - In this paper, we provide a novel data set designed for Camera-independent color
      constancy research. Camera independence corresponds to the robustness of an
      algorithm's performance when it runs on images of the same scene taken by
      different cameras. Accordingly, the images in our database correspond to several
      laboratory and field scenes each of which is captured by three different cameras
      with minimal registration errors. The laboratory scenes are also captured under
      five different illuminations. The spectral responses of cameras and the spectral
      power distributions of the laboratory light sources are also provided, as they
      may prove beneficial for training future algorithms to achieve color constancy.
      For a fair evaluation of future methods, we provide guidelines for supervised
      methods with indicated training, validation, and testing partitions. Accordingly,
      we evaluate two recently proposed convolutional neural network-based color
      constancy algorithms as baselines for future research. As a side contribution,
      this data set also includes images taken by a mobile camera with color shading
      corrected and uncorrected results. This allows research on the effect of color
      shading as well.

PMID- 29053455
TI  - Co-Saliency Detection for RGBD Images Based on Multi-Constraint Feature Matching
      and Cross Label Propagation.
AB  - Co-saliency detection aims at extracting the common salient regions from an image
      group containing two or more relevant images. It is a newly emerging topic in
      computer vision community. Different from the most existing co-saliency methods
      focusing on RGB images, this paper proposes a novel co-saliency detection model
      for RGBD images, which utilizes the depth information to enhance identification
      of co-saliency. First, the intra saliency map for each image is generated by the
      single image saliency model, while the inter saliency map is calculated based on
      the multi-constraint feature matching, which represents the constraint
      relationship among multiple images. Then, the optimization scheme, namely cross
      label propagation, is used to refine the intra and inter saliency maps in a cross
      way. Finally, all the original and optimized saliency maps are integrated to
      generate the final co-saliency result. The proposed method introduces the depth
      information and multi-constraint feature matching to improve the performance of
      co-saliency detection. Moreover, the proposed method can effectively exploit any
      existing single image saliency model to work well in co-saliency scenarios.
      Experiments on two RGBD co-saliency datasets demonstrate the effectiveness of our
      proposed model.

PMID- 29053456
TI  - Localized Electroporation With Dielectrophoretic Field Flow Fractionation: Toward
      Removal of Circulating Tumour Cells From Human Blood.
AB  - This paper presents the design and experimental performance of a microelectrode
      based device to selectively lyse cells in a flow in a microfluidic channel.
      Localized cell lysis is achieved by utilizing "irreversible electroporation," in
      which cells are exposed to high magnitude electric pulses. Localized cell lysis
      in a flow has research applications and may allow for the removal of harmful
      cells, such as circulating tumor cells from blood. Due to the dependence of this
      technique on the magnitude of the applied electric field, lethal electric field
      regions can be localized in the channel by the calibration of the applied
      voltage. Dielectrophoresis field flow fractionation is used to levitate target
      cancer cells in the lethal region of the device microchannel. Experiments are
      performed to demonstrate the localized lysis of MCF7 cancer cells in a mixture of
      blood cells. Due to their larger size, these circulating tumor cell analogues
      levitate to a greater height in the channel than erythrocytes. MCF7 lysis is
      observed to increase from 4.6% in control experiments to 57.3% in active
      experiments. Leukocyte viability was unaffected in active experiments. These
      results demonstrate the feasibility of localizing cell lysis in a microfluidic
      flow environment.

PMID- 29053457
TI  - Partial Deconvolution With Inaccurate Blur Kernel.
AB  - Most non-blind deconvolution methods are developed under the error-free kernel
      assumption, and are not robust to inaccurate blur kernel. Unfortunately, despite
      the great progress in blind deconvolution, estimation error remains inevitable
      during blur kernel estimation. Consequently, severe artifacts such as ringing
      effects and distortions are likely to be introduced in the non-blind
      deconvolution stage. In this paper, we tackle this issue by suggesting: 1) a
      partial map in the Fourier domain for modeling kernel estimation error, and 2) a
      partial deconvolution model for robust deblurring with inaccurate blur kernel.
      The partial map is constructed by detecting the reliable Fourier entries of
      estimated blur kernel. And partial deconvolution is applied to wavelet-based and
      learning-based models to suppress the adverse effect of kernel estimation error.
      Furthermore, an E-M algorithm is developed for estimating the partial map and
      recovering the latent sharp image alternatively. Experimental results show that
      our partial deconvolution model is effective in relieving artifacts caused by
      inaccurate blur kernel, and can achieve favorable deblurring quality on synthetic
      and real blurry images.

PMID- 29053458
TI  - Performance Re-Evaluation on "Codewords Distribution-Based Optimal Combination of
      Equal-Average Equal-Variance Equal-Norm Nearest Neighbor Fast Search Algorithm
      for Vector Quantization Encoding".
AB  - In the re-evaluated paper, Xie et al. proposed a new fast search algorithm for
      vector quantization encoding, which optimized the priority checking order of
      variance and norm inequality in order to speed up the encoding procedure. CPU
      time of different encoding algorithms is given to support their algorithm.
      However, first, some of the experimental data in the re-evaluated paper are
      unreasonable and unrepeatable. And second, as an improved algorithm of equal
      average equal-variance equal-norm nearest neighbor fast search algorithm, the re
      evaluated algorithm in fact cannot achieve a better performance than the existing
      improved equal-average equal-variance nearest neighbor fast search algorithm. In
      this paper, these two problems are analyzed, re-evaluated, and discussed in
      detail.

PMID- 29053459
TI  - A Neurodynamic Approach to Distributed Optimization With Globally Coupled
      Constraints.
AB  - In this paper, a distributed neurodynamic approach is proposed for constrained
      convex optimization. The objective function is a sum of local convex subproblems,
      whereas the constraints of these subproblems are coupled. Each local objective
      function is minimized individually with the proposed neurodynamic optimization
      approach. Through information exchange between connected neighbors only, all
      nodes can reach consensus on the Lagrange multipliers of all global equality and
      inequality constraints, and the decision variables converge to the global optimum
      in a distributed manner. Simulation results of two power system cases are
      discussed to substantiate the effectiveness and characteristics of the proposed
      approach.

PMID- 29053460
TI  - SDL: Saliency-Based Dictionary Learning Framework for Image Similarity.
AB  - In image classification, obtaining adequate data to learn a robust classifier has
      often proven to be difficult in several scenarios. Classification of histological
      tissue images for health care analysis is a notable application in this context
      due to the necessity of surgery, biopsy or autopsy. To adequately exploit limited
      training data in classification, we propose a saliency guided dictionary learning
      method and subsequently an image similarity technique for histo-pathological
      image classification. Salient object detection from images aids in the
      identification of discriminative image features. We leverage the saliency values
      for the local image regions to learn a dictionary and respective sparse codes for
      an image, such that the more salient features are reconstructed with smaller
      error. The dictionary learned from an image gives a compact representation of the
      image itself and is capable of representing images with similar content, with
      comparable sparse codes. We employ this idea to design a similarity measure
      between a pair of images, where local image features of one image, are encoded
      with the dictionary learned from the other and vice versa. To effectively utilize
      the learned dictionary, we take into account the contribution of each dictionary
      atom in the sparse codes to generate a global image representation for image
      comparison. The efficacy of the proposed method was evaluated using three tissue
      data sets that consist of mammalian kidney, lung and spleen tissue, breast
      cancer, and colon cancer tissue images. From the experiments, we observe that our
      methods outperform the state of the art with an increase of 14.2% in the average
      classification accuracy over all data sets.

PMID- 29053461
TI  - Micro-Lens-Based Matching for Scene Recovery in Lenslet Cameras.
AB  - Since a light-field camera is able to capture more information than a traditional
      camera, a lot of methods, such as depth estimation, image super-resolution, and
      view synthesis, are explored for recovering scene information. In this paper, we
      propose a novel framework for scene recovery based on lenslet-based light-field
      camera images. Instead of using traditional matching terms, we design a new micro
      lens-based matching term to calculate structure information and recover several
      kinds of scene information simultaneously. On the one hand, inherent information
      in micro-lens images is selected to complement details in sub-aperture images. On
      the other hand, sub-aperture images are used to expand micro-lens images and
      synthesize new view images. A new micro-lens-based consistency metric is
      introduced for the matching term to handle occlusions in depth estimation and
      image reconstruction. The newly appeared and newly occluded areas in synthesized
      views are analyzed and recovered based on information from surrounding points.
      Experimental results show that the proposed depth estimation method outperforms
      state-of-the-art methods on both synthetic and lenslet-based light-field images,
      especially in low-texture and occlusion regions. Furthermore, the super
      resolution and view synthesis methods are able to acquire view images with more
      details and less aliasing artifacts.

PMID- 29053462
TI  - Implicit Block Diagonal Low-Rank Representation.
AB  - While current block diagonal constrained subspace clustering methods are
      performed explicitly on the original data space, in practice, it is often more
      desirable to embed the block diagonal prior into the reproducing kernel Hilbert
      feature space by kernelization techniques, as the underlying data structure in
      reality is usually nonlinear. However, it is still unknown how to carry out the
      embedding and kernelization in the models with block diagonal constraints. In
      this paper, we shall take a step in this direction. First, we establish a novel
      model termed implicit block diagonal low-rank representation (IBDLR), by
      incorporating the implicit feature representation and block diagonal prior into
      the prevalent low-rank representation method. Second, mostly important, we show
      that the model in IBDLR could be kernelized by making use of a smoothed dual
      representation and the specifics of a proximal gradient-based optimization
      algorithm. Finally, we provide some theoretical analyses for the convergence of
      our optimization algorithm. Comprehensive experiments on synthetic and real-world
      data sets demonstrate the superiorities of our IBDLR over state-of-the-art
      methods.

PMID- 29053463
TI  - Cooperative Fault Tolerant Tracking Control for Multiagent Systems: An
      Intermediate Estimator-Based Approach.
AB  - This paper studies the observer based fault tolerant tracking control problem for
      linear multiagent systems with multiple faults and mismatched disturbances. A
      novel distributed intermediate estimator based fault tolerant tracking protocol
      is presented. The leader's input is nonzero and unavailable to the followers. By
      applying a projection technique, the mismatched disturbances are separated into
      matched and unmatched components. For each node, a tracking error system is
      established, for which an intermediate estimator driven by the relative output
      measurements is constructed to estimate the sensor faults and a combined signal
      of the leader's input, process faults, and matched disturbance component. Based
      on the estimation, a fault tolerant tracking protocol is designed to eliminate
      the effects of the combined signal. Besides, the effect of unmatched disturbance
      component can be attenuated by directly adjusting some specified parameters.
      Finally, a simulation example of aircraft demonstrates the effectiveness of the
      designed tracking protocol.

PMID- 29053464
TI  - Co-expression Network Approach to Studying the Effects of Botulinum Neurotoxin-A.
AB  - Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical
      applications.The goal of this study was to utilize co-expression network theory
      to analyze temporal transcriptional data from skeletal muscle after BoNT-A
      treatment. Expression data for 2000 genes (extracted using a ranking heuristic)
      served as the basis for this analysis. Using weighted gene co-expression network
      analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically
      clustered into 5 groups. Quantifying average expression and co-expression
      patterns across these groups revealed temporal aspects of muscle's response to
      BoNT-A. Functional analysis revealed enrichment of group 1 with metabolism; group
      5 with contradictory functions of atrophy and cellular recovery; and groups 2 and
      3 with extracellular matrix (ECM) and non-fast fiber isoforms. Topological
      positioning of two highly ranked, significantly expressed genes- Dclk1 and
      Ostalpha within group 5 suggested possible mechanistic roles in recovery from
      BoNT-A induced atrophy. Phenotypic correlations of groups with titin and myosin
      protein content further emphasized the effect of BoNT-A on the sarcomeric
      contraction machinery in early phase of chemodenervation. In summary, our
      approach revealed a hierarchical functional response to BoNT-A induced paralysis
      with early metabolic and later ECM responses and identified putative biomarkers
      associated with chemodenervation. Additionally, our results provide an unbiased
      validation of the response documented in our previous workBotulinum Neurotoxin A
      (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of
      this study was to utilize co-expression network theory to analyze temporal
      transcriptional data from skeletal muscle after BoNT-A treatment. Expression data
      for 2000 genes (extracted using a ranking heuristic) served as the basis for this
      analysis. Using weighted gene co-expression network analysis (WGCNA), we
      identified 19 co-expressed modules, further hierarchically clustered into 5
      groups. Quantifying average expression and co-expression patterns across these
      groups revealed temporal aspects of muscle's response to BoNT-A. Functional
      analysis revealed enrichment of group 1 with metabolism; group 5 with
      contradictory functions of atrophy and cellular recovery; and groups 2 and 3 with
      extracellular matrix (ECM) and non-fast fiber isoforms. Topological positioning
      of two highly ranked, significantly expressed genes- Dclk1 and Ostalpha within
      group 5 suggested possible mechanistic roles in recovery from BoNT-A induced
      atrophy. Phenotypic correlations of groups with titin and myosin protein content
      further emphasized the effect of BoNT-A on the sarcomeric contraction machinery
      in early phase of chemodenervation. In summary, our approach revealed a
      hierarchical functional response to BoNT-A induced paralysis with early metabolic
      and later ECM responses and identified putative biomarkers associated with
      chemodenervation. Additionally, our results provide an unbiased validation of the
      response documented in our previous work.

PMID- 29053465
TI  - Automated and Robust Quantification of Colocalization in Dual-Color Fluorescence
      Microscopy: A Nonparametric Statistical Approach.
AB  - Colocalization is a powerful tool to study the interactions between fluorescently
      labeled molecules in biological fluorescence microscopy. However, existing
      techniques for colocalization analysis have not undergone continued development
      especially in regards to robust statistical support. In this paper, we examine
      two of the most popular quantification techniques for colocalization and argue
      that they could be improved upon using ideas from nonparametric statistics and
      scan statistics. In particular, we propose a new colocalization metric that is
      robust, easily implementable, and optimal in a rigorous statistical testing
      framework. Application to several benchmark data sets, as well as biological
      examples, further demonstrates the usefulness of the proposed technique.

PMID- 29053466
TI  - Classification of Single-cell Gene Expression Trajectories from Incomplete and
      Noisy Data.
AB  - This paper studies classification of gene-expression trajectories coming from two
      classes, healthy and mutated (cancerous) using Boolean networks with perturbation
      (BNps) to model the dynamics of each class at the state level. Each class has its
      own BNp, which is partially known based on gene pathways. We employ a Gaussian
      model at the observation level to show the expression values of the genes given
      the hidden binary states at each time point. We use expectation maximization (EM)
      to learn the BNps and the unknown model parameters, derive closed-form updates
      for the parameters, and propose a learning algorithm. After learning, a plug-in
      Bayes classifier is used to classify unlabeled trajectories, which can have
      missing data. Measuring gene expressions at different times yields trajectories
      only when measurements come from a single cell. In multiple-cell scenarios, the
      expression values are averages over many cells with possibly different states.
      Via the central-limit theorem, we propose another model for expression data in
      multiple-cell scenarios. Simulations demonstrate that single-cell trajectory data
      can outperform multiple-cell average expression data relative to classification
      error, especially in high-noise situations. We also consider data generated via a
      mammalian cell-cycle network, both the wild-type and with a common mutation
      affecting p27.This paper studies classification of gene-expression trajectories
      coming from two classes, healthy and mutated (cancerous) using Boolean networks
      with perturbation (BNps) to model the dynamics of each class at the state level.
      Each class has its own BNp, which is partially known based on gene pathways. We
      employ a Gaussian model at the observation level to show the expression values of
      the genes given the hidden binary states at each time point. We use expectation
      maximization (EM) to learn the BNps and the unknown model parameters, derive
      closed-form updates for the parameters, and propose a learning algorithm. After
      learning, a plug-in Bayes classifier is used to classify unlabeled trajectories,
      which can have missing data. Measuring gene expressions at different times yields
      trajectories only when measurements come from a single cell. In multiple-cell
      scenarios, the expression values are averages over many cells with possibly
      different states. Via the central-limit theorem, we propose another model for
      expression data in multiple-cell scenarios. Simulations demonstrate that single
      cell trajectory data can outperform multiple-cell average expression data
      relative to classification error, especially in high-noise situations. We also
      consider data generated via a mammalian cell-cycle network, both the wild-type
      and with a common mutation affecting p27.

PMID- 29053467
TI  - Relaxation dynamics and polydispersivity associated with defects and
      ferroelectric correlations in Ba-doped EuTiO3.
AB  - We present the frequency- and temperature-dependent dielectric response of Eu1-x
      Ba x TiO3 (0  ?  x  ?  0.5) in detail. Excluding grain boundary effects, four
      relaxation mechanisms were observed. Relaxation dynamics were observed to arise
      due to hopping conduction associated with defects, namely oxygen vacancies as
      well as Eu3+ and Ti3+ ions. Dielectric relaxation analysis led to the
      identification of Ti ions in two different environments with different relaxation
      rates in the overall EuTiO3 perovskite structure. The emergence of another
      relaxation mechanism associated with ferroelectric order as a consequence of the
      formation of polar regions was also observed for higher Ba concentrations. The
      addition of Ba led to the identification of relaxation dynamics associated with
      hopping conduction between Eu ions, Ti ions (in the regions with and without
      oxygen vacancies) and with the formation of ferroelectric polar regions.
      Furthermore, the polydispersivity and relaxation times were extracted within the
      framework of the modified Debye model. Relaxation times have been observed to
      increase with a decrease in temperature while larger values of polydispersivity
      reveal a wide distribution of relaxation times due to the presence of lattice
      parameter and energy barrier distributions.

PMID- 29053468
TI  - Monovacancy paramagnetism in neutron-irradiated graphite probed by 13C NMR.
AB  - We report on the magnetic properties of monovacancy defects in neutron-irradiated
      graphite, probed by 13C nuclear magnetic resonance spectroscopy. The bulk
      paramagnetism of the defect moments is revealed by the temperature dependence of
      the NMR frequency shift and spectral linewidth, both of which follow a Curie
      behavior, in agreement with measurements of the macroscopic magnetization.
      Compared to pristine graphite, the fluctuating hyperfine fields generated by the
      defect moments lead to an enhancement of the 13C nuclear spin-lattice relaxation
      rate [Formula: see text] by about two orders of magnitude. With an applied
      magnetic field of 7.1 T, the temperature dependence of [Formula: see text] below
      about 10 K can well be described by a thermally activated form, [Formula: see
      text], yielding a singular Zeeman energy of ([Formula: see text]) meV, in
      excellent agreement with the sole presence of polarized, non-interacting defect
      moments.

PMID- 29053469
TI  - Core to shell switching of the conduction channel on SnO2 nanowire sensors.
AB  - A sensor based on random connections of single-crystalline SnO2 nanowires (NWs)
      has been fabricated for ethanol detection. The NW length of ~10 MUm leads to the
      formation of several random node connections between the Ag electrodes. The
      samples were subjected to thermal treatments under a reducing atmosphere of
      H2/Ar, to generate oxygen vacancies at the surface of the NWs. As a result, the
      core conduction channel of the NWs, where the conduction is based on electron
      hopping through the potential barriers at the contact nodes, switch to the
      surface of the NWs by the creation of an impurity band of shallow donors located
      at 0.347 eV below the conduction band. We suggest that the H2-rich atmosphere of
      the thermal treatments induced the formation of interstitial hydrogen (H i ) and
      substitutional hydrogen (HO), which are shallow donors with low formation energy.

PMID- 29053470
TI  - NbN superconducting nanonetwork fabricated using porous silicon templates and
      high-resolution electron beam lithography.
AB  - Superconducting NbN nanonetworks with a very small number of interconnected
      nanowires, with diameter of the order of 4 nm, are fabricated combining a bottom
      up (use of porous silicon nanotemplates) with a top-down technique (high
      resolution electron beam lithography). The method is easy to control and allows
      the fabrication of devices, on a robust support, with electrical properties close
      to a one-dimensional superconductor that can be used fruitfully for novel
      applications.

PMID- 29053471
TI  - PEGylated anticancer-carbon nanotubes complex targeting mitochondria of lung
      cancer cells.
AB  - Although activating apoptosis in cancer cells by targeting the mitochondria is an
      effective strategy for cancer therapy, insufficient targeting of the mitochondria
      in cancer cells restricts the availability in clinical treatment. Here, we report
      on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that
      improves the mitochondrial targeting of lung cancer cells. The polyethylene
      glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via
      macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal
      escape and delivered into the mitochondria. Cytosol release of the nanodrug led
      to apoptosis of lung cancer cells by abruption of the mitochondrial membrane
      potential, inducing Bcl-2-mediated apoptosis and generating intracellular
      reactive oxygen species. As such, this study provides an effective strategy for
      increasing the anti-lung cancer efficacy by increasing mitochondria accumulation
      rate of cytosol released anticancer nanodrugs.

PMID- 29053472
TI  - Bilayers of Ni3C12S12 and Pt3C12S12: graphene-like 2D topological insulators
      tunable by electric fields.
AB  - In the present work we predict, through first-principles calculations, that
      bilayers of the recently synthesized Ni3 [Formula: see text] [Formula: see text]
      and Pt3 [Formula: see text] [Formula: see text] layered materials are topological
      insulators upon electron doping, and that their topological insulator properties
      can be modulated by the application of electric fields with magnitudes achievable
      in devices. The electronic structures of both bilayers are characterized by spin
      orbit split graphene-like bands, with gap magnitudes that are three orders of
      magnitude larger than graphene's. In ribbon geometries, chiral edge modes develop
      at each side with band dispersions similar to that of Kane-Mele graphene model.
      Surprisingly, the edge states' spin-propagation locking occurs even for very thin
      ribbons. We also find that the response of the electronic structure of both
      materials to applied electric fields are similar to both graphene and the Kane
      Mele model with a Rashba term. All these findings indicate that these bilayer
      systems can be considered as large-spin-orbit graphene analogues with a strong
      sensitivity to applied electric fields.

PMID- 29053473
TI  - Enhancing Raman signals through electromagnetic hot zones induced by magnetic
      dipole resonance of metal-free nanoparticles.
AB  - In this study, we found that the large area of electromagnetic field hot zone
      induced through magnetic dipole resonance of metal-free structures can greatly
      enhance Raman scattering signals. The magnetic resonant nanocavities, based on
      high-refractive-index silicon nanoparticles (SiNPs), were designed to resonate at
      the wavelength of the excitation laser of the Raman system. The well-dispersed
      SiNPs that were not closely packed displayed significant magnetic dipole
      resonance and gave a Raman enhancement per unit volume of 59 347. The hot zones
      of intense electric field were generated not only within the nonmetallic NPs but
      also around them, even within the underlying substrate. We observed
      experimentally that gallium nitride (GaN) and silicon carbide (SiC) surfaces
      presenting very few SiNPs (coverage: <0.3%) could display significantly enhanced
      (>50%) Raman signals. In contrast, the Raman signals of the underlying substrates
      were not enhanced by gold nanoparticles (AuNPs), even though these NPs displayed
      a localized surface plasmon resonance (LSPR) phenomenon. A comparison of the
      areas of the electric field hot zones (E 2 > 10) generated by SiNPs undergoing
      magnetic dipole resonance with the electric field hot spots (E 2 > 10) generated
      by AuNPs undergoing LSPR revealed that the former was approximately 70 times that
      of the latter. More noteworthily, the electromagnetic field hot zone generated
      from the SiNP is able to extend into the surrounding and underlying media.
      Relative to metallic NPs undergoing LSPR, these nonmetallic NPs displaying
      magnetic dipole resonance were more effective at enhancing the Raman scattering
      signals from analytes that were underlying, or even far away from, them. This
      application of magnetic dipole resonance in metal-free structures appears to have
      great potential for use in developing next-generation techniques for Raman
      enhancement.

PMID- 29053474
TI  - Photonic surface waves on metamaterial interfaces.
AB  - A surface wave (SW) in optics is a light wave, which is supported at an interface
      of two dissimilar media and propagates along the interface with its field
      amplitude exponentially decaying away from the boundary. Research on surface
      waves has been flourishing in the last few decades due to their unique properties
      of surface sensitivity and field localization. These features have resulted in
      applications in nano-guiding, sensing, light-trapping and imaging based on near
      field techniques, contributing to the establishment of nanophotonics as a field
      of research. Up to now, a wide variety of surface waves has been investigated in
      numerous material and structure settings. This article reviews the recent
      progress and development in the physics of SWs localized at metamaterial
      interfaces, as well as bulk media in order to provide broader perspectives on
      optical surface waves in general. For each type of surface wave, we discuss the
      material and structural platforms. We mainly focus on experimental realizations
      in the visible and near-infrared wavelength ranges. We also address existing and
      potential application of SWs in chemical and biological sensing, and experimental
      excitation and characterization methods.

PMID- 29053475
TI  - BNC nanoshells: a novel structure for atomic storage.
AB  - Quantum molecular dynamics (QMD) and density functional theory are employed in
      this work in order to study the structural and electronic properties of carbon,
      boron nitride or hybrid BNC nanoshells. The studied nanoshells can be formed by
      stacking two zigzag graphene nanoribbons, two zigzag boron nitride nanoribbons or
      one zigzag graphene nanoribbon on a boron nitride nanoribbon. In all cases only
      one of the edges of the ribbon is passivated, while the other one is left
      unpassivated. Our QMD results show that these nanoribbons collapse just a few
      femtoseconds after the beginning of the simulation, forming a coalesced structure
      in the shape of a shell. Our band structure calculations revealed that this
      structures may be metallic or semiconductor, depending on its stoichiometry.
      Furthermore, a spin splitting for energies near the Fermi level is predicted for
      both the pure carbon and the hybrid BNC-nanoshell systems. We further show that
      when a transverse electric field is applied to these systems, the nanoshell
      structure tends to open up. This effect can lead to the application of these
      nanoshells for molecular storage. As a proof of concept, We investigate this
      storage effect for the H2 molecule.

PMID- 29053476
TI  - Balsam-pear-like rutile/anatase core/shell titania nanorod arrays for
      photoelectrochemical water splitting.
AB  - In this work, a solution combustion followed by dissolution in hydrogen peroxide
      is adopted to achieve a precursor for decorating anatase TiO2 nanosheets along
      single-crystalline rutile TiO2 nanorods, which achieves balsam-pear-like
      core/shell nanorod arrays with enhanced photoelectrochemical water splitting. The
      enhanced photoelectrochemical performance is attributed to the novel
      nanoarchitecture, which can simultaneously offer a high surface area, enhanced
      light-harvesting, a rutile/anatase junction for charge carrier separation and a
      conductive pathway for charge carrier collection. The photoanode design can also
      give hints to other functional materials.

PMID- 29053477
TI  - Revisiting local structural changes in GeO2 glass at high pressure.
AB  - Despite the great importance in fundamental and industrial fields, understanding
      structural changes for pressure-induced polyamorphism in network-forming glasses
      remains a formidable challenge. Here, we revisited the local structural
      transformations in GeO2 glass up to 54 GPa using x-ray absorption fine structure
      (XAFS) spectroscopy via a combination diamond anvil cell and polycapillary half
      lens. Three polyamorphic transitions can be clearly identified by XAFS structure
      refinement. First, a progressive increase of the nearest Ge-O distance and bond
      disorder to a maximum at ~5-16 GPa, in the same pressure region of previously
      observed tetrahedral-octahedral transformation. Second, a marked decrease of the
      nearest Ge-O distance at ~16-22.6 GPa but a slight increase at ~22.6-32.7 GPa,
      with a concomitant decrease of bond disorder. This stage can be related to a
      second-order-like transition from less dense to dense octahedral glass. Third,
      another decrease in the nearest Ge-O distance at ~32.7-41.4 GPa but a slight
      increase up to 54 GPa, synchronized with a gradual increase of bond disorder.
      This stage provides strong evidence for ultrahigh-pressure polyamorphism with
      coordination number  >6. Furthermore, cooperative modification is observed in
      more distant shells. Those results provide a unified local structural picture for
      elucidating the polyamorphic transitions and densification process in GeO2 glass.

PMID- 29053478
TI  - alpha-Lipoic Acid as Adjunctive Treatment for Schizophrenia: An Open-Label Trial.
AB  - PURPOSE/BACKGROUND: Accumulating evidence suggests an involvement of oxidative
      stress in the pathophysiology of schizophrenia. This offers a hypothesis-derived
      therapeutic approach to hinder oxidative damage and its clinical sequelae. alpha
      Lipoic acid (ALA) is a powerful natural antioxidant indicated to treat diabetic
      neuropathy. METHODS/PROCEDURES: In this pilot investigation, we administered ALA
      (100 mg/d) for 4 months, as an adjunct to antipsychotic medication, to 10
      patients with schizophrenia. FINDINGS/RESULTS: We found robust improvement in
      measures of psychopathology (63.9% reduction in Brief Psychiatric Rating Scale
      scores), neurocognitive parameters, extrapyramidal symptoms, and decreased lipid
      peroxidation. IMPLICATIONS/CONCLUSIONS: If larger, double-blind, placebo
      controlled studies confirm these preliminary findings, ALA could prove useful as
      adjunctive therapy for schizophrenia.

PMID- 29053479
TI  - Pancreatic Pseudocyst Due to Acute Valproic Acid Overdose.

PMID- 29053480
TI  - Impact of Moderate-Intensity and Vigorous-Intensity Physical Activity on
      Mortality.
AB  - PURPOSE: Physical activity guidelines recommend at least 150 min of moderate
      intensity physical activity (MPA), 75 min of vigorous-intensity physical activity
      (VPA), or combination of MPA and VPA. However, few epidemiological studies have
      examined whether the general population can derive equal health benefits from MPA
      or VPA. This study examined the associations of different activity intensities
      with mortality. METHODS: In this prospective cohort study, a total of 83,454
      community-dwelling Japanese who answered a questionnaire in 2000-2003 were
      followed for all-cause mortality through 2012. Subjects were classified into four
      groups by physical activity guidelines and also by the proportion of VPA to total
      MVPA, that is, physically inactive, physically active without any VPA (0% VPA),
      and active with some VPA (30% or less) or with more VPA (more than 30%). Hazard
      ratios of all-cause mortality were calculated with adjustment for potential
      confounders including physical activity volume. RESULTS: During 894,718 person
      years of follow-up, 8891 deaths were identified. Compared with physically
      inactive subjects, the adjusted hazard ratios for all-cause mortality were 0.75
      (95% confidence interval, 0.68-0.83), 0.73 (0.65-0.82), and 0.74 (0.62-0.89)
      among men, and 0.71 (0.62-0.81), 0.75 (0.64-0.88), and 0.74 (0.58-0.94) among
      women. For "0% VPA," "30% or less" and "more than 30%," respectively.
      CONCLUSIONS: Meeting the guidelines in either pattern of physical activity is
      important for lowering mortality risk. It may be suggested that people can
      receive comparable health benefit by MPA or VPA as long as they meet the
      guideline.

PMID- 29053481
TI  - Programmed Death Ligand 1 Expression Among 700 Consecutive Endometrial Cancers:
      Strong Association With Mismatch Repair Protein Deficiency.
AB  - OBJECTIVE: This study aims to determine the prevalence of programmed death ligand
      1 (PD-L1) expression in endometrial carcinoma (EC) and determine clinical and
      pathological associations. METHODS: Immunohistochemistry for PD-L1 was performed
      on sections of a triple-core tissue microarray of 700 ECs. Positive PD-L1
      expression, defined as 1% of cells staining positive, was evaluated in tumor and
      stromal compartments. Using age-adjusted logistic regression, we estimated odds
      ratios and 95% confidence intervals for associations between PD-L1 expression
      (overall and by staining compartment) with clinical and tumor characteristics.
      Kaplan-Meier plots and log-rank tests were used to evaluate associations between
      PD-L1 expression and EC-specific survival. RESULTS: PD-L1 expression was observed
      in 100 cases (14.3%), including 27 (3.9%) with expression in tumor cells only, 35
      (5.0%) with expression in both tumor cells and stroma, and 38 (5.4%) with
      expression in stroma only. Expression was observed in ECs of different histologic
      types. Tumors characterized by loss of mismatch repair proteins were
      significantly associated with tumoral PD-L1 expression (P < 0.0001), but not with
      stromal PD-L1 expression. Both tumoral and stromal PD-L1 expressions were
      associated with high-grade endometrioid histology, nonendometrioid histology, and
      lymphovascular space invasion. We observed no significant associations between PD
      L1 expression and EC-specific survival. CONCLUSIONS: PD-L1 is expressed in a
      significant proportion of EC and is associated with mismatch repair deficiency,
      potentially representing a mechanism of tumor immune evasion and a therapeutic
      target in EC.

PMID- 29053482
TI  - Five Presidents and a Secretary.

PMID- 29053483
TI  - Sex-Specific Outcomes After Transcatheter Aortic Valve Replacement: A Review of
      the Literature.
AB  - Transcatheter aortic valve replacement (TAVR) is a safe and effective therapy for
      aortic valve replacement in patients ineligible for or at high risk for surgery.
      However, outcomes after TAVR based on an individual's sex remain to be fully
      elucidated. We searched PUBMED and EMBASE using the keywords: "transcatheter
      aortic valve replacement," "transcatheter aortic valve implantation," "sex
      differences," "gender," "sex characteristics" and collected information on
      baseline features, procedural characteristics, and postprocedural outcomes in
      women. Inclusion/exclusion resulted in 23 publications. Women had less
      preexisting comorbidities than men. Most studies reported better survival in
      women (range of hazard ratio [95% CI] = 0.27 [0.09-0.84] to 0.91 [0.75-1.10]). At
      30 days, women also had more vascular complications (6-20% vs 2-14%) and higher
      bleeding rates (10-44% vs 8-25%). Stroke rates were similar at 30 days (women, 1
      7%; men, 1-5%). This literature review showed better survival in women than men
      after TAVR. However, women had more vascular complications and bleeding; stroke
      rates were similar. These findings may partly be explained by fewer baseline
      comorbidities in women. These results should be interpreted with caution as most
      measures only include unadjusted percentages.

PMID- 29053484
TI  - The Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation at
      Orbitofrontal Cortex in the Treatment of Patients With Medication-Refractory
      Obsessive-Compulsive Disorder: A Retrospective Open Study.
AB  - OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic debilitating
      psychiatric disorder, with significant proportion of patients failing to respond
      with current first-line treatments. The present study assesses the safety and
      effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF
      rTMS) over left-orbitofrontal cortex (Lt-OFC) as a potential augmentation
      strategy in treatment of patients with medication-refractory OCD in real-world
      clinical setting. The present report also aims to examine the factors affecting
      response to rTMS and the durability of effects produced by rTMS over 1 month of
      follow-up period. METHODS: Retrospective review and analysis of clinical case
      files of 25 patients with medication-refractory OCD, all of whom had received 20
      sessions of LF-rTMS over Lt-OFC as part of routine clinical care. A reduction of
      25% and 35% in Yale-Brown Obsessive Compulsive Scale scores was used to determine
      the proportion of partial and complete responders, respectively. RESULTS: There
      was a significant decrease in mean Yale-Brown Obsessive Compulsive Scale score at
      the end of 20 sessions of rTMS compared with baseline (7.04 +/- 5.07; P < 0.001),
      with no further significant change during the subsequent 1-month follow-up period
      (0.20 +/- 1.38; P = 0.47). Thirteen patients (52%) met criteria for partial
      response, of which 11 patients (44%) showed complete response. Furthermore,
      higher number of failed medication trials was found to be significantly
      associated with greater chances of nonresponse to rTMS treatment. CONCLUSIONS:
      There is a role of applying LF-rTMS over Lt-OFC as an augmentation strategy in
      ameliorating clinical symptoms among patients with medication-refractory OCD.

PMID- 29053485
TI  - The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment
      on Cognitive Functions in Patients With Treatment-Resistant Schizophrenia.
AB  - OBJECTIVES: Treatment-resistant schizophrenia (TRS) continues to be a challenge
      in modern psychiatry. Most of these patients have severe neurocognitive deficits.
      Electroconvulsive therapy (ECT) has proved effective and safe in the treatment of
      TRS, but because of potential neurocognitive adverse effects, it is associated
      with many controversies. The aim of this prospective, open study was to evaluate
      the effects of ECT augmentation of antipsychotics on cognitive functions in
      patients with TRS. METHODS: Overall, 31 inpatients with TRS were included, 16
      men, with an average (SD) age of 34.1 (11.187) years. The evaluation of clinical
      symptoms and global impression, as well as verbal memory, visual memory, working
      memory, psychomotor speed, verbal fluency, and executive functioning, was
      conducted before and after the completion of ECT treatment. RESULTS: We ran a
      series of paired-samples t tests, and the Bonferroni adjustment for multiple
      comparisons reduced the significance level to P = 0.004. The neurocognitive
      domains that demonstrated statistically significant improvement were immediate
      and delayed verbal memory, and executive functioning, whereas statistical trend
      was observed for visual memory and psychomotor speed. None of the neurocognitive
      functions exhibited significant deterioration after the ECT treatment.
      Electroconvulsive therapy was effective in reducing general symptoms of
      schizophrenia, resulting in more than 30% decrease in the overall symptom
      severity measured by the Positive and Negative Syndrome Scale. CONCLUSIONS:
      Notwithstanding some limitations of this study, the combination of ECT and
      antipsychotics has improved several neurocognitive domains, without evidence of
      worsening of any cognitive functions.

PMID- 29053486
TI  - Retrospective Analysis of Sinus Membrane Thickening: Profile, Causal Factors, and
      Its Influence on Complications.
AB  - PURPOSE: To retrospectively determine the profile of the sinus membrane (SM),
      potential factors affecting SM thickening (SMT), and the correlation between SMT
      and sinus augmentation (SA) complications. MATERIALS AND METHODS: In the patients
      who received lateral SA, SMT was classified in sagittal sections of cone-beam
      computed tomography according to its thickness and morphology. The correlation
      between SMT and the following factors was analyzed: age, sex, endodontic and
      periodontic statuses of neighboring teeth, and shape of the sinus inferior
      border. The association between SMT and SA complications was investigated.
      RESULTS: SMT of <=2 mm was prevalent (60%). Irregular SM was mostly observed for
      SMT of >2 mm. There was no statistically significant association between SMT and
      the included factors. SMT did not significantly correlate with either perforation
      or postoperative complications. There was a statistically significant increase in
      implant failure when SMT was >2 mm, but it was hard to determine that the failure
      was solely affected by SMT. CONCLUSION: SMT was not influenced by the factors
      included in this study, and it might not be a risk factor for SA and implant
      failure.

PMID- 29053487
TI  - Effect of Experimental Conditions in the Accommodation Response in Myopia.
AB  - SIGNIFICANCE: The accommodative response is more affected by the type of
      refractive error than the method of stimulation, field of view (FOV), or stimulus
      depth. PURPOSE: This study aims to analyze the effect of stimulation method,
      stimulus depth, and FOV on the accommodation response (AR) for emmetropes (EMM),
      late-onset myopes (LOM), and early-onset myopes (EOM). METHODS: Monocular AR was
      measured in 26 young observers (n = 9 EMM, n = 8 LOM, n = 9 EOM) under 60
      different viewing conditions that were the result of permuting the following
      factors: (1) stimulation method (free space or Badal lens viewing), (2) stimulus
      depth (flat or volumetric), (3) FOV (2.5, 4, 8, 10, and 30 degrees ), and (4)
      accommodative stimulus (AS: 0.17, 2.50, and 5.00 diopters [D]). RESULTS: Mixed
      analysis of variance for 2.50 D of AS resulted in a significant effect of
      refractive group (F = 6.77, P < .01) and FOV (F = 1.26, P = .04). There was also
      a significant interaction between stimulus depth and FOV (F = 2.73, P = .03) and
      among stimulation method, FOV, and refractive group (F = 2.42, P = .02). For AS
      of 5.00 D, there was a significant effect of refractive group (F = 13.88, P <
      .01) and stimulation method (F = 5.16, P = .03). There was also a significant
      interaction of stimulation method, stimulus depth, and refractive group (F =
      4.08, P = .03). When controlling for all interactions, LOM showed larger lags
      than EMM and EOM; the AR did not significantly change for fields of 8, 10, and 30
      degrees , and it did not significantly differ for different stimulation methods
      or stimulus depth. CONCLUSIONS: Previously reported differences in AR when using
      lens-based methods compared with free space viewing may be explained by the
      effect of other factors such as the FOV or the depth of the stimulus. Targets
      with an FOV of 8 or 10 degrees  may be optimal for accurate ARs.

PMID- 29053488
TI  - Causes of Childhood Vision Impairment in the School for the Blind in Eritrea.
AB  - SIGNIFICANCE: Our study provides the much-needed evidence on causes of childhood
      blindness in Eritrea. This will assist authorities to plan appropriate strategies
      and implement preventive, curative, and rehabilitative services to address these
      causes of vision loss in children in this resource-limited country. PURPOSE: This
      study aims to identify the causes of severe vision impairment and blindness in
      children attending the only school for the blind in Eritrea. METHODS: All
      children enrolled in the school were examined, and the World Health Organization
      form for the examination of visually impaired children was used to record the
      data. Examination included visual acuity, refraction, anterior segment, and
      fundus assessment. Causes of vision loss for children with severe vision
      impairment (visual acuity <6/60 to 3/60) and blindness (visual acuity <3/60) are
      reported. Causes were classified by the anatomical site affected and by
      underlying etiology based on the timing of the insult and causal factor. RESULTS:
      A total of 92 children were examined, and 71 (77.2%) of them had severe vision
      impairment and blindness. The major causes of vision loss were corneal scars
      (16.9%), cataract (12.7%), phthisis bulbi (11.3%), congenital eye deformities
      (11.3%), optic atrophy (9.3%), and presumed chorioretinal Toxoplasma scars
      (7.0%). Hereditary factors were the major known etiological category (15.5%)
      followed by the sequel of eye injuries (12.7%). Blindness due to vitamin A
      deficiency was not found, whereas infectious causes such as measles and
      ophthalmia neonatorum were relatively absent (one case each). Potentially
      avoidable causes of vision impairment were accounted for in 47.9% of children.
      CONCLUSIONS: This study provides the first direct evidence on childhood vision
      impairment in Eritrea. Despite the limitations, it is clearly shown that nearly
      half of the vision loss is due to avoidable causes. Thus, preventive public
      health strategies, specialist pediatric eye care, and rehabilitative services are
      recommended to address childhood vision impairment in Eritrea.

PMID- 29053489
TI  - The More Things Change, the More They Stay the Same: A Study to Evaluate
      Compliance With Inclusion and Assessment of Women and Minorities in Randomized
      Controlled Trials.
AB  - PURPOSE: The National Institutes of Health (NIH) Revitalization Act of 1993
      requires NIH-funded clinical trials to include women and minorities as
      participants and assess outcomes by sex and race or ethnicity. The objective of
      this study was to investigate current levels of compliance with these guidelines
      for inclusion, analysis, and reporting in NIH-funded randomized controlled trials
      (RCTs) and compare the results with those from 2009 and 2004, which the authors
      reported previously. METHOD: The authors identified 782 RCTs published in 14
      leading U.S. medical journals in 2015 with a PubMed search. Of those, 142 were
      the primary report of an NIH-funded RCT, conducted in the United States, and
      eligible for analysis. The authors reviewed abstract, text, and tables of each
      eligible study as well as any follow-up published commentary to determine
      compliance with NIH guidelines. RESULTS: Thirty-five studies limited enrollment
      to one sex. The median enrollment of women in the remaining 107 studies was 46%,
      but 16 (15.0%) enrolled less than 30% women. Twenty-eight of the 107 (26%)
      reported at least one outcome by sex or explicitly included sex as a covariate in
      statistical analysis. Of the 142 studies, 19 (13.4%) analyzed or reported
      outcomes by race or ethnicity. There were no statistically significant changes in
      inclusion, analysis, or reporting by sex, race, or ethnicity compared with the
      previous studies. CONCLUSIONS: NIH policies have not resulted in significant
      increases in reporting results by sex, race, or ethnicity. The authors recommend
      strong journal policies to increase compliance with NIH policies.

PMID- 29053490
TI  - PAEA Accreditation Task Force Briefing Paper: Moving Toward Profession-Defined,
      Outcomes-Based Accreditation.
AB  - In anticipation of a revision to the Standards for Accreditation, the Phyisician
      Assistant Education Association (PAEA) charged a small task force to develop a
      strategy for engaging its members in the revision process. Rather than focusing
      on the current Standards, the task force members recommend a backward design
      approach to determine the desired outcomes of a successful revision to the
      Standards. Ultimately, the group believes that shifting to a profession-defined,
      outcomes-based model for accreditation will allow for greater innovation in
      physician assistant education and reduce the strain on programs facing resource
      limitations, particularly clinical site shortages. Task force members value
      accreditation and urge a paradigm shift in the Standards revision process to
      focus on meaningful educational outcomes that lead to enhanced program quality
      and patient safety.

PMID- 29053491
TI  - Safety and Feasibility of Early Physical Therapy for Patients on Extracorporeal
      Membrane Oxygenator: University of Maryland Medical Center Experience.
AB  - OBJECTIVES: To examine the feasibility and safety of mobilizing patients while on
      extracorporeal membranous oxygenation support. DESIGN: Retrospective cohort
      study. SETTING: Medical and Surgical ICUs in a large tertiary care hospital in
      the United States. PATIENTS: Adults supported on extracorporeal membranous
      oxygenation from January 2014 to December 2015. MEASUREMENTS AND MAIN RESULTS: We
      reviewed the medical records from physical therapy, perfusion, and intensivists
      to obtain the number and type of physical therapy interventions and discharge
      status; extracorporeal membranous oxygenation type and description of support,
      cannulation sites; and risk management details of adverse effects, if any. Of 254
      patients supported on extracorporeal membranous oxygenation, 167 patients (66.7%)
      received a total of 607 physical therapy sessions while on extracorporeal
      membranous oxygenation support. In this cohort, 134 patients (80.2%) had at least
      one femoral cannula during physical therapy intervention. Sixty-six of the 167
      patients (39.5%) were supported on extracorporeal membranous oxygenation with
      bifemoral cannulas, and 44 (26.3%) were on veno-arterial extracorporeal
      membranous oxygenation. A dual lumen catheter was only used in five cases. Twenty
      five patients (15%) (13 bifemoral cases) participated in standing or ambulation
      activities. Seventy-five patients (68.8%) who were successfully weaned from
      extracorporeal membranous oxygenation were discharged to a rehabilitation
      facility; 26 patients (23.8%) went home. Three minor events (< 0.5%) involving
      two episodes of arrhythmias and a hypotension event interrupted the therapy
      sessions, but mobility activities and exercises resumed that day. No major events
      were reported. CONCLUSIONS: With a highly trained multidisciplinary team and a
      focus on restoring function, it is feasible and safe to deliver early
      rehabilitation including standing and ambulation to patients on extracorporeal
      membranous oxygenation support even those with femoral cannulation sites with
      veno-arterial extracorporeal membranous oxygenation and veno-venous
      extracorporeal membranous oxygenation.

PMID- 29053492
TI  - Significance of Mini Bronchoalveolar Lavage Fluid Amylase Level in Ventilator
      Associated Pneumonia: A Prospective Observational Study.
AB  - OBJECTIVES: Aspiration of oropharyngeal or gastric contents in intubated patients
      can lead to ventilator-associated pneumonia. Amylase in respiratory secretion has
      been reported as a possible marker of aspiration. We studied whether elevated
      alpha-amylase in mini bronchoalveolar lavage specimens can be suggestive of
      ventilator-associated pneumonia in intubated patients with high clinical
      suspicion. DESIGN: Prospective single-center observational study. SETTING:
      Department of Critical Care Medicine, tertiary care academic institute. PATIENTS:
      Adult patients on mechanical ventilation for more than 48 hours with with
      clinically suspected ventilator-associated pneumonia as per defined criteria,
      admitted between December 2014 and May 2016. METHODS: Mini bronchoalveolar lavage
      samples were collected within 72 hours of endotracheal intubation. Samples were
      sent for alpha-amylase level assay and quantitative culture. Ventilator
      associated pneumonia was confirmed from mini bronchoalveolar lavage microbial
      culture of greater than or equal to 10 cfu/mL, and patients were divided into
      ventilator-associated pneumonia and no ventilator-associated pneumonia groups.
      Pre- and postintubation risk factors for aspiration were also noted. RESULTS: The
      prevalence of ventilator-associated pneumonia was 64.9% among 151 patients in
      whom it was clinically suspected. Median (interquartile range) mini
      bronchoalveolar lavage alpha-amylase levels in ventilator-associated pneumonia
      and no ventilator-associated pneumonia groups on the day of study inclusion were
      287 U/L (164-860 U/L) and 94 U/L (59-236 U/L), respectively (p < 0.001). Median
      (interquartile range) alpha-amylase levels in patients with 0, 1, 2, and 3
      preintubation risk factors were 65 U/L (35-106 U/L), 200 U/L (113-349 U/L), 867
      U/L (353-1,425 U/L), and 3,453 U/L (1,865-4,304 U/L), respectively (p < 0.001)
      and 472 U/L (164-1,452 U/L) and 731 U/L (203-1,403 U/L) in patients with 1 and 2
      postintubation risk factors, respectively (p < 0.001). A mini bronchoalveolar
      lavage alpha-amylase of 163 U/L or more yielded sensitivity and specificity of
      73% and 68.6%, respectively, with area under the receiver operating
      characteristic curve of 0.746 (95% CI, 0.66-0.83). CONCLUSIONS: Patients with
      ventilator-associated pneumonia within 72 hours from intubation have
      significantly elevated alpha-amylase concentrations in mini bronchoalveolar
      lavage fluid. Mini bronchoalveolar lavage alpha-amylase concentrations increase
      with increasing number of aspiration risk factors.

PMID- 29053493
TI  - Induction of Desmoplastic Trichoepithelioma in a Dermatofibroma.
AB  - Induction of follicular germinative structures above a dermatofibroma (DF) is a
      common finding. Rarely, induction of a trichoblastoma in a DF has been observed.
      Here, we report the case of a desmoplastic trichoepithelioma induced by a DF. The
      lesion with clinical and histological appearance of a DF situated on the left
      dorsal foot showed an associated adnexal proliferation that fulfilled
      histopathological criteria of desmoplastic trichoepithelioma.
      Immunohistochemistry (Ber-EP4, Bcl-2, CK17, CK20, CK7, EMA, and Ki67) helped to
      confirm the diagnosis and to exclude possible differential diagnoses.

PMID- 29053494
TI  - Is Immunohistochemical Screening of Cutaneous Leiomyomas for the Early Detection
      of Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome Justified?

PMID- 29053495
TI  - Painful Skin Nodule on the Finger of a 59 Year Old.

PMID- 29053496
TI  - Pearls and Pitfalls in Pediatric Orthopaedic Trauma: The Community Orthopaedic
      Surgeon Taking Trauma Call.

PMID- 29053497
TI  - The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Phalangeal
      Fracture Pearls and Pitfalls.
AB  - Pediatric phalangeal fractures are extremely common, especially among toddlers
      and older children/adolescents involved in sporting activities. The physical
      examination must include an assessment for deviation and malrotation. In
      addition, concomitant injuries must be assessed for such as tendon and/or
      neurovascular injuries. Plain radiographs are typically sufficient to make the
      diagnosis and determine the treatment. The majority of pediatric and adolescent
      phalangeal fractures can be treated with immobilization. Substantial deviation
      and malrotation must be addressed with closed reduction techniques with or
      without percutaneous pinning. Open reduction is reserved for cases with
      concomitant injuries, open fractures, older adolescents, and patients in whom an
      adequate closed reduction cannot be obtained. When diagnosed and treated
      appropriately, pediatric and adolescent phalangeal fractures typically result in
      excellent outcomes.

PMID- 29053498
TI  - The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Forearm Shaft
      Fracture Pearls and Pitfalls.
AB  - Pediatric forearm shaft fractures are the third most common fracture in children,
      and the forearm is the third most mobile joint in the body (with a nearly 180
      degree arc of motion). The goals of treatment are aimed squarely at achieving
      satisfactory anatomic alignment (within defined parameters) as the consequences
      of malunion can be permanent forearm stiffness and deformity. Nonoperative
      treatment approaches still dominate care of the youngest age groups while
      surgical intervention has become increasingly common in older children. This
      article will offer evidence and experience-based tips intended to benefit the
      community orthopedic surgeon caring for children during the course of their on
      call duties.

PMID- 29053499
TI  - The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Supracondylar
      Humeral Fracture Pearls and Pitfalls.
AB  - Supracondylar humeral fractures are the most common type of pediatric elbow
      fracture. With proper treatment, these injuries usually heal well and the
      patients return to full function. However, a small percentage of these injuries
      may result in devastating complications and, thus, provoke anxiety in many
      surgeons treating them. This article provides tips for successful management of
      these injuries without complications and provides references for further study.

PMID- 29053500
TI  - The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Femoral Shaft
      Fracture Pearls and Pitfalls.
AB  - Pediatric femoral shaft fractures present many challenging patient care
      decisions. Nonoperative treatment approaches still dominate care of the youngest
      age groups while surgical intervention is commonplace in virtually all older
      children. Treatment is determined primarily by patient age as modified by
      clinical factors including mechanism of injury, weight, and skeletal maturity.
      Infants can be successfully treated by placement into a Pavlik harness, whereas
      children younger than 5 years are most commonly treated by early reduction and
      spica cast immobilization. Children aged up to 11 years are most commonly treated
      by flexible intramedullary nailing, whereas older children and adolescents,
      particularly with length unstable fractures should be treated with more rigid
      fixation such as lateral entry locked nails or submuscular plating.

PMID- 29053501
TI  - The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Tibia Fracture
      Pearls and Pitfalls.
AB  - Tibial fractures in children present a wide array of challenges to the managing
      orthopaedic surgeon. Injuries cover a spectrum from subtle tibial spine fractures
      to comminuted high-energy shaft fractures requiring free flap coverage.
      Significant risks range from malunion and leg length discrepancy to infected
      nonunions and Volkmann ischemic contracture. This article offers evidence and
      experience-based advice that is aimed at helping the community orthopaedic
      surgeon taking call.

PMID- 29053502
TI  - The Community Orthopaedic Surgeon Taking Trauma Call: Pediatric Ankle Fracture
      Pearls and Pitfalls.
AB  - Pediatric ankle fractures are common and have unique fracture characteristics
      because of the presence of distal tibial and fibular physes. When displaced (>3
      mm widening of the physis or >2 mm intra-articular gap/step-off), these fractures
      are typically treated with anatomical reduction and internal fixation. Computed
      tomography is recommended for preoperative evaluation and surgical planning for
      intra-articular fractures. These fractures in younger children with substantial
      growth remaining should be followed closely to monitor for any growth
      disturbance. Pearls and pitfalls related to the treatment of these fractures
      would emphasize the physeal-respecting approach to their management.

PMID- 29053503
TI  - Lenalidomide-Associated Thyroid-Related Eyelid Retraction.
AB  - Several antineoplastic treatments have been responsible for thyroid dysfunction
      and thyroid eye disease. Min, Vaidya, and Becker (2011) reported a case of
      euthyroid Graves orbitopathy after treatment with ipilimumab with the patient
      displaying proptosis and myositis in the setting of normal thyroid function tests
      and elevated thyroid antibodies. The authors report a case of a 76-year-old woman
      who developed right upper lid retraction and proptosis after 2.5 years of
      treatment with lenalidomide for multiple myeloma. Thyroid function tests were
      normal: thyroid-stimulating hormone 0.808 mIU/mL, total T3 102 ng/dL, free T4
      1.48 ng/dL. Thyroid antibodies were elevated: thyrotropin receptor antibody 2.26
      IU/L, thyroglobulin antibody 1043.1 IU/mL, and thyroid peroxidase antibody 38
      IU/mL. A nuclear medicine thyroid scan was normal. Given the possible thyroid
      effects from lenalidomide, patients who receive this medication should be
      periodically evaluated for thyroid dysfunction and thyroid eye disease.

PMID- 29053504
TI  - Anesthesia and Analgesia Practice Pathway Options for Total Knee Arthroplasty: An
      Evidence-Based Review by the American and European Societies of Regional
      Anesthesia and Pain Medicine.
AB  - In 2014, the American Society of Regional Anesthesia and Pain Medicine in
      collaboration with the European Society of Regional Anaesthesia and Pain Therapy
      convened a group of experts to compare pathways for anesthetic and analgesic
      management for patients undergoing total knee arthroplasty in North America and
      Europe and to develop a practice pathway. This review is intended to be an
      analysis of the current literature to assist individuals and institutions in
      designing a pathway for total knee arthroplasty that is based on existing
      evidence and expert recommendation and may be customized according to individual
      settings.

PMID- 29053505
TI  - The Clinical Benefits of Ultrasound-Guided Thoracic Epidural Placement.

PMID- 29053506
TI  - Reply to Dr Costache et al.

PMID- 29053507
TI  - Ultrasound-Guided Greater Occipital Nerve Block at the C2 Level: A Novel
      Technique?

PMID- 29053508
TI  - Reply to Dr Kastler.

PMID- 29053509
TI  - A Good SOS(nB) Is Also Good for Your OSS.

PMID- 29053510
TI  - Reply to Dr Stimpson et al.

PMID- 29053511
TI  - Decreasing the Incidence of Tuohy-Borst Clamp Connector Disconnections From
      Perineural Catheters: A Quality Improvement Study.

PMID- 29053512
TI  - Incidence of Clinically Overt Hematoma Formation Following Removal of Adductor
      Canal Catheters During Concomitant Factor Xa Inhibitor Therapy.

PMID- 29053513
TI  - Coming of Age for "Green" Anesthesia: The Leading Role of Regional Anesthesia.

PMID- 29053514
TI  - "Everybody-Knows-isms" and Unloading the Dice: A Reply to Drs YaDeau and Liguori.

PMID- 29053515
TI  - Multiple Tissue Expansion for Giant Congenital Melanocytic Nevus.
AB  - OBJECTIVE: Tissue expansion is the preferred technique for the treatment of giant
      congenital melanocytic nevus (GCMN) located on the face, abdomen, and legs. We
      believe that the use of multiple tissue expanders in the same surgery is a safe
      and effective technique for the treatment of GCMN. MATERIALS AND METHODS: A total
      of 14 patients were treated between 2013 and 2016 for GCMN removal with placement
      in the same surgery of 3 or more tissue expanders. We analyzed esthetic results
      and complications. RESULTS: The locations of the GCMN on the 14 patients were on
      the abdomen, thigh, and shoulder. The number of tissue expanders placed was 3 in
      5 patients, 4 in 6 patients, 5 in 1 patient, and 6 in 2 patients. The average
      stay was 4.29 days (1-9 days), and the average time until the removal of the
      expanders was 84.71 days (47-127 days). Only 2 patients had postoperative
      complications, with one having dehiscence of the surgical wound and the other an
      infection of the expander. CONCLUSIONS: The use of multiple tissue expanders for
      GCMN is a safe technique that reduces the number of surgical interventions,
      achieving a total excision of the nevus in less time and at a younger age. The
      esthetic results are similar, and we have not observed a higher rate of
      complications.

PMID- 29053517
TI  - Total Palatal Mobilization and Multilamellar Suturing Technique Improves Outcome
      for Palatal Fistula Repair.
AB  - BACKGROUNDS: The success rate of the surgical repair of palatal fistula after
      palatoplasty is often unsatisfactory. This study is a review of 15 years of
      single surgeon's experience with the evolution of a reliable surgical technique
      with high success rate. METHODS: This is a retrospective chart review of
      consecutive cleft cases undergoing repair of palatal fistula from 2000 to 2015.
      The study included 37 consecutive fistula repair cases with wide elevation and
      mobilization of the palatal tissues and nasal and oral layer repair. Group 1 (n =
      20) were treated earlier in the study using either midline, von Langenbeck, or 2
      flap palatoplasty with 3-layer suturing. Group 2 (n = 17) were treated through a
      Dorrance-type incision and additional repair of the oral periosteum for a total
      of 4-layer suturing. RESULTS: The overall fistula closure rate was 94.6% (90% in
      group 1 and 100% in group 2). The difference in outcome between the 2 groups was
      statistically insignificant (P > 0.05). Most patients (83.8%) had concomitant
      velar muscle retropositioning for treatment of velopharyngeal incompetence.
      CONCLUSIONS: Fistula repair using wide mobilization of the entire palate through
      previous repair incisions and multilamellar suturing technique has a very low
      fistula recurrence rate. Addition of the fourth layer of suturing and the use of
      a Dorrance-type incision further improves the outcome. This approach provides
      wide tissue release and access to tissue layers for better repair and tension
      free closure. Combining intravelar veloplasty with fistula repair is safe and
      allows management of the fistula and its possible consequences on palatal
      function in a single procedure.

PMID- 29053516
TI  - Fat Graft Survival After Recipient Site Pretreatment With Fractional Carbon
      Dioxide Laser.
AB  - BACKGROUND: Fat grafting is a commonly performed procedure not only for
      augmenting the soft tissue but also for regeneration in esthetic and
      reconstructive plastic surgery.However, unpredictable fat survival rate because
      of high resorption rate is remained as the main problem. The purpose of this
      study was to investigate the effect of pretreatment of the recipient site to the
      fat survival using fractional carbon dioxide (CO2) laser. METHODS: The rats were
      divided to 2 groups. Inguinal fat pads of rats were transplanted to the dorsum
      without pretreatment in the control group. The study group was preconditioned by
      fractional CO2 laser to the recipient site 1 week before fat graft.The pulse
      energy was set to 100 mJ. Transplanted fat tissues were harvested at
      postoperative days 1, 3, 7, 14, and 28 and were analyzed morphologically,
      histologically, and immunohistochemically. RESULTS: Weight and volume in the
      control group was more decreased than in the study group at postoperative day 28.
      Histological evaluation showed less inflammation, less fibrosis, less
      vacuolization, and better integrity of adipocytes. Immunohistologically,
      microvessel density in the study group was higher than in the control group (P <
      0.05) at postoperative day 1. Survival rate in the study group was higher than in
      the control group at postoperative days 1, 3, 7, and 14 (P < 0.05). CONCLUSIONS:
      Pretreatment of recipient site using fractional CO2 laser helped vascularization
      in the early stage in fat graft and solved the ischemic condition, so it improved
      fat survival rate.

PMID- 29053518
TI  - Role of Homeodomain-Interacting Protein Kinase 2 in the Pathogenesis of Tissue
      Fibrosis in Keloid-Derived Keratinocytes.
AB  - Epithelial-mesenchymal transition (EMT) plays a critical role in fibrotic keloid
      formation, which is characterized by excessive collagen and extracellular matrix
      synthesis and deposition. Growing evidence suggests that the serine/threonine
      kinase homeodomain-interacting protein kinase 2 (HIPK2) acts upstream of several
      major fibrosis signaling pathways; however, the role of HIPK2 in the keloid
      fibrogenesis remains unknown. In the current study, we investigated the roles of
      HIPK2 in the pathogenesis of keloids. Primary normal skin and keloid
      keratinocytes were cultured and pretreated with transforming growth factor (TGF)
      beta1. Next, keratinocytes were transfected with scrambled small interfering RNA
      (siRNA) and anti-HIPK2 siRNA. The TGF-beta1-associated HIPK2 alterations were
      investigated by quantitative real-time polymerase chain reaction. Protein levels
      were analyzed by western blotting. The HIPK2 was markedly increased in the keloid
      derived keratinocytes compared with normal skin keratinocytes. In addition, HIPK2
      induced the expression of EMT markers in normal skin keratinocytes by TGF-beta1
      SMAD family member 3 (SMAD3). The effect of TGF-beta1-related EMT markers and
      SMAD3 phosphorylation in response to added TGF-beta1 was significantly abrogated
      when the cells were transfected with HIPK2 siRNA. We conclude that HIPK2 is a
      crucial factor in the pathogenesis of keloids, suggesting that HIPK2 might be a
      novel potential drug target for antikeloid therapy.

PMID- 29053519
TI  - A Low-Cost Simulator for Training in Endoscopic-Assisted Transaxillary Dual-Plane
      Breast Augmentation.
AB  - BACKGROUND: Endoscopic-assisted transaxillary dual-plane (EATD) technique is a
      popular procedure for breast augmentation, especially for Chinese women. However,
      frustration is often expressed by plastic surgeons when first attempting EATD
      surgery. Simulation-based teaching is beneficial for EATD training, but it is
      expensive. This study presents a low-cost simulator to help plastic surgeons
      exercise psychomotor skills during EATD surgery. METHODS: The low-cost simulator
      was invented by Dr Jie Luan (the senior author) and made of some easily available
      materials including a mannequin, a T-shirt printed the bottom anatomical
      structure of the chest, the order of dissection, and the potential bleeding spot,
      and an elastic compression garment printed the upper anatomical structure and the
      cut-off position to sever the pectoralis major muscle. The first-year residents
      of plastic surgery assessed their improvement by completing a 5-item evaluation
      questionnaire at the beginning and at the end of the simulation. RESULTS: Fifty
      participants enrolled in this study. There was a significant difference (P <
      0.05) before and after the training regarding candidate confidence, anatomical
      awareness, and endoscope control including the dexterity and hand-to-eye
      coordination. CONCLUSIONS: The low-cost and simple maintenance simulator may help
      plastic surgeons, especially those in developing countries, to improve gradually
      their EATD breast augmentation skills with no risks in a way. Further randomized
      controlled trials are needed to test its validity and reliability.

PMID- 29053520
TI  - Plastic Surgery Management of Victims of Terrorist Violence in Ankara, Turkey.
AB  - Terror attacks have been progressively increasing worldwide through the present
      era. The management of the consequences of terrorism events is under debate in
      almost every scientific area. The organization and advancement of health services
      constitute important components of the crisis management. Similar to other
      specialty areas in medicine, the medical management of terrorist attacks is
      becoming important in terms of plastic and reconstructive surgery.Ankara, the
      capital of Turkey, has been subject to 2 terrorist events in public places within
      a year. The total number of patients involved in both cases was 434. Ankara
      Numune Training and Research Hospital is a tertiary health care institution and
      one of the most important trauma centers in the region. A total of 178 Patients
      exposed to these events referred to our hospital. Of the total, 34 patients were
      completely or partially treated in the plastic and reconstructive surgery clinic.
      In this study, we tried to discuss the difficulties encountered in the
      classification of patients and plastic surgery during the treatment period of
      patients who experienced these attacks.Data were obtained from The National News
      Agency, hospital, and our own clinic registries. Patient classification was based
      on the injured parts of the body. Statistical analysis was performed for all
      data. In conclusion, the role and the importance of plastic surgery department
      especially in trauma management have been emphasized in the light of our
      findings.

PMID- 29053521
TI  - Smartphone-Based Patient Education in Plastic Surgery.
AB  - BACKGROUND: Internet use for health information has dramatically increased in the
      past decade. Mobile medical applications (MMAs) could be a useful tool to improve
      postoperative patient education and care. The objective of this study is to
      evaluate the impact of an MMA on patient care in plastic surgery. METHODS: An MMA
      was developed to improve postoperative plastic surgery patients care. All
      patients who underwent surgery at our plastic surgery department between August
      and November 2014 and were willing to download the MMA were included. Two to 4
      weeks after the procedure, the patients were asked to fill a questionnaire that
      assessed the content, design, and efficacy of the application. RESULTS: Sixty
      patients were included. The patients reported that their questions regarding the
      postoperative management were addressed by the application with a mean score of
      4.1 over 5. Most patients would recommend the application to other plastic
      surgery patients with a mean score of 4.6 over 5. The application prevented 12
      patients (20%) from calling the plastic surgeon or the emergency department.
      CONCLUSIONS: A smartphone application can optimize the plastic surgery patient
      care. It can provide additional information allowing the patients to get involved
      in their own medical care.

PMID- 29053523
TI  - Enhanced Informed Consent in Hand Surgery: Techniques to Improve the Informed
      Consent Process.

PMID- 29053522
TI  - Immediate Enhancement of Nerve Function Using a Novel Axonal Fusion Device After
      Neurotmesis.
AB  - BACKGROUND: The management of peripheral nerve injuries remains a large challenge
      for plastic surgeons. With the inability to fuse axonal endings, results after
      microsurgical nerve repair have been inconsistent. Our current nerve repair
      strategies rely upon the slow and lengthy process of axonal regeneration (~1
      mm/d). Polyethylene glycol (PEG) has been investigated as a potential axonal
      fusion agent; however, the percentage of axonal fusion has been inconsistent. The
      purpose of this study was to identify a PEG delivery device to standardize
      outcomes after attempted axonal fusion with PEG. MATERIALS AND METHODS: We used a
      rat sciatic nerve injury model in which we completely transected and repaired the
      left sciatic nerve to evaluate the efficacy of PEG fusion over a span of 12
      weeks. In addition, we evaluated the effectiveness of a delivery device's ability
      to optimize results after PEG fusion. RESULTS: We found that PEG rapidly (within
      minutes) restores axonal continuity as assessed by electrophysiology, fluorescent
      retrograde tracer, and diffusion tensor imaging. Immunohistochemical analysis
      shows that motor axon counts are significantly increased at 1 week, 4 weeks, and
      12 weeks postoperatively in PEG-treated animals. Furthermore, PEG restored
      behavioral functions up to 50% compared with animals that received the criterion
      standard epineurial repair (control animals). CONCLUSIONS: The ability of PEG to
      rapidly restore nerve function after neurotmesis could have vast implications on
      the clinical management of traumatic injuries to peripheral nerves.

PMID- 29053524
TI  - Nursing Humanities: Teaching for a Sense of Salience.
AB  - Reports have indicated that nursing programs in the United States are not
      generally effective in teaching nursing science, natural science, the social
      sciences, and the humanities. The value of the lifelong study of humanities for
      nurses is the invitation for contemplation on the human experience so we can make
      informed moral, spiritual, and intellectual sense of the world. In essence, when
      we understand, we become more empathetic. This article adds to the call for
      teaching for a sense of salience in nursing through the meaningful synthesis of
      humanities in baccalaureate education.

PMID- 29053525
TI  - Transforming Nursing Education: A Call for a Conceptual Approach.
AB  - In an effort to meet the changing landscape of the health care system and the
      explosion of nursing knowledge, the Institute of Medicine and the Robert Wood
      Johnston Foundation have summoned nursing academia to partner on curriculum
      development with an emphasis on the professional socialization of the new nurse.
      As health care continues to change, the education of nurses must also evolve to
      meet these changes. Curriculum transformation is needed at nearly every aspect of
      health care. This policy statement will explore these challenges and the
      transformation in nursing education required to meet them.

PMID- 29053526
TI  - Faculty and Student Perspectives on Mentorship in a Nursing Honors Program.
AB  - Honors programs in nursing can facilitate the professional development of high
      achieving students, supporting their lifelong engagement in nursing practice,
      education, research, and health care policy issues. Strong mentoring
      relationships are commonly identified as essential to the success of nursing
      honors programs, but literature on mentoring relationships in an honors context
      is limited. The purpose of this study was to gain insight into faculty and
      student expectations for mentorship. Faculty and students shared similar
      expectations for both the mentor and mentee, highlighting key themes of
      engagement, facilitation, accountability, and collaboration as necessary for the
      success of an undergraduate nursing honors program.

PMID- 29053527
TI  - A Paradigm Shift From Brick and Mortar: Full-Time Nursing Faculty Off Campus.
AB  - The organizational structure for the Master of Science in Nursing's online
      program at Sacred Heart University offers a remarkably different innovative
      faculty model. Full-time, doctorally prepared faculty reside in several different
      states and teach online but are fully integrated and immersed in all aspects of
      the college of nursing. This untraditional model, which has proven to be
      successful over time using best practices for online education, is replicable and
      offers an innovative option for online learning.

PMID- 29053528
TI  - Collaborative Testing Using Quizzes as a Method to Improve Undergraduate Nursing
      Student Engagement and Interaction.
AB  - Alternative testing methods are gaining popularity as an innovative means of
      assessing learning and retention of knowledge. Collaborative testing, an
      alternative to traditional testing, fosters interaction and collaboration among
      students. This article describes the use of collaborative testing using quizzes
      in an accelerated second-degree baccalaureate nursing program in order to enhance
      learning and retention of course content. Feedback from students was
      overwhelmingly positive, and most believed this strategy provided a structured
      method to their studying and acquisition of course concepts, which was
      particularly beneficial within an accelerated course format.

PMID- 29053529
TI  - Use of Service-Learning to Teach Health Literacy with Online Graduate Nursing
      Students.
AB  - To meet Healthy People 2020 goals, health literacy must be included in health
      care program curricula. In a fully online graduate nursing course, an innovative
      service-learning activity asked students to collaborate in the creation of low
      literacy patient education pamphlets for practice partners at a community
      rehabilitation facility. Involvement with community stakeholders such as support
      groups and interprofessional team members enhanced interdisciplinary educational
      outcomes. Through this innovative project-based activity, students were able to
      meet the clinical education and decision support needs of rehabilitation patients
      while translating academic coursework to support actual community needs.

PMID- 29053530
TI  - Innovative Teaching for Undergraduate Nursing Students Through Mastery Modeling.
AB  - Mastery modeling was implemented to support the transfer of classroom diabetes
      content to the clinical area. Interactive teaching methodologies that exemplified
      mastery modeling included scripted classroom video and vignettes, simulation
      based learning experiences, and a worksheet relating to diabetes-specific groups
      to use in the clinical setting. When mastery modeling teaching methodologies were
      implemented, transfer of knowledge through clinical reasoning was noted at a
      higher level for the diabetes-specific groups over the standard groups.

PMID- 29053531
TI  - Nursing Student Collaborative With Meals on Wheels: Home Visits for At-Risk
      Senior Adults.
AB  - Nursing students at Washington State University Tri-Cities Campus are taking part
      in a program to provide care for homebound senior adults enrolled in home
      delivery meal services. Students perform home safety, functional, and cognitive
      assessments while learning the challenges of meeting nutritional needs of an at
      risk senior adult population. This article outlines the program and its outcomes
      after two years of collaboration. Meals on Wheels is identified as an innovative
      placement for meeting nursing program outcomes and clinical practice hours. Areas
      for future growth include interdisciplinary collaboratives and partnering with
      local hospitals to study the program's impact on hospital readmission.

PMID- 29053532
TI  - Using a Complex Patient Management Scenario to Help Bridge the Education-Practice
      Gap.
AB  - Preparing nursing students for transition to practice is challenging in light of
      the increasing complexity of today's health care environment. A clinical
      simulation was developed to engage senior-level bachelor of science in nursing
      students in the management of a critically ill patient whose deterioration
      warranted timely transfer to an intensive care unit. In this fast-paced, highly
      charged simulation, students were challenged to implement priority setting,
      delegation, communication methods, and teamwork. This article examines the gaps
      in students' understanding of complex patient situations and points to the need
      for simulations that bridge the gap between education and practice.

PMID- 29053533
TI  - Use of a Single Anatomic Donor Site for Harvesting a Full-Thickness Skin Graft
      and a Free Cartilage Graft for Nasal Defects.

PMID- 29053534
TI  - Comparison of Moderate and High Energy of a Nano-Fractional Radiofrequency
      Treatment on a Photoaging Hairless Mice Model.
AB  - BACKGROUND: Fractional radiofrequency (FRF) has been widely used in skin
      rejuvenation. To explore optimal settings, it is important to compare different
      treatment parameters. OBJECTIVE: This study was designed to compare the effect of
      moderate-energy and high-energy FRF treatment on a hairless mice model. METHODS:
      Fifteen photoaged hairless mice were assigned to 3 groups: control, moderate
      energy, and high energy. Two treatment sessions (T * 1 and T * 2) were performed
      at 1-month interval. Transepidermal water loss was measured at baseline,
      immediately, 1, 2, and 4 weeks after T * 1. Skin samples were harvested before
      each treatment, 1 and 2 months after T * 2. Neocollagenesis was evaluated by
      hematoxylin and eosin staining, Masson staining, and immunohistochemistry
      analysis. RESULTS: Transepidermal water loss of high-energy group was
      significantly higher than the moderate-energy group (p = .008) immediately after
      T * 1. Remarkable fibroblast proliferation was observed at 1 month after T * 1,
      followed by significant dermal thickening, and increase of Type I collagen and
      Type III collagen. There was no significant difference between 2 energy groups in
      fibroblast proliferation, dermal thickness, and collagen density. CONCLUSION: The
      effect of moderate-energy treatment was comparable with that of high energy in
      neocollagenesis, whereas moderate energy yielded less damage to skin barrier
      function.

PMID- 29053535
TI  - Histologic Status of Squamous Cell Carcinoma In Situ After Diagnostic Biopsy in
      Immunocompetent and Immunosuppressed Patients.
AB  - BACKGROUND: The histologic status of squamous cell carcinoma in situ (SCC-IS)
      after diagnostic biopsy has not been well described or compared between
      immunocompetent and immunosuppressed patients. Expression of immunohistochemical
      (IHC) markers of aggressive SCC has not been compared between SCC-IS that clears
      or becomes invasive after biopsy. OBJECTIVE: To determine the histologic status
      of SCC-IS after diagnostic biopsy in these populations. METHODS: Retrospective
      analysis of 129 patients with SCC-IS treated with excision and 55 patients
      treated with Mohs surgery. Histologic features of SCC in excised tissue after
      biopsy were recorded. Known SCC markers were evaluated using IHC. RESULTS:
      Invasive SCC was found in 3% to 16% of residual SCC-IS depending on surgical
      treatment modality. The history of skin cancer increased the odds of having
      invasive SCC in SCC-IS excisions (odds ratio 7.1, p < .05). Forty-seven percent
      of SCC-IS in immunosuppressed patients cleared after diagnostic biopsy compared
      with 70% in immunocompetent patients (p < .05). Inflammatory infiltrate and
      molecular markers of aggressive SCCs (Ki-67, matrix metalloproteinase [MMP]-9,
      MMP-7, transforming growth factor-beta (TGFbeta)-RI, TGFbeta-RII, and Sox-2) were
      not predictive of residual or invasive SCC at the time of treatment. CONCLUSION:
      Up to 16% of SCC-IS showed invasive SCC at the time of surgical treatment.
      Immunosuppressed patients are more likely to have residual disease after biopsy.
      IHC markers of invasive SCC may not predict invasion.

PMID- 29053536
TI  - ATX-101 (Deoxycholic Acid Injection) for Paradoxical Adipose Hyperplasia
      Secondary to Cryolipolysis.

PMID- 29053538
TI  - Commentary on Intracranial Penetration During Temporal Soft Tissue Filler
      Injection.

PMID- 29053537
TI  - Thermal Ultra Short Photodynamic Therapy: Heating Fibroblasts During Sub-30
      Minute Incubation of 5-Aminolevulinic Acid Increases Photodynamic Therapy-Induced
      Cell Death.
AB  - BACKGROUND: Actinic keratoses (AKs) prevalence was estimated at 39.5 million
      Americans in 2004, and the cost to treat AKs that year was approximately 1
      billion dollars. Photodynamic therapy (PDT) is an FDA-approved therapy for the
      treatment of AK. Recent studies have focused on reducing PDT treatment time while
      maintaining efficacy. OBJECTIVE: To investigate the use of thermal modulation to
      improve the efficacy of ultra short aminolevulinic acid (ALA) incubation PDT.
      MATERIALS AND METHODS: Human dermal fibroblasts (HDFs) were incubated for 10, 15,
      or 20 minutes with 0.5-mM ALA at various temperatures (21, 24, 27, 30, 33, 36,
      39, and 42 degrees C). After ALA incubation, samples were treated for 1,000
      seconds with blue light (417 +/- 5 nm) resulting in a fluence of 10 J/cm. Samples
      were collected and stained for apoptosis/necrosis with annexin-V and 7
      aminoactinomycin D (7-AAD), then analyzed by flow cytometry. RESULTS: Human
      dermal fibroblast treated with 10-minute ALA-PDT had no statistically significant
      changes in apoptosis at all temperatures. Human dermal fibroblast treated with 15
      or 20-minute ALA-PDT had statistically significant increases in apoptosis at 39
      and 42 degrees C (p < .05). CONCLUSION: These results suggest the use of thermal
      modulation may improve ultra short ALA incubation PDT efficacy.

PMID- 29053539
TI  - Management of Incompletely Excised Skin Tumors: Our Experience.
AB  - BACKGROUND: Current British Association of Dermatologists guidelines recommend
      that Mohs micrographic surgery should be considered for incompletely excised
      basal cell carcinomas and squamous cell carcinomas. Units that perform Mohs
      surgery are limited. In Teesside, the skin cancer multidisciplinary team
      discusses all incompletely excised skin tumors, considers all treatment options,
      provides recommendations, and initiates the agreed management plan. OBJECTIVE: To
      assess the outcome and appropriateness of local surgical macroexcision for
      incompletely excised skin tumors. METHODS: The authors performed a retrospective
      analysis of the local skin multidisciplinary team notes from July 2010 to July
      2012 identifying all incompletely excised skin cancers. A total of 46 basal cell
      carcinomas and 27 squamous cell carcinomas were incompletely excised. Case note
      and pathology report review was used to identify the recommended management
      option and subsequent outcome. RESULTS: Fifty-four of the 73 incompletely excised
      tumor identified underwent further surgical excision locally. Fifty-one of 54
      patients (94.4%) had successful completion of excision with a single procedure.
      The remaining 3 patients' required further surgery, performed locally, to
      completely excise their tumor. Average follow-up was 35 months with 1 (1.9%)
      recurrence. CONCLUSION: In the authors' region, local surgical management of
      incompletely excised skin tumors has yielded results comparable to Mohs surgery.
      Mohs surgery remains a viable option in specific cases.

PMID- 29053540
TI  - Reconstruction of Large Auricular and External Auditory Canal Defect With Novel
      Guiding Sutures Placed in a Spoke Wheel Pattern.

PMID- 29053541
TI  - Commentary on Long-Pulsed Nd: YAG Laser Treatment for Nail Psoriasis.

PMID- 29053542
TI  - Biomechanical Comparison of Intrapelvic and Extrapelvic Fixation for Acetabular
      Fractures Involving the Quadrilateral Plate.
AB  - OBJECTIVES: Elderly patients represent the fastest growing and most difficult to
      treat population sustaining acetabular fractures. When treated surgically,
      isolated extrapelvic or combined intrapelvic-extrapelvic constructs may be used.
      No biomechanical or clinical study has compared the merits of these 2 techniques
      in cadaveric models. This research aims to biomechanically quantify the
      additional benefit of intrapelvic fixation to a standard extrapelvic fixation
      construct. METHODS: Ten cadaveric pelves underwent standardized anterior column
      and quadrilateral plate fracture creation. One hemipelvis from each subject
      received isolated extrapelvic fixation, whereas the other received adjunctive
      intrapelvic fixation. Specimens were then subjected to a 50% of body weight (BW)
      nondestructive stiffness test followed by loading to failure. For the 50% BW
      test, displacement at 50% BW and stiffness were calculated. For the load to
      failure test, stiffness, elastic energy, and plastic energy were calculated.
      Yield point, force at clinical failure (defined at 2 mm of displacement), and
      maximum force were also identified. A Wilcoxon matched-pairs t test was used to
      compare fixation groups. RESULTS: The addition of an intrapelvic plate improved
      construct performance for all test parameters. A statistically significant
      difference (P < 0.05) was reached for yield force, maximum force, and plastic
      energy. CONCLUSIONS: These findings demonstrate that the addition of intrapelvic
      plating may offer distinct advantages in prevention of catastrophic construct
      failure in situations in which significant lateral to medial force is applied to
      the greater trochanter such as patient falling.

PMID- 29053543
TI  - Decreased Time to Antibiotic Prophylaxis for Open Fractures at a Level One Trauma
      Center.
AB  - OBJECTIVE: To determine whether time to administration of antibiotics decreased
      after the implementation of an open fracture working group and antibiotic
      prophylaxis protocol. DESIGN: Retrospective cohort study. SETTING: One Level 1
      Trauma Center. PATIENTS: Patients 18 years of age and older who sustained an open
      fracture and presented directly to our emergency department. INTERVENTION: Prompt
      irrigation and debridement in the operating room and fracture stabilization
      dictated by the treating surgeon. Fifty patients were reviewed as the
      preintervention group, comprising the period before conception and before
      intervention. Fifty patients were included after the initiation of our protocol
      during the same time period 1 year later. MAIN OUTCOME MEASUREMENTS: Time from
      entrance to the emergency department to ordering of antibiotics, time from
      ordering to administration of antibiotics, and time from entrance to the
      emergency department to administration of antibiotics. RESULTS: After protocol
      implementation, time from admission to antibiotic administration decreased
      significantly from 123.1 to 35.7 minutes (P = 0.0003). Each component decreased
      significantly: admission to order decreased from 94.1 to 26.1 minutes, and order
      to administration decreased from 29.0 to 9.5 minutes (P = 0.0046 and P = 0.0003).
      CONCLUSION: Our study demonstrates a significantly reduced time to antibiotic
      prophylaxis for patients with open fractures after the implementation of a
      multidisciplinary working group. We hope that this provides a model for
      institutions to improve care and outcomes of these injuries. LEVEL OF EVIDENCE:
      Therapeutic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29053544
TI  - The Correlation Between the OTA/AO Classification System and Compartment Syndrome
      in Both Bone Forearm Fractures.
AB  - OBJECTIVE: To evaluate the efficacy of using the Orthopaedic Trauma Association
      (OTA/AO) classification for both bone forearm fractures in predicting compartment
      syndrome. DESIGN: Retrospective cohort. SETTING: Level 1 Academic Trauma Center.
      PATIENTS/PARTICIPANTS: One hundred fifty-one patients 18 years of age and older,
      with both bone forearm fractures diagnosed from 2001 to 2016 were categorized
      based on the OTA/AO classification. Patients with both bone fractures caused by
      gunshot wounds were excluded. MAIN OUTCOME MEASUREMENTS: The endpoint for our
      study was whether forearm fasciotomies were performed based on the presence of
      compartment syndrome. RESULTS: Of a total of 151 both bone forearm fractures, 15%
      underwent fasciotomy. Six of 80 (7.5%) grouped 22-A3, 8 of 44 (18%) grouped 22
      B3, and 9 of 27 (33%) grouped 22-C underwent fasciotomies for compartment
      syndrome (P = 0.004). The relative risks of developing compartment syndrome for
      group 22-B3 versus 22-A3 was 2.42 (P = 0.08), 22-C versus 22-B3 was 1.83 (P =
      0.15), and 22-C versus 22-A3 was 4.44 (P = 0.002). CONCLUSIONS: There is a
      significant correlation between the OTA/AO classification and the need for
      fasciotomies, with group C fractures representing the highest risk. Clinicians
      can use this information to have a higher index of suspicion for compartment
      syndrome based on OTA/AO classification to help minimize the risk of a missed
      diagnosis. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29053545
TI  - Three-Dimensional Deformities of Nonoperative Midshaft Clavicle Fractures: A
      Surface Matching Analysis.
AB  - OBJECTIVE: The purpose of this study was to describe the 3-dimensional
      deformities of midshaft clavicle fractures, which had been treated
      nonoperatively, using computed tomography (CT) surface matching. METHODS: Twenty
      one patients with unilateral midshaft clavicle fracture, who had been treated
      nonoperatively, were enrolled and evaluated retrospectively. The 3-dimensional
      deformity of the fractured clavicle was evaluated by CT surface matching. CT
      scans of 21 age- and sex-matched patients with initial traumatic shoulder
      dislocation or proximal humeral fracture were enrolled as a control group, and
      the differences in 3-dimensional deformities and lengths of the clavicles between
      the fracture group and the control group were evaluated. A correlation analysis
      was also performed between rotational deformities and clavicular length
      shortening. RESULTS: The affected clavicle showed 1.3 +/- 6.9 degrees of downward
      angular deformity, 2.1 +/- 8.0 degrees of anterior angular deformity, and 5.0 +/-
      4.9 degrees of anterior rotational deformity. Compared with the control group,
      the fractured clavicle showed larger anterior rotational deformity (P = 0.021).
      Shortening of the clavicle demonstrated negative correlation with anterior axial
      rotation (R = -0.534, P = 0.013), but no correlation was found between clavicular
      shortening and the other 2 rotational deformities. CONCLUSION: In cases of
      midshaft clavicle fracture, the distal fragment usually rotates anteriorly
      because of its anatomical relationships. Shortening deformity after clavicle
      fracture was reported to change shoulder kinematics, and anterior rotational
      deformity might adversely affect scapular motion.

PMID- 29053546
TI  - Histopathology of Calciphylaxis: Cohort Study With Clinical Correlations.
AB  - Calciphylaxis is a rare, painful, and life-threatening condition with a high
      mortality rate. Although the etiology of calciphylaxis is not well understood, it
      has been proposed that calcium deposition within and around subcutaneous vessels
      restricts blood flow chronically, thereby predisposing the patient to acute
      pannicular and dermal thrombosis. Given increasing recognition of the role of
      hypercoagulability in calciphylaxis, this retrospective cohort study sought to
      evaluate the presence of thromboses and dermal angioplasia in calciphylaxis.
      Moreover, we aimed to validate previous observations about the histopathology of
      calciphylaxis compared with skin biopsies from patients with end-stage renal
      disease but without calciphylaxis. After a meticulous clinical chart review, we
      assessed the corresponding skin biopsies for the presence of vessel
      calcification, thromboses, and dermal angioplasia in skin biopsies from patients
      with calciphylaxis (n = 57) and compared with those from patients with end-stage
      renal disease but without calciphylaxis (n = 26). Histopathologic findings were
      correlated with clinical features such as chronic kidney disease, diabetes, or
      associated malignancy. Our results validated a prior observation that
      calciphylaxis was significantly more likely to show calcification of dermal
      vessels and diffuse dermal thrombi. This study reports the frequent finding of
      dermal angioplasia, a potential marker of chronic low-grade ischemia, as another
      frequent microscopic finding in calciphylaxis. Among cases of calciphylaxis,
      histopathologic changes in patients with chronic kidney disease were
      indistinguishable from those in patients without chronic kidney disease, thereby
      implying a final common pathogenic pathway in both uremic and nonuremic
      calciphylaxis. In future, larger, prospective studies may be useful in validating
      these findings.

PMID- 29053547
TI  - Primary Cutaneous Sarcomatoid Anaplastic Lymphoma Kinase-Positive Anaplastic
      Large-Cell Lymphoma With Linear Distributional Lesions.
AB  - We report a case of cutaneous anaplastic lymphoma kinase-positive anaplastic
      large-cell lymphoma (ALCL) with linear distributional lesions and sarcomatoid
      histologic features. A sarcomatoid variant is the rarest morphological pattern of
      ALCL. Interestingly, the morphology of tumor cells in the present case
      transitioned from a sarcomatoid variant of ALCL at first diagnosis to a classic
      variant at relapse. The case is a diagnostic challenge considering both the
      clinical and histologic aspects. Awareness of the sarcomatoid variant of ALCL and
      its morphological changes can lead to a correct diagnosis.

PMID- 29053548
TI  - Asymptomatic Soft Erythematous Dome-Shaped Papule on the Chest: Answer.

PMID- 29053549
TI  - Tense Bullae on the Penile Shaft: Answer.

PMID- 29053550
TI  - White Goose Bumps All Over the Body: Answer.

PMID- 29053551
TI  - Asymptomatic Soft Erythematous Dome Shaped Papule on the Chest: Challenge.

PMID- 29053552
TI  - Tense Bullae on the Penile Shaft: Challenge.

PMID- 29053553
TI  - White Goose Bumps All Over the Body: Challenge.

PMID- 29053554
TI  - The Sustainable Development Goals and Health Equity.

PMID- 29053555
TI  - Case Series Analysis of Myopic Progression Control With a Unique Extended Depth
      of Focus Multifocal Contact Lens.
AB  - OBJECTIVES: To determine the rate of myopia progression in children fit with a
      commercially available extended depth of focus (center distance) multifocal soft
      contact lens with attributes theoretically expected to slow the progression of
      myopia. METHODS: A retrospective case series analysis of 32 patients (ages 6-19
      years, mean 10.98+/-2.95) from 10 practice locations was performed. At initial
      presentation, 44% wore spectacles, 37.5% spherical soft contact lenses, 15.6% a
      different soft multifocal contact lens, and 3% orthokeratology lenses. All
      participants showed progression of at least -0.50 diopter with current
      corrections and were fit with an extended depth of focus (center distance)
      multifocal soft contact lens (NaturalVue Multifocal 1 Day Contact Lenses;
      Visioneering Technologies, Inc., Alpharetta, GA). Follow-up time was 6 to 25
      months (mean: 10.94+/-4.76). RESULTS: Reductions in the annualized rate of myopic
      progression from -0.85 D per year +/-0.43 D to -0.04 D per year +/-0.18 D
      (P<0.00000) OD, -0.90 D per year +/-0.57 D to -0.03 D per year +/-0.17 D
      (P<0.00000) OS were observed. These data represent a reduction of 95.4% OD and
      96.25% OS. Approximately 98.4% of the children showed reduction of annualized
      myopic progression; 91% showed a decrease of 70% or greater. Overall, 81.25%
      showed complete halting of myopic progression, including 6.25% demonstrating
      myopic regression. CONCLUSIONS: This unique extended depth of focus (center
      distance) daily disposable multifocal contact lens was effective in slowing
      myopic progression in these children. These findings add to the growing evidence
      that center distance multifocal soft contact lenses may slow the progression of
      myopia.

PMID- 29053556
TI  - Epithelial Erosions and Refractive Results After Single-Step Transepithelial
      Photorefractive Keratectomy and Alcohol-Assisted Photorefractive Keratectomy in
      Myopic Eyes: A Comparative Evaluation Over 12 Months.
AB  - PURPOSE: To evaluate the epithelial erosion incidence and refractive results in
      myopic eyes undergoing single-step transepithelial photorefractive keratectomy
      (TransPRK) compared with alcohol-assisted photorefractive keratectomy (PRK).
      METHODS: This was a retrospective nonrandomized comparative study conducted at
      the American University of Beirut Medical Center. A total of 189 eyes that had
      undergone single-step transepithelial PRK (TransPRK) were compared with 189
      matched eyes that had undergone alcohol-assisted PRK over a follow-up of 1 year.
      The incidence and symptoms of epithelial erosion were evaluated in both treatment
      groups using a post hoc questionnaire administered to patients selected in the
      study. Visual and refractive outcomes, including vector analysis of astigmatism,
      and corneal higher-order aberrations were also compared at 1-year
      postoperatively. RESULTS: Baseline characteristics were similar between 2 groups
      (P > 0.05). A slight difference was detected at 12-month follow-up in the
      refractive cylinder (P = 0.02) and difference vector (P = 0.01) between eyes that
      had undergone TransPRK versus alcohol-assisted PRK. All other visual and
      refractive outcomes were similar at 12-month follow-up between both groups. Of
      note, 9.9% of patients with alcohol-assisted PRK (10/101) reported to the clinic
      because of tearing and stabbing sensation within 1 week after contact lens
      removal as opposed to 1% (1/100) of the TransPRK group (P = 0.0097). Subclinical
      recurrent epithelial erosion symptoms occurred more frequently in alcohol
      assisted PRK: soreness to touch, sharp pains, and eyelid sticking occurred in
      26.0% versus 6.6%, 32.5% versus 7.9%, and 26.0% versus 6.6% among the patients
      who were treated with alcohol-assisted PRK versus those who were treated with
      TransPRK, respectively (P <= 0.002). CONCLUSIONS: Single-step TransPRK for myopic
      eyes yields refractive results similar to those of alcohol-assisted PRK but shows
      a lesser incidence of early postoperative epithelial erosions and subsequent
      subclinical recurrent erosions.

PMID- 29053557
TI  - Bacterial Keratitis: Isolated Organisms and Antibiotic Resistance Patterns in San
      Francisco.
AB  - PURPOSE: Understanding the spectrum of pathogens in a given geographic region is
      important when deciding on empiric antibiotic therapy. In this study, we evaluate
      the spectrum of bacterial organisms cultured from corneal samples and their
      antibiotic sensitivities to guide initial treatment of keratitis. METHODS: We
      performed a retrospective case review of cultures from suspected infectious
      keratitis cases at the Francis I. Proctor Foundation, University of California,
      San Francisco, from 1996 through 2015. Logistic regression models were used to
      assess the risk of culturing methicillin-resistant Staphylococcus aureus (MRSA)
      from ulcers over time and the association between the year cultured and
      moxifloxacin resistance. RESULTS: A total of 522 of 2203 (23.7%) cultures grew
      bacterial organisms believed to be the etiology of infection, with available
      antibiotic sensitivity data. Of these, 338 (65.3%) grew gram-positive organisms
      with the most common being methicillin-sensitive Staphylococcus aureus (20.1%, N
      = 105). One hundred eighty (34.7%) grew gram-negative species with Pseudomonas
      aeruginosa as the most prevalent organism (10.9%, N = 57). There was 1.13
      increased odds of culturing MRSA for each 1-year increase in the culture date (P
      = 0.01) and 1.26 increased odds of culturing an organism resistant to
      moxifloxacin with each 1-year increase in the culture date after controlling for
      the infectious organism (P < 0.001). CONCLUSIONS: Gram-positive organisms are the
      most commonly identified etiology of microbial keratitis in this series.
      Approximately 35% of cultured organisms had variable susceptibility to
      moxifloxacin, and resistance seems to be increasing over time. The risk of
      culturing MRSA increased over time.

PMID- 29053558
TI  - In Vivo Confocal Microscopy Reveals Corneal Reinnervation After Treatment of
      Neurotrophic Keratopathy With Corneal Neurotization.
AB  - PURPOSE: To document the presence and location of new sensory nerve fibers after
      corneal neurotization using in vivo confocal microscopy (IVCM) in 2 patients with
      neurotrophic keratopathy (NK). METHODS: Two patients with unilateral advanced NK
      received corneal neurotization to surgically reinnervate the cornea. IVCM was
      used to identify subbasal nerve fibers and document corneal reinnervation. In 1
      patient (case 1), IVCM was performed before and after corneal neurotization; in
      the second patient (case 2), IVCM was performed after neurotization and corneal
      transplantation. RESULTS: In case 1, who had hand motion visual acuity due to NK
      associated corneal perforation that necessitated cyanoacrylate gluing,
      preoperative IVCM identified no subbasal nerves; however, subbasal nerves were
      identified 6 months after corneal neurotization, and there were no further
      episodes of persistent epithelial defects. In case 2, in whom NK with a total
      absence of corneal sensation was the result of treated basal skull meningioma,
      corneal sensation, visual acuity, and ocular surface health improved after
      corneal neurotization. Deep anterior lamellar keratoplasty was performed 2.5
      years after corneal sensation was reestablished. IVCM demonstrated corneal
      reinnervation at the stromal and subbasal level in a pattern different from the
      normal cornea. CONCLUSIONS: Corneal neurotization restores corneal sensation by
      reinnervating the stromal and subbasal layers of the cornea. In doing so, corneal
      neurotization may halt the process of NK and prevent further visual loss.

PMID- 29053559
TI  - Functional Role of Lacrimal Gland Fibroblasts in a Mouse Model of Chronic Graft
      Versus-Host Disease.
AB  - PURPOSE: This study aimed to clarify the mechanisms and assess the
      characteristics of the chronic graft-versus-host disease (cGVHD) fibrosis in the
      lacrimal gland (LG) of mice. METHODS: Histopathology of LG tissues was examined
      by immunohistochemistry and electron microscopy. Cultured fibroblasts derived
      from the LG were analyzed by phase-contrast microscopy, immunocytochemistry, flow
      cytometry, proliferation assay, and invasion and migration assays. RESULTS:
      Cultured murine LG fibroblasts in cGVHD were spindle-shaped and relatively small,
      whereas those from syngeneic controls were polygon-shaped and relatively large.
      Flow cytometric analysis showed that the LG fibroblasts in cGVHD had elevated
      HSP47 levels. The LG fibroblasts in cGVHD also showed increased expression of
      major histocompatibility complex class II. Furthermore, the proportion of Sca
      1PDGFR-alpha cells among the LG fibroblasts in cGVHD was considerably increased
      compared with controls. Cell counting kit-8 assays demonstrated that the LG
      fibroblasts in cGVHD were highly proliferative, and cell invasion assays
      indicated that they were highly invasive with high migration ability.
      CONCLUSIONS: LG fibroblasts in cGVHD can be aberrantly activated, thereby
      eliciting fibrosis by producing excessive extracellular matrix, leading to LG
      dysfunction in mice.

PMID- 29053560
TI  - Evaluation of Human Corneal Lenticule Quality After SMILE With Different Cap
      Thicknesses Using Scanning Electron Microscopy.
AB  - PURPOSE: To evaluate the surface characteristics of lenticules created by small
      incision lenticule extraction (SMILE) with different cap thicknesses. METHODS:
      This prospective study included 20 consecutive patients who underwent bilateral
      SMILE. Surface regularity of the extracted corneal lenticule was analyzed using
      scanning electron microscopy (SEM) combined with 2 methods: qualitative and
      quantitative regularity. Qualitative regularity of SEM images was graded by
      masked observers using an established scoring system. Quantitative regularity of
      SEM images was assessed by counting the total number and areas of tissue bridges
      using Image-Pro Plus software. Four different cap thickness of 120, 130, 140, and
      150 MUm were compared. Refractive outcomes of patients were measured at baseline
      and 1 month after surgery. RESULTS: As 10 specimens were not analyzable, only 30
      eyes were included. Postoperatively, all eyes had postoperative uncorrected
      distance visual acuity of 20/20 or better; 43% had an unchanged corrected
      distance visual acuity; 43% gained 1 line; 10% lost 1 line. Ultrastructurally,
      surface irregularity was primarily caused by tissue bridges. The average surface
      regularity score obtained was 10.87 +/- 2.40 for 120 MUm, 10.78 +/- 2.60 for 130
      MUm, 8.76 +/- 2.16 for 140 MUm, and 8.70 +/- 2.66 for 150 MUm (P < 0.001). The
      total number and areas of tissue bridges of 120 to 130 MUm were significantly
      less than 140 to 150 MUm (P < 0.05). Surface regularity decreased as cap
      thickness increased (P < 0.05). CONCLUSIONS: There is smoother appearance of the
      lenticular surface as seen through SEM when a thin cap is created compared with a
      thick cap qualitatively and quantitatively.

PMID- 29053561
TI  - Recognizing and Managing Bullous Descemet Detachment Secondary to Accidental
      Hydroseparation During Phacoemulsification/Cataract Surgery by Relaxing
      Descemetotomy.
AB  - PURPOSE: To report a new technique called relaxing Descemetotomy for treatment of
      bullous Descemet detachment (BDD) secondary to accidental hydroseparation of
      Descemet membrane (DM) during stromal hydration in cataract surgery. METHODS: A
      clear corneal keratome entry was created close to the limbus extending inward to
      create a relaxing cut (ab externo relaxing Descemetotomy) on taut DM, thus
      creating an egress route for supra-Descemetic fluid (SDF). This was followed by
      pneumodescemetopexy to drain SDF internally. RESULTS: Three patients with a
      history of unsuccessful pneumodescemetopexy and with planar or mildly convex
      separation of DM without break on anterior segment optical coherence tomography
      (ASOCT) underwent this procedure. All had successful reapposition of DM
      clinically and on ASOCT. All showed resolution of stromal edema and improved
      uncorrected and best-corrected visual acuity postoperatively. CONCLUSIONS: Rarely
      stromal hydration performed with an irrigating cannula positioned too close to
      the posterior stroma can result in hydroseparation of DM creating BDD, seen
      intraoperatively as a fluid wave propagating across the posterior aspect of the
      cornea. Large folds, free mobility, and DM tear classically seen with
      rhegmatogenous Descemet detachment are not seen clinically or on ASOCT in BDD.
      Pneumodescemetopexy alone cannot resolve BDD because without a DM tear, SDF
      cannot evacuate. Combining relaxing Descemetotomy with pneumodescemetopexy allows
      SDF to drain internally and Descemet detachment to resolve. This technique has
      numerous advantages over classical venting incisions in terms of ease, preferable
      limbal location, larger incision size, absence of complications such as visual
      axis scars, irregular astigmatism, epithelial ingrowth, infectious keratitis,
      etc.

PMID- 29053562
TI  - Predictive Factors for Corneal Clearance After Descemetorhexis Without
      Endothelial Keratoplasty.
AB  - PURPOSE: To study preoperative factors that possibly contribute to corneal
      clearance after Descemetorhexis without endothelial keratoplasty (DWEK) and to
      determine the most successful surgical technique for the procedure. METHODS:
      Retrospective chart review of 17 eyes of 13 patients with Fuchs corneal
      endothelial dystrophy that underwent central 4-mm DWEK. RESULTS: Baseline age,
      pachymetry, and endothelial cell count were not statistically significantly
      different between eyes that cleared 0 to 2 months, 3 to 5 months, 6 to 8 months,
      or that failed to clear. All eyes that failed to clear had DWEK performed using
      scoring followed by the stripping technique. Postoperative endothelial cell
      counts steadily increased over time after the procedure, even in eyes that failed
      to clear. CONCLUSIONS: DWEK when performed with a Descemetorhexis technique
      results in corneal clearance in the majority of cases regardless of baseline
      demographics, with clearance typically 3 months after the procedure. Further
      studies are needed to investigate environmental factors, such as possible growth
      factors in the anterior chamber, that may influence clearing in these cases.

PMID- 29053563
TI  - New Pterygium Surgical Techniques Require Standardization of Outcome Measures.

PMID- 29053564
TI  - Gout Keratitis: A Case of Peripheral Ulcerative Keratitis Secondary to Gout With
      a Review of the Literature.
AB  - PURPOSE: To report a case of peripheral ulcerative keratitis secondary to gout.
      METHODS: A 41-year-old man with a history of severe gout disease presented with
      pain and redness of the right eye. Physical examination revealed 2 areas of
      peripheral corneal thinning with overlying epithelial defects. Adjacent to these
      areas, reflective crystals were identified in the corneal stroma. Anterior
      segment optical coherence tomography demonstrated stromal corneal deposits.
      RESULTS: Systemic workup was negative aside from an elevated serum uric acid
      level. The patient was administered oral prednisone, allopurinol, and colchicine.
      At his 2-month follow-up visit, the patient was asymptomatic and his corneal
      thinning had significantly improved. CONCLUSIONS: Gout is the most common type of
      inflammatory arthritis in adults with rising incidence and prevalence. Ocular
      findings in gout are common, but patients are usually asymptomatic. Monosodium
      urate crystal deposition has been reported to occur in various parts of the eye,
      with and without ocular inflammation. Crystal deposition in the cornea is
      extremely rare and may be a cause of peripheral ulcerative keratitis.

PMID- 29053565
TI  - A Synthetic Analogue of Neopeltolide, 8,9-Dehydroneopeltolide, Is a Potent Anti
      Austerity Agent against Starved Tumor Cells.
AB  - Neopeltolide, an antiproliferative marine macrolide, is known to specifically
      inhibit complex III of the mitochondrial electron transport chain (mETC).
      However, details of the biological mode-of-action(s) remain largely unknown. This
      work demonstrates potent cytotoxic activity of synthetic neopeltolide analogue,
      8,9-dehydroneopeltolide (8,9-DNP), against starved human pancreatic
      adenocarcinoma PANC-1 cells and human non-small cell lung adenocarcinoma A549
      cells. 8,9-DNP induced rapid dissipation of the mitochondrial membrane potential
      and depletion of intracellular ATP level in nutrient-deprived medium. Meanwhile,
      in spite of mTOR inhibition under starvation conditions, impairment of
      cytoprotective autophagy was observed as the lipidation of LC3-I to form LC3-II
      and the degradation of p62 were suppressed. Consequently, cells were severely
      deprived of energy sources and underwent necrotic cell death. The autophagic flux
      inhibited by 8,9-DNP could be restored by glucose, and this eventually rescued
      cells from necrotic death. Thus, 8,9-DNP is a potent anti-austerity agent that
      impairs mitochondrial ATP synthesis and cytoprotective autophagy in starved tumor
      cells.

PMID- 29053566
TI  - Different Levels of Skin Whitening Activity among 3,6-Anhydro-l-galactose,
      Agarooligosaccharides, and Neoagarooligosaccharides.
AB  - 3,6-Anhydro-l-galactose (AHG), a major monomeric constituent of red macroalgae
      (Rhodophyta), was recently reported to possess skin whitening activity. Moreover,
      AHG-containing oligosaccharides, such as agarooligosaccharides (AOSs) and
      neoagarooligosaccharides (NAOSs), have various physiological activities,
      including anti-inflammatory, antioxidant, and skin moisturizing effects. In this
      study, AHG and NAOSs were produced from agarose by enzymatic reactions catalyzed
      by an endo-type beta-agarase, an exo-type beta-agarase, and a neoagarobiose
      hydrolase. In a cell proliferation assay, AHG, AOSs, and NAOSs at 12.5, 25, and
      50 MUg/mL concentrations did not exhibit cytotoxicity toward murine B16 melanoma
      cells or human epidermal melanocytes. In an in vitro skin whitening activity
      assay of AHG, AOSs, and NAOSs at 50 MUg/mL, AHG showed the highest skin whitening
      activity in both murine B16 melanoma cells and human epidermal melanocytes; this
      activity was mediated by the inhibition of melanogenesis. Neoagarotetraose and
      neoagarohexaose also exhibited in vitro skin whitening activity, whereas
      neoagarobiose and AOSs with degrees of polymerization of 3 (agarotriose), 5
      (agaropentaose), and 7 (agaroheptaose) did not. Therefore, AHG is responsible for
      the skin whitening activity of agar-derived sugars, and the structural
      differences among the AHG-containing oligosaccharides may be responsible for
      their different skin whitening activities.

PMID- 29053567
TI  - Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest
      and Apoptosis in the MCF-7 Cancer Cell Line.
AB  - Green products have strong potential in the discovery and development of unique
      drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful
      cytotoxicity against cells that cause breast cancer. The present study aims to
      examine the cell cycle profile, status of cell death, and pathways of apoptosis
      in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti
      proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle
      analysis and the mode of cell death were evaluated using a flow cytometry
      instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the
      expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells
      in a dose-dependent manner. The 50% growth inhibition concentration (IC50) of ZnO
      NPs at 24 h was 121 ug/mL. Cell cycle analysis revealed that ZnO NPs induced sub
      G1 phase (apoptosis), with values of 1.87% at 0 MUg/mL (control), 71.49% at IC25,
      98.91% at IC50, and 99.44% at IC75. Annexin V/propidium iodide (PI) flow
      cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The
      pro-apoptotic genes p53, p21, Bax, and JNK were upregulated, whereas anti
      apoptotic genes Bcl-2, AKT1, and ERK1/2 were downregulated in a dose-dependent
      manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through
      several signalling pathways.

PMID- 29053568
TI  - Mutation of a Conserved Nuclear Export Sequence in Chikungunya Virus Capsid
      Protein Disrupts Host Cell Nuclear Import.
AB  - Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent
      outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of
      the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV
      RNA genome, is able to translocate to the host cell nucleus. In encephalitic
      alphaviruses nuclear translocation induces host cell shut off; however, the role
      of capsid protein nuclear localisation in arthritogenic alphaviruses remains
      unclear. Using replicon systems, we investigated a nuclear export sequence (NES)
      in the N-terminal region of capsid protein; analogous to that found in
      encephalitic alphavirus capsid but uncharacterised in CHIKV. The chromosomal
      maintenance 1 (CRM1) export adaptor protein mediated CHIKV capsid protein export
      from the nucleus and a region within the N-terminal part of CHIKV capsid protein
      was required for active nuclear targeting. In contrast to encephalitic
      alphaviruses, CHIKV capsid protein did not inhibit host nuclear import; however,
      mutating the NES of capsid protein (?NES) blocked host protein access to the
      nucleus. Interactions between capsid protein and the nucleus warrant further
      investigation.

PMID- 29053569
TI  - Optimal Deployment of Sensor Nodes Based on Performance Surface of Underwater
      Acoustic Communication.
AB  - The underwater acoustic sensor network (UWASN) is a system that exchanges data
      between numerous sensor nodes deployed in the sea. The UWASN uses an underwater
      acoustic communication technique to exchange data. Therefore, it is important to
      design a robust system that will function even in severely fluctuating underwater
      communication conditions, along with variations in the ocean environment. In this
      paper, a new algorithm to find the optimal deployment positions of underwater
      sensor nodes is proposed. The algorithm uses the communication performance
      surface, which is a map showing the underwater acoustic communication performance
      of a targeted area. A virtual force-particle swarm optimization algorithm is then
      used as an optimization technique to find the optimal deployment positions of the
      sensor nodes, using the performance surface information to estimate the
      communication radii of the sensor nodes in each generation. The algorithm is
      evaluated by comparing simulation results between two different seasons (summer
      and winter) for an area located off the eastern coast of Korea as the selected
      targeted area.

PMID- 29053570
TI  - Magnetic Field Sensing Based on Bi-Tapered Optical Fibers Using Spectral Phase
      Analysis.
AB  - A compact, magnetic field sensor system based on a short, bi-tapered optical
      fiber (BTOF) span lying on a magnetic tape was designed, fabricated, and
      characterized. We monitored the transmission spectrum from a broadband light
      source, which displayed a strong interference signal. After data collection, we
      applied a phase analysis of the interference optical spectrum. We here report the
      results on two fabricated, BTOFs with different interference spectrum
      characteristics; we analyzed the signal based on the interference between a high
      order modal component and the core fiber mode. The sensor exhibited a linear
      response for magnetic field increments, and we achieved a phase sensitivity of
      around 0.28 rad/mT. The sensing setup presented remote sensing operation and low
      cost transducer magnetic material.

PMID- 29053571
TI  - Chromosome Synapsis and Recombination in Male Hybrids between Two Chromosome
      Races of the Common Shrew (Sorex araneus L., Soricidae, Eulipotyphla).
AB  - Hybrid zones between chromosome races of the common shrew (Sorex araneus) provide
      exceptional models to study the potential role of chromosome rearrangements in
      the initial steps of speciation. The Novosibirsk and Tomsk races differ by a
      series of Robertsonian fusions with monobrachial homology. They form a narrow
      hybrid zone and generate hybrids with both simple (chain of three chromosomes)
      and complex (chain of eight or nine) synaptic configurations. Using
      immunolocalisation of the meiotic proteins, we examined chromosome pairing and
      recombination in males from the hybrid zone. Homozygotes and simple heterozygotes
      for Robertsonian fusions showed a low frequency of synaptic aberrations (<10%).
      The carriers of complex synaptic configurations showed multiple pairing
      abnormalities, which might lead to reduced fertility. The recombination frequency
      in the proximal regions of most chromosomes of all karyotypes was much lower than
      in the other regions. The strong suppression of recombination in the
      pericentromeric regions and co-segregation of race specific chromosomes involved
      in the long chains would be expected to lead to linkage disequilibrium between
      genes located there. Genic differentiation, together with the high frequency of
      pairing aberrations in male carriers of the long chains, might contribute to
      maintenance of the narrow hybrid zone.

PMID- 29053572
TI  - Monitoring Bridge Dynamic Responses Using Fiber Bragg Grating Tiltmeters.
AB  - In bridge health monitoring, tiltmeters have been used for measuring rotation and
      curvature; however, their application in dynamic parameter identification has
      been lacking. This study installed fiber Bragg grating (FBG) tiltmeters on the
      bearings of a bridge and monitored the dynamic rotational angle. The dynamic
      features, including natural frequencies and mode shapes, have been identified
      successfully. The innovation presented in this paper is the first-time use of FBG
      tiltmeter readings to identify the natural frequencies of a long-span steel
      girder bridge. The identified results have been verified using a bridge finite
      element model. This paper introduces a new method for the dynamic monitoring of a
      bridge using FBG tiltmeters. Limitations and future research directions are also
      discussed in the conclusion.

PMID- 29053573
TI  - Preparation and Characterization of Ternary Antimicrobial Films of beta
      Cyclodextrin/Allyl Isothiocyanate/Polylactic Acid for the Enhancement of Long
      Term Controlled Release.
AB  - Allyl isothiocyanate (AITC) are natural essential oil components that have
      outstanding antimicrobial activities. However, low water solubility, high
      volatility, and easy degradation by heat, restricting their application in food
      packing industry. Development of the inclusion complex of beta-cyclodextrin/AITC
      (beta-CD/AITC) is a promising solution. Furthermore, the incorporation of beta
      CD/AITC complex into polylactic acid (PLA) films would be an attractive method to
      develop food antimicrobial materials. The aim of this study was to evaluate the
      enhancement in physicochemical properties, antimicrobial activities, and
      controlled release of beta-CD/AITC from such films. The addition of beta-CD/AITC
      significantly increased the flexibility and thermal stability of films. The
      Fourier transform infrared (FTIR) results revealed that the interactions between
      beta-CD/AITC and PLA films occurred. The controlled release of AITC encapsulated
      in beta-CD was significantly affected by relative humidity and temperature. The
      PLA films containing beta-CD/AITC can be applied as an effective antimicrobial
      packing material for food and non-food applications.

PMID- 29053574
TI  - Symptoms during Adolescents' First Use of Cigarettes and E-Cigarettes: A Pilot
      Study.
AB  - Symptoms adolescents experience during their first time using a cigarette predict
      their current use, but little is known regarding the symptoms experienced during
      first e-cigarette use. We conducted a pilot study to understand the symptoms
      adolescents experience when they first tried cigarettes and e-cigarettes and the
      associations between these symptoms and current use. Participants were 41
      adolescents in two U.S. cities who had tried cigarettes or e-cigarettes. We asked
      adolescents to recall the symptoms they experienced during their first cigarette
      or e-cigarette and categorized symptoms as negative (felt bad, coughing/chest
      pain, bad taste, upset stomach, dizzy/lightheaded) or positive (felt relaxed,
      rush/buzz). Adolescents reported fewer negative symptoms for first e-cigarette
      than first cigarette use (all p < 0.05). Current cigarette smoking was associated
      with endorsing fewer negative symptoms (OR = 0.49, 95% CI = [0.25, 0.95]) and
      more positive symptoms (OR = 7.11, 95% CI = [1.47, 34.33]) at first cigarette
      use. First e-cigarette use symptoms were not associated with current e-cigarette
      use. Adolescents reported fewer negative symptoms from first e-cigarette than
      from first cigarette, and e-cigarette symptoms did not influence use as they do
      for cigarettes. Additional research is needed to confirm these findings in
      longitudinal studies.

PMID- 29053575
TI  - The Impact of a Weight Loss Intervention on Diet Quality and Eating Behaviours in
      People with Obesity and COPD.
AB  - There is a paucity of evidence to guide clinicians about appropriate management
      strategies for people with obesity and Chronic Obstructive Pulmonary Disease
      (COPD). We have recently published results from the first weight loss
      intervention in adults (>18 years) with obesity (body mass index; BMI >= 30
      kg/m2) and COPD, using a low-calorie diet coupled with a partial meal replacement
      plan and resistance exercise training, which resulted in a 6.4% reduction in
      weight while maintaining skeletal muscle mass and improving health status. This
      sub-study aims to evaluate the intervention by (a) examining changes in dietary
      intake and nutritional biomarkers and (b) examining predictors of weight loss.
      Dietary intake was evaluated using four-day food diaries, and analysis of plasma
      fatty acids and plasma carotenoids as biomarkers of dietary fat intake and fruit
      and vegetable intake, respectively. Twenty-eight obese COPD subjects (n = 17
      males, n = 11 females) with a mean (standard deviation; SD) age of 67.6 (6.3)
      years completed the 12-week weight loss intervention. Pre-intervention, mean (SD)
      BMI was 36.3 (4.6) kg/m2. Micronutrient intake improved from pre- to post
      intervention, with the percentage of subjects meeting the Nutrient Reference
      Values increased for all micronutrients. Post-intervention, significant decreases
      in total (p = 0.009) and saturated fat intake (p = 0.037), and corresponding
      decreases in total (p = 0.007) and saturated plasma fatty acids (p = 0.003) were
      observed. There was a trend towards higher total carotenoids post-intervention (p
      = 0.078). Older age (p = 0.025), higher pre-intervention uncontrolled eating (p <
      0.001) and plasma carotenoids (p = 0.009) predicted weight loss. This
      demonstrates the efficacy of a weight loss intervention in improving diet quality
      of obese COPD adults.

PMID- 29053576
TI  - Toward "Age-Friendly Slums"? Health Challenges of Older Slum Dwellers in Nairobi
      and the Applicability of the Age-Friendly City Approach.
AB  - A majority of urban residents in sub-Saharan Africa (SSA) and other developing
      regions live in informal settlements, or slums. Much of the discourse on slum
      health centres on younger generations, while an intensifying agenda on healthy
      ageing as yet lacks a systematic focus on slums. Similarly, the global age
      friendly cities (AFC) movement does not, thus far, extend to slums. This paper
      examines the particular challenges that a slum-focused age-friendly initiative in
      SSA may need to address, and the relevance of present AFC indicators and domains
      for initiatives to advance the health and well-being of older slum dwellers. The
      analysis builds on the case of two slum communities in Nairobi, Kenya. It
      analyzes two bodies of relevant evidence from these settlements, namely on the
      health and social circumstances of older residents, and on the local application
      and measurement of AFC indicators. The findings point to a set of unsurprising,
      but also less obvious, core health and social adversities that an age-friendly
      initiative in such settlements would need to consider. The findings show,
      further, that the current AFC domains and indicators framework only partly
      capture these adversities, but that there is potential for adapting the framework
      to be meaningful for slum settings. The paper concludes by underscoring the need
      for, and opportunities inherent in, the pursuit of an "age-friendly slums"
      initiative going forward.

PMID- 29053577
TI  - Electrographic Changes Accompanying Recurrent Seizures under Ketogenic Diet
      Treatment.
AB  - The ketogenic diet (KD) is increasingly used to treat epilepsy refractory to
      antiepileptic drugs and other neurological disorders. In animal models, the KD
      was found to increase the threshold to seizures induced by different convulsive
      stimulations. However, in models in which suprathreshold stimuli were used, a
      paradoxical seizure worsening was consistently observed in KD-fed animals. To
      better define this phenomenon, we characterized the electrographic response to
      seizures induced in mice which were treated with the KD, and then corneally
      stimulated at 6-Hz in four different sessions. We also evaluated the
      electroencephalogram (EEG) in three patients in which the KD was associated with
      a paradoxical worsening of epileptic seizures. Although seizures were initially
      less severe, a remarkable prolongation of the electrographic response was
      observed in mice receiving the KD from the second session of 6-Hz corneal
      stimulation and onwards. The EEG was also markedly altered in the presence of
      progressive seizure aggravation observed in children treated with the KD,
      specifically one affected by Lennox-Gastaut syndrome and two by type I
      lissencephaly,. These results suggest that when seizures are induced or recur
      because of resistance to therapeutic interventions, the KD may change the EEG by
      potentiating the electrographic epileptic activity.

PMID- 29053578
TI  - Treatment with Synthetic Glucocorticoids and the Hypothalamus-Pituitary-Adrenal
      Axis.
AB  - Chronic glucocorticoid (GC) treatment represents a widely-prescribed therapy for
      several diseases in consideration of both anti-inflammatory and immunosuppressive
      activity but, if used at high doses for prolonged periods, it can determine the
      systemic effects characteristic of Cushing's syndrome. In addition to signs and
      symptoms of hypercortisolism, patients on chronic GC therapy are at risk to
      develop tertiary adrenal insufficiency after the reduction or the withdrawal of
      corticosteroids or during acute stress. This effect is mediated by the negative
      feedback loop on the hypothalamus-pituitary-adrenal (HPA) axis, which mainly
      involves corticotropin-release hormone (CRH), which represents the most important
      driver of adrenocorticotropic hormone (ACTH) release. In fact, after withdrawal
      of chronic GC treatment, reactivation of CRH secretion is a necessary
      prerequisite for the recovery of the HPA axis. In addition to the well-known
      factors which regulate the degree of inhibition of the HPA during synthetic GC
      therapy (type of compound, method of administration, cumulative dose, duration of
      the treatment, concomitant drugs which can increase the bioavailability of GCs),
      there is a considerable variation in individual physiology, probably related to
      different genetic profiles which regulate GC receptor activity. This may
      represent an interesting basis for possible future research fields.

PMID- 29053580
TI  - Study of the Photodynamic Activity of N-Doped TiO2 Nanoparticles Conjugated with
      Aluminum Phthalocyanine.
AB  - TiO2 nanoparticles modified with phthalocyanines (Pc) have been proven to be a
      potential photosensitizer in the application of photodynamic therapy (PDT).
      However, the generation of reactive oxygen species (ROS) by TiO2 nanoparticles
      modified with Pc has not been demonstrated clearly. In this study, nitrogen-doped
      TiO2 conjugated with Pc (N-TiO2-Pc) were studied by means of monitoring the
      generation of ROS. The absorbance and photokilling effect on HeLa cells upon
      visible light of different regions were also studied and compared with non-doped
      TiO2-Pc and Pc. Both N-TiO2-Pc and TiO2-Pc can be activated by visible light and
      exhibited much higher photokilling effect on HeLa cells than Pc. In addition,
      nitrogen-doping can greatly enhance the formation of 1O2 and *O2-, while it
      suppresses the generation of OH*. This resulted in significant photodynamic
      activity. Therefore, N-TiO2-Pc can be an excellent candidate for a
      photosensitizer in PDT with wide-spectrum visible irradiation.

PMID- 29053581
TI  - The Light Node Communication Framework: A New Way to Communicate Inside Smart
      Homes.
AB  - The Internet of things has profoundly changed the way we imagine information
      science and architecture, and smart homes are an important part of this domain.
      Created a decade ago, the few existing prototypes use technologies of the day,
      forcing designers to create centralized and costly architectures that raise some
      issues concerning reliability, scalability, and ease of access which cannot be
      tolerated in the context of assistance. In this paper, we briefly introduce a new
      kind of architecture where the focus is placed on distribution. More
      specifically, we respond to the first issue we encountered by proposing a
      lightweight and portable messaging protocol. After running several tests, we
      observed a maximized bandwidth, whereby no packets were lost and good encryption
      was obtained. These results tend to prove that our innovation may be employed in
      a real context of distribution with small entities.

PMID- 29053579
TI  - Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy.
AB  - Recent years have seen considerable progress in explaining the mechanisms of the
      pathogenesis of psoriasis, with a significant role played in it by the hyper
      reactivity of Th1 and Th17 cells, Treg function disorder, as well as complex
      relationships between immune cells, keratinocytes, and vascular endothelium. The
      effect of stem cells in the epidermis and stem cells on T cells has been
      identified and the dysfunction of various types of stem cells may be a prime
      cause of dysregulation of the inflammatory response in psoriasis. However,
      exploring these mechanisms in detail could provide a chance to develop new
      therapeutic strategies. In this paper, the authors reviewed data on the role
      played by stem cells in the pathogenesis of psoriasis and initial attempts at
      using them in treatment.

PMID- 29053582
TI  - Zinc Supplementation Improves Glucose Homeostasis in High Fat-Fed Mice by
      Enhancing Pancreatic beta-Cell Function.
AB  - Zinc is an essential component of the insulin granule and it possibly modulates
      insulin secretion and signaling. Since insulin resistance is a hallmark in the
      development of type 2 diabetes mellitus, this study aimed at investigating if
      zinc supplementation is able to improve glucose tolerance and beta-cell function
      in a model of insulin resistance. Male C57BL/6 mice were distributed in four
      groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl2
      (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl2 (HFZ).
      Intraperitoneal glucose (ipGTT) and insulin (ipITT) tolerance, glycemia,
      insulinemia, HOMA-IR, and HOMA-beta were determined after 15 weeks in each diet.
      Glucose-stimulated insulin secretion (GSIS) was investigated in isolated islets.
      The insulin effect on glucose uptake, metabolism, and signaling was investigated
      in soleus muscle. ZnCl2 did not affect body mass or insulin sensitivity as
      assessed by ipITT, HOMA-IR, muscle glucose metabolism, and Akt and GSK3-beta
      phosphorylation. However, glucose tolerance, HOMA-beta, and GSIS were
      significantly improved by ZnCl2 supplementation. Therefore, ZnCl2 supplementation
      improves glucose homeostasis in high fat-fed mice by a mechanism that enhances
      beta-cell function, rather than whole-body or muscle insulin sensitivity.

PMID- 29053583
TI  - Body Weight Cycling with Identical Diet Composition Does Not Affect Energy
      Balance and Has No Adverse Effect on Metabolic Health Parameters.
AB  - BACKGROUND: Body weight (BW) cycling, the yo-yo effect, is generally thought to
      have adverse effects on human metabolic health. However, human and animal
      experiments are limited in number and do not provide clear answers, partly due to
      large variations in experimental design, parameters measured, and definitions of
      BW cycling. Here, we examined the effect of repetitive BW cycling versus single-
      and non-cycling control groups, without alterations in diet composition, on
      steady state BW and metabolic parameters. METHODS: We induced well-defined BW
      cycles on a semi-purified high fat diet in C57BL/6J mice, a well-described animal
      model for diet-induced obesity, and measured energy expenditure and relevant
      metabolic parameters. RESULTS: Our setup indeed resulted in the intended BW
      changes and always reached a stage of energy balance. A history of weight cycling
      did not result in increased BW or fat mass compared with the control group, nor
      in deteriorated serum concentrations of glucose, adipokines and serum
      triglyceride and free fatty acid (FFA) concentrations. If anything, BW tended to
      be reduced, presumably because of a reduced overall energy intake in BW cycling
      animals. CONCLUSION: Repeated cycling in BW without changes in diet composition
      does not lead to impaired metabolic health nor increased BW (gain).

PMID- 29053584
TI  - Lomefloxacin Induces Oxidative Stress and Apoptosis in COLO829 Melanoma Cells.
AB  - Although some fluoroquinolones have been found to exert anti-tumor activity,
      studies on the effect of these drugs on melanoma cells are relatively rare. The
      aim of this study was to examine the effect of lomefloxacin on cell viability,
      reactive oxygen species production, redox balance, cell cycle distribution, DNA
      fragmentation, and apoptosis in COLO829 melanoma cells. Lomefloxacin decreases
      the cell viability in a dose- and time-dependent manner. For COLO829 cells
      treated with the drug for 24, 48, and 72 h, the values of IC50 were found to be
      0.51, 0.33, and 0.25 mmol/L, respectively. The analyzed drug also altered the
      redox signaling pathways, as shown by intracellular reactive oxygen species
      overproduction and endogeneous glutathione depletion. After lomefloxacin
      treatment, the cells were arrested in S- and G2/M-phase, suggesting a mechanism
      related to topoisomerase II inhibition. DNA fragmentation was observed when the
      cells were exposed to increasing lomefloxacin concentrations and a prolongation
      of incubation time. Moreover, it was demonstrated that the drug induced
      mitochondrial membrane breakdown as an early hallmark of apoptosis. The obtained
      results provide a strong molecular basis for the pharmacologic effect underlying
      the potential use of lomefloxacin as a valuable agent for the treatment of
      melanoma in vivo.

PMID- 29053585
TI  - Companion Plants for Aphid Pest Management.
AB  - A potential strategy for controlling pests is through the use of "companion
      plants" within a crop system. This strategy has been used in several trials to
      fight against a major crop insect pest: the aphid. We reviewed the literature to
      highlight the major mechanisms by which a companion plant may act. Trials carried
      out under laboratory or field conditions revealed that companion plants operate
      through several mechanisms. A companion plant may be associated with a target
      crop for various reasons. Firstly, it can attract aphids and draw them away from
      their host plants. Secondly, it can alter the recognition of the host plant. This
      effect is mostly attributed to companion plant volatiles since they disturb the
      aphid host plant location, and additionally they may react chemically and
      physiologically with the host plant, making it an unsuitable host for aphids.
      Thirdly, it can attract natural enemies by providing shelter and food resources.
      In this review, the feasibility of using companion plants is discussed. We
      conclude that many factors need to be taken into account for a successful
      companion plant strategy. For the best long-term results, companion plant
      strategies have to be combined with other alternative approaches against aphids.

PMID- 29053586
TI  - Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles
      Tendons after Acute Rupture.
AB  - A balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs)
      is required to maintain tendon homeostasis. Variation in this balance over time
      might impact on the success of tendon healing. This study aimed to analyze
      structural changes and the expression profile of MMPs and TIMPs in human Achilles
      tendons at different time-points after rupture. Biopsies from 37 patients with
      acute Achilles tendon rupture were taken at surgery and grouped according to time
      after rupture: early (2-4 days), middle (5-6 days), and late (>=7 days), and
      intact Achilles tendons served as control. The histological score increased from
      the early to the late time-point after rupture, indicating the progression
      towards a more degenerative status. In comparison to intact tendons, qRT-PCR
      analysis revealed a significantly increased expression of MMP-1, -2, -13, TIMP-1,
      COL1A1, and COL3A1 in ruptured tendons, whereas TIMP-3 decreased. Comparing the
      changes over time post rupture, the expression of MMP-9, -13, and COL1A1
      significantly increased, whereas MMP-3 and -10 expression decreased. TIMP
      expression was not significantly altered over time. MMP staining by
      immunohistochemistry was positive in the ruptured tendons exemplarily analyzed
      from early and late time-points. The study demonstrates a pivotal contribution of
      all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the
      early human tendon healing process.

PMID- 29053587
TI  - Heat-Responsive Photosynthetic and Signaling Pathways in Plants: Insight from
      Proteomics.
AB  - Heat stress is a major abiotic stress posing a serious threat to plants. Heat
      responsive mechanisms in plants are complicated and fine-tuned. Heat signaling
      transduction and photosynthesis are highly sensitive. Therefore, a thorough
      understanding of the molecular mechanism in heat stressed-signaling transduction
      and photosynthesis is necessary to protect crop yield. Current high-throughput
      proteomics investigations provide more useful information for underlying heat
      responsive signaling pathways and photosynthesis modulation in plants. Several
      signaling components, such as guanosine triphosphate (GTP)-binding protein,
      nucleoside diphosphate kinase, annexin, and brassinosteroid-insensitive I-kinase
      domain interacting protein 114, were proposed to be important in heat signaling
      transduction. Moreover, diverse protein patterns of photosynthetic proteins imply
      that the modulations of stomatal CO2 exchange, photosystem II, Calvin cycle, ATP
      synthesis, and chlorophyll biosynthesis are crucial for plant heat tolerance.

PMID- 29053588
TI  - Yeast Killer Toxin K28: Biology and Unique Strategy of Host Cell Intoxication and
      Killing.
AB  - The initial discovery of killer toxin-secreting brewery strains of Saccharomyces
      cerevisiae (S. cerevisiae) in the mid-sixties of the last century marked the
      beginning of intensive research in the yeast virology field. So far, four
      different S. cerevisiae killer toxins (K28, K1, K2, and Klus), encoded by
      cytoplasmic inherited double-stranded RNA viruses (dsRNA) of the Totiviridae
      family, have been identified. Among these, K28 represents the unique example of a
      yeast viral killer toxin that enters a sensitive cell by receptor-mediated
      endocytosis to reach its intracellular target(s). This review summarizes and
      discusses the most recent advances and current knowledge on yeast killer toxin
      K28, with special emphasis on its endocytosis and intracellular trafficking,
      pointing towards future directions and open questions in this still timely and
      fascinating field of killer yeast research.

PMID- 29053589
TI  - Structural and Functional Insight into Canarypox Virus CNP058 Mediated Regulation
      of Apoptosis.
AB  - Programmed cell death or apoptosis is an important component of host defense
      systems against viral infection. The B-cell lymphoma 2 (Bcl-2) proteins family is
      the main arbiter of mitochondrially mediated apoptosis, and viruses have evolved
      sequence and structural mimics of Bcl-2 to subvert premature host cell apoptosis
      in response to viral infection. The sequencing of the canarypox virus genome
      identified a putative pro-survival Bcl-2 protein, CNP058. However, a role in
      apoptosis inhibition for CNP058 has not been identified to date. Here, we report
      that CNP058 is able to bind several host cell pro-death Bcl-2 proteins, including
      Bak and Bax, as well as several BH3 only-proteins including Bim, Bid, Bmf, Noxa,
      Puma, and Hrk with high to moderate affinities. We then defined the structural
      basis for CNP058 binding to pro-death Bcl-2 proteins by determining the crystal
      structure of CNP058 bound to Bim BH3. CNP058 adopts the conserved Bcl-2 like fold
      observed in cellular pro-survival Bcl-2 proteins, and utilizes the canonical
      ligand binding groove to bind Bim BH3. We then demonstrate that CNP058 is a
      potent inhibitor of ultraviolet (UV) induced apoptosis in a cell culture model.
      Our findings suggest that CNP058 is a potent inhibitor of apoptosis that is able
      to bind to BH3 domain peptides from a broad range of pro-death Bcl-2 proteins,
      and may play a key role in countering premature host apoptosis.

PMID- 29053590
TI  - Land Use Regression Modeling of Outdoor Noise Exposure in Informal Settlements in
      Western Cape, South Africa.
AB  - In low- and middle-income countries, noise exposure and its negative health
      effects have been little explored. The present study aimed to assess the noise
      exposure situation in adults living in informal settings in the Western Cape
      Province, South Africa. We conducted continuous one-week outdoor noise
      measurements at 134 homes in four different areas. These data were used to
      develop a land use regression (LUR) model to predict A-weighted day-evening-night
      equivalent sound levels (Lden) from geographic information system (GIS)
      variables. Mean noise exposure during day (6:00-18:00) was 60.0 A-weighted
      decibels (dB(A)) (interquartile range 56.9-62.9 dB(A)), during night (22:00-6:00)
      52.9 dB(A) (49.3-55.8 dB(A)) and average Lden was 63.0 dB(A) (60.1-66.5 dB(A)).
      Main predictors of the LUR model were related to road traffic and household
      density. Model performance was low (adjusted R2 = 0.130) suggesting that other
      influences than those represented in the geographic predictors are relevant for
      noise exposure. This is one of the few studies on the noise exposure situation in
      low- and middle-income countries. It demonstrates that noise exposure levels are
      high in these settings.

PMID- 29053591
TI  - Real-Time Monitoring of Water Content in Sandy Soil Using Shear Mode Piezoceramic
      Transducers and Active Sensing-A Feasibility Study.
AB  - A quantitative understanding of soil water content or soil water status is of
      great importance to many applications, such as landslide monitoring, rockfill dam
      health monitoring, precision agriculture, etc. In this paper, a feasibility study
      was conducted to monitor the soil water content in real time using permanent
      embedded piezoceramic-based transducers called smart aggregates (SAs). An active
      sensing approach using a customized swept acoustic wave with a frequency range
      between 100 Hz and 300 kHz was used to study the wave attenuation in the soil in
      correlation to soil moisture levels. Two sandy soil specimens, each embedded with
      a pair of SAs, were made in the laboratory, and the water percentage of the soil
      specimens was incrementally decreased from 15% to 3% during the tests. Due to the
      change of the soil water status, the damping property of the soil correspondingly
      changes. The change of the damping property results in the variation of the
      acoustic wave attenuation ratios. A wavelet packet-based energy index was adopted
      to compute the energy of the signal captured by the SA sensor. Experimental
      results show a parabolic growth curve of the received signal energy vs. the water
      percentage of the soil. The feasibility, sensitivity, and reliability of the
      proposed method for in-situ monitoring of soil water status were discussed.

PMID- 29053593
TI  - Synthesis and Characterization of TiO2 Nanoparticles for the Reduction of Water
      Pollutants.
AB  - The aim of this manuscript was the optimization of the synthesis of TiO2
      nanoparticles (TiO2 NPs) with conditions that could be easily reproducible at the
      industrial level. Several procedures were tested and those with C12H28O4Ti and
      CO(NH2)2 as precursors seemed the most promising and, consequently, were improved
      with different molar ratios, lower temperatures and the addition of NH4Cl as a
      secondary dopant of nitrogen. The obtained samples were studied with analytical
      techniques such as X-ray powder diffraction (XRPD) and field emission scanning
      electron microscopy (FESEM). To complete the study, dye degradation and
      bacteriological tests were also performed. The results indicate that it is
      possible to obtain TiO2 NPs at lower temperatures with respect to those used in
      the literature; the best candidate that could satisfy all the requirements was a
      sample with a molar ratio of C12H28O4Ti:CO(NH2)2 at 2:1 and obtained at 50 
      degrees C.

PMID- 29053592
TI  - Platelets and Multi-Organ Failure in Sepsis.
AB  - Platelets have received increasing attention for their role in the
      pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a
      low platelet count is a well-known biomarker for disease severity and more
      recently authors have focused their attention on the active role of platelets in
      the pathogenesis of multi-organ failure. Septic shock is characterised by a
      dysregulated inflammatory response, which can impair the microcirculation and
      lead to organ injury. Being at the crossroads between the immune system, clotting
      cascade, and endothelial cells, platelets seem to be an appealing central
      mediator and possible therapeutic target in sepsis. This review focuses on the
      pathogenic role of platelets in septic organ dysfunction in humans and animal
      models.

PMID- 29053594
TI  - Chronic Exposure to the Fusarium Mycotoxin Deoxynivalenol: Impact on Performance,
      Immune Organ, and Intestinal Integrity of Slow-Growing Chickens.
AB  - This study investigates the long-term effects of deoxynivalenol (DON) consumption
      on avian growth performance, on the proliferation, apoptosis, and DNA damage of
      spleen cells, and on intestinal integrity. Two hundred and eight 5-day-old black
      feathered Taiwan country chickens were fed diets containing 0, 2, 5, and 10 mg/kg
      of DON for 16 weeks. Body weight gain of male birds in the 2 mg/kg group was
      significantly lower than that in the 5 mg/kg group. At the end of trial, feeding
      DON-contaminated diets of 5 mg/kg resulted in heavier spleens. Moreover, the
      increase in DON induced cellular proliferation, apoptosis, and DNA damage signals
      in the spleen, the exception being female birds fed 10 mg/kg of DON showing
      reduced proliferation. Expression of claudin-5 was increased in jejunum of female
      birds fed 2 and 5 mg/kg of DON, whereas decreased expression levels were found in
      male birds. In conclusion, our results verified that DON may cause a disturbance
      to the immune system and alter the intestinal barrier in Taiwan country chickens,
      and may also lead to discrepancies in growth performances in a dose- and sex
      dependent manner.

PMID- 29053595
TI  - Magnetic Properties of Fibonacci-Modulated Fe-Au Multilayer Metamaterials.
AB  - Herein we experimentally study magnetic multilayer metamaterials with broken
      translational symmetry. Epitaxially-grown iron-gold (Fe-Au) multilayers modulated
      using Fibonacci sequence-referred to as magnetic inverse Fibonacci-modulated
      multilayers (IFMs)-are prepared using ultra-high-vacuum vapor deposition.
      Experimental results of in-situ reflection high-energy electron diffraction,
      magnetization curves, and ferromagnetic resonance demonstrate that the
      epitaxially-grown Fe-Au IFMs have quasi-isotropic magnetization, in contrast to
      the in-plane magnetization easy axis in the periodic multilayers.

PMID- 29053597
TI  - Time-Variant Reliability Analysis for Rubber O-Ring Seal Considering Both
      Material Degradation and Random Load.
AB  - Due to the increase in working hours, the reliability of rubber O-ring seals used
      in hydraulic systems of transfer machines will change. While traditional methods
      can only analyze one of the material properties or seal properties, the failure
      of the O-ring is caused by these two factors together. In this paper, two factors
      are mainly analyzed: the degradation of material properties and load
      randomization by processing technology. Firstly, the two factors are defined in
      terms of material failure and seal failure, before the experimental methods of
      rubber materials are studied. Following this, the time-variant material
      properties through experiments and load distribution by monitoring the processing
      can be obtained. Thirdly, compressive stress and contact stress have been
      calculated, which was combined with the reliability model to acquire the time
      variant reliability for the O-ring. Finally, the life prediction and effect of
      oil pressure were discussed, then compared with the actual situation. The results
      show a lifetime of 12 months for the O-ring calculated in this paper, and
      compared with the replacement records from the maintenance workshop, the result
      is credible.

PMID- 29053596
TI  - Elucidating the Role of Host Long Non-Coding RNA during Viral Infection:
      Challenges and Paths Forward.
AB  - Research over the past decade has clearly shown that long non-coding RNAs
      (lncRNAs) are functional. Many lncRNAs can be related to immunity and the host
      response to viral infection, but their specific functions remain largely elusive.
      The vast majority of lncRNAs are annotated with extremely limited knowledge and
      tend to be expressed at low levels, making ad hoc experimentation difficult.
      Changes to lncRNA expression during infection can be systematically profiled
      using deep sequencing; however, this often produces an intractable number of
      candidate lncRNAs, leaving no clear path forward. For these reasons, it is
      especially important to prioritize lncRNAs into high-confidence "hits" by
      utilizing multiple methodologies. Large scale perturbation studies may be used to
      screen lncRNAs involved in phenotypes of interest, such as resistance to viral
      infection. Single cell transcriptome sequencing quantifies cell-type specific
      lncRNAs that are less abundant in a mixture. When coupled with iterative
      experimental validations, new computational strategies for efficiently
      integrating orthogonal high-throughput data will likely be the driver for
      elucidating the functional role of lncRNAs during viral infection. This review
      highlights new high-throughput technologies and discusses the potential for
      integrative computational analysis to streamline the identification of infection
      related lncRNAs and unveil novel targets for antiviral therapeutics.

PMID- 29053598
TI  - L21 and XA Ordering Competition in Hafnium-Based Full-Heusler Alloys Hf2VZ (Z =
      Al, Ga, In, Tl, Si, Ge, Sn, Pb).
AB  - For theoretical designing of full-Heusler based spintroinc materials, people have
      long believed in the so-called Site Preference Rule (SPR). Very recently,
      according to the SPR, there are several studies on XA-type Hafnium-based Heusler
      alloys X2YZ, i.e., Hf2VAl, Hf2CoZ (Z = Ga, In) and Hf2CrZ (Z = Al, Ga, In). In
      this work, a series of Hf2-based Heusler alloys, Hf2VZ (Z = Al, Ga, In, Tl, Si,
      Ge, Sn, Pb), were selected as targets to study the site preferences of their
      atoms by first-principle calculations. It has been found that all of them are
      likely to exhibit the L21-type structure instead of the XA one. Furthermore, we
      reveal that the high values of spin-polarization of XA-type Hf2VZ (Z = Al, Ga,
      In, Tl, Si, Ge, Sn, Pb) alloys have dropped dramatically when they form the L21
      type structure. Also, we prove that the electronic, magnetic, and physics nature
      of these alloys are quite different, depending on the L21-type or XA-type
      structures.

PMID- 29053600
TI  - Detection and Management of Mango Dieback Disease in the United Arab Emirates.
AB  - Mango is affected by different decline disorders causing significant losses to
      mango growers. In the United Arab Emirates (UAE), the pathogen was isolated from
      all tissues sampled from diseased trees affected by Lasiodiplodia theobromae.
      Symptoms at early stages of the disease included general wilting appearance of
      mango trees, and dieback of twigs. In advanced stages, the disease symptoms were
      also characterized by the curling and drying of leaves, leading to complete
      defoliation of the tree and discolouration of vascular regions of the stems and
      branches. To substantially reduce the devastating impact of dieback disease on
      mango, the fungus was first identified based on its morphological and cultural
      characteristics. Target regions of 5.8S rRNA (ITS) and elongation factor 1-alpha
      (EF1-alpha) genes of the pathogen were amplified and sequenced. We also found
      that the systemic chemical fungicides, Score(r), Cidely(r) Top, and
      Penthiopyrad(r), significantly inhibited the mycelial growth of L. theobromae
      both in vitro and in the greenhouse. Cidely(r) Top proved to be a highly
      effective fungicide against L. theobromae dieback disease also under field
      conditions. Altogether, the morphology of the fruiting structures, molecular
      identification and pathogenicity tests confirm that the causal agent of the mango
      dieback disease in the UAE is L. theobromae.

PMID- 29053601
TI  - Modeling and Predicting the Stress Relaxation of Composites with Short and
      Randomly Oriented Fibers.
AB  - The addition of short fibers has been experimentally observed to slow the stress
      relaxation of viscoelastic polymers, producing a change in the relaxation time
      constant. Our recent study attributed this effect of fibers on stress relaxation
      behavior to the interfacial shear stress transfer at the fiber-matrix interface.
      This model explained the effect of fiber addition on stress relaxation without
      the need to postulate structural changes at the interface. In our previous study,
      we developed an analytical model for the effect of fully aligned short fibers,
      and the model predictions were successfully compared to finite element
      simulations. However, in most industrial applications of short-fiber composites,
      fibers are not aligned, and hence it is necessary to examine the time dependence
      of viscoelastic polymers containing randomly oriented short fibers. In this
      study, we propose an analytical model to predict the stress relaxation behavior
      of short-fiber composites where the fibers are randomly oriented. The model
      predictions were compared to results obtained from Monte Carlo finite element
      simulations, and good agreement between the two was observed. The analytical
      model provides an excellent tool to accurately predict the stress relaxation
      behavior of randomly oriented short-fiber composites.

PMID- 29053599
TI  - Gut Fermentation of Dietary Fibres: Physico-Chemistry of Plant Cell Walls and
      Implications for Health.
AB  - The majority of dietary fibre (DF) originates from plant cell walls. Chemically,
      DF mostly comprise carbohydrate polymers, which resist hydrolysis by digestive
      enzymes in the mammalian small intestine, but can be fermented by large
      intestinal bacteria. One of the main benefits of DF relate to its fermentability,
      which affects microbial diversity and function within the gastro-intestinal tract
      (GIT), as well as the by-products of the fermentation process. Much work
      examining DF tends to focus on various purified ingredients, which have been
      extracted from plants. Increasingly, the validity of this is being questioned in
      terms of human nutrition, as there is evidence to suggest that it is the actual
      complexity of DF which affects the complexity of the GIT microbiota. Here, we
      review the literature comparing results of fermentation of purified DF
      substrates, with whole plant foods. There are strong indications that the more
      complex and varied the diet (and its ingredients), the more complex and varied
      the GIT microbiota is likely to be. Therefore, it is proposed that as the DF
      fermentability resulting from this complex microbial population has such profound
      effects on human health in relation to diet, it would be appropriate to include
      DF fermentability in its characterization-a functional approach of immediate
      relevance to nutrition.

PMID- 29053602
TI  - An Objective Balance Error Scoring System for Sideline Concussion Evaluation
      Using Duplex Kinect Sensors.
AB  - Sports-related concussion is a common sports injury that might induce potential
      long-term consequences without early diagnosis and intervention in the field.
      However, there are few options of such sensor systems available. The aim of the
      study is to propose and validate an automated concussion administration and
      scoring approach, which is objective, affordable and capable of detecting all
      balance errors required by the balance error scoring system (BESS) protocol in
      the field condition. Our approach is first to capture human body skeleton
      positions using two Microsoft Kinect sensors in the proposed configuration and
      merge the data by a custom-made algorithm to remove the self-occlusion of limbs.
      The standing balance errors according to BESS protocol were further measured and
      accessed automatically by the proposed algorithm. Simultaneously, the BESS test
      was filmed for scoring by an experienced rater. Two results were compared using
      Pearson coefficient r, obtaining an excellent consistency (r = 0.93, p < 0.05).
      In addition, BESS test-retest was performed after seven days and compared using
      intraclass correlation coefficients (ICC), showing a good test-retest reliability
      (ICC = 0.81, p < 0.01). The proposed approach could be an alternative of
      objective tools to assess postural stability for sideline sports concussion
      diagnosis.

PMID- 29053603
TI  - Clinical and Genetic Evaluation of a Cohort of Pediatric Patients with Severe
      Inherited Retinal Dystrophies.
AB  - We performed a clinical and genetic characterization of a pediatric cohort of
      patients with inherited retinal dystrophy (IRD) to identify the most suitable
      cases for gene therapy. The cohort comprised 43 patients, aged between 2 and 18
      years, with severe isolated IRD at the time of presentation. The ophthalmological
      characterization also included assessment of the photoreceptor layer integrity in
      the macular region (ellipsoid zone (EZ) band). In parallel, we carried out a
      targeted, next-generation sequencing (NGS)-based analysis using a panel that
      covers over 150 genes with either an established or a candidate role in IRD
      pathogenesis. Based on the ophthalmological assessment, the cohort was composed
      of 24 Leber congenital amaurosis, 14 early onset retinitis pigmentosa, and 5
      achromatopsia patients. We identified causative mutations in 58.1% of the cases.
      We also found novel genotype-phenotype correlations in patients harboring
      mutations in the CEP290 and CNGB3 genes. The EZ band was detectable in 40% of the
      analyzed cases, also in patients with genotypes usually associated with severe
      clinical manifestations. This study provides the first detailed clinical-genetic
      assessment of severe IRDs with infantile onset and lays the foundation of a
      standardized protocol for the selection of patients that are more likely to
      benefit from gene replacement therapeutic approaches.

PMID- 29053605
TI  - Flexible Sensors for Pressure Therapy: Effect of Substrate Curvature and
      Stiffness on Sensor Performance.
AB  - Flexible pressure sensors are increasingly being used in medical and non-medical
      applications, and particularly in innovative health monitoring. Their efficacy in
      medical applications such as compression therapy depends on the accuracy and
      repeatability of their output, which in turn depend on factors such as sensor
      type, shape, pressure range, and conformability of the sensor to the body
      surface. Numerous researchers have examined the effects of sensor type and shape,
      but little information is available on the effect of human body parameters such
      as support surfaces' curvature and the stiffness of soft tissues on pressure
      sensing performance. We investigated the effects of body parameters on the
      performance of pressure sensors using a custom-made human-leg-like test setup.
      Pressure sensing parameters such as accuracy, drift and repeatability were
      determined in both static (eight hours continuous pressure) and dynamic (10
      cycles of pressure application of 30 s duration) testing conditions. The testing
      was performed with a focus on compression therapy application for venous leg
      ulcer treatments, and was conducted in a low-pressure range of 20-70 mmHg.
      Commercially available sensors manufactured by Peratech and Sensitronics were
      used under various loading conditions to determine the influence of stiffness and
      curvature. Flat rigid, flat soft silicone and three cylindrical silicone surfaces
      of radii of curvature of 3.5 cm, 5.5 cm and 6.5 cm were used as substrates under
      the sensors. The Peratech sensor averaged 94% accuracy for both static and
      dynamic measurements on all substrates; the Sensitronics sensor averaged 88%
      accuracy. The Peratech sensor displayed moderate variations and the Sensitronics
      sensor large variations in output pressure readings depending on the underlying
      test surface, both of which were reduced markedly by individual pressure
      calibration for surface type. Sensor choice and need for calibration to surface
      type are important considerations for their application in healthcare monitoring.

PMID- 29053604
TI  - Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations
      with Metabolic Disorders.
AB  - Communities eating a western-like diet, rich in fat, sugar and significantly
      deprived of fibers, share a relevant increased risk of both metabolic and
      cancerous diseases. Even more remarkable is that a low-fiber diet lacks some key
      components-as phytates and inositols-for which a mechanistic link has been
      clearly established in the pathogenesis of both cancer and metabolic illness.
      Reduced bioavailability of inositol in living organisms could arise from reduced
      food supply or from metabolism deregulation. Inositol deregulation has been found
      in a number of conditions mechanistically and epidemiologically associated to
      high-glucose diets or altered glucose metabolism. Indeed, high glucose levels
      hinder inositol availability by increasing its degradation and by inhibiting both
      myo-Ins biosynthesis and absorption. These underappreciated mechanisms may likely
      account for acquired, metabolic deficiency in inositol bioavailability.

PMID- 29053606
TI  - Lung Toxicity of Condensed Aerosol from E-CIG Liquids: Influence of the Flavor
      and the In Vitro Model Used.
AB  - The diffusion of e-cigarette (e-CIG) opens a great scientific and regulatory
      debate about its safety. The huge number of commercialized devices, e-liquids
      with almost infinite chemical formulations and the growing market demand for a
      rapid and efficient toxicity screen system that is able to test all of these
      references and related aerosols. A consensus on the best protocols for the e-CIG
      safety assessment is still far to be achieved, since the huge number of variables
      characterizing these products (e.g., flavoring type and concentration, nicotine
      concentration, type of the device, including the battery and the atomizer). This
      suggests that more experimental evidences are needed to support the regulatory
      frameworks. The present study aims to contribute in this field by testing the
      effects of condensed aerosols (CAs) from three main e-liquid categories (tobacco,
      mint, and cinnamon as food-related flavor), with (18 mg/mL) or without nicotine.
      Two in vitro models, represented by a monoculture of human epithelial alveolar
      cells and a three-dimensional (3D) co-culture of alveolar and lung microvascular
      endothelial cells were used. Cell viability, pro-inflammatory cytokines release
      and alveolar-blood barrier (ABB) integrity were investigated as inhalation
      toxicity endpoints. Results showed that nicotine itself had almost no influence
      on the modulation of the toxicity response, while flavor composition did have.
      The cell viability was significantly decreased in monoculture and ABB after
      exposure to the mints and cinnamon CAs. The barrier integrity was significantly
      affected in the ABB after exposure to cytotoxic CAs. With the exception of the
      significant IL-8 release in the monoculture after Cinnamon exposure, no increase
      of inflammatory cytokines (IL-8 and MCP-1) release was observed. These findings
      point out that multiple assays with different in vitro models are able to
      discriminate the acute inhalation toxicity of CAs from liquids with different
      flavors, providing the companies and regulatory bodies with useful tools for the
      preliminary screening of marketable products.

PMID- 29053607
TI  - Does Migration Limit the Effect of Health Insurance on Hypertension Management in
      China?
AB  - Background: In China, rapid urbanization has caused migration from rural to urban
      areas, and raised the prevalence of hypertension. However, public health
      insurance is not portable from one place to another, and migration may limit the
      effectiveness of this non-portable health insurance on healthcare. Our study aims
      to investigate whether migration limits the effectiveness of health insurance on
      hypertension management in China. Methods: Data were obtained from the national
      baseline survey of the China Health and Retirement Longitudinal Study in 2011,
      including 4926 hypertensive respondents with public health insurance. Outcome
      measures included use of primary care, hypertension awareness, medication use,
      blood pressure monitoring, physician advice, and blood pressure control.
      Multivariate logistic regressions were estimated to examine whether the effects
      of rural health insurance on hypertension management differed between those who
      migrated to urban areas and those who did not migrate and lived in rural areas.
      Results: Among hypertensive respondents, 60.7% were aware of their hypertensive
      status. Compared to rural residents, the non-portable feature of rural health
      insurance significantly reduced rural-to-urban migrants' probabilities of using
      primary care by 7.8 percentage points, hypertension awareness by 8.8 percentage
      points, and receiving physician advice by 18.3 percentage points. Conclusions: In
      China, migration to urban areas limited the effectiveness of rural health
      insurance on hypertension management due to its non-portable nature. It is
      critical to improve the portability of rural health insurance, and to extend
      urban health insurance and primary care coverage to rural-to-urban migrants to
      achieve better chronic disease management.

PMID- 29053608
TI  - The Multi-Parameter Wireless Sensing System (MPwise): Its Description and
      Application to Earthquake Risk Mitigation.
AB  - The Multi-Parameter Wireless Sensing (MPwise) system is an innovative
      instrumental design that allows different sensor types to be combined with
      relatively high-performance computing and communications components. These units,
      which incorporate off-the-shelf components, can undertake complex information
      integration and processing tasks at the individual unit or node level (when used
      in a network), allowing the establishment of networks that are linked by
      advanced, robust and rapid communications routing and network topologies. The
      system (and its predecessors) was originally designed for earthquake risk
      mitigation, including earthquake early warning (EEW), rapid response actions,
      structural health monitoring, and site-effect characterization. For EEW, MPwise
      units are capable of on-site, decentralized, independent analysis of the recorded
      ground motion and based on this, may issue an appropriate warning, either by the
      unit itself or transmitted throughout a network by dedicated alarming procedures.
      The multi-sensor capabilities of the system allow it to be instrumented with
      standard strong- and weak-motion sensors, broadband sensors, MEMS (namely
      accelerometers), cameras, temperature and humidity sensors, and GNSS receivers.
      In this work, the MPwise hardware, software and communications schema are
      described, as well as an overview of its possible applications. While focusing on
      earthquake risk mitigation actions, the aim in the future is to expand its
      capabilities towards a more multi-hazard and risk mitigation role. Overall,
      MPwise offers considerable flexibility and has great potential in contributing to
      natural hazard risk mitigation.

PMID- 29053609
TI  - Renal Cell Tumors: Understanding Their Molecular Pathological Epidemiology and
      the 2016 WHO Classification.
AB  - Accumulating evidence suggests that renal cell tumors represent a group of
      histologically and molecularly heterogeneous diseases, even within the same
      histological subtype. In accordance with the increased understanding of the
      morphological, immunohistochemical, molecular, and epidemiological
      characteristics of renal cell tumors, the World Health Organization (WHO)
      classification of renal cell tumors has been modified. This review provides
      perspectives on both new and current subtypes of renal cell tumors, as well as on
      the emerging/provisional renal cell carcinomas in the new 2016 WHO
      classification, which focuses on features of their molecular pathological
      epidemiology. The WHO classification will require additional revisions to enable
      the classification of renal cell tumors as clinically meaningful subtypes and
      provide a better understanding of the unique characteristics of renal cell
      tumors.

PMID- 29053610
TI  - Lab-on-Chip, Surface-Enhanced Raman Analysis by Aerosol Jet Printing and Roll-to
      Roll Hot Embossing.
AB  - Surface-enhanced Raman spectroscopy (SERS) combines the high specificity of Raman
      scattering with high sensitivity due to an enhancement of the electromagnetic
      field by metallic nanostructures. However, the tyical fabrication methods of SERS
      substrates suffer from low throughput and therefore high costs. Furthermore,
      point-of-care applications require the investigation of liquid solutions and thus
      the integration of the SERS substrate in a microfluidic chip. We present a roll
      to-roll fabrication approach for microfluidics with integrated, highly efficient,
      surface-enhanced Raman scattering structures. Microfluidic channels are formed
      using roll-to-roll hot embossing in polystyrene foil. Aerosol jet printing of a
      gold nanoparticle ink is utilized to manufacture highly efficient, homogeneous,
      and reproducible SERS structures. The modified channels are sealed with a solvent
      free, roll-to-roll, thermal bonding process. In continuous flow measurements,
      these chips overcome time-consuming incubation protocols and the poor
      reproducibility of SERS experiments often caused by inhomogeneous drying of the
      analyte. In the present study, we explore the influence of the printing process
      on the homogeneity and the enhancement of the SERS structures. The feasibility of
      aerosol-jet-modified microfluidic channels for highly sensitive SERS detection is
      demonstrated by using solutions with different concentrations of Rhodamine 6G and
      adenosine. The printed areas provide homogeneous enhancement factors of ~4 * 106.
      Our work shows a way towards the low-cost production of tailor-made, SERS
      enabled, label-free, lab-on- chip systems for bioanalysis.

PMID- 29053611
TI  - Glucosylsphingosine Causes Hematological and Visceral Changes in Mice-Evidence
      for a Pathophysiological Role in Gaucher Disease.
AB  - Glucosylceramide and glucosylsphingosine are the two major storage products in
      Gaucher disease (GD), an inherited metabolic disorder caused by a deficiency of
      the lysosomal enzyme glucocerebrosidase. The build-up of glucosylceramide in the
      endoplasmic reticulum and prominent accumulation in cell lysosomes of tissue
      macrophages results in decreased blood cell and platelet counts, and skeletal
      abnormalities. The pathological role of the deacylated form of glucosylceramide,
      glucosylsphingosine (lyso-Gb1), a recently identified sensitive and specific
      biomarker for GD, is not well investigated. We established a long-term infusion
      model in C57BL/6JRj mice to examine the effect of lyso-Gb1 on representative
      hallmark parameters of GD. Mice received lyso-Gb1 at a dosage of 10 mg.kg-1 per
      day as a continuous subcutaneous administration, and were routinely checked for
      blood lyso-Gb1 levels using liquid chromatography-multiple reaction monitoring
      mass spectrometry (LC/MRM-MS) measurements at four-weekly intervals throughout
      treatment. The C57BL/6JRj mice showed a stable increase of lyso-Gb1 up to->500
      fold greater than the normal reflecting concentrations seen in moderately to
      severely affected patients. Furthermore, lyso-Gb1 accumulated in peripheral
      tissues. The mice developed hematological symptoms such as reduced hemoglobin and
      hematocrit, increased spleen weights and a slight inflammatory tissue response
      after eight weeks of treatment. The above findings indicate a measurable visceral
      and hematological response in treated mice that suggests a role for lyso-Gb1 in
      the development of peripheral signs of GD.

PMID- 29053612
TI  - In Search of Consistent Predictors of Children's Physical Activity.
AB  - Physical activity is pivotal for children's health and well-being, yet
      participation declines across teenage years. Efforts to increase physical
      activity need to be strengthened to combat this, however, evidence for the design
      and planning of physical activity promotion in children is lacking. The aim was
      to identify predictors of physical activity that were relatively consistent
      across three different measures of physical activity, in pre- and early
      adolescent South Australians. This is the first study to compare correlates of
      physical activity across three measures of physical activity in a single sample,
      in this age group. Children (n = 324) aged 9-13 years and their parents were
      surveyed on personal, interpersonal and environmental correlates of physical
      activity. Child physical activity was objectively measured using pedometers (7
      days). Self-reported physical activity was determined from organised sport
      participation and the Physical Activity Questionnaire for Adolescents. Regression
      models were used to identify consistent predictors of three physical activity
      measures. Consistent predictors across multiple physical activity measures were:
      parent support for physical activity, having appropriate clothing for sport,
      enjoyment of physical activity and perceived availability of sporting clubs.
      These predictors identify potential avenues for directing intervention efforts to
      increase physical activity in early adolescents.

PMID- 29053613
TI  - Advances in Biomarkers for PCa Diagnostics and Prognostics-A Way towards
      Personalized Medicine.
AB  - Prostate cancer (PCa) is, with an estimated number of 161,360 cases and 26,730
      deaths in 2017, the most common malignancy in the USA [...].

PMID- 29053614
TI  - Crack Monitoring Method for an FRP-Strengthened Steel Structure Based on an
      Antenna Sensor.
AB  - Fiber-reinforced polymer (FRP) has been increasingly applied to steel structures
      for structural strengthening or crack repair, given its high strength-to-weight
      ratio and high stiffness-to-weight ratio. Cracks in steel structures are the
      dominant hidden threats to structural safety. However, it is difficult to monitor
      structural cracks under FRP coverage and there is little related research. In
      this paper, a crack monitoring method for an FRP-strengthened steel structure
      deploying a microstrip antenna sensor is presented. A theoretical model of the
      dual-substrate antenna sensor with FRP is established and the sensitivity of
      crack monitoring is studied. The effects of the weak conductivity of carbon fiber
      reinforced polymers (CFRPs) on the performance of crack monitoring are analyzed
      via contrast experiments. The effects of FRP thickness on the performance of the
      antenna sensor are studied. The influence of structural strain on crack detection
      coupling is studied through strain-crack coupling experiments. The results
      indicate that the antenna sensor can detect cracks in steel structures covered by
      FRP (including CFRP). FRP thickness affects the antenna sensor's performance
      significantly, while the effects of strain can be ignored. The results provide a
      new approach for crack monitoring of FRP-strengthened steel structures with
      extensive application prospects.

PMID- 29053615
TI  - Residue Dynamics and Risk Assessment of Prochloraz and Its Metabolite 2,4,6
      Trichlorophenol in Apple.
AB  - The residue dynamics and risk assessment of prochloraz and its metabolite 2,4,6
      trichlorophenol (2,4,6-TCP) in apple under different treatment concentrations
      were investigated using a GC-ECD method. The derivatization percent of prochloraz
      to 2,4,6-TCP was stable and complete. The recoveries of prochloraz and 2,4,6-TCP
      were 82.9%-114.4%, and the coefficients of variation (CV) were 0.7%-8.6% for the
      whole fruit, apple pulp, and apple peel samples. Under the application of 2 
      degrees C 2.0 g/L, 2  degrees C 1.0 g/L, 20  degrees C 2.0 g/L, and 20  degrees C
      1.0 g/L treatment, the half-life for the degradation of prochloraz was 57.8-86.6
      d in the whole fruit and apple peel, and the prochloraz concentration in the
      apple pulp increased gradually until a peak (0.72 mg.kg-1) was reached. The
      concentration of 2,4,6-TCP was below 0.1 mg.kg-1 in four treatment conditions and
      not detected (<LOD) in apple pulp. Finally, based on the detection of market
      samples in Hefei (China), we believe that the residual level of prochloraz in
      apples meets the requirements of the Chinese standards.

PMID- 29053616
TI  - Valorization Challenges to Almond Residues: Phytochemical Composition and
      Functional Application.
AB  - Almond is characterized by its high nutritional value; although information
      reported so far mainly concerns edible kernel. Even though the nutritional and
      commercial relevance of the almond is restricted to almond meat; to date;
      increasing attention has been paid to other parts of this fruit (skin; shell; and
      hull); considered by-products that are scarcely characterized and exploited
      regarding their properties as valuable sources of bioactive compounds (mainly
      represented by phenolic acids and flavonoids). This lack of proper valorization
      procedures entails the continuation of the application of traditional procedures
      to almond residues that nowadays are mainly addressed to livestock feed and
      energy production. In this sense; data available on the physicochemical and
      phytochemical composition of almond meat and its related residues suggest
      promising applications; and allow one to envisage new uses as functional
      ingredients towards value-added foods and feeds; as well as a source of bioactive
      phytochemicals to be included in cosmetic formulations. This objective has
      prompted investigators working in the field to evaluate their functional
      properties and biological activity. This approach has provided interesting
      information concerning the capacity of polyphenolic extracts of almond by
      products to prevent degenerative diseases linked to oxidative stress and
      inflammation in human tissues and cells; in the frame of diverse
      pathophysiological situations. Hence; this review deals with gathering data
      available in the scientific literature on the phytochemical composition and
      bioactivity of almond by-products as well as on their bioactivity so as to
      promote their functional application.

PMID- 29053617
TI  - Synthesis of Siloxyalumoxanes and Alumosiloxanes Based on Organosilicon Diols.
AB  - We have drawn a few interesting conclusions while studying reaction products of
      Ph2Si(OH)2 with Al(iBu)3 and tetraisobutylalumoxane. In the first place, this is
      the production (at a Ph2Si(OH)2 and Al(iBu)3 equimolar ratio) of an oligomer
      siloxyalumoxane structure with alternating four- and six-member rings. In
      addition, it shows isobutyl and phenyl group migration between aluminum and
      silicon due to the formation of an intramolecular four-member cyclic complex
      [Ph2(OH)SiO]Al(iBu)2 -> [(iBu)Ph(OH)SiO]Al(iBu)Ph. Ph2Si(OH)2 interaction with
      Al(iBu)3 not only starts from intramolecular complex production, but the chain is
      terminated for the same reason, which in the case of the Ph2Si(OH)2 reaction with
      tetraisobutylalumoxane results in failure of to obtain high-polymer
      siloxyalumoxane compounds. When Al(iBu)3 interacts with alpha- and gamma-diols,
      no oligomer compounds are produced. In the Al(iBu)3 reaction with alpha, gamma
      diols are created in monomer compounds that are likely to have a cyclic
      structure. Notably, when Al(iBu)3 interacts with only alpha-diol, a double excess
      of Al(iBu)3 allows for full replacement of hydrogen in the alpha-diol hydroxyl
      groups by aluminum alkyl residue with 1,3-bis(diisobutylalumoxymethyl)-1,1,3,3
      tetramethyldisiloxane production. At an equimolar ratio of initial reagents, the
      second isobutyl radical at Al does not interact with the second hydroxyl group of
      alpha-diol, apparently due to the steric hindrance, and 1
      (diisobutylalumoxymethyl)-3-(hydroxymethyl)-1,1,3,3-tetramethyl-disiloxane is
      produced. Al(iBu)3 reactions with gamma-diol also result in monomer compounds,
      but the presence of a chain consisting of three CH2-groups between Si and the
      hydroxyl group facilitates interaction between the second hydroxyl group of gamma
      diol and the second isobutyl radical Al(iBu)3. Tetraisobutylalumoxane reactions
      with alpha- and gamma-diols result in oligomer compounds.

PMID- 29053619
TI  - Cellulase-Assisted Extraction of Polysaccharides from White Hyacinth Bean:
      Characterization of Antioxidant Activity and Promotion for Probiotics
      Proliferation.
AB  - Food-derived polysaccharides have advantages over synthetical compounds and have
      attracted interest globally for decades. In this study, we optimized the
      cellulase-assisted extraction of polysaccharides from white hyacinth bean (PWBs)
      with the aid of response surface methodology (RSM). The optimum extraction
      parameters were a pH of 7.79, a cellulase of 2.73%, and a ratio of water to
      material of 61.39, producing a high polysaccharide yield (3.32 +/- 0.03)%. The
      scavenging ability of PWBs varied on three radicals (hydroxyl > 2,2-diphenyl-1
      picrylhydrazyl (DPPH) > superoxide). Furthermore, PWBs contributed to the
      proliferation of three probiotic bacteria (Lactobacillus acidophilus LA5,
      Bifidobacterium bifidum BB01, and Lactobacillus bulgaricus LB6). These
      investigations of PWBs provide a novel bioresource for the exploitation of
      antioxidant and probiotic bacterial proliferation.

PMID- 29053618
TI  - The Application of Ultra-High-Performance Liquid Chromatography Coupled with a
      LTQ-Orbitrap Mass Technique to Reveal the Dynamic Accumulation of Secondary
      Metabolites in Licorice under ABA Stress.
AB  - The traditional medicine licorice is the most widely consumed herbal product in
      the world. Although much research work on studying the changes in the active
      compounds of licorice has been reported, there are still many areas, such as the
      dynamic accumulation of secondary metabolites in licorice, that need to be
      further studied. In this study, the secondary metabolites from licorice under two
      different methods of stress were investigated by ultra-high-performance liquid
      chromatography coupled with hybrid linear ion trap-Orbitrap mass spectrometry
      (UHPLC-LTQ-Orbitrap-MS). A complex continuous coordination of flavonoids and
      triterpenoids in a network was modulated by different methods of stress during
      growth. The results showed that a total of 51 secondary metabolites were
      identified in licorice under ABA stress. The partial least squares-discriminate
      analysis (PLS-DA) revealed the distinction of obvious compounds among stress
      specific districts relative to ABA stress. The targeted results showed that there
      were significant differences in the accumulation patterns of the deeply targeted
      41 flavonoids and 10 triterpenoids compounds by PCA and PLS-DA analyses. To
      survey the effects of flavonoid and triterpenoid metabolism under ABA stress, we
      inspected the stress-specific metabolic changes. Our study testified that the
      majority of flavonoids and triterpenoids were elevated in licorice under ABA
      stress, while the signature metabolite affecting the dynamic accumulation of
      secondary metabolites was detected. Taken together, our results suggest that ABA
      specific metabolite profiling dynamically changed in terms of the biosynthesis of
      flavonoids and triterpenoids, which may offer new trains of thought on the
      regular pattern of dynamic accumulation of secondary metabolites in licorice at
      the metabolite level. Our results also provide a reference for clinical
      applications and directional planting and licorice breeding.

PMID- 29053620
TI  - Self-Nanoemulsifying Drug Delivery Systems Containing Plantago lanceolata-An
      Assessment of Their Antioxidant and Antiinflammatory Effects.
AB  - The most important components of Plantago lanceolata L. leaves are catalpol,
      aucubin, and acteoside (=verbascoside). These bioactive compounds possess
      different pharmacological effects: anti-inflammatory, antioxidant,
      antineoplastic, and hepatoprotective. The aim of this study was to protect
      Plantago lanceolata extract from hydrolysis and to improve its antioxidant effect
      using self-nano-emulsifying drug delivery systems (SNEDDS). Eight SNEDDS
      compositions were prepared, and their physical properties, in vitro cytotoxicity,
      and in vivo AST/ALT values were investigated. MTT cell viability assay was
      performed on Caco-2 cells. The well-diluted samples (200 to 1000-fold dilutions)
      proved to be non-cytotoxic. The acute administration of PL-SNEDDS compositions
      resulted in minor changes in hepatic markers (AST, ALT), except for compositions
      4 and 8 due to their high Transcutol contents (80%). The non-toxic compositions
      showed a significant increase in free radical scavenger activity measured by the
      DPPH test compared to the blank SNEDDS. An indirect dissolution test was
      performed, based on the result of the DPPH antioxidant assay; the dissolution
      profiles of Plantago lancolata extract were statistically different from each
      SNEDDS. The anti-inflammatory effect of PL-SNEDDS compositions was confirmed by
      the ear inflammation test. For the complete examination period, all compositions
      decreased ear edema as compared to the positive (untreated) control. It can be
      concluded that PL-SNEDDS compositions could be used to deliver active natural
      compounds in a stable, efficient, and safe manner.

PMID- 29053621
TI  - Isoproterenol Increases RANKL Expression in a ATF4/NFATc1-Dependent Manner in
      Mouse Osteoblastic Cells.
AB  - Sympathetic nervous system stimulation-induced beta-adrenergic signal
      transduction is known to induce bone loss and increase of osteoclast activity.
      Although isoproterenol, a nonspecific beta-adrenergic receptor agonist, has been
      shown to increase receptor activator of NF-kappaB ligand (RANKL), the details of
      the regulatory mechanisms remain unclear. In the present study, we investigated
      the role of the nuclear factor of activated T-cells (NFAT) in isoproterenol
      induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells.
      Isoproterenol increased nuclear factor of activated T-cells cytoplasmic 1
      (NFATc1) and RANKL expressions at both mRNA and protein levels and increased NFAT
      reporter activity. NFATc1 knockdown blocked isoproterenol-mediated RANKL
      expression. Isoproterenol also promoted cAMP response element-binding protein 1
      (CREB1) and activating transcription factor 4 (ATF4) phosphorylation.
      Isoproterenol-mediated transcriptional activation of NFAT was blocked by protein
      kinase A (PKA) inhibitor H89. Isoproterenol-induced CREB1, ATF4, NFATc1, and
      RANKL expressions were suppressed by H89. Mutations in cAMP response element-like
      or NFAT-binding element suppressed isoproterenol-induced RANKL promoter activity.
      Chromatin immunoprecipitation analysis demonstrated that isoproterenol increased
      NFAT-binding and ATF4-binding activities on the mouse RANKL promoter, but did not
      increase CREB1-binding activity. Association of NFATc1 and ATF4 was not observed
      in a co-immunoprecipitation study. ATF4 knockdown suppressed isoproterenol
      induced NFAT binding to the RANKL promoter, whereas NFATc1 knockdown did not
      suppress isoproterenol-induced ATF4 binding to the RANKL promoter. ATF4 knockdown
      suppressed isoproterenol-induced expressions of NFATc1 and RANKL. These results
      suggest that isoproterenol increases RANKL expression in an ATF4/NFATc1-dependent
      manner.

PMID- 29053622
TI  - Sleep Disturbances in Newborns.
AB  - The purpose of this review is to serve as an introduction to understanding sleep
      in the fetus, the preterm neonate and the term neonate. Sleep appears to have
      numerous important roles, particularly in the consolidation of new information.
      The sleep cycle changes over time, neonates spend the most time in active sleep
      and have a progressive shortening of active sleep and lengthening of quiet sleep.
      Additionally, the sleep cycle is disrupted by many things including disease state
      and environment, and the amplitude integrated EEG can be a useful tool in
      evaluating sleep, and sleep disturbances, in neonates. Finally, there are
      protective factors for infant sleep that are still being studied.

PMID- 29053623
TI  - Transfer-Efficient Face Routing Using the Planar Graphs of Neighbors in High
      Density WSNs.
AB  - Face routing has been adopted in wireless sensor networks (WSNs) where
      topological changes occur frequently or maintaining full network information is
      difficult. For message forwarding in networks, a planar graph is used to prevent
      looping, and because long edges are removed by planarization and the resulting
      planar graph is composed of short edges, and messages are forwarded along
      multiple nodes connected by them even though they can be forwarded directly. To
      solve this, face routing using information on all nodes within 2-hop range was
      adopted to forward messages directly to the farthest node within radio range.
      However, as the density of the nodes increases, network performance plunges
      because message transfer nodes receive and process increased node information. To
      deal with this problem, we propose a new face routing using the planar graphs of
      neighboring nodes to improve transfer efficiency. It forwards a message directly
      to the farthest neighbor and reduces loads and processing time by distributing
      network graph construction and planarization to the neighbors. It also decreases
      the amount of location information to be transmitted by sending information on
      the planar graph nodes rather than on all neighboring nodes. Simulation results
      show that it significantly improves transfer efficiency.

PMID- 29053624
TI  - Fabrication of Ordered SnO2 Nanostructures with Enhanced Humidity Sensing
      Performance.
AB  - Ordered SnO2 nanostructures were prepared as humidity sensors by nanosphere
      lithography with the magnetron sputtering technique. The X-ray diffraction
      patterns of SnO2 nanostructures show that all intense diffraction peaks
      correspond to the crystallographic planes of SnO2. The Atomic Force Microscope
      (AFM) mage shows that these SnO2 nanostructures exhibited a classic honeycomb
      structure. The resistance of this sensor was measured to show that the resistance
      of the sensor decreases with an increase from lower relative humidity (RH) to
      higher RH. Additionally, the longest response/recovery time was 32 s/42 s for 11
      96% RH. The hysteresis for the SnO2 nanostructure sensor was <5%.

PMID- 29053625
TI  - Traditional Uses, Origins, Chemistry and Pharmacology of Bombyx batryticatus: A
      Review.
AB  - Bombyx batryticatus (B. batryticatus), a well-known traditional animal Chinese
      medicine, has been commonly used in China for thousands of years. The present
      paper reviewed advances in traditional uses, origin, chemical constituents,
      pharmacology and toxicity studies of B. batryticatus. The aim of the paper is to
      provide more comprehensive references for modern B. batryticatus study and
      application. In Traditional Chinese Medicine (TCM) culture, drugs containing B.
      batryticatus have been used to treat convulsions, headaches, skin prurigo,
      scrofula, tonsillitis and fever. Many studies indicate B. batryticatus contains
      various compounds, including protein and peptides, fatty acids, flavonoids,
      nucleosides, steroids, coumarin, polysaccharide and others. Numerous
      investigations also have shown that extracts and compounds from B. batryticatus
      exert a wide spectrum of pharmacological effects both in vivo and in vitro,
      including effects on the nervous system, anticoagulant effects, antitumor
      effects, antibacterial and antifungal effects, antioxidant effects, hypoglycemic
      effects, as well as other effects. However, further studies should be undertaken
      to investigate bioactive compounds (especially proteins and peptides), toxic
      constituents, using forms and the quality evaluation and control of B.
      batryticatus. Furthermore, it will be interesting to study the mechanism of
      biological activities and structure-function relationships of bioactive
      constituents in B. batryticatus.

PMID- 29053627
TI  - Silicon Nanocrystals with pH-Sensitive Tunable Light Emission from Violet to Blue
      Green.
AB  - We fabricated a silicon nanocrystal (NC) suspension with visible, continuous,
      tunable light emission with pH sensitivity from violet to blue-green.
      Transmission electron microscopy (TEM) images and X-ray diffraction (XRD) pattern
      analysis exhibit the highly crystalline nanoparticles of silicon.
      Photoluminescence (PL) spectra and photoluminescence excitation (PLE) spectra at
      different pH values, such as 1, 3, 5, 7, 9, and 11, reveal the origins of light
      emission from the silicon NC suspension, which includes both the quantum
      confinement effect and surface bonding. The quantum confinement effect dominates
      the PL origins of silicon NCs, especially determining the tunability and the
      emission range of PL, while the surface bonding regulates the maximum peak
      center, full width at half maximum (FWHM), and offsets of PL peaks in response to
      the changing pH value. The peak fitting of PLE curves reveals one of the divided
      PLE peaks shifts towards a shorter wavelength when the pH value increases, which
      implies correspondence with the surface bonding between silicon NCs and hydrogen
      atoms or hydroxyl groups. The consequent detailed analysis of the PL spectra
      indicates that the surface bonding results in the transforming of the PL curves
      towards longer wavelengths with the increasing pH values, which is defined as the
      pH sensitivity of PL. These results suggest that the present silicon NCs with pH
      sensitive tunable light emission could find promising potential applications as
      optical sources, bio-sensors, etc.

PMID- 29053626
TI  - A Systematic Review of Computational Drug Discovery, Development, and Repurposing
      for Ebola Virus Disease Treatment.
AB  - Ebola virus disease (EVD) is a deadly global public health threat, with no
      currently approved treatments. Traditional drug discovery and development is too
      expensive and inefficient to react quickly to the threat. We review published
      research studies that utilize computational approaches to find or develop drugs
      that target the Ebola virus and synthesize its results. A variety of hypothesized
      and/or novel treatments are reported to have potential anti-Ebola activity.
      Approaches that utilize multi-targeting/polypharmacology have the most promise in
      treating EVD.

PMID- 29053629
TI  - An Improved Indoor Positioning System Using RGB-D Cameras and Wireless Networks
      for Use in Complex Environments.
AB  - This work presents an Indoor Positioning System to estimate the location of
      people navigating in complex indoor environments. The developed technique
      combines WiFi Positioning Systems and depth maps, delivering promising results in
      complex inhabited environments, consisting of various connected rooms, where
      people are freely moving. This is a non-intrusive system in which personal
      information about subjects is not needed and, although RGB-D cameras are
      installed in the sensing area, users are only required to carry their smart
      phones. In this article, the methods developed to combine the above-mentioned
      technologies and the experiments performed to test the system are detailed. The
      obtained results show a significant improvement in terms of accuracy and
      performance with respect to previous WiFi-based solutions as well as an extension
      in the range of operation.

PMID- 29053628
TI  - Antioxidant Defence, Oxidative Stress and Oxidative Damage in Saliva, Plasma and
      Erythrocytes of Dementia Patients. Can Salivary AGE be a Marker of Dementia?
AB  - Oxidative stress plays a crucial role in dementia pathogenesis; however, its
      impact on salivary secretion and salivary qualities is still unknown. This study
      included 80 patients with moderate dementia and 80 healthy age- and sex-matched
      individuals. Salivary flow, antioxidants (salivary peroxidase, catalase,
      superoxide dismutase, uric acid and total antioxidant capacity), and oxidative
      damage products (advanced oxidation protein products, advanced glycation end
      products (AGE), 8-isoprostanes, 8-hydroxy-2'-deoxyguanosine and total oxidant
      status) were estimated in non-stimulated and stimulated saliva, as well as in
      plasma and erythrocytes. We show that in dementia patients the
      concentration/activity of major salivary antioxidants changes, and the level of
      oxidative damage to DNA, proteins and lipids is increased compared to healthy
      controls. Non-stimulated and stimulated salivary secretions were significantly
      reduced in dementia patients. The deterioration in mini mental state examination
      (MMSE) score correlated with salivary AGE levels, which when considered with
      receiver operating characteristic (ROC) analysis, suggests their potential role
      in the non-invasive diagnosis of dementia. In conclusion, dementia is associated
      with disturbed salivary redox homeostasis and impaired secretory function of the
      salivary glands. Salivary AGE may be useful in the diagnosis of dementia.

PMID- 29053630
TI  - Rapid Classification and Identification of Chemical Components of Schisandra
      Chinensis by UPLC-Q-TOF/MS Combined with Data Post-Processing.
AB  - Schisandra chinensis (known in Chinese as WuWeiZi, WWZ) has observable effects
      such as astringing the lung to stop coughs, arresting sweating, preserving semen
      and preventing diarrhea. The major components of WWZ include lignans,
      triterpenoids, organic acids and fatty acids. In this paper, a reliable method
      for the rapid identification of multiple components in WWZ by their
      characteristic fragments and neutral losses using UPLC-Q-TOF/MS technology was
      developed. After review of the literature and some reference experiments, the
      fragmentation pattern of several compounds were studied and summarized. Then,
      according to the corresponding characteristic fragments coupled with neutral
      losses in the positive or negative ion mode produced by different types of
      substances a rapid identification of target compounds was achieved. Finally, a
      total of 30 constituents of WWZ were successfully identified, including 15
      lignans, nine triterpenoids, three organic acids and three fatty acids. The
      method established in this study not only provides a comprehensive analysis of
      the chemical ingredients of WWZ, providing a basis for further phytochemical
      studies on WWZ but also provides a more efficient way to solve the problem of
      identification of complex chemical constituents in traditional Chinese medicines.

PMID- 29053631
TI  - Experience of Japan in Achieving a Total Ban on Asbestos.
AB  - This paper aims to examine the process through which a total ban on asbestos was
      achieved in Japan. We reconstructed the process, analyzed the roles of involved
      parties/events, and drew lessons from the Japanese experience of achieving the
      ban. In Japan, a bill to phase out asbestos was proposed in 1992 but rejected
      without deliberation. Wide support for such a ban subsequently grew, however,
      largely due to the actions of trade unions and civil societies in establishing a
      coalition, raising awareness, organizing asbestos victims and their families, and
      propagating information on international developments. A governmental decision
      towards a ban was made in 2002 based on several national and international
      factors. A huge asbestos scandal in 2005 preponed the achievement of a total ban
      and led to the establishment of comprehensive measures to tackle asbestos issues.
      However, challenges remain for the elimination of asbestos-related diseases.

PMID- 29053632
TI  - Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against
      Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and
      Inflammation in Mice.
AB  - This study was aimed to investigate the chemical composition, antioxidant
      activities and hepatoprotective effect of flavonoids from Ziziphus jujuba cv.
      Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance
      liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS),
      and antioxidant properties were investigated by biological assays in vitro. The
      hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated
      BALB/c mice. Results indicate that ZJF displayed significant antioxidant
      capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
      phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration,
      while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced.
      Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related
      factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of
      NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF
      attenuated APAP-induced inflammatory mediator production, such as nitric oxide
      (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and
      interleukin-1beta (IL-1beta). Expression of p65 showed that ZJF dampened nuclear
      factor-kappaB (NF-kappaB) activation. The results strongly indicate that the
      hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its
      induction of antioxidant defense via activation of Nrf2 and reduction of
      inflammation via inhibition of NF-kappaB.

PMID- 29053633
TI  - Diversity and Phylogenetic Analyses of Bacterial Symbionts in Three Whitefly
      Species from Southeast Europe.
AB  - Bemisia tabaci (Gennadius), Trialeurodes vaporariorum (Westwood), and Siphoninus
      phillyreae (Haliday) are whitefly species that harm agricultural crops in many
      regions of the world. These insects live in close association with bacterial
      symbionts that affect host fitness and adaptation to the environment. In the
      current study, we surveyed the infection of whitefly populations in Southeast
      Europe by various bacterial symbionts and performed phylogenetic analyses on the
      different symbionts detected. Arsenophonus and Hamiltonella were the most
      prevalent symbionts in all three whitefly species. Rickettsia was found to infect
      mainly B. tabaci, while Wolbachia mainly infected both B. tabaci and S.
      phillyreae. Furthermore, Cardinium was rarely found in the investigated whitefly
      populations, while Fritschea was never found in any of the whitefly species
      tested. Phylogenetic analyses revealed a diversity of several symbionts (e.g.,
      Hamiltonella, Arsenophonus, Rickettsia), which appeared in several clades.
      Reproductively isolated B. tabaci and T. vaporariorum shared the same (or highly
      similar) Hamiltonella and Arsenophonus, while these symbionts were distinctive in
      S. phillyreae. Interestingly, Arsenophonus from S. phillyreae did not cluster
      with any of the reported sequences, which could indicate the presence of
      Arsenophonus, not previously associated with whiteflies. In this study, symbionts
      (Wolbachia, Rickettsia, and Cardinium) known to infect a wide range of insects
      each clustered in the same clades independently of the whitefly species. These
      results indicate horizontal transmission of bacterial symbionts between
      reproductively isolated whitefly species, a mechanism that can establish new
      infections that did not previously exist in whiteflies.

PMID- 29053634
TI  - Petroleum Hydrocarbon Profiles of Water and Sediment of Algoa Bay, Eastern Cape,
      South Africa.
AB  - Petroleum hydrocarbon profiles of water and sediment samples of Algoa Bay in the
      Eastern Cape Province of South Africa were assessed using standard analytical
      procedures. Water (from surface and bottom levels) and sediment samples were
      collected from five locations in the bay from February to June 2016. Extraction
      of the petroleum hydrocarbons from the water and sediment samples collected was
      achieved using liquid-liquid and Soxhlet extraction techniques, respectively,
      followed by column clean up. Target compounds were analytically determined with
      gas chromatography-flame ionization detector (GC-FID) and quantified by
      integrating the areas of both the resolved and unresolved components.
      Physicochemical properties of the water samples were also determined on site
      using a SeaBird 19plusV2 CTD SBE 55 device. Estimated limit of detection, limit
      of quantitation and relative standard deviation for the 35 n-alkane standards
      ranged from 0.06 to 0.13 MUg/L, 0.30 to 0.69 MUg/L and 3.61 to 8.32%,
      respectively. Results showed that total petroleum hydrocarbon (TPH) varied from
      45.07 to 307 MUg/L in the water and 0.72 to 27.03 mg/kg in the sediments. The
      mean concentrations of TPH in both the water and sediment samples from Algoa Bay
      revealed a slight level of pollution. The diagnostic indices used showed that the
      hydrocarbons in the area were from both biogenic and anthropogenic sources.
      Hence, there is need for adequate regulation and control of all activities
      contributing to the levels of petroleum hydrocarbon in the marine environment for
      the safety of human, aquatic and wild lives in the area.

PMID- 29053635
TI  - Differential Interaction of Antimicrobial Peptides with Lipid Structures Studied
      by Coarse-Grained Molecular Dynamics Simulations.
AB  - In this work; we investigated the differential interaction of amphiphilic
      antimicrobial peptides with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
      (POPC) lipid structures by means of extensive molecular dynamics simulations. By
      using a coarse-grained (CG) model within the MARTINI force field; we simulated
      the peptide-lipid system from three different initial configurations: (a)
      peptides in water in the presence of a pre-equilibrated lipid bilayer; (b)
      peptides inside the hydrophobic core of the membrane; and (c) random
      configurations that allow self-assembled molecular structures. This last approach
      allowed us to sample the structural space of the systems and consider cooperative
      effects. The peptides used in our simulations are aurein 1.2 and maculatin 1.1;
      two well-known antimicrobial peptides from the Australian tree frogs; and
      molecules that present different membrane-perturbing behaviors. Our results
      showed differential behaviors for each type of peptide seen in a different
      organization that could guide a molecular interpretation of the experimental
      data. While both peptides are capable of forming membrane aggregates; the aurein
      1.2 ones have a pore-like structure and exhibit a higher level of organization
      than those conformed by maculatin 1.1. Furthermore; maculatin 1.1 has a strong
      tendency to form clusters and induce curvature at low peptide-lipid ratios. The
      exploration of the possible lipid-peptide structures; as the one carried out
      here; could be a good tool for recognizing specific configurations that should be
      further studied with more sophisticated methodologies.

PMID- 29053639
TI  - Effects of Silicon Amendment on Soilborne and Fruit Diseases of Avocado.
AB  - The effects of silicon (Si) amendment have been studied in several plant/pathogen
      interactions; however, studies in horticultural tree crops are limited. Effects
      of amendment with soluble potassium silicate (AgSil(r)32, approximately 30%
      available Si), or milled cement building board by-products (Mineral Mulch (MM) or
      Mineral Dust (MD), containing 5% available Si) were investigated in field and
      greenhouse trials with avocado. Orchard soil drench applications with potassium
      silicate improved yield and quality of fruit, but visual health of trees
      declining from Phytophthora root rot (PRR) was not affected. Orchard spray or
      trunk injection applications with potassium silicate were ineffective. Amendment
      of potting mix with MM and MD reduced root necrosis of avocado seedlings after
      inoculation with Calonectria ilicicola, an aggressive soilborne pathogen causing
      black root rot. Application of MM to mature orchard trees declining with PRR had
      a beneficial effect on visual tree health, and Si accumulation in leaves and
      fruit peel, after only 10 months. Products that deliver available Si consistently
      for uptake are likely to be most successful in perennial tree crops.

PMID- 29053640
TI  - Enhancing Resources at the Workplace with Health-Promoting Leadership.
AB  - Leaders engaging in health-promoting leadership can influence their employees'
      health directly by showing health awareness or indirectly by changing working
      conditions. With health-promoting leadership, leaders are able to support a
      healthy working environment by providing resource-oriented working conditions for
      their employees to support their health. Changing working conditions in a health
      supportive way can prevent possible negative consequences from critical working
      conditions (e.g., burnout risk). The present study examined the relationship
      between health-promoting leadership and the employees' resources, stress and
      burnout. To analyze our proposed model, structural equation modelling was
      conducted in two samples. The resulting model from the first sample of 228
      Austrian workers was cross-validated and could be verified with the second sample
      (N = 263 Austrian workers). The results supported a model in which health
      promoting leadership has a strong direct effect on the employees' resources and
      an indirect effect on stress and burnout, which was mediated by resources. The
      results indicate that health-promoting leadership describes the leaders'
      capability and dedication creating the right working conditions for their
      employees by increasing the employees' resources at the workplace. This in turn
      minimizes the risk of experiencing burnout.

PMID- 29053636
TI  - Neural and Molecular Mechanisms Involved in Controlling the Quality of Feeding
      Behavior: Diet Selection and Feeding Patterns.
AB  - We are what we eat. There are three aspects of feeding: what, when, and how much.
      These aspects represent the quantity (how much) and quality (what and when) of
      feeding. The quantitative aspect of feeding has been studied extensively, because
      weight is primarily determined by the balance between caloric intake and
      expenditure. In contrast, less is known about the mechanisms that regulate the
      qualitative aspects of feeding, although they also significantly impact the
      control of weight and health. However, two aspects of feeding quality relevant to
      weight loss and weight regain are discussed in this review: macronutrient-based
      diet selection (what) and feeding pattern (when). This review covers the
      importance of these two factors in controlling weight and health, and the central
      mechanisms that regulate them. The relatively limited and fragmented knowledge on
      these topics indicates that we lack an integrated understanding of the
      qualitative aspects of feeding behavior. To promote better understanding of
      weight control, research efforts must focus more on the mechanisms that control
      the quality and quantity of feeding behavior. This understanding will contribute
      to improving dietary interventions for achieving weight control and for
      preventing weight regain following weight loss.

PMID- 29053637
TI  - Progress in Genetic Studies of Tourette's Syndrome.
AB  - Tourette's Syndrome (TS) is a complex disorder characterized by repetitive,
      sudden, and involuntary movements or vocalizations, called tics. Tics usually
      appear in childhood, and their severity varies over time. In addition to frequent
      tics, people with TS are at risk for associated problems including attention
      deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD),
      anxiety, depression, and problems with sleep. TS occurs in most populations and
      ethnic groups worldwide, and it is more common in males than in females. Previous
      family and twin studies have shown that the majority of cases of TS are
      inherited. TS was previously thought to have an autosomal dominant pattern of
      inheritance. However, several decades of research have shown that this is
      unlikely the case. Instead TS most likely results from a variety of genetic and
      environmental factors, not changes in a single gene. In the past decade, there
      has been a rapid development of innovative genetic technologies and
      methodologies, as well as significant progresses in genetic studies of
      psychiatric disorders. In this review, we will briefly summarize previous genetic
      epidemiological studies of TS and related disorders. We will also review previous
      genetic studies based on genome-wide linkage analyses and candidate gene
      association studies to comment on problems of previous methodological and
      strategic issues. Our main purpose for this review will be to summarize the new
      genetic discoveries of TS based on novel genetic methods and strategies, such as
      genome-wide association studies (GWASs), whole exome sequencing (WES) and whole
      genome sequencing (WGS). We will also compare the new genetic discoveries of TS
      with other major psychiatric disorders in order to understand the current status
      of TS genetics and its relationship with other psychiatric disorders.

PMID- 29053638
TI  - Neuroprotective Surgical Strategies in Parkinson's Disease: Role of Preclinical
      Data.
AB  - Although there have been many pharmacological agents considered to be
      neuroprotective therapy in Parkinson's disease (PD) patients, neurosurgical
      approaches aimed to neuroprotect or restore the degenerative nigrostriatal system
      have rarely been the focus of in depth reviews. Here, we explore the
      neuroprotective strategies involving invasive surgical approaches (NSI) using
      neurotoxic models 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6
      hydroxydopamine (6-OHDA), which have led to clinical trials. We focus on several
      NSI approaches, namely deep brain stimulation of the subthalamic nucleus, glial
      neurotrophic derived factor (GDNF) administration and cell grafting methods.
      Although most of these interventions have produced positive results in
      preclinical animal models, either from behavioral or histological studies, they
      have generally failed to pass randomized clinical trials to validate each
      approach. We argue that NSI are promising approaches for neurorestoration in PD,
      but preclinical studies should be planned carefully in order not only to detect
      benefits but also to detect potential adverse effects. Further, clinical trials
      should be designed to be able to detect and disentangle neuroprotection from
      symptomatic effects. In summary, our review study evaluates the pertinence of
      preclinical models to study NSI for PD and how this affects their efficacy when
      translated into clinical trials.

PMID- 29053641
TI  - Wear and Tear of Tyres: A Stealthy Source of Microplastics in the Environment.
AB  - Wear and tear from tyres significantly contributes to the flow of (micro
      )plastics into the environment. This paper compiles the fragmented knowledge on
      tyre wear and tear characteristics, amounts of particles emitted, pathways in the
      environment, and the possible effects on humans. The estimated per capita
      emission ranges from 0.23 to 4.7 kg/year, with a global average of 0.81 kg/year.
      The emissions from car tyres (100%) are substantially higher than those of other
      sources of microplastics, e.g., airplane tyres (2%), artificial turf (12-50%),
      brake wear (8%) and road markings (5%). Emissions and pathways depend on local
      factors like road type or sewage systems. The relative contribution of tyre wear
      and tear to the total global amount of plastics ending up in our oceans is
      estimated to be 5-10%. In air, 3-7% of the particulate matter (PM2.5) is
      estimated to consist of tyre wear and tear, indicating that it may contribute to
      the global health burden of air pollution which has been projected by the World
      Health Organization (WHO) at 3 million deaths in 2012. The wear and tear also
      enters our food chain, but further research is needed to assess human health
      risks. It is concluded here that tyre wear and tear is a stealthy source of
      microplastics in our environment, which can only be addressed effectively if
      awareness increases, knowledge gaps on quantities and effects are being closed,
      and creative technical solutions are being sought. This requires a global effort
      from all stakeholders; consumers, regulators, industry and researchers alike.

PMID- 29053642
TI  - Allelic Expression Imbalance in the Human Retinal Transcriptome and Potential
      Impact on Inherited Retinal Diseases.
AB  - Inherited retinal diseases (IRDs) are often associated with variable clinical
      expressivity (VE) and incomplete penetrance (IP). Underlying mechanisms may
      include environmental, epigenetic, and genetic factors. Cis-acting expression
      quantitative trait loci (cis-eQTLs) can be implicated in the regulation of genes
      by favoring or hampering the expression of one allele over the other. Thus, the
      presence of such loci elicits allelic expression imbalance (AEI) that can be
      traced by massive parallel sequencing techniques. In this study, we performed an
      AEI analysis on RNA-sequencing (RNA-seq) data, from 52 healthy retina donors,
      that identified 194 imbalanced single nucleotide polymorphisms(SNPs) in 67 IRD
      genes. Focusing on SNPs displaying AEI at a frequency higher than 10%, we found
      evidence of AEI in several IRD genes regularly associated with IP and VE (BEST1,
      RP1, PROM1, and PRPH2). Based on these SNPs commonly undergoing AEI, we performed
      pyrosequencing in an independent sample set of 17 healthy retina donors in order
      to confirm our findings. Indeed, we were able to validate CDHR1, BEST1, and PROM1
      to be subjected to cis-acting regulation. With this work, we aim to shed light on
      differentially expressed alleles in the human retina transcriptome that, in the
      context of autosomal dominant IRD cases, could help to explain IP or VE.

PMID- 29053643
TI  - Genome-Wide Identification and Analysis of MAPK and MAPKK Gene Families in Bread
      Wheat (Triticum aestivum L.).
AB  - The mitogen-activated protein kinase (MAPK) cascade is a universal signal
      transduction module that plays a vital role in regulating growth and development,
      as well as environmental stress responses in plants. Wheat is one of the most
      important crops worldwide. Although the MAPK kinase kinase (MAP3K) family in
      wheat has been investigated, the MAPK and MAPK kinase (MAP2K) gene families
      remain unknown at present. Here, 54 MAPK and 18 MAPKK genes were identified in
      wheat using recent genomic information. Phylogenetic analysis of Triticum
      aestivum L. MAPKs and MAPKKs (TaMAPKs and TaMAPKKs) together with homologous
      genes from other species classified them into four groups, and the clustering was
      consistent with the genomic exon/intron structures. Conserved motif analysis
      found that MAPK proteins contained a typical TXY phosphorylation site and MAPKK
      proteins contained an S/T-X5-S/T motif. RNA-seq data mapping analysis showed that
      MAPK and MAPKK genes in group IV had tissue-specific expression profiles, whereas
      each group I member showed relatively high expression in all organs. Expression
      patterns of TaMAPK and TaMAPKK genes under stress conditions were also
      investigated and stress-responsive candidates were identified. Co-expression
      network analysis identified 11 TaMAPK genes and 6 TaMAPKK genes involved in the
      interaction network pathway. Overall, this study provided useful information for
      evolutionary and functional surveys of MAPK and MAPKK gene families in wheat and
      beyond.

PMID- 29053644
TI  - Dental approach for Apert syndrome in children: a systematic review.
AB  - BACKGROUND: Apert Syndrome (AS), or type I acrocephalosyndactyly, is a rare,
      congenital craniosynostosis condition resulting from missense mutations in the
      gene encoding fibroblast growth factor receptor 2. It is characterized by three
      specific clinical features: brachycephalic skull; midface hypoplasia, and limb
      abnormalities (syndactyly of hands and feet). The disorder exhibits variable
      presentations in bones, brain, skin, internal organs, and in the
      oral/maxillofacial region. The aim of the present paper was to show the main
      results from a systematic review of AS. MATERIAL AND METHODS: A search of the
      literature was performed from April to June 2016 in five electronic databases.
      Clinical interventional or observational studies, reviews, and case reports were
      included. The present systematic review was carried out strictly following PRISMA
      and Cochrane Collaboration criteria. RESULTS: A total of 129 potential references
      were identified. After reviewing titles and abstracts, 77 of these did not meet
      the desired criteria and were discarded. The full text of the remaining 52
      manuscripts was critically screened. Finally, 35 relevant papers were identified
      for inclusion in the present systematic review and classified according to topic
      type. CONCLUSIONS: According to the information gathered, dentistry practitioners
      must be able to supply an early diagnosis through the recognition of AS clinical
      features and provide correct oral management. Additionally, they should be
      integrated in a multidisciplinary medical care team in order to improve the
      quality of life of the affected patients.

PMID- 29053645
TI  - Comparison of peri-implant bone loss between conventional drilling with
      irrigation versus low-speed drilling without irrigation.
AB  - BACKGROUND: To compare the technique of high speed drilling with irrigation and
      low speed drilling without irrigation in order to evaluate the success rate and
      peri-implant bone loss at 12 months of follow-up. MATERIAL AND METHODS: A
      randomized, controlled, parallel-group clinical trial was carried out in patients
      requiring dental implants to rehabilitate their unitary edentulism. Patients were
      recruited from the Oral Surgery Unit of the University of Valencia (Spain)
      between September 2014 and August 2015. Patients who met the inclusion criteria
      were randomized to two groups: group A (high-speed drilling with irrigation) and
      group B (low-speed drilling without irrigation). The success rate and peri
      implant bone loss were recorded at 12 months of follow-up. RESULTS: Twenty-five
      patients (9 men and 16 women) with 30 implants were enrolled in the study: 15
      implants in group A and 15 implants in group B. The mean bone loss of the
      implants in group A and group B was 0.83 +/- 0.73 mm and 0.62 +/- 0.70 mm,
      respectively (p> 0.05). In the maxilla, the bone loss was 1.04 +/- 0.63 mm in
      group A and 0.71 +/- 0.36 mm in group B (p> 0.05), while bone loss in the
      mandible was 0.59 +/- 0.80 mm in group A and 0.69 +/- 0.77 mm in group B (p>
      0.05). The implant success rate at 12 months was 93.3% in group A and 100% in
      group B. CONCLUSIONS: Within the limitations of the study, the low-speed drilling
      technique presented peri-implant bone loss outcomes similar to those of the
      conventional drilling technique at 12 months of follow-up.

PMID- 29053646
TI  - Periapical implant lesion: A systematic review.
AB  - PURPOSE: The aim of this study was to systematically review the evidence for
      periapical implant lesion, which makes a patient more susceptible to the
      periapical lesion, frequency, symptoms, signs (including radiological findings)
      and possible treatment options. MATERIAL AND METHODS: A systematic literature
      review and analysis of publications included in PubMed, Embase and Cochrane;
      articles published until March 2016; with a populations, exposures and outcomes
      (PEO) search strategy was performed, focused on the issue: "In patients with
      periapical lesion to the implant during the osseointegration, what symptoms,
      signs, and changes in complementary examination manifested, for according to that
      stage, be intervened with the appropriate approach?". The set criteria for
      inclusion were peer-reviewed articles. RESULTS: From a total of 212 papers
      identified, 36 studies were included in this systematic review, with 15461
      implants evaluated and 183 periapical implant lesions. Which 8 papers included
      more than 5 cases and 28 included equal or less than 5 cases. Analysis of the
      papers revealed that periapical implant lesion is classified according to
      evolution stages into acute (non-suppurated and suppurated) and subacute (or
      suppurated-fistulized). In the acute stage and in the subacute if there is no
      loss of implant stability, the correct treatment approach is implant periapical
      surgery. In the subacute stage associated with implant mobility the implant must
      be removed. CONCLUSIONS: Evidence on the subject is very limited, there are few
      studies with small sample, without homogeneity of criteria for diagnosing the
      disease and without design of scientific evidence. Currently etiology lacks
      consensus. The early diagnosis of periapical implant periapical lesions during
      the osseointegration phase and early treatment, will lead to a higher survival
      rate of implants treated, hence preventing the need for implant extraction.

PMID- 29053647
TI  - Efficacy of different methods used for dry socket prevention and risk factor
      analysis: A systematic review.
AB  - BACKGROUND: Dry socket is one of the most common complications that develops
      after the extraction of a permanent tooth, and its prevention is more effective
      than its treatment. OBJECTIVES: Analyze the efficacy of different methods used in
      preventing dry socket in order to decrease its incidence after tooth extraction.
      MATERIAL AND METHODS: A Cochrane and PubMed-MEDLINE database search was conducted
      with the search terms "dry socket", "prevention", "risk factors", "alveolar
      osteitis" and "fibrynolitic alveolitis", both individually and using the Boolean
      operator "AND". The inclusion criteria were: clinical studies including at least
      30 patients, articles published from 2005 to 2015 and written in English. The
      exclusion criteria were case reports and nonhuman studies. RESULTS: 30
      publications were selected from a total of 250. Six of the 30 were excluded after
      reading the full text. The final review included 24 articles: 9 prospective
      studies, 2 retrospective studies and 13 clinical trials. They were stratified
      according to their level of scientific evidence using SIGN criteria (Scottish
      Intercollegiate Guidelines Network). CONCLUSIONS: All treatments included in the
      review were aimed at decreasing the incidence of dry socket. Locally
      administering chlorhexidine or applying platelet-rich plasma reduces the
      likelihood of developing this complication. Antibiotic prescription does not
      avoid postoperative complications after lower third molar surgery. With regard to
      risk factors, all of the articles selected suggest that patient age, history of
      previous infection and the difficulty of the extraction are the most common
      predisposing factors for developing dry socket. There is no consensus that
      smoking, gender or menstrual cycles are risk factors. Taking the scientific
      quality of the articles evaluated into account, a level B recommendation has been
      given for the proposed-procedures in the prevention of dry socket.

PMID- 29053648
TI  - Influence of clinical and psychological variables upon the oral health-related
      quality of life in patients with temporomandibular disorders.
AB  - BACKGROUND: To analyze the association between the OHIP-14 and the different
      subtypes making up the clinical and psychological axis obtained using the
      RDC/TMD. MATERIAL AND METHODS: 407 patients treated at the TMD unit of the
      Andalusian Healthcare Service were administered the Spanish version of the
      Research Diagnostic Criteria for Temporomandibular Disorders questionnaire
      (RDC/TMD), together with the Oral Health Impact Profile questionnaire (OHIP-14).
      The degree of association between the patients' score in the OHIP-14 and the
      clinical and biopsychosocial variables was analyzed through bivariate and
      multivariate analyses, specifically through linear regression. RESULTS: 89.4% of
      the treated patients were women, while 10.6% were men, with an average age of
      42.08 +/- 14.9 years. The mean score and standard deviation for the OHIP-14 was
      20.57 +/- 10.73. A significant association (p < 0.05) was observed with the
      following variables: Axis I, jaw disability checklist, depression, somatization,
      perceived pain duration, and pain interference with activities of daily living.
      CONCLUSIONS: The analysis of the relation between self-perceived health in
      patients with TMD, as measured by the OHIP-14, showed a R2 of 0.3979, with a
      higher Beta value for the association between the OHIP and patients with both
      myofascial pain and arthopathy, jaw disability, depression, a higher pain
      duration and a higher pain interference with activities of daily living.

PMID- 29053649
TI  - Oral and oropharyngeal squamous cell carcinoma in young adults: A retrospective
      study in Granada University Hospital.
AB  - BACKGROUND: This study aims to evaluate and analyze the clinical features and
      outcomes of oral and oropharyngeal squamous cell carcinoma (SCC) in patients < 45
      years old in our center. MATERIAL AND METHODS: A retrospective analysis was
      conducted using the records of patients diagnosed with oral and oropharyngeal SCC
      between 1998 and 2011 in the University Hospital of Granada (Spain). The analysis
      identified 33 patients with oral and oropharyngeal SCC with an age of <45 years.
      Moreover, during the years studied, a further 472 patients were diagnosed with
      oral and oropharyngeal SCC in our center. Thus, 100 SCC patients with an age of
      >45 years were randomly selected from the same database. A retrospective analysis
      was conducted to determine specific features including sites of occurrence, risk
      factors, sex distribution, socio-economic status, T stage at diagnosis, nodal
      involvement, degree of tumor differentiation, locoregional failure and overall
      survival at 5 years was. Further, the results of both groups were compared.
      RESULTS: The male-female ratio was 1.2:1 in the group of young adults and 2.03:1
      in the group of patients with an age of >45 years. No significant differences
      were found in terms of site, nodal involvement, locoregional failure, and overall
      survival. However, there were statistically significant differences between the
      two groups in terms of features such as risk factors, socio-economic status, T
      stage at diagnosis, and degree of tumor differentiation. The overall 5-year
      survival rate was 62% for patients >45 years old, whilst for the group of young
      adults this rate was 48.4% (p= 0.17). CONCLUSIONS: The poor association between
      the common risk factors and oral and oropharyngeal cancers in young adults
      suggests that other pathogenic mechanisms should be investigated. For young
      patients, the data show evidence of poorer outcomes in terms of overall survival
      (p=0.17), and locoregional failure (p=0.23). Nevertheless, the literature shows
      that the results in this field are particularly inconsistent, and further
      research is therefore needed to provide more in-depth knowledge of the disease in
      this age group.

PMID- 29053650
TI  - Quality of life after upper third molar removal: A prospective longitudinal
      study.
AB  - BACKGROUND: Third molar extraction is a very common procedure in Dentistry. The
      aim of this study was to evaluate the quality of life (QoL) and satisfaction of
      patients undergoing extraction of an upper third molar under local anesthesia. A
      second objective was to describe the evolution of self-reported pain measured in
      a visual analogue scale (VAS) in the 7 days after surgery and its relationship
      with pre- and intraoperative factors. MATERIAL AND METHODS: A prospective
      longitudinal cohort study was made. Fifty-five patients received a questionnaire
      assessing social and working isolation, eating and speaking ability, diet
      modifications, sleep impairment, physical appearance, discomfort at suture
      removal and overall satisfaction. Pain was registered daily on a VAS scale. A
      descriptive and bivariate analysis of the data was performed. RESULTS: Forty
      seven patients were included. Pain decreased lineally across the 7 days, and
      relief was significant between days 2 and 3. Intraoperative complications were
      significantly associated with pain. The complication that showed the highest pain
      score was the tuberosity fracture. CONCLUSIONS: Upper third molar removal
      significantly affects the patient's quality of life, particularly during the
      first 2 days after extraction.

PMID- 29053651
TI  - Association between obesity and periodontal disease. A systematic review of
      epidemiological studies and controlled clinical trials.
AB  - BACKGROUND: Obesity is a very prevalent chronic disease worldwide and has been
      suggested to increase susceptibility of periodontitis. The aim of this paper was
      to provide a systematic review of the association between obesity and periodontal
      disease, and to determine the possible mechanisms underlying in this
      relationship. MATERIAL AND METHODS: A literature search was carried out in the
      databases PubMed-Medline and Embase. Controlled clinical trials and observational
      studies identifying periodontal and body composition parameters were selected.
      Each article was subjected to data extraction and quality assessment. RESULTS: A
      total of 284 articles were identified, of which 64 were preselected and 28 were
      finally included in the review. All the studies described an association between
      obesity and periodontal disease, except two articles that reported no such
      association. Obesity is characterized by a chronic subclinical inflammation that
      could exacerbate other chronic inflammatory disorders like as periodontitis.
      CONCLUSIONS: The association between obesity and periodontitis was consistent
      with a compelling pattern of increased risk of periodontitis in overweight or
      obese individuals. Although the underlying pathophysiological mechanism remains
      unclear, it has been pointed out that the development of insulin resistance as a
      consequence of a chronic inflammatory state and oxidative stress could be
      implicated in the association between obesity and periodontitis. Further
      prospective longitudinal studies are needed to define the magnitude of this
      association and to elucidate the causal biological mechanisms.

PMID- 29053652
TI  - A report on the clinical-pathological correlations of 788 gingival lesion.
AB  - BACKGROUND: The diagnosis and treatment of a variety of non-plaque related
      gingival diseases have become an integrated aspect of everyday dentistry. The aim
      of this study was to analyse the relationship between clinical appearance and
      histopathological features of gingival lesions in a large Northern Italian
      population. MATERIAL AND METHODS: A retrospective study of 788 cases of gingival
      and alveolar mucosal biopsies was set up. Statistical analysis was performed by
      calculating the odds ratio and 95% confidence interval (C.I.), in order to assess
      the degree of association between the clinical parameters considered (primary
      lesions) and the single pathologies, statistically evaluated by Mantel-Haenszel
      tests. The correlation between clinical and histological diagnosis was classified
      as follow: 1) expected data (ED): provisional clinical diagnosis; 2) real data
      (RD): final histopathology diagnosis; 3) concordant data (CD): correspondence
      between the expected data and real data. The correlation was calculated as
      follow: CC (complete concordance) = CD x 100 / ED, this expressing the percentage
      in which the clinical and the histological diagnosis overlapped. RESULTS: The
      most frequently observed and biopsied primary lesions resulted to be exophytic,
      followed by mucosal colour changes and finally by losses of substance. The
      statistically significant association between primary lesion and their
      manifestation in gingival pathologies was reported. Volume increases, for
      instance, were positively correlated to plasma cell epulis, pyogenic granuloma,
      fibrous reactive hyperplasia and hemangioma. Verrucous-papillary lesions were
      most often seen in verrucous carcinoma, verrucous leukoplakia and mild dysplasia.
      White lesion resulted to be related to leukoplakia or oral lichen planus. Red
      lesions resulted to be related only oral lichen planus. Erosive vesicle-bullous
      lesions were linked to disimmune pathologies. Ulcerative lesions were positively
      associated to oral squamous cell cancer. Finally, potentially malignant disorders
      have the most percentage high concordance. Among the malignant lesions, the
      correlation increased up to the squamous cell carcinoma and leukaemia.
      CONCLUSIONS: This article presented the frequency and the clinico-pathological
      concordance of all primary lesions and the histopathological diagnosis of
      gingival lesions. For every primary lesion, it is possible to correlate a
      specific histopathological diagnosis in a statistical manner. This can be a
      valuable aid for not specialist clinicians who daily observe mucosae and have the
      opportunity to intercept major diseases.

PMID- 29053653
TI  - Patients with advanced oral squamous cell carcinoma have high levels of soluble E
      cadherin in the saliva.
AB  - BACKGROUND: The objective of this study was to assess the potential clinical
      value of the concentration of soluble salivary E-cadherin (sE-cadherin) compared
      with the clinical value of the presence of membranous E-cadherin (mE-cadherin) in
      oral squamous cell carcinoma tumor tissues. MATERIAL AND METHODS: Data regarding
      patient demographics, clinical stage, saliva and tumor tissue samples were
      collected. The saliva was analyzed for sE-cadherin protein levels and was
      compared to the mE-cadherin immunohistochemical expression levels in tumor
      tissues, which were assessed via the HercepTest(r) method. Patients without
      cancer were included in the study as a control group for comparisons of the sE
      cadherin levels. RESULTS: sE-cadherin levels in the saliva of patients without
      cancer were lower than those in patients with cancer, and the difference was
      statistically significant (p=0.031). Low mE-cadherin expression was statistically
      significantly associated with lymph node positivity (p=0.015) and advanced
      clinical stage (p=0.001). The inverse relationship between mE-cadherin and sE
      cadherin was significant in terms of lymph node positivity (p=0.014) and advanced
      clinical stage (p=0.037). CONCLUSIONS: The results suggest that sE-cadherin
      levels are significantly increased in patients with oral cancer and that its low
      expression within the membrane as well as the progression of the disease appear
      to be inversely associated with levels of sE-cadherin in the saliva.

PMID- 29053654
TI  - Retrospective analysis of jaw biopsies in young adults. A study of 1599 cases in
      Southern Brazil.
AB  - BACKGROUND: To evaluate the prevalence and the characteristics of jaw lesions
      diagnosed in young adults aged 20 to 30 years in a southern Brazil reference
      center, over a period of 25 years. And to analyze the concordance between
      clinical and histological diagnosis. MATERIAL AND METHODS: In this cross
      sectional retrospective study, the biopsies files from this center were retrieved
      and data regarding sex, age, bone localization, clinical and histological
      diagnosis were collected. The histological diagnosis were grouped into the
      categories Cystic lesions of odontogenic origin, Periapical inflammation,
      Odontogenic tumors, Bone diseases, Health tissue and Nonspecific diagnostic.
      Absolute and relative frequencies were estimated with descriptive analysis. The
      agreement between clinical and histological diagnosis was measured through Kappa
      statistic. RESULTS: A total of 18,181 histopathological analysis were performed
      during the period of the study, registering 1,599 jaw lesions in young adults.
      The average age of individuals was 24,59 years (SD 3,1). Nine hundred ninety-one
      (62%) lesions were found in females and 608 (38%) in males. More than half of
      pathologies were cystic lesions of odontogenic origin (822/51.4%), followed by
      periapical inflammation (282/17.6%). Regarding the site of lesions, more than
      half occurred in posterior mandible (877/54.8%), followed by posterior maxilla
      (339/21.2%). The most frequent entities were periapical cyst, chronic periapical
      granuloma, dental follicle and paradental cyst, corresponding to a total of 1,202
      (75.2%) evaluated cases. In relation to the analysis of concordance between
      clinical and histological diagnosis the general Kappa index was 0.5, which is
      considered moderate. Finally, the findings confirm data from literature about the
      most frequent jaw pathologies in young adults and serve as aid for preventive
      measures of some entities. Additionally, they can improve the formulation of
      differential diagnosis and the patient management.

PMID- 29053655
TI  - Assessment of pre and postoperative anxiety in patients undergoing ambulatory
      oral surgery in primary care.
AB  - BACKGROUND: To analyze the pre- and postoperative anxiety level in patients
      undergoing ambulatory oral surgery (AOS) in a primary healthcare center (PHC).
      MATERIAL AND METHODS: Prospective and descriptive clinical study on 45 patients
      who underwent AOS procedures in the dental clinic of a public PHC of Spain
      between April and September 2015. Anxiety analysis was carried out with pre- and
      postoperative anxiety-state (STAI-S), anxiety-trait (STAI-T) and dental anxiety
      (MDAS) questionnaires. A descriptive, inferential and binary logistic regression
      analysis were performed for the variables age, sex, educational level, previous
      experience of oral treatment, type of oral surgery, degree of third molar
      impaction, surgical time, intraoperative complications, postoperative
      complications, and pain score with a visual analogue scale (VAS). RESULTS: The
      majority were female (57.8%) with a mean age of 33.5+/-9.6 years. The most
      frequent procedure was the lower third molar removal (82.2%). The mean pain score
      on the VAS was 1.6+/-1.8. The incidence of complications was low (7.8%). There
      was a statistically significant association between post- and preoperative
      anxiety (r=0.56, p<0.001) and a correlation between pain score and postoperative
      anxiety (Rho= -0.35, p=0.02). The likelihood of postoperative anxiety was related
      to preoperative anxiety (OR=1.3, p=0.03). CONCLUSIONS: AOS in a PHC is safe and
      should be more encouraged in the public primary care. The emotional impact on
      users was relatively low, highlighting that the preoperative anxiety levels were
      higher than the postoperative ones. Psychological factors related to pre- and
      postoperative anxiety should be considered in the AOS carried out in PC.

PMID- 29053656
TI  - Is it necessary to alter anticoagulation therapy for tooth extraction in patients
      taking direct oral anticoagulants?
AB  - BACKGROUND: The number of patients using direct oral anticoagulants (DOACs)
      instead of vitamin K antagonists (VKA) is increasing and there is limited data on
      the safety of tooth extractions in patients taking DOACs. The aim of this study
      was to compare the amount of bleeding (AOB) and postoperative complications after
      tooth extractions between patients taking VKAs and patients taking DOACs without
      altering the anticoaguation therapy. MATERIAL AND METHODS: The study consisted of
      four groups: Direct thrombin inhibitor group, factor Xa inhibitor group, warfarin
      group and a control group. A single tooth was extracted in each patient and
      routine coagulation test values were recorded prior to extraction. AOB was
      measured for 20 minutes after tooth extraction. The patients were evaluated on
      2nd and 7th days after extraction for bleeding. Status of bleeding was classified
      as no bleeding, mild bleeding controlled by gauze pads, moderate bleeding
      controlled by hemostatic agents and severe bleeding required hospitalization.
      Analysis of variance, chi square test and correlation analysis were used for
      statistical analysis of data. RESULTS: A total of 84 patients (48 male, 36
      female) were included in this study. The mean age of patients was 57 (38-87)
      years. Mean AOB was 1388.6+/-913.0, 1909.29+/-1063.1, 3673+/-1415.4, 1593.33+/
      672.5 mg for direct thrombin inhibitor, factor Xa inhibitor, warfarin and control
      groups respectively. Mean AOB was significantly higher for warfarin group,
      compared to other groups (p<0.05). The number of patients showing mild and
      moderate bleeding was significantly higher in warfarin group compared to other
      groups on the 2nd postextraction day (p=0.001). No bleeding was occurred in
      control group on 2nd and 7th postextraction days and no bleeding was occurred in
      direct thrombin inhibitor group on 7th postextraction day. The number of bleeding
      events among groups was not statistically significant on 7th postextraction day
      (p=0.251). CONCLUSIONS: Patients taking warfarin had more bleeding compared to
      patients taking direct oral anticoagulants after tooth extractions. In patients
      taking direct oral anticoagulants simple tooth extractions can be safely carried
      out without altering the anticaogulant regimen with the use of local hemostatic
      agents.

PMID- 29053657
TI  - Histological differences in the adherence of connective tissue to laser-treated
      abutments and standard abutments for dental implants. An experimental pilot study
      in humans.
AB  - BACKGROUND: The goal of the current study is to assess the difference in
      connective tissue adherence to laser microtextured versus machined titanium
      abutments. MATERIAL AND METHODS: Six patients were selected and each of them
      received 2 implants, one combined with a laser treated abutment and one with a
      machined abutment. After three months, the abutments were retrieved together with
      their surrounding gingival tissue for histological analysis. Qualitative and
      quantitative evaluation of microscopical images was performed to assess the
      presence or absence of adherence between the soft tissues and the abutment, and
      the percentage of soft tissue adhered to the two different surfaces. RESULTS:
      Intimate adherence between connective tissue and the laser treated abutments,
      while on machined abutments no adherence was detected. A significant difference
      was found in the percentage of surface in contact with soft tissue between both
      implant abutments p=0.03. CONCLUSIONS: Within the limitation of the current
      study, it can be concluded that connective tissues show enhanced adherence to
      microtextured abutments compared to machined abutments.

PMID- 29053658
TI  - Low-level laser therapy for treatment of neurosensory disorders after
      orthognathic surgery: A systematic review of randomized clinical trials.
AB  - BACKGROUND: Low-level laser has been widely used in Dentistry and many studies
      have focused on its application in oral surgeries. This study was conducted with
      the aim of searching for scientific evidence concerning the effectiveness of
      laser to reduce pain or paresthesia related to orthognathic surgery. MATERIAL AND
      METHODS: An electronic search was performed in PubMed, Scopus, Science Direct,
      LILACS, SciELO, CENTRAL, Google Scholar, OpenGrey, and ClinicalTrials.gov, up to
      November 2016, with no restrictions on language or year of publication.
      Additionally, a hand search of the reference list of the selected studies was
      carried out. The PICOS strategy was used to define the eligibility criteria and
      only randomized clinical trials were selected. RESULTS: Out of 1,257 identified
      citations, three papers fulfilled the criteria and were included in the
      systematic review. The risk of bias was assessed according to the Cochrane
      Guidelines for Clinical Trials and results were exposed based on a descriptive
      analysis. One study showed that laser therapy was effective to reduce
      postoperative pain 24 hours (P=0.007) and 72 hours (P=0.007) after surgery. Other
      study revealed the positive effect of laser to improve neurosensory recovery 60
      days after surgery, evaluated also by the two-point discrimination (P=0.005) and
      sensory (P=0.008) tests. The third study reported an improvement for general
      sensibility of 68.75% for laser group, compared with 21.43% for placebo
      (P=0.0095), six months after surgery. CONCLUSIONS: Individual studies suggested a
      positive effect of low-level laser therapy on reduction of postoperative pain and
      acceleration of improvement of paresthesia related to orthognathic surgery.
      However, due to the insufficient number and heterogeneity of studies, a meta
      analysis evaluating the outcomes of interest was not performed, and a pragmatic
      recommendation about the use of laser therapy is not possible. This systematic
      review was conducted according to the statements of PRISMA and was registered at
      PROSPERO under the number CRD42016043258.

PMID- 29053659
TI  - Impact of temporomandibular disorders on the stomatognathic system in children.
AB  - BACKGROUND: To evaluate the EMG activity and thickness of right masseter (RM),
      left masseter (LM), right temporal (RT) and left temporal (LT) muscles and bite
      force in children with temporomandibular disorders (TMD). MATERIAL AND METHODS:
      Forty five children (mean age 8.8 years; 22 boys and 23 girls) were examined on
      the basis of the RDC/TMD and the Faces Pain Scale-Revised (FPS-R) was used to
      determine the level of severity of the signs and symptoms of TMD, resulting in
      four groups: GI - without TMD (n=10); GII - with mild TMD (n=18), GIII: with
      moderate TMD (n=12) and GIV: with severe TMD (n=5). The data of electromyographic
      activity, maximum bite force and muscle thickness were tabulated and submitted to
      statistical analysis (ANOVA, P<=0.05). RESULTS: Children with TMD signs and
      symptoms had lower EMG activity than children of the control group. There was
      significant difference among the groups for the LT at rest (P=0.01), right
      (P=0.03) and left (P=0.05) laterality, and for the LM (P=0.01) and LT (P=0.03)
      muscles in maximum voluntary contraction. There were no statistically significant
      differences among the groups regarding muscle thickness. The bite force was lower
      in the TMD groups than children of the control group, with significant
      statistical difference for the right region (P=0.03). CONCLUSIONS: The severity
      of TMD signs and symptoms affected the EMG activity and the molar bite force in
      children. However, structural changes in the thickness of masticatory muscles are
      not perceptible in children with TMD signs and symptoms.

PMID- 29053660
TI  - The assessment of surgical and non-surgical treatment of stage II medication
      related osteonecrosis of the jaw.
AB  - BACKGROUND: Non-surgical treatment has generally been recommended for stage II
      medication-related osteonecrosis of the jaw (MRONJ) in preference to surgery.
      However, non-surgical treatment is not empirically effective. The aim of this
      study was to evaluate whether surgical or non-surgical treatment leads to better
      outcomes for stage II MRONJ. MATERIAL AND METHODS: In this retrospective study,
      surgery was performed in a total of 28 patients while 24 patients underwent non
      surgical treatment. The outcomes of both treatment approaches after 6 months were
      evaluated and statistically compared. In addition, risk factors for surgical and
      non-surgical treatments were assessed for each. RESULTS: Surgical treatment in 25
      patients (89.3%) resulted in success, with failure in 3 patients (10.7%). Non
      surgical treatment was successful for 8 patients (33.3%) and failed in 16
      patients (66.7%). There was therefore a significant difference between surgical
      and non-surgical treatment outcomes (P<0.01). Regarding risk factors, in non
      surgical treatment primary diseases, medications, and drug holiday had a
      significant effect on outcomes (P<0.01). Risk factors for surgical treatment
      could not be clarified. CONCLUSIONS: Surgical treatment is more effective than
      non-surgical treatment for stage II MRONJ, and drug holiday, primary disease, and
      medication constitute risk factors in non-surgical treatment.

PMID- 29053661
TI  - Evaluation of Kharma scale as a predictor of lower third molar extraction
      difficulty.
AB  - BACKGROUND: The Evaluation of the degree of lower third molar (L3M) extraction
      difficulty is extremely important for both clinicians and patients. This study
      aimed to evaluate the validity of a new index (Kharma scale) as a preoperative
      predictor index of the difficulty of surgical removal of impacted L3M. MATERIAL
      AND METHODS: Extraction difficulty of a series of 49-impacted L3M was predicted
      preoperatively by Kharma scale, and postoperative difficulty was assessed with a
      modified Parant scale. RESULTS: The sensitivity of Kharma scale, as a predictor
      of difficulty, was 18.2% and the specificity was 68.4%. Likelihood ratios for the
      Kharma categories also indicated that the scale is of little value for predicting
      a difficult extraction. There was no significant association between the Kharma
      score and duration of operation, but high-modified Parant scores were
      significantly associated with longer operations. CONCLUSIONS: The proposed Kharma
      scale was unreliable as preoperative predictor of the L3M extraction difficulty,
      and both radiological and clinical information must be taken into account.

PMID- 29053663
TI  - We must start applying author processing charges.

PMID- 29053662
TI  - High Expression of S100A6 Predicts Unfavorable Prognosis of Lung Squamous Cell
      Cancer.
AB  - BACKGROUND S100 family of proteins is mainly involved in regulation of
      intracellular calcium homeostasis. Aberrant expression of S100 family members has
      been reported in many types of cancers. However, as a member of S100 family, the
      prognostic value of S100A6 for lung squamous cell carcinoma (SCC) has not been
      well-studied. MATERIAL AND METHODS Using immunohistochemistry, we investigated
      the expression of S100A6 in 177 patients with SCC and further divided the cohort
      into a high S100A6 expression group and a low S100A6 expression group. The chi
      square test was applied to analyze the correlation between S100A6 expression and
      clinicopathological factors. Univariate analysis using the Kaplan-Meier method
      was performed to compare the difference in survival rates between the high S100A6
      expression group and the low S100A6 expression group; multivariate analysis with
      Cox regression model was used to identify independent prognostic risk factors.
      RESULTS In our experiment, we demonstrated that the expression of S100A6 was
      significantly associated with patient age and tumor differentiation. High
      expression of S100A6 was shown to be substantially related to the unfavorable
      prognosis of SCC. Moreover, our results confirmed that S100A6 was an independent
      risk factor for SCC prognosis, and could predict unfavorable prognosis.
      CONCLUSIONS High-expression of S100A6 was identified as an independent
      unfavorable prognostic factor for SCC, suggesting that targeting S100A6 may
      result in the development of potential targeted drug for SCC.

PMID- 29053664
TI  - Scientific production of Vice Chancellors for Research in Peruvian universities
      with a medical school.
AB  - OBJECTIVES: To determine the scientific production of Research Vice-chancellors
      at Peruvian universities that have medical schools, as well as their academic
      degrees as an indirect way to evaluate their suitability for the position they
      hold. METHODS: We searched all Peruvian universities that register medical
      schools. Of these, the scientific production of the universities registered in
      SCOPUS was identified in September of the 2016. The scientific production of the
      vice chancellors of investigation of these faculties of medicine was determined
      through the search of its scientific publications registered in SCOPUS and those
      reported in the National Registry of Researchers in Science and Technology.
      Academic degrees were obtained from the database of the National Superintendence
      of Higher University Education. RESULTS: The sample included 28 research vice
      chancellors. Only 4/28 had any publications. The average number of articles
      published by the vice chancellors of research was 1.71, the number of citations
      23.1 on average and the H index 0.64. Besides, 22 Vice-chancellors of research
      had the degree of doctor, four had the degree of bachelor and two the degree of
      master. CONCLUSIONS: The scientific production of research vice chancellors is
      poor. The required academic grade requirement for the position is not met in all
      cases. It is likely that, having no research experience, his leadership in
      directing a university's research policies may be questioned.

PMID- 29053665
TI  - Is duloxetine an alternative in the treatment of osteoarthritis?
AB  - INTRODUCTION: Many osteoarthritis patients continue to present symptoms despite
      nonsurgical treatment. Duloxetine might be a viable alternative for such cases,
      but real clinical relevance remains unclear. METHODS: A literature review was
      conducted in Epistemonikos, the largest database for systematic reviews in health
      that compiles multiple sources, including MEDLINE, EMBASE, and Cochrane, among
      others. Relevant data were extracted, and information from the primary studies
      was reanalyzed. A subsequent meta-analysis was conducted, and summary of findings
      tables were constructed using the GRADE methodology. RESULTS AND CONCLUSIONS:
      Four systematic reviews including four randomized trials, were identified. In
      conclusion, while duloxetine slightly improves pain and functionality in
      osteoarthritis patients, its use is associated with frequent adverse side
      effects. Therefore, the benefit/risk balance appears unfavorable.

PMID- 29053666
TI  - Experimental Implementation of a New Composite Fabrication Method: Exposing Bare
      Fibers on the Composite Surface by the Soft Layer Method.
AB  - The bipolar plate is a key component in proton exchange membrane fuel cells
      (PEMFCs) and vanadium redox flow batteries (VRFBs). It is a multi-functional
      component that should have high electrical conductivity, high mechanical
      properties, and high productivity. In this regard, a carbon fiber/epoxy resin
      composite can be an ideal material to replace the conventional graphite bipolar
      plate, which often leads to the catastrophic failure of the entire system because
      of its inherent brittleness. Though the carbon/epoxy composite has high
      mechanical properties and is easy to manufacture, the electrical conductivity in
      the through-thickness direction is poor because of the resin-rich layer that
      forms on its surface. Therefore, an expanded graphite coating was adopted to
      solve the electrical conductivity issue. However, the expanded graphite coating
      not only increases the manufacturing costs but also has poor mechanical
      properties. In this study, a method to expose fibers on the composite surface is
      demonstrated. There are currently many methods that can expose fibers by surface
      treatment after the fabrication of the composite. This new method, however, does
      not require surface treatment because the fibers are exposed during the
      manufacture of the composite. By exposing bare carbon fibers on the surface, the
      electrical conductivity and mechanical strength of the composite are increased
      drastically.

PMID- 29053667
TI  - Assay Development for High Content Quantification of Sod1 Mutant Protein
      Aggregate Formation in Living Cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that can
      be caused by inherited mutations in the gene encoding copper-zinc superoxide
      dismutase 1 (SOD1). The structural instability of SOD1 and the detection of SOD1
      positive inclusions in familial-ALS patients supports a potential causal role for
      misfolded and/or aggregated SOD1 in ALS pathology. In this study, we describe the
      development of a cell-based assay designed to quantify the dynamics of SOD1
      aggregation in living cells by high content screening approaches. Using
      lentiviral vectors, we generated stable cell lines expressing wild-type and
      mutant A4V SOD1 tagged with yellow fluorescent protein and found that both
      proteins were expressed in the cytosol without any sign of aggregation.
      Interestingly, only SOD1 A4V stably expressed in HEK-293, but not in U2OS or SH
      SY5Y cell lines, formed aggregates upon proteasome inhibitor treatment. We show
      that it is possible to quantify aggregation based on dose-response analysis of
      various proteasome inhibitors, and to track aggregate-formation kinetics by time
      lapse microscopy. Our approach introduces the possibility of quantifying the
      effect of ALS mutations on the role of SOD1 in aggregate formation as well as
      screening for small molecules that prevent SOD1 A4V aggregation.

PMID- 29053668
TI  - Laboratory Protocol for Genetic Gut Content Analyses of Aquatic
      Macroinvertebrates Using Group-specific rDNA Primers.
AB  - Analyzing food webs is essential for a better understanding of ecosystems. For
      example, food web interactions can undergo severe changes caused by the invasion
      of non-indigenous species. However, an exact identification of field predator
      prey interactions is difficult in many cases. These analyses are often based on a
      visual evaluation of gut content or the analysis of stable isotope ratios
      (delta15N and delta13C). Such methods require comprehensive knowledge about,
      respectively, morphologic diversity or isotopic signature from individual prey
      organisms, leading to obstacles in the exact identification of prey organisms.
      Visual gut content analyses especially underestimate soft bodied prey organisms,
      because maceration, ingestion and digestion of prey organisms make identification
      of specific species difficult. Hence, polymerase chain reaction (PCR) based
      strategies, for example the use of group-specific primer sets, provide a powerful
      tool for the investigation of food web interactions. Here, we describe detailed
      protocols to investigate the gut contents of macroinvertebrate consumers from the
      field using group-specific primer sets for nuclear ribosomal deoxyribonucleic
      acid (rDNA). DNA can be extracted either from whole specimens (in the case of
      small taxa) or out of gut contents of specimens collected in the field. Presence
      and functional efficiency of the DNA templates need to be confirmed directly from
      the tested individual using universal primer sets targeting the respective
      subunit of DNA. We also demonstrate that consumed prey can be determined further
      down to species level via PCR with unmodified group-specific primers combined
      with subsequent single strand conformation polymorphism (SSCP) analyses using
      polyacrylamide gels. Furthermore, we show that the use of different fluorescent
      dyes as labels enables parallel screening for DNA fragments of different prey
      groups from multiple gut content samples via automated fragment analysis.

PMID- 29053669
TI  - The Other End of the Leash: An Experimental Test to Analyze How Owners Interact
      with Their Pet Dogs.
AB  - It has been suggested that the way in which owners interact with their dogs can
      largely vary and influence the dog-owner bond, but very few objective studies, so
      far, have addressed how the owner interacts with the dog. The goal of the present
      study was to record dog owners' interaction styles by means of objective
      observation and coding. The experiment included eight standardized situations in
      which owners of pet dogs were asked to perform specific tasks including both
      positive (i.e. playing, teaching a new task, showing a preference towards an
      object in a food searching task, greeting after separation) and potentially
      distressing tasks (i.e. physical restriction during DNA sampling, putting a T
      shirt onto the dog, giving basic obedience commands while the dog was
      distracted). The video recordings were coded off-line using a specifically
      designed coding scheme including scores for communication, social support,
      warmth, enthusiasm, and play style, as well as frequency of behaviors like
      petting, praising, commands, and attention sounds. Exploratory Factor Analysis of
      the 20 variables measured revealed 3 factors, labeled as Owner Warmth, Owner
      Social Support, and Owner Control, which can be viewed as analogues to parenting
      style dimensions. The experimental procedure introduced here represents the first
      standardized measure of interaction styles of dog owners. The methodology
      presented here is a useful tool to investigate individual variation in the
      interaction style of pet dog owners that can be used to explain differences in
      the dog-human relationship, dogs' behavioral outcomes, and dogs stress coping
      strategies, all crucial elements both from a theoretical and applied point of
      view.

PMID- 29053670
TI  - Pattern-based Search of Epigenomic Data Using GeNemo.
AB  - Compared with the robust text-based search tools for genomic or RNA sequencing
      data, current methodologies for pattern-based searches of epigenomic and other
      functional genomic data are very limited. GeNemo is the first online search tool
      that accomplishes this goal. Users input their functional genomic data in the
      Browser Extensible Data (BED), Peaks, and bigWig formats, and may search for data
      in any of the three formats. Users may specify which types of datasets to search
      against, choosing from a variety of online datasets, with the Encyclopedia of DNA
      Elements (ENCODE) representing different epigenomic marks, transcriptional factor
      binding sites, and chromatin hypersensitivities or accessibilities in specific
      cell types, and developmental stages or species (mouse or human). GeNemo returns
      a list of genomic regions with matching patterns to the input data, which may be
      viewed in the browser as well as downloaded in the BED file format. The upgraded
      GeNemo has improved graphical display, has more robust interface, and is no
      longer prone to errors due to changes in the University of California, Santa Cruz
      (UCSC) genome browser. Troubleshooting steps for common problems are discussed.
      As the amount of functional genomic data is expanding exponentially, there is a
      critical need to develop and refine new bioinformatic tools such as GeNemo for
      data analyses and interpretation.

PMID- 29053671
TI  - Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput
      Measurement of Lipid Peroxidation in High Density Lipoprotein.
AB  - Low high-density lipoprotein cholesterol (HDL-C) levels are one of the most
      powerful independent negative predictors of atherosclerotic cardiovascular
      disease (CVD). The structure and function of HDL rather than HDL-C may more
      accurately predict atherosclerosis. Several HDL protein and lipid compositional
      changes that impair HDL function occur in inflammatory states such as
      atherosclerosis. HDL function is usually determined by cell based assays such as
      cholesterol efflux assay but these assays have numerous drawbacks lack of
      standardization. Cell-free assays may give more robust measures of HDL function
      compared to cell-based assays. HDL oxidation impairs HDL function. HDL has a
      major role in lipid peroxide transport and high amount of lipid peroxides is
      related to abnormal HDL function. Lipid-probe interactions should be considered
      when interpreting the results of non-enzymatic fluorescence assays for measuring
      the lipid oxidative state. This motivated us to develop a cell-free biochemical
      enzymatic method to assess HDL lipid peroxide content (HDLox) that contributes to
      HDL dysfunction. This method is based on the enzyme horseradish peroxidase (HRP)
      and the fluorochrome Amplex Red that can quantify (without cholesterol oxidase)
      the lipid peroxide content per mg of HDL-C. Here a protocol is describedfor
      determination of HDL-lipid peroxidation using the fluorochrome reagent. Assay
      variability can be reduced by strict standardization of experimental conditions.
      Higher HDLox values are associated with reduced HDL antioxidant function. The
      readout of this assay is associated with readouts of validated cell-based assays,
      surrogate measures of cardiovascular disease, systemic inflammation, immune
      dysfunction, and associated cardiovascular and metabolic risk phenotypes. This
      technical approach is a robust method to assess HDL function in human disease
      where systemic inflammation, oxidative stress and oxidized lipids have a key role
      (such as atherosclerosis).

PMID- 29053672
TI  - Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin
      and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor
      bearing Mice.
AB  - Combination chemotherapy is frequently used in the clinic for cancer treatment;
      however, associated adverse effects to normal tissue may limit its therapeutic
      benefit. Nanoparticle-based drug combination has been shown to mitigate the
      problems encountered by free drug combination therapy. Our previous studies have
      shown that the combination of two anticancer drugs, doxorubicin (DOX) and
      mitomycin C (MMC), produced a synergistic effect against both murine and human
      breast cancer cells in vitro. DOX and MMC co-loaded polymer-lipid hybrid
      nanoparticles (DMPLN) bypassed various efflux transporter pumps that confer
      multidrug resistance and demonstrated enhanced efficacy in breast tumor models.
      Compared to conventional solution forms, such superior efficacy of DMPLN was
      attributed to the synchronized pharmacokinetics of DOX and MMC and increased
      intracellular drug bioavailability within tumor cells enabled by the nanocarrier
      PLN. To evaluate the pharmacokinetics and bio-distribution of co-administered DOX
      and MMC in both free solution and nanoparticle forms, a simple and efficient
      multi-drug analysis method using reverse-phase high performance liquid
      chromatography (HPLC) was developed. In contrast to previously reported methods
      that analyzed DOX or MMC individually in the plasma, this new HPLC method is able
      to simultaneously quantitate DOX, MMC and a major cardio-toxic DOX metabolite,
      doxorubicinol (DOXol), in various biological matrices (e.g., whole blood, breast
      tumor, and heart). A dual fluorescent and ultraviolet absorbent probe 4
      methylumbelliferone (4-MU) was used as an internal standard (I.S.) for one-step
      detection of multiple drug analysis with different detection wavelengths. This
      method was successfully applied to determine the concentrations of DOX and MMC
      delivered by both nanoparticle and solution approaches in whole blood and various
      tissues in an orthotopic breast tumor murine model. The analytical method
      presented is a useful tool for pre-clinical analysis of nanoparticle-based
      delivery of drug combinations.

PMID- 29053673
TI  - A Chronic Cardiac Ischemia Model in Swine Using an Ameroid Constrictor.
AB  - Cardiovascular disease remains the number one cause of mortality in the United
      States. There are numerous approaches to treating these diseases, but regardless
      of the approach, an in vivo model is needed to test each treatment. The pig is
      one of the most used large animal models for cardiovascular disease. Its heart is
      very similar in anatomy and function to that of a human. The ameroid placement
      technique creates an ischemic area of the heart, which has many useful
      applications in studying myocardial infarction. This model has been used for
      surgical research, pharmaceutical studies, imaging techniques, and cell
      therapies. There are several ways of inducing an ischemic area in the heart. Each
      has its advantages and disadvantages, but the placement of an ameroid constrictor
      remains the most widely used technique. The main advantages to using the ameroid
      are its prevalence in existing research, its availability in various sizes to
      accommodate the anatomy and size of the vessel to be constricted, the surgery is
      a relatively simple procedure, and the post-operative monitoring is minimal,
      since there are no external devices to maintain. This paper provides a detailed
      overview of the proper technique for the placement of the ameroid constrictor.

PMID- 29053674
TI  - Assessing Urinary Tract Junction Obstruction Defects by Methylene Blue Dye
      Injection.
AB  - Urinary tract junction obstruction defects are congenital anomalies inducing
      hydronephrosis and hydroureter. Murine urinary tract junction obstruction defects
      can be assessed by tracking methylene blue dye flow within the urinary system.
      Methylene blue dye is injected into the renal pelvis of perinatal embryonic
      kidneys and dye flow is monitored from the renal pelvis of the kidney through the
      ureter and into the bladder lumen after applying hydrostatic pressure. Dye
      accumulation will be evident in the bladder lumen of the normal perinatal urinary
      tract, but will be constrained between the renal pelvis and the end point of an
      abnormal ureter, if urinary tract obstructions occur. This method facilitates the
      confirmation of urinary tract junction obstructions and visualization of
      hydronephrosis and hydroureter. This manuscript describes a protocol for
      methylene blue dye injection into the renal pelvis to confirm urinary tract
      junction obstructions.

PMID- 29053675
TI  - Transcanalicular Diode Laser-assisted Dacryocystorhinostomy for the Treatment of
      Primary Acquired Nasolacrimal Duct Obstruction.
AB  - Today's gold standard in the treatment of infrasaccal primary acquired
      nasolacrimal duct obstruction (PANDO) is external dacryocystorhinostomy (DCR), a
      relatively invasive procedure that can be performed after failure of recanalizing
      treatments. However, with progress in the field of diode laser technology, new
      approaches have emerged. Laser-assisted transcanalicular DCR with subsequent
      bicanalicular silicon intubation is a new option showing great promise as a
      viable minimally invasive procedure. Under permanent endoscopic visual control
      from the nasal cavity, a diode laser fiber is inserted into the lacrimal sac and
      laser energy is applied to create a bony ostium between the lacrimal sac and the
      nasal cavity. Since no skin incision needs to be made, advantages of this method
      comprise the sparing of the skin as well as the medial palpebral structures and
      the physiological palpebral-canalicular pump mechanism. The duration of surgery
      as well as reconvalescence is generally shorter than with external DCR.
      Complications include silicon tube prolapse, mild swelling and, rarely,
      canalicular infection and thermal injury. One-year functional success rates,
      defined as complete resolution of symptoms and ostium patency, are high, yet
      still range behind those of external DCR. However, secondary external DCR after
      failure of laser-assisted DCR can be performed without difficulty. Thus, laser
      assisted transcanalicular DCR is a valid option that should be considered as a
      second-step procedure after failure of recanalization procedures and before
      external DCR.

PMID- 29053676
TI  - Laminotomy for Lumbar Dorsal Root Ganglion Access and Injection in Swine.
AB  - Dorsal root ganglia (DRG) are anatomically well defined structures that contain
      all primary sensory neurons below the head. This fact makes DRG attractive
      targets for injection of novel therapeutics aimed at treating chronic pain. In
      small animal models, laminectomy has been used to facilitate DRG injection
      because it involves surgical removal of the vertebral bone surrounding each DRG.
      We demonstrate a technique for intraganglionic injection of lumbar DRG in a large
      animal species, namely, swine. Laminotomy is performed to allow direct access to
      DRG using standard neurosurgical techniques, instruments, and materials. Compared
      with more extensive bone removal via laminectomy, we implement laminotomy to
      conserve spinal anatomy while achieving sufficient DRG access. Intraoperative
      progress of DRG injection is monitored using a non-toxic dye. Following
      euthanasia on post-operative day 21, the success of injection is determined by
      histology for intraganglionic distribution of 4',6-diamidino-2-phenylindole
      (DAPI). We inject a biologically inactive solution to demonstrate the protocol.
      This method could be applied in future preclinical studies to target therapeutic
      solutions to DRG. Our methodology should facilitate testing the translatability
      of intraganglionic small animal paradigms in a large animal species.
      Additionally, this protocol may serve as a key resource for those planning
      preclinical studies of DRG injection in swine.

PMID- 29053677
TI  - Building Double-decker Traps for Early Detection of Emerald Ash Borer.
AB  - Emerald ash borer (EAB) (Agrilus planipennis Fairmaire), the most destructive
      forest insect to have invaded North America, has killed hundreds of millions of
      forest and landscape ash (Fraxinus spp.) trees. Several artificial trap designs
      to attract and capture EAB beetles have been developed to detect, delineate, and
      monitor infestations. Double-decker (DD) traps consist of two corrugated plastic
      prisms, one green and one purple, attached to a 3 m tall polyvinyl chloride (PVC)
      pipe supported by a t-post. The green prism at the top of the PVC pipe is baited
      with cis-3-hexenol, a compound produced by ash foliage. Surfaces of both prisms
      are coated with sticky insect glue to capture adult EAB beetles. Double-decker
      traps should be placed near ash trees but in open areas, exposed to sun. Double
      decker trap construction and placement are presented here, along with a summary
      of field experiments demonstrating the efficacy of DD traps in capturing EAB
      beetles. In a recent study in sites with relatively low EAB densities, double
      decker traps captured significantly more EAB than green or purple prism traps or
      green funnel traps, all of which are designed to be suspended from a branch in
      the canopy of ash trees. A greater percentage of double decker traps were
      positive, i.e., captured at least one EAB, than the prism traps or funnel traps
      that were hung in ash tree canopies.

PMID- 29053678
TI  - Assay for Phosphorylation and Microtubule Binding Along with Localization of Tau
      Protein in Colorectal Cancer Cells.
AB  - The microtubule-associated protein tau is a neuronal protein that localizes
      mostly in axons. Generally tau is essential for normal neuronal functioning
      because it is involved in microtubule assembly and stabilization. Besides
      neurons, tau is expressed in human breast, prostate, gastric, colorectal, and
      pancreatic cancers where it shows nearly similar structure and exerts similar
      functions as the neuronal tau. The amount of tau and its phosphorylation can
      change its function as a stabilizer of microtubules, and lead to the development
      of paired helical filaments in different neurodegenerative disorders, such as
      Alzheimer's disease. Determining the phosphorylation state of tau and its
      microtubule-binding characteristics is important. In addition, examining the
      intracellular localization of tau is important in different diseases. This
      manuscript details standard protocols for measuring tau phosphorylation and tau
      binding to microtubules in colorectal cancer cells with or without curcumin and
      LiCl treatment. These treatments can be used to stop cancer cell proliferation
      and development. Intracellular localization of tau is examined by using
      immunohistochemistry and confocal microscopy while using low amounts of
      antibodies. These assays can be used repetitively for screening compounds that
      affect tau hyperphosphorylation or microtubule binding. Novel therapeutics used
      for different tauopathies or related anticancer agents can potentially be
      characterized using these protocols.

PMID- 29053679
TI  - Measuring the Effect of Chemicals on the Growth and Reproduction of
      Caenorhabditis elegans.
AB  - Toxicological evaluation is crucial for understanding the effects of chemicals on
      living organisms in basic and applied biological science fields. A non-mammalian
      soil round worm, Caenorhabditis elegans, is a valuable model organism for
      toxicology studies due to its convenience and lack of animal ethics issues
      compared with mammalian animal systems. In this protocol, a detailed procedure of
      toxicological evaluation of chemicals in C. elegans is described. A clinical
      anticancer drug, etoposide, which targets human topoisomerase II and inhibits DNA
      replication of human cancer cells, was selected as a model testing chemical. Age
      synchronized C. elegans eggs were exposed to either dimethyl sulfoxide (DMSO) or
      etoposide, and then the growth of C. elegans was monitored every day for 4 days
      by the stereo microscope observation. The total number of eggs laid from C.
      elegans treated with DMSO or etoposide was also counted by using the stereo
      microscope. Etoposide treatment significantly affected the growth and
      reproduction of C. elegans. By comparison of the total number of eggs laid from
      worms with different treatment periods of chemicals, it can be decided that the
      reproductive toxicity of chemicals on C. elegans reproduction is reversible or
      irreversible. These protocols may be helpful for both the development of various
      drugs and risk assessment of environmental toxicants.

PMID- 29053680
TI  - Evaluating In Vitro DNA Damage Using Comet Assay.
AB  - DNA damage is a common phenomenon for each cell during its lifespan, and is
      defined as an alteration of the chemical structure of genomic DNA. Cancer
      therapies, such as radio- and chemotherapy, introduce enormous amount of
      additional DNA damage, leading to cell cycle arrest and apoptosis to limit cancer
      progression. Quantitative assessment of DNA damage during experimental cancer
      therapy is a key step to justify the effectiveness of a genotoxic agent. In this
      study, we focus on a single cell electrophoresis assay, also known as the comet
      assay, which can quantify single and double-strand DNA breaks in vitro. The comet
      assay is a DNA damage quantification method that is efficient and easy to
      perform, and has low time/budget demands and high reproducibility. Here, we
      highlight the utility of the comet assay for a preclinical study by evaluating
      the genotoxic effect of olaparib/temozolomide combination therapy to U251 glioma
      cells.

PMID- 29053681
TI  - A Performance-testing Platform for a Conduction Micropump with an FR-4 Copper
      clad Electrode Plate.
AB  - Here, a conduction micropump with symmetric planar electrode pairs prepared on
      flame-retardant glass-reinforced epoxy (FR-4) copper-clad laminate (CCL) is
      fabricated. It is used to investigate the influence of chamber dimensions on the
      performance of a conduction micropump and to determine the reliability of the
      conduction pump when acetone is used as the working fluid. A testing platform is
      set up to evaluate conduction micropump performance under different conditions.
      When the chamber height is 0.2 mm, the pump pressure reaches its peak value.

PMID- 29053682
TI  - Implantation of Chronic Silicon Probes and Recording of Hippocampal Place Cells
      in an Enriched Treadmill Apparatus.
AB  - An important requisite for understanding brain function is the identification of
      behavior and cell activity correlates. Silicon probes are advanced electrodes for
      large-scale electrophysiological recording of neuronal activity, but the
      procedures for their chronic implantation are still underdeveloped. The activity
      of hippocampal place cells is known to correlate with an animal's position in the
      environment, but the underlying mechanisms are still unclear. To investigate
      place cells, here we describe a set of techniques which range from the
      fabrication of devices for chronic silicon probe implants to the monitoring of
      place field activity in a cue-enriched treadmill apparatus. A micro-drive and a
      hat are built by fitting and fastening together 3D-printed plastic parts. A
      silicon probe is mounted on the micro-drive, cleaned, and coated with dye. A
      first surgery is performed to fix the hat on the skull of a mouse. Small
      landmarks are fabricated and attached to the belt of a treadmill. The mouse is
      trained to run head-fixed on the treadmill. A second surgery is performed to
      implant the silicon probe in the hippocampus, following which broadband
      electrophysiological signals are recorded. Finally, the silicon probe is
      recovered and cleaned for reuse. The analysis of place cell activity in the
      treadmill reveals a diversity of place field mechanisms, outlining the benefit of
      the approach.

PMID- 29053683
TI  - New Application of an Atmospheric Pressure Plasma Jet as a Neuro-protective Agent
      Against Glucose Deprivation-induced Injury of SH-SY5Y Cells.
AB  - The atmospheric pressure plasma jet (APPJ) has attracted the attention of many
      researchers from multiple disciplines in recent years because its emissions
      include multiple types of reactive nitrogen species (RNS) and reactive oxygen
      species (ROS). Our previous study has shown the cytoprotective effect of the APPJ
      against oxidative stress-induced injuries. The aim of the present study is to
      provide a detailed in vitro treatment protocol regarding the neuroprotective
      applications of helium APPJs on glucose deprivation-induced injury in SH-SY5Y
      cells. The SH-SY5Y human neuroblastoma-derived cell line was maintained in RPMI
      1640 medium supplemented with 15% fetal calf serum. The culture medium was then
      changed to RPMI 1640 without glucose before APPJ treatment. After a 1 h
      incubation in a cell incubator, cell viability was determined using Cell Counting
      Kit 8. The results showed that, compared to the glucose deprivation group, cells
      treated with APPJ exhibited significantly increased cell viability in a dose
      dependent manner, with 8 s/well observed as an optimal dose. Meanwhile, helium
      flow had no effect on the glucose deprivation-induced cell impairment. Our
      results indicated that APPJ could be potentially used as a treatment method for
      the diseases in the central nervous system related to glucose deprivation. This
      protocol could also be used as a cytoprotective application for other cells with
      different impairments, but the cell culture and APPJ treatment conditions should
      be readjusted, and the treatment dose must be relatively low.

PMID- 29053684
TI  - Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety
      and Tolerability.
AB  - The remotely supervised tDCS (RS-tDCS) protocol enables participation from home
      through guided and monitored self-administration of tDCS treatment while
      maintaining clinical standards. The current consensus regarding the efficacy of
      tDCS is that multiple treatment sessions are needed to observe targeted
      behavioral reductions in symptom burden. However, the requirement for patients to
      travel to clinic daily for stimulation sessions presents a major obstacle for
      potential participants, due to work or family obligations or limited ability to
      travel. This study presents a protocol that directly overcomes these obstacles by
      eliminating the need to travel to clinic for daily sessions. This is an updated
      protocol for remotely supervised self-administration of tDCS for daily treatment
      sessions paired with a program of computer-based cognitive training for use in
      clinical trials. Participants only need to attend clinic twice, for a baseline
      and study-end visit. At baseline, participants are trained and provided with a
      study stimulation device, and a small laptop computer. Participants then complete
      the remainder of their stimulation sessions at home while they are monitored via
      videoconferencing software. Participants complete computerized cognitive
      remediation during stimulation sessions, which may serve a therapeutic role or as
      a "placeholder" for other computer-based activity. Computers are enabled for real
      time monitoring and remote control by study staff. Outcome measures that assess
      feasibility and tolerance are administered remotely with the aid of visual
      analogue scales that are presented onscreen. Following completion of all RS-tDCS
      sessions, participants return to clinic for a study end visit in which all study
      equipment is returned. Results support the safety, feasibility, and scalability
      of the RS-tDCS protocol for use in clinical trials. Across 46 patients, 748 RS
      tDCS sessions have been completed. This protocol serves as a model for use in
      future clinical trials involving tDCS.

PMID- 29053685
TI  - DNA Polymerase Activity Assay Using Near-infrared Fluorescent Labeled DNA
      Visualized by Acrylamide Gel Electrophoresis.
AB  - For any enzyme, robust, quantitative methods are required for characterization of
      both native and engineered enzymes. For DNA polymerases, DNA synthesis can be
      characterized using an in vitro DNA synthesis assay followed by polyacrylamide
      gel electrophoresis. The goal of this assay is to quantify synthesis of both
      natural DNA and modified DNA (M-DNA). These approaches are particularly useful
      for resolving oligonucleotides with single nucleotide resolution, enabling
      observation of individual steps during enzymatic oligonucleotide synthesis. These
      methods have been applied to the evaluation of an array of biochemical and
      biophysical properties such as the measurement of steady-state rate constants of
      individual steps of DNA synthesis, the error rate of DNA synthesis, and DNA
      binding affinity. By using modified components including, but not limited to,
      modified nucleoside triphosphates (NTP), M-DNA, and/or mutant DNA polymerases,
      the relative utility of substrate-DNA polymerase pairs can be effectively
      evaluated. Here, we detail the assay itself, including the changes that must be
      made to accommodate nontraditional primer DNA labeling strategies such as near
      infrared fluorescently labeled DNA. Additionally, we have detailed crucial
      technical steps for acrylamide gel pouring and running, which can often be
      technically challenging.

PMID- 29053686
TI  - Empirical, Metagenomic, and Computational Techniques Illuminate the Mechanisms by
      which Fungicides Compromise Bee Health.
AB  - Growers often use fungicide sprays during bloom to protect crops against disease,
      which exposes bees to fungicide residues. Although considered "bee-safe," there
      is mounting evidence that fungicide residues in pollen are associated with bee
      declines (for both honey and bumble bee species). While the mechanisms remain
      relatively unknown, researchers have speculated that bee-microbe symbioses are
      involved. Microbes play a pivotal role in the preservation and/or processing of
      pollen, which serves as nutrition for larval bees. By altering the microbial
      community, it is likely that fungicides disrupt these microbe-mediated services,
      and thereby compromise bee health. This manuscript describes the protocols used
      to investigate the indirect mechanism(s) by which fungicides may be causing
      colony decline. Cage experiments exposing bees to fungicide-treated flowers have
      already provided the first evidence that fungicides cause profound colony losses
      in a native bumble bee (Bombus impatiens). Using field-relevant doses of
      fungicides, a series of experiments have been developed to provide a finer
      description of microbial community dynamics of fungicide-exposed pollen. Shifts
      in the structural composition of fungal and bacterial assemblages within the
      pollen microbiome are investigated by next-generation sequencing and metagenomic
      analysis. Experiments developed herein have been designed to provide a
      mechanistic understanding of how fungicides affect the microbiome of pollen
      provisions. Ultimately, these findings should shed light on the indirect pathway
      through which fungicides may be causing colony declines.

PMID- 29053687
TI  - Bead Based Multiplex Assay for Analysis of Tear Cytokine Profiles.
AB  - Tear film is a complex mixture of lipids, proteins and minerals which covers the
      external surface of the eye, thereby providing lubrication, nutrition and
      protection to the underlying cells. Analysis of tears is an emerging area for the
      identification of biomarkers for the prediction, diagnosis, and prognosis of
      various ocular diseases. Tears are easily accessible and their collection is non
      invasive. Therefore, advancing technologies are gaining prominence for
      identification of multiple analytes in tears to study changes in protein or
      metabolite composition and its association with pathological conditions. Tear
      cytokines are ideal biomarkers for studying the health of the ocular surface and
      also help in understanding the mechanisms of different ocular surface disorders
      like dry eye disease and vernal conjunctivitis. Bead based multiplex assays have
      the capability of detecting multiple analytes in a small amount of sample with a
      higher sensitivity. Here we describe a standardized protocol of tear sample
      collection, extraction and analysis of cytokine profiling using a bead based
      multiplex assay.

PMID- 29053688
TI  - A Millimeter Scale Flexural Testing System for Measuring the Mechanical
      Properties of Marine Sponge Spicules.
AB  - Many load bearing biological structures (LBBSs)-such as feather rachises and
      spicules-are small (<1 mm) but not microscopic. Measuring the flexural behavior
      of these LBBSs is important for understanding the origins of their remarkable
      mechanical functions. We describe a protocol for performing three-point bending
      tests using a custom-built mechanical testing device that can measure forces
      ranging from 10-5 to 101 N and displacements ranging from 10-7 to 10-2 m. The
      primary advantage of this mechanical testing device is that the force and
      displacement capacities can be easily adjusted for different LBBSs. The device's
      operating principle is similar to that of an atomic force microscope. Namely,
      force is applied to the LBBS by a load point that is attached to the end of a
      cantilever. The load point displacement is measured by a fiber optic displacement
      sensor and converted into a force using the measured cantilever stiffness. The
      device's force range can be adjusted by using cantilevers of different
      stiffnesses. The device's capabilities are demonstrated by performing three-point
      bending tests on the skeletal elements of the marine sponge Euplectella
      aspergillum. The skeletal elements-known as spicules-are silica fibers that are
      approximately 50 um in diameter. We describe the procedures for calibrating the
      mechanical testing device, mounting the spicules on a three-point bending fixture
      with a ~1.3 mm span, and performing a bending test. The force applied to the
      spicule and its deflection at the location of the applied force are measured.

PMID- 29053689
TI  - Whole-cell Currents Induced by Puff Application of GABA in Brain Slices.
AB  - Pharmacological administration is commonly used when conducting whole-cell patch
      clamp recording in brain slices. One of the best methods of drug application
      during electrophysiological recording is the puff technique, which can be used to
      study the effect of pharmacological reagents on neuronal activities in brain
      slices. The greatest advantage of puff application is that the drug concentration
      around the recording site increases rapidly, thus preventing desensitization of
      membrane receptors. Successful use of puff application involves careful attention
      to the following elements: the concentration of the drug, the parameters of the
      puff micropipette, the distance between the tip of a puff micropipette and the
      neuron recorded, and the duration and pressure driving the puff (pounds per
      square inch, psi). This article describes a step-by-step procedure for recording
      whole-cell currents induced by puffing gamma-aminobutyric acid (GABA) onto a
      neuron of a prefrontal cortical slice. Notably, the same procedure can be applied
      with minor modifications to other brain areas such as the hippocampus and the
      striatum, and to different preparations, such as cell cultures.

PMID- 29053690
TI  - 3D Microtissues for Injectable Regenerative Therapy and High-throughput Drug
      Screening.
AB  - To upgrade traditional 2D cell culture to 3D cell culture, we have integrated
      microfabrication with cryogelation technology to produce macroporous microscale
      cryogels (microcryogels), which can be loaded with a variety of cell types to
      form 3D microtissues. Herein, we present the protocol to fabricate versatile 3D
      microtissues and their applications in regenerative therapy and drug screening.
      Size and shape-controllable microcryogels can be fabricated on an array chip,
      which can be harvested off-chip as individual cell-loaded carriers for injectable
      regenerative therapy or be further assembled on-chip into 3D microtissue arrays
      for high-throughput drug screening. Due to the high elastic nature of these
      microscale cryogels, the 3D microtissues exhibit great injectability for
      minimally invasive cell therapy by protecting cells from mechanical shear force
      during injection. This ensures enhanced cell survival and therapeutic effect in
      the mouse limb ischemia model. Meanwhile, assembly of 3D microtissue arrays in a
      standard 384-multi-well format facilitates the use of common laboratory
      facilities and equipment, enabling high-throughput drug screening on this
      versatile 3D cell culture platform.

PMID- 29053691
TI  - Quantitative Whole-mount Immunofluorescence Analysis of Cardiac Progenitor
      Populations in Mouse Embryos.
AB  - The use of ever-advancing imaging techniques has contributed broadly to our
      increased understanding of embryonic development. Pre-implantation development
      and organogenesis are two areas of research that have benefitted greatly from
      these advances, due to the high quality of data that can be obtained directly
      from imaging pre-implantation embryos or ex vivo organs. While pre-implantation
      embryos have yielded data with especially high spatial resolution, later stages
      have been less amenable to three-dimensional reconstruction. Obtaining high
      quality 3D or volumetric data for known embryonic structures in combination with
      fate mapping or genetic lineage tracing will allow for a more comprehensive
      analysis of the morphogenetic events taking place during embryogenesis. This
      protocol describes a whole-mount immunofluorescence approach that allows for the
      labeling, visualization, and quantification of progenitor cell populations within
      the developing cardiac crescent, a key structure formed during heart development.
      The approach is designed in such a way that both cell- and tissue-level
      information can be obtained. Using confocal microscopy and image processing, this
      protocol allows for three-dimensional spatial reconstruction of the cardiac
      crescent, thereby providing the ability to analyze the localization and
      organization of specific progenitor populations during this critical phase of
      heart development. Importantly, the use of reference antibodies allows for
      successive masking of the cardiac crescent and subsequent quantitative
      measurements of areas within the crescent. This protocol will not only enable a
      detailed examination of early heart development, but with adaptations should be
      applicable to most organ systems in the gastrula to early somite stage mouse
      embryo.

PMID- 29053692
TI  - Resonance Fluorescence of an InGaAs Quantum Dot in a Planar Cavity Using
      Orthogonal Excitation and Detection.
AB  - The ability to perform simultaneous resonant excitation and fluorescence
      detection is important for quantum optical measurements of quantum dots (QDs).
      Resonant excitation without fluorescence detection - for example, a differential
      transmission measurement - can determine some properties of the emitting system,
      but does not allow applications or measurements based on the emitted photons. For
      example, the measurement of photon correlations, observation of the Mollow
      triplet, and realization of single photon sources all require collection of the
      fluorescence. Incoherent excitation with fluorescence detection - for example,
      above band-gap excitation - can be used to create single photon sources, but the
      disturbance of the environment due to the excitation reduces the
      indistinguishability of the photons. Single photon sources based on QDs will have
      to be resonantly excited to have high photon indistinguishability, and
      simultaneous collection of the photons will be necessary to make use of them. We
      demonstrate a method to resonantly excite a single QD embedded in a planar cavity
      by coupling the excitation beam into this cavity from the cleaved face of the
      sample while collecting the fluorescence along the sample's surface normal
      direction. By carefully matching the excitation beam to the waveguide mode of the
      cavity, the excitation light can couple into the cavity and interact with the QD.
      The scattered photons can couple to the Fabry-Perot mode of the cavity and escape
      in the surface normal direction. This method allows complete freedom in the
      detection polarization, but the excitation polarization is restricted by the
      propagation direction of the excitation beam. The fluorescence from the wetting
      layer provides a guide to align the collection path with respect to the
      excitation beam. The orthogonality of the excitation and detection modes enables
      resonant excitation of a single QD with negligible laser scattering background.

PMID- 29053693
TI  - In Vivo Tracking of Human Adipose-derived Mesenchymal Stem Cells in a Rat Knee
      Osteoarthritis Model with Fluorescent Lipophilic Membrane Dye.
AB  - In order to support the clinical application of human adipose-derived mesenchymal
      stem cell (haMSC) therapy for knee osteoarthritis (KOA), we examined the efficacy
      of cell persistence and biodistribution of haMSCs in animal models. We
      demonstrated a method to label the cell membrane of haMSCs with lipophilic
      fluorescent dye. Subsequently, intra-articular injection of the labeled cells in
      rats with surgically induced KOA was monitored dynamically by an in vivo imaging
      system. We employed the lipophilic carbocyanines DiD (DilC18 (5)), a far-red
      fluorescent Dil (dialkylcarbocyanines) analog, which utilized a red laser to
      avoid excitation of the natural green autofluorescence from surrounding tissues.
      Furthermore, the red-shifted emission spectra of DiD allowed deep-tissue imaging
      in live animals and the labeling procedure caused no cytotoxic effects or
      functional damage to haMSCs. This approach has been shown to be an efficient
      tracking method for haMSCs in a rat KOA model. The application of this method
      could also be used to determine the optimal administration route and dosage of
      MSCs from other sources in pre-clinical studies.

PMID- 29053694
TI  - Use of a Recombinant Mosquito Densovirus As a Gene Delivery Vector for the
      Functional Analysis of Genes in Mosquito Larvae.
AB  - In vivo microinjection is the most commonly used gene transfer technique for
      analyzing the gene functions in individual mosquitoes. However, this method
      requires a more technically demanding operation and involves complicated
      procedures, especially when used in larvae due to their small size, relatively
      thin and fragile cuticle, and high mortality, which limit its application. In
      contrast, viral vectors for gene delivery have been developed to surmount
      extracellular and intracellular barriers. These systems have the advantages of
      easy manipulation, high gene transduction efficiency, long-term maintenance of
      gene expression, and the ability to produce persistent effects in vivo. Mosquito
      densoviruses (MDVs) are mosquito-specific, small single-stranded DNA viruses that
      can effectively deliver foreign nucleic acids into mosquito cells; however, the
      replacement or insertion of foreign genes to create recombinant viruses typically
      causes a loss of packaging and/or replication abilities, which is a barrier to
      the development of these viruses as delivery vectors. Herein, we report using an
      artificial intronic small-RNA expression strategy to develop a non-defective
      recombinant Aedes aegypti densovirus (AaeDV) in vivo delivery system. Detailed
      procedures for the construction, packaging and quantitative analysis of the
      rAaeDV vectors, and for larval infection are described. This study demonstrates,
      for the first time, the feasibility of developing a non-defective recombinant MDV
      micro RNA (miRNA) expression system, and thus providing a powerful tool for the
      functional analysis of genes in mosquito and establishing a basis for the
      application of viral paratransgenesis for controlling mosquito-borne diseases. We
      demonstrated that Aedes albopictus 1st instar larvae could be easily and
      effectively infected by introducing the virus into the water body of the larvae
      breeding site and that the developed rAaeDVs could be used to overexpress or
      knock down the expression of a specific target gene in larvae, providing a tool
      for the functional analysis of mosquito genes.

PMID- 29053695
TI  - Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant
      Proteins.
AB  - Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located
      on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1
      regulates the activity of PM Orai1 channels in a process known as store operated
      calcium (Ca2+) entry which is the principal Ca2+ signaling process that drives
      the immune response. STIM1 undergoes post-translational N-glycosylation at two
      luminal Asn sites within the Ca2+ sensing domain of the molecule. However, the
      biochemical, biophysical, and structure biological effects of N-glycosylated
      STIM1 were poorly understood until recently due to an inability to readily obtain
      high levels of homogeneous N-glycosylated protein. Here, we describe the
      implementation of an in vitro chemical approach which attaches glucose moieties
      to specific protein sites applicable to understanding the underlying effects of N
      glycosylation on protein structure and mechanism. Using solution nuclear magnetic
      resonance spectroscopy we assess both efficiency of the modification as well as
      the structural consequences of the glucose attachment with a single sample. This
      approach can readily be adapted to study the myriad glycosylated proteins found
      in nature.

PMID- 29053696
TI  - 3' End Sequencing Library Preparation with A-seq2.
AB  - Studies in the last decade have revealed a complex and dynamic variety of pre
      mRNA cleavage and polyadenylation reactions. mRNAs with long 3' untranslated
      regions (UTRs) are generated in differentiated cells whereas proliferating cells
      preferentially express transcripts with short 3'UTRs. We describe the A-seq
      protocol, now at its second version, which was developed to map polyadenylation
      sites genome-wide and study the regulation of pre-mRNA 3' end processing. Also
      this current protocol takes advantage of the polyadenylate (poly(A)) tails that
      are added during the biogenesis of most mammalian mRNAs to enrich for fully
      processed mRNAs. A DNA adaptor with deoxyuracil at its fourth position allows the
      precise processing of mRNA 3' end fragments for sequencing. Not including the
      cell culture and the overnight ligations, the protocol requires about 8 h hands
      on time. Along with it, an easy-to-use software package for the analysis of the
      derived sequencing data is provided. A-seq2 and the associated analysis software
      provide an efficient and reliable solution to the mapping of pre-mRNA 3' ends in
      a wide range of conditions, from 106 or fewer cells.

PMID- 29053697
TI  - Stereotactically-guided Ablation of the Rat Auditory Cortex, and Localization of
      the Lesion in the Brain.
AB  - The rat auditory cortex (AC) is becoming popular among auditory neuroscience
      investigators who are interested in experience-dependence plasticity, auditory
      perceptual processes, and cortical control of sound processing in the subcortical
      auditory nuclei. To address new challenges, a procedure to accurately locate and
      surgically expose the auditory cortex would expedite this research effort.
      Stereotactic neurosurgery is routinely used in pre-clinical research in animal
      models to engraft a needle or electrode at a pre-defined location within the
      auditory cortex. In the following protocol, we use stereotactic methods in a
      novel way. We identify four coordinate points over the surface of the temporal
      bone of the rat to define a window that, once opened, accurately exposes both the
      primary (A1) and secondary (Dorsal and Ventral) cortices of the AC. Using this
      method, we then perform a surgical ablation of the AC. After such a manipulation
      is performed, it is necessary to assess the localization, size, and extension of
      the lesions made in the cortex. Thus, we also describe a method to easily locate
      the AC ablation postmortem using a coordinate map constructed by transferring the
      cytoarchitectural limits of the AC to the surface of the brain.The combination of
      the stereotactically-guided location and ablation of the AC with the localization
      of the injured area in a coordinate map postmortem facilitates the validation of
      information obtained from the animal, and leads to a better analysis and
      comprehension of the data.

PMID- 29053698
TI  - Simultaneous Multi-surface Anodizations and Stair-like Reverse Biases Detachment
      of Anodic Aluminum Oxides in Sulfuric and Oxalic Acid Electrolyte.
AB  - After reporting on the two-step anodization, nanoporous anodic aluminum oxides
      (AAOs) have been widely utilized in the versatile fields of fundamental sciences
      and industrial applications owing to their periodic arrangement of nanopores with
      relatively high aspect ratio. However, the techniques reported so far, which
      could be only valid for mono-surface anodization, show critical disadvantages,
      i.e., time-consuming as well as complicated procedures, requiring toxic
      chemicals, and wasting valuable natural resources. In this paper, we demonstrate
      a facile, efficient, and environmentally clean method to fabricate nanoporous
      AAOs in sulfuric and oxalic acid electrolytes, which can overcome the limitations
      that result from conventional AAO fabricating methods. First, plural AAOs are
      produced at one time through simultaneous multi-surfaces anodization (SMSA),
      indicating mass-producibility of the AAOs with comparable qualities. Second,
      those AAOs can be separated from the aluminum (Al) substrate by applying stair
      like reverse biases (SRBs) in the same electrolyte used for the SMSAs, implying
      simplicity and green technological characteristics. Finally, a unit sequence
      consisting of the SMSAs sequentially combined with SRBs-based detachment can be
      applied repeatedly to the same Al substrate, which reinforces the advantages of
      this strategy and also guarantees the efficient usage of natural resources.

PMID- 29053699
TI  - Evaluation of Synapse Density in Hippocampal Rodent Brain Slices.
AB  - In the brain, synapses are specialized junctions between neurons, determining the
      strength and spread of neuronal signaling. The number of synapses is tightly
      regulated during development and neuronal maturation. Importantly, deficits in
      synapse number can lead to cognitive dysfunction. Therefore, the evaluation of
      synapse number is an integral part of neurobiology. However, as synapses are
      small and highly compact in the intact brain, the assessment of absolute number
      is challenging. This protocol describes a method to easily identify and evaluate
      synapses in hippocampal rodent slices using immunofluorescence microscopy. It
      includes a three-step procedure to evaluate synapses in high-quality confocal
      microscopy images by analyzing the co-localization of pre- and postsynaptic
      proteins in hippocampal slices. It also explains how the analysis is performed
      and gives representative examples from both excitatory and inhibitory synapses.
      This protocol provides a solid foundation for the analysis of synapses and can be
      applied to any research investigating the structure and function of the brain.

PMID- 29053700
TI  - Come to the Light Side: In Vivo Monitoring of Pseudomonas aeruginosa Biofilm
      Infections in Chronic Wounds in a Diabetic Hairless Murine Model.
AB  - The presence of bacteria as structured biofilms in chronic wounds, especially in
      diabetic patients, is thought to prevent wound healing and resolution. Chronic
      mouse wounds models have been used to understand the underlying interactions
      between the microorganisms and the host. The models developed to date rely on the
      use of haired animals and terminal collection of wound tissue for determination
      of viable bacteria. While significant insight has been gained with these models,
      this experimental procedure requires a large number of animals and sampling is
      time consuming. We have developed a novel murine model that incorporates several
      optimal innovations to evaluate biofilm progression in chronic wounds: a) it
      utilizes hairless mice, eliminating the need for hair removal; b) applies pre
      formed biofilms to the wounds allowing for the immediate evaluation of
      persistence and effect of these communities on host; c) monitors biofilm
      progression by quantifying light production by a genetically engineered
      bioluminescent strain of Pseudomonas aeruginosa, allowing real-time monitoring of
      the infection thus reducing the number of animals required per study. In this
      model, a single full-depth wound is produced on the back of STZ-induced diabetic
      hairless mice and inoculated with biofilms of the P. aeruginosa bioluminescent
      strain Xen 41. Light output from the wounds is recorded daily in an in vivo
      imaging system, allowing for in vivo and in situ rapid biofilm visualization and
      localization of biofilm bacteria within the wounds. This novel method is flexible
      as it can be used to study other microorganisms, including genetically engineered
      species and multi-species biofilms, and may be of special value in testing anti
      biofilm strategies including antimicrobial occlusive dressings.

PMID- 29053701
TI  - Marshall Klaus: the impact of a pioneer in neonatology.

PMID- 29053702
TI  - The effects of adding prophylactic phenobarbital to therapeutic hypothermia in
      the term-equivalent hypoxic-ischemic rat.
AB  - BackgroundHypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal
      morbidity and mortality. Therapeutic hypothermia (TH) is the only available
      intervention, but neuroprotection is incomplete and variable. Seizures are common
      in infants with HIE undergoing TH and may worsen outcome. Phenobarbital (PB) is
      sometimes added, although use of prophylactic PB is controversial in the neonate.
      We hypothesize that prophylactic PB will not reduce, and may enhance, the
      neuroprotective effects of TH on brain injury and motor outcomes in the postnatal
      day 10 (P10) hypoxic-ischemic (HI) rat.MethodsP10 rat pups were subjected to
      unilateral HI and 4 h recovery with: normothermia (N); hypothermia (TH); and
      hypothermia with phenobarbital (TH+PB). Brain damage was assessed longitudinally
      at 24 h and 2 weeks using brain magnetic resonance imaging and 12 weeks using
      histochemical analysis. Motor function was assessed with the beam walk and
      cylinder tests.ResultsTH and TH+PB induced neuroprotection, as measured by global
      brain damage score and improved motor function. Exploratory analyses suggest that
      TH+PB may confer enhanced protection, especially to the extent of
      damage.ConclusionProphylactic PB with TH is not deleterious and may provide
      additional long-term neuroprotection, including improvement of motor outcomes
      following HI in the term-equivalent, neonatal rat.

PMID- 29053703
TI  - Development of severe bronchopulmonary dysplasia is associated with alterations
      in fecal volatile organic compounds.
AB  - BackgroundThe aim of this study was to evaluate the potential of fecal volatile
      organic compounds (VOCs), obtained by means of an electronic nose device
      (Cyranose 320), as early non-invasive biomarker for BPD.MethodsIn this nested
      case-control study performed at three Neonatal Intensive Care Units, fecal
      samples obtained at postnatal age of 7, 14, 21, and 28 days from preterm infants
      with severe bronchopulmonary dysplasia (BPD) were compared with fecal VOC
      profiles from matched controls. Microbiota analysis was performed by means of IS
      pro technique on fecal samples collected at 28 days postnatally.ResultsVOC
      profiles of infants developing severe BPD (n=15) could be discriminated from
      matched controls (n=15) at postnatal age of 14 days (area under the curve (+/-95%
      confidence interval), P-value, sensitivity, specificity; 0.72 (0.54-0.90), 0.040,
      60.0%, 73.3%), 21 days (0.71 (0.52-0.90), 0.049, 66.7%, 73.3%) and 28 days (0.77
      (0.59-0.96), 0.017, 69.2%, 69.2%) but not at 7 days. Intestinal microbiota did
      not differ between BPD subjects and controls.ConclusionFecal VOC profiles of
      infants developing BPD could be differentiated from controls at postnatal day 14,
      21, and 28. VOC differences could not be directed to intestinal microbiota
      alterations but presumably reflect local and systemic metabolic and inflammatory
      pathways associated with BPD.

PMID- 29053704
TI  - Hypoxic renal injury in newborns with abdominal compartment syndrome (clinical
      and experimental study).
AB  - BackgroundSurgical treatment for gastroschisis and congenital diaphragmatic
      hernia (CDH) commonly leads to abdominal compartment syndrome (ACS) associated
      with hypoxic renal injury. We hypothesized that measurement of urinary and serum
      concentrations of vascular endothelial growth factor (VEGF), pi-glutathione S
      transferase (pi-GST), and monocyte chemoattractant protein-1 (MCP-1) may serve
      for noninvasive detection of hypoxic renal injury in such patients.MethodsIntra
      abdominal pressure (IAP), renal excretory function, and the biomarker levels were
      analyzed before, 4, and 10 days after surgery. Association between the biomarker
      levels and renal histology was investigated using an original model of ACS in
      newborn rats.ResultsFour days after surgery, IAP increased, renal excretory
      function decreased, and the levels of VEGF, pi-GST, and MCP-1 increased,
      indicating renal injury. Ten days after surgery, IAP partially decreased, renal
      excretory function completely restored, but the biomarker levels remained
      elevated, suggesting the ongoing kidney injury. In the model of ACS, increase in
      the biomarker levels was associated with progressing kidney morphological
      alteration.ConclusionSurgical treatment for gastroschisis and CDH is associated
      with prolonged hypoxic kidney injury despite complete restoration of renal
      excretory function. Follow-up measurement of VEGF, pi-GST, and MCP-1 levels may
      provide a better tool for noninvasive assessment of renal parenchyma in newborns
      with ACS.

PMID- 29053705
TI  - Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in
      the brainstem of neonates.
AB  - BackgroundVagus nerve stimulation (VNS) is an Food and Drug Administration
      approved method delivering electrical impulses for treatment of depression and
      epilepsy in adults. The vagus nerve innervates the majority of visceral organs
      and cervix, but potential impacts of VNS on the progress of pregnancy and the
      fetus are not well studied.MethodsWe tested the hypothesis that VNS in pregnant
      dams does not induce inflammatory changes in the cardio-respiratory control
      regions of the pups' brainstem, potentially impacting the morbidity and mortality
      of offspring. Pregnant dams were implanted with stimulators providing
      intermittent low or high frequency electrical stimulation of the sub
      diaphragmatic esophageal segment of the vagus nerve for 6-7 days until delivery.
      After birth, we collected pup brainstems that included cardio-respiratory control
      regions and counted the cells labeled for pro-inflammatory cytokines (interleukin
      (IL)-1beta, IL-6, tumor necrosis factor-alpha) and high mobility group box
      1.ResultsNeither pup viability nor number of cells labeled for pro-inflammatory
      cytokines in nucleus tractus solitarii or hypoglossal motor nucleus was impaired
      by VNS. We provide evidence suggesting that chronic VNS of pregnant mothers does
      not impede the progress or outcome of pregnancy.ConclusionVNS does not cause
      preterm birth, affect well-being of progeny, or impact central inflammatory
      processes that are critical for normal cardiovascular and respiratory function in
      newborns.

PMID- 29053706
TI  - Solea senegalensis sperm cryopreservation: New insights on sperm quality.
AB  - Cryopreservation of Senegalese sole sperm can represent an alternative to
      overcome some reproductive problems of this species. However, it is important to
      guarantee the safe use of cryopreserved sperm by selecting an appropriate
      protocol according to a high demand quality need to be ensured. It has been
      demonstrated that traditional assays such as motility and viability do not
      provide enough information to identify specific damage caused by cryopreservation
      process (freezing and thawing). Specific tests, including lipid peroxidation and
      DNA damage, should be performed. In the present study, motility and lipid
      peroxidation were performed as specific tests allowing us to discard
      cryopreservation conditions such as methanol as internal cryoprotectant and
      bovine serum albumin as external cryoprotectant. In addition, a caspase 3/7
      detection by flow cytometry was performed to analyze apoptosis activity in the
      best selected conditions. Moreover, new highly sensitive tests based on
      transcript number detection have recently been described in fish sperm
      cryopreservation. For this reason, a transcript level detection assay was
      performed on certain oxidative and chaperone genes related to fertilization
      ability and embryo development (hsp70, hsp90BB, hsp90AA, gpx) to select the best
      cryopreservation conditions. DMSO+ egg yolk proved to be the best cryoprotectant
      combination in terms of transcript level. This study describes an optimized
      cryopreservation protocol for Solea senegalensis sperm demonstrating for the
      first time that transcript degradation is the most sensitive predictor of cell
      status in this species after cryopreservation.

PMID- 29053707
TI  - High glucose augments angiotensinogen in human renal proximal tubular cells
      through hepatocyte nuclear factor-5.
AB  - High glucose has been demonstrated to induce angiotensinogen (AGT) synthesis in
      the renal proximal tubular cells (RPTCs) of rats, which may further activate the
      intrarenal renin-angiotensin system (RAS) and contribute to diabetic nephropathy.
      This study aimed to investigate the effects of high glucose on AGT in the RPTCs
      of human origin and identify the glucose-responsive transcriptional factor(s)
      that bind(s) to the DNA sequences of AGT promoter in human RPTCs. Human kidney
      (HK)-2 cells were treated with normal glucose (5.5 mM) and high glucose (15.0
      mM), respectively. Levels of AGT mRNA and AGT secretion of HK-2 cells were
      measured by real-time polymerase chain reaction (PCR) and enzyme-linked
      immunosorbent assay (ELISA), respectively. Consecutive 5'-end deletion mutant
      constructs and different site-directed mutagenesis products of human AGT promoter
      sequences were respectively transfected into HK-2 cells, followed by AGT promoter
      activity measurement through dual luciferase assay. High glucose significantly
      augmented the levels of AGT mRNA and AGT secretion of HK-2 cells, compared with
      normal glucose treatment. High glucose also significantly augmented AGT promoter
      activity in HK-2 cells transfected with the constructs of human AGT promoter
      sequences, compared with normal glucose treatment. Hepatocyte nuclear factor
      (HNF)-5 was found to be one of the glucose-responsive transcriptional factors of
      AGT in human RPTCs, since the mutation of its binding sites within AGT promoter
      sequences abolished the above effects of high glucose on AGT promoter activity as
      well as levels of AGT mRNA and its secretion. The present study has demonstrated,
      for the first time, that high glucose augments AGT in human RPTCs through HNF-5,
      which provides a potential therapeutic target for diabetic nephropathy.

PMID- 29053708
TI  - Ssn6-Tup1 global transcriptional co-repressor: Role of the N-terminal glutamine
      rich region of Ssn6.
AB  - The Ssn6-Tup1 complex is a general transcriptional co-repressor formed by the
      interaction of Ssn6, a tetratricopeptide repeat (TPR) protein, with the Tup1
      repressor. We have previously shown that the N-terminal domain of Ssn6 comprising
      TPRs 1 to 3 is necessary and sufficient for this interaction and that TPR1 plays
      critical role. In a subsequent study, we provided evidence that in the absence of
      Tup1, TPR1 is susceptible to proteolysis and that conformational change(s)
      accompany the Ssn6-Tup1 complex formation. In this study, we address the question
      whether the N-terminal non-TPR, glutamine-rich tail of Ssn6 (NTpolyQ), plays any
      role in the Ssn6/Tup1 association. Our biochemical and yeast-two-hybrid data show
      that truncation/deletion of the NTpolyQ domain of Ssn6 results in its self
      association and prevents Tup1 interaction. These results combined with in silico
      modeling data imply a major role of the NTpolyQ tail of Ssn6 in regulating its
      interaction with Tup1.

PMID- 29053709
TI  - Changes in utilization and peri-operative outcomes of bariatric surgery in large
      U.S. hospital database, 2011-2014.
AB  - BACKGROUND: With the epidemic of morbid obesity, bariatric surgery has been
      accepted as one of the most effective treatments of obesity. OBJECTIVE: To
      investigate recent changes in the utilization of bariatric surgery, patients and
      hospital characteristics, and in-hospital complications in a nationwide hospital
      database in the United States. SETTING: This is a secondary data analysis of the
      Premier Perspective database. METHODS: ICD-9 codes were used to identify
      bariatric surgeries performed between 2011 and 2014. Descriptive statistics were
      computed and regression was used. RESULTS: A total of 74,774 bariatric procedures
      were identified from 436 hospitals between 2011 and 2014. During this time
      period, the proportion of gastric bypass (from 44.8% to 31.3%; P for trend <
      0.0001) and gastric banding (from 22.8% to 5.2%; P for trend < 0.0001) decreased,
      while the proportion of sleeve gastrectomy (from 13.7% to 56.9%; P for trend <
      0.0001) increased substantially. The proportion of bariatric surgery performed
      for outpatients decreased from 17.15% in 2011 to 8.11% in 2014 (P for trend <
      0.0001). The majority of patients undergoing surgery were female (78.5%), white
      (65.6%), younger than 65 years (93.8%), and insured with managed care (53.6%). In
      hospital mortality rate and length of hospital stay remained stable. The majority
      of surgeries were performed in high-volume (71.8%) and urban (91.6%) hospitals.
      CONCLUSIONS: Results based on our study sample indicated that the popularity of
      various bariatric surgery procedures changed significantly from 2011 to 2014.
      While the rates of in-hospital complications were stable, disparities in the use
      of bariatric surgery regarding gender, race, and insurance still exist.

PMID- 29053710
TI  - Early Levallois and the beginning of the Middle Paleolithic in central Italy.
AB  - In the second half of the 19th century Pleistocene faunas were discovered in two
      sites, Sedia del Diavolo and Monte delle Gioie, contained in deposits of the
      Aniene River in the area of Rome (Latium, Italy). Fieldwork by A.C. Blanc in the
      late 1930's proved the association of fauna and lithic industry within fluvial
      deposits interbedded with volcanoclastic layers. A human femoral diaphysis and a
      metatarsal were later identified in the faunal assemblage from Sedia del Diavolo
      and evaluated as Neandertal. The lithic assemblages from these two sites were the
      basis of the definition of the Protopontinian by M. Taschini, which she viewed as
      a late Middle Pleistocene industry very similar to the later, Upper Pleistocene
      Pontinian industries, thought to be characteristic of the Latium Mousterian. The
      chronostratigraphic framework of the Aniene river deposits has been recently
      updated and the lithic assemblages from these two sites are now confidently dated
      between 295 and 290 ka, close to the transition from MIS 9 to MIS 8. They fit
      chronologically between the industries of layers m and d from Torre in Pietra, a
      site 26 km northwest of Rome. The presence of the Levallois debitage is
      indisputable yet it occurs within an original technical context, different from
      what is known in other early occurrences of the Levallois. The date confirms the
      proposed chronology for the early Levallois in Europe. More importantly these two
      assemblages demonstrate that this technology can emerge in more diversified
      contexts than usually described. This suggests that its dispersal in Europe may
      have been rapid.

PMID- 29053711
TI  - Evaluation of spoligotyping, SNPs and customised MIRU-VNTR combination for
      genotyping Mycobacterium tuberculosis clinical isolates in Madagascar.
AB  - BACKGROUND: Combining different molecular typing methods for Mycobacterium
      tuberculosis complex (MTBC) can be a powerful tool for molecular epidemiology
      based investigation of TB. However, the current standard method that provides
      high discriminatory power for such a combination, mycobacterial interspersed
      repetitive units-variable numbers of tandem repeats typing (MIRU-VNTR), is
      laborious, time-consuming and often too costly for many resource-limited
      laboratories. We aimed to evaluate a reduced set of loci for MIRU-VNTR typing in
      combination with spoligotyping and SNP-typing for routine molecular epidemiology
      of TB. METHOD: Spoligotyping and SNP-typing, in combination with the 15 loci MIRU
      VNTR typing, were first used to type clinical MTBC isolates (n = 158) from
      Madagascar. A step by step reduction of MIRU-VNTR loci number was then performed
      according to the Hunter and Gaston Discriminatory Index (HGDI) and to the
      Principal component analysis (PCA) correlation with the spoligotype profiles to
      evaluate the discrimination power inside the generated spoligotype clusters. The
      15 MIRU-VNTR was used as reference and SNP-typing was used to determine the main
      MTBC lineages. RESULTS: Of the 158 clinical isolates studied, the SNP-typing
      classified 23 into Lineage 1 (14.6%), 31 into Lineage 2 (19.6%), 23 into Lineage
      3 (14.6%) and 81 into Lineage 4 strains (51.3%). 37 different spoligotypes
      profiles were obtained, 15 of which were unique and 20 in clusters. 15-loci MIRU
      VNTR typing revealed 144 different genotypes: 132 isolates had a unique MIRU-VNTR
      profile and 27 isolates were grouped into 12 clusters. After a stepwise reduction
      of the MIRU-VNTR loci number within each main spoligotype families, three
      different sets composed of 5 customised MIRU-VNTR loci had a similar
      discrimination level to the reference 15 loci MIRU-VNTR in lineage 1, lineage 2
      and lineage 3. For lineage 4, a set of 4 and 3 MIRU-VNTR loci were proposed to
      subtype the Harleem and LAM spoligotype families, respectively. For the T
      spoligotype family, a set of 5 MIRU-VNTR loci was proposed. CONCLUSION: According
      to the lineages and the spoligotype families, the number of MIRU-VNTR loci can be
      reduced to get an optimal classification of MTBC. These customized sets of MIRU
      VNTR loci reduce workload and save resources while maintaining optimal
      discriminatory power.

PMID- 29053712
TI  - Reproductive desire among women living with HIV/AIDS in Central Brazil:
      Prevalence and associated factors.
AB  - BACKGROUND: The purpose of this study was to estimate the prevalence and examine
      the factors associated with reproductive desire among women living with HIV/AIDS
      (WLWHA) in Central Brazil. METHODS: A cross-sectional study involving 274 WLWHA,
      aged 18 to 49 years, was conducted with the support of treatment services and non
      governmental organizations that assist people living with HIV/AIDS. Data
      regarding sociodemographic characteristics, substance use, sexual behavior, and
      reproductive variables were collected through interviews. Poisson regression with
      robust variance was used to analyze the factors associated with reproductive
      desire. RESULTS: The prevalence of reproductive desire was 25.9% (95.0%
      confidence interval [CI]: 21.1-31.4%). This outcome was associated with age < 30
      years (adjusted prevalence ratio [APR]: 2.93; p < 0.001), black skin color or
      race (APR: 2.28; p = 0.017), partner's reproductive desire (APR: 7.55; p <
      0.001), absence of children (APR: 2.13; p = 0.003), history of abortion (APR:
      1.65; p = 0.045) and undetectable viral load at the time of data collection (APR:
      1.92; p = 0.043). CONCLUSION: The prevalence of reproductive desire among WLWHA
      was relatively high. It is necessary to include fertility issues as part of
      assistance and counseling for women in referral services to support them with
      their feelings, goals, and needs regarding reproductive choices.

PMID- 29053713
TI  - A longitudinal study of facial growth of Southern Chinese in Hong Kong:
      Comprehensive photogrammetric analyses.
AB  - INTRODUCTION: Existing studies on facial growth were mostly cross-sectional in
      nature and only a limited number of facial measurements were investigated. The
      purposes of this study were to longitudinally investigate facial growth of
      Chinese in Hong Kong from 12 through 15 to 18 years of age and to compare the
      magnitude of growth changes between genders. METHODS AND FINDINGS: Standardized
      frontal and lateral facial photographs were taken from 266 (149 females and 117
      males) and 265 (145 females and 120 males) participants, respectively, at all
      three age levels. Linear and angular measurements, profile inclinations, and
      proportion indices were recorded. Statistical analyses were performed to
      investigate growth changes of facial features. Comparisons were made between
      genders in terms of the magnitude of growth changes from ages 12 to 15, 15 to 18,
      and 12 to 18 years. For the overall face, all linear measurements increased
      significantly (p < 0.05) except for height of the lower profile in females (p =
      0.069) and width of the face in males (p = 0.648). In both genders, the increase
      in height of eye fissure was around 10% (p < 0.001). There was significant
      decrease in nasofrontal angle (p < 0.001) and increase in nasofacial angle (p <
      0.001) in both genders and these changes were larger in males. Vermilion-total
      upper lip height index remained stable in females (p = 0.770) but increased in
      males (p = 0.020). Nasofrontal angle (effect size: 0.55) and lower vermilion
      contour index (effect size: 0.59) demonstrated large magnitude of gender
      difference in the amount of growth changes from 12 to 18 years. CONCLUSIONS:
      Growth changes of facial features and gender differences in the magnitude of
      facial growth were determined. The findings may benefit different clinical
      specialties and other nonclinical fields where facial growth are of interest.

PMID- 29053715
TI  - A robust ECC based mutual authentication protocol with anonymity for session
      initiation protocol.
AB  - Over the past few years, Session Initiation Protocol (SIP) is found as a
      substantial application-layer protocol for the multimedia services. It is
      extensively used for managing, altering, terminating and distributing the
      multimedia sessions. Authentication plays a pivotal role in SIP environment.
      Currently, Lu et al. presented an authentication protocol for SIP and profess
      that newly proposed protocol is protected against all the familiar attacks.
      However, the detailed analysis describes that the Lu et al.'s protocol is exposed
      against server masquerading attack and user's masquerading attack. Moreover, it
      also fails to protect the user's identity as well as it possesses incorrect login
      and authentication phase. In order to establish a suitable and efficient
      protocol, having ability to overcome all these discrepancies, a robust ECC-based
      novel mutual authentication mechanism with anonymity for SIP is presented in this
      manuscript. The improved protocol contains an explicit parameter for user to cope
      the issues of security and correctness and is found to be more secure and
      relatively effective to protect the user's privacy, user's masquerading and
      server masquerading as it is verified through the comprehensive formal and
      informal security analysis.

PMID- 29053714
TI  - Atopic asthmatic immune phenotypes associated with airway microbiota and airway
      obstruction.
AB  - BACKGROUND: Differences in asthma severity may be related to inflammation in the
      airways. The lower airway microbiota has been associated with clinical features
      such as airway obstruction, symptom control, and response to corticosteroids.
      OBJECTIVE: To assess the relationship between local airway inflammation, severity
      of disease, and the lower airway microbiota in atopic asthmatics. METHODS: A
      cohort of young adult, atopic asthmatics with intermittent or mild/moderate
      persistent symptoms (n = 13) were assessed via bronchoscopy, lavage, and
      spirometry. These individuals were compared to age matched non-asthmatic controls
      (n = 6) and to themselves after six weeks of treatment with fluticasone
      propionate (FP). Inflammation of the airways was assessed via a cytokine and
      chemokine panel. Lower airway microbiota composition was determined by
      metagenomic shotgun sequencing. RESULTS: Unsupervised clustering of cytokines and
      chemokines prior to treatment with FP identified two asthmatic phenotypes (AP),
      termed AP1 and AP2, with distinct bronchoalveolar lavage inflammatory profiles.
      AP2 was associated with more obstruction, compared to AP1. After treatment with
      FP reduced MIP-1beta and TNF-alpha and increased IL-2 was observed. A module of
      highly correlated cytokines that include MIP-1beta and TNF-alpha was identified
      that negatively correlated with pulmonary function. Independently, IL-2 was
      positively correlated with pulmonary function. The airway microbiome composition
      correlated with asthmatic phenotypes. AP2, prior to FP treatment, was enriched
      with Streptococcus pneumoniae. Unique associations between IL-2 or the cytokine
      module and the microbiota composition of the airways were observed in asthmatics
      subjects prior to treatment but not after or in controls. CONCLUSION: The
      underlying inflammation in atopic asthma is related to the composition of
      microbiota and is associated with severity of airway obstruction. Treatment with
      inhaled corticosteroids was associated with changes in the airway inflammatory
      response to microbiota.

PMID- 29053716
TI  - QTL controlling grain filling under terminal drought stress in a set of wild
      barley introgression lines.
AB  - Drought is a major abiotic stress impeding the yield of cereal crops globally.
      Particularly in Mediterranean environments, water becomes a limiting factor
      during the reproductive developmental stage, causing yield losses. The wild
      progenitor of cultivated barley Hordeum vulgare ssp spontaneum (Hsp) is a
      potentially useful source of drought tolerance alleles. Wild barley introgression
      lines like the S42IL library may facilitate the introduction of favorable exotic
      alleles into breeding material. The complete set of 83 S42ILs was genotyped with
      the barley 9k iSelect platform in order to complete genetic information obtained
      in previous studies. The new map comprises 2,487 SNPs, spanning 989.8 cM and
      covering 94.5% of the Hsp genome. Extent and positions of introgressions were
      confirmed and new information for ten additional S42ILs was collected. A subset
      of 49 S42ILs was evaluated for drought response in four greenhouse experiments.
      Plants were grown under well-watered conditions until ten days post anthesis.
      Subsequently drought treatment was applied by reducing the available water.
      Several morphological and harvest parameters were evaluated. Under drought
      treatment, trait performance was reduced. However, there was no interaction
      effect between genotype and treatment, indicating that genotypes, which performed
      best under control treatment, also performed best under drought treatment. In
      total, 40 QTL for seven traits were detected in this study. For instance,
      favorable Hsp effects were found for thousand grain weight (TGW) and number of
      grains per ear under drought stress. In particular, line S42IL-121 is a promising
      candidate for breeding improved malting cultivars, displaying a TGW, which was
      increased by 17% under terminal drought stress due to the presence of an unknown
      wild barley QTL allele on chromosome 4H. The introgression line showed a similar
      advantage in previous field experiments and in greenhouse experiments under early
      drought stress. We, thus, recommend using S42IL-121 in barley breeding programs
      to enhance terminal drought tolerance.

PMID- 29053717
TI  - GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and
      hormonal secretions in the rodent.
AB  - GPR40 agonists are effective antidiabetic agents believed to lower glucose
      through direct effects on the beta cell to increase glucose stimulated insulin
      secretion. However, not all GPR40 agonists are the same. Partial agonists lower
      glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may
      incorporate additional therapeutic effects through increases in insulinotrophic
      incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both
      insulin and incretin secretion in vivo over time in diabetic GK rats. We also
      describe effects of AgoPAMs in vivo to lower glucose and body weight beyond what
      is seen with partial GPR40 agonists in both the acute and chronic setting.
      Further comparisons of the glucose lowering profile of AgoPAMs suggest these
      compounds may possess greater glucose control even in the presence of elevated
      glucagon secretion, an unexpected feature observed with both acute and chronic
      treatment with AgoPAMs. Together these studies highlight the complexity of GPR40
      pharmacology and the potential additional benefits AgoPAMs may possess above
      partial agonists for the diabetic patient.

PMID- 29053718
TI  - Optical coherence tomography angiography vessel density in children with type 1
      diabetes.
AB  - PURPOSE: To assess the optical coherence tomography angiography (OCTA) retinal
      vessel density and foveal avascular zone (FAZ) in children with type 1 diabetes
      (T1D) and compare potential pathologic early changes in this population to
      healthy age-matched controls. METHODS: This study included 130 pubescent
      children: 94 with T1D (188 eyes) and 36 of their age-matched control group (60
      eyes). OCTA was performed using AngioVue (Avanti, Optivue). FAZ area (mm2) in
      superficial plexus, whole superficial capillary vessel density (wsVD), fovea
      superficial vessel density (fsVD), parafovea superficial vessel density (psVD),
      whole deep vessel density (wdVD), fovea deep vessel density (fdVD), parafovea
      deep vessel density (pdVD), foveal thickness (FT) (MUm) and parafoveal thickness
      (PFT) (MUm) were taken into analysis. Among the studied patients with T1D there
      were assessed codependences regarding the investigated foveal and parafoveal
      parameters and selected potential predictors, i.e. patient's age (years),
      diabetes duration time (years), age of onset of the disease (years), mean level
      of glycated hemoglobin (HbA1C) (%), and concentration of serum creatinine
      (mg/dL). RESULTS: None of the abovementioned OCT and OCTA parameters was
      statistically significantly different between the groups. The patient's age
      statistically significantly did not influent any of the OCT and OCTA parameters.
      Yet an elevated level of HbA1C tended to reduce the parafovea superficial vessel
      density (p = 0.039), and parafoveal thickness (p = 0.003) and an increased serum
      creatinine level correlated with the decreased whole deep vessel density (p <
      0.001). The parafovea deep vessel density in the diabetic patients decreased when
      the serum creatinine level (p = 0.008), age of onset of the disease (p = 0.028),
      and diabetes duration time (p = 0.014) rose. CONCLUSIONS: Vessel density, both in
      superficial and deep plexuses, and FAZ area are normal in pubescent children with
      T1D comparing to healthy subjects. An elevated level of HbA1C correlated with
      reduced psVD and PFT. Longitudinal observation of these young patients is needed
      to determine if any of these OCTA measurements are predictive of future DR
      severity.

PMID- 29053719
TI  - Total disc replacement using tissue-engineered intervertebral discs in the canine
      cervical spine.
AB  - The most common reason that adults in the United States see their physician is
      lower back or neck pain secondary to degenerative disc disease. To date,
      approaches to treat degenerative disc disease are confined to purely mechanical
      devices designed to either eliminate or enable flexibility of the diseased motion
      segment. Tissue engineered intervertebral discs (TE-IVDs) have been proposed as
      an alternative approach and have shown promise in replacing native IVD in the
      rodent tail spine. Here we demonstrate the efficacy of our TE-IVDs in the canine
      cervical spine. TE-IVD components were constructed using adult canine annulus
      fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels,
      respectively. Seeded gels were formed into a single disc unit using molds
      designed from the geometry of the canine spine. Skeletally mature beagles
      underwent discectomy with whole IVD resection at levels between C3/4 and C6/7,
      and were then divided into two groups that received only discectomy or discectomy
      followed by implantation of TE-IVD. Stably implanted TE-IVDs demonstrated
      significant retention of disc height and physiological hydration compared to
      discectomy control. Both 4-week and 16-week histological assessments demonstrated
      chondrocytic cells surrounded by proteoglycan-rich matrices in the NP and by
      fibrocartilaginous matrices in the AF portions of implanted TE-IVDs. Integration
      into host tissue was confirmed over 16 weeks without any signs of immune
      reaction. Despite the significant biomechanical demands of the beagle cervical
      spine, our stably implanted TE-IVDs maintained their position, structure and
      hydration as well as disc height over 16 weeks in vivo.

PMID- 29053720
TI  - Vocalizations of adult male Asian koels (Eudynamys scolopacea) in the breeding
      season.
AB  - Defining the vocal repertoire provides a basis for understanding the role of
      acoustic signals in sexual and social interactions of an animal. The Asian koel
      (Eudynamys scolopacea) is a migratory bird which spends its summer breeding
      season in the plains of Pakistan. The bird is typically wary and secretive but
      produces loud and distinct calls, making it easily detected when unseen. Like the
      other birds in the wild, presumably Asian koels use their calls for social
      cohesion and coordination of different behaviors. To date, the description of
      vocal repertoire of the male Asian koel has been lacking. Presently we analyzed
      and described for the first time the vocalizations of the adult male Asian koel,
      recorded in two consecutive breeding seasons. Using 10 call parameters, we
      categorized the vocalization type into six different categories on the basis of
      spectrogram and statistical analyses, namely the; "type 1 cooee call", "type 2
      cooee call", "type 1 coegh call", "type 2 coegh call", "wurroo call" and "coe
      call". These names were assigned not on the basis of functional analysis and were
      therefore onomatopoeic. Stepwise cross validated discriminant function analysis
      classified the vocalization correctly (100%) into the predicted vocal categories
      that we initially classified on the basis of spectrographic examination. Our
      findings enrich the biological knowledge about vocalizations of the adult male
      Asian koel and provide a foundation for future acoustic monitoring of the
      species, as well as for comparative studies with vocalizations of other bird
      species of the cuckoo family. Further studies on the vocalizations of the Asian
      koel are required to unravel their functions in sexual selection and individual
      recognition.

PMID- 29053722
TI  - Impact of water-deficit stress on tritrophic interactions in a wheat-aphid
      parasitoid system.
AB  - Increasing temperature and CO2 concentrations can alter tritrophic interactions
      in ecosystems, but the impact of increasingly severe drought on such interactions
      is not well understood. We examined the response of a wheat-aphid-parasitoid
      system to variation in water-deficit stress levels. Our results showed that arid
      area clones of the aphid, Sitobion avenae (Fabricius), tended to have longer
      developmental times compared to semiarid and moist area clones, and the
      development of S. avenae clones tended to be slower with increasing levels of
      water-deficit. Body sizes of S. avenae clones from all areas decreased with
      increasing water-deficit levels, indicating their declining adaptation potential
      under drought. Compared to arid area clones, moist area clones of S. avenae had a
      higher frequency of backing under severe water stress only, but a higher
      frequency of kicking under well-watered conditions only, suggesting a water
      deficit level dependent pattern of resistance against the parasitoid, Aphidius
      gifuensis (Ashmead). The number of S. avenae individuals attacked by the
      parasitoid in 10 min showed a tendency to decrease with increasing water-deficit
      levels. Clones of S. avenae tended to have lower parasitism rates under
      treatments with higher water-deficit levels. The development of the parasitoid
      tended to be slower under higher levels of water-deficit stress. Thus, the bottom
      up effects of water-deficit stressed plants were negative on S. avenae. However,
      the top-down effects via parasitoids were compromised by water-deficit, which
      could favor the growth of aphid populations. Overall, the first trophic level
      under water-deficit stress was shown to have an indirect and negative impact on
      the third trophic level parasitoid, suggesting that parasitoids could be
      increasingly vulnerable in future warming scenarios.

PMID- 29053723
TI  - Heart rate variability and baroreceptor reflex sensitivity in early- versus late
      onset preeclampsia.
AB  - OBJECTIVE: To determine whether there are differences in autonomic nervous system
      function in early- versus late-onset preeclampsia. METHODS: Matched case-control
      study. Cases were defined as singleton pregnancies with preeclampsia at < 34+0
      weeks of gestation (early-onset preeclampsia) and >= 34+0 weeks of gestation
      (late-onset preeclampsia). For each case in each of the preeclampsia subgroups,
      three "control"uncomplicated singleton pregnancies were matched by maternal age,
      height, and week of gestation. Blood pressure and heart rate were measured
      continuously for 30 minutes in each participant. Baroreceptor reflex sensitivity
      (assessed using sequence technique), time and frequency domain heart rate
      variability measures, as SDNN, RMSSD, LFRRI, HFRRI and LF/HFRRI of R-R intervals,
      were compared between groups (p<0.05 significant). RESULTS: 24 women with
      preeclampsia (10 with early-onset and 14 with late-onset preeclampsia) and 72
      controls were included in the study. SDNN, RMSSD and HFRRI were significantly
      higher in the late-onset preeclampsia group compared to gestational age matched
      controls (p = 0.033, p = 0.002 and p = 0.018, respectively). No significant
      differences in SDNN RMSSD and HFRRI between early-onset preeclampsia group and
      gestational age matched controls were observed (p = 0.304, p = 0.325 and p =
      0.824, respectively). Similarly, baroreceptor reflex sensitivity was higher in
      late-onset preeclampsia compared to controls at >= 34 weeks (p = 0.037), but not
      different between early-onset preeclampsia compared to controls at < 34 weeks (p
      = 0.50). CONCLUSIONS: Heart rate variability and baroreceptor reflex sensitivity
      are increased in late- but not early-onset preeclampsia compared to healthy
      pregnancies. This indicates a better autonomic nervous system mediated adaptation
      to preeclampsia related cardiovascular changes in late-onset disease.

PMID- 29053721
TI  - XX Disorder of Sex Development is associated with an insertion on chromosome 9
      and downregulation of RSPO1 in dogs (Canis lupus familiaris).
AB  - Remarkable progress has been achieved in understanding the mechanisms controlling
      sex determination, yet the cause for many Disorders of Sex Development (DSD)
      remains unknown. Of particular interest is a rare XX DSD subtype in which
      individuals are negative for SRY, the testis determining factor on the Y
      chromosome, yet develop testes or ovotestes, and both of these phenotypes occur
      in the same family. This is a naturally occurring disorder in humans (Homo
      sapiens) and dogs (C. familiaris). Phenotypes in the canine XX DSD model are
      strikingly similar to those of the human XX DSD subtype. The purposes of this
      study were to identify 1) a variant associated with XX DSD in the canine model
      and 2) gene expression alterations in canine embryonic gonads that could be
      informative to causation. Using a genome wide association study (GWAS) and whole
      genome sequencing (WGS), we identified a variant on C. familiaris autosome 9
      (CFA9) that is associated with XX DSD in the canine model and in affected
      purebred dogs. This is the first marker identified for inherited canine XX DSD.
      It lies upstream of SOX9 within the canine ortholog for the human disorder, which
      resides on 17q24. Inheritance of this variant indicates that XX DSD is a complex
      trait in which breed genetic background affects penetrance. Furthermore, the
      homozygous variant genotype is associated with embryonic lethality in at least
      one breed. Our analysis of gene expression studies (RNA-seq and PRO-seq) in
      embryonic gonads at risk of XX DSD from the canine model identified significant
      RSPO1 downregulation in comparison to XX controls, without significant
      upregulation of SOX9 or other known testis pathway genes. Based on these data, a
      novel mechanism is proposed in which molecular lesions acting upstream of RSPO1
      induce epigenomic gonadal mosaicism.

PMID- 29053724
TI  - Accounting for the complex hierarchical topology of EEG phase-based functional
      connectivity in network binarisation.
AB  - Research into binary network analysis of brain function faces a methodological
      challenge in selecting an appropriate threshold to binarise edge weights. For EEG
      phase-based functional connectivity, we test the hypothesis that such
      binarisation should take into account the complex hierarchical structure found in
      functional connectivity. We explore the density range suitable for such structure
      and provide a comparison of state-of-the-art binarisation techniques, the
      recently proposed Cluster-Span Threshold (CST), minimum spanning trees,
      efficiency-cost optimisation and union of shortest path graphs, with arbitrary
      proportional thresholds and weighted networks. We test these techniques on
      weighted complex hierarchy models by contrasting model realisations with small
      parametric differences. We also test the robustness of these techniques to random
      and targeted topological attacks. We find that the CST performs consistenty well
      in state-of-the-art modelling of EEG network topology, robustness to topological
      network attacks, and in three real datasets, agreeing with our hypothesis of
      hierarchical complexity. This provides interesting new evidence into the
      relevance of considering a large number of edges in EEG functional connectivity
      research to provide informational density in the topology.

PMID- 29053725
TI  - The effects of training with loads that maximise power output and individualised
      repetitions vs. traditional power training.
AB  - BACKGROUND: It has been suggested that strength training effects (i.e. neural or
      structural) vary, depending on the total repetitions performed and velocity loss
      in each training set. PURPOSE: The aim of this study is to compare the effects of
      two training programmes (i.e. one with loads that maximise power output and
      individualised repetitions, and the other following traditional power training).
      METHODS: Twenty-five males were divided into three groups (optimum power [OP =
      10], traditional training [TT = 9] and control group [CG = 6]). The training load
      used for OP was individualised using loads that maximised power output (41.7% +/-
      5.8 of one repetition maximum [1RM]) and repetitions at maximum power (4 to 9
      repetitions, or 'reps'). Volume (sets x repetitions) was the same for both
      experimental groups, while intensity for TT was that needed to perform only 50%
      of the maximum number of possible repetitions (i.e. 61.1%-66.6% of 1RM). The
      training programme ran over 11 weeks (2 sessions per week; 4-5 sets per session;
      3-minute rests between sets), with pre-, intermediate and post-tests which
      included: anthropometry, 1RM, peak power output (PPO) with 30%, 40% and 50% of
      1RM in the bench press throw, and salivary testosterone (ST) and cortisol (SC)
      concentrations. Rate of perceived exertion (RPE) and power output were recorded
      in all sessions. RESULTS: Following the intermediate test, PPO was increased in
      the OP group for each load (10.9%-13.2%). Following the post-test, both
      experimental groups had increased 1RM (11.8%-13.8%) and PPO for each load (14.1%
      19.6%). Significant decreases in PPO were found for the TT group during all sets
      (4.9%-15.4%), along with significantly higher RPE (37%). CONCLUSION: OP appears
      to be a more efficient method of training, with less neuromuscular fatigue and
      lower RPE.

PMID- 29053726
TI  - Prevalence of deleterious germline variants in risk genes including BRCA1/2 in
      consecutive ovarian cancer patients (AGO-TR-1).
AB  - BACKGROUND: Identification of families at risk for ovarian cancer offers the
      opportunity to consider prophylactic surgery thus reducing ovarian cancer
      mortality. So far, identification of potentially affected families in Germany was
      solely performed via family history and numbers of affected family members with
      breast or ovarian cancer. However, neither the prevalence of deleterious variants
      in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as
      trigger for genetic counselling has ever been evaluated. METHODS: Prospective
      counseling and germline testing of consecutive patients with primary diagnosis or
      with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing
      included 25 candidate and established risk genes. Among these 25 genes, 16 genes
      (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2,
      RAD51C, RAD51D, STK11, TP53) were defined as established cancer risk genes. A
      positive family history was defined as at least one relative with breast cancer
      or ovarian cancer or breast cancer in personal history. RESULTS: In total, we
      analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and
      242 patients with relapsed disease. Median age at primary diagnosis was 58 years
      (range 16-93) and 406 patients (77.6%) had a high-grade serous ovarian cancer. In
      total, 27.9% of the patients showed at least one deleterious variant in all 25
      investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants
      were most prevalent in the BRCA1 (15.5%), BRCA2 (5.5%), RAD51C (2.5%) and PALB2
      (1.1%) genes. The prevalence of deleterious variants did not differ significantly
      between patients at primary diagnosis and relapse. The prevalence of deleterious
      variants in BRCA1/2 (and in all 16 risk genes) in patients <60 years was 30.2%
      (33.2%) versus 10.6% (18.9%) in patients >=60 years. Family history was positive
      in 43% of all patients. Patients with a positive family history had a prevalence
      of deleterious variants of 31.6% (36.0%) versus 11.4% (17.6%) and histologic
      subtype of high grade serous ovarian cancer versus other showed a prevalence of
      deleterious variants of 23.2% (29.1%) and 10.2% (14.8%), respectively. Testing
      only for BRCA1/2 would miss in our series more than 5% of the patients with a
      deleterious variant in established risk genes. CONCLUSIONS: 26.4% of all patients
      harbor at least one deleterious variant in established risk genes. The threshold
      of 10% mutation rate which is accepted for reimbursement by health care providers
      in Germany was observed in all subgroups analyzed and neither age at primary
      diagnosis nor histo-type or family history sufficiently enough could identify a
      subgroup not eligible for genetic counselling and testing. Genetic testing should
      therefore be offered to every patient with invasive epithelial ovarian cancer and
      limiting testing to BRCA1/2 seems to be not sufficient.

PMID- 29053727
TI  - Impaired glucose metabolism in subjects with the Williams-Beuren syndrome: A five
      year follow-up cohort study.
AB  - OBJECTIVE: The Williams-Beuren syndrome (WS) is associated with impaired glucose
      metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains
      poorly defined, due to the lack of longitudinal studies investigating the
      contribution of beta-cell dysfunction and impaired insulin sensitivity. This
      study aimed at assessing incidence of IGM and the underlying mechanisms in WS
      adults. METHODS: This observational, longitudinal (5-year), cohort study enrolled
      thirty-one consecutive WS subjects attending a tertiary referral center. An oral
      glucose tolerance test (OGTT) was performed yearly and used to classify patients
      as normal or IGM, including impaired fasting glucose (IFG) and/or impaired
      glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate
      measures of insulin secretion and/or sensitivity. RESULTS: IGM patients were 18
      (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up.
      However, 13 individuals changed category of glucose homeostasis in both
      directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non
      progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per
      100 persons-year, respectively, and were treated non-pharmacologically. In the
      whole cohort and, to a higher extent, in progressors, indices of early-phase
      insulin secretion and insulin sensitivity decreased significantly from baseline
      to end-of-follow-up, with concurrent reduction of the oral disposition index and
      insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion
      for the level of insulin resistance. No baseline measure independently predicted
      progression, which correlated with change from baseline in ISSI-2. Compared with
      patients with normal glucose homeostasis, IGT subjects had impaired insulin
      sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or
      DM. CONCLUSIONS: IGM incidence is high in young adults with WS, suggesting the
      need of early screening and timed intervention. As in classical type 2 diabetes,
      impaired insulin sensitivity and beta-cell dysfunction contribute, in this
      sequence, to progression to IGM and DM.

PMID- 29053728
TI  - Density, abundance, survival, and ranging patterns of common bottlenose dolphins
      (Tursiops truncatus) in Mississippi Sound following the Deepwater Horizon oil
      spill.
AB  - After the Deepwater Horizon (DWH) oil spill began in April 2010, studies were
      initiated on northern Gulf of Mexico common bottlenose dolphins (Tursiops
      truncatus) in Mississippi Sound (MSS) to determine density, abundance, and
      survival, during and after the oil spill, and to compare these results to
      previous research in this region. Seasonal boat-based photo-identification
      surveys (2010-2012) were conducted in a section of MSS to estimate dolphin
      density and survival, and satellite-linked telemetry (2013) was used to determine
      ranging patterns. Telemetry suggested two different ranging patterns in MSS: (1)
      inshore waters with seasonal movements into mid-MSS, and (2) around the barrier
      islands exclusively. Based upon these data, dolphin density was estimated in two
      strata (Inshore and Island) using a spatially-explicit robust-design capture
      recapture model. Inshore and Island density varied between 0.77-1.61 dolphins km
      2 ([Formula: see text] = 1.42, 95% CI: 1.28-1.53) and 3.32-5.74 dolphins km-2
      ([Formula: see text] = 4.43, 95% CI: 2.70-5.63), respectively. The estimated
      annual survival rate for dolphins with distinctive fins was very low in the year
      following the spill, 0.73 (95% CI: 0.67-0.78), and consistent with the occurrence
      of a large scale cetacean unusual mortality event that was in part attributed to
      the DWH oil spill. Fluctuations in density were not as large or seasonally
      consistent as previously reported. Total abundance for MSS extrapolated from
      density results ranged from 4,610 in July 2011 to 3,046 in January 2012
      ([Formula: see text] = 3,469, 95% CI: 3,113-3,725).

PMID- 29053729
TI  - The influence of the selection of macronutrients coupled with dietary energy
      density on the performance of broiler chickens.
AB  - A total of 360 male Ross 308 broiler chickens were used in a feeding study to
      assess the influence of macronutrients and energy density on feed intakes from 10
      to 31 days post-hatch. The study comprised ten dietary treatments from five
      dietary combinations and two feeding approaches: sequential and choice feeding.
      The study included eight experimental diets and each dietary combination was made
      from three experimental diets. Choice fed birds selected between three diets in
      separate feed trays at the same time; whereas the three diets were offered to
      sequentially fed birds on an alternate basis during the experimental period.
      There were no differences between starch and protein intakes between choice and
      sequentially fed birds (P > 0.05) when broiler chickens selected between diets
      with different starch, protein and lipid concentrations. When broiler chickens
      selected between diets with different starch and protein but similar lipid
      concentrations, both sequentially and choice fed birds selected similar ratios of
      starch and protein intake (P > 0.05). However, when broiler chickens selected
      from diets with different protein and lipid but similar starch concentrations,
      choice fed birds had higher lipid intake (129 versus 118 g/bird, P = 0.027) and
      selected diets with lower protein concentrations (258 versus 281 g/kg, P = 0.042)
      than birds offered sequential diet options. Choice fed birds had greater intakes
      of the high energy diet (1471 g/bird, P < 0.0001) than low energy (197 g/bird) or
      medium energy diets (663 g/bird) whilst broiler chickens were offered diets with
      different energy densities but high crude protein (300 g/kg) or digestible lysine
      (17.5 g/kg) concentrations. Choice fed birds had lower FCR (1.217 versus 1.327
      g/g, P < 0.0001) and higher carcass yield (88.1 versus 87.3%, P = 0.012) than
      sequentially fed birds. This suggests that the dietary balance between protein
      and energy is essential for optimal feed conversion efficiency. The intake path
      of macronutrients from 10-31 days in choice and sequential feeding groups were
      plotted and compared with the null path if broiler chickens selected equal
      amounts of the three diets in the combination. Regardless of feeding regimen, the
      intake paths of starch and protein are very close to the null path; however,
      lipid and protein intake paths in choice fed birds are father from the null path
      than sequentially fed birds.

PMID- 29053730
TI  - Assessment of intra and interregional genetic variation in the Eastern Red-backed
      Salamander, Plethodon cinereus, via analysis of novel microsatellite markers.
AB  - The red-backed salamander (Plethodon cinereus) has long-served as a model system
      in ecology, evolution, and behavior, and studies surveying molecular variation in
      this species have become increasingly common over the past decade. However,
      difficulties are commonly encountered when extending microsatellite markers to
      populations that are unstudied from a genetic perspective due to high levels of
      genetic differentiation across this species' range. To ameliorate this issue, we
      used 454 pyrosequencing to identify hundreds of microsatellite loci. We then
      screened 40 of our top candidate loci in populations in Virginia, Pennsylvania,
      and Ohio-including an isolated island population ~ 4.5 km off the shore of Lake
      Erie (South Bass Island). We identified 25 loci that are polymorphic in a well
      studied region of Virginia and 11 of these loci were polymorphic in populations
      located in the genetically unstudied regions of Ohio and Pennsylvania. Use of
      these loci to examine patterns of variation within populations revealed that
      South Bass Island has low diversity in comparison to other sites. However,
      neither South Bass Island nor isolated populations around Cleveland are inbred.
      Assessment of variation between populations revealed three well defined genetic
      clusters corresponding to Virginia, mainland Ohio/Pennsylvania, and South Bass
      Island. Comparisons of our results to those of others working in various parts of
      the range are consistent with the idea that differentiation is lower in regions
      that were once glaciated. However, these comparisons also suggest that well
      differentiated isolated populations in the formerly glaciated portion of the
      range are not uncommon. This work provides novel genetic resources that will
      facilitate population genetic studies in a part of the red-backed salamander's
      range that has not previously been studied in this manner. Moreover, this work
      refines our understanding of how neutral variation is distributed in this
      ecologically important organism.

PMID- 29053731
TI  - Determination of MU-, delta- and kappa-opioid receptors in forebrain cortex of
      rats exposed to morphine for 10 days: Comparison with animals after 20 days of
      morphine withdrawal.
AB  - BACKGROUND: Chronic exposure of mammalian organism to morphine results in
      adaption to persistent high opioid tone through homeostatic adjustments. Our
      previous results indicated that in the frontal brain cortex (FBC) of rats exposed
      to morphine for 10 days, such a compensatory adjustment was detected as large up
      regulation of adenylylcyclases I (8-fold) and II (2.5-fold). The other isoforms
      of AC (III-IX) were unchanged. Importantly, the increase of ACI and ACII was
      reversible as it disappeared after 20 days of morphine withdrawal. Changes of
      down-stream signaling molecules such as G proteins and adenylylcyclases should
      respond to and be preceded by primary changes proceeding at receptor level.
      Therefore in our present work, we addressed the problem of reversibility of the
      long-term morphine effects on MU-, delta- and kappa-OR protein levels in FBC.
      METHODS: Rats were exposed to increasing doses of morphine (10-40 mg/kg) for 10
      days and sacrificed either 24 h (group +M10) or 20 days (group +M10/-M20) after
      the last dose of morphine in parallel with control animals (groups -M10 and -M10/
      M20). Post-nuclear supernatant (PNS) fraction was prepared from forebrain cortex,
      resolved by 1D-SDS-PAGE under non-dissociated (-DTT) and dissociated (+DTT)
      conditions, and analyzed for the content of MU-, delta- and kappa-OR by
      immunoblotting with C- and N-terminus oriented antibodies. RESULTS: Significant
      down-regulation of delta-OR form exhibiting Mw ~ 60 kDa was detected in PNS
      prepared from both (+M10) and (+M10/-M20) rats. However, the total immunoblot
      signals of MU-, delta- and kappa-OR, respectively, were unchanged. Plasma
      membrane marker Na, K-ATPase, actin and GAPDH were unaffected by morphine in both
      types of PNS. Membrane-domain marker caveolin-1 and cholesterol level increased
      in (+M10) rats and this increase was reversed back to control level in (+M10/
      M20) rats. CONCLUSIONS: In FBC, prolonged exposure of rats to morphine results in
      minor (delta-OR) or no change (MU- and kappa-OR) of opioid receptor content. The
      reversible increases of caveolin-1 and cholesterol levels suggest participation
      of membrane domains in compensatory responses during opioid withdrawal. GENERAL
      SIGNIFICANCE: Analysis of reversibility of morphine effect on mammalian brain.

PMID- 29053732
TI  - Body typing of children and adolescents using 3D-body scanning.
AB  - Three-dimensional (3D-) body scanning of children and adolescents allows the
      detailed study of physiological development in terms of anthropometrical
      alterations which potentially provide early onset markers for obesity. Here, we
      present a systematic analysis of body scanning data of 2,700 urban children and
      adolescents in the age range between 5 and 18 years with the special aim to
      stratify the participants into distinct body shape types and to describe their
      change upon development. In a first step, we extracted a set of eight
      representative meta-measures from the data. Each of them collects a related group
      of anthropometrical features and changes specifically upon aging. In a second
      step we defined seven body types by clustering the meta-measures of all
      participants. These body types describe the body shapes in terms of three weight
      (lower, normal and overweight) and three age (young, medium and older)
      categories. For younger children (age of 5-10 years) we found a common 'early
      childhood body shape' which splits into three weight-dependent types for older
      children, with one or two years delay for boys. Our study shows that the concept
      of body types provides a reliable option for the anthropometric characterization
      of developing and aging populations.

PMID- 29053733
TI  - Novel calpain families and novel mechanisms for calpain regulation in Aplysia.
AB  - Calpains are a family of intracellular proteases defined by a conserved protease
      domain. In the marine mollusk Aplysia californica, calpains are important for the
      induction of long-term synaptic plasticity and memory, at least in part by
      cleaving protein kinase Cs (PKCs) into constitutively active kinases, termed
      protein kinase Ms (PKMs). We identify 14 genes encoding calpains in Aplysia using
      bioinformatics, including at least one member of each of the four major calpain
      families into which metazoan calpains are generally classified, as well as
      additional truncated and atypical calpains. Six classical calpains containing a
      penta-EF-hand (PEF) domain are present in Aplysia. Phylogenetic analysis
      determined that these six calpains come from three separate classical calpain
      families. One of the classical calpains in Aplysia, AplCCal1, has been implicated
      in plasticity. We identify three splice cassettes and an alternative
      transcriptional start site in AplCCal1. We characterize several of the possible
      isoforms of AplCCal1 in vitro, and demonstrate that AplCCal1 can cleave PKCs into
      PKMs in a calcium-dependent manner in vitro. We also find that AplCCal1 has a
      novel mechanism of auto-inactivation through N-terminal cleavage that is
      modulated through its alternative transcriptional start site.

PMID- 29053734
TI  - An instrument to assess the statistical intensity of medical research papers.
AB  - BACKGROUND: There is widespread evidence that statistical methods play an
      important role in original research articles, especially in medical research. The
      evaluation of statistical methods and reporting in journals suffers from a lack
      of standardized methods for assessing the use of statistics. The objective of
      this study was to develop and evaluate an instrument to assess the statistical
      intensity in research articles in a standardized way. METHODS: A checklist-type
      measure scale was developed by selecting and refining items from previous reports
      about the statistical contents of medical journal articles and from published
      guidelines for statistical reporting. A total of 840 original medical research
      articles that were published between 2007-2015 in 16 journals were evaluated to
      test the scoring instrument. The total sum of all items was used to assess the
      intensity between sub-fields and journals. Inter-rater agreement was examined
      using a random sample of 40 articles. Four raters read and evaluated the selected
      articles using the developed instrument. RESULTS: The scale consisted of 66
      items. The total summary score adequately discriminated between research articles
      according to their study design characteristics. The new instrument could also
      discriminate between journals according to their statistical intensity. The inter
      observer agreement measured by the ICC was 0.88 between all four raters.
      Individual item analysis showed very high agreement between the rater pairs, the
      percentage agreement ranged from 91.7% to 95.2%. CONCLUSIONS: A reliable and
      applicable instrument for evaluating the statistical intensity in research papers
      was developed. It is a helpful tool for comparing the statistical intensity
      between sub-fields and journals. The novel instrument may be applied in
      manuscript peer review to identify papers in need of additional statistical
      review.

PMID- 29053735
TI  - Characterization of the first knock-out aldh7a1 zebrafish model for pyridoxine
      dependent epilepsy using CRISPR-Cas9 technology.
AB  - Pyridoxine dependent epilepsy (PDE) is caused by likely pathogenic variants in
      ALDH7A1 (PDE-ALDH7A1) and inherited autosomal recessively. Neurotoxic alpha-amino
      adipic semialdehyde (alpha-AASA), piperideine 6-carboxylate and pipecolic acid
      accumulate in body fluids. Neonatal or infantile onset seizures refractory to
      anti-epileptic medications are clinical features. Treatment with pyridoxine,
      arginine and lysine-restricted diet does not normalize neurodevelopmental outcome
      or accumulation of neurotoxic metabolites. There is no animal model for high
      throughput drug screening. For this reason, we developed and characterized the
      first knock-out aldh7a1 zebrafish model using CRISPR-Cas9 technology. Zebrafish
      aldh7a1 mutants were generated by using a vector free method of CRISPR-Cas9
      mutagenesis. Genotype analysis of aldh7a1 knock-out zebrafish was performed by
      high resolution melt analysis, direct sequencing and QIAxcel system.
      Electroencephalogram was performed. Alpha-AASA, piperideine 6-carboxylate and
      pipecolic acid, were measured by liquid chromatography-tandem mass spectrometry.
      Our knock-out aldh7a1 zebrafish has homozygous 5 base pair (bp) mutation in
      ALDH7A1. Knock-out aldh7a1 embryos have spontaneous rapid increase in locomotion
      and a rapid circling swim behavior earliest 8-day post fertilization (dpf).
      Electroencephalogram revealed large amplitude spike discharges compared to wild
      type. Knock-out aldh7a1 embryos have elevated alpha-AASA, piperideine 6
      carboxylate and pipecolic acid compared to wild type embryos at 3 dpf. Knock-out
      aldh7a1 embryos showed no aldh7a1 protein by western blot compared to wild type.
      Our knock-out aldh7a1 zebrafish is a well characterized model for large-scale
      drug screening using behavioral and biochemical features and accurately
      recapitulates the human PDE-ALDH7A1 disease.

PMID- 29053736
TI  - Assessment of fitness for duty of underperforming physicians: The importance of
      using appropriate norms.
AB  - OBJECTIVE: To determine whether population-specific normative data should be
      employed when screening neurocognitive functioning as part of physician fitness
      for duty evaluations. If so, to provide such norms based on the evidence
      currently available. METHODS: A comparison of published data from four sources
      was analyzed. Data from the two physician samples were then entered into a meta
      analysis to obtain full information estimates and generate provisional norms for
      physicians. RESULTS: Two-way analysis of variance (Study x Index) revealed a
      significant main effect and an interaction. Results indicate differences in mean
      levels of performance and standard deviation for physicians. CONCLUSIONS:
      Reliance on general population normative data results in under-identification of
      potential neuropsychological difficulties. Population specific normative data are
      needed to effectively evaluate practicing physicians.

PMID- 29053737
TI  - Screening for HIV, hepatitis B and syphilis on dried blood spots: A promising
      method to better reach hidden high-risk populations with self-collected sampling.
AB  - INTRODUCTION: Many people at high risk for sexually transmitted infections
      (STIs), e.g., men who have sex with men (MSM), are not optimally reached by
      current sexual health care systems with testing. To facilitate testing by home
      based sampling or sampling in outreach setting we evaluated dried blood spots
      (DBS), a method for self-collected blood sampling for serological screening of
      HIV, hepatitis B (HBV) and syphilis. The aims of this study were to assess the
      acceptability and feasibility of self-collected DBS and to compare the test
      results for screening of HIV, HBV and syphilis from DBS with blood drawn by
      venous puncture. METHODS: DBS were collected from men who have sex with men
      (MSM), visiting the STI clinic of the public health service South Limburg (n =
      183) and HIV positive and HBV positive patients (n = 34), visiting the outpatient
      clinics of the Maastricht University Medical Centre in the period January 2012
      April 2015. The 93 first participating MSM visiting the STI clinic were asked to
      fill in a questionnaire about the feasibility and acceptability about self
      collection of DBS in a setting without going to a health care facility and were
      asked to collect the DBS themselves. Serological screening tests for HIV (HIV
      combi PT, Roche), HBV (HBsAg, Roche) and syphilis (Treponema pallidum Ig, Biokit
      3.0) were performed on DBS and on blood drawn by venous puncture, which was
      routinely taken for screening. RESULTS: In total 217 participants were included
      in the study with a median age of 40 years (range between 17-80). Of MSM 84%
      agreed that it was clear and easy to do the finger-prick, while 53% agreed that
      it was clear and easy to apply the blood onto the DBS card. Also, 80% of MSM
      would use the bloodspot test again. In 91% (198) of DBS, sufficient material was
      collected to perform the three tests. No difference was observed in DBS quality
      between self-collected DBS and health care worker collected DBS. For HIV (n = 195
      DBS-serum pairs) sensitivity and specificity were 100%. For HBV the sensitivity
      for HBsAg (n = 202) was 90% and specificity was 99%. For syphilis (n = 191) the
      sensitivity of the DBS was 93% with a specificity of 99%. Analysis of the DBS of
      HIV positive participants (n = 38) did show similar test performance for HBV and
      syphilis as in HIV negatives. CONCLUSION: DBS is an acceptable self-sampling
      method for MSM, as there was no difference in DBS quality in self-collected and
      health care worker collected DBS. Test performance, i.e., its high sensitivity
      (>90%) and specificity (>99%) measures show that DBS is a valid alternative for
      venous blood puncture. Especially when DBS is combined with home-collected
      sampling for Chlamydia trachomatis and Neisseria gonorrhoeae, complete STI
      screening can be done in outreach setting and/or home-collected sampling in MSM.

PMID- 29053738
TI  - Neotropical peatland methane emissions along a vegetation and biogeochemical
      gradient.
AB  - Tropical wetlands are thought to be the most important source of interannual
      variability in atmospheric methane (CH4) concentrations, yet sparse data prevents
      them from being incorporated into Earth system models. This problem is
      particularly pronounced in the neotropics where bottom-up models based on water
      table depth are incongruent with top-down inversion models suggesting unaccounted
      sinks or sources of CH4. The newly documented vast areas of peatlands in the
      Amazon basin may account for an important unrecognized CH4 source, but the
      hydrologic and biogeochemical controls of CH4 dynamics from these systems remain
      poorly understood. We studied three zones of a peatland in Madre de Dios, Peru,
      to test whether CH4 emissions and pore water concentrations varied with
      vegetation community, soil chemistry and proximity to groundwater sources. We
      found that the open-canopy herbaceous zone emitted roughly one-third as much CH4
      as the Mauritia flexuosa palm-dominated areas (4.7 +/- 0.9 and 14.0 +/- 2.4 mg
      CH4 m-2 h-1, respectively). Emissions decreased with distance from groundwater
      discharge across the three sampling sites, and tracked changes in soil carbon
      chemistry, especially increased soil phenolics. Based on all available data, we
      calculate that neotropical peatlands contribute emissions of 43 +/- 11.9 Tg CH4 y
      1, however this estimate is subject to geographic bias and will need revision
      once additional studies are published.

PMID- 29053739
TI  - Simultaneous introgression of three POLLED mutations into a synthetic breed of
      Chinese cattle.
AB  - The polled phenotype of cattle is increasingly becoming favourable mainly because
      of the enhanced emphasis on animal welfare, for which the causative mutations
      have been reported during the past years. The Shuxuan cattle are a new synthetic
      breed by crossing the indigenous cattle with both Simmental and Holstein semen in
      Sichuan of Southwest China, in which about 15% of polled individuals have newly
      emerged. Because official record about POLLED genotypes for the historically
      imported sires is unavailable, we therefore genotyped the proposed POLLED
      variants of P202ID, P80kbID and P219ID among 48 polled and 16 horned Shuxuan
      cattle. It was first revealed that all three candidate mutations have been
      simultaneously introgressed into Shuxuan cattle, whereas the P202ID mutation is
      dominant. Furthermore, one polled animal still remains to carry none of the three
      candidate mutations, which suggests that further mutation(s) would also exist.
      Additionally, we sequenced mitochondrial DNA and found that Shuxuan cattle are
      composed of two matrilineal origins of Bos taurus (65.6%) and B. indicus (34.4%);
      and there is no origin-biased distribution of polled phenotype. In conclusion,
      our study first supports the recently reported novel candidate mutation of P219ID
      and detects simultaneous presences of all three known POLLED mutations within a
      cattle breed.

PMID- 29053740
TI  - Gene flow of common ash (Fraxinus excelsior L.) in a fragmented landscape.
AB  - Gene flow dynamics of common ash (Fraxinus excelsior L.) is affected by several
      human activities in Central Europe, including habitat fragmentation, agroforestry
      expansion, controlled and uncontrolled transfer of reproductive material, and a
      recently introduced emerging infectious disease, ash dieback, caused by
      Hymenoscyphus fraxineus. Habitat fragmentation may alter genetic connectivity and
      effective population size, leading to loss of genetic diversity and increased
      inbreeding in ash populations. Gene flow from cultivated trees in landscapes
      close to their native counterparts may also influence the adaptability of future
      generations. The devastating effects of ash dieback have already been observed in
      both natural and managed populations in continental Europe. However, potential
      long-term effects of genetic bottlenecks depend on gene flow across fragmented
      landscapes. For this reason, we studied the genetic connectivity of ash trees in
      an isolated forest patch of a fragmented landscape in Rosenbeck, Germany. We
      applied two approaches to parentage analysis to estimate gene flow patterns at
      the study site. We specifically investigated the presence of background
      pollination at the landscape level and the degree of genetic isolation between
      native and cultivated trees. Local meteorological data was utilized to understand
      the effect of wind on the pollen and seed dispersal patterns. Gender information
      of the adult trees was considered for calculating the dispersal distances. We
      found that the majority of the studied seeds (55-64%) and seedlings (75-98%) in
      the forest patch were fathered and mothered by the trees within the same patch.
      However, we determined a considerable amount of pollen flow (26-45%) from outside
      of the study site, representing background pollination at the landscape level.
      Limited pollen flow was observed from neighbouring cultivated trees (2%). Both
      pollen and seeds were dispersed in all directions in accordance with the local
      wind directions. Whereas there was no positive correlation between pollen
      dispersal distance and wind speed, the correlation between seed dispersal
      distance and wind speed was significant (0.71, p < 0.001), indicating that strong
      wind favours long-distance dispersal of ash seeds. Finally, we discussed the
      implications of establishing gene conservation stands and the use of enrichment
      planting in the face of ash dieback.

PMID- 29053741
TI  - The importance of propolis in alleviating the negative physiological effects of
      heat stress in quail chicks.
AB  - Heat stress is one of the most detrimental confrontations in tropical and
      subtropical regions of the world, causing considerable economic losses in poultry
      production. Propolis, a resinous product of worker honeybees, possesses several
      biological activities that could be used to alleviate the deleterious effects of
      high environmental temperature on poultry production. The current study was aimed
      at evaluating the effects of propolis supplementation to Japanese quail (Coturnix
      coturnix japonica) diets on the production performance, intestinal
      histomorphology, relative physiological and immunological parameters, and
      selected gene expression under heat stress conditions. Three hundred one-day-old
      Japanese quail chicks were randomly distributed into 20 wired-cages. At 28 d of
      age, the birds were divided into 2 temperature treatment groups; a normal at 24
      degrees C (C group) and a heat stress at 35 degrees C (HS group). The birds in
      each group were further assigned to 2 subgroups; one of them was fed on a basal
      diet without propolis supplementation (-Pr subgroup) while the other was
      supplemented with propolis (+Pr subgroup). Production performance including body
      weight gain, feed intake and feed conversion ratio were measured. The intestinal
      histomorphological measurements were also performed for all treatment groups.
      Relative physiological parameters including body temperature, corticosterone
      hormone level, malondialdehyde (MDA) and free triiodothyronine hormone (fT3), as
      well as the relative immunological parameters including the total white blood
      cells count (TWBC's), heterophil/lymphocyte (H/L) ratio and lymphocyte
      proliferation index, were also measured. Furthermore, the mRNA expression for
      toll like receptor 5 (TLR5), cysteine-aspartic protease-6 (CASP6) and heat shock
      proteins 70 and 90 (Hsp70 and Hsp90) genes was quantified in this study. The
      quail production performance was significantly (P<0.05) impaired by HS treatment,
      while Pr treatment significantly improved the quail production performance. The
      villus width and area were significantly (P<0.05) lower in the HS compared to the
      C group, while Pr treatment significantly increased crypts depth of quail. A
      negative impact of HS treatment was observed on the physiological status of
      quail; however, propolis significantly alleviated this negative effect. Moreover,
      quail of the HS group expressed lower immunological parameters than C group,
      while propolis enhanced the immune status of the quail. The relative mRNA
      expression of TLR5 gene was down-regulated by HS treatment while it was up
      regulated by the Pr treatment. Furthermore, the positive effects of propolis in
      HS-quail were evidenced by normalizing the high expressions of CASP6 and Hsp70
      genes when compared to the C group. Based on these results, the addition of
      propolis to quail diets as a potential nutritional strategy in order to improve
      their performance, especially under heat stress conditions, is recommended.

PMID- 29053742
TI  - Are current chronic fatigue syndrome criteria diagnosing different disease
      phenotypes?
AB  - IMPORTANCE: Chronic fatigue syndrome (CFS) is characterised by a constellation of
      symptoms diagnosed with a number of different polythetic criteria. Heterogeneity
      across these diagnostic criteria is likely to be confounding research into the as
      yet-unknown pathophysiology underlying this stigmatised and debilitating
      condition and may diagnose a disease spectrum with significant implications for
      clinical management. No studies to date have objectively investigated this
      possibility using a validated measure of CFS symptoms-the DePaul Symptom
      Questionnaire (DSQ). OBJECTIVE: To examine whether current CFS diagnostic
      criteria are identifying different disease phenotypes using the DSQ. DESIGN: Case
      control study. SETTING: Clinical Research Facility of the Royal Victoria
      Infirmary, Newcastle upon Tyne, UK. PARTICIPANTS: 49 CFS subjects and ten
      matched, sedentary community controls, excluded for co-morbid depression. MAIN
      OUTCOMES AND MEASURES: Self-reported autonomic and cognitive features were
      assessed with the Composite Autonomic Symptom Score (COMPASS) and Cognitive
      Failures Questionnaire (COGFAIL) respectively. Objective autonomic cardiovascular
      parameters were examined using the Task Force(r) Monitor and a battery of
      neuropsychological tests administered for objective cognitive assessment.
      RESULTS: Self-reported autonomic and cognitive symptoms were significantly
      greater in CFS subjects compared to controls. There were no statistically
      significant differences in objective autonomic measures between CFS and controls.
      There were clinically significant differences between DSQ subgroups on objective
      autonomic testing. Visuospatial memory, verbal memory and psychomotor speed were
      significantly different between DSQ subgroups. CONCLUSIONS AND RELEVANCE: The
      finding of no significant differences in objective autonomic testing between CFS
      and control subjects may reflect the inclusion of sedentary controls or exclusion
      for co-morbid depression. Consistent exclusion criteria would enable better
      delineation of these two conditions and their presenting symptoms. Findings
      across CFS subgroups suggest subjects have a different disease burden on
      subjective and objective measures of function, autonomic parameters and cognitive
      impairment when categorised using the DSQ. Different CFS criteria may at best be
      diagnosing a spectrum of disease severities and at worst different CFS phenotypes
      or even different diseases. This complicates research and disease management and
      may contribute to the significant stigma associated with the condition.

PMID- 29053744
TI  - Transition to reconstructibility in weakly coupled networks.
AB  - Across scientific disciplines, thresholded pairwise measures of statistical
      dependence between time series are taken as proxies for the interactions between
      the dynamical units of a network. Yet such correlation measures often fail to
      reflect the underlying physical interactions accurately. Here we systematically
      study the problem of reconstructing direct physical interaction networks from
      thresholding correlations. We explicate how local common cause and relay
      structures, heterogeneous in-degrees and non-local structural properties of the
      network generally hinder reconstructibility. However, in the limit of weak
      coupling strengths we prove that stationary systems with dynamics close to a
      given operating point transition to universal reconstructiblity across all
      network topologies.

PMID- 29053743
TI  - In vitro modeling of experimental succinic semialdehyde dehydrogenase deficiency
      (SSADHD) using brain-derived neural stem cells.
AB  - We explored the utility of neural stem cells (NSCs) as an in vitro model for
      evaluating preclinical therapeutics in succinic semialdehyde dehydrogenase
      deficient (SSADHD) mice. NSCs were obtained from aldh5a1+/+ and aldh5a1-/- mice
      (aldh5a1 = aldehyde dehydrogenase 5a1 = SSADH). Multiple parameters were
      evaluated including: (1) production of GHB (gamma-hydroxybutyrate), the
      biochemical hallmark of SSADHD; (2) rescue from cell death with the dual mTOR
      (mechanistic target of rapamycin) inhibitor, XL-765, an agent previously shown to
      rescue aldh5a1-/- mice from premature lethality; (3) mitochondrial number, total
      reactive oxygen species, and mitochondrial superoxide production, all previously
      documented as abnormal in aldh5a1-/- mice; (4) total ATP levels and ATP
      consumption; and (5) selected gene expression profiles associated with epilepsy,
      a prominent feature in both experimental and human SSADHD. Patterns of
      dysfunction were observed in all of these parameters and mirrored earlier
      findings in aldh5a1-/- mice. Patterns of dysregulated gene expression between
      hypothalamus and NSCs centered on ion channels, GABAergic receptors, and
      inflammation, suggesting novel pathomechanisms as well as a developmental
      ontogeny for gene expression potentially associated with the murine epileptic
      phenotype. The NSC model of SSADHD will be valuable in providing a first-tier
      screen for centrally-acting therapeutics and prioritizing therapeutic concepts of
      preclinical animal studies applicable to SSADHD.

PMID- 29053745
TI  - Impact of the structural integrity of the three-way junction of adenovirus VAI
      RNA on PKR inhibition.
AB  - Highly structured RNA derived from viral genomes is a key cellular indicator of
      viral infection. In response, cells produce the interferon inducible RNA
      dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates
      eukaryotic initiation factor 2alpha and attenuates viral protein translation.
      Adenovirus can evade this line of defence through transcription of a non-coding
      RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that
      meet at a three-way junction; an apical stem responsible for the interaction with
      PKR, a central stem required for inhibition, and a terminal stem. Recent studies
      have highlighted the potential importance of the tertiary structure of the three
      way junction to PKR inhibition by enabling interaction between regions of the
      central and terminal stems. To further investigate the role of the three-way
      junction, we characterized the binding affinity and inhibitory potential of
      central stem mutants designed to introduce subtle alterations. These results were
      then correlated with small-angle X-ray scattering solution studies and
      computational tertiary structural models. Our results demonstrate that while
      mutations to the central stem have no observable effect on binding affinity to
      PKR, mutations that appear to disrupt the structure of the three-way junction
      prevent inhibition of PKR. Therefore, we propose that instead of simply
      sequestering PKR, a specific structural conformation of the PKR-VAI complex may
      be required for inhibition.

PMID- 29053746
TI  - External auditory exostoses and hearing loss in the Shanidar 1 Neandertal.
AB  - The Late Pleistocene Shanidar 1 older adult male Neandertal is known for the
      crushing fracture of his left orbit with a probable reduction in vision, the loss
      of his right forearm and hand, and evidence of an abnormal gait, as well as
      probable diffuse idiopathic skeletal hyperostosis. He also exhibits advanced
      external auditory exostoses in his left auditory meatus and larger ones with
      complete bridging across the porus in the right meatus (both Grade 3). These
      growths indicate at least unilateral conductive hearing (CHL) loss, a serious
      sensory deprivation for a Pleistocene hunter-gatherer. This condition joins the
      meatal atresia of the Middle Pleistocene Atapuerca-SH Cr.4 in providing evidence
      of survival with conductive hearing loss (and hence serious sensory deprivation)
      among these Pleistocene humans. The presence of CHL in these fossils thereby
      reinforces the paleobiological and archeological evidence for supporting social
      matrices among these Pleistocene foraging peoples.

PMID- 29053747
TI  - Establishment of pten knockout medaka with transcription activator-like effector
      nucleases (TALENs) as a model of PTEN deficiency disease.
AB  - Phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that
      antagonizes signaling by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling
      pathway. The PTEN gene is a major tumor suppressor, with mutations of this gene
      occurring frequently in tumors of humans and mice. We have now developed mutant
      medaka deficient in PTEN with the use of transcription activator-like effector
      nuclease (TALEN) technology. Medaka possesses two pten genes, ptena and ptenb,
      similar to zebrafish. We established 16 ptena mutant lines and two ptenb mutant
      lines. Homozygous single pten mutants were found to be viable and fertile. In
      contrast, pten double-knockout (dko) embryos manifested severe abnormalities in
      vasculogenesis, eye size, and tail development at 72 hours post
      fertilization(hpf) and died before hatching. Immunoblot analysis revealed that
      the ratio of phosphorylated to total forms of AKT (pAKT/AKT) in pten dko embryos
      was four times that in wild-type embryos, indicative of up-regulation of
      signaling by the PI3K-AKT pathway. Treatment of pten dko embryos with the PI3K
      inhibitor LY294002 reduced the pAKT/AKT ratio by about one-half and partially
      rescued the defect in vasculogenesis. Additional inhibitors of the PI3K-AKT
      pathway, including rapamycin and N-alpha-tosyl-L-phenylalanyl chloromethyl
      ketone, also partially restored vasculogenesis in the dko embryos. Our model
      system thus allows pten dko embryos to be readily distinguished from wild-type
      embryos at an early stage of development and is suitable for the screening of
      drugs able to compensate for PTEN deficiency.

PMID- 29053748
TI  - Treatment with the NR4A1 agonist cytosporone B controls influenza virus infection
      and improves pulmonary function in infected mice.
AB  - The transcription factor NR4A1 has emerged as a pivotal regulator of the
      inflammatory response and immune homeostasis. Although contribution of NR4A1 in
      the innate immune response has been demonstrated, its role in host defense
      against viral infection remains to be investigated. In the present study, we show
      that administration of cytosporone B (Csn-B), a specific agonist of NR4A1, to
      mice infected with influenza virus (IAV) reduces lung viral loads and improves
      pulmonary function. Our results demonstrate that administration of Csn-B to naive
      mice leads to a modest production of type 1 IFN. However, in IAV-infected mice,
      such production of IFNs is markedly increased following treatment with Csn-B. Our
      study also reveals that alveolar macrophages (AMs) appear to have a significant
      role in Csn-B effects, since selective depletion of AMs with clodronate liposome
      correlates with a marked reduction of IFN production, viral clearance and
      morbidity in IAV-infected mice. Furthermore, when reemergence of AMs is observed
      following clodronate liposome administration, an increased production of IFNs was
      detected in bronchoalveolar fluids of IAV-infected mice treated with Csn-B,
      supporting the contribution of AMs in Csn-B effects. While treatment of mice with
      Csn-B induces phosphorylation of transcriptional factors IRF3 and IRF7, the
      latter appears to be less indispensable since effects of Csn-B treatment on the
      synthesis of IFNs were slightly affected in IAV-infected mice lacking functional
      IRF7. Together, our results highlight the capacity of Csn-B and consequently of
      NR4A1 transcription factor in controlling IAV infection.

PMID- 29053749
TI  - Phylogeography and genetic effects of habitat fragmentation on endemic Urophysa
      (Ranunculaceae) in Yungui Plateau and adjacent regions.
AB  - Urophysa is a Chinese endemic genus with only two species (U. rockii and U.
      henryi) distributed in Yungui Plateau (Guizhou Province) and adjacent regions
      (i.e., Provinces of Hunan, Hubei, Chongqing and Sichuan). The aim of this study
      was to determine the genetic diversity and population differentiation within
      Urophysa and investigate the effect of the Yungui Plateau uplift and climate
      oscillations on evolution of Urophysa. In this study, micro-morphological
      characteristics, nine microsatellite loci (SSR), two nuclear loci (ITS and ETS)
      and two chloroplast fragments (psbA-trnH and trnL-trnF) were used to analyze the
      phylogenetic relationships and assess genetic and phylogeographical structure of
      Urophysa. Isolation by distance (IBD) was performed to research the effects of
      geographical isolation. We detected high genetic diversity at the species level
      but low genetic diversity within populations. Striking genetic differentiation
      (AMOVA) among populations and a significant phylogeographical structure (NST >
      GST, p < 0.01) were detected among U. henryi populations, along with significant
      effects of isolation by distance (IBD). Molecular clock estimation using
      calibration strategy and cpDNA substitution rate indicated that the divergence of
      U. henryi occurred during late Miocene to early Quaternary, when the orogeny of
      Yungui Plateau was violent. U. rockii originated at the early Quaternary and
      further differentiated at early Pleistocene. Our results suggested that habitat
      fragmentation played an important role in the genetic diversity and population
      differentiation of U. rockii and U. henryi. Heterogenous geomorphological
      configuration and complicated environment resulted from rapid uplift of the
      Yungui Plateau were inferred as important incentives for the modern
      phylogeograhpical pattern and species divergence of Urophysa. The geographical
      isolation, limited gene flow, specialized morphologies and the Pleistocene
      climatic oscillation greatly contributed to the allopatric divergence of U.
      rockii. Significant genetic drift and inbreeding were detected in these two
      species, in situ measures should be implemented to protect them.

PMID- 29053750
TI  - Middle-aged individuals with thalidomide embryopathy have undergone few surgical
      limb procedures and demonstrate a high degree of physical independence.
AB  - BACKGROUND: Thalidomide is known to have induced thalidomide embryopathy (TE) in
      more than 10,000 live-born children worldwide between 1957-1962. AIM: The aim of
      this study was to investigate the need for orthopaedic surgery and limb orthosis
      in relation to function and physical independence in middle-aged individuals with
      TE. METHODS: 13 women/18 men with a mean age of 45.8 (SD 1.1) years were
      included. Information about limb surgery, the use of orthotic devices, jobs,
      accommodation, disability adjustments and personal assistants was collected.
      Physical function was measured by a modified general function score. The time
      needed for activities of daily living (ADL) was collected. Individuals with
      proximal focal femoral deficiency, PFFD, and participants in need of home or work
      adaptations were compared with the rest of the group. RESULT: 31 surgical
      procedures had been performed in the extremities. Three individuals were in need
      of personal assistance and seven had disability-adjusted homes. 28 individuals
      were working and 24 reported participation in exercises. Those with PFFD had
      significantly lower function score and needed a significantly longer time for ADL
      in the morning (p = 0.001 and p = 0.032). The group in need of home or work
      adjustments had significantly lower function score and needed longer time for
      morning ADL (p = 0.012 and p = 0.009). DISCUSSION: Few orthopaedic procedures had
      been performed. The TE individuals except the ones with PFFD and those in the
      need of disability adjustments, were mostly active workers, reported good
      physical function and participated in exercises, despite limb malformations.

PMID- 29053751
TI  - Bacterial community analysis of anoxic/aeration (A/O) system in a combined
      process for gibberellin wastewater treatment.
AB  - Gibberellin wastewater cannot be directly discharged without treatment due to its
      high concentrations of sulfate and organic compounds and strong acidity.
      Therefore, multi-stage anaerobic bioreactor + micro-aerobic+ anoxic/aeration
      (A/O) + biological contact oxidation combined processes are used to treat
      gibberellin wastewater. However, knowledge of the treatment effects of the A/O
      process and bacterial community structure in the aeration tank reactors of such
      systems is sparse. Therefore, this study was conducted to investigate the
      treatment effects and operation of the A/O process on gibberellin wastewater, as
      well as changes in the bacterial community structure of activated sludge in the
      aeration tank during treatment. Moreover, removal was examined based on
      evaluation of effluent after A/O treatment. Although influent chemical oxygen
      demand (COD), NH3-N and total phosphorus (TP) fluctuated, effluent COD, NH3-N and
      TP remained stable. Moreover, average COD, NH3-N and TP removal efficiency were
      68.41%, 93.67% and 45.82%, respectively, during the A/O process. At the phylum
      level, Proteobacteria was the dominant phylum in all samples, followed by
      Chloroflexi, Bacteroidetes and Actinobacteria. Proteobacteria played an important
      role in the removal of organic matter. Chloroflexi was found to be responsible
      for the degradation of carbohydrates and Bacteroidetes also had been found to be
      responsible for the degradation of complex organic matters. Actinobacteria are
      able to degrade a variety of environmental chemicals. Additionally,
      Anaerolineaceae_uncultured was the major genus in samples collected on May 25,
      2015, while Novosphingobium and Nitrospira were dominant in most samples.
      Nitrosomonas are regarded as the dominant ammonia-oxidizing bacteria, while
      Nitrospira are the main nitrite-oxidizing bacteria. Bacterial community structure
      varied considerably with time, and a partial Mantel test showed a highly
      significant positive correlation between bacterial community structure and DO.
      The bacterial community structure was also positively correlated with temperature
      and SO42-.

PMID- 29053752
TI  - Rhizospheric microbial communities associated with wild and cultivated
      frankincense producing Boswellia sacra tree.
AB  - Boswellia sacra, a frankincense producing endemic tree, has been well known for
      its cultural, religious and economic values. However, the tree has been least
      explored for the associated microsymbiota in the rhizosphere. The current study
      elucidates the fungal and bacterial communities of the rhizospheric regions of
      the wild and cultivated B. sacra tree populations through next generation
      sequencing. The sequence analysis showed the existence of 1006+/-8.9 and 60.6+/
      3.1 operational taxonomic unit (OTUs) for bacterial and fungal communities
      respectively. In fungal communities, five major phyla were found with
      significantly higher abundance of Ascomycota (60.3%) in wild population and
      Basidiomycota (52%) in cultivated tree rhizospheres. Among bacterial communities,
      31 major phyla were found, with significant distribution of Actinobacteria in
      wild tree rhizospheres, whereas Proteobacteria and Acidobacteria were highly
      abundant in cultivated trees. The diversity and abundance of microbiome varied
      significantly depending upon soil characteristics of the three different
      populations. In addition, significantly higher glucosidases, cellulases and
      indole-3-acetic acid were found in cultivated tree's rhizospheres as compared to
      wild tree populations. for these plants to survive the harsh arid-land
      environmental conditions. The current study is a first comprehensive work and
      advances our knowledge about the core fungal and bacterial microbial microbiome
      associated with this economically important tree.

PMID- 29053753
TI  - 3D morphological analysis of the mouse cerebral vasculature: Comparison of in
      vivo and ex vivo methods.
AB  - Ex vivo 2-photon fluorescence microscopy (2PFM) with optical clearing enables
      vascular imaging deep into tissue. However, optical clearing may also produce
      spherical aberrations if the objective lens is not index-matched to the clearing
      material, while the perfusion, clearing, and fixation procedure may alter
      vascular morphology. We compared in vivo and ex vivo 2PFM in mice, focusing on
      apparent differences in microvascular signal and morphology. Following in vivo
      imaging, the mice (four total) were perfused with a fluorescent gel and their
      brains fructose-cleared. The brain regions imaged in vivo were imaged ex vivo.
      Vessels were segmented in both images using an automated tracing algorithm that
      accounts for the spatially varying PSF in the ex vivo images. This spatial
      variance is induced by spherical aberrations caused by imaging fructose-cleared
      tissue with a water-immersion objective. Alignment of the ex vivo image to the in
      vivo image through a non-linear warping algorithm enabled comparison of apparent
      vessel diameter, as well as differences in signal. Shrinkage varied as a function
      of diameter, with capillaries rendered smaller ex vivo by 13%, while penetrating
      vessels shrunk by 34%. The pial vasculature attenuated in vivo microvascular
      signal by 40% 300 MUm below the tissue surface, but this effect was absent ex
      vivo. On the whole, ex vivo imaging was found to be valuable for studying deep
      cortical vasculature.

PMID- 29053754
TI  - Coming of age: - Do female harbour porpoises (Phocoena phocoena) from the North
      Sea and Baltic Sea have sufficient time to reproduce in a human influenced
      environment?
AB  - The harbour porpoise is the only cetacean species native to German waters. Since
      human pressures are suggested to shorten their reproductive lifespan, basic
      knowledge on reproduction is strongly required. One parameter is the onset of
      sexual maturity in female harbour porpoises. Therefore, we investigated the first
      signs of sexual maturity for a period of almost two decades (1990-2016). Ovaries
      from 111 female harbour porpoises from the German North Sea and Baltic Sea were
      examined for the presence and morphological structure of follicles, corpora lutea
      and corpora albicantia. Based on the ovarian characteristics we performed the
      first model-based estimation of age at sexual maturity for harbour porpoises from
      German waters. Additionally, we produced a demographical age structure based on
      all female strandings and bycatches from German coasts. Our results showed that
      corpora lutea and corpora albicantia as signs of former ovulation could be found
      in individuals at an age of 4.95 (+/- 0.6) years. No significant differences
      between specimens from the North Sea and Baltic Sea were detected. However, the
      average age at death differed significantly with 5.70 (+/- 0.27) years for North
      Sea animals and 3.67 (+/- 0.30) years for those in the Baltic Sea. Growing
      evidence exists that the shortened lifespan of Baltic Sea harbour porpoises is
      linked to an anthropogenically influenced environment with rising bycatch
      mortalities due to local gillnet fisheries. Thus, our findings support the idea
      of local management plans based on a model-based detection of age at sexual
      maturity and considering the anthropogenic impacts on the population for
      effective protection of harbour porpoises and the North Sea and Baltic Sea.

PMID- 29053756
TI  - Comprehensive and comparative lipidome analysis of Vitis vinifera L. cv. Pinot
      Noir and Japanese indigenous V. vinifera L. cv. Koshu grape berries.
AB  - Vitis vinifera cv. Koshu is an indigenous grape cultivar that has been cultivated
      for more than a thousand years in Japan and one of the most important cultivars
      in white winemaking. To improve Koshu wine quality, it is necessary to identify
      the metabolites in Koshu berry. We conducted a comprehensive and comparative
      lipidome analysis of Koshu and Pinot Noir berries cultivated in the same location
      in Japan using GC-MS/MS for fatty acids and LC-MS for glycerolipids and
      glycerophospholipids. Koshu skins and juices contained 22 and 19 fatty acids,
      respectively, whereas 23 and 20 fatty acids were detected in Pinot Noir skins and
      juices. C22:6n3 and C24:0 contents in Koshu skins were two and three times higher
      than those in Pinot Noir skins. C24:0 content in Koshu juices was also higher
      than that in Pinot Noir juices. Forty-nine lipid components (six
      digalactosyldiacylglycerols, one monogalactosyldiacylglycerol, 10
      phosphatidylcholines, 12 phosphatidylethanolamines, and 20 triglycerides) were
      detected in Pinot Noir and Koshu skins. Strong peaks were observed for MGDG 36:6,
      DGDG 36:6, PC 34:2, PC 36:5, TG 54:6, TG 54:7, and TG 54:8 in Koshu skins. The
      contents of 36 of the 49 lipid components were significantly higher in Pinot Noir
      skins than Koshu skins. Pinot Noir skins contained more lipids whose alkyl chains
      have more than 18 carbons than Koshu skins. Further analysis of both lipid
      profiles revealed that the number of double bonds in a fatty acid molecule in
      Pinot Noir skins and juices was significantly larger than that in Koshu skins and
      juices. A strong relationship exists between the heat requirement of grapevine
      cultivars and the level of fatty acid desaturation. C18-fatty acids were the
      major components in Koshu and Pinot Noir berries. The expression levels of C18
      fatty acid desaturases regulated the accumulation of C18-unsaturated fatty acids
      in berry skins. The loss of C18:3 in Koshu berries at the end of ripening was
      observed. Koshu might effectively convert C18:3 into (Z)-hex-3-enal for the
      production of C6-aroma compounds. These findings by the lipidome analysis are
      expected to contribute to the improvement of Koshu wine aroma and breeding
      strategies of cold-tolerant Koshu grapevines.

PMID- 29053755
TI  - MicroRNAs expression profile in solid and unicystic ameloblastomas.
AB  - OBJECTIVES: Odontogenic tumors (OT) represent a specific pathological category
      that includes some lesions with unpredictable biological behavior. Although most
      of these lesions are benign, some, such as the ameloblastoma, exhibit local
      aggressiveness and high recurrence rates. The most common types of ameloblastoma
      are the solid/multicystic (SA) and the unicystic ameloblastoma (UA); the latter
      considered a much less aggressive entity as compared to the SA. The microRNA
      system regulates the expression of many human genes while its deregulation has
      been associated with neoplastic development. The aim of the current study was to
      determine the expression profiles of microRNAs present in the two most common
      types of ameloblastomas. MATERIAL & METHODS: MicroRNA expression profiles were
      assessed using TaqMan(r) Low Density Arrays (TLDAs) in 24 samples (8 SA, 8 UA and
      8 control samples). The findings were validated using quantitative RTqPCR in an
      independent cohort of 19 SA, 8 UA and 19 dentigerous cysts as controls. RESULTS:
      We identified 40 microRNAs differentially regulated in ameloblastomas, which are
      related to neoplastic development and differentiation, and with the osteogenic
      process. Further validation of the top ranked microRNAs revealed significant
      differences in the expression of 6 of them in relation to UA, 7 in relation to SA
      and 1 (miR-489) that was related to both types. CONCLUSION: We identified a new
      microRNA signature for the ameloblastoma and for its main types, which may be
      useful to better understand the etiopathogenesis of this neoplasm. In addition,
      we identified a microRNA (miR-489) that is suggestive of differentiating among
      solid from unicystic ameloblastoma.

PMID- 29053757
TI  - Generation of composite Persea americana (Mill.) (avocado) plants: A proof-of
      concept-study.
AB  - Avocado (Persea americana (Mill.)), an important commercial fruit, is severely
      affected by Phytophthora Root Rot in areas where the pathogen is prevalent.
      However, advances in molecular research are hindered by the lack of a high
      throughput transient transformation system in this non-model plant. In this
      study, a proof-of-concept is demonstrated by the successful application of
      Agrobacterium rhizogenes-mediated plant transformation to produce composite
      avocado plants. Two ex vitro strategies were assessed on two avocado genotypes
      (Itzamna and A0.74): In the first approach, 8-week-old etiolated seedlings were
      scarred with a sterile hacksaw blade at the base of the shoot, and in the second,
      inch-long incisions were made at the base of the shoot (20-week-old non-etiolated
      plants) with a sterile blade to remove the cortical tissue. The scarred/wounded
      shoot surfaces were treated with A. rhizogenes strains (K599 or ARqua1)
      transformed with or without binary plant transformation vectors pRedRootII
      (DsRed1 marker), pBYR2e1-GFP (GFP- green fluorescence protein marker) or
      pBINUbiGUSint (GUS- beta-glucuronidase marker) with and without rooting hormone
      (Dip 'N' Grow) application. The treated shoot regions were air-layered with
      sterile moist cocopeat to induce root formation. Results showed that hormone
      application significantly increased root induction, while Agrobacterium-only
      treatments resulted in very few roots. Combination treatments of
      hormone+Agrobacterium (-/+ plasmids) showed no significant difference. Only the
      ARqua1(+plasmid):A0.74 combination resulted in root transformants, with
      hormone+ARqua1(+pBINUbiGUSint) being the most effective treatment with ~17 and
      25% composite plants resulting from strategy-1 and strategy-2, respectively. GUS-
      and GFP-expressing roots accounted for less than 4 and ~11%, respectively, of the
      total roots/treatment/avocado genotype. The average number of transgenic roots on
      the composite plants was less than one per plant in all treatments. PCR and
      Southern analysis further confirmed the transgenic nature of the roots expressing
      the screenable marker genes. Transgenic roots showed hyper-branching compared to
      the wild-type roots but this had no impact on Phytophthora cinnamomi infection.
      There was no difference in pathogen load 7-days-post inoculation between
      transformed and control roots. Strategy-2 involving A0.74:ARqua1 combination was
      the best ex vitro approach in producing composite avocado plants. The approach
      followed in this proof-of-concept study needs further optimisation involving
      multiple avocado genotypes and A. rhizogenes strains to achieve enhanced root
      transformation efficiencies, which would then serve as an effective high
      throughput tool in the functional screening of host and pathogen genes to improve
      our understanding of the avocado-P. cinnamomi interaction.

PMID- 29053758
TI  - Sex differences in long-term mortality among acute myocardial infarction
      patients: Results from the ISAR-RISK and ART studies.
AB  - BACKGROUND: Mortality rates in females who survived acute myocardial infarction
      (AMI) exceed those in males. Differences between sexes in age, cardiovascular
      risk factors and revascularization therapy have been proposed as possible
      reasons. OBJECTIVE: To select sets of female and male patients comparable in
      respect of relevant risk factors in order to compare the sex-specific risk in a
      systematic manner. METHODS: Data of the ISAR-RISK and ART studies were
      investigated. Patients were enrolled between 1996 and 2005 and suffered from AMI
      within 4 weeks prior to enrolment. Patients of each sex were selected with 1:1
      equivalent age, previous AMI history, sinus-rhythm presence, hypertension,
      diabetes mellitus, smoking status, left ventricular ejection fraction (LVEF), and
      revascularization therapy. Survival times were compared between sex groups in the
      whole study cohort and in the matched cohort. RESULTS: Of 3840 consecutive AMI
      survivors, 994 (25.9%) were females and 2846 (74.1%) were males. Females were
      older and suffered more frequently from hypertension and diabetes mellitus. In
      the whole cohort, females showed an increased mortality with a hazard ratio (HR)
      of 1.54 compared to males (p<0.0001). The matched cohort comprised 802 patients
      of each sex and revealed a trend towards poorer survival in females (HR for
      female sex 1.14; p = 0.359). However, significant mortality differences with a
      higher risk in matched females was observed during the first year after AMI (HR =
      1.61; p = 0.045) but not during the subsequent years. CONCLUSION: Matched sub
      groups of post-AMI patients showed a comparable long-term mortality. However, a
      female excess mortality remained during first year after AMI and cannot be
      explained by differences in age, cardiovascular risk factors, and modes of acute
      treatment. Other causal factors, including clinical as well as psychological and
      social aspects, need to be considered. Female post-AMI patients should be
      followed more actively particularly during the first year after AMI.

PMID- 29053759
TI  - Molecular dynamic simulations reveal suboptimal binding of salbutamol in T164I
      variant of beta2 adrenergic receptor.
AB  - The natural variant C491T (rs1800088) in ADRB2 gene substitutes Threonine to
      Isoleucine at 164th position in beta2AR and results in receptor sequestration and
      altered binding of agonists. Present investigation pursues to identify the effect
      of T164I variation on function and structure of beta2AR through systematic
      computational approaches. The study, in addition, addresses altered binding of
      salbutamol in T164I variant through molecular dynamic simulations. Methods
      involving changes in free energy, solvent accessibility surface area, root mean
      square deviations and analysis of binding cavity revealed structural
      perturbations in receptor to incur upon T164I substitution. For comprehensive
      understanding of receptor upon substitution, OPLS force field aided molecular
      dynamic simulations were performed for 10 ns. Simulations revealed massive
      structural departure for T164I beta2AR variant from the native state along with
      considerably higher root mean square fluctuations of residues near the cavity.
      Affinity prediction by molecular docking showed two folds reduced affinity of
      salbutamol in T164I variant. To validate the credibility docking results,
      simulations for ligand-receptor complex were performed which demonstrated
      unstable salbutamol-T164I beta2AR complex formation. Further, analysis of
      interactions in course of simulations revealed reduced ligand-receptor
      interactions of salbutamol in T164I variant. Taken together, studies herein
      provide structural rationales for suboptimal binding of salbutamol in T164I
      variant through integrated molecular modeling approaches.

PMID- 29053760
TI  - Notice of Retraction. Wansink B, Just DR, Payne CR. Can Branding Improve School
      Lunches? Arch Pediatr Adolesc Med. 2012;166(10):967-968. JAMA Pediatr.
      doi:10.1001/archpediatrics.2012.999.

PMID- 29053762
TI  - Introducing Gustavo D. Aguirre, the 2017 Recipient of the Proctor Medal.

PMID- 29053761
TI  - The Transcription Factor Prdm16 Marks a Single Retinal Ganglion Cell Subtype in
      the Mouse Retina.
AB  - Purpose: Retinal ganglion cells (RGC) can be categorized into roughly 30 distinct
      subtypes. How these subtypes develop is poorly understood, in part because few
      unique subtype markers have been characterized. We tested whether the Prdm16
      transcription factor is expressed by RGCs as a class or within particular
      ganglion cell subtypes. Methods: Embryonic and mature retinal sections and
      flatmount preparations were examined by immunohistochemistry for Prdm16 and
      several other cell type-specific markers. To visualize the morphology of Prdm16+
      cells, we utilized Thy1-YFP-H transgenic mice, where a small random population of
      RGCs expresses yellow fluorescent protein (YFP) throughout the cytoplasm.
      Results: Prdm16 was expressed in the retina starting late in embryogenesis.
      Prdm16+ cells coexpressed the RGC marker Brn3a. These cells were arranged in an
      evenly spaced pattern and accounted for 2% of all ganglion cells. Prdm16+ cells
      coexpressed parvalbumin, but not calretinin, melanopsin, Smi32, or CART. This
      combination of marker expression and morphology data from Thy1-YFP-H mice
      suggested that the Prdm16+ cells represented a single ganglion cell subtype.
      Prdm16 also marked vascular endothelial cells and mural cells of retinal
      arterioles. Conclusions: A single subtype of ganglion cell appears to be uniquely
      marked by Prdm16 expression. While the precise identity of these ganglion cells
      is unclear, they most resemble the G9 subtype described by Volgyi and colleagues
      in 2009. Future studies are needed to determine the function of these ganglion
      cells and whether Prdm16 regulates their development.

PMID- 29053765
TI  - Cross-cueing cannot explain unified control in split-brain patients.

PMID- 29053764
TI  - Contribution of Calpain and Caspases to Cell Death in Cultured Monkey RPE Cells.
AB  - Purpose: AMD is the leading cause of human vision loss after 65 years of age.
      Several mechanisms have been proposed: (1) age-related failure of the choroidal
      vasculature leads to loss of RPE; (2) RPE dysfunctions due to accumulation of
      phagocytized, but unreleased A2E (N-retinylidene-N-retinylethanolamine); (3) zinc
      deficiency activation of calpain and caspase proteases, leading to cell death.
      The purpose of the present study is to compare activation of calpain and caspase
      in monkey RPE cells cultured under hypoxia or with A2E. Methods: Monkey primary
      RPE cells were cultured under hypoxic conditions in a Gaspak pouch or cultured
      with synthetic A2E. Immunoblotting was used to detect activation of calpain and
      caspase. Calpain inhibitor, SNJ-1945, and pan-caspase inhibitor, z-VAD-fmk, were
      used to confirm activation of the proteases. Results: (1) Hypoxia and A2E each
      decreased viability of RPE cells in a time-dependent manner. (2) Incubation under
      hypoxia alone induced activation of calpain, but not caspases. SNJ-1945 inhibited
      calpain activation, but z-VAD-fmk did not. (3) Incubation with A2E alone induced
      activation of calpain, caspase-9, and caspase-3. SNJ-1945 inhibited calpain
      activation. z-VAD-fmk inhibited caspase activation, suggesting no interaction
      between calpain and caspases. Conclusions: Hypoxia activated the calpain pathway,
      while A2E activated both calpain and caspase pathways in monkey RPE cells. Such
      knowledge may be utilized in the treatment of AMD if inhibitor drugs against
      calpain and/or caspase are used to prevent RPE dysfunction caused by hypoxia or
      A2E.

PMID- 29053763
TI  - Concepts and Strategies in Retinal Gene Therapy.

PMID- 29053766
TI  - TOR1A variants cause a severe arthrogryposis with developmental delay, strabismus
      and tremor.
AB  - See Ginevrino and Valente (doi:10.1093/brain/awx260) for a scientific commentary
      on this article.Autosomal dominant torsion dystonia-1 is a disease with
      incomplete penetrance most often caused by an in-frame GAG deletion (p.Glu303del)
      in the endoplasmic reticulum luminal protein torsinA encoded by TOR1A. We report
      an association of the homozygous dominant disease-causing TOR1A p.Glu303del
      mutation, and a novel homozygous missense variant (p.Gly318Ser) with a severe
      arthrogryposis phenotype with developmental delay, strabismus and tremor in three
      unrelated Iranian families. All parents who were carriers of the TOR1A variant
      showed no evidence of neurological symptoms or signs, indicating decreased
      penetrance similar to families with autosomal dominant torsion dystonia-1. The
      results from cell assays demonstrate that the p.Gly318Ser substitution causes a
      redistribution of torsinA from the endoplasmic reticulum to the nuclear envelope,
      similar to the hallmark of the p.Glu303del mutation. Our study highlights that
      TOR1A mutations should be considered in patients with severe arthrogryposis and
      further expands the phenotypic spectrum associated with TOR1A mutations.

PMID- 29053767
TI  - Characterizing and Comparing the Seasonality of Influenza-Like Illnesses and
      Invasive Pneumococcal Diseases Using Seasonal Waveforms.
AB  - The seasonalities of influenza-like illnesses (ILIs) and invasive pneumococcal
      diseases (IPDs) remain incompletely understood. Experimental evidence indicates
      that influenza-virus infection predisposes to pneumococcal disease, so that a
      correspondence in the seasonal patterns of ILIs and IPDs might exist at the
      population level. We developed a method to characterize seasonality by means of
      easily interpretable summary statistics of seasonal shape-or seasonal waveforms.
      Nonlinear mixed-effects models were used to estimate those waveforms based on
      weekly case reports of ILIs and IPDs in 5 regions spanning continental France
      from July 2000 to June 2014. We found high variability of ILI seasonality, with
      marked fluctuations of peak amplitudes and peak times, but a more conserved
      epidemic duration. In contrast, IPD seasonality was best modeled by a markedly
      regular seasonal baseline, punctuated by 2 winter peaks in late December to early
      January and January to February. Comparing ILI and IPD seasonal waveforms, we
      found indication of a small, positive correlation. Direct models regressing IPDs
      on ILIs provided comparable results, even though they estimated moderately larger
      associations. The method proposed is broadly applicable to diseases with
      unambiguous seasonality and is well-suited to analyze spatially or temporally
      grouped data, which are common in epidemiology.

PMID- 29053768
TI  - Investigating the Impact of Maternal Residential Mobility on Identifying Critical
      Windows of Susceptibility to Ambient Air Pollution During Pregnancy.
AB  - Identifying periods of increased vulnerability to air pollution during pregnancy
      with respect to the development of adverse birth outcomes can improve
      understanding of possible mechanisms of disease development and provide
      guidelines for protection of the child. Exposure to air pollution during
      pregnancy is typically based on the mother's residence at delivery, potentially
      resulting in exposure misclassification and biasing the estimation of critical
      windows of pregnancy. In this study, we determined the impact of maternal
      residential mobility during pregnancy on defining weekly exposure to particulate
      matter less than or equal to 10 MUm in aerodynamic diameter (PM10) and estimating
      windows of susceptibility to term low birth weight. We utilized data sets from 4
      Connecticut birth cohorts (1988-2008) that included information on all
      residential addresses between conception and delivery for each woman. We designed
      a simulation study to investigate the impact of increasing levels of mobility on
      identification of critical windows. Increased PM10 exposure during pregnancy
      weeks 16-18 was associated with an increased probability of term low birth
      weight. Ignoring residential mobility when defining weekly exposure had only a
      minor impact on the identification of critical windows for PM10 and term low
      birth weight in the data application and simulation study. Identification of
      critical pregnancy windows was robust to exposure misclassification caused by
      ignoring residential mobility in these Connecticut birth cohorts.

PMID- 29053769
TI  - Relationships of Variations in the Tongue Microbiota and Pneumonia Mortality in
      Nursing Home Residents.
AB  - Background: Aspiration of oral debris, containing dense oral bacteria, is a major
      cause of pneumonia in elderly adults. This study investigated the relationship
      between tongue microbiota composition and incidence of pneumonia-related deaths,
      in nursing home residents. Methods: The subjects were assessed for health
      conditions, including their tongue microbiota, at baseline. We determined tongue
      microbiota profiles by 16S ribosomal RNA gene sequencing and clustering approach.
      All subjects (n = 173) were followed prospectively for a median of 19 months to
      assess the incidence of all-cause death, including pneumonia-related death. We
      evaluated risk estimates of microbiota effects on death using multivariate Cox
      proportional hazards regression analysis. Results: Tongue microbiota were
      classified into two community types: type I was dominated by Prevotella and
      Veillonella species, while type II was dominated by Neisseria and Fusobacterium
      species. The subjects with type I microbiota exhibited a significantly greater
      risk of all-cause death (adjusted hazard ratio [aHR] = 3.79, 95% confidence
      interval [CI] = 1.38-10.39) and pneumonia-related death (aHR = 13.88, 95% CI =
      1.64-117.21), than those with type II microbiota. There was no significant
      association between microbiota type and other-cause death. Conclusions: The
      tongue microbiota type was significantly associated with an increased mortality
      risk from pneumonia in nursing home residents.

PMID- 29053771
TI  - The cerebellum in Alzheimer's disease: evaluating its role in cognitive decline.
AB  - The cerebellum has long been regarded as essential only for the coordination of
      voluntary motor activity and motor learning. Anatomical, clinical and
      neuroimaging studies have led to a paradigm shift in the understanding of the
      cerebellar role in nervous system function, demonstrating that the cerebellum
      appears integral also to the modulation of cognition and emotion. The search to
      understand the cerebellar contribution to cognitive processing has increased
      interest in exploring the role of the cerebellum in neurodegenerative and
      neuropsychiatric disorders. Principal among these is Alzheimer's disease. Here we
      review an already sizeable existing literature on the neuropathological,
      structural and functional neuroimaging studies of the cerebellum in Alzheimer's
      disease. We consider these observations in the light of the cognitive deficits
      that characterize Alzheimer's disease and in so doing we introduce a new
      perspective on its pathophysiology and manifestations. We propose an integrative
      hypothesis that there is a cerebellar contribution to the cognitive and
      neuropsychiatric deficits in Alzheimer's disease. We draw on the dysmetria of
      thought theory to suggest that this cerebellar component manifests as deficits in
      modulation of the neurobehavioural deficits. We provide suggestions for future
      studies to investigate this hypothesis and, ultimately, to establish a
      comprehensive, causal clinicopathological disease model.

PMID- 29053770
TI  - Tourette syndrome: a disorder of the social decision-making network.
AB  - Tourette syndrome is a common neurodevelopmental disorder defined by
      characteristic involuntary movements, tics, with both motor and phonic
      components. Tourette syndrome is usually conceptualized as a basal ganglia
      disorder, with an emphasis on striatal dysfunction. While considerable evidence
      is consistent with these concepts, imaging data suggest diffuse functional and
      structural abnormalities in Tourette syndrome brain. Tourette syndrome exhibits
      features that are difficult to explain solely based on basal ganglia circuit
      dysfunctions. These features include the natural history of tic expression, with
      typical onset of tics around ages 5 to 7 years and exacerbation during the peri
      pubertal years, marked sex disparity with higher male prevalence, and the
      characteristic distribution of tics. The latter are usually repetitive, somewhat
      stereotyped involuntary eye, facial and head movements, and phonations. A major
      functional role of eye, face, and head movements is social signalling. Prior work
      in social neuroscience identified a phylogenetically conserved network of
      sexually dimorphic subcortical nuclei, the Social Behaviour Network, mediating
      many social behaviours. Social behaviour network function is modulated
      developmentally by gonadal steroids and social behaviour network outputs are
      stereotyped sex and species specific behaviours. In 2011 O'Connell and Hofmann
      proposed that the social behaviour network interdigitates with the basal ganglia
      to form a greater network, the social decision-making network. The social
      decision-making network may have two functionally complementary limbs: the basal
      ganglia component responsible for evaluation of socially relevant stimuli and
      actions with the social behaviour network component responsible for the
      performance of social acts. Social decision-making network dysfunction can
      explain major features of the neurobiology of Tourette syndrome. Tourette
      syndrome may be a disorder of social communication resulting from developmental
      abnormalities at several levels of the social decision-making network. The social
      decision-making network dysfunction hypothesis suggests new avenues for research
      in Tourette syndrome and new potential therapeutic targets.

PMID- 29053772
TI  - The effect of increased alcohol availability on alcohol-related health problems
      up to the age of 42 among children exposed in utero: a natural experiment.
AB  - Aim: To examine whether exposure to increased alcohol availability in utero is
      associated with later alcohol-related health problems. Method: Register-linked
      population-based longitudinal study using data from a natural experiment setting,
      including 363 286 children born 1965-71. An experimental alcohol policy change
      was piloted in two regions of Sweden in 1967-68, where access to strong beer
      increased for 16-20 year old. Children exposed in utero to the policy change were
      compared to children born elsewhere in Sweden (excluding a border area), and to
      children born before and after the policy change. The outcome was obtained from
      the National Hospital Discharge Register using the Swedish index of alcohol
      related inpatient care. Hazard ratios (HR) with 95% confidence intervals (CI)
      were estimated by Cox regression analysis. Results: The results suggest that
      children conceived by young mothers prior to the policy change but exposed to it
      in utero had a slightly increased risk of alcohol-related health problems later
      in life (HR 1.26, 95% CI 0.94-1.68). A tendency towards an inverse association
      was found among children conceived by older mothers (HR 0.88, 95% CI 0.74-1.06).
      Conclusion: Results obtained from a natural experiment setting found no
      consistent evidence of long-term health consequences among children exposed in
      utero to an alcohol policy change. Some evidence however suggested an increased
      risk of alcohol-related health problems among the exposed children of young
      mothers.

PMID- 29053774
TI  - Plasma klotho and frailty in older adults: Findings from the InCHIANTI Study.
AB  - Background: The hormone klotho, encoded by the gene klotho, is primarily
      expressed in the kidney and choroid plexus of the brain. Higher klotho
      concentrations have been linked to better physical performance; however, it is
      unknown whether klotho relates to frailty status in older adults. Methods: Plasma
      klotho was measured in 774 participants aged >= 65 years enrolled in InCHIANTI, a
      prospective cohort study comprising Italian adults. Frailty status was assessed
      at three and six years after enrollment. Frailty was defined as presence of at
      least three out of the five criteria of unintentional weight loss, exhaustion,
      sedentariness, muscle weakness, and slow walking speed; prefrailty was defined as
      presence of one or two criteria; and robustness was defined as zero criteria. We
      assessed whether plasma klotho concentrations measured at the three-year visit
      related to frailty. Results: Each additional natural logarithm of klotho (pg/mL)
      was associated with lower odds of frailty versus robustness after adjustment for
      covariates (Odds Ratio [OR] 0.46; 95% confidence interval [CI] 0.21, 0.98; p
      value=0.045). Higher klotho was particularly associated with lower odds of
      exhaustion (OR 0.57; 95% CI 0.36, 0.89; p-value=0.014). Participants with higher
      klotho also had lower estimated odds of weight loss and weakness, but these
      findings were not statistically significant. Conclusions: Higher plasma klotho
      concentrations were associated with lower likelihoods of frailty and particularly
      exhaustion. Future studies should investigate modifiable mechanisms through which
      klotho may affect the frailty syndrome.

PMID- 29053773
TI  - Less is more: neural mechanisms underlying anomia treatment in chronic aphasic
      patients.

PMID- 29053775
TI  - Neuroinflammation and its relationship to changes in brain volume and white
      matter lesions in multiple sclerosis.
AB  - Brain magnetic resonance imaging is an important tool in the diagnosis and
      monitoring of multiple sclerosis patients. However, magnetic resonance imaging
      alone provides limited information for predicting an individual patient's
      disability progression. In part, this is because magnetic resonance imaging lacks
      sensitivity and specificity for detecting chronic diffuse and multi-focal
      inflammation mediated by activated microglia/macrophages. The aim of this study
      was to test for an association between 18 kDa translocator protein brain positron
      emission tomography signal, which arises largely from microglial activation, and
      measures of subsequent disease progression in multiple sclerosis patients. Twenty
      one patients with multiple sclerosis (seven with secondary progressive disease
      and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted
      and magnetization transfer magnetic resonance imaging at baseline and after 1
      year. Positron emission tomography scanning with the translocator protein
      radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes
      were segmented from the T1- and T2-weighted magnetic resonance imaging and
      relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a
      distribution volume ratio with respect to a caudate pseudo-reference region.
      Normal-appearing white matter distribution volume ratio at baseline was
      correlated with enlarging T2-hyperintense lesion volumes over the subsequent year
      (rho = 0.59, P = 0.01). A post hoc analysis showed that this association
      reflected behaviour in the subgroup of relapsing remitting patients (rho = 0.74,
      P = 0.008). By contrast, in the subgroup of secondary progressive patients,
      microglial activation at baseline was correlated with later progression of brain
      atrophy (rho = 0.86, P = 0.04). A regression model including the baseline normal
      appearing white matter distribution volume ratio, T2 lesion volume and normal
      appearing white matter magnetization transfer ratio for all of the patients
      combined explained over 90% of the variance in enlarging lesion volume over the
      subsequent 1 year. Glial activation in white matter assessed by translocator
      protein PET significantly improves predictions of white matter lesion enlargement
      in relapsing remitting patients and is associated with greater brain atrophy in
      secondary progressive disease over a period of short term follow-up.

PMID- 29053776
TI  - Who bears the cost of NICE public health recommendations?
AB  - Background: In the UK, NICE issues guidance on public health initiatives. Failure
      to report which sectors of the economy are affected by their implementation
      precludes the appropriate accounting for the full opportunity costs, and has the
      potential to result in erroneous decision making and inefficient budgetary
      planning. Sources of data: We reviewed all NICE public health guidances available
      at the time of research, categorizing the sector on which the cost burden of the
      public health initiatives fall and the extent to which this burden was estimated.
      Areas of agreement: The majority of guidances were determined to be associated
      with a cost burden on the NHS (n = 48) and local authorities' public health spend
      (n = 47). Areas of controversy: Explicit identification and quantification of
      cost burden by sector of the economy was reported for only eight guidances.
      Growing points: Increasing numbers of research studies are developing methods to
      robustly consider the implications of cross sector budget impacts. Areas timely
      for developing research: Future NICE guidance should report disaggregated costs
      across the sectors where they fall. Further research is needed to conceptualize
      the opportunity cost of financial burdens falling on non-health budgets before
      optimal decision making in public health is possible.

PMID- 29053777
TI  - Movement disorders with neuronal antibodies: syndromic approach, genetic
      parallels and pathophysiology.
AB  - Movement disorders are a prominent and common feature in many autoantibody
      associated neurological diseases, a group of potentially treatable conditions
      that can mimic infectious, metabolic or neurodegenerative disease. Certain
      movement disorders are likely to associate with certain autoantibodies; for
      example, the characteristic dyskinesias, chorea and dystonia associated with
      NMDAR antibodies, stiff person spectrum disorders with GAD, glycine receptor,
      amphiphysin or DPPX antibodies, specific paroxysmal dystonias with LGI1
      antibodies, and cerebellar ataxia with various anti-neuronal antibodies. There
      are also less-recognized movement disorder presentations of antibody-related
      disease, and a considerable overlap between the clinical phenotypes and the
      associated antibody spectra. In this review, we first describe the antibodies
      associated with each syndrome, highlight distinctive clinical or radiological
      'red flags', and suggest a syndromic approach based on the predominant movement
      disorder presentation, age, and associated features. We then examine the
      underlying immunopathophysiology, which may guide treatment decisions in these
      neuroimmunological disorders, and highlight the exceptional interface between
      neuronal antibodies and neurodegeneration, such as the tauopathy associated with
      IgLON5 antibodies. Moreover, we elaborate the emerging pathophysiological
      parallels between genetic movement disorders and immunological conditions, with
      proteins being either affected by mutations or targeted by autoantibodies.
      Hereditary hyperekplexia, for example, is caused by mutations of the alpha
      subunit of the glycine receptor leading to an infantile-onset disorder with
      exaggerated startle and stiffness, whereas antibodies targeting glycine receptors
      can induce acquired hyperekplexia. The spectrum of such immunological and genetic
      analogies also includes cerebellar ataxias and some encephalopathies. Lastly, we
      discuss how these pathophysiological considerations could reflect on possible
      future directions regarding antigen-specific immunotherapies or targeting the
      pathophysiological cascades downstream of the antibody effects.

PMID- 29053778
TI  - Influence of cerebrovascular disease on brain networks in prodromal and clinical
      Alzheimer's disease.
AB  - Network-sensitive neuroimaging methods have been used to characterize large-scale
      brain network degeneration in Alzheimer's disease and its prodrome. However, few
      studies have investigated the combined effect of Alzheimer's disease and
      cerebrovascular disease on brain network degeneration. Our study sought to
      examine the intrinsic functional connectivity and structural covariance network
      changes in 235 prodromal and clinical Alzheimer's disease patients with and
      without cerebrovascular disease. We focused particularly on two higher-order
      cognitive networks-the default mode network and the executive control network. We
      found divergent functional connectivity and structural covariance patterns in
      Alzheimer's disease patients with and without cerebrovascular disease.
      Alzheimer's disease patients without cerebrovascular disease, but not Alzheimer's
      disease patients with cerebrovascular disease, showed reductions in posterior
      default mode network functional connectivity. By comparison, while both groups
      exhibited parietal reductions in executive control network functional
      connectivity, only Alzheimer's disease patients with cerebrovascular disease
      showed increases in frontal executive control network connectivity. Importantly,
      these distinct executive control network changes were recapitulated in prodromal
      Alzheimer's disease patients with and without cerebrovascular disease. Across
      Alzheimer's disease patients with and without cerebrovascular disease, higher
      default mode network functional connectivity z-scores correlated with greater
      hippocampal volumes while higher executive control network functional
      connectivity z-scores correlated with greater white matter changes. In parallel,
      only Alzheimer's disease patients without cerebrovascular disease showed
      increased default mode network structural covariance, while only Alzheimer's
      disease patients with cerebrovascular disease showed increased executive control
      network structural covariance compared to controls. Our findings demonstrate the
      differential neural network structural and functional changes in Alzheimer's
      disease with and without cerebrovascular disease, suggesting that the underlying
      pathology of Alzheimer's disease patients with cerebrovascular disease might
      differ from those without cerebrovascular disease and reflect a combination of
      more severe cerebrovascular disease and less severe Alzheimer's disease network
      degeneration phenotype.

PMID- 29053780
TI  - Reaching and grasping actions and their context shape the perception of object
      size.
AB  - Humans frequently estimate the size of objects to grasp them. In fact, when
      performing an action, our perception is focused towards the visual properties of
      the object that enable us to successfully execute the action. However, the motor
      system is also able to influence perception, but only a few studies have reported
      evidence for action-induced visual perception modifications. Here, we aimed to
      look for a feature-specific perceptual modulation before and after a reaching or
      a grasping action. Human participants were instructed to either reach for or
      grasp two-dimensional bars of different size and to perform a size perceptual
      task before and after the action in two contexts: in one where they knew the
      subsequent type of movement and in the other where they did not know. We found
      significant modifications of perceived size of stimuli more pronounced after
      grasping than after reaching. The mere knowledge of the subsequent action type
      significantly affected the size perception before the movement execution, with
      consistent results in both manual and verbal reports. These data represent direct
      evidence that, in natural conditions without manipulation of visual information,
      the action type and the action context dynamically modulate size perception, by
      shaping it according to relevant information required to recognize and interact
      with objects.

PMID- 29053781
TI  - An image-computable psychophysical spatial vision model.
AB  - A large part of classical visual psychophysics was concerned with the fundamental
      question of how pattern information is initially encoded in the human visual
      system. From these studies a relatively standard model of early spatial vision
      emerged, based on spatial frequency and orientation-specific channels followed by
      an accelerating nonlinearity and divisive normalization: contrast gain-control.
      Here we implement such a model in an image-computable way, allowing it to take
      arbitrary luminance images as input. Testing our implementation on classical
      psychophysical data, we find that it explains contrast detection data including
      the ModelFest data, contrast discrimination data, and oblique masking data, using
      a single set of parameters. Leveraging the advantage of an image-computable
      model, we test our model against a recent dataset using natural images as masks.
      We find that the model explains these data reasonably well, too. To explain data
      obtained at different presentation durations, our model requires different
      parameters to achieve an acceptable fit. In addition, we show that contrast gain
      control with the fitted parameters results in a very sparse encoding of luminance
      information, in line with notions from efficient coding. Translating the standard
      early spatial vision model to be image-computable resulted in two further
      insights: First, the nonlinear processing requires a denser sampling of spatial
      frequency and orientation than optimal coding suggests. Second, the normalization
      needs to be fairly local in space to fit the data obtained with natural image
      masks. Finally, our image-computable model can serve as tool in future
      quantitative analyses: It allows optimized stimuli to be used to test the model
      and variants of it, with potential applications as an image-quality metric. In
      addition, it may serve as a building block for models of higher level processing.

PMID- 29053779
TI  - Cell-based therapeutic strategies for multiple sclerosis.
AB  - The availability of multiple disease-modifying medications with regulatory
      approval to treat multiple sclerosis illustrates the substantial progress made in
      therapy of the disease. However, all are only partially effective in preventing
      inflammatory tissue damage in the central nervous system and none directly
      promotes repair. Cell-based therapies, including immunoablation followed by
      autologous haematopoietic stem cell transplantation, mesenchymal and related stem
      cell transplantation, pharmacologic manipulation of endogenous stem cells to
      enhance their reparative capabilities, and transplantation of oligodendrocyte
      progenitor cells, have generated substantial interest as novel therapeutic
      strategies for immune modulation, neuroprotection, or repair of the damaged
      central nervous system in multiple sclerosis. Each approach has potential
      advantages but also safety concerns and unresolved questions. Moreover, clinical
      trials of cell-based therapies present several unique methodological and ethical
      issues. We summarize here the status of cell-based therapies to treat multiple
      sclerosis and make consensus recommendations for future research and clinical
      trials.

PMID- 29053782
TI  - Seizure onset zone localization using postictal hypoperfusion detected by
      arterial spin labelling MRI.
AB  - Neurological dysfunction following epileptic seizures is a well-recognized
      phenomenon. Several potential mechanisms have been suggested to explain postictal
      dysfunction, with alteration in cerebral blood flow being one possibility. These
      vascular disturbances may be long lasting and localized to brain areas involved
      in seizure generation and propagation, as supported by both animal and human
      studies. Therefore, measuring perfusion changes in the postictal period may help
      localize the seizure onset zone. Arterial spin labelling is a non-invasive, rapid
      and reproducible magnetic resonance imaging technique that measures cerebral
      perfusion. To this end, we measured postictal perfusion in patients with drug
      resistant focal epilepsy who were admitted to our seizure-monitoring unit for
      presurgical evaluation. Twenty-one patients were prospectively recruited and
      underwent arterial spin labelling scanning within 90 min of a habitual seizure.
      Patients also underwent a similar scan in the interictal period, after they were
      seizure-free for at least 24 h. The acquired scans were subtracted to identify
      the areas of significant postictal hypoperfusion. The location of the maximal
      hypoperfusion was compared to the presumed seizure onset zone to assess for
      concordance. Also, the localizing value of this technique was compared to other
      structural and functional imaging modalities. Postictal perfusion reductions of
      >15 units (ml/100 g/l) were seen in 15/21 patients (71.4%). In 12/15 (80%) of
      these patients, the location of the hypoperfusion was partially or fully
      concordant with the location of the presumed seizure onset zone. This technique
      compared favourably to other neuroimaging modalities, being similar or superior
      to structural magnetic resonance imaging in 52% of cases, ictal single-photon
      emission computed tomography in 60% of cases and interictal positron emission
      tomography in 71% of cases. Better arterial spin labelling results were obtained
      in patients in whom the seizure onset zone was discernible based on non-invasive
      data. Thus, this technique is a safe, non-invasive and relatively inexpensive
      tool to detect postictal hypoperfusion that may provide useful data to localize
      the seizure onset zone. This technique may be incorporated into the battery of
      conventional investigations for presurgical evaluation of patients with drug
      resistant focal epilepsy.

PMID- 29053783
TI  - Systematic Assessment of Multiple Routine and Near Real-Time Indicators to
      Classify the Severity of Influenza Seasons and Pandemics in the United States,
      2003-2004 Through 2015-2016.
AB  - Assessments of influenza season severity can guide public health action. We used
      the moving epidemic method to develop intensity thresholds (ITs) for 3 US
      surveillance indicators from the 2003-2004 through 2014-2015 influenza seasons
      (excluding the 2009 pandemic). The indicators were: 1) outpatient visits for
      influenza-like illness; 2) influenza-related hospitalizations; and 3) influenza-
      and pneumonia-related deaths. ITs were developed for the population overall and
      separately for children, adults, and older adults, and they were set at the upper
      limit of the 50% (IT50), 90% (IT90), and 98% (IT98) 1-sided confidence intervals
      of the geometric mean of each season's 3 highest values. Severity was classified
      as low if >=2 systems peaked below IT50, moderate if >=2 peaked between IT50 and
      IT90, high if >=2 peaked between IT90 and IT98, and very high if >=2 peaked above
      IT98. We pilot-tested this method with the 2015-2016 season and the 2009
      pandemic. Overall, 4 seasons were classified as low severity, 7 as moderate, 2 as
      high, and none as very high. Among the age groups, older adults had the most
      seasons (n = 3) classified as high, and children were the only group to have
      seasons (n = 2) classified as very high. We will apply this method to classify
      the severity of future seasons and inform pandemic response.

PMID- 29053784
TI  - Fish Intake, Genetic Predisposition to Alzheimer Disease, and Decline in Global
      Cognition and Memory in 5 Cohorts of Older Persons.
AB  - Fish are a primary source of long-chain omega-3 fatty acids, which may help delay
      cognitive aging. We pooled participants from the French Three-City study and 4 US
      cohorts (Nurses' Health Study, Women's Health Study, Chicago Health and Aging
      Project, and Rush Memory and Aging Project) for whom diet and cognitive data were
      available (n = 23,688 white persons, aged >=65 years, 88% female, baseline year
      range of 1992-1999, and median follow-up range of 3.9-9.1 years) to investigate
      the relationship of fish intake to cognitive decline and examine interactions
      with genes related to Alzheimer disease. We estimated cohort-specific
      associations between fish and change in composite scores of global cognition and
      episodic memory using linear mixed models, and we pooled results using inverse
      variance weighted meta-analysis. In multivariate analyses, higher fish intake was
      associated with slower decline in both global cognition and memory (P for trend
      <= 0.031). Consuming >=4 servings/week versus <1 serving/week of fish was
      associated with a lower rate of memory decline: 0.018 (95% confidence interval:
      0.004, 0.032) standard units, an effect estimate equivalent to that found for 4
      years of age. For global cognition, no comparisons of higher versus low fish
      intake reached statistical significance. In this meta-analysis, higher fish
      intake was associated with a lower rate of memory decline. We found no evidence
      of effect modification by genes associated with Alzheimer disease.

PMID- 29053785
TI  - Progranulin: a new avenue towards the understanding and treatment of
      neurodegenerative disease.
AB  - Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN
      gene. Progranulin consists of seven and a half, tandemly repeated, non-identical
      copies of the 12 cysteine granulin motif. Many cellular processes and diseases
      are associated with this unique pleiotropic factor that include, but are not
      limited to, embryogenesis, tumorigenesis, inflammation, wound repair,
      neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal
      dominant mutations within the GRN gene leads to frontotemporal lobar
      degeneration, a progressive neuronal atrophy that presents in patients as
      frontotemporal dementia. Frontotemporal dementia is an early onset form of
      dementia, distinct from Alzheimer's disease. The GRN-related form of
      frontotemporal lobar dementia is a proteinopathy characterized by the appearance
      of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded by
      TARDBP). The neurotrophic and neuro-immunomodulatory properties of progranulin
      have recently been reported but are still not well understood. Gene delivery of
      GRN in experimental models of Alzheimer's- and Parkinson's-like diseases inhibits
      phenotype progression. Here we review what is currently known concerning the
      molecular function and mechanism of action of progranulin in normal physiological
      and pathophysiological conditions in both in vitro and in vivo models. The
      potential therapeutic applications of progranulin in treating neurodegenerative
      diseases are highlighted.

PMID- 29053786
TI  - Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin
      resistance in neurons.
AB  - Insulin signalling deficiencies and insulin resistance have been directly linked
      to the progression of neurodegenerative disorders like Alzheimer's disease.
      However, to date little is known about the underlying molecular mechanisms or
      insulin state and distribution in the brain under pathological conditions. Here,
      we report that insulin is accumulated and retained as oligomers in
      hyperphosphorylated tau-bearing neurons in Alzheimer's disease and in several of
      the most prevalent human tauopathies. The intraneuronal accumulation of insulin
      is directly dependent on tau hyperphosphorylation, and follows the tauopathy
      progression. Furthermore, cells accumulating insulin show signs of insulin
      resistance and decreased insulin receptor levels. These results suggest that
      insulin retention in hyperphosphorylated tau-bearing neurons is a causative
      factor for the insulin resistance observed in tauopathies, and describe a novel
      neuropathological concept with important therapeutic implications.

PMID- 29053788
TI  - Tropical Rainforest and Human-Modified Landscapes Support Unique Butterfly
      Communities That Differ in Abundance and Diversity.
AB  - Tropical forests account for at least 50% of documented diversity, but
      anthropogenic activities are converting forests to agriculture and urban areas at
      an alarming rate, with potentially strong effects on insect abundance and
      diversity. However, the questions remain whether insect populations are uniformly
      affected by land conversion and if insect conservation can occur in agricultural
      margins and urban gardens. We compare butterfly populations in tropical secondary
      forests to those found in sugarcane and urban areas in coastal Guyana and
      evaluate the potential for particular butterfly communities to inhabit human
      modified landscapes. Butterflies were sampled for 1 yr using fruit-baited traps
      in three separated geographical locations on the coast. We used nonmetric
      multidimensional scaling to assess differences in species assemblages and a
      generalized linear mixed model to evaluate abundance, species richness, evenness,
      and diversity. The secondary forests in all three locations supported higher
      butterfly abundance and diversity than other human-modified areas, although the
      magnitude of this effect varied by season and location. However, each land use
      supported its own type of butterfly community, as species composition was
      different across the three land uses. Sugarcane field margins and urban gardens
      supported populations of butterflies rarely found in our tropical secondary
      forest sites. Land management practices that encourage forest conservation along
      with butterfly-friendly activities in human settlements and agricultural areas
      could improve butterfly conservation. To this end, butterfly conservation in
      Guyana and other tropical landscapes would benefit from a shift from
      inadvertently to actively making the landscape attractive for butterflies.

PMID- 29053787
TI  - Humanized mutant FUS drives progressive motor neuron degeneration without
      aggregation in 'FUSDelta14' knockin mice.
AB  - Mutations in FUS are causative for amyotrophic lateral sclerosis with a dominant
      mode of inheritance. In trying to model FUS-amyotrophic lateral sclerosis (ALS)
      in mouse it is clear that FUS is dosage-sensitive and effects arise from
      overexpression per se in transgenic strains. Novel models are required that
      maintain physiological levels of FUS expression and that recapitulate the human
      disease-with progressive loss of motor neurons in heterozygous animals. Here, we
      describe a new humanized FUS-ALS mouse with a frameshift mutation, which fulfils
      both criteria: the FUS Delta14 mouse. Heterozygous animals express mutant
      humanized FUS protein at physiological levels and have adult onset progressive
      motor neuron loss and denervation of neuromuscular junctions. Additionally, we
      generated a novel antibody to the unique human frameshift peptide epitope,
      allowing specific identification of mutant FUS only. Using our new FUSDelta14 ALS
      mouse-antibody system we show that neurodegeneration occurs in the absence of FUS
      protein aggregation. FUS mislocalization increases as disease progresses, and
      mutant FUS accumulates at the rough endoplasmic reticulum. Further,
      transcriptomic analyses show progressive changes in ribosomal protein levels and
      mitochondrial function as early disease stages are initiated. Thus, our new
      physiological mouse model has provided novel insight into the early pathogenesis
      of FUS-ALS.

PMID- 29053789
TI  - Voodoo surgery? The distinct challenges of functional neuroimaging in clinical
      neurology.

PMID- 29053790
TI  - The Hippo Signaling Pathway in Pancreatic beta-Cells: Functions and Regulations.
AB  - Hippo signaling is an evolutionarily conserved pathway that critically regulates
      development and homeostasis of various tissues in response to a wide range of
      extracellular and intracellular signals. As an emerging important player in many
      diseases, the Hippo pathway is also involved in the pathophysiology of diabetes
      on the level of the pancreatic islets. Multiple lines of evidence uncover the
      importance of Hippo signaling in pancreas development as well as in the
      regulation of beta-cell survival, proliferation, and regeneration. Hippo
      therefore represents a potential target for therapeutic agents designed to
      improve beta-cell function and survival in diabetes. In this review, we summarize
      recent data on the regulation of the Hippo signaling pathway in the pancreas/in
      pancreatic islets, its functions on beta-cell homeostasis in physiology and
      pathophysiology, and its contribution toward diabetes progression. The current
      knowledge related to general mechanisms of action and the possibility of
      exploiting the Hippo pathway for therapeutic approaches to block beta-cell
      failure in diabetes is highlighted.

PMID- 29053791
TI  - Pharmacological targeting of apelin impairs glioblastoma growth.
AB  - Glioblastoma are highly aggressive brain tumours that are associated with an
      extremely poor prognosis. Within these tumours exists a subpopulation of highly
      plastic self-renewing cancer cells that retain the ability to expand ex vivo as
      tumourspheres, induce tumour growth in mice, and have been implicated in radio-
      and chemo-resistance. Although their identity and fate are regulated by external
      cues emanating from endothelial cells, the nature of such signals remains
      unknown. Here, we used a mass spectrometry proteomic approach to characterize the
      factors released by brain endothelial cells. We report the identification of the
      vasoactive peptide apelin as a central regulator for endothelial-mediated
      maintenance of glioblastoma patient-derived cells with stem-like properties.
      Genetic and pharmacological targeting of apelin cognate receptor abrogates apelin
      and endothelial-mediated expansion of glioblastoma patient-derived cells with
      stem-like properties in vitro and suppresses tumour growth in vivo. Functionally,
      selective competitive antagonists of apelin receptor were shown to be safe and
      effective in reducing tumour expansion and lengthening the survival of
      intracranially xenografted mice. Therefore, the apelin/apelin receptor signalling
      nexus may operate as a paracrine signal that sustains tumour cell expansion and
      progression, suggesting that apelin is a druggable factor in glioblastoma.

PMID- 29053794
TI  - Corrigendum.

PMID- 29053793
TI  - 2017 Infectious Diseases Society of America Infectious Diarrhea Guidelines: A
      View From the Clinical Laboratory.

PMID- 29053795
TI  - Rare finding in Takayasu arteritis.

PMID- 29053792
TI  - 2017 Infectious Diseases Society of America Clinical Practice Guidelines for the
      Diagnosis and Management of Infectious Diarrhea.
AB  - These guidelines are intended for use by healthcare professionals who care for
      children and adults with suspected or confirmed infectious diarrhea. They are not
      intended to replace physician judgement regarding specific patients or clinical
      or public health situations. This document does not provide detailed
      recommendations on infection prevention and control aspects related to infectious
      diarrhea.

PMID- 29053797
TI  - Genotype-phenotype correlation in ATAD3A deletions: not just of scientific
      relevance.

PMID- 29053796
TI  - Exome sequencing and network analysis identifies shared mechanisms underlying
      spinocerebellar ataxia.
AB  - The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias
      in genetic nomenclature, are a rare group of progressive neurodegenerative
      disorders characterized by loss of balance and coordination. Despite the
      identification of numerous disease genes, a substantial number of cases still
      remain without a genetic diagnosis. Here, we report five novel spinocerebellar
      ataxia genes, FAT2, PLD3, KIF26B, EP300, and FAT1, identified through a
      combination of exome sequencing in genetically undiagnosed families and targeted
      resequencing of exome candidates in a cohort of singletons. We validated almost
      all genes genetically, assessed damaging effects of the gene variants in cell
      models and further consolidated a role for several of these genes in the
      aetiology of spinocerebellar ataxia through network analysis. Our work links
      spinocerebellar ataxia to alterations in synaptic transmission and transcription
      regulation, and identifies these as the main shared mechanisms underlying the
      genetically diverse spinocerebellar ataxia types.

PMID- 29053800
TI  - Reply: Genotype-phenotype correlation in ATAD3A deletions: not just of scientific
      relevance.

PMID- 29053798
TI  - In vivo characterization of cortical and white matter neuroaxonal pathology in
      early multiple sclerosis.
AB  - Neuroaxonal pathology is a main determinant of disease progression in multiple
      sclerosis; however, its underlying pathophysiological mechanisms, including its
      link to inflammatory demyelination and temporal occurrence in the disease course
      are still unknown. We used ultra-high field (7 T), ultra-high gradient strength
      diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to
      characterize microstructural changes in myelin and neuroaxonal integrity in the
      cortex and white matter in early stage multiple sclerosis, their distribution in
      lesional and normal-appearing tissue, and their correlations with neurological
      disability. Twenty-six early stage multiple sclerosis subjects (disease duration
      <=5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging
      for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging
      and neurite orientation dispersion and density imaging for assessing
      microstructural myelin, axonal and dendrite integrity in lesional and normal
      appearing tissue of the cortex and the white matter. Conventional mean
      diffusivity and fractional anisotropy metrics were also assessed for comparison.
      Cortical lesions were identified in 92% of early multiple sclerosis subjects and
      they were characterized by lower intracellular volume fraction (P = 0.015 by
      paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples
      Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related
      samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing
      cortex. Similar findings were observed in white matter lesions relative to normal
      appearing white matter (all P < 0.001), accompanied by an increased orientation
      dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P <
      0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent
      underlying fibre orientation. Additionally, the normal-appearing white matter in
      multiple sclerosis subjects had diffusely lower intracellular volume fractions
      than the white matter in controls (P = 0.029 by unpaired t-test). Cortical
      thickness did not differ significantly between multiple sclerosis subjects and
      controls. Higher orientation dispersion in the left primary motor-somatosensory
      cortex was associated with increased Expanded Disability Status Scale scores in
      surface-based general linear modelling (P < 0.05). Microstructural pathology was
      frequent in early multiple sclerosis, and present mainly focally in cortical
      lesions, whereas more diffusely in white matter. These results suggest early
      demyelination with loss of cells and/or cell volumes in cortical and white matter
      lesions, with additional axonal dispersion in white matter lesions. In the
      cortex, focal lesion changes might precede diffuse atrophy with cortical
      thinning. Findings in the normal-appearing white matter reveal early axonal
      pathology outside inflammatory demyelinating lesions.

PMID- 29053799
TI  - Erythropoietin Induces Homeostatic Plasticity at Hippocampal Synapses.
AB  - The cytokine erythropoietin (EPO) is the master regulator of erythropoiesis.
      Intriguingly, many studies have shown that the cognitive performance of patients
      receiving EPO for its hematopoietic effects is enhanced, which prompted the
      growing interest in the use of EPO-based strategies to treat neuropsychiatric
      disorders. EPO plays key roles in brain development and maturation, but also
      modulates synaptic transmission. However, the mechanisms underlying the latter
      have remained elusive. Here, we show that acute (40-60 min) exposure to EPO
      presynaptically downregulates spontaneous and afferent-evoked excitatory
      transmission, without affecting basal firing of action potentials. Conversely,
      prolonged (3 h) exposure to EPO, if followed by a recovery period (1 h), is able
      to elicit a homeostatic increase in excitatory spontaneous, but not in evoked,
      synaptic transmission. These data lend support to the emerging view that
      segregated pathways underlie spontaneous and evoked neurotransmitter release.
      Furthermore, we show that prolonged exposure to EPO facilitates a form of
      hippocampal long-term potentiation that requires noncanonical recruitment of
      calcium-permeable AMPA receptors for its maintenance. These findings provide
      important new insight into the mechanisms by which EPO enhances neuronal
      function, learning, and memory.

PMID- 29053801
TI  - Parathyroid Hormone-Related Protein-Induced Hypercalcemia of Pregnancy
      Successfully Reversed by a Dopamine Agonist.
AB  - Context: Parathyroid hormone-related protein (PTH-rP)-induced hypercalcemia or
      pseudophyperparathyroidism during pregnancy is a condition that can result in
      serious fetal and maternal complications. Among others, breast tissue might be
      the cause of this PTH-rP production, in which case medical treatment is possible,
      as we describe in this case. Setting: A 32-year-old woman presented in the 15th
      week of pregnancy with massive enlargement of breasts and abdominal pain due to
      severe hypercalcemia, hypercalciuria, and suppressed PTH. Hematological and solid
      malignancy were excluded. PTH-rP was found to be fourfold to eightfold increased,
      which is pathological even for pregnancy term. PTH-rP is produced in mammarian
      tissue as well as in placental tissue, in reaction to prolactin receptor
      activation. Prolactin hypersensitivity of breast tissue can cause excessive PTH
      rP production during pregnancy. Intervention: Dopamine agonists were applied to
      decrease prolactin. Results: Calcium levels normalized, and PTH-rP levels became
      undetectable with bromocriptin treatment. A full-term healthy baby was born
      without disorders of calcium homeostasis, neither directly after birth nor 2
      years after follow-up. After delivery, dopamine agonists could be tapered without
      recurrence of hypercalcemia. Conclusion: Pseudohyperparathyroidism of pregnancy
      was caused by increased sensitivity of mammarian tissue for prolactin, which
      could be treated medically, preventing emergency mastectomy.

PMID- 29053803
TI  - Effect of Radiation on Sucrose Detection Thresholds of Mice.
AB  - Radiotherapy is one of the most common treatments for head and neck cancers, with
      an almost obligate side effect of altered taste (Conger AD. 1973. Loss and
      recovery of taste acuity in patients irradiated to the oral cavity. Radiat Res.
      53:338-347.). In mice, targeted irradiation of the head and neck causes transient
      repression of proliferation of basal epithelial cells responsible for taste cell
      replacement, leading to a temporary depletion of taste sensory cells within taste
      buds, including Type II taste cells involved in detection of sweet stimuli
      (Nguyen HM, Reyland ME, Barlow LA. 2012. Mechanisms of taste bud cell loss after
      head and neck irradiation. J Neurosci. 32:3474-3484.). These findings suggest
      that irradiation may elevate sucrose detection thresholds, peaking at 7 days
      postirradiation when loss of Type II cells is greatest. To test this hypothesis,
      sucrose detection thresholds (concentration detected in 50% of presentations)
      were measured in mice for 15 days after treatment of: 1) irradiation while
      anesthetized, 2) anesthetic alone, or 3) saline. Mice were trained to distinguish
      water from several concentrations of sucrose. Mice were irradiated with one 8 Gy
      dose (RADSOURCE-2000 X-ray Irradiator) to the nose and mouth while under 2,2,2
      tribromethanol anesthesia (Avertin). Unexpectedly, mice given anesthesia showed a
      small elevation in sucrose thresholds compared to saline-injected mice, but
      irradiated mice show significantly elevated sucrose thresholds compared to either
      control group, an effect that peaked at 6-8 days postirradiation. The timing of
      loss and recovery of sucrose sensitivity generally coincides with the reported
      maximal reduction and recovery of Type II taste cells (Nguyen HM, Reyland ME,
      Barlow LA. 2012. Mechanisms of taste bud cell loss after head and neck
      irradiation. J Neurosci. 32:3474-3484.). Thus, even a single dose of irradiation
      can significantly alter detection of carbohydrates, an important consideration
      for patients undergoing radiotherapy.

PMID- 29053804
TI  - Reply: MRI findings of visual system alterations in Parkinson's disease.

PMID- 29053802
TI  - Docosahexaenoic Acid Supplementation in Pregnancy Modulates Placental Cellular
      Signaling and Nutrient Transport Capacity in Obese Women.
AB  - Context: Maternal obesity in pregnancy has profound impacts on maternal
      metabolism and promotes placental nutrient transport, which may contribute to
      fetal overgrowth in these pregnancies. The fatty acid docosahexaenoic acid (DHA)
      has bioactive properties that may improve outcomes in obese pregnant women by
      modulating placental function. Objective: To determine the effects of DHA
      supplementation in obese pregnant women on maternal metabolism and placental
      function. Design: Pregnant women were supplemented with DHA or placebo. Maternal
      fasting blood was collected at 26 and 36 weeks' gestation, and placentas were
      collected at term. Setting: Academic health care institution. Subjects: Thirty
      eight pregnant women with pregravid body mass index >=30 kg/m2. Intervention: DHA
      (800 mg, algal oil) or placebo (corn/soy oil) daily from 26 weeks to term. Main
      Outcomes: DHA content of maternal erythrocyte and placental membranes, maternal
      fasting blood glucose, cytokines, metabolic hormones, and circulating lipids were
      determined. Insulin, mTOR, and inflammatory signaling were assessed in placental
      homogenates, and nutrient transport capacity was determined in isolated
      syncytiotrophoblast plasma membranes. Results: DHA supplementation increased
      erythrocyte (P < 0.0001) and placental membrane DHA levels (P < 0.0001) but did
      not influence maternal inflammatory status, insulin sensitivity, or lipids. DHA
      supplementation decreased placental inflammation, amino acid transporter
      expression, and activity (P < 0.01) and increased placental protein expression of
      fatty acid transporting protein 4 (P < 0.05). Conclusions: Maternal DHA
      supplementation in pregnancy decreases placental inflammation and differentially
      modulates placental nutrient transport capacity and may mitigate adverse effects
      of maternal obesity on placental function.

PMID- 29053805
TI  - Longitudinal measures of deformation are associated with a composite measure of
      contractility derived from pressure-volume loop analysis in children.
AB  - Aims: The relationship between echocardiographic measures of left ventricular
      (LV) systolic function and reference-standard measures have not been assessed in
      children. The objective of this study was to assess the validity of
      echocardiographic indices of LV systolic function via direct comparison to a
      novel composite measure of contractility derived from pressure-volume loop (PVL)
      analysis. Methods and results: Children with normal loading conditions undergoing
      routine left heart catheterization were prospectively enrolled. PVLs were
      obtained via conductance catheters. A composite invasive composite contractility
      index (ICCI) was developed using data reduction strategies to combine four
      measures of contractility derived from PVL analysis. Echocardiograms were
      performed immediately after PVL analysis under the same anesthetic conditions.
      Conventional and speckle-tracking echocardiographic measures of systolic function
      were measured. Of 24 patients, 18 patients were heart transplant recipients, 6
      patients had a small patent ductus arteriosus or small coronary fistula. Mean age
      was 9.1 +/- 5.6 years. Upon multivariable regression, longitudinal strain was
      associated with ICCI (beta = -0.54, P = 0.02) while controlling for indices of
      preload, afterload, heart rate, and LV mass under baseline conditions. Ejection
      fraction and shortening fraction were associated with LV mass and load indices,
      but not contractility. Conclusion: Speckle-tracking derived longitudinal strain
      is associated ICCI in children with normal loading conditions. Longitudinal
      measures of deformation appear to accurately assess LV contractility in children.

PMID- 29053806
TI  - Independent Association of Plasma Hydroxysphingomyelins With Physical Function in
      the Atherosclerosis Risk in Communities (ARIC) Study.
AB  - Background: Plasma metabolites such as phosphatidylcholines and sphingomyelins
      (SMs) are associated with an age-related cognitive decline. However, their
      relations to age-related physical function decline remain largely unknown.
      Methods: We examined the cross-sectional relations of 12 plasma metabolites
      (including four phosphatidylcholines and four SMs) with physical function in 383
      older adults in the At herosclerosis Risk in Communities Study at the fifth exam
      (2011-2013, mean age [standard deviation (SD)]: 78.0 [5.5], 54.4% women, 28.3%
      African Americans). Physical function was assessed using grip strength, Short
      Physical Performance Battery, and 4-m walking speed. Individual metabolites were
      log-transformed and standardized. Multivariable linear regression was performed
      to account for demographics, APOE genotype, cardiovascular risk factors,
      comorbidities, use of antihypertensive and lipid-lowering medications, depressive
      symptoms, and cognition. Results: Lower concentrations of asymmetric
      dimethylarginine and higher concentrations of SM (OH) C22:1, SM (OH) C22:2, and
      SM (OH) C24:1 were associated with physical function measures. In particular, SM
      (OH) C22:1 and SM (OH) C24:1 were associated with all three measures of physical
      function: beta-coefficients (95% confidence interval) with grip strength were
      0.89 kg (0.00, 1.78) and 0.86 kg (0.10, 1.61) per 1 SD higher concentration,
      respectively; with Short Physical Performance Battery score, were 0.61 (0.34,
      0.88) and 0.41 (0.19, 0.63) per 1 SD difference, respectively; with 4-m walking
      speed were 0.035 m/s (0.013, 0.056) and 0.035 m/s (0.028, 0.047), respectively.
      Conclusions: Plasma SM (OH)s may be independently associated with physical
      function in older adults.

PMID- 29053807
TI  - Systematic review of the concentrations of oligosaccharides in human milk.
AB  - Context: Oligosaccharides are the third largest solid component in human milk.
      These diverse compounds are thought to have numerous beneficial functions in
      infants, including protection against infectious diseases. The structures of more
      than 100 oligosaccharides in human milk have been elucidated so far. Objective:
      The aim of this review was to identify the main factors that affect the
      concentrations of oligosaccharides in human milk and to determine whether it is
      possible to calculate representative and reliable mean concentrations. Data
      Sources: A comprehensive literature search on oligosaccharide concentrations in
      human milk was performed in 6 electronic databases: BIOSIS, Current Contents
      Search, Embase, Lancet Titles, MEDLINE and PubMed. Study Selection: The initial
      search resulted in 1363 hits. After the elimination of duplicates, the literature
      was screened. The application of strict inclusion criteria resulted in 21
      articles selected. Data Extraction: Oligosaccharide concentrations, both mean
      values and single values, reported in the literature were sorted by gestational
      age, secretor status of mothers, and defined lactation periods. Results: Mean
      concentrations, including confidence limits, of 33 neutral and acidic
      oligosaccharides reported could be calculated. Concentrations of oligosaccharides
      in human milk show variations that are dependent on both the secretor type of the
      mother and the lactation period as examined by analyses of variance. In addition,
      large interlaboratory variations in the data were observed. Conclusions:
      Worldwide interlaboratory quantitative analyses of identical milk samples would
      be required to identify the most reliable methods of determining concentrations
      of oligosaccharides in human milk. The data presented here contribute to the
      current knowledge about the composition and quantities of oligosaccharides in
      human milk and may foster greater understanding of the biological functions of
      these compounds.

PMID- 29053808
TI  - The Impact of Supplemental Antioxidants on Visual Function in Nonadvanced Age
      Related Macular Degeneration: A Head-to-Head Randomized Clinical Trial.
AB  - Purpose: The purpose of this study was to evaluate the impact of supplemental
      macular carotenoids (including versus not including meso-zeaxanthin) in
      combination with coantioxidants on visual function in patients with nonadvanced
      age-related macular degeneration. Methods: In this study, 121 participants were
      randomly assigned to group 1 (Age-Related Eye Disease Study 2 formulation with a
      low dose [25 mg] of zinc and an addition of 10 mg meso-zeaxanthin; n = 60) or
      group 2 (Age-Related Eye Disease Study 2 formulation with a low dose [25 mg] of
      zinc; n = 61). Visual function was assessed using best-corrected visual acuity,
      contrast sensitivity (CS), glare disability, retinal straylight, photostress
      recovery time, reading performance, and the National Eye Institute Visual
      Function Questionnaire-25. Macular pigment was measured using customized
      heterochromatic flicker photometry. Results: There was a statistically
      significant improvement in the primary outcome measure (letter CS at 6 cycles per
      degree [6 cpd]) over time (P = 0.013), and this observed improvement was
      statistically comparable between interventions (P = 0.881). Statistically
      significant improvements in several secondary outcome visual function measures
      (letter CS at 1.2 and 2.4 cpd; mesopic and photopic CS at all spatial
      frequencies; mesopic glare disability at 1.5, 3, and 6 cpd; photopic glare
      disability at 1.5, 3, 6, and 12 cpd; photostress recovery time; retinal
      straylight; mean and maximum reading speed) were also observed over time (P <
      0.05, for all), and were statistically comparable between interventions (P >
      0.05, for all). Statistically significant increases in macular pigment at all
      eccentricities were observed over time (P < 0.0005, for all), and the degree of
      augmentation was statistically comparable between interventions (P > 0.05).
      Conclusions: Antioxidant supplementation in patients with nonadvanced age-related
      macular degeneration results in significant increases in macular pigment and
      improvements in CS and other measures of visual function. (Clinical trial,
      http://www.isrctn.com/ISRCTN13894787).

PMID- 29053809
TI  - Comparative effects of two multi-enzyme combinations and a Bacillus probiotic on
      growth performance, digestibility of energy and nutrients, disappearance of non
      starch polysaccharides, and gut microflora in broiler chickens.
AB  - The efficacy of two exogenous enzyme combinations and a multi-strain Bacillus
      probiotic (DFM) on the growth performance, nutrient digestibility, disappearance
      of non-starch polysaccharides (NSP) and gut microbial composition was
      investigated in broilers. One-day old Ross 308 chicks were assigned to 36 pens
      with 22 birds/pen and 6 pens/treatment (Experiment 1) or 36 cages with 8
      birds/cage and 6 cages/treatment (Experiment 2). Treatment additives were added
      to nutritionally complete corn/soy based starter (d 1 to 21) and finisher (d 22
      to 42) diets. Treatments included 1) a control diet containing 500 FTU/kg phytase
      (CTL), 2) CTL + xylanase (2,000 U/kg) and amylase (200 U/kg; XA), 3) CTL+XA +
      protease (4000 U/g; XAP), 4) CTL+DFM (150,000 cfu/g of 3 strains of Bacillus
      spp), 5) CTL+DFM+XA, and 6) CTL+DFM+XAP. Supplementation with DFM increased BW,
      BWG, and FI compared with the CTL (P < 0.05); XAP, but not XA, resulted in
      increased final BW, BWG and FI compared to the control (P < 0.05). XA and XAP
      improved apparent ileal digestibility (AID) of starch and fat on d 22 to 42 with
      XAP improving AMEn (by ~82 kcal) compared with CTL birds (P < 0.01). DFM+XAP
      improved apparent ileal digestible energy (AIDE), AID of fat and starch on d 22
      to 42, and additionally had a greater than additive effect on AIDE and AMEn.
      Supplementation with DFM+XAP reduced the ileal and total tract flow of insoluble
      arabinose and additionally total tract flow of soluble and insoluble xylose and
      total galactose (P < 0.05); similar effects of XA+DFM were not seen or were lower
      in magnitude, suggesting that the protease component plays an important role in
      increasing the availability of NSP for hydrolysis. Supplementation with DFM alone
      did not affect gut bacterial populations, but XA and XAP reduced numbers of
      Campylobacter species (by > 2.5 log cfu/g; P < 0.001) and Bacteroides (P < 0.02)
      in the cecum compared with CTL birds.

PMID- 29053811
TI  - Effects of the supplemental chromium form on performance and oxidative stress in
      broilers exposed to heat stress.
AB  - This experiment was conducted to investigate effects of the organic complex form
      of supplemental chromium (Cr) on performance, oxidative stress markers, and serum
      profile in broilers exposed to heat stress (HS). A total of 1,200 10-day-old
      boilers (Ross-308) was divided into one of the 6 treatments (2 environmental
      temperatures x 3 diets with different Cr forms). The birds were kept in
      temperature-controlled rooms at either 22 +/- 2 degrees C 24 h/d (thermoneutral,
      TN group) or 34 +/- 2 degrees C for 8 h/d, 08:00 to 17:00 h, followed by 22
      degrees C for 16 h (HS group) and fed either a basal diet (C) or the basal diet
      supplemented with Cr (200 MUg/kg) through 1.600 mg of CrPic (12.43% Cr) and 0.788
      mg of CrHis (25.22% Cr). Feed intake and body weight were recorded weekly. After
      cervical dislocation, liver samples were harvested to analyze Cr concentration
      and glucose transporter-2,4 (GLUT-2,4) expression. The breast meat also was
      sampled for the concentration of Cr and expressions of nuclear factor erythroid 2
      related factor 2 (Nrf2) and nuclear factor kappa B (NF-kappaB). Data were
      analyzed by 2-way ANOVA. Heat stress caused depressions in feed intake (12.1%)
      and weight gain (21.1%) as well as elevations in feed conversion (11.2%) and
      abdominal fat (32.8%). It was also associated with depletion of Cr reserves and
      increases in serum concentrations of glucose, cholesterol, creatine, and enzymes.
      Exposure to HS was accompanied by suppression of the expressions of Nrf2 and GLUT
      2 in muscle and GLUT-4 in the liver and amplification of the expression of NF
      kappaB in muscle. Both Cr sources partially alleviated detrimental effects of HS
      on performance and metabolic profile. The efficacy of Cr as CrHis was more
      notable than Cr as CrPic, which could be attributed to higher bioavailability. In
      conclusion, CrHis can be added into the diet of broilers during hot seasons to
      overcome deteriorations in performance and wellbeing related to oxidative stress.

PMID- 29053810
TI  - Associations Between Cellular Aging Markers and Metabolic Syndrome: Findings From
      the CARDIA Study.
AB  - Background: Metabolic syndrome (MetS) is thought to promote biological aging,
      which might lead to cardiovascular and aging-related complications. This large
      scale study investigated longitudinal relationships between MetS, its components,
      and cellular aging markers: leukocyte mitochondrial DNA copy number (mtDNAcn) and
      telomere length (TL). Methods: We included 989 participants from the Coronary
      Artery Risk Development in Young Adults Study. MtDNAcn [study year (Y) 15, Y25]
      and TL (Y15, Y20, Y25) were measured via quantitative polymerase chain reaction.
      MetS components [waist circumference, triglycerides, high-density lipoprotein
      (HDL) cholesterol, systolic blood pressure, and fasting glucose] were determined
      (Y15, Y20, Y25). Generalized estimated equation and linear regression models,
      adjusting for sociodemographics and lifestyle, were used to examine associations
      between MetS and cellular aging at all time points, baseline MetS and 10-year
      changes in cellular aging, baseline cellular aging and 10-year changes in MetS,
      and 10-year changes in MetS and 10-year changes in cellular aging. Results:
      MtDNAcn and TL were negatively associated with age [mtDNAcn unstandardized beta
      (B) = -4.76; P < 0.001; TL B = -51.53; P < 0.001] and positively correlated (r =
      0.152; P < 0.001). High triglycerides were associated with low mtDNAcn and low
      HDL cholesterol with short TL. Greater Y15 waist circumference (B = -7.23; P =
      0.05), glucose (B = -13.29; P = 0.001), number of metabolic dysregulations (B = 
      7.72; P = 0.02), and MetS (B = -28.86; P = 0.006) predicted greater 10-year
      decrease in mtDNAcn but not TL. The 10-year increase in waist circumference was
      associated with 10-year telomere attrition (B = -27.61; P = 0.04). Conclusions:
      Our longitudinal data showed that some metabolic dysregulations were associated
      with mtDNAcn and TL decreases, possibly contributing to accelerated cellular
      aging but not the converse.

PMID- 29053812
TI  - Efficacy of feed additives to reduce the effect of naturally occurring mycotoxins
      fed to turkey hen poults reared to 6 weeks of age.
AB  - Corn with naturally occurring aflatoxin (AF), wheat with naturally occurring
      doxynivalenol (DON), and barley with naturally occurring zearalenone (ZEA) were
      used to make rations for feeding turkey hen poults to 6 weeks of age. Control
      rations with equal amounts of corn, wheat, and barley were also fed. The control
      rations did contain some DON while both sets of rations contained ZEA. Within
      each grain source, there were 4 treatments: the control ration plus 3 rations
      each with a different feed additive which were evaluated for the potential to
      lessen potential mycotoxin effects on bird performance and physiology. The
      additives were Biomin BioFix (2 lb/ton), Kemin Kallsil (4 lb/ton), and Nutriad
      UNIKE (3 lb/ton). The mycotoxin rations reduced poult body weight (2.31 vs. 2.08
      +/- 0.02 kg) and increased (worsened) poult feed conversion (1.47 vs. 1.51 +/-
      0.01) at 6 wk. Feeding the poults the mycotoxin feed also resulted in organ and
      physiological changes typical of feeding dietary aflatoxin although a combined
      effect of AF, DON, and ZEA which cannot be dismissed. The feed additives resulted
      in improved feed conversion to 6 wk in both grain treatment groups. The observed
      physiological effect of feeding the additives was to reduce relative gizzard
      weight for both groups and to lessen the increase in relative kidney weight for
      the birds fed the mycotoxin feed. In conclusion, the feed additives used in this
      study did alleviate the effect of dietary mycotoxins to some degree, especially
      with respect to feed conversion. Further studies of longer duration are
      warranted.

PMID- 29053813
TI  - Comparative transcriptomic analysis of high and low egg-producing duck ovaries.
AB  - The egg-laying rate is an important indicator of egg production of laying ducks.
      Egg production directly impacts the economic benefits of the duck industry. In
      order to obtain better insight into the molecular mechanisms associated with the
      process of egg production, comparative transcriptomic analysis of the ovaries of
      Jinding ducks with high and low egg production was performed using the Illumina
      HiSeq 2500 system. A total of 843 differentially expressed genes (DEGs) was
      identified, 367 that were down-regulated and 476 that were up-regulated in high
      egg production (HEP) ovaries, as compared with low egg production (LEP) ovaries.
      Some genes, such as MC5R, APOD, ORAI1, and DYRK4, were more active in HEP
      ovaries, indicating that these genes may play important roles in regulation of
      egg production. Among these 843 DEGs, 685 were assigned to gene ontology (GO)
      categories. Of these, 25 genes were related to reproduction, and 30 were related
      to the reproductive process, including some associated with ovarian follicle
      development, circadian regulation of gene expression, circadian rhythm, and
      estrogen receptor binding. Furthermore, some important functional pathways were
      revealed, such as the steroid biosynthesis pathway, the endocrine and other
      factor-regulated calcium reabsorption pathways, circadian rhythm, the neuroactive
      ligand-receptor interaction pathway, fatty acid biosynthesis, and the calcium
      signaling pathway, which appear to be much more active in the HEP group, as
      compared to those of the LEP group. The results of this study provide very useful
      information that may contribute to future functional studies of genes involved in
      bird reproduction.

PMID- 29053814
TI  - Effects of canola meal source on the standardized ileal digestible amino acids
      and apparent metabolizable energy contents for broiler chickens.
AB  - Two studies were conducted to determine the effect of canola meal source on the
      standardized ileal digestible amino acids (AA) and nitrogen-corrected apparent
      metabolizable energy (AMEn) contents of canola meal (CM) from 6 processing plants
      in Canada. Two plants provided CM in both mash and pellet forms, while the other
      4 provided CM in mash form only, giving a total of 8 samples. In the standardized
      ileal digestibility (SID) assay, 280 birds were housed 7 per cage and fed a
      commercial starter diet from 1 to 14 d of age followed by the test diets from 15
      to 21 d. Diets were formulated to contain CM as the only source of protein.
      Chromic oxide was included in all diets as an indigestible marker. Diets were
      randomly assigned to 5 cages of 7 birds. On d 21, birds were euthanized by CO2
      asphyxiation and digesta samples were collected from the terminal ileum for SID
      of AA. The SID values were calculated using ileal endogenous AA losses
      determination. In the AMEn assay, 330 birds were housed 6 per cage and fed a
      commercial starter diet from 1 to 14 d of age followed by the experimental diets
      from 15 to 19 d. The 8 experimental diets contained 30% of CM and 70% of a corn
      soybean meal-based diet. There were differences (P < 0.05) among CM samples in
      the standardized ileal digestible content of all AA. Standardized ileal
      digestible contents of Arg, Lys, Met, and Thr averaged 2.17, 1.74, 0.53, and
      1.03%, respectively. Pelleting reduced (P < 0.05) the standardized ileal
      digestible content of all AA in CM from one of the plants. There were differences
      (P<0.05) among CM samples in the AMEn contents with values ranging from 1,590 to
      2,041 kcal/kg DM. In conclusion, there was effect of CM source on the
      standardized ileal digestible AA and AMEn contents. Regression equations for
      predicting standardized ileal digestible contents of selected AA from a simple
      measure of acid detergent fiber (ADF) were developed.

PMID- 29053815
TI  - Insulin immuno-neutralization decreases food intake in chickens without altering
      hypothalamic transcripts involved in food intake and metabolism.
AB  - In mammals, insulin regulates blood glucose levels and plays a key regulatory
      role in appetite via the hypothalamus. In contrast, chickens are characterized by
      atypical glucose homeostasis, with relatively high blood glucose levels, reduced
      glucose sensitivity of pancreatic beta cells, and large resistance to exogenous
      insulin. The aim of the present study was to investigate in chickens the effects
      of 5 h fasting and 5 h insulin immuno-neutralization on hypothalamic mRNA levels
      of 23 genes associated with food intake, energy balance, and glucose metabolism.
      We observed that insulin immune-neutralization by administration of anti-porcine
      insulin guinea pig serum (AI) significantly decreased food intake and increased
      plasma glucose levels in chickens, while 5 h fasting produced a limited and non
      significant reduction in plasma glucose. In addition, 5 h fasting increased
      levels of NPY, TAS1R1, DIO2, LEPR, GLUT1, GLUT3, GLUT8, and GCK mRNA. In
      contrast, AI had no impact on the levels of any selected mRNA. Therefore, our
      results demonstrate that in chickens, food intake inhibition or satiety
      mechanisms induced by insulin immuno-neutralization do not rely on hypothalamic
      abundance of the 23 transcripts analyzed. The hypothalamic transcripts that were
      increased in the fasted group are likely components of a mechanism of adaptation
      to fasting in chickens.

PMID- 29053816
TI  - Histomorphometric study of the anterior latissimus dorsi muscle and evaluation of
      enzymatic markers of broilers affected with dorsal cranial myopathy.
AB  - Dorsal cranial myopathy (DCM), which affects the anterior latissimus dorsi (ALD)
      muscles of commercial broilers, is of unknown etiology, and it represents up to
      6% of the partial condemnations in Brazilian slaughterhouses. This study was
      performed to achieve histomorphometric characterizations of the ALD muscles from
      male Cobb 500 broilers slaughtered at either 35 d or 42 d and to evaluate the
      effects of DCM on the enzymatic markers aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), creatine kinase (CK), and lactate dehydrogenase (LDH) and
      on uric acid and creatinine metabolites. Blood samples (1.5 to 3 mL) and ALD
      muscle fragments were collected from each carcass, all of which were processed in
      a commercial inline processing system. For each age, twelve macroscopically
      normal animals and twelve animals found to exhibit DCM were randomly selected for
      histomorphometric evaluation and analysis of serologic profiles. Microscopic
      evaluations demonstrated that the muscle fibers of those with DCM exhibited a
      strong presence of multifocal regenerative myodegeneration as well as a
      substitution of muscle tissue with connective tissue (P < 0.001) through
      fibrosis, thus characterizing the chronicity and hardness of the affected muscle.
      It is suggested that DCM is a localized muscle lesion because the detected serum
      levels of CK (P < 0.001), AST (P < 0.001), ALT (P = 0.01), and LDH (P < 0.001)
      enzymes were strongly associated with the group affected by DCM. Additional
      studies are needed to gain an understanding of this myopathy because it is an
      emerging problem in the poultry industry. In addition, it is related to DCM
      lesions in fast-growing broilers with the greatest slaughter weights.

PMID- 29053818
TI  - Effect of dietary supplementation of nitrocompounds on Salmonella colonization
      and ileal immune gene expression in laying hens challenged with Salmonella
      Enteritidis.
AB  - Foodborne disease caused by Salmonella Enteritidis (SE) is one of the important
      public health and economic concerns. A study was conducted to determine the
      effect of supplementation with 2-nitroethanol (NE) and 2-nitropropanol (NP) on
      Salmonella recovery of internal organs as well as on the immune gene expression
      in the ileum of laying hens. Thirty-six White Leghorns were orally gavaged with
      nalidixic acid resistant Salmonella Enteritidis (SENR). Hens were housed
      individually in wire-laying cages and randomly assigned to six dietary
      treatments: T1 = SENR unchallenged (negative control), T2 = SENR challenged
      (positive control), T3 = SENR challenged + 100 ppm NE, T4 = SENR challenged + 200
      ppm NE, T5 = SENR challenged + 100 ppm NP, and T6 = SENR challenged + 200 ppm NP.
      Hens were sampled at 7 days post inoculation (dpi). Ceca, liver with gall bladder
      (L/GB), and ovary samples were collected for bacteriology, and ileum samples were
      collected for analysis of immune gene expression. T3 and T6 significantly reduced
      (P < 0.05) cecal SENR count, whereas T4 and T5 were not different from T2, the
      SENR challenged control. There was no significant difference in SENR reduction in
      the L/GB or ovary after supplementation of either nitrocompounds. Pro- and anti
      inflammatory cytokines such as interferon (IFN)-gamma, interleukin (IL)-1B, IL-6,
      toll-like receptors (TLR)-4, and IL-10 all were significantly upregulated (P <
      0.05) after SENR challenge. Supplementation at both levels of NE and NP showed a
      significant immune gene expression response in the ileum with reduction of IFN
      gamma, IL-6, TLR-4, and IL-10 mRNA expression. Overall, nitrocompounds such as NE
      and NP can be used in the intervention strategy to reduce Salmonella infection in
      hens.

PMID- 29053817
TI  - Autophagic flux is required for the synthesis of triacylglycerols and ribosomal
      protein turnover in Chlamydomonas.
AB  - Autophagy is an intracellular catabolic process that allows cells to recycle
      unneeded or damaged material to maintain cellular homeostasis. This highly
      dynamic process is characterized by the formation of double-membrane vesicles
      called autophagosomes, which engulf and deliver the cargo to the vacuole. Flow of
      material through the autophagy pathway and its degradation in the vacuole is
      known as autophagic flux, and reflects the autophagic degradation activity. A
      number of assays have been developed to determine autophagic flux in yeasts,
      mammals, and plants, but it has not been examined yet in algae. Here we analyzed
      autophagic flux in the model green alga Chlamydomonas reinhardtii. By monitoring
      specific autophagy markers such as ATG8 lipidation and using immunofluorescence
      and electron microscopy techniques, we show that concanamycin A, a vacuolar
      ATPase inhibitor, blocks autophagic flux in Chlamydomonas. Our results revealed
      that vacuolar lytic function is needed for the synthesis of triacylglycerols and
      the formation of lipid bodies in nitrogen- or phosphate-starved cells. Moreover,
      we found that concanamycin A treatment prevented the degradation of ribosomal
      proteins RPS6 and RPL37 under nitrogen or phosphate deprivation. These results
      indicate that autophagy might play an important role in the regulation of lipid
      metabolism and the recycling of ribosomal proteins under nutrient limitation in
      Chlamydomonas.

PMID- 29053819
TI  - Changes in immune and metabolic gut response in broilers fed beta-mannanase in
      beta-mannan-containing diets.
AB  - beta-galactomannans found in soy-based broiler feed are known to cause
      physiological effects that are hypothesized to be related to gut inflammation.
      Previous studies have shown that the incorporation of beta-mannanase in the diet
      or as a supplement results in improvements to certain performance parameters
      related to gut health and feed conversion. Using kinome analysis, we
      characterized the mechanism of beta-galactomannan activity and supplementation
      with beta-mannanase on the gut of commercial broilers to understand the mode of
      action. Two doses of beta-mannanase (200 and 400 g/ton of feed) with and without
      inclusion of additional beta-galactomannan (3,000 ppm) were tested at 3 time
      points (d 14, d 28, and d 42 post hatch). Broilers were fed starter (d 0 to 14),
      grower (d 15 to 28), and finisher diets (d 29 to 42). Jejuna were collected from
      birds from each treatment condition and time point. Cluster analysis of the
      kinome data showed that birds clustered first by age, then predominantly by
      whether beta-mannanase had been included in the diet. Biological pathway analysis
      showed that the inclusion of additional beta-galactomannan into the diet resulted
      in increased signaling related to immune response, relative to our normal control
      diet (with reduced soybean meal). The addition of beta-mannanase to the enhanced
      beta-galactomannan diet eliminated the majority of this immune-related signaling,
      indicating that the feed-induced immune response within the jejuna had been
      eliminated by the addition of beta-mannanase. We also saw changes in specific
      metabolic and gut function pathways in birds fed beta-mannanase. These observed
      changes in beta-mannanase-fed birds are likely the mechanism for the enhanced
      performance and feed conversion observed in birds given beta-mannanase in their
      diets.

PMID- 29053820
TI  - Mood Disorders and Risk of Herpes Zoster in 2 Population-Based Case-Control
      Studies in Denmark and the United Kingdom.
AB  - We examined the association between mood disorders and risk of herpes zoster in
      two case-control studies using data from nationwide Danish registries and
      practices in the UK Clinical Practice Research Datalink. We included incident
      zoster cases diagnosed in general practice (using systemic antivirals as a proxy
      in Denmark) or hospital during 1997-2013 in Denmark (n = 190,671) and during 2000
      2013 in the United Kingdom (n = 177,361). We risk-set sampled 4 matched
      population controls per case. Conditional logistic regression analyses adjusting
      for zoster risk factors showed that the odds ratios for previous mood disorder
      among cases versus controls were 1.15 (99% confidence interval (CI): 1.12, 1.19;
      prevalence 7.1% vs. 6.0%) in Denmark and 1.12 (99% CI: 1.11, 1.14; prevalence
      31.6% vs. 29.2%) in the United Kingdom. In Denmark, odds ratios were higher for
      anxiety (1.23; 99% CI: 1.17, 1.30) and severe stress and adjustment disorder
      (1.24; 99% CI: 1.18, 1.30) than for depression (1.11; 99% CI: 1.07, 1.14). In the
      United Kingdom, odds ratios for these conditions were similar: 1.12 (99% CI:
      1.10, 1.13), 1.12 (99% CI: 1.10, 1.14), and 1.14 (99% CI: 1.10, 1.19) for
      depression, anxiety, and severe stress and adjustment disorder, respectively. In
      conclusion, mood disorders were associated with an increased risk of zoster.

PMID- 29053821
TI  - A null mutation in MICU2 causes abnormal mitochondrial calcium homeostasis and a
      severe neurodevelopmental disorder.
AB  - Mitochondrial calcium homeostasis is a tightly controlled process that is
      required for a variety of cellular functions. The mitochondrial calcium uniporter
      complex plays a critical role in this process. MICU2 is a major component of the
      mitochondrial calcium uniporter complex and its deficiency has been shown to
      impair mitochondrial calcium [Ca2+]m homeostasis although the exact mechanism
      remains unclear. We used exome sequencing, positional mapping, and functional
      characterization of MICU2 deficiency to investigate the role of MICU2 in calcium
      homeostasis. Using combined autozygome/exome analysis, a homozygous truncating
      mutation in MICU2 was found to fully segregate with a neurodevelopmental disorder
      in the form of severe cognitive impairment, spasticity, and white matter
      involvement in a multiplex consanguineous family. Patient-derived MICU2-deficient
      cells displayed impaired [Ca2+]m homeostasis, with associated increase in
      mitochondrial sensitivity to oxidative stress, and abnormal regulation of inner
      mitochondrial membrane potential. This is the first demonstration of MICU2
      deficiency in humans, which we suggest causes a distinct neurodevelopmental
      phenotype secondary to impaired mitochondrial calcium uniporter-mediated
      regulation of intracellular calcium homeostasis.

PMID- 29053822
TI  - Characterization of indigenous chicken production systems in Rwanda.
AB  - Characterization of indigenous chicken (IC) production systems in Rwanda was
      conducted from November 2015 to January 2016 with the aim of understanding socio
      economic characteristics, management of IC, production parameters, feed
      resources, and constraints faced by farmers rearing IC. A survey involving 206
      households was carried out in 5 districts with the highest populations of IC
      using structured questionnaires. Data were analyzed using SAS software. The
      results showed that the majority of respondents (62.4%) were males and 37.6% were
      females. The majority of respondents (83.6%) had formal education. All family
      members were involved in the chicken husbandry practices. However, women (78%)
      were highly responsible for IC management activities. The family size averaged 5
      persons (ranging 2 to 13) per household. Land was privately owned by farmers
      (84%) with a mean holding of 0.87 ha per household. The production system was
      mainly extensive with minimum provision of supplementary feeds. Chickens were
      being housed in separate houses at night and mating was uncontrolled. Breeding
      and replacement stocks were mainly sourced from the hatching of eggs using broody
      hens (60.68% of respondents). There were no vaccination programs, and ecto- and
      endo-parasites control was done when need arose. Egg production, income
      generation, meat production, and production of breeding stock were the main
      reasons of keeping IC. The first 3 main challenges facing IC production were
      diseases outbreaks, lack of investment capital, and predators. Others challenges,
      such as feed shortage, thieves, fluctuation of market price, lack of information
      on poultry rearing, and lack of chicken houses, also were mentioned. The IC
      production constraints mentioned need urgent mitigation measures to sustain
      utilization of IC against the changing climatic and economic conditions.
      Therefore, individual, public institution, and non-governmental organization
      efforts are required to develop sustainable breeding objectives directed to
      functions of IC and production challenges faced in the systems.

PMID- 29053823
TI  - Effect of maternally derived antibody on sequential infection with highly
      virulent bursal disease virus in newly hatched broilers.
AB  - Maternally derived antibodies (MDAs) are important for protection against very
      virulent infectious bursal disease virus (vvIBDV). In this study, 5-day-old
      commercial broilers with non-uniform MDA titers (with a coefficient of variation
      of 50%) were challenged with vvIBDV and given free contact with each other during
      a 2-week period. The chicks were assigned to four MDA-titer subgroups, GI-1 (very
      low MDA), GI-2 (low MDA), GI-3 (medium MDA), and GI-4 (high MDA). Transient
      symptoms of infection were observed in 35.7% of challenged birds. Body weight
      gain was significantly lower in GI-2, GI-3, and GI-4 birds than in an
      unchallenged control group. Seroconversion was observed in GI-1 birds and some GI
      2 birds. The frequency of virus shedding via the cloaca in vvIBDV-challenged
      birds increased from 7.1% of GI birds at 5 days post inoculation (dpi) to 35.7%
      at 14 dpi. The timing of virus shedding was progressively later from GI-1 to GI
      4. At 14 dpi, significant atrophy of the bursa of Fabricius (BF) was observed in
      GI birds compared with GII controls; atrophy was most severe in GI-1 birds and
      least severe in GI-4 birds. BF lesion scores decreased from GI-1 to GI-4. The
      proportion of birds with IBDV antigen in the BF at 14 dpi was higher in GI-2 and
      GI-3 than in GI-1 and GI-4, whereas the viral load in positive birds increased
      from GI-1 to GI-4. Our results indicate that high levels of MDAs would protect
      chicks from initial vvIBDV infection but that progressive decay of these MDAs
      would result in delayed infection by virus shedding in initially infected birds
      with low MDA titers, resulting in continuous circulation of the virus in a flock
      with non-uniform MDA titers.

PMID- 29053824
TI  - Chemogenetic locus coeruleus activation restores reversal learning in a rat model
      of Alzheimer's disease.
AB  - See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary
      on this article.Clinical evidence suggests that aberrant tau accumulation in the
      locus coeruleus and noradrenergic dysfunction may be a critical early step in
      Alzheimer's disease progression. Yet, an accurate preclinical model of these
      phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss
      of locus coeruleus innervation and deficits locus coeruleus/norepinephrine
      modulated behaviours, does not exist, hampering the identification of underlying
      mechanisms and the development of locus coeruleus-based therapies. Here, a
      transgenic rat (TgF344-AD) expressing disease-causing mutant amyloid precursor
      protein (APPsw) and presenilin-1 (PS1DeltaE9) was characterized for histological
      and behavioural signs of locus coeruleus dysfunction reminiscent of mild
      cognitive impairment/early Alzheimer's disease. In TgF344-AD rats,
      hyperphosphorylated tau was detected in the locus coeruleus prior to accrual in
      the medial entorhinal cortex or hippocampus, and tau pathology in the locus
      coeruleus was negatively correlated with noradrenergic innervation in the medial
      entorhinal cortex. Likewise, TgF344-AD rats displayed progressive loss of
      hippocampal norepinephrine levels and locus coeruleus fibres in the medial
      entorhinal cortex and dentate gyrus, with no frank noradrenergic cell body loss.
      Cultured mouse locus coeruleus neurons expressing hyperphosphorylation-prone
      mutant human tau had shorter neurites than control neurons, but similar cell
      viability, suggesting a causal link between pretangle tau accrual and altered
      locus coeruleus fibre morphology. TgF344-AD rats had impaired reversal learning
      in the Morris water maze compared to their wild-type littermates, which was
      rescued by chemogenetic locus coeruleus activation via designer receptors
      exclusively activated by designer drugs (DREADDs). Our results indicate that
      TgF344-AD rats uniquely meet several key criteria for a suitable model of locus
      coeruleus pathology and dysfunction early in Alzheimer's disease progression, and
      suggest that a substantial window of opportunity for locus coeruleus/
      norepinephrine-based therapeutics exists.

PMID- 29053825
TI  - PDM3, a pentatricopeptide repeat-containing protein, affects chloroplast
      development.
AB  - The chloroplast, as the photosynthetic organelle of plants, plays a crucial role
      in plant development. Extensive studies have been conducted on chloroplast
      development; however, the related regulatory mechanism still remains elusive.
      Here, we characterized a mutant with defective chloroplasts in Arabidopsis,
      termed pigment-defective mutant3 (pdm3), which exhibits a distinct albino
      phenotype in leaves, eventually leading to pdm3 seedling lethality under
      autotrophic growth conditions. Electron microscopy demonstrated that the number
      of thylakoids was reduced and the structure of those thylakoids was disrupted in
      the pdm3 mutant, which eventually led to the breakdown of chloroplasts. Sequence
      analysis showed that PDM3 encodes a chloroplast protein consisting of 12
      pentratricopeptide repeat domains that belongs to the P subgroup. Both confocal
      microscopic analysis and immunoblotting in the chloroplast protein fraction
      showed that PDM3 was located in the stroma. Furthermore, analysis of the
      transcript profiles of chloroplast genes revealed that plastid-encoded polymerase
      dependent transcript levels were markedly reduced, while nuclear-encoded
      polymerase-dependent transcript levels were increased in pdm3 mutants. In
      addition, we found that the splicing of introns in trnA, ndhB, and clpP-1 is also
      affected in pdm3. Taken together, we propose that PDM3 plays an essential role in
      chloroplast development in Arabidopsis.

PMID- 29053826
TI  - Induction of somatic mutations by low-dose X-rays: the challenge in recognizing
      radiation-induced events.
AB  - It is difficult to distinguish radiation-induced events from spontaneous events
      during induction of stochastic effects, especially in the case of low-dose or low
      dose-rate exposures. By using a hypersensitive system for detecting somatic
      mutations at the HPRT1 locus, we investigated the frequency and spectrum of
      mutations induced by low-dose X-rays. The mutant frequencies induced by doses of
      >0.15 Gy were statistically significant when compared with the spontaneous
      frequency, and a clear dose dependency was also observed for mutant frequencies
      at doses of >0.15 Gy. In contrast, mutant frequencies at doses of <0.1 Gy
      occurred at non-significant levels. The mutation spectrum in HPRT-deficient
      mutants revealed that the type of mutations induced by low-dose exposures was
      similar to that seen in spontaneous mutants. An apparent change in mutation type
      was observed for mutants induced by doses of >0.2 Gy. Our observations suggest
      that there could be a critical dose for mutation induction at between 0.1 Gy and
      0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks
      (DSBs). These observations also suggest that low-dose radiation delivered at
      doses of <0.1 Gy may not result in DSB-induced mutations but may enhance
      spontaneous mutagenesis events.

PMID- 29053827
TI  - Comparative evaluation of texture wheat ingredients and soy proteins in the
      quality and acceptability of emulsified chicken nuggets.
AB  - Chicken nuggets are commonly made with varying levels of textured vegetable
      proteins, such as soy and wheat, for their ability to bind water and their meat
      like conformation. This project compared textured wheat proteins and soy proteins
      at 10%, 20%, 30%, and 40% in emulsified chicken nuggets. A total of 3,024 chicken
      nuggets were evaluated in replications for batter breader pickup (%), par fry
      yield (%), cook loss (%), L*, a*, b* color value, texture profile analysis, and
      sensory analysis. The analysis was conducted for all 4 concentrations of wheat
      and soy treatments then compared to each other and an all white meat chicken
      nugget control. All data were analyzed with an alpha < 0.05 using SAS with PROC
      GLM and Duncan's MRT, except for sensory data, which were analyzed as a complete
      randomized block design using analysis of variance with a alpha < 0.05 and was
      analyzed using SAS with PROC GLM. Chicken nuggets prepared with increasing levels
      of textured soy and wheat proteins exhibited generally similar properties in
      terms of yields, color, and objective texture. Trained panel sensory analysis
      indicated an increased detection of soy flavors over wheat flavors at higher
      inclusion percentages (30% and 40%); however, these results do not have any
      implication of consumer acceptance.

PMID- 29053828
TI  - Effect of synbiotic supplementation on layer production and cecal Salmonella load
      during a Salmonella challenge.
AB  - This study analyzed the inhibitory effects of a synbiotic product (PoultryStar(r)
      me) on production parameters, intestinal microflora profile, and immune
      parameters in laying hens with and without a Salmonella challenge. The synbiotic
      product contained 4 probiotic bacterial strains (Lactobacillus reuteri,
      Enterococcus faecium, Bifidobacterium animalis, and Pediococcus acidilactici) and
      a prebiotic fructooligosaccharide. Layers were supplemented with the synbiotic
      from d of hatch to 28 wk of age. At 16 wk of age, birds were either vaccinated
      with Salmonella enterica Enteritidis (SE) vaccine or left unvaccinated. At 24 wk
      of age, a portion of the birds was challenged with 1 * 109 CFU of SE or left
      unchallenged, resulting in a 3 (vaccinated, challenged, or both vaccinated and
      challenged) X 2 (control and synbiotics) factorial arrangement of treatments. At
      18 and 20 wk of age, birds fed synbiotics in both vaccinated and unvaccinated
      groups had increased (P < 0.05) BW more than those in the un-supplemented groups.
      Birds fed synbiotics had 0.7, 17.8, 21.7, 3, and 4.2% higher (P < 0.05) hen d egg
      production (HDEP) at 19, 20, 21, 22, and 23 wk of age, compared to the birds
      without supplementation, respectively. After administering the SE challenge,
      supplemented birds had 3, 6.7, 4.3, 12.5, and 14.4% higher (P < 0.05) HDEP at 24,
      25, 26, 27, and 28 wk of age, compared to the birds not supplemented,
      respectively. Irrespective of the vaccination status, birds fed synbiotics and
      challenged with SE had a lower (P < 0.05) SE cecal load compared to the un
      supplemented groups. At 22 d post Salmonella challenge, birds supplemented,
      vaccinated, and challenged had the highest bile IgA content. It can be concluded
      that supplementation of the synbiotic product could be beneficial to layer diets
      as a growth promoter, performance enhancer, and for protection against SE
      infection.

PMID- 29053829
TI  - Letter: Clinical Outcomes Following Surgical Management of Coexisting Parkinson
      Disease and Cervical Spondylotic Myelopathy.

PMID- 29053831
TI  - Effect of dietary fiber levels on performance, gizzard development, intestinal
      morphology, and nutrient utilization in meat ducks from 1 to 21 days of age.
AB  - The objective of this experiment was to determine the effects of dietary fiber
      levels on growth performance, gizzard development, intestinal morphology, and
      nutrient utilization in Cherry Valley meat ducks. In total, 720 1-day-old
      ducklings were fed with starter diets (120 ducklings, 8 pens of 15 ducklings, on
      each diet) containing 6 levels of crude fiber (CF, 1.46, 3.09, 4.15, 6.18, 7.52,
      and 9.03%, based on analysis) for 21 d. Then, on d 22, ducks fed all of the
      starter diets were transferred to a grower diet (containing 4% CF) to examine the
      residual effect of starter dietary fiber levels until 35 d. Body weight (BW),
      body weight gain (BWG), feed intake (FI), feed to gain ratio (F:G) were
      recorded/calculated weekly. Ducks were sampled for gizzard development and
      intestinal morphology determination on d 7, 14, and 21. Nutrient utilization was
      assessed using 25- to 27-day-old ducks. The results showed that BW (d 21), BWG (d
      15 to 21, d 1 to 21), and F:G (d 15 to 21, d 1 to 21, and d 1 to 35) were
      increased quadratically (P < 0.01), and FI (all periods except for d 22 to 35)
      was increased linearly (P < 0.01), when starter dietary CF levels increased from
      1.46 to 9.03%. Ducks under 3.09% and 4.15% CF starter diets had decreased 1 to 35
      d FI and F:G when compared to ducks under other starter diets. When compared to
      ducks fed 1.46% and 3.09% CF starter diets, ducks fed starter diet containing
      7.52% CF had increased gizzard development, jejunal morphology, energy retention,
      excreta nutrients availability, and standardized ileal digestibility (SID) of
      Arg, Ile, Leu, Thr, Val, Asp, Ala, Glu, Gly, Pro, Ser, and total amino acids. In
      conclusion, meat ducks from 1 to 21 d of age could adapt to a wide range (3.09%
      to 7.52%) of dietary fiber levels.

PMID- 29053830
TI  - Friedreich's ataxia: clinical features, pathogenesis and management.
AB  - Introduction: Friedreich's ataxia is the most common inherited ataxia. Sources of
      data: Literature search using PubMed with keywords Friedreich's ataxia together
      with published papers known to the authors. Areas of agreement: The last decade
      has seen important advances in our understanding of the pathogenesis of disease.
      In particular, the genetic and epigenetic mechanisms underlying the disease now
      offer promising novel therapeutic targets. Areas of controversy: The search for
      effective disease-modifying agents continues. It remains to be determined whether
      the most effective approach to treatment lies with increasing frataxin protein
      levels or addressing the metabolic consequences of the disease, for example with
      antioxidants. Areas timely for developing research: Management of Freidreich's
      ataxia is currently focussed on symptomatic management, delivered by the
      multidisciplinary team. Phase II clinical trials in agents that address the
      abberrant silencing of the frataxin gene need to be translated into large placebo
      controlled Phase III trials to help establish their therapeutic potential.

PMID- 29053832
TI  - Reward deficits in behavioural variant frontotemporal dementia include
      insensitivity to negative stimuli.
AB  - During reward processing individuals weigh positive and negative features of a
      stimulus to determine whether they will pursue or avoid it. Though patients with
      behavioural variant frontotemporal dementia display changes in their pursuit of
      rewards, such as food, alcohol, money, and sex, the basis for these shifts is not
      clearly established. In particular, it is unknown whether patients' behaviour
      results from excessive focus on rewards, insensitivity to punishment, or to
      dysfunction in a particular stage of reward processing, such as anticipation,
      consumption, or action selection. Our goal was to determine the nature of the
      reward deficit in behavioural variant frontotemporal dementia and its underlying
      anatomy. We devised a series of tasks involving pleasant, unpleasant, and neutral
      olfactory stimuli, designed to separate distinct phases of reward processing. In
      a group of 25 patients with behavioural variant frontotemporal dementia and 21
      control subjects, diagnosis by valence interactions revealed that patients with
      behavioural variant frontotemporal dementia rated unpleasant odours as less
      aversive than did controls and displayed lower skin conductance responses when
      anticipating an upcoming aversive odour. Subjective pleasantness ratings and skin
      conductance responses did not differ between behavioural variant frontotemporal
      dementia and controls for pleasant or neutral smells. In a task designed to
      measure the effort subjects would expend to smell or avoid smelling a stimulus,
      patients with behavioural variant frontotemporal dementia were less motivated,
      and therefore less successful than control subjects, at avoiding what they
      preferred not to smell, but had equivalent success at obtaining stimuli they
      found rewarding. Voxel-based morphometry of patients with behavioural variant
      frontotemporal dementia revealed that the inability to subjectively differentiate
      the valence of pleasant and unpleasant odours correlated with atrophy in right
      ventral mid-insula and right amygdala. High pleasantness ratings of unpleasant
      stimuli correlated with left dorsal anterior insula and frontal pole atrophy.
      These findings indicate that insensitivity to negative information may be a key
      component of the reward-seeking behaviours in behavioural variant frontotemporal
      dementia, and may relate to degeneration of structures that are involved in
      representing the emotional salience of sensory information.

PMID- 29053834
TI  - Effect of feed supplementation with zinc glycine chelate and zinc sulfate on
      cytokine and immunoglobulin gene expression profiles in chicken intestinal
      tissue.
AB  - The aim of the study was to evaluate the effect of inorganic and organic forms of
      Zn on the expression of cytokines (IL-2, TNF-alpha, IFN-gamma, IL-12, IL-17, IL
      4, IL-10, and TGF-beta) and immunoglobulins (IgA and IgG) in the tissues of the
      small intestine (jejunum and ileum) of broiler chickens. In the experiment, 90
      broiler chickens were divided into 4 experimental groups and a control group,
      with 18 birds each. The birds received Zn supplements in inorganic form with and
      without phytase (ZnSO4 and ZnSO4 + F), and in organic form with glycine, with and
      without phytase (Zn-Gly and Zn-Gly + F). The total rearing period was 42 days.
      Quantitative real-time (RT)-PCR was used to measure the expression of the
      cytokines and immunoglobulins. The differences between the results obtained for
      the control and experimental groups, between the groups receiving ZnSO4 and Zn
      Gly, and between groups ZnSO4-F and Zn-Gly-F were analyzed statistically. High
      relative expression of IL-2 was observed for the chickens in the groups receiving
      ZnSO4-F, Zn-Gly, and Zn-Gly-F on d 42 in comparison to the control group. High
      relative expression of TNF-alpha, IL-12, and IL-17 was noted in the group that
      received ZnSO4 + F. High expression of IgG, IgA, IL-4, TGF-beta, and IL-10 was
      noted in the groups of chickens that received feed supplemented with Zn-Gly and
      Zn-Gly + F chelates on d 42 of the study in comparison to the control group. In
      conclusion, supplementation with Zn-Gly chelates can ensure Th1 and Th2 balance
      during the immune response in the gut-associated lymphoid tissue (GALT), and, by
      increasing IgA and IgG expression, also can stimulate potentiation of the immune
      response involved in passive protection of the body from infection. In contrast,
      the use of inorganic forms of Zn, in the form of sulfates, can induce local
      inflammatory processes in the intestines, which, in the case of long-term
      supplementation, lead to the development of infections.

PMID- 29053833
TI  - Clinical, pathological and functional characterization of riboflavin-responsive
      neuropathy.
AB  - Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor,
      sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and
      respiratory problems leading to ventilator-dependence. Loss-of-function mutations
      in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been
      linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency,
      neuropathology and downstream consequences of riboflavin transporter mutations
      are unclear. By screening a large cohort of 132 patients with early-onset severe
      sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link
      between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome,
      identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were
      novel. Brain and spinal cord neuropathological examination of two cases with
      SLC52A3 mutations showed classical symmetrical brainstem lesions resembling
      pathology seen in mitochondrial disease, including severe neuronal loss in the
      lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of
      the spinothalamic and spinocerebellar tracts and posterior column-medial
      lemniscus pathways. Mitochondrial dysfunction has previously been implicated in
      an array of neurodegenerative disorders. Since riboflavin metabolites are
      critical components of the mitochondrial electron transport chain, we
      hypothesized that reduced riboflavin transport would result in impaired
      mitochondrial activity, and confirmed this using in vitro and in vivo models.
      Electron transport chain complex I and complex II activity were decreased in
      SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila
      melanogaster riboflavin transporter homologue revealed reduced levels of
      riboflavin, downstream metabolites, and electron transport chain complex I
      activity. This in turn led to abnormal mitochondrial membrane potential,
      respiratory chain activity and morphology. Riboflavin transporter knockdown in
      Drosophila also resulted in severely impaired locomotor activity and reduced
      lifespan, mirroring patient pathology, and these phenotypes could be partially
      rescued using a novel esterified derivative of riboflavin. Our findings expand
      the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere
      syndrome, implicate mitochondrial dysfunction as a downstream consequence of
      riboflavin transporter gene defects, and validate riboflavin esters as a
      potential therapeutic strategy.

PMID- 29053836
TI  - Long-term disability progression in primary progressive multiple sclerosis: a 15
      year study.
AB  - Prognostic markers of primary progressive multiple sclerosis evolution are
      needed. We investigated the added value of magnetic resonance imaging measures of
      brain and cervical cord damage in predicting long-term clinical worsening of
      primary progressive multiple sclerosis compared to simple clinical assessment. In
      54 patients, conventional and diffusion tensor brain scans and cervical cord T1
      weighted scans were acquired at baseline and after 15 months. Clinical evaluation
      was performed after 5 and 15 years in 49 patients. Lesion load, brain and cord
      atrophy, mean diffusivity and fractional anisotropy values from the brain normal
      appearing white matter and grey matter were obtained. Using linear regression
      models, we screened the clinical and imaging variables as independent predictors
      of 15-year disability change (measured on the expanded disability status scale).
      At 15 years, 90% of the patients had disability progression. Integrating clinical
      and imaging variables at 15 months predicted disability changes at 15 years
      better than clinical factors at 5 years (R2 = 61% versus R2 = 57%). The model
      predicted long-term disability change with a precision within one point in 38 of
      49 patients (77.6%). Integration of clinical and imaging measures allows
      identification of primary progressive multiple sclerosis patients at risk of long
      term disease progression 4 years earlier than when using clinical assessment
      alone.

PMID- 29053835
TI  - Abnormal intrinsic brain functional network dynamics in Parkinson's disease.

PMID- 29053837
TI  - PRELIMINARY STUDY OF NEUTRON FIELD IN TOP-IMPLART PROTON THERAPY BEAM.
AB  - The TOP-IMPLART, a new proton therapy facility, is under development in Frascati
      ENEA Laboratories, near Rome. The project is centered on a medium-energy proton
      accelerator designed as a sequence of modular linear accelerators (the final
      energy will be 230 MeV). Being not a commercial product, measurements and
      simulation are fundamental to characterize the system and the radiation field,
      even during its construction. In this work some preliminary evaluations of the
      neutron contamination have been tried. The simulations were validated through
      some measurements obtaining a satisfactory agreement. A more detailed
      calculations and measurements campaign is scheduled for the next future.

PMID- 29053838
TI  - MRI findings of visual system alterations in Parkinson's disease.

PMID- 29053839
TI  - Laying hens behave differently in artificially and naturally sourced ammoniated
      environments.
AB  - Laying hens are chronically exposed to high levels of ammonia (NH3), one of the
      most abundant aerial pollutants in poultry houses. Tests for aversion to NH3 in
      laying hens have used artificially sourced NH3/air mixtures (i.e., from a gas
      cylinder) showing that birds prefer fresh air to NH3. However, artificially
      sourced NH3/air mixtures may not accurately reflect barn air conditions, where
      manure emits a variety of gases. Herein, we investigated whether laying hens
      differentiate between artificially and naturally sourced NH3/air mixtures and how
      exposure to NH3 affects foraging and aversive behavior. A total of 20 laying hens
      was exposed to artificially sourced [A] (from an anhydrous NH3 cylinder) and
      naturally sourced [N] (from conspecific laying hen excreta) gas mixtures. Hens
      were exposed to A and N mixtures with NH3 concentrations of 25 and 45 ppm, as
      well as fresh air [FA]. During the experiment, all birds were exposed to each
      treatment 3 times using a custom-built polycarbonate chamber, containing a
      foraging area (containing raisins, mealworms, and feed mix) and a gas delivery
      system. All testing sessions were video recorded, analyzed with INTERACT(r)
      software, and subjected to a GLIMMIX procedure in SAS. Our results showed that
      the laying hens spent less time foraging overall (P < 0.001) and were slower to
      commence foraging (P = 0.004) in ammoniated environments compared to the fresh
      air. Laying hens were more likely to forage for a longer time (with fewer
      interruptions) in N than in A treatments (P < 0.001). Laying hens also reacted
      with greater aversion towards treatment A compared to treatment N (P < 0.001).
      These findings suggest that the laying hens of our study preferred fresh to
      ammoniated air and that they behaved differently in artificially and naturally
      sourced NH3/air mixtures, possibly due to the presence of familiar stimuli from
      the excreta. These findings have implications for new developments in
      methodological approaches for behavioral testing and for recommendations
      regarding NH3 levels inside poultry barns.

PMID- 29053840
TI  - EVALUATION OF NEUTRON SCATTERING CORRECTION USING THE SEMI-EMPIRICAL METHOD AND
      THE SHADOW-CONE METHOD FOR THE NEUTRON FIELD OF THE KOREA ATOMIC ENERGY RESEARCH
      INSTITUTE.
AB  - When neutron survey metres are calibrated in neutron fields, the results for room
      and air-scattered neutrons vary according to the distance from the source and
      the size, shape and construction of the neutron calibration room. ISO 8529-2
      recommends four approaches for correcting these effects: the shadow-cone method,
      semi-empirical method, generalised fit method and reduced-fitting method. In this
      study, neutron scattering effects are evaluated and compared using the shadow
      cone and semi-empirical methods for the neutron field of the Korea Atomic Energy
      Research Institute (KAERI). The neutron field is constructed using a 252Cf
      neutron source positioned in the centre of the neutron calibration room. To
      compare the neutron scattering effects using the two correction methods,
      measurements and simulations are performed using respectively KAERI's Bonner
      sphere spectrometer (BBS) and Monte Carlo N-Particle code at twenty different
      positions. Neutron spectra are measured by a europium-activated lithium iodide
      [6LiI(Eu)] scintillator in combination with the BBS. The calibration factors
      obtained using each methods show good agreement within 1.1%.

PMID- 29053841
TI  - Meat quality traits and proteome profile of woody broiler breast (pectoralis
      major) meat.
AB  - Woody breast meat has recently become prevalent in the broiler industry in both
      the United States and European Union. Recent publications have described the meat
      quality characteristics of woody breast meat as having hardened areas and pale
      ridge-like bulges at both the caudal and cranial regions of the breast. The
      present study investigated the meat quality (pH, color, cooking loss, and shear
      force) and protein quality characteristics (protein and salt-soluble protein
      content) in woody breast meat as compared to normal breast meat. In addition, the
      differences in the muscle proteome profiles of woody and normal breast meat were
      characterized. Results indicated that woody breast meat had a greater average pH
      (P < 0.0001) and cooking loss (P = 0.001) than normal breast meat, but woody
      breast meat did not differ in shear force (P > 0.05) in comparison to normal
      breast meat samples. The L*, a*, and b* values of woody breast fillets were
      greater than normal breast fillets (P < 0.0001 to L*; P = 0.002 to a*; P = 0.016
      to b*). The woody breast meat had more fat (P < 0.0001) and moisture (P < 0.021)
      and less protein (P < 0.0001) and salt-soluble protein (P < 0.0001) when compared
      with normal breast fillets. Whole muscle proteome analysis indicated 8 proteins
      that were differentially expressed (P < 0.05) between normal and woody breast
      meat samples. The differences in muscle proteome between normal and woody breast
      meat indicated an increased oxidative stress in woody breast meat when compared
      to normal meat. In addition, the abundance of some glycolytic enzymes, which are
      critical to the regeneration of adenosine triphosphate (ATP) in postmortem
      muscles, was lower in woody breast meat than in normal breast meat. Proteomic
      differences provide additional information on the biochemical pathways and
      genetic variations that lead to woody breast meat. Further research should be
      conducted to elucidate the genetic and nutritional contributions to the
      proliferation of woody breast meat in the United States.

PMID- 29053842
TI  - Differential expression of water channel- and noncoding RNA biogenesis-related
      genes in three lines of chickens under a short-term water restriction.
AB  - Genetic selection for high growth rate has resulted in tremendous changes not
      only in feed efficiency, but also in water consumption between modern broilers
      and their ancestor jungle fowl (JF). However molecular mechanisms involved in
      water homeostasis are still not well defined. This study aimed, therefore, to
      determine the effect of short-term water restriction on the expression of water
      channel- and noncoding RNA biogenesis-related genes in the kidney and whole blood
      of JF, broiler population from the 1990s (RB1995), and modern broiler population
      developed in 2015 (ARB2015). Body weight-matched birds from each population were
      subjected to water restriction (WR) for 3 h or had ad libitum access to water in
      a 3 * 2 factorial design. The expression of target genes was determined by real
      time quantitative PCR. WR significantly reduced body weight in RB1995, but not in
      JF or ARB2015. In the kidney, WR up-regulated the expression of AQP2 in all
      chicken populations, AQP3 in the RB1995, and ATP1B1 in JF and ARB2015. However,
      it down-regulated the expression of AQP4 in ARB2015 but had no effect on AVP
      expression. The expression of RNase III family enzymes also was altered by WR in
      a population-dependent manner, with DICER1 being down-regulated in JF and RB1995,
      Drosha was decreased in RB1995, and ARG2 was up-regulated in ARB2015. The
      expression of DGCR8 and TRBP1 was not affected by WR in any population; however,
      DGCR8 mRNA levels were significantly lower in RB1995 and ARB2015 compared to JF
      under both conditions. TRBP1 gene expression was significantly lower in RB1995
      and ARB2015 compared to JF under WR conditions. In the blood, the expression of
      these genes also was altered by WR, but with different patterns than the kidney.
      The mRNA abundances of AQP, AVP, DICER1, DGCR8, AGO2, and TRBP1 were
      significantly decreased by WR in RB1995. However, the expression of AQP2, AVP,
      DGCR8, and TRBP1 was increased in WR-ARB2015 compared to the control. In the JF,
      there was no difference in the expression of these genes except for a significant
      up-regulation of TRBP1 in WR compared to the control group. To the best of our
      knowledge, this is the first report showing that water channels and the RNase III
      enzymes are differentially regulated by WR in a population-dependent manner,
      which may be due to differential postnatal growth and maturation. Their
      expression in the circulation could open new vistas for identification of new
      molecular signatures involved in adaptation to water-deprivation stress.

PMID- 29053843
TI  - Effects of season and distance during transport on broiler chicken meat.
AB  - This research aims to evaluate the microclimate of commercial loads of broiler
      chickens at different distances in the summer (rainy) and winter (dry) seasons
      and their effects on meat quality. Twelve broiler loads were monitored with a
      total of 24 crates per load. Data loggers were used to record temperature and
      relative humidity. The experiment followed a completely randomized design with 48
      treatments in a factorial scheme (2 seasons: rainy and dry) x 2 (distances: short
      and long) x 12 (positions), with 3 replicates per experimental group. In the
      rainy season, meat quality was influenced by transport distance. For longer
      distances, it recorded the highest enthalpy comfort index (ECI), suggesting a
      tendency of dark, firm, and dry meat (DFD-like) and lower cooking losses (CL).
      The lowest ECI was recorded during the transport in dry season. Broiler chickens
      transported and slaughtered in the winter presented meat pH and L* (lightness)
      classified as "normal," but with higher cooking losses. For the shear force (SF),
      the seasons and distances had no significant influence on tenderness of the meat.
      Regarding the crate positioning in the load, no effect was observed during
      transport on this variable, given the meat quality characteristics of pH, L*, CL,
      and SF. These results suggest that the distance and the seasons present more
      influence on broiler meat quality than crate position in the truck.

PMID- 29053844
TI  - Evolutionally Conserved Function of Kisspeptin Neuronal System Is Nonreproductive
      Regulation as Revealed by Nonmammalian Study.
AB  - The kisspeptin neuronal system, which consists of a neuropeptide kisspeptin and
      its receptor Gpr54, is considered in mammals a key factor of reproductive
      regulation, the so-called hypothalamic-pituitary-gonadal (HPG) axis. However, in
      nonmammalian vertebrates, especially in teleosts, existence of kisspeptin
      regulation on the HPG axis is still controversial. In this study, we applied
      multidisciplinary techniques to a teleost fish, medaka, and examined possible
      kisspeptin regulation on the HPG axis. First, we generated knockout medaka for
      kisspeptin-related genes and found that they show normal fertility, gonadal
      maturation, and expression of gonadotropins. Moreover, the firing activity of
      GnRH1 neurons recorded by the patch clamp technique was not altered by kisspeptin
      application. Furthermore, in goldfish, in vivo kisspeptin administration did not
      show any positive effect on HPG axis regulation. However, as kisspeptin genes are
      completely conserved among vertebrates except birds, we surmised that kisspeptin
      should have some important nonreproductive functions in vertebrates. Therefore,
      to discover novel functions of kisspeptin, we generated a gpr54-1:enhanced green
      fluorescent protein (EGFP) transgenic medaka, whose gpr54-1-expressing cells are
      specifically labeled by EGFP. Analysis of neuronal projection of gpr54-1:EGFP
      expressing neurons showed that these neurons in the ventrolateral preoptic area
      project to the pituitary and are probably involved in endocrine regulation other
      than gonadotropin release. Furthermore, combination of deep sequencing,
      histological, and electrophysiological analyses revealed various novel neural
      systems that are under control of kisspeptin neurons-that is, those expressing
      neuropeptide Yb, cholecystokinin, isotocin, vasotocin, and neuropeptide B. Thus,
      our new strategy to genetically label receptor-expressing neurons gives insights
      into various kisspeptin-dependent neuronal systems that may be conserved in
      vertebrates.

PMID- 29053846
TI  - Corrigendum.

PMID- 29053845
TI  - Substitution of Yor1p NBD1 residues improves the thermal stability of Human
      Cystic Fibrosis Transmembrane Conductance Regulator.
AB  - The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a plasma
      membrane chloride channel protein that regulates vertebrate fluid homeostasis.
      The inefficiency of wild type human CFTR protein folding/trafficking is
      exacerbated by genetic mutations that can cause protein misfolding in the
      endoplasmic reticulum (ER) and subsequent degradation. This project investigates
      small changes in protein sequence that can alter the thermal stability of the
      large multi-domain CFTR protein. We target a conserved 70-residue alpha-subdomain
      located in the first nucleotide-binding domain that hosts the common misfolding
      mutation ?F508. To investigate substitutions that can stabilize this domain, we
      constructed chimeras between human CFTR and its closest yeast homolog Yor1p. The
      alpha-subdomain of Yor1p was replaced with that of CFTR in Saccharomyces
      cerevisiae. Cellular localization of green fluorescence protein-tagged Yor1p-CFTR
      chimeras was analyzed by fluorescence microscopy and quantitative multispectral
      imaging flow cytometry, steady-state protein levels were compared by SDS-PAGE and
      protein function probed by a phenotypic oligomycin resistance assay. The chimeras
      exhibited ER retention in yeast characteristic of defective protein
      folding/processing. Substitution of seven CFTR alpha-subdomain residues that are
      highly conserved in Yor1p and other transporters but differ in CFTR
      (S495P/R516K/F533L/A534P/K536G/I539T/R553K) improved Yor1p-CFTR chimera
      localization to the yeast plasma membrane. When introduced into human CFTR
      expressed in mammalian cells, the same substitutions improve the purified protein
      thermal stability. This stabilized human CFTR protein will be directly useful for
      structural and biophysical studies that have been limited by the thermal
      sensitivity of wild type CFTR. The insights into critical structural residues
      within CFTR could facilitate development of effective therapeutics for CF-causing
      mutations.

PMID- 29053848
TI  - Is Virtual Reality Ready for Prime Time in the Medical Space? A Randomized
      Control Trial of Pediatric Virtual Reality for Acute Procedural Pain Management.
AB  - Objective: To conduct a randomized control trial to evaluate the feasibility and
      efficacy of virtual reality (VR) compared with standard of care (SOC) for
      reducing pain, anxiety, and improving satisfaction associated with blood draw in
      children ages 10-21 years. Methods: In total, 143 triads (patients, their
      caregiver, and the phlebotomist) were recruited in outpatient phlebotomy at a
      pediatric hospital and randomized to receive either VR or SOC when undergoing
      routine blood draw. Patients and caregivers completed preprocedural and
      postprocedural standardized measures of pain, anxiety, and satisfaction, and
      phlebotomists reported about the patient's experience during the procedure.
      Results: Findings showed that VR significantly reduced acute procedural pain and
      anxiety compared with SOC. A significant interaction between patient-reported
      anxiety sensitivity and treatment condition indicated that patients undergoing
      routine blood draw benefit more from VR intervention when they are more fearful
      of physiological sensations related to anxiety. Patients and caregivers in the VR
      condition reported high levels of satisfaction with the procedure. Conclusion: VR
      is feasible, tolerated, and well-liked by patients, caregivers, and phlebotomists
      alike for routine blood draw. Given the immersive and engaging nature of the VR
      experience, VR has the capacity to act as a preventive intervention transforming
      the blood draw experience into a less distressing, potentially pain-free routine
      medical procedure, particularly for pediatric patients with high anxiety
      sensitivity. VR holds promise to reduce negative health outcomes for children and
      reduce distress in caregivers, while facilitating increased satisfaction and
      throughput in hectic outpatient phlebotomy clinics.

PMID- 29053847
TI  - Effect of low incubation temperature and low ambient temperature until 21 days of
      age on performance and body temperature in fast-growing chickens.
AB  - Thermal manipulation during embryogenesis was previously reported to decrease the
      occurrence of ascites and to potentially improve cold tolerance of broilers. The
      objective of our study was to explore the effects of the interaction of cold
      incubation temperatures and cool ambient temperatures until 21 d of age on
      performance and body temperature. Ross 308 eggs were incubated either under
      control conditions I0 (37.6 degrees C) or with cyclic cold stimulations I1 (6 h/d
      at 36.6 degrees C from d 10 to 18 of incubation) or with 2 cold stimulations I2
      (30 min at 15 degrees C) at d 18 and 19 of incubation. These treatments were
      followed by individual rearing and postnatal exposure to either standard rearing
      temperature T0 (from 33 degrees C at hatching to 21 degrees C at d 21) or
      continuously lower temperature T2 (from 28 degrees C at hatching to 21 degrees C
      at d 21) or exposure to cyclically lower temperature T1 (with circadian
      temperature oscillations). Treatments I1 and I2 did not significantly alter
      hatchability compared to control incubation (with 94.8, 95.1, and 92.3%,
      respectively), or hatching BW and overall chick quality. Hatching body
      temperature (Tb) was 0.5 and 0.3 degrees C higher in I1 than in I0 and I2 groups,
      respectively (P = 0.007). A doubled occurrence of health problems was observed
      with T2 condition, regardless of incubation or sex. At d 3, BW was 2% lower with
      treatment I1 than with I0 and I2 and was 3% higher in T1 and T2 groups than in
      T0, but these effects disappeared with age. Group T2 presented a 5% higher feed
      intake than the control group T0 between 3 and 21 d of age (P = 0.025). Feed
      conversion ratio (FCR) was affected by experimental conditions (P < 0.001), with
      low FCR values obtained with I2 incubation in control or cyclically cold
      postnatal conditions. Maximal FCR values were observed in the continuously cold
      postnatal conditions, in males submitted to control incubation and in females
      submitted to I1 incubation, revealing sex-dependent effects of the treatments on
      performance.

PMID- 29053849
TI  - A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on
      the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction
      in Patients with Major Depressive Disorder.
AB  - Background: Major depressive disorder is a common condition that often includes
      cognitive dysfunction. A systematic literature review of studies and a network
      meta-analysis were carried out to assess the relative effect of antidepressants
      on cognitive dysfunction in major depressive disorder. Methods: MEDLINE, Embase,
      Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant
      conference abstracts were searched for randomized controlled trials assessing the
      effects of antidepressants/placebo on cognition. A network meta-analysis
      comparing antidepressants was conducted using a random effects model. Results:
      The database search retrieved 11337 citations, of which 72 randomized controlled
      trials from 103 publications met the inclusion criteria. The review identified 86
      cognitive tests assessing the effect of antidepressants on cognitive functioning.
      However, the Digit Symbol Substitution Test, which targets multiple domains of
      cognition and is recognized as being sensitive to change, was the only test that
      was used across 12 of the included randomized controlled trials and that allowed
      the construction of a stable network suitable for the network meta-analysis. The
      interventions assessed included selective serotonin reuptake inhibitors,
      serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin
      reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network
      meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine
      was the only antidepressant that improved cognitive dysfunction on the Digit
      Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI
      = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was
      statistically more efficacious on the Digit Symbol Substitution Test vs
      escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and
      tricyclic antidepressant classes. Conclusions: This study highlighted the large
      variability in measures used to assess cognitive functioning. The findings on the
      Digit Symbol Substitution Test indicate differential effects of various
      antidepressants on improving cognitive function in patients with major depressive
      disorder.

PMID- 29053850
TI  - Letter: Honorary Authorship in Neurosurgical Literature: A Cross-sectional
      Analysis.

PMID- 29053851
TI  - Escitalopram Ameliorates Hypercortisolemia and Insulin Resistance in Low Birth
      Weight Men With Limbic Brain Alterations.
AB  - Context: Low birth weight (LBW; <2500 g) is linked to the development of insulin
      resistance and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hyperactivity.
      Objective: Our first aim was to study insulin action, LHPA axis function, and
      limbic brain structures in young, healthy LBW men vs normal birthweight (NBW)
      controls (part 1). Our second aim was to investigate the effects of escitalopram
      vs placebo in LBW men in the LHPA axis and insulin sensitivity (part 2). Design
      Setting, Participants, and Intervention: The maximal (Rdmax) and submaximal
      (Rdsubmax) rates of insulin-stimulated glucose turnover, LHPA axis, and brain
      morphology were examined in 40 LBW men and 20 matched NBW men using two-stage
      hyperinsulinemic euglycemic clamp, 24-hour hormone plasma profiles, and magnetic
      resonance imaging. Subsequently, all LBW subjects underwent randomized and double
      blind treatment with escitalopram 20 mg/d or placebo for 3 months followed by a
      complete reexamination. Main Outcome Measures (Part 2): Changes in Rdmax/Rdsubmax
      and plasma-free cortisol 24-hour area under the curve. Results: In LBW vs NBW,
      Rdsubmax and Rdmax were ~16% (P = 0.01) and ~12% (P = 0.01) lower, respectively,
      and 24-hour free cortisol levels were ~20% higher (P = 0.02), primarily driven by
      a ~99% increase at 05:00 am (P < 0.001). Furthermore, these changes were related
      to structural alterations within left thalamus and ventromedial prefrontal
      cortex. However, in LBW men, exposure to escitalopram normalized the free
      cortisol levels and improved the Rdsubmax by ~24% (P = 0.04) compared with
      placebo. Conclusions: LBW vs NBW displayed alterations in key brain structures
      modulating the LHPA axis, elevated free cortisol levels, and insulin resistance.
      Escitalopram administration ameliorated these defects, suggesting a potential for
      LHPA axis modulation compounds to improve insulin action in LBW subjects.

PMID- 29053852
TI  - Genome-wide scan and analysis of positive selective signatures in Dwarf Brown-egg
      Layers and Silky Fowl chickens.
AB  - Chinese domestic chickens have been routinely subjected to artificial selection
      for the production of meats and eggs. Selection results in distinctive signatures
      in the genome that can reveal the genes underlying phenotypes of interest to
      breeders. In this study, we used the Chicken60K SNP chip to analyze DNA from
      Dwarf Brown-egg Layers (DB, n = 203) and Silky Fowls (SF, n = 181) and then
      examined the relative extended haplotype homozygosity (REHH) and fixation index
      (FST) to detect selection signatures. Since population structure analysis showed
      that SF was stratified into 2 subpopulations (SF1 and SF2), we removed the 20 SF1
      chickens, and the remaining individuals (DB and SF2) were scanned for genome-wide
      selection signatures. A total of 939 selection signatures, including 446
      candidate genes, were found to be potential selection targets using the FST test.
      REHH analysis identified 93 and 128 core regions, including 112 and 181 genes, in
      DB and SF2, respectively. Among the candidate genes, domestication-related genes
      such as NELL1 were found. After comparing the candidate genes with the Animal QTL
      database, we identified additional genes possibly associated with growth,
      reproduction, egg laying, and immune response, including GRHL3, CDK1, AKT1, and
      KMD3A. Functional enrichment analysis suggests that genes associated with muscle
      development have undergone positive selection. Our findings provide a genome-wide
      selection signature draft for DB and SF, and establish a resource that can be
      exploited in chicken breeding programs to manipulate the genes that underlie
      desired phenotypes.

PMID- 29053853
TI  - Genome sequence analysis of a distinctive Italian infectious bursal disease
      virus.
AB  - In a recent study, an emerging infectious bursal disease virus (IBDV) genotype
      (ITA) was detected in IBDV-live vaccinated broilers without clinical signs of
      infectious bursal disease (IBD). VP2 sequence analysis showed that strains of the
      ITA genotype clustered separately from vaccine strains and from other IBDV
      reference strains, either classic or very virulent. In order to obtain a more
      exhaustive molecular characterization of the IBDV ITA genotype and speculate on
      its origin, genome sequencing of the field isolate IBDV/Italy/1829/2011,
      previously assigned to the ITA genotype, was performed, and the sequences
      obtained were compared to the currently available corresponding sequences. In
      addition, phylogenetic and recombination analyses were performed. Interestingly,
      multiple amino acid (AA) sequence alignments revealed that the
      IBDV/Italy/1829/2011 strain shared several AA residues with very virulent IBDV
      strains as well as some virulence markers, especially in the VP1 protein.
      Nevertheless, sequence analysis demonstrated the presence of several residues
      typical of IBDV strains at a low degree of virulence in the IBDV/Italy/1829/2011
      strain. Although homologous recombination and reassortant phenomena may occur
      naturally among different IBDV strains, no evidence of those events was found in
      the genome of the IBDV/Italy/1829/2011 strain, which was confirmed to be a
      genetically distinctive IBDV genotype.

PMID- 29053854
TI  - Dietary betaine supplementation increases adrenal expression of steroidogenic
      acute regulatory protein and yolk deposition of corticosterone in laying hens.
AB  - Betaine, an important methyl donor, is known to execute epigenetic regulation of
      gene expression via nutritional reprogramming. Herein, we explore whether feeding
      a betaine-supplemented diet to laying hens would affect corticosteroid
      biosynthesis in the adrenal gland and corticosterone deposition in eggs, in
      correlation with the expression of methyl transfer enzymes and the promoter DNA
      methylation status of affected genes. Rugao yellow-feathered laying hens at 38
      weeks of age were assigned to Control and Betaine groups, fed basal and betaine
      supplemented diets, respectively, for four weeks. Betaine supplementation
      significantly increased (P < 0.05) the average laying rate, while the body weight
      and egg quality remained unchanged. Plasma concentrations of cholesterol and low
      density lipoprotein-cholesterol were also higher (P < 0.05) in the Betaine group.
      Moreover, eggs in the Betaine group contained higher corticosterone in the yolk,
      which was associated with up-regulation of steroidogenesis genes in adrenal
      glands. Steroidogenic acute regulatory protein (StAR), the rate-limiting protein
      responsible for transporting cholesterol to the inner mitochondrial membrane, was
      significantly activated (P < 0.05), together with its transcription factors
      steroidogenic factor-1 (SF-1) and glucocorticoid receptor. Also, betaine
      supplementation significantly up-regulated (P < 0.05) the adrenal mRNA expression
      of adenosyl homocysteinase-like 1 and DNA methyltransferases1 and 3a. Bisulfite
      sequencing analysis revealed significant hypomethylation in several CpG sites
      within the promoter region of SF-1 gene in the adrenal gland. These results
      indicate that dietary supplementation of betaine in hens activates adrenal
      expression of StAR, possibly through epigenetic regulation of SF-1 gene.

PMID- 29053856
TI  - Propolis supplementation attenuates the negative effects of oxidative stress
      induced by paraquat injection on productive performance and immune function in
      turkey poults.
AB  - Paraquat (PQ) is used as a herbicide in agriculture and causes oxidative and
      inflammatory damage to animal tissues. The current study was conducted to
      investigate the positive effects of dietary propolis (PR), as a potent naturally
      produced antioxidant, on growth performance and immune function of turkey poults
      exposed to oxidative stress induced by PQ injection. Native male turkey poults (n
      = 120, 49-d-old) were randomly assigned into 4 groups: poults received a basal
      diet with a daily subcutaneous PQ injection of 5 mg/kg BW for 7 consecutive days
      (PQ group), an experimental diet containing 1 g/kg PR with a daily subcutaneous
      PQ injection for 7 days (PR+PQ group), or received the experimental PR diet with
      a daily subcutaneous injection of 0.5 mL sterile saline for 7 days (PR group);
      while the control poults received a basal diet with a daily subcutaneous saline
      injection for 7 consecutive days (C group). The productive performance in the PQ
      group showed a significant (P < 0.05) reduction in the weight gain (WG) and feed
      intake (FI), and impaired feed conversion ratio (FCR). Propolis supplementation
      in the PR+PQ group significantly ameliorated the PQ effects on WG and FCR. Turkey
      poults of the PQ and PR+PQ groups had a significant augmentation in the blood
      malondialdehyde (MDA), tumor necrosis factor-alpha (TNFalpha), and corticosterone
      levels, and in contrast, a significant reduction in the triiodothyronine (T3),
      when compared to the C group. While propolis significantly reduced the MDA and
      corticosterone, and increased the T3 levels in the PR+PQ group compared to the PQ
      group. Furthermore, the dietary PR supplementation significantly limited the PQ
      suppressive effects on cell- and humoral-mediated immunity and lymphocyte
      proliferation of turkey poults. In addition, propolis supplementation in the PR
      and PR+PQ groups markedly reversed the PQ-induced DNA fragmentation and heat
      shock protein 70 (Hsp70) over-expression in blood cells. It can be concluded that
      PR could improve turkey immunity and performance, particularly under inflammation
      and oxidative stress induced by PQ exposure.

PMID- 29053857
TI  - UV reflection properties of plumage and skin of domesticated turkeys (Meleagris
      gallopavo f. dom.) as revealed by UV photography.
AB  - Reflection and fluorescence properties of feathered and non-feathered body
      regions of white- and bronze-colored fattening turkeys of various ages were
      examined by ultraviolet (UV) photography. The examinations were carried out on 20
      white-feathered fattening turkeys (B.U.T. 6; 10 males, 10 females) and 20 bronze
      feathered fattening turkeys (Grelier 708; 10 males, 10 females) over a period of
      21 weeks. The turkeys were photographed once a wk under long-wave UV (UVA)
      radiation illumination (lambda = 344-407 nm) using a digital camera. A bandpass
      filter was used for UV reflectography to filter out the visible components of the
      used light source. A longpass filter was used for UV fluorescence photography to
      avoid blurring in the image due to chromatic aberration as a result of UV
      illumination. We found that natal down feathers of white-feathered turkeys showed
      an intense yellowish-green fluorescence under UVA light. UVA fluorescence also
      was shown by the natal downs of the slightly melanized plumage areas of bronze
      turkeys. Vaned feathers of white fattening turkeys reflected UVA radiation.
      Freshly molted feathers were optically distinguishable from the previous feather
      generation due to their more intense UVA reflection. In bronze turkeys, both the
      bright end seams of the dark pennaceous feathers and rectrices and the bright
      banding of primary and secondary remiges reflected UVA radiation. Intense UVA
      fluorescence was recognizable in day-old chicks of both color variants on the
      scutellate scales of the legs and toes. In male turkeys of both color variants,
      UVA-reflecting parts were recognizable with increasing age on the featherless
      head region. The UVA-fluorescent and UVA-reflective characteristics of the
      plumage of fattening turkeys were closely related to the plumage color, the
      feather type, the molting state, and the age of the birds. Further research is
      needed regarding the UVA-reflecting properties of the turkey plumage and the
      effects of full-spectrum illumination, including the UVA spectrum, on the
      behavior and health of fattening turkeys.

PMID- 29053855
TI  - Rare GABRA3 variants are associated with epileptic seizures, encephalopathy and
      dysmorphic features.
AB  - Genetic epilepsies are caused by mutations in a range of different genes, many of
      them encoding ion channels, receptors or transporters. While the number of
      detected variants and genes increased dramatically in the recent years,
      pleiotropic effects have also been recognized, revealing that clinical syndromes
      with various degrees of severity arise from a single gene, a single mutation, or
      from different mutations showing similar functional defects. Accordingly, several
      genes coding for GABAA receptor subunits have been linked to a spectrum of benign
      to severe epileptic disorders and it was shown that a loss of function presents
      the major correlated pathomechanism. Here, we identified six variants in GABRA3
      encoding the alpha3-subunit of the GABAA receptor. This gene is located on
      chromosome Xq28 and has not been previously associated with human disease. Five
      missense variants and one microduplication were detected in four families and two
      sporadic cases presenting with a range of epileptic seizure types, a varying
      degree of intellectual disability and developmental delay, sometimes with
      dysmorphic features or nystagmus. The variants co-segregated mostly but not
      completely with the phenotype in the families, indicating in some cases
      incomplete penetrance, involvement of other genes, or presence of phenocopies.
      Overall, males were more severely affected and there were three asymptomatic
      female mutation carriers compared to only one male without a clinical phenotype.
      X-chromosome inactivation studies could not explain the phenotypic variability in
      females. Three detected missense variants are localized in the extracellular GABA
      binding NH2-terminus, one in the M2-M3 linker and one in the M4 transmembrane
      segment of the alpha3-subunit. Functional studies in Xenopus laevis oocytes
      revealed a variable but significant reduction of GABA-evoked anion currents for
      all mutants compared to wild-type receptors. The degree of current reduction
      correlated partially with the phenotype. The microduplication disrupted GABRA3
      expression in fibroblasts of the affected patient. In summary, our results reveal
      that rare loss-of-function variants in GABRA3 increase the risk for a varying
      combination of epilepsy, intellectual disability/developmental delay and
      dysmorphic features, presenting in some pedigrees with an X-linked inheritance
      pattern.

PMID- 29053858
TI  - Ectoparasitism of commercial laying hen by Megninia ginglymura (Megnin) (Acari):
      population dynamic and distribution on the body regions.
AB  - Ectoparasites are temporary or permanent skin dwellers. Megninia ginglymura
      (Megnin) (Analgidae) causes economic damage in commercial poultry farms as a
      result of lower egg production or even death of the host. Little is known about
      Megninia ginglymura's life cycle and infestation. This study aimed to evaluate
      the preference of M. ginglymura for different body regions of the host Gallus
      gallus L. and its abundance and population dynamics in different laying hen
      houses. Samples were collected from August 2013 to August 2014 in three different
      commercial laying hen systems: automatic production systems (A1,2,3);
      semiautomatic systems (S1 (free of pesticides) and S2) and free-range system
      (FR). Ten laying hen were sampled each laying hen house and it were collected
      feathers were collected from different body regions form 10 hens in each laying
      house. A total of 28,305 specimens belonging to M. ginglymura were collected.
      Higher abundance was noted in S1 (9,234), S2 (9,121), and FR (5,873) and lower in
      A2 (2,211), A3 (1,628), and A1 (238). The dorsum (back of the body) region showed
      the highest abundance, mean abundance, and prevalence, representing 29.5% of the
      total specimens collected. The cloacal region was the second with 21.1% of the
      total of this ectoparasite. The abdomen and neck represented 20.8% and 19.6%,
      respectively. The inner wings presented the lowest abundance, mean abundance, and
      prevalence in all laying hen houses (9.0% of specimens). The prevalence was
      significantly different in automatic, semiautomatic, and free-range systems. The
      population peaks seems to coincide with periods of high temperatures and
      precipitation. Populations of this species already exhibit resistance to
      synthetic chemical pesticide.

PMID- 29053859
TI  - Unexpected results when assessing underlying aggressiveness in Japanese quail
      using photocastrated stimulus birds.
AB  - Aggressive behaviors can affect both animal welfare and productivity. Because the
      expression of aggressive behaviors is dependent on the quality of the opponent,
      they reflect relative rather than absolute levels of underlying aggressiveness.
      This study was aimed to characterize the aggressive responsiveness of
      photostimulated (14:10 h light:dark photoperiod) adult Japanese quail when
      interacting with a photocastrated (6:18 h light:dark photoperiod) counterpart in
      a novel test environment and to assesses interindividual variations. This was
      based on the assumption that photocastrated birds will not actively provoke an
      aggressive confrontation. Birds were reared in male-female pairs. Frequencies of
      behaviors (i.e., pecks, threats, chases, grabs, mounts) were determined during 10
      min social interactions in a novel environment. A first experiment evaluated 78
      encounters between a photostimulated male or female with either a photocastrated
      male or female (photocastration of sexually mature birds started at 11 wk of
      age). High interindividual variability was observed and in general, highly
      aggressive birds (performing 20 or more aggressive interactions) received little
      or no aggression from their test counterpart. However, unexpectedly, we also
      found that 37% and 32% of photocastrated males and females, respectively,
      performed aggressions toward their photostimulated counterparts, and initiated
      the aggressive interactions in a similar proportion than photostimulated males.
      Aggressive photocastrated males did not perform reproductive-type behaviors
      (i.e., grabs, mounts). Aggressiveness in the photocastrated birds was attributed
      to their social experience prior to photocastration. Therefore, a second
      experiment evaluated 106 encounters between a photostimulated male or female and
      a naive photocastrated male (photocastration started at 4 wk of age, prior to
      sexual development). Photocastrated males performed no aggressions toward their
      photostimulated counterparts. Consistently with previous studies, our findings
      show that naive photocastrated males can be used as a non-aggressive stimulus
      during a social interaction aimed to assess expression of aggressiveness in
      photostimulated birds. However, caution should be taken when applying the
      photocastration protocol considering that prior fighting and sexual experience or
      other physiological changes related with maturation can interfere during
      subsequent aggressive testing.

PMID- 29053862
TI  - A STUDY OF THE RADIOACTIVITY IN THE DUST STORM EVENT OF APRIL 2015 IN ARABIAN
      PENINSULA.
AB  - Gulf countries are often affected by dust storms which have a significant
      influence on the environment and public health. The present work examines the
      radioactivity content in the intense dust storm occurred over Gulf countries on 1
      April 2015. The results showed that the average value of 137Cs in dust samples
      (+/-SD) is 14.4 +/- 1.6 Bq/kg, which is almost two orders of magnitude larger
      than those in soil samples. 7Be was detected with a considerable amount only in
      dust samples. The activity concentrations of the natural radionuclides (234,238U,
      228,230,232Th, 226,228Ra and 40K) in dust samples were found to be approximately
      two to three times higher than the corresponding values in soil samples, which is
      attributed to the abundance of the finest particle size in the dust samples.
      Also, the activity ratios and the correlations between the detected radionuclides
      were investigated to assess the origin and activities associated with any
      variation of the radionuclides in the environment. Moreover, the total annual
      effective dose due to ingestion of dust was estimated to be 89.7 and 34.9 nSv for
      infants and adults, respectively, which is well below the world average internal
      dose of 290 MUSv. The main contributor to the annual effective dose was 228Ra,
      which contributes ~69.6 and 43.3% for infants and adults, respectively, followed
      by: 226Ra " 232,230,228Th > 234,238U > 40k, 137Cs " 7Be.

PMID- 29053861
TI  - Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged
      and Older Adults With Type 2 Diabetes: The Look AHEAD Study.
AB  - Background: Lifestyle interventions have been shown to improve physical function
      over the short term; however, whether these benefits are sustainable is unknown.
      The long-term effects of an intensive lifestyle intervention (ILI) on physical
      function were assessed using a randomized post-test design in the Look AHEAD
      trial. Methods: Overweight and obese (body mass index >= 25 kg/m2) middle-aged
      and older adults (aged 45-76 years at enrollment) with type 2 diabetes enrolled
      in Look AHEAD, a trial evaluating an ILI designed to achieve weight loss through
      caloric restriction and increased physical activity compared to diabetes support
      and education (DSE), underwent standardized assessments of performance-based
      physical function including a 4- and 400-m walk, lower extremity physical
      performance (expanded Short Physical Performance Battery, SPPBexp), and grip
      strength approximately 11 years postrandomization and 1.5 years after the
      intervention was stopped (n = 3,783). Results: Individuals randomized to ILI had
      lower odds of slow gait speed (<0.8 m/s) compared to those randomized to DSE
      (adjusted OR [95% CI]: 0.84 [0.71 to 0.99]). Individuals randomized to ILI also
      had faster gait speed over 4- and 400-m (adjusted mean difference [95% CI]: 0.019
      [0.007 to 0.031] m/s, p = .002, and 0.023 [0.012 to 0.034] m/sec, p < .0001,
      respectively) and higher SPPBexp scores (0.037 [0.011 to 0.063], p = .005)
      compared to those randomized to DSE. The intervention effect was slightly larger
      for SPPBexp scores among older versus younger participants (0.081 [0.038 to
      0.124] vs 0.013 [-0.021 to 0.047], p = .01). Conclusions: An intensive lifestyle
      intervention has modest but significant long-term benefits on physical function
      in overweight and obese middle-aged and older adults with type 2 diabetes.
      ClinicalTrials.gov Identifier: NCT00017953.

PMID- 29053860
TI  - Clinicopathological correlations in behavioural variant frontotemporal dementia.
AB  - Accurately predicting the underlying neuropathological diagnosis in patients with
      behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge
      for clinicians but will be critical for the success of disease-modifying
      therapies. We sought to improve pathological prediction by exploring
      clinicopathological correlations in a large bvFTD cohort. Among 438 patients in
      whom bvFTD was either the top or an alternative possible clinical diagnosis, 117
      had available autopsy data, including 98 with a primary pathological diagnosis of
      frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four
      with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related
      pathology outside of the motor system. Patients with FTLD were distributed
      between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive
      supranuclear palsy, eight Pick's disease, three frontotemporal dementia with
      parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and
      one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one
      with motor neuron disease, 27 type B including 21 with motor neuron disease,
      eight type C with right temporal lobe presentations, and 11 unclassifiable
      including eight with motor neuron disease), FTLD-FUS (eight patients), and one
      patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that
      stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon
      (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy
      nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least
      'possible' bvFTD diagnostic criteria at first presentation. The frequency of the
      six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP,
      suggesting that these features alone cannot be used to separate patients by major
      molecular class. Voxel-based morphometry revealed that nearly all pathological
      subgroups and even individual patients share atrophy in anterior cingulate,
      frontoinsula, striatum, and amygdala, indicating that degeneration of these
      regions is intimately linked to the behavioural syndrome produced by these
      diverse aetiologies. In addition to these unifying features, symptom profiles
      also differed among pathological subtypes, suggesting distinct anatomical
      vulnerabilities and informing a clinician's prediction of pathological diagnosis.
      Data-driven classification into one of the 10 most common pathological diagnoses
      was most accurate (up to 60.2%) when using a combination of known predictive
      factors (genetic mutations, motor features, or striking atrophy patterns) and the
      results of a discriminant function analysis that incorporated clinical,
      neuroimaging, and neuropsychological data.

PMID- 29053863
TI  - A Case of a Newborn With Blocked RhD Antigen and HDFN.
AB  - A group O RhD-negative pregnant patient with anti-D antibody at titer 1:2048
      delivered a baby boy by cesarean section at 38 + 6 weeks gestational age. The
      neonate typed as group O, but D antigen was at first uncertain. DAT and antibody
      screen of newborn were both positive. Various assays were used for D antigen
      determination. Ultimately, D antigen blocked by high-titer maternal anti-D
      antibody was confirmed. Total bilirubin of the newborn was 52.7 umol/L, and
      hemoglobin was 1.46 mg/dL. O RhD-negative red cells were used for an exchange
      transfusion.

PMID- 29053864
TI  - Damage-associated responses of the host contribute to defence against cyst
      nematodes but not root-knot nematodes.
AB  - When nematodes invade and subsequently migrate within plant roots, they generate
      cell wall fragments (in the form of oligogalacturonides; OGs) that can act as
      damage-associated molecular patterns and activate host defence responses.
      However, the molecular mechanisms mediating damage responses in plant-nematode
      interactions remain unexplored. Here, we characterized the role of a group of
      cell wall receptor proteins in Arabidopsis, designated as polygalacturonase
      inhibiting proteins (PGIPs), during infection with the cyst nematode Heterodera
      schachtii and the root-knot nematode Meloidogyne incognita. PGIPs are encoded by
      a family of two genes in Arabidopsis, and are involved in the formation of active
      OG elicitors. Our results show that PGIP gene expression is strongly induced in
      response to cyst nematode invasion of roots. Analyses of loss-of-function mutants
      and overexpression lines revealed that PGIP1 expression attenuates infection of
      host roots by cyst nematodes, but not root-knot nematodes. The PGIP1-mediated
      attenuation of cyst nematode infection involves the activation of plant camalexin
      and indole-glucosinolate pathways. These combined results provide new insights
      into the molecular mechanisms underlying plant damage perception and response
      pathways during infection by cyst and root-knot nematodes, and establishes the
      function of PGIP in plant resistance to cyst nematodes.

PMID- 29053865
TI  - Beta burst dynamics in Parkinson's disease OFF and ON dopaminergic medication.
AB  - Exaggerated basal ganglia beta activity (13-35 Hz) is commonly found in patients
      with Parkinson's disease and can be suppressed by dopaminergic medication, with
      the degree of suppression being correlated with the improvement in motor
      symptoms. Importantly, beta activity is not continuously elevated, but fluctuates
      to give beta bursts. The percentage number of longer beta bursts in a given
      interval is positively correlated with clinical impairment in Parkinson's disease
      patients. Here we determine whether the characteristics of beta bursts are
      dependent on dopaminergic state. Local field potentials were recorded from the
      subthalamic nucleus of eight Parkinson's disease patients during temporary lead
      externalization during surgery for deep brain stimulation. The recordings took
      place with the patient quietly seated following overnight withdrawal of levodopa
      and after administration of levodopa. Beta bursts were defined by applying a
      common amplitude threshold and burst characteristics were compared between the
      two drug conditions. The amplitude of beta bursts, indicative of the degree of
      local neural synchronization, progressively increased with burst duration.
      Treatment with levodopa limited this evolution leading to a relative increase of
      shorter, lower amplitude bursts. Synchronization, however, was not limited to
      local neural populations during bursts, but also, when such bursts were
      cotemporaneous across the hemispheres, was evidenced by bilateral phase
      synchronization. The probability of beta bursts and the proportion of
      cotemporaneous bursts were reduced by levodopa. The percentage number of longer
      beta bursts in a given interval was positively related to motor impairment, while
      the opposite was true for the percentage number of short duration beta bursts.
      Importantly, the decrease in burst duration was also correlated with the motor
      improvement. In conclusion, we demonstrate that long duration beta bursts are
      associated with an increase in local and interhemispheric synchronization. This
      may compromise information coding capacity and thereby motor processing.
      Dopaminergic activity limits this uncontrolled beta synchronization by
      terminating long duration beta bursts, with positive consequences on network
      state and motor symptoms.

PMID- 29053866
TI  - Impact of litter Salmonella status during feed withdrawal on Salmonella recovery
      from the broiler crop and ceca.
AB  - Research was conducted to evaluate the impact of litter Salmonella status during
      feed withdrawal on Salmonella recovery from the crop and ceca following feed
      withdrawal. In 4 experiments, pens of broilers in separate rooms were challenged
      with marker strains of either Salmonella Montevideo or Salmonella Heidelberg.
      Three d post challenge, a 12-hour feed withdrawal was initiated, and one pen of
      broilers was switched between rooms for each Salmonella serotype. In experiments
      3 and 4, non-challenged broilers also were added to the Salmonella challenge
      pens. The litter of each pen was sampled before and after the feed withdrawal
      period, the broilers euthanized, and the crop and ceca aseptically removed for
      Salmonella isolation. Results showed that only the challenge Salmonella serotype
      was recovered from the litter in challenge pens where broilers were not moved,
      while both Salmonella serotypes were recovered from the litter of the switched
      pens. Salmonella was recovered from 56/80 crops and from 66/80 ceca of challenged
      broilers that remained in the challenge pens. The challenge Salmonella serotype
      was recovered from 50/80 crops and from 60/80 ceca, and the switched pens' litter
      Salmonella serotype was recovered from 19/80 crops but not from the ceca in
      broilers challenged with Salmonella and then switched between pens. For
      experiments 3 and 4, Salmonella was recovered from 19/40 crops and from only 2/40
      ceca from the non-challenged broilers placed into the Salmonella challenge pens.
      The results from broilers that were switched between Salmonella challenge pens
      indicate that the recovery of Salmonella from the crop of broilers following feed
      withdrawal (on Salmonella-contaminated litter) appears to depend mainly on the
      initial challenge Salmonella (62%) and less on the litter Salmonella (24%) status
      during the feed withdrawal period. In contrast, only the initial challenge
      Salmonella was recovered from the ceca (79%) from broilers that remained in
      challenge pens or were switched between Salmonella challenge pens. However, when
      non-challenged broilers were placed into the Salmonella challenge pens and
      commingled during the 12-hour feed and water withdrawal period, it was possible
      to recover the pen litter Salmonella from the ceca at a low level of 5% (2/40).

PMID- 29053867
TI  - Molecular cloning and functional analysis of peafowl (Pavo cristatus) Toll-like
      receptor 7.
AB  - In order to clone the peafowl (Pavo cristatus) Toll-like receptor 7 (TLR7) gene
      and study its biological function, the peafowl TLR7 coding sequences (CDS) were
      amplified by PCR of cDNA from the whole spleen of peafowl. The full-length
      sequence of the peafowl TLR7 gene CDS is 3,141 bp and encodes a 1,046-amino acid
      protein with a classic TLR composition of 16 leucine-rich repeats (LRR).
      Insertions of amino acids were found at position 15 of LRR2, LRR5, LRR7, LRR9,
      LRR11, LRR12, LRR14, and LRR15; and position 10 of LRR11. Reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis showed that the peafowl TLR7 gene was
      highly expressed in lymphoid tissues of the spleen, bursa, bone marrow, lung, and
      peripheral blood mononuclear cells (PBMC). HEK293T cells were transfected with a
      peafowl TLR7 plasmid, and functional analysis showed that peafowl TLR7 could
      respond to R848, leading to activation of NF-kappaB. Following R848 stimulation
      or Newcastle disease virus infection of peafowl PBMC, the levels of IL-1beta, IFN
      gamma, CCLi2, and TGF-beta4 mRNA, assessed by quantitative real-time PCR,
      increased significantly. Triggering peafowl TLR7 results in upregulation of
      inflammatory cytokines and chemokines, suggesting that peafowl TLR7 plays an
      important role in the innate immune response.

PMID- 29053870
TI  - Effects of hydroxychloride and sulfate form of zinc and manganese supplementation
      on superoxide dismutase activity and immune responses post lipopolysaccharide
      challenge in poultry fed marginally lower doses of zinc and manganese.
AB  - Effects of hydroxychloride (OHCl) and sulfate form of zinc and manganese
      supplementation on immune responses of birds fed marginally lower levels of zinc
      and manganese during an experimental lipopolysaccharide (LPS) injection were
      studied. In experiment I, 30-week-old layer birds were fed 50 mg/kg Zn+45 mg/kg
      Mn or 100 mg/kg Zn+90 mg/kg Mn in sulfate or OHCl form and injected with 0 or 500
      MUg/kg LPS in a 2 (50 mg Zn+45 mg Mn and 100 mg Zn+90 mg Mn) X 2 (sulfate and
      OHCl) X 2 (0 and 500 MUg LPS) factorial setup of treatments for 10 weeks. Among
      LPS-injected birds, those receiving 50 mg ZnOHCl+45 mg MnOHCl had comparable
      heterophil and monocyte superoxide dismutase (SOD) activity compared to the birds
      fed 100 mg Zn+90 mg Mn. Compared to the birds injected with PBS, LPS injection
      upregulated cathelicidin and IL-1 relative mRNA amounts in monocytes from birds
      fed 100 mg Zn+90 mg Mn, both in sulfate and OHCl form, and in birds fed 50 mg
      ZnOHCl+45 mg MnOHCl, but not in the birds fed 50 mg ZnSO4+45 mg MnSO4. In
      experiment II, one-day-old broiler birds were fed 50 mg ZnOHCl+45 mg MnOHCl, 50
      mg ZnOHCl+90 mg MnOHCl, 100 mg ZnOHCL+45 mg MnOHCl, 100 mg ZnOHCl+90 mg MnOHCl,
      50 mg ZnSO4+45 mg MnSO4, or 100 mg ZnSO4+90 mg MnSO4 for 21 and 42 days. Birds
      fed 100 mg ZnOHCl+45 mg MnOHCl form had a comparable heterophil and monocyte SOD
      activity and monocyte cathelicidin mRNA amounts compared to the group fed 100 mg
      Zn+90 mg Mn. Increasing the ZnOHCl content from 50 mg to 100 mg/kg Zn reversed (P
      > 0.05) the decrease in SOD activity and monocyte cathelicidin mRNA levels of the
      50 mg ZnOHCl+45 mg MnOHCL fed group, and increasing the MnOHCl content from 45 mg
      to 90 mg/kg in the 100 mg ZnOHCl+45 mg MnOHCl group further increased SOD
      activity. In conclusion, birds fed diets with lower amounts of zinc and manganese
      in sulfate form decreased SOD activity and IL-1 and cathelicidin amounts during
      inflammation, and either increasing the dietary zinc and manganese content or
      feeding zinc and manganese in OHCl form synergistically increased the SOD
      activity and IL-1 and cathelicidin mRNA amounts in immune cells.

PMID- 29053869
TI  - Enzymatic hydrolysis of fumonisins in the gastrointestinal tract of broiler
      chickens.
AB  - Fumonisins (FB) are among the most frequently detected mycotoxins in feedstuffs
      and finished feed, and recent data suggest that the functions of the
      gastrointestinal tract (GIT) in poultry species might be compromised at doses
      ranging from 10 to 20 mg/kg, close to field incidences and below the US and EU
      guidelines. Strategies are therefore necessary to reduce the exposure of poultry
      to FB. In the present study, we assessed the efficacy of fumonisin esterase FumD
      (EC 3.1.1.87, commercial name FUMzyme(r)) to cleave the tricarballylic acid side
      chains of FB, leading to the formation of non-toxic hydrolyzed fumonisins in the
      GIT of broiler chickens. Broiler chickens were fed for 14 d (7 to 21 d of age) 3
      different diets (6 birds/cage, 6 cages/diet), i) control feed (negative control
      group), ii) feed contaminated with 10 mg FB/kg (FB group), and iii) feed
      contaminated with 10 mg FB/kg and supplemented with 100 units of FUMzyme(r)/kg
      (FB+FUMzyme(r) group). To determine the degree of reduction of FB in the GIT, 2
      characteristics were analyzed. First, the sphinganine-to-sphingosine ratio in the
      serum and liver was determined as a biomarker of effect for exposure to FB.
      Second, the concentration of fumonisin B1 and its hydrolyzed forms was evaluated
      in the gizzard, the proximal and distal parts of the small intestine, and the
      excreta. Significantly reduced sphinganine-to-sphingosine ratios in the serum and
      liver of the FB+FUMzyme(r) group (serum: 0.15 +/- 0.01; liver: 0.17 +/- 0.01)
      compared to the FB group (serum: 0.20 +/- 0.01; liver: 0.29 +/- 0.03) proved that
      supplementation of broiler feed with FUMzyme(r) was effective in partially
      counteracting the toxic effect of dietary FB. Likewise, FB concentrations in
      digesta and excreta were significantly reduced in the FB+FUMzyme(r) group
      compared to the FB group (P < 0.05; up to 75%). FUMzyme(r) furthermore partially
      counteracted FB-induced up-regulation of cytokine gene expression (IL-8 and IL
      10) in the jejunum. The FB group showed significantly higher gene expression of
      IL-8 and IL-10 compared to the negative control group (IL-8: fold change = 2.9 +/
      1.1, P < 0.05; IL-10: fold change = 3.6 +/- 1.4, P < 0.05), whereas IL-8 and IL
      10 mRNA levels were not significantly different in the FB+FUMzyme(r)(r) group
      compared to the other 2 groups. In conclusion, FUMzyme(r) is suitable to detoxify
      FB in chickens and maintain gut functions.

PMID- 29053871
TI  - Cellular and morphological characterization of blastoderms from freshly laid
      broiler eggs.
AB  - The pioneering study of Eyal-Giladi and Kochav (EG&K; Eyal-Giladi and Kochav,
      1976) on the early developmental stages-from fertilization, through oviposition,
      to the gastrulation process-set the standard for characterizing chicken embryos,
      and has been used in numerous studies over the years. During uterine development,
      the chicken embryo undergoes dramatic changes, extremely rapid cell cycles,
      massive cell death, and axial determination processes. However, once the egg is
      laid, the temperature drops and the embryo enters into a diapause-like state.
      This phenomenon is utilized to store fertile eggs prior to incubation. The
      ability to resume development to hatching, following storage, relies on several
      factors, including the number of living cells and the embryonic developmental
      stage. These factors are highly influenced by the storage conditions-mainly
      duration and temperature. Thus, to study the effects of storage conditions on
      embryonic viability, a comprehensive characterization of the starting point
      shortly after oviposition-is needed. In this study, we characterized freshly laid
      broiler eggs from Ross 308 flocks for embryonic developmental stage, total cell
      count, and cell viability. Using the novel high-resolution episcopic microscopy
      (HREM) system, we show, for the first time, high-resolution 3D morphological
      models of blastoderms which allow for highly accurate embryonic staging. Staging
      was also done under a dissecting microscope thus allowing for a direct side-by
      side comparison of the two methods. Analysis of freshly laid blastomeres showed
      that the total nucleus count increases with developmental stage from ~60,000 at
      stage X EG&K to ~130,000 at stage XIII EG&K, whereas the proportion of mitotic
      index and dying cells at oviposition are ~2% and ~5%, respectively. Moreover,
      staging embryos from young and old flocks revealed that the blastoderms of the
      old flocks are more developed. Specifically, the predominant embryonic stages
      were XI and XII EG&K in young and old flocks, respectively. Collectively, we
      characterized parameters that can serve to analyze the maladaptive effects of
      prolonged storage under various conditions on embryo survival.

PMID- 29053868
TI  - LAGOS-NE: a multi-scaled geospatial and temporal database of lake ecological
      context and water quality for thousands of US lakes.
AB  - Understanding the factors that affect water quality and the ecological services
      provided by freshwater ecosystems is an urgent global environmental issue.
      Predicting how water quality will respond to global changes not only requires
      water quality data, but also information about the ecological context of
      individual water bodies across broad spatial extents. Because lake water quality
      is usually sampled in limited geographic regions, often for limited time periods,
      assessing the environmental controls of water quality requires compilation of
      many data sets across broad regions and across time into an integrated database.
      LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US
      states.LAGOS-NE contains data for 51 101 lakes and reservoirs larger than 4 ha in
      17 lake-rich US states. The database includes 3 data modules for: lake location
      and physical characteristics for all lakes; ecological context (i.e., the land
      use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in
      situ measurements of lake water quality for a subset of the lakes from the past 3
      decades for approximately 2600-12 000 lakes depending on the variable. The
      database contains approximately 150 000 measures of total phosphorus, 200 000
      measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality
      data were compiled from 87 lake water quality data sets from federal, state,
      tribal, and non-profit agencies, university researchers, and citizen scientists.
      This database is one of the largest and most comprehensive databases of its type
      because it includes both in situ measurements and ecological context data.
      Because ecological context can be used to study a variety of other questions
      about lakes, streams, and wetlands, this database can also be used as the
      foundation for other studies of freshwaters at broad spatial and ecological
      scales.

PMID- 29053872
TI  - Resveratrol alleviates heat stress-induced impairment of intestinal morphology,
      microflora, and barrier integrity in broilers.
AB  - This study was to investigate the effect of resveratrol on intestinal morphology,
      microfloras, and barrier integrity of broilers subjected to heat stress. Two
      hundred-seventy 21-day-old Cobb male broilers were randomly allocated to 3
      treatment groups, each of which included 6 replicates with 15 birds per
      replicate. The 3 treatment groups were as follows: the control group, in which
      birds were exposed to thermoneutral condition (22 +/- 1 degrees C), and the heat
      stress group and heat stress + resveratrol (400 mg/kg) group, in which birds were
      exposed to cyclic heat stress (33 +/- 1 degrees C for 10 h/d from 0800 to 1800 h
      and 22 +/- 1 degrees C for the remaining time. Compared with birds in the control
      group, birds in the heat stress group exhibited decreased (P < 0.05) final body
      weight, average daily gain, average daily feed intake, villus height, villus
      height to crypt depth ratio, goblet cells numbers, populations of Lactobacillus
      and Bifidobacterium, and mRNA levels of mucin-2, claudin-1, occludin, zona
      occludens-1, and E-cadherin, and increased (P < 0.05) crypt depth, serum D-lactic
      acid and fluorescein isothiocyanate dextran contents and diamine oxidase
      activity, and populations of Salmonella, Escherichia coli, and Clostridium.
      Compared with birds in the heat stress group, birds in the heat stress +
      resveratrol group exhibited decreased (P < 0.05) crypt depth, serum D-lactic acid
      and fluorescein isothiocyanate dextran contents, and populations of Escherichia
      coli, and increased (P < 0.05) final body weight, villus height, villus height to
      crypt depth ratio, goblet cells numbers, populations of Lactobacillus and
      Bifidobacterium, and mRNA levels of mucin-2, claudin-1, occludin, and E-cadherin.
      Taken together, these results indicated for the first time that dietary addition
      of resveratrol was effective in partially ameliorating the adverse effects of
      heat stress on intestinal barrier function in broilers by restoring the impaired
      villus-crypt structure, modifying the profiles of intestinal microfloras, and
      altering the mRNA expression of intestinal tight junctions- and adherence
      junctions-related genes.

PMID- 29053873
TI  - Exercise for the Prevention of Low Back Pain: Systematic Review and Meta-Analysis
      of Controlled Trials.
AB  - The aim of this systematic review and meta-analysis was to assess the effect of
      exercise in population-based interventions to prevent low back pain (LBP) and
      associated disability. Comprehensive literature searches were conducted in
      multiple databases, including PubMed, Embase, and the Cochrane Library, from
      their inception through June 2017. Thirteen randomized controlled trials (RCTs)
      and 3 nonrandomized controlled trials (NRCTs) qualified for the meta-analysis.
      Exercise alone reduced the risk of LBP by 33% (risk ratio = 0.67, 95% confidence
      interval: 0.53, 0.85; I2 = 23%, 8 RCTs, n = 1,634), and exercise combined with
      education reduced it by 27% (risk ratio = 0.73, 95% confidence interval: 0.59,
      0.91; I2 = 6%, 6 trials, n = 1,381). The severity of LBP and disability from LBP
      were also lower in exercise groups than in control groups. Moreover, results were
      not changed by excluding the NRCTs or adjusting for publication bias. Few trials
      assessed health-care consultation or sick leave for LBP, and meta-analyses did
      not show statistically significant protective effects of exercise on those
      outcomes. Exercise reduces the risk of LBP and associated disability, and a
      combination of strengthening with either stretching or aerobic exercises
      performed 2-3 times per week can reasonably be recommended for prevention of LBP
      in the general population.

PMID- 29053875
TI  - Current State of the Surgical Treatment of Terminal Neuromas.
AB  - Painful terminal neuromas resulting from nerve injury following amputation are
      common. However, there is currently no universally accepted gold standard of
      treatment for this condition. A comprehensive literature review is presented on
      the treatment of terminal neuromas. Four categories of terminal neuroma surgical
      procedures are assessed: epineurial closure; nerve transposition with
      implantation; neurorrhaphy, and alternate target reinnervation. Significant
      patient and case studies are highlighted in each section, focusing on surgical
      technique and patient outcome metrics. Studies presented consisted of a PubMed
      search for "terminal neuromas," without year limitation. The current available
      research supports the use of implantation into muscle for the surgical treatment
      of terminal neuromas. However, this technique has several fundamental flaws that
      limit its utility, as it does not address the underlying physiology behind
      neuroma formation. Regenerative peripheral nerve interfaces and targeted muscle
      reinnervation are 2 techniques that seem to offer the most promise in preventing
      and treating terminal neuroma formation. Both techniques are also capable of
      generating control signals which can be used for both motor and sensory
      prosthetic control. Such technology has the potential to lead to the future
      restoration of lost limb function in amputees. Further clinical research
      employing larger patient groups with high-quality control groups and reproducible
      outcome measures is needed to determine the most effective and beneficial
      surgical treatment for terminal neuromas. Primary focus should be placed on
      investigating techniques that most closely approximate the theoretically ideal
      neuroma treatment, including targeted muscle reinnervation and regenerative
      peripheral nerve interfaces.

PMID- 29053874
TI  - Tau pathology and neurodegeneration contribute to cognitive impairment in
      Alzheimer's disease.
AB  - Neuropathological and in vivo studies have revealed a tight relationship between
      tau pathology and cognitive impairment across the Alzheimer's disease spectrum.
      However, tau pathology is also intimately associated with neurodegeneration and
      amyloid pathology. The aim of the present study was therefore to assess whether
      grey matter atrophy and amyloid pathology contribute to the relationship between
      tau pathology, as measured with 18F-AV-1451-PET imaging, and cognitive deficits
      in Alzheimer's disease. We included 40 amyloid-positive patients meeting criteria
      for mild cognitive impairment due to Alzheimer's disease (n = 5) or probable
      Alzheimer's disease dementia (n = 35). Twelve patients additionally fulfilled the
      diagnostic criteria for posterior cortical atrophy and eight for logopenic
      variant primary progressive aphasia. All participants underwent 3 T magnetic
      resonance imaging, amyloid (11C-PiB) positron emission tomography and tau (18F-AV
      1451) positron emission tomography, and episodic and semantic memory, language,
      executive and visuospatial functions assessment. Raw cognitive scores were
      converted to age-adjusted Z-scores (W-scores) and averaged to compute composite
      scores for each cognitive domain. Independent regressions were performed between
      18F-AV-1451 binding and each cognitive domain, and we used the Biological
      Parametric Mapping toolbox to further control for local grey matter volumes, 11C
      PiB uptake, or both. Partial correlations and causal mediation analyses
      (mediation R package) were then performed in brain regions showing an association
      between cognition and both 18F-AV-1451 uptake and grey matter volume. Our results
      showed that decreased cognitive performance in each domain was related to
      increased 18F-AV-1451 binding in specific brain regions conforming to established
      brain-behaviour relationships (i.e. episodic memory: medial temporal lobe and
      angular gyrus; semantic memory: left anterior temporal regions; language: left
      posterior superior temporal lobe and supramarginal gyrus; executive functions:
      bilateral frontoparietal regions; visuospatial functions: right more than left
      occipitotemporal regions). This pattern of regional associations remained
      essentially unchanged-although less spatially extended-when grey matter volume or
      11C-PiB uptake maps were added as covariates. Mediation analyses revealed both
      direct and grey matter-mediated effects of 18F-AV-1451 uptake on cognitive
      performance. Together, these results show that tau pathology is related in a
      region-specific manner to cognitive impairment in Alzheimer's disease. These
      regional relationships are weakly related to amyloid burden, but are in part
      mediated by grey matter volumes. This suggests that tau pathology may lead to
      cognitive deficits through a variety of mechanisms, including, but not restricted
      to, grey matter loss. These results might have implications for future
      therapeutic trials targeting tau pathology.

PMID- 29053876
TI  - Blood Hematological and Biochemical Constituents, Antioxidant Enzymes, Immunity
      and Lymphoid Organs of Broiler Chicks Supplemented with Propolis, Bee Pollen and
      Mannan Oligosaccharides Continuously or Intermittently.
AB  - This study investigate the effect of bee pollen (BP) and/or propolis (Pro) as an
      alternative to Mannan oligosaccharides (Bio-MOS, a hydrolyzed yeast with natural
      and artificial flavors Alltech Inc) when given continuously or intermittently on
      antioxidant enzymes, immunity, weight and morphology of lymphoid organs of
      broilers. Thus, 324 unsexed one-day-old Arbor Acres broilers were randomly
      distributed into nine treatment groups, each replicated 6 times of 6 birds per
      replicate. The chicks were kept in wire cages and fed the same basal diet and
      were submitted to the following treatments: control without supplementation
      (control) or supplemented with BP at 300 mg, Pro at 300 mg, BP+Pro at 300 mg each
      and Bio-MOS at 0.5 g/kg diet. Each supplemented group was subdivided into two
      subgroups in which the additives were supplied continuously or intermittently. In
      the continuously supplemented groups, supplementations were given from one till
      36 days of age, and in the intermittently supplemented groups, the administration
      was only three days before, on the day of and day after vaccination. The BP and
      Pro supplied continuously or intermittently was equally potent for improving
      immunity, antioxidant enzymes similar to Bio-MOS. All supplements supplied either
      continuously or intermittently resulted a significantly higher thymus (P < .04)
      and bursa weights (P < .001) than the control group. Combining BP with Pro
      resulted in a further increase in thymus weights and small follicle diameter
      compared to the control group. In addition, thymus percentage in the group
      received BP+Pro showed a further increase compared to the control and Pro
      supplemented intermittently. Bio-MOS, when supplied continuously or
      intermittently, resulted in the greatest response in splenic lymphoblasts.
      Supplementation with either BP or Pro intermittently, is adequate to promote
      health and immune response of broiler chicks, with 40% saving of supplementation
      costs.

PMID- 29053878
TI  - Neuromuscular Ultrasound: A call for training and education.

PMID- 29053879
TI  - Decrement with high frequency repetitive nerve stimulation in a RAPSN congenital
      myasthenic syndrome.

PMID- 29053877
TI  - Transient receptor potential vanilloid 4 channel regulates vascular endothelial
      permeability during colonic inflammation in dextran sulphate sodium-induced
      murine colitis.
AB  - BACKGROUND AND PURPOSE: The transient receptor potential vanilloid 4 (TRPV4)
      channel is a non-selective cation channel involved in physical sensing in various
      tissue types. The present study aimed to elucidate the function and expression of
      TRPV4 channels in colonic vascular endothelial cells during dextran sulphate
      sodium (DSS)-induced colitis. EXPERIMENTAL APPROACH: The role of TRPV4 channels
      in the progression of colonic inflammation was examined in a murine DSS-induced
      colitis model using immunohistochemical analysis, Western blotting and Evans blue
      dye extrusion assay. KEY RESULTS: DSS-induced colitis was significantly
      attenuated in TRPV4-deficient (TRPV4 KO) as compared to wild-type mice. Repeated
      intrarectal administration of GSK1016790A, a TRPV4 agonist, exacerbated the
      severity of DSS-induced colitis. Bone marrow transfer experiments demonstrated
      the important role of TRPV4 in non-haematopoietic cells for DSS-induced colitis.
      DSS treatment up-regulated TRPV4 expression in the vascular endothelia of colonic
      mucosa and submucosa. DSS treatment increased vascular permeability, which was
      abolished in TRPV4 KO mice. This DSS-induced increase in vascular permeability
      was further enhanced by i.v. administration of GSK1016790A, and this effect was
      abolished by the TRPV4 antagonist RN1734. TRPV4 was co-localized with vascular
      endothelial (VE)-cadherin, and VE-cadherin expression was decreased by repeated
      i.v. administration of GSK1016790A during colitis. Furthermore, GSK106790A
      decreased VE-cadherin expression in mouse aortic endothelial cells exposed to TNF
      alpha. CONCLUSION AND IMPLICATIONS: These findings indicate that an up-regulation
      of TRPV4 channels in vascular endothelial cells contributes to the progression of
      colonic inflammation by increasing vascular permeability. Thus, TRPV4 is an
      attractive target for the treatment of inflammatory bowel diseases.

PMID- 29053880
TI  - Electrodiagnostic errors contribute to chronic inflammatory demyelinating
      polyneuropathy misdiagnosis.
AB  - INTRODUCTION: Documentation of peripheral nerve demyelination is an important
      part of the chronic inflammatory demyelinating polyneuropathy (CIDP) diagnostic
      process. METHODS: We performed a retrospective analysis of patients referred with
      a diagnosis of CIDP who were found to have a different condition.
      Electrodiagnostic study data and interpretations formulated at the time of the
      initial diagnosis were compared to those obtained during the reevaluation.
      RESULTS: Thirty-nine of 86 patients were found not to have CIDP. Initial
      electrodiagnostic data quality was generally acceptable, but initial
      electrodiagnostic conclusions were confirmed in only 45% of misdiagnosed studies.
      DISCUSSION: Vulnerability to interpretive errors increases when amplitude
      dependent slowing occurs with length-dependent axonal neuropathies or motor
      neuron disease, amplitude-independent slowing occurs in diabetic patients,
      fibular nerve to extensor digitorum brevis (EDB) muscle findings are the focal
      diagnostic abnormality, conduction block is absent, conduction velocity (CV)
      slowing is limited to compressible sites, and accurate electrodiagnostic
      interpretations are dismissed in favor of equivocal clinical and cerebrospinal
      fluid findings. Muscle Nerve 57: 542-549, 2018.

PMID- 29053881
TI  - HIV, antiretrovirals, and peripheral neuropathy: A moving target.

PMID- 29053882
TI  - Electrodiagnostic studies in the intensive care unit: A comparison study 2
      decades later.
AB  - INTRODUCTION: Since the late 1980s, critical illness myopathy (CIM) and critical
      illness polyneuropathy (CIP) have been increasingly recognized in the intensive
      care unit (ICU). We explored whether these causes of ICU weakness were now more
      likely to lead to electrodiagnostic studies (EDX) at our institution than they
      were 19-20 years earlier. METHODS: We reviewed 100 consecutive ICU patients who
      underwent EDX from 2009 to 2015 and compared them to a previously reported study
      population from 1990-1995. RESULTS: Thirty-seven (39%) had CIM, CIP, or both
      versus 55% in the previous study (P = 0.04). Thirty-four (36%) were diagnosed
      with "traditional" pre-ICU causes of weakness, such as motor neuron disease or
      Guillain-Barre syndrome, versus 29% in the earlier study (P = 0.3). DISCUSSION:
      CIM and CIP continue to be common disorders that lead to ICU EDX, but their
      proportion declined compared with 19-20 years earlier, possibly due to the
      perceived role and selective use of EDX in the ICU. Muscle Nerve 57: 772-776,
      2018.

PMID- 29053884
TI  - Looking into cognitive impairment in primary-progressive multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Cognitive impairment in primary-progressive multiple
      sclerosis (PP-MS) is correlated with global brain atrophy. Unfortunately, brain
      volume computation requires processing resources that are not widely available in
      clinical practice. Therefore, we decided to test the predictive role of retinal
      atrophy metrics on cognitive decline, applying them as a proxy of gray matter
      atrophy in PP-MS. METHODS: Twenty-five patients with PP-MS completed the Brief
      International Cognitive Assessment for Multiple Sclerosis and underwent spectral
      domain optical coherence tomography (OCT) and 3.0-T magnetic resonance imaging.
      We tested, through a stepwise logistic regression, whether OCT metrics [retinal
      nerve fiber layer, ganglion cell + inner plexiform layer (GCIPL) and total
      macular volume] predicted cognitive impairment and explored the role of gray
      matter atrophy in mediating these correlations. RESULTS: Among OCT metrics, only
      GCIPL was associated with cognitive impairment (rp = 0.448, P = 0.036) and
      predictive of objective cognitive impairment (Wald [1] = 4.40, P = 0.036).
      Controlling for demographics, normalized brain volume and thalamic volume were
      correlated with GCIPL (rp = 0.427, P = 0.047 and rp = 0.674, P = 0.001,
      respectively) and cognitive scores (rp = 0.593, P = 0.004 and rp = 0.501, P =
      0.017, respectively), with thalamic volume nearly mediating the association
      between GCIPL and cognition (Sobel z = 1.86, P = 0.063). CONCLUSIONS: The GCIPL
      thickness is a suitable measure of neurodegeneration. In comparison with brain
      atrophy, GCIPL offers higher histopathological specificity, being a pure
      correlate of neuronal loss, and may be a non-invasive, easy-to-perform way to
      quantitatively evaluate and monitor neuronal loss related to cognitive impairment
      in PP-MS.

PMID- 29053883
TI  - Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the
      Thoroughbred horse: Differentiating cobalt abuse from supplementation.
AB  - BACKGROUND: While cobalt is an essential micronutrient for vitamin B12 synthesis
      in the horse, at supraphysiological concentrations, it has been shown to enhance
      performance in human subjects and rats, and there is evidence that its
      administration in high doses to horses poses a welfare threat. Animal sport
      regulators currently control cobalt abuse via international race day thresholds,
      but this work was initiated to explore means of potentially adding to application
      of those thresholds since cobalt may be present in physiological concentrations.
      OBJECTIVES: To devise a scientific basis for differentiation between presence of
      cobalt from bona fide supplementation and cobalt doping through the use of
      ratios. STUDY DESIGN: Six Thoroughbred horses were given 10 mL vitamin B12
      /cobalt supplement (Hemo-15(r) ; Vetoquinol, Buckingham, Buckinghamshire, UK.,
      1.5 mg B12 , 7 mg cobalt gluconate = 983 MUg total Co) as an i.v. bolus then an
      i.v. infusion (15 min) of 100 mg cobalt chloride (45.39 mg Co) 6 weeks later. Pre
      and post-administration plasma and urine samples were analysed for cobalt and
      vitamin B12 . METHODS: Urine and plasma samples were analysed for vitamin B12
      using an immunoassay and cobalt concentrations were measured via ICP-MS. Baseline
      concentrations of cobalt in urine and plasma for each horse were subtracted from
      their cobalt concentrations post-administration for the PK analysis.
      Compartmental analysis was used for the determination of plasma PK parameters for
      cobalt using commercially available software. RESULTS: On administration of a
      vitamin B12 /cobalt supplement, the ratio of cobalt to vitamin B12 in plasma
      rapidly increased to approximately 3 and then rapidly declined below a ratio of 1
      and then back to near baseline over the next week. On administration of 100 mg
      cobalt chloride, the ratio initially exceeded 10 in plasma and then declined with
      the lower 95% confidence interval remaining above a ratio of 1 for 7 days. For
      two horses with extended sampling, the plasma ratio remained above one for
      approximately 28 days after cobalt chloride administration. The effect of the
      administration of the vitamin B12 /cobalt supplement on the urine ratio was
      transient and reached a peak value of 10 which then rapidly declined. However, a
      urine ratio of 10 was exceeded, with the lower 95% confidence interval remaining
      above a ratio of 10 for 7 days after cobalt chloride administration. For the two
      horses with extended sampling, the urine ratio remained above 10 for about 18
      days (442 h) after cobalt chloride administration even though the absolute cobalt
      urine concentration had dropped below the international threshold of 100 ng/mL
      after 96 h. MAIN LIMITATIONS: Only one vitamin B12 /cobalt product was evaluated,
      a limited number of horses were included, the horses were not in full race
      training and the results may be specific to this population of horses.
      CONCLUSIONS: The results provide the basis for a potential strategy for allowing
      supplementation with vitamin B12 products, while controlling the misuse of high
      doses of cobalt, through a combination of international thresholds and ratios of
      cobalt to vitamin B12 , in plasma and urine.

PMID- 29053885
TI  - Cortical superficial siderosis and acute convexity subarachnoid hemorrhage in
      cerebral amyloid angiopathy.
AB  - BACKGROUND AND PURPOSE: Acute convexity subarachnoid hemorrhage (cSAH) and
      cortical superficial siderosis (cSS) are neuroimaging markers of cerebral amyloid
      angiopathy (CAA) that may arise through similar mechanisms. The prevalence of cSS
      in patients with CAA presenting with acute cSAH versus lobar intracerebral
      hemorrhage (ICH) was compared and the physiopathology of cSS was explored by
      examining neuroimaging associations. METHODS: Data from 116 consecutive patients
      with probable CAA (mean age, 77.4 +/- 7.3 years) presenting with acute cSAH (n =
      45) or acute lobar ICH (n = 71) were retrospectively analyzed. Magnetic resonance
      imaging scans were analyzed for cSS and other imaging markers. The two groups'
      clinical and imaging data were compared and the associations between cSAH and cSS
      were explored. RESULTS: Patients with cSAH presented mostly with transient focal
      neurological episodes. The prevalence of cSS was higher amongst cSAH patients
      than amongst ICH patients (88.9% vs. 57.7%; P < 0.001). In multivariable logistic
      regression analysis, focal [odds ratio (OR) 6.73; 95% confidence interval (CI)
      1.75-25.81; P = 0.005] and disseminated (OR 11.68; 95% CI 3.55-38.35; P < 0.001)
      cSS were independently associated with acute cSAH, whereas older age (OR 0.93;
      95% CI 0.87-0.99; P = 0.025) and chronic lobar ICH count (OR 0.45; 95% CI 0.25
      0.80; P = 0.007) were associated with acute lobar ICH. CONCLUSIONS: Amongst
      patients with CAA, cSS is independently associated with acute cSAH. These
      findings suggest that cSAH may be involved in the pathogenesis of the cSS
      observed in CAA. Longitudinal studies are warranted to assess this potential
      causal relationship.

PMID- 29053886
TI  - A historical perspective and evolution of the treatment of male urinary
      incontinence.
AB  - AIMS: To describe the historical changes from antiquity until present in the
      presentation and treatment of male urinary incontinence. METHODS: A literature
      review of PubMed articles in English pertaining to male incontinence was
      performed. RESULTS: Male urinary incontinence was first mentioned in Egyptian
      manuscripts in 1500 B.C. In 1564, Ambroise Pare designed portable urinals for
      incontinent males. Wilhem Hildanus created the first condom catheter with pig
      bladder in the 1600s and was also credited with fashioning the first penile
      clamp. Lorenz Heister introduced a perineal bulbar urethral compression belt in
      1747 which would provide the blueprint for air-inflated bulbar urethral
      compression devices such as the one designed by S.A. Vincent in 1960. Robert
      Gersuny performed the first periurethral paraffin injection bulking therapy in
      the late 19th century. In 1929, Frederic Foley introduced the modern catheter,
      and also credited with conception of the first artificial sphincter. From 1970 to
      1973, Joseph Kaufman surgically created bulbar compression for post-prostatectomy
      incontinence, but not before designing the first male sling with John Berry in
      1958. In 1973, F. Brantley Scott introduced the first multi-component artificial
      inflatable sphincter. Improvements upon periurethral bulking therapy occurred
      rapidly in the late 20th century with Teflon, collagen, autologous adipose,
      tissue and cross-linked silicone gels. Since 2007, stem cell injection therapy
      has emerged as a new therapeutic option for incontinence; however, results are
      mixed and remains experimental. CONCLUSION: Treatment for male urinary
      incontinence has evolved from noninvasive devices to various surgical procedures.
      Artificial sphincters remain the gold-standard therapy for male urinary
      incontinence.

PMID- 29053887
TI  - Low FoxG1 and high Olig-2 labelling indices define a prognostically favourable
      subset in isocitrate dehydrogenase (IDH)-mutant gliomas.
AB  - AIMS: Previous data suggest that expression of transcription factors FoxG1 and
      Olig-2 can separate hotspot histone H3 family member 3A (H3F3A)-mutant tumours in
      paediatric glioma. We evaluated their prognostic potential and feasibility for
      identifying H3F3A-mutant tumours among IDH-mutant/wild-type gliomas. METHODS:
      Immunohistochemistry of FoxG1/Olig-2 and alpha-thalassaemia/mental-retardation
      syndrome-X-linked gene (ATRX) in 471 cases of diffuse gliomas and molecular
      determination of IDH, H3F3A, MGMT and 1p/19 codeletion status. RESULTS: Mean
      percentage of FoxG1-positive tumour cells increased from 17% in WHO grade II to
      over 21% in grade III to 37% in grade IV tumours, whereas mean Olig-2 indices
      decreased from 29% to 28% to 17% respectively. FoxG1 indices were similar in
      astrocytic and oligodendroglial tumours, whereas Olig-2 indices were increased in
      oligodendrogliomas compared to astrocytic tumours (n = 451, P < 0.0001). FoxG1
      positive nuclei were significantly reduced in IDH and H3F3A K27-mutant tumours,
      whereas Olig-2-positive nuclei were significantly reduced in IDH-wild-type and
      H3F3A G34-mutant tumours. Among IDH-mutant tumours, mean Olig-2 index was
      significantly higher in 1p/19q codeleted tumours (mean: 43%) compared to IDH
      mutant tumours with ATRX loss (mean: 23%, P < 0.0001). A significantly better
      outcome was first suggested for FoxG1low tumours (n = 212, log rank P = 0.0132)
      and Olig-2high tumours (n = 203, log-rank P = 0.0011) based on classification and
      regression tree determined cutoffs, but this was not confirmed by multivariate
      analysis including IDH mutation, WHO grade, ATRX status and age. CONCLUSIONS:
      While the combined FoxG1/Olig-2 profile may discriminate H3F3A K27- and G34
      mutant tumours and define a prognostically favourable subset in IDH-mutant
      gliomas, our data show that labelling indices of these transcription factors
      overlap with adult IDH-mutant and wild-type tumour classes.

PMID- 29053888
TI  - Epidemiological patterns of tick-borne encephalitis in Lithuania and clinical
      features in adults in the light of the high incidence in recent years: a
      retrospective study.
AB  - BACKGROUND AND PURPOSE: Lithuania is one of the countries with the highest
      incidence of tick-borne encephalitis (TBE) in Europe. The aim of this study was
      to describe the epidemiological patterns of TBE in Lithuania, and characterize
      clinical features in adults in the light of the high incidence in recent years.
      METHODS: Surveillance data available on the website of the Centre for
      Communicable Diseases and AIDS of Lithuania were used to describe the
      epidemiological patterns of TBE. The retrospective study included 712 patients
      hospitalized in the Centre for Infectious Diseases and the Centre for Neurology
      of Vilnius University in the years 2005-2014. RESULTS: Tick-borne encephalitis
      incidence rates have been increasing by 8.5% per year for the 45-year period from
      1970 to 2014. The joinpoint model finds two joinpoints at 1991 and 1994, with a
      significant decrease of 8.4% per year (P < 0.05) prior to the joinpoint at 1991,
      and a rise of 195.2% afterwards. TBE presented with meningoencephalitis in 556
      cases (81.3%). A total of 129 patients (18%) had a severe case of the disease.
      The most common neurological signs were ataxia (579, 81.3%), meningeal signs
      (474, 66.5%) and tremor (338, 47.5%). Limb paresis was observed in 6.3% of
      patients. Five patients (0.7%) died, and 544 patients (76.7%) were discharged
      with sequelae. CONCLUSIONS: Intensified efforts in promoting TBE vaccination will
      be needed in the light of the high incidence and expanded spatial distribution.
      Significant prognostic factors for severe cases of the disease were age above 61
      and delayed immune response of specific immunoglobulin G.

PMID- 29053889
TI  - Optimization of mass spectrometry acquisition parameters for determination of
      polycarbonate additives, degradation products, and colorants migrating from food
      contact materials to chocolate.
AB  - The interest towards "substances of emerging concerns" referred to objects
      intended to come into contact with food is recently growing. Such substances can
      be found in traces in simulants and in food products put in contact with plastic
      materials. In this context, it is important to set up analytical systems
      characterized by high sensitivity and to improve detection parameters to enhance
      signals. This work was aimed at optimizing a method based on UHPLC coupled to
      high resolution mass spectrometry to quantify the most common plastic additives,
      and able to detect the presence of polymers degradation products and coloring
      agents migrating from plastic re-usable containers. The optimization of mass
      spectrometric parameter settings for quantitative analysis of additives has been
      achieved by a chemometric approach, using a full factorial and d-optimal
      experimental designs, allowing to evaluate possible interactions between the
      investigated parameters. Results showed that the optimized method was
      characterized by improved features in terms of sensitivity respect to existing
      methods and was successfully applied to the analysis of a complex model food
      system such as chocolate put in contact with 14 polycarbonate tableware samples.
      A new procedure for sample pre-treatment was carried out and validated, showing
      high reliability. Results reported, for the first time, the presence of several
      molecules migrating to chocolate, in particular belonging to plastic additives,
      such Cyasorb UV5411, Tinuvin 234, Uvitex OB, and oligomers, whose amount was
      found to be correlated to age and degree of damage of the containers.

PMID- 29053890
TI  - Prospective comparison of acute motor axonal neuropathy and acute inflammatory
      demyelinating polyradiculoneuropathy in 140 children with Guillain-Barre syndrome
      in India.
AB  - INTRODUCTION: There have been few reports on subtypes of Guillain-Barre syndrome
      (GBS) in children. We compared clinical and laboratory findings of acute
      inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal
      neuropathy (AMAN). METHODS: One hundred forty children with GBS were included.
      Based on nerve conduction study (NCS) findings, patients were subclassified as
      AIDP, AMAN, acute motor sensory axonal neuropathy (AMSAN), and equivocal.
      RESULTS: Clinically, 72.1% of patients had pure motor, 24.3% motor sensory, and
      3.4% Miller Fisher syndrome. Based on NCS, 67.8% of patients had AIDP, 23.6% had
      AMAN, and 4.3% had AMSAN. By 3 months, 2.1% patients had died, 47.1% had complete
      recovery, and 24.3% had poor recovery (wheelchair-bound). Children with AMAN had
      more frequent lower limb weakness (P = 0.02) and a lower probability of complete
      recovery (P = 0.01) at 3 months than children with AIDP (56% vs. 30%).
      DISCUSSION: AIDP is the most common GBS subtype in children. It is characterized
      by better recovery at 3 months when compared with AMAN. Muscle Nerve 57: 761-765,
      2018.

PMID- 29053891
TI  - Look beyond the door, not through the keyhole: evidence from a cognitive
      assessment including social cognition evaluation in multiple sclerosis.

PMID- 29053893
TI  - Unilateral faciobrachial weakness: An unusual neuromuscular presentation Of West
      Nile Virus infection.

PMID- 29053892
TI  - Ultra-Fast Molecular Rotors within Porous Organic Cages.
AB  - Using variable temperature 2 H static NMR spectra and 13 C spin-lattice
      relaxation times (T1 ), we show that two different porous organic cages with
      tubular architectures are ultra-fast molecular rotors. The central para-phenylene
      rings that frame the "windows" to the cage voids display very rapid rotational
      rates of the order of 1.2-8*106  Hz at 230 K with low activation energy barriers
      in the 12-18 kJ mol-1 range. These cages act as hosts to iodine guest molecules,
      which dramatically slows down the rotational rates of the phenylene groups (5
      10*104  Hz at 230 K), demonstrating potential use in applications that require
      molecular capture and release.

PMID- 29053894
TI  - French translation and cross-cultural adaptation of The Myotonic Dystrophy Health
      Index.
AB  - INTRODUCTION: Validation studies of disease-specific instruments for myotonic
      dystrophy type-1 (DM1) are required prior to their global use in clinical trials
      involving different cultures and countries. Here we translate and culturally
      adapt the Myotonic Dystrophy Health Index (MDHI), a disease-specific patient
      reported outcome (PRO) measure, for a French DM1 population. METHODS: Using the
      International Society for Pharmacoeconomics and Outcomes Research Task Force
      method for translation and adaptation of PRO questionnaires, we created a French
      translation of the MDHI. We subsequently tested this instrument in a cohort of
      French-speaking patients with DM1. RESULTS: The MDHI was forward and back
      translated and modified by consensus to create the most compatible translation.
      Cognitive interviews were conducted with 5 patients with DM1 to ensure the
      usability and understanding of the translation. DISCUSSION: The French version of
      the MDHI is an optimal translation of the original instrument that is acceptable
      to native patients and ready for clinical trial use. Muscle Nerve 57: 686-689,
      2018.

PMID- 29053896
TI  - Quality and reporting of guidelines on the diagnosis and management of dystonia.
AB  - BACKGROUND AND PURPOSE: The quality of clinical practice guidelines on dystonia
      has not yet been assessed. Our aim was to appraise the methodological quality of
      guidelines worldwide and to analyze the consistency of their recommendations.
      METHODS: We searched for clinical practice guidelines on dystonia
      diagnosis/treatment in the National Guideline Clearinghouse, PubMed, National
      Institute for Health and Care Excellence, Guidelines International Network and
      Web of Science databases. We also searched for guidelines on homepages of
      international neurological societies. We asked for guidelines from every
      Management Committee member of the BM1101 Action of the Cooperation between
      Science and Technology European framework and every member of the International
      Parkinson and Movement Disorders Society with special interest in dystonia.
      RESULTS: Fifteen guidelines were evaluated. Among guidelines on treatment, only
      one from the American Academy of Neurology could be considered as high quality.
      Among guidelines on diagnosis and therapy, the guideline from the European
      Federation of Neurological Societies was recommended by the appraisers. Clinical
      applicability and reports of editorial independence were the greatest
      shortcomings. The rigor of development was poor and stakeholder involvement was
      also incomplete in most guidelines. Discrepancies among recommendations may
      result from the weight given to consensus statements and expert opinions due to
      the lack of evidence, as well as inaccuracy of disease classification.
      CONCLUSIONS: The quality of appraised guidelines was low. It is necessary to
      improve the quality of guidelines on dystonia, and the applied terminology of
      dystonia also needs to be standardized.

PMID- 29053897
TI  - Scientists Investigate the Application of Immunotherapy to Many Cancer Sites:
      Breast and prostate cancers prove more challenging, but progress is occurring.

PMID- 29053898
TI  - Chronic pain has a strong impact on quality of life in facioscapulohumeral
      muscular dystrophy.
AB  - INTRODUCTION: Earlier small case series and clinical observations reported on
      chronic pain playing an important role in facioscapulohumeral dystrophy (FSHD).
      The aim of this study was to determine the characteristics and impact of pain on
      quality of life (QoL) in patients with FSHD. METHODS: We analyzed patient
      reported outcome measures collected through the U.K. FSHD Patient Registry.
      RESULTS: Of 398 patients, 88.6% reported pain at the time of study. The most
      frequent locations were shoulders and lower back. A total of 203 participants
      reported chronic pain, 30.4% of them as severe. The overall disease impact on QoL
      was significantly higher in patients with early onset and long disease duration.
      Chronic pain had a negative impact on all Individualised Neuromuscular Quality of
      Life Questionnaire domains and overall disease score. DISCUSSION: Our study shows
      that pain in FSHD type 1 (FSHD1) is frequent and strongly impacts on QoL, similar
      to other chronic, painful disorders. Management of pain should be considered when
      treating FSHD1 patients. Muscle Nerve 57: 380-387, 2018.

PMID- 29053899
TI  - Peptidergic nerve fibers in the urethra: Morphological and neurochemical
      characteristics in female mice of reproductive age.
AB  - BACKGROUND: Peptidergic nerve fibers provide important contributions to urethral
      function. Urethral innervation of female mice is not well documented. AIMS: To
      determine the distribution and projection sites of nerve fibers immunoreactive
      for vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP),
      substance P (SP), and neuropeptide Y (NPY) in the urethra of wild-type control
      mice and compare innervation characteristics between the proximal and distal
      urethra of young nullipara and older multipara mice. Furthermore, to identify the
      location and neurochemical coding of the spinal afferent nerve endings in the
      urethra, whose sensory neurons reside in lumbosacral dorsal root ganglia (DRG).
      METHODS: Multiple labeling immunohistochemistry of urethral sections of
      nulliparous (6-8 weeks old), and multiparous (9-12 months old) mice, and
      anterograde axonal tracing from L5-S2 (DRG) in vivo. RESULTS: Abundant VIP-, CGRP
      , SP-, and NPY-immunoreactive nerve fibers were identified in the adventitia,
      muscularis, and lamina propria of proximal and distal segments of the urethra. A
      proportion of fibers were closely associated with blood vessels, glands, and
      cells immunoreactive for PGP9.5. The epithelium contained abundant nerve fibers
      immunoreactive for CGRP and/or SP. Epithelial innervation was increased in the
      distal urethra of multipara mice. Abundant fibers were traced from L5-S2 DRG to
      all urethral regions. CONCLUSIONS: We present the first identification of spinal
      afferent endings in the urethra. Peptidergic nerve fibers, including multiple
      populations of spinal afferents, provide rich innervation of the female mouse
      urethra. The morphology of fibers in the epithelium and other regions suggests
      multiple nerve-cell interactions impacting on urethral function.

PMID- 29053900
TI  - Hair coat properties of donkeys, mules and horses in a temperate climate.
AB  - BACKGROUND: There are clear differences between donkeys and horses in their
      evolutionary history, physiology, behaviour and husbandry needs. Donkeys are
      often kept in climates that they are not adapted to and as such may suffer
      impaired welfare unless protection from the elements is provided. OBJECTIVES: To
      compare some of the hair coat properties of donkeys, mules and horses living
      outside, throughout the year, in the temperate climate of the UK. STUDY DESIGN:
      Longitudinal study. METHODS: Hair samples were taken from 42 animals: 18 donkeys
      (4 females, 14 males), 16 horses (6 females, 10 males) and eight mules (5
      females, 3 males), in March, June, September and December. The weight, length and
      width of hair were measured, across the four seasons, as indicators of the hair
      coat insulation properties. RESULTS: Donkeys' hair coats do not significantly
      differ across the seasons. All three measurements of the insulation properties of
      the hair samples indicate that donkeys do not grow a winter coat and that their
      hair coat was significantly lighter, shorter and thinner than that of horses and
      mules in winter. In contrast, the hair coats of horses changed significantly
      between seasons, growing thicker in winter. MAIN LIMITATIONS: The measurements
      cover only a limited range of features that contribute to the thermoregulation of
      an animal. Further research is needed to assess shelter preferences by
      behavioural measures, and absolute heat loss via thermoimaging. CONCLUSIONS:
      Donkeys, and to a lesser extent mules, appear not to be as adapted to colder, wet
      climates as horses, and may therefore require additional protection from the
      elements, such as access to a wind and waterproof shelter, in order for their
      welfare needs to be met.

PMID- 29053901
TI  - Familial hypercholesterolaemia in patients with ischaemic stroke or transient
      ischaemic attack.
AB  - BACKGROUND AND PURPOSE: Identification of patients with familial
      hypercholesterolaemia (FH) is a prerequisite for the appropriate management of
      their excess cardiovascular risk. It is currently unknown how many patients with
      acute ischaemic stroke or transient ischaemic attack (TIA) are affected by FH and
      whether systematic screening for FH is warranted in these patients. METHODS: The
      prevalence of a clinical diagnosis of FH was estimated in a large representative
      series of patients with acute ischaemic stroke or TIA (ABCD2 score >= 3) using
      the Dutch Lipid Clinic Network Algorithm (DLCNA; possible FH >=3,
      probable/definite FH >=6). RESULTS: Out of 1054 patients included in the present
      analysis, 14 had probable/definite FH (1.3%; 95% confidence interval 0.6-2.0) and
      107 possible FH (10.2%; 8.4-12.0) corresponding to an overall prevalence of
      potential FH of 11.5%. Prevalences were even higher in patients with stroke/TIA
      manifestation before age 55 in men or 60 in women (3.1%, 0.6-5.6; and 13.1%, 8.3
      17.9) and those with a prior history of cardiovascular disease (2.6%, 0.9-4.3;
      and 15.1%, 11.3-18.9). Of note, in two-thirds of our patients with
      probable/definite and possible FH, stroke or TIA was the initial clinical disease
      manifestation. CONCLUSIONS: The frequency of potential FH, based on clinical
      criteria, in patients with acute ischaemic stroke or TIA was 11.5% and that of
      probable/definite FH (1.3%) was similar to recently reported counts for patients
      with acute coronary syndrome (1.6%). FH screening using the DLCNA is feasible in
      clinical routine and should be considered as part of the usual diagnostic work
      up.

PMID- 29053902
TI  - Sonographic evaluation of the vagus nerves: Protocol, reference values, and side
      to-side differences.
AB  - INTRODUCTION: Reported sonographic reference values for the vagus nerves (VNs)
      vary greatly. We aimed to generate reference values in a large cohort and examine
      intrarater, interrater, and across-ultrasound systems agreement. METHODS: The VNs
      of 60 healthy subjects were examined by 2 sonographers and with 2 ultrasound
      systems. Cross-sectional areas (CSAs) of each VN were assessed at the level of
      the carotid sinus [proximal measurement level (ML)] and thyroid gland (distal
      ML). RESULTS: Mean VN CSA was significantly larger on the right side (proximal
      ML: 2.7 +/- 0.6 mm2 vs. 2.1 +/- 0.5 mm2 ; distal ML: 2.6 +/- 0.6 mm2 vs. 1.9 +/-
      0.4 mm2 ). VN CSA decreased with increasing age. There were good intrarater,
      interrater, and across-ultrasound systems agreements. DISCUSSION: The right VN
      CSA is significantly larger than the left. These side- and age-specific reference
      values for the VN may be useful for future studies. Muscle Nerve 57: 766-771,
      2018.

PMID- 29053903
TI  - Galectin-3: an emerging biomarker in stroke and cerebrovascular diseases.
AB  - The carbohydrate-binding molecule galectin-3 has garnered significant attention
      recently as a biomarker for various conditions ranging from cardiac disease to
      obesity. Although there have been several recent studies investigating its role
      in stroke and other cerebrovascular diseases, awareness of this emerging
      biomarker in the wider neurology community is limited. We performed a systematic
      search in PubMed, Embase, Scopus, CINAHL, Clinicaltrials.gov and the Cochrane
      library in November and December 2016 for articles related to galectin-3 and
      cerebrovascular disease. We included both human and pre-clinical studies in order
      to provide a comprehensive view of the state of the literature on this topic. The
      majority of the relevant literature focuses on stroke, cerebral ischemia and
      atherosclerosis, but some recent attention has also been devoted to intracranial
      and subarachnoid hemorrhage. Higher blood levels of galectin-3 correlate with
      worse outcomes in atherosclerotic disease as well as in intracranial and
      subarachnoid hemorrhage in human studies. However, experimental evidence
      supporting the role of galectin-3 in these phenotypes is not as robust. It is
      likely that the role of galectin-3 in the inflammatory cascade within the central
      nervous system following injury is responsible for many of its effects, but its
      varied physiological functions and multiple sites of expression mean that it may
      have different effects depending on the nature of the disease condition and the
      time since injury. In summary, experimental and human research raises the
      possibility that galectin-3, which is closely linked to the inflammatory cascade,
      could be of value as a prognostic marker and therapeutic target in
      cerebrovascular disease.

PMID- 29053904
TI  - A direct aspiration first pass technique for acute stroke therapy: a systematic
      review and meta-analysis.
AB  - BACKGROUND AND PURPOSE: A direct aspiration first pass technique (ADAPT),
      involving the first-line use of a large-bore distal aspiration catheter, is a new
      strategy in the mechanical thrombectomy of acute ischemic stroke caused by large
      vessel occlusion. However, its impact on reperfusion rates, clinical outcomes and
      complication rates has not been fully examined. METHODS: We conducted a
      systematic review of the literature searching multiple databases for reports on
      thrombectomy of acute stroke with ADAPT and performed meta-analyses of clinical
      and radiographic outcomes. RESULTS: We selected 16 articles that included a total
      of 1378 patients treated with ADAPT. The mean admission National Institutes of
      Health Stroke Scale score was 17 and pre-treatment intravenous thrombolysis was
      used in 51% of cases. The successful recanalization (thrombolysis in cerebral
      ischemia 2b-3) rate was 66% [95% confidence interval (CI), 59-72%] with ADAPT and
      a rescue stent retriever was used in 31% of cases (95% CI, 24-37%) yielding an
      overall thrombolysis in cerebral ischemia 2b-3 rate of 89% (95% CI, 85-92%). We
      found a pooled estimate of 50% (95% CI, 45-54%) for functional independence
      (modified Rankin Scale score 0-2) at 90 days, 15% (95% CI, 10-21%) for mortality
      within 90 days and 5% (95% CI, 3-7%) for symptomatic intracranial hemorrhage.
      CONCLUSIONS: ADAPT therapy is associated with similar reperfusion rates, clinical
      outcomes and complication rates compared with thrombectomy with stent retrievers.
      However, the major limitations of current evidence (i.e. retrospective studies
      and selection bias) indicate a need for adequately powered, multicenter
      randomized controlled trials to determine the best strategy.

PMID- 29053905
TI  - Distinct predictive role of collateral status on clinical outcome in variant
      stroke subtypes of acute large arterial occlusion.
AB  - BACKGROUND AND PURPOSE: Clinical trials have shown that robust collateral flow
      has a relationship with good clinical outcome; however, different stroke subtypes
      were lumped together. This study explored the relationship between baseline
      collaterals and the onset-to-imaging time (OIT) and the correlation between pre
      treatment collateral status and clinical outcome amongst different subtypes.
      METHOD: Prospectively collected data from consecutive acute ischaemic stroke
      patients with acute middle cerebral artery occlusion who received reperfusion
      therapy were reviewed. The regional leptomeningeal score (20 points) was based on
      the scoring extent of contrast opacification in the six Alberta Stroke Program
      Early CT Score (ASPECTS) cortical regions (M1-6), parasagittal anterior cerebral
      artery territory and the basal ganglia by perfusion-derived dynamic four
      dimensional computed tomography angiography (4D CTA). Stroke subtype was
      determined by the TOAST classification criteria. A 3-months modified Rankin Scale
      score of 0-2 was defined as a good outcome. RESULTS: The analysis included 158
      patients: 30 (19.0%) patients had large artery atherosclerotic stroke (LAA), 87
      (55.1%) cardioembolic stroke (CE) and 41 (25.9%) stroke of undetermined etiology.
      Baseline collateral was negatively correlated with OIT (P = 0.0205) in the CE
      group after adjusting for female sex, smoking, hyperlipidemia, baseline National
      Institutes of Health Stroke Scale (NIHSS) and baseline mismatch ratio, but not in
      the LAA group. Baseline collateral showed a strong relationship with good
      clinical outcome after adjusting for recanalization, baseline NIHSS, age and
      female sex (odds ratio 1.120, confidence interval 1.013-1.238, P = 0.027) in all
      patients and in the CE group (odds ratio 3.223, confidence interval 1.212-8.570,
      P = 0.019), but not in the LAA patients. CONCLUSIONS: Based on 4D CTA, sustained
      good leptomeningeal collaterals may predict good outcome in CE but not in LAA
      patients. Moreover, the extent of collaterals was associated with OIT in the CE
      patients, which indicates prompt reperfusion therapy in this group of patients.

PMID- 29053906
TI  - Serum complement levels in anti-N-methyl-d-aspartate receptor encephalitis.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate the relationship between
      serum complement and anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis.
      METHODS: Serum complement (C3, C4 and CH50), immunoglobulins (IgG, IgM and IgA)
      and C-reactive protein (CRP) were evaluated in 40 patients with anti-NMDAR
      encephalitis and 40 controls. Follow-up evaluations of 11 of the 40 patients with
      anti-NMDAR encephalitis were conducted 6 months after admission. Modified Rankin
      Scale (mRS) scores and clinical and cerebrospinal fluid parameters were evaluated
      in patients with anti-NMDAR encephalitis. RESULTS: Serum C4 levels were
      significantly higher in patients with anti-NMDAR encephalitis than in controls (P
      = 0.003), especially in female patients (P = 0.001) and those with severe
      impairment (mRS >= 4; P < 0.001). Serum CH50 levels were significantly higher in
      patients with severe impairment (P = 0.007) and limited treatment responses (P =
      0.007). Serum C4 was associated with C3 (r = 0.506, P = 0.001), CH50 (r = 0.478,
      P = 0.002) and mRS score (r = 0.607, P < 0.001). Serum C3 was associated with
      CH50 (r = 0.339, P = 0.032) and cerebrospinal fluid white blood cells (r = 0.351,
      P = 0.026). Serum CH50 was associated with age, mRS score and CRP. Follow-up
      evaluations revealed that mRS scores were significantly lower than those before
      treatment, and a significant negative correlation was observed between the change
      in C3 levels and the change in mRS score. CONCLUSION: Our results demonstrated
      that serum C4 levels were elevated and associated with C3, CH50 and CRP levels,
      and disease severity in patients with anti-NMDAR encephalitis.

PMID- 29053907
TI  - Motor performance deterioration accelerates after 50 years of age in Charcot
      Marie-Tooth type 1A patients.
AB  - BACKGROUND AND PURPOSE: The aim of our study was to describe, by a case-control
      and cross-sectional design, the correlation between clinical impairment and age
      in Charcot-Marie-Tooth type 1A (CMT1A) patients. METHODS: Seventy CMT1A patients
      and 70 sex- and age-matched healthy controls were enrolled. Motor performance was
      assessed through the 10-m walk test, the 6-min walk test and the 9-hole peg test
      of the dominant and non-dominant side, and muscle strength was measured by using
      the Medical Research Council score. In the CMT1A group, disability and quality of
      life were evaluated using the Charcot-Marie-Tooth Neuropathy Score (CMTNS) and
      the Short Form 36 (SF-36) questionnaire. Cross-sectional relationships between
      age and all clinical measures were analyzed and differences in the slopes between
      cases and controls were calculated. The occurrence of a structural change in the
      age-related progression of clinical measures was explored. RESULTS: The
      deterioration of motor performance correlated with age in both groups with a
      greater slope in CMT1A patients than controls. The deterioration of CMTNS and SF
      36 correlated with age in the CMT1A group. The deterioration of all clinical
      measures with the exception of the SF-36 questionnaire showed a structural change
      at the 50th year of age. The rate of deterioration was no different between
      patients and controls until 50 years of age, whereupon it became significantly
      greater in CMT1A patients. CONCLUSION: Our study supports that the disease
      progression in CMT1A patients is an age-related process and the 50th year of age
      represents a critical moment after which the clinical decline becomes faster.

PMID- 29053908
TI  - No time to hesitate in acute in-hospital stroke!

PMID- 29053909
TI  - Impact of ledipasvir/sofosbuvir on the work productivity of genotype 1 chronic
      hepatitis C patients in Asia.
AB  - Chronic, untreated hepatitis C virus (HCV) infection is associated with a poor
      clinical prognosis and a detrimental impact on patients' lives, including on work
      productivity. To estimate the value of productivity losses due to genotype 1
      (GT1) HCV infection in Hong Kong, Singapore, South Korea and Taiwan and to
      estimate the potential productivity gains associated with treating patients with
      ledipasvir/sofosbuvir (LDV/SOF) therapy, an economic model was developed with a
      time horizon of 1 year. Hepatitis C virus patients entered the model at 12 weeks
      post-treatment, having achieved or not achieved sustained virological response
      (SVR). Absenteeism and presenteeism rates were taken from a pooled analysis of
      data from the ION 1-3 studies. These rates were converted into hours of lost
      productivity, multiplied by the average wage and applied to the total employed,
      adult GT1 population in each country. Results were compared assuming no
      treatment, and assuming all patients were treated with LDV/SOF. Total
      productivity losses due to untreated HCV were: $11.3 million, $17.1 m, $146.0 m
      and $349.1 m in Hong Kong, Singapore, South Korea and Taiwan. LDV/SOF treatment
      resulted in economic gains of $4.5 m, $6.8 m, $58.7 m and $138 m, respectively.
      These gains were due to reduced presenteeism. The results were sensitive to
      changes in the prevalence of HCV and the average wage. In conclusion,
      productivity losses due to untreated HCV infection represent a substantial
      economic burden. By instituting universal HCV treatment with LDV/SOF (or other
      therapies with high SVR rates), productivity gains can be achieved.

PMID- 29053910
TI  - A simplified protocol using rituximab and immunoglobulin for ABO-incompatible low
      titre living donor liver transplantation.
AB  - BACKGROUND & AIMS: No consensus has been reached regarding optimal treatment
      strategies for ABO-incompatible (ABO-I) living donor liver transplantation
      (LDLT). We introduce a simplified protocol using rituximab and intravenous
      immunoglobulin (IVIG). METHODS: Data were analysed on adult patients who
      underwent ABO-I LDLT of which protocol added rituximab (300 mg/m2 ) before
      surgery and IVIG (0.8 g/kg) on post-operative days 1 and 4 to the conventional
      immunosuppressive regimen used in ABO-compatible (ABO-C) LDLT, without
      plasmapheresis, splenectomy or graft local infusion. The outcomes were compared
      with those of ABO-C LDLT by 1:2 propensity score-matched analysis. RESULTS:
      Consecutive 43 ABO-I LDLT patients were identified between 2014 and 2016. Before
      desensitization, the median isoagglutinin titre was 1:8 (range, 1:2-1:64). The
      titre was reduced to 4 (range, 0-16) at the time of LDLT. None showed a rebound
      rise of isoagglutinin titres. No antibody-mediated rejection occurred. Biliary
      stricture was the most common complication with an incidence of 30.2%. A
      comparator group of 86 ABO-C LDLT patients were selected. There was no
      statistical difference in the overall complication rate including acute cellular
      rejection, biliary complications and infection between ABO-I and ABO-C groups.
      The 3-year cumulative patient survival rates in the ABO-I and ABO-C groups were
      82.4% and 85.9% respectively (P = .115). CONCLUSIONS: A simplified protocol using
      rituximab and IVIG for ABO-I LDLT was safe and effective in achieving sufficient
      desensitization and comparable outcomes in patients with the titre no higher than
      1:64.

PMID- 29053911
TI  - Investigating the minimal clinically important difference for SNOT-22 symptom
      domains in surgically managed chronic rhinosinusitis.
AB  - BACKGROUND: Prior work has described 5 domains within the 22-item Sino-Nasal
      Outcomes Test (SNOT-22) that allow for stratification of symptoms into similar
      clusters and that can be used to direct therapy. Although the outcomes of various
      interventions on these symptom domains have been reported, minimal clinically
      important difference (MCID) values have not been investigated, which has limited
      clinical interpretation of these results. METHODS: This study was designed as a
      secondary analysis of a prospective, multi-institutional, observational cohort. A
      total of 276 patients with medically refractory CRS who underwent surgical
      management were enrolled. Distribution-based methods (half-standard deviation,
      standard error of measurement, Cohen's d, and the minimum detectable change) were
      used to compute MCID values for both SNOT-22 total and domain scores. The Medical
      Outcomes Study Short Form 6D (SF-6D) health utility score was used to
      operationalize anchor-based associations using receiver-operating characteristic
      (ROC) curves. RESULTS: The mean MCID of several distribution-based methods for
      total SNOT-22 scores was 9.0, in agreement with previously published metrics.
      Average MCID values for the rhinologic, extranasal rhinologic, ear/facial,
      psychological, and sleep domain scores were 3.8, 2.4, 3.2, 3.9, and 2.9,
      respectively. Anchor-based approaches with the SF-6D did not have strong
      predictive accuracy across total SNOT-22 scores or domains (ROC areas under-the
      curve <= 0.71), indicating weak associations between improvement in SNOT-22
      scores and health utility as measured by the SF-6D. CONCLUSION: This estimation
      of MCID values for the SNOT-22 symptom domains allows for improved clinical
      interpretation of results from past, present, and future rhinologic outcomes
      research.

PMID- 29053912
TI  - Community-based screening of hepatitis C with a one-step RNA detection algorithm
      from dried-blood spots: Analysis of key populations in Barcelona, Spain.
AB  - Alternative strategies are required to enhance the diagnosis of silent hepatitis
      C virus (HCV) infections in key populations at risk. Among them, HCV prevalence
      and bio-behavioural data are scarce for HIV-negative men who have sex with men
      (MSM) and men and trans-women sex workers. We sought to describe and assess the
      potential benefits of a community-based one-step HCV screening and confirmatory
      strategy for these populations in Barcelona. The screening strategy based on a
      real-time RT-PCR assay for HCV-RNA detection in dried-blood spots (DBS) was
      validated and implemented in addition to an antibody point-of-care test in a
      community centre. HCV prevalence was assessed, and bio-behavioural data were
      collected. The molecular assay was precise, reproducible, sensitive and specific.
      Four HIV-negative MSM reported being currently infected (0.75% HCV self-reported
      prevalence). Implementation of DBS testing was easy, and acceptability was >95%,
      but no silent HCV case was diagnosed (N = 580). High-risk sexual practices and
      drug use for sex were reported frequently. HIV prevalence was 4.7% in MSM and 10%
      in sex workers. Self-reported prevalence of other STIs ranged from 11.3% to
      36.2%. In conclusion, HCV-RNA testing in DBS showed a good performance, but the
      assessed one-step strategy does not seem beneficial in this setting. Although no
      silent HCV infections were detected, the observed high-risk behaviours and
      prevalence of other STIs suggest that HCV spread should be periodically monitored
      among these populations in Barcelona by means of behavioural surveillance, rapid
      antibody testing and molecular confirmation in DBS.

PMID- 29053914
TI  - Transabdominal preperitoneal bilateral inguinal hernia repair according to
      Stoppa's principles - a video vignette.

PMID- 29053913
TI  - Morphological changes of the internal carotid artery: prevalence and
      characteristics. A clinical and ultrasonographic study in a series of 19 804
      patients over 25 years old.
AB  - BACKGROUND AND PURPOSE: Morphological changes of the internal carotid arteries
      (McICA) are frequently found during cervical ultrasound studies. However, the
      etiology of McICA remains controversial. During this study, the prevalence and
      demographic characteristics of McICA, such as kinking, coiling or looping
      identified by Doppler ultrasound, were analysed and its relationship with
      vascular risk factors and stroke was assessed. METHODS: A retrospective study was
      performed by analysing 19 804 patients who were subjected to cervical
      ultrasonographic study between January 2000 and June 2012. The data were
      statistically analysed with SPSS(r) 20 and a multivariate logistic regression was
      performed. Statistical significance was accepted for P < 0.05 and 95% confidence
      intervals (CIs) were used. RESULTS: Morphological changes of the internal carotid
      arteries were present in 2678 patients (13.5%) and were unilateral in 61.6% of
      these cases. Carotid kinking was found in 80% of the patients, coiling in 16% and
      looping in 1%. In multivariate analysis, the presence of McICA was related to
      older groups (1.04; 95% CI, 1.04-1.05; P < 0.01), female gender (1.78; 95% CI,
      1.64-1.94; P < 0.01), patients with hyperlipidemia (1.28; 95% CI, 1.17-1.40; P <
      0.01), carotid thickness (1.22; 95% CI, 1.13-1.33; P < 0.01) and cardiac or
      cardioembolic disease (1.11; 95% CI, 1.01-1.21; P = 0.02). The results of this
      study indicate that kinking in the carotid artery was associated with ipsilateral
      cerebral ischemic events (1.43; 95% CI, 1.040-1.958; P < 0.05). CONCLUSION:
      Morphological changes of the internal carotid arteries were associated with
      aging, female gender and patients with hyperlipidemia, hypertension, diabetes and
      heart disease. Kinking was associated with ipsilateral cerebral ischemia.

PMID- 29053916
TI  - In Situ Wrapping Si Nanoparticles with 2D Carbon Nanosheets as High-Areal
      Capacity Anode for Lithium-Ion Batteries.
AB  - Silicon (Si) has aroused great interest as the most attractive anode candidate
      for energy-dense lithium-ion batteries (LIBs) in the past decade because of its
      significantly high capacity and low discharge potential. However, the large
      volume change during cycling impedes its practical application, which is more
      serious in the case of high mass loading. Designing Si anode with high mass
      loading and high areal capacity by a simple, scalable, and environmentally
      friendly method is still a big challenge. Herein, we report in situ one-pot
      synthesis of Si/C composite, where Si nanoparticles are wrapped by graphene-like
      2D carbon nanosheets. After 500 cycles at 420 mA g-1, the Si/C anode displays a
      gravimetric capacity of 881 mAh g-1 with 86.4% capacity being retained. More
      specially, a high areal capacity of 3.13 mAh cm-2 at 5.00 mg cm-2 after 100
      cycles is achieved. This study demonstrates a novel route for the preparation of
      the Si/C composite with high material utilization and may expand the possibility
      of future design Si-based anode with high areal capacity for high energy LIBs.

PMID- 29053917
TI  - Novel Bioconjugation Strategy Using Elevated Hydrostatic Pressure: A Case Study
      for the Site-Specific Attachment of Polyethylene Glycol (PEGylation) of
      Recombinant Human Ciliary Neurotrophic Factor.
AB  - In this paper, we reported a novel strategy for the site-specific attachment of
      polyethylene glycol (PEGylation) of proteins using elevated hydrostatic pressure.
      The process was similar to the conventional one except the reactor was under
      elevated hydrostatic pressure. The model protein was recombinant human ciliary
      neurotrophic factor (rhCNTF), and the reagent was monomethoxy-polyethylene glycol
      maleimide (mPEG-MAL). PEGylation with mPEG (40 kDa)-MAL at pH 7.0 under normal
      pressure for 5 h achieved a less than 5% yield. In comparison, when the pressure
      was elevated, the PEGylation yield was increased dramatically, reaching nearly
      90% at 250 MPa. Furthermore, the following phenomena were observed: (1) high
      hydrostatic-pressure PEGylation (HHPP) could operate at a low reactant ratio of
      1:1.2 (rhCNTF to mPEG-MAL), while the conventional process needs a much-higher
      ratio. (2) Short and long chains of PEG gave a similar yield of 90% in HHPP,
      while the conventional yield for the short chain of the PEG was higher than that
      of the long chain. (3) The reaction pH in the range of 7.0 to 8.0 had almost no
      influence upon the yield of HHPP, while the PEGylation yield was significantly
      increased by a factor of three from pH 7.0 to 8.0 at normal pressure. Surface
      accessibility analysis was performed using GRASP2 software, and we found that
      Cys17 of rhCNTF was located at the concave patches, which may have steric
      hindrance for the PEG to approach. The speculated benefit of HHPP was the
      facilitation of target-site exposure, reducing the steric hindrance and making
      the reaction much easier. Structure and activity analysis demonstrated that the
      HHPP product was comparable to the PEGylated rhCNTF prepared through a
      conventional method. Overall, this work demonstrated that HHPP, as we proposed,
      may have application potentials in various conjugations of biomacromolecules.

PMID- 29053919
TI  - Tuning the Two-Dimensional Electron Liquid at Oxide Interfaces by Buffer-Layer
      Engineered Redox Reactions.
AB  - Polar discontinuities and redox reactions provide alternative paths to create two
      dimensional electron liquids (2DELs) at oxide interfaces. Herein, we report high
      mobility 2DELs at interfaces involving SrTiO3 (STO) achieved using polar
      La7/8Sr1/8MnO3 (LSMO) buffer layers to manipulate both polarities and redox
      reactions from disordered overlayers grown at room temperature. Using resonant X
      ray reflectometry experiments, we quantify redox reactions from oxide overlayers
      on STO as well as polarity induced electronic reconstruction at epitaxial
      LSMO/STO interfaces. The analysis reveals how these effects can be combined in a
      STO/LSMO/disordered film trilayer system to yield high mobility modulation doped
      2DELs, where the buffer layer undergoes a partial transformation from perovskite
      to brownmillerite structure. This uncovered interplay between polar
      discontinuities and redox reactions via buffer layers provides a new approach for
      the design of functional oxide interfaces.

PMID- 29053920
TI  - Turn-on Fluorene Push-Pull Probes with High Brightness and Photostability for
      Visualizing Lipid Order in Biomembranes.
AB  - The rational design of environmentally sensitive dyes with superior properties is
      critical for elucidating the fundamental biological processes and understanding
      the biophysical behavior of cell membranes. In this study, a novel group of
      fluorene-based push-pull probes was developed for imaging membrane lipids. The
      design of these fluorogenic conjugates is based on a propioloyl linker to
      preserve the required spectroscopic features of the core dye. This versatile
      linker allowed the introduction of a polar deoxyribosyl head, a lipophilic chain,
      and an amphiphilic/anchoring group to tune the cell membrane binding and
      internalization. It was found that the deoxyribosyl head favored cell
      internalization and staining of intracellular membranes, whereas an amphiphilic
      anchor group ensured specific plasma membrane staining. The optimized fluorene
      probes presented a set of improvements as compared to commonly used
      environmentally sensitive membrane probe Laurdan such as red-shifted absorption
      matching the 405 nm diode laser excitation, a blue-green emission range
      complementary to the red fluorescent proteins, enhanced brightness and
      photostability, as well as preserved sensitivity to lipid order, as shown in
      model membranes and living cells.

PMID- 29053918
TI  - Active Site Interactions Impact Phosphoryl Transfer during Replication of Damaged
      and Undamaged DNA by Escherichia coli DNA Polymerase I.
AB  - Replicative DNA polymerases are able to discriminate between very similar
      substrates with high accuracy. One mechanism by which E. coli DNA polymerase I
      checks for Watson-Crick geometry is through a hydrogen bonding fork between
      Arg668 and the incoming dNTP and the minor groove of the primer terminus. The
      importance of the Arg-fork was examined by disrupting it with either a guanine to
      3-deazaguanine substitution at the primer terminus or the use of a carbocyclic
      deoxyribose analog of dUTP. Using thio-substituted dNTPs and differential quench
      techniques, we determined that when the Arg-fork was disrupted, the rate-limiting
      step changed from a conformational change to phosphodiester bond formation. This
      result indicates that Arg668 is involved in the phosphoryl transfer step. We
      examined the role of the Arg-fork in the replication of four DNA damaged
      templates, O6-methylguanine (O6-mG), 8-oxo-7,8-dihydroguanine (oxoG), O2-[4-(3
      pyridyl)-4-oxobutyl]thymine (O2-POB-T), and N2-[(7S,8R,9S,10R)-7,8,9,10
      tetrahydro-8,9,10-trihydroxybenzo[a]pyren-7-yl]-guanine (N2-BP-G). In general,
      the guanine to 3-deazaguanine substitution caused a decrease in kpol that was
      proportional to kpol over five orders of magnitude. The linear relationship
      indicates that the Arg668-fork helps catalyze phosphoryl transfer by the same
      mechanism with all the substrates. Exceptions to the linear relationship were the
      incorporations of dTTP opposite G, oxoG, and O6mG, which showed large decreases
      in kpol, similar to that exhibited by the Watson-Crick base pairs. It was
      proposed that the incorporation of dTTP opposite G, oxoG, and O6mG occurred via
      Watson-Crick-like structures.

PMID- 29053922
TI  - Progress in Top-Down Control of Bottom-Up Assembly.

PMID- 29053921
TI  - Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant
      Rejection.
AB  - Kidney transplant patients require life-long surveillance to detect allograft
      rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive
      procedure with the risk of complications and comparatively high cost. Conversely,
      serum creatinine or urinary proteins are noninvasive alternatives but are late
      markers with low specificity. We report a urine-based platform to detect kidney
      transplant rejection. Termed iKEA (integrated kidney exosome analysis), the
      approach detects extracellular vesicles (EVs) released by immune cells into
      urine; we reasoned that T cells, attacking kidney allografts, would shed EVs,
      which in turn can be used as a surrogate marker for inflammation. We optimized
      iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When
      applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs
      in kidney rejection patients and achieved high detection accuracy (91.1%). Fast,
      noninvasive, and cost-effective, iKEA could offer new opportunities in managing
      transplant recipients, perhaps even in a home setting.

PMID- 29053923
TI  - Loss and Reformation of Ruthenium Alkylidene: Connecting Olefin Metathesis,
      Catalyst Deactivation, Regeneration, and Isomerization.
AB  - Ruthenium-based olefin metathesis catalysts are used in laboratory-scale organic
      synthesis across chemistry, largely thanks to their ease of handling and
      functional group tolerance. In spite of this robustness, these catalysts readily
      decompose, via little-understood pathways, to species that promote double-bond
      migration (isomerization) in both the 1-alkene reagents and the internal-alkene
      products. We have studied, using density functional theory (DFT), the reactivity
      of the Hoveyda-Grubbs second-generation catalyst 2 with allylbenzene, and
      discovered a facile new decomposition pathway. In this pathway, the alkylidene
      ligand is lost, via ring expansion of the metallacyclobutane intermediate,
      leading to the spin-triplet 12-electron complex (SIMes)RuCl2 (3R21, SIMes = 1,3
      bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene). DFT calculations
      predict 3R21 to be a very active alkene isomerization initiator, either operating
      as a catalyst itself, via a eta3-allyl mechanism, or, after spin inversion to
      give R21 and formation of a cyclometalated Ru-hydride complex, via a hydride
      mechanism. The calculations also suggest that the alkylidene-free ruthenium
      complexes may regenerate alkylidene via dinuclear ruthenium activation of alkene.
      The predicted capacity to initiate isomerization is confirmed in catalytic tests
      using p-cymene-stabilized R21 (5), which promotes isomerization in particular
      under conditions favoring dissociation of p-cymene and disfavoring formation of
      aggregates of 5. The same qualitative trends in the relative metathesis and
      isomerization selectivities are observed in identical tests of 2, indicating that
      5 and 2 share the same catalytic cycles for both metathesis and isomerization,
      consistent with the calculated reaction network covering metathesis, alkylidene
      loss, isomerization, and alkylidene regeneration.

PMID- 29053924
TI  - Reply: A New Direction: Sleep and Neuropsychological Impairment after Critical
      Illness.

PMID- 29053925
TI  - Mesenchymal Stem Cell Secretome Improves Tendon Cell Viability In Vitro and
      Tendon-Bone Healing In Vivo When a Tissue Engineering Strategy Is Used in a Rat
      Model of Chronic Massive Rotator Cuff Tear.
AB  - BACKGROUND: Massive rotator cuff tears (MRCTs) represent a major clinical
      concern, especially when degeneration and chronicity are involved, which highly
      compromise healing capacity. PURPOSE: To study the effect of the secretome of
      mesenchymal stem cells (MSCs) on tendon cells (TCs) followed by the combination
      of these activated TCs with an electrospun keratin-based scaffold to develop a
      tissue engineering strategy to improve tendon-bone interface (TBi) healing in a
      chronic MRCT rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human
      TCs (hTCs) cultured with the human MSCs (hMSCs) secretome (as conditioned media
      [CM]) were combined with keratin electrospun scaffolds and further implanted in a
      chronic MRCT rat model. Wistar-Han rats (N = 15) were randomly assigned to 1 of 3
      groups: untreated lesion (MRCT group, n = 5), lesion treated with a scaffold only
      (scaffold-only group, n = 5), and lesion treated with a scaffold seeded with hTCs
      preconditioned with hMSCs-CM (STC_hMSC_CM group, n = 5). After sacrifice, 16
      weeks after surgery, the rotator cuff TBi was harvested for histological analysis
      and biomechanical testing. RESULTS: The hMSCs secretome increased hTCs viability
      and density in vitro. In vivo, a significant improvement of the tendon maturing
      score was observed in the STC_hMSC_CM group (mean +/- standard error of the mean,
      15.6 +/- 1.08) compared with the MRCT group (11.0 +/- 1.38; P < .05).
      Biomechanical tests revealed a significant increase in the total elongation to
      rupture (STC_hMSC_CM, 11.99 +/- 3.30 mm; scaffold-only, 9.89 +/- 3.47 mm; MRCT,
      5.86 +/- 3.16 mm; P < .05) as well as a lower stiffness (STC_hMSC_CM, 6.25 +/-
      1.74 N/mm; scaffold-only, 6.72 +/- 1.28 N/mm; MRCT, 11.54 +/- 2.99 N/mm; P <
      .01). CONCLUSION: The results demonstrated that hMSCs-CM increased hTCs viability
      and density in vitro. Clear benefits also were observed when these primed cells
      were integrated into a tissue engineering strategy with an electrospun keratin
      scaffold, as evidenced by improved histological and biomechanical properties for
      the STC_hMSC_CM group compared with the MRCT group. CLINICAL RELEVANCE: This work
      supports further investigation into the use of MSC secretome for priming TCs
      toward a more differentiated phenotype, and it promotes the tissue engineering
      strategy as a promising modality to help improve treatment outcomes for chronic
      MRCTs.

PMID- 29053926
TI  - Comments on "Stressing the Brain...Acute Respiratory Distress Syndrome".

PMID- 29053928
TI  - Heat stress risk profiles for three non-woven coveralls.
AB  - The ACGIH(r) Threshold Limit Value(r) (TLV(r)) is used to limit heat stress
      exposures so that most workers can maintain thermal equilibrium. That is, the TLV
      was set to an upper limit of Sustainable exposures for most people. This article
      addresses the ability of the TLV to differentiate between Sustainable and
      Unsustainable heat exposures for four clothing ensembles over a range of
      environmental factors and metabolic rates (M). The four clothing ensembles (woven
      clothing, and particle barrier, water barrier and vapor barrier coveralls)
      represented a wide range of evaporative resistances. Two progressive heat stress
      studies provided data on 480 trials with 1440 pairs of Sustainable and
      Unsustainable exposures for the clothing over three levels of relative humidity
      (rh) (20, 50 and 70%), three levels of metabolic rate (115, 180, and 254 Wm-2)
      using 29 participants. The exposure metric was the difference between the
      observed wet bulb globe temperature (WBGT) and the TLV. Risk was characterized by
      odds ratios (ORs), Receiver Operating Characteristic (ROC) curves, and dose
      response curves for the four ensembles. Conditional logistic regression models
      provided information on ORs. Logistic regressions were used to determine ROC
      curves with area under the curve (AUC), model the dose-response curve, and
      estimate offsets from woven clothing. The ORs were about 2.5 per 1 degrees C-WBGT
      for woven clothing, particle barrier, and water barrier and for vapor barrier at
      50% rh. When using the published Clothing Adjustment Values (CAVs, also known as
      Clothing Adjustment Factors, CAFs) or the offsets that included different values
      for vapor barrier based on rh, the AUC for all clothing was 0.86. When the fixed
      CAVs of the TLV were used, the AUC was 0.81. In conclusion, (1) ORs and the
      shapes of the dose-response curves for the nonwoven coveralls were similar to
      woven clothing, and (2) CAVs provided a robust way to account for the risk of
      nonwoven clothing. The robust nature of CAV extended to the exclusion of
      different adjustments for vapor barrier by rh.

PMID- 29053927
TI  - Safety of pharmacotherapy options for bulimia nervosa and binge eating disorder.
AB  - INTRODUCTION: Eating disorders represent a set of psychiatric illnesses with
      lifelong complications and high relapse rates. Individuals with eating disorders
      are often stigmatized and clinicians have a limited set of treatments options.
      Pharmacotherapy has the potential to improve long term compliance and patient
      commitment to treatment for eating disorders. Areas covered: This review will
      examine the efficacy and safety profile of the FDA-approved medications for the
      treatment of bulimia nervosa (BN) and binge eating disorder (BED). This will
      include the evaluation of fluoxetine for BN, and lisdexamfetamine for BED. Safety
      information will be review from randomized control trials (RCT), open label
      trials, and case reports. Expert opinion: Fluoxetine for BN and lisdexamfetamine
      for BED are relatively safe and well-tolerated. Despite these properties, these
      two medications represent a limited arsenal for the pharmacological treatment of
      eating disorders. Thus, more research-based strategies are needed to develop
      safe, effective, and more targeted therapies for eating disorders.

PMID- 29053929
TI  - Characterizing workforces exposed to current and emerging non-carbonaceous
      nanomaterials in the U.S.
AB  - OBJECTIVE: Toxicology studies suggest that exposure to certain types of
      engineered nanomaterials (ENMs) may cause adverse health effects, but little is
      known about the workforce in the United States that produces or uses these
      materials. In addition, occupational exposure control strategies in this industry
      are not well characterized. This study identified U.S. ENM manufacturers and
      users (other than carbon nanotubes and nanofibers, which have been characterized
      elsewhere), determined workforce size, characterized types and quantities of
      materials used, occupational exposure control strategies, and the feasibility of
      occupational ENM exposure studies. METHODS: Eligible companies were identified
      and information was collected through phone surveys on nanomaterials produced or
      used, workforce size, location, work practices, and exposure control strategies.
      The companies were classified into groups for additional examinations. RESULTS:
      Forty-nine companies producing or using ENMs in the U.S. were identified. These
      companies employed at least 1,500 workers. Most companies produced or used some
      form of nanoscale metal. More than half of the eligible companies were suppliers
      for the coatings, composite materials, or general industries. Each company
      provided information about worker exposure reduction strategies through
      engineering controls, administrative controls, or personal protective equipment.
      Production-scale companies reported greater use of specific exposure control
      strategies for ENMs than laboratory-scale companies. CONCLUSIONS: Workplaces
      producing or using ENMs report using engineering and administrative controls as
      well as personal protective equipment to control worker exposure. Industrywide
      exposure assessment studies appear feasible due to workforce size. However, more
      effort must be taken to target industries using specific ENMs based on known
      toxicological effects and health risks.

PMID- 29053930
TI  - Social dimension and complexity differentially influence brain responses during
      feedback processing.
AB  - Recent research emphasizes the importance of social factors during performance
      monitoring. Thus, the current study investigated the impact of social stimuli 
      such as communicative gestures- on feedback processing. Moreover, it addressed a
      shortcoming of previous studies, which failed to consider stimulus complexity as
      potential confounding factor. Twenty-four volunteers performed a time estimation
      task while their electroencephalogram was recorded. Either social complex, social
      non-complex, non-social complex, or non-social non-complex stimuli were used to
      provide performance feedback. No effects of social dimension or complexity were
      found for task performance. In contrast, Feedback-Related Negativity (FRN) and
      P300 amplitudes were sensitive to both factors, with larger FRN and P300
      amplitudes after social compared to non-social stimuli, and larger FRN amplitudes
      after complex positive than non-complex positive stimuli. P2 amplitudes were
      solely sensitive to feedback valence and social dimension. Subjectively, social
      complex stimuli were rated as more motivating than non-social complex ones.
      Independently of each other, social dimension and visual complexity influenced
      amplitude variation during performance monitoring. Social stimuli seem to be
      perceived as more salient, which is corroborated by P2, FRN and P300 results, as
      well as by subjective ratings. This could be explained due to their given
      relevance during every day social interactions.

PMID- 29053931
TI  - Removal of Cu(II) in water by polymer enhanced ultrafiltration: Influence of
      polymer nature and pH.
AB  - This study presents an efficient removal of Cu(II) in water using the polymer
      enhanced ultrafiltration (PEUF) method. Polymer of different molecular weight
      (MW) (polyethyleneimine (PEI), sodium lignosulfonates (SLS) and dextrans) were
      investigated to evaluate efficiency in removal of Cu(II) in water by the PEUF
      method. The decomposition of Cu(II)-polymer complex was also evaluated in order
      to reuse polymers. Cu(II) complexation depends on the MW of chelating polymer and
      the pH of feed solution. It was found that the Cu(II) rejection increased with
      the polymer dosage with high removal of Cu(II) when using PEI and SLS at a 10:20
      (mg/mg) ratio ([Cu(II)]:[polymer]). It was found that the maximum chelating
      capacity was 15 mg of Cu(II) per 20 mg of PEI. The Cu(II)-PEI complex could be
      decomposed by acid addition and the polymer could be efficiently reused with
      multiple complexation-decomplexation cycles. A conceptual flow chart of the
      integrated process of efficient removal of Cu(II) by PEUF method is suggested.

PMID- 29053932
TI  - The patterns of in vitro cell-death and inflammatory cytokines induced by
      distinct BCG vaccine strains are differentially induced in human mononuclear
      cells.
AB  - Tuberculosis (TB) remains among the world's leading cause of mortality. For its
      control, studies of TB vaccines are needed. Since live-attenuated Mycobacterium
      bovis bacillus Calmette-Guerin (BCG) is the only TB vaccine currently in use,
      studies on the protective role of BCG are required. In this study, we analyzed
      host cells purified directly from whole blood of human immunodeficiency virus
      (HIV)-negative volunteers, comprising adult healthy donors (HD) and neonates
      (umbilical cord bloods, UCB), with the aim to directly compare in vitro immune
      responses with distinct BCG strains in human mononuclear cells. The Moreau,
      Pasteur, and Danish BCG strains were used to infect mononuclear cells in vitro
      for 48 h; bacilli viability and cell-death were subsequently detected by flow
      cytometry. In addition, cell culture supernatants were used in cytokine detection
      assays. Overall, the Moreau BCG strain induced higher levels of apoptosis than
      the Pasteur and Danish BCG strains in both the HD and UCB groups (p-value <
      0.05), and a human monocytic cell-line mirrored those cell-death patterns after
      BCG infection. The Moreau BCG strain, exclusively, induced Th1 cytokines at the
      highest levels in cells from adults (p-value < 0.05) when compared with both
      Pasteur and Danish BCG strains, whereas TGF-beta1 levels were reduced
      significantly (p-value < 0.01) in the HD group when cells were infected with the
      Moreau BCG vaccine. As expected, eight out of 22 pro-inflammatory cytokines were
      secreted at significant levels (p-value < 0.05) above the baseline rates in all
      BCG-infected cell cultures, in the HD group only. When analyzing these results,
      we excluded confounding factors related to storage and viability of the BCG
      strains used. These findings suggest that Moreau BCG is a more potent
      immunostimulating agent than the Pasteur and Danish BCG strains. Clinical trials
      will be needed to confirm these findings.

PMID- 29053933
TI  - Chronic administration of ellagic acid improved the cognition in middle-aged
      overweight men.
AB  - This study aimed to investigate if ellagic acid has beneficial effects on
      cognitive deficits in middle-aged overweight individuals and to propose a
      possible mechanism. A total of 150 middle-aged male participants, including 76
      normal-weight and 74 overweight men, aged between 45 to 55 years, were recruited
      for this study. Both normal-weight and overweight participants were administered
      either 50 mg ellagic acid or placebo cellulose daily for 12 weeks. Blood lipids,
      peripheral brain-derived neurotrophic factor (BDNF), and saliva cortisol were
      assessed on the last day of the procedure to investigate the effects induced by
      ellagic acid. The results revealed that ellagic acid treatment improved the
      levels of blood lipid metabolism with a 4.7% decline in total cholesterol, 7.3%
      decline in triglycerides, 26.5% increase in high-density lipoprotein, and 6.5%
      decline in low-density lipoprotein. Additionally, ellagic acid increased plasma
      BDNF by 21.2% in the overweight group and showed no effects on normal-weight
      participants. Moreover, the increased saliva cortisol level in overweight
      individuals was inhibited by 22.7% in a 12-week ellagic acid treatment. Also,
      compared with placebo, overweight individuals who consumed ellagic acid showed
      enhanced cognitive function as measured by the Wechsler Adult Intelligence Scale
      Revised and the Montreal Cognitive Assessment. To the best of our knowledge, this
      is the first report showing that ellagic acid prevents cognitive deficits through
      normalization of lipid metabolism, increase in plasma BDNF level, and reduction
      of saliva cortisol concentration. These results indicate that ellagic acid has a
      potential to restore cognitive performance related to mild age-related declines.

PMID- 29053934
TI  - Quantification of mold contamination in multi-level buildings using the
      Environmental Relative Moldiness Index.
AB  - The goal of this study was to evaluate the possible use of the Environmental
      Relative Moldiness Index (ERMI) to quantify mold contamination in multi-level,
      office buildings. Settled-dust samples were collected in multi-level, office
      buildings and the ERMI value for each sample determined. In the first study, a
      comparison was made between two identical four-story buildings. There were health
      complaints in one building but none in the other building. In the second study,
      mold contamination was evaluated on levels 6-19 of an office building with a
      history of water problems and health complaints. In the first study, the average
      ERMI value in the building with health complaints was 5.33 which was
      significantly greater than the average ERMI value, 0.55, in the non-complaint
      building. In the second study, the average ERMI values ranged from a low of -0.58
      on level 8 to a high of 5.66 on level 17, one of the top five ranked levels for
      medical symptoms or medication use. The mold populations of ten (six Group 1 and
      four Group 2) of the 36-ERMI molds were in significantly greater concentrations
      in the higher compared to lower ERMI environments. The ERMI metric may be useful
      in the quantification of water-damage and mold growth in multi-level buildings.

PMID- 29053936
TI  - Evaluation of an improved prototype mini-baghouse to control the release of
      respirable crystalline silica from sand movers.
AB  - The OSHA final rule on respirable crystalline silica (RCS) will require hydraulic
      fracturing companies to implement engineering controls to limit workers' exposure
      to RCS. RCS is generated by pneumatic transfer of quartz-containing sand during
      hydraulic fracturing operations. Chronic inhalation of RCS can lead to serious
      disease, including silicosis and lung cancer. NIOSH research identified at least
      seven sources where RCS aerosols were generated at hydraulic fracturing sites.
      NIOSH researchers developed an engineering control to address one of the largest
      sources of RCS aerosol generation, RCS escaping from thief hatches on the top of
      sand movers. The control, the NIOSH Mini-Baghouse Retrofit Assembly (NMBRA),
      mounts on the thief hatches. Unlike most commercially available engineering
      controls, the NMBRA has no moving parts and requires no power source. This
      article details the results of an evaluation of generation 3 of the NMBRA at a
      sand mine in Arkansas from May 19-21, 2015. During the evaluation, 168 area air
      samples were collected at 12 locations on and around a sand mover with and
      without the NMBRA installed. Analytical results for respirable dust and RCS
      indicated the use of the NMBRA effectively reduced concentrations of both
      respirable dust and RCS downwind of the thief hatches. Reductions of airborne
      respirable dust were estimated at 99+%; reductions in airborne RCS ranged from 98
      99%. Analysis of bulk samples of the dust showed the likely presence of freshly
      fractured quartz, a particularly hazardous form of RCS. Use of an improved filter
      fabric and a larger area of filter cloth led to substantial improvements in
      filtration and pressures during these trials, as compared to the generation 2
      NMBRA. Planned future design enhancements, including a weather cover, will
      increase the performance and durability of the NMBRA. Future trials are planned
      to evaluate the long-term operability of the technology.

PMID- 29053935
TI  - Capsaicin, the pungent principle of peppers, ameliorates alcohol-induced acute
      liver injury in mice via modulation of matrix metalloproteinases.
AB  - Alcohol, the most common cause for hepatic injury, may further deteriorate the
      hepatic tissue when left unattended. Capsaicin, the pungent principle of chilli
      peppers, possesses antioxidant and anti-inflammatory properties and is a proven
      dietary antioxidant in various ailments. However, its role in alcohol-induced
      hepatic injury is unclear. In this study, we investigated the effects of
      capsaicin on the hepatic tissue of mice treated with alcohol. Acute liver injury
      was induced in mice by oral gavage of 5 doses of 10 mL/kg of 50% ethyl alcohol at
      an interval of 12 h. The tissue antioxidant levels along with the mitochondrial
      functional parameters and matrix metalloproteinase levels were evaluated in the
      hepatic tissues of mice following alcohol challenge. The results showed that
      alcohol intake significantly attenuated the hepatic antioxidant levels and
      mitochondrial function. These changes were accompanied by enhanced serum hepatic
      injury markers and matrix metalloproteinases. However, capsaicin treatment (10
      and 20 mg/kg, oral) throughout the experimental period caused a drastic
      improvement in the hepatic tissue of the alcohol-treated mice, reflected by the
      normalization of hepatic enzyme and protein levels along with restored
      histological alterations. These results indicate that capsaicin, as a dietary
      intervention, may prevent alcohol-induced acute liver injury.

PMID- 29053937
TI  - Studies with herpes zoster vaccines in immune compromised patients.
AB  - INTRODUCTION: The active component of the herpes zoster vaccine (ZVL), licensed
      for people >=50 years of age, is a live attenuated varicella-zoster virus. ZVL is
      contraindicated for immune compromised individuals, with limited regard to the
      degree of immunosuppression. Areas covered: This review evaluates phase I and II
      and observational studies for ZVL, and published reports of the off-label use of
      ZVL, for conditions and therapies for which investigators considered the risk
      benefit for using ZVL to be favorable. It also discusses exploratory trials of
      ZVL for additional immune compromising conditions, and summarizes clinical
      guidelines from many countries and professional societies that are based upon
      recent investigations. Studies in immune compromised patients of investigational
      vaccines that do not contain live virus are reviewed. Expert commentary: It is
      likely that past and ongoing research with ZVL will define immune compromising
      diseases and/or therapies for which the risk-benefit for using ZVL vaccine is
      favorable. The main variables to consider in this assessment in immune
      compromised patients are safety, immunogenicity, protection against herpes
      zoster, and persistence of protection. Vaccination against herpes zoster prior to
      suppressing immunity is an important clinical strategy, although efficacy of this
      approach has not been evaluated in a clinical trial.

PMID- 29053938
TI  - Development of a nanogel-based nasal vaccine as a novel antigen delivery system.
AB  - INTRODUCTION: Nasal vaccination is one of the most effective immunization methods
      because it can induce effective antigen-specific immune responses not only at the
      mucosal site of administration but also at distant mucosal surfaces, as well as
      in the systemic compartment. Based on this advantage, many nasal vaccines are
      being developed and some have been licensed and marketed for clinical use.
      However, some have been withdrawn because of unacceptable adverse events such as
      inactivated influenza vaccine administrated with a heat-labile enterotoxin of
      Escherichia coli as an adjuvant. Thus, it is important to consider both the
      efficacy and safety of nasal vaccines. Areas covered: This review describes the
      benefits of cholesteryl group-bearing pullulan (CHP) nanogels for nasal vaccine
      delivery and vaccine development identified on Pubmed database with the term
      'Nanogel-based nasal vaccine'. Expert commentary: CHP nanogels have been
      developed as novel drug delivery system, and a cationic CHP nanogels have been
      demonstrated to induce effective immunity as a nasal vaccine antigen carrier.
      Since vaccine antigens incorporated into CHP nanogels have exhibited no brain
      deposition after nasal administration in mice and nonhuman primates, the vaccine
      seems safe, and could be a promising new delivery system.

PMID- 29053939
TI  - A conceptual model for take-home workplace exposures.
AB  - The boundary between occupational and environmental exposures is often
      artificial, as occupational hazards can readily escape the workplace. One way
      that this occurs is when workers "take-home" occupational hazards, exposing
      family members. While take-home exposures have long been recognized, there is no
      comprehensive framework describing the pathways by which workers bring home
      workplace hazards. In this article, we provide such a conceptual model that
      includes three pathways for take-home exposures: external contamination, internal
      dose, and behavior change of workers. This conceptual model should help to
      describe the problems of take-home exposures more comprehensively in future
      research.

PMID- 29053940
TI  - Reply: Comments on "Stressing the Brain...Acute Respiratory Distress Syndrome".

PMID- 29053941
TI  - A point-source outbreak of Coccidioidomycosis among a highway construction crew.
AB  - Coccidioidomycosis is an infection caused by inhaling spores of the soil fungus
      Coccidioides immitis (hereafter termed Cocci). Cocci is endemic in certain areas
      of California. When soil containing the fungus is disturbed, as during earth
      moving activities, respirable Cocci spores can become airborne and be inhaled by
      persons in the vicinity. This article describes a cluster of seven
      Cocciodioidomycosis cases among a highway construction crew that occurred in
      June/July 2008 in Kern County, CA, which is among the most highly endemic regions
      for Cocci in California. The exposures spanned no more than seven work days, and
      illness developed within two to three weeks of the exposures. Given the common
      source of exposure (soil dust generated at the work site) and the multiple cases
      occurring close in time, the cluster can also be termed a "point-source
      outbreak." The contractor was not informed of the infection risk and did not take
      adequate precautions against dust exposure. Appropriate
      engineering/administrative controls and respiratory protection are discussed.

PMID- 29053942
TI  - Do elite breath-hold divers suffer from mild short-term memory impairments?
AB  - Repeated apneas are associated with severe hypoxemia that may ultimately lead to
      loss of consciousness in some breath-hold divers. Despite increasing number of
      practitioners, the relationship between apnea-induced hypoxia and neurocognitive
      functions is still poorly understood in the sport of free diving. To shed light
      onto this phenomenon, we examined the impact of long-term breath-hold diving
      training on attentional processing, short-term memory, and long-term mnesic and
      executive functions. Thirty-six men matched for age, height, and weight were
      separated into the following 3 groups: (i) 12 elite breath-hold divers (EBHD),
      mean static apnea best time 371 s, 105 months mean apnea experience; (ii) 12
      novice breath-hold divers, mean best time 243 s, 8.75 months mean apnea
      experience; and (iii) 12 physical education students with no breath-hold diving
      experience; all of these participants performed varied written and computerized
      neuropsychological tasks. Compared with the 2 other groups, the EBHD group was
      slower to complete the interference card during a Stroop test (F[1,33] = 4.70, p
      < 0.05), and presented more errors on the interference card (F[1,33] = 2.96, p <
      0.05) and a lower total interference score (F[1,33] = 5.64, p < 0.05). The time
      to complete the interference card test was positively correlated with maximal
      static apnea duration (r = 0.73, p < 0.05) and the number of years of breath-hold
      diving training (r = 0.79, p < 0.001). These findings suggest that breath-hold
      diving training over several years may cause mild, but persistent, short-term
      memory impairments.

PMID- 29053943
TI  - Inflammation status of healthy young men: initial and specific responses to
      resistance training.
AB  - Our primary aim was to study the effects of a 4-week preparatory resistance
      training (RT) period followed by 12 weeks of 2 specific RT protocols (either
      hypertrophic-strength (HS) or strength-hypertrophy-power training) on
      inflammation markers and the possible relationship of the changes in abdominal
      fat and lean mass to the changes in inflammation status. A total of 82 healthy
      men were included in the study. Maximal concentric leg press strength (1
      repetition maximum), total body lean mass, total body and abdominal fat mass,
      circulating high-sensitivity C-reactive protein, interleukin-6, interleukin-1
      receptor antagonist (IL-1ra), monocyte chemoattractant protein 1 (MCP-1), and
      selected adipocytokines (resistin, adiponectin, and leptin) concentrations were
      measured before and after 4 (wk4) and 16 weeks (wk16) of RT. After the initial
      phase of RT, on wk4, abdominal and total fat mass as well as plasma leptin
      concentrations were significantly reduced (p < 0.05), whereas muscle mass, IL
      1ra, resistin, and MCP-1 concentrations were significantly increased (p < 0.05).
      During specialized training phase, at wk16, only HS led to further reduction in
      abdominal and total fat mass, resistin, and leptin (p < 0.05), whereas both
      training modes led to lower MCP-1 concentrations (p < 0.05). Abdominal fat mass
      and circulating leptin were reduced already after 4 weeks of RT. Simultaneously,
      circulating MCP-1 and resistin concentrations increased, possibly as markers of
      muscle adaptation and regeneration. The present findings also suggest that RT
      with hypertrophic focus is beneficial for further reductions in abdominal fat
      mass and to decrease circulating inflammatory markers.

PMID- 29053944
TI  - Investigation of the C-3-epi-25(OH)D3 of 25-hydroxyvitamin D3 in urban
      schoolchildren.
AB  - The physiological relevance C-3 epimer of 25-hydroxyvitamin D (3-epi-25(OH)D) is
      not well understood among youth. The objective of this study was to assess
      whether demographic/physiologic characteristics were associated with 3-epi
      25(OH)D3 concentrations in youth. Associations between 3-epi-25(OH)D3 and
      demographics and between 3-epi-25(OH)D3, total 25-hydroxyvitamin (25(OH)D)
      (25(OH)D2 + 25(OH)D3), total cholesterol, high-density lipoprotein, low-density
      lipoprotein, and triglycerides were examined in racially/ethnically diverse
      schoolchildren (n = 682; age, 8-15 years) at Boston-area urban schools.
      Approximately 50% of participants had detectable 3-epi-25(OH)D3 (range 0.95-3.95
      ng/mL). The percentage of 3-epi-25(OH)D3 of total 25(OH)D ranged from 2.5% to
      17.0% (median 5.5%). Males were 38% more likely than females to have detectable 3
      epi-25(OH)D3 concentrations. Both Asian and black race/ethnicity were associated
      with lower odds of having detectable 3-epi-25(OH)D3 compared with non-Hispanic
      white children (Asian vs. white, odds ratio (OR) 0.28, 95% confidence interval
      (CI) 0.14-0.53; black vs. white, OR 0.38, 95%CI 0.23-0.63, p < 0.001). Having an
      adequate (20-29 ng/mL) or optimal (>30 ng/mL) 25(OH)D concentration was
      associated with higher odds of having detectable 3-epi-25(OH)D3 than having an
      inadequate (<20 ng/mL) concentration (OR 4.78, 95%CI 3.23-6.94 or OR 14.10, 95%CI
      7.10-28.0, respectively). There was no association between 3-epi-25(OH)D3 and
      blood lipids. However, when considering 3-epi-25(OH)D3 as a percentage of total
      25(OH)D, total cholesterol was lower in children with percent 3-epi-25(OH)D3
      above the median (mean difference -7.1 mg/dL, p = 0.01). In conclusion, among
      schoolchildren, sex, race/ethnicity, and total serum 25(OH)D concentration is
      differentially associated with 3-epi-25(OH)D. The physiological relevance of 3
      epi-25(OH)D3 may be related to the 3-epi-25(OH)D3 as a percentage of total
      25(OH)D and should be considered in future investigations.

PMID- 29053945
TI  - Tree uptake of excess nutrients and herbicides in a maize-olive tree cultivation
      system.
AB  - Due to the extent of non-point source agricultural pollution, protective measures
      to control agrochemicals from entering aquatic systems are necessary. Measures
      may include, among others, vegetated buffer strips (VFS), no spray buffer zones,
      alley crops and agroforestry systems (AFS). The scope of the present work is to
      examine the pollution abatement potential of a maize-olive (MO) AFS. The
      efficiency of a combined MO trees system in reducing nutrients and herbicides is
      tested through soil monitoring in an experimental plot, located in Koropi,
      Eastern Attica, Greece, in the period May 2015 to November 2015. The monitored
      pollutants were nitrogen and phosphorus, as well as two herbicides: pendimethalin
      and nicosulfuron. Soil samples were collected every 3-5 weeks at various soil
      horizons and distances from the tree row. Pollutant concentrations were
      determined using liquid chromatography tandem mass spectrometry (LC-MS/MS), ion
      chromatography (IC) and spectrophotometry techniques. The studied MO tree system
      exhibited the potential to reduce pollutant migration, with removals ranging 36.8
      78.9% for [Formula: see text], 79.3-100% for [Formula: see text], 76.7-100% for
      [Formula: see text], 79.4-100% for [Formula: see text] and 70-100% for the
      examined herbicides. The higher removal percentages were observed in the upper
      soil layers (5-35 cm, below the crops), and where the finer tree roots extend.
      Thus, the results indicate that planting of trees in cultivated fields can
      contribute to the reduction of agrochemical pollution of the subsurface soil and
      in extension of groundwater.

PMID- 29053946
TI  - Measurement of area and personal breathing zone concentrations of diesel
      particulate matter (DPM) during oil and gas extraction operations, including
      hydraulic fracturing.
AB  - Diesel engines serve many purposes in modern oil and gas extraction activities.
      Diesel particulate matter (DPM) emitted from diesel engines is a complex aerosol
      that may cause adverse health effects depending on exposure dose and duration.
      This study reports on personal breathing zone (PBZ) and area measurements for DPM
      (expressed as elemental carbon) during oil and gas extraction operations
      including drilling, completions (which includes hydraulic fracturing), and
      servicing work. Researchers at the National Institute for Occupational Safety and
      Health (NIOSH) collected 104 full-shift air samples (49 PBZ and 55 area) in
      Colorado, North Dakota, Texas, and New Mexico during a four-year period from 2008
      2012. The arithmetic mean (AM) of the full shift TWA PBZ samples was 10 ug/m3;
      measurements ranged from 0.1-52 ug/m3. The geometric mean (GM) for the PBZ
      samples was 7 ug/m3. The AM of the TWA area measurements was 17 ug/m3 and ranged
      from 0.1-68 ug/m3. The GM for the area measurements was 9.5 ug/m3. Differences
      between the GMs of the PBZ samples and area samples were not statistically
      different (P > 0.05). Neither the Occupational Safety and Health Administration
      (OSHA), NIOSH, nor the American Conference of Governmental Industrial Hygienists
      (ACGIH) have established occupational exposure limits (OEL) for DPM. However, the
      State of California, Department of Health Services lists a time-weighted average
      (TWA) OEL for DPM as elemental carbon (EC) exposure of 20 ug/m3. Five of 49
      (10.2%) PBZ TWA measurements exceeded the 20 ug/m3 EC criterion. These
      measurements were collected on Sandmover and Transfer Belt (T-belt) Operators,
      Blender and Chemical Truck Operators, and Water Transfer Operators during
      hydraulic fracturing operations. Recommendations to minimize DPM exposures
      include elimination (locating diesel-driven pumps away from well sites),
      substitution, (use of alternative fuels), engineering controls using advanced
      emission control technologies, administrative controls (configuration of well
      sites), hazard communication, and worker training.

PMID- 29053947
TI  - A Bitter Tale of Sweet Synergy.
AB  - Some sweeteners show a synergistic enhancement of perceived sweetness when they
      are tasted as binary mixtures. In this issue of Cell Chemical Biology, Behrens et
      al. (2017) find that a surprising explanation for this classic observation may
      lie in their reciprocal inhibition of bitter taste receptors.

PMID- 29053948
TI  - Nanoscale Imaging Reveals Big Role for Iron in Alzheimer's Disease.
AB  - In this issue of Cell Chemical Biology, Telling et al. (2017) apply advanced X
      ray microscopy techniques to reveal magnetite iron species in plaques from a
      mouse model of Alzheimer's disease. The characterization of abnormal iron
      chemistry in the disease model highlights the potential for iron to combine with
      the beta-amyloid peptide and accelerate the disease process.

PMID- 29053949
TI  - Unpackaging the Roles of Streptomyces Natural Products.
AB  - Streptomyces are the principle source of antibiotics in clinical use, but what
      the bacteria use these molecules for remains largely a mystery. In this issue of
      Cell Chemical Biology, Hoefler et al. (2017) demonstrate a direct link between
      biosynthesis of the polyketide linearmycins and extracellular membrane vesicles.

PMID- 29053950
TI  - More than One Way to Skin a Catalyst.
AB  - In this issue of Cell Chemical Biology, Diaz et al. (2017) report a strategy to
      achieve temporal, spatial, and stoichiometric control over the protein kinase
      cAbl in living cells. They achieve this by splitting cAbl into two inactive
      fragments that form an active kinase upon small molecule addition, potentially
      providing a general way to probe the wiring of signal transduction networks.

PMID- 29053952
TI  - Unexpected Alliance of WHIP-TRIM14-PPP6C to Combat Viruses.
AB  - In this issue of Molecular Cell, Tan et al. (2017) provide novel perspectives
      into the regulatory role of WHIP-TRIM14-PPP6C signalosome in enhancing RIG-I
      mediated viral RNA sensing pathway.

PMID- 29053951
TI  - Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell
      Mitochondria.

PMID- 29053953
TI  - Histone H3 Dual Ubiquitylation Mediates Maintenance DNA Methylation.
AB  - Epigenetic marks, including DNA methylation and posttranslational modifications
      (PTMs) in histones, are important factors in determining the fate of replicating
      cells. In this issue of Molecular Cell, Ishiyama et al. (2017) reveal yet another
      layer in a remarkably complex mechanism of maintenance DNA methylation.

PMID- 29053954
TI  - Spt6 Gets in the Way of Polycomb to Promote ESC Pluripotency.
AB  - Despite expressing high levels of Polycomb group proteins, embryonic stem cells
      (ESCs) are refractory to H3K27 trimethylation, notably at super-enhancers
      regulating key pluripotency genes. In this issue of Molecular Cell, Wang et al.
      (2017) report that the histone chaperone Spt6 prevents H3K27 trimethylation of
      key ESC super-enhancers.

PMID- 29053955
TI  - The Met1-Linked Ubiquitin Machinery: Emerging Themes of (De)regulation.
AB  - The linear ubiquitin chain assembly complex, LUBAC, is the only known mammalian
      ubiquitin ligase that makes methionine 1 (Met1)-linked polyubiquitin (also
      referred to as linear ubiquitin). A decade after LUBAC was discovered as a
      cellular activity of unknown function, there are now many lines of evidence
      connecting Met1-linked polyubiquitin to NF-kappaB signaling, cell death,
      inflammation, immunity, and cancer. We now know that Met1-linked polyubiquitin
      has potent signaling functions and that its deregulation is connected to disease.
      Indeed, mutations and deficiencies in several factors involved in conjugation and
      deconjugation of Met1-linked polyubiquitin have been implicated in immune-related
      disorders. Here, we discuss current knowledge and recent insights into the role
      and regulation of Met1-linked polyubiquitin, with an emphasis on the mechanisms
      controlling the function of LUBAC.

PMID- 29053956
TI  - Assembly of the WHIP-TRIM14-PPP6C Mitochondrial Complex Promotes RIG-I-Mediated
      Antiviral Signaling.
AB  - Mitochondrial antiviral signaling platform protein (MAVS) acts as a central hub
      for RIG-I receptor proximal signal propagation. However, key components in the
      assembly of the MAVS mitochondrial platform that promote RIG-I mitochondrial
      localization and optimal activation are still largely undefined. Employing pooled
      RNAi and yeast two-hybrid screenings, we report that the mitochondrial adaptor
      protein tripartite motif (TRIM)14 provides a docking platform for the assembly of
      the mitochondrial signaling complex required for maximal activation of RIG-I
      mediated signaling, consisting of WHIP and protein phosphatase PPP6C. Following
      viral infection, the ubiquitin-binding domain in WHIP bridges RIG-I with MAVS by
      binding to polyUb chains of RIG-I at lysine 164. The ATPase domain in WHIP
      contributes to stabilization of the RIG-I-dsRNA interaction. Moreover,
      phosphatase PPP6C is responsible for RIG-I dephosphorylation. Together, our
      findings define the WHIP-TRIM14-PPP6C mitochondrial signalosome required for RIG
      I-mediated innate antiviral immunity.

PMID- 29053957
TI  - CDK4 Phosphorylates AMPKalpha2 to Inhibit Its Activity and Repress Fatty Acid
      Oxidation.
AB  - The roles of CDK4 in the cell cycle have been extensively studied, but less is
      known about the mechanisms underlying the metabolic regulation by CDK4. Here, we
      report that CDK4 promotes anaerobic glycolysis and represses fatty acid oxidation
      in mouse embryonic fibroblasts (MEFs) by targeting the AMP-activated protein
      kinase (AMPK). We also show that fatty acid oxidation (FAO) is specifically
      induced by AMPK complexes containing the alpha2 subunit. Moreover, we report that
      CDK4 represses FAO through direct phosphorylation and inhibition of AMPKalpha2.
      The expression of non-phosphorylatable AMPKalpha2 mutants, or the use of a CDK4
      inhibitor, increased FAO rates in MEFs and myotubes. In addition, Cdk4-/- mice
      have increased oxidative metabolism and exercise capacity. Inhibition of CDK4
      mimicked these alterations in normal mice, but not when skeletal muscle was AMPK
      deficient. This novel mechanism explains how CDK4 promotes anabolism by blocking
      catabolic processes (FAO) that are activated by AMPK.

PMID- 29053958
TI  - Structure of the Dnmt1 Reader Module Complexed with a Unique Two-Mono-Ubiquitin
      Mark on Histone H3 Reveals the Basis for DNA Methylation Maintenance.
AB  - The proper location and timing of Dnmt1 activation are essential for DNA
      methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono
      ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and
      activation at DNA methylation sites. The crystal structure of the replication
      foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals
      striking differences to the known ubiquitin-recognition structures. The two
      ubiquitins are simultaneously bound to the RFTS with a combination of canonical
      hydrophobic and atypical hydrophilic interactions. The C-lobe of RFTS, together
      with the K23Ub surface, also recognizes the N-terminal tail of H3. The binding of
      H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS,
      suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3
      K18Ub/23Ub increases its catalytic activity in vitro. Our results therefore shed
      light on the essential role of a unique ubiquitin-binding module in DNA
      methylation maintenance.

PMID- 29053959
TI  - Restoration of Replication Fork Stability in BRCA1- and BRCA2-Deficient Cells by
      Inactivation of SNF2-Family Fork Remodelers.
AB  - To ensure the completion of DNA replication and maintenance of genome integrity,
      DNA repair factors protect stalled replication forks upon replication stress.
      Previous studies have identified a critical role for the tumor suppressors BRCA1
      and BRCA2 in preventing the degradation of nascent DNA by the MRE11 nuclease
      after replication stress. Here we show that depletion of SMARCAL1, a SNF2-family
      DNA translocase that remodels stalled forks, restores replication fork stability
      and reduces the formation of replication stress-induced DNA breaks and
      chromosomal aberrations in BRCA1/2-deficient cells. In addition to SMARCAL1,
      other SNF2-family fork remodelers, including ZRANB3 and HLTF, cause nascent DNA
      degradation and genomic instability in BRCA1/2-deficient cells upon replication
      stress. Our observations indicate that nascent DNA degradation in BRCA1/2
      deficient cells occurs as a consequence of MRE11-dependent nucleolytic processing
      of reversed forks generated by fork remodelers. These studies provide mechanistic
      insights into the processes that cause genome instability in BRCA1/2-deficient
      cells.

PMID- 29053961
TI  - Maturation of Xenopus laevis oocytes under cadmium and lead exposures: Cell
      biology investigations.
AB  - Since amphibians are recognised as good models to assess the quality of
      environments, only few studies have dealt with the impacts of chemical
      contaminants on their gametes, while toxic effects at this stage will alter all
      the next steps of their life cycle. Therefore, we propose to investigate the
      oocyte maturation of Xenopus laevis in cadmium- and lead-contaminated conditions.
      The impacts of cadmium and lead ions were explored on events involved in the
      hormone-dependent process of maturation. In time-course experiments, cadmium, at
      the highest concentration, delayed and prevented the germinal vesicle breakdown.
      Even in the absence of progesterone this ion could also induce it. No such
      spontaneous maturation was observed after lead exposures. An acceleration of the
      process at the highest tested concentration of lead (90MUM), in presence of
      progesterone, was recorded. Cytological observations highlighted that cadmium
      exposures drove severe disturbances of meiotic spindle morphogenesis. At last,
      cadmium exposures altered the MAPK pathway, regarding the activation of ERK2 and
      RSK, but also the activation and the activity of the MPF, by disturbing the state
      of phosphorylation of Cdc2 and histone H3. Xenopus laevis oocytes were affected
      by these metal ion exposures, notably by Cd2+. Signatures of these metal
      exposures on the oocyte maturation were detected. This germ cell appeared to be a
      relevant model to assess the effects of environmental contaminants such as
      metals.

PMID- 29053960
TI  - A General Strategy for Discovery of Inhibitors and Activators of RING and U-box
      E3 Ligases with Ubiquitin Variants.
AB  - RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and
      have been implicated in numerous diseases, but targeting these enzymes remains a
      major challenge. We report the development of three ubiquitin variants (UbVs),
      each binding selectively to the RING or U-box domain of a distinct E3 ligase:
      monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and
      biochemical analyses revealed that UbVs specifically inhibited the activity of
      UBE4B or phosphorylated CBL by blocking the E2~Ub binding site. Surprisingly, the
      UbV selective for dimeric XIAP formed a dimer to stimulate E3 activity by
      stabilizing the closed E2~Ub conformation. We further verified the inhibitory and
      stimulatory functions of UbVs in cells. Our work provides a general strategy to
      inhibit or activate RING/U-box E3 ligases and provides a resource for the
      research community to modulate these enzymes.

PMID- 29053962
TI  - Identification of up-regulated genes from the metal-hyperaccumulator aquatic fern
      Salvinia minima Baker, in response to lead exposure.
AB  - Lead (Pb) is one of the most serious environmental pollutants. The aquatic fern
      Salvinia minima Baker is capable to hyper-accumulate Pb in their tissues.
      However, the molecular mechanisms involved in its Pb accumulation and tolerance
      capacity are not fully understood. In order to investigate the molecular
      mechanisms that are activated by S. minima in response to Pb, we constructed a
      suppression subtractive hybridization library (SSH) in response to an exposure to
      40MUM of Pb(NO3)2 for 12h. 365 lead-related differentially expressed sequences
      tags (ESTs) were isolated and sequenced. Among these ESTs, 143 unique cDNA (97
      were registered at the GenBank and 46 ESTs were not registered, because they did
      not meet the GenBank conditions). Those ESTs were identified and classified into
      3 groups according to Blast2GO. In terms of metabolic pathways, they were grouped
      into 29 KEGG pathways. Among the ESTs, we identified some that might be part of
      the mechanism that this fern may have to deal with this metal, including abiotic
      stress-related transcription factors, some that might be involved in tolerance
      mechanisms such as ROS scavenging, membrane protection, and those of cell
      homeostasis recovery. To validate the SSH library, 4 genes were randomly selected
      from the library and analyzed by qRT-PCR. These 4 genes were transcriptionally up
      regulated in response to lead in at least one of the two tested tissues (roots
      and leaves). The present library is one of the few genomics approaches to study
      the response to metal stress in an aquatic fern, representing novel molecular
      information and tools to understand the molecular physiology of its Pb tolerance
      and hyperaccumulation capacity. Further research is required to elucidate the
      functions of the lead-induced genes that remain classified as unknown, to perhaps
      reveal novel molecular mechanisms of Pb tolerance and accumulation capacity in
      aquatic plants.

PMID- 29053963
TI  - Hydrilla verticillata employs two different ways to affect DNA methylation under
      excess copper stress.
AB  - Because of the accumulation of heavy metals, Hydrilla verticillata (L.f.) Royle,
      a rooted submerged perennial aquatic herb, is being developed as a potential tool
      to clean the aquatic ecosystem polluted by heavy metals. However, its
      physiological responses for heavy metal remain to be elucidated. Here, through
      employing proteomics approach, we found that excess Cu significantly induced the
      expressions of four DNA methylation related proteins in H. verticillata, which
      were the homologues of two domains rearranged methyltransferases (DRM), a
      methyltransferases chromomethylase (CMT) and a histone H3 lysine-9 specific SUVH6
      like (SUVH6). Consistently, a dramatic change in DNA methylation patterns was
      detected in excess Cu-exposed H. verticillata. Surprisingly, administration of
      the NADPH oxidase inhibitors, diphenylene iodonium (DPI) and imidazole (IMZ) that
      block production of reactive oxygen species (ROS) could trigger the remethylation
      of genomic sites that were demethylated by excess Cu, indicating that Cu-induced
      ROS might be another way to affect DNA methylation. Further analysis suggested
      this changed DNA methylation may be owing to the ROS-induced DNA damage. Taken
      together, our findings demonstrate that two different ways to influence DNA
      methylation in excess Cu-treated H. verticillata.

PMID- 29053964
TI  - The Coming Peptide Tidal Wave.

PMID- 29053965
TI  - FUS Zigzags Its Way to Cross Beta.
AB  - The low-complexity domain (LCD) of the FUS protein forms concentration-dependent
      assemblies, including liquid droplets and fibril-based hydrogels. The molecular
      structures of FUS within different assemblies and their functional relevance are
      subjects of intense debate. Murray et al. report an atomic-level structural model
      for FUS LCD fibrils that answers some questions and raises new ones.

PMID- 29053966
TI  - Transforming Lipoxygenases: PE-Specific Enzymes in Disguise.
AB  - In this issue of Cell, Wenzel et al. solve a long-standing mystery regarding how
      damage to cell membranes occurs during ferroptosis, an iron-dependent form of
      regulated cell death. They found that lipoxygenases are like Transformer toys,
      being converted from one enzyme type to another in the presence of the protein
      PEBP1.

PMID- 29053967
TI  - Friends in Low Places: Intestinal Commensals Limit Colitis through Molecular
      Mimicry.
AB  - Inflammatory bowel disease is thought to arise from inappropriate inflammation to
      gut bacteria, yet mechanisms preventing these responses remain elusive. In this
      issue of Cell, Nanjundappa et al. report that Bacteroides share an epitope with a
      pancreas-specific peptide that induces protective CD8+ T cells, identifying
      molecular mimicry as a mechanism to enforce tolerance in the gut.

PMID- 29053968
TI  - Multiscale 3D Genome Rewiring during Mouse Neural Development.
AB  - Chromosome conformation capture technologies have revealed important insights
      into genome folding. Yet, how spatial genome architecture is related to gene
      expression and cell fate remains unclear. We comprehensively mapped 3D chromatin
      organization during mouse neural differentiation in vitro and in vivo, generating
      the highest-resolution Hi-C maps available to date. We found that transcription
      is correlated with chromatin insulation and long-range interactions, but dCas9
      mediated activation is insufficient for creating TAD boundaries de novo.
      Additionally, we discovered long-range contacts between gene bodies of exon-rich,
      active genes in all cell types. During neural differentiation, contacts between
      active TADs become less pronounced while inactive TADs interact more strongly. An
      extensive Polycomb network in stem cells is disrupted, while dynamic interactions
      between neural transcription factors appear in vivo. Finally, cell type-specific
      enhancer-promoter contacts are established concomitant to gene expression. This
      work shows that multiple factors influence the dynamics of chromatin interactions
      in development.

PMID- 29053969
TI  - PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death
      Signals.
AB  - Ferroptosis is a form of programmed cell death that is pathogenic to several
      acute and chronic diseases and executed via oxygenation of polyunsaturated
      phosphatidylethanolamines (PE) by 15-lipoxygenases (15-LO) that normally use free
      polyunsaturated fatty acids as substrates. Mechanisms of the altered 15-LO
      substrate specificity are enigmatic. We sought a common ferroptosis regulator for
      15LO. We discovered that PEBP1, a scaffold protein inhibitor of protein kinase
      cascades, complexes with two 15LO isoforms, 15LO1 and 15LO2, and changes their
      substrate competence to generate hydroperoxy-PE. Inadequate reduction of
      hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4,
      leads to ferroptosis. We demonstrated the importance of PEBP1-dependent
      regulatory mechanisms of ferroptotic death in airway epithelial cells in asthma,
      kidney epithelial cells in renal failure, and cortical and hippocampal neurons in
      brain trauma. As master regulators of ferroptotic cell death with profound
      implications for human disease, PEBP1/15LO complexes represent a new target for
      drug discovery.

PMID- 29053972
TI  - SnapShot: Angiopoietins and Their Functions.
AB  - Angiopoietins signal through TIE receptors to control both developmental and
      homeostatic processes that can go awry in genetic diseases and cancer. This
      SnapShot illustrates key elements of angiopoietin signaling in normal and disease
      contexts.

PMID- 29053971
TI  - A Gut Microbial Mimic that Hijacks Diabetogenic Autoreactivity to Suppress
      Colitis.
AB  - The gut microbiota contributes to the development of normal immunity but, when
      dysregulated, can promote autoimmunity through various non-antigen-specific
      effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase
      expressed by several species of the gut microbial genus Bacteroides encodes a low
      avidity mimotope of the pancreatic beta cell autoantigen islet-specific glucose-6
      phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free
      mice monocolonized with integrase-competent, integrase-deficient, and integrase
      transgenic Bacteroides demonstrate that the microbial epitope promotes the
      recruitment of diabetogenic CD8+ T cells to the gut. There, these effectors
      suppress colitis by targeting microbial antigen-loaded, antigen-presenting cells
      in an integrin beta7-, perforin-, and major histocompatibility complex class I
      dependent manner. Like their murine counterparts, human peripheral blood T cells
      also recognize Bacteroides integrase. These data suggest that gut microbial
      antigen-specific cytotoxic T cells may have therapeutic value in inflammatory
      bowel disease and unearth molecular mimicry as a novel mechanism by which the gut
      microbiota can regulate normal immune homeostasis. PAPERCLIP.

PMID- 29053970
TI  - mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from
      Lysosomes and Use Protein as a Nutrient.
AB  - The mTORC1 kinase is a master growth regulator that senses many environmental
      cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a
      poorly understood lysosomal membrane protein with homology to amino acid
      transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1
      pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid
      homeostasis. SLC38A9 mediates the transport, in an arginine-regulated fashion, of
      many essential amino acids out of lysosomes, including leucine, which mTORC1
      senses through the cytosolic Sestrin proteins. SLC38A9 is necessary for leucine
      generated via lysosomal proteolysis to exit lysosomes and activate mTORC1.
      Pancreatic cancer cells, which use macropinocytosed protein as a nutrient source,
      require SLC38A9 to form tumors. Thus, through SLC38A9, arginine serves as a
      lysosomal messenger that couples mTORC1 activation to the release from lysosomes
      of the essential amino acids needed to drive cell growth.

PMID- 29053973
TI  - Duration of moderate to vigorous daily activity is negatively associated with
      slow walking speed independently from step counts in elderly women aged 75 years
      or over: A cross-sectional study.
AB  - OBJECTIVES: This study aimed 1) to examine whether objectively measured duration
      of moderate to vigorous physical activity (MVPA) was associated with slow walking
      speed, independent from step counts, in elderly women aged 75 or over (old-old)
      and 2) to determine a possible cut-off value for duration of MVPA related to slow
      walking speed. METHODS: Participants were 350 community-dwelling old-old women.
      Slow walking speed was defined as usual walking speed <1.0m/s. Duration of MVPA
      (activity at an intensity >3 metabolic equivalents) and number of step counts
      were measured using a uniaxial accelerometer over 1 wk. Body mass index, grip
      strength, back and leg pain, cognitive function, executive function, and presence
      of depression were also assessed. Participants with missing data were excluded
      from the main analysis. RESULTS: The mean age of the participants was 79.9+/-3.6
      y. The prevalence of slow walking speed was 14.9%. Multiple logistic regression
      analysis showed that the duration of MVPA was significantly and inversely
      associated with slow walking speed, independent from step counts and other
      confounding factors (adjusted odds ratio=0.94 per 1min/d increment, 95%
      confidence interval=0.73-0.99; p=0.031). This relationship was also observed in
      sensitivity analysis that included all participants. A MVPA cut-off value of
      8.7min/d was determined using the receiver operating characteristic analysis.
      CONCLUSION: The findings from the present study suggest that promoting MVPA may
      be helpful to prevent slow walking speed. The validity of MVPA for predicting
      slow walking speed needs to be confirmed in future prospective studies.

PMID- 29053974
TI  - Depression as seen through the eyes of rural Chinese women: Implications for help
      seeking and the future of mental health care in China.
AB  - BACKGROUND: As part of a larger epidemiological study of depression among rural
      Chinese women, we sought to understand their explanatory models of depression. We
      explored how participants describe depression, to what cause they attribute
      depression, and what sources of treatment they would recommend. METHODS:
      Participants first were assessed with the Center for Epidemiological-Depression
      scale (CES-D), with a cut-point of 16 or greater indicative of depression. The
      Short Explanatory Model Interview (SEMI), a semi-structured questionnaire, was
      our primary tool for exploring participants' explanatory models relating to a
      vignette describing a rural Chinese woman with depression. RESULTS: Among the 416
      women who consented and completed the SEMI, 277(66.6%) reported that the woman in
      the vignette had something wrong with her health. Among these, only 8(2.9%) women
      provided a specific psychiatric name for the condition, while 150(54.2%) provided
      non-specific psychiatric disease names or affective symptoms, and 78(28.2%)of the
      sample provided physical disease names. Participants attributed causes largely to
      internal factors (41.5%) or external factors (36.8%). In terms of help-seeking,
      101(36.4%) said the woman in the vignette should see a doctor, 70(25.3%)
      indicated that she should solve the problem herself, and 42(15.2%) recommended
      seeking support from family members and friends. We did not find any differences
      in recognition, causal attribution, and help-seeking suggestions between women
      with a CES-D >= 16 and those with CES-D < 16. LIMITATIONS: The use of a vignette
      to prompt discussion was not the same as talking about real-life personal
      situations. CONCLUSION: Our results point to potential challenges and
      opportunities that lay ahead as China develops mental health services in its vast
      rural areas among women who may be at risk for developing depression. We found
      that our participants often attributed their symptoms to internal or external
      social causes, and preferred not speaking with family members and friends. Our
      findings suggest that rural Chinese women may be reticent to recognize or
      describe categorical concepts such as "depression" as a health problem, and they
      invite further consideration about how best to develop new health services in
      China's rural regions.

PMID- 29053976
TI  - Longitudinal association between mental disorders in childhood and subsequent
      depression - A nationwide prospective cohort study.
AB  - BACKGROUND: Depression ranges among the most impairing mental disorders
      worldwide, and early detection is a global health priority. Little is known about
      the association between non-affective mental disorders in childhood/adolescence
      and later depression. METHODS: Nationwide register-based prospective cohort
      study, estimating cumulative incidences and incidence rate ratios (IRR) for later
      depression in individuals with and without non-affective mental disorders in
      early life. RESULTS: 475,213 females and 484,813 males born 1990-2007 were
      followed for a mean of 9.14 years (contributing a total of 8778,331 person-years
      of observation). In the cohort, 7963 (5451 females) were diagnosed with
      depression. Depression was more common in individuals with prior non-affective
      mental disorders in adolescence (15.98% in females and 7.02% in males) and in
      childhood (4.98% in females and 1.6% in males), than in the background population
      (3.94% and 1.3% in females; 1.37% and 0.47% in males). Eating and anxiety
      disorders in childhood/adolescence carried the highest absolute risk of
      depression. The relative risk of depression was particularly high the first year
      after the first non-affective disorder (IRR = 15.5; 14.07-17.10), but remained
      highly elevated more than five years after the first non-affective diagnosis (IRR
      = 2.05; 1.84-2.28), when compared to young people without such disorders.
      LIMITATIONS: This study only included diagnoses given at hospital departments,
      representing the more severe mental disorders. CONCLUSIONS: Children and
      adolescents with non-affective mental disorders were at substantially increased
      absolute and relative risk of developing depression in young adulthood,
      especially females diagnosed with anxiety- or eating disorders in adolescence.
      These findings may help identify groups of children and adolescents at very high
      risk of developing depression.

PMID- 29053975
TI  - Depression among female heads-of-household in rural Mozambique: A cross-sectional
      population-based survey.
AB  - BACKGROUND: An estimated 350 million people live with depression worldwide. In
      Mozambique, there are no national data quantifying the burden of mental
      illnesses. With the sixth highest suicide rate in the world, there is strong
      evidence of an unmet mental health need. We conducted a survey to measure the
      prevalence of depression among female heads of household and assess individual,
      social, and cultural risk factors associated with a positive depression
      screening. METHODS: This survey was conducted across 14 rural districts in
      central Mozambique in 2014. We gathered information from 3543 female heads of
      household (100% response rate) on > 500 variables, including a depression
      screening tool (PHQ-8). Weighted percentages of survey responses are reported.
      RESULTS: Among female heads of household, 14% screened positive for depression
      (PHQ-8 score >= 10). Our adjusted models show increased odds of depression per
      additional year of age (aOR: 1.02 [1.01, 1.04]; p = 0.002), additional year of
      education (aOR: 1.06 [1.02, 1.11]; p = 0.006), and additional kilometer from the
      nearest clinic (aOR: 1.05 [1.02, 1.07]; p = < 0.001). Experiencing food
      insecurity (aOR: 1.05 [1.02, 1.08]; p = 0.003) was associated with increased odds
      of depression. Being single (aOR: 0.42 [0.29, 0.60]) or
      divorced/widowed/separated (aOR: 0.57 [0.34, 0.98]; p < 0.001) vs. married was
      protective against depression, as was a perceived "sufficient" household income
      (aOR: 0.37 [0.19, 0.69]; p = 0.008). LIMITATIONS: Social desirability bias may
      have led women to underreport feelings of depression. CONCLUSIONS: The
      association of more education and marriage with increased odds of depression may
      reflect a frustration with limited opportunity for success experienced by some
      women in rural Mozambique.

PMID- 29053977
TI  - Suicidal ideation declines with improvement in the subjective symptoms of major
      depression.
AB  - BACKGROUND: Suicidal ideation appears to be more strongly associated with
      subjective rather than neurovegetative symptoms of depression. Effective
      treatment, then, should produce reductions in suicidal ideation to the degree
      that these subjective symptoms are alleviated relative to treatment effects on
      other symptoms. METHODS: In a randomized clinical trial comparing paroxetine and
      bupropion for treatment of depression in patients with either suicidal ideation
      or past attempt, depression severity and suicidal ideation were assessed weekly
      during the 8-week study. Depression rating scales - the 24-item Hamilton
      Depression Rating Scale [HDRS] and the Beck Depression Scale [BDI] - were
      decomposed into symptom clusters based on our published factor analyses, and
      their change over time compared to changes on the Beck Scale for Suicidal
      Ideation [SSI]. RESULTS: Improvement in factor scores associated with subjective
      symptoms of depression - HDRS Psychic Depression, BDI Subjective Depression, and
      BDI Self-Blame - were the best predictors of declining scores on the SSI
      regardless of type of drug treatment. BDI Subjective Depression was the best
      single predictor in the context of all other significant univariate predictors,
      accounting for 31.4% of the variance in the change in SSI. The three factors
      together accounted for 35.3%. LIMITATIONS: This is a secondary analysis of
      clinical trial data, with fixed treatments. CONCLUSIONS: Effective treatments to
      reduce suicidal ideation are associated with the reduction of the subjective
      symptoms of depression, which may not always decline in synchrony with
      improvement in neurovegetative symptoms. This asynchrony may result in a period
      of elevated risk after the initiation of therapy. Data indicate that subjective
      depression symptoms should be a primary target in the treatment of depressed
      suicidal patients.

PMID- 29053978
TI  - Patterns of change in anxiety and depression during pregnancy predict preterm
      birth.
AB  - BACKGROUND: To determine whether changes in anxiety and depression during
      pregnancy influence the risk of having a preterm birth (PTB), and whether chronic
      stress modifies this relationship. METHODS: The data source for the current study
      is the All Our Babies prospective cohort (AOB). Anxiety and depression were
      measured at 17-24 weeks and again at 32-36 weeks' gestation using the Spielberg
      State Anxiety Scale and the Edinburgh Postnatal Depression Scale, respectively.
      Chronic stress was assessed at 17-24 weeks' gestation as a potential covariate,
      and was measured using the Perceived Stress Scale. Multivariable logistic
      regression modeling was used to assess each relationship RESULTS: Women who
      experienced an increase in anxiety scores, (time point 32-36 weeks, compared to
      the earlier time point 17-24 weeks), had 2.70 times higher odds of preterm
      delivery, compared to those with a reduction in anxiety scores (95% CI 1.28,
      5.69). Consistent low or high depression scores did not significantly influence
      the odds of PTB compared to a decrease in depression scores. A co-occurring
      increase in anxiety and depression scores was not found to increase the risk of
      PTB, and chronic stress did not modify any of these relationships. LIMITATIONS:
      This study was limited by a relatively small sample of women who delivered
      preterm, and therefore it was not possible to conduct additional analyses.
      Further, the analyses were limited to mostly late preterm infants (32-36 weeks'
      gestation). CONCLUSIONS: These findings should be validated with additional
      cohorts and a larger sample size. Ultimately, primary prevention could address
      anxiety during pregnancy.

PMID- 29053979
TI  - Associations between use of mood stabilizers and risk of cataract: A population
      based nested case-control study.
AB  - BACKGROUND: The aim of this study was to investigate whether use of mood
      stabilizers (MS) is associated with an increased risk of cataract development.
      METHODS: We conducted a nested case-control study using National Health Insurance
      Research Database in Taiwan. A total of 14,288 patients with bipolar disorder
      (BD) and schizophrenia were included; 7651 in the cataract group and 6637 in the
      control group. Based on overall cumulative period of MS (lithium, carbamazepine,
      valproate, and lamotrigine) treatment, we categorized into following groups: no
      use, and duration < 1 year, 1 to 2 years, and > 2 years. Conditional logistic
      regression analysis was used to explore the association between use of MS and
      risk of cataract development. RESULTS: The risks for cataract development were
      significantly higher in patients using lithium alone and lithium combined with
      other MS for more than 2 years (adjusted odd ratio [AOR] = 1.39; 95% CI = 1.01
      1.92, p = 0.043 and AOR = 1.44; 95% CI = 1.13-1.85, p = 0.003, respectively) than
      in non-users. Furthermore, the risks of cataract development increased in those
      treated with valproic acid combined with other MS (AOR = 1.26; 95% CI = 1.02
      1.57, p = 0.035). Finally, no increased risks of cataract development were found
      in carbamazepine and lamotrigine users. CONCLUSIONS: We found increased risks of
      cataract development in long-term users of lithium, lithium combined with other
      MS and valproic acid combined with other MS for more than two years among
      patients with BD and schizophrenia.

PMID- 29053980
TI  - Incident mental disorders in the aftermath of traumatic events: A prospective
      longitudinal community study.
AB  - BACKGROUND: Few strictly prospective-longitudinal community studies examined the
      role of traumatic events for risk of developing a broad range of incident mental
      disorders over several years. METHOD: A representative community sample of
      adolescents and young adults (n = 2797, baseline age 14-24) was prospectively
      examined in up to three assessment waves over up to 10 years. Traumatic events
      and DSM-IV mental disorders were assessed at each wave using the DIA-X/M-CIDI.
      Associations between traumatic events (meeting the DSM-IV A1-criterion for
      posttraumatic stress disorder, PTSD) or qualifying traumatic events (meeting the
      DSM-IV A2-criterion) at baseline and incident disorders at follow-up were tested
      with logistic regressions adjusted for gender and age. RESULTS: While traumatic
      and qualifying traumatic events at baseline were related to various baseline
      disorders, considerably fewer associations were found in strictly prospective
      analyses with incident disorders at follow-up as outcomes. After adjustment for
      baseline disorders, only (a) the association of traumatic events with incident
      specific phobias (Odds Ratio, OR = 1.6) and (b) the associations of qualifying
      traumatic events with incident specific phobias (OR = 1.6), PTSD (OR = 2.5) and
      major depressive episodes (OR = 1.4) remained significant. CONCLUSION: Targeted
      prevention and early intervention among traumatized individuals may be
      particularly beneficial to lower the incidence of specific phobias and MDE
      besides PTSD. LIMITATIONS: Associations between traumatic events and incident
      mental disorders might be underestimated, as cases developing psychopathology
      immediately after trauma exposure prior to baseline were excluded in our strictly
      prospective analyses.

PMID- 29053981
TI  - Clinical efficacy, onset time and safety of bright light therapy in acute bipolar
      depression as an adjunctive therapy: A randomized controlled trial.
AB  - BACKGROUND: Bright light therapy (BLT) is an effective treatment for seasonal
      affective disorder and non- seasonal depression. The efficacy of BLT in treating
      patients with bipolar disorder is still unknown. AIMS: The aim of this study is
      to examine the efficacy, onset time and clinical safety of BLT in treating
      patients with acute bipolar depression as an adjunctive therapy (trial
      registration at ClinicalTrials.gov: NCT02009371). METHODS: This was a multi
      center, single blind, randomized clinical trial. Seventy-four participants were
      randomized in one of two treatment conditions: BLT and control (dim red light
      therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT).
      Light therapy lasted for two weeks, one hour every morning. All participants were
      required to complete several scales assessments at baseline, and at the end of
      weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT
      which was assessed by the reduction rate of HAMD-17 scores, and the onset time of
      BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary
      outcome measures were rates of switch into hypomania or mania and adverse events.
      RESULTS: 1) Clinical efficacy: BLT showed a greater ameliorative effect on
      bipolar depression than the control, with response rates of 78.19% vs. 43.33%
      respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT
      group. 3) BLT-emergent hypomania: No participants experienced symptoms of
      hypomania. 4) Side effects: No serious adverse events were reported. CONCLUSION:
      BLT can be considered as an effective and safe adjunctive treatment for patients
      with acute bipolar depression.

PMID- 29053982
TI  - A longitudinal test of the predictions of the interpersonal-psychological theory
      of suicidal behaviour for passive and active suicidal ideation in a large
      community-based cohort.
AB  - BACKGROUND: The Interpersonal-Psychological Theory of Suicide (IPTS) aims to
      elucidate the key antecedents of suicide deaths. Limited research has tested the
      IPTS in a community setting, and very little longitudinal research has been
      conducted. The current study longitudinally tested the predictions of the IPTS
      for suicidal ideation in a large population-based sample. METHODS: The PATH
      through Life study assesses three age cohorts (20's, 40's, 60's) every four
      years. Two interpersonal factors were estimated at the third wave of assessment:
      thwarted belongingness (TB) and perceived burdensomeness (PB). The roles of these
      factors in suicide ideation (active and passive) four years later were estimated
      using logistic regression models (n = 4545). RESULTS: A one SD increase in TB was
      associated with increased odds of 37% for passive ideation and 24% for active
      ideation. For PB, odds were increased 2.5-fold for passive ideation and 2.4-fold
      for active ideation. A significant negative PB * TB interaction was found for
      passive but not active ideation. Effects were not consistent by age group or
      gender. LIMITATIONS: Proxy measures were used to assess the constructs. The
      extended timeframe and low prevalence of suicidal ideation limited power to find
      effects within subgroups. CONCLUSIONS: Although TB and PB were individually
      associated with suicidal thoughts, little evidence was found for the key
      predictions of the IPTS longitudinally. Further investigation of the dynamic
      interplay between interpersonal factors over time is needed.

PMID- 29053984
TI  - Ecological content validation of the Information Assessment Method for parents
      (IAM-parent): A mixed methods study.
AB  - This mixed methods study content validated the Information Assessment Method for
      parents (IAM-parent) that allows users to systematically rate and comment on
      online parenting information. Quantitative data and results: 22,407 IAM ratings
      were collected; of the initial 32 items, descriptive statistics showed that 10
      had low relevance. Qualitative data and results: IAM-based comments were
      collected, and 20 IAM users were interviewed (maximum variation sample); the
      qualitative data analysis assessed the representativeness of IAM items, and
      identified items with problematic wording. Researchers, the program director, and
      Web editors integrated quantitative and qualitative results, which led to a
      shorter and clearer IAM-parent.

PMID- 29053983
TI  - Conceptualizing trust in community-academic research partnerships using concept
      mapping approach: A multi-CTSA study.
AB  - OBJECTIVES: Collaborations between communities, healthcare practices and academic
      institutions are a strategy to address health disparities. Trust is critical in
      the development and maintaining of effective collaborations. The aim of this
      pilot study was to engage stakeholders in defining determinants of trust in
      community academic research partnerships and to develop a framework for measuring
      trust. METHODS: The study was conducted by five collaborating National Institute
      of Health' Clinical and Translational Sciences Awardees. We used concept mapping
      to engage three stakeholders: community members, healthcare providers and
      academicians. We conducted hierarchical cluster analysis to assess the
      determinants of trust in community-academic research partnerships. RESULTS: A
      total of 186 participants provided input generating 2,172 items that were
      consolidated into 125 unique items. A five cluster solution was defined:
      authentic, effective and transparent communication; mutually respectful and
      reciprocal relationships; sustainability; committed partnerships; and,
      communication, credibility and methodology to anticipate and resolve problems.
      CONCLUSION: Results from this study contribute to an increasing empirical body of
      work to better understand and improve the underlying factors that contribute to
      building and sustaining trust in community academic research partnerships.

PMID- 29053985
TI  - Rapid cultivation of free-living planktonic anammox cells.
AB  - Despite that anaerobic ammonium oxidizing (anammox) bacteria are key players in
      the global nitrogen cycle, no pure cultures are still available. Planktonic cell
      culture with high purity is, therefore, essential for physiological and
      biochemical studies of anammox bacteria. However, development of such planktonic
      cell cultures requires an enormous amount of time and effort. Here we developed a
      novel rapid method for cultivating free-living planktonic anammox cells. First,
      anammox granules were physically dispersed, immobilized in 6% polyvinyl alcohol
      4% sodium alginate (PVA-SA) gel beads, and then pre-cultured in an up-flow column
      reactor. Anammox bacteria grew rapidly as loosely flocculated micro-clusters in
      the gel beads. After 18 days of pre-cultivation, mature gel beads were harvested,
      physically dispersed by vortex and inoculated into a membrane bioreactor (MBR).
      The MBR was then continuously operated at a low nitrogen loading rate (<0.9 kg-TN
      m-3 d-1). After 17 days of operation, active free-living planktonic anammox cells
      with purity >95% were successfully developed in the MBR. Total culture time (gel
      beads and MBR) to accomplish free-living planktonic anammox cells was only 35
      days, which was significantly shorter than the previous reports. This new
      cultivation technique could greatly facilitate various microbial, physiological
      and biochemical studies of anammox bacteria.

PMID- 29053986
TI  - Metacognitions in smoking: Evidence from a cross-cultural validation of the
      metacognitions about smoking questionnaire in a Turkish sample.
AB  - Metacognitions about the positive and negative effects of smoking have been
      associated with cigarette use and nicotine dependence. The aim of the present
      study was to validate the Turkish version of the Metacognitions about Smoking
      Questionnaire (MSQ; Nikcevic et al., 2015). The sample consisted of 859 self
      declared smokers (452 female) aged between 18 and 68 years (mean = 28.3; SD =
      7.9). Once the English to Turkish translation of the MDQ was completed,
      confirmatory factor analyses were conducted based on the four-factor structure of
      the original measure. Initially results suggested that this model was an
      inadequate fit of the data obtained. However, by allowing three pairs of items
      (within factor) to co-vary, a re-specified model was tested that was found to be
      a satisfactory fit of the data. Internal reliability and predictive validity of
      the translated scale were observed to be good. The Turkish version of the MSQ
      exhibited suitable psychometric properties. This study also showed that
      metacognitions about smoking predict nicotine dependence independently of
      demographic variables, length of cigarette use, negative affect, and smoking
      outcome expectancies.

PMID- 29053987
TI  - The role of executive functions and psychiatric symptom severity in the Allen
      Cognitive Levels.
AB  - This study examined the relationship between Allen Cognitive Level (ACL) and
      psychiatric symptom severity, level of nursing support required to complete
      activities of daily living (ADLs), and post-hospitalization discharge disposition
      in a sample of 193 acute psychiatric inpatients. A subsample of 31 participants
      with acute psychotic disorders were administered three measures of executive
      functioning in order to examine the convergent validity between ACL and basic
      sequencing and shifting, phonemic fluency, and visuospatial construction.
      Findings indicated significant moderate positive correlations between ACL and
      motor processing speed, basic sequencing and shifting, and phonemic fluency, and
      a nonsignificant relationship with visuospatial construction. A subsample of 166
      participants were administered the Brief Psychiatric Rating Scale-Expanded (BPRS
      E) to assess psychiatric symptom severity. Results indicated a significant weak
      negative correlation between ACL and total psychiatric symptomatology, as well as
      significant weak negative correlations with specific symptoms. In contrast with
      prior research, there was no significant correlation between ACL and level of
      nursing assistance required to complete ADLs. A logistic regression did not
      identify ACL as a contributing factor to post-hospitalization discharge
      disposition. These findings call into question the clinical utility of the ACLS-5
      as an assessment of functional cognition for those experiencing acute psychiatric
      illness.

PMID- 29053988
TI  - Intermedin reduces neointima formation by regulating vascular smooth muscle cell
      phenotype via cAMP/PKA pathway.
AB  - BACKGROUND AND AIMS: Vascular smooth muscle cell (VSMC) dedifferentiation
      contributes to neointima formation, which results in various vascular disorders.
      Intermedin (IMD), a cardiovascular paracrine/autocrine polypeptide, is involved
      in maintaining circulatory homeostasis. However, whether IMD protects against
      neointima formation remains largely unknown. The purpose of this study is to
      investigate the role of IMD in neointima formation and the possible mechanism.
      METHODS: IMD1-53 (100ng/kg/h) or saline water was used on rat carotid-artery
      balloon-injury model. The mouse left common carotid-artery ligation-injury model
      was established using IMD-transgenic and C57BL/6J mice. Immunohistochemistry and
      immunofluorescence staining was used to detect the protein expression in rat
      carotid arteries. Radioimmunoassay was used to determine the serum IMD level. The
      hematoxylin andeosin staining was used for carotid arteries morphological
      testing. In vitro, for rat primary cultured VSMC phenotype transition,
      proliferation and migration assays, platelet-derived growth factor-BB (PDGF-BB)
      reagent and IMD1-53 peptide were added to the culture media at the final
      concentration of 20 ng/mL and 10-7mol/L respectively. Quantification of VSMC
      proliferation involved MTT and BrdU assay and migration was detected by wound
      healing assay. Western blot and realtime PCR were used to detect the protein and
      mRNA levels of tissues or cells. RESULTS: With the rat carotid-artery balloon
      injury model, IMD was significantly downregulated in injured arteries and plasma.
      Exogenous IMD1-53 greatly inhibited neointima formation and prevented VSMC from
      switching to a synthetic phenotype. With the left common carotid-artery ligation
      injury model, IMD-transgenic mice showed less neointima formation than C57BL/6J
      mice. PDGF-BB reduced IMD mRNA expression in rat primary cultured VSMCs but
      increased that of its receptors, calcitonin receptor-like receptor or receptor
      activity-modifying proteins. Furthermore, PDGF-BB promoted VSMC proliferation and
      migration and transformed VSMCs to the synthetic phenotype, which was reversed
      with IMD1-53 treatment. Mechanistically, IMD1-53 maintained the contractile VSMC
      phenotype via the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)
      pathway. CONCLUSIONS: IMD attenuated neointima formation both in the rat model of
      carotid-artery balloon injury and mouse model of common carotid-artery ligation
      injury. IMD protection may be mediated by maintaining a VSMC contractile
      phenotype via the cAMP/PKA pathway.

PMID- 29053989
TI  - Psychometric properties of the Child Anxiety Life Interference Scale - Preschool
      Version.
AB  - Despite growing recognition of childhood anxiety as a common and often
      debilitating clinical concern, we have limited knowledge of the particular ways
      in which anxiety interferes with daily life for young children who have not yet
      entered formal schooling. The present study evaluated the psychometric properties
      of the Child Anxiety Life Interference Scale - Preschool Version (CALIS-PV). The
      CALIS-PV is a brief (18 item) parent-report measure of the impacts of a young
      child's anxiety on their own life and that of her or his parent. Participants
      were 784 parents of a child aged 3-7 years, who completed the CALIS-PV as a part
      of the follow-up assessment battery for two anxiety prevention trials targeted at
      preschool children with temperamental inhibition. Confirmatory factor analysis
      supported three CALIS-PV factors reflecting anxiety-related life interference at
      home, outside home and on parent life. The three factors showed good internal
      consistency and good convergent and divergent validity, and successfully
      differentiated children with and without an anxiety diagnosis. Findings provide
      initial support for the CALIS-PV as a reliable and valid measure of the daily
      life impacts of childhood anxiety for preschool-aged children and their parents.

PMID- 29053990
TI  - Persistence and infectivity of Zika virus in semen after returning from endemic
      areas: Report of 5 cases.
AB  - BACKGROUND: There are limited data about the persistence and infectivity of Zika
      virus in semen of symptomatic travelers returning from endemic areas and even
      less data in asymptomatic cases. OBJECTIVE: We investigated the persistence and
      infectivity of ZIKA virus in semen in five patients with Zika virus infection
      returning to Spain from endemic areas. STUDY DESIGN: We evaluated the
      epidemiological, clinical and virological characteristic of the five patients. In
      semen we detected ZIKA virus by PCR, partial sequencing and cell culture. We also
      performed phylogenetic analysis. RESULTS: We detected Zika virus RNA (Asian
      lineage) by PCR in semen samples from day 14th to day 96th since the day of
      illness onset. Semen viral culture was positive for Zika virus in two patients at
      days of illness 30 and 69 by virus propagation. Phylogenetic analysis strongly
      suggested male to female sexual transmission in a couple returning from Maldives.
      CONCLUSION: This case series confirms that Zika virus RNA can be detected in
      semen up to three months after infection. Viral culture of semen samples shows
      prolonged infectivity that can lead to sexual transmission of Zika virus.

PMID- 29053992
TI  - Biomarker-guided stratification of autoimmune patients for biologic therapy.
AB  - Autoimmunity results from an intersection of genetic and environmental factors
      that cause patient-specific perturbations in immune homeostasis. Defining
      autoimmunity-associated genetic factors has led to mechanistic insight into
      underlying etiologies, and the development of many biologic therapies that target
      the immune system. However, biomarker-informed pairing of patients with optimal
      biologic therapy is lacking. Here, we discuss platforms commonly used to find
      biomarkers that predict response to biologic therapy in autoimmunity and
      highlight recent biomarker discoveries. We also outline how the lack of assay
      standardization is a barrier to successful biomarker validation. Finally, we
      argue that the successful development of companion biomarkers for biologic
      therapy requires collaborative approaches that integrate multiple platforms and
      enable comprehensive measurement of multiple immune pathways.

PMID- 29053991
TI  - Molecular mechanisms of development of the human fetal female reproductive tract.
AB  - Human female reproductive tract development rests mostly upon hematoxilyn and
      eosin stained sections despite recent advances on molecular mechanisms in mouse
      studies. We report application of immunohistochemical methods to explore the
      ontogeny of epithelial and mesenchymal differentiation markers (keratins, homobox
      proteins, steroid receptors), transcription factors and signaling molecules (TP63
      and RUNX1) during human female reproductive tract development. Keratins 6, 7, 8,
      10, 14 and 19 (KRT6, KRT7, KRT8, KRT10, KRT14, KRT19) were expressed in a
      temporally and spatially dynamic fashion. The undifferentiated Mullerian duct and
      uterovaginal canal, lined by simple columnar epithelia, expressed KRT7, KRT8 and
      KRT19. Glandular derivatives of the Mullerian duct (uterine tube, uterine corpus
      and endocervix) maintained expression of these keratins, while tissues that
      undergo stratified squamous differentiation (exocervix and vagina) expressed
      KRT6, KRT14 and KRT10 during development in an age-dependent fashion. TP63 and
      RUNX1 were expressed prior to KRT14, as these two transcription factors are known
      to be upstream from KRT14 in developing Mullerian epithelium. In the vagina,
      KRT10, a marker of terminal differentiation, appeared after endogenous estrogens
      transformed the epithelium to a thick glycogenated squamous epithelium.
      Uroplakin, a protein unique to urothelium, was expressed only in the bladder,
      urethra and vaginal introitus, but not in the female reproductive tract itself.
      Mesenchymal differentiation was examined through immunostaining for HOXA11
      (expressed in uterine mesenchyme) and ISL1 (expressed in vaginal mesenchyme). A
      detailed ontogeny of estrogen receptor alpha (ESR1), progesterone receptor (PGR)
      and the androgen receptor (AR) provides the mechanistic underpinning for the
      teratogenicity of estrogens, progestins and androgens on female reproductive
      tract development. Immunohistochemical analysis of differentiation markers and
      signaling molecules advance our understanding of normal development of the human
      female reproductive tract. These observations demonstrate remarkable similarities
      in mouse and human female reproductive tract development, but also highlight some
      key differences.

PMID- 29053993
TI  - Orexin system in swine ovarian follicles.
AB  - Successful reproduction is strictly linked to metabolic cues. The orexins are a
      family of hypothalamic neurohormones, well known for their key role in the
      control of food intake and the involvement in several aspects of the reproductive
      process. The biological actions of both orexins are carried out through binding
      to the related Orexin 1 (OX1R) and Orexin 2 (OX2R) G-protein-coupled receptors.
      The purpose of this study was to investigate the presence of orexin system
      components in the porcine ovaries, to contribute to expand the knowledge about
      their pleiotropic role. First, we investigated the localization of orexin A (OXA)
      and its receptors by immunochemistry in different ovarian districts. Thereafter,
      we evaluated the expression of the prepro-orexin (PPO) gene and OXA effects on
      granulosa cell functions. Immunohistochemical study revealed the presence of
      orexinergic system components in porcine ovarian follicles. Moreover, our data
      show the expression of PPO messenger RNA in swine ovarian follicles >5 mm. In
      addition, OXA influences proliferation (P < 0.05), steroidogenic activity (P <
      0.05), and redox status of granulosa cells (P < 0.05). Therefore, we hypothesize
      that OXA could exert a local physiological role in swine ovarian follicles even
      if further studies are required to deeply define the function of this pleiotropic
      system.

PMID- 29053995
TI  - Effects of a whey protein supplementation on oxidative stress, body composition
      and glucose metabolism among overweight people affected by diabetes mellitus or
      impaired fasting glucose: A pilot study.
AB  - Obesity and diabetes mellitus type 2 (DM2) are characterized by chronic
      inflammation and oxidative stress [Donath et al. 2013] and this leads to
      cardiovascular diseases [Hulsmans & Holvoet 2010]. Whey proteins (WP) have
      antioxidant [Chitapanarux et al. 2009], anti-inflammatory [Sugawara et al. 2012]
      and hypoglycemic activities [Mignone et al. 2015], while data on weight, body
      composition [Frestedt et al. 2008; Aldrich et al. 2011] and blood pressure are
      conflicting [Kawase et al. 2000; Lee et al. 2007]. WP have unpleasant taste and
      smell [Patel 2015], but a new WP isolate (ProLYOtin(r)) seems to be more
      palatable. 40 g/die of ProLYOtin(r) were supplemented to overweight people (n=31)
      with impaired fasting glucose/DM2 for 12 weeks. Markers of antioxidant status
      (total antioxidant status, glutathione peroxidase, glutathione reductase, uric
      acid), oxidative damage (thiobarbituric acid reactive substances, advanced
      oxidation protein products, 8-hydroxydeoxyguanosine), inflammation (interleukin
      6, high sensitive reactive protein C) and glicemic status (fasting glucose,
      insulin, glycated hemoglobin), anthropometric data (weight, height, waist
      circumference), body composition (body cell mass, fat mass), blood pressure, hand
      grip strength and skin autofluorescence were measured before and at the end of
      supplementation. Isolate palatability was evaluated. An increase in glutathione
      peroxidase, a decrease in uric acid and no change in glutathione reductase, total
      antioxidant status, oxidative damage, inflammation and glucose markers were
      found. Significant improvements in anthropometric parameters and fat mass were
      detected. There wasn't any change in blood pressure, skin autofluorescence and
      physical performance. Two-thirds of subjects judged the supplement positively.
      ProLYOtin(r) seems suitable for treatment of OS and overweight.

PMID- 29053994
TI  - Dietary resveratrol confers apoptotic resistance to oxidative stress in
      myoblasts.
AB  - High levels of reactive oxygen species (ROS) contribute to muscle cell death in
      aging and disuse. We have previously found that resveratrol can reduce oxidative
      stress in response to aging and hindlimb unloading in rodents in vivo, but it was
      not known if resveratrol would protect muscle stem cells during repair or
      regeneration when oxidative stress is high. To test the protective role of
      resveratrol on muscle stem cells directly, we treated the C2C12 mouse myoblast
      cell line with moderate (100 MUM) or very high (1 mM) levels of H2O2 in the
      presence or absence of resveratrol. The p21 promoter activity declined in
      myoblasts in response to high ROS, and this was accompanied a greater nuclear to
      cytoplasmic translocation of p21 in a dose-dependent matter in myoblasts as
      compared to myotubes. Apoptosis, as indicated by TdT-mediated dUTP nick-end
      labeling, was greater in C2C12 myoblasts as compared to myotubes (P<.05) after
      treatment with H2O2. Caspase-9, -8 and -3 activities were elevated significantly
      (P<.05) in myoblasts treated with H2O2. Myoblasts were more susceptible to ROS
      induced oxidative stress than myotubes. We treated C2C12 myoblasts with 50 MUM of
      resveratrol for periods up to 48 h to determine if myoblasts could be rescued
      from high-ROS-induced apoptosis by resveratrol. Resveratrol reduced the apoptotic
      index and significantly reduced the ROS-induced caspase-9, -8 and -3 activity in
      myoblasts. Furthermore, Bcl-2 and the Bax/Bcl-2 ratio were partially rescued in
      myoblasts by resveratrol treatment. Similarly, muscle stem cells isolated from
      mouse skeletal muscles showed reduced Sirt1 protein abundance with H2O2
      treatment, but this could be reversed by resveratrol. Reduced apoptotic
      susceptibility in myoblasts as compared to myotubes to ROS is regulated, at least
      in part, by enhanced p21 promoter activity and nuclear p21 location in myotubes.
      Resveratrol confers further protection against ROS by improving Sirt1 levels and
      increasing antioxidant production, which reduces mitochondrial associated
      apoptotic signaling, and cell death in myoblasts.

PMID- 29053996
TI  - Toxicological and chemical insights into representative source and drinking water
      in eastern China.
AB  - Drinking water safety is continuously threatened by the emergence of numerous
      toxic organic pollutants (TOPs) in environmental waters. In this study, an
      approach integrating in vitro bioassays and chemical analyses was performed to
      explore toxicological profiles of representative source and drinking water from
      waterworks of the Yangtze River (Yz), Taihu Lake (Th), and the Huaihe River (Hh)
      basins in eastern China. Overall, 34 of 96 TOPs were detected in all water
      samples, with higher concentrations in both source and drinking water samples of
      Hh, and pollutant profiles also differed across different river basins. Non
      specific bioassays indicated that source water samples of Hh waterworks showed
      higher genotoxicity and mutagenicity than samples of Yz and Th. An EROD assay
      demonstrated dioxin-like toxicity which was detected in 5 of 7 source water
      samples, with toxin concentration levels ranging from 62.40 to 115.51 picograms
      TCDD equivalents per liter of water (eq./L). PAHs and PCBs were not the main
      contributors to observed dioxin-like toxicity in detected samples. All source
      water samples induced estrogenic activities of 8.00-129.00 nanograms 17beta
      estradiol eq./L, and estrogens, including 17alpha-ethinylestradiol and estriol,
      contributed 40.38-84.15% of the observed activities in examined samples. While
      drinking water treatments efficiently removed TOPs and their toxic effects, and
      estrogenic activity was still observed in drinking water samples of Hh.
      Altogether, this study indicated that the representative source water in eastern
      China, especially that found in Hh, may negatively affect human health, a finding
      that demonstrates an urgent requirement for advanced drinking water treatments.

PMID- 29053997
TI  - Association of polycyclic aromatic hydrocarbons exposure with atherosclerotic
      cardiovascular disease risk: A role of mean platelet volume or club cell
      secretory protein.
AB  - BACKGROUND: Inflammation may play an important role in the association between
      exposure to polycyclic aromatic hydrocarbons (PAHs) and atherosclerotic
      cardiovascular disease (ASCVD) risk. However, the underlying mechanisms remain
      unclear. OBJECTIVES: To investigate the association of PAHs exposure with ASCVD
      risk and effects of mean platelet volume (MPV) or Club cell secretory protein
      (CC16) on the association. METHODS: A total of 2022 subjects (689 men and 1333
      women) were drawn from the baseline Wuhan residents of the Wuhan-Zhuhai Cohort
      study. Data on demography and the physical examination were obtained from each
      participant. Urinary monohydroxy PAH metabolites (OH-PAHs) levels were measured
      by a gas chromatography-mass spectrometry. We estimated the association between
      each OH-PAHs and the 10-year ASCVD risk or coronary heart disease (CHD) risk
      using logistic regression models, and further analyze the mediating effect of MPV
      or plasma CC16 on the association by using structural equation modeling. RESULTS:
      The results of multiple logistic regression models showed that some OH-PAHs were
      positively associated with ASCVD risk but not CHD risk, including 2
      hydroxyfluoren (beta = 1.761; 95% CI: 1.194-2.597), 9-hydroxyfluoren (beta =
      1.470; 95% CI: 1.139-1.898), 1-hydroxyphenanthrene (beta = 1.480; 95% CI: 1.008
      2.175) and SigmaOH-PAHs levels (beta = 1.699; 95% CI: 1.151-2.507). The analysis
      of structural equation modeling shows that increased MPV and increased plasma
      CC16 levels contributed 13.6% and 15.1%, respectively, to the association between
      PAHs exposure and the 10-year ASCVD risk (p < 0.05). CONCLUSIONS: Exposure to
      PAHs may increase the risk of atherosclerosis, which was partially mediated by
      MPV or CC16.

PMID- 29053998
TI  - Effects of ball milling on the physicochemical and sorptive properties of
      biochar: Experimental observations and governing mechanisms.
AB  - With the goal of combining the advantages of ball-milling and biochar
      technologies, a variety of ball-milled biochars (BM-biochars) were synthesized,
      characterized, and tested for nickel (Ni(II)) removal from aqueous solution. Ball
      milling increased only the external surface area of low temperature biochars, but
      still dramatically enhanced their ability to sorb aqueous Ni(II). For higher
      temperature biochars with relatively low surface area, ball milling increased
      both external and internal surface area. Measurements of pH, zeta potential,
      stability, and Boehm titration demonstrated that ball milling also added oxygen
      containing functional groups (e.g., carboxyl, lactonic, and hydroxyl) to
      biochar's surface. With these changed, all the BM-biochars showed much better
      Ni(II) removal efficiency than unmilled biochars. Ball-milled 600  degrees C
      bagasse biochar (BMBG600) showed the greatest Ni(II) adsorption capacity (230-650
      compared to 26-110 mmol/kg for unmilled biochar) and the adsorption was dosage
      and pH dependent. Compared with the unmilled biochar, BMBG600 also displayed
      faster adsorption kinetics, likely due to an increase in rates of intra-particle
      diffusion in the latter. Experimental and modeling results suggest that the
      increase in BM-biochar's external and internal surface areas exposed its
      graphitic structure, thus enhancing Ni(II) adsorption via strong cation-pi
      interaction. In addition, the increase in acidic surface functional groups
      enhanced Ni(II) adsorption by BM-biochar via electrostatic interaction and
      surface complexation. Ball milling thus has great potential to increase the
      efficiency of environmentally friendly biochar for various environmental
      applications.

PMID- 29053999
TI  - Correlations and adsorption mechanisms of aromatic compounds on biochars produced
      from various biomass at 700  degrees C.
AB  - Knowledge of adsorption behavior of organic contaminants on high heat temperature
      treated biochars is essential for application of biochars as adsorbents in
      wastewater treatment and soil remediation. In this study, isotherms of 25
      aromatic compounds adsorption on biochars pyrolyzed at 700  degrees C from
      biomass including wood chips, rice straw, bamboo chips, cellulose, lignin and
      chitin were investigated to establish correlations between adsorption behavior
      and physicochemical properties of biochars. Isotherms were well fitted by Polanyi
      theory-based Dubinin-Ashtakhov (DA) model with three parameters, i.e., adsorption
      capacity (Q0) and adsorption affinity (E and b). Besides the negative correlation
      of Q0 with molecular maximum cross-sectional areas (sigma) of organic compounds,
      positive correlations of Q0 with total pore volume (Vtotal) and average diameter
      of micropore (D) of biochars were observed, indicating that adsorption by
      biochars is captured by the pore-filling mechanism with molecular sieving effect
      in biochar pores. Linear solvation energy relationships (LSERs) of adsorption
      affinity (E) with solvatochromic parameters of organic compounds (i. e., alpham
      and pi*) were established, suggesting that hydrophobic effect, pi-pi interaction
      and hydrogen-bonding interaction are the main forces responsible for adsorption.
      The regression coefficient (pi1) and intercept (C) of obtained LSERs are
      correlated with biochar H/C and Rmicro, respectively, implying that biochars with
      higher aromaticity and more micropores have stronger pi-pi bonding potential and
      hydrophobic effect potential with aromatic molecule, respectively. However,
      hydrogen-bonding potential of biochars for organic molecules is not changed
      significantly with properties of biochars. A negative correlation of b with
      biochar H/C is also obtained. These correlations could be used to predict the
      adsorption behavior of organic compounds on high heat temperature treated
      biochars from various biomass for the application of biochars as sorbents and for
      the estimating of environmental risks of organic compounds in the present of
      biochars.

PMID- 29054000
TI  - When does alcohol hurt? A driving simulator study.
AB  - World-wide, alcohol is still a major cause of traffic accidents. The dose-related
      accident risk function has been found in a large number of risk studies. A
      plethora of laboratory studies has examined the effect of alcohol with regard to
      different information processing capabilities of drivers. Summarizing the
      results, alcohol effects occur at lower blood alcohol concentrations (BAC) the
      more complex the tasks get. However, in contrast, typical alcohol-related crashes
      are frequently single vehicle crashes but not so often crashes in complex
      situations like at intersections. It may be that the subjective assessment of the
      traffic situation and the adaptation of behavior under the influence of alcohol
      plays a major role in accident causation. In order to examine this hypothesis,
      two driving simulator studies were conducted at a target BAC of 0.5g/l comparing
      two (alcohol vs. placebo; n=48, Experiment 1) and three (sober, placebo and
      alcohol; n=63, Experiment 2) groups of subjects in two critical scenarios. The
      first scenario was a seemingly easy traffic situation and was supposed to lead to
      a relaxed driving behavior under alcohol. The second scenario involved a complex
      intersection situation where especially drivers under the influence of alcohol
      should try to concentrate and compensate their experienced alcohol effects. In
      all scenarios, a critical object appeared suddenly and the driver had to react
      fast in order to prevent a (simulated) accident. Overall, the results support the
      hypothesis. Accidents were more frequent for alcohol drivers as compared to
      placebo/sober drivers in the easy scenario, but not the complex one. The initial
      speed of the driver when entering the scenario seems to play a major role in the
      accident causation. Drivers under the influence of alcohol seem to lower their
      speed in complex scenarios, possibly to thus counteract alcohol effects. In
      seemingly easy scenarios this does not seem necessary for them and the arousing
      effect of alcohol may contribute to driving faster. The results are summarized in
      a model of alcohol-related crashes. Further in-depth analyses of real crashes
      would be an interesting next step to further corroborate this model.

PMID- 29054001
TI  - Gate-violation behavior at highway-rail grade crossings and the consequences:
      Using geo-Spatial modeling integrated with path analysis.
AB  - Drivers undertaking risky behaviors at highway-rail grade crossings are often
      severely injured in collisions with trains. Among these behaviors, gate-violation
      (referring to driving around or through the gates that were activated and lowered
      by an approaching train) seems to be one of the most dangerous actions a driver
      might take at a gated crossing; it may compromise the intended safety improvement
      made by adding gates at crossings. This study develops a nuanced conceptual
      framework that uses path analysis to explore the contributing factors to gate
      violation behaviors and the correlation between gate-violation behaviors and the
      crash consequence - the driver injury severity. Further, using geo-spatial
      modeling techniques, this study explores whether the correlates of gate-violation
      behaviors and their associations with injury severity are stationary across
      diverse geographic contexts of the United States. Geo-spatial modeling shows that
      the correlates of gate-violation and its associations with injury severity vary
      substantially across the United States. Spatial variations in correlates of gate
      violation and injury severity are mapped by estimating geographically weighted
      regressions; the maps can serve as an instrument for screening safety
      improvements and help identify regions that need safety improvements. For
      example, the results show that two-quadrant gates are more likely to have gate
      violation crashes than four-quadrant gates in Iowa, Illinois, Wisconsin and
      Minnesota. These states may need to receive more attentions on the enforcement of
      inhibiting gate-violation at crossings with two-quadrant gates or have the
      priority over other states to upgrade these crossings to four-quadrant gates if
      financially feasible.

PMID- 29054002
TI  - Low temperature preparation of oxygen-deficient tin dioxide nanocrystals and a
      role of oxygen vacancy in photocatalytic activity improvement.
AB  - The introduction of oxygen vacancies (Vos) into tin dioxide crystal structure has
      been found as an effective method to improve its photocatalytic performance.
      Herein, oxygen-deficient tin dioxide (SnO2-x) nanocrystals were successfully
      prepared via a facile, one-step hydrothermal method at the temperature lower than
      those reported previously. The effect of hydrothermal temperature on phase
      composition and Vos content was also firstly investigated. Due to its high oxygen
      vacancy concentration, the SnO2-x prepared at 80  degrees C provides the best
      photocatalytic degradation of methyl orange under UV-visible light. Scavenger
      trapping and nitroblue tetrazolium experiments also show that the Vos act as
      electron trapped sites and molecular oxygen adsorption sites, therefore
      increasing the production of active O2- radical which is the main species
      governing the photocatalytic activity of SnO2-x nanocrystals. Raman spectroscopy,
      X-ray photoelectron spectroscopy, photoluminescence measurement and electron spin
      resonance investigation clearly indicate that increasing the hydrothermal
      temperature results in the coexistence of SnO2-x and Sn3O4 phases and the
      reduction of Vos concentration which are detrimental to the photocatalytic
      performance. Density functional theory calculations also reveal that the presence
      of Vos is responsible for the upshift of valence band maximum and an extended
      conduction band minimum, hence a valence band width broadening and band gap
      narrowing which consequently enhance the photocatalytic performance of the oxygen
      deficient SnO2-x.

PMID- 29054003
TI  - Adhesion force sensing and activation of a membrane-bound sensor to activate
      nisin efflux pumps in Staphylococcus aureus under mechanical and chemical
      stresses.
AB  - : Nisin-associated-sensitivity-response-regulator (NsaRS) in Staphylococcus
      aureus is important for its adhesion to surfaces and resistance against
      antibiotics, like nisin. NsaRS consists of an intra-membrane-located sensor NsaS
      and a cytoplasmatically-located response-regulator NsaR, which becomes activated
      upon receiving phosphate groups from the intra-membrane-located sensor.
      HYPOTHESIS: The intra-membrane location of the NsaS sensor leads us to
      hypothesize that the two-component NsaRS system not only senses "chemical"
      (nisin) but also "mechanical" (adhesion) stresses to modulate efflux of
      antibiotics from the cytoplasm. EXPERIMENTS: NsaS sensor and NsaAB efflux pump
      transcript levels in S. aureus SH1000 adhering to surfaces exerting different
      adhesion forces were compared, in presence and absence of nisin. Adhesion forces
      were measured using single-bacterial contact probe atomic force microscopy.
      FINDINGS: Gene expression became largest when staphylococci experienced strong
      adhesion forces combined with nisin-presence and the two-component NsaRS response
      to antibiotics was enhanced at a stronger adhesion force. This confirms that the
      intra-membrane-located sensor NsaS senses both chemical and mechanical stresses
      to modulate antibiotic clearance through the NsaAB efflux pump. This finding
      creates better understanding of the antibiotic resistance of bacteria adhering to
      surfaces and, in the fight against antibiotic-resistant pathogens, may aid
      development of advanced biomaterials on which bacterial efflux pumps are not
      activated.

PMID- 29054004
TI  - Adsorption characteristics of charged and nonionic small molecules to colloidal
      alumina.
AB  - Dense fluorescent pigments used for inkjet printing of UV and IR-readable non
      photobleaching security features require stabilizers to prevent
      aggregation/sedimentation and inkjet head clogging at high resolution. A study of
      small molecule adsorption to alpha-alumina, a model system for security pigments,
      is presented. Alumina is dispersed by two methods yielding different zeta
      potentials but identical isoelectric points. Essentially complete dispersion is
      obtained in water at pH 3 but aggregation occurs at pH 6 where the surface
      charging is lower. Adsorption studies focus on the naphthyl-phosphate, -sulfate,
      and hydroxyl (triethylene glycol) groups. Phosphate adsorption was strongest with
      a 1.2 molecules/nm2 plateau, close to the titratable exchange capacity of 1.3 OH
      groups/nm2 on the alumina surface with DeltaHadsorption=-7.58+/-1.63kJ/mol
      determined by calorimetry. Sulfate adsorption was weaker with a more linear
      adsorption isotherm. The adsorption/exchange process yields a rise in pH that is
      correlated with the binding strength. Hydroxyl binding is weakest, being driven
      by hydrogen bonding, and showed no rise in pH during adsorption. A polyphosphate
      poly(ethylene glycol) block copolymer is expected to be advantageous for the
      dispersion of such inkjet colloids.

PMID- 29054005
TI  - Adsorption of a novel reagent scheme on scheelite and calcite causing an
      effective flotation separation.
AB  - The efficient separation of scheelite from calcium-bearing minerals, especially
      calcite, remains a challenge in practice. In this work, a novel reagent scheme
      incorporating a depressant of sodium hexametaphosphate (SHMP) and a collector
      mixture of octyl hydroxamic acid (HXMA-8) and sodium oleate (NaOl) was employed
      in both single and mixed binary mineral flotation, and it proved to be highly
      effective for the separation. Furthermore, the role of the pH value in the
      separation was evaluated. Additionally, the mechanism of the selective separation
      was investigated systemically via zeta potential measurements, fourier transform
      infrared (FTIR) spectroscopy analysis, X-ray photoelectron (XPS) spectroscopy
      analysis and crystal chemistry calculations. It turns out that the selective
      chemisorption of SHMP on calcite (in the form of complexation between H2PO4
      /HPO42- and Ca2+) over scheelite is ascribed to the stronger reactivity and
      higher density of Ca ions on the commonly exposed surfaces of calcite minerals.
      The intense adsorption of HXMA-8 on scheelite over calcite due to the match of
      the OO distances in WO42- of scheelite and CONHOH of HXMA-8 holds the key to the
      successful separation. We were also interested in warranting the previous claim
      that NaOl is readily adsorbed on both minerals via chemisorption. Our results
      provided valuable insights into the application of mixed collectors and an
      effective depressant for flotation separation.

PMID- 29054006
TI  - Synthesis of hierarchically meso-macroporous TiO2/CdS heterojunction
      photocatalysts with excellent visible-light photocatalytic activity.
AB  - Photocatalysts with a hierarchically porous structure have attracted considerable
      attention owing to their wide pore size distribution and high surface area, which
      enhance the efficiency of transporting species to active sites. In this study,
      hierarchically meso-macroporous TiO2 photocatalysts decorated with highly
      dispersed CdS nanoparticles were synthesized via hydrolysis, followed by a
      hydrothermal treatment. The textural mesopores and interconnected pore framework
      provided more accessible active sites and efficient mass transport for the
      photocatalytic process. The light collection efficiency was enhanced because of
      multiple scattering of incident light in the macropores. Moreover, the formation
      of a heterojunction between the CdS and TiO2 nanoparticles extended the
      photoresponse of TiO2 to the visible-light range and enhanced the charge
      separation efficiency. Therefore, the hierarchically meso-macroporous TiO2/CdS
      photocatalysts exhibited excellent photocatalytic activity for the degradation of
      rhodaming B under visible-light irradiation. Trapping experiments demonstrated
      that superoxide radicals (O2-) and hydroxyl radicals (OH) were the main active
      species in photocatalysis. A reasonable photocatalytic mechanism of TiO2/CdS
      heterojunction photocatalysts was also presented.

PMID- 29054007
TI  - Selective adsorption of tannic acid on calcite and implications for separation of
      fluorite minerals.
AB  - Selective adsorption of tannic acid (TA) on calcite surfaces and the implications
      of this process for the separation of fluorite ore were studied by microflotation
      tests, surface adsorption experiments, zeta potential measurements, UV-vis
      analysis, and X-ray photoelectron spectroscopy (XPS) analysis. The microflotation
      tests indicated that TA, when added before sodium oleate (NaOl), could
      selectively depress calcite from fluorite at pH 7. Surface adsorption experiments
      revealed that TA hinders the interaction of NaOl with calcite. The zeta potential
      of calcite became more negative with TA than with NaOl. However, the
      characteristic features of TA adsorption were not observed on fluorite,
      suggesting that the dominant adsorption sites are dissimilar on the fluorite and
      calcite surfaces in the pulp. UV-vis spectroscopy, XPS, and solution chemistry
      analysis were utilized to obtain a better understanding of the mechanism for
      selective adsorption of TA as well as the key factors determined by the Ca2+ and
      Ca(OH)+ components on the mineral surfaces. A possible adsorption mechanism along
      with an adsorption mode is proposed for the surface interaction between TA and
      calcite.

PMID- 29054008
TI  - Effect of different types of surfactants on the microstructure of
      methyltrimethoxysilane-derived silica aerogels: A combined experimental and
      computational approach.
AB  - HYPOTHESIS: Surfactants interfere with sol-gel particle/pore growth, influencing
      the structure and properties of silica aerogels. Their ability to induce
      microscopic changes in the aerogel's structure may be useful to improve/control
      the thermal insulation performance of aerogels. EXPERIMENTS: The influence of
      different types of surfactants (anionic, cationic and non-ionic) on the
      microstructural arrangement and macroscopic properties of methyltrimethoxysilane
      (MTMS)-based aerogels was evaluated for the first time, using an experimental and
      computational comparative approach. Molecular dynamics simulations were performed
      based on two representative silica molecular structures derived from MTMS, while
      the experimentally-obtained silica aerogels were characterized in terms of
      chemical/structural/mechanical/thermal insulation properties. FINDINGS: The use
      of both hexadecyltrimethylammonium bromide (CTAB) and sodium dodecylsulfate (SDS)
      led to a decrease in bulk density, thermal conductivity and average pore size of
      the aerogels, with notorious increase of their flexibility. The observed changes
      were due to microstructural arrangements, as evidenced by scanning electron
      microscopy (SEM). However, the non-ionic surfactant, Pluronic F-127, did not have
      a positive impact on the desired properties. Globally, the simulation results
      support the experimental findings, suggesting differentiated microstructural
      changes induced by the use of cationic or anionic surfactants. The addition of
      CTAB and SDS generally resulted in smaller or larger silica aggregates,
      respectively.

PMID- 29054009
TI  - Construction of organic-inorganic cadmium sulfide/diethylenetriamine hybrids for
      efficient photocatalytic hydrogen production.
AB  - The design and control of effective, sustainable, cheap, and reusable
      photocatalysts are crucial to the development of solar energy conversion to
      hydrogen (H2) for solving environmental problems. The cadmium
      sulfide/diethylenetriamine (CdS/DETA) hybrid in a single crystalline structure
      was achieved by a solvothermal approach. The organic-inorganic CdS/DETA hybrid
      shows high performance and satisfactory stability for H2 production under visible
      light irradiation. The synergetic chemical coupling effect between CdS and DETA
      leads to a marked increase in the H2 generation rate and the apparent quantum
      yield. H2-production rate of CdS/DETA24 under visible light illumination are
      31.7% and 8059.5MUmolg-1h-1, respectively, which is 3.5 times more than CdS
      nanorods without DETA. Our findings may give a promising method to improve CdS
      for efficient electron-hole separation, electron transferring and anticorrosion
      in photocatalytic process, which reforms the conventional organic-inorganic
      hybrid system.

PMID- 29054010
TI  - The role of water in reducing WO3 film by hydrogen: Controlling the concentration
      of oxygen vacancies and improving the photoelectrochemical performance.
AB  - H2O, as a product of reduced reaction by H2, may affect the chemical equilibrium
      according to the changing of the pressure ratio of H2O/H2 in the system.
      Meanwhile, the performance may also be influenced by adsorption of H2O on the
      surface of the material. In this work, the effect of H2O is studied by reducing
      plate-like array WO3 films under different pressure ratio of H2O/H2. It is
      controlled by changing the water temperature in the washing bottle through which
      the Ar/H2 (80:20) gas flows. The higher water vapor pressure not only decreases
      the content of W5+ but also increases the content of surface hydroxyl groups in
      the WO3 films. Moreover, the excess water vapor improves the crystallinity. The
      WO3 film shows hydrophobicity with adhesive property and high contact angle
      hysteresis after reduction, and the wettability increases with the increase of
      the pressure ratio of H2O/H2. Additionally, a built-in electric field may form by
      dissociation of the surface hydroxyl group and absorption of O- species, which
      promotes the charge separation, showing better photoelectrochemical (PEC)
      performance. Thus, water influences the coverage of chemical species on the
      surface of hydrogen reduced WO3 film, which affects the wettability and PEC
      performance.

PMID- 29054011
TI  - One-pot fabrication of N-doped graphene supported dandelion-like PtRu
      nanocrystals as efficient and robust electrocatalysts towards formic acid
      oxidation.
AB  - Engineering the architectures of metal nanocatalysts offers a valid approach for
      the development of electrocatalysts with greatly enhanced performances. Herein,
      we report the one-pot method to successfully fabricate the N-doped graphene (NG)
      supported dandelion-like PtRu nanocrystals. Such dandelion-like nanocrystals with
      different compositions can be readily tuned via the addition of different amounts
      of RuCl3. By virtue of the large accessible surface active areas, synergistic and
      electronic effect, as well as the successful introduction of NG, the as-obtained
      PtRu/NG with optimized compositions display outstandingly high electrocatalytic
      activity towards formic acid electrooxidation with the mass and specific
      activities of 1857.4mAmg-1 and 18.3mAcm-2, 6.3 and 3.3 times higher than those of
      commercial Pt/C, respectively. Moreover, the Pt1Ru1/NG can endure at least 500
      cycles with less activity decay, showing a new class of Pt-based electrocatalysts
      with enhanced performance for fuel cells and beyond.

PMID- 29054013
TI  - Coagulation factor XIII-A subunit and activation peptide levels in individuals
      with established symptomatic acute deep vein thrombosis.

PMID- 29054012
TI  - The role of long noncoding RNAs in cancer: the dark matter matters.
AB  - Sequencing technology has facilitated a new era of cancer research, especially in
      cancer genomics. Using next-generation sequencing, thousands of long noncoding
      RNAs (lncRNAs) have been identified as abnormally altered in the cancer genome or
      differentially expressed in tumor tissues. These lncRNAs are associated with
      imbalanced gene regulation and aberrant biological processes that contribute to
      malignant transformation. The functions and therapeutic potential of cancer
      related lncRNAs have attracted considerable interest in the past few years.
      Although few lncRNAs have been well-characterized, researchers have recently made
      impressive progress in understanding lncRNAs and their novel functions, such as
      regulation of gene expression, metabolism and DNA repair. These latest findings
      reinforce the crucial roles of lncRNAs in cancer initiation and development, as
      well as their possible clinical applications.

PMID- 29054014
TI  - Sex differences in behavioral and neurochemical effects of gonadectomy and
      aromatase inhibition in rats.
AB  - Aromatase inhibitors, which are widely used for the treatment of estrogen
      dependent cancers, have been associated with psychiatric side effects ranging
      from mania to depression. In the present study, we investigated sex differences
      in the behavioral and neurochemical effects of aromatase inhibition on male and
      female, sham-operated or gonadectomized adult rats. Three weeks after surgery,
      rats received chronic treatment with the aromatase inhibitor letrozole or vehicle
      and were then subjected to the open field test, which assesses general activity.
      Half of the subjects were subsequently exposed to the stressful procedure of the
      forced swim test (FST), which is also a test of antidepressant activity.
      Aromatase activity was analyzed in the hypothalamus and testosterone and
      corticosterone were assayed in the blood serum of all rats. The hippocampus and
      prefrontal cortex (PFC) were analyzed for monoamine (noradrenaline, dopamine and
      serotonin), as well as amino acid (GABA, glutamate, glycine, taurine, alanine and
      histidine) levels. The observed decrease in hypothalamic aromatase activity
      confirmed the efficacy of letrozole treatment in both sexes. Moreover, letrozole
      enhanced testosterone levels in sham-operated females. In the open field test,
      females were overall more active and explorative than males and gonadectomy
      eliminated this sex difference. In the FST, females exhibited overall higher
      immobility than males and gonadectomy further enhanced this passive behavior in
      both sexes. However, sustained aromatase inhibition had no effect on open field
      and FST behaviors. Head shakes during FST, which were fewer in females than in
      males, were reduced by castration in males and by letrozole treatment in
      ovariectomized females, suggesting a role of testosterone and extra-gonadal
      estrogens in the expression of this behavior. Sustained aromatase inhibition also
      decreased noradrenaline and the dopaminergic turnover rates [DOPAC/DA, HVA/DA] in
      the hippocampus and PFC of male and female rats, irrespectively of gonadectomy.
      Moreover, letrozole treatment enhanced the serotonergic turnover [5HIAA/5HT] rate
      in the hippocampus of males and females, irrespectively of gonadectomy. Amino
      acid levels were not influenced by letrozole, but sex differences were
      demonstrated with higher levels in the PFC of females vs. males. Present findings
      suggest that the neuropsychiatric effects of aromatase inhibition can be
      attributed to the inhibition of extragonadal estrogen synthesis, presumably in
      the brain, and could be further associated with serotonergic and
      catecholaminergic changes in brain regions involved in mood and cognition.
      Importantly, present data could be linked with the neurobiology of affective side
      effects in post-menopausal women receiving aromatase inhibitors.

PMID- 29054015
TI  - Synergistic effect of copper and arsenic upon oxidative stress, inflammation and
      autophagy alterations in brain tissues of Gallus gallus.
AB  - Arsenic or copper is one of the most highly toxic pollution that can cause
      dysfunction to brains, however, the exact mechanism remains unclear. The aim of
      the study is to investigate the mechanisms of arsenic or/and copper-induced
      oxidative stress, inflammation and autophagy in chicken brains and elucidate the
      interactions between arsenic and copper. A total of 72 1-day-old Hy-line chickens
      were divided into four groups (18 chickens per group) treated with 30mg/kg
      arsenic trioxide (As2O3) or/and 300mg/kg copper sulfate (CuSO4) for 12weeks.
      Histological signs of inflammation were found in the cerebrum, cerebellum and
      brainstem exposure to arsenic or/and copper. The malondialdehyde (MDA) content
      were up-regulation, whereas oxidative damage parameters total antioxidant
      capacity (T-AOC), glutathione (GSH), the inhibition ability of hydroxyl radical
      (OH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GPx) were significantly decreased (P<0.05). The mRNA levels and protein
      expressions of inflammation markers, such as nuclear factor kappa B (NF-kappaB),
      tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2) and
      prostaglandin E synthase (PTGEs) were significantly increased (P<0.05). The mRNA
      levels and protein expressions of autophagy markers including
      phosphatidylinositol 3-kinase (PI3K), Akt, autophagy-related gene 5 (ATG5),
      microtubule-associated protein light chains 3 (LC3), ATG4B, and Becline1 in
      different regions of brains were up-regulation (P<0.05), except the mammalian
      target of rapamycin complex (mTORC). In conclusion, we speculated that arsenic or
      copper could induce oxidative stress, inflammation and autophagy in chicken
      brains, and there may have a synergistic effect between copper and arsenic.

PMID- 29054016
TI  - Job burnout predicts decline of health-related quality of life among employees
      with cardiovascular disease: A one-year follow-up study in female nurses.
AB  - OBJECTIVE: To examine whether job burnout is associated with health-related
      quality of life (HRQOL) in employees with cardiovascular disease. METHODS: In
      this longitudinal study, we included 305 female hospital nurses with
      cardiovascular disease. Job burnout was measured by the 6-item Copenhagen Burnout
      Inventory at baseline. We categorized study participants into low, intermediate
      and high levels of job burnout based on tertiles. HRQOL at baseline and at one
      year follow-up was operationalized in terms of the physical and mental
      functioning summary scores of the short form 8-item health survey (SF-8), which
      is an abbreviated version of the widely used SF-36 with score ranges of 0-100.
      Linear regression was applied to examine longitudinal associations. RESULTS:
      After taking into account relevant socio-demographic, behavioral, and work
      related covariates as well as HRQOL scores at baseline, we found that both
      physical functioning and mental functioning declined (by 2.53 points and 3.02
      points respectively, p<0.05) in the high job burnout group compared with the low
      job burnout group. Dose-response relationships were also observed (p<0.05).
      CONCLUSION: Job burnout predicts decline of HRQOL one year later among employees
      with cardiovascular disease.

PMID- 29054018
TI  - Isolated aphasia in the emergency department: The likelihood of ischemia is low.
AB  - OBJECTIVE: Aphasia is a common presentation of ischemic stroke, often diagnosed
      in the acute setting using tools such as the NIH Stroke Scale (NIHSS). Due to the
      vascular distribution of the middle cerebral artery, it is often accompanied by
      other symptoms such as weakness, sensory loss, or visual changes. Isolated
      aphasia due to ischemia is possible, but language problems mimicking aphasia
      syndromes can also be seen with other diagnoses such as metabolic abnormalities
      or dementia. In this study, we determine the incidence of aphasia-only strokes
      using the NIHSS, and factors associated with a higher likelihood of ischemia.
      PATIENTS AND METHODS: Over a 2year period, 788 patients presented to our
      Emergency Department with symptoms of acute stroke. Data were collected regarding
      patient demographics, medical history, presenting symptoms (based on NIHSS), work
      up results, and final diagnosis. The incidence of aphasia-only stroke was
      calculated. Student's t-tests and chi square analysis were used to determine
      factors associated with ischemia. RESULTS: Of 788 patients, 21 (3%) presented
      with isolated "aphasia". None of the 21 had infarcts on neuroimaging. Three (14%)
      were diagnosed with possible transient ischemic attacks and the rest with stroke
      mimics. Toxic/metabolic disturbances were the most common mimics (39%). Prior
      history of stroke or transient ischemic attack was associated with ischemia over
      mimic (p=0.023). CONCLUSIONS: Strokes affecting language without motor or sensory
      deficits are uncommon. In the acute setting, isolated "aphasia" is most often due
      to a stroke mimic; however can occur rarely, particularly in those with prior
      history of ischemia.

PMID- 29054017
TI  - Hyperventilation and electroconvulsive therapy: A literature review.
AB  - BACKGROUND: Hyperventilation has been proposed as an augmentation strategy in
      electroconvulsive therapy (ECT) in accordance with its proconvulsant effect.
      OBJECTIVE: This study reviews the existing literature on the application of
      hyperventilation in ECT, its efficacy, and tolerance. METHODS: A systematic
      search was performed in PubMed and EMBASE databases. Search terms
      ('electroconvulsive therapy' and 'hyperventilation', 'ventilation',
      'hyperoxygenation', 'hyperoxia', 'hypocapnia') were used to retrieve works from
      1966 to June 2016. Works that described hyperventilation manoeuvres in ECT
      settings and their clinical repercussion were included in the review. RESULTS: A
      total of 17 observational and experimental studies were selected. An important
      heterogeneity in study designs, samples and ECT conditions, was detected.
      Findings support a positive influence of hyperventilation on seizure duration,
      which is the main study variable across different works. Effects of
      hyperventilation on seizure threshold and quality parameters have been less
      thoroughly studied. Systematic recording of clinical outcomes and adverse effects
      of hyperventilation is uncommon. CONCLUSIONS: The literature suggests that
      hyperventilation may be an effective and safe technique to enhance ECT, but many
      aspects remain to be studied. Further investigations, especially controlled
      clinical trials, are necessary and should result in a specific and reliable
      hyperventilation protocol for ECT settings.

PMID- 29054019
TI  - Emergency preparedness for the accidental release of radionuclides from the Uljin
      Nuclear Power Plant in Korea.
AB  - Site specific radionuclide dispersion databases were archived for the emergency
      response to the hypothetical releases of 137Cs from the Uljin nuclear power plant
      in Korea. These databases were obtained with the horizontal resolution of 1.5 km
      in the local domain centered the power plant site by simulations of the
      Lagrangian Particle Dispersion Model (LPDM) with the Unified Model (UM)-Local
      Data Assimilation Prediction System (LDAPS). The Eulerian Dispersion Model-East
      Asia (EDM-EA) with the UM-Global Data Assimilation Prediction System (UM-GDAPS)
      meteorological models was used to get dispersion databases in the regional
      domain. The LPDM model was performed for a year with a 5-day interval yielding 72
      synoptic time-scale cases in a year. For each case hourly mean near surface
      concentrations, hourly mean column integrated concentrations, hourly total
      depositions for 5 consecutive days were archived by the LPDM model in the local
      domain and by the EDM-EA model in the regional domain of Asia. Among 72 synoptic
      cases in a year the worst synoptic case that showed the highest mean surface
      concentration averaged for 5 days in the LPDM model domain was chosen to
      illustrate the emergency preparedness to the hypothetical accident at the site.
      The simulated results by the LPDM model with the 137Cs emission rate of the
      Fukushima nuclear power plant accident for the first 5-day period were found to
      be able to provide prerequisite information for the emergency response to the
      early phase of the accident whereas those of the EDM-EA model could provide
      information required for the environmental impact assessment of the accident in
      the regional domain. The archived site-specific database of 72 synoptic cases in
      a year could have a great potential to be used as a prognostic information on the
      emergency preparedness for the early phase of accident.

PMID- 29054020
TI  - Unraveling the mechanisms behind iron overload and ineffective hematopoiesis in
      myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a group of clonally-acquired blood disorders
      characterized by ineffective hematopoiesis leading to cytopenias. Red blood cell
      transfusions are an important component of supportive care in patients with MDS.
      Prolonged exposure to transfusions can lead to iron overload, which results in
      iron-induced toxicity caused by the production of reactive oxygen species (ROS).
      ROS accumulation has detrimental effects also on hematopoietic stem cells and may
      contribute to MDS progression. The observation that iron chelation improves
      hematologic parameters and reduces transfusion dependence further indicates that
      iron overload impairs hematopoiesis. Over the past decade, the mechanisms
      regulating iron homeostasis and the complex interplay between iron overload and
      toxicity, ineffective hematopoiesis, and transformation to leukemia have become
      clearer. In this narrative review, we provide an overview of recent findings
      pertaining to iron overload in patients with MDS and its effects on
      hematopoiesis. We also briefly discuss the position of chelation therapy in the
      context of the new developments.

PMID- 29054021
TI  - QPRTase modified N-doped carbon quantum dots: A fluorescent bioprobe for
      selective detection of neurotoxin quinolinic acid in human serum.
AB  - Highly fluorescent nitrogen doped carbon quantum dots (NCQDs) were synthesized
      using microwave assisted green method. It was characterized by Transmission
      Electron Microscopy (TEM), FTIR, UV-Visible absorption and Photoluminiscence (PL)
      techniques. The NCQDs were immobilized with an enzyme named quinolinate
      phoshphoribosyl transferase (QPRTase). The NCQDs immobilized by QPRTase was used
      as a fluorescent bioprobe for the selective detection of endogenous neurotoxin
      quinolinic acid (QA) whose elevated level in serum is marker of many neurological
      disorders such as Alzheimer's, Huntington's and HIV associated dementia (HAD) as
      well as deficiency of vitamin B6. Steady state PL studies were carried out to
      measure the PL response of the fabricated fluorescent bioprobe as a function of
      QA concentrations in human serum samples. This probe was found applicable in
      linear range [3.22-51uM] with the limit of detection ~ 6.51uM. It has desirable
      sensitivity ~ (0.02340+/-0.0001) uM-1, excellent stability for ~ 7 weeks and good
      reproducibility. The similar response of this fluorescent bioprobe for QA
      detection in triple distilled water and human serum shows that it is unaffected
      by variation in media. Hence, this fluorescent bioprobe can be employed for QA
      detection in serum sample for the early detection of many diseases.

PMID- 29054022
TI  - A shape-code nanoplasmonic biosensor for multiplex detection of Alzheimer's
      disease biomarkers.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease associated with the loss
      of nerve cells in the brain. The disease is affected by multifactorial pathways
      and leads to changes in related biomolecular levels as AD progresses. Therefore,
      AD should be diagnosed with combined detection of several lesions to improve
      accuracy. Amyloid beta 1-40, 1-42 and tau (tau) protein are milestones in AD
      pathology and can be used as main screening and diagnostic target markers. Here,
      we suggest a highly selective biosensor for detection of AD core biomarkers on
      one platform through distinct localized surface plasmon resonance (LSPR)
      depending on gold nanoparticles shapes, called a shape-code biosensor. This
      plasmonic sensor consists of only gold nanoparticles and antibody, but does not
      need additory methods for precise separation from multifarious samples and
      identification of markers. Under physiological condition, we determined a
      detection limit of 34.9fM for amyloid beta (Abeta) 1-40, 26fM for Abeta 1-42 and
      23.6fM for tau protein corresponding to the ~ 1, ~ 2.23 and ~ 3.12nm of Rayleigh
      scattering peak shift on shape-code plasmon system for each biomarker in mimicked
      blood. This is the first highly sensitive shape-code biosensor to detect AD
      biomarkers which can be used to diagnose AD easily in the future.

PMID- 29054023
TI  - Charting the territory: Describing the functional abilities of children with
      progressive neurological conditions.
AB  - AIMS: Little is known about the functional abilities of children with progressive
      genetic, metabolic, or neurological conditions (PNCs). In this study, children
      with PNCs were followed over a 2-year period to assess their functional abilities
      over time. Specific aims were to: 1) describe the changes in functional skills
      and the effects of age for children with PNCs, 2) assess changes in these
      children's need for caregiver assistance over time, and 3) examine relationships
      between these children's functional skills and need for caregiver assistance.
      METHODS: This study involved a longitudinal, descriptive design with three
      assessments occurring at Baseline, Year 1, Year 2. Functional skills and
      caregiver assistance were assessed by the Pediatric Evaluation of Disability
      Inventory (PEDI). The PEDI questionnaire was completed at baseline and then
      yearly by parents, along with the assistance of a trained research assistant
      (RA). RESULTS: The study was completed with 83 children (mean age at
      Baseline=7.1yrs, SD=4.6). Mean Functional skills scores were in the low ranges at
      Baseline and did not change significantly across time points (F(2, 71)=0.437,
      p=0.58). Time point had no effect on caregiver assistance ratings (p<0.2);
      however, children required greater amounts of help with self-care at later time
      points than for other functional domains. Statistically significant correlations
      were found between PEDI-Functional skills and caregiver assistance ratings
      (r=0.80-0.90, p<0.01). CONCLUSIONS: Functional skills were low for these children
      overall, irrespective of age. In children with PNCs: 1) mean functional skills
      did not change significantly over time; 2) caregiver assistance scores remained
      stable and 3) functional skills and levels of caregiver assistance were strongly
      positively correlated. Further research to explore the long-term functional
      trajectory in children with a PNC is recommended.

PMID- 29054024
TI  - Social skills plus relaxation training with a child with ASD in the schools.
AB  - A social skills plus relaxation training (SSRT) program was developed using
      direct training, relaxation training, and reinforcement principles. The aim was
      to examine the effectiveness of SSRT on increasing the frequency of three target
      behaviors for one 8-year-old, student classified with autism spectrum disorder
      (ASD). A multiple-baseline across behaviors design was used to evaluate the
      effects of SSRT. During baseline, intervention, and maintenance sessions the
      student's responses were videotaped and then subsequently viewed and coded after
      the session. During intervention, the student's correct responses for the
      targeted social skills increased and were maintained 17 weeks after SSRT ended.
      This study adds support for the use of this SSRT program in a school setting with
      children who have ASD.

PMID- 29054025
TI  - Antibacterial activity against cariogenic bacteria and cytotoxic and genotoxic
      potential of Anacardium occidentale L. and Anadenanthera macrocarpa (Benth.)
      Brenan extracts.
AB  - OBJECTIVES: The present study aimed to assess the antibacterial activity against
      bacteria with cariogenic relevance, toxic and genotoxic potential of the plants
      Anacardium occidentale L. and Anadenanthera macrocarpa (Benth.) Bernam. DESIGN:
      Using a microdilution technique, the extracts were submitted to minimum
      inhibitory concentration (MIC) testing against Streptococcus mitis (ATCC 903),
      Streptococcus mutans (ATCC 25175), Streptococcus oralis (ATCC 10557),
      Streptococcus salivarius (ATCC 7073), Streptococcus sanguinis (ATCC 15300) and
      Streptococcus sobrinus (ATCC 27609). The toxicity of the extracts was then
      verified against eukaryotic cells. Additionally, a micronucleus assay was
      performed to investigate the potential mutagenic effects of the extracts on rat
      erythrocytes. The Student's t-test, Bonferroni test, and one-way ANOVA followed
      by Tukey's tests were used for statistical analysis, at a significance level of
      5%. RESULTS: While the A. occidentale extract was able to inhibit all of the
      tested strains, with S. mutans and S. mitis being the most susceptible to that
      extracts action, the A. macrocarpa did not show antimicrobial activity.
      Interestingly, the hemolytic, oxidant and antioxidant activities were slightly
      observed for either extract, even at high concentrations (1000mg/mL). The
      micronucleus assay showed no significant changes in the cells exposed to the
      extracts. CONCLUSION: The A. occidentale extract has potential as an
      antimicrobial agent with low eukaryotic cell toxicity or mutagenic activity. The
      A. macrocarpa extract, although absent of antibacterial activity might as well be
      a safe and effective phytotherapeutic alternative.

PMID- 29054026
TI  - Intelligent tuning method of PID parameters based on iterative learning control
      for atomic force microscopy.
AB  - Proportional-integral-derivative (PID) parameters play a vital role in the
      imaging process of an atomic force microscope (AFM). Traditional parameter tuning
      methods require a lot of manpower and it is difficult to set PID parameters in
      unattended working environments. In this manuscript, an intelligent tuning method
      of PID parameters based on iterative learning control is proposed to self-adjust
      PID parameters of the AFM according to the sample topography. This method gets
      enough information about the output signals of PID controller and tracking error,
      which will be used to calculate the proper PID parameters, by repeated line
      scanning until convergence before normal scanning to learn the topography.
      Subsequently, the appropriate PID parameters are obtained by fitting method and
      then applied to the normal scanning process. The feasibility of the method is
      demonstrated by the convergence analysis. Simulations and experimental results
      indicate that the proposed method can intelligently tune PID parameters of the
      AFM for imaging different topographies and thus achieve good tracking
      performance.

PMID- 29054027
TI  - Sapofectosid - Ensuring non-toxic and effective DNA and RNA delivery.
AB  - Different methods are being deployed for non-viral DNA/RNA delivery. However non
      viral formulations for DNA/RNA-delivery are often accompanied by severe toxicity
      and thus low efficiency. Particular costly cell culture media are required as
      well. Here we introduce sapofection as a valuable enhancing method for non-viral
      DNA/RNA delivery. Sapofection is based on the application of DNA/RNA nanoplexes
      and sapofectosid, a plant derived natural transfection reagent. Sapofectosid was
      produced from plant raw material by chromatographic methods and characterized by
      tandem mass spectrometry and intensive one and two dimensional NMR-spectroscopy.
      Sapofectosid did enhance the transfection efficiency of different DNA- and RNA
      nanoplexes formulated with liposomes, polyethylenimine (PEI) or targeted and non
      targeted oligo-lysine peptides. All nanoplexes were characterized
      physicochemically and the influence of sapofectosid on the nanoplex integrity was
      determined by DNA complexation assays. The nanoplexes and sapofectosid were
      administered to a variety of cancer cell lines and the transfection efficiency
      was investigated by flow cytometry and confocal microscopy. Dependent on the cell
      line the transfection efficiencies varied from 6 to 76%. The saponin- and
      receptor-mediated endocytosis of nanoplexes was investigated by flow cytometry.
      As demonstrated by impedance based live cell imaging sapofection was non-toxic.
      The findings show the great potential of sapofection to be used as an effective
      and non-toxic transfection enhancing method.

PMID- 29054028
TI  - Impact of fomesafen on the soil microbial communities in soybean fields in
      Northeastern China.
AB  - Fomesafen, a widely adopted residual herbicide, is used throughout the soybean
      region of northern China for the spring planting. However, the ecological risks
      of using fomesafen in soil remain unknown. The aim of this work was to evaluate
      the impact of fomesafen on the microbial community structure of soil using
      laboratory and field experiments. Under laboratory conditions, the application of
      fomesafen at concentrations of 3.75 and 37.5mg/kg decreased the basal respiration
      (RB) and microbial biomass carbon (MBC). In contrast, treatment with 375mg/kg of
      fomesafen resulted in a significant decrease in the RB, MBC, abundance of both
      Gram+ and Gram- bacteria, and fungal biomass. Analysis of variance showed that
      the treatment accounted for most of the variance (38.3%) observed in the soil
      microbial communities. Furthermore, the field experiment showed that long-term
      fomesafen application in continuously cropped soybean fields affected the soil
      bacterial community composition by increasing the relative average abundance of
      Proteobacteria and Actinobacteria species and decreasing the abundance of
      Verrucomicrobia species. In addition, Acidobacteria and Chloroflexi species
      showed a pattern of activation-inhibition. Taken together, our results suggest
      that the application of fomesafen can affect the community structure of soil
      bacteria in the spring planting soybean region of northern China.

PMID- 29054029
TI  - Endocranial illuminator: A technique for transilluminating the skull.
AB  - A novel tool, the endocranial illuminator (EI), has been devised to facilitate
      examination of the interior of the intact human cranium. A number of the
      endocranial characteristics including cranial thickness, sutural complexities,
      and foramina are easy visible with this device. The EI enhances the accuracy of
      anatomical examination of the cranial vault in forensic, archaeological, and
      historical crania in those cases where they must remain intact. The EI is simple
      and inexpensive to construct and lightweight so it can be used in the laboratory
      or easily transported in the field.

PMID- 29054030
TI  - Measurement of strain and tensile force of the supraspinatus tendon under
      conditions that simulates low angle isometric elevation of the gleno-humeral
      joint: Influence of adduction torque and joint positioning.
AB  - BACKGROUND: Recently, supraspinatus muscle exercise has been reported to treat
      rotator cuff disease and to recover shoulder function. However, there have been
      no report on the direct measurement of strain on the supraspinatus tendon during
      simulated isometric gleno-humeral joint elevation. METHODS: Ten fresh-frozen
      shoulder specimens with the rotator cuff complex left intact were used as
      experimental models. Isometric gleno-humeral joint elevation in a sitting
      position was reproduced with low angle of step-by-step elevation in the scapular
      plane and strain was measured on the surface layer of the supraspinatus tendon.
      FINDINGS: In isometric conditions, applied tensile force of the supraspinatus
      tendon increased significantly with increases in adduction torque on the gleno
      humeral joint. Significant increases in the strain on the layer were observed by
      increase in adduction torque, which were recorded in isometric elevation at -10
      degrees  and 0 degrees , but little increase in the strain was observed at 10
      degrees  or greater gleno-humeral elevation. INTERPRETATION: Increased strain on
      the surface layer of the supraspinatus tendon was observed during isometric gleno
      humeral elevation from -10 to 0 degrees . These findings demonstrate a potential
      risk of inducing overstretching of the supraspinatus tendon during supraspinatus
      muscle exercise.

PMID- 29054031
TI  - Mental health of heroin users with differing injection drug use histories: A non
      treatment sample of Mexican American young adult men.
AB  - BACKGROUND: While the comorbidity of mental health and injecting heroin has been
      documented, current research is limited by describing the mental health of people
      who inject drugs without a comparison group and by the lack of research on
      nontreatment samples in the United States, particularly among Hispanics. The
      purpose of this study was to examine the association of injecting history (never,
      former, occasional, and daily) and multiple outcomes of global and mental health
      using a sample of U.S.-based Latinos not currently in treatment. METHODS: Data
      are from a sample of street-recruited Mexican American young adult men (n=275) in
      San Antonio, TX. Multiple logistic regression and structural equation modeling
      were used. RESULTS: Overall 54% of men reported lifetime injecting drug use
      (20.7% former users, 11.1% occasional users, and 21.9% daily users). We found
      varying prevalence rates of global and mental health status among different
      histories of injecting. After covariate adjustment, daily injecting remained
      strongly associated with all four outcomes: perceived poor health status
      (AOR=4.39; p<=0.001), psychological distress (AOR=2.78; p<=0.05), depression
      (AOR=4.37; p<=0.001), and suicidal ideation (OR=4.75; p<=0.001). Acculturation,
      gang membership, and incarceration history also emerged as important factors.
      CONCLUSION: This study provides new information about the relationship between
      mental health and injecting heroin use. FINDINGS: Support the need to consider
      mental health states among people who inject drugs, and to examine varying
      histories of injecting with socially and culturally relevant factors.

PMID- 29054032
TI  - Constipation and other common symptoms reported by women and men in methadone and
      buprenorphine maintenance treatment.
AB  - BACKGROUND: Opioid substitution treatment (OST) is often continued long-term and,
      therefore, opioid-associated symptoms are of interest. Symptoms associated with
      methadone maintenance treatment (MMT) in men are well described, but there are
      fewer reports concerning symptoms associated with buprenorphine maintenance
      treatment (BMT) and very few reports among women. METHOD: Recipients of BMT
      (n=113) and MMT (n=184), non-opioid users (n=105) and opioid users not receiving
      OST (n=87) completed the Patient Assessment of Constipation (PAC-SYM) and a
      general symptom checklist. Multivariate analysis included other potential
      moderators of opioid-associated symptoms. FINDINGS: Opioid users reported a
      higher frequency and severity of symptoms than non-opioid users. Constipation,
      dry mouth, decreased appetite, sweating and fatigue were highly prevalent in the
      previous 30days (51-80%). Nausea, itchy skin, trouble urinating, menstrual
      problems, lightheadedness, blurred vision, heart racing were also common (30
      50%). Non-OST opioid users had significantly higher frequency and severity than
      OST recipients of nausea, vomiting, diarrhoea, decreased appetite, sweating and
      itchy skin. Sweating was significantly more common in MMT than BMT. Constipation
      scores were higher in women, otherwise most sex differences were small. Higher
      PAC-SYM scores were associated with vomiting (OR=1.04) and sweating (OR=1.06).
      Cannabis use was associated with vomiting (OR=2.19). Constipation (OR=1.07),
      insomnia (OR=2.5) and depression (OR=2.82) were associated with fatigue.
      CONCLUSION: Men and women receiving OST report similarly high rates of somatic
      symptoms, though less than opioid users not receiving OST. There were few
      differences between BMT and MMT. Buprenorphine might be preferred where sweating
      is problematic. Several modifiable factors were identified.

PMID- 29054033
TI  - Hepatitis C antibody prevalence among Mexico City prisoners injecting legal and
      illegal substances.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among prisoners
      and this prevalence estimates reach 64% among prisoners who inject illicit drugs.
      Prisons are important sites for HCV transmission in the absence of access to
      sterile injecting equipment; hence, it can be transmitted between prisoners who
      share contaminated needles and syringes. We aimed to estimate the prevalence of
      risk factors for anti-HCV prevalence, with particular interest on injecting
      behavior, and to assess correlates of anti-HCV positivity among Mexico City
      prisoners. METHODS: Cross-sectional study based on information -collected in
      three male and two female prisons in Mexico City during 2010-2011- about sexually
      transmitted infections, socio-demographics, criminal history, substance use,
      vitamin injection, tattooing, among others (n=3,910). Weighted multivariable
      adjusted logistic regression models were estimated to assess the overall and
      differential odds for anti-HCV due to injecting behavior. RESULTS: Overall
      prevalence of anti-HCV was 3.3%. This figure rose to 43.1% among prisoners with a
      history of illicit drug injection. Prisoners with history of vitamin injection
      showed a similar prevalence of anti-HCV (43.8%). After stratifying by substance
      injected, the adjusted odds ratio was 9.8 (95% CI: 4.0, 23.8) for illicit drug
      injection and 11.9 (95% CI: 5.8, 23.8) for illicit drug and vitamin injection.
      CONCLUSION: Based on data from the most populous prisons in Mexico City, this
      study showed that anti-HCV is highly prevalent among prisoners with history of
      injecting behavior. In this sense, injecting behavior per-se, independent of the
      substance used, is associated with increased odds of anti-HCV positivity.

PMID- 29054034
TI  - An exploration of common dopaminergic variants and behavior problems in siblings
      at high risk for autism spectrum disorder.
AB  - Younger siblings of children with ASD often exhibit elevated internalizing and
      externalizing problems. We investigated common dopaminergic variants (DRD4 and
      DRD2) in relation to behavior problems at 36 months. Genotypes linked to less
      efficient dopaminergic functioning were associated with higher internalizing
      problems in high-risk siblings.

PMID- 29054035
TI  - Combining near infrared spectroscopy with predictive model and expertise to
      monitor herb extraction processes.
AB  - Albeit extensively utilized, herb extraction process (HEP) is hard to be
      monitored because of its batch nature and the fluctuating quality of raw
      materials. Process analytical tools like near infrared spectroscopy (NIRS) can
      offer nondestructive examinations and collect abundant data of the process, which
      in principle contain the information about the quality of both the product and
      the process itself. However, extra effort is often required for the data mining
      of such process measurements, and extracting knowledge of the quality of process
      can be even harder. In this study, we take the extraction process of licorice as
      a typical HEP instance, and combine NIRS with classical partial least squared
      regression (PLSR) and expertise for its on-line monitoring. We show that our
      scheme effectively extracts information with clear physical meanings, through
      which we can even uncover the process fault that does not induce evident
      abnormalities in the product quality. Moreover, the constructed model can
      continuously evolve with more process data from daily operations, and the idea of
      the whole framework can be directly generalized to other HEP.

PMID- 29054036
TI  - SNAVA-A real-time multi-FPGA multi-model spiking neural network simulation
      architecture.
AB  - Spiking Neural Networks (SNN) for Versatile Applications (SNAVA) simulation
      platform is a scalable and programmable parallel architecture that supports real
      time, large-scale, multi-model SNN computation. This parallel architecture is
      implemented in modern Field-Programmable Gate Arrays (FPGAs) devices to provide
      high performance execution and flexibility to support large-scale SNN models.
      Flexibility is defined in terms of programmability, which allows easy synapse and
      neuron implementation. This has been achieved by using a special-purpose
      Processing Elements (PEs) for computing SNNs, and analyzing and customizing the
      instruction set according to the processing needs to achieve maximum performance
      with minimum resources. The parallel architecture is interfaced with customized
      Graphical User Interfaces (GUIs) to configure the SNN's connectivity, to compile
      the neuron-synapse model and to monitor SNN's activity. Our contribution intends
      to provide a tool that allows to prototype SNNs faster than on CPU/GPU
      architectures but significantly cheaper than fabricating a customized
      neuromorphic chip. This could be potentially valuable to the computational
      neuroscience and neuromorphic engineering communities.

PMID- 29054037
TI  - Director Field Analysis (DFA): Exploring Local White Matter Geometric Structure
      in Diffusion MRI.
AB  - In Diffusion Tensor Imaging (DTI) or High Angular Resolution Diffusion Imaging
      (HARDI), a tensor field or a spherical function field (e.g., an orientation
      distribution function field), can be estimated from measured diffusion weighted
      images. In this paper, inspired by the microscopic theoretical treatment of
      phases in liquid crystals, we introduce a novel mathematical framework, called
      Director Field Analysis (DFA), to study local geometric structural information of
      white matter based on the reconstructed tensor field or spherical function field:
      (1) We propose a set of mathematical tools to process general director data,
      which consists of dyadic tensors that have orientations but no direction. (2) We
      propose Orientational Order (OO) and Orientational Dispersion (OD) indices to
      describe the degree of alignment and dispersion of a spherical function in a
      single voxel or in a region, respectively; (3) We also show how to construct a
      local orthogonal coordinate frame in each voxel exhibiting anisotropic diffusion;
      (4) Finally, we define three indices to describe three types of orientational
      distortion (splay, bend, and twist) in a local spatial neighborhood, and a total
      distortion index to describe distortions of all three types. To our knowledge,
      this is the first work to quantitatively describe orientational distortion
      (splay, bend, and twist) in general spherical function fields from DTI or HARDI
      data. The proposed DFA and its related mathematical tools can be used to process
      not only diffusion MRI data but also general director field data, and the
      proposed scalar indices are useful for detecting local geometric changes of white
      matter for voxel-based or tract-based analysis in both DTI and HARDI
      acquisitions. The related codes and a tutorial for DFA will be released in
      DMRITool.

PMID- 29054038
TI  - Epileptic headache: A rare form of painful seizure.
AB  - PURPOSE: To describe the concept, features and mechanisms of epileptic headache
      (EH). METHODS: Analysis of all published articles concerning EH and related
      subjects. RESULTS: There are more than 30 published case studies of patients with
      headache as the only manifestation of a seizure, a condition that has been
      variously called "EH", "ictal epileptic headache", "hemicrania epileptica",
      "cephalic pain seizure". It is necessary to differentiate EH from "migralepsy"
      and "ictal non-epileptic headache". EH may be an isolated event or the initial
      phase of a seizure followed by other manifestations. An isolated EH is clinically
      relevant because it is often symptomatic of structural brain disease; this
      underlines the importance of a differential diagnosis as the head pain of EH has
      no specific diagnostic characteristics. The described cases indicate that the
      location of the foci may vary, thus suggesting the involvement of different parts
      of the pain network. EH is a "focal aware" seizure, but there are a few reports
      of cases in which it was associated with generalised epileptiform activity. A
      correct diagnosis of EH requires an ictal EEG recording showing epilepsy
      compatible discharges that coincide with the onset and cessation of the headache.
      A rapid response to the acute administration of an antiepileptic drug may support
      the diagnosis. CONCLUSIONS: EH is a particular type of pain seizure that has a
      complex pathophysiology and, when isolated, requires differential diagnostic
      consideration. We believe that, although it is not frequent, pain as an ictal
      symptom should be highlighted in the operational classification of seizure types.

PMID- 29054039
TI  - Control of brain energy supply by astrocytes.
AB  - Astrocytes form an anatomical bridge between the vasculature and neuronal
      synapses. Recent work suggests that they play a key role in regulating brain
      energy supply by increasing blood flow to regions where neurons are active, and
      setting the baseline level of blood flow. Controversy persists over whether
      lactate derived from astrocyte glycolysis is used to power oxidative
      phosphorylation in neurons, but astrocytes sustain neuronal ATP production by
      recycling neurotransmitter glutamate that would otherwise need to be
      resynthesised from glucose, and by providing a short-term energy store in the
      form of glycogen that can be mobilised when neurons are active.

PMID- 29054040
TI  - Myelin plasticity and behaviour-connecting the dots.
AB  - Myelin sheaths in the vertebrate nervous system enable faster impulse
      propagation, while myelinating glia provide vital support to axons. Once
      considered a static insulator, converging evidence now suggests that myelin in
      the central nervous system can be dynamically regulated by neuronal activity and
      continues to participate in nervous system plasticity beyond development. While
      the link between experience and myelination gains increased recognition, it is
      still unclear what role such adaptive myelination plays in facilitating and
      shaping behaviour. Additionally, fundamental mechanisms and principles underlying
      myelin remodelling remain poorly understood. In this review, we will discuss new
      insights into the link between myelin plasticity and behaviour, as well as
      mechanistic aspects of myelin remodelling that may help to elucidate this
      intriguing process.

PMID- 29054041
TI  - Cardiovascular, obstetric and neonatal outcomes in women with previous fontan
      repair.
AB  - OBJECTIVES: To determine cardiovascular, obstetric and neonatal outcomes of
      pregnancies in women who have a Fontan circulation. METHODS: A retrospective case
      note review of all women with a Fontan circulation who attended the joint
      obstetric cardiac antenatal clinic at St Mary's Hospital, Manchester (UK) between
      2004 and 2016 was performed. RESULTS: In total, there were 19 pregnancies in 9
      women with a history of Fontan repair. 23 women with univentricular physiology
      attended in this time period. 10 pregnancies (53%) resulted in live births; 1 in
      a stillbirth at 31 weeks gestation and 8 in miscarriage. Cardiovascular
      complications occurred in 2 pregnancies (11%). There were no thrombotic events,
      arrhythmias, myocardial infarction, or endocarditis in the antenatal or postnatal
      period. Obstetric complications included miscarriage (26% first trimester, 16%
      second trimester), along with premature delivery (24-36+6) (80%) and fetal growth
      restriction (70%). The majority of women were delivered by caesarean section
      (60%). CONCLUSIONS: Women who become pregnant following a Fontan repair carry an
      increased risk of cardiovascular complications. Fetal and neonatal complication
      rates are high and emphasize the importance of thorough, multidisciplinary, pre
      conceptual assessment and counseling to allow patients to make informed decisions
      regarding future pregnancy.

PMID- 29054042
TI  - Spontaneous hemoperitoneum in pregnancy (SHiP) and endometriosis - A systematic
      review of the recent literature.
AB  - Spontaneous Hemoperitoneum in Pregnancy (SHiP), an unprovoked (nontraumatic)
      intraperitoneal bleeding in pregnancy (up to 42days postpartum), is associated
      with serious adverse pregnancy outcomes. To evaluate the clinical consequences of
      SHiP and its association with endometriosis, a systematic review was conducted
      according to the PRISMA guidelines. PubMed, Embase.com and Thomson Reuters/Web of
      Science were searched for articles published since the latest review (August
      2008) until September 2016. After assessment for eligibility, forty-four articles
      were included in this systematic review, describing 59 cases of SHiP.
      Endometriosis was present in 33/59 cases (55.9%), most often diagnosed prior to
      pregnancy. An association between the severity of SHiP and the stage of
      endometriosis could not be found. In the majority of cases, SHiP occurred in the
      third trimester of pregnancy (30/59 cases (50.8%)); women presented with
      (sub)acute abdominal pain (56/59 cases (94.9%)), hypovolemic shock (28/59 cases
      (47.5%)) and/or a decreased level of hemoglobin (37/59 cases (62.7%)). Signs of
      fetal distress were observed in 24/59 cases (40.7%). Imaging confirmed free
      peritoneal fluid in (37/59 cases (62.7%)). At time of surgery active bleeding was
      revealed in 51/56 cases (91,1%), originating from endometriotic implants (11/51
      cases (21.6%)), ruptured utero-ovarian vessels (29/51 cases (56.8%)), hemorrhagic
      nodules of decidualized cells (1/51 cases (2.0%)) or a combination (10/51 cases
      (19.6%)). Median amount of hemoperitoneum was 1600mL (IQR 1000mL-2500mL). From
      the 45/59 cases (76.3%) in which surgical interventions was carried out during
      pregnancy, 7/45 cases (15.6%) reported a successful continuation of pregnancy.
      5/59 cases reported recurrence of SHiP (recurrence rate 8.5%). The perinatal
      mortality rate was 26.9% (18/67 fetus), one maternal death was reported (1/59
      cases (1,7%)). In conclusion, SHiP is a very serious complication of pregnancy,
      highly associated with adverse pregnancy outcomes and particularly relevant to
      women with endometriosis. Currently preventive measures are lacking, therefore
      increasing the awareness and recognition of SHiP is crucial to improve pregnancy
      outcomes.

PMID- 29054043
TI  - Systematic approaches for targeting an atom-probe tomography sample fabricated in
      a thin TEM specimen: Correlative structural, chemical and 3-D reconstruction
      analyses.
AB  - Atom-probe tomography (APT) is a unique analysis tool that enables true three
      dimensional (3-D) analyses with sub-nano scale spatial resolution. Recent
      implementations of the local-electrode atom-probe (LEAP) tomograph with
      ultraviolet laser pulsing have significantly expanded the research applications
      of APT. The small field-of-view of a needle-shaped specimen with a less than 100
      nm diam. is, however, a major limitation for analyzing materials. The systematic
      approaches for site-specific targeting of an APT nanotip in a transmission
      electron microscope (TEM) of a thin sample are introduced to solve the
      geometrical limitations of a sharpened APT nanotip. In addition to "coupling APT
      to TEM", the technique presented here allows for targeting the preparation of an
      APT tip based on TEM observation of a much larger area than what is captured in
      the APT tip. The correlative methods have synergies for not only high-resolution
      structural analyses but also for obtaining chemical information. Chemical
      analyses in a TEM, both energy-dispersive X-ray spectroscopy (EDS) and electron
      energy-loss spectroscopy (EELS), are performed and compared with the APT chemical
      analyses of a carbide phase (M7C3) precipitate at a grain boundary in a Ni-based
      alloy. Additionally, a TEM image of a sharpened APT nanotip is utilized for
      calculation of the detection area ratio of an APT nanotip by comparison with a
      TEM image for precise tomographic reconstructions. A grain-boundary/carbide
      precipitate triple junction is used to attain precise positioning of an APT
      nanotip in an analyzed TEM specimen.

PMID- 29054044
TI  - Metacognitive deficits in categorization tasks in a population with impaired
      inner speech.
AB  - This study examines the relation of language use to a person's ability to perform
      categorization tasks and to assess their own abilities in those categorization
      tasks. A silent rhyming task was used to confirm that a group of people with post
      stroke aphasia (PWA) had corresponding covert language production (or "inner
      speech") impairments. The performance of the PWA was then compared to that of age
      and education-matched healthy controls on three kinds of categorization tasks
      and on metacognitive self-assessments of their performance on those tasks. The
      PWA showed no deficits in their ability to categorize objects for any of the
      three trial types (visual, thematic, and categorial). However, on the categorial
      trials, their metacognitive assessments of whether they had categorized correctly
      were less reliable than those of the control group. The categorial trials were
      distinguished from the others by the fact that the categorization could not be
      based on some immediately perceptible feature or on the objects' being found
      together in a type of scenario or setting. This result offers preliminary
      evidence for a link between covert language use and a specific form of
      metacognition.

PMID- 29054045
TI  - Analysis of data collected from right and left limbs: Accounting for dependence
      and improving statistical efficiency in musculoskeletal research.
AB  - OBJECTIVES: Statistical techniques currently used in musculoskeletal research
      often inefficiently account for paired-limb measurements or the relationship
      between measurements taken from multiple regions within limbs. This study
      compared three commonly used analysis methods with a mixed-models approach that
      appropriately accounted for the association between limbs, regions, and trials
      and that utilised all information available from repeated trials. METHOD: Four
      analysis were applied to an existing data set containing plantar pressure data,
      which was collected for seven masked regions on right and left feet, over three
      trials, across three participant groups. Methods 1-3 averaged data over trials
      and analysed right foot data (Method 1), data from a randomly selected foot
      (Method 2), and averaged right and left foot data (Method 3). Method 4 used all
      available data in a mixed-effects regression that accounted for repeated measures
      taken for each foot, foot region and trial. Confidence interval widths for the
      mean differences between groups for each foot region were used as a criterion for
      comparison of statistical efficiency. RESULTS: Mean differences in pressure
      between groups were similar across methods for each foot region, while the
      confidence interval widths were consistently smaller for Method 4. Method 4 also
      revealed significant between-group differences that were not detected by Methods
      1-3. CONCLUSION: A mixed effects linear model approach generates improved
      efficiency and power by producing more precise estimates compared to alternative
      approaches that discard information in the process of accounting for paired-limb
      measurements. This approach is recommended in generating more clinically sound
      and statistically efficient research outputs.

PMID- 29054046
TI  - Surface modification of polyisobutylene via grafting amino acid-based poly
      (acryloyl-6-aminocaproic acid) as multifunctional material.
AB  - Amino acid-based P(acryloyl-6-aminocaproic acid) (PAACA) brushes were fabricated
      on polyisobutylene (PIB) surface combined with plasma pre-treatment and UV
      induced grafting polymerization to construct an antifouling and functional
      material. The hydrophilicity and hemocompatibility of PIB were largely improved
      by surface modification of AACA, which were confirmed by water contact angle and
      platelet adhesion, respectively. PAACA brushes were precisely located onto the
      surface of PIB to create a patterned PIB-g-PAACA structure, and then the carboxyl
      groups on PAACA was activated to immobilize functional protein-Concanavalin A
      (Con A). The obtained Con A-coupled microdomains could further capture
      erythrocytes. This method developed a platform on commercial PIB surface via
      amino acid-based polymer brushes which had a promising application in drug
      delivery and disease diagnosis.

PMID- 29054047
TI  - Application of transglycosylated stevia and hesperidin as drug carriers to
      enhance biopharmaceutical properties of poorly-soluble artemisinin.
AB  - Biopharmaceutical properties of poorly water-soluble antimalarial drug,
      Artemisinin (ART), were improved by formulating amorphous solid dispersions with
      transglycosylated food additives (Hsp-G and Stevia-G) via co-spray drying. Both
      the formulated ART/Hsp-G and ART/Stevia-G showed superior dissolution properties
      with a burst release of more than 95% of drug within 5 min, whereas untreated ART
      dissolved only 4% in 5min. The supersaturation solubility of the formulated ART
      was enhanced by 2-fold as compared with untreated counterpart. The storage
      stability tests indicated that these formulations chemically stable at room
      temperature and under low humidity (<18% RH) conditions. However, high humidity
      (75% RH) induced re-crystallization and caused changes in the physical appearance
      of the solid dispersions. In addition, both the food additives and ART formulated
      samples showed low cytotoxicity to Caco-2 cell line suggesting their good
      biocompatibility. Thus, the formation of solid dispersions of ART with
      transglycosylated food additives is a potentially safe and effective approach to
      enhance the bioavailability of poorly water-soluble ART.

PMID- 29054048
TI  - Synthesis and characterization of incorporating mussel mimetic moieties into
      photoactive hydrogel adhesive.
AB  - Surgical adhesive is the optimal candidate for the replacement of traditional
      mechanical wound closure. In our paper, mussel adhesive proteins inspired
      hydrogel adhesive was prepared with 3, 4-dihydroxyphyenylanine acrylamide (DOPA
      AA), poly (ethylene glycol) diacrylate (PEGDAA) and thiolated chitosan (CSS) by
      UV irradiation. DOPA-AA, containing catechol group and vinyl group, was
      successful synthesized and characterized by FTIR and 1HNMR. The gelation time,
      equilibrium water content, degradation, materials properties and adhesive
      strength of the hydrogels were studied. We found that the gelation time was
      retarded and the materials mechanical strength was decreased because of the
      inhibitory effect of catechol group. Equilibrium water content was slightly
      affect by the increasing concentration of DOPA-AA (1-5%). Nevertheless, catechol
      group can remarkably improve the adhesive properties because of the complex and
      durable interactions of the hydrogel, especially, the interaction between the
      thiol group of CSS and catechol group of DOPA-AA, which also greatly slowed down
      the degradation of the adhesive hydrogels. CSS and DOPA-AA was introduced to
      ensure the adhesive properties, DOPA-AA lend the adhesive nature to hydrogel and
      CSS can protect the catechol group from oxidation and enhance durable adhesion.
      Moreover, cytotoxicity of the resulting hydrogels showed that the L929 cell
      viability was weaken, it mostly probably induced by the catechol oxidation.

PMID- 29054049
TI  - Individual variability in clinical effect and tolerability of opioid analgesics -
      Importance of drug interactions and pharmacogenetics.
AB  - BACKGROUND: As pain is often a comorbid condition, many patients use opioid
      analgesics in combination with several other drugs. This implies a generally
      increased risk of drug interactions, which along with inherent pharmacogenetic
      variability and other factors may cause differences in therapeutic response of
      opioids. AIM: To provide an overview of interactions and pharmacogenetic
      variability of relevance for individual differences in effect and tolerability of
      opioid analgesics, which physicians and other healthcare professionals should be
      aware of in clinical practice. METHODS: The article was based on unsystematic
      searches in PubMed to identify literature highlighting the clinical impact of
      drug interactions and pharmacogenetics as sources of variable response of opioid
      analgesics. RESULTS: Cytochrome P450 (CYP)-mediated metabolism is an important
      process for both clinically relevant interactions and pharmacogenetic variability
      of several opioids. Concomitant use of CYP inhibitors (e.g. paroxetine,
      fluoxetine and bupropion) or inducers (e.g. carbamazepine, phenobarbital and
      phenytoin) could counteract the clinical effect or trigger side effects of
      analgesics in the same manner as genetically determined differences in CYP2D6
      mediated metabolism of many opioids. Moreover, combination treatment with drugs
      that inhibit or induce P-glycoprotein (ABCB1), a blood-brain barrier efflux
      transporter, may alter the amount ('dose') of opioids distributed to the brain.
      At the pharmacodynamic level, it is crucial to be aware of the potential risk of
      interaction causing serotonergic syndrome when combining opioids and serotonergic
      drugs, in particular antidepressants inhibiting serotonin reuptake (SSRIs and
      SNRIs). Regarding pharmacogenetics at the receptor level of pain treatment, the
      knowledge is currently scarce, but an allelic variant of the MU1 opioid receptor
      (OPRM1) gene has been associated with higher dosage requirement to achieve
      analgesia. CONCLUSIONS AND IMPLICATIONS: Drug interactions and pharmacogenetic
      differences may lead to therapeutic failure or serious side effects of opioid
      analgesics. Many interactions involve combinations with antidepressants and
      antiepileptics, which are highly relevant drugs in patients suffering from pain.
      To prevent unfavourable drug interactions it is important that clinicians pay
      close attention and use electronic drug interaction checkers when treatments are
      initiated or discontinued. For the management of issues related to
      pharmacogenetic differences, blood-based CYP genotyping is available as routine
      test at many laboratories, and provide a valuable tool for proper choice of drugs
      and doses for treatment of pain and other diseases.

PMID- 29054050
TI  - Thermal neutron radiative capture on cadmium as a counting technique at the INES
      beam line at ISIS: A preliminary investigation of detector cross-talk.
AB  - Experimental tests are presented that assess the cross-talk level among three
      scintillation detectors used as neutron counters exploiting the thermal neutron
      radiative capture on Cd. The measurements were done at the INES diffractometer
      operating at the ISIS spallation neutron source (Rutherford Appleton Laboratory,
      UK). These tests follow a preliminary set of measurements performed on the same
      instrument to study the effectiveness of this thermal neutron counting strategy
      in neutron diffraction measurements, typically performed on INES using squashed
      3He filled gas tubes. The experimental data were collected in two different
      geometrical configurations of the detectors and compared to results of Monte
      Carlo simulations, performed using the MCNP code.

PMID- 29054051
TI  - The incidence and risk factors of epilepsy in children born preterm: A nationwide
      register study.
AB  - OBJECTIVES: The aim was to compare the incidence of epilepsy between very preterm
      (VP) (<32+0 weeks), moderately preterm (MP) (32+0-33+6 weeks), late preterm (LP)
      (34+0-36+6 weeks) and term infants (>=37 weeks) and to establish and compare risk
      factors of epilepsy in these groups. METHODS: The national register study
      included all live born infants in Finland in 1991-2008. Excluding infants with
      missing gestational age, a total of 1,033,349 infants were included in the
      analysis and they were analyzed in four subgroups (VP, MP, LP and term) and three
      time periods (1991-1995, 1996-2001 and 2002-2008). RESULTS: 5611 (0.54%) children
      with epilepsy were diagnosed. The incidence of epilepsy was 2.53% in the VP,
      1.08% in the MP, 0.75% in the LP and 0.51% in the term group. Intracranial
      hemorrhage (OR 3.48; 95% CI 2.47-4.89) and convulsions in the neonatal period (OR
      13.4; 95% CI 10.2-17.6) were associated with an increased risk of epilepsy.
      Compared to the term group, preterm birth (VP OR 4.59; 95% CI 3.79-5.57, MP 1.97;
      1.48-2.63, LP 1.44; 1.25-1.68) was associated with an increased risk of epilepsy
      after adjusting for maternal, pregnancy, delivery and sex variables. CONCLUSIONS:
      The incidence of epilepsy decreased by advancing gestational age at birth and
      preterm birth predicted an increased risk of epilepsy in childhood. Intracranial
      hemorrhage and neonatal convulsions were strongly associated with an increased
      risk of epilepsy.

PMID- 29054052
TI  - Synthesis and binding affinity analysis of alpha1-2- and alpha1-6-O/S-linked
      dimannosides for the elucidation of sulfur in glycosidic bonds using quartz
      crystal microbalance sensors.
AB  - The role of sulfur in glycosidic bonds has been evaluated using quartz crystal
      microbalance methodology. Synthetic routes towards alpha1-2- and alpha1-6-linked
      dimannosides with S- or O-glycosidic bonds have been developed, and the
      recognition properties assessed in competition binding assays with the cognate
      lectin concanavalin A. Mannose-presenting QCM sensors were produced using
      photoinitiated, nitrene-mediated immobilization methods, and the subsequent
      binding study was performed in an automated flow-through instrumentation, and
      correlated with data from isothermal titration calorimetry. The recorded Kd
      values corresponded well with reported binding affinities for the O-linked
      dimannosides with affinities for the alpha1-2-linked dimannosides in the lower
      micromolar range. The S-linked analogs showed slightly disparate effects, where
      the alpha1-6-linked analog showed weaker affinity than the O-linked dimannoside,
      as well as positive apparent cooperativity, whereas the alpha1-2-analog displayed
      very similar binding compared to the O-linked structure.

PMID- 29054053
TI  - Leptin reduces microRNA-122 level in hepatic stellate cells in vitro and in vivo.
AB  - Obese patients, often accompanied by hyperleptinemia, are more likely to develop
      liver fibrosis. Leptin, an adipocyte-derived hormone, augments inflammatory in
      liver and promotes hepatic stellate cell (HSC) activation (a key step for liver
      fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant
      liver-specific miRNA and can attenuate liver fibrosis. This study examined the
      effect of leptin on miR-122 level in HSCs in vivo and in vitro. Results
      demonstrated that leptin reduced the levels of both miR-122 (mature miR-122) and
      primary miR-122 (pri-miR-122). The effects of leptin on the levels of miR-122 and
      pri-miR-122 were through at least hedgehog pathway. Leptin-induced decrease in
      sterol regulatory element-binding protein-1c (SREBP-1c) has been shown to
      contribute to leptin-induced HSC activation. We revealed a mutual promotional
      effect between SREBP-1c and miR-122. Further experiments indicated that miR-122
      inhibited leptin-induced liver fibrosis in leptin-deficient mouse model. These
      data have potential implications for clarifying the mechanisms of hepatic
      fibrogenesis associated with elevated leptin level in human such as obese
      patients.

PMID- 29054054
TI  - Conformational analysis of the human chemokine receptor CXCR3.
AB  - In the last years, some studies showed the patho-genetic role of CXCR3 bound to
      its ligands in many human inflammatory diseases and cancers. Thus, the blockage
      of the CXCR3 interaction site to its ligands is seen as a possible therapeutic
      target for the treatment of cancer. The presence of flexible regions in the
      chemokine receptors determines their capability to develop specific mechanisms of
      action. We have recently focused on the features of the N-terminal region of
      human CXCR3 free in solution, where we demonstrate the presence of numerous
      conformational ensembles, dynamically stabilized by H-bonds. Since up to now no
      structure was experimentally determined for CXCR3, we decided to approach the
      study of its conformational behavior by molecular dynamics simulations, in a
      lipid bilayer, surrounded of water, at neutral pH and 300K. Furthermore, we
      modeled the CXCR3/CXCL11 complex, where CXCL11 is one of its natural ligands. The
      aim of this work is to have a vision as realistic as possible in dynamic terms of
      the biological mechanism that drives the search for the ligand, its interaction
      and the formation of a stable complex between CXCR3 and CXCL11. Overall, our
      approach has been able to describe the structural events which dynamically
      characterize the molecular mechanisms involved in the binding of CXCR3 to CXCL11
      and the critical role exerted by its N-terminal region in "hunting" and capturing
      the ligand.

PMID- 29054055
TI  - An integrated green process: Subcritical water, enzymatic hydrolysis, and
      fermentation, for biohydrogen production from coconut husk.
AB  - The objective of this work is to develop an integrated green process of
      subcritical water (SCW), enzymatic hydrolysis and fermentation of coconut husk
      (CCH) to biohydrogen. The maximum sugar yield was obtained at mild severity
      factor. This was confirmed by the degradation of hemicellulose, cellulose and
      lignin. The tendency of the changing of sugar yield as a result of increasing
      severity factor was opposite to the tendency of pH change. It was found that CO2
      gave a different tendency of severity factor compared to N2 as the pressurizing
      gas. The result of SEM analysis confirmed the structural changes during SCW
      pretreatment. This study integrated three steps all of which are green processes
      which ensured an environmentally friendly process to produce a clean biohydrogen.

PMID- 29054056
TI  - Supercritical water gasification of sewage sludge in continuous reactor.
AB  - In this study, a process for the continuous recovery of phosphorus and generation
      of gas from sewage sludge is investigated for the first time using supercritical
      water gasification (SCWG). A continuous reactor was employed and experiments were
      conducted by varying the temperature (500-600  degrees C) and residence time (5
      60 s) while fixing the pressure at 25 MPa. The behavior of phosphorus during the
      SCWG process was studied. The effect of the temperature and time on the
      composition of the product gas was also investigated. A model of the reaction
      kinetics for the SCWG of sewage sludge was developed. The organic phosphorus (OP)
      was rapidly converted into inorganic phosphorus (IP) within a short residence
      time of 10 s. The gaseous products were mainly composed of H2, CO2, and CH4. The
      reaction followed first order kinetics, and the model was found to fit the
      experimental data well.

PMID- 29054057
TI  - Removing ethinylestradiol from wastewater by microalgae mutant Chlorella PY-ZU1
      with CO2 fixation.
AB  - Removal of endocrine-disrupting chemical ethinylestradiol (EE2) from wastewater
      by microalgal mutant Chlorella PY-ZU1 under 15% CO2 were investigated. Moreover,
      the effects of EE2 on microscopic structure and antioxidation ability of
      microalgal cells were determined. EE2 concentrations in range of 0.01-5 mg L-1
      stimulated microalgal growth. Increasing the original EE2 concentration from 0 to
      5 mg L-1 increased the cell fractal dimension from 1.38 to 1.59 and reduced the
      cell size from 5.18 to 3.41 MUm. Meanwhile, superoxide dismutase and catalase
      activities, which represented cellular antioxidant capacity, first increased from
      44.59 and 0.54 U mL-1 to peak values of 65.57 and 1.49 U mL-1, respectively, and
      then correspondingly decreased to 34.36 and 0.36 U mL-1. Malondialdehyde content
      that indicated the cell oxidation damage degree first decreased from 2.57 to 2.03
      nmol mL-1, then increased to 2.59 nmol mL-1. The highest EE2 removal efficiency
      of 94% by Chlorella PY-ZU1 was achieved at the original EE2 concentration of 5 mg
      L-1.

PMID- 29054058
TI  - Study on improving anaerobic co-digestion of cow manure and corn straw by fruit
      and vegetable waste: Methane production and microbial community in CSTR process.
AB  - Based on continuous anaerobic co-digestion of cow manure with available carbon
      slowly released corn straw, the effect of adding available carbon quickly
      released fruit and vegetable waste (FVW) was explored, meanwhile microbial
      community variation was studied in this study. When the FVW added was 5% and 1%,
      the methane production of the cow manure and corn straw was improved, and the
      start-up process was shortened. With higher proportion of FVW to 5%, the
      performance was superior with a mean methane yield increase of 22.4%, and a
      greater variation of bacterial communities was observed. FVW enhanced the
      variation of the bacterial communities. The microbial community structure changed
      during fermentation and showed a trend toward a diverse and balance system.
      Therefore, the available carbon quickly released FVW was helpful to improve the
      anaerobic co-digestion of the cow manure and available carbon slowly released
      corn straw.

PMID- 29054059
TI  - Enhancement of sludge reduction by ultrasonic pretreatment and packing carriers
      in the anaerobic side-stream reactor: Performance, sludge characteristics and
      microbial community structure.
AB  - Effects of ultrasonic pretreatment and packing carriers on sludge reduction,
      settleability, dewaterability and microbial community structure in the anaerobic
      side-stream reactor (ASSR) were investigated with three anaerobic reactors
      operated in parallel. Ultrasonication from 3.65% in the ASSR to 5.08%, and
      packing carriers further enhanced the efficiency to 19.2%. Ultrasonic
      pretreatment of sludge decreased oxidation-reduction potential in ASSR and
      enhanced the release of intracellular substances. The deterioration of sludge
      settleability and dewaterability in the ASSR after ultrasonic pretreatment was
      improved by packing carriers. Illumina-MiSeq sequencing showed that microbial
      richness and diversity increased after ultrasonic pretreatment and packing
      carriers in the ASSR. Packing carriers favored the growth of slow grower
      (Dechloromonas), fermentative bacteria (Draconibacteriaceae, Fusibacter,
      Acidaminobacter) and floc-forming bacteria (Zoogloea), while hydrolytic and
      predatory bacteria (Saprospiraceae_unculture) and slow grower (Thauera) was
      enriched in the ASSR.

PMID- 29054060
TI  - Effect of solid state fermentation of peanut shell on its dye adsorption
      performance.
AB  - The effect of solid state fermentation of peanut shell to produce beneficial
      laccase and on its dye adsorption performance was evaluated. The resulting
      residues from solid fermentation were tested as sorbents (designated as SFs) in
      comparison to the raw peanut shell (RPS) for their ability to remove crystal
      violet from water. The fermentation process reduced the adsorption capacity (qm)
      of SF by about 50%, and changed the sorptive behavior when compared to the RPS.
      The Langmuir model was more suitable for fitting adsorption by SFs. qm was
      positively correlated with the surface area of peanut shell, but negatively
      correlated with acid detergent lignin content. For all the sorbents tested, the
      process was spontaneous and endothermic, and the adsorption followed both the
      pseudo 1st and 2nd order kinetic model and the film diffusion model. Dye
      adsorption efficiency was greater when SFs dispersed solution than when placed in
      filter packets.

PMID- 29054061
TI  - Microbial characteristics analysis and kinetic studies on substrate composition
      to methane after microbial and nutritional regulation of fruit and vegetable
      wastes anaerobic digestion.
AB  - This study firstly evaluated the microbial role when choosing the acclimated
      anaerobic granular sludge (AGS) and waste activated sludge (WAS) as microbial and
      nutritional regulators to improve the biomethanation of fruit and vegetable
      wastes (FVW). Results showed that the enriched hydrogenotrophic methanogens, and
      Firmicutes and Spirochaeta in the AGS were responsible for the enhanced methane
      yield. A synthetic waste representing the mixture of WAS and FVW was then used to
      investigate the influences of different substrate composition on methane
      generations. The optimal mass ratio of carbohydrate/protein/cellulose was
      observed to be 50:45:5, and the corresponding methane yield was 411mL/g-VSadded.
      Methane kinetic studies suggested that the modified Gompertz model fitted better
      with those substrates of carbohydrate- than protein-predominated. Parameter
      results indicated that the maximum methane yield and production rate were
      enhanced firstly and then reduced with the decreasing carbohydrate and increasing
      protein percentages; the lag phase time however increased continuously.

PMID- 29054062
TI  - The chemostat metabolite spectra of alkaline mixed culture fermentation under
      mesophilic, thermophilic, and extreme-thermophilic conditions.
AB  - Alkaline mixed culture fermentation (MCF) is a promising technology for reducing
      organic waste and producing biochemicals. However, chemostat metabolite spectra
      that are necessary for constructing a model and analyzing factors are seldom
      reported. In the present study, the effects of pH on the metabolites distribution
      in mesophilic (35  degrees C), thermophilic (55  degrees C), and extreme
      thermophilic (70  degrees C) alkaline MCF were demonstrated. A chemical oxygen
      demand balance above 80% was achieved, and the main metabolites included acetate,
      ethanol, propionate, lactate, and formate. The yields of ethanol and formate
      increased as pH was increased from 7.5 to higher pH under mesophilic and
      thermophilic conditions, while the yields of acetate, lactate, and/or propionate
      decreased. The yields of ethanol, acetate, and formate increased under extreme
      thermophilic conditions as pH was increased from 7.5 to 9.0, whereas lactate and
      hydrogen yields decreased. Low biomass yield under thermophilic and extreme
      thermophilic conditions benefited higher metabolite production and minimized the
      accumulation of sludge.

PMID- 29054063
TI  - Valorisation of Tectona Grandis tree sawdust through the production of high
      activated carbon for environment applications.
AB  - This work presents a first approach concerning the use of Tectona Grandis tree
      sawdust (from East Timor) for high activated carbon production, by physical
      activation with carbon dioxide at different temperatures. The activated carbons
      (AC) obtained exhibit a well-developed porous structure with a pore size
      distribution varying from micro to mesopores. Selected AC was successfully
      evaluated for pesticide removal, specific to 4-chloro-2-methylphenoxyacetic acid,
      from the liquid phase. The results presented are very promising, allowing to
      establish that Tectona Grandis sawdust is as an excellent precursor for the basic
      AC production and allow to expect good performance of theses adsorbents on the
      removal of a broad range of pollutants. It should also be noted that, this
      achievement is very relevant for developing countries, such East Timor, where
      Tectona Grandis sawdust is available and may constitute a source of income
      creating a handle to the technical and industrial development of this region.

PMID- 29054064
TI  - Continuous hydrogen and methane production from Agave tequilana bagasse
      hydrolysate by sequential process to maximize energy recovery efficiency.
AB  - Continuous H2 and CH4 production in a two-stage process to increase energy
      recovery from agave bagasse enzymatic-hydrolysate was studied. In the first
      stage, the effect of organic loading rate (OLR) and stirring speed on volumetric
      hydrogen production rate (VHPR) was evaluated in a continuous stirred tank
      reactor (CSTR); by controlling the homoacetogenesis with the agitation speed and
      maintaining an OLR of 44 g COD/L-d, it was possible to reach a VHPR of 6 L H2/L
      d, equivalent to 1.34 kJ/g bagasse. In the second stage, the effluent from CSTR
      was used as substrate to feed a UASB reactor for CH4 production. Volumetric
      methane production rate (VMPR) of 6.4 L CH4/L-d was achieved with a high OLR (20
      g COD/L-d) and short hydraulic retention time (HRT, 14 h), producing 225 mL CH4/g
      bagasse equivalent to 7.88 kJ/g bagasse. The two-stage continuous process
      significantly increased energy conversion efficiency (56%) compared to one-stage
      hydrogen production (8.2%).

PMID- 29054065
TI  - Investigating desorption during ethanol elution to improve the quality and
      antioxidant activity of xylo-oligosaccharides from corn stalk.
AB  - As the most representative of lignocellulosic materials, corn stalk (CS) will be
      a great candidate to produce xylo-oligosaccharides (XOS). Owing to the high
      impurity content of the XOS produced by directly enzymatic hydrolysis of xylan
      extracted from CS, subsequent refining steps are essential. The present study was
      aimed to investigate desorption during ethanol elution to improve the quality and
      antioxidant activity of XOS from CS. The desorption was systematically
      investigated after optimizing the elution conditions. The results showed that it
      had an elution watershed when the volume ratio was 2:1. More interestingly, XOS
      had a obvious priorities of desorption during ethanol gradient elution. The
      highest purity of XOS was 98.12% from 30% ethanol eluate. Antioxidant activity
      assay showed that the highest radical scavenging activity of XOS was 89.89%
      obtained from 70% ethanol eluate at a concentration of 3 mg/mL, which could be
      used in antioxidant food, feed additives.

PMID- 29054066
TI  - Torrefaction of corncob to produce charcoal under nitrogen and carbon dioxide
      atmospheres.
AB  - Corncob was torrefied under nitrogen and carbon dioxide atmospheres at 220-300 
      degrees C, obtaining solid products with mass yields of 69.38-95.03% and 67.20
      94.99% and higher heating values of 16.58-24.77 MJ/kg and 16.68-24.10 MJ/kg,
      respectively. The changes of physicochemical properties of the charcoal was
      evaluated by many spectroscopies, contact angle determination, and combustion
      test. Hemicelluloses were not detected for the torrefaction under the hard
      conditions. As the severity increased, C concentration raised while H and O
      concentrations reduced. Combustion test showed that the burnout temperature of
      charcoal declined with the elevation of reaction temperature, and torrefaction at
      a high temperature shortened the time for the whole combustion process. Base on
      the data, torrefaction at 260  degrees C under carbon dioxide was recommended for
      the torrefaction of corncob.

PMID- 29054067
TI  - A novel surface plasmon resonance biosensor based on the PDA-AgNPs-PDA-Au film
      sensing platform for horse IgG detection.
AB  - Herein we report a novel polydopamine-silver nanoparticle-polydopamine-gold (PDA
      AgNPs-PDA-Au) film based surface plasmon resonance (SPR) biosensor for horse IgG
      detection. The PDA-AgNPs-PDA-Au film sensing platform was built on Au-film via
      layer-by-layer self-assembly. Ag ion was reduced in situ to AgNPs in presence of
      PDA. The top PDA layer can prevent AgNPs from being oxidized and connect with
      antibody via Schiff alkali reaction directly. The morphology and thickness of the
      modified gold film were characterized using scanning electron microscope and
      Talystep. Experimental results show that the PDA-AgNPs-PDA-Au film sensing
      platform is stable, regenerative and sensitive for horse IgG detection. The
      detection limit of horse IgG obtained with the present biosensor is 0.625MUgmL-1,
      which is 2-fold and 4-fold lower than that obtained with biosensor based on PDA
      modified Au film and conventional biosensor based on MPA, respectively.
      Furthermore, when challenged to real serum samples, our sensor exhibited
      excellent specificity to horse IgG, suggesting its potential for industrial
      application.

PMID- 29054068
TI  - Quantitative determination of additive Chlorantraniliprole in Abamectin
      preparation: Investigation of bootstrapping soft shrinkage approach by mid
      infrared spectroscopy.
AB  - A novel method, mid-infrared (MIR) spectroscopy, which enables the determination
      of Chlorantraniliprole in Abamectin within minutes, is proposed. We further
      evaluate the prediction ability of four wavelength selection methods, including
      bootstrapping soft shrinkage approach (BOSS), Monte Carlo uninformative variable
      elimination (MCUVE), genetic algorithm partial least squares (GA-PLS) and
      competitive adaptive reweighted sampling (CARS) respectively. The results showed
      that BOSS method obtained the lowest root mean squared error of cross validation
      (RMSECV) (0.0245) and root mean squared error of prediction (RMSEP) (0.0271), as
      well as the highest coefficient of determination of cross-validation (Qcv2)
      (0.9998) and the coefficient of determination of test set (Q2test) (0.9989),
      which demonstrated that the mid infrared spectroscopy can be used to detect
      Chlorantraniliprole in Abamectin conveniently. Meanwhile, a suitable wavelength
      selection method (BOSS) is essential to conducting a component spectral analysis.

PMID- 29054069
TI  - Postmortem distribution of chlorpyrifos-methyl, fenitrothion, and their
      metabolites in body fluids and organ tissues of an intoxication case.
AB  - We herein report a fatal intoxication case caused by the ingestion of the
      insecticides chlorpyrifos-methyl (CPFM) and fenitrothion (MEP). A 70-year-old man
      was found dead in his house and a cup containing a small amount of agricultural
      chemicals was on the table near his body. External and internal examinations
      revealed no injuries. In a gas chromatography-mass spectrometry (GC-MS) screening
      test, CPFM, MEP, and their metabolites, 3,5,6-trichloro-2-pyridinol (TCPY) and 3
      methyl-4-nitrophenol (3MNP), respectively, were qualitatively detected in his
      stomach contents. The concentrations (ug/g) of CPFM, TCPY, MEP, and 3MNP in the
      extracts of each body fluid and organ tissue were assessed by GC-MS and were as
      follows: 27.8, 56.2, 17.2, and 2.82 (heart blood); 6.60, 42.9, 1.80, and 2.59
      (peripheral blood); 0.0821, 45.9, 2,09, and 102 (urine); 21.4, 26.6, 76.2, and
      3.83 (brain (frontal portion)); 16.1, 101, 9.67, and 1.26 (liver); 7.45, 101,
      21.4, and 26.1 (right kidney); and 73,500, 9750, 232,000, and 1880 (stomach
      contents), respectively. Based on these results and autopsy findings, the cause
      of death was acute fatal intoxication by CPFM and MEP.

PMID- 29054070
TI  - Bedside implantation of a new temporary vena cava inferior filter - Safety and
      efficacy results of the European ANGEL-Registry.
AB  - PURPOSE: Pulmonary embolism (PE) is a frequently occurring complication in
      critically ill patients. Simultaneous occurrence of PE and life-threatening
      bleeding, may render medical anticoagulation impossible. For these patients,
      inferior vena cava filters (IVCF) present a valuable therapeutic alternative. The
      Angel(r) catheter is a novel IVCF that provides temporary protection from PE and
      is implanted at bedside. The primary objective of the European Angel(r) catheter
      registry is to evaluate the safety and efficacy of this IVCF. MATERIAL AND
      METHODS: The European Angel(r) catheter registry is an observational, multi
      centre registry. Patients from four countries and eight sites that have undergone
      Angel(r) catheter implantation between March 2013 and February 2017 were
      enrolled. RESULTS: A total of 114 critically ill patients were included. The main
      indication for implantation was a high-risk for PE in combination with
      contraindications for anticoagulation (69.3%). One clinically non-significant PE
      (0.9%) occurred in a patient with an indwelling Angel(r) catheter. No cases of
      catheter associated serious complications were observed. CONCLUSION: Data shows
      that the Angel(r) catheter is a safe and effective approach to overcome the acute
      phase of critically ill patients with a high risk for the development of PE or an
      established PE, when an anticoagulation therapy is contraindicated.

PMID- 29054071
TI  - Inactivation of bovine plasma amine oxidase by 1,1,1-trihalo-3-aminopropanes.
AB  - In this paper, we report the inactivation of copper containing bovine plasma
      amine oxidase (BPAO) by a series of saturated alkylamines containing halogen
      atoms at gamma-position, which are 1,1,1-trihalo-3-aminopropane, 1,1,1-trifluoro
      2-hydroxy-3-aminopropane, 1,1,1-trichloro-2-hydroxy-3-aminopropane, and 1,1,1
      trichloro-2-(2-phenethyloxy)-3-aminopropane. The trihalo-2-hydroxypropylamine
      analogs exhibited a time-dependent inactivation behavior of BPAO, with 1,1,1
      trifluoro-2-hydroxy-3-aminopropane as the most efficient inactivator. The
      incorporation of a OH group at beta-position increased inactivation efficiency by
      10-fold within the trifluoro analogs, and the incorporation of a phenethyloxy
      group at beta-position exhibited a higher efficiency by 3-fold within the
      trichloro analogs based on I75 values. All four compounds were found to be
      irreversible inactivators for BPAO.

PMID- 29054072
TI  - Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based
      redox signaling?
AB  - The reversible oxidation of protein cysteine residues (Cys-SH) is a key reaction
      in cellular redox signaling involving initial formation of sulfenic acids (Cys
      SOH), which are commonly detected using selective dimedone-based probes. Here, we
      report that significant portions of dimedone-tagged proteins are susceptible to
      cleavage by DTT reflecting the presence of perthiosulfenic acid species (Cys
      SSOH) due to similar oxidation of hydropersulfides (Cys-SSH), since Cys-S
      dimedone adducts are stable toward DTT. Combined studies using molecular
      modeling, mass spectrometry, and cell-based experiments indicate that Cys-SSH are
      readily oxidized to Cys-SSOH, which forms stable adducts with dimedone-based
      probes. We additionally confirm the presence of Cys-SSH within protein tyrosine
      kinases such as EGFR, and their apparent oxidation to Cys-SSOH in response NADPH
      oxidase activation, suggesting that such Cys-SSH oxidation may represent a novel,
      as yet uncharacterized, event in redox-based signaling.

PMID- 29054073
TI  - Discourse production of mandarin-speaking children with high-functioning autism:
      The effect of mental and action verbs' semantic-pragmatic features.
AB  - The present study investigated the syntactic and pragmatic performance of
      children with high-functioning autism (HFA) during a discourse production task
      with mental verbs. Children with HFA and typically developing (TD) children were
      matched by chronological age, verbal IQ (VIQ) and full-scale IQ (FIQ). We found
      that children with HFA tended to select a nominal object given a mental verb with
      either a nominal or clausal object. They committed few syntactic errors but
      generated syntactic stereotypes with mental verbs. However, this behavior was not
      observed with action verbs. Thus, children with HFA were specifically impaired in
      the argument structures of mental verbs. In pragmatic performance, children with
      HFA produced significantly fewer clauses or sentences with lower syntactic
      complexity for mental verbs than TD controls. This result might be due to the
      semantic-pragmatic impairment of children with HFA in the use of mental verbs.
      This study concludes that children with HFA were able to acquire the syntactic
      frames of mental verbs but were nevertheless impaired in the acquisition of
      pragmatic information inherent in those verbs.

PMID- 29054074
TI  - Temperature dependence of bioelectrochemical CO2 conversion and methane
      production with a mixed-culture biocathode.
AB  - This study evaluated the effect of temperature on methane production by CO2
      reduction during microbial electrosynthesis (MES) with a mixed-culture
      biocathode. Reactor performance, in terms of the amount and rate of methane
      production, current density, and coulombic efficiency, was compared at different
      temperatures. The microbial properties of the biocathode at each temperature were
      also analyzed by 16S rRNA gene sequencing. The results showed that the optimum
      temperature for methane production from CO2 reduction in MES with a mixed-culture
      cathode was 50 degrees C, with the highest amount and rate of methane production
      of 2.06+/-0.13mmol and 0.094+/-0.01mmolh-1, respectively. In the mixed-culture
      biocathode MES, the coulombic efficiency of methane formation was within a range
      of 19.15+/-2.31% to 73.94+/-2.18% due to by-product formation at the cathode,
      including volatile fatty acids and hydrogen. Microbial analysis demonstrated that
      temperature had an impact on the diversity of microbial communities in the
      biofilm that formed on the MES cathode. Specifically, the hydrogenotrophic
      methanogen Methanobacterium became the predominant archaea for methane production
      from CO2 reduction, while the abundance of the aceticlastic methanogen
      Methanosaeta decreased with increased temperature.

PMID- 29054075
TI  - Evaluation of immunological markers of ovine vaginal irritation: Implications for
      preclinical assessment of non-vaccine HIV preventive agents.
AB  - The presence of genital inflammatory responses and a compromised vaginal
      epithelial barrier have been linked to an increased risk of HIV acquisition. It
      is important to assure that application of candidate microbicides designed to
      limit HIV transmission will not cause these adverse events. We previously
      developed high resolution in vivo imaging methodologies in sheep to assess
      epithelial integrity following vaginal application of a model microbicide,
      however characterization of genital inflammation in sheep has not been previously
      possible. In this study, we significantly advanced the sheep model by developing
      approaches to detect and quantify inflammatory responses resulting from
      application of a nonoxynol-9-containing gel known to elicit vaginal irritation.
      Vaginal application of this model microbicide resulted in foci of disrupted
      epithelium detectable by confocal endomicroscopy. Leukocytes also infiltrated the
      treated mucosa and the number and composition of leukocytes obtained by
      cervicovaginal lavage (CVL) were determined by differential staining and flow
      cytometry. By 18h post-treatment, a population comprised predominantly of
      granulocytes and monocytes infiltrated the vagina and persisted through 44h post
      treatment. The concentration of proinflammatory cytokines and chemokines in CVL
      was determined by quantitative ELISA. Concentrations of IL-8 and IL-1beta were
      consistently significantly increased after microbicide application suggesting
      these cytokines are useful biomarkers for epithelial injury in the sheep model.
      Together, the results of these immunological assessments mirror those obtained in
      previous animal models and human trials with the same compound and greatly extend
      the utility of the sheep vaginal model in assessing the vaginal barrier and
      immune microenvironment.

PMID- 29054076
TI  - Genetic polymorphisms in angiogenesis-related genes are associated with worse
      progression-free survival of patients with advanced gastrointestinal stromal
      tumours treated with imatinib.
AB  - BACKGROUND: Imatinib 400 mg per day is first-line therapy for patients with
      gastrointestinal stromal tumours (GISTs). Although clinical benefit is high,
      progression-free survival (PFS) is variable. This study explores the relationship
      of single nucleotide polymorphisms (SNPs) in genes related to imatinib
      pharmacokinetics and pharmacodynamics and PFS in imatinib-treated patients with
      advanced GIST. METHODS: In 227 patients a pharmacogenetic pathway analysis was
      performed. Genotype data from 36 SNPs in 18 genes were tested in univariate
      analyses to investigate their relationship with PFS. Genetic variables which
      showed a trend (p < 0.1) were tested in a multivariate model, in which each
      singular SNP was added to clinicopathological factors. RESULTS: In univariate
      analyses, PFS was associated with synchronous metastases (p = 0.0008) and the
      mutational status (p = 0.004). Associations with rs1870377 in KDR (additive
      model, p = 0.0009), rs1570360 in VEGFA (additive model, p = 0.053) and rs4149117
      in SLCO1B3 (mutant dominant model, 0.027) were also found. In the multivariate
      model, significant associations and trends with shorter PFS were found for
      synchronous metastases (HR 1.94, p = 0.002), KIT exon 9 mutation (HR 2.45, p =
      0.002) and the SNPs rs1870377 (AA genotype, HR 2.61, p = 0.015), rs1570360 (AA
      genotype, HR 2.02, p = 0.037) and rs4149117 (T allele, HR 0.62, p = 0.083).
      CONCLUSION: In addition to KIT exon 9 mutation and synchronous metastases, SNPs
      in KDR, VEGFA and SLCO1B3 appear to be associated with PFS in patients with
      advanced GIST receiving 400-mg imatinib. If validated, specific SNPs may serve as
      predictive biomarkers to identify patients with an increased risk for progressive
      disease during imatinib therapy.

PMID- 29054077
TI  - Relationship between empathic processing and drinking behavior in project MATCH.
AB  - INTRODUCTION: Family relationships, social connectedness and a greater network of
      supportive others each predict better drinking outcomes among individuals with
      alcohol use disorder (AUD). The association between social factors and drinking
      may be related to the ability of individuals to take the perspectives of others'
      mental and emotional states, defined as empathic processing (EP). As such, it may
      be the case that EP is associated with social support (SS) and drinking behavior
      among individuals with AUD, yet few prior studies have attempted to define EP in
      an AUD sample. METHODS: The current study was a secondary data analysis of
      Project MATCH (N=1726) using structural equation modeling to model EP as a latent
      factor. The study also sought to test the baseline associations between EP, SS,
      and drinking behavior, as well as sex differences in the associations between EP,
      SS, and drinking. It was hypothesized that EP would be positively associated with
      SS and negatively associated with drinking behavior. RESULTS: Results suggested
      adequate model fit of the EP construct. Structural equation models indicated
      significant associations between EP, SS, and both drinking consequences and
      percent drinking days, but only for males. Males reported significantly lower EP
      and SS from friends, but more SS from family, compared to females. EP was not
      related to drinking among females. CONCLUSIONS: The current study validated a
      model of EP in a treatment-seeking sample of individuals with alcohol use
      disorder. Future work may consider EP as a treatment-modifiable risk factor for
      drinking frequency and consequences in males.

PMID- 29054078
TI  - Subacute oral toxicity assessment of benalaxyl in mice based on metabolomics
      methods.
AB  - In this study, the metabolic responses of mice after 30 days of exposure to
      benalaxyl were assessed using NMR-based untargeted metabolomics and LC-MS-based
      targeted profiling of 20 amino acids. Urinary 1H NMR analyses revealed
      alterations in energy metabolism, lipid metabolism, vitamin B metabolism, the
      urea cycle and amino acid metabolism, and targeted analyses indicated that the
      serum levels of asparagine, histidine, lysine and aspartic acid were
      significantly altered. Additionally, significant oxidative stress was observed in
      the liver and kidney, although no apparent histopathological injury was observed.
      The tissue distribution indicated a significant stereoselectivity in the brain,
      where (-)-R-benalaxyl was enriched. These data provide a comprehensive picture of
      the subacute toxic effects of benalaxyl in mice. The results of this study
      suggested that, for a toxicity evaluation, metabolomics analysis is much more
      sensitive than traditional toxicological methods. The results also highlight the
      combined use of untargeted and targeted metabolomics approaches in evaluating the
      health risks of xenobiotics.

PMID- 29054079
TI  - Synergic mechanism of adsorption and metal-free catalysis for phenol degradation
      by N-doped graphene aerogel.
AB  - 3D porous N-doped reduced graphene oxide (N-rGO) aerogels were synthesized by a
      hydrothermal reduction of graphene oxide (GO) with urea and following freeze
      drying process. N-rGO aerogels have a high BET surface of 499.70 m2/g and a high
      N doping content (5.93-7.46 at%) including three kinds of N (graphitic, pyridinic
      and pyrrolic). Their high catalytic performance for phenol oxidation in aqueous
      solution was investigated by catalytic activation of persulfate (PS). We have
      demonstrated that N-rGO aerogels are promising metal-free catalysts for phenol
      removal. Kinetics studies indicate that phenol degradation follows first-order
      reaction kinetics with the reaction rate constant of 0.16799 min-1 for N-rGO
      A(1:30). Interestingly, the comparison of direct catalytic oxidation with
      adsorption-catalytic oxidation experiments indicates that adsorption plays an
      important role in the catalytic oxidation of phenol by decreasing the phenol
      degradation time. Spin density and adsorption modeling demonstrates that
      graphitic N in N-rGO plays the most important role for the catalytic performance
      by inducing high positive charge densities to adjacent carbon atoms and
      facilitating phenol adsorption on these carbon sites. Furthermore, the activation
      mechanism of persulfate (PS) on N-rGO was first investigated by DFT method and PS
      can be activated to generate strongly oxidative radical (SO4.-) by transferring
      electrons to N-rGO.

PMID- 29054080
TI  - Efficient degradation of selected polluting dyes using the tetrahydroxoargentate
      ion, Ag(OH)4-, in alkaline media.
AB  - The use of soluble and highly oxidizing Ag(III) in the form of the
      tetrahydroxoargentate ion Ag(OH)4- is reported for the oxidation of surrogate
      organic recalcitrant dyes (i.e., rhodamine 6G (Rh6G) and fluorescein (Fl)). The
      possible use of Ag(OH)4- for the treatment of these and other refractory
      compounds is assessed. Such dyes were selected due to their common occurrence,
      stability, refractory nature, the relatively high toxicity of Rh6G, and their
      structural similarity to Fl. Several reaction intermediates/products were
      identified. The results showed that the highly oxidizing tetrahydroxoargentate
      anion was capable of degrading these recalcitrant dyes. Furthermore, the final
      degradation products do not represent a higher environmental risk than the
      original surrogates themselves. In addition, the partial mineralization of the
      dyes was proven.

PMID- 29054081
TI  - Reductive dehalogenation of DDT with folate models: Formation of the DDT
      metabolite spectrum under biomimetic conditions.
AB  - The insecticide DDT is an omnipresent environmental contaminant and an ongoing
      toxicological concern. The recent discovery that methylenetetrahydrofolate (MTHF)
      models are capable of reducing a range of halocarbons to hydrocarbons under
      biomimetic conditions has prompted us to investigate the possible role of MTHF in
      the metabolism of DDT. We now report that the reaction of MTHF models with DDT
      produces no less than five known in vivo metabolites of DDT, namely DDD, DDE,
      DDMU, DBP, and DDM. The capability of the MTHF models to produce the full
      spectrum of known DDT dehalogenation products is strong evidence that the
      mechanistically obscure metabolism of DDT may involve MTHF. The findings also
      suggest that DDT should be capable of disrupting folate-dependent pathways.

PMID- 29054082
TI  - Ecological risk assessment of coastal ecosystems: The case of mangrove forests in
      Hormozgan Province, Iran.
AB  - Sediment quality of mangrove forests in Hormozgan Province of Iran with a focus
      on two distinct habitats - the Hara Protected Area and the area of the Azini Bay 
      was studied. The accumulation of heavy metals in the sediments of the Hara
      Protected Area in terms of concentration was in the order of Pb > Zn > Cu > Cd
      and in those of the Azini Bay in the order of Zn > Cu > Pb > Cd. Based on
      Pearson's correlation coefficient, no significant correlations were found between
      concentrations of heavy metals in the sediments of the Hara Protected Area, while
      Zn and Pb concentrations were positively correlated in the sediments of the Azini
      Bay, implying a common pollution source. Common pollution indices, such as
      Contamination factor (Cf), degree of contamination (Cd), modified contamination
      degree (mCd), potential ecological risk index (RI) and metal pollution index
      (MPI), were used for assessing contamination status. The value of contamination
      (Cd) index was lower than 7 across all five stations of each studied region,
      implying a low degree of contamination. The modified contamination degree (mCd)
      index was lower than 1.5, showing that the sediment pollution was low in both
      regions. The potential ecological risk assessment index was 223.89 and 543.97 for
      the Hara Protected Area and the Azini Bay, respectively. Based on categorization
      of Hakanson's ecological risk, the Hara Protected Area region was in the range of
      150 <= RI <= 300 (moderate ecological risk) and the Azini Bay region in the range
      of 300 <= RI <= 600 (acceptable ecological risk). Findings raise awareness of the
      contamination status of mangrove forests in Hormozgan Province, provide a
      valuable benchmark for future comparisons in the area, and are important for the
      design of appropriate policies and long-term management of those ecosystems by
      local managers and the national authorities.

PMID- 29054083
TI  - Modulation of valence band maximum edge and photocatalytic activity of BiOX by
      incorporation of halides.
AB  - To better know the photocatalytic performance of bismuth oxyhalides (BiOX, X =
      Cl, Br, I) regulated by incorporation of halides within nanostructures, BiOX
      nanosheets were synthesized through morphology controllable solvothermal method
      and characterized systematically. The organic structural property greatly
      influences the photocatalytic activity of BiOX: 1) as for neutral molecular
      phenol, BiOX shows photocatalytic activity in the order of BiOCl > BiOBr > BiOI
      under simulated sun light irradiation, and the photo-oxidation kinetics follow
      Eley-Rideal mechanism; and 2) for adsorbed anionic orange II (OII) and cationic
      methylene blue (MB), BiOX shows photocatalytic activity in the order of BiOCl >
      BiOBr > BiOI, and the photo-oxidation kinetics follow Langmuir-Hinshelwood
      mechanism. The crystal structure of the catalyst also greatly influences the
      photocatalytic activity of BiOX: 1) The relative photo-oxidation power of O2*-
      radicals or HO radicals involved in this study were different which were
      quantitatively detected using typical radical trapping agent, separately; 2) The
      relative oxidation power of photogenerated holes (h+) in this study were in the
      order of BiOCl > BiOBr > BiOI, which may be ascribed to lowering the valence band
      maximum edge of BiOX through incorporation of halides as the atomic number of
      halides decreased. This study provides novel explanation for fabricating BiOX
      heterojunctions with tunable photocatalytic reactivity via regulating the halides
      ratio.

PMID- 29054084
TI  - Occurrence and levels of persistent organic pollutants (POPs) in farmed and wild
      marine fish from Tanzania. A pilot study.
AB  - In 2016, farmed and wild milkfish (Chanos chanos) and mullet (Mugil cephalus)
      from Tanzania mainland (Mtwara) and Zanzibar islands (Pemba and Unguja) were
      collected for analyses of persistent organic pollutants (POPs). Fish livers were
      analysed for organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs),
      brominated flame retardants (BFRs). Muscle tissue was used for analyses of
      perfluoroalkyl substances (PFASs). The major contaminant was p,p'-DDE. The
      highest p,p'-DDE concentration was found in wild milkfish from Mtwara (715.27
      ng/g lipid weight (lw)). This was 572 times higher than the maximum level
      detected in farmed milkfish from the same area. The ratios of p,p'-DDE/p,p'-DDT
      in wild milkfish and mullet from Mtwara and Pemba indicate historical use of DDT.
      In contrast, ratios in farmed milkfish from Unguja and Mtwara, suggest recent
      use. The levels of HCB, HCHs and trans-nonachlor were low. ?10PCBs levels were
      low, ranging from <LOD to 8.13 ng/g lw with the highest mean level found in
      farmed milkfish from Shakani, Unguja (3.94 ng/g lw). The PCB pattern was
      dominated by PCB -153 > -180> -138. PBDEs were detected in low and varying levels
      in all locations. BDE-47 was the dominating congener, and the highest level was
      found in farmed milkfish from Jozani (1.55 ng/g lw). HBCDD was only detected in
      wild mullet from Pemba at a level of 16.93 ng/g lw. PFAS was not detected in any
      of the samples. POP levels differed between geographic areas and between farmed
      and wild fish. Human activities seem to influence levels on PCBs and PBDEs on
      Unguja.

PMID- 29054085
TI  - Species-specific profiles and risk assessment of perfluoroalkyl substances in
      coral reef fishes from the South China Sea.
AB  - The contamination profiles of sixteen perfluoroalkyl substances (PFAS) were
      examined in coral reef fish samples collected from the South China Sea (SCS)
      where no information about this topic was available in the literature. The
      results revealed that six PFAS were found in coral reef fish samples from the
      SCS. Perfluorooctane sulfonate (PFOS) was the most predominant PFAS contaminant
      detected in most of the samples, with the highest concentration value of 27.05
      ng/g wet weight (ww) observed in Cephalopholis urodelus. Perfluoroundecanoic acid
      (PFUnDA) and Perfluorotridecanoic acid (PFTrDA) were the second and third
      dominant PFAS, respectively. Mean PFOS concentrations in muscle of seven coral
      reef fish varied from 0.29 ng/g ww in Lethrinus olivaceus to 10.78 ng/g ww in
      Cephalopholis urodelus. No significant linear relationship was observed between
      PFOS levels and coral reef fish traits (length, weight) collected in this region.
      Average daily intake of PFOS for the seven coral reef fishes ranged from 0.79
      ng/kg/d for Lethrinus olivaceus to 29.53 ng/kg/d for Cephalopholis urodelus. The
      hazard ratio (HR) values for human consumption of PFOS-contaminated coral reef
      fishes ranged from 0.04 to 1.48, with Cephalopholis urodelus having the highest
      HR value of 1.18 (higher than 1) among the species, indicating frequent
      consumption of Cephalopholis urodelus might pose potential health risk to local
      population. The present work have provided the first hand data of PFAS in coral
      reef fishes in the SCS and indirectly demonstrated the existence of low level
      PFAS pollution in the SCS in China.

PMID- 29054086
TI  - Are greenhouse gas emissions and cognitive skills related? Cross-country
      evidence.
AB  - Are greenhouse gas emissions (GHG) and cognitive skills (CS) related? We attempt
      to answer this question by exploring this relationship, using cross-country data
      for 150 countries, for the period 1997-2012. After controlling for the level of
      economic development, quality of political regimes, population size and a number
      of other controls, we document that CS robustly predict GHG. In particular, when
      CS at a national level increase by one standard deviation, the average annual
      rate of air pollution changes by nearly 1.7% (slightly less than one half of a
      standard deviation). This significance holds for a number of robustness checks.

PMID- 29054087
TI  - Using local knowledge and sustainable transport to promote a greener city: The
      case of Bucharest, Romania.
AB  - Cities undergoing climate change and rapid urbanization are faced with
      significant transformational processes that affect the environment and society,
      challenging them to become more sustainable and resilient. The promotion of
      nature-based solutions represents an efficient approach to meet sustainability
      targets in cities and improve the quality of life of citizens. The association of
      large components of green infrastructure, such as urban parks, with physical
      activity can counteract the sedentary lifestyle endemic to cities and improve the
      overall health and well-being of individuals (Carrus et al., 2013; Scopelliti et
      al., 2016). By promoting a sustainable means of transport and connecting green
      spaces within a highly urbanized city, bicycle lanes represent an effective tool
      for associating physical activity with nature in cities allowing bicycle users to
      benefit from the positive health effects of nature-based solutions. Our study
      focuses on the potential of bicycle lanes to improve functional connectivity
      among green spaces. We administered 820 questionnaires in 34 green spaces (i.e.,
      urban parks) in Bucharest, Romania, to identify the factors influencing the use
      of bicycle lanes connecting urban parks and to understand which planning criteria
      for bicycle lanes are considered as the most important by park visitors. We
      applied binary and ordinal logistic regressions and found that the factors
      affecting bicycle lane use are illegally parked cars and lack of accessibility to
      urban parks. The criteria preferred by park visitors for bicycle lane planning
      are determined by experience level and frequency of bicycle use. To develop a
      functional and integrated bicycle lane network that can make cities healthier and
      more sustainable, policy makers are advised to engage in a public participatory
      process and focus on the needs of bicycle users.

PMID- 29054088
TI  - The interactions among organophosphate pesticide exposure, oxidative stress, and
      genetic polymorphisms of dopamine receptor D4 increase the risk of attention
      deficit/hyperactivity disorder in children.
AB  - OBJECTIVE: The aim of this study was to clarify the association between
      organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder
      (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case
      control study enrolled 93 children with ADHD and 112 control children in north
      Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress
      biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4)
      were identified. RESULTS: Children with ADHD had significantly higher
      dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01)
      and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95ug/g cre. vs. 16.55ug/g
      cre., p value<0.01) concentrations than control children. Children who carried
      DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4
      GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The
      estimated value of the AP (attributable proportion due to interaction) was 0.59
      (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children
      with the DRD4 GG genotype were due to the gene-environment interaction. After
      adjustment for other covariates, children who carried the DRD4 GG genotype, had
      been exposed to high DMP levels (more than the median), and had high HNE-MA
      levels had a significantly increased risk for developing ADHD (OR = 11.74, 95%
      CI: 2.12-65.04). CONCLUSION: This study indicated a gene-environment interaction
      in the risk of ADHD in children. The association between DMP and ADHD in children
      might relate to the mechanism of lipid peroxidation. Dose-response relationships
      and the combined effects of OPs, oxidative stress, and genetic polymorphism on
      ADHD should not be neglected.

PMID- 29054089
TI  - Molecular characterization of Cryptococcus neoformans and Cryptococcus gattii
      from environmental sources and genetic comparison with clinical isolates in
      Apulia, Italy.
AB  - The present study investigated the environmental distribution of Cryptococcus
      neoformans and C. gattii species complex molecular types, mating types and
      sequence types in Apulia, a region of Southern Italy. A total of 2078 specimens
      from arboreal and animal sources were analyzed. The percentage of positive
      samples was similar among both arboreal and animal specimens: 4.2% vs. 5.1% for
      C. neoformans species complex and 0.6% vs. 1.4% for C. gattii species complex.
      Molecular typing identified 78 isolates as VNI (76 alphaA and two aA), one as AD
      hybrid alphaADa, and 16 as VGI aB. VNI isolates presented 10 different sequence
      types (STs) and VGI isolates two. The most frequent STs among C. neoformans and
      C. gattii species complex isolates were ST23 (51%) and ST156 (90%), respectively.
      Comparison with molecular types and STs results obtained from 21 clinical
      isolates collected in Apulia showed that one C. neoformans VNI clinical isolate
      shared an identical sequence type of one arboreal isolate (ST61) and that one C.
      gattii VGI clinical isolate matched with the main ST (ST156) present in the
      environment. In addition, molecular type VNIV was found only among clinical
      isolates and was absent in the investigated environmental area. In conclusion,
      the present study identified which C. neoformans and C. gattii species complex
      genotypes are circulating in Apulia, defined their ecological niches and revealed
      the relationship with clinical cases. It represents a basal study for addressing
      future investigations and public health interventions in the region.

PMID- 29054090
TI  - Diopside-magnetite; A novel nanocomposite for hyperthermia applications.
AB  - In the present work, the releasing heat, scaffold apatite formation, and magnetic
      behavior of a novel diopside-magnetite nanocomposite with various contents of
      magnetite (Fe3O4) were evaluated. The N'eel and Brown relaxations did not have a
      significant effect on the specific absorption rate (SAR) of the composite
      samples. Indeed, magnetic saturation, Ms, indicated a crucial effect on the heat
      release of the samples. The sample with 30wt% magnetite had the highest value of
      SAR, while the sample with 20wt% magnetite, in the form of scaffold, allowed the
      high amount of apatite formation on its surface.

PMID- 29054091
TI  - Early adolescents' body dysmorphic symptoms as compensatory responses to parental
      appearance messages and appearance-based rejection sensitivity.
AB  - Body dysmorphic disorder (BDD) is marked by high distress and behavioral and
      functional impairments due to preoccupation with perceived appearance anomalies.
      Our aim was to examine parental correlates of offspring's symptoms characteristic
      of BDD, testing both direct associations and indirect associations via appearance
      based rejection sensitivity (appearance-RS). Surveys were completed by 302
      Australian adolescents (9-14 years) and their parents. Findings indicated
      parents' weight and appearance teasing and child-report (but not parent-report)
      of parental negative attitudes about weight and appearance were uniquely
      associated with offspring's heightened BDD-like symptoms, and associations were
      partially indirect via adolescents' appearance-RS. Findings support theory that
      identifies parents as socializers of children's appearance concerns, and show
      that BDD-like symptoms may be partly elevated because of the mediating role of
      appearance-RS. We propose that BDD symptoms could partly emerge as compensatory
      responses to parents' appearance messages, and the associated bias to expect and
      perceive rejection based on one's appearance.

PMID- 29054092
TI  - Protein-mimicking nanoparticles for the reproduction of transient protein
      receptor interactions.
AB  - One of the major concerns in target identification has been the need for new
      methods to detect target molecules in the native cellular environment. In
      conventional target identification, affinity-based pull down has been conducted
      using cell lysates. However, interactions in cell lysate do not reflect real
      endogenous interactions in living cells, and can produce false-positive or false
      negative results. This study aimed to develop a new method of target protein
      identification in living cells. Targeting probes were conjugated onto magnetic
      nanoparticles (MNPs). After nanoparticle cellular uptake, identification and
      recruitment of target proteins were conducted in living cells, and the target
      protein was finally recovered under the magnetic field. As a proof-of-concept
      study, we developed a functionalized MNP (PTS1-MNP) to mimic a peroxisomal
      protein containing a synthetic peroxisomal targeting signal 1 (PTS1). The PTS1
      MNPs were imported into human hepatoma HepG2 cells to recruit PTS1-receptor
      protein Pex5p. Successful peroxisomal translocation of PTS-MNPs was achieved via
      transient interaction with Pex5p. Pull-down of Pex5p in lysed or living HepG2
      cells confirmed the selective recruiting functionality of synthetic PTS1. The
      specific detection of Pex5p before complete PTS1-MNPs translocation in living
      HepG2 cells further demonstrated the transient interaction between Pex5p and PTS1
      MNPs. This is the first report showing the peroxisomal translocation of
      nanostructured materials in living cells. This approach can be applied as a new
      concept to study transient interactions and target identification or recruiting
      in living cells.

PMID- 29054093
TI  - The role of pazopanib on tumour angiogenesis and in the management of cancers: A
      review.
AB  - Pazopanib is a relatively new compound to be introduced into the chemotherapy
      field. It is thought to have decent anti-angiogenic properties, which gives an
      additional hope for the treatment of certain types of cancers. A systematic
      review solely discussing about pazopanib and its anti-angiogenic effect is yet to
      be published to date, despite several relevant clinical trials being conducted
      over the recent years. In this review, we aim to investigate the mechanism of
      pazopanib's anti-angiogenic effect and its effectiveness in treating several
      cancers. We have included, in this study, findings from electronically searchable
      data from randomized clinical trials, clinical studies, cohort studies and other
      relevant articles. A total of 352 studies were included in this review. From the
      studies, the effect of pazopanib in various cancers or models was observed and
      recorded. Study quality is indefinite, with a few decent quality articles. The
      most elaborately studied cancers include renal cell carcinoma, solid tumors,
      advanced solid tumors, soft tissue sarcoma, breast cancer and gynecological
      cancers. In addition, several less commonly studied cancers are included in the
      studies as well. Pazopanib had demonstrated its anti-angiogenic effect based on
      favorable results observed in cancers, which are caused by angiogenesis-related
      mechanisms, such as renal cell carcinoma, solid tumors, advanced solid tumors and
      soft tissue sarcoma. This review was conducted to study, analyze and review the
      anti-angiogenic properties of pazopanib in various cancers. The results obtained
      can provide a decent reference when considering treatment options for
      angiogenesis-related malignancies. Furthermore, the definite observations of the
      anti-angiogenic effects of pazopanib could provide newer insights leading to the
      future development of drugs of the same mechanism with increased efficiency and
      reduced adverse effects.

PMID- 29054094
TI  - RUNX3 inhibits the proliferation and metastasis of gastric cancer through
      regulating miR-182/HOXA9.
AB  - OBJECTIVE: This study intended to explore the molecular mechanism of RUNX3 in
      inhibiting the process of migration and proliferation of gastric cancer (GC)
      cells. METHODS: The overexpressed plasmids of RUNX3 and the interfering siRNA of
      RUNX3 were transfected into GC cells. Then, qRT-PCR and western blot were
      performed to identify the expression level of RUNX3 and miR-182 in tumors and
      adjacent tissues respectively. ChIP and luciferase assay were performed to detect
      the relationship between RUNX3 and miR-182 as well as miR-182 and HOXA9.
      Furthermore, EdU assay were used to investigate the proliferation of GC cells,
      Transwell assay and wound healing assay were utilized to assess cell metastasis.
      Xenograft mouse model was set to evaluate the proliferation in vivo. RESULTS: The
      results of qRT-PCR and western blot indicated that RUNX3 could regulate the
      expression of miR-182. RUNX3 can be straightly interacted with the promoter
      region of miR-182 in accordance with the results of ChIP. Luciferase assay
      revealed that HOXA9 was the direct target gene of miR-182. In addition, EdU
      proliferation, wound healing assay and transwell assay showed that miR-182 mimics
      and HOXA9 siRNA could inhibit the ability of cells proliferation, migration and
      invasion. The findings of in vivo experiments strongly supported the view that
      miR-182/HOXA9 was involved in the process of RUNX3-mediated GC tumor growth.
      CONCLUSIONS: RUNX3 could impede the ability of GC cells proliferation, migration
      and invasion by modulating miR-182/HOXA9 pathway.

PMID- 29054095
TI  - Ginkgolide B and bilobalide ameliorate neural cell apoptosis in alpha-synuclein
      aggregates.
AB  - The accumulation of aggregated forms of the alpha-Synuclein (alpha-Syn) is
      associated with the pathogenesis of Parkinson's disease (PD), a chronic
      progressive neurodegenerative disorder. Extensive evidences have shown the
      promising effects of Ginkgo biloba consumption on motor activity after PD.
      However, the mechanisms underline the alpha-Syn-induced cell damage and whether
      ginkgolides exert neuroprotection against this injury are unclear. Here we showed
      that aggregated recombinant human alpha-Syn, but not alpha-Syn monomers,
      triggered cell injury in cultured human neuroblastoma cell line SH-SY5Y in an
      apoptosis way by using flow cytometry and western blot assay. Moreover, pre
      treatment with the Ginkgolide B (GB) or Bilobalide (BB) protected SH-SY5Y cells
      against alpha-Syn-induced cell viability decreases, and reduced cell apoptosis
      after aggregated alpha-Syn stimulation. Together, we firstly find that aggregated
      alpha-Syn induced cell apoptosis and GB and BB may attenuate aggregated alpha-Syn
      induced cell apoptosis, which gives us an insight into the novel therapy for PD
      in future.

PMID- 29054096
TI  - Simplified AutoDock force field for hydrated binding sites.
AB  - A set of high quality structures of protein-ligand complexes with experimentally
      determined binding affinities has been extracted from the Protein Data Bank and
      used to test and recalibrate AutoDock force field. Since for some binding sites
      water molecules are crucial for bridging the receptor-ligand interactions, they
      have to be included in the analysis. To simplify the process of incorporating
      water molecules into the binding sites and make it less ambiguous, new simple
      water model was created. After recalibration of the force field on the new
      dataset much better correlation between the computed and experimentally
      determined binding affinities was achieved and the quality of pose prediction
      improved even more.

PMID- 29054098
TI  - Computational study to understand the energy transfer pathways within amicyanin.
AB  - Vibrational energy diffusivities between the residues present in Amicyanin copper
      protein are calculated and presented in form of communication map. From those
      results energy flow pathways from the copper metal ion to the inter protein
      residue Glu31 are identified. Our finding suggests many different pathways are
      possible and copper metal ion in oxidized and reduced state switches the
      pathways. Our finding also suggests the cooperative nature of surrounding
      residues and water molecules towards selecting the pathways. The major transport
      channels in the oxidised state are, Cu2+---> MET28---> LYS29---> TYR30---> GLU31
      and Cu2+---> MET98---> TYR30--- > GLU31. And in the reduced state Cu+---> CYS9--
      > TYR30---> GLU31 and Cu+---> MET28---> LYS2---> TYR30---> GLU31. We studied
      further the interaction energies between the copper ion and neighbouring residues
      using B3LYP/QZVP method. Both the methods complement each other in predicting the
      energy flow pathways and the cooperative nature of residues.

PMID- 29054097
TI  - Dynamic characteristics of a flagellar motor protein analyzed using an elastic
      network model.
AB  - At the base of a flagellar motor, its rotational direction and speed are
      regulated by the interaction between rotor and stator proteins. A switching event
      occurs when the cytoplasmic rotor protein, called C-ring, changes its
      conformation in response to binding of the CheY signal protein. The C-ring
      structure consists of FliG, FliM, and FliN proteins and its conformational
      changes in FliM and FliG including HelixMC play an important role in switching
      the motor direction. Therefore, clarifying their dynamic properties as well as
      conformational changes is a key to understanding the switching mechanism of the
      motor protein. In this study, to elucidate dynamic characteristics of the C-ring
      structure, both harmonic (intrinsic vibration) and anharmonic (transition
      pathway) analyses are conducted by using the symmetry-constrained elastic network
      model. As a result, the first three normal modes successfully capture the essence
      of transition pathway from wild type to CW-biased state. Their cumulative square
      overlap value reaches up to 0.842. Remarkably, it is also noted from the
      transition pathway that the cascade of interactions from the signal protein to
      FliM to FliG, highlighted by the major mode shapes from the first three normal
      modes, induces the reorientation (~100 degrees  rotation of FliGC5) of FliG C
      terminal that directly interacts with the stator protein. Presumably, the
      rotational direction of the motor protein is switched by this substantial change
      in the stator-rotor interaction.

PMID- 29054099
TI  - Examining factors associated with elevated Lie Scale responding on the Child
      Abuse Potential Inventory.
AB  - Child maltreatment remains a serious public health issue in the United States.
      Therefore, it is important to engage in quality control of the assessment,
      prevention, and treatment services for families affected by maltreatment.
      Parenting capacity assessments (PCAs) are typically an integral part of service
      delivery for families affected by maltreatment and can carry serious consequences
      for the referred parent. The Child Abuse Potential Inventory (CAPI) is a measure
      that is widely used in PCAs; however, socially desirable responding on the CAPI
      can serve to invalidate the important information derived from this assessment,
      as well as lead to negative impressions of the parent. Using data collected via
      multiple methods (including a non-face valid behavioral measure, intelligence
      screening, and self-report) from a predominantly at-risk sample of parents, the
      aim of this study was to better understand factors that may predict socially
      desirable responding on the CAPI. Results indicated that lower parental
      intelligence, a "positivity bias" (i.e., the tendency to learn and attend to
      positive over negative information during the non-face valid behavioral task),
      and lower reported depressive symptoms were associated with higher socially
      desirable responding. These findings suggest that assessors should thoughtfully
      consider the possibility that invalid CAPI scores may be more related to low
      intelligence and a positivity bias than to psychopathy and manipulation (e.g.,
      purposefully trying to present oneself in a positive light to gain favor in a
      PCA).

PMID- 29054100
TI  - Recovery-Based Interprofessional Distance Education (RIDE): Graduate Student
      Responses.
AB  - Graduate student attitudes (n = 28) were assessed before and after participation
      in interprofessional practitioner education (IPE). Twenty-eight graduate students
      participated (14 mental health nursing, 6 pharmacy, 4 nutrition, 4 exercise
      physiology); most had at least some health care experience. Posttest scores
      indicated gains on a majority of constructs measured. These results suggest that
      online-blended IPE content yields gains in team skills and attitudes. This study
      adds to a very small body of literature on IPE in graduate programs. More
      research is needed in examining online versus face-to-face delivery.

PMID- 29054101
TI  - Virtual Simulated Care Coordination Rounds for Nursing Students.
AB  - Implementation of the Affordable Care Act has nursing education reflecting on
      paradigm shifts in order to prepare nursing students for the evolving health care
      environment. The traditional focus of nursing education on nursing care in acute
      care settings does not provide learning experiences in care coordination and
      transitional care management skills. Virtual simulated care coordination rounds,
      using the National League for Nursing Advancing Care Excellence resources, offer
      nursing students an innovative experience in care coordination and transition
      care management.

PMID- 29054102
TI  - Supporting Faculty During Pedagogical Change Through Reflective Teaching
      Practice: An Innovative Approach.
AB  - Given the recent calls for transformation of nursing education, it is critical
      that faculty be reflective educators. Reflective teaching practice is a process
      of self-examination and self-evaluation to gain insight into teaching to improve
      the teaching-learning experience. Limited attention has been given to this notion
      in the nursing education literature. An innovative reflective teaching practice
      approach for nursing education is proposed, consisting of question cues,
      journaling, and a process of facilitated meetings. The authors describe their
      perceptions of using this approach with faculty during the implementation of a
      new pedagogy and suggest areas for further research.

PMID- 29054103
TI  - Preparedness Education in the Baccalaureate Nursing Curriculum: An Authentic
      Clinical Experience.
AB  - Healthy People 2020 supports the preparation of nurse graduates to assess
      emergency preparedness needs of defined populations and includes preparedness as
      one of its objectives. Natural disaster preparedness is addressed through the
      lens of community-centered care that meets the Quality and Safety Education for
      Nurses domains of patient-centered care and teamwork and collaboration. This
      article discusses the development of an authentic clinical experience through
      collaboration between the American Red Cross and a baccalaureate nursing program.

PMID- 29054104
TI  - Integrating Gerontology and Community Concepts Through Simulation.
AB  - This article describes an innovative simulation experience for nursing students.
      Faculty from a community health nursing course and a course in gerontology worked
      together to provide a comprehensive simulation experience that combined low
      fidelity and high-fidelity experiences that provided an integrated learning
      experience and gave faculty with an opportunity to collaborate to improve
      outcomes. Student and faculty feedback was overwhelmingly positive. Future plans
      include incorporating a third didactic course, Leadership and Management, and
      working with other disciplines to demonstrate interprofessional collaboration.

PMID- 29054105
TI  - Getting Social: The Use of Social Media to Improve Alumni Response Rates for
      Assessment of Program Outcomes.
AB  - Outcome assessment has become standard in institutions of higher learning and is
      a requirement of State Boards of Nursing and major accrediting bodies, including
      all accrediting agencies for programs in nursing. Appropriate identification of
      student learning outcomes and program outcomes to ensure the collection of
      relevant and meaningful data is essential. Although much has been written about
      what should be included in assessment, little information exists on how to best
      collect the required data for evaluation. This article describes an innovative
      approach to improving alumni response rates to assess program outcomes through
      the use of social media.

PMID- 29054106
TI  - Age of diagnosis, incidence and prevalence of recurrent respiratory
      papillomatosis-A South African perspective.
AB  - OBJECTIVES: To determine the distribution of the age of diagnosis of recurrent
      respiratory papillomatosis (RRP) and to determine the incidence and prevalence of
      RRP in both adults and children in the Free State province of South Africa in
      order to provide data from a population in sub-Saharan African. DESIGN:
      Retrospective record review. PARTICIPANTS: All patients with RRP in the Free
      State province of South Africa between 2011 and 2015. MAIN OUTCOME MEASURES:
      Distribution of the age of diagnosis of RRP and incidence and prevalence of RRP.
      RESULTS: The best fitting mixture distribution for the age of diagnosis of RRP
      was a two-component mixture of log-normal distributions. Within the first
      component (JoRRP), the age of diagnosis was significantly lower in patients with
      human papillomavirus (HPV)11 disease (median 3.2 year) than those with HPV6
      disease (median 5.6 years) (P = .021), while in the second component (AoRRP),
      there was no significant difference in the age of diagnosis between HPV11 disease
      (30.7 year) and HPV6 disease (median 44.0 years) (P = .0696). The incidence and
      prevalence of JoRRP were 1.34/100000 population/year and 3.88/100000 population,
      respectively, while the incidence and prevalence of AoRRP were 0.18/100000
      population/year and 0.38/100000 population, respectively. CONCLUSION: Recurrent
      respiratory papillomatosis in the Free State province of South Africa is a
      disease with a predominantly juvenile onset, with AoRRP having a lower prevalence
      than in Europe. This is probably reflective of the situation in sub-Saharan
      Africa.

PMID- 29054107
TI  - Characterisation of flower colouration in 30 Rhododendron species via anthocyanin
      and flavonol identification and quantitative traits.
AB  - Floral colour is a key reproductive character, often associated with
      environmental adaptation, and subject to human intervention. A large number of
      Rhododendron species differ widely in flower colour, providing a good model for
      flower colouration. The chromatic features and anthocyanin compositions of 30
      species from seven subgenera were systematically analysed. The Royal
      Horticultural Society Colour Chart and CIE L*a*b* system were employed to
      describe and investigate flower colours. The UPLC-PDA/ESI-MSn system was used to
      identify and quantify anthocyanins in petal extracts. The flower colours of 30
      Rhododendron species were categorised into four groups - red, purplish pink,
      purple and white. Seven anthocyanins were identified and quantified in petals:
      delphinidin, cyanidin and malvidin 3-O-arabinoside-5-O-glucosides, cyanidin 3,5
      di-O-glucoside, 3-O-galactoside and 3-O-arabinoside, and delphinidin 3-O
      glucoside. The red-flowered species mainly contained cyanidin monoglycosides and
      had much higher total anthocyanin content than purplish pink- and purple-flowered
      species. Purplish pink- and purple-flowered species had similar anthocyanin types
      and content. The chromatic differences were significant among groups, except the
      purplish pink and purple groups. Statistical analysis showed that Cy3Gal and
      Cy3Arb are characteristic for red-flowered species, and Mv3Arb5G and Dp3Arb5G
      play important roles in purple colouration; their contents were major components
      that greatly affected the chromatic parameters. In total, 21 flavonol derivates
      were identified. However, total flavonol content and co-pigmentation index showed
      no significant difference or correlation among/with colour groups, suggesting
      that flavonols might not play a major role in colouration. These results enhance
      our knowledge of the biochemical basis of flower colouration in Rhododendron
      species, and provide a foundation for genetic variation studies and aid in
      breeding cultivars with novel flower colours.

PMID- 29054108
TI  - Increase in proapoptotic activity of inhibitory PAS domain protein via
      phosphorylation by MK2.
AB  - Inhibitory PAS domain protein (IPAS) is a bifunctional protein that downregulates
      hypoxic gene expression and exerts proapoptotic activity by preventing
      prosurvival activity of Bcl-xL and its related factors. Proapoptotic activity of
      IPAS is attenuated by the activation of the PINK1-Parkin pathway, and involved in
      neuronal degeneration in an experimental mouse model of Parkinson's disease. The
      current study shows that phosphorylation of IPAS at Ser184 by MAPK-activated
      protein kinase 2 (MK2 or MAPKAPK2) enhances the proapoptotic function of IPAS.
      Perinuclear clustering of mitochondria and activation of caspase-3 caused by the
      transient expression of EGFP-IPAS were increased by UVB irradiation. The C
      terminal region of IPAS mediated the UVB susceptibility of IPAS. Increase in IPAS
      induced mitochondrial clustering by UVB was completly inhibited by the p38 MAPK
      inhibitor SB203580. Mass spectrometry analysis of UVB-activated IPAS identified
      several phosphorylation sites in the C-terminal region containing p38 MAPK
      consensus phosphorylation sites at Ser219 and Ser223, and an MK2 consensus site
      at Ser184. Although mutations of Ser219 and Ser223 to Ala did not suppress the
      UVB-induced mitochondrial clustering, replacement of Ser184 with Ala blocked it.
      A phosphomimetic substitution at Ser184 enhanced mitochondrial clustering and
      activation of caspase-3 without UVB exposure. Furthermore, binding affinity to
      Bcl-xL was increased by the mutation. Treatment of PC12 cells with CoCl2 caused
      activation of MK2 and mitochondrial clustering. IPAS-dependent cell death induced
      by CoCl2 in PC12 cells was decreased by the treatment with the MK2 inhibitor MK2
      inhibitor III and by siRNA-directed silencing of MK2.

PMID- 29054109
TI  - Influence of backside loading on the floating mass transducer: An in vitro
      experimental study.
AB  - HYPOTHESIS: The vibration of the floating mass transducer (FMT) of a single
      active middle-ear implant (AMEI) is distinctly influenced by the properties of
      the material coupled to its back side. BACKGROUND: In round window vibroplasty,
      the FMT needs to be padded against the surrounding bone opposite from the round
      window membrane. This represents one factor influencing its performance as a
      round window driver. Therefore, we examined the effects of different materials
      linked to the back side of an FMT on its vibration range. METHODS: The back side
      of an FMT was glued to a silicone cylinder 1.0 mm in diameter and 1.0 mm - 1.5 mm
      in length and of 40A, 50A or 70A Shore hardness; to cartilage of equivalent size;
      or to a round window soft coupler (RWSC), all firmly fixed on a steel plate. The
      vibrations were determined by a laser Doppler vibrometer (LDV) measuring the
      velocity of the centre point on the front side of the FMT. RESULTS: The materials
      on the back side of the FMT significantly influenced the vibration range of the
      FMT. The RWSC and silicone of 40A Shore hardness allowed for the highest detected
      velocities, while cartilage led to a distinct reduction similarly to 70A
      silicone. CONCLUSION: The coupling on the back side of an FMT distinctly affects
      its vibration range. In this regard, the RWSC and silicone of 40A Shore hardness
      yield the least impairment of vibration. Thus, the RWSC may be a feasible option
      in round window vibroplasty when additionally connected to the FMT opposite from
      the round window membrane.

PMID- 29054110
TI  - Mortality burden from seasonal influenza and 2009 H1N1 pandemic influenza in
      Beijing, China, 2007-2013.
AB  - BACKGROUND: Data about influenza mortality burden in northern China are limited.
      This study estimated mortality burden in Beijing associated with seasonal
      influenza from 2007 to 2013 and the 2009 H1N1 pandemic. METHODS: We estimated
      influenza-associated excess mortality by fitting a negative binomial model using
      weekly mortality data as the outcome of interest with the percent of influenza
      positive samples by type/subtype as predictor variables. RESULTS: From 2007 to
      2013, an average of 2375 (CI 1002-8688) deaths was attributed to influenza per
      season, accounting for 3% of all deaths. Overall, 81% of the deaths attributed to
      influenza occurred in adults aged >=65 years, and the influenza-associated
      mortality rate in this age group was higher than the rate among those aged <65
      years (113.6 [CI 49.5-397.4] versus 4.4 [CI 1.7-18.6] per 100 000, P < .05). The
      mortality rate associated with the 2009 H1N1 pandemic in 2009/2010 was comparable
      to that of seasonal influenza during the seasonal years (19.9 [CI 10.4-33.1] vs
      17.2 [CI 7.2-67.5] per 100 000). People aged <65 years represented a greater
      proportion of all deaths during the influenza A(H1N1)pdm09 pandemic period than
      during the seasonal epidemics (27.0% vs 17.7%, P < .05). CONCLUSIONS: Influenza
      is an important contributor to mortality in Beijing, especially among those aged
      >=65 years. These results support current policies to give priority to older
      adults for seasonal influenza vaccination and help to define the populations at
      highest risk for death that could be targeted for pandemic influenza vaccination.

PMID- 29054111
TI  - Dipeptidyl peptidase 4 inhibitors attenuates the decline of skeletal muscle mass
      in patients with type 2 diabetes.
AB  - BACKGROUND: Activation of dipeptidyl peptidase 4 has been reported to be
      associated with impairment of insulin signalling in skeletal muscle, presumably
      leading to loss of muscle function. This study was aimed to investigate whether
      the use of dipeptidyl peptidase 4 inhibitors (DPP4i) could attenuate the
      progressive loss of muscle mass in patients with type 2 diabetes. METHODS: A
      total 105 patients with type 2 diabetes (mean age 62 +/- 12 years; 39% female)
      were studied in this retrospective observational study. To reduce the bias due to
      confounding variables, propensity-score matching analysis was performed. Change
      in skeletal muscle index measured by the whole body dual-energy X-ray
      absorptiometry at 1-year follow-up was evaluated. One-year changes in visceral
      and subcutaneous fat area and liver attenuation index were also determined by
      abdominal computed tomography. RESULTS: Overall, 37 of 105 (35.2%) patients were
      treated with DPP4i. The estimated change in skeletal muscle index in patients
      with DPP4i was significantly higher than that in patients without (0.05 +/- 0.06
      vs -0.10 +/- 0.04 kg, P = .046). In a propensity-matched population (N = 48), the
      same finding was observed (0.04 +/- 0.03 in DPP4i versus -0.12 +/- 0.03 kg in non
      DPP4i, P = .033). There were no significant differences in changes of visceral
      and subcutaneous fat area and liver attenuation index between patients with DPP4i
      and those without. CONCLUSIONS: Our data suggest the potential of DPP4i to
      prevent the progressive loss of muscle mass with ageing in patients with type 2
      diabetes.

PMID- 29054113
TI  - Post-operative corticosteroid irrigation for chronic rhinosinusitis after
      endoscopic sinus surgery: A meta-analysis.
AB  - BACKGROUND: Recently, topical steroid therapy delivery using high-volume
      sinonasal irrigations has been used more frequently, following endoscopic sinus
      surgery (ESS), to improve drug delivery into the paranasal sinuses. OBJECTIVE:
      The goal of this study was to perform a systematic review with meta-analysis of
      the efficacy of steroid nasal irrigation on post-operative management of Chronic
      rhinosinusitis (CRS) following ESS. METHODS: Five databases (PubMed, SCOPUS,
      Embase, Web of Science, and the Cochrane database) from inception to March 2017
      were independently reviewed by two researchers. Studies that scored CRS
      endoscopic findings and CRS-related quality of life (QOL) post-operatively before
      and after steroid nasal irrigation and that compared the effects of steroid nasal
      irrigation (treatment groups) with saline alone irrigation (control group) were
      included in the analysis. RESULTS: Twelve studies (n = 360) met inclusion
      criteria. Steroid nasal irrigation significantly reduced the endoscopic score
      compared with pre-treatment values and also improved QOL. Adverse effects
      following steroid nasal irrigation such as increased intraocular pressure (IOP)
      and hypothalamus-pituitary-adrenal (HPA) axis disturbance were not significant.
      However, compared with saline alone irrigation, the additional effects of steroid
      irrigation were not significant in the view of the endoscopic score and disease
      specific QOL. CONCLUSION: Although steroid nasal irrigation would not induce
      adverse effects related to systemic steroid absorption, the beneficial effects of
      additional steroids in saline irrigation were ambiguous in regard to endoscopic
      score and CRS-related QOL improvement compared with saline alone irrigation.
      However, further clinical trials with robust research methodologies should be
      conducted to confirm the results of this study.

PMID- 29054112
TI  - Human parainfluenza virus infection in severe acute respiratory infection cases
      in Beijing, 2014-2016: A molecular epidemiological study.
AB  - BACKGROUND: Severe acute respiratory infection (SARI) threatens human health and
      even survival, causing a huge number of hospitalized patients every year.
      However, as one of the most common respiratory viruses circulated worldwide, the
      epidemiological and phylogenetic characteristics of human parainfluenza virus
      (HPIV) in these cases were not well known. OBJECTIVES: To reveal the
      epidemiological features of HPIV infection in SARIs in Beijing area from
      September 2014 to August 2016. METHODS: A total of 1229 SARI cases in Beijing
      area were enrolled, investigated, sampled, and tested by multiplex real-time PCR
      to identify HPIVs and other common respiratory viruses. Eighteen HPIV-3 viruses
      isolated from all HPIV-positive samples in these SARI cases were sequenced and
      analyzed. RESULTS: Among all enrolled cases, 0.81%, 0.73%, 4.48%, and 0.57% were
      positive for HPIV-1 to HPIV-4, respectively. The highest yield rate of HPIV
      infection occurred in children under 5 years old (9.07%), followed by the
      patients over 60 years old (6.02%). The phylogenetic information of HPIV-3 showed
      that all viruses belonged to Cluster C3a. CONCLUSIONS: Besides the young
      children, the elders older than 60 years also showed a relatively high infection
      rate of HPIVs, which should be given comparable attentions. Moreover, the HPIV-3
      circulating in China undergoes continued evolution, suggesting the potential risk
      of evolved HPIV infection should not be overlooked.

PMID- 29054114
TI  - Characterization of melanosomes and melanin in Japanese patients with Hermansky
      Pudlak syndrome types 1, 4, 6, and 9.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized
      by oculocutaneous albinism (OCA), a bleeding tendency, and ceroid deposition.
      Most of the causative genes for HPS encode subunits of the biogenesis of lysosome
      related organelles complex (BLOC). In this study, we identified one patient each
      with HPS4, HPS6, and HPS9 by whole-exome sequencing. Next, we analyzed hair
      samples from the three patients and representative patients with HPS1 and
      controls using electron microscopy and chemical methods. All HPS patients had
      fewer, smaller, and more immature melanosomes than healthy controls. Further, all
      patients showed reduced total melanin content and increased levels of
      benzothiazine-type pheomelanin. The results of this study demonstrate the impact
      of the dysfunctions of BLOCs on the maturation of melanosomes and melanin levels
      and composition through analysis of their hair samples.

PMID- 29054115
TI  - Reversible mono-ADP-ribosylation of DNA breaks.
AB  - Adenosine diphosphate (ADP)-ribosylation is a chemical modification of
      macromolecules that plays an important role in regulation of quintessential
      biological processes such as DNA repair, transcription, chromatin remodelling,
      stress response, apoptosis, bacterial metabolism and many others. ADP
      ribosylation is carried out by ADP-ribosyltransferase proteins, such as poly (ADP
      ribose) polymerases (PARPs) that transfer either monomer or polymers of ADP
      ribose onto the molecular targets by using nicotinamide adenine dinucleotide
      (NAD+ ) as a cofactor. Traditionally, proteins have been described as primary
      targets of ADP-ribosylation; however, there has been growing evidence that DNA
      may be a common target as well. Here, we show using biochemical studies that
      PARP3, a DNA damage-activated ADP-ribosyltransferase, can mono-ADP-ribosylate
      double-stranded DNA ends. ADP-ribosylation of DNA mediated by PARP3 attaches a
      single mono-ADP-ribose moiety to the phosphate group at the terminal ends of DNA.
      We further show that mono ADP-ribosylation at DNA ends can be efficiently
      reversed by several cellular hydrolases (PARG, MACROD2, TARG1 and ARH3). This
      suggests that mono ADP-ribosylated DNA adducts can be efficiently removed in
      cells by several mechanisms.

PMID- 29054117
TI  - Assessing global range expansion in a cryptic species complex: insights from the
      red seaweed genus Asparagopsis (Florideophyceae).
AB  - The mitochondrial genetic diversity, distribution and invasive potential of
      multiple cryptic operational taxonomic units (OTUs) of the red invasive seaweed
      Asparagopsis were assessed by studying introduced Mediterranean and Hawaiian
      populations. Invasive behavior of each Asparagopsis OTU was inferred from
      phylogeographic reconstructions, past historical demographic dynamics, recent
      range expansion assessments and future distributional predictions obtained from
      demographic models. Genealogical networks resolved Asparagopsis gametophytes and
      tetrasporophytes into four A. taxiformis and one A. armata cryptic OTUs.
      Falkenbergia isolates of A. taxiformis L3 were recovered for the first time in
      the western Mediterranean Sea and represent a new introduction for this area.
      Neutrality statistics supported past range expansion for A. taxiformis L1 and L2
      in Hawaii. On the other hand, extreme geographic expansion and an increase in
      effective population size were found only for A. taxiformis L2 in the western
      Mediterranean Sea. Distribution models predicted shifts of the climatically
      suitable areas and population expansion for A. armata L1 and A. taxiformis L1 and
      L2. Our integrated study confirms a high invasive risk for A. taxiformis L1 and
      L2 in temperate and tropical areas. Despite the differences in predictions among
      modelling approaches, a number of regions were identified as zones with high
      invasion risk for A. taxiformis L2. Since range shifts are likely climate-driven
      phenomena, future invasive behavior cannot be excluded for the rest of the
      lineages.

PMID- 29054118
TI  - Efficacy of laryngectomy alone for treatment of locally advanced laryngeal
      cancer: A stage- and subsite-specific survival analysis.
AB  - OBJECTIVE: Total laryngectomy is a well-established treatment for locally
      advanced laryngeal cancer. Evidence for the benefit of post-operative
      radiotherapy after laryngectomy in patients with locally advanced primaries and
      N0 or N1 nodal disease is limited. This study aimed to determine whether total
      laryngectomy alone is adequate therapy for certain patient subgroups with locally
      advanced laryngeal cancer. DESIGN: We performed a retrospective survival analysis
      of patients in the surveillance epidemiology and end results (SEER) database with
      locally advanced laryngeal cancer between 2004 and 2012. OUTCOME MEASURES:
      Primary outcome measure was overall survival. RESULTS: For all patients with T3
      4aN0-1 tumours, overall survival was worse for those treated with laryngectomy
      only when compared using the Kaplan-Meier with a log-rank test and when
      accounting for demographic and tumour data using a Cox multivariate regression.
      Other independent predictors of poor survival included age >65 years old,
      Medicaid or uninsured payor status, supraglottic primary and N1 nodal disease.
      Stage- and subsite-specific analysis revealed that patients with T4a primary
      tumours, N1 nodal disease and supraglottic subsite had worse overall survival
      when treated with laryngectomy alone. Alternatively, patients with T3 primary
      tumours, N0 nodal disease, glottic subsite had equivalent overall survival and
      disease-specific survival when treated with laryngectomy alone vs laryngectomy
      with post-operative radiotherapy. CONCLUSION: Locally advanced laryngeal cancer
      patients with T3 primaries, no nodal disease or primaries of the glottis may not
      benefit from post-operative radiotherapy when treated with primary total
      laryngectomy.

PMID- 29054116
TI  - T-cell epitope content comparison (EpiCC) of swine H1 influenza A virus
      hemagglutinin.
AB  - BACKGROUND: Predicting vaccine efficacy against emerging pathogen strains is a
      significant problem in human and animal vaccine design. T-cell epitope cross
      conservation may play an important role in cross-strain vaccine efficacy. While
      influenza A virus (IAV) hemagglutination inhibition (HI) antibody titers are
      widely used to predict protective efficacy of 1 IAV vaccine against new strains,
      no similar correlate of protection has been identified for T-cell epitopes.
      OBJECTIVE: We developed a computational method (EpiCC) that facilitates pairwise
      comparison of protein sequences based on an immunological property-T-cell epitope
      content-rather than sequence identity, and evaluated its ability to classify
      swine IAV strain relatedness to estimate cross-protective potential of a vaccine
      strain for circulating viruses. METHODS: T-cell epitope relatedness scores were
      assessed for 23 IAV HA sequences representing the major H1 swine IAV phylo
      clusters circulating in North American swine and HA sequences in a commercial
      inactivated vaccine (FluSure XP(r) ). Scores were compared to experimental data
      from previous efficacy studies. RESULTS: Higher EpiCC scores were associated with
      greater protection by the vaccine against strains for 23 field IAV strain vaccine
      comparisons. A threshold for EpiCC relatedness associated with full or partial
      protection in the absence of cross-reactive HI antibodies was identified. EpiCC
      scores for field strains for which FluSure protective efficacy is not yet
      available were also calculated. CONCLUSION: EpiCC thresholds can be evaluated for
      predictive accuracy of protection in future efficacy studies. EpiCC may also
      complement HI cross-reactivity and phylogeny for selection of influenza strains
      in vaccine development.

PMID- 29054119
TI  - Pollinator-independent orchid attracts biotic pollinators due the production of
      lipoidal substances.
AB  - Flowering plants often depend on the attraction of biotic pollinators for sexual
      reproduction. Consequently, the emergence and maintenance of selected floral
      attributes related to pollinator attraction and rewarding are driven by
      pollinator pressure. In this paper we explore the effect of pollinators,
      rainfall, temperature and air humidity on the reproduction of a Brazilian
      terrestrial orchid, Cranichis candida based on data of phenology, flower
      resources, olfactory and visual attraction cues, pollinators and breeding system.
      The flowers of C. candida are strongly protandrous and pollinated by workers of
      the social native bee Tetragonisca angustula. The bees collect labellar lipoidal
      substances (wax scales), which are transported to the nest. The lipoidal
      substance is composed of sterols, hydrocarbons and terpenes. The last presumably
      protects the bees and their nests against pathogens and other arthropods. C.
      candida sets fruits through biotic self- and cross-pollination, and spontaneously
      due the action of raindrops on flowers. Our results indicate that in C. candida,
      although rain-mediated spontaneous self-pollination happens, fructification
      mediated by biotic pollinations also occurs, which may result in fruit set by
      cross-pollination. A mixed pollination system must result in higher genetic
      variability when compared to species whose fruits are produced entirely by self
      pollination. On the other hand, autogamy is a form of reproductive assurance, and
      has commonly evolved where pollination services are rare or absent.

PMID- 29054121
TI  - Multisensory modulation of experimentally evoked perceptual distortion of the
      face.
AB  - BACKGROUND: Chronic oro-facial pain patients often perceive the painful face area
      as "swollen" without clinical signs, that is a perceptual distortion (PD). Local
      anaesthetic (LA) injections in healthy participants are also associated with PD.
      OBJECTIVE: The aim was to explore whether PD evoked by LA into the infraorbital
      region could be modulated by adding mechanical stimulation (MS) to the affected
      area. METHODS: Mechanical stimulation was given with a brush and a 128-mN von
      Frey filament. Firstly, sixty healthy participants were randomly divided into
      three groups: (i) LA control, (ii) LA with MS, (iii) isotonic solution (ISO) with
      MS as an additional control condition. To further examine the role of a
      multisensory modulation, an additional experiment was conducted. Twenty
      participants received LA with MS (filament) in addition to visual feedback of
      their distorted face. The results of the two experiments are presented together.
      RESULTS: All three LA groups experienced PD; per contra, PD was not reported in
      the ISO group. MS alone did not change the magnitude of PD: brush (P = .089),
      filament (P = .203). However, when the filament stimulation was combined with
      additional visual information of a distorted face, there was observable decrease
      in PD (P = .002). CONCLUSION: The findings indicate the importance of
      multisensory integration for PD and represent a significant step forward in the
      understanding of the factors that may influence this common condition. Future
      studies are encouraged to investigate further the cortical processing for
      possible implications for PD in pain management.

PMID- 29054123
TI  - Good publication practice in physiology 2017: Current Revisions of the
      Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly
      Work in Medical Journals.

PMID- 29054122
TI  - Assessing the reporting quality of influenza outbreaks in the community.
AB  - BACKGROUND: High-quality reporting of outbreak characteristics is fundamental to
      understand the behaviour of various strains of influenza virus and the impact of
      outbreak management strategies. However, few studies have systematically
      evaluated the quality of outbreak reporting. OBJECTIVES: To conduct a systematic
      analysis and assessment for reporting quality of influenza outbreaks based on a
      modified version of the STROBE statement, and to examine characteristics
      associated with reporting quality. METHODS: A literature search was conducted
      across 3 online databases (PubMed, Web of Science, MEDLINE) for reports of
      influenza outbreaks (pandemic H1N1, avian, seasonal). The quality of reports
      meeting our eligibility criteria was assessed using the Modified STROBE criteria
      and assigned a score of 30. Mean differences (MD) and 95% confidence intervals
      (CI) were reported for comparisons of study characteristics. RESULTS: Sixty-four
      outbreak reports were available for analyses. The average Modified STROBE score
      was 20/30. Peer-reviewed articles were associated with a better quality of
      reporting (MD 2.79, 95% CI 0.79-4.78). Likewise, reports from authors affiliated
      with public health agencies were associated with better quality than those from
      academic institutions (MD 1.65, 95% CI-0.27-3.56). CONCLUSIONS: The development
      of explicit reporting guidelines specifically geared towards reporting of
      outbreak investigations proved to be useful. Providing information on patient
      characteristics, investigation details in introduction and results, as well as
      addressing limitations that could have biased the findings, were frequently
      missing in the published reports.

PMID- 29054124
TI  - Historical demography and colonization pathways of the widespread intertidal
      seaweed Hormosira banksii (Phaeophyceae) in southeastern Australia.
AB  - The palaeoceanography of southern Australia has been characterized by fluctuating
      sea levels during glacial periods, changing temperature regimes and modified
      boundary currents. Previous studies on genetic structuring of species in
      southeastern Australia have focused mainly on the differentiation of eastern and
      western populations while the potential role of Bass Strait as a region of
      overlap for three biogeographic provinces (Peronia, Maugea, and Flindersia) has
      been largely ignored. This study aimed to explore the likely roles of historic
      and contemporary factors in determining divergence patterns in the habitat
      forming intertidal seaweed Hormosira banksii in southeastern Australia with a
      special focus on postglacial dispersal into Bass Strait. We examined the genetic
      diversity of 475 Hormosira specimens collected from 19 sites around southern
      Australia using DNA sequence analysis of cytochrome oxidase 1. Three major
      haplotype groups were identified (western, centre and eastern) corresponding with
      the three existing biogeographical provinces in this region. Historic break
      points appeared to be retained and reinforced by modern day dispersal barriers.
      Phylogeographic grouping of Hormosira reflected a combination of historic and
      contemporary oceanography. As western and eastern group haplotypes were largely
      absent within Bass Strait, re-colonization after the last glacial maximum
      appeared to have originated from refuges within or near present day Bass Strait.
      Patterns of genetic structure for Hormosira are consistent with other marine
      species in this region and highlight the importance of biogeographical barriers
      in contributing to modern genetic structure.

PMID- 29054125
TI  - External validation of a cancer risk prediction model for suspected head and neck
      cancer referrals.

PMID- 29054126
TI  - A review of periorbital cellulitis guidelines in Fifty-One Acute Admitting Units
      in the United Kingdom.

PMID- 29054127
TI  - Reducing the Prevalence of Smoking: Policy Measures and Focusing on Specific
      Populations.

PMID- 29054128
TI  - Combination Varenicline/Bupropion Treatment Benefits Highly Dependent Smokers in
      an Adaptive Smoking Cessation Paradigm.
AB  - Introduction: This study replicated and extended results of a previous trial,
      which found that combination varenicline/bupropion treatment increased smoking
      abstinence in smokers who were male, highly dependent, and who did not respond to
      prequit nicotine patch treatment with a >50% reduction in expired-air carbon
      monoxide in the first week. Methods: One hundred and twenty-two male nicotine
      patch nonresponders and 52 responders were identified. Smokers in each group were
      randomized to receive 12 weeks of varenicline plus bupropion treatment versus
      varenicline plus placebo. The primary outcome was continuous smoking abstinence
      at weeks 8-11 after the target quit date. Results: For smokers with a high level
      of dependence, judged by having a baseline Fagerstrom Test for Nicotine
      Dependence (FTND) score >= 6 and cigarette consumption >= 20/d, combination
      varenicline/bupropion treatment increased the abstinence rate relative to
      varenicline alone: 71.0% versus 43.8% (odds ratio = 3.14; 95% confidence interval
      = 1.11-8.92, p [one tailed] = .016). In contrast, less dependent smokers did not
      show a benefit of combination treatment relative to varenicline (abstinence rates
      of 32.1% vs. 45.6%, respectively); there was a significant interaction of
      treatment and dependence level. Patch nonresponders tended to benefit the most
      from combination treatment, which was well tolerated overall. Conclusions:
      Combination varenicline/bupropion treatment proved significantly more efficacious
      than varenicline alone among highly dependent male smokers. These results,
      together with prior studies, support an adaptive treatment paradigm that assigns
      smoking cessation treatment according to baseline smoker characteristics and
      initial response to nicotine patch treatment. Implications: This study
      replicated, in a prospective manner, an important and surprising retrospective
      finding from a previous clinical trial, which showed that a specific
      subpopulation of smokers benefited substantially from receiving a combination
      treatment of varenicline plus bupropion, relative to varenicline plus placebo.
      Specifically, male smokers having high baseline nicotine dependence (FTND score
      >= 6 and cigarette consumption >= 20/d), showed a marked increase in smoking
      abstinence rate on combination pharmacotherapy. The present study likewise found
      an enhancement in end-of-treatment abstinence rate in this subgroup, from 43.8%
      to 71.0%. The adaptive treatment paradigm, which classifies smokers based on
      initial dependence level and response to prequit nicotine patch treatment, may be
      used to identify target populations of smokers whose success can be enhanced by
      intervening with combination pharmacotherapy before the quit-smoking date. Trial
      Registration: ClinicalTrials.gov identifier: NCT01806779.

PMID- 29054129
TI  - BioPlex Display: An Interactive Suite for Large-Scale AP-MS Protein-Protein
      Interaction Data.
AB  - The development of large-scale data sets requires a new means to display and
      disseminate research studies to large audiences. Knowledge of protein-protein
      interaction (PPI) networks has become a principle interest of many groups within
      the field of proteomics. At the confluence of technologies, such as cross-linking
      mass spectrometry, yeast two-hybrid, protein cofractionation, and affinity
      purification mass spectrometry (AP-MS), detection of PPIs can uncover novel
      biological inferences at a high-throughput. Thus new platforms to provide
      community access to large data sets are necessary. To this end, we have developed
      a web application that enables exploration and dissemination of the growing
      BioPlex interaction network. BioPlex is a large-scale interactome data set based
      on AP-MS of baits from the human ORFeome. The latest BioPlex data set release
      (BioPlex 2.0) contains 56 553 interactions from 5891 AP-MS experiments. To
      improve community access to this vast compendium of interactions, we developed
      BioPlex Display, which integrates individual protein querying, access to
      empirical data, and on-the-fly annotation of networks within an easy-to-use and
      mobile web application. BioPlex Display enables rapid acquisition of data from
      BioPlex and development of hypotheses based on protein interactions.

PMID- 29054131
TI  - Detection of Hydrogen Peroxide with Fluorescent Dyes.
AB  - SIGNIFICANCE: Hydrogen peroxide (H2O2) is a powerful effector of redox signaling.
      It is able to oxidize cysteine residues, metal ion centers, and lipids.
      Understanding H2O2-mediated signaling requires, to some extent, measurement of
      H2O2 level. Recent Advances: Chemically and genetically encoded fluorescent
      probes for the detection of H2O2 are currently the most sensitive and popular.
      Novel probes are constantly being developed, with the latest progress particular
      with boronates and genetically encoded probes. CRITICAL ISSUES: All currently
      available probes display limitations in terms of sensitivity, local and temporal
      resolution, and specificity in the detection of low H2O2 concentrations. In this
      review, we discuss the power of fluorescent probes and the systems in which they
      have been successfully employed. Moreover, we recommend approaches for overcoming
      probe limitations and for the avoidance of artifacts. FUTURE DIRECTIONS: Constant
      improvements will lead to the generation of probes that are not only more
      sensitive but also specifically tailored to individual cellular compartments.
      Antioxid. Redox Signal. 29, 585-602.

PMID- 29054130
TI  - Reaction Coordinate Leading to H2 Production in [FeFe]-Hydrogenase Identified by
      Nuclear Resonance Vibrational Spectroscopy and Density Functional Theory.
AB  - [FeFe]-hydrogenases are metalloenzymes that reversibly reduce protons to
      molecular hydrogen at exceptionally high rates. We have characterized the
      catalytically competent hydride state (Hhyd) in the [FeFe]-hydrogenases from both
      Chlamydomonas reinhardtii and Desulfovibrio desulfuricans using 57Fe nuclear
      resonance vibrational spectroscopy (NRVS) and density functional theory (DFT).
      H/D exchange identified two Fe-H bending modes originating from the binuclear
      iron cofactor. DFT calculations show that these spectral features result from an
      iron-bound terminal hydride, and the Fe-H vibrational frequencies being highly
      dependent on interactions between the amine base of the catalytic cofactor with
      both hydride and the conserved cysteine terminating the proton transfer chain to
      the active site. The results indicate that Hhyd is the catalytic state one step
      prior to H2 formation. The observed vibrational spectrum, therefore, provides
      mechanistic insight into the reaction coordinate for H2 bond formation by [FeFe]
      hydrogenases.

PMID- 29054132
TI  - Measuring mental workload: ocular astigmatism aberration as a novel objective
      index.
AB  - This study assessed the effect of two perceptually matched mental tasks with
      different levels of mental demand on ocular aberrations in a group of young
      adults. We measured ocular aberration with a wavefront sensor, and total,
      internal and corneal RMS (root mean square) aberrations were calculated from
      Zernike coefficients, considering natural and scaled pupils (5, 4.5, and 4 mm).
      We found that total, internal and corneal astigmatism RMS showed significant
      differences between mental tasks with natural pupils (p < .05), and this effect
      was maintained with 5 mm scaled pupils (total RMS astigmatism, p < .05).
      Consistently, pupil size, intraocular pressure, perceived mental load and
      cognitive performance were influenced by the level of mental complexity (p < .05
      for all). The findings suggest that ocular astigmatism aberration, mediated by
      intraocular pressure, could be an objective, valid reliable index to evaluate the
      impact of cognitive processing in conjunction with others physiological markers
      in real world contexts. Practitioner Summary: The search continues for a valid,
      reliable, convenient method of measuring mental workload. In this study we found
      ocular astigmatism aberration is sensitive to the cumulative effect of mental
      effort. It shows promise of being a novel ocular index which may help to assess
      mental workload in real situations.

PMID- 29054133
TI  - Effects of Intrathecal Injection of the Conditioned Medium from Bone Marrow
      Stromal Cells on Spinal Cord Injury in Rats.
AB  - Bone marrow stromal cells (BMSCs) have been studied for the treatment of spinal
      cord injury (SCI). In previous studies, we showed that the transplantation of
      BMSCs, even though they disappeared from the host spinal cord within 1-3 weeks
      after transplantation, improved locomotor behaviors and promoted axonal
      regeneration. This result led to the hypothesis that BMSCs might release some
      neurotrophic factors effective for the treatment of SCI. The present study
      examined this by injecting the conditioned medium (CM) of BMSCs to treat SCI in
      rats. The spinal cord was contusion-injured, followed immediately by continuous
      injection for 2 weeks of the CM of BMSCs through the cerebrospinal fluid via the
      4th ventricle using an Alzet osmotic pump. Locomotor behaviors evaluated by the
      Basso-Beattie-Bresnahan score were markedly improved in the CM-injection group,
      compared with the control group, at 1 to 4 weeks post-injection. The contusion
      injured site of the spinal cord was identified as an astrocyte-devoid area, which
      contained no astrocytes but was filled with collagen matrices and empty cavities
      of various sizes. Collagen matrices contained type I collagen and laminin.
      Numerous axons extended through the collagen matrices of the astrocyte-devoid
      area. Axons were surrounded by Schwann cells, exhibiting the same morphological
      characteristics as peripheral nerve fibers. The density of axons extending
      through the astrocyte-devoid area was higher in the CM-injection group, compared
      with the control group. CM injection had beneficial effects on locomotor
      improvements and tissue repair, including axonal regeneration, meaning that the
      BMSC-CM stimulated the intrinsic ability of the spinal cord to regenerate.
      Activation of the intrinsic ability of the spinal cord to regenerate by the
      injection of neurotrophic factors such as BMSC-CM is considered to be a safe and
      preferable method for the clinical treatment of SCI.

PMID- 29054134
TI  - Thymus-Derived Mesenchymal Stem Cells for Tissue Engineering Clinical-Grade
      Cardiovascular Grafts.
AB  - Mesenchymal stem cells (MSCs) are attractive tools for regenerative medicine
      because of their multidifferentiation potential and immunomodulation capacity. In
      congenital heart defect surgical correction, replacement grafts lacking growth
      potential are commonly used. Tissue engineering promises to overcome the
      limitations of these grafts. In this study, we hypothesized that human thymus
      derived MSCs are a suitable tool to tissue engineer a living vascular graft with
      good integration and patency once implanted in vivo. Human thymus-derived MSCs
      (hT-MSCs) were identified by the expression of MSC markers and mesenchymal
      differentiation potential. When cultured onto natural scaffold to produce tissue
      engineered graft, hT-MSCs exhibited great proliferation potential and the ability
      to secrete their own extracellular matrix. In addition, when implanted in vivo in
      a piglet model of left pulmonary grafting, the engineered graft exhibited good
      integration within the host tissue, indicating potential suitability for
      corrective cardiovascular surgery. The optimized xeno-free, good manufacturing
      practices-compliant culture system proved to be optimum for large-scale expansion
      of hT-MSCs and production of tissue-engineered cardiovascular grafts, without
      compromising the quality of cells. This study demonstrated the feasibility of
      engineering clinical-grade living autologous replacement grafts using hT-MSCs and
      proved the compatibility of these grafts for in vivo implantation in a left
      pulmonary artery position.

PMID- 29054135
TI  - Alterations in the Timing of Huperzine A Cerebral Pharmacodynamics in the Acute
      Traumatic Brain Injury Setting.
AB  - Traumatic brain injury (TBI) may affect the pharmacodynamics of centrally acting
      drugs. Paired-pulse transcranial magnetic stimulation (ppTMS) is a safe and
      noninvasive measure of cortical gamma-aminobutyric acid (GABA)-mediated cortical
      inhibition. Huperzine A (HupA) is a naturally occurring acetylcholinesterase
      inhibitor with newly discovered potent GABA-mediated antiepileptic capacity,
      which is reliably detected by ppTMS. To test whether TBI alters cerebral HupA
      pharmacodynamics, we exposed rats to fluid percussion injury (FPI) and tested
      whether ppTMS metrics of cortical inhibition differ in magnitude and temporal
      pattern in injured rats. Anesthetized adult rats were exposed to FPI or sham
      injury. Ninety minutes post-TBI, rats were injected with HupA or saline (0.6
      mg/kg, intraperitoneally). TBI resulted in reduced cortical inhibition 90 min
      after the injury (N = 18) compared to sham (N = 13) controls (p = 0.03). HupA
      enhanced cortical inhibition after both sham injury (N = 6; p = 0.002) and TBI (N
      = 6; p = 0.02). The median time to maximum HupA inhibition in sham and TBI groups
      were 46.4 and 76.5 min, respectively (p = 0.03). This was consistent with a
      quadratic trend comparison that projects HupA-mediated cortical inhibition to
      last longer in injured rats (p = 0.007). We show that 1) cortical GABA-mediated
      inhibition, as measured by ppTMS, decreases acutely post-TBI, 2) HupA restores
      lost post-TBI GABA-mediated inhibition, and 3) HupA-mediated enhancement of
      cortical inhibition is delayed post-TBI. The plausible reasons of the latter
      include 1) low HupA volume of distribution rendering HupA confined in the
      intravascular compartment, therefore vulnerable to reduced post-TBI cerebral
      perfusion, and 2) GABAR dysfunction and increased AChE activity post-TBI.

PMID- 29054136
TI  - Combined Methylome and Transcriptome Analysis During Rat Hepatic Stellate Cell
      Activation.
AB  - Hepatic stellate cells (HSCs) are mesenchymal stem cells (MSCs) of the liver.
      They are unique among MSCs, since HSCs remain in a quiescent, retinoid-storing
      state in the normal liver but become activated after liver injury and contribute
      to tissue repair. The epigenetic mechanisms accompanying the transition of HSCs
      from a quiescent to an activated state are in the focus of the present study. We
      investigated the methylome and transcriptome during this process and observed
      profound changes. While the promoter methylation correlated negatively with gene
      expression, the gene-body methylation revealed no clear correlation. Most genes
      with altered expression were associated with cell differentiation. Among them,
      Wilms tumor 1 (Wt1) and Deltex4 (Dtx4) genes were identified as epigenetically
      regulated. Since HSCs were reported to derive from multipotent Wt1-positive cells
      and many differentially expressed genes were associated with cell differentiation
      during their activation, epigenetic alterations are presumably required to enable
      HSC development.

PMID- 29054137
TI  - Interleukin-35 Gene-Modified Mesenchymal Stem Cells Protect Concanavalin A
      Induced Fulminant Hepatitis by Decreasing the Interferon Gamma Level.
AB  - Interleukin 35 (IL-35) is a relatively newly identified cytokine required for the
      regulatory and suppressive functions of regulatory T cells (Treg), playing an
      important role in the prevention of autoimmune diseases. This study used
      mesenchymal stem cells (MSCs) as the gene-delivery vehicles for IL-35 gene
      therapy and investigated their protective effects in Concanavalin A (Con A)
      induced autoimmune hepatitis. Results showed that IL-35 gene modified MSCs (IL-35
      MSCs) can specifically migrate to the injured liver tissues and significantly
      narrow the necrosis areas of injured livers. IL-35-MSCs prevented hepatocyte
      apoptosis by reducing the FASL expression by mononuclear cells. Although MSC
      treatment can alleviate liver injury to some extent, IL-35-MSCs showed a stronger
      protective effect, which means some novel mechanisms exist. The results show that
      IL-35-MSCs could decrease the level of interferon gamma secreted by liver
      mononuclear cells through the JAK1-STAT1/STAT4 signal pathway. In summary, this
      study thus demonstrates a novel and efficient treatment for Con A-induced
      fulminant hepatitis through negatively regulating the secretion of interferon
      gamma, thus providing a novel therapeutic approach for this devastating liver
      disease.

PMID- 29054138
TI  - Mdivi-1 Protects Human W8B2+ Cardiac Stem Cells from Oxidative Stress and
      Simulated Ischemia-Reperfusion Injury.
AB  - Cardiac stem cell (CSC) therapy is a promising approach to treat ischemic heart
      disease. However, the poor survival of transplanted stem cells in the ischemic
      myocardium has been a major impediment in achieving an effective cell-based
      therapy against myocardial infarction. Inhibiting mitochondrial fission has been
      shown to promote survival of several cell types. However, the role of
      mitochondrial morphology in survival of human CSC remains unknown. In this study,
      we investigated whether mitochondrial division inhibitor-1 (Mdivi-1), an
      inhibitor of mitochondrial fission protein dynamin-related protein-1 (Drp1), can
      improve survival of a novel population of human W8B2+ CSCs in hydrogen peroxide
      (H2O2)-induced oxidative stress and simulated ischemia-reperfusion injury models.
      Mdivi-1 significantly reduced H2O2-induced cell death in a dose-dependent manner.
      This cytoprotective effect was accompanied by an increased proportion of cells
      with tubular mitochondria, but independent of mitochondrial membrane potential
      recovery and reduction of mitochondrial superoxide production. In simulated
      ischemia-reperfusion injury model, Mdivi-1 given as a pretreatment or throughout
      ischemia-reperfusion injury significantly reduced cell death. However, the
      cytoprotective effect of Mdivi-1 was not observed when given at reperfusion.
      Moreover, the cytoprotective effect of Mdivi-1 in the simulated ischemia
      reperfusion injury model was not accompanied by changes in mitochondrial
      morphology, mitochondrial membrane potential, or mitochondrial reactive oxygen
      species production. Mdivi-1 also did not affect mitochondrial bioenergetics of
      intact W8B2+ CSCs. Taken together, these experiments demonstrated that Mdivi-1
      treatment of human W8B2+ CSCs enhances their survival and can be employed to
      improve therapeutic efficacy of CSCs for ischemic heart disease.

PMID- 29054139
TI  - MC-Media Pad ACplusTM for Enumeration of Aerobic Counts in a Variety of Foods.
AB  - The MC-Media Pad ACplusTM is a dry, rehydratable film medium for the enumeration
      of aerobic bacterial colonies. The performance of the method in a variety of
      foods was compared to that of U.S. reference methods: U.S. Department of
      Agriculture (USDA) Food Safety and Inspection Service (FSIS) Microbiology
      Laboratory Guidebook (MLG) Chapter 3.02 "Quantitative Analysis of Bacteria in
      Foods as Sanitary Indicators" (USDA/FSIS MLG 3.02); Standard Methods for the
      Examination of Dairy Products (SMEDP) Chapter 6 "Microbiological Count Methods,
      Standard Plate Count Method" (SMEDP 6); AOAC Official MethodSM 966.23
      Microbiological Methods; and ISO 4833-1:2013 "Microbiology of the food chain
      Horizontal method for the enumeration of microorganisms-Part 1: Colony count at
      30 degrees C by the pour plate technique." The validated matrixes included raw
      chicken breast and raw ground pork for USDA/FSIS MLG 3.02; cream cheese and
      yogurt drink for SMEDP 6; parsley, vegetable juice, prawns, tuna pate,
      sandwiches, and pasta salad for AOAC Method 966.23, and raw chicken breast, raw
      ground pork, cream cheese, yogurt drink, parsley, vegetable juice, prawns, tuna
      pate, sandwiches, and pasta salad for ISO 4833-1:2013. In each matrix study, five
      replicates at each of three contamination levels were tested as paired test
      portions. All 10 matrixes were compared to the appropriate U.S. reference methods
      under MC-Media Pad ACplus standard-usage conditions (35 +/- 1 degrees C for 48 +/
      2 h). Across all matrixes, the difference of mean log10 values ranged from -0.43
      to 0.44, within the acceptable range of -0.50 to 0.50. The candidate method
      repeatability SD (sr) varied from 0.03 to 0.23 log10 CFU/g, comparing favorably
      to the reference method SD, which ranged from 0.06 to 0.30 log10 CFU/g. Seven
      matrixes were compared to the appropriate U.S. reference methods under MC-Media
      Pad ACplus rapid-usage conditions (35 +/- 1 degrees C for 24 +/- 2 h). Of the 21
      matrix/concentration combinations, only three instances of difference of mean
      >0.5 log were observed. The ranges of sr values of the rapid-usage candidate
      method (0.023-0.324) and the reference method (0.013-0.236) were similar for the
      seven matrixes tested. All 10 matrixes were compared to the International
      Organization for Standardization (ISO) reference method under MC-Media Pad ACplus
      alternate-method conditions (30 +/- 1 degrees C for 72 +/- 3 h). All 10 matrixes
      yielded a mean difference between methods of <0.5 log, and the ranges of sr
      values were similar between the candidate alternate method (0.037-0.378) and the
      ISO reference method (0.037-0.437). The product consistency study demonstrated no
      significant difference between lots of product and supported the 2-year shelf
      life. Robustness testing yielded no significant differences when small variations
      were made in sample volume, incubation temperature, and incubation time. Thus,
      the data show equivalent or better performance of the MC-Media Pad ACplus method
      compared to the relevant reference methods in support of AOAC Performance Tested
      MethodSM certification.

PMID- 29054141
TI  - Quantitative Detection of Horse Contamination in Cooked Meat Products by ELISA.
AB  - Concerns about the contamination of meat products with horse meat and new
      regulations for the declaration of meat adulterants have highlighted the need for
      a rapid test to detect horse meat adulteration. To address this need,
      Microbiologique, Inc., has developed a sandwich ELISA that can quantify the
      presence of horse meat down to 0.1% (w/w) in cooked pork, beef, chicken, goat,
      and lamb meats. This horse meat authentication ELISA has an analytical
      sensitivity of 0.000030 and 0.000046% (w/v) for cooked and autoclaved horse meat,
      respectively, and an analytical range of quantitation of 0.05-0.8% (w/v) in the
      absence of other meats. The assay is rapid and can be completed in 1 h and 10
      min. Moreover, the assay is specific for cooked horse meat and does not
      demonstrate any cross-reactivity with xenogeneic cooked meat sources.

PMID- 29054142
TI  - Elemental hair analysis: A review of procedures and applications.
AB  - Although exogenous contamination and unreliable reference values have limited the
      utility of scalp hair as a biomarker of chemical elements exposure, its use in
      toxicological, clinical, environmental and forensic investigations is growing and
      becoming more extensive. Therefore, hair elemental analysis is reviewed in the
      current manuscript which spans articles published in the last 10 years. It starts
      with a general discussion of history, morphology and possible techniques for
      elemental analysis, where inductively coupled plasma-mass spectrometry (ICP-MS)
      is clearly highlighted since this technique is leading quantitative ultra-trace
      elemental analysis. Emphasis over sampling, quality assurance, washing procedures
      and sample decomposition is given with detailed protocols compiled in tables as
      well as the utility of hair to identify human gender, age, diseases, healthy
      conditions, nutrition status and contamination sites. Isotope ratio information,
      chemical speciation analysis and analyte preconcentration are also considered for
      hair. Finally, the potential of laser ablation ICP-MS (LA-ICP-MS) to provide
      spatial resolution and time-track the monitoring of elements in hair strands
      instead of conventional bulk analysis is spotlighted as a real future trend in
      the field.

PMID- 29054140
TI  - Acetaminophen Toxicity: Novel Insights Into Mechanisms and Future Perspectives.
AB  - Acetaminophen (APAP) overdose is the most common cause of acute liver failure in
      the US, and decades of intense study of its pathogenesis resulted in the
      development of the antidote N-acetylcysteine, which facilitates scavenging of the
      reactive metabolite and is the only treatment in clinical use. However, the
      narrow therapeutic window of this intervention necessitates a better
      understanding of the intricacies of APAP-induced liver injury for the development
      of additional therapeutic approaches that can benefit late-presenting patients.
      More recent investigations into APAP hepatotoxicity have established the critical
      role of mitochondrial dysfunction in mediating liver injury as well as clarified
      mechanisms of APAP-induced hepatocyte cell death. Thus, it is now established
      that mitochondrial oxidative and nitrosative stress is a key mechanistic feature
      involved in downstream signaling after APAP overdose. The identification of
      specific mediators of necrotic cell death further establishes the regulated
      nature of APAP-induced hepatocyte cell death. In addition, the discovery of the
      role of mitochondrial dynamics and autophagy in APAP-induced liver injury
      provides additional insight into the elaborate cell signaling mechanisms involved
      in the pathogenesis of this important clinical problem. In spite of these new
      insights into the mechanisms of liver injury, significant controversy still
      exists on the role of innate immunity in APAP-induced hepatotoxicity.

PMID- 29054143
TI  - Dual-signal model array sensor based on GQDs/AuNPs system for sensitive protein
      discrimination.
AB  - The accurate differentiation and identification of proteins play a vital role in
      many areas. Herein a novel array sensor is developed for sensitive discrimination
      of proteins, based on the various optical responses of GQDs/AuNPs system towards
      different protein species. The simultaneously generated distinct variations of
      fluorescence and absorbance of GQDs/AuNPs system resulted from the interactions
      between protein species and sensing units contribute to a dual-signal strategy
      for protein discrimination. The protein concentration for complete discrimination
      is low down to 50 nM, and accurate discriminations of protein mixture of
      different concentrations/molar ratio are achieved. The complementary fluorescence
      and absorbance response makes this dual-signal model array sensor practicable to
      sample of complicated matrices, demonstrated by the accurate discrimination of
      protein species in human urine. Moreover, six strains of microorganisms
      originated from three different species are also successfully discriminated with
      100% accuracy (OD600 = 1.0).

PMID- 29054145
TI  - Simple, high efficiency detection of microcystins and nodularin-R in water by
      fluorescence polarization immunoassay.
AB  - This manuscript describes the development of a sensitive, fast and easily
      performed fluorescence polarization immunoassay (FPIA) for detection of
      microcystins (MCs) and nodularin-R (NOD) in water. MCs and NOD, the most
      widespread cyanobacterial toxin are hepatotoxins and tumor promoters, and their
      acute exposure may result in severe health problems in animals and humans. The
      fluorescein-based tracers were synthesized, and for the first time preparative
      high performance liquid chromatography (HPLC) was employed for their
      purification. Optimal tracers for the analysis were selected by evaluating the
      immunochemical activity. Under the optimal conditions, the achieved limits of
      detection (LODs) for MC-LR and NOD were 0.86 and 0.95 MUg L-1, respectively,
      providing a sufficient sensitivity to meet the provisional guideline value
      recommended by the World Health Organization (WHO). An ultra-performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed to
      confirm the accuracy and precision of the FPIA, and no obvious difference in
      recovery between these two methods was found. The correlation coefficients (R2)
      were higher than 0.968. The developed FPIA was easy-to-operate and could be
      completed within 10 min after simple filtration and adjustment of pH for water
      samples. The method can be easily extended for screening of other cyanotoxins,
      representing a versatile strategy for environmental sample analysis.

PMID- 29054144
TI  - Sandwich NP-based biobarcode assay for quantification C-reactive protein in
      plasma samples.
AB  - A NP-based biobarcode for C-reactive protein (CRP) quantification in plasma
      samples is reported for the first time. The assay uses capture antibody
      functionalized magnetic beads (pAbCRP2-MP), multifunctional oligonucleotide
      encoded probes modified with a detection antibody (pAbCRP1-ePSP), and a
      fluorescent DNA microarray. Thus, magnetic beads are added to the sample to form
      immunocomplexes that will be isolated, to then add the codified particles to form
      a sandwich complex with both particles and the target protein, subsequently the
      complexes are treated to release the oligonucleotide codes, which are finally
      hybridized in a fluorescent DNA microarray. The assay has been implemented to the
      analysis of plasma samples being able to quantify this biomarker within 900 ng mL
      1 to 12500 ng mL-1 with an excellent accuracy (mean of recovery of 99.5 +/- 4.2%,
      N = 3). The CRP biobarcode has been used on a small pilot clinical study in which
      plasma samples from patients suffering different pathologies, most of them
      related to cardiovascular diseases (CVDs). The samples have been analyzed and the
      results compared to a reference method demonstrating that the assay can be useful
      for monitoring this biomarker on patients being suspicious to be under risk of
      suffering CVDs or other diseases involving inflammatory processes.

PMID- 29054146
TI  - Highly sensitive and rapid colorimetric sensing platform based on water-soluble
      WOx quantum dots with intrinsic peroxidase-like activity.
AB  - This report outlines a rapid and highly sensitive colorimetric sensing platform
      based on a novel water-soluble WOx quantum dots (QDs) as enzymatic mimics. The
      WOx QDs, synthesized by a green hydrothermal method, were proven to possess
      excellent intrinsic peroxidase-like activity. The peroxidase substrate, 2, 2'
      azinobis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) could be
      catalyzed oxidation by WOx QDs quickly in the present of H2O2 to form a green
      color. Due to its excellent properties such as excellent water-solublity, good
      biocompatibility, easy preparation, and high stability, the proposed system
      showed typical Michaelis-Menten kinetics and high affinity for ABTS and H2O2,
      indicating WOx QDs can be used as satisfactory peroxidase mimics. Together with
      the fast detection process, WOx QDs-based colorimetric sensing system provided a
      facile, sensitive, and accurate method for the determination of H2O2 and glucose.
      The real glucose samples in human serum samples were detected with satisfying
      results. The proposed sensing platform not only expands the applications of WOx
      and WOx QDs-based nanocomposites, but also provides an alternative technique for
      biological, biomedical and environmental sample assay.

PMID- 29054147
TI  - Tetrathiafulvalene aids in the atomic spectroscopic determination of total
      mercury.
AB  - The determination of mercury simultaneously with other elements via inductively
      coupled plasma-mass spectrometry (ICP-MS) in airborne particulate matter (PM2.5)
      is still challenging due to the lack of accuracy for the low level mercury
      concentrations as a result of its volatility and tendency to adhere to the walls
      of the sample introduction system. This study investigated the effect of existing
      (gold and methionine) and new (lithium tetrathiafulvalene carboxylate (LiCTTF))
      preservation agents in order to improve the determination of trace mercury in
      PM2.5 samples. Statistical analysis revealed that a concentration of 10 MUg mL-1
      of LiCTTF was sufficient to obtain highly accurate results with t values of
      0.1044-1.1239 which are considerably less than the critical t value of 1.8 and
      apparent recoveries of 85-100%. An evaluation of the method revealed a spiked
      mercury recovery of 91% and a detection limit of 0.05 ng mL-1. The method was
      tested for the determination of trace metals in PM2.5 from atmospheric samples
      and led to the detection of low elemental concentrations in Singapore's
      atmosphere. The mechanism for the interaction of mercury with LiCTTF and
      tetrathiafulvalene (TTF) was studied by conducting in situ electrochemical
      studies. Cyclic voltammetry and square-wave voltammetry analyses of mercury, and
      mercury in presence of LiCTTF and TTF revealed complexation between the metal and
      sulfur-containing compounds.

PMID- 29054148
TI  - Determination of size and mass-and number-based concentration of biogenic SeNPs
      synthesized by lactic acid bacteria by using a multimethod approach.
AB  - Selenium nanoparticles (SeNPs) were synthesized by a green technology using
      lactic acid bacteria (LAB, Lactobacillus acidophilus, L. delbrueckii subsp.
      bulgaricus and L. reuteri). The exposure of aqueous sodium selenite to LAB led to
      the synthesis of SeNPs. Characterization of SeNPs by transmission electron
      microscopy with energy dispersive X-ray spectrum (EDXS) analysis revealed the
      presence of stable, predominantly monodispersed and spherical SeNPs of an average
      size of 146 +/- 71 nm. Additionally, SeNPs hydrodynamic size was determined by
      dispersive light scattering (DLS) and nanoparticle tracking analysis (NTA). For
      this purpose, a methodology based on the use of surfactants in basic medium was
      developed for isolating SeNPs from the bacterial pellet. The hydrodynamic size
      values provided by DLS and NTA were 258 +/- 4 and 187 +/- 56 nm, respectively.
      NTA measurements of number-based concentration reported values of (4.67+/
      0.30)x109 SeNPs mL-1 with a relative standard deviation lower than 5% (n = 3).
      The quantitative results obtained by NTA were supported by theoretical
      calculations. Asymmetrical flow field flow fractionation (AF4) on line coupled to
      the inductively couple plasma mass spectrometry (ICP-MS) and off-line coupled to
      DLS was further employed to characterize biogenic SeNPs. The distribution of the
      particle size for the Se-containing peak provide an average size of (247 +/- 14)
      nm. The data obtained by independent techniques were in good agreement and the
      developed methodology could be implemented for characterizing NPs in complex
      matrices such as biogenic nanoparticles embedded inside microbial material.

PMID- 29054149
TI  - Application of a trap-free two-dimensional liquid chromatography combined with
      ion trap/time-of-flight mass spectrometry for separation and characterization of
      impurities and isomers in cefpiramide.
AB  - High-resolution mass spectrometry had been routinely used for structure
      identification of impurity. However, all LC-MS methods were based on a volatile
      mobile phase, and a non-volatile system is used in the official analytical method
      of United States Pharmacopoeia for cefpiramide which limited the use of mass
      spectrometry for structure characterization of the impurities. Here we presented
      the utilization of a trap-free two-dimensional liquid chromatography coupled to
      high resolution ion trap/time-of-flight mass spectrometry (2D LC-IT-TOF MS) with
      positive and negative modes of electrospray ionization for characterization of
      eight impurities in cefpiramide. Trap-free two-dimensional liquid chromatography
      and online desalting technique made it possible to characterize the impurity in
      cefpiramide in the condition of official standard, and the TIC chromatogram of LC
      MS was in conformity with the LC chromatogram of the official analytical method
      in the peak sequence of impurities, which could further improve the method of
      official monographs in pharmacopoeias. Each peak separated by the non-volatile
      mobile phase was trapped by a 20 MUL quantitative loop then transferred into a
      system with a volatile mobile phase connected to a MS detector. In the first
      dimension, the column was Kromasil C8 analytical column (250 mm * 4.6 mm, 5 MUm)
      with a non-volatile salt mobile phase at the flow rate of 0.8 mL min-1. In the
      second dimension, the column was Shimadzu Shim-pack GISS C18 (50 mm * 2.1 mm, 1.9
      MUm) with a volatile salt mobile phase at the flow rate of 0.3 mL min-1. Through
      the multiple heart-cutting 2D-LC approach and online desalting technique, the
      problem of incompatibility between non-volatile salt mobile phase and mass
      spectrometry was solved completely. The fragmentation behavior of cefpiramide and
      its eight impurities were studied. The structures of eight impurities in
      cefpiramide drug substance were deduced based on the HPLC-MSn data, in which
      seven impurities were novel impurities. The forming mechanisms of degradation
      products in cefpiramide were also studied.

PMID- 29054150
TI  - Pesticides in essential oils: Occurrence and concentration in organic and
      conventional orange essential oils from eleven geographical origins.
AB  - In this paper is described for the first time the application of both gas
      chromatography-tandem mass spectrometry (GC-MS/MS) and ultra performance liquid
      chromatography-quadrupole-time of flight-mass spectrometry (UPLC-QTOF-MS) to the
      determination of 75 priority pesticides in orange essential oils (EOs). The
      sample preparation consisted in a 10-fold dilution of orange EO followed by a
      direct injection for GC-MS/MS technique and a freeze-out step in the case of UPLC
      QTOF-MS analysis. The analytical methods were validated using the SANCO criteria
      and gave reporting limits (RLs) of 10 MUg L-1, 25 MUg L-1, 50 MUg L-1 and 100 MUg
      L-1 for 57, 13, 4 and 1 pesticides, respectively. The analysis of four others EOs
      in the context of a proficiency test demonstrated very good performance and
      versatility of the methods with a detection rate of 100%, 97.8% of correct
      quantifications and no false negative. Then 49 orange EOs of known origin and
      quality were analysed using the standard addition procedure. It enabled to
      highlight significant matrix effects leading to differences in response factor up
      to 9.0 in GC-MS/MS and 53.1 in UPLC-QTOF-MS, between an orange EO sample to
      another. It was found that a conventional EO contained on average 17 pesticides
      for a total concentration of 5.1 mg L-1. Up to 29 different pesticides, 39 in the
      case of a concentrated EO, were detected in one sample and the sum of the
      concentration reached 51.1 mg L-1. Regarding the organic samples, none were free
      of pesticides but the contamination was found to be clearly lower than in
      conventional EOs. It was found that an organic orange EO contained on average 4
      pesticides for a total concentration of 0.087 mg L-1.

PMID- 29054151
TI  - Enhanced MS/MS coverage for metabolite identification in LC-MS-based untargeted
      metabolomics by target-directed data dependent acquisition with time-staggered
      precursor ion list.
AB  - Metabolite identification is one of the major bottlenecks in liquid
      chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics owing to
      the difficulty of acquiring MS/MS information of most metabolites detected. Data
      dependent acquisition (DDA) has been currently used to acquire MS/MS data in
      untargeted metabolomics. When dealing with the complex biological samples, top-n
      based DDA method selects only a small fraction of the ions for fragmentation,
      leading to low MS/MS coverage of metabolites in untargeted metabolomics. In this
      study, we proposed a novel DDA method to improve the performance of MS/MS
      acquisition in LC-MS-based untargeted metabolomics using target-directed DDA (t
      DDA) with time-staggered precursor ion lists (ts-DDA). Full scan-based untargeted
      analysis was applied to extract the target ions. After peak alignment, ion
      filtration, and ion fusion, the target precursor ion list was generated for
      subsequent t-DDA and ts-DDA. Compared to the conventional DDA, the ts-DDA
      exhibits the better MS/MS coverage of metabolomes in a plasma sample, especially
      for the low abundant metabolites. Even in high co-elution zones, the ts-DDA also
      showed the superiority in acquiring MS/MS information of co-eluting ions, as
      evidenced by better MS/MS coverage and MS/MS efficiency, which was mainly
      attributed to the pre-selection of precursor ion and the reduced number of
      concurrent ions. The newly developed method might provide more informative MS/MS
      data of metabolites, which will be helpful to increase the confidence of
      metabolite identification in untargeted metabolomics.

PMID- 29054152
TI  - Target-initiated labeling for the dual-amplified detection of multiple microRNAs.
AB  - Herein we exploited a novel target-initiated labeling strategy for the multiplex
      detection of microRNAs (miRNAs) by coupling duplex-specific nuclease (DSN) with
      terminal deoxynucleotidyl transferase (TdT). In the presence of target miRNA, the
      immobilized and 3'-blocked capture probes hybridized with target and thus the
      formed DNA-RNA hybrid was recognized by DSN. DSN mediated the digestion of 3'
      phosphated capture probes (CPs) in the hybrids and synchronously target was
      released and recycled for another round of hybridization and cleavage. The
      cleaved CP fragments with a free 3'-OH were then elongated and labeled with
      multiple biotin-dUTP nucleotides by TdT. Fluorescence reporter streptavidin
      phycoerythin was finally added to react with the immobilized biotins and render
      fluorescence signals. This dual-amplification labeling strategy was successfully
      demonstrated to sensitively detect multiple miRNAs, taking advantage of DSN
      mediated target recycling and TdT-catalyzed multiple signal modification with
      analysis by a commercial Luminex xMAP array platform. Our experimental results
      showed the simultaneous quantitative measurement of three sequence-specific
      miRNAs at concentrations from 1 pM to 2.5 nM. Attempts were also made to directly
      detect miRNAs in total RNA extracted from cancer cells. The dual-amplification
      labeling strategy reported here shows a great potential for the development of a
      method for the multiplexed, sensitive, selective, and simple analysis of multiple
      miRNAs in tissues or cells for biomedical research and clinical early diagnosis.

PMID- 29054153
TI  - Colorimetric analysis of lipopolysaccharides based on its self-assembly to
      inhibit ion transport.
AB  - A new strategy is proposed based on inhibition of ion transport by lipid bilayer
      derived from spontaneous assembly of lipopolysaccharides (LPS), thereby a
      colorimetric method is established for analysis of LPS. At acidic pH values, LPS
      can specially bind with aminophenylboronic acid modified assembled magnetic
      nanospheres (APBA/AMNSs), resulting in formation of lipid bilayer around
      APBA/AMNSs. Under acidic condition, the lipid bilayer can inhibit the release of
      iron ions from AMNSs into the solution so as to decrease the oxidized extent of
      2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt mediated
      by hydrogen peroxide. Using the established method, LPS can be detected over the
      wide linear detection range with the low detection limit. With good selectivity,
      reproductivity, and simplicity, the method is accurate in LPS tests of real
      drinking samples.

PMID- 29054154
TI  - Flavonol based surface modification of doped chalcogenide nanoflakes as an
      ultrasensitive fluorescence probe for Al3+ ion.
AB  - A highly selective novel fluorescent probe was prepared by using surface modified
      ZnS:Mn nanoparticles, functionalized with morin, a flavonol. SEM investigations
      of the heterostructures prepared using wet chemical precipitation technique
      revealed a nanoflake type of morphology. HR-TEM and powder XRD analysis confirmed
      the crystalline planes corresponding to Wurtzite ZnS. The functionalized
      nanoparticles were characterized using Raman, XPS and FTIR which confirms the
      binding of morin to the nanoparticles via surface coordination. The prepared
      probe selectively interacts with Al3+ ions which has been used as an
      ultrasensitive analytical tool for determination of Al3+ ions. A major advantage
      of the proposed method is that the other metal ions closely associated with Al3+
      did not interfere with the analysis. The detection limit and the quantitation
      limit were found to be 0.07 nM and 0.20 nM respectively with a linear dynamic
      range 0.20 nM-80 nM. The method was successfully applied to environmental water
      samples and other complex matrices.

PMID- 29054155
TI  - Polymers and coronary stents: have we come full circle?

PMID- 29054157
TI  - Corrigendum to "Antibody neutralization of retargeted measles viruses" [Virology
      454-455 (2014) 237-246].

PMID- 29054156
TI  - Potential of transcatheter aortic valve replacement to improve post-procedure
      renal function.
AB  - BACKGROUND: Baseline comorbidities including renal dysfunction are frequently
      found in patients treated with transcatheter aortic valve replacement (TAVR) and
      may increase the risks of acute kidney injury (AKI), although some of them may
      actually improve renal function. We aimed to evaluate the potential of TAVR to
      acutely improve post-procedure renal function. METHODS: This is a prospective
      single-center registry of consecutive patients with severe symptomatic aortic
      stenosis treated by transfemoral TAVR. Creatinine levels were determined at
      baseline and daily until hospital discharge. AKI was defined according to VARC-2
      criteria. Patients who had improvement of creatinine levels >25% were classified
      as having TAVR induced renal function improvement (TIRFI). RESULTS: A total of 69
      patients undergoing TAVR were included, with a mean age of 83.0+/-7.4 years,
      being 24.6% diabetics, with a median STS score of 9.2 (5.1-21.6). Using the VARC
      2 criteria, the majority of patients (64.6%) did not have renal impairment, while
      AKI was detected in 35.4% of the patients. Importantly, in those with prior
      severe renal dysfunction (clearance <30mL/min/1.73m2) or diabetes, AKI reached up
      to 50% and 56.3% of the patients, respectively. Conversely, acute kidney recovery
      (TIRFI) occurred in 12 patients (18.5%) being >50% in 1 patient (1.5%), and at
      hospital discharge the majority of the patients (88.6%) left the hospital in
      their original or better renal function categories. CONCLUSION: Despite multiple
      comorbidities in a selected TAVR-population and the use of contrast media, TAVR
      did not impair renal function in a majority of patients, with a significant
      proportion of them rather having acute renal function improvement.

PMID- 29054158
TI  - Corrigendum to "Each of the eight simian hemorrhagic fever virus minor structural
      proteins is functionally important" [Virology 462-463 (2014) 351-362].

PMID- 29054159
TI  - Relationship between foramen magnum position and locomotion in extant and extinct
      hominoids.
AB  - From the Miocene Sahelanthropus tchadensis to Pleistocene Homo sapiens, hominins
      are characterized by a derived anterior position of the foramen magnum relative
      to basicranial structures. It has been previously suggested that the anterior
      position of the foramen magnum in hominins is related to bipedal locomotor
      behavior. Yet, the functional relationship between foramen magnum position and
      bipedal locomotion remains unclear. Recent studies, using ratios based on cranial
      linear measurements, have found a link between the anterior position of the
      foramen magnum and bipedalism in several mammalian clades: marsupials, rodents,
      and primates. In the present study, we compute these ratios in a sample including
      a more comprehensive dataset of extant hominoids and fossil hominins. First, we
      verify if the values of ratios can distinguish extant humans from apes. Then, we
      test whether extinct hominins can be distinguished from non-bipedal extant
      hominoids. Finally, we assess if the studied ratios are effective predictors of
      bipedal behavior by testing if they mainly relate to variation in foramen magnum
      position rather than changes in other cranial structures. Our results confirm
      that the ratios discriminate between extant bipeds and non-bipeds. However, the
      only ratio clearly discriminating between fossil hominins and other extant apes
      is that which only includes basicranial structures. We show that a large
      proportion of the interspecific variation in the other ratios relates to changes
      in facial, rather than basicranial, structures. In this context, we advocate the
      use of measurements based only on basicranial structures when assessing the
      relationship between foramen magnum position and bipedalism in future studies.

PMID- 29054160
TI  - 3D geometric morphometrics of thorax variation and allometry in Hominoidea.
AB  - Ever since the seminal papers of Keith and Schultz, hominoid primate ribcages
      have been described as either "funnel-" or "barrel-shaped." Following this
      dichotomic typology, it is currently held that Homo sapiens and hylobatids
      (gibbons and siamangs) share a barrel-shaped ribcage and that they are more
      similar to each other than to the funnel-shaped thoraces of great apes (Gorilla,
      Pan, and Pongo). Other researchers hypothesized that thoracic width and the
      invagination of the thoracic spine into the thorax are related to allometry.
      However, analyses that take into account the complex three-dimensional (3D) shape
      of the ribcage are lacking. Here, we address hypotheses about thorax shape and
      evolution using 3D morphometrics of thoraces in anatomical connection obtained by
      computed tomography scans of 23 hominoid cadavers and 10 humans and examining
      thorax compartments composed of seven ribs (1-7 thorax) and of 11 ribs (1-11
      thorax). In the 1-7 thorax analyses, the human thorax is uniquely flat because of
      torsion of the upper and central ribs, differing from all non-human hominoids
      including hylobatids. In the 1-11 thorax analyses, humans are markedly different
      from African great apes, with hylobatids and orangutans intermediate. In full
      shape space analyses, affinities between orangutans and humans on the one hand
      and between hylobatids and African great apes on the other are evident.
      Therefore, we reject the hypothesis that humans and hylobatids bear any special
      affinities in overall 3D thorax shape to each other. We find that larger thoraces
      are wider and flatter, with a more invaginated spine, supporting the allometric
      hypothesis. Hominoid thorax variation shows complex interactions between
      allometry, rib curves, torsion, and declination, and the morphology of the costo
      vertebral joint and the thoracic vertebral column. When considering functional
      specializations alongside phylogenetic relationships, an overly simplistic
      dichotomy between funnel-shaped and barrel-shaped thoraces is not supported.

PMID- 29054162
TI  - A chronological framework connecting the early Upper Palaeolithic across the
      Central Asian piedmont.
AB  - Central Asia has delivered significant paleoanthropological discoveries in the
      past few years. New genetic data indicate that at least two archaic human species
      met and interbred with anatomically modern humans as they arrived into northern
      Central Asia. However, data are limited: known archaeological sites with lithic
      assemblages generally lack human fossils, and consequently identifying the
      archaeological signatures of different human groups, and the timing of their
      occupation, remains elusive. Reliable chronologic data from sites in the region,
      crucial to our understanding of the timing and duration of interactions between
      different human species, are rare. Here we present chronologies for two open air
      Middle to Upper Palaeolithic (UP) sequences from the Tien Shan piedmont in
      southeast Kazakhstan, Maibulak and Valikhanova, which bridge southern and
      northern Central Asia. The chronologies, based on both quartz optically
      stimulated luminescence (OSL) and polymineral post-infrared infrared luminescence
      (pIR-IRSL) protocols, demonstrate that technological developments at the two
      sites differ substantially over the ~47-19 ka time span. Some of the innovations
      typically associated with the earliest UP in the Altai or other parts of
      northeast Asia are also present in the Tien Shan piedmont. We caution against
      making assumptions about the directionality of spread of these technologies until
      a larger, better defined database of transitional sites in the region is
      available. Connections between the timing of occupation of regions, living area
      setting and paleoenvironmental conditions, while providing hypotheses worth
      exploring, remain inconclusive. We cautiously suggest a trend towards increasing
      occupation of open air sites across the Central Asian piedmont after ~40 ka,
      corresponding to more humid climatic conditions which nevertheless included
      pulses of dust deposition. Human occupation persisted into the Last Glacial
      Maximum, despite cooler, and possibly drier, conditions. Our results thus provide
      additional data to substantiate arguments for occupation of Central Asia.

PMID- 29054163
TI  - New dental and postcranial material of Agerinia smithorum (Primates, Adapiformes)
      from the type locality Casa Retjo-1 (early Eocene, Iberian Peninsula).
AB  - New material attributed to Agerinia smithorum from Casa Retjo-1 (early Eocene, NE
      Iberian Peninsula), consisting of 13 isolated teeth and a fragment of calcaneus,
      is studied in this work. These fossils allow the first description of the
      calcaneus and the upper premolars for the genus Agerinia, as well as the first
      description of the P2 and M2 for A. smithorum. The newly recovered lower teeth
      are virtually identical to the holotype of A. smithorum and are clearly
      distinguishable from the other species of Agerinia. The upper teeth also show
      clear differences with Agerinia marandati. The morphology of the calcaneal
      remains reveals that A. smithorum practiced a moderately active arboreal
      quadrupedal mode of locomotion, showing less leaping proclivity than notharctines
      but more than asiadapids. All the morphological features observed in the
      described material reinforce the hypothesis of a single lineage consisting of the
      species A. smithorum, A. marandati, and Agerinia roselli. Furthermore, the
      phylogenetic analysis developed in this work, which incorporates the newly
      described remains of A. smithorum, maintains the position of Agerinia as closely
      related to sivaladapids and asiadapids.

PMID- 29054164
TI  - A new primate assemblage from La Verrerie de Roches (Middle Eocene, Switzerland).
AB  - Primates reached a great abundance and diversity during the Eocene, favored by
      warm temperatures and by the development of dense forests throughout the Northern
      Hemisphere. Here we describe new primate material from La Verrerie de Roches, a
      Middle Eocene karstic infill situated in the Jura Region (Switzerland),
      consisting of more than 80 dental remains. The primate assemblage from La
      Verrerie de Roches includes five different taxa. The best represented primate is
      Necrolemur aff. anadoni, similar in size and overall morphology to Necrolemur
      anadoni but resembling in some features the younger species Necrolemur antiquus.
      Microchoerines are also represented by two species of Pseudoloris, P. pyrenaicus
      and Pseudoloris parvulus, constituting the unique joint record of these two
      species known up to now. Remains of Adapiformes are limited to one isolated tooth
      of a large anchomomyin and another tooth belonging to the small adapine
      Microadapis cf. sciureus. The studied primate association allows assigning La
      Verrerie de Roches to the Robiacian Land Mammal Age. More specifically, this site
      can be confidently situated between the MP15 and MP16 reference levels, although
      the primate assemblage probably indicates some degree of temporal mixing. This is
      the first record of P. pyrenaicus and a form closely related to N. anadoni out of
      the Iberian Peninsula. The identification of these microchoerines in Switzerland
      gives further support to the connection of NE Spain and Central Europe during the
      Middle Eocene.

PMID- 29054165
TI  - The origin of bipedality as the result of a developmental by-product: The case
      study of the olive baboon (Papio anubis).
AB  - In this paper, we point to the importance of considering infancy in the emergence
      of new locomotor modes during evolution, and particularly when considering
      bipedal walking. Indeed, because infant primates commonly exhibit a more diverse
      posturo-locomotor repertoire than adults, the developmental processes of
      locomotion represent an important source of variation upon which natural
      selection may act. We have had the opportunity to follow the development of
      locomotion in captive individuals of a committed quadrupedal primate, the olive
      baboon (Papio anubis). We observed six infants at two different stages of their
      development. In total, we were able to analyze the temporal parameters of 65
      bipedal steps, as well as their behavioral components. Our results show that
      while the basic temporal aspects of the bipedal walking gait (i.e., duty factor,
      dimensionless frequency, and hind lag) do not change during development, the
      baboon is able to significantly improve the coordination pattern between hind
      limbs. This probably influences the bout duration of spontaneous bipedal walking.
      During the same developmental stage, the interlimb coordination in quadrupedal
      walking is improved and the proportion of quadrupedal behaviors increases
      significantly. Therefore, the quadrupedal pattern of primates does not impede the
      developmental acquisition of bipedal behaviors. This may suggest that the same
      basic mechanism is responsible for controlling bipedal and quadrupedal
      locomotion, i.e., that in non-human primates, the neural networks for quadrupedal
      locomotion are also employed to perform (occasional) bipedal walking. In this
      context, a secondary locomotor mode (e.g., bipedalism) experienced during infancy
      as a by-product of locomotor development may lead to evolutionary novelties when
      under appropriate selective pressures.

PMID- 29054167
TI  - Using principal trabecular orientation to differentiate joint loading orientation
      in the 3rd metacarpal heads of humans and chimpanzees.
AB  - If Wolff's law is valid, then quantifying the three-dimensional architecture of
      trabecular bone, specifically 3D principal trabecular orientation (3D-PTO), can
      reveal joint loading direction among different taxa. This study measured the
      architecture of trabecular bone in the 3rd metacarpal head of humans and
      chimpanzees, and then tested their association with expected joint loading
      direction. We postulate that since chimpanzees, unlike humans, directly load
      their metacarpal bones during knuckle-walking, trabecular structure in the dorsal
      aspect of the 3rd metacarpal head will be significantly more organized and robust
      in chimpanzees. To test this hypothesis, we micro-CT scanned the 3rd metacarpal
      from 11 chimpanzees and 12 humans. Three 6 mm volumes of interest (VOI; palmar,
      center and dorsal) were selected and trabecular bone properties and 3D-PTO were
      measured. The results revealed many similarities between humans and chimpanzees:
      in both taxa the dorsal VOI demonstrated the lowest bone volume fraction (BV/TV),
      the most rod-like trabecular structure, the fewest and thinnest trabeculae, and
      low organization of the trabecular architecture (degree of anisotropy).
      Nevertheless, 3D-PTO in the dorsal VOI differed significantly between humans and
      chimpanzees. While 3D-PTO in humans was clustered together and aligned nearly
      along the bone long axis, in chimpanzees 3D-PTO was divided into two distinct
      groups and aligned with an angle toward either the medial or lateral
      orientations. Our results suggest that loading effects on trabecular bone
      properties such as BV/TV might be partially constrained by genetic factors. On
      the other hand, 3D-PTO is continually affected by active loading (i.e., modeling)
      and thus may serve as a useful tool to infer differences in joint loading
      directions.

PMID- 29054166
TI  - 3D enamel thickness in Neandertal and modern human permanent canines.
AB  - Enamel thickness figures prominently in studies of human evolution, particularly
      for taxonomy, phylogeny, and paleodietary reconstruction. Attention has focused
      on molar teeth, through the use of advanced imaging technologies and novel
      protocols. Despite the important results achieved thus far, further work is
      needed to investigate all tooth classes. We apply a recent approach developed for
      anterior teeth to investigate the 3D enamel thickness of Neandertal and modern
      human (MH) canines. In terms of crown size, the values obtained for both upper
      and lower unworn/slightly worn canines are significantly greater in Neandertals
      than in Upper Paleolithic and recent MH. The 3D relative enamel thickness (RET)
      is significantly lower in Neandertals than in MH. Moreover, differences in 3D RET
      values between the two groups appear to decrease in worn canines beginning from
      wear stage 3, suggesting that both the pattern and the stage of wear may have
      important effects on the 3D RET value. Nevertheless, the 3D average enamel
      thickness (AET) does not differ between the two groups. In both groups, 3D AET
      and 3D RET indices are greater in upper canines than in lower canines, and
      overall the enamel is thicker on the occlusal half of the labial aspect of the
      crown, particularly in MH. By contrast, the few early modern humans investigated
      show the highest volumes of enamel while for all other components of 3D enamel,
      thickness this group holds an intermediate position between Neandertals and
      recent MH. Overall, our study supports the general findings that Neandertals have
      relatively thinner enamel than MH (as also observed in molars), indicating that
      unworn/slightly worn canines can be successfully used to discriminate between the
      two groups. Further studies, however, are needed to understand whether these
      differences are functionally related or are the result of pleiotropic or genetic
      drift effects.

PMID- 29054168
TI  - Early evolutionary diversification of mandible morphology in the New World
      monkeys (Primate, Platyrrhini).
AB  - New World monkeys (order Primates) are an example of a major mammalian
      evolutionary radiation in the Americas, with a contentious fossil record. There
      is evidence of an early platyrrhine occupation of this continent by the Eocene
      Oligocene transition, evolving in isolation from the Old World primates from then
      on, and developing extensive morphological and size variation. Previous studies
      postulated that the platyrrhine clade arose as a local version of the Simpsonian
      ecospace model, with an early phase involving a rapid increase in morphological
      and ecological diversity driven by selection and ecological opportunity, followed
      by a diversification rate that slowed due to niche-filling. Under this model,
      variation in extant platyrrhines, in particular anatomical complexes, may
      resemble patterns seen among middle-late Miocene (10-14 Ma) platyrrhines as a
      result of evolutionary stasis. Here we examine the mandible in this regard, which
      may be informative about the dietary and phylogenetic history of the New World
      monkeys. Specifically, we test the hypothesis that the Simpsonian ecospace model
      applies to the platyrrhine mandible through a geometric morphometric analysis of
      digital images of the jaws of extant and extinct species, and we compare these
      results to those obtained using a phylogenetic comparative approach based on
      extant species. The results show a marked phylogenetic structure in the
      mandibular morphology of platyrrhines. Principal component analyses highlight the
      morphological diversity among modern forms, and reveal a similar range of
      variation for the clade when fossil specimens are included. Disparity-Through
      Time analysis shows that most of the shape variation between platyrrhines
      originated early in their evolution (between 20 and 15 Ma). Our results converge
      with previous studies of body mass, cranial shape, the brain and the basicranium
      to show that platyrrhine evolution might have been shaped by an early increase in
      morphological variation followed by a decelerated rate of diversification and
      evolutionary stasis.

PMID- 29054169
TI  - Phalangeal morphology of Shanghuang fossil primates.
AB  - Here, we describe hundreds of isolated phalanges attributed to middle Eocene
      fossil primates from the Shanghuang fissure-fillings from southern Jiangsu
      Province, China. Extending knowledge based on previous descriptions of
      postcranial material from Shanghuang, this sample of primate finger and toe bones
      includes proximal phalanges, middle phalanges, and over three hundred nail
      bearing distal phalanges. Most of the isolated proximal and middle phalanges fall
      within the range of small-bodied individuals, suggesting an allocation to the
      smaller haplorhine primates identified at Shanghuang, including eosimiids. In
      contrast to the proximal and middle phalanges from Shanghuang, there are a
      variety of shapes, sizes, and possible taxonomic allocations for the distal
      phalanges. Two distal phalangeal morphologies are numerically predominant at
      Shanghuang. The sample of larger bodied specimens is best allocated to the medium
      sized adapiform Adapoides while the smaller ones are allocated to eosimiids on
      the basis of the commonality of dental and tarsal remains of these taxa at
      Shanghuang. The digit morphology of Adapoides is similar morphologically to that
      of notharctines and cercamoniines, while eosimiid digit morphology is unlike
      living anthropoids. Other primate distal phalangeal morphologies at Shanghuang
      include grooming "claws" as well as specimens attributable to tarsiids,
      tarsiiforms, the genus Macrotarsius, and a variety of adapiforms. One group of
      distal phalanges at Shanghuang is morphologically indistinguishable from those of
      living anthropoids. All of the phalanges suggest long fingers and toes for the
      fossil primates of Shanghaung, and their digit morphology implies arboreality
      with well-developed digital flexion and strong, grasping hands and feet.

PMID- 29054170
TI  - Morphological description and morphometric analyses of the Upper Palaeolithic
      human remains from Dzudzuana and Satsurblia caves, western Georgia.

PMID- 29054171
TI  - The evolution of human sleep: Technological and cultural innovation associated
      with sleep-wake regulation among Hadza hunter-gatherers.
AB  - Sleep is necessary for the survival of all mammalian life. In humans, recent
      investigations have generated critical data on the relationship between sleep and
      ecology in small-scale societies. Here, we report the technological and social
      strategies used to alter sleep environments and influence sleep duration and
      quality among a population of hunter-gatherers, the Hadza of Tanzania.
      Specifically, we investigated the effects that grass huts, sound levels, and fire
      had on sleep. We quantitatively compared thermal stress in outdoor environments
      to that found inside grass hut domiciles to test whether the huts function as
      thermoregulated microhabitats during the rainy season. Using physiological
      equivalent temperature (PET), we found that the grass huts provide sleep sites
      with less overall variation in thermal stress relative to outside baseline
      environments. We also investigated ambient acoustic measures of nighttime
      environments and found that sound significantly covaried with sleep-wake
      activity, with greater sound levels associating with less sleep. Finally, after
      controlling for ecological variables previously shown to influence sleep in this
      population, fire was shown to neither facilitate nor discourage sleep expression.
      Insofar as data among contemporary sub-tropical foragers can inform our
      understanding of past lifeways, we interpret our findings as suggesting that
      after the transition to full time terrestriality, it is likely that early Homo
      would have had novel opportunities to manipulate its environments in ways that
      could have significantly improved sleep quality. We further conclude that control
      over sleep environment would have been essential for migration to higher
      latitudes away from equatorial Africa.

PMID- 29054172
TI  - Editorial comment: Obesity in America.

PMID- 29054173
TI  - American Society for Metabolic and Bariatric Surgery updated position statement
      on sleeve gastrectomy as a bariatric procedure.

PMID- 29054174
TI  - Long-term nutritional impact of sleeve gastrectomy.
AB  - BACKGROUND: Sleeve gastrectomy (SG) has become a predominant bariatric procedure
      throughout the world. However, the long-term nutritional impact of this procedure
      is unknown. OBJECTIVES: To describe the nutritional deficiencies before and after
      SG and to analyze the influence of baseline weight on nutritional status.
      SETTING: University-affiliated tertiary care center. METHODS: All patients who
      underwent SG as a standalone procedure between 2008 and 2012 were included in
      this study. Patients were given multivitamin supplementation. Data were obtained
      from our prospectively maintained electronic database and are reported as mean +/
      standard deviation and percentage. Bivariate analyses were conducted to evaluate
      the influence of selected variables on outcomes. RESULTS: The mean age of the 537
      patients was 48.0 +/- 11.3 years, with an initial body mass index of 48.1 +/- 8.7
      kg/m2. Excess weight loss and total weight loss were 56.2% and 28.0% at 1 year
      and 43.0% and 21.1% at 5 years, respectively (P<.0001). Percentage of follow-up
      was 74% at 5 years (n = 79). The mean follow-up time was 34.3 +/- 17.2 months.
      Hypoalbuminemia was present in 1.1% preoperatively and 4.2% at 5 years (P =
      .0043), low ferritin levels in 8.6% and 37.8% (P<.0001), low vitamin B12 in 30.3%
      and 16.4% (P<.0001), low vitamin D 63.2% and 24.3% (P<.0001), and
      hyperparathyroidism in 23.4% and 20.8% (P<.0001). There was no significant
      difference in the prevalence of anemia over time (P = 0.4301). The prevalence of
      vitamin A insufficiency peaked from 7.9% preoperatively to 28.7% at 3 months
      (P<.0001) and returned to baseline thereafter. Baseline weight was negatively
      correlated with vitamin B12 and vitamin D. CONCLUSION: Nutritional deficiencies
      are common in patients with morbid obesity before and after surgery. Preoperative
      supplementation and long-term nutritional follow-up are required to prevent
      nutritional deficiencies.

PMID- 29054175
TI  - Effect of Roux-en-Y gastric bypass on thyroid function in euthyroid patients with
      obesity and type 2 diabetes.
AB  - BACKGROUND: The impact of bariatric surgery on thyroid hormone levels is poorly
      understood. OBJECTIVES: To investigate changes in serum-free thyroxine (FT4) and
      thyroid-stimulating hormone (TSH) after Roux-en-Y gastric bypass (RYGB) in
      euthyroid patients with obesity and type 2 diabetes. SETTING: University
      Hospital, China. METHODS: Eighty-one euthyroid Chinese patients with obesity and
      type 2 diabetes who underwent RYGB, and 20 healthy volunteers were enrolled in
      this retrospective study. Participants were evaluated for changes in
      anthropometric parameters, metabolic indexes, FT4, and TSH at baseline and 6
      months after surgery. Multiple linear regression analysis was used to identify
      factors that could predict changes in FT4 and TSH. RESULTS: Mean FT4 levels
      decreased from 16.26-14.59 pmol/L (P<.01), while TSH levels decreased
      significantly (2.19+/-1.09 mIU/L versus 1.97+/-1.12 mIU/L, P = .027) 6 months
      postsurgery. Multiple linear regression analysis showed that the waist/hip ratio
      (beta =-7.406, P = .031) and duration of diabetes (beta =-.087, P = .009) were
      independent factors contributing to this decrease in FT4 levels. Moreover,
      changes in TSH levels were significantly and positively correlated with 2-hour
      postprandial blood glucose at patient baseline (beta = .064, P< .01).
      CONCLUSIONS: The present study is the first to show that both serum levels of FT4
      and TSH decrease after RYGB in euthyroid patients with obesity and type 2
      diabetes. Our results suggest that not only can RYGB improve metabolic
      abnormalities, but it may also alter the feedback regulation of the thyroid
      system.

PMID- 29054176
TI  - SOARD Category 1 CME Credit Featured Articles,Volume 13, October 2017.

PMID- 29054177
TI  - What is the ideal fibrinolysis to PCI time: Pharmaco-invasive strategy with
      streptokinase?

PMID- 29054178
TI  - Graft Spasm-The Achilles Heel of Arterial Grafts.

PMID- 29054179
TI  - The impact of systems-of-care on pharmacoinvasive management with streptokinase:
      The subgroup analysis of the TN-STEMI programme.
AB  - OBJECTIVES: We evaluated the impact of implementation of the TN-STEMI programme
      on various characteristics of the pharmacoinvasive group by comparing clinical as
      well as angiographic outcomes between the pre- and post-implementation groups.
      METHODS: The TN-STEMI programme involved 2420 patients of which 423 patients had
      undergone a pharmacoinvasive strategy of reperfusion. Of these, 407 patients had
      a comprehensive blinded core-lab evaluation of their angiograms post-lysis and
      clinical evaluation of various parameters including time-delays and adverse
      cardio- and cerebro-vascular events at 1year. Streptokinase was used as the
      thrombolytic agent in 94.6% of the patients. RESULTS: In the post-implementation
      phase, there was a significant improvement in 'First medical contact (FMC)-to
      ECG' (11 vs. 5min, p<0.001) and 'Lysis-to-angiogram' (98.3 vs. 18.2h, p<0.001)
      times. There was also a significant improvement in the number of coronary
      angiograms performed within 24h (20.7% vs. 69.3%, p<0.001). The 'Time-to-FMC'
      (160 vs. 135min, p=0.07) and 'Total ischemic time' (210 vs. 176min, p=0.22) also
      showed a decreasing trend. IRA patency rate (70.2% vs. 86%, p<0.001) and thrombus
      burden (TIMI grade 0: 49.1% vs. 73.4%, p<0.001) were superior in this group. The
      MACCE rates were similar except for fewer readmissions (29.8% vs. 12.6%,
      p=0.0002) and target revascularizations at 1year (4.8% vs. none, p=0.002) in the
      post-implementation group. CONCLUSION: The implementation of a system-of-care
      (hub-and-spoke model) in the pharmacoinvasive group of the TN-STEMI programme
      demonstrated shorter lysis-to-angiogram times, better TIMI flow patterns and
      lower thrombus burden in the post-implementation phase.

PMID- 29054180
TI  - Meta-analysis comparing radial versus femoral approach in patients 75 years and
      older undergoing percutaneous coronary procedures.
AB  - INTRODUCTION: Elderly patients (>=75 years) undergoing coronary angioplasty are
      increasing. Meta-analyses have shown the benefits of radial access which might
      reduce hospital stay by decreasing access site complications with associated
      secondary benefits, however, the population over the age of 75 years were not a
      large part of the cohort and may behave differently due to increased
      atherosclerotic burden and age-related vascular changes. In addition,
      complications unique to this age group such as delirium and deconditioning might
      occur which could have a bearing on the outcome. METHODS: We searched Pubmed,
      SCOPUS, Medline, Dynamed, Cochrane. The search terms used were femoral and
      radial, femoral versus radial, radial or femoral access site, radial or femoral
      comparison. There were no restrictions. RESULTS: There was a significant decrease
      (85%)in the incidence of access site complications in the radial group. The time
      to achieve ambulation was lower by 14.25h (8.86-19.56h). However, the incidence
      of crossover (in effect failure to perform catheterization by radial access) from
      radial to femoral was significantly higher. Radial access was associated with
      longer procedural times (2.75min) and increased contrast dose however, there was
      no statistical difference in the fluoroscopy time between the two. CONCLUSIONS:
      Radial access has similar benefits in elderly patients as those under the age of
      75 and may be beneficial in patients at risk of delirium or deconditioning.
      However, crossover rates, contrast dose and procedure time were higher. It is
      conceivable that as experience is gained, these rates will diminish.

PMID- 29054181
TI  - Clinico-angiographic profile and procedural outcomes in patients undergoing
      percutaneous coronary interventions: The Srinagar registry.
AB  - BACKGROUND: This study was aimed at exploring the clinical profile, angiographic
      characteristics and procedural outcomes in patients undergoing PCI at our
      institute. METHODS: This prospective observational study included all consecutive
      patients who underwent PCI at our hospital between January 2014 and December
      2015. Data including clinico-demographic profile, angiographic details and lesion
      characteristics were recorded in all patients. Procedural details including
      devices and drugs used, procedure related complications, and in-hospital outcomes
      of these patients were analysed. RESULTS: A total of 624 patients (mean age-
      59.30+/-11.17years) with 84.8% males and 15.2% females were included in the
      study. Smoking and hypertension were the most common risk factors, present in
      79.8% and 74.8% patients respectively. Diabetes mellitus, dyslipidemia, and
      obesity were observed in 24.5%, 26.1%, and 25.0% patients respectively. Anterior
      wall MI was the most common mode of presentation (32.1%). Single Vessel Disease
      (SVD) was most common angiographic pattern, observed in 50.3% patients; left
      anterior descending artery (LAD) was the most frequently involved vessel (65.9%);
      and type B lesions were most prevalent (52.3%). Most of the procedures were
      elective (61.4%) and femoral route was used in the majority (82.6%). Drug eluting
      stents were deployed in 99.1% of the cases. The overall procedural success rate
      was 93.6%. Procedural mortality was 1.0% and periprocedural complications
      occurred in 9.9% patients. CONCLUSION: This first prospective PCI registry from
      the state of Jammu & Kashmir provides an insight into the patterns of CAD among
      Kashmiri population, and highlights the spectrum of PCIs performed with their
      outcomes.

PMID- 29054182
TI  - Clinical outcome in nonagenarians undergoing transcatheter valve replacement.
AB  - BACKGROUND: Nonagenarians are mostly denied from different therapeutic strategies
      due to high preoperative risk. We present the results of nonagenarians with
      severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement
      (TAVR). METHODS: Our retrospective analysis include baseline and procedural data
      along with clinical outcome. Clinical follow-up was performed in all patients
      after TAVR. RESULTS: Out of 689 patients, 33 nonagenarians with a mean age of
      90.9+/-1.4years suffering from severe AS and elevated comorbidity index (logistic
      EuroSCORE of 16.3+/-9.6%, STS score 11.1+/-9.9%) underwent TAVR between September
      2009 and July 2016 using self-expanding prosthesis. Baseline transthoracic
      echocardiography reported a mean aortic valve area (AVA) of 0.64+/-0.12cm2 with a
      mean pressure gradient of 56.1+/-16.1mmHg. Five (16.2%) patients had
      postprocedural moderate/severe aortic regurgitation. One patient died
      intraoperally due to ventricular perforation during predilatation, while two
      patients died within the first 30days, one due to cardiogenic shock and the other
      due to pneumonia. No patient experienced a myocardial infarction or a stroke,
      while ten (30.3%) required permanent pacemaker placement. At follow-up (mean 20.3
      months, range 1-78 months), all cause and cardiovascular mortality was 24.2% and
      15.1%, respectively. Two patients presented heart failure and 12 (40%) had
      exertional dyspnea. By echo, mean valve area was 1.72+/-0.12cm2 and mean gradient
      11.2+/-1.4mmHg. Two patients (16.7%) presented moderate aortic regurgitation.
      CONCLUSION: Our case series demonstrate that even with elevated comorbidity
      index, clinical endpoints and valve-associated results are relatively favorable
      in nonagenarians treated with TAVR.

PMID- 29054183
TI  - Appropriateness of elective percutaneous coronary intervention and impact of
      government health insurance scheme - A tertiary centre experience from Western
      India.
AB  - BACKGROUND: There is a dearth of data regarding the appropriateness of elective
      percutaneous coronary intervention (PCI) in a limited-resource country such as
      India. In an attempt to rationalise the use of PCI, Appropriate Use Criteria
      (AUC) were developed for cardiovascular care in the USA. In the Indian context,
      considering the high prevalence of coronary artery disease, the dramatic rise in
      the number of revascularization procedures and an increasing role of
      government/private reimbursements, application of AUC could potentially guide
      policy to optimize the utilization of resources and the benefit-risk ratio for
      individual patients. OBJECTIVES: The study sought to determine the overall and
      year-wise trends in the appropriateness of elective PCI using the AUC and also
      understand the impact of the government health insurance scheme (GHIS). MATERIAL
      AND METHODS: The inpatient records of all patients undergoing elective PCI, at a
      single large tertiary care centre in Western India, from January 2009 to December
      2014 were retrospectively analysed (n=972, 759 males, 213 females) by a neutral
      observer. The AUC scores and subsequent ranking were calculated using the
      dedicated web-based software and each PCIwas ranked as either 'appropriate',
      'uncertain' or 'inappropriate'. Elective PCI performed within a month after the
      index acute coronary syndrome (ACS) was considered as 'ACS' while applying the
      AUC. All other indications were considered as 'non-ACS'. Nearly 95% of elective
      PCI performed after July 2012 were covered under theGHIS and therefore the period
      January 2009-June 2012 was compared with the July 2012- December 2014 to assess
      the impact of this scheme. RESULTS: A total of 894 elective PCI (379 and 515 PCI
      in the ACS setting and non-ACS setting respectively) performed on 857 patients
      were analysed. The elective PCI performed in the pre-GHIS and GHIS period were
      458 and 436 respectively. As per AUC, 352 (39.6 +/- 4.4 %) of the overall
      elective PCI were ranked as 'appropriate', while 487 (55.3 +/- 4.1 %) cases as
      'uncertain' and 55 (5.1 +/- 0.6 %) cases as 'inappropriate'. An overall year-wise
      temporal trend in the proportion of cases in any of the AUC rankings did not show
      any significant trends(p > 0.05). However, 80.4 +/- 7.3 % of elective PCI in the
      ACS setting were categorised as 'appropriate' and 82.6 +/- 6.9 % of elective PCI
      in non-ACS setting were ranked as 'uncertain'. With state-wide implementation of
      the GHIS, the total number of elective PCI increased by 50% (436 in the 31/2 year
      pre-GHIS study period as against 458 in the 21/2 year GHIS study period). The
      introduction of GHIS led to a marginal increase (p > 0.05) in the average annual
      number of elective PCI in non-ACS setting as opposed to a 120% rise in the number
      of elective PCI done in the ACS setting (p < 0.001) and the delay in performing
      PCI after coronary angiogram reduced from 55.8 +/- 43.6 days to 33 +/- 22.9 days
      (p < 0.01). Also, the ratio of men: women undergoing elective PCI rationalised
      from 5.4:1 to 2.7:1 (p < 0.001). With the introduction of the GHIS, the share of
      'inappropriate' elective PCI in the ACS setting increased from 1.34 % to 4.81 %
      (p =0.065). However, there was also a fall in 'appropriate' elective PCI in the
      non-ACS setting from 15.0 +/- 3.2% to 7 +/- 1.6% (p < 0.001). CONCLUSION: On
      applying the 2012 updated AUC, about 5 % of overall elective PCI were deemed as
      'inappropriate'. About four in every five elective PCI in the non-ACS setting
      were of 'uncertain' appropriateness. The implementation of the GHIS not only
      significantly reduced the gender bias and delay in seeking interventional
      coronary care but also led to a significant rise in the proportion of PCI
      performed in the ACS setting. However, there was also a rise in 'inappropriate'
      PCI in the ACS setting and a significant fall in 'appropriate' PCI in the non-ACS
      setting after introduction of the GHIS..

PMID- 29054184
TI  - Under-utilization of pacemaker therapy for sinus node dysfunction - Real world
      data from South Asia.
AB  - OBJECTIVE: Chronic symptomatic sinus node dysfunction (SND), the most common
      bradyarrhythmia, can be effectively managed by permanent cardiac pacing. Yet the
      care pathway and barriers to adoption of pacing therapy are not well understood -
      particularly in low volume implanting countries. The IMPROVE Brady study is a
      quality improvement initiative being conducted at centers in South Asia, Latin
      America, and Russia. We assessed the rates of SND diagnosis and pacemaker
      treatment for SND in the South Asia cohort. METHODS: The prospective study
      enrolled patients with heart rate of  <=50 beats per minute presenting with
      symptoms including syncope, dizziness, and/or dyspnea from ten centers in India
      and Bangladesh. Patients were followed to identify the proportion diagnosed with
      SND and subsequently treated with pacemaker therapy. RESULTS: A total of 508
      patients meeting criteria were enrolled and followed on average for 8.3+/
      8.0months. Patients were on average 58 years of age, 77% were male, and 91% had
      completed at least primary education. An SND diagnosis was made in 368 (72%) of
      patients, with the majority (80%) of diagnoses occurring within 1 month of
      enrollment. Of the patients with an SND diagnosis, 63 (17%) were treated with a
      pacemaker. Reasons for not receiving treatment were: subject refusal or deferred
      decision (45%), unaffordability (34%), physician determined - not-indicated
      (20%), and other (1%). Older age, female gender, history of hypertension, lower
      resting heart rate, and syncopal or pre-syncopal symptoms were associated with a
      higher probability of implant. CONCLUSIONS: In a care pathway assessment for the
      diagnosis and treatment of symptomatic SND in South Asia only 1 in 6 patients
      received pacemaker indicated therapy, largely due to patient refusal and
      physician decision. Phase II of the study will be aimed to improve this treatment
      rate.

PMID- 29054185
TI  - The prognostic significance of serum sodium in a population undergoing cardiac
      resynchronisation therapy.
AB  - PURPOSE: To determine the prognostic implications of changes towards hyponatremia
      at varying time-points in the treatment of patients undergoing cardiac
      resynchronisation therapy (CRT). METHODS: A retrospective series of 249 patients
      was studied from 2002 to 2013. The population was categorized on the basis of
      serum sodium profile at baseline, at 1 month and at 6 month follow up visits
      following successful CRT implantation. The composite endpoint was all-cause
      mortality and heart failure hospitalisation (defined by the need for intravenous
      diuretic therapy) following CRT implantation. RESULTS: A total of 249 patients
      (67.8+/-12.5 years; NYHA class III/IV 75; LVEF 27.2+/-8.8%) were followed up for
      a median of 5.5 years. Hyponatremia at baseline, 1 month or 6 months follow up
      did not predict the composite endpoint. 26% of patients showed hyponatremia at
      baseline prior to CRT implantation, while it was present in 19.9% of patients 1
      month (p=0.003) and in 16% (p<0.001) 6 months after CRT implantation. There was a
      significantly worse outcome for those patients who developed hyponatremia 6
      months after CRT implantation. In multivariate analysis, the intake of loop
      diuretics (HR 1.76 [1.04-2.95], p=0.03) and renal impairment (urea>7.0mmol/l) (HR
      1.61 [1.05-2.46], p=0.03) at baseline were associated with an increased risk of
      unplanned heart failure hospitalisation and all-cause mortality after CRT
      implantation. CONCLUSIONS: A change towards hyponatremia when observed 6 months
      after CRT implantation may predict a worse clinical outcome. Additionally, renal
      impairment and higher diuretic doses are associated with an increased risk of
      mortality in the population analysed.

PMID- 29054186
TI  - Isolated coronary artery ectasia: Clinical, angiographic, and follow up
      characteristics.
AB  - BACKGROUND: Isolated Coronary artery ectasia (CAE) is considered an uncommon
      angiographic finding with varying patterns of presentation and carries
      significant morbidity burden to the patient. Our objective was to evaluate the
      prevalence of this condition, to analyse its clinical, angiographic, and follow
      up characteristics. PATIENTS AND METHODS: Coronary angiography was performed in
      4950 patients from January 2009 to August 2014. The epidemiological, clinical,
      angiographic, and follow up characteristics of 52 patients with isolated CAE were
      examined. RESULTS: Of the 4950 angiograms analysed, isolated CAE was found in 52
      patients, a prevalence of 1.05 %. The mean age of patients was 53.4 years. A
      predominance of the male sex was observed (71.1%). Angina on exertion was the
      most common presenting symptom (61.5%). Single vessel was involved in 61.5%. Left
      anterior descending artery was the most commonly involved vessel followed by
      right coronary artery, left circumflex and left main coronary artery. Type IV CAE
      as per Markis classification was the most common involvement. The median follow
      up was 28+/-20 months, during which 10 patients (19.2%) had recurrent chest pain,
      and four patients were re-hospitalised, three for unstable angina, one for
      myocardial infarction. CONCLUSION: The prevalence of isolated coronary ectasia
      was 1.05%. The majority of patients had single vessel involvement, and left
      anterior descending branch was the most common involved vessel. This condition
      may not be considered completely benign, as it is associated with atherosclerotic
      risk factors and occurrence of coronary events including angina and myocardial
      infarction.

PMID- 29054187
TI  - Accuracy of exercise tolerance test in the diagnosis of coronary artery disease
      in patients with left dominant coronary circulation.
AB  - BACKGROUND: Exercise is a physiologic stress that helps the physicians to clarify
      the presence or absence of cardiovascular disease which may be obscure at rest.
      Although it is sensitive, its specificity is affected by several parameters, such
      as some metabolic conditions, some structural heart diseases, and some baseline
      electrocardiogram abnormalities. Currently, the relationship between coronary
      dominance and accuracy of EET is not examined. Therefore, this study was
      conducted to determine the potential impact of coronary dominance on the accuracy
      of EET. METHODS: In this retrospective study, data were gathered from 720
      patients from four medical centers. The pattern of dominancy was determined, and
      the coronary dominance pattern of the patients who had normal angiograms despite
      abnormal EETs was compared to that from all the patients. RESULTS: Among the
      patients who had a normal angiogram despite an abnormal EET, 27% were left
      dominant while the frequency of left dominancy in the whole population of the
      study was only 10.9% (P=0.013). There were no significant differences in baseline
      characteristics, such as age and sex, between the two studied groups. CONCLUSION:
      The results indicated that the presence of left dominance in patients who had
      normal angiograms despite an abnormal EET was significantly higher than general
      population. Therefore, left dominance may be considered a confounding factor for
      EET, producing false positive results.

PMID- 29054188
TI  - Effect of thrombolytic therapy on the patterns of post myocardial infarction
      ventricular septal rupture.
AB  - OBJECTIVES: Ventricular septal rupture (VSR) is a rare but feared complication
      after myocardial infarction (MI). The objective of this study was to investigate
      the effects of thrombolytic therapy on the patterns of VSR following MI. METHODS:
      30 consecutive patients admitted to a single tertiary level cardiac hospital with
      a diagnosis of acute MI and developed VSR in the hospital were included. The
      effect on thrombolytic therapy on the formation of VSR and its clinical outcome
      was studied. RESULTS: Out of 30 patients, 15 patients received thrombolytic
      therapy.10 received early (<12h) and 5 received late (>12h). The median time to
      post MI VSR formation was significantly shorter in thrombolysis group compared to
      non thrombolysis group at 1 vs 3 days(p=0.026). The median time for VSR formation
      was shorter in early thrombolysis group compared to late thrombolysis group at 1
      vs 3 days (p=0.022). There was no difference between late and no thrombolytic
      therapy (3 vs 3 days, p=0.672). There was no significant difference in the
      mortality between thrombolytic and no thrombolytic therapy (p=0.690). Patients
      treated medically had a significant higher mortality compared to patients treated
      surgically (p=0.005). CONCLUSION: Thrombolytic therapy results in an earlier
      presentation of VSR after MI. This earlier presentation may be due to reduction
      in the number of patients developing late VSR after thrombolytic therapy, while
      the number of patients developing an early VSR remaining unaffected. Despite
      improvements in medical therapy and percutaneous and surgical techniques,
      mortality with this complication remains extremely high.

PMID- 29054189
TI  - Development of a diagnosis model for coronary artery disease.
AB  - BACKGROUND: The purpose of this study was to develop a coronary artery disease
      (CAD) prediction model that optimally estimates the pre-test probability of CAD
      for patients suspected of CAD. METHODS AND RESULTS: This retrospective, multi
      centre study included 7360 consecutive patients (4678 men, 57.87+/-11.42 years
      old; 2682 women, 61.60+/-9.58 years old) who underwent coronary angiography for
      evaluation of CAD. A prediction model was fitted for diagnosis of CAD with the
      help of eight significant risk factors including sex, age, smoking status,
      diabetes, hypertension, dyslipidaemia, serum creatinine and angina. All potential
      predictors were significantly associated with the presence of CAD. The prevalence
      of CAD was significantly higher in men than in women. The clinical model gives a
      relatively accurate prediction of CAD with an area under the curve (AUC) of 0.74
      (95% CI, 0.88-0.96; P<0.001). Addition of angina to the prediction model improves
      the predictive precision of the model. The optimal cut-off for predicting CAD in
      this model was 0.79 with a sensitivity of 0.658 and a specificity of 0.709.
      CONCLUSION: A prediction model including age, sex, and cardiovascular risk
      factors allow for an accurate estimation of the pre-test probability of coronary
      artery disease in Chinese populations. This algorithm may be useful in making
      decisions relating to the diagnosis of CAD.

PMID- 29054190
TI  - Bilateral internal thoracic artery grafting in India-Time to raise the bar.
AB  - OBJECTIVES: Bilateral internal thoracic artery (BITA) grafting strategy is the
      current trend in coronary artery bypass grafting for multivessel coronary artery
      disease. Although better long-term outcomes have been shown, BITA grafting is
      underutilized as a main strategy for revascularization by most of the surgeons.
      The survey was conducted to ascertain the current usage and concerns of BITA
      grafting in India. METHODS: Database of 856 Indian cardiac surgeons currently
      with predominantly adult practice was prepared and a questionnaire was sent about
      use of single and bilateral ITA grafts and BITA grafting strategy in different
      clinical scenarios. RESULTS: A total of 112 surgeons (13.08%) from 75
      institutions responded and 92 surgeons (10.7%) completed the survey. Single ITA
      is used by 79% of surgeons in more than 90% of their patients. 31% and 29% of
      surgeons use BITA grafting in 5-10% and 11-98% of their patients respectively.
      53% of surgeons avoided the usage of BITA grafting in patients with smoking, 35%
      of surgeons in chronic obstructive pulmonary disease, 58% of surgeons in obesity
      and 62% of surgeons in acute coronary syndrome, 36% of surgeons in patients with
      left ventricular dysfunction and 61% of surgeons in patients with poor coronary
      anatomy. The concerns for BITA usage are risk of deep sternal wound infection
      (DSWI) (40%), increased operative time (27%), unknown superiority (12%) and
      limited length of right ITA (5%). CONCLUSIONS: The usage of BITA grafting is
      restricted to 10% in India and main concerns are DSWI and increased operative
      time.

PMID- 29054191
TI  - Comparing short and long term survival of patients undergoing off pump coronary
      artery bypass graft with and without coronary endarterectomy.
AB  - BACKGROUND AND AIM: There is some controversy about survival of coronary
      endarterectomy (CE) patients, so the current study aims to compare short and long
      term survival of patients undergoing off pump coronary artery bypass graft
      (OPCAB) with and without coronary endarterectomy. PATIENTS AND METHODS: we
      performed a retrospective analysis of data on patients undergoing OPCAB and CE
      between 2011 and 2012. Preoperative, perioperative and postoperative data
      collected from data bank. Follow-up information was obtained from telephone
      contact mean time 37.13+/-23.82months after surgery. Early and late outcomes were
      compared by univariate and Kaplan-Meier analysis. RESULT: OPCAB was performed in
      474 patients, which 69 of them had a CE. The mean long term survival was similar
      between OPCAB (56.28+/-0.61) and OPCAB+CE (55.54+/-1.3) groups (p=0.66). Multiple
      Cox regression shows that age, gender, BMI, EF and angina were significant
      predictors of mortality. Patients undergoing CE have a long term intensive care
      unit (ICU) stay (51.31+/-5.59 vs 37.23+/-0.88, P=0.015) and blood transfusion was
      higher in CE group (650.62+/-110 vs. 324.71+/-22, P=0.001). CONCLUSION: The
      current study demonstrates that results of CE are acceptable with respect to
      short and long -term survival. Patients undergoing CE required long term ICU stay
      and higher blood transfusion.

PMID- 29054192
TI  - Early and aggressive ISR with a polymer- and carrier-free drug-coated stent
      system.
AB  - The LEADERS FREE trial concluded that the polymer free drug-coated BioFreedomTM
      stent appeared to be both safer and more effective than bare-metal stents (BMS)
      with an ISR rate comparable to traditional DES without the need for prolonged
      DAPT. We implanted 45 BioFreedomTM stents in 34 patients over a 4-month period. 4
      patients represented early (106-238 days after the implant procedure) with angina
      symptoms and severe ISR was detected in all patients. The rate of severe and
      early ISR detected in our patient population of 11.8% is comparable to that of
      traditional BMS. Further studies are warranted.

PMID- 29054193
TI  - Polymorphisms of cytochrome P450 are potential candidates that could potentially
      help clinicians on the treatment of cardiovascular diseases among Asian
      populations.
AB  - There are significant ethnic differences in the metabolism of some drugs that can
      be explained by cytochrome P450 polymorphisms and, in particular, the CYP2D6
      isozyme. In addition, among patients who are not carriers of the CYP2C19 loss-of
      function alleles, there is a reduced risk of stroke when clopidogrel is taken
      with aspirin compared to aspirin alone. These findings demonstrate that there is
      inter-ethnic variability in the metabolism of some drugs, which results in
      different responses to cardiovascular drugs in Asian versus non-Asian
      populations.

PMID- 29054194
TI  - Contrast filled bulge inside the aortic root.

PMID- 29054195
TI  - Coronary artery disease in high risk South Asian immigrants: Role of
      dysfunctional HDL in risk prediction.

PMID- 29054196
TI  - Rare case of massive pericardial effusion secondary to primary
      hypoparathyroidism.

PMID- 29054197
TI  - Implantable cardioverter-defibrillator (ICD) provides an exclusive
      epidemiological tool for evaluation of the earthquake induced cardiac
      arrhythmias.

PMID- 29054198
TI  - Mycotic aneurysm of the left anterior descending coronary artery induced by
      'mother-and-child' catheter assisted percutaneous coronary angioplasty!

PMID- 29054199
TI  - Ivabradine for junctional ectopic tachycardia in post congenital heart surgery.
AB  - We report two cases of malignant junctional ectopic tachycardia (JET), in infants
      following congenital heart surgery. After the failure of conventional therapy the
      arrhythmia was controlled by oral Ivabradine, a drug which is routinely used to
      lower heart rate in angina and heart failure in adult practice.

PMID- 29054200
TI  - The role of acute circulatory support in ST-segment elevation myocardial
      infarction complicated by cardiogenic shock.
AB  - In the setting of ST-segment elevation myocardial infarction (STEMI) complicated
      by cardiogenic shock, three primary treatment objectives include providing
      circulatory support, ventricular unloading, and restoring myocardial perfusion.
      In addition to primary percutaneous coronary intervention, each of these three
      objectives can be achieved with appropriate use of an acute mechanical
      circulatory support (AMCS) pump. Over the past decade, utilization of
      percutaneously-delivered AMCS devices including the Impella axial-flow catheter,
      TandemHeart left atrial-to-femoral artery bypass system, and veno-arterial
      extracorporeal membrane oxygenation (VA-ECMO) has grown exponentially. In this
      review, we will discuss the hemodynamic impact of each AMCS device and clinical
      data surrounding their use in the setting of STEMI complicated by cardiogenic
      shock.

PMID- 29054201
TI  - Electrocardiographic features: Various atrial site pacing.
AB  - Atrial pacing is done for either symptomatic sinus node dysfunction (SND) or for
      maintenance of atrio-ventricular synchrony in a dual chamber pacemaker.
      Conventionally, atrial lead is placed in the right atrial appendage. Atrial
      conduction disorder in patients with permanent pacing results in higher incidence
      of atrial fibrillation. Atrial septal pacing has emerged as a solution to this
      problem. So, it is extremely important to understand the different features of
      paced P wave from various atrial pacing sites. Conventional right atrial
      appendage pacing in presence of atrial conduction disorder results in marked
      latency with prolonged P wave duration with reduced amplitude. The morphology is
      similar to sinus rhythm. Atrial septal pacing causes short and sharp P wave with
      negative polarity in inferior leads and positive polarity in lead V1 in lower
      septal pacing, whereas positive polarity in inferior leads and negative polarity
      in lead V1 during pacing from upper septum.

PMID- 29054202
TI  - 'Heart Team' Concept - A reality or a 'Platonic Illusion'.
AB  - Post Syntax Trial, 'Heart Team' Concept has been ensconsed class I recommendation
      in both the European and ACC/AHA guidelines and has gained increasing traction in
      context of complex and multi modality procedures. Despite an arrray of advantages
      including the much touted - 'the patient is central', there are a plethora of un
      addressed issues, some of which sentinel to our country, which threaten to make
      the 'Heart Team' concept a perfunctory exercise. As it stands today, 'Heart Team'
      is more of a fictional euphemism, a kind of 'Platonic Illusion' rather than a
      pragmatic reality.

PMID- 29054203
TI  - Practice of medicine at the crossroads. Regarding: Mishra S. Our intellectuals
      have failed us - system of a down. Indian Heart J. 2017;69 (March-April (2)):133
      135.

PMID- 29054204
TI  - Electroceuticals in medicine - The brave new future.
AB  - Electroceuticals are a new category of therapeutic agents which act by targeting
      the neural circuits of organs. The therapy involves mapping the neural circuitry
      and delivering neural impulses to these specific targets. The impulse is
      administered via an implantable device. In cardiology besides pacemaker,
      defibrillation and resynchronization applications it could have usefulness in
      heart failure, atrial fibrillation, coronary artery disease, myocarditis,
      resistant hypertension, atrial and ventricular tachyarrhythmias, pulseless
      electrical activity, and refractory angina.

PMID- 29054205
TI  - Corrigendum to "Administration of low molecular weight and unfractionated heparin
      during percutaneous coronary intervention" [Indian Heart J. 68 (2) (2016) 213
      224].

PMID- 29054206
TI  - Corrigendum to "Cardiac resynchronization therapy in patients with mild heart
      failure is a reversal therapy" [Indian Heart J. 69 (1) (2017) 112-118].

PMID- 29054207
TI  - Degrees of Belief and the Burden of Proof: The ART Trial.

PMID- 29054208
TI  - Invited Commentary.

PMID- 29054209
TI  - Nikaidoh Procedure: How I Teach It.

PMID- 29054211
TI  - Invited Commentary.

PMID- 29054210
TI  - The Society of Thoracic Surgeons General Thoracic Surgery Database: 2017 Update
      on Research.
AB  - The outcomes research efforts based on The Society of Thoracic Surgeons (STS)
      General Thoracic Surgery Database include two established research programs with
      dedicated task forces and with data analyses conducted at the STS data analytic
      center: (1) The STS-sponsored research by the Access and Publications program,
      and (2) grant and institutionally funded research by the Longitudinal Follow-Up
      and Linked Registries Task Force. Also, the STS recently introduced the research
      program enabling investigative teams to apply for access to deidentified patient
      level General Thoracic Surgery Database data sets and conduct related analyses at
      their own institution. Last year's General Thoracic Surgery Database-based
      research publications and the new Participant User File research program are
      reviewed.

PMID- 29054212
TI  - Invited Commentary.

PMID- 29054213
TI  - Invited Commentary.

PMID- 29054214
TI  - Robotic-Assisted, Video-Assisted Thoracoscopic and Open Lobectomy: Propensity
      Matched Analysis of Recent Premier Data.
AB  - BACKGROUND: Robotic-assisted lobectomy (RL) is becoming a popular alternative
      technique to video-assisted thoracoscopic lobectomy (VL), although open lobectomy
      (OL) remains the most common approach. The objective of this study is to provide
      a comparative analysis of perioperative clinical outcomes from elective RL, VL,
      and OL. METHODS: The Premier Healthcare Database was analyzed for lobectomies
      performed from January 1, 2011, to September 30, 2015. International
      Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and
      procedure codes were used to identify surgical approaches, complications, and
      mortality. Propensity score matching (1:1) for patient and hospital
      characteristics allowed comparison of RL versus OL (n = 2,775 each) and RL versus
      VL (n = 2,951 each). RESULTS: Compared with OL in propensity matched analysis, RL
      was associated with a lower postoperative complication rate (p < 0.0001), shorter
      hospital stay (p < 0.0001), and lower mortality rate (p = 0.0282). Patients in
      the RL group were more likely to be discharged home than to a transitional health
      care facility (p < 0.0001). Compared with VL, the RL group had a lower conversion
      rate to thoracotomy (p < 0.0001), lower overall postoperative complication rate
      (p = 0.0061), and shorter hospital stay (p = 0.006). The RL patients also were
      more likely to be discharged home than to a transitional health care facility (p
      = 0.0108). The postoperative mortality rates of RL and VL were similar (p =
      0.44). There was no difference in iatrogenic injuries when comparing RL with OL
      and RL with VL (p = 0.1284 and p = 0.5477, respectively). CONCLUSIONS: Robotic
      assisted lobectomy was associated with improved outcomes for certain
      perioperative clinical variables, including shorter length of stay and lower
      complication rates. It was also was associated with a lower conversion rate to OL
      compared with VL.

PMID- 29054215
TI  - Reply.

PMID- 29054216
TI  - Reply.

PMID- 29054217
TI  - Should Immediate Postoperative Oral Nutrition Following Esophagectomy Be
      Generalized Immediately?

PMID- 29054218
TI  - Validity of a Score Created to Predict the Risk of Readmission After Adult
      Cardiac Operations.

PMID- 29054219
TI  - Reply.

PMID- 29054220
TI  - Reply.

PMID- 29054221
TI  - What Treatments Are Needed After Confirming Spontaneous Echo Contrast During
      ECMO?

PMID- 29054222
TI  - The Nuss Procedure After Prior Cardiac Surgery: Friend or Foe?

PMID- 29054223
TI  - Reply.

PMID- 29054224
TI  - Video-Assisted Thoracoscopic Lobectomy for Lung Cancer.

PMID- 29054225
TI  - Improved Closure Technique for Uniportal Video-Assisted Thoracic Surgery: Double
      Embedding Stitching Method.

PMID- 29054226
TI  - Pacemaker Implantation Rate Post Sutureless Aortic Valve Replacement: 23% Is Just
      Too High.

PMID- 29054228
TI  - Novel Airway and Ventilator Management of Tracheobronchial Disruption After Blunt
      Trauma.
AB  - Tracheobronchial injuries can be difficult to diagnose and manage, especially in
      the presence of polytrauma. A 50-year-old woman presented as a Level I trauma
      activation after being struck by a motor vehicle. Initial evaluation demonstrated
      intracranial hemorrhage and multiple chest injuries, including multilevel
      bilateral rib fractures, pneumomediastinum, and concern for tracheobronchial
      injury. After initial stabilization, bronchoscopy was performed and demonstrated
      an injury to the carina. We report a novel airway and ventilation strategy in the
      setting of concomitant tracheobronchial injury after severe blunt chest trauma in
      which extracorporeal support is contraindicated.

PMID- 29054227
TI  - Life-Threatening Cardiac Perforation After Posterior Spondylodesis.
AB  - This reports presents a case of a 62-year-old woman with hemorrhagic hypovolemic
      shock, respiratory distress, and pericardial effusion secondary to right atrial
      perforation caused by a cement embolus after dorsal spondylodesis. Despite
      optimal intensive care support for a supposed pulmonary embolism, the patient's
      condition markedly deteriorated. On delayed embolus recognition by contrast
      enhanced computed tomography and transesophageal echocardiography, she had to
      undergo cardiac surgery. Cardiac involvement is a rare but important
      complication, with few cases described after vertebroplasty and none after
      spondylodesis. In our case, diagnosis before perforation would have allowed an
      endovascular approach, thereby avoiding open heart surgery.

PMID- 29054229
TI  - Complications of Endobronchial Ultrasound-Guided Transbronchial Needle
      Aspiration.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is
      considered useful for the staging and diagnosis of lung cancer or thoracic lymph
      node enlargement; however, little is known about its complications. Between July
      2009 and November 2016, 413 patients underwent EBUS-TBNA, and four complications
      (0.97%) occurred. Here we report four cases involving complications of EBUS-TBNA,
      including mediastinitis (n = 2), obstructive pneumonia (n = 1), and airway
      obstruction requiring admission to the intensive care unit (n = 1). All patients
      recovered with appropriate medical treatment. Despite their low incidence, the
      complications associated with EBUS-TBNA can be serious.

PMID- 29054230
TI  - Near Complete Obliteration of the Left Hemithorax by Congenital Lobar Emphysema
      in an Adult.
AB  - Congenital lobar emphysema is a rare pulmonary malformation typically diagnosed
      during infancy and is characterized by bullous disease. A 28-year-old woman, who
      presented with 1 week of progressive dyspnea and chest pain, was found to have
      left hemithoracic lung hyperinflation with perfusion deficit upon radiographic
      evaluation. Bullous disease was found intraoperatively to originate from 1 lower
      lobe segment. Normal parenchymal lung expansion occurred following resection of
      the affected segment. Therefore, we present a rare case of congenital lobar
      emphysema resulting in near-complete occupancy of the left hemithorax and
      diagnosed in a previously asymptomatic adult without history of predisposing
      factors.

PMID- 29054231
TI  - Lung Procurement After Cardiac Death in a Donor With Previous Median Sternotomy.
AB  - The shortage of lungs for organ donation is problematic, and meeting the demand
      by expanding the donor pool in lung transplantation is critical. Donation after
      cardiac death (DCD) is an under-used approach that could be a valuable source of
      organs. However, procuring lungs from donors with a previous median sternotomy is
      technically difficult and is usually avoided. Here, we describe the procurement
      of lungs from a DCD patient with a previous median sternotomy.

PMID- 29054232
TI  - Surgical Repair of Bland-White-Garland Syndrome With Giant Right Coronary Artery
      Aneurysm.
AB  - A 61-year-old man was diagnosed with adult-type anomalous left coronary artery
      from pulmonary artery (or Bland-White-Garland syndrome) and a giant right
      coronary artery aneurysm. He underwent a thorough anatomic correction to excise
      the aneurysm and reconstruct a coronary system of two vessels. The postoperative
      period of this patient was uneventful.

PMID- 29054233
TI  - Managing a Mycotic Thoracoabdominal Aneurysm: The Importance of Molecular
      Diagnostics.
AB  - Pneumococcal mycotic aneurysms are rare and associated with significant mortality
      and morbidity. Early intravenous antibiotic therapy and surgical intervention is
      the mainstay of treatment. Pneumococci frequently autolyze in blood cultures,
      making microbiological diagnosis challenging. We present the case of a man in his
      mid 70s with multiple thoracoabdominal mycotic aneurysms. Surgery was performed
      to a threatening saccular aortic arch aneurysm. Samples were sent for
      microbiological analysis and all were culture negative. The samples were then
      referred for bacterial 16S ribosomal RNA sequencing, which revealed evidence of
      infection with Streptococcus pneumoniae.

PMID- 29054234
TI  - Coronary Dissection Discovered During Ex Vivo Organ Preservation: Avoiding a
      Fatal Complication.
AB  - This report describes the case of undiagnosed posttraumatic coronary artery
      dissection in a young multiorgan donor. Ex vivo preservation with the Organ Care
      System (TransMedics, Inc, Andover, MA) revealed the presence of coronary disease
      and avoided transplantation of an organ at high risk for failure.

PMID- 29054235
TI  - Acquired Cor Triatriatum Sinister After the Fontan Operation and Successful
      Resection in a Child.
AB  - Cor triatriatum sinister is a rare congenital lesion encountered in children. It
      consists of a fibromuscular membrane that separates the left atrium into two
      chambers resulting in a triatrial heart and often occurs with other structural
      cardiac anomalies. The acquired form is uncommon and has only been reported after
      orthotopic heart transplantation or as a complication of infective endocarditis
      in adults. These cases were mostly because of hypertrophied atrial tissue or
      suture lines and torsion of the atrium. We describe the first case of acquired
      cor triatriatum late after the Fontan procedure with successful surgical
      resection in a child.

PMID- 29054236
TI  - Yasui Conversion for Repair After Left Ventricular Outflow Tract Obstruction.
AB  - We herein report two cases of progressive left ventricular outflow obstruction
      after primary repair of arch obstruction and ventricular septal defect that was
      successfully resolved with Yasui conversion. Patients who require surgical
      reintervention for progressive left ventricular outflow tract (LVOT) obstruction
      after primary biventricular repair of interruption of the aortic arch or
      coarctation of the aorta complex are occasionally experienced. The modified Konno
      procedure and Ross operation are well recognized as useful for these cases.
      However, in some patients, these procedures are difficult to perform because of
      anatomic restrictions or previous procedures. Although the indications are
      limited, the Yasui conversion is a safe, simple, and useful option for LVOT
      obstruction after primary biventricular repair.

PMID- 29054237
TI  - Systemic Venous Rerouting Through the Coronary Sinus for ccTGA With Bilateral
      SVCs.
AB  - The double-switch operation for congenitally corrected transposition of the great
      arteries, in which the morphologic left ventricle is restored to the systemic
      circulation, is an effective surgical option. This case report describes an
      atrial switch technique without using supplemental material during the double
      switch operation for congenitally corrected transposition of the great arteries
      associated with persistent left superior vena cava, with the systemic venous
      blood flow rerouted through the enlarged coronary sinus.

PMID- 29054238
TI  - Effusive Tuberculous Pericarditis.

PMID- 29054239
TI  - Stapler-Based Thoracoscopic Basilar Segmentectomy.
AB  - Thoracoscopic S9-10 segmentectomy is more difficult than other segmentectomies
      because of the complexity of the peripheral pulmonary anatomies and the
      difficulty of dividing the intersegmental plane. In S9-10 segmentectomy, the
      intersegmental plane between segments S6 and S8 near the major fissure impedes
      division of the plane between segments S6 and S9-10, or S8 and S9-10. Dividing
      the intersegmental plane between segments S6 and S8 with stapling is difficult,
      because peripheral pulmonary anatomies are not exposed clearly. Herein, we
      describe the technique of stapler-based thoracoscopic S9-10 segmentectomy under
      indocyanine green fluorescence navigation.

PMID- 29054240
TI  - Thoracoscopic Medial-Basal Segment Segmentectomy.
AB  - The technical details and anatomic features of medial-basal segment (S7)
      segmentectomy have not been reported. We report here thoracoscopic S7
      segmentectomy and S7a subsegmentectomy and explain the anatomic knowledge
      necessary to perform S7 segmentectomy, especially the importance of recognizing
      bronchus (B7) branching patterns before surgery.

PMID- 29054241
TI  - Thoracoscopic Subsuperior Segment Segmentectomy.
AB  - To date, anatomic subsuperior segment (S*) segmentectomy has not yet been
      reported. Herein we report the technical details of thoracoscopic anatomic S*
      segmentectomy and the anatomic features of the S*.

PMID- 29054242
TI  - Pulmonary Vein Widening Plasty for Pulmonary Vein Stenosis and Occlusion After
      Catheter Ablation.
AB  - We successfully performed a pulmonary vein widening plasty in a patient with
      pulmonary vein stenosis and occlusion after multiple catheter ablations for
      paroxysmal atrial fibrillation.

PMID- 29054243
TI  - HIV Testing at Visits to Physicians' Offices in the U.S., 2009-2012.
AB  - INTRODUCTION: HIV testing serves as an entry point for HIV care services for
      those who test HIV positive, and prevention services for those who test HIV
      negative. The Centers for Disease Control and Prevention recommends routine
      testing of adults and adolescents in healthcare settings. To identify missed
      opportunities for HIV testing at U.S. physicians' offices, data from the National
      Ambulatory Care Surveys from 2009 to 2012 were analyzed. METHODS: The mean annual
      number and percentage of visits with an HIV test among HIV-uninfected nonpregnant
      females and males aged 15-65 years was estimated using weighted survey data.
      Factors associated with HIV testing at visits to physicians' offices were
      identified. RESULTS: The mean annual number of U.S. physicians' office visits
      with an HIV test conducted was 1,396,736 (0.4% of all visits) among nonpregnant
      females and 986,891 (0.5% of all visits) among males. For both nonpregnant
      females and males, HIV testing prevalence was highest among those aged 20-29
      years (1.3% of all visits by nonpregnant females; 1.7% of all visits by males)
      and non-Hispanic blacks (1.1% of all visits by nonpregnant females; 1.0% of all
      visits by males). An HIV test was not conducted at 98.5% of visits at which
      venipuncture was performed for both nonpregnant females and males. CONCLUSIONS:
      Important opportunities exist to increase HIV testing coverage at U.S.
      physicians' offices. Structural interventions, such as routine opt-out testing
      policies, electronic medical record notifications, and use of non-clinical staff
      for testing could be implemented to increase HIV testing in these settings.

PMID- 29054244
TI  - Questions Regarding Study Design and Analysis in "Previous Suicide Attempt and
      its Association With Method Used in a Suicide Death".

PMID- 29054245
TI  - Response to Letter to the Editor: "Questions Regarding Study Design and Analysis
      in 'Previous Suicide Attempt and its Association With Method Used in a Suicide
      Death'".

PMID- 29054246
TI  - Increased Use of BRCA Mutation Test in Unaffected Women Over the Period 2004-2014
      in the U.S.: Further Evidence of the "Angelina Jolie Effect"?

PMID- 29054247
TI  - Authors' Response: "Angelina Jolie Effect" on the Shifting Role of BRCA Testing
      in the U.S.

PMID- 29054248
TI  - Corrigendum to "Evaluation of a Salmonella Enteritidis vaccine and related ELISA
      for respective induction and assessment of acquired immunity to the vaccine
      and/or Echinacea purpurea in Awassi Ewes" [Vaccine 33 (2015) 2228-2231].

PMID- 29054249
TI  - HIV-1-infected T-cells dynamics and prognosis: An evolutionary game model.
AB  - BACKGROUND AND OBJECTIVE: Understanding the dynamics of human immunodeficiency
      virus (HIV) is essential for depicting, developing, and investigating effective
      treatment strategies. HIV infects several types of immune cells, but its main
      target is to destroy helper T-cells. In the lymph nodes, the infected T-cells
      interact with each other and their environment to obtain more resources.
      According to infectivity and replicative capacity of T-cells in the HIV infection
      process, they can be divided into four phenotypes. Although genetic mutations in
      the reverse transcription that beget these phenotypes are random, the framework
      by which a phenotype become favored is affected by the environment and
      neighboring phenotypes. Moreover, the HIV disease has all components of an
      evolutionary process, including replication, mutation, and selection. METHODS: We
      propose a novel structure-based game-theoretic model for the evolution of HIV-1
      Infected CD4+T-cells and invasion of the immune system. We discuss the
      theoretical basis of the stable equilibrium states of the evolutionary dynamics
      of four T-cells types as well as its significant results to understand and
      control HIV infection. The results include the importance of genetic variations
      and the process of establishing evolutionary dynamics of the virus quasispecies.
      RESULTS: Our results show that there is a direct dependency between some
      parameters such as mutation rates and the stability of equilibrium states in the
      HIV infection. This is an interesting result because these parameters can be
      changed by some pharmacotherapies and alternative treatments. Our model indicates
      that in an appropriate treatment the relative frequency of the wild type of virus
      quasispecies can be decreased in the population. Consequently, this can cause
      delaying the emergence of the AIDS phase. To assess the model, we investigate two
      new treatments for HIV. The results show that our model can predict the treatment
      results. CONCLUSIONS: The paper shows that a structured-based evolutionary game
      theory can model the evolutionary dynamics of the infected T-cells and virus
      quasispecies. The model predicts certain aspects of the HIV infection process
      under several treatments.

PMID- 29054250
TI  - Using anchors from free text in electronic health records to diagnose
      postoperative delirium.
AB  - OBJECTIVES: Postoperative delirium is a common complication after major surgery
      among the elderly. Despite its potentially serious consequences, the complication
      often goes undetected and undiagnosed. In order to provide diagnosis support one
      could potentially exploit the information hidden in free text documents from
      electronic health records using data-driven clinical decision support tools.
      However, these tools depend on labeled training data and can be both time
      consuming and expensive to create. METHODS: The recent learning with anchors
      framework resolves this problem by transforming key observations (anchors) into
      labels. This is a promising framework, but it is heavily reliant on clinicians
      knowledge for specifying good anchor choices in order to perform well. In this
      paper we propose a novel method for specifying anchors from free text documents,
      following an exploratory data analysis approach based on clustering and data
      visualization techniques. We investigate the use of the new framework as a way to
      detect postoperative delirium. RESULTS: By applying the proposed method to
      medical data gathered from a Norwegian university hospital, we increase the area
      under the precision-recall curve from 0.51 to 0.96 compared to baselines.
      CONCLUSIONS: The proposed approach can be used as a framework for clinical
      decision support for postoperative delirium.

PMID- 29054251
TI  - A segmentation method based on HMRF for the aided diagnosis of acute myeloid
      leukemia.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis of acute myeloid leukemia (AML) is
      purely dependent on counting the percentages of blasts (>20%) in the peripheral
      blood or bone marrow. Manual microscopic examination of peripheral blood or bone
      marrow aspirate smears is time consuming and less accurate. The first and very
      important step in blast recognition is the segmentation of the cells from the
      background for further cell feature extraction and cell classification. In this
      paper, we aimed to utilize computer technologies in image analysis and artificial
      intelligence to develop an automatic program for blast recognition and counting
      in the aspirate smears. METHODS: We proposed a method to analyze the aspirate
      smear images, which first performs segmentation of the cells by k-means cluster,
      then builds cell image representing model by HMRF (Hidden-Markov Random Field),
      estimates model parameters through probability of EM (expectation maximization),
      carries out convergence iteration until optimal value, and finally achieves
      second stage refined segmentation. Furthermore, the segmentation results are
      compared with several other methods using six classes of cells respectively.
      RESULTS: The proposed method was applied to six groups of cells from 61 bone
      marrow aspirate images, and compared with other algorithms for its performance on
      the analysis of the whole images, the segmentation of nucleus, and the efficiency
      of calculation. It showed improved segmentation results in both the cropped
      images and the whole images, which provide the base for down-stream cell feature
      extraction and identification. CONCLUSIONS: Segmentation of the aspirate smear
      images using the proposed method helps the analyst in differentiating six groups
      of cells and in the determination of blasts counting, which will be of great
      significance for the diagnosis of acute myeloid leukemia.

PMID- 29054252
TI  - Methodology on quantification of sonication duration for safe application of MR
      guided focused ultrasound for liver tumour ablation.
AB  - BACKGROUND AND OBJECTIVE: Magnetic Resonance Guided Focused Ultrasound (MRgFUS)
      for liver tumour ablation is a challenging task due to motion caused by breathing
      and occlusion due the ribcage between the transducer and the tumour. To overcome
      these challenges, a novel system for liver tumour ablation during free breathing
      has been designed. METHODS: The novel TRANS-FUSIMO Treatment System (TTS, EUFP7)
      interacts with a Magnetic Resonance (MR) scanner and a focused ultrasound
      transducer to sonicate to a moving target in liver. To meet the requirements of
      ISO 13485; a quality management system for medical device design, the system
      needs to be tested for certain process parameters. The duration of sonication
      and, the delay after the sonication button is activated, are among the parameters
      that need to be quantified for efficient and safe ablation of tumour tissue. A
      novel methodology is developed to quantify these process parameters. A
      computerised scope is programmed in LabVIEW to collect data via hydrophone; where
      the coordinates of fiber-optic sensor assembly was fed into the TRANS-FUSIMO
      treatment software via Magnetic Resonance Imaging (MRI) to sonicate to the tip of
      the sensor, which is synchronised with the clock of the scope, embedded in a
      degassed water tank via sensor assembly holder. The sonications were executed for
      50 W, 100 W, 150 W for 10 s to quantify the actual sonication duration and the
      delay after the emergency stop by two independent operators for thirty times. The
      deviation of the system from the predefined specs was calculated. Student's-T
      test was used to investigate the user dependency. RESULTS: The duration of
      sonication and the delay after the sonication were quantified successfully with
      the developed method. TTS can sonicate with a maximum deviation of 0.16 s (Std
      0.32) from the planned duration and with a delay of 14 ms (Std 0.14) for the
      emergency stop. Student's T tests indicate that the results do not depend on
      operators (p > .05). CONCLUSION: The evidence obtained via this protocol is
      crucial for translation- of-research into the clinics for safe application of
      MRgFUS. The developed protocol could be used for system maintenance in compliance
      with quality systems in clinics for daily quality assurance routines.

PMID- 29054253
TI  - Binary classification of multichannel-EEG records based on the epsilon-complexity
      of continuous vector functions.
AB  - BACKGROUND AND OBJECTIVE: A crucial step in a classification of
      electroencephalogram (EEG) records is the feature selection. The feature
      selection problem is difficult because of the complex structure of EEG signals.
      To classify the EEG signals with good accuracy, most of the recently published
      studies have used high-dimensional feature spaces. Our objective is to create a
      low-dimensional feature space that enables binary classification of EEG records.
      METHODS: The proposed approach is based on our theory of the epsilon-complexity
      of continuous functions, which is extended here (see Appendix) to the case of
      vector functions. This extension permits us to handle multichannel-EEG records.
      The method consists of two steps. Firstly, we estimate the epsilon-complexity
      coefficients of the original signal and its finite differences. Secondly, we
      utilize the random forest (RF) or support vector machine (SVM) classifier.
      RESULTS: We demonstrated the performance of our method on simulated data. We also
      applied it to the problem of classification of multichannel-EEG records related
      to a group of healthy adolescents (39 subjects) and a group of adolescents with
      schizophrenia (45 subjects). We found that the random forest classifier provides
      a superior result. In particular, out-of-bag accuracy in the case of RF was
      85.3%. Using 10-fold cross-validation (CV), RF gave an average accuracy of 84.5%
      on a test set, whereas SVM gave an accuracy of 81.07%. We note that the highest
      accuracy on CV was 89.3%. To compare our method with the classical approach, we
      performed classification using the spectral features. In this case, the best
      performance was achieved using seven-dimensional feature space, with an average
      accuracy of 83.6%. CONCLUSIONS: We developed a model-free method for binary
      classification of EEG records. The feature space was reduced to four dimensions.
      The results obtained indicate the effectiveness of the proposed method.

PMID- 29054254
TI  - ECG based Myocardial Infarction detection using Hybrid Firefly Algorithm.
AB  - BACKGROUND AND OBJECTIVE: Myocardial Infarction (MI) is one of the most frequent
      diseases, and can also cause demise, disability and monetary loss in patients who
      suffer from cardiovascular disorder. Diagnostic methods of this ailment by
      physicians are typically invasive, even though they do not fulfill the required
      detection accuracy. METHODS: Recent feature extraction methods, for example, Auto
      Regressive (AR) modelling; Magnitude Squared Coherence (MSC); Wavelet Coherence
      (WTC) using Physionet database, yielded a collection of huge feature set. A large
      number of these features may be inconsequential containing some excess and non
      discriminative components that present excess burden in computation and loss of
      execution performance. So Hybrid Firefly and Particle Swarm Optimization (FFPSO)
      is directly used to optimise the raw ECG signal instead of extracting features
      using the above feature extraction techniques. RESULTS: Provided results in this
      paper show that, for the detection of MI class, the FFPSO algorithm with ANN
      gives 99.3% accuracy, sensitivity of 99.97%, and specificity of 98.7% on MIT-BIH
      database by including NSR database also. CONCLUSIONS: The proposed approach has
      shown that methods that are based on the feature optimization of the ECG signals
      are the perfect to diagnosis the condition of the heart patients.

PMID- 29054255
TI  - Predicting CD4 count changes among patients on antiretroviral treatment:
      Application of data mining techniques.
AB  - BACKGROUND AND OBJECTIVES: To monitor the progress of therapy and disease
      progression, periodic CD4 counts are required throughout the course of HIV/AIDS
      care and support. The demand for CD4 count measurement is increasing as ART
      programs expand over the last decade. This study aimed to predict CD4 count
      changes and to identify the predictors of CD4 count changes among patients on
      ART. METHODS: A cross-sectional study was conducted at the University of Gondar
      Hospital from 3,104 adult patients on ART with CD4 counts measured at least twice
      (baseline and most recent). Data were retrieved from the HIV care clinic
      electronic database and patients' charts. Descriptive data were analyzed by SPSS
      version 20. Cross-Industry Standard Process for Data Mining (CRISP-DM)
      methodology was followed to undertake the study. WEKA version 3.8 was used to
      conduct a predictive data mining. Before building the predictive data mining
      models, information gain values and correlation-based Feature Selection methods
      were used for attribute selection. Variables were ranked according to their
      relevance based on their information gain values. J48, Neural Network, and Random
      Forest algorithms were experimented to assess model accuracies. RESULT: The
      median duration of ART was 191.5 weeks. The mean CD4 count change was 243 (SD
      191.14) cells per microliter. Overall, 2427 (78.2%) patients had their CD4 counts
      increased by at least 100 cells per microliter, while 4% had a decline from the
      baseline CD4 value. Baseline variables including age, educational status, CD8
      count, ART regimen, and hemoglobin levels predicted CD4 count changes with
      predictive accuracies of J48, Neural Network, and Random Forest being 87.1%,
      83.5%, and 99.8%, respectively. Random Forest algorithm had a superior
      performance accuracy level than both J48 and Artificial Neural Network. The
      precision, sensitivity and recall values of Random Forest were also more than
      99%. CONCLUSIONS: Nearly accurate prediction results were obtained using Random
      Forest algorithm. This algorithm could be used in a low-resource setting to build
      a web-based prediction model for CD4 count changes.

PMID- 29054256
TI  - Drug-target interaction prediction: A Bayesian ranking approach.
AB  - BACKGROUND AND OBJECTIVE: In silico prediction of drug-target interactions (DTI)
      could provide valuable information and speed-up the process of drug repositioning
      - finding novel usage for existing drugs. In our work, we focus on machine
      learning algorithms supporting drug-centric repositioning approach, which aims to
      find novel usage for existing or abandoned drugs. We aim at proposing a per-drug
      ranking-based method, which reflects the needs of drug-centric repositioning
      research better than conventional drug-target prediction approaches. METHODS: We
      propose Bayesian Ranking Prediction of Drug-Target Interactions (BRDTI). The
      method is based on Bayesian Personalized Ranking matrix factorization (BPR) which
      has been shown to be an excellent approach for various preference learning tasks,
      however, it has not been used for DTI prediction previously. In order to
      successfully deal with DTI challenges, we extended BPR by proposing: (i) the
      incorporation of target bias, (ii) a technique to handle new drugs and (iii)
      content alignment to take structural similarities of drugs and targets into
      account. RESULTS: Evaluation on five benchmark datasets shows that BRDTI
      outperforms several state-of-the-art approaches in terms of per-drug nDCG and
      AUC. BRDTI results w.r.t. nDCG are 0.929, 0.953, 0.948, 0.897 and 0.690 for G
      Protein Coupled Receptors (GPCR), Ion Channels (IC), Nuclear Receptors (NR),
      Enzymes (E) and Kinase (K) datasets respectively. Additionally, BRDTI
      significantly outperformed other methods (BLM-NII, WNN-GIP, NetLapRLS and CMF)
      w.r.t. nDCG in 17 out of 20 cases. Furthermore, BRDTI was also shown to be able
      to predict novel drug-target interactions not contained in the original datasets.
      The average recall at top-10 predicted targets for each drug was 0.762, 0.560,
      1.000 and 0.404 for GPCR, IC, NR, and E datasets respectively. CONCLUSIONS: Based
      on the evaluation, we can conclude that BRDTI is an appropriate choice for
      researchers looking for an in silico DTI prediction technique to be used in drug
      centric repositioning scenarios. BRDTI Software and supplementary materials are
      available online at www.ksi.mff.cuni.cz/~peska/BRDTI.

PMID- 29054257
TI  - Theoretical prediction of pullout strengths for dental and orthopaedic screws
      with conical profile and buttress threads.
AB  - BACKGROUND AND OBJECTIVE: The pullout strength of a screw is an indicator of how
      secure bone fragments are being held in place. Such bone-purchasing ability is
      sensitive to bone quality, thread design, and the pilot hole, and is often
      evaluated by experimental and numerical methods. Historically, there are some
      mathematical formulae to simulate the screw withdrawal from the synthetic bone.
      There are great variations in screw specifications. However, extensive
      investigation of the correlation between experimental and analytical results has
      not been reported in literature. METHODS: Referring to the literature formulae,
      this study aims to evaluate the differences in the calculated pullout strengths.
      The pullout tests of the surgical screws are measured and the sawbone is used as
      the testing block. The absolute errors and correlation coefficients of the
      experimental and analytical results are calculated as the comparison baselines of
      the formulae. RESULTS: The absolute error of the dental, traumatic, and spinal
      groups are 21.7%, 95.5%, and 37.0%, respectively. For the screws with a conical
      profile and/or tiny threads, the calculated and measured results are not well
      correlated. The formulae are not accurate indicators of the pullout strengths of
      the screws where the design parameters are slightly varied. However, the
      experimental and numerical results are highly correlated for the cylindrical
      screws. The pullout strength of a conical screw is higher than that of its
      counterpart, but all formulae consistently predict the opposite results. In
      general, the bony purchase of the buttress threads is securer than that of the
      symmetric thread. CONCLUSIONS: An absolute error of up to 51.4% indicates the
      theoretical results cannot predict the actual value of the pullout strength. Only
      thread diameter, pitch, and depth are considered in the investigated formulae.
      The thread profile and shape should be formulated to modify the slippage
      mechanism at the bone-screw interfaces and simulate the strength change in the
      squeezed bones, especially for the conical screw.

PMID- 29054258
TI  - Comparative approaches for classification of diabetes mellitus data: Machine
      learning paradigm.
AB  - BACKGROUND AND OBJECTIVE: Diabetes is a silent killer. The main cause of this
      disease is the presence of excessive amounts of metabolites such as glucose.
      There were about 387 million diabetic people all over the world in 2014. The
      financial burden of this disease has been calculated to be about $13,700 per
      year. According to the World Health Organization (WHO), these figures will more
      than double by the year 2030. This cost will be reduced dramatically if someone
      can predict diabetes statistically on the basis of some covariates. Although
      several classification techniques are available, it is very difficult to classify
      diabetes. The main objectives of this paper are as follows: (i) Gaussian process
      classification (GPC), (ii) comparative classifier for diabetes data
      classification, (iii) data analysis using the cross-validation approach, (iv)
      interpretation of the data analysis and (v) benchmarking our method against
      others. METHODS: To classify diabetes, several classification techniques are used
      such as linear discriminant analysis (LDA), quadratic discriminant analysis
      (QDA), and Naive Bayes (NB). However, most of the medical data show non
      normality, non-linearity and inherent correlation structure. So in this paper we
      adapted Gaussian process (GP)-based classification technique using three kernels
      namely: linear, polynomial and radial basis kernel. We also investigate the
      performance of a GP-based classification technique in comparison to existing
      techniques such as LDA, QDA and NB. Performances are evaluated by using the
      accuracy (ACC), sensitivity (SE), specificity (SP), positive predictive value
      (PPV), negative predictive value (NPV) and receiver-operating characteristic
      (ROC) curves. RESULTS: Pima Indian diabetes dataset is taken as part of the
      study. This consists of 768 patients, of which 268 patients are diabetic and 500
      patients are controls. Our machine learning system shows the performance of GP
      based model as: ACC 81.97%, SE 91.79%, SP 63.33%, PPV 84.91% and NPV 62.50% which
      are larger compared to other methods.

PMID- 29054259
TI  - Enhancing performance of P300-Speller under mental workload by incorporating dual
      task data during classifier training.
AB  - As one of the most important brain-computer interface (BCI) paradigms, P300
      Speller was shown to be significantly impaired once applied in practical
      situations due to effects of mental workload. This study aims to provide a new
      method of building training models to enhance performance of P300-Speller under
      mental workload. Three experiment conditions based on row-column P300-Speller
      paradigm were performed including speller-only, 3-back-speller and mental
      arithmetic-speller. Data under dual-task conditions were introduced to speller
      only data respectively to build new training models. Then performance of
      classifiers with different models was compared under the same testing condition.
      The results showed that when tasks of imported training data and testing data
      were the same, character recognition accuracies and round accuracies of P300
      Speller with mixed-data training models significantly improved (FDR, p < 0.005).
      When they were different, performance significantly improved when tested on
      mental-arithmetic-speller (FDR, p < 0.05) while the improvement was modest when
      tested on n-back-speller (FDR, p < 0.1). The analysis of ERPs revealed that ERP
      difference between training data and testing data was significantly diminished
      when the dual-task data was introduced to training data (FDR, p < 0.05). The new
      method of training classifier on mixed data proved to be effective in enhancing
      performance of P300-Speller under mental workload, confirmed the feasibility to
      build a universal training model and overcome the effects of mental workload in
      its practical applications.

PMID- 29054260
TI  - Edge enhancement algorithm for low-dose X-ray fluoroscopic imaging.
AB  - BACKGROUND AND OBJECTIVE: Low-dose X-ray fluoroscopy has continually evolved to
      reduce radiation risk to patients during clinical diagnosis and surgery. However,
      the reduction in dose exposure causes quality degradation of the acquired images.
      In general, an X-ray device has a time-average pre-processor to remove the
      generated quantum noise. However, this pre-processor causes blurring and
      artifacts within the moving edge regions, and noise remains in the image. During
      high-pass filtering (HPF) to enhance edge detail, this noise in the image is
      amplified. METHODS: In this study, a 2D edge enhancement algorithm comprising
      region adaptive HPF with the transient improvement (TI) method, as well as
      artifacts and noise reduction (ANR), was developed for degraded X-ray
      fluoroscopic images. The proposed method was applied in a static scene pre
      processed by a low-dose X-ray fluoroscopy device. First, the sharpness of the X
      ray image was improved using region adaptive HPF with the TI method, which
      facilitates sharpening of edge details without overshoot problems. Then, an ANR
      filter that uses an edge directional kernel was developed to remove the artifacts
      and noise that can occur during sharpening, while preserving edge details.
      RESULTS: The quantitative and qualitative results obtained by applying the
      developed method to low-dose X-ray fluoroscopic images and visually and
      numerically comparing the final images with images improved using conventional
      edge enhancement techniques indicate that the proposed method outperforms
      existing edge enhancement methods in terms of objective criteria and subjective
      visual perception of the actual X-ray fluoroscopic image. CONCLUSIONS: The
      developed edge enhancement algorithm performed well when applied to actual low
      dose X-ray fluoroscopic images, not only by improving the sharpness, but also by
      removing artifacts and noise, including overshoot.

PMID- 29054261
TI  - Development and validation of various phenotyping algorithms for Diabetes
      Mellitus using data from electronic health records.
AB  - BACKGROUND AND OBJECTIVE: Recent progression towards precision medicine has
      encouraged the use of electronic health records (EHRs) as a source for large
      amounts of data, which is required for studying the effect of treatments or risk
      factors in more specific subpopulations. Phenotyping algorithms allow to
      automatically classify patients according to their particular electronic
      phenotype thus facilitating the setup of retrospective cohorts. Our objective is
      to compare the performance of different classification strategies (only using
      standardized problems, rule-based algorithms, statistical learning algorithms
      (six learners) and stacked generalization (five versions)), for the
      categorization of patients according to their diabetic status (diabetics, not
      diabetics and inconclusive; Diabetes of any type) using information extracted
      from EHRs. METHODS: Patient information was extracted from the EHR at Hospital
      Italiano de Buenos Aires, Buenos Aires, Argentina. For the derivation and
      validation datasets, two probabilistic samples of patients from different years
      (2005: n = 1663; 2015: n = 800) were extracted. The only inclusion criterion was
      age (>=40 & <80 years). Four researchers manually reviewed all records and
      classified patients according to their diabetic status (diabetic: diabetes
      registered as a health problem or fulfilling the ADA criteria; non-diabetic: not
      fulfilling the ADA criteria and having at least one fasting glycemia below 126
      mg/dL; inconclusive: no data regarding their diabetic status or only one abnormal
      value). The best performing algorithms within each strategy were tested on the
      validation set. RESULTS: The standardized codes algorithm achieved a Kappa
      coefficient value of 0.59 (95% CI 0.49, 0.59) in the validation set. The Boolean
      logic algorithm reached 0.82 (95% CI 0.76, 0.88). A slightly higher value was
      achieved by the Feedforward Neural Network (0.9, 95% CI 0.85, 0.94). The best
      performing learner was the stacked generalization meta-learner that reached a
      Kappa coefficient value of 0.95 (95% CI 0.91, 0.98). CONCLUSIONS: The stacked
      generalization strategy and the feedforward neural network showed the best
      classification metrics in the validation set. The implementation of these
      algorithms enables the exploitation of the data of thousands of patients
      accurately.

PMID- 29054262
TI  - Evaluation of robotic surgery skills using dynamic time warping.
AB  - BACKGROUND AND OBJECTIVE: accompanied with the wide acceptance of robot assisted
      minimally invasive surgery (RMIS), the demand for efficient and objective
      surgical skills evaluation method is increased. Recently, with the development of
      medical engineering technology, several evaluation methods have been proposed.
      Among them, kinematic analysis, an unsupervised and data-based method, has been
      accepted by many researchers. However, this method is still limited by the number
      of metrics and unconvinced scoring system. This paper aims to propose a new
      evaluation method to assess surgical skills efficiently and objectively. METHODS:
      this research proposed an efficient and effective surgical skills evaluation
      algorithm which used the trajectories of instrument tip and dynamic time warping
      (DTW) to provide trainees with real-time and summative feedback. The optimum
      trajectories based on 'Therbligs' theory was designed as a template. DTW
      algorithm was used to align actual trajectories to optimum trajectories with an
      evaluating indicator designed to emphasize the crucial motion features in
      surgical skills evaluation. The real-time feedback was obtained through a sliding
      time window to help trainees improve learning efficiency. RESULTS: experts (n =
      2) and novices (n = 8) were invited to complete the peg transfer tasks and 60
      instrument tip trajectories were assessed by the proposed algorithm. Significant
      differences between different groups were observed (experts' right trajectories
      versus experts' left trajectories, p = 0.0002; experts' right trajectories versus
      novices' right trajectories, p = 0.0124). In addition, evaluation results of
      trajectories with operational mistakes were significantly different from those of
      others. CONCLUSIONS: the proposed evaluation method showed its advantages in
      distinguishing and evaluating surgical performance. Given its ability to evaluate
      the performance based on kinematic information, the proposed evaluation method
      can be further developed in the future. Furthermore, because the proposed method
      can provide real-time feedback, it also has the potential to be a monitoring
      system in operation room.

PMID- 29054263
TI  - nmsBuilder: Freeware to create subject-specific musculoskeletal models for
      OpenSim.
AB  - BACKGROUND AND OBJECTIVE: Musculoskeletal modeling and simulations of movement
      have been increasingly used in orthopedic and neurological scenarios, with
      increased attention to subject-specific applications. In general, musculoskeletal
      modeling applications have been facilitated by the development of dedicated
      software tools; however, subject-specific studies have been limited also by time
      consuming modeling workflows and high skilled expertise required. In addition, no
      reference tools exist to standardize the process of musculoskeletal model
      creation and make it more efficient. Here we present a freely available software
      application, nmsBuilder 2.0, to create musculoskeletal models in the file format
      of OpenSim, a widely-used open-source platform for musculoskeletal modeling and
      simulation. nmsBuilder 2.0 is the result of a major refactoring of a previous
      implementation that moved a first step toward an efficient workflow for subject
      specific model creation. METHODS: nmsBuilder includes a graphical user interface
      that provides access to all functionalities, based on a framework for computer
      aided medicine written in C++. The operations implemented can be used in a
      workflow to create OpenSim musculoskeletal models from 3D surfaces. A first step
      includes data processing to create supporting objects necessary to create models,
      e.g. surfaces, anatomical landmarks, reference systems; and a second step
      includes the creation of OpenSim objects, e.g. bodies, joints, muscles, and the
      corresponding model. RESULTS: We present a case study using nmsBuilder 2.0: the
      creation of an MRI-based musculoskeletal model of the lower limb. The model
      included four rigid bodies, five degrees of freedom and 43 musculotendon
      actuators, and was created from 3D surfaces of the segmented images of a healthy
      subject through the modeling workflow implemented in the software application.
      CONCLUSIONS: We have presented nmsBuilder 2.0 for the creation of musculoskeletal
      OpenSim models from image-based data, and made it freely available via
      nmsbuilder.org. This application provides an efficient workflow for model
      creation and helps standardize the process. We hope this would help promote
      personalized applications in musculoskeletal biomechanics, including larger
      sample size studies, and might also represent a basis for future developments for
      specific applications.

PMID- 29054264
TI  - Using artificial neural networks to select the parameters for the prognostic of
      mild cognitive impairment and dementia in elderly individuals.
AB  - BACKGROUND AND OBJECTIVES: A huge number of solutions based on computational
      systems have been recently developed for the classification of cognitive
      abnormalities in older people, so that individuals at high risk of developing
      neurodegenerative diseases, such as Cognitive Impairment and Alzheimer?s disease,
      can be identified before the manifestation of the diseases. Several factors are
      related to these pathologies, making the diagnostic process a hard problem to
      solve. This paper proposes a computational model based on the artificial neural
      network to classify data patterns of older adults. METHODS: The proposal takes
      into account the several parameters as diagnostic factors as gender, age, the
      level of education, study time, and scores from cognitive tests (Mini-Mental
      State Examination, Semantic Verbal Fluency Test, Clinical Dementia Rating and
      Ascertaining Dementia). This non-linear regression model is designed to classify
      healthy and pathological aging with machine learning techniques such as neural
      networks, random forest, SVM, and stochastic gradient boosting. We deployed a
      simple linear regression model for the sake of comparison. The primary objective
      is to use a regression model to analyze the data set aiming to check which
      parameters are necessary to achieve high accuracy in the diagnosis of
      neurodegenerative disorders. RESULTS: The analysis demonstrated that the usage of
      cognitive tests produces median values for the accuracy greater than 90%. The ROC
      analysis shows that the best sensitivity performance is above 98% and specificity
      of 96% when the configurations have only cognitive tests. CONCLUSIONS: The
      presented approach is a valuable tool for identifying patients with dementia or
      MCI and for supporting the clinician in the diagnostic process, by providing an
      outstanding support decision tool in the diagnostics of neurodegenerative
      diseases.

PMID- 29054265
TI  - Mining new applications from current algorithms.

PMID- 29054266
TI  - Circulating Peptidome and Tumor-Resident Proteolysis.
AB  - Mammalian proteases segregate into several distinct protein families that employ
      different functional domains to hydrolyze peptides bonds with different
      specificities and affinities. These enzymes play central roles in critical
      cellular and systemic processes, including regulation of cell growth,
      differentiation, homeostasis, and apoptosis; and cancer initiation, progression,
      and metastasis. Human proteases segregate into five distinct catalytic classes;
      the metalloprotease, serine protease, and cysteine protease families have the
      most members, while the aspartic and threonine peptidase families have relatively
      few examples. Section 1 discusses the five different types of human proteases and
      summarizes some of their known functions during tumorigenesis, migration, and
      metastasis. Section 2 focuses on how cancer degradomes, defined as all the
      proteases, protease inhibitors, and protease substrates regulated by a given
      cancer, affect cancer promotion and suppression, and current approaches for
      degradome profiling. Protein degradation products generated during cancer
      progression, invasion, and metastasis alter the tumor microenvironment to
      influence these processes. These cancer-associated protein degradation profiles
      (aka tumor peptidomes) represent a potentially rich pool of candidates for cancer
      biomarker discovery. Section 3 focuses on the benefits and challenges associated
      with peptidome studies, and methods employed to conduct them. Section 4 discusses
      recent studies that use circulating peptides as cancer biomarkers, and how the
      abundance of peptides reflects the activity of their source proteases during
      cancer progression. We hope this chapter will convey a good sense of current
      research on how cancer-associated proteases, degradomes, and their resulting
      peptidomes can improve our knowledge of cancer biology, improve diagnosis and
      evaluation, and inspire new ideas in this and related research areas.

PMID- 29054267
TI  - Strategies for Characterization of Low-Abundant Intact or Truncated Low-Molecular
      Weight Proteins From Human Plasma.
AB  - Low-molecular-weight region (LMW, MW<=30kDa) of human serum/plasma proteins,
      including small intact proteins, truncated fragments of larger proteins, along
      with some other small components, has been associated with the ongoing
      physiological and pathological events, and thereby represent a treasure trove of
      diagnostic molecules. Great progress in the mining of novel biomarkers from this
      diagnostic treasure trove for disease diagnosis and health monitoring has been
      achieved based on serum samples from healthy individuals and patients and
      powerful new approaches in biochemistry and systems biology. However, cumulative
      evidence indicates that many potential LMW protein biomarkers might still have
      escaped from detection due to their low abundance, the dynamic complexity of
      serum/plasma, and the limited efficiency of characterization approaches. Here, we
      provide an overview of the current state of knowledge with respect to strategies
      for the characterization of low-abundant LMW proteins (small intact or truncated
      proteins) from human serum/plasma, involving prefractionation or enrichment
      methods to reduce dynamic range and mass spectrometry-based characterization of
      low-abundant LMW proteins.

PMID- 29054269
TI  - Exploiting Enzyme Alterations in Cancer for Drug Activation, Drug Delivery, and
      Nanotherapy.
AB  - Alterations of enzyme activity or enzyme levels in cancer tissue have been
      documented over the years. Taking advantage of these observations, various
      strategies for drug activation and drug delivery have been developed. One example
      is a mechanism called "prodrugs" that generates active drugs by enzyme cleavage.
      Another example is enzyme-induced anticancer drug release mechanisms. This system
      is constructed by incorporating enzyme-sensitive linkages to materials such as
      hydrogels and nanodelivery vehicles, including liposomes, polymer micelles, and
      mesoporous silica nanoparticles. Various release mechanisms for anticancer drugs
      and siRNA have been developed. In addition, enzyme cleavage is utilized in
      nanodelivery vehicles that contain nanomachines. One example is nanovalve that
      can be opened by enzyme cleavage. Another example is enzyme-induced release of
      nanoparticles from multistage vehicles. Finally, colon-specific drug delivery by
      azoreductase cleavable mechanism is discussed.

PMID- 29054270
TI  - The Peptidome Comes of Age: Mass Spectrometry-Based Characterization of the
      Circulating Cancer Peptidome.
AB  - Peptides play a seminal role in most physiological processes acting as
      neurotransmitters, hormones, antibiotics, and immune regulation. In the context
      of tumor biology, it is hypothesized that endogenous peptides, hormones,
      cytokines, growth factors, and aberrant degradation of select protein networks
      (e.g., enzymatic activities, protein shedding, and extracellular matrix
      remodeling) are fundamental in mediating cancer progression. Analysis of peptides
      in biological fluids by mass spectrometry holds promise of providing sensitive
      and specific diagnostic and prognostic information for cancer and other diseases.
      The identification of circulating peptides in the context of disease constitutes
      a hitherto source of new clinical biomarkers. The field of peptidomics can be
      defined as the identification and comprehensive analysis of physiological and
      pathological peptides. Like proteomics, peptidomics has been advanced by the
      development of new separation strategies, analytical detection methods such as
      mass spectrometry, and bioinformatic technologies. Unlike proteomics, peptidomics
      is targeted toward identifying endogenous protein and peptide fragments, defining
      proteolytic enzyme substrate specificity, as well as protease cleavage
      recognition (degradome). Peptidomics employs "top-down proteomics" strategies
      where mass spectrometry is applied at the proteoform level to analyze intact
      proteins and large endogenous peptide fragments. With recent advances in
      prefractionation workflows for separating peptides, mass spectrometry
      instrumentation, and informatics, peptidomics is an important field that promises
      to impact on translational medicine. This review covers the current advances in
      peptidomics, including top-down and imaging mass spectrometry, comprehensive
      quantitative peptidome analyses (developments in reproducibility and coverage),
      peptide prefractionation and enrichment workflows, peptidomic data analyses, and
      informatic tools. The application of peptidomics in cancer biomarker discovery
      will be discussed.

PMID- 29054271
TI  - Peptide Hormones as Tumor Markers in Clinical Practice.
AB  - Peptide hormones represent a major class of hormones that are made from amino
      acids by specialized endocrine glands. The maturation of bioactive hormones take
      place in the rough endoplasmic reticulum and Golgi apparatus, where
      preprohormones are proteolytically cleaved into prohormones, and subsequently
      into mature peptide hormones. Once the bioactive hormones are released into the
      circulation, they interact with receptors located on the plasma membrane of
      target cells, and initiate intracellular signaling pathways to regulate
      physiological processes including energy metabolism, growth, stress, and
      reproduction. However, excessive amount of circulating peptide hormones often
      associates with the presence of tumors. Section 2 discusses 10 peptide hormones
      as tumor markers and their clinical application in aiding the diagnosis of tumors
      as well as monitoring the disease process.

PMID- 29054268
TI  - Saliva-Exosomics in Cancer: Molecular Characterization of Cancer-Derived Exosomes
      in Saliva.
AB  - Exosomes are small membrane vesicles of endocytic origin that are secreted by
      most cells and detected in saliva. Pathophysiological roles for salivary exosomes
      are beginning to be recognized in diseases including cancer, highlighting
      potential biomarkers and biological functions. Since early detection of cancer is
      vital for successful treatment, salivary exosomes would be advantageous in
      achieving a better survival rate due to their ready availability and
      noninvasiveness. The use of salivary exosomes may therefore be promising in the
      accurate detection of premalignant lesions and early-stage cancers, also for
      better our understanding of the molecular basis of tumorigenesis. In this
      chapter, we review our current knowledge of salivaomics, focusing on nucleic
      acids and proteins in saliva as potential cancer biomarkers. Since salivaomics is
      a rapidly evolving field, we hope to expand frameworks toward salivary exosomes,
      integrate new and existing information, and bridge salivaomics with other
      biomedical researches. Furthermore, we would like to coin the term "saliva
      exosomics" as the next-generation salivaomics. Our goal in this chapter is to
      provide the most updated information on cancer-derived exosomes in the saliva as
      natural carriers of biomarkers and signaling molecules. Major advances include
      definitive structure analysis and molecular characterization of salivary
      exosomes. We also highlight the exosome biogenesis and cargo trafficking
      mechanisms in which recent animal studies have expanded our understanding of
      exosome-mediated transfer of cancer-derived products from distal tumor to
      salivary gland. The potential roles of the salivary exosomes in cancer
      progression and immune surveillance are also addressed.

PMID- 29054272
TI  - Insights on the HLA-Binding Peptidome in Cancer.
AB  - The intracellular compartments for proteolytic antigen processing in tumor cells
      produce peptides that are presented by MHC molecules to T cells. But first, the
      ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins
      for degradation through the proteasome. Ubiqitinated proteins are unfolded and
      fed into the barrel-shaped core of the proteasome where a collection of multiple
      different proteases cleave proteins into oligopeptides. After exiting the
      proteasome, these oligopeptides are either completely degraded into amino acids
      or trimmed at the N- and C-termini so that they bind to transporter associated
      with antigen processing (TAP). TAP translocates oligopeptides into the ER where
      they are further trimmed and may bind to MHC molecules. Resulting peptide-MHC
      complexes then travel to the cell surface for T cell recognition. Many defects or
      anomalies in the proteolytic processing of tumor-derived proteins may suppress
      the expression of peptide-MHC complexes, which plays a role in escape of tumors
      from the immune system. However, due to the general dysregulated intracellular
      machinery of tumors, many proteins are translated from unconventional RNA
      transcripts including noncoding RNA, exon-intron retentions, and alternative
      splicing. These products of translation can serve as novel peptides for T cells
      as they recognize and kill tumors.

PMID- 29054273
TI  - Preface.

PMID- 29054274
TI  - Seventeen-Year Nationwide Trends in Antihypertensive Drug Use in Denmark.
AB  - Recent trends in use of antihypertensive drugs are unknown. From Danish
      nationwide prescription data, we obtained information on primary care use of
      angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta
      blockers, diuretics, aldosterone receptor antagonists, and calcium channel
      blockers. During 1999 to 2015, the use of antihypertensive drugs per 1,000
      inhabitants/day increased from 184 to 379 defined daily doses (DDD),
      corresponding to a rise in the prevalence proportion of users from ~20% to ~35%.
      From 1999 to 2015, a notable increase was observed for angiotensin-converting
      enzyme inhibitors (from 29 to 105 DDD per 1,000 inhabitants/day ~260%) and
      angiotensin II receptor blockers (from 13 to 73 DDD per 1,000 inhabitants/day
      ~520%). For diuretics the use remained stable, with a slight decrease (from 89 to
      81 DDD per 1,000 inhabitants/day ~-10%). The use of aldosterone receptor
      antagonists increased until 2007 and remained unchanged at around 3.5 DDD per
      1,000 inhabitants/day thereafter (average change ~65%). The use of beta blockers
      doubled during the study period (from 17 to 34 DDD per 1,000 inhabitants/day
      ~100%), entirely driven by increasing use of metoprolol. Similar trends were
      observed for calcium channel blockers (from 34 to 82 DDD per 1,000
      inhabitants/day ~140%), where amlodipine drove the overall increase. In
      conclusion, antihypertensive drug use has increased remarkably during the past 2
      decades.

PMID- 29054275
TI  - Comparison of Valsalva Maneuver, Amyl Nitrite, and Exercise Echocardiography to
      Demonstrate Latent Left Ventricular Outflow Obstruction in Hypertrophic
      Cardiomyopathy.
AB  - Guidelines recommend exercise stress echocardiogram (ESE) for patients with
      hypertrophic cardiomyopathy (HC) if a 50 mm Hg gradient is not present at rest or
      provoked with Valsalva or amyl nitrite, to direct medical and surgical
      management. However, no study has directly compared all 3 methods. We sought to
      evaluate efficacy and degree of provocation of left ventricular outflow gradients
      by ESE, and compare with Valsalva and amyl nitrite. In patients with HC between
      2002 and 2015, resting echocardiograms and ESEs within 1 year were
      retrospectively reviewed. Gradients elicited by each provocation method were
      compared. Rest and ESE were available in 97 patients (mean age 54 +/- 18 years,
      57% male); 78 underwent Valsalva maneuver and 41 amyl nitrite provocation. Median
      gradients (interquartile range) were 10 mm Hg (7,19) at rest, 16 mm Hg (9,34)
      with Valsalva, 23 mm Hg (13,49) with amyl nitrite, and 26 mm Hg (13,58) with ESE.
      ESE and amyl nitrite were able to provoke obstruction (>=30 mm Hg) and severe
      obstruction (>=50 mm Hg) more frequently than Valsalva. In patients with resting
      gradient <30 mm Hg (n = 83), provocation maneuvers demonstrated dynamic
      obstruction in 51%; in those with Valsalva gradient <30 mm Hg (n = 57), ESE or
      amyl nitrite provoked a gradient in 44%; and in those with amyl nitrite gradient
      <30 mm Hg (n = 20), ESE provoked a gradient in 29%. No demographic or baseline
      echocardiographic parameter predicted provocable obstruction. In conclusion, ESE
      is clinically useful; however, different provocation maneuvers may be effective
      in different patients with HC, and all maneuvers may be required to provoke
      dynamic obstruction in symptomatic patients.

PMID- 29054276
TI  - Endoscopic anti-reflux devices (with videos).

PMID- 29054277
TI  - All zirconia resin-bonded fixed dental prostheses replacing missing incisors
      probably have a high 10-year survival rate in patients who are highly compliant.

PMID- 29054278
TI  - 37% silver diamine fluoride is more effective than 12% silver diamine fluoride in
      arresting caries in the primary dentition.

PMID- 29054279
TI  - Pulpotomy, partial pulpectomy, and total pulpectomy reduced pain and thermal and
      chewing sensitivity in patients with molars with irreversible pulpitis.

PMID- 29054280
TI  - Topical anesthetics may result in more pain and need for rescue anesthetics than
      infiltrative anesthetics in patients undergoing scaling and root planing.

PMID- 29054282
TI  - Insufficient evidence to support the lack of association between bone defects and
      hard-tissue and soft-tissue outcomes of immediate implants in the posterior zone.

PMID- 29054281
TI  - Insufficient evidence about the benefits of using systemic azithromycin as an
      adjunct to open-flap debridement in patients with peri-implantitis.

PMID- 29054283
TI  - Desmin expression profile in reactive astrocytes in the 3-nitropropionic acid
      lesioned striatum of rat: Characterization and comparison with glial fibrillary
      acidic protein and nestin.
AB  - Desmin, a muscle-specific, type-III intermediate-filament protein, is reportedly
      expressed in astrocytes in the central nervous system. These cells become
      reactive astrocytes in response to brain injuries. To elucidate whether desmin is
      involved in this process, we examined the spatiotemporal expression profiles of
      desmin and their relationship with two astroglial intermediate filaments, glial
      fibrillary acidic protein (GFAP) and nestin, in the striatum of rats treated with
      the mitochondrial toxin 3-nitropropionic acid (3-NP). Weak, constitutive
      immunoreactivity for desmin was observed in astrocytes generally, and in reactive
      astrocytes in the peri-lesional area, its expression increased in parallel with
      that of GFAP over 3 d post-lesion and was maintained until at least day 28.
      Desmin, GFAP, and nestin showed characteristic time-dependent expression patterns
      in reactive astrocytes forming the astroglial scar; delayed and long-lasting
      induction of desmin and GFAP, and rapid but transient induction of nestin. In the
      lesion core, desmin was expressed in two categories of perivascular cells: nestin
      negative and nestin-positive. These findings show that desmin, together with GFAP
      and nestin, is a dynamic component of intermediate filaments in activated
      astroglia, which may account for the dynamic structural changes seen in these
      cells in response to brain injuries.

PMID- 29054284
TI  - The extended evolutionary synthesis and addiction: the price we pay for
      adaptability.
AB  - Humans are more likely to become addicted and to stay addicted than are other
      animals. This chapter is a neurobiological and molecular review of addiction and
      the cooccurring traits and psychiatric disorders from the perspective of the
      Extended Evolutionary Synthesis (EES). Addiction is an example of pleiotropy as
      many common haplotypes that are associated with individual differences in
      vulnerability to substance dependence express a variety of important brain-based
      phenotypes such as neuroadaptive processes. The neurochemical mechanisms of
      addiction are shared with behavioral flexibility and the ability to innovate,
      which are hallmark features of our species. The dopaminergic system provides a
      link between addiction and the cooccurring traits and psychiatric disorders
      evident in the shared genetic profile. A hypofunctioning dopaminergic system is
      also a common characteristic feature of addiction and the cooccurring traits and
      psychiatric disorders. Epigenetics allows for environmental factors to create
      lasting and heritable phenotypic changes enabling rapid adaptation to an
      environment. Addiction "high-jacks" this system as well as the neurochemical
      mechanisms that control flexibility and innovation and is, thus, the price we pay
      for adaptability.

PMID- 29054285
TI  - Paraventricular thalamus: Gateway to feeding, appetitive motivation, and drug
      addiction.
AB  - This chapter reviews the anatomical and functional evidence demonstrating the
      contribution of the paraventricular thalamic nucleus (PVT) to appetitive
      motivation, food intake control, and drug-seeking behaviors. We first consider
      the anatomical properties of the PVT to highlight its relevance in the control of
      appetitive motivation, feeding, and drug seeking. This is followed by a review of
      the available literature on PVT neurocircuitry, PVT involvement in food intake
      control, animal models of drug self-administration, withdrawal, and relapse. We
      show that PVT occupies a strategic position as a major thalamic interface between
      hindbrain and hypothalamic regions for viscerosensation and energy states; and
      between amygdala, cortical, and ventral striatal regions for motivation, reward,
      and learning. Understanding the precise anatomical and functional organization of
      these trans-PVT pathways remains a key challenge. Nonetheless, we show that PVT
      may be profitably viewed as the thalamic gateway to appetitive motivation,
      feeding, and drug addiction allowing both bottom-up (from brainstem and
      hypothalamus) and top-down (from cortex) control over reward and motivation.

PMID- 29054286
TI  - Functional roles of orexin/hypocretin receptors in reward circuit.
AB  - Since its first discovery in 1998, it has become clear that the orexinergic
      system plays an important role in regulating a number of functions including
      food, sex, social connections, and most prominently reward-related behaviors.
      Orexinergic neurons in the lateral hypothalamus project extensively to other
      brain areas, two most important of which are the ventral tegmental area and the
      nucleus accumbens that are involved in reward processing. In this review, we have
      presented the work in our laboratory along with the work of others and have
      discussed the possible functions we can infer from the research. We discuss the
      anatomy of the orexinergic system and its components followed by a presentation
      of other connected brain areas. The second part of this review discusses observed
      results from the morphine conditioned place preference test that sheds light on
      the possible role of the involved areas in reward processing. The complex
      circuits involved in reward processing are only beginning to be understood and we
      need to deepen our understanding regarding the nature of the interactions between
      all brain areas involved.

PMID- 29054287
TI  - Differential modulatory effects of cocaine on marmoset monkey recognition memory.
AB  - Acute and repeated exposure to cocaine alters the cognitive performance of humans
      and animals. How each administration schedule affects the same memory task has
      yet to be properly established in nonhuman primates. Therefore, we assessed the
      performance of marmoset monkeys in a spontaneous object-location (SOL)
      recognition memory task after acute and repeated exposure to cocaine (COC;
      5mg/kg, ip). Two identical neutral stimuli were explored on the 10-min sample
      trial, after which preferential exploration of the displaced vs the stationary
      object was analyzed on the 10-min test trial. For the acute treatment, cocaine
      was given immediately after the sample presentation, and spatial recognition was
      then tested after a 24-h interval. For the repeated exposure schedule, daily
      cocaine injections were given on 7 consecutive days. After a 7-day drug-free
      period, the SOL task was carried out with a 10-min intertrial interval. When
      given acutely postsample, COC improved the marmosets' recognition memory, whereas
      it had a detrimental effect after the repeated exposure. Thus, depending on the
      administration schedule, COC exerted opposing effects on the marmosets' ability
      to recognize spatial changes. This agrees with recent studies in rodents and the
      recognition impairment seen in human addicts. Further studies related to the
      effects of cocaine's acute*prior drug history on the same cognitive domain are
      warranted.

PMID- 29054288
TI  - Using the research domain criteria (RDoC) to conceptualize impulsivity and
      compulsivity in relation to addiction.
AB  - Nomenclature for mental disorder was updated in 2013 with the publication of the
      fifth edition of the Diagnostic and Statistical Manual (DSM-5). In DSM-5,
      substance use disorders are framed as more dimensional. First, the distinction
      between abuse and dependence is replaced by substance use. Second, the addictions
      section now covers both substances and behavioral addictions. This contemporary
      move toward dimensionality and transdiagnosis in the addictions and other
      disorders embrace accumulating cognitive-affective neurobiological evidence that
      is reflected in the United States' National Institutes of Health Research Domain
      Criteria (NIH RDoC). The RDoC calls for the further development of
      transdiagnostic approaches to psychopathy and includes five domains to improve
      research. Additionally, the RDoC suggests that these domains can be measured in
      terms of specific units of analysis. In line with these suggestions, recent
      publications have stimulated updated neurobiological conceptualizations of two
      transdiagnostic concepts, namely impulsivity and compulsivity and their
      interactions that are applicable to addictive disorders. However, there has not
      yet been a review to examine the constructs of impulsivity and compulsivity in
      relation to addiction in light of the research-oriented RDoC. By doing so it may
      become clearer as to whether impulsivity and compulsivity function
      antagonistically, complementarily or in some other way at the behavioral,
      cognitive, and neural level and how this relationship underpins addiction. Thus,
      here we consider research into impulsivity and compulsivity in light of the
      transdiagnostic RDoC to help better understand these concepts and their
      application to evidence-based clinical intervention for addiction.

PMID- 29054289
TI  - Cross-talk between the epigenome and neural circuits in drug addiction.
AB  - Drug addiction is a behavioral disorder characterized by dysregulated learning
      about drugs and associated cues that result in compulsive drug seeking and
      relapse. Learning about drug rewards and predictive cues is a complex process
      controlled by a computational network of neural connections interacting with
      transcriptional and molecular mechanisms within each cell to precisely guide
      behavior. The interplay between rapid, temporally specific neuronal activation,
      and longer-term changes in transcription is of critical importance in the
      expression of appropriate, or in the case of drug addiction, inappropriate
      behaviors. Thus, these factors and their interactions must be considered
      together, especially in the context of treatment. Understanding the complex
      interplay between epigenetic gene regulation and circuit connectivity will allow
      us to formulate novel therapies to normalize maladaptive reward behaviors, with a
      goal of modulating addictive behaviors, while leaving natural reward-associated
      behavior unaffected.

PMID- 29054290
TI  - Addictive behaviors: Why and how impaired mental time matters?
AB  - Mental time travel (MTT) allows navigation into the past, the future, and the
      minds of others, and it subserves future-oriented decision-making. Impaired MTT
      has been associated with a tendency to over-rely on the present, which is a
      characteristic of addictive behaviors. We here discuss the possible relationship
      between impaired autographical memory, future-oriented MTT, shortened time
      horizons, suboptimal social cognition, and poor decision-making in individuals
      with drug and gambling use disorders. We elaborate on how impaired MTT could
      compromise the process of change in addiction recovery and the effectiveness of
      psychotherapy. We argue that facilitating MTT represents, for individuals with
      addictive behaviors, an important process to enhance readiness to change, and to
      improve the quality and the efficiency of psychosocial interventions that focus
      on "emotional correction."

PMID- 29054292
TI  - Addiction: A dysregulation of satiety and inflammatory processes.
AB  - Over the years, drug addiction has proven to be a perplexing conundrum for
      scientists. In attempts to decipher the components of the puzzle, multiple
      theories of addiction have been proposed. While these theories have assisted in
      providing essential fundamental information, current research recommends that a
      new theory needs to be presented taking into consideration the results of recent
      developments in the fields of neuroimmunology, genetics, and neuropsychiatry.
      After extensively examining the published literature, we propose in this review
      that neuroinflammation and hypothalamic functioning strongly underpin addictive
      behavior. To substantiate this notion, we typed the search-string "cocaine
      addiction, hypothalamus, and inflammation" into PubMed and Google Scholar. 50 and
      1280 results were obtained in PubMed and Google Scholar, respectively. All
      article abstracts were perused for relevance to this review and 177 articles were
      used. Recent studies have purported that both acute and chronic psychostimulant
      use can activate specific components of the innate immune system. Findings such
      as these provide the scientific evidence supporting a hypothesis that includes a
      role for the innate immune system and inflammation in addictive behavior.
      However, the pathophysiological mechanisms by which they mediate the development
      of addiction have not been clearly delineated. The following review particularly
      focuses on the lateral hypothalamus and its functioning in satiety, and how
      inflammatory processes in the brain may contribute to addiction.

PMID- 29054291
TI  - Neuroscience-informed psychoeducation for addiction medicine: A neurocognitive
      perspective.
AB  - Psychoeducation (PE) is defined as an intervention with systematic, structured,
      and didactic knowledge transfer for an illness and its treatment, integrating
      emotional and motivational aspects to enable patients to cope with the illness
      and to improve its treatment adherence and efficacy. PE is considered an
      important component of treatment in both medical and psychiatric disorders,
      especially for mental health disorders associated with lack of insight, such as
      alcohol and substance use disorders (ASUDs). New advancements in neuroscience
      have shed light on how various aspects of ASUDs may relate to neural processes.
      However, the actual impact of neuroscience in the real-life clinical practice of
      addiction medicine is minimal. In this chapter, we provide a perspective on how
      PE in addiction medicine can be informed by neuroscience in two dimensions:
      content (knowledge we transfer in PE) and structure (methods we use to deliver
      PE). The content of conventional PE targets knowledge about etiology of illness,
      treatment process, adverse effects of prescribed medications, coping strategies,
      family education, and life skill training. Adding neuroscience evidence to the
      content of PE could be helpful in communicating not only the impact of drug use
      but also the beneficial impact of various treatments (i.e., on brain function),
      thus enhancing motivation for compliance and further destigmatizing their
      symptoms. PE can also be optimized in its "structure" by implicitly and
      explicitly engaging different neurocognitive processes, including
      salience/attention, memory, and self-awareness. There are many interactions
      between these two dimensions, structure and content, in the delivery of
      neuroscience-informed psychoeducation (NIPE). We explore these interactions in
      the development of a cartoon-based NIPE to promote brain recovery during
      addiction treatment as a part of the brain awareness for addiction recovery
      initiative.

PMID- 29054294
TI  - Preface.

PMID- 29054295
TI  - Diagnostic accuracy of ultrasound in patients with gout: A meta-analysis.
AB  - OBJECTIVE: This study aimed to evaluate the diagnostic performance of ultrasound
      (US) for patients with gout. METHODS: We searched the Medline, Embase, Pubmed,
      and Cochrane Library databases, and performed a meta-analysis of the diagnostic
      accuracy of US according to the double contour sign, tophus, snowstorm, or bony
      erosion in patients with gout. RESULTS: In total, 11 studies including 938
      patients with gout, and 788 controls (patients with nongout inflammatory
      arthritis) were available for the meta-analysis. The pooled sensitivity and
      specificity of US were 65.1% ([95% confidence interval (CI): 62.0-68.2] and 89.0%
      (96.6-91.1), respectively. The positive likelihood ratio, negative likelihood
      ratio, and diagnostic odds ratio were 5.889 (3.365-10.30), 0.359 (0.266-0.485),
      and 17.61 (11.11-17.92), respectively. The area under the curve of US was 0.858
      and the Q* index was 0.789, indicating good diagnostic accuracy. Some between
      study heterogeneity was found in the meta-analyses. Meta-regression showed that
      the sample size, study design, and diagnostic criteria were not sources of
      heterogeneity, and subgroup meta-analyses did not change the overall diagnostic
      accuracy. US signs of tophus, snowstorm, or bony erosion besides the double
      contour sign were not sensitive (54.3%, 30.8%, and 51.6%), but specific (93.2%,
      90.6%, and 93.3%) enough as a diagnostic tool. CONCLUSIONS: Our meta-analysis of
      published studies demonstrates that US offers good diagnostic accuracy with high
      specificity and can play an important role in the diagnosis of gout.

PMID- 29054293
TI  - Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking
      behavior.
AB  - The idea that interconnected neuronal ensembles code for specific behaviors has
      been around for decades; however, recent technical improvements allow studying
      these networks and their causal role in initiating and maintaining behavior. In
      particular, the role of ensembles in drug-seeking behaviors in the context of
      addiction is being actively investigated. Concurrent with breakthroughs in
      quantifying ensembles, research has identified a role for synaptic glutamate
      spillover during relapse. In particular, the transient relapse-associated changes
      in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia
      and extracellular matrix, are key elements of the synaptic plasticity encoded by
      drug use and the metaplasticity induced by drug-associated cues that precipitate
      drug-seeking behaviors. Here, we briefly review the recent discoveries related to
      ensembles in the addiction field and then endeavor to link these discoveries with
      drug-induced striatal plasticity and cue-induced metaplasticity toward deeper
      neurobiological understandings of drug seeking.

PMID- 29054296
TI  - Summary of fifth annual EAPM conference in Barcelona 2017.

PMID- 29054297
TI  - Hemolytic uremic syndrome due to Shiga toxin-producing Escherichia coli
      infection.
AB  - The leading cause of hemolytic uremic syndrome (HUS) in children is Shiga toxin
      producing Escherichia coli (STEC) infection, which has a major outbreak
      potential. Since the early 2010s, STEC epidemiology is characterized by a decline
      of the historically predominant O157 serogroup and the emergence of non-O157
      STEC, especially O26 and O80 in France. STEC contamination occurs through the
      ingestion of contaminated food or water, person-to-person transmission, or
      contact with ruminants or their contaminated environment. The main symptom is
      diarrhea, which is bloody in about 60% of patients and occurs after a median
      incubation period of three days. Shiga toxins released by STEC induce a cascade
      of thrombogenic and inflammatory changes of microvascular endothelial cells. HUS
      is observed in 5-15% of STEC infection cases, defined by the triad of mechanical
      hemolytic anemia, thrombocytopenia, and acute renal injury. The diagnosis of STEC
      infection relies on biological screening for Shiga toxins and STEC in stools and
      serology. Treatment of STEC-HUS is mainly symptomatic, as no specific drug has
      proved effective. The effect of antibiotics in STEC infection and STEC-HUS
      remains debated; however, some bacteriostatic antibiotics might have a beneficial
      effect. Proofs of evidence of a benefit from complement blockade therapy in STEC
      HUS are also lacking. Clinical and bacteriological STEC-HUS surveillance needs to
      be continued. Ongoing prospective studies will document the role of
      bacteriostatic antibiotics in STEC infection and STEC-HUS, and of complement
      blockade therapy in STEC-HUS.

PMID- 29054298
TI  - Antimicrobial resistance in community-acquired urinary tract infections in Paris
      in 2015.
AB  - BACKGROUND: Urinary tract infection (UTI) is one of the most frequent community
      acquired infection. Escherichia coli resistance has been on the rise since 2000s.
      METHODS: We conducted a prospective multicenter cohort study including adults who
      had a positive urine cytobacteriological examination (UCBE) performed in our
      Parisian suburb laboratory platform from October 2014 to March 2015. RESULTS: A
      total of 1223 patients were included: 995 (81.4%) women and 228 (18.6%) men. Gram
      negative bacilli were isolated in 91% of cases: E. coli accounted for 69.4% of
      cases. Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE)
      prevalence was 4.2%. Resistance of ESBL-producing E. coli strains to amoxicillin,
      fluoroquinolones, nitrofurantoin, and fosfomycin was respectively 100%, 80%, <5%,
      and <10%. Risk factors for bacteriuria caused by ESBL-PE were older age (OR=3.7
      [1.99-14.4]; P=0.02), recurrent UTI (OR=3.7 [1.9-7.2]; P=0.05), immunosuppression
      (OR=9.2 [4.1-19.47]; P=0.01), recent hospitalization within the last three months
      (OR=4.5 [2.3-8.3]; P=0.05), and recent antibiotic therapy (OR=13.4 [6.29-31.9];
      P<0.01). CONCLUSION: The prevalence of ESBL-PE bacteriuria seems to be 4%. Older
      age, immunosuppression, recurrent UTI, recent hospitalization, and antibiotic
      therapy are the main risk factors associated with ESBL-PE community-acquired UTI.

PMID- 29054299
TI  - Implementation of educational programs to prevent drowning. What can be done in
      nursery school?

PMID- 29054300
TI  - Why Might Bacterial Pathogens Have Small Genomes?
AB  - Bacteria that cause serious disease often have smaller genomes, and fewer genes,
      than their nonpathogenic, or less pathogenic relatives. Here, we review evidence
      for the generality of this association, and summarise the various reasons why the
      association might hold. We focus on the population genetic processes that might
      lead to reductive genome evolution, and show how several of these could be
      connected to pathogenicity. We find some evidence for most of the processes
      having acted in bacterial pathogens, including several different modes of genome
      reduction acting in the same lineage. We argue that predictable processes of
      genome evolution might not reflect any common underlying process.

PMID- 29054301
TI  - Environmental Filtering Is a Relic. A Response to Cadotte and Tucker.

PMID- 29054302
TI  - Monitoring the biomechanical and physiological effects of postural changes during
      leisure chair sitting.
AB  - BACKGROUND: Individuals with limited mobility can spend prolonged periods in
      leisure chairs, increasing their risk of developing a seated acquired pressure
      ulcer. The present study aims to use objective measures of posture and tissue
      viability to identify the associated risks of leisure chair related pressure
      ulcers. METHODS: Healthy participants (n = 13) were recruited to sit on a leisure
      chair with either a viscoelastic foam or air cushion. Participants were asked to
      adopt four different postures for a period of 10 min followed by a 10 min
      refractory period. Measurements at the leisure chair-participant interface
      included interface pressure, transcutaneous tissue gas tensions at the ischial
      tuberosities, accelerometer data collected from the sternum and subjective
      comfort levels. RESULTS: Results indicated that interface pressures remained
      consistent, with peak pressure index values of less than 60 mmHg across all
      conditions. A proportion of participants exhibited decreased oxygen tensions
      associated with increased carbon dioxide tensions during one or more test
      condition. This was particularly prevalent during the right lean posture on the
      air cushion (46%). In all cases, normal tissue viability was restored during
      standing. The accelerometer was able to detect significant changes (p < 0.05) in
      relative trunk angles during slump and right lean when compared to optimal
      sitting posture. CONCLUSION: Commercially available leisure chairs have little
      evidence to support their pressure relieving properties. This study revealed that
      a proportion of healthy individuals demonstrated a compromised tissue viability
      in specific postures. Further research is required to assess the impact of these
      sitting conditions in vulnerable individuals.

PMID- 29054303
TI  - Cost Savings of Standardization of Thoracic Surgical Instruments: The Process of
      Lean.
AB  - BACKGROUND: Our objective is to show the effect that standardization of surgical
      trays has on the number of instruments sterilized and on cost. METHODS: We
      reviewed our most commonly used surgical trays with the 3 general thoracic
      surgeons in our division and agreed upon the least number of surgical instruments
      needed for mediastinoscopy, video-assisted thoracoscopic surgery, robotic
      thoracic surgery, and thoracotomy. RESULTS: We removed 59 of 79 instruments (75%)
      from the mediastinoscopy tray, 45 of 73 (62%) from the video-assisted
      thoracoscopic surgery tray, 51 of 84 (61%) from the robotic tray, and 50 of 113
      (44%) from the thoracotomy tray. From January 2016 to December 2016, the
      estimated savings by procedure were video-assisted thoracoscopic surgery (n =
      398) $21,890, robotic tray (n = 231) $19,400, thoracotomy (n = 163) $15,648, and
      mediastinoscopy (n = 162) $12,474. Estimated total savings were $69,412. The
      weight of the trays was reduced 70%, and the nonsteamed sterilization rate
      (opened trays that needed to be reprocessed) decreased from 2% to 0%. None of the
      surgeons requested any of the removed instruments. CONCLUSIONS: Standardization
      of thoracic surgical trays is possible despite having multiple thoracic surgeons.
      This process of lean (the removal of nonvalue steps or equipment) reduces the
      number of instruments cleaned and carried and reduces cost. It may also reduce
      the incidence of "wet loads" that require the resterilization of instruments.

PMID- 29054304
TI  - Thoracic Endometriosis Syndrome Other Than Pneumothorax: Clinical and
      Pathological Findings.
AB  - BACKGROUND: Thoracic endometriosis syndrome refers to a broad spectrum of
      clinical manifestations related to the presence of ectopic intrathoracic
      endometrial tissue. Few studies have reported on manifestations other than
      pneumothorax. METHODS: Clinical, surgical, and pathology records of all
      consecutive women of reproductive age referred to our institution from September
      2001 to August 2016 for clinically suspected thoracic endometriosis syndrome were
      retrospectively reviewed. After excluding women with pneumothorax, we enrolled 31
      patients, divided into three subgroups: catamenial chest pain (n = 20),
      endometriosis-related diaphragmatic hernia (n = 6), and endometriosis-related
      pleural effusion (n = 5). RESULTS: Surgery was performed in 11 patients with
      catamenial thoracic pain (median age, 30 years; range, 23 to 42). Median pain
      intensity assessed on the 0 to 10 Visual Analogue Scale was 8 (range, 8 to 9)
      before surgery. At surgery, 8 patients had diaphragmatic endometriosis implants,
      which were resected with direct suture of diaphragm. At follow-up, median pain
      score was 3 (range, 0 to 8). In the group presenting with diaphragmatic hernia
      (median age, 36 years; range, 29 to 50), diaphragm was repaired by direct suture
      or placement of prosthesis in 4 and 2 cases, respectively. At follow-up, no sign
      of recurrent hernia was observed. Finally, among women with endometriosis-related
      pleural effusion (median age, 30 years; range, 25 to 42), surgical treatment was
      represented by evacuation of the pleural effusion and biopsy (n = 4) or removal
      (n = 1) of visible endometrial foci. CONCLUSIONS: Thoracic endometriosis syndrome
      is a poorly recognized entity responsible for various manifestations other than
      pneumothorax. In case of catamenial thoracic pain, diaphragmatic hernia and
      catamenial pleural effusion surgery should be advised in a multidisciplinary
      setting.

PMID- 29054305
TI  - Scimitar Syndrome in Children and Adults: Natural History, Outcomes, and Risk
      Analysis.
AB  - BACKGROUND: Scimitar syndrome involves congenital anomalous pulmonary venous
      return to the inferior vena cava. Optimal management remains controversial. We
      describe the natural history of disease, nonsurgical and surgical outcomes, and
      risk factors for poor outcomes at our institution. METHODS: Patients with
      anomalous pulmonary venous return to the inferior vena cava documented on
      echocardiography at our institution between January 1994 and January 2015 were
      reviewed retrospectively. The study protocol IRB-AAAO1805 was approved. RESULTS:
      Forty-seven patients were identified, including 20 infants with significant
      associated congenital heart defects (42.6%, including 7 with single ventricle
      physiology), and 10 infants (21.3%) and 16 noninfants (34.0%) with isolated
      scimitar syndrome. Median follow-up was 3.55 years. Noninfants exhibited lower
      incidences of right pulmonary artery hypoplasia (p < 0.001), aortopulmonary
      collaterals (p = 0.004), and scimitar vein obstruction at the caval confluence (p
      = 0.032). Eighteen patients (38.3%) underwent surgical repair for scimitar
      syndrome. Overall mortality after baffle repair or scimitar vein reimplantation
      was 37.5% (3 of 8) for infants and 0% (0 of 6) for noninfants (p = 0.209).
      Overall mortality for medically managed infants was 46.7% (7 of 15) compared with
      0% (0 of 8) for noninfants (p = 0.052). Multivariable analyses identified
      infantile onset as an independent risk factor for stenosis or obstruction after
      repair (hazard ratio 9.34, p = 0.048), and single ventricle physiology as an
      independent risk factor for mortality among unrepaired patients (hazard ratio
      29.8, p = 0.004). CONCLUSIONS: The severity of scimitar syndrome depends on
      presenting age and associated congenital heart disease. Nonsurgical and surgical
      outcomes are suboptimal for infantile disease, which is a risk factor for
      stenosis after repair. Single ventricle physiology is associated with poor
      prognosis.

PMID- 29054306
TI  - Two-Stage Surgery Without Parenchyma Resection for Endobronchial Carcinoid Tumor.
AB  - BACKGROUND: The aim of the study was to evaluate the efficacy of a combined
      approach of endoscopic resection followed by pure bronchoplasty without any
      pulmonary resection in patients with endobronchial carcinoids. METHODS: We
      applied a two-stage technique, endoscopic resection first followed by pure
      bronchoplasty, to 25 patients (10 men, 15 women) with endobronchial carcinoid
      tumors. The median age was 32.4 years (range, 19 to 64). The indications for this
      technique were pure endobronchial carcinoid without lymph node involvement. Tumor
      was located on the right side in 18 patients (72%), and on the left in 7 patients
      (28%). Flexible bronchoscopy was carried out in all patients as the first-stage
      procedure for debulking and searching for a true pedicle of the tumor. Different
      types of pure bronchoplasty were performed as the second-stage surgery with
      systematic mediastinal lymph node dissection. RESULTS: The resection was complete
      (R0) in all cases. Tumors were pathologically staged as pT1aN0 in 18 patients,
      pT2N0 in 5, and pT3N0 in 2 patients; 23 tumors were typical and only two were
      atypical carcinoids. Morbidity was 28.0% (only minor complications), with no
      mortality. Overall 5-year and 10-year survival was 100.0% and 91.8%,
      respectively. No recurrence of the primary tumor was observed in any case.
      CONCLUSIONS: Two-stage surgery consisting of endoscopic resection and pure
      bronchoplasty without lung parenchyma resection is an effective technique for the
      treatment of endobronchial carcinoid, with an excellent oncologic outcome.

PMID- 29054308
TI  - ACC/AATS/AHA/ASE/EACTS/HVS/SCA/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria
      for the Treatment of Patients With Severe Aortic Stenosis: A Report of the
      American College of Cardiology Appropriate Use Criteria Task Force, American
      Association for Thoracic Surgery, American Heart Association, American Society of
      Echocardiography, European Association for Cardio-Thoracic Surgery, Heart Valve
      Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular
      Angiography and Interventions, Society of Cardiovascular Computed Tomography,
      Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

PMID- 29054307
TI  - Early and Late Surgical Outcomes of Acute Type A Aortic Dissection in
      Octogenarians.
AB  - BACKGROUND: Although surgical outcomes of acute type A aortic dissection (ATAAD)
      have improved, it is still a high-risk procedure for octogenarians. This study
      analyzed early and late outcomes of surgical repair of ATAAD among octogenarians.
      METHODS: From 1990 through 2016, 1,260 consecutive patients with ATAAD were
      emergently admitted to Jichi Medical University Hospitals. Of them, 1,026
      patients who underwent emergency surgery for ATAAD within 48 hours of symptom
      onset were included in this retrospective study. Of these, 112 were aged 80 years
      or more (mean, 83.1 +/- 2.7) and formed the octogenarian group; and 914 were aged
      less than 80 years (mean, 62.0 +/- 11.4) and formed the control group. Early and
      late outcomes were compared. RESULTS: The inhospital mortality rate was 6.3% for
      the octogenarian group and 7.4% for the control group (p = 0.85). No significant
      difference was observed in the causes of hospital death. Although the overall
      postoperative complication rate was not different (24.1% versus 23.0%), pneumonia
      was more frequent among octogenarians (p = 0.03). Multivariate analysis of
      hospital mortality did not indicate age 80 years or more as a risk factor.
      Overall postoperative survival for the octogenarian group was 84.6%, 70.5%, and
      57.1% at 1, 3, and 5 years, respectively. For the control group, the rates were
      89.1%, 85.6%, and 82.1%, respectively. Pneumonia and decrepitude were the major
      causes of remote death for the octogenarian group. CONCLUSIONS: No significant
      difference in the hospital mortality rate or the complication rate was observed
      between the groups. Emergency surgery for ATAAD in octogenarians could be
      performed with the same low risk observed for younger patients.

PMID- 29054309
TI  - Genetically Encoded FRET Biosensors to Illuminate Compartmentalised GPCR
      Signalling.
AB  - Genetically encoded Forster resonance energy transfer (FRET) biosensors have been
      instrumental to our understanding of how intracellular signalling is organised
      and regulated within cells. In the last decade, the toolbox, dynamic range and
      applications of these sensors have expanded beyond basic cell biology
      applications. In particular, FRET biosensors have shed light onto the mechanisms
      that control the intracellular organisation of G protein-coupled receptor (GPCR)
      signalling and have allowed the visualisation of signalling events with
      unprecedented temporal and spatial resolution. Here we review the use of these
      sensors in the GPCR field and how it has already provided invaluable advances
      towards our understanding of the complexity of GPCR signalling.

PMID- 29054310
TI  - Etiology, diagnosis, and demographic analysis of maxillofacial trauma in elderly
      persons: A 10-year investigation.
AB  - PURPOSE: The aim of this study was to investigate etiologies and diagnoses of
      maxillofacial trauma in emergency services in Brazil over a period of 10 years.
      Additionally, associations among sex, age, accident location, and dependent
      variables were analyzed. Understanding the epidemiology of trauma and the
      physiology of aging is important in maintaining health and bettering service for
      the elderly population. MATERIALS AND METHODS: The primary mode of investigation
      was analysis of medical records from 2003 to 2013. These researchers recorded the
      diagnosis and etiology of the trauma, the location where the accident occurred,
      and the sex and age of the participants. Variable categories were compared using
      Chi-squared distribution, and logistic regression was used to analyze the
      associated factors. RESULTS: Of the 677 individuals analyzed, the female sex was
      predominant (57.61%) and the most prevalent age ranges were between 60 and 69
      years (40.18%) and between 70 and 79 years (35.16%). Chi-squared distribution
      showed that men suffered more fractures (18.47%, p = 0.028) and women suffered
      more contusions (21.54%, p = 0.028). With regard to the various etiologies
      related to the traumas, traffic accidents (17.77%, p < 0.001) and aggression
      (17.42%, p < 0.001) were more frequent in males, and falls (83.03%, p < 0.001)
      were more frequent in females. The primary etiologies for maxillofacial trauma in
      the elderly population were falls, and the primary diagnoses were fractures.
      CONCLUSION: A deeper understanding of the physiological changes associated with
      aging, and preventive action to reduce falls, traffic accidents, and aggression
      in this population could be beneficial with regard to quality of life for elderly
      persons.

PMID- 29054311
TI  - Transcutaneous aponeurotic repair with small detachment of the levator
      aponeurosis for aponeurotic blepharoptosis in Japanese patients.
AB  - PURPOSE: To examine the surgical outcomes of a modified transcutaneous
      aponeurotic repair for aponeurotic blepharoptosis in a Japanese population.
      METHODS: This retrospective study included 75 eyelids of 45 patients with
      aponeurotic blepharoptosis who had undergone a modified transcutaneous
      aponeurotic repair. This procedure included a long skin incision for securing a
      wide surgical field, creation of a double eyelid crease, and a small extent of
      detachment of the levator aponeurosis from the tarsal surface. Functional success
      was defined as a postoperative margin reflex distance-1 of 2-5 mm without serious
      complications at 3 months postoperatively. Cosmetic success was judged by
      achieving a <= 1-mm laterality of eyelid height, a <= 2-mm laterality of
      pretarsal show, and symmetry of the eyelid contour at 3 months postoperatively.
      RESULTS: The functional success rate was 70.7% among all patients, with 84.4%,
      86.7%, and 88.9% of patients showing cosmetic success regarding symmetry of
      eyelid height, pretarsal show, and eyelid contour, respectively. After applying
      functional and all 3 cosmetic criteria simultaneously, 28 patients (62.2%) were
      satisfied in this study. No serious complications occurred during the follow-up
      period. CONCLUSIONS: This modified procedure provided good functional and
      cosmetic outcomes for aponeurotic blepharoptosis, indicating an acceptable
      blepharoptosis repair for East Asian patients.

PMID- 29054312
TI  - Flow Bioreactors as Complementary Tools for Biocatalytic Process Intensification.
AB  - Biocatalysis has widened its scope and relevance since new molecular tools,
      including improved expression systems for proteins, protein and metabolic
      engineering, and rational techniques for immobilization, have become available.
      However, applications are still sometimes hampered by low productivity and
      difficulties in scaling up. A practical and reasonable step to improve the
      performances of biocatalysts (including both enzymes and whole-cell systems) is
      to use them in flow reactors. This review describes the state of the art on the
      design and use of biocatalysis in flow reactors. The encouraging successes of
      this enabling technology are critically discussed, highlighting new
      opportunities, problems to be solved and technological advances.

PMID- 29054314
TI  - Bedside Chest Radiographs in the Intensive care Setting: Wireless Direct
      Radiography Compared to Computed Radiography.
AB  - OBJECTIVES: To compare image quality, visibility of anatomic landmarks, tubes and
      lines, and other clinically significant findings on portable (bedside) chest
      radiographs acquired with wireless direct radiography (DRw) and computed
      radiography (CR). METHODS: In a prospective IRB-approved and HIPAA-compliant
      study, portable DRw (DRX-1C mobile retrofit portable wireless direct radiography,
      CareStream Inc., Rochester, NY) and portable CR (AGFA CR (DXG) version; NIM2103,
      AGFA Healthcare, Ridgefield Park, NJ) images of the chest were acquired within 24
      hours in 80 patients in the intensive care unit (ICU). Image pairs of 75 patients
      (37% female) with a mean age of 60.7+/-16 years were independently compared side
      by-side by 7 experienced thoracic radiologists using a five-point scale. When
      tubes and lines were present, the radiologist also compared an edge-enhanced copy
      of the DRw image to the CR image. RESULTS: Most radiologists found significantly
      fewer artifacts on DRw images compared to CR images and all readers agreed that
      when present, these artifacts did not significantly preclude the ability to
      evaluate anatomic landmarks, tubes and lines, or clinically significant findings.
      None of the radiologists (0/7) reported superior visibility of anatomic
      structures on CR images compared to DRw images and some radiologists (3/7) found
      DRw images significantly better for visibility of anatomic landmarks such as the
      carina (p=0.01-0.001). Most radiologists (6/7) found DRw images to be better or
      clearly better than CR images for position of tubes and lines, and edge-enhanced
      DRw images to be especially helpful for evaluation of central venous catheters
      and esophageal tubes (p=0.027-0.001). None of the radiologists deemed CR images
      superior for visibility of clinically significant findings. CONCLUSIONS: Critical
      care chest radiography with a portable DRw system can provide similar or superior
      information compared to a CR system regarding clinically significant findings and
      position of tubes and lines.

PMID- 29054313
TI  - Imaging Biomaterial-Tissue Interactions.
AB  - Modern biomedical imaging has revolutionized life science by providing
      anatomical, functional, and molecular information of biological species with high
      spatial resolution, deep penetration, enhanced temporal responsiveness, and
      improved chemical specificity. In recent years, these imaging techniques have
      been increasingly tailored for characterizing biomaterials and probing their
      interactions with biological tissues. This in turn has spurred substantial
      advances in engineering material properties to accommodate different imaging
      modalities that was previously unattainable. Here, we review advances in
      engineering both imaging modalities and material properties with improved
      contrast, providing a timely practical guide to better assess biomaterial-tissue
      interactions both in vitro and in vivo.

PMID- 29054315
TI  - Cord Topographical Anatomy and its Role in Evaluating Intramedullary Lesions.
AB  - Intramedullary spinal lesions present a wide differential diagnosis including
      infectious, inflammatory, traumatic, ischemic, benign, or malignant neoplastic
      etiologies. Using knowledge of anatomy and physiology within the spinal cord,
      many similar appearing entities can be parsed into a prioritized differential.
      The purpose of this article is to review anatomy and pathophysiology of the
      spinal cord, with subsequent discussion of how this knowledge can be used to
      differentiate several similar appearing intramedullary pathologic processes.
      Discussion includes the pathophysiology, imaging findings, and clinical pearls of
      several intramural lesions including infarct, demyelinating lesions, traumatic
      injury, neoplasm, vascular malformation, and metabolic processes such as subacute
      combined degeneration.

PMID- 29054316
TI  - Model predictive control for systems with fast dynamics using inverse neural
      models.
AB  - In this work, a novel model predictive control (MPC) scheme is introduced, by
      integrating direct and indirect neural control methodologies. The proposed
      approach makes use of a robust inverse radial basis function (RBF) model taking
      into account the applicability domain criterion, in order to provide a suitable
      initial starting point for the optimizer, thus helping to solve the optimization
      problem faster. The performance of the proposed controller is evaluated on the
      control of a highly nonlinear system with fast dynamics and compared with
      different control schemes. Results show that the proposed approach outperforms
      the rivaling schemes in terms of response; moreover, it solves the optimization
      problem in less than one sampling period, thus effectively rendering MPC-based
      controllers capable of handling systems with fast dynamics.

PMID- 29054317
TI  - Acute hepatitis as a manifestation of secondary syphilis.

PMID- 29054318
TI  - Leukocytoclastic vasculitis complicating adalimumab therapy for Crohn's disease:
      Report of three cases.

PMID- 29054319
TI  - Granulomatous gastritis induced by onychophagia: First case report.

PMID- 29054320
TI  - Eradication of Helicobacter pylori infection with a new bismuth-based quadruple
      therapy in clinical practice.
AB  - INTRODUCTION: The eradication of Helicobacter pylori infection represents a
      clinical challenge. OBJECTIVE: To evaluate the efficacy and safety of quadruple
      therapy with esomeprazole plus a 3-in-1 capsule containing bismuth subcitrate,
      metronidazole and tetracycline, plus probiotics in patients diagnosed with H.
      pylori infection in routine clinical practice. METHODS: A prospective,
      interventional, single-centre and open-label study in consecutive patients with a
      confirmed indication for eradication of H. pylori infection. Patients were
      treated with three capsules of Pylera(r) four times a day (breakfast, lunch,
      afternoon snack and dinner), plus 40mg of esomeprazole twice daily for 10 days
      (30min before breakfast and dinner) and probiotics for 30 days. Eradication of H.
      pylori infection was confirmed by labelled urea breath test performed at least 28
      days after the end of treatment. RESULTS: A total of 100 patients were
      consecutively enrolled. Twenty-five patients (25.0%) had a prior history of
      treatment for their H. pylori infection. In the intention-to-treat population,
      eradication rates were 90.7% (68/75) and 80.0% (20/25) in patients treated with
      Pylera(r) as the first line or as rescue therapy, respectively. Eighteen patients
      (18%) had at least one adverse event, most of which (89%) were mild. CONCLUSION:
      Ten days of treatment with a quadruple regimen of bismuth, metronidazole and
      tetracycline plus esomeprazole and probiotics is an effective and safe strategy
      in patients with H. pylori infection.

PMID- 29054321
TI  - Noradrenaline as an alternative medical treatment to terlipressin in the
      management of hepatorenal syndrome type 1.

PMID- 29054322
TI  - Intestinal perforation secondary to intestinal diffuse large b-cell lymphoma in a
      patient with coeliac disease.

PMID- 29054323
TI  - Human kidney stone matrix: Latent potential to restrain COM induced cytotoxicity
      and inflammatory response.
AB  - Kidney stone disease is a multi-factorial disorder resulting from the interplay
      of various risk factors including lifestyle, environment and genetics along with
      metabolic activities inside the body. However, it is difficult to determine how
      these factors converge to promote stone disease. Extensive investigations of
      kidney stone composition at the molecular level have been carried out however;
      its impact on the complex mechanism of stone formation is still obscure. Hence,
      an in vitro study was designed to investigate the attenuation of calcium oxalate
      toxicity by human kidney stone matrix proteins on NRK-52E cells using
      flowcytometry, Western blotting, RT-PCR and immunofluorescence assays.
      Morphological alterations in cell-crystal interaction were assessed using
      scanning electron microscopy. Microscopic studies showed profound impairment of
      COM crystal structure as a consequence of protein-crystal interactions. RT-PCR
      analysis and immunocytochemistry of NRK-52E cells revealed the up-regulation of
      inflammatory and stress biomarkers OPN and HSP-70, respectively, in response to
      COM toxicity; which diminished significantly in the presence of kidney stone
      matrix proteins. The results of present study propose that the mechanism
      undertaken by matrix proteins to attenuate COM induced cytotoxicity could be
      attributed to the modulation of crystal structure, which subsequently restraint
      the inflammatory response and apoptotic cell death. The inference drawn through
      this study could provide better understanding of the intricate process of kidney
      stone formation.

PMID- 29054324
TI  - Protective role of chrysin on 6-hydroxydopamine-induced neurodegeneration a mouse
      model of Parkinson's disease: Involvement of neuroinflammation and neurotrophins.
AB  - Chrysin is a natural flavonoid which is found in bee propolis, honey and various
      plants, and neuroprotective effect of chrysin in mice was previously demonstrated
      by our group. Neuroinflammation, neurotrophic factors and neuronal recovery
      factors associated with the neuroprotective effect of this flavonoid require
      further investigations. Thus, now we investigated the possible involvement of
      inflammatory cytokines, neurotrophic factors and neuronal recovery in the effect
      of chrysin in 6-hydroxidopamine (6-OHDA), a well-established model of Parkinson's
      disease, in striatum of mice. The 6-OHDA microinjection induced behavioral
      alterations on the rotarod test and apomorphine-induced circling behavior in
      mice. 6-OHDA administration elevated levels of tumour necrosis factor-alpha,
      interferon-gamma, interleukin-1beta, interleukin-2, interleukin-6 and nuclear
      factor-kappa B and decreased the interleukin-10 levels, total reactive
      antioxidant potential and total antioxidant reactivity in striatum, as well as,
      modified the calcium-binding protein B (S100B), brain-derived neurotrophic
      factor, nerve growth factor and glial cell line-derived neurotrophic factor
      levels. The intrastriatal injection of 6-OHDA also induced an decrease of
      dopamine, 3,4-dihydroxyphenylacetic acid, homovanylic acid levels and tyrosine
      hydroxylase content. Oral treatment with chrysin (10 mg/kg, 28 days), culminated
      with the prevention of these alterations occasioned by 6-OHDA. These results
      corroborated with the neuroprotective effect of chrysin in the treatment of
      Parkinson's disease and, indicated the mechanism involved throught the
      inflammatory cytokines, neurotrophic factors and recovery of dopaminergic neurons
      in striatum.

PMID- 29054326
TI  - Development and validation of the comprehensive praxis assessment for children
      aged 6-8.
AB  - This study examined the psychometric properties of motor praxis using a large
      school-based sample of children (n=239). We developed and evaluated the construct
      validity of a motor praxis assessment using confirmatory factor analysis (CFA). A
      model with four latent variables was evaluated for goodness of fit. CFA
      established that the scale was multifactorial and supported the four-factor model
      (motor imagery, verbal gesture production, imitative gesture production and
      knowledge of object-use). The internal consistency, inter-rater reliability and
      concurrent validity of the praxis assessment mostly demonstrated good to
      excellent results for the full scale and the subscales. The motor praxis
      demonstrated an ontogenic progression in 6-, 7- and 8-year-olds, suggesting a
      developmental trend during these ages, but with the exception of gestural
      representation on imitation. Implications for motor development and clinical
      evaluation are discussed herein in relation to the four instruments.

PMID- 29054325
TI  - Use of 'ideal' alveolar air equations and corrected end-tidal PCO2 to estimate
      arterial PCO2 and physiological dead space during exercise in patients with heart
      failure.
AB  - BACKGROUND: Arterial CO2 tension (PaCO2) and physiological dead space (VD) are
      not routinely measured during clinical cardiopulmonary exercise testing (CPET).
      Abnormal changes in PaCO2 accompanied by increased VD directly contribute to
      impaired exercise ventilatory function in heart failure (HF). Because arterial
      catheterization is not standard practice during CPET, this study tested the
      construct validity of PaCO2 and VD prediction models using 'ideal' alveolar air
      equations and basic ventilation and gas-exchangegas exchange measurements during
      CPET in HF. METHODS: Forty-seven NYHA class II/III HF (LVEF=21+/-7%; age=55+/
      9years; male=89%; BMI=28+/-5kg/m2) performed step-wise cycle ergometry CPET to
      volitional fatigue. Breath-by-breath ventilation and gas exchange were measured
      continuously. Steady-state PaCO2 was measured at rest and peak exercise via
      radial arterial catheterization. Criterion VD was calculated via 'ideal' alveolar
      equations, whereas PaCO2 or VD models were based on end-tidal CO2 tension
      (PETCO2), tidal volume (VT), and/or weight. RESULTS: Criterion measurements of
      PaCO2 (38+/-5 vs. 33+/-5mmHg, P<0.01) and VD (0.26+/-0.07 vs. 0.41+/-0.15L,
      P<0.01) differed at rest vs. peak exercise, respectively. The equation,
      5.5+0.90*PETCO2-0.0021*VT, was the strongest predictor of PaCO2 at rest and peak
      exercise (bias+/-95%LOA=-3.24+/-6.63 and -0.98+/-5.76mmHg; R2=0.57 and 0.75,
      P<0.001, respectively). This equation closely predicted VD at rest and peak
      exercise (bias+/-95%LOA=-0.03+/-0.06 and -0.02+/-0.13L; R2=0.86 and 0.83,
      P<0.001, respectively). CONCLUSIONS: These data suggest predicted PaCO2 and VD
      based on breath-by-breath gas exchange and ventilatory responses demonstrate
      acceptable agreement with criterion measurements at peak exercise in HF patients.
      Routine assessment of PaCO2 and VD can be used to improve interpretability of
      exercise ventilatory responses in HF.

PMID- 29054327
TI  - Sex differences in anticipatory postural adjustments during rapid single leg
      lift.
AB  - The aim of this study was to assess the influence of sex on the kinetic,
      kinematic and neuromuscular correlates of anticipatory postural adjustments
      (APAs) during a single leg lift task performed by healthy participants. Fifty
      healthy age and body mass index matched participants (25 women and 25 men)
      performed 20 single leg lift task (hip flexion to 90  degrees  as quickly as
      possible) with their dominant and their non-dominant lower limbs. A force plate
      was used to determine the medial-lateral displacement of the center of pressure
      (COPML), and the initiation of weight shift (T0); kinematics was used to
      determine leg lift (T1); and electromyography was used to determine onset times
      from eight muscles: bilateral external oblique, internal oblique and lumbar
      multifidus, and unilateral (stance limb) gluteus maximus and biceps femoris.
      Movement control limb dominance was included in the analysis. Statistically
      significant interactions between sex and limb dominance (p < .001) were observed
      for T1, COPML, and muscle onsets. Also, statistically significant main effect of
      sex on T0 was observed. Women showed increased APA time (T1) and magnitude
      (COPML) in their dominant limbs compared to men. Such differences between sexes
      did not occur in the non-dominant limb. Women recruited proximal muscles later
      than their man counterparts. Overall, women appear to have a stronger effect of
      limb dominance on their anticipatory postural control strategy which requires
      further investigation. The findings of the current study indicate that women and
      men differ in their anticipatory postural control strategy for rapid single leg
      lift.

PMID- 29054328
TI  - Ependymomas arising outside of the central nervous system: A case series and
      literature review.
AB  - BACKGROUND: Extracranial and extraspinal ependymomas are extremely rare tumors
      mostly published in the literature as case reports. METHODS: MD Anderson Cancer
      Center institutional database was screened for patients with extra CNS
      ependymomas over a 25 year period. RESULTS: Eight patients with extra CNS
      ependymoma were identified. Five cases originated in the sacrum or subcutaneous
      sacral area, and the other 3 cases originating in the breast, lung and adnexa of
      the uterus. By histology, most cases were myxopapillary ependymomas (5 cases), 2
      cases were grade II ependymoma and 1 case was an anaplastic ependymoma.
      Metastases occurred in 6 cases and 3 patients died due to progressive disease.
      Most cases required surgery, radiation and chemotherapy. CONCLUSION: Extra CNS
      ependymomas are very rare tumors that tend to metastasize, even though most cases
      are histologically classified as low grade ependymomas.

PMID- 29054329
TI  - The optimal stimulation site for high-frequency repetitive transcranial magnetic
      stimulation in Parkinson's disease: A double-blind crossover pilot study.
AB  - Many reports have shown improvements in motor symptoms after repetitive
      transcranial magnetic stimulation (rTMS). However, the best stimulation area in
      the brain has not currently been determined. We assessed the effects of high
      frequency rTMS (HF-rTMS) on the motor and mood disturbances in Parkinson's
      disease (PD) patients and attempted to determine whether the primary motor area
      (M1), the supplementary motor area (SMA), and the dorsolateral prefrontal cortex
      (DLPFC) were the best treatment targets. In this randomized, double-blind
      crossover design study, we investigated the efficacy of 3 consecutive days of HF
      rTMS over the M1, SMA, and DLPFC and compared these HF-rTMS to sham stimulations.
      We used motor and non-motor scales to evaluate the parkinsonian symptoms. The
      changes in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III)
      scores after the application of HF-rTMS over the M1 and SMA were significantly
      greater than those after the sham stimulation. However, after the application of
      HF-rTMS over the DLPFC, the UPDRS-III scores were similar to those after the sham
      stimulation. No significant improvements were demonstrated in the mood
      disturbances after the stimulations over any of the targets. In conclusion, the
      application of HF-rTMS over the M1 and SMA significantly improved the motor
      symptoms in the PD patients but did not alter the mood disturbances.

PMID- 29054331
TI  - Risk of hepatitis B virus reactivation in patients treated with anti-TNFalpha
      agents for immune-mediated inflammatory diseases.

PMID- 29054330
TI  - Tongue strength in patients with subacute myelo-optico-neuropathy.
AB  - Subacute myelo-optico-neuropathy (SMON) is a neurodegenerative disease that may
      be caused by overdose or prolonged oral administration of clioquinol. Recently,
      dysphagia has attracted attention as a complication of SMON. To investigate
      lingual control in SMON, we examined patients with SMON using assessments of
      maximum tongue pressure, compared with dysphagia-related diseases, such as
      sporadic inclusion body myositis (sIBM) and amyotrophic lateral sclerosis (ALS),
      and healthy volunteer. The mean maximum tongue pressure (Pmax) in patients with
      SMON was 14.7 +/- 5.8 kPa, while it was 33.6 +/- 4.4 kPa in the controls. In
      contrast, the mean Pmax for patients with ALS with or without bulbar involvement
      was 7.8 +/- 2.7 kPa and 34.4 +/- 5.7 kPa, respectively, while it was 29.4 +/- 8.2
      kPa in patients with sIBM. Pmax values correlated with lower limb weakness in
      SMON patients. Decreases in Pmax may be involved in the development of dysphagia
      in patients with SMON.

PMID- 29054332
TI  - Humanity in a Dish: Population Genetics with iPSCs.
AB  - Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the
      relationship between genotype and phenotype. Recent publications have described
      iPSC cohort studies of common genetic variants and their effects on gene
      expression and cellular phenotypes. These in vitro quantitative trait locus (QTL)
      studies are the first experiments in a new paradigm with great potential: iPSC
      based functional population genetic studies. iPSC collections from large cohorts
      are currently under development to facilitate the next wave of these studies,
      which have the potential to discover the effects of common genetic variants on
      cellular phenotypes and to uncover the molecular basis of common genetic
      diseases. Here, we describe the recent advances in this developing field, and
      provide a road map for future in vitro functional population genetic studies and
      trial-in-a-dish experiments.

PMID- 29054333
TI  - Developmental trend of children with Down's syndrome - How do sex and neonatal
      conditions influence their developmental patterns?
AB  - OBJECTIVE: This study investigated factors that would influence developmental
      trend of children with Down's syndrome (DS) in three different domains (motor,
      cognitive, language), specifically focusing on the effect of sex and neonatal
      conditions, including preterm birth, low birth weight, and congenital heart
      disease (CHD). METHODS: The participants were 158 children with DS (mean age at
      the initial test = 25.5 months) receiving clinical service at a rehabilitation
      center in Yokohama, Japan. Kyoto Scale of Psychological Development was used to
      measure developmental level, which derive total developmental age (DA), Posture
      motor DA, Cognitive-adaptive DA, and Language-social DA. For the analyses, a
      multilevel model for change was adopted, as the model allowed us to investigate
      intrapersonal growth and the between-personal factors that are associated with
      individual differences in the pattern of growth. RESULTS: The developmental speed
      of children with DS was found to be slower than that of typical children in all
      the three developmental domains assessed (i.e., the estimated coefficient of the
      slope for chronological age on DA was less than 1). DS Girls developed
      significantly faster than boys in non-verbal cognitive and language abilities.
      Low birth weight and CHD had a significant negative impact on development of non
      verbal cognitive abilities for boys, but had a somewhat positive effect for
      girls. CONCLUSION: As was shown in previous studies, the result of this study
      indicated that the children with DS develop slower than non-disabled children.
      Low birth weight and CHD were found to influence developmental trend of children
      with DS, differently for boys and girls.

PMID- 29054334
TI  - Is vatiquinone truly beneficial for Leigh syndrome?

PMID- 29054335
TI  - The relation between HbA1c and hypoglycemia revisited; a secondary analysis from
      an intervention trial in patients with type 1 diabetes and impaired awareness of
      hypoglycemia.
AB  - AIMS: We aimed to re-assess the previously shown but recently disputed
      association between HbA1c and severe hypoglycemia. METHODS: 52 Patients with T1D
      and IAH participated in an earlier reported randomized, crossover trial with two
      16-week intervention periods comparing continuous glucose monitoring (CGM) with
      self-monitoring of blood glucose (SMBG). In this previous study, time spent in
      normoglycemia (the primary outcome), was improved by 9.6% (p<0.0001). We
      performed post-hoc analyses using a zero-inflated Poisson regression model to
      assess the relationship between severe hypoglycemia and HbA1c, glucose
      variability and duration of diabetes. RESULTS: During SMBG use, HbA1c and the
      number of severe hypoglycemic events were negatively associated (OR 0.20 [95% CI
      0.09 to 0.44]). During CGM use, this relationship showed an odds ratio of 0.65
      (95% CI 0.42 to 1.01). There was no significant relationship between glucose
      variability or duration of diabetes and severe hypoglycemia. CONCLUSIONS: In
      patients with T1D and IAH, treated with standard SMBG, a negative association
      exists between HbA1c and the number of severe hypoglycemic events. Thus, reaching
      target HbA1c values still comes with a higher risk of severe hypoglycemia. CGM
      weakens this association, suggesting CGM enables patients to reach their target
      HbA1c more safely.

PMID- 29054336
TI  - Network Design and the Brain.
AB  - Neural circuits have evolved to accommodate similar information processing
      challenges as those faced by engineered systems. Here, we compare neural versus
      engineering strategies for constructing networks. During circuit development,
      synapses are overproduced and then pruned back over time, whereas in engineered
      networks, connections are initially sparse and are then added over time. We
      provide a computational perspective on these two different approaches, including
      discussion of how and why they are used, insights that one can provide the other,
      and areas for future joint investigation. By thinking algorithmically about the
      goals, constraints, and optimization principles used by neural circuits, we can
      develop brain-derived strategies for enhancing network design, while also
      stimulating experimental hypotheses about circuit development and function.

PMID- 29054337
TI  - Dental pulp stem cells (DPSCs) increase prostate cancer cell proliferation and
      migration under in vitro conditions.
AB  - Cancer as a multistep and complicated disease is regulated by several molecular
      and cellular events. Cancer treatment could be managed at the early stages when
      the tumor is confined in the tissue. However, disseminated cancer cells
      metastasize to other body parts and generate new tumors resulting in mortality.
      Mesenchymal stem cells (MSCs) are found in different body parts and helps adult
      tissue regeneration. The role of MSCs in cancer progression has emerged as one of
      the important aspects in cancer biology and is the aim of interest in recent
      years. In the current study, effects of Dental Pulp Stem Cells (DPSCs) on PC-3
      prostate cancer cell proliferation and migration were conducted by cell
      proliferation, apoptosis, gene expression and cell migration analysis in vitro.
      Condition medium (CM) obtained from DPSCs increased cell proliferation of PC-3
      cells and decreased apoptosis. Either administration of CM or trans well co
      culture of DPSCs increased cell migration in scratch assay, confirmed by gene
      expression analysis of migratory genes including fibronectin, laminin and
      collagen type I (Col I). Furthermore, DPSCs participated in a self-organized
      structure with PC-3 cells in co-culture conditions. Overall, results indicated
      that DPSCs could promote PC-3 cancer cell proliferation and metastasis in co
      culture conditions in vitro.

PMID- 29054338
TI  - Non-contact and through-clothing measurement of the heart rate using ultrasound
      vibrocardiography.
AB  - We present a novel non-contact system for monitoring the heart rate on human
      subjects with clothes. Our approach is based on vibrocardiography, and measures
      locally skin displacements. Vibrocardiography with a laser Doppler vibrometer
      already allows monitoring of this vital sign, but can only be used on bare skin
      and requires an expensive piece of equipment. We propose here to use an airborne
      pulse-Doppler ultrasound system operating in the 20-60 kHz range, and comprised
      of an emitter focusing the ultrasound pulses on skin and a microphone recording
      the reflected waves. Our implementation was validated in vitro and on two healthy
      human subjects, using simultaneously laser vibrocardiography and
      electrocardiography as references. Accurate measurements of the heart rate on
      clothed skin suggest that our non-contact ultrasonic method could be implemented
      both inside and outside the clinical environment, and therefore benefit both
      medical and safety applications.

PMID- 29054339
TI  - Force estimation in fatigue condition using a muscle-twitch model during
      isometric finger contraction.
AB  - We propose a force estimation method in fatigue condition using a muscle-twitch
      model and surface electromyography (sEMG). The twitch model, which is an estimate
      of force by a single spike, was obtained from sEMG features and measured forces.
      Nine healthy subjects performed isometric index finger abduction until exhaustion
      for a series of dynamic contractions (0-20% MVC) to characterize the twitch model
      and static contractions (50% MVC) to induce muscle fatigue. Muscle fatigue was
      identified based on the changes of twitch model; the twitch peak decreased and
      the contraction time increased as muscle fatigue developed. Force estimation
      performance in non-fatigue and fatigue conditions was evaluated and its results
      were compared with that of a conventional method using the mean absolute value
      (MAV). In non-fatigue conditions, the performance of the proposed method (0.90 +/
      0.05) and the MAV method (0.88 +/- 0.06) were comparable. In fatigue conditions,
      the performance was significantly improved for the proposed method (0.87 +/-
      0.05) compared with the MAV (0.78 +/- 0.09).

PMID- 29054340
TI  - The Transmission of Family Food and Mealtime Practices From Adolescence to
      Adulthood: Longitudinal Findings From Project EAT-IV.
AB  - OBJECTIVE: To determine whether family food and mealtime practices experienced in
      adolescence are carried forward into parenthood. DESIGN: Baseline (Project Eating
      and Activity in Teens and Young Adults [EAT]-I) and 15-year follow-up (EAT-IV)
      survey data from a population-based cohort study (Project EAT). PARTICIPANTS:
      Cohort members identified as parents at follow-up (n = 727). To gain additional
      data about the practices of both parents in the household, significant others
      completed surveys at EAT-IV (n = 380). MAIN OUTCOME MEASURE: Frequency of family
      meals, healthfulness of foods at home, frequency of meals in front of the
      television, and expectations of being home for dinner. ANALYSIS: Linear
      regression models tested associations between parent food and mealtime practices
      reported at baseline and follow-up controlling for demographics. RESULTS: Healthy
      and unhealthy home food availability, expectations to be home for dinner, and
      eating in front of the television in adolescence predicted similar outcomes 15
      years later among female parents (effect sizes range: beta = .2-.3; P < .001),
      and to a lesser extent among males. Families ate more frequent family meals when
      either 1 or both parents reported frequent family meals as an adolescent compared
      with when neither parent reported frequent family meals as an adolescent.
      CONCLUSIONS AND IMPLICATIONS: It is important to invest in parenting
      interventions that target healthful family food and mealtime practices because of
      the potential long-term impact on their own children's parenting practices.

PMID- 29054341
TI  - Clinical Potential of Prefusion RSV F-specific Antibodies.
AB  - Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory
      tract infections in the very young. The RSV fusion protein (F) is essential for
      virus entry because it mediates viral and host membrane fusion. During this
      fusion process F is converted from a metastable prefusion conformation into an
      energetically favored postfusion state. Antibodies that target F can prevent
      viral entry and reduce disease caused by RSV. During recent years, many prefusion
      F-specific antibodies have been described. These antibodies typically have
      stronger RSV-neutralizing activity compared to those that also bind F in the
      postfusion conformation. Here, we describe how F-specific antibodies protect
      against RSV and why specifically targeting prefusion F could have great clinical
      potential.

PMID- 29054342
TI  - Timing of hospital admission in labour: latent versus active phase, mode of birth
      and intrapartum interventions. A correlational study.
AB  - BACKGROUND: Hospitalization of women in latent labour often leads to a cascade of
      unnecessary intrapartum interventions, to avoid potential disadvantages the
      recommendation should be to stay at home to improve women's experience and
      perinatal outcomes. AIM: The primary aim of this study was to investigate the
      association between hospital admission diagnosis (latent vs active phase) and
      mode of birth. The secondary aim was to explore the relationship between hospital
      admission diagnosis, intrapartum intervention rates and maternal/neonatal
      outcomes. METHODS: A correlational study was conducted in a large Italian
      maternity hospital. Data from January 2013 to December 2014 were collected from
      the hospital electronic records. 1.446 records of low risk women were selected.
      These were dichotomized into two groups based on admission diagnosis: 'latent
      phase' or 'active phase' of labour. FINDINGS: 52.7% of women were admitted in
      active labour and 47.3% in the latent phase. Women in the latent phase group were
      more likely to experience a caesarean section or an instrumental birth,
      artificial rupture of membranes, oxytocin augmentation and epidural analgesia.
      Admission in the latent phase was associated with higher intrapartum
      interventions, which were statistically correlated to the mode of birth.
      CONCLUSIONS: Women admitted in the latent phase were more likely to experience
      intrapartum interventions, which increase the probability of caesarean section.
      Maternity services should be organized around women and families needs, providing
      early labour support, to enable women to feel reassured facilitating their
      admission in labour to avoid the cascade of intrapartum interventions which
      increases the risk of caesarean section.

PMID- 29054343
TI  - Aster yomena extract ameliorates pro-inflammatory immune response by suppressing
      NF-kappaB activation in RAW 264.7 cells.
AB  - BACKGROUND: Aster yomena, an edible vegetable, is a perennial herb found in
      Korea, China, Japan, and Siberia. It is used as folk medicine to treat cough,
      bronchial asthma, and insect bites. A. yomena was recently shown to have
      antioxidant and anti-asthmatic activities. Studies have not yet evaluated the
      anti-inflammatory effects of the various solvent fractions of A. yomena. We
      investigated the anti-inflammatory activity of various solvent fractions (hexane,
      dichloromethane, ethyl acetate, and butanol) from ethanol extract of A. yomena in
      activated macrophages. METHODS: Anti-inflammatory effects of A. yomena were
      investigated to determine the inhibitory effects of A. yomena against
      inflammation using RAW 264.7 mouse macrophages. To measure the effects of A.
      yomena on inflammatory mediators and cytokines, we used the following methods:
      cell viability assay, flow cytometry assay, ELISA assay, real-time PCR and
      western blotting. RESULTS: The dichloromethane fraction exhibited marked anti
      inflammatory activities by inhibiting nitric oxide (NO) and prostaglandin E2
      production and mRNA expression of inducible isoforms of NO synthase,
      cyclooxygenase-2, and cytokines (tumor necrosis factor alpha, interleukin (IL)-6,
      IL-1beta) in response to lipopolysaccharide (LPS) stimulation. Moreover,
      dichloromethane fraction from A. yomena significantly inhibited the
      transactivation of nuclear factor (NF)-kappaB and the nuclear translocation of
      the NF-kappaB p50 and p65 subunits. CONCLUSION: These results suggest that A.
      yomena may have anti-inflammatory activity in vitro, suggesting this herb could
      be a source of natural anti-inflammatory agents.

PMID- 29054344
TI  - Historical insights on growth rates of the reef-building corals Pavona gigantea
      and Porites panamensis from the Northeastern tropical Pacific.
AB  - Historical coral growth assessed by sclerochronology records provides an
      environmental retrospective and future perspective on the maintenance of coral
      reef ecosystems. Three growth parameters, extension rate, skeletal density, and
      calcification rate were evaluated over the past two decade's interval (1988-2013)
      in different gender of two massive corals Pavona gigantea and Porites panamensis.
      The species P. gigantea calcified two-times faster (0.84 +/- 0.29 g cm-2 yr-1)
      than P. panamensis (0.36 +/- 0.15 g cm-2 yr-1); and male colonies presents13-58%
      higher calcification rates than females. Annual growth parameters do not show
      significant trends over the period 1988-2013, but significant, growth disruption
      associated with ENSO events. The data presented here suggest that P.gigantea and
      P.panamensis from the area have developed phenotypic plasticity to a wide range
      of environmental condition; the life history of both species is reflected in
      their calcification rates during both optimal and non-optimal conditions over the
      last two decades. Massive species develop denser structures that provide a
      permanent habitat to many marine species and contributes to the long-term
      maintenance of coral reef communities in the eastern tropical Pacific.

PMID- 29054345
TI  - The Effect of Formal Robotic Residency Training on the Adoption of Minimally
      Invasive Surgery by Young Colorectal Surgeons.
AB  - OBJECTIVE: The minimally invasive approach to colorectal surgery is still
      underused. Only 50% to 60% of colectomies and 10% to 20% of rectal resections for
      cancer are performed laparoscopically. The increasing adoption of the robotic
      platform for colorectal surgery warrants re-evaluation of minimally invasive
      surgery (MIS) training techniques. Although considering lessons learned from past
      laparoscopic training, a standardized national robotic training program for colon
      and rectal surgery residents was developed and implemented in 2011. The objective
      of this study was to assess the effect of this program on the usage of MIS in
      practice following residency training. DESIGN: An internet-based 18 question
      survey was sent to all colon and rectal surgeons who graduated from ACGME
      approved colon and rectal surgery residencies from 2013 to 2016. The survey
      questions were designed to determine MIS practice patterns for young colon and
      rectal surgeons after residency training for those who participated in the
      standardized national robotics training course when compared to those who did not
      participate. Grouped bar charts with error bars are presented along with summary
      statistics to offer a descriptive overview of training experiences by cohort.
      SETTING/PARTICIPANTS: This study is a survey of colon and rectal surgeons who
      completed colon and rectal surgery residencies to include all 52 programs across
      the United States. RESULTS: The overall survey response rate was 37.2% (109 of
      293). Most (79.8%) of the colon and rectal surgery resident respondents
      participated in the formal robotic training course. The average respondent
      reported that 84% of colectomy cases and 74.8% of rectal resections done after
      residency training by all respondents were by the MIS approach. The laparoscopic
      approach was most prevalent for colectomies for both course participants
      (laparoscopic 55.1%, hand assisted lap 14.5%, and robotic 15.7%) and
      nonparticipants (laparoscopic 53.8%, hand assisted lap 12.3%, and robotic 15.9%).
      For rectal resections, the robotic approach was the preferred option for course
      participants (laparoscopic 24.5%, hand assist lap 14.0%, and robotic 39.2%)
      whereas laparoscopic and open approaches were used more often by nonparticipants
      (laparoscopic 36.8%, hand assist lap 8.0%, robotic 26.8%, and open 28.4%).
      Barriers to robotic implementation included lack of robotic mentors, inadequate
      robotic assistance, and the preference for the laparoscopic approach. CONCLUSION:
      The usage of MIS by young recently fellowship-trained colorectal surgeons is
      higher than previously reported. The proportion of rectal cases done robotically
      is higher compared to colon cases and with an apparent decrease in open rather
      than laparoscopic surgery, suggesting selective usage of robotic surgery for more
      challenging cases in the pelvis. Methods to more effectively increase the usage
      of minimally invasive approaches in colorectal surgery warrant further
      evaluation.

PMID- 29054346
TI  - Mixed-Ploidy Species: Progress and Opportunities in Polyploid Research.
AB  - Mixed-ploidy species harbor a unique form of genomic and phenotypic variation
      that influences ecological interactions, facilitates genetic divergence, and
      offers insights into the mechanisms of polyploid evolution. However, there have
      been few attempts to synthesize this literature. We review here research on the
      cytotype distribution, diversity, and dynamics of intensively studied mixed
      ploidy species and consider the implications for understanding mechanisms of
      polyploidization such as cytotype formation, establishment, coexistence, and post
      polyploid divergence. In general, mixed-ploidy species are unevenly represented
      among families: they exhibit high cytotype diversity, often within populations,
      and frequently comprise rare and odd-numbered ploidies. Odd-ploidies often occur
      in association with asexuality. We highlight research hypotheses and
      opportunities that take advantage of the unique properties of ploidy variation.

PMID- 29054347
TI  - Defining the "Frequent Exacerbator" Phenotype in COPD: A Hypothesis-Free
      Approach.
AB  - BACKGROUND: The COPD "frequent exacerbator" phenotype is usually defined by at
      least two treated exacerbations per year and is associated with a huge impact on
      patient health. However, existence of this phenotype and corresponding thresholds
      still need to be formally confirmed by statistical methods analyzing exacerbation
      profiles with no specific a priori hypothesis. The aim of this study was to
      confirm the existence of the frequent exacerbator phenotype with an innovative
      unbiased statistical analysis of prospectively recorded exacerbations. METHODS:
      Data from patients with COPD from the French cohort in Exacerbations of COPD
      Patients (EXACO) were analyzed using the KmL method designed to cluster
      longitudinal data and receiver operating characteristic (ROC) curve analysis to
      determine the best threshold to allocate patients to identified clusters.
      Univariate and multivariate analyses were performed to study characteristics
      associated with different clusters. RESULTS: Two clusters of patients were
      identified based on exacerbation frequency over time, with 2.89 exacerbations per
      year on average in the first cluster (n = 348) and 0.71 on average in the second
      cluster (n = 116). The best threshold to distinguish these clusters was two
      moderate to severe exacerbations per year. Frequent exacerbators had more airflow
      limitation, symptoms, and health-related quality of life impairment. A simple
      clinical score was derived to help identify patients at risk of exacerbations.
      CONCLUSIONS: These analyses confirmed the existence and clinical relevance of a
      frequent exacerbator subgroup of patients with COPD and the currently used
      threshold to define this phenotype.

PMID- 29054348
TI  - Survival of Lung Transplant Candidates With COPD: BODE Score Reconsidered.
AB  - BACKGROUND: The BMI, obstruction, dyspnea, and exercise capacity (BODE) score is
      used to inform prognostic considerations for lung transplantation for COPD, but
      it has not been validated in this context. A large proportion of mortality in
      COPD is attributable to comorbidities that could preclude transplant candidacy.
      We hypothesized that patients with COPD who are selected as transplant candidates
      experience better survival than traditional interpretation of BODE scores might
      indicate. METHODS: We performed a retrospective analysis of survival according to
      the BODE score for patients with COPD in the United Network of Organ Sharing
      (UNOS) database of lung transplantation candidates (n = 4,377) compared with the
      cohort of patients with COPD in which the BODE score was validated (n = 625).
      RESULTS: Median survival in the fourth quartile of BODE score was 59 months (95%
      CI, 51-77 months) in the UNOS cohort and 37 months (95% CI, 29-42 months) in the
      BODE validation cohort. In models controlling for BODE score and incorporating
      lung transplantation as a competing end point, the risk of death was higher in
      the BODE validation cohort (subhazard ratio, 4.8; 95% CI, 4.0-5.7; P < .001). The
      risk difference was greatest in the fourth quartile of BODE scores (SHR, 6.1; 95%
      CI, 4.9-7.6; P < .001). CONCLUSIONS: Extrapolation of prognosis based on the BODE
      score overestimates mortality risk in lung transplantation candidates with COPD.
      This is likely due to a lower prevalence of comorbid conditions attributable to
      the lung transplantation evaluation screening process.

PMID- 29054349
TI  - Peripheral markers of inflammation, oxidative & nitrosative stress pathways and
      memory functions as a new target of pharmacotherapy in depression.

PMID- 29054351
TI  - Frequency of Bone Health Presentations at National Hand Meetings.
AB  - PURPOSE: The purpose of this study was to determine the frequency with which
      osteoporosis topics (screening, medical treatment, and fracture prevention) are
      presented at national hand surgery meetings. This was compared with the frequency
      of the same topics presented at the Orthopaedic Trauma Association (OTA) annual
      meetings. METHODS: The annual meeting programs for the American Society for
      Surgery of the Hand (ASSH), the American Association for Hand Surgery (AAHS), and
      the OTA from the previous 10 years (2007-2016) were searched for presentations
      that covered bone health at each of these meetings. We categorized the
      presentations as either instructional or research. RESULTS: There were 2 bone
      health instructional presentations at hand surgery meetings in contrast to 13
      presentations at OTA meetings over the last 10 years. For the last 9 years, the
      OTA has featured at least 1 instructional presentation on bone health every year.
      We identified 11 research presentations at the hand surgery meetings compared
      with 16 at the OTA meetings. CONCLUSIONS: Osteoporosis and bone health are
      infrequently presented instructional topics at national hand meetings compared
      with OTA meetings. The cause of the difference is unclear and likely
      multifactorial, varying each year with different program chairs and committees.
      The level of involvement of hand surgeons in osteoporosis management is
      controversial; however, incorporation of this topic may stimulate discussion and
      help identify solutions for this controversy. CLINICAL RELEVANCE: It may benefit
      hand surgeons to place more importance on osteoporosis screening and treatment.
      We believe that there should be an annual instructional course on this topic at
      the ASSH and AAHS meetings.

PMID- 29054352
TI  - Patient-Related Risk Factors for Infection Following Open Carpal Tunnel Release:
      An Analysis of Over 450,000 Medicare Patients.
AB  - PURPOSE: To establish the rate of postoperative infection after open carpal
      tunnel release (CTR) on a national level using an administrative database and
      define relevant patient-related risk factors associated with its occurrence.
      METHODS: The PearlDiver patient records database was used to query the 100%
      Medicare Standard Analytic Files retrospectively from 2005 to 2012 for patients
      undergoing open CTR using Current Procedural Terminology code 64721.
      Postoperative infection within 90 days of surgery was assessed using both
      International Classification of Diseases, Ninth Revision codes for diagnoses of
      postoperative infection or pyogenic arthritis of the wrist and Current Procedural
      Terminology codes for procedures for these indications, including either open or
      arthroscopic irrigation and debridement. We used a multivariable binomial
      logistic regression model that allows for assessment of the independent effect of
      a variable while controlling for remaining variables to evaluate which patient
      demographics and medical comorbidities were associated with an increased risk for
      postoperative infection. Adjusted odds ratios and 95% confidence intervals were
      calculated for each risk factor, with P < .05 considered statistically
      significant. RESULTS: A total of 454,987 patients met all inclusion and exclusion
      criteria. Of these patients, 1,466 developed a postoperative infection,
      corresponding to an infection rate of 0.32%. Independent positive risk factors
      for infection included younger age, male sex, obesity (body mass index of 30 to
      40), morbid obesity (body mass index greater than 40), tobacco use, alcohol use,
      and numerous medical comorbidities including diabetes, inflammatory arthritis,
      peripheral vascular disease, chronic liver disease, chronic kidney disease,
      chronic lung disease, and depression. CONCLUSIONS: The current study reinforced
      conventional wisdom regarding the the overall low infection rate after CTR and
      revealed numerous patient-related risk factors that are independently associated
      with an increased risk of infection after open CTR in patients enrolled in
      Medicare. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 29054353
TI  - The Rate of Radial Head Prosthesis Removal or Revision: A Systematic Review and
      Meta-Analysis.
AB  - PURPOSE: We conducted a meta-analysis and systematic review with the primary
      objective to determine the overall incidence of radial head prosthesis removal or
      revision. Our secondary objectives addressed the incidence of removal or revision
      based on the type of prosthesis fixation (cemented, uncemented smooth stem,
      uncemented press-fit), material (metal, Vitallium, titanium, pyrocarbon), and
      design (short vs long stem and monopolar vs bipolar), and the reasons for
      prosthetic removal or revision. METHODS: We included 30 studies with a total of
      1,017 patients out of whom 77 prostheses were removed and 45 prostheses were
      revised. RESULTS: The pooled rate of radial head prosthesis removal or revision
      was 10.0% (95% confidence interval, 7.3%-13.6%) with a mean follow-up of 38
      months. Subgroup analysis showed that the incidence of removal/revision was
      lowest with the cemented fixation, longer-stem, Vitallium material, and bipolar
      prosthesis. More than half of the prostheses were removed/revised for excision of
      the heterotopic ossification (47%) and for the treatment of stiffness and
      limitation of motion (42%). Other reasons recorded were pain (19%), loosening
      (16%), overstuffing (13%), instability (12%), infection (8%), and prosthesis
      disassembly (4%). CONCLUSIONS: The current data show that the highest incidence
      of removal/revision occurred within 2 years after implantation. There was no
      major difference in the incidence of removal/revision among different designs and
      materials. Implant removal was often performed as part of a procedure to manage
      elbow stiffness and heterotopic ossification at the surgeon's preference, not
      necessarily because the implant was malfunctioning. It appears that most radial
      head arthroplasties have an acceptable and comparable mid-term longevity;
      however, it is unclear whether long-term longevity will differ between devices.
      TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 29054354
TI  - Strategies to Reduce Ischemia Reperfusion Injury in Vascularized Composite
      Allotransplantation of the Limb.
AB  - An important and often underinvestigated contributor to solid organ transplant
      rejection is ischemia reperfusion injury. This pathophysiological response
      releases damaging reactive oxygen species and cell stress signals that initiate
      inflammation, which has a critical role in priming the immune system for
      allorecognition. In time, this renders graft dysfunction and how this response is
      mediated in composite tissues remains unknown. Current protocols are drawn from
      solid organ transplantation with little scientific basis as to how this informs
      current hand transplantation practices. In addition to preservation flush and
      allograft cooling, machine perfusion is placing itself experimentally as a
      concept that could act to promote viability and increase the critical ischemic
      window, which is especially beneficial at a time of limited donors. With the
      increasing prevalence worldwide of hand transplantation, we review the potential
      contribution of ischemia reperfusion injury to hand allograft rejection including
      both current and experimental strategies.

PMID- 29054350
TI  - What can we learn from ineffective erythropoiesis in thalassemia?
AB  - Erythropoiesis is a dynamic process regulated at multiple levels to balance
      proliferation, differentiation and survival of erythroid progenitors. Ineffective
      erythropoiesis is a key feature of various diseases, including beta-thalassemia.
      The pathogenic mechanisms leading to ineffective erythropoiesis are complex and
      still not fully understood. Altered survival and decreased differentiation of
      erythroid progenitors are both critical processes contributing to reduced
      production of mature red blood cells. Recent studies have identified novel
      important players and provided major advances in the development of targeted
      therapeutic approaches. In this review, beta-thalassemia is used as a
      paradigmatic example to describe our current knowledge on the mechanisms leading
      to ineffective erythropoiesis and novel treatments that may have the potential to
      improve the clinical phenotype of associated diseases in the future.

PMID- 29054355
TI  - The Effect of Bisphosphonates on the Clinical and Radiographic Outcomes of Distal
      Radius Fractures in Women.
AB  - PURPOSE: To compare clinical and radiographic outcomes of distal radius fractures
      (DRF) treated with nonsurgical management in female postmenopausal patients
      receiving bisphosphonate (BP) therapy at the time of injury with those not
      receiving BP therapy. METHODS: We prospectively enrolled 33 female postmenopausal
      patients with 35 DRF between December 2010 and January 2014 at 2 Level I tertiary
      care centers. Eleven patients with 12 DRF were currently receiving BP at the time
      of injury (BP group) and were compared with 22 controls with 23 DRF (CONT group)
      who were not receiving BP at the time of injury. All were postmenopausal women
      with fragility fractures managed nonsurgically. Primary outcomes were
      radiographic healing measured by the Radius Union Scoring System (RUSS) score and
      clinical and functional outcomes. Radiographs, range of motion, pinch and grip
      strength, Patient-Rated Wrist Evaluation scores, and Disability of the Arm,
      Shoulder, and Hand scores were determined at 6, 9, and 12 weeks and 1 year from
      time of injury and compared between groups. RESULTS: The BP and CONT groups were
      similar in terms of age, comorbidities, and fracture severity. Both groups had
      progressively improving RUSS scores from the time of injury throughout subsequent
      evaluation, and all patients achieved radiographic union. Fracture healing was
      similar in both groups at 6, 9, and 12 weeks after injury. The RUSS scores were
      slightly better in the CONT group at 1 year. There were no differences in wrist
      range of motion, pinch, grip, Patient-Rated Wrist Evaluation, or Disability of
      the Arm, Shoulder, and Hand scores at any time point after injury. CONCLUSIONS:
      Patients receiving BP at the time of DRF had clinical outcomes similar to those
      not receiving antiresorptive treatment. Although there was a small difference in
      RUSS scores at 1 year after injury, this was not clinically relevant and all
      fractures united in a similar time frame with no healing complications. These
      results suggest that BP may be continued throughout nonsurgical management of DRF
      without detrimental effects on healing or function. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic II.

PMID- 29054356
TI  - Enzyme prodrug therapies and therapeutic enzymes.

PMID- 29054357
TI  - Stem cells and heart disease - Brake or accelerator?
AB  - After two decades of intensive research and attempts of clinical translation,
      stem cell based therapies for cardiac diseases are not getting closer to clinical
      success. This review tries to unravel the obstacles and focuses on underlying
      mechanisms as the target for regenerative therapies. At present, the principal
      outcome in clinical therapy does not reflect experimental evidence. It seems that
      the scientific obstacle is a lack of integration of knowledge from tissue repair
      and disease mechanisms. Recent insights from clinical trials delineate mechanisms
      of stem cell dysfunction and gene defects in repair mechanisms as cause of
      atherosclerosis and heart disease. These findings require a redirection of
      current practice of stem cell therapy and a reset using more detailed analysis of
      stem cell function interfering with disease mechanisms. To accelerate scientific
      development the authors suggest intensifying unified computational data analysis
      and shared data knowledge by using open-access data platforms.

PMID- 29054358
TI  - A comparative study of warheads for design of cysteine protease inhibitors.
AB  - The effects on potency of cruzain inhibition of replacing a nitrile group with
      alternative warheads were explored. The oxime was almost an order of magnitude
      more potent than the corresponding nitrile and has the potential to provide
      access to the prime side of the catalytic site. Dipeptide aldehydes and
      azadipeptide nitriles were found to be two orders of magnitude more potent
      cruzain inhibitors than the corresponding dipeptide nitriles although potency
      differences were modulated by substitution at P1 and P3. Replacement of the alpha
      methylene of a dipeptide aldehyde with cyclopropane led to a loss of potency of
      almost three orders of magnitude. The vinyl esters and amides that were
      characterized as reversible inhibitors were less potent than the corresponding
      nitrile by between one and two orders of magnitude.

PMID- 29054359
TI  - Syntheses of conformationally restricted benzopyran based triarylethylenes as
      growth inhibitors of carcinoma cells.
AB  - A series of conformationally restricted benzopyran based triarylethylenes has
      been synthesized and characterized as potential growth inhibitors of breast
      carcinoma cells. The synthesized compounds (14a-b, 15a and 16a-e) presented
      significant growth inhibition of ER+ and ER- breast cancer cells within the range
      of IC50 0.55-9.96uM. Amongst other, 16c showed potent anticancer activity at IC50
      0.95uM in MCF-7 cells with good selectivity (Selectivity Index 4.47) towards
      healthy cells. The mechanistic studies for 16c were performed to elucidate
      possible mode of action which showed 16c elicited anticancer activity through
      necroptosis process.

PMID- 29054360
TI  - Enhanced radical scavenging activity of a procyanidin B3 analogue comprised of a
      dimer of planar catechin.
AB  - Proanthocyanidins are oligomers of catechins that exhibit potent antioxidative
      activity and inhibit binding of oxidized low-density lipoprotein (OxLDL) to the
      lectin-like oxidized LDL receptor (LOX-1), which is involved in the onset and
      development of arteriosclerosis. Previous attempts aimed at developing
      proanthocyanidin derivatives with more potent antioxidative activity and stronger
      inhibition for LOX-1 demonstrated the synthesis of a novel proanthocyanidin
      derivative (1), in which the geometry of one catechin molecule in procyanidin B3
      was constrained to a planar orientation. The radical scavenging activity of 1 was
      1.9-fold higher than that of procyanidin B3. Herein, we synthesized another
      procyanidin B3 analogue (2), in which the geometries of both catechin molecules
      in the dimer were constrained to planar orientations. The radical scavenging
      activity of 2 was 1.5-fold higher than that of 1, suggesting that 2 may be a more
      effective candidate than 1 as a therapeutic agent to reduce oxidative stress
      induced in arteriosclerosis or related cerebrovascular disease.

PMID- 29054362
TI  - Red blood cell transfusion in infants and children - Current perspectives.
AB  - Children routinely receive packed red blood transfusion when they are admitted in
      the intensive care unit or undergoing cardiac surgeries. These guidelines aim to
      summarize literature and provide transfusion triggers exclusively in infants and
      children.

PMID- 29054361
TI  - Metastatic melanoma imaging using a novel Tc-99m-labeled lactam-cyclized alpha
      MSH peptide.
AB  - The purpose of this study was to determine the metastatic melanoma imaging
      property of 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex {hydrazinonicotinamide-8
      aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH2}. HYNIC-Aoc-Nle
      CycMSHhex was synthesized using fluorenylmethyloxy carbonyl (Fmoc) chemistry. The
      IC50 value of HYNIC-Aoc-Nle-CycMSHhex was 0.78 +/- 0.13 nM for B16/F10 melanoma
      cells. 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex displayed significantly higher uptake
      (14.26 +/- 2.74 and 10.45 +/- 2.31% ID/g) in B16/F10 metastatic melanoma-bearing
      lung than that in normal lung (0.90 +/- 0.15 and 0.53 +/- 0.14% ID/g) at 2 and 4
      h post-injection, respectively. B16/F10 pulmonary metastatic melanoma lesions
      were clearly visualized by SPECT/CT using 99mTc(EDDA)-HYNIC-Aoc-Nle-CycMSHhex as
      an imaging probe at 2 h post-injection, underscoring its potential as an imaging
      probe for metastatic melanoma detection.

PMID- 29054363
TI  - Role of Zc3h12a in enhanced IL-6 production by newborn mononuclear cells in
      response to lipopolysaccharide.
AB  - BACKGROUND: The uncontrolled inflammatory response following infection is closely
      related to the morbidity and mortality of neonates. Interleukin 6 (IL-6) plays an
      important role in the pathogenesis and prognosis of this process. To better
      elucidate the secretion of IL-6 following infection in neonates, we investigated
      the IL-6 level and mechanism of IL-6/TLR4 signaling pathways. METHODS: We
      compared the IL-6, procalcitonin (PCT), and CRP levels between septic neonates
      and toddlers. In vitro cord blood samples from healthy term neonates and
      peripheral venous blood from healthy adult volunteers were collected. Protein
      expression was analyzed by Western blotting, mRNA expression by real-time PCR and
      membrane molecule expression by flow cytometry. RESULTS: The IL-6 concentrations
      were significantly higher in the neonate group than in the toddler group (p <
      0.05). In the toddler group, the IL-6 concentrations were correlated positively
      with both PCT and CRP (PCT: r = 0.451, p = 0.001; CRP: r = 0.243, p = 0.023). In
      vitro, the secretion of IL-6 increased with the rising concentrations of LPS; at
      1000 ng/ml LPS, IL-6 secretion from the monocytes of neonates was significantly
      higher than that of adults. There was a marked decreased level of MyD88 in
      neonate monocytes compared with that in adult monocytes. Additionally, the mRNA
      levels of Zc3h12a in neonate monocytes were significantly lower than those in
      adult monocytes following LPS stimulation. CONCLUSION: Neonates displayed
      enhanced IL-6 production after infection. Our study, for the first time, reported
      a significant decrease in the expression of Zc3h12a in neonates. Thus, Zc3h12a
      may be a key factor for the aberrant increase in IL-6 after neonate infection.

PMID- 29054364
TI  - [Indication for mitral valve interventions: Development of a quality indicator
      for external hospital quality assurance].
AB  - BACKGROUND: The indication for a mitral valve intervention is an important
      patient-relevant parameter for the assessment of process quality and the
      comparison of healthcare providers. In this article, we describe the development
      of a corresponding quality indicator for an external hospital quality assurance
      (QA) procedure in Germany. METHODS: An expert panel was set up by the aQua
      Institute to assist with the development of a QA procedure for mitral valve
      interventions and the associated quality indicators. In a comprehensive,
      systematic literature and evidence research, the American and European guidelines
      were identified as the best evidence available. Especially the more current
      American guideline formed the basis on which a quality indicator dealing with the
      correct indication for a mitral valve intervention was developed. RESULTS: The
      developed quality indicator assesses the proportion of patients for whom an
      indication for a mitral valve intervention was determined in compliance with
      guideline recommendations. The indicator differentiates between surgical and
      catheter-based procedures. To determine whether or not the indication was
      correct, different medical parameters are included, such as, for example, type of
      mitral valve defect, etiology of the disease, severity of symptoms, valve
      morphology (e. g., mitral valve area), valve hemodynamics and comorbidity, which
      healthcare providers have to document. CONCLUSION: The documentation for the
      developed quality indicator is considerable. Nonetheless, its relevance is
      undeniable because it allows the user to determine whether a surgical or catheter
      based mitral valve intervention was necessary and performed according to
      guideline recommendations. In the first year of its implementation, this
      indicator should be evaluated for further improvement and simplification of
      assessment.

PMID- 29054365
TI  - Corrigendum to "Lateralization of resting state networks and relationship to age
      and gender" [NeuroImage 104 (2015) 310-325].

PMID- 29054366
TI  - Simvastatin accelerates hematoma resolution after intracerebral hemorrhage in a
      PPARgamma-dependent manner.
AB  - To date, the neuroprotective effects of statins on intracerebral hemorrhage (ICH)
      are not well established. This study explored the effect and potential mechanism
      of simvastatin treatment on ICH. In the present study, the effects of simvastatin
      on hematoma absorption, neurological outcome, CD36 expression and microglia
      polarization were examined in rat model of ICH model. In the meantime, inhibitory
      effect of PPARgamma inhibitor GW9662 was investigated following ICH.
      Additionally, the effect of simvastatin on PPARgamma activation was also
      investigated in rat ICH model and primary microglia culture. Much more, the role
      of PPARgamma and CD36 in simvastatin-mediated erythrocyte phagocytosis was also
      detected by using in vivo or in vitro phagocytosis models, respectively. After
      ICH, simvastatin promoted hematoma absorption and improved neurological outcome
      after ICH while upregulating CD36 expression and facilitating M2 phenotype
      polarization in perihematomal microglia. In addition, simvastatin increased
      PPARgamma activation and reinforced microglia-induced erythrocyte phagocytosis in
      vivo and in vitro. All above effects of simvastatin were abolished by PPARgamma
      inhibitor GW9662. In conclusion, our data suggested that simvastatin could
      enhance hematoma clearance and attenuate neurological deficits possibly by
      activating PPARgamma.

PMID- 29054367
TI  - Monoamine oxidase-B inhibitor protects degenerating spinal neurons, enhances
      nerve regeneration and functional recovery in sciatic nerve crush injury model.
AB  - Monoamine oxidase-B (MAOB), a flavin adenine dinucleotide (FAD), is an enzyme
      which catalyzes the oxidation of amines. MAOB is proposed to play a major role in
      the pathogenesis of neurodegeneration through the production of reactive oxygen
      species (ROS) and neurotoxins. The present study was designed to outline the
      effects of the MAOB inhibitor (MAOB-I) on neuroprotection of spinal neurons,
      regeneration of sciatic nerve fibers, and recovery of sensory-motor functions in
      the sciatic nerve crush injury model. Male Wistar rats (4-months-old) were
      assigned to i) Naive (N), ii) Sham (S), iii) Sciatic nerve crush and treated with
      saline (CRUSH + SALINE) and iv) Sciatic nerve crush and treated with MAOB
      inhibitor (CRUSH + MAOB-I) groups (n = 10/group). In groups iii and iv, the crush
      injury was produced by crushing the sciatic nerve followed by treatment with
      saline or MAOB-I (Selegiline(r) 2.5 mg/kg) intraperitoneally for 10 days.
      Behavioral tests were conducted from week 1 to week 6. At the end of the study,
      sciatic nerve and lumbar spinal cord were examined by immunohistochemistry, light
      and electron microscopy. MAOB-I treatment showed significant improvement in
      sensory and motor functions compared to saline treatment (p < 0.05-0.001) in
      injured nerves. The morphological study showed a significantly increased number
      of nerve fibers in sciatic nerve distal to the site of injury (p < 0.05), with
      better myelination pattern in CRUSH + MAOB-I treated group compared to CRUSH +
      SALINE group. Spinal cord ventral horns showed a significant increase in the
      number of NeuN-immunoreactive neurons in the MAOB-I treated group compared to
      Saline treated group (p < 0.01). MAOB-I has a significant potential for
      protecting the degenerating spinal cord neurons and enhancing the regeneration of
      injured sciatic nerve fibers following crush injury.

PMID- 29054368
TI  - An intermediate level of CD161 expression defines a novel activated,
      inflammatory, and pathogenic subset of CD8+ T cells involved in multiple
      sclerosis.
AB  - Several lines of evidence support a key role for CD8+ T cells in central nervous
      system tissue damage of patients with multiple sclerosis. However, the precise
      phenotype of the circulating CD8+ T cells that may be recruited from the
      peripheral blood to invade the CNS remains largely undefined to date. It has been
      suggested that IL-17 secreting CD8 (Tc17) T cells may be involved, and in humans
      these cells are characterized by the expression of CD161. We focused our study on
      a unique and recently described subset of CD8 T cells characterized by an
      intermediate expression of CD161 as its role in neuroinflammation has not been
      investigated to date. The frequency, phenotype, and function of CD8+ T cells with
      an intermediate CD161 expression level were characterized ex-vivo, in vitro, and
      in situ using RNAseq, RT-PCR, flow cytometry, TCR sequencing, and
      immunohistofluorescence of cells derived from healthy volunteers (n = 61), MS
      subjects (n = 90), as well as inflammatory (n = 15) and non-inflammatory controls
      (n = 6). We report here that CD8+CD161int T cells present characteristics of
      effector cells, up-regulate cell-adhesion molecules and have an increased ability
      to cross the blood-brain barrier and to secrete IL-17, IFNgamma, GM-CSF, and IL
      22. We further demonstrate that these cells are recruited and enriched in the CNS
      of MS subjects where they produce IL-17. In the peripheral blood, RNAseq, RT-PCR,
      high-throughput TCR repertoire analyses, and flow cytometry confirmed an
      increased effector and transmigration pattern of these cells in MS patients, with
      the presence of supernumerary clones compared to healthy controls. Our data
      demonstrate that intermediate levels of CD161 expression identifies activated and
      effector CD8+ T cells with pathogenic properties that are recruited to MS
      lesions. This suggests that CD161 may represent a biomarker and a valid target
      for the treatment of neuroinflammation.

PMID- 29054369
TI  - Exosome is a mechanism of intercellular drug transfer: Application of
      quantitative pharmacology.
AB  - PURPOSE: Exosomes are small membrane vesicles (30-100nm in diameter) secreted by
      cells into extracellular space. The present study evaluated the effect of
      chemotherapeutic agents on exosome production and/or release, and quantified the
      contribution of exosomes to intercellular drug transfer and pharmacodynamics.
      METHODS: Human cancer cells (breast MCF7, breast-to-lung metastatic LM2, ovarian
      A2780 and OVCAR4) were treated with paclitaxel (PTX, 2-1000nM) or doxorubicin
      (DOX, 20-1000nM) for 24-48h. Exosomes were isolated from the culture medium of
      drug-treated donor cells (Donor cells) using ultra-centrifugation, and analyzed
      for acetylcholinesterase activity, total proteins, drug concentrations, and
      biological effects (cytotoxicity and anti-migration) on drug-naive recipient
      cells (Recipient cells). These results were used to develop computational
      predictive quantitative pharmacology models. RESULTS: Cells in exponential growth
      phase released ~220 exosomes/cell in culture medium. PTX and DOX significantly
      promoted exosome production and/or release in a dose- and time-dependent manner,
      with greater effects in ovarian cancer cells than in breast cancer cells.
      Exosomes isolated from Donor cells contained appreciable drug levels (2
      7pmole/106 cells after 24h treatment with 100-1000nM PTX), and caused
      cytotoxicity and inhibited migration of Recipient cells. Quantitative
      pharmacology models that integrated cellular PTX pharmacokinetics with PTX
      pharmacodynamics successfully predicted effects of exosomes on intercellular drug
      transfer, cytotoxicity of PTX on Donor cells and cytotoxicity of PTX-containing
      exosomes on Recipient cells. Additional model simulations indicate that within
      clinically achievable PTX concentrations, the contribution of exosomes to active
      drug efflux increased with drug concentration and exceeded the p-glycoprotein
      efflux when the latter was saturated. CONCLUSIONS: Our results indicate (a)
      chemotherapeutic agents stimulate exosome production or release, and (b) exosome
      is a mechanism of intercellular drug transfer that contributes to
      pharmacodynamics of neighboring cells.

PMID- 29054370
TI  - Accessibility of axonal G protein coupled mu-opioid receptors requires conceptual
      changes of axonal membrane targeting for pain modulation.
AB  - The mechanisms of axonal trafficking and membrane targeting are well established
      for sodium channels, which are the principle targets for perineurally applied
      local anaesthetics. However, they have not been thoroughly investigated for G
      protein coupled receptors such as mu-opioid receptors (MOR). Focusing on these
      axonal mechanisms, we found that axonal MOR functionality is quite distinct in
      two different pain states, i.e. hindpaw inflammation and nerve injury. We
      observed axonal membrane MOR binding and functional G protein coupling
      exclusively at sites of CCI nerve injury. Moreover at these axonal membrane
      sites, MOR exhibited extensive co-localization with the membrane proteins SNAP
      and Na/K-ATPase as well as NGF-dependent enhanced lipid rafts and L1CAM anchoring
      proteins. Silencing endogenous L1CAM with intrathecal L1CAM specific siRNA,
      disrupting lipid rafts with the perineurial cholesterol-sequestering agent
      MbetaCD, as well as suppressing NGF receptor activation with the perineurial NGF
      receptor inhibitor K252a abrogated MOR axonal membrane integration, functional
      coupling, and agonist-elicited antinociception at sites of nerve injury. These
      findings suggest that local conceptual changes resulting from nerve injury are
      required for the establishment of functional axonal membrane MOR. Axonal
      integration and subsequent accessibility of functionally coupled MOR are of great
      relevance particularly for patients suffering from severe pain due to nerve
      injury or tumour infiltration.

PMID- 29054371
TI  - Ragweed pollen as an oral vaccine delivery system: Mechanistic insights.
AB  - We have recently developed pollen grains (PGs) as a unique method to deliver
      vaccines orally. Extensive chemical processing ensures allergen-free pollen
      microcapsules that can be loaded with vaccine antigens. Successful oral vaccine
      delivery has been previously demonstrated by us in a mouse model. However, the
      underlying mechanisms that help the processed PGs to achieve this goal were not
      fully understood. In this study, we wanted to understand the effects of
      chemically processed ragweed pollen (Ambrosia elatior) on the innate immune
      system. Intestinal epithelial cells, macrophages, and dendritic cells all bridge
      the innate and adaptive immunity. This study has shown that in response to
      ragweed pollen all these cells release inflammatory cytokines and chemokines.
      Scanning electron microscopy imaging revealed that macrophages can engulf ragweed
      pollen. In addition, in the presence of ragweed, mouse dendritic cells
      upregulated their activation markers, that is, CD40, CD80, CD86, and MHC class II
      molecules. Ragweed pollens did not cause significant cell membrane damage as
      compared to similarly sized poly (lactic-co-glycolic acid) particles. Moreover,
      ragweed did not affect the integrity of the intestinal epithelial cells. Ragweed
      pollens were also found in the subepithelial region of the small intestine 24h
      after pollens were gavaged to mice. Our current findings lead to the conclusion
      that besides transporting the vaccine cargo, ragweed pollen shells have
      additional immunomodulatory properties that help the orally delivered antigen to
      effectively induce an immune response.

PMID- 29054372
TI  - Simultaneously overcome tumor vascular endothelium and extracellular matrix
      barriers via a non-destructive size-controlled nanomedicine.
AB  - Tumor vascular endothelium and extracellular matrix (ECM) as the major barriers
      of anticancer nanomedicine greatly limited the anticancer efficacy of treatment,
      but few strategies were available to overcome them simultaneously. Thus, herein a
      strategy was presented to utilize reversible vasodilatation effect of nitric
      oxide (NO) and size-controlled characteristic of ultrasound responsive liposome
      (URL) to construct a non-destructive nanomedicine, which was able to cross both
      obstacles simultaneously. In this work, URL was built as a carrier via forming a
      gas layer between lipid bilayer to encapsulate small particles PAMAM@DOX (PD,
      ~10nm) and NO donation-nitrosoglutathione (GSNO). Under ultrasound (US)
      stimulation, GSNO fastly generated NO that acting on tumor vascular smooth
      muscle, resulting in tumor vascular vasodilatation, meanwhile the URL lipid
      bilayer was destroyed, leading to release sharply of small nanoparticles PD.
      Combination vasodilatory effect of NO and size-controlled characteristic of URL
      allowed vast drugs to extravasate through endothelial gap and penetrate into
      tumor deep. Upon different types of cancers vary greatly in vascular structure,
      two distinctly different tumor, MCF-7 human breast carcinoma and MiaPaCa-2 human
      pancreatic carcinoma, were chosen to test the anticancer efficacy of URL. As a
      result, URL-based nanosystem was significantly more effective than the
      conventional liposome (CL) in tumor treatment, particularly in much less leaky
      MiaPaCa-2 tumor treatment (tumor therapeutic efficiency of URL/PD/GSNO+US
      increased by 32.5% and 56.5% compared to CL/DOX in MCF-7 and MiaPaCa-2 tumor
      treatment). This study offers a new method to enhance tumor drug accumulation
      along with minimal toxicity for future clinical cancer treatments.

PMID- 29054373
TI  - From concept to in vivo testing: Microcontainers for oral drug delivery.
AB  - This work explores the potential of polymeric micrometer sized devices
      (microcontainers) as oral drug delivery systems (DDS). Arrays of detachable
      microcontainers (D-MCs) were fabricated on a sacrificial layer to improve the
      handling and facilitate the collection of individual D-MCs. A model drug,
      ketoprofen, was loaded into the microcontainers using supercritical CO2
      impregnation, followed by deposition of an enteric coating to protect the drug
      from the harsh gastric environment and to provide a fast release in the
      intestine. In vitro, in vivo and ex vivo studies were performed to assess the
      viability of the D-MCs as oral DDS. D-MCs improved the relative oral
      bioavailability by 180% within 4h, and increased the absorption rate by 2.4 times
      compared to the control. This work represents a significant step forward in the
      translation of these devices from laboratory to clinic.

PMID- 29054374
TI  - Comparative Analysis of Clinical Outcomes and Procedural Costs between the
      Conventional Two-stage Technique and 4D Brachytherapy for Early Prostate Cancer.
AB  - AIMS: To assess long-term outcomes and resource use of 4D Brachytherapy, a one
      stage real-time implant for the treatment of prostate cancer that uses stranded
      and loose iodine-125 seeds, and to compare with the conventional two-stage (2S)
      technique. MATERIALS AND METHODS: Prospectively collected data of men who
      underwent 2S and 4D low dose rate brachytherapy in a single institution were
      analysed. Survival estimates were analysed using the Kaplan-Meier method and Log
      rank test. Treatment failure rates were further compared by Cox proportional
      hazards (Coxph) regression or by a surrogate prostate-specific antigen value cut
      off of 0.4 ng/ml 48 months post-implant. Treatment toxicity outcomes were also
      evaluated. Comparative costs were based on published English National Health
      Service data. RESULTS: We compared outcomes of 690 men treated with 2S and 1031
      men with 4D brachytherapy. Median follow-up times were 10.4 and 5.2 years (P <
      0.001) for 2S and 4D cases, respectively. Day 0 post-implant dosimetry was
      improved in 4D brachytherapy patients. Five years post-implant >=98% of cases
      were alive and >=95% were free from disease relapse irrespective of technique.
      Coxph regression showed the risk of relapse after 4D brachytherapy was similar to
      the 2S technique (hazard ratio 0.67, 95% confidence interval 0.44-1.03, P =
      0.065). Forty-eight months post-implant there was a significantly greater
      proportion of 4D brachytherapy cases with a prostate-specific antigen below 0.4
      ng/ml relative to the 2S technique. Urinary and bowel symptom scores showed
      reduced toxicity after 4D implants and potency conservation was similar to the 2S
      technique. The reduction in time and resource use decreased the cost of 4D
      brachytherapy by 40% compared with the 2S technique. CONCLUSION: Two-stage and 4D
      brachytherapy are both highly effective for the control of localised prostate
      cancer. However, relative to the 2S technique, the 4D technique was associated
      with improved dosimetry, reduced treatment-related toxicity and reduced cost.
      Further follow-up will assess disease control superiority of 4D brachytherapy
      beyond 5 years post-implant.

PMID- 29054376
TI  - Patterns and correlates of treatment failure in relation to isodose distribution
      in non-small cell lung cancer: An analysis of 1522 patients in the modern era.
AB  - BACKGROUND AND PURPOSE: To examine the relationship between radiation dose and
      tumor control in limited stage non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: We searched a database of 1552 patients who received radiation therapy
      for non-metastatic NSCLC between 2000 and 2016. The primary endpoint was freedom
      from in-field failure. RESULTS: Increasing BED correlated with decreasing
      estimated gross tumor volume-planning target volume expansion, and on
      multivariable analysis increasing BED was associated with an increased chance of
      field-edge failures (hazard ratio [HR] 1.032, 95% confidence interval [CI] 1.004
      1.062, P = 0.027). Increasing BED also correlated with improved freedom from in
      field failure on multivariable analysis (HR 0.978, 95% CI 0.964-0.993, P =
      0.003), with the dose-response curve showing a sigmoidal relationship between
      increasing BED and freedom from in-field failure. CONCLUSION: In this large study
      of patients treated in the modern era with varying dose fractionation regimens,
      higher BED was associated with improved freedom from in-field failure, and that
      this relationship appeared to be consistent with the classically described
      sigmoid shape. We also found that increased BED was associated with higher field
      edge failures, implying that margin size may need to be further studied in
      patients receiving ablative regimens of radiation.

PMID- 29054377
TI  - Patterns of care and outcomes for use of concurrent chemoradiotherapy over
      radiotherapy alone for anaplastic gliomas.
AB  - BACKGROUND AND PURPOSE: The role of concurrent chemoradiotherapy (CRT) for
      anaplastic gliomas is undefined and patterns of care are under-reported. To
      address the knowledge gap, we examined use of CRT for grade III gliomas compared
      to radiotherapy (RT) alone. MATERIAL AND METHODS: In an observational study
      design cohort from the National Cancer Database, we identified 4437 adult
      patients receiving surgery followed by either CRT or RT for supratentorial
      anaplastic glioma in 2003-2011. Univariable and multivariable logistic regression
      analyses were used to assess factors associated with use of CRT. Overall survival
      (OS) was assessed by the Kaplan-Meier analysis with log-rank tests, Cox
      proportional hazards regression modeling, and propensity score matching. RESULTS:
      Receipt of CRT (vs. RT) was associated with recent year of diagnosis (OR for 2011
      (vs. 2003) 3.36, 95% CI 2.49-4.54) and having astrocytoma (vs. oligodendroglioma)
      (OR 1.37, 95% CI 1.15-1.63). Patients receiving CRT had a lower adjusted hazard
      of death (hazard ratio 0.72, 95% CI 0.65-0.79). Outcomes were worse for patients
      >=60 (HR 6.94, 95% CI 6.09-7.91) and astrocytomas (HR 2.08, 95% CI 1.85-2.34).
      CONCLUSION: Use of concurrent CRT is associated with more recent year of
      diagnosis and improved survival relative to RT alone.

PMID- 29054378
TI  - Multiple-CT optimization of intensity-modulated proton therapy - Is it possible
      to eliminate adaptive planning?
AB  - BACKGROUND AND PURPOSE: We hypothesized that a plan's robustness to anatomical
      changes can be improved by optimizing with multiple CT scans of a patient. The
      purpose of this study was to determine whether an intensity modulated proton
      therapy (IMPT) plan could be developed to meet dose criteria on both planning and
      adaptive CT plans. MATERIAL AND METHODS: Eight lung cancer patients who underwent
      adaptive IMPT were retrospectively selected. Each patient had two CTs: a primary
      planning CT (PCT) and an adaptive planning CT (ACT), and IMPT plans associated
      with the scans. PCT and ACT were then used in combination to optimize one plan
      (MCT plan). The doses to the target and organs at risk from the PCT plan, ACT
      plan, P-ACT plan (PCT plan calculated on ACT data), and MCT plans calculated on
      both CTs were compared. RESULTS: The MCT plan maintained the D95% on both CTs
      (mean, 65.99 Gy on PCT and 66.02 Gy on ACT). Target dose coverage on ACT was
      significantly better with the MCT plan than with the P-ACT plan (p = 0.01). MCT
      plans had slightly higher lung V20 (0.6%, p = 0.02) than did PCT plans. The
      various plans showed no statistically significant difference in heart and spinal
      cord dose. CONCLUSIONS: The results of this study indicate that an IMPT plan can
      meet the dose criteria on both PCT and ACT, and that MCT optimization can improve
      the plan's robustness to anatomical change.

PMID- 29054375
TI  - ATR/CHK1 inhibitors and cancer therapy.
AB  - The cell cycle checkpoint proteins ataxia-telangiectasia-mutated-and-Rad3-related
      kinase (ATR) and its major downstream effector checkpoint kinase 1 (CHK1) prevent
      the entry of cells with damaged or incompletely replicated DNA into mitosis when
      the cells are challenged by DNA damaging agents, such as radiation therapy (RT)
      or chemotherapeutic drugs, that are the major modalities to treat cancer. This
      regulation is particularly evident in cells with a defective G1 checkpoint, a
      common feature of cancer cells, due to p53 mutations. In addition, ATR and/or
      CHK1 suppress replication stress (RS) by inhibiting excess origin firing,
      particularly in cells with activated oncogenes. Those functions of ATR/CHK1 make
      them ideal therapeutic targets. ATR/CHK1 inhibitors have been developed and are
      currently used either as single agents or paired with radiotherapy or a variety
      of genotoxic chemotherapies in preclinical and clinical studies. Here, we review
      the status of the development of ATR and CHK1 inhibitors. We also discuss the
      potential mechanisms by which ATR and CHK1 inhibition induces cell killing in the
      presence or absence of exogenous DNA damaging agents, such as RT and
      chemotherapeutic agents. Lastly, we discuss synthetic lethality interactions
      between the inhibition of ATR/CHK1 and defects in other DNA damage response (DDR)
      pathways/genes.

PMID- 29054379
TI  - Treatment log files as a tool to identify treatment plan sensitivity to
      inaccuracies in scanned proton beam delivery.
AB  - Dose distributions delivered at Gantry 2 at the Paul Scherrer Institut (PSI) can
      be reconstructed on the patient anatomy based on machine log files. With the
      present work, the dependency of the log file calculation on the planning
      optimization technique and on other planning parameters, such as field direction
      and tumour size, has been investigated. Interestingly, and despite the typically
      higher modulation of Intensity Modulated Proton Therapy (IMPT) plans, the results
      for both Single Field Uniform Distribution and IMPT approaches have been found to
      be similar. In addition, complex fields with steep in-field dose gradients, such
      as Simultaneous Integrated Boost, and with couch movements in between the
      delivery, also resulted in good agreement between planned and reconstructed
      doses. Nevertheless, highly modulated plans can have regions of larger local dose
      deviations and attention should therefore be paid during the planning stage to
      the location of isolated, highly weighted pencil beams. We propose also, that
      further effort should be invested in order to predict field robustness to
      delivery fluctuations before the clinical delivery of the plan as part of the
      plan specific Quality Assurance.

PMID- 29054381
TI  - Comparing the coracoclavicular loop technique with a hook plate for the treatment
      of distal clavicle fractures.
AB  - BACKGROUND: Treatment of displaced distal clavicular fractures is still
      controversial. This study reports the utility of a new coracoclavicular (CC) loop
      technique for acute displaced distal clavicular fractures and compared its
      surgical outcomes with those of the hook plate method. METHODS: In this
      retrospective study, a total of 23 patients with acute displaced distal
      clavicular fractures were treated with a new CC loop technique at a single
      institution from 2010 to 2014. Another group comprising 49 patients treated with
      a hook plate was compared with the CC loop group regarding clinical and
      radiologic outcomes. RESULTS: Seventy-two patients with at least 1 year of follow
      up after both operations were included in this study. The Constant score was
      significantly greater in the CC loop group (95 vs 87, P = .009) at final follow
      up. Moreover, the complication rate was significantly lower in the CC loop group
      (0% vs 24.5%, P = .007). The University of California, Los Angeles shoulder score
      and radiologic nonunion rate revealed no significant differences between the 2
      groups. CONCLUSIONS: The new CC loop technique had better clinical outcomes and
      lower complication rates compared with the hook plate technique.

PMID- 29054380
TI  - Toxicity and efficacy of re-irradiation of high-grade glioma in a phase I dose-
      and volume escalation trial.
AB  - INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy
      of PET and MRI guided re-irradiation of recurrent high-grade glioma (HGG) and to
      assess the impact of radiotherapy dose, fractionation and irradiated volume.
      MATERIAL AND METHODS: Patients with localized, recurrent HGG (grades III-IV) and
      no other treatment options were eligible for a prospective phase I trial. Gross
      tumor volumes for radiotherapy were defined using T1-contrast enhanced MRI and
      18F-fluoro-ethyl tyrosine PET. Radiotherapy was delivered using volumetric
      modulated arc therapy with a 2-mm margin. The dose prescription of four
      consecutive groups was (1) 35 Gy/10fr., (2) 42 Gy/10fr., (3) 29.5 Gy/5fr. and (4)
      35 Gy/10fr. to larger tumor volumes (100-300 cm3), respectively. RESULTS: Thirty
      one patients were treated of which 81% had glioblastoma. The median progression
      free survival was 2.8 months (95%CI: 2.1-3.5) and the median overall survival was
      7.0 months (95%CI: 3.5-10.5). Early side effects were mild and included headache
      and fatigue. Seven patients were progression-free beyond 10 weeks and were
      evaluable for late toxicity. Among these patients, three (43%) suffered late
      adverse events which included radionecrosis and irreversible white matter
      changes. CONCLUSION: Re-irradiation showed limited efficacy and 43% of patients
      achieving disease control suffered late toxicity that was manageable but not
      negligible.

PMID- 29054382
TI  - Outcome of conservative treatment for Little League shoulder in young baseball
      players: factors related to incomplete return to baseball and recurrence of pain.
AB  - BACKGROUND: The purpose of this study was to investigate the factors associated
      with poor results and pain recurrence in young baseball players with Little
      League shoulder (LLS). METHODS: Eighty-seven young baseball players with LLS
      (mean age, 12.1 years) underwent conservative treatment. Of the players, 68 (78%)
      underwent conservative treatment involving the prohibition of throwing for an
      average of 1.2 months whereas the remaining 19 (22%) continued throwing with
      limitations. We analyzed the factors associated with poor results at 2 months and
      pain recurrence. RESULTS: At 2 months, 18% of participants reported the presence
      of pain, and the results regarding the return to baseball were as follows:
      complete return in 43%, incomplete return in 33%, and no return in 24%. A total
      of 83 subjects (95%) had completely returned at an average of 2.8 months. Pain
      recurrence was present in 20 subjects (25%) at an average of 6.2 months.
      Statistical analysis showed that the following factors were significantly
      associated with poor results at 2 months: longer period from initial presentation
      to throwing prohibition and worse shoulder flexibility (P = .04 and P = .01,
      respectively). It also revealed that the following factors were significantly
      associated with pain recurrence: higher frequency of pain at 2 months and longer
      duration until complete return (P = .0003 and P = .04, respectively).
      CONCLUSIONS: It is important for subjects with LLS to be prohibited from throwing
      immediately after initial presentation. Good shoulder flexibility was associated
      with a return to baseball without pain. A complete return in subjects who had
      pain at 2 months was significantly delayed, and these subjects exhibited more
      rapidly recurring pain after their return.

PMID- 29054383
TI  - Arthroscopic surgical treatment of medial epicondylitis.
AB  - BACKGROUND: The study purpose was to evaluate the outcomes of patients who
      received arthroscopic surgical treatment for medial epicondylitis refractory to
      conservative treatment. METHODS: This was a retrospective study of 7 patients who
      underwent arthroscopic surgical debridement of the common flexor tendon for
      treatment of medial epicondylitis refractory to conservative treatment. The
      patients were assessed using the Disabilities of the Arm, Shoulder and Hand
      score; visual analog scale for pain; and Short Form 36 Health Survey. The mean
      age at the time of surgery was 50 years (range, 36-67 years). The mean duration
      of symptoms before surgery was approximately 2 years (range, 8 months to 4
      years). The mean follow-up duration was 17 months (range, 6-48 months). RESULTS:
      The average postoperative scores were 17 points on the Disabilities of the Arm,
      Shoulder and Hand outcome measure; 2 points on the visual analog scale at rest
      for 6 subjects (86%) with slight pain and 1 (14%) with moderate pain; and 78 on
      the Short Form 36 Health Survey. No significant complications were observed when
      the procedure was performed via arthroscopy. CONCLUSION: Arthroscopic surgical
      treatment for medial epicondylitis of the elbow exhibits good outcomes and is
      safe and effective.

PMID- 29054384
TI  - Arthroscopic subscapularis repair using single-row mattress suture technique:
      clinical results and structural integrity.
AB  - BACKGROUND: Rupture of the subscapularis (SSC) tendon, isolated or combined, is
      rare, and the treatment modalities are controversial. The purpose of this study
      was to evaluate, by magnetic resonance imaging (MRI), the clinical outcomes and
      structural integrity of the SSC tendon after all-arthroscopic repair with single
      row mattress suture for isolated or combined SSC tendon tears. METHODS: This
      study included 68 patients who underwent all-arthroscopic repair using single-row
      mattress suture for isolated or combined SSC tendon tears between April 2011 and
      January 2013. The patients were evaluated by the visual analog scale for pain,
      American Shoulder and Elbow Surgeons score, Constant shoulder score, and SSC
      muscle strength measurement. MRI was used for assessment of the postoperative
      integrity of the SSC tendon. RESULTS: With a mean follow-up of 29.5 +/- 4.0
      months, the preoperative Constant shoulder and American Shoulder and Elbow
      Surgeons scores were 50.3 +/- 21.0 and 46.6 +/- 18.3, respectively, which
      improved at the last follow-up to 75.7 +/- 16.6 and 81.3 +/- 18.1, respectively,
      with statistical significance (P < .001). Belly-press and bear-hug test results
      showed some improvement in the last follow-up (>2 years) compared with the
      presurgical state (P = .125 and .650). A statistically significant SSC muscle
      strength deficit persisted in the postoperative state (P = .015). MRI evaluation
      showed a retear rate of 8.8%. CONCLUSIONS: Arthroscopic repair of isolated or
      combined SSC tears with the single-row mattress suture technique results in
      significant clinical improvements and enduring tendon integrity, although SSC
      strength remains reduced from that on the normal side.

PMID- 29054385
TI  - Functionalized calcium carbonate microparticles for the delivery of proteins.
AB  - The recently introduced functionalized calcium carbonate (FCC), a porous
      microparticle with a nano-structured, lamellar surface, shows promising
      properties in the field of oral drug delivery. In this work, FCC was loaded with
      biomolecules e.g. lysozyme (Lys) and bovine serum albumin (BSA) in order to
      investigate its suitability to deliver protein based drugs. Loading efficiency
      for our model proteins was >90% and enzyme activity was preserved as demonstrated
      by Michaelis-Menten enzyme kinetic experiments. Circular dichroism analysis
      confirmed, that neither the structure of both model substances, nor the activity
      of Lys was affected by the loading process or the interaction with the surface of
      FCC. Electron microscopy (SEM) and mercury porosimetry were indicative of protein
      deposition on the particle surface as well as within the particle pores. Release
      properties were investigated in a customized flow cell, which simulates the
      conditions in the oral cavity. Depending on the isoelectric point of the
      investigated proteins, complete release was obtained within 1.5h. This work
      shows, that FCC is a suitable pharmaceutical excipient for delivery of proteins.

PMID- 29054386
TI  - Interlaced Size Exclusion Chromatography for faster protein analysis.
AB  - In this research note, interlaced Size Exclusion Chromatography (SEC) is used to
      shorten the duration of protein analysis. The applied method has a threefold
      higher sample throughput than comparable ones using conventional SEC. Further
      important advantages are the identical area's precision and the preservation of
      protein stability. Two different applications are presented where a short time
      interval of analysis is very important. One application is the determination of
      aggregates of monoclonal antibodies (mAbs). A high number of antibody samples
      have to be analyzed during the development process. The antibody sample was
      measured in a series of 60 injections within only 5.5 h instead of 16 h. The
      second application is the two-dimensional (2 D) separation of protein mixtures.
      The number of samples typically increases from the first to the second dimension.
      Thus, interlaced SEC is a reasonable option for the second dimension. This work
      confirms the functionality of interlaced SEC and widens the applicable range.
      Interlaced SEC can become a convenient option for method acceleration in the
      future.

PMID- 29054387
TI  - The post-natal development of intraocular pressure in normal domestic cats (Felis
      catus) and in feline congenital glaucoma.
AB  - Intraocular pressure (IOP) is the most consistent risk factor for progressive
      vision loss in glaucoma. Cats with recessively inherited feline congenital
      glaucoma (FCG) exhibit elevated IOP with gradual, painless progression of
      glaucoma similar to humans and are studied as a model of glaucoma in humans and
      animals. Here, post-natal development of IOP was characterized in normal domestic
      cats and in cats with FCG caused by a homozygous LTBP2 mutation. Rebound
      tonometry (TonoVet(r), ICare Oy, Finland) was used to measure IOP non-invasively,
      2-3 times weekly in 63 FCG and 33 normal kittens, of both sexes, from eyelid
      opening until 3-6 months of age. IOPs in the left and right eyes of both FCG and
      normal kittens were compared by paired t-test and linear regression. One-way
      ANOVA and Tukey-Kramer post-tests were used to compare IOP of cats grouped by age
      and disease status. A p-value <0.05 was considered significant. In the second
      week of life, mean IOP was 7.16 mmHg (SD = 1.3) in normal kittens and 8.72 mmHg
      (SD = 1.4) in kittens with FCG. Mean IOP at age 10 weeks was significantly higher
      in FCG (19.8 mmHg; 95% CI = 17.7, 21.9  mmHg) than in normal kittens (13.2 mmHg;
      95% CI = 11.9, 14.5  mmHg). At 3 months of age, IOP in normal cats reached adult
      values while IOP in FCG cats continued to increase through at least six months of
      age. These results provide ranges for normal IOP values in young kittens and
      confirm that IOP is significantly higher than normal by 10wks of age in this
      spontaneous feline glaucoma model.

PMID- 29054388
TI  - Comparative effectiveness of a pilot patient-centered ultrasound report in the
      management of hydronephrosis.
AB  - PURPOSE: Hydronephrosis is a common pediatric abnormality and can be associated
      with substantial parental anxiety, especially in the prenatal period. Radiology
      reports contain complex content that can be difficult for lay audiences to
      comprehend, potentially contributing to parental distress. MATERIALS AND METHODS:
      We developed and piloted a patient-centered radiology report (PCRR) for renal
      ultrasounds (US) in children with hydronephrosis (Figure). We obtained consensus
      from a multidisciplinary panel of experts regarding critical US report
      components. A parent focus group provided input regarding syntax and formatting
      of a PCRR, incorporating elements deemed valuable by the expert panel. We
      prospectively recruited parents of children who underwent US for hydronephrosis
      and randomized parents to receive either the PCRR + standard report (SR) or SR
      alone. Web-based surveys assessed self-efficacy and knowledge of US elements.
      RESULTS: Our pilot study included 20 SR patients and 24 PCRR patients, with no
      difference in demographic or disease characteristics between groups. Self
      efficacy scores were uniformly high in both groups (p = 0.79). PCRR parents
      trended towards increased accuracy in identifying presence of severity (88% vs.
      70%; p = 0.15) and bilaterality (67% vs. 45%; p = 0.15), with minimal difference
      in identifying parenchymal pathology (75% vs. 70%; p = 0.71) and bladder
      abnormalities (88% vs. 85%; p = 0.81). Parents were more confident in their
      ability to understand the PCRR (92% vs. 60%; p = 0.01). CONCLUSIONS: A PCRR was
      associated with significantly higher confidence in US report interpretation, but
      was underpowered to demonstrate increased accuracy in identifying US findings.
      These findings justify future studies of PCRRs for hydronephrosis care.

PMID- 29054389
TI  - Optimizing Surgical Quality Datasets to Care for Older Adults: Lessons from the
      American College of Surgeons NSQIP Geriatric Surgery Pilot.
AB  - BACKGROUND: Surgical quality datasets can be better tailored toward older adults.
      The American College of Surgeons (ACS) NSQIP Geriatric Surgery Pilot collected
      risk factors and outcomes in 4 geriatric-specific domains: cognition, decision
      making, function, and mobility. This study evaluated the contributions of
      geriatric-specific factors to risk adjustment in modeling 30-day outcomes and
      geriatric-specific outcomes (postoperative delirium, new mobility aid use,
      functional decline, and pressure ulcers). STUDY DESIGN: Using ACS NSQIP Geriatric
      Surgery Pilot data (January 2014 to December 2016), 7 geriatric-specific risk
      factors were evaluated for selection in 14 logistic models
      (morbidities/mortality) in general-vascular and orthopaedic surgery subgroups.
      Hierarchical models evaluated 4 geriatric-specific outcomes, adjusting for
      hospitals-level effects and including Bayesian-type shrinkage, to estimate
      hospital performance. RESULTS: There were 36,399 older adults who underwent
      operations at 31 hospitals in the ACS NSQIP Geriatric Surgery Pilot. Geriatric
      specific risk factors were selected in 10 of 14 models in both general-vascular
      and orthopaedic surgery subgroups. After risk adjustment, surrogate consent (odds
      ratio [OR] 1.5; 95% CI 1.3 to 1.8) and use of a mobility aid (OR 1.3; 95% CI 1.1
      to 1.4) increased the risk for serious morbidity or mortality in the general
      vascular cohort. Geriatric-specific factors were selected in all 4 geriatric
      specific outcomes models. Rates of geriatric-specific outcomes were:
      postoperative delirium in 12.1% (n = 3,650), functional decline in 42.9% (n =
      13,000), new mobility aid in 29.7% (n = 9,257), and new or worsened pressure
      ulcers in 1.7% (n = 527). CONCLUSIONS: Geriatric-specific risk factors are
      important for patient-centered care and contribute to risk adjustment in modeling
      traditional and geriatric-specific outcomes. To provide optimal patient care for
      older adults, surgical datasets should collect measures that address cognition,
      decision-making, mobility, and function.

PMID- 29054391
TI  - Nuclear movement and positioning in plant cells.
AB  - Plant cells connected to adjacent cells with rigid cell wall cannot change their
      position, so that appropriate nuclear positioning according to nuclear movement
      is indispensable for cellular development involving unequal cell division.
      Sessile plants are severely affected by fluctuating environmental conditions, so
      that movement of organelles including nucleus is fundamental to accomplish
      physiological functions. The mechanisms of nuclear movement and their purposes
      studied recently with Arabidopsis thaliana, the model plants for genetics and
      molecular biology, and the nuclear behavior in fern gametophytes, an apical
      growing protonemal cell and a two-dimensional prothallus of Adiantum capillus
      veneris, the model plants for cell biology and photobiology are described in this
      review.

PMID- 29054390
TI  - Oral pioglitazone ameliorates fructose-induced peripheral insulin resistance and
      hippocampal gliosis but not restores inhibited hippocampal adult neurogenesis.
AB  - Diet-associated insulin resistance (IR) is intimately correlated with the
      progression of metabolic syndrome and hippocampal dysfunction. Pioglitazone
      (PIO), a selective peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonist, has been applied to enhance insulin sensitivity. With limited
      permeability to blood-brain-barrier, it is unclear that whether oral PIO
      available to cure both the peripheral IR and the impairment in the hippocampus.
      We evaluated the levels of peripheral and hippocampal IR via the homeostatic
      model assessment of insulin resistance and hippocampal IRS-1/Akt phosphorylation,
      respectively, of Wistar Kyoto rats fed with a regular chew or high fructose diet
      (HFD) for 12weeks. Gavage with PIO (30mg/kg/day, 2weeks) significantly reduced
      the peripheral IR and reversed the level of hippocampal PPARgamma. Moreover, HFD
      activated microglia and astrocyte were effectively relieved by PIO. The
      suppressed brain-derived neurotrophic factor, CaMKIIalpha, and postsynaptic
      density protein 95 in the hippocampus were effectively reversed by PIO. However,
      the hippocampal IR and inhibition of adult neurogenesis in dentate gyrus were not
      restored by PIO. Together, PIO oral application may reverse the HFD-induced
      peripheral IR and maintain the existed neuronal circuit by ameliorating glial
      activation and enhancing synaptic density through BDNF but failed to restore
      adult neurogenesis in the hippocampus.

PMID- 29054392
TI  - Impairment of manual but not saccadic response inhibition following acute alcohol
      intoxication.
AB  - BACKGROUND: Alcohol impairs response inhibition; however, it remains contested
      whether such impairments affect a general inhibition system, or whether affected
      inhibition systems are embedded in, and specific to, each response modality.
      Further, alcohol-induced impairments have not been disambiguated between
      proactive and reactive inhibition mechanisms, and nor have the contributions of
      action-updating impairments to behavioural 'inhibition' deficits been
      investigated. METHODS: Forty Participants (25 female) completed both a manual and
      a saccadic stop-signal reaction time (SSRT) task before and after a 0.8g/kg dose
      of alcohol and, on a separate day, before and after a placebo. Blocks in which
      participants were required to ignore the signal to stop or make an additional
      'dual' response were included to obtain measures of proactive inhibition as well
      as updating of attention and action. RESULTS: Alcohol increased manual but not
      saccadic SSRT. Proactive inhibition was weakly reduced by alcohol, but increases
      in the reaction times used to baseline this contrast prevent clear conclusions
      regarding response caution. Finally, alcohol also increased secondary dual
      response times of the dual task uniformly as a function of the delay between
      tasks, indicating an effect of alcohol on action-updating or execution.
      CONCLUSIONS: The modality-specific effects of alcohol favour the theory that
      response inhibition systems are embedded within response modalities, rather than
      there existing a general inhibition system. Concerning alcohol, saccadic control
      appears relatively more immune to disruption than manual control, even though
      alcohol affects saccadic latency and velocity. Within the manual domain, alcohol
      affects multiple types of action updating, not just inhibition.

PMID- 29054393
TI  - Isolation of Candida spp. from denture-related stomatitis in Para, Brazil.
AB  - The aim of this study was to isolate and identify Candida species from the oral
      cavity of denture wearers with denture-related stomatitis who were attended at
      the University Federal of Para (Belem City, Para State, Brazil). A total of 36
      denture wearers with denture-related stomatitis were included, and type I (50%),
      type II (33%) and type III (17%) stomatitis were observed. Candida spp. were
      isolated from 89% of the cases and included five different Candida species. C.
      albicans was the most frequently recovered species (78% of the cases), followed
      by C. famata and C. tropicalis. We observed a significant association between
      Candida species isolation and unsatisfactory denture condition (p=0.0017). Our
      results demonstrated the highly frequency of Candida species isolation in denture
      wearers with denture-related stomatitis and showed the relationship between these
      species and poor denture maintenance.

PMID- 29054394
TI  - Immediate postoperative Fibrosis-4 predicts postoperative liver failure for
      patients with hepatocellular carcinoma undergoing curative surgery.
AB  - BACKGROUND: Postoperative liver failure remains the main complication and
      predominant cause of hepatectomy-related mortality for patients undergoing liver
      resection. AIM: Our aim is to investigate whether immediate postoperative
      Fibrosis-4 could predict postoperative liver failure. METHODS: We retrospectively
      enrolled 1353 consecutive hepatocellular carcinoma patients undergoing radical
      resection. The characteristics and clinical outcomes were compared between
      patients with high and low immediate postoperative Fibrosis-4. Risk factors for
      hepatic failure were evaluated by univariate and multivariate analysis. RESULTS:
      Using a receiver operating characteristic curve, immediate postoperative Fibrosis
      4 showed good prediction ability for postoperative liver failure (AUROC=0.647,
      P<0.001). With the optimal cut-off value of 5.9, the high postoperative Fibrosis
      4 group (Fibrosis-4<5.9) had higher postoperative complication (39.1% vs 28.6%,
      P<0.001), mortality (2.8% vs 0.6%, P<0.001) and liver failure (13.9% vs 6.2%,
      P<0.001). In addition, patients with high Fibrosis-4 had worse and delayed
      recovery of liver function. By univariate and multivariate analysis, Fibrosis-4,
      as well as liver removed volume, total bilirubin and albumin was identified as
      independent risk factor for postoperative liver failure. CONCLUSIONS: Immediate
      postoperative Fibrosis-4 showed good prediction ability for postoperative liver
      failure, and required measure should be taken to prevent liver failure when high
      postoperative Fibrosis-4 appeared.

PMID- 29054395
TI  - Obstructive sleep apnea is predictive of worse hospital outcomes in
      hospitalizations with acute pancreatitis in obese patients.

PMID- 29054396
TI  - Clinical outcome after biliary drainage for metastatic colorectal cancer:
      Survival analysis and prognostic factors.
AB  - INTRODUCTION: Biliary obstruction secondary to colorectal cancer liver metastases
      is associated with a poor prognosis especially when chemotherapy cannot be re
      started. The aim of this study was to determine the survival after biliary
      drainage and the associated prognostic factors. METHODS: Patients from two French
      centers were included retrospectively after first biliary endoscopic retrograde
      cholangiopancreatography or percutaneous transhepatic cholangiography drainage
      for biliary obstruction secondary to liver metastases of colorectal cancer,
      occurring during chemotherapy. RESULTS: The final analysis included 69 patients.
      Overall median survival was 115 days. In univariate analysis, a previous liver
      surgery, technical and functional success of drainage and restarted chemotherapy
      were significantly associated with an improved survival. Chemotherapy was
      restarted after a median of 27 days. When drainage was efficient, survival
      improved from 33 to 262days (p<0.001). In multivariate analysis, significant
      protective factors for survival included previous a hepatectomy (HR 0.41) and
      functional success of the drainage (HR 0.29). Predictive factors for death
      included increased lines of chemotherapy (HR 1.68) and fever before drainage (HR
      2.97). CONCLUSIONS: This is the first study concerning the benefits of biliary
      drainage for malignant biliary obstruction during the course of chemotherapy for
      colorectal cancer. A successful biliary drainage leads to improved survival and
      allows achievement of chemotherapy for 70% of patients.

PMID- 29054397
TI  - Tolerance in clinical liver transplantation.
AB  - While advances in immunosuppressive therapy have lowered the rate of acute
      rejection following liver transplantation, the consequence has been an increase
      in morbidity and mortality related to the lifelong need for maintenance
      immunosuppression. These complications include an increased risk of malignancy,
      infection, metabolic disorders, and chronic kidney disease, as well as high
      health care costs associated with these therapies and the required drug
      monitoring. Given these issues, most clinicians attempt trial and error dose
      minimization with variable success rates, and there has been significant interest
      in full drug withdrawal in select patients through research protocols. These
      strategies would be more successful if immunomodulatory therapies early after
      transplantation could be developed and if immune activation biomarkers guiding
      drug tapering were available to personalize these approaches. This review will
      review the mechanisms of liver transplant tolerance and potential strategies to
      achieve immunosuppression withdrawal.

PMID- 29054398
TI  - Association of TNF-Alpha gene polymorphisms and susceptibility to hepatitis B
      virus infection in Egyptians.
AB  - Tumor necrosis factor alpha (TNF-alpha) is one of the important cytokine in
      generating an immune response against hepatitis B virus (HBV). Genetic
      polymorphisms might influence gene transcription, leading to disturbance in
      cytokine production. We hypothesized that single nucleotide polymorphism (SNPs)
      in TNF-alpha gene could affect the pathogenesis of HBV. To test this hypothesis,
      we investigated the role of TNF-alpha polymorphism [-863C/A (rs1800630), -308G/A
      (rs1800629), -376G/A (rs1800750), -857C/T (rs1799724) and +489G/A (rs1800610)] in
      the susceptibility to chronic hepatitis B (CHB) infection. Polymorphisms of the
      TNF-alpha (-863C/A (rs1800630), -308G/A) were analyzed by Polymerase chain
      reaction sequence specific primer (PCR-SSP) while TNF-alpha (-376G/A, -857C/T and
      +489G/A) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 104
      patients with CHB and 104 healthy controls. The plasma level of TNF-alpha was
      measured using Enzyme-linked immunosorbent assay (ELISA). The study showed a
      significant increase in the frequency of -863CC, -376GA, -857CC, -857TT and
      +489GA genotypes and -863C, -376A, -857C, and +489A alleles in CHB patients
      compared to controls. In addition, CAGCG haplotype had a highest frequency in CHB
      patients. A strong Linkage Disequilibrium (LD) between TNF-alpha -863C/A
      (rs1800630) and -376G/A (D' = 0.7888, r2 = 0.0200); -308G/A and -857C/T (D' =
      0.9213, r2 = 0.1770); -308G/A and +489G/A (D' = 0.9088, r2 = 0.1576) was
      demonstrated. CHB patients had significantly lower levels of TNF-alpha compared
      to controls. In conclusion, our preliminary results suggest that -863C/A
      (rs1800630), -308G/A, -376G/A, and +489G/A of the TNF-alpha gene may play a role
      in HBV susceptibility in Egyptians. The significant reduction in TNF-alpha in CHB
      patient was independent of any particular genotype/haplotype in TNF-alpha.

PMID- 29054399
TI  - Determination of Molecular Subtypes of Diffuse Large B-Cell Lymphoma Using a
      Reverse Transcriptase Multiplex Ligation-Dependent Probe Amplification
      Classifier: A CALYM Study.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It
      includes three major subtypes termed germinal center B-cell-like, activated B
      cell-like, and primary mediastinal B-cell lymphoma. With the emergence of novel
      targeted therapies, accurate methods capable of interrogating this cell-of-origin
      classification should soon become essential in the clinics. To address this
      issue, we developed a novel gene expression profiling DLBCL classifier based on
      reverse transcriptase multiplex ligation-dependent probe amplification. This
      assay simultaneously evaluates the expression of 21 markers, to differentiate
      primary mediastinal B-cell lymphoma, activated B-cell-like, germinal center B
      cell-like, and also Epstein-Barr virus-positive DLBCLs. It was trained using 70
      paraffin-embedded biopsies and validated using >160 independent samples. Compared
      with a reference classification established from Affymetrix U133 + 2 data,
      reverse transcriptase multiplex ligation-dependent probe amplification classified
      85.0% samples into the expected subtype, comparing favorably with current
      diagnostic methods. This assay also proved to be highly efficient in detecting
      the MYD88 L265P mutation, even in archival paraffin-embedded tissues. This
      reliable, rapid, and cost-effective method uses common instruments and reagents
      and could thus easily be implemented into routine diagnosis workflows, to improve
      the management of these aggressive tumors.

PMID- 29054400
TI  - Barriers to delirium assessment in the intensive care unit: A literature review.
AB  - BACKGROUND: Delirium is a common syndrome that has both short and long-term
      negative outcomes for critically ill patients. Many studies over several years
      have found a knowledge gap and lack of evidence-based practice from critical care
      personnel, but there has been little exploration of the reasons for this. AIM: To
      identify the perceived barriers to delirium assessment and management among
      critical care nurses. METHOD: A literature review of published studies to examine
      barriers to effective delirium assessment using a comprehensive search strategy.
      Five relevant studies identified for review. RESULTS: Few studies have
      investigated barriers to delirium assessment and management, but several themes
      reoccur throughout the literature. The perceived time consuming nature of the
      assessment tools is cited by many, as is the lack of medical prioritisation of
      results. Lack of education on delirium appears to be a significant factor and
      reinforces some of the stated misconceptions. CONCLUSION: Many barriers exist to
      prevent effective assessment and management of delirium, but several of these are
      due to a lack of understanding or unfamiliarity with the condition and the
      assessment tools as well as lack of medical prioritisation of the results.
      Further research is needed on this topic.

PMID- 29054401
TI  - The evaluation of nurse driven treatments starts with the nurses.

PMID- 29054402
TI  - From the President, American Society of Hypertension.

PMID- 29054403
TI  - Top surface blade residues and the central channel water molecules are conserved
      in every repeat of the integrin-like beta-propeller structures.
AB  - An integrin-like beta-propeller domain contains seven repeats of a four-stranded
      antiparallel beta-sheet motif (blades). Previously we described a 3D structural
      motif within each blade of the integrin-type beta-propeller. Here, we show unique
      structural links that join different blades of the beta-propeller structure,
      which together with the structural motif for a single blade are repeated in a
      beta-propeller to provide the functional top face of the barrel, found to be
      involved in protein-protein interactions and substrate recognition. We compare
      functional top face diagrams of the integrin-type beta-propeller domain and two
      non-integrin type beta-propeller domains of virginiamycin B lyase and WD Repeat
      Containing Protein 5.

PMID- 29054404
TI  - Fat suppression at three-dimensional T1-weighted MR imaging of the hands: Dixon
      method versus CHESS technique.
AB  - PURPOSE: To compare the effectiveness of fat suppression and the image quality of
      the Dixon method with those of the chemical shift-selective (CHESS) technique in
      hands of normal subjects at non-enhanced three-dimensional (3D) T1-weighted MR
      imaging. MATERIALS AND METHODS: Both hands of 14 healthy volunteers were imaged
      with 3D fast spoiled gradient echo (FSPGR) T1-weighted Dixon, 3D FSPGR T1
      weighted CHESS and 3D T1-weighted fast spin echo (FSE) CHESS sequences in a 1.5T
      MR scanner. Three radiologists scored the effectiveness of fat suppression in
      bone marrow (EFSBM) and soft tissues (EFSST) in 20 joints per subject. One
      radiologist measured the signal-to-noise ratio (SNR) in 10 bones per subject.
      Statistical analysis used two-way ANOVA with random effects (P<0.0083), paired t
      test (P<0.05) and observed agreement to assess differences in effectiveness of
      fat suppression, differences in SNR and interobserver agreement. RESULTS: EFSBM
      was statistically significantly higher for the 3D FSPGR T1-weighted Dixon than
      for the 3D FSPGR T1-weighted CHESS sequence and the 3D FSE T1-weighted CHESS
      sequence (P<0.0001). EFSST was statistically significantly higher for the 3D
      FSPGR T1-weighted Dixon than for the 3D FSPGR T1-weighted CHESS sequence
      (P<0.0011) and for the 3D FSE T1-weighted CHESS sequence in the axial plane
      (P=0.0028). Mean SNR was statistically significantly higher for 3D FSPGR T1
      weighted Dixon sequence than for 3D FSPGR T1-weighted CHESS and 3D FSE T1
      weighted CHESS sequences (P<0.0001). CONCLUSION: The Dixon method yields more
      effective fat suppression and higher SNR than the CHESS technique at 3D T1
      weighted MR imaging of the hands.

PMID- 29054405
TI  - Standardized extract of Bacopa monnieri (CDRI-08): Effect on germ cell dynamics
      and possible mechanisms of its beneficial action on spermatogenesis and sperm
      quality in male mice.
AB  - Bacopa monnieri (BM) is used in traditional medicine as nerve tonic. We have
      recently shown that CDRI-08, a standardized extract of BM, improves testicular
      functions and epididymal sperm quality in Parkes (P) mice. The aim of the present
      study was to investigate the effect of CDRI-08 on germ cell dynamics and
      mechanisms of its action on spermatogenesis and sperm quality in P mice, and to
      determine the chemical profile of the extract. CDRI-08 (40 and 80 mg/kg body
      weight) was orally administered to male mice for 28 days. Germ cell dynamics,
      oxidative stress parameters in testis and sperm, and expressions of nuclear
      factor-erythroid-2-related factor-2 (Nrf2), phosphorylated protein kinase B (p
      Akt) and upstream kinases in mitogen-activated protein kinase (MAPK) pathway
      namely MAP2K1, MAP2K2 and MKK4 in the testis were evaluated. The treatment
      potentiated germ cell dynamics and improved sperm quality by enhancing
      antioxidant enzymes activities. The beneficial effects of CDRI-08 in the testis
      involve p-Akt-mediated activation of Nrf2, thereby enhancing antioxidant enzymes
      activities; upregulation of MAP2K1 and MAP2K2 and suppression of MKK4 are also
      implicated in this action. A total of 26 phytocomponents were identified in CDRI
      08 by GC-MS. The results suggest that CDRI-08 also may prove useful in improving
      reproductive health in males.

PMID- 29054406
TI  - A novel puromycin decorporation method to quantify skeletal muscle protein
      breakdown: A proof-of-concept study.
AB  - The precise roles that the major proteolytic pathways play in the regulation of
      skeletal muscle mass remain incompletely understood, in part due to technical
      limitations associated with current techniques used to quantify muscle protein
      breakdown (MPB). We aimed to develop a method to assess MPB in cells, based on
      loss of puromycin labelling of translated polypeptide chains. Following an
      initial 24 h incubation period with puromycin (1 MUM), loss of puromycin
      labelling from murine C2C12 myotubes was assessed over 48 h, both in the presence
      or absence of protein synthesis inhibitor cycloheximide (CHX). To validate the
      method, loss of puromycin labelling was determined from cells treated with
      selected compounds known to influence MPB (e.g. serum starvation, Dexamethasone
      (Dex), tumour necrosis factor alpha (TNF-alpha) and MG-132)). Reported
      established (static) markers of MPB were measured following each treatment. Loss
      of puromycin labelling from cells pre-incubated with puromycin was evident over a
      48 h period, both with and without CHX. Treatment with Dex (-14 +/- 2% vs. Ctl; P
      < 0.01), TNF-alpha (-20 +/- 4% vs. Ctl; P < 0.001) and serum starvation (-14 +/-
      4% vs. Ctl; P < 0.01) caused a greater loss of puromycin labelling than untreated
      controls, while the proteasome inhibitor MG-132 caused a relatively lower loss of
      puromycin labelling (+15 +/- 8% vs. Ctl; P < 0.05). Thus, we have developed a
      novel decorporation method for measuring global changes in MPB, validated in
      vitro using an established muscle cell line. It is anticipated this non isotopic
      tracer alternative to measuring MPB will facilitate insight into the mechanisms
      that regulate muscle mass/MPB both in vitro, and perhaps, in vivo.

PMID- 29054407
TI  - Ubiquitination of non-lysine residues in the retroviral integrase.
AB  - Retroviral integrase catalyzes the integration of retroviral genome into host
      chromosomal DNA, which is a prerequisite of effective viral replication and
      infection. The human immunodeficiency virus type 1 (HIV-1) integrase has
      previously been reported to be regulated by the ubiquitination, but the molecular
      characterization of integrase ubiquitination is still unclear. In this study, we
      analyzed the ubiquitination of avian leukosis virus (ALV) integrase in detail.
      The ubiquitination assay showed that, like HIV-1, ALV integrase could also be
      modified by ubiquitination when expressed in 293 T and DF-1 cells. Domain mapping
      analysis revealed that the ubiquitination of ALV integrase might mainly occurred
      in the catalytic core and the N-terminal zinc-binding domains. Both lysine and
      non-lysine residues within integrase of ALV and HIV-1 were responsible for the
      ubiquitin conjugation, and the N-terminal HHCC zinc-binding motif might play an
      important role in mediating integrase ubiquitination. Interestingly, mass
      spectrometry analysis identified the Thr10 and Cys37 residues in the HHCC zinc
      binding motif as the ubiquitination sites, indicating that ubiquitin may be
      conjugated to ALV integrase through direct interaction with the non-lysine
      residues. These findings revealed the detailed features of retroviral integrase
      ubiquitination and found a novel mechanism of ubiquitination mediated by the non
      lysine residues within the N-terminal zinc-binding domain of integrase.

PMID- 29054408
TI  - HDAC6 deficiency induces apoptosis in mesenchymal stem cells through p53 K120
      acetylation.
AB  - The acetylation of p53 is critical in modulating its pro-apoptotic roles.
      However, its regulatory mechanism and physiological significance are unclear.
      Here, we show HDAC6 negatively regulates pro-apoptotic acetylation of p53 at
      lysine residue 120 (K120) in mesenchymal stem cells (MSCs). The loss of HDAC6
      expression in MSCs increases K120 acetylation of p53, which is successfully
      reversed by the wild-type but not by catalytically dead HDAC6. Deletion of HDAC6
      induces caspase-dependent apoptosis by promoting transactivation of Bax and
      suppression of Bcl-2. Moreover, HDAC6 deficiency leads to mitochondrial
      dysfunction characterized by aberrant reactive oxygen species production and
      defective oxidative phosphorylation, which is reversed by ectopic expression of
      wild-type or acetylation mimetic p53. This study demonstrates that HDAC6 is a
      critical regulator of a pro-apoptotic p53 K120 acetylation and mitochondrial
      function in MSCs, suggesting that the modulation of HDAC6 activity could be a
      novel approach to improve MSC- based therapies.

PMID- 29054409
TI  - Dual expression of constitutively active Galphas-protein-coupled receptors
      differentially establishes the resting activity of the cAMP-gated HCN2 channel in
      a single compartment.
AB  - The hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channel is a
      major subtype of the HCN channel family expressed in the nervous system that sets
      the membrane potential, regulates cell excitability and senses changes in the
      extracellular environment. Neurons express various Galphas-protein-coupled
      receptors (GPCRs), many of which show ligand-independent constitutive activity.
      These membrane-bound proteins are expressed in various subcellular compartments
      of neurons. Therefore, some proportion of HCN2 channels opens in response to the
      basal cAMP pool size produced by constitutively active GPCRs. Here, we employed
      an exogenous HEK293 expression system and voltage-clamp patch-clamp recordings to
      investigate basal HCN2 channel activity in the presence of two GPCRs with diverse
      basal activities in a single compartment. We utilized the beta2-adrenoceptor
      (beta2AR) together with odorant receptors (ORs), as both GPCR families are known
      to show strong basal activity. Consequently, beta2AR alone strongly enhanced the
      activity of HCN2 channels, and co-expression of ORs further diversified the HCN2
      channel activity, which was totally abolished by an adenylate cyclase inhibitor.
      Thus, we conclude that the dual expression of constitutively active GPCRs
      establishes the diverse range of the basal cAMP pool size in resting cells
      through mutual additive or suppressive interactions, even in the absence of
      external stimulation.

PMID- 29054410
TI  - Molecular cloning and 3D model of first cytochrome P450 from CYP3A subfamily in
      saltwater crocodile (Crocodylus porosus).
AB  - Cytochrome P450s (CYPs) play critical role in oxidative metabolism of numerous
      xenobiotics and endogenous compounds. The first CYP3A subfamily member in
      saltwater crocodile has been cloned and modelled for three-dimensional (3D)
      structure. The full-length cDNA was obtained employing reverse transcription
      polymerase chain reaction (RT-PCR) strategy and rapid amplification of cDNA ends
      (RACE). The cDNA sequence of 1659 nucleotides includes 132 nucleotides from 5'
      untranslated region (UTR), an open reading frame of 1527 nucleotides encoding 509
      amino acids designated as CYP3A163. The alignment of CYP3A163 sequence with CYP3A
      subfamily across the lineages exhibit the loss of 1 residue in birds and 7
      residues in mammals in comparison to reptiles suggesting the adaptation processes
      during evolution. The amino acid identity of CYP3A163 with Alligator
      mississippiensis CYP3A77 and Homo sapiens CYP3A4 is 91% and 62% respectively. The
      3D structure of CYP3A163 modelled using human CYP3A4 structure as a template with
      Phyre2 software, represents high similarity with its functionally important
      motifs and catalytic domain. Both sequence and structure of CYP3A163 display the
      common and conserved features of CYP3A subfamily. Overall, this study provides
      primary molecular and structural data of CYP3A163 required to investigate the
      xenobiotic metabolism in saltwater crocodiles.

PMID- 29054412
TI  - Regulatory mechanisms for iron transport across the blood-brain barrier.
AB  - Many critical metabolic functions in the brain require adequate and timely
      delivery of iron. However, most studies when considering brain iron uptake have
      ignored the iron requirements of the endothelial cells that form the blood-brain
      barrier (BBB). Moreover, current models of BBB iron transport do not address
      regional regulation of brain iron uptake or how neurons, when adapting to
      metabolic demands, can acquire more iron. In this study, we demonstrate that both
      iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate
      release of iron from iron-loaded endothelial cells in an in vitro BBB model. The
      role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition
      and transport has been questioned. Here, we show that inhibition of DMT1 alters
      the transport of iron and Tf across the endothelial cells. These data support an
      endosome-mediated model of Tf-bound iron uptake into the brain and identifies
      mechanisms for local regional regulation of brain iron uptake. Moreover, our data
      provide an explanation for the disparity in the ratio of Tf to iron transport
      into the brain that has confounded the field.

PMID- 29054411
TI  - E6AP/UBE3A catalyzes encephalomyocarditis virus 3C protease polyubiquitylation
      and promotes its concentration reduction in virus-infected cells.
AB  - The encephalomyocarditis virus (EMCV) 3C protease (3Cpro) is one of a small
      number of viral proteins whose concentration is known to be regulated by the
      cellular ubiquitin-proteasome system. Here we report that the ubiquitin
      conjugating enzyme UbcH7/UBE2L3 and the ubiquitin-protein ligase E6AP/UBE3A are
      components of a previously unknown EMCV 3Cpro-polyubiquitylating pathway.
      Following the identification of UbcH7/UBE2L3 as a participant in 3Cpro
      ubiquitylation, we purified a UbcH7-dependent 3Cpro-ubiquitylating activity from
      mouse cells, which we identified as E6AP. In vitro reconstitution assays
      demonstrated that E6AP catalyzes the synthesis of 3Cpro-attached Lys48-linked
      ubiquitin chains, known to be recognized by the 26S proteasome. We found that the
      3Cpro accumulates to higher levels in EMCV-infected E6AP knockdown cells than in
      control cells, indicating a role for E6AP in in vivo 3Cpro concentration
      regulation. We also discovered that ARIH1 functions with UbcH7 to catalyze EMCV
      3Cpro monoubiquitylation, but this activity does not influence the in vivo 3Cpro
      concentration.

PMID- 29054413
TI  - A 2 bp deletion in the mitochondrial ATP 6 gene responsible for the NARP
      (neuropathy, ataxia, and retinitis pigmentosa) syndrome.
AB  - Mitochondrial (mt) DNA-associated NARP (neurogenic muscle weakness, ataxia, and
      retinitis pigmentosa) syndrome is due to mutation in the MT-ATP6 gene. We report
      the case of a 18-year-old man who presented with deafness, a myoclonic epilepsy,
      muscle weakness since the age of 10 and further developed a retinitis pigmentosa
      and ataxia. The whole mtDNA analysis by next-generation sequencing revealed the
      presence of the 2 bp microdeletion m.9127-9128 del AT in the ATP6 gene at 82%
      heteroplasmy in muscle and to a lower load in blood (10-20%) and fibroblasts
      (50%). Using the patient's fibroblasts, we demonstrated a 60% reduction of the
      oligomycin-sensitive ATPase hydrolytic activity, a 40% decrease in the ATP
      synthesis and determination of the mitochondrial membrane potential using the
      fluorescent probe tetramethylrhodamine, ethyl ester indicated a significant
      reduction in oligomycin sensitivity. In conclusion, we demonstrated that this
      novel AT deletion in the ATP6 gene is pathogenic and responsible for the NARP
      syndrome.

PMID- 29054414
TI  - The Epidemiology of Selenium and Human Cancer.
AB  - The relation between selenium and cancer has been one of the most hotly debated
      topics in human health over the last decades. Early observational studies
      reported an inverse relation between selenium exposure and cancer risk.
      Subsequently, randomized controlled trials showed that selenium supplementation
      does not reduce the risk of cancer and may even increase it for some types,
      including advanced prostate cancer and skin cancer. An increased risk of diabetes
      has also been reported. These findings have been consistent in the most
      methodologically sound trials, suggesting that the early observational studies
      were misleading. Other studies have investigated selenium compounds as adjuvant
      therapy for cancer. Though there is currently insufficient evidence regarding the
      utility and safety of selenium compounds for such treatments, this issue is
      worthy of further investigation. The study of selenium and cancer is complicated
      by the existence of a diverse array of organic and inorganic selenium compounds,
      each with distinct biological properties, and this must be taken into
      consideration in the interpretation of both observational and experimental human
      studies.

PMID- 29054415
TI  - Selenium-Dependent Glutathione Peroxidases During Tumor Development.
AB  - Five out of eight human glutathione peroxidases (GPxes) are selenoproteins and
      thus their expression depends on the selenium (Se) supply. Most Se-dependent
      GPxes are downregulated in tumor cells, while only GPx2 is considerably
      upregulated. Whether expression profiles of GPxes predict tumor development and
      patient survival is controversially discussed. Also, results from in vitro and in
      vivo studies modulating the expression of GPx isoforms provide evidence for both
      anti- and procarcinogenic mechanisms. GPxes are able to reduce hydroperoxides,
      which otherwise would damage DNA, possibly resulting in DNA mutations, modulate
      redox-sensitive signaling pathways affecting proliferation, differentiation, and
      cellular metabolism or initiate cell death. Considering these different
      processes, the role and functions of individual Se-dependent GPx isoforms will be
      discussed herein in the context of tumorigenesis.

PMID- 29054416
TI  - Targeting the Selenoprotein Thioredoxin Reductase 1 for Anticancer Therapy.
AB  - The cytosolic selenoprotein thioredoxin reductase 1 (TrxR1, encoded in human by
      TXNRD1) is implied to have several different roles in relation to cancer. Its
      physiologic functions may protect normal cells from carcinogenesis, but may also
      promote cancer progression if carcinogenesis nonetheless occurs. With distinct
      links to Nrf2 signaling, ribonucleotide reductase-dependent production of
      deoxyribonucleotides and its support of several antioxidant systems counteracting
      oxidative stress, the metabolic pathways regulated, and affected by TrxR1, are
      altogether of crucial importance in cancer. These pathways and causal
      relationships are at the same time highly intricate. In spite of the complexity
      in the cellular redox networks, several observations discussed in this chapter
      suggest that specific targeting of TrxR1 may be promising as a mechanistic
      principle for anticancer therapy.

PMID- 29054418
TI  - Selenium and Breast Cancer Risk: Focus on Cellular and Molecular Mechanisms.
AB  - Selenium (Se) is a micronutrient with promising breast cancer prevention and
      treatment potential. There is extensive preclinical evidence of Se mammary
      carcinogenesis inhibition. Evidence from epidemiological studies is, however,
      unclear and intervention studies are rare. Here, we examine Se chemoprotection,
      chemoprevention, and chemotherapy effects in breast cancer, focusing on
      associated cellular and molecular mechanisms. Se exerts its protective actions
      through multiple mechanisms that involve antioxidant activities, induction of
      apoptosis, and inhibition of DNA damage, cell proliferation, angiogenesis, and
      invasion. New aspects of Se actions in breast cancer have emerged such as the
      impact of genetic polymorphisms on Se metabolism and response, new functions of
      selenoproteins, epigenetic modulation of gene expression, and long-term influence
      of early-life exposure on disease risk. Opportunity exists to design
      interventional studies with Se for breast cancer prevention and treatment taking
      into consideration these key aspects.

PMID- 29054419
TI  - Selenium and Epigenetics in Cancer: Focus on DNA Methylation.
AB  - Chemopreventive activity of selenium (Se) may influence epigenome. In this
      review, we have discussed two aspects of Se and epigenetics in cancer, related to
      (1) the association between Se and epigenetic regulation in cancer development
      and prevention; (2) epigenetic modification of selenoprotein-encoding genes in
      different cancers. In both issues, we focused on DNA methylation as the most
      investigated epigenetic mechanism. The existing evidence from experimental data
      in human cancer cell lines, rodents, and human studies in cancer-free subjects
      indicates that: high Se exposure leads to the inhibition of DNA methyltransferase
      expression/activity; the association between Se and global methylation remains
      unclear and requires further investigation with respect to the underlying
      mechanisms and possible nonlinear character of this relationship; Se affects
      methylation of specific tumor suppressor genes, possibly in a sex-dependent
      manner; and cancer phenotype is often characterized by altered methylation of
      selenoprotein-encoding genes, mainly glutathione peroxidase 3.

PMID- 29054417
TI  - The Regulation of Pathways of Inflammation and Resolution in Immune Cells and
      Cancer Stem Cells by Selenium.
AB  - Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited
      replicative potential, but evade chemotherapy drugs through cellular quiescence.
      CSCs are able to give rise to bulk tumor cells that have the capability to
      override antiproliferative signals and evade apoptosis. Numerous pathways are
      dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen
      and nitrogen species can lead to localized inflammation to exacerbate all three
      stages of tumorigenesis: initiation, progression, and metastasis. Modulation of
      cellular metabolism in tumor cells as well as immune cells in the tumor
      microenvironment (TME) can impact inflammatory networks. Altering these pathways
      can potentially serve as a portal for therapy. It is well known that selenium,
      through selenoproteins, modulates inflammatory pathways in addition to regulating
      redox homeostasis in cells. Therefore, selenium has the potential to impact the
      interaction between tumor cells, CSCs, and immune cells. In the sections later,
      we review the current status of knowledge regarding this interaction, with
      reference to leukemia stem cells, and the importance of selenium-dependent
      regulation of inflammation as a potential mechanism to affect the TME and tumor
      cell survival.

PMID- 29054420
TI  - Selenium and Cancer Stem Cells.
AB  - Selenium (Se) is an essential micronutrient that functions as "redox gatekeeper"
      and homeostasis factor of normal and cancer cells. Epidemiology and experimental
      studies, in the last years suggested that both inorganic and organic forms of Se
      may have favorable health effects. In this regard, a protective action of Se on
      cellular systems that may help preventing cancer cell differentiation has been
      demonstrated, while the hypothesis that Se compounds may cure cancer and its
      metastatic diffusion appears speculative and is still a matter of investigation.
      Indeed, the overall actions of Se compounds in carcinogenesis are controversial.
      The recognition that cancer is a stem cell disease instigated major paradigm
      shifts in our basic understanding of cancer and attracted a great deal of
      interest. Although current treatment approaches in cancer are grounded in the
      need to kill the majority of cancer cells, targeting cancer stem cells (CSCs) may
      hold great potential in improving cancer treatment. In this respect, Se compounds
      have been demonstrated modulating numerous signaling pathways involved in CSC
      biology and these findings are now stimulating further research on optimal Se
      concentrations, most effective and cancer-specific Se compounds, and inherent
      pathways involved in redox and metabolic regulation of CSCs. In this review, we
      summarize the current knowledge about the effects of Se compounds on CSCs, by
      focusing on redox-dependent pathways and main gene regulation checkpoints that
      affect self-renewal, differentiation, and migration responses in this
      subpopulation of cancer cells.

PMID- 29054421
TI  - Selenocompounds in Cancer Therapy: An Overview.
AB  - In vitro and in vivo experimental models clearly demonstrate the efficacy of Se
      compounds as anticancer agents, contingent upon chemical structures and
      concentrations of test molecules, as well as on the experimental model under
      investigation that together influence cellular availability of compounds, their
      molecular dynamics and mechanism of action. The latter includes direct and
      indirect redox effects on cellular targets by the activation and altered
      compartmentalization of molecular oxygen, and the interaction with protein thiols
      and Se proteins. As such, Se compounds interfere with the redox homeostasis and
      signaling of cancer cells to produce anticancer effects that include alterations
      in key regulatory elements of energy metabolism and cell cycle checkpoints that
      ultimately influence differentiation, proliferation, senescence, and death
      pathways. Cys-containing proteins and Se proteins involved in the response to Se
      compounds as sensors and transducers of anticancer signals, i.e., the
      pharmacoproteome of Se compounds, are described and include critical elements in
      the different phases of cancer onset and progression from initiation and escape
      of immune surveillance to tumor growth, angiogenesis, and metastasis. The
      efficacy and mode of action on these compounds vary depending on the inorganic
      and organic form of Se used as either supplement or pharmacological agent. In
      this regard, differences in experimental/clinical protocols provide options for
      either chemoprevention or therapy in different human cancers.

PMID- 29054424
TI  - Preface.

PMID- 29054423
TI  - Selenoproteins and Metastasis.
AB  - Cancer survival is largely impacted by the dissemination of cancer cells from the
      original tumor site to secondary tissues or organs through metastasis. Targets
      for antimetastatic therapies have recently become a focus of research, but
      progress will require a better understanding of the molecular mechanisms driving
      metastasis. Selenoproteins play important roles in many of the cellular
      activities underlying metastasis including cell adhesion, matrix degradation and
      migration, invasion into the blood and extravasation into secondary tissues, and
      subsequent proliferation into metastatic tumors along with the angiogenesis
      required for growth. In this review the roles identified for different
      selenoproteins in these steps and how they may promote or inhibit metastatic
      cancers is discussed. These roles include selenoenzyme modulation of redox tone
      and detoxification of reactive oxygen species, calcium homeostasis and unfolded
      protein responses regulated by endoplasmic reticulum selenoproteins, and the
      multiple physiological responses influenced by other selenoproteins.

PMID- 29054422
TI  - Selenoproteins in Tumorigenesis and Cancer Progression.
AB  - Selenium is a micronutrient essential to human health and has long been
      associated with cancer prevention. Functionally, these effects are thought to be
      mediated by a class of selenium-containing proteins known as selenoproteins.
      Indeed, many selenoproteins have antioxidant activity which can attenuate cancer
      development by minimizing oxidative insult and resultant DNA damage. However,
      oxidative stress is increasingly being recognized for its "double-edged sword"
      effect in tumorigenesis, whereby it can mediate both negative and positive
      effects on tumor growth depending on the cellular context. In addition to their
      roles in redox homeostasis, recent work has also implicated selenoproteins in key
      oncogenic and tumor-suppressive pathways. Together, these data suggest that the
      overall contribution of selenoproteins to tumorigenesis is complicated and may be
      affected by a variety of factors. In this review, we discuss what is currently
      known about selenoproteins in tumorigenesis with a focus on their contextual
      roles in cancer development, growth, and progression.

PMID- 29054425
TI  - Molecular characterization of congenital myasthenic syndromes in Spain.
AB  - Congenital myasthenic syndromes (CMS) are a heterogeneous group of genetic
      disorders, all of which impair neuromuscular transmission. Epidemiological data
      and frequencies of gene mutations are scarce in the literature. Here we describe
      the molecular genetic and clinical findings of sixty-four genetically confirmed
      CMS patients from Spain. Thirty-six mutations in the CHRNE, RAPSN, COLQ, GFPT1,
      DOK7, CHRNG, GMPPB, CHAT, CHRNA1, and CHRNB1 genes were identified in our
      patients, with five of them not reported so far. These data provide an overview
      on the relative frequencies of the different CMS subtypes in a large Spanish
      population. CHRNE mutations are the most common cause of CMS in Spain, accounting
      for 27% of the total. The second most common are RAPSN mutations. We found a
      higher rate of GFPT1 mutations in comparison with other populations. Remarkably,
      several founder mutations made a large contribution to CMS in Spain: RAPSN c.264C
      > A (p.Asn88Lys), CHRNE c.130insG (Glu44Glyfs*3), CHRNE c.1353insG
      (p.Asn542Gluf*4), DOK7 c.1124_1127dup (p.Ala378Serfs*30), and particularly
      frequent in Spain in comparison with other populations, COLQ c.1289A > C
      (p.Tyr430Ser). Furthermore, we describe phenotypes and distinguishing clinical
      signs associated with the various CMS genes which might help to identify specific
      CMS subtypes to guide diagnosis and management.

PMID- 29054427
TI  - Common brain networks for distinct deficits in visual neglect. A combined
      structural and tractography MRI approach.
AB  - Visual neglect is a heterogeneous, multi-component syndrome resulting from right
      hemisphere damage. Neglect patients do not pay attention to events occurring on
      their left side, and have a poor functional outcome. The intra-hemispheric
      location of lesions producing neglect is debated, because studies using different
      methods reported different locations in the grey matter and in the white matter
      of the right hemisphere. These reported locations show various patterns of
      overlapping with the fronto-parietal attention networks demonstrated by
      functional neuroimaging. We explored the anatomical correlates of neglect
      patients' performance on distinct tests of neglect. For the first time in neglect
      anatomy studies, we individually assessed 25 patients with subacute strokes in
      the right hemisphere, by using a combined structural and diffusion tensor
      deterministic tractography approach, with separate analyses for each neglect
      test. The results revealed that lesions in nodes of the ventral attention network
      (angular and supramarginal gyri) were selectively associated with deficits in
      performance on all the tests used; damage to other structures correlated with
      impaired performance on specific tests, such as the bells test (middle and
      inferior frontal gyri), or the reading test (temporal regions). Importantly,
      however, white matter damage proved crucial in producing neglect-related
      deficits. Voxel-based lesion-symptom mapping (VLSM) and tractography consistently
      revealed that damage to the ventral branch of the superior longitudinal
      fasciculus (SLF III) and to the inferior fronto-occipital fasciculus (IFOF)
      predicted pathological scores on line bisection/drawing copy and on the bells
      test, respectively. Moreover, damage to distinct sectors of SLF III, or combined
      SLF/IFOF damage, gave rise to different performance profiles. Our results
      indicate that both grey and white matter lesion analysis must be taken into
      account to determine the neural correlates of neglect-related deficits. They also
      suggest that damage to distinct portions of white matter tracts may give rise to
      distinct clinical signs of neglect, presumably by inducing dysfunction of partly
      overlapping, but distinct networks.

PMID- 29054426
TI  - Origin of the myotonic dystrophy type 1 mutation in Mexican population and
      influence of Amerindian ancestry on CTG repeat allelic distribution.
AB  - Myotonic dystrophy type 1 is caused by expansion of a CTG trinucleotide repeat
      situated in the DMPK gene. Worldwide genetic studies suggest a single or limited
      number of mutational events cause the disease. However, distribution of CTG
      alleles and disease incidence varies among ethnicities. Due to the great ethnic
      diversity of the Mexican population, the present study was aimed at analyzing the
      impact of different lineages in shaping the CTG-repeat allelic distribution in
      the contemporary Mexican-Mestizo population as well as to shed light on the DM1
      ancestral origin. Distribution of CTG-repeat alleles was similar among Mestizo
      and Amerindian subpopulations with (CTG)11-13 being the most frequent alleles in
      both groups, which implies that Mexican-Mestizo allelic distribution has been
      modeled by Amerindian ancestry. We diagnosed a relatively high number of cases,
      consistent with the high frequency of large-normal alleles found in Mexican
      subpopulations. Haplotype analysis using various polymorphic-markers in proximity
      to DMPK gene indicates that a single founder mutation originates myotonic
      dystrophy type 1 in Mexico; however, Y-STR haplogroups data and the presence of
      pre-mutated and large normal alleles in Amerindians support the hypothesis that
      both European and Amerindian ancestral chromosomes might have introduced the
      disease to the Mexican population, which was further disseminated through
      mestizaje.

PMID- 29054428
TI  - beta-Arrestin2 directly or through GRK2 inhibits PKCbetaII activation in a
      ubiquitination-dependent manner.
AB  - The GRK/beta-arrestin and PKC/PKA mediate the homologous and heterologous
      regulation of G protein-coupled receptors (GPCRs), respectively. Interaction
      between the two pathways is one of the most important issues in understanding the
      regulation of GPCRs. The present study investigated the regulatory effect of GRK2
      and beta-arrestins on PKC activation. The roles of GRK2 and beta-arrestins in the
      functional regulation of PKC were assessed by determining their influence on PKC
      autophosphorylation and intracellular translocation. Radioligand binding assay
      was utilized to characterize intracellular trafficking of dopamine D2R, D3R, and
      beta2 adrenergic receptor (beta2AR). The subdomains involved in the mutual
      interactions among GRK2, beta-arrestin2, and PKCbetaII were determined by in
      vitro binding assay. Various point mutants of key regulatory players were
      combined with knockdown cells of GRK2, beta-arrestins, and Mdm2 to functionally
      correlate the biochemical changes with functional outcomes. GRK2 and beta
      arrestin2 mutually inhibited the PKCbetaII autophosphorylation, a hallmark of
      PKCbetaII activation. beta-Arrestin2 ubiquitination was required for the
      inhibitory activities of GRK2 as well as beta-arrestin2. Furthermore, GRK2
      facilitated beta-arrestin2 ubiquitination, thus to enhance the inhibitory actions
      of beta-arrestin2 on PKCbetaII activity. Aforementioned processes were also
      involved in the GRK2/beta-arrestin2-mediated inhibition of the D2R, D3R, and
      beta2AR endocytosis. The present study provides new insights into the intricate
      interactions between the homologous and heterologous GPCR regulation pathways. In
      addition, a novel regulatory role of GRK2 was proposed for the ubiquitination of
      beta-arrestin in the context of the PKC-mediated heterologous regulation of
      GPCRs.

PMID- 29054430
TI  - NMDA receptor dependent changes in c-fos and p-CREB signaling following
      extinction and reinstatement of morphine place preference.
AB  - Neural circuitry comprising the ventral tegmental area, nucleus accumbens (NAc),
      prefrontal cortex (PFC) and hippocampus (HIP) has a main role in reward
      phenomena. Previous behavioral studies indicated that intracerebroventricular
      administration of AP5 (NMDA glutamate receptor antagonist) and CNQX (AMPA/kainate
      glutamate receptor antagonist) during the extinction and before reinstatement of
      morphine-induced conditioned place preference (CPP) reduced the extinction period
      and reinstatement of morphine-CPP. Therefore, in the present study, we tried to
      evaluate the effect of antagonism of NMDA glutamate receptors on the p-CREB/CREB
      ratio and c-fos expression in the NAc, PFC and HIP during these two phases of
      morphine-CPP in male adult albino Wistar rats. The p-CREB/CREB ratio and c-fos
      levels were estimated by Western blot analysis. The results revealed that these
      two factors decreased by antagonism of NMDA glutamate receptors (different doses
      of AP5) compared to saline-control group in aforementioned regions. The reduction
      of molecular markers, especially the p-CREB/CREB ratio, after AP5 administration
      was more during the extinction period. Therefore, it can be assumed that
      consolidation and reconsolidation of morphine memory via intra-PFC, -NAc and -HIP
      NMDA glutamate receptors are in accordance with changes in p-CREB/CREB ratio and
      c-fos levels.

PMID- 29054429
TI  - Surface chemistry induces mitochondria-mediated apoptosis of breast cancer cells
      via PTEN/PI3K/AKT signaling pathway.
AB  - Tumor cell can be significantly influenced by various chemical groups of the
      extracellular matrix proteins. However, the underlying molecular mechanisms
      involved in the interaction between cancer cells and functional groups in the
      extracellular matrix remain unknown. Using chemically modified surfaces with
      biological functional groups (CH3, NH2, OH), it was found that hydrophobic
      surfaces modified with CH3 and NH2 suppressed cell proliferation and induced the
      number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax
      upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that
      hydrophobic surfaces with CH3 and NH2 triggered the activation of intrinsic
      apoptotic signaling pathway. Cells on the CH3- and NH2-modified hydrophobic
      surfaces showed downregulated expression and activation of integrin beta1, with a
      subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN
      signaling was then activated to inhibit the phosphorylation of PI3K and AKT,
      which are essential for cell proliferation. However, pretreatment of MDA-MB-231
      cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced
      activation of the intrinsic pathway. Taken together, the present results indicate
      that CH3- and NH2-modified hydrophobic surfaces induce mitochondria-mediated
      apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These
      findings are helpful to understand the interaction between extracellular matrix
      and cancer cells, which might provide new insights into the mechanism potential
      intervention strategies for tumor prognosis.

PMID- 29054431
TI  - Lesions of the lateral habenula improve working memory performance in
      hemiparkinsonian rats.
AB  - The lateral habenula (LHb) is an important structure involved in various brain
      functions, because it controls the activity of dopaminergic and serotonergic
      systems in the midbrain. The impairment of working memory commonly occurs in
      Parkinson's disease; however, it is not clear whether the LHb involves in the
      regulation of working memory in rats with unilateral 6-hydroxydopamine lesions of
      the medial forebrain bundle (MFB). In this study, we found that the MFB lesions
      in rats decreased choice accuracy as measured by the T-maze rewarded alternation
      test compared to control rats, indicating the induction of working memory
      impairment, and decreased dopamine (DA) levels in the medial prefrontal cortex
      (mPFC), hippocampus and amygdala. Further, rats in the MFB and LHb lesion group
      showed increased choice accuracy compared to rats in the MFB lesion group,
      indicating the enhancement of working memory after lesioning the LHb.
      Neurochemical results found that lesions of the LHb increased DA levels in the
      mPFC, hippocampus and amygdala in the MFB and LHb lesion group, as well as
      serotonin (5-HT) level in the mPFC. These findings suggest that DA depletion
      plays a key role in working memory impairment, and lesions of the LHb improve
      working memory in the MFB-lesioned rats, which involves in increases in the
      levels of DA and 5-HT in the mPFC, hippocampus and amygdala. Additionally, the
      present results may have implications for improving our understanding of the
      neuropathology and/or treatment of PD.

PMID- 29054432
TI  - Expression pattern of EYA4 in the common marmoset (Callithrix jacchus) cochlea.
AB  - The eyes absent (EYA)-like genes are essential for the formation of sensory
      organs among fly (Drosophila melanogaster) and mammals. EYA4, one of the
      vertebrate genes of Eya family, is reported to be causative for late-onset mid
      frequency sensorineural hearing loss in humans, while Eya4-deficient mice
      exhibited congenital profound deafness and otitis media with effusion due to the
      eustachian tube dysmorphology. Because of the species difference in the
      phenotype, the pathophysiology of EYA4 in the human cochlea has yet to be
      elucidated. Here, we examine the expression pattern of EYA4 in the cochlea of
      common marmoset (Callithrix jacchus), a non-human primate. The results indicated
      a distinct expression pattern of EYA4 in the adult marmoset cochleae, especially
      strong in all supporting cells, while in mouse their expressions were diminished.
      Interestingly, EYA4 expression in the hair cells, supporting cells and neurons
      was co-localized with sine oculis homeobox-SIX1, a transcription factor essential
      for the transcriptional activity of EYA4. The results revealed inter-species
      differences in the expression pattern of EYA4 gene in supporting cells between
      primates and rodents. The results also indicated a fundamental role of EYA4 in
      the primate auditory cells. Experiments with primate models such as marmosets or
      with human cochlear cells may provide cues about the unknown pathogenesis of EYA4
      related hearing loss.

PMID- 29054433
TI  - Epilepsy: Advances in genetics and pathophysiology.

PMID- 29054434
TI  - Associations between single-nucleotide polymorphisms in the NTRK1 gene and basal
      pain sensitivity in young Han Chinese women.
AB  - OBJECTIVES: The NTRK1 gene plays an important role in sensory and sympathetic
      neuronal survival. Mutations in this gene cause a rare hereditary disease known
      as congenital insensitivity to pain with anhidrosis. The aim of this study was to
      explore possible associations between single-nucleotide polymorphisms (SNPs) in
      NTRK1 and pain perception in a selected population. METHODS: A total of 309
      healthy Han Chinese female undergraduates were recruited. Responses to
      quantitative sensory testing of pressure pain (dull, sharp, and acupuncture) were
      assessed, and genotyping of 13 tag-SNPs of NTRK1 was performed in the
      undergraduates recruited. Association analyses were performed via logistic
      regression analysis after adjusting for covariates such as age and body mass
      index. Promising associations were replicated in 197 patients scheduled to
      undergo gynecological surgery. RESULTS: The results showed that nine tag-SNPs of
      NTRK1 were significantly associated with pressure pain thresholds (P<0.05),
      leading to either hypersensitivity or hyposensitivity. More specifically, four
      tag-SNPs, rs1800880, rs6334, rs2644604 and rs943552, revealed a highly
      significant (P=0.008, 0.02, 0.01, 0.01, respectively) association with lower
      mechanical pain sensitivity of sharp pressure pain. Individuals who carried the
      haplotype CTCC were hyposensitive to sharp pressure pain compared with other
      haplotypes. CONCLUSION: These results suggest that polymorphisms in NTRK1 play an
      important role in pain sensitivity in young Han Chinese women.

PMID- 29054435
TI  - Networks of phobic fear: Functional connectivity shifts in two subtypes of
      specific phobia.
AB  - Anxiety disorders can be conceptualized by an abnormal interplay of emotion
      processing brain circuits; however, knowledge of brain connectivity measures in
      specific phobia is still limited. To explore functional interactions within
      selected fear-circuitry structures (anterior cingulate cortex (ACC), amygdala,
      insula), we re-examined three task-based fMRI studies using a symptom provocation
      approach (n=94 subjects in total) on two different phobia subtypes (animal
      subtype as represented by snake phobia (SP) and blood-injection-injury subtype as
      represented by dental phobia (DP)), and a non-phobic healthy control group (HC).
      Functional connectivity (FC) analyses detected a negative coupling between the
      amygdala and the ACC in HC for both classes of phobic stimuli, while SP and DP
      lacked this inhibitory relationship during visual stimulus presentation. However,
      a negative FC between the insula and the amygdala was observed in DP during
      visual symptom provocation, which reversed to a positive FC under auditory
      symptom provocation pointing to effects depending on stimulus modality in DP. SP
      showed significantly higher FC towards snake-anxiety eliciting stimuli than HC on
      an average measure of FC, while DP showed a similar pattern under auditory
      stimulation only. These findings altogether indicate FC shifts during symptom
      provocation in specific phobia possibly reflecting impaired emotion regulation
      processes within fear-circuitry networks. FC hence could represent a prime target
      for neuroscience-informed augmentation strategies when treating pathological
      forms of fear.

PMID- 29054436
TI  - In vitro and ex vivo screening of candidate therapeutics to restore
      neurotransmission in nerve terminals intoxicated by botulinum neurotoxin serotype
      A1.
AB  - Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that
      block cholinergic release in the peripheral nervous system and cause death by
      asphyxiation. While post-exposure prophylaxis can effectively eliminate toxin in
      the bloodstream, there are no clinically effective treatments to prevent or
      reverse disease once BoNT has entered the neuron. To address the need for post
      symptomatic countermeasures, we designed and developed an in vitro assay based on
      whole-cell, patch-clamp electrophysiological monitoring of miniature excitatory
      post-synaptic currents in synaptically active murine embryonic stem cell-derived
      neurons. This synaptic function-based assay was used to assess the efficacy of
      rationally selected drugs to restore neurotransmission in neurons comprehensively
      intoxicated by BoNT/A. Based on clinical reports suggesting that elevated Ca2+
      signaling promotes symptomatic relief from botulism, we identified seven
      candidate drugs that modulate presynaptic Ca2+ signaling and assessed their
      ability to reverse BoNT/A-induced synaptic blockade. The most effective drugs
      from the screen were found to phasically agonize voltage-gated calcium channel
      (VGCC) activity. Lead candidates were then applied to ex vivo studies in BoNT/A
      paralyzing mouse phrenic nerve-hemidiaphragm (PND) preparations. Treatment of
      PNDs with VGCC agonists after paralytic onset transiently potentiated nerve
      elicited muscle contraction and delayed progression to neuromuscular failure.
      Collectively, this study suggests that Ca2+-modulating drugs represent a novel
      symptomatic treatment for neuromuscular paralysis following BoNT/A poisoning.

PMID- 29054437
TI  - Method optimization for drug impurity profiling in supercritical fluid
      chromatography: Application to a pharmaceutical mixture.
AB  - A supercritical chromatographic method for the separation of a drug and its
      impurities has been developed and optimized applying an experimental design
      approach and chromatogram simulations. Stationary phase screening was followed by
      optimization of the modifier and injection solvent composition. A design-of
      experiment (DoE) approach was then used to optimize column temperature, back
      pressure and the gradient slope simultaneously. Regression models for the
      retention times and peak widths of all mixture components were built. The factor
      levels for different grid points were then used to predict the retention times
      and peak widths of the mixture components using the regression models and the
      best separation for the worst separated peak pair in the experimental domain was
      identified. A plot of the minimal resolutions was used to help identifying the
      factor levels leading to the highest resolution between consecutive peaks. The
      effects of the DoE factors were visualized in a way that is familiar to the
      analytical chemist, i.e. by simulating the resulting chromatogram. The mixture of
      an active ingredient and seven impurities was separated in less than eight
      minutes. The approach discussed in this paper demonstrates how SFC methods can be
      developed and optimized efficiently using simple concepts and tools.

PMID- 29054438
TI  - Applications of ionic liquids in biphasic separation: Aqueous biphasic systems
      and liquid-liquid equilibria.
AB  - Ionic liquids (ILs) have been receiving much attention in many fields of
      analytical chemistry because of their various interesting properties which
      distinguish them from volatile organic compounds. They offer both directional and
      non-directional forces towards a solute molecule and therefore act as excellent
      solvents for a wide range of polar and non-polar compounds. Because of the
      presence of various possible interactions, ILs easily undergo biphasic separation
      with water and other less polar/non-polar organic solvents. Their ability to
      create biphasic splitting makes them a promising candidate for liquid-liquid
      separation processes, such as aqueous biphasic systems and liquid-liquid
      equilibria. Various aspects of ILs in these separation methods are discussed in
      view of the origin of physical forces responsible for the biphasic interactions,
      the effect of structural components, temperature, pressure, pH and additives. The
      specific advantages of using ILs in aqueous biphasic systems and liquid-liquid
      equilibria in binary and ternary systems are discussed with a view to defining
      their future role in separation processes by giving major emphasis on developing
      non-toxic ILs with physical and solution properties tailored to the needs of
      specific sample preparation techniques.

PMID- 29054439
TI  - Effect of storage time, temperature, antioxidant and thawing on fatty acid
      composition of plasma, serum and red blood cells - A pilot biobank study.
AB  - BACKGROUND: It studies on the factors that affect the stability of fatty acid
      profiles from human blood specimens are generally performed by evaluating the
      effect of a single factor on an individual fatty acid and excluding a
      considerable amount of data from the total fatty acid profiles. METHODS: The
      stability of fatty acids from plasma, serum and red blood cells (RBC) was
      evaluated in terms of time, temperature, antioxidant and thawing. The fatty acids
      were methylated and analyzed by gas chromatography. The large volume of data is
      evaluated simultaneously and automatically by observing an Excel-based colour
      scale that indicates whether the fatty acid profiles have changed significantly
      as a result of the storage time (0-52weeks), temperature (-20 degrees C/-80
      degrees C), butylated hydroxytoluene (BHT) antioxidant (presence/absence) or
      thawing (single/multiple). RESULTS: Fatty acids from plasma were stable at both
      temperatures (-20 degrees C/-80 degrees C) regardless of BHT. Fatty acids from
      serum without BHT degrades faster at -80 degrees C than -20 degrees C and fatty
      acids from RBC without BHT degrades faster at -20 degrees C than -80 degrees C.
      Addition of BHT inhibits this effect in serum and RBC. Multiple thawing of RBC
      without BHT demonstrated that polyunsaturated fatty acids were generally more
      susceptible for changes at -80 degrees C than at -20 degrees C while BHT prevents
      partially this effect. CONCLUSIONS: This study draws attention to the importance
      of pre-analytical considerations when storing blood samples in biobanks and the
      need of careful judgments when analyzing fatty acids profiles.

PMID- 29054440
TI  - External validation of heart-type fatty acid binding protein, high-sensitivity
      cardiac troponin, and electrocardiography as rule-out for acute myocardial
      infarction.
AB  - OBJECTIVE: To externally validate a clinical decision rule incorporating heart
      fatty acid binding protein (h-FABP), high-sensitivity troponin (hs-cTn) and
      electrocardiogram (ECG) for the detection of acute myocardial infarction (AMI) on
      presentation to the Emergency Department. We also investigated whether this
      clinical decision rule improved identification of AMI over algorithms
      incorporating hs-cTn and ECG only. DESIGN AND METHODS: This study included data
      from 789 patients from the Brisbane ADAPT cohort and 441 patients from the
      Christchurch TIMI RCT cohort. The primary outcome was index AMI. Sensitivity,
      specificity, positive predictive value and negative predictive value were used to
      assess the diagnostic accuracy of the algorithms. RESULTS: 1230 patients were
      recruited, including 112 (9.1%) with AMI. The algorithm including h-FABP and hs
      cTnT had 100% sensitivity and 32.4% specificity. The algorithm utilising h-FABP
      and hs-cTnI had similar sensitivity (99.1%) and higher specificity (43.4%). The
      hs-cTnI and hs-cTnT algorithms without h-FABP both had a sensitivity of 98.2%; a
      result that was not significantly different from either algorithm incorporating h
      FABP. Specificity was higher for the hs-cTnI algorithm (68.1%) compared to the hs
      cTnT algorithm (33.0%). The specificity of the algorithm incorporating hs-cTnI
      alone was also significantly higher than both of the algorithms incorporating h
      FABP (p<0.01). CONCLUSION: For patients presenting to the Emergency Department
      with chest pain, an algorithm incorporating h-FABP, hs-cTn and ECG has high
      accuracy and can rule out up to 40% of patients. An algorithm incorporating only
      hs-cTn and ECG has similar sensitivity and may rule out a higher proportion of
      patients. Each of the algorithms can be used to safely identify patients as low
      risk for AMI on presentation to the Emergency Department.

PMID- 29054441
TI  - Diagnostic value of alpha-1-fetoprotein (AFP) as a biomarker for hepatocellular
      carcinoma recurrence after liver transplantation.
AB  - BACKGROUND: Alpha-1-fetoprotein (AFP) is used to monitor progression, evaluate
      response to therapy and predict recurrence of hepatocellular carcinoma (HCC) in
      liver transplantation (LTx) patients. To date, the diagnostic value of serum AFP
      determinations for detecting tumor recurrence in HCC patients after LTx is
      unclear. OBJECTIVE: A retrospective, single-center, cross-sectional, non
      interventional study was performed with the objective of determining post
      transplant cut-off AFP values for detecting HCC recurrence post LTx. METHODS:
      Using receiver operating characteristic (ROC) analyses, post-transplant serum AFP
      values were evaluated against HCC recurrences in 63 HCC patients who had LTx
      between November 1995 and December 2011 at the University Medical Center
      Gottingen (UMG). Optimal and application-independent cut points for predicting
      tumor recurrence at 1, 3, and 5years after LTx were determined. RESULTS: Post-LTx
      serum AFP was found to represent an independent risk factor (predictor) for HCC
      relapse. Post-operative AFP cut-off values of 7MUg/l, 6MUg/l, and 6MUg/l,
      respectively, were determined to be optimal at 1, 3, and 5years after LTx
      respectively for predicting a HCC relapse. Using these cut-off values, patients
      were correctly classified as relapse-positive with a diagnostic sensitivity of
      79%, 81%, and 77%, and as relapse-free with a specificity of 82%, 79%, and 69%.
      The diagnostic accuracy measured by area under the curve (AUC) values ranged from
      0.813 to 0.886. However, a limitation is that at a clinically relevant
      specificity of >=95%, the analyses showed sensitivity values of only 50%, 52%,
      and 50%, respectively. CONCLUSION: Post-transplant serum AFP may have diagnostic
      value to detect HCC recurrence after LTx.

PMID- 29054442
TI  - Approaches to hand hygiene monitoring: From low to high technology approaches.
AB  - Hand hygiene is a global and critical infection prevention practice across all
      healthcare settings. Approaches to monitoring hand hygiene compliance vary from
      simple methods such as direct observation and product usage to more advanced
      methods such as automated electronic monitoring systems. Current literature
      supports a multimodal approach, supplemented by education, to enhance hand
      hygiene performance.

PMID- 29054443
TI  - Development of an xTAG-multiplex PCR array for the detection of four avian
      respiratory viruses.
AB  - Acute respiratory tract infections are of paramount importance in the poultry
      industry. We developed an xTAG bead assay for the simultaneous detection and
      discrimination of avian influenza virus (AIV), Newcastle disease virus (NDV),
      infectious bronchitis virus (IBV) and infectious laryngotracheitis virus (ILTV).
      The assay lacked nonspecific reactions with other common avian viruses and the
      limit of detection was 6.75 * 102- 3.52 * 103copies/MUL. We examined 60 clinical
      specimens and found 18 positive for respiratory viruses. Our result demonstrated
      that xTAG-multiplex PCR method is a high-throughput, rapid, specific and
      sensitive assay for use in epidemiological studies and clinical detection of
      avian respiratory pathogens.

PMID- 29054444
TI  - Does audience affect the structure of warble song in budgerigars (Melopsittacus
      undulatus)?
AB  - In many bird species, male song functions both to defend a territory against
      other males and to attract a female mate. Male budgerigars (Melopsittacus
      undulatus) produce a song-like vocal signal, the warble, that can be directed at
      either females or other males. Warble is a long, complex, low amplitude, and
      variable vocalization composed of different element types. While there is some
      evidence that warble can induce reproduction, the function of this signal is
      largely uncertain and it is unclear whether male- and female-directed warble
      differ in either function or structure. We recorded male budgerigars in the
      presence of either their mate or a familiar male to identify whether the warbles
      produced with different audiences differed in structure. We dissected each warble
      into specific element units, classified units into a limited number of types by
      rule-based visual classification and calculated the proportion of each element
      type, element diversity, and total duration for the male- and female-directed
      warbles of each male. We also examined the sequential organization of warble
      element types (syntax) using time-window lagged sequential analysis. We found no
      differences in the proportions of different elements used, element diversity or
      duration of warbles between male- and female-directed warble. The syntax of
      warbles is similar when directed at males or females. However, we found greater
      between-individual similarity in the sequential organization of warbles directed
      towards females than in those directed towards males. The greater syntactical
      consistency in female-directed warble suggests that females may prefer either
      specific types of element sequences, or consistency itself, and thus shape the
      organization of warbles.

PMID- 29054445
TI  - Discussion of: "Endostapler versus Hem-O-Lok clip to secure the appendiceal stump
      and mesoappendix during laparoscopic appendectomy".

PMID- 29054446
TI  - Discussion of: "Laparoscopic common bile duct exploration versus endoscopic
      retrograde cholangiopancreatography for choledocholithiasis found at time of
      laparoscopic cholecystectomy: Analysis of a large integrated health care system
      database".

PMID- 29054447
TI  - Deletion of Mst1 attenuates neuronal loss and improves neurological impairment in
      a rat model of traumatic brain injury.
AB  - Neuronal cell death following traumatic brain injury (TBI) is a considerable
      contributor to neurological deficits. In our work, we explored the functions of
      Mammalian STE20-like kinase-1 (Mst1), a apoptosis-promoting kinase and also a
      pivotal bridgebuilder of apoptotic signaling, in the etiopathogenesis of an
      experimental rat model of TBI. We found that the phosphorylation level of Mst1 in
      injured area was significantly increased after TBI. Furthermore, we discovered
      that inhibition of Mst1 phosphorylation can effectively reduce neuronal cell
      death by inhibiting the activation of caspase 3 and suppressing the damage of DNA
      during TBI. In addition, the decreased of Mst1 phosphorylation level, not only
      reduced brain edema and blood-brain barrier (BBB) damage in injured region but
      also weakened the impairment of neurologic behavior during TBI. In conclusion,
      our work demonstrates that Mst1 plays an important role in TBI-induced neuronal
      cell death, suggesting that Mst1 is expected to be a potential therapeutic target
      for TBI.

PMID- 29054448
TI  - Brain ischemia: CT and MRI techniques in acute ischemic stroke.
AB  - Imaging plays a central role for intravenous and intra-arterial arterial ischemic
      stroke treatment patient selection. Computed tomography (CT) / CT angiography or
      magnetic resonance (MR) / MR angiography imaging are used to exclude stroke
      mimics and haemorrhage, to determine the cause and mechanism of stroke, to define
      the extension of brain infarct and to identify the arterial occlusion. Imaging
      may identify the patients that will be benefit more from revascularization
      therapies independently of the conventional therapeutic time window allowing
      individualized treatment decisions and improving individual patient outcome.
      Multiparametric CT/MR imaging may be used to identify the extension of potential
      viable brain tissue (penumbra) and of irreversible brain lesion (core) using CT
      perfusion and/or diffusion weighed and perfusion weighted MR imaging. The status
      of the arterial collateral circulation and the type and extension of the clot may
      be assessed by imaging. The accuracy and the clinical significance for treatment
      and patient clinical outcome of different imaging techniques are reviewed.

PMID- 29054449
TI  - Construction of infectious clones of lychnis ringspot virus and evaluation of its
      relationship with barley stripe mosaic virus by reassortment of genomic RNA
      segments.
AB  - Lychnis ringspot virus (LRSV, genus Hordeivirus) was first isolated in 1959, and
      has been shown to infect several dicot plants in nature. However, due to the lack
      of infectious cDNA clones, the biological properties and mechanisms underlying
      LRSV infection are obscure. In this work, we constructed infectious cDNA clones
      of LRSV and have compiled the complete LRSV genomic (g) RNA sequence. Comparison
      of nucleotide and amino acid sequences between LRSV and barley stripe mosaic
      virus (BSMV), the type member of genus Hordeivirus, reveals that despite
      belonging to the same genus, and replicating in chloroplasts, the viruses are
      only distantly related. This could be further indicated by the failure of
      different LRSV/BSMV reassortants to infect N. benthamiana. LRSV infectious cDNA
      clones provide a useful tool for studies of biological diversity among
      hordeiviruses, and also may contribute to the understanding of seed transmission
      in dicot plants.

PMID- 29054450
TI  - A portable precision ionization chamber: The transfer ionization reference
      chamber.
AB  - A portable instrument was developed at the Institute of Radiation Physics (IRA)
      for on-site radionuclides measurements. It will enable the measurement of short
      lived radionuclides in nuclear medicine departments or isotope production
      centres. The system involves an ionization chamber read directly by an
      electrometer and it was optimized to ensure a good reproducibility through the
      selection of an appropriate vial, filling volume and source position in the well
      chamber, as well as monitoring the external background and performing a detailed
      uncertainty estimation. The calibration factors were determined using solutions
      whose activity concentration is traceable to the international reference system
      using the IRA reference chamber. Currently the transfer ionization chamber is
      calibrated for F-18, C-11, O-15, N-13, I-131 and Tc-99m. The final instrument is
      able to measure isotope activities with a relative standard uncertainty not
      larger than 1%.

PMID- 29054451
TI  - Phenolic alkaloid oleracein E attenuates oxidative stress and neurotoxicity in
      AlCl3-treated mice.
AB  - AIMS: Chelation therapy and antioxidant supplements have been demonstrated to be
      useful in ameliorating aluminum (Al) induced neurotoxicity. Oleracein E (OE) is a
      phenolic antioxidant alkaloid which possesses a rare
      tetrahydroisoquinoline/pyrrolidone tricyclic skeleton and a catechol moiety. The
      aim of this study was to investigate whether OE can chelate with Al and alleviate
      AlCl3-induced oxidative stress and neurotoxicity. MAIN METHODS: Kunming mice were
      administered AlCl3 (40mg/kg/d, i.p., 28days), with co-administration of OE
      (3mg/kg/d, 15mg/kg/d, i.g.) and the positive control piracetam (PA, 400mg/kg/d,
      i.g.). The Al contents in the brain and plasma were determined using ICP-MS. Al
      chelating ability of OE was assayed using UV spectroscopy. MDA, GSH, SOD or CAT,
      in the brain or plasma were determined. HE staining was used to examine
      hippocampal morphology alterations. IHC staining was employed to measure the
      expression of apoptotic-related proteins Bax, Bcl-2 and Caspase-3. KEY FINDINGS:
      AlCl3 remarkably increased the brain and plasma Al contents, increased lipid
      peroxidation and induced hippocampal neuronal damage. OE chelated with Al to form
      a stable complex. An increase in brain Al content by OE (15mg/kg) likely occurred
      through chelating with Al, which reduced the toxicity of free Al ion in the
      brain. OE significantly decreased MDA by regulating some antioxidant biomarkers.
      Furthermore, OE significantly ameliorated the protein expression changes in some
      apoptotic indices induced by AlCl3. SIGNIFICANCE: The phenolic alkaloid OE, as an
      antioxidant, Al chelator and apoptosis inhibitor, alleviates oxidative stress and
      neurotoxicity induced by AlCl3.

PMID- 29054452
TI  - Mechanism of aquaporin 4 (AQP 4) up-regulation in rat cerebral edema under
      hypobaric hypoxia and the preventative effect of puerarin.
AB  - AIM: We aim to investigate the mechanism of aquaporin 4 (AQP 4) up-regulation
      during high-altitude cerebral edema (HACE) in rats under hypobaric hypoxia and
      preventative effect of puerarin. METHODS: Rats were exposed to a hypobaric
      chamber with or without the preventative treatment of puerarin or dexamethasone.
      Morriz water maze was used to evaluate the spatial memory injury. HE staining and
      W/D ratio were used to evaluate edema injury. Rat astrocytes and microglia were
      co-cultured under the condition of hypoxia with the administration of p38
      inhibitor, NF-kappaB inhibitor or puerarin. Interleukin 6 (IL-6) and tumor
      necrosis factor alpha (TNF alpha) of cortex and culture supernatant were measured
      with ELISA. AQP4, phosphorylation of MAPKs, NF-kappaB pathway of cortex and
      astrocytes were measured by Western blot. KEY FINDINGS: Weakened spatial memory
      and cerebral edema were observed after hypobaric hypoxia exposure. AQP4,
      phosphorylation of NF-kappaB and MAPK signal pathway of cortex increased after
      hypoxia exposure and decreased with preventative treatment of puerarin. Hypoxia
      increased TNF-alpha and IL-6 levels in cortex and microglia and puerarin could
      prevent the increase of them. AQP4 of astrocytes increased after co-cultured with
      microglia when both were exposed to hypoxia. AQP4 showed a decrease after
      administered with p38 inhibitor, NF-kappaB inhibitor or puerarin. SIGNIFICANCE:
      Hypoxia triggers inflammatory response, during which AQP4 of astrocytes can be up
      regulated through the release of TNF-alpha and IL-6 from microglia. Puerarin can
      exert a preventative effect on the increase of AQP4 through inhibiting the
      release of TNF-alpha and phosphorylation of NF-kappaB, MAPK pathway.

PMID- 29054454
TI  - Senescent hepatocyte secretion of matrix metalloproteinases is regulated by
      nuclear factor-kappaB signaling.
AB  - AIMS: Cellular senescence and matrix metalloproteinases (MMPs) play an important
      role in liver diseases. The source and regulating factors of MMPs in senescent
      hepatocytes are not known. We investigated whether senescent hepatocytes secreted
      MMPs and if this was regulated by nuclear factor (NF)-kappaB. MATERIALS AND
      METHODS: The TGF-alpha transgenic mouse hepatocyte line AML12 was treated with
      H2O2 to induce senescence. NF-kappaB signaling was examined by Western blotting
      and luciferase reporter assays. Quantitative reverse transcription polymerase
      chain reaction was used to evaluated expression of MMP-2, -9 and -13. KEY
      FINDINGS: AML12 cells treated with H2O2 showed the characteristic morphology of
      senescence. The activity of NF-kappaB and expression of MMP-2, -9 and -13 were
      increased in senescent AML12 cells. The NF-kappaB inhibitor BAY 11-7082 decreased
      the levels of MMPs. SIGNIFICANCE: These results suggest that senescent
      hepatocytes are involved in the pathology of liver diseases through remodeling
      the extracellular matrix.

PMID- 29054453
TI  - Disruption of dopamine D1/D2 receptor complex is involved in the function of
      haloperidol in cardiac H9c2 cells.
AB  - AIMS: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor
      (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it
      increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism
      of haloperidol action on cardiomyocytes through dopaminergic signaling was not
      described yet. This study investigated a role of dopamine receptors in
      haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological
      effect of melperone and haloperidol on basic heart parameters in rats. MATERIALS
      AND METHODS: We used differentiated NG-108 cells and H9c2 cells. Gene expression,
      Western blot and immunofluorescence were used to evaluate haloperidol-induced
      differences; proximity ligation assay (PLA) and immunoprecipitation to determine
      interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino
      male rats were used. KEY FINDINGS: We have shown that antagonism of D2R with
      either haloperidol or melperone results in upregulation of both, IP3R1 and Sig1R,
      which is associated with increased D2R, but reduced D1R expression.
      Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric
      D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone)
      caused decrease in systolic and diastolic blood pressure and significant increase
      in heart rate. SIGNIFICANCE: Because D1R/D2R complexes can engage Gq-like
      signaling in other experimental systems, these results are consistent with the
      possibility that disruption of D1R/D2R complex in H9c2 cells might cause a
      decrease in IP3R1 activity, which in turn may account for the increase expression
      of IP3R and Sig1R. D2R is probably not responsible for changes in cardiac
      parameters, since melperone did not have any effect.

PMID- 29054456
TI  - From locations to networks: Can brain imaging inform treatment of stuttering?

PMID- 29054455
TI  - DADLE enhances viability and anti-inflammatory effect of human MSCs subjected to
      'serum free' apoptotic condition in part via the DOR/PI3K/AKT pathway.
AB  - AIM: Nutritional deprivation and inflammation-rich zones are the major causative
      reasons for poor survivability of transplanted mesenchymal stem cells (MSCs).
      Therefore in the present study, we demonstrated the cytoprotective and anti
      inflammatory effects of activated delta (delta)-opioid receptor (DOR) with
      synthetic peptide [D-Ala2, D-Leu5]-enkephalin (DADLE) treatment on human MSCs
      cultured in serum-starved condition. MAIN METHODS: Cell viability was measured
      using MTT and Annexin V/PI assays. Expressions of pro-apoptotic (Bcl2) and anti
      apoptotic genes (Bax/Bad), levels of activated p44/42 MAPK, Akt, PI3-kinase
      p110gamma and cleaved caspase-3 were determined by qPCR and western blot. Levels
      of secreted cytokines were measured by ELISA. KEY FINDINGS: In comparison to the
      control, DADLE significantly increased cell survivability under serum deprived
      condition as confirmed by MTT (71% vs 45%) and Annexin V/PI assays (25.9% vs
      3.7%). Significant up-regulation of pro-apoptotic Bcl2 (~2.1 folds), down
      regulations of anti-apoptotic Bax/Bad (~2.6/2.7 folds) as well as of cleaved
      caspase-3, increased expression of PI3kinase subunit p110gamma and activation of
      Akt (Ser473) were observed following DADLE treatment in cells under 'serum
      deprivation' stress. In addition, DADLE treated hMSCs secreted increased levels
      of anti-inflammatory cytokines (IL10/IL4/TGF-beta) under serum deprived
      condition. LPS stimulated macrophages showed abated release of pro-inflammatory
      cytokines (IL1/TNFalpha/IL6) when grown in hMSC conditioned 'serum deprived'
      media treated with DADLE. Both the cytoprotective and anti-inflammatory effects
      of DADLE were inhibited by the DOR specific antagonist naltrindole. SIGNIFICANCE:
      The DOR signaling pathway improved cell viability and enhanced anti-inflammatory
      effect of hMSCs subjected to 'serum deprivation' stress that could have potential
      therapeutic benefits in reparative medicine.

PMID- 29054457
TI  - Bilateral vocal cord immobility resulting from cytomegalovirus pharyngitis: A
      case report.
AB  - Human cytomegalovirus (CMV) is an infectious herpes virus present in
      approximately 50% of the world's population. Pharyngitis is an uncommon
      manifestation of CMV infection, and vocal cord immobility (VCI) following CMV
      pharyngitis is quite rare. An 83-year-old man with well-controlled diabetes
      mellitus and hypertension was admitted due to dyspnea, odynophagia, and
      dysphagia. Laryngeal fiberscopy revealed bilateral vocal cords almost fixed at
      the median position, with mucosal redness, swelling, and edema at the
      hypopharyngeal area. The airway was so narrowed that an emergency tracheostomy
      was performed to secure an airway. VCI resulting from a malignant tumor was
      suspected at first, but repeated pathological examinations revealed CMV infection
      in the pharyngeal mucosa. Despite intravenous ganciclovir treatment (5 mg/kg),
      the patient's bilateral VCI improved only slightly. Laryngeal electromyography
      was used to investigate the causes of VCI, and revealed vocal fold paralysis on
      the left side and cricoarytenoid joint fixation on the right side. This case
      highlights the importance of considering CMV infection in the differential
      diagnosis of patients with pharyngitis and VCI. To the best of our knowledge,
      this is the first case report describing the etiology of VCI following CMV
      pharyngitis using laryngeal electromyography.

PMID- 29054458
TI  - Dosing optimization of meropenem based on a pharmacokinetic analysis in patients
      receiving hemodiafiltration and an in vitro model.
AB  - The purpose of this study was to estimate the in vivo pharmacokinetics of
      meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its
      optimal dosage and dosing interval in patients receiving I-HDF. The clearance of
      meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an
      in vitro system and assessed to establish whether the results obtained are
      applicable to clinical cases. In the in vivo study, the mean volume of
      distribution (Vd), non-I-HDF clearance (CLnon-I-HDF), and I-HDF clearance (CLI
      HDF) were 15.80 +/- 3.59 l, 1.05 +/- 0.27 l/h, and 5.78 +/- 1.03 l/h. Dosing
      regimens of 0.25 g once daily for a MIC of 8 MUg/ml and of 0.5 g once daily for a
      MIC of 16 MUg/ml achieved 40% T > MIC. In the in vitro and in vivo studies,
      observed CLHDF was similar to predictive CLHDF (= Cf/Cp * (QD + QSUB)). In
      conclusion, adjustments to the dose and interval of meropenem were developed
      based on the presumed susceptibility of pathogens to meropenem in patients
      receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for
      empirical treatment.

PMID- 29054460
TI  - [What is the European Code against Cancer, who knows it and why it serves?]

PMID- 29054459
TI  - Lymphocyte subset analysis in QuantiFERON-TB Gold Plus and T-Spot.TB for latent
      tuberculosis infection in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an immune mediated inflammatory disorder, and immune
      suppressive drugs are prescribed. RA patients receiving treatments are in a kind
      of immunosuppressive condition that presents increased risk of developing active
      tuberculosis. Accurate diagnosis of latent tuberculosis infection (LTBI) is
      recommended for RA. QuantiFERON(r)-TB Gold Plus (QFT-Plus), a novel IGRA, has two
      tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses,
      with expected increased sensitivity. We conducted a cross-sectional study to
      compare two IGRAs, QFT-Plus and T-SPOT(r).TB (TSPOT), in RA. One hundred fifty
      two RA patients (median age: 66.5 yrs) were enrolled. QFT-Plus and TSPOT were
      concurrently conducted. Lymphocyte subsets (CD4 T-cell and CD8 T-cell) were also
      measured. The positivity rates of QFT-Plus and TSPOT were 9.7% and 4.5%,
      respectively, with the difference being significant (P < 0.01). The positivity
      rates in TB1 and TB2 were 9.1% and 7.1%, respectively; the difference was not
      significant (P = 0.18). Patients with CD4 T-cell >=650/MUL and CD8 T-cell
      >=400/MUL had significantly higher positivity rates in both QFT-Plus and TSPOT in
      comparison with other groups (P < 0.01 and P < 0.05, respectively). QFT-plus
      demonstrated a higher positivity rate than TSPOT. However, there was little
      additional effect for detecting LTBI by TB2. Lymphocyte subsets were strongly
      associated with immune response in both QFT-Plus and TSPOT. LTBI should not be
      ruled out even with a negative IGRA result in patients with CD4 T-cell <650/MUL
      or CD8 T-cell <400/MUL.

PMID- 29054461
TI  - Multiple morbidity in primary care: The public and the private sector.

PMID- 29054462
TI  - Communication with patients and the duration of family medicine consultations.
AB  - OBJECTIVE: To determine the distribution of consultation times, the factors that
      determine their length, and their relationship with a more participative, patient
      centred consulting style. DESIGN: Cross-sectional multicentre study. LOCATION:
      Primary Healthcare Centres in Andalusia, Spain. PARTICIPANTS: A total of 119
      tutors and family medicine physician residents. PRINCIPAL MEASUREMENTS:
      Consultation length and communication with the patient were analysed using the
      CICCAA scale (Connect, Identify, Understand, Consent, Help) during 436 interviews
      in Primary Care. RESULTS: The mean duration of consultations was 8.8min (sd:
      3.6). The consultation tended to be longer when the physician had a patient
      centred approach (10.37+/-4.19min vs 7.54+/-2.98min; p=0.001), and when there was
      joint decision-making (9.79+/-3.96min vs 7.73+/-3.42min: p=0.001). In the
      multivariable model, longer consultations were associated with obtaining higher
      scores on the CICAA scale, a wider range of reasons for consultation, whether
      they came accompanied, in urban centres, and a smaller number of daily visits
      (r2=0.32). There was no correlation between physician or patient gender, or
      problem type. CONCLUSION: A more patient centred medical profile, increased
      shared decision-making, a wider range of reasons for consultation, whether they
      came accompanied, in urban centres, and less professional pressure all seem to be
      associated with a longer consultation.

PMID- 29054463
TI  - Profiling of secondary metabolite gene clusters regulated by LaeA in Aspergillus
      niger FGSC A1279 based on genome sequencing and transcriptome analysis.
AB  - The global regulator LaeA controls the production of many fungal secondary
      metabolites, possibly via chromatin remodeling. Here we aimed to survey the
      secondary metabolite profile regulated by LaeA in Aspergillus niger FGSC A1279 by
      genome sequencing and comparative transcriptomics between the laeA deletion
      (DeltalaeA) and overexpressing (OE-laeA) mutants. Genome sequencing revealed four
      putative polyketide synthase genes specific to FGSC A1279, suggesting that the
      corresponding polyketide compounds might be unique to FGSC A1279. RNA-seq data
      revealed 281 putative secondary metabolite genes upregulated in the OE-laeA
      mutants, including 22 secondary metabolite backbone genes. LC-MS chemical
      profiling illustrated that many secondary metabolites were produced in OE-laeA
      mutants compared to wild type and DeltalaeA mutants, providing potential
      resources for drug discovery. KEGG analysis annotated 16 secondary metabolite
      clusters putatively linked to metabolic pathways. Furthermore, 34 of 61 Zn2Cys6
      transcription factors located in secondary metabolite clusters were
      differentially expressed between DeltalaeA and OE-laeA mutants. Three secondary
      metabolite clusters (cluster 18, 30 and 33) containing Zn2Cys6 transcription
      factors that were upregulated in OE-laeA mutants were putatively linked to KEGG
      pathways, suggesting that Zn2Cys6 transcription factors might play an important
      role in synthesizing secondary metabolites regulated by LaeA. Taken together,
      LaeA dramatically influences the secondary metabolite profile in FGSC A1279.

PMID- 29054464
TI  - Improved kinetic model of Escherichia coli central carbon metabolism in batch and
      continuous cultures.
AB  - Many kinetic models of Escherichia coli central metabolism have been built, but
      few models accurately reproduced the dynamic behaviors of wild type and multiple
      genetic mutants. In 2016, our latest kinetic model improved problems of existing
      models to reproduce the cell growth and glucose uptake of wild type,
      DeltapykA:pykF and Deltapgi in a batch culture, while it overestimated the
      glucose uptake and cell growth rates of Deltappc and hardly captured the typical
      characteristics of the glyoxylate and TCA cycle fluxes for Deltapgi and Deltappc.
      Such discrepancies between the simulated and experimental data suggested
      biological complexity. In this study, we overcame these problems by assuming
      critical mechanisms regarding the OAA-regulated isocitrate dehydrogenase
      activity, aceBAK gene regulation and growth suppression. The present model
      accurately predicts the extracellular and intracellular dynamics of wild type and
      many gene knockout mutants in batch and continuous cultures. It is now the most
      accurate, detailed kinetic model of E. coli central carbon metabolism and will
      contribute to advances in mathematical modeling of cell factories.

PMID- 29054465
TI  - Combating malignant astrocytes: Strategies mitigating tumor invasion.
AB  - Malignant gliomas are glial-derived, primary brain tumors that carry poor
      prognosis. Existing therapeutics are largely ineffective and dramatically affect
      quality of life. The standard of care details a taxing combination of surgical
      resection, radiation of the resection cavity, and temozolomide (TMZ)
      chemotherapy, with treatment extending life by only an average of months (Maher
      et al., 2001; Stupp et al., 2005). Despite scientific and technological
      advancement, surgery remains the most important treatment modality. Therapeutic
      obstacles include xenobiotic protection conveyed by the blood-brain barrier
      (Zhang et al., 2015), invasiveness and therapeutic resistance of tumor cell
      populations (Bao et al., 2006), and distinctive attributes of secondary glioma
      occurrence (Ohgaki and Kleihues, 2013). While these brain malignancies can be
      classified by grade or grouped by molecular subclass, each tumor presents itself
      as its own complication. Based on all of these obstacles, new therapeutic
      approaches are urgently needed. These will likely emerge from numerous exciting
      studies of glioma biology that are ongoing and reviewed here. These show
      unexpected roles for ion channels, amino-acid transporters, and connexin gap
      junctions in supporting the invasive growth of gliomas. These studies have
      identified a number of proteins that may be targeted for therapy in the future.

PMID- 29054466
TI  - Astrocyte reactivity and astrogliosis after spinal cord injury.
AB  - After traumatic injuries of the central nervous system (CNS), including spinal
      cord injury (SCI), astrocytes surrounding the lesion become reactive and
      typically undergo hypertrophy and process extension. These reactive astrocytes
      migrate centripetally to the lesion epicenter and aid in the tissue repair
      process, however, they eventually become scar-forming astrocytes and form a glial
      scar which produces axonal growth inhibitors and prevents axonal regeneration.
      This sequential phenotypic change has long been considered to be unidirectional
      and irreversible; thus glial scarring is one of the main causes of the limited
      regenerative capability of the CNS. We recently demonstrated that the process of
      glial scar formation is regulated by environmental cues, such as fibrotic
      extracellular matrix material. In this review, we discuss the role and mechanism
      underlying glial scar formation after SCI as well as plasticity of astrogliosis,
      which helps to foster axonal regeneration and functional recovery after CNS
      injury.

PMID- 29054467
TI  - The multi-dimensional roles of astrocytes in ALS.
AB  - Despite significant progress in understanding the molecular and genetic aspects
      of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease
      characterized by the progressive loss of motor neurons, the precise and
      comprehensive pathomechanisms remain largely unknown. In addition to motor neuron
      involvement, recent studies using cellular and animal models of ALS indicate that
      there is a complex interplay between motor neurons and neighboring non-neuronal
      cells, such as astrocytes, in non-cell autonomous neurodegeneration. Astrocytes
      are key homeostatic cells that play numerous supportive roles in maintaining the
      brain environment. In neurodegenerative diseases such as ALS, astrocytes change
      their shape and molecular expression patterns and are referred to as reactive or
      activated astrocytes. Reactive astrocytes in ALS lose their beneficial functions
      and gain detrimental roles. In addition, interactions between motor neurons and
      astrocytes are impaired in ALS. In this review, we summarize growing evidence
      that astrocytes are critically involved in the survival and demise of motor
      neurons through several key molecules and cascades in astrocytes in both sporadic
      and inherited ALS. These observations strongly suggest that astrocytes have multi
      dimensional roles in disease and are a viable therapeutic target for ALS.

PMID- 29054468
TI  - Fundamental principles of the olfactory code.
AB  - Sensory coding represents a basic principle of all phyla in nature: species
      attempt to perceive their natural surroundings and to make sense of them.
      Ultimately, sensory coding is the only way to allow a species to make the kinds
      of crucial decisions that lead to a behavioral response. In this manner, animals
      are able to detect numerous parameters, ranging from temperature and humidity to
      light and sound to volatile or non-volatile chemicals. Most of these
      environmental cues represent a clearly defined stimulus array that can be
      described along a single physical parameter, such as wavelength or frequency;
      odorants, in contrast, cannot. The odor space encompasses an enormous and nearly
      infinite number of diverse stimuli that cannot be classified according to their
      positions along a single dimension. Hence, the olfactory system has to encode and
      translate the vast odor array into an accurate neural map in the brain. In this
      review, we will outline the relevant steps of the olfactory code and describe its
      progress along the olfactory pathway, i.e., from the peripheral olfactory organs
      to the first olfactory center in the brain and then to the higher processing
      areas where the odor perception takes place, enabling an organism to make odor
      guided decisions. We will focus mainly on studies from the vinegar fly Drosophila
      melanogaster, but we will also indicate similarities to and differences from the
      olfactory system of other invertebrate species as well as of the vertebrate
      world.

PMID- 29054469
TI  - The acidity of early pregnancy diet and risk of gestational diabetes mellitus.
AB  - BACKGROUNDS & AIMS: Recently, an increasing interest has been addressed to the
      acid-base imbalance in the pathogenesis of diabetes while we are not aware of any
      study among patients affected by gestational diabetes mellitus (GDM). Therefore,
      the purpose of present study was to reveal the potential relation between dietary
      acid load (DAL) and glycemic indices, lipid profiles and GDM odds ratio among
      Iranian pregnant women with GDM. METHODS: This case-control study (hospital-based
      setting) was performed in singleton fetus pregnant women; healthy (n = 263) and
      GDM (n = 200), aged 22-44 years, and between weeks 5-28 of pregnancy. Three-day
      24-h dietary records were applied to determine usual intakes of women. The
      tertiles of protein to potassium ratio (Pr/K) and potential renal acid load
      (PRAL) were calculated and used for statistical analyses. RESULTS: Across
      tertiles of both DAL scores, fasting blood sugar, HbA1C, total cholesterol and
      LDL-C increased significantly. Diastolic blood pressure of participants
      significantly increased only across the tertiles of Pr/K ratio. Participants in
      the highest tertile of Pr/K and PRAL had more than 7 (OR = 7.60; 95% CI: 3.43
      16.84) and 9 times (OR = 9.27; 95% CI: 4.00-21.46) increased odds of gestational
      diabetes mellitus, respectively. CONCLUSION: Women with higher scores of DAL were
      more likely to have gestational diabetes mellitus during pregnancy.

PMID- 29054470
TI  - Circulating adiponectin increases in obese women after sleeve gastrectomy or
      gastric bypass driving beneficial metabolic changes but with no relationship with
      carotid intima-media thickness.
AB  - BACKGROUND & AIMS: Obesity surgery induces beneficial effects in metabolic and
      cardiovascular parameters. Adiponectin increase might be associated with some of
      these changes. However, direct comparison between different surgical techniques
      has not been extensively performed. METHODS: We studied 20 obese women submitted
      to laparoscopic Roux en Y gastric bypass (RYGB) and 20 to sleeve gastrectomy
      (SG). Twenty control women matched for age and baseline metabolic profiles were
      also included. Both patients and controls were followed up for one year after
      surgery or conventional treatment with diet and exercise, respectively. Serum
      adiponectin was measured at baseline, 6 months and 1 year after, as well as lipid
      profiles, sex hormone binding globulin (SHBG), fasting glucose and insulin.
      Carotid intima-media thickness was measured by ultrasonography at baseline and
      after 1 year. RESULTS: Circulating adiponectin increased after obesity surgery
      (more markedly following RYGB than after SG), whereas no changes were observed in
      the controls (Wilks' lambda = 0.659, P < 0.001 for the interaction, P < 0.001 for
      RYGB vs. controls, P = 0.016 for SG vs. controls, P = 0.040 for RYGB vs. SG). The
      percentage increment in adiponectin correlated positively with changes in SHBG (r
      = 0.404, P = 0.002) and negatively with changes in weight (r = -0.531, P <
      0.001), waist circumference (r = -0.426, P = 0.001), fasting glucose (r = -0.356,
      P = 0.006), and insulin (r = -0.496, P < 0.001). No correlation was found with
      carotid intima-media thickness (r = -0.055, P = 0.679). CONCLUSIONS: RYGB induces
      a higher increase in adiponectin than SG, which parallels SHBG, the reduction of
      fasting insulin and insulin resistance. On the other hand, no association was
      found with carotid intima-media, lipid profiles or blood pressure.

PMID- 29054471
TI  - Innate immunity and tolerance toward mitochondria.
AB  - Mitochondria are intracellular organelles that originate from a bacterial
      symbiont, and they retain multiple features of this bacterial ancestry. The
      immune system evolved to detect the presence of invading pathogens, including
      bacteria, to eliminate them by a diversity of antimicrobial mechanisms and to
      mount long-term protective immunity. Due to their bacterial ancestry,
      mitochondria are sensed by the innate immune system, and trigger inflammatory
      responses comparable to those induced by pathogenic bacteria. In both cases,
      innate sensing mechanisms involve Toll-Like Receptors, Formyl Peptide Receptors,
      inflammasomes or the cGAS/STING pathway. Stressed mitochondria release
      mitochondrial molecules, such as cardiolipin and mitochondrial DNA, which are
      sensed as cellular damage potentially caused by infections. Recent research has
      identified several conditions in which mitochondrial stress-induced immunity is
      essential to effective antimicrobial defenses. But, in pathological conditions,
      the abnormal activation of the innate immune system by damaged mitochondria
      results in auto-inflammatory or autoimmune diseases. To prevent undesirable
      mitochondria-targeted responses, immune tolerance toward mitochondria must be
      established, involving regulation of mitophagy and mitochondrial permeability, as
      well as activation of specific nucleases and pro-apoptotic caspases. Overall,
      recent findings identify mitochondria as central in the induction of innate
      immunity, and provide new insights as to how immune responses to these multi
      functional organelles might be exploited therapeutically in various disease
      states.

PMID- 29054472
TI  - The mitochondrial respiratory chain: A metabolic rheostat of innate immune cell
      mediated antibacterial responses.
AB  - Upon microbial infection, cells of the innate immune system undergo profound
      metabolic reprogramming in order to eradicate pathogens, promote inflammation,
      and eventually restore tissue homeostasis. Mitochondria are at the core of these
      adaptations, given their dual role as metabolic hubs and innate immune signaling
      platforms. The mitochondrial electron transport chain (ETC) is very well
      characterized at the genetic, molecular, structural, and biochemical level. In
      contrast, the role for mitochondrial ETC and metabolites beyond fulfilling
      cellular ATP synthesis in innate immune cell biology was not understood until
      recently. Here we discuss the latest advances in our understanding of immune
      functions of mitochondria and particularly the mitochondrial respiratory chain.

PMID- 29054473
TI  - Mitochondrial disorders of the retinal ganglion cells and the optic nerve.
AB  - OBJECTIVES: To summarise and discuss recent findings and future perspectives
      concerning mitochondrial disorders (MIDs) affecting the retinal ganglion cells
      and the optic nerve (mitochondrial optic neuropathy. MON). METHOD: Literature
      review. RESULTS: MON in MIDs is more frequent than usually anticipated. MON may
      occur in specific as well as non-specific MIDs. In specific and non-specific
      MIDs, MON may be a prominent or non-prominent phenotypic feature and due to
      mutations in genes located either in the mitochondrial DNA (mtDNA) or the nuclear
      DNA (nDNA). Clinically, MON manifests with painless, bilateral or unilateral,
      slowly or rapidly progressive visual impairment and visual field defects. In some
      cases, visual impairment may spontaneously recover. The most frequent MIDs with
      MON include LHON due to mutations in mtDNA-located genes and autosomal dominant
      optic atrophy (ADOA) or autosomal recessive optic atrophy (AROA) due to mutations
      in nuclear genes. Instrumental investigations for diagnosing MON include
      fundoscopy, measurement of visual acuity, visual fields, and color vision,
      visually-evoked potentials, optical coherence tomography, fluorescein
      angiography, electroretinography, and MRI of the orbita and cerebrum. In non
      prominent MON, work-up of the muscle biopsy with transmission electron microscopy
      may indicate mitochondrial destruction. Treatment is mostly supportive but
      idebenone has been approved for LHON and experimental approaches are promising.
      CONCLUSIONS: MON needs to be appreciated, requires extensive diagnostic work-up,
      and supportive treatment should be applied although loss of vision, as the most
      severe outcome, can often not be prevented.

PMID- 29054474
TI  - Deubiquitylating enzymes as cancer stem cell therapeutics.
AB  - The focus of basic and applied research on core stem cell transcription factors
      has paved the way to initial delineation of their characteristics, their
      regulatory mechanisms, and the applicability of their regulatory proteins for
      protein-induced pluripotent stem cells (protein-IPSC) generation and in further
      clinical settings. Striking parallels have been observed between cancer stem
      cells (CSCs) and stem cells. For the maintenance of stem cells and CSC
      pluripotency and differentiation, post translational modifications (i.e.,
      ubiquitylation and deubiquitylation) are tightly regulated, as these
      modifications result in a variety of stem cell fates. The identification of
      deubiquitylating enzymes (DUBs) involved in the regulation of core stem cell
      transcription factors and CSC-related proteins might contribute to providing
      novel insights into the implications of DUB regulatory mechanisms for governing
      cellular reprogramming and carcinogenesis. Moreover, we propose the novel
      possibility of applying DUBs coupled with core transcription factors to improve
      protein-iPSC generation efficiency. Additionally, this review article further
      illustrates the potential of applying DUB inhibitors as a novel therapeutic
      intervention for targeting CSCs. Thus, defining DUBs as core pharmacological
      targets implies that future endeavors to develop their inhibitors may
      revolutionize our ability to regulate stem cell maintenance and differentiation,
      somatic cell reprogramming, and cancer stem cells.

PMID- 29054475
TI  - New insights into sorafenib resistance in hepatocellular carcinoma: Responsible
      mechanisms and promising strategies.
AB  - It is disappointing that only a few patients with hepatocellular carcinoma (HCC)
      obtain a significant survival benefit from the sorafenib treatment, which is
      currently regarded as a first-line chemotherapeutic therapy in patients with
      advanced HCC. Most patients are highly refractory to this therapy. Therefore, it
      is necessary to identify resistant factors and explore potential protocols that
      can be used to overcome the resistance or substitute sorafenib once the
      resistance is formed. In fact, a growing body of studies has been focusing on the
      resistance mechanisms or the method to overcome it. The limitation of sorafenib
      efficacy has been partially but not fully elucidated. Moreover, some protocols
      have shown encouraging outcomes but still need to be further verified in clinical
      trials. In this review, we summarize the recent findings on the potential
      mechanisms that contribute to sorafenib resistance and discuss strategies that
      can be used to improve the treatment outcome.

PMID- 29054477
TI  - [Update on recommendations for screening for hydroxychloroquine retinopathy].
AB  - INTRODUCTION: Recommendations for screening for chloroquine (CQ) and
      hydroxychloroquine (HCQ) retinopathy have recently been changed by the American
      Academy of Ophthalmology, taking into account new published data on toxicity
      prevalence, risk factors, location of onset in the retina and the efficacy of
      screening tests. METHODS: Literature review. RESULTS AND DISCUSSION: The risk of
      developing CQ or HCQ retinopathy depends on the daily dose and duration of
      treatment. At recommended doses, the risk is<1 % at 5 years, <2 % at 10years but
      increases to about 20 % after 20years of treatment. The maximum recommended daily
      dose is 5.0mg/kg for HCQ and 2.3mg/kg for CQ. The two main risk factors are the
      daily dose and duration of treatment. The presence of kidney failure and
      treatment with tamoxifen are also significant risk factors. A baseline
      examination should be performed at the initiation of treatment to rule out pre
      existing maculopathy. The screening is then annual and starts from the 5th year
      of treatment. The two tests recommended for screening are the automated visual
      field and spectral domain OCT. Multifocal ERG and autofluorescence fundus imaging
      are only carried out secondarily to confirm the pathology.

PMID- 29054478
TI  - Bilateral retinal detachment associated with cytomegalovirus retinitis.

PMID- 29054479
TI  - [Vitreous hemorrhage during angiography].

PMID- 29054480
TI  - [Whitnall's ligament suspension technique in ptosis surgery].
AB  - INTRODUCTION: We report our experience in ptosis surgery using the technique of
      Whitnall's ligament suspension in congenital ptosis. MATERIALS AND METHODS: A
      retrospective study of 20 cases of congenital ptosis treated by the technique of
      Whitnall's ligament suspension, 8 by the posterior approach and 12 by the
      anterior approach. Patients were randomized into 3 groups according to upper
      eyelid levator function. Postoperative follow-up was obtained on day 1, one week,
      one month, three months and one year. RESULTS: All patients had good correction;
      3 had an under-correction as a three-month final result, of which only one
      required reoperation for an unsatisfactory result. There was no abnormal
      curvature of the lid margin or malposition of the lid crease. All lids required
      initial over-correction, which yielded a good end result. The success rate was
      85%. DISCUSSION: The technique of Whitnall's ligament suspension for the
      treatment of ptosis has rarely been described in the literature, but the few
      studies reported show its equivalence in terms of results to other surgical
      techniques for treatment of ptosis and also confirm its superiority in terms of
      respect for anatomy and physiology of the eyelid. CONCLUSION: This technique is
      particularly suited to the treatment of congenital ptosis with moderate levator
      function, and the results are promising.

PMID- 29054481
TI  - [Impressive extension into the right heart cavities and the inferior vena cava of
      renal carcinoma].
AB  - Renal carcinoma is an aggressive cancer with a high metastatic tendency. It may
      invade the renal vein, inferior vena cava and potentially extend in some cases to
      the right heart cavities. We report a case of a 71-year-old male presenting with
      an impressive polylobular tissular mass inside the right atrium and the right
      ventricle revealing an aggressive renal carcinoma extending through the inferior
      vena cava.

PMID- 29054476
TI  - Extracellular vesicles as emerging targets in cancer: Recent development from
      bench to bedside.
AB  - Extracellular vesicles (EVs) have emerged as important players of cancer
      initiation and progression through cell-cell communication. They have been
      recognized as critical mediators of extracellular communications, which promote
      transformation, growth invasion, and drug-resistance of cancer cells.
      Interestingly, the secretion and uptake of EVs are regulated in a more controlled
      manner than previously anticipated. EVs are classified into three groups, (i)
      exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (ABs), based on
      their sizes and origins, and novel technologies to isolate and distinguish these
      EVs are evolving. The biologically functional molecules harbored in these EVs,
      including nucleic acids, lipids, and proteins, have been shown to induce key
      signaling pathways in both tumor and tumor microenvironment (TME) cells for
      exacerbating tumor development. While tumor cell-derived EVs are capable of
      reprogramming stromal cells to generate a proper tumor cell niche, stromal
      derived EVs profoundly affect the growth, resistance, and stem cell properties of
      tumor cells. This review summarizes and discusses these reciprocal communications
      through EVs in different types of cancers. Further understanding of the
      pathophysiological roles of different EVs in tumor progression is expected to
      lead to the discovery of novel biomarkers in liquid biopsy and development of
      tumor specific therapeutics. This review will also discuss the translational
      aspects of EVs and therapeutic opportunities of utilizing EVs in different cancer
      types.

PMID- 29054482
TI  - The effectiveness of an obstructive sleep apnea screening and treatment program
      in patients with type 2 diabetes.
AB  - AIMS: As recommended by current guidelines, we tested the acceptability and
      impact of screening patients with type 2 diabetes for obstructive sleep apnea
      (OSA). METHODS: In a large urban primary care practice, we instituted a telephone
      based OSA screening program using a validated tool (STOP-BANG) in patients with
      type 2 diabetes. Patients identified as high risk were referred for diagnostic
      sleep testing, and those diagnosed with OSA were offered positive airway pressure
      (PAP) therapy. We evaluated the impact of PAP on sleep-related symptoms, glycemic
      control, and hospitalization rates. RESULTS: We identified 738 of 818 (90.1%)
      patients with type 2 diabetes as high risk for OSA. Only 29.2% (n = 213) of high
      risk patients were willing to undergo diagnostic sleep testing. The prevalence of
      OSA was 90.6% in this group, but only 66.0% of those with OSA initiated PAP.
      Patients with higher burden of sleep symptoms were more likely to pursue testing
      and initiate therapy. PAP use was associated with reduced sleep-related symptoms
      (mean Epworth sleepiness scale score declined from 8.8 to 7.3, p < .001), but did
      not impact hemoglobin A1c levels at one year (7.7-7.9%, p = .12). Changes in
      glycemic control and hospitalization rates did not differ from comparator groups.
      CONCLUSIONS: Despite a high prevalence of OSA, willingness to pursue diagnostic
      testing and treatment was low in an unselected type 2 diabetes population.
      Furthermore, glycemic control did not improve. Future screening programs should
      focus on patients with substantial sleep related symptoms as this group is most
      likely to derive benefit from treatment.

PMID- 29054483
TI  - Risk and associates of incident hip fracture in type 1 diabetes: The Fremantle
      Diabetes Study.
AB  - AIMS: To determine the relative risk of incident hip fracture in patients with
      type 1 diabetes and matched controls, to examine baseline associates of incident
      hip fracture in the patients with type 1 diabetes, and to compare hip fracture
      rates in age- and sex-matched patients with type 1 versus type 2 diabetes.
      METHODS: Longitudinal observational study of 121 adults with type 1 diabetes
      (mean +/- SD age 43.0 +/- 15.5 years, 59.5% male) and 484 age- and sex-matched
      adults without diabetes. Age and sex matching was possible for 93 pairs of type 1
      and type 2 participants. The main outcome measure was incident hip fracture
      hospitalisation. RESULTS: During a mean +/- SD 14.5 +/- 5.8 years of follow-up,
      the incidence rate ratio for first hip fracture hospitalisation in type 1
      participants versus residents without diabetes was 6.39 (95% CI 1.94-22.35, P <
      .001). In Cox proportional hazards modelling, type 1 diabetes was associated with
      cause-specific hazard ratio (csHR) for hip fracture of 7.11 (2.45-20.64, P <
      .001) after age and sex adjustment. Hip fracture in type 1 participants was
      associated with older age, osteoporosis treatment, depressive symptoms,
      ethnicity, systolic blood pressure, serum HDL-cholesterol, albuminuria and serum
      adiponectin (P <= 0.047); associations remained for the first three of these
      variables after adjustment for age and body mass index (P <= 0.025). The csHR for
      incident hip fracture was 5.32 (1.12-25.37, P = .036) for type 1 versus 2
      diabetes. CONCLUSIONS: Hip fracture risk is markedly elevated in type 1 diabetes
      compared with age and sex-matched individuals without diabetes and with type 2
      diabetes from the same population.

PMID- 29054484
TI  - Mental health and well-being among type 1 diabetes caregivers in India: Evidence
      from the IDREAM study.
AB  - AIMS: Although more than half of the world's children with T1D live in developing
      countries, still little is known about how caregiving for children with T1D
      affects the parent/caregivers' health in low- and middle-income country settings.
      METHODS: Caregivers of 178 children with T1D from a specialized diabetes clinic
      in Maharashtra, India were surveyed. Ordered and standard logistic regression
      models adjusted for caregiver, household and child characteristics, were fit to
      estimate the association of caregiving burden (objective caregiving burden and
      subjective caregiving burden (Zarit Burden Inventory - tertiles)) with caregiver
      depression (Patient Health Questionnaire [PHQ-9]) and well-being (CDC Unhealthy
      Days) outcomes. RESULTS: Caregivers with high subjective caregiving burden had a
      41% probability of most severe depression category (probability: 0.41, 95% CI:
      0.25, 0.57) and an 39% probability of low well-being (probability: 0.39, 95% CI:
      0.27, 0.51), compared to caregivers with low subjective burden. Caregivers with
      high subjective caregiving burden and high objective direct caregiving burden had
      an adjusted 30% probability of elevated depressive symptoms (PHQ>=10).
      CONCLUSIONS: Among Indian T1D caregivers, high subjective caregiving burden and
      objective direct caregiving burden were associated with a high risk for caregiver
      depression and poorer well-being.

PMID- 29054485
TI  - Genetic correlates of insight in schizophrenia.
AB  - : Insight in schizophrenia is clinically important as it is associated with
      several adverse outcomes. Genetic contributions to insight are unknown. We
      examined genetic contributions to insight by investigating if polygenic risk
      scores (PRS) and candidate regions were associated with insight. METHOD:
      Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of
      Intervention Effectiveness trial. Schizophrenia PRS was constructed using
      Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set.
      For candidate regions, we selected 105 schizophrenia-associated autosomal loci
      and 11 schizophrenia-related oligodendrocyte genes. We used regressions to
      examine PRS associations and set-based testing for candidate analysis. RESULTS:
      We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was
      associated with total insight (R2=0.005, P=0.05, empirical P=0.054) and treatment
      insight (R2=0.005, P=0.048, empirical P=0.048). For models that controlled for
      neurocognition, PRS significantly predicted treatment insight but at higher p
      thresholds (0.1 to 0.5) but did not survive correction. Patients with highest
      polygenic burden had 5.9 times increased risk for poor insight compared to
      patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of
      variance in poor insight. Set-based analyses identified two variants associated
      with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR
      P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). CONCLUSION:
      To the best of our knowledge, this is the first study examining genetic basis of
      insight. We provide evidence for genetic contributions to impaired insight.
      Relevance of findings and necessity for replication are discussed.

PMID- 29054486
TI  - Prevalence of underweight in patients with schizophrenia: A meta-analysis.
AB  - AIMS: Although the relationship between body mass index and all-cause mortality
      is U-shaped, underweight has received comparatively less attention than obesity.
      There is only limited evidence to date regarding underweight among patients with
      schizophrenia. This is the first meta-analysis to address the prevalence of
      underweight in these patients. METHODS: We conducted database searches (PubMed,
      PsycINFO) to identify studies examining underweight in patients with
      schizophrenia. In total, 17 studies (18 groups) with 45,474 patients were
      included; data were extracted independently by two authors. A meta-analysis was
      performed to calculate the pooled prevalence of underweight in patients. RESULTS:
      The pooled prevalence of underweight was 6.2% (95% CI=4.5-8.6) for the 18 groups,
      which included 45,474 patients with schizophrenia. The heterogeneity was I2=98.9%
      (95% Cl=98.7-99.1%). Four studies with 4 groups, consisting of 30,014
      individuals, focused on Japanese inpatients with schizophrenia. The pooled
      prevalence of underweight among inpatients in these 4 groups was 17.6% (95%
      CI=15.5-20.0). Fourteen studies were conducted with non-Japanese inpatients and
      included 14 groups of 15,460 patients with schizophrenia. The pooled prevalence
      of underweight in non-Japanese inpatients was 4.6% (95% CI=3.9-5.4). The
      proportion of underweight in the 18 groups significantly varied between Japanese
      inpatients and other patients. CONCLUSIONS: The results indicated that Japanese
      inpatients with schizophrenia have a high proportion of underweight. Future
      research should focus on evaluating interventions that target underweight.

PMID- 29054487
TI  - Patterns of self-care and clinical events in a cohort of adults with heart
      failure: 1 year follow-up.
AB  - BACKGROUND: Heart failure (HF) self-care is important in reducing clinical events
      (all-cause mortality, emergency room visits and hospitalizations). HF self-care
      behaviors are multidimensional and include maintenance (i.e. daily adherence
      behaviors), management (i.e. symptom response behaviors) and consulting behaviors
      (i.e. contacting a provider when appropriate). Across these dimensions, patterns
      of successful patient engagement in self-care have been observed (e.g. successful
      in one dimension but not in others), but no previous studies have linked patterns
      of HF self-care to clinical events. OBJECTIVES: To identify patterns of self-care
      behaviors in HF patients and their association with clinical events. METHODS:
      This was a prospective, non-experimental, cohort study. Community-dwelling HF
      patients (n = 459) were enrolled across Italy, and clinical events were collected
      one year after enrollment. We measured dimensions of self-care behavior with the
      Self-Care of HF Index (maintenance, management, and confidence) and the European
      HF Self-care Behavior Scale (consulting behaviors). We used latent class mixture
      modeling to identify patterns of HF self-care across dimensions, and Cox
      proportional hazards modeling to quantify event-free survival over 12 months of
      follow-up. RESULTS: Patients (mean age 71.8 +/- 12.1 years) were mostly males
      (54.9%). Three patterns of self-care behavior were identified; we labeled each by
      their most prominent dimensional characteristic: poor symptom response, good
      symptom response, and maintenance-focused behaviors. Patients with good symptom
      response behaviors had fewer clinical events compared with those who had poor
      symptom response behaviors (adjusted hazard ratio = 0.66 [0.46-0.96], p = 0.03).
      Patients with poor symptom response behaviors had the most frequent clinical
      events. Patients with poor symptom response and those with maintenance-focused
      behaviors had a similar frequency of clinical events. CONCLUSIONS: Self-care is
      significantly associated with clinical events. Routine assessment, mitigation of
      barriers, and interventions targeting self-care are needed to reduce clinical
      events in HF patients.

PMID- 29054488
TI  - The histone demethylase JMJD2A regulates the expression of BDNF and mediates
      neuropathic pain in mice.
AB  - JMJD2A is a JmjC histone demethylase that catalyzes the demethylation of di- and
      trimethylated Lys9 and Lys36 in histone H3 (H3K9me2/3 and H3K36me2/3). The role
      of spinal JMJD2A-dependent histone demethylation in nociception hypersensitivity
      development remains elusive. Here we reported that the JMJD2A responded to
      neuropathic pain and participated in the maintenance of neuropathic pain. The
      mRNA and protein levels of Jmjd2a were significantly increased in the neurons of
      mouse undergoing neuropathic pain induced by sciatic nerve chronic constrictive
      injury (CCI) or unilateral spared nerve injury (SNI). Jmjd2a responded to 5
      hydroxytryptamine (5-HT) and promoted the expression of the brain-derived
      neurotrophic factor (Bdnf), which is a protein critically involved in neuropathic
      pain. JMJD2A bound to the promoter of Bdnf and demethylated H3K9me3 and H3K36me3
      at Bdnf promoter to promote the expression of Bdnf. Finally, we showed that
      JMJD2A promoted the expression of Bdnf during neuropathic pain and neuron
      specific knockout of Jmjd2a blocked the hypersensitivity of mice undergoing
      chronic neuropathic pain induced by CCI and SNI. Taken together, our findings
      demonstrate that up-regulation of JMJD2A promotes neuropathic pain and it may
      serve as a promising target for treatment of chronic neuropathic pain.

PMID- 29054489
TI  - Msi2 plays a carcinogenic role in esophageal squamous cell carcinoma via
      regulation of the Wnt/beta-catenin and Hedgehog signaling pathways.
AB  - Msi2 has been widely reported to be upregulated and strongly associated with fast
      progress and poor prognosis in many cancers. However, the expression and role of
      Msi2 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study,
      we found that Msi2 was upregulated in ESCC clinical samples, and was
      significantly associated with tumor size, differentiation status, and lymph node
      metastasis in ESCC patients. Multivariate Cox regression analysis showed that
      Msi2 was an independent predictor for disease-free survival (DFS) and overall
      survival (OS). Moreover, knockdown of Msi2 impaired ESCC cell proliferation,
      epithelial-mesenchymal transition (EMT) and migration, while overexpression of
      Msi2 promoted ESCC cell proliferation, EMT and migration in vitro. Animal
      experiments also confirmed that Msi2 promoted ESCC cell proliferation in vivo.
      Mechanistically, Msi2 promoted ESCC cell proliferation, EMT and migration via
      regulation of the Wnt/beta-catenin and Hedgehog (Hh) signaling pathways. Taken
      together, our study suggested that Msi2 could serve as a candidate for diagnosis
      and prognosis and as a potential therapeutic target in ESCC.

PMID- 29054490
TI  - CD21lo/medCD27+ proinflammatory B cells are enriched in breast cancer patients
      and promote antitumor T cell responses.
AB  - Breast cancer is a common malignancy and a major cause of death in women
      worldwide. The immunomodulatory role of B cells is being increasingly recognized
      in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies
      that upregulate the patient's own antitumor T cell responses have shown promise
      in treating solid tumors and are being developed for breast cancer. In this
      study, we discovered that the B cells in breast cancer patients were enriched
      with interferon (IFN)-gamma-expressing cells and presented high potency for IFN
      gamma production. These IFN-gamma-expressing B cells were enriched in, but did
      not completely overlap with, the CD21lo/medCD27+IgM-IgD-IgG+IgA- B cell subset,
      which was consistent with IgG-expressing memory B cells. Compared to CD27+IgG- B
      cells, the CD27+IgG+ B cells expressed significantly higher IFN-gamma expression.
      Given that B cells demonstrate important antigen-presenting function to T cells,
      we incubated CD27+IgG- B cells and CD27+IgG+ B cells with autologous CD4+ T
      cells. Compared to the CD4+ T cells that were incubated with CD27+IgG- B cells,
      the CD4+ T cells that were incubated with CD27+IgG+ B cells presented
      significantly higher TBX21 and lower FOXP3 expression, suggesting that the
      CD27+IgG+ B cells, but not the CD27+IgG- B cells, promoted Th1 and suppressed
      regulatory T cell responses. IFN-gamma-expressing B cells were further enriched
      in the intratumoral environment of breast cancer patients. Together, we
      discovered that breast cancer patients presented an upregulation of IFN-gamma
      expressing proinflammatory B cells with the potency to promote Th1 responses.

PMID- 29054491
TI  - Cardiovascular risk factors in children.
AB  - INTRODUCTION: Systemic hypertension is one of the main risk factors for
      cardiovascular disease (CVD). Early diagnosis and treatment of hypertension in
      childhood can potentially have a significant impact on future adverse outcomes.
      OBJECTIVE: To investigate the relationship of diastolic (DBP) and systolic blood
      pressure (SBP) with anthropometric data and area of residence of children in
      municipalities of Rio Grande do Sul state, Brazil. METHODS: This is a cross
      sectional study of 709 children between six and nine years of age. Blood
      pressure, weight, height and waist circumference (WC) were measured. Statistical
      tests had a maximum significance level of 5% (p<=0.05) and the software used was
      SPSS version 13.0. RESULTS: Obesity was significantly associated with pre
      hypertension, and stage 1 and 2 hypertension as assessed by DBP and SBP (<=0.05);
      high WC was significantly associated with a classification of pre-hypertension
      and stage 1 hypertension based on DBP and a classification of stage 1 and 2
      hypertension based on SBP (<=0.01). CONCLUSION: Children living in urban areas
      had significantly higher mean SBP than those living in rural areas. Those with
      high WC presented higher SBP and DBP compared to children with normal WC. Obese
      children showed higher mean SBP and DBP compared to those who were overweight or
      normal weight and mean SBP and DBP also increased with older age and higher mean
      body mass index and WC.

PMID- 29054492
TI  - A Cost-Analysis of an Interdisciplinary Pediatric Chronic Pain Clinic.
AB  - : Chronic pain is characterized by high rates of functional impairment, health
      care utilization, and associated costs. Research supports the use of
      comprehensive, interdisciplinary treatment approaches. However, many hospitals
      hesitate to offer this full range of services, especially to Medi-Cal/Medicaid
      patients whose services are reimbursed at low rates. This cost analysis examines
      the effect on hospital and insurance costs of patients' enrollment in an
      interdisciplinary pediatric pain clinic, which includes medication management,
      psychotherapy, biofeedback, acupuncture, and massage. Retrospective hospital
      billing data (inpatient/emergency department/outpatient visits, and associated
      costs/reimbursement) from 191 consecutively enrolled Medi-Cal/Medicaid pediatric
      patients with chronic pain were used to compare 1-year costs before initiating
      pain clinic services with costs 1 year after. Pain clinic patients had
      significantly fewer emergency department visits, fewer inpatient stays, and lower
      associated billing, compared with the year before without interdisciplinary pain
      management services. Cost savings to the hospital of $36,228 per patient per year
      and to insurance of $11,482 per patient per year were found even after pain
      clinic service billing was included. Analyses of pre-pain clinic costs indicate
      that these cost reductions were likely because of clinic participation. Findings
      provide economic support for the use of interdisciplinary care to treat pediatric
      chronic pain on an outpatient basis from a hospital and insurance perspective.
      PERSPECTIVE: This article presents a cost analysis of an interdisciplinary
      pediatric pain outpatient clinic. Findings support the incorporation of a
      comprehensive treatment approach that can reduce costs from a hospital and
      insurance perspective over the course of just 1 year.

PMID- 29054494
TI  - Corrigendum to "The digestive morphophysiology of wild, free-living, giraffes"
      [Comp. Biochem. Physiol., A 187 (2015) 119-129].

PMID- 29054493
TI  - Association of Prescription Drug Monitoring Program Use With Opioid Prescribing
      and Health Outcomes: A Comparison of Program Users and Nonusers.
AB  - : Prescription drug monitoring programs (PDMPs) are a response to the
      prescription opioid epidemic, but their effects on prescribing and health
      outcomes remain unclear, with conflicting reports. We sought to determine if
      prescriber use of Oregon's PDMP led to fewer high-risk opioid prescriptions or
      overdose events. We conducted a retrospective cohort study from October 2011
      through October 2014, using statewide PDMP data, hospitalization registry, and
      vital records. Early PDMP registrants (n = 927) were matched with clinicians who
      never registered during the study period, using baseline prescribing metrics in a
      propensity score. Generalized estimating equations were used to examine
      prescribing trends after PDMP registration, using 2-month intervals. We found a
      statewide decline in measures of per capita opioid prescribing. However, compared
      with nonregistrants, PDMP registrants did not subsequently have significantly
      fewer patients receiving high-dose prescriptions, overlapping opioid and
      benzodiazepine prescriptions, inappropriate prescriptions, prescriptions from
      multiple prescribers, or overdose events. At baseline, frequent PDMP users wrote
      fewer high-risk opioid prescriptions than infrequent users; this persisted during
      follow-up with few significant group differences in trend. Thus, although opioid
      prescribing declined statewide after implementing the PDMP, registrants did not
      show greater declines than nonregistrants. PERSPECTIVE: Factors other than PDMP
      use may have had greater influence on prescribing trends. Refinements in the PDMP
      program and related policies may be necessary to increase PDMP effects.

PMID- 29054495
TI  - Renal mass biopsy for the small renal mass.
AB  - Opponents of premanagement biopsy of small renal masses are not difficult to
      find. Many urologists contend that the benefits of biopsy do not outweigh the
      risks, arguing that the results do not influence management substantially and
      that the most useful information from renal mass biopsy can be attained with
      advanced imaging. In this article, we develop the counter arguments and
      demonstrate that renal mass biopsy should be implemented into the small renal
      mass management algorithm.

PMID- 29054496
TI  - Cancer immunotherapy: A paradigm shift in the treatment of advanced urologic
      cancers.
AB  - The recent resurgence of immunotherapy has transformed the therapeutic field of
      advanced urologic cancers. In this seminars issue, we evaluate the role of
      emerging and recently approved immunotherapeutic agents in advanced prostate,
      urothelial, and renal cell carcinoma. In each of these fields, we discuss recent
      regulatory approvals as well as promising ongoing clinical trials. Finally, we
      discuss incidence and management of immune related adverse events specifically
      associated with PD-1/PD-L1 inhibitors.

PMID- 29054497
TI  - Association between male pattern baldness and prostate disease: A meta-analysis.
AB  - BACKGROUND: Male pattern baldness (MPB) has been associated with an increased
      risk of prostate cancer (PC) as well as benign prostatic hyperplasia (BPH). We
      performed a meta-analysis to quantitatively determine the level of risk of PC and
      BPH in individuals with baldness. METHODS: A systematic literature search was
      conducted using several databases. We calculated pooled odds ratios (OR) and 95%
      CIs. RESULTS: In total, 17 studies comprising 68,448 participants were eligible
      for the meta-analysis and showed that MPB is associated with an increased risk of
      aggressive PC (OR = 1.59; 95% CI: 1.36-1.86; P<0.001) as well as BPH (OR = 1.26;
      95% CI: 1.05-1.51; P = 0.01). There was statistically significant association
      between vertex baldness and PC (OR = 1.18; 95% CI: 1.05-1.32; P = 0.006). No
      statistically significant association between vertex, frontal plus vertex hair
      loss pattern, and BPH were identified. CONCLUSIONS: MPB is associated with an
      increased risk of PC and BPH. Despite our findings, further studies, preferably
      prospective cohort studies, are required to better elucidate these relationships
      and to advance knowledge in this field.

PMID- 29054498
TI  - Erratum to "Psychogenic nonepileptic seizures: Namibian healthcare providers'
      perceptions and frustrations'' [Seizure 50 (2017) 43-52].

PMID- 29054499
TI  - Coupled in silico platform: Computational fluid dynamics (CFD) and
      physiologically-based pharmacokinetic (PBPK) modelling.
AB  - One of the critical components of the respiratory drug delivery is the manner in
      which the inhaled aerosol is deposited in respiratory tract compartments.
      Depending on formulation properties, device characteristics and breathing
      pattern, only a certain fraction of the dose will reach the target site in the
      lungs, while the rest of the drug will deposit in the inhalation device or in the
      mouth-throat region. The aim of this study was to link the Computational fluid
      dynamics (CFD) with physiologically-based pharmacokinetic (PBPK) modelling in
      order to predict aerolisolization of different dry powder formulations, and
      estimate concomitant in vivo deposition and absorption of amiloride
      hydrochloride. Drug physicochemical properties were experimentally determined and
      used as inputs for the CFD simulations of particle flow in the generated 3D
      geometric model of Aerolizer(r) dry powder inhaler (DPI). CFD simulations were
      used to simulate air flow through Aerolizer(r) inhaler and Discrete Phase Method
      (DPM) was used to simulate aerosol particles deposition within the fluid domain.
      The simulated values for the percent emitted dose were comparable to the values
      obtained using Andersen cascade impactor (ACI). However, CFD predictions
      indicated that aerosolized DPI have smaller particle size and narrower size
      distribution than assumed based on ACI measurements. Comparison with the
      literature in vivo data revealed that the constructed drug-specific PBPK model
      was able to capture amiloride absorption pattern following oral and inhalation
      administration. The PBPK simulation results, based on the CFD generated particle
      distribution data as input, illustrated the influence of formulation properties
      on the expected drug plasma concentration profiles. The model also predicted the
      influence of potential changes in physiological parameters on the extent of
      inhaled amiloride absorption. Overall, this study demonstrated the potential of
      the combined CFD-PBPK approach to model inhaled drug bioperformance, and
      suggested that CFD generated results might serve as input for the prediction of
      drug deposition pattern in vivo.

PMID- 29054500
TI  - Re: Impact of Radical Prostatectomy on Long-term Oncologic Outcomes in a Matched
      Cohort of Men with Pathological Node Positive Prostate Cancer Managed by
      Castration.

PMID- 29054501
TI  - Transcriptomic discovery and comparative analysis of neuropeptide precursors in
      sea cucumbers (Holothuroidea).
AB  - Neuropeptides synthesized and released by neuronal cells play important roles in
      the regulation of many processes, e.g. growth, feeding, reproduction, and
      behavior. In the past decade, next-generation sequencing technologies have helped
      to facilitate the identification of multiple neuropeptide genes in a variety of
      taxa, including arthropods, molluscs and echinoderms. In this study, we extend
      these studies to Holothuria scabra, a sea cucumber species that is widely
      cultured for human consumption. In silico analysis of H. scabra neural and
      gonadal transcriptomes enabled the identification of 28 transcripts that encode a
      total of 26 bilaterian and echinoderm-specific neuropeptide precursors.
      Furthermore, publicly available sequence data from another sea cucumber,
      Holothuria glaberrima, allowed a more in-depth comparative investigation.
      Interestingly, two isoforms of a calcitonin-type peptide precursor (CTPP) were
      deduced from the H. scabra transcriptome - HscCTPP-long and HscCTPP-short, likely
      the result of alternative splicing. We also identified a sea cucumber relaxin
      type peptide precursor, which is of interest because relaxin-type peptides have
      been shown to act as gonadotropic hormones in starfish. Two neuropeptides that
      appear to be holothurian-specific are GLRFA, and GN-19. In H. scabra, the
      expression of GLRFA was restricted to neural tissues, while GN-19 expression was
      additionally found in the longitudinal muscle and intestinal tissues. In
      conclusion, we have obtained new insights into the neuropeptide signaling systems
      of holothurians, which will facilitate physiological studies that may enable
      advances in the aquaculture of sea cucumbers.

PMID- 29054502
TI  - Epidemiology and Risk Factors of Uterine Fibroids.
AB  - Risk factors, both modifiable and non-modifiable, are associated with the
      development of fibroids. These include age, race, endogenous and exogenous
      hormonal factors, obesity, uterine infection, and lifestyle (diet, caffeine and
      alcohol consumption, physical activity, stress, and smoking). Some of the
      epidemiological data were conflicting; consequently, further studies are needed
      to better understand the factors that influence fibroid prevalence.

PMID- 29054503
TI  - Theoretical studies on thermal degradation reaction mechanism of model compound
      of bisphenol A polycarbonate.
AB  - Density functional theory methods (DFT) M062X have been used to investigate the
      thermal degradation processes of model compound of bisphenol A polycarbonate
      (MPC) and to identify the optimal reaction paths in the thermal decomposition of
      bisphenol A polycarbonate (PC). The bond dissociation energies of main bonds in
      MPC were calculated, and it is found that the weakest bond in MPC is the single
      bond between the methylic carbon and carbon atom and the second weakest bond in
      MPC is the single bond between oxygen atom and the carbonyl carbon. On the basis
      of computational results of kinetic parameters, a mechanism is proposed where the
      hydrolysis (or alcoholysis) reaction is the main degradation pathways for the
      formation of the evolved products, and the homolytic cleavage and rearrangement
      reactions are the competitive reaction pathways in the thermal degradation of PC.
      The proposed mechanism is consistent with experimental observations of CO2,
      bisphenol A and 1,1-bis(4-hydroxyphenyl)-ethane as the main degradation products,
      together with a small amount of CO, alkyl phenol and diphenyl carbonate.

PMID- 29054504
TI  - Proteomics in plasma of ovariectomized rats and those exposed to estradiol
      valerate.
AB  - The menopausal period, an inevitable physiological process for women, is
      frequently associated with physiological and psychological dysfunction
      attributable to substantial fluctuation and gradual decrease in female hormones
      induced by ovarian failure, leading to corresponding symptoms and diseases that
      impact multiple systems in the body to varying degrees. As prior studies have
      focused primarily on menopausal syndrome-related pathophysiological changes and
      hormone replacement therapy effects, here we approached menopausal disease
      incidence risk and pathogenesis through systemic plasma proteomics analysis.
      Female Sprague-Dawley rats were randomly divided into sham, ovariectomized, and
      estrogen treatment after ovariectomy groups (n=9 per group). Tandem Mass Tag
      quantitative proteomics analysis of their plasma identified over 900 proteins by
      MS. Between group fold change of >1.2 and p<0.05 (Student's t-test) identified
      121 (including 36 up-regulated and 85 down-regulated), 117 (69 up-regulated and
      48 down-regulated), and 109 (41 up-regulated and 68 down-regulated)
      differentially expressed proteins between groups, respectively. Of these, 5 (GHR,
      LIFR, apoA IV, RTN, and Lin28b) were verified by parallel reaction monitoring to
      be reliable. Further application of optimized screening criteria and performance
      of a series of bioinformatics analyses allowed the selection of 35 optimal
      differentially expressed proteins. Gene ontology annotation results suggested
      that the differentially expressed proteins are mainly annotated as protein
      binding, cell, and single organism process in terms of molecular function, cell
      composition, and biological process, respectively. KEGG pathway analysis
      indicated that the PI3-Akt pathway has the highest aggregation degree of
      differentially expressed proteins. Protein-protein interaction analysis noted
      GLUT4 as an important node protein. This research is the first to comprehensively
      analyze plasma protein changes, together with estrogen efficacy, in
      ovariectomized rats. The findings facilitate our understanding of the molecular
      mechanism of systemic menopausal changes and provide valuable clues for
      developing diagnostic biomarkers for menopausal dysfunctions and selecting
      clinical therapeutic strategies.

PMID- 29054505
TI  - BioMonitor 2 Pilot Study: Early Experience With Implantation of the Biotronik
      BioMonitor 2 Implantable Cardiac Monitor.
AB  - BACKGROUND: The BioMonitor 2 Pilot Study assessed the implantation procedure, the
      sensing amplitude and the remote monitoring transmission success rate of the
      second generation implantable cardiac monitor, the BioMonitor 2 (Biotronik,
      Berlin, Germany). METHODS: This was a prospective, multi-centre, single-arm, non
      randomised study involving seven operators in five sites across Australia. Data
      were collected at implantation, during clinic visits at 1 week and 1 month post
      implantation, and through wireless remote monitoring. RESULTS: Thirty patients
      with indications for long-term cardiac monitoring underwent successful insertion
      of a study device. The median implantation time was 9 minutes (interquartile
      range (IQR) 5-14 mins). The mean R-wave amplitude at 1 week was 0.75+/-0.39mV and
      remained stable over the follow-up period. Within 1 day, 97% of the patients
      connected to the remote monitoring network and daily messages were transmitted on
      93.8% of all study days. Seventy-six per cent of patients transmitted at least
      one subcutaneous ECG (sECG), with a median number of sECGs per patient of seven
      (IQR 3-37) within 28 days. CONCLUSIONS: The results of the BioMonitor 2 Pilot
      study confirm the excellent sensing amplitudes afforded by this new device and
      the utility of the implantation tools and technique. Patient compliance with and
      the transmission success rate of the home monitoring system were excellent.

PMID- 29054506
TI  - SMAD Axis Functions as a Key Mediator for Cardiac Fibrosis.

PMID- 29054507
TI  - Comparison of a Web-Based Teaching Tool and Traditional Didactic Learning for In
      Vitro Fertilization Patients: A Preliminary Randomized Controlled Trial.
AB  - OBJECTIVE: The objective of this prospective RCT was to compare the efficacy of a
      web-based teaching tool to traditional didactic teaching in IVF patients.
      METHODS: Forty women undergoing their first IVF cycle were randomly allocated to
      an interactive web-based teaching session or a nurse-led didactic teaching
      session. The primary outcome measure was participant knowledge regarding the IVF
      process, risks, and logistics assessed before and after the respective teaching
      session. Secondary outcomes included patient stress, assessed before and after
      the respective teaching session, and patient satisfaction, assessed following the
      respective teaching session and on the day of embryo transfer (following
      implementation of the teaching protocol). RESULTS: Both groups demonstrated
      similar and significant improvements in knowledge and stress after exposure to
      their respective teaching sessions. The web-based group was significantly more
      satisfied than the didactic teaching group. Web-based teaching was also shown to
      be equally effective for participants of high versus low income and education
      status for knowledge, stress, and satisfaction. CONCLUSION: This study provides
      preliminary support for the use of web-based teaching as an equally effective
      tool for increasing knowledge and reducing stress compared to traditional
      didactic teaching in IVF patients, with the added benefit of increased patient
      satisfaction.

PMID- 29054508
TI  - Unknown Antenatal HIV-Infection Status Has Declined Over Time in British
      Columbia, Canada.
AB  - OBJECTIVES: The objective was to determine whether the proportion of pregnant
      women with unknown antenatal HIV-infection status is declining over time in
      British Columbia (BC) and whether associated factors are amenable to
      intervention. METHODS: Through a retrospective cohort study of all deliveries in
      the British Columbia Perinatal Data Registry from 2005 to 2011, we examined the
      association between year of delivery and no recorded antenatal HIV test result.
      The trend in unknown antenatal HIV-infection status over time was evaluated by
      the Cochran-Mantel-Haenzsel test and multivariable logistic regression was used
      to determine the odds of unknown antenatal HIV-infection status by year of
      delivery. RESULTS: A total of 299 771 deliveries were included; 9.1% had unknown
      antenatal HIV-infection status with a declining trend from 12.7% to 5.5% from
      2005 to 2011 (P <0.0001). Adjusted for maternal age, parity, gestation, and
      number of antenatal visits, pregnant women were 64% less likely to not have
      antenatal HIV testing in 2011 compared to 2005 (adjusted odds ratio [aOR] 0.36;
      95% CI 0.34-0.38). The odds of no antenatal HIV testing were 54% higher in
      multiparous compared to primiparous women (aOR 1.54; 95% CI 1.49-1.58), and each
      additional antenatal visit reduced the odds of no antenatal HIV testing by 8%
      (aOR 0.92; 95% CI 0.92-0.93). CONCLUSION: The declining trend in unknown
      antenatal HIV-infection status in BC is encouraging. Consistent with Canadian and
      BC HIV testing guidelines, further strengthening of routine testing at the first
      antenatal visit in all pregnancies irrespective of previous HIV testing,
      particularly in multiparous women, could achieve universal pregnancy HIV testing
      in BC.

PMID- 29054509
TI  - The Cost-Effectiveness of Salpingectomies for Family Planning in the Prevention
      of Ovarian Cancer.
AB  - OBJECTIVE: Ovarian cancer is the most lethal gynaecologic cancer. Disease
      prevention may be the only method to reduce the incidence of ovarian cancer. The
      Society of Gynecologic Oncology advised that salpingectomies may be an
      appropriate and feasible strategy for ovarian cancer risk reduction. This study
      conducted an economic evaluation from a societal perspective of bilateral
      salpingectomies versus conventional sterilization techniques in the prevention of
      ovarian cancer. STUDY DESIGN: We performed a micro-cost analysis comparing
      laparoscopic tubal coagulation, tubal clips and bilateral salpingectomies at the
      Michael Garron Hospital, formerly the Toronto East General Hospital, from 2015 to
      2016. A Markov model was used in the cost-effectiveness and cost-utility analyses
      on these surgical procedures in ovarian cancer prevention. Costs were derived for
      the number ovarian cancer cases observed per sterilization method, cancer
      treatment, and associated procedural costs over each cancer patient's lifetime.
      The number of bilateral salpingectomies required to prevent an additional ovarian
      cancer case with the recommended treatment was also estimated. RESULTS: Bilateral
      salpingectomies performed at the Michael Garron Hospital generated savings of
      $7823 per life-year gained (95% CI $3248-$10 190; incremental cost [DeltaC] 
      $907, incremental effect [DeltaE] 0.11 life-years gained) compared with tubal
      clips and savings of $6315 per life-year gained (95% CI -$6360 to $9342; DeltaC 
      $755, DeltaE 0.11 life-years gained) compared with tubal coagulation. Most
      importantly, for every 150 bilateral salpingectomies performed, one case of
      ovarian cancer may be prevented. CONCLUSION: Laparoscopic bilateral salpingectomy
      is the dominant, cost-effective surgical strategy when compared to tubal clips
      and tubal coagulation to prevent ovarian cancer. Laparoscopic bilateral
      salpingectomies reduce costs and enhance quality-adjusted life-years relative to
      the two alternative treatments.

PMID- 29054510
TI  - Safety and Efficiency in a Canadian Outpatient Gynaecological Surgical Centre.
AB  - OBJECTIVE: This study sought to describe safety and efficiency outcomes for
      patients undergoing procedures at the Women's Health Centre, an outpatient
      gynaecological surgical centre in Saskatoon, SK. METHODS: A retrospective chart
      review of surgical outpatient health records was conducted for the period of July
      2014 to June 2015. Data were abstracted using a standardized data form for
      patient admissions during the study period. Primary outcomes of interest included
      procedure time, lead time (registration to discharge), complication rates,
      readmission rates, and reoperation rates. Descriptive statistics were calculated
      using Microsoft Excel and were summarized using frequencies and percentages. The
      Kruskal-Wallis test was performed for lead time and procedural time by using IBM
      SPSS Statistics 24 software (IBM, Armonk, NY). RESULTS: During the study period,
      1720 patients were seen by 21 providers. The mean number of patients seen per
      month was 144. The main services provided include hysteroscopic sterilization,
      non-resectoscopic endometrial ablation, loop electrosurgical excision procedure,
      hysteroscopy, and therapeutic abortion. Pain management was administered by local
      anaesthetic and/or conscious sedation. The mean procedure time was 10 +/- 6
      minutes, whereas the lead time was 171 +/- 43 minutes. Immediate complications
      occurred in 3.9% of patients, the most common being vaginal bleeding (1.3%). The
      long-term complication rate was 5.1%, with the most common complication being
      reoperation in the main operating room, at 2.9%. CONCLUSION: Currently, many
      gynaecological procedures in Canada occur in a formal operating theatre setting.
      Our study demonstrates the safety and efficiency of an alternate setting where
      gynaecological procedures are performed on an outpatient basis by using local
      anaesthetic and conscious sedation.

PMID- 29054511
TI  - MicroRNA-128 expression not associated with glioma-associated epilepsy in WHO
      grades 2 glioma: Data from the Cancer Genome Atlas (TCGA) project.

PMID- 29054512
TI  - Letter Re "Status epilepticus-related etiology, incidence and mortality: A meta
      analysis" by Lv R-J et al., 2017.

PMID- 29054514
TI  - Is neurostimulation through the vagal nerve safe during pregnancy?

PMID- 29054513
TI  - Maternal and fetal outcomes associated with vagus nerve stimulation during
      pregnancy.
AB  - OBJECTIVE: To access the effect of vagus nerve stimulation (VNS) on the outcome
      of pregnancy. METHODS: We used the International Registry of Antiepileptic Drugs
      and Pregnancy (EURAP) and its network to search for women receiving adjunctive
      VNS during pregnancy. Data on maternal and fetal outcomes were extracted from the
      registry databases and outcomes were evaluated. RESULTS: Twenty-six pregnancies
      were identified in 25 women. All women were exposed to a relative high VNS
      stimulation level (mean duty cycle 18%, range 5%-51%). Most women had seizures
      during pregnancy and almost 70% were on antiepileptic drug (AED) polytherapy. The
      proportion of women with obstetrical interventions was 53.9% (95% confidence
      interval [CI] 33.4%-73.4%) which was higher compared to the EURAP average (48.2%;
      95% CI 47.2%-49.1%). One infant (3.9%; 95% CI 0.1%-19.6%) was born with a major
      malformation (unilateral congenital glaucoma), which is within the range expected
      among offspring of AED-treated women. CONCLUSION: Although the present series of
      VNS-exposed pregnancies is the largest reported to date, the sample size is
      insufficient to draw any firm conclusions on the safety of VNS in pregnancy but
      the findings suggest an increased rate of obstetrical interventions, and no clear
      signal of VNS-related teratogenicity.

PMID- 29054515
TI  - Blood Transfusion Management and Transfusion-Related Outcomes in Daratumumab
      Treated Patients With Relapsed or Refractory Multiple Myeloma.
AB  - INTRODUCTION: Daratumumab, a human CD38 monoclonal antibody approved for multiple
      myeloma (MM) treatment, binds red blood cells (RBCs), resulting in
      panagglutination in compatibility tests. Published mitigation methods avoid
      additional testing, ensuring timely release of blood products. Blood transfusion
      management and transfusion-related outcomes of daratumumab-treated patients in
      the SIRIUS study are reported, with emphasis on 2 clinical sites. PATIENTS AND
      METHODS: Patients had MM treated with >= 3 prior lines of therapy, including a
      proteasome inhibitor and an immunomodulatory drug, or were refractory to a
      proteasome inhibitor and an immunomodulatory drug. RBC typing and alloantibody
      screening were performed in gel cards. Antibody identification using RBC panels
      was performed on patients with positive antibody screens. Hematology panels and
      serum chemistry were analyzed <= 2 days before each daratumumab infusion and the
      first daratumumab dose within each treatment cycle, respectively. Pre- and
      posttransfusion hemoglobin values were analyzed retrospectively. RESULTS: At
      clinical cutoff, patients received 236 transfusions; 47 (37.9%) of 124 patients
      received 147 packed RBC transfusions, and 17 (13.7%) received 89 platelet
      transfusions. No hemolysis was reported, and 1 platelet transfusion reaction was
      observed. At Mount Sinai, no transfusion adverse events were observed, no new
      unexpected RBC alloantibodies were identified, and transfusions increased
      hemoglobin values (median, 1.2 g/dL). At Levine Cancer Institute, 6 of 7 patients
      responded to transfusions, with a median hemoglobin change of 1.7 g/dL.
      CONCLUSION: In SIRIUS, no RBC transfusion reactions, including hemolysis, were
      observed. Observations from Mount Sinai and Levine Cancer Institute confirm that
      transfusions may be administered safely to daratumumab-treated patients.

PMID- 29054516
TI  - Eye lens dosimetry and the study on radiation cataract in interventional
      cardiologists.
AB  - PURPOSE: To determine the eye lens dose of the Interventional Cardiology (IC)
      personnel using optically stimulated luminescent dosimeter (OSLD) and the
      prevalence and risk of radiation - associated lens opacities in Thailand. METHODS
      AND RESULTS: 48 IC staff, with age- and sex- matches 37 unexposed controls
      obtained eye examines. Posterior lens change was graded using a modified Merriam
      Focht technique by two independent ophthalmologists. Occupational exposure (mSv)
      was measured in 42 IC staff, using 2 OSLD badges place at inside lead apron and
      at collar. Annual eye lens doses (mSv) were also measured using 4 nanoDots OSL
      placed outside and inside lead glass eyewear. The prevalence of radiation
      associated posterior lens opacities was 28.6% (2/7) for IC, 19.5% (8/41) for
      nurses, and 2.7% (1/37) for controls. The average and range of annual whole body
      effective dose, Hp(10), equivalent dose at skin of the neck, Hp(0.07) and
      equivalent dose at eye lens, Hp(3) were 0.80 (0.05-6.79), 5.88 (0.14-35.28), and
      5.73 (0.14-33.20) mSv respectively. The annual average and range of eye lens dose
      using nano Dots OSL showed the outside lead glass eyewear on left and right sides
      as 8.06 (0.17-32.45), 3.55(0.06-8.04) mSv and inside left and right sides as
      3.91(0.05-14.26) and 2.44(0.06-6.24) mSv respectively. CONCLUSION: Eye lens doses
      measured by OSLD badges and nano Dot dosimeter as Hp(10), Hp(0.07) and Hp(3). The
      eyes of the IC personnel were examined annually by two ophthalmologists for the
      prevalence of cataract induced by radiation.

PMID- 29054517
TI  - Size distribution of salbutamol/ipratropium aerosols produced by different
      nebulizers in the absence and presence of heat and humidification.
AB  - BACKGROUND: Few studies have evaluated the size distribution of inhaled and
      exhaled aerosolized drugs, or the effect of heated humidification on particle
      size and lung deposition. The present study evaluated these aspects of
      bronchodilator (salbutamol/ipratropium) delivery using a lung model in the
      absence and presence of heat and humidification. METHODS: We positioned filters
      to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle
      size distribution was evaluated using an 8-stage Marple personal cascade impactor
      with 0.2-MUm polycarbonate filters. RESULTS: A greater inhaled drug mass was
      delivered using a vibrating mesh nebulizer (VMN) than by using a small volume
      nebulizer (SVN), when heated humidifiers were not employed. When heated and
      humidified medical gas was used, there was no significant difference between the
      inhaled drug mass delivered by the VMN and that delivered by the SVN. A
      significantly greater mass of inhaled 1.55-MUm drug particles was produced by the
      VMN than with the SVN, under heated and humidified conditions. However, the mass
      median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN
      and VMN did not differ significantly under the same conditions. CONCLUSIONS: The
      VMN produced more fine particles of salbutamol/ipratropium, and the drug particle
      size clearly increased in the presence of heat and humidification.

PMID- 29054518
TI  - A Statistical approach to optimize the production of Polyhydroxyalkanoates from
      Wickerhamomyces anomalus VIT-NN01 using Response Surface Methodology.
AB  - Polyhydroxyalkanoates (PHAs) are three-level group of biodegradable polymers and
      attractive substitutes over conventional plastics to avoid the pollution
      problems. The yeast strain isolated from sugarcane juice, identified as
      Wickerhamomyces anomalus VIT-NN01, was used for the production of
      polyhydroxyalkanoates (PHA). Response surface methodology (RSM), three-level six
      variables Box-Behnken design (BBD), was employed to optimize the factors such as
      pH 8.0, temperature 37 degrees C, sugarcane molasses (35g/L) supplemented with co
      substrate palm oil (0.5%),corn steep liquor (2%) after a period of 96h of
      incubation for the maximum yield (19.50+/-0.3g/L) of PHA. It was well in close
      agreement with the predicted value obtained by RSM model yield (19.55+/
      0.1g/L).Characterization of the extracted polymer was done using FTIR, GC-MS,
      XRD, TGA and AFM analysis. NMR spectroscopic analysis revealed that the
      biopolymer was poly (3-hydroxybutyrate-co-3-hydroxyvalerate), copolymer of PHA.
      This is the first report on optimization of PHA production using yeast strain
      isolated from natural sources.

PMID- 29054519
TI  - Nature derived scaffolds for tissue engineering applications: Design and
      fabrication of a composite scaffold incorporating chitosan-g-d,l-lactic acid and
      cellulose nanocrystals from Lactuca sativa L. cv green leaf.
AB  - Through exhaustive extraction via successive alkali and bleaching treatments
      cellulose was isolated from lettuce. The isolated cellulose was hydrolyzed using
      64wt% H2SO4 at 55 degrees C under constant stirring for 1h to obtain cellulose
      nanocrystals (CNCs). Characterizations such as SEM, TEM, FTIR, TGA and XRD were
      done in order to determine differences in the physico-chemical characteristics of
      cellulose after each treatment step. The isolated CNCs have mean dimensions of
      237+/-26, 33+/-12 and 32+/-7nm in length, thickness and height, respectively.
      These nanocrystals were incorporated to the formulations that were used to
      fabricate different chitosan-g-d,l-lactic acid (CgLA) scaffolds. Amide linkage
      formation between chitosan and lactic acid and further removal of water was
      facilitated by oven-drying under vacuum at 80 degrees C. Results show that an
      increase in the concentration of CNCs added, increase in porosity, degradability,
      drug release property and cell viability were observed from the fabricated
      composite scaffolds. These results can provide information on how nanofillers
      such as CNCs can alter the properties of tissue scaffolds through the chemical
      properties and interactions they provide. Moreover, these characteristics can
      give new properties that are necessary for certain tissue engineering
      applications.

PMID- 29054520
TI  - Anti-psoriatic and toxicity evaluation of methotrexate loaded chitin nanogel in
      imiquimod induced mice model.
AB  - Methotrexate loaded chitin nanogel (MCNG) was formulated for its topical use in
      psoriasis. MCNG was characterized by DLS, TEM and FTIR. The MCNG particles were
      spherical in shape with size of 196+/-14nm, having surface charge of +9.21+/-0.42
      mv. MCNG exhibited greater swelling and drug release at acidic pH than neutral
      and alkaline conditions. The treatment with MCNG showed significant level of
      toxicity on HaCaT and THP-1 cells and was taken up well by HaCaT cells as
      revealed by fluorescent microscopy. MCNGs exhibited significant anti-inflammatory
      activity as revealed by the inhibitory effects observed on the activity of COX-2
      and LOX-5 enzymes expressed in THP-1 cells. Skin permeation studies revealed an
      increased trasdermal flux of methotrexate from MCNG with loosened stratum corneum
      and other epidermal layers of skin in comparison with control methotrexate
      solution treated samples. Significant anti-psoriatic efficacy on imiquimod (IMQ)
      induced model of psoriasis without any dermal and systemic toxicities suggest
      that it as an ideal delivery platform for topical delivery of methotrexate in
      psoriasis. Thus it is expected to become a better alternative for the oral
      delivery of methotrexate in the selected disease.

PMID- 29054521
TI  - Computational simulations and experimental validation of structure-
      physicochemical properties of pristine and functionalized graphene: Implications
      for adverse effects on p53 mediated DNA damage response.
AB  - Recent reports indicated DNA damaging potential of few-layer graphene in human
      cell systems. Here, we used computational technique to understand the interaction
      of both pristine (pG) or carboxyl functionalized graphene (fG) of different sizes
      (1, 6, and 10nm) with an important DNA repair protein p53. The molecular docking
      study revealed strong interaction between pG and DNA binding domains (DBD) of p53
      with binding free energies (BE) varying from -12.0 (1nm) to -34 (6nm)kcal/mol,
      while fG showed relatively less interaction with BE varying from -6.7 (1nm) to 
      11.1 (6nm)kcal/mol. Most importantly, pG or fG bound p53-DBDs could not bind to
      DNA. Further, microarray analysis of human primary endothelial cells revealed
      graphene intervention on DNA damage and its structure-properties effect using
      comet assay studies. Thus, computational and experimental results revealed the
      structure-physicochemical property dependent adverse effects of graphene in DNA
      repair protein p53.

PMID- 29054522
TI  - Antimicrobial activity of a newly identified Kazal-type serine proteinase
      inhibitor, CcKPI1, from the jellyfish Cyanea capillata.
AB  - In this study, we reported a jellyfish-derived Kazal-type serine protease
      inhibitor, named CcKPI1, from Cyanea capillata. CcKPI1 has a calculated molecular
      mass of 19.02kDa and contains three typical Kazal domains. Soluble recombinant
      CcKPI1 (rCcKPI1) was successfully expressed and purified. rCcKPI1 exhibited
      significant inhibitory activities against elastase, subtilisin A and proteinase
      K, but not against trypsin or chymotrypsin. Kinetic studies showed that all of
      the inhibitory effects of rCcKPI1 were competitive, indicating that it may be a
      microbial serine protease inhibitor and can exhibit antimicrobial activity. As
      predicted, rCcKPI1 directly bound to various microorganisms, including the Gram
      positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative
      bacteria Escherichia coli, marine pathogenic vibrios Vibrio vulnificus, Vibrio
      cholerae, Vibrio natriegens, Vibrio mimicus, Vibrio alginolyticus and Vibrio
      parahaemolyticus, and fungi Candida albicans, Candida parapsilokis and Candida
      glabrata. In addition, rCcKPI1 inhibited the growth of most of the tested
      microorganisms that it bound to. These findings indicate that CcKPI1 possesses
      marked antibacterial and antifungal activities and may play an important role in
      the immune defence of C. capillata, providing a novel view for the understanding
      of the immune system of jellyfish and also facilitating future research on
      antimicrobial agents from marine natural products.

PMID- 29054523
TI  - Glandular hair constituents of Mallotus philippinensis Muell. fruit act as
      tyrosinase inhibitors: Insights from enzyme kinetics and simulation study.
AB  - The glandular hair extracts from the fruit rind of Mallotus philippinensis Muell.
      is employed to treat various skin infections, however the anti-tyrosinase
      activity remains unknown. Hence the present study inspected on the anti
      melanogenic activity of M. philippinensis constituents. Lineweaver Burk plot
      revealed mixed inhibition for Rottlerin; non-competitive type of inhibition for
      mallotophilippen A and B respectively. Thermodynamic studies resulted in static
      quenching forming ground state complex with higher binding constant temperature
      dependently. Fluorescence and circular dichroism study implicated conformational
      change in secondary and tertiary structure of tyrosinase. Molecular docking
      suggests rottlerin has high binding affinity to the active site pocket of
      tyrosinase. Simulation study further proved that the compactness of inhibitor
      with tyrosinase by hydrogen bonding influenced the stability of the enzyme.
      Depigmentation efficacy is further proved in Aspergillus niger spores. Thus our
      findings delineate that rottlerin could be utilized as a depigmentation agent in
      food pharmaceutical and agricultural industries.

PMID- 29054524
TI  - The effects of concentration and heating-cooling rate on rheological properties
      of Plantago lanceolata seed mucilage.
AB  - In this study, the effect of concentration (0.5, 1, 1.5 and 2%) and heating
      cooling rate (1, 5 and 10  degrees C min-1) on the rheological properties of
      Plantago lanceolata seed mucilage (PLSM) solutions were investigated. It was
      observed that the gum dispersions exhibited viscoelastic properties under the
      given conditions. Mechanical spectra of PLSM were classified as weak gels based
      on the frequency sweep, complex viscosity (eta*) and tan delta results. All
      variables had significant impacts on the rheological parameters. Chemical and
      monosaccharide compositions were also determined to provide more structural
      information. The results revealed that PLSM had high total sugar content
      (87.35%), and it is likely an arabinoxylomannan-type polysaccharide.

PMID- 29054525
TI  - Development of a tannic acid cross-linking process for obtaining 3D porous cell
      laden collagen structure.
AB  - Cell-printing is an emerging technique that enables to build a customized
      structure using biomaterials and living cells for various biomedical
      applications. In many biomaterials, alginate has been widely used for rapid
      gelation, low cost, and relatively high processability. However,
      biocompatibilities enhancing cell adhesion and proliferation were limited, so
      that, to overcome this problem, an outstanding alternative, collagen, has been
      extensively investigated. Many factors remain to be proven for cell-printing
      applications, such as printability, physical sustainability after printing, and
      applicability of in vitro cell culture. This study proposes a cell-laden collagen
      scaffold fabricated via cell-printing and tannic acid (TA) crosslinking process.
      The effects of the crosslinking agent (0-3wt% TA) in the cell-laden collagen
      scaffolds on physical properties and cellular activities using preosteoblasts
      (MC3T3-E1) were presented. Compared to the cell-laden collagen scaffold without
      TA crosslinking, the scaffold with TA crosslinking was significantly enhanced in
      mechanical properties, while reasonable cellular activities were observed.
      Concisely, this study introduces the possibility of a cell-printing process using
      collagen and TA crosslinking and in vitro cell culture for tissue regeneration.

PMID- 29054526
TI  - One-step synthesis of starch-silver nanoparticle solution and its application to
      antibacterial paper coating.
AB  - Antibacterial starch-silver nanoparticles (ST-AgNPs) for use as coating solutions
      were prepared in a single step by ultrasonicating a mixture of starch, silver
      nitrate, and distilled water. The starch was used as an eco-friendly and
      inexpensive reducing agent. UV-vis spectra and transmission electron microscopy
      indicated that our single-step process was effective for synthesizing starch
      based coating solution with AgNPs. Further, the as-prepared coating solution with
      AgNPs was applied to expand the application of paper for antibacterial packaging.
      The starch-coated paper with AgNPs showed not only highly enhanced oil
      resistance, but also excellent antibacterial activity, making our biodegradable
      starch-coated paper with AgNPs highly feasible for packaging applications.

PMID- 29054527
TI  - Chitosan-based particulate systems for the delivery of mucosal vaccines against
      infectious diseases.
AB  - Given that most pathogens enter the body at mucosal surfaces for infection and
      mucosal immune responses act as the first line of defense against the invading
      pathogens, mucosal vaccination is the most effective method to prevent infectious
      diseases. However, the development of mucosal vaccines requires an efficient
      antigen delivery system which should protect the antigens from physical
      elimination and enzymatic degradation, target mucosal inductive sites, and
      appropriately stimulate the mucosal and systemic immunity. Accordingly, polymeric
      particles have garnered much attention because the physicochemical properties of
      polymers can be adjusted to resolve the issues associated with mucosal vaccine
      delivery. Particularly, chitosan-based polymeric carriers are the most promising
      vehicles for mucosal vaccine delivery because chitosan is biodegradable,
      biocompatible and mucoadhesive in nature. Similarly, chitosan can be modified
      with chemical and biological molecules to develop delivery carriers for
      controlled or targeted therapy. Moreover, they can be converted to various
      formulations, such as solid, liquid and gel, with a wide range of particle sizes.
      In this review, we highlight and discuss advances in the development of chitosan
      based particulate systems, specifically for the delivery of mucosal vaccines
      against infections.

PMID- 29054528
TI  - Using two-site binding models to analyze microscale thermophoresis data.
AB  - The emergence of microscale thermophoresis (MST) as a technique for determining
      the dissociation constants for bimolecular interactions has enabled these
      quantities to be measured in systems that were previously difficult or
      impracticable. However, most models for analyses of these data featured the
      assumption of a simple 1:1 binding interaction. The only model widely used for
      multiple binding sites was the Hill equation. Here, we describe two new MST
      analytic models that assume a 1:2 binding scheme: the first features two
      microscopic binding constants (KD(1) and KD(2)), while the other assumes symmetry
      in the bivalent molecule, culminating in a model with a single macroscopic
      dissociation constant (KD,M) and a single factor (alpha) that accounts for
      apparent cooperativity in the binding. We also discuss the general applicability
      of the Hill equation for MST data. The performances of the algorithms on both
      real and simulated data are assessed, and implementation of the algorithms in the
      MST analysis program PALMIST is discussed.

PMID- 29054529
TI  - Development of amide-based fluorescent probes for selective measurement of
      carboxylesterase 1 activity in tissue extracts.
AB  - Carboxylesterases are well known for their role in the metabolism of xenobiotics.
      However, recent studies have also implicated carboxylesterases in regulating a
      number of physiological processes including metabolic homeostasis and macrophage
      development, underlying the need to quantify them individually. Unfortunately,
      current methods for selectively measuring the catalytic activity of individual
      carboxylesterases are not sufficiently sensitive to support many biological
      studies. In order to develop a more sensitive and selective method to measure the
      activity of human carboxylesterase 1 (hCE1), we generated and tested novel
      substrates with a fluorescent aminopyridine leaving group. hCE1 showed at least a
      10-fold higher preference for the optimized substrate 4-MOMMP than the 13 other
      esterases tested. Because of the high stability of 4-MOMMP and its hydrolysis
      product, this substrate can be used to measure esterase activity over extended
      incubation periods yielding a low picogram (femtomol) limit of detection. This
      sensitivity is comparable to current ELISA methods; however, the new assay
      quantifies only the catalytically active enzyme facilitating direct correlation
      to biological processes. The method described herein may allow hCE1 activity to
      be used as a biomarker for predicting drug pharmacokinetics, early detection of
      hepatocellular carcinoma, and other disease states where the activity of hCE1 is
      altered.

PMID- 29054530
TI  - A molecular morphometric approach to diabetic kidney disease can link structure
      to function and outcome.
AB  - Diabetic kidney disease is the leading cause of kidney failure. However, studies
      of molecular mechanisms of early kidney damage are lacking. Here we examined for
      possible linkage between transcriptional regulation and quantitative structural
      damage in early diabetic kidney disease in Pima Indians with type 2 diabetes.
      Tissue obtained from protocol kidney biopsies underwent genome-wide compartment
      specific gene expression profiling and quantitative morphometric analysis. The
      ultrastructural lesion most strongly associated with transcriptional regulation
      was cortical interstitial fractional volume (VvInt), an index of tubule
      interstitial damage. Transcriptional co-expression network analysis identified
      1843 transcripts that correlated significantly with VvInt. These transcripts were
      enriched for pathways associated with mitochondrial dysfunction, inflammation,
      migratory mechanisms, and tubular metabolic functions. Pathway network analysis
      identified IL-1beta as a key upstream regulator of the inflammatory response and
      five transcription factors cooperating with p53 to regulate metabolic functions.
      VvInt-associated transcripts showed significant correlation with the urine
      albumin to creatinine ratio and measured glomerular filtration rate 10 years
      after biopsy, establishing a link between the early molecular events and long
      term disease progression. Thus, molecular mechanisms active early in diabetic
      kidney disease were revealed by correlating intrarenal transcripts with
      quantitative morphometry and long-term outcomes. This provides a starting point
      for identification of urgently needed therapeutic targets and non-invasive
      biomarkers of early diabetic kidney disease.

PMID- 29054531
TI  - The ammonia transporter RhCG modulates urinary acidification by interacting with
      the vacuolar proton-ATPases in renal intercalated cells.
AB  - Ammonium, stemming from renal ammoniagenesis, is a major urinary proton buffer
      and is excreted along the collecting duct. This process depends on the
      concomitant secretion of ammonia by the ammonia channel RhCG and of protons by
      the vacuolar-type proton-ATPase pump. Thus, urinary ammonium content and urinary
      acidification are tightly linked. However, mice lacking Rhcg excrete more
      alkaline urine despite lower urinary ammonium, suggesting an unexpected role of
      Rhcg in urinary acidification. RhCG and the B1 and B2 proton-ATPase subunits
      could be co-immunoprecipitated from kidney. In ex vivo microperfused cortical
      collecting ducts (CCD) proton-ATPase activity was drastically reduced in the
      absence of Rhcg. Conversely, overexpression of RhCG in HEK293 cells resulted in
      higher proton secretion rates and increased B1 proton-ATPase mRNA expression.
      However, in kidneys from Rhcg-/- mice the expression of only B1 and B2 subunits
      was altered. Immunolocalization of proton-ATPase subunits together with immuno
      gold detection of the A proton-ATPase subunit showed similar localization and
      density of staining in kidneys from Rhcg+/+ and Rhcg-/-mice. In order to test for
      a reciprocal effect of intercalated cell proton-ATPases on Rhcg activity, we
      assessed Rhcg and proton-ATPase activities in microperfused CCD from Atp6v1b1-/-
      mice and showed reduced proton-ATPase activity without altering Rhcg activity.
      Thus, RhCG and proton-ATPase are located within the same cellular protein
      complex. RhCG may modulate proton-ATPase function and urinary acidification,
      whereas proton-ATPase activity does not affect RhCG function. This mechanism may
      help to coordinate ammonia and proton secretion beyond physicochemical driving
      forces.

PMID- 29054532
TI  - A randomized clinical trial indicates that levamisole increases the time to
      relapse in children with steroid-sensitive idiopathic nephrotic syndrome.
AB  - Levamisole has been considered the least toxic and least expensive steroid
      sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic
      syndrome (SSINS). However, evidence for this is limited as previous randomized
      clinical trials were found to have methodological limitations. Therefore, we
      conducted an international multicenter, placebo-controlled, double-blind,
      randomized clinical trial to reassess its usefulness in prevention of relapses in
      children with SSINS. The efficacy and safety of one year of levamisole treatment
      in children with SSINS and frequent relapses were evaluated. The primary analysis
      cohort consisted of 99 patients from 6 countries. Between 100 days and 12 months
      after the start of study medication, the time to relapse (primary endpoint) was
      significantly increased in the levamisole compared to the placebo group (hazard
      ratio 0.22 [95% confidence interval 0.11-0.43]). Significantly, after 12 months
      of treatment, six percent of placebo patients versus 26 percent of levamisole
      patients were still in remission. During this period, the most frequent serious
      adverse event (four of 50 patients) possibly related to levamisole was
      asymptomatic moderate neutropenia, which was reversible spontaneously or after
      treatment discontinuation. Thus, in children with SSINS and frequent relapses,
      levamisole prolonged the time to relapse and also prevented recurrence during one
      year of treatment compared to prednisone alone. However, regular blood controls
      are necessary for safety issues.

PMID- 29054533
TI  - Corrigendum to "Plasmid dynamics in Vibrio parahaemolyticus strains related to
      shrimp Acute Hepatopancreatic Necrosis Syndrome (AHPNS)" [Infect. Genet. Evol.
      (2017) 51: 211-218].

PMID- 29054534
TI  - Mechanisms driving the ageing heart.
AB  - Cardiovascular disease (CVD) is the leading cause of death globally. One of the
      main risk factors for CVD is age, however the biological processes that occur in
      the heart during ageing are poorly understood. It is therefore important to
      understand the fundamental mechanisms driving heart ageing to enable the
      development of preventions and treatments targeting these processes. Cellular
      senescence is often described as the irreversible cell-cycle arrest which occurs
      in somatic cells. Emerging evidence suggests that cellular senescence plays a key
      role in heart ageing, however the cell-types involved and the underlying
      mechanisms are not yet elucidated. In this review we discuss the current
      understanding of how mechanisms known to contribute to senescence impact on heart
      ageing and CVD. Finally, we evaluate recent data suggesting that targeting
      senescent cells may be a viable therapy to counteract the ageing of the heart.

PMID- 29054535
TI  - Adipose tissue inflammation in aging.
AB  - Adipose tissue has traditionally been viewed as an organ of interest within
      studies of obesity and diet-associated metabolic disorders. However, as studies
      reveal the role white adipose tissue plays as an energy storage, a lipid
      metabolism site, and an adipokine secretor, it has become recognized as an organ
      of importance for metabolic health in both the young obese and the old obese.
      Within the realms of aging research, the pursuit of senolytics has taken the
      field's spotlight, where the clearance of senescent cells has shown to attenuate
      aspects of age-related disorders. More interestingly, these senolytics have also
      revealed that these senescent cells, specifically p16Ink4a cells, accumulate
      within adipose tissue, skeletal muscles, and eye (Baker et al., 2011). These
      results implicate the importance of adipose tissue inflammation in aging and
      widen the discussion on how senescent cells among other immune and non-immune
      cells cross paths to influence an organism's lifespan and healthspan.

PMID- 29054536
TI  - Decreasing body mass index is associated with cerebrospinal fluid markers of
      Alzheimer's pathology in MCI and mild dementia.
AB  - BACKGROUND: Several studies have identified an association between body mass
      index (BMI) and the incidence and severity of Alzheimer's disease (AD) but this
      relationship is not fully understood. OBJECTIVE: The primary objective of this
      study was to assess the possible association between BMI and cerebrospinal fluid
      (CSF) biomarkers of AD pathology in subjects with normal cognition and cognitive
      impairment. The secondary objective was to test whether BMI may contribute to
      improve the accuracy of a clinical model to predict AD pathology in memory clinic
      patients with cognitive impairment. METHOD: One hundred and seven elderly
      subjects with cognitive impairment (91 memory clinic patients with mild cognitive
      impairment [MCI] and 16 with dementia of AD type) and 55 cognitively healthy
      volunteers were included in this study. All subjects received a comprehensive
      clinical and neuropsychological evaluation and a lumbar puncture for CSF
      biomarker analysis. Multiple linear regressions and receiver operating
      characteristic (ROC) analyses were carried out to assess the association between
      BMI and the CSF biomarkers of AD pathology. RESULTS: BMI was positively
      correlated with the CSF levels of Abeta42 and negatively with tau and P-tau181 in
      participants with cognitive impairment. The associations were independent of age,
      sex, educational level, type and severity of cognitive impairment,
      cerebrovascular risk factors and the presence of the APOEepsilon4 allele.
      Furthermore, BMI significantly improved the sensitivity and specificity of a
      multi-factorial model to predict the presence of an AD CSF biomarker profile.
      CONCLUSION: Lower BMI is associated with cerebral AD pathology rather than with
      cognitive impairment in elderly subjects with MCI and mild dementia. Along with
      other clinical factors, decreasing BMI may help the clinician to identify
      patients with cognitive impairment due to AD.

PMID- 29054537
TI  - Calcium signaling at the endoplasmic reticulum: fine-tuning stress responses.
AB  - Endoplasmic reticulum (ER) calcium signaling is implicated in a myriad of
      coordinated cellular processes. The ER calcium content is tightly regulated as it
      allows a favorable environment for protein folding, in addition to operate as a
      major reservoir for fast and specific release of calcium. Altered ER homeostasis
      impacts protein folding, activating the unfolded protein response (UPR) as a
      rescue mechanism to restore proteostasis. ER calcium release impacts
      mitochondrial metabolism and also fine-tunes the threshold to undergo apoptosis
      under chronic stress. The global coordination between UPR signaling and energetic
      demands takes place at mitochondrial associated membranes (MAMs), specialized
      subdomains mediating interorganelle communication. Here we discuss current models
      explaining the functional relationship between ER homeostasis and various
      cellular responses to coordinate proteostasis and metabolic maintenance.

PMID- 29054538
TI  - Lower mitochondrial dysfunction in survivor septic patients with mitochondrial
      DNA haplogroup JT.
AB  - OBJECTIVE: The comparison on mitochondrial function between severe septic
      patients and healthy control subjects according to mitochondrial deoxyribonucleic
      acid (mtDNA) haplogroup has not been previously reported; and this was the
      objective of the current study. METHODS: Prospective, multicenter, observational
      study. We obtained blood samples from 198 severe septic patients at days 1, 4 and
      8 of severe sepsis diagnosis and from 96 sex- and age-matched healthy controls to
      determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific
      activity. The endpoint of the study was 30-day mortality. RESULTS: We included
      198 severe septic patients (38 with mtDNA haplogroup JT and 160 with mtDNA
      haplogroup non-JT) and 96 healthy control subjects (16 with mtDNA haplogroup JT
      and 80 with mtDNA haplogroup non-JT). We have no found statistically significant
      differences in platelet CIV specific activity between healthy controls and
      survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of
      severe sepsis diagnosis; and the remaining severe septic patients showed lower
      platelet CIV specific activity than healthy controls with the same mtDNA
      haplogroup. CONCLUSIONS: The new finding of our study was that survivor severe
      septic patients and healthy controls with mtDNA haplogroup JT showed no different
      platelet Civ specific activity.

PMID- 29054539
TI  - Observations on "Native valve endocarditis caused by Kocuria kristinae".

PMID- 29054540
TI  - Do sport-related concussions result in long-term cognitive impairment? A review
      of event-related potential research.
AB  - Sport-related concussions have become a major public health concern although the
      long-term effects on cognitive function remain largely unknown. Event-related
      potentials (ERPs) are ideal for studying the long-term impact of sport-related
      concussions, as they have excellent temporal precision and provide insight that
      cannot be obtained from behavioral or neuropsychological measures alone. We
      reviewed all available published studies that have used stimulus or response
      locked ERPs to document cognitive control processes in individuals with a history
      of concussion. Collectively, cross-sectional evidence suggests consistent
      reductions in P3 amplitude in previously concussed individuals, as well as a
      possible impairment in cognitive processing speed (P3 latency) and error
      monitoring processes (ERN). The persistent neurophysiological changes found may
      be related to the number of previous concussions sustained and the time since
      injury. Future studies incorporating prospective research designs are warranted
      before definitive statements can be offered regarding the long-term impact of
      sport-related concussions on cognitive control.

PMID- 29054541
TI  - A quantitative assessment of the membrane-integral sub-proteome of a bacterial
      magnetic organelle.
AB  - : Magnetotactic bacteria produce chains of complex membrane-bound organelles that
      direct the biomineralization of magnetic nanoparticles and serve for magnetic
      field navigation. These magnetosome compartments have recently emerged as a model
      for studying the subcellular organization of prokaryotic organelles. Previous
      studies indicated the presence of specific proteins with various functions in
      magnetosome biosynthesis. However, the exact composition and stoichiometry of the
      magnetosome subproteome have remained unknown. In order to quantify and
      unambiguously identify all proteins specifically targeted to the magnetosome
      membrane of the Alphaproteobacterium Magnetospirillum gryphiswaldense, we
      analyzed the protein composition of several cellular fractions by semi
      quantitative mass spectrometry. We found that nearly all genuine magnetosome
      membrane-integral proteins belong to a well-defined set of previously identified
      proteins encoded by gene clusters within a genomic island, indicating a highly
      controlled protein composition. Magnetosome proteins were present in different
      quantities with up to 120 copies per particle as estimated by correlating our
      results with available quantitative Western blot data. This high abundance
      suggests an unusually crowded protein composition of the membrane and a tight
      packing with transmembrane domains of integral proteins. Our findings will help
      to further define the structure of the organelle and contribute to the
      elucidation of magnetosome biogenesis. BIOLOGICAL SIGNIFICANCE: Magnetosomes are
      one of the most complex bacterial organelles and consist of membrane-bounded
      crystals of magnetic minerals. The exact composition and stoichiometry of the
      associated membrane integral proteins are of major interest for a deeper
      understanding of prokaryotic organelle assembly; however, previous proteomic
      studies failed to reveal meaningful estimations due to the lack of precise and
      quantitative data, and the inherently high degree of accumulated protein
      contaminants in purified magnetosomes. Using a highly sensitive mass
      spectrometer, we acquired proteomic data from several cellular fractions of a
      magnetosome producing magnetotactic bacterium and developed a comparative
      algorithm to identify all genuine magnetosome membrane-integral proteins and to
      discriminate them from contaminants. Furthermore, by combining our data with
      previously published quantitative Western blot data, we were able to model the
      protein copy number and density within the magnetosome membrane. Our results
      suggest that the magnetosome membrane is specifically associated with a small
      subset of integral proteins that are tightly packed within the lipid layer. Our
      study provides by far the most comprehensive estimation of magnetosomal protein
      composition and stoichiometry and will help to elucidate the complex process of
      magnetosome biogenesis.

PMID- 29054543
TI  - Outcomes of surgically treated distal radial fractures with associated triangular
      fibrocartilage complex injury.
AB  - STUDY DESIGN: Prospective cohort. INTRODUCTION: Clinical studies that evaluate
      the correlation between associated lesions of the triangular fibrocartilage
      complex (TFCC) and outcome of distal radial fractures expressed with the patient
      rated disability are missing. PURPOSE OF THE STUDY: To evaluate the outcomes of
      distal radius fractures associated with or without an injury of the TFCC.
      METHODS: Patients undergoing operative treatment for distal radial fracture were
      prospectively enrolled (n = 70). The TFCC was examined by wrist arthroscopy, and
      injuries were classified according to Palmer. Comparative analyses were performed
      on data from 45 patients with TFCC injury (the injured group) and 25 patients
      with an intact TFCC (the intact group). The outcome measures included The Patient
      Rated Wrist Evaluation (PRWE) and the Disabilities of the Arm, Shoulder and Hand
      (DASH) questionnaires, 3 and 12 months after injury. RESULTS: The TFCC was
      injured in 45 patients (64%). In patients with an intact TFCC, the mean total
      PRWE score was 27 (at 3 months) and 16 (at 12 months), whereas in patients with
      TFCC injury, it was 40 (at 3 months) and 24 (at 12 months). Mean DASH scores were
      26 and 13 for the intact group and 39 and 27 for the injured group at 3 and 12
      months, respectively. PRWE and DASH results showed significant difference at 3
      and 12 months when compared using the Mann-Whitney test. CONCLUSIONS: Disability
      outcomes were worse in patients with distal radial fracture where TFCC was
      injured. TFCC injuries are an important cofactor affecting the outcome of distal
      radial fractures.

PMID- 29054542
TI  - Cortical-hippocampal functional connectivity during covert consolidation sub
      serves associative learning: Evidence for an active "rest" state.
AB  - We studied modulation of undirected functional connectivity (uFC) in cortical
      hippocampal sub-networks during associative learning. Nineteen healthy
      individuals were studied (fMRI acquired on a Siemens Verio 3T), and uFC was
      studied between nodes in a network of regions identified by standard activation
      models based on bivariate correlational analyses of time series data. The
      paradigm alternated between Memory Encoding, Rest and Retrieval. "Rest" intervals
      promoted covert consolidation. Over the task, performance was broadly separable
      into linear (Early) and asymptomatic (Late) regimes, with late performance
      reflecting successful memory consolidation. Significant modulation of uFC was
      observed during periods of covert consolidation. The sub-networks which were
      modulated constituted connections between frontal regions such as the dorsal
      prefrontal cortex (dPFC) and dorsal anterior cingulate cortex (dACC), the medial
      temporal lobe (hippocampus, HPC), the superior parietal cortex (SPC) and the
      fusiform gyrus (FG). uFC patterns were dynamic in that sub-networks modulated
      during Early learning (dACC <-> SPC, dACC <-> FG, dPFC <-> HPC) were not
      identical to those modulated during Late learning (dACC <-> HPC, dPFC <-> FG, FG
      <-> SPC). Covert consolidation exerts systematic effects, and these results add
      to emerging evidence for the constructive role of the brain's "resting state" in
      potentiating action.

PMID- 29054544
TI  - [Abnormalities of DNA repair and gynecological cancers].
AB  - The demonstration of frequent defects in the DNA damage response in high grade
      ovarian cancer has paved the way for a new therapeutic approach aimed at
      exploiting this unique vulnerability. The efficacy of poly (ADP) ribose
      polymerase inhibitors (PARPi) in patients with homologous recombination (HR) DNA
      repair deficient ovarian cancer (OC) resulting from a BRCA1/2 mutation has
      provided the proof of concept for synthetic lethality. Thus, olaparib is now
      approved by the EMA as maintenance therapy after response to a platinum regimen
      for patients with recurrent, platinum-sensitive, high-grade serous, BRCA1/2
      mutated ovarian cancer. Furthermore, several recent trials in OC have
      demonstrated that the benefit of PARPi may not be limited to patients with BRCA
      mutations. These data, combined with genomic studies suggesting that a
      significant proportion of OC may harbor somatic and germline alterations in other
      HR genes open huge perspectives for exploiting DNA repair as a therapeutic
      strategy. The current priorities are to (i) determine whether new biomarkers of
      homologous recombination deficiency may identify the BRCA wild-type subset likely
      to derive benefit from PARPi; (ii) to determine whether the efficacy of PARPi can
      be improved by combinatorial strategies (with chemotherapy, radiotherapy,
      immunotherapy, anti-angiogenesis or DNA repair inhibitors) and (iii) to develop
      new approaches exploiting DNA repair deficiencies in ovarian and other
      gynecological tumors.

PMID- 29054545
TI  - CHAC2 is essential for self-renewal and glutathione maintenance in human
      embryonic stem cells.
AB  - Glutathione (GSH), the major non-enzymatic antioxidant, plays a critical role in
      cellular reactive oxygen species (ROS) neutralization. Moreover, GSH is required
      for the self-renewal maintenance of human embryonic stem cells (hESCs), and is
      highly accumulated in undifferentiated cells. Among 8 GSH biosynthesis-related
      enzymes, we found CHAC2 is highly enriched in undifferentiated hESCs. CHAC2
      downregulation in hESCs efficiently decreased the levels of GSH and blocked self
      renewal. The self-renewal of sh-CHAC2 cells can be rescued by GSH supplement.
      CHAC2 downregulation promoted mesoderm differentiation and hampered both teratoma
      formation and the expression of Nrf2 and glutamate-cysteine ligase (GCL).
      Notably, CHAC1 knockdown restored the self-renewability of CHAC2-downregulated
      cells. Although both CHAC1 and CHAC2 purified protein alone showed the catalytic
      activities to GSH, our data extraordinarily revealed that CHAC2 prevented CHAC1
      mediated GSH degradation, which suggests that CHAC2 competes with CHAC1 to
      maintain GSH homeostasis. This is the first report to demonstrate that CHAC2 is
      critical for GSH maintenance and the novel roles of the CHAC family in hESC
      renewal.

PMID- 29054546
TI  - Identification and molecular characterization of spotted fever group rickettsiae
      in ticks collected from farm ruminants in Lebanon.
AB  - Tick-borne diseases have become a world health concern, emerging with increasing
      incidence in recent decades. Spotted fever group (SFG) rickettsiae are tick-borne
      pathogens recognized as important agents of human tick-borne diseases worldwide.
      In this study, 88 adult ticks from the species Hyalomma anatolicum, Rhipicephalus
      annulatus, Rh. bursa, Rh. sanguineus sensu lato, and Rh. turanicus, were
      collected from farm ruminants in Lebanon, and SFG rickettsiae were molecularly
      identified and characterized in these ticks. The screening showed a prevalence of
      68% for Rickettsia spp., including the species R. aeschlimannii, R. africae, R.
      massiliae and Candidatus R. barbariae, the latter considered an emerging member
      of the SFG rickettsiae. These findings contribute to a better knowledge of the
      distribution of these pathogens and demonstrate that SFG rickettsiae with public
      health relevance are found in ticks collected in Lebanon, where the widespread
      distribution of tick vectors and possible livestock animal hosts in contact with
      humans may favor transmission to humans. Few reports exist for some of the tick
      species identified here as being infected with SFG Rickettsia. Some of these tick
      species are proven vectors of the hosted rickettsiae, although this information
      is unknown for other of these species. Therefore, these results suggested further
      investigation on the vector competence of the tick species with unknown role in
      transmission of some of the pathogens identified in this study.

PMID- 29054547
TI  - Expression profile of Rhipicephalus microplus vitellogenin receptor during
      oogenesis.
AB  - The vitellogenin receptor (VgR), which belongs to the low-density lipoprotein
      receptors (LDLR) family, regulates the absorption of yolk protein accumulated in
      developing oocytes during oogenesis. In the present study, the full sequence of
      Rhipicephalus microplus VgR (RmVgR) and the partial sequence of Rhipicephalus
      appendiculatus VgR (RaVgR) ORF were determined and cloned. The RmVgR amino acid
      sequence contains the five highly conserved structural motifs characteristic of
      LDLR superfamily members, the same overall structure as observed in other
      species. Phylogenetic analysis separated VgRs in two major groups, corresponding
      to receptors from acarines and insects. Consistent with observations from other
      arthropods, RmVgR was specifically expressed in the ovarian tissue and its peak
      of expression occurs in females that are detaching from the host. Silencing with
      RmVgR dsRNA reduced VgR expression, which resulted in reduced fertility,
      evidenced by a decrease in the number of larvae. The present study confirms RmVgR
      is a specific receptor involved in yolk protein uptake and oocyte maturation in
      R. microplus, playing an important role in tick reproduction.

PMID- 29054548
TI  - [First description of Sclerotium coffeicola on African mahogany in Mexico].
AB  - A foliar disease was detected in the commercial plantation of Khaya senegalensis
      with three years of age in Huimanguillo, Tabasco, Mexico. Through the
      morphological and molecular characterization and the compliance of the Koch's
      postulates, it was concluded that the causal agent corresponds to the fungus
      Sclerotium coffeicola. This is the first report of S. coffeicola causing leaf
      spot on African mahogany in Mexico.

PMID- 29054549
TI  - [Growth and photochemical efficiency of photosystem ii in seedlings of two
      varieties of Capsicum annuum L. inoculated with rhizobacteria and arbuscular
      mycorrhizal fungi].
AB  - Plant growth promoting rhizobacteria (PGPR) and arbuscular mycorrhizal fungi
      (AMF) are a biological alternative for the sustainable management of Capsicum
      annuum L. This research work evaluated the effects of both PGPR and AMF on bell
      pepper and jalapeno pepper plants. Five bacterial strains isolated from several
      locations in Estado de Mexico were used: [P61 (Pseudomonas tolaasii), A46 (P.
      tolaasii), R44 (Bacillus pumilus), BSP1.1 (Paenibacillus sp.), and OLs-Sf5
      (Pseudomonas sp.)], and three treatments with AMF [H1 (consortium isolated from
      pepper crops in the State of Puebla), H2 (Rhizophagus intraradices), and H3
      (consortium isolated from the rhizosphere of lemon trees, State of Tabasco)]. In
      addition, a fertilized treatment (Steiner nutrient solution at 25%) and an
      unfertilized control were included. Seedlings of "Caloro" jalapeno pepper and
      "California Wonder" bell pepper were inoculated with AMF at seed sowing, and PGPR
      were inoculated after 15 days of seedling emergence; seedlings were grown under
      plant growth chamber conditions. P61 bacterium and H1 AMF consortia were the most
      effective microorganisms for jalapeno pepper whereas R44 bacterium and AMF H3 and
      H1 were the most effective for bell peppers, when compared to the unfertilized
      control. Furthermore, P61 and R44 bacteria showed beneficial effects on PSII
      efficiency.

PMID- 29054550
TI  - [MLVA analysis and virulence profile of community-acquired methicillin-resistant
      Staphylococcus aureus causing infections in Paraguayan children].
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is one
      of the first causes of skin and soft tissue infections, and can also produce
      severe diseases such as osteomyelitis and pneumonia. The aim of this descriptive
      study was to determine the SCCmec type and virulence profile and to study the
      genetic diversity by MLVA analysis of 21 CA-MRSA isolates that infected
      Paraguayan children in 2010. The SCCmec type and virulence factors were performed
      by PCR and genetic diversity by MLVA (multiple locus variable analysis). All the
      isolates carried SCCmec cassette iv. hla, hlb and sea genes were detected in
      28,6%, 9,5% and 4,8% respectively. The MLVA analysis showed high genetic
      diversity with congruent antibiotic resistance and virulence profiles. This study
      revealed the presence of CA-MRSA harbouring SCCmeciv with high genetic diversity,
      providing information not available in our country.

PMID- 29054551
TI  - [Mycoplasma hominis bacteremia. An underestimated etiological agent].
AB  - : Mycoplasma hominis is a fastidious bacterium, which usually colonizes the lower
      urogenital tract and may cause systemic infections in neonates and genital
      infections in adults. It can also be the cause of serious extra-genital
      infections, mainly in immunosuppressed or predisposed subjects. CASE
      PRESENTATION: We describe a case of bacteremia caused by M. hominis in a
      previously healthy woman after uterine curettage due to incomplete abortion. M.
      hominis could be an underestimated cause of bacteremia in immunocompetent
      patients. Mycoplasma organisms have fastidious growth requirements, are often
      difficult to culture on a cell-free medium and have no cell wall. The
      conventional method for detection may fail. This is the first report of M.
      hominis isolation from a positive automated blood culture (BD BACTEC, USA).

PMID- 29054554
TI  - Second look arthroscopic evaluation of repaired radial/oblique tears of the
      midbody of the lateral meniscus in stable knees.
AB  - BACKGROUND: Radial/oblique tears of the midbody of the lateral meniscus
      significantly impair the ability of the meniscus to withstand the tibiofemoral
      load, requiring meniscal repair. However, healing status after meniscal repair
      has not been fully elucidated. This study aimed to evaluate arthroscopic findings
      after inside-out suture repair for isolated radial/oblique tears of the midbody
      of the lateral meniscus. METHODS: From 2011 to 2015, 18 consecutive patients with
      isolated radial/oblique tears of the midbody of the lateral meniscus underwent
      arthroscopic inside-out repair with the tie-grip suture technique. All knees were
      stable with no previous surgery. All patients were evaluated by second-look
      arthroscopy at six months postoperatively. Activities including jogging were not
      allowed until meniscal status was evaluated arthroscopically. To analyze factors
      associated with healing rates, age, time from injury to initial surgery, and tear
      zone were compared. RESULTS: Second-look arthroscopy revealed complete healing in
      four (22%) patients, partial healing in seven (39%), and failure to heal in seven
      (39%). Significant differences were observed for tear zone (p < 0.0001), but not
      for age and timing of repair. CONCLUSIONS: Arthroscopic evaluation revealed that
      inside-out repair with the tie-grip suture technique for isolated radial/oblique
      tears of the midbody of the lateral meniscus achieved complete or partial healing
      only in 61% of patients. Satisfactory results were observed particularly in
      patients with tears extending to the vascular zone, whereas those with tears in
      the avascular zone failed to achieve healing. Therefore, the operative indication
      of inside-out repair for radial/oblique tears of the midbody of the lateral
      meniscus might be limited to tears extending into the vascular zone. Given that
      39% of cases were arthroscopically considered a failure even if patients
      complained of no symptoms in daily life, decisions should be made carefully to
      allow patients to return to sports activities.

PMID- 29054553
TI  - Long-term results of a prospective study of anterior decompression with fusion
      and posterior decompression with laminoplasty for treatment of cervical
      spondylotic myelopathy.
AB  - BACKGROUND: There have been no prospective studies comparing anterior surgery and
      posterior method in terms of long-term outcomes. The purposes of this study is to
      clarify whether there is any difference in long-term clinical and radiologic
      outcomes of anterior decompression with fusion (ADF) and laminoplasty (LAMP) for
      the treatment of cervical spondylotic myelopathy (CSM). METHODS: Ninety-five
      patients were prospectively treated with ADF or LAMP for CSM in our hospital from
      1996 through 2003. On alternate years, patients were enrolled to receive ADF
      (1997, 1999, 2001, and 2003: ADF group, n = 45) or LAMP (1996, 1998, 2000, and
      2002: LAMP group, n = 50). We excluded 19 patients who died during follow-up, and
      25 who were lost to follow-up. Clinical outcomes were evaluated by the recovery
      rate of the Japanese Orthopaedic Association (JOA) score between the two groups.
      Sagittal alignment of the C2-7 lordotic angle and range of motion (ROM) in
      flexion and extension on plain X-ray were measured. RESULTS: Mean age at the time
      of surgery was 58.3 years in the ADF group and 57.9 years in the LAMP group. Mean
      preoperative JOA score was 10.0 and 10.5, respectively. Mean recovery rate of the
      JOA score at 3-5 years postoperatively was significantly higher in the ADF group
      (p < 0.05). Reoperation was required in 1 patient for pseudarthrosis and in 1
      patient for recurrence of myelopathy in the ADF group; no patient in the LAMP
      group underwent a second surgery. There was a significant difference in
      maintenance of the lordotic angle in the ADF group compared with the LAMP group
      (p < 0.05), but not in ROM. CONCLUSIONS: Both ADF and LAMP provided similar good
      outcomes at 10-year time-point whereas ADF could achieve more satisfactory
      outcomes and better sagittal alignment at the middle-term. However, the incidence
      of reoperation and complication in the ADF group were higher than those in the
      LAMP group. STUDY DESIGN: A prospective comparative study (not randomized).

PMID- 29054552
TI  - Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic
      and clinical studies of the brain and periphery.
AB  - Oxytocin (OT) and arginine-vasopressin (AVP) act in the brain to regulate social
      cognition/social behavior and in the periphery to influence a variety of
      physiological processes. Although the chemical structures of OT and AVP as well
      as their receptors are quite similar, OT and AVP can have distinct or even
      opposing actions. Here, we review the increasing body of evidence that
      exogenously administered and endogenously released OT and AVP can activate each
      other's canonical receptors (i.e., cross-talk) and examine the possibility that
      receptor cross-talk following the synaptic and non-synaptic release of OT and AVP
      contributes to their distinct roles in the brain and periphery. Understanding the
      consequences of cross-talk between OT and AVP receptors will be important in
      identifying how these peptides control social cognition and behavior and for the
      development of drugs to treat a variety of psychiatric disorders.

PMID- 29054556
TI  - Role of biochar as an additive in organic waste composting.
AB  - The use of biochar in organic waste composting has attracted interest in the last
      decade due to the environmental and agronomical benefits obtained during the
      process. Biochar presents favourable physicochemical properties, such as large
      porosity, surface area and high cation exchange capacity, enabling interaction
      with major nutrient cycles and favouring microbial growth in the composting pile.
      The enhanced environmental conditions can promote a change in the microbial
      communities that can affect important microbially mediated biogeochemical cycles:
      organic matter degradation and humification, nitrification, denitrification and
      methanogenesis. The main benefits of the use of biochar in composting are
      reviewed in this article, with special attention to those related to the process
      performance, compost microbiology, organic matter degradation and humification,
      reduction of N losses and greenhouse gas emissions and fate of heavy metals.

PMID- 29054555
TI  - Evidence-based guidelines for supportive care of patients with Ebola virus
      disease.
AB  - The 2013-16 Ebola virus disease outbreak in west Africa was associated with
      unprecedented challenges in the provision of care to patients with Ebola virus
      disease, including absence of pre-existing isolation and treatment facilities,
      patients' reluctance to present for medical care, and limitations in the
      provision of supportive medical care. Case fatality rates in west Africa were
      initially greater than 70%, but decreased with improvements in supportive care.
      To inform optimal care in a future outbreak of Ebola virus disease, we employed
      the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
      methodology to develop evidence-based guidelines for the delivery of supportive
      care to patients admitted to Ebola treatment units. Key recommendations include
      administration of oral and, as necessary, intravenous hydration; systematic
      monitoring of vital signs and volume status; availability of key biochemical
      testing; adequate staffing ratios; and availability of analgesics, including
      opioids, for pain relief.

PMID- 29054557
TI  - Optimization of hexanoic acid production in recombinant Escherichia coli by
      precise flux rebalancing.
AB  - The aim of this study is to demonstrate that rebalancing of metabolic fluxes at
      acetyl-CoA branch node can substantially improve the titer and productivity of
      hexanoic acid in recombinant Escherichia coli strains. First, a hexanoic acid
      producing E. coli strain was constructed by expressing genes encoding beta
      ketothiolase (BktB) from Cupriavidus necator and acetyl-CoA transferase (ACT)
      from Megasphaera sp. MH in a butyric acid producer strain. Next, metabolic flux
      was optimized at the acetyl-CoA branch node by fine-tuning the expression level
      of the gene for acetyl-CoA acetyltransferase (AtoB). Four synthetic 5'
      untranslated regions were designed for atoB using UTR Designer to modulate the
      expression level of the gene. Notably, the productivity of the optimized strain
      (14.7 mg/L/h) was the highest among recombinant E. coli strains in literature
      when using a similar inoculum size for fermentation. These results show that fine
      tuning the expression level of atoB is critical for production of hexanoic acid.

PMID- 29054559
TI  - The Influence of Reconstruction Kernel on Bone Mineral and Strength Estimates
      Using Quantitative Computed Tomography and Finite Element Analysis.
AB  - Quantitative computed tomography has been posed as an alternative imaging
      modality to investigate osteoporosis. We examined the influence of computed
      tomography convolution back-projection reconstruction kernels on the analysis of
      bone quantity and estimated mechanical properties in the proximal femur. Eighteen
      computed tomography scans of the proximal femur were reconstructed using both a
      standard smoothing reconstruction kernel and a bone-sharpening reconstruction
      kernel. Following phantom-based density calibration, we calculated typical bone
      quantity outcomes of integral volumetric bone mineral density, bone volume, and
      bone mineral content. Additionally, we performed finite element analysis in a
      standard sideways fall on the hip loading configuration. Significant differences
      for all outcome measures, except integral bone volume, were observed between the
      2 reconstruction kernels. Volumetric bone mineral density measured using images
      reconstructed by the standard kernel was significantly lower (6.7%, p < 0.001)
      when compared with images reconstructed using the bone-sharpening kernel.
      Furthermore, the whole-bone stiffness and the failure load measured in images
      reconstructed by the standard kernel were significantly lower (16.5%, p < 0.001,
      and 18.2%, p < 0.001, respectively) when compared with the image reconstructed by
      the bone-sharpening kernel. These data suggest that for future quantitative
      computed tomography studies, a standardized reconstruction kernel will maximize
      reproducibility, independent of the use of a quantitative calibration phantom.

PMID- 29054558
TI  - Serum lipid, lipoprotein and apolipoprotein profiles in workers exposed to low
      arsenic levels: Lipid profiles and occupational arsenic exposure.
AB  - Epidemiologic studies have reported that exposure to arsenic (As) is associated
      with higher risk of cardiovascular disease (i.e., coronary heart disease and
      peripheral arterial heart disease) and mortality. This cross-sectional study
      aimed to compare serum lipid, lipoprotein, and apolipoprotein profiles in workers
      exposed to As. The subjects of this study included 57 workers exposed to As and
      57 controls. Demographic characteristics and occupational information were
      collected through questionnaires. Exposure to As was assessed in indoor air of a
      workplace and determined using the creatinine values in the urine. Blood samples
      were collected using immunochemistry and nephelometry to measure the levels of
      total cholesterol (CHOL), triglycerides (TRIG), high-density lipoprotein (HDL),
      low-density lipoprotein (LDL), lipoprotein(a) (Lp(a)), apolipoprotein-A1 (Apo
      A1), and apolipoprotein-B (Apo-B). No significant difference in the demographic
      data was detected between the two groups. Urinary As concentration was
      significantly (p<0.001) higher in exposed subjects than in the controls (13.4+/
      6.1 and 4.4+/-6.1MUg/gCreat, respectively). No statistically significant
      differences were observed in CHOL, TRIG, HDL, and LDL concentrations between the
      two groups. Lp(a), Apo-B, and Apo-B/Apo-A1 ratio values were significantly higher
      and the Apo-A1 level was significantly lower in the exposed group than in the
      control subjects. Regression analysis highlighted a significant (p<0.001)
      association between urinary As and Lp(a), Apo-A1, and Apo-B concentration, and
      Apo-B/Apo-A1 ratio. This study revealed the influence of As on apolipoproteins,
      suggesting a potential risk of cardiovascular diseases in subjects exposed to low
      levels of As.

PMID- 29054560
TI  - Transcultural adaptation into Spanish of the Induction Compliance Checklist for
      assessing children's behaviour during induction of anaesthesia.
AB  - OBJECTIVE: Cross-cultural adaptation into Spanish of the Induction Compliance
      Checklist (ICC) for assessing children's behaviour during induction of
      anaesthesia. METHOD: A descriptive cross-sectional observational study was
      conducted on a sample of 81 children aged 2 to 12 years operated in an ambulatory
      surgery unit of a paediatric hospital in Barcelona. Adaptation by translation
      back translation of the tool and analysis of the scale's validity and
      reliability. RESULTS: Face validity of the tool was guaranteed through a
      discussion group and inter-observer reliability was evaluated, obtaining an
      intraclass correlation index of r = 0.956. CONCLUSIONS: The ICC scale validated
      for the Spanish population can be an effective tool for the presurgical
      evaluation of activities carried out to minimise children's anxiety. The ICC is
      an easy-to-use scale completed by operating room staff in one minute and would
      provide important information about children's behaviour, specifically during
      induction.

PMID- 29054561
TI  - The migratory factor as a determinant of health: A transcultural occupational
      health nursing intervention.
AB  - We present a clinical case in occupational health nursing where the worker was
      showing symptoms of stress caused by a change of residence and related factors at
      work. A nursing assessment was made following Leininger's theory of Care
      Diversity and Universality and Sunrise Model, considered suitable for the case.
      After the assessment, it was determined that the factors associated with the
      migratory event triggered the reported symptoms, and a care plan was drawn up
      with monthly telephone contact follow-up and reassessment at 3months. A holistic
      approach containing social and cultural elements, together with the use of
      standardised nurse language are very useful in cases such as the one presented.

PMID- 29054562
TI  - Exercise attenuates dexamethasone-induced hypertension through an improvement of
      baroreflex activity independently of the renin-angiotensin system.
AB  - Dexamethasone-induced hypertension may be caused by baroreflex alterations or
      renin-angiotensin system (RAS) exacerbation. Aerobic training has been
      recommended for hypertension treatment, but the mechanisms responsible for
      reduction of arterial pressure (AP) in dexamethasone (DEX) treated rats are still
      inconclusive.This study evaluated whether mechanisms responsible for training
      induced attenuation of hypertension involve changes in autonomic nervous system
      and in RAS components. Rats underwent aerobic training protocol on treadmill or
      were kept sedentary for 8 weeks. Additionally, animals were treated with DEX
      during the last 10 days of exercise. Body weight (BW), AP and baroreflex activity
      were analyzed. Tibialis anterior (TA), soleus (SOL) and left ventricle (LV) were
      collected for evaluation of RAS components gene expression and protein levels.
      Dexamethasone decreased BW (20%), caused TA atrophy (16%) and increased systolic
      AP (SAP, 16%) as well as decreased baroreflex activity. Training attenuated SAP
      increase and improved baroreflex activity, although it did not prevent DEX
      induced BW reduction and muscle atrophy. Neither DEX nor training caused
      expressive changes in RAS components. In conclusion, exercise training was
      effective in attenuating hypertension induced by DEX and this response may be
      mediated by a better autonomic balance through an improvement of baroreflex
      activity rather than changes in RAS components.

PMID- 29054563
TI  - Early diastolic septal movement in patients with myocarditis.
AB  - AIM: To evaluate early diastolic septal relaxation as a parameter in the
      diagnostic workup via cardiovascular magnetic resonance imaging (CMRI) in
      patients with myocarditis. MATERIALS AND METHODS: Early diastolic septal movement
      was evaluated (EDS) prospectively via frame-by-frame analysis in 255 consecutive
      patients with presenting signs of myocarditis and in 64 controls matched 4:1 for
      gender and age. ECG-triggered, T2-weighted, fast spin echo triple inversion
      recovery sequences and late gadolinium enhancement were obtained, as well as left
      ventricular (LV) function and dimensions in patients and controls. RESULTS: EDS
      was detected in 66.7% of the patients and 18.7% of the controls (p<0.001).
      Sensitivity was 69.4% and specificity 79.7%. Patients with EDS had a significant
      lower LV ejection fraction (LV-EF) of 61.1+/-0.6% and significant higher end
      diastolic volume (EDV) of 158.5+/-2.7 ml than in patients without EDS (LV-EF
      65.3+/-0.9%, p=0.0001; EDV 148.4+/-3.9 ml, p=0.04). A significant negative
      correlation was observed between LV-EF and EDS in patients, and a lower LV-EF
      correlated with a more frequent occurrence of EDS (r=-0.24, p=0.0001). Scar
      tissue was also more frequent in patients than controls (63.1% and 7.8%,
      p=0.007). CONCLUSIONS: EDS is a parameter obtained non-invasively by CMRI and is
      present in a high percentage of patients with myocarditis. Cardiac functional
      parameters are significantly altered in patients with EDS. EDS is a feasible
      parameter that can play an important role in the diagnosis of myocarditis.

PMID- 29054564
TI  - Extraction of mandibular third molars: proposal of a new scale of difficulty.
AB  - We evaluated the accuracy of a new scale of surgical difficulty for the
      extraction of impacted mandibular third molars, which includes consideration of
      previously underestimated variables. Two hundred patients with impacted third
      molars were enrolled, and a preoperative clinical and radiographic assessment of
      difficulty was made by an oral surgeon using the new index. Five oral surgeons
      with similar degrees of experience then evaluated the surgical difficulty during
      operation. The kappa test and weighted kappa were used to evaluate the level of
      agreement between the preoperative and postoperative evaluations. This was 0.73,
      which indicated a substantial concordance between the preoperative and
      postoperative assessments of difficulty indicated by the new scale. The linear
      weight of kappa was 0.8 and the quadratic weight 0.87. We recommend this new
      scale of surgical difficulty for the extraction of impacted third molars for use
      in clinical practice.

PMID- 29054565
TI  - Carbon Supply and the Regulation of Cell Wall Synthesis.
AB  - All plant cells are surrounded by a cell wall that determines the directionality
      of cell growth and protects the cell against its environment. Plant cell walls
      are comprised primarily of polysaccharides and represent the largest sink for
      photosynthetically fixed carbon, both for individual plants and in the
      terrestrial biosphere as a whole. Cell wall synthesis is a highly sophisticated
      process, involving multiple enzymes and metabolic intermediates, intracellular
      trafficking of proteins and cell wall precursors, assembly of cell wall polymers
      into the extracellular matrix, remodeling of polymers and their interactions, and
      recycling of cell wall sugars. In this review we discuss how newly fixed carbon,
      in the form of UDP-glucose and other nucleotide sugars, contributes to the
      synthesis of cell wall polysaccharides, and how cell wall synthesis is influenced
      by the carbon status of the plant, with a focus on the model species Arabidopsis
      (Arabidopsis thaliana).

PMID- 29054566
TI  - Pulmonary calcified masses and gastric tumor: Incomplete Carney's triad.

PMID- 29054567
TI  - Hydrogen Sulfide Specifically Alters NAD(P)H Quinone Dehydrogenase 1 (NQO1)
      Olfactory Neurons in the Rat.
AB  - The regions of the olfactory epithelium affected by hydrogen sulfide (H2S)
      toxicity in the rat present a striking similarity with the developmental
      olfactory zone 1 described in the mouse. This zone which is the only region
      containing neurons expressing NAD(P)H quinone dehydrogenase 1 (NQO1) is involved
      in complex behavioral responses in rodents, and other mammals, triggered by
      specific olfactory stimuli. We therefore sought to determine whether (1)
      olfactory neurons expressing NQO1 are located in the same regions in the rats and
      in the mice and (2) there is an overlap between olfactory neurons expressing this
      protein and those affected by the toxicity of H2S. Rats were exposed to H2S - 200
      ppm during 3 h, three consecutive days- and displayed symmetric acute segmental
      necrosis of the neurons and sustentacular cells of the olfactory epithelium in
      the dorsomedial nasal cavity. We found that expression of NQO1 in Sprague-Dawley
      rats spatially recapitulated that of the mouse. The degree of agreement or
      overlap between these two populations of neurons (necrosis vs. NQO1 expression)
      reached 80.2%. Although the underlying mechanisms accounted for the high
      sensitivity for NQO1 neurons -or the relative protection of non NQO1 neurons- to
      sulfide toxicity remain to be established, this observation is offering an
      intriguing approach that could be used to acutely suppress the pool of neural
      cells in olfactory zone I and to understand the mechanisms of toxicity and
      protection of other populations of neurons exposed to sulfide.

PMID- 29054568
TI  - Genetic epidemiology of ovarian cancer and prospects for polygenic risk
      prediction.
AB  - Epithelial ovarian cancer (EOC) is a heterogeneous disease with a major heritable
      component. The different histotypes of invasive disease - high grade serous,
      clear cell, endometrioid and mucinous - are associated with different underlying
      genetic susceptibility and epidemiological and lifestyle risk factors, all of
      which contribute to the different biology and clinical characteristics of each
      histotype. A combination of familial and population based sequencing studies, and
      genome wide association studies (GWAS) have identified a range of genetic
      susceptibility alleles for EOC comprising rare but highly penetrant genes (e.g.
      BRCA1, BRCA2) that are responsible for familial clustering of ovarian cancer
      cases; more moderate penetrance susceptibility genes (e.g. BRIP1, RAD51C/D,
      MSH6); and multiple common but low penetrance susceptibility alleles identified
      by GWAS. Identifying genetic risk alleles for ovarian cancer has had a
      significant impact on disease prevention strategies; for example it is now
      routine clinical practice for individuals with germline BRCA1 and BRCA2 mutations
      to undergo risk reducing salpingo-oophorectomy. Because ovarian cancers are
      commonly diagnosed at a late clinical stage when the prognosis is poor, the
      continued development of genetic risk prediction and prevention strategies will
      represent an important approach to reduce mortality due to ovarian cancer.
      Advances in genomics technologies that enable more high-throughput genetic
      testing, combined with research studies that identify additional EOC risk alleles
      will likely provide further opportunities to establish polygenic risk prediction
      approaches, based on combinations of rare high/moderate penetrance susceptibility
      genes and common, low penetrance susceptibility alleles. This article reviews the
      current literature describing the genetic and epidemiological components of
      ovarian cancer risk, and discusses both the opportunities and challenges in using
      this information for clinical risk prediction and prevention.

PMID- 29054569
TI  - Cause-specific mortality in endometrioid endometrial cancer patients with type 2
      diabetes using metformin or other types of antidiabetic medication.
AB  - AIM: To obtain further evidence of the association between metformin or other
      types of antidiabetic medication (ADM) and mortality from endometrial cancer (EC)
      and other causes of death in patients with endometrioid EC and type 2 diabetes
      (T2D). MATERIALS AND METHODS: A retrospective cohort of women with existing T2D
      and diagnosed with endometrioid EC from 1998 to 2011, obtained from a nationwide
      diabetes database (FinDM), were included in the study. Cumulative mortality from
      EC and that from other causes was described by using the Aalen-Johansen
      estimator. Cause-specific mortality rates were analyzed by using Cox models, and
      adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were
      estimated in relation to the use of different forms of ADM during the three-year
      period preceding EC diagnosis. RESULTS: From the FinDM cohort we identified 1215
      women diagnosed with endometrioid EC, of whom 19% were metformin users, 12% were
      users of other types of oral antidiabetic medication, 25% used other types of
      oral antidiabetic medication plus metformin, 26% used insulin and 14% had no
      antidiabetic medication. Mortality from EC was not found to be different in women
      using metformin (HR 0.89, 95% Cl 0.52-1.54) but mortality from other causes was
      lower (HR 0.52, 95% Cl 0.31-0.88) compared with women using other types of oral
      ADM. CONCLUSIONS: Our findings are inconclusive as to the possible effect of
      metformin on the prognosis of endometrioid EC in women with T2D. However, use of
      metformin may reduce mortality from other causes.

PMID- 29054571
TI  - Associations of DC-SIGN (CD209) promoter -336G/A polymorphism (rs4804803) with
      dengue infection: A systematic review and meta-analysis.
AB  - BACKGROUND AND AIM: Dengue virus entry into a host is associated with a cell
      surface protein, DC-SIGN (dendritic cell-specific intercellular adhesion molecule
      3 grabbing non-integrin). A common CD209-336G/A (rs4804803) polymorphism in DC
      SIGN may affect severity of dengue virus infection (DEN) and incidence of dengue
      fever (DF) or the more severe dengue hemorrhagic fever (DHF). However, the
      reported associations of these two outcomes and CD-209 have been inconsistent,
      which prompted a meta-analysis to obtain more precise estimates. METHODS: A
      literature search yielded seven case-control studies. We calculated pooled odds
      ratios (OR) and 95% confidence intervals using standard genetic models. Outlier
      treatment examined sources of potential heterogeneity. Subgroup analysis was
      performed for ethnicity and age. RESULTS: All significant outcomes for
      association indicating reduced risk were pegged at P=0.007-0.05. In the
      homozygous and recessive models, these were observed in the overall analysis (OR
      0.52-0.55), and subgroups of South/Central Americans (OR 0.30-0.32) and school
      age children (OR 0.44) in the DHF analysis as well as the codominant model among
      Asians in DF (OR 0.59). These significant outcomes are strengthened by their non
      heterogeneity (P>0.10) and robustness of the effects. Most pooled effects in DF
      and DEN were variable. CONCLUSIONS: The DC-SIGN -336G/A polymorphism
      significantly affects DHF and DF incidence with the effect more pronounced in
      certain analyzed patient subgroups.

PMID- 29054570
TI  - Estimated seroprevalence of Anaplasma spp. and spotted fever group Rickettsia
      exposure among herders and livestock in Mongolia.
AB  - BACKGROUND: To better understand the epidemiology of tick-borne disease in
      Mongolia, a comprehensive seroprevalence study was conducted investigating
      exposure to Anaplasma spp. and spotted fever group (SFG) Rickettsia spp. in
      nomadic herders and their livestock across three provinces from 2014 to 2015.
      METHODS: Blood was collected from 397 herders and 2370 livestock, including
      sheep, goats, cattle, horses and camels. Antibodies against Anaplasma spp. and
      SFG Rickettsia were determined by indirect immunofluorescence using commercially
      available slides coated with Anaplasma phagocytophilum and Rickettsia rickettsii
      antigens. Logistic regression was used to determine if the odds of previous
      exposure differed by gender, location, and species, with or without adjustment
      for age. To examine the association between seroprevalence and environmental
      variables we used ArcGIS to circumscribe the five major clusters where human and
      animal data were collected. RESULTS: Anaplasma spp. exposure was detected in
      37.3% (136/365) of humans and 47.3% (1120/2370) of livestock; SFG Rickettsia
      exposure was detected in 19.5% (73/374) humans and 20.4% (478/2342) livestock.
      Compared to the southern province (aimag) of Dornogovi, located in the Gobi
      Desert, humans were significantly more likely to be exposed to Anaplasma spp. and
      SFG Rickettsia in the northern provinces of Tov (OR=7.3, 95% CI: 3.5, 15.1;
      OR=3.3, 95% CI: 1.7, 7.5), and Selenge (OR=6.9, 95% CI: 3.4, 14.0; OR=2.2, 95%
      CI: 1.1, 4.8). CONCLUSION: The high seroprevalence of Anaplasma spp. and SFG
      Rickettsia in humans and livestock suggests that exposure to tick-borne pathogens
      may be common in herders and livestock in Mongolia, particularly in the more
      northern regions of the country. Until more is known about these pathogens in
      Mongolia, physicians and veterinarians in the countryside should consider testing
      for Anaplasma and SFG Rickettsia infections and treating clinically compatible
      cases, while public health authorities should expand surveillance efforts for
      these emerging infections.

PMID- 29054572
TI  - Chaotic genetic algorithm and Adaboost ensemble metamodeling approach for optimum
      resource planning in emergency departments.
AB  - Long length of stay and overcrowding in emergency departments (EDs) are two
      common problems in the healthcare industry. To decrease the average length of
      stay (ALOS) and tackle overcrowding, numerous resources, including the number of
      doctors, nurses and receptionists need to be adjusted, while a number of
      constraints are to be considered at the same time. In this study, an efficient
      method based on agent-based simulation, machine learning and the genetic
      algorithm (GA) is presented to determine optimum resource allocation in emergency
      departments. GA can effectively explore the entire domain of all 19 variables and
      identify the optimum resource allocation through evolution and mimicking the
      survival of the fittest concept. A chaotic mutation operator is used in this
      study to boost GA performance. A model of the system needs to be run several
      thousand times through the GA evolution process to evaluate each solution, hence
      the process is computationally expensive. To overcome this drawback, a robust
      metamodel is initially constructed based on an agent-based system simulation. The
      simulation exhibits ED performance with various resource allocations and trains
      the metamodel. The metamodel is created with an ensemble of the adaptive neuro
      fuzzy inference system (ANFIS), feedforward neural network (FFNN) and recurrent
      neural network (RNN) using the adaptive boosting (AdaBoost) ensemble algorithm.
      The proposed GA-based optimization approach is tested in a public ED, and it is
      shown to decrease the ALOS in this ED case study by 14%. Additionally, the
      proposed metamodel shows a 26.6% improvement compared to the average results of
      ANFIS, FFNN and RNN in terms of mean absolute percentage error (MAPE).

PMID- 29054573
TI  - Simulation as a surgical teaching model.
AB  - Teaching of surgery has been affected by many factors over the last years, such
      as the reduction of working hours, the optimization of the use of the operating
      room or patient safety. Traditional teaching methodology fails to reduce the
      impact of these factors on surgeons training. Simulation as a teaching model
      minimizes such impact, and is more effective than traditional teaching methods
      for integrating knowledge and clinical-surgical skills. Simulation complements
      clinical assistance with training, creating a safe learning environment where
      patient safety is not affected, and ethical or legal conflicts are avoided.
      Simulation uses learning methodologies that allow teaching individualization,
      adapting it to the learning needs of each student. It also allows training of all
      kinds of technical, cognitive or behavioural skills.

PMID- 29054574
TI  - Concepts, antecedents and consequences of ambulance ramping in the emergency
      department: A scoping review.
AB  - BACKGROUND: Patients arriving at the Emergency Department (ED) via ambulance can
      experience a delay in receiving definitive care. In Australia, this phenomenon is
      referred to as 'Ambulance Ramping', 'Patient Off Stretcher Time Delay' or
      'Offload Delay'. As a direct consequence of crowding, and in the context of a
      worldwide increase in ED and ambulance usage, hospital and ambulance service
      function is hampered. The aim of this review was to synthesize the literature
      with respect to the conceptualisation, meaning, antecedents and consequences of
      Ambulance Ramping. METHODS: This was a scoping review and synthesis of the
      literature. Six search terms were employed: emergency medical technician;
      paramedic; ambulance; hospital emergency services; delay; and ambulance ramping.
      Journal articles that discussed Ambulance Ramping (or similar terms), and were
      published in English between 1983 and March 2015 were included. PubMed and CINAHL
      Plus databases were searched, with secondary searches of reference lists and grey
      literature also undertaken. RESULTS: Thirteen papers were selected and inform
      this review. Several terms are used internationally to describe phenomena similar
      to Ambulance Ramping, where there is a delay in patient handover from paramedics
      to ED clinicians. Antecedents of Ambulance Ramping included reduction/limitation
      of ambulance diversion, patient acuity, the time of day, the day of the week,
      insufficient ED staff, insufficient ED beds, and high ED workload. Consequences
      of Ambulance Ramping include: further delays in patients' ability to receive
      definitive care and workforce stressors such as missed meal breaks, sick leave
      and staff attrition. CONCLUSION: While the existing research literature indicates
      that Ambulance Ramping is problematic, little is known about the patient's
      experience of Ambulance Ramping; this is required so that an enhanced
      understanding of its implications, including those for emergency nurses, can be
      identified.

PMID- 29054575
TI  - Emergency department presentations by older people for mental health or drug and
      alcohol conditions: A multicentre retrospective audit.
AB  - PURPOSE: Emergency department presentations by older people associated with
      mental health and drug and alcohol related conditions are increasing. However,
      the characteristics of presentations by older people in Australia are largely
      unknown. The aim of this research was to explore the characteristics of older
      people presenting with mental health and drug and alcohol conditions. PROCEDURES:
      We used a retrospective electronic medical record audit to explore all emergency
      department presentations by older people 65 years and over for mental health and
      drug and alcohol related conditions over a 12 month period. Data were described
      using descriptive statistics. FINIDNGS: There were 40,093 presentations; 2%
      (n=900) were related to mental health or drug and alcohol related conditions.
      Presentations were mainly associated with primary mental or medical symptoms. The
      majority were female (n=471; 53%). Predominate conditions were cognitive
      impairment (n=234; 26%) and affective disorders (n=233; 26.0%). Sixty-three
      percent of patients were admitted to a hospital ward. Over the study period 106
      patients (242 episodes of care) represented. PRINCIPLE CONCLUSIONS: Given the
      ageing population and increasing prevalence for mental health and drug and
      alcohol conditions, strategies are required to better recognise these conditions
      to reduce the burden on the health care system and improve health for older
      people.

PMID- 29054576
TI  - Skin infection in a renal transplant recipient.

PMID- 29054577
TI  - Annular plaque of beads distribution in the thorax in an elderly patient
      associated with poorly controlled diabetes mellitus.

PMID- 29054578
TI  - Tularemia in interepidemic period.

PMID- 29054579
TI  - Relevance of the CYP3A4*20 variant as a predictor of paclitaxel-induced
      neuropathy in the Spanish population.

PMID- 29054580
TI  - Bacteremia by Leptotrichia trevesanii. Case report.

PMID- 29054581
TI  - Mechanism of aggregation of UV-irradiated glycogen phosphorylase b at a low
      temperature in the presence of crowders and trimethylamine N-oxide.
AB  - To characterize the initial stages of protein aggregation, the kinetics of
      aggregation of UV-irradiated glycogen phosphorylase b (UV-Phb) was studied under
      conditions when the aggregation proceeded at a low rate (10 degrees C, 0.03M
      Hepes buffer, pH6.8, containing 0.1M NaCl). Aggregation of UV-Phb was induced by
      polyethylene glycol and Ficoll-70, acting as crowders, or a natural osmolyte
      trimethylamine N-oxide (TMAO). It has been shown that the initial rate of the
      stage of aggregate growth is proportional to the protein concentration squared,
      suggesting that the order of aggregation with respect to the protein is equal to
      two. It has been concluded that the aggregation mechanism of UV-Phb at 10 degrees
      C in the presence of crowders includes the nucleation stage and stages of protein
      aggregate growth (the basic aggregation pathway). The aggregation mechanism is
      complicated in the presence of TMAO, and the stage of aggregate-aggregate
      assembly induced by TMAO should be added to the basic aggregation pathway. It has
      been shown that the ability of TMAO at a low concentration (0.05M) to induce
      aggregation of UV-Phb is due to the decrease in the absolute value of zeta
      potential of the protein in the presence of TMAO.

PMID- 29054582
TI  - Characterization and functional analysis of a carboxylesterase gene associated
      with chlorpyrifos resistance in Nilaparvata lugens (Stal).
AB  - The widespread and extensive application of insecticides have promoted the
      development of resistance in the brown planthopper Nilaparvata lugens (Stal), one
      of the most important rice pests in Asia. To better understand the underlying
      molecular mechanisms of metabolic resistance to insecticides, a chlorpyrifos
      resistant (CR) strain of N. lugens was selected and its possible resistance
      mechanism was investigated. Synergistic tests using carboxylesterases (CarEs)
      inhibitor triphenyl phosphate (TPP) decreased the resistance of N. lugens to
      chlorpyrifos, and CarE activities could be induced by low concentrations of
      chlorpyrifos. Subsequently, a gene putatively encoding CarE, namely NlCarE,
      predominant in the midgut and ovary was isolated and characterized. The
      expression levels of NlCarE were detected and compared between the CR and a
      susceptible (SS) strain of N. lugens. Consistent with the increased CarE
      activity, this gene was overexpressed in the CR strain compared to the SS strain.
      The transcript levels of NlCarE were up-regulated by chlorpyrifos exposure,
      showing dose- and time-dependent expression patterns. Furthermore, RNA
      interference (RNAi)-mediated knockdown of NlCarE followed by insecticide
      application significantly increased the susceptibility of N. lugens to
      chlorpyrifos. These results demonstrate that NlCarE plays an important role in
      chlorpyrifos detoxification and its overexpression may be involved in
      chlorpyrifos resistance in N. lugens.

PMID- 29054584
TI  - [Abnormal hair].

PMID- 29054583
TI  - Dietary resveratrol increases mid-life fecundity of female Nothobranchius
      guentheri.
AB  - The decline of female reproductive function is an early phenotype of aging in
      humans, occurring only midway through the lifespan. Yet the number of women
      delaying pregnancy continues to rise in industrialized societies due to personal
      or socioeconomic circumstances, often resulting in subfertility or difficulty
      conceiving. There are few defined mechanisms associated with this etiology, and
      equally few effective therapies. To combat this problem, we used a novel emerging
      model, Nothobranchius guentheri, that recapitulates the age-associated spectrum
      of changes that adversely affect human fertility. We hypothesized that
      resveratrol (RSV), which activates SirT1 as an oxidative stress sensor and
      longevity assurance enzyme, would improve female fecundity in mid-life. RSV, a
      polyphenol found in grapes and red wine, has been touted as an anti-aging dietary
      supplement due to its ability to prolong both lifespan and health span. SirT1 is
      an NAD+ dependent histone deacetylase, whose activity is regulated by the
      nicotinamide to NAD+ salvage pathway, especially the rate-limiting enzyme NAMPT.
      We found that female N. guentheri fed 600MUgRSV/g food into mid-life (~20weeks),
      beginning at sexual maturity, showed increased embryo production compared to
      those on Control diet. Furthermore, the RSV-fed fish had significantly increased
      NAMPT. This suggests that dietary RSV has a positive effect on female fertility,
      and that it may become an effective therapy to regulate sirtuin activity and
      combat reproductive senescence.

PMID- 29054585
TI  - [Influence of epigenetic in Sjogren's syndrome].
AB  - Sjogren's syndrome (SS) is a systemic autoimmune epithelitis with a major female
      incidence, and characterized by a dry syndrome, impaired quality of life,
      visceral involvement, and lymphoma for the most aggressive cases. During this
      process, epithelial cells acquire the capacity to produce cytokines, chemokines,
      and autoantigens which can in turn be presented to the immune system.
      Consequently, this epithelitis is accompanied by lymphocytic infiltrations
      leading to the formation of pseudo-follicles in which self-reactive B lymphocytes
      are present. The recent integration of genomic and especially of epigenomic data,
      which make it possible to analyze the different cellular partners, opens new
      perspectives and allows to a better understanding of this complex and still
      incurable disease.

PMID- 29054586
TI  - Risk of metachronous ovarian cancer after ovarian conservation in young women
      with stage I cervical cancer: methodologic issues.

PMID- 29054587
TI  - Extrapyramidal signs in neurosarcoidosis versus multiple sclerosis: Is TNF alpha
      the link?
AB  - Specific inflammatory pathways and specifically Tumor Necrosis Factor alpha (TNF
      alpha) have been associated with the neurodegeneration in Parkinson's disease
      (PD). TNFalpha is also known to play an important role in the pathogenesis of
      sarcoidosis and TNF blockers can ameliorate the disease. In contrast, multiple
      sclerosis (MS) is clearly exacerbated by anti- TNF-alpha medications. We have
      therefore hypothesized that Parkinson-like disease would be more common in
      neurosarcoidosis (NS) compared to MS. The aim of this case-control study was
      therefore to assess the frequency of extrapyramidal signs in patients with NS
      compared to MS patients. In order to do so the medical records of NS patients and
      of age and gender matched MS patients were reviewed and data regarding the
      clinical features, ancillary tests performed, treatment, and outcome were
      documented. Patients were then examined in a uniform manner for the presence of
      extrapyramidal signs. We found that in the NS group 8 patients had minor signs,
      one had mild functional disability and 3 subjects had significant extrapyramidal
      signs compatible with the diagnosis of Parkinson's disease. All extrapyramidal
      signs found in 5 of the MS group were minor. The proportional severity of
      extrapyramidal signs was significantly higher (p=0.045, chi square test) in the
      NS group compared to the MS group. We conclude that the specificity of
      extrapyramidal to NS raises the intriguing question of whether specific
      inflammatory pathways involving TNF-alpha play a role in the pathogenesis of PD
      and therefore may be a therapeutic target.

PMID- 29054588
TI  - Titanium dioxide nanoparticles induce human eosinophil adhesion onto endothelial
      EA.hy926 cells via activation of phosphoinositide 3-kinase/Akt cell signalling
      pathway.
AB  - The use of nanoparticles (NPs) for developing new therapeutic strategies in a
      variety of diseases is gaining increasing attention. However, NPs could possess
      undesired effects, including pro-inflammatory activities. Despite the fact that
      several studies reported that NPs may induce or exacerbate eosinophilic
      inflammation in vivo in rodents, the information regarding the direct interaction
      between NPs and human eosinophils is lacking. In the present study, we test the
      possibility that NPs could alter the capacity of human eosinophils to adhere onto
      a cellular substratum. Using a panel of NPs, we found that several were able to
      increase the adhesion of human eosinophil onto endothelial EA.hy926 cells. Among
      them, TiO2 NPs were the most potent and we therefore pursue this study with these
      NPs. TiO2 NPs were found to increase the adhesion of eosinophils in a
      concentration dependent fashion. TiO2 NPs did not alter the cell surface
      expression of a panel of cellular adhesion molecules, but CD29. Indeed, a weak to
      moderate, but significant, decrease of CD29 was observed after 30min but returned
      to normal levels after 90min. TiO2 NPs were found to activate Akt, one important
      target of phosphoinositide 3-kinase (PI3K). However, despite the fact that cells
      were fully responsive to the cytokine GM-CSF activating both Akt and Erk-1/2,
      TiO2 NPs did not activate Erk-1/2. Using a pharmacological approach with the
      PI3K/Akt inhibitor, wortmannin, the ability of TiO2 NPs to activate Akt was
      drastically inhibited and, further, their capacity to increase adhesion of
      eosinophils was reversed. This study provides insights into the effects of NPs on
      the biology of human eosinophils indicating that as other agents, NPs, namely
      TiO2 NPs, can induce intracellular events associated with a cellular function,
      adhesion.

PMID- 29054589
TI  - Baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated
      patients in PROSPERO.
AB  - BACKGROUND: Patients included in clinical trials do not necessarily reflect the
      real-world population. OBJECTIVE: To understand the characteristics, including
      disease and comorbidity burden, of patients with asthma receiving omalizumab in a
      real-world setting. METHODS: The Prospective Observational Study to Evaluate
      Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) was a
      US-based, multicenter, single-arm, and prospective study. Patients (>=12 years of
      age) with allergic asthma initiating omalizumab treatment based on physician
      assessed need were included and followed for 12 months. Exacerbations, health
      care use, adverse events, and Asthma Control Test (ACT) scores were assessed
      monthly. Biomarkers (blood eosinophils, fractional exhaled nitric oxide, and
      periostin) were evaluated and patient-reported outcomes (Asthma Quality of Life
      Questionnaire for 12 Years and Older [AQLQ+12] and Work Productivity and Activity
      Impairment: Asthma questionnaire [WPAI:Asthma]) were completed at baseline and
      months 6 and 12. The Mini Rhinoconjunctivitis Quality of Life Questionnaire
      (MiniRQLQ) was completed at baseline and 12 months. RESULTS: Most of the 806
      enrollees (91.4%) were adults (mean age 47.3 years, SD 17.4), white (70.3%), and
      female (63.5%). Allergic comorbidity was frequently reported (84.2%), as were
      hypertension (35.5%) and depression (22.1%). In the 12 months before study entry,
      22.1% of patients reported at least 1 asthma-related hospitalization, 60.7%
      reported at least 2 exacerbations, and 83.3% reported ACT scores no higher than
      19 (uncontrolled asthma). Most patients had low biomarker levels based on
      prespecified cut-points. Baseline mean patient-reported outcome scores were 4.0
      (SD 1.4) for AQLQ+12, 2.7 (SD 1.4) for MiniRQLQ, and 47.7 (SD 28.9) for
      WPAI:Asthma percentage of activity impairment and 33.5 (SD 28.7) for percentage
      of overall work impairment. CONCLUSION: The population initiating omalizumab in
      PROSPERO reported poorly controlled asthma and a substantial disease burden.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01922037.

PMID- 29054590
TI  - Double fluorescent labelling of a bipolar epithelial cell in vitro: The outer
      hair cell.
AB  - BACKGROUND: Fluorescence membrane markers are efficient tools for visualizing the
      dynamics of membrane recycling processes in living cells. The outer hair cell
      (OHC) - a bipolar epithelial cell in the cochlea - possesses endocytic activity
      at both its apical and basal poles. The best visual overview of transcytosis in
      the OHC is achieved when the cell is isolated, so that both the apical and the
      basal poles are in the same focal plane to allow confocal imaging. Until now,
      fluorescent markers were applied to the extracellular environment of isolated
      OHCs without distinguishing the apical and basal poles. The drawback of that
      configuration is that apicobasal and basoapical vesicle traffic labelled at the
      opposite poles cannot be visualized independently because the same fluorescent
      marker has access to both poles. NEW METHOD: A double-barrel, capillary perfusion
      system was developed to independently stain either one pole or both the apical
      and the basal poles of isolated OHCs using different types of fluorescence
      membrane markers. RESULTS: Producing laminar fluid flow, the double-barrel
      perfusor allows investigation of the dynamics of apicobasal and basoapical
      vesicle traffic independently and/or simultaneously in the same OHC. COMPARISON
      WITH EXISTING METHOD: This method offers a unique option for investigating
      bidirectional vesicle traffic in bipolar epithelial cells, which is superior to
      other already established labelling techniques. CONCLUSIONS: The double-barrel
      perfusion system, suitable for selectively staining a longitudinal section of the
      plasma membrane of an isolated bipolar epithelial cell, opens new possibilities
      for investigating cell labelling and intracellular vesicle traffic.

PMID- 29054591
TI  - US alone trials presented during acquisition do not disrupt classical eyeblink
      conditioning: Empirical and computational findings.
AB  - Studies of partial reinforcement in eyeblink conditioning have typically shown
      slower learning of a CS-US association when paired CS-US trials are interleaved
      with CS-alone trials. However, recent work has shown that CS-US learning is not
      slowed by interleaved US-alone trials. This discrepancy is surprising since both
      partial reinforcement protocols reduce the total number of paired CS-US trials.
      Previously, Kimble et al. (1955) reported that inserting a block of US-alone
      trials during CS-US training did not disrupt eyeblink acquisition. Here, we
      sought to replicate and extend these findings by comparing interleaved vs.
      blocked US-alone trials during CS-US paired training. Ninety-seven undergraduates
      volunteered for this experiment for research credit. Participants received 60
      acquisition trials, consisting of either 100% CS-US paired trials, 50% US-alone
      trials intermixed with CS-US paired trials, or a block of 20 US-alone trials
      inserted between blocks of 20 CS-US trials. We also utilized a previously
      published computational model of hippocampal and cerebellar learning to test the
      effects of these US-alone protocols. Both empirical and computational results
      supported the finding that US-alone trials, either intermixed or inserted as a
      block of trials, do not disrupt acquisition of conditioned eyeblinks. Possible
      neural substrates of these US-alone effects are discussed.

PMID- 29054592
TI  - The impact of tissue Doppler index E/e' ratio on instantaneous wave-free ratio.
AB  - BACKGROUND: The instantaneous wave-free ratio (iFR) is a vasodilator-free,
      invasive pressure wire index of the functional severity of coronary stenosis and
      is calculated under resting conditions. In a recent study, iFR was found to be
      more closely linked to coronary flow reserve (CFR) than fractional flow reserve
      (FFR). E/e' is a surrogate marker of left ventricular (LV) filling pressure and
      LV diastolic dysfunction. Coronary resting flow was found to be increased in
      patients with elevated E/e', and higher coronary resting flow was associated with
      lower CFR. Higher baseline coronary flow induces a greater loss of translesional
      pressure and may affect iFR. However, no reports have examined the impact of E/e'
      on iFR. The purpose of this study was to assess the relationship between iFR and
      E/e' compared with FFR. METHODS AND RESULTS: We retrospectively examined 103
      consecutive patients (142 with stenosis) whose iFR, FFR, and E/e' were measured
      simultaneously. The mean age, LV mass index, and systolic blood pressure of
      patients with elevated E/e' were higher than those of patients with normal E/e'.
      Although no significant differences were observed in mean FFR values and %
      diameter stenosis, the mean iFR value in patients with elevated E/e' was
      significantly lower than that in patients with normal E/e'. The iFR was
      negatively correlated with E/e', while there was no correlation between FFR and
      E/e'. Multivariate analysis showed that E/e' and % diameter stenosis were
      independent determinants of iFR. CONCLUSION: E/e' ratio affects iFR values. Our
      results suggest that FFR mainly reflects the functional severity of the
      epicardial stenosis whereas iFR could potentially be influenced by not only
      epicardial stenosis but also other factors related to LV filling pressure or LV
      diastolic dysfunction. Further research is needed to understand the underlying
      mechanisms that influence the evaluation of iFR in patients with elevated E/e'.

PMID- 29054593
TI  - Association between the baseline peripheral blood monocyte counts, the size of
      spleen, and the response to cardiac resynchronization therapy.
AB  - BACKGROUND: Spleen reserves monocytes, which deploy to inflammatory sites.
      Monocytosis is known to be observed in chronic low-grade inflammatory state,
      including chronic heart failure (CHF). CHF also induces splenomegaly. We tested
      the hypotheses that the number of peripheral blood monocytes and size of spleen
      at baseline could be related to the response to cardiac resynchronization therapy
      (CRT). METHODS: From 2010, a total of 49 consecutive patients implanted with CRT
      device were evaluated at baseline and 6-8 months later. The size of spleen was
      evaluated at baseline by computed tomography. Blood monocyte counts (BMCs) were
      examined by blood test apparatus. RESULTS: Patients were categorized as
      responders (13 female, mean age 69.0+/-7.9 years, n=34) and nonresponders (2
      female, mean age 72.0+/-8.8 years, n=15) according to echocardiographic findings.
      In non-responders, spleen index was also greater in non-responders than in
      responders (4504+/-1338mm2 vs. 3240+/-1115mm2; mean+/-SE, p<0.01). Median
      baseline BMCs were significantly smaller in responders than non-responders (537+/
      211/MUl vs. 336+/-107/MUl, p<0.01). In addition, BMC is positively correlated
      with the spleen index (R2=0.179, p=0.02). Based on the receiver-operating
      characteristic curve, low BMC was set at <400/MUl. Kaplan-Meier survival analysis
      demonstrated that the low BMC patients had lower prevalence of new
      hospitalization due to HF progression (log rank 5.35, p=0.02). CONCLUSIONS: Our
      results demonstrated that BMC and the size of spleen might be important factors
      for response to CRT.

PMID- 29054594
TI  - What can be achieved with a single-payer NHI system: The case of Taiwan.
AB  - The United Nations has incorporated the noble goal of Universal Health Coverage
      (UHC) in its 2030 Agenda for Sustainable Development. Most nations have already
      embraced UHC as their goal. However, an intense policy debate has risen about
      which health system structure can best achieve UHC. Is a single-payer system more
      efficient, equitable and effective than a multiple-payer system for middle income
      countries? We argue that empirical evidence and in-depth analysis of single-payer
      and multiple-payer systems should inform this debate. First, we need a clear
      definition of single- and multiple-payer health systems that enables us to
      compare their differences and clarify the issues to be debated. Second, at least
      four key issues confront any nation that wishes to achieve UHC: (1) how to design
      an affordable comprehensive health benefit package for UHC and to finance it (2)
      how the health expenditure inflation rate can be managed to sustain UHC (3) how
      modern information technology can be used to enhance efficiency and quality of
      healthcare and (4) how to assure an adequate supply of high-quality services will
      be distributed equitably throughout a nation. This paper offers a definition of
      single- and multiple-payer and compares them. We then use Taiwan's National
      Health Insurance system to address the four key issues, and illuminate how its
      policies and operations led to Taiwan's successful UHC.

PMID- 29054595
TI  - The N-Acylethanolamine Acid Amidase Inhibitor ARN077 Suppresses Inflammation and
      Pruritus in a Mouse Model of Allergic Dermatitis.
AB  - N-acylethanolamine acid amidase (NAAA), a cysteine hydrolase highly expressed in
      macrophages and B lymphocytes, catalyzes the degradation of
      palmitoylethanolamide. Palmitoylethanolamide is an agonist of PPAR-alpha and an
      important regulator of pain and innate immunity. In this study, we investigated
      the properties of the NAAA inhibitor, ARN077, in a mouse model of allergic
      contact dermatitis. Acute topical applications of ARN077 attenuated key signs of
      DNFB-induced dermatitis in a dose-dependent manner. Moreover, ARN077 increased
      tissue palmitoylethanolamide content and normalized circulating levels of
      cytokines and immunoglobulin E. No such effect was seen in PPAR-alpha-deficient
      mice. Moreover, mice lacking NAAA failed to develop edema or scratching behavior
      after challenge with DNFB, confirming that this enzyme plays an important role in
      dermatitis. Consistent with this conclusion, subchronic applications of ARN077
      suppressed DNFB-induced inflammation when administered either before or after the
      DNFB challenge. The effects of subchronic ARN077 were dose dependent and
      comparable in size to those produced by the steroids clobetasol and
      dexamethasone. Unlike the latter, however, ARN077 did not cause skin atrophy. The
      results identify NAAA as a promising target for the development of effective and
      safe treatments for atopic dermatitis and other inflammatory disorders of the
      skin.

PMID- 29054596
TI  - Melanosome Distribution in Keratinocytes in Different Skin Types: Melanosome
      Clusters Are Not Degradative Organelles.
AB  - The melanosome pattern was characterized systematically in keratinocytes in situ
      in highly, moderately, and lightly pigmented human skin, classified according to
      the individual typological angle, a colorimetric measure of skin color phenotype.
      Electron microscopy of skin samples showed qualitatively and quantitatively that
      in highly pigmented skin, although melanosomes are mostly isolated and
      distributed throughout the entire epidermis, clusters are also observed in the
      basal layer. In moderately and lightly pigmented skin, melanosomes are
      concentrated in the first layer of the epidermis, isolated-but for most of them,
      grouped as clusters of melanocores delimited by a single membrane. Electron
      tomography resolving intracellular three-dimensional organization of organelles
      showed that clustered melanocores depict contacts with other cellular
      compartments, such as endoplasmic reticulum and mitochondria. Additionally,
      immunogold labelling showed that clusters of melanocores do not correspond to
      autophagosomes or melanophagosomes but that they present, similarly to
      melanosomes in melanocytes, features of nonacidic, nondegradative organelles.
      Overall, these observations suggest that melanocore clusters do not correspond to
      autophagic organelles but represent reservoirs or protective structures for
      melanosome integrity and function. These results open avenues for understanding
      the basis of skin pigmentation in different skin color phenotypes.

PMID- 29054597
TI  - STIM1, but not STIM2, Is the Calcium Sensor Critical for Sweat Secretion.

PMID- 29054598
TI  - Phlebotomus papatasi Yellow-Related and Apyrase Salivary Proteins Are Candidates
      for Vaccination against Human Cutaneous Leishmaniasis.
AB  - Nowadays, there is no available vaccine for human leishmaniasis. Animal
      experiments demonstrate that pre-exposure to sand fly saliva confers protection
      against leishmaniasis. Our preceding work in humans indicates that Phlebotomus
      papatasi saliva induces the production of IL-10 by CD8+ T lymphocytes. The
      neutralization of IL-10 enhanced the activation of a T-cell CD4+ population
      producing IFN-gamma. Herein, we used a biochemical and functional genomics
      approach to identify the sand fly salivary components that are responsible for
      the activation of the T helper type 1 immune response in humans, therefore
      constituting potential vaccine candidates against leishmaniasis. Fractionated P.
      papatasi salivary extracts were first tested on T lymphocytes of immune donors.
      We confirmed that the CD4+ lymphocytes proliferate and produce IFN-gamma in
      response to stimulation with the proteins of molecular weight >30 kDa. Peripheral
      blood mononuclear cells from immune donors were transfected with plasmids coding
      for the most abundant proteins from the P. papatasi salivary gland cDNA library.
      Our result showed that the "yellow related proteins," PPTSP42 and PPTSP44, and
      "apyrase," PPTSP36, are the proteins responsible for the aforementioned cellular
      immune response and IFN-gamma production. Strikingly, PPTSP44 triggered the
      highest level of lymphocyte proliferation and IFN-gamma production. Multiplex
      cytokine analysis confirmed the T helper type 1-polarized response induced by
      these proteins. Importantly, recombinant PPTSP44 validated the results observed
      with the DNA plasmid, further supporting that PPTSP44 constitutes a promising
      vaccine candidate against human leishmaniasis.

PMID- 29054599
TI  - Indoleamine 2,3-Dioxygenase Expression in Primary Cutaneous Melanoma Correlates
      with Breslow Thickness and Is of Significant Prognostic Value for Progression
      Free Survival.
AB  - The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of
      cancer development through its effects on cancer-associated inflammation. Recent
      studies report a significant improvement of the response rates in melanoma
      patients to PD-1 antibodies when IDO inhibitors were added to the regimen. Data
      on IDO expression in primary human melanomas are, however, incomplete and
      conflicting. Here, we show that the level of IDO expression in primary human
      melanoma cells significantly correlates with Breslow thickness (P = 0.003), the
      presence of tumor-infiltrating lymphocytes (P = 0.029), and the intensity of the
      peritumoral inflammatory infiltrate (P = 0.001). The expression of IDO in
      melanoma cells predicted independently of Breslow thickness and tumor stage (P =
      0.04). We further show that CD11c+ dendritic cells and CD68+ macrophages in the
      microenvironment of melanomas express IDO. The level of IDO expression in antigen
      presenting cells correlated positively to peritumoral inflammation (P = 0.001)
      but not to tumor-infiltrating lymphocytes. Significant negative correlation with
      progression-free survival was found for patients for whom antigen-presenting
      cells were very strongly IDO positive. These results suggest that IDO induction
      within melanoma cells may directly reflect tumor progression, whereas IDO in
      antigen-presenting cells may determine immune surveillance with impact on local
      and systemic tolerance.

PMID- 29054600
TI  - Microbe-Dependent Induction of IL-9 by CLA+ T Cells in Psoriasis and Relationship
      with IL-17A.
AB  - IL-9 is present in psoriatic lesions and is produced by lymphocytes. However, it
      is not known whether this cytokine is induced by relevant pathogenic triggers of
      psoriasis, such as Streptococcus pyogenes. Here we addressed the production of IL
      9 in response to various pathogens in a psoriatic ex vivo model. Extracts of S.
      pyogenes and Candida albicans triggered the production of IL-9 and also IL-17A
      and IFN-gamma. This induction was dependent on the interaction between CLA+ T
      cells and epidermal cells. Neutralization of IL-9 reduced S. pyogenes-induced IL
      17A production by CLA+ T cells but had no effect on IFN-gamma production. Also,
      IL-9 increased the survival of circulating psoriatic CLA+ T cells. Co-cultures
      from patients with guttate or plaque psoriasis with S. pyogenes produced similar
      amounts of IL-9. High cytokine responses in streptococcal-driven guttate patients
      paralleled peaks in Psoriasis Area Severity Index and anti-streptolysin O levels.
      Our results confirm that IL-9 promotes inflammation in psoriasis by up-regulating
      IL-17A production and support the clinical association of the immune response by
      streptococcal-sensitized CLA+ T cells with this cytokine, especially in guttate
      psoriasis.

PMID- 29054601
TI  - Disruption of TRPV3 Impairs Heat-Evoked Vasodilation and Thermoregulation: A
      Critical Role of CGRP.
AB  - Sensing environmental temperature is a key factor allowing individuals to
      maintain thermal homeostasis via thermoregulatory mechanisms, including changes
      to skin blood flow. Among transient receptor potential channels, transient
      receptor potential vanilloid 3 (TRPV3) is a heat-activated cation channel highly
      expressed in keratinocytes. However, the role of TRPV3 in triggering heat-evoked
      cutaneous vasodilation is unknown. Using a murine in vivo model of local acute
      environmental heat exposure in the skin, we show that TRPV3 is involved in the
      local thermoregulatory control of skin blood flow by initiating the release of
      calcitonin gene-related peptide and nitric oxide in response to local heating of
      the skin. In addition to their contribution in local heat-evoked vasodilation,
      TRPV3, calcitonin gene-related peptide, and nitric oxide also contribute to
      internal body temperature stability during passive whole-body heating. This study
      provides in vivo demonstration of the role of TRPV3 as a strong modulator of
      cutaneous vascular thermoregulatory mechanisms.

PMID- 29054602
TI  - STAT1 Gain-of-Function and Dominant Negative STAT3 Mutations Impair IL-17 and IL
      22 Immunity Associated with CMC.

PMID- 29054603
TI  - Risk of Serious Infection in Patients with Psoriasis Receiving Biologic
      Therapies: A Prospective Cohort Study from the British Association of
      Dermatologists Biologic Interventions Register (BADBIR).
AB  - Serious infection is a concern for patients with psoriasis receiving biologic
      therapies. We assessed the risk of serious infections for biologics used to treat
      psoriasis by comparison with a cohort receiving non-biologic systemic therapies
      in a propensity score-weighted Cox proportional hazards model using data from the
      British Association of Dermatologists Biologic Interventions Register. Overall,
      1,352; 3,271; and 994 participants were included in the etanercept, adalimumab,
      ustekinumab cohorts, respectively, and 3,421 participants were in the non
      biologic cohort. A total of 283 patients had a serious infection; the incidence
      rates with 95% confidence intervals (CI) per 1,000 person-years were as follows:
      non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9
      (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the
      risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10,
      95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab
      (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or
      methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR =
      1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk
      of serious infection should not be a key discriminator for patients and
      clinicians when choosing between non-biologic systemic therapies, etanercept,
      adalimumab, and ustekinumab for the treatment of psoriasis.

PMID- 29054604
TI  - Susceptibility Loci-Associated Cutaneous Squamous Cell Carcinoma Invasiveness.
AB  - Genome-wide association studies have identified genetic loci associated with
      cutaneous squamous cell carcinoma (cSCC) risk, but single-nucleotide polymorphism
      associations with cSCC invasiveness have not been investigated. We examined
      associations between cSCC invasiveness and 23 reported single-nucleotide
      polymorphisms among 67,833 non-Hispanic white subjects. Additionally, we
      performed a genome-wide scan and identified one SNP with significantly different
      frequencies in 5,724 subjects with at least one invasive tumor and 1,943 subjects
      with in situ tumors only. We then compared genotype frequencies among the
      invasive and in situ groups with those of 60,166 control subjects. The genome
      wide scan identified that the T allele in single-nucleotide polymorphism
      rs41269979 in the class II human leukocyte antigen region was more frequent in
      the invasive than the in situ group (P = 4.93 * 10-8). Single-nucleotide
      polymorphisms in five of the 23 previously associated loci showed odds ratio
      heterogeneity between the in situ and invasive groups: rs447510 in HLA-DQA1 (Phet
      = 2.93 * 10-3), rs12203592 in IRF4 (Phet = 3.94 * 10-4), rs1805007 in MC1R (Phet
      = 7.71 * 10-3), and two SNPs in DEF8 (rs4268748, Phet = 1.09 * 10-4 and
      rs8063761, Phet = 1.40 * 10-4). These findings may provide new insight into the
      genetic basis of cSCC invasiveness and may help identify individuals at higher
      risk for developing clinically aggressive cSCC.

PMID- 29054605
TI  - Increased Prevalence of Filaggrin Deficiency in 51 Patients with Recessive X
      Linked Ichthyosis Presenting for Dermatological Examination.

PMID- 29054606
TI  - Semaphorin 4D from CD15+ Granulocytes via ADAM10-Induced Cleavage Contributes to
      Antibody Production in Bullous Pemphigoid.
AB  - Autoreactive B-cell activation and antibody production are critical events for
      the development of bullous pemphigoid (BP). However, the mechanism that is
      involved in the modulation of B-cell activation and autoantibody generation has
      not been fully understood. Semaphorin 4D (Sema4D, or CD100) plays important roles
      in immune regulation related to B cells, but its implications in BP remain
      obscure. The aim of our study was to characterize Sema4D and the underlying
      mechanism contributing to the autoimmune features of BP. We found that soluble
      Sema4D (sSema4D) levels were elevated and correlated with disease severity and
      activity in serum and blister fluids from patients with BP. Additionally, Sema4D
      expressing cells accumulated in subepidermal blisters of BP lesions. In patient
      derived peripheral blood mononuclear cells, by promoting the differentiation of B
      cells into plasmablasts, sSema4D boosted anti-BP180/anti-BP230 antibody
      production in a time- and dose-dependent manner, which may be attributed to CD72
      mediated activation of Akt/NF-kappaB phosphorylated (p-)65/ERK cascades in B
      cells. We determined that a disintegrin and metalloproteinase 10 is a proteolytic
      enzyme for the cleavage of sSema4D from CD15+ granulocytes instead of T cells,
      which is probably responsible for the high concentration of sSema4D in BP blister
      fluid and serum. These findings suggest that Sema4D is a crucial participant in
      BP pathogenesis.

PMID- 29054607
TI  - Repigmentation of Human Vitiligo Skin by NBUVB Is Controlled by Transcription of
      GLI1 and Activation of the beta-Catenin Pathway in the Hair Follicle Bulge Stem
      Cells.
AB  - Vitiligo repigmentation is a complex process in which the melanocyte-depleted
      interfollicular epidermis is repopulated by melanocyte precursors from hair
      follicle bulge that proliferate, migrate, and differentiate into mature
      melanocytes on their way to the epidermis. The strongest stimulus for vitiligo
      repigmentation is narrow-band UVB (NBUVB), but how the hair follicle melanocyte
      precursors are activated by UV light has not been extensively studied. To better
      understand this process, we developed an application that combined laser capture
      microdissection and subsequent whole transcriptome RNA sequencing of hair
      follicle bulge melanocyte precursors and compared their gene signatures to that
      of regenerated mature epidermal melanocytes from NBUVB-treated vitiligo skin.
      Using this strategy, we found up-regulation of TNC, GJB6, and THBS1 in the hair
      follicle bulge melanocytes and of TYR in the epidermal melanocytes of the NBUVB
      treated vitiligo skin. We validated these results by quantitative real-time-PCR
      using NBUVB-treated vitiligo skin and untreated normal skin. We also identified
      that GLI1, a candidate stem cell-associated gene, is significantly up-regulated
      in the melanocytes captured from NBUVB-treated vitiligo bulge compared with
      untreated vitiligo bulge. These signals are potential key players in the
      activation of bulge melanocyte precursors during vitiligo repigmentation.

PMID- 29054608
TI  - A "sweet-spot" for fluid-induced oscillations in the conditioning of stem cell
      based engineered heart valve tissues.
AB  - Fluid-induced shear stresses are involved in the development of cardiovascular
      tissues. In a tissue engineering framework, this stimulus has also been
      considered as a mechanical regulator of stem cell differentiation. We recently
      demonstrated that the fluid-oscillating effect in combination with a
      physiologically-relevant shear stress magnitude contributes to the formation of
      stem cell-derived de novo heart valve tissues. However, the range of oscillations
      necessary to induce favorable gene expression and engineered tissue formation is
      unknown. In this study, we took a computational approach to establish a range of
      oscillatory shear stresses that may optimize in vitro valvular tissue growth.
      Taking a biomimetic approach, three physiologically-relevant flow waveforms from
      the human: (i) aorta, (ii) pulmonary artery and (iii) superior vena cava were
      utilized to simulate pulsatile flow conditions within a bioreactor that housed 3
      tissue specimens. Results were compared to non-physiological pulsatile flow
      (NPPF) and cyclic flexure-steady flow (Flex-Flow) conditions. The oscillatory
      shear index (OSI) was used to quantify the fluid-induced oscillations occurring
      on the specimen surfaces. The range of mean OSI under the physiological
      conditions investigated was found to be 0.18 <= OSI <= 0.23. On the other hand,
      NPPF and Flex-Flow environments yielded a mean OSI of 0.37 and 0.11 respectively,
      which were 46% higher and 45% lower than physiological conditions. Moreover, we
      subsequently conducted OSI-based human bone marrow stem cell (HBMSC) culture
      experiments which resulted in preferential valvular gene expression and phenotype
      (significant upregulation of BMP, KLF2A, CD31 and alpha-SMA using an OSI of 0.23
      in comparison to a lower OSI of 0.10 or a higher OSI of 0.38; p < .05). These
      findings suggest that a distinct range or a "sweet-spot" for physiological OSI
      exists in the mechanical conditioning of tissue engineered heart valves grown
      from stem cell sources. We conclude that in vitro heart valve matrix development
      could be further enhanced by simultaneous exposure of the engineered tissues to
      physiologically-relevant magnitudes of both fluid-induced oscillations and shear
      stresses.

PMID- 29054609
TI  - Estimating the L5S1 flexion/extension moment in symmetrical lifting using a
      simplified ambulatory measurement system.
AB  - Mechanical loading of the spine has been shown to be an important risk factor for
      the development of low-back pain. Inertial motion capture (IMC) systems might
      allow measuring lumbar moments in realistic working conditions, and thus support
      evaluation of measures to reduce mechanical loading. As the number of sensors
      limits applicability, the objective of this study was to investigate the effect
      of the number of sensors on estimates of L5S1 moments. Hand forces, ground
      reaction forces (GRF) and full-body kinematics were measured using a gold
      standard (GS) laboratory setup. In the ambulatory setup, hand forces were
      estimated based on the force plates measured GRF and body kinematics that were
      measured using (subsets of) an IMC system. Using top-down inverse dynamics, L5S1
      flexion/extension moments were calculated. RMSerrors (Nm) were lowest (16.6) with
      the full set of 17 sensors and increased to 20.5, 22 and 30.6, for 8, 6 and 4
      sensors. Absolute errors in peak moments (Nm) ranged from 17.7 to 16.4, 16.9 and
      49.3 Nm, for IMC setup's with 17, 8, 6 and 4 sensors, respectively. When
      horizontal GRF were neglected for 6 sensors, RMSerrors and peak moment errors
      decreased from 22 to 17.3 and from 16.9 to 13 Nm, respectively. In conclusion,
      while reasonable moment estimates can be obtained with 6 sensors, omitting the
      forearm sensors led to unacceptable errors. Furthermore, vertical GRF information
      is sufficient to estimate L5S1 moments in lifting.

PMID- 29054610
TI  - Inter- and intra-rater reliability of 3D kinematics during maximum mouth opening
      of asymptomatic subjects.
AB  - Previous studies evaluated 3D human jaw movements using kinematic analysis
      systems during mouth opening, but information on the reliability of such
      measurements is still scarce. The purpose of this study was to analyze within-
      and between-session reliabilities, inter-rater reliability, standard error of
      measurement (SEM), minimum detectable change (MDC) and consistency of agreement
      across raters and sessions of 3D kinematic variables during maximum mouth opening
      (MMO). Thirty-six asymptomatic subjects from both genders were evaluated on two
      different days, five to seven days apart. Subjects performed three MMO movements
      while kinematic data were collected. Intraclass correlation coefficient (ICC),
      SEM and MDC were calculated for all variables, and Bland-Altman plots were
      constructed. Jaw radius and width were the most reproducible variables (ICC>0.81)
      and demonstrated minor error. Incisor displacement during MMO and angular
      movements in the sagittal plane presented good reliability (ICC from 0.61 to 0.8)
      and small errors and, consequently, could be used in future studies with the same
      methodology and population. The variables with smaller amplitudes (condylar
      translations during mouth opening and closing and mandibular movements on the
      frontal and transversal planes) were less reliable (ICC<0.61) and presented
      larger SEM and MDC. Although ICC, SEM and MDC showed less between-session
      reproducibility than within-session and inter-rater, the limits of agreement were
      larger in inter-rater comparisons. In future studies care must be taken with
      variables collected on different days and with mandibular movements in the
      frontal and transversal planes.

PMID- 29054611
TI  - Maternal undernutrition during lactation alters nicotine reward and
      DOPAC/dopamine ratio in cerebral cortex in adolescent mice, but does not affect
      nicotine-induced nAChRs upregulation.
AB  - Early undernutrition causes long lasting alterations that affect the response to
      psychoactive drugs. Particularly, undernutrition during lactation affects the
      acute locomotor response to nicotine during adolescence, but the reward effect of
      continued exposure to nicotine remains unknown. The goal of this study was to
      investigate the effects of undernutrition during lactation on the nicotine
      susceptibility indexed via conditioned place preference (CPP), on dopamine
      content and turnover and on nicotine-induced nicotinic cholinergic receptor
      (nAChR) upregulation in the cerebral cortex, midbrain and hippocampus of
      adolescent mice. The impact of undernutrition and nicotine exposure on stress
      related hormones and leptin was also investigated. From postnatal day 2 (PN2) to
      weaning (PN21), dams were randomly assigned to one of the following groups:
      Control (C) - free access to standard laboratory diet (23% protein); Protein
      Restricted (PR) - free access to isoenergenetic diet (8% protein); Calorie
      Restricted (CR) - access to standard laboratory diet in restricted quantities
      (mean ingestion of PR). PR and CR groups showed less mass gain and less visceral
      fat mass. While C and CR were equally susceptible to nicotine-induced place
      preference conditioning, PR failed to show a conditioning pattern. In contrast,
      all groups presented a nicotine-evoked nAChR upregulation in the cerebral cortex.
      While dopamine and DOPAC levels did not differ between groups, the DOPAC/dopamine
      ratio was increased in CR animals. No differences in endocrine parameters were
      observed. Taken together, our results indicate that undernutrition during
      lactation programs for brain alterations later in life. Our data also suggest
      that early undernutrition does not affect the rewarding associative properties of
      nicotine at adolescence.

PMID- 29054612
TI  - Dihydropyrimidinase deficiency in four East Asian patients due to novel and rare
      DPYS mutations affecting protein structural integrity and catalytic activity.
AB  - Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation
      pathway and catalyzes the ring opening of 5,6-dihydrouracil and 5,6
      dihydrothymine. To date, only 31 genetically confirmed patients with a DHP
      deficiency have been reported and the clinical, biochemical and genetic spectrum
      of DHP deficient patients is, therefore, still largely unknown. Here, we show
      that 4 newly identified DHP deficient patients presented with strongly elevated
      levels of 5,6-dihydrouracil and 5,6-dihydrothymine in urine and a highly variable
      clinical presentation, ranging from asymptomatic to infantile spasm and reduced
      white matter and brain atrophy. Analysis of the DHP gene (DPYS) showed the
      presence of 8 variants including 4 novel/rare missense variants and one novel
      deletion. Functional analysis of recombinantly expressed DHP mutants carrying the
      p.M250I, p.H295R, p.Q334R, p.T418I and the p.R490H variant showed residual DHP
      activities of 2.0%, 9.8%, 9.7%, 64% and 0.3%, respectively. The crystal structure
      of human DHP indicated that all point mutations were likely to cause
      rearrangements of loops shaping the active site, primarily affecting substrate
      binding and stability of the enzyme. The observation that the identified
      mutations were more prevalent in East Asians and the Japanese population
      indicates that DHP deficiency may be more common than anticipated in these ethnic
      groups.

PMID- 29054613
TI  - The impact of nitrogen enrichment on grassland ecosystem stability depends on
      nitrogen addition level.
AB  - Increasing atmospheric nitrogen (N) deposition may affect plant biodiversity,
      subsequently altering ecosystem stability. While a few studies have explored how
      simulated N deposition affects community stability and its underlying mechanisms,
      the experimental levels of N addition used are usually higher than current and
      future N deposition rates. Thus, their results could produce highly uncertain
      predictions of ecosystem function, especially if the responses to N deposition
      are nonlinear. We conducted a manipulative experiment that simulated elevated
      atmospheric N deposition with several N addition levels to evaluate the effect of
      N deposition on ecosystem stability and its underlying mechanisms in a semiarid
      grassland in northern China. Here we show that N addition altered community
      diversity, reducing species richness, evenness, diversity and dominance. In
      addition, we found that N addition at current N deposition levels had no
      significant impact on community stability. In contrast, N addition at levels from
      4.6 to 13.8gNm-2yr-1 significantly decreased community stability, although
      community stability for the 13.8gNm-2yr-1 treatment was higher than that for the
      4.6gNm-2yr-1 treatment. These results indicate that the response of community
      stability to N enrichment is nonlinear. This nonlinear change in community
      stability was positively correlated with species asynchrony, species richness,
      and species diversity as well as the stability of dominant species and the
      stability of the grass functional group. Our data suggest a need to re-evaluate
      the mechanisms responsible for the effects of N deposition on natural ecosystem
      stability across multiple levels of N enrichment and that additional
      experimentation with gradients of N loads more similar to future atmospheric N
      deposition rates is needed.

PMID- 29054614
TI  - Accounting for dynamics of mean precipitation in drought projections: A case
      study of Brazil for the 2050 and 2070 periods.
AB  - Changes in drought around the globe are among the most daunting potential effects
      of climate change. However, changes in droughts are often not well distinguished
      from changes in aridity levels. As drought constitutes conditions of aridity, the
      projected declines in mean precipitation tend to override changes in drought.
      This results in projections of more dire changes in drought than ever. The
      overestimate of changes can be attributed to the use of 'static' normal
      precipitation in the derivation of drought events. The failure in distinguishing
      drought from aridity is a conceptual problem of concern, particularly to drought
      policymakers. Given that the key objective of drought policies is to determine
      drought conditions, which are rare and so protracted that they are beyond the
      scope of normal risk management, for interventions. The main objective of this
      Case Study of Brazil is to demonstrate the differences between projections of
      changes in drought based on 'static' and '30-year dynamic' precipitation normal
      conditions. First we demonstrate that the 'static' based projections suggest 4
      fold changes in the probability of drought-year occurrences against changes by
      the dynamic normal precipitation. The 'static-normal mean precipitation' based
      projections tend to be monotonically increasing in magnitude, and were arguably
      considered unrealistic. Based on the '30-year dynamic' normal precipitation
      conditions, the 13-member GCM ensemble median projection estimates of changes for
      2050 under rcp4.51 and rcp8.52 suggest: (i) Significant differences between
      changes associated with rcp4.5 and rcp8.5, and are more noticeable for droughts
      at long than short timescales in the 2070; (ii) Overall, the results demonstrate
      more realistic projections of changes in drought characteristics over Brazil than
      previous projections based on 'static' normal precipitation conditions. However,
      the uncertainty of response of droughts to climate change in CMIP5 simulations is
      still large, regardless of GCMs selection and translation processes undertaken.

PMID- 29054615
TI  - Where is the USA Corn Belt, and how is it changing?
AB  - The "Corn Belt" is a commonly used term, but often referenced as a vaguely
      defined region in the Midwest USA. A few key studies have delineated synoptic
      maps of the Corn Belt boundaries going back to the early 20th century, but a
      modern flexible and accessible framework for mapping the Corn Belt in space and
      time is needed. New tools provide reference maps for the Corn Belt in the 21st
      century and the ability to quantify space-time changes in corn cropping patterns.
      The Landuse and Agricultural Management Practices web-Service (LAMPS) was used to
      estimate the average corn (maize, Zea mays L.) area in each county of the
      contiguous 48 USA states for the years 2010-2016. LAMPS provides a modified areal
      Fraction of corn (Fc) used to map the Corn Belt at three intensity levels, for
      example. The resulting patterns illustrate a mostly contiguous Midwest Corn Belt
      surrounded by more scattered regions, including southern and eastern regions. We
      also mapped irrigated areas and temporal changes in Fc. Mapped patterns have the
      potential to help researchers study issues related to food, feed, biofuel, and
      water security.

PMID- 29054616
TI  - Green synthesized nanoclusters of ultra-small zero valent iron nanoparticles as a
      novel dye removing material.
AB  - Iron based nanoparticles have gained much attention in recent years due to their
      unique physicochemical properties especially in the environmental remediation
      practices. There has been an increasing demand for new sustainable techniques for
      production of these nanoparticles. In the present work, a novel iron
      nanostructure was successfully fabricated by a facile and green approach using
      the aqueous extract of Mediterranean cypress (Cupressus sempervirens). In fact,
      nanoclusters of highly reactive ultra-small (~1.5nm in diameter) iron
      nanoparticles were constructed. Diameters of iron nanoclusters were measured to
      be from 9 to 31nm with mean diameter of 19nm. Appearance of the characteristic X
      ray diffraction peak of zero valent iron at 2theta=43.5 degrees  indicates the
      great potential of Mediterranean cypress leaf extract for complete reduction of
      ferric ions. The presence of phytochemicals as organic capping agent was
      confirmed by IR radiation absorption at 1020cm-1 and 1623cm-1 corresponding to
      the presence of CO and carbonyl groups, respectively. The fabricated nanoclusters
      also showed a great potential for dye removal from aqueous solution in a time
      dependent manner. Decolourization efficiency was calculated to be 95% in a 6h
      process for methyl orange removal. The results of this study suggest the
      possibility of using iron nanoclusters for future pollutants removal applications
      from aqueous environments.

PMID- 29054617
TI  - Advantages and challenges associated with implementing an ecosystem services
      approach to ecological risk assessment for chemicals.
AB  - The ecosystem services (ES) approach is gaining broad interest in regulatory and
      policy arenas for use in landscape management and ecological risk assessment. It
      has the potential to bring greater ecological relevance to the setting of
      environmental protection goals and to the assessment of the ecological risk posed
      by chemicals. A workshop, organised under the auspices of the Society of
      Environmental Toxicology and Chemistry Europe, brought together scientific
      experts from European regulatory authorities, the chemical industry and academia
      to discuss and evaluate the challenges associated with implementing an ES
      approach to chemical ecological risk assessment (ERA). Clear advantages of using
      an ES approach in prospective and retrospective ERA were identified, including:
      making ERA spatially explicit and of relevance to management decisions (i.e.
      indicating what ES to protect and where); improving transparency in communicating
      risks and trade-offs; integrating across multiple stressors, scales, habitats and
      policies. A number of challenges were also identified including: the potential
      for increased complexity in assessments; greater data requirements; limitations
      in linking endpoints derived from current ecotoxicity tests to impacts on ES. In
      principle, the approach was applicable to all chemical sectors, but the scale of
      the challenge of applying an ES approach to general chemicals with widespread and
      dispersive uses leading to broad environmental exposure, was highlighted. There
      was agreement that ES-based risk assessment should be based on the magnitude of
      impact rather than on toxicity thresholds. The need for more bioassays/tests with
      functional endpoints was recognized, as was the role of modelling and the need
      for ecological production functions to link measurement endpoints to assessment
      endpoints. Finally, the value of developing environmental scenarios that can be
      combined with spatial information on exposure, ES delivery and service provider
      vulnerability was recognized.

PMID- 29054618
TI  - Relationships between soil organic matter pools and nitrous oxide emissions of
      agroecosystems in the Brazilian Cerrado.
AB  - In the Brazilian Cerrado, despite the increasing adoption of no-till systems,
      there are still extended areas under conventional soil management systems that
      reduce soil carbon (C) and nitrogen (N) stocks and increase the emissions of
      greenhouse gases, such as nitrous oxide (N2O). Conservation agroecosystems, such
      as no-till, have been proposed as a strategy to mitigate agriculture-induced
      climatic changes through reductions in N2O emissions. However, the relationship
      between organic matter and N2O emissions from soils under different
      agroecosystems is not yet clear. This study hypothesized that agroecosystems
      under no-till promote an accumulation of labile and stable SOM fractions along
      with a reduction of N2O emissions. This study evaluated the effects of crop
      rotation agroecosystems: i) on C and N pools and labile and stable SOM fractions;
      ii) on cumulative N2O emissions; and iii) on the relationships between SOM
      fractions and N2O emissions. The agricultural systems consisted of: (I) soybean
      followed by sorghum under no-tillage (NT1); (II) maize followed by pigeon pea
      under no-tillage (NT2); (III) soybean under conventional tillage followed by
      fallow soil (CT); (IV) and native Cerrado (CER). After CT for 18years, following
      the replacement of CER, the soil C stock in the 0-20cm layer was reduced by
      0.64tha-1year-1. The no-till systems were more efficient in accumulating labile
      and stable C fractions with values close to those observed under CER, and were
      directly related to lower soil N2O emissions. The cumulative pattern of N2O
      emissions was inverse to that of the following SOM fractions: microbial biomass
      carbon, permanganate-oxidizable carbon, particulate organic carbon, inert carbon,
      and humic substances. Based on principal component analysis, the CT was generally
      separated from the other land use systems. This separation was strongly
      influenced by the low C contents in the different SOM fractions and higher N2O
      emissions promoted by the CT.

PMID- 29054619
TI  - Effects of water-saving irrigation on the residues and risk of polycyclic
      aromatic hydrocarbon in paddy field.
AB  - The effects of different water-saving modes on PAHs residue and risk, field
      environment conditions and enzyme activities in paddy field were investigated in
      a field experiment plot in Laoyaba, Nanjing, China. Results showed that (1) water
      saving treatment affected greatly the SigmaPAHs in water and soil. The order of
      SigmaPAHs residue in surface water and groundwater in farmland is as follows: dry
      fields<water-saving paddy field<flooding irrigation paddy field. The SigmaPAHs in
      water during rice tillering stage were obviously higher than that in rice booting
      stage and milky stage, and the percentage of high-ring PAHs gradually reduced in
      water. (2) The residue of SigmaPAHs in soil in flooding irrigation paddy field
      (534.4+/-186.7ng/g) were more than water-saving irrigation (454.3+/-128.1ng/g)
      and dry cultivation paddy field (430.2+/-143.4ng/g), and the SigmaPAHs in dry
      field gradually decreased with the increase of water furrow number in farm. (3)
      When compared with flooding irrigation (337.87ng/g), water-saving (228.39ng/g)
      and dry cultivation (206.62ng/g) could obviously decrease the residue of
      SigmaPAHs in rice tissues (35%-55%), generally the concentration of SigmaPAHs in
      leaf>root>stem>rice grain. (4) Water-saving irrigation evidently decreased soil
      ecological risk (up to 55%-73%) and rice carcinogenic risk (up to 30%-45%) caused
      by PAHs compared with flooding irrigation. Water-saving irrigation could also
      reduce the Total Toxic Equivalency Concentration of PAHs in rice grain up to 50%
      relative to flooding irrigation. (5) The significant negative correlations were
      observed between the residual PAHs and the activities of laccase and dioxygenase
      (p<0.019), and the physical and chemical indexes (temperature, redox potential
      and dissolved oxygen of field, p<0.041). The changes of field environment
      conditions and enzyme activities induced by moisture control may be the main key
      factors affecting PAHs residue in water, soil and rice.

PMID- 29054620
TI  - Impact of treated wastewater for irrigation on soil microbial communities.
AB  - The use of treated wastewater (TWW) for irrigation has been suggested as an
      alternative to use of fresh water because of the increasing scarcity of fresh
      water in arid and semiarid regions of the world. However, significant barriers
      exist to widespread adoption due to some potential contaminants that may have
      adverse effects on soil quality and or public health. In this study, we
      investigated the abundance and diversity of bacterial communities and the
      presence of potential pathogenic bacterial sequences in TWW in comparison to
      synthetic fresh water (SFW) using pyrosequencing. The results were analyzed using
      UniFrac coupled with principal coordinate analysis (PCoA) to compare diversity
      and abundance of different bacterial groups in TWW irrigated soils to soils
      treated with SFW. Shannon diversity index values (H') suggest that microbial
      diversity was not significantly different (P<0.086) between soils with TWW and
      SFW. Pyrosequencing detected sequences of 17 bacterial phyla with Proteobacteria
      (32.1%) followed by Firmicutes (26.5%) and Actinobacteria (14.3%). Most of the
      sequences associated with nitrifying bacteria, nitrogen-fixing bacteria, carbon
      degraders, denitrifying bacteria, potential pathogens, and fecal indicator
      bacteria were more abundant in TWW than in SFW. Therefore, TWW effluent may
      contain bacterial that may be very active in many soil functions as well as some
      potential pathogens.

PMID- 29054621
TI  - Modelling regional cropping patterns under scenarios of climate and socio
      economic change in Hungary.
AB  - Impacts of socio-economic, political and climatic change on agricultural land
      systems are inherently uncertain. The role of regional and local-level actors is
      critical in developing effective policy responses that accommodate such
      uncertainty in a flexible and informed way across governance levels. This study
      identified potential regional challenges in arable land use systems, which may
      arise from climate and socio-economic change for two counties in western Hungary:
      Veszprem and Tolna. An empirically-grounded, agent-based model was developed from
      an extensive farmer household survey about local land use practices. The model
      was used to project future patterns of arable land use under four localised,
      stakeholder-driven scenarios of plausible future socio-economic and climate
      change. The results show strong differences in farmers' behaviour and current
      agricultural land use patterns between the two regions, highlighting the need to
      implement focused policy at the regional level. For instance, policy that
      encourages local food security may need to support improvements in the capacity
      of farmers to adapt to physical constraints in Veszprem and farmer access to
      social capital and environmental awareness in Tolna. It is further suggested that
      the two regions will experience different challenges to adaptation under possible
      future conditions (up to 2100). For example, Veszprem was projected to have
      increased fallow land under a scenario with high inequality, ineffective
      institutions and higher-end climate change, implying risks of land abandonment.
      By contrast, Tolna was projected to have a considerable decline in major cereals
      under a scenario assuming a de-globalising future with moderate climate change,
      inferring challenges to local food self-sufficiency. The study provides insight
      into how socio-economic and physical factors influence the selection of crop
      rotation plans by farmers in western Hungary and how farmer behaviour may affect
      future risks to agricultural land systems under environmental change.

PMID- 29054622
TI  - Effect of a strengthened ecological floating bed on the purification of urban
      landscape water supplied with reclaimed water.
AB  - A floating bed (FB) system vegetated with calamus, iris, lythrum, and Hydrocotyle
      vulgaris, and a strengthened FB (SFB) system with zeolite and sponge iron as
      fillers were simultaneously applied to purify urban landscape water in different
      zones. The urban landscape water, an artificial lake of approximately 326m2, was
      supplied with reclaimed water during a six-month experiment. Results indicated
      that the concentrations of nitrogen (N) and phosphorus (P) in the SFB zone (SFBZ)
      were significantly lower than those in the control zone (CZ) and the FB zone
      (FBZ) after six months of operation. The average removal efficiencies (AREs) in
      the SFBZ, FBZ and CZ were 89.98%, 77.39% and 56.37%, respectively, for ammonia
      nitrogen (NH4+-N); 92.49%, 79.55% and 47.85%, respectively, for phosphate (PO43-
      P). Meanwhile, the average concentration of Chlorophyll a and the algae density
      in SFBZ during the experiment were 12.54MUg/L and 1.31*104cells/mL, which were
      lower, obviously, than those in the FBZ and CZ. Moreover, the contribution rates
      analysis of nutrient removal exhibited that the plant absorption in the removal
      of N and P occupied 27.85% and 26.36%, whereas the filler adsorption occupied
      7.93% and 11.93%, respectively, in the SFB. Thus, the water quality of the
      artificial lake was improved greatly by the SFB which hybridized fillers and FB
      together. Finally, it was found that the AREs of NH4+-N and PO43--P in the SFBZ
      could reach 73.93% and 84.56%, approximately 1.39 and 1.41 times that of the FBZ
      during the winter. Therefore, the application of an SFB can keep a stable water
      quality in urban landscape water and avoid the lower removal rate of an FB at low
      temperature. In summary, the SFB could effectively improve the water quality of
      urban landscape water supplied with reclaimed water even in winter.

PMID- 29054623
TI  - From headwaters to estuary: Distribution and fate of halogenated flame retardants
      (HFRs) in a river basin near the largest HFR manufacturing base in China.
AB  - With the gradual phasing out of polybrominated diphenyl ethers (PBDEs), market
      demands for alternative halogenated flame retardants (HFRs) are increasing. The
      Laizhou Bay area is the biggest manufacturing base for brominated flame
      retardants (BFRs) in China, and the Xiaoqing River is the largest and most
      heavily contaminated river in this region. Water and sediment samples were
      collected from the headwaters to the estuary of the Xiaoqing River to investigate
      the distribution and fate of HFRs [i.e., PBDEs, alternative brominated flame
      retardants (aBFRs) and dechlorane plus (DPs). In the water samples, DPs was the
      most abundant flame retardant (median: 11.7ng/L), followed by
      decabromodiphenylethane (DBDPE) (5.92ng/L). In the sediment samples, DBDPE was
      the predominant flame retardant (39.5ng/g dw), followed by decabromodiphenyl
      ether (BDE 209) (2.81ng/g dw). The levels of DBDPE exceeded those of BDE 209 in
      most samples, indicating the overwhelming replacement of BDE 209 by DBDPE in this
      area. In the river section of this study, point source and atmospheric deposition
      followed by land runoff were the major factors influencing the distribution of
      HFRs, whereas in the estuary, riverine discharge, the estuarine maximum turbidity
      zone (MTZ), and hydrodynamic parameters played more important roles.
      Manufacturing is a significant source of contamination of the Xiaoqing River
      basin through atmospheric deposition and wastewater discharge.

PMID- 29054624
TI  - Erbium concentration anomaly as an indicator of nuclear activity: Focus on
      Natural waters in the Chernobyl exclusion zone.
AB  - This study focused on measurement of lanthanides in surface water (SW) and ground
      water (GW) samples from the Chernobyl Exclusion Zone. Results showed that the
      total lanthanide concentration in SW ranges from 500 to 1100ngL-1 and is about 10
      times lower than the GW concentration. The normalized patterns of lanthanide
      concentrations increase from lighter elements to heavier lanthanides.
      Concurrently, concentration anomalies of Ce, Eu, and Er are visible. The Er
      anomaly is the most noticeable and exceeds the theoretical calculation by about
      13 times. The Ce and Eu anomalies are likely related to the variety of oxidation
      states of these elements. Meanwhile, the cause of the Er anomaly is not
      completely clear, but is likely related to the Chernobyl Nuclear Power Plant
      accident, since increased concentrations correlate with the distribution of
      contamination in the zone. 137Cs activity measurements partially confirm this
      hypothesis. Simultaneously, there is a relationship between the positive Er
      anomaly and increase in 235U concentrations. However, there is no reliable
      information in the literature that indicates that Er was used in the Chernobyl
      Nuclear Power Plant before the reactor accident.

PMID- 29054625
TI  - Novel approach for removing brominated flame retardant from aquatic environments
      using Cu/Fe-based metal-organic frameworks: A case of hexabromocyclododecane
      (HBCD).
AB  - Cu and Fe based metal-organic frameworks (Cu-BTC and Fe-BTC) were synthesized via
      a simple solvothermal method and innovatively utilized to remove a typical
      nonionic brominated flame retardant, hexabromocyclododecane (HBCD), from aquatic
      environment. Results show that over 80% of HBCD was removed by Cu-BTC within 5h,
      which is 1.3 times higher than removal by Fe-BTC. Thermodynamic analysis confirms
      spontaneous adsorption of HBCD onto the metal-organic frameworks (MOFs).
      Furthermore, the Gibbs free energy of Cu-BTC (-9.11kJ/mol) is more negative than
      that of Fe-BTC (-5.04kJ/mol). Both adsorption isotherms of HBCD onto Cu-BTC and
      Fe-BTC followed the Langmuir model, indicating a typical monomolecular-layer
      adsorption mechanism. In addition, the water stability test of these MOFs shows
      that the collapse of the Cu-BTC crystal structure is significantly hindered in
      the aquatic environment due to adsorption of the hydrophobic HBCD. The proposed
      adsorption mechanism includes van der Waals and hydrophobic interactions. These
      findings demonstrate that Cu/Fe-BTC are promising adsorbents for the removal of
      hydrophobic organic pollutants from aquatic environments, and may further improve
      the understanding of MOF materials for environmental applications.

PMID- 29054626
TI  - Catalytic dehydrochlorination of lindane by nitrogen-containing multiwalled
      carbon nanotubes (N-MWCNTs).
AB  - This paper reports a nonreductive dechlorination pathway (dehydrochlorination) of
      lindane in the presence of N-MWCNTs (CNT-N1 and CNTN2) under environmentally
      relevant conditions. The enhanced catalytic dehydrochlorination at mild pH values
      (7.0-9.0) was mainly attributed to the Lewis base nature of nitrogen functional
      groups on the surface of N-MWCNTs, based on FT-IR spectra, X-ray photoelectron
      spectroscopy and CO2-TPD profile. Amine and pyridinic nitrogen species were
      inferred as the main basic sites that were responsible for the
      dehydrochlorination of lindane. The concentration of lindane was unchanged in
      homogenous alkaline aqueous solutions at pH7.0 and 8.0 within 6 d, and up to
      89.5% of lindane remained at pH9.0. In sharp contrast, the reaction rate constant
      (kobs) increased from 0.024 to 0.876 d-1 with the increasing pH from 7.0 to 9.0
      when CNT-N2 catalyst was used. All lindane was transformed in the presence of CNT
      N2 at pH9.0, leading to a much greater kobs as compared to that obtained in
      homogenous solution (0.876 vs 0.019 d-1). Even at neutral pH condition, the kobs
      obtained in the presence of CNT-N2 was higher than that observed in weakly
      alkaline solution (0.024 d-1 at pH7.0 vs 0.019 d-1 at pH9.0). gamma-1,3,4,5,6
      pentachlorocyclohexene and trichlorobenzene isomers were detected as the
      intermediate and final products, respectively. It might be inferred that amine
      and pyridinic nitrogen species could attack the hydrogen atom attached to the
      beta-carbon, and the dehydrochlorination of lindane followed a beta-elimination
      mechanism. This study provides an alternative dechlorination way for making
      lindane less toxic and better biodegradable under mild conditions, which is
      beneficial for complete mineralization of lindane when coupled with microbial
      degradation.

PMID- 29054628
TI  - Results of a paired catchment analysis of forest thinning in Turkey in relation
      to forest management options.
AB  - Adaptation to climate change has become a more serious concern as IPCC assessment
      reports estimate a rise of up to 2 degrees C in average global temperatures by
      the end of the century. Several recently published studies have underlined the
      importance of forest management in mitigating the impacts of climate change and
      in supporting the adaptation capacity of the ecosystem. This study focuses on the
      role of water-related forest services in this adaptation process. The effects of
      forestry practices on streamflow can best be determined by paired watershed
      analysis. The impact of two cutting treatments on runoff was analyzed by a paired
      experimental watershed study in the Belgrade Forest and the results were
      evaluated in relation to similar experiments conducted around the world. Forest
      thinning treatments at 11% and 18% were carried out in a mature oak-beech forest
      ecosystem over different time periods. Although the thinning increased the runoff
      statistically, the amount of surplus water remained <5% of the annual water
      yield. Evidently, the hydrologic response of the watersheds was low due to the
      reduced intensity of the timber harvest. Finally, the results were combined with
      those of global studies on thinning, clearcutting and species conversion with the
      aim of formulating management options for adaptation.

PMID- 29054627
TI  - Influence of diet in urinary levels of metals in a biomonitoring study of a child
      population of the Valencian region (Spain).
AB  - Pollution by trace elements and its possible effect on organisms has become a
      worldwide concern due to the increasing presence of trace elements in the
      environment and especially in the food chain. Exposure to chemicals has
      traditionally been measured using environmental samples, however, human
      biomonitoring brings a different perspective, in which all sources and exposure
      pathways are integrated. The objective of this paper is to discern the possible
      relationship between children's diet and the metals found in children urine. With
      this aim in mind, a total of 120 voluntaries participated in a diet survey
      carried out in a school-aged population (age 6-11) from the Valencian region. In
      addition, twenty trace elements were analysed in children urine (arsenic,
      antimony, barium, beryllium, caesium, cadmium, cobalt, copper, lead, manganese,
      mercury, molybdenum, nickel, platinum, selenium, thallium, thorium, uranium,
      vanadium and zinc). Results permitted to compare metal levels in urine with metal
      levels of other biomonitoring studies to conclude that values, including ours,
      were similar in most studies. On the other hand, children who ate more vegetables
      had the highest values in cadmium, copper, molybdenum, antimony, thallium,
      vanadium, and zinc, while those who ate more fish reached higher values in
      mercury. Finally, children who ate more cereals and baked products had higher
      values in total arsenic.

PMID- 29054629
TI  - Arsenic removal by Japanese oak wood biochar in aqueous solutions and well water:
      Investigating arsenic fate using integrated spectroscopic and microscopic
      techniques.
AB  - In this study, we examined the sorption of arsenite (As(III)) and arsenate
      (As(V)) to Japanese oak wood-derived biochar (OW-BC) in aqueous solutions, and
      determined its efficiency to remove As from As-contaminated well water. Results
      revealed that, among the four sorption isotherm models, Langmuir model showed the
      best fit to describe As(III) and As(V) sorption on OW-BC, with slightly greater
      sorption affinity for As(V) compared to As(III) (QL=3.89 and 3.16mgg-1; R2=0.91
      and 0.85, respectively). Sorption edge experiments indicated that the maximum As
      removal was 81% and 84% for As(III)- and As(V)-OW-BC systems at pH7 and 6,
      respectively, which decreased above these pH values (76-69% and 80-58%). Surface
      functional groups, notably OH, COOH, CO, CH3, were involved in As sequestration
      by OW-BC, suggesting the surface complexation/precipitation and/or electrostatic
      interaction of As on OW-BC surface. Arsenic K-edge X-ray absorption near edge
      structure (XANES) spectroscopy indicated that 36% of the added As(III) was
      partially oxidized to As(V) in the As(III) sorption experiment, and in As(V)
      sorption experiment, 48% of As(V) was, albeit incompletely, reduced to As(III) on
      OW-BC surface. Application of OW-BC to As-contaminated well water (As: 27-144MUgL
      1; n=10) displayed that 92 to 100% of As was depleted despite in the presence of
      co-occurring competing anions (e.g., SO42-, CO32-, PO43-). This study shows that
      OW-BC has a great potential to remove As from solution and drinking (well) water.
      Overall, the combination of macroscopic sorption data and integrated
      spectroscopic and microscopic techniques highlight that the fate of As on biochar
      involves complex redox transformation and association with surface functional
      moieties in aquatic systems, thereby providing crucial information required for
      implication of biochar in environmental remediation programs.

PMID- 29054630
TI  - Effects of land use and seasonality on stream water quality in a small tropical
      catchment: The headwater of Corrego Agua Limpa, Sao Paulo (Brazil).
AB  - Stream water quality is controlled by the interaction of natural and
      anthropogenic factors over a range of temporal and spatial scales. Among these
      anthropogenic factors, land cover changes at catchment scale can affect stream
      water quality. This work aims to evaluate the influence of land use and
      seasonality on stream water quality in a representative tropical headwater
      catchment named as Corrego Agua Limpa (Sao Paulo, Brasil), which is highly
      influenced by intensive agricultural activities and urban areas. Two systematic
      sampling approach campaigns were implemented with six sampling points along the
      stream of the headwater catchment to evaluate water quality during the rainy and
      dry seasons. Three replicates were collected at each sampling point in 2011.
      Electrical conductivity, nitrates, nitrites, sodium superoxide, Chemical Oxygen
      Demand (DQO), colour, turbidity, suspended solids, soluble solids and total
      solids were measured. Water quality parameters differed among sampling points,
      being lower at the headwater sampling point (0m above sea level), and then
      progressively higher until the last downstream sampling point (2500m above sea
      level). For the dry season, the mean discharge was 39.5ls-1 (from April to
      September) whereas 113.0ls-1 were averaged during the rainy season (from October
      to March). In addition, significant temporal and spatial differences were
      observed (P<0.05) for the fourteen parameters during the rainy and dry period.
      The study enhance significant relationships among land use and water quality and
      its temporal effect, showing seasonal differences between the land use and water
      quality connection, highlighting the importance of multiple spatial and temporal
      scales for understanding the impacts of human activities on catchment ecosystem
      services.

PMID- 29054631
TI  - "Green technology": Bio-stimulation by an electric field for textile reactive dye
      contaminated agricultural soil.
AB  - The aim of the study is to degrade pollutants as well as to increase the
      fertility of agricultural soil by starch enhancing electrokinetic (EKA) and
      electro-bio-stimulation (EBS) processes. Starch solution was used as an anolyte
      and voltage gradient was about 0.5V/cm. The influence of bacterial mediated
      process was evaluated in real contaminated farming soil followed by pilot scale
      experiment. The in-situ formation of beta-cyclodextrin from starch in the
      treatments had also influence on the significant removal of the pollutants from
      the farming soil. The conductivity of the soil was effectively reduced from
      15.5dS/m to 1.5dS/m which corroborates well with the agricultural norms. The bio
      stimulation was confirmed by the increase of the phosphorus content in the
      treated soil. Finally, phytotoxicity assays demonstrated the viability of the
      developed technique for soil remediation because plant germination percentage was
      higher in the treated soil in comparison to untreated soil.

PMID- 29054632
TI  - Nitrogen removal by thiosulfate-driven denitrification and plant uptake in
      enhanced floating treatment wetland.
AB  - This study investigated the potential of thiosulfate-driven autotrophic enhanced
      floating treatment wetland (AEFTW) in removing nitrogen from the secondary
      effluent at the relatively short hydraulic retention times and low S/N ratios.
      Simultaneous autotrophic and heterotrophic denitrification was observed in AEFTW.
      The peak TN removal rate (15.3gm-2d-1) exceeded most of the reported floating
      treatment wetlands. Based on the kinetic model results, low mean temperature
      coefficient and high k20 verified that the excellent performance in AEFTW
      diminished the microbial dependence on temperature. Nitrogen removal performance
      of enhanced floating treatment wetland (EFTW) and floating treatment wetland
      (FTW) were similar and highly sensitive to temperature. The interaction of sulfur
      transformation on the nitrogen, carbon uptake of plants was studied. Thiosulfate
      addition significantly raised sulfur content in the shoots and further enhanced
      the uptake of nitrogen and carbon, and increased the plant biomass at the same
      time. Higher composition of autotrophic and heterotrophic denitrifiers in AEFTW
      interpreted the occurrence of mixotrophic denitrification during summer.
      Thiosulfate induced mutual promotion of nitrogen removal by plant uptake and
      microbial denitrification in AEFTW.

PMID- 29054633
TI  - Climate change, tourism and historical grazing influence the distribution of
      Carex lachenalii Schkuhr - A rare arctic-alpine species in the Tatra Mts.
AB  - Mountain vegetation is highly specialized to harsh climatic conditions and
      therefore is sensitive to any change in environment. The rarest and most
      vulnerable plants occurring in alpine regions are expected to respond rapidly to
      environmental changes. An example of such a species is Carex lachenalii subsp.
      lachenalii Schkuhr, which occurs in Poland on only a few isolated sites in the
      Tatra Mts. The aim of this study was to assess changes in distribution of C.
      lachenalii in the Tatra Mts over the past 50-150years and the effects of climate
      change, tourism and historical grazing on the ecological niche of C. lachenalii.
      We focused on changes in the importance of functional diversity components in
      shaping plant species composition. Over the past 50-150years, the elevation of
      the average distribution of C. lachenalii shifted about 178m upward alongside a
      significant prolongation of the vegetative season by approximately 20days in the
      last 50-60years. Species composition of plots without C. lachenalii was
      characterized by competition between plants, whereas on plots with C. lachenalii
      habitat filtering was the most important component. Our results suggest that
      climate change was the main factor driving upward shift of C. lachenalii.
      Moderate trampling enhanced horizontal spread of this plant, whereas cessation of
      grazing grazing caused decline of C. lachenalii. The three environmental factors
      studied that determined shifts in distribution of C. lachenalii may also
      contribute to changes in distribution of other rare mountain plant species
      causing changes in ecosystem functioning.

PMID- 29054634
TI  - Personal care products in wild fish in two main Chinese rivers: Bioaccumulation
      potential and human health risks.
AB  - Personal care products (PCPs) are widely applied in our daily life, however,
      little is known about their occurrence in wild fish. We investigated the
      bioaccumulation and potential risks of 24 PCPs in muscle and liver tissues of
      wild fish collected from two large rivers of Pearl and Yangtze Rivers in China.
      The results showed the detection of a total of 13 PCPs including 9 biocides, 2
      synthetic musks and 2 benzotriazoles in at least one type of fish tissue from 12
      fish species. The compounds with high detection frequencies (>50%) in fish muscle
      or liver tissues were N,N-diethyl-3-methylbenzamide, carbendazim, climbazole,
      miconazole (MCZ), methylparaben, propylparaben, triclosan (TCS), tonalide,
      galaxolide (HHCB) and 5-methyl-1H-benzotriazole (5-TT). Among biocides, synthetic
      musks and benzotriazoles, TCS, HHCB and benzotriazole showed the maximum
      concentrations of 79.5ng/g wet weight (ww), 299ng/g ww and 3.14ng/g ww,
      respectively, in muscle tissue, while MCZ, HHCB and 5-TT showed the maximum
      concentrations of 432ng/g ww, 2619ng/g ww and 54.5ng/g ww, respectively, in liver
      tissue. The median values of logarithm of bioaccumulation factors (BAF) for the
      detected 13 PCPs were ranged 0.8-3.35 in muscle and 0.85-4.58 in liver. The log
      BAF values of the PCPs displayed good linear relationships with log Kow and log
      Dow (pH-dependent Kow). The health hazard assessment of 10 detected PCPs in the
      muscle indicated no appreciable risk to human via consumption of the wild fish.

PMID- 29054635
TI  - Emissions of volatile organic compounds (VOCs) from cooking and their speciation:
      A case study for Shanghai with implications for China.
AB  - Cooking emission is one of sources for ambient volatile organic compounds (VOCs),
      which is deleterious to air quality, climate and human health. These emissions
      are especially of great interest in large cities of East and Southeast Asia. We
      conducted a case study in which VOC emissions from kitchen extraction stacks have
      been sampled in total 57 times in the Megacity Shanghai. To obtain representative
      data, we sampled VOC emissions from kitchens, including restaurants of seven
      common cuisine types, canteens, and family kitchens. VOC species profiles and
      their chemical reactivities have been determined. The results showed that
      51.26%+/-23.87% of alkane and 24.33+/-11.69% of oxygenated VOCs (O-VOCs) dominate
      the VOC cooking emissions. Yet, the VOCs with the largest ozone formation
      potential (OFP) and secondary organic aerosol potential (SOAP) were from the
      alkene and aromatic categories, accounting for 6.8-97.0% and 73.8-98.0%,
      respectively. Barbequing has the most potential of harming people's heath due to
      its significant higher emissions of acetaldehyde, hexanal, and acrolein.
      Methodologies for calculating VOC emission factors (EF) for restaurants that take
      into account VOCs emitted per person (EFperson), per kitchen stove (EFkitchen
      stove) and per hour (EFhour) are developed and discussed. Methodologies for
      deriving VOC emission inventories (S) from restaurants are further defined and
      discussed based on two categories: cuisine types (Stype) and restaurant scales
      (Sscale). The range of Stype and Sscale are 4124.33-7818.04t/year and 1355.11
      2402.21t/year, respectively. We also found that Stype and Sscale for 100,000
      people are 17.07-32.36t/year and 5.61-9.95t/year, respectively. Based on
      Environmental Kuznets Curve, the annual total amount of VOCs emissions from
      catering industry in different provinces in China was estimated, which was
      5680.53t/year, 6122.43t/year, and 66,244.59t/year for Shangdong and Guangdong
      provinces and whole China, respectively. Large and medium-scaled restaurants
      should be paid more attention with respect to regulation of VOCs.

PMID- 29054636
TI  - Water chemistry of tundra lakes in the periglacial zone of the Bellsund Fiord
      (Svalbard) in the summer of 2013.
AB  - Climate changes observed in the Arctic (e.g. permafrost degradation, glacier
      retreat) may have significant influence on sensitive polar wetlands. The main
      objectives of this paper are defining chemical features of water within six small
      arctic lakes located in Bellsund (Svalbard) in the area of continuous permafrost
      occurrence. The unique environmental conditions of the study area offer an
      opportunity to observe phenomena influencing water chemistry, such as: chemical
      weathering, permafrost thawing, marine aerosols, atmospheric deposition and
      biological inputs. In the water samples collected during the summer 2013,
      detailed tundra lake water chemistry characteristics regarding ions, trace
      elements, pH and specific electrolytic conductivity (SEC25) analysis were
      determined. Moreover, water chemistry of the studied lakes was compared to the
      water samples from the Tyvjobekken Creek and precipitation water samples. As a
      final step of data analysis, Principal Component Analysis (PCA) was performed.
      Detailed chemical analysis allowed us to conclude what follows: (1) Ca2+, Mg2+,
      SO42-, Sr are of geogenic origin, (2) NO3- present in tundra lakes and the
      Tyvjobekken Creek water samples (ranging from 0.31 to 1.69mgL-1 and from 0.25 to
      1.58mgL-1 respectively) may be of mixed origin, i.e. from biological processes
      and permafrost thawing, (3) high contribution of non-sea-salt SO42->80% in
      majority of studied samples indicate considerable inflow of sulphate-rich air to
      the study area, (4) high content of chlorides in tundra lakes (range: 25.6-32.0%
      meqL-1) indicates marine aerosol influence, (5) PCA result shows that atmospheric
      transport may constitute a source of Mn, Co, Ni, Cu, Ga, Ba and Cd. However,
      further detailed inter-season and multi-seasonal study of tundra lakes in the
      Arctic are recommended. Especially in terms of detailed differentiation of
      sources influence (atmospheric transport vs. permafrost degradation).

PMID- 29054637
TI  - The burden of ambient temperature on years of life lost: A multi-community
      analysis in Hubei, China.
AB  - BACKGROUND: Compared with death rates, years of life lost (YLL) has been widely
      used as a more informative indicator to quantify the burden of premature death.
      In the context of global climate change, existing evidence linking ambient
      temperatures and YLL was very scarce across the globe. METHODS: Daily mortality
      and meteorological data during 2009-2012 were obtained from 12 communities across
      Hubei Province in central China. A two-stage approach was used for statistical
      analysis. At the first stage, a generalized linear regression combined with
      distributed lag non-linear model was applied to estimate community-specific
      temperature-YLL associations. A second-stage multivariable meta-analysis was then
      conducted to pool the community-specific estimates of temperature-related effects
      on YLL. RESULTS: A pooled J- or U-shaped association was observed between ambient
      temperature and YLL due to different mortality categories. Heat effects occurred
      immediately and only persisted for several days, whereas cold effects were
      delayed and much longer-lasting. At the provincial level, heat effect (per 1
      degrees C increase from 75th to 99th percentile of temperature) at lag 0-2days
      and cold effect (per 1 degrees C decrease from 25th to 1st percentile of
      temperature) at lag 0-21days was associated with an increase of 1.91% (95% CI:
      0.83, 3.00) and 5.09% (2.79, 7.40) in YLL due to non-accidental deaths,
      respectively. Much greater effect estimates of cold than heat were also observed
      for other mortality-specific YLLs (except for respiratory mortality). Heat
      effects on YLL were higher for males and the youth, while cold effects were
      greater for females and the elderly. Additionally, relatively stronger
      associations between heat, cold and YLL were consistently observed in low
      educated persons. CONCLUSIONS: This multi-community study strengthened the
      evidence that both cold and hot temperatures were associated with increased years
      of life lost. Our findings may have important implications for better
      understanding the burden of premature death related to temperature extremes.

PMID- 29054638
TI  - The persistent organochlorine pesticide endosulfan modulates multiple epigenetic
      regulators with oncogenic potential in MCF-7 cells.
AB  - Environmental cues and chemicals can potentially modulate the phenotypic
      expression of genome through alterations in the epigenetic mechanisms. Endosulfan
      is one of the extensively used organochlorine pesticides around the world which
      is known for its endocrine, neuro- and reproductive toxicity. This study was
      aimed to investigate the potential of alpha-endosulfan in modulation of multiple
      epigenetic enzymes in MCF-7 cells. The cells were treated with DMSO (control) or
      alpha-endosulfan (1 and 10MUM) and the expression of various epigenetic enzymes
      was assayed by real-time PCR and immunoblotting, in addition to their activity
      assays. The results shows alpha-endosulfan, at 1 and 10MUM concentration,
      significantly promoted viability of MCF-7 cells compared to untreated cells after
      24h. The expression of DNA methyltransferases (DNMTs) was upregulated while the
      global DNA methylation status was initially affected, but later recovered. Total
      intracellular histone deacetylase (HDAC) activity was found to be significantly
      increased which was correlated with upregulation of class I HDACs (HDAC 1 and 3)
      while no significant alteration in the other HDAC classes was observed. The
      expression and activity of arginine and lysine methylation enzymes, protein
      arginine methyltransferase 5 (PRMT5) and Enhancer of Zeste homolog 2 (EZH2),
      respectively, were also found to be modulated by alpha-endosulfan. We found
      increased expression of histones H3 and H4, trimethylated H3K27 (product of
      EZH2), symmetric dimethylation of H4R3 (product of PRMT5) and five different
      (unidentified) proteins whose arginine residues are symmetrically dimethylated
      (by increased level of PRMT5) were enhanced in response to 10MUM alpha-endosulfan
      after 24h exposure window. Moreover, overexpression of basal level of estrogen
      receptor alpha (ERalpha), suggests estrogenicity of alpha-endosulfan. In summary,
      our results shows modulatory impact of alpha-endosulfan on multiple cellular
      epigenetic regulators, known to possess oncogenic potential which might
      contribute to mechanistic insight of its action in future.

PMID- 29054639
TI  - Mobility of rare earth elements, yttrium and scandium from a phosphogypsum stack:
      Environmental and economic implications.
AB  - This paper investigates the mobility and fluxes of REE, Y and Sc under weathering
      conditions from an anomalously metal-rich phosphogypsum stack in SW Spain. The
      interactions of the phosphogypsum stack with rainfall and organic matter-rich
      solutions, simulating the weathering processes observed due to its location on
      salt-marshes, were simulated by leaching tests (e.g. EN 12457-2 and TCLP).
      Despite the high concentration of REE, Y and Sc contained in the phosphogypsum
      stack, their mobility during the leaching tests was very low; <0.66% and 1.8% of
      the total content of these elements were released during both tests. Chemical and
      mineralogical evidences suggest that phosphate minerals may act as sources of REE
      and Y in the phosphogypsum stack while fluoride minerals may act as sinks,
      controlling their mobility. REE fractionation processes were identified in the
      phosphogypsum stack; a depletion of LREE in the saturated zone was identified due
      probably to the dissolution of secondary LREE phosphates previously formed during
      apatite dissolution in the industrial process. Thus, the vadose zone of the stack
      would preserve the original REE signature of phosphate rocks. On the other hand,
      an enrichment of MREE in relation to HREE of edge outflows is observed due to the
      higher influence of estuarine waters on the leaching process of the phosphogypsum
      stack. Despite the low mobility of REE, Y and Sc in the phosphogypsum, around
      104kg/yr of REE and 40kg/yr of Y and Sc are released from the stack to the
      estuary, which may imply an environmental concern. The information obtained in
      this study could be used to optimize extraction methods aimed to recover REE, Y
      and Sc from phosphogypsum, mitigating the pollution to the environment.

PMID- 29054640
TI  - Apportioning source of erosion-induced organic matter in the hilly-gully region
      of loess plateau in China: Insight from lipid biomarker and isotopic signature
      analysis.
AB  - Understanding the dynamics of organic matter (OM) at global and local scales is
      one of the challenges in the environmental sciences and i.e. terrestrial
      biogeochemistry. The accurate identification of OM is an essential element to
      achieve this goal. In our study, a novel application for quantitatively
      apportioning sources of eroded sedimentary OM from an eco-geomorphologic
      perspective was shown successfully via a coupled molecular n-alkane biomarkers
      and stable isotopic signatures (13C and 15N) along with elemental compositions
      (TOC and TN) using a Bayesian mixing model (SIAR). Soil source samples were
      collected from different land use types (i.e., forests, grassland, cropland, and
      fallow) and gully, which were probably transported downstream along the steep
      terrain. Meanwhile, three soil profiles with a total of 90 sediment samples were
      also sampled in check dam. The results indicated that cropland was the main
      sedimentary OM source in this catchment, contributing 29.5%, whereas the forests,
      grassland, fallow and gully contributed 12.17%, 15.39%, 21.53% and 21.85%,
      respectively. Although the molecular biomarker as a tracer was not valid solely,
      the combined approaches of n-alkanes biomarker and bulk parameters were efficient
      complements in tracing OM source in a hilly-gully region on the Loess Plateau of
      China.

PMID- 29054641
TI  - Adsorption and correlations of selected aromatic compounds on a KOH-activated
      carbon with large surface area.
AB  - Knowledge of adsorption mechanism and behavior of organic compounds by KOH
      activated carbons (KOH-ACs) from wastewater is crucial to its environmental
      application in wastewater treatment as adsorbent. A superior adsorbent, KOH
      activated carbon (KOH-AC), with large surface area (3143m2/g), total pore volume
      of 2.03cm3/g, relatively low micropore fraction of 53.2%, and having adsorption
      capacities of organic compounds up to >1000mg/g, was prepared. It is an adsorbent
      significantly different with common ACs because the molecular sieving effect,
      widely observed for common ACs, is insignificant for KOH-AC. This difference
      could be attributed to the lower micropore fraction of KOH-AC than common ACs. A
      negative relationship of adsorption capacity of 25 aromatic compounds (including
      phenols, anilines, nitrobenzenes and polycyclic aromatic hydrocarbons) with
      chemical melting point was observed, suggesting that adsorption is dependent on
      the packing efficiency and stacking density of molecules on KOH-AC. A linear
      solvation energy relationships of adsorption affinity of 25 aromatic compounds
      with solute solvatochromic parameters was also observed, that can be used to
      quantify the contributions of pi-pi interaction, hydrogen-bonding interaction and
      hydrophobic effect to adsorption on KOH-AC. Combined with the reported results of
      adsorption of organic compounds on carbon nanotubes and biochars, it was also
      observed that external surface area of adsorbents is controlling the packing
      efficiency and stacking density of molecules on adsorbents and thus affecting
      adsorption capacity of organic compounds. Moreover, micropore surface area and
      the fraction of micropores are the adsorbent properties mainly affecting
      adsorption affinity of organic compounds. The observations and the developed
      correlations in this study would be helpful in the application of KOH-AC as
      superior adsorbent by enhancing the understanding of adsorption mechanisms of
      organic compounds on KOH-AC and by giving a method to predict the adsorption
      behaviors.

PMID- 29054642
TI  - Optical properties of algogenic organic matter within the growth period of
      Chlorella sp. and predicting their disinfection by-product formation.
AB  - Algogenic organic matter (AOM) in eutrophic waters is a well-known precursor to
      disinfection by-product (DBP) formation in drinking water. This purpose of this
      study is (i) to characterize the optical properties of AOM origins, including
      intra- (IOM) and extra-cellular organic matter (EOM), derived from Chlorella sp.
      growth as precursors to two major carbonaceous DBPs (C-DBPs), trihalomethanes
      (THMs) and haloacetic acids (HAAs) and (ii) to correlate these optical properties
      with THM and HAA formation potential (FP) in order to predict DBP formation. The
      results show that both EOM and IOM had low UV254 and UV280 absorbance during
      their entire growth phase. While IOM chiefly comprised of aromatic proteins and
      soluble microbial products-like substances (80% of average fluorescent intensity
      AFI), EOM spectra were rich in humic- and fulvic-like substances (60% AFI).
      However, its chemical nature likely differed from terrestrial humics. In DBPFP
      tests, IOM was a higher-yielding precursor of THMs and HAAs compared to EOM,
      regardless its growth status. Consequently, C-DBPFP of IOM was always higher than
      EOM during four growth phases. Results from DBP tests also showed insignificant
      variation of EOM-derived THMFP and HAAFP during the algal growth phase, while the
      algal growth status strongly influenced the yields of IOM-derived THMFP and
      HAAFP. From correlation analysis, our results showed no correlation between UV
      absorbance with THMFP and HAAFP. Conversely, the regional AFI showed a good
      correlation with HAAFP and C-DBPFP. Predicting models based on AFI for the
      formation of HAAs and C-DBPs consequently yielded great predictability for
      laboratory AOM-containing water samples, with a coefficient of determination
      R2=0.879, p<0.01 and R2=0.846, p<0.01. This study indicates a promising
      application of fluorescent spectra for predicting DBPs derived from algae-rich
      water sources.

PMID- 29054643
TI  - Polycyclic aromatic hydrocarbons in the urban atmosphere of Nepal: Distribution,
      sources, seasonal trends, and cancer risk.
AB  - Atmospheric polycyclic aromatic hydrocarbons (PAHs) in urban areas have always
      been a global concern, as these areas are considered to be the source region.
      Despite studies on the concentrations of PAHs in water, soils and sediments,
      knowledge of the distribution patterns, seasonality and sources of PAHs in urban
      areas of Nepal remains limited. In this study, polyurethane foam passive air
      samplers were used to measure gas-phase PAH concentrations over different land
      types in three major cities of Nepal-namely, Kathmandu (the capital) and Pokhara
      (both densely populated cities), and Hetauda (an agricultural city). The average
      concentrations of ?15PAHs in ng/m3 were 16.1+/-7.0 (6.4-28.6), 14.1+/-6.2 (6.8
      29.4) and 11.1+/-9.0 (4.1-38.0) in Kathmandu, Pokhara and Hetauda, respectively.
      Molecular diagnostic ratio analysis suggested that fossil fuel combustion was a
      common PAH source for all three cities. In addition to this, coal combustion in
      Kathmandu, vehicle emissions in Pokhara, and grass/wood combustion in Hetauda
      were also possible sources of PAHs. In terms of cancer risk from PAH inhalation,
      a religious site with intense incense burning, a brick production area where
      extensive coal combustion is common, and a market place with heavy traffic
      emission, were associated with a higher risk than other areas. There were no
      clear seasonal trends in atmospheric PAHs. The estimated cancer risk due to
      inhalation of gas-phase PAHs exceeded the USEPA standard at >90% of the sites.

PMID- 29054644
TI  - Legionella - A threat to groundwater: Pathogen transport in recharge basin.
AB  - This study elucidates the potential risk posed by Legionella during aquifer
      recharge practices. Experiments were conducted using pilot-scale column
      simulating infiltration of bacterial surrogate and pathogen, E. coli and
      Legionella pneumophila, under central Arizona recharge basin conditions. A column
      was packed with a loamy sand media collected from a recharge basin and was fitted
      with six sampling ports at soil depths of 15, 30, 60, 92, 122cm and acclimated
      for a month with tertiary treated wastewater. Transport of Legionella appeared to
      be delayed compared to E. coli. The breakthrough of E. coli and Legionella at
      122cm depth occurred at 3 and 24h, respectively. Slow transport of Legionella is
      consistent with its pleomorphic nature and variation in size and shape under low
      nutrient conditions. Legionella persisted for a longer time in the column, but at
      lower concentrations. Given the novel results of this study, the transport of
      Legionella into groundwater aquifers can occur through engineering recharge basin
      conditions creating a potential public health risk.

PMID- 29054645
TI  - How ecosystems change following invasion by Robinia pseudoacacia: Insights from
      soil chemical properties and soil microbial, nematode, microarthropod and plant
      communities.
AB  - Biological invasions are a global threat to biodiversity. Since the spread of
      invasive alien plants may have many impacts, an integrated approach, assessing
      effects across various ecosystem components, is needed for a correct
      understanding of the invasion process and its consequences. The nitrogen-fixing
      tree Robinia pseudoacacia (black locust) is a major invasive species worldwide
      and is used in forestry production. While its effects on plant communities and
      soils are well known, there have been few studies on soil fauna and microbes. We
      investigated the impacts of the tree on several ecosystem components, using a
      multi-trophic approach to combine evidence of soil chemical properties and soil
      microbial, nematode, microarthropod and plant communities. We sampled soil and
      vegetation in managed forests, comparing those dominated by black locust with
      native deciduous oak stands. We found qualitative and quantitative changes in all
      components analysed, such as the well-known soil nitrification and acidification
      in stands invaded by black locust. Bacterial richness was the only component
      favoured by the invasion. On the contrary, abundance and richness of
      microarthropods, richness of nematodes, and richness and diversity of plant
      communities decreased significantly in invaded stands. The invasion process
      caused a compositional shift in all studied biotic communities and in
      relationships between the different ecosystem components. We obtained clear
      insights into the effects of invasion of managed native forests by black locust.
      Our data confirms that the alien species transforms several ecosystem components,
      modifying the plant-soil community and affecting biodiversity at different
      levels. Correct management of this aggressive invader in temperate forests is
      urgently required.

PMID- 29054646
TI  - Heavy metal accumulation and health risk assessment in soil-wheat system under
      different nitrogen levels.
AB  - Heavy metal(loid)s (HMs) in organic fertilizer have become a primary source of
      HMs pollution of farmlands, which could cause deleterious health effects in
      people exposed through soil-plant systems via multi-pathways. This study
      investigated China's main grain production area (Henan Province) to evaluate the
      accumulation and transport characteristics of HMs (Cr, Mn, Ni, Cu, Zn, As, Cd and
      Pb) in a soil-wheat system and conduct a health risk assessment for wheat
      (Triticum aestivum) grain under different nitrogenous fertilizer treatments. The
      results indicated that the Cr, Cu, As and Cd contents in soil were 56.21-113.66,
      13.97-58.72, 5.79-22.62 and 0.04-0.23mg.kg-1, and the mean contents of Cr and As
      contents in wheat grains were 0.78+/-0.31 and 0.49+/-0.18mg.kg-1, respectively,
      which exceeded the corresponding standards. The bio-concentration factor and
      transfer factor were lowest in response to N-fertilization with N8-N15. Health
      risk assessment showed that the local population who ingested grain from culture
      condition of N15 experienced the lowest non-cancer and cancer risks. Among
      different population groups, HMs posed relatively higher non-cancer and cancer
      risks to children aged 0-5years. Furthermore, Cr and As exposure was the greatest
      contributor to Hazard Index (HI), accounting for 74.72-83.11%, while Cr exposure
      accounted for >90% of the total potential cancer risk. Concluding, this study
      indicated that, to protect human health, the current application of nitrogenous
      fertilizer should be controlled to an appropriate level.

PMID- 29054647
TI  - Pilot scale aided-phytoremediation of a co-contaminated soil.
AB  - A pilot scale experiment was conducted to investigate the aided-phytoextraction
      of metals and the aided-phytodegradation of petroleum hydrocarbons (PHC) in a co
      contaminated soil. First, this soil was amended with compost (10% w/w) and
      assembled into piles (Unp-10%C). Then, a phyto-cap of Medicago sativa L. either
      in monoculture (MS-10%C) or co-cropped with Helianthus annuus L. as companion
      planting (MSHA-10%C) was sown on the topsoil. Physico-chemical parameters and
      contaminants in the soil and its leachates were measured at the beginning and the
      end of the first growth season (after five months). In parallel, residual soil
      ecotoxicity was assessed using the plant species Lepidium sativum L. and the
      earthworm Eisenia fetida Savigny, 1826, while the leachate ecotoxicity was
      assessed using Lemna minor L. After 5months, PH C10-C40, PAH-L, PAH-M PAH-H, Pb
      and Cu concentrations in the MS-10%C soil were significantly reduced as compared
      to the Unp-10%C soil. Metal uptake by alfalfa was low but their translocation to
      shoots was high for Mn, Cr, Co and Zn (transfer factor (TF) >1), except for Cu
      and Pb. Alfalfa in monoculture reduced electrical conductivity, total organic C
      and Cu concentration in the leachate while pH and dissolved oxygen increased.
      Alfalfa co-planting with sunflower did not affect the extraction of inorganic
      contaminants from the soil, the PAH (M and H) degradation and was less efficient
      for PH C10-C40 and PAH-L as compared to alfalfa monoculture. The co-planting
      reduced shoot and root Pb concentrations. The residual soil ecotoxicity after
      5months showed a positive effect of co-planting on L. sativum shoot dry weight
      (DW) yield. However, high contaminant concentrations in soil and leachate still
      inhibited the L. sativum root DW yield, earthworm development, and L. minor
      growth rate.

PMID- 29054648
TI  - Distinct toxicity of silver nanoparticles and silver nitrate to Daphnia magna in
      M4 medium and surface water.
AB  - Toxicity of silver nanoparticles (AgNPs) has been studied in various culture
      media. However, these media notably differ from the natural aquatic system, thus
      the conclusions may be inapplicable for real environment condition. The toxicity
      and its underlying mechanism of AgNPs in surface waters warrant more
      investigations. This study investigated the acute toxicity, chronic toxicity,
      bioaccumulation, and alga-daphnia food chain transfer of citrate-coated AgNPs (C
      AgNPs) and Ag+ (from AgNO3) to D. magna in a culture medium (M4) and a surface
      water sample. Results show that the acute toxicity in the surface water was
      significantly lower than that in the M4 medium and the toxicity of Ag+ was
      greatly higher than that of C-AgNPs. The 48h median effect concentration (EC50)
      of C-AgNPs to D. magna in the M4 medium and the surface water was 110+/-9.3MUg/L
      and 270+/-26MUg/L, respectively, while that of Ag+ was 1.8+/-0.7MUg/L and 8.0+/
      0.6MUg/L, respectively. The released Ag+ contributed to but not dominated the
      acute toxicity of C-AgNPs. At the EC50 of C-AgNPs, the contribution of released
      Ag+ was 35.7% and 28.0% to the apparent nanotoxicity in the M4 medium and the
      surface water sample, respectively. The chronic toxicity of C-AgNPs and Ag+ was
      also lower in the surface water sample than in the M4 medium as indicated by the
      significantly higher survival of daphnia in the surface water during the 21d
      exposure. The daphnia took up less but depurated more Ag in the surface water
      than in the M4 medium, which could account for the lower toxicity in the surface
      water. Biological magnification of Ag through the alga-daphnia food chain was not
      observed. These findings will be helpful for assessing the environmental risk of
      AgNPs and understanding the mechanism of nanotoxcity.

PMID- 29054649
TI  - Response and recovery of fathead minnows (Pimephales promelas) following early
      life exposure to water and sediment found within agricultural runoff from the
      Elkhorn River, Nebraska, USA.
AB  - Agricultural runoff is a non-point source of chemical contaminants that are
      seasonally detected in surface water and sediments. Agrichemicals found within
      seasonal runoff can elicit endocrine disrupting effects in organisms as adults,
      juveniles and larvae. The objectives of this study were (1) to determine if
      exposure to water, sediment or the water-sediment combination collected from an
      agricultural runoff event was responsible for changes in endocrine-responsive
      gene expression and development in fathead minnow larvae, and (2) whether such
      early life exposure leads to adverse effects as adults. Larvae were exposed
      during the first month post-hatch to water and sediment collected from the
      Elkhorn River and then allowed to depurate in filtered water until reaching
      sexual maturity, exemplifying a best-case recovery scenario. Gas chromatography
      mass spectrometry (GC/MS) analysis of the water and sediment samples detected 12
      pesticides including atrazine, acetochlor, metolachlor and dimethenamid. In
      minnow larvae, exposure to river water upregulated androgen receptor gene
      expression whereas exposure to the sediment downregulated estrogen receptor alpha
      expression. Adult males previously exposed to both water and sediment were
      feminized through the induction of an ovipositor structure whereas no impacts
      were observed in other reproductive or sex characteristic endpoints for either
      sex based on exposure history. Results from this study indicate that both water
      and sediments found in agricultural runoff elicit responses from minnow larvae,
      and larvae can recover following early life exposure under a best-case scenario.

PMID- 29054650
TI  - Vitamin B12 effects on chlorinated methanes-degrading microcosms: Dual isotope
      and metabolically active microbial populations assessment.
AB  - Field-derived anoxic microcosms were used to characterize chloroform (CF) and
      carbon tetrachloride (CT) natural attenuation to compare it with biostimulation
      scenarios in which vitamin B12 was added (B12/pollutant ratio of 0.01 and 0.1) by
      means of by-products, carbon and chlorine compound-specific stable-isotope
      analysis, and the active microbial community through 16S rRNA MiSeq high
      throughput sequencing. Autoclaved slurry controls discarded abiotic degradation
      processes. B12 catalyzed CF and CT biodegradation without the accumulation of
      dichloromethane, carbon disulphide, or CF. The carbon isotopic fractionation
      value of CF (ECCF) with B12 was -14+/-40/00, and the value for chlorine (EClCF)
      was -2.4+/-0.40/00. The carbon isotopic fractionation values of CT (ECCT) were 
      16+/-6 with B12, and -13+/-20/00 without B12; and the chlorine isotopic
      fractionation values of CT (EClCT) were -6+/-3 and -4+/-20/00, respectively.
      Acidovorax, Ancylobacter, and Pseudomonas were the most metabolically active
      genera, whereas Dehalobacter and Desulfitobacterium were below 0.1% of relative
      abundance. The dual C-Cl element isotope slope
      (Lambda=Deltadelta13C/Deltadelta37Cl) for CF biodegradation (only detected with
      B12, 7+/-1) was similar to that reported for CF reduction by Fe(0) (8+/-2).
      Several reductive pathways might be competing in the tested CT scenarios, as
      evidenced by the lack of CF accumulation when B12 was added, which might be
      linked to a major activity of Pseudomonas stutzeri; by different chlorine
      apparent kinetic isotope effect values and Lambda which was statistically
      different with and without B12 (5+/-1 vs 6.1+/-0.5), respectively. Thus, positive
      B12 effects such as CT and CF degradation catalyst were quantified for the first
      time in isotopic terms, and confirmed with the major activity of species
      potentially capable of their degradation. Moreover, the indirect benefits of B12
      on the degradation of chlorinated ethenes were proved, creating a basis for
      remediation strategies in multi-contaminant polluted sites.

PMID- 29054651
TI  - Measuring soil sustainability via soil resilience.
AB  - Soils are the nexus of water, energy and food, which illustrates the need for a
      holistic approach in sustainable soil management. The present study therefore
      aimed at identifying a bioindicator for the evaluation of soil management
      sustainability in a cross-disciplinary approach between soil science and multi
      omics research. For this purpose we first discuss the remaining problems and
      challenges of evaluating sustainability and consequently suggest one measurable
      bioindicator for soil management sustainability. In this concept, we define soil
      sustainability as the maintenance of soil functional integrity. The potential to
      recover functional and structural integrity after a disturbance is generally
      defined as resilience. This potential is a product of the past and the present
      soil management, and at the same time prospect of possible soil responses to
      future disturbances. Additionally, it is correlated with the multiple soil
      functions and hence reflecting the multifunctionality of the soil system.
      Consequently, resilience can serve as a bioindicator for soil sustainability. The
      measurable part of soil resilience is the response diversity, calculated from the
      systematic contrasting of multi-omic markers for genetic potential and functional
      activity, and referred to as potential Maximum Ecological Performance (MEPpot) in
      this study. Calculating MEPpot will allow to determine the thresholds of
      resistance and resilience and potential tipping points for a regime shift towards
      irreversible or permanent unfavorable soil states for each individual soil
      considered. The calculation of such ecosystem thresholds is to our opinion the
      current global cross-disciplinary challenge.

PMID- 29054652
TI  - Filter feeders increase sedimentation of titanium dioxide: The case of zebra
      mussels.
AB  - Titanium dioxide particles (TiO2) are widely used to produce whitens (titanium
      white) and different class of nanomaterials (semiconductors, photo catalysts and
      nanotubes). Nanomaterials are excellent adsorbents and catalysts with a wide
      range of applications. However, these are reported to induce biological and
      genetic alterations among several invertebrate groups. Invasive species such as
      zebra mussels can be used as model organisms to study the behavior of particles
      and nanoparticles (NPs) due to their wide distribution; mussels have been
      extensively used for monitoring water pollution. In the present study, TiO2
      particles were dispersed and added to a Chlorella culture to emulate a natural
      scenario. To study the reaction of zebra mussels to different TiO2
      concentrations, they were fed with 0.35, 0.7 and 3.5 mgTiO2/L of the suspension
      for 3days and the titanium was measured in the water column, mussels and
      sediments with ICP-AES. Zebra mussels obtained from the Port of Quebec had up
      61.62mgTi/kg wet tissue at the time of capture. After 10days of depuration, they
      had from 0.23 to 16.28mgTi/kg wet tissue. Mussels accumulated TiO2 after 36h of
      exposition as a function of TiO2 concentration, but mussels did not present
      significant mortality due to TiO2 toxicity until concentrations higher than
      0.7ppm. A second set of experiments was run to understand the TiO2 pathway
      attached to microalgae vs free TiO2. Results indicated that mussels accumulated
      slightly more Ti when it was mixed with microalgae. However, the statistical
      difference was non- significant. A 100 times higher accumulation of Ti in
      sediments was identified when mussels are present. Thus, it was concluded that
      the sedimentation of TiO2 is enhanced by the zebra mussels' filtration activity.

PMID- 29054653
TI  - Importance of sediment organic matter to methane ebullition in a sub-tropical
      freshwater reservoir.
AB  - This paper summarises the results of an extensive field campaign which
      demonstrates that high sediment organic matter is the primary driver of methane
      ebullition in a sub-tropical, freshwater reservoir. Methane emissions from
      freshwater reservoirs represent an important global methane source. Whilst
      diffusive methane fluxes are commonly used for predicting total emissions, recent
      studies show that the under-reported ebullitive fluxes can vary by over three
      orders of magnitude within an individual system and have a greater relative
      contribution compared to diffusion. Key to predicting this variability in
      emission rates is to better understand the primary drivers of different emission
      pathways, and in particular ebullition. Zones of catchment derived organic
      material as well as elevated water column chlorophyll a concentration have been
      associated with increased rates of ebullition. Little Nerang Dam (LND), a
      subtropical freshwater reservoir in Queensland Australia, consistently
      experiences high rates of ebullition adjacent to major inflow arms that are both
      deposition zones of catchment organic material as well as areas with elevated
      water column chlorophyll a concentration. A year-long study of emission rates was
      undertaken on LND during which water column chlorophyll a concentration, bottom
      water temperature and sediment organic matter content were assessed for methane
      ebullition potential. This included a transect with high-spatial sampling (259
      sites) from the dam wall to the ebullition zones to explore the relationship
      between water column chlorophyll a concentration, sediment organic matter content
      and methane ebullition. These results showed that ebullition was associated with
      the large forest litter deposits adjacent to major inflow sites where sediment
      organic matter content was significantly higher compared with the main body of
      the reservoir.

PMID- 29054654
TI  - Assessing the potential impacts of a revised set of on-farm nutrient and sediment
      'basic' control measures for reducing agricultural diffuse pollution across
      England.
AB  - The need for improved abatement of agricultural diffuse water pollution
      represents cause for concern throughout the world. A critical aspect in the
      design of on-farm intervention programmes concerns the potential technical cost
      effectiveness of packages of control measures. The European Union (EU) Water
      Framework Directive (WFD) calls for Programmes of Measures (PoMs) to protect
      freshwater environments and these comprise 'basic' (mandatory) and
      'supplementary' (incentivised) options. Recent work has used measure review,
      elicitation of stakeholder attitudes and a process-based modelling framework to
      identify a new alternative set of 'basic' agricultural sector control measures
      for nutrient and sediment abatement across England. Following an initial
      scientific review of 708 measures, 90 were identified for further consideration
      at an industry workshop and 63 had industry support. Optimisation modelling was
      undertaken to identify a shortlist of measures using the Demonstration Test
      Catchments as sentinel agricultural landscapes. Optimisation selected 12 measures
      relevant to livestock or arable systems. Model simulations of 95% implementation
      of these 12 candidate 'basic' measures, in addition to business-as-usual,
      suggested reductions in the national agricultural nitrate load of 2.5%, whilst
      corresponding reductions in phosphorus and sediment were 11.9% and 5.6%,
      respectively. The total cost of applying the candidate 'basic' measures across
      the whole of England was estimated to be L450 million per annum, which is
      equivalent to L52 per hectare of agricultural land. This work contributed to a
      public consultation in 2016.

PMID- 29054655
TI  - Association of serum levels of perfluoroalkyl substances (PFASs) with the
      metabolic syndrome (MetS) in Chinese male adults: A cross-sectional study.
AB  - As extensively used chemicals in a variety of consumer products, perfluoroalkyl
      substances (PFASs) are ubiquitous and could bring significant risk to human
      health. However, the effect of PFASs on metabolic syndrome (MetS) is not fully
      understood. In 2015, a preliminary cross-sectional study was undertaken. A total
      of 148 male subjects including 81 affected by MetS and 67 non-MetS participants
      as the reference were recruited from Physical Examination Center affiliated to
      Capital Medical University, China. Serum levels of perfluorohexane sulfonic acid
      (PFHxS), perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) were
      significantly higher in the subjects with MetS. Logistic regression results
      showed that concentration of PFNA in serum was associated with 10.9-fold [95%
      confidence interval (CI), 2.00-59.1] increased risk of MetS. Moreover, increased
      serum PFNA concentrations were associated with high blood pressure [both for
      systolic and diastolic blood pressure (SBP and DBP); odds ratio (OR) 7.52 (95%CI,
      1.34-42.1) for SBP and 7.27 (95%CI, 1.17-45.1) for DBP], hypertriglyceridemia
      [13.2 (95%CI, 2.34-74.2)] and obesity [13.3 (95%CI, 2.38-74.4)], respectively.
      After adjustment by age in logistic regression models, serum levels of PFOA were
      associated with 29.4-fold (95%CI, 2.90-299.7) increased risk of MetS. Increased
      PFOA levels were also correlated with MetS [29.4 (95%CI, 2.9-299.7)], SBP [10.8
      (95%CI, 1.31-90.0)], hypertriglyceridemia [16.6 (95%CI, 1.92-147.1)], and obesity
      [46.7 (95%CI, 4.47-487.7)] with adjustment for age. This study suggests bodily
      retention of PFASs and its association with MetS. Further clinical and animal
      studies are warranted to clarify the putative causal relationship.

PMID- 29054656
TI  - Development and evaluation of diffusive gradients in thin films technique for
      measuring antibiotics in seawater.
AB  - As coastal waters in many regions of the world have been polluted by organic
      micro-pollutants such as antibiotics that can promote the development of
      resistance genes, it is of importance to monitor the levels of antibiotics in
      coastal waters. For this purpose, a reliable and robust sampling approach based
      on diffusive gradients in thin films (DGT) was developed in this study. The DGT
      measurement can provide a time weighted average concentration of pollutants. A
      binding material (resin XDA-1) with a high adsorption capacity for antibiotics,
      which can resist the pH and ionic strength of seawaters, was selected. The DGT
      sampler exhibited linear accumulation for 20 antibiotics during a 12h deployment.
      The antibiotic measurement by the sampler was not affected by pH in the range of
      7.3 to 8.9 and ionic strength in the range of 0.5 to 0.8M. After an 8-hour in
      situ DGT sampling, 10 antibiotics were detected in Dalian coastal seawaters with
      the concentrations ranging from 2.6 to 44.8ngL-1, which was comparable to the
      results measured by an active sampling method. This study can be a first attempt
      to construct DGT sampler for determining antibiotics in seawaters.

PMID- 29054657
TI  - Feed additives shift gut microbiota and enrich antibiotic resistance in swine
      gut.
AB  - Antibiotic resistance genes (ARGs) are emerging environmental contaminants posing
      a threat to public health. Antibiotics and metals are widely used as feed
      additives and could consequently affect ARGs in swine gut. In this study, high
      throughput quantitative polymerase chain reaction (HT-qPCR) based ARG chip and
      next-generation 16S rRNA gene amplicon sequencing data were analyzed using
      multiple statistical approaches to profile the antibiotic resistome and
      investigate its linkages to antibiotics and metals used as feed additives and to
      the microbial community composition in freshly collected swine manure samples
      from three large-scale Chinese pig farms. A total of 146 ARGs and up to 1.3*1010
      total ARG copies per gram of swine feces were detected. ARGs conferring
      resistance to aminoglycoside, macrolide-lincosamide-streptogramin B (MLSB) and
      tetracycline were dominant in pig gut. Total abundance of ARGs was positively
      correlated with in-feed antibiotics, microbial biomass and abundance of mobile
      genetic elements (MGEs) (P<0.05). A significant correlation between microbial
      communities and ARG profiles was observed by Procrustes analysis. Network
      analysis revealed that Bacteroidetes and Firmicutes were the most dominant phyla
      co-occurring with specific ARGs. Partial redundancy analysis indicated that the
      variance in ARG profiles could be primarily attributed to antibiotics and metals
      in feed (31.8%), gut microbial community composition (23.3%) and interaction
      between feed additives and community composition (16.5%). These results suggest
      that increased levels of in-feed additives could aggravate the enrichment of ARGs
      and MGEs in swine gut.

PMID- 29054658
TI  - Influence of organic matter, nutrients, and cyclodextrin on microbial and
      chemical herbicide and degradate dissipation in subsurface sediment slurries.
AB  - Pesticides leaching from soil to surface and groundwater are a global threat for
      drinking water safety, as no cleaning methods occur for groundwater environment.
      We examined whether peat, compost-peat-sand (CPS) mixture, NH4NO3, NH4NO3 with
      sodium citrate (Na-citrate), and the surfactant methyl-beta-cyclodextrin
      additions enhance atrazine, simazine, hexazinone, dichlobenil, and the degradate
      2,6-dichlorobenzamide (BAM) dissipations in sediment slurries under aerobic and
      anaerobic conditions, with sterilized controls. The vadose zone sediment cores
      were drilled from a depth of 11.3-14.6m in an herbicide-contaminated groundwater
      area. The peat and CPS enhanced chemical atrazine and simazine dissipation, and
      the peat enhanced chemical hexazinone dissipation, all oxygen-independently.
      Dichlobenil dissipated under all conditions, while BAM dissipation was fairly
      slow and half-lives could not be calculated. The chemical dissipation rates could
      be associated with the chemical structures and properties of the herbicides, and
      additive compositions, not with pH. Microbial atrazine degradation was only
      observed in the Pseudomonas sp. ADP amended slurries, although the sediment
      slurries were known to contain atrazine-degrading microorganisms. The
      bioavailability of atrazine in the water phase seemed to be limited, which could
      be due to complex formation with organic and inorganic colloids. Atrazine
      degradation by indigenous microbes could not be stimulated by the surfactant
      methyl-beta-cyclodextrin, or by the additives NH4NO3 and NH4NO3 with Na-citrate,
      although the nitrogen additives increased microbial growth.

PMID- 29054659
TI  - Enhanced transport of ferrihydrite colloid by chain-shaped humic acid colloid in
      saturated porous media.
AB  - Both humic acid and colloid particle size effectively regulate colloid transport.
      However, little is known about effect of particle size and configuration of humic
      acid colloid (HAcolloid) on enhanced-transport of ferrihydrite colloid
      (FHcolloid) in porous media. Co-transport of HAcolloid and FHcolloid at different
      pH was systematically investigated by monitoring breakthrough curves (BTCs) in
      saturated sand columns. The colloid transport model and the (X)DLVO theory were
      used to reveal the mechanism of HAcolloid-enhanced FHcolloid transport in the
      columns. Results showed that HAcolloid enhanced FHcolloid transport in neutral
      and alkaline conditions. In neutral conditions, small HAcolloid (F-HAcolloid)
      with chain-shaped structure enhanced FHcolloid transport more prominently than
      pristine granular HAcolloid. The chain-shaped F-HAcolloid caused osmotic
      repulsion and elastic-steric repulsion between colloids and sand, leading to
      enhanced transport. However, the granular HAcolloid readily occurred as
      deposition due to attachment and straining, which decreased the enhanced
      transport of FHcolloid. In alkaline conditions, both HAcolloid and F-HAcolloid
      were chain-shaped, with longer chains of HAcolloid than F-HAcolloid. Ferrihydrite
      colloid transport was enhanced by HAcolloid more significantly than F-HAcolloid
      due to stronger repulsion between mixed HAcolloid-FHcolloid and sand. It
      suggested that regulation of particle size and morphology of HAcolloid would
      enhance FHcolloid transport and further help in understanding FHcolloid
      facilitated contaminants transport in porous media.

PMID- 29054660
TI  - Estimation of intake and uptake of bisphenols and triclosan from personal care
      products by dermal contact.
AB  - Increasing concern has been raised in respect of exposure to bisphenols and
      triclosan (TCS) due to their widespread use. However, little is known about their
      occurrence in personal care products (PCPs) or, particularly, their dermal uptake
      following daily application. It is therefore necessary to evaluate the human
      health risk of bisphenols and TCS via dermal absorption. In this study, 150 PCPs,
      covering 11 different categories, were collected in China. The concentrations of
      seven bisphenol analogues and TCS were measured, and the associated human health
      risks by dermal contact were estimated. High detection frequencies of TCS (46.7%)
      and bisphenol AF (38.7%) were found in the PCPs. The highest mean concentration
      of Sigma7BPs (sum concentration of all seven bisphenols) was 77.8ngg-1 found in
      masks, and the highest mean concentration of TCS was 86.7ngg-1 in hand
      sanitizers. The bisphenol composition profiles varied among different categories.
      Bisphenol A and bisphenol F generally showed higher concentrations. Combining the
      concentrations of the target substances with the daily usage quantities of PCPs
      and other parameters, the total estimated dermal intakes and uptakes of Sigma7BPs
      and TCS were calculated. The results showed that the former (12.1 and 1.06ng.kg
      1bwday-1) were markedly higher than the latter (1.21 and 9.58*10-2ng.kg-1bwday
      1), which included dermal absorption rates of the chemicals in the estimation.
      Although diet is the main source, and oral ingestion is the main route, for human
      BPA exposure, the results of the estimated dermal uptakes of BPA in the present
      study combined with those from a European study show that dermal contact is the
      main route with thermal paper being the main contributor when both unconjugated
      and conjugated BPA in the human body are considered. The present study also
      showed that exposure to BPA in PCPs following dermal contact should not be
      ignored.

PMID- 29054661
TI  - Coordinated role of soluble and cell wall bound phenols is a key feature of the
      metabolic adjustment in a mining woody fleabane (Dittrichia viscosa L.)
      population under semi-arid conditions.
AB  - Environmental contamination by hazardous heavy metals/metalloids (metal(loid)s)
      is growing worldwide. To restrict the migration of toxic contaminants, the
      establishment of a self-sustainable plant cover is required. Plant growth in
      multi-polluted soils is a challenging issue not only by metal(loid) toxicities,
      but also by the co-occurrence of other stressors. Dittrichia viscosa is a pioneer
      Mediterranean species able to thrive in metal(loid)-enriched tailings in semi
      arid areas. The aim of the present work was to examine the metabolic adjustments
      involved in the acclimation responses of this plant to conditions prevailing in
      mine-tailings during Mediterranean spring and summer. For this purpose, fully
      expanded leaves, and rhizosphere soil of both mining and non-mining populations
      of D. viscosa grown spontaneously in south-eastern Spain were sampled in two
      consecutive years. Quantitative analysis of >50 biochemical, physiological and
      edaphic parameters were performed, including nutrient status, metal(loid)
      contents, leaf redox components, primary and secondary metabolites, salicylic
      acid levels, and soil physicochemical properties. Results showed that mining
      plants exhibited high foliar Zn/Pb co-accumulation capacity, without
      substantially affecting their photosynthetic metabolism or nutritional status
      even in the driest summer period. The comparison of the antioxidative/oxidative
      profile between mining and non-mining D. viscosa populations revealed no major
      seasonal changes in the content of primary antioxidants (ascorbate and GSH), or
      in the levels of ROS. Multivariate analysis showed that phenylalanine ammonia
      lyase (PAL) and peroxidase (PRX) activities and soluble and cell wall-bound
      phenols were potential biomarkers for discriminating between both populations.
      During the dry season, a marked enhancement in the activity of both PAL and
      soluble PRX resulted in both a drop in the accumulation of soluble phenols and an
      increase of the strong metal chelator caffeic acid in the cell-wall fraction,
      supporting the view that the plasticity of phenylpropanoid metabolism provide an
      effective way to counteract the effects of stress combinations.

PMID- 29054662
TI  - Assessing the ecological effects of water stress and pollution in a temporary
      river - Implications for water management.
AB  - Temporary rivers are dynamic and complex ecosystems that are widespread in arid
      and semi-arid regions, such as the Mediterranean. Biotic communities adapted in
      their intermittent nature could withstand recurrent drought events. However,
      anthropogenic disturbances in the form of water stress and chemical pollution
      challenge biota with unpredictable outcomes, especially in view of climate
      change. In this study we assess the response of the biotic community of a
      temporary river to environmental stressors, focusing on water stress and
      pollution. Towards this aim, several metrics of four biotic groups (diatoms,
      macrophytes, macroinvertebrates and fish) were applied. All biotic groups
      responded to a pollution gradient mainly driven by land use, distinct functional
      groups of all biota responded to water stress (a response related to the
      rheophilic nature of the species and their resistance to shear stress), while the
      combined effects of water stress and pollution were apparent in fish. Biotic
      groups presented a differential temporal response to water stress, where diatom
      temporal assemblage patterns were explained by water stress variables of short
      time response (15days), while the responses of the other biota were associated to
      longer time periods. There were two time periods of fish response, a short
      (15days) and a long-time response (60-75days). When considering management
      decisions, our results indicate that, given the known response of river biota to
      pollution, biomonitoring of temporary rivers should also involve metrics that can
      be utilized as early warnings of water stress.

PMID- 29054663
TI  - Characterization of bacterial diversity in contaminated groundwater using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Groundwater is a major source for drinking water in the United States, and
      therefore, its quality and quantity is of extreme importance. One major concern
      that has emerged is the possible contamination of groundwater due to the
      unconventional oil and gas extraction activities. As such, the impacts of
      exogenous contaminants on microbial ecology is an area to be explored to
      understand what are the chemical and physical conditions that allow the
      proliferation of pathogenic bacteria and to find alternatives for water treatment
      by identifying organic-degrading bacteria. In this work, we assess the interplay
      between groundwater quality and the microbiome in contaminated groundwaters rich
      in hydrocarbon gases, volatile organic and inorganic compounds, and various
      metals. Opportunistic pathogenic bacteria, such as Aeromonas hydrophila, Bacillus
      cereus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia, were
      identified, increasing the risk for consumption of and exposure to these
      contaminated groundwaters. Additionally, antimicrobial tests revealed that many
      of the identified bacteria were resistant to different antibiotics. The MALDI-TOF
      MS results were successfully confirmed with 16S rRNA gene sequencing, proving the
      accuracy of this high-throughput method. Collectively, these data provide a
      seminal understanding of the microbial populations in contaminated groundwater
      overlying anthropogenic activities like unconventional oil and gas development.

PMID- 29054664
TI  - Characterization of nutrient-removing microbial communities in two full-scale
      WWTP systems using a new qPCR approach.
AB  - Biological wastewater treatment processes involve very complex microbial
      communities. Culture-independent molecular methods are feasible tools used to
      analyze and control the structure of different microbial communities, such as
      bacterial communities that remove nutrients. Here, we used the gBlocks gene
      fragments method, a new real-time PCR approach for the development of DNA
      standards, to quantify total bacterial cells, AOB, NOB, and Archaeal genes at two
      different WWTPs. PAOs were also quantified using the FISH technique. Our findings
      highlight a significant improvement in real-time PCR detection for the
      microorganisms studied. The qPCR and FISH technique applied allowed
      characterization of the microbial composition of two WWTPs operated as a
      conventional WWTP and a biological nutrient-removal WWTP. The results revealed a
      significant difference in the microbial profiles of the WWTPs, with a higher
      abundance of nitrifying bacterial communities and PAOs in the nutrient removal
      plant, which were in accordance with operational performance.

PMID- 29054665
TI  - Spatial and temporal variations in the atmospheric concentrations of "Stockholm
      Convention" organochlorine pesticides in Kuwait.
AB  - The study reports fortnightly atmospheric concentrations of organochlorine
      pesticides concomitantly measured at an urban, "industrial" and a remote location
      over a twelve month period in Kuwait to examine seasonal variability and urban
      rural concentration gradients. The average+/-SD (and range) of the SigmaOC
      concentrations measured throughout the study period in decreasing order were
      urban, 505+/-305 (range, 33-1352) pgm-3, remote, 204+/-124 (4.5-556) pgm-3, and
      "industrial" 155+/-103 (8.8-533) pgm-3. The concentrations of most OCs measured
      in this study, except for DDT and its metabolites, were higher at urban locations
      relative to their concentrations at remote location, in line with the literature
      on POPs regarding urban conurbations being sources of industrial chemicals. The
      most abundant pesticides measured throughout this study were dieldrin,
      pentachlorobenzene, hexachlorobenzene, SigmaDDTs, SigmaHCHs, and oxychlordane.
      Hexachlorobenzene concentrations were generally higher than those of
      pentachlorobenzene and are both strongly negatively correlated with temperature
      (p<0.05) at all sampling locations. Mean summertime concentrations were higher
      for hexachlorocyclohexanes, chlordanes, dieldrin, and DDT isomers, except for pp
      DDT. This may suggest that concentrations of these compounds may be driven by
      temperature.

PMID- 29054666
TI  - Occurrence and diversity of antibiotic resistance in untreated hospital
      wastewater.
AB  - Antibiotics, antibiotic-resistant bacteria (ARB), antibiotic-resistance genes
      (ARGs), and mobile genetic elements (MGEs) have been reported in many
      environments. However, the investigation of their occurrence and diversity in
      untreated hospital wastewater is still insufficient. High concentrations of
      antibiotic residues were found in hospital wastewater using solid-phase
      extraction and UPLC-MS/MS analysis. The concentrations of six of 14 antibiotics
      reached MUg/L levels in the hospital wastewater, which is higher than reported in
      other aquatic environments. Results of high-throughput sequencing analysis
      indicated that sequences affiliated to genera Escherichia and Acinetobacter were
      the predominant in the cultivable multiple-antibiotic-resistant bacteria (CMARB)
      recovered from the wastewater of three hospitals in China, with compositions of
      34%-74%. Notably, several genera containing clinically pathogenic or
      opportunistic CMARB (e.g., Escherichia, Acinetobacter, Aeromonas, Myroides,
      Enterococcus, Proteus, Pseudomonas, and Streptococcus) were detected at high
      relative abundances in the wastewaters of the three hospitals. High-capacity
      quantitative PCR showed that 131-139 unique ARGs of the 178 targeted genes were
      detected in the hospital wastewaters. The high prevalence of five MGEs and 12
      ARGs was confirmed with qPCR, and some positive correlations between ARGs and
      MGEs were identified, such as between intI1 and qnrD, intI2 and sul3, intI3 and
      tetX, Tn916/Tn1545 and sul2, and ISCR1 and sul3. These results suggest that
      highly abundant antibiotic-resistant pathogens and highly mobile ARGs already
      exist in the human body, and that their release from hospitals without effective
      treatment poses high risks to environments and human health.

PMID- 29054667
TI  - Temperature modulates estrone degradation and biological effects of exposure in
      fathead minnows.
AB  - Environmental pollutants, including estrogens, are widespread in aquatic
      environments frequently as a result of treated wastewater effluent discharged.
      Exposure to estrogens has been correlated with disruption of the normal
      physiological and reproductive function in aquatic organisms, which could impair
      the sustainability of exposed populations. However, assessing the effects of
      estrogen exposure on individuals is complicated by the fact that rates of
      chemical uptake and environmental degradation are temperature dependent. Because
      annual temperature regimes often coincide with critical periods of biological
      activity, temperature-dependent changes in estrogen degradation efficacy during
      wastewater treatment could modulate biological effects. We examined the
      interactions between ambient water temperature and degradation of estrone (E1)
      during wastewater treatment. In addition, we exposed mature fathead minnows
      (Pimephales promelas) to three environmentally relevant concentrations of E1 at
      four different water temperatures (15 degrees C, 18 degrees C, 21 degrees C, and
      24 degrees C) to reflect natural seasonal variation. E1 degradation occurred with
      and without the support of robust nitrification at all temperatures; however, the
      onset of E1 degradation was delayed at cooler water temperatures. In addition, we
      observed significant interactive effects between temperature and E1 exposure.
      Female morphometric endpoints were more susceptible to temperature-modulating
      effects while physiological endpoints were more strongly affected in males.
      Collectively, the data demonstrate that natural seasonal fluctuations in
      temperature are sufficient to affect E1 degradation during wastewater treatment
      and induce sex-dependent physiological and anatomical changes in exposed fish.

PMID- 29054668
TI  - WW LCI v2: A second-generation life cycle inventory model for chemicals
      discharged to wastewater systems.
AB  - We present a second-generation wastewater treatment inventory model, WW LCI 2.0,
      which on many fronts represents considerable advances compared to its previous
      version WW LCI 1.0. WW LCI 2.0 is a novel and complete wastewater inventory model
      integrating WW LCI 1.0, i.e. a complete life cycle inventory, including
      infrastructure requirement, energy consumption and auxiliary materials applied
      for the treatment of wastewater and disposal of sludge and SewageLCI, i.e. fate
      modelling of chemicals released to the sewer. The model is expanded to account
      for different wastewater treatment levels, i.e. primary, secondary and tertiary
      treatment, independent treatment by septic tanks and also direct discharge to
      natural waters. Sludge disposal by means of composting is added as a new option.
      The model also includes a database containing statistics on wastewater treatment
      levels and sludge disposal patterns in 56 countries. The application of the new
      model is demonstrated using five chemicals assumed discharged to wastewater
      systems in four different countries. WW LCI 2.0 model results shows that
      chemicals such as diethylenetriamine penta (methylene phosphonic acid) (DTPMP)
      and Diclofenac, exhibit lower climate change (CC) and freshwater ecotoxicity
      (FET) burdens upon wastewater treatment compared to direct discharge in all
      country scenarios. Results for Ibuprofen and Acetaminophen (more readily
      degradable) show that the CC burden depends on the country-specific levels of
      wastewater treatment. Higher treatment levels lead to lower CC and FET burden
      compared to direct discharge. WW LCI 2.0 makes it possible to generate complete
      detailed life cycle inventories and fate analyses for chemicals released to
      wastewater systems. Our test of the WW LCI 2.0 model with five chemicals
      illustrates how the model can provide substantially different outcomes, compared
      to conventional wastewater inventory models, making the inventory dependent upon
      the atomic composition of the molecules undergoing treatment as well as the
      country specific wastewater treatment levels.

PMID- 29054669
TI  - Impact of copper sulfate application at an urban Brazilian reservoir: A
      geostatistical and ecotoxicological approach.
AB  - A landscape ecotoxicology approach was used to assess the spatial distribution of
      copper in the recent bottom sediment (surficial sediment) of a Brazilian
      subtropical reservoir (the Guarapiranga reservoir) and its potential
      ecotoxicological impacts on the reservoir ecosystem and the local society. We
      discuss the policies and procedures that have been employed for the management of
      this reservoir over the past four decades. Spatial heterogeneity in the reservoir
      was evaluated by means of sampling design and statistical analysis based on
      kriging spatial interpolation. The sediment copper concentrations have been
      converted into qualitative categories in order to interpret the reservoir quality
      and the impacts of management policies. This conversion followed the Canadian
      Water Framework Directive (WFD) ecotoxicological concentration levels approach,
      employing sediment quality guidelines (SQGs). The SQG values were applied as the
      copper concentration thresholds for quantitative-qualitative conversion of data
      for the surficial sediment of the Guarapiranga. The SQGs used were as follows: a)
      interim sediment quality guideline (ISQG), b) probable effect level (PEL), and c)
      regional reference value (RRV). The quantitative results showed that the spatial
      distribution of copper in the recent bottom sediment reflected the reservoir's
      management policy and the copper application protocol, and that the copper
      concentrations varied considerably, ranging from virtually-zero to in excess of
      3gcopper/kgds. The qualitative results demonstrated that the recent bottom
      sediment was predominantly in a bad or very bad condition, and could therefore
      have impacts on the local society and the ecosystem. It could be concluded that
      the management policy for this reservoir was mainly determined by the desire to
      minimize short-term costs, disregarding long-term socioeconomic and environmental
      consequences.

PMID- 29054670
TI  - Risk forewarning model for rice grain Cd pollution based on Bayes theory.
AB  - Cadmium (Cd) pollution of rice grain caused by Cd-contaminated soils is a common
      problem in southwest and central south China. In this study, utilizing the
      advantages of the Bayes classification statistical method, we established a risk
      forewarning model for rice grain Cd pollution, and put forward two parameters
      (the prior probability factor and data variability factor). The sensitivity
      analysis of the model parameters illustrated that sample size and standard
      deviation influenced the accuracy and applicable range of the model. The accuracy
      of the model was improved by the self-renewal of the model through adding the
      posterior data into the priori data. Furthermore, this method can be used to
      predict the risk probability of rice grain Cd pollution under similar soil
      environment, tillage and rice varietal conditions. The Bayes approach thus
      represents a feasible method for risk forewarning of heavy metals pollution of
      agricultural products caused by contaminated soils.

PMID- 29054671
TI  - Impacts of rapid urbanization on the water quality and macroinvertebrate
      communities of streams: A case study in Liangjiang New Area, China.
AB  - Rapid urbanization in China has dramatically deteriorated the water quality of
      streams and threatening aquatic ecosystem health. This study aims to 1) assess
      the impacts of urbanization on water quality and macroinvertebrate composition
      and 2) address the question of how urbanization affects macroinvertebrate
      distribution patterns. Environmental variables over multispatial scales and
      macroinvertebrate community data were collected on April (dry season) and
      September (wet season) of 2014 and 2015 at 19 sampling sites, of which nine had a
      high urbanization level (HUL), six had moderate urbanization level (MUL) and four
      had low urbanization level (LUL), in the Liangjiang New Area. The results of this
      study showed that macroinvertebrate assemblages significantly varied across the
      three urbanization levels. The sensitive species (e.g., EPT taxa) were mainly
      centralized at LUL sites, whereas tolerant species, such as Tubificidae (17.3%),
      Chironomidae (12.1%), and Physidae (4.61%), reached highest relative abundance at
      LUL sites. The values of family biotic index (FBI) and biological monitoring
      working party (BMWP) indicated the deterioration of water quality along
      urbanization gradient. Seasonal and inter - annual changes in macroinvertebrate
      communities were not observed. The results of variation partitioning analyses
      (CCAs) showed that habitat scale variables explained the major variation in
      macroinvertebrate community composition. Specifically, the increased nutrient
      concentrations favored tolerant species, whereas high water flow and substrate
      coarseness benefitted community taxa richness, diversity and EPT richness.
      Considering the interactions between scale-related processes, the results of this
      study suggested that urbanization resulted in less diverse and more tolerant
      stream macroinvertebrate assemblages mainly via increased nutrient concentrations
      and reduced substrate coarseness.

PMID- 29054672
TI  - Optimizing the nitrogen application rate for maize and wheat based on yield and
      environment on the Northern China Plain.
AB  - Optimizing the nitrogen (N) application rate can increase crop yield while
      reducing the environmental risks. However, the optimal N rates vary substantially
      when different targets such as maximum yield or maximum economic benefit are
      considered. Taking the wheat-maize rotation cropping system on the North China
      Plain as a case study, we quantified the variation of N application rates when
      targeting constraints on yield, economic performance, N uptake and N utilization,
      by conducting field experiments between 2011 and 2013. Results showed that the
      optimal N application rate was highest when targeting N uptake (240kgha-1 for
      maize, and 326kgha-1 for wheat), followed by crop yield (208kgha-1 for maize, and
      277kgha-1 for wheat) and economic income (191kgha-1 for maize, and 253kgha-1 for
      wheat). If environmental costs were considered, the optimal N application rates
      were further reduced by 20-30% compared to those when targeting maximum economic
      income. However, the optimal N rate, with environmental cost included, may result
      in soil nutrient mining under maize, and an extra input of 43kgNha-1 was needed
      to make the soil N balanced and maintain soil fertility in the long term. To
      obtain a win-win situation for both yield and environment, the optimal N rate
      should be controlled at 179kgha-1 for maize, which could achieve above 99.5% of
      maximum yield and have a favorable N balance, and at 202kgha-1 for wheat to
      achieve 97.4% of maximum yield, which was about 20kgNha-1 higher than that when N
      surplus was nil. Although these optimal N rates vary on spatial and temporal
      scales, they are still effective for the North China Plain where 32% of China's
      total maize and 45% of China's total wheat are produced. More experiments are
      still needed to determine the optimal N application rates in other regions. Use
      of these different optimal N rates would contribute to improving the
      sustainability of agricultural development in China.

PMID- 29054673
TI  - Fluvial biofilms exposed to desiccation and pharmaceutical pollution: New
      insights using metabolomics.
AB  - In many arid and semi-arid systems, biological communities in river ecosystems
      are submitted to flow interruption and desiccation, as well as to the impact of
      urban wastewaters. In this work, we studied (using a LC-LTQ-Orbitrap) the
      metabolomic response of biofilm communities exposed to both hydrological and
      chemical stressors. Fluvial biofilms were exposed to a mixture of 9
      pharmaceuticals at a total concentration of 5000ng/L (mimicking concentrations
      and compounds found in polluted aquatic environments) and/or to seven days of
      desiccation, under laboratory conditions. The biosynthesis of fatty acids was the
      main metabolic pathway disrupted in biofilms. Endogenous biofilm's metabolites
      (metabolome) altered due to these stressors were identified. The metabolites that
      significantly changed only due to one of the stressors could be proposed as
      potential specific biomarkers. A biomarker of pharmaceutical exposure was the
      lysophosphatidic acid, which decreased a 160%, while for desiccation stearidonic
      acid (increased 160%), 16-Oxohexadecanoic acid (increased 340%) and palmitoleic
      acid (decreased 290%) were the biomarkers proposed. Besides, other metabolites
      showed different responses depending on the treatment, such as palmitic acid,
      linolenic acid, behenic acid, lignoceric acid and azelaic acid. The
      Carbon:Phosphorus (C:P) molar ratio increased due to all stress factors, whereas
      the algal community composition changed mainly due to desiccation. A possible
      relationship between those changes observed in structural parameters and the
      metabolome of biofilms was explored. Overall, our findings support the use of
      metabolomics to unravel at molecular level the effects from chemical and physical
      stressors on complex microbial communities, such as biofilms, and pinpoint
      biomarkers of exposure.

PMID- 29054674
TI  - Bacterial communities in soil become sensitive to drought under intensive
      grazing.
AB  - Increasing climatic and anthropogenic pressures on soil ecosystems are expected
      to create a global patchwork of disturbance scenarios. Some regions will be
      strongly impacted by climate change, others by agricultural intensification, and
      others by both. Soil microbial communities are integral components of terrestrial
      ecosystems, but their responses to multiple perturbations are poorly understood.
      Here, we exposed soils from sustainably- or intensively-managed grasslands in an
      agro-silvo-pastoral oak woodland to month-long intensified drought and flood
      simulation treatments in a controlled mesocosm setting. We monitored the response
      of the bacterial communities at the end of one month as well as during the
      following month of recovery. The communities in sustainably-managed plots under
      all precipitation regimes were richer and more diverse than those in intensively
      managed plots, and contained a lower proportion of rapidly-growing taxa. Soils
      from both land managements exhibited changes in bacterial community composition
      in response to flooding, but only intensively-managed soils were affected by
      drought. The ecologies of bacteria favored by both drought and flood point to
      both opportunism and stress tolerance as key traits shaping the community
      following disturbance. Finally, the response of several taxa (i.e.
      Chloracidobacteria RB41, Janthinobacterium sp.) to precipitation depended on land
      management, suggesting that the community itself affected individual disturbance
      responses. Our findings provide an in-depth view of the complexity of soil
      bacterial community responses to climatic and anthropogenic pressures in time,
      and highlight the potential of these stressors to have multiplicative effects on
      the soil biota.

PMID- 29054676
TI  - Is Diagnostic Performance of Quantitative 2D-Shear Wave Elastography Optimal for
      Clinical Classification of Benign and Malignant Thyroid Nodules?: A Systematic
      Review and Meta-analysis.
AB  - RATIONALE AND OBJECTIVE: This study is a dedicated 2D-shear wave elastography (2D
      SWE) review aimed at systematically eliciting up-to-date evidence of its clinical
      value in differential diagnosis of benign and malignant thyroid nodules. METHODS:
      PubMed, Web of Science, and Scopus databases were searched for studies assessing
      the diagnostic value of 2D-SWE for thyroid malignancy risk stratification
      published until December 2016. The retrieved titles and abstracts were screened
      and evaluated according to the predefined inclusion and exclusion criteria.
      Methodological quality of the studies was assessed using the Quality Assessment
      of Studies of Diagnostic Accuracy included in Systematic Review 2 (QUADAS-2)
      tool. Extracted 2D-SWE diagnostic performance data were meta-analyzed to assess
      the summary sensitivity, specificity, and area under the receiver operating
      characteristic curve. RESULTS: After stepwise review, 14 studies in which 2D-SWE
      was used to evaluate 2851 thyroid nodules (1092 malignant, 1759 benign) from 2139
      patients were selected for the current study. Study quality on QUADAS-2
      assessment was moderate to high. The summary sensitivity, specificity and area
      under the receiver operating characteristic curve of 2D-SWE for differential
      diagnosis of benign and malignant thyroid nodules were 0.66 (95% confidence
      interval [CI]: 0.64-0.69), 0.78 (CI: 0.76-0.80), and 0.851 (Q* = 0.85),
      respectively. The pooled diagnostic odds ratio, negative likelihood ratio, and
      positive likelihood ratio were 12.73 (CI: 8.80-18.43), 0.31 (CI: 0.22-0.44), and
      3.87 (CI: 2.83-5.29), respectively. CONCLUSION: Diagnostic performance of
      quantitative 2D-SWE for malignancy risk stratification of thyroid nodules is
      suboptimal with mediocre sensitivity and specificity, contrary to earlier reports
      of excellence.

PMID- 29054675
TI  - Evidence of fatigue, disordered sleep and peripheral inflammation, but not
      increased brain TSPO expression, in seasonal allergy: A [11C]PBR28 PET study.
AB  - Allergy is associated with non-specific symptoms such as fatigue, sleep problems
      and impaired cognition. One explanation could be that the allergic inflammatory
      state includes activation of immune cells in the brain, but this hypothesis has
      not been tested in humans. The aim of the present study was therefore to
      investigate seasonal changes in the glial cell marker translocator protein
      (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in
      allergy. We examined 18 patients with severe seasonal allergy, and 13 healthy
      subjects in and out-of pollen season using positron emission tomography (n =
      15/13) and the TSPO radioligand [11C]PBR28. In addition, TNF-alpha, IL-5, IL-6,
      IL-8 and IFN-gamma were measured in peripheral blood, and subjective ratings of
      fatigue and sleepiness as well as objective and subjective sleep were
      investigated. No difference in levels of TSPO was seen between patients and
      healthy subjects, nor in relation to pollen season. However, allergic subjects
      displayed both increased fatigue, sleepiness and increased percentage of deep
      sleep, as well as increased levels of IL-5 and TNF-alpha during pollen season,
      compared to healthy subjects. Allergic subjects also had shorter total sleep
      time, regardless of season. In conclusion, allergic subjects are indicated to
      respond to allergen exposure during pollen season with a clear pattern of
      behavioral disruption and peripheral inflammatory activation, but not with
      changes in brain TSPO levels. This underscores a need for development and use of
      more specific markers to understand brain consequences of peripheral inflammation
      that will be applicable in human subjects.

PMID- 29054678
TI  - Excitation characteristic of a bipolar stimulus for broadband stimulation in
      measurements of electrically evoked auditory potentials.
AB  - OBJECTIVE: The aim of this study was to determine the optimum electrical
      stimulation mode for the measurement of electrically evoked potentials. To
      quantify the broadband excitation electrically evoked compound action potentials
      were recorded in cochlear implant recipients. The full width half maximum was
      determined for spread of excitation along the electrode array. DESIGN:
      Prospective clinical study. STUDY SAMPLE: The study sample consisted of 20 adult
      cochlear implant users. RESULTS: The applied alternating, intracochlear
      stimulation mode leads to neural excitation along approximately 80% of the length
      of the electrode array. The median of the full width at half maximum values
      covered the range of 18 electrodes on the implant array. CONCLUSION: The bipolar,
      alternating, and intracochlear stimulation mode would provide a sufficient,
      broadband excitation of the spiral ganglion to measure electrically evoked
      auditory potentials.

PMID- 29054677
TI  - Expression of the PPM1F Gene Is Regulated by Stress and Associated With Anxiety
      and Depression.
AB  - BACKGROUND: Molecular mechanisms underlying psychological sequelae of exposure to
      stressful experiences, such as posttraumatic stress disorder (PTSD) and
      depression, are not well understood. METHODS: Using convergent evidence from
      animal and human transcriptomic and genomic studies, we aimed to identify genetic
      mechanisms underlying depression and anxiety after traumatic experiences.
      RESULTS: From a transcriptome-wide analysis in mice, we found the Ppm1f gene to
      be differentially expressed in the amygdala and medial prefrontal cortex (mPFC) a
      week after immobilization stress. Next, we found that PPM1F messenger RNA levels
      in human blood were downregulated in cases with symptoms of comorbid PTSD and
      depression and consistently in cases with anxiety symptoms in a separate human
      dataset. Furthermore, we showed that a genetic variant of PPM1F, rs17759843, was
      associated with comorbid PTSD and depression and with PPM1F expression in both
      human brain and blood. Given prior reported mechanistic links between PPM1F and
      CAMK2 (CAMKII), we examined blood messenger RNA level of CAMK2G in humans and
      found it to be lower in cases with comorbid PTSD and depression. We also found
      that PPM1F protein levels and colocalization with CAMK2G were altered in amygdala
      and mPFC of male mice. Additionally, we found that a systemic dose of
      corticosterone blocked the depressive-like phenotype elicited by stress in female
      mice. Lastly, corticosterone rescued the anxiety-like phenotype and messenger RNA
      levels of Ppm1f in amygdala and mPFC in male mice and in mPFC of female mice.
      CONCLUSIONS: Taken together, our data suggest a mechanistic pathway involving
      PPM1F and CAMK2G in stress- and trauma-related manifestation of anxiety and
      depression across species.

PMID- 29054679
TI  - Cost-effectiveness analysis of two impression methods for the fabrication of
      mandibular complete dentures.
AB  - OBJECTIVES: To compare the cost and to evaluate cost-effectiveness of fabricating
      mandibular complete dentures (CDs) using two different impression methods.
      METHODS: A crossover randomized controlled trial including 27 edentulous
      participants was performed. Mandibular CDs were fabricated using two different
      impression methods, as follows: (i) conventional method using a custom tray
      border moulded with impression compound and silicone and (ii) simplified method
      using a stock tray and alginate. Cost analysis was performed from a clinical
      practitioner's perspective. The total cost included labor cost, which was
      calculated using the time spent by dentists and technicians in fabricating CDs
      and their hourly wages, and the material costs, which were calculated using
      purchase prices. To evaluate cost-effectiveness, we used general patient
      satisfaction as an indicator of effectiveness and calculated the incremental cost
      effectiveness ratio (ICER). ICER represents the cost per one unit of
      effectiveness. RESULTS: The trial was completed by 24 participants. The total
      cost was 43,904 Japanese Yen (JPY) (330.91 EUR / 395.78 USD) for the conventional
      method and 39,792 JPY (299.93 EUR / 358.70 USD) for the simplified method, and
      this difference was statistically significant (p<0.001). The ICER showed a cost
      of 633 JPY (4.77 EUR / 5.70 USD) for every one point change in general patient
      satisfaction. CONCLUSIONS: The results indicated that the total cost of the
      conventional method was significantly higher than that of the simplified method
      (p<0.001). CLINICAL SIGNIFICANCE: The conventional impression method for
      fabricating mandibular CDs, which took additional 633 JPY (4.77 EUR / 5.70 USD)
      for improvement of general satisfaction, is supposed to be clinically
      meaningful1.

PMID- 29054680
TI  - Phosphorylation of protein phosphatase 2A facilitated an early stage of chemical
      carcinogenesis.
AB  - Protein phosphatase 2A (PP2A) is a serine-threonine phosphatase that regulates
      cell signaling pathways. Its inactivation is correlated with tumor malignancy,
      possibly due to the effects on cell differentiation and malignant cell
      transformation. Therefore, it has been noted that PP2A could be a promising
      target for cancer therapy. In our previous study of the hepatocarcinogen
      estragole (ES), cell proliferation may be required to convert ES-specific DNA
      adducts to mutations. To explore the trigger for cell proliferation, gpt delta
      rats were administered ES by gavage at doses of 3, 30 and 300mg/kg/day for
      4weeks. ES-induced cell proliferation and gene mutations were observed at only
      the high dose whereas ES-specific DNA adducts were detected in a dose-dependent
      manner. Western blot analyses revealed activation of the Akt and ERK pathways
      without activation of upstream regulators, such as c-Raf, PKC and, PI3K.
      Phosphorylation of the PP2A C subunit at Tyr307 was found along with
      phosphorylation of Src. The overall data might imply that PP2A inactivation is
      responsible for cell cycle progression through activation of the Akt and ERK
      pathways at high doses of ES. Based on gamma-H2AX immunohistochemistry and
      Western blot analysis for Rad51 protein, the resultant mutation spectra showed
      large deletion mutations that might result from double strand breaks of DNA.
      Thus, it is likely that inactivation of PP2A resulted in acceleration and
      exacerbation of gene mutations. We conclude that PP2A might contribute to an
      early stage of chemical carcinogenesis, suggesting that PP2A could be a molecular
      target of primary cancer prevention.

PMID- 29054681
TI  - Role of histone acetylation in activation of nuclear factor erythroid 2-related
      factor 2/heme oxygenase 1 pathway by manganese chloride.
AB  - Manganese neurotoxicity is characterized by Parkinson-like symptoms with
      degeneration of dopaminergic neurons in the basal ganglia as the principal
      pathological feature. Manganese neurotoxicity studies may contribute to a good
      understanding of the mechanism of Parkinson's disease (PD). In this study, we
      first confirmed that MnCl2 can promote the expression of nuclear factor erythroid
      2-related factor 2 (Nrf2) protein in the nucleus or cytoplasm while increasing
      the binding activity of Nrf2 and antioxidant response elements, further promoting
      the expression of downstream target gene heme oxygenase 1 (HO-1) and leading to
      increase levels of reactive oxygen species (ROS) and reduce the levels of reduced
      glutathione (GSH). Second, we investigated the role of histone acetylation in the
      activation of Nrf2/HO-1 pathway by manganese chloride in rat adrenal
      pheochromocytoma (PC12) cells. Histone acetyltransferase inhibitor (anacardic
      acid) and histone deacetylase inhibitor (trichostatin A, TSA) were used as
      pretreatment reagents to adjust the level of histone acetylation. Here, we show
      that downregulation of histone acetylation can inhibit Mn-induced Nrf2 nuclear
      translocation and further inhibits the Mn-activated Nrf2/HO-1 pathway. This
      downregulation also promotes manganese-induced increase of ROS and decrease of
      GSH in neurons. These results suggest that the downregulation of histone
      acetylation may play an important role in the neurotoxicity caused by manganese
      and that TSA may provide new ideas and targets in treating manganese-induced
      Parkinson's syndrome and PD.

PMID- 29054682
TI  - Liposomalization of oxaliplatin induces skin accumulation of it, but negligible
      skin toxicity.
AB  - Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs,
      and allows delivery to tumor tissues through passive targeting via an enhanced
      permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil(r),
      Lipo-DXR), a representative liposomal drug, is well-known to reduce
      cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the
      hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of
      its severe adverse effects. We have developed a new liposomal preparation of
      oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal
      cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP
      exhibits increased anti-tumor activity in tumor-bearing mice compared to the
      original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin
      toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l
      OHP promoted accumulation of platinum in rat hind paws, however, it caused
      negligible morphological and histological alterations on the plantar surface of
      the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the
      same distribution profile of dyes into the dermis of hind paws with DXR as in the
      case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty
      PEGylated liposomes or empty PEGylated liposomes caused migration of CD68+
      macrophages into the dermis of hind paws. These findings suggest that the skin
      toxicity on administration of liposomalized drugs is reflected in the
      proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l
      OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP
      preparation leading to an improved quality of life of cancer patients.

PMID- 29054683
TI  - The anthelminthic drug praziquantel is a selective agonist of the sensory
      transient receptor potential melastatin type 8 channel.
AB  - Praziquantel is the most effective anthelminthic drug for the treatment of
      schistosomiasis, an infectious disease caused by the platyhelminth Schistosoma
      mansoni. While praziquantel is known to trigger calcium influx into schisostomes,
      followed by spastic paralysis of the worms and tegumental disruption, the
      mechanism of action of the drug is not completely understood. Although relatively
      well tolerated, praziquantel has been reported to cause mild adverse effects,
      including nausea, abdominal pain and headaches. As a number of putative Transient
      Receptor Potential (TRP) channel genes have recently been predicted in S.
      mansoni, we sought to investigate the effect of praziquantel on three mammalian
      TRP channels, TRP melastatin type 8 (TRPM8), TRP vanilloid type 1 (TRPV1) and TRP
      ankyrin type 1 (TRPA1). Using calcium microfluorimetry and the patch clamp
      technique, we recorded the effect of praziquantel on HEK293T cells expressing
      recombinant TRPM8, TRPV1 or TRPA1, as well as on cultured dorsal root ganglion
      (DRG) neurons from wild type and TRPM8 null mutant mice. We discovered that
      praziquantel is a relatively potent and selective partial agonist of the
      mammalian and avian cold and menthol receptor TRPM8. The activation of cultured
      DRG neurons by clinically relevant concentrations of praziquantel is
      predominantly mediated by TRPM8. Our results may provide clues to a better
      understanding of praziquantel's mechanism of action and its adverse effects.

PMID- 29054684
TI  - Humeral shaft fractures: union outcomes in a large cohort.
AB  - BACKGROUND: Humeral shaft fractures can be managed conservatively or operatively.
      Fracture characteristics were analyzed to identify patients who would benefit
      from early operative fixation. METHODS: We performed a retrospective cohort study
      of 126 consecutive humeral shaft fractures (2008-2015). Fractures were classified
      according to fracture type, location, separation, and comminution. RESULTS: Of
      126 patients, 96 were managed conservatively. In 54%, union occurred before 26
      weeks, and 13% had delayed union after 26 weeks, whereas 33% did not achieve
      union. Of 30 patients managed surgically, 63% had union before 26 weeks, 33% had
      delayed union, and 4% did not achieve union. A statistically significant
      difference favored operative management. This difference was maintained in
      specific fracture patterns (simple and spiral fractures) and locations (proximal-
      or distal-third humeral fractures). Early surgery had a significantly higher
      union rate than delayed surgery. No difference was present between plate and nail
      fixation regarding union or neurologic injury. Separation of fragments, open
      injury, and comminution were not associated with nonunion. A psychiatric history
      (including psychotic disorders, bipolar disorder, multiple involuntary
      psychiatric admissions, or dementia) was significantly associated with nonunion
      after conservative management (P = .016). Two patients with dementia died after
      their conservatively managed fractures progressed to open injuries. CONCLUSION:
      This study found high rates of delayed union and nonunion with conservative
      management. Patients with a significant psychiatric history may benefit from
      consideration of operative intervention.

PMID- 29054685
TI  - Corrective osteotomy for malunion of proximal humerus using a custom-made
      surgical guide based on three-dimensional computer planning: case report.

PMID- 29054686
TI  - Letter to the Editor regarding Westphal T et al: "Axillary nerve lesions after
      open reduction and internal fixation of proximal humeral fractures through an
      extended lateral deltoid-split approach: electrophysiological findings".

PMID- 29054687
TI  - Response to Visser CPJ et al: Letter to the Editor regarding "Axillary nerve
      lesions after open reduction and internal fixation of proximal humerus fractures
      through an extended lateral deltoidsplit approach: electrophysiological
      findings".

PMID- 29054688
TI  - Collagenous matrix supported by a 3D-printed scaffold for osteogenic
      differentiation of dental pulp cells.
AB  - OBJECTIVE: A systematic characterization of hybrid scaffolds, fabricated based on
      combinatorial additive manufacturing technique and freeze-drying method, is
      presented as a new platform for osteoblastic differentiation of dental pulp cells
      (DPCs). METHODS: The scaffolds were consisted of a collagenous matrix embedded in
      a 3D-printed beta-tricalcium phosphate (beta-TCP) as the mineral phase. The
      developed construct design was intended to achieve mechanical robustness owing to
      3D-printed beta-TCP scaffold, and biologically active 3D cell culture matrix
      pertaining to the Collagen extracellular matrix. The beta-TCP precursor
      formulations were investigated for their flow-ability at various temperatures,
      which optimized for fabrication of 3D printed scaffolds with interconnected
      porosity. The hybrid constructs were characterized by 3D laser scanning
      microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and
      compressive strength testing. RESULTS: The in vitro characterization of scaffolds
      revealed that the hybrid beta-TCP/Collagen constructs offer superior DPCs
      proliferation and alkaline phosphatase (ALP) activity compared to the 3D-printed
      beta-TCP scaffold over three weeks. Moreover, it was found that the incorporation
      of TCP into the Collagen matrix improves the ALP activity. SIGNIFICANCE: The
      presented results converge to suggest the developed 3D-printed beta-TCP/Collagen
      hybrid constructs as a new platform for osteoblastic differentiation of DPCs for
      craniomaxillofacial bone regeneration.

PMID- 29054689
TI  - Breast Cancer Survivorship Care Variations Between Adjuvant Chemotherapy
      Regimens.
AB  - BACKGROUND: Treatment-related toxicity can vary substantially between
      chemotherapy regimens. In this study we evaluated the frequency of outpatient
      office visits among a cohort of early stage breast cancer survivors after
      completion of 4 different adjuvant chemotherapy regimens to better understand how
      differences in toxicities between regimens might affect health care use.
      MATERIALS AND METHODS: We analyzed administrative claims data from a US
      commercial insurance database (OptumLabs) to identify women who received adjuvant
      doxorubicin/cyclophosphamide (AC), AC followed or preceded by docetaxel or
      paclitaxel (AC-T), AC concurrent with docetaxel or paclitaxel (TAC), or
      docetaxel/cyclophosphamide (TC) between 2008 and 2014. We compared mean numbers
      of visits per patient (adjusted for age, race/ethnicity, region, year, surgery
      type, radiation, chronic conditions, and previous hospitalizations) across the
      different regimens (TC = reference) for 12 months, starting 4 months after the
      end of chemotherapy. RESULTS: In 6247 eligible patients, the mean adjusted number
      of outpatient visits per patient was significantly higher in patients who
      received AC-T (8.1) or TAC (7.3) than TC (6.5) or AC (6.0; P < .001 for
      comparisons of AC-T and TAC with TC), primarily because of differences in Medical
      Oncology visits. Approximately 40% did not see a primary care provider at all
      during this time frame. CONCLUSIONS: AC-T and TAC are associated with more
      subsequent outpatient visits than TC. Visits to primary care providers are
      infrequent during the year after completion of chemotherapy.

PMID- 29054690
TI  - Removable Rigid Dressings for Postoperative Management of Transtibial
      Amputations: A Review of Published Evidence.
AB  - : Forty years of clinical experience and peer-reviewed research studies support
      the use of nonweight-bearing removable rigid dressings (RRDs) as an effective
      means of postoperative management of transtibial amputations. We reviewed the
      published medical evidence regarding the use of RRDs as a postoperative
      management strategy, culminating in an evidence-based practice recommendation.
      Published peer-reviewed literature on the topic was searched and classified by
      level of evidence based on the research design using the scale recommended by the
      PM&R (level I through V). The search uncovered a total of 15 articles, including
      5 level I randomized controlled trials, 6 level III retrospective matched
      controlled trials, and 4 level V case reports. A number of benefits associated
      with the application of RRDs compared with soft dressings were reported across
      these 15 studies. These included faster healing times, reduced limb edema,
      preparatory contouring of the residual limb in anticipation of prosthetic use,
      the prevention of knee flexion contractures, and reduced external trauma to the
      limb. Also described were an increased probability of successful prosthetic use
      and pain reduction. The RRDs studied permitted regular inspection of surgical
      wounds with greater ease and consistency of application than traditional soft
      dressing approaches. Rigid dressings provide all the same benefits of RRDs except
      ease of wound inspection, therefore rendering them impractical for the 82% of
      patients receiving an amputation for ischemic disease that are at high risk of
      developing wound dehiscence. Weight-bearing immediate postoperative prostheses
      are almost exclusively reserved for use on trauma patients who usually do not
      show evidence of vascular or neurologic impairment. The inherent risks of falls
      and inconsistent pressure on the surgical wound have further restricted their use
      in practice to a limited patient type. The benefits of RRDs compared with soft
      dressings are universally recognized in the published peer-reviewed medical
      evidence to be superior to soft dressings. Based on the best-available current
      published evidence, nonweight-bearing removable rigid dressings should be
      considered the first treatment choice for the postoperative care of transtibial
      amputees to optimize outcomes with regard to reductions in injury due to falls,
      knee flexion contractures, edema, healing time, time to prosthetic fitting, and
      pain. LEVEL OF EVIDENCE: II.

PMID- 29054691
TI  - Impact of Critical Illness Polyneuromyopathy in Rehabilitation: A Prospective
      Observational Study.
AB  - BACKGROUND: Critical illness polyneuromyopathy (CIPNM) increasingly is recognized
      as a source of disability in patients requiring intensive care unit (ICU)
      admission. The prevalence and impact of CIPNM on patients in the rehabilitation
      setting has not been established. OBJECTIVES: To determine the proportion of at
      risk rehabilitation inpatients with evidence of CIPNM and the functional sequelae
      of this disorder. DESIGN: Prospective observational study. SETTING: Tertiary
      academic rehabilitation hospital. PATIENTS: Rehabilitation inpatients with a
      history of ICU admission for at least 72 hours. METHODS: Electrodiagnostic
      studies were performed to evaluate for axonal neuropathy and/or myopathy in at
      least one upper and one lower limb. MAIN OUTCOME MEASUREMENTS: The primary
      outcome was prevalence of CIPNM. Secondary outcomes included Functional
      Independence Measure (FIM) scores, rehabilitation length of stay (RLOS), and
      discharge disposition. RESULTS: A total of 33 participants were enrolled; 70% had
      evidence of CIPNM. Admission FIM score, discharge FIM, FIM gain, and FIM
      efficiency were 64.1, 89.9, 25.5, and 0.31 in those with CIPNM versus 78.4, 94.6,
      16.1, and 0.33 in those without CIPNM, respectively. Average RLOS was 123 days
      versus 76 days and discharge to home was 57% versus 90% in the CIPNM and non
      CIPNM groups, respectively. CONCLUSIONS: CIPNM is very common in rehabilitation
      inpatients with a history of ICU admission. It was associated with a lower
      functional status at rehabilitation admission, but functional improvement was at
      a similar rate to those without CIPNM. Longer RLOS stay may be required to
      achieve the same functional level. LEVEL OF EVIDENCE: III.

PMID- 29054692
TI  - Plasmacytoid dendritic cells drive acute asthma exacerbations.
AB  - BACKGROUND: Although acute exacerbations, mostly triggered by viruses, account
      for the majority of hospitalizations in asthmatic patients, there is still very
      little known about the pathophysiologic mechanisms involved. Plasmacytoid
      dendritic cells (pDCs), prominent cells of antiviral immunity, exhibit
      proinflammatory or tolerogenic functions depending on the context, yet their
      involvement in asthma exacerbations remains unexplored. OBJECTIVES: We sought to
      investigate the role of pDCs in allergic airway inflammation and acute asthma
      exacerbations. METHODS: Animal models of allergic airway disease (AAD) and virus
      induced AAD exacerbations were used to dissect pDC function in vivo and unwind
      the potential mechanisms involved. Sputum from asthmatic patients with stable
      disease or acute exacerbations was further studied to determine the presence of
      pDCs and correlation with inflammation. RESULTS: pDCs were key mediators of the
      immunoinflammatory cascade that drives asthma exacerbations. In animal models of
      AAD and rhinovirus-induced AAD exacerbations, pDCs were recruited to the lung
      during inflammation and migrated to the draining lymph nodes to boost TH2
      mediated effector responses. Accordingly, pDC depletion after allergen challenge
      or during rhinovirus infection abrogated exacerbation of inflammation and
      disease. Central to this process was IL-25, which was induced by allergen
      challenge or rhinovirus infection and conditioned pDCs for proinflammatory
      function. Consistently, in asthmatic patients pDC numbers were markedly increased
      during exacerbations and correlated with the severity of inflammation and the
      risk for asthma attacks. CONCLUSIONS: Our studies uncover a previously
      unsuspected role of pDCs in asthma exacerbations with potential diagnostic and
      prognostic implications. They also propose the therapeutic targeting of pDCs and
      IL-25 for the treatment of acute asthma.

PMID- 29054693
TI  - Project Octo-Pills - A practice model engaging community pharmacists in the care
      of patients from a tertiary hospital.
AB  - Even while pharmacy practice evolves to a more patient-centric mode of practice,
      local hospitals, due to high patient load as well as space and resource
      constraints, find it challenging to conduct thorough medication review and
      physical medication reconciliation for all patients. In light of this, optimizing
      the local current healthcare system to involve community pharmacists in the care
      of patients from public hospitals could potentially better cater to the
      healthcare needs of the older population. Due to easy accessibility, community
      pharmacies are often the first point of contact in the healthcare system. Project
      Octo-Pills aims to engage community pharmacists in the collaborative care of
      patients from a tertiary hospital, providing patients with quality medication
      reconciliation and review services from a more convenient location within their
      neighborhood. This paper describes the model for this pilot initiative.

PMID- 29054694
TI  - The resilient brain and the guardians of sleep: New perspectives on old
      assumptions.
AB  - Resilience is the capacity of a system, enterprise or a person to maintain its
      core purpose and integrity in the face of dramatically changed circumstances. In
      human physiology, resilience is the capacity of adaptively overcoming stress and
      adversity while maintaining normal psychological and physical functioning. In
      this review, we investigate the resilient strategies of sleep. First, we discuss
      the concept of brain resilience, highlighting the modular structure of small
      world networking, neuronal plasticity and critical brain behavior. Second, we
      explore the contribution of sleep to brain resilience listing the putative
      factors that impair sleep quality and predict susceptibility to sleep disorders.
      The third part details the manifold mechanisms acting as guardians of sleep,
      i.e., homeostatic, circadian and ultradian processes, sleep microstructure (K
      complexes, delta bursts, arousals, cyclic alternating pattern, spindles),
      gravity, muscle tone and dreams. Mapping and pooling together the guardians of
      sleep in a dynamic integrated framework might lead towards an objective measure
      of sleep resilience and identify effective personalized strategies (biological,
      pharmacological, behavioral) to restore or protect the core properties of healthy
      sleep.

PMID- 29054695
TI  - Where does meniscal damage progress most rapidly? An analysis using three
      dimensional shape models on data from the Osteoarthritis Initiative.
AB  - OBJECTIVES: Meniscal pathology is integral to knee osteoarthritis (OA) and its
      progression; it provides a progression biomarker and a potential treatment
      target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in
      meniscal damage; this structural complexity means measurement is difficult. The
      aim of this study was to apply novel 3D image analysis to determine which
      meniscal pathologies demonstrated most change during OA progression. METHODS:
      Knee images were selected from the progression cohort of the Osteoarthritis
      Initiative choosing participants with risk factors for medial OA progression.
      Medial and lateral menisci were manually segmented then analysed using a
      statistical shape model of the tibia as a reference surface. Responsiveness was
      assessed at 1 year using standardised response means (SRMs) for four constructs:
      meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub
      regions of these constructs were also explored. RESULTS: Paired images from 86
      participants (median age 61.5, 49% female, 56% obese) were included. Reliability
      of the novel meniscal measurements was very good intraclass correlation
      coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no
      significant change. Moderate responsiveness was observed for medial meniscus
      thickness (SRM -0.35) and medial tibial coverage (SRM -0.36). No substantial
      change was seen for the lateral meniscus measures. Sub-region analysis did not
      improve responsiveness; while greater change was seen in the posterior medial
      compartment, it was associated with increased variance of the change.
      CONCLUSIONS: The location of meniscal damage was consistently in the posterior
      medial region, and two measurements (thickness and tibial coverage) were most
      responsive. Meniscal measures should add to discriminatory power in OA
      progression assessment.

PMID- 29054696
TI  - Effects of articaine on [3H]noradrenaline release from cortical and spinal cord
      slices prepared from normal and streptozotocin-induced diabetic rats and compared
      to lidocaine.
AB  - Since a significant proportion of diabetic patients have clinical or subclinical
      neuropathy, there may be concerns about the use of local anaesthetics. The
      present study was designed to determine and compare the effects of articaine, a
      widely used anaesthetic in dental practice, and lidocaine on the resting and
      axonal stimulation-evoked release of [3H]noradrenaline ([3H]NA) in prefrontal
      cortex slices and the release of [3H]NA in spinal cord slices prepared from non
      diabetic and streptozocin (STZ)-induced diabetic (glucose level=22.03+/
      2.31mmol/l) rats. The peak of allodynia was achieved 9 weeks after STZ-treatment.
      Articaine and lidocaine inhibited the stimulation-evoked release in a
      concentration-dependent manner and increased the resting release by two to six
      times. These effects indicate an inhibitory action of these anaesthetics on Na+-
      and K+-channels. There was no difference in clinically important nerve conduction
      between non-diabetic and diabetic rats, as measured by the release of transmitter
      in response to axonal stimulation. The uptake and resting release of NA was
      significantly higher in the brain slices prepared from diabetic rats, but there
      were no differences in the spinal cord. For the adverse effects, the effects of
      articaine on K+ channels (resting release) are more pronounced compared to
      lidocaine. In this respect, articaine has a thiophene ring with high lipid
      solubility, which may present potential risks for some patients.

PMID- 29054697
TI  - A novel method for oxygen glucose deprivation model in organotypic spinal cord
      slices.
AB  - This study aimed to establish a model to closely mimic spinal cord hypoxic
      ischemic injury with high production and high reproducibility. Fourteen-day
      cultured organotypic spinal cord slices were divided into 4 groups: control
      (Ctrl), oxygen glucose deprived for 30min (OGD 30min), OGD 60min, and OGD 120min.
      The Ctrl slices were incubated with 1ml propidium iodide (PI) solution (5MUg/ml)
      for 30min. The OGD groups were incubated with 1ml glucose-free DMEM/F12 medium
      and 5MUl PI solution (1mg/ml) for 30min, 60min and 120min, respectively. Positive
      control slice was fixed by 4% paraformaldehyde for 20min. The culture medium in
      each group was then collected and the Lactate Dehydrogenase (LDH) level in the
      medium was tested using Multi-Analyte ELISArray kits. Structure and refraction of
      the spinal cord slices were observed by light microscope. Fluorescence intensity
      of PI was examined by fluorescence microscopy and was tested by IPP Software.
      Morphology of astrocytes was observed by immunofluorescence histochemistry.
      Caspase 3 and caspase 3 active in different groups were tested by Western blot.
      In the OGD groups, the refraction of spinal cord slices decreased and the
      structure was unclear. The changes of refraction and structure in the OGD 120min
      group were similar to that in the positive control slice. Astrocyte morphology
      changed significantly. With the increase of OGD time, processes became thick and
      twisted, and nuclear condensations became more apparent. Obvious changes in
      morphology were observed in the OGD 60min group, and normal morphology
      disappeared in the OGD 120min group. Fluorescence intensity of PI increased along
      with the extension of OGD time. The difference was significant between 30min and
      60min, but not significant between 60min and 120min. The intensity at OGD 120min
      was close to that in the positive control. Compare with the Ctrl group, the OGD
      groups had significantly higher LDH levels and caspase 3 active/caspase 3 ratios.
      The values increased with the extension of OGD time and reached peak at 120min.
      The increase was significant between 30min and 60min, but not significant between
      60min and 120min. Organotypic spinal cord slices cultured in glucose-free medium
      and anaerobic incubator could mimic hypoxia-ischemia of the spinal cord
      perfectly; 60min could be the best duration for OGD. This technique might be a
      simple and efficient method to obtain in vitro model for spinal cord hypoxic
      ischemic injury in sufficient number and with high quality.

PMID- 29054698
TI  - Visual and Quantitative Electroencephalographic Analysis in Healthy Term Neonates
      Within the First Six Hours and the Third Day of Life.
AB  - BACKGROUND: What constitutes a "normal" background electroencephalography (EEG)
      rhythm immediately after birth is not well understood. We performed video
      electroencephalography recordings in the first six hours (first measure) and the
      third day of life (second measure) for evidence of transient changes in brain
      function. METHODS: We performed a cohort study of an incidental sample of healthy
      term neonates in a single-center nursery. Main outcome measures were as follows:
      (1) EEG visual analysis, which included sleep-wake cycles, proportions of
      discontinuity and bursts with delta brushes, and number per hour of alpha/theta
      rolandic activity, encoches frontales, and transients; and (2) the
      electroencephalographic spectral analysis, which included power spectrum in the
      following frequency bands: delta, 0.5 to 4 Hz; theta, 4 to 8 Hz; alpha, 8 to 13
      Hz; and beta, 13 to 30 Hz. Theta/delta and alpha/delta ratios were also
      calculated. RESULTS: Twenty-two babies were enrolled. Significant findings (P <
      0.05) in the first six hours with respect to 48 to 72 hours of life were (1)
      increased discontinuity, indeterminate sleep, and bursts with delta brushes; (2)
      higher number of transients, and lower number of alpha/theta rolandic activity
      and encoches frontales. Minimal changes were found in power spectrum data.
      However, using receiver operating characteristic curve analysis, theta/delta
      ratio <=0.484 was the best cutoff to discriminate between the two measures
      (positive predictive value, 100.0; 95% confidence interval 71.0 to 100).
      CONCLUSIONS: In healthy term neonates, immature electroencephalographic patterns,
      lack of clearly defined sleep-wake cycles, and frequent transients can be
      considered normal electroencephalographic findings in the first six hours of
      life. Normative power spectrum data are provided. These findings suggest that
      neonatal adaptation immediately after birth leads to transient changes in brain
      function.

PMID- 29054699
TI  - Silymarin attenuated paraquat-induced cytotoxicity in macrophage by regulating
      Trx/TXNIP complex, inhibiting NLRP3 inflammasome activation and apoptosis.
AB  - Oxidative stress and inflammation are involved in paraquat-induced cytotoxicity.
      Silymarin can exert a potent antioxidative and anti-inflammatory effect in
      various pathophysiological processes. The aim of this current study is to explore
      the protective effect and potential mechanism of silymarin in paraquat-induced
      macrophage injury. Cells were pretreated with different doses of silymarin for 3h
      before exposure to paraquat. At 24h after exposure to paraquat, the paraquat
      induced cytotoxicity to macrophage was measured via the MTT assay and LDH
      release. The levels of intracellular reactive oxygen species, GSH-Px, SOD, and
      lipid peroxidation product malondialdehyde were measured to evaluate the
      oxidative effect of paraquat. NLRP3 inflammasome and cytokines secretion in
      macrophage exposed to paraquat at 24h were measured via immunofluorescence
      microscopy, western blot or Elisa. Our results revealed that paraquat could
      dramatically cause cytotoxicity and reactive oxygen species generation, enhance
      TXNIP expression, and induce NLRP3 inflammasome activation and cytokines
      secretion. The pretreatment with silymarin could remarkably reduce the
      cytotoxicity, promote the expression of Trx and antioxidant enzymes, and suppress
      the TXNIP and NLRP3 inflammasome activation. In conclusion, silymarin attenuated
      paraquat-induced cytotoxicity in macrophage by inhibiting oxidative stress, NLRP3
      inflammasome activation, cytokines secretion and apoptosis.

PMID- 29054700
TI  - Rebamipide suppresses 5-fluorouracil-induced cell death via the activation of
      Akt/mTOR pathway and regulates the expression of Bcl-2 family proteins.
AB  - Oral mucositis is a common adverse effect of chemotherapy that limits the
      required dose of chemotherapeutic agents. Numerous attempts to mitigate
      chemotherapy-induced oral mucositis have failed to identify an appropriate
      treatment. Recently, it has been indicated that rebamipide prevents
      chemoradiotherapy-induced oral mucositis in patients. However, the details of the
      underlying mechanism involved in the cytoprotective effect of rebamipide remain
      obscure. In the present study, we investigated the mechanism behind rebamipide
      cytoprotective effect in the oral mucosa using primary normal human oral
      keratinocytes (NHOK cells). We found that rebamipide prevented 5-fluorouracil (5
      FU)-induced cell death in NHOK cells. In addition, rebamipide increased the
      levels of phosphorylated Akt and mTOR, enhanced the Bcl-2 and Bcl-xL expressions,
      and suppressed the expression of Bax and Bim. This is in contrast to 5-FU-induced
      suppression of Akt and mTOR activation, Bcl-2 and Bcl-xL expressions, and the
      enhanced expression of Bax and Bim. These findings suggest that rebamipide can
      potentially be used for the protection of oral mucosa from chemotherapy-induced
      mucositis. This is the first study that elucidates the specific molecular pathway
      for the cytoprotective effect of rebamipide.

PMID- 29054701
TI  - Intra- and inter-laboratory reproducibility and predictivity of the HaCaSens
      assay: A skin sensitization test using human keratinocytes, HaCaT.
AB  - Due to considerable constraints in using animals for risk assessment, much effort
      has been directed at developing non-animal test methods. Developing assays for
      skin sensitization, the leading cause of contact dermatitis, is particularly
      important, but there are currently no in vitro skin sensitization tests that
      completely replace animal tests. HaCaSens, a simple skin sensitization test using
      non-transformed HaCaT cells, predicts keratinocyte activation by skin sensitizers
      with 75% sensitivity, 83% specificity and 77% accuracy in a previous study using
      22 coded substances. Although the data show promising results, the number of
      tested substances is insufficient to prove predictive capacity. Moreover,
      reproducibility among different laboratories has not been studied. Here, three
      laboratories participated in a validation in order to assess HaCaSens feasibility
      for official validation. To examine transferability, intra- and inter-lab
      reproducibility and predictive capacity, HaCaSens was assessed on a set of 30
      test substances coordinated by the Validation Management Team (VMT). The results
      showed satisfactory transferability as well as intra- and inter-laboratory
      reproducibility. Further assessment of its predictive capacity on 20 test
      substances demonstrated a sensitivity of 81.8% (18/22), specificity of 87.5%
      (7/8), and accuracy of 83.3% (25/30) in identifying skin sensitizers, which is
      comparable with presently validated assays, KeratinoSensTM and LuSens. This
      validation study shows that the HaCaSens assay is easily transferable,
      reproducible and highly predictable for identifying skin sensitizers.

PMID- 29054702
TI  - Year in review: Work of Leadership Council for 2017.

PMID- 29054703
TI  - Comment on: laparoscopic sleeve gastrectomy combined with Rossetti fundoplication
      (R-sleeve) for treatment of morbid obesity and gastroesophageal reflux.

PMID- 29054704
TI  - Comment on: Single stage conversion from adjustable gastric banding to sleeve
      gastrectomy or Roux-en-Y gastric bypass: an analysis of 4875 patients.

PMID- 29054705
TI  - Cistanches Herba: An overview of its chemistry, pharmacology, and
      pharmacokinetics property.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cistanches Herba is an Orobanchaceae parasitic
      plant. As a commonly used Traditional Chinese Medicine (TCM), its traditional
      functions include treating kidney deficiency, impotence, female infertility and
      senile constipation. Chemical analysis of Cistanches Herba revealed that
      phenylethanoid glycosides, iridoids, lignans, oligosaccharides, and
      polysaccharides were the main constituents. Pharmacological studies demonstrated
      that Cistanches Herba exhibited neuroprotective, immunomodulatory, hormonal
      balancing, anti-fatigue, anti-inflammatory, hepatoprotection, anti-oxidative,
      anti-bacterial, anti-viral, and anti-tumor effects, etc. The aim of this review
      is to provide updated, comprehensive and categorized information on the
      phytochemistry, pharmacological research and pharmacokinetics studies of the
      major constituents of Cistanches Herba. MATERIALS AND METHODS: The literature
      search was conducted by systematic searching multiple electronic databases
      including SciFinder, ISI Web of Science, PubMed, Google Scholar and CNKI.
      Information was also collected from journals, local magazines, books, monographs.
      RESULTS: To date, more than 100 compounds have been isolated from this genus,
      include phenylethanoid glycosides, carbohydrates, lignans, iridoids, etc. The
      crude extracts and isolated compounds have exhibited a wide range of in vitro and
      in vivo pharmacologic effects, such as neuroprotective, immunomodulatory, anti
      inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, and anti-tumor
      effects. The phenylethanoid glycosides, echinacoside and acteoside have attracted
      the most attention for their significantly neuropharmacology effects.
      Pharmacokinetic studies of echinacoside and acteoside also have also been
      summarized. CONCLUSION: Phenylethanoid glycosides have demonstrated wide
      pharmacological actions and have great clinical value if challenges such as poor
      bioavailability, fast and extensive metabolism are addressed. Apart from
      phenylethanoid glycosides, other constituents of Cistanches Herba, their
      pharmacological activities and underlying mechanisms are also need to be studied
      further.

PMID- 29054706
TI  - Quality of life for parents of children with food allergy in peanut-restricted
      versus peanut-free schools in the United States and Canada.

PMID- 29054707
TI  - Bitter and sweet taste tests are reflective of disease status in chronic
      rhinosinusitis.

PMID- 29054708
TI  - Semantic analysis of thyroid cancer cell proteins obtained from rare research
      opportunities.
AB  - Research in natural sciences is mainly done by means of experiments. Some of
      those experiments such as spaceflight-dependent experiments are extremely
      laborious, complex and expensive. Hence, they often remain rare events with
      little chances of statistical tests and possibilities of repetition. In order to
      make each single event as valuable as possible, a sophisticated comparison of
      experimental data received with the hundreds of millions of computer-stored
      documents appears necessary. We used results of an earlier study on proteome
      analysis of microgravity-exposed human thyroid cancer cells, selected twenty
      proteins which appeared gravity sensitive and investigated whether their change
      observed in cells under the loss of gravity could cause health problems in
      astronauts. Using network analysis via Knowledge Explorer (KE) we searched the
      literature for diseases related to one or more of the selected proteins. After
      using Linked Open Data (LOD) and other public resources to establish a
      comprehensive semantic knowledgebase around functional properties of the selected
      proteins, the collection's network was used to query a set of databases for the
      proteins' involvement in biosystems and human diseases. Finally, possible
      countermeasures could be proposed.

PMID- 29054709
TI  - Comparing the historical limits method with regression models for weekly
      monitoring of national notifiable diseases reports.
AB  - To compare the performance of the standard Historical Limits Method (HLM), with a
      modified HLM (MHLM), the Farrington-like Method (FLM), and the Serfling-like
      Method (SLM) in detecting simulated outbreak signals. We used weekly time series
      data from 12 infectious diseases from the U.S. Centers for Disease Control and
      Prevention's National Notifiable Diseases Surveillance System (NNDSS). Data from
      2006 to 2010 were used as baseline and from 2011 to 2014 were used to test the
      four detection methods. MHLM outperformed HLM in terms of background alert rate,
      sensitivity, and alerting delay. On average, SLM and FLM had higher sensitivity
      than MHLM. Among the four methods, the FLM had the highest sensitivity and lowest
      background alert rate and alerting delay. Revising or replacing the standard HLM
      may improve the performance of aberration detection for NNDSS standard weekly
      reports.

PMID- 29054710
TI  - Novel p-carborane-containing multitarget anticancer agents inspired by the
      metabolism of 17beta-estradiol.
AB  - The female hormone 17 beta-estradiol (E2) is synthesized from estrone by steroid
      sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the
      biological activity of the latter is substantially different from that of E2.
      Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and
      its derivatives (1 and 2) were designed and synthesized as novel multitarget
      anticancer agents. Bissulfamate 1f exhibited potent STS-inhibitory activity and
      tubulin-polymerization-inhibitory activity. Moreover, the cell-growth-inhibitory
      (CGI) activity of 1f was similar to that of 2-ME in a panel screening against 39
      human cancer cell lines. Accordingly, 1f should be a promising perspective
      therapeutic agent for hormone-dependent breast tissue.

PMID- 29054711
TI  - High throughput photo-oxidations in a packed bed reactor system.
AB  - The efficiency gains produced by continuous-flow systems in conducting
      photochemical transformations have been extensively demonstrated. Recently, these
      systems have been used in developing safe and efficient methods for photo
      oxidations using singlet oxygen generated by photosensitizers. Much of the
      previous work has focused on the use of homogeneous photocatalysts. The
      development of a unique, packed-bed photoreactor system using immobilized rose
      bengal expands these capabilities as this robust photocatalyst allows access to
      and elaboration from these highly useful building blocks without the need for
      further purification. With this platform we were able to demonstrate a wide scope
      of singlet oxygen ene, [4+2] cycloadditions and heteroatom oxidations.
      Furthermore, we applied this method as a strategic element in the synthesis of
      the high-volume antimalarial artemisinin.

PMID- 29054712
TI  - [Spontaneous pneumomediastinum: A rare complication of dermatomyositis].
AB  - Dermatomyositis is a rare connective tissue disease of unknown origin, including
      inflammatory myopathy and cutaneous manifestations. Several pulmonary
      complications associated to dermatomyositis were described; especially
      interstitial lung disease. Some rare and particular pulmonary complications were
      reported in the literature such as pneumodiastinum and pneumothorax. We are
      describing here, a case report about a female patient, who presented with
      dermatomyositis associated to pneumomediastinum as a severe and lethal
      complication without pneumothorax. It is a novel observation depicting this
      severe and rare complication. Brutal dyspnea and cervical subcutaneous crackling
      are alarming signs that should make practitioners think about this complication.

PMID- 29054713
TI  - [An endobronchial fistula revealing tuberculosis: Atypical presentation in
      France].

PMID- 29054714
TI  - [Extra-pleural hematoma: The extra-pleural fat sign].

PMID- 29054715
TI  - [Negative pressure pulmonary edema following a cholecystectomy - A case report].
AB  - Negative pressure pulmonary edema (NPPE) or post-obstructive pulmonary edema
      (POPE) is a rare but a life threatening respiratory situation. The most frequent
      cause of NPPE is a post anesthetic laryngospasm. Edema is developed after relief
      of upper airway obstruction. Its incidence is 0.1 % of general anesthesia with
      tracheal intubation. We report this clinical case of a 28-year-old woman, who
      developed dyspnea followed by acute respiratory distress with unilateral
      pulmonary edema after extubation following general anesthesia for cholecystectomy
      under celioscopy. After elimination of any other cause, context, clinical and
      radiological characteristics, and the favorable evolution under oxygen and
      furosemide made it possible for us to link this acute respiratory distress to a
      NPPE whose pathophysiological causes and mechanisms are discussed.

PMID- 29054716
TI  - [The surgery of diaphragmatic hydatidosis and their complications].
AB  - Primary or secondary diaphragmatic echinococcosis is rare, accounting for 1% of
      the thoracic locations. They may be operative discovery or by their complication,
      hence a variable symptomatology making this localization a particular entity. The
      thoracic and abdominal CT allows a complete assessment. Surgery remains the only
      therapeutic approach. In complicated forms an additional surgery is required for
      complete care. The prognosis is generally good apart from the risk of recurrence.
      Through a series of 4 operated patients, we focus on the clinical and therapeutic
      features of this pathology and its complications.

PMID- 29054717
TI  - [Evaluation of quality of life (QOL) of Tunisians patients with COPD].
AB  - AIM: To test the Arabic version of the St. George's Hospital Respiratory
      Questionnaire (SGRQ) in stable Tunisian COPD patients. HYPOTHESES: A correlation
      coefficient between the post-bronchodilator FEV1 and the "Total" score of SGRQ
      higher than "-0.40", and QOL scores lower in COPD with "mild to moderate airway
      obstruction" than in those with "severe to very severe airway obstruction" will
      be in favor of a possible application of the Arabic version of the SGRQ in
      Tunisians COPD patients. METHODS: This is a prospective cross-sectional study
      including 50 clinically stable COPD patients. The Arabic version of the SGRQ was
      used. Four scores were calculated for the "Symptoms", "Activities", "Impacts" and
      "Total" components. Patients were divided into two groups according to the
      severity of their airway obstruction: "mild to moderate, n=30" and "severe to
      very severe, n=20". The correlation between the QOL "Total" score and postBD FEV1
      was evaluated. RESULTS: The mean+/-SD of age, cigarette smoking and post
      bronchodilator FEV1 were, respectively, 60+/-10, 61+/-36 pack-years and 55+/-20
      %. The correlation between the post-bronchodilator FEV1 and QOL "Total" score was
      significant at "-0.65". "Symptoms", "Activities", "Impacts" and "Total" scores
      were significantly less altered in patients with "mild to moderate airway
      obstruction" than among those with "severe to very severe airway obstruction"
      (respectively, 52+/-24 vs. 77+/-17, 66+/-28 vs. 87+/-18, 48+/-25 vs. 70+/-23 and
      54+/-22 vs. 76+/-17). CONCLUSION: The application of the Arabic version of the
      SGRQ in stable COPD patients gives reliable results.

PMID- 29054719
TI  - Two cases of distal ulna giant cell tumors treated by extensive resection,
      prosthetic reconstruction and stabilization using the brachioradialis tendon.
AB  - Aggressive giant cell tumors are rare at the distal ulna. We report the results
      of two patients who were treated surgically using a distal ulna prosthesis
      stabilized by ligament reconstruction with the brachioradialis tendon. At the
      maximum follow-up of 18months, the two patients were satisfied. Joint range of
      motion and functional scores were improved. X-rays showed no recurrence or
      subluxation; however gradual impingement of the ulnar notch of radius by the
      prosthesis was visible. Our technique seems to be a viable alternative when
      compared with the treatments described in other published case reports.

PMID- 29054718
TI  - Determination of the impact of melanoma surgical timing on survival using the
      National Cancer Database.
AB  - BACKGROUND: The ideal timing for melanoma treatment, predominantly surgery,
      remains undetermined. Patient concern for receiving immediate treatment often
      exceeds surgeon or hospital availability, requiring establishment of a safe
      window for melanoma surgery. OBJECTIVE: To assess the impact of time to
      definitive melanoma surgery on overall survival. METHODS: Patients with stage I
      to III cutaneous melanoma and with available time to definitive surgery and
      overall survival were identified by using the National Cancer Database (N =
      153,218). The t test and chi-square test were used to compare variables. Cox
      regression was used for multivariate analysis. RESULTS: In a multivariate
      analysis of patients in all stages who were treated between 90 and 119 days after
      biopsy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.01-1.18) and
      more than 119 days (HR, 1.12; 95% CI, 1.02-1.22) had a higher risk for mortality
      compared with those treated within 30 days of biopsy. In a subgroup analysis of
      stage I, higher mortality risk was found in patients treated within 30 to 59 days
      (HR, 1.05; 95% CI, 1.01-1.1), 60 to 89 days (HR, 1.16; 95% CI, 1.07-1.25), 90 to
      119 days (HR, 1.29; 95% CI, 1.12-1.48), and more than 119 days after biopsy (HR,
      1.41; 95% CI, 1.21-1.65). Surgical timing did not affect survival in stages II
      and III. LIMITATIONS: Melanoma-specific survival was not available. CONCLUSION:
      Expeditious treatment of stage I melanoma is associated with improved outcomes.

PMID- 29054720
TI  - A Randomized Comparison of 2 Robotic Virtual Reality Simulators and Evaluation of
      Trainees' Skills Transfer to a Simulated Robotic Urethrovesical Anastomosis Task.
AB  - OBJECTIVE: To determine, via a randomized comparison study, whether robotic
      simulator-acquired skills transfer to performance of a urethrovesical anastomosis
      (UVA) on a 3-dimensional-printed bladder model using the da Vinci Robot.
      MATERIALS AND METHODS: Medical students, surgical residents, and fellows were
      recruited and divided into 2 groups: Group 1 (G1) (junior trainees) and Group 2
      (G2) (senior trainees). Participants were randomized to identical simulator
      training curricula on the dV-Trainer (dV-T) or da Vinci Surgical Skills Simulator
      (dVSSS). Participants then completed a UVA task on a 3-dimensional-printed
      bladder model using the da Vinci robot. Three blinded expert robotic surgeons
      rated videotaped performances of the UVA task using validated assessment tools,
      namely, the Global Evaluative Assessment of Robotic Skills (GEARS; overall
      procedure) and Robotic Anastomosis Competence Evaluation (RACE; specific to UVA).
      RESULTS: Thirty-nine participants (G1 = 23 and G2 = 16) completed the study.
      Participants in G2 had significantly more simulation and surgical experience
      compared with G1 (P <.05). UVA scores of the dVSSS group were higher compared
      with dV-T (GEARS: P = .09; RACE: P = .01). In the G1 cohort, dVSSS scores were
      significantly higher than dV-T (GEARS: P = .01; RACE: P <.01). In the G2 cohort,
      scores were statistically similar (GEARS: P = .32; RACE: P = .91). CONCLUSION:
      Compared with the dV-T, the dVSSS training led to superior GEARS and RACE scores
      for performance of the UVA task in junior trainees, but not in senior trainees.
      The dVSSS can be used to improve surgical skills acquisition in less experienced
      trainees in a safe and effective manner.

PMID- 29054721
TI  - Characterizing the Association Between Toll-like Receptor Subtypes and
      Nephrolithiasis With Renal Inflammation in an Animal Model.
AB  - OBJECTIVE: To show experimentally induced renal stone disease and to evaluate
      secondary inflammatory responses in vivo, and to characterize changes in the
      expression of Toll-like receptor (TLR) subtypes in this model. METHODS: Twenty 5-
      to 6-week-old male Wistar rats were divided into control and hyperoxaluria groups
      (n = 10 per group) and were supplied with normal water or 1% ethylene glycol,
      respectively, for 16 weeks. The animals were then placed in metabolic cages, and
      urine was collected for a 24-hour urine oxalate level evaluation. Following
      sacrifice, rats were subjected to bilateral nephrectomy and both kidneys were
      histopathologically evaluated. A 1-mm3 biopsy section from the right kidney of
      each rat was subjected to real-time polymerase chain reaction of the TLR
      expression. RESULTS: At the end of week 16, the hyperoxaluria group had a higher
      mean 24-hour urine oxalate level (1.91) than the control group (0.29) (P <.05)
      and a remarkably increased deposition of renal CaOx crystals (15/20) than the
      control group (0/20) (P <.05), which was universally accompanied by inflammation
      (15/15). Twelve and no rats in the hyperoxaluria and control groups,
      respectively, had macroscopically visible renal pelvic stones (P <.05).
      Quantitative real-time polymerase chain reaction revealed significant decreases
      in the expression of several TLRs, particularly TLR11 and TLR7. Decreases in
      TLR1, TLR3, and TLR6 expressions and an increase in the TLR2 expression did not
      differ significantly between the groups. CONCLUSION: We believe that is the first
      evaluation of TLR expression associated with renal stone formation in an animal
      model of inflammation. These results might lead to novel TLR-based treatments for
      nephrolithiasis and related inflammatory renal damage.

PMID- 29054722
TI  - The eyelids and tear film in contact lens discomfort.
AB  - PURPOSE: To investigate characteristics of the eyelid margins, meibomian glands
      and the tear film of contact lens wearers, and to determine whether these
      characteristics were related to symptoms of contact lens discomfort. METHODS: A
      cross sectional study was performed on thirty existing daily wear soft contact
      lens wearers (6 male; 24 female) with median age of 23 years (range 18-41).
      Eyelid signs and tear film characteristics were evaluated during a single visit
      and subjects completed the contact lens and dry eye questionnaire (CLDEQ-8) to
      evaluate ocular discomfort. RESULTS: Based on the CLDEQ-8 responses, subjects
      were classified as symptomatic (n = 17) or asymptomatic (n = 13). Grades of foam
      at meibomian gland orifices (3 +/- 1), expressibility (2 +/- 1) and quality of
      secretions (2 +/- 1), tear evaporation rate with (112 +/- 54 g/m2/h) or without
      (88 +/- 45 g/m2/h) contact lens wear, fluorescein tear breakup time (8 +/- 2
      seconds) and tear lipid layer thickness (45 +/- 17 nm) were significantly
      associated with symptoms of discomfort in symptomatic lens wearers only (r2 >
      0.45; p value < 0.05). Upper lid-wiper epitheliopathy, meibomian gland acini
      reflectivity and tear meniscus height showed significant correlations with
      comfort scores in both symptomatic and asymptomatic contact lens wearers (p <
      0.05). A greater number of Demodex mites was also observed in the upper eyelid of
      symptomatic lens wearers (2 +/- 1) compared to asymptomatic lens wearers (0 +/-
      0; p value = 0.042). CONCLUSIONS: Morphological irregularities of the meibomian
      glands and alterations to tear film secretions that affect tear evaporative
      dynamics were associated with symptoms of discomfort amongst the symptomatic lens
      wearers.

PMID- 29054723
TI  - Aberrant frequency of IL-35 producing B cells in colorectal cancer patients.
AB  - BACKGROUND: The IL-10 dependent regulatory function of B cells had recently more
      and more investigated and play important roles in cancer immunity, however,
      beyond IL-10 whether other inhibitory cytokines play an important role in cancer
      is lacking. Here, we investigated the role of IL-35 producing B cells in
      colorectal cancer (CRC). METHODS: Thirty-two healthy controls (HC) and 49
      untreated CRC patients were enrolled and the IL-35 producing B cells in the
      peripheral blood were investigated. Additionally, CD4+CD25+/highCD127low/-
      regulatory T (Treg) and CD14+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs)
      were also investigated. RESULTS: Results show that IL-35 producing B cells were
      significantly upregulated during the clinical progression of CRC, and negatively
      correlated with CD3+ T cell, positively correlated with the frequency of
      CD4+CD25+/highCD127low/- Treg cells and CD14+HLA-DRlow/- MDSCs of these CRC
      patients. CONCLUSIONS: Together, IL-35 producing B cells were significantly
      elevated in CRC, indicating this B cell subset might participate in the immune
      suppression of CRC.

PMID- 29054724
TI  - Proinflammatory cytokine interferon-gamma increases the expression of BANCR, a
      long non-coding RNA, in retinal pigment epithelial cells.
AB  - The inflammatory response may contribute to retinal pigment epithelial (RPE)
      dysfunction associated with the pathogenesis of age-related macular degeneration
      (AMD). We investigated whether the inflammatory response affects the expression
      of long coding RNAs (lncRNAs) in human RPE-derived ARPE-19 cells. This class of
      regulatory RNA molecules recently came to prominence due to their involvement in
      many pathophysiological processes. A proinflammatory cytokine mixture consisting
      of IFN-gamma, IL-1beta and TNF-alpha altered the expression several lncRNAs
      including BANCR in these cells. The cytokine responsible for increasing BANCR
      expression in ARPE-19 cells was found to be IFN-gamma. BANCR expression induced
      by IFN-gamma was suppressed when STAT1 phosphorylation was blocked by JAK
      inhibitor 1. Thus, proinflammatory cytokines could modulate the expression of
      lncRNAs in RPE cells and IFN-gamma could upregulate the expression of BANCR by
      activating JAK-STAT1 signaling pathway.

PMID- 29054725
TI  - Accelerometer-Based and Computer-Assisted Navigation in Total Knee Arthroplasty:
      A Reduction in Mechanical Axis Outliers Does Not Lead to Improvement in
      Functional Outcomes or Quality of Life When Compared to Conventional Total Knee
      Arthroplasty.
AB  - BACKGROUND: Accelerometer-based navigation (ABN) is a novel navigation system
      that attempts to combine the accuracy of computer-assisted surgery (CAS) with the
      familiarity of conventional instrumentation (CON). No studies have compared the
      clinical outcomes of this new technology with existing techniques to date.
      METHODS: From July 2013 to April 2014, 152 consecutive patients (152 knees)
      underwent total knee arthroplasty using ABN (n = 38), CAS (n = 38), or CON (n =
      76). We prospectively matched the groups in a 1:1:2 ratio for age, gender, body
      mass index, preoperative range of motion, Knee Society Score, Oxford Knee Score,
      Short-Form 36 Physical and Mental Component Scores, and preoperative deformity
      using preoperative data in isolation, thus controlling for potential confounding
      factors. All patients were prospectively followed for 2 years. RESULTS: The ABN
      and CAS groups had a significantly improved mean mechanical axis (P = .018),
      femoral (P = .050) and tibial component alignment (P = .008) compared to the CON
      group. There were significantly less mechanical axis outliers in the ABN and CAS
      groups (P = .034). The duration of surgery for the ABN group (83.9 +/- 21 min)
      was significantly shorter than the CAS group (101 +/- 11 min; P < .001) but
      similar to the CON group (76.6 +/- 17 min; P = .131). There was no significant
      difference in functional outcomes, quality of life measures or satisfaction rates
      between the 3 groups at 2 years (P > .05). CONCLUSION: Although bone cuts were as
      accurate as CAS and operation time was similar to CON, the use of ABN failed to
      demonstrate any advantages in clinical outcomes following total knee arthroplasty
      at 2 years follow-up.

PMID- 29054726
TI  - A Comparison of Walking Gait Following Mechanical and Kinematic Alignment in
      Total Knee Joint Replacement.
AB  - BACKGROUND: Although previous studies have compared radiological, pain, and
      function scores in kinematically aligned (KA) and mechanically aligned (MA) total
      knee arthroplasty (TKA), no previous studies have undertaken a three-dimensional
      (3D) gait analysis in these groups. This study compared kinematic and kinetic
      variables recorded during level walking in patients at least 2 years post-surgery
      who underwent an MA or KA procedure. METHODS: Utilizing a 9-camera motion
      analysis system, gait analysis was undertaken on 29 patients (MA = 15, KA = 14).
      A 9-camera motion analysis system was used to collect 3D kinematic data of the
      involved and uninvolved limbs during walking at a self-selected speed.
      Additionally, 3D ground reaction forces and moments during the stance phase were
      recorded, and an inverse dynamics approach was utilized to analyze these data.
      RESULTS: There were no significant differences in spatial-temporal variables
      between MA and KA groups (P > .05). Local minima and maxima for knee joint angles
      were not significantly different (P > .05) across involved and uninvolved legs
      and MA/KA groups in any of the 3 planes of motion. Principal component analysis
      revealed a significant difference (P < .05) in the transverse plane moment in
      late stance. No other significant differences were observed for knee, hip, or
      ankle joint moments. CONCLUSION: Differences in gait parameters across the KA and
      MA groups at 2 years post-surgery were insufficient to support either one of the
      operative procedures over the other.

PMID- 29054727
TI  - Evaluation of immune responses in dogs to oral rabies vaccine under field
      conditions.
AB  - During the 20th century parenteral vaccination of dogs at central-point locations
      was the foundation of successful canine rabies elimination programs in numerous
      countries. However, countries that remain enzootic for canine rabies have lower
      infrastructural development compared to countries that have achieved elimination,
      which may make traditional vaccination methods less successful. Alternative
      vaccination methods for dogs must be considered, such as oral rabies vaccine
      (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was
      supplemented with ORV to improve vaccination coverage and to evaluate the use of
      ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were
      placed in intestine bait and distributed to dogs by hand. Serum was collected
      from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre
      vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid
      florescent focus inhibition test (RFFIT) was used to detect neutralizing
      antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination,
      38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody
      (RFFIT >0.05 IU/mL), compared to 16/27 (59.3%, p < 0.01) dogs that received ORV
      or 21/27 (77.8%) as measured by ELISA (>40% blocking, p < 0.05). The fate of 291
      oral vaccines was recorded; 283 dogs (97.2%) consumed the bait; 272 dogs (93.4%)
      were observed to puncture the blister, and only 14 blisters (4.8%) could not be
      retrieved by vaccinators and were potentially left in the environment. Pre
      vaccination antibodies (RFFIT >0.05 IU/mL) were detected in 10/107 reportedly
      vaccine-naive dogs (9.3%). Parenteral vaccination remains the most reliable
      method for ensuring adequate immune response in dogs, however ORV represents a
      viable strategy to supplement existing parental vaccination campaigns in hard-to
      reach dog populations. The hand-out model reduces the risk of unintended contact
      with ORV through minimizing vaccine blisters left in the community.

PMID- 29054728
TI  - A novel multi-variant epitope ensemble vaccine against avian leukosis virus
      subgroup J.
AB  - The hypervariable antigenicity and immunosuppressive features of avian leukosis
      virus subgroup J (ALV-J) has led to great challenges to develop effective
      vaccines. Epitope vaccine will be a perspective trend. Previously, we identified
      a variant antigenic neutralizing epitope in hypervariable region 1 (hr1) of ALV
      J, N-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-C. BLAST analysis showed that the mutation of
      A, E, T and H in this epitope cover 79% of all ALV-J strains. Base on this data,
      we designed a multi-variant epitope ensemble vaccine comprising the four mutation
      variants linked with glycine and serine. The recombinant multi-variant epitope
      gene was expressed in Escherichia coli BL21. The expressed protein of the variant
      multi-variant epitope gene can react with positive sera and monoclonal antibodies
      of ALV-J, while cannot react with ALV-J negative sera. The multi-variant epitope
      vaccine that conjugated Freund's adjuvant complete/incomplete showed high
      immunogenicity that reached the titer of 1:64,000 at 42 days post immunization
      and maintained the immune period for at least 126 days in SPF chickens. Further,
      we demonstrated that the antibody induced by the variant multi-variant ensemble
      epitope vaccine recognized and neutralized different ALV-J strains (NX0101, TA1,
      WS1, BZ1224 and BZ4). Protection experiment that was evaluated by clinical
      symptom, viral shedding, weight gain, gross and histopathology showed 100%
      chickens that inoculated the multi-epitope vaccine were well protected against
      ALV-J challenge. The result shows a promising multi-variant epitope ensemble
      vaccine against hypervariable viruses in animals.

PMID- 29054729
TI  - Hib antibody responses in infants following diphtheria, tetanus, acellular
      pertussis, and conjugated Haemophilus influenzae type b (Hib) combination
      vaccines with decreasing amounts of tetanus toxoid.
AB  - BACKGROUND: While combination vaccines have contributed to improved vaccine
      uptake rates in children, studies have documented varied immunogenicity to
      specific vaccine components. We studied whether varying the amount of tetanus
      toxoid (TT) in a DTaP and Hib combination vaccine would result in immunogenicity
      comparable with separate, concurrent administration. METHODS: We evaluated the
      immunogenicity of Massachusetts Biologic Laboratories (MBL) diphtheria, tetanus,
      and acellular pertussis (mDTaP) vaccine combined with tetanus-conjugated MBL
      Haemophilus influenzae type b vaccine (mHib) in a single injection (DTaPH). We
      compared four DTaPH vaccines containing varying concentrations of TT. We also
      evaluated the immune response to the DTaP vaccine manufactured by Connaught
      Laboratories (now known as Sanofi Pasteur) given with mHib and with Wyeth Hib
      CRM197 (HbOC) as separate injections. Vaccines were administered to 240 healthy
      infants at 2, 4, and 6 months of age, and blood specimens for antibody
      determination were obtained before each immunization and one month after the
      third immunization. RESULTS: We found no significant differences in immune
      response to the vaccines between the four DTaPH groups. Hib antibody responses
      were similar in the mHib and the HbOC groups but significantly lower in the DTaPH
      groups, as measured by Chinese Hamster Ovary (CHO) cell neutralization titers and
      filamentous hemagglutinin antigen (FHA) geometric mean concentrations (GMC) of
      anti-Hib antibodies. There were no significant differences between the groups in
      pertussis or tetanus toxoid antibody levels. CONCLUSION: Reducing tetanus toxoid
      amounts did not produce comparable immunogenicity for Hib. The nature of the
      interaction between immune responses to DTaPH components should be explored
      further to enable the development of better Hib-containing combination vaccines.

PMID- 29054730
TI  - The translocator protein (18kDa) and its role in neuropsychiatric disorders.
AB  - Translocator protein (TSPO) is an 18kDa translocator membrane protein expressed
      in the outer mitochondrial membrane of steroid-synthesizing cells in the central
      and peripheral nervous systems. TSPO is involved in cellular functions, including
      the regulation of cell proliferation, transport of cholesterol to the inner
      mitochondrial membranes of glial cells, regulation of mitochondrial quality
      control, and haem synthesis. In the brain, TSPO has been extensively used as a
      biomarker of injury and inflammation. Indeed, TSPO was up-regulated in several
      inflammatory and neurodegenerative diseases. In contrast, the expression of TSPO
      was decreased in peripheral blood from psychiatric patients. Since TSPO is
      involved in several mechanisms related to mitochondrial function and inflammatory
      alterations, therapeutic approaches focusing on the regulation of TSPO may
      provide a new avenue for the treatment of neuropsychiatric disorders. Based on
      the involvement of mitochondrial alterations in the neurobiology of
      neuropsychiatric disorders, this review will focus on the functions and
      physiological roles of TSPO and the potential of TSPO ligands as therapeutic
      strategies for the treatment of neuropsychiatric disorders.

PMID- 29054731
TI  - The impact of obesity and hypercaloric diet consumption on anxiety and emotional
      behavior across the lifespan.
AB  - Obesity is an increasing problem in young people. Childhood obesity and
      overweight have increased rapidly on a global scale, and have tripled in the past
      30 years, to affect approximately one in five children. Diets high in refined
      fats and sugar are a major contributor to the development of obesity, and the
      effects of such obesity-inducing hypercaloric diets on brain function may
      contribute to the high prevalence of anxiety disorders in people with obesity.
      Anxiety disorders typically emerge in childhood and adolescence, and symptoms
      often continue into adulthood. Based on this symptomology, we consider anxiety
      related behavioral consequences of hypercaloric diets across development. We
      review research on the effects of hypercaloric dietary manipulations across the
      lifespan on emotion regulation and the neurobiological mechanisms that underpin
      these processes. Cumulatively, the findings reveal that gestation and the
      juvenile/adolescent developmental periods may be early-life windows of
      vulnerability for developing anxiety in later life due to the augmented effects
      of these diets on neuroendocrine stress systems and the maturation of neural
      circuitry supporting emotion regulation.

PMID- 29054732
TI  - Factual Inaccuracies Contained in the Article Entitled "Low Yield of Mobile
      Cardiac Outpatient Telemetry after Cryptogenic Stroke in Patients with Extensive
      Cardiac Imaging".

PMID- 29054733
TI  - Disrupted Ionic Homeostasis in Ischemic Stroke and New Therapeutic Targets.
AB  - BACKGROUND: Stroke is a leading cause of long-term disability. All
      neuroprotectants targeting excitotoxicity have failed to become stroke
      medications. In order to explore and identify new therapeutic targets for stroke,
      we here reviewed present studies of ionic transporters and channels that are
      involved in ischemic brain damage. METHOD: We surveyed recent literature from
      animal experiments and clinical reports in the databases of PubMed and Elsevier
      ScienceDirect to analyze ionic mechanisms underlying ischemic cell damage and
      suggest promising ideas for stroke therapy. RESULTS: Dysfunction of ionic
      transporters and disrupted ionic homeostasis are most early changes that underlie
      ischemic brain injury, thus receiving sustained attention in translational stroke
      research. The Na+/K+-ATPase, Na+/Ca2+ Exchanger, ionotropic glutamate receptor,
      acid-sensing ion channels (ASICs), sulfonylurea receptor isoform 1 (SUR1)
      regulated NCCa-ATP channels, and transient receptor potential (TRP) channels are
      critically involved in ischemia-induced cellular degenerating processes such as
      cytotoxic edema, excitotoxicity, necrosis, apoptosis, and autophagic cell death.
      Some ionic transporters/channels also act as signalosomes to regulate cell death
      signaling. For acute stroke treatment, glutamate-mediated excitotoxicity must be
      interfered within 2 hours after stroke. The SUR1-regulated NCCa-ATP channels,
      Na+/K+-ATPase, ASICs, and TRP channels have a much longer therapeutic window,
      providing new therapeutic targets for developing feasible pharmacological
      treatments toward acute ischemic stroke. CONCLUSION: The next generation of
      stroke therapy can apply a polypharmacology strategy for which drugs are designed
      to target multiple ion transporters/channels or their interaction with neurotoxic
      signaling pathways. But a successful translation of neuroprotectants relies on in
      depth analyses of cell death mechanisms and suitable animal models resembling
      human stroke.

PMID- 29054734
TI  - Computer-Facilitated Screening and Brief Advice to Reduce Adolescents' Heavy
      Episodic Drinking: A Study in Two Countries.
AB  - PURPOSE: A computer-facilitated screening and brief advice (cSBA) intervention
      was previously shown to reduce drinking among U.S. adolescents but not among
      Czech youth. The purpose of this study was to assess cSBA effect on heavy
      episodic drinking (HED). METHODS: Participants were 12- to 18-year-olds at nine
      U.S. primary care offices (N = 2,096) and 10 Czech pediatrician-generalist
      offices (N = 589) who completed measurements only during an 18-month treatment-as
      usual (TAU) phase. We then initiated the cSBA protocol for all participants and
      recruited the 18-month cSBA phase. Generalized Estimating Equations logistic
      regression compared past-90-day HED for cSBA versus TAU at 3- and 12-months,
      controlling for baseline HED and other covariates. RESULTS: Baseline past-90-day
      HED rates were 11% for U.S. and 28% for Czech youth. At 3 months, among Czech
      baseline non-HED, the adjusted relative risk ratio for cSBA versus TAU was .52
      (95% confidence interval .29, .92). The effect dissipated by 12 months.
      CONCLUSIONS: cSBA shows promise for short-term prevention of adolescent HED.

PMID- 29054736
TI  - Bidirectional Associations Between Adolescents' Sexual Behaviors and
      Psychological Well-Being.
AB  - PURPOSE: Assessing bidirectional longitudinal associations between early sexual
      behaviors (<=16.0 years) and psychological well-being (global self-esteem,
      physical self-esteem, depression) among 716 adolescents, and the direct and
      buffering effect of parent-adolescent relationship quality. METHODS: We used data
      from Project STARS (Studies on Trajectories of Adolescent Relationships and
      Sexuality), a longitudinal study on adolescent sexual development in the
      Netherlands. Participants were 11.0-16.0 years old (mean age at T1 = 13.3 years).
      Self-reports from four waves of online questionnaires were used. Bidirectional
      longitudinal associations were assessed by linear mixed-effects models. RESULTS:
      At most waves, boys had significantly higher levels of psychological well-being
      than girls, but genders did not differ in experience with sexual behaviors.
      Engagement in early sexual behaviors did not predict lower levels of
      psychological well-being over time, and lower levels of psychological well-being
      did not predict more engagement in early sexual behaviors over time. Parent
      adolescent relationship quality did not moderate these associations in either
      direction, although we found a significant direct effect, in which a higher
      quality parent-adolescent relationship predicted more optimal levels of the three
      indicators of adolescents' psychological well-being (but not lower levels of
      early sexual activity) over time. CONCLUSIONS: Our results show that, among Dutch
      adolescents, early sexual behaviors and psychological well-being were not
      interrelated. This may be explained by socio-cultural aspects of the Dutch
      society, such as more normalization of sexual behaviors during adolescence. As a
      result, early sexual activity in and of itself was not related to lower
      psychological well-being over time. Yet, cross-cultural differences in links
      between adolescents' sexuality and well-being should be further investigated.

PMID- 29054735
TI  - Associations Between Neural Reward Processing and Binge Eating Among Adolescent
      Girls.
AB  - PURPOSE: Neuroimaging studies suggest that altered brain responses to food
      related cues in reward-sensitive regions characterize individuals who experience
      binge-eating episodes. However, the absence of longitudinal data limits the
      understanding of whether reward-system alterations increase vulnerability to
      binge eating, as theorized in models of the development of this behavior.
      METHODS: Adolescent girls (N = 122) completed a functional magnetic resonance
      imaging monetary reward task at age 16 years as part of an ongoing longitudinal
      study. Self-report of binge eating was assessed using the Eating Attitudes Test
      at ages 16 and 18 years. Regression analyses examined concurrent and longitudinal
      associations between the blood-oxygenation-level-dependent response to
      anticipating and winning monetary rewards and the severity of binge eating while
      controlling for age 16 depressive symptoms and socioeconomic status. RESULTS:
      Greater ventromedial prefrontal cortex and caudate responses to winning money
      were correlated with greater severity of binge eating concurrently but not
      prospectively. CONCLUSIONS: This study is the first to examine longitudinal
      associations between reward responding and binge eating in community-based,
      mostly low-socioeconomic status adolescent girls. Ventromedial prefrontal cortex
      response to reward outcome-possibly reflecting an enhanced subjective reward
      value-appears to be a state marker of binge-eating severity rather than a
      predictor of future severity.

PMID- 29054737
TI  - A novel DTI-QA tool: Automated metric extraction exploiting the sphericity of an
      agar filled phantom.
AB  - PURPOSE: To develop a quality assurance (QA) tool (acquisition guidelines and
      automated processing) for diffusion tensor imaging (DTI) data using a common agar
      based phantom used for fMRI QA. The goal is to produce a comprehensive set of
      automated, sensitive and robust QA metrics. METHODS: A readily available agar
      phantom was scanned with and without parallel imaging reconstruction. Other
      scanning parameters were matched to the human scans. A central slab made up of
      either a thick slice or an average of a few slices, was extracted and all
      processing was performed on that image. The proposed QA relies on the creation of
      two ROIs for processing: (i) a preset central circular region of interest (ccROI)
      and (ii) a signal mask for all images in the dataset. The ccROI enables
      computation of average signal for SNR calculations as well as average FA values.
      The production of the signal masks enables automated measurements of eddy current
      and B0 inhomogeneity induced distortions by exploiting the sphericity of the
      phantom. Also, the signal masks allow automated background localization to assess
      levels of Nyquist ghosting. RESULTS: The proposed DTI-QA was shown to produce
      eleven metrics which are robust yet sensitive to image quality changes within
      site and differences across sites. It can be performed in a reasonable amount of
      scan time (~15min) and the code for automated processing has been made publicly
      available. CONCLUSIONS: A novel DTI-QA tool has been proposed. It has been
      applied successfully on data from several scanners/platforms. The novelty lies in
      the exploitation of the sphericity of the phantom for distortion measurements.
      Other novel contributions are: the computation of an SNR value per gradient
      direction for the diffusion weighted images (DWIs) and an SNR value per non-DWI,
      an automated background detection for the Nyquist ghosting measurement and an
      error metric reflecting the contribution of EPI instability to the eddy current
      induced shape changes observed for DWIs.

PMID- 29054738
TI  - Impact of body constitution on complications following pancreaticoduodenectomy: A
      retrospective cohort study.
AB  - BACKGROUND: Overweight, defined by body mass index (BMI), is correlated to
      complications following pancreaticoduodenectomy (PD). The aim of this study was
      to evaluate the impact of body constitution, measured with different
      anthropometric measures, and diabetes on complications following PD. MATERIALS
      AND METHODS: Patients who underwent PD between 2000 and 2015 at Skane University
      Hospital were retrospectively included. Body mass index (BMI), body surface area
      (BSA) and body fat percentage (BF%) were calculated. Overweight and obesity were
      defined by BMI according to the WHO classification (overweight >=25 and obesity
      >=30). Values equal to or above the median value were considered as large by BSA
      (>=1.87) and overweight by BF% (>=29.6% (male) and >=38.9% (female)). Main
      endpoints were events of postoperative pancreatic fistula (POPF), post
      pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE) and complications
      classified according to the Clavien-Dindo classification. Multivariable analysis
      was performed using logistic regression and a subgroup analysis on diabetic
      patients was performed. RESULTS: In total 328 patients were included. The
      incidence of POPF grades B and C was increased among overweight and large
      patients defined by BMI (OR 4.16; p = 0.001), BSA (OR 2.88; p = 0.018) and BF%
      (OR 3.94; p = 0.001). However, the risk was not increased among diabetic patients
      with BMI>=25 and BMI>=30. DGE and complications classified as Clavien grade >=3
      were more common in patients defined as overweight by both BMI (OR 1.72; p =
      0.024 and OR 2.63; p = 0.003, respectively) and BF% (OR 2.13; p = 0.001 and OR
      2.31; p = 0.009, respectively). PPH was not more frequent in overweight or large
      patients. CONCLUSION: Body constitution has an impact on the risk of severe
      complications following PD. BMI, BSA and BF% can all be used to identify risk
      groups. The risk of developing POPF grades B and C was significantly increased in
      overweight and large patients, but not in patients with coexisting diabetes.

PMID- 29054739
TI  - Engagement and role of surgical trainees in global surgery: Consensus statement
      and recommendations from the Association of Surgeons in Training.
AB  - BACKGROUND: There is a wide chasm in access to essential and emergency surgery
      between high and low/middle income countries (LMICs). Surgeons worldwide are
      integral to solutions needed to address this imbalance. Involving surgical
      trainees, who represent the future of surgery, is vital to this endeavour. The
      Association of Surgeons in Training (ASiT) is an independent charity that support
      surgical trainees of all ten surgical specialties in the UK and Ireland. ASiT
      convened a consensus meeting at the ASiT conference in Liverpool 2016 to discuss
      trainee engagement with global surgery, including potential barriers and
      solutions. METHODS: A face-to-face consensus meeting reviewed the engagement of,
      and roles for, surgical trainees in global surgery at the ASiT Conference
      (Liverpool, England), March 2016. Participants self-identified based on
      experience and interest in the field, and included trainees (residents and
      students) and consultants (attending grade). Following expert review, seven pre
      determined core areas were presented for review and debate. Extensive discussion
      was facilitated by a consultant and a senior surgical trainee, with expertise in
      global surgery. The draft derived from these initial discussions was circulated
      to all those who had participated, and an iterative process of revision was
      undertaken until a final consensus and recommendations were reached. RESULTS:
      There is increasing interest from trainee surgeons to work in LMICs. There are
      however, ethical considerations, and it is important that trainees working in
      LMICs undertake work appropriate to their training stage and competencies.
      Visiting surgeons must consider the requirements of the hosting centres rather
      than just their own objectives. If appropriately organised, both short and long
      term visits, can enable development of transferable clinical, organisational,
      research and education skills. A central repository of information on global
      surgery would be useful to trainees, to complement existing resources. Challenges
      to trainees considering a global surgery placement include approval for
      placements while on a training program, financial cost and dangers inherent in
      working in a resource poor setting. Currently global surgery experience is
      generally as an out of program experience and does not count for certificate of
      completion of training (CCT). Methods to recognise surgical trainee global
      surgery experience as an integrated part of training should be explored, similar
      to that seen in other specialties. CONCLUSION: There is a role for surgical
      trainees to become involved in Global Surgery, especially in partnership with
      local surgeons and with appropriate ethical consideration. Trainees develop
      translational skills in resource poor settings. Development of appropriate
      pathways for recognition of global surgery experience for CCT should be
      considered.

PMID- 29054740
TI  - Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and
      oxidative stress.
AB  - Acute lung injury (ALI) is a common severe clinical syndrome in intensive care
      unit. Inflammation has been reported to play a critical role in the development
      of ALI. Cordycepin, an active component isolated from Cordyceps militaris, has
      been reported to have anti-inflammatory effects. However, the anti-inflammatory
      effects of cordycepin on LPS-induced ALI remain unclear. Therefore, in the
      present study, we assessed whether cordycepin could attenuate ALI induced by LPS.
      The mice were conditioned with cordycepin 1h before intranasal instillation of
      LPS. Lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory
      cytokines production were detected. The expression of NF-kappaB p65, I-kappaB,
      Nrf2, and HO-1 were detected by western blot analysis. We found that LPS
      significantly increased lung wet/dry (W/D) ratio, MPO activity, MDA content, and
      inflammatory cytokines production. However, the increases were significantly
      inhibited by treatment of cordycepin. LPS-induced NF-kappaB activation was also
      suppressed by cordycepin. In addition, cordycepin was found to up-regulate the
      expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, our
      results demonstrated that cordycepin could attenuate LPS-induced ALI effectively,
      probably due to inhibition of inflammation and oxidative stress.

PMID- 29054741
TI  - Virucidal efficacy of food additive grade calcium hydroxide against surrogate of
      human norovirus.
AB  - An alkaline agent, namely, food additive grade calcium hydroxide (FdCa(OH)2) in
      the solution, powder and suspension forms was evaluated as a virucidal agent,
      using a murine norovirus (MNV) as the surrogate for human norovirus. The main
      constituent of FdCa(OH)2 is Ca(OH)2, which has pH 13 in 0.17% solution. The
      results showed that 0.17% FdCa(OH)2 solution could inactivate MNV within 30s even
      in the presence of organic materials (5% fetal bovine serum (FBS)). In a
      contaminated surface experiment, MNV with 5% FBS was inoculated on rayon sheets,
      and the result showed FdCa(OH)2 solution could markedly reduce virus titer within
      1min. When mouse feces were spiked with MNV and FdCa(OH)2 powder as 10% and 20%
      w/w was added to the feces, these concentrations could inactivate the virus
      within 30min and 15min, respectively. Whereas, FdCa(OH)2 suspension at 2.5% and
      5% could inactivate the virus within 30min and at 1% within 45min. These and
      additional results obtained here indicate that FdCa(OH)2 is an effective
      virucidal agent against MNV, and can serve as a useful alternative disinfectant
      for inactivation and prevention of human norovirus in house and hospital.

PMID- 29054742
TI  - Failing to pay heed to health warnings in a food-associated environment.
AB  - People often fail to adhere to food-related health information. Increasing
      evidence suggests that environmental stimuli interfere with good intentions by
      triggering choices relatively automatically. Using a Pavlovian-instrumental
      transfer (PIT) task, we examined whether food-associated stimuli reduce health
      warnings' effectiveness. We expected that people adhere to health warnings in the
      absence, but not presence, of food-associated stimuli. In addition, we examined
      timing effects, i.e., whether health warnings are more effective when they are
      given prior to associative learning rather than afterwards. In the PIT task,
      participants learned to press keys for two food rewards (instrumental learning)
      and associations between stimuli and these rewards (Pavlovian learning) in
      separated phases. Health warnings about one reward were given after associative
      learning (Study 1), or before versus afterwards (Study 2). During test phase,
      participants pressed for food outcomes while occasionally food-related stimuli
      were presented. In absence of food-related stimuli, participants increased
      responding for rewards perceived as more healthy. However, when stimuli were
      present, responding was biased towards the signaled outcome, regardless of health
      warnings or timing. Health messages influence food choice behavior, but are no
      longer effective when food-associated stimuli are present. This provides
      important insights why health warning effects might be limited in an obesogenic
      environment.

PMID- 29054743
TI  - Simultaneous RNA-seq based transcriptional profiling of intracellular Brucella
      abortus and B. abortus-infected murine macrophages.
AB  - Brucella is a zoonotic pathogen that survives within macrophages; however the
      replicative mechanisms involved are not fully understood. We describe the
      isolation of sufficient Brucella abortus RNA from primary host cell environment
      using modified reported methods for RNA-seq analysis, and simultaneously
      characterize the transcriptional profiles of intracellular B. abortus and bone
      marrow-derived macrophages (BMM) from BALB/c mice at 24 h (replicative phase)
      post-infection. Our results revealed that 25.12% (801/3190) and 16.16% (515/3190)
      of the total B. abortus genes were up-regulated and down-regulated at >2-fold,
      respectively as compared to the free-living B. abortus. Among >5-fold
      differentially expressed genes, the up-regulated genes are mostly involved in
      DNA, RNA manipulations as well as protein biosynthesis and secretion while the
      down-regulated genes are mainly involved in energy production and metabolism. On
      the other hand, the host responses during B. abortus infection revealed that
      14.01% (6071/43,346) of BMM genes were reproducibly transcribed at >5-fold during
      infection. Transcription of cytokines, chemokines and transcriptional factors,
      such as tumor necrosis factor (Tnf), interleukin-1alpha (Il1alpha), interleukin
      1beta (Il1beta), interleukin-6 (Il6), interleukin-12 (Il12), chemokine C-X-C
      motif (CXCL) family, nuclear factor kappa B (Nf-kappab), signal transducer and
      activator of transcription 1 (Stat1), that may contribute to host defense were
      markedly induced while transcription of various genes involved in cell
      proliferation and metabolism were suppressed upon B. abortus infection. In
      conclusion, these data suggest that Brucella modulates gene expression in hostile
      intracellular environment while simultaneously alters the host pathways that may
      lead to the pathogen's intracellular survival and infection.

PMID- 29054744
TI  - Sternal manubriotomy for mediastinal goiter.

PMID- 29054745
TI  - Lower limb injuries in men's elite Gaelic football: A prospective investigation
      among division one teams from 2008 to 2015.
AB  - OBJECTIVES: To prospectively investigate incidence and associated time-loss of
      lower limb injuries in elite Gaelic football. Additionally, to identify sub
      groups of elite players at increased risk of sustaining a lower limb injury.
      DESIGN: Prospective, epidemiological study. METHODS: Team physiotherapists
      provided exposure and injury on a weekly basis to the National Gaelic Athletic
      Association (GAA) Injury Surveillance Database. Injury was defined using a time
      loss criterion. Fifteen different teams participated throughout the 8-year study
      providing 36 team datasets from 2008 to 2015. RESULTS: Lower limb injuries
      (n=1239) accounted for 83.5% (95% CI 82.0-85.0) and 77.6% (95% CI 75.8-79.4) of
      training and match-play injuries, respectively. Injury incidence was 4.5 (95% CI
      3.7-5.2) and 38.4 (95% CI 34.3-42.60) per 1000 training and match-play hours,
      respectively. One-in-four (25.0%, 95% CI 22.4-27.0) lower limb injuries were
      recurrent. Non-contact injuries accounted for 80.9% (95% CI 79.2-82.6) of cases.
      The median team rate was 30 (IQR 24-43) lower limb injuries per season resulting
      in 840.8 (95% CI 773.3-908.2) time-loss days. Previously injured players had a
      2.5-times (OR 95% CI 2.2-2.8) greater risk of sustaining a lower limb injury.
      Overall, 56.8% of players with a previous lower limb injury sustained another.
      Incidence was higher for forward players and those aged >25years. CONCLUSIONS:
      Lower limb injuries are the most common injury among elite division one Gaelic
      football teams. Injury risk management should become an ongoing component of a
      player's development programme and consider injury history, age, and playing
      position.

PMID- 29054747
TI  - U.S. Army physical demands study: Identification and validation of the physically
      demanding tasks of combat arms occupations.
AB  - OBJECTIVES: In 2013, the U.S. Army began developing physical tests to predict a
      recruit's ability to perform the critical, physically demanding tasks (CPDTs) of
      combat arms jobs previously not open to women. The purpose of this paper is to
      describe the methodology and results of analyses of the accuracy and
      inclusiveness of the critical physically demanding task list. While the job
      analysis included seven combat arms jobs, only data from the 19D Cavalry Scout
      occupation are presented as the process was similar for all seven jobs. DESIGN:
      Job analysis METHODS: As the foundation, senior subject matter experts from each
      job reviewed materials and reached consensus on the CPDTs and performance
      standards for each job. The list was reviewed by Army leadership and provided to
      the researchers. The job analysis consisted of reviewing job and task related
      documents and field manuals, observing >900 soldiers performing the 32 CPDTs,
      conducting two focus groups for each job, and analyzing responses to widely
      distributed job analysis questionnaires. RESULTS: Of the 32 CPDTs identified for
      seven combat jobs, nine were relevant to 19D soldiers. Focus group discussions
      and job analysis questionnaire results supported the tasks and standards
      identified by subject matter experts while also identifying additional tasks.
      CONCLUSIONS: The tasks identified by subject matter experts were representative
      of the physically demanding aspects of the 19D occupation.

PMID- 29054746
TI  - The influence of cadence and shoes on patellofemoral joint kinetics in runners
      with patellofemoral pain.
AB  - OBJECTIVES: To determine the effect of a combination of a minimalist shoe and
      increased cadence on measures of patellofemoral joint loading during running in
      individuals with patellofemoral pain. DESIGN: Within-participant repeated
      measures with four conditions presented in random order: (1) control shoe at
      preferred cadence; (2) control shoe with +10% cadence; (3) minimalist shoe at
      preferred cadence; (4) minimalist shoe with +10% cadence. METHODS: Fifteen
      recreational runners with patellofemoral pain ran on an instrumented treadmill
      while three-dimensional motion capture data were acquired. Peak patellofemoral
      joint stress, joint reaction force, knee extensor moment and knee joint angle
      during the stance phase of running were calculated. One-way repeated measures
      ANOVA was used to compare the control condition (1) to the three experimental
      conditions (2-4). RESULTS: Running in a minimalist shoe at an increased cadence
      reduced patellofemoral stress and joint reaction force on average by
      approximately 29% (p<0.001) compared to the control condition. Running in a
      minimalist shoe at preferred cadence reduced patellofemoral joint stress by 15%
      and joint reaction force by 17% (p<0.001), compared to the control condition.
      Running in control shoes at an increased cadence reduced patellofemoral joint
      stress and joint reaction force by 16% and 19% (p<0.001), respectively, compared
      to the control condition. CONCLUSIONS: In individuals with patellofemoral pain,
      running in a minimalist shoe at an increased cadence had the greatest reduction
      in patellofemoral joint loading compared to a control shoe at preferred cadence.
      This may be an effective intervention to modulate biomechanical factors related
      to patellofemoral pain.

PMID- 29054748
TI  - Effects of physical activity on executive functions, attention and academic
      performance in preadolescent children: a meta-analysis.
AB  - OBJECTIVES: The aim of this meta-analysis was to provide a systematic review of
      intervention studies that investigated the effects of physical activity on
      multiple domains of executive functions, attention and academic performance in
      preadolescent children (6-12 years of age). In addition, a systematic
      quantification of the effects of physical activity on these domains is provided.
      DESIGN: Systematic review and meta-analysis. METHODS: Searches of electronic
      databases and examining relevant reviews between 2000 and April 2017 resulted in
      31 intervention studies meeting the inclusion criteria. Four subdomains of
      executive functions (inhibition, working memory, cognitive flexibility and
      planning), three subdomains of attention (selective, divided and sustained) and
      three subdomains of academic performance (mathematics, spelling and reading) were
      distinguished. Effects for different study designs (acute physical activity or
      longitudinal physical activity programs), type of physical activity (aerobic or
      cognitively engaging) and duration of intervention were examined separately.
      RESULTS: Acute physical activity has a positive effect on attention (g=0.43; 95%
      CI=0.09, 0.77; 6 studies), while longitudinal physical activity programs has a
      positive effect on executive functions (g=0.24; 95% CI=0.09, 0.39; 12 studies),
      attention (g=0.90; 95% CI=0.56, 1.24; 1 study) and academic performance (g=0.26;
      95% CI=0.02, 0.49; 3 studies). The effects did depend on the subdomain.
      CONCLUSIONS: Positive effects were found for physical activity on executive
      functions, attention and academic performance in preadolescent children. Largest
      effects are expected for interventions that aim for continuous regular physical
      activity over several weeks.

PMID- 29054749
TI  - Men with unilateral Achilles tendinopathy have impaired balance on the
      symptomatic side.
AB  - OBJECTIVES: To investigate single leg standing balance in males with mid-portion
      Achilles tendinopathy (AT). DESIGN: Cross sectional case study. METHODS: Centre
      of pressure (COP) path length was measured using a Wii Balance Board (WBB) in 21
      male participants (20-60 years) with unilateral mid-portion AT during single-limb
      standing on each limb with eyes open and closed. Ultrasound imaging of both
      Achilles tendons was also performed by one blinded assessor, and the
      anteroposterior (AP) thickness and presence of pathology was determined.
      Comparisons were made between symptomatic and asymptomatic sides for key
      outcomes, and correlation between COP path length and variables of interest were
      investigated. RESULTS: Symptomatic Achilles tendons demonstrated significantly
      increased AP tendon thickness (p<0.001). Participants with AT demonstrated
      increased COP path length (sway amplitude) on their affected side during the eyes
      closed task (p=0.001). Increased tendon thickness was associated with increased
      sway amplitude during the eyes open task on both the affected (rho=0.44, p=0.045)
      and unaffected sides (rho=0.62, p=0.003). CONCLUSIONS: In males with AT, single
      leg standing balance with eyes closed is impaired on the symptomatic side. This
      indicates that neuromuscular deficits affecting functional ability may be present
      in people with AT during more challenging balance activities. It is unclear if
      this deficit precedes the onset of symptoms, or is a consequence of tendon pain.
      Work is now needed to understand the mechanisms that may explain standing balance
      deficits among people with AT.

PMID- 29054750
TI  - Onset of psychosis following strokes to the cerebellum and thalamus.

PMID- 29054751
TI  - NG2/CSPG4 and progranulin in the posttraumatic glial scar.
AB  - Traumatic injury of the central nervous system is one of the leading causes of
      death and disability in young adults. Failure of regeneration is caused by
      autonomous neuronal obstacles and by formation of the glial scar, which is
      essential to seal the injury but also constitutes a barrier for regrowing axons.
      The scar center is highly inflammatory and populated by NG2+ glia, whereas
      astrocytes form the sealing border and trap regrowing axons, suggesting that the
      non-permissive environment of activated astrocytes and extracellular matrix
      components is one of the reasons for the regenerative failure. Particularly,
      secreted chondroitin-sulfate proteoglycans, CSPGs, of the lectican family hinder
      axonal regrowth. In contrast, the transmembrane CSPG, NG2/CSPG4, appears to be
      functionally closer related to axon growth permissive heparan sulfate
      proteoglycans, HSPGs, and synaptic adhesion molecules, which all regulate
      synaptic signaling and plasticity upon alpha-secretase mediated shedding.
      Consequently, knockout of NG2/CSPG4 aggravates tissue loss, inflammation and
      neurologic deficits after brain injury, a phenotype partly mimicked by deletion
      of HSPG-binding proteins such as the HSPG2/perlecan-interacting protein,
      progranulin that is also a functional ligand of Notch and Eph2a. Indeed,
      structural features or progranulin's targets and NG2 may point to direct
      reciprocal regulations that may act in concert to overcome injury-evoked
      inflammation and neuronal dystrophy. This review provides an overview of the
      pathophysiology of the glial scar after brain injury, with a specific focus on
      NG2/CSPG4, its functions before and after shedding and putative reciprocal
      influences with the glycoprotein progranulin.

PMID- 29054752
TI  - Esophageal lesions following button-battery ingestion in children: Analysis of
      causes and proposals for preventive measures.
AB  - OBJECTIVES: To study recent cases of esophageal injury due to button-battery
      ingestion in children presenting in pediatric ENT emergency departments of the
      Paris area of France (Ile-de-France region), in order to propose appropriate
      preventive measures. MATERIAL AND METHOD: A retrospective descriptive single
      center study included all children under 15 years of age, presenting in pediatric
      ENT emergency departments between January 2008 and April 2014 for button-battery
      ingestion with esophageal impaction requiring emergency removal. RESULTS: Twenty
      two boys and 4 girls, with a median age of 25 months, were included. Twenty-five
      of the 26 batteries had diameters of 20mm or more. Median esophageal impaction
      time was 7 hours 30 minutes (range, 2 to 72 hours). The complications rate was
      23%. Mean hospital stay cost was ?38,751 (range, ?5130-119,737). The origin of
      the battery was known in 23 of the 26 cases: remote control without screw-secured
      compartment (42.3%), open battery pack (15.4%), children's toy (15.3%), camera
      (7.7%), watch (1 case) and hearing aid without screw-secured compartment (1
      case). CONCLUSION: Esophageal lesions due to ingestion of button-batteries in
      children are almost always due to batteries larger than 20mm in diameter, mostly
      from devices with a poorly protected compartment, or batteries that are not
      individually packaged. These lesions cause serious complications in a quarter of
      cases and their management entails high health costs. Legislation requiring screw
      secured compartments and individual blisters for batteries could have prevented
      69.2% of the ingestions.

PMID- 29054753
TI  - Risk of fracture in transfusion-naive thalassemia population: A nationwide
      population-based retrospective cohort study.
AB  - In thalassemia major or transfusion-dependent thalassemia patients, osteoporosis
      related bone complications such as fracture events are common. However, no
      studies have investigated the risk of fracture in transfusion-naive thalassemia
      population. Therefore, we conducted a longitudinal nationwide cohort study to
      determine whether this population has an increased risk of fracture. This
      nationwide, population-based cohort study analyzed data from 1998 to 2010
      obtained from the Taiwanese National Health Insurance Research Database, with a
      follow-up period extending until the end of 2011. We identified cases with
      transfusion-naive thalassemia and selected a comparison cohort that was frequency
      matched according to age and year of diagnosis of thalassemia at a ratio of one
      subject with thalassemia to four subjects in the control group. We analyzed the
      risk of fracture events to occur in transfusion-naive thalassemia cases by using
      Cox proportional hazards regression models. Totally, the study recruited 1369
      transfusion-naive thalassemia subjects and 5416 controls. We identified a total
      of 71 cases with fracture events within the thalassemia group and 204 within the
      control group. The overall risks for developing fracture events were 1.35-fold
      higher in transfusion-naive thalassemia individuals than the comparison cohort
      after adjusting for age, sex and comorbidities. Most fracture events were
      observed in male transfusion-naive thalassemia individuals rather than the normal
      population. In subgroup analysis, there was a 1.46-fold higher risk to develop
      upper-limb fracture in the thalassemia group than in the control groups. In
      conclusion, our long-term, cohort study results showed that there was a higher
      risk for the development of fractures in transfusion-naive thalassemia
      individuals, particularly in male cases.

PMID- 29054754
TI  - Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo
      (Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex.
AB  - The Escherichia coli holo-(acyl carrier protein) synthase (ACPS) catalyzes the
      coenzyme A-dependent activation of apo-ACPP to generate holo-(acyl carrier
      protein) (holo-ACPP) in an early step of fatty acid biosynthesis. E. coli ACPS is
      sufficiently different from the human fatty acid synthase to justify the
      development of novel ACPS-targeting antibiotics. Models of E. coli ACPS in
      unliganded and holo-ACPP-bound forms solved by X-ray crystallography to 2.05and
      4.10A, respectively, revealed that ACPS bound three product holo-ACPP molecules
      to form a 3:3 hexamer. Solution NMR spectroscopy experiments validated the ACPS
      binding interface on holo-ACPP using chemical shift perturbations and by
      determining the relative orientation of holo-ACPP to ACPS by fitting residual
      dipolar couplings. The binding interface is organized to arrange contacts between
      positively charged ACPS residues and the holo-ACPP phosphopantetheine moiety,
      indicating product contains more stabilizing interactions than expected in the
      enzyme:substrate complex. Indeed, holo-ACPP bound the enzyme with greater
      affinity than the substrate, apo-ACPP, and with negative cooperativity. The first
      equivalent of holo-ACPP bound with a KD=62+/-13nM, followed by the binding of two
      more equivalents of holo-ACPP with KD=1.2+/-0.2MUM. Cooperativity was not
      observed for apo-ACPP which bound with KD=2.4+/-0.1MUM. Strong product binding
      and high levels of holo-ACPP in the cell identify a potential regulatory role of
      ACPS in fatty acid biosynthesis.

PMID- 29054755
TI  - Association of polymorphic variants in IL1B gene with secretion of IL-1beta
      protein and inflammatory markers in north Indian rheumatoid arthritis patients.
AB  - The proinflammatory cytokine interleukin-1beta (IL-1beta) is a key mediator of
      inflammation which affects cell proliferation and differentiation. IL-1beta is
      considered to contribute to the pathophysiology of rheumatoid arthritis (RA).
      Polymorphisms in cytokine genes are highly influenced by ethnicity. Hence, in
      this study polymorphism of the IL1B-511(C/T) within promoter region was analyzed
      by using polymerase chain reaction-restriction fragment length Polymorphism (PCR
      RFLP) in 187 RA patients and 214 controls. The prevalence of different genotypes
      and allelic frequency distribution was compared in RA patients and controls.
      Levels of inflammatory markers and serum levels of IL-1beta were estimated by
      ELISA The serum inflammatory markers levels were significantly higher in RA
      patients as compared to controls (RF=127.3+/-21.3U/mL, Anti-CCP=17.8+/-8.3U/mL,
      CRP=17.86+/-7.1mg/L and IL-1beta=21.25+/-4.19pg/mL in RA patients p<0.01). The
      frequency of heterozygous mutant (C/T) and homozygous mutant (T/T) variants were
      significantly higher in RA patients as compared to controls and the odds ratios
      by logistic regression were (OR=2.2, p<0.001) and (OR=3.21, p<0.01) respectively.
      The association persisted on combining the heterozygous mutant and homozygous
      mutant (CT+TT) together as compared to controls (OR=2.39; p<0.001). Positive and
      significant (p<0.05) correlation of circulating IL-1beta levels with RF
      (r=0.232), anti-CCP (r=0.207) and CRP (r=0.166) among RA patients were found. The
      levels of anti-CCP were significantly higher in homozygous mutant variants (TT)
      as well as the heterozygous mutant variants (C/T) in comparison to the wild
      variants (CC) (p<0.01). The results of this study reveal that mutant allele (T)
      of IL1B-511 promoter SNP tends to be associated with elevated anti-CCP and IL
      1beta levels as observed in RA patients and hence disease susceptibility.

PMID- 29054757
TI  - MiR-767 promoted cell proliferation in human melanoma by suppressing CYLD
      expression.
AB  - MicroRNAs (miRNAs) have emerged as critical regulators for cancer development and
      progression of human melanoma. However, the potential molecular mechanism of miR
      767 in human melanoma has not been intensively investigated. In this present
      study, we confirmed that miR-767 was frequently up-regulated in human melanoma
      tissues and cell lines. Ectopic expression of miR-767 promoted cell proliferation
      in human melanoma cell lines A375 and WM35, whereas miR-767-in reversed the
      function. Bioinformatics analysis revealed that cylindromatosis (CYLD) was
      hypothesized to be a possible target gene of miR-767, and this was confirmed by
      luciferase activity assay. Knockdown of CYLD counteracted the proliferation
      arrest by miR-767-in in melanoma cells A375 and WM35. In conclusion, our study
      indicated that miR-767 acted as a role of tumor promoter by targeting CYLD in
      human melanoma, and might serve as a prognostic or therapeutic target for human
      melanoma.

PMID- 29054756
TI  - A lncRNA-H19 transcript from secondary hair follicle of Liaoning cashmere goat:
      Identification, regulatory network and expression regulated potentially by its
      promoter methylation.
AB  - The H19 transcript (imprinted maternally expressed transcript) is well-known as
      long noncoding RNA (lncRNA), and it is thought to be associated with the
      inductive capacity of dermal papilla cells for hair-follicle reconstruction. In
      this study, we isolated and characterized a lncRNA-H19 transcript from the
      secondary hair follicle of Liaoning cashmere goat. Also, we investigated its
      transcriptional pattern and methylation status of H19 gene in secondary hair
      follicle of this breed during different stages of hair follicle cycle. Nucleotide
      composition analysis indicated that guanine (G) and cytosine (C) are the dominant
      nucleotides in the lncRNA-H19 transcript of Liaoning cashmere goat with the
      highest frequency distribution (11.25%) of GG nucleotide pair. The regulatory
      network showed that lncRNA-H19 transcript appears to have remarkably diverse
      regulatory relationships with its related miRNAs and the potential target genes.
      In secondary hair follicle, the relative expression of lncRNA-H19 transcript at
      the anagen phase is significantly higher than that at both telogen and catagen
      phases suggesting that lncRNA-H19 transcript might play essential roles in the
      formation and growth of cashmere fiber of goat. Methylation analysis indicated
      that the methylation of the promoter region of H19 gene most likely participates
      in its transcriptional suppression in secondary hair follicle of Liaoning
      cashmere goat.

PMID- 29054758
TI  - Cystic fibrosis transmembrane regulator haplotypes in households of patients with
      cystic fibrosis.
AB  - INTRODUCTION: Nearly 2000 mutations in the cystic fibrosis transmembrane
      regulator (CFTR) gene have been reported. The F508del mutation occurs in
      approximately 50-65% of patients with cystic fibrosis (CF). However, molecular
      diagnosis is not always possible. Therefore, silent polymorphisms can be used to
      label the mutant allele in households of patients with CF. OBJECTIVE: To verify
      the haplotypes of four polymorphisms at the CFTR locus in households of patients
      with CF for pre-fertilization, pre-implantation, and prenatal indirect mutation
      diagnosis to provide better genetic counseling for families and patients with CF
      and to associate the genotypes/haplotypes with the F508del mutation screening.
      METHODS: GATT polymorphism analysis was performed using direct polymerase chain
      reaction amplification, and the MP6-D9, TUB09 and TUB18 polymorphism analyses
      were performed using restriction fragment length polymorphism. RESULTS: Nine
      haplotypes were found in 37 CFTR alleles, and of those, 24 were linked with the
      F508del mutation and 13 with other CFTR mutations. The 6 (GATT), C (MP6-D9), G
      (TUB09), and C (TUB18) haplotypes showed the highest prevalence (48%) of the
      mutant CFTR allele and were linked to the F508del mutation (64%). In 43% of
      households analyzed, at least one informative polymorphism can be used for the
      indirect diagnostic test. CONCLUSION: CFTR polymorphisms are genetic markers that
      are useful for identifying the mutant CFTR alleles in households of patients with
      CF when it is not possible to establish the complete CFTR genotype. Moreover, the
      polymorphisms can be used for indirect CFTR mutation identification in cases of
      pre-fertilization, pre-implantation and prenatal analysis.

PMID- 29054759
TI  - CRELD1 gene variants and atrioventricular septal defects in Down syndrome.
AB  - Congenital heart defects (CHD) are seen in around 40% of the Down syndrome
      patients. Atrioventricular Septal Defect (AVSD) or endocardial cushion defect is
      commonest form of CHD in these children. CRELD1 gene is implicated in causation
      of sporadic AVSD. In the present study, we evaluated the association and
      significance of CRELD1 variants with AVSD in Down syndrome (DS) patients.
      Sequencing was done in blood samples from 3 groups: group I (DS with AVSD), group
      II (DS without AVSD) and group III (non-syndromic AVSD cases). Twenty two
      variants in CRELD1 gene were identified, comprising of sixteen novel and six
      previously reported variants. However, on the basis of sequence, as well as
      structure analysis, the variant c.973G>A(p.Glu325Lys) variant was identified only
      in DS having AVSD group which was predicted to have significant effects on
      calcium binding of putative CRELD1 protein. Since CRELD1 gene acts as a regulator
      of calcineurin/NFATc1 signaling which is crucial for the regulation of cardiac
      development by dephosphorylation of the transcription factor, NFAT(nuclear factor
      of activated T cells),in cytoplasm, the variation in cb-EGF-like calcium binding
      domain in CRELD1 protein is likely to have pathogenic consequences. Thus, we
      conclude that the CRELD1 gene is likely to have a major role in causation of AVSD
      phenotype in selected DS patients.

PMID- 29054760
TI  - Polymorphisms of vitamin K-related genes (EPHX1 and VKORC1L1) and stable warfarin
      doses.
AB  - The aim of this study was to investigate the possible effects of EPHX1 and
      VKORC1L1 polymorphisms on variability of responses to warfarin. Sixteen single
      nucleotide polymorphisms (SNPs) in 201 patients with stable warfarin doses were
      analyzed including genes of VKORC1, CYP2C9, CYP4F2, GGCX, EPHX1 and VKORC1L1.
      Univariate analysis was conducted for the association of genotypes with stable
      warfarin doses. Multiple linear regression analysis was used to investigate
      factors that independently affected the inter-individual variability of warfarin
      dose requirements. The rs4072879 of VKORC1L1 (A>G) was significantly associated
      with stable warfarin doses; wild homozygote carriers (AA) required significantly
      lower stable warfarin doses than those with the variant G allele (5.02+/-1.56 vs.
      5.96+/-2.01mg; p=0.001). Multivariate analysis showed that EPHX1 rs1877724 and
      VKORC1L1 rs4072879 accounted for 1.5% and 1.3% of the warfarin dose variability.
      Adding EPHX1 and VKORC1L1 SNPs to the base model including non-genetic variables
      (operation age, body weight and the therapy of ACEI or ARB) and genetic variables
      (VKORC1 rs9934438, CYP2C9 rs1057910, and CYP4F2 rs2108622) gave a number needed
      to genotype of 34. This study showed that polymorphisms of EPHX1 and VKORC1L1
      could be determinants of stable warfarin doses.

PMID- 29054761
TI  - Differential expression levels of plasma microRNA in Hashimoto's disease.
AB  - BACKGROUND: The altered expression of circulating miRNAs has been discovered in
      many autoimmune diseases (ADs). With rare existing research, it is still unclear
      in Hashimoto's thyroiditis (HT). We detected plasma miRNA expression of HT
      patients in this three-stage designed study. METHODS: Differently expressed
      miRNAs (4 HT pools vs. 1 normal control pool) were identified using quantitative
      reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel
      (miRCURY-Ready-to-Use- PCR-Human- panel-I+II-V1.M) in the initial discovery
      stage. These miRNAs were then confirmed in the training stage and further
      validated in the testing stage using qRT-PCR with 64 (32 HT vs. 32 NCs) and 136
      samples (68 HT vs. 68 NCs), respectively. RESULTS: A total of 10 miRNAs showed
      differential expression through the training stage. For further validation in the
      testing stage, expression of 6 miRNAs (miR-205, miR-20a-3p, miR-375, miR-296, miR
      451, miR-500a) were consistent with those in the training stage. Combination
      results showed that these 6 miRNAs were significantly up-regulated in peripheral
      plasma of HT patients compared with normal controls (P<0.05). In addition, the
      six-miRNA signature was evaluated to be a potential diagnostic marker of HT. The
      areas under the receiver operating characteristic curve of the signature were
      0.80, 0.75 and 0.69 for the training, testing and the combined stages,
      respectively. Three miRNAs were associated with TSH levels in HT patients (miR
      451, P=0.043; miR-375, P=0.043; miR-500a, P=0.043). Additionally, miR-20a-3p was
      related with TgAb level (P=0.046). CONCLUSIONS: We identified a miRNA signature
      including six dysregulated plasma miRNAs which could act as a diagnostic marker
      in plasma of HT, providing more evidence and better understanding for the
      association between circulating miRNAs and autoimmune diseases.

PMID- 29054762
TI  - MiR-34a, as a suppressor, enhance the susceptibility of gastric cancer cell to
      luteolin by directly targeting HK1.
AB  - Luteolin is a flavonoid compound derived from Lonicera japonica Thunb, which has
      been reported to exert anticancer effects on different types of tumors. miRNAs
      are a kind of endogenous non-coding small RNAs, which involved in occurrence and
      development of multi cancer, including miR-34a. However, the relationship between
      miR-34a and luteolin's susceptibility to cancer cells still remains unclear. In
      this study, we explored the roles of miR-34a and the effects of luteolin on GC
      cells as well as the underlying mechanism of miR-34a in mediating the
      susceptibility of GC cell to luteolin. Retrospectively study revealed that miR
      34a expression was downregulated in human primary GC tissues compared with non
      tumor tissues and low miR-34a expression was associated with a significantly
      shorter overall survival and disease-free survival. MiR-34a overexpression could
      inhibit GC cells and induce G1 phase arrest via p53/p21 and MAPK /ERK pathways.
      Luteolin decreased viability of GC cells in a dose-dependent manner. Meanwhile,
      miR-34a was found to be markedly upregulated in GC cells induced by luteolin and
      decreased miR-34a level was found in the artificial luteolin-resistant GC cells.
      Upregulation of miR-34a in luteolin-resistant GC cell could enhance the
      sensibility of GC cells to luteolin. On the other hand, miR-34a inhibitor could
      partly counter the anticancer effect of luteolin. In a further assay, we also
      found that targeting miR-34a could mediate the susceptibility of mouse xenografts
      to luteolin. Subsequent study found that HK1 was a direct target of miR-34a and
      downregulated HK1 mRNA or protein levels were presented after miRNA-34a
      overexpression in GC cells. Moreover, HK1 protein levels was decreased after
      luteolin treatment and partly restored when co-treated with luteolin and miR-34a
      inhibitor. Downregulation of HK1 in luteolin-resistant GC cell could increase the
      cell's sensitivity to luteolin. Therefore, our findings firstly suggested that
      miR-34a could modulate the susceptibility of gastric cancer cell to luteolin via
      targeting HK1, potentially benefiting GC patients' treatment in the future.

PMID- 29054763
TI  - Association of genetic variants of hemostatic genes with myocardial infarction in
      Egyptian patients.
AB  - Hemostatic genes polymorphisms are well known to be associated with venous
      thrombosis, but their association with arterial thrombosis especially myocardial
      infarction (MI) remains to be clarified. We investigated the role of three
      hemostatic gene polymorphisms, prothrombin G20210A, factor XIII (FXIII) Val34Leu
      (G/T), and fibrinogen-beta-455G/A and their coexistence in Egyptian patients with
      MI. The possible correlation of these polymorphisms with plasma fibrinogen level
      was also evaluated. The study included 120 patients with MI and 60 healthy
      volunteers. Gene polymorphisms were tested using multiplex polymerase chain
      reaction and reverse-hybridization technique. Plasma fibrinogen level was
      determined by ELISA. Our study showed an increased risk of MI with fibrinogen
      beta-455G/A heterozygosity as well as FXIII Val34Leu homo and heterozygosity. In
      addition, the FXIII T allele (Leu34) and fibrinogen beta-455A allele were
      significantly associated with MI. Conversely, the prevalence of prothrombin
      mutation did not differ between patients with MI and controls. Combined carriers
      of FXIII Leu34 and fibrinogen-beta455A alleles were at higher risk of MI, whereas
      combined FXIII Val34Leu and prothrombin 20210A polymorphisms did not show
      increased risk for MI compared with controls. Plasma fibrinogen levels were
      significantly higher in patients with MI than controls. In MI patients, plasma
      fibrinogen levels were significantly higher in those with FXIII GT/TT or
      fibrinogen beta-455 GA, while were significantly lower in those with prothrombin
      20210 GA compared with patients with wild type genotypes. In conclusion, our
      results suggest a possible thrombotic predisposition of FXIII Val34Leu,
      fibrinogen beta-455G/A polymorphisms and their coexistence for MI. These
      polymorphisms may add complexity to disease pathology by increasing plasma
      fibrinogen level. Extended studies are needed to confirm our results;
      nevertheless, these data may be implicated in genetic counseling and screening of
      high-risk individuals.

PMID- 29054764
TI  - TRPM8 activation improves energy expenditure in skeletal muscle and exercise
      endurance in mice.
AB  - Skeletal muscle serving as the major organ is responsible for energy expenditure
      and exercise endurance, which directly influence cardiometabolic risk factors.
      Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective
      cation channel, plays vital roles in the regulation of various cellular
      functions. It has been reported that TRPM8 activation enhanced the energy
      metabolism of adipocytes. However, the involvement of TRPM8 in the energy
      metabolism of skeletal muscle remains unexplored. Our data revealed that TRPM8
      was expressed in cultured C2C12 myocytes. Menthol treatment increased uncoupling
      protein 1 (UCP1) and peroxisome proliferator-activated receptor-gamma coactivator
      1alpha (PGC1alpha) expression in C2C12 myotubes through TRPM8 activation.
      Moreover, dietary menthol upregulated the expression of UCP1 and PGC1alpha in
      skeletal muscle of mice. In addition, dietary menthol enhanced exercise endurance
      and reduced blood lactic acid and triglycerides through TRPM8 activation. It is
      concluded that dietary menthol improves energy metabolism and exercise endurance
      by increasing UCP1 and PGC1alpha in skeletal muscles, suggesting dietary menthol
      might be a novel therapeutic approach for cardiometabolic diseases management and
      prevention.

PMID- 29054765
TI  - Characterization of germline mutations in familial lung cancer from the Chinese
      population.
AB  - Compared with numerous studies of somatic mutations using sporadic lung cancer,
      the research into germline mutations using familial lung cancer (FLC) is limited.
      In the present study, we used FLC samples obtained from the Chinese population in
      highly air-polluted regions to screen for novel germline mutations in lung
      cancer. Through a whole genome sequencing (WGS) analysis of the nine subjects
      (four lung cancer patients and five normal family members of FLC), we obtained a
      whole genome dataset of DNA alterations in FLC samples. A total of 1218 genes
      were identified with mutations of multiple types. Subsequently, the top 12 highly
      mutated genes were selected for validation by polymerase chain reaction and DNA
      sequencing in an expanded sample set including FLC, sporadic lung cancer, and
      healthy population. Mutations of the five genes (ARHGEF5, ANKRD20A2, ZNF595,
      ZNF812, MYO18B) may be potential germline mutations of lung cancer. We also
      analyzed specific mutations within the 12 genes and found that some specific
      mutations within the MUC12, FOXD4L3 and FOXD4L5 genes showed higher frequencies
      in the samples of FLC and/or lung cancer tissue, compared with the healthy
      population. Moreover, some genes with copy number variation may be potentially
      associated with a predisposition to lung cancer. Furthermore, non-coding DNA
      alterations of the WGS data in FLC were systematically analyzed and arranged.
      Interestingly, we found that germline mutations also occurred in many genes of
      non-coding RNA. This study uncovered the mutation spectrum in FLC and provided
      important clues for the evaluation of the genetic susceptibility to lung cancer.

PMID- 29054766
TI  - Rethinking genotype-phenotype correlations in papillorenal syndrome: a case
      report on an unusual congenital camptodactyly and skeletal deformity with a
      heterogeneous PAX2 mutation of hexanucleotide duplication.
AB  - Papillorenal syndrome (PRS), an autosomal dominant inherited condition, is
      clinically featured by renal hypoplasia and optic nerve dysplasia. Based on
      current knowledge of genotype-phenotype correlations in PRS, mutations in the
      Paired box 2 (PAX2) gene have been recognized as a critical pathogenesis of
      typical renal and optic disease manifestations. However, little information is
      currently available on the skeletal abnormalities of PRS and the potential
      contribution of PAX2 mutations. Here, we present a case of a 10-year-old female
      PRS patient with the typical features of chronic renal failure and severe myopia,
      but was unexpectedly discovered camptodactyly of her left middle finger which
      affects the proximal interphalangeal joint. Pathologically, the camptodactyly was
      further indicated by radiology as a skeletal deformity, demonstrating a decline
      of bone mineral density and disappearance of joint space. Molecular diagnostics
      revealed a heterozygous mutation, 220_225dup, in the exon 3 of her PAX2 gene,
      which is de novo considering the lack of this mutation in her non-consanguineous
      parents. This mutation leads to duplication of glutamic acid at position 74 and
      tyrosine at position 75 in PAX2 protein, which may influence the DNA-binding
      function. Besides, the absence of Spalt like transcription factor 4 (SALL4)
      mutation excluded the diagnosis of acro-renal-ocular syndrome (AROS), of which
      clinical characteristics are similar to our patient's. This case unravels a
      previously unrecognized phenotype of camptodactyly due to a significant skeletal
      deformity of PRS with a heterogeneous PAX2 mutation of hexanucleotide
      duplication. This report challenges against the current belief of genotype
      phenotype correlations in PRS.

PMID- 29054767
TI  - Identifying eustachian tube dysfunction prior to hyperbaric oxygen therapy: Who
      is at risk for intolerance?
AB  - PURPOSE: Determine whether specific risk factors, symptoms and clinical
      examination findings are associated with hyperbaric oxygen therapy (HBOT)
      intolerance and subsequent tympanotomy tube placement. MATERIALS AND METHODS: A
      retrospective case series with chart review was conducted from 2007 to 2016 of
      patients undergoing HBOT clearance at a tertiary care university hospital in an
      urban city. Eighty-one (n=81) patient charts were reviewed for risk factors,
      symptoms and clinical examination findings related to HBOT eustachian tube
      dysfunction and middle ear barotrauma. Relative risk was calculated for each
      variable to determine risk for HBOT intolerance and need for tympanotomy tube
      placement. Risk factor, symptom, physical examination and HBOT complication
      susceptibility scores were calculated for each patient. RESULTS: Mean risk
      factor, clinical and HBOT complication-susceptibility scores were significantly
      higher in patients who did not tolerate HBOT compared to patients who tolerated
      HBOT. Patients reporting a history of otitis media, tinnitus, and prior ear
      surgery were at a higher risk for HBOT intolerance. Patients reporting a history
      of pressure intolerance and prior ear surgery were more likely to undergo
      tympanotomy tube placement. Patients noted to have otologic findings prior to
      HBOT were at a higher risk for both HBOT intolerance and tympanotomy tube
      placement. CONCLUSIONS: A thorough otolaryngological evaluation can potentially
      predict and identify patients at risk for HBOT intolerance and tympanotomy tube
      placement.

PMID- 29054768
TI  - A branching process model of heterogeneous DNA damages caused by radiotherapy in
      in vitro cell cultures.
AB  - This paper deals with the dynamic modeling and simulation of cell damage
      heterogeneity and associated mutant cell phenotypes in the therapeutic responses
      of cancer cell populations submitted to a radiotherapy session during in vitro
      assays. Each cell is described by a finite number of phenotypic states with
      possible transitions between them. The population dynamics is then given by an
      age-dependent multi-type branching process. From this representation, we obtain
      formulas for the average size of the global survival population as well as the
      one of subpopulations associated with 10 mutation phenotypes. The proposed model
      has been implemented into Matlab(c) and the numerical results corroborate the
      ability of the model to reproduce four major types of cell responses: delayed
      growth, anti-proliferative, cytostatic and cytotoxic.

PMID- 29054770
TI  - Challenges in rendering Coral Triangle habitat richness in remotely sensed
      habitat maps: The case of Bunaken Island (Indonesia).
AB  - The Coral Triangle is the epicenter of marine biodiversity, yet the numbers of
      habitats that can be found on coral reefs remain poorly described. First surveys
      for habitat mapping in Indonesia revealed a high number of habitats (>150) even
      for structurally simple reefs. To be able to represent all these habitats,
      typical habitat mapping procedures and performances are poorly effective even
      using very high resolution satellite images. Using Bunaken Island (North
      Sulawesi, Indonesia) as a case study, we devised a way to maintain all the in
      situ habitat information in remote sensing habitat map products without loss and
      with mapping procedures based on photo-interpretation. The result is a product
      which is consistent with a per-polygon fuzzy classification. As such, it is a
      complex product that meets our habitat representation goal, but its complexity
      can also limit its immediate use by managers and conservation planners when
      analyses per habitat are needed.

PMID- 29054769
TI  - Positive end-expiratory pressure adjusted for intra-abdominal pressure - A pilot
      study.
AB  - PURPOSE: Intra-abdominal hypertension (IAH) is associated with impaired
      respiratory function. Animal data suggest that positive end-expiratory pressure
      (PEEP) levels adjusted to intra-abdominal pressure (IAP) levels may counteract
      IAH-induced respiratory dysfunction. In this pilot study, our aim was to assess
      whether PEEP adjusted for IAP can be applied safely in patients with IAH.
      MATERIALS AND METHODS: We included patients on mechanical ventilation and with
      IAH. Patients were excluded with severe cardiovascular dysfunction or severe
      hypoxemia or if the patient was in imminent danger of dying. Following a
      recruitment manoeuvre, the following PEEP levels were randomly applied: PEEP of
      5cmH2O (baseline), PEEP=50% of IAP, and PEEP=100% of IAP. After a 30min
      equilibration period we measured arterial blood gases and cardio-respiratory
      parameters. RESULTS: Fifteen patients were enrolled. Six (41%) patients did not
      tolerate PEEP=100% IAP due to hypoxemia, hypotension or endotracheal cuff leak.
      PaO2/FiO2 ratios were 234 (68), 271 (99), and 329 (107) respectively. The
      differences were significant (p=0.009) only between baseline and PEEP=100% IAP.
      CONCLUSIONS: PEEP=100% of IAP was not well-tolerated and only marginally improved
      oxygenation in ventilated patients with IAH.

PMID- 29054771
TI  - Spinal Cavernous Angioma Associated with Klippel-Trenaunay-Weber Syndrome: Case
      Report and Literature Review.
AB  - BACKGROUND: Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital vascular
      disorder characterized by the classic triad of cutaneous nevi, venous
      varicosities, and osseous and soft tissue hypertrophy of the affected limb.
      Various vascular anomalies of the central nervous system have also been described
      in patients with KTWS. The English language literature to date contains 6 reports
      of associations between KTWS and spinal cord cavernous angioma (CA), but
      management of these patients has not been well described. CASE DESCRIPTION: A 23
      year-old woman was admitted to our institution with acute onset of leg weakness
      accompanied by upper back pain. Thoracic magnetic resonance imaging of the spinal
      cord showed a heterogeneous mass with a slit component at the T1-2 level. The
      patient underwent left hemilaminectomy followed by removal of the tumor, and her
      neurologic symptoms improved postoperatively. Pathologic examination showed the
      spinal lesion was characterized by hemosiderin deposition and thin-walled
      vascular channels surrounded by fibrous tissue. CONCLUSIONS: This is the first
      report to provide a detailed pathologic description of the features of spinal CA
      in a patient with KTWS. Assessment of the clinical features and management of CA
      associated with KTWS are discussed. This syndrome is rare, and further experience
      in the treatment of these patients is needed. However, considering that the
      pathologic findings of spinal CA in patients with KTWS include the typical
      features of CA, the management of CA in patients with KTWS may be identical to
      management of isolated CA.

PMID- 29054772
TI  - Through Clinical Observation: The History of Priapism After Spinal Cord Injuries.
AB  - Since ancient times, physicians of antiquity noted the occurrence of priapism in
      some spinal cord injuries. Although priests saw it as a consequence of curses and
      witchcraft, after clinical observations of the Middle Ages and Renaissance, the
      first medical hypotheses emerged in the 17th-19th centuries completed and argued
      by neuroscience and neurology developed in the European laboratories and
      hospitals. This study aims to present a short overview of the history of clinical
      observations of posttraumatic male priapism after spinal cord injuries since
      antiquity until the beginning of the 20th century.

PMID- 29054773
TI  - Microsurgical versus Endovascular Treatments for Blood-Blister Aneurysms of the
      Internal Carotid Artery: A Retrospective Study of 83 Patients in a Single Center.
AB  - BACKGROUND: Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA)
      are challenging lesions with high morbidity and mortality. Both surgical and
      endovascular approaches have been used to treat BBAs; however, little is known
      about their safety and efficacy. OBJECTIVE: To review our experience with the
      treatment of BBAs and explore the optimal treatment strategy. METHODS: A total of
      83 patients with BBAs were reviewed retrospectively. The characteristics of the
      patients and the aneurysms, treatment results, and follow-up outcomes were
      analyzed. RESULTS: The cohort comprised 52 females and 31 males with a mean age
      of 46.6 years; 33 patients were assigned to the microsurgical therapy.
      Subsequently, 27/33 patients underwent surgical clipping, 4/33 underwent trapping
      without bypass, 2/33 underwent wrapping, and 50 patients underwent endovascular
      therapy, including stent-assisted coiling (49 patients) and coiling (1 patient).
      Intraoperative rupture occurred in 14 and 4 patients in the microsurgical and
      endovascular groups, respectively. Ischemic events occurred in 16 and 8 patients
      in the microsurgical and endovascular groups, respectively. At 1-year follow-up,
      a favorable clinical outcome was achieved in 18 (54.5%) and 38 (76.0%) patients
      in the microsurgical and endovascular groups, respectively. The multivariate
      regression model showed that the treatment strategies, Fisher grade, and
      vasospasm contributed significantly to the prediction of outcome for 1 year.
      CONCLUSIONS: BBAs are challenging vascular lesions with poor prognosis.
      Endovascular treatment may be more effective and safer with better outcomes than
      surgical approaches.

PMID- 29054774
TI  - Prognostic Significance of Ultraearly Hematoma Growth in Spontaneous
      Intracerebral Hemorrhage Patients Receiving Hematoma Evacuation.
AB  - OBJECTIVE: To investigate the association between ultraearly hematoma growth
      (uHG) and clinical outcome in patients with spontaneous intracerebral hemorrhage
      (sICH) receiving hematoma evacuation. METHODS: Supratentorial sICH patients
      receiving hematoma evacuation within 24 hours after ictus were enrolled in this
      study. uHG was defined as baseline hematoma volume/onset-to-computed tomography
      (CT) time (mL/h). The outcome was assessed by the modified Rankin Scale (mRS)
      score at 3 months. Unfavorable outcome was defined as mRS >2. RESULTS: A total of
      93 patients were enrolled in this study. The mean uHG was 10.3 +/- 5.5 mL/h. In
      69 (74.2%) of patients, the outcome was unfavorable at 3 months. The uHG in
      patients with unfavorable outcome were significantly higher than in those with
      favorable outcome (11.0 +/- 6.1 mL/h vs. 8.3 +/- 2.5 mL/h, P = 0.003). The
      optimal cutoff of uHG for predicting unfavorable outcome was 8.7 mL/h. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value of uHG >8.7 mL/h for predicting unfavorable outcome were 56.5%, 75.0%,
      86.7%, and 37.5%, respectively. CONCLUSIONS: uHG is a helpful predictor of
      unfavorable outcome in sICH patients treated with hematoma evacuation. The
      optimal cutoff of uHG to assist in predicting unfavorable outcome in sICH
      patients receiving hematoma evacuation is 8.7mL/h.

PMID- 29054775
TI  - Paul of Aegina (625-690): His Work and His Contribution to Neurologic Surgery:
      Trephinations and Laminectomies in the Dark Ages.
AB  - The purpose of this historical review is to summarize the work of Paul of Aegina,
      especially his contribution to the treatment of neurosurgical disorders and
      trauma. Paul performed trephinations for head injuries in the tradition of the
      Egyptian and the Greek schools of medicine. However, he was an innovator in the
      treatment of several spine injuries, as his choice to perform laminectomies and
      his description of them as safe and successful is unprecedented in the history of
      the recorded medicine and surgery. Our search of the literature shows that Paul
      was the first to include in his practice such a surgical technique, and, in this
      way, he is an innovator, since Hippocrates described the results of spine surgery
      as disastrous for the patient. Thus, he may be considered the historic father of
      spine surgery for his pioneering surgical innovations. This shows clearly that
      innovation in science and medicine was significantly increased through the rise
      of Islam and the Arabic conquest of the Middle East. The so-called "Dark Ages"
      were not so dark after all.

PMID- 29054776
TI  - Intracranial Pressure-Guided Shunt Valve Adjustments with the Miethke Sensor
      Reservoir.
AB  - BACKGROUND: Telemetric intracranial pressure (ICP) monitoring seems to be a
      promising therapy-supporting option in shunt-treated patients. Benefits become
      obvious when headaches are unspecific and clinical symptoms cannot be related to
      possible overdrainage or underdrainage. In this study, we evaluated a new
      telemetric device to individually adjust shunt valves according to ICP
      measurements. METHODS: Between December 2015 and November 2016, 25 patients with
      suspected suboptimal shunt valve settings underwent insertion of a telemetric ICP
      sensor (Sensor Reservoir; Christoph Miethke, Potsdam, Germany). Over a 1-year
      period, a total of 183 telemetric ICP measurements and 85 shunt valve adjustments
      were carried out. Retrospective statistic analyses focused on valve adjustments,
      ICP values, and clinical outcomes. RESULTS: ICP-guided valve adjustments
      positively changed the clinical state in 18 out of 25 patients. Clinical
      improvement over time was associated with significant changes of the valve
      settings and ICP values. Interestingly, a therapeutically normalized ICP profile
      was not automatically associated with clinical improvement. CONCLUSIONS: The
      Sensor Reservoir is an important and valuable tool for shunt-treated patients
      suffering from drainage-related problems. The possibility to simultaneously
      recognize and solve shunt problems represents the decisive advantage.
      Nevertheless, measurements with the Sensor Reservoir did not allow for the
      determination of default valve settings or universal target ICP values.

PMID- 29054777
TI  - Hidden Blood Loss in Anterior Cervical Fusion Surgery: An Analysis of Risk
      Factors.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: Anterior cervical fusion surgery
      is widely used procedure in cervical spondylosis. When considering the blood
      reinfusion strategies of cervical fusion surgery, the amount of blood loss is one
      of the key elements. We usually calculate the blood loss according to the
      surgical bleeding plus the postoperative drainage; however, this method ignores
      the possibility that there may be hidden blood loss (HBL). METHODS: We performed
      a retrospective study to determine the risk factors for HBL in patients who
      underwent anterior cervical fusion surgery for degenerative spine from 2013 to
      2016. The Pearson correlation, Spearman correlation, and multivariate liner
      analysis were used to find association between patient characteristics and HBL.
      RESULTS: A total of 107 consecutive patients who underwent anterior cervical
      fusion surgery for degenerative spine in our hospital were reviewed. The amount
      of HBL was 261 mL, or 50% of the total blood loss. According to the model of
      multiple linear regression analysis, patient sex (P = 0.028) and American Society
      of Anesthesiologists physical status classification (P = 0.029) were independent
      risk factors contributing to HBL, but preoperative hematocrit was not (P =
      0.741). CONCLUSIONS: We concluded that sex and American Society of
      Anesthesiologists physical status classification were independent risk factors of
      HBL in anterior cervical fusion surgery. In addition, there was a high proportion
      of HBL in anterior cervical fusion. When considering the strategies of
      transfusion, we should pay attention to the risk factors for HBL.

PMID- 29054778
TI  - Validation of Prognostic Models to Predict Early Mortality in Spontaneous
      Intracerebral Hemorrhage: A Cross-Sectional Evaluation of a Singapore Stroke
      Database.
AB  - OBJECTIVE: Numerous scores have been developed for prognostication of outcomes in
      intracerebral hemorrhage (ICH). Prediction models must be validated internally
      and externally before they are considered widely applicable. We aim to
      independently externally validate and compare 3 prediction models (ICH score, ICH
      grading scale [ICH-GS], and simplified ICH [sICH]) in our population, which has
      not been previously done. METHODS: We reviewed 1338 patients with spontaneous ICH
      consecutively admitted to the National Neuroscience Institute, Singapore, between
      January 2009 and November 2013. We analyzed prospectively collected data of
      admission characteristics (clinical, neuroimaging, and laboratory findings). All
      3 scores prognosticated 30-day mortality. Validation was based on calibration,
      goodness-of-fit tests, and discrimination (area under receiver operating
      characteristic curve [AUC]). Akaike information criterion (AIC) and decision
      curve analysis (DCA) were used to directly compare the scores. RESULTS: All 3
      models showed good calibration and both the Hosmer-Lemeshow and the le Cessie-van
      Houwelingen-Copas goodness-of-fit test showed P values >0.05. AUCs ranged from
      0.86 to 0.90, indicating good discriminative ability, with the ICH-GS performing
      the best with the highest AUC, lowest AIC (849), and overall highest net benefit
      in the DCA. CONCLUSIONS: This study successfully independently validates the ICH
      score, ICH-GS, and sICH score in a large patient cohort with spontaneous ICH,
      which has not been previously done in this non-Western population. We recommend
      the use of the ICH-GS as a prognostication tool in our patients instead of the
      widely used ICH score.

PMID- 29054779
TI  - Prevalence, Characteristics, and Long-Term Prognosis of Epilepsy Associated with
      Pediatric Brain Tumors.
AB  - OBJECTIVE: We investigated the prevalence, onset, characteristics, and long-term
      course of epilepsy disease in children who underwent surgical intervention for
      diagnosed brain tumors. METHODS: We reviewed the medical records of children with
      diagnosed brain tumors who underwent surgery during 2004-2014 at the Hadassah
      Medical Center. All patients with epilepsy were invited to a clinical visit that
      included a neurologic examination. The primary outcome measures were neurologic
      status according to the Glasgow outcome score (GOS) and postoperative seizure
      outcome according to the Engel system. We compared clinical characteristics
      according to the timing of epilepsy onset. RESULTS: The mean follow-up was 49
      months. Of 128 patients included in the study, 44 (34%) had seizures; 23 (18%)
      developed epilepsy after surgery. Of the 30 patients with epilepsy who survived,
      21 (70%) are in Engel class I and 13% Engel are in class II. Forty-five percent
      of the children are classified as GOS 5. Children who developed epilepsy after
      surgery were more likely to be in GOS 1-2 than were those who had seizures before
      surgery (P = 0.0173). Children with seizures were more likely to have cortical
      tumors and less likely to have tumors of the posterior fossa (P < 0.001).
      Children who underwent gross total resection were less likely to have epilepsy (P
      < 0.001). CONCLUSIONS: We show a high incidence of epilepsy in the late course of
      pediatric brain tumor disease. In the long term, seizure outcome was excellent.
      However, postsurgical onset of epilepsy was associated with a less favorable
      neurologic outcome.

PMID- 29054780
TI  - Safe Burr Hole Surgery for Chronic Subdural Hematoma Using Dabigatran with
      Idarucizumab.
AB  - BACKGROUND: Chronic subdural hematoma (CSDH) is a common intracranial hematoma.
      The number of patients who undergo anticoagulant therapy including a direct oral
      anticoagulant (DOAC) is expected to increase. Recently, idarucizumab, the
      antidote for dabigatran, which is a DOAC, has been developed. We successfully
      treated CSDH with dabigatran using emergency burr hole surgery and idarucizumab.
      CASE DESCRIPTION: A 79-year-old Japanese man severely hit his head and visited
      the emergency department. Computed tomography (CT) showed tiny traumatic acute
      subdural hematoma, for which he was admitted. At that time, atrial fibrillation
      was newly detected, for which dabigatran, having a specific antidote
      (idarucizumab), was chosen and started 2 weeks after the discharge. Two months
      after the trauma episode, he revisited the emergency department because of acute
      left upper and lower limb motor weakness. CT revealed a midline shifted CSDH.
      Considering rush course of motor weakness and shifted brain, we performed
      emergency surgery using an antidote for dabigatran, idarucizumab. He was
      discharged 5 days after surgery without any complications or excessive
      perioperative hemorrhage. CONCLUSION: Dabigatran should be used for atrial
      fibrillation detected after head trauma. Emergency surgery can be safely
      performed for CSDH with dabigatran using idarucizumab.

PMID- 29054781
TI  - Superselective Thalamotomy in the Most Lateral Part of the Ventralis Intermedius
      Nucleus for Controlling Essential and Parkinsonian Tremor.
AB  - OBJECTIVE: The minimum and essential thalamic areas for reducing tremor were
      investigated in cases treated by superselective thalamotomy in the most lateral
      part of the ventralis intermedius nucleus (mlp-VIM). METHODS: Stereotactic
      superselective VIM thalamotomy with depth microrecording was performed in 21
      patients with essential tremor (ET) and 15 patients with tremor-dominant
      Parkinson disease (PD). A very small and narrow (axial plane) therapeutic lesion
      was formed as a square on the sagittal plane and inverse V on the axial plane in
      the mlp-VIM, which covered the kinesthetic response area topographically related
      to tremor. Patients with ET were followed up for 4.7 +/- 3.0 years and patients
      with PD for 7.9 +/- 3.9 years. RESULTS: Almost complete tremor control was
      achieved in all patients immediately after surgery and continued for up to 8
      years. A few adverse events were recognized but disappeared within 1 month
      without 1 patient with thalamic hemorrhage. The medial border of the therapeutic
      lesion was significantly more lateral in both patients with ET and patients with
      PD than the calculated standard target point and was in patients with PD than in
      patients with ET. The mean width was only about 2.4 mm. The individual
      differences of the adequate location of the therapeutic lesion were significantly
      greater in the ET than in the PD group. CONCLUSIONS: The important area for
      reducing tremor was small and narrow and was located in the mlp-VIM, where the
      proprioceptive ascending signals from the tremor-dominant body part are
      conducted. Superselective thalamotomy in the mlp-VIM was safe and effective for
      the long-term in patients with ET and PD.

PMID- 29054782
TI  - Multilevel Spondylolysis Repair Using the "Smiley Face" Technique with 3
      Dimensional Intraoperative Spinal Navigation.
AB  - BACKGROUND/OBJECTIVE: Multilevel spondylolysis is a rare cause of progressive
      lower back pain, and patients who fail conservative management are treated
      surgically. Direct repair methods can maintain mobility and lead to decreased
      morbidity compared with spinal fusion in single-level spondylolysis. In this
      paper, we present a patient with nonadjacent multilevel spondylolysis who
      underwent the "smiley face" technique of direct multilevel repair without fusion
      using 3-dimensional intraoperative spinal navigation. METHODS: Bilateral
      spondylolysis at L3 and L5 with associated spondylolisthesis in a 50-year-old
      male was repaired using the "smiley face" technique. Patient-reported outcomes,
      including the Oswestry Disability Index (ODI) and visual analog scale scores for
      back and leg pain, were assessed preoperatively along with 6 weeks and 4 months
      postoperatively. RESULTS: Postoperative computed tomography imaging showed
      precise screw insertion and rod placement along with stable hardware alignment in
      follow-up imaging. The patient's ODI and lower back visual analog scale scores
      decreased from 25 to 8 and 7.5 to 4, respectively, correlating to an excellent
      outcome on ODI. CONCLUSION: Direct repair and avoidance of fusion is possible and
      can provide good functional outcomes in patients with nonadjacent multilevel
      spondylolysis and associated spondylolisthesis.

PMID- 29054783
TI  - Subfrontal Schwannoma: Case Report and Review of Literature.
AB  - BACKGROUND: Although attributing the origin of schwannomas from the olfactory
      nerve is nearly impossible, if they do not have Schwann cells, intracranial
      supratentorial schwannomas are mainly located in the anterior skull base. CASE
      DESCRIPTION: We present the case of a 46-year-old female who presented with right
      tinnitus, dizziness, and bifrontal headache, progressive, starting 2 years
      before. Imaging studies revealed an incidentally neoplastic, extraaxial,
      homogeneously appearing tumor on the right anterior skull base. The patient
      underwent surgical treatment with total resection of the tumor by a bicoronal
      approach. The histopathologic study reported schwannoma. CONCLUSION: We describe
      this case in detail and discuss the likely origin of this tumor, with a
      concomitant literature review.

PMID- 29054784
TI  - Developing a xenograft human tumor model in immunocompetent mice.
AB  - Animal models are essential to cancer research, but current xenograft models are
      limited in their utility especially due to the lack of an immune system. Here we
      demonstrate that a xenograft tumor model can be developed in immunocompetent mice
      by tolerizing murine fetuses to human tumor cells. A375 human melanoma cells were
      injected into day E14 fetuses and after birth mice were challenged with A375
      cells to determine their ability to develop tumors. Intravenous injections of
      cells resulted in metastatic-like lung tumors, which were verified to be human in
      origin by immunohistochemistry and PCR. These results were replicated with
      several other human tumor types: BxPC3 (human pancreatic adenocarcinoma), MDA-MB
      231 (human breast adenocarcinoma), M21 (human melanoma), and HeLa (human cervical
      adenocarcinoma). Development of an immunocompetent xenograft tumor model would
      allow the further elucidation of the interaction of the immune system with
      therapy in both preclinical research and patient derived xenografts.

PMID- 29054785
TI  - Attention, expectation and iconic memory: A reply to Aru and Bachmann (2017).

PMID- 29054786
TI  - Registered reports for Consciousness and Cognition.

PMID- 29054787
TI  - Lattice Boltzmann simulations of liquid CO2 displacing water in a 2D
      heterogeneous micromodel at reservoir pressure conditions.
AB  - We employed the color-fluid lattice Boltzmann multiphase model to simulate liquid
      CO2 displacing water documented in experiments in a 2D heterogeneous micromodel
      at reservoir pressure conditions. The main purpose is to investigate whether
      lattice Boltzmann simulation can reproduce the CO2 invasion patterns observed in
      these experiments for a range of capillary numbers. Although the viscosity ratio
      used in the simulation matches the experimental conditions, the viscosity of the
      fluids in the simulation is higher than that of the actual fluids used in the
      experiments. Doing so is required to enhance numerical stability, and is a common
      strategy employed in the literature when using the lattice Boltzmann method to
      simulate CO2 displacing water. The simulations reproduce qualitatively similar
      trends of changes in invasion patterns as the capillary number is increased.
      However, the development of secondary CO2 pathways, a key feature of the invasion
      patterns in the simulations and experiments, is found to occur at a much higher
      capillary number in the simulations compared with the experiments. Additional
      numerical simulations were conducted to investigate the effect of the absolute
      value of viscosity on the invasion patterns while maintaining the viscosity ratio
      and capillary number fixed. These results indicate that the use of a high
      viscosity (which significantly reduces the inertial effect in the simulations)
      suppresses the development of secondary CO2 pathways, leading to a different
      fluid distribution compared with corresponding experiments at the same capillary
      number. Therefore, inertial effects are not negligible in drainage process with
      liquid CO2 and water despite the low Reynolds number based on the average
      velocity, as the local velocity can be much higher due to Haines jump events.
      These higher velocities, coupled with the low viscosity of CO2, further amplifies
      the inertial effect. Therefore, we conclude that caution should be taken when
      using proxy fluids that only rely on the capillary number and viscosity ratio in
      both experiment and simulation.

PMID- 29054788
TI  - Pre-exposure prophylaxis is cost-effective for HIV in the UK.

PMID- 29054790
TI  - Narratives of life with long-term low back pain: A follow up interview study.
AB  - BACKGROUND: Long-term low back pain is associated with multiple challenges to a
      person's identity and social position. Despite efforts to understand the
      challenges of low back pain, recovery remains a major problem both personally and
      socially. This indicate a need for a different approach. Although personal
      stories have been used to extend knowledge of issues that relate to low back
      pain, they also make it possible to learn about how people understand themselves
      and their lives. As such, analysis of narratives may provide further insights
      into people's coping processes and novel insights about how best to support them.
      OBJECTIVE: The aim of the study was to analyse personal recovery narratives to
      gain an insight into how people understand themselves and cope with long-term low
      back pain 2-4 years after a bio-psycho-social counselling intervention. STUDY
      DESIGN: Using a Ricoeurian phenomenological-hermeneutic perspective, qualitative
      in-depth interviews were undertaken and interpreted to explore people's
      narratives of long-term recovery after an intervention. METHODS: We interviewed
      25 informants 2-4 years after participating in a counselling intervention for low
      back pain where they were advised to exercise regularly; they were part of the
      intervention group in a randomised clinical trial. The sample included both
      informants who had benefited from the intervention and some who had not. Analysis
      was informed by Ricoeur's interpretation theory. FINDINGS: The informants'
      stories revealed two main narratives regarding themselves and their lives: (1)
      getting on with life without pain, (2) life with continual pain and variations of
      the emplotment. The first included Recovering from low back pain and returning to
      prior lifestyle if possible, Keeping low back pain in check by strict regimes, or
      Developing strategies when low back pain recurs. The second related to Finding a
      way to a functioning everyday life with continual pain while narratives of being
      stuck with low back pain and finding no way out highlight the significance of
      being able to configure a narrative that can support an understanding of the pain
      and how to deal with it to have a functioning life. Furthermore, the health
      professional has a significant role to play in the configuration of narratives.
      CONCLUSIONS: The challenge for people with low back pain was to find ways of
      getting on with life, and this included their ability to configure an
      understandable narrative that opened up for a future, implying new understandings
      of the self and how life could be lived. When healthcare professionals offered
      personal and realistic suggestions to the informants' configuration of narratives
      of life with low back pain, they supported a positive change in the informants'
      ways of coping with their situation. IMPLICATIONS: Health professionals can play
      an important role in low back pain sufferers' configuration of meaningful
      narratives that help in coping with pain and learning about the relationship
      between pain and everyday life.

PMID- 29054789
TI  - Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have
      sex with men in the UK: a modelling study and health economic evaluation.
AB  - BACKGROUND: In the UK, HIV incidence among men who have sex with men (MSM) has
      remained high for several years, despite widespread use of antiretroviral therapy
      and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has
      been shown to be highly effective in preventing further infections in MSM, but
      its cost-effectiveness is uncertain. METHODS: In this modelling study and
      economic evaluation, we calibrated a dynamic, individual-based stochastic model,
      the HIV Synthesis Model, to multiple data sources (surveillance data provided by
      Public Health England and data from a large, nationally representative survey,
      Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis
      (sampling 22 key parameters) along with a range of univariate sensitivity
      analyses to evaluate the introduction of a PrEP programme with sexual event-based
      use of emtricitabine and tenofovir for MSM who had condomless anal sexual
      intercourse in the previous 3 months, a negative HIV test at baseline, and a
      negative HIV test in the preceding year. The main model outcomes were the number
      of HIV infections, quality-adjusted life-years (QALYs), and costs. FINDINGS:
      Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by
      the end of the first year and almost 40 000 by the end of the 15th year, would
      result in a total cost saving (L1.0 billion discounted), avert 25% of HIV
      infections (42% of which would be directly because of PrEP), and lead to a gain
      of 40 000 discounted QALYs over an 80-year time horizon. This result was
      particularly sensitive to the time horizon chosen, the cost of antiretroviral
      drugs (for treatment and PrEP), and the underlying trend in condomless sex.
      INTERPRETATION: This analysis suggests that the introduction of a PrEP programme
      for MSM in the UK is cost-effective and possibly cost-saving in the long term. A
      reduction in the cost of antiretroviral drugs (including the drugs used for PrEP)
      would substantially shorten the time for cost savings to be realised. FUNDING:
      National Institute for Health Research.

PMID- 29054791
TI  - Initial validation of the exercise chronic pain acceptance questionnaire.
AB  - BACKGROUND AND AIMS: Pain acceptance, measured by the chronic pain acceptance
      questionnaire (CPAQ), is related to exercise adherence for those with arthritis.
      The CPAQ measure has 20 items comprising two subscales -- pain willingness and
      activities engagement about pursuing "valued daily activities" despite pain.
      However, exercise is not specified as a valued activity and respondents may be
      considering other activities raising generalizability and strength of prediction
      concerns. METHODS: Accordingly, a modified CPAQ solely for exercise (CPAQ-E) was
      developed to heighten salience to pursuit of exercise in the face of pain. An
      exercising sample with arthritis (N=98) completed the CPAQ-E at baseline and
      exercise 2 weeks later. Exploratory factor analysis of the CPAQ-E was performed
      using Mplus. Regression was used to predict exercise. RESULTS: Analysis revealed
      a two-factor, 14 item model with good psychometric properties reflecting pain
      willingness and activities engagement subscales (chi2=85.695, df=64, p<.037;
      RMSEA=.055; CFI=.967; TLI=.954). Both subscales and the total score positively
      predicted future weekly exercise bouts (range ps from <.05 to <.001). Activities
      engagement predicted future weekly exercise volume (p<.05). CONCLUSIONS: This
      study offers preliminary support for the factorial and predictive validity of the
      CPAQ-E among exercising individuals with arthritis. IMPLICATIONS: This measure
      could help researchers increase the specificity and sensitivity of pain
      acceptance responses to exercising among individuals with arthritis. A more
      sensitive measure might help clinicians interpret patient responses to exercise
      for pain self-management.

PMID- 29054792
TI  - [Management of prostate cancer in patients older than 75 years].
AB  - Prostate cancer is a disease of the elderly men. Prostate cancer in the elderly
      men is often poorly managed and under-treated. The digital rectal examination is
      an effective screening test for elderly prostate cancer patients. In order to
      choose the appropriated therapeutic option, evaluation of life-expectancy is
      essential to offer an optimal individualized treatment. It is essential to take
      into account the patients' aspirations before starting any diagnostic and
      therapeutic approach. Therapeutic options should be adapted in elderly prostate
      cancer patients according to their comorbidities and needs. Elderly patients
      should be included in clinical trials specifically designed for this population.

PMID- 29054793
TI  - Native Vessel CERAB Re-establishes Aorto-iliac Flow Following Occluded
      Aortobifemoral Bypass.

PMID- 29054794
TI  - White Clot Syndrome.

PMID- 29054795
TI  - Topical ALA-PDT as alternative therapeutic option in treatment-recalcitrant
      dermatosis: Report of 4 cases.
AB  - BACKGROUND: Topical Photodynamic therapy (PDT) is widely acknowledged for its
      safety and effectiveness in treating oncologic skin diseases such as basal cell
      carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its
      broad applications in dermatology, this method is a relatively new therapeutic
      option for treating inflammatory/infectious skin diseases. OBJECTIVES: To
      determine whether topical PDT is a safe and effective treatment option in
      treating treatment-recalcitrant dermatosis. OBSERVATIONS: We presented one of
      each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma
      Acuminatum and extramammary Paget's disease, where other treatment options were
      either ineffective or not feasible, then those patients underwent topical PDT and
      showed significant improvement with minimal side effects. CONCLUSIONS: Topical
      PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral
      meatus Condyloma Acuminatum and extramammary Paget's disease, where other
      treatment has shown no or minimal improvement, or in whom ablative or invasive
      procedure is to be avoided or not well tolerated.

PMID- 29054796
TI  - Testosterone, social status and parental care in a cooperatively breeding bird.
AB  - The steroid hormone testosterone not only plays an important role in gamete
      production, but also influences social and aggressive behavior. Testosterone
      varies seasonally, peaking when competition for mates is high and declining
      during parental care. Surprisingly, little is known about how testosterone
      mediates social conflict and parental care behavior in highly social species like
      cooperative breeders, where group members compete for breeding opportunities and
      provide parental or alloparental care. We examined how testosterone differs
      across breeding roles in the tropical cooperatively breeding superb starling,
      Lamprotornis superbus. We determined whether testosterone was elevated in larger
      groups, and whether testosterone was negatively related to total levels of
      parental and alloparental care. We found that male breeders had higher
      testosterone than male helpers and female breeders and helpers during incubation.
      However, breeding males exhibited a significant decline in testosterone from
      incubation to chick rearing, and all individuals had similar levels during the
      chick rearing stage. Additionally, helpers-but not breeders-in large social
      groups had higher testosterone than those in small groups. Finally, testosterone
      was not correlated with nestling provisioning rates during chick rearing,
      suggesting that natural variation in the low levels of testosterone observed
      during periods of high parental care does not affect nestling provisioning.
      Together, these results offer insight into how testosterone is related to
      breeding roles, intra-group conflict, and parental care in a highly social
      species.

PMID- 29054797
TI  - The effects of ovariectomy and lifelong high-fat diet consumption on body weight,
      appetite, and lifespan in female rats.
AB  - In females, ovarian hormones play pivotal roles in metabolic, appetite, and body
      weight regulation. In addition, it has been reported that ovarian hormones also
      affect longevity in some species. Recently, it was found that the consumption of
      a high-fat diet aggravates ovariectomy-associated metabolic dysregulation in
      female rodents. The aim of this study was to investigate the hypothesis that long
      term high-fat diet consumption and ovariectomy interact to worsen body weight
      regulation and longevity in female rats. At 21days of age, female rats were
      weaned and randomly divided into two groups, one of which was given the high-fat
      diet, and the other was supplied with standard chow. At 23weeks of age, each
      group was further divided into ovariectomized and sham-operated groups, and then
      their body weight changes, food intake, and longevity were measured until
      34months of age. The sham - high-fat diet rats exhibited greater body weight
      changes and higher feed efficiency than the sham - standard chow rats. On the
      other hand, the ovariectomized - high-fat diet and ovariectomized - standard chow
      rats displayed similar body weight changes and feed efficiency. The sham - high
      fat diet and ovariectomized - standard chow rats demonstrated similar body weight
      changes and feed efficiency, indicating that the impact of ovariectomy on the
      regulation of body weight and energy metabolism might be similar to that of high
      fat diet. Contrary to our expectations, ovariectomy and high-fat diet consumption
      both had small favorable effects on longevity. As the high-fat diet used in the
      present study not only had a high fat content, but also had a high caloric
      content and a low carbohydrate content compared with the standard chow, it is
      possible that the effects of the high-fat diet on body weight and longevity were
      partially induced by its caloric/carbohydrate contents. These findings indicate
      that the alterations in body weight and energy metabolism induced by ovariectomy
      and high-fat diet might not directly affect the lifespan of female rats.

PMID- 29054798
TI  - The antimicrobial peptide nisin Z induces selective toxicity and apoptotic cell
      death in cultured melanoma cells.
AB  - Reprogramming of cellular metabolism is now considered one of the hallmarks of
      cancer. Most malignant cells present with altered energy metabolism which is
      associated with elevated reactive oxygen species (ROS) generation. This is also
      evident for melanoma, the leading cause of skin cancer related deaths. Altered
      mechanisms affecting mitochondrial bioenergetics pose attractive targets for
      novel anticancer therapies. Antimicrobial peptides have been shown to exhibit
      selective anticancer activities. In this study, the anti-melanoma potential of
      the antimicrobial peptide, nisin Z, was evaluated in vitro. Nisin Z was shown to
      induce selective toxicity in melanoma cells compared to non-malignant
      keratinocytes. Furthermore, nisin Z was shown to negatively affect the energy
      metabolism (glycolysis and mitochondrial respiration) of melanoma cells, increase
      reactive oxygen species generation and cause apoptosis. Results also indicate
      that nisin Z can decrease the invasion and proliferation of melanoma cells
      demonstrating its potential use against metastasis associated with melanoma. As
      nisin Z seems to place a considerable extra burden on the energy metabolism of
      melanoma cells, combination therapies with known anti-melanoma agents may be
      effective treatment options.

PMID- 29054799
TI  - Systematic evaluation of cell-SELEX enriched aptamers binding to breast cancer
      cells.
AB  - The sensitive and specific detection of pathogenic cells is essential in clinical
      diagnostics. To achieve this, molecular tools are required that unequivocally
      recognise appropriate cell surface molecules, such as biomarkers that come along
      with disease onset and progression. Aptamers are short single-stranded
      oligonucleotides that interact with cognate target molecules with high affinity
      and specificity. Within the last years they have gained an increased attention as
      cell-recognition tools. Here, we report a systematic analysis of a cell-SELEX
      procedure, for the identification of aptamers that recognise breast cancer cells.
      Besides a comparison of conventional (Sanger) with high-throughput sequencing
      techniques (next-generation sequencing), three different screening techniques
      have been applied to characterise the binding properties of selected aptamer
      candidates. This method has been found to be beneficial in finding DNA aptamers,
      rarely enriched in the libraries. Finally, four DNA aptamers were identified that
      exhibit broad-spectrum interaction patterns to different cancer cell lines
      derived from solid tumours.

PMID- 29054800
TI  - Aptamer affinity ligands in protein chromatography.
AB  - The present review deals with the place of single chain oligonucleotide ligands
      (aptamers) in affinity chromatography applied to proteins. Aptamers are not the
      only affinity ligands available but they represent an emerging and highly
      promising route that advantageously competes with antibodies in
      immunopurification processes. A historical background of affinity chromatography
      from the beginning of the discipline to the most recent outcomes is first
      presented. Then the focus is centered on aptamers which represent the last step
      so far to the long quest for affinity ligands associating very high specificity,
      availability and strong stability against most harsh cleaning agents required in
      chromatography. Then technologies of ligand selection from large libraries
      followed by the most appropriate chemical grafting approaches are described and
      supported by a number of bibliographic references. Experimental results assembled
      from relevant published paper are reported; they are selected by their practical
      applicability and potential use at large scale. The review concludes with
      specific remarks and future developments that are expected in the near future to
      turn this technology into a large acceptance for preparative applications.

PMID- 29054801
TI  - Why do antifreeze proteins require a solenoid?
AB  - Proteins whose presence prevents water from freezing in living organisms at
      temperatures below 0  degrees C are referred to as antifreeze proteins. This
      group includes molecules of varying size (from 30 to over 300 aa) and variable
      secondary/supersecondary conformation. Some of these proteins also contain
      peculiar structural motifs called solenoids. We have applied the fuzzy oil drop
      model in the analysis of four categories of antifreeze proteins: 1 - very small
      proteins, i.e. helical peptides (below 40 aa); 2 - small globular proteins (40
      100 aa); 3 - large globular proteins (>100 aa) and 4 - proteins containing
      solenoids. The FOD model suggests a mechanism by which antifreeze proteins
      prevent freezing. In accordance with this theory, the presence of the protein
      itself produces an ordering of water molecules which counteracts the formation of
      ice crystals. This conclusion is supported by analysis of the ordering of
      hydrophobic and hydrophilic residues in antifreeze proteins, revealing
      significant variability - from perfect adherence to the fuzzy oil drop model
      through structures which lack a clearly defined hydrophobic core, all the way to
      linear arrangement of alternating local minima and maxima propagating along the
      principal axis of the solenoid (much like in amyloids). The presented model -
      alternative with respect to the ice docking model - explains the antifreeze
      properties of compounds such as saccharides and fatty acids. The fuzzy oil drop
      model also enables differentiation between amyloids and antifreeze proteins.

PMID- 29054802
TI  - Thermodynamic study of aptamers binding to their target proteins.
AB  - Aptamers are nucleic acids that bind to a target molecule with high affinity and
      specificity, which are selected from systematic evolution of ligands by
      exponential enrichment (SELEX). Aptamers feature high affinity and specificity to
      their target molecule and a large structural diversity; biophysical tools,
      together with structural studies, are essential to reveal the mechanism of
      aptamers recognition. Furthermore, understanding the mechanism of action would
      also contribute to their development for therapeutic applications. Isothermal
      titration calorimetry (ITC) is a fast and robust method to study the physical
      basis of molecular interactions. In a single experiment, it provides all
      thermodynamic parameters of a molecular interaction, including dissociation
      constant, Kd; Gibbs free energy change, DeltaG; enthalpy change, DeltaH; entropy
      change, DeltaS; and stoichiometry, N. The development of modern microcalorimeters
      significantly contributed to the expansion of the ITC use in biological systems.
      Therefore, ITC has been applied to the development of small therapeutic agents
      that bind to target proteins and is increasingly being used to study aptamer
      target protein interactions. This review focuses on thermodynamic approaches for
      understanding the molecular principles of aptamer-target interactions.

PMID- 29054803
TI  - Comparison of short-term effects of mobilization with movement and Kinesiotaping
      on pain, function and balance in patellofemoral pain.
AB  - OBJECTIVE: The aim of this study was to compare the short-term effects of
      Mobilization with movement (MWM) and Kinesiotaping (KT) on patients with
      patellofemoral pain (PFP) respect to pain, function and balance. METHODS: Thirty
      five female patients diagnosed with unilateral PFP were assigned into 2 groups.
      The first group (n = 18) received two techniques of MWM intervention (Straight
      Leg-Raise with Traction and Tibial Gliding) while KT was applied to the other
      group (n = 17). Both groups received 4 sessions of treatment twice a week for a
      period of 2 weeks with a 6-week-home exercise program. Pain severity, knee range
      of motion, hamstring flexibility, and physical performance (10-step stair
      climbing test, timed up and go test), Kujala Patellofemoral Pain Scoring and Y
      Balance test were assessed. These outcomes were evaluated before the treatment,
      45 min after the initial treatment, at the end of the 4-session-treatment during
      2-week period and 6 weeks later in both groups. RESULTS: Both treatment groups
      had statistically significant improvements on pain, function and balance (p <
      0.05). Pain at rest (p = 0.008) and the hamstring muscle flexibility (p = 0.027)
      were demonstrated significant improvements in favor of MWM group. CONCLUSIONS:
      Our results demonstrated similar results for both treatment techniques in terms
      of pain, function and balance. The MWM technique with exercise had a short-term
      favorable effect on pain at rest and hamstring muscle flexibility than the KT
      technique with exercise in patients with PFP. LEVEL OF EVIDENCE: Level I,
      therapeutic study.

PMID- 29054804
TI  - Sodium Glucose Cotransporter 2 Inhibition Combined With Cetuximab Significantly
      Reduced Tumor Size and Carcinoembryonic Antigen Level in Colon Cancer Metastatic
      to Liver.

PMID- 29054805
TI  - Factors Predicting Adherence to a Tailored-Dose Adjuvant Treatment on the Basis
      of Geriatric Assessment in Elderly People With Colorectal Cancer: A Prospective
      Study.
AB  - BACKGROUND: Selecting elderly people with colorectal cancer (CRC) for adjuvant
      chemotherapy is challenging. Comprehensive geriatric assessment (CGA) can help by
      classifying them according to their frailty profile. The supposed benefit of
      chemotherapy is on the basis of the rate of treatment adherence. In this study we
      evaluated tolerance and adherence to tailored-dose adjuvant therapy on the basis
      of CGA in a cohort of older patients with high-risk stage II and stage III CRC.
      PATIENTS AND METHODS: This was a prospective study in 193 consecutive patients
      aged 75 years or older. On the basis of CGA results, we classified patients as
      fit, medium fit, or unfit, administering standard therapy, adjusted treatment,
      and best supportive care, respectively. We recorded planned chemotherapy,
      toxicity, and completion of the treatment. A logistic multivariate analysis was
      carried out. RESULTS: Seventeen (15%) of the 141 candidates for chemotherapy (n =
      86 fit and n = 55 medium fit) refused treatment; associated factors included
      polypharmacy (odds ratio [OR], 5.34; 95% confidence interval [CI], 1.55-18.40)
      and rectal location (OR, 5.61; 94% CI, 1.45-21.49). Of the 105 (74%) patients
      receiving chemotherapy, 20 (27%) fit and 4 (13%) medium fit patients experienced
      Grade 3 to 4 toxicity (P = .11) without association to explanatory variables.
      Approximately 55% of patients treated with chemotherapy received at least 80% of
      the planned dose (55% fit and 58% medium fit patients; P = .7). Factors
      associated with completion of chemotherapy were the absence of toxicity (OR,
      7.67; 95% CI, 2.41-24.43) and social support (OR, 2.29; 95% CI, 0.08-1.04).
      CONCLUSION: CGA is useful for selecting elderly patients for adjuvant
      chemotherapy, adapting the dose to their frailty profile, and identifying
      adherence-related factors amenable to modification through CGA-based
      interventions.

PMID- 29054806
TI  - Nutritional physiology of mahi-mahi (Coryphaena hippurus): Postprandial metabolic
      response to different diets and metabolic impacts on swim performance.
AB  - Migratory pelagic fish species, such as the mahi-mahi (Coryphaena hippurus), must
      balance numerous metabolic demands simultaneously in order to survive in a
      challenging oceanic environment. Energetic support for such demands comes from a
      variety of natural prey items in the wild and can come from manufactured
      pelletized feed in captivity. This study quantified postprandial metabolism,
      commonly referred to as specific dynamic action (SDA), over time in adult mahi
      mahi (706+/-25g; 38+/-0.7cm FL) in response to satiation feeding using three
      different natural and manufactured diets. Results indicate that during satiation
      feeding the amount of food ingested is dictated by energy content rather than
      prey mass, regardless of moisture content of the diet. Ingested meal energy did
      not differ significantly across groups (473+/-45kJ), nor did the duration of SDA
      (36+/-2.1h). Satiation feeding levels ranged from 2.9-16.2% bodyweight depending
      on the diet. Peak SDA and SDA magnitude were both significantly decreased in
      response to dry pelletized diet compared to the natural forage diets, despite
      equivalent energy consumption. Swim performance and maximum metabolic rate were
      not impacted significantly in satiation fed fish compared to unfed fish,
      supporting the evidence that mahi-mahi are able to maintain multiple metabolic
      demands at one time without compromising performance.

PMID- 29054807
TI  - Ontogeny of skeletal and cardiac muscle mitochondria oxygen fluxes in two breeds
      of chicken.
AB  - From its earliest days of domestication, the domestic chicken (Gallus gallus
      domesticus) has been selectively bred for specific traits. Decades of genetic
      selection have resulted in significant dissimilarities in metabolism and growth
      between breeds, in particular fast-growing broilers and highly productive layers.
      A chicken develops the capacity to elevate metabolism in response to decreases in
      ambient temperature upon hatching, including well-developed methods of regulating
      thermogenesis. However, a differential timing between incipient endothermic
      capacities of broiler and layer strains exists. Although both broiler and layer
      chicks show the hallmark rapid attainment of endothermic capacity of precocial
      birds, endothermic capacity of broilers matures faster than that of layers. Here
      we characterized changes in morphology and mitochondria physiology during the
      developmental transition as the animals become endothermic. Changes in body mass
      occurred at a faster rate in broilers, with hatching embryos showing significant
      increases over embryonic body mass, while layers did not exhibit significant
      differences in mass until after hatch. Heart and liver both exhibited rapid
      growth upon hatching that occurred with little change in body mass in both
      breeds. Skeletal and cardiac mitochondrial respiration capacity in broilers
      increased from the embryonic stage through hatching. Oxidative phosphorylation
      was more tightly coupled to ATP production in broilers than layer muscles during
      external pipping. By selecting for faster growth and higher meat yield, the
      physiological transition from ectothermy to endothermy was also affected:
      differences in whole-animal, tissue, and organelle responses are evident in these
      two divergent breeds of chicken.

PMID- 29054809
TI  - RE: Author response to letter to the editor from Dr. Galbraith.

PMID- 29054808
TI  - High amylose starch consumption induces obesity in Drosophila melanogaster and
      metformin partially prevents accumulation of storage lipids and shortens lifespan
      of the insects.
AB  - There are very few studies that have directly analyzed the effects of dietary
      intake of slowly digestible starches on metabolic parameters of animals. The
      present study examined the effects of slowly digestible starch with high amylose
      content (referred also as amylose starch) either alone, or in combination with
      metformin on the development, lifespan, and levels of glucose and storage lipids
      in the fruit fly Drosophila melanogaster. Consumption of amylose starch in
      concentrations 0.25-10% did not affect D. melanogaster development, whereas 20%
      starch delayed pupation and reduced the number of larvae that reached the pupal
      stage. Starch levels in larval food, but not in adult food, determined levels of
      triacylglycerides in eight-day-old adult flies. Rearing on diet with 20% starch
      led to shorter lifespan and a higher content of triacylglycerides in the bodies
      of adult flies as compared with the same parameters in flies fed on 4% starch
      diet. Food supplementation with 10mM metformin partly attenuated the negative
      effects of high starch concentrations on larval pupation and decreased
      triacylglyceride levels in adult flies fed on 20% starch. Long-term consumption
      of diets supplemented with metformin and starch decreased lifespan of the
      insects, compared with the diet supplemented with starch only. The data show that
      in Drosophila high starch consumption may induce a fat fly phenotype and
      metformin may partially prevent it.

PMID- 29054810
TI  - Diacetyl and occupational bronchiolitis obliterans: Comments on Rose, CS: Early
      detection, clinical diagnosis and management of lung disease from exposure to
      diacetyl, toxicology (2017), https://doi.org/10.1016/j.tox.2017.03.019.

PMID- 29054811
TI  - Molecular phylogeny of bladderworts: A wide approach of Utricularia
      (Lentibulariaceae) species relationships based on six plastidial and nuclear DNA
      sequences.
AB  - The carnivorous plant genus Utricularia L. (bladderwort) comprises about 240
      species distributed worldwide and is traditionally classified into two subgenera
      (Polypompholyx and Utricularia) and 35 sections, based mainly on general and trap
      morphology. It is one out of the largest carnivorous genera, representing ca. 30%
      of all carnivorous plant species, and is also the most widely distributed.
      According to previous phylogenetic studies, most infrageneric sections are
      monophyletic, but there are several incongruences considering their relationships
      and also the dissenting position of some species as a result of a too few (mostly
      one or two) molecular markers analyzed. Thus, here we present a multilocus
      phylogeny for Utricularia species with a wide taxonomic sampling (78 species and
      115 accessions) based on six plastid (rbcL, matK, rpl20-rps12, rps16, trnL-F) and
      nuclear DNA (ITS region) sequences. The aim is to reconstruct a well-resolved
      tree to propose evolutionary and biogeographic hypotheses for the radiation of
      lineages with inferences about the divergence times of clades using a molecular
      clock approach.

PMID- 29054812
TI  - The impact of inter-annual rainfall variability on African savannas changes with
      mean rainfall.
AB  - Savannas are mixed tree-grass ecosystems whose dynamics are predominantly
      regulated by resource competition and the temporal variability in climatic and
      environmental factors such as rainfall and fire. Hence, increasing inter-annual
      rainfall variability due to climate change could have a significant impact on
      savannas. To investigate this, we used an ecohydrological model of stochastic
      differential equations and simulated African savanna dynamics along a gradient of
      mean annual rainfall (520-780 mm/year) for a range of inter-annual rainfall
      variabilities. Our simulations produced alternative states of grassland and
      savanna across the mean rainfall gradient. Increasing inter-annual variability
      had a negative effect on the savanna state under dry conditions (520 mm/year),
      and a positive effect under moister conditions (580-780 mm/year). The former
      resulted from the net negative effect of dry and wet extremes on trees. In semi
      arid conditions (520 mm/year), dry extremes caused a loss of tree cover, which
      could not be recovered during wet extremes because of strong resource competition
      and the increased frequency of fires. At high mean rainfall (780 mm/year),
      increased variability enhanced savanna resilience. Here, resources were no longer
      limiting and the slow tree dynamics buffered against variability by maintaining a
      stable population during 'dry' extremes, providing the basis for growth during
      wet extremes. Simultaneously, high rainfall years had a weak marginal benefit on
      grass cover due to density-regulation and grazing. Our results suggest that the
      effects of the slow tree and fast grass dynamics on tree-grass interactions will
      become a major determinant of the savanna vegetation composition with increasing
      rainfall variability.

PMID- 29054813
TI  - The effect of sanctions on the evolution of cooperation in linear division of
      labor.
AB  - The evolution of cooperation is an unsolved research topic and has been
      investigated from the viewpoint of not only biology and other natural sciences
      but also social sciences. Much extant research has focused on the evolution of
      cooperation among peers. While, different players belonging to different
      organizations play different social roles, and players playing different social
      roles cooperate together to achieve their goals. We focus on the evolution of
      cooperation in linear division of labor that is defined as follows: a player in
      the i-th role interacts with a player in the i + 1-th role, and a player in the n
      th role achieves their goal (1 <= i < n) if there are n roles in the division of
      labor. We take the industrial waste treatment process as an example for
      illustration. We consider three organizational roles and Bi is the i-th role. The
      player of Bi can choose two strategies: legal treatment or illegal dumping, which
      can be interpreted as cooperation or defection (i = 1-3). With legally required
      treatment, the player of Bj pays a cost to ask the player of Bj+1 to treat the
      waste (j = 1, 2). Then, the cooperator of Bj+1 pays a cost to treat the waste
      properly. With illegal dumping, the player of Bi dumps the waste and does not pay
      any cost (i = 1-3). However, the waste dumped by the defector has negative
      environmental consequences, which all players in all roles suffer from. This
      situation is equivalent to a social dilemma encountered in common-pool resource
      management contexts. The administrative organ in Japan introduces two sanction
      systems to address the illegal dumping problem: the actor responsibility system
      and the producer responsibility system. In the actor responsibility system, if
      players in any role who choose defection are monitored and discovered, they are
      penalized via a fine. However, it is difficult to monitor and detect the
      violators, and this system does not work well. While, in the producer
      responsibility system, the player in B1 is fined if the player cannot hand the
      manifest to the local administrative organ because the players of Bi (i = 1-3)
      who choose defection do not hand the manifest to the player of B1. We analyze
      this situation using the replicator equation. We reveal that (1) the three-role
      model has more empirical credibility than the two-role model including B1 and B3,
      and (2) the producer responsibility system promotes the evolution of cooperation
      more than the system without sanctioning. (3) the actor responsibility system
      does not promote the evolution of cooperation if monitoring and detecting
      defectors is unsuccessful.

PMID- 29054814
TI  - Laparoscopic management of solid pseudo papillary neoplasm of pancreas in
      tertiary care center from south India.
AB  - BACKGROUND: Solid pseudo papillary neoplasm (SPN) of the pancreas which
      predominantly affects young women is a relatively indolent entity with favorable
      prognosis. Resection through minimal access approach helps to achieve better
      short term benefits. The aim of this study is to describe our experience in
      laparoscopic management of this disease. METHODS: A retrospective review of our
      prospectively maintained database revealed that 17 patients with SPN were managed
      with surgical resection between March 2009 and October 2016. The clinical data of
      these patients were then analyzed. RESULTS: Among the 17 cases of SPN, 14 were
      females and 3 were males. The mean age at presentation was 26.1 years (11-46
      years). The most common presenting symptom was an abdominal pain (n = 10; 58.8%).
      A tumor was incidentally detected in 5 patients. The neoplasm was localized in
      the pancreatic head/neck in 6 patients and in the body/tail in 11. The median
      diameter of the tumors was 7.5 cm (2-13 cm). Five patients underwent
      pancreaticoduodenectomy, 10 had distal pancreatectomy, while median
      pancreatectomy or enucleation was performed in one each. All the patients were
      offered laparoscopic surgery; one distal pancreatectomy was converted to open in
      view of bleeding. The median length of stay was 7 days (5-28 days). The patients
      were followed up for a median period of 31 months (3-62 months). CONCLUSION: SPN
      is a rare neoplasm with low malignant potential and has an excellent prognosis.
      In our experience, laparoscopic surgical resection is safe and feasible, even for
      larger lesions.

PMID- 29054816
TI  - An alternative to radiotherapy in consolidation of brain lymphoma.

PMID- 29054815
TI  - Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation
      strategies after high-dose methotrexate-based chemoimmunotherapy in patients with
      primary CNS lymphoma: results of the second randomisation of the International
      Extranodal Lymphoma Study Group-32 phase 2 trial.
AB  - BACKGROUND: The International Extranodal Lymphoma Study Group-32 (IELSG32) trial
      is an international randomised phase 2 study that addresses two key clinical
      questions in the treatment of patients with newly diagnosed primary CNS lymphoma.
      Results of the first randomisation have demonstrated that methotrexate,
      cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction
      combination associated with significantly better outcome compared with the other
      induction combinations tested. Here, we report the results of the second
      randomisation that addresses the efficacy of myeloablative chemotherapy supported
      by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain
      radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based
      chemoimmunotherapy. METHODS: HIV-negative patients (aged 18-70 years) with newly
      diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group
      performance status of 0-3 were randomly assigned to receive four courses of
      methotrexate 3.5 g/m2 on day 1 plus cytarabine 2 g/m2 twice daily on days 2 and 3
      (group A); or the same combination plus two doses of rituximab 375 mg/m2 on days 
      5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus
      thiotepa 30 mg/m2 on day 4 (group C), with the three groups repeating treatment
      every 3 weeks. Patients with responsive or stable disease after induction
      treatment, with adequate autologous peripheral blood stem-cell collection, and
      without persistent iatrogenic side-effects, were eligible for the second
      randomisation between WBRT (photons of 4-10 MeV; five fractions per week;
      fraction size 180 cGy; started within 4 weeks from the last induction course;
      group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m2 on day 
      6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of
      autologous peripheral blood stem cells; group E). A permuted block randomised
      design was adopted for both randomisations, and a computer-generated
      randomisation list was used within each stratum. No masking after assignment to
      intervention was adopted. The primary endpoint was 2-year progression-free
      survival, with induction group and response to induction chemotherapy as
      stratification parameters. Analyses were done on a modified intention-to-treat
      basis. This study is registered with ClinicalTrials.gov, number NCT01011920.
      FINDINGS: Between Feb 19, 2010, and Aug 27, 2014, 227 patients were recruited
      from 53 centres in five countries. 219 of 227 enrolled patients were assessable.
      Of the 122 patients eligible for the second randomisation, 118 patients were
      randomly assigned to WBRT or ASCT (59 patients per group) and constitute the
      study population. WBRT and ASCT were both effective, and achieved the
      predetermined efficacy threshold of at least 40 progression-free survivors at 2
      years among the first 52 patients in both groups D and E. There were no
      significant differences in 2-year progression-free survival between WBRT and
      ASCT: 80% (95% CI 70-90) in group D and 69% (59-79) in group E (hazard ratio
      1.50, 95% CI 0.83-2.71; p=0.17). Both consolidation therapies were well
      tolerated. Grade 4 non-haematological toxicity was uncommon; as expected,
      haematological toxicity was more common in patients treated with ASCT than in
      those who received WBRT. Two toxic deaths (infections) were recorded, both in
      patients who received ASCT. INTERPRETATION: WBRT and ASCT are both feasible and
      effective as consolidation therapies after high-dose methotrexate-based
      chemoimmunotherapy in patients aged 70 years or younger with primary CNS
      lymphoma. The risks and implications of cognitive impairment after WBRT should be
      considered at the time of therapeutic decision. FUNDING: Agenzia Italiana del
      Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Science Foundation.

PMID- 29054817
TI  - Attend or defend? Sex differences in behavioral, autonomic, and respiratory
      response patterns to emotion-eliciting films.
AB  - Sex differences in emotional reactivity have been studied primarily for negative
      but less so for positive stimuli; likewise, sex differences in the
      psychophysiological response-patterning during such stimuli are poorly
      understood. Thus, the present study examined sex differences in response to
      negative/positive and high/low arousing films (classified as threat-, loss-,
      achievement-, and recreation-related, vs. neutral films), while measuring 18
      muscular, autonomic, and respiratory parameters. Sex differences emerged for all
      films, but were most prominent for threat-related films: Despite equivalent
      valence and arousal ratings, women displayed more facial-muscular and respiratory
      responding than men and pronounced sympathetic activation (preejection period,
      other cardiovascular and electrodermal measures), while men showed coactivated
      sympathetic/parasympathetic responding (including increased respiratory sinus
      arrhythmia). This indicates a prototypical threat-related defense response in
      women, while men showed a pattern of sustained orienting, which can be understood
      as a shift toward less threat proximity in the defense cascade model. Clinical
      implications are discussed within a socio-evolutionary framework.

PMID- 29054818
TI  - Parental perception of child weight and inflammation: Perceived overweight is
      associated with higher child c-reactive protein.
AB  - Self-perceived overweight and weight discrimination are associated with
      inflammation in adulthood. We test whether there is an intergenerational
      association of parent perception of child overweight on higher levels of child c
      reactive protein (CRP), a marker of inflammation implicated in stress. Data were
      from the National Health and Nutrition Examination Survey 2005-2014 (N=4988).
      Parents reported their perception of their child's weight; CRP was assayed from
      children's blood samples. Children whose parents perceived them as overweight had
      higher CRP levels than children who were perceived about the right weight;
      perceived underweight was also associated with higher CRP (F(2,4977)=9.23,
      p<.001). These associations were independent of the child's objective weight
      status and waist circumference and held when the sample was limited to children
      with objective overweight and obesity. These results suggest an intergenerational
      transfer of the psychological perception of body weight from parents to the
      inflammatory health of their child.

PMID- 29054820
TI  - The vertebrate habenula.

PMID- 29054819
TI  - High ambient temperature facilitates the acquisition of 3,4
      methylenedioxymethamphetamine (MDMA) self-administration.
AB  - RATIONALE: MDMA alters body temperature in rats with a direction that depends on
      the ambient temperature (TA). The thermoregulatory effects of MDMA and TA may
      affect intravenous self-administration (IVSA) of MDMA but limited prior reports
      conflict. OBJECTIVE: To determine how body temperature responses under high and
      low TA influence MDMA IVSA. METHODS: Male Sprague-Dawley rats were trained to
      IVSA MDMA (1.0mg/kg/infusion; 2-h sessions; FR5 schedule of reinforcement) under
      TA 20 degrees C or 30 degrees C. Radiotelemetry transmitters recorded body
      temperature and activity during IVSA. RESULTS: MDMA intake increased under both
      TA during acquisition, but to a greater extent in the 30 degrees C group. The
      magnitude of hypothermia was initially equivalent between groups but diminished
      over training in the 30 degrees C group. Within-session activity was initially
      lower in the 30 degrees C group, but by the end of acquisition and maintenance,
      activity was similar for both groups. When TA conditions were swapped, the hot
      trained group increased MDMA IVSA under 20 degrees C TA and a modest decrease in
      drug intake was observed in the cold-trained group under 30 degrees C TA.
      Subsequent non-contingent MDMA (1.0-5.0mg/kg, i.v.) found that rats with higher
      MDMA IVSA rates showed blunted hypothermia compared with rats with lower IVSA
      levels; however, within-session activity did not differ by group. High TA
      increased intracranial self-stimulation thresholds in a different group of rats
      and MDMA reduced thresholds below baseline at low, but not high, TA. CONCLUSIONS:
      High TA appears to enhance acquisition of MDMA IVSA through an aversive effect
      and not via thermoregulatory motivation.

PMID- 29054821
TI  - An in vitro experiment to simulate how easy tablets are to swallow.
AB  - The compliance of patients to solid oral dosage forms is strongly conditioned by
      the perceived ease of swallowing, especially in geriatric and pediatric
      populations. This study proposes a method, based on an in vitro model of the
      human oropharyngeal cavity, to study quantitatively the oral phase of human
      swallowing in presence of single or multiple tablets. The dynamics of swallowing
      was investigated varying the size and shape of model tablets and adjusting the
      force applied to the mechanical setup to simulate tongue pressure variations
      among individuals. The evolution of the velocity of the bolus, the oral transit
      time, and the relative position of the solid oral dosage form within the liquid
      bolus were measured quantitatively from high speed camera recordings. Whenever
      the solid dosage forms were big enough to interact with the walls of the in vitro
      oral cavity, a strong effect of the volume of the medication in respect of its
      swallowing velocity was observed, with elongated tablets flowing faster than
      spherical tablets. Conversely, the geometrical properties of the solid oral
      dosage forms did not significantly affect the bolus dynamics when the cross
      section of the tablet was lower than 40% of that of the bolus. The oral phase of
      swallowing multiple tablets was also considered in the study by comparing
      different sizes while maintaining a constant total mass. The predictive power of
      different theories was also evaluated against the experimental results, providing
      a mechanistic interpretation of the dynamics of the in vitro oral phase of
      swallowing. These findings and this approach could pave the way for a better
      design of solid oral medications to address the special needs of children or
      patients with swallowing disorders and could help designing more successful
      sensory evaluations and clinical studies.

PMID- 29054822
TI  - Determining the effects of PEI adsorption on the permeability of 1,2
      dipalmitoylphosphatidylcholine/bis(monoacylglycero)phosphate membranes under
      osmotic stress.
AB  - : Polycations are used for a number of biological applications, including
      antibiotics and gene therapy. One aspect of the use of polycation gene carriers
      such as polyethylenemine (PEI) in gene therapy that is not well understood is
      their ability to escape from the vesicles they are internalized in. Here, in an
      attempt to gain a better understanding of PEI interaction with endosomal lipids
      under osmotic stress, we performed investigations using monolayers and vesicles
      derived from a mixture of neutral and negative lipids (1,2
      dipalmitoylphosphatidylcholine (DPPC) and bis(monoacylglycero)phosphate (BMP),
      respectively). X-ray reflectivity (XR) and Langmuir trough measurements confirmed
      PEI adsorption to the negatively charged membrane. Confocal microscopy imaging
      indicated that PEI adsorption actually increases the overall integrity of the
      DPPC/BMP vesicle against osmotic stresses while also causing overall deformation
      and permeabilization of the lipid membrane, thus leading to leakage of contents
      from the interior of the vesicle. These confocal microscopy observations were
      also supported by data gathered by dynamic light scattering (DLS). STATEMENT OF
      SIGNIFICANCE: In recent decades, researchers have investigated polyamine-based
      gene delivery systems as useful alternatives to viral gene carriers. One step
      that is crucial to the performance of polyamine gene carriers such as
      polyethylenemine (PEI) is escape from late endosomal vesicles during
      intracellular delivery. However, the ability of polyamine/DNA polyplexes to
      effectively escape from endosomes is a little-understood part of the gene therapy
      techniques that use these polyplexes. Here, we performed investigations using
      monolayers and vesicles derived from a mixture of neutral and negative lipids
      (1,2-dipalmitoylphosphatidylcholine (DPPC) and bis(monoacylglycero)phosphate
      (BMP), respectively) as model systems for late endosomes in order to examine the
      interactions of PEI with the DPPC/BMP membranes and study the subsequent effects
      on the stability and permeability of these membranes.

PMID- 29054823
TI  - Characterization and expression analysis of a new small heat shock protein
      Hsp20.4 from Eimeria tenella.
AB  - Small heat shock proteins (sHsps) are ubiquitous and diverse molecular
      chaperones. Found in almost all organisms, they regulate protein refolding and
      protect cells from stress. Until now, no sHsp has been characterized in Eimeria
      tenella. In this study, the novel EtsHsp20.4 gene was cloned from E. tenella by
      rapid amplification of cDNA ends based on a previously identified expressed
      sequence tag. The full-length cDNA was 1019bp in length and contained an open
      reading frame of 558bp that encoded a 185-amino acid polypeptide with a
      calculated molecular weight of 20.4 kDa. The EtsHsp20.4 protein contained a
      distinct HSP20/alpha-crystallin domain that is the key determinant of their
      function as molecular chaperones and belongs to the HSP20 protein family.
      EtsHsp20.4 mRNA levels were higher in sporulated oocysts than in sporozoites or
      second-generation merozoites by real-time quantitative PCR, the transcription of
      EtsHsp20.4 was barely detectable in unsporulated oocysts. Immunolocalization with
      EtsHsp20.4 antibody showed that EtsHsp20.4 was mainly located on the surface of
      sporozoites, first-generation merozoites and second-generation merozoites.
      Following the development of parasites in DF-1 cells, EtsHsp20.4 protein was
      uniformly dispersed in trophozoites, immature schizonts, and mature schizonts.
      Malate dehydrogenase thermal aggregation assays indicated that recombinant
      EtsHsp20.4 had molecular chaperone activity in vitro. These results suggested
      that EtsHsp20.4 might be involved in sporulation in external environments and
      intracellular growth of the parasite in the host.

PMID- 29054824
TI  - 4-Hydroxycinnamic acid protects mice from cigarette smoke-induced pulmonary
      inflammation via MAPK pathways.
AB  - Cigarette smoke (CS) is the main etiological cause of chronic obstructive
      pulmonary disease, the prevalence of which has continuously increased in recent
      years. 4-Hydroxycinnamic acid (HA) is a plant phenolic acid that has anti
      inflammatory activities. In this study, we explored the therapeutic effects of HA
      on airway inflammation caused by CS and lipopolysaccharide (LPS) in mice. The
      animals received 1 h of CS exposure for 7 days and intranasal instillation of LPS
      on day 4. HA (10 and 20 mg/kg) was administered to animals via oral gavage 1 h
      before CS exposure. HA treatment significantly decreased the accumulation of
      inflammatory cells and production of cytokines, including tumor necrosis factor
      alpha, interleukin (IL)-6, and IL-1beta, caused by CS and LPS exposure. After
      histological examination, we observed that HA treatment significantly reduced the
      infiltration of inflammatory cells into lung tissue caused by CS and LPS
      exposure. Furthermore, HA-treated groups showed significantly decreased
      phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal
      kinase, p38, and nuclear factor-kappaB, and activity of cytochrome c oxidase
      subunit-2 caused by CS and LPS. In conclusion, HA effectively suppresses the
      airway inflammatory response induced by CS and LPS exposure, and is closely
      associated with the downregulation of mitogen-activated protein kinases
      signaling.

PMID- 29054825
TI  - Integrative mRNA-miRNA interaction analysis associate with immune response of sea
      cucumber Apostichopus japonicus based on transcriptome database.
AB  - MicroRNAs (miRNAs) constitute a family of endogenous non-coding small RNAs that
      have been demonstrated to be the key effectors in mediating host-pathogen
      interactions. Additionally, high-throughput sequencing provides unexampled
      opportunities to identify the pathogenic mechanism underlying miRNAs. In the
      present study, the target genes of immune-related miRNAs (miR-31, miR-2008, miR
      92a, miR-210 and miR-7) and specific miRNAs (miR-2004) in Echinodermata were
      predicted in silico and validated. Gene ontology (GO) analysis of the target
      genes of these six miRNAs were conducted to further understand the regulatory
      function in the host immunity of Apostichopus japonicus (A. japonicus). Among the
      putative target genes of the six miRNAs, various immune-related targets were
      annotated, such as Nephl, SEC14Ll, p105, GL2, LYS, FNIAL, mTOR, LITAF, SLC44,
      TLR3, Apaf-1, and CNTN4. This work will provide valuable genetic resources to
      understand the interaction of multiple mRNA-miRNAs and the regulation mechanism
      in the anti-bacterial process in the sea cucumber.

PMID- 29054826
TI  - Viral infections in common carp lead to a disturbance of mucin expression in
      mucosal tissues.
AB  - In response to the constant challenge by potential pathogens, external surfaces
      of fish, their skin, gills and intestinal tract, are coated with mucus, a gel
      like substance which largely prevents the entry of pathogens. This mucus gel
      consists mainly of water and mucins, large O-glycosylated proteins, which are
      responsible for forming a gel like mixture. A modulation of the mRNA expression
      of mucins, was described in viral diseases in mammals however there is a
      knowledge gap about the regulation of mucins during viral infection in fish.
      Therefore, novel sequences for common carp mucins were located in an early
      version of the common carp genome and their mRNA expression measured in carp
      under infection with three different viral pathogens: (i) the alloherpesvirus
      cyprinid herpesvirus 3, (ii) the rhabdovirus spring viremia of carp virus and
      (iii) the poxvirus carp edema virus. The results showed a downregulation of mucin
      mRNA expression in gills and gut of common carp under infection with these
      pathogenic viruses. This could be a sign of a severe distress to the mucosal
      tissues in carp which occurs under viral infection. The reduced expression of
      mucins could help explaining the increased susceptibility of virus-infected carp
      to secondary bacterial infection.

PMID- 29054827
TI  - Characterization of a double WAP domain-containing protein from the red swamp
      crayfish Procambarus clarkii.
AB  - Crustaceans express multiple whey acidic protein (WAP) domain containing proteins
      which are components of host immunity. In the present study, a new double WAP
      domain containing protein was identified from red swamp crayfish Procambarus
      clarkii, designated Pc-DWD. The ORF is 387 bp, encoding 128 amino acids
      consisting of signal peptide of 18 residues, and two tandem WAP domains of 38 and
      44 residues. Multiple alignment indicates the presence of conserved motifs in
      both WAP domains, and phylogenetic analysis shows that Pc-DWD is a new member of
      the type-IV crustin family. Pc-DWD transcripts were found most abundantly in
      hemocytes, gills, intestine and heart, and induced by Vibrio anguillarum,
      Staphylococcus aureus and white spot syndrome virus challenge. RNAi knockdown of
      Pc-DWD expression led to increased expression of white spot syndrome virus genes
      and increased crayfish mortality after virus infection. Recombinant Pc-DWD
      exhibited strong protease inhibitory activity towards commercial subtilicin A and
      protease K. Pc-DWD inhibited the crude proteases from V. anguillarum and S.
      aureus cultures and from the crayfish tissue extracts. We infer that Pc-DWD acts
      in crayfish bacterial and viral immunity.

PMID- 29054828
TI  - Cloning and expression study of an IRF4a gene and its two transcript variants in
      turbot, Scophthalmus maximus.
AB  - Interferon regulatory factor 4 (IRF4) is known to be involved in antiviral
      response as well as regulation of functional and developmental processes in
      lymphomyeloid cell lineages in mammals. In this study, the gene of IRF4a and its
      two transcript variants (named IRF4a1 and -2) were cloned from turbot,
      Scophthalmus maximus, the tissue distributions and in vivo immune responsive
      expression patterns of the two transcripts were subsequently examined. The
      Scophthalmus maximus (Sm)IRF4a gene is 8367 nucleotide (nt) in length, consisting
      of eight exons and seven introns. The SmIRF4a1 transcript is 3185 nt long,
      containing an open reading frame (ORF) of 1401 nt that encodes a polypeptide of
      466 amino acids (aa). The SmIRF4a2 transcript is 2265 nt long and identical with
      the SmIRF4a1 from position 1 to 1171, containing an ORF of 1164 nt that encodes a
      truncated protein of 387 aa as a result of a frame shift in exon 6 which
      introduces a premature stop codon. The deduced aa sequence of SmIRF4a1 posses a
      DNA-binding domain (DBD), a nuclear localization signal (NLS), a serine-rich
      domain (SRD) and an IRF association domain (IAD), while SmIRF4a2 lacks the C
      terminal 52 residues of the IAD and the downstream C-terminal extension, instead,
      they are replaced by a 8-aa segment although the three upstream domains are
      intact. Quantitative real-time PCR analysis revealed a broad tissue expression
      for both SmIRF4a1 and -2 with the former showing a significantly higher
      expression in all examined tissues except skin. Expressions of two transcript
      variants after stimulation with polyinosinic:polycytidylic acid [poly(I:C)] and
      turbot reddish body iridovirus (TRBIV) were tested in gills, spleen, head kidney
      and muscle. A two-wave of induced expression pattern was observed for both
      transcripts with either stimulus treatment during a 7-day time course. SmIRF4a2
      responded more promptly to the stimuli and showed a higher level of inducibility
      in the early phase while SmIRF4a1 was strongly detected in the later phase. These
      data suggest an important role of SmIRF4a2 in the fast immune response under a
      background of SmIRF4a1-dominant antiviral response in the IRF4a system of turbot.

PMID- 29054829
TI  - Poly (I:C) and imiquimod induced immune responses and their effects on the
      survival of olive flounder (Paralichthys olivaceus) from viral haemorrhagic
      septicaemia.
AB  - The stimulation of immune genes by polyinosinic:polycytidylic acid (poly (I:C))
      and imiquimod in olive flounder (Paralichthys olivaceus) and their role in
      control of viral haemorrhagic septicaemia virus (VHSV) infection were examined.
      Poly (I:C) (100 MUg/fish) treated olive flounder had very low mortality (5%) post
      VHSV infection, while the imiquimod treated group had 65% and 85% mortality at a
      dose of 100 MUg/fish and 50 MUg/fish, respectively. Though the imiquimod treated
      group had high mortality, it was lower than the untreated group, which had 90%
      mortality. In vivo experiments were conducted to determine effect of the two
      ligands on immune modulation in the head kidney of olive flounder. Poly (I:C)
      activated the immune genes (TLR-3, TLR-7, MDA-5, LGP-2, IRF-3, IRF-7, IL-1beta
      type I IFN and Mx) very early, within 1 d post stimulation, faster and stronger
      than imiquimod. Though Mx levels were enhanced by imiquimod, the host was still
      susceptible to VHSV. The poly (I:C) treated group had a high immune response at
      the time of infection and 1 dpi, though it decreased at later stages. The
      imiquimod treated group and the unstimulated group had a higher immune response
      to VHSV compared to the poly (I:C) treated group. The nucleoprotein copies of
      VHSV were very low in the poly (I:C) treated group but interestingly, were high
      in both untreated and imiquimod treated fish. Thus, host survival from a viral
      infection does not only depend on the quantity of immune response but also the
      time of response. Although imiquimod enhanced immune gene expression in olive
      flounder, a delayed response could be the reason for high mortality to VHS
      compared with poly (I:C), which induced the immune system effectively and
      efficiently to protect the host.

PMID- 29054830
TI  - Epidemiology of Hepatitis C Virus Among People Who Inject Drugs: Protocol for a
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a persistent epidemic among people who
      inject drugs (PWID), and PWID remain as the population experiencing the most
      significant impact of HCV-related morbidity and mortality worldwide. OBJECTIVE:
      The purpose of this systematic review and meta-analysis is to synthesize data on
      the epidemiology of HCV infection among PWID. Our main objectives are to
      characterize the global and regional distribution and determinants of HCV
      infection among PWID. METHODS: A search strategy is conducted that involves both
      the electronic and manual retrievals of literature. Reports are included in this
      review if they present data published between 2006 and 2015 on prevalent or
      incident HCV infection among current or former PWID. Standard meta-analytic
      techniques are performed to synthesize the pooled data and identify correlates of
      HCV infection. RESULTS: The search strategy has been performed, and data
      collection is in progress. Data analysis will follow, and the final results of
      this systematic review/meta-analysis are expected by December 2017. CONCLUSIONS:
      This article describes the protocol for the systematic review and meta-analysis
      of epidemiology of HCV among PWID. We aim to provide synthesized data on HCV
      incidence and prevalence as well as to identify factors associated with HCV
      transmission. Our research contributes empirical evidence that informs scholarly,
      medical, and policy discussions concerning HCV. TRIAL REGISTRATION: PROSPERO
      CRD42016035687; https://www.crd.york.ac.uk/prospero/display_record.asp?
      ID=CRD42016035687 (Archived by WebCite at http://www.webcitation.org/6ttYLn65N).

PMID- 29054831
TI  - Web-Based Information on the Treatment of Tobacco Dependence for Oral Health
      Professionals: Analysis of English-Written Websites.
AB  - BACKGROUND: Studies have been conducted on the content and quality of Web-based
      information for patients who are interested in smoking cessation advice and for
      health care practitioners regarding the content of e-learning programs about
      tobacco cessation. However, to the best of our knowledge, there is no such
      information about the quality of Web-based learning resources regarding smoking
      cessation dedicated to oral health professionals. OBJECTIVE: The aim of this
      study was to identify and evaluate the quality of the content of webpages
      providing information about smoking cessation for oral health care professionals.
      METHODS: Websites were identified using Google and Health on Net (HON) search
      engines using the terms: smoking cessation OR quit smoking OR stop smoking OR 3As
      OR 5As OR tobacco counselling AND dentistry OR dental clinic OR dentist OR dental
      hygienist OR oral health professionals. The first 100 consecutive results of the
      2 search engines were considered for the study. Quality assessment was rated
      using the DISCERN questionnaire, the Journal of the American Medical Association
      (JAMA) benchmarks, and the HON seal. In addition, smoking cessation content on
      each site was assessed using an abbreviated version of the Smoke Treatment Scale
      (STS-C) and the Smoking Treatment Scale-Rating (STS-R). To assess legibility of
      the selected websites, the Flesch Reading Ease (FRES) and the Flesch-Kinkaid
      Reading Grade Level (FKRGL) were used. Websites were also classified into
      multimedia and nonmultimedia and friendly and nonfriendly usability. RESULTS: Of
      the first 200 sites selected (100 of Google and 100 of HON), only 11 met the
      inclusion criteria and mainly belonged to governmental institutions (n=8), with
      the others being prepared by Professional Associations (n=2) and nonprofit
      organizations (n=1). Only 3 were exclusively dedicated to smoking cessation. The
      average score obtained with the DISCERN was 3.0, and the average score in the
      FKRGL and FRES was 13.31 (standard deviation, SD 3.34) and 40.73 (SD 15.46),
      respectively. Of the 11 websites evaluated, none achieved all the four JAMA
      benchmarks. The mean score of STS-R among all the websites was 2.81 (SD 0.95) out
      of 5. A significant strong positive correlation was obtained between the DISCERN
      mean values and the STS-R (R=.89, P=.01). CONCLUSIONS: The mean quality of
      webpages with information for oral health care professionals about smoking
      cessation is low and displayed a high heterogeneity. These webpages are also
      difficult to read and often lack multimedia resources, which further limits their
      usefulness.

PMID- 29054832
TI  - Sampling Key Populations for HIV Surveillance: Results From Eight Cross-Sectional
      Studies Using Respondent-Driven Sampling and Venue-Based Snowball Sampling.
AB  - BACKGROUND: In using regularly collected or existing surveillance data to
      characterize engagement in human immunodeficiency virus (HIV) services among
      marginalized populations, differences in sampling methods may produce different
      pictures of the target population and may therefore result in different
      priorities for response. OBJECTIVE: The objective of this study was to use
      existing data to evaluate the sample distribution of eight studies of female sex
      workers (FSW) and men who have sex with men (MSM), who were recruited using
      different sampling approaches in two locations within Sub-Saharan Africa:
      Manzini, Swaziland and Yaounde, Cameroon. METHODS: MSM and FSW participants were
      recruited using either respondent-driven sampling (RDS) or venue-based snowball
      sampling. Recruitment took place between 2011 and 2016. Participants at each
      study site were administered a face-to-face survey to assess sociodemographics,
      along with the prevalence of self-reported HIV status, frequency of HIV testing,
      stigma, and other HIV-related characteristics. Crude and RDS-adjusted prevalence
      estimates were calculated. Crude prevalence estimates from the venue-based
      snowball samples were compared with the overlap of the RDS-adjusted prevalence
      estimates, between both FSW and MSM in Cameroon and Swaziland. RESULTS: RDS
      samples tended to be younger (MSM aged 18-21 years in Swaziland: 47.6% [139/310]
      in RDS vs 24.3% [42/173] in Snowball, in Cameroon: 47.9% [99/306] in RDS vs 20.1%
      [52/259] in Snowball; FSW aged 18-21 years in Swaziland 42.5% [82/325] in RDS vs
      8.0% [20/249] in Snowball; in Cameroon 15.6% [75/576] in RDS vs 8.1% [25/306] in
      Snowball). They were less educated (MSM: primary school completed or less in
      Swaziland 42.6% [109/310] in RDS vs 4.0% [7/173] in Snowball, in Cameroon 46.2%
      [138/306] in RDS vs 14.3% [37/259] in Snowball; FSW: primary school completed or
      less in Swaziland 86.6% [281/325] in RDS vs 23.9% [59/247] in Snowball, in
      Cameroon 87.4% [520/576] in RDS vs 77.5% [238/307] in Snowball) than the snowball
      samples. In addition, RDS samples indicated lower exposure to HIV prevention
      information, less knowledge about HIV prevention, limited access to HIV
      prevention tools such as condoms, and less-reported frequency of sexually
      transmitted infections (STI) and HIV testing as compared with the venue-based
      samples. Findings pertaining to the level of disclosure of sexual practices and
      sexual practice-related stigma were mixed. CONCLUSIONS: Samples generated by RDS
      and venue-based snowball sampling produced significantly different prevalence
      estimates of several important characteristics. These findings are tempered by
      limitations to the application of both approaches in practice. Ultimately, these
      findings provide further context for understanding existing surveillance data and
      how differences in methods of sampling can influence both the type of individuals
      captured and whether or not these individuals are representative of the larger
      target population. These data highlight the need to consider how program coverage
      estimates of marginalized populations are determined when characterizing the
      level of unmet need.

PMID- 29054833
TI  - Pregnant Women's Perceptions of the Risks and Benefits of Disclosure During Web
      Based Mental Health E-Screening Versus Paper-Based Screening: Randomized
      Controlled Trial.
AB  - BACKGROUND: Pregnant women's perceptions of the risks and benefits during mental
      health screening impact their willingness to disclose concerns. Early research in
      violence screening suggests that such perceptions may vary by mode of screening,
      whereby women view the anonymity of e-screening as less risky than other
      approaches. Understanding whether mode of screening influences perceptions of
      risk and benefit of disclosure is important in screening implementation.
      OBJECTIVE: The objective of this randomized controlled trial was to compare the
      perceptions of pregnant women randomized to a Web-based screening intervention
      group and a paper-based screening control group on the level of risk and benefit
      they perceive in disclosing mental health concerns to their prenatal care
      provider. A secondary objective was to identify factors associated with women's
      perceptions of risk and benefit of disclosure. METHODS: Pregnant women recruited
      from maternity clinics, hospitals, and prenatal classes were computer-randomized
      to a fully automated Web-based e-screening intervention group or a paper-based
      control. The intervention group completed the Antenatal Psychosocial Health
      Assessment and the Edinburgh Postnatal Depression Scale on a computer tablet,
      whereas the control group completed them on paper. The primary outcome was
      women's perceptions of the risk and benefits of mental health screening using the
      Disclosure Expectations Scale (DES). A completer analysis was conducted.
      Statistical significance was set at P<.05. We used t tests to compare the means
      of the risk and benefit subscales between groups. RESULTS: Of the 675 eligible
      women approached, 636 (94.2%) agreed to participate and were randomized to the
      intervention (n=305) and control (n=331) groups. There were no significant
      baseline differences between groups. The mode of screening was not associated
      with either perceived risk or benefit of screening. There were no differences in
      groups in the mean scores of the risk and benefit of disclosure subscales. Over
      three-quarters of women in both intervention and control groups perceived that
      mental health screening was beneficial. However, 43.1% (272/631) of women in both
      groups reported feeling very, moderately, or somewhat vulnerable during mental
      health screening. We found that women of low income, those treated previously for
      depression or anxiety, and those pregnant with their first child were more likely
      to perceive greater risk. However, these associations were very small.
      CONCLUSIONS: Pregnant women in both the e-screening and paper-based screening
      groups perceived benefit and risk of disclosure similarly, suggesting that
      providers can implement the mode of screening that is most ideal for their
      clinical setting. Regardless of the mode of screening, a substantial number of
      women reported feeling vulnerable during mental health screening, highlighting
      the importance of the need to reduce women's vulnerability throughout the
      screening process with strategies such as addressing women's concerns, explaining
      the rationale for screening, and discussing how results will be used. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01899534;
      https://clinicaltrials.gov/ct2/show/NCT01899534 (Archived by WebCite at
      http://www.webcitation.org/6tRKtGC4M).

PMID- 29054834
TI  - Evaluation of Web-Based Continuing Professional Development Courses: Aggregate
      Mixed-Methods Model.
AB  - BACKGROUND: Many continuing professional development (CPD) Web-based programs are
      not explicit about underlying theory and fail to demonstrate impact. OBJECTIVE:
      The aim of this study was to develop and apply an aggregate mixed-methods
      evaluation model to describe the paradigm, theoretical framework, and
      methodological approaches used to evaluate a CPD course in tobacco dependence
      treatment, the Training Enhancement in Applied Cessation Counseling and Health
      (TEACH) project. METHODS: We evaluated the effectiveness of the 5-week TEACH Web
      based Core Course in October 2015. The model of evaluation was derived using a
      critical realist lens to incorporate a dimension of utilitarian to intuitionist
      approaches. In addition, we mapped our findings to models described by
      Fitzpatrick et al, Moore et al, and Kirkpatrick. We used inductive and deductive
      approaches for thematic analysis of qualitative feedback and dependent samples t
      tests for quantitative analysis. RESULTS: A total of 59 participants registered
      for the course, and 48/59 participants (81%) completed all course requirements.
      Quantitative analysis indicated that TEACH participants reported (1) high ratings
      (4.55/5, where 5=best/excellent) for instructional content and overall
      satisfaction of the course (expertise and consumer-oriented approach), (2) a
      significant increase (P ?.001) in knowledge and skills (objective-oriented
      approach), and (3) high motivation (78.90% of participants) to change and sustain
      practice change (management-oriented approach). Through the intuitionist lens,
      inductive and deductive qualitative thematic analysis highlighted three central
      themes focused on (1) knowledge acquisition, (2) recommendations to enhance
      learning for future participants, and (3) plans for practice change in the
      formative assessment, and five major themes emerged from the summative
      assessment: (1) learning objectives, (2) interprofessional collaboration, (3)
      future topics of relevance, (4) overall modification, and (5) overall
      satisfaction. CONCLUSIONS: In the current aggregate model to evaluate CPD Web
      based training, evaluators have been influenced by different paradigms,
      theoretical lenses, methodological approaches, and data collection methods to
      address and respond to different needs of stakeholders impacted by the training
      outcomes.

PMID- 29054835
TI  - A Strategy to Reduce Critical Cardiorespiratory Alarms due to Intermittent
      Enteral Feeding of Preterm Neonates in Intensive Care.
AB  - BACKGROUND: Many preterm infants require enteral feeding as they cannot
      coordinate sucking, swallowing, and breathing. In enteral feeding, milk feeds are
      delivered through a small feeding tube passed via the nose or mouth into the
      stomach. Intermittent milk feeds may either be administered using a syringe to
      gently push milk into the infant's stomach (push feed) or milk can be poured into
      a syringe attached to the tube and allowed to drip in by gravity (gravity feed).
      This practice of enteral feeding is common in neonatal intensive care units.
      There is, however, no evidence in the literature to recommend the use of one
      method of feeding over the other. OBJECTIVE: The aim of this study was to
      investigate which of the two methods of feeding is physiologically better
      tolerated by infants, as measured by the incidence of critical cardiorespiratory
      alarms during and immediately after feeding. METHODS: We conducted a
      prospectively designed observational study with records of all feeding episodes
      in infants of gestational age less than 30 weeks at birth and with a minimum
      enteral intake of 100 mL/kg/day. In total, 2140 enteral feeding episodes were
      noted from 25 infants over 308 infant-days with records for several
      characteristics of the infants (eg, gestational age), feeding (eg, the position
      of infants), and of nursing-care events before feeding (eg, diapering). Logistic
      regression with mixed effects was used to model cardiorespiratory alarms for the
      push and gravity methods of feeding. RESULTS: After adjustments were made for all
      confounding variables, the position of infants was found to be statistically
      significant in changing the outcome of critical alarms for the two methods of
      feeding (P=.02). For infants in the lateral position, push feeds led to 40% more
      instances of one or more critical cardiorespiratory alarms in comparison with the
      gravity method. Both methods of feeding created a statistically comparable number
      of alarms for infants in the prone position. CONCLUSIONS: This study provides
      objective data that may assist in optimizing enteral feeding protocols for
      premature infants. The incidence of critical cardiorespiratory alarms for infants
      in the lateral position can be lowered by the use of gravity instead of push
      feeding. No differences were observed between the two types of feeding when
      infants were in the prone position.

PMID- 29054836
TI  - Formative Assessment: Design of a Web-Connected Sedentary Behavior Intervention
      for Females.
AB  - BACKGROUND: Sedentary behavior (SB) is a significant risk factor for heart
      disease, diabetes, obesity, and early mortality, particularly among women, and
      the health consequences associated with SB are independent of physical activity
      status. Interventions utilizing wearable technologies can improve SB, but their
      effectiveness is influenced by individual preferences, device engagement
      strategies, and technological features, which may affect user compliance.
      Gathering a priori insight from target populations on their preferences for
      program tools and strategies may assist researchers in identifying effective
      methods to improve the efficacy of SB interventions. OBJECTIVE: The objective of
      this study was to (1) explore the likeability (likes and dislikes) and usability
      (engagement intentions and navigation) of a wearable device (Movband) and its
      accompanying website (dashboard), (2) examine social incentive preferences
      (teammates), and (3) assess the feasibility (participants' experiences during an
      activity-monitoring period) of these tools for use in an intervention to reduce
      SB in girls and women. METHODS: A total of 9 girls (mean age: 8.9 years, standard
      deviation [SD] 1.1 years) and 11 college-aged women (mean age: 22.6 years, SD 3.2
      years) participated in this study. Separate focus groups were held for girls and
      women, and all participants attended one before and the other following a 7-day
      activity-monitoring period. During the focus groups, participants were prompted
      with questions to address the study aims, and the nominal group technique was
      used to compile lists of group-specific preferences for the activity-monitoring
      system. The top three ranking likes and dislikes were reverse coded to determine
      likeability. RESULTS: The top-ranking responses for the girls and women were the
      following: visual display of movements and ease of navigation (dashboard like),
      boring to look at and no calorie-tracking function (dashboard dislike), backlight
      and long battery life (Movband like), and color and not waterproof (tied for
      girls) and vertical time display (Movband dislike). Additionally, participants
      identified several aesthetic preferences and functional limitations. At the
      second focus group visit, the majority of the participants self-reported less SB
      during the previous week. Objective data from the activity-monitoring period
      revealed that the average steps per day for girls and women were 12,373.4 (SD
      2617.6) and 8515.8 (SD 3076.7), respectively. CONCLUSIONS: These results suggest
      that the girls and women liked many features of the Movband and dashboard.
      However, several dislikes were mentioned, which may negatively influence
      compliance and the effectiveness of the activity-monitoring system and require
      improvements before using in an SB intervention.

PMID- 29054838
TI  - A new indemnity scheme for GPs.

PMID- 29054837
TI  - Altered metabolic landscape in IDH-mutant gliomas affects phospholipid, energy,
      and oxidative stress pathways.
AB  - Heterozygous mutations in NADP-dependent isocitrate dehydrogenases (IDH) define
      the large majority of diffuse gliomas and are associated with hypermethylation of
      DNA and chromatin. The metabolic dysregulations imposed by these mutations,
      whether dependent or not on the oncometabolite D-2-hydroxyglutarate (D2HG), are
      less well understood. Here, we applied mass spectrometry imaging on intracranial
      patient-derived xenografts of IDH-mutant versus IDH wild-type glioma to profile
      the distribution of metabolites at high anatomical resolution in situ This
      approach was complemented by in vivo tracing of labeled nutrients followed by
      liquid chromatography-mass spectrometry (LC-MS) analysis. Selected metabolites
      were verified on clinical specimen. Our data identify remarkable differences in
      the phospholipid composition of gliomas harboring the IDH1 mutation. Moreover, we
      show that these tumors are characterized by reduced glucose turnover and a lower
      energy potential, correlating with their reduced aggressivity. Despite these
      differences, our data also show that D2HG overproduction does not result in a
      global aberration of the central carbon metabolism, indicating strong adaptive
      mechanisms at hand. Intriguingly, D2HG shows no quantitatively important glucose
      derived label in IDH-mutant tumors, which suggests that the synthesis of this
      oncometabolite may rely on alternative carbon sources. Despite a reduction in
      NADPH, glutathione levels are maintained. We found that genes coding for key
      enzymes in de novo glutathione synthesis are highly expressed in IDH-mutant
      gliomas and the expression of cystathionine-beta-synthase (CBS) correlates with
      patient survival in the oligodendroglial subtype. This study provides a detailed
      and clinically relevant insight into the in vivo metabolism of IDH1-mutant
      gliomas and points to novel metabolic vulnerabilities in these tumors.

PMID- 29054839
TI  - Incremental Prognostic Utility of Left Ventricular Global Longitudinal Strain in
      Hypertrophic Obstructive Cardiomyopathy Patients and Preserved Left Ventricular
      Ejection Fraction.
AB  - BACKGROUND: In obstructive hypertrophic cardiomyopathy patients with preserved
      left ventricular (LV) ejection fraction, we sought to determine whether LV global
      longitudinal strain (LV-GLS) provided incremental prognostic utility. METHODS AND
      RESULTS: We studied 1019 patients with documented hypertrophic cardiomyopathy
      (mean age, 50+/-12 years; 63% men) evaluated at our center between 2001 and 2011.
      We excluded age <18 years, maximal LV outflow tract gradient <30 mm Hg, bundle
      branch block or atrial fibrillation, past pacemaker/cardiac surgery, including
      myectomy/alcohol ablation, and obstructive coronary artery disease. Average
      resting LV-GLS was measured offline on 2-, 3-, 4-chamber views using Velocity
      Vector Imaging (Siemens, Malvern, PA). Outcome was a composite of cardiac death
      and appropriate internal defibrillator (implantable cardioverter defibrillator)
      discharge. Maximal LV thickness, LV ejection fraction, indexed left atrial
      dimension, rest and maximal LV outflow tract gradient, and LV-GLS were 2.0+/-0.2
      cm, 62+/-4%, 2.2+/-4 cm/m2, 52+/-42 mm Hg, 103+/-36 mm Hg, and -13.6+/-4%. During
      9.4+/-3 years of follow-up, 668 (66%), 166 (16%), and 122 (20%), respectively,
      had myectomy, atrial fibrillation, and implantable cardioverter defibrillator
      implantation, whereas 69 (7%) had composite events (62 cardiac deaths).
      Multivariable competing risk regression analysis revealed that higher age
      (subhazard ratio, 1.04 [1.02-1.07]), AF during follow-up (subhazard ratio, 1.39
      [1.11-1.69]), and worsening LV-GLS (subhazard ratio, 1.11 [1.05-1.22]) were
      associated with worse outcomes, whereas myectomy (subhazard ratio, 0.44 [0.25
      0.72]) was associated with improved outcomes (all P<0.01). Sixty-one percent of
      events occurred in patients with LV-GLS worse than median (-13.7%). CONCLUSIONS:
      In obstructive hypertrophic cardiomyopathy patients with preserved LV ejection
      fraction, abnormal LV-GLS was independently associated with higher events,
      whereas myectomy was associated with improved outcomes.

PMID- 29054841
TI  - Compelling Benefit of Soluble Suppression of Tumorigenicity-2 in Post-Myocardial
      Infarction Estimation of Risk: The Time Is Right for Its Routine Use in the
      Clinic.

PMID- 29054840
TI  - Contemporary Risk Stratification After Myocardial Infarction in the Community:
      Performance of Scores and Incremental Value of Soluble Suppression of
      Tumorigenicity-2.
AB  - BACKGROUND: Current American Heart Association/American College of Cardiology
      guidelines recommend the GRACE (Global Registry of Acute Coronary Events) and
      TIMI (Thrombolysis in Myocardial Infarction) scores to assess myocardial
      infarction (MI) prognosis. Changes in the epidemiological characteristics of MI
      and the availability of new biomarkers warrant an assessment of the performance
      of these scores in contemporary practice. We assessed the following: (1) the
      performance of GRACE and TIMI to predict 1-year mortality in a cohort of patients
      stratified by ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI) and (2) the
      incremental discriminatory power of soluble suppression of tumorigenicity-2, a
      myocardial fibrosis biomarker. METHODS AND RESULTS: Olmsted County, Minnesota,
      residents with incident MI (N=1401) were recruited prospectively from November 1,
      2002 to December 31, 2012 (mean age, 67 years; 61% men; 79% with NSTEMI).
      Baseline data were used to calculate risk scores; soluble suppression of
      tumorigenicity-2 was measured in stored plasma samples obtained at index MI. C
      statistics adapted to survival data were used to assess the discriminatory power
      of the risk scores and the improvement gained by adding other markers. During the
      first year of follow-up, 190 patients (14%) died. The discriminatory performance
      to predict death was reasonable for GRACE and poor for TIMI, and was generally
      worse in those with NSTEMI versus those with STEMI. In people with NSTEMI,
      sequential addition of comorbidities and soluble suppression of tumorigenicity-2
      substantially improved the c-statistic over GRACE (from 0.78 to 0.80 to 0.84) and
      TIMI (from 0.61 to 0.73 to 0.81), respectively (all P<=0.05). CONCLUSIONS:
      Guideline-recommended scores for risk assessment after MI underperform in
      contemporary community patients, particularly those with NSTEMI, which now
      represents most infarcts. Incorporating comorbidities and soluble suppression of
      tumorigenicity-2 substantially improves risk prediction, thereby delineating
      opportunities to improve clinical care.

PMID- 29054842
TI  - Acute Biventricular Mechanical Circulatory Support for Cardiogenic Shock.
AB  - BACKGROUND: Biventricular failure is associated with high in-hospital mortality.
      Limited data regarding the efficacy of biventricular Impella axial flow catheters
      (BiPella) support for biventricular failure exist. The aim of this study was to
      explore the clinical utility of percutaneously delivered BiPella as a novel acute
      mechanical support strategy for patients with cardiogenic shock complicated by
      biventricular failure. METHODS AND RESULTS: We retrospectively analyzed data from
      20 patients receiving BiPella for biventricular failure from 5 tertiary-care
      hospitals in the United States. Left ventricular support was achieved with an
      Impella 5.0 (n=8), Impella CP (n=11), or Impella 2.5 (n=1). All patients received
      the Impella RP for right ventricular (RV) support. BiPella use was recorded in
      the setting of acute myocardial infarction (n=11), advanced heart failure (n=7),
      and myocarditis (n=2). Mean flows achieved were 3.4+/-1.2 and 3.5+/-0.5 for left
      ventricular and RV devices, respectively. Total in-hospital mortality was 50%. No
      intraprocedural mortality was observed. Major complications included limb
      ischemia (n=1), hemolysis (n=6), and Thrombolysis in Myocardial Infarction major
      bleeding (n=7). Compared with nonsurvivors, survivors were younger, had a lower
      number of inotropes or vasopressors used before BiPella, and were more likely to
      have both devices implanted simultaneously during the same procedure. Compared
      with nonsurvivors, survivors had lower pulmonary artery pressures and RV stroke
      work index before BiPella. Indices of RV afterload were quantified for 14
      subjects. Among these patients, nonsurvivors had higher pulmonary vascular
      resistance (6.8; 95% confidence interval [95% CI], 5.5-8.1 versus 1.9; 95% CI,
      0.8-3.0; P<0.01), effective pulmonary artery elastance (1129; 95% CI, 876-1383
      versus 458; 95% CI, 263-653; P<0.01), and lower pulmonary artery compliance (1.5;
      95% CI, 0.9-2.1 versus 2.7; 95% CI, 1.8-3.6; P<0.05). CONCLUSIONS: This is the
      largest, retrospective analysis of BiPella for cardiogenic shock. BiPella is
      feasible, reduces cardiac filling pressures and improves cardiac output across a
      range of causes for cardiogenic shock. Simultaneous left ventricular and RV
      device implantation and lower RV afterload may be associated with better outcomes
      with BiPella. Future prospective studies of BiPella for cardiogenic shock are
      required.

PMID- 29054843
TI  - Contribution of Extra-Cardiac Cells in Murine Heart Valves is Age-Dependent.
AB  - BACKGROUND: Heart valves are dynamic structures that open and close over 100 000
      times a day to maintain unidirectional blood flow during the cardiac cycle.
      Function is largely achieved by highly organized layers of extracellular matrix
      that provide the necessary biomechanical properties. Homeostasis of valve
      extracellular matrix is mediated by valve endothelial and interstitial cell
      populations, and although the embryonic origins of these cells are known, it is
      not clear how they are maintained after birth. The goal of this study is to
      examine the contribution of extracardiac cells to the aortic valve structure with
      aging using lineage tracing and bone marrow transplantation approaches. METHODS
      AND RESULTS: Immunohistochemistry and fate mapping studies using CD45-Cre mice
      show that the contribution of hematopoietic-derived cells to heart valve
      structures begins during embryogenesis and increases with age. Short-term (6
      weeks), CD45-derived cells maintain CD45 expression and the majority coexpress
      monocyte markers (CD11b), whereas coexpression with valve endothelial (CD31) and
      interstitial (Vimentin) cell markers were infrequent. Similar molecular
      phenotypes are observed in heart valves of irradiated donor mice following
      transplantation of whole bone marrow cells, and engraftment efficiency in this
      tissue is age-dependent. CONCLUSIONS: Findings from this study demonstrate that
      the percentage of CD45-positive extracardiac cells reside within endothelial and
      interstitial regions of heart valve structures increases with age. In addition,
      bone transplantation studies show that engraftment is dependent on the age of the
      donor and age of the tissue environment of the recipient. These studies create a
      foundation for further work defining the role of extracardiac cells in
      homeostatic and diseased heart valves.

PMID- 29054844
TI  - The Impact of De-escalation of Antianginal Medications on Health Status After
      Percutaneous Coronary Intervention.
AB  - BACKGROUND: Antianginal medications (AAMs) can be perceived to be less important
      after percutaneous coronary intervention (PCI) and may be de-escalated after
      revascularization. We examined the frequency of AAM de-escalation at discharge
      post-PCI and its association with follow-up health status. METHODS AND RESULTS:
      In a 10-center PCI registry, the Seattle Angina Questionnaire was assessed before
      and 6 months post-PCI. AAM de-escalation was defined as fewer AAMs at discharge
      versus admission or >25% absolute dose decrease. Of 2743 PCI patients (70% male),
      AAM were de-escalated, escalated, and unchanged in 299 (11%), 714 (26%), and 1730
      (63%) patients, respectively. Patients whose AAM were de-escalated were more
      likely to report angina at 6 months, compared with unchanged or escalated AAM
      (34% versus 24% versus 21%; P<0.001). The association of AAM de-escalation with
      health status was examined using multivariable models adjusting for the predicted
      risk of post-PCI angina, completeness of revascularization, and the interaction
      of AAM de-escalation*completeness of revascularization. There was a significant
      interaction between AAM de-escalation and completeness of revascularization
      (P<0.001), suggesting that AAM de-escalation was associated with greater
      impairment of health status among patients with incomplete revascularization. In
      patients with incomplete revascularization, de-escalation of AAM at discharge was
      associated with 43% increased angina risk (relative risk, 1.43; 95% confidence
      interval, 1.26-1.63) and worse angina-related health status at 6 months post-PCI.
      CONCLUSIONS: De-escalation of AAM occurs in 1 in 10 patients post-PCI, and it is
      associated with an increased risk of angina and worse health status, particularly
      among those with incomplete revascularization.

PMID- 29054845
TI  - Does Moderate Drinking Increase the Risk of Atrial Fibrillation? The Norwegian
      HUNT (Nord-Trondelag Health) Study.
AB  - BACKGROUND: Compelling evidence suggests that excessive alcohol consumption
      increases the risk of atrial fibrillation (AF), but the effect of light-moderate
      alcohol consumption is less certain. We investigated the association between
      alcohol consumption within recommended limits and AF risk in a light-drinking
      population. METHODS AND RESULTS: Among 47 002 participants with information on
      alcohol consumption in a population-based cohort study in Norway, conducted from
      October 2006 to June 2008, 1697 validated AF diagnoses were registered during the
      8 years of follow-up. We used Cox proportional hazard models with fractional
      polynomials to analyze the association between alcohol intake and AF. Population
      attributable risk for drinking within the recommended limit (ie, at most 1 drink
      per day for women and 2 drinks per day for men without risky drinking) compared
      with nondrinking was also calculated. The average alcohol intake was 3.8+/-4.8
      g/d. The adjusted hazard ratio for AF was 1.38 (95% confidence interval, 1.06
      1.80) when we compared participants consuming >7 drinks per week with abstainers.
      When we modeled the quantity of alcohol intake as a continuous variable, the risk
      increased in a curvilinear manner. It was higher with heavier alcohol intake, but
      there was virtually no association at <1 drink per day for women and <2 drinks
      per day for men in the absence of risky drinking. The population attributable
      risk among nonrisky drinkers was 0.07% (95% confidence interval, -0.01% to
      0.13%). CONCLUSIONS: Although alcohol consumption was associated with a
      curvilinearly increasing risk of AF in general, the attributable risk of alcohol
      consumption within recommended limits among participants without binge or problem
      drinking was negligible in this population.

PMID- 29054847
TI  - Burden of Proof-When Is Kidney Disease Attributable to Diabetes?

PMID- 29054846
TI  - Diabetes and CKD in the United States Population, 2009-2014.
AB  - BACKGROUND AND OBJECTIVES: Diabetes is an important cause of CKD. However, among
      people with diabetes, it is unclear to what extent CKD is attributable to
      diabetes itself versus comorbid conditions, such as advanced age and
      hypertension. We examined associations of diabetes with clinical manifestations
      of CKD independent of age and BP and the extent to which diabetes contributes to
      the overall prevalence of CKD in the United States. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We performed a cross-sectional study of 15,675
      participants in the National Health and Nutrition Examination Surveys from 2009
      to 2014. Diabetes was defined by use of glucose-lowering medications or
      hemoglobin A1c >=6.5%. eGFR was calculated using the CKD Epidemiology
      Collaboration formula, and albumin-to-creatinine ratio was measured in single
      void urine samples. We calculated the prevalence of CKD manifestations by
      diabetes status as well as prevalence ratios, differences in prevalence, and
      prevalence attributable to diabetes using binomial and linear regression,
      incorporating data from repeat eGFR and urine albumin-to-creatinine ratio
      measurements to estimate persistent disease. RESULTS: For participants with
      diabetes (n=2279) versus those without diabetes (n=13,396), the estimated
      prevalence of any CKD (eGFR<60 ml/min per 1.73 m2; albumin-to-creatinine ratio
      >=30 mg/g, or both) was 25% versus 5.3%, respectively; albumin-to-creatinine
      ratio >=30 mg/g was 16% versus 3.0%, respectively; albumin-to-creatinine ratio
      >=300 mg/g was 4.6% versus 0.3%, respectively; eGFR<60 ml/min per 1.73 m2 was 12%
      versus 2.5%, respectively; and eGFR<30 ml/min per 1.73 m2 was 2.4% versus 0.4%,
      respectively (each P<0.001). Adjusting for demographics and several aspects of
      BP, prevalence differences were 14.6% (P<0.001), 10.8% (P<0.001), 4.5% (P<0.001),
      6.5% (P<0.001), and 1.8% (P=0.004), respectively. Approximately 24% (95%
      confidence interval, 19% to 29%) of CKD among all United States adults was
      attributable to diabetes after adjusting for demographics. CONCLUSIONS: Diabetes
      is strongly associated with both albuminuria and reduced GFR independent of
      demographics and hypertension, contributing substantially to the burden of CKD in
      the United States.

PMID- 29054848
TI  - National commitment to shared decision making.

PMID- 29054849
TI  - Minister blames doctors for adverse reactions to mesh implants.

PMID- 29054850
TI  - The paravertebral panto: it's behind you!
AB  - : This case report highlights the utility of paravertebral (PV) imaging in the
      diagnosis of aortic dissection, the evaluation of left ventricular systolic
      function and drawing the distinction between pleural and pericardial effusions.
      In this case, less attenuation of the ultrasound beam, reduced lung viscosity due
      to pleural effusions and less impedance mismatch between media led to images of
      superior quality and high diagnostic value. This supports the use of
      paravertebral imaging as an adjunct to conventional echocardiography windows,
      particularly when conventional transthoracic imaging proves challenging. LEARNING
      POINTS: PV images provide superior resolution when interrogating the descending
      aorta and thus can reveal incidental findings such as aortic dissection.PV
      imaging provides clearer delineation between pericardial and pleural
      effusions.Additional information may be obtained from the PV window in relation
      to left ventricular systolic function particularly in the setting of suboptimal
      transthoracic image quality.

PMID- 29054851
TI  - Changes in the venous pulse waveform in pericardial effusion revealed by Doppler
      echocardiography of the superior vena cava.

PMID- 29054853
TI  - British Thoracic Society guidelines for the management of non-tuberculous
      mycobacterial pulmonary disease (NTM-PD).

PMID- 29054852
TI  - Selective base excision repair of DNA damage by the non-base-flipping DNA
      glycosylase AlkC.
AB  - DNA glycosylases preserve genome integrity and define the specificity of the base
      excision repair pathway for discreet, detrimental modifications, and thus, the
      mechanisms by which glycosylases locate DNA damage are of particular interest.
      Bacterial AlkC and AlkD are specific for cationic alkylated nucleobases and have
      a distinctive HEAT-like repeat (HLR) fold. AlkD uses a unique non-base-flipping
      mechanism that enables excision of bulky lesions more commonly associated with
      nucleotide excision repair. In contrast, AlkC has a much narrower specificity for
      small lesions, principally N3-methyladenine (3mA). Here, we describe how AlkC
      selects for and excises 3mA using a non-base-flipping strategy distinct from that
      of AlkD. A crystal structure resembling a catalytic intermediate complex shows
      how AlkC uses unique HLR and immunoglobulin-like domains to induce a sharp kink
      in the DNA, exposing the damaged nucleobase to active site residues that project
      into the DNA This active site can accommodate and excise N3-methylcytosine (3mC)
      and N1-methyladenine (1mA), which are also repaired by AlkB-catalyzed oxidative
      demethylation, providing a potential alternative mechanism for repair of these
      lesions in bacteria.

PMID- 29054854
TI  - Obesity-Related CKD: When Kidneys Get the Munchies.

PMID- 29054855
TI  - H- ras deletion protects against angiotensin II-induced arterial hypertension and
      cardiac remodeling through protein kinase G-Ibeta pathway activation.
AB  - Ras proteins regulate cell survival, growth, differentiation, blood pressure, and
      fibrosis in some organs. We have demonstrated that H- ras gene deletion produces
      mice hypotension via a soluble guanylate cyclase-protein kinase G (PKG)-dependent
      mechanism. In this study, we analyzed the consequences of H- ras deletion on
      cardiac remodeling induced by continuous angiotensin II (AngII) infusion and the
      molecular mechanisms implied. Left ventricular posterior wall thickness and mass
      and cardiomyocyte cross-sectional area were similar between AngII-treated H-Ras
      knockout (H -ras-/-) and control wild-type (H -ras+/+) mice, as were
      extracellular matrix protein expression. Increased cardiac PKG-Ibeta protein
      expression in H -ras-/- mice suggests the involvement of this protein in heart
      protection. Ex vivo experiments on cardiac explants could support this mechanism,
      as PKG blockade blunted protection against AngII-induced cardiac hypertrophy and
      fibrosis markers in H -ras-/- mice. Genetic modulation studies in cardiomyocytes
      and cardiac and embryonic fibroblasts revealed that the lack of H-Ras down
      regulates the B-RAF/MEK/ERK pathway, which induces the glycogen synthase kinase
      3beta-dependent activation of the transcription factor, cAMP response element
      binding protein, which is responsible for PKG-Ibeta overexpression in H -ras-/-
      mouse embryonic fibroblasts. This study demonstrates that H- ras deletion
      protects against AngII-induced cardiac remodeling, possibly via a mechanism in
      which PKG-Ibeta overexpression could play a partial role, and points to H-Ras
      and/or downstream proteins as potential therapeutic targets in cardiovascular
      disease.-Martin-Sanchez, P., Luengo, A., Griera, M., Orea, M. J., Lopez-Olaneta,
      M., Chiloeches, A., Lara-Pezzi, E., de Frutos, S., Rodriguez-Puyol, M., Calleros,
      L., Rodriguez-Puyol, D. H- ras deletion protects against angiotensin II-induced
      arterial hypertension and cardiac remodeling through protein kinase G-Ibeta
      pathway activation.

PMID- 29054856
TI  - Levels of alpha- and beta-synuclein regulate cellular susceptibility to toxicity
      from alpha-synuclein oligomers.
AB  - alpha-Synuclein (alpha-syn) is associated with a range of diseases, including
      Parkinson disease. In disease, alpha-syn is known to aggregate and has the
      potential to be neurotoxic. The association between copper and alpha-syn results
      in the formation of stellate toxic oligomers that are highly toxic to cultured
      neurons. We further investigated the mechanism of toxicity of alpha-syn
      oligomers. Cells that overexpress alpha-syn showed increased susceptibility to
      the toxicity of the oligomers, while those that overexpressed beta-syn showed
      increased resistance to the toxic oligomers. Elevated alpha-syn expression caused
      an increase in expression of the transcription factor Forkhead box O3a (FoxO3a).
      Inhibition of FoxO3a activity by the overexpression of DNA binding domain of
      FoxO3a resulted in significant protection from alpha-syn oligomer toxicity.
      Increased FoxO3a expression in cells was shown to be caused by increased
      ferrireductase activity and Fe(II) levels. These results suggest that alpha-syn
      increases FoxO3a expression as a result of its intrinsic ferrireductase activity.
      The results also suggest that FoxO3a plays a pivotal role in the toxicity of both
      Fe(II) and toxic alpha-syn species to neuronal cells.-Angelova, D. M., Jones, H.
      B. L., Brown, D. R. Levels of alpha- and beta-synuclein regulate cellular
      susceptibility to toxicity from alpha-synuclein oligomers.

PMID- 29054857
TI  - Diazepam Concurrently Increases the Frequency and Decreases the Amplitude of
      Transient Dopamine Release Events in the Nucleus Accumbens.
AB  - Benzodiazepines are commonly prescribed anxiolytics that pose abuse liability in
      susceptible individuals. Although it is well established that all drugs of abuse
      increase brain dopamine levels, and benzodiazepines are allosteric modulators of
      the GABAA receptor, it remains unclear how they alter dopamine release. Using in
      vivo fast-scan cyclic voltammetry, we measured diazepam-induced changes in the
      frequency and amplitude of transient dopamine release events. We found that
      diazepam concurrently increases the frequency and decreases the amplitude of
      transient dopamine release events in the awake and freely moving rat. The time
      course during which diazepam altered the frequency and amplitude of dopamine
      release events diverged, with the decreased amplitude effect being shorter lived
      than the increase in frequency, but both showing similar rates of onset. We
      conclude that diazepam increases the frequency of accumbal dopamine release
      events by disinhibiting dopamine neurons, but also decreases their amplitude. We
      speculate that the modest abuse liability of benzodiazepines is due to their
      ability to decrease the amplitude of dopamine release events in addition to
      increasing their frequency.

PMID- 29054859
TI  - Quality Protein Maize Based on Reducing Sulfur in Leaf Cells.
AB  - Low levels of the essential amino acids lysine (Lys) and methionine (Met) in a
      maize-based diet are a major cost to feed and food. Lys deficiency is due to the
      abundance of Lys-poor proteins in maize kernels. Although a maize mutant, opaque
      2 (o2), has sufficient levels of Lys, its soft kernel renders it unfit for
      storage and transportation. Breeders overcame this problem by selecting
      quantitative trait loci (QTL) restoring kernel hardness in the presence of o2, a
      variety called Quality Protein Maize (QPM). Although at least one QTL acts by
      enhancing the expression of the gamma-zein proteins, we could surprisingly
      achieve rebalancing of the Lys content and a vitreous kernel phenotype by
      targeting suppression of gamma-zeins without the o2 mutant. Reduced levels of
      gamma-zeins were achieved with RNA interference (RNAi). Another transgenic event,
      PE5 expresses the Escherichia coli enzyme 3'-phosphoadenosine-5'-phosphosulfate
      reductase involved in sulfate assimilation, specifically in leaves. The stacked
      transgenic events produce a vitreous endosperm, which has higher Lys level than
      the classical opaque W64Ao2 variant. Moreover, due to the increased sulfate
      reduction in the leaf, Met level is elevated in the seed. Such a combination of
      transgenes produces hybrid seeds superior to classical QPMs that would neither
      require a costly feed mix nor synthetic Met supplementation, potentially creating
      a novel and cost-effective means for improving maize nutritional quality.

PMID- 29054858
TI  - MicroRNA-Directed Cancer Therapies: Implications in Melanoma Intervention.
AB  - Acquired tumor resistance to cancer therapies poses major challenges in the
      treatment of cancers including melanoma. Among several signaling pathways or
      factors that affect neocarcinogenesis, cancer progression, and therapies, altered
      microRNAs (miRNAs) expression has been identified as a crucial player in
      modulating the key pathways governing these events. While studies in the miRNA
      field have grown exponentially in the last decade, much remains to be discovered,
      particularly with respect to their roles in cancer therapies. Since immune and
      nonimmune signaling cascades prevail in cancers, identification and evaluation of
      miRNAs, their molecular mechanisms and cellular targets involved in the
      underlying development of cancers, and acquired therapeutic resistance would help
      in devising new strategies for the prognosis, treatment, and an early detection
      of recurrence. Importantly, in-depth validation of miRNA-targeted molecular
      events could lead to the development of accurate progression-risk biomarkers,
      improved effectiveness, and improved patient responses to standard therapies. The
      current review focuses on the roles of miRNAs with recent updates on regulated
      cell cycle and proliferation, immune responses, oncogenic/epigenetic signaling
      pathways, invasion, metastasis, and apoptosis, with broader attention paid to
      melanomagenesis and melanoma therapies.

PMID- 29054860
TI  - Post-prandial hyperlipidaemia results in systemic nitrosative stress and impaired
      cerebrovascular function in the aged.
AB  - Post-prandial hyperlipidaemia (PPH) acutely impairs systemic vascular endothelial
      function, potentially attributable to a free radical-mediated reduction in
      vascular nitric oxide (NO) bioavailability (oxidative-nitrosative stress).
      However, it remains to be determined whether this extends to the
      cerebrovasculature. To examine this, 38 (19 young (<=35 years) and 19 aged (>=60
      years)) healthy males were recruited. Cerebrovascular function (middle cerebral
      artery velocity, MCAv) and cerebrovascular reactivity to hypercapnea
      (CVRCO2Hyper) and hypocapnea (CVRCO2Hypo) were determined via trans-cranial
      Doppler ultrasound and capnography. Venous blood samples were obtained for the
      assessment of triglycerides (photometry), glucose (photometry), insulin
      (radioimmunoassay), ascorbate free radical (A*-, electron paramagnetic resonance
      spectroscopy) and nitrite (NO2-, ozone-based chemiluminescence) in the fasted
      state prior to and 4 h following consumption of a standardized high-fat meal
      (1362 kcal; 130 g of fat). Circulating triglycerides, glucose and insulin
      increased in both groups following the high-fat meal (P<0.05), with triglycerides
      increasing by 1.37 +/- 1.09 mmol/l in the young and 1.54 +/- 1.00 mmol/l in the
      aged (P<0.05). This resulted in an increased systemic formation of free radicals
      in the young (P<0.05) but not the aged (P>0.05) and corresponding reduction in
      NO2- in both groups (P<0.05). While the meal had no effect on MCAv in either age
      group, CVRCO2Hyper was selectively impaired in the aged (P<0.05). These findings
      indicate that PPH causes acute cerebrovascular dysfunction in the aged subsequent
      to systemic nitrosative stress.

PMID- 29054861
TI  - Regulation of human feto-placental endothelial barrier integrity by vascular
      endothelial growth factors: competitive interplay between VEGF-A165a, VEGF-A165b,
      PIGF and VE-cadherin.
AB  - The human placenta nourishes and protects the developing foetus whilst
      influencing maternal physiology for fetal advantage. It expresses several members
      of the vascular endothelial growth factor (VEGF) family including the pro
      angiogenic/pro-permeability VEGF-A165a isoform, the anti-angiogenic VEGF-A165b,
      placental growth factor (PIGF) and their receptors, VEGFR1 and VEGFR2.
      Alterations in the ratio of these factors during gestation and in complicated
      pregnancies have been reported; however, the impact of this on feto-placental
      endothelial barrier integrity is unknown. The present study investigated the
      interplay of these factors on junctional occupancy of VE-cadherin and
      macromolecular leakage in human endothelial monolayers and the perfused placental
      microvascular bed. Whilst VEGF-A165a (50 ng/ml) increased endothelial monolayer
      albumin permeability (P<0.0001), equimolar concentrations of VEGF-A165b (P>0.05)
      or PlGF (P>0.05) did not. Moreover, VEGF-A165b (100 ng/ml; P<0.001) but not PlGF
      (100 ng/ml; P>0.05) inhibited VEGF-A165a-induced permeability when added singly.
      PlGF abolished the VEGF-A165b-induced reduction in VEGF-A165a-mediated
      permeability (P>0.05); PlGF was found to compete with VEGF-A165b for binding to
      Flt-1 at equimolar affinity. Junctional occupancy of VE-cadherin matched
      alterations in permeability. In the perfused microvascular bed, VEGF-A165b did
      not induce microvascular leakage but inhibited and reversed VEGF-A165a-induced
      loss of junctional VE-cadherin and tracer leakage. These results indicate that
      the anti-angiogenic VEGF-A165b isoform does not increase permeability in human
      placental microvessels or HUVEC primary cells and can interrupt VEGF-A165a
      induced permeability. Moreover, the interplay of these isoforms with PIGF (and s
      flt1) suggests that the ratio of these three factors may be important in
      determining the placental and endothelial barrier in normal and complicated
      pregnancies.

PMID- 29054863
TI  - Private sector needs extensive reform to protect patients, says think tank.

PMID- 29054862
TI  - Current evidence-based recommendations on investigating children with global
      developmental delay.
AB  - INTRODUCTION: Global developmental delay (GDD) affects 1%-3% of the population of
      children under 5 years of age, making it one of the most common conditions
      presenting in paediatric clinics; causes are exogenous, genetic (non-metabolic)
      or genetic (metabolic). Recent advances in biotechnology and genetic testing mean
      that the investigations available to perform for children under 5 years are
      increasing and are more sensitive than previously. This change in availability
      and type of testing necessitates an update in the recommendations for
      investigating GDD. METHODS: We conducted a review of the literature from 2006 to
      2016 to identify articles with evidence relating to the investigation of
      developmental delay in children under the age of 5 years. We collated the
      evidence into first-line and second-line investigations and, where available, on
      their yield and cost implications. RESULTS: We have provided up-to-date guidance
      for first-line and second-line investigations for children with GDD under the age
      of 5 years. Recent evidence demonstrates that genetic testing for all children
      with unexplained GDD should be first line, if an exogenous cause is not already
      established. Our review of the literature demonstrates that all patients,
      irrespective of severity of GDD, should have investigations for treatable
      conditions. Evidence demonstrates that the yield for treatable conditions is
      higher than previously thought and that investigations for these metabolic
      conditions should be considered as first line. Additional second-line
      investigations can be led by history, examination and developmental trajectories.
      DISCUSSION: We may need to update present recommendations in the UK for
      investigation of developmental delay. This would include microarray testing as
      first line and a more thorough approach to investigations for metabolic disorders
      that can be treated. Clinical assessment remains vital for guiding
      investigations.

PMID- 29054865
TI  - A symporter's secrets shown.
AB  - New JGP study explores the thermodynamic cycle and cation preference of the sugar
      symporter MelB.

PMID- 29054864
TI  - Heterogeneous Patterns of Genetic Diversity and Differentiation in European and
      Siberian Chiffchaff (Phylloscopus collybita abietinus/P. tristis).
AB  - Identification of candidate genes for trait variation in diverging lineages and
      characterization of mechanistic underpinnings of genome differentiation are key
      steps toward understanding the processes underlying the formation of new species.
      Hybrid zones provide a valuable resource for such investigations, since they
      allow us to study how genomes evolve as species exchange genetic material and to
      associate particular genetic regions with phenotypic traits of interest. Here, we
      use whole-genome resequencing of both allopatric and hybridizing populations of
      the European (Phylloscopus collybita abietinus) and the Siberian chiffchaff (P.
      tristis)-two recently diverged species which differ in morphology, plumage, song,
      habitat, and migration-to quantify the regional variation in genome-wide genetic
      diversity and differentiation, and to identify candidate regions for trait
      variation. We find that the levels of diversity, differentiation, and divergence
      are highly heterogeneous, with significantly reduced global differentiation, and
      more pronounced differentiation peaks in sympatry than in allopatry. This pattern
      is consistent with regional differences in effective population size and
      recurrent background selection or selective sweeps reducing the genetic diversity
      in specific regions prior to lineage divergence, but the data also suggest that
      postdivergence selection has resulted in increased differentiation and fixed
      differences in specific regions. We find that hybridization and backcrossing is
      common in sympatry, and that phenotype is a poor predictor of the genomic
      composition of sympatric birds. The combination of a differentiation scan
      approach with identification of fixed differences pinpoint a handful of candidate
      regions that might be important for trait variation between the two species.

PMID- 29054866
TI  - Subtle mutation, far-reaching effects.

PMID- 29054867
TI  - Thermodynamic cooperativity of cosubstrate binding and cation selectivity of
      Salmonella typhimurium MelB.
AB  - The Na+-coupled melibiose symporter MelB, which can also be coupled to H+ or Li+
      transport, is a prototype for the glycoside-pentoside-hexuronide:cation symporter
      family. Although the 3-D x-ray crystal structure of Salmonella typhimurium MelB
      (MelBSt) has been determined, the symport mechanisms for the obligatory coupled
      transport are not well understood. Here, we apply isothermal titration
      calorimetry to determine the energetics of Na+ and melibiose binding to MelBSt,
      as well as protonation of this transporter. Studies of the thermodynamic cycle
      for the formation of the Na+-MelBSt-melibiose ternary complex at pH 7.45 reveal
      that the binding of Na+ and melibiose is cooperative. The binding affinity for
      one substrate (Na+ or melibiose) is increased by the presence of the other by
      about eightfold. The coupling free energies (DeltaDeltaG) of either substrate
      binding are ~5 kJ/mol, and binding of both substrates releases a free energy of
      ~35 kJ/mol. Measurements of the Na+-binding enthalpy at three different pH
      values, including the pKa value of MelB, indicate that the binding of one Na+
      displaces one H+ per MelBSt molecule. In addition, the absolute dissociation
      constants for Na+ and H+, determined by competitive binding, show that MelBSt is
      selective for H+ over Na+ by ~1,000-fold at a pKa of 6.25. Thus, the Na+ coupling
      in MelBSt is based not on ion selectivity but on ion concentrations and
      competitive binding because of a much higher Na+ concentration under
      physiological conditions. Such a selectivity feature seems to be common for
      membrane transport proteins that can bind both H+ and Na+ at a common site.

PMID- 29054868
TI  - Conditional Function of Autoaggregative Protein Cah and Common cah Mutations in
      Shiga Toxin-Producing Escherichia coli.
AB  - Cah is a calcium-binding autotransporter protein involved in autoaggregation and
      biofilm formation. Although cah is widespread in Shiga toxin-producing
      Escherichia coli (STEC), we detected mutations in cah at a frequency of 31.3% in
      this pathogen. In STEC O157:H7 supershedder strain SS17, a large deletion results
      in a smaller coding sequence, encoding a protein lacking the C-terminal 71 amino
      acids compared with Cah in STEC O157:H7 strain EDL933. We examined the function
      of Cah in biofilm formation and host colonization to better understand the
      selective pressures for cah mutations. EDL933-Cah played a conditional role in
      biofilm formation in vitro: it enhanced E. coli DH5alpha biofilm formation on
      glass surfaces under agitated culture conditions that prevented autoaggregation
      but inhibited biofilm formation under hydrostatic conditions that facilitated
      autoaggregation. This function appeared to be strain dependent since Cah-mediated
      biofilm formation was diminished when an EDL933 cah gene was expressed in SS17.
      Deletion of cah in EDL933 enhanced bacterial attachment to spinach leaves and
      altered the adherence pattern of EDL933 to bovine recto-anal junction squamous
      epithelial (RSE) cells. In contrast, in trans expression of EDL933 cah in SS17
      increased its attachment to leaf surfaces, and in DH5alpha, it enhanced its
      adherence to RSE cells. Hence, the ecological function of Cah appears to be
      modulated by environmental conditions and other bacterial strain-specific
      properties. Considering the prevalence of cah in STEC and its role in attachment
      and biofilm formation, cah mutations might be selected in ecological niches in
      which inactivation of Cah would result in an increased fitness in STEC during
      colonization of plants or animal hosts.IMPORTANCE Shiga toxin-producing
      Escherichia coli (STEC) harbors genes encoding diverse adhesins, and many of
      these are known to play an important role in bacterial attachment and host
      colonization. We demonstrated here that the autotransporter protein Cah confers
      on E. coli DH5alpha cells a strong autoaggregative phenotype that is inversely
      correlated with its ability to form biofilms and plays a strain-specific role in
      plant and animal colonization by STEC. Although cah is widespread in the STEC
      population, we detected a mutation rate of 31.3% in cah, which is similar to that
      reported for rpoS and fimH The formation of cell aggregates due to increased
      bacterium-to-bacterium interactions may be disadvantageous to bacterial
      populations under conditions that favor a planktonic state in STEC. Therefore, a
      loss-of-function mutation in cah is likely a selective trait in STEC when
      autoaggregative properties become detrimental to bacterial cells and may
      contribute to the adaptability of STEC to fluctuating environments.

PMID- 29054869
TI  - Estimating Population Turnover Rates by Relative Quantification Methods Reveals
      Microbial Dynamics in Marine Sediment.
AB  - The difficulty involved in quantifying biogeochemically significant microbes in
      marine sediments limits our ability to assess interspecific interactions,
      population turnover times, and niches of uncultured taxa. We incubated surface
      sediments from Cape Lookout Bight, North Carolina, USA, anoxically at 21 degrees
      C for 122 days. Sulfate decreased until day 68, after which methane increased,
      with hydrogen concentrations consistent with the predicted values of an electron
      donor exerting thermodynamic control. We measured turnover times using two
      relative quantification methods, quantitative PCR (qPCR) and the product of 16S
      gene read abundance and total cell abundance (FRAxC, which stands for "fraction
      of read abundance times cells"), to estimate the population turnover rates of
      uncultured clades. Most 16S rRNA reads were from deeply branching uncultured
      groups, and ~98% of 16S rRNA genes did not abruptly shift in relative abundance
      when sulfate reduction gave way to methanogenesis. Uncultured Methanomicrobiales
      and Methanosarcinales increased at the onset of methanogenesis with population
      turnover times estimated from qPCR at 9.7 +/- 3.9 and 12.6 +/- 4.1 days,
      respectively. These were consistent with FRAxC turnover times of 9.4 +/- 5.8 and
      9.2 +/- 3.5 days, respectively. Uncultured Syntrophaceae, which are possibly
      fermentative syntrophs of methanogens, and uncultured Kazan-3A-21 archaea also
      increased at the onset of methanogenesis, with FRAxC turnover times of 14.7 +/-
      6.9 and 10.6 +/- 3.6 days. Kazan-3A-21 may therefore either perform
      methanogenesis or form a fermentative syntrophy with methanogens. Three genera of
      sulfate-reducing bacteria, Desulfovibrio, Desulfobacter, and Desulfobacterium,
      increased in the first 19 days before declining rapidly during sulfate reduction.
      We conclude that population turnover times on the order of days can be measured
      robustly in organic-rich marine sediment, and the transition from sulfate
      reducing to methanogenic conditions stimulates growth only in a few clades
      directly involved in methanogenesis, rather than in the whole microbial
      community.IMPORTANCE Many microbes cannot be isolated in pure culture to
      determine their preferential growth conditions and predict their response to
      changing environmental conditions. We created a microcosm of marine sediments
      that allowed us to simulate a diagenetic profile using a temporal analog for
      depth. This allowed for the observation of the microbial community population
      dynamics caused by the natural shift from sulfate reduction to methanogenesis.
      Our research provides evidence for the population dynamics of uncultured microbes
      as well as the application of a novel method of turnover rate analysis for
      individual taxa within a mixed incubation, FRAxC, which stands for "fraction of
      read abundance times cells," which was verified by quantitative PCR. This allows
      for the calculation of population turnover times for microbes in a natural
      setting and the identification of uncultured clades involved in geochemical
      processes.

PMID- 29054870
TI  - Synthesis of Heterologous Mevalonic Acid Pathway Enzymes in Clostridium
      ljungdahlii for the Conversion of Fructose and of Syngas to Mevalonate and
      Isoprene.
AB  - There is a growing interest in the use of microbial fermentation for the
      generation of high-demand, high-purity chemicals using cheap feedstocks in an
      environmentally friendly manner. One example explored here is the production of
      isoprene (C5H8), a hemiterpene, which is primarily polymerized to polyisoprene in
      synthetic rubber in tires but which can also be converted to C10 and C15
      biofuels. The strictly anaerobic, acetogenic bacterium Clostridium ljungdahlii,
      used in all of the work described here, is capable of glycolysis using the Embden
      Meyerhof-Parnas pathway and of carbon fixation using the Wood-Ljungdahl pathway.
      Clostridium-Escherichia coli shuttle plasmids, each bearing either 2 or 3
      different heterologous genes of the eukaryotic mevalonic acid (MVA) pathway or
      eukaryotic isopentenyl pyrophosphate isomerase (Idi) and isoprene synthase
      (IspS), were constructed and electroporated into C. ljungdahlii These plasmids,
      one or two of which were introduced into the host cells, enabled the synthesis of
      mevalonate and of isoprene from fructose and from syngas (H2, CO2, and CO) and
      the conversion of mevalonate to isoprene. All of the heterologous enzymes of the
      MVA pathway, as well as Idi and IspS, were shown to be synthesized at high levels
      in C. ljungdahlii, as demonstrated by Western blotting, and were enzymatically
      active, as demonstrated by in vivo product synthesis. The quantities of
      mevalonate and isoprene produced here are far below what would be required of a
      commercial production strain. However, proposals are made that could enable a
      substantial increase in the mass yield of product formation.IMPORTANCE This study
      demonstrates the ability to synthesize a heterologous metabolic pathway in C.
      ljungdahlii, an organism capable of metabolizing either simple sugars or syngas
      or both together (mixotrophy). Syngas, an inexpensive source of carbon and
      reducing equivalents, is produced as a major component of some industrial waste
      gas, and it can be generated by gasification of cellulosic biowaste and of
      municipal solid waste. Its conversion to useful products therefore offers
      potential cost and environmental benefits. The ability of C. ljungdahlii to grow
      mixotrophically also enables the recapture, should there be sufficient reducing
      equivalents available, of the CO2 released upon glycolysis, potentially
      increasing the mass yield of product formation. Isoprene is the simplest of the
      terpenoids, and so the demonstration of its production is a first step toward the
      synthesis of higher-value products of the terpenoid pathway.

PMID- 29054871
TI  - Engineering the Enantioselectivity and Thermostability of a (+)-gamma-Lactamase
      from Microbacterium hydrocarbonoxydans for Kinetic Resolution of Vince Lactam (2
      Azabicyclo[2.2.1]hept-5-en-3-one).
AB  - To produce promising biocatalysts, natural enzymes often need to be engineered to
      increase their catalytic performance. In this study, the enantioselectivity and
      thermostability of a (+)-gamma-lactamase from Microbacterium hydrocarbonoxydans
      as the catalyst in the kinetic resolution of Vince lactam (2
      azabicyclo[2.2.1]hept-5-en-3-one) were improved. Enantiomerically pure (-)-Vince
      lactam is the key synthon in the synthesis of antiviral drugs, such as carbovir
      and abacavir, which are used to fight against HIV and hepatitis B virus. The work
      was initialized by using the combinatorial active-site saturation test strategy
      to engineer the enantioselectivity of the enzyme. The approach resulted in two
      mutants, Val54Ser and Val54Leu, which catalyzed the hydrolysis of Vince lactam to
      give (-)-Vince lactam, with 99.2% (enantiomeric ratio [E] > 200) enantiomeric
      excess (ee) and 99.5% ee (E > 200), respectively. To improve the thermostability
      of the enzyme, 11 residues with high temperature factors (B-factors) calculated
      by B-FITTER or high root mean square fluctuation (RMSF) values from the molecular
      dynamics simulation were selected. Six mutants with increased thermostability
      were obtained. Finally, the mutants generated with improved enantioselectivity
      and mutants evolved for enhanced thermostability were combined. Several variants
      showing (+)-selectivity (E value > 200) and improved thermostability were
      observed. These engineered enzymes are good candidates to serve as
      enantioselective catalysts for the preparation of enantiomerically pure Vince
      lactam.IMPORTANCE Enzymatic kinetic resolution of the racemic Vince lactam using
      (+)-gamma-lactamase is the most often utilized means of resolving the enantiomers
      for the preparation of carbocyclic nucleoside compounds. The efficiency of the
      native enzymes could be improved by using protein engineering methods, such as
      directed evolution and rational design. In our study, two properties
      (enantioselectivity and thermostability) of a gamma-lactamase identified from
      Microbacterium hydrocarbonoxydans were tackled using a semirational design. The
      protein engineering was initialized by combinatorial active-site saturation test
      to improve the enantioselectivity. At the same time, two strategies were applied
      to identify mutation candidates to enhance the thermostability based on
      calculations from both a static (B-FITTER based on the crystal structure) and a
      dynamic (root mean square fluctuation [RMSF] values based on molecular dynamics
      simulations) way. After combining the mutants, we successfully obtained the final
      mutants showing better properties in both properties. The engineered (+)
      lactamase could be a candidate for the preparation of (-)-Vince lactam.

PMID- 29054872
TI  - Transcriptional Activities of the Microbial Consortium Living with the Marine
      Nitrogen-Fixing Cyanobacterium Trichodesmium Reveal Potential Roles in Community
      Level Nitrogen Cycling.
AB  - Trichodesmium is a globally distributed cyanobacterium whose nitrogen-fixing
      capability fuels primary production in warm oligotrophic oceans. Like many
      photoautotrophs, Trichodesmium serves as a host to various other microorganisms,
      yet little is known about how this associated community modulates fluxes of
      environmentally relevant chemical species into and out of the supraorganismal
      structure. Here, we utilized metatranscriptomics to examine gene expression
      activities of microbial communities associated with Trichodesmium erythraeum
      (strain IMS101) using laboratory-maintained enrichment cultures that have
      previously been shown to harbor microbial communities similar to those of natural
      populations. In enrichments maintained under two distinct CO2 concentrations for
      ~8 years, the community transcriptional profiles were found to be specific to the
      treatment, demonstrating a restructuring of overall gene expression had occurred.
      Some of this restructuring involved significant increases in community
      respiration-related transcripts under elevated CO2, potentially facilitating the
      corresponding measured increases in host nitrogen fixation rates. Particularly of
      note, in both treatments, community transcripts involved in the reduction of
      nitrate, nitrite, and nitrous oxide were detected, suggesting the associated
      organisms may play a role in colony-level nitrogen cycling. Lastly, a taxon
      specific analysis revealed distinct ecological niches of consistently cooccurring
      major taxa that may enable, or even encourage, the stable cohabitation of a
      diverse community within Trichodesmium consortia.IMPORTANCETrichodesmium is a
      genus of globally distributed, nitrogen-fixing marine cyanobacteria. As a source
      of new nitrogen in otherwise nitrogen-deficient systems, these organisms help
      fuel carbon fixation carried out by other more abundant photoautotrophs and
      thereby have significant roles in global nitrogen and carbon cycling. Members of
      the Trichodesmium genus tend to form large macroscopic colonies that appear to
      perpetually host an association of diverse interacting microbes distinct from the
      surrounding seawater, potentially making the entire assemblage a unique miniature
      ecosystem. Since its first successful cultivation in the early 1990s, there have
      been questions about the potential interdependencies between Trichodesmium and
      its associated microbial community and whether the host's seemingly enigmatic
      nitrogen fixation schema somehow involved or benefited from its epibionts. Here,
      we revisit these old questions with new technology and investigate gene
      expression activities of microbial communities living in association with
      Trichodesmium.

PMID- 29054874
TI  - Extracellular Polymeric Matrix Production and Relaxation under Fluid Shear and
      Mechanical Pressure in Staphylococcus aureus Biofilms.
AB  - The viscoelasticity of a biofilm's EPS (extracellular-polymeric-substance) matrix
      conveys protection against mechanical challenges, but adaptive responses of
      biofilm inhabitants to produce EPS are not well known. Here, we compare the
      response of a biofilm of an EPS producing (ATCC 12600) and non-EPS producing
      (5298) Staphylococcus aureus strain to fluid shear and mechanical challenge.
      Confocal-Laser-Scanning-Microscopy confirmed absence of calcofluorwhite-stainable
      EPS in biofilms of S. aureus 5298. ATR-FTIR spectroscopy combined with tribometry
      indicated that the polysaccharide production per bacterium in the initial
      adhering layer was higher during growth at high shear than at low shear and this
      increased EPS production extended to entire biofilms, as indicated by
      tribometrically measured coefficients of friction (CoF). CoFs of biofilms grown
      under high fluid shear were higher than when grown under low shear, likely due to
      wash-off of polysaccharides. Measurement of a biofilm's CoF implies application
      of mechanical pressure that yielded an immediate increase in polysaccharide band
      area of S. aureus ATCC 12600 biofilms due to their compression that decreased
      after relieving pressure to the level observed prior to mechanical pressure. For
      biofilms grown under high shear, this coincided with a higher %whiteness in
      Optical-Coherence-Tomography-images indicative of water outflow, returning back
      into the biofilm during stress relaxation. Biofilms grown under low shear
      however, were stimulated during tribometry to produce EPS, also after stress
      relieve. Knowledge of factors that govern EPS production and water flow in
      biofilms will allow better control of biofilms under mechanical challenge and
      understanding of the barrier properties of biofilms toward antimicrobial
      penetration.IMPORTANCE Adaptive responses of biofilm inhabitants in nature to
      environmental challenges such as fluid shear and mechanical pressure, often
      involve EPS production with the aim of protecting biofilm inhabitants. EPS can
      assist biofilm bacteria to remain attached or impede antimicrobial penetration.
      The tribochemist is a recently introduced instrument, allowing to study initially
      adhering bacteria to a Germanium crystal using ATR-FTIR spectroscopy, while
      simultaneously allowing measurement of the coefficient of friction of a biofilm,
      serving as an indicator of the EPS content of a biofilm. EPS production can be
      stimulated by both fluid shear during growth and mechanical pressure, while
      increased EPS production can continue after pressure relaxation of the biofilm.
      Since EPS is pivotal in the protection of biofilm inhabitants against mechanical
      and chemical challenges, knowledge the factors that make biofilm inhabitants
      decide to produce EPS as provided in this study, are important for the
      development of biofilm control measures.

PMID- 29054873
TI  - The Enigmatic Genome of an Obligate Ancient Spiroplasma Symbiont in a Hadal
      Holothurian.
AB  - Protective symbiosis has been reported in many organisms, but the molecular
      mechanisms of the mutualistic interactions between the symbionts and their hosts
      are unclear. Here, we sequenced the 424-kbp genome of "Candidatus Spiroplasma
      holothuricola," which dominated the hindgut microbiome of a sea cucumber, a major
      scavenger captured in the Mariana Trench (6,140 m depth). Phylogenetic
      relationships indicated that the dominant bacterium in the hindgut was derived
      from a basal group of Spiroplasma species. In this organism, the genes
      responsible for the biosynthesis of amino acids, glycolysis, and sugar
      transporters were lost, strongly suggesting endosymbiosis. The highly decayed
      genome consists of two chromosomes and harbors genes coding for proteolysis,
      microbial toxin, restriction-methylation systems, and clustered regularly
      interspaced short palindromic repeats (CRISPRs), composed of three cas genes and
      76 CRISPR spacers. The holothurian host is probably protected against invading
      viruses from sediments by the CRISPRs/Cas and restriction systems of the
      endosymbiotic spiroplasma. The protective endosymbiosis indicates the important
      ecological role of the ancient Spiroplasma symbiont in the maintenance of hadal
      ecosystems.IMPORTANCE Sea cucumbers are major inhabitants in hadal trenches. They
      collect microbes in surface sediment and remain tolerant against potential
      pathogenic bacteria and viruses. This study presents the genome of endosymbiotic
      spiroplasmas in the gut of a sea cucumber captured in the Mariana Trench. The
      extreme reduction of the genome and loss of essential metabolic pathways strongly
      support its endosymbiotic lifestyle. Moreover, a considerable part of the genome
      was occupied by a CRISPR/Cas system to provide immunity against viruses and
      antimicrobial toxin-encoding genes for the degradation of microbes. This novel
      species of Spiroplasma is probably an important protective symbiont for the sea
      cucumbers in the hadal zone.

PMID- 29054875
TI  - A Novel Steroid-Coenzyme A Ligase from Novosphingobium sp. Strain Chol11 Is
      Essential for an Alternative Degradation Pathway for Bile Salts.
AB  - Bile salts such as cholate are steroid compounds with a C5 carboxylic side chain
      and occur ubiquitously in vertebrates. Upon their excretion into soils and
      waters, bile salts can serve as growth substrates for diverse bacteria.
      Novosphingobium sp. strain Chol11 degrades 7-hydroxy bile salts via 3-keto-7
      deoxy-Delta4,6 metabolites by the dehydration of the 7-hydroxyl group catalyzed
      by the 7alpha-hydroxysteroid dehydratase Hsh2. This reaction has not been
      observed in the well-studied 9-10-seco degradation pathway used by other steroid
      degrading bacteria indicating that strain Chol11 uses an alternative pathway. A
      reciprocal BLASTp analysis showed that known side chain degradation genes from
      other cholate-degrading bacteria (Pseudomonas stutzeri Chol1, Comamonas
      testosteroni CNB-2, and Rhodococcus jostii RHA1) were not found in the genome of
      strain Chol11. The characterization of a transposon mutant of strain Chol11
      showing altered growth with cholate identified a novel steroid-24-oyl-coenzyme A
      ligase named SclA. The unmarked deletion of sclA resulted in a strong growth rate
      decrease with cholate, while growth with steroids with C3 side chains or without
      side chains was not affected. Intermediates with a 7-deoxy-3-keto-Delta4,6
      structure, such as 3,12-dioxo-4,6-choldienoic acid (DOCDA), were shown to be
      likely physiological substrates of SclA. Furthermore, a novel coenzyme A (CoA)
      dependent DOCDA degradation metabolite with an additional double bond in the side
      chain was identified. These results support the hypothesis that Novosphingobium
      sp. strain Chol11 harbors an alternative pathway for cholate degradation, in
      which side chain degradation is initiated by the CoA ligase SclA and proceeds via
      reaction steps catalyzed by so-far-unknown enzymes different from those of other
      steroid-degrading bacteria.IMPORTANCE This study provides further evidence of the
      diversity of metabolic pathways for the degradation of steroid compounds in
      environmental bacteria. The knowledge about these pathways contributes to the
      understanding of the CO2-releasing part of the global C cycle. Furthermore, it is
      useful for investigating the fate of pharmaceutical steroids in the environment,
      some of which may act as endocrine disruptors.

PMID- 29054876
TI  - A Canonical Biotin Synthesis Enzyme, 8-Amino-7-Oxononanoate Synthase (BioF),
      Utilizes Different Acyl Chain Donors in Bacillus subtilis and Escherichia coli.
AB  - BioF (8-amino-7-oxononanoate synthase) is a strictly conserved enzyme that
      catalyzes the first step in assembly of the fused heterocyclic rings of biotin.
      The BioF acyl chain donor has long been thought to be pimeloyl-CoA. Indeed, in
      vitro the Escherichia coli and Bacillus sphaericus enzymes have been shown to
      condense pimeloyl-CoA with l-alanine in a pyridoxal 5'-phosphate-dependent
      reaction with concomitant CoA release and decarboxylation of l-alanine. However,
      recent in vivo studies of E. coli and Bacillus subtilis suggested that the BioF
      proteins of the two bacteria could have different specificities for pimelate
      thioesters in that E. coli BioF may utilize either pimeloyl coenzyme A (CoA) or
      the pimelate thioester of the acyl carrier protein (ACP) of fatty acid synthesis.
      In contrast, B. subtilis BioF seemed likely to be specific for pimeloyl-CoA and
      unable to utilize pimeloyl-ACP. We now report genetic and in vitro data
      demonstrating that B. subtilis BioF specifically utilizes pimeloyl-CoA.IMPORTANCE
      Biotin is an essential vitamin required by mammals and birds because, unlike
      bacteria, plants, and some fungi, these organisms cannot make biotin. Currently,
      the biotin included in vitamin tablets and animal feeds is made by chemical
      synthesis. This is partly because the biosynthetic pathways in bacteria are
      incompletely understood. This paper defines an enzyme of the Bacillus subtilis
      pathway and shows that it differs from that of Escherichia coli in the ability to
      utilize specific precursors. These bacteria have been used in biotin production
      and these data may aid in making biotin produced by biotechnology commercially
      competitive with that produced by chemical synthesis.

PMID- 29054877
TI  - Ontogeny of Circadian Rhythms and Synchrony in the Suprachiasmatic Nucleus.
AB  - In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus coordinates
      daily rhythms including sleep-wake, hormone release, and gene expression. The
      cells of the SCN must synchronize to each other to drive these circadian rhythms
      in the rest of the body. The ontogeny of circadian cycling and intercellular
      coupling in the SCN remains poorly understood. Recent in vitro studies have
      recorded circadian rhythms from the whole embryonic SCN. Here, we tracked the
      onset and precision of rhythms in PERIOD2 (PER2), a clock protein, within the SCN
      isolated from embryonic and postnatal mice of undetermined sex. We found that a
      few SCN cells developed circadian periodicity in PER2 by 14.5 d after mating
      (E14.5) with no evidence for daily cycling on E13.5. On E15.5, the fraction of
      competent oscillators increased dramatically corresponding with stabilization of
      their circadian periods. The cells of the SCN harvested at E15.5 expressed
      sustained, synchronous daily rhythms. By postnatal day 2 (P2), SCN oscillators
      displayed the daily, dorsal-ventral phase wave in clock gene expression typical
      of the adult SCN. Strikingly, vasoactive intestinal polypeptide (VIP), a
      neuropeptide critical for synchrony in the adult SCN, and its receptor, VPAC2R,
      reached detectable levels after birth and after the onset of circadian synchrony.
      Antagonists of GABA or VIP signaling or action potentials did not disrupt
      circadian synchrony in the E15.5 SCN. We conclude that endogenous daily rhythms
      in the fetal SCN begin with few noisy oscillators on E14.5, followed by
      widespread oscillations that rapidly synchronize on E15.5 by an unknown
      mechanism.SIGNIFICANCE STATEMENT We recorded the onset of PER2 circadian
      oscillations during embryonic development in the mouse SCN. When isolated at
      E13.5, the anlagen of the SCN expresses high, arrhythmic PER2. In contrast, a few
      cells show noisy circadian rhythms in the isolated E14.5 SCN and most show
      reliable, self-sustained, synchronized rhythms in the E15.5 SCN. Strikingly, this
      synchrony at E15.5 appears before expression of VIP or its receptor and persists
      in the presence of blockers of VIP, GABA or neuronal firing. Finally, the dorsal
      ventral phase wave of PER2 typical of the adult SCN appears ~P2, indicating that
      multiple signals may mediate circadian synchrony during the ontogeny of the SCN.

PMID- 29054878
TI  - Pathological Tau Strains from Human Brains Recapitulate the Diversity of
      Tauopathies in Nontransgenic Mouse Brain.
AB  - Pathological tau aggregates occur in Alzheimer's disease (AD) and other
      neurodegenerative tauopathies. It is not clearly understood why tauopathies vary
      greatly in the neuroanatomical and histopathological patterns of tau aggregation,
      which contribute to clinical heterogeneity in these disorders. Recent studies
      have shown that tau aggregates may form distinct structural conformations, known
      as tau strains. Here, we developed a novel model to test the hypothesis that cell
      to-cell transmission of different tau strains occurs in nontransgenic (non-Tg)
      mice, and to investigate whether there are strain-specific differences in the
      pattern of tau transmission. By injecting pathological tau extracted from
      postmortem brains of AD (AD-tau), progressive supranuclear palsy (PSP-tau), and
      corticobasal degeneration (CBD-tau) patients into different brain regions of
      female non-Tg mice, we demonstrated the induction and propagation of endogenous
      mouse tau aggregates. Specifically, we identified differences in tau strain
      potency between AD-tau, CBD-tau, and PSP-tau in non-Tg mice. Moreover,
      differences in cell-type specificity of tau aggregate transmission were observed
      between tau strains such that only PSP-tau and CBD-tau strains induce astroglial
      and oligodendroglial tau inclusions, recapitulating the diversity of
      neuropathology in human tauopathies. Furthermore, we demonstrated that the
      neuronal connectome, but not the tau strain, determines which brain regions
      develop tau pathology. Finally, CBD-tau- and PSP-tau-injected mice showed
      spatiotemporal transmission of glial tau pathology, suggesting glial tau
      transmission contributes to the progression of tauopathies. Together, our data
      suggest that different tau strains determine seeding potency and cell-type
      specificity of tau aggregation that underlie the diversity of human
      tauopathies.SIGNIFICANCE STATEMENT Tauopathies show great clinical and
      neuropathological heterogeneity, despite the fact that tau aggregates in each
      disease. This heterogeneity could be due to tau aggregates forming distinct
      structural conformations, or strains. We now report the development of a sporadic
      tauopathy model to study human tau strains by intracerebrally injecting
      nontransgenic mice with pathological tau enriched from human tauopathy brains. We
      show human tau strains seed different types and cellular distributions of tau
      neuropathology in our model that recapitulate the heterogeneity seen in these
      human diseases.

PMID- 29054879
TI  - Domain Specificity of Oculomotor Learning after Changes in Sensory Processing.
AB  - Humans visually process the world with varying spatial resolution and can program
      their eye movements optimally to maximize information acquisition for a variety
      of everyday tasks. Diseases such as macular degeneration can change visual
      sensory processing, introducing central vision loss (a scotoma). However, humans
      can learn to direct a new preferred retinal location to regions of interest for
      simple visual tasks. Whether such learned compensatory saccades are optimal and
      generalize to more complex tasks, which require integrating information across a
      large area of the visual field, is not well understood. Here, we explore the
      possible effects of central vision loss on the optimal saccades during a face
      identification task, using a gaze-contingent simulated scotoma. We show that a
      new foveated ideal observer with a central scotoma correctly predicts that the
      human optimal point of fixation to identify faces shifts from just below the eyes
      to one that is at the tip of the nose and another at the top of the forehead.
      However, even after 5000 trials, humans of both sexes surprisingly do not change
      their initial fixations to adapt to the new optimal fixation points to faces. In
      contrast, saccades do change for tasks such as object following and to a lesser
      extent during search. Our findings argue against a central brain motor
      compensatory mechanism that generalizes across tasks. They instead suggest task
      specificity in the learning of oculomotor plans in response to changes in front
      end sensory processing and the possibility of separate domain-specific
      representations of learned oculomotor plans in the brain.SIGNIFICANCE STATEMENT
      The mechanism by which humans adapt eye movements in response to central vision
      loss is still not well understood and carries importance for gaining a
      fundamental understanding of brain plasticity. We show that although humans adapt
      their eye movements for simpler tasks such as object following and search, these
      adaptations do not generalize to more complex tasks such as face identification.
      We provide the first computational model to predict where humans with central
      vision loss should direct their eye movements in face identification tasks, which
      could become a critical tool in making patient-specific recommendations. Based on
      these results, we suggest a novel theory for oculomotor learning: a distributed
      representation of learned eye-movement plans represented in domain-specific areas
      of the brain.

PMID- 29054880
TI  - Common Synaptic Input to Motor Neurons and Neural Drive to Targeted Reinnervated
      Muscles.
AB  - We compared the behavior of motor neurons innervating their physiological muscle
      targets with motor neurons from the same spinal segment whose axons were
      surgically redirected to remnant muscles (targeted muscle reinnervation). The
      objective was to assess whether motor neurons with nonphysiological innervation
      receive similar synaptic input and could be voluntary controlled as motor neurons
      with natural innervation. For this purpose, we acquired high-density EMG signals
      from the biceps brachii in 5 male transhumeral amputees who underwent targeted
      reinnervation of this muscle by the ulnar nerve and from the first dorsal
      interosseous muscle of 5 healthy individuals to investigate the natural
      innervation of the ulnar nerve. The same recordings were also performed from the
      biceps brachii muscle of additional 5 able-bodied individuals. The EMG signals
      were decomposed into discharges of motor unit action potentials. Motor neurons
      were progressively recruited for the full range of submaximal muscle activation
      in all conditions. Moreover, their discharge rate significantly increased from
      recruitment to target activation level in a similar way across the subject
      groups. Motor neurons across all subject groups received common synaptic input as
      identified by coherence analysis of their spike trains. However, the relative
      strength of common input in both the delta (0.5-5 Hz) and alpha (5-13 Hz) bands
      was significantly smaller for the surgically reinnervated motor neuron pool with
      respect to the corresponding physiologically innervated one. The results support
      the novel approach of motor neuron interfacing for prosthesis control and provide
      new insights into the role of afferent input on motor neuron
      activity.SIGNIFICANCE STATEMENT Targeted muscle reinnervation surgically
      redirects nerves that lost their target in the amputation into redundant muscles
      in the region of the stump. The study of the behavior of motor neurons following
      this surgery is needed for designing biologically inspired prosthetic control
      strategies. Moreover, targeted muscle reinnervation offers a human experimental
      framework for studying the control and behavior of motor neurons when changing
      their target innervated muscle fibers and sensory feedback. Here, we show that
      the control of motor neurons and their synaptic input, following reinnervation,
      was remarkably similar to that of the physiological innervation, although with
      reduced common drive at some frequencies. The results advance our knowledge on
      the role of sensory input in the generation of the neural drive to muscles and
      provide the basis for designing physiologically inspired methods for prosthesis
      control.

PMID- 29054881
TI  - Ablation of TFR1 in Purkinje Cells Inhibits mGlu1 Trafficking and Impairs Motor
      Coordination, But Not Autistic-Like Behaviors.
AB  - Group 1 metabotropic glutamate receptors (mGlu1/5s) are critical to synapse
      formation and participate in synaptic LTP and LTD in the brain. mGlu1/5 signaling
      alterations have been documented in cognitive impairment, neurodegenerative
      disorders, and psychiatric diseases, but underlying mechanisms for its modulation
      are not clear. Here, we report that transferrin receptor 1 (TFR1), a
      transmembrane protein of the clathrin complex, modulates the trafficking of mGlu1
      in cerebellar Purkinje cells (PCs) from male mice. We show that conditional knock
      out of TFR1 in PCs does not affect the cytoarchitecture of PCs, but reduces mGlu1
      expression at synapses. This regulation by TFR1 acts in concert with that by Rab8
      and Rab11, which modulate the internalization and recycling of mGlu1,
      respectively. TFR1 can bind to Rab proteins and facilitate their expression at
      synapses. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas parallel
      fiber-LTP and PC intrinsic excitability are not affected. Finally, we demonstrate
      that PC ablation of TFR1 impairs motor coordination, but does not affect social
      behaviors in mice. Together, these findings underscore the importance of TFR1 in
      regulating mGlu1 trafficking and suggest that mGlu1- and mGlu1-dependent parallel
      fiber-LTD are associated with regulation of motor coordination, but not autistic
      behaviors.SIGNIFICANCE STATEMENT Group 1 metabotropic glutamate receptor
      (mGlu1/5) signaling alterations have been documented in cognitive impairment,
      neurodegenerative disorders, and psychiatric diseases. Recent work suggests that
      altered mGlu1 signaling in Purkinje cells (PCs) may be involved in not only motor
      learning, but also autistic-like behaviors. We find that conditional knock-out of
      transferrin receptor 1 (TFR1) in PCs reduces synaptic mGlu1 by tethering Rab8 and
      Rab11 in the cytosol. PC ablation of TFR1 inhibits parallel fiber-PC LTD, whereas
      parallel fiber-PC LTP and PC intrinsic excitability are intact. Motor
      coordination is impaired, but social behaviors are normal in TFR1flox/flox;pCP2
      cre mice. Our data reveal a new regulator for trafficking and synaptic expression
      of mGlu1 and suggest that mGlu1-dependent LTD is associated with motor
      coordination, but not autistic-like behaviors.

PMID- 29054882
TI  - Parkinson's Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic
      Vesicle Trafficking in Ventral Midbrain Neurons.
AB  - Parkinson's disease (PD) is characterized pathologically by the selective loss of
      substantia nigra (SN) dopaminergic (DAergic) neurons. Recent evidence has
      suggested a role of LRRK2, linked to the most frequent familial PD, in regulating
      synaptic vesicle (SV) trafficking. However, the mechanism whereby LRRK2 mutants
      contribute to nigral vulnerability remains unclear. Here we show that the most
      common PD mutation LRRK2 G2019S impairs SV endocytosis in ventral midbrain (MB)
      neurons, including DA neurons, and the slowed endocytosis can be rescued by
      inhibition of LRRK2 kinase activity. A similar endocytic defect, however, was not
      observed in LRRK2 mutant neurons from the neocortex (hereafter, cortical neurons)
      or the hippocampus, suggesting a brain region-specific vulnerability to the
      G2019S mutation. Additionally, we found MB-specific impairment of SV endocytosis
      in neurons carrying heterozygous deletion of SYNJ1 (PARK20), a gene that is
      associated with recessive Parkinsonism. Combining SYNJ1+/- and LRRK2 G2019S does
      not exacerbate SV endocytosis but impairs sustained exocytosis in MB neurons and
      alters specific motor functions of 1-year-old male mice. Interestingly, we show
      that LRRK2 directly phosphorylates synaptojanin1 in vitro, resulting in the
      disruption of endophilin-synaptojanin1 interaction required for SV endocytosis.
      Our work suggests a merge of LRRK2 and SYNJ1 pathogenic pathways in deregulating
      SV trafficking in MB neurons as an underlying molecular mechanism of early PD
      pathogenesis.SIGNIFICANCE STATEMENT Understanding midbrain dopaminergic (DAergic)
      neuron-selective vulnerability in PD is essential for the development of targeted
      therapeutics. We report, for the first time, a nerve terminal impairment in SV
      trafficking selectively in MB neurons but not cortical neurons caused by two PARK
      genes: LRRK2 (PARK8) and SYNJ1 (PARK20). We demonstrate that the enhanced kinase
      activity resulting from the most frequent G2019S mutation in LRRK2 is the key to
      this impairment. We provide evidence suggesting that LRRK2 G2019S and SYNJ1 loss
      of function share a similar pathogenic pathway in deregulating DAergic neuron SV
      endocytosis and that they play additive roles in facilitating each other's
      pathogenic functions in PD.

PMID- 29054883
TI  - The role of patient and physician advocacy in reducing wait times for cancer
      care: a qualitative analysis.
AB  - BACKGROUND: There is growing interest in the role of physician as health
      advocate; however, few studies have documented advocacy from the patient's
      perspective. To address this gap, we examined the experiences of patients with
      cancer from the onset of symptoms to the start of treatment in Newfoundland and
      Labrador and aimed to describe wait times and efforts to improve timeliness of
      care from the patients' perspective. METHODS: We conducted qualitative interviews
      with 60 participants aged 19 years or more with breast, colorectal, lung or
      prostate cancer who were recruited from a survey of patients with cancer that was
      carried out as an earlier part of a larger study. All survey participants had
      received care at regional cancer clinics in Newfoundland and Labrador and were
      selected by means of purposive sampling based on their type of cancer, level of
      satisfaction with care and place of residence (urban, semiurban or rural).
      Interviews were transcribed verbatim and coded by means of a thematic approach.
      RESULTS: Participants described actions taken by themselves, their
      families/friends or members of their health care team to reduce their wait for a
      diagnosis and/or treatment. In all instances, participants believed that these
      actions resulted in more timely care. Participants reported that "insider
      knowledge" of health care professionals (whether friends, family members or
      members of the care team) was particularly valuable in reducing delays.
      INTERPRETATION: The use of advocacy was relatively commonplace. The role of
      advocacy, whether it originates from patient or caregiver, is important to ensure
      access to timely, good-quality cancer care.

PMID- 29054884
TI  - Assessing the extent of non-aggressive cancer in clinically detected stage I non
      small cell lung cancer.
AB  - BACKGROUND: Overdiagnosis among clinically detected lung cancers likely consists
      of cases that are non-aggressive and slowly progressive and will never
      disseminate, cause symptoms or be a threat to a subject's survival, even if
      untreated. In this study, we estimate the prevalence of non-aggressive lung
      cancers from a large, population-based cancer registry. METHODS: We identified
      individuals >=65 years with histologically confirmed, untreated stage I non-small
      cell lung cancers (NSCLCs) from the Surveillance, Epidemiology, and End Results
      Medicare registry. We estimated the rate of non-aggressive lung cancers by
      determining the point at which the cumulative lung cancer-specific survival curve
      no longer changed (ie, the slope approaches zero). At this point, there are no
      additional deaths due to progressive lung cancer observed among untreated
      patients after adjusting for deaths from competing risks (these long-term
      survivors can be considered 'non-aggressive cases). RESULTS: The overall rate of
      non-aggressive cancers among 2197 clinically detected cases of untreated stage I
      NSCLC was 2.4%, 95% CI: 1.0% to 3.8%. The rate of non-aggressive cancer was 1.9%
      (95% CI: 0.0% to 4.9%) for women and 2.4% (95% CI: 0.7% to 4.1%) for men
      (p=0.84). When stratifying by tumour size, non-aggressive cancer rates were 10.2%
      (95% CI: 0.0% to 29.3%), 2.1% (95% CI: 0.0% to 9.2%), 4.9% (95% CI: 0.0% to
      10.3%), 1.8% (95% CI: 0.0% to 5.2%) and 0.0% (95% CI: 0.0% to 1.0%) for tumour
      sizes <15 mm, 15-24 mm, 25-34 mm, 35-44 mm and >=45 mm, respectively. In
      comparison with the smallest tumour sizes (<15 mm), the rates of non-aggressive
      cancers were not statistically significantly different for tumour sizes 15-24 mm
      (p=0.36), 25-34 mm (p=0.57), 35-44 mm (p=0.38) and tumour sizes >45 mm (p=0.30).
      DISCUSSION: We found relatively low rates of non-aggressive cancers among
      clinically detected, stage I NSCLC regardless of sex or size. Our findings
      suggest that most clinically diagnosed early stage cancers should be treated with
      curative intent.

PMID- 29054885
TI  - Reference values for oxygen saturation from sea level to the highest human
      habitation in the Andes in acclimatised persons.
AB  - Oxygen saturation, measured by pulse oximetry (SpO2), is a vital clinical
      measure. Our descriptive, cross-sectional study describes SpO2 measurements from
      6289 healthy subjects from age 1 to 80 years at 15 locations from sea level up to
      the highest permanent human habitation. Oxygen saturation measurements are
      illustrated as percentiles. As altitude increased, SpO2 decreased, especially at
      altitudes above 2500 m. The increase in altitude had a significant impact on SpO2
      measurements for all age groups. Our data provide a reference range for expected
      SpO2 measurements in people from 1 to 80 years from sea level to the highest city
      in the world.

PMID- 29054886
TI  - The SSU processome interactome in Saccharomyces cerevisiae reveals novel protein
      subcomplexes.
AB  - Ribosome assembly is an evolutionarily conserved and energy intensive process
      required for cellular growth, proliferation, and maintenance. In yeast, assembly
      of the small ribosomal subunit (SSU) requires approximately 75 assembly factors
      that act in coordination to form the SSU processome, a 6 MDa ribonucleoprotein
      complex. The SSU processome is required for processing, modifying, and folding
      the preribosomal RNA (rRNA) to prepare it for incorporation into the mature SSU.
      Although the protein composition of the SSU processome has been known for some
      time, the interaction network of the proteins required for its assembly has
      remained poorly defined. Here, we have used a semi-high-throughput yeast two
      hybrid (Y2H) assay and coimmunoprecipitation validation method to produce a high
      confidence interactome of SSU processome assembly factors (SPAFs), providing
      essential insight into SSU assembly and ribosome biogenesis. Further, we used
      glycerol density-gradient sedimentation to reveal the presence of protein
      subcomplexes that have not previously been observed. Our work not only provides
      essential insight into SSU assembly and ribosome biogenesis, but also serves as
      an important resource for future investigations into how defects in biogenesis
      and assembly cause congenital disorders of ribosomes known as ribosomopathies.

PMID- 29054887
TI  - Introducing the new BTS Guideline: Management of non-tuberculous mycobacterial
      pulmonary disease (NTM-PD).
AB  - The new BTS Guidelines for the management of non-tuberculous mycobacterial
      pulmonary disease combine the best available evidence with expert consensus to
      generate a set of pragmatic Guidelines, published as a supplement to this issue
      of Thorax, to assist in the management of these challenging infections.

PMID- 29054888
TI  - Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer.
AB  - BACKGROUND: We aimed to disentangle genetic and environmental causes in lung
      cancer while considering smoking status. METHODS: Four Nordic twin cohorts (43
      512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had
      smoking data before cancer diagnosis. We used time-to-event analyses accounting
      for censoring and competing risk of death to estimate incidence, concordance risk
      and heritability of liability to develop lung cancer by smoking status. RESULTS:
      During a median of 28.5 years of follow-up, we recorded 1508 incident lung
      cancers. Of the 30 MZ and 28 DZ pairs concordant for lung cancer, nearly all were
      current smokers at baseline and only one concordant pair was seen among never
      smokers. Among ever smokers, the case-wise concordance of lung cancer, that is
      the risk before a certain age conditional on lung cancer in the co-twin before
      that age, was significantly increased compared with the cumulative incidence for
      both MZ and DZ pairs. This ratio, the relative recurrence risk, significantly
      decreased by age for MZ but was constant for DZ pairs. Heritability of lung
      cancer was 0.41 (95% CI 0.26 to 0.56) for currently smoking and 0.37 (95% CI 0.25
      to 0.49) for ever smoking pairs. Among smoking discordant pairs, the pairwise HR
      for lung cancer of the ever smoker twin compared to the never smoker co-twin was
      5.4 (95% CI 2.1 to 14.0) in MZ pairs and 5.0 (95% CI 3.2 to 7.9) in DZ pairs.
      CONCLUSIONS: The contribution of familial effects appears to decrease by age. The
      discordant pair analysis confirms that smoking causes lung cancer.

PMID- 29054890
TI  - Natural Killer T-cell Immunotherapy in Combination with Chemotherapy-Induced
      Immunogenic Cell Death Targets Metastatic Breast Cancer.
AB  - Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote
      cancer control. In previous studies, NKT-cell activation improved survival and
      antitumor immunity in a postsurgical mouse model of metastatic breast cancer.
      Herein, we investigated whether NKT-cell activation could be combined with
      chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and
      cyclophosphamide analogues enhanced the potential immunogenicity of 4T1 mammary
      carcinoma cells by increasing the expression of antigen-presenting molecules (MHC
      I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death
      markers (calreticulin, HMGB1, and ATP). In 4T1 primary tumor and postsurgical
      metastasis models, BALB/c mice were treated with cyclophosphamide or gemcitabine.
      NKT cells were then activated by transfer of dendritic cells loaded with the
      glycolipid antigen alpha-galactosylceramide (alpha-GalCer). Chemotherapeutic
      treatments did not impact NKT-cell activation but enhanced recruitment into
      primary tumors. Cyclophosphamide, gemcitabine, or alpha-GalCer-loaded dendritic
      cell monotherapies decreased tumor growth in the primary tumor model and reduced
      metastatic burden and prolonged survival in the metastasis model. Combining
      chemotherapeutics with NKT-cell activation therapy significantly enhanced
      survival, with surviving mice exhibiting attenuated tumor growth following a
      second tumor challenge. The frequency of myeloid-derived suppressor cells was
      reduced by gemcitabine, cyclophosphamide, or alpha-GalCer-loaded dendritic cell
      treatments; cyclophosphamide also reduced the frequency of regulatory T cells.
      Individual treatments increased immune cell activation, cytokine polarization,
      and cytotoxic responses, although these readouts were not enhanced further by
      combining therapies. These findings demonstrate that NKT-cell activation therapy
      can be combined with gemcitabine or cyclophosphamide to target tumor burden and
      enhance protection against tumor recurrence. Cancer Immunol Res; 5(12); 1086-97.
      (c)2017 AACR.

PMID- 29054891
TI  - Special issue on the effect of fear and stress on memory.

PMID- 29054892
TI  - Transthoracic Littre's hernia presenting with faecopneumothorax following
      perforation of the Meckel's diverticulum: a late complication of oesophagectomy.
AB  - A Littre's hernia is an unusual phenomenon where a Meckel's diverticulum
      protrudes through a potential abdominal opening. We wish to present a unique case
      of a 79-year-old man with respiratory distress following a fall from standing,
      initially managed as a haemothorax. After a chest drain was placed, bowel
      contents were drained from the pleural cavity and he was taken to theatre. He had
      a history of minimally invasive oesophagectomy for cancer and had subsequently
      developed a diaphragmatic hernia. A blind ending diverticulum with a perforation
      at its tip was found in the left oblique lung fissure that was subsequently
      confirmed histologically as a perforated Meckel's diverticulum. The patient had a
      prolonged stay on the intensive care unit with a left-sided empyema that was
      managed radiologically prior to discharge. Unfortunately 4 months
      postoperatively, he passed away from hospital-acquired pneumonia on a
      rehabilitation ward.

PMID- 29054893
TI  - Purpura Fulminans: A rare presentation of Streptococcus Pneumoniae infection.
AB  - A previously healthy man presented with fever for 2 days and rapidly progressive
      purpuric rash for 1 day. He progressed into hypotension, disseminated
      intravascular coagulation and refractory shock despite resuscitation and early
      antibiotic commencement. Blood culture grew Streptococcus pneumoniae This case
      report highlights the fact that purpura fulminans can be a rare presentation of
      S. pneumoniae infection as well.

PMID- 29054894
TI  - Mucopolysaccharidosis type IVA (Morquio A): a close differential diagnosis of
      spondylo-epiphyseal dysplasia.
AB  - Patients with mucopolysaccharidoses (MPS) have a plethora of multisystemic
      manifestations depending on the particular type, and atypical presentations are
      not uncommon. MPS type IVA (Morquio A syndrome) has predominant musculoskeletal
      system involvement and corneal clouding with normal intelligence and can be
      misdiagnosed as primary skeletal disorders in clinical practice. The absence of
      corneal clouding with normal urinary glycosaminoglycans (GAGs) level in a
      proportion of patients with MPS IVA makes the correct diagnosis even more
      challenging for physicians. Healthcare providers across specialties should have a
      high degree of suspicion for MPS IVA in all patients with suspected spondylo
      epiphyseal dysplasia as early diagnosis and early treatment significantly improve
      the clinical outcome and activity of daily living.

PMID- 29054895
TI  - Lemierre's syndrome variant of the gut.
AB  - Infectious suppurative thrombophlebitis of the portal venous system, referred to
      as pylephlebitis, is a rare complication of intra-abdominal inflammatory
      processes. Advances in diagnostics and antibiotics have improved survival, but
      mortality remains remarkably high even in the most recent literature. The
      majority of patients have concomitant bacteraemia on presentation most commonly
      with typical gastrointestinal (GI) organisms. On rare occasion, patients have
      culture positive Fusobacterium, which has recently been associated with occult GI
      and genitourinary malignancies. Here, we describe a patient presenting with
      pylephlebitis and Fusobacterium bacteraemia who responded well to medical
      therapy, review pertinent literature and discuss the benefits of screening
      endoscopy in this patient population.

PMID- 29054896
TI  - Metastatic melanoma of unknown primary in the temporalis muscle.
AB  - Melanomas are aggressive cancers that present as cutaneous, mucosal and ocular
      lesions with the ability to metastasise widely. There are, however, occasions
      where lesions are found in distant sites such as lymph nodes, viscera and
      subcutaneous tissues without clinically apparent skin involvement. This is known
      as metastatic melanoma of unknown primary (MUP). Its presentation in skeletal
      muscle is rare, and the available literature is sparse. This article presents an
      85-year-old woman with a MUP presenting in the right temporalis muscle, which was
      diagnosed with the aid of the ultrasound-guided core biopsy. The melanoma deposit
      was successfully excised, and no recurrence was identified. The patient is now
      under close follow-up.

PMID- 29054897
TI  - Lipoid proteinosis.

PMID- 29054898
TI  - Child with hypopyon.

PMID- 29054899
TI  - Lung adenocarcinoma metastastic lesion in the internal auditory meatus.
AB  - Metastasis to the cerebellopontine angle (CPA) or internal auditory meatus (IAM)
      is rare.We report a rare case of a 69-year-old woman with metastatic lung
      adenocarcinoma, who presented with 2 weeks history of left-sided hearing loss and
      progressively worsening vertigo. Examination revealed a left-sided facial nerve
      palsy while pure tone audiometry (PTA) showed a new left-sided deafness. MRI
      showed a new enhancing soft tissue lesion in the left IAM, highly suspicious of
      new metastases from her progressive lung cancer, which contributed to her neuro
      otological symptoms. Subsequent MRI scans 4 months later also showed new brain
      metastases. She continued to be managed with supportive palliative care in view
      of her extensive disease.

PMID- 29054900
TI  - Herpes zoster ophthalmicus in a 1-year-old child.

PMID- 29054901
TI  - A rare case of urethral prolapse in a postmenopausal woman.

PMID- 29054902
TI  - Chylous ascites in a patient with an overlap syndrome: a surprising response to
      rituximab.
AB  - The authors present a case of a 51-year-old woman with clinical diagnosis of
      mixed connective tissue disease and overlap systemic lupus erythematosus
      features, with a 6-month history of progressive painless abdominal distension. On
      examination, evident signs of ascites were present. Both the abdominal-pelvic
      ultrasound and CT scan confirmed a large amount of ascites. A diagnostic
      paracentesis was performed, which revealed typical features of chylous ascites
      (CA). An extensive diagnostic work-up led by a multidisciplinary team was
      performed, excluding malignancy, cirrhosis, infectious, as well as cardiac and
      primary lymphatic causes. The patient was kept under surveillance, with dietary
      therapy and periodic ascitic drainages. The hypothesis of an autoimmune cause for
      CA was considered by exclusion. Rituximab therapy was initiated and an excellent
      response was achieved, with reduction of the rate of accumulation of CA and an
      increase in quality of life of the patient.

PMID- 29054903
TI  - Barriers to safe abortion access: uterine rupture as complication of unsafe
      abortion in a Ugandan girl.
AB  - A 15-year-old girl at 18 weeks gestation by the last menstrual period presented
      to a rural Ugandan healthcare facility for termination of her pregnancy as a
      result of rape by her uncle. Skilled healthcare workers at the facility refused
      to provide the abortion due to fear of legal repercussions. The patient
      subsequently obtained an unsafe abortion by vaginal insertion of local herbs and
      sharp objects. She developed profuse vaginal bleeding and haemorrhagic shock. She
      was found to have uterine rupture and emergent hysterectomy was performed. Young
      and poor women are at high risk of unplanned pregnancy and subsequent mortality
      during pregnancy and childbirth. Unsafe abortion is a leading and entirely
      preventable cause of maternal mortality worldwide. Multiple barriers restrict
      access to safe abortions including social and moral stigma, gender-based power
      imbalances, inadequate contraceptive use and sexual education, high cost and poor
      availability, and restrictive abortion laws.

PMID- 29054904
TI  - Severe crush injury to the lower extremity after a snowmobile accident in rural
      Greenland.

PMID- 29054905
TI  - Ultra-wide imaging in a case of retinal vasculitis with macular star.

PMID- 29054906
TI  - Shotgun wound to the leg: strategies in managing acute arterial injury and bullet
      emboli to the heart and lungs.

PMID- 29054907
TI  - Secondary aortoduodenal fistula and the unrecognised herald bleed.
AB  - A 65-year-old man with history of aortobifemoral surgery 4 years ago was admitted
      to hospital after sudden abdominal pain. Initially misdiagnosed as renal colic,
      he was treated with analgesics, and while on observation he started with
      haematemesis, rapidly responding to volume infusion. Upper gastrointestinal
      endoscopy showed fresh blood in the stomach with no visible active bleeding. CT
      scan showed an important contrast extravasation from the aorta to the third
      duodenal portion, restarting haemodynamic instability and a cardiac arrest.
      Cardiopulmonary resuscitation (CPR) manoeuvres followed by intense fluid
      resuscitation and urgent laparotomy with a fast transabdominal supracoeliac
      aortic clamping was performed. After multiple blood and plasma unit transfusion
      and intravenous norepinephrine, two more cardiac arrests were recovered.
      Unfortunately, after aggressive management, the patient rapidly deteriorated and
      deceased on the table. Aortoduodenal fistula is a rare entity causing life
      threatening bleeding. Its diagnosis requires high clinical suspicion and surgery
      offers the only hope for survival.

PMID- 29054908
TI  - Strange case of dimorphic skin rash in a patient with cirrhosis: atypical herpes
      simplex and sweet's syndrome.
AB  - A middle-aged man with decompensated cirrhosis and a dimorphic multisite skin
      rash is diagnosed with rare atypical herpes simplex infection, manifesting
      Sweet's syndrome (SS) in the absence of other described associations. SS, an
      acute febrile neutrophilic dermatosis, has three common forms-classical or
      idiopathic, malignancy associated and drug induced. Systemic autoimmune,
      connective tissue diseases and infections are also strong associations. The
      latter is commonly described in Gram-positive bacteria, salmonellosis and
      Yersinia Herpes infections are a rare cause of SS, reported only thrice in
      literature, one with concomitant lupus, the second with associated mycobacterial
      infection and third, in metastatic breast disease in contrast to our patient.
      Atypical rash, especially if dimorphic, warrants histopathological evaluation to
      confirm underlying disease.

PMID- 29054909
TI  - Renal cell carcinoma metastases to the maxillary sinus.
AB  - Metastasis of renal cell carcinoma (RCC) to the head and neck region is rare. We
      report the case of a 65-year-old man with history of RCC, presented 7 years after
      nephrectomy, adrenalectomy and lung metastasectomy for his primary tumour, with
      symptoms of nasal obstruction, postnasal drip, productive cough and pressure
      sensation in the left maxillary sinus. CT revealed a unilateral, irregular
      opacification in the left maxillary sinus with bony erosion of the infraorbital
      canal wall. A yellow cystic lesion was completely removed from the maxillary
      sinus during functional endoscopic sinus surgery and histopathological analysis
      confirmed the diagnosis of a metastatic RCC. Patient continued to be managed with
      his pre-existing treatment for advanced RCC.

PMID- 29054910
TI  - Mesh campaigners are dismayed by minister's blunder over NICE guidance.

PMID- 29054912
TI  - New primary care model expands to 200 sites across England.

PMID- 29054911
TI  - Ixazomib significantly prolongs progression-free survival in high-risk
      relapsed/refractory myeloma patients.
AB  - Certain cytogenetic abnormalities are known to adversely impact outcomes in
      patients with multiple myeloma (MM). The phase 3 TOURMALINE-MM1 study
      demonstrated a significant improvement in progression-free survival (PFS) with
      ixazomib-lenalidomide-dexamethasone (IRd) compared with placebo-lenalidomide
      dexamethasone (placebo-Rd). This preplanned analysis assessed the efficacy and
      safety of IRd vs placebo-Rd according to cytogenetic risk, as assessed using
      fluorescence in situ hybridization. High-risk cytogenetic abnormalities were
      defined as del(17p), t(4;14), and/or t(14;16); additionally, patients were
      assessed for 1q21 amplification. Of 722 randomized patients, 552 had cytogenetic
      results; 137 (25%) had high-risk cytogenetic abnormalities and 172 (32%) had 1q21
      amplification alone. PFS was improved with IRd vs placebo-Rd in both high-risk
      and standard-risk cytogenetics subgroups: in high-risk patients, the hazard ratio
      (HR) was 0.543 (95% confidence interval [CI], 0.321-0.918; P = .021), with median
      PFS of 21.4 vs 9.7 months; in standard-risk patients, HR was 0.640 (95% CI, 0.462
      0.888; P = .007), with median PFS of 20.6 vs 15.6 months. This PFS benefit was
      consistent across subgroups with individual high-risk cytogenetic abnormalities,
      including patients with del(17p) (HR, 0.596; 95% CI, 0.286-1.243). PFS was also
      longer with IRd vs placebo-Rd in patients with 1q21 amplification (HR, 0.781; 95%
      CI, 0.492-1.240), and in the "expanded high-risk" group, defined as those with
      high-risk cytogenetic abnormalities and/or 1q21 amplification (HR, 0.664; 95% CI,
      0.474-0.928). IRd demonstrated substantial benefit compared with placebo-Rd in
      relapsed and/or refractory MM (RRMM) patients with high-risk and standard-risk
      cytogenetics, and improves the poor PFS associated with high-risk cytogenetic
      abnormalities. This trial was registered at www.clinicaltrials.gov as
      #NCT01564537.

PMID- 29054914
TI  - Flow diversion for the treatment of posterior inferior cerebellar artery
      aneurysms: a novel classification and strategies.
AB  - BACKGROUND: The pipeline embolization device (PED) is frequently used in the
      treatment of anterior circulation aneurysms, especially around the carotid
      siphon, with generally excellent results. However, treatment of posterior
      inferior cerebellar artery (PICA) aneurysms with flow diversion (FD) has not been
      specifically described or discussed. While there are reports of treating PICA
      aneurysms using placement of FD stents in the vertebral artery, there are no
      reports of treating these lesions by placement of flow diverting stents in the
      PICA vessel itself. Due to the unique anatomy and morphology of these aneurysms,
      it requires special attention. We assessed our multi-institutional experience
      treating these lesions, including the first reported cases of the PED placed
      within the PICA. METHODS: Institutional databases of neuroendovascular procedures
      were reviewed for cases of intracranial aneurysms treated with the PED. Patient
      and aneurysm data as well as angiographic imaging were reviewed for all cases of
      PICA aneurysms treated with the PED. PICA aneurysms were defined as aneurysms
      that involved the PICA. Vertebral aneurysms without disease in the PICA were
      excluded from the study. RESULTS: 10 PICA aneurysms were treated during the study
      period. These were classified based on their morphology and location into two
      main types and five total subtypes for consideration of treatment with flow
      diversion. All aneurysms were successfully treated, with 8/10 completely
      obliterated and 2 with a partial reduction in size. Three patients had the PED
      placed entirely in the PICA and no patient suffered from a medullary or
      cerebellar stroke. All PEDs were patent and all patients were independent at the
      last follow-up. CONCLUSIONS: The PED may be used successfully to treat select
      aneurysms of the PICA. We present the first described cases of successful PED
      treatment of PICA aneurysms with direct placement of the PED in the PICA vessel
      itself. The proposed classification system aids in that selection.

PMID- 29054913
TI  - Treatment of recurrent aneurysms using the Woven EndoBridge (WEB): anatomical and
      clinical results.
AB  - BACKGROUND: The safety and efficacy of the Woven EndoBridge (WEB) for the
      treatment of naive intracranial aneurysms has been confirmed. PURPOSE: To analyze
      the safety and efficacy of the WEB in the treatment of recurrent aneurysms.
      METHODS: Anatomical and clinical results in consecutive patients with a recurrent
      aneurysm, who were treated using the WEB device in two French neurointerventional
      centers, were evaluated. RESULTS: Seventeen patients with 17 aneurysms were
      included. Treatment was feasible in 16 patients. In seven patients (41.2%),
      ancillary devices were used. Permanent morbidity due to a thromboembolic
      complication occurred in one patient (5.9%). There was no mortality. Follow-up
      angiographic studies were available for 15 patients after a mean of 12.1+/-6.1
      months. Rates of complete occlusion, neck remnant, and aneurysm remnant were
      33.3%, 40.0%, and 26.7%, respectively. CONCLUSIONS: Treatment of recurrent
      aneurysms using the WEB device may be reasonably safe and effective.

PMID- 29054915
TI  - Prevalence of sleep apnoea and capnographic detection of nocturnal
      hypoventilation in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: This retrospective study aimed to investigate whether overnight
      oxymetry and early morning blood gas analysis predict nocturnal hypoventilation
      (NH) as reflected by night-time hypercapnia in patients with amyotrophic lateral
      sclerosis (ALS). In addition, prevalence and clinical determinants of sleep
      apnoea in ALS were evaluated. METHODS: In 250 patients with non-ventilated ALS,
      transcutaneous capnometry was performed along with polysomnography or polygraphy
      and early morning blood gases. RESULTS: 123 patients were female, and 84 patients
      had bulbar-onset ALS. 40.0% showed NH, and an apnoea-hypopnoea index (AHI)
      >5/hour was found in 45.6%. In 22.3%, sleep apnoea and NH coincided. The
      obstructive apnoea index was significantly higher than the central apnoea index
      (p<0.0001). Both NH and sleep apnoea were significantly more common in male than
      in female patients. Sleep apnoea and AHI were associated with better bulbar
      function. Desaturation time (t<90%) and transcutaneous CO2 were negatively
      correlated with upright vital capacity. Early morning base excess (EMBE),
      bicarbonate and t<90% were independent predictors of NH. However, among 100
      patients with NH, 31 were missed by t<90% >5 min and 17 were not identified when
      EMBE >3 mmol/L and t<90% >5 min were combined. CONCLUSION: In ALS, sleep apnoea
      is common and often accompanies NH. It is mainly obstructive, and central apnoea
      appears to be clinically irrelevant. Polygraphy or oxymetry alone are not
      sufficient to uncover NH. Combination of EMBE and t<90% may increase sensitivity,
      but transcutaneous capnography is strongly recommended for reliable detection of
      NH in patients with ALS.

PMID- 29054916
TI  - Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in
      probable cerebral amyloid angiopathy without lobar haemorrhage.
AB  - INTRODUCTION: Acute non-traumatic convexity subarachnoid haemorrhage (cSAH) is
      increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated:
      (a) the overlap between acute cSAH and cortical superficial siderosis-a new CAA
      haemorrhagic imaging signature and (b) whether acute cSAH presents with
      particular clinical symptoms in patients with probable CAA without lobar
      intracerebral haemorrhage. METHODS: MRI scans of 130 consecutive patients meeting
      modified Boston criteria for probable CAA were analysed for cortical superficial
      siderosis (focal, <=3 sulci; disseminated, >=4 sulci), and key small vessel
      disease markers. We compared clinical, imaging and cortical superficial siderosis
      topographical mapping data between subjects with versus without acute cSAH, using
      multivariable logistic regression. RESULTS: We included 33 patients with probable
      CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with
      acute cSAH were more commonly presenting with transient focal neurological
      episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH.
      Patients with acute cSAH were also more often clinically presenting with
      transient focal neurological episodes compared with cortical superficial
      siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001).
      Cortical superficial siderosis prevalence (but no other CAA severity markers) was
      higher among patients with cSAH versus those without, especially disseminated
      cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic
      regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8,
      p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to
      50.6, p=0.001) were independently associated with acute cSAH. CONCLUSIONS: This
      probable CAA cohort provides additional evidence for distinct disease phenotypes,
      determined by the presence of cSAH and cortical superficial siderosis.

PMID- 29054918
TI  - Non-invasive in vivo neuropathology of the C9orf72-related ALS-FTD syndrome.

PMID- 29054917
TI  - Longitudinal diffusion imaging across the C9orf72 clinical spectrum.
AB  - INTRODUCTION: Discrepancies between diffusion tensor imaging (DTI) findings and
      functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to
      symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction
      affecting non-motor regions of the brain. Carriers of expansion mutations in the
      C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from
      ALS to frontotemporal dementia, present an opportunity to evaluate the
      relationship between symptom heterogeneity and DTI changes. METHODS: Twenty-eight
      C9orf72 mutation carriers with varied cognitive and motor symptoms underwent
      clinical evaluation and DTI imaging. Twenty returned for two or more follow-up
      evaluations. Each evaluation included motor, executive and behavioural scales and
      disease staging using the King's college staging system. RESULTS: Widespread
      reduction of white matter integrity occurred in C9orf72 mutation carriers
      compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King's
      stage correlated with DTI measures of the corticospinal tract and mid-callosum.
      Cognitive and behavioural scores correlated with diffusion measures of frontal
      white matter. King's stage, but not ALSFRS-R, correlated with anterior callosum
      DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to
      posterior, and from deep to superficial subcortical white matter. In C9orf72
      carriers with ALS or ALS-FTD, changes in corticospinal tractography measures
      correlated with changes in ALSFRS-R. CONCLUSION: Discrepancies between DTI
      findings and clinical measures of disease severity in ALS may partly be accounted
      for by cognitive-behavioural deficits affecting extramotor white matter tracts.
      Both ALSFRS-R and King's stage correlated with corticospinal DTI measures. Group
      level DTI changes could be detected over 6 months.

PMID- 29054919
TI  - Comparison of elevated phosphorylated neurofilament heavy chains in serum and
      cerebrospinal fluid of patients with amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Phosphorylated neurofilament heavy chain (pNfH) levels are elevated in
      cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS).
      Instead of CSF, we explored blood as an alternative source to measure pNfH in
      patients with ALS. METHODS: In this single centre retrospective study, 85
      patients with ALS, 215 disease controls (DC) and 31 ALS mimics were included.
      Individual serum pNfH concentrations were correlated with concentrations in CSF
      and with several clinical parameters. The performance characteristics of pNfH in
      CSF and serum of patients with ALS and controls were calculated and compared
      using receiver operating characteristic (ROC) curves. RESULTS: CSF and serum pNfH
      concentrations in patients with ALS correlated well (r=0.652, p<0.0001) and were
      significantly increased compared with DC (p<0.0001) and ALS mimics (p<0.0001).
      CSF pNfH outperformed serum pNfH in discriminating patients with ALS from DC and
      ALS mimics (difference between area under the ROC curves: p=0.0001 and p=0.0005;
      respectively). Serum pNfH correlated inversely with symptom duration (r=-0.315,
      p=0.0033). CSF and serum pNfH were lower when the disease progression rate was
      slower (r=0.279, p<0.01 and r=0.289, p<0.01; respectively). Unlike CSF, serum
      pNfH did not correlate with the burden of clinical and electromyographic motor
      neuron dysfunction. CONCLUSIONS: CSF and serum pNfH concentrations are elevated
      in patients with ALS and correlate with the disease progression rate. Moreover,
      CSF pNfH correlates with the burden of motor neuron dysfunction. Our findings
      encourage further pursuit of CSF and serum pNfH concentrations in the diagnostic
      pathway of patients suspected to have ALS.

PMID- 29054920
TI  - CSF beta-amyloid and white matter damage: a new perspective on Alzheimer's
      disease.
AB  - OBJECTIVE: To assess the connection between amyloid pathology and white matter
      (WM) macrostructural and microstructural damage in demented patients compared
      with controls. METHODS: Eighty-five participants were recruited: 65 with newly
      diagnosed Alzheimer's disease (AD), non-AD dementia or mild cognitive impairment
      and 20 age-matched and sex-matched healthy controls. beta-amyloid1-42 (Abeta)
      levels were determined in cerebrospinal fluid (CSF) samples from all patients and
      five controls. Among patients, 42 had pathological CSF Abeta levels (Abeta(+)),
      while 23 had normal CSF Abeta levels (Abeta(-)). All participants underwent
      neurological examination, neuropsychological testing and brain MRI. We used T2
      weighted scans to quantify WM lesion loads (LLs) and diffusion-weighted images to
      assess their microstructural substrate. Non-parametric statistical tests were
      used for between-group comparisons and multiple regression analyses. RESULTS: We
      found an increased WM-LL in Abeta(+) compared with both, healthy controls
      (p=0.003) and Abeta(-) patients (p=0.02). Interestingly, CSF Abeta concentration
      was the best predictor of patients' WM-LL (r=-0.30, p<0.05) when using age as a
      covariate. Lesion apparent diffusion coefficient value was higher in all patients
      than in controls (p=0.0001) and correlated with WM-LL (r=0.41, p=0.001). In
      Abeta(+), WM-LL correlated with WM microstructural damage in the left
      peritrigonal WM (p<0.0001). CONCLUSIONS: WM damage is crucial in AD pathogenesis.
      The correlation between CSF Abeta levels and WM-LL suggests a direct link between
      amyloid pathology and WM macrostructural and microstructural damage.

PMID- 29054921
TI  - Enhancing Diversity in Undergraduate Science: Self-Efficacy Drives Performance
      Gains with Active Learning.
AB  - Efforts to retain underrepresented minority (URM) students in science,
      technology, engineering, and mathematics (STEM) have shown only limited success
      in higher education, due in part to a persistent achievement gap between students
      from historically underrepresented and well-represented backgrounds. To test the
      hypothesis that active learning disproportionately benefits URM students, we
      quantified the effects of traditional versus active learning on student academic
      performance, science self-efficacy, and sense of social belonging in a large
      (more than 250 students) introductory STEM course. A transition to active
      learning closed the gap in learning gains between non-URM and URM students and
      led to an increase in science self-efficacy for all students. Sense of social
      belonging also increased significantly with active learning, but only for non-URM
      students. Through structural equation modeling, we demonstrate that, for URM
      students, the increase in self-efficacy mediated the positive effect of active
      learning pedagogy on two metrics of student performance. Our results add to a
      growing body of research that supports varied and inclusive teaching as one
      pathway to a diversified STEM workforce.

PMID- 29054922
TI  - Protein Turnover Measurements in Human Serum by Serial Immunoaffinity LC-MS/MS.
AB  - BACKGROUND: The half-life of target proteins is frequently an important parameter
      in mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of
      biotherapeutics. Clinical studies for accurate measurement of physiologically
      relevant protein turnover can reduce the uncertainty in PK/PD model-based
      predictions, for example, of the therapeutic dose and dosing regimen in first-in
      human clinical trials. METHODS: We used a targeted mass spectrometry work flow
      based on serial immunoaffinity enrichment ofmultiple human serum proteins from a
      [5,5,5-2H3]-L-leucine tracer pulse-chase study in healthy volunteers. To confirm
      the reproducibility of turnover measurements from serial immunoaffinity
      enrichment, multiple aliquots from the same sample set were subjected to protein
      turnover analysis in varying order. Tracer incorporation was measured by multiple
      reaction-monitoring mass spectrometry and target turnover was calculated using a
      four-compartment pharmacokinetic model. RESULTS: Five proteins of clinical or
      therapeutic relevance including soluble tumor necrosis factor receptor
      superfamily member 12A, tissue factor pathway inhibitor, soluble interleukin 1
      receptor like 1, soluble mucosal addressin cell adhesion molecule 1, and muscle
      specific creatine kinase were sequentially subjected to turnover analysis from
      the same human serum sample. Calculated half-lives ranged from 5-15 h; however,
      no tracer incorporation was observed for mucosal addressin cell adhesion molecule
      1. CONCLUSIONS: The utility of clinical pulse-chase studies to investigate
      protein turnover can be extended by serial immunoaffinity enrichment of target
      proteins. Turnover analysis from serum and subsequently from remaining
      supernatants provided analytical sensitivity and reproducibility for multiple
      human target proteins in the same sample set, irrespective of the order of
      analysis.

PMID- 29054923
TI  - Activity of the Calcineurin Pathway in Patients on the Liver Transplantation
      Waiting List: Factors of Variability and Response to Tacrolimus Inhibition.
AB  - BACKGROUND: We sought to evaluate, in patients on a liver transplantation waiting
      list, potential biomarkers of the base calcineurin pathway activity with use of a
      new model of nonstimulated peripheral blood mononuclear cells (PBMC) and ex vivo
      response to tacrolimus (TAC). METHODS: The calcineurin pathway activity was
      explored ex vivo in stimulated and nonstimulated PBMC from 19 patients. The
      inhibition of NFAT1 translocation to PBMC nuclei, expression of intracellular IL
      2, and membrane CD25 in different T-cell subsets were measured by multiparametric
      flow cytometry before and after exposure to TAC. We also studied the influence on
      the individual response of polymorphisms in 3 key genes of the calcineurin
      pathway: PPIA, PPP3CA, and IL2RA. RESULTS: All pharmacodynamics profiles closely
      fitted an I/Imax sigmoid model. Interindividual variability was higher in
      nonstimulated than in stimulated conditions, as well as in the presence of TAC.
      IL-2+CD8+ cells at TAC Imax showed the highest interindividual variability,
      suggesting its usefulness as a biomarker of individual TAC effects integrating
      many different sources of regulation and variability. Moreover, in the absence of
      TAC, patients with end-stage liver disease exhibited lower NFAT1 translocation
      and T-cell activation than healthy volunteers from a previous study under similar
      conditions. Multivariate statistical analysis showed strong and significant
      associations between TAC pharmacodynamic parameters and 2 polymorphisms in the
      gene-coding cyclophilin A (rs8177826 and rs6850). CONCLUSIONS: We show the
      feasibility of using nonstimulated PBMCs to explore the calcineurin pathway under
      more physiologic conditions and point toward potential biomarkers for TAC
      pharmacodynamic monitoring. ClinicalTrials.gov Identifier: NCT01760356.

PMID- 29054924
TI  - Pharmacotherapy for Patients with Obesity.
AB  - BACKGROUND: Although pharmacotherapy is not the cornerstone of obesity treatment,
      it is a valuable tool that could be considered for patients who have not had
      adequate benefit from lifestyle interventions or who have difficulty maintaining
      initial weight loss over longer periods. CONTENT: This review focuses on the role
      of antiobesity drugs, the mechanisms by which the drugs work, potential
      pharmacological targets in the neural control of food intake and regulation of
      body weight, the history of antiobesity drugs, a summary of efficacy and safety
      data from clinical trials, and the clinical application of pharmacotherapy.
      Currently, 5 approved drug therapies are available in the US for long-term weight
      management, with only 2 of these meeting the stronger Food and Drug
      Administration (FDA) criteria of 5% weight loss relative to a placebo after 1
      year and others receiving approval based on the categorical criterion of the
      proportions of patients achieving 5% weight loss. Interpretation of the results
      of clinical trials conducted before regulatory agency approval is limited by high
      dropout rates; thus, the results might not be replicable in clinical practice
      settings. Many patients who are suitable candidates for pharmacotherapy are not
      using the new drugs due to lack of insurance coverage and high out-of-pocket
      costs. SUMMARY: With the availability of 4 new drugs since 2012, clinicians in
      the US now have more tools for long-term weight management. The quality of
      pharmacotherapy clinical investigations needs considerable improvement. Future
      research should focus on examining the mediators and moderators of response.

PMID- 29054925
TI  - Platelet mitochondrial dysfunction and the correlation with human diseases.
AB  - The platelet is considered as an accessible and valuable tool to study
      mitochondrial function, owing to its greater content of fully functional
      mitochondria compared with other metabolically active organelles. Different lines
      of studies have demonstrated that mitochondria in platelets have function far
      more than thrombogenesis regulation, and beyond hemostasis, platelet
      mitochondrial dysfunction has also been used for studying mitochondrial-related
      diseases. In this review, the interplay between platelet mitochondrial
      dysfunction and oxidative stress, mitochondrial DNA lesions, electron transfer
      chain impairments, mitochondrial apoptosis and mitophagy has been outlined.
      Meanwhile, considerable efforts have been made towards understanding the role of
      platelet mitochondrial dysfunction in human diseases, such as diabetes mellitus,
      sepsis and neurodegenerative disorders. Alongside this, we have also articulated
      our perspectives on the development of potential biomarkers of platelet
      mitochondrial dysfunction in mitochondrial-related diseases.

PMID- 29054926
TI  - Biomolecular coevolution and its applications: Going from structure prediction
      toward signaling, epistasis, and function.
AB  - Evolution leads to considerable changes in the sequence of biomolecules, while
      their overall structure and function remain quite conserved. The wealth of
      genomic sequences, the 'Biological Big Data', modern sequencing techniques
      provide allows us to investigate biomolecular evolution with unprecedented
      detail. Sophisticated statistical models can infer residue pair mutations
      resulting from spatial proximity. The introduction of predicted spatial
      adjacencies as constraints in biomolecular structure prediction workflows has
      transformed the field of protein and RNA structure prediction toward accuracies
      approaching the experimental resolution limit. Going beyond structure prediction,
      the same mathematical framework allows mimicking evolutionary fitness landscapes
      to infer signaling interactions, epistasis, or mutational landscapes.

PMID- 29054927
TI  - The C-terminal region of A-kinase anchor protein 350 (AKAP350A) enables formation
      of microtubule-nucleation centers and interacts with pericentriolar proteins.
AB  - Microtubules in animal cells assemble (nucleate) from both the centrosome and the
      cis-Golgi cisternae. A-kinase anchor protein 350 kDa (AKAP350A, also called
      AKAP450/CG-NAP/AKAP9) is a large scaffolding protein located at both the
      centrosome and Golgi apparatus. Previous findings have suggested that AKAP350 is
      important for microtubule dynamics at both locations, but how this scaffolding
      protein assembles microtubule nucleation machinery is unclear. Here, we found
      that overexpression of the C-terminal third of AKAP350A, enhanced GFP
      AKAP350A(2691-3907), induces the formation of multiple microtubule-nucleation
      centers (MTNCs). Nevertheless, these induced MTNCs lacked "true" centriole
      proteins, such as Cep135. Mapping analysis with AKAP350A truncations demonstrated
      that AKAP350A contains discrete regions responsible for promoting or inhibiting
      the formation of multiple MTNCs. Moreover, GFP-AKAP350A(2691-3907) recruited
      several pericentriolar proteins to MTNCs, including gamma-tubulin, pericentrin,
      Cep68, Cep170, and Cdk5RAP2. Proteomic analysis indicated that Cdk5RAP2 and
      Cep170 both interact with the microtubule nucleation-promoting region of
      AKAP350A, whereas Cep68 interacts with the distal C-terminal AKAP350A region.
      Yeast two-hybrid assays established a direct interaction of Cep170 with AKAP350A.
      Super-resolution and deconvolution microscopy analyses were performed to define
      the association of AKAP350A with centrosomes, and these studies disclosed that
      AKAP350A spans the bridge between centrioles, co-localizing with rootletin and
      Cep68 in the linker region. siRNA-mediated depletion of AKAP350A caused
      displacement of both Cep68 and Cep170 from the centrosome. These results suggest
      that AKAP350A acts as a scaffold for factors involved in microtubule nucleation
      at the centrosome and coordinates the assembly of protein complexes associating
      with the intercentriolar bridge.

PMID- 29054928
TI  - The type II transmembrane serine protease matriptase cleaves the amyloid
      precursor protein and reduces its processing to beta-amyloid peptide.
AB  - Recent studies have reported that many proteases, besides the canonical alpha-,
      beta-, and gamma-secretases, cleave the amyloid precursor protein (APP) and
      modulate beta-amyloid (Abeta) peptide production. Moreover, specific APP isoforms
      contain Kunitz protease-inhibitory domains, which regulate the proteolytic
      activity of serine proteases. This prompted us to investigate the role of
      matriptase, a member of the type II transmembrane serine protease family, in APP
      processing. Using quantitative RT-PCR, we detected matriptase mRNA in several
      regions of the human brain with an enrichment in neurons. RNA sequencing data of
      human dorsolateral prefrontal cortex revealed relatively high levels of
      matriptase RNA in young individuals, whereas lower levels were detected in older
      individuals. We further demonstrate that matriptase and APP directly interact
      with each other and that matriptase cleaves APP at a specific arginine residue
      (Arg-102) both in vitro and in cells. Site-directed (Arg-to-Ala) mutagenesis of
      this cleavage site abolished matriptase-mediated APP processing. Moreover, we
      observed that a soluble, shed matriptase form cleaves endogenous APP in SH-SY5Y
      cells and that this cleavage significantly reduces APP processing to Abeta40. In
      summary, this study identifies matriptase as an APP-cleaving enzyme, an activity
      that could have important consequences for the abundance of Abeta and in
      Alzheimer's disease pathology.

PMID- 29054929
TI  - Mitogen- and stress-activated protein kinase 1 is required for gonadotropin
      releasing hormone-mediated activation of gonadotropin alpha-subunit expression.
AB  - Pituitary gonadotropin hormones are regulated by gonadotropin-releasing hormone
      (GnRH) via MAPK signaling pathways that stimulate gene transcription of the
      common alpha-subunit (Cga) and the hormone-specific beta-subunits of
      gonadotropin. We have reported previously that GnRH-induced activities at these
      genes include various histone modifications, but we did not examine histone
      phosphorylation. This modification adds a negative charge to residues of the
      histone tails that interact with the negatively charged DNA, is associated with
      closed chromatin during mitosis, but is increased at certain genes for
      transcriptional activation. Thus, the functions of this modification are unclear.
      We initially hypothesized that GnRH might induce phosphorylation of Ser-10 in
      histone 3 (H3S10p) as part of its regulation of gonadotropin gene expression,
      possibly involving cross-talk with H3K9 acetylation. We found that GnRH increases
      the levels of both modifications around the Cga gene transcriptional start site
      and that JNK inhibition dramatically reduces H3S10p levels. However, this
      modification had only a minor effect on Cga expression and no effect on H3K9ac.
      GnRH also increased H3S28p and H3K27ac levels and also those of activated mitogen
      and stress-activated protein kinase 1 (MSK1). MSK1 inhibition dramatically
      reduced H3S28p levels in untreated and GnRH-treated cells and also affected
      H3K27ac levels. Although not affecting basal Cga expression, MSK1/2 inhibition
      repressed GnRH activation of Cga expression. Moreover, ChIP analysis revealed
      that GnRH-activated MSK1 targets the first nucleosome just downstream from the
      TSS. Given that the elongating RNA polymerase II (RNAPII) stalls at this well
      positioned nucleosome, GnRH-induced H3S28p, possibly in association with H3K27ac,
      would facilitate the progression of RNAPII.

PMID- 29054930
TI  - The transcription factor MEF2A fine-tunes gene expression in the atrial and
      ventricular chambers of the adult heart.
AB  - The distinct morphological and functional properties of the cardiac chambers
      arise from an elaborate developmental program involving cell lineage
      determination, morphogenesis, and dynamic spatiotemporal gene expression
      patterns. Although a number of transcription factors have been identified for
      proper gene regulation in the chambers, the complete transcriptional network that
      controls these patterns remains poorly defined. Previous studies have implicated
      the MEF2C transcription factor in the regulation of chamber-restricted enhancers.
      To better understand the mechanisms of MEF2-mediated regional gene regulation in
      the heart, we took advantage of MEF2A knock-out (KO) mice, a model that displays
      a predominantly ventricular chamber phenotype. Transcriptomic analysis of atrial
      and ventricular tissue from adult MEF2A KO hearts revealed a striking difference
      in chamber gene expression, with a larger proportion of dysregulated genes in the
      atrial chambers. Canonical pathway analysis of genes preferentially dysregulated
      in the atria and ventricles revealed distinct MEF2A-dependent cellular processes
      in each cardiac chamber. In the atria, MEF2A regulated genes involved in fibrosis
      and adhesion, whereas in the ventricles, it controlled inflammation and
      endocytosis. Finally, analysis of transcription factor-binding site motifs of
      differentially dysregulated genes uncovered distinct MEF2A co-regulators for the
      atrial and ventricular gene sets, and a subset of these was found to cooperate
      with MEF2A. In conclusion, our results suggest a mechanism in which MEF2
      transcriptional activity is differentially recruited to fine-tune gene expression
      levels in each cardiac chamber. This regulatory mechanism ensures optimal output
      of these gene products for proper physiological function of the atrial and
      ventricular chambers.

PMID- 29054932
TI  - Improving paediatric residents' knowledge and perspectives regarding the insulin
      pump using a novel educational workshop.
AB  - OBJECTIVES: As a pilot study, we aimed to investigate the knowledge and
      perceptions of categorical paediatric residents (RES) at our institution
      regarding insulin pumps (IPs) and the impact following a targeted workshop.
      METHODS: All RES at our institution in attendance at a routine noon conference
      participated in a workshop, completing an anonymous survey before and right after
      the intervention to evaluate knowledge, attitudes and self-reported comfort
      regarding IPs. The workshop consisted of a didactic lecture followed by an
      insulin pump (IP) device demonstration of three commonly available brands.
      Knowledge score (KS) was calculated for each RES based on the total correct
      responses. Attitudes were assessed via 5-point Likert scale. Frequencies, t-test
      and McNemar tests were used to analyse data. RESULTS: Thirty four completed
      surveys were analysed out of 49 RES (69.3%) who attended the workshop. Among
      them, there were 19 first-year, 8 second-year and 7 third-year residents.
      Following the intervention, KS increased significantly (p<0.001) with progression
      in residents' attitudes. Overall, more RES reported being comfortable with
      handling the IP, including looking up and changing the settings (p<0.001).
      CONCLUSION: There is scope for improvement in the knowledge and perceptions of
      RES regarding IPs. Educational interventions like ours are needed to familiarise
      our future physicians with IPs to allow hospitals to provide their systematic and
      safe inpatient use.

PMID- 29054931
TI  - Polycomb group RING finger proteins 3/5 activate transcription via an interaction
      with the pluripotency factor Tex10 in embryonic stem cells.
AB  - Polycomb group (PcG) proteins are epigenetic transcriptional repressors that
      orchestrate numerous developmental processes and have been implicated in the
      maintenance of embryonic stem (ES) cell state. More recent evidence suggests that
      a subset of PcG proteins engages in transcriptional activation in some cellular
      contexts, but how this property is exerted remains largely unknown. Here, we
      generated ES cells with single or combined disruption of polycomb group RING
      finger protein 3 (Pcgf3) and Pcgf5 with the CRISPR-Cas9 technique. We report that
      although these mutant cells maintained their self-renewal and colony-forming
      capacity, they displayed severe defects in mesoderm differentiation in vitro and
      in vivo Using RNA-seq to analyze transcriptional profiles of ES cells with single
      or combined Pcgf3/5 deficiencies, we found that in contrast to the canonical role
      of the related polycomb repressive complex 1 (PRC1) in gene repression, Pcgf3/5
      mainly function as transcriptional activators driving expression of many genes
      involved in mesoderm differentiation. Proteomic approaches and promoter occupancy
      analyses helped to establish an extended Pcgf3/5 interactome and identified
      several novel Pcgf3/5 interactors. These included testis-expressed 10 (Tex10),
      which may directly contribute to transcriptional activation via the
      transcriptional co-activator p300. Furthermore, Pcgf3/5 deletion in ES cells
      substantially reduced the occupancy of Tex10 and p300 at target genes. Finally,
      we demonstrated that Pcgf3/5 are essential for regulating global levels of the
      histone modifier H2AK119ub1 in ES cells. Our findings establish Pcgf3/5 as
      transcriptional activators that interact with Tex10 and p300 in ES cells and
      point to redundant activity of Pcgf3/5 in pluripotency maintenance.

PMID- 29054933
TI  - Social-media-enabled learning in emergency medicine: a case study of the growth,
      engagement and impact of a free open access medical education blog.
AB  - BACKGROUND: Clinicians are increasingly using social media for professional
      development and education. In 2012, we developed the St.Emlyn's blog, an open
      access resource dedicated to providing free education in the field of emergency
      medicine. OBJECTIVE: To describe the development and growth of this international
      emergency medicine blog. METHOD: We present a narrative description of the
      development of St.Emlyn's blog. Data on scope, impact and engagement were
      extracted from WordPress, Twitter and Google Analytics. RESULTS: The St.Emlyn's
      blog demonstrates a sustained growth in size and user engagement. Since inception
      in 2012, the site has been viewed over 1.25 million times with a linear year-on
      year growth. We have published over 500 blog posts, each of which attracts a mean
      of 2466 views (range 382-69 671). The site has been viewed in nearly every
      country in the world, although the majority (>75%) of visitors come from the USA,
      UK and Australia. SUMMARY: This case study of an emergency medicine blog
      quantifies the reach and engagement of social-media-enabled learning in emergency
      medicine.

PMID- 29054935
TI  - Familial history aggregation on acute appendicitis.
AB  - Appendectomy is the most commonly performed surgical procedure, affecting 1%-8%
      of the paediatric population, with a total 7% lifetime risk, most likely in
      adolescents and young adults.A case of familial aggregation was reported in our
      hospital in a family composed of nine siblings from which six of them (66.6%) had
      been treated of acute appendicitis, five of them in our centre.Many factors have
      been described as predisposing to appendicitis. Several studies have highlighted
      the influence of genes in the evolution of this disease and its severity,
      demonstrating a relative risk increase by three when family history is
      present.Family history of acute appendicitis is an important factor to be taken
      into consideration during the medical interview. Clinicians attempting to fine
      tune their diagnostic accuracy when patients present with acute abdominal pain
      should inquire about family history of appendicitis.

PMID- 29054934
TI  - Radiation-Induced DNA Damage in Operators Performing Endovascular Aortic Repair.
AB  - BACKGROUND: Radiation exposure during fluoroscopically guided interventions such
      as endovascular aortic repair (EVAR) is a growing concern for operators. This
      study aimed to measure DNA damage/repair markers in operators perfoming EVAR.
      METHODS: Expression of the DNA damage/repair marker, gamma-H2AX and DNA damage
      response marker, phosphorylated ataxia telangiectasia mutated (pATM), were
      quantified in circulating lymphocytes in operators during the peri-operative
      period of endovascular (infrarenal, branched, and fenestrated) and open aortic
      repair using flow cytometry. These markers were separately measured in the same
      operators but this time wearing leg lead shielding in addition to upper body
      protection and compared with those operating with unprotected legs.
      Susceptibility to radiation damage was determined by irradiating operators' blood
      in vitro. RESULTS: gamma-H2AX and pATM levels increased significantly in
      operators immediately after branched endovascular aortic repair/fenestrated
      endovascular aortic repair (P<0.0003 for both). Only pATM levels increased after
      infrarenal endovascular aortic repair (P<0.04). Expression of both markers fell
      to baseline in operators after 24 hours (P<0.003 for both). There was no change
      in gamma-H2AX or pATM expression after open repair. Leg protection abrogated
      gamma-H2AX and pATM response after branched endovascular aortic
      repair/fenestrated endovascular aortic repair. The expression of gamma-H2AX
      varied significantly when operators' blood was exposed to the same radiation dose
      in vitro (P<0.0001). CONCLUSIONS: This is the first study to detect an acute DNA
      damage response in operators performing fluoroscopically guided aortic procedures
      and highlights the protective effect of leg shielding. Defining the relationship
      between this response and cancer risk may better inform safe levels of chronic
      low-dose radiation exposure.

PMID- 29054936
TI  - A case of autosplenectomy associated with T-cell checkpoint inhibitor treatment.

PMID- 29054937
TI  - Learning from errors: unnecessary intensive care unit admissions.
AB  - An elderly man was transferred to our emergency department with reported
      ventricular tachycardia requiring intravenous amiodarone and intensive care unit
      admission. Device interrogation, the following day, revealed only frequent
      premature ventricular contractions and non-sustained ventricular tachycardia in a
      patient with a known history of these conditions. The patient underwent
      unnecessary invasive monitoring after being emergently transferred to our
      facility and admitted to the intensive care unit. Fortunately, our patient did
      not suffer any unwarranted side effects from intravenous amiodarone. This case
      reports on some negative consequences of inappropriate intensive care unit
      admissions and how they could have been avoided.

PMID- 29054938
TI  - Giant meningioma in skull radiograph.

PMID- 29054939
TI  - Result of Health Illiteracy and Cultural Stigma: Fournier's Gangrene, a
      Urological Emergency.
AB  - A 63-year-old Caucasian man presents to his regional hospital 8 days
      postinsertion of beads in his urethra, causing Fournier's gangrene of the penis
      and delayed surgical management of his gangrene. The reasons for his delay are
      cultural stigma associated with sexual practices and health illiteracy.

PMID- 29054940
TI  - Rare presentation of an old bug.
AB  - We highlight a rare presentation of Legionella infection in a 77-year-old woman
      with a clinical diagnosis of giant cell arteritis 2 months prior to presentation.
      She was started on 60 mg prednisone that was tapered to 10 mg after 4 weeks
      following her diagnosis. She presented with a 1-month progressive dyspnoea in the
      absence of any other symptoms. Her exposure history was significant only for a
      recent trip to Florida where she stayed at a hotel. Initial laboratory workup was
      significant for hyponatraemia (127 mmol/L). Workup including bronchoalveolar
      lavage (BAL) and induced sputum for gram stain, acid fast stain and bacterial
      culture were negative for Pneumocystis jirovecii pneumonia and other
      opportunistic infectious agents. However, BAL was positive for Legionella
      pneumophila via PCR that was confirmed by a positive urinary Legionella antigen.
      The patient received treatment with levofloxacin that led to full resolution of
      her symptoms.

PMID- 29054941
TI  - Unusual cause of saddle nose.

PMID- 29054942
TI  - Primary hepatic hemangioendothelioma in a patient with Budd-Chiari syndrome.
AB  - A 36-year-old woman was diagnosed with compensated cirrhosis of liver secondary
      to Budd-Chiari syndrome (BCS) and had undergone stenting of a thrombosed left
      hepatic vein. Eight months later, she presented with jaundice and right upper
      quadrant pain. CT revealed multiple focal lesions in the liver, which on biopsy
      proved to be hepatic hemangioendothelioma (HHE). Her liver disease and ascites
      progressively increased. Four months later, magnetic resonance
      cholangiopancreatography showed an advanced stage of HHE with infiltration of the
      common bile duct and vascular invasion with a blocked stent, with metastasis to
      the spleen and dorsolumbar vertebrae. We believe this is the first reported case
      of an HHE developing in the background of BCS.

PMID- 29054943
TI  - Non-infectious aortitis in an immunosuppressed renal transplant recipient with
      IgA nephropathy.
AB  - A 54-year-old woman presented with atypical chest pain, fever and malaise. She
      was immunosuppressed with three agents following a living-donor kidney transplant
      1 year previously. Her native kidney failure was secondary to biopsy-demonstrated
      crescentic IgA nephropathy, with systemic involvement. A CT pulmonary angiogram
      revealed an inflammatory cuff of soft tissue around the descending thoracic aorta
      suggesting aortitis. Inflammatory markers were elevated. Given her
      immunosuppression, the patient was screened extensively for infective causes and
      was empirically commenced on intravenous meropenem. After 72 hours of no clinical
      or serological response to antibiotic therapy, negative microbiological
      investigations and worsening inflammation on serial imaging, she was commenced on
      high-dose methylprednisolone for presumed inflammatory aortitis. Symptoms and
      inflammatory markers rapidly normalisedand the patient was discharged home on
      oral prednisolone. A clinical diagnosis of IgA-related aortitis was made. Imaging
      3 months later showed complete resolution of the aortitis.

PMID- 29054944
TI  - Anaesthesia and orphan disease: airway and anaesthetic management in Huntington's
      disease.
AB  - We present a case that highlights the issues surrounding the delivery of a safe
      general anaesthetic to a patient with Huntington's disease (HD) and bulbar
      dysfunction. In the case of a 46-year-old patient undergoing laparoscopic
      percutaneous endoscopic gastrostomy tube insertion, we discuss the rationale
      behind our chosen method and anaesthetic agents as well as airway issues specific
      to HD. In a patient whose condition would not allow for an awake fibreoptic
      intubation, we opted for a modified rapid sequence induction. Special
      considerations were made with regard to muscle relaxation given the complications
      associated with inadequate paralysis and reversal in patients with HD. The
      technique we describe may also apply to other patient categories, such as
      patients with movement disorders, bulbar dysfunction and dementia.

PMID- 29054945
TI  - Acute-onset diplopia in a case of nephrotic syndrome.

PMID- 29054946
TI  - Management challenges of late presentation Dacron patch infection after carotid
      endarterectomy.
AB  - An 83-year-old man presented 4 years after right carotid endarterectomy (CEA)
      with an infection of his prosthetic Dacron patch. Initial scans (CT angiogram and
      whole body labelled white cell scan) were clear with no infection or collection
      noted. Systemically, the patient presented well with no recorded fevers. With an
      occluded left internal carotid artery and severely stenosed vertebral arteries,
      surgery presented a high risk of major stroke due to the lack collateral supply
      and this was discussed extensively. The patient subsequently declined surgical
      management, and he was monitored closely on an outpatient basis. He presented
      again a year later with ongoing haemoserous ooze from the CEA site. Subsequently
      a two-stage procedure was performed, where initially a stent was inserted,
      followed by patch excision and debridement. A muscle flap was then mobilised over
      the opening. This new approach to carotid patch infections should gain traction
      over time as a safer alternative for high-risk patients.

PMID- 29054947
TI  - A case of tuberculous gumma: there is more to it than meets the eye.
AB  - We present a case of a young girl who presented with multiple cutaneous abscesses
      over 2 years at different sites. She had no constitutional symptoms or history of
      tuberculosis. On investigation, she was found to have rifampicin-sensitive
      tuberculosis presenting as tubercular gumma, a rare form of cutaneous
      tuberculosis which occurs due to haematogenous spread of the bacilli. She had
      disseminated disease involving the spinal column with associated psoas abscess. A
      thorough evaluation was done for immune-deficiency workup but was all negative.
      She was given antitubercular therapy and showed a good response to therapy at a
      follow-up of 1 month.

PMID- 29054948
TI  - Gentamicin-vancomycin-colistin local antibiotherapy in a cement spacer in a 54
      year-old haemophilic patient with relapsing plurimicrobial severe prosthetic
      joint infection.

PMID- 29054949
TI  - Metachronous solitary plasmacytoma.
AB  - Solitary plasmacytoma is a rare disorder comprising 5%-10% of all plasma cell
      neoplasms. Progression to multiple myeloma is the most common pattern of relapse.
      Appearance of new lesions without any systemic disease is the most unusual
      pattern of relapse seen in <2% cases. We present a case of a 46-year-old female
      who presented with features of third and seventh cranial nerve palsy, diagnosed
      with solitary plasmacytoma, with no evidence of any systemic disease. As per
      standard recommendations, the patient received radiotherapy to the local site.
      The patient developed relapse twice, at three sites, during the follow-up period.
      Investigations revealed no evidence of any systemic disease. In view of repeat
      relapses, the patient was started on immune modulatory agent. Two and half years
      after the last radiotherapy, the patient is symptom free with no evidence of any
      new lesion.

PMID- 29054950
TI  - Amyand's hernia detected incidentally in two patients.
AB  - The appendix is rarely present inside the inguinal hernia sac. The risk of
      appendicitis increases in these patients since the blood supply to the appendix
      can be impaired. The condition is frequently asymptomatic, and even if
      symptomatic it gives rise to non-specific symptoms. There is no specific
      laboratory finding. Diagnosis is frequently made with radiological imaging. We
      report two cases diagnosed as Amyand's hernia with CT.

PMID- 29054951
TI  - Community-acquired Pseudomonas aeruginosa meningitis.
AB  - Gram-negative bacilli such as Pseudomonas aeruginosa are a rare cause of
      meningitis. Patients developing P. aeruginosa meningitis most commonly have a
      history of neurosurgical procedures. We report a patient who presented with
      community-acquired chronic meningitis secondary to P. aeruginosa, related to
      surgery for otosclerosis 5 years previously.

PMID- 29054952
TI  - Re-correction osteotomy with osteophyte graft for correction loss with non-union
      after high tibial osteotomy.
AB  - A 68-year-old man with right knee varus osteoarthritis was treated by lateral
      closed-wedge high tibial osteotomy. A correction loss with non-union occurred 6
      months after surgery and a re-correction osteotomy was performed. Removing the
      proximal screws of the lateral plate, a medial opening-wedge re-osteotomy was
      performed. Arthroscopically harvested osteophytes were used to fill the gap after
      opening. An additional medial locking plate was installed on the medial side.
      Finally, the proximal lateral screws were reinserted and locked again. Mature
      trabecular continuity was obtained in the gap by 6 months, and there was no varus
      deformity 4 years after re-correction. Re-correction osteotomy could be a viable
      treatment when lateral compartment osteoarthritis has not progressed and good
      range of motion still exists. Osteophyte grafting may be an effective option not
      only to avoid iliac bone grafting but also to promote bone healing in re
      osteotomy.

PMID- 29054953
TI  - Vancomycin-associated drug reaction with eosinophilia and systemic symptoms
      (DRESS) syndrome: masquerading under the guise of sepsis.
AB  - A patient presented with what appeared to be severe urosepsis. After admission
      and antibiotic administration, a newly developed rash and subsequent facial
      swelling appeared to be a reaction to penicillin class antibiotics. However,
      despite changing class of therapy with continued antimicrobial coverage, end
      organ damage continued, the rash worsened and facial oedema developed. Drug
      reaction with eosinophilia and systemic symptoms was ultimately diagnosed and was
      consistent with clinical and histopathological findings, as well as meeting all
      criteria for scoring systems. The patient was started on intravenous
      methylprednisolone 125 mg per 8 hours with rapid improvement of rash, swelling
      and end organ damage. Initial challenge to decrease dose failed, but the patient
      was ultimately able to be discharged on an extended taper.

PMID- 29054954
TI  - Cerebellar ataxia and neuropathy as presenting features of hepatitis-B related
      cirrhosis and portal hypertension.
AB  - Adult onset cerebellar dysfunction with neuropathy is a commonly encountered
      condition and is usually due to genetic causes such as spinocerebellar ataxia,
      gluten ataxia, alcohol related, toxic, degenerative, immune mediated,
      paraneoplastic causes and so on. Ataxia and neuropathy as presenting features of
      hepatitis-B related liver disease are very rare and have not been reported so
      far.

PMID- 29054955
TI  - Trapped ipsilateral lateral ventricle: a delayed complication of hemispherotomy
      for Rasmussen's encephalitis.
AB  - Hemispherotomy is the currently preferred surgical treatment option for
      refractory unihemispheric epilepsies. The incidence of hydrocephalus is greatly
      reduced in this disconnective procedure when compared with the resective
      procedure of anatomical hemispherectomy. We describe the occurrence of
      ipsilateral trapped lateral ventricle months after hemispherotomy for Rasmussen's
      encephalitis. There is enough evidence to suggest that this rare and interesting
      complication is due to the local inflammatory changes associated with the
      surgical trauma.

PMID- 29054956
TI  - Indirect carotid cavernous fistula mimicking ocular myasthenia.
AB  - 71-year-old woman with progressive left-sided, monocular diplopia and ptosis. Her
      symptoms mimicked ocular myasthenia, but she had an indirect carotid cavernous
      fistula (CCF). She was diagnosed with monocular myasthenia gravis (negative
      acetylcholinesterase antibody) after a positive ice test and started on Mestinon
      and underwent a thymectomy complicated by a brachial plexus injury. Months later,
      she developed left-sided proptosis and ocular bruit. She was urgently referred to
      neuro-interventional surgery and was diagnosed with an indirect high-flow left
      CCF, which was treated with Onyx liquid and platinum coil embolisation. Mestinon
      was discontinued. Her ophthalmic symptoms resolved. However, she was left with a
      residual left arm and hand hemiparesis and dysmetria secondary to a brachial
      plexus injury. Indirect CCF usually can present with subtle and progressive
      symptoms leading to delayed diagnosis or misdiagnosis. It is important for
      ophthalmologists to consider this differential in a patient with progressive
      ocular symptoms.

PMID- 29054957
TI  - Memory of World War II with loud atypical friction rub due to pulmonary
      asbestosis.

PMID- 29054958
TI  - Bone and muscular viability assessment before amputation: usefulness of bone scan
      and 99mTc sestamibi dual-phase scintigraphy.

PMID- 29054959
TI  - Honeycomb and necklace signs in liver abscesses secondary to melioidosis.
AB  - Melioidosis is endemic in Southeast Asia and tropical Australia with varying
      clinical features from benign skin lesions to fatal septicaemia. Imaging plays an
      important role in evaluation of the melioid liver abscesses. A 45-year-old man
      with underlying diabetes presented with fever and lethargy for 2 weeks and
      abdominal pain for 2 days. His liver was enlarged on examination. Blood
      investigations revealed mild leucocytosis and raised liver enzymes. Ultrasound
      showed multiple multiloculated hypoechoic lesions throughout the liver and
      spleen. CT of abdomen confirmed that some liver lesions were made up of
      asymmetric locules of varying sizes (honeycomb sign), while others had hypodense
      centre with small symmetric peripheral locules in radial fashion (necklace sign).
      Blood culture was positive for Burkholderia pseudomallei He was subsequently
      treated with ceftazidime for a month followed by oral trimethoprim
      sulfamethoxazole for 3 months. Follow-up CT of abdomen a month after diagnosis
      and treatment showed resolving hepatic and splenic lesions.

PMID- 29054960
TI  - A simple turnover technique to harvest skin graft from the avulsed skin.

PMID- 29054961
TI  - Cytoplasmic transport and nuclear import of plasmid DNA.
AB  - Productive transfection and gene transfer require not simply the entry of DNA
      into cells and subsequent transcription from an appropriate promoter, but also a
      number of intracellular events that allow the DNA to move from the extracellular
      surface of the cell into and through the cytoplasm, and ultimately across the
      nuclear envelope and into the nucleus before any transcription can initiate.
      Immediately upon entry into the cytoplasm, naked DNA, either delivered through
      physical techniques or after disassembly of DNA-carrier complexes, associates
      with a large number of cellular proteins that mediate subsequent interactions
      with the microtubule network for movement toward the microtubule organizing
      center and the nuclear envelope. Plasmids then enter the nucleus either upon the
      mitotic disassembly of the nuclear envelope or through nuclear pore complexes in
      the absence of cell division, using a different set of proteins. This review will
      discuss our current understanding of these pathways used by naked DNA during the
      transfection process. While much has been elucidated on these processes, much
      remains to be discerned, but with the development of a number of model systems
      and approaches, great progress is being made.

PMID- 29054962
TI  - Expanded alleles of the FMR1 gene are related to unexplained recurrent
      miscarriages.
AB  - Up to 50% of recurrent miscarriage cases in women occur without an underlying
      etiology. In the current prospective case-control study, we determined the impact
      of CGG trinucleotide expansions of the fragile-X mental retardation 1 (FMR1) gene
      in 49 women with unexplained recurrent miscarriages. Case group consisted of
      women with two or more unexplained consecutive miscarriages. Blood samples were
      obtained and checked for the presence of expanded alleles of the FMR1 gene using
      PCR. Patients harboring the expanded allele, with a threshold set to 40 repeats,
      were further evaluated by sequencing. The number of abortions each woman had, was
      not associated with her respective CGG repeat number (P=0.255). The repeat sizes
      of CGG expansion in the FMR1 gene were significantly different in the two
      population groups (P=0.027). All the positive cases involved intermediate zone
      carriers. Hence, the CGG expanded allele of the FMR1 gene might be associated
      with unexplained multiple miscarriages; whether such an association is
      coincidental or causal can be confirmed by future studies using a larger patient
      cohort.

PMID- 29054963
TI  - Interleukin-12-mediated expression of matrix metalloproteinases in human
      periodontal ligament fibroblasts involves in NF-kappaB activation.
AB  - Interleukin-12 (IL-12) is a proinflammatory cytokine, and its increased level
      correlates with the severity of periodontitis. However, its role in the
      pathogenesis of tooth periapical lesions is controversial and has not been
      completely clarified. The present study aimed to investigate whether IL-12
      affects the expression of matrix metalloproteinases (MMPs) and tissue inhibitors
      of metalloproteinases (TIMPs) in human periodontal ligament fibroblasts (hPDLFs).
      After treatment with IL-12 for different times, real-time PCR and Western
      blotting were used to determine the mRNA and protein levels of MMP-1, MMP-2, MMP
      3, MMP-9, MMP-13, TIMP-1, and TIMP-2, respectively. ELISA was applied to measure
      MMPs and TIMPs secretion production. The results indicated that IL-12
      significantly increased the mRNA and protein expression levels of MMP-1, MMP-3,
      and MMP-13, but down-regulated MMP-2 and MMP-9 mRNA and protein expression in the
      hPDLFs. Furthermore, IL-12 (10 ng/ml) enhanced the secreted protein production of
      MMP-1, MMP-3, and MMP-13, and conversely lowered MMP-2 and MMP-9 secretion
      levels. However, IL-12 treatment did not exert a significant effect on the mRNA
      and protein levels of TIMP-1 and TIMP-2 and their secreted production.
      Additionally, IL-12 increased the phosphorylated levels of IkappaBalpha and
      nuclear factor-kappaB P65 (NF-kappaB P65), and promoted NF-kappaB P65 subunit
      nuclear translocation. Pretreatment with NF-kappaB inhibitor not only attenuated
      IL-12-induced IkappaBalpha and NF-kappaB P65 phosphorylation and inhibited NF
      kappaB P65 subunit into nucleus, but also antagonized IL-12-mediated MMP-1, MMP
      2, MMP-3, MMP-9, and MMP-13 expression in the hPDLFs. These findings indicate
      that NF-kappaB-dependent activation is possibly indispensable for IL-12-mediated
      MMP expression in hPDLFs.

PMID- 29054964
TI  - Gene expression profiling of the Notch-AhR-IL22 axis at homeostasis and in
      response to tissue injury.
AB  - Notch and interleukin-22 (IL-22) signaling are known to regulate tissue
      homeostasis and respond to injury in humans and mice, and the induction of
      endogenous aryl hydrocarbon receptor (Ahr) ligands through Notch links the two
      pathways in a hierarchical fashion. However in adults, the species-, organ- and
      injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown.
      We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2,
      JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TNF-alpha ADAM metalloprotease
      converting enzyme (TACE), PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1,
      HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and
      STAT3 under homeostatic conditions in ten mature murine and human organs.
      Additionally, the expression of these genes was assessed in murine models of
      acute sterile inflammation and progressive fibrosis. We show that there are organ
      specific gene expression profiles of the Notch-AhR-IL22 axis in humans and mice.
      Although there is an overall interspecies congruency, specific differences
      between human and murine expression signatures do exist. In murine tissues with
      AHR/ARNT expression CYP1A1 and IL-22 were correlated with HES5 and HEYL
      expression, while in human tissues no such correlation was found. Notch and AhR
      signaling are involved in renal inflammation and fibrosis with specific gene
      expression changes in each model. Despite the presence of all Notch pathway
      molecules in the kidney and a model-specific induction of Notch ligands, IL-22
      was only up-regulated in acute inflammation, but rapidly down-regulated during
      regeneration. This implies that for targeting injury responses, e.g. via IL-22,
      species-specific differences, injury type and time points have to be considered.

PMID- 29054965
TI  - Adenovirus-mediated artificial miRNA targetting fibrinogen-like protein 2
      attenuates the severity of acute pancreatitis in mice.
AB  - Severe acute pancreatitis (SAP) remains to be challenging for its unpredictable
      inflammatory progression from acute pancreatitis to SAP. Apoptosis is an
      important pathology of SAP. Fibrinogen-like protein 2 (FGL2) has been reported to
      be involved in apoptosis. The present study aimed to explore the therapeutic
      effect of an adenovirus-mediated artificial miRNA targetting FGL2 (Ad-FGL2-miRNA)
      in taurocholate-induced murine pancreatitis models. Sodium taurocholate was
      retrogradely injected into the biliopancreatic ducts of the C57/BL mice to induce
      SAP. FGL2 expression was measured with reverse transcription-PCR, Western
      blotting, and immunohistochemical staining. ELISA was used to detect the activity
      of amylase and the concentrations of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1beta (IL-1beta). In addition, the mRNA levels of TNF-alpha and IL
      1beta were also detected. Finally, apoptosis was assessed by terminal
      deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL)
      method and Western blotting. Ad-FGL2-miRNA significantly suppressed FGL2
      expression and alleviated pancreatic injury. Also, Ad-FGL2-miRNA markedly
      inhibited a post-SAP increase in the activation of TNF-alpha and IL-1beta.
      Finally, pretreatment with Ad-FGL2-miRNA ameliorated apoptosis at the early stage
      of SAP by modulating cleaved caspase-3 and therefore played a protective role.
      These results indicated that FGL2 might be a promising target for attenuating the
      severity of SAP and adenovirus-mediated artificial miRNAs targetting FGL2
      represented a potential therapeutic approach for the treatment of SAP.

PMID- 29054966
TI  - Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small
      cell lung cancer.
AB  - A recent study indicated that high Wnt5a expression is associated with poor
      prognosis in non-small-cell lung cancer (NSCLC) patients; however, the underlying
      mechanism was not clear yet. Immunohistochemistry and Western blotting were
      performed to examine the protein expression level in NSCLC tissues and cell
      lines. The role of Wnt5a in clone formation, invasiveness, migration, and
      epithelial-to-mesenchymal transition (EMT) of NSCLC cells was studied. Luciferase
      reporter assay was used to evaluate the Tcf/Lef transcriptional activity. For
      assessing the effects of Wnt5a on tumor growth and metastasis in vivo, A549 cells
      transfected with sh-Wnt5a were subcutaneously or orthotopically injected into
      nude mice. In NSCLC tissues, higher expression levels of Wnt5a and ROR2 were
      found, beta-Catenin was expressed exceptionally, and EMT was prompted. Wnt5a
      overexpression increased clone formation, migration, and invasion, as well as
      prompted EMT of NSCLC cell in vitro, whereas Wnt5a knockdown showed the
      absolutely reversed results. Wnt5a overexpression enhanced the Tcf/Lef
      transcriptional activity and elevated the nuclear beta-catenin level in NSCLC
      cells, without altering the ROR2 expression. We also demonstrated that si-beta
      catenin antagonized Wnt5a overexpression nduced EMT and invasiveness. Besides, in
      vivo experiment showed that sh-Wnt5a significantly increased tumor volume and
      tumor weight, and prompted EMT in A549 tumor-bearing mice as compared with the
      control. No metastasis was found in the liver tissue after sh-Wnt5a-transfected
      cells were orthotopically injected into nude mice as compared with the control.
      In conclusion, Wnt5a promotes EMT and metastasis in NSCLC, which is involved in
      the activation of beta-catenin-dependent canonical Wnt signaling.

PMID- 29054967
TI  - Prediction of cytochrome P450-mediated drug clearance in humans based on the
      measured activities of selected CYPs.
AB  - Determining drug-metabolizing enzyme activities on an individual basis is an
      important component of personalized medicine, and cytochrome P450 enzymes (CYPs)
      play a principal role in hepatic drug metabolism. Herein, a simple method for
      predicting the major CYP-mediated drug clearance in vitro and in vivo is
      presented. Ten CYP-mediated drug metabolic activities in human liver microsomes
      (HLMs) from 105 normal liver samples were determined. The descriptive models for
      predicting the activities of these CYPs in HLMs were developed solely on the
      basis of the measured activities of a smaller number of more readily assayed
      CYPs. The descriptive models then were combined with the Conventional Bias
      Corrected in vitro-in vivo extrapolation method to extrapolate drug clearance in
      vivo. The Vmax, Km, and CLint of six CYPs (CYP2A6, 2C8, 2D6, 2E1, and 3A4/5)
      could be predicted by measuring the activities of four CYPs (CYP1A2, 2B6, 2C9,
      and 2C19) in HLMs. Based on the predicted CLint, the values of CYP2A6-, 2C8-, 2D6
      , 2E1-, and 3A4/5-mediated drug clearance in vivo were extrapolated and found
      that the values for all five drugs were close to the observed clearance in vivo
      The percentage of extrapolated values of clearance in vivo which fell within 2
      fold of the observed clearance ranged from 75.2% to 98.1%. These findings suggest
      that measuring the activity of CYP1A2, 2B6, 2C9, and 2C19 allowed us to
      accurately predict CYP2A6-, 2C8-, 2D6-, 2E1-, and 3A4/5-mediated activities in
      vitro and in vivo and may possibly be helpful for the assessment of an
      individual's drug metabolic profile.

PMID- 29054969
TI  - alpha-Mangostin protects against high-glucose induced apoptosis of human
      umbilical vein endothelial cells.
AB  - Diabetic vascular complications result from high-glucose induced vascular
      endothelial cell dysfunction. There is an emerging need for novel drugs with
      vascular endothelial cell protective effects for the treatment of diabetic
      vascular complications. The present study aimed to investigate the protective
      effect of alpha-mangostin against high-glucose induced apoptosis of cultured
      human umbilical vein endothelial cells (HUVECs). HUVECs were treated with glucose
      to induce apoptosis. The expression of the apoptosis-related proteins, Bcl-2,
      Bax, and cleaved caspase-3, were detected by Western blotting. Ceramide
      concentration and acid sphingomyelinase (ASM) activity were assayed by HPLC. The
      cell apoptosis rate was detected by flow cytometry after staining with annexin
      V/propidium iodide (PI). Compared with HUVECs cultured in 5 mM glucose, cells
      cultured in 30 mM glucose exhibited a higher apoptosis rate, up-regulation of
      cleaved caspase-3 and Bax (proapoptotic proteins), down-regulation of Bcl-2 (anti
      apoptotic protein), increased ceramide concentration, and enhanced ASM activity
      (all P<0.05). alpha-Mangostin (15 uM) significantly attenuated the high-glucose
      induced increase in apoptosis rate (8.64 +/- 2.16 compared with 19.6 +/- 3.54%),
      up-regulation of cleaved caspase-3 and Bax, down-regulation of Bcl-2, elevation
      of ceramide level, and enhancement of ASM activity (all P<0.05). The effects of
      desipramine were similar to those of alpha-mangostin. The protective effect of
      alpha-mangostin on high-glucose induced apoptotic damage may be mediated by an
      inhibition of ASM and thus a decreased level of ceramide.

PMID- 29054968
TI  - Pivotal neuroinflammatory and therapeutic role of high mobility group box 1 in
      ischemic stroke.
AB  - Stroke is a major cause of mortality and disability worldwide. Stroke is a
      frequent and severe neurovascular disorder. The main cause of stroke is
      atherosclerosis, and the most common risk factor for atherosclerosis is
      hypertension. Therefore, prevention and treatment of stroke are crucial issues in
      humans. High mobility group box 1 (HMGB1) is non-histone nuclear protein that is
      currently one of the crucial proinflammatory alarmins in ischemic stroke (IS). It
      is instantly released from necrotic cells in the ischemic core and activates an
      early inflammatory response. HMGB1 may signal via its putative receptors, such as
      receptor for advanced glycation end products (RAGE), toll-like receptors (TLRs)
      as well as matrix metalloproteinase (MMP) enzymes during IS. These receptors are
      expressed in brain cells. Additionally, brain-released HMGB1 can be redox
      modified in the circulation and activate peripheral immune cells. The role of
      HMGB1 may be more complex. HMGB1 possesses beneficial actions, such as
      endothelial activation, enhancement of neurite outgrowth, and neuronal survival.
      HMGB1 may also provide a novel link for brain-immune communication leading to
      post-stroke immunomodulation. Therefore, HMGB1 is new promising therapeutic
      intervention aimed at promoting neurovascular repair and remodeling after stroke.
      In this review, we look at the mechanisms of secretion of HMGB1, the role of
      receptors, MMP enzymes, hypoglycemia, atherosclerosis, edema, angiogenesis as
      well as neuroimmunological reactions and post-ischemic brain recovery in IS. We
      also outline therapeutic roles of HMGB1 in IS.

PMID- 29054970
TI  - miR-19a protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via
      PTEN/PI3K/p-Akt pathway.
AB  - miRNAs have been implicated in processing of cardiac hypoxia/reoxygenation (H/R)
      induced injury. Recent studies demonstrated that miR-19a might provide a
      potential cardioprotective effect on myocardial disease. However, the effect of
      miR-19a in regulating myocardial ischemic injury has not been previously
      addressed. The present study was to investigate the effect of miR-19a on
      myocardial ischemic injury and identified the potential molecular mechanisms
      involved. Using the H/R model of rat cardiomyocytes H9C2 in vitro, we found that
      miR-19a was in low expression in H9C2 cells after H/R treatment and H/R
      dramatically decreased cardiomyocyte viability, and increased lactate
      dehydrogenase (LDH) release and cardiomyocyte apoptosis, which were attenuated by
      co-transfection with miR-19a mimic. Dual-luciferase reporter assay and Western
      blotting assay revealed that PTEN was a direct target gene of miR-19a, and miR
      19a suppressed the expression of PTEN via binding to its 3'-UTR. We further
      identified that overexpression of miR-19a inhibited the expression of PTEN at the
      mRNA and protein levels. Moreover, PTEN was highly expressed in H/R H9C2 cells
      and the apoptosis induced by H/R was associated with the increase in PTEN
      expression. Importantly, miR-19a mimic significantly increased p-Akt levels under
      H/R. In conclusion, our findings indicate that miR-19a could protect against H/R
      induced cardiomyocyte apoptosis by inhibiting PTEN /PI3K/p-Akt signaling pathway.

PMID- 29054971
TI  - A novel G-quadruplex motif in the Human MET promoter region.
AB  - It is known that the guanine-rich strands in proto-oncogene promoters can fold
      into G-quadruplex structures to regulate gene expression. An intramolecular
      parallel G-quadruplex has been identified in MET promoter. It acts as a repressor
      in regulating MET expression. However, the full guanine-rich region in MET
      promoter forms a hybrid parallel/antiparallel G-quadruplex structure under
      physiological conditions, which means there are some antiparallel and hybrid
      parallel/antiparallel G-quadruplex structures in this region. In the present
      study, our data indicate that g3-5 truncation adopts an intramolecular hybrid
      parallel/antiparallel G-quadruplex under physiological conditions in vitro The g3
      5 G-quadruplex structure significantly stops polymerization by Klenow fragment in
      K+ buffer. Furthermore, the results of circular dichroism (CD) spectra and
      polymerase stop assay directly demonstrate that the G-quadruplex structure in g3
      5 fragment can be stabilized by the G-quadruplex ligand TMPyP4 (5,10,15,20-tetra
      (N-methyl-4-pyridyl) porphine). But the dual luciferase assay indicates TMPyP4
      has no effect on the formation of g3-5 G-quadruplex in HepG2 cells. The findings
      in the present study will enrich our understanding of the G-quadruplex formation
      in proto-oncogene promoters and the mechanisms of gene expression regulation.

PMID- 29054973
TI  - Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve
      responses during dynamic skeletal muscle stretch in decerebrate rats.
AB  - Mechanical and metabolic signals arising during skeletal muscle contraction
      reflexly increase sympathetic nerve activity and blood pressure (i.e., the
      exercise pressor reflex). In a rat model of simulated peripheral artery disease
      in which a femoral artery is chronically (~72 h) ligated, the mechanically
      sensitive component of the exercise pressor reflex during 1-Hz dynamic
      contraction is exaggerated compared with that found in normal rats. Whether this
      is due to an enhanced acute sensitization of mechanoreceptors by metabolites
      produced during contraction or involves a chronic sensitization of
      mechanoreceptors is unknown. To investigate this issue, in decerebrate,
      unanesthetized rats, we tested the hypothesis that the increases in mean arterial
      blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch
      are larger when evoked from a previously "ligated" hindlimb compared with those
      evoked from the contralateral "freely perfused" hindlimb. Dynamic stretch
      provided a mechanical stimulus in the absence of contraction-induced metabolite
      production that closely replicated the pattern of the mechanical stimulus present
      during dynamic contraction. We found that the increases in mean arterial blood
      pressure (freely perfused: 14 +/- 1 and ligated: 23 +/- 3 mmHg, P = 0.02) and
      renal sympathetic nerve activity were significantly greater during dynamic
      stretch of the ligated hindlimb compared with the increases during dynamic
      stretch of the freely perfused hindlimb. These findings suggest that the
      exaggerated mechanically sensitive component of the exercise pressor reflex found
      during dynamic muscle contraction in this rat model of simulated peripheral
      artery disease involves a chronic sensitizing effect of ligation on muscle
      mechanoreceptors and cannot be attributed solely to acute contraction-induced
      metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and
      sympathetic nerve responses during dynamic stretch were exaggerated in rats with
      a ligated femoral artery (a model of peripheral artery disease). Our findings
      provide mechanistic insights into the exaggerated exercise pressor reflex in this
      model and may have important implications for peripheral artery disease patients.

PMID- 29054972
TI  - Endothelial function is impaired in the cutaneous microcirculation of adults with
      psoriasis through reductions in nitric oxide-dependent vasodilation.
AB  - Psoriasis is an independent risk factor for cardiovascular disease; however, the
      underlying mechanisms are not fully understood. Deficits in conduit arterial
      function are evident in patients with psoriasis, but potential impairments in
      microcirculatory endothelial function remain unclear. We hypothesized that
      cutaneous microvascular dysfunction would be detectable in otherwise healthy
      individuals with psoriasis. Two intradermal microdialysis fibers were placed in
      (nonlesional) forearm skin of nine patients (3 men and 6 women, 39 +/- 5 yr) with
      moderate (16 +/- 2% of body surface area) plaque psoriasis and nine healthy
      (nonpsoriatic) control subjects (3 men and 6 women, 38 +/- 5 yr) for local
      delivery of 1) lactated Ringer solution (control) and 2) 10 mM l-ascorbate (a
      nonspecific antioxidant). An index of skin blood flow was measured using laser
      Doppler flowmetry during local heating (42 degrees C). Nitric oxide (NO)
      dependent vasodilation was directly quantified after perfusion of the nonspecific
      NO synthase inhibitor NG-nitro-l-arginine methyl ester (15 mM). A third fiber was
      perfused with increasing concentrations (10-10 - 10-2 M) of norepinephrine to
      elicit adrenoreceptor-mediated cutaneous vasoconstriction. NO-dependent
      vasodilation was attenuated in patients with psoriasis (57 +/- 5% and 39 +/- 7%
      maximum cutaneous vascular conductance in control subjects and adults with
      psoriasis, respectively, P < 0.01). l-Ascorbate did not improve NO-dependent
      vasodilation ( P > 0.05). There was no group difference in maximal
      vasoconstriction or microvascular sensitivity to norepinephrine ( P > 0.05).
      These data suggest that NO bioavailability is reduced in otherwise healthy
      individuals with psoriasis, which contributes to systemic microvascular
      dysfunction. NEW & NOTEWORTHY In adults with psoriasis, reduced nitric oxide
      bioavailability mediates impaired endothelium-dependent vasodilation, independent
      of increases in oxidative stress. Furthermore, the degree of psoriatic
      symptomology is directly related to greater reductions in nitric oxide-dependent
      vasodilation.

PMID- 29054974
TI  - Laryngeal closure impedes non-invasive ventilation at birth.
AB  - BACKGROUND: Non-invasive ventilation is sometimes unable to provide the
      respiratory needs of very premature infants in the delivery room. While airway
      obstruction is thought to be the main problem, the site of obstruction is
      unknown. We investigated whether closure of the larynx and epiglottis is a major
      site of airway obstruction. METHODS: We used phase contrast X-ray imaging to
      visualise laryngeal function in spontaneously breathing premature rabbits
      immediately after birth and at approximately 1 hour after birth. Non-invasive
      respiratory support was applied via a facemask and images were analysed to
      determine the percentage of the time the glottis and the epiglottis were open.
      HYPOTHESIS: Immediately after birth, the larynx is predominantly closed, only
      opening briefly during a breath, making non-invasive intermittent positive
      pressure ventilation (iPPV) ineffective, whereas after lung aeration, the larynx
      is predominantly open allowing non-invasive iPPV to ventilate the lung. RESULTS:
      The larynx and epiglottis were predominantly closed (open 25.5%+/-1.1% and
      17.1%+/-1.6% of the time, respectively) in pups with unaerated lungs and unstable
      breathing patterns immediately after birth. In contrast, the larynx and the
      epiglottis were mostly open (90.5%+/-1.9% and 72.3%+/-2.3% of the time,
      respectively) in pups with aerated lungs and stable breathing patterns
      irrespective of time after birth. CONCLUSION: Laryngeal closure impedes non
      invasive iPPV at birth and may reduce the effectiveness of non-invasive
      respiratory support in premature infants immediately after birth.

PMID- 29054975
TI  - Nuclear transport of the Neurospora crassa NIT-2 transcription factor is mediated
      by importin-alpha.
AB  - The Neurospora crassa NIT-2 transcription factor belongs to the GATA
      transcription factor family and plays a fundamental role in the regulation of
      nitrogen metabolism. Because NIT-2 acts by accessing DNA inside the nucleus,
      understanding the nuclear import process of NIT-2 is necessary to characterize
      its function. Thus, in the present study, NIT-2 nuclear transport was
      investigated using a combination of biochemical, cellular, and biophysical
      methods. A complemented strain that produced an sfGFP-NIT-2 fusion protein was
      constructed, and nuclear localization assessments were made under conditions that
      favored protein translocation to the nucleus. Nuclear translocation was also
      investigated using HeLa cells, which showed that the putative NIT-2 nuclear
      localization sequence (NLS; 915TISSKRQRRHSKS927) was recognized by importin-alpha
      and that subsequent transport occurred via the classical import pathway. The
      interaction between the N. crassa importin-alpha (NcImpalpha) and the NIT-2 NLS
      was quantified with calorimetric assays, leading to the observation that the
      peptide bound to two sites with different affinities, which is typical of a
      monopartite NLS sequence. The crystal structure of the NcImpalpha/NIT-2 NLS
      complex was solved and revealed that the NIT-2 peptide binds to NcImpalpha with
      the major NLS-binding site playing a primary role. This result contrasts other
      recent studies that suggested a major role for the minor NLS-binding site in
      importin-alpha from the alpha2 family, indicating that both sites can be used for
      different cargo proteins according to specific metabolic requirements.

PMID- 29054976
TI  - Regulation of insulin-like growth factor receptors by Ubiquilin1.
AB  - Insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase that
      mediates growth, proliferation and survival. Dysregulation of IGF pathway
      contributes to the initiation, progression and metastasis of cancer and is also
      involved in diseases of glucose metabolism, such as diabetes. We have identified
      Ubiquilin1 (UBQLN1) as a novel interaction partner of IGF1R, IGF2R and insulin
      receptor (INSR). UBQLN family of proteins have been studied primarily in the
      context of protein quality control and in the field of neurodegenerative
      disorders. Our laboratory discovered a link between UBQLN1 function and
      tumorigenesis, such that UBQLN1 is lost and underexpressed in 50% of human lung
      adenocarcinoma cases. We demonstrate here that UBQLN1 regulates the expression
      and activity of IGF1R. Following loss of UBQLN1 in lung adenocarcinoma cells,
      there is accelerated loss of IGF1R. Despite decreased levels of total receptors,
      the ratio of active : total receptors is higher in cells that lack UBQLN1. UBQLN1
      also regulates INSR and IGF2R post-stimulation with ligand. We conclude that
      UBQLN1 is essential for normal regulation of IGF receptors. UBQLN-1-deficient
      cells demonstrate increased cell viability compared with control when serum
      starved and stimulation of IGF pathway in these cells increased their migratory
      potential by 3-fold. As the IGF pathway is involved in processes of normal
      growth, development, metabolism and cancer progression, understanding its
      regulation by Ubiquilin1 can be of tremendous value to many disciplines.

PMID- 29054977
TI  - Synthesis and degradation of cAMP in Giardia lamblia: possible role and
      characterization of a nucleotidyl cyclase with a single cyclase homology domain.
AB  - Despite its importance in the regulation of growth and differentiation processes
      of a variety of organisms, the mechanism of synthesis and degradation of cAMP
      (cyclic AMP) has not yet been described in Giardia lamblia In this work, we
      measured significant quantities of cAMP in trophozoites of G. lamblia incubated
      in vitro and later detected how it increases during the first hours of
      encystation, and how it then returns to basal levels at 24 h. Through an analysis
      of the genome of G. lamblia, we found sequences of three putative enzymes - one
      phosphodiesterase (gPDE) and two nucleotidyl cyclases (gNC1 and gNC2) - that
      should be responsible for the regulation of cAMP in G. lamblia Later, an RT-PCR
      assay confirmed that these three genes are expressed in trophozoites. The
      bioinformatic analysis indicated that gPDE is a transmembrane protein of 154 kDa,
      with a single catalytic domain in the C-terminal end; gNC1 is predicted to be a
      transmembrane protein of 74 kDa, with only one class III cyclase homology domain
      (CHD) at the C-terminal end; and gNC2 should be a transmembrane protein of 246
      kDa, with two class III CHDs. Finally, we cloned and enriched the catalytic
      domain of gNC1 (gNC1cd) from bacteria. After that, we confirmed that gNC1cd has
      adenylyl cyclase (AC) activity. This enzymatic activity depends on the presence
      of Mn2+ and Ca2+, but no significant activity was displayed in the presence of
      Mg2+ Additionally, the AC activity of gNC1cd is competitively inhibited with GTP,
      so it is highly possible that gNC1 has guanylyl cyclase activity as well.

PMID- 29054979
TI  - How much is too much medicine?

PMID- 29054980
TI  - One-Year Language Outcomes in Toddlers With Language Delays: An RCT Follow-up.
AB  - OBJECTIVES: The current study is a 1-year follow-up analysis of data from a
      randomized controlled trial of Enhanced Milieu Teaching (EMT) for toddlers with
      language delays. Outcomes and predictors of child language and parent
      intervention implementation were examined 6 and 12 months after the end of the
      intervention. METHODS: Toddlers with language delays were recruited from the
      community, and 97 toddlers and parents were randomly assigned to receive usual
      community treatments or a 3-month EMT intervention with parent training. Multiple
      regression analyses were used to estimate the differences between groups at the 6
      and 12-month follow-up periods. A subgroup of participants with receptive and
      expressive language delays was used in a post hoc moderator analysis of treatment
      outcomes. RESULTS: Children in the treatment arm did not differ from children in
      the control arm at 6- and 12-month follow-ups. However, post hoc analyses
      revealed that children with receptive-expressive language delays were
      persistently delayed relative to normative performance throughout the follow-up
      period. CONCLUSIONS: The immediate effects of the brief delivery of EMT were not
      sustained over the 1-year follow-up period. However, the short-term intervention
      may not have been sufficient for children with receptive-expressive delays to
      develop typical language abilities, suggesting they may need more intensive early
      intervention. Although this intervention may not be necessary for all children
      with primary language delays, future research should determine the extent to
      which children with receptive-expressive delays may benefit from more intensive
      intervention.

PMID- 29054978
TI  - Breast Cancer in Latinas: A Focus on Intrinsic Subtypes Distribution.
AB  - Breast cancer is the most frequent cancer in women worldwide. It is classified
      into intrinsic subtypes characterized by different molecular profiles and
      prognosis. The prevalence of the different intrinsic subtypes varies between
      population groups. IHC surrogates based on the expression of the estrogen
      receptor, progesterone receptor, and HER2 have been widely used to study the
      distribution of intrinsic subtypes in non-Hispanic whites and African Americans,
      but data are limited for Hispanic/Latina women. Similarly, most studies analyzing
      gene expression profiles only include women of European descent. This review
      focuses on studies that describe the distribution of breast cancer subtypes in
      Hispanic/Latina women and highlights the need for more research in this
      population. Cancer Epidemiol Biomarkers Prev; 27(1); 3-10. (c)2017 AACR.

PMID- 29054981
TI  - Immunoadsorption in Anti-GBM Glomerulonephritis: Case Report in a Child and
      Literature Review.
AB  - Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a rare
      autoimmune disease that is characterized by rapidly progressive
      glomerulonephritis that may be associated with pulmonary hemorrhage. Anti-GBM GN
      is caused by autoantibodies (classically type G immunoglobulin) directed against
      the alpha3 subunit of type IV collagen. Without any appropriate treatment, the
      disease is generally fulminant, and patient and kidney survival is poor. The
      current guidelines recommend the use of plasma exchanges and immunosuppressive
      drugs. Immunoadsorption (IA) can remove pathogenic IgGs from the circulation and
      do not require plasma infusions, contrary to plasma exchanges. IA has seldom been
      used in adult patients with good tolerance and efficiency. We report herein the
      first pediatric case successfully treated with IA combined with immunosuppressive
      drugs in a 7-year-old girl who presented acute kidney injury (estimated
      glomerular filtration rate 38 mL/minute/1.73 m2). A kidney biopsy revealed
      numerous >80% glomerular crescents and linear IgG deposits along the glomerular
      basement membrane. Ten IA sessions led to rapid and sustained clearance of
      autoantibodies and improvement of kidney function until 21 months after onset
      (glomerular filtration rate 87 mL/minute/1.73 m2). No adverse effect was noted.
      This report adds to the growing body of evidence suggesting IA as a therapeutic
      alternative to plasma exchanges in anti-GBM GN. The other 27 published pediatric
      cases of anti-GBM GN are reviewed.

PMID- 29054982
TI  - Discovery of a Highly Selective NAMPT Inhibitor That Demonstrates Robust Efficacy
      and Improved Retinal Toxicity with Nicotinic Acid Coadministration.
AB  - NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as
      an anticancer target for developing potential novel therapeutics. Several NAMPT
      inhibitors have been discovered, some of which have been subjected to clinical
      investigations. Yet, the on-target hematological and retinal toxicities have
      hampered their clinical development. In this study, we report the discovery of a
      unique NAMPT inhibitor, LSN3154567. This molecule is highly selective and has a
      potent and broad spectrum of anticancer activity. Its inhibitory activity can be
      rescued with nicotinic acid (NA) against the cell lines proficient, but not those
      deficient in NAPRT1, essential for converting NA to NAD+ LSN3154567 also exhibits
      robust efficacy in multiple tumor models deficient in NAPRT1. Importantly, this
      molecule when coadministered with NA does not cause observable retinal and
      hematological toxicities in the rodents, yet still retains robust efficacy. Thus,
      LSN3154567 has the potential to be further developed clinically into a novel
      cancer therapeutic. Mol Cancer Ther; 16(12); 2677-88. (c)2017 AACR.

PMID- 29054983
TI  - ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK
      Isoforms.
AB  - Oncogenic ALK fusions occur in several types of cancer and can be effectively
      treated with ALK inhibitors; however, ALK fusions and treatment response have not
      been characterized in malignant melanomas. Recently, a novel isoform of ALK
      (ALKATI ) was reported in 11% of melanomas but the response of melanomas
      expressing ALKATI to ALK inhibition has not been well characterized. We analyzed
      45 melanoma patient-derived xenograft models for ALK mRNA and protein expression.
      ALK expression was identified in 11 of 45 (24.4%) melanomas. Ten melanomas
      express wild-type (wt) ALK and/or ALKATI and one mucosal melanoma expresses
      multiple novel EML4-ALK fusion variants. Melanoma cells expressing different ALK
      variants were tested for response to ALK inhibitors. Whereas the melanoma
      expressing EML4-ALK were sensitive to ALK inhibitors in vitro and in vivo, the
      melanomas expressing wt ALK or ALKATI were not sensitive to ALK inhibitors. In
      addition, a patient with mucosal melanoma expressing ALKATI was treated with an
      ALK/ROS1/TRK inhibitor (entrectinib) on a phase I trial but did not respond. Our
      results demonstrate ALK fusions occur in malignant melanomas and respond to
      targeted therapy, whereas melanomas expressing ALKATI do not respond to ALK
      inhibitors. Targeting ALK fusions is an effective therapeutic option for a subset
      of melanoma patients, but additional clinical studies are needed to determine the
      efficacy of targeted therapies in melanomas expressing wt ALK or ALKATIMol Cancer
      Ther; 17(1); 222-31. (c)2017 AACR.

PMID- 29054985
TI  - Caveolae-Mediated Endocytosis as a Novel Mechanism of Resistance to Trastuzumab
      Emtansine (T-DM1).
AB  - Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that has
      demonstrated clinical benefit for patients with HER2+ metastatic breast cancer;
      however, its clinical activity is limited by inherent or acquired drug
      resistance. The molecular mechanisms that drive clinical resistance to T-DM1,
      especially in HER2+ tumors, are not well understood. We used HER2+ cell lines to
      develop models of T-DM1 resistance using a cyclical dosing schema in which cells
      received T-DM1 in an "on-off" routine until a T-DM1-resistant population was
      generated. T-DM1-resistant N87 cells (N87-TM) were cross-resistant to a panel of
      trastuzumab-ADCs (T-ADCs) with non-cleavable-linked auristatins. N87-TM cells do
      not have a decrease in HER2 protein levels or an increase in drug transporter
      protein (e.g., MDR1) expression compared with parental N87 cells. Intriguingly, T
      ADCs using auristatin payloads attached via an enzymatically cleavable linker
      overcome T-DM1 resistance in N87-TM cells. Importantly, N87-TM cells implanted
      into athymic mice formed T-DM1 refractory tumors that remain sensitive to T-ADCs
      with cleavable-linked auristatin payloads. Comparative proteomic profiling
      suggested enrichment in proteins that mediate caveolae formation and endocytosis
      in the N87-TM cells. Indeed, N87-TM cells internalize T-ADCs into intracellular
      caveolin-1 (CAV1)-positive puncta and alter their trafficking to the lysosome
      compared with N87 cells. T-DM1 colocalization into intracellular CAV1-positive
      puncta correlated with reduced response to T-DM1 in a panel of HER2+ cell lines.
      Together, these data suggest that caveolae-mediated endocytosis of T-DM1 may
      serve as a novel predictive biomarker for patient response to T-DM1. Mol Cancer
      Ther; 17(1); 243-53. (c)2017 AACR.

PMID- 29054984
TI  - Overcoming Resistance to Cetuximab with Honokiol, A Small-Molecule Polyphenol.
AB  - Overexpression and activation of the EGFR have been linked to poor prognosis in
      several human cancers. Cetuximab is a mAb against EGFR that is used for the
      treatment in head and neck squamous cell carcinoma (HNSCC) and metastatic
      colorectal cancer. Unfortunately, most tumors have intrinsic or will acquire
      resistance to cetuximab during the course of therapy. Honokiol is a natural
      compound found in the bark and leaves of the Chinese Magnolia tree and is
      established to have several anticancer properties without appreciable toxicity.
      In this study, we hypothesized that combining cetuximab and honokiol treatments
      could overcome acquired resistance to cetuximab. We previously developed a model
      of acquired resistance to cetuximab in non-small cell lung cancer H226 cell line.
      Treatment of cetuximab-resistant clones with honokiol and cetuximab resulted in a
      robust antiproliferative response. Immunoblot analysis revealed the HER family
      and their signaling pathways were downregulated after combination treatment, most
      notably the proliferation (MAPK) and survival (AKT) pathways. In addition, we
      found a decrease in phosphorylation of DRP1 and reactive oxygen species after
      combination treatment in cetuximab-resistant clones, which may signify a change
      in mitochondrial function. Furthermore, we utilized cetuximab-resistant HNSCC
      patient-derived xenografts (PDX) to test the benefit of combinatorial treatment
      in vivo There was significant growth delay in PDX tumors after combination
      treatment with a subsequent downregulation of active MAPK, AKT, and DRP1
      signaling as seen in vitro Collectively, these data suggest that honokiol is a
      promising natural compound in overcoming acquired resistance to cetuximab. Mol
      Cancer Ther; 17(1); 204-14. (c)2017 AACR.

PMID- 29054986
TI  - Phase I Study of Enavatuzumab, a First-in-Class Humanized Monoclonal Antibody
      Targeting the TWEAK Receptor, in Patients with Advanced Solid Tumors.
AB  - This phase I study evaluates the safety, MTD, pharmacokinetics (PK),
      pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a
      humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid
      malignancies. Patients received escalating doses of enavatuzumab given
      intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and
      biomarker assessment. Three patients were enrolled per dose level in a standard
      3+3 design with response assessment by RECIST version 1.0, every 8 weeks. Thirty
      patients were enrolled at 6 dose levels ranging from 0.1 to 1.5 mg/kg. Dose
      limiting toxicities included grade 4 (G4) lipase, G3 bilirubin, and G4 amylase
      elevations. There was no apparent correlation of liver or pancreatic enzyme
      elevation with drug exposure or the presence of liver metastases. Enavatuzumab
      exhibited a two-compartment linear PK model. Estimated systemic clearance was 23
      to 33 mL/h with an elimination half-life of 7 to 18 days. The predicted target
      efficacious peak and trough concentrations occurred at 1.0 mg/kg following the
      second dose. There were no objective responses; 4 patients had stable disease.
      The MTD of enavatuzumab is 1.0 mg/kg i.v. every 2 weeks. Higher doses were not
      tolerated due to hepatopancreatic lab abnormalities. Further evaluation of the
      mechanisms of the liver and pancreatic enzyme toxicities is needed before
      embarking on further single-agent or combination strategies. Mol Cancer Ther;
      17(1); 215-21. (c)2017 AACR.

PMID- 29054987
TI  - Theranostic Radiolabeled Anti-CD20 sdAb for Targeted Radionuclide Therapy of Non
      Hodgkin Lymphoma.
AB  - Anti-CD20 radioimmunotherapy is an effective approach for therapy of relapsed or
      refractory CD20pos lymphomas, but faces limitations due to poor tumor penetration
      and undesirable pharmacokinetics of full antibodies. Camelid single-domain Ab
      fragments (sdAb) might circumvent some of the limitations of radiolabeled full
      antibodies. In this study, a set of hCD20-targeting sdAbs was generated, and
      their capacity to bind hCD20 was evaluated in vitro and in vivo A lead sdAb, sdAb
      9079, was selected on the basis of its specific tumor targeting and significant
      lower kidney accumulation compared with other sdAbs. SdAb 9079 was then
      radiolabeled with 68Ga and 177Lu for PET imaging and targeted therapy. The
      therapeutic potential of 177Lu-DTPA-sdAb was compared with that of 177Lu-DTPA
      rituximab and unlabeled rituximab in mice bearing hCD20pos tumors. Radiolabeled
      with 68Ga, sdAb 9079 showed specific tumor uptake, with very low accumulation in
      nontarget organs, except kidneys. The tumor uptake of 177Lu-DTPA-sdAb 9079 after
      1.5 h was 3.4 +/- 1.3% ID/g, with T/B and T/M ratios of 13.3 +/- 4.6 and 32.9 +/-
      15.6. Peak tumor accumulation of 177Lu-DTPA-rituximab was about 9 times higher,
      but concomitantly with high accumulation in nontarget organs and very low T/B and
      T/M ratios (0.8 +/- 0.1 and 7.1 +/- 2.4). Treatment of mice with 177Lu-DTPA-sdAb
      9079 significantly prolonged median survival compared with control groups and was
      as effective as treatment with rituximab or its 177Lu-labeled variant. Taken
      together, sdAb 9079 displays promising features as a theranostic drug to treat
      CD20pos lymphomas. Mol Cancer Ther; 16(12); 2828-39. (c)2017 AACR.

PMID- 29054988
TI  - AKT1low Quiescent Cancer Cells Promote Solid Tumor Growth.
AB  - Human tumor growth depends on rapidly dividing cancer cells driving population
      expansion. Even advanced tumors, however, contain slowly proliferating cancer
      cells for reasons that remain unclear. Here, we selectively disrupt the ability
      of rapidly proliferating cancer cells to spawn AKT1low daughter cells that are
      rare, slowly proliferating, tumor-initiating, and chemotherapy-resistant, using
      beta1-integrin activation and the AKT1-E17K-mutant oncoprotein as experimental
      tools in vivo Surprisingly, we find that selective depletion of AKT1low slow
      proliferators actually reduces the growth of a molecularly diverse panel of human
      cancer cell xenograft models without globally altering cell proliferation or
      survival in vivo Moreover, we find that unusual cancer patients with AKT1-E17K
      mutant solid tumors also fail to produce AKT1low quiescent cancer cells and that
      this correlates with significantly prolonged survival after adjuvant treatment
      compared with other patients. These findings support a model whereby human solid
      tumor growth depends on not only rapidly proliferating cancer cells but also on
      the continuous production of AKT1low slow proliferators. Mol Cancer Ther; 17(1);
      254-63. (c)2017 AACR.

PMID- 29054990
TI  - How 3D patient-specific instruments improve accuracy of pelvic bone tumour
      resection in a cadaveric study.
AB  - OBJECTIVES: To assess the accuracy of patient-specific instruments (PSIs) versus
      standard manual technique and the precision of computer-assisted planning and PSI
      guided osteotomies in pelvic tumour resection. METHODS: CT scans were obtained
      from five female cadaveric pelvises. Five osteotomies were designed using Mimics
      software: sacroiliac, biplanar supra-acetabular, two parallel iliopubic and
      ischial. For cases of the left hemipelvis, PSIs were designed to guide standard
      oscillating saw osteotomies and later manufactured using 3D printing. Osteotomies
      were performed using the standard manual technique in cases of the right
      hemipelvis. Post-resection CT scans were quantitatively analysed. Student's t
      test and Mann-Whitney U test were used. RESULTS: Compared with the manual
      technique, PSI-guided osteotomies improved accuracy by a mean 9.6 mm (p < 0.008)
      in the sacroiliac osteotomies, 6.2 mm (p < 0.008) and 5.8 mm (p < 0.032) in the
      biplanar supra-acetabular, 3 mm (p < 0.016) in the ischial and 2.2 mm (p < 0.032)
      and 2.6 mm (p < 0.008) in the parallel iliopubic osteotomies, with a mean linear
      deviation of 4.9 mm (p < 0.001) for all osteotomies. Of the manual osteotomies,
      53% (n = 16) had a linear deviation > 5 mm and 27% (n = 8) were > 10 mm. In the
      PSI cases, deviations were 10% (n = 3) and 0 % (n = 0), respectively. For angular
      deviation from pre-operative plans, we observed a mean improvement of 7.06
      degrees  (p < 0.001) in pitch and 2.94 degrees  (p < 0.001) in roll, comparing
      PSI and the standard manual technique. CONCLUSION: In an experimental study,
      computer-assisted planning and PSIs improved accuracy in pelvic tumour
      resections, bringing osteotomy results closer to the parameters set in pre
      operative planning, as compared with standard manual techniques.Cite this
      article: A. Sallent, M. Vicente, M. M. Reverte, A. Lopez, A. Rodriguez-Baeza, M.
      Perez-Dominguez, R. Velez. How 3D patient-specific instruments improve accuracy
      of pelvic bone tumour resection in a cadaveric study. Bone Joint Res 2017;6:577
      583. DOI: 10.1302/2046-3758.610.BJR-2017-0094.R1.

PMID- 29054991
TI  - The influence of bone mineral density and cortical index on the complexity of
      fractures of the proximal humerus.
AB  - OBJECTIVES: The goal of this study is to investigate the relation between
      indicators of osteoporosis (i.e., bone mineral density (BMD), and Cortical Index
      (CI)) and the complexity of a fracture of the proximal humerus as a result of a
      low-energy trauma. METHODS: A retrospective chart review of 168 patients (mean
      age 67.2 years, range 51 to 88.7) with a fracture of the proximal humerus between
      2007 and 2011, whose BMD was assessed at the Fracture Liaison Service with Dual
      Energy X-ray Absorptiometry (DXA) measurements of the hip, femoral neck (FN)
      and/or lumbar spine (LS), and whose CI and complexity of fracture were assessed
      on plain anteroposterior radiographs of the proximal humerus. RESULTS: No
      significant differences were found between simple and complex fractures of the
      proximal humerus in the BMD of the hip, FN or LS (all p > 0.3) or in the CI (p =
      0.14). Only the body mass index was significantly higher in patients with a
      complex fracture compared with those with a simple fracture (26.9 vs 25.2; p =
      0.05). CONCLUSION: There was no difference in BMD of the hip, FN, LS or CI of the
      proximal humerus in simple compared with complex fractures of the proximal
      humerus after a low-energy trauma. Factors other than the BMD and CI, for example
      body mass index, may play a more important role in the complexity of this
      fracture.Cite this article: J.W.A.M. den Teuling, B.S. Pauwels, L. Janssen, C.E.
      Wyers, H. M. J. Janzing, J.P.W. van den Bergh, J. W. Morrenhof. The Influence of
      bone mineral density and cortical index on the complexity of fractures of the
      proximal humerus. Bone Joint Res 2017;6:584-589. DOI: 10.1302/2046-3758.610.BJR
      2017-0080.

PMID- 29054994
TI  - Subtypes of Pediatric High-Grade Gliomas ID'd.
AB  - A molecular analysis that included genome sequencing, methylation profiling, and
      copy-number analysis divides pediatric glioma into 10 different categories.
      Tumors in each category carry distinct mutations, grow in different parts of the
      brain, and have varying impact on survival. The findings could lead to more
      effective treatments.

PMID- 29054992
TI  - Suppression of Adaptive Responses to Targeted Cancer Therapy by Transcriptional
      Repression.
AB  - Acquired drug resistance is a major factor limiting the effectiveness of targeted
      cancer therapies. Targeting tumors with kinase inhibitors induces complex
      adaptive programs that promote the persistence of a fraction of the original cell
      population, facilitating the eventual outgrowth of inhibitor-resistant tumor
      clones. We show that the addition of a newly identified CDK7/12 inhibitor, THZ1,
      to targeted therapy enhances cell killing and impedes the emergence of drug
      resistant cell populations in diverse cellular and in vivo cancer models. We
      propose that targeted therapy induces a state of transcriptional dependency in a
      subpopulation of cells poised to become drug tolerant, which THZ1 can exploit by
      blocking dynamic transcriptional responses, promoting remodeling of enhancers and
      key signaling outputs required for tumor cell survival in the setting of targeted
      therapy. These findings suggest that the addition of THZ1 to targeted therapies
      is a promising broad-based strategy to hinder the emergence of drug-resistant
      cancer cell populations.Significance: CDK7/12 inhibition prevents active enhancer
      formation at genes, promoting resistance emergence in response to targeted
      therapy, and impedes the engagement of transcriptional programs required for
      tumor cell survival. CDK7/12 inhibition in combination with targeted cancer
      therapies may serve as a therapeutic paradigm for enhancing the effectiveness of
      targeted therapies. Cancer Discov; 8(1); 59-73. (c)2017 AACR.See related
      commentary by Carugo and Draetta, p. 17This article is highlighted in the In This
      Issue feature, p. 1.

PMID- 29054999
TI  - A molecular basis of human T cell receptor autoreactivity toward self
      phospholipids.
AB  - Human T cell autoreactivity toward lipid antigens presented by CD1 proteins can
      manifest in numerous diseases, including psoriasis, contact hypersensitivities,
      and allergies. However, the molecular mechanisms for regulating T cell
      autoreactivity toward lipid antigens remain unclear. We determined the basis for
      T cell receptor (TCR) autoreactivity toward CD1b bound to self-phospholipids. The
      spectrum of self-antigens captured by CD1b skews toward abundant membrane
      phospholipids such as phosphatidylcholine and phosphatidylethanolamine. However,
      TCRs can specifically recognize rare phospholipids, including
      phosphatidylglycerol (PG). The structure of an autoreactive TCR bound to CD1b-PG
      shows that discrimination occurs through a marked induced fit movement of PG so
      that its polar head group fits snugly into the cationic cup of the TCR.
      Conversely, TCR binding toward ubiquitous self-phospholipids was sterically or
      electrostatically repelled. Accordingly, we describe a mechanism of TCR
      autoreactivity toward rare phospholipids and avoidance of autoreactivity to the
      most abundant self-phospholipids.

PMID- 29054998
TI  - Interleukin-10 from CD4+ follicular regulatory T cells promotes the germinal
      center response.
AB  - CD4+ follicular regulatory T (Tfr) cells suppress B cell responses through
      modulation of follicular helper T (Tfh) cells and germinal center (GC)
      development. We found that Tfr cells can also promote the GC response through
      provision of interleukin-10 (IL-10) after acute infection with lymphocytic
      choriomeningitis virus (LCMV). Sensing of IL-10 by B cells was necessary for
      optimal development of the GC response. GC B cells formed in the absence of Treg
      cell-derived IL-10 displayed an altered dark zone state and decreased expression
      of the transcription factor Forkhead box protein 1 (FOXO1). IL-10 promoted
      nuclear translocation of FOXO1 in activated B cells. These data indicate that Tfr
      cells play a multifaceted role in the fine-tuning of the GC response and identify
      IL-10 as an important mediator by which Tfr cells support the GC reaction.

PMID- 29055000
TI  - Special issue on molecular and cellular cognition.

PMID- 29055001
TI  - Listeria monocytogenes Replicate in Bone Marrow-Derived CD11c+ Cells but Not in
      Dendritic Cells Isolated from the Murine Gastrointestinal Tract.
AB  - Recent fate-mapping studies and gene-expression profiles suggest that commonly
      used protocols to generate bone marrow-derived cultured dendritic cells yield a
      heterogeneous mixture, including some CD11chi cells that may not have a bona fide
      counterpart in vivo. In this study, we provide further evidence of the
      discordance between ex vivo-isolated and in vitro-cultured CD11c+ cells by
      analyzing an additional phenotype, the ability to support cytosolic growth of the
      facultative intracellular bacterial pathogen Listeria monocytogenes Two days
      after foodborne infection of mice with GFP-expressing L. monocytogenes, a small
      percentage of CD103neg and CD103+ conventional dendritic cells (cDC) in the
      intestinal lamina propria and mesenteric lymph nodes were GFP+ However, in vitro
      infection of the same subsets of cells harvested from naive mice resulted in
      inefficient invasion by the bacteria (<0.1% of the inoculum). The few
      intracellular bacteria detected survived for only a few hours. In contrast,
      cultured CD103negCD11c+ cells induced by GM-CSF readily supported exponential
      growth of L. monocytogenes Flt3 ligand-induced cultures yielded CD103+CD11c+
      cells that more closely resembled cDC, with only a modest level of L.
      monocytogenes replication. For both culture protocols, the longer the cells were
      maintained in vitro, the more readily they supported intracellular growth. The
      results of this study suggest that cDC are not a niche for intracellular growth
      of L. monocytogenes during intestinal infection of mice.

PMID- 29055003
TI  - Anti-CD20 Antibody Prevents Red Blood Cell Alloimmunization in a Mouse Model.
AB  - Alloimmunization against RBCs can cause life-threatening delayed hemolytic
      transfusion reactions. Anti-CD20 Ab has recently been used to prevent
      alloimmunization. However, its effects remain unclear, particularly in lymphoid
      organs. We investigated the impact of murine anti-CD20 Ab in the blood and
      spleen. We assessed protocols for preventing primary alloimmunization and for
      abolishing established alloimmunization. Prophylactic protocols prevented
      alloimmunization. However, anti-CD20 treatment could only limit the further
      amplification of established alloimmunization. Residual B cell subtype
      distribution was disrupted in the spleen, but adoptive transfer studies indicated
      that these cells were neither plasma nor memory cells. Anti-CD20 Ab had a major
      effect on alloreactive CD4+ T cells, increasing the expansion of this population
      and its CD40 expression, while lowering its CD134 expression, thereby confirming
      its role in alloimmunization. In conclusion, this study shows that anti-CD20
      immunotherapy can prevent RBC Ab development. However, this immunotherapy is
      limited by the increase in alloreactive CD4+ T lymphocytes. Nevertheless,
      treatment with anti-CD20 Abs should be considered for patients requiring
      transfusion with a very high risk of alloimmunization and life-threatening
      complications.

PMID- 29055002
TI  - Transient BAFF Blockade Inhibits Type 1 Diabetes Development in Nonobese Diabetic
      Mice by Enriching Immunoregulatory B Lymphocytes Sensitive to Deletion by Anti
      CD20 Cotherapy.
AB  - In NOD mice and also likely humans, B lymphocytes play an important role as APC
      expanding autoreactive T cell responses ultimately causing type 1 diabetes (T1D).
      Currently, humans at high future T1D risk can only be identified at late
      prodromal stages of disease indicated by markers such as insulin autoantibodies.
      When commenced in already insulin autoantibody+ NOD mice, continuous BAFFR-Fc
      treatment alone or in combination with anti-CD20 (designated combo therapy)
      inhibited T1D development. Despite eliciting broader B lymphocyte depletion,
      continuous combo therapy afforded no greater T1D protection than did BAFFR-Fc
      alone. As previously observed, late disease stage-initiated anti-CD20 monotherapy
      did not inhibit T1D, and in this study was additionally found to be associated
      with development of drug-blocking Abs. Promisingly, NOD mice given transient late
      disease stage BAFFR-Fc monotherapy were rendered T1D resistant. However, combo
      treatment abrogated the protective effect of transient BAFFR-Fc monotherapy. NOD
      mice receiving transient BAFF blockade were characterized by an enrichment of
      regulatory B lymphocytes that inhibit T1D development through IL-10 production,
      but this population is sensitive to deletion by anti-CD20 treatment. B
      lymphocytes from transient BAFFR-Fc-treated mice suppressed T cell proliferation
      to a greater extent than did those from controls. Proportions of B lymphocytes
      expressing CD73, an ecto-enzyme operating in a pathway converting proinflammatory
      ATP to anti-inflammatory adenosine, were also temporarily increased by transient
      BAFFR-Fc treatment, but not anti-CD20 therapy. These collective studies indicate
      transient BAFFR-Fc-mediated B lymphocyte depletion elicits long-term T1D
      protection by enriching regulatory B lymphocytes that are deleted by anti-CD20
      cotherapy.

PMID- 29055004
TI  - STAT4 Regulates the CD8+ Regulatory T Cell/T Follicular Helper Cell Axis and
      Promotes Atherogenesis in Insulin-Resistant Ldlr-/- Mice.
AB  - The metabolic syndrome and diabetic conditions support atherosclerosis, but the
      exact mechanisms for accelerated atherogenesis remain unclear. Although the
      proinflammatory role of STAT4 in atherosclerosis and diet-induced insulin
      resistance (IR) was recently established, the impact of STAT4 on atherogenesis in
      conditions of IR is not known. In this study, we generated Stat4-/-Ldlr-/- mice
      that were fed a diabetogenic diet with added cholesterol (DDC). DDC-fed Stat4-/
      Ldlr-/- mice demonstrated improved glucose tolerance, insulin sensitivity, and a
      36% reduction in atherosclerosis compared with Ldlr-/- controls. Interestingly,
      we detected a reduction in T follicular helper (Tfh) cells and plasma B cells but
      a sharp elevation in CD8+ regulatory T cells (Tregs) in spleens and aortas of
      Stat4-/-Ldlr-/- mice compared with Ldlr-/- mice. Similarly, STAT4 deficiency
      supported CD8+ Treg differentiation in vitro. STAT4-deficient CD8+ Tregs
      suppressed Tfh cell and germinal center B cell development upon immunization with
      keyhole limpet hemocyanin, indicating an important role for STAT4 in CD8+ Treg
      functions in vivo. Furthermore, adoptive transfer of Stat4-/-Ldlr-/- CD8+ Tregs
      versus Ldlr-/- CD8+ Tregs resulted in a significant reduction in plaque burden
      and suppression of Tfh cell and germinal center B cells in DDC-fed Ldlr-/-
      recipients. STAT4 expression in macrophages (MPhis) also affected the Tfh/CD8+
      Treg axis, because conditioned media from Stat4-/-Ldlr-/- MPhis supported CD8+
      Treg differentiation, but not Tfh cell differentiation, in a TGF-beta-dependent
      manner. These findings suggest a novel mechanism by which STAT4 supports
      atherosclerosis in IR Ldlr-/- mice via STAT4-dependent MPhis, as well as cell
      intrinsic suppression of CD8+ Treg generation and functions and maintenance of
      Tfh cell generation and the accompanying humoral immune response.

PMID- 29055005
TI  - Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR
      Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I
      IFN.
AB  - Type I IFN and nucleic acid-sensing TLRs are both strongly implicated in the
      pathogenesis of lupus, with most patients expressing IFN-induced genes in
      peripheral blood cells and with TLRs promoting type I IFNs and autoreactive B
      cells. About a third of systemic lupus erythematosus patients, however, lack the
      IFN signature, suggesting the possibility of type I IFN-independent mechanisms.
      In this study, we examined the role of type I IFN and TLR trafficking and
      signaling in xenobiotic systemic mercury-induced autoimmunity (HgIA). Strikingly,
      autoantibody production in HgIA was not dependent on the type I IFN receptor even
      in NZB mice that require type I IFN signaling for spontaneous disease, but was
      dependent on the endosomal TLR transporter UNC93B1 and the endosomal proton
      transporter, solute carrier family 15, member 4. HgIA also required the adaptor
      protein-3 complex, which transports TLRs from the early endosome to the late
      endolysosomal compartments. Examination of TLR signaling pathways implicated the
      canonical NF-kappaB pathway and the proinflammatory cytokine IL-6 in autoantibody
      production, but not IFN regulatory factor 7. These findings identify HgIA as a
      novel type I IFN-independent model of systemic autoimmunity and implicate TLR
      mediated NF-kappaB proinflammatory signaling from the late endocytic pathway
      compartments in autoantibody generation.

PMID- 29055008
TI  - Northern Irish GPs warn patients that workforce crisis may mean turning them
      away.

PMID- 29055006
TI  - Posttranscriptional Regulation of HLA-A Protein Expression by Alternative
      Polyadenylation Signals Involving the RNA-Binding Protein Syncrip.
AB  - Genomic variation in the untranslated region (UTR) has been shown to influence
      HLA class I expression level and associate with disease outcomes. Sequencing of
      the 3'UTR of common HLA-A alleles indicated the presence of two polyadenylation
      signals (PAS). The proximal PAS is conserved, whereas the distal PAS is disrupted
      within certain alleles by sequence variants. Using 3'RACE, we confirmed
      expression of two distinct forms of the HLA-A 3'UTR based on use of either the
      proximal or the distal PAS, which differ in length by 100 bp. Specific HLA-A
      alleles varied in the usage of the proximal versus distal PAS, with some alleles
      using only the proximal PAS, and others using both the proximal and distal PAS to
      differing degrees. We show that the short and the long 3'UTR produced similar
      mRNA expression levels. However, the long 3'UTR conferred lower luciferase
      activity as compared with the short form, indicating translation inhibition of
      the long 3'UTR. RNA affinity pull-down followed by mass spectrometry analysis as
      well as RNA coimmunoprecipitation indicated differential binding of Syncrip to
      the long versus short 3'UTR. Depletion of Syncrip by small interfering RNA
      increased surface expression of an HLA-A allotype that uses primarily the long
      3'UTR, whereas an allotype expressing only the short form was unaffected.
      Furthermore, specific blocking of the proximal 3'UTR reduced surface expression
      without decreasing mRNA expression. These data demonstrate HLA-A allele-specific
      variation in PAS usage, which modulates their cell surface expression
      posttranscriptionally.

PMID- 29055007
TI  - The Structure of the MHC Class I Molecule of Bony Fishes Provides Insights into
      the Conserved Nature of the Antigen-Presenting System.
AB  - MHC molecules evolved with the descent of jawed fishes some 350-400 million years
      ago. However, very little is known about the structural features of primitive MHC
      molecules. To gain insight into these features, we focused on the MHC class I
      Ctid-UAA of the evolutionarily distant grass carp (Ctenopharyngodon idella). The
      Ctid-UAA H chain and beta2-microglobulin (Ctid-beta2m) were refolded in vitro in
      the presence of peptides from viruses that infect carp. The resulting peptide
      Ctid-UAA (p/Ctid-UAA) structures revealed the classical MHC class I topology with
      structural variations. In comparison with known mammalian and chicken peptide-MHC
      class I (p/MHC I) complexes, p/Ctid-UAA structure revealed several distinct
      features. Notably, 1) although the peptide ligand conventionally occupied all six
      pockets (A-F) of the Ag-binding site, the binding mode of the P3 side chain to
      pocket D was not observed in other p/MHC I structures; 2) the AB loop between
      beta strands of the alpha1 domain of p/Ctid-UAA complex comes into contact with
      Ctid-beta2m, an interaction observed only in chicken p/BF2*2101-beta2m complex;
      and 3) the CD loop of the alpha3 domain, which in mammals forms a contact with
      CD8, has a unique position in p/Ctid-UAA that does not superimpose with the
      structures of any known p/MHC I complexes, suggesting that the p/Ctid-UAA to Ctid
      CD8 binding mode may be distinct. This demonstration of the structure of a bony
      fish MHC class I molecule provides a foundation for understanding the evolution
      of primitive class I molecules, how they present peptide Ags, and how they might
      control T cell responses.

PMID- 29055009
TI  - In search of regulatory circuits that control the biological activity of vitamin
      D.
AB  - Although the cytochrome P450 CYP27B1 plays a critical role in vitamin D biology,
      the molecular mechanisms involved in regulation of CYP27B1 have remained
      undefined. A new study has identified a kidney-specific control module distal to
      the Cyp27b1 gene that mediates the basal activity and hormonal regulation of
      Cyp27b1 This work provides a novel mechanism indicating differential regulation
      of Cyp27b1 in renal and non-renal cells and has implications for vitamin D
      biology in multiple sclerosis and perhaps other autoimmune diseases as well.

PMID- 29055010
TI  - An excitable Rho GTPase signaling network generates dynamic subcellular
      contraction patterns.
AB  - Rho GTPase-based signaling networks control cellular dynamics by coordinating
      protrusions and retractions in space and time. Here, we reveal a signaling
      network that generates pulses and propagating waves of cell contractions. These
      dynamic patterns emerge via self-organization from an activator-inhibitor
      network, in which the small GTPase Rho amplifies its activity by recruiting its
      activator, the guanine nucleotide exchange factor GEF-H1. Rho also inhibits
      itself by local recruitment of actomyosin and the associated RhoGAP Myo9b. This
      network structure enables spontaneous, self-limiting patterns of subcellular
      contractility that can explore mechanical cues in the extracellular environment.
      Indeed, actomyosin pulse frequency in cells is altered by matrix elasticity,
      showing that coupling of contractility pulses to environmental deformations
      modulates network dynamics. Thus, our study reveals a mechanism that integrates
      intracellular biochemical and extracellular mechanical signals into subcellular
      activity patterns to control cellular contractility dynamics.

PMID- 29055011
TI  - UNC-45a promotes myosin folding and stress fiber assembly.
AB  - Contractile actomyosin bundles, stress fibers, are crucial for adhesion,
      morphogenesis, and mechanosensing in nonmuscle cells. However, the mechanisms by
      which nonmuscle myosin II (NM-II) is recruited to those structures and assembled
      into functional bipolar filaments have remained elusive. We report that UNC-45a
      is a dynamic component of actin stress fibers and functions as a myosin chaperone
      in vivo. UNC-45a knockout cells display severe defects in stress fiber assembly
      and consequent abnormalities in cell morphogenesis, polarity, and migration.
      Experiments combining structured-illumination microscopy, gradient
      centrifugation, and proteasome inhibition approaches revealed that a large
      fraction of NM-II and myosin-1c molecules fail to fold in the absence of UNC-45a.
      The remaining properly folded NM-II molecules display defects in forming
      functional bipolar filaments. The C-terminal UNC-45/Cro1/She4p domain of UNC-45a
      is critical for NM-II folding, whereas the N-terminal tetratricopeptide repeat
      domain contributes to the assembly of functional stress fibers. Thus, UNC-45a
      promotes generation of contractile actomyosin bundles through synchronized NM-II
      folding and filament-assembly activities.

PMID- 29055012
TI  - Type I interferon enhances necroptosis of Salmonella Typhimurium-infected
      macrophages by impairing antioxidative stress responses.
AB  - Salmonella enterica serovar Typhimurium exploits the host's type I interferon
      (IFN-I) response to induce receptor-interacting protein (RIP) kinase-mediated
      necroptosis in macrophages. However, the events that drive necroptosis execution
      downstream of IFN-I and RIP signaling remain elusive. In this study, we
      demonstrate that S Typhimurium infection causes IFN-I-mediated up-regulation of
      the mitochondrial phosphatase Pgam5 through RIP3. Pgam5 subsequently interacts
      with Nrf2, which sequesters Nrf2 in the cytosol, thereby repressing the
      transcription of Nrf2-dependent antioxidative genes. The impaired ability to
      respond to S Typhimurium-induced oxidative stress results in reactive oxygen
      species-mediated mitochondrial damage, energy depletion, transient induction of
      autophagy, and autophagic degradation of p62. Reduced p62 levels impair
      interaction of p62 with Keap1, which further decreases Nrf2 function and
      antioxidative responses to S Typhimurium infection, eventually leading to cell
      death. Collectively, we identify impaired Nrf2-dependent redox homeostasis as an
      important mechanism that promotes cell death downstream of IFN-I and RIP3
      signaling in S Typhimurium-infected macrophages.

PMID- 29055013
TI  - A Synthetic CD8alpha:MyD88 Coreceptor Enhances CD8+ T-cell Responses to Weakly
      Immunogenic and Lowly Expressed Tumor Antigens.
AB  - T cell-based immunotherapies are a promising approach for patients with advanced
      cancers. However, various obstacles limit T-cell efficacy, including suboptimal T
      cell receptor (TCR) activation and an immunosuppressive tumor environment. Here,
      we developed a fusion protein by linking CD8alpha and MyD88 (CD8alpha:MyD88) to
      enhance CD8+ T-cell responses to weakly immunogenic and poorly expressed tumor
      antigens. CD8alpha:MyD88-engineered T cells exhibited increased proliferation and
      expression of effector and costimulatory molecules in a tumor antigen-dependent
      manner. These effects were accompanied by elevated activation of TCR and Toll
      like receptor signaling-related proteins. CD8alpha:MyD88-expressing T cells
      improved antitumor responses in mice. Enhanced antitumor activity was associated
      with a unique tumor cytokine/chemokine signature, improved T-cell infiltration,
      reduced markers of T-cell exhaustion, elevated levels of proteins associated with
      antigen presentation, and fewer macrophages with an immunosuppressive phenotype
      in tumors. Given these observations, CD8alpha:MyD88 represents a unique and
      versatile approach to help overcome immunosuppression and enhance T-cell
      responses to tumor antigens. Cancer Res; 77(24); 7049-58. (c)2017 AACR.

PMID- 29055014
TI  - Protein Acyltransferase DHHC3 Regulates Breast Tumor Growth, Oxidative Stress,
      and Senescence.
AB  - DHHC-type protein acyltransferases may regulate the localization, stability,
      and/or activity of their substrates. In this study, we show that the protein
      palmitoyltransferase DHHC3 is upregulated in malignant and metastatic human
      breast cancer. Elevated expression of DHHC3 correlated with diminished patient
      survival in breast cancer and six other human cancer types. ZDHHC3 ablation in
      human MDA-MB-231 mammary tumor cell xenografts reduced the sizes of both the
      primary tumor and metastatic lung colonies. Gene array data and fluorescence dye
      assays documented increased oxidative stress and senescence in ZDHHC3-ablated
      cells. ZDHHC3-ablated tumors also showed enhanced recruitment of innate immune
      cells (antitumor macrophages, natural killer cells) associated with clearance of
      senescent tumors. These antitumor effects were reversed upon reconstitution with
      wild-type, but not enzyme-active site-deficient DHHC3. Concomitant ablation of
      the upregulated oxidative stress protein TXNIP substantially negated the effects
      of ZDHHC3 depletion on oxidative stress and senescence. Diminished DHHC3
      dependent palmitoylation of ERGIC3 protein likely played a key role in TXNIP
      upregulation. In conclusion, DHHC3-mediated protein palmitoylation supports
      breast tumor growth by modulating cellular oxidative stress and senescence.
      Cancer Res; 77(24); 6880-90. (c)2017 AACR.

PMID- 29055015
TI  - Small-Molecule Inhibition of PD-1 Transcription Is an Effective Alternative to
      Antibody Blockade in Cancer Therapy.
AB  - The impact of PD-1 immune checkpoint therapy prompts exploration of other
      strategies to downregulate PD-1 for cancer therapy. We previously showed that the
      serine/threonine kinase, glycogen synthase kinase, GSK-3alpha/beta, is a central
      regulator of PD-1 transcription in CD8+ T cells. Here, we show that the use of
      small-molecule inhibitors of GSK-3alpha/beta (GSK-3i) to reduce pcdc1 (PD-1)
      transcription and expression was as effective as anti-PD-1 and PD-L1-blocking
      antibodies in the control of B16 melanoma, or EL4 lymphoma, in primary tumor and
      metastatic settings. Furthermore, the conditional genetic deletion of GSK
      3alpha/beta reduced PD-1 expression on CD8+ T cells and limited B16 pulmonary
      metastasis to the same degree as PD-1 gene deficiency. In each model, GSK-3i
      inhibited PD-1 expression on tumor-infiltrating lymphocytes, while increasing
      Tbx21 (T-bet) transcription, and the expression of CD107a+ (LAMP1) and granzyme B
      (GZMB) on CD8+ T cells. Finally, the adoptive transfer of T cells treated ex vivo
      with a GSK-3 inhibitor delayed the onset of EL4 lymphoma growth to a similar
      extent as anti-PD-1 pretreatment. Overall, our findings show how GSK-3 inhibitors
      that downregulate PD-1 expression can enhance CD8+ T-cell function in cancer
      therapy to a similar degree as PD-1-blocking antibodies.Significance: These
      findings show how GSK-3 inhibitors that downregulate PD-1 expression can enhance
      CD8+ T-cell function in cancer therapy to a similar degree as PD-1 blocking
      antibodies, offering a next-generation approach in the design of
      immunotherapeutic approaches for cancer management. Cancer Res; 78(3); 706-17.
      (c)2017 AACR.

PMID- 29055016
TI  - SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K
      Mediated Tumor Development and Maintenance.
AB  - Activation of the PI3K-AKT signaling cascade is a common critical event during
      malignant transformation. In this study, we used thyroid gland epithelial cells
      and a series of genetically engineered mouse strains as model systems to
      demonstrate that, although necessary, AKT activation is not sufficient for PI3K
      driven transformation. Instead, transformation requires the activity of the PDK1
      regulated AGC family of protein kinases. In particular, SGK1 was found to be
      essential for proliferation and survival of thyroid cancer cells harboring PI3K
      activating mutations. Notably, cotargeting SGK1 and AKT resulted in significantly
      higher growth suppression than inhibiting either PI3K or AKT alone. Overall,
      these findings underscore the clinical relevance of AKT-independent pathways in
      tumors driven by genetic lesions targeting the PI3K cascade. Cancer Res; 77(24);
      6914-26. (c)2017 AACR.

PMID- 29055017
TI  - New Generation Nanomedicines Constructed from Self-Assembling Small-Molecule
      Prodrugs Alleviate Cancer Drug Toxicity.
AB  - The therapeutic index for chemotherapeutic drugs is determined in part by
      systemic toxicity, so strategies for dose intensification to improve efficacy
      must also address tolerability. In addressing this issue, we have investigated a
      novel combinatorial strategy of reconstructing a drug molecule and using
      sequential drug-induced nanoassembly to fabricate supramolecular nanomedicines
      (SNM). Using cabazitaxel as a target agent, we established that individual
      synthetic prodrugs tethered with polyunsaturated fatty acids were capable of
      recapitulating self-assembly behavior independent of exogenous excipients. The
      resulting SNM could be further refined by PEGylation with amphiphilic copolymers
      suitable for preclinical studies. Among these cabazitaxel derivatives,
      docosahexaenoic acid-derived compound 1 retained high antiproliferative activity.
      SNM assembled with compound 1 displayed an unexpected enhancement of tolerability
      in animals along with effective therapeutic efficacy in a mouse xenograft model
      of human cancer, compared with free drug administered in its clinical
      formulation. Overall, our studies showed how attaching flexible lipid chains to a
      hydrophobic and highly toxic anticancer drug can convert it to a systemic self
      deliverable nanotherapy, preserving its pharmacologic efficacy while improving
      its safety profile. Cancer Res; 77(24); 6963-74. (c)2017 AACR.

PMID- 29055018
TI  - RUNX1 Upregulation by Cytotoxic Drugs Promotes Apoptosis.
AB  - Mutations in the RUNX1 gene have been associated with chemotherapy resistance and
      poor prognosis in patients with acute myeloid leukemia (AML), T-cell acute
      lymphoblastic leukemia, and myelodysplastic syndromes. However, the underlying
      mechanisms connecting RUNX1 to the success of therapy remain elusive. Here we
      explore the hypothesis that RUNX1 is directly involved in the response of
      hematopoietic cells to cytotoxic agents. RUNX1 was upregulated
      posttranscriptionally by cytotoxic agents in C57BL/6 mice in vivo and
      hematopoietic cell lines. Upregulation was also seen in primary human AML cells
      after treatment with cytarabine in vitro Upon overexpression, RUNX1 restricted
      proliferation, promoted apoptosis, and augmented the DNA damage response. This
      unknown activity of RUNX1 required an intact runt homology domain (RHD), a domain
      where most leukemia-associated point mutations cluster. Consistent with this, two
      RHD-defective RUNX1 proteins lacked any antiproliferative or apoptotic activity,
      and RHD-defective (K83N, N109D) mutant RUNX1 conferred resistance to ionizing
      radiation when overexpressed in Ba/F3 cells under certain conditions. Our
      experiments reveal a novel function of RUNX1 and offer an explanation for the
      link between RUNX1 mutations and chemotherapy and radiation resistance. Moreover,
      these data suggest that pharmacologic modulation of RUNX1 might be an attractive
      new approach to treat hematologic malignancies. Cancer Res; 77(24); 6818-24.
      (c)2017 AACR.

PMID- 29055019
TI  - [18F]fluorothymidine PET Informs the Synergistic Efficacy of Capecitabine and
      Trifluridine/Tipiracil in Colon Cancer.
AB  - In cancer therapy, enhanced thymidine uptake by the salvage pathway can bypass
      dTMP depletion, thereby conferring resistance to thymidylate synthase inhibition.
      We investigated whether sequential combination therapy of capecitabine and
      trifluridine/tipiracil (TAS-102) could synergistically enhance antitumor efficacy
      in colon cancer xenograft models. We also examined 3'-deoxy-3'
      [18F]fluorothymidine ([18F]FLT) PET as a means to predict therapeutic response to
      a sequential combination of capecitabine and trifluridine/tipiracil. [3H]FLT
      uptake after 5-fluorouracil treatment in vitro and [18F]FLT uptake after
      capecitabine (360 mg/kg/day) in athymic nude mice (Balb/c-nu) with xenografts (n
      = 10-12 per group) were measured using eight human colon cancer cell lines. We
      determined the synergistic effects of sequential combinations of 5-fluorouracil
      and trifluridine in vitro as well as the sequential combination of oral
      capecitabine (30-360 mg/kg) and trifluridine/tipiracil (trifluridine 75 or 150
      mg/kg with tipiracil) in six xenograft models (n = 6-10 per group). We observed
      significant increases in [3H]FLT uptake in all cell lines and [18F]FLT uptake in
      five xenograft models after 5-fluorouracil and capecitabine treatment,
      respectively. Increased [18F]FLT uptake after capecitabine followed by extinction
      of uptake correlated strongly with tumor growth inhibition (rho = -0.81, P =
      0.02). The effects of these combinations were synergistic in vitro A synergy for
      sequential capecitabine and trifluridine/tipiracil was found only in mouse
      xenograft models showing increased [18F]FLT uptake after capecitabine. Our
      results suggest that the sequential combination of capecitabine and
      trifluridine/tipiracil is synergistic in tumors with an activated salvage pathway
      after capecitabine treatment in mice, and [18F]FLT PET imaging may predict the
      response to capecitabine and the synergistic antitumor efficacy of a sequential
      combination of capecitabine and trifluridine/tipiracil. Cancer Res; 77(24); 7120
      30. (c)2017 AACR.

PMID- 29055020
TI  - Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of
      Uterine Leiomyoma.
AB  - Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with
      distinctive genetic alterations. Here, we report the elucidation of the
      biological characteristics of the two most prevalent uterine leiomyoma subtypes,
      MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas.
      Because each tumor carries only one genetic alteration, both subtypes are
      considered to be monoclonal. Approximately 90% of cells in HMGA2-uterine
      leiomyoma were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast,
      MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor
      associated fibroblasts (TAF). Paradoxically, TAF carried no mutations in MED12,
      suggesting an interaction between SMC and TAF to coordinate their growth. The
      higher amount of extracellular matrix in MED12-LM than HMGA2-LM was partially due
      to the high concentration of collagen-producing TAF. SMC growth in a xenograft
      assay was driven by progesterone in both uterine leiomyoma subtypes. In contrast,
      TAF in MED12-LM proliferated in response to estradiol, whereas progesterone had
      no effect. The high concentration of estrogen-responsive TAF in MED12-LM explains
      the inconsistent discoveries between in vivo and in vitro studies on the
      mitogenic effect of estrogen and raises questions regarding the accuracy of
      previous studies utilizing MED12-LM cell culture. In addition, the differential
      effects of estradiol and progesterone on these uterine leiomyoma subtypes
      emphasize the importance of subtypes and genotypes in designing nonsurgical
      therapeutic strategies for uterine leiomyoma. Cancer Res; 77(24); 6891-901.
      (c)2017 AACR.

PMID- 29055021
TI  - MEERCAT: Multiplexed Efficient Cell Free Expression of Recombinant QconCATs For
      Large Scale Absolute Proteome Quantification.
AB  - A major challenge in proteomics is the absolute accurate quantification of large
      numbers of proteins. QconCATs, artificial proteins that are concatenations of
      multiple standard peptides, are well established as an efficient means to
      generate standards for proteome quantification. Previously, QconCATs have been
      expressed in bacteria, but we now describe QconCAT expression in a robust, cell
      free system. The new expression approach rescues QconCATs that previously were
      unable to be expressed in bacteria and can reduce the incidence of proteolytic
      damage to QconCATs. Moreover, it is possible to cosynthesize QconCATs in a highly
      multiplexed translation reaction, coexpressing tens or hundreds of QconCATs
      simultaneously. By obviating bacterial culture and through the gain of high level
      multiplexing, it is now possible to generate tens of thousands of standard
      peptides in a matter of weeks, rendering absolute quantification of a complex
      proteome highly achievable in a reproducible, broadly deployable system.

PMID- 29055022
TI  - The addition of a developmental factor, unc-62, to already long-lived worms
      increases lifespan and healthspan.
AB  - Aging is a complex trait that is affected by multiple genetic pathways. A
      relatively unexplored approach is to manipulate multiple independent aging
      pathways simultaneously in order to observe their cumulative effect on lifespan.
      Here, we report the phenotypic characterization of a strain with changes in five
      aging pathways: (1) mitochondrial reactive oxygen species (ROS) production, (2)
      innate immunity, (3) stress response, (4) metabolic control and (5) developmental
      regulation in old age. The quintuply modified strain has a lifespan that is 160%
      longer than the transgenic control strain. Additionally, the quintuply modified
      strain maintains several physiological markers of aging for a longer time than
      the transgenic control. Our results support a modular approach as a general
      scheme to study how multiple pathways interact to achieve extreme longevity.

PMID- 29055023
TI  - Using Physician-Level Emergency Department Utilization Reports to Address
      Avoidable Visits by Patients Managed by Pediatric Specialists.
AB  - OBJECTIVES: Emergency department (ED) utilization is a major driver of cost.
      Specialist physicians have an important role in addressing ED utilization,
      especially at tertiary medical centers that treat highly specialized patients. We
      analyzed if reporting of ED utilization to pediatric specialist physicians can
      decrease ED visits. METHODS: Physicians within pediatric neurology, hematology
      and oncology, infectious diseases, and pulmonary divisions received their ED use
      reports. By using control charts, we examined if this intervention decreased the
      rate of ED utilization. RESULTS: Overall, for the 4 divisions, specialty-related
      ED utilization decreased significantly during all hours, weekdays, and office
      hours. This was in the setting of ED utilization increasing for all diagnoses ED
      visits. Pediatric ED volume did not change during the study period. CONCLUSIONS:
      Physician-level reporting of ED utilization was associated with a reduction in ED
      use by patients managed by our pediatric specialists.

PMID- 29055024
TI  - Serum Lipid, Vitamin D Levels, and Obesity in Perimenopausal and Postmenopausal
      Women in Non-Manual Employment.
AB  - BACKGROUND Increasing age, increased body mass index (BMI), and abnormal lipid
      profiles contribute to an increased risk of vitamin D deficiency. Women who have
      a perimenopausal and postmenopausal reduction in estrogen levels are a high-risk
      group for vitamin D deficiency. The aims of this study were to compare the serum
      vitamin D levels, lipid profile, and BMI between perimenopausal and
      postmenopausal women in non-manual employment, and to determine whether there
      were any interdependent factors. MATERIAL AND METHODS Three hundred women in non
      manual employment, aged between 44-66 years, were divided into three groups:
      early perimenopausal; late perimenopausal; and postmenopausal. Laboratory tests
      included measurement of serum lipid profiles and vitamin D levels, the BMI, waist
      hip ratio (WHR) and body fat were measured. Statistical analysis included F-test
      analysis of variance and the least significance difference (LSD) test was used
      for multiple comparisons. RESULTS For the 300 women who were in non-manual
      employment, and in the early and late perimenopausal and postmenopausal periods,
      serum vitamin D levels were reduced (mean 16.8+/-8.7 ng/mL); 29% of women had
      abdominal obesity; 41% had excessive body fat accumulation; and 56% had an
      increased body mass index (BMI) (>25 kg/m2) with raised total cholesterol, low
      density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL), and
      total cholesterol/HDL ratios (p<0.05). CONCLUSIONS The findings of this study
      showed that in perimenopausal and postmenopausal women in non-manual employment,
      serum vitamin D levels were associated with serum lipid profile and degrees of
      obesity.

PMID- 29055025
TI  - Contribution of equilibrative nucleoside transporter(s) to intestinal basolateral
      and apical transports of anticancer trifluridine.
AB  - Trifluridine (FTD) exhibits anticancer activities after its oral administration
      despite its hydrophilic nature. It was previously reported that concentrative
      nucleoside transporter (CNT) 1 mediates the apical uptake of FTD in human small
      intestinal epithelial cells (HIECs). In the present study, FTD was also
      identified as a substrate for equilibrative nucleoside transporter (ENT) 1 and
      ENT2 in transporter gene-transfected cells. An immunocytochemical analysis
      revealed that ENT1 was expressed at the basolateral and apical membranes of
      HIECs. Cellular accumulation increased in the presence of S-(4-nitrobenzyl)-6
      thioinosine (NBMPR), an ENT selective inhibitor. Cytotoxicity in HIEC monolayers
      at low FTD concentrations was increased by NBMPR, and this may have been due to
      inhibition of the ENT-mediated basolateral transport of FTD by NBMPR. These
      results suggest that ENTs reduce the intestinal cytotoxicity of FTD by
      facilitating its basolateral efflux. On the other hand, the intracellular
      accumulation and cytotoxicity of FTD in HIECs were decreased at higher
      concentrations of FTD by NBMPR, and this may have been due to the NBMPR
      inhibition of the apical uptake of FTD, which has been suggested to be mediated
      by CNTs and ENTs. In conclusion, ENTs were responsible for intestinal
      transepithelial permeation by mediating the basolateral efflux of FTD after its
      uptake by CNT1 from the apical side, resulting in decreases in its intracellular
      accumulation and intestinal toxicity in humans. Equilibrative nucleoside
      transporters may also partially contribute to the low-affinity uptake of FTD
      across the apical membrane along with high-affinity CNT1.

PMID- 29055026
TI  - Malaria, Epstein-Barr virus, vitamin A and Burkitt's lymphoma.

PMID- 29055028
TI  - Malaria, Epstein-Barr virus, vitamin A and Burkitt's lymphoma: Response to Joob
      and Wiwanitkit.

PMID- 29055027
TI  - Pharmacological and gene regulation properties point to the SlHAK5 K+ transporter
      as a system for high-affinity Cs+ uptake in tomato plants.
AB  - Potassium (K+ ) and cesium (Cs+ ) are chemically similar but while K+ is an
      essential nutrient, Cs+ can be toxic for living organisms, plants included. Two
      different situations could lead to problems derived from the presence of Cs+ in
      agricultural systems: (1) presence of Cs+ at high concentrations that could
      produce toxic effects on plants, (2) presence of micromolar concentrations of
      radiocesium, which can be accumulated in the plant and affect animal and human
      health through the food chain. While K+ uptake has been well described in tomato
      plants, information on molecular mechanisms involved in Cs+ accumulation in this
      species is absent. Here, we show that in tomato plants, high concentrations of
      Cs+ produce deficiency of K+ but do not induce high-affinity K+ uptake or the
      gene encoding the high-affinity K+ transporter SlHAK5. At these concentrations,
      Cs+ uptake takes place through a Ca2+ -sensitive pathway, probably a non
      selective cation channel. At micromolar concentrations, Cs+ is accumulated by a
      high-affinity uptake system upregulated in K+ -starved plants. This high-affinity
      Cs+ uptake shares features with high-affinity K+ uptake. It is sensitive to NH4+
      and insensitive to Ba2+ and Ca2+ and its presence parallels the pattern of SlHAK5
      expression. Moreover, blockers of reactive oxygen species and ethylene action
      repress SlHAK5 and negatively regulate both high-affinity K+ and Cs+ uptake.
      Thus, we propose that SlHAK5 contributes to Cs+ uptake from micromolar
      concentrations in tomato plants and can constitute a pathway for radiocesium
      transfer from contaminated areas to the food chain.

PMID- 29055029
TI  - Cancer incidence in adults living in the vicinity of nuclear power plants in
      France, based on data from the French Network of Cancer Registries.
AB  - Nuclear power plants (NPPs) release toxic emissions into the environment that may
      affect neighboring populations. This ecologic study was designed to investigate
      the possibility of an excess incidence of cancer in the vicinity of French NPPs
      by examining the incidence by municipality of 12 types of cancer in the
      population aged 15 years and older during the 1995-2011 period. Population
      exposure to pollution was estimated on the basis of distance from towns of
      residence to the NPP. Using regression models, we assessed the risk of cancer in
      a 20-km zone around NPPs and observed an excess incidence of bladder cancer
      (Relative Risk (RR), 95% Credibility Interval (95% CI)) in men and women (RRmen 
      = 1.08; 95% CI: 1.00, 1.17 and RRwomen  = 1.19; 95% CI: 1.02, 1.39). Women living
      within the 20-km proximity areas had a significantly reduced risk of thyroid
      cancer (RRwomen  = 0.86; 95% CI: 0.77, 0.96). No excess risk of hematologic
      malignancies in either sex was seen. The higher than expected incidence of
      bladder cancer may be due to an excess incidence localized around the Flamanville
      NPP and the nearby La Hague nuclear waste treatment center, which is a source of
      chemical contaminants, many (including arsenic) of them known risk factors for
      bladder cancer. Differences in medical practices could explain the reduced risk
      of thyroid cancer. In this first study of adults living near NPPs in France,
      cancer incidence is significantly higher than in the references populations for
      one of the cancer types studied: bladder cancer.

PMID- 29055030
TI  - Identification of absorbed constituents and in vivo metabolites in rats after
      oral administration of Physalis alkekengi var. franchetii by ultra-high-pressure
      liquid chromatography quadrupole time-of-flight mass spectrometry.
AB  - The calyces of Physalis alkekengi var. franchetii (Chinese Lantern, JDL) are well
      known as traditional Chinese medicine owing to its various therapeutic effects.
      However, the bioactive constituents responsible for the pharmacological effects
      of JDL and their metabolites in vivo are still unclear to date. In this paper, an
      ultra-high-pressure liquid chromatography coupled with quadrupole time-of-flight
      mass spectrometry (UHPLC/Q-TOF-MS/MS) method was established to identify absorbed
      constituents and in vivo metabolites in rat biological fluids after oral
      administration of JDL. Based on the proposed strategy, 33 compounds were observed
      in dosed rat biosamples. Twelve of 33 compounds were indicated as prototype
      components of JDL, and 21 compounds were predicted to be metabolites of JDL.
      Finally, the metabolic pathways were proposed, which were glucuronidation,
      sulfation, methylation and dehydroxylation for flavonoid constituents and
      sulfonation and hydroxylation for physalin consitituents. This is the first
      systematic study on the absorbed constituents and metabolic profiling of JDL and
      will provide a useful template for screening and characterizing the ingredients
      and metabolites of traditional Chinese medicine.

PMID- 29055031
TI  - Impact of gender-neutral or girls-only vaccination against human papillomavirus
      Results of a community-randomized clinical trial (I).
AB  - Human papillomavirus (HPV) vaccine is efficacious but the real-life effectiveness
      of gender-neutral and girls-only vaccination strategies is unknown. We report a
      community-randomized trial on the protective effectiveness [(PE) = vaccine
      efficacy (VE) + herd effect (HE)] of the two strategies among females in
      virtually HPV vaccination naive population. We randomized 33 Finnish communities
      into Arm A) gender-neutral vaccination with AS04-adjuvanted HPV16/18 vaccine (11
      communities), Arm B) HPV vaccination of girls and hepatitis B-virus (HBV)
      vaccination of boys (11 communities) or Arm C) gender-neutral HBV vaccination (11
      communities). All resident 39,420 females and 40,852 males born 1992-95 were
      invited in 2007-09. Virtually all (99%) 12- to 15-year-old participating males
      (11,662) and females (20,513) received three doses resulting in uniform 20-30%
      male and 50% female vaccination coverage by birth cohort. Four years later (2010
      14) 11,396 cervicovaginal samples obtained from 18.5 year-old women were tested
      for HPV DNA, and prevalence of cervical HPV infections by trial arm and birth
      cohort was the main outcome measure. VEs against HPV16/18 varied between 89.2%
      and 95.2% across birth cohorts in arms A and B. The VEs against non-vaccine types
      consistent with cross-protection were highest in those born 1994-95 for HPV45
      (VEA 82.8%; VEB 86.1%) and for HPV31 (VEA 77.6%, VEB 84.6%). The HEs in the non
      HPV-vaccinated were statistically significant in those born 1994-95 for HPV18
      (HEA 51.0%; 95% CI 8.3-73.8, HEB 47.2%; 6.5-70.2) and for HPV31/33 in arm A (HEA
      53.7%; 22.1-72.5). For HPV16 and 45 no significant herd effects were detected. PE
      estimates against HPV16/18 were similar by both strategies (PEA 58.1%; 45.1-69.4;
      PEB 55.7%; 42.9-66.6). PE estimates against HPV31/33 were higher by the gender
      neutral vaccination (PEA 60.5%; 43.6-73.4; PEB 44.5%; 24.9-60.6). In conclusion,
      while gender-neutral strategy enhanced the effectiveness of HPV vaccination for
      cross-protected HPV types with low to moderate coverage, high coverage in males
      appears to be key to providing a substantial public health benefit also to
      unvaccinated females. Trial registration www.clinicaltrials.gov.com NCT000534638.

PMID- 29055032
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13880/full. Nuclear hormone
      receptors are one of the eight major pharmacological targets into which the Guide
      is divided, with the others being: G protein-coupled receptors, ligand-gated ion
      channels, voltage-gated ion channels, other ion channels, catalytic receptors,
      enzymes and transporters. These are presented with nomenclature guidance and
      summary information on the best available pharmacological tools, alongside key
      references and suggestions for further reading. The landscape format of the
      Concise Guide is designed to facilitate comparison of related targets from
      material contemporary to mid-2017, and supersedes data presented in the 2015/16
      and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is
      produced in close conjunction with the Nomenclature Committee of the Union of
      Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR
      classification and nomenclature for human drug targets, where appropriate. (c)
      2015 The British Pharmacological Society.

PMID- 29055033
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage-gated ion channels.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13884/full. Voltage-gated ion
      channels are one of the eight major pharmacological targets into which the Guide
      is divided, with the others being: G protein-coupled receptors, ligand-gated ion
      channels, other ion channels, nuclear hormone receptors, catalytic receptors,
      enzymes and transporters. These are presented with nomenclature guidance and
      summary information on the best available pharmacological tools, alongside key
      references and suggestions for further reading. The landscape format of the
      Concise Guide is designed to facilitate comparison of related targets from
      material contemporary to mid-2017, and supersedes data presented in the 2015/16
      and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is
      produced in close conjunction with the Nomenclature Committee of the Union of
      Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR
      classification and nomenclature for human drug targets, where appropriate.

PMID- 29055034
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Enzymes.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13877/full. Enzymes are one of the
      eight major pharmacological targets into which the Guide is divided, with the
      others being: G protein-coupled receptors, ligand-gated ion channels, voltage
      gated ion channels, other ion channels, nuclear hormone receptors, catalytic
      receptors and transporters. These are presented with nomenclature guidance and
      summary information on the best available pharmacological tools, alongside key
      references and suggestions for further reading. The landscape format of the
      Concise Guide is designed to facilitate comparison of related targets from
      material contemporary to mid-2017, and supersedes data presented in the 2015/16
      and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is
      produced in close conjunction with the Nomenclature Committee of the Union of
      Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR
      classification and nomenclature for human drug targets, where appropriate.

PMID- 29055035
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Transporters.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13883/full. Transporters are one
      of the eight major pharmacological targets into which the Guide is divided, with
      the others being: G protein-coupled receptors, ligand-gated ion channels, voltage
      gated ion channels, other ion channels, nuclear hormone receptors, catalytic
      receptors and enzymes. These are presented with nomenclature guidance and summary
      information on the best available pharmacological tools, alongside key references
      and suggestions for further reading. The landscape format of the Concise Guide is
      designed to facilitate comparison of related targets from material contemporary
      to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise
      Guides and previous Guides to Receptors and Channels. It is produced in close
      conjunction with the Nomenclature Committee of the Union of Basic and Clinical
      Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and
      nomenclature for human drug targets, where appropriate.

PMID- 29055036
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Catalytic receptors.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13876/full. Catalytic receptors
      are one of the eight major pharmacological targets into which the Guide is
      divided, with the others being: G protein-coupled receptors, ligand-gated ion
      channels, voltage-gated ion channels, other ion channels, nuclear hormone
      receptors, enzymes and transporters. These are presented with nomenclature
      guidance and summary information on the best available pharmacological tools,
      alongside key references and suggestions for further reading. The landscape
      format of the Concise Guide is designed to facilitate comparison of related
      targets from material contemporary to mid-2017, and supersedes data presented in
      the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and
      Channels. It is produced in close conjunction with the Nomenclature Committee of
      the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing
      official IUPHAR classification and nomenclature for human drug targets, where
      appropriate.

PMID- 29055038
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Ligand-gated ion channels.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13879/full. Ligand-gated ion
      channels are one of the eight major pharmacological targets into which the Guide
      is divided, with the others being: G protein-coupled receptors, voltage-gated ion
      channels, other ion channels, nuclear hormone receptors, catalytic receptors,
      enzymes and transporters. These are presented with nomenclature guidance and
      summary information on the best available pharmacological tools, alongside key
      references and suggestions for further reading. The landscape format of the
      Concise Guide is designed to facilitate comparison of related targets from
      material contemporary to mid-2017, and supersedes data presented in the 2015/16
      and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is
      produced in close conjunction with the Nomenclature Committee of the Union of
      Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR
      classification and nomenclature for human drug targets, where appropriate.

PMID- 29055039
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Other ion channels.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13881/full. Other ion channels are
      one of the eight major pharmacological targets into which the Guide is divided,
      with the others being: G protein-coupled receptors, ligand-gated ion channels,
      voltage-gated ion channels, nuclear hormone receptors, catalytic receptors,
      enzymes and transporters. These are presented with nomenclature guidance and
      summary information on the best available pharmacological tools, alongside key
      references and suggestions for further reading. The landscape format of the
      Concise Guide is designed to facilitate comparison of related targets from
      material contemporary to mid-2017, and supersedes data presented in the 2015/16
      and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is
      produced in close conjunction with the Nomenclature Committee of the Union of
      Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR
      classification and nomenclature for human drug targets, where appropriate.

PMID- 29055040
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein-coupled receptors.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key
      properties of nearly 1800 human drug targets with an emphasis on selective
      pharmacology (where available), plus links to an open access knowledgebase of
      drug targets and their ligands (www.guidetopharmacology.org), which provides more
      detailed views of target and ligand properties. Although the Concise Guide
      represents approximately 400 pages, the material presented is substantially
      reduced compared to information and links presented on the website. It provides a
      permanent, citable, point-in-time record that will survive database updates. The
      full contents of this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13878/full. G protein-coupled
      receptors are one of the eight major pharmacological targets into which the Guide
      is divided, with the others being: ligand-gated ion channels, voltage-gated ion
      channels, other ion channels, nuclear hormone receptors, catalytic receptors,
      enzymes and transporters. These are presented with nomenclature guidance and
      summary information on the best available pharmacological tools, alongside key
      references and suggestions for further reading. The landscape format of the
      Concise Guide is designed to facilitate comparison of related targets from
      material contemporary to mid-2017, and supersedes data presented in the 2015/16
      and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is
      produced in close conjunction with the Nomenclature Committee of the Union of
      Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR
      classification and nomenclature for human drug targets, where appropriate.

PMID- 29055037
TI  - THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview.
AB  - The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial
      publications. This version provides concise overviews of the key properties of
      nearly 1800 human drug targets with an emphasis on selective pharmacology (where
      available), plus links to an open access knowledgebase of drug targets and their
      ligands (www.guidetopharmacology.org), which provides more detailed views of
      target and ligand properties. Although the Concise Guide represents approximately
      400 pages, the material presented is substantially reduced compared to
      information and links presented on the website. It provides a permanent, citable,
      point-in-time record that will survive database updates. The full contents of
      this section can be found at
      http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this
      overview, in which are identified 'Other protein targets' which fall outside of
      the subsequent categorisation, there are eight areas of focus: G protein-coupled
      receptors, ligand-gated ion channels, voltage-gated ion channels, other ion
      channels, nuclear hormone receptors, catalytic receptors, enzymes and
      transporters. These are presented with nomenclature guidance and summary
      information on the best available pharmacological tools, alongside key references
      and suggestions for further reading. The landscape format of the Concise Guide is
      designed to facilitate comparison of related targets from material contemporary
      to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise
      Guides and previous Guides to Receptors and Channels. It is produced in close
      conjunction with the Nomenclature Committee of the Union of Basic and Clinical
      Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and
      nomenclature for human drug targets, where appropriate.

PMID- 29055041
TI  - The possible clinical impact of risperidone on P-glycoprotein-mediated transport
      of tacrolimus: A case report and in vitro study.
AB  - The authors encountered the case of an 8-fold increase in the concentration/dose
      (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole
      (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The
      interaction observed was much greater than expected and the patient had also been
      treated with oral risperidone (RSP). It was hypothesized that cytochrome P450
      (CYP)3A inhibition of the small intestine by voriconazole and P-glycoprotein (P
      gp) inhibition of the small intestine by risperidone exerted a synergistic effect
      on the bioavailability of tacrolimus. The aim of the present study was to
      evaluate the effect of risperidone on the P-gp-mediated transport of tacrolimus.
      The transcellular transport of P-gp substrates was examined in Caco-2 and P-gp
      expressing renal epithelial LLC-GA5-COL150 cells. In Caco-2 cells, the apical
      basal (A-B) transport of rhodamine123 (Rh123) after a 120 min incubation was
      increased by 47.1%, whereas that in the B-A direction was decreased by 61.7% in
      the presence of risperidone (100 MUm). These results indicate that risperidone
      showed an inhibitory effect on the P-gp-mediated transport of Rh123. In LLC-GA5
      COL150 cells, the A-B transport of tacrolimus after 120 min incubation was
      increased by 21.7% in the presence of risperidone (100 MUm), whereas that in the
      B-A direction was decreased by 10.7%. These results suggest that risperidone was
      at least partly involved in the mechanism of the marked increase in the C/D ratio
      of tacrolimus. This case report provides new insights into the diversity of drug
      interactions of tacrolimus triggered by the combination of two concomitant drugs.

PMID- 29055042
TI  - Polygonal current models for polycyclic aromatic hydrocarbons and graphene sheets
      of various shapes.
AB  - Assuming that graphene is an "infinite alternant" polycyclic aromatic hydrocarbon
      resulting from tessellation of a surface by only six-membered carbon rings,
      planar fragments of various size and shape (hexagon, triangle, rectangle, and
      rhombus) have been considered to investigate their response to a magnetic field
      applied perpendicularly. Allowing for simple polygonal current models, the
      diatropicity of a series of polycyclic textures has been reliably determined by
      comparing quantitative indicators, the pi-electron contribution to IB , the
      magnetic field-induced current susceptibility of the peripheral circuit, to xi?
      and to sigma?(CM)=-NICS?(CM), respectively the out-of-plane components of the
      magnetizability tensor and of the magnetic shielding tensor at the center of
      mass. Extended numerical tests and the analysis based on the polygonal model
      demonstrate that (i) xi? and sigma?(CM) yield inadequate and sometimes erroneous
      measures of diatropicity, as they are heavily flawed by spurious geometrical
      factors, (ii) IB values computed by simple polygonal models are valid
      quantitative indicators of aromaticity on the magnetic criterion, preferable to
      others presently available, whenever current susceptibility cannot be calculated
      ab initio as a flux integral, (iii) the hexagonal shape is the most effective to
      maximize the strength of pi-electron currents over the molecular perimeter, (iv)
      the edge current strength of triangular and rhombic graphene fragments is usually
      much smaller than that of hexagonal ones, (v) doping by boron and nitrogen nuclei
      can regulate and even inhibit peripheral ring currents, (vi) only for very large
      rectangular fragments can substantial current strengths be expected. (c) 2017
      Wiley Periodicals, Inc.

PMID- 29055043
TI  - Diffusional conductance to CO2 is the key limitation to photosynthesis in salt
      stressed leaves of rice (Oryza sativa).
AB  - Salinity significantly limits leaf photosynthesis but the factors causing the
      limitation in salt-stressed leaves remain unclear. In the present work,
      photosynthetic and biochemical traits were investigated in four rice genotypes
      under two NaCl concentration (0 and 150 mM) to assess the stomatal, mesophyll and
      biochemical contributions to reduced photosynthetic rate (A) in salt-stressed
      leaves. Our results indicated that salinity led to a decrease in A, leaf osmotic
      potential, electron transport rate and CO2 concentrations in the chloroplasts (Cc
      ) of rice leaves. Decreased A in salt-stressed leaves was mainly attributable to
      low Cc , which was determined by stomatal and mesophyll conductance. The
      increased stomatal limitation was mainly related to the low leaf osmotic
      potential caused by soil salinity. However, the increased mesophyll limitation in
      salt-stressed leaves was related to both osmotic stress and ion stress. These
      findings highlight the importance of considering mesophyll conductance when
      developing salinity-tolerant rice cultivars.

PMID- 29055044
TI  - Anti-glypican-1 antibody-drug conjugate exhibits potent preclinical antitumor
      activity against glypican-1 positive uterine cervical cancer.
AB  - Glypican-1 (GPC1) is highly expressed in solid tumors, especially squamous cell
      carcinomas (SCCs), and is thought to be associated with disease progression. We
      explored the use of a GPC1-targeted antibody-drug conjugate (ADC) as a novel
      treatment for uterine cervical cancer. On immunohistochemical staining, high
      expression levels of GPC1 were detected in about 50% of uterine cervical cancer
      tissues and also in a tumor that had relapsed after chemoradiotherapy. Novel anti
      GPC1 monoclonal antibodies were developed, and clone 01a033 was selected as the
      best antibody for targeted delivery of the cytotoxic agent monomethyl auristatin
      F (MMAF) into GPC1-positive cells. The anti-GPC1 antibody was conjugated with
      MMAF. On flow cytometry, HeLa and ME180 cervical cancer cells highly expressed
      GPC1, however, RMG-I ovarian clear cell cancer cell line showed weak expression.
      The GPC1-ADC was rapidly internalized into GPC1-expressing cells in vitro and was
      potently cytotoxic to cancer cells highly expressing GPC1. There were no
      inhibitory effects on cancer cells with low expression of GPC1. In a murine
      xenograft model, GPC1-ADC also had significant and potent tumor growth
      inhibition. GPC1-ADC-mediated G2/M phase cell cycle arrest was detected,
      indicating that the dominant antitumor effect in vivo was MMAF-mediated. The
      toxicity of GPC-ADC was tolerable within the therapeutic dose range in mice. Our
      data showed that GPC1-ADC has potential as a promising therapy for uterine
      cervical cancer.

PMID- 29055045
TI  - Diagnostic relevance of IgE sensitization profiles to eight recombinant Phleum
      pratense molecules.
AB  - BACKGROUND: Grass pollen-related seasonal allergic rhinoconjunctivitis (SARg) is
      clinically heterogeneous in severity, comorbidities, and response to treatment.
      The component-resolved diagnostics disclosed also a high heterogeneity at
      molecular level. Our study aimed at analyzing the characteristics of the IgE
      sensitization to Phleum pratense molecules and investigating the diagnostic
      relevance of such molecules in childhood. METHODS: We examined 1120 children (age
      4-18 years) with SARg. Standardized questionnaires on atopy were acquired through
      informatics platform (AllergyCARDTM). Skin prick tests were performed with pollen
      extracts. Serum IgE to airborne allergens and eight P. pratense molecules (rPhl p
      1, rPhl p 2, rPhl p 4, rPhl p 5b, rPhl p 6, rPhl p 7, rPhl p 11, rPhl p 12) were
      tested by ImmunoCAP FEIA. RESULTS: The analysis of IgE responses against eight P.
      pratense molecules showed 87 profiles. According to the number of molecules
      recognized by IgE, the more complex profiles were characterized by higher serum
      total IgE, higher grass-specific serum IgE, and higher number and degree of
      sensitization to pollens. The most frequent IgE sensitization profile was the
      monomolecular Phl p 1. Sensitization to Phl p 7 was a reliable biomarker of
      asthma, whereas Phl p 12 of oral allergy syndrome. Sensitization to Phl p 7 was
      associated with a higher severity of SARg, and complex profiles were associated
      with longer disease duration. CONCLUSIONS: In a large pediatric population, the
      complexity of IgE sensitization profiles against P. pratense molecules is related
      to high atopic features although useless for predicting the clinical severity.
      The detection of serum IgE to Phl p 1, Phl p 7, and Phl p 12 can be used as
      clinical biomarkers of SARg and comorbidities. Further studies in different areas
      are required to test the impact of different IgE molecular profiles on AIT
      response.

PMID- 29055046
TI  - An assessment of depression, psychosocial factors, and resilience among women
      seeking prenatal care at an urban community health center.
AB  - OBJECTIVE: To describe the relationship between resilience and mental health and
      psychosocial characteristics in the prenatal period. METHODS: A prospective
      cohort pilot study was conducted among English-speaking women aged 18 years or
      older with singleton pregnancies of at least 20 weeks' duration who received
      prenatal care at an urban community health center in the USA between March and
      October 2014. Surveys were administered and a retrospective chart review was
      conducted. Resilience and depression were measured using validated scales and
      anxiety was self-reported. Univariate and bivariate analyses were performed.
      RESULTS: Thirty women participated. The median resilience score was 82.0
      (interquartile range [IQR] 74.0-92.0). Median resilience scores were
      significantly lower among women with a history of depression (73.0 [IQR 66.0
      81.0]) than among those without a history (85.0 [IQR 79.0-92.0]; P=0.007). A
      history of using medication for anxiety, depression, or insomnia before pregnancy
      was also associated with lower resilience (median 74.0 [IQR 64.5-80.0] vs 83.5
      [IQR 79.0-92.0]; P=0.029). Neither anxiety nor substance use was associated with
      resilience. Higher resilience was associated with religious affiliation and
      having adequate financial resources (both P<0.05). CONCLUSION: Depression
      history, prior medication use, religious affiliation, and financial security
      affect resilience in pregnancy. These data inform a strengths-based approach to
      prenatal care and future research endeavors.

PMID- 29055047
TI  - Species-specific role of gene-adjacent retroelements in human and mouse gastric
      carcinogenesis.
AB  - Helicobacter pylori (HP) infection promotes the recruitment of bone marrow stem
      cells into chronic gastritis lesions. Some of these marrow stem cells can
      differentiate into gastric epithelial cells and neoplastic cells. We propose that
      HP-associated methylation could stabilize trans-differentiation of marrow-derived
      stem cells and that an unstable methylation status is associated with a risk of
      gastric cancer. Pathobiologic behavior of experimental mouse gastric cancer is
      mild compared to invasive and metastatic human gastric cancer. Differences in
      epigenetic stabilization of adult cell phenotypes between humans and mice could
      provide a foundation to explore the development of invasive and metastatic
      gastric cancer. Retroelements are highly repetitive sequences that play an
      essential role in the generation of species diversity. In this review, we
      analyzed retroelements adjacent to human and mouse housekeeping genes and
      proposed a possible epigenetic mechanism for HP-associated carcinogenesis.

PMID- 29055048
TI  - Adolescent obesity and adult male breast cancer in a cohort of 1,382,093 men.
AB  - Male breast cancer (MBC) accounts for 1% of all breast cancer. Adult obesity and
      tallness are risk factors for MBC, but the role of adolescent fatness is largely
      unknown. We aimed to assess the association between body mass index (BMI) in
      adolescence and the incidence of MBC in a large cohort of 16- to 19-year-old
      Israeli males. 1,382,093 Jewish Israeli males aged 16-19 who underwent
      anthropometric measurements, a general intelligence test (GIT) and other
      examinations during 1967-2011, were followed up to December 31, 2012 for MBC
      incidence. Cox proportional hazards models assessed the association between
      adolescent BMI (as WHO BMI categories and as age-specific CDC percentiles) and
      time to MBC diagnosis, adjusting for sociodemographic covariates. Of 100 MBC
      cases diagnosed during 29,386,233 person-years of follow-up, 97 were included in
      multivariable analyses. Compared to "healthy" BMI (18.5-24.9 kg/m2 ) and adjusted
      for year of birth, country of origin and GIT score, higher adolescent BMI was
      associated with higher MBC risk: hazard ratio (HR) = 2.01 (95% confidence
      interval [CI] 1.14-3.55, p = 0.015) in overweight (25.0 <= BMI < 30.0 kg/m2 )
      adolescents; and HR = 4.97 (95%CI 2.14-11.53, p = 0.0002) in obese (BMI >= 30.0
      kg/m2 ) adolescents. When CDC age-specific BMI percentiles were assessed results
      were similar and statistically significant for obesity. In addition, low (vs.
      high) GIT score (HR = 4.76, 95%CI 1.96-12.50, p = 0.001) and European (vs. west
      Asian) origin (HR = 1.99, 95%CI 1.19-3.34, p = 0.009) were independent predictors
      of MBC. Measured adolescent overweight and obesity are associated with increased
      risk of MBC, suggesting a modifiable risk factor potentially allowing for early
      intervention. The novel association with cognitive function should be further
      explored.

PMID- 29055049
TI  - PAX9 regulates squamous cell differentiation and carcinogenesis in the oro
      oesophageal epithelium.
AB  - PAX9 is a transcription factor of the PAX family characterized by a DNA-binding
      paired domain. Previous studies have suggested a potential role of PAX9 in
      squamous cell differentiation and carcinogenesis of the oro-oesophageal
      epithelium. However, its functional roles in differentiation and carcinogenesis
      remain unclear. In this study, Pax9 deficiency in mouse oesophagus promoted cell
      proliferation, delayed cell differentiation, and altered the global gene
      expression profile. Ethanol exposure downregulated PAX9 expression in human
      oesophageal epithelial cells in vitro and mouse forestomach and tongue in vivo.
      We further showed that PAX9 was downregulated in human oro-oesophageal squamous
      cell carcinoma (OESCC), and its downregulation was associated with alcohol
      drinking and promoter hypermethylation. Moreover, ad libitum feeding with a
      liquid diet containing ethanol for 40 weeks or Pax9 deficiency promoted N
      nitrosomethylbenzylamine-induced squamous cell carcinogenesis in mouse tongue,
      oesophagus, and forestomach. In conclusion, PAX9 regulates squamous cell
      differentiation in the oro-oesophageal epithelium. Alcohol drinking and promoter
      hypermethylation are associated with PAX9 silencing in human OESCC. PAX9
      downregulation may contribute to alcohol-associated oro-oesophageal squamous cell
      carcinogenesis. Copyright (c) 2017 Pathological Society of Great Britain and
      Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29055050
TI  - An evolutionary framework outlining the integration of individual social and
      spatial ecology.
AB  - Behaviour is the interface between an organism and its environment, and
      behavioural plasticity is important for organisms to cope with environmental
      change. Social behaviour is particularly important because sociality is a dynamic
      process, where environmental variation influences group dynamics and social
      plasticity can mediate resource acquisition. Heterogeneity in the ecological
      environment can therefore influence the social environment. The combination of
      the ecological and social environments may be interpreted collectively as the
      "socioecological environment," which could explain variation in fitness. Our
      objective was to outline a framework through which individual social and spatial
      phenotypes can be integrated and interpreted as phenotypes that covary as a
      function of changes in the socioecological environment. We propose the
      socioecological environment is composed of individual behavioural traits,
      including sociality and habitat selection, both of which are repeatable,
      potentially heritable and may reflect animal personality traits. We also
      highlight how ecological and social niche theory can be applied to the
      socioecological environment framework, where individuals occupy different
      socioecological niches. Individual sociality and habitat selection are also
      density-dependent, and theory predicts that density-dependent traits should
      affect reproduction, survival, and therefore fitness and population dynamics. We
      then illustrate the proximate links between sociality, habitat selection and
      fitness as well as the ultimate, and possibly adaptive, consequences associated
      with changes in population density. The ecological, evolutionary and applied
      implications of our proposed socioecological environment framework are broad and
      changes in density could influence individual fitness and population dynamics.
      For instance, human-induced environmental changes can influence population
      density, which can affect the distribution of social and spatial phenotypes
      within a population. In summary, we outline a conceptual framework that
      incorporates individual social and spatial behavioural traits with fitness and we
      highlight a range of ecological and evolutionary processes that are likely
      associated with the socioecological environment.

PMID- 29055052
TI  - Pregnancy before recurrent pregnancy loss more often complicated by post-term
      birth and perinatal death.
AB  - INTRODUCTION: The cause of recurrent pregnancy loss often remains unknown.
      Possibly, pathophysiological pathways are shared with other pregnancy
      complications. MATERIAL AND METHODS: All women with secondary recurrent pregnancy
      loss (SRPL) visiting Leiden University Medical Center (January 2000-2015) were
      included in this retrospective cohort to assess whether women with SRPL have a
      more complicated first pregnancy compared with control women. SRPL was defined as
      three or more consecutive pregnancy losses before 22 weeks of gestation, with a
      previous birth. The control group consisted of all Dutch nullipara delivering a
      singleton (January 2000-2015). Information was obtained from the Dutch Perinatal
      Registry. Outcomes were preeclampsia, preterm birth, post-term birth,
      intrauterine growth restriction, breach position, induction of labor, cesarean
      section, congenital abnormalities, perinatal death and severe hemorrhage in the
      first ongoing pregnancy. Subgroup analyses were performed for women with
      idiopathic SRPL and for women <=35 years. RESULTS: In all, 172 women with SRPL
      and 1 196 178 control women were included. Women with SRPL were older and had a
      higher body mass index; 29.7 years vs. 28.8 years and 25.1 kg/m2 vs. 24.1 kg/m2 ,
      respectively. Women with SRPL more often had a post-term birth (OR 1.86, 95% CI
      1.10-3.17) and more perinatal deaths occurred in women with SRPL compared with
      the control group (OR 5.03, 95% CI 2.48-10.2). Similar results were found in both
      subgroup analyses. CONCLUSIONS: The first ongoing pregnancy of women with
      (idiopathic) SRPL is more often complicated by post-term birth and perinatal
      death. Revealing possible links between SRPL and these pregnancy complications
      might lead to a better understanding of underlying pathophysiology.

PMID- 29055053
TI  - Expression patterns of ion channels and structural proteins in a multimodal cell
      type of the avian optic tectum.
AB  - The midbrain is an important subcortical area involved in distinct functions such
      as multimodal integration, movement initiation, bottom-up, and top-down
      attention. Our group is particularly interested in cellular computation of
      multisensory integration. We focus on the visual part of the avian midbrain, the
      optic tectum (TeO, counterpart to mammalian superior colliculus). This area has a
      layered structure with the great advantage of distinct input and output regions.
      In chicken, the TeO is organized in 15 layers where visual input targets the
      superficial layers while auditory input terminates in deeper layers. One specific
      cell type, the Shepherd's crook neuron (SCN), extends dendrites in both input
      regions. The characteristic feature of these neurons is the axon origin at the
      apical dendrite. The molecular identity of this characteristic region and thus,
      the site of action potential generation are of particular importance to
      understand signal flow and cellular computation in this neuron. We present
      immunohistochemical data of structural proteins (NF200, Ankyrin G, and Myelin)
      and ion channels (Pan-Nav , Nav 1.6, and Kv 3.1b). NF200 is strongly expressed in
      the axon. Ankyrin G is mainly expressed at the axon initial segment (AIS).
      Myelination starts after the AIS as well as the distribution of Nav channels on
      the axon. The subtype Nav 1.6 has a high density in this region. Kv 3.1b is
      restricted to the soma, the primary neurite and the axon branch. The distribution
      of functional molecules in SCNs provides insight into the information flow and
      the integration of sensory modalities in the TeO of the avian midbrain.

PMID- 29055051
TI  - Opposing expression gradients of calcitonin-related polypeptide alpha
      (Calca/Cgrpalpha) and tyrosine hydroxylase (Th) in type II afferent neurons of
      the mouse cochlea.
AB  - Type II spiral ganglion neurons (SGNs) are small caliber, unmyelinated afferents
      that extend dendritic arbors hundreds of microns along the cochlear spiral,
      contacting many outer hair cells (OHCs). Despite these many contacts, type II
      afferents are insensitive to sound and only weakly depolarized by glutamate
      release from OHCs. Recent studies suggest that type II afferents may be cochlear
      nociceptors, and can be excited by ATP released during tissue damage, by analogy
      to somatic pain-sensing C-fibers. The present work compares the expression
      patterns among cochlear type II afferents of two genes found in C-fibers:
      calcitonin-related polypeptide alpha (Calca/Cgrpalpha), specific to pain-sensing
      C-fibers, and tyrosine hydroxylase (Th), specific to low-threshold
      mechanoreceptive C-fibers, which was shown previously to be a selective biomarker
      of type II versus type I cochlear afferents (Vyas et al., ). Whole-mount cochlear
      preparations from 3-week- to 2-month-old CGRPalpha-EGFP (GENSAT) mice showed
      expression of Cgrpalpha in a subset of SGNs with type II-like peripheral
      dendrites extending beneath OHCs. Double labeling with other molecular markers
      confirmed that the labeled SGNs were neither type I SGNs nor olivocochlear
      efferents. Cgrpalpha starts to express in type II SGNs before hearing onset, but
      the expression level declines in the adult. The expression patterns of Cgrpalpha
      and Th formed opposing gradients, with Th being preferentially expressed in
      apical and Cgrpalpha in basal type II afferent neurons, indicating heterogeneity
      among type II afferent neurons. The expression of Th and Cgrpalpha was not
      mutually exclusive and co-expression could be observed, most abundantly in the
      middle cochlear turn.

PMID- 29055055
TI  - E-Cadherin Gene Polymorphisms and Susceptibility to Urolithiasis in Iraqi
      Children.
AB  - AIM: This case/control study aimed to assess the impact of two SNPs in the
      promoter region of CDH1 gene (-160C>A and -347G>GA) on urinary stone formation in
      a sample of Iraqi children. METHODS: Forty-seven children with urolithiasisand 50
      age- and gender-matched healthy controls. DNA was isolated from peripheral blood
      and direct sequencing was used for genotyping. RESULTS: The homozygous genotype
      of the SNP CHD1 -160C>A was more frequent in control than cases (18% vs 6.38%)
      with significant difference (OR= 0.229, 95%CI= 0.056-0.943, P=0.041).
      Furthermore, cases showed significantly less frequency of the mutant allele
      (allele A) of this SNP (OR= 0.403, 95%C=0.210-0.776, P=0.007). CONCLUSION: These
      results strongly indicate a protective role of allele A of the SNP CHD1 -160C>A
      against urinary calculi formation in children.

PMID- 29055054
TI  - Multicenter prospective evaluation study of endoscopic ultrasound-guided
      hepaticogastrostomy combined with antegrade stenting (with video).
AB  - BACKGROUND AND AIM: Endoscopic ultrasonography-guided hepaticogastrostomy (EUS
      HGS) is often indicated for advanced stage patients. Therefore it is important to
      prevent adverse events associated with EUS-HGS procedures and obtain long stent
      patency. EUS-guided antegrade stenting (AS) has been developed as an advanced
      technique. Thus, to prevent adverse events and achieve long stent patency, EUS-AS
      combined with EUS-HGS (EUS-HGAS) has been reported. The aim of the present study
      was to evaluate the technical feasibility and efficacy of EUS-HGAS in a
      multicenter, prospective study. METHODS: This prospective study was carried out
      at each hospital of the Therapeutic Endoscopic Ultrasound Group. Primary endpoint
      of this multicenter prospective study was stent patency of EUS-HGAS. RESULTS: A
      total of 49 patients were enrolled. Technical success rate of EUS-HGS was 95.9%
      (47/49). EUS-AS failed in five patients because the guidewire could not be
      advanced into the intestine across the bile duct obstruction site. Therefore, EUS
      HGAS was successfully carried out in 40 patients (technical success rate: 85.7%).
      Median overall survival was 114 days. Median stent patency including stent
      dysfunction and patient death was 114 days. In contrast, mean stent patency was
      320 days. Adverse events were seen in 10.2% (5/49) of cases. Hyperamylasemia was
      seen in four patients, and bleeding was seen in one patient. CONCLUSIONS: The
      present study is the first to evaluate EUS-HGAS. EUS-HGAS has clinical benefit
      for obtaining long stent patency and avoiding adverse events, although the
      possibility of acute pancreatitis as a result of obstruction of the orifice of
      the pancreatic duct must be considered.

PMID- 29055057
TI  - Sperm competition, but not major histocompatibility divergence, drives
      differential fertilization success between alternative reproductive tactics in
      Chinook salmon.
AB  - Post-copulatory sexual selection processes, including sperm competition and
      cryptic female choice (CFC), can operate based on major histocompatibility (MH)
      genes. We investigated sperm competition between male alternative reproductive
      tactics [jack (sneaker) and hooknose (guard)] of Chinook salmon (Oncorhynchus
      tshawytscha). Using a full factorial design, we examined in vitro competitive
      fertilization success of paired jack and hooknose males at three time points
      after sperm activation (0, 15 and 60 s) to test for male competition, CFC and
      time effects on male fertilization success. We also examined egg-mediated CFC at
      two MH genes by examining both the relationship between competitive fertilization
      success and MH divergence as well as inheritance patterns of MH alleles in
      resulting offspring. We found that jacks sired more offspring than hooknose males
      at 0 s post-activation; however, jack fertilization success declined over time
      post-activation, suggesting a trade-off between sperm speed and longevity.
      Enhanced fertilization success of jacks (presumably via higher sperm quality) may
      serve to increase sneaker tactic competitiveness relative to dominant hooknose
      males. We also found evidence of egg-mediated CFC (i.e. female * male
      interaction) influencing competitive fertilization success; however, CFC was not
      acting on the MH genes as we found no relationship between fertilization success
      and MH II beta1 or MH I alpha1 divergence and we found no deviations from
      Mendelian inheritance of MH alleles in the offspring. Our study provides insight
      into evolutionary mechanisms influencing variation in male mating success within
      alternative reproductive tactics, thus underscoring different strategies that
      males can adopt to attain success.

PMID- 29055058
TI  - The neural oscillations of speech processing and language comprehension: state of
      the art and emerging mechanisms.
AB  - Neural oscillations subserve a broad range of functions in speech processing and
      language comprehension. On the one hand, speech contains-somewhat-repetitive
      trains of air pressure bursts that occur at three dominant amplitude modulation
      frequencies, physically marking the linguistically meaningful progressions of
      phonemes, syllables and intonational phrase boundaries. To these acoustic events,
      neural oscillations of isomorphous operating frequencies are thought to
      synchronise, presumably resulting in an implicit temporal alignment of periods of
      neural excitability to linguistically meaningful spectral information on the
      three low-level linguistic description levels. On the other hand, speech is a
      carrier signal that codes for high-level linguistic meaning, such as syntactic
      structure and semantic information-which cannot be read from stimulus acoustics,
      but must be acquired during language acquisition and decoded for language
      comprehension. Neural oscillations subserve the processing of both syntactic
      structure and semantic information. Here, I synthesise a mapping from each
      linguistic processing domain to a unique set of subserving oscillatory mechanisms
      the mapping is plausible given the role ascribed to different oscillatory
      mechanisms in different subfunctions of cortical information processing and
      faithful to the underlying electrophysiology. In sum, the present article
      provides an accessible and extensive review of the functional mechanisms that
      neural oscillations subserve in speech processing and language comprehension.

PMID- 29055056
TI  - Everolimus in advanced, progressive, well-differentiated, non-functional
      neuroendocrine tumors: RADIANT-4 lung subgroup analysis.
AB  - In the phase III RADIANT-4 study, everolimus improved median progression-free
      survival (PFS) by 7.1 months in patients with advanced, progressive, well
      differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal
      neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence
      interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the
      outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were
      randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive
      care. This is a post hoc analysis of the lung subgroup with PFS, by central
      radiology review, as the primary endpoint; secondary endpoints included objective
      response rate and safety measures. Ninety of the 302 patients enrolled in the
      study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95%
      CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9
      5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More
      patients who received everolimus (58%) experienced tumor shrinkage compared with
      placebo (13%). Most frequently reported (>=5% incidence) grade 3-4 drug-related
      adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%),
      hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with
      advanced, progressive, well-differentiated, non-functional lung NET, treatment
      with everolimus was associated with a median PFS improvement of 5.6 months, with
      a safety profile similar to that of the overall RADIANT-4 cohort. These results
      support the use of everolimus in patients with advanced, non-functional lung NET.
      The trial is registered with ClinicalTrials.gov (no. NCT01524783).

PMID- 29055059
TI  - Application of the broadband collision-induced dissociation (bbCID) mass
      spectrometry approach for protein glycosylation and phosphorylation analysis.
AB  - RATIONALE: Analysis of post-translationally modified peptides by mass
      spectrometry (MS) remains incomplete, in part due to incomplete sampling of all
      peptides which is inherent to traditional data-dependent acquisition (DDA). An
      alternative MS approach, data-independent acquisition (DIA), enables
      comprehensive recording of all detectable precursor and product ions, independent
      of precursor intensity. The use of broadband collision-induced dissociation
      (bbCID), a DIA method, was evaluated for the identification of protein
      glycosylation and phosphorylation. METHODS: bbCID was applied to identify
      glycopeptides and phosphopeptides generated from standard proteins using a high
      resolution Bruker maXis 3G mass spectrometer. In bbCID, precursor and product ion
      spectra were obtained by alternating low and high collision energy. Precursor
      ions were assigned manually based on the detection of diagnostic ions specific to
      either glycosylation or phosphorylation. The composition of the glycan
      modification was resolved in the positive ion mode, while the level of
      phosphorylation was investigated in the negative ion mode. RESULTS: The results
      demonstrate for the first time that the use of a bbCID approach is suitable for
      the identification of glycopeptides and phosphopeptides based on the detection of
      specific diagnostic and associated precursor ions. The novel use of bbCID in
      negative ion mode allowed the discrimination of singly and multiply
      phosphorylated peptides based on the detection of phosphate diagnostic ions. The
      results also demonstrate the ability of this approach to allow the identification
      of glycan composition in N- and O-linked glycopeptides, in positive ion mode.
      CONCLUSIONS: We contend that bbCID is a valuable addition to the existing toolkit
      for PTM discovery. Moreover, this technique could be employed to direct targeted
      proteomics methods, particularly where there is no a priori information on
      glycosylation or phosphorylation status. This technique is immediately relevant
      to the characterisation of individual proteins or biological samples of low
      complexity, as demonstrated for the analysis of the glycosylation status of a
      therapeutic protein.

PMID- 29055060
TI  - Gonadotropin-releasing hormone agonists for ovarian protection during cancer
      chemotherapy: systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness of gonadotropin-releasing hormone
      agonist (GnRHa) administration before and/or during cancer chemotherapy for the
      protection of ovarian reserve in premenopausal women without prior diagnosis of
      infertility. METHODS: This was a systematic review and meta-analysis of
      randomized controlled trials (RCTs) comparing administration of GnRHa before
      and/or during chemotherapy vs chemotherapy alone. Eligible participants were
      premenopausal women at any stage of cancer, without previous diagnosis of
      infertility. An electronic database search in MEDLINE, CENTRAL, LILACS and
      ClinicalTrials.gov was performed. After selecting eligible studies, the relative
      risk (RR) was assessed for primary ovarian insufficiency (POI)/amenorrhea and for
      spontaneous pregnancy after completion of treatment. RESULTS: Thirteen RCTs
      comparing concurrent use of GnRHa and chemotherapy (609 participants) with
      chemotherapy alone (599 participants) were eligible for meta-analysis. All trials
      were open-label and patients had been treated for breast cancer (n = 1099) or
      lymphoma (n = 109). GnRHa had a significant benefit on the risk of POI/amenorrhea
      (RR, 0.60; 95% CI, 0.45-0.79), which persisted in subgroup analysis for breast
      cancer (RR, 0.57; 95% CI, 0.43-0.77) but not for lymphoma patients (RR, 0.70; 95%
      CI, 0.20-2.47). The rate of spontaneous pregnancy after completion of treatment
      was higher in women receiving GnRHa plus chemotherapy compared with those
      receiving chemotherapy alone (RR, 1.43; 95% CI, 1.01-2.02). Overall, the quality
      of evidence was low due to the unclear risk of bias, short follow-up and lack of
      objective assessment of ovarian function and reserve. CONCLUSIONS: Evidence,
      albeit of low quality, supports the use of GnRHa before and/or during
      chemotherapy to reduce the risk of POI and increase the probability of
      spontaneous pregnancy in the short term. Further high quality RCTs with more
      accurate assessment of ovarian reserve are needed to support definitive
      recommendations for clinical practice. Copyright (c) 2017 ISUOG. Published by
      John Wiley & Sons Ltd.

PMID- 29055061
TI  - Preservation of stem cells in androgenetic alopecia.

PMID- 29055062
TI  - Cognition, quality-of-life, and symptom clusters in breast cancer: Using Bayesian
      networks to elucidate complex relationships.
AB  - OBJECTIVE: Breast cancer patients frequently complain of cognitive dysfunction
      during chemotherapy. Patients also report experiencing a cluster of sleep
      problems, fatigue, and depressive symptoms during chemotherapy. We aimed to
      understand the complex dynamic interrelationships of depression, fatigue, and
      sleep to ultimately elucidate their role in cognitive performance and quality of
      life amongst breast cancer survivors undergoing chemotherapy treatment. METHODS:
      Our study sample comprised 74 newly diagnosed stage I to III breast cancer
      patients scheduled to receive chemotherapy. An objective neuropsychological test
      battery and self-reported fatigue, mood, sleep quality, and quality of life were
      collected at 3 time points: before the start of chemotherapy (baseline: BL), at
      the end of cycle 4 chemotherapy (C4), and 1 year after the start of chemotherapy
      (Y1). We applied novel Bayesian network methods to investigate the role of
      sleep/fatigue/mood on cognition and quality of life prior to, during, and after
      chemotherapy. RESULTS: The fitted network exhibited strong direct and indirect
      links between symptoms, cognitive performance, and quality of life. The only
      symptom directly linked to cognitive performance was C4 sleep quality; at C4,
      fatigue was directly linked to sleep and thus indirectly influenced cognitive
      performance. Mood strongly influenced concurrent quality of life at C4 and Y1.
      Regression estimates indicated that worse sleep quality, fatigue, and mood were
      negatively associated with cognitive performance or quality of life. CONCLUSIONS:
      The Bayesian network identified local structure (eg, fatigue-mood-QoL or sleep
      cognition) and possible intervention targets (eg, a sleep intervention to reduce
      cognitive complaints during chemotherapy).

PMID- 29055063
TI  - Added value of chromosomal microarray analysis over karyotyping in early
      pregnancy loss: systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate the increased test success rate and incremental yield of
      chromosomal microarray analysis (CMA) over conventional karyotyping in detection
      of pathogenic copy number variants (CNVs) and variants of unknown significance
      (VOUS) in early pregnancy loss. METHOD: This was a systematic review conducted in
      accordance with PRISMA criteria. All articles identified in PubMed, Ovid MEDLINE
      and Web of Science, between January 2000 and April 2017, that described CNVs in
      early pregnancy losses (up to 20 weeks) were included. Risk differences were
      pooled to estimate the incremental yield of CMA over karyotyping overall, and
      after stratification. In addition, test success rate, defined as the proportion
      of informative results, was compared in series in which CMA and karyotyping were
      performed concurrently. RESULTS: Twenty-three studies, reporting on 5507
      pregnancy losses up to 20 weeks with full data available, met the inclusion
      criteria for analysis. In the series in which CMA and karyotyping were performed
      concurrently, CMA showed a significant improvement in success rate, providing
      informative results in 95% (95% CI, 94-96%) of cases compared with karyotyping in
      which informative results were provided in 68% (95% CI, 66-70%) of cases.
      Combined data from reviewed studies revealed that incremental yields of CMA over
      karyotyping were 2% (95% CI, 1-2%) for pathogenic CNVs and 4% (95% CI, 3-6%) for
      VOUS. The most common pathogenic CNVs reported were 22q11.21 and 1p36.33
      deletion. CONCLUSION: In comparison with conventional karyotyping, CMA provides a
      significant increase in test success rate and incremental diagnostic yield in
      early pregnancy loss. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons
      Ltd.

PMID- 29055064
TI  - Clinical relevance of peroxisome proliferator-activated receptor-gamma gene
      polymorphisms with sepsis.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a
      regulator of inflammation. This study aimed to explore associations between
      PPARgamma gene single-nucleotide polymorphisms (SNPs) and susceptibility to and
      clinical outcome of sepsis in the North China Han population. METHODS: This study
      included 303 patients with sepsis and 303 controls. We conducted genetic typing
      for 13 common PPARgamma gene SNPs (improved multiplex ligation detection
      reaction), linkage disequilibrium mapping, and haplotype inference. Associations
      between SNP genotypes/haplotypes and sepsis susceptibility and outcome (septic
      shock, organ dysfunction, or death) were assessed using unconditional logistic
      regression analysis. RESULTS: For rs2972164, patients with genotypes CT/CT+TT had
      higher risk of sepsis than genotype CC (odds ratio [95% CI]: 1.74 [1.05-2.86], P
      = .03 and 1.72 [1.06-2.80], P = .026, respectively); the T allele was associated
      with increased sepsis risk compared with the C allele (1.64 [1.04-2.58], P =
      .033). For rs1801282, genotypes CG/CG+GG had lower risk of sepsis than genotype
      CC (0.55 [0.33-0.92], P = .024 and 0.57 [0.35-0.95], P = .03, respectively); the
      G allele was associated with decreased sepsis risk compared with the C allele
      (0.62 [0.39-1.01], P = .055). For rs4135275, genotypes AG/AG+GG had higher risk
      of severe organ dysfunction (multiple organ dysfunction syndrome score >8) than
      genotype AA (2.66 [1.16-6.09], P = .038 and 2.21 [1.00-4.85], P = .042,
      respectively). Haplotype TAT (rs2972164, rs4684846, and rs17036188) was
      associated with increased sepsis risk (1.66 [1.03-2.67], P = .038). CONCLUSIONS:
      No mutation was correlated with septic shock or death. PPARgamma gene
      polymorphisms may play a role in the occurrence and progression of sepsis in the
      North China Han population.

PMID- 29055065
TI  - Simultaneous determination of usnic, diffractaic, evernic and barbatic acids in
      rat plasma by ultra-high-performance liquid chromatography-quadrupole exactive
      Orbitrap mass spectrometry and its application to pharmacokinetic studies.
AB  - Usnea longissima Ach. (Usnea) is used in pharmaceuticals, food and cosmetics.
      Evernic acid (EA), barbatic acid (BA), diffractaic acid (DA) and usnic acid (UA)
      are the most typical ingredients in U. longissima and exert a wide variety of
      biological functions. The study aimed to develop a sensitive method for
      simultaneous analysis of EA, BA, DA and UA in rat plasma and was applied to
      pharmacokinetic studies after consumption of UA and ethanol extract from U.
      longissima (UE). The samples were separated on a BEH C18 column by gradient
      elution with 0.5% formic acid in water and in methanol. The relative molecular
      masses of analytes were obtained in full-scan range from 50.0 to 750.0 m/z under
      negative ionization mode by UPLC-Q-Exactive Orbitrap MS. All validation
      parameters, such as lower limit of quantitation, linearity, specificity,
      precision, accuracy, extraction recovery, matrix effect and stability, were
      within acceptable ranges and the method was appropriate for biological specimen
      analysis. The pharmacokinetic results indicated that the absolute
      bioavailabilities of UA after oral administration of UA and UE reached 69.2 and
      146.9%, respectively. Compared with UA in UE, the relative bioavailability of DA,
      BA and EA reached 103.7, 10.4 and 0.7% after oral administration of UE.

PMID- 29055066
TI  - Longitudinal study showed that the quality of life of Finnish adolescents with
      cerebral palsy continued to be relatively good.
AB  - AIM: This longitudinal study examined what perceptions paediatric patients with
      cerebral palsy (CP) and their caregivers had of the patient's quality of life
      (QoL). It examined changing trends as children with CP became adolescents and
      examined the feasibility of the Finnish version of the CP QOL-Teen questionnaire.
      METHODS: Carried out in autumn 2015, this study formed part of the multi-centre
      Finnish national CP project and aimed to validate the CP QOL-Teen questionnaire,
      which was posted to 54 adolescents and their caregivers. They included 24 who had
      responded to CP QOL-Child questionnaire in 2013. RESULTS: The questionnaires were
      returned by 27 pairs of adolescents and caregivers and one extra caregiver also
      responded. Of these, 24 pairs had taken part in the 2013 survey. The internal
      consistencies of the sum variables were found to be acceptable in all cases.
      Overall QoL showed an average score of 81.8 on a scale from 0 to 100. Adolescents
      reported significantly higher QoL than their caregivers. There were no
      significant differences between the responses of the children and adolescents.
      CONCLUSION: We showed that QoL was relatively good in childhood and adolescence.
      The Finnish version of the CP QOL-Teen questionnaire was an appropriate clinical
      tool for assessing QoL.

PMID- 29055067
TI  - Cutaneous atypical papular CD8+ lymphoproliferative disorder at acral sites in a
      renal transplant patient.
AB  - A 20-year-old woman presented with a 2-month history of an acute symmetrical
      eruption, manifesting as asymptomatic ill-defined erythematous macules and
      hyperkeratotic papules on the palms. The patient was a renal transplant
      recipient, and the lesions had developed 2 months post-transplantation.
      Histologically, the eruption shared features of a reactive inflammatory condition
      called papular eruption of atypical CD8+ lymphocytes as well as primary cutaneous
      acral CD8+ T-cell lymphoma (a provisional indolent entity in the new World Health
      Organisation classification of lymphoid neoplasms, 2016). The latter disorder has
      been described to occur at acral sites in immunocompetent patients, whereas the
      former has previously been described only in patients infected with human
      immunodeficiency virus. The lesions in our patient healed after topical treatment
      with corticosteroids and alteration of immunosuppressive therapy, supporting the
      role of immunosuppression in this case. We classified our patient's condition as
      lying in the spectrum of the aforementioned two conditions, but the relationship
      between both diseases remains to be clarified. Awareness of these unusual
      conditions may prevent the use of unnecessary aggressive therapies in similar
      patients.

PMID- 29055068
TI  - Traumatic subungual neuroma.

PMID- 29055069
TI  - Evidence of evolutionary optimization of fatty acid length and unsaturation.
AB  - The lipid composition of cell membranes exerts a crucial influence on cell
      physiology. Indeed, one double bond triggers membrane fluidity, essential for
      cell functionality, but additional double bonds increase the susceptibility to
      peroxidation, which produces reactive compounds that impair the viability of
      cells. It has therefore been suggested, but never tested in an extensive
      comparative context, that the composition of membrane fatty acids has been
      optimized during evolution. A similar prediction has been made for fatty acid
      chain length, on which susceptibility to peroxidation also depends. Here I tested
      for stabilizing selection on fatty acid composition by evaluating the fitting of
      the single stationary peak (SSP) model of evolution to a large data set from 107
      species of birds, against alternative evolutionary models. I found that across
      species variation in average chain length and in the proportion of
      monounsaturated fatty acids (MUFAs), but not in the proportion of polyunsaturated
      (PUFAs) nor saturated (SFAs) fatty acids, was better explained by SSP models than
      by other models. Results show optimum values of fatty acid chain length and
      proportion of MUFAs of 18 C atoms and 25.5% mol, respectively, the strength of
      stabilizing selection being particularly high in chain length. This is the first
      evidence of evolutionary optimization in fatty acid composition, suggesting that
      certain values may have been selected because of their adaptive capacity to
      minimize susceptibility to lipid peroxidation.

PMID- 29055070
TI  - Climate change leads to increasing population density and impacts of a key island
      invader.
AB  - The considerable threats of invasive rodents to island biodiversity are likely to
      be compounded by climate change. Forecasts for such interactions have been most
      pronounced for the Southern Ocean islands where ameliorating conditions are
      expected to decrease thermal and resource restrictions on rodents. Firm evidence
      for changing rodent populations in response to climate change, and demonstrations
      of associated impacts on the terrestrial environment, are nonetheless entirely
      absent for the region. Using data collected over three decades on sub-Antarctic
      Marion Island, we tested empirically whether mouse populations have changed
      through time and whether these changes can be associated significantly with
      changing abiotic conditions. Changes in invertebrate populations, which have
      previously been attributed to mouse predation, but with little explicit
      demographic analysis, were also examined to determine whether they can be
      associated with changing mouse populations. The total number of mice on the
      island at annual peak density increased by 430.0% between 1979-1980 and 2008
      2011. This increase was due to an advanced breeding season, which was robustly
      related to the number of precipitation-free days during the non-breeding season.
      Mice directly reduced invertebrate densities, with biomass losses of up to two
      orders of magnitude in some habitats. Such invertebrate declines are expected to
      have significant consequences for ecosystem processes over the long term. Our
      results demonstrate that as climate change continues to create ameliorating
      conditions for invasive rodents on sub-Antarctic islands, the severity of their
      impacts will increase. They also emphasize the importance of rodent eradication
      for the restoration of invaded islands.

PMID- 29055071
TI  - Advanced diagnostic endoscopy in the lower gastrointestinal tract: A review of
      JGES core sessions.
AB  - At each of the 89th to the 92nd congresses of the Japan Gastroenterological
      Endoscopy Society, a series of featured discussion sessions concerning advanced
      diagnostic endoscopy in the lower gastrointestinal tract were presented. In
      total, 45 lectures were presented in this subject area. It was shown that, in
      recent years, several convenient and less invasive colonoscopic modalities have
      been developed. This review article summarizes these core sessions and the
      efficacy of the techniques discussed.

PMID- 29055072
TI  - Outcome of assisted reproduction in women with congenital uterine anomalies: a
      prospective observational study.
AB  - OBJECTIVES: To assess the prevalence of congenital uterine anomalies, including
      arcuate uterus, and their effect on reproductive outcome in subfertile women
      undergoing assisted reproduction. METHODS: Consecutive women referred for
      subfertility between May 2009 and November 2015 who underwent assisted
      reproduction were included in the study. As part of the initial assessment, each
      woman underwent three-dimensional transvaginal sonography. Uterine morphology was
      classified using the modified American Fertility Society (AFS) classification of
      congenital uterine anomalies proposed by Salim et al. If the external contour of
      the uterus was uniformly convex or had an indentation of < 10 mm, but there was a
      cavity indentation, it was defined as arcuate or septate. Arcuate uterus was
      further defined as the presence of a concave fundal indentation with a central
      point of indentation at an obtuse angle. Subseptate uterus was defined as the
      presence of a septum, not extending to the cervix, with the central point of the
      septum at an acute angle; if the septum extended to the internal cervical os, the
      uterus was defined as septate. Reproductive outcomes, including live birth,
      clinical pregnancy and preterm birth, were compared between women with a normal
      uterus and those with a congenital uterine anomaly. Subgroup analysis by type of
      uterine morphology and logistic regression analysis adjusted for age, body mass
      index, levels of anti-Mullerian hormone, antral follicle count and number and day
      of embryo transfer were performed. RESULTS: A total of 2375 women were included
      in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a
      congenital uterine anomaly. The most common anomalies were arcuate (n = 387
      (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was
      similar between women with a uterine anomaly and those with a normal uterus (35%
      vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of
      the newborn were also similar between the two groups. Preterm birth before 37
      weeks' gestation was more common in women with uterine anomalies than in controls
      (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed
      no difference in the incidence of live birth and clinical pregnancy for women
      with an arcuate uterus, but indicated worse pregnancy outcome in women with other
      major anomalies (P = 0.042 and 0.048, respectively). CONCLUSIONS: Congenital
      uterine anomalies as a whole, when defined using the modified AFS classification,
      do not affect clinical pregnancy or live-birth rates in women following assisted
      reproduction, but do increase the incidence of preterm birth. The presence of
      uterine abnormalities more severe than arcuate uterus significantly worsens all
      pregnancy outcomes. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29055074
TI  - Can we make physiological research better?

PMID- 29055073
TI  - PpNAC1, a main regulator of phenylalanine biosynthesis and utilization in
      maritime pine.
AB  - The transcriptional regulation of phenylalanine metabolism is particularly
      important in conifers, long-lived species that use large amounts of carbon in
      wood. Here, we show that the Pinus pinaster transcription factor, PpNAC1, is a
      main regulator of phenylalanine biosynthesis and utilization. A phylogenetic
      analysis classified PpNAC1 in the NST proteins group and was selected for
      functional characterization. PpNAC1 is predominantly expressed in the secondary
      xylem and compression wood of adult trees. Silencing of PpNAC1 in P. pinaster
      results in the alteration of stem vascular radial patterning and the down
      regulation of several genes associated with cell wall biogenesis and secondary
      metabolism. Furthermore, transactivation and EMSA analyses showed that PpNAC1 is
      able to activate its own expression and PpMyb4 promoter, while PpMyb4 is able to
      activate PpMyb8, a transcriptional regulator of phenylalanine and lignin
      biosynthesis in maritime pine. Together, these results suggest that PpNAC1 is a
      functional ortholog of the ArabidopsisSND1 and NST1 genes and support the idea
      that key regulators governing secondary cell wall formation could be conserved
      between gymnosperms and angiosperms. Understanding the molecular switches
      controlling wood formation is of paramount importance for fundamental tree
      biology and paves the way for applications in conifer biotechnology.

PMID- 29055075
TI  - Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with
      Hip Osteoarthritis.
AB  - BACKGROUND: Factors such as age, gender, and genetic polymorphisms may explain
      individual differences in pain phenotype. Genetic associations with pain
      sensitivity have previously been investigated in osteoarthritis patients, with a
      focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role
      as well. Osteoarthritis is a common joint disease, and many patients suffering
      from this disease are thought to have increased sensitivity to noxious stimuli
      resulting from sensitization in the nociceptive system. The aim of this study was
      to investigate if genetic variants of mu, kappa, and delta opioid receptor genes
      (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT)
      influenced the pain phenotype in patients with osteoarthritis. METHODS: The
      frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed
      preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned
      pain modulation effect, and (4) pressure stimulation at the tibia in both the
      affected and the unaffected leg. RESULTS: Ninety-two patients (mean age 66 years)
      with unilateral hip osteoarthritis were included in the study. Carriage of the
      OPRM1 rs589046T allele was found to be associated with increased pain ratings
      during hip rotation (P = 0.04) and increased conditioned pain modulation (P =
      0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with
      an increased pain detection threshold to contact heat stimulation (P = 0.001). No
      other associations were found (all P > 0.05). CONCLUSION: Results from the
      present study suggest that, in patients with hip osteoarthritis, genetic variants
      in OPRM1 and OPRD1 may contribute to the pain phenotype.

PMID- 29055076
TI  - Molecular dissection of protein-protein interactions between integrin alpha5beta1
      and the Helicobacter pylori Cag type IV secretion system.
AB  - The more severe strains of the bacterial human pathogen Helicobacter pylori
      produce a type IV secretion system (cagT4SS) to inject the oncoprotein cytotoxin
      associated gene A (CagA) into gastric cells. This syringe-like molecular
      apparatus is prolonged by an external pilus that exploits integrins as receptors
      to mediate the injection of CagA. The molecular determinants of the interaction
      of the cagT4SS pilus with the integrin ectodomain are still poorly understood. In
      this study, we have used surface plasmon resonance (SPR) to generate a
      comprehensive analysis of the protein-protein interactions between purified CagA,
      CagL, CagI, CagY repeat domain II (CagYRRII ), CagY C-terminal domain (CagYB10 )
      and integrin alpha5beta1 ectodomain (alpha5beta1E ) or headpiece domain
      (alpha5beta1HP ). We found that CagI, CagA, CagL and CagYB10 but not CagYRRII
      were able to interact with alpha5beta1E with affinities similar to the one
      observed for alpha5beta1E interaction with its physiological ligand fibronectin.
      We further showed that integrin activation and its associated conformational
      change increased CagA, CagL and CagYB10 affinities for the receptor. Furthermore,
      CagI did not interact with integrin unless the receptor was in open conformation.
      CagI, CagA but not CagL and CagYB10 interacted with the alpha5beta1HP . Our SPR
      study also revealed novel interactions between CagA and CagL, CagA and CagYB10 ,
      and CagA and CagI. Altogether, our data map the network of interactions between
      host-cell alpha5beta1 integrin and the cagT4SS proteins and suggest that
      activation of the receptor promotes interactions with the secretion apparatus and
      possibly CagA injection.

PMID- 29055077
TI  - Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with
      Tunisian inflammatory bowel disease.
AB  - OBJECTIVE: The common association between NOD2/CARD15 and TLR4 gene variants with
      inflammatory bowel disease (IBD) has not been replicated in all studies. We
      studied the polymorphism of these two genes in Tunisian patients with IBD.
      METHODS: Polymorphisms of NOD2 (R702W, G908R and L1007fs) and TLR4 (Asp299Gly and
      Thr399Ile) genes were analyzed in 106 patients with IBD (68 with ulcerative
      colitis [UC], 38 with Crohn's disease [CD]) and 160 healthy controls using
      polymerase chain reaction-restriction fragment length polymorphism. Genotypes and
      phenotypes were correlated. RESULTS: The mutated allele of TLR4-Thr399Ile was
      strongly associated with IBD (9.4% in IBD, 7.4% in UC and 13.2% in CD vs 2.5% in
      controls; P = 0.0004, 0.014 and 0.00006, respectively). Heterozygous genotypes
      were significantly more frequent in patients with IBD (17.0%), UC (14.7%) and CD
      (21.1%) than in controls (5.0%) (P = 0.0012, 0.012 and 0.001, respectively).
      Interestingly, the wild genotype was found to be protective (odds ratio 0.24).
      The mutated allele of TLR4-Asp299Gly was more frequent in controls (6.8%) than in
      patients with IBD (2.9%). A phenotypic correlation of Asp299Gly-AG genotype with
      arthritis in UC patients was detected (P = 0.003). Regarding the NOD2 gene, the
      common variations studied were not polymorphic and there was no genetic
      association with IBD. CONCLUSION: The TLR4-Thr399Ile variant was strongly
      associated with susceptibility to IBD, whereas TLR4-Asp299Gly seems to play a
      role in the clinical expression of UC. The rarity and non-association of NOD2
      mutations with IBD may reveal a genetic characteristic of the population in our
      region.

PMID- 29055079
TI  - Health sciences libraries in the United States: new directions.
AB  - This article is the third in a series in this regular feature. The intention of
      the series is to look at important global developments in health science
      libraries. These articles will serve as a road map, describing the key changes in
      the field and exploring factors driving these changes. The present article by the
      current president of the Medical Library Association outlines two important
      developments in the United States. The topics chosen for consideration are
      national initiatives in the United States impacting health sciences libraries and
      librarians and enhanced roles for U.S. health sciences librarians in providing
      support for research. J.M.

PMID- 29055078
TI  - Neoadjuvant chemoradiation for non-metastatic pancreatic cancer increases margin
      negative and node-negative rates at resection.
AB  - OBJECTIVE: To compare neoadjuvant to adjuvant chemoradiation in non-metastatic
      pancreatic cancer patients. METHODS: Single-institution data were obtained for
      patients with non-metastatic pancreatic cancer treated with concurrent
      chemoradiation from 2011 to 2014. Univariate analyses were performed to evaluate
      clinical and pathological outcomes. RESULTS: Fifty-two well-matched patients were
      enrolled (21 underwent neoadjuvant chemoradiation, 11 with adjuvant
      chemoradiation and 20 in the definitive group). Median tumor size was 2.6 cm
      pretreatment and 2.5 cm after neoadjuvant chemoradiation but 3.2 cm on pathology,
      with a treatment effect in 95.2% of specimens. Clinical node positivity at
      diagnosis for neoadjuvant and adjuvant chemoradiation groups was similar (28.6%
      vs 27.3%, P = 0.12). Of the 36 neoadjuvant patients, 21 (58.3%) underwent
      complete resection. In the neoadjuvant vs adjuvant chemoradiation groups,
      positive margins were decreased (4.8% vs 63.6%, P < 0.001), as was pathological
      nodal positivity (23.8% vs 90.9%, P < 0.001). After a median follow-up of 13.3
      months, locoregional control for neoadjuvant and adjuvant chemoradiation was 7.7
      and 7.2 months, respectively (P = 0.12) and the definitive group was 1.2 months
      (P = 0.014 compared with the surgical cohort). One-year overall survival was
      better with neoadjuvant than with adjuvant chemoradiation but this was not
      significant (94% vs 82%, P = 0.20); 1-year survival for the definitive group was
      59% (P = 0.03 compared with the surgical cohort). CONCLUSIONS: Neoadjuvant
      chemoradiation remains a promising approach for non-metastatic pancreatic cancer
      for improving resectability and pathological and clinical findings. Computed
      tomography may not fully demonstrate the effectiveness of neoadjuvant treatment.

PMID- 29055080
TI  - Matrix approach to land carbon cycle modeling: A case study with the Community
      Land Model.
AB  - The terrestrial carbon (C) cycle has been commonly represented by a series of C
      balance equations to track C influxes into and effluxes out of individual pools
      in earth system models (ESMs). This representation matches our understanding of C
      cycle processes well but makes it difficult to track model behaviors. It is also
      computationally expensive, limiting the ability to conduct comprehensive
      parametric sensitivity analyses. To overcome these challenges, we have developed
      a matrix approach, which reorganizes the C balance equations in the original ESM
      into one matrix equation without changing any modeled C cycle processes and
      mechanisms. We applied the matrix approach to the Community Land Model (CLM4.5)
      with vertically-resolved biogeochemistry. The matrix equation exactly reproduces
      litter and soil organic carbon (SOC) dynamics of the standard CLM4.5 across
      different spatial-temporal scales. The matrix approach enables effective
      diagnosis of system properties such as C residence time and attribution of global
      change impacts to relevant processes. We illustrated, for example, the impacts of
      CO2 fertilization on litter and SOC dynamics can be easily decomposed into the
      relative contributions from C input, allocation of external C into different C
      pools, nitrogen regulation, altered soil environmental conditions, and vertical
      mixing along the soil profile. In addition, the matrix tool can accelerate model
      spin-up, permit thorough parametric sensitivity tests, enable pool-based data
      assimilation, and facilitate tracking and benchmarking of model behaviors.
      Overall, the matrix approach can make a broad range of future modeling activities
      more efficient and effective.

PMID- 29055081
TI  - A new endoscopic technique to close big nasal septal perforations: Prospective
      evaluation of the double meat hook technique in 19 consecutive cases.

PMID- 29055082
TI  - Supramolecular aggregation of aquaporin-4 is different in muscle and brain:
      correlation with tissue susceptibility in neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central
      nervous system (CNS) caused by autoantibodies (NMO-IgG) against the water channel
      aquaporin-4 (AQP4). Though AQP4 is also expressed outside the CNS, for example in
      skeletal muscle, patients with NMO generally do not show clinical/diagnostic
      evidence of skeletal muscle damage. Here, we have evaluated whether AQP4
      supramolecular organization is at the basis of the different tissue
      susceptibility. Using immunofluorescence we found that while the sera of our
      cohort of patients with NMO gave typical perivascular staining in the CNS, they
      were largely negative in the skeletal muscle. This conclusion was obtained using
      human, rat and mouse skeletal muscle including the AQP4-KO mouse. A biochemical
      analysis using a new size exclusion chromatography approach for AQP4
      suprastructure fractionation revealed substantial differences in supramolecular
      AQP4 assemblies and isoform abundance between brain and skeletal muscle matching
      a lower binding affinity of NMO-IgG to muscle compared to the brain. Super
      resolution microscopy analysis with g-STED revealed different AQP4 organization
      in native tissues, while in the brain perivascular astrocyte endfoot membrane
      AQP4 was mainly organized in large interconnected and raft-like clusters, in the
      sarcolemma of fast-twitch fibres AQP4 aggregates often appeared as small,
      relatively isolated linear entities. In conclusion, our results provide evidence
      that AQP4 supramolecular structure is different in brain and skeletal muscle,
      which is likely to result in different tissues susceptibility to the NMO disease.

PMID- 29055084
TI  - Uneasy talking about costs of stillbirth?

PMID- 29055083
TI  - Ecosystem state shifts during long-term development of an Amazonian peatland.
AB  - The most carbon (C)-dense ecosystems of Amazonia are areas characterized by the
      presence of peatlands. However, Amazonian peatland ecosystems are poorly
      understood and are threatened by human activities. Here, we present an
      investigation into long-term ecohydrological controls on C accumulation in an
      Amazonian peat dome. This site is the oldest peatland yet discovered in Amazonia
      (peat initiation ca. 8.9 ka BP), and developed in three stages: (i) peat
      initiated in an abandoned river channel with open water and aquatic plants; (ii)
      inundated forest swamp; and (iii) raised peat dome (since ca. 3.9 ka BP). Local
      burning occurred at least three times in the past 4,500 years. Two phases of
      particularly rapid C accumulation (ca. 6.6-6.1 and ca. 4.9-3.9 ka BP),
      potentially resulting from increased net primary productivity, were seemingly
      driven by drier conditions associated with widespread drought events. The
      association of drought phases with major ecosystem state shifts (open water
      wetland-forest swamp-peat dome) suggests a potential climatic control on the
      developmental trajectory of this tropical peatland. A third drought phase centred
      on ca. 1.8-1.1 ka BP led to markedly reduced C accumulation and potentially a
      hiatus during the peat dome stage. Our results suggest that future droughts may
      lead to phases of rapid C accumulation in some inundated tropical peat swamps,
      although this can lead ultimately to a shift to ombrotrophy and a subsequent
      return to slower C accumulation. Conversely, in ombrotrophic peat domes, droughts
      may lead to reduced C accumulation or even net loss of peat. Increased surface
      wetness at our site in recent decades may reflect a shift towards a wetter
      climate in western Amazonia. Amazonian peatlands represent important carbon
      stores and habitats, and are important archives of past climatic and ecological
      information. They should form key foci for conservation efforts.

PMID- 29055085
TI  - Current use of baseline medical treatment in chronic rhinosinusitis: Data from
      the National Chronic Rhinosinusitis Epidemiology Study (CRES).
AB  - OBJECTIVES: According to clinical and comissioning guidelines for chronic
      rhinosinusitis (CRS), patients being referred to secondary care should have
      failed primary medical treatment with nasal douching (ND) and intranasal
      corticosteroids (INCS). The study objectives were to identify the rate of
      specific medical therapy in CRS patients and establish any differences in
      medication use, for both CRS and associated medical conditions, between CRS
      phenotypes. DESIGN AND SETTING: Case-control study in a secondary care setting.
      METHODS: Participant-reported study-specific questionnaire capturing free text
      data on current medication use at the time of study entry. Qualitative interviews
      with 21 participants also explored their experience of CRS and its management.
      PARTICPANTS: Patients both without (CRSsNPs) and with polyps (CRSwNPs). MAIN
      OUTCOME MEASURES: Reported use of CRS-related and non-related medications.
      RESULTS: Within a total of 1243 CRS participants, current INCS usage was low (18%
      in CRSwNPs, 12% in CRSsNPs); ND was being performed by only 1% of all
      participants. Bronchodilators and inhaled corticosteroids use was significantly
      higher in CRSwNPs participants (P < .0001). Antidepressant use was significantly
      higher in CRSsNPs (14% vs 7%, P < .0002). There were no significant regional
      variations in rates of INCS use, nor any significant influence of social
      deprivation. CONCLUSIONS: The current use of baseline medical therapy in CRS
      appears to be very low, representing a combination of poor patient compliance,
      possible ineffectiveness of treatment and a lack of familiarity with current
      guidelines amongst general practitioners and some ENT specialists. Work is needed
      to disseminate guidelines to all practitioners involved and reduce unnecessary
      burden on existing healthcare resources for this common condition by ensuring
      timely referral and definitive management.

PMID- 29055086
TI  - Acute mitogen-activated protein kinase 1/2 inhibition improves functional
      recovery and vascular changes after ischaemic stroke in rat-monitored by 9.4 T
      magnetic resonance imaging.
AB  - AIM: The aim was to evaluate the beneficial effect of early mitogen-activated
      protein kinase (MEK)1/2 inhibition administered at a clinical relevant time-point
      using the transient middle cerebral artery occlusion model and a dedicated rodent
      magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non
      invasively for 2 weeks. METHOD: Transient middle cerebral artery occlusion was
      induced in male rats for two hours followed by reperfusion. The specific MEK1/2
      inhibitor U0126 was administered ip at 6 and 24 hours post-reperfusion.
      Neurological functions were evaluated by 6- and 28-point tests. 9.4 T magnetic
      resonance imaging was used to monitor morphological infarct changes at day 2, 8
      and 14 after stroke and to evaluate cerebral perfusion at day 14.
      Immunohistochemistry evaluation of Ki67 was performed 14 days post-stroke.
      RESULTS: U0126 improved long-term behavioural outcome and significantly reduced
      infarct size. In addition, cerebral perfusion in U0126-treated animals was
      improved compared to the vehicle group. Immunohistochemistry showed a significant
      increase in Ki67+ cells in U0126-treated animals compared to the vehicle group.
      CONCLUSION: Early MEK1/2 inhibition improves long-term functional outcome,
      promotes recovery processes after stroke and most importantly provides a
      realistic time window for therapy.

PMID- 29055087
TI  - Metabolism and TAM functions-it takes two to tango.
AB  - From the evidence on clinical studies and experimental mouse models we now know
      that tumor-associated macrophages (TAMs) sustain tumor development in many
      different ways. They play a role in angiogenesis, tumor cell invasion, and
      metastasis formation. Additionally, TAMs interfere with natural killer and T-cell
      antitumoral activities, producing an immune-suppressive environment that protects
      tumor cell growth. This indicates that the tumoricidal activity of macrophages
      within the tumor microenviroment is lost due to an imbalance of the regulatory
      mechanisms underpinning these cells' function. Since metabolism is emerging as a
      major modulator of macrophage function, metabolic changes in response to signals
      coming from cancer or other immune cells might promote this imbalance, enhancing
      the tumorigenic activities of TAMs. In this review we describe the novel, most
      recent findings on how metabolism shapes TAM functions or conversely, how TAMs
      influence the activity of other cells through metabolic mechanisms. The complete
      elucidation of the metabolic switches between pro- and antitumoral properties of
      macrophages, now still in its infancy, is destined to provide scientists with new
      instruments not only to understand but also to combat cancer.

PMID- 29055089
TI  - The importance and requirement of belowground carbon inputs for robust estimation
      of soil organic carbon dynamics: Reply to Keel et al. (2017).

PMID- 29055088
TI  - The transcriptome, extracellular proteome and active secretome of agroinfiltrated
      Nicotiana benthamiana uncover a large, diverse protease repertoire.
AB  - Infiltration of disarmed Agrobacterium tumefaciens into leaves of Nicotiana
      benthamiana (agroinfiltration) facilitates quick and safe production of
      antibodies, vaccines, enzymes and metabolites for industrial use (molecular
      farming). However, yield and purity of proteins produced by agroinfiltration are
      hampered by unintended proteolysis, restricting industrial viability of the
      agroinfiltration platform. Proteolysis may be linked to an immune response to
      agroinfiltration, but understanding of the response to agroinfiltration is
      limited. To identify the proteases, we studied the transcriptome, extracellular
      proteome and active secretome of agroinfiltrated leaves over a time course, with
      and without the P19 silencing inhibitor. Remarkably, the P19 expression had
      little effect on the leaf transcriptome and no effect on the extracellular
      proteome. 25% of the detected transcripts changed in abundance upon
      agroinfiltration, associated with a gradual up-regulation of immunity at the
      expense of photosynthesis. By contrast, 70% of the extracellular proteins
      increased in abundance, in many cases associated with increased efficiency of
      extracellular delivery. We detect a dynamic reprogramming of the proteolytic
      machinery upon agroinfiltration by detecting transcripts encoding for 975
      different proteases and protease homologs. The extracellular proteome contains
      peptides derived from 196 proteases and protease homologs, and activity-based
      proteomics displayed 17 active extracellular Ser and Cys proteases in
      agroinfiltrated leaves. We discuss unique features of the N. benthamiana protease
      repertoire and highlight abundant extracellular proteases in agroinfiltrated
      leaves, being targets for reverse genetics. This data set increases our
      understanding of the plant response to agroinfiltration and indicates ways to
      improve a key expression platform for both plant science and molecular farming.

PMID- 29055091
TI  - Functional interaction of Junctophilin 2 with small- conductance Ca2+ -activated
      potassium channel subtype 2(SK2) in mouse cardiac myocytes.
AB  - AIM: Junctophilins (JPs), a protein family of the junctional membrane complex,
      maintain the close conjunction between cell surface and intracellular membranes
      in striate muscle cells mediating the crosstalk between extracellular Ca2+ entry
      and intracellular Ca2+ release. The small-conductance Ca2+ -activated K+ channels
      are activated by the intracellular calcium and play an essential role in the
      cardiac action potential profile. Molecular mechanisms of regulation of the SK
      channels are still uncertain. Here, we sought to determine whether there is a
      functional interaction of junctophilin type 2 (JP2) with the SK channels and
      whether JP2 gene silencing might modulate the function of SK channels in cardiac
      myocytes. METHODS: Association of JP2 with SK2 channel in mouse heart tissue as
      well as HEK293 cells was studied using in vivo and in vitro approaches. siRNA
      knockdown of JP2 gene was assessed by real-time PCR. The expression of proteins
      was analysed by Western blotting. Ca2+ -activated K+ current (IK,Ca ) in infected
      adult mouse cardiac myocytes was recorded using whole-cell voltage-clamp
      technique. The intracellular Ca2+ transient was measured using an IonOptix
      photometry system. RESULTS: We showed for the first time that JP2 associates with
      the SK2 channel in native cardiac tissue. JP2, via the membrane occupation and
      recognition nexus (MORN motifs) in its N-terminus, directly interacted with SK2
      channels. A colocalization of the SK2 channel with its interaction protein of JP2
      was found in the cardiac myocytes. Moreover, we demonstrated that JP2 is
      necessary for the proper cell surface expression of the SK2 channel in HEK293.
      Functional experiments indicated that knockdown of JP2 caused a significant
      decrease in the density of IK,Ca and reduced the amplitude of the Ca2+ transient
      in infected cardiomyocytes. CONCLUSION: The present data provide evidence that
      the functional interaction between JP2 and SK2 channels is present in the native
      mouse heart tissue. Junctophilin 2, as junctional membrane complex (JMC) protein,
      is an important regulator of the cardiac SK channels.

PMID- 29055093
TI  - Our best 2015-2017.

PMID- 29055090
TI  - Performance of non-traditional hyperglycemia biomarkers by chronic kidney disease
      status in older adults with diabetes: Results from the Atherosclerosis Risk in
      Communities Study.
AB  - BACKGROUND: In people with chronic kidney disease (CKD), HbA1c may be a
      problematic measure of glycemic control. Glycated albumin and fructosamine have
      been proposed as better markers of hyperglycemia in CKD. In the present study we
      investigated associations of HbA1c, glycated albumin, and fructosamine with
      fasting glucose by CKD categories. METHODS: A cross-sectional analysis was
      performed of 1665 Atherosclerosis Risk in Communities Study participants with
      diagnosed diabetes aged >=65 years. Spearman's rank correlations (r) were
      compared and Deming regression was used to obtain root mean square errors (RMSEs)
      for the associations across CKD categories defined using estimated glomerular
      filtration rate and urine albumin:creatinine ratio. RESULTS: Correlations of
      HbA1c, glycated albumin, and fructosamine with fasting glucose were lowest in
      people with severe CKD (HbA1c r = 0.52, RMSE = 0.91; glycated albumin r = 0.39,
      RMSE = 1.89; fructosamine r = 0.41, RMSE = 1.87) and very severe CKD (r = 0.48
      and RMSE = 1.01 for HbA1c; r = 0.36 and RMSE = 2.14 for glycated albumin; r =
      0.36 and RMSE = 2.22 for fructosamine). Associations of glycated albumin and
      fructosamine with HbA1c were relatively similar across CKD categories.
      CONCLUSIONS: In older adults with severe or very severe CKD, HbA1c, glycated
      albumin, and fructosamine were not highly correlated with fasting glucose. The
      results suggest there may be no particular advantage of glycated albumin or
      fructosamine over HbA1c for monitoring glycemic control in CKD.

PMID- 29055092
TI  - CROWN initiative and preterm birth prevention: researchers and editors commit to
      implement core outcome sets.

PMID- 29055094
TI  - Divergent migration within lake sturgeon (Acipenser fulvescens) populations:
      Multiple distinct patterns exist across an unrestricted migration corridor.
AB  - Population structure, distribution, abundance and dispersal arguably underpin the
      entire field of animal ecology, with consequences for regional species
      persistence, and provision of ecosystem services. Divergent migration behaviours
      among individuals or among populations are an important aspect of the ecology of
      highly mobile animals, allowing populations to exploit spatially or temporally
      distributed food and space resources. This study investigated the spatial ecology
      of lake sturgeon (Acipenser fulvescens) within the barrier free Huron-Erie
      Corridor (HEC), which connects Lake Huron and Lake Erie of the North American
      Laurentian Great Lakes. Over 6 years (2011-2016), movements of 268 lake sturgeon
      in the HEC were continuously monitored across the Great Lakes using acoustic
      telemetry (10 years battery life acoustic transmitters). Five distinct migration
      behaviours were identified with hierarchical cluster analysis, based on the
      phenology and duration of river and lake use. Lake sturgeon in the HEC were found
      to contain a high level of intraspecific divergent migration, including partial
      migration with the existence of residents. Specific behaviours included year
      round river residency and multiple lake-migrant behaviours that involved
      movements between lakes and rivers. Over 85% of individuals were assigned to
      migration behaviours as movements were consistently repeated over the study,
      which suggested migration behaviours were consistent and persistent in lake
      sturgeon. Differential use of specific rivers or lakes by acoustic-tagged lake
      sturgeon further subdivided individuals into 14 "contingents" (spatiotemporally
      segregated subgroups). Contingents associated with one river (Detroit or St.
      Clair) were rarely detected in the other river, which confirmed that lake
      sturgeon in the Detroit and St. Clair represent two semi-independent populations
      that could require separate management consideration for their conservation. The
      distribution of migration behaviours did not vary between populations, sexes,
      body size or among release locations, which indicated that intrapopulation
      variability in migratory behaviour is a general feature of the spatial ecology of
      lake sturgeon in unfragmented landscapes.

PMID- 29055095
TI  - The joint effects of major lifestyle factors on colorectal cancer risk among
      Chinese men: A prospective cohort study.
AB  - Previous studies have suggested individual healthy lifestyle factors are related
      to lower risk of colorectal cancer. Their joint effects, however, have rarely
      been investigated. We aimed to assess the combined lifestyle impact on colorectal
      cancer risk and to estimate the population attributable risks of these lifestyle
      factors. Using data from the Shanghai Men's Health Study (2002-2013), we
      constructed healthy lifestyle index composing the following lifestyle factors:
      smoking, alcohol consumption, diet, waist-hip ratio and exercise participation.
      Cox proportional hazards models were used to calculate the hazard ratios (HRs)
      and 95% confidence intervals (CIs). Over a median of 9.28 years' follow-up, 671
      colorectal cancer cases occurred (400 colon cancer and 274 rectal cancer) among
      59,503 men. Each increment of healthy lifestyle index was associated with a 17%
      lower risk of colorectal cancer (HR = 0.83, 95% CI: 0.78, 0.89), 10% of colon
      cancer (HR = 0.90, 95% CI: 0.83, 0.99) and 27% of rectal cancer (HR = 0.73, 95%
      CI: 0.66, 0.82). If all men in the cohort followed a lifestyle as defined by
      these five factors, 21% colorectal cancer cases would have been prevented (PAR =
      21%, 95% CI: 4%, 36%). In conclusion, combined lifestyle factors are
      significantly related to lower risk of colorectal cancer and the effects are more
      pronounced on rectal cancer than on colon cancer.

PMID- 29055097
TI  - Sequencing of the novel HLA-A*02:01:72 allele in a Chinese hematopoietic stem
      cell donor.
AB  - HLA-A*02:01:72 has 1 synonymous nucleotide change from HLA-A*02:01:01:01 where
      591 G is changed to A.

PMID- 29055096
TI  - An improved method for bivariate meta-analysis when within-study correlations are
      unknown.
AB  - Multivariate meta-analysis, which jointly analyzes multiple and possibly
      correlated outcomes in a single analysis, is becoming increasingly popular in
      recent years. An attractive feature of the multivariate meta-analysis is its
      ability to account for the dependence between multiple estimates from the same
      study. However, standard inference procedures for multivariate meta-analysis
      require the knowledge of within-study correlations, which are usually
      unavailable. This limits standard inference approaches in practice. Riley et al
      proposed a working model and an overall synthesis correlation parameter to
      account for the marginal correlation between outcomes, where the only data needed
      are those required for a separate univariate random-effects meta-analysis. As
      within-study correlations are not required, the Riley method is applicable to a
      wide variety of evidence synthesis situations. However, the standard variance
      estimator of the Riley method is not entirely correct under many important
      settings. As a consequence, the coverage of a function of pooled estimates may
      not reach the nominal level even when the number of studies in the multivariate
      meta-analysis is large. In this paper, we improve the Riley method by proposing a
      robust variance estimator, which is asymptotically correct even when the model is
      misspecified (ie, when the likelihood function is incorrect). Simulation studies
      of a bivariate meta-analysis, in a variety of settings, show a function of pooled
      estimates has improved performance when using the proposed robust variance
      estimator. In terms of individual pooled estimates themselves, the standard
      variance estimator and robust variance estimator give similar results to the
      original method, with appropriate coverage. The proposed robust variance
      estimator performs well when the number of studies is relatively large.
      Therefore, we recommend the use of the robust method for meta-analyses with a
      relatively large number of studies (eg, m>=50). When the sample size is
      relatively small, we recommend the use of the robust method under the working
      independence assumption. We illustrate the proposed method through 2 meta
      analyses.

PMID- 29055098
TI  - Safety of the batteries and power units used in insulin pumps: A pilot cross
      sectional study by the Association for the Study of Innovative Diabetes Treatment
      in Japan.
AB  - AIMS/INTRODUCTION: We investigated the safety of the batteries and power units
      used in insulin pumps in Japan. MATERIALS AND METHODS: A self-administered
      questionnaire was sent to the 201 members of the Association for Innovative
      Diabetes Treatment in Japan. RESULTS: A total of 56 members responded, and among
      the 1,499 active devices, 66 had episodes of trouble related to the batteries and
      power units. The ratio of reported troubles to the number of insulin pumps was
      significantly higher in insulin pumps with a continuous glucose monitoring sensor
      compared with insulin pumps without a continuous glucose monitoring sensor (odds
      ratio 2.82, P < 0.05). The cause and the consequences varied. The brands of the
      batteries varied; alkaline batteries purchased at drug stores and other shops
      accounted for 19.7%. Termination of battery life within 72 h of use was reported
      most frequently (50.0%), suspension of the insulin pump (21.2%) and leakage of
      the battery fluid (4.5%) followed. A total of 53.2% of the reported insulin pumps
      needed to be replaced, and 37.1% of them recovered after replacement of the
      battery. CONCLUSIONS: As trouble related to the batteries and power units of
      insulin pumps was frequent, practical guidance should be provided to respective
      patients regarding the use of reliable batteries, and to be well prepared for
      unexpected insulin pump failure.

PMID- 29055099
TI  - Regulation of glycosaminoglycan biogenesis is critical for sensitive-period
      dependent vocal ontogeny.
AB  - In the brain, the extracellular matrix (ECM) plays a central role during neural
      development and thus modulates critical-period regulated behavioral ontogeny. The
      major components of the ECM are glycosaminoglycans (GAGs) including chondroitin
      sulfate (CS). However, the specific roles of GAGs in behavioral development are
      largely unknown. It has been shown that xylosides affect the biological functions
      of GAGs through modulating GAG biosynthesis. Particularly, xylosides affect GAG
      biosynthesis through priming of GAG chains (priming activity), competing with
      endogenous core proteins that carry GAG initiation sites (decoy activity), or
      both. Using birdsong as our model, we investigated, for the first time, how
      xyloside-mediated modulation of GAG biogenesis affects song development.
      Xylosides infused into motor cortex of juvenile birds alter song development by
      specifically affecting ontogeny of the stereotyped sequence rather than the
      acoustic structure of syllables. Further analyses reveal that observed changes
      can be attributed to the priming activity rather than the decoy activity of
      xylosides. Collectively, these results suggest that regulation of GAG biogenesis
      through chemical biology approaches may allow promising therapeutic interventions
      of critical-period-dependent central nervous system plasticity. (c) 2017 Wiley
      Periodicals, Inc. Develop Neurobiol 77: 1401-1412, 2017.

PMID- 29055100
TI  - Optical emission of 223 Radium: in vitro and in vivo preclinical applications.
AB  - 223 Radium (223 Ra) is widely used in nuclear medicine to treat patients with
      osseous metastatic prostate cancer. In clinical practice 223 Ra cannot be imaged
      directly; however, gamma photons produced by its short-lived daughter nuclides
      can be captured by conventional gamma cameras. In this work, we show that 223 Ra
      and its short-lived daughter nuclides can be detected with optical imaging
      techniques. The light emission of 223 Ra was investigated in vitro using
      different setups in order to clarify the mechanism of light production. The
      results demonstrate that the luminescence of the 223 Ra chloride solution,
      usually employed in clinical treatments, is compatible with Cerenkov luminescence
      having an emission spectrum that is almost indistinguishable from CR one. This
      study proves that luminescence imaging can be successfully employed to detect 223
      Ra in vivo in mice by imaging whole body 223 Ra biodistribution and more
      precisely its uptake in bones.

PMID- 29055101
TI  - Substance P and dopamine interact to modulate the distribution of delta-opioid
      receptors on cholinergic interneurons in the striatum.
AB  - It has been recently demonstrated that predictive learning induces a persistent
      accumulation of delta-opioid receptors (DOPrs) at the somatic membrane of
      cholinergic interneurons (CINs) in the nucleus accumbens shell (Nac-S). This
      accumulation is required for predictive learning to influence subsequent choice
      between goal-directed actions. The current experiments investigated the local
      neurochemical events responsible for this translocation. We found that (1) local
      administration of substance P into multiple striatal sub-territories induced DOPr
      translocation and (2) that this effect was mediated by the NK1 receptor, likely
      through its expression on CINs. Interestingly, whereas intrastriatal infusion of
      the D1 agonist chloro-APB reduced the DOPr translocation on CINs and infusion of
      the D2 agonist quinpirole had no effect, co-administration of both agonists again
      generated DOPr translocation, suggesting the effect of the D1 agonist alone was
      due to receptor internalisation. In support of this, local administration of
      cocaine was found to increase DOPr translocation as was chloro-APB when co
      administered with the DOPr antagonist naltrindole. These studies provide the
      first evidence of delta-opioid receptor translocation in striatal cholinergic
      interneurons outside of the accumbens shell and suggest that, despite differences
      in local striatal neurochemical microenvironments, a similar molecular mechanism 
      involving an interaction between dopamine and SP signalling via NK1R - regulates
      DOPr translocation in multiple striatal regions. To our knowledge, this
      represents a novel mechanism by which DOPr distribution is regulated that may be
      particularly relevant to learning-induced DOPr trafficking.

PMID- 29055102
TI  - Effect of clomiphene citrate on endometrial thickness, ovulation, pregnancy and
      live birth in anovulatory women: systematic review and meta-analysis.
AB  - OBJECTIVES: To compare the impact of clomiphene citrate (CC) vs other drug
      regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live
      birth rates in women with World Health Organization (WHO) group II ovulatory
      disorders. METHODS: We searched MEDLINE, EMBASE, Scopus, Web of Science, The
      Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset
      of PubMed from inception to December 2016 and cross-checked references of
      relevant articles. We included only randomized controlled trials (RCTs) comparing
      CC used alone vs other drug regimens for ovulation induction in women with WHO
      group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live
      birth rates. We pooled weighted mean differences (WMD) with 95% confidence
      intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI
      for binary variables (ovulation, pregnancy and live birth rates). RESULTS: We
      retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction
      cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower
      in the CC group (1957 women, 3892 cycles; WMD, -1.39; 95% CI, -2.27 to -0.51; I2 
      = 100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217
      cycles; RR, 0.97; 95% CI, 0.90-1.04; I2  = 47%), while CC led to a lower
      pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63-0.95; I2  = 43%)
      and a lower live birth rate (RR, 0.70; 95% CI, 0.49-0.98; I2  = 35%). In two RCTs
      that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were
      comparable (101 women, 140 cycles; WMD, -0.23; 95% CI, -0.92 to 0.45; I2  = 78%;
      RR, 0.84; 95% CI, 0.67-1.06; I2  = 0%; and RR, 0.79; 95% CI, 0.33-1.87; I2  =
      0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT
      was lower in the CC group (340 women, 300 cycles; WMD, -1.51; 95% CI, -1.98 to 
      1.04; I2  = 45%). In two studies that compared CC with CC + nitric oxide (NO)
      donor, EMT was lower in the CC group (120 women, 304 cycles; WMD, -1.75; 95% CI, 
      2.08 to -1.41; I2  = 0%). Compared with CC plus NO donor or NAC, CC showed
      statistically significant lower ovulation and pregnancy rates. Compared with
      tamoxifen in three studies, CC showed a tendency towards lower EMT (571 women,
      844 cycles; WMD, -1.34; 95% CI, -2.70 to 0.01; I2  = 96%) with comparable
      ovulation and pregnancy rates. CONCLUSIONS: In women with WHO group II ovulatory
      disorders, ovulation induction with CC might result in lower EMT than other
      ovulation induction regimens. Whether the lower EMT caused the lower pregnancy
      and live birth rates remains to be elucidated. Letrozole seems to be beneficial
      for these women. However, our findings should be interpreted with caution as the
      quality of evidence was very low. Copyright (c) 2017 ISUOG. Published by John
      Wiley & Sons Ltd.

PMID- 29055103
TI  - Mitochondrial Ca2+ dynamics in cells and suspensions.
AB  - Mitochondria play a significant role in shaping cytosolic Ca2+ signals. Thus,
      transfer of Ca2+ across the mitochondrial membrane is much studied, not only in
      intact cells but also in artificial systems such as mitochondrial suspensions or
      permeabilised cells. Observed rates of Ca2+ changes vary by at least one order of
      magnitude. In this work, we investigate the relationship between the Ca2+
      dynamics observed in various experimental conditions using a computational model
      calibrated on experimental data. Results confirm that mitochondrial Ca2+ exchange
      fluxes through the mitochondrial Ca2+ uniporter (MCU) and the Na+ /Ca2+ exchanger
      obey the same basic kinetics in cells and in suspensions, and emphasise the
      important role played by the high Ca2+ levels reached in mitochondria-associated
      endoplasmic reticulum membranes in intact cells. Tissue specificity can be
      ascribed to the different modes of regulation of the MCU by Ca2+ , probably
      related to the specific levels of expression of the Ca2+ sensing regulator
      subunit of this channel. The model emphasises the importance of mitochondrial
      density and buffering in controlling the rate of Ca2+ exchanges with
      mitochondria, as verified experimentally. Finally, we show that heterogeneity
      between individual mitochondria can explain the large range of amplitudes and
      rates of rise in mitochondrial Ca2+ concentration that have been observed
      experimentally.

PMID- 29055104
TI  - Lifetime alcohol intake and risk of non-Hodgkin lymphoma: Findings from the
      Melbourne Collaborative Cohort Study.
AB  - Cohort studies have reported inconsistent evidence regarding alcohol intake and
      risk of non-Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close
      to study enrolment. We examined this association using alcohol intake measured
      from age 20 onwards. We calculated usual alcohol intake for 10-year periods from
      age 20 using recalled frequency and quantity of beverage-specific consumption for
      37,990 participants aged 40-69 years from the Melbourne Collaborative Cohort
      Study. Cox regression was performed to derive hazard ratios (HRs) and 95%
      confidence intervals (CIs) for the association between alcohol intake (g/day) and
      NHL risk. After a mean follow-up of 19.3 years, 538 NHL cases were diagnosed.
      Approximately 80% of participants were either lifetime abstainers or consumed
      below 20 g of ethanol/day. All categories of lifetime alcohol intake were
      associated with about 20% lower incidence of NHL compared with lifetime
      abstention, but there was no evidence of a trend by amount consumed (HR = 0.97
      per 10 g/day increment in intake, 95% CI: 0.92-1.03; p value = 0.3). HRs for
      beer, wine and spirits were 0.91 (95% CI: 0.83-1.00; p value = 0.05), 1.03 (95%
      CI: 0.94-1.12; p value = 0.6), and 1.06 (95% CI: 0.83-1.37; p value = 0.6),
      respectively, per 10 g/day increment in lifetime intake. There were no
      significant differences in associations between NHL subtypes. In this low
      drinking cohort, we did not detect a dose-dependent association between lifetime
      alcohol intake and NHL risk.

PMID- 29055105
TI  - Characteristics of chronic lymphocytic leukemia patients achieving 5+ years of
      remission after FC-based first-line treatment: Retrospective observations from
      the FILO group.

PMID- 29055106
TI  - Streptavidin-coated surfaces suppress bacterial colonization by inhibiting non
      specific protein adsorption.
AB  - Streptavidin is a 58 kDa tetrameric protein with the highest known affinity to
      biotin with a wide range of applications in bionanotechnology and molecular
      biology. Dissolved streptavidin is stable at a broad range of temperature, pH,
      proteolytic enzymes and exhibits low non-specific binding. In this study, a
      streptavidin monolayer was assembled directly on a biotinylated TiO2 -surface to
      investigate its stability against proteolytic digestion and its suppression of
      initial bacterial adsorption of Escherichia coli, Bacillus subtilis, and
      Streptococcus intermedius. In contrast to nonmodified TiO2 surfaces, streptavidin
      coated substrates showed only a negligible non-specific protein adsorption at
      physiological protein concentrations as well as a significantly reduced bacterial
      adhesion. The antiadhesive properties were demonstrated to be the main reason for
      the suppression of bacterial adhesion, which makes this approach a promising
      option for future surface biofunctionalization applications. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 758-768, 2018.

PMID- 29055108
TI  - Semi-quantitative analysis of tramadol, dextromethorphan, and metabolites in
      decomposed skeletal tissues by ultra performance liquid chromatography quadrupole
      time of flight mass spectrometry.
AB  - The use of filtration/pass-through extraction (FPTE) and ultra-performance liquid
      chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to
      detect tramadol (TRAM), dextromethorphan (DXM), and metabolites from skeletal
      remains is described. Rats (n=5) received 50 mg/kg tramadol and were euthanized
      by CO2 asphyxiation approximately 30 minutes post-dose. Rats (n=4) received 75
      mg/kg dextromethorphan and were euthanized by CO2 asphyxiation approximately 45
      minutes post-dose. Remains decomposed to skeleton outdoors and vertebral bones
      were collected. Bones were cleaned, dried, and pulverized to a fine powder. Bones
      underwent dynamic methanolic extraction followed by FPTE before analysis using
      UPLC-qTOF-MS. Recovery was at least 90% of maximal value within the first 10
      minutes of methanolic extraction for all samples assayed. Analytical response was
      measured over the concentration range of 1-500 ng/mL, with precision and bias
      <20% in triplicate analyses of all calibrators, and a limit of detection of 1
      ng/mL for TRAM, DXM, and all metabolites. The vertebral bone analyzed using this
      method detected TRAM, DXM, and their respective metabolites in all samples
      analyzed.

PMID- 29055107
TI  - Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC
      202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor
      resistance.
AB  - Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in
      numerous human malignancies, including basal cell carcinoma (BCC) and
      medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential
      effector of canonical HH/GLI signaling, show significant clinical success in BCC
      patients and have recently been approved for the treatment of advanced and
      metastatic BCC. However, rapid and frequent development of drug resistance to SMO
      inhibitors (SMOi) together with severe side effects caused by prolonged SMOi
      treatment call for alternative treatment strategies targeting HH/GLI signaling
      downstream of SMO. In this study, we report that 4SC-202, a novel clinically
      validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks
      HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH
      target gene expression in both SMOi-sensitive and -resistant cells.
      Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for
      targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in
      combination with SMOi or as second-line therapy may improve the treatment options
      for HH-associated malignancies with SMOi resistance.

PMID- 29055109
TI  - Endoscopic reduction of gastric antrum herniation through the foramen of Winslow
      into the lesser sac.

PMID- 29055110
TI  - Host conservatism, geography, and elevation in the evolution of a Neotropical
      moth radiation.
AB  - The origins of evolutionary radiations are often traced to the colonization of
      novel adaptive zones, including unoccupied habitats or unutilized resources. For
      herbivorous insects, the predominant mechanism of diversification is typically
      assumed to be a shift onto a novel lineage of host plants. However, other drivers
      of diversification are important in shaping evolutionary history, especially for
      groups residing in regions with complex geological histories. We evaluated the
      contributions of shifts in host plant clade, bioregion, and elevation to
      diversification in Eois (Lepidoptera: Geometridae), a hyper-diverse genus of
      moths found throughout the Neotropics. Relationships among 107 taxa were
      reconstructed using one mitochondrial and two nuclear genes. In addition, we used
      a genotyping-by-sequencing approach to generate 4641 SNPs for 137 taxa. Both
      datasets yielded similar phylogenetic histories, with relationships structured by
      host plant clade, bioregion, and elevation. While diversification of basal
      lineages often coincided with host clade shifts, more recent speciation events
      were more typically associated with shifts across bioregions or elevational
      gradients. Overall, patterns of diversification in Eois are consistent with the
      perspective that shifts across multiple adaptive zones synergistically drive
      diversification in hyper-diverse lineages.

PMID- 29055111
TI  - Genetic-based dissection of arsenic accumulation in maize using a genome-wide
      association analysis method.
AB  - Understanding the mechanism of arsenic (As) accumulation in plants is important
      in reducing As's toxicity to plants and its potential risks to human health.
      Here, we performed a genome-wide association study to dissect the genetic basis
      of the As contents of different maize tissues in Xixian, which was irrigated with
      As-rich surface water, and Changge using an association population consisting of
      230 representative maize inbred lines. Phenotypic data revealed a wide normal
      distribution and high repeatability for the As contents in maize tissues. The As
      concentrations in maize tissues followed the same trend in the two locations:
      kernels < axes < stems < bracts < leaves. In total, 15, 16 and 15 non-redundant
      quantitative trait loci (QTLs) associated with As concentrations were identified
      (P <= 2.04 * 10-6 ) in five tissues from Xixian, Changge, and the combination of
      the locations, respectively, explaining 9.70%-24.65% of the phenotypic variation
      for each QTL, on average. Additionally, four QTLs [involving 15 single nucleotide
      polymorphisms (SNPs)] were detected in the single and the combined locations,
      indicating that these loci/SNPs might be stable across different environments.
      The candidate genes associated with these four loci were predicted. In addition,
      four non-redundant QTLs (6 SNPs), including a QTL that was detected in multiple
      locations according to the genome-wide association study, were found to co
      localize with four previously reported QTL intervals. These results are valuable
      to understand the genetic architecture of As mechanism in maize and facilitate
      the genetic improvement of varieties without As toxicity.

PMID- 29055112
TI  - Systematic review found that there was moderate evidence that vaccinating
      healthcare workers prevented pertussis in infants.
AB  - : This systematic review investigated the effectiveness of vaccinating healthcare
      workers against pertussis on the occurrence of nosocomial pertussis outbreaks or
      infections among unprotected infants. We focused on eight studies, with five
      different study designs, that involved 39,129 healthy adolescents and adults, 115
      healthcare workers, 2000 simulated healthcare workers and a simulated population
      of 200,000 people. CONCLUSION: There was moderate evidence that tetanus
      diphtheria acellular pertussis vaccinations for healthcare workers were effective
      in preventing pertussis in all age groups and specifically in infants. The
      results must be interpreted with caution due to the low quality and heterogeneity
      of the studies.

PMID- 29055113
TI  - Accelerating patient access to novel biologics using stable pool-derived product
      for non-clinical studies and single clone-derived product for clinical studies.
AB  - Cell cloning and subsequent process development activities are on the critical
      path directly impacting the timeline for advancement of next generation therapies
      to patients with unmet medical needs. The use of stable cell pools for early
      stage material generation and process development activities is an enabling
      technology to reduce timelines. To successfully use stable pools during
      development, it is important that bioprocess performance and requisite product
      quality attributes be comparable to those observed from clonally derived cell
      lines. To better understand the relationship between pool and clone derived cell
      lines, we compared data across recent first in human (FIH) programs at Amgen
      including both mAb and Fc-fusion modalities. We compared expression and
      phenotypic stability, bioprocess performance, and product quality attributes
      between material derived from stable pools and clonally derived cells. Overall,
      our results indicated the feasibility of matching bioprocess performance and
      product quality attributes between stable pools and subsequently derived clones.
      These findings support the use of stable pools to accelerate the advancement of
      novel biologics to the clinic. (c) 2017 The Authors Biotechnology Progress
      published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical
      Engineers Biotechnol. Prog., 33:1476-1482, 2017.

PMID- 29055114
TI  - Sorafenib response in hepatocellular carcinoma: MicroRNAs as tuning forks.
AB  - Hepatocellular carcinoma (HCC) is the primary liver malignancy that contributes
      towards the second most common cause of cancer-related mortality. The targeted
      chemotherapeutic agent, sorafenib, is known to show a statistically significant
      but limited overall survival advantage in advanced HCC. However, the individual
      patient response towards sorafenib varies drastically, with most experiencing
      stable disease and few with partial response; complete response is very rare.
      Progressive disease despite the treatment is also evident in many patients,
      indicating drug resistance. These varied responses have been linked with the
      modulation of several intracellular signaling pathways. Notably, the regulation
      of these pathways through diverse operating biomolecules, including microRNAs
      (miRNAs), is the focus of recent studies. MicroRNAs are tiny, non-coding RNA
      molecules that regulate the expression of several target genes. In addition,
      miRNAs are known to play a role in the progression of HCC carcinogenesis.
      Interestingly, miRNAs have also been identified to play differential roles in
      terms of sorafenib response in HCC such as biomarkers and functional modulation
      of cellular response to sorafenib, hence, they are also being therapeutically
      evaluated. This review outlines the role of reported miRNAs in different aspects
      of sorafenib response in HCC.

PMID- 29055115
TI  - Prevalence of pre-eruptive intracoronal radiolucencies in Thai children and
      adolescents: A retrospective study.
AB  - AIM: The aim of the present study was to determine the prevalence, location,
      size, and tooth type of pre-eruptive intracoronal radiolucencies (PEIR) from
      panoramic radiographs in Thai patients. METHODS: A retrospective study of PEIR
      was conducted on 1599 panoramic radiographs of 629 Thai males and 970 Thai
      females with an age range of 4-20 years (average age: 14.0 +/- 4.0 years). Each
      radiograph was reviewed by two calibrated examiners. The age and sex of the
      patients, location, size, and tooth type of the lesions were recorded. The SPSS
      program was used for statistical analysis. RESULTS: The PEIR were found in 0.32%
      of tooth samples (29/9060) and 1.63% of patients (26/1599). There was no
      statistical difference in the presence of PEIR between both sexes. The mandibular
      second molars were the most affected teeth. The lesions were mostly located at
      the central part of the crown. The lesion sizes were mostly limited to less than
      one-third of dentinal thickness. CONCLUSIONS: The present study showed that the
      prevalence of PEIR in Thai samples is 1.63%. This could raise dentists' awareness
      in reviewing unerupted teeth in panoramic radiographs. Early detection of the
      lesions should aid in proper treatment planning of affected teeth to prevent
      complications from carious invasion after tooth eruption.

PMID- 29055117
TI  - Can neutrophil to lymphocyte ratio predict late-onset sepsis in preterm infants?
AB  - BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is an easily accessible
      biomarker that has been reported to represent disease severity in adult trials.
      The aim of this study was to evaluate the relationship between culture
      positiveness and NLR in cases where the reason of sepsis was considered, and to
      foresight an idea about the active agents. METHODS: Preterm infants with birth
      weights <=1500 g and/or <=32 gestational weeks were eligible for this study. The
      postnatal age of all included infants was more than 3 days with clinical and
      laboratory signs of sepsis. According to the results of blood cultures, all
      enrolled infants were classified into 2 groups: the culture-proven septic infants
      and suspected septic infants. The NLR was calculated as the ratio of neutrophil
      count to lymphocyte count. Initial laboratory investigations included WBC count,
      platelet count (PLT), C-reactive protein (CRP), and blood cultures. RESULTS: A
      total of 127 infants were involved: 57 culture-proven sepsis and 75 suspected
      sepsis. There were no significant differences between groups regarding
      gestational age, gender, birth weight, delivery mode, and postnatal age. Receiver
      operating curve analysis for NLR and CRP was calculated. The area under the curve
      corresponded to 0.78 +/- 0.04 (NLR) vs 0.55 +/- 0.05 (CRP). Using a cutoff point
      of 1.77 for NLR, the sensitivity was 0.73, the specificity was 0.78, and accuracy
      rate was 0.76. DISCUSSION: The prediction of NLR, an easy, inexpensive, and rapid
      method, along with CRP in the neonatal period for diagnosis of sepsis, will be
      more effective in detecting culture-proven sepsis and in decreasing unnecessary
      antibiotherapy.

PMID- 29055116
TI  - Inhaled Cryptococcus neoformans elicits allergic airway inflammation independent
      of Nuclear Factor Kappa B signalling in lung epithelial cells.
AB  - Pulmonary challenge with the ubiquitous fungus Cryptococcus neoformans results in
      allergic airway inflammation (AAI) characterized by robust recruitment of
      eosinophils and T cells producing type 2 cytokines to the lungs. Previous studies
      have demonstrated a critical role for Nuclear Factor Kappa B (NF-kappaB)
      activation within lung epithelial cells (LECs) in driving AAI in response to
      protein allergens, yet the role of LEC-intrinsic NF-kappaB in promoting AAI
      following exposure to C. neoformans is poorly understood. To investigate the role
      of LEC-intrinsic NF-kappaB in promoting AAI following C. neoformans challenge, we
      used IKK?LEC mice, which lack canonical NF-kappaB activation specifically within
      LECs. IKK?LEC and littermate control mice were intranasally challenged with 106
      CFU of C. neoformans strain 52D, and lung tissues were collected at 7, 14 and 21
      days post infection to assess the development of AAI. Notably, the absence of
      epithelial NF-kappaB signalling did not affect the magnitude or kinetics of lung
      eosinophilia when compared with the response in wild-type control mice. The total
      numbers of lung T cells producing the type 2 cytokines interleukin-5 and
      interleukin-13 were also unchanged in IKK?LEC mice. Furthermore, IKK?LEC mice
      showed no defect in the recruitment of protective interferon-gamma-producing CD4
      T cells to the lungs, fungal clearance, or host survival compared with control
      mice. Immunofluorescence imaging surprisingly revealed no evidence of nuclear
      localization of NF-kappaB in LECs in response to C. neoformans challenge,
      indicating that NF-kappaB is not activated within these cells. Taken together,
      these data strongly suggest that NF-kappaB signalling within LECs does not
      promote AAI observed in response to C. neoformans.

PMID- 29055118
TI  - Comparative efficacy and tolerability of antiemetic prophylaxis for adult highly
      emetogenic chemotherapy: A network meta-analysis of 143 randomized controlled
      trials.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is one of the commonest side
      effects among cancer patients. However, there is lacking of hierarchical
      evidences comparing different antiemetics against highly emetogenic chemotherapy.
      Therefore, we conducted a network meta-analysis to investigate their comparative
      efficacy and tolerability. Randomized controlled trials that compared different
      antiemetic categories for adult highly emetogenic chemotherapy were included
      after searching PubMed, Web of Science, Embase and Cochrane Central. Acute-phase
      no emesis and no nausea were identified as primary endpoints. We made pairwise
      and hierarchical calculations by random-effects model. Effect sizes were
      presented by odds ratio and 95% confidential interval. Subgroup analysis was
      additionally performed. 143 randomized trials were included into pooled analysis,
      containing 22,776 patients and 18 antiemetic categories. 5-HT3 RA plus
      corticosteroid plus NK-1 RA plus other (5CNO) displayed best protection against
      both acute emesis (SUCRA: 99.7%) and nausea (95.6%). 5CNO (99.7%) and 5-HT3 RA
      plus corticosteroid plus other (5CO, 85.3%) topped subgroup hierarchies for no
      naivety and anthracycline plus cyclophosphamide (AC)-based studies. On the other
      hand, 5-HT3 RA plus dopamine RA plus other (5DO) may be best fit for delayed
      emesis (92.0%) and nausea (92.7%). Subgroups featuring no-naivety and AC-based
      trials preferred 5DO (91.9%) and 5CN (88.6%), respectively. In addition, dopamine
      RA plus other (DO) had the lowest incidence of TRAE in most circumstances, except
      for AC-based subgroup where corticosteroid plus dopamine RA plus other (CDO)
      preponderated (69.2%). 5CNO and 5DO should be considered as first-line regimens
      against highly emetogenic chemotherapy induced acute and delayed CINV,
      respectively.

PMID- 29055119
TI  - Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG
      components associated with defective sensory gating in patients with Alzheimer
      disease - a two-case study.
AB  - Alzheimer's disease (AD) is associated with deterioration of memory and cognitive
      function and a degeneration of neurons of the nucleus basalis of Meynert (NBM).
      The NBM is the major input source of acetylcholine (ACh) to the cortex. The
      decreasing cholinergic innervation of the cortex due to degeneration of the NBM
      might be the cause of loss of memory function. NBM-Deep brain stimulation (NBM
      DBS) is considered to serve as a potential therapeutic option for patients with
      AD by supporting residual cholinergic transmission to stabilize oscillatory
      activity in memory-relevant circuits. However, whether DBS could improve sensory
      memory functions in patients with AD is not clear. Here, in a passive auditory
      oddball paradigm, patients with AD (N = 2) listened to repetitive background
      tones (standard tones) randomly interrupted by frequency deviants in two blocks
      with NBM-DBS OFF and then NBM-DBS ON, while age-matched healthy controls (N = 6)
      repeated the experiment twice. The mismatch negativity in NBM-DBS OFF
      significantly differed from controls in both blocks, but not under NBM-DBS, which
      was likely due to a pronounced P50 increase overlapping with the N1 in NBM-DBS
      OFF. This early complex of EEG components recovered under stimulation to a normal
      level as defined by responses in controls. In this temporal interval, we found in
      patients with NBM-DBS ON (but not with NBM-DBS OFF) and in controls a strong
      repetition suppression effect to standard tones - with more attenuated responses
      to frequently repeated standard tones. This highlights the role of NBM-DBS for
      sensory gating of familiar auditory information into sensory memory.

PMID- 29055120
TI  - The novel HLA-A*24:02 variant, HLA-A*24:02:56, identified by sequencing in a
      Chinese individual.
AB  - HLA-A*24:02:56 differs from A*24:02:01:01 by one nucleotide change at position
      795 from C to T.

PMID- 29055121
TI  - Multiple verrucous lesions of the feet in Waldenstrom macroglobulinaemia.

PMID- 29055122
TI  - Differential declines in Alaskan boreal forest vitality related to climate and
      competition.
AB  - Rapid warming and changes in water availability at high latitudes alter resource
      abundance, tree competition, and disturbance regimes. While these changes are
      expected to disrupt the functioning of boreal forests, their ultimate
      implications for forest composition are uncertain. In particular, recent site
      level studies of the Alaskan boreal forest have reported both increases and
      decreases in productivity over the past few decades. Here, we test the idea that
      variations in Alaskan forest growth and mortality rates are contingent on species
      composition. Using forest inventory measurements and climate data from plots
      located throughout interior and south-central Alaska, we show significant growth
      and mortality responses associated with competition, midsummer vapor pressure
      deficit, and increased growing season length. The governing climate and
      competition processes differed substantially across species. Surprisingly, the
      most dramatic climate response occurred in the drought tolerant angiosperm
      species, trembling aspen, and linked high midsummer vapor pressure deficits to
      decreased growth and increased insect-related mortality. Given that species
      composition in the Alaskan and western Canadian boreal forests is projected to
      shift toward early-successional angiosperm species due to fire regime, these
      results underscore the potential for a reduction in boreal productivity stemming
      from increases in midsummer evaporative demand.

PMID- 29055123
TI  - Disruption of behavior and brain metabolism in artificially reared rats.
AB  - Early adverse life stress has been associated to behavioral disorders that can
      manifest as inappropriate or aggressive responses to social challenges. In this
      study, we analyzed the effects of artificial rearing on the open field and burial
      behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism
      measured in anxiety-related brain areas. Artificial rearing of male rats was
      performed by supplying artificial milk through a cheek cannula and tactile
      stimulation, mimicking the mother's licking to rat pups from the fourth postnatal
      day until weaning. Tactile stimulation was applied twice a day, at morning and at
      night, by means of a camel brush on the rat anogenital area. As compared to
      mother reared rats, greater aggressiveness, and boldness, stereotyped behavior
      (burial conduct) was observed in artificially reared rats which occurred in
      parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos
      immunoreactivity at the amygdala and primary somatosensory cortex, and lower
      metabolism in amygdala (as measured by 2-deoxi-2-[18 fluoro]-d-glucose uptake,
      assessed by microPET imaging). These results could suggest that tactile and/or
      chemical stimuli from the mother and littermates carry relevant information for
      the proper development of the central nervous system, particularly in brain areas
      involved with emotions and social relationships of the rat. (c) 2017 Wiley
      Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017.

PMID- 29055124
TI  - Changes in hemoglobin-oxygen affinity with shape variations of red blood cells.
AB  - Shape variations of red blood cells (RBCs) are known to occur upon exposure to
      various drugs or under diseased conditions. The commonly observed discocytic RBCs
      can be transformed to echinocytic or stomatocytic shape under such conditions.
      Raman spectra of the three major shape variations, namely discocyte, echinocyte,
      and stomatocyte, of RBCs were studied while subjecting the cells to oxygenated
      and deoxygenated conditions. Analysis of the recorded spectra suggests an
      increased level of hemoglobin (Hb)-oxygen affinity for the echinocytes. Also,
      some level of Hb degradation could be noticed for the deoxygenated echinocytes.
      The effects may arise from a reduced level of intracellular adenosine
      triphosphate in echinocytic cells and an increased fraction of submembrane Hb.

PMID- 29055126
TI  - Abstracts XVII Congress of the Spanish Society of Gerodontology. Estepona, Spain,
      March 23 - 25, 2017- Meeting Abstract.

PMID- 29055125
TI  - Vascular endothelial growth factor (VEGF)-related single nucleotide polymorphisms
      rs10738760 and rs6921438 are not associated with diabetic retinopathy (DR) in
      Slovenian patients with type 2 diabetes mellitus (T2DM).
AB  - Diabetic retinopathy (DR) is a complication of diabetes characterized by vascular
      permeability, increased tissue ischemia, and angiogenesis. One of the most
      important proteins involved in angiogenesis is vascular endothelial growth factor
      (VEGF, also known as VEGFA). A previous study demonstrated that two single
      nucleotide polymorphisms (SNPs), rs6921438 and rs10738760, account for nearly
      half the variation in circulating VEGF levels. The aim of our study was to assess
      the association between rs6921438 and rs10738760 and DR in Slovenian patients
      with type 2 diabetes mellitus (T2DM). This case-control study enrolled 1037
      unrelated Slovenian individuals (Caucasians) with T2DM. DR group included 415
      T2DM patients with DR, while control group included 622 T2DM patients with no
      clinical signs of DR. The clinical and laboratory data were obtained from the
      medical records of the patients. The genotyping of rs6921438 and rs10738760 SNPs
      was carried out with real-time PCR assays. Significant differences were observed
      between patients with DR and controls in the duration of diabetes (p < 0.001),
      insulin therapy (p < 0.001), glycated hemoglobin (p = 0.001), body mass index (p
      = 0.002), total cholesterol (p = 0.002), and low-density lipoprotein cholesterol
      (p < 0.001). However, we did not observe significant differences in the genotype
      and allele distribution of the two SNPs, between DR and control group (p < 0.05).
      Logistic regression analysis showed that rs6921438 and rs10738760 were not
      independent genetic risk factors for DR in the co-dominant model adjusted for the
      above-mentioned clinical and laboratory data. In conclusion, VEGF-related SNPs
      rs10738760 and rs6921438 are not associated with DR in our group of Slovenian
      patients (Caucasians) with T2DM.

PMID- 29055127
TI  - Shoe-Floor Interactions in Human Walking With Slips: Modeling and Experiments.
AB  - Shoe-floor interactions play a crucial role in determining the possibility of
      potential slip and fall during human walking. Biomechanical and tribological
      parameters influence the friction characteristics between the shoe sole and the
      floor and the existing work mainly focus on experimental studies. In this paper,
      we present modeling, analysis, and experiments to understand slip and force
      distributions between the shoe sole and floor surface during human walking. We
      present results for both soft and hard sole material. The computational
      approaches for slip and friction force distributions are presented using a spring
      beam networks model. The model predictions match the experimentally observed sole
      deformations with large soft sole deformation at the beginning and the end stages
      of the stance, which indicates the increased risk for slip. The experiments
      confirm that both the previously reported required coefficient of friction (RCOF)
      and the deformation measurements in this study can be used to predict slip
      occurrence. Moreover, the deformation and force distribution results reported in
      this study provide further understanding and knowledge of slip initiation and
      termination under various biomechanical conditions.

PMID- 29055128
TI  - An Outflow Boundary Condition Model for Noninvasive Prediction of Fractional Flow
      Reserve in Diseased Coronary Arteries.
AB  - This paper reports on a new boundary condition formulation to model the total
      coronary myocardial flow and resistance characteristics of the myocardial
      vascular bed for any specific patient when considered for noninvasive diagnosis
      of ischemia. The developed boundary condition model gives an implicit
      representation of the downstream truncated coronary bed. Further, it is based on
      incorporating patient-specific physiological parameters that can be noninvasively
      extracted to account for blood flow demand to the myocardium at rest and
      hyperemic conditions. The model is coupled to a steady three-dimensional (3D)
      collocated pressure-based finite volume flow solver and used to characterize the
      "functional significance" of a patient diseased coronary artery segment without
      the need for predicting the hemodynamics of the entire arterial system.
      Predictions generated with this boundary condition provide a deep understanding
      of the inherent challenges behind noninvasive image-based diagnostic techniques
      when applied to human diseased coronary arteries. The overall numerical method
      and formulated boundary condition model are validated via two computational-based
      procedures and benchmarked with available measured data. The newly developed
      boundary condition is used via a designed computational methodology to (a)
      confirm the need for incorporating patient-specific physiological parameters when
      modeling the downstream coronary resistance, (b) explain the discrepancies
      presented in the literature between measured and computed fractional flow reserve
      (FFRCT), and

PMID- 29055129
TI  - Desmopressin for treating nocturia in men.
AB  - BACKGROUND: Nocturia is the bothersome symptom of awakening one or more times per
      night to void. Desmopressin is a commonly used medication for treating nocturia.
      OBJECTIVES: To assess the effects of desmopressin as compared to other
      interventions in the treatment of nocturia in men. SEARCH METHODS: We performed a
      comprehensive search of medical literature with no restrictions on the language
      of publication or publication status. The date of the latest search of all
      databases was August 2017. SELECTION CRITERIA: We included randomized or quasi
      randomized trials. Inclusion criteria were men with nocturia defined as one or
      more voids per night. Trials of children, adults with primary or secondary
      enuresis or underlying distinct disorders were excluded. DATA COLLECTION AND
      ANALYSIS: Two review authors independently classified studies and abstracted data
      from the included studies. We performed statistical analyses using a random
      effects model and interpreted data according to the Cochrane Handbook for
      Systematic Reviews of Interventions. MAIN RESULTS: We included 14 studies with
      2966 randomized men across five comparisons. Desmopressin versus placebo: based
      on short-term follow-up (up to three months), desmopressin may have a similar
      effect on the number of nocturnal voids (mean difference (MD) -0.46, 95%
      confidence interval (CI) -0.94 to 0.01; low-quality evidence). We are uncertain
      about the effect of desmopressin on major adverse events at short-term follow-up
      (risk ratio (RR) 0.97, 95% CI 0.10 to 9.03; very low-quality evidence). For
      intermediate-term follow-up (three to 12 months), desmopressin may reduce the
      number of nocturnal voids in an appreciable number of participants (MD -0.85, 95%
      CI -1.17 to -0.53; low-quality evidence). Desmopressin may result in little or no
      difference in major adverse events at intermediate-term follow-up (RR 3.05, 95%
      CI 0.13 to 73.39; low-quality evidence). We found no evidence on quality of life.
      Subgroup analyses suggest a larger effect with oral, higher-dose formulations of
      desmopressin and in men with documented nocturnal polyuria. Desmopressin versus
      behavior modification: there were no data regarding the effect on the number of
      nocturnal voids, quality of life, or major adverse events. Desmopressin versus
      alpha-blocker: based on short-term follow-up, desmopressin likely has a similar
      effect on the number of nocturnal voids (MD 0.30, 95% CI -0.20 to 0.80; moderate
      quality evidence) and quality of life (MD 0.00, 95% CI -0.35 to 0.35; moderate
      quality evidence). There were no major adverse events in either study group.
      Desmopressin plus alpha-blocker versus alpha-blocker alone: based on short-term
      follow-up, combination therapy likely results in a small, unimportant reduction
      in the number of nocturnal voids (MD -0.47, 95% CI -0.73 to -0.21; moderate
      quality evidence) and quality of life (MD -0.29, 95% CI -0.51 to -0.07; moderate
      quality evidence). The risk of major adverse events may be similar (RR 0.30, 95%
      CI 0.01 to 7.32; low-quality evidence). Desmopressin plus alpha-blocker versus
      alpha-blocker plus an anticholinergic: based on short-term follow-up, combination
      therapy likely results in little or no difference in the number of nocturnal
      voids (MD -0.43, 95% CI -0.97 to 0.11; moderate-quality evidence). We found no
      evidence on quality of life. There were no major adverse events in either study
      group. AUTHORS' CONCLUSIONS: Desmopressin may reduce the number of nocturnal
      voids in an appreciable number of participants compared to placebo in
      intermediate-term (three to 12 months) follow-up without increase in major
      adverse events. We found no evidence to compare its effects to behavior
      modification. The effect on the number of nocturnal voids is likely similar to
      that of alpha-blockers short-term with very infrequent major adverse events.
      There appears to be no added benefit in the combined use of desmopressin with an
      alpha-blocker or an anticholinergic. The findings of this review were limited by
      short-term follow-up, study limitations, and imprecision.

PMID- 29055130
TI  - Randomized trial of combined cabergoline and coasting in preventing ovarian
      hyperstimulation syndrome during in vitro fertilization/intracytoplasmic sperm
      injection cycles.
AB  - OBJECTIVE: To assess the efficacy of coasting alone, cabergoline alone, or
      combining both interventions for preventing ovarian hyperstimulation syndrome
      (OHSS) among high-risk patients undergoing in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycles.
      METHODS: The present randomized controlled trial was conducted at the IVF unit of
      a university hospital in Cairo between October 28, 2013, and July 31, 2015.
      Patients undergoing IVF/ICSI considered at risk of OHSS were randomly allocated
      to coasting, cabergoline, or combined coasting and cabergoline. The primary
      outcome was the rate and degree of symptomatically assessed OHSS. Data were
      analyzed on a per-protocol basis. RESULTS: There were 100 patients recruited to
      each group. The occurrence of early OHSS was lowest in the combination group
      compared with the other groups (P=0.002). CONCLUSION: Combining coasting and
      cabergoline was associated with a lower OHSS rate compared with either therapy
      alone. CLINICALTRIALS.GOV: NCT01984320.

PMID- 29055131
TI  - Case report of Staphylococcus epidermidis maternal sepsis and chorioamnionitis
      following fetoscopy.

PMID- 29055132
TI  - Gram-negative bacterial toe web infection - a systematic review.
AB  - Gram-negative bacterial toe web infection (GNBTWI) is a frequent therapeutic
      challenge in clinical practice with high recurrence rates and frequent need of
      systemic drugs. The aim of this systematic review was to provide an updated
      overview and evidence-based data on pathogens, risk factors and treatment of
      GNBTWI along with promoting a consistent international terminology. This
      systematic review is based on a search in PubMed database for English and German
      articles published between 1980 and 2016. A total of seven articles were
      considered appropriate for inclusion in this review regarding to treatment and
      outcome. Throughout the medical literature, a variety of terms for bacterial toe
      web infections is used. Only few data on the incidence of GNBTWI were published.
      GNBTWI has been shown to have a significant male predominance. Pseudomonas
      aeruginosa is the most commonly identified organism beside a high mixed infection
      rate. We identified the following predisposing factors: interdigital tinea,
      occlusion and humidity, history of self-medication with antifungals, antibiotics
      and glucocorticosteroids. As for treatment, debridement of macerated skin lesions
      and the hyperkeratotic rim showed good response in three published cases.
      Bacteriological workup of swabs including an antibiogram is recommended for
      identification of the proper topical and systemic therapy. Autosensitization
      dermatitis and frequent recurrences are common complications of GNBTWI. Despite
      the fact, that GNBTWI is an accepted disease entity, scarce data on GNBTWI exist
      in the medical literature. Randomized controlled trials are missing although
      needed for evidence-based therapy. To facilitate communication and exchange of
      updates of GNBTWI, we promote the suggested terminology for bacterial toe web
      diseases.

PMID- 29055133
TI  - Estimating diversification rates for higher taxa: BAMM can give problematic
      estimates of rates and rate shifts.
AB  - Estimates of diversification rates are invaluable for many macroevolutionary
      studies. Recently, an approach called BAMM (Bayesian Analysis of Macro
      evolutionary Mixtures) has become widely used for estimating diversification
      rates and rate shifts. At the same time, several articles have concluded that
      estimates of net diversification rates from the method-of-moments (MS) estimators
      are inaccurate. Yet, no studies have compared the ability of these two methods to
      accurately estimate clade diversification rates. Here, we use simulations to
      compare their performance. We found that BAMM yielded relatively weak
      relationships between true and estimated diversification rates. This occurred
      because BAMM underestimated the number of rates shifts across each tree, and
      assigned high rates to small clades with low rates. Errors in both speciation and
      extinction rates contributed to these errors, showing that using BAMM to estimate
      only speciation rates is also problematic. In contrast, the MS estimators
      (particularly using stem group ages), yielded stronger relationships between true
      and estimated diversification rates, by roughly twofold. Furthermore, the MS
      approach remained relatively accurate when diversification rates were
      heterogeneous within clades, despite the widespread assumption that it requires
      constant rates within clades. Overall, we caution that BAMM may be problematic
      for estimating diversification rates and rate shifts.

PMID- 29055134
TI  - Geographic patterns and pollination ecotypes in Claytonia virginica.
AB  - Geographical variation in pollinators visiting a plant can produce plant
      populations adapted to local pollinator environments. We documented two markedly
      different pollinator climates for the spring ephemeral wildflower Claytonia
      virginica: in more northern populations, the pollen-specialist bee Andrena
      erigeniae dominated, but in more southern populations, A. erigeniae visited
      rarely and the bee-fly Bombylius major dominated. Plants in the northern
      populations experienced faster pollen depletion than plants in southern
      populations. We also measured divergent pollen-related plant traits; plants in
      northern populations produced relatively more pollen per flower and anther
      dehiscence was more staggered than plants in southern populations. These plant
      traits might function to increase pollen dispersal via the different pollen
      vectors.

PMID- 29055135
TI  - Treatment of prurigo with methotrexate: a multicentre retrospective study of 39
      cases.
AB  - BACKGROUND: Prurigo is a common primary pruritic condition. Treatment is
      challenging. Methotrexate (MTX) is effective for the treatment of pruriginous
      dermatoses, but its use in prurigo has been little studied. OBJECTIVES: To
      investigate the efficacy and safety of MTX in the treatment of difficult-to-treat
      prurigo. METHODS: Patients from six university dermatology departments treated
      with MTX between 2006 and 2016 for difficult-to-treat prurigo (i.e. with failure
      to conventional therapies) were included in this retrospective multicentre study.
      Patients with other pruritic dermatoses were excluded. Clinical efficacy was
      recorded after 3, 6 and 12 months of treatment: (i) subjective efficacy, that is,
      evaluation of the pruritus by the patient and (ii) objective efficacy, that is,
      assessment of cutaneous lesions by the physician: complete or almost complete
      remission (CR) (healing of lesions), partial remission (PR) (incomplete
      improvement of lesions) or failure (no improvement or worsening). The overall
      response rate (ORR) included CR and PR. RESULTS: Thirty-nine patients with
      previous failure of topical steroids, H1-antihistamine drugs or phototherapy were
      included. The median weekly dose of MTX was 15 mg (range 5-25 mg). The median
      follow-up was 16 months (2-108). The mean time between onset of MTX and objective
      efficacy was 2.4 +/- 1.2 months and the mean duration of response was 19 +/- 15
      months. The ORR was 91% at 3 months [n = 36, CI 95% (81.2-100.8%), CR 44%], 94%
      at 6 months [n = 32, CI 95% (85.7-102.2%), CR 56%] and 89% at 12 months [n = 28,
      CI 95% (77.4-100.6%), CR 57%]. Seven patients stopped MTX because of failure, and
      five because of the discovery of hepatocarcinoma (n = 1), elevated transaminases
      (n = 1), infectious pneumonitis (n = 1) or gastrointestinal symptoms (n = 2).
      CONCLUSION: Methotrexate is a therapeutic option in difficult-to-treat prurigo.

PMID- 29055136
TI  - The rhinoceros among Serpents: Comparative anatomy and experimental biophysics of
      Calabar burrowing python (Calabaria reinhardtii) skin.
AB  - The Calabar burrowing python (Calabaria reinhardtii) has a unique combination of
      marked thickness of the integumentary layers, a highly organized lamellate
      arrangement of the dermal collagen bundles, and a reduction in the size of the
      interscale hinge region of the integument. Biomechanical testing demonstrates
      that the skin of C. reinhardtii is more resistant to penetration than the skin of
      other snakes. The laminar arrangement of the collagen bundles provides for
      penetrative resistance, even while maintaining the flexibility characteristic of
      snake skin. Considering the life history of this species, it is hypothesized that
      the specialized integument of C. reinhardtii is a passive defensive mechanism
      against penetrative bites from maternal rodents and predators.

PMID- 29055137
TI  - Reply to 'Topical ionic contra-viral therapy comprised of digoxin and furosemide
      as a potential novel treatment approach for common warts'.

PMID- 29055138
TI  - Effects of a bone graft substitute consisting of porous gradient HA/ZrO2 and
      gelatin/chitosan slow-release hydrogel containing BMP-2 and BMSCs on lumbar
      vertebral defect repair in rhesus monkey.
AB  - Dense biomaterial plays an important role in bone replacement. However, it fails
      to induce bone cell migration into graft material. In the present study, a novel
      bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia
      composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone
      morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared
      to repair lumbar vertebral defects. The morphological characteristics of the BGS
      evaluated by a scanning electron microscope showed that it had a three
      dimensional network structure with uniformly distributed chitosan microspheres on
      the surfaces of the graft material and the interior of the pores. Then, BGS
      (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar
      vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16
      weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed
      tomography, histomorphometry, biomechanical testing, and biochemical testing for
      bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic
      fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth
      factor, were performed to examine the reparative efficacy of the BGS and PGHC.
      The BGS displayed excellent ability to repair the lumbar vertebral defect in
      rhesus monkeys. Radiography, microcomputed tomography scanning, and
      histomorphological characterization showed that the newly formed bone volume in
      the interior of the pores in the BGS was significantly higher than in the PGHC.
      The results of biomechanical testing indicated that the vertebral body
      compression strength of the PGHC implant was lower than the other implants.
      Reverse-transcription polymerase chain reaction and western blot analyses showed
      that the expression of bone-related proteins in the BGS implant was significantly
      higher than in the PGHC implant. The BGS displayed reparative effects similar to
      autologous bone. Therefore, BGS use in vertebral bone defect repair appears
      promising.

PMID- 29055139
TI  - Exploratory study of impact of cancer-related posttraumatic stress symptoms on
      diabetes self-management among cancer survivors.
AB  - OBJECTIVE: Posttraumatic stress symptoms (PTSS) can be triggered by a diagnosis
      of a potentially life-threatening illness such as cancer. Little is known about
      the impact of cancer-related PTSS symptoms on self-management behaviors for
      comorbid chronic medical conditions such as diabetes mellitus (DM). METHODS: We
      recruited patients with DM and a recent diagnosis of early-stage cancer from 2
      medical centers in New York City. Cancer-related PTSS were assessed using the
      Impact of Events Scale (score >= 26). DM self-management behaviors (medication
      adherence, exercise, healthy diet, and glucose testing) were measured 3 months
      later. Logistic regression was used to assess the association between cancer
      related PTSS symptoms and DM self-management behaviors, adjusting for gender,
      marital status, and anxiety symptoms. RESULTS: Of 56 participants recruited, 33%
      reported cancer-related PTSS symptoms. Elevated cancer-related PTSS symptoms were
      associated with lack of healthy diet (odds ratio: 0.08, 95% confidence interval:
      0.01-0.62). CONCLUSIONS: Early-stage cancer survivors with cancer-related PTSS
      symptoms were less likely to adhere to some DM self-management behaviors.
      Providers should recognize the impact of cancer-related PTSS symptoms to better
      support comorbid disease management in cancer survivors.

PMID- 29055140
TI  - Morphological analysis of the male reproductive accessory glands of the bat
      Artibeus lituratus (Phyllostomidae: Chiroptera).
AB  - Bats are distributed worldwide from tropical to temperate regions. Despite their
      wide geographical radiation and advances in studies using evolutionary
      approaches, aspects related to the reproduction of these animals remain poorly
      explored, especially those related to the male reproductive accessory glands
      (RAGs). Thus, the aim of this study was to analyze the morphophysiology of the
      male RAGs in the bat Artibeus lituratus. The RAGs in A. lituratus are composed of
      a compact intra-abdominal glandular complex, consisting of the prostate with two
      prostatic regions (ventral and dorsal), plus Littre glands and a pair of extra
      abdominal bulbourethral glands. The ventral region of the prostate has an
      epithelium with variable morphology, due to its holocrine type of secretion. In
      contrast, the dorsal region has a typical cubic-to-columnar pseudostratified
      epithelium. Both regions contain two cell types, basal and secretory cells.
      Similar to the epithelial morphology, the secretion also varies, with the ventral
      region containing numerous PAS-positive globular vesicles, whereas the dorsal
      region has a more fluid, hyaline and PAS-negative secretion. Littre glands are
      dispersed in the connective tissue of the urethra, while the bulbourethral glands
      are located in the penile root, both glands with cubic-to-columnar
      pseudostratified epithelium and globular PAS-positive secretion. The results
      demonstrate that the RAGs of A. lituratus are composed of two prostatic regions,
      ventral and dorsal, and urethral and bulbourethral glands, with no seminal
      vesicles. Each prostatic region has unique and distinctive characteristics, with
      the ventral region presenting an exclusive holocrine nature and the dorsal region
      having similarities to the ventral prostate of rodents.

PMID- 29055141
TI  - Novel mutations in the LRP5 gene in patients with Osteoporosis-pseudoglioma
      syndrome.

PMID- 29055142
TI  - The fate of the bone graft in cerebrospinal fluid rhinorrhea endoscopic repair
      for idiopathic intracranial hypertension: a retrospective case series analysis.
AB  - INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a common cause of
      spontaneous cerebrospinal fluid (CSF) leaks necessitating surgical intervention,
      and grafting of septal, mastoid, or turbinate bone over the defect is
      increasingly performed to strengthen the repair of the primary defect. However,
      the postoperative fate of these grafted bone fragments is largely unknown.
      METHODOLOGY: We performed a retrospective study of patients at the University of
      Pennsylvania undergoing repair of spontaneous CSF leaks secondary to IIH.
      Preoperative and postoperative CTs were analyzed to determine the integration
      status of the transplanted bone. RESULTS: Fourteen patients with IIH and
      spontaneous CSF leak were analyzed, with a mean postoperative imaging follow-up
      period of four years. Thirteen patients (93%) had bone present on CT imaging,
      with 11 of these patients displaying evidence of bone integration. Two patients
      (14%) had a recurrent CSF leak in the same area, including the patient with
      absence of bone on imaging follow-up. CONCLUSIONS: Bone grafts frequently
      incorporate when used for repair of spontaneous CSF leaks associated with IIH.
      The rate of incorporation is comparable to bone grafts used for other etiologies
      of CSF leak, despite the increased pressure on the repair site. Any rigid repair
      of the leak site should likely be accompanied by treatment of the underlying
      intracranial hypertension to avoid leak recurrence.

PMID- 29055143
TI  - Pasireotide for the treatment of refractory hypoglycaemia from malignant
      insulinoma.

PMID- 29055144
TI  - Increased prevalence of diabetes mellitus in bullous pemphigoid patients during
      the last decade.

PMID- 29055145
TI  - Positive predictive values of peripheral arterial and venous thrombosis codes in
      French hospital database.
AB  - French hospital database, called Programme de Medicalisation des Systemes
      d'Information (PMSI), covers all hospital stays in France (>66 million
      inhabitants). The aim of this study was to estimate the positive predictive
      values (PPVs) of primary diagnosis codes of peripheral arterial and venous
      thrombosis codes in the PMSI, encoded with the International Classification of
      Diseases, 10th revision. Data were extracted from the PMSI database of Toulouse
      University Hospital, south of France. We identified all the hospital stays in
      2015 with a code of peripheral arterial or venous thrombosis as primary
      diagnosis. We randomly selected 100 stays for each category of thrombosis and
      reviewed the corresponding medical charts. The PPV of peripheral arterial
      thrombosis codes was 83.0%, 95% confidence interval (CI): 73.9-89.1, and the PPV
      of correct location of thrombosis was 81.0%, 95% CI: 72.2-87.5. The PPV of
      pulmonary embolism was 99.0%, 95% CI: 93.8-99.9. The PPV of peripheral venous
      thrombosis was 95.0%, 95% CI: 88.2-98.1, and the PPV of correct location of
      thrombosis was 85.0%, 95% CI: 76.7-90.7. Primary diagnoses of peripheral arterial
      and venous thrombosis demonstrated good PPVs in the PMSI.

PMID- 29055146
TI  - Association between natural killer cell activity and the risk of colorectal
      neoplasia.
AB  - BACKGROUND AND AIM: Low activity of natural killer (NK) cells is known to be
      associated with higher risk of cancer, especially with poor prognosis and the
      presence of colorectal cancer (CRC). We investigated whether NK cells activity
      differs between subjects with and without colorectal neoplasia (CRN). METHODS: A
      cross-sectional study was performed on 1818 asymptomatic examinees aged >= 30
      years who underwent NK cell activity test (which quantitates the amount of
      interferon-gamma secreted into the plasma by NK cells) and a colonoscopy as part
      of a health checkup. RESULTS: The mean age of the study population was 41.4
      years. The proportion of overall CRN and advanced CRN was 13.5% (n = 246) and
      0.7% (n = 13), respectively. Only one subject was diagnosed with CRC. The median
      level of NK cell activity was lower in subjects with CRN than in those without
      CRN (1205 vs 1515 pg/mL, P = 0.009). It was also lower in subjects with non
      advanced CRN than in those without CRN (1221 vs 1515 pg/mL; P = 0.036). Moreover,
      it was lower in subjects with advanced CRN than in those with non-advanced CRN
      (480 vs 1221 pg/mL; P = 0.028). Subjects with low levels of NK cell activity (<
      250 pg/mL) had a higher prevalence of overall CRN (19.0% vs 12.9%, P = 0.024) and
      advanced CRN (3.4% vs 0.4%, P = 0.001) than those who demonstrated higher level
      (>= 250 pg/mL). CONCLUSIONS: Natural killer cell activity seemed to decrease
      along with CRC progression toward the later stages in the adenoma-carcinoma
      sequence. Its activity may be depressed in relation to progression of neoplasia,
      even at precancerous stage.

PMID- 29055147
TI  - Cognitive function among long-term survivors of heart transplantation.
AB  - BACKGROUND: Cognitive impairment is documented early after heart transplantation
      (HTx), but we lack data on cognitive function beyond the fourth year post
      transplant. Against the background of good long-term survival, this knowledge is
      necessary to improve clinical care throughout the entire post-transplant period.
      METHODS: We assessed cognitive function with a neuropsychological test battery in
      a sample of HTx recipients >=16 years post-transplant. To improve clinical
      utility, we also applied adapted consensus criteria for Mild Cognitive Impairment
      (MCI). Furthermore, we explored sociodemographic and clinical characteristics
      possibly related to cognitive function. RESULTS: Thirty-seven subjects were
      included 20.3 (+/-3.8) years after HTx. Mean age was 57.5 (+/-14.2) years, and
      18.9% were women. Up to 38.9% exhibited impaired test performance (ie,
      performance at least 1.5 standard deviations below the normative mean) on several
      individual cognitive measures, especially on measures of processing speed,
      executive functions, memory, and language functions. One subject was diagnosed
      with dementia, and 30.1% qualified for MCI. Those with MCI had lower hemoglobin
      than those without. CONCLUSIONS: A substantial proportion of long-term survivors
      of HTx might be cognitively impaired. The level of impairment appears comparable
      to what is defined as MCI in the literature. Modifiable factors related to
      cognitive impairment might exist.

PMID- 29055148
TI  - Trends in health-care costs and utilization for inflammatory bowel disease from
      2010 to 2014 in Korea: A nationwide population-based study.
AB  - BACKGROUND AND AIM: Data regarding health-care costs and utilization for
      inflammatory bowel disease (IBD) at the population level are limited in Asia. We
      aimed to investigate the nationwide prevalence and health-care cost and
      utilization of IBD in Korea. METHODS: We tracked the IBD-attributable health-care
      costs and utilization from 2010 to 2014 using the public dataset obtained from
      Korean National Health Insurance Service claims. We estimated the nationwide
      prevalence of IBD using population census data from Statistics Korea during the
      same period. RESULTS: In total, 236 106 IBD patients were analyzed. The estimated
      IBD prevalence significantly increased from 85.1/100 000 in 2010 to 106/100 000
      in 2014. The overall annual health-care costs for IBD increased from $23.2
      million (US dollars) in 2010 to $49.7 million in 2014 (P < 0.001). During the
      same period, the health-care cost per capita also increased from $572.3 to $983.7
      (P < 0.001). The outpatient to total cost ratio increased from 45.5% in 2010 to
      66.6% in 2014. Regarding health-care utilization, the outpatient to total days of
      service use ratio increased from 73.1% in 2010 to 76.9% in 2014. Of the total
      days of service used, the proportions of tertiary, general, and community
      hospitals increased significantly with a concomitant decrease in that of primary
      clinics (all P values < 0.001). CONCLUSIONS: This population-based study
      confirmed the steadily rising rate of prevalence of IBD in Korea. It also
      demonstrated that the shifting to outpatient care and advanced care settings are
      drivers for the dramatic increase in IBD-related health-care costs in Korea.

PMID- 29055149
TI  - The implementation of knowledge dissemination in the prevention of occupational
      skin diseases.
AB  - BACKGROUND: Occupational skin diseases (OSD) have a high medical, social,
      economic and political impact. Knowledge dissemination from research activities
      to key stakeholders involved in health care is a prerequisite to make prevention
      effective. OBJECTIVES: To study and prioritize different activity fields and
      stakeholders that are involved in the prevention of OSD, to reflect on their
      inter-relationships, to develop a strategic approach for knowledge dissemination
      and to develop a hands-on tool for OSD prevention projects METHODS: Seven
      different activity fields that are relevant in the prevention of OSD have been
      stepwise identified. This was followed by an impact analysis. Fifty-five
      international OSD experts rated the impact and the influence of the activity
      fields for the prevention of OSD with a standardized questionnaire. RESULTS:
      Activity fields identified to have a high impact in OSD prevention are the
      political system, mass media and industry. The political system has a strong but
      more indirect effect on the general population via the educational system, local
      public health services or the industry. The educational system, mass media,
      industry and local public health services have a strong direct impact on the OSD
      'at risk' worker. Finally, a hands-on tool for future OSD prevention projects has
      been developed that addresses knowledge dissemination and different stakeholder
      needs. CONCLUSION: Systematic knowledge dissemination is important to make OSD
      prevention more effective and to close the gap between research and practice.
      This study provides guidance to identify stakeholders, strategies and
      dissemination channels for systematic knowledge dissemination which need to be
      adapted to country-specific structures, for example the social security system
      and healthcare systems. A key for successful knowledge dissemination is building
      linkages among different stakeholders, building strategic partnerships and
      gaining their support right from the inception phase of a project.

PMID- 29055150
TI  - Distinct sources of gene flow produce contrasting population genetic dynamics at
      different range boundaries of a Choristoneura budworm.
AB  - Populations are often exposed to multiple sources of gene flow, but accounts are
      lacking of the population genetic dynamics that result from these interactions or
      their effects on local evolution. Using a genomic clines framework applied to
      1,195 single nucleotide polymorphisms, we documented genomewide, locus-specific
      patterns of introgression between Choristoneura occidentalis biennis spruce
      budworms and two ecologically divergent relatives, C. o. occidentalis and
      Choristoneura fumiferana, that it interacts with at alternate boundaries of its
      range. We observe contrasting hybrid indexes between the two hybrid zones, no
      overlap in "gene-flow outliers" (clines showing relatively extreme extents or
      rates of locus-specific introgression) and variable linkage disequilibrium among
      those outliers. At the same time, correlated genomewide rates of introgression
      between zones suggest the presence of processes common to both boundaries. These
      findings highlight the contrasting population genetic dynamics that can occur at
      separate frontiers of a single population, while also suggesting that shared
      patterns may frequently accompany cases of divergence-with-gene-flow that involve
      a lineage in common. Our results point to potentially complex evolutionary
      outcomes for populations experiencing multiple sources of gene flow.

PMID- 29055151
TI  - Prevention and management of spouting bleeding during endoscopic submucosal
      dissection for large subpedunculated-type colonic tumor.

PMID- 29055152
TI  - Predominance of regorafenib over sorafenib: Restoration of membrane-bound MICA in
      hepatocellular carcinoma cells.
AB  - BACKGROUND AND AIM: The multi-kinase inhibitor regorafenib (REG) was recently
      demonstrated to be effective in patients with sorafenib (SOR)-resistant
      hepatocellular carcinoma (HCC). Interestingly, SOR is known to enhance the
      accumulation of membrane-bound MHC class I polypeptide-related sequence A (mMICA)
      in HCC cells and to block the production of soluble MICA (sMICA), an
      immunological decoy. In addition, MICA is associated with HCC in patients with
      chronic hepatitis C. We have now compared the impact of REG and SOR on MICA in
      HCC cells, as well as the immunotherapeutic implications thereof. METHODS: HepG2
      and PLC/PRF/5 cells were exposed to REG and SOR, and levels of sMICA and mMICA
      were measured by ELISA and flow cytometry, respectively. The drugs were also
      tested in vitro for inhibitory activity against recombinant human A disintegrin
      and metalloprotease 9 (ADAM9), a sheddase that releases MICA from the membrane.
      RESULTS: To a greater extent than SOR, but without marked difference in
      cytotoxicity, REG significantly suppressed mRNA and protein expression of ADAM9
      and ADAM10, thereby decreasing production of sMICA and boosting accumulation of
      mMICA. Accumulation of mMICA in response to REG was reversed by siRNA against
      ADAM9. However, the drugs did not inhibit the enzymatic activity of ADAM9 in
      vitro. CONCLUSIONS: The clinical superiority of REG over SOR is partially
      attributable to reduced MICA shedding via transcriptional suppression of ADAM9
      and ADAM10.

PMID- 29055153
TI  - Defining the actinic keratosis field: a literature review and discussion.
AB  - Despite the chronic and increasingly prevalent nature of actinic keratosis (AK)
      and existing evidence supporting assessment of the entire cancerization field
      during clinical management, a standardized definition of the AK field to aid in
      the understanding and characterization of the disease is lacking. The objective
      of this review was to present and appraise the available evidence describing the
      AK cancerization field, with the aim of determining a precise definition of the
      AK field in terms of its molecular (including genetic and immunological),
      histological and clinical characteristics. Eight European dermatologists
      collaborated to conduct a review and expert appraisal of articles detailing the
      characteristics of the AK field. Articles published in English before August 2016
      were identified using PubMed and independently selected for further assessment
      according to predefined preliminary inclusion and exclusion criteria. In
      addition, a retrospective audit of patients with AK was performed to define the
      AK field in clinical terms. A total of 32 review articles and 47 original
      research articles provided evidence of sun-induced molecular (including genetic
      and immunological) and histological skin changes in the sun-exposed area affected
      by AK. However, the available literature was deemed insufficient to inform a
      clinical definition of the AK field. During the retrospective audit, visible
      signs of sun damage in 40 patients with AK were assessed. Telangiectasia, atrophy
      and pigmentation disorders emerged as 'reliable or very reliable' indicators of
      AK field based on expert opinion, whereas 'sand paper' was deemed a 'moderately
      reliable' indicator. This literature review has revealed a significant gap of
      evidence to inform a clinical definition of the AK field. Therefore, the authors
      instead propose a clinical definition of field cancerization based on the
      identification of visible signs of sun damage that are reliable indicators of
      field cancerization based on expert opinion.

PMID- 29055154
TI  - Gene expression changes in male accessory glands during ageing are accompanied by
      reproductive decline in Drosophila melanogaster.
AB  - Senescence is accompanied by loss of reproductive functions. Here, we studied
      reproductive ageing in Drosophila melanogaster males and asked whether the
      expected decline in male reproductive success is due to diminished functionality
      of the male accessory gland (AG). The male AG produces the majority of seminal
      fluid proteins (SFPs) transferred to the female at mating. SFPs induce female
      postmating changes and are key to male reproductive success. We measured age
      dependent gene expression changes for five representative SFP genes in males from
      four different age groups ranging from 1 to 6 weeks after eclosion.
      Simultaneously, we also measured male reproductive success in postmating traits
      mediated by transfer of these five SFPs. We found a decreased in male SFP gene
      expression with advancing age and an accompanying decline in male postmating
      success. Hence, male reproductive senescence is associated with a decline in
      functionality of the male AG. While overall individual SFP genes decreased in
      expression, our results point towards the idea that the composition of an
      ejaculate might change with male age as the rate of change was variable for those
      five genes.

PMID- 29055155
TI  - Apremilast for the treatment of moderate-to-severe palmoplantar psoriasis:
      results from a double-blind, placebo-controlled, randomized study.
AB  - BACKGROUND: Palmoplantar psoriasis is a variant of psoriasis vulgaris which can
      severely impair quality of life. OBJECTIVES: The main objectives of this double
      blind, placebo-controlled, randomized study were to assess the efficacy and
      impact on quality of life and work productivity of apremilast for the treatment
      of moderate-to-severe palmoplantar psoriasis. METHODS: A total of 100 patients
      with moderate-to-severe palmoplantar psoriasis were randomized to either
      apremilast 30 mg bid or placebo for 16 weeks. At Week 16, all patients received
      apremilast 30 mg bid until Week 32. The primary endpoint was the proportion of
      patients who achieved a Palmoplantar Psoriasis Physician Global Assessment
      (PPPGA) of 0/1 at Week 16. RESULTS: There was no significant difference in the
      proportion of patients who achieved a PPPGA of 0/1 at Week 16 between patients
      randomized to apremilast (14%) and placebo (4%; P = 0.1595). After 32 weeks of
      treatment with apremilast, 24% of patients achieved a PPGA of 0/1. In addition,
      apremilast was superior to placebo in achieving Palmoplantar Psoriasis Area
      Severity Index (PPPASI) 75 (apremilast: 22%; placebo: 8%; P = 0.0499), in
      improving PPPASI (apremilast: -7.4 +/- 7.1; placebo: -3.6 +/- 5.9; P = 0.0167),
      Dermatology Life Quality Index score (apremilast: -4.3 +/- 5.1; placebo: -0.8 +/-
      4.5; P = 0.0004) and in reducing activity impairment (apremilast: -11.0 +/- 22.3;
      placebo: 2.5 +/- 25.5; P = 0.0063). CONCLUSION: Despite the absence of a
      significant difference between apremilast and placebo in proportion of patients
      achieving a PPPGA of 0/1, the presence of significant differences observed for
      several secondary endpoints suggests that apremilast may have a role in the
      treatment of moderate-to-severe palmoplantar psoriasis.

PMID- 29055156
TI  - Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve
      gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter
      scores.
AB  - AIMS: The comparative efficacy of Roux-en-Y gastric bypass (RYGB) and sleeve
      gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear.
      The DiaRem diabetes remission prediction score uses HbA1c , age and diabetes
      medications but not diabetes duration. The aim of this study was to compare the
      DiaRem with the DiaBetter score that includes diabetes duration, upon combined
      (complete plus partial) 2-year post-surgery diabetes remission in people
      following RYGB and sleeve gastrectomy, and to investigate the relationship
      between weight loss and diabetes remission. METHODS: A retrospective single
      centre cohort study of obese people with diabetes who underwent RYGB (107) or
      sleeve gastrectomy (103) and a validation cohort study (173) were undertaken.
      Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under
      receiving operator characteristic (ROC) curves were calculated. The relationship
      between % weight loss and diabetes remission was investigated using logistic
      regression. RESULTS: The proportion of people achieving diabetes remission was
      highest for those with the lowest DiaBetter and DiaRem scores. Areas under the
      ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817-0.916); DiaRem: 0.865
      (95%CI: 0.814-0.915), P=0.856]. Two-year % weight loss was higher post RYGB [26.6
      (95%CI: 24.8-28.4)] vs post-sleeve gastrectomy [20.6 (95%CI: 18.3-22.8),
      P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12
      5.60), P=0.025]. This association became non-significant when adjusted for %
      weight loss. CONCLUSION: DiaBetter and DiaRem scores predict diabetes remission
      following both procedures. Two-year % weight loss plays a key role in determining
      diabetes remission.

PMID- 29055157
TI  - Simulating the onset of spring vegetation growth across the Northern Hemisphere.
AB  - Changes in the spring onset of vegetation growth in response to climate change
      can profoundly impact climate-biosphere interactions. Thus, robust simulation of
      spring onset is essential to accurately predict ecosystem responses and feedback
      to ongoing climate change. To date, the ability of vegetation phenology models to
      reproduce spatiotemporal patterns of spring onset at larger scales has not been
      thoroughly investigated. In this study, we took advantage of phenology
      observations via remote sensing to calibrate and evaluated six models, including
      both one-phase (considering only forcing temperatures) and two-phase (involving
      forcing, chilling, and photoperiod) models across the Northern Hemisphere between
      1982 and 2012. Overall, we found that the model that integrated the photoperiod
      effect performed best at capturing spatiotemporal patterns of spring phenology in
      boreal and temperate forests. By contrast, all of the models performed poorly in
      simulating the onset of growth in grasslands. These results suggest that the
      photoperiod plays a role in controlling the onset of growth in most Northern
      Hemisphere forests, whereas other environmental factors (e.g., precipitation)
      should be considered when simulating the onset of growth in grasslands. We also
      found that the one-phase model performed as well as the two-phase models in
      boreal forests, which implies that the chilling requirement is probably fulfilled
      across most of the boreal zone. Conversely, two-phase models performed better in
      temperate forests than the one-phase model, suggesting that photoperiod and
      chilling play important roles in these temperate forests. Our results highlight
      the significance of including chilling and photoperiod effects in models of the
      spring onset of forest growth at large scales, and indicate that the
      consideration of additional drivers may be required for grasslands.

PMID- 29055158
TI  - A phase 2a randomized controlled study to evaluate the pharmacokinetic, safety,
      tolerability and clinical effect of topically applied Umeclidinium in subjects
      with primary axillary hyperhidrosis.
AB  - BACKGROUND: Hyperhidrosis is a common medical condition which can have a
      significant impact on quality of life. Umeclidinium (UMEC) is a long-acting
      muscarinic antagonist (LAMA) developed as a dermal formulation. OBJECTIVES: This
      2-week, double-blind, randomized, vehicle-controlled study evaluated systemic
      exposure, safety and tolerability of topically administered UMEC in subjects with
      primary axillary hyperhidrosis. Clinical effect was a secondary objective,
      measured by gravimetry and the hyperhidrosis disease severity scale (HDSS).
      Vehicle was included to evaluate safety. METHODS: Twenty-three subjects were
      randomized to either 1.85% UMEC (N = 18) or vehicle (N = 5) once daily. RESULTS:
      Measurable plasma concentrations were observed in 78% of subjects after the
      treatment. Nine subjects (50%) on UMEC and two subjects (40%) on vehicle reported
      AEs, most commonly application site reactions. At Day 15, seven subjects (41%) in
      UMEC and two subjects (40%) in vehicle had at least a 50% reduction in sweat
      production. Eight subjects (47%) in UMEC and one subject (20%) in vehicle had at
      least a two-point reduction in HDSS. No comparisons of treatment arms were
      planned prospectively. CONCLUSIONS: The measurable exposure, acceptable safety
      and preliminary clinical activity observed in this proof-of-concept study suggest
      the potential clinical utility of topical UMEC in subjects with axillary
      hyperhidrosis.

PMID- 29055159
TI  - Genomics of natural populations: Evolutionary forces that establish and maintain
      gene arrangements in Drosophila pseudoobscura.
AB  - The evolution of complex traits in heterogeneous environments may shape the order
      of genes within chromosomes. Drosophila pseudoobscura has a rich gene arrangement
      polymorphism that allows one to test evolutionary genetic hypotheses about how
      chromosomal inversions are established in populations. D. pseudoobscura has >30
      gene arrangements on a single chromosome that were generated through a series of
      overlapping inversion mutations with >10 inversions with appreciable frequencies
      and wide geographic distributions. This study analyses the genomic sequences of
      54 strains of Drosophila pseudoobscura that carry one of six different
      chromosomal arrangements to test whether (i) genetic drift, (ii) hitchhiking with
      an adaptive allele, (iii) direct effects of inversions to create gene disruptions
      caused by breakpoints, or (iv) indirect effects of inversions in limiting the
      formation of recombinant gametes are responsible for the establishment of new
      gene arrangements. We found that the inversion events do not disrupt the
      structure of protein coding genes at the breakpoints. Population genetic analyses
      of 2,669 protein coding genes identified 277 outlier loci harbouring elevated
      frequencies of arrangement-specific derived alleles. Significant linkage
      disequilibrium occurs among distant loci interspersed between regions with low
      levels of association indicating that distant allelic combinations are held
      together despite shared polymorphism among arrangements. Outlier genes showing
      evidence of genetic differentiation between arrangements are enriched for sensory
      perception and detoxification genes. The data presented here support the indirect
      effect of inversion hypothesis where chromosomal inversions are favoured because
      they maintain linked associations among multilocus allelic combinations among
      different arrangements.

PMID- 29055160
TI  - Temperature and soil fertility as regulators of tree line Scots pine growth and
      survival-implications for the acclimation capacity of northern populations.
AB  - The acclimation capacity of leading edge tree populations is crucially important
      in a warming climate. Theoretical considerations suggest that adaptation through
      genetic change is needed, but this may be a slow process. Both positive and
      catastrophic outcomes have been predicted, while empirical studies have lagged
      behind theory development. Here we present results of a 30-year study of 55,000
      Scots pine (Pinus sylvestris) trees, planted in 15 common gardens in three
      consecutive years near and beyond the present Scots pine tree line. Our results
      show that, contrary to earlier predictions, even long-distance transfers to the
      North can be successful when soil fertility is high. This suggests that present
      northern populations have a very high acclimation capacity. We also found that
      while temperature largely controls Scots pine growth, soil nutrient availability
      plays an important role-in concert with interpopulation genetic variation-in
      Scots pine survival and fitness in tree line conditions. These results suggest
      that rapid range expansions and substantial growth enhancements of Scots pine are
      possible in fertile sites as seed production and soil nutrient mineralization are
      both known to increase under a warming climate. Finally, as the ontogenetic
      pattern of tree mortality was highly site specific and unpredictable, our results
      emphasize the need for long-term field trials when searching for the factors that
      control fitness of trees in the variable edaphic and climatic conditions of the
      far North.

PMID- 29055161
TI  - Does intranasal instillation TiO2 cause pulmonary tumorigenesis in male mice?

PMID- 29055162
TI  - Evaluation of inter-individual differences in gut bacterial isoflavone
      bioactivation in humans by PCR-based targeting of genes involved in equol
      formation.
AB  - AIM: To identify human subjects harbouring intestinal bacteria that bioactivate
      daidzein to equol using a targeted PCR-based approach. METHODS AND RESULTS: In a
      pilot study including 17 human subjects, equol formation was determined in faecal
      slurries. In parallel, faecal DNA was amplified by PCR using degenerate primers
      that target highly conserved regions of dihydrodaidzein reductase and
      tetrahydrodaidzein reductase genes. PCR products of the expected size were
      observed for six of the eight subjects identified as equol producers. Analysis of
      clone libraries revealed the amplification of sequences exclusively related to
      Adlercreutzia equolifaciens in four of the subjects tested positive for equol
      formation, whereas in three of the equol producers, only sequences related to
      Slackia isoflavoniconvertens were observed. No amplicons were obtained for one
      equol-forming subject, thus suggesting the presence of nontargeted alternative
      genes. Amplicons were only sporadically observed in the nonequol producers.
      CONCLUSION: The majority of human subjects who produced equol were also detected
      with the developed PCR-based approach. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      obtained results shed light on the distribution and the diversity of known equol
      forming bacterial species in the study group and indicate the presence of as yet
      unknown equol-forming bacteria.

PMID- 29055163
TI  - Microbial sensor for drug susceptibility testing of Mycobacterium tuberculosis.
AB  - AIMS: Drug susceptibility testing (DST) of clinical isolates of Mycobacterium
      tuberculosis is critical in treating tuberculosis. We demonstrate the possibility
      of using a microbial sensor to perform DST of M. tuberculosis and shorten the
      time required for DST. METHODS AND RESULTS: The sensor is made of an oxygen
      electrode with M. tuberculosis cells attached to its surface. This sensor
      monitors the residual oxygen consumption of M. tuberculosis cells after treatment
      with anti-TB drugs with glycerine as a carbon source. In principle, after drug
      pretreatment for 4-5 days, the response differences between the sensors made of
      drug-sensitive isolates are distinguishable from the sensors made of drug
      resistant isolates. The susceptibility of the M. tuberculosis H37Ra strain, its
      mutants and 35 clinical isolates to six common anti-TB drugs: rifampicin,
      isoniazid, streptomycin, ethambutol, levofloxacin and para-aminosalicylic acid
      were tested using the proposed method. The results agreed well with the gold
      standard method (LJ) and were determined in significantly less time. The whole
      procedure takes approximately 11 days and therefore has the potential to inform
      clinical decisions. CONCLUSIONS: To our knowledge, this is the first study that
      demonstrates the possible application of a dissolved oxygen electrode-based
      microbial sensor in M. tuberculosis drug resistance testing. This study used the
      microbial sensor to perform DST of M. tuberculosis and shorten the time required
      for DST. SIGNIFICANCE AND IMPACT OF THE STUDY: The overall detection result of
      the microbial sensor agreed well with that of the conventional LJ proportion
      method and takes less time than the existing phenotypic methods. In future
      studies, we will build an O2 electrode array microbial sensor reactor to enable a
      high-throughput drug resistance analysis.

PMID- 29055164
TI  - Reflectance confocal microscopy identification of subclinical basal cell
      carcinomas during and after vismodegib treatment.
AB  - BACKGROUND: Recently, it has been shown that reflectance confocal microscopy
      (RCM) could identify subclinical basal cell carcinoma (BCC) during vismodegib
      treatment of locally advanced BCC. OBJECTIVES: To evaluate specificity and
      sensitivity of clinical, dermoscopic and RCM examination for BCC in patients with
      multiple BCCs treated by vismodegib. METHODS: Ninety four BCCs had 710 clinical,
      dermoscopic and RCM examinations during 72 weeks of vismodegib treatment. Thirty
      eight were biopsied at the end of the treatment. Sensitivity and specificity for
      these 38 lesions were calculated. BCC diagnoses of clinical, dermoscopic and RCM
      examination on all the 710 investigations were compared using chi-square test.
      RESULTS: Reflectance confocal microscopy was extremely more sensitive than
      dermoscopy and clinical examination and slightly less specific (sensitivity of
      95%, 35% and 33% and specificity of 81%, 88% and 86% for RCM, dermoscopy and
      clinical examination, respectively) for the identification of residual BCC in the
      38 biopsied cases. Considering all the 710 observations, RCM correctly diagnosed
      more BCCs than dermoscopy and clinical examination. CONCLUSION: Reflectance
      confocal microscopy is a non-invasive technique that can detect subclinical
      residual BCC during and after vismodegib treatment helping the clinician to
      identify incomplete tumour regression.

PMID- 29055165
TI  - Development of tripe palms and soles in a patient with long pre-existing systemic
      mastocytosis and newly developed non-small cell lung cancer.

PMID- 29055166
TI  - Drug monitoring of sunitinib in patients with advanced solid tumors: a
      monocentric observational French study.
AB  - Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies.
      Data are sparse to evaluate its impact on treatment management. This study aimed
      to determine a threshold value of plasma drug exposure associated with the
      occurrence of grade 3-4 toxicity, then the potential impact of TDM on clinical
      decision. Consecutive outpatients treated with sunitinib were prospectively
      monitored between days 21 and 28 of the first cycle, then monthly until disease
      progression. At each consultation, the composite AUCT,ss (sunitinib + active
      metabolite SU12662) was assayed. The decisions taken during each consultation
      were matched with AUCT,ss and compared to the decisional algorithm based on TDM.
      A total of 105 cancer patients and 288 consultations were matched with the
      closest AUCT,ss measurement. The majority (60%) of the patients had metastatic
      renal clear-cell carcinoma (mRCC). Fifty-five (52%) patients experienced grade 3
      4 toxicity. Multivariate analysis identified composite AUCT,ss as a parameter
      independently associated with grade 3-4 toxicity (P < 0.0001). Using the ROC
      curve, the threshold value of composite AUCT,ss predicting grade >=3 toxicity was
      2150 ng/mL/h (CI 95%, 0.6-0.79%; P < 0.0001). At disease progression in patients
      with mRCC, AUCT,ss tended to be lower than the one assayed during the first cycle
      (1678 vs. 2004 ng/mL/h, respectively, P = 0.072). TDM could have changed the
      medical decision for sunitinib dosing in 30% of patients at the first cycle of
      treatment, and in 46% of the patients over the whole treatment course. TDM is
      routinely feasible and may both contribute to improve toxicity management and to
      identify sunitinib underexposure at the time of disease progression.

PMID- 29055167
TI  - Genomic differentiation and patterns of gene flow between two long-tailed tit
      species (Aegithalos).
AB  - Patterns of heterogeneous genomic differentiation have been well documented
      between closely related species, with some highly differentiated genomic regions
      ("genomic differentiation islands") spread throughout the genome. Differential
      levels of gene flow are proposed to account for this pattern, as genomic
      differentiation islands are suggested to be resistant to gene flow. Recent
      studies have also suggested that genomic differentiation islands could be
      explained by linked selection acting on genomic regions with low recombination
      rates. Here, we investigate genomic differentiation and gene-flow patterns for
      autosomes using RAD-seq data between two closely related species of long-tailed
      tits (Aegithalos bonvaloti and A. fuliginosus) in both allopatric and contact
      zone populations. The results confirm recent or ongoing gene flow between these
      two species. However, there is little evidence that the genomic regions that were
      found to be highly differentiated between the contact zone populations are
      resistant to gene flow, suggesting that differential levels of gene flow is not
      the cause of the heterogeneous genomic differentiation. Linked selection may be
      the cause of genomic differentiation islands between the allopatric populations
      with no or very limited gene flow, but this could not account for the
      heterogeneous genomic differentiation between the contact zone populations, which
      show evidence of recent or ongoing gene flow.

PMID- 29055168
TI  - Long-term safety of growth hormone-A combined registry analysis.
AB  - OBJECTIVES: Preliminary data from the French cohort of the Safety and
      Appropriateness of Growth hormone treatments in Europe (SAGhE) study raised
      concerns regarding the safety of recombinant human GH, suggesting that GH may
      increase mortality and incidence of stroke in patients treated during childhood
      for GH deficiency or short stature. We evaluated published safety data, focusing
      on mortality, neoplasms, cerebrovascular events and diabetes across a number of
      large-scale pharmaceutical company GH registries. DESIGN: A literature review was
      conducted using PubMed, EMBASE and Google Scholar to identify all relevant safety
      data from manufacturers' GH registries published between 1988 and April 2016.
      Results were hand-sorted to exclude nonrelevant publications; bibliographic
      references from retrieved articles were evaluated for any additional references.
      RESULTS: The published data do not support an increased risk of mortality in
      children or adults treated with GH. There was no evidence of an increased risk of
      stroke, new malignancy, leukaemia, nonleukaemic extracranial tumours or
      recurrence of intracranial malignancy in patients without risk factors. The risk
      of a second neoplasm is increased, particularly if patients have received
      radiation therapy for a central nervous system tumour. There may be an increased
      risk of type 2 diabetes in GH-treated patients, but this appears to be confined
      to those with pre-existing risk factors. CONCLUSIONS: Patients with risk factors
      for malignancy or type 2 diabetes should be treated with caution and monitored
      during follow-up, but current published data provide reassurance on the long-term
      safety profile of GH in patients receiving GH treatment.

PMID- 29055169
TI  - Diversification in tropics and subtropics following the mid-Miocene climate
      change: A case study of the spider genus Nesticella.
AB  - Caves may offer suitable refugia for troglophilic invertebrates during periods of
      unfavourable climatic conditions because of their stable microclimates. As a
      consequence, allopatric divergence from their epigean counterparts may occur,
      leading to formation of truly hypogean communities (the Climatic Relict
      Hypothesis). Unlike the well-studied effects of Pleistocene glaciations, we know
      little about how ancient climate changes drove the development of cave-dwelling
      organisms living at both middle and lower latitudes. We investigate the
      evolutionary history of the troglophilic spider genus Nesticella (Araneae,
      Nesticidae) in relation to Asian Neogene (23-2.6 Ma) climatic changes. Our
      analyses discern clear differences in the evolution of the two main clades of
      Nesticella, which occur in temperate/subtropical and tropical latitudes. Eastern
      Asian Nesticella gradually evolved greater sedentariness and a strict
      subterranean lifestyle starting from the middle Miocene Epoch (~15-14 Ma) in
      conjunction with the progressive deterioration of the climate and vegetational
      shifts. Caves appear to have acted as refugia because of their internally uniform
      temperature and humidity, which allowed these spiders to survive increasing
      external seasonality and habitat loss. In contrast, a uniform accumulation of
      lineages, long-lasting times for dispersals and the lack of a comparable habitat
      shifting characterized the tropical lineage. This difference in pattern likely
      owes to the mild effects of climate change at low latitudes and the consequent
      lack of strong climatic drivers in tropical environments. Thus, the mid-Miocene
      climatic shift appears to be the major evolutionary force shaping the ecological
      differences between Asian troglophilic invertebrates and the driver of the
      permanent hypogean communities in middle latitudes.

PMID- 29055170
TI  - Global climate change increases risk of crop yield losses and food insecurity in
      the tropical Andes.
AB  - One of the greatest current challenges to human society is ensuring adequate food
      production and security for a rapidly growing population under changing climatic
      conditions. Climate change, and specifically rising temperatures, will alter the
      suitability of areas for specific crops and cultivation systems. In order to
      maintain yields, farmers may be forced to change cultivation practices, the
      timing of cultivation, or even the type of crops grown. Alternatively, farmers
      can change the location where crops are cultivated (e.g., to higher elevations)
      to track suitable climates (in which case the plants will have to grow in
      different soils), as cultivated plants will otherwise have to tolerate warmer
      temperatures and possibly face novel enemies. We simulated these two last
      possible scenarios (for temperature increases of 1.3 degrees C and 2.6 degrees C)
      in the Peruvian Andes through a field experiment in which several traditionally
      grown varieties of potato and maize were planted at different elevations (and
      thus temperatures) using either the local soil or soil translocated from higher
      elevations. Maize production declined by 21%-29% in response to new soil
      conditions. The production of maize and potatoes declined by >87% when plants
      were grown under warmer temperatures, mainly as a result of the greater incidence
      of novel pests. Crop quality and value also declined under simulated migration
      and warming scenarios. We estimated that local farmers may experience severe
      economic losses of up to 2,300 US$ ha-1  yr-1 . These findings reveal that
      climate change is a real and imminent threat to agriculture and that there is a
      pressing need to develop effective management strategies to reduce yield losses
      and prevent food insecurity. Importantly, such strategies should take into
      account the influences of non-climatic and/or biotic factors (e.g., novel pests)
      on plant development.

PMID- 29055171
TI  - Safer and healthier reduced nitrites turkey meat sausages using lyophilized
      Cystoseira barbata seaweed extract.
AB  - Background Nitrite salts are still common additives in the meat industry. The
      present study provides a first approach on the employment of the lyophilized
      aqueous extract (WE) of the Tunisian seaweed Cystoseira barbata for the quality
      enhancement of turkey meat sausage. Methods WE was supplemented as a natural
      antioxidant agent to investigate its effectiveness in delaying lipid oxidation
      turkey meat sausages containing reduced amounts of sodium nitrites. Results On
      storage day 5, all concentrations of WE (0.01-0.4 %) reduced the meat lipid
      oxidation by approximately 36 %, as compared to the negative control containing
      only 80 mg/kg of meat of sodium nitrites as antioxidant. It was noted that within
      15 days of refrigerated storage, a meat system containing 80 mg/kg of meat of
      sodium nitrites and 0.02 % and 0.04 % of WE had similar Thiobarbituric Acid
      Reactive Substances (TBARS) levels (19+/-1.32 and 17+/-1.12 umol/kg of meat,
      respectively), which were comparable to the positive control containing sodium
      nitrites (150 mg/kg of meat) and 0.045 % vitamin C (18.46+/-1.27 umol/kg of
      meat). In-depth, the metabolomic profiling using gas chromatography-mass
      spectrometry (GC/MS) and liquid chromatography-quadripole-time-of-flight-mass
      spectrometry (LC-QTOF-MS) analyses of the Tunisian seaweed C. barbata solvent
      extracts showed that the main active compounds were phenolic compounds, fatty
      acids and sterols. Conclusions Overall, the cold medium containing C. barbata
      lyophilized aqueous extrac, with strong antioxidant activity and antihypertensive
      properties, may open the way to the development of a natural quality enhancement
      strategy for new functional and ever healthier reduced nitrites meat sausages
      based on algae.

PMID- 29055172
TI  - Evaluation of the antioxidant impact of ginger-based kombucha on the murine
      breast cancer model.
AB  - Background Abnormal metabolism is a common event in cancerous cells. For example,
      the increase of reactive oxygen species (ROS) production, particularly due to
      aerobic respiration during invasive stage, results in cancer progression. Herein,
      the impact of kombucha tea prepared from ginger on the alteration of antioxidant
      agents was assessed in the breast cancer animal model. Methods Two types of
      kombucha tea with or without ginger were administered to BALB/c mice before and
      after tumor challenge. Superoxide dismutase (SOD), catalase, glutathione (GSH)
      and malondialdehyde (MDA) were evaluated in tumor, liver and kidney. Results
      Administration of kombucha ginger tea significantly decreased catalase activity
      as well as GSH and MDA level in tumor homogenate (p<0.001). A significant
      decrease in SOD activity and increase in MDA quantity was determined in the
      kidney which had received kombucha ginger tea (p<0.01). Conclusions The
      consumption of kombucha prepared from ginger could exert minor antioxidant
      impacts by balancing multi antioxidant factors in different tissues in the breast
      cancer models.

PMID- 29055173
TI  - Safety and efficacy of the cervical pessary combined with vaginal progesterone
      for the prevention of spontaneous preterm birth.
AB  - INTRODUCTION: The aim of this study was to evaluate the safety and efficacy of
      the combined treatment of cervical pessary and endovaginal progesterone for the
      prevention of spontaneous preterm birth (SPB) in women with a short cervical
      length (CL) between 20 and 24 weeks of gestation. MATERIALS AND METHODS: This is
      a prospective study of women with a singleton pregnancy and a sonographically
      detected mid-trimester CL <=25 mm. The primary outcome measure was spontaneous
      delivery before 34 weeks (238 days) of gestation. RESULTS: The study sample
      consisted of 90 women with a mean CL of 14.2 mm (SD=6.5 mm). Of the women, 34.4%
      had at least one risk factor for SPB; 7.8% delivered preterm before 34 weeks of
      gestation, and 25.6%, before 37 weeks. Neonatal death occurred in two (2.2%)
      cases due to respiratory distress syndrome. Lower body mass index values, history
      of preterm delivery and number of second trimester miscarriages were
      independently associated with delivery before 34 weeks. CONCLUSION: The
      combination of vaginal progesterone and cervical pessary for the prevention of
      SPB in women with a short cervix is safe and well tolerated. This therapy was
      associated with pregnancy prolongation, reduced prematurity rate and a low rate
      of perinatal complications.

PMID- 29055174
TI  - Maternal outcomes in first and second trimester termination of pregnancy: which
      are the risk factors?
AB  - AIMS: To evaluate maternal complications of first trimester and second trimester
      termination of pregnancy (TOP) performed after first or second trimester positive
      prenatal diagnosis (PD). RESULTS: We performed a retrospective study from January
      2007 to December 2011, on 844 patients, who underwent a TOP after positive
      amniocentesis or chorionic villus sampling (CVS) for foetal aneuploidies,
      performed for maternal age >=35 years of age, positive prenatal screening (PS) or
      for genetic reasons. Exclusions criteria were gestational age >22+0 weeks, twin
      pregnancy and co-existing maternal pathologies. We compared maternal
      complications of first trimester and second trimester TOP and we established
      which risk factors were correlated to higher maternal complications
      (haemorrhages, transfusion, repeated uterine curettage and infections). Maternal
      complications were significantly higher in second trimester TOP. Previous uterine
      surgery is a significant risk factor for maternal complications in second
      trimester TOP, but not in first trimester TOP. Six uterine ruptures and three
      hysterectomies occurred, all in multiparous women with second trimester TOP. All
      uterine ruptures occurred in women with previous caesarean sections. CONCLUSIONS:
      First trimester TOP in women with risks factors for maternal complications
      guarantees better maternal outcomes and less health costs. Thus, in these women
      we should prefer a first trimester PS and PD.

PMID- 29055175
TI  - Pregnancy after malignant disease - challenges and possibilities.

PMID- 29055176
TI  - Preterm labor and preterm birth.

PMID- 29055177
TI  - Pesticide management approach towards protecting the safety and health of farmers
      in Southeast Asia.
AB  - BACKGROUND: It is estimated that pesticide production and use have increased
      continuously in the countries of Southeast Asia in recent years. Within the
      context of protecting the safety and health of workers in the agricultural
      sector, there is an existing gap in the implementation of the pesticide
      management framework because safety and health effects arising from occupational
      exposures continue to be reported. OBJECTIVE: This study aims to provide
      narrative similarities, differences and weaknesses of the existing pesticide
      management system in Southeast Asian countries (Brunei, Cambodia, Indonesia,
      Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam) within the
      context of occupational safety and health. METHODS: This is preliminary
      traditional review study. Pesticide regulation and management at the country
      level were identified using web-based search engines such as Scopus,
      ScienceDirect, PubMed and Google. Book, reports, legislation document and other
      documents retrieved were also gathered from international organizations and
      specific websites of governmental agency in Southeast Asian countries. The scope
      of this review is only limited to literature written in English. In total, 44
      review articles, reports and documents were gathered for this study. The approach
      of pesticide management in protecting safety and health in the agricultural
      setting were benchmarked according to the elements introduced by the United
      States Environmental Protection Agency, namely, (1) the protection of workers and
      (2) the practice of safety. RESULTS: All countries have assigned a local
      authority and government organization to manage and control pesticide use in the
      agricultural sector. The countries with the highest usage of pesticide are
      Thailand, Philippines and Malaysia. Most Southeast Asian countries have
      emphasized safety practice in the management of pesticide usage, but there were
      less emphasis on the element of protection of workers within the framework in
      Indonesia, Myanmar, Thailand and Vietnam. CONCLUSION: The governing bodies in the
      countries of Southeast Asia have placed significant effort to develop framework
      related to pesticide management at the country level. The implementation of
      pesticide management based on the existing framework is evident in most of the
      countries but needs to be improved. It is suggested that emphasis be given to the
      implementation of diagnosis, health surveillance and reporting system as well as
      following or adopting standard guidelines for the protection of workers in terms
      of safety and health in the agricultural sector.

PMID- 29055178
TI  - N-Acetylborrelidin B: a new bioactive metabolite from Streptomyces mutabilis sp.
      MII.
AB  - In the course of our screening program for new bioactive compounds, a naturally
      new 18-membered macrolide antibiotic, N-acetylborrelidin B (1) along with
      borrelidin (2) were obtained from the marine Streptomyces mutabilis sp. MII. The
      strain was isolated from a sediment sample collected in the Red Sea at the
      Hurghada Coast and characterized taxonomically. Additional nine diverse bioactive
      compounds were reported: 6-prenyl-indole-3-acetonitrile (3), sitosteryl-3beta-d
      glucoside, campesterol, ferulic acid, linoleic acid methyl ester, linoleic acid,
      N-acetylanthranilic acid, indole 3-acetic acid methyl ester, indole 3-carboxylic
      acid, and adenosine. Structure 1 was confirmed by in-depth NMR studies and by
      mass spectra, and comparison with related literature data. The antimicrobial
      activity of the strain extract and compounds 1 and 2 were studied using a panel
      of pathogenic microorganisms. The in vitro cytotoxicity of compounds 1 and 2 as
      well as the crude extract were tested against the human cervix carcinoma cell
      line (KB-3-1).

PMID- 29055179
TI  - Nigella Sativa Oil Protects the Rat Ovary from Oxidative Injury Due to Ischemia
      Reperfusion.
AB  - BACKGROUND The aim of this study was to evaluate the effects of Nigella sativa
      (N. sativa) oil (NSO) on ovarian oxidative damage following ischemia-reperfusion
      injury, using a rat model of ovarian torsion. MATERIAL AND METHODS Forty-eight
      female albino Wistar rats were divided into six groups: (Group 1) laparotomy
      only; (Group 2) intraperitoneal NSO (2 ml/kg), 1 hour following laparotomy;
      (Group 3) 3 hours of ovarian ischemia; (Group 4) 3 hours of ovarian ischemia
      followed by 3 hours of reperfusion; (Group 5) 3 hours of ovarian ischemia and 2
      ml/kg of NSO 1 hour before laparotomy; (Group 6) 3 hours of reperfusion after 3
      hours of ovarian ischemia and 2 ml/mg of NSO 1 hour before laparotomy. RESULTS
      The antioxidant status, ceruloplasmin level, native thiol, total thiol, and
      disulfide levels of the control group (Group 1) were significantly increased
      compared with the ovarian ischemia-reperfusion group treated with NSO (Group 6)
      (p=0.003, p=0.002, p=0.006, p=0.001 and p=0.003, respectively); these levels in
      the ovarian ischemia group (Group 3) and ischemia-reperfusion group (Group 4)
      were statistically similar to those of the ovarian ischemia + NSO group (Group 5)
      and ovarian ischemia-reperfusion + NSO group (Group 6). CONCLUSIONS In this
      preliminary rat study, administration of NSO shortly after the onset of ovarian
      ischemia-reperfusion injury, did not significantly reduce levels of markers of
      oxidative injury. Further studies are required to evaluate the ovarian changes at
      the tissue level, and to determine the optimum dose of NSO.

PMID- 29055180
TI  - Artificial Photosynthetic Systems for CO2 Reduction: Progress on Higher
      Efficiency with Cobalt Complexes as Catalysts.
AB  - The conversion of CO2 into fuels or value-added chemicals is currently a field of
      great research interest. Molecular cobalt catalysts have long been used as
      mediators of reductive transformations of CO2 . In this Minireview, the cobalt
      complex-based photocatalytic and photoelectrocatalytic systems for CO2 reduction
      are discussed and summarized, alongside progress on the design of new molecular
      cobalt catalysts and their performance in photocatalysis.

PMID- 29055181
TI  - PFA-100-measured aspirin resistance is the predominant risk factor for
      hospitalized cardiovascular events in aspirin-treated patients: A 5-year cohort
      study.
AB  - WHAT IS KNOWN AND OBJECTIVE: Aspirin therapy is the clinical gold standard for
      the prevention of cardiovascular events. However, cardiovascular events still
      develop in some patients undergoing aspirin therapy. Many laboratory methods
      exist for measuring aspirin resistance. Using the platelet Function Analyzer
      (PFA)-100 system, we aimed to determine the effect of aspirin resistance on
      hospitalized cardiovascular events (hCVE) in a 5-year follow-up cohort. We also
      sought to determine the impact of aspirin resistance on the relationship between
      common cardiovascular risk factors and cardiovascular hospitalization. METHOD:
      Aspirin resistance was evaluated in aspirin-treated patients from the outpatient
      department. A total of 465 patients during a 5-year follow-up period were
      included in this study. The primary endpoint of the study was hospitalization for
      any acute cardiovascular event. The prevalence and associated risk factors of
      acute cardiovascular events were evaluated. RESULTS AND DISCUSSION: Aspirin
      resistance was prevalent in 91 (20.0%) of 465 patients. Prior hospitalization
      history of cardiovascular events was highly associated with aspirin resistance (P
      = .001). At the 5-year follow-up, cardiovascular events were found to have
      developed in 11 patients (8 stroke and 3 myocardial infarction) who exhibited
      aspirin resistance (12.1%) and in 9 (4 stroke and 5 myocardial infarction)
      patients who did not exhibit aspirin resistance (2.4%) (P < .001). At the 5-year
      follow-up, multivariate logistic regression analysis results showed a strong
      association between aspirin resistance and cardiovascular events (adjusted odds
      ratio 4.28; 95% CI: 1.64-11.20; P = .03). WHAT IS NEW AND CONCLUSION: PFA-100
      measurements of aspirin resistance correlate with hCVE, as evidenced by both the
      past medical history and the 5-year follow-up. The logistic regression analysis
      results showed that aspirin resistance plays a larger role in hospitalized
      cardiovascular disease than do other cardiovascular risk factors.

PMID- 29055183
TI  - Democracy and health: Evidence from within-country heterogeneity in the Congo.
AB  - The literature documents a positive association between democracy and health, and
      studies supporting this claim have largely relied on cross-country panel
      analyses. In many developing countries, however, local traditional leaders at the
      micro-level play a key role in individuals' daily lives while the influence of
      the national government is largely negligible. In response, this study revisits
      the relationship between democracy and health using micro-level household data
      from 816 randomly selected villages in Eastern Congo. We find little or no
      evidence that health outcomes are better in villages that are governed by elected
      leaders compared to villages where leaders are not elected. Our data suggest that
      efforts to improve health outcomes in this setting may need to focus on issues
      such as gender discrimination and education.

PMID- 29055182
TI  - Computational drug repositioning for rare diseases in the era of precision
      medicine.
AB  - There are tremendous unmet needs in drug development for rare diseases.
      Computational drug repositioning is a promising approach and has been
      successfully applied to the development of treatments for diseases. However, how
      to utilize this knowledge and effectively conduct and implement computational
      drug repositioning approaches for rare disease therapies is still an open issue.
      Here, we focus on the means of utilizing accumulated genomic data for
      accelerating and facilitating drug repositioning for rare diseases. First, we
      summarize the current genome landscape of rare diseases. Second, we propose
      several promising bioinformatics approaches and pipelines for computational drug
      repositioning for rare diseases. Finally, we discuss recent regulatory incentives
      and other enablers in rare disease drug development and outline the remaining
      challenges.

PMID- 29055184
TI  - Predict protein structural class by incorporating two different modes of
      evolutionary information into Chou's general pseudo amino acid composition.
AB  - Structural class is an important attribute of protein, which plays an important
      role in both the experiment and theoretical research of protein science.
      Prediction of protein structural classes has been a challenging task,
      specifically for low-similarity datasets. In this paper, we develop a feature
      extraction method PSSS-SOMA-PSSM by incorporating two different modes of
      evolutionary information into Chou's general pseudo amino acid composition
      (PseAAC) based on predicted secondary structure sequence (PSSS) and position
      specific scoring matrix (PSSM). We construct a 170-dimensional (170D) feature
      vector for each protein sequence sample, which contains 10D PSSS features that
      reflect content, alternating word frequency and novel position information, and
      contains 160D PSSM features that are calculated by second-order moving average
      (SOMA) algorithm. The SVM classifier with RBF kernel function and the jackknife
      test are used to predict and evaluate on 1189, 25PDB and 640 datasets with
      sequence similarity lower than 40%, 25%, and 25%, respectively. Comparison of our
      results with other methods shows that the proposed method provides the state-of
      the-art performance and a cost-effective alternative to structural classes
      prediction for low-similarity datasets.

PMID- 29055185
TI  - Effect of the solvent on the conformational behavior of the alanine dipeptide
      deduced from MD simulations.
AB  - In general, peptides do not exhibit a well-defined conformational profile in
      solution. However, despite the experimental blurred picture associated with their
      structure, compelling spectroscopic evidence shows that peptides exhibit local
      order. The conformational profile of a peptide is the result of a balance between
      intramolecular interactions between different atoms of the molecule and
      intermolecular interactions between atoms of the molecule and the solvent.
      Accordingly, the conformational profile of a peptide will change upon the
      properties of the solvent it is soaked. To get insight into the balance between
      intra- and intermolecular interactions on the conformational preferences of the
      peptide backbone we have studied the conformational profile of the alanine
      dipeptide in diverse solvents using molecular dynamics as sampling technique.
      Solvents studied include chloroform, methanol, dimethyl sulfoxide, water and N
      methylacetamide. Different treatments of the solvent have been studied in the
      present work including explicit solvent molecules, a generalized Born model and
      using the bulk dielectric constant of the solvent. The diverse calculations
      identify four major conformations with different populations in the diverse
      solvents: the C7eq only sampled in chloroform; the C5 or extended conformation;
      the polyproline (PII) conformation and the right-handed alpha-helix conformation
      (alphaR). The results of present calculations permit to analyze how the balance
      between intra- and intermolecular interactions explains the populations of the
      diverse conformations observed.

PMID- 29055186
TI  - Designed inhibitors with hetero linkers for gastric proton pump H+,K+-ATPase:
      Steered molecular dynamics and metadynamics studies.
AB  - Acid suppressant SCH28080 and its derivatives reversibly reduce acid secretion
      activity of the H+,K+-ATPase in a K+ competitive manner. The results on
      homologation of the SCH28080 by varying the linker chain length suggested the
      improvement in efficacy. However, the pharmacokinetic studies reveal that the
      hydrophobic nature of the CH2 linker units may not help it to function as a
      better acid suppressant. We have exploited the role of linker unit to enhance the
      efficacy of such reversible acid suppressant drug molecules using hetero linker,
      i.e., disulfide and peroxy linkers. The logarithm of partition coefficient
      defined for a drug molecule relates to the partition coefficient, which allows
      the optimum solubility characteristics to reach the active site. The logarithm of
      partition coefficient calculated for the designed inhibitors suggests that
      inhibitors would possibly reach the active site in sufficient concentration like
      in the case of SCH28080. The steered molecular dynamics studies have revealed
      that the Inhibitor-1 with disulfide linker unit is more stable at the active site
      due to greater noncovalent interactions compared to the SCH28080. Centre of mass
      distance analysis suggests that the Cysteine-813 amino acid residue selectively
      plays an important role in the inhibition of H+,K+-ATPase for Inhibitor-1.
      Furthermore, the quantum chemical calculations with M11L/6-31+G(d,p) level of
      theory have been performed to account the noncovalent interactions responsible
      for the stabilization of inhibitor molecules in the active site gorge of the
      gastric proton pump at different time scale. The hydrogen bonding and hydrophobic
      interaction studies corroborate the center of mass distance analysis as well.
      Well-tempered metadynamics free energy surface and center of mass separation
      analysis for the Inhibitor-1 is in good agreement with the steered molecular
      dynamics results. The torsional angle of the linker units seems to be crucial for
      better efficacy of drug molecules. The torsional angle of linker units of
      SCH28080 (COCH2C) and of Inhibitor 1 (CSSC) prefers to lie within ~60 degrees -90
      degrees  for a longer time during the simulations, whereas, the peroxy linker
      (COOC) of Inhibitor 2 prefers to adopt ~120-160 degrees . Therefore, it appears
      that the smaller torsion angle of linker units can achieve better interactions
      with the active site residues of H+,K+-ATPase to inhibit the acid secretion
      activity. The reversible drug molecules with disulfide linker unit would be a
      promising candidate as proton pump antagonist to H+,K+-ATPase.

PMID- 29055188
TI  - Healthcare investment and income inequality.
AB  - This paper examines how the relative shares of public and private health
      expenditures impact income inequality. We study a two period overlapping
      generation's growth model in which longevity is determined by both private and
      public health expenditure and human capital is the engine of growth. Increased
      investment in health, reduces mortality, raises return to education and affects
      income inequality. In such a framework we show that the cross-section earnings
      inequality is non-decreasing in the private share of health expenditure. We test
      this prediction empirically using a variable that proxies for the relative
      intensity of investments (private versus public) using vaccination data from the
      National Sample Survey Organization for 76 regions in India in the year 1986-87.
      We link this with region-specific expenditure inequality data for the period 1987
      2012. Our empirical findings, though focused on a specific health investment
      (vaccines), suggest that an increase in the share of the privately provided
      health care results in higher inequality.

PMID- 29055187
TI  - An effective HIV-1 integrase inhibitor screening platform: Rationality validation
      of drug screening, conformational mobility and molecular recognition analysis for
      PFV integrase complex with viral DNA.
AB  - As an important target for the development of novel anti-AIDS drugs, HIV-1
      integrase (IN) has been widely concerned. However, the lack of a complete
      accurate crystal structure of HIV-1 IN greatly blocks the discovery of novel
      inhibitors. In this work, an effective HIV-1 IN inhibitor screening platform,
      namely PFV IN, was filtered from all species of INs. Next, the 40.8% similarity
      with HIV-1 IN, as well as the high efficiency of virtual screening and the good
      agreement between calculated binding free energies and experimental ones all
      proved PFV IN is a promising screening platform for HIV-1 IN inhibitors. Then,
      the molecular recognition mechanism of PFV IN by its substrate viral DNA and six
      naphthyridine derivatives (NRDs) inhibitors was investigated through molecular
      docking, molecular dynamics simulations and water-mediated interactions analyses.
      The functional partition of NRDs IN inhibitors could be divided into hydrophobic
      and hydrophilic ones, and the Mg2+ ions, water molecules and conserved DDE motif
      residues all interacted with the hydrophilic partition, while the bases in viral
      DNA and residues like Tyr212, Pro214 interacted with the hydrophobic one.
      Finally, the free energy landscape (FEL) and cluster analyses were performed to
      explore the molecular motion of PFV IN-DNA system. It is found that the
      association with NRDs inhibitors would obviously decrease the motion amplitude of
      PFV IN-DNA, which may be one of the most potential mechanisms of IN inhibitors.
      This work will provide a theoretical basis for the inhibitor design based on the
      structure of HIV-1 IN.

PMID- 29055189
TI  - A mannose-specific C-type lectin from Fenneropenaeus merguiensis exhibited
      antimicrobial activity to mediate shrimp innate immunity.
AB  - Being one type of pattern recognition receptors (PRRs), lectins exhibit a crucial
      role in the defense mechanism of invertebrates which are deficient in an adaptive
      immune system. A new C-type lectin called FmLC3 was isolated from hepatopancreas
      of Fenneropenaeus merguiensis by cloning approaches, RT-PCR and 5' and 3' RACE
      (rapid amplification of cDNA ends). A full-length cDNA of FmLC3 contains 607 bp
      with one open reading frame of 480bp, encoding a 159-amino acids peptide. The
      predicted primary structure of FmLC3 is composed of a signal peptide, a
      carbohydrate recognition domain with an EPN motif and one Ca2+ binding site-2,
      including a double-loop region assisted by two conserved disulfide linkages.
      FmLC3 had a molecular mass of 17.96kDa and pI of 4.92. In normal or unchallenged
      shrimp, the mRNA expression of FmLC3 was detected only in hepatopancreas whilst
      its native proteins were found in hemolymph, heart, stomach and intestine but not
      in the expressed tissue, indicating that after being synthesized in
      hepatopancreas, FmLC3 would be secreted to other tissues. The significant up
      regulation of FmLC3 was manifested in shrimp challenged with Vibrio harveyi or
      white spot syndrome virus. After knockdown with gene-specific double-stranded RNA
      and following by co-pathogenic inoculation, the FmLC3 expression was severely
      suppressed with coherence of increasing in cumulative mortality and reduction of
      the median lethal time. Recombinant FmLC3 (rFmLC3) had agglutinating activity
      towards diverse bacterial strains in a Ca2+-dependent manner. Its activity was
      inhibited by lipopolysaccharide and mannose, implying that FmLC3 was mannose
      binding C-type lectin. Moreover, rFmLC3 could bind directly to various microbial
      strains with Ca2+-requirement. Otherwise, rFmLC3 exhibited the antimicrobial
      activity by inhibiting effectively the microbial growth in vitro. All these
      results signified that FmLC3 might act as PRR to recognize with a broad
      specificity for diverse pathogens, and contribute in shrimp immune response via
      the agglutination, binding and antimicrobial activity.

PMID- 29055190
TI  - Pinocembrin attenuates allergic airway inflammation via inhibition of NF-kappaB
      pathway in mice.
AB  - Pinocembrin, one of the primary flavonoids in propolis, possesses many biological
      activities, including anti-inflammation, anti-oxidation and immunoregulation.
      This study aimed to evaluate whether pinocembrin could attenuate ovalbumin (OVA)
      induced allergic airway inflammation in mice and to explore the possible
      mechanism. BALB/c mice sensitized and challenged with OVA were administered
      intraperitoneally with pinocembrin. Airway inflammation and airway
      hyperresponsiveness were examined. T-helper type (Th) 2 cytokines in
      bronchoalveolar lavage fluid (BALF) and OVA-specific immunoglobulin E (IgE) in
      serum were determined. The activation of nuclear factor kappa B (NF-kappaB) p65
      were also measured. Our results showed that pinocembrin resulted in significant
      inhibition of pathophysiological signs of allergic asthma, including increased
      pulmonary eosinophilia infiltration, mucus hypersecretion and airway
      hyperresponsiveness (AHR). Treatment with pinocembrin significantly reduced Th2
      cytokines interleukin (IL)-4, IL-5 and IL-13 in BALF, and OVA-specific IgE in
      serum. Moreover, pinocembrin treatment suppressed phosphorylation of inhibitor
      kappaBalpha (IkappaBalpha) and NF-kappaB subunit p65 activation in lung tissue of
      OVA-sensitized mice. These data suggest that pinocembrin may inhibit allergic
      airway inflammation, and providing potential benefits in the treatment of
      inflammatory disease.

PMID- 29055191
TI  - Design, isolation and evaluation of the binding efficiency of a DNA aptamer
      against interleukin 2 receptor alpha, in vitro.
AB  - High levels of CD25, as part of the IL-2 receptor, are expressed on the surface
      of the activated T lymphocytes and regulatory T cells, indicating that the
      soluble CD25 (sCD25) could be a clinically valuable tool for treating several
      diseases. Moreover, progress has been achieved in targeting the IL-2 receptor to
      treat autoimmune diseases, organ transplantation and certain hematological
      malignancies. In the current study, generation of an ssDNA aptamer (Apt51)
      against CD25 is reported. Apt51 bound to CD25 with high affinity (Kd=13.4nM) and
      specificity. Furthermore, Apt51 was truncated to two shortened variants that
      almost retained their high affinity for the CD25 protein. Moreover, Apt51 showed
      good affinity and selectivity for the recognition of CD25 on the cell surface.
      Importantly, the study showed that Apt51 interfered with the binding of CD25 to
      its ligand (IL 2) and consequently decreased the IL-2-induced Akt activation.

PMID- 29055192
TI  - Electrochemical immunosensor with nanocellulose-Au composite assisted multiple
      signal amplification for detection of avian leukosis virus subgroup J.
AB  - A sensitive sandwich-type electrochemical immunosensor was developed for the
      detection of avian leukosis virus subgroup J (ALV-J), which benefitted from
      multiple signal amplification involving graphene-perylene-3,4,9,10
      tetracarboxylic acid nanocomposites (GR-PTCA), nanocellulose-Au NP composites (NC
      Au) and the alkaline phosphatase (ALP) catalytic reaction. GR-PTCA nanocomposites
      on glassy carbon electrodes served as the immunosensor platform. Due to their
      excellent electrical conductivity and abundant polycarboxylic sites, the GR-PTCA
      nanocomposites allowed fast electron transfer and good immobilization of primary
      antibodies, thereby affording a strong immunosensor signal in the presence of ALV
      J. The detected signal could be further amplified by the introduction of NC-Au
      composites as a carrier of secondary antibodies (Ab2) and by harnessing the
      catalytic properties of Au and ALP. Under optimized testing conditions, the
      electrochemical immunosensor displayed excellent analytical performance for the
      detection of ALV-J, showing a linear current response from 102.08 to 104.0
      TCID50/mL (TCID50: 50% tissue culture infective dose) with a low detection limit
      of 101.98 TCID50/mL (S/N = 3). In addition to high sensitivity, the immunosensor
      showed very good selectivity, reproducibility and operational stability,
      demonstrating potential application for the quantitative detection of ALV-J in
      clinical diagnosis.

PMID- 29055193
TI  - Specific bioanalytical optical and photoelectrochemical assays for detection of
      methanol in alcoholic beverages.
AB  - Methanol is a poison which is frequently discovered in alcoholic beverages.
      Innovative methods to detect methanol in alcoholic beverages are being constantly
      developed. We report for the first time a new strategy for the detection of
      methanol using fluorescence spectroscopy and photoelectrochemical (PEC) analysis.
      The analytical system is based on the oxidation of cysteine (CSH) with hydrogen
      peroxide (H2O2) enzymatically generated by alcohol oxidase (AOx). H2O2 oxidizes
      capping agent CSH, modulating the growth of CSH-stabilized cadmium sulphide
      quantum dots (CdS QDs). Disposable screen-printed carbon electrodes (SPCEs)
      modified with a conductive osmium polymer (Os-PVP) complex were employed to
      quantify resulting CdS QDs. This polymer facilitates the "wiring" of in situ
      enzymatically generated CdS QDs, which photocatalyze oxidation of 1-thioglycerol
      (TG), generating photocurrent as the readout signal. Likewise, we proved that our
      systems did not suffer from interference by ethanol. The PEC assays showed better
      sensitivity than conventional methods, covering a wide range of potential
      applications for methanol quantification.

PMID- 29055194
TI  - A graphene quantum dots based electrochemiluminescence immunosensor for
      carcinoembryonic antigen detection using poly(5-formylindole)/reduced graphene
      oxide nanocomposite.
AB  - A novel electrochemiluminescence (ECL) immunosensor for ultrasensitive detection
      of carcinoembryonic antigen (CEA) was developed using signal amplification
      strategy based on poly(5-formylindole)/reduced graphene oxide nanocomposite
      (P5FIn/erGO) and Au nanoparticle (AuNP) decorated graphene quantum dots (GQDs)
      (GQDs@AuNP). As an effective matrix for immobilization of primary antibody (Ab1),
      P5FIn/erGO nanocomposite facilitated the ion transport during the redox reactions
      and provided larger surface areas for the immobilization of Ab1. GQDs@AuNP was
      used as labels to conjugate with secondary antibody (Ab2), which improved
      electron transfer capability with stable ECL intensity. The multiple
      amplification of P5FIn/erGO and GQDs@AuNP made the ECL immunosensor have a broad
      linear range from 0.1pgmL-1 to 10ngmL-1 and a low detection limit with 3.78fgmL
      1. In addition, this ECL immunosensor performed with admirable stability and good
      selectivity and reproducibility as well. When this immunosensor was used for the
      analysis of CEA in human serum, good recoveries were obtained. Thus, there will
      be a promising future in the early diagnosis of cancer to detect CEA.

PMID- 29055195
TI  - Antifouling aptasensor for the detection of adenosine triphosphate in biological
      media based on mixed self-assembled aptamer and zwitterionic peptide.
AB  - Direct detection of targets in complex biological media with conventional
      biosensors is an enormous challenge due to the nonspecific adsorption and severe
      biofouling. In this work, a facile strategy for sensitive and low fouling
      detection of adenosine triphosphate (ATP) is developed through the construction
      of a mixed self-assembled biosensing interface, which was composed of
      zwitterionic peptide (antifouling material) and ATP aptamer (bio-recognition
      element). The peptide and aptamer (both containing thiol groups) were
      simultaneously self-assembled onto gold electrode surface electrodeposited with
      gold nanoparticles. The developed aptasensor possessed high selectivity and
      sensitivity for ATP, and it showed a wide linear response range towards ATP from
      0.1pM to 5nM. Owing to the presence of peptide with excellent antifouling
      property in the biosensing interface, the aptasensor can detect ATP in complex
      biological media with remarkably reduced biofouling or nonspecific adsorption
      effect. Moreover, it can directly detect ATP in 1% human whole blood without
      suffering from any significant interference, indicating its great potential for
      practical assaying of ATP in biological samples.

PMID- 29055196
TI  - Urinary p-cresol diagnosis using nanocomposite of ZnO/MoS2 and molecular
      imprinted polymer on optical fiber based lossy mode resonance sensor.
AB  - A lossy mode resonance (LMR) based sensor for urinary p-cresol testing on optical
      fiber substrate is developed. The sensor probe fabrication includes dip coating
      of nanocomposite layer of zinc oxide and molybdenum sulphide (ZnO/MoS2) over
      unclad core of optical fiber as the transducer layer followed by the layer of
      molecular imprinted polymer (MIP) as the recognition medium. The addition of
      molybdenum sulphide in the transducer layer increases the absorption of light in
      the medium which enhances the LMR properties of zinc oxide thereby increasing the
      conductivity and hence the sensitivity of the sensor. The sensor probe is
      characterized for p-cresol concentration range from 0uM (reference sample) to
      1000uM in artificially prepared urine. Optimizations of various probe fabrication
      parameters are carried to bring out the sensor's optimal performance with a
      sensitivity of 11.86nm/uM and 28nM as the limit of detection (LOD). A two-order
      improvement in LOD is obtained as compared to the recently reported p-cresol
      sensor. The proposed sensor possesses a response time of 15s which is 8 times
      better than that reported in the literature utilizing electrochemical method. Its
      response time is also better than the p-cresol sensor currently available in the
      market for the medical field. Thus, with a fast response, significant stability
      and repeatability, the proposed sensor holds practical implementation
      possibilities in the medical field. Further, the realization of sensor probe over
      optical fiber substrate adds remote sensing and online monitoring feasibilities.

PMID- 29055197
TI  - Electrochemical inactivation of Cylindrospermopsis raciborskii and removal of the
      cyanotoxin cylindrospermopsin.
AB  - Much attention has been paid to ways of removing toxic cyanobacteria and
      cyanotoxins from water prior to its use due to public health concerns. The
      efficacy of treating the toxic filamentous cyanobacterium Cylindrospermopsis
      raciborskii (C. raciborskii) by electrolysis with a boron-doped diamond (BDD) in
      Chloride-free solution was investigated. At optimum current, about 87 and 93%
      removal of cell density at 60 and 180min and about 72 and 90% of Chl a,
      respectively. Additionally, a physiological test (FV/Fm) indicated that cells
      were completely inactivated in 45min. Furthermore, initial total
      cylindrospermopsin concentration 1.83MUg/L was also degraded to below the
      detection limit (<0.05MUg/L) in 30min. Hydroxyl radical (OH) played the major
      role in cell inactivation, however, Na2SO4 also played a minor role in algae
      removal due to the formation of SO4- and subsequently S2O82- by BDD electrode.
      The results of this study suggest that BDD electrochemical treatment of algae in
      Chloride-free water is feasible.

PMID- 29055198
TI  - Dual-competitive lateral flow aptasensor for detection of aflatoxin B1 in food
      and feedstuffs.
AB  - A novel dual-competitive lateral flow aptasensor (LFA) benefited from aptamer and
      lateral flow strips was first designed by using aflatoxin B1 (AFB1) as the model
      target. In this LFA assay, the target AFB1 competed with AFB1-hapten at T line
      for binding to Cy5-labeled AFB1 aptamer and the complementary strand competed
      with the target AFB1 for binding to Cy5-labeled AFB1 aptamer at C line. The ratio
      of their fluorescent intensities at the T line and C line (ST/SC ratio) was
      employed in order to increase the sensitivity for target AFB1 detection. This
      technique has the limit of detection (LOD) of 0.1ng/mL for AFB1 within the linear
      range from 0.1ng/mL to 1000ng/mL. Subsequently, the LFA approach was validated
      using 11 kinds of food and feedstuff samples with a simple aqueous extraction
      protocol. The test results with different naturally contaminated feedstuffs
      indicated a good correlation between this LFA and a commercial ELISA kit. The
      assay can be completed within 20min and its sensitivity, specificity and
      reproducibility are highly satisfactory. This is the first LFA that has been
      rigorously validated, which will be greatly beneficial to development of
      commercial aptamer-based biosensors for food safety, environmental analysis,
      particularly in clinical diagnosis.

PMID- 29055199
TI  - The removal of mercury ion pollution by using Fe3O4-nanocellulose: Synthesis,
      characterizations and DFT studies.
AB  - In this study, we have attempted to extract cellulose from Cystoseria myricaas
      algae. Nanocellulose, Fe3O4 and Fe3O4-nanocellulose compounds are synthesized by
      acid hydrolysis and co-precipitation as well as sol-gel methods The synthesized
      compounds are characterized by x-ray diffraction, transmission electron
      microscopy, particle size distribution (PSD), scanning electron microscopy
      (SEM),energy dispersive x-ray spectroscopy, vibrating sample magnetometer and
      Fourier transform infrared spectroscopy. The Hg (II) uptake on Fe3O4
      nanocellulose is investigated by 14 isotherm models, 12 kinetic models,
      adsorption activation energy as well as thermodynamic of adsorption. The polymers
      of algae and the interactions between Hg (II) and cellulose are investigated by
      density functional theory (DFT) in various conditions. The results of both
      simulations show a good agreement with experimental data.

PMID- 29055200
TI  - Growth inhibition of rice (Oryza sativa L.) seedlings in Ga- and In-contaminated
      acidic soils is respectively caused by Al and Al+In toxicity.
AB  - Limited information exists on the effects of emerging contaminants gallium (Ga)
      and indium (In) on rice plant growth. This study investigated the effects on
      growth and uptake of Ga and In by rice plants grown in soils with different
      properties. Pot experiment was conducted and the rice seedlings were grown in two
      soils of different pH (Pc and Cf) spiked with various Ga and In concentrations.
      The results showed concentrations of Ga, In, and Al in soil pore water increased
      with Ga- or In-spiking in acidic Pc soils, significantly decreasing growth
      indices. According to the dose-response curve, we observed that the EC50 value
      for Ga and In treatments were 271 and 390mgkg-1 in Pc soils, respectively. The
      context of previous hydroponic studies suggests that growth inhibition of rice
      seedlings in Ga-spiked Pc soils is mainly due to Al toxicity resulting from
      enhanced Al release through competitive adsorption of Ga, rather than from Ga
      toxicity. In-spiked Pc soils, both In and Al toxicity resulted in growth
      inhibition, while no such effect was found in Cf soils due to the low
      availability of Ga, In and Al under neutral pH conditions.

PMID- 29055201
TI  - Markers of genotoxicity and oxidative stress in farmers exposed to pesticides.
AB  - The effects of chronic exposure to pesticides can lead to the development of
      several diseases, including different types of cancer, since the genotoxic and
      mutagenic capacity of these substances can be observed. The objective of this
      study is to investigate the relation between the occupational exposure to various
      pesticides and the presence of DNA damage and oxidative stress. Blood samples
      from 50 rural workers (41 men and 9 women) exposed to pesticides, 46 controls (20
      men and 26 women) from the same city (Antonio Carlos, Santa Catarina state,
      Brazil) and 29 controls (15 men and 14 women) from another city (Florianopolis,
      Santa Catarina state, Brazil), were evaluated using the comet assay and the
      cytokinesis-block micronucleus (CBMN) technique for genetic damage, and the test
      of thiobarbituric acid reactive substances (TBARS) and catalase (CAT) activity
      for the oxidative stress. Cholinesterase activities were also determined, but
      there was no statistical difference among exposed workers and controls.
      Significant differences were found in DNA damage among groups. The comet assay
      performed on peripheral blood lymphocytes of these individuals had a
      significantly higher DNA damage index in the exposed group comparing to controls
      (p < 0.0001). MNi (p < 0.001), NBUDs (p < 0.005) and NPBs (p < 0.0001) were also
      found to be significantly higher in the exposed group. The TBARS values were
      significantly higher comparing to the Florianopolis control group (p < 0.0001).
      Even though CAT values were higher than controls, there was no statistical
      difference. Thus, it is concluded that the exposed individuals, participants of
      this study, are more subject to suffer genetic damage and, consequently, more
      susceptible to diseases resulting from such damages.

PMID- 29055202
TI  - TiO2 nanoparticles in seawater: Aggregation and interactions with the green alga
      Dunaliella tertiolecta.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) have been widely employed in industrial
      applications, thus rising concern about their impact in the aquatic environment.
      In this study we investigated the chemical behaviour of TiO2 NPs in the culture
      medium and its effect on the green alga Dunaliella tertiolecta, in terms of
      growth inhibition, oxidative stress, ROS (Reactive Oxygen Species) accumulation
      and chlorophyll content. In addition, the influence of exopolymeric substances
      (EPS) excreted by the microalgae on the stability of NPs has been evaluated. The
      physicochemical characterization showed a high propensity of TiO2 NPs to form
      micrometric-sized aggregates within 30min, large enough to partially settle to
      the bottom of the test vessel. Indeed, an increasing amount of TiO2 particles
      settled out with time, but the presence of EPS seemed to mitigate this behaviour
      in the first 6h of exposure where the main effects in D. tertiolecta were
      observed. TiO2 NPs did not inhibit the 72-h growth rate of D. tertiolecta, nor
      affected the cellular chlorophyll concentration in the range 0.01-10mgL-1. The
      time-course of ROS production showed an initial transient increase of ROS in TiO2
      NP-exposed algae compared to the control, concomitant with an enhancement of
      catalase activity. Interestingly, intracellular ROS was a small fraction of total
      ROS, the highest amount being extracellular. The occurrence of cell-mediated
      chemical transformations of TiO2 NPs in the external medium, related to the
      presence of EPS, has been evaluated. Our results showed that carbohydrates were
      the major component of EPS, whereas proteins of medium molecular weight (20
      80kDa) were preferentially bound to TiO2 NPs, likely influencing their biological
      fate.

PMID- 29055203
TI  - Insight into the heterogeneous adsorption of humic acid fluorescent components on
      multi-walled carbon nanotubes by excitation-emission matrix and parallel factor
      analysis.
AB  - The heterogeneous adsorption behavior of commercial humic acid (HA) on pristine
      and functionalized multi-walled carbon nanotubes (MWCNTs) was investigated by
      fluorescence excitation-emission matrix and parallel factor (EEM- PARAFAC)
      analysis. The kinetics, isotherms, thermodynamics and mechanisms of adsorption of
      HA fluorescent components onto MWCNTs were the focus of the present study. Three
      humic-like fluorescent components were distinguished, including one carboxylic
      like fluorophore C1 (lambdaex/lambdaem= (250, 310) nm/428nm), and two phenolic
      like fluorophores, C2 (lambdaex/lambdaem= (300, 460) nm/552nm) and C3
      (lambdaex/lambdaem= (270, 375) nm/520nm). The Lagergren pseudo-second-order model
      can be used to describe the adsorption kinetics of the HA fluorescent components.
      In addition, both the Freundlich and Langmuir models can be suitably employed to
      describe the adsorption of the HA fluorescent components onto MWCNTs with
      significantly high correlation coefficients (R2> 0.94, P< 0.05). The
      dissimilarity in the adsorption affinity (Kd) and nonlinear adsorption degree
      from the HA fluorescent components to MWCNTs was clearly observed. The adsorption
      mechanism suggested that the pi-pi electron donor-acceptor (EDA) interaction
      played an important role in the interaction between HA fluorescent components and
      the three MWCNTs. Furthermore, the values of the thermodynamic parameters,
      including the Gibbs free energy change (DeltaG degrees ), enthalpy change (DeltaH
      degrees ) and entropy change (DeltaS degrees ), showed that the adsorption of the
      HA fluorescent components on MWCNTs was spontaneous and exothermic.

PMID- 29055204
TI  - Influence of Bizerte city wastewater treatment plant (WWTP) on abundance and
      antibioresistance of culturable heterotrophic and fecal indicator bacteria of
      Bizerte Lagoon (Tunisia).
AB  - The waste water treatment plant (WWTP) of the city of Bizerte concentrates
      different types of chemical and biological pollutants in the Bizerte lagoon
      (Tunisia). Considering four upstream and downstream WWTP discharge stations,
      seventy nine, culturable bacterial strains were isolated and identified from
      water and sediment as fecal coliforms, fecal streptococci, pathogenic
      staphylococci and non-enterobacteriacea. Fecal coliforms were most abundant (2.5
      105 bacteria/mg) in sediment of WWTP discharge. Leuconostoc spp (23.1%) and
      Chryseomonasluteola (23.1%) were the most prevalent culturable fecal indicator
      bacteria (FIB) isolated at the upstream discharge stations. However,
      Staphylococcus xylosus (13.9%) was the most prevalent culturable FIB isolated at
      the WWTP discharge stations. Moreover, high antibioticresistance phenotypes were
      present in all sampling stations, but especially in WWTP discharge station in
      both water and sediment. Resistance levels in water and sediment, respectively
      were amoxicillin (58.8%; 34.8%), penicillin (50%; 31.6%), oxacillin (60%; 33.3%),
      cefotaxim (55.2%; 39.1%), ceftazidim (66.7%; 50%), gentamycin (42.9%; 38.9%),
      tobramycin (50%; 25%), vancomycin (33.3; 71.4%), amikacin (66.7%; 0%) and
      ciprofloxacin (100%; 100%). Interestingly, beta-lactam antibiotic resistant FIB
      were mostly isolated from water as well as from sediments of upstream and WWTP
      discharge station. Canonical correspondence analysis CCA correlating antibiotic
      resistance profile with the abiotic data showed that, in water column, culturable
      bacterial strains isolated in upstream WWTP discharge stations were interestingly
      correlated with the resistance to amikacin, oxacillin, cefotaxim, ciprofloxacin
      and gentamycin, however, in sediment, they were correlated with the resistance to
      amoxicillin, oxacillin, cefotaxim and vancomycin. Serious beta-lactams and
      aminoglycosides acquired resistance appeared mainly in fecal streptococci and
      pathogen staphylococci groups.

PMID- 29055205
TI  - Development of QSAR models for predicting the binding affinity of endocrine
      disrupting chemicals to eight fish estrogen receptor.
AB  - Endocrine disrupting effect has become a central point of concern, and various
      biological mechanisms involve in the disruption of endocrine system. Recently, we
      have explored the mechanism of disrupting hormonal transport protein, through the
      binding affinity of sex hormone-binding globulin in different fish species. This
      study, serving as a companion article, focused on the mechanism of
      activating/inhibiting hormone receptor, by investigating the binding interaction
      of chemicals with the estrogen receptor (ER) of different fish species. We
      collected the relative binding affinity (RBA) of chemicals with 17beta-estradiol
      binding to the ER of eight fish species. With this parameter as the endpoints,
      quantitative structure-activity relationship (QSAR) models were established using
      DRAGON descriptors. Statistical results indicated that the developed models had
      satisfactory goodness of fit, robustness and predictive ability. The Euclidean
      distance and Williams plot verified that these models had wide application
      domains, which covered a large number of structurally diverse chemicals. Based on
      the screened descriptors, we proposed an appropriate mechanism interpretation for
      the binding potency. Additionally, even though the same chemical had different
      affinities for ER from different fish species, the affinity of ER exhibited a
      high correlation for fish species within the same Order (i.e., Salmoniformes,
      Cypriniformes, Perciformes), which consistent with that in our previous study.
      Hence, when performing the endocrine disrupting effect assessment, the species
      diversity should be taken into account, but maybe the fish species in the same
      Order can be grouped together.

PMID- 29055206
TI  - Simultaneous stabilization/solidification of Mn2+ and NH4+-N from electrolytic
      manganese residue using MgO and different phosphate resource.
AB  - This study examined simultaneous stabilization and solidification (S/S) of Mn2+
      and NH4+-N from electrolytic manganese residue (EMR) using MgO and different
      phosphate resource. The characteristics of EMR NH4+-N and Mn2+ S/S behavior, S/S
      mechanisms, leaching test and economic analysis, were investigated. The results
      show that the S/S efficiency of Mn2+ and NH4+-N could reach 91.58% and 99.98%,
      respectively, and the pH value is 8.75 when the molar ratio of Mg:P is 3:1 and
      the dose of PM (MgO and Na3PO4.12H2O) is 8wt%. In this process, Mn2+ could mainly
      be stabilized in the forms of Mn(H2PO4)2.2H2O, Mn3(PO4)2.3H2O, Mn(OH)2, and
      MnOOH, and NH4+-N in the form of NH4MgPO4.6H2O. Economic evaluation indicates
      that using PM process has a lower cost than HPM and HOM process for the S/S of
      Mn2+ and NH4+-N from EMR at the same stabilization agent dose. Leaching test
      values of all the measured metals are within the permitted level for the GB8978
      1996 test suggested when the dose of PM, HPM and HOM is 8wt%.

PMID- 29055207
TI  - Hormonal contraceptive use in smokers: Prevalence of use and associations with
      smoking motives.
AB  - INTRODUCTION: While endogenous sex hormones influence smoking-related outcomes,
      little is known about the role of hormonal contraceptives (HCs). This is despite
      dated estimates suggesting that HC use is prevalent among female smokers.
      Therefore, we sought to update estimates of the prevalence of HC use among female
      smokers and explore the association of HC use with various smoking motives (SMs).
      METHODS: This online cross-sectional survey recruited female smokers between the
      ages of 18-35. Survey questions assessed smoking behavior, SMs, use of HCs, and
      menstrual cycle regularity. RESULTS: Participants (n=734) were, on average (+/
      standard deviation), 20.7+/-2.7 years old and smoked 7.3+/-6.7 cigarettes/day.
      The majority of females reported a history of HC use (85%) and half reported
      current use (48%). Cyclical HC users (n=227) scored significantly lower on three
      SMs compared to naturally-cycling women in the follicular phase (n=62) and
      significantly higher on 15 SMs compared to naturally-cycling women in the luteal
      phase (n=29). Women on cyclical HCs differed from women on long-acting HCs
      (n=128) on two SMs. Further, the naturally-cycling women in the follicular phase
      scoring significantly higher on 15 SMs compared to those in the luteal phase.
      DISCUSSION: These observations indicate that HC use remains prevalent in female
      smokers and may influence SMs. Additional research should replicate these
      observations and explore the implications on smoking cessation outcomes.

PMID- 29055208
TI  - Measuring alcohol use across the transition to adulthood: Racial/ethnic, sexual
      identity, and educational differences.
AB  - BACKGROUND: Patterns of alcohol use change from adolescence to adulthood and may
      differ based on race/ethnicity, sexual identity, and education. If alcohol use
      measures do not operate consistently across groups and developmental periods,
      parameter estimates and conclusions may be biased. OBJECTIVES: To test the
      measurement invariance of a multi-item alcohol use measure across groups defined
      by race/ethnicity, sexual identity, and college education during the transition
      to adulthood. METHODS: Using three waves from the National Longitudinal Study of
      Adolescent to Adult Health, we tested configural, metric, and scalar invariance
      of a 3-item alcohol use measure for groups defined by race/ethnicity, sexual
      identity, and college education at three points during the transition to
      adulthood. We then assessed longitudinal measurement invariance to test the
      feasibility of modeling developmental changes in alcohol use within groups
      defined by these characteristics. RESULTS: Overall, findings confirm notable
      variability in the construct reliability of a multi-item alcohol use measure
      during the transition to adulthood. The alcohol use measure failed tests of
      metric and scalar invariance, increasingly across ages, both between- and within
      groups defined by race/ethnicity, sexual identity, and college education,
      particularly among females. CONCLUSIONS: Measurement testing is a critical step
      when utilizing multi-item measures of alcohol use. Studies that do not account
      for the effects of group or longitudinal measurement non-invariance may be
      statistically biased, such that recommendations for risk and prevention efforts
      could be misguided.

PMID- 29055209
TI  - Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia
      patients relapsing after allogeneic stem cell transplantation.
AB  - BACKGROUND: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD)
      positive acute myeloid leukaemia (AML) relapsing after allogeneic stem cell
      transplantation (allo-SCT) has a dismal prognosis with limited therapeutic
      options. FLT3-ITD kinase inhibition is a reasonable but palliative experimental
      treatment alternative in this situation. Information on long-term outcome is not
      available. METHODS: We performed a long-term follow-up analysis of a previously
      reported cohort of 29 FLT3-ITD-positive AML patients, which were treated in
      relapse after allo-SCT with sorafenib monotherapy. FINDINGS: With a median follow
      up of 7.5 years, 6 of 29 patients (21%) are still alive. Excluding one patient
      who received a second allo-SCT, five patients (17%) achieved sustained complete
      remissions with sorafenib. Four of these patients are in treatment-free remission
      for a median of 4.4 years. INTERPRETATION: Sorafenib may enable cure of a
      proportion of very poor risk FLT3-ITD-positive AML relapsing after allo-SCT.

PMID- 29055210
TI  - Enantio-selective molecular dynamics of (+/-)-o,p-DDT uptake and degradation in
      water-sediment system.
AB  - Enantio-selective molecular dynamics of (+/-)-o,p-DDT uptake and degradation in
      water-sediment system is described. Both uptake and degradation processes of (-)
      o,p-DDT were slightly higher than (+)-o,p-DDT enantiomer. The optimized
      parameters for uptake were 7.0MUgL-1 concentration of o,p-DDT, 60min contact
      time, 5.0pH, 6.0gL-1 amount of reverine sediment and 25 degrees C temperature.
      The maximum degradation of both (-)- and (+)-o,p-DDT was obtained with 16 days,
      0.4MUgL-1 concentration of o,p-DDT, pH 7 and 35 degrees C temperature. Both
      uptake and degraded process followed first order rate reaction. Thermodynamic
      parameters indicated exothermic nature of uptake and degradation processes. Both
      uptake and degradation were slightly higher for (-)-enantiomer in comparison to
      (+)-enantiomer of o,p-DDT. It was concluded that both uptake and degradation
      processes are responsible for the removal of o,p-DDT from nature but uptake plays
      a crucial role. The percentage degradations of (-)- and (+)-o,p-DDT were 30.1 and
      29.5, respectively. This study may be useful to manage o,p-DDT contamination of
      our earth's ecosystem.

PMID- 29055211
TI  - Bio-affinity mediated immobilization of lipase onto magnetic cellulose
      nanospheres for high yield biodiesel in one time addition of methanol.
AB  - To synthesis biodiesel from palm oil in one-time addition of methanol and solvent
      free medium using CBD fused with C-terminal of lipase from G. stearothermophilus
      (GSlip-CBD) was immobilized onto magnetic cellulose nanosphere (MCNS). The
      immobilized matrix traits were preconceived by FT-IR, TEM and XRD. Perceptible
      biodiesel yield 98 and 73% was synthesized by GSlip-CBD-MCNS in 4 h and GSlip
      MCNS in 6 h under the optimized conditions of oil:methanol ratio (1:3.5),
      temperature (55 and 50  degrees C) and enzyme loading (15 U). Intriguingly, the
      operational stability of GSlip-CBD-MCNS was an easily attainable owing to the
      magnetic properties and could be reused up to 8th and19th cycles with 94 and 45%
      of biodiesel yield respectively, compared to GSlip-MCNS. Thus GSlip-CBD-MCNS
      could be a potential biocatalyst for higher yield of biodiesel and reusability in
      one step addition of methanol.

PMID- 29055212
TI  - Catalytic liquefaction of municipal sewage sludge over transition metal catalysts
      in ethanol-water co-solvent.
AB  - Catalytic liquefaction of (Municipal sewage sludge) MSS over transition metal
      catalysts in ethanol-water co-solvent (EWCS) was investigated. The effect of
      operating parameters like temperature, holding time, and ethanol-water ratio was
      discussed. CuSO4 was selected as the most efficient catalyst. The highest
      biocrude yield (47.45%) and liquefaction conversion (97.74%) was both obtained at
      the same conditions following: a reaction temperature of 270 degrees C, a holding
      time of 30min, an ethanol-water ratio of 1:1, and with CuSO4 as the catalyst.
      Optimized operating conditions reduced Sulfur and Nitrogen content in biocrude by
      55.0% and 14.6%, respectively. The obtained biocrude samples were analyzed and
      characterized by thermogravimetric analysis (TGA) and gas chromatography-mass
      spectroscopy (GC-MS), which suggested that adding CuSO4 increased the light-oil
      like content in biocrude and more than 60% of compounds in biocrude were esters.
      This process demonstrates the effectiveness of catalytic liquefaction of MSS in
      EWCS over CuSO4 catalyst.

PMID- 29055213
TI  - Degradation of Orange G by Fenton-like reaction with Fe-impregnated biochar
      catalyst.
AB  - This study was conducted to evaluate the catalytic activity of Fe-impregnated
      sugarcane biochar (FSB) for removing azo dye Orange G (OG) from solution under
      various Fenton-like oxidation conditions. The optimum molar Fe concentration for
      impregnation to achieve maximum catalytic activity of FSB in Fenton-like reaction
      with acceptable effluent Fe release was 0.25 M (163.4 Fe mg/g in FSB). High
      removal efficiency of 99.7% was achieved within 2 h of reaction at optimum
      conditions of 0.075 g/L H2O2, 0.5 g/L FSB for 0.1 g/L OG at initial pH 5.5 under
      25  degrees C. For every 10  degrees C increase, the time for maximum OG
      degradation efficiency decreased by 0.5 h. The OG removal by FSB exhibited a slow
      induction reaction followed by fast OG decomposition. FSB can be used
      successively for at least 4 runs with >89.3% OG removal. The FSB was more
      economical, efficient, and recyclable than other conventional Fenton oxidation
      catalysts.

PMID- 29055214
TI  - Effect of magnetic powder on membrane fouling mitigation and microbial
      community/composition in membrane bioreactors (MBRs) for municipal wastewater
      treatment.
AB  - This study aims to investigate the usefulness of magnetic powder addition in
      membrane bioreactors (MBRs) for membrane fouling mitigation and its effect on
      microbial community and composition. The comparison between the two MBRs (one
      with magnetic powder (MAS-MBR) and one without magnetic powder (C-MBR)) was
      carried out to treat synthetic municipal wastewater. Results showed that
      bioflocculation and adsorption of magnetic powder contributed only minimally to
      membrane fouling mitigation while the slower fouling rate might be ascribed to
      magnetic bio-effect. The macromolecules (larger than 500 kDa and 300-500 kDa) of
      soluble microbial product from the MAS-MBR were reduced by 24.06% and 11.11%,
      respectively. High-throughput sequencing demonstrated the most abundant genera of
      biofilm sludge indicated lower abundance in bulk sludge from the MAS-MBR compared
      to the C-MBR. It is possible that less membrane fouling is connected to
      reductions in large molecules and pioneer bacteria from bulk sludge.

PMID- 29055215
TI  - An insight into the adsorption of diclofenac on different biochars: Mechanisms,
      surface chemistry, and thermodynamics.
AB  - Biochars were prepared from feedstocks pinewood and pig manure. Biochar
      microparticles obtained through grinding were evaluated for the removal of
      emerging contaminant diclofenac (DCF) and the underlying mechanism were
      thoroughly studied. Characterization of biochar was carried out using particle
      size analyzer, SEM, BET, FT-IR, XRD, XPS and zeta potential instrument. Pig
      manure biochar (BC-PM) exhibited excellent removal efficiency (99.6%) over pine
      wood biochar (BC-PW) at 500 ug L-1 of DCF (environmentally significant
      concentration). Intraparticle diffusion was found to be the major process
      facilitated the adsorption. BC-PW followed pseudo first-order kinetics whereas BC
      PM followed pseudo second-order kinetics. Pine wood biochar was largely affected
      by pH variations whereas for pig manure biochar, pH effects were minimal owing to
      its surface functional groups and DCF hydrophobicity. Thermodynamics, presence of
      co-existing ions, initial adsorbate concentration and particles size played
      substantial role in adsorption. Various isotherms models were also studied and
      results are presented.

PMID- 29055216
TI  - Thoracic manual therapy is not more effective than placebo thoracic manual
      therapy in patients with shoulder dysfunctions: A systematic review with meta
      analysis.
AB  - BACKGROUND: Manual treatments targeting different regions (shoulder, cervical
      spine, thoracic spine, ribs) have been studied to deal with patients complaining
      of shoulder pain. Thoracic manual treatments seem able to produce beneficial
      effects on this group of patients. However, it is not clear whether the patient
      improvement is a consequence of thoracic manual therapy or a placebo effect.
      OBJECTIVES: To compare the efficacy of thoracic manual therapy and placebo
      thoracic manual treatment for patients with shoulder dysfunction. METHODS:
      Electronic databases (MEDLINE, CENTRAL, PEDro, CINAHL, WoS, EMBASE, ERIC) were
      searched through November 2016. Randomized Controlled Trials assessing pain,
      mobility and function were selected. The Cochrane bias estimation tool was
      applied. Outcome results were either extracted or computed from raw data. Meta
      analysis was performed for outcomes with low heterogeneity. RESULTS: Four studies
      were included in the review. The methodology of the included studies was
      generally good except for one study that was rated as high risk of bias. Meta
      analysis showed no significant effect for "pain at present" (SMD -0.02; 95% CI: 
      0.35, 0.32) and "pain during movement" (SMD -0.12; 95% CI: -0.45, 0.21).
      CONCLUSION: There is very low to low quality of evidence that a single session of
      thoracic manual therapy is not more effective than a single session of placebo
      thoracic manual therapy in patients with shoulder dysfunction at immediate post
      treatment.

PMID- 29055217
TI  - Trends in and factors affecting the observed levels of urinary inorganic and
      total blood mercury among US children, adolescents, adults, and senior citizens
      over 2005-2012.
AB  - Data from National Health and Nutrition Examination Survey (NHANES) for 2005-2012
      were used to (i) study adjusted and unadjusted trends in the levels of urinary
      inorganic mercury (UIHG) and total blood mercury (TBHG) and (ii) factors that
      affect the observed levels of UIHG and TBHG among children aged 1-5 (CHLD15) and
      6-11 (CHLD611) years, adolescents aged 12-19 years (ADOL), adults aged 20-64
      years (ADLT), and senior citizens aged >=65 years (SNR). Decrease in adjusted
      levels of UIHG for each 2-year NHANES cycle for CHLD611 was 0.08114ng/L,
      0.08379ng/L for ADOLs, and 0.12ng/L for ADLTs. Decreases in adjusted levels (AGM)
      of TBHG for each 2-year NHANES cycle were: 0.0632ng/L for CHLD15, 0.10239ng/L for
      CHLD611, 0.06424ng/L for ADOLs, and 0.056088ng/L for ADLTs. Among CHLD15 (0.34
      vs. 0.39MUg/L, p<0.01) and CHLD611 (0.42 vs. 0.44MUg/L, p=0.04), males had lower
      AGMs for TBHG than females but among ADLTs (0.84 vs. 0.80MUg/L, p<0.01) and SNRs
      (0.82 vs. 0.71MUg/L, p<0.01) the reverse was true. For UIHG, for ADLTs (0.33 vs.
      0.45MUg/L, p<0.01) and SNRs (0.27 vs. 0.35MUg/L, p<0.01) males had lower AGMs
      than females. Irrespective of age, those who were in unclassified race/ethnic
      group had the highest AGMs when compared with non-Hispanic whites, non-Hispanic
      blacks, and Mexican Americans and the differences, more often than not, were
      statistically significant (p<0.01). Irrespective of age, fish and shellfish
      consumption during the last 30days was associated with higher AGMs for both UIHG
      and TBHG than when fish and shellfish were not consumed and the differences were
      always statistically significant (p<0.01). Nonsmoker ADLTs (0.86 vs. 0.78MUg/L,
      p<0.01) and SNRs (0.83 vs. 0.71MUg/L, p<0.01) were found to have higher adjusted
      levels of TBHG than smokers. It is hypothesized that constituents in tobacco
      smoke may accelerate excretion of mercury from the body.

PMID- 29055219
TI  - Manual rotation in cases of the intrapartal arrest of fetal head.

PMID- 29055218
TI  - CYP2C9 and VKORC1 in therapeutic dosing and safety of acenocoumarol treatment:
      implication for clinical practice in Hungary.
AB  - The purpose of this work was to investigate the contribution of CYP2C9 and VKORC1
      to acenocoumarol (AC) dose variability, bleeding events in Hungary. The study
      recruited 117 patients on long-term AC therapy (INR 2-3), and 510 healthy
      individuals to model the findings. Patients were genotyped for alleles proved to
      affect lower AC overdose CYP2C9*2, CYP2C9*3, VKORC1*2. Additionally, we tested
      VKORC1*3, VKORC1*4 to examine their effect in patients with higher AC
      requirements. Most impact on dose reduction is accountable for CYP2C9*2/*3 (59%)
      and for VKORC1*2/*2 (45.5%), and on dose increase for newly evaluated VKORC1*3/*4
      (22.5%) diplotypes. VKORC1*3 and *4 alleles seem to balance the dose-reducing
      effect of VKORC1*2 allele. Being a carrier of combination of VKORC1*2 and
      CYP2C9*2,*3 polymorphisms, rather than of one of these SNPs, is associated with
      higher risk of over-anticoagulation (up to 34.3%) in long-term AC treatment. The
      pharmacogenetic dosing algorithm involving VKORC1, CYP2C9 diplotypes and age
      explains 30.4% of AC dosing variability (p<6.10*10-9). Correlation between the
      studied diplotypes and bleeding events could not be revealed.

PMID- 29055220
TI  - Laparoscopic fenestration of a large peritoneal inclusion cyst: Description of a
      new surgical technique.

PMID- 29055221
TI  - Cage with anterior plating is advantageous over the stand-alone cage for
      segmental lordosis in the treatment of two-level cervical degenerative
      spondylopathy: A retrospective study.
AB  - OBJECTIVES: To compare retrospectively the clinical and radiological outcomes in
      cervical spinal alignment after two consecutive levels PEEK cage-assisted ACDF
      when performed with or without plate fixation PATIENTS AND METHODS: Seventy-eight
      patients underwent two consecutive levels PEEK cage-assisted ACDF without plating
      (56 patients) or supplemented with plating (22 patients). The average clinical
      follow-up was 31.40+/-12.98months. The authors compared clinical parameters (Neck
      disability index and Robinson criteria), perioperative parameters (hospital
      stays, complications), and radiological parameters (global lordotic curvature,
      segmental lordosis, segmental height). RESULTS: Demographic features,
      neurological presentation, preoperative sagittal alignment, postoperative
      complications, length of hospitalization and clinical improvement were not
      different between groups. At 12-months radiological follow-up, the global
      lordotic curvature was similar in both groups (P=0.02). However, the use of
      anterior plate fixation versus stand-alone cage was associated with greater
      segmental lordosis (-7.68+/-4.82 degrees  versus -0.02+/-8.44 degrees , P<0.0001)
      and greater segmental height (39.51+/-3.50 versus 36.75+/-3.90, P=0.005).
      CONCLUSION: The clinical outcomes after two consecutive levels PEEK cage-assisted
      ACDF with and without plate fixation were similar, but the supplement of an
      anterior plate was advantageous for improving segmental alignment on long-term
      radiological follow-up.

PMID- 29055222
TI  - The cerebrospinal fluid values of advanced oxidation protein products and total
      thiol content in patients with amyotrophic lateral sclerosis.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is recognized as a progressive
      neurodegenerative disorder of unknown origin. Oxidative stress (OS) is considered
      as one of the most challenging hypothesis in the disease pathogenesis. The aim of
      this study was to contribute to the understanding of what extent there is
      involvement of OS in ALS. PATIENTS AND METHODS: We assessed Advanced Oxidation
      Protein Products (AOPP) and total thiol (-SH) groups in cerebrospinal fluid (CSF)
      of 24 ALS patients (13 of them presented with spinal form while 11 patients had
      bulbar form) and 20 controls (CG). RESULTS: The obtained AOPP levels in ALS
      patients were higher than those in CG (p <0.001), while -SH groups showed lower
      values compared to CG (p<0.001). The AOPP values were higher in ALS patients with
      bulbar compared with ALS patients with common spinal manifestation (p<0.001).
      There were no differences in -SH group's levels among these different clinical
      forms (p>0.05). The negative correlation between AOPP and the levels of -SH
      groups was confirmed (p <0.01). Significant mild correlations between tested
      parameters and functional rating scale as well as disease progression index were
      recorded for both of tested parameters in spinal form of ALS (p<0.01).
      CONCLUSION: The data presented here clearly support the fact that OS is involved
      in patophysiology of ALS, where oxidation of -SH groups represents an important
      aspect of protein oxidation. The CSF AOPP level and -SH groups may serve as
      potential useful biomarker for functional disorder and progression of the disease
      in the spinal form of ALS.

PMID- 29055223
TI  - Pituitary apoplexy - A single center retrospective study from the neurosurgical
      perspective and review of the literature.
AB  - OBJECTIVE: Thunderclap headache and visual disturbances are typical clinical
      features of pituitary apoplexy (PA). Because of the acute symptomatology, many
      patients are referred to a neurosurgical department without prior
      endocrinological assessment. It is the aim of the present study to analyze
      initial presenting symptoms, outcome and associated endocrine disturbances in a
      cohort of patients with pituitary apoplexy primarily seen by neurosurgeons.
      PATIENTS AND METHODS: Retrospective single-center study in a neurosurgical
      department. Patients' records were reviewed for clinical, neuropathological and
      endocrinological findings. The diagnosis of PA was based on clinical, imaging and
      histological findings. RESULTS: A total of 60 patients were studied. They were
      referred most often by neurologists (n=16), and family physicians (n=12). Only 2
      patients received an endocrinological work-up prior to admission. The most
      frequently documented presenting symptoms were headache (n=54), visual field
      defects (n=13), reduction of visual acuity (n=17) and/or diplopia (n=19). An
      endocrinological history had rarely been taken and hormone blood tests were
      oftentimes incomplete or not ordered. At 3-month follow-up 18/44 patients had
      complete anterior hypopituitarism. At 12 months, 21/60 patients were lost to
      endocrinological follow-up. CONCLUSIONS: The classic neurological symptoms of PA
      were well documented in our patient cohort, whereas endocrinological symptoms,
      especially those indicative of pituitary dysfunction were underreported.
      Neurologists and neurosurgeons need to be aware of the endocrinological sequelae
      of pituitary apoplexy in order to avoid potentially lethal complications.
      Patients should be counselled to adhere to long-term endocrinological and
      neurosurgical follow-up.

PMID- 29055224
TI  - Primary suction thrombectomy for acute ischemic stroke: A meta-analysis of the
      current literature.
AB  - OBJECTIVES: We conducted a meta-analysis to assess the angiographic and clinical
      outcomes for ischemic stroke patients treated with primary suction thrombectomy
      and to compare the procedural outcomes based on the treatment strategies (primary
      suction vs. stent retriever thrombectomy). PATIENTS AND METHODS: We conducted a
      systemic literature review through an online data base from January 2004 through
      December 2016. The primary outcomes were rate of successful recanalization on
      final angiogram and good outcome three months after stroke onset. We used a fixed
      effect model in cases with heterogeneity <50%. RESULTS: Fifteen articles were
      included. Primary suction thrombectomy achieved a successful recanalization rate
      of 85.2% (95% confidence interval [CI]: 79.9%-89.3%), a good clinical outcome
      rate of 52.7% (95% CI: 49.3%-56.2%) after the three-month follow-up, a mortality
      rate of 13.0% (95% CI: 8.9%-18.5%) and a symptomatic intracranial hemorrhage rate
      of 6.2% (95% CI: 4.8%-8.0%). The rates of recanalization (odds ratio [OR], 1.064;
      95% CI: 0.202-5.608; p=0.571) and good outcomes (OR, 0.920; 95% CI: 0.570-1.486;
      p=0.735) did not differ significantly between primary suction thrombectomy and
      stent retriever thrombectomy. CONCLUSION: Primary suction thrombectomy produced
      higher recanalization and good clinical outcome rates than did stent retriever
      thrombectomy. Larger-scale studies are necessary that consider factors such as
      occlusion site, stroke severity, and concomitant use of endovascular devices.

PMID- 29055225
TI  - Generation and characterization of a human iPSC line SANi005-A containing the
      gray platelet associated heterozygous mutation p.Q287* in GFI1B.
AB  - Peripheral blood mononuclear cells were isolated from an individual harboring a
      heterozygous c.859C->T p.Q287* mutation in GFI1B, causing an autosomal dominant
      bleeding disorder, platelet type, 17 (BDPLT17). PBMCs were differentiated to
      erythroblasts and reprogrammed by lentiviral delivery of a self-silencing hOKSM
      polycistronic vector. Pluripotency of iPSC line was confirmed by expression of
      associated markers and by in vitro spontaneous differentiation towards the 3 germ
      layers. Normal karyotype confirmed the genomic integrity of iPSCs and the
      presence of disease causing mutation was shown by Sanger sequencing. The
      generated iPSCs can be used to study BDPLT17 pathophysiology and basic functions
      of GFI1B.

PMID- 29055226
TI  - Generation of an induced pluripotent stem cell line, IBMS-iPSC-014-05, from a
      female autosomal dominant polycystic kidney disease patient carrying a common
      mutation of R803X in PKD2.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly
      inherited forms of polycystic kidney disease, and is characterized by the growth
      of numerous cysts in both kidneys. Here we generated an induced pluripotent stem
      cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 63-year
      old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the
      Sendai-virus delivery system. Downstream characterization of these iPSCs showed
      that they possessed normal karyotyping, were free of genomic integration,
      retained the disease-causing PKD2 mutation, expressed pluripotency markers and
      could differentiate into three germ layers.

PMID- 29055227
TI  - Generation and characterization of human iPSC lines SANi001-A and SANi002-A from
      mobilized peripheral blood derived megakaryoblasts.
AB  - Mobilized peripheral blood (MPB) CD34+ cells were differentiated to CD34+/CD41+
      megakaryoblasts. Cells were sorted to obtain a pure megakaryoblast population
      which was reprogrammed with a hOKSM self-silencing polycistronic lentiviral
      vector. Resulting iPSC showed normal karyotype and expression of pluripotency
      associated markers and in vitro spontaneous differentiation towards the 3 germ
      layers confirmed pluripotency of iPSC lines. Besides normal iPSC applications,
      these lines can be used as a control line for other megakaryoid origin iPSC and
      could be applied for epigenetic based research.

PMID- 29055228
TI  - Influence of ultrasound-assisted immersion freezing on the freezing rate and
      quality of porcine longissimus muscles.
AB  - The objective of this study was to evaluate the effect of ultrasound-assisted
      immersion freezing (UIF) on the freezing rate and quality of porcine longissimus
      muscles under different ultrasound powers. UIF with a certain level of ultrasound
      power significantly (P>0.05) accelerated the freezing rate. The phase transition
      times of samples treated with UIF at 180W (UIF-180) were the shortest. There were
      no significant differences (P>0.05) in a* (redness), b* (yellowness), pH values
      or cooking loss among UIF, IF, and control (fresh muscle) samples. Investigation
      of the microstructure of frozen muscles demonstrated that UIF-180 remarkably
      reduced the size of ice crystals and made their distribution more uniform. UIF
      180 samples showed a significant (P<0.05) reduction in thawing loss and T21 and
      T22 relaxation times compared with other treatments, which meant that UIF at
      certain powers could reduce the mobility and loss of immobilized and free water.
      The results showed that UIF at certain powers significantly increased the
      freezing rate of muscle samples and improved meat quality.

PMID- 29055229
TI  - Effect of long term chilled (up to 5weeks) then frozen (up to 12months) storage
      at two different sub-zero holding temperatures on beef: 2. Lipid oxidation and
      fatty acid profiles.
AB  - Lipid oxidation and fatty acid (FA) profiles were evaluated for beef M.
      longissimus lumborum (LL) stored under different chilled-then-frozen storage
      combinations (up to 5 and 52weeks, respectively) and two frozen holding
      temperatures (-12 degrees C and -18 degrees C). FA profile variation was
      observed, with increasing frozen storage periods resulting in unsaturated FA
      levels declining as saturated FA levels increased. Polyunsaturated and health
      claimable FA levels also tended to decline with increasing chilled storage
      period, albeit insignificant within the constraints of the experimental design.
      Peroxidase activity, TBARS and oxidation-reduction potential analyses reflected
      these FA changes. These, when compared against existing consumer thresholds,
      suggest a perceptible detraction from LL held under long-term frozen storage
      durations that are less evident earlier as dependent on the preceding chilled
      storage period. Negligible impact of frozen storage holding temperatures was
      observed on measured traits. These results suggest long-term chilled-then-frozen
      storage can influence beef lipid stability, healthy FA profile and therefore the
      healthiness of beef.

PMID- 29055230
TI  - Development and evaluation of novel biodegradable chitosan based metformin
      intrapocket dental film for the management of periodontitis and alveolar bone
      loss in a rat model.
AB  - OBJECTIVE: The aim of this study was to develop a chitosan-metformin based
      intrapocket dental film (CMIDF) for applications in the treatment of
      periodontitis and alveolar bone loss in an rat model of periodontitis. DESIGN:
      CMIDF inserts were fabricated by the solvent casting technique. The fabricated
      inserts were evaluated for physical characteristics such as folding endurance,
      surface pH, mucoadhesive strength, metformin content uniformity, and release. X
      ray diffraction analysis indicates no crystallinity of metformin in presence of
      chitosan which confirmed successful entrapment of metformin into the CMIDF.
      Fourier-transform infrared spectroscopy revealed stability of CMIDF and
      compatibility between metformin and chitosan. Periodontitis was induced by a
      combination of Porphyromonas gingivalis- lipopolysaccharide injections in
      combinations with ligatures around the mandibular first molar. We divided rats
      into 5 groups (8 rats/group): healthy, untreated periodontitis; periodontitis
      plus CMIDF-A (1.99+/-0.09mg metformin; total mass-4.01+/-0.05mg), periodontitis
      plus CMIDF-B (2.07+/-0.06mg metformin; total mass-7.56+/-0.09mg), and
      periodontitis plus chitosan film (7.61+/-0.08mg). After four weeks, mandibles
      were extracted to evaluate alveolar bone loss by micro-computerized tomography
      and histological techniques. RESULTS: Alveolar bone was intact in the healthy
      group. Local administration of CMIDF resulted in significant improvements in the
      alveolar bone properties when compared to the untreated periodontitis group. The
      study reported here demonstrates that novel CMIDF showed good antibacterial
      activity and effectively reduced alveolar bone destruction in a rat model of
      experimental periodontitis. CONCLUSIONS: Novel CMIDF showed good antibacterial
      activity and improved alveolar bone properties in a rat model.

PMID- 29055231
TI  - Correcting CFTR folding defects by small-molecule correctors to cure cystic
      fibrosis.
AB  - Pharmacological intervention to treat the lethal genetic disease cystic fibrosis
      has become reality, even for the severe, most common folding mutant F508del CFTR.
      CFTR defects range from absence of the protein, misfolding that leads to
      degradation rather than cell-surface localization (such as F508del), to
      functional chloride-channel defects on the cell surface. Corrector and
      potentiator drugs improve cell-surface location and channel activity,
      respectively, and combination therapy of two correctors and a potentiator have
      shown synergy. Several combinations are in the drug-development pipeline and
      although the primary defect is not repaired, rescue levels are reaching those
      resembling a cure for CF. Combination therapy with correctors may also improve
      functional CFTR mutants and benefit patients on potentiator therapy.

PMID- 29055232
TI  - Adverse events occurring on mental health units.
AB  - OBJECTIVE: While the study of suicide on mental health units has a long history,
      the study of patient safety more generally is relatively new. Our objective was
      to determine the type and relative frequency of adverse events occurring on
      Veterans Health Administration (VHA) mental health units; the primary root causes
      for these events; and make recommendations for abating or mitigating these
      events. METHODS: We searched our national database for any reported adverse event
      that occurred on an inpatient mental health unit between January 1, 2015 and
      December 31, 2016. We found 87 Root Cause Analysis (RCA) reports and 9780 safety
      reports. The safety reports were coded for type of event and the RCAs were
      further coded for underlying causes and severity. RESULTS: Of the 87 RCA reports,
      there were 31suicide attempts, 16 elopements, 10 assaults, 8 events involving
      hazardous items on the unit, 7 falls, 6 unexpected deaths, 3 overdoses and 6
      cases coded as "other". For the 9780 safety reports falls were the most common
      event, followed by medication events, verbal assaults, physical assaults, medical
      problems and hazardous items on the unit. CONCLUSIONS: As with medical units,
      patients on mental health units are at risk for many types of adverse events. The
      same focus on patient safety is just as important for our mental health patients
      as for our medical patients. Mental health unit staff should undertake a
      structured assessment of all risk on their units. This broad approach may be more
      successful than focusing on a particular event type.

PMID- 29055233
TI  - Do prolonged grief disorder symptoms predict post-traumatic stress disorder
      symptoms following bereavement? A cross-lagged analysis.
AB  - BACKGROUND: Bereavement can precipitate different forms of psychopathology,
      including prolonged grief disorder (PGD) and posttraumatic stress disorder (PTSD)
      symptoms. How these symptoms influence each other is unclear. The aim of this
      study was to examine the temporal relationship of symptoms of PGD and PTSD
      following bereavement. METHODS: We included 204 individuals, confronted with the
      loss of a loved one within the past year, who completed self-report measures of
      PGD and PTSD and again completed these measures one year later. We conducted a
      cross-lagged analysis to explore cross-lagged and autoregressive relationships.
      RESULTS: A significant cross-lagged relationship was found between PGD symptoms
      at time point 1 (T1) and PTSD symptoms at time point 2 (T2) (beta=0.270,
      p<0.001). Furthermore, PGD symptoms at T1 predicted PGD symptoms at T2 and PTSD
      symptoms at predicted PTSD symptoms at T2 (beta=0.617 and beta=0.458, ps<0.001,
      respectively). In addition, PGD and PTSD symptoms were significantly correlated
      on both time points. CONCLUSIONS: We found that PGD symptoms predict PTSD
      symptoms after a loss. Potentially, this could help to design new strategies and
      interventions for bereaved individuals. Additionally, PGD symptom levels
      predicted PGD symptom levels one year later, independently of the PTSD levels.
      This finding adds to the accumulating evidence that PGD is a distinct disorder.

PMID- 29055234
TI  - Evolving career choice narratives of new graduate nurses.
AB  - This article describes findings from one stage of a longitudinal study of the
      professional socialization experiences of Millennial nurses as they prepared for
      graduation and transition to practice. This study employed an interpretive
      narrative methodology guided by Polkinghorne's theory of narrative identity.
      Analysis of face-to-face interviews and journal entries by Millennial nursing
      students uncovered the formal professional socialization experiences over four
      years of nursing education. Participants include six Millennial nursing student
      participants (born after 1980) interviewed approximately one-month
      aftergraduation. These six participants are a voluntary subset of twelve who were
      interviewed prior to beginning their nursing studies, the analysis of which is
      captured in Price et al. (2013a) and Price et al. (2013b). Narrative analysis of
      the post-graduation interviews resulted in three main themes: 'Real Nursing:
      Making a Difference', 'The Good Nurse: Defined by Practice' and 'Creating Career
      Life Balance'. Graduate nurses strive to provide excellent nursing care as they
      transition into the workforce and identify a need for ongoing peer and
      professional supports to assist their ongoing professional socialization. Ongoing
      formal socialization and professional development is required to support the
      transition and retention of new nurse graduates in the workplace and the
      profession. Millenial generation nurses seek opportunities for career mapping,
      goal setting and formal mentorship by role models and peers to actualize their
      professional aspirations.

PMID- 29055235
TI  - A traditional American Indian death ritual: Developing nursing knowledge through
      aesthetic exposure.
AB  - The theoretical and practical application of Boykin and Schoenhofer's Nursing as
      Caring: A Model for Transforming Practice (2001) provided a framework for the
      exploration of an aesthetic project of quilting, which was undertaken in order to
      explain the death journey for a cherished mentor of American Indian nursing
      students. In particular, the nursing situation was used to guide the making of
      the quilt sampler. Aesthetics nested into the teaching-learning process became
      another way to help students solidify their professional self-identity as caring
      persons. This research has implications for the intentional development of
      studying quilting as an aesthetic way to express valuable lessons learned while
      caring for patients and telling stories. This idea of quilting opens up a line of
      enquiry into caring that can be expressed through a new and creative medium.

PMID- 29055236
TI  - The importance of academic literacy for undergraduate nursing students and its
      relationship to future professional clinical practice: A systematic review.
AB  - OBJECTIVES: This systematic review was designed to assess the importance of
      academic literacy for undergraduate nursing students and its relationship to
      future professional clinical practice. It aimed to explore the link between
      academic literacy and writing in an undergraduate nursing degree and the
      development of critical thinking skills for their future professional clinical
      practice. DESIGN: A systematic review of qualitative studies and expert opinion
      publications. DATA SOURCES: A systematic literature search was undertaken of the
      following databases: ERIC, PubMed, CINAHL, MEDLINE and Scopus. All papers
      reviewed were from 2000 to 2016 and were written in English. REVIEW METHODS: We
      identified 981 studies and expert opinion papers from the selected databases.
      After reviewing key words and abstracts for the inclusion and exclusion criteria,
      48 papers were selected for review. These were read and reread, with 22 papers,
      including one thesis, selected for quality appraisal. One paper was discarded due
      to the exclusion criteria. RESULTS: Three major themes were evident from this
      study. First, students need assistance to develop tertiary level academic
      literacy skills when they commence their undergraduate nursing degree. Second,
      that teaching practices need to be consistent in both designing assessments and
      in giving feedback to students, in order to assist improvement of academic
      literacy skills. And finally, academic literacy can facilitate critical thinking
      when students are assessed using discipline specific genres that relate to their
      future professional nursing practice. CONCLUSIONS: This review highlights the
      importance of critical thinking in clinical nursing practice and its strong
      relationship with academic writing skills. It has shown critical thinking is
      discipline specific and nursing students need to be taught discipline specific
      literacy genres in undergraduate nursing degrees. Nursing has a diverse
      educational and cultural mix of students, and educators should not assume
      academic literacy skills upon commencement of an undergraduate nursing programme.

PMID- 29055237
TI  - Mechanisms of action during a dissonance-based intervention through 14-month
      follow-up: The roles of body shame and body surveillance.
AB  - Objectification theory posits that internalization of societal perspectives about
      the female body leads to increased body surveillance, which can result in body
      related shame and subsequent eating disorder (ED) behaviors. Preliminary research
      indicates that these associations may be complex in nature. This study examined
      temporal relations among body surveillance, body shame, and eating disorder
      symptoms in the context of a dissonance-based body image intervention and through
      14-month follow-up. College women (N=285) completed assessments at baseline, post
      intervention, and at 8-week, 8-month, and 14-month follow-up. Cross-lag panel
      analyses revealed that changes in body surveillance significantly mediated the
      association between body shame and ED symptoms over time. Alternatively, body
      shame did not change over time and was not a significant mediator of associations
      between body surveillance and ED symptoms longitudinally. Results indicate that
      the ameliorative effects of dissonance-based interventions may be due to
      reductions in body surveillance, rather than decreased body shame.

PMID- 29055238
TI  - Patterns produced by dried droplets of protein binary mixtures suspended in
      water.
AB  - Patterns formed by the evaporation of a drop containing biological molecules have
      provided meaningful information about certain pathologies. In this context,
      several works propose the study of protein solutions as a model to understand the
      formation of deposits of biological fluids. Generally, dry droplets of proteins
      in a saline solution create complex aggregates. Here, we present an experimental
      study on the formation of patterns produced by the evaporation of droplet
      suspensions containing a protein binary mixture. We explore the structural aspect
      of such deposits by using optical and atomic force microscopy. We found that salt
      is unnecessary for the formation of complex structures such as crystal clusters,
      dendritic and undulated branches, and interlocked chains. Such structural
      features allow us to differentiate among protein binary mixtures. Finally, we
      discuss the potential use of this finding to reveal the presence of a protein
      suspensions, the folded and unfolded state of a protein, as well as their
      structural changes.

PMID- 29055239
TI  - Computed tomography detection of stapled interlobar fissure facilitates
      diagnosing postoperative lobar torsion: A case report.
AB  - INTRODUCTION: Atelectasis of the right middle lobe following right upper
      lobectomy may result from lobar torsion, bronchial kink, or impacted mucus plug.
      Although clinical consequence of lobar torsion could be serious, differentiating
      it from bronchial kink is occasionally challenging. PRESENTATION OF CASE: A 39
      year old man with non-small cell lung cancer of cT1aN0M0 stage IA underwent right
      upper lobectomy. On postoperative day 1, we identified middle lobe atelectasis on
      the chest X-ray and performed bronchoscopy, which showed an obstruction of the
      right middle lobe bronchus without mucoid impaction. We injected air using a
      bronchoscope to the middle lobe, which re-expanded it. However, on postoperative
      day 2, chest X-ray showed a slightly collapsed and opacified middle lobe.
      Although enhanced computed tomography showed a patent middle lobe pulmonary
      artery, we noticed that a staple placed in the horizontal fissure was in contact
      with the lower lobe, implying the possibility of lobar torsion. Rethoracotomy on
      postoperative day 2 revealed a 240 degrees  clockwise rotation of the congested
      middle lobe. Therefore, we performed simple detorsion. The patient was discharged
      10days after rethoracotomy without further adverse events. DISCUSSION: In our
      case, patency of the pulmonary artery and temporary improvement of the
      atelectasis using a bronchoscopic aeration maneuver could not rule out the
      possibility of lobar torsion. CONCLUSION: The position of the staple placed on
      the interlobar fissure should be evaluated using computed tomography in
      postoperative middle lobe atelectasis. If the aeration maneuver for middle lobe
      atelectasis using bronchoscope fails, rethoracotomy should be considered.

PMID- 29055240
TI  - Automatic processing of emotional facial expressions as a function of social
      anhedonia.
AB  - Anhedonia is an important feature of major depression and schizophrenia-spectrum
      disorders. Few neuroimaging studies have investigated neural alterations in high
      anhedonia, isolated from other psychopathological variables, by including only
      participants without clinical diagnoses. The present study examined healthy
      individuals scoring high (N = 18) vs. low (N = 19) in social anhedonia, who were
      carefully selected from a sample of N = 282 participants. To examine differences
      in automatic brain responses to social-affective stimuli between high vs. low
      social anhedonia participants, we used functional magnetic resonance imaging. To
      assess early, automatic stages of emotion processing, we administered a paradigm
      presenting brief (33ms), backward-masked happy, sad, and neutral facial
      expressions. Individuals high in social anhedonia demonstrated increased
      activation in the bilateral thalamus and left red nucleus in response to masked
      sad faces relative to individuals low in social anhedonia. No significant group
      differences in brain activation emerged in other regions known to be involved in
      emotion and reward processing, including the amygdala and nucleus accumbens. Our
      results suggest that high social anhedonia in otherwise healthy individuals is
      associated with exaggerated automatic reactivity in the thalamus, which is a
      brain structure that has been implicated in the mediation of attentional
      processes.

PMID- 29055241
TI  - Comparing parent and child reports of health-related quality of life and their
      relationship with leisure participation in children and adolescents with Cerebral
      Palsy.
AB  - The aim of this study was to examine the level of agreement between reports of
      health-related quality of life (HR-QoL) obtained from children and adolescents
      with cerebral palsy (CP) and their parents. We also examined the relationships
      between child and parent perception of the different domains of HR-QoL and
      participation dimensions. Sixty-nine children and adolescents with CP and their
      parents separately completed parallel forms of the KIDSCREEN questionnaire. The
      Spanish version of the Children's Assessment of Participation and Enjoyment
      (CAPE) was completed by the child/adolescent. Concordance between the children's
      and the parents' HR-QoL scores was analyzed via Pearson and intraclass
      correlations. Differences in means were tested using paired Student's t-tests.
      Chi-square tests were using to assess the incidence of personal variables in the
      agreement and disagreement of children-parents' responses. The relationships
      between HR-QoL and leisure participation was confirmed with Pearson's correlation
      coefficients. Correlations between child and parent HR-QoL scores were small in 7
      domains, medium in 2 and large in the Social Support & Peers domain. Children
      reported significantly better HR-QoL than their parents did. Participation was
      positively associated with specific domains of HR-QoL, but only weakly, and there
      were discrepancies between parent and child reports of HR-QoL. These findings
      provide interesting information about the importance of hearing the voices of
      children and adolescents with CP to promote HR-QoL and leisure participation.

PMID- 29055242
TI  - The efficacy of two activity-based interventions in adolescents with
      Developmental Coordination Disorder.
AB  - BACKGROUND: Adolescents with Developmental Coordination Disorder (DCD) usually
      experience psychomotor difficulties that affect their participation in everyday
      tasks and sports. Without effective intervention, adolescents show persistent
      motor deficits through adulthood. It is therefore critical to develop
      interventions to address the specific needs of this population. Studies
      evaluating the impact of motor interventions among adolescents with DCD are
      limited. AIM: The study evaluated the efficacy of two activity-based motor
      interventions in female adolescents with DCD. METHODS AND PROCEDURES: Forty-three
      female participants (Mean+/-SD: 14.3+/-1.1years) were identified as having DCD
      using the DSM-5 criteria. They were randomly assigned to either Task-oriented
      Functional Training (TFT) or Wii training. Both groups received 45min training
      per week for 14 weeks. Outcome measures included isometric muscular strength,
      motor proficiency, functional performance and participation in activities of
      daily living (ADL). OUTCOMES AND RESULTS: At the conclusion of the intervention,
      the two groups had significant improvement in muscular strength, motor
      proficiency, running and agility, predilection for physical activity and
      generalized self-efficacy. However, there was no difference in outcomes for the
      two interventions. CONCLUSIONS AND IMPLICATIONS: The findings highlight the
      potential benefits of activity-based motor interventions in reducing impairments,
      improving functional performance, and enhancing participation. These results
      support previous findings on the efficacy of task-oriented interventions and
      demonstrate the value of these approaches at all levels of functioning.

PMID- 29055243
TI  - Physiological vital sign ranges in newborns from 34 weeks gestation: A systematic
      review.
AB  - CONTEXT: The birth process and the moments thereafter are a crucial time for
      newborns as they adapt to extra uterine life. The adaptive process begins
      immediately and can take a number of days to complete. The process involves
      initiating and maintaining respirations, thermoregulation, and the change from
      foetal circulation to newborn circulation. The majority of newborns successfully
      adapt to extra uterine life, some experience difficulty. Early warning tools may
      assist clinicians identify early signs of failure to adapt and/or deterioration
      but these are dependent on 'Normal' vital sign reference ranges for triggering an
      escalation of care. Age-matched early warning tools may improve the sensitivity
      of tools. OBJECTIVE: To identify physiological vital sign reference ranges for
      newborns >=34 weeks gestation from two hours of age. DESIGN: Systematic Review.
      DATA SOURCES: Between August 2016 and January 2017, PubMed, CINAHL, Embase, The
      Cochrane Library databases, and conference abstracts were searched for primary
      studies published between 1946 and 2017. Reference lists of retrieved articles
      were reviewed for potential studies. REVIEW METHODS: Primary studies published in
      English that reported physiological vital sign reference ranges pertaining to
      well newborns born from 34 weeks gestation were selected. Two authors
      independently assessed eligibility of studies for inclusion. Titles and abstracts
      were matched with the inclusion criteria: studies investigating heart or
      respiratory rate, temperature, blood pressure and oxygen saturations in well
      newborns greater than 34 weeks gestational age. Assessment of quality and grading
      of level of evidence were assessed using National Health and Medical Research
      Council level of Evidence Hierarchy Table and the Quality Assessment Tool for
      Quantitative Studies. Any disagreements were resolved by consensus. Data were
      extracted by two reviewers. RESULTS: A total of 1497 primary studies were
      retrieved. Following screening and removal of duplicates and screening, 10
      primary studies investigating heart rate (n=1), respiratory rate (n=1),
      temperature (n=1), blood pressure (n=4) and oxygen saturations (n=3) were
      eligible for inclusion in this review. The populations studied included term
      (n=6) or both preterm and term newborns (n=4). No reference ranges for any vital
      sign measurements could be identified from the included literature. In addition,
      inconsistencies between vital sign parameters of newborns were identified between
      the studies. CONCLUSION: There is paucity of normal vital sign data in the late
      preterm >34 weeks and post term gestational age cohorts despite literature
      suggesting differences in physiological maturity between these cohorts.

PMID- 29055244
TI  - A pilot study comparing mechanical properties of tissue-engineered cartilages and
      various endogenous cartilages.
AB  - BACKGROUND: Mechanical properties of tissue-engineered cartilage and a variety of
      endogenous cartilage were measured. The main goal was to evaluate if the tissue
      engineered cartilage have similar mechanical characteristics to be replaced with
      rib cartilage in microtia reconstruction. Such study lays the foundation for
      future human clinical trials for microtia reconstruction. METHOD: Atomic force
      microscopy and compression testing were used to measure the viscoelasticity of
      tissue-engineered cartilage (stem cell seeded on Poly lactic co-glycolytic acid
      nanofibers and Pellet) and endogenous cartilage: conchal bowl, microtic ears,
      preauricular remnants, and rib. Atomic force microscopy, calculates biomaterial
      elasticity through force-deformation measurement and Hertz model. Compression
      testing determines the stress relaxation by measuring slope of stress reduction
      at 10% strain. FINDING: Tissue-engineered cartilage demonstrated elasticity
      (4.6kPa for pellet and 6.6kPa for PLGA) and stress relaxation properties (7.6 (SD
      1.1) kPa/s for pellet) most similar to those of native conchal bowl cartilage
      (31.8 (SD 18) kPa for the elasticity and 15.1 (SD 2.1) kPa/s for stress
      relaxation factor). Rib cartilage was most dissimilar from the mechanical
      characteristics of conchal cartilage and demonstrated the highest elastic modulus
      (361 (SD 372) kPa). Moreover, except preauricular cartilage samples, the level of
      elastic modulus increased with age. INTERPRETATION: The use of tissue-engineered
      cartilage developed via PLGA and Pellet methods, may be an appropriate substitute
      for rib cartilage in the reconstruction of microtic ears, however their
      mechanical characteristics still need to be improved and require further
      validation in animal studies.

PMID- 29055245
TI  - Biomechanical analysis of an interference screw and a novel twist lock screw
      design for bone graft fixation.
AB  - BACKGROUND: Malpositioning of an anterior cruciate ligament graft during
      reconstruction can occur during screw fixation. The purpose of this study is to
      compare the fixation biomechanics of a conventional interference screw with a
      novel Twist Lock Screw, a rectangular shaped locking screw that is designed to
      address limitations of graft positioning and tensioning. METHODS: Synthetic bone
      (10, 15, 20lb per cubic foot) were used simulating soft, moderate, and dense
      cancellous bone. Screw push-out and graft push-out tests were performed using
      conventional and twist lock screws. Maximum load and torque of insertion were
      measured. FINDINGS: Max load measured in screw push out with twist lock screw was
      64%, 60%, 57% of that measured with conventional screw in soft, moderate and
      dense material, respectively. Twist lock max load was 78% and 82% of that with
      conventional screw in soft and moderate densities. In the highest bone density,
      max loads were comparable in the two systems. Torque of insertion with twist lock
      was significantly lower than with conventional interference screw.
      INTERPRETATION: Based on geometric consideration, the twist lock screw is
      expected to have 35% the holding power of a cylindrical screw. Yet, results
      indicate that holding power was greater than theoretical consideration, possibly
      due to lower friction and lower preloaded force. During graft push out in the
      densest material, comparable max loads were achieved with both systems,
      suggesting that fixation of higher density bone, which is observed in young
      athletes that require reconstruction, can be achieved with the twist lock screw.

PMID- 29055246
TI  - Comparative analysis of multiple representative components in the herb pair
      Astragali Radix-Curcumae Rhizoma and its single herbs by UPLC-QQQ-MS.
AB  - The herb-pair, Astragali Radix (AR) and Curcumae Rhizoma (CR), often occurs in
      traditional herbal prescriptions used for cancer treatment in Asian areas. In
      clinical application, the AR-CR herb pair was often produced by different
      preparation methods or with raw materials from different sources, which raised a
      challenge for quality control of the herb-pair medicines. In this paper, ultra
      high performance liquid chromatography coupled to triple quadrupole tandem mass
      spectrometry method (UPLC-QQQ-MS) was applied for the first time to
      simultaneously determine 17 main bioactive components for quality control of AR
      CR herb pair. The chromatographic separation was studied on an ACQUITY UPLC BEH
      C18 column (100mm*2.1mm, 1.7MUm) with a mobile phase composed of 0.1% aqueous
      formic acid and acetonitrile using a gradient elution in 12min. The proposed
      method was optimized and validated by good linearity (r2>0.9970), limit of
      detection (0.33-10.78ng/mL), limit of quantification (0.81-2.54ng/mL), intra- and
      inter-day precisions (RSD<=3.64%, RSD<=5.68%), stability (RSD<=4.29%),
      repeatability (RSD<=5.98%), recovery (90.20-107.60%). The established method was
      successfully applied to comparative analysis of main bioactive components in AR
      CR herb pair and its single herbs, and quality evaluation of different batches of
      clinical dispensing granules. Compared to the single herb, the content of most
      liposoluble constituents such as curcumenol, curdione, isocurcumenol,
      furanodienone, curcumol, and germacrone were remarkable increased in their herb
      pair, suggesting mixed preparation produced synergistic effects on promoting the
      extraction of bioactive ingredients. This study is the first time to report the
      rapid and simultaneous analysis of 17 compounds in AR-CR herb pair by UPLC-QQQ
      MS, and provides a feasible method for holistic quality control of preparations
      containing AR-CR herb-pair.

PMID- 29055247
TI  - Optimization and validation of reverse phase HPLC method for qualitative and
      quantitative assessment of polyphenols in seaweed.
AB  - A simple reverse phase-high performance liquid chromatography (RP-HPLC) coupled
      to a diode array detector (DAD) and negative ion electrospray mass spectrometer
      (ESI-MS) method was developed for simultaneous identification and quantification
      of phenolic antioxidants in seaweed. The proposed method was validated in terms
      of linearity, limits of detection (LOD), limits of quantification (LOQ), recovery
      and intermediate precision. The calibration curves were linear with correlation
      coefficient ranging from 0.9909 to 0.9997 while the values of LOD (0.26
      0.82mg/L), LOQ (0.77-2.50mg/L), recovery (>=97.2%) and precision in terms of
      retention time (%RSD <=2.27) and peak area (% RSD <=5.11) were satisfactory.
      Brown seaweed Himanthalia elongata used in this study was extracted with 60%
      methanol and the crude extract was cleaned with SPE (Solid Phase Extraction)
      cartridge. HPLC-DAD-MS/MS analysis of the SPE fraction allowed the identification
      of 7 phenolic compounds comprising phlorotannins, hydroxybenzoic acid,
      hydroxycinnamic acid and flavonols subclasses of polyphenols. Quantitative
      analysis of these compounds revealed the presence of phloroglucinol (394.1+/
      4.33MUg/g), gallic acid (96.3+/-3.12MUg/g), chlorogenic acid (38.8+/-1.94MUg/g),
      caffeic acid (44.4+/-2.72MUg/g), ferulic acid (17.6+/-0.85MUg/g), myricetin
      (8.6+/-0.85MUg/g) and quercetin (4.2+/-0.15MUg/g), in the extract. The SPE
      fraction were tested for antioxidant capacity which were significantly (P <0.05)
      higher (EC50; 14.5+/-0.57mg/g) than the ascorbic acid (EC50; 35.8+/-0.59mg/g) and
      the crude extract (EC50; 46.3+/-0.48mg/g). The occurrence of all these phenolic
      antioxidant compounds in H. elongata extract suggested that the developed method
      is sensitive enough and reproducible and could be used for qualitative and
      quantitative assessment of polyphenols in seaweed.

PMID- 29055248
TI  - Simultaneous quantification of direct oral anticoagulants currently used in
      anticoagulation therapy.
AB  - Direct oral anticoagulants (DOACs) are among the most effective options to
      prevent serious thromboembolic events in patients with atrial fibrillation.
      Coagulation assays are used to assess DOAC activity, but lack the possibility to
      quantify drugs with concurrent pharmacodynamic effect. We developed a selective
      multi-drug assay to analyze apixaban, betrixaban, dabigatran, edoxaban, edoxaban
      M4, and rivaroxaban with ultra-performance liquid chromatography coupled to
      tandem mass spectrometry (UPLC/MS/MS) in plasma fulfilling all requirements of
      the FDA und EMA guidelines for bioanalytical method validation. Plasma samples
      were extracted using solid phase extraction in a 96-well micro volume format.
      Chromatographic separation was performed on a Waters BEH Phenyl 1.7MUm column
      coupled to tandem mass spectrometry. Extraction recoveries exceeded 80 %.
      Concentrations of 1-1000 ng/ml can be precisely quantified (correlation
      coefficient of >0.99) using 100 MUL plasma volume. Intra-day and inter-day
      accuracies ranged between 91.0 % and 116 %. Precisions at low and high
      concentrations were below 13.3 %. The method was applied within a clinical drug
      trial and eight short pharmacokinetic profiles of patients under DOAC therapy
      were analyzed. The assay allows for highly sensitive and selective simultaneous
      quantification of DOACs in patient plasma samples.

PMID- 29055249
TI  - Peptide nucleic acid as a selective recognition element for electrochemical
      determination of Hg2.
AB  - A novel electrochemical PNA-based biosensor for the determination of Hg2+ is
      described. The receptor layer, containing single strands of polythymine PNA
      (peptide nucleic acid), was formed at the surface of gold electrode. Due to the
      presence of thymine bases and peptide bonds, an interaction between Hg2+ ion and
      receptor layer occurs. The influence of chain modification - PNA vs. DNA - and
      type of redox marker - anionic AQMS-Na (sodium salt of anthraquinone-2-sulfonic
      acid) and FeII/III (potassium ferri/ferrocyanide) or cationic MB (methylene blue)
      and RuHex (hexaammineruthenium(III) chloride) - were studied. Proposed PNA-based
      biosensor with anionic AQMS-Na as a redox marker demonstrated significantly
      better analytical parameters, as compared to results obtained for other tested
      redox markers (for measurements at pH6.0). The linear response towards Hg2+ was
      in the range from 5 to 500nmol.L-1 with the detection limit of 4.5nmol.L-1. The
      developed sensor distinguishes itself with high selectivity towards Hg2+, even
      for solutions containing several interfering cations. Interactions between Hg2+
      and PNA receptor layer were studied using square wave voltammetry (SWV) and
      electrochemical impedance spectroscopy (EIS).

PMID- 29055250
TI  - Clinical characteristics of patients with diagnostic uncertainty of major
      depressive disorder.
AB  - BACKGROUND: Physicians do not always confidently diagnose psychiatric disorders.
      The present study was conducted to identify the clinical characteristics of
      patients in whom a definitive diagnosis of major depressive disorder (MDD) could
      not be established. METHODS: The participants were 199 consecutive outpatients
      with MDD, who were comprehensively diagnosed using the Mini International
      Neuropsychiatric Interview (MINI). The physician in charge of each patient
      quantified his/her sense of self-confidence in diagnosing the patient with MDD
      using the self-rating questionnaire in which the score ranged from 1 (not at all
      confident) to 5 (definitely MDD). Using multiple logistic regression, the
      demographic and clinical factors of the patients in the low diagnostic confidence
      group (score less than or equal to 3, n=79) were compared with those in the high
      diagnostic confidence group (more than 3, n=120). RESULTS: Comorbidity of anxiety
      disorders (odds ratio (OR), 4.7), absence of remission (OR, 3.6), and non
      melancholic features (OR, 3.5) were identified as the most discriminative
      variables associated with the low diagnostic confidence of MDD. CONCLUSION: The
      results show that physicians were unable to confidently diagnose MDD in 40% of
      the cases, and that comorbidity of anxiety disorders, absence of remission, and
      non-melancholic features independently predicted the diagnostic uncertainty of
      MDD.

PMID- 29055251
TI  - Consistency of selected craniometric landmark locations and the resulting
      variation in measurements.
AB  - Recently, forensic anthropology has undergone a major shift to quantitative
      methodologies, including the standardization of osteometric measurements. This
      study is an analysis of inter-observer error rates for eight "standardized"
      cranial measurements. Thirty participants, of varied experience, were asked to
      note the location of landmarks used in each measurement, and to record the
      resulting measurement. None of the tested measurements met the previously
      established 80% consensus rate necessary to be considered "standardized-in
      practice" [1]. The highest consensus rate was that of nasal breadth (67.9%),
      followed by that of the mastoid height (57.1%). This low precision yielded
      percent mean differences of 2-48% of the total measurement, with range
      differences of up to 42mm. These results indicate that the field should take
      steps to improve osteometric standardization, including re-examining all
      measurements currently listed in osteometric canon and re-issuing a comprehensive
      guide.

PMID- 29055252
TI  - The burden of central anticholinergic drugs increases pain and cognitive
      dysfunction. More knowledge about drug-interactions needed.

PMID- 29055253
TI  - Why can multimodal, multidisciplinary pain clinics not help all chronic pain
      patients?

PMID- 29055254
TI  - The effect of visual cues on performance in the ultimatum game in individuals
      with autism spectrum disorder.
AB  - The Ultimatum Game (UG) allows for the assessment of altruistic behavior as well
      as the perception of fairness. We examined the effects of visual social cues
      (gaze of others), factors associated with autism, and trust on UG performance in
      typical adults (TAs) and individuals with autism spectrum disorder (ASD). We
      hypothesized that individuals with ASD would be less affected by visual social
      cues than TAs. We recruited 30 TAs and 30 individuals with ASD. Participants
      completed 30 trials of the UG, during which the visual background was altered to
      include either stylized eyespots, flowers, or a neutral background. Reaction
      times and money distributed in each condition were recorded. Reaction times did
      not vary among background conditions in either group, although individuals with
      ASD responded more slowly overall. TAs distributed less money in the neutral
      background and flowers conditions than in the eyespots condition, while no
      significant differences in the amount of money distributed were observed among
      background conditions for individuals with ASD, who also distributed more money
      overall than TAs. Such findings may be due to decreased susceptibility to social
      cues among individuals with ASD.

PMID- 29055256
TI  - Radiotracer investigation and modeling of an activated sludge system in a pulp
      and paper industry.
AB  - A radiotracer investigation was carried out in an activated sludge process (ASP)
      system of an effluent treatment plant in a pulp and paper industry. The system
      consists of an aeration tank and a secondary clarifier connected in series. The
      primary objective of the investigation was to measure mean hydraulic retention
      times (MHRTs) of wastewater and investigate the hydraulic performance of the ASP.
      Residence time distributions (RTD) of the wastewater were measured in an aeration
      tank and a secondary clarifier of the system using Iodine-131 as a radiotracer.
      The measured RTD data was treated and MHRTs were estimated. No bypassing was
      found to exist in the aeration tank and the secondary clarifier. However, the
      dead volume in the aeration tank and the secondary clarifier was found and
      estimated to be 2.34% and 4.6%, respectively. The treated curves were further
      simulated using suitable hydraulically representative mathematical models and
      detailed flow patterns in the aeration tank and the secondary clarifier were
      deciphered.

PMID- 29055255
TI  - Determinant of receptor-preference switch in influenza hemagglutinin.
AB  - Influenza pandemic occurs when a new strain from other animal species overcomes
      the inter-species barriers and supports rapid human-to-human transmission. A
      critical prerequisite to this process is that hemagglutinin (HA) acquires a few
      key mutations to switch from avian receptors to human receptors. Previous studies
      suggest that H1 and H2/H3 HAs use different sets of mutations for the switch.
      This report shows that HA from the 1918 H1N1 pandemic virus (1918H1 HA) adopts
      the set of mutations used by H2/H3 HAs in receptor-preference switch when its 130
      loop is made similar to those of H2/H3 HAs. Thus, the 130-loop appears to be the
      key determinant for the different mutations employed by pandemic H1 or H2/H3 HA.
      The correlation of the mutational routes and the 130-loop as unraveled in this
      study opens the door for efficient investigation of mutations required by other
      HA subtypes for inter-human airborne transmission.

PMID- 29055257
TI  - Efficacy of adjunctive brexpiprazole on the core symptoms of major depressive
      disorder: A post hoc analysis of two pooled clinical studies.
AB  - BACKGROUND: Patients with major depressive disorder (MDD) who do not adequately
      respond to antidepressant treatment (ADT) may benefit from adjunctive atypical
      antipsychotics; however, certain agents target specific symptoms of depression
      and not the full syndrome. The aim of this analysis was to examine the effects of
      brexpiprazole, adjunct to ADT, on the core symptoms of MDD, defined using
      Montgomery-Asberg Depression Rating Scale (MADRS) items. METHODS: This was a post
      hoc analysis of data from two 6-week, randomized, double-blind studies of
      adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (n
      = 1056). Efficacy was assessed using the MADRS core symptom subscale (MADRS6) and
      individual items (apparent sadness, reported sadness, inner tension, lassitude,
      inability to feel, and pessimistic thoughts). RESULTS: At Week 6, adjunctive
      brexpiprazole showed a greater effect than adjunctive placebo on the MADRS6
      (within-group Cohen's d effect sizes: brexpiprazole, 1.05; placebo, 0.71; p <
      0.001 between groups) and on each of the six core symptoms (effect sizes:
      brexpiprazole, 0.64-0.94; placebo, 0.39-0.64; all p < 0.001). At Week 2,
      adjunctive brexpiprazole already showed a greater effect than adjunctive placebo
      on the MADRS6, and on five of the core symptoms (all p < 0.01). LIMITATIONS: This
      was a post hoc analysis of studies that were not designed for this purpose.
      Correction for multiple comparisons was not performed. CONCLUSIONS:
      Brexpiprazole, as adjunct to ADT, produced a statistically significant and
      clinically meaningful improvement on the core symptoms of MDD. Brexpiprazole is
      thought to exert its effects in MDD by treating the core symptoms of the disease.

PMID- 29055258
TI  - Cognitive functioning in first episode bipolar I disorder patients with and
      without history of psychosis.
AB  - BACKGROUND: Psychosis in bipolar I disorder (BDI) has been associated with
      increased cognitive dysfunction, which may relate to poorer functional outcomes.
      However, it is not known whether cognition differs between BDI patients with
      (BDP+) or without (BDP-) history of psychosis early in the disease course, or if
      it is impacted by the presence of mood congruent (MCP) versus incongruent (MIC)
      psychotic features. We compare cognition between these groups in BDI patients
      recently recovered from first episode of mania. METHODS: Attention, verbal
      learning/memory, processing speed and executive functioning were compared
      between: 1) all BDI patients (n = 73) and healthy controls (HC, n = 45), 2) BDP+
      (n = 60) and BDP- (n = 13) patients and 3) MCP (n = 27) and MIC (n = 33)
      patients. Post-hoc analyses compared all patient groups with HC. RESULTS: While
      BDI patients performed worse than HC in all domains, there were no significant
      differences between BDP+ and BDP-, or MCP and MIC, patients. However, BDP+ and
      MIC groups demonstrated different patterns of impairment compared to HC then did
      BDP- or MCP. Executive functioning and cognitive flexibility in particular
      appeared to be a deficit area in BDP+ patients. LIMITATIONS: This study may have
      been underpowered to detect differences in direct comparison between BDP+ and BDP
      patients. CONCLUSION: While replication in larger samples is required, these
      results suggest that subtle cognitive differences between BDP+ and BDP-, and
      between MIC and MCP, patients may be present shortly after disease onset. These
      patient subsets may therefore be of interest in examining early intensive
      strategies to preserve cognition.

PMID- 29055259
TI  - Functional impairment in adult bipolar disorder with ADHD.
AB  - BACKGROUND: It is well established that patients with either bipolar disorder
      (BD) or attention-deficit/hyperactivity disorder (ADHD) present functional
      impairment even when in remission. Nevertheless, research on functional
      impairment with adult patients with bipolar disorder comorbid to ADHD (BD+ADHD)
      is very scarce. The main objective of the current report was to evaluate the
      overall and specific domains of functioning, in patients with BD+ADHD compared to
      patients with pure bipolar disorder (pBD) and healthy controls (HCs). METHOD: 162
      subjects from 3 groups were compared: 63 pBD, 23 BD+ADHD and 76 HCs. All the
      patients with BD had been euthymic for at least 6 months and they were recruited
      at the Hospital Clinic of Barcelona. All the participants were assessed with the
      17-item Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale
      (YMRS) and the Functioning Assessment Short Test (FAST). Clinical, and
      sociodemographic data were also recorded. RESULTS: Clinical groups, pBD and
      BD+ADHD, showed lower overall functioning (p < 0.001) in each domain of the FAST
      scale compared to the HCs. Moreover, the Tukey post hoc test revealed that the
      BD+ADHD group showed a worse score than pBD in the cognitive domain of the FAST.
      However, after controlling for potential confounding variables, only the HDRS
      scores (p < 0.026) remained significant for the cognitive domain of the FAST.
      LIMITATIONS: The small sample size of the comorbid BD+ADHD group. CONCLUSIONS:
      Adult patients with BD+ADHD showed the worst scores in functioning compared with
      the HCs, but did not show more severe functional impairment than the pBD group
      except for the cognitive domain. Therefore our findings suggest that depressive
      symptoms in adults with BD+ADHD may negatively influence cognitive functioning.
      Further studies are needed to confirm our findings for the management of BD+ADHD.

PMID- 29055260
TI  - Swimming exercise reverses CUMS-induced changes in depression-like behaviors and
      hippocampal plasticity-related proteins.
AB  - BACKGROUND: Stress-induced failed resilience of brain plasticity can contribute
      to the onset and recurrence of depression. Chronic stress has been reported to
      open windows of epigenetic plasticity in hippocampus. However, how hippocampal
      plasticity underlies depression-like behaviors and how it adapts in response to
      stress has not been addressed. The present study aimed to investigate the
      signaling mechanisms of CUMS affecting hippocampal plasticity-related proteins
      expression and the regulation of swimming exercise in mice. METHODS: Male C57BL/6
      mice were subjected to chronic unpredictable mild stress (CUMS) for 7 weeks. From
      the 4th week, CUMS mice were trained in a moderate swimming program for a total
      of 4 weeks. A videocomputerized tracking system was used to record behaviors of
      animals for a 5-min session. Real-time PCR and Western Blotting were used to
      examine gene expression in mouse hippocampus. RESULTS: Our results demonstrated
      that CUMS induced depression-like behaviors, which were reversed by swimming
      exercise. Moreover, the behavioral changes induced by CUMS and exercise were
      correlated with hippocampal plasticity-related proteins expression of growth
      associated protein-43 (GAP-43) and synaptophysin (SYN). The molecular mechanisms
      regulating this plasticity may include SIRT1/mircoRNA, CREB/BDNF, and AKT/GSK
      3beta signaling pathways. LIMITATIONS: We did not establish a correlation between
      depression-like behaviors induced by chronic stress and epigenetic changes of
      hippocampal plasticity, either a causal molecular signaling underling this
      plasticity. CONCLUSIONS: Our findings have identified swimming exercise effects
      on CUMS-induced changes in depression-like behaviors and hippocampal plasticity
      related proteins, which provide a framework for developing new strategies to
      treat stress-induced depression.

PMID- 29055261
TI  - The NoSAS score: A new and simple screening tool for obstructive sleep apnea
      syndrome in depressive disorder.
AB  - BACKGROUND: Since the clinical presentation of obstructive sleep apnea syndrome
      (OSAS) shares common features with major depressive (MDE), the screening of OSAS
      is challenging in this population. The aim of this study was to assess the
      effectiveness of the NoSAS score in predicting the presence of OSAS among
      participants with current MDE and to compare it with the performance of existing
      screening tools. METHODS: A random sample of the population-based cohort CoLaus
      (Lausanne, Switzerland) underwent a psychiatric evaluation (PsyCoLaus) and a
      complete polysomnography at home (HypnoLaus). The effectiveness of the NoSAS
      score in detecting the risk of significant OSAS among current MDE participants
      was assessed and compared with STOP-BANG and Berlin scores. RESULTS: Among the
      1761 subjects (58,75 +/- 11y.o.; 47,8%men) who underwent polysomnography,
      significant OSAS was present in 24.0% with and 26.1% without current MDE. Using a
      threshold of >= 8 points, the NoSAS score identified OSAS in MDE participants
      with a sensitivity of 0.79, a specificity of 0.66, a negative predictive value of
      0.91, and a positive predictive value of 0.41. The area under the ROC curve was
      0.72 for NoSAS, 0.66 for STOP-BANG and 0.69 for the Berlin score (NS).
      LIMITATIONS: Only 44% of the PsyCoLaus participants had a polysomnography. The
      studied population was mainly of Caucasian ancestry and above 40 years of age.
      CONCLUSIONS: This is the first study assessing the performance of screening tools
      for OSAS in MDE. The NoSAS score is a simple and efficient screening tool for
      OSAS in this population, and may be a helpful instrument for clinicians.

PMID- 29055262
TI  - Emergency residential care settings: A model for service assessment and design.
AB  - There have been calls for uncovering the "black box" of residential care
      services, with a particular need for research focusing on emergency care settings
      for children and youth in danger. In fact, the strikingly scant empirical
      attention that these settings have received so far contrasts with the role that
      they often play as gateway into the child welfare system. To answer these calls,
      this work presents and tests a framework for assessing a service model in
      residential emergency care. It comprises seven studies which address a set of
      different focal areas (e.g., service logic model; care experiences), informants
      (e.g., case records; staff; children/youth), and service components (e.g., case
      assessment/evaluation; intervention; placement/referral). Drawing on this process
      consultation approach, the work proposes a set of key challenges for emergency
      residential care in terms of service improvement and development, and calls for
      further research targeting more care units and different types of residential
      care services. These findings offer a contribution to inform evidence-based
      practice and policy in service models of residential care.

PMID- 29055263
TI  - Sub-cortical brain morphometry and its relationship with cognition in rolandic
      epilepsy.
AB  - PURPOSE: Rolandic epilepsy (RE), also called benign epilepsy with centrotemporal
      spikes (BECTS) is the most common childhood epilepsy syndrome. RE is associated
      with cognitive difficulties, which can affect children's quality of life. The
      underlying causes of these cognitive impairments are unclear. The objective of
      this prospective study is to investigate sub-cortical morphological alterations
      in RE children with left, right, or bilateral hemispheric focus and its
      association with cognition. METHODS: Participants include 41 children with
      rolandic epilepsy and 38 healthy controls (age 8-14 years), recruited from CHU
      Sainte-Justine Montreal Children Hospital (N=40) and Basel's Children Hospital
      (N=39). Quantitative volumetric assessment of putamen and caudate structures was
      performed on T1-weighted MR scans along with the morphological analysis to test
      for differences between patients and controls. These analyses were performed
      considering the side of epilepsy focus in all participants. Correlations were
      investigated between the sub-cortical morphometry and cognitive indices such as
      intelligence quotient (IQ), verbal comprehension index (VCI), perceptual
      reasoning index (PRI), working memory index (WMI), and processing speed index
      (PSI). RESULTS: Children with bilateral BECTS showed statistically significant
      volume reduction in right caudate (p<.05), while no statistically significant
      putamen volumetric changes were detected in BECTS participants compared to normal
      controls. According to a spectral-based groupwise shape analysis, regional
      alterations were found in both putamen and caudate structures of children with
      BECTS. In particular, children with left BECTS showed significant outward local
      deformity in left putamen and individuals with bilateral BECTS showed inward
      local group differences in both right putamen and right caudate. The correlation
      assessment showed positive association between the volume of the left caudate and
      cognitive indices in the group containing all BECTS participants. Negative
      correlation was found between putamen sub-regional shape alterations and
      cognition in individuals with right BECTS and in all BECTS participants. Negative
      associations between caudate sub-regional morphologies and cognitive indices were
      detected in left cohort. SIGNIFICANCE: We have confirmed putamen and caudate
      shape alterations in children with BECTS. However, our results further suggest
      that variations in sub-cortical shape affect cognitive functions. Importantly, we
      have demonstrated that shape alterations and their relation with cognition depend
      on the side of epilepsy focus. Our results point to different syndromic entities
      in the BECTS population.

PMID- 29055264
TI  - Differences in immunomodulatory properties between venlafaxine and paroxetine in
      patients with major depressive disorder.
AB  - Inflammatory processes play a crucial role in the pathophysiology of depression,
      and identifying the specific cytokines targeted by different antidepressants is
      important for personalized treatment. The aims of this study were to examine
      whether venlafaxine and paroxetine cause different immunomodulatory effects when
      used to treat patients with major depression and to clarify the relationships
      between plasma cytokine levels and the therapeutic effectiveness of these drugs.
      A total of 91 Han Chinese patients with major depression completed the 8-week
      paroxetine or venlafaxine treatment and 90 healthy controls were recruited. A
      multiplex assay was used to measure cytokines levels in patients with major
      depression before and after an 8-week venlafaxine and paroxetine treatment.
      Cytokine levels were measured in healthy controls at the baseline. The 21-item
      Hamilton Depression Rating Scale was used to assess the changes in
      psychopathological symptoms from the baseline to the end point in each patient.
      Venlafaxine treatment caused greater decreases in the levels of interferon gamma
      (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 4 (IL-4), IL-5,
      IL-1beta, and IL-8 than did paroxetine. Paroxetine treatment increased the levels
      of proinflammatory cytokines IFN-gamma, TNF-alpha, and IL-6 and decreased Th2
      cytokine levels. After paroxetine treatment, IL-6 levels increased more in the
      non-remitter group than in the remitter group. In the remitter group, IL-4 and IL
      5 levels decreased to values seen in the healthy controls. After venlafaxine
      treatment in both the remitter and non-remitter groups, IL-1beta levels decreased
      to values seen in the healthy controls. Our results suggest that venlafaxine and
      paroxetine have different immunomodulatory properties and that venlafaxine has
      greater anti-inflammatory effects than paroxetine.

PMID- 29055265
TI  - Input of different kinds of soluble pectin to cation binding properties of roots
      cell walls.
AB  - It is widely believed that pectin are responsible for the vast majority of cation
      binding positions in the root cell walls. To estimate the role of particular
      kinds of pectin, we studied the cell wall material isolated from the roots of
      monocots (wheat and rye) and dicots (clover and lupine) before and after removal
      of different fractions of soluble pectin. Simultaneously PME activity and degree
      of pectin methylation were determined. From potentiometric titration curves
      cation exchange capacity, total surface charge and acidic strength of surface
      functional groups responsible for surface charging were determined. Monocots had
      smaller cation exchange capacity and lower pectin content than dicots. Removal of
      pectin induced up to 50% reduction in the cell walls surface charge. Pectin seem
      to have more acidic character than the other roots components that is seen from
      an increase in very weakly acidic groups fraction and significant decrease in the
      average dissociation constant of the cell walls material after pectin removal.
      Water soluble pectin and non-pectic soluble compounds had the dominant role in
      surface charging, while chelator and diluted alkali soluble pectin contributed to
      surface charge only at high pH's.

PMID- 29055266
TI  - Geographical inequalities in health in a time of austerity: Baseline findings
      from the Stockton-on-Tees cohort study.
AB  - Stockton-on-Tees has the highest geographical inequalities in health in England
      with the life expectancy at birth gap between the most and deprived
      neighbourhoods standing at over 17 years for men and 11 years for women. In this
      study, we provide the first detailed empirical examination of this geographical
      health divide by: estimating the gap in physical and general health (as measured
      by EQ. 5D, EQ. 5D-VAS and SF8PCS) between the most and least deprived areas;
      using a novel statistical technique to examining the causal role of compositional
      and contextual factors and their interaction; and doing so in a time of economic
      recession and austerity. Using a stratified random sampling technique, individual
      level survey data was combined with secondary data sources and analysed using
      multi-level models with 95% confidence intervals obtained from nonparametric
      bootstrapping. The main findings indicate that there is a significant gap in
      health between the two areas, and that compositional level material factors,
      contextual factors and their interaction appear to be the major explanations of
      this gap. Contrary to the dominant policy discourse in this area, individual
      behavioural and psychosocial factors did not make a significant contribution
      towards explaining health inequalities in the study area. The findings are
      discussed in relation to geographical theories of health inequalities and the
      context of austerity.

PMID- 29055267
TI  - Nature differences of fulvic acid fractions induced by extracted sequence as
      explanatory factors for binding characteristics of Cu2.
AB  - The isolation of fulvic acid (FA) fractions with relatively homogeneity is a key
      to reveal the binding mechanisms between FA and heavy metals. In this work, nine
      FA fractions were obtained using sequential alkali extraction procedure and
      nature differences of the extracted FA fractions were considered as explanatory
      factors for binding characteristics of Cu2+. The results indicate that the
      contents of carboxyl and phenolic groups decrease with increasing extractions
      along with an opposite trend for the content of nitrogen-containing groups. The
      fitted results of ligand binding and bi-Langmuir models indicate that the binding
      sites for Cu2+ were mainly provided by carboxyl and phenolic groups, which
      explained the higher sorption capacity and binding affinity of earlier extracted
      FAs due to its higher contents of carboxyl and phenolic groups. Furthermore, the
      systemic characterization of FA fractions before and after adsorption indicate
      the nitrogen-containing groups were gradually showing their contribution in
      binding Cu2+ with increasing extractions. This work is very helpful to insight
      the environmental effects of natural organic matter and the behavior of heavy
      metals in natural environment.

PMID- 29055268
TI  - Early age of e-cigarette use onset mediates the association between impulsivity
      and e-cigarette use frequency in youth.
AB  - BACKGROUND: Identifying risk factors for youth e-cigarette use is critical, given
      high rates of e-cigarette use and unknown health effects of long-term use. The
      current study examined whether an early age of onset of e-cigarette use mediates
      the association between impulsivity and e-cigarette frequency. METHODS: Cross
      sectional survey data of e-cigarette users (n=927) were collected from 8 high
      schools in southeastern Connecticut. The sample was 44.7% female (mean age 16.2
      [SD=1.2], mean age of e-cigarette onset 14.7 [SD=1.6]). Two domains of self
      reported, trait impulsivity were assessed using the abbreviated Barratt
      Impulsiveness Scale: impaired self-regulation (e.g., problems with concentration
      or self-control) and behavioral impulsivity (e.g., doing things without
      thinking). Mediation was tested with Mplus, and the model included school as a
      cluster variable and controlled for covariates related to e-cigarette use (i.e.,
      sex, age, race, peer use, and other tobacco products ever tried). RESULTS: The
      hypothesized mediation was supported for both domains of impulsivity (impaired
      self-regulation a1b=0.09, SE=0.02, 95%CI [0.03-0.14], p=.002; behavioral
      impulsivity a2b=0.07, SE=0.03, 95%CI [.01-.14], p=0.03). Specifically, impaired
      self-regulation (B=-0.33, SE=0.06, p<0.001) and behavioral impulsivity (B=-0.26,
      SE=0.11, p=0.02) predicted trying e-cigarettes at an earlier age, and earlier
      initiation was associated with more days of e-cigarette use in the past month (B=
      0.28, SE=0.08, p<0.001). CONCLUSIONS: Adolescents who endorse aspects of
      impulsivity, such as acting without thinking, are at greater risk for more
      frequent e-cigarette use through an early age of e-cigarette initiation. Further
      research is needed to evaluate these relationships longitudinally and to develop
      targeted e-cigarette interventions for impulsive youth.

PMID- 29055269
TI  - Decision making measured by the Iowa Gambling Task in alcohol use disorder and
      gambling disorder: a systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: Gambling disorder (GD) and alcohol use disorder (AD) have
      similar features, such as elevated impulsivity and decision-making deficits,
      which are directly linked to relapse and poor therapeutic outcomes. Our aim was
      to assess decision-making characteristics in GD and AD patients compared to
      healthy controls (HC) based on one of the most frequently used measures of
      decision-making: the Iowa Gambling Task (IGT). METHODS: In our systematic
      literature search of three databases, we identified 1198 empirical articles that
      mentioned decision-making deficits with the use of the IGT in patients diagnosed
      with either AD or GD. Possible effects were calculated using meta-analysis. In
      the end, 17 studies (including 1360 participants) were suitable for inclusion in
      the meta-analysis reporting data for 23 group contrasts. RESULTS: The random
      effects estimate indicated impaired IGT performance in both AD patients (N=500;
      d=-0.581, CI:-89.5<delta<-26.6%) and an even greater deficit in GD patients
      (N=292; d=-1.034, CI:-156.1<delta<50.7%) compared to HCs. Sampling variances were
      calculated for both AD (v1=0.0056) and GD groups (v2=0.0061), from which the z
      score was calculated (z=-21.0785; p<0.05), which indicates a statistically
      significant difference between AD and GD groups. No significant moderating
      effects of age, gender or education were found. CONCLUSIONS: There is enough
      evidence to support that decision-making deficit associated with addictive
      disorders, and that the deficit is more expressed in gambling disorder than in
      alcohol use disorder. Impaired decision-making plays an important part in poor
      therapeutic outcomes, thus provides a promising opportunity for cognitive
      intervention.

PMID- 29055270
TI  - Executive functioning, concern about falling and quadriceps strength mediate the
      relationship between impaired gait adaptability and fall risk in older people.
AB  - BACKGROUND: Reduced ability to adapt gait, particularly under challenging
      conditions, may be an important reason why older adults have an increased risk of
      falling. This study aimed to identify cognitive, psychological and physical
      mediators of the relationship between impaired gait adaptability and fall risk in
      older adults. METHODS: Fifty healthy older adults (mean+/-SD: 74+/-7years) were
      categorised as high or low fall risk, based on past falls and their performance
      in the Physiological Profile Assessment. High and low-risk groups were then
      compared in the gait adaptability test, i.e. an assessment of the ability to
      adapt gait in response to obstacles and stepping targets under single and dual
      task conditions. Quadriceps strength, concern about falling and executive
      function were also measured. RESULTS: The older adults who made errors on the
      gait adaptability test were 4.76 (95%CI=1.08-20.91) times more likely to be at
      high risk of falling. Furthermore, each standard deviation reduction in gait
      speed while approaching the targets/obstacle increased the odds of being at high
      risk of falling approximately three fold: single task - OR=3.10,95%CI=1.43-6.73;
      dual task - 3.42,95%CI=1.56-7.52. Executive functioning, concern about falling
      and quadriceps strength substantially mediated the relationship between the gait
      adaptability measures and fall risk status. CONCLUSION: Impaired gait
      adaptability is associated with high risk of falls in older adults. Reduced
      executive function, increased concern about falling and weaker quadriceps
      strength contribute significantly to this relationship. Training gait
      adaptability directly, as well as addressing the above mediators through
      cognitive, behavioural and physical training may maximise fall prevention
      efficacy.

PMID- 29055271
TI  - Neurocysticercosis as an infectious acquired epilepsy worldwide.
AB  - Aside from brain injury and genetic causes, there is emerging information on
      brain infection and inflammation as a common cause of epilepsy.
      Neurocysticercosis (NCC), the most common cause of epilepsy worldwide, is caused
      by brain cysts from the Taenia solium tapeworm. In this article, we provide a
      critical analysis of current and emerging information on the relationship between
      NCC infection and epilepsy occurrence. We searched PubMed and other databases for
      reports on the prevalence of NCC and incidence of epilepsy in certain regions
      worldwide. NCC is caused by brain cysts from the T. solium and related tapeworms.
      Many people with NCC infection may develop epilepsy but the rates are highly
      variable. MRI imaging shows many changes including localization of cysts as well
      as the host response to treatment. Epilepsy, in a subset of NCC patients, appears
      to be due to hippocampal sclerosis. Serologic and brain imaging profiles are
      likely diagnostic biomarkers of NCC infection and are also used to monitor the
      course of treatments. Limited access to these tools is a key limitation to
      identify and treat NCC-related epilepsy in places with high prevalence of this
      parasite infestation. Overall, NCC is a common infection in many patients with
      epilepsy worldwide. Additional clinical and animal studies could confirm common
      pathology of NCC as a postinfectious epilepsy that is curable.

PMID- 29055272
TI  - Engaging psychiatrists in the diagnosis of psychogenic nonepileptic seizures.
      What can they contribute?
AB  - PURPOSE: To investigate if psychiatrists could predict the diagnosis of
      psychogenic nonepileptic seizures (PNES) by reviewing videos of seizures of
      various types and to compare the accuracy and the criteria leading to the
      diagnosis used by psychiatrists with those used by epileptologists. METHODS: Four
      board-certified psychiatrists were asked to review 23 videos capturing
      representative events of 21 unselected consecutive patients admitted to an
      epilepsy center for long-term video-EEG monitoring. All raters were blind to EEG
      and clinical information. They were requested to (1) rate the videos for quality
      and content; (2) choose among four diagnoses: (a) epileptic seizures; (b) PNES;
      (c) Other nonepileptic seizures (syncope, movement disorder, migraine, etc.); (d)
      "Cannot Say"; and (3) explain in their own words the main reasons leading to the
      diagnosis of choice. The results were compared to those of four blind
      epileptologists who independently reviewed the same cases. The inter-rater
      reliability was tested with the Kappa statistic. RESULTS: All psychiatrists were
      concordant and correct in 3/23 video-events, compared to 8/23 among
      epileptologists. Despite widespread disagreement among themselves and frequent
      failures as a group, individual psychiatrists scored a comparable number of
      correct diagnoses as did individual epileptologists. The comments provided to
      justify the diagnosis of choice differed from neurologists, varied among raters,
      and reflected considerable attention to body movements and body language.
      CONCLUSION: Psychiatrists, as a group, are less reliable than neurologists in
      differentiating seizure types on video but, as individuals, can be quite accurate
      in making the correct diagnosis because they are more attuned to capture the
      subtleties of human behaviour, of subjective experiences, as the effects of
      hidden internal conflicts and can contribute a new lexicon in defining PNES.

PMID- 29055273
TI  - Dehydroepiandrosterone and cortisol/dehydroepiandrosterone ratios in dairy cattle
      with postpartum metritis.
AB  - Dehydroepiandrosterone (DHEA), a C19 steroid synthesized predominantly by the
      adrenal cortex, and its sulfated precursor (DHEAS) has antiglucocorticoid and
      immunoprotective properties. DHEA is important in modulating inflammatory
      responses; therefore, we hypothesized that DHEA concentrations might be altered
      in bovine postpartum metritis. DHEA, DHEAS, the cortisol/DHEA-ratio (C/D-ratio)
      and the DHEAS/DHEA ratio were determined in cows with and without clinical
      metritis subcategorized by the blood leukocyte numbers. Blood from the coccygeal
      vein of 37 pluriparous Holstein-Friesian cows was sampled 8.8+/-0.9days (mean+/
      SE) after calving. Based on clinical signs of metritis and leukocyte numbers
      (normal range 5-10*106/MUl), cows were classified as healthy with leukocyte
      numbers in the reference range (leukocyte normal; LNH=5954.17+/-302.4/MUl);
      suffering from metritis with normal leukocyte counts (LNM=7422.22+/-774.74/MUl);
      or metritis with leukopenia (LLM=3950+/-284.31/MUl P<0.01). Cows with metritis
      had higher DHEA concentrations than healthy cows (P<0.05). Notably, cows with
      both metritis and leukopenia displayed higher DHEA concentrations than cows with
      metritis and normal leukocyte numbers (DHEA LLM 8.15+/-3.09 vs. LNM 4.09+/
      1.82ng/ml, P<0.05). Cows with metritis and leukopenia also had lower C/D-ratios
      than healthy cows. In conclusion, DHEA and the cortisol/DHEA-ratio could
      represent an anti-inflammatory signal during prolonged inflammation of the
      reproductive tract in dairy cattle and may be a biomarker or prognostic indicator
      for evaluating disease severity, as seen in serious chronic illnesses in other
      species.

PMID- 29055274
TI  - Comparative study of 4D CTA and DSA for vascular assessment in moyamoya disease.
AB  - PURPOSE: To evaluate the vascular stenosis and collateral circulation in moyamoya
      disease using 4D CTA. METHODS: Two neuroradiologists evaluated 4D CTA and DSA for
      101 moyamoya patients. The performance of 4D CTA relative to DSA was determined
      using consistency checks (kappa values, 95% CI) and correlation analysis.
      RESULTS: The kappa values were 0.714 (modified Suzuki score), 0.846 (Houkin
      score), 0.594 (basicranial moyamoya vessels), 0.435 (posterior circulation
      collaterals) and 0.591 (ECA collaterals). The correlation coefficients were
      0.843, 0.872, 0.792, 0.635 and 0.797. CONCLUSIONS: 4D CTA showed strong
      consistency and correlation with DSA in the vascular stenosis score, but was
      insufficient in collateral circulation evaluation.

PMID- 29055275
TI  - Three-dimensional versus two-dimensional shear-wave elastography: Associations of
      mean elasticity values with prognostic factors and tumor subtypes of breast
      cancer.
AB  - PURPOSE: To explore associations between prognostic factors and subtypes of
      invasive breast cancer (IBC) and elasticity values using three-dimensional (3D)
      and two-dimensional (2D) shear-wave elastography (SWE). MATERIALS AND METHODS:
      Mean elasticity values (kPa) of 121 IBCs were measured using both 3D and 2D SWE.
      Associations between these values and prognostic factors and subtypes were
      analyzed using linear regression model. RESULTS: In both 3D and 2D SWE, larger
      size and presence of lymphovascular invasion were independent factors influencing
      higher mean elasticity on multivariate analyses (all p values<0.05). CONCLUSIONS:
      Using either 3D or 2D SWE, higher mean elasticity values are associated with poor
      prognostic factors of IBC.

PMID- 29055276
TI  - Nonadiabatic dynamics simulation of photoisomerization mechanism of the second
      stablest isomer of N-salicilydenemethylfurylamine.
AB  - The photoisomerization processes of the second stablest isomer in the aromatic
      Schiff base, N-salicilydenemethylfurylamine, in the gas phase have been studied
      by static electronic structure calculations and surface-hopping dynamics
      simulations based on the Zhu-Nakamura theory. Various stable structures are
      obtained in the optimization because of different orientations of methyl-furyl
      part with respect to the salicylaldimine part and different orientations of
      hydroxy group with respect to the benzene ring. Upon photoexcitation into the
      first excited state, bond isomerization in the salicylaldimine part is completely
      suppressed until the strong excited-state hydrogen bond is broken. The decay
      pathway involves two excited-state minima, one in cis-enol form and the other in
      cis-keto form. After the excited-state proton transfer, twists of bonds lead to a
      conical intersection between the ground and excited states. After internal
      conversion around a conical intersection, the molecule is stabilized in cis- or
      trans-keto form. If the reverse hydrogen transfer process occurs in the ground
      state, the molecule will finally end up in the cis-enol region. The cis-keto and
      trans-keto isomers are observed as photoproducts. According to our full
      dimensional nonadiabatic dynamics simulations, we find the excited-state
      intramolecular proton transfer and torsions of three single bonds in the chain to
      be responsible for photoisomerization of the second stablest isomer of N
      salicilydenemethylfurylamine.

PMID- 29055277
TI  - Structural, photophysical, and theoretical studies of imidazole-based excited
      state intramolecular proton transfer molecules.
AB  - Imidazole-based excited state intramolecular proton transfer (ESIPT) blue
      fluorescent molecules, 2-(1-(4-chlorophenyl)-4,5-diphenyl-1H-imidazol-2-yl)phenol
      (BHPI-Cl) and 2-(1-(4-bromophenyl)-4,5-diphenyl-1H-imidazol-2-yl)phenol (BHPI-Br)
      were designed and synthesized by Debus-Radziszewski method through a one-pot
      multicomponent reaction in high yield. The synthesized compounds were fully
      characterized by 1H NMR, 13C NMR, FT-IR, FT-Raman, GC-Mass, and elemental
      analysis. The molecular structures in single crystal lattice were studied by X
      ray crystallographic analysis. Because of the intramolecular hydrogen bonding,
      hydroxyphenyl group is planar to the central imidazole ring, while the other
      phenyl rings gave distorted conformations to the central heterocyclic ring. BHPI
      Cl and BHPI-Br molecules showed intense ESIPT fluorescence at 480nm, because the
      two twisted phenyl rings on 4- and 5-positions have reduced intermolecular
      interaction between adjacent molecules in each crystal through a head-to-tail
      packing manner. Quantum chemical calculations of energies were carried out by (TD
      )DFT using B3LYP/6-31G(d, p) basis set to predict the electronic absorption
      spectra of the compounds, and they showed good agreement between the
      computational and the experimental values. The thermal analyses of the
      synthesized molecules were also carried out by TGA/DSC method.

PMID- 29055278
TI  - Enhanced Sensitivity to Detection Nanomolar Level of Cu2+ Compared to
      Spectrophotometry Method by Functionalized Gold Nanoparticles: Design of Sensor
      Assisted by Exploiting First-order Data with Chemometrics.
AB  - A simple, sensitive and efficient colorimetric assay platform for the
      determination of Cu2+ was proposed with the aim of developing sensitive detection
      based on the aggregation of AuNPs in presence of a histamine H2-receptor
      antagonist (famotidine, FAM) as recognition site. This study is the first to
      demonstrate that the molar extinction coefficients of the complexes formed by FAM
      and Cu2+ are very low (by analyzing the chemometrics methods on the first order
      data arising from different metal to ligand ratio method), leading to the
      undesirable sensitivity of FAM-based assays. To resolve the problem of low
      sensitivity, the colorimetry method based on the Cu2+-induced aggregation of
      AuNPs functionalized with FAM was introduced. This procedure is accompanied by a
      color change from bright red to blue which can be observed with the naked eyes.
      Detection sensitivity obtained by the developed method increased about 100 fold
      compared with the spectrophotometry method. This sensor exhibited a good linear
      relation between the absorbance ratios at 670 to 520nm (A670/520) and the
      concentration in the range 2-110nM with LOD=0.76nM. The satisfactory analytical
      performance of the proposed sensor facilitates the development of simple and
      affordable UV-Vis chemosensors for environmental applications.

PMID- 29055280
TI  - Optical limiting properties of 3,5-dipyrenylvinyleneBODIPY dyes at 532nm.
AB  - The optical limiting (OL) properties of 3,5-dipyrenylvinyleneBODIPY dyes that
      contain both electron withdrawing and donating moieties have been investigated by
      using the z-scan technique at 532nm in the nanosecond pulse range. The extension
      of the pi-conjugation at the 3,5-positions with pyrenylvinylene groups results in
      a ca. 200nm red shift of the main BODIPY spectral band to ca. 700nm, so there is
      relatively weak absorbance at 532nm under ambient light conditions. Reverse
      saturable absorbance (RSA) profiles are observed in response to incident pulsed
      laser light that is consistent with a two photon absorption-assisted excited
      state absorption (ESA) mechanism in CH2Cl2 solution and when the dyes are
      embedded in poly(bisphenol carbonate A) (PBC) polymer thin films. This
      demonstrates that 3,5-divinyleneBODIPY dyes are potentially suitable for use in
      OL applications, since limiting threshold fluence (Ilim) values of below 0.95Jcm
      2 are observed when thin films are prepared.

PMID- 29055279
TI  - A molecularly imprinted dual-emission carbon dot-quantum dot mesoporous hybrid
      for ratiometric determination of anti-inflammatory drug celecoxib.
AB  - We report on a ratiometric fluorescent sensor based on dual-emission molecularly
      imprinted mesoporous silica embedded with carbon dots and CdTe quantum dots
      (mMIP@CDs/QDs) for celecoxib (CLX) as target molecule. The fluorescence of the
      embedded CDs is insensitive to the analyte while the green emissive QDs are
      selectively quenched by it. This effect is much stronger for the MIP than for the
      non-imprinted polymer, which indicates a good recognition ability of the
      mesoporous MIP. The hybrid sensor also exhibited good selectivity to CLX over
      other substances. The ratio of the intensity at two wavelengths (F550/F440)
      proportionally decreased with the increasing of CLX concentration in the range of
      0.08-0.90MUM. A detection limit as low as 57nM was achieved. Experimental results
      testified that this sensor was highly sensitive and selective for the detection
      of CLX in human serum samples.

PMID- 29055281
TI  - Application of wavelet and Fuorier transforms as powerful alternatives for
      derivative spectrophotometry in analysis of binary mixtures: A comparative study.
AB  - Two signal processing methods, namely, Continuous Wavelet Transform (CWT) and the
      second was Discrete Fourier Transform (DFT) were introduced as alternatives to
      the classical Derivative Spectrophotometry (DS) in analysis of binary mixtures.
      To show the advantages of these methods, a comparative study was performed on a
      binary mixture of Naltrexone (NTX) and Bupropion (BUP). The methods were compared
      by analyzing laboratory prepared mixtures of the two drugs. By comparing
      performance of the three methods, it was proved that CWT and DFT methods are more
      efficient and advantageous in analysis of mixtures with overlapped spectra than
      DS. The three signal processing methods were adopted for the quantification of
      NTX and BUP in pure and tablet forms. The adopted methods were validated
      according to the ICH guideline where accuracy, precision and specificity were
      found to be within appropriate limits.

PMID- 29055282
TI  - Do developmental temperatures affect redox level and lifespan in C. elegans
      through upregulation of peroxiredoxin?
AB  - Lifespan in poikilothermic organisms, such as Caenorhabditis elegans, can be
      substantially increased simply by decreasing growth temperature. To gain insights
      into the mechanistic underpinnings of this effect, we investigated the effects of
      temperature in development and adulthood on C. elegans lifespan. We found that
      worms exposed to 25 degrees C during development and shifted to 15 degrees C in
      adulthood exhibited an even longer lifespan than animals constantly kept at 15
      degrees C. Analysis of the in vivo redox status demonstrated that at 25 degrees
      C, C. elegans larvae have a more reduced redox state and higher Prdx-2 expression
      levels than animals raised at 15 degrees C. Worms lacking prdx-2 fail to show the
      additional lifespan extension upon shift from 25 degrees C to 15 degrees C and
      reveal a lifespan similar to prdx-2 worms always kept at 15 degrees C. These
      results suggest that transiently altering the in vivo redox state during
      development can have highly beneficial long-term consequences for organisms.

PMID- 29055284
TI  - Multiple Sampling and SAF-Fixative Triple-Faeces Testing for Dysbiosis and
      Pathogenic Infections of the Gastrointestinal Tract: Case Report.
AB  - The classic presentation of acute gastrointestinal (GI) parasitic infection
      including fever, diarrhea, nausea, and/or abdominal pain is not always a reliable
      measure. In these cases, parasitic infections require sensitive stool testing to
      be identified and treated effectively. The standard practice for stool analysis
      typically requires 3 separate stool specimens to be collected on 3 separate days
      to overcome the possibility of misdiagnosis due to intermittent shedding.
      Nonetheless, this practice is not often utilized due to very short periods of
      sample viability, which often leads to patient misdiagnosis. In this study, a
      patient with a history that eluded to possible acute GI parasitic infection, but
      without classic symptomology, was screened using a sodium acetate acetic acid
      formalin (SAF)-fixative triple-faeces test. Even though the patient's symptoms
      did not strongly suggest stool analysis, her history of travel was clinically
      relevant. The faeces test revealed the patient was positive for Blastocystis
      hominis, Dientamoeba fragilis trophs, Endolimax nana trophs, Entamoeba coli
      trophs, a-hemolytic Streptococcus, Enterobacter cloacae, Klebsiella pneumoniae,
      and yeast. Subsequently, the patient was treated for GI infection and received
      significant symptom relief. This case supports the concept that physicians should
      fully evaluate a patient's clinical presentation and symptomology, including
      history and environmental exposures, and include highly sensitive testing for
      proper evaluation of potential GI parasitic infections.

PMID- 29055285
TI  - Delayed Spontaneous Resorption of Lumbar Intervertebral Disc Herniation: A Case
      Report.
AB  - Background * Large intervertebral disc herniation is often managed with surgery,
      but it is not uncommon for spontaneous resorption of herniated disc material to
      occur. Although the majority of spontaneous disc resorption occurs in the acute
      phase, an unusual case of delayed intervertebral disc regression at 18 mo
      postonset is presented. Case Presentation * A 32-y-old female patient presented
      with acute low-back pain and pain in both legs a Korean medicine hospital
      specializing in spinal disorders. Massive intervertebral disc herniation was
      found on lumbar magnetic resonance imaging (MRI), and inguinal and genital pain
      and numbness was suggestive of risk of cauda equina syndrome. Although she was
      recommended for surgery, the patient steadfastly refused surgical intervention
      and continued to receive nonsurgical Korean medicine treatment. Imaging studies
      including computed tomography scans and MRIs were taken in consideration of
      possible spontaneous disc regression at 3 and 6 mo, and 1 y after onset of
      symptoms with no initial disc resorption. However, delayed spontaneous regression
      of most of the herniated disc material was observed at 18 mo, and the majority of
      pain symptoms and functional disability recovered up to 2 y postonset.
      Conclusions * Delayed intervertebral disc resorption was observed in a case of
      large disc herniation well past the acute phase, and there was noticeable time
      difference in resolution on MRI and subsequent improvement in pain and functional
      recovery.

PMID- 29055283
TI  - Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model
      of cancer-induced bone pain.
AB  - Cancer-induced bone pain (CIBP) is a frequent complication in patients suffering
      from bone metastases. Previous studies have demonstrated a pivotal role of
      reactive oxygen species (ROS) in inflammatory and neuropathic pain, and ROS
      scavengers exhibited potent antinociceptive effect. However, the role of spinal
      ROS remains unclear. In this study, we investigated the analgesic effect of two
      ROS scavengers in a well-established CIBP model. Our results found that
      intraperitoneal injection of N-tert-Butyl-alpha-phenylnitrone (PBN, 50 and
      100mg/kg) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and
      200mg/kg) significantly suppressed the established mechanical allodynia in CIBP
      rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic
      effect without tolerance. However, early treatment with PBN and Tempol failed to
      prevent the development of CIBP. Naive rats received repetitive injection of PBN
      and Tempol showed no significant change regarding the nociceptive responses.
      Finally, PBN and Tempol treatment notably suppressed the activation of spinal
      microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP
      by suppressing the activation of microglia in the spinal cord.

PMID- 29055286
TI  - In Defense of Progesterone: A Review of the Literature.
AB  - Context * The medical literature on the use of progesterone in postmenopausal
      women is often confusing and contradictory. Some physicians implicate natural
      progesterone in an increase in the risk of breast cancer. The chemical structure
      of natural progesterone (P4) is quite different from chemically altered,
      synthetic chemicals called progestins, which results in different actions at the
      cell level. Objective * The research team intended to review the literature to
      examine the benefits and safety of natural progesterone and determine whether it
      can cause an increase or decrease in breast cancer risk. Design * A review of the
      medical literature to examine the benefits and safety of natural progesterone as
      compared with synthetic progestins. Intervention * Studies examined compared
      controls not receiving hormone therapy with women receiving estrogen alone and in
      combination with natural progesterone and with various synthetic progestins, such
      as medroxyprogesterone acetate-the most commonly used synthetic progestin.
      Outcome Measures * Outcome measures included factors such as progression and
      survival of breast and other cancers and other epidemiological and laboratory
      data. Results * A meta-analysis of 3 studies involving 86 881 postmenopausal
      women reported that the use of natural progesterone was associated with a
      significantly lower risk of breast cancer compared with synthetic progestins.
      Anovulation and low levels of serum progesterone have been associated with a
      significantly higher risk of breast cancer in premenopausal women. Use of
      progesterone has been linked to lower rates of uterine and colon cancers and may
      also be useful in treating other cancers such as ovarian, melanoma, mesothelioma,
      and prostate. Progesterone may also be helpful in preventing cardiovascular
      disease and preventing and treating neurodegenerative conditions such a stroke
      and traumatic brain injury. Conclusions * Physicians should have no hesitation
      prescribing natural progesterone. The evidence is clear that progesterone does
      not cause breast cancer. Indeed, progesterone is protective and preventative of
      breast cancer.

PMID- 29055287
TI  - Efficacy and Tolerability of High-dose Pelargonium Extract in Patients With the
      Common Cold.
AB  - Context * The common cold (CC) is usually caused by a viral infection.
      Antibiotics are often prescribed unnecessarily for it, although no evidence
      exists for any benefit in the CC. Effective alternatives are needed. Objective *
      The study intended to evaluate the efficacy of 7630, a proprietary extract of
      Pelargonium sidoides, the active ingredient in umckaloabo, compared with a
      placebo for the treatment of the CC. Design * This was a prospective, double
      blind, parallel-group, placebo-controlled, phase 3 clinical trial (RCT), with an
      adaptive group-sequential design with 2 parts, both of which were 2-arm trials.
      The first used a standard dose (SD) of 3 * 30 drops per day of the active
      medication and the second used a high dose (HD) of 3 * 60 drops per day of the
      active medication, against 3 * 30 drops per day and 3 * 60 drops per day of a
      placebo, respectively. Setting * The study took place in 8 outpatient departments
      affiliated with hospitals. Participants * For the entire study, 207 adults with
      predefined cold symptoms that had been present for 24 to 48 h prior were included
      in the study, with 103 participating in the SD part and 104 participating in the
      HD part. Intervention * In the HD part, as covered in this article, the
      intervention group received treatment with 3 * 60 drops per day of the active
      medication and the control group received a placebo (control group), for a
      maximum period of 10 d. Outcome Measures * The primary outcome measure was the
      sum of differences in the cold intensity score (CIS) from day 1 to day 3 and from
      day 1 to day 5, defined as the sum of the symptom intensity differences (SSID).
      The criteria for the secondary outcome, efficacy, were (1) diverse response
      criteria according to the total CIS; (2) changes in individual CIS symptoms; (3)
      changes in further cold-relevant symptoms; (4) ability to work; (5) activity
      level; (6) general well-being; (7) health-related quality of life-the EuroQol
      questionnaire with 5 dimensions (EQ-5D), including the visual analogue scale EQ
      VAS; (8) time until onset of treatment effect; (9) treatment outcome; and (10)
      satisfaction with treatment. Results * From baseline to day 5, the mean CIS
      decreased by 11.2 +/- 4.8 points for the 7630 group and 6.3 +/- 4.7 points for
      the control group. The mean SSID was 16.0 +/- 7.6 points for the control group (P
      < .0001). After 10 d, 90.4% of the group receiving the active medication and
      21.2% of the control group were clinically cured (P < .0001). In the treatment
      group, participants' inability to work was significantly lower, with a mean
      duration of 6.4 +/- 1.6 d vs 8.3 +/- 2.1 d for the control group (P < .0001), and
      treatment outcome-complete recovery or major improvement-was significantly better
      at day 5 for the active treatment group compared with the control group (P <
      .0001). Mild-to-moderate adverse events-all nonserious-occurred in 15.4% of those
      receiving active treatment vs in 5.8% for the control group. Conclusions * The
      active medication is an effective, well tolerated, and safe treatment for the CC.
      It significantly reduces the severity of symptoms and shortens the duration of
      the disease.

PMID- 29055288
TI  - Osteoinductive Effects of Cyplexinol in the Management of Osteoporosis: A Case
      Series.
AB  - Aims * A case study was conducted on a subject with a history of documented bone
      loss and the observed outcome of bone mineral density (BMD) changes when
      utilizing supplementation with Cyplexinol, a natural bone morphogenetic protein
      complex. Method and Results * A case of osteoporosis was reviewed with pertinent
      medical history and dual energy X-ray absorptiometry history described both pre-
      and postsupplementation. Results demonstrated a significant change in bone
      density parameter for the individual when the bone support supplement,
      Cyplexinol, was used. Given this promising initial result, 3 additional cases
      were reviewed for potential replication and generalizability. Results showed a
      range of positive bone density changes of 18.5% to 63.63% during a
      supplementation period of 2 to 5 y. Conclusions * Cyplexinol may effectively
      manage BMD loss experienced during osteoporosis, though more studies are
      warranted with larger samples to replicate these findings. Given that
      administration of Cyplexinol was found to improve density scores in both mild and
      severe cases, despite the extent of the patient's history of documented bone
      loss, Cyplexinol has a more diverse range of applicability than prescription
      medications, suggesting the first, natural alternative to bisphosphonates,
      hormone replacement therapies and antireceptor activator of nuclear factor kappa
      B ligand (anti-RANKL) agents. Furthermore, due to Cyplexinol's safety profile of
      no known side effects, it may be the ideal long-term strategy for individuals
      with bone loss and a possible preventative agent for individuals with known risk
      factors (eg, cigarette use, alcohol and carbonated drink usage, calcium
      deficiency, and family history) for osteoporosis. Although a larger pool of
      subjects is necessary to further support Cyplexinol's role in managing
      osteoporosis, these data are consistent with other studies examining the benefits
      of Cyplexinol's protein complex on BMD loss as a potential new, orally
      bioavailable therapeutic for the effective treatment of osteoporosis.

PMID- 29055289
TI  - Trends in incidence and associated risk factors of suicide mortality among breast
      cancer patients.
AB  - OBJECTIVE: Breast cancer patients are associated with an increased risk for
      committing suicide. The purpose of this study was to study the trends in the
      incidence of suicide mortality and identify pertinent risk factors among patients
      with breast cancer. METHODS: A retrospective examination of the Surveillance
      Epidemiology and End Results database between years 1973 and 2013 was performed.
      RESULTS: Overall, 474 128 patients were identified of which 773 had committed
      suicide. There were no significant differences in the incidence of suicide
      mortality over the last 3 decades (1984-1993: 0.14%, 1994-2003: 0.16%, 2004-2013:
      0.17%, P = 0.173). On logistic regression, younger age (<30 y: OR 6.34, 95% CI:
      1.98-20.33, P = 0.002; 30-49 y: OR 10.64, 95% CI: 7.97-14.2, P < 0.001; 50-69 y:
      OR 4.7, 95% CI: 3.64-6.07, P < 0.001), male sex (OR 4.34, 95% CI: 2.57-7.31, P <
      0.001), nonwhite-nonblack race (OR 1.39, 95% CI: 1.01-1.91, P = 0.046), marital
      status (single: OR 1.35, 95% CI: 1.04-1.76, P = 0.024;
      separated/divorced/widowed: OR 1.25, 95% CI: 1.01-1.55, P = 0.043), undergoing
      surgery (OR 2.13, 95% CI: 1.23-3.67, P = 0.007), and short-time elapsed from
      diagnosis (first year: OR 4.67, 95% CI: 3.39-6.42, P < 0.001; second year: OR
      2.35, 95% CI: 1.69-3.27, P < 0.001) were independent risk factors of suicide
      mortality. CONCLUSIONS: There have been no identifiable improvements in
      preventing suicide mortality in the United States. Younger age, male sex, race,
      marital status, and undergoing surgery are independent risk factors for
      committing suicide, especially in the first year after diagnosis.

PMID- 29055290
TI  - A qualitative meta-synthesis examining the role of women in African American
      men's prostate cancer screening and treatment decision making.
AB  - OBJECTIVE: Being an African American man is a risk factor for prostate cancer,
      and there is little consensus about the use of screening, early detection, and
      the efficacy of treatment for the disease. In this context, this systematic
      review examines the roles women, particularly wives, play in African American
      men's prostate cancer screening and treatment decision making. METHODS: We
      searched OVID Medline (R), CINAHL (EBSCO), PsychInfo (EBSCO), PubMED, Cochrane
      Library, ERIC (Firstsearch), and Web of Science to identify peer-reviewed
      articles published between 1980 and 2016 that reported qualitative data about
      prostate cancer screening, diagnosis, or treatment in African American men. We
      conducted a systematic review of the literature using study appraisal and
      narrative synthesis. RESULTS: Following Preferred Reporting Items for Systematic
      Reviews and Meta-analyses (PRISMA) guidelines for identifying and screening 1425
      abstracts and papers, we identified 10 papers that met our criteria. From our
      thematic meta-synthesis of the findings from these publications, we found that
      women played 3 key roles in African American men's decision making regarding
      prostate cancer screening, diagnosis, or treatment: counselor (ie, offering
      advice or information), coordinator (ie, promoting healthy behaviors and
      arranging or facilitating appointments), and confidant (ie, providing emotional
      support and reassurance). CONCLUSIONS: Women are often important confidants to
      whom men express their struggles, fears, and concerns, particularly those related
      to health, and they help men make appointments and understand medical advice.
      Better understanding women's supportive roles in promoting positive mental and
      physical outcomes may be key to developing effective interventions to improve
      African American men's decision making and satisfaction regarding prostate cancer
      screening and treatment.

PMID- 29055291
TI  - Origin of diverse time scales in the protein hydration layer solvation dynamics:
      A simulation study.
AB  - In order to inquire the microscopic origin of observed multiple time scales in
      solvation dynamics, we carry out several computer experiments. We perform
      atomistic molecular dynamics simulations on three protein-water systems, namely,
      lysozyme, myoglobin, and sweet protein monellin. In these experiments, we mutate
      the charges of the neighbouring amino acid side chains of certain natural probes
      (tryptophan) and also freeze the side chain motions. In order to distinguish
      between different contributions, we decompose the total solvation energy response
      in terms of various components present in the system. This allows us to capture
      the interplay among different self- and cross-energy correlation terms. Freezing
      the protein motions removes the slowest component that results from side chain
      fluctuations, but a part of slowness remains. This leads to the conclusion that
      the slow component approximately in the 20-80 ps range arises from slow water
      molecules present in the hydration layer. While the more than 100 ps component
      has multiple origins, namely, adjacent charges in amino acid side chains,
      hydrogen bonded water molecules and a dynamically coupled motion between side
      chain and water. In addition, the charges enforce a structural ordering of nearby
      water molecules and helps to form a local long-lived hydrogen bonded network.
      Further separation of the spatial and temporal responses in solvation dynamics
      reveals different roles of hydration and bulk water. We find that the hydration
      layer water molecules are largely responsible for the slow component, whereas the
      initial ultrafast decay arises predominantly (approximately 80%) due to the bulk.
      This agrees with earlier theoretical observations. We also attempt to rationalise
      our results with the help of a molecular hydrodynamic theory that was developed
      using classical time dependent density functional theory in a semi-quantitative
      manner.

PMID- 29055292
TI  - Transition path times reveal memory effects and anomalous diffusion in the
      dynamics of protein folding.
AB  - Recent single-molecule experiments probed transition paths of biomolecular
      folding and, in particular, measured the time biomolecules spend while crossing
      their free energy barriers. A surprising finding from these studies is that the
      transition barriers crossed by transition paths, as inferred from experimentally
      observed transition path times, are often lower than the independently determined
      free energy barriers. Here we explore memory effects leading to anomalous
      diffusion as a possible origin of this discrepancy. Our analysis of several
      molecular dynamics trajectories shows that the dynamics of common reaction
      coordinates used to describe protein folding is subdiffusive, at least at
      sufficiently short times. We capture this effect using a one-dimensional
      fractional Brownian motion (FBM) model, in which the system undergoes a
      subdiffusive process in the presence of a potential of mean force, and show that
      this model yields much broader distributions of transition path times with
      stretched exponential long-time tails. Without any adjustable parameters, these
      distributions agree well with the transition path times computed directly from
      protein trajectories. We further discuss how the FBM model can be tested
      experimentally.

PMID- 29055293
TI  - The diffusion of a Ga atom on GaAs(001)beta2(2 * 4): Local superbasin kinetic
      Monte Carlo.
AB  - We use first-principles density-functional theory to characterize the binding
      sites and diffusion mechanisms for a Ga adatom on the GaAs(001)beta2(2 * 4)
      surface. Diffusion in this system is a complex process involving eleven unique
      binding sites and sixteen different hops between neighboring binding sites. Among
      the binding sites, we can identify four different superbasins such that the
      motion between binding sites within a superbasin is much faster than hops exiting
      the superbasin. To describe diffusion, we use a recently developed local
      superbasin kinetic Monte Carlo (LSKMC) method, which accelerates a conventional
      kinetic Monte Carlo (KMC) simulation by describing the superbasins as absorbing
      Markov chains. We find that LSKMC is up to 4300 times faster than KMC for the
      conditions probed in this study. We characterize the distribution of exit times
      from the superbasins and find that these are sometimes, but not always,
      exponential and we characterize the conditions under which the superbasin exit
      time distribution should be exponential. We demonstrate that LSKMC simulations
      assuming an exponential superbasin exit-time distribution yield the same
      diffusion coefficients as conventional KMC.

PMID- 29055294
TI  - Nucleation and growth of copper selective-area atomic layer deposition on
      palladium nanostructures.
AB  - The nucleation and growth of copper atomic layer deposition (ALD) on palladium
      have been investigated for applications in nanoscale devices. Palladium
      nanostructures were fabricated by electron beam lithography and range in size
      from 250 nm to 5 MUm, prepared on oxidized silicon wafers. Copper ALD using
      Cu(thd)2(s) and H2(g) as reactants was carried out to selectively deposit copper
      on palladium seeded regions to the exclusion of surrounding oxide surfaces.
      Nuclei sizes and densities have been quantified by scanning electron microscopy
      for different growth conditions. It is found that growth occurs via island growth
      at temperatures of 150-190  degrees C and alloy growth at temperatures above 210 
      degrees C. In the lower temperature window, nucleation density increases with
      decreasing temperature, reaching a maximum of 4.8 +/- 0.2 * 109/cm2 at 150 
      degrees C, but growth is too slow for significant deposition at the lowest
      temperatures. At higher temperatures, individual nuclei cannot be quantified due
      to extensive mixing of copper and palladium layers. For the lower temperatures
      where nuclei can be quantified, rates of nucleation and growth are enhanced at
      high H2 partial pressures. At the smallest length scales, conformality of the
      deposited over-layers is limited by a finite nuclei density and evolving grain
      structure that cause distortion of the original nanostructure shape during
      growth.

PMID- 29055295
TI  - Effects of collision energy and vibrational excitation of CH3+ cations on its
      reactivity with hydrocarbons: But-2-yne CH3CCCH3 as reagent partner.
AB  - The methyl carbocation is ubiquitous in gaseous environments, such as planetary
      ionospheres, cometary comae, and the interstellar medium, as well as combustion
      systems and plasma setups for technological applications. Here we report on a
      joint experimental and theoretical study on the mechanism of the reaction CH3+ +
      CH3CCCH3 (but-2-yne, also known as dimethylacetylene), by combining guided ion
      beam mass spectrometry experiments with ab initio calculations of the potential
      energy hypersurface. Such a reaction is relevant in understanding the chemical
      evolution of Saturn's largest satellite, Titan. Two complementary setups have
      been used: in one case, methyl cations are generated via electron ionization,
      while in the other case, direct vacuum ultraviolet photoionization with
      synchrotron radiation of methyl radicals is used to study internal energy effects
      on the reactivity. Absolute reactive cross sections have been measured as a
      function of collision energy, and product branching ratios have been derived. The
      two most abundant products result from electron and hydride transfer, occurring
      via direct and barrierless mechanisms, while other channels are initiated by the
      electrophilic addition of the methyl cation to the triple bond of but-2-yne.
      Among the minor channels, special relevance is placed on the formation of C5H7+,
      stemming from H2 loss from the addition complex. This is the only observed
      condensation product with the formation of new C-C bonds, and it might represent
      a viable pathway for the synthesis of complex organic species in astronomical
      environments and laboratory plasmas.

PMID- 29055296
TI  - The opposing effects of isotropic and anisotropic attraction on association
      kinetics of proteins and colloids.
AB  - The association and dissociation of particles via specific anisotropic
      interactions is a fundamental process, both in biology (proteins) and in soft
      matter (colloidal patchy particles). The presence of alternative binding sites
      can lead to multiple productive states and also to non-productive "decoy" or
      intermediate states. Besides anisotropic interactions, particles can experience
      non-specific isotropic interactions. We employ single replica transition
      interface sampling to investigate how adding a non-productive binding site or a
      nonspecific isotropic interaction alters the dimerization kinetics of a generic
      patchy particle model. The addition of a decoy binding site reduces the
      association rate constant, independent of the site's position, while adding an
      isotropic interaction increases it due to an increased rebinding probability.
      Surprisingly, the association kinetics becomes non-monotonic for a tetramer
      complex formed by multivalent patchy particles. While seemingly identical to two
      particle binding with a decoy state, the cooperativity of binding multiple
      particles leads to a kinetic optimum. Our results are relevant for the
      understanding and modeling of biochemical networks and self-assembly processes.

PMID- 29055297
TI  - Rock climbing: A local-global algorithm to compute minimum energy and minimum
      free energy pathways.
AB  - The calculation of minimum energy or minimum free energy paths is an important
      step in the quantitative and qualitative studies of chemical and physical
      processes. The computations of these coordinates present a significant challenge
      and have attracted considerable theoretical and computational interest. Here we
      present a new local-global approach to study reaction coordinates, based on a
      gradual optimization of an action. Like other global algorithms, it provides a
      path between known reactants and products, but it uses a local algorithm to
      extend the current path in small steps. The local-global approach does not
      require an initial guess to the path, a major challenge for global pathway
      finders. Finally, it provides an exact answer (the steepest descent path) at the
      end of the calculations. Numerical examples are provided for the Mueller
      potential and for a conformational transition in a solvated ring system.

PMID- 29055299
TI  - Comment on "A new parametrizable model of molecular electronic structure" [J.
      Chem. Phys. 135, 134120 (2011)].

PMID- 29055298
TI  - Communication: Master equations for electron transport: The limits of the
      Markovian limit.
AB  - Master equations are increasingly popular for the simulation of time-dependent
      electronic transport in nanoscale devices. Several recent Markovian approaches
      use "extended reservoirs"-explicit degrees of freedom associated with the
      electrodes-distinguishing them from many previous classes of master equations.
      Starting from a Lindblad equation, we develop a common foundation for these
      approaches. Due to the incorporation of explicit electrode states, these methods
      do not require a large bias or even "true Markovianity" of the reservoirs.
      Nonetheless, their predictions are only physically relevant when the Markovian
      relaxation is weaker than the thermal broadening and when the extended reservoirs
      are "sufficiently large," in a sense that we quantify. These considerations hold
      despite complete positivity and respect for Pauli exclusion at any relaxation
      strength.

PMID- 29055300
TI  - Stochastic surface walking reaction sampling for resolving heterogeneous
      catalytic reaction network: A revisit to the mechanism of water-gas shift
      reaction on Cu.
AB  - Heterogeneous catalytic reactions on surface and interfaces are renowned for
      ample intermediate adsorbates and complex reaction networks. The common practice
      to reveal the reaction mechanism is via theoretical computation, which locates
      all likely transition states based on the pre-guessed reaction mechanism. Here we
      develop a new theoretical method, namely, stochastic surface walking (SSW)-Cat
      method, to resolve the lowest energy reaction pathway of heterogeneous catalytic
      reactions, which combines our recently developed SSW global structure
      optimization and SSW reaction sampling. The SSW-Cat is automated and massively
      parallel, taking a rough reaction pattern as input to guide reaction search. We
      present the detailed algorithm, discuss the key features, and demonstrate the
      efficiency in a model catalytic reaction, water-gas shift reaction on Cu(111) (CO
      + H2O -> CO2 + H2). The SSW-Cat simulation shows that water dissociation is the
      rate-determining step and formic acid (HCOOH) is the kinetically favorable
      product, instead of the observed final products, CO2 and H2. It implies that CO2
      and H2 are secondary products from further decomposition of HCOOH at high
      temperatures. Being a general purpose tool for reaction prediction, the SSW-Cat
      may be utilized for rational catalyst design via large-scale computations.

PMID- 29055301
TI  - Characterization of the [18.28]0--a3Delta1 (0,0) band of tantalum nitride, TaN.
AB  - The [18.28]0--a3Delta1 (0,0) band near 647 nm of tantalum nitride, TaN, has been
      recorded and analyzed field-free and in the presence of static electric and
      magnetic fields. The fine and hyperfine parameters for the a3Delta1 and [18.28]0-
      states are determined. The 181Ta(I = 7/2) axial nuclear electric quadrupole
      coupling constant, eQq0, and the effective magnetic hyperfine coupling constant,
      h1, are used to garner insight into the nature of electronic states. The Stark
      tuning of the P(2) and Q(1) lines was analyzed to determine the molecular frame
      permanent electric dipole moment, MU->el, for the a3Delta1 state of 4.49 +/- 0.09
      D. The Zeeman effect on the P(1) line was analyzed to determine an upper limit of
      the magnetic moment, MU->m, for the a3Delta1 state. Scalar-relativistic coupled
      cluster calculations for eQq0 and MU->el of the a3Delta1 state are also reported
      and compared with experimental results. The determined properties are compared
      with the predicted values and the implication of the proposed scheme for
      determination of the 181Ta magnetic quadrupole moment is discussed.

PMID- 29055302
TI  - Interrogating the Becke'05 density functional for non-locality information.
AB  - In two papers, Becke [J. Chem. Phys. 119, 2972 (2003) and J. Chem. Phys. 122,
      064101 (2005)] introduced Kohn-Sham density-functional approximations for static
      and dynamical correlation to be partnered with 100 percent exactly computed
      exchange. Known as "B05," this was the first non-local correlation model designed
      to work with the full non-locality of exact (or Hartree-Fock) exchange. Non
      locality issues, often referred to as the "delocalization" problem, are among the
      most vexing problems in density-functional theory today. How much exact exchange
      should be used in a hybrid functional? What value of the range parameter should
      be used in a long-range corrected functional? Questions such as these abound, and
      the answers are system dependent. The physics of non-locality is built into the
      B05 functional in a natural way, and one wonders, therefore, if B05 might provide
      a mechanism to answer such questions. Here we explore a variational procedure,
      "B05min," to do so. We compute dipole moments of 52 small molecules and find that
      B05min delivers better moments than parent hybrid and long-range corrected
      functionals. Furthermore, B05min provides a priori optimum exact-exchange mixing
      fractions and range parameters for the parent functionals, whose values agree
      with literature values fit to experimental data.

PMID- 29055303
TI  - An asymmetric mesoscopic model for single bulges in RNA.
AB  - Simple one-dimensional DNA or RNA mesoscopic models are of interest for their
      computational efficiency while retaining the key elements of the molecular
      interactions. However, they only deal with perfectly formed DNA or RNA double
      helices and consider the intra-strand interactions to be the same on both
      strands. This makes it difficult to describe highly asymmetric structures such as
      bulges and loops and, for instance, prevents the application of mesoscopic models
      to determine RNA secondary structures. Here we derived the conditions for the
      Peyrard-Bishop mesoscopic model to overcome these limitations and applied it to
      the calculation of single bulges, the smallest and simplest of these asymmetric
      structures. We found that these theoretical conditions can indeed be applied to
      any situation where stacking asymmetry needs to be considered. The full set of
      parameters for group I RNA bulges was determined from experimental melting
      temperatures using an optimization procedure, and we also calculated average
      opening profiles for several RNA sequences. We found that guanosine bulges show
      the strongest perturbation on their neighboring base pairs, considerably reducing
      the on-site interactions of their neighboring base pairs.

PMID- 29055304
TI  - c-T phase diagram and Landau free energies of (AgAu)55 nanoalloy via neural
      network molecular dynamic simulations.
AB  - For understanding the structure, dynamics, and thermal stability of (AgAu)55
      nanoalloys, knowledge of the composition-temperature (c-T) phase diagram is
      essential due to the explicit dependence of properties on composition and
      temperature. Experimentally, generating the phase diagrams is very challenging,
      and therefore theoretical insight is necessary. We use an artificial neural
      network potential for (AgAu)55 nanoalloys. Predicted global minimum structures
      for pure gold and gold rich compositions are lower in energy compared to previous
      reports by density functional theory. The present work based on c-T phase
      diagram, surface area, surface charge, probability of isomers, and Landau free
      energies supports the enhancement of catalytic property of Ag-Au nanoalloys by
      incorporation of Ag up to 24% by composition in Au nanoparticles as found
      experimentally. The phase diagram shows that there is a coexistence temperature
      range of 70 K for Ag28Au27 compared to all other compositions. We propose the
      power spectrum coefficients derived from spherical harmonics as an order
      parameter to calculate Landau free energies.

PMID- 29055305
TI  - Nudged elastic band calculations accelerated with Gaussian process regression.
AB  - Minimum energy paths for transitions such as atomic and/or spin rearrangements in
      thermalized systems are the transition paths of largest statistical weight. Such
      paths are frequently calculated using the nudged elastic band method, where an
      initial path is iteratively shifted to the nearest minimum energy path. The
      computational effort can be large, especially when ab initio or electron density
      functional calculations are used to evaluate the energy and atomic forces. Here,
      we show how the number of such evaluations can be reduced by an order of
      magnitude using a Gaussian process regression approach where an approximate
      energy surface is generated and refined in each iteration. When the goal is to
      evaluate the transition rate within harmonic transition state theory, the
      evaluation of the Hessian matrix at the initial and final state minima can be
      carried out beforehand and used as input in the minimum energy path calculation,
      thereby improving stability and reducing the number of iterations needed for
      convergence. A Gaussian process model also provides an uncertainty estimate for
      the approximate energy surface, and this can be used to focus the calculations on
      the lesser-known part of the path, thereby reducing the number of needed energy
      and force evaluations to a half in the present calculations. The methodology is
      illustrated using the two-dimensional Muller-Brown potential surface and
      performance assessed on an established benchmark involving 13 rearrangement
      transitions of a heptamer island on a solid surface.

PMID- 29055306
TI  - An algorithm to locate optimal bond breaking points on a potential energy surface
      for applications in mechanochemistry and catalysis.
AB  - The reaction path of a mechanically induced chemical transformation changes under
      stress. It is well established that the force-induced structural changes of
      minima and saddle points, i.e., the movement of the stationary points on the
      original or stress-free potential energy surface, can be described by a Newton
      Trajectory (NT). Given a reactive molecular system, a well-fitted pulling
      direction, and a sufficiently large value of the force, the minimum configuration
      of the reactant and the saddle point configuration of a transition state collapse
      at a point on the corresponding NT trajectory. This point is called barrier
      breakdown point or bond breaking point (BBP). The Hessian matrix at the BBP has a
      zero eigenvector which coincides with the gradient. It indicates which force
      (both in magnitude and direction) should be applied to the system to induce the
      reaction in a barrierless process. Within the manifold of BBPs, there exist
      optimal BBPs which indicate what is the optimal pulling direction and what is the
      minimal magnitude of the force to be applied for a given mechanochemical
      transformation. Since these special points are very important in the context of
      mechanochemistry and catalysis, it is crucial to develop efficient algorithms for
      their location. Here, we propose a Gauss-Newton algorithm that is based on the
      minimization of a positively defined function (the so-called sigma-function). The
      behavior and efficiency of the new algorithm are shown for 2D test functions and
      for a real chemical example.

PMID- 29055307
TI  - The threshold algorithm: Description of the methodology and new developments.
AB  - Understanding the dynamics of complex systems requires the investigation of their
      energy landscape. In particular, the flow of probability on such landscapes is a
      central feature in visualizing the time evolution of complex systems. To obtain
      such flows, and the concomitant stable states of the systems and the generalized
      barriers among them, the threshold algorithm has been developed. Here, we
      describe the methodology of this approach starting from the fundamental concepts
      in complex energy landscapes and present recent new developments, the threshold
      minimization algorithm and the molecular dynamics threshold algorithm. For
      applications of these new algorithms, we draw on landscape studies of three
      disaccharide molecules: lactose, maltose, and sucrose.

PMID- 29055308
TI  - Non-equilibrium reactive flux: A unified framework for slow and fast reaction
      kinetics.
AB  - The flux formulation of reaction rate theory is recast in terms of the
      expectation value of the reactive flux with an initial condition that corresponds
      to a non-equilibrium, factorized reactant density. In the common case of slow
      reactive processes, the non-equilibrium expression reaches the plateau regime
      only slightly slower than the equilibrium flux form. When the reactants are
      described by a single quantum state, as in the case of electron transfer
      reactions, the factorized reactant density describes the true initial condition
      of the reactive process. In such cases, the time integral of the non-equilibrium
      flux expression yields the reactant population as a function of time, allowing
      characterization of the dynamics in cases where there is no clear separation of
      time scales and thus a plateau regime cannot be identified. The non-equilibrium
      flux offers a unified approach to the kinetics of slow and fast chemical
      reactions and is ideally suited to mixed quantum-classical methods.

PMID- 29055309
TI  - Reaction pathways in atomistic models of thin film growth.
AB  - The atomistic processes that form the basis of thin film growth often involve
      complex multi-atom movements of atoms or groups of atoms on or close to the
      surface of a substrate. These transitions and their pathways are often difficult
      to predict in advance. By using an adaptive kinetic Monte Carlo (AKMC) approach,
      many complex mechanisms can be identified so that the growth processes can be
      understood and ultimately controlled. Here the AKMC technique is briefly
      described along with some special adaptions that can speed up the simulations
      when, for example, the transition barriers are small. Examples are given of such
      complex processes that occur in different material systems especially for the
      growth of metals and metallic oxides.

PMID- 29055310
TI  - Communication: Is a coarse-grained model for water sufficient to compute Kapitza
      conductance on non-polar surfaces?
AB  - Coarse-grained models have increasingly been used in large-scale particle-based
      simulations. However, due to their lack of degrees of freedom, it is a priori
      unlikely that they straightforwardly represent thermal properties with the same
      accuracy as their atomistic counterparts. We take a first step in addressing the
      impact of liquid coarse-graining on interfacial heat conduction by showing that
      an atomistic and a coarse-grained model of water may yield similar values of the
      Kapitza conductance on few-layer graphene with interactions ranging from
      hydrophobic to mildly hydrophilic. By design the water models employed yield
      similar liquid layer structures on the graphene surfaces. Moreover, they share
      common vibration properties close to the surfaces and thus couple with the
      vibrations of graphene in a similar way. These common properties explain why they
      yield similar Kapitza conductance values despite their bulk thermal conductivity
      differing by more than a factor of two.

PMID- 29055311
TI  - Preface: Special Topic on Reaction Pathways.
AB  - This Special Topic Issue on Reaction Pathways collects original research articles
      illustrating the state of the art in the development and application of methods
      to describe complex chemical systems in terms of relatively simple mechanisms and
      collective coordinates. A broad range of applications is presented, spanning the
      sub-fields of biophysics and material science, in an attempt to showcase the
      similarities in the formulation of the approaches and highlight the different
      needs of the different application domains.

PMID- 29055312
TI  - A Markov state modeling analysis of sliding dynamics of a 2D model.
AB  - Non-equilibrium Markov State Modeling (MSM) has recently been proposed by
      Pellegrini et al. [Phys. Rev. E 94, 053001 (2016)] as a possible route to
      construct a physical theory of sliding friction from a long steady state
      atomistic simulation: the approach builds a small set of collective variables,
      which obey a transition-matrix-based equation of motion, faithfully describing
      the slow motions of the system. A crucial question is whether this approach can
      be extended from the original 1D small size demo to larger and more realistic
      size systems, without an inordinate increase of the number and complexity of the
      collective variables. Here we present a direct application of the MSM scheme to
      the sliding of an island made of over 1000 harmonically bound particles over a 2D
      periodic potential. Based on a totally unprejudiced phase space metric and
      without requiring any special doctoring, we find that here too the scheme allows
      extracting a very small number of slow variables, necessary and sufficient to
      describe the dynamics of island sliding.

PMID- 29055313
TI  - Ion aggregation in high salt solutions. VII. The effect of cations on the
      structures of ion aggregates and water hydrogen-bonding network.
AB  - Ions in high salt solutions have a strong propensity to form polydisperse ion
      aggregates with broad size and shape distributions. In a series of previous
      comparative investigations using femtosecond IR pump-probe spectroscopy,
      molecular dynamics simulation, and graph theoretical analysis, we have shown that
      there exists a morphological difference in the structures of ion aggregates
      formed in various salt solutions. As salt concentration increases, the ions in
      high salt solutions form either cluster-like structures excluding water molecules
      or network-like structures entwined with water hydrogen-bonding networks.
      Interestingly, such morphological characteristics of the ion aggregates have been
      found to be in correlation with the solubility limits of salts. An important
      question that still remains unexplored is why certain salts with different
      cations have notably different solubility limits in water. Here, carrying out a
      series of molecular dynamics simulations of aqueous salt solutions and analyzing
      the distributions and connectivity patterns of ion aggregates with a spectral
      graph analysis method, we establish the relationship between the salt solubility
      and the ion aggregate morphology with a special emphasis on the cationic effects
      on water structures and ion aggregation. We anticipate that the understanding of
      large scale ion aggregate structures revealed in this study will be critical for
      elucidating the specific ion effects on the solubility and conformational
      stability of co-solute molecules such as proteins in water.

PMID- 29055314
TI  - Predicting reaction coordinates in energy landscapes with diffusion anisotropy.
AB  - We consider a range of model potentials with metastable states undergoing
      molecular dynamics coupled to a thermal bath in the high friction regime and
      consider how the optimal reaction coordinate depends on the diffusion anisotropy.
      For this we use our recently proposed method "spectral gap optimization of order
      parameters (SGOOP)" [P. Tiwary and B. J. Berne, Proc. Natl. Acad. Sci. U. S. A.
      113, 2839 (2016)]. We show how available information about dynamical observables
      in addition to static information can be incorporated into SGOOP, which can then
      be used to accurately determine the "best" reaction coordinate for arbitrary
      anisotropies. We compare our results with transmission coefficient calculations
      and published benchmarks wherever applicable or available, respectively.

PMID- 29055315
TI  - Electronic energy transfer through non-adiabatic vibrational-electronic
      resonance. I. Theory for a dimer.
AB  - Non-adiabatic vibrational-electronic resonance in the excited electronic states
      of natural photosynthetic antennas drastically alters the adiabatic framework, in
      which electronic energy transfer has been conventionally studied, and suggests
      the possibility of exploiting non-adiabatic dynamics for directed energy
      transfer. Here, a generalized dimer model incorporates asymmetries between
      pigments, coupling to the environment, and the doubly excited state relevant for
      nonlinear spectroscopy. For this generalized dimer model, the vibrational tuning
      vector that drives energy transfer is derived and connected to decoherence
      between singly excited states. A correlation vector is connected to decoherence
      between the ground state and the doubly excited state. Optical decoherence
      between the ground and singly excited states involves linear combinations of the
      correlation and tuning vectors. Excitonic coupling modifies the tuning vector.
      The correlation and tuning vectors are not always orthogonal, and both can be
      asymmetric under pigment exchange, which affects energy transfer. For equal
      pigment vibrational frequencies, the nonadiabatic tuning vector becomes an anti
      correlated delocalized linear combination of intramolecular vibrations of the two
      pigments, and the nonadiabatic energy transfer dynamics become separable. With
      exchange symmetry, the correlation and tuning vectors become delocalized
      intramolecular vibrations that are symmetric and antisymmetric under pigment
      exchange. Diabatic criteria for vibrational-excitonic resonance demonstrate that
      anti-correlated vibrations increase the range and speed of vibronically resonant
      energy transfer (the Golden Rule rate is a factor of 2 faster). A partial trace
      analysis shows that vibronic decoherence for a vibrational-excitonic resonance
      between two excitons is slower than their purely excitonic decoherence.

PMID- 29055316
TI  - Infrared absorption spectra of partially deuterated methoxy radicals CH2DO and
      CHD2O isolated in solid para-hydrogen.
AB  - The investigation of partially deuterated methoxy radicals is important because
      the symmetry lowering from C3v to Cs provides new insights into the couplings
      between rovibronic states via Jahn-Teller and spin-orbit interactions. The
      vibrational spectrum of the partially deuterated methoxy radical CH2DO in a
      matrix of p-H2 has been recorded. This species was prepared by irradiating a p-H2
      matrix containing deuterated d1-nitritomethane (CH2DONO) at 3.3 K with laser
      light at 355 nm. The identification of the radical is based on the photochemical
      behavior of the precursor and comparison of observed vibrational wavenumbers and
      infrared (IR) intensities with those predicted from a refined quartic,
      curvilinear, internal coordinate force field calculated with the coupled-cluster
      singles and doubles with perturbative triples/cc-pVTZ method. CH2DO reacts with
      H2 with a rate coefficient (3.5 +/- 1.0) * 10-3 s-1. Predominantly c-CHDOH and a
      negligibly small amount of t-CHDOH were produced. This stereoselectivity results
      from the reaction H + Cs-CH2DOH, which was demonstrated by an additional
      experiment on irradiation of a CH2DOH/Cl2/p-H2 matrix with ultraviolet and IR
      light to induce the H + CH2DOH reaction; only c-CHDOH was observed from this
      experiment. Even though the energies of transition states and products for the
      formation of c-CHDOH and t-CHDOH differ by only ~10 cm-1, the selective formation
      of c-CHDOH can be explained by tunneling of the hydrogen atom via an optimal
      tunneling path. Similarly, the vibronic spectrum for the partially deuterated
      specie d2-methoxy radical (CHD2O) was obtained upon irradiation of d2
      nitritomethane (CHD2ONO) at 355 nm. Lines associated with the fundamental
      vibrational modes were observed and assigned; line positions agree with
      theoretically predicted vibrational wavenumbers. CHD2O reacts with H2 with a rate
      coefficient (6.0 +/- 1.4) * 10-3 s-1; CD2OH was produced as a major product
      because the barrier for the formation of CHDOH from H + CHD2OH is greater by ~400
      cm-1. Rate coefficients of the decays of CH3O, CH2DO, CHD2O, and CD3O and their
      corresponding potential energy surfaces are compared.

PMID- 29055317
TI  - Foundations and latest advances in replica exchange transition interface
      sampling.
AB  - Nearly 20 years ago, transition path sampling (TPS) emerged as an alternative
      method to free energy based approaches for the study of rare events such as
      nucleation, protein folding, chemical reactions, and phase transitions. TPS
      effectively performs Monte Carlo simulations with relatively short molecular
      dynamics trajectories, with the advantage of not having to alter the actual
      potential energy surface nor the underlying physical dynamics. Although the TPS
      approach also introduced a methodology to compute reaction rates, this approach
      was for a long time considered theoretically attractive, providing the exact same
      results as extensively long molecular dynamics simulations, but still expensive
      for most relevant applications. With the increase of computer power and
      improvements in the algorithmic methodology, quantitative path sampling is
      finding applications in more and more areas of research. In particular, the
      transition interface sampling (TIS) and the replica exchange TIS (RETIS)
      algorithms have, in turn, improved the efficiency of quantitative path sampling
      significantly, while maintaining the exact nature of the approach. Also, open
      source software packages are making these methods, for which implementation is
      not straightforward, now available for a wider group of users. In addition, a
      blooming development takes place regarding both applications and algorithmic
      refinements. Therefore, it is timely to explore the wide panorama of the new
      developments in this field. This is the aim of this article, which focuses on the
      most efficient exact path sampling approach, RETIS, as well as its recent
      applications, extensions, and variations.

PMID- 29055318
TI  - Superatomic states in nickel clusters: Revising the prospects for transition
      metal based superatoms.
AB  - The geometries and electronic structures of small Ninz clusters (n = 8, 9, 10) (z
      = 0, +/-1, 2) have been elucidated for a range of multiplicities for each cluster
      size and charge, using density functional theory methods. These clusters have
      been found to conform in part to the existing superatomic model, with each
      cluster having a filled superatomic S-orbital, filled or partially filled
      superatomic P-orbitals, and empty or partially filled superatomic D-orbitals.
      Despite local states of mixed symmetry being present in the immediate vicinity of
      the Fermi energy, the addition or removal of a single electron from these systems
      causes a significant shift in the relative energies of the superatomic orbitals.
      In addition, this study demonstrates the possibility for d-electrons to
      contribute into superatomic orbitals to a greater or lesser extent, depending on
      the local environment. In summary, these observations lead to the prospect of a
      predictive model for electronic shell closings in some transition metal cluster
      systems.

PMID- 29055319
TI  - Transformation of topologically close-packed beta-W to body-centered cubic alpha
      W: Comparison of experiments and computations.
AB  - The enthalpy and activation energy for the transformation of the metastable form
      of tungsten, beta-W, which has the topologically close-packed A15 structure
      (space group Pm3-n), to equilibrium alpha-W, which is body-centered cubic (A2,
      space group Im3-m), was measured using differential scanning calorimetry. The
      beta-W films were 1 MUm-thick and were prepared by sputter deposition in argon
      with a small amount of nitrogen. The transformation enthalpy was measured as -8.3
      +/- 0.4 kJ/mol (-86 +/- 4 meV/atom) and the transformation activation energy as
      2.2 +/- 0.1 eV. The measured enthalpy was found to agree well with the difference
      in energies of alpha and beta tungsten computed using density functional theory,
      which gave a value of -82 meV/atom for the transformation enthalpy. A calculated
      concerted transformation mechanism with a barrier of 0.4 eV/atom, in which all
      the atoms in an A15 unit cell transform into A2, was found to be inconsistent
      with the experimentally measured activation energy for any critical nucleus
      larger than two A2 unit cells. Larger calculations of eight A15 unit cells
      spontaneously relax to a mechanism in which part of the supercell first
      transforms from A15 to A2, creating a phase boundary, before the remaining A15
      transforms into the A2 phase. Both calculations indicate that a nucleation and
      growth mechanism is favored over a concerted transformation. More consistent with
      the experimental activation energy was that of a calculated local transformation
      mechanism at the A15-A2 phase boundary, computed as 1.7 eV using molecular
      dynamics simulations. This calculated phase transformation mechanism involves
      collective rearrangements of W atoms in the disordered interface separating the
      A15 and A2 phases.

PMID- 29055320
TI  - Combining short- and long-range fluorescence reporters with simulations to
      explore the intramolecular dynamics of an intrinsically disordered protein.
AB  - Intrinsically disordered proteins (IDPs) are increasingly recognized as a class
      of molecules that can exert essential biological functions even in the absence of
      a well-defined three-dimensional structure. Understanding the conformational
      distributions and dynamics of these highly flexible proteins is thus essential
      for explaining the molecular mechanisms underlying their function. Single
      molecule fluorescence spectroscopy in combination with Forster resonance energy
      transfer (FRET) is a powerful tool for probing intramolecular distances and the
      rapid long-range distance dynamics in IDPs. To complement the information from
      FRET, we combine it with photoinduced electron transfer (PET) quenching to
      monitor local loop-closure kinetics at the same time and in the same molecule.
      Here we employed this combination to investigate the intrinsically disordered N
      terminal domain of HIV-1 integrase. The results show that both long-range
      dynamics and loop closure kinetics on the sub-microsecond time scale can be
      obtained reliably from a single set of measurements by the analysis with a
      comprehensive model of the underlying photon statistics including both FRET and
      PET. A more detailed molecular interpretation of the results is enabled by direct
      comparison with a recent extensive atomistic molecular dynamics simulation of
      integrase. The simulations are in good agreement with experiment and can explain
      the deviation from simple models of chain dynamics by the formation of persistent
      local secondary structure. The results illustrate the power of a close
      combination of single-molecule spectroscopy and simulations for advancing our
      understanding of the dynamics and detailed mechanisms in unfolded and
      intrinsically disordered proteins.

PMID- 29055321
TI  - All-atom calculation of protein free-energy profiles.
AB  - The Bias Functional (BF) approach is a variational method which enables one to
      efficiently generate ensembles of reactive trajectories for complex biomolecular
      transitions, using ordinary computer clusters. For example, this scheme was
      applied to simulate in atomistic detail the folding of proteins consisting of
      several hundreds of amino acids and with experimental folding time of several
      minutes. A drawback of the BF approach is that it produces trajectories which do
      not satisfy microscopic reversibility. Consequently, this method cannot be used
      to directly compute equilibrium observables, such as free energy landscapes or
      equilibrium constants. In this work, we develop a statistical analysis which
      permits us to compute the potential of mean-force (PMF) along an arbitrary
      collective coordinate, by exploiting the information contained in the reactive
      trajectories calculated with the BF approach. We assess the accuracy and
      computational efficiency of this scheme by comparing its results with the PMF
      obtained for a small protein by means of plain molecular dynamics.

PMID- 29055322
TI  - Multiple exciton generation in chiral carbon nanotubes: Density functional theory
      based computation.
AB  - We use a Boltzmann transport equation (BE) to study time evolution of a photo
      excited state in a nanoparticle including phonon-mediated exciton relaxation and
      the multiple exciton generation (MEG) processes, such as exciton-to-biexciton
      multiplication and biexciton-to-exciton recombination. BE collision integrals are
      computed using Kadanoff-Baym-Keldysh many-body perturbation theory based on
      density functional theory simulations, including exciton effects. We compute
      internal quantum efficiency (QE), which is the number of excitons generated from
      an absorbed photon in the course of the relaxation. We apply this approach to
      chiral single-wall carbon nanotubes (SWCNTs), such as (6,2) and (6,5). We predict
      efficient MEG in the (6,2) and (6,5) SWCNTs within the solar spectrum range
      starting at the 2Eg energy threshold and with QE reaching ~1.6 at about 3Eg,
      where Eg is the electronic gap.

PMID- 29055323
TI  - Assessment of mean-field microkinetic models for CO methanation on stepped metal
      surfaces using accelerated kinetic Monte Carlo.
AB  - First-principles screening studies aimed at predicting the catalytic activity of
      transition metal (TM) catalysts have traditionally been based on mean-field (MF)
      microkinetic models, which neglect the effect of spatial correlations in the
      adsorbate layer. Here we critically assess the accuracy of such models for the
      specific case of CO methanation over stepped metals by comparing to spatially
      resolved kinetic Monte Carlo (kMC) simulations. We find that the typical low
      diffusion barriers offered by metal surfaces can be significantly increased at
      step sites, which results in persisting correlations in the adsorbate layer. As a
      consequence, MF models may overestimate the catalytic activity of TM catalysts by
      several orders of magnitude. The potential higher accuracy of kMC models comes at
      a higher computational cost, which can be especially challenging for surface
      reactions on metals due to a large disparity in the time scales of different
      processes. In order to overcome this issue, we implement and test a recently
      developed algorithm for achieving temporal acceleration of kMC simulations. While
      the algorithm overall performs quite well, we identify some challenging cases
      which may lead to a breakdown of acceleration algorithms and discuss possible
      directions for future algorithm development.

PMID- 29055324
TI  - Single-active-electron analysis of laser-polarization effects on atomic/molecular
      multiphoton excitation.
AB  - We theoretically explore the effects of optical ellipticity on single-active
      electron multiphoton excitation in atoms and (nearly) spherical molecules
      irradiated by intense polarized laser fields. This work was motivated by the
      experimental and theoretical studies of Hertel et al. [Phys. Rev. Lett. 102,
      023003 (2009) and Phys. Rev. A 79, 053414 (2009)], who reported pronounced
      changes in the near-infrared-induced ion yields of xenon and C60 as a function of
      ellipticity (in particular, yield reduction for circular polarization) at low
      light intensities and derived a perturbative cross section formula to describe
      such polarization effects by assuming that the excited-state energies and radial
      transition electric dipole moments of the system are independent of the azimuthal
      quantum number l. First, by reformulating the N-photon absorption cross section
      of a single active electron, we prove that their assumptions reduce the network
      of optically allowed transition pathways into what we call the "Pascal triangle"
      consisting of (N + 1) (N + 2)/2 states only. Next, nonperturbative analytical and
      numerical solutions of the time-dependent Schrodinger equation for a simple model
      of two-photon excitation are presented not only in the low-intensity regime but
      also in the high-intensity regime. The results show that the determining factor
      of ellipticity-dependent multiphoton excitation probability is transition moment
      magnitudes and that the detailed energetic structure of the system also becomes
      important at high intensities. The experimentally observed flattening of the ion
      yields of xenon and C60 with increasing intensity can be explained without a
      saturation effect, which was previously deemed to be responsible for it. We also
      argue the applicability range of the cross section formula by Hertel et al. and
      the identity of the "doorway state" for ionization of C60.

PMID- 29055325
TI  - The intermolecular dimer potential for guanine.
AB  - The ab initio intermolecular potential of guanine has been developed with the
      help of a combination of symmetry-adapted perturbation theory and density
      functional theory (DFT). The resulting potential has been globally optimized to
      locate the guanine cluster structures up to tetramers. It has been found that the
      new potential is able to reproduce the known guanine cluster structures,
      especially the guanine quartet stabilized by Hoogsteen hydrogen bonds, in
      addition to new low-energy conformers. The performance of the potential was also
      compared with the AMBER force field as well as DFT-D and MP2 levels of theory.
      The model potential is in agreement with the ab initio methods and it shows a
      better performance compared to AMBER. Therefore, it can be further exploited in
      molecular dynamics or global optimizations to determine the structure and energy
      of much larger guanine clusters.

PMID- 29055326
TI  - Ab initio sampling of transition paths by conditioned Langevin dynamics.
AB  - We propose a novel stochastic method to generate Brownian paths conditioned to
      start at an initial point and end at a given final point during a fixed time tf
      under a given potential U(x). These paths are sampled with a probability given by
      the overdamped Langevin dynamics. We show that these paths can be exactly
      generated by a local stochastic partial differential equation. This equation
      cannot be solved in general but we present several approximations that are valid
      either in the low temperature regime or in the presence of barrier crossing. We
      show that this method warrants the generation of statistically independent
      transition paths. It is computationally very efficient. We illustrate the method
      first on two simple potentials, the two-dimensional Mueller potential and the
      Mexican hat potential, and then on the multi-dimensional problem of
      conformational transitions in proteins using the "Mixed Elastic Network Model" as
      a benchmark.

PMID- 29055327
TI  - Density functional theory formulation for fluid adsorption on correlated random
      surfaces.
AB  - We provide novel random surface density functional theory (RSDFT) formulation in
      the case of geometric heterogeneous surfaces of solid media which is essential
      for the description of thermodynamic properties of confined fluids. The major
      difference of our theoretical approach from the existing ones is a stochastic
      model of solid surfaces which takes into account the correlation properties of
      geometry. The main building blocks are effective fluid-solid potentials developed
      in the work of Khlyupin and Aslyamov [J. Stat. Phys. 167, 1519 (2017)] and
      geometry-based modification of the Helmholtz free energy for Lennard-Jones
      fluids. The efficiency of RSDFT is demonstrated in the calculation of argon and
      nitrogen low temperature adsorption on real heterogeneous surfaces (BP280 carbon
      black). These results are in good agreement with experimental data published in
      the literature. Also several models of corrugated materials are developed in the
      framework of RSDFT. Numerical analysis demonstrates a strong influence of surface
      roughness characteristics on adsorption isotherms. Thus the developed formalism
      provides a connection between a rigorous description of the stochastic surface
      and confined fluid thermodynamics.

PMID- 29055329
TI  - A wrinkling-based method for investigating glassy polymer film relaxation as a
      function of film thickness and temperature.
AB  - We investigate the relaxation dynamics of thin polymer films at temperatures
      below the bulk glass transition Tg by first compressing polystyrene films
      supported on a polydimethylsiloxane substrate to create wrinkling patterns and
      then observing the slow relaxation of the wrinkled films back to their final
      equilibrium flat state by small angle light scattering. As with recent relaxation
      measurements on thin glassy films reported by Fakhraai and co-workers, we find
      the relaxation time of our wrinkled films to be strongly dependent on film
      thickness below an onset thickness on the order of 100 nm. By varying the
      temperature between room temperature and Tg (~100  degrees C), we find that the
      relaxation time follows an Arrhenius-type temperature dependence to a good
      approximation at all film thicknesses investigated, where both the activation
      energy and the relaxation time pre-factor depend appreciably on film thickness.
      The wrinkling relaxation curves tend to cross at a common temperature somewhat
      below Tg, indicating an entropy-enthalpy compensation relation between the
      activation free energy parameters. This compensation effect has also been
      observed recently in simulated supported polymer films in the high temperature
      Arrhenius relaxation regime rather than the glassy state. In addition, we find
      that the film stress relaxation function, as well as the height of the wrinkle
      ridges, follows a stretched exponential time dependence and the short-time
      effective Young's modulus derived from our modeling decreases sigmoidally with
      increasing temperature-both characteristic features of glassy materials. The
      relatively facile nature of the wrinkling-based measurements in comparison to
      other film relaxation measurements makes our method attractive for practical
      materials development, as well as fundamental studies of glass formation.

PMID- 29055328
TI  - Peptide dimerization-dissociation rates from replica exchange molecular dynamics.
AB  - We show how accurate rates of formation and dissociation of peptide dimers can be
      calculated using direct transition counting (DTC) from replica-exchange molecular
      dynamics (REMD) simulations. First, continuous trajectories corresponding to
      system replicas evolving at different temperatures are used to assign
      conformational states. Second, we analyze the entire REMD data to calculate the
      corresponding rates at each temperature directly from the number of transition
      counts. Finally, we compare the kinetics extracted directly, using the DTC
      method, with indirect estimations based on trajectory likelihood maximization
      using short-time propagators and on decay rates of state autocorrelation
      functions. For systems with relatively low-dimensional intrinsic conformational
      dynamics, the DTC method is simple to implement and leads to accurate temperature
      dependent rates. We apply the DTC rate-extraction method to all-atom REMD
      simulations of dimerization of amyloid-forming NNQQ tetrapetides in explicit
      water. In an assessment of the REMD sampling efficiency with respect to standard
      MD, we find a gain of more than a factor of two at the lowest temperature.

PMID- 29055330
TI  - Algorithmic developments of the kinetic activation-relaxation technique:
      Accessing long-time kinetics of larger and more complex systems.
AB  - In spite of the considerable computer speed increase of the last decades, long
      time atomic simulations remain a challenge and most molecular dynamical
      simulations are limited to 1 MUs at the very best in condensed matter and
      materials science. There is a need, therefore, for accelerated methods that can
      bridge the gap between the full dynamical description of molecular dynamics and
      experimentally relevant time scales. This is the goal of the kinetic Activation
      Relaxation Technique (k-ART), an off-lattice kinetic Monte-Carlo method with on
      the-fly catalog building capabilities based on the topological tool NAUTY and the
      open-ended search method Activation-Relaxation Technique (ART nouveau) that has
      been applied with success to the study of long-time kinetics of complex
      materials, including grain boundaries, alloys, and amorphous materials. We
      present a number of recent algorithmic additions, including the use of local
      force calculation, two-level parallelization, improved topological description,
      and biased sampling and show how they perform on two applications linked to
      defect diffusion and relaxation after ion bombardement in Si.

PMID- 29055331
TI  - Automated placement of interfaces in conformational kinetics calculations using
      machine learning.
AB  - Several recent implementations of algorithms for sampling reaction pathways
      employ a strategy for placing interfaces or milestones across the reaction
      coordinate manifold. Interfaces can be introduced such that the full feature
      space describing the dynamics of a macromolecule is divided into Voronoi (or
      other) cells, and the global kinetics of the molecular motions can be calculated
      from the set of fluxes through the interfaces between the cells. Although some
      methods of this type are exact for an arbitrary set of cells, in practice, the
      calculations will converge fastest when the interfaces are placed in regions
      where they can best capture transitions between configurations corresponding to
      local minima. The aim of this paper is to introduce a fully automated machine
      learning algorithm for defining a set of cells for use in kinetic sampling
      methodologies based on subdividing the dynamical feature space; the algorithm
      requires no intuition about the system or input from the user and scales to high
      dimensional systems.

PMID- 29055332
TI  - Structural correlation in water probed by hyper-Rayleigh scattering.
AB  - Second-harmonic or hyper-Rayleigh scattering (HRS) is sensitive to molecular
      interactions and correlations, and there is a large coherent HRS contribution for
      water. This work shows that the distinctive angle and polarization dependence
      observed for HRS from water is due to the long-range orientation correlation of
      the molecules. The results of HRS experiments for water are analyzed in
      combination with a molecular dynamics simulation to determine the molecular
      hyperpolarizability and the short-range and long-range orientation correlation
      functions for the molecules. At long range, the longitudinal and transverse
      dipole-dipole orientation correlation functions are BL(r) = -2BT(r) = a3/r3 with
      a = 0.166 nm. Molecular correlation at distances r > 100 nm must be included to
      account for the HRS observations.

PMID- 29055333
TI  - Anisotropic kinetic energy release and gyroscopic behavior of CO2 super rotors
      from an optical centrifuge.
AB  - An optical centrifuge is used to generate an ensemble of CO2 super rotors with
      oriented angular momentum. The collision dynamics and energy transfer behavior of
      the super rotor molecules are investigated using high-resolution transient IR
      absorption spectroscopy. New multipass IR detection provides improved sensitivity
      to perform polarization-dependent transient studies for rotational states with 76
      <= J <= 100. Polarization-dependent measurements show that the collision-induced
      kinetic energy release is spatially anisotropic and results from both near
      resonant energy transfer between super rotor molecules and non-resonant energy
      transfer between super rotors and thermal molecules. J-dependent studies show
      that the extent and duration of the orientational anisotropy increase with
      rotational angular momentum. The super rotors exhibit behavior akin to molecular
      gyroscopes, wherein molecules with larger amounts of angular momentum are less
      likely to change their angular momentum orientation through collisions.

PMID- 29055334
TI  - Calculations of nuclear magnetic shielding constants based on the exact two
      component relativistic method.
AB  - From the matrix representation of the modified Dirac equation based on the
      restricted magnetically balanced gauge-including atomic orbital (RMB-GIAO) basis,
      previously one of the authors (Yoshizawa) and co-workers derived the two
      component normalized elimination of the small component (2c-NESC) formulas for 2c
      relativistic calculations of nuclear magnetic resonance (NMR) shielding tensors.
      In the present study, at the Hartree-Fock (HF) level, we numerically confirm that
      for several molecules the RMB-GIAO-based 2c-NESC method provides gauge-origin
      independent NMR shielding values. Moreover, we investigate the accuracy of the 2c
      NESC method by comparison with the 4c relativistic NMR calculations at the HF
      level. For noble gas dimers and Hg compounds, it is shown that the 2c-NESC method
      reproduces the 4c relativistic NMR shielding constants within errors of 0.12%
      0.31% of the 4c relativistic values and yields chemical shifts sufficiently close
      to the 4c relativistic results. Also, we discuss the basis set convergence of NMR
      shielding constants calculated with the 2c-NESC and 4c relativistic methods.

PMID- 29055335
TI  - Transition path sampling of rare events by shooting from the top.
AB  - Transition path sampling is a powerful tool in the study of rare events. Shooting
      trial trajectories from configurations along existing transition paths proved
      particularly efficient in the sampling of reactive trajectories. However, most
      shooting attempts tend not to result in transition paths, in particular in cases
      where the transition dynamics has diffusive character. To overcome the resulting
      efficiency problem, we developed an algorithm for "shooting from the top." We
      first define a shooting range through which all paths have to pass and then shoot
      off trial trajectories only from within this range. For a well chosen shooting
      range, nearly every shot is successful, resulting in an accepted transition path.
      To deal with multiple mechanisms, weighted shooting ranges can be used. To cope
      with the problem of unsuitably placed shooting ranges, we developed an algorithm
      that iteratively improves the location of the shooting range. The transition path
      sampling procedure is illustrated for models of diffusive and Langevin dynamics.
      The method should be particularly useful in cases where the transition paths are
      long so that only relatively few shots are possible, yet reasonable order
      parameters are known.

PMID- 29055336
TI  - Potential energy surfaces for O + O2 collisions.
AB  - We present global potential energy surfaces for nine adiabatic electronic states
      of O3, namely, 1 1A', 2 1A', 1 1A", 1 3A', 2 3A', 1 3A", 1 5A', 2 5A', and 1 5A".
      These are the states of O3 that are accessed in electronically adiabatic
      collisions of a ground-state triplet O2 molecule with a ground-state triplet O
      atom. The surfaces are based on XMS-CASPT2 electronic structure calculations with
      dynamically scaled external correlation. The active space has 12 active electrons
      distributed in the nine 2p orbitals. The adiabatic surfaces are fitted to
      analytic functions using a many-body expansion where the pairwise additive term
      is fitted to an accurate diatomic potential including a damped dispersion term,
      and the many-body part, without disconnected terms, is fitted with
      permutationally invariant polynomials in mixed exponential-Gaussians to the
      electronic structure data points. The selection and weighting of points for the
      fits are designed to produce surfaces suitable for describing energy transfer and
      dissociation in high-energy collisions.

PMID- 29055337
TI  - Nature of the guest-host interactions for dibromine in the T, P, and H clathrate
      cages.
AB  - The guest-host intermolecular potentials for the ground states of Br2 in the
      tetrakaidecahedral (T), pentakaidecahedral (P), and hexakaidecahedral clathrate
      (H) cages have been calculated using ab initio local correlation methods.
      Applying the local correlation energy partitioning analysis together with first
      order symmetry adapted perturbation theory, we obtain a detailed understanding of
      the nature of the interactions. In particular, the debated question concerning
      the possible presence of halogen bonding (XB) is carefully analyzed. In the case
      of the T cage, given its smaller size, the Br-O distance is too short leading to
      a larger exchange-repulsion for XB orientations which therefore do not represent
      minima. For the other two cages, the Br-O distance is too large leading to little
      orbital overlap effects and thus weaker donor-acceptor interactions; however,
      these orientations coincide with the global minima.

PMID- 29055338
TI  - Examining transition metal hydrosulfides: The pure rotational spectrum of ZnSH
      (X2A').
AB  - The pure rotational spectrum of the ZnSH (X2A') radical has been measured using
      millimeter-wave direct absorption and Fourier transform microwave (FTMW) methods
      across the frequency range 18-468 GHz. This work is the first gas-phase detection
      of ZnSH by any spectroscopic technique. Spectra of the 66ZnSH, 68ZnSH, and 64ZnSD
      isotopologues were also recorded. In the mm-wave study, ZnSH was synthesized in a
      DC discharge by the reaction of zinc vapor, generated by a Broida-type oven, with
      H2S; for FTMW measurements, the radical was made in a supersonic jet expansion by
      the same reactants but utilizing a discharge-assisted laser ablation source.
      Between 7 and 9 rotational transitions were recorded for each isotopologue.
      Asymmetry components with Ka = 0 through 6 were typically measured in the mm-wave
      region, each split into spin-rotation doublets. In the FTMW spectra, hyperfine
      interactions were also resolved, arising from the hydrogen or deuterium nuclear
      spins of I = 1/2 or I = 1, respectively. The data were analyzed using an
      asymmetric top Hamiltonian, and rotational, spin-rotation, and magnetic hyperfine
      parameters were determined for ZnSH, as well as the quadrupole coupling constant
      for ZnSD. The observed spectra clearly indicate that ZnSH has a bent geometry.
      The rm(1) structure was determined to be rZn-S = 2.213(5) A, rS-H = 1.351(3) A,
      and thetaZn-S-H = 90.6(1) degrees , suggesting that the bonding occurs primarily
      through sulfur p orbitals, analogous to H2S. The hyperfine constants indicate
      that the unpaired electron in ZnSH primarily resides on the zinc nucleus.

PMID- 29055339
TI  - High-level theoretical study of the reaction between hydroxyl and ammonia:
      Accurate rate constants from 200 to 2500 K.
AB  - Hydrogen abstraction from NH3 by OH to produce H2O and NH2-an important reaction
      in combustion of NH3 fuel-was studied with a theoretical approach that combines
      high level quantum chemistry and advanced chemical kinetics methods. Thermal rate
      constants calculated from first principles agree well (within 5%-20%) with
      available experimental data over a temperature range that extends from 200 to
      2500 K. Quantum mechanical tunneling effects were found to be important; they
      lead to a decided curvature and non-Arrhenius behavior for the rate constant.

PMID- 29055340
TI  - Structural determination and population transfer of 4-nitroanisole by broadband
      microwave spectroscopy and tailored microwave pulses.
AB  - The rotational spectrum of 4-nitroanisole was recorded via chirped-pulse Fourier
      transform microwave spectroscopy in the frequency range of 2-8 GHz. The spectra
      of the parent molecule and all of its 13C-, 15N-, and 18O-monosubstituted species
      in their natural abundance were assigned, and the molecular structure was
      determined using Kraitchman's equations as well as a least-square fitting
      approach. 4-nitroanisole has a large dipole moment of 6.15 D along the inertial a
      axis and a smaller dipole moment of 0.78 D along the b-axis. The large dipole
      moment component makes this molecule a potential candidate for deceleration
      experiments using static electric fields or electromagnetic radiation. Using
      tailored microwave pulses, we investigate the possibility of transferring
      population between the rotational states of 4-nitroanisole. Such a technique
      could be applied to selectively increase the population for specific rotational
      states of interest, which are then accessible for further, more advanced
      experiments, such as deceleration.

PMID- 29055341
TI  - Cluster analysis of accelerated molecular dynamics simulations: A case study of
      the decahedron to icosahedron transition in Pt nanoparticles.
AB  - Modern molecular-dynamics-based techniques are extremely powerful to investigate
      the dynamical evolution of materials. With the increase in sophistication of the
      simulation techniques and the ubiquity of massively parallel computing platforms,
      atomistic simulations now generate very large amounts of data, which have to be
      carefully analyzed in order to reveal key features of the underlying
      trajectories, including the nature and characteristics of the relevant reaction
      pathways. We show that clustering algorithms, such as the Perron Cluster Cluster
      Analysis, can provide reduced representations that greatly facilitate the
      interpretation of complex trajectories. To illustrate this point, clustering
      tools are used to identify the key kinetic steps in complex accelerated molecular
      dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This
      analysis provides an easily interpretable coarse representation of the reaction
      pathways in terms of a handful of clusters, in contrast to the raw trajectory
      that contains thousands of unique states and tens of thousands of transitions.

PMID- 29055342
TI  - Cluster decomposition of full configuration interaction wave functions: A tool
      for chemical interpretation of systems with strong correlation.
AB  - Approximate full configuration interaction (FCI) calculations have recently
      become tractable for systems of unforeseen size, thanks to stochastic and
      adaptive approximations to the exponentially scaling FCI problem. The result of
      an FCI calculation is a weighted set of electronic configurations, which can also
      be expressed in terms of excitations from a reference configuration. The
      excitation amplitudes contain information on the complexity of the electronic
      wave function, but this information is contaminated by contributions from
      disconnected excitations, i.e., those excitations that are just products of
      independent lower-level excitations. The unwanted contributions can be removed
      via a cluster decomposition procedure, making it possible to examine the
      importance of connected excitations in complicated multireference molecules which
      are outside the reach of conventional algorithms. We present an implementation of
      the cluster decomposition analysis and apply it to both true FCI wave functions,
      as well as wave functions generated from the adaptive sampling CI algorithm. The
      cluster decomposition is useful for interpreting calculations in chemical
      studies, as a diagnostic for the convergence of various excitation manifolds, as
      well as as a guidepost for polynomially scaling electronic structure models.
      Applications are presented for (i) the double dissociation of water, (ii) the
      carbon dimer, (iii) the pi space of polyacenes, and (iv) the chromium dimer.
      While the cluster amplitudes exhibit rapid decay with an increasing rank for the
      first three systems, even connected octuple excitations still appear important in
      Cr2, suggesting that spin-restricted single-reference coupled-cluster approaches
      may not be tractable for some problems in transition metal chemistry.

PMID- 29055343
TI  - Pathways for diffusion in the potential energy landscape of the network glass
      former SiO2.
AB  - We study the dynamical behaviour of a computer model for viscous silica, the
      archetypal strong glass former, and compare its diffusion mechanism with earlier
      studies of a fragile binary Lennard-Jones liquid. Three different methods of
      analysis are employed. First, the temperature and time scale dependence of the
      diffusion constant is analysed. Negative correlation of particle displacements
      influences transport properties in silica as well as in fragile liquids. We
      suggest that the difference between Arrhenius and super-Arrhenius diffusive
      behaviour results from competition between the correlation time scale and the
      caging time scale. Second, we analyse the dynamics using a geometrical definition
      of cage-breaking transitions that was proposed previously for fragile glass
      formers. We find that this definition accurately captures the bond rearrangement
      mechanisms that control transport in open network liquids, and reproduces the
      diffusion constants accurately at low temperatures. As the same method is
      applicable to both strong and fragile glass formers, we can compare correlation
      time scales in these two types of systems. We compare the time spent in chains of
      correlated cage breaks with the characteristic caging time and find that
      correlations in the fragile binary Lennard-Jones system persist for an order of
      magnitude longer than those in the strong silica system. We investigate the
      origin of the correlation behaviour by sampling the potential energy landscape
      for silica and comparing it with the binary Lennard-Jones model. We find no
      qualitative difference between the landscapes, but several metrics suggest that
      the landscape of the fragile liquid is rougher and more frustrated. Metabasins in
      silica are smaller than those in binary Lennard-Jones and contain fewer high
      barrier processes. This difference probably leads to the observed separation of
      correlation and caging time scales.

PMID- 29055345
TI  - Active sieving across driven nanopores for tunable selectivity.
AB  - Molecular separation traditionally relies on sieving processes across passive
      nanoporous membranes. Here we explore theoretically the concept of non
      equilibrium active sieving. We investigate a simple model for an active noisy
      nanopore, where gating-in terms of size or charge-is externally driven at a
      tunable frequency. Our analytical and numerical results unveil a rich sieving
      diagram in terms of the forced gating frequency. Unexpectedly, the separation
      ability is strongly increased as compared to its passive (zero frequency)
      counterpart. It also points to the possibility of tuning dynamically the osmotic
      pressure. Active separation outperforms passive sieving and represents a
      promising avenue for advanced filtration.

PMID- 29055344
TI  - A new class of enhanced kinetic sampling methods for building Markov state
      models.
AB  - Markov state models (MSMs) and other related kinetic network models are
      frequently used to study the long-timescale dynamical behavior of biomolecular
      and materials systems. MSMs are often constructed bottom-up using brute-force
      molecular dynamics (MD) simulations when the model contains a large number of
      states and kinetic pathways that are not known a priori. However, the resulting
      network generally encompasses only parts of the configurational space, and
      regardless of any additional MD performed, several states and pathways will still
      remain missing. This implies that the duration for which the MSM can faithfully
      capture the true dynamics, which we term as the validity time for the MSM, is
      always finite and unfortunately much shorter than the MD time invested to
      construct the model. A general framework that relates the kinetic uncertainty in
      the model to the validity time, missing states and pathways, network topology,
      and statistical sampling is presented. Performing additional calculations for
      frequently-sampled states/pathways may not alter the MSM validity time. A new
      class of enhanced kinetic sampling techniques is introduced that aims at
      targeting rare states/pathways that contribute most to the uncertainty so that
      the validity time is boosted in an effective manner. Examples including
      straightforward 1D energy landscapes, lattice models, and biomolecular systems
      are provided to illustrate the application of the method. Developments presented
      here will be of interest to the kinetic Monte Carlo community as well.

PMID- 29055346
TI  - Multifunctional energy landscape for a DNA G-quadruplex: An evolved molecular
      switch.
AB  - We explore the energy landscape for a four-fold telomere repeat, obtaining
      interconversion pathways between six experimentally characterised G-quadruplex
      topologies. The results reveal a multi-funnel system, with a variety of
      intermediate configurations and misfolded states. This organisation is identified
      with the intrinsically multi-functional nature of the system, suggesting a new
      paradigm for the classification of such biomolecules and clarifying issues
      regarding apparently conflicting experimental results.

PMID- 29055347
TI  - Interplay of fast and slow dynamics in rare transition pathways: The disk-to-slab
      transition in the 2d Ising model.
AB  - Rare transitions between long-lived stable states are often analyzed in terms of
      free energy landscapes computed as functions of a few collective variables. Here,
      using transitions between geometric phases as example, we demonstrate that the
      effective dynamics of a system along these variables are an essential ingredient
      in the description of rare events and that the static perspective provided by the
      free energy alone may be misleading. In particular, we investigate the disk-to
      slab transition in the two-dimensional Ising model starting with a calculation of
      a two-dimensional free energy landscape and the distribution of committor
      probabilities. While at first sight it appears that the committor is incompatible
      with the free energy, they can be reconciled with each other using a two
      dimensional Smoluchowski equation that combines the free energy landscape with
      state dependent diffusion coefficients. These results illustrate that dynamical
      information is not only required to calculate rate constants but that neglecting
      dynamics may also lead to an inaccurate understanding of the mechanism of a given
      process.

PMID- 29055348
TI  - Size-dependent bandgap and particle size distribution of colloidal semiconductor
      nanocrystals.
AB  - A new analytical expression for the size-dependent bandgap of colloidal
      semiconductor nanocrystals is proposed within the framework of the finite-depth
      square-well effective mass approximation in order to provide a quantitative
      description of the quantum confinement effect. This allows one to convert optical
      spectroscopic data (photoluminescence spectrum and absorbance edge) into accurate
      estimates for the particle size distributions of colloidal systems even if the
      traditional effective mass model is expected to fail, which occurs typically for
      very small particles belonging to the so-called strong confinement limit. By
      applying the reported theoretical methodologies to CdTe nanocrystals synthesized
      through wet chemical routes, size distributions are inferred and compared
      directly to those obtained from atomic force microscopy and transmission electron
      microscopy. This analysis can be used as a complementary tool for the
      characterization of nanocrystal samples of many other systems such as the II-VI
      and III-V semiconductor materials.

PMID- 29055349
TI  - A finite state projection algorithm for the stationary solution of the chemical
      master equation.
AB  - The chemical master equation (CME) is frequently used in systems biology to
      quantify the effects of stochastic fluctuations that arise due to biomolecular
      species with low copy numbers. The CME is a system of ordinary differential
      equations that describes the evolution of probability density for each population
      vector in the state-space of the stochastic reaction dynamics. For many examples
      of interest, this state-space is infinite, making it difficult to obtain exact
      solutions of the CME. To deal with this problem, the Finite State Projection
      (FSP) algorithm was developed by Munsky and Khammash [J. Chem. Phys. 124(4),
      044104 (2006)], to provide approximate solutions to the CME by truncating the
      state-space. The FSP works well for finite time-periods but it cannot be used for
      estimating the stationary solutions of CMEs, which are often of interest in
      systems biology. The aim of this paper is to develop a version of FSP which we
      refer to as the stationary FSP (sFSP) that allows one to obtain accurate
      approximations of the stationary solutions of a CME by solving a finite linear
      algebraic system that yields the stationary distribution of a continuous-time
      Markov chain over the truncated state-space. We derive bounds for the
      approximation error incurred by sFSP and we establish that under certain
      stability conditions, these errors can be made arbitrarily small by appropriately
      expanding the truncated state-space. We provide several examples to illustrate
      our sFSP method and demonstrate its efficiency in estimating the stationary
      distributions. In particular, we show that using a quantized tensor-train
      implementation of our sFSP method, problems admitting more than 100 * 106 states
      can be efficiently solved.

PMID- 29055351
TI  - Palliative Nephrology: Time for New Insights.

PMID- 29055350
TI  - Berberine alleviates oxidative stress in rats with osteoporosis through receptor
      activator of NF-kB/receptor activator of NF-kB ligand/osteoprotegerin
      (RANK/RANKL/OPG) pathway.
AB  - Previous studies suggested that oxidative stress is related to the onset and
      development of osteoporosis. Moreover, it was demonstrated that berberine has a
      protective effect against oxidative stress-induced injuries. In this study, we
      aimed to investigate the effect and mechanism of action of berberine on rats with
      induced osteoporosis. Sixty 8-week-old female Wistar rats were randomly divided
      into the following 6 groups: control saline-treated, osteoporosis saline-treated,
      3 osteoporosis berberine-treated groups (Ber 5, 10, and 20 mg/kg/body weight,
      respectively), and osteoporosis alendronate-treated (ALD) group. Osteoporosis was
      induced by bilateral ovariectomy. All treatments were performed for 8 weeks. The
      bone mineral density (BMD), serum alkaline phosphatase (ALP), osteocalcin,
      calcium, phosphorus, superoxide dismutase (SOD), methylenedioxyamphetamine (MDA),
      and glutathione peroxidase (GSH-Px) level was determined in the rat femur tissue.
      The gene and protein expression of osteoprotegerin (OPG) and receptor activator
      of nuclear factor kappa-B ligand (RANKL) was analyzed by quantitative reverse
      transcription PCR and Western blot, respectively. The BMD, SOD and GSH?Px levels,
      and the expression of OPG were significantly lower in osteoporosis compared to
      control group (all p < 0.05). The serum levels of osteocalcin, ALP, and MDA, and
      the expression of RANKL were significantly higher in osteoporosis compared to
      control group (all p < 0.05). Berberine, especially the high doses of berberine,
      effectively increased SOD, GSH?Px, and OPG levels as well as decreased serum
      osteocalcin, ALP, MDA and RANKL levels in berberine-treated osteoporosis groups
      (all p < 0.05). To conclude, oxidative stress may promote the development of
      osteoporosis in rats through the RANK/RANKL/OPG pathway. The antioxidative effect
      of berberine reduces the development of osteoporosis in rats to some extent.

PMID- 29055352
TI  - Deprescribing in CKD: The Proof Is in the Process.

PMID- 29055353
TI  - Acute Kidney Injury, Hypercalcemia, and Osteolytic Lesions: A Familiar Triad With
      a Rare Cause Complicated by Posterior Reversible Encephalopathy Syndrome.

PMID- 29055354
TI  - AJKD Atlas of Renal Pathology: Fibronectin Glomerulopathy.

PMID- 29055355
TI  - Myths and Realities Surrounding the Mysterious Caterpillar Fungus.
AB  - The caterpillar fungus Ophiocordyceps sinensis is a medicinal mushroom
      increasingly used as a dietary supplement for various health conditions,
      including fatigue, chronic inflammation, and male impotence. Here, we propose
      strategies to address the existing challenges related to the study and commercial
      production of this mysterious fungus.

PMID- 29055356
TI  - Dry Eye Disease: Let's Start Thinking Outside of the Artificial Tear Box.

PMID- 29055357
TI  - Inflammation in Dry Eye Disease: How Do We Break the Cycle?
AB  - This article reviews the literature and summarizes the role of inflammation in
      dry eye disease. A PubMed search was performed using the keywords inflammatory
      cycle and dry eye. All searches were limited to articles published in or
      translated into the English language, dating from 1973 through March 2017. There
      were no restrictions on the study design. Advances in understanding the
      pathogenesis of dry eye disease has revealed that inflammation is a core driver:
      the so-called "vicious circle" of inflammation. Researchers continue to analyze
      the precise mechanisms by which inflammation occurs. This has led to therapeutic
      options to break the cycle. Continued animal and human studies reveal other
      potential sites for treatment in this complex host of disorders.

PMID- 29055358
TI  - Meibomian Gland Disease: The Role of Gland Dysfunction in Dry Eye Disease.
AB  - TOPIC: To discuss the pathology, causes, and ocular surface impact of meibomian
      gland disease (MGD), as well as its relationship to dry eye. CLINICAL RELEVANCE:
      MGD is a common disorder with various contributing mechanisms and clinical
      manifestations. Understanding MGD pathophysiology and its relationship to dry eye
      is important in order to optimize diagnosis and treatment algorithms. METHODS: A
      review of current literature was performed to discern MGD in terms of
      pathophysiology, risk factors, and ocular surface impact, and the relationship to
      dry eye. RESULTS: Meibomian gland obstruction and meibocyte depletion are
      important components of MGD. Many pathologies can disrupt function of meibomian
      glands, ranging from congenital to acquired causes. Once gland disruption occurs,
      the quality and quantity of meibum is altered, with a negative impact on the
      ocular surface. Increased tear evaporation, tear hyperosmolarity, increased
      ocular surface staining, increased inflammation, symptomatic irritation of the
      eyelid and globes, as well as decreased visual acuity have all been observed.
      CONCLUSION: MGD leads to changes in meibum quality and quantity that can cause
      evaporative dry eye and ocular surface disruption, leading to dry eye symptoms in
      some individuals.

PMID- 29055359
TI  - Update in Current Diagnostics and Therapeutics of Dry Eye Disease.
AB  - Dry eye disease (DED) represents a heterogeneous group of conditions with tear
      film insufficiency and signs and/or symptoms of ocular surface irritation. The
      clinical manifestations of DED can be highly variable; hence the diagnosis is
      often based on a combination of symptoms, signs, and clinical tests, given that
      any one of these alone would miss a significant number of patients. Similarly,
      the treatment must often be tailored to each patient by targeting the specific
      mechanisms involved in his or her disease. The purpose of this review is to
      summarize recent advances that have allowed us to better recognize, categorize,
      and treat patients with DED. The most notable new diagnostic tests in DED are
      tear film osmolarity, inflammatory biomarkers, and meibomian gland imaging.
      Therapeutically, anti-inflammatory therapy, meibomian gland heating and
      expression, and scleral contact lenses are some of the latest options available
      for treating DED.

PMID- 29055362
TI  - The American Academy of Ophthalmology's IRIS(r) Registry (Intelligent Research in
      Sight Clinical Data): A Look Back and a Look to the Future.

PMID- 29055360
TI  - Neuropathic Corneal Pain: Approaches for Management.
AB  - Neuropathic pain is caused by a primary lesion or dysfunction of the nervous
      system and can occur in the cornea. However, neuropathic corneal pain (NCP) is
      currently an ill-defined disease. Patients with NCP are extremely challenging to
      manage, and evidence-based clinical recommendations for the management of
      patients with NCP are scarce. The objectives of this review are to provide
      guidelines for diagnosis and treatment of patients with NCP and to summarize
      current evidence-based literature in this area. We performed a systematic
      literature search of all relevant publications between 1966 and 2017. Treatment
      recommendations are, in part, based on methodologically sound randomized
      controlled trials (RCTs), demonstrating superiority to placebo or relevant
      control treatments, and on the consistency of evidence, degree of efficacy, and
      safety. In addition, the recommendations include our own extensive experience in
      the management of these patients over the past decade. A comprehensive algorithm,
      based on clinical evaluation and complementary tests, is presented for diagnosis
      and subcategorization of patients with NCP. Recommended first-line topical
      treatments include neuroregenerative and anti-inflammatory agents, and first-line
      systemic pharmacotherapy includes tricyclic antidepressants and an
      anticonvulsant. Second-line oral treatments recommended include an opioid
      antagonist and opiate analgesics. Complementary and alternative treatments, such
      as cardiovascular exercise, acupuncture, omega-3 fatty acid supplementation, and
      gluten-free diet, may have additional benefits, as do potential noninvasive and
      invasive procedures in recalcitrant cases. Medication selection should be
      tailored on an individual basis, considering side effects, comorbidities, and
      levels of peripheral and centralized pain. Nevertheless, there is an urgent need
      for long-term studies and RCTs assessing the efficacy of treatments for NCP.

PMID- 29055363
TI  - Something Old (Trabeculectomy), Something New (Ab Interno Gelatin Microstent):
      Finally, a Marriage of Innovation and Outcome Data (without Concurrent Cataract
      Surgery)!

PMID- 29055364
TI  - The Promise of Optical Coherence Tomography Angiography in Glaucoma.

PMID- 29055365
TI  - Rigid Gas Permeable Lens Intraocular Foreign Body following Blunt Trauma.

PMID- 29055366
TI  - Descemetorhexis Without Graft Placement: Transplant of Descemet-Free Fragments.

PMID- 29055367
TI  - Favre Racauchot Syndrome Involving the Eyelids.

PMID- 29055361
TI  - The Pathophysiology of Dry Eye Disease: What We Know and Future Directions for
      Research.
AB  - Clinical and laboratory studies performed over the past few decades have
      discovered that dry eye is a chronic inflammatory disease that can be initiated
      by numerous extrinsic or intrinsic factors that promote an unstable and
      hyperosmolar tear film. These changes in tear composition, in some cases combined
      with systemic factors, lead to an inflammatory cycle that causes ocular surface
      epithelial disease and neural stimulation. Acute desiccation activates stress
      signaling pathways in the ocular surface epithelium and resident immune cells.
      This triggers production of innate inflammatory mediators that stimulate the
      production of matrix metalloprotease, inflammatory cell recruitment, and
      dendritic cell maturation. These mediators, combined with exposure of
      autoantigens, can lead to an adaptive T cell-mediated response. Cornea barrier
      disruption develops by protease-mediated lysis of epithelial tight junctions,
      leading to accelerated cell death; desquamation; an irregular, poorly lubricated
      cornea surface; and exposure and sensitization of epithelial nociceptors.
      Conjunctival goblet cell dysfunction and death are promoted by the T helper 1
      cytokine interferon gamma. These epithelial changes further destabilize the tear
      film, amplify inflammation, and create a vicious cycle. Cyclosporine and
      lifitegrast, the 2 US Food and Drug Administration-approved therapies, inhibit T
      cell activation and cytokine production. Although these therapies represent a
      major advance in dry eye therapy, they are not effective in improving discomfort
      and corneal epithelial disease in all patients. Preclinical studies have
      identified other potential therapeutic targets, biomarkers, and strategies to
      bolster endogenous immunoregulatory pathways. These discoveries will, it is
      hoped, lead to further advances in diagnostic classification and treatment.

PMID- 29055368
TI  - Simultaneous Traumatic Central Retinal Artery Occlusion and Optic Neuropathy.

PMID- 29055369
TI  - Infrared Pupillometry Using an Optical Coherence Tomography Scanner.

PMID- 29055370
TI  - Iris Flocculi and Type B Aortic Dissection.

PMID- 29055371
TI  - Re: Haripriya et al.: Long-term posterior capsule opacification reduction with
      square-edge polymethylmethacrylate intraocular lens: randomized controlled study
      (Ophthalmology. 2017;124:295-302).

PMID- 29055372
TI  - Reply.

PMID- 29055373
TI  - Re: Tooley et al.: Dacryocystorhinostomy for acquired nasolacrimal duct stenosis
      in the elderly (>=80 years of age) (Ophthalmology. 2017;124:263-267).

PMID- 29055374
TI  - Reply.

PMID- 29055375
TI  - Re: Duarte et al.: Lacrimal gland involvement in blepharophimosis-ptosis
      epicanthus inversus syndrome (Ophthalmology. 2017;124:399-406).

PMID- 29055376
TI  - Reply.

PMID- 29055377
TI  - Re: Liu et al.: Enhancement after small-incision lenticule extraction: incidence,
      risk factors, and outcomes (Ophthalmology. 2017;124:813-821).

PMID- 29055378
TI  - Reply.

PMID- 29055379
TI  - Biopsychosocial risk factors associated with chronic low back pain after lower
      limb amputation.
AB  - Low back pain is a common secondary health condition after lower limb amputation
      with important implications related to functional capabilities and overall
      quality of life. Despite the high prevalence of low back pain after lower limb
      amputation, the underlying etiologies of the disorder remain unknown. This
      hypothesis-driven communication provides evidence in support of using the
      multifactorial, biopsychosocial model of low back pain experience in the general
      population for identification of potential risk factors and rehabilitation
      targets for low back pain after lower limb amputation. Key findings that link
      biological, psychological, and social factors and the experience of low back pain
      in the general patient population with LBP are discussed while highlighting gaps
      in our current state of knowledge related to the association of these factor and
      presence of low back pain after lower limb amputation. Importantly, the aim of
      this communication was not to propose a new model, but rather to organize data
      originating from prior work into a coherent hypothesis-driven conceptual
      framework to better understand the need for multifaceted and multidisciplinary
      intervention approaches for effective treatment of low back pain after lower limb
      amputation.

PMID- 29055380
TI  - Piezoelectric material - A promising approach for bone and cartilage
      regeneration.
AB  - Bone and cartilage are major weight-bearing connective tissues in human and
      possesses utmost vulnerability for degeneration. The potential causes are
      mechanical trauma, cancer and disease condition like osteoarthritis and
      osteoporosis, etc. The regeneration/repair is a challenging, since their complex
      structures and activities. Current treatment options comprise of auto graft,
      allograft, artificial bone substituent, autologous chondrocyte implantation,
      mosaicplasty, marrow stimulation and tissue engineering. Were incompetent to
      overcome the problem like abandoned growth factor degradation, indistinct growth
      factor dose and lack of integrity and mechanical properties in regenerated
      tissues. Present, paper focuses on the novel hypothesis for regeneration of bone
      and cartilage by using piezoelectric smart property of scaffold material.

PMID- 29055381
TI  - Mimetic Theory and the evolutionary paradox of schizophrenia: The archetypal
      scapegoat hypothesis.
AB  - Schizophrenia poses an evolutionary paradox, being genetically mediated yet
      associated with reduced fecundity. Numerous hypotheses have attempted to address
      this, but few describe how the schizophrenic phenotype itself might constitute an
      evolutionary adaptation. This paper draws on Rene Girard's theory on human
      origins, which claims that humans evolved a tendency to mimic both the desires
      and the behaviours of each other (mimetic theory). This would have promoted
      social cohesion and co-operation, but at the cost of intra-group rivalry and
      conflict. The mimetic dynamic would have escalated such conflicts into reciprocal
      internecine violence, threatening the survival of the entire group. Girard
      theorised that the "scapegoat mechanism" emerged, by which means such violence
      was curtailed by the unanimity of "all against one", thus allowing the mimetic
      impulse to safely evolve further, making language and complex social behaviours
      possible. Whereas scapegoating may have emerged in the entire population, and any
      member of a community could be scapegoated if necessary, this paper proposes that
      the scapegoat mechanism would have worked better in groups containing members who
      exhibited traits, recognised by all others, which singled them out as victims.
      Schizophrenia may be a functional adaptation, similar in evolutionary terms to
      altruism, in that it may have increased inclusive fitness, by providing scapegoat
      victims, the choice of whom was likely to be agreed upon unanimously, even during
      internecine conflict, thus restoring order and protecting the group from self
      destruction. This evolutionary hypothesis, uses Girardian anthropology to combine
      the concept of the schizophrenic as religious shaman with that of the
      schizophrenic as scapegoat. It may help to reconcile divergent philosophical
      concepts of mental illness, and also help us to better understand, and thus
      counter, social exclusion and stigmatisation.

PMID- 29055382
TI  - Subdural effusion protects the aging brain from harmful ventriculomegaly.
AB  - The human brain loses its volume and its function during aging. The solid part of
      the brain within the intracranial space, the brain parenchyma, decreases in
      volume with age; while the cerebrospinal fluid (CSF) volume increases. With
      progressive loss of brain parenchymal volume (BPV), CSF may shift from cerebral
      ventricles to the subdural space, forming subdural effusion (SDE), whose role in
      the brain aging process remains unclear. We hypothesize that damages associated
      with ventriculomegaly can be lessened after formation of SDE. As the BPV
      decreases, the enlarged ventricular surface area causes dysfunction of its lining
      ependymal cells, followed by damages to the periventricular tissue. The
      periventricular nerve fibers are stretched by the enlarged ventricles. We
      hypothesize that after the formation of SDE, ventriculomegaly can be stopped or
      even reversed. By allowing the atrophic brain to reside in a smaller fraction of
      the intracranial volume, damages associated with ventriculomegaly can be
      alleviated. If our hypothesis is correct, physicians should continue to maintain
      a conservative approach for uncomplicated SDE. For focal or global brain
      parenchymal loss caused by various pathologies, intracranial spacers can be
      employed to simulate the effect of SDE to protect the brain. For treatment of
      idiopathic normal pressure hydrocephalus, aggressive ventricular size reduction
      should be pursued. Finally, the protective effects of SDE have its limits.
      Extremely enlarged subdural volume can cause acute or chronic subdural hematoma,
      further damaging the brain.

PMID- 29055383
TI  - Use of polymethylmethacrylate (PMMA) microspheres collagen to treat atrophic acne
      scars.
AB  - Acne scarring is a common and persistent sequela affecting many individuals
      worldwide, with significant physical and long-lasting psychological effects.
      Currently, the treatment options available for acne scars are mostly invasive and
      have several side effects. This paper explores the possibility of using
      polymethylmethacrylate (PMMA) collagen microspheres, a relatively underexplored
      technique hitherto, to treat common atrophic scars. PMMA-collagen is more
      popularly used in injectable wrinkle fillers. Preliminary research has shown that
      PMMA-collagen has a beneficial effect on atrophic scars while having the added
      advantage of being safe, tolerable and minimally invasive as well.

PMID- 29055384
TI  - The central nervous system pressure histogram in hydrocephalus and hydromyelia.
AB  - This work makes proposals on the relationship between intracranial pressure (ICP)
      and hydrocephalus that changes over time with the evolution of the disease. This
      includes the cerebrospinal fluid (CSF) filling mechanism that leads to an
      increase in mode pressure if excess fluid volume exacerbates the obstructive
      process. Elevation in mode occurs because pressure in the central nervous system
      (CNS) represents a state of reduced flow, rather than an abnormality of volume.
      Diseases that cause elevated mode pressure by means of a primary edema can lead
      to hydrocephalus if there is sufficient time and obstruction to flow for the
      filling mechanism to act. Hydrocephalus is driven primarily by labile pressure
      due to restricted compliance, it can expand skeletal compartments and deplete
      parenchyma volume as it advances. This hypothesis applies existing principles of
      water balance. It is part of a series of works that propose a spectrum of
      hydrocephalic disorders including developmental forms such as achondroplasia with
      other conditions such as functional trapped fourth ventricle, arachnoid cyst,
      syringomyelia and normal pressure hydrocephalus (NPH). Links between the
      conditions can be made by understanding the continuously variable pressure
      profile local to the cavity that is subject to filling. Fluid lesions of the
      brain or spine that arise from developmental malformations of the skull have a
      physiological component. Changes form part of the mechanisms that may compensate
      the disease process.

PMID- 29055385
TI  - Is quadriceps H-reflex excitability a risk factor for patellofemoral pain?
AB  - Patellofemoral pain (PFP) is one of the most common conditions in orthopedic
      practice while recent evidence has suggested that it may be a predisposing factor
      to patellofemoral osteoarthritis. In addition to biomechanical alterations
      associated with the pathomechanisms underlying PFP, the investigation of
      neurophysiological alterations has provided novel information in the
      understanding of the pathophysiology of PFP. For instance, women with PFP present
      lower amplitude of the vastus medialis (VM) H-reflexes compared to pain-free
      controls, which suggests that the excitability of spinal reflexes might be a
      promising tool for discriminating woman with PFP in clinical practice. However,
      the cross-sectional design of the current research does not inform whether the
      reduced excitability predisposes to or is the consequence of PFP. Therefore, two
      hypotheses can be raised: (1) the reduction in excitability of the alpha
      motoneurons is a risk factor for PFP; Or, (2) the reduction in H-reflex
      excitability is a consequence of PFP due to pain. If the former hypothesis is
      proven correct, it may help in the early identification of individuals with PFP.
      If the latter, it may help understand the reduced excitability as a consequence
      of the long-term pain, which may be interfering in the recovery of individuals
      with PFP in a long-term basis. In addition, exploring such hypotheses may have
      direct rehabilitative and prevention implications for PFP and its putative
      progression to knee osteoarthritis.

PMID- 29055386
TI  - Peritoneal dialysis: The unique features by compartmental delivery of renal
      replacement therapy.
AB  - Despite decades of research, the clinical efficacy of peritoneal dialysis (PD)
      remains enigmatic. We may wonder why the modality fail in some patients but
      perhaps the more proper question would be, why it works in so many? We know that
      the contribution of residual renal function (RRF), more so than in hemodialysis,
      is critically important to the well-being of many of the patients. Unique
      features of the modality include the relatively low volume of dialysate fluid
      needed to provide effective uremic control and the disproportionate tendency for
      both hypokalemia and hypoalbuminemia, when compared to hemodialysis. It is
      currently believed that most uremic toxins are generated on the interface of
      human and bacterial structures in the gastrointestinal tract, the intestinal
      biota. PD offers disproportionate removal of these toxins upon "first-pass",
      i.e., via PD fluid exchanges before reaching the systemic circulation beyond the
      gastrointestinal compartment. Studies examining the net removal gradient of
      protein-bound uremic toxins during PD are scarce, whereas RRF receives
      considerably more attention without effective interventions being developed to
      preserve it. We propose an alternative view on PD, emphasizing the modality's
      compartmental nature, both for its benefits and the limitations.

PMID- 29055387
TI  - The colon revisited or the key to wellness, health and disease.
AB  - The hypothesis being advanced in this paper is that there is a new medical
      paradigm emerging from the biomedical research carried out in this century,
      mainly due to the explosion of the so called "omics" and associated techniques.
      The main idea is that there is a common pathway from wellbeing and health to
      chronic disease ("chronopathy") and even to death, which comprises following
      steps: 1) unhealthy diet, sedentary life style and permanent exposition to
      xenobiotics and all kinds of noxious stimuli;->2) intestinal dysbiosis;->3)
      alteration of the intestinal mucus layer (especially that of the colon);->4)
      disruption of the endothelial tight junctions;->5) metabolic
      endotoxemia+bacterial translocation;->6) inflammation;->7) exacerbation of the
      enteric nervous system (ENS) and consequent maladaptation and malfunctioning of
      the colon;->8) epigenetic manifestations;->9) "chronopathy" and premature death.
      Therefore, in order to maintain a good health or to improve or even reverse
      chronic diseases in a person, the main outcome to look for is a homeostatic
      balance of the intestinal microbiota (eubiosis), most of which is located in the
      colon. Lynn Margulis was one of the main scientists to highlight the importance
      of the role played by bacteria not only in the origin of all biological species
      now present on earth, but also on their role in global homeostasis. Bacteria do
      not rely on other living beings for their existence, while the latter depend
      completely on the former. Humans are no exemption, and new evidence emerges each
      day about the pivotal role of intestinal microbiota in human health, disease and,
      in general, in its wellbeing. The following facts about intestinal microbiota are
      nowadays generally accepted: there are about 10 times more bacteria in the gut
      than human cells in every human being; the microbioma is about 100-150 times
      bigger that the human genome, and there is a clear link between intestinal
      microbiota and many of the most common chronic diseases, from obesity and
      diabetes to depression and Parkinson disease and different kinds of cancer. The
      main implication of this theory is that we should become a sort of microbiota
      farmers, that is, we ought to be more conscious of our intestinal microbiota,
      take care of it and monitor it permanently. Thus, as part of our good life habits
      (healthy eating, physical exercise), we should probably undergo periodic seasons
      of fasting and colon cleansing, as it was common in older times.

PMID- 29055388
TI  - How extreme dieting becomes compulsive: A novel hypothesis for the role of
      anxiety in the development and maintenance of anorexia nervosa.
AB  - The US National Institute of Mental Health's Research Domain Criteria (NIMH RDoC)
      advocates the study of features common to psychiatric conditions. This
      transdiagnostic approach has recently been adopted into the study of anorexia
      nervosa (AN), an illness that can be considered compulsive in nature. This has
      led to the development of an account of AN that identifies key roles for the
      heightened reinforcement of starvation, leading to its excessive repetition, and
      goal-directed system dysfunction. Considering models of illness in other
      compulsive disorders, we extend the existing account to explain the emergence of
      reinforcement and goal-directed system abnormalities in AN, proposing that
      anxiety is central to both processes. As such we emphasise the particular
      importance of the anxiolytic effects of starvation, over other reinforcing
      outcomes, in encouraging the continuation of starvation within a model that
      proposes a number of mechanisms by which anxiety operates in the development and
      maintenance of AN. We suggest the psychopathology of AN mediates the relationship
      between the anxiolytic effects of starvation and excessive repetition of
      starvation, and that compulsive starvation has reciprocal effects on its
      determinants. We thus account for the emergence of symptoms of AN other than
      compulsive starvation, and for the relationship between different features of the
      disorder. By extending and adapting an existing explanation of AN, we provide a
      richer aetiological model that invites new research questions and could inform
      novel approaches to prevention and treatment.

PMID- 29055389
TI  - Could lung cancer exosomes induce apoptosis of natural killer cells through the
      p75NTR-proNGF-sortilin axis?
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Tumor
      exosomes play an important role in the development of lung cancer. Previous
      studies indicated that tumor exosomes derived from lung cancer cells contained
      abundant sortilin. Sortilin is a member of the vacuolar protein sorting 10
      protein (VPS10P) family of receptors that act as co-receptors for p75NTR and play
      an independent role in cell death induced by proNGF. Recently, a study showed
      that proNGF could mediate the death of natural killer (NK) cells through binding
      to the p75NTR-sortilin complex. However, it has not been reported, to our
      knowledge, that lung cancer cells induce NK cell apoptosis through a p75NTR
      proNGF-sortilin mechanism. As a secreted protein, lung cancer cells may release
      some proNGF into the tumor microenvironment. We therefore hypothesized that lung
      cancer cells may promote the apoptosis of NK cells through releasing exosomal
      sortilin and proNGF. To test this hypothesis, experiments involving the
      production of exosomal sortilin and proNGF in lung cancer cells and the
      expression of p75NTR in NK cells are required based upon previously established
      experiments using fluorescent components. Such experiments may provide insight
      into the potential mechanism by which lung cancer cells promote apoptosis of NK
      cells through a p75NTR-proNGF-sortilin pathway.

PMID- 29055390
TI  - Mycoplasma infection followed by time-lapse microscopy.
AB  - Early detection of mycoplasma infection is crucial for saving precious often
      irreplaceable data from the tissues of patients. Mycoplasma infections cause
      diseases in the upper and lower respiratory tracts, urethritis in men resulting
      in painful dysuria, urgency and urethral discharge. Cough, fever, headache,
      urethritis may persist for several weeks and convalescence is slow. The symptoms
      of these diseases are aggravated by the detection of mycoplasma infections, that
      takes either a long time, besides being expensive or is specific and restricted
      to only a limited number of contaminant strains. Mycoplasmas are hard to detect
      visually but could be seen and followed by time-lapse microscopy. Our hypothesis
      is that one can detect mycoplasma infection irrespective of its origin and type
      of mycoplasma. Main lines of supporting evidence are provided by the time-lapse
      microscopy showing dynamic morphological alterations caused by mycoplasmas before
      changes in human cell cultures become visible. Morphometric measurements of
      mycoplasma infections revealed four subphases: i) detachment of infected cells,
      ii) aggregation, iii) biofilm formation and iv) shrinkage of infected cells. The
      applicability of time-lapse microscopy for the detection of mycoplasma infection
      was validated by a mycoplasma test Kit. Most important implications related to
      morphometric parameters include the observation of mycoplasma infected cultures
      for an extended period of time instead of applying static snap-shot microscopy. A
      reliable method is offered to estimate the time of mycoplasma exposure that
      elapsed during the cell growth. This microphotometric approach served a more
      economical detection of mycoplasma contamination at its early stage of cell
      growth and spread, irrespective of the origin of contaminated serum, without
      defining the type of mycoplasma.

PMID- 29055391
TI  - A quick overview to the early phase clinical trials of Simtuzumab(r): Are we
      loosing the most promising anti-fibrotic product?

PMID- 29055393
TI  - Tumor-associated immune aggregates in oral cancer: Their cellular composition and
      potential prognostic significance.
AB  - There is growing evidence supporting the importance of immune microenvironment in
      cancer development and progression, especially with the rapid development of
      immunotherapy. Presence of immune cell aggregates in solid tumors has been
      associated with clinical outcomes, but little is known about the immune
      microenvironment in oral squamous cell carcinoma (OSCC), which has high morbidity
      and mortality. Based on our preliminary observation, we hypothesize that there is
      the presence of tumor-associated immune aggregates (TaIAs) during oral cancer
      development. Adapting to the dynamic change of the composition of cellular
      membership and co-evolving with the tumor at invasion fronts, these TaIAs, either
      pro-inflammatory or immune suppressive, are associated with clinical
      consequences. With the unique access to a set of prospectively collected, highly
      annotated OSCC surgical samples and the use of multi-color immunostaining of key
      immune cells, the confirmation of our hypothesis may shed light of the underlying
      biology related to OSCC and the knowledge learned can potentially be used to
      identify prognostic markers, response predictive markers for immunotherapies, as
      well as novel therapeutic targets.

PMID- 29055392
TI  - Sleep apnea: An overlooked cause of lipotoxicity?
AB  - Obstructive sleep apnea (OSA) is a common sleep disorder associated with diabetes
      and cardiovascular disease. However, the mechanisms by which OSA causes
      cardiometabolic dysfunction are not fully elucidated. OSA increases plasma free
      fatty acids (FFA) during sleep, reflecting excessive adipose tissue lipolysis. In
      animal studies, intermittent hypoxia simulating OSA also increases FFA, and the
      increase is attenuated by beta-adrenergic blockade. In other contexts, excessive
      plasma FFA can lead to ectopic fat accumulation, insulin resistance, vascular
      dysfunction, and dyslipidemia. Herein, we propose that OSA is a cause of
      excessive adipose tissue lipolysis contributing towards systemic "lipotoxicity".
      Since visceral and upper-body obesity contributes to OSA pathogenesis, OSA
      induced lipolysis may further aggravate the consequences of this metabolically
      harmful state. If this hypothesis is correct, then OSA may represent a reversible
      risk factor for cardio-metabolic dysfunction, and this risk might be mitigated by
      preventing OSA-induced lipolysis during sleep.

PMID- 29055395
TI  - The neural signature of emotional memories in serial crimes.
AB  - Neural plasticity is the process whereby semantic information and emotional
      responses are stored in neural networks. It is hypothesized that the neural
      networks built over time to encode the sexual fantasies that motivate serial
      killers to act should display a unique, detectable activation pattern. The
      pathological neural watermark hypothesis posits that such networks comprise
      activation of brain sites that reflect four cognitive components:
      autobiographical memory, sexual arousal, aggression, and control over aggression.
      The neural sites performing these cognitive functions have been successfully
      identified by previous research. The key findings are reviewed to hypothesise the
      typical pattern of activity that serial killers should display. Through the
      integration of biological findings into one framework, the neural approach
      proposed in this paper is in stark contrast with the many theories accounting for
      serial killers that offer non-medical taxonomies. The pathological neural
      watermark hypothesis offers a new framework to understand and detect deviant
      individuals. The technical and legal issues are briefly discussed.

PMID- 29055394
TI  - Is damage to the pre-frontal cortex dormant until adolescence, or difficult to
      detect? Looking for keys that unlock executive functions in children in the wrong
      place.
AB  - A range of functions can be negatively affected by pre-frontal cortex (PFC)
      injury, but observed behavioural and social changes are commonly linked to post
      injury changes in executive function. Executive functioning is a complex
      neuropsychological construct which is further complicated by neuro-developmental
      processes when applied to children. There is a substantial and continuing
      evidence base that supports the view that early childhood pre-frontal cortex
      (PFC) injury results in hidden, dormant, or sleeping effects. In contrast, recent
      and rapidly accruing contemporary studies provide preliminary evidence that
      challenge the view that PFC associated impairments are completely 'hidden'.
      Studies that examine the various functions of the PFC and differentiate these to
      provide preliminary evidence to indicate earlier EF development than that which
      develops upon reaching adolescence, are reviewed here, together with research
      that identifies early predictors of later EF impairments. It remains that studies
      of PFC function and/or structural brain-changes are substantially complicated by
      issues related to definition regarding functions of the PFC, measurement of EF
      and other PFC-related functions that may be better understood as meta-processes.
      These issues are discussed in the concluding sections of this paper.

PMID- 29055396
TI  - Role of gut microbiota in idiopathic nephrotic syndrome in children.
AB  - Nephrotic syndrome characterized by heavy proteinuria and edema is the most
      common chronic kidney disease in children. It is classified into three
      categories, of which the idiopathic type accounts for the vast majority of cases.
      As indicated by the name, the etiology of idiopathic nephrotic syndrome remains
      unknown though it has been suggested that impaired T cell function is involved.
      Recently, evidence has mounted to suggest that dysfunction in regulatory T cells
      plays an important role in the development of allergic disease, a recognized
      comorbid condition for children with idiopathic nephrotic syndrome. It is known
      that regulatory T cells are mainly induced by short chain fatty acids produced by
      gut microbiota and that children with allergy are reported to have aberrant gut
      microbiota. On this basis, we hypothesize that an aberrant microbiota, i.e.,
      dysbiosis in the gut resulting in defective induction of regulatory T cells, is
      also involved in the etiology of idiopathic nephrotic syndrome in children. Our
      hypothesis can be directly tested by metagenome analysis using bacterial DNA
      extracted from the feces of patients with idiopathic nephrotic syndrome. Indirect
      evidence could be obtained by epidemiological survey, such as a comparative study
      of the environmental factors influencing the initial colonization of gut
      microbiota between patients with idiopathic nephrotic syndrome and age-matched
      healthy children. Factors that may disrupt this colonization include a cesarean
      delivery, formula feeding, excessive use of antibiotics, or the introduction of
      inappropriate solid foods containing a high amount of saturated fat. Based on
      this hypothesis, we suggest it would be clinically worthwhile to study whether
      administration of probiotics composed of commensal bacteria known to efficiently
      induce regulatory T cells in vitro could control the exacerbation or relapse of
      INS.

PMID- 29055397
TI  - Vitamin K deficit and elastolysis theory in pulmonary elasto-degenerative
      diseases.
AB  - Elastin is a unique protein providing deformability and resilience to dynamic
      tissues, such as arteries and lungs. It is an absolute basic requirement for
      circulation and respiration. Elastin can be degraded by elastases and has a high
      calcium affinity. Elastin calcification and elastin degradation are two
      pathological processes that impair elastin's functioning. Furthermore, elastin
      degradation can be associated to elastin calcification. Matrix Gla Protein (MGP)
      is probably the most potent natural inhibitor of elastin calcification and
      requires vitamin K for its activation. Measuring circulating levels of inactive
      MGP (dp-ucMGP) is a frequently used method to assess vitamin K status. Dp-ucMGP
      reflects the burden of vitamin K-dependent proteins that have not been activated
      by vitamin K and could therefore best be regarded as a biomarker of a vitamin K
      deficit. Dp-ucMGP levels decrease after vitamin K supplementation. Since the
      amino acids desmosine and isodesmosine (DES) are unique to crosslinked elastin
      fibers, systemic elastin degradation can be assessed with the plasma DES assay.
      Recently, we discovered a strong correlation between plasma dp-ucMGP and plasma
      DES levels in both patients with chronic obstructive pulmonary disease (COPD) and
      controls. The 'Vitamin K deficit and elastolysis theory' posits that elastin
      degradation causes a rise in the vitamin K deficit and implies that vitamin K
      supplementation could be preventing elastin degradation. If this hypothesis holds
      true and is universally found in every state and condition, it will have an
      unprecedented impact on the management of every single pulmonary disease
      characterized by accelerated elastin degradation, such as alpha-1 antitrypsin
      deficiency, bronchiectasis, COPD and cystic fibrosis. Theoretically, a plasma dp
      ucMGP concentration of zero would be associated with a near-complete standstill
      of elastin degradation and disease progression in patients with any of these
      debilitating conditions.

PMID- 29055398
TI  - Dapsone as a potential treatment option for Henoch-Schonlein Purpura (HSP).
AB  - Henoch-Schonlein Purpura (HSP, IgA vasculitis) is an immunoglobulin A (IgA)
      mediated disorder characterized by systemic vasculitis with variable
      presentation, frequently affecting the skin, mucous membrane, joints, kidneys,
      and rarely lungs and the central nervous system. Interestingly, enhanced
      production of interleukin-8 (IL-8) levels are found during active disease and
      increased levels have been reported in supernatants from human umbilical venous
      endothelial cells after stimulation with sera from patients affected by HSP.
      While corticosteroid therapy is currently the recommended treatment for HSP,
      dapsone, an anti-leprosy agent, has also recently been suggested to have
      therapeutic efficacy due to its ability to suppress IL-8. Moreover, in addition
      to IL-8 suppression, dapsone has been reported to exert various anti-inflammatory
      effects by inhibiting the generation of toxic free radicals, myeloperoxidase
      mediated halogenation that converts H2O2 to HOCl, leukocyte chemotaxis,
      production of tumor necrosis factor, and other anti-inflammatory molecules. This
      review aims to provide a solid hypothesis for the pathogenesis of vasculitis in
      HSP. Moreover, we highlight potential mechanistic actions of dapsone in hopes
      that dapsone may be considered as an alternative viable treatment for patients
      affected by HSP.

PMID- 29055399
TI  - New digital adherence devices could prevent millions of strokes from atrial
      fibrillation by the end of the next century.
AB  - The effectiveness and safety of a pharmacologic intervention is highly dependent
      on patient's capability to follow the recommended treatment regimen. Non
      adherence to pharmacologic treatments is associated with worsening conditions
      including hospitalization and death. This is a significant burden to healthcare
      systems on a global scale with non-adherence rates being as high (or higher) as
      50% in the first treatment year. The most common causes for non-adherence are
      forgetfulness, busy lifestyle or complexity and changes in therapeutic schedules.
      In conditions like atrial fibrillation (AFib) this leads to a drastic increase in
      event rates, e.g. strokes. Patients diagnosed with AFib are strongly recommended
      to receive anticoagulant treatments for stroke prevention. Treatments with
      Vitamin K antagonists or novel oral anticoagulants (NOACs) can dramatically lower
      the risk of ischemic strokes in the presence of AFib. Non-adherence can expose
      the patients to an increased stroke risk. This is especially true for NOACs, due
      to their short half-life. Patients have to take these medications once or twice
      daily for adequate stroke prevention, i.e., single non-use of the medication can
      already diminish or reset the anticoagulative effect. Adherence devices could
      help improve patient's compliance by reminder or feedback function. They have
      shown to be successful in a number of clinical trails. Especially, newer devices
      that make use of digital technologies show promising results but are not used
      broadly in clinical practice. Here we provide evidence for our hypothesis that
      newly available adherence devices might increase adherence rates and thereby
      reduce the number of strokes in patients with AFib.

PMID- 29055400
TI  - Whether 25mM of metformin is achievable in human gut from a therapeutic dose of
      metformin?

PMID- 29055402
TI  - Caesarean section scar causes myometrial hypertrophy with subsequent heavy
      menstrual flow and dysmenorrhoea.
AB  - In the recent years, maternity statistics world-wide show a continuous rise in
      the rate of Caesarean Section (CS) operation. Many CS deliveries are conducted
      despite having no clear obstetric indications. The CS scar is assumed to be
      related to many adverse clinical gynaecological symptoms such as intermenstrual
      bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain; however, the
      mechanism of this relation is not clear. Further, little is known about the
      effects of CS scar on uterine wall morphology, function or patho-physiology. We
      hypothesize that: (i) the CS scar causes myometrial hypertrophy (myohypertrophy)
      of the anterior uterine wall above the scar, and (ii) the scar-induced
      morphological changes in the uterine wall causes adverse clinical gynaecological
      symptoms such as intermenstrual bleeding, dysmenorrhoea, dyspareunia and chronic
      pelvic pain. This article discusses the hypothesis and its clinical implications,
      as well as presents supportive preliminary data and the emerging research to
      prove it.

PMID- 29055401
TI  - How Hepatitis B virus causes cirrhosis and liver cancer.
AB  - Hepatitis B virus is a major pathogen infecting the liver, causing high morbidity
      and mortality worldwide, particularly in developing countries. The mechanism
      underlying progression from infections of Hepatitis B virus to cirrhosis and
      liver cancer is not fully determined. Here we propose that the HBV X protein
      traps protons and Cl-, and induces the expression of collagen in the liver, which
      forms potent hydrogen bonds with trapped protons. The presence of collagen in the
      liver marks the progression to fibrosis. The X protein and collagen concertedly
      build up HCl locally, triggering disease advances to liver cancer in some
      patients with liver cirrhosis. The hypothesis can be tested in Hepatitis B
      primate model with the administration of calcium and weak acids to ascertain
      physiological changes and monitor tumorigenesis rate. The experiments will pave
      the way for better intervention of human infections with Hepatitis B virus.

PMID- 29055403
TI  - Ancient roots - Modern applications: Mindfulness as a novel intervention for
      cardiovascular disease.
AB  - Cardiovascular disease (CVD) has been associated with chronic psychological
      stress. Unremittent psychological stress causes dysregulation of the sympathetic
      nervous system (SNS) and hypothalamic-pituitaryadrenal (HPA) axis, which
      collectively promotes inflammation, atherosclerosis, and subsequent CVD risk.
      Stress reduction techniques, such as mindfulness meditation, have been shown to
      improve some markers of HPA and SNS function at rest and in response to acute
      stressors, suggesting that such techniques, over time, may be cardioprotective.
      Therefore, it may be hypothesized that eight weeks of daily mindfulness
      meditation, compared to a non-mindful relaxation control, may provide a novel
      strategy to buffer stress responses in healthy and at-risk populations, thereby
      lowering the risk of chronic psychological stress and the associated CVD risk as
      measured by arterial stiffness. The current paper outlines methodological
      considerations for testing this hypothesis, including appropriate acute
      stressors, and measurement of SNS, HPA axis and cardiovascular function. If the
      hypothesis is correct, mindfulness meditation would complement healthy lifestyle
      techniques such as exercise and diet to prevent CVD risk.

PMID- 29055404
TI  - Chasing the top quartile of cross-sectional data: Is it possible with resistance
      training?
AB  - Resistance exercise is believed to be important for improving several biomarkers
      of health and contributing to decreased all-cause mortality. However, a careful
      examination of the literature reveals a growing body of cross-sectional studies
      finding stronger associations between strength independent of physical activity
      on these various outcomes and biomarkers (i.e., C - reactive protein,
      homocysteine, total cholesterol) of health. Considering that engagement in
      resistance type exercise is associated with an increase in strength, such cross
      sectional data is often used to promote engagement in resistance training. When
      one examines the cross-sectional studies together with the experimental work,
      however, this relationship becomes less clear. For example, being in a higher
      tertile or quartile for grip strength may be associated with more favorable
      biomarkers or health outcomes, yet, experimental work shows that grip strength
      does not change with traditional resistance exercise. This seems to suggest that
      our interpretation and application of this literature may be incorrect. It is our
      opinion that much of the cross-sectional work may more accurately illustrate
      inherent differences between individuals who are "weak" and individuals who are
      "strong". In addition, there is conflicting experimental evidence and a lack of
      longitudinal support that resistance exercise may have a meaningful effect on
      long-term health outcomes. Using this evidence, we present our "human baseline
      hypothesis", which proposes that the baseline value of strength that a person
      possesses prior to training may be a more appropriate indicator regarding long
      term health outcomes than the act of training itself.

PMID- 29055405
TI  - Traumatic brain injury, diabetic neuropathy and altered-psychiatric health: The
      fateful triangle.
AB  - Traumatic brain injury is a detrimental medical condition particularly when
      accompanied by diabetes. There are several comorbidities going along with
      diabetes including, but not limited to, kidney failure, obesity, coronary artery
      disease, peripheral vascular disease, hypertension, stroke, neuropathies and
      amputations. Unlike diabetes type 1, diabetes type 2 is more common in adults who
      simultaneously suffer from other comorbid conditions making them susceptible to
      repetitive fall incidents and sustaining head trauma. The resulting brain insult
      exacerbates current psychiatric disorders such as depression and anxiety, which,
      in turn, increases the risk of sustaining further brain traumas. The relationship
      between diabetes, traumatic brain injury and psychiatric health constitutes a
      triad forming a non-reversible vicious cycle. At the proteomic and psychiatric
      levels, cellular, molecular and behavioral alterations have been reported with
      the induction of non-traumatic brain injury in diabetic models such as stroke.
      However, research into traumatic brain injury has not been systematically
      investigated. Thus, in cases of diabetic neuropathy complicated with traumatic
      brain injury, utilizing fine structural and analytical techniques allows the
      identification of key biological markers that can then be used as innovative
      diagnostics as well as novel therapeutic targets in an attempt to treat diabetes
      and its sequelae especially those arising from repetitive mild brain trauma.

PMID- 29055406
TI  - The role of soluble epoxide hydrolase in preeclampsia.
AB  - Preeclampsia is a serious complication of pregnancy characterized by the
      development of vasospasm, hypertension and often associated with proteinuria
      after the 20th week of gestation. Because termination of pregnancy results in the
      most efficacious resolution of preeclampsia, it is a leading cause of premature
      delivery worldwide. In pregnancy, 14,15-epoxyeicosatrienoic acids (EETs) have
      been shown to facilitate uterine blood flow during preeclampsia, in which the
      classic vasodilator agents such as nitric oxide and prostacyclin are reduced.
      EETs are converted to dihydroxyeicosatrienoic acids (DHETs) by the activity of
      soluble epoxide hydrolase (sEH). We tested the hypothesis that sEH activity is
      increased in preeclampsia by measuring urinary 14,15-DHET in healthy and
      preeclamptic pregnant women. Urine samples were collected and incubated with or
      without beta-glucuronidase to enable the measurement of both the glucuronidated
      and free forms of 14,15-DHET, which were quantified using a 14,15-DHET ELISA.
      Levels of total (free+glucuronidated) 14,15-DHET, which is a measurement of EET
      dependent sEH activity, were higher in urine samples obtained from preeclamptic
      women compared to healthy pregnant women. Considering the fact that
      free+glucuronidated 14,15-DHET levels are increased in urine of preeclamptic
      women, we hypothesize that sEH expression or activity is augmented in these
      patients, reducing EET and increasing blood pressure. Moreover we suggest that
      novel anti-hypertensive agents that target sEH might be developed as therapeutics
      to control high blood pressure in women with preeclampsia.

PMID- 29055407
TI  - The childhood maltreatment influences on breast cancer patients: A second wave
      hit model hypothesis for distinct biological and behavioral response.
AB  - Stress and cancer are two complex situations involving different biological and
      psychological mechanisms. Their relationship have long been studied, and there is
      evidence of the impact stress has on both, development and disease progression.
      Furthermore, early stress has been studied as an important factor associated to
      this relationship, since its impacts on the immune, endocrine and cognitive
      development throughout life is already known. Therefore, understanding early
      stress as a first wave of stress in life is necessary in order to explore a
      possible second wave hit model. From this perspective, we believe that breast
      cancer can be understood as a second wave of stress during development and that,
      in addition to the first wave, can cause important impacts on the response to
      cancer treatment, such as increased chances of disease progression and distinct
      behavioral responses. In this article we propose a second wave hit hypothesis
      applied to breast cancer and its implications on the immune, endocrine and
      cognitive systems, through mechanisms that involve the HPA axis and subsequent
      activations of stress responses.

PMID- 29055409
TI  - JID Connector: Your Link to Content and Colleagues.

PMID- 29055408
TI  - Phosphodiesterases and preeclampsia.
AB  - Antagonizing vasodilation has been considered one of the potential mechanisms
      underlying the pathophysiology of preeclampsia. Phosphodiesterases hydrolyze
      cGMP, interfering with the action of nitric oxide on vascular smooth muscle, thus
      causing vasoconstriction. We hypothesize that the phosphodiesterases in maternal
      plasma, phosphodiesterase-5 in particular, may be linked to clinical
      manifestations in preeclampsia syndrome.

PMID- 29055410
TI  - Getting to the Core of the Dermal Papilla.
AB  - Through coordinated and reciprocal interactions between the epithelium and
      mesenchyme, diverse integumentary organs form and undergo cyclic renewal. The
      hair follicle has become the main model to understand this extraordinary
      regenerative behavior. At the core is the dermal papilla, the organizing center,
      and the epithelial stem cells that respond to dermal papilla signaling. Two
      recent papers by Telerman et al. and Yang et al. unravel new molecular landscapes
      within the dermal papilla.

PMID- 29055411
TI  - Early-Life Gut Dysbiosis: A Driver of Later-Life Fibrosis?
AB  - Using a novel mouse model of scleroderma induced by immunization with
      topoisomerase-I peptide-loaded dendritic cells, Mehta et al. found that early
      life antibiotic exposure resulted in increased later-life fibrosis in the skin
      and lungs. These observations advance the novel concept that gut microbiome
      alterations caused by early-life exposures may contribute to scleroderma
      pathogenesis, and warrant in-depth characterization and validation in
      complementary disease models.

PMID- 29055413
TI  - Pushing the Envelope in Psoriasis: Late Cornified Envelope Proteins Possess
      Antimicrobial Activity.
AB  - Deletion of late cornified envelope (LCE) genes LCE3B and LCE3C (LCE3B/C-del) is
      a psoriasis risk factor linked to the major psoriasis risk gene HLA-C*06. Niehues
      et al. demonstrate that LCE3B/C-del leads to increased keratinocyte LCE3A
      expression. They also show that LCE3A/B/C possess antimicrobial activity but do
      not obviously regulate epidermal barrier integrity. These findings implicate LCE
      proteins in psoriasis pathogenesis via a new functional role.

PMID- 29055412
TI  - Desmoglein 3-Reactive B Cells "Hiding" in Pemphigus Lesions.
AB  - Pemphigus vulgaris is an autoimmune blistering disease caused by anti-desmoglein
      3 IgG autoantibodies. It is accepted that interactions between autoreactive B and
      T cells are key to humoral autoimmunity targeting desmoglein 3. This orchestrated
      process usually occurs in secondary lymphoid organs, including the spleen and
      lymph nodes. Thus, it seems likely that autoreactive B cells reside and produce
      autoantibodies in these tissues. Yuan et al. analyzed lymphocytes in the lesional
      skin of patients with pemphigus vulgaris using several experimental techniques
      and concluded that desmoglein 3-reactive B cells were present. This finding
      expands our understanding of the pathogenesis of pemphigus and should be
      considered when following the clinical course of skin lesions and thinking about
      adjunctive therapy.

PMID- 29055414
TI  - The Challenge of Effective Communication among Scientists.

PMID- 29055415
TI  - Research Techniques Made Simple: Methodology and Applications of Forster
      Resonance Energy Transfer (FRET) Microscopy.
AB  - Classical biochemical techniques have contributed a great deal to our
      understanding of the mechanisms regulating fundamental biological processes.
      However, these approaches are typically end-point, population-based assays and
      are often insufficient in examining transient molecular events. Forster resonance
      energy transfer (FRET) microscopy is a powerful technique capable of
      investigating dynamic interactions between proteins and a plethora of biochemical
      signaling events based on the development of specific biosensors. This technique
      exploits the principle that when FRET occurs, energy from a donor fluorophore is
      transferred to an acceptor fluorophore only when certain conditions are met.
      These include dependence on both distance and fluorophore orientation. In this
      article, applications of FRET microscopy to protein interactions and
      modifications are discussed, and examples are given of the types of biosensors
      that can be developed. There are a number of methods to measure FRET. The most
      common modalities and specific advantages and shortcomings for each are reviewed.
      Finally, general considerations and guidelines for choosing a method are
      discussed.

PMID- 29055416
TI  - SnapshotDx Quiz: November 2017.

PMID- 29055417
TI  - Cells to Surgery Quiz: November 2017.

PMID- 29055420
TI  - Expanding the use of hepatitis C-viremic kidney donors.
AB  - Direct-acting antivirals have revolutionized the treatment of hepatitis C virus
      (HCV) infection in patients with chronic kidney disease, with implications for
      the timing of antiviral treatment among kidney transplant candidates and for the
      use of HCV viremic donors. A recent consensus conference reviewed the available
      data on the safety and cost-effectiveness of expanding access to HCV-positive
      organs to HCV-negative recipients. Early trials are promising, but larger trials
      and a plan for obtaining HCV therapy in the posttransplantation period are
      needed. Implications for the larger transplant community also need to be
      considered.

PMID- 29055419
TI  - The birth of @ISNeducation.

PMID- 29055421
TI  - Magnesium as a new player in CKD: too little is as bad as too much?
AB  - Vascular calcification is a serious complication of chronic kidney disease, but
      the current therapeutic strategy is insufficient for preventing its progression.
      Magnesium is a potent inhibitor of calcification and represents a promising
      therapeutic candidate. Diaz-Tocados and colleagues now demonstrate that magnesium
      supplementation prevents the progression of vascular calcification in a uremic
      rat model, independently of the phosphate-binding capacity. We should keep in
      mind, however, that too much magnesium could have adverse effects on bone
      metabolism.

PMID- 29055422
TI  - Does elastin deficiency cause chronic kidney disease?
AB  - Elastin deficiency in aging and disease is linked to increased vascular stiffness
      and hypertension, which are both associated with chronic kidney disease. Owens et
      al. show that alterations in renal arteries and kidney structure precede or are
      independent of hypertension in elastin haploinsufficient mice. This commentary
      addresses the authors' findings in light of the relationships between elastin
      amounts, vascular stiffness, and pressure wave reflection and transmission in the
      kidney vasculature.

PMID- 29055423
TI  - Going single but not solo with podocytes: potentials, limitations, and pitfalls
      of single-cell analysis.
AB  - Single-cell RNA-sequence (RNA-seq) is a widely used tool to study biological
      questions in single cells. The discussed study identified 92 genes being
      predominantly expressed in podocytes based on a 5-fold higher expression compared
      with endothelial and mesangial cells. In addition to technical pitfalls, the
      question that is discussed in this commentary is whether results of a single-cell
      RNAseq study are able to deliver expression data that truly characterize a
      podocyte.

PMID- 29055424
TI  - A new epitope-tagged Pkhd1 allele sheds light on fibrocystin signaling.
AB  - In this issue of Kidney International, Outeda et al. present a new epitope-tagged
      allele of murine Pkhd1 that allows the monitoring of functional fibrocystin in
      vivo from the extreme C-terminus of the molecule. This work also shows that the
      removal of two-thirds of the intracellular tail of fibrocystin does not result in
      cystogenesis in either the liver or kidney, with major implications for our
      understanding of Pkhd1 function and polycystic kidney disease in general.

PMID- 29055425
TI  - Sensing the texture of imaging, a new biomarker of polycystic kidney disease.
AB  - In autosomal dominant polycystic kidney disease, total kidney volume and age can
      identify patients with progressive disease. Texture analysis of magnetic
      resonance imaging that computerizes and extracts differences in signals that we
      cannot sense visually is now demonstrated as a significant prognostic biomarker
      for the progression of renal decline in autosomal dominant polycystic kidney
      disease. Image analysis holds promise for providing a new dimension for the
      management of autosomal dominant polycystic kidney disease.

PMID- 29055426
TI  - The function of the parathyroid oxyphil cells in uremia: still a mystery?
AB  - Parathyroid glands of young adults consist primarily of chief cells. However,
      with age or after excessive functional stress, another cell type increases
      progressively-the oxyphil cell. There is evidence for a chief-to-oxyphil cell
      transdifferentiation in chronic kidney disease. The latter may represent a
      defense mechanism, transforming the actively secreting chief cells to a less
      actively secreting cell type. However, even if this strategy is able to delay the
      development of secondary hyperparathyroidism, it cannot prevent it.

PMID- 29055427
TI  - Do ANCAs make the difference in lupus nephritis?
AB  - There has been much debate as to whether the distinction between lupus nephritis
      class IV-S and class IV-G is clinically relevant and whether antineutrophil
      cytoplasmic antibodies are pathomechanistically involved because they have been
      associated with the more necrotic and pauci-inflammatory phenotype of lupus
      nephritis that is more often seen in class IV-S. Recent data show that
      antineutrophil cytoplasmic antibody positivity indeed influences the histological
      pattern of lupus nephritis and is associated with worse baseline renal function
      and more active lupus serology.

PMID- 29055428
TI  - Wasp venom-induced acute kidney injury: a serious health hazard.

PMID- 29055429
TI  - The Authors Reply.

PMID- 29055430
TI  - Fetuin-A in the peritoneal effluent of patients with encapsulating peritoneal
      sclerosis-more than a protein?

PMID- 29055431
TI  - Recurrent glomerular diseases after transplantation: more detail for better
      understanding.

PMID- 29055432
TI  - The Authors Reply.

PMID- 29055433
TI  - The Authors Reply.

PMID- 29055434
TI  - Acute renal infarction: a presentation of essential thrombocytosis.

PMID- 29055435
TI  - The Case | Acid-base diagnoses in the 21st century.

PMID- 29055436
TI  - Brain white matter demyelinating lesions and amyotrophic lateral sclerosis in a
      patient with C9orf72 hexanucleotide repeat expansion.
AB  - A hexanucleotide repeat expansion in the C9orf72 gene is associated with
      amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. It has
      been described before four patients with multiple sclerosis (MS) and C9orf72-ALS.
      However, C9orf72 positivity is not associated with increased risk of MS.
      Inflammatory pathways related to NF-kappaB have been linked to ALS and MS, and
      appear to be important in C9orf72-ALS patients. A 42-year-old woman presented
      with progressive bulbar symptoms for 9 months. Neurological examination disclosed
      spastic dysarthria, atrophic tongue with fasciculations, brisk jaw and limb
      tendon reflexes, and bilateral Hoffman sign. Electrophysiological assessment
      confirmed ALS. Brain MRI revealed multiple and bilateral juxtacortical and
      periventricular inflammatory changes, some with gadolinium-enhancement,
      configuring a probable MS-like pattern. CSF evaluation was unremarkable, with no
      oligoclonal bands. Visual and somatosensory evoked potentials were normal. Follow
      up brain MRI 6 months later showed two new lesions in two relatively
      characteristic locations of MS, with no gadolinium-enhancement. Genetic screening
      revealed a C9orf72 expansion. As patient had no clinical manifestation of MS, a
      diagnosis of radiologically isolated syndrome was considered. We speculate that
      these demyelinating lesions might facilitate expressivity of C9orf72 expansion,
      through NF-kappaB activation. This plausible association may lead to the
      identification of a therapeutic target in this subgroup of C9orf72-ALS patients.

PMID- 29055437
TI  - Season of infectious mononucleosis as a risk factor for multiple sclerosis: A UK
      primary care case-control study.
AB  - BACKGROUND: Infectious mononucleosis (IM) and vitamin D deficiency are both risk
      factors for multiple sclerosis (MS). OBJECTIVE: We wished to establish if IM in
      the winter months when vitamin D levels are low may be a greater risk factor for
      MS than IM in the summer months. METHODS: We identified all patients with MS
      diagnosed aged 16-60 in a large primary care database in the United Kingdom and
      matched each by age, sex, general practice and observation period with up to six
      controls. We identified a coded diagnosis of IM prior to the index date (date of
      diagnosis). Logistic regression was used to calculate the odds ratio for prior IM
      exposure in cases versus controls and for winter versus summer exposure in cases
      and controls with prior IM exposure. RESULTS: Based on 9247 cases and 55,033
      matched controls (246 and 846 with prior IM respectively), IM was associated with
      the development of MS (OR 1.77, 95%CI 1.53-2.05) but there was no evidence that
      IM in the winter as opposed to summer was associated with developing MS (OR 1.09,
      95%CI 0.72-1.66). CONCLUSION: We found no evidence that the season of IM
      influences the risk of subsequent MS.

PMID- 29055438
TI  - Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment
      experience with teriflunomide from the Teri-PRO study.
AB  - BACKGROUND: Patient-reported outcomes (PROs) provide clinicians with further
      understanding of the impact of treatment on patients' daily lives. In addition,
      real-world studies, which employ broader inclusion criteria than randomized
      trials, may help to inform prescribing decisions when selecting a disease
      modifying therapy (DMT) to treat relapsing forms of MS (RMS). We sought to use
      PROs to determine patient treatment satisfaction and other treatment outcomes,
      and report safety and tolerability associated with teriflunomide, in the global,
      phase 4 Teri-PRO study (NCT01895335). METHODS: Patients with RMS (N = 1000)
      received teriflunomide for 48 weeks per local labeling. The primary endpoint was
      Global Satisfaction with teriflunomide treatment measured by the Treatment
      Satisfaction Questionnaire for Medication (TSQM, V1.4). Secondary endpoints
      included TSQM scores at Week (W)48 vs baseline in patients switching to
      teriflunomide from other DMTs ('switchers'), additional PROs, and safety.
      RESULTS: Mean TSQM Global Satisfaction score at W48 was high (68.2). Switchers
      reported significant improvements across all four TSQM domains at W48 vs baseline
      (all p < 0.0001). Adverse events were consistent with teriflunomide clinical
      trials. CONCLUSION: Patients reported high treatment satisfaction with
      teriflunomide, with switchers also reporting improved treatment satisfaction vs
      baseline. High treatment satisfaction in patients with RMS may lead to improved
      adherence, and hence treatment outcomes.

PMID- 29055439
TI  - Patient perspectives on neuromyelitis optica spectrum disorders: Data from the
      PatientsLikeMe online community.
AB  - BACKGROUND: Few studies have evaluated patient perspectives on neuromyelitis
      optica (NMO) and NMO spectrum disorder (NMOSD). OBJECTIVE: Describe patient
      reported clinical and treatment experience in NMOSD and compare disease
      characteristics of NMOSD with those of multiple sclerosis (MS). METHODS: This
      retrospective, observational study included 522 members with NMO or NMOSD
      (hereafter collectively referred to as NMOSD) from PatientsLikeMe (PLM), an
      online patient community. Data describing member demographics, symptoms, and
      treatments were collected, analysed descriptively, and compared with data from
      PLM members with MS. RESULTS: Fatigue, pain, and stiffness/spasticity were each
      rated as moderate to severe by more than half of NMOSD members, and 59% reported
      that their health limited the type of work or other activities they could perform
      all or most of the time. Overall, symptom severity and disability levels were
      comparable between NMOSD and MS members; however, NMOSD members were more likely
      than MS members to attribute disability to vision-related symptoms and were less
      likely to report moderate to severe cognitive and emotional symptoms, including
      brain fog, depressed or anxious mood, and emotional lability. CONCLUSION: This
      analysis underscores the challenges of living with fatigue, pain,
      stiffness/spasticity, and visual difficulties, prevalent NMOSD symptoms among
      members of the PLM community.

PMID- 29055440
TI  - Merkel cell carcinoma with fingolimod treatment for multiple sclerosis: A case
      report.
AB  - Neoplasms and reactivation of latent viruses have been observed in individuals
      taking fingolimod. Merkel cell carcinoma (MCC), a rare neuroendocrine skin
      cancer, is associated with immunosuppression and can be triggered by the
      oncogenic Merkel cell polyoma virus (MCPyV). We report a case of a 61-year-old
      man with multiple sclerosis who developed MCPyV-positive MCC 4 years after
      starting fingolimod. This is the second report of MCC associated with MCPyV in an
      individual on fingolimod.

PMID- 29055441
TI  - Clinical and MRI outcomes after stopping or switching disease-modifying therapy
      in stable MS patients: a case series report.
AB  - OBJECTIVE: To evaluate clinical and MRI outcomes after stopping or switching
      disease-modifying therapy in patients with stable MS. METHODS: A retrospective
      chart review was conducted of stable MS patients who discontinued or switched
      their DMT from 2011 to 2015. Clinical and MRI outcomes were obtained at baseline
      and 1-year follow-up. RESULTS: For the DMT discontinuation group, 15 patients
      were included, with 67% female, 53% Caucasian, mean age of 45.3 +/- 12.2 years,
      disease duration of 9.1 +/- 4.3 years, MS type (80% RRMS, 20% SPMS), and EDSS of
      3.7 +/- 1.6. The average duration of stable MS course was 5.5 +/- 3.7 years.
      Within a mean of 6.4 +/- 2.2 months after DMT discontinuation, all 15 patients
      experienced worsening of MS disease. After re-evaluation of MS treatment options,
      all 15 patients were restarted on DMT, of which, 6 (40%) restarted on their prior
      DMT, 4 (26.7%) switched to another DMT due to adverse events on prior DMT, and 5
      (33.3%) switched to a more potent DMT due to worsening of MS activity. One year
      follow-up showed 2 patients (13.3%) who were restarted on their prior DMT
      experienced a relapse and the remaining 13 patients (86.7%) had no clinical or
      MRI activities. For the DMT switch group, 23 patients were included, with 65%
      female, 61% Caucasian, a mean age of 46.9 +/- 11.6 years, disease duration of
      11.7 +/- 5.1 years, MS Type (83% RRMS, 17% SPMS), and EDSS of 3.5 +/- 0.9. After
      switching DMT, 9 (39.1%) patients experienced worsening of clinical or MRI
      outcomes at the 1-year follow-up. Of the 9 switch failures, the majority (N = 6)
      were due to switching to dimethyl fumarate. CONCLUSION: DMT discontinuation in
      stable MS patients resulted in worsening of MS disease course for all patients,
      which improved upon DMT restart or switch. In contrast, 39% of MS stable patients
      experienced worsening of MS disease course when switched to another DMT, with DMT
      selection potentially impacting switch outcomes.

PMID- 29055442
TI  - Partial Vogt-Koyanagi-Harada syndrome as a differential diagnosis of optical
      neuritis.

PMID- 29055443
TI  - Validation of the fatigue scale for motor and cognitive functions in a danish
      multiple sclerosis cohort.
AB  - BACKGROUND: Our objective was to validate the Danish translation of the Fatigue
      Scale for Motor and Cognitive Functions (FSMC) in multiple sclerosis (MS)
      patients. MATERIALS AND METHODS: A Danish MS cohort (n = 84) was matched and
      compared to the original German validation cohort (n = 309) and a healthy control
      cohort (n = 147). The Modified Fatigue Impact Scale (MFIS) was used as reference
      scale and Becks Depression Inventory-Fast Screen (BDI-FS) and Expanded Disability
      Status Scale (EDSS) for confounding factors. We assessed internal consistencies;
      convergent, divergent, and predictive validity; partial correlations correcting
      for depression; significant differences between the mean scores of the cohorts;
      and sensitivity and specificity with receiver operating characteristic (ROC)
      curves. RESULTS: Excellent internal consistencies for the total scale and
      subscales were found (alpha = 0.91-0.95). Strong positive correlations between
      the two fatigue scales implied high convergent validity (total scores: r = 0.851,
      p < 0.01). The two cohorts corresponded well when divided into subgroups (EDSS
      score; age; gender). Correcting for depression did not result in any significant
      adjustments of the correlations. The area under the curve (AUC) for the ROC
      curves represented excellent accuracy (Danish MS cohort, AUC = 0.9190; German MS
      cohort, AUC = 0.9034). CONCLUSION: The Danish translation of the FSMC has a high
      convergent validity with another measure of fatigue as well as excellent internal
      consistency and accuracy. It is found to be an applicable and recommendable
      measure of fatigue in Danish MS patients.

PMID- 29055444
TI  - Progressive multifocal leukoencephalopathy - immune reconstitution inflammatory
      syndrome (PML-IRIS) in liver transplant recipient.
AB  - 65-year-old liver transplant recipient presented with progressive neurologic
      dysfunction. CSF analysis revealed high JC virus load and MRI findings suggested
      the diagnosis of progressive multifocal leukoencephalopathy (PML). Cidofovir and
      mirtazapine were initiated and patient's regular immunosuppressants were reduced.
      Subsequently patient developed left sided hemiplegia, drowsiness and severe
      neglect syndrome. MRI revealed enlargement of PML lesions with contrast
      enhancement and worsening of oedema, consistent with immune reconstitution
      inflammatory syndrome (IRIS). Steroids were initiated and 3 weeks later patient
      showed moderate neurologic improvement. PML-IRIS after solid organ
      transplantation is rarely detected and to the best of our knowledge, this is the
      first reported case of PML-IRIS in a liver transplant recipient.

PMID- 29055445
TI  - Systematic review of depression in patients with multiple sclerosis and its
      relationship to interferonbeta treatment.
AB  - BACKGROUND: Multiple sclerosis is a chronic disease considered the major cause of
      neurological disability in young adults worldwide. While depression is considered
      a determinant factor of impaired quality of life and poorer prognosis among
      patients with multiple sclerosis, it is very often dismissed and undertreated by
      physicians. Depression has been related to treatment with some immunomodulatory
      drugs, such as IFNbeta. Data from patients who committed suicide during the
      pivotal study of interferon used as a disease modifying treatment in multiple
      sclerosis support this association. Moreover, there is plenty of evidence of
      neuropsychiatric toxicity caused by the use of IFNalpha as a treatment for other
      medical conditions. Although this link still remains relatively unknown, the
      presence of warnings regarding the possible relationship between depression and
      IFNbeta led to restriction in medical indications in these patients. The purpose
      of this paper is to try to understand the reasons for an increased prevalence in
      depression in multiple sclerosis and to examine the impact that IFNbeta treatment
      has on their mood. METHODS: We performed a literature search on MEDLINE and
      Google Scholar databases applying PRISMA guidelines for systematic reviews.
      Studies were included if the participants were diagnosed with MS and prescribed
      IFNbeta as the main treatment. We excluded non-english and full-text non
      available papers, as well as the articles where mental health was assessed
      exclusively as a feature of quality of life. The sample includes articles from
      1980 to 2014, although filtration by year of publication was not applied and
      contains data from IFNbeta-1a and IFNbeta-1b. The Cochrane Collaboration Tool
      assessing risk of bias was used to determine the quality of the studies. RESULTS:
      Ten studies met full criteria for inclusion and final data extraction. The
      articles have heterogeneity regarding the samples, the methodology used and the
      expression of the results. Only three studies support the evidence of a
      relationship between depression and interferon, which is statistically
      significant in some patients at the beginning of the treatment. They suggest that
      only patients on IFNbeta treatment with a past history of depression may develop
      a major depression episode during the first six months. The remaining articles
      reviewed (including BENEFIT, BEYOND, and LTF trials) suggest the absence of an
      association. CONCLUSION: The reviewed studies conclude that there is not a clear
      relationship between IFNbeta and depression. A history of depression is a risk
      factor for developing depression during the first 6 months of treatment,
      nevertheless, it is not sufficient to contraindicate it. The development of new
      strategies is crucial for early detection of depressive symptoms. An adequate
      treatment can both improve the mood and deal with the neurological disease by
      increasing treatment adherence and interfering with inflammation. Chronic
      destructive brain changes and serotonergic depletion due to inflammatory factors
      have been proposed as the underlying cause of depression in these patients. It is
      suggested that these patients would have fewer functional reserve remaining to
      deal with stressful life events, which could precipitate a depressive disorder.

PMID- 29055446
TI  - Tackling comorbidity in multiple sclerosis.
AB  - We can improve outcomes in patients with multiple sclerosis (MS) by better
      management of comorbidities. A holistic approach should combine lifestyle
      modifications and the use of low-cost, low-risk treatments for common conditions.
      Such an approach is most effective when all stakeholders share responsibility.

PMID- 29055447
TI  - Commentary on: Neuromyelitis optica spectrum disorder related tonic spams
      responsive to lacosamide - Authors reply.

PMID- 29055448
TI  - A case of MOG antibody-positive bilateral optic neuritis and meningoganglionitis
      following a genital herpes simplex virus infection.
AB  - BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic
      neuritis (ON) and myelitis are recognized as important differential diagnosis of
      aquaporin-4 (AQP4) antibody-positive neuromyelitis optica (NMO)/NMO spectrum
      disorder (NMOSD). Similar to NMO/NMOSD associated with AQP4 antibodies, preceding
      infections have been reported in patients with MOG antibody-positive ON. This is
      the first report of bilateral ON following a herpes simplex virus (HSV) infection
      associated with a positive MOG antibody. CASE PRESENTATION: A 41-year-old man who
      initially presented with genital herpes developed allodynia in the Th2-Th5 and
      Th8-L2 areas, urinary retention, and painful visual loss in the left eye.
      Ophthalmological evaluation and brain magnetic resonance imaging (MRI) revealed
      bilateral ON. A spinal MRI showed leptomeningeal enhancement from the thoracic to
      lumbar vertebrae and abnormal enhancement of the L3 to S3 dorsal root ganglia
      without a change in intramedullary signals. Following treatment with acyclovir
      and steroid pulse, he fully recovered. Serum anti-AQP4 antibodies were negative,
      but anti-MOG antibodies were positive. Finally, he was diagnosed with MOG
      antibody-positive bilateral ON and meningoganglionitis following an HSV
      infection. CONCLUSION: Our case supports a relationship between anti-MOG
      antibodies and ON triggered by an HSV infection. Clinicians should thus consider
      testing for MOG antibodies in patients with post-infectious neurological symptoms
      due to an HSV infection.

PMID- 29055449
TI  - Successful long-term management of spasticity in patients with multiple sclerosis
      using a software application (APP): A pilot study.
AB  - BACKGROUND: Spasticity is a very common syndrome in patients with multiple
      sclerosis (pwMS), but available treatments lead to sufficient symptom control
      only in one third. OBJECTIVE: To investigate the impact of an individualized
      training program on improving spasticity in a prospective pilot trial in pwMS
      suffering from moderate spasticity (defined as >= 4 on a normative rating scale;
      NRS). METHODS: PwMS were familiarized with predefined exercises targeting
      spasticity while undergoing inpatient rehabilitation (IR). After IR, 20 pwMS were
      1:1 randomized either to a newly designed APP-based home therapy program
      providing suitable exercises on a daily basis or to a paper-based home therapy
      program for 3 months. At month 3, all patients received the APP-based home
      program for another 3 months. Degree of spasticity was rated on the NRS. RESULTS:
      Undergoing inpatient rehabilitation for a mean of 32 days led to a significant
      reduction in spasticity in pwMS (p = 0.00). Further self-training with the APP
      based home program for 3 months led to 1.2 lower mean NRS as compared to training
      with the conventional paper-based program (p = 0.09). Spasticity was found to be
      on low levels again in both groups after 6 months. CONCLUSION: In pwMS, an
      individually tailored anti-spasticity program delivered by a software APP is a
      feasible tool for increasing long-term adherence to self-training thereby
      positively impacting spasticity in pwMS.

PMID- 29055451
TI  - The clinical value of Coop/Wonca charts in assessment of HRQoL in a large cohort
      of relapsing-remitting multiple sclerosis patients: Results of a multicenter
      study.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic neurological disease impacting
      patients' health-related quality of life (HRQoL). Since MS specific HRQoL
      questionnaire are often time consuming; thus, simple, feasible and ease
      administering instruments are needed to assess MS HRQoL in clinical practice and
      clinical trials. Hence, aim of our study was to investigated the HRQoL in a large
      cohort of MS patients using the Coop/Wonca charts. METHODS: This was multicenter,
      independent, non-sponsored, observational study, including patients from 40
      Italian MS centers. Inclusion criteria were Expanded Disability Status Scale
      score between 1.0 and 5.5; stable disease at enrolment. HRQoL was assessed, using
      six Coop/Wonca charts for physical fitness, feelings, daily activities, social
      activities, changes in health, health condition, and the Composites Scores of
      Multiple Sclerosis Quality of Life-54 (MSQoL-54), physical health composite
      summary (PHCS) and the mental health composite summary (MHCS). RESULTS: Out of
      648, 593 relapsing-remitting MS patients, 415 (70%) women, mean age years, 417
      (70%) were finally enrolled. We found a inter-rater agreement of 0.8, ranging
      from 0.64 to 0.91, as expressed by the alpha coefficient. Intra-rater agreement
      was 0.82, ranging from 0.78 to 0.96. Coop/Wonca charts were scored with a Likert
      method from one to five (corresponding to best and worst HRQoL respectively).
      According to this scoring, study population was stratified into three categories
      (score 1-2 corresponding to better HRQoL; score 3 corresponding to neutral
      profile; score 4-5 corresponding to worse HRQoL). Coop/Wonca charts resulted
      significantly correlated with PHCS and with MHCS.

PMID- 29055450
TI  - Management of infusion related reactions associated with alemtuzumab in patients
      with multiple sclerosis.
AB  - OBJECTIVE: Infusion-associated reactions (IARs) occur in >90% patients with
      multiple sclerosis (MS) treated with alemtuzumab. We aimed to study the frequency
      of IARs at 2 sites using 5 days of steroids (1g/day of IV methylprednisolone),
      but otherwise distinct protocols. METHODS: This was retrospective chart review of
      38 consecutive MS patients who were treated with alemtuzumab from June 2015 till
      February 2017 at Department of Neurology, University Hospital Center Zagreb,
      Croatia and Department of Neurology, University Medical Center Ljubljana,
      Slovenia. RESULTS: Seventeen patients (44.7%) did not experience IARs. Skin
      reactions and fever were the most common IARs attributed to alemtuzumab infusions
      and they were most frequent on Day 5 and Day 1, respectively. We have observed
      significant differences in the occurrence of fever (p = 0.005) depending on the
      site of alemtuzumab administration which could be explained by different
      antipyretics used; fever was absent in the Slovenian cohort because high dose
      intravenous metamizole was administered. Two out of 9 treatment naive, and 19 out
      of 29 patients who previously received immunomodulatory treatment had IARs (chi2
      = 5.208, p = 0.022). CONCLUSION: Modified premedication scheme consisting of
      1g/day of IV methylprednisolone throughout all 5 days of alemtuzumab treatment
      may reduce overall IARs. Intravenous administration of antipyretics may work
      better than oral administration.

PMID- 29055453
TI  - Response to: S. Sega-Jazbec et al.: "Management of infusion related reactions
      associated with alemtuzumab in patients with multiple sclerosis" Multiple
      Sclerosis and Related Disorders 2017.

PMID- 29055452
TI  - Validation of an environmentally-friendly and affordable cardboard 9-hole peg
      test.
AB  - BACKGROUND: In multiple sclerosis (MS) upper limb neurological impairments, are
      an important driver of disability and handicap. The gold standard for assessing
      upper limb function is the 9-hole peg test (9HPT). One disadvantage of the
      current plastic version is its price, which prevents its widespread use as a self
      monitoring tool by the MS community. OBJECTIVE: To develop and validate an
      affordable cardboard version of 9HPT for patients to self-monitor upper limb
      function at home. The aim is not to replace the plastic version, which would stay
      the gold standard in MS centers. METHODS: We enrolled 177 volunteers, 68 healthy
      controls and 109 people with MS (pwMS) at varying stages of their disease.
      Volunteers performed two trials of the 9HPT with their dominant hand and two with
      their non-dominant hand using both plastic 9HPT and cardboard 9HPT. The primary
      comparison parameter was the time needed to perform the task. RESULTS: The mean
      score for the cardboard 9HPT was 24.58 (SEM 1.54s) seconds compared to 26.03 (SEM
      1.44s) seconds for the plastic 9HPT (p = 0.007). However, the two versions of the
      tests correlated very strongly, r = 0.96 (p < 0.001). The coefficient of
      variation, repeat-repeat testing, showed less variability with the cardboard
      version than in the plastic one with 10% and 14%, respectively. Two-thirds of
      pwMS preferred using the cardboard version. CONCLUSION: This study demonstrates
      that the cardboard version is at least equivalent to the plastic version of the
      test with arguably better design attributes making it the preferred option for
      self-monitoring.

PMID- 29055454
TI  - Spontaneous yawning in patients with multiple sclerosis: A polygraphic study.
AB  - BACKGROUND: Patients with multiple sclerosis (MS) suffer from the repetitive
      yawning and sleep problems. Yawning is observed in MS and other central nervous
      system disorders and yawning and swallowing may be controlled by the network of
      the brain stem. Therefore it is important to investigate the MS patients with
      various clinical and radiological locations in order to understand the role of
      brainstem on the yawning mechanisms. One hour polygraphic recording would be
      crucial method for this purpose, because it is easy to observe spontaneous
      yawning (SY) and spontaneous swallowing (SS) together with their
      electrophysiologic counterparts. Previous studies reported that contagious yawn
      and swallow are temporally related and frequency of swallows was increased within
      10s of post yawn period in normal adult subjects. We have re-investigated this
      phenomenon by studying the SY and SS in polygraphic recording in normal subjects
      and patients with MS. Then we hypothesized that SY is expected to be increased in
      MS patients. METHODS: 49 patients with MS and 19 control subjects were recruited
      in this study. We used a twelve-channel electroencephalography (EEG) device. Five
      channels were for electromyography (EMG) recording. We also used one channel for
      laryngeal sensor for vertical movements of the larynx during swallowing. Cardiac
      rhythm, respiration and sympathetic skin responses were synchronously recorded
      during swallowing. We evaluated rate of total SY, swallows inside the yawning,
      before and after 10s of the yawning and yawning unrelated with swallowing.
      RESULTS: Patients with MS yawned more frequently than healthy controls (p =
      0,044). It was obvious that the yawning unrelated with spontaneous swallow was
      also significantly increased compared to normal controls (p = 0,047), whereas
      swallowing inside the yawn or before and after 10s of yawning were not
      significantly different in both groups. Among 49 MS patients, 16 (32.6%) had
      brainstem involvement. Yawning was observed in only 6 (37.5%) of them.
      CONCLUSION: Yawning is significantly increased in MS patients compared to normal
      controls by using the polygraphic method. There is no direct relation of the
      brainstem and the origin of yawning in MS patients according to clinical picture
      and MRI findings. However safe swallows during yawning could suggest that there
      is still need to some brain stem mechanism and/or oropharyngeal reflexes.
      Difficulties must be emphasized to detect anatomic localization in MS because of
      relapsing pattern of disease.

PMID- 29055455
TI  - Deconstructing the symbol digit modalities test in multiple sclerosis: The role
      of memory.
AB  - BACKGROUND: The Symbol Digit Modalities Test (SDMT) is a sensitive measure of
      impaired cognition in people with MS. While the SDMT is primarily considered a
      test of information processing speed, other components such as visual scanning
      and oral-motor ability have also been linked to performance. The objective of
      this study was to determine the role of memory in the performance of the SDMT.
      METHODS: Two version of a modified computerized SDMT (c-SDMT) were employed, a
      fixed and a variable. For each group 50 MS and 33 healthy control (HC)
      participants were recruited. In the fixed c-SDMT, the symbol-digit code is kept
      constant for the entire test whereas in the variable version, it changes eight
      times. Unlike the traditional SDMT which records the correct number of responses,
      the c-SDMT presented here measures the mean response time (in seconds) for the
      eight trials. RESULTS: MS participants were slower than HC on the fixed (p <
      0.001) and variable (p = 0.005) c-SDMT. Trend analysis showed performance
      improvement on the fixed, but not on the variable c-SDMT in both MS and HC
      groups. Furthermore, immediate visual memory recall was associated with the fixed
      (beta = -0.299, p = 0.017), but not variable (B = -0.057, p = 0.260) c-SDMT.
      Immediate verbal memory was not associated with either versions of the c-SDMT.
      CONCLUSIONS: Given that the fixed and variable c-SDMTs are identical in every way
      apart from the fixity of the code, the ability of participants to speed up
      responses over the course of the fixed version only points to the contribution of
      incidental visual memory in test performance.

PMID- 29055456
TI  - Vitamin B12, folate, and homocysteine levels and multiple sclerosis: A meta
      analysis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a demyelinating and disabling inflammatory
      disease of the central nervous system. Several factors contribute to MS
      pathogenesis including genetic-environmental interactions. Case-control studies
      suggest that there might be associations between MS and homocysteine (Hcy),
      vitamin B12, and folate blood levels. AIM: To meta-analyze all available data
      describing associations between MS and serum or plasma Hcy, vitamin B12, and
      folate levels. METHODS: The PubMed, MEDLINE, and EMBASE databases were searched
      for eligible case-control studies published until June 2017. After data
      extraction, separate analyses using mainly random-effects models were conducted
      to test for associations between MS and vitamin B12, Hcy, or folate blood levels.
      RESULTS: Twelve, 12, and 9 studies met the inclusion criteria for meta-analysis
      of MS and Hcy, vitamin B12, and folate levels, respectively. The standardized
      mean difference (SMD) between MS patients and controls was statistically
      significant for Hcy (SMD: 0.70, 95% CI: 0.06, 1.34). Stratification according to
      clinical pattern did not reveal significant differences between relapsing
      remitting MS patients and controls (SMD: 0.30, 95% CI: -0.93, 1.54) or between
      secondary progressive MS patients and controls (SMD: 0.12, 95% CI: -1.65, 1.90).
      There were no significant differences in SMD between MS patients and healthy
      individuals for vitamin B12 (SMD: -0.09, 95% CI: -0.29, 0.10) or folate (SMD: 
      0.06, 95% CI: -0.17, 0.05). CONCLUSION: MS patients tend to have elevated Hcy
      blood levels compared to healthy controls. Hcy may contribute to the pathogenesis
      of the disease.

PMID- 29055458
TI  - The walking speed reserve in low disabled people with multiple sclerosis: Does it
      provide greater insight in detecting mobility deficits and risk of falling than
      preferred and fast walking speeds?
AB  - The extent of an increase from a preferred walking speed (PWS) to a fast walking
      speed (FWS) is defined as the walking speed reserve (WSR). The WSR is unique as
      it reflects an individual's ability to increase their walking speed on demand.
      The primary objective of this study was to examine whether the WSR was more
      advantageous than the PWS and FWS in terms of reflecting mobility deficits and
      risk of falling associated with multiple sclerosis (MS). The patient group
      included 235 people with MS (PwMS) (139 women) with a mean age of 43.6 (SD =
      13.6) years. The WSR, PWS and FWS (m/s) were: 0.47 (SD = 0.29), 0.98 (SD = 0.28)
      and 1.45 (SD = 0.47), respectively. Significant correlation scores were found
      between the WSR and all clinical walking and balance outcome measures; Pearson's
      rho ranged from 0.240 to 0.517. However, stronger correlation scores were found
      between the PWS, FWS and all clinical walking and balance outcome measures with
      the Pearson's rho ranging from 0.415 to 0.797. In terms of fall status, non
      significant differences were observed between the fallers (n = 133) and non
      fallers' (n = 102) groups with respect to the WSR scores. We found that the PWS
      and FWS were more instructive measures for assessing mobility deficits and fall
      status in PwMS than the WSR. Nevertheless, we do not rule out the possibility
      that the WSR score may be a preferred predictor of other adverse events related
      to MS, such as lower limb muscle weakness, spasticity and aerobic capacity.

PMID- 29055457
TI  - Anti-aquaporin-4 titer is not predictive of disease course in neuromyelitis
      optica spectrum disorder: A multicenter cohort study.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune
      disease associated with a serological antibody to aquaporin-4 (AQP4) detectable
      in up to 80% of patients. The enzyme-linked immunosorbent assay (ELISA) is one of
      the most popular methods of testing for anti-AQP4 antibodies that results with a
      titer in which < 3 Units/ml is negative, 3-5 is borderline and 5+ is positive.
      The value of the positive titer in predicting long term disease course is
      currently unknown. METHODS: This is a retrospective analysis of NMOSD patients
      from five centers around the world: Baltimore, USA, Philadelphia, USA, Shanghai,
      China, Berlin, Germany, and Medellin, Columbia, where ELISA titers on anti-AQP4
      antibody testing is available. Inclusion criteria include a diagnosis of NMOSD
      and seropositive anti-AQP4 antibody test with titer = /> 3 Units/ml. Patients
      were stratified into three groups by titer: 3-30 Units/ml (low), 31-100 Units/ml
      (medium), and 101+ Units/ml (high). Demographic factors such as age at onset,
      race, and sex were collected along with clinical features such as annualized
      relapse rate, duration of disease, location of relapses, and treatment history.
      RESULTS: A total of 139 NMOSD patients met criteria for inclusion in this study,
      stratified into three groups by titer: 42 subjects with low titers of 3-30
      Units/ml, 30 subjects with medium titers of 31-100 Units/ml and 67 subjects with
      high titers of 101 or greater ELISA Units/ml. The average age at onset, sex and
      race distribution were not significantly different among the groups. The number
      of patients untreated in each group was similar (< 25%) as was the average
      annualized relapse rate (0.591-0.821 relapses/year). With an average of 10 years
      follow up, the average disability level was not different among the three titer
      groups (EDSS range 3.03-3.48). The distribution of lesions, as well as their
      preventive treatment regimens did not differ significantly. CONCLUSION: Beyond a
      positive/borderline/negative result, the titer of the anti-AQP4 antibody ELISA
      assay is not predictive in the disease course for patients with NMOSD. Low titer
      patients experience the same disease course as medium-titer and high-titer anti
      AQP4 antibody patients with NMOSD.

PMID- 29055459
TI  - Smoking and multiple sclerosis: A systematic review and meta-analysis using the
      Bradford Hill criteria for causation.
AB  - BACKGROUND: Despite being one of the most common neurological disorders globally,
      the cause(s) of multiple sclerosis (MS) remain unknown. Cigarette smoking has
      been studied with regards to both the development and progression of MS. The
      Bradford Hill criteria for causation can contribute to a more comprehensive
      evaluation of a potentially causal risk factor-disease outcome relationship. The
      objective of this systematic review and meta-analysis was to assess the
      relationship between smoking and both MS risk and MS progression, subsequently
      applying Hill's criteria to further evaluate the likelihood of causal
      associations. METHODS: The Medline, EMBASE, CINAHL, PsycInfo, and Cochrane
      Library databases were searched for relevant studies up until July 28, 2015. A
      random-effects meta-analysis was conducted for three outcomes: MS risk,
      conversion from clinically isolated syndrome (CIS) to clinically definite
      multiple sclerosis (CDMS), and progression from relapsing-remitting multiple
      sclerosis (RRMS) to secondary-progressive multiple sclerosis (SPMS). Dose
      response relationships and risk factor interactions, and discussions of
      mechanisms and analogous associations were noted. Hill's criteria were applied to
      assess causality of the relationships between smoking and each outcome. The
      effect of second-hand smoke exposure was also briefly reviewed. RESULTS: Smoking
      had a statistically significant association with both MS risk (conservative:
      OR/RR 1.54, 95% CI [1.46-1.63]) and SPMS risk (HR 1.80, 95% CI [1.04-3.10]), but
      the association with progression from CIS to CDMS was non-significant (HR 1.13,
      95% CI [0.73-1.76]). Using Hill's criteria, there was strong evidence of a causal
      role of smoking in MS risk, but only moderate evidence of a causal association
      between smoking and MS progression. Heterogeneity in study designs and target
      populations, inconsistent results, and an overall scarcity of studies point to
      the need for more research on second-hand smoke exposure in relation to MS prior
      to conducting a detailed meta-analysis. CONCLUSION: This first review to
      supplement systematic review and meta-analytic methods with Hill's criteria to
      analyze the smoking-MS association provides evidence supporting the causal
      involvement of smoking in the development and progression of MS. Smoking
      prevention and cessation programs and policies should consider MS as an
      additional health risk when aiming to reduce smoking prevalence in the
      population.

PMID- 29055460
TI  - Visual pathway involvement in multiple sclerosis: Look straight in the eyes.
AB  - Visual symptoms are a common clinical manifestation of multiple sclerosis (MS)
      and are frequently due to acute optic neuritis (ON). However, the entire visual
      pathway can be involved throughout the disease course. We describe the case of a
      young MS patient who experienced visual symptoms that were eventually found to be
      caused by retinal periphlebitis, an inflammatory process of the anterior visual
      pathway, which is common during MS, but rarely symptomatic. This case reinforces
      the concept that in all MS patients complaining visual symptoms, a complete work
      up should be performed in order to rule out possible ON mimicries.

PMID- 29055461
TI  - Sativex in the management of multiple sclerosis-related spasticity: An overview
      of the last decade of clinical evaluation.
AB  - BACKGROUND: Spasticity is a common symptom of multiple sclerosis (MS) affecting
      about 80% of MS patients. Numerous lines of evidence suggest that spasticity due
      to its complexity is not adequately managed with conventional anti-spastic
      therapies. Therefore, in order to improve the outcomes for the majority of MS
      patients, alternative approaches are needed to be discovered. Over the last
      years, the use of cannabinoid compounds as a potential treatment for MS-related
      symptoms has aroused great interest, owing to encouraging preclinical and
      clinical studies. To date, Sativex, an oromucosal spray containing
      tetrahydrocannabinol and cannabidiol in approximately 1:1 ratio, is the only
      commercially available formulation containing cannabinoids used as add-on therapy
      for treatment of spasticity in adult MS patients who are not responding to
      conventional antispastic therapies. METHODS: Here, by performing a literature
      search, we provided an overview of the last decade of clinical evaluations as
      well as post-marketing studies about effectiveness and safety of Sativex in the
      management of MS-related spasticity. RESULTS: Sativex was proven effective in
      treating spasticity and also in improving the patient's quality of life. In
      addition, a low incidence of adverse reactions Sativex-related supports the good
      safety profile and its tolerability. CONCLUSION: This review by recognizing the
      clinical effectiveness of Sativex in spasticity management, opened a new
      opportunity for many patients with spasticity resistant to common antispastic
      drugs.

PMID- 29055462
TI  - Elevated cardiovascular risk factors in multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is associated with elevated cardiovascular
      mortality. To prevent this a better understanding of their CVD risk factors and
      interrelations is necessary. METHODS: MS patients (n = 52) and healthy controls
      (HC, n = 24) were matched for age, height, weight, body mass index and physical
      activity. Body composition, resting blood pressure (BP), resting heart rate (HR),
      glucose tolerance, HbA1c, blood lipids (HDL, LDL, total cholesterol, triglyceride
      concentrations) and c-reactive protein concentrations were analyzed. Regression
      analyses identified independent CVD risk factors and their interrelations in MS.
      RESULTS: In MS and compared to HC, fat mass (25.1 +/- 1.2kg vs. 17.9 +/- 1kg),
      fat percentage (33.8 +/- 1.2% vs. 28.4 +/- 1.5%), systolic (130 +/- 1.8mmHg vs.
      120 +/- 2.9mmHg) and diastolic (79 +/- 1.1mmHg vs. 71 +/- 1.9mmHg) BP, resting HR
      (72 +/- 1.4bpm vs. 60 +/- 2bpm), blood triglycerides (113.8 +/- 8.6mg/dl vs. 98.2
      +/- 17.4mg/dl), fasting (13.5 +/- 2.9mU/l vs. 7.2 +/- 0.8mU/l) and 2h insulin
      (71.9 +/- 12.5mU/l vs. 35.8 +/- 8.1mU/l), 2h glucose (6.3 +/- 0.5mmol/l vs. 4.8
      +/- 0.5mmol/l) and HOMA index (3.7 +/- 1.1 vs. 1.7 +/- 0.2) were significantly (p
      < 0.05) elevated. Total cholesterol, blood HDL and LDL concentrations did nog
      differ between groups (p < 0.05). Regression analyses indicated that MS is
      independently associated with elevated fat mass/percentage, systolic and
      diastolic BP and HR and in MS fat mass appears to be an independent contributor
      of the other measured CVD risk factors in MS. CONCLUSION: Persons with MS have an
      increased risk for CVD and fat mass appears to be an important risk factor.
      Therefore, normalizing whole body fat should be an essential part of MS
      treatment.

PMID- 29055463
TI  - Improvement of postural control in individuals with multiple sclerosis after a
      single-session of ball throwing exercise.
AB  - BACKGROUND: Deficit in balance control is a common and often an initial disabling
      symptom of multiple sclerosis (MS). We investigated the role of short-term
      training in improvement of anticipatory postural adjustments (APAs) and its
      effect on subsequent control of posture in individuals with MS. METHODS: A pre
      post feasibility study involved eight individuals with relapsing-remitting MS who
      participated in the laboratory tests before and after a single training session
      consisting of throwing a medicine ball. The outcome measures including
      electromyographic activity of trunk and leg muscles and center of pressure
      displacements were recorded and analyzed during the anticipatory and compensatory
      phases of postural control. RESULTS: The training resulted in enhancement of the
      generation of APAs seen as significantly earlier onset of leg and trunk muscle
      activity prior to the bilateral arm flexion task (p < 0.05). Significantly early
      activation of postural muscles was also observed prior to the predictable
      external perturbation, the task that was not a part of training, indicating the
      transfer of the effect of the single training session. Postural control during
      the balance restoration phase was improved after training (p < 0.05). CONCLUSION:
      The observed training-related improvements of balance control suggest that
      focused rehabilitation could be effective in improving postural control.
      Consequentially, this could enhance mobility and quality of life in the
      individuals with MS.

PMID- 29055464
TI  - Autosomal dominant leukodystrophy presenting as Alzheimer's-type dementia.
AB  - Autosomal dominant leukodystrophy is a neurodegenerative disorder caused by
      either point mutations or duplication of the lamin B1 gene on chromosome 5q23.
      The typical clinical picture consists of autonomic symptoms as well as cerebellar
      and pyramidal signs. Here we present the case of a 57-year-old female referred to
      our clinic due to cognitive decline. Neurological examination was significant for
      cognitive impairment as well as pyramidal and cerebellar signs. Brain MRI
      displayed diffuse hyperintense lesions in the subcortical white matter, pontine
      nuclei, brachium pontis and restiform body. The diagnosis was confirmed via
      genetic testing. Autosomal dominant leukodystrophy should be included in the
      differential diagnosis of patients presenting with cognitive impairment, motor
      signs, and leukodystrophy-like images.

PMID- 29055465
TI  - Radiologically isolated syndrome and multiple sclerosis.
AB  - BACKGROUND: Incidental white matter lesions (WML) are increasingly seen on brain
      magnetic resonance imaging (MRI) in clinical practice. Demyelination consistent
      with MS is seen in 0.1-0.7% of the population as evident by autopsy and MRI
      studies. The term radiologically isolated syndrome (RIS) was coined to define a
      subgroup of patients with demyelinating lesions highly suggestive of multiple
      sclerosis (MS). The Okuda criteria for diagnosing RIS help in stratifying the
      risk of conversion to MS but RIS is still not considered a distinct MS phenotype.
      METHODS: The authors reviewed the current literature on diagnostic criteria,
      natural history and treatment indications in RIS, to assess the challenges faced
      in diagnosing and treating such patients in clinical practice. RESULTS:
      Typically, one-third of patients convert to clinically definite MS within 5
      years, with some progressing directly into primary progressive MS (PPMS). The
      main risk factors for conversion are: age < 37 years, male gender and presence of
      spinal cord lesions. Patients with RIS have evidence of early axonal loss, brain
      atrophy, cognitive deficits, increased anxiety and depression, and subclinical
      inflammatory disease. CONCLUSION: Patients with RIS at high risk of clinical
      conversion might be considered for treatment, although this is still a
      controversial issue. Prospective follow-up of RIS patients by an MS specialist is
      recommended.

PMID- 29055466
TI  - A disease in the age of the web: How to help people with Multiple Sclerosis in
      social media interaction.

PMID- 29055467
TI  - Diagnostic evaluation of dysphagia in multiple sclerosis patients using a Persian
      version of DYMUS questionnaire.
AB  - BACKGROUND: Multiple sclerosis is a chronic neurological disease that may cause
      swallowing disorders. Dysphagia is a common problem, which patients with
      different levels of disability may encounter, but it is usually underestimated;
      therefore, effective assessments need to be performed before any serious
      complications. The aim of this study was to identify the frequency and
      characteristics of dysphagia in multiple sclerosis patients of Khuzestan MS
      society, using a Persian version of Dysphagia in Multiple Sclerosis (DYMUS)
      questionnaire. METHOD: 105 consecutive MS patients (84 F and 21 M, mean age 33.8
      +/- 8.5 years, mean disease duration 3.5 +/- 3.1 years, mean Expanded Disability
      Status Scale (EDSS) 1.8 +/- 1.3) participated in the study and the DYMUS
      questionnaire was administered by a trained speech therapist. RESULTS: The
      results have shown that 55 MS patients (52.4%) had dysphagia and the dysphagia
      was significantly associated with the disease course of MS (p = 0.02). However,
      significant associations between DYMUS values and EDSS, disease duration, age,
      and gender were not observed. (Respectively, p = 0.4, p = 0.09, p = 0.1, p =
      1.0). In the dysphagia group, based on dysphagia severity, 17.1% and 35.2% of
      patients had mild and alarming dysphagia, respectively. Although, the patients
      with alarming dysphagia had longer disease duration, higher EDSS score and more
      with SP, PP and PR disease course than the patients with mild dysphagia, these
      differences were not significant. CONCLUSION: The oropharyngeal dysphagia in MS
      patients is very common even in early stages of the disease; therefore, it is
      important to assess these patients carefully and to initiate a treatment program
      if needed.

PMID- 29055468
TI  - Evaluation of lithium serum level in multiple sclerosis patients: A
      neuroprotective element.
AB  - INTRODUCTION: It has been claimed that continuous and high production of nitric
      oxide (NO) and its metabolites may be involved in the pathogenesis of several
      neurological disorders such as multiple sclerosis. A number of studies have
      demonstrated that lithium regulates NO levels in disorders of the central nervous
      system. The aim of this study was to investigate whether NO as a marker of
      disease activity is correlated with lithium deficiency in relapsing remitting
      multiple sclerosis (RR-MS). METHODS: This case-controlled study comprised 44
      patients with RR-MS and 43 healthy subjects matched by age, gender, smoking
      status, and body mass index. The Griess reaction was used to measure the NO
      metabolites, nitrite and nitrate in serum. In addition serum lithium levels were
      measured using atomic absorption spectrometry method. The mean serum NO
      concentrations in the groups RR-MS and the control were 18.5 +/- 3.1uM and 15.5
      +/- 2.9uM, respectively. Data analysis showed a statistically significant
      difference between subjects with RR-MS and the control group (p < 0.05).
      Furthermore, serum lithium concentrations in RR-MS (0.57 +/- 0.2) were remarkably
      lower in RR-MS patients than the controls (2.29 +/- 0.7) (p < 0.05). CONCLUSION:
      The present findings suggest that lithium deficiency may upregulates NO
      production in RR-MS. Further studies with larger samples are needed to confirm
      the effects of lithium treatment on NO pathway and its association with synaptic
      plasticity in RR-MS patients.

PMID- 29055469
TI  - Clinically isolated syndromes or clinically isolated patients? A patient and
      clinician perspective on the utility of CIS as a diagnosis.
AB  - BACKGROUND: The term "Clinically Isolated Syndrome" (CIS) was introduced to
      describe a first clinical neurologic episode suggestive of an inflammatory
      demyelinating CNS disorder. Thereafter, the risk of developing clinically
      definite multiple sclerosis ranges from 20% to 80%, depending on a number of
      prognostic factors. Although the concept of CIS has been an important component
      in improving our understanding of risk levels in Multiple Sclerosis and
      prognosis, communicating uncertainty in this context remains a challenge for both
      patients and their clinicians. We therefore wished to explore both the patients
      understanding of the concept of CIS and the subsequent impact of a diagnosis. We
      also explored the concept of CIS from the clinician's perspective. METHODS: The
      study uses a qualitative descriptive design involving both a semi-structured
      interview of patients with CIS as well as a short questionnaire sent to
      practising clinicians in the Republic of Ireland. Narrative data was coded onto
      themes. RESULTS: Thirty CIS patients were interviewed. The majority of patients
      understood the term "CIS" but not the link between CIS and MS. Two themes were
      identified: emotional reactions following CIS diagnosis; and terminology and
      communication. Confusion and anxiety among patients due to inconsistent
      communication of CIS was identified. Of the thirty-three clinicians surveyed,
      only thirty-nine per cent found the term "CIS" clinically useful. Eighteen per
      cent of clinicians diagnosed MS from the CIS case vignette provided. CONCLUSION:
      In the diagnosis of a first demyelinating event, use of the term "CIS" is
      confusing to patients and inconsistent among clinicians. We suggest that the term
      "CIS" be abandoned in favour of terminology that reflects both its pathogenesis
      and inherent risk of subsequent MS.

PMID- 29055470
TI  - Commentary on: Neuromyelitis optica spectrum disorder related tonic spams
      responsive to lacosamide.

PMID- 29055471
TI  - Consistent efficacy of daclizumab beta across patient demographic and disease
      activity subgroups in patients with relapsing-remitting multiple sclerosis.
AB  - BACKGROUND: Daclizumab beta is a humanized monoclonal antibody specific for the
      human interleukin-2 receptor alpha chain (CD25). In two pivotal studies in
      relapsing multiple sclerosis (MS), patients treated with daclizumab beta
      exhibited lower annualized relapse rates (ARR) when compared with placebo or with
      intramuscular (IM) interferon beta-1a. OBJECTIVES: To determine if the efficacy
      of daclizumab beta demonstrated in the phase 2 SELECT study and the phase 3
      DECIDE study was consistent in patient subgroups. METHODS: In the SELECT study,
      patients received daclizumab beta 150 or 300mg administered subcutaneously every
      4 weeks for 52 weeks, and were compared with patients who received placebo. In
      the DECIDE study, patients received daclizumab beta 150mg administered
      subcutaneously every 4 weeks for 96-144 weeks, and were compared with patients
      who received IM interferon beta-1a 30ug. Subgroups were defined by sex, age, the
      number of relapses in the year before the study, disease duration, baseline
      disability measured by EDSS, presence of Gd-enhancing lesions, T2 hyperintense
      lesion volume at baseline, and previous interferon beta-1a use. RESULTS:
      Treatment with daclizumab beta was associated with relative lower ARR, with 95%
      confidence intervals (CIs) below 1 in 13 of 15 subgroups (SELECT study) compared
      with placebo and in all 17 subgroups compared with interferon beta-1a (DECIDE
      study). In 2 subgroups in the SELECT study (patients who were older than 35 years
      of age or who had a disease duration of 10 or more years), the rate ratio point
      estimate for the ARR was in favor of daclizumab beta but the 95% CI overlapped
      with 1. The clinical benefits in ARR achieved with daclizumab beta treatment
      compared with placebo or interferon beta-1a across subgroups were similarly
      supported by reductions in lesion activity on magnetic resonance images (MRIs).
      CONCLUSIONS: These findings suggest that treatment with daclizumab beta is
      consistently effective among clinically important patient subgroups and support
      its potential as a viable therapeutic option across the spectrum of relapsing MS.

PMID- 29055472
TI  - Human glutathione s-transferase enzyme gene variations and risk of multiple
      sclerosis in Iranian population cohort.
AB  - Multiple sclerosis (MS) is an inflammatory disease with unknown etiology.
      Oxidative stress has been demonstrated to play a role in pathological and
      inflammatory mechanisms of MS. Cells activate antioxidant processes in response
      to oxidative stress. Glutathione is one of the antioxidant agents in the brain
      and serves as a cofactor for glutathione s-transferase (GST) enzymes for
      detoxifying nerve cells. Among different classes of GST, GSTM1 and GSTT1 are
      associated with the loss of function due to structural homozygous deletion. The
      aim of this study is to investigate GSTM1 and GSTT1 null genotypes in an Iranian
      population. In this study, 270 patients and 250 healthy controls were
      investigated. Patient's disabilities were assessed by Kurtzke Expanded Disability
      Status Scale (EDSS) and genotypes were determined by multiplex PCR. Association
      between genotype and MS, type of MS, gender, and inability level were surveyed.
      The findings demonstrated a highly significant association between the null
      genotypes and MS (OR = 6.89 for M1/T1). The combination of two genotypes
      increased the risk of MS by 6.8 times. The null genotypes were found to be more
      frequent in women than in men. Moreover, a significant association was observed
      between the null genotype and EDSS 6-10 (OR = 3.199). No significant association
      was noticed between MS type and the studied genotypes. According to this study,
      it can be proposed that people with GSTM1 and GSTT1 deletions are at a higher
      risk for developing MS, which can be due to a decrease in enzymatic activity and
      their levels in nerve cells and the brain.

PMID- 29055474
TI  - Gender differences among Chinese patients with neuromyelitis optica spectrum
      disorders.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune,
      inflammatory demyelinating diseases of the central nervous system, which have
      established variations in prevalence across different ethnicities and genders.
      The objective of this study was to investigate differences in clinical features
      among men and women with NMOSD, according to the 2015 diagnostic criteria.
      METHODS: A total of 97 patients with NMOSD were recruited from inpatient
      neurology clinics in this retrospective study. Demographic and clinical data were
      extracted from the various databases. Data on epidemiology, clinical signs,
      initial symptoms, and laboratory indices of men and women with NMOSD were
      compared. RESULTS: The cohort of this study had a female/male ratio of 5.47:1,
      with annualized relapse rates of 0.72 in female and 0.56 in male patients. Among
      female patients, 29.2% and 53.6% initially experienced acute optic neuritis and
      acute myelitis, respectively, while the prevalence of these symptoms was 46.6%
      and 53.3% among male patients. A total of 14.6% and 2.4% of female patients had
      area postrema symptoms and other brainstem signs, respectively on study
      enrollment. The prevalence of anti-AQP4-autoantibodies and anti-thyroid
      peroxidase autoantibodies/anti-thyroglobulin autoantibodies (TPO/TG-Ab) was
      significantly higher among women (77% and 45.7%) than among men (46.1% and 13.3%)
      (P < 0.05 for both comparisons). A total of 11 women with NMOSD (11.3% of the
      cohort) also had autoimmune diseases. CONCLUSIONS: Women with NMOSD have higher
      morbidity levels than men with this disease and are more likely to have
      autoimmune diseases and brainstem lesions, especially in the area postrema.

PMID- 29055473
TI  - The effect of alcohol and red wine consumption on clinical and MRI outcomes in
      multiple sclerosis.
AB  - BACKGROUND: Alcohol and in particular red wine have both immunomodulatory and
      neuroprotective properties, and may exert an effect on the disease course of
      multiple sclerosis (MS). OBJECTIVE: To assess the association between alcohol and
      red wine consumption and MS course. METHODS: MS patients enrolled in the
      Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and
      Women's Hospital (CLIMB) who completed a self-administered questionnaire about
      their past year drinking habits at a single time point were included in the
      study. Alcohol and red wine consumption were measured as servings/week. The
      primary outcome was the Expanded Disability Status Scale (EDSS) at the time of
      the questionnaire. Secondary clinical outcomes were the Multiple Sclerosis
      Severity Score (MSSS) and number of relapses in the year before the
      questionnaire. Secondary MRI outcomes included brain parenchymal fraction and T2
      hyperintense lesion volume (T2LV). Appropriate regression models were used to
      test the association of alcohol and red wine intake on clinical and MRI outcomes.
      All analyses were controlled for sex, age, body mass index, disease phenotype
      (relapsing vs. progressive), the proportion of time on disease modifying therapy
      during the previous year, smoking exposure, and disease duration. In the models
      for the MRI outcomes, analyses were also adjusted for acquisition protocol.
      RESULTS: 923 patients (74% females, mean age 47 +/- 11 years, mean disease
      duration 14 +/- 9 years) were included in the analysis. Compared to abstainers,
      patients drinking more than 4 drinks per week had a higher likelihood of a lower
      EDSS score (OR, 0.41; p = 0.0001) and lower MSSS (mean difference, - 1.753; p =
      0.002) at the time of the questionnaire. Similarly, patients drinking more than 3
      glasses of red wine per week had greater odds of a lower EDSS (OR, 0.49; p =
      0.0005) and lower MSSS (mean difference, - 0.705; p = 0.0007) compared to
      nondrinkers. However, a faster increase in T2LV was observed in patients
      consuming 1-3 glasses of red wine per week compared to nondrinkers. CONCLUSIONS:
      Higher total alcohol and red wine intake were associated with a lower cross
      sectional level of neurologic disability in MS patients but increased T2LV
      accumulation. Further studies should explore a potential cause-effect
      neuroprotective relationship, as well as the underlying biological mechanisms.

PMID- 29055475
TI  - Neuromyelitis optica spectrum disorder mimicking multiple sclerosis.
AB  - BACKGROUND: MS is a demyelinating CNS disease and has distinct clinical and
      radiological features. Neuromyelitis optica spectrum disorder (NMOSD) is an
      antibody related auto-immune disease known for invalidating episodes of myelitis
      and optic neuritis. OBJECTIVE: Reporting the case of a 29-year old woman with a
      disease course typical for relapsing remitting MS with consistent radiological
      and spinal fluid findings, who developed longitudinally extensive transverse
      myelitis (LETM) with positive aquaporin 4 antibodies, fulfilling the diagnostic
      criteria for NMOSD. METHODS: Case report. RESULTS: LETM is not consistent with
      MS. Consider NMOSD even in patients with typical MS and check for aquaporin-4
      antibodies, with important treatment consequences.

PMID- 29055476
TI  - Prevalence of cognitive impairment among Hungarian patients with relapsing
      remitting multiple sclerosis and clinically isolated syndrome.
AB  - BACKGROUND: Cognitive impairment (CI) is a frequent symptom of multiple sclerosis
      (MS); its prevalence is reported to be 43-70%. It is one of the most important
      determinants of MS patients' quality of life, as it is one of the main factors
      for MS patients becoming unemployed. AIM: We aimed to determine the prevalence of
      CI among the relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS)
      patients in Hungary, to evaluate the predicting factors of CI and to assess the
      differences between sexes and patients with different educational levels.
      PATIENTS AND METHODS: Five-hundred and fifty-three CIS and RRMS patients were
      enrolled to our study from three Hungarian MS centers. Age at screening, age at
      disease onset, disease duration, EDSS score, sex and educational levels were
      analyzed as socio-demographic factors. The BICAMS battery was used to assess
      their cognitive state, the BDI-II battery to assess depression. For statistical
      analysis, we utilized logistical regression, and used Fisher exact tests, chi
      square tests and one-way ANOVA. RESULTS: The mean age of our patients was 44.93
      +/- 11.69 years, mean age at disease onset was 31.95 +/- 10.01 years, the mean
      disease duration was 13.05 +/- 8.05 years and the median EDSS score 2.0 (Range:
      6.5, IQR:2.0) points. Three-hundred and sixteen (57.1%) patients had CI. Sex,
      educational level and EDSS score proved to be significant predictors of CI (OR:
      2.71, p < 0.001; OR: 1.94, p = 0.023; OR: 0.47, p = 0.003 respectively). CI was
      significantly (p < 0.001) more frequent among men (70.1%) than women (52.0%). We
      found, that educational level and EDSS score were only a significant predicting
      factor among women. Thus, the prevalence of CI among women with college or
      university degree was significantly (p < 0.001) less common (39.4%) than women
      with 12-15 years of education (57.4%) and women without a high school degree
      (66.7%). Also, we found that among women with higher EDSS score than 2 points,
      the prevalence of CI is 69.9% as compared to women with EDSS score between 0 and
      2 points, where the prevalence is 42.8% (p < 0.001). No such differences were
      observed among man. DISCUSSION: Our prevalence data is similar to those reported
      in the literature (43-70%), and almost identical to the one assessment using the
      BICAMS battery. We found that men are more vulnerable to CI than women in MS, as
      was reported recently. We are the first to report however, that higher
      educational level and lower EDSS scores are only associated with better cognitive
      performance in women.

PMID- 29055477
TI  - Pregnancy in Multiple Sclerosis: A Portuguese cohort study.
AB  - BACKGROUND: Pregnancy in Multiple Sclerosis (MS) has been a controversial issue,
      without international standardized treatment recommendations. The goal of our
      study was to evaluate the clinical course of MS during pregnancy and the
      respective therapeutic options, obstetrical outcomes and breastfeeding data.
      METHODS: This was a retrospective study including women with a diagnosis of
      relapsing-remitting MS at least one year before pregnancy. Three periods were
      evaluated: one year prior to pregnancy, pregnancy and one year postpartum.
      Information acquired included demographic and disease activity data, treatment
      options, and obstetrical and breastfeeding data. RESULTS: From a cohort of 1134
      patients and 777 women, we included 127 pregnancies in 97 women (111 deliveries
      of a live infant, 11 spontaneous abortions, 3 fetal deaths and 2 voluntary
      abortions). The annualized relapse rate (ARR) decreased during pregnancy, mainly
      in the third trimester (prior to pregnancy 0.6 +/- 0.8 vs. during pregnancy 0.3
      +/- 0.6, p = 0.006). There were no significant changes in the ARR in the year
      after delivery compared to baseline (0.6 +/- 0.8 vs. 0.6 +/- 0.8, p = 0.895).
      Patients with relapses in the postpartum period had a shorter disease duration at
      conception (5.4 +/- 3.9 vs. 7.4 +/- 4.7; p = 0.029) and breastfed less (53.5% vs.
      72.1%, p = 0.046). In the multivariate analysis, relapses during pregnancy
      predicted postpartum relapses (OR = 4.9, p < 0.005). Neither the previous use of
      disease modifying therapy (DMT), given to 80.2% of women, nor breastfeeding,
      caesarean delivery (CD) or epidural analgesia (EA) had an impact on the presence
      of postpartum relapses. Compared to baseline, the Expanded Disability Status
      Scale (EDSS) increased in pregnancy and the postpartum period (1.6 +/- 0.7 vs.
      1.7 +/- 0.9 vs. 2.1 +/- 1.0, p < 0.001). CD was performed in 43.3% of patients,
      mainly because of fetal-pelvic incompatibility (35.7%) and EA was performed in
      63.9%. The most frequent complications were restriction of fetal growth (4.5%)
      and gestational diabetes mellitus (3.6%). Concerning newborns, 6.4% had birth
      asphyxia and 6.1% low birth weight. No malformations were registered. CONCLUSION:
      Despite a reduction in the relapse rate during pregnancy, the presence of
      relapses during pregnancy predicted postpartum relapses, with impact on
      disability. DMT appeared to have no influence on clinical or obstetrical outcome.
      MS did not have a deleterious effect on the pregnancy course. CD and EA were safe
      procedures, with a tendency towards CD in MS patients, compared to Portuguese
      women in general. Breastfeeding did not influence MS activity.

PMID- 29055478
TI  - Predicting falls among patients with multiple sclerosis: Comparison of patient
      reported outcomes and performance-based measures of lower extremity functions.
AB  - BACKGROUND: Accurate fall screening tools are needed to identify those multiple
      sclerosis (MS) patients at high risk of falling. The present study aimed at
      determining the validity of a series of performance-based measures (PBMs) of
      lower extremity functions and patient-reported outcomes (PROs) in predicting
      falls in a sample of MS patients (n = 84), who were ambulatory independent.
      METHODS: Patients were assessed using the following PBMs: timed up and go (TUG),
      timed 25-foot walk (T25FW), cognitive T25FW, 2-min walk (2MW), and cognitive 2MW.
      Moreover, a series of valid and reliable PROs were filled in by participants
      including the activities-specific balance confidence (ABC), 12-item multiple
      sclerosis walking scale (MSWS-12), fall efficacy scale international (FES-I), and
      modified fatigue impact scale (MFIS). The dual task cost (DTC) of 2MW and T25FW
      tests were calculated as a percentage of change in parameters from single to dual
      task conditions. Participants were classified as none-fallers and fallers (?1)
      based on their prospective fall occurrence. RESULTS: In the present study,
      41(49%) participants recorded >= 1 fall and were classified as fallers. The
      results of logistic regression analysis revealed that each individual test,
      except DTC of 2MW and T25FW, significantly predicted future falls. However,
      considering the area under the curves (AUCs), PROs were more accurate compared to
      PBMs. In addition, the results of multiple logistic regression with the first two
      factors extracted from principal component analysis revealed that both factor 1
      (PROs) and factor 2 (PBMs) significantly predicted falls with a greater odds
      ratio (OR) for factor 1 (factor 1: P = <0.0001, OR = 63.41 (6.72-597.90)) than
      factor 2 (P <0.05, OR = 5.03 (1.33-18.99)). CONCLUSIONS: The results of this
      study can be used by clinicians to identify and monitor potential fallers in MS
      patients.

PMID- 29055479
TI  - Is there a change of paradigm towards more effective treatment early in the
      course of apparent high-risk MS?
AB  - BACKGROUND: Aggressive, highly active, or rapidly evolving severe relapsing
      remitting multiple sclerosis (RRMS) is characterized by frequent relapses and
      active disease on magnetic resonance imaging, ultimately leading to a high risk
      for rapid disability accumulation. The treatment approach for high-risk patients
      is evolving into a model of individualized therapy in which early initiation of
      high-efficacy disease-modifying therapy (DMT), which I refer to as "early and
      strong" therapy, is viewed as a rational strategy to prevent the irreversible
      damage that occurs at disease onset and early in the disease course. This
      approach uses an individualized benefit-risk assessment to match the level of DMT
      efficacy with the patient's risk of disease progression and balances it against
      the risk of drug-related adverse events. It also includes consideration of the
      patient's risk tolerance and desire for a high-efficacy treatment. This paper
      discusses the rationale for early treatment, and summarizes the available
      clinical data on high-efficacy and moderately-high efficacy DMTs in patients with
      high-risk RRMS. METHODS: Literature searches were conducted using search terms
      "aggressive RRMS", "highly active RRMS", and "severe RRMS" alone and in
      conjunction with the terms "natalizumab", "fingolimod", "alemtuzumab",
      "mitoxantrone", and "cyclophosphamide". Studies of drug efficacy in these high
      risk populations were reviewed. RESULTS: Subgroup analyses of pivotal trials of
      natalizumab, fingolimod, and alemtuzumab were available, as well as an
      independent study of mitoxantrone and a pilot study of cyclophosphamide. In each
      study, DMT reduced relapses versus either placebo, active comparator, or baseline
      relapse rate. CONCLUSION: Data for the high-efficacy DMTs natalizumab and
      alemtuzumab, and the moderately high-efficacy DMT fingolimod, suggest they are
      effective in this patient population. Further studies are warranted, and clinical
      trial data to inform treatment decisions for this high-risk group represent a
      significant unmet need.

PMID- 29055480
TI  - PER3 VNTR polymorphism in Multiple Sclerosis: A new insight to impact of sleep
      disturbances in MS.
AB  - BACKGROUND: Multiple Sclerosis (MS) is a degenerative disease of central nervous
      system caused by an immune response against the myelin. About half of MS patients
      suffers from sleep disturbances. The circadian clock genes such as PER3 controls
      circadian rhythm and sleep. Due to the role of PER3 in sleep disturbances and
      regulation of immune response, it is possible that PER3 dysregulation increase
      risk of MS disease. METHODS: Study groups included 160 MS patients and 160
      healthy volunteers. PER3 VNTR polymorphism was evaluated by PCR method. The
      genotypic and allelic distribution analyzed by chi square test. RESULTS: There
      was a significant association between genotype PER34/4, and 4-repeat allele with
      MS disease (p = 0.014 and p < 0.001 respectively). The association analysis of
      PER3 VNTR polymorphism with gender status among MS group, and MS onset showed
      that there was a significant correlation between PER34/4 genotype with female
      gender and early onset of MS disease (p = 0.033 and p = 0.028 respectively).
      CONCLUSION: Our data suggest that, PER34/4 genotype may accelerate the course of
      disease in MS susceptible individuals.

PMID- 29055481
TI  - Clinical characteristics and long-term visual outcome of optic neuritis in
      neuromyelitis optica spectrum disorder: A comparison between Thai and American
      Caucasian cohorts.
AB  - BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) occurs more commonly
      in Asian than Caucasian populations. Few studies have examined the clinical
      features and visual outcome of optic neuritis (ON) within NMOSD in different
      racial populations. The objective of this study was to compare the clinical
      characteristics and long-term visual outcome of a Thai and an American-Caucasian
      cohort with NMOSD-related ON. METHODS: Medical records including brain and
      orbital magnetic resonance imaging (MRI) of 16 consecutive subjects who developed
      visual loss due to ON as part of NMOSD evaluated at a single American tertiary
      referral center between 2006 and 2015 were reviewed and compared to those of 16
      consecutive similar subjects evaluated at a single Thai tertiary referral center
      between 2010 and 2016. These cohorts represented the total number of NMOSD
      related ON subjects seen during that time at those institutions. Statistical
      analyses were used for continuous and categorical data sets, and multiple
      regression analysis was used to adjust for differences in duration of follow-up
      and number of episodes of ON in each affected eye. RESULTS: All subjects within
      the Thai cohort were Asian, while the American cohort initially consisted of 14
      Caucasian, 1 Asian and 1 African-American subject, but the latter two were
      excluded from analysis. In the Thai cohort, ON occurred in 21 eyes, with a total
      of 19 episodes, while in the American-Caucasian cohort ON occurred in 22 eyes,
      with a total of 21 episodes. Aquaporin 4 (AQP4)-antibody was positive in all
      subjects except for one American-Caucasian subject. The mean follow-up time was
      17.8 (+/- 16.0) and 52.8 (+/- 51.9) months for the Thai and American-Caucasian
      populations, respectively. There was no difference between the two cohorts with
      respect to gender, age of NMOSD and NMOSD-related ON onset, initial clinical
      presentation of NMOSD, initial visual acuity and automated visual fields,
      prevalence of swollen optic disc in the acute phase, presence of pain on the
      affected side, mean time of onset of ON symptoms to MRI examination, distribution
      of segmental involvement of the anterior visual pathway abnormalities based on
      MRI findings, mean time of onset of ON symptoms to treatment, final visual acuity
      and automated visual fields. However, a higher proportion of Thai affected eyes
      were found to have an initial visual acuity of 20/200 or worse compared with the
      American-Caucasian cohort. Azathioprine was the most common maintenance treatment
      (75%) used among Thai subjects in contrast to rituximab (78.6%) among American
      Caucasian subjects. CONCLUSION: Despite the different prevalence among Thai and
      American-Caucasian populations, the clinical characteristics of ON in the NMOSD
      were very similar across these two populations, other than for more severe visual
      loss initially among Thai subjects. Notably, long-term visual outcome did not
      differ between these cohorts despite significant difference in the maintenance
      treatment regimen. This study did not assess neurological status or outcome.

PMID- 29055482
TI  - A case of acute fulminant multiple sclerosis treated with alemtuzumab.
AB  - We describe the case of a woman who came to our attention for acute onset and
      very rapidly worsening left hemiplegia, vision loss and cognitive impairment.
      MRI, laboratory and clinical investigations were highly suggestive of an active
      inflammatory demyelinating disease. Following exclusion of other possible
      etiologies, a diagnosis of Marburg's variant multiple sclerosis was made. After
      repeated high-dose steroids and plasma-exchange, the patient was treated with a
      first course of alemtuzumab followed by improvement of the clinical and MRI
      picture. This is the first reported case of Marburg type multiple sclerosis
      treated with alemtuzumab.

PMID- 29055483
TI  - A case of lymphoma in a patient on teriflunomide treatment for relapsing multiple
      sclerosis.
AB  - Teriflunomide is an oral therapy approved for relapsing forms of multiple
      sclerosis which has been shown to reduce relapse rate and disability progression.
      We report the case of a 54-year -old black woman with multiple sclerosis who
      developed follicular lymphoma after about 8 months of exposure to teriflunomide.
      Importantly, apart from age, the patient had none of the established risk factors
      for follicular lymphoma. Moreover, although this is the first published case of a
      lymphoma on teriflunomide, it is not the first confirmed case. Ten other cases
      have so far been reported to pharmacovigilance worldwide, and a further 82 with
      leflunomide. In conclusion, an association between teriflunomide and a higher
      risk of lymphoma cannot be ruled out.

PMID- 29055484
TI  - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
      to steroids (CLIPPERS): A pediatric case report with six year follow-up.
AB  - BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular
      enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder
      involving brainstem, pons in particular, characterized by a predominant T-cell
      pathology and responsiveness to glucocorticosteroids. We describe a difficult 6
      year course of this rare syndrome in a 10-year-old girl. CASE REPORT: Our patient
      presented with diplopia, spastic paraparesis, and unsteady gait. MRI showed
      characteristic punctate hyper-intensities with enhancement in the brain stem,
      cerebellar peduncles, and optic chiasm and diffuse nodular enhancement throughout
      the cervical and thoracic spinal cord. Brain biopsy revealed perivascular
      inflammatory lesions compatible with CLIPPERS. Pulse intravenous
      methylprednisolone followed by oral prednisolone resulted in significant clinical
      improvement. She had multiple clinical relapses associated with new brain and/or
      spinal cord lesions despite sequential maintenance methotrexate and rituximab
      with low dose steroids. Each relapse responded to pulse steroids. CONCLUSION: Her
      overall clinical course was progressive but responsive to pulse steroids. Long
      term treatment remains challenging.

PMID- 29055485
TI  - Painful tonic spasm in neuromyelitis optica spectrum disorders: Prevalence,
      clinical implications and treatment options.
AB  - BACKGROUND: Painful tonic spasm (PTS) is a common symptom in patients with
      neuromyelitis optica spectrum disorders (NMOSD). This study aimed to obtain
      further insights into the prevalence, characteristics, and treatment of PTS in
      patients with NMOSD, and to systematically investigate and compare the clinical
      features and prognosis of NMOSD with and without PTS. METHODS: We reviewed the
      medical records and prospectively interviewed patients with NMOSD who attended
      the West China Hospital of Sichuan University in Chengdu, China between September
      2014 and December 2016. RESULTS: In total, 52 of the 230 patients with NMOSD
      experienced PTS (22.61%). Patients with NMOSD and PTS were characterized by a
      higher age at onset (P = 0.017), higher annual relapse rate (ARR) (P = 0.003),
      higher ARR of myelitis (P = 0.011), and a tendency to experience pruritus (P =
      0.025). Sodium channel blocking antiepileptic drugs (carbamazepine or
      oxcarbazepine) had higher efficacy than gabapentin in the treatment of PTS (P =
      0.001). Although the progression index was higher in patients with PTS, this
      difference did not reach statistical significance (P = 0.05). CONCLUSIONS: Our
      study suggested that immunosuppressors for the prevention of relapse should be
      administered without delay in patients with NMOSD and PTS. Owing to the side
      effects of carbamazepine, we recommend oxcarbazepine as the first-line of
      treatment for PTS in patients with NMOSD. Whether PTS is a marker of disease
      severity in NMOSD remains to be determined, requiring a long-term prospective
      observational study.

PMID- 29055486
TI  - Editors' Welcome.

PMID- 29055487
TI  - Outcomes for thoracoscopic versus open repair of small to moderate congenital
      diaphragmatic hernias.
AB  - INTRODUCTION: Indications for thoracoscopic versus open approaches to repair
      congenital diaphragmatic hernia (CDH) are unclear as the variability in defect
      size, disease severity and patient characteristics pose a challenge. Few studies
      use a patient and disease-matched comparison of techniques. We aimed to compare
      the clinical outcomes of open versus thoracoscopic repairs of small to moderate
      sized hernia defects in a low risk population. METHODS: All neonates receiving
      CDH repair of small (type A) and moderate (type B) size defects at an academic
      children's hospital between 2006 and 2016 were retrospectively reviewed and
      analyzed. Patients <36weeks gestation, birth weight <1500g, or requiring
      extracorporeal life support were excluded. Demographics, including CDH severity
      index, and hernia characteristics were recorded. The primary outcome parameter
      was recurrence. Secondary outcomes included length of hospital stay, length of
      mechanical ventilation, time to goal feeds, and mortality. RESULTS: The 51
      patients receiving thoracoscopic (35) and open (16) repairs were similar in
      patient and hernia characteristics, with median 2-year follow-up for both groups.
      Patients with thoracoscopic repair had shorter hospital stay (16 vs. 23days,
      p=0.03), days on ventilator (5 vs. 12, p=0.02), days to start of enteral feeds (5
      vs. 10, p<0.001), and days to goal feeds (11 vs. 20, p=0.006). Higher recurrence
      rates in the thoracoscopic groups (17.1% vs. 6.3%) were not statistically
      significant (p=0.28). Median time to recurrence was 88days for the open repair
      and 183days (IQR 165-218) for the thoracoscopic group. There were no mortalities
      in either group. CONCLUSIONS: In low risk patients born with small to moderate
      size defects, a thoracoscopic approach was associated with decreased hospital
      length of stay, mechanical ventilation days, and time to feeding; however, there
      was a trend towards higher recurrence rates. LEVEL OF EVIDENCE: Level III.

PMID- 29055488
TI  - A multi-institution analysis of predictors of timing of inguinal hernia repair
      among premature infants.
AB  - PURPOSE: Inguinal hernias are common in premature infants, but there is
      substantial variation with regards to timing of repair. We sought to quantify and
      explain this variation. METHODS: Cohort study of infants <34weeks gestation
      diagnosed with an inguinal hernia and discharged from one of 329 neonatal
      intensive units between 1998 and 2012. Multivariable logistic regression
      clustered by site was used to evaluate demographic, clinical, maternal, and
      socioeconomic variables associated with pre-discharge repair. RESULTS: A total of
      8037 infants met study criteria, and 3230 (40%) received a pre-discharge repair.
      The frequency of pre-discharge repair varied by site from 9% to 84%, and
      increased over the study period from 20% in 1998 to 45% in 2012. Concurrent
      gastrostomy or fundoplication and lower socioeconomic status were associated with
      an increased odds of receiving a pre-discharge repair. CONCLUSION: There is
      substantial variation with regards to the timing of repair of inguinal hernias in
      premature infants, with an increasing number of infants receiving repair prior to
      hospital discharge over time. Concurrent gastrostomy or fundoplication and
      socioeconomic status are associated with timing of repair. LEVEL OF EVIDENCE: IV.

PMID- 29055490
TI  - On relationship between patients' month of birth and the prevalence of chronic
      diseases.

PMID- 29055491
TI  - TNF-alpha-308 polymorphism and therapeutic response of ankylosing spondylitis.

PMID- 29055489
TI  - Association between NICE guidance on biologic therapies with rates of hip and
      knee replacement among rheumatoid arthritis patients in England and Wales: An
      interrupted time-series analysis.
AB  - OBJECTIVE: To estimate the impact of NICE approval of tumor necrosis factor
      inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and
      total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England
      and Wales. METHODS: Primary care data [Clinical Practice Research Datalink
      (CPRD)] for the study period (1995-2014) were used to identify incident adult RA
      patients. The age and sex-standardised 5-year incidence of THR and TKR was
      calculated separately for RA patients diagnosed in each six-months between 1995
      2009. We took a natural experimental approach, using segmented linear regression
      to estimate changes in level and trend following the publication of NICE TA 36 in
      March 2002, incorporating a 1-year lag. Regression coefficients were used to
      calculate average change in rates, adjusted for prior level and trend. RESULTS:
      We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and
      TKR surgery, respectively. The modeled average incidence of THR and TKR over the
      biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively,
      with projected (had pre-NICE TA 36 level and trend continued uninterrupted)
      figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was
      associated with a significant average decrease in TKR incidence of -4.41/1000 PYs
      (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no
      effect was seen on THR rates. CONCLUSIONS: Among incident RA patients in England
      and Wales, NICE guidance on TNFi therapies for RA management was temporally
      associated with reduced rates of TKR but not THR.

PMID- 29055492
TI  - Markers of hepatic fibrosis.
AB  - Chronic liver diseases constitute a major health problem. Chronic liver
      inflammation, defined by the degree of hepatic fibrosis, is asymptomatic in a
      significant percentage of patients; hence, the disease often remains undiagnosed
      until it has reached very advanced phases and, frequently, when the damage is
      irreversible. Ideally, patients should be screened during the initial phases of
      chronic inflammation, thus allowing for the effective management of the natural
      evolution of the disease by stopping or delaying its course. Standard diagnostic
      methods (transaminase determination or abdominal ultrasonography) do not allow
      for the early diagnosis of the degree of fibrosis. A liver biopsy is the invasive
      method of choice to screen for fibrosis, however, due to its limitations, non
      invasive diagnostic methods such as elastography or serological markers are
      increasingly used as a good alternative for the early diagnosis of the degree of
      fibrosis.

PMID- 29055493
TI  - Macroion adsorption-electrokinetic and optical methods.
AB  - Recent studies on macroion adsorption at solid/liquid interfaces evaluated by
      electrokinetic and optical methods are reviewed. In the first section a
      description of electrokinetic phenomena at a solid surface is briefly outlined.
      Various methods for determining both static and dynamic properties of the
      electrical double layer, such as the appropriate location of the slip plane, are
      presented. Theoretical approaches are discussed concerning quantitative
      interpretation of streaming potential/current measurements of homogeneous
      macroscopic interfaces. Experimental results are presented, involving
      electrokinetic characteristics of bare surfaces, such as mica, silicon, glass
      etc. obtained from various types of electrokinetic cells. The surface
      conductivity effect on zeta potential is underlined. In the next section, various
      theoretical approaches, proposed to determine a distribution of electrostatic
      potential and flow distribution within macroion layers, are presented.
      Accordingly, the influence of the uniform as well as non-uniform distribution of
      charges within macroion layer, the dissociation degree, and the surface
      conductance on electrokinetic parameters are discussed. The principles, the
      advantages and limits of optical techniques as well as AFM are briefly outlined
      in Section 4. The last section is devoted to the discussion of experimental data
      obtained by streaming potential/current measurements and optical methods, such as
      reflectometry, ellipsometry, surface plasmon resonance (SPR), optical waveguide
      lightmode spectroscopy (OWLS), colloid enhancement, and fluorescence technique,
      for mono- and multilayers of macroions. Results of polycations (PEI, PAMAM
      dendrimers, PAH, PDADMAC) and polyanions (PAA, PSS) adsorption on mica, silicon,
      gold, and PTFE are quantitatively interpreted in terms of theoretical approaches
      postulating the three dimensional charge distribution or the random sequential
      adsorption model (RSA). Macroion bilayer formation, experimentally examined by
      streaming current measurements, and theoretically interpreted in terms of the
      comprehensive formalism is also reviewed. The utility of electrokinetic
      measurements, combined with optical methods, for a precise, in situ
      characteristics of macroion mono- and multilayer formation at solid/liquid
      interfaces is pointed out.

PMID- 29055494
TI  - Suppression of the noise-induced effects in an electrostatic micro-plate using an
      adaptive back-stepping sliding mode control.
AB  - In this work, an adaptive backstepping sliding mode control approach is applied
      through the piezoelectric layer in order to control and to stabilize an
      electrostatic micro-plate. The mathematical model of the system by taking into
      account the small fluctuations in the gap considered as bounded noise is carried
      out. The accuracy of the proposed modal equation is proven using the method of
      lines. By using both approaches, the effects of noise are presented. It is found
      that they lead to pull-in instability as well as to random chaos. A suitable
      backstepping approach to improve the tracking performance is integrated to the
      adaptive sliding mode control in order to eliminate chattering phenomena and
      reinforce the robustness of the system in presence of uncertainties and external
      random disturbances. It is proved that all the variables of the closed-loop
      system are bounded and the system can follow the given reference signals as close
      as possible. Numerical simulations are provided to show the effectiveness of
      proposed controller.

PMID- 29055495
TI  - Cemented K-wire fixation for the treatment of shaft fractures of middle
      phalanges.
AB  - BACKGROUND: The objective of this report is to introduce an external-fixation
      technique using the combination of K-wires and cement. METHODS: From February
      2009 to January 2015, 51 patients with shaft fractures of middle phalanges were
      treated with cemented K-wire fixation. The mean age of patients at surgery was 41
      years. The mean time interval from injury to operation was 6+/-5.78days. Injured
      digits included index (n=18), long (n=15), ring (n=7), and little (n=11) fingers.
      Types of fractures were transversal (n=32), short oblique or spiral (n=5), and
      comminuted (n=14) fractures. Active range of motion of the fingers was measured.
      Total active motion was scored based on the American Society for Surgery of the
      Hand. All measurements were compared with those on the opposite fingers. Patients
      also reported on their satisfaction using the 100-mm visual analogue scale.
      RESULTS: At the final follow-ups of 2 years, range of motion of
      metacarpophalangeal joint, proximal phalangeal joint, and distal interphalangeal
      joint reached 97%+/-2.88, 93%+/-6.65, and 96%+/-3.22 of the opposite fingers,
      respectively. Based on Total active motion scoring system, we obtained 36
      excellent and 15 good results. Based on VAS, patient satisfaction was 96+/-3.44.
      CONCLUSIONS: The cemented K-wire fixation is a reliable technique for the
      treatment of shaft fractures of middle phalanges. The technique is a minimally
      invasive procedure with minimal complications. LEVEL OF EVIDENCE: Therapeutic
      study, Level IVa.

PMID- 29055496
TI  - Bibliometric Indicators of the Status of Clinical Research in Dermatology in
      Spain: Implications for the Future.

PMID- 29055497
TI  - Skin Diseases in the Emergency Department: Impact on Patient Quality of Life.

PMID- 29055498
TI  - Carotid artery stenosis as an independent risk factor for perioperative strokes
      following mitral valve surgical intervention.
AB  - OBJECTIVE: To examine the role of carotid stenosis (CS) and other independent
      risk factors of perioperative stroke following either mitral valve repair or
      replacement. METHODS: Using data from the National Inpatient Sample (NIS)
      database for analysis, all patients who underwent either mitral valve repair or
      replacement were identified using ICD-9 codes. RESULTS: A total of 79,583
      patients who underwent either mitral valve replacement or repair were studied.
      3.39% of the total cohort developed perioperative stroke. With a mean age of
      62.78+/-0.23, there was a statistically significant amount of stroke cases in age
      ranges 65-74 and 75-84 (p<0.05). Risk stratification was done using Van Walraven
      (VWR) scoring and the cohort had a mean of 2.73+/-0.06. The following independent
      predictors were found to be significant: age, female gender, moderate and high
      VWR risk, both symptomatic and asymptomatic CS, atrial fibrillation, previous h/o
      smoking, and other cardiac valve procedures performed, and congestive heart
      failure (CHF). CONCLUSION: CS is a significant risk factor for perioperative
      strokes following mitral valve surgery. Further prospective clinical studies are
      needed that look into risk stratification of patients for better patient
      selection and the question of whether carotid revascularization procedures will
      be beneficial in reducing stroke rates.

PMID- 29055499
TI  - Singing as an adjunct therapy for children and adults with cystic fibrosis: A
      Cochrane review summary.

PMID- 29055500
TI  - Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review.
AB  - PURPOSE: While corticosteroids are relatively inexpensive and commonly used as
      treatment for a variety of conditions, long-term use is known to be associated
      with certain toxicities. Prior systematic reviews have revealed an increased risk
      for costly adverse events (AEs), including bone fracture, infection, and
      gastrointestinal bleeding. The objective of this study was to conduct a
      systematic literature review of recent publications on the burden of long-term
      corticosteroid exposure, specifically, to summarize the AEs and economic impact
      of long-term corticosteroid use and to reveal data gaps for additional research.
      METHODS: The Ovid search platform was used to access scientific literature
      databases. The search strategy targeted the use of corticosteroids and economic
      outcomes research. Articles were restricted to those published between 2007 and
      2016 to cover publications since prior reviews; conference abstracts and articles
      assessing pediatrics were excluded. Titles and abstracts resulting from inclusion
      criteria were screened, and reviewers independently extracted relevant
      information from the relevant full-text articles. FINDINGS: The literature review
      included 32 articles, with 75% focusing on autoimmune diseases, asthma, or lung
      diseases. Included articles were 14 database analyses, 6 simulations, 6 clinical
      trials, 3 systematic literature reviews, 2 patient surveys, and 1 chart review.
      Commonly-cited AEs associated with long-term corticosteroid exposure included
      hypertension (prevalence >30%); bone fracture (21%-30%); cataract (1%-3%);
      nausea, vomiting, and other gastrointestinal conditions (1%-5%); and metabolic
      issues (eg, weight gain, hyperglycemia, and type 2 diabetes; cases had 4-fold the
      risk of controls). Association of dose and duration with increased AE risk is not
      well-quantified. AEs like peptic ulcer and myocardial infarction are particularly
      costly to payers (1-year cost of $21,825 and $26,472, respectively, in year-2009
      USD). The few articles assessing the economic impact of corticosteroid use have
      found dose-related increases in health care resource utilization and costs, with
      per-annum incremental costs relative to nonusers ranging from $5700 in low-dose
      users (<7.5 mg/d) to $29,000 in high-dose users (>15 mg/d). Adherence to
      treatment guidelines on avoiding AEs (eg, prescribing of oral bisphosphonates,
      calcium, and vitamin D) remains low. IMPLICATIONS: Although doses of long-term
      corticosteroids have fallen over the past several decades in response to AEs,
      dose reduction may not be a sufficient solution. Numerous AEs, some very costly,
      persist among long-term corticosteroid users, suggesting a need for further
      research to fill current data gaps, as well as a potential need for alternative
      treatment options.

PMID- 29055501
TI  - Do you feel compelled to work?

PMID- 29055502
TI  - Physician deaths from overwork should arouse greater attention in China.

PMID- 29055504
TI  - Surface characteristics and lesion depth and activity of suspicious occlusal
      carious lesions: Findings from The National Dental Practice-Based Research
      Network.
AB  - BACKGROUND: A lesion on an occlusal tooth surface with no cavitation and no
      radiographic radiolucency but in which caries is suspected owing to surface
      roughness, opacities, or staining can be defined as a suspicious occlusal carious
      lesion (SOCL). The authors' objective was to quantify the characteristics of
      SOCLs and their relationship to lesion depth and activity after these lesions
      were opened surgically. METHODS: Ninety-three dentists participated in the study.
      When a consenting patient had an SOCL, information was recorded about the tooth,
      lesion, treatment provided, and, if the SOCL was opened surgically, its lesion
      depth. The Rao-Scott cluster-adjusted chi2 test was used to evaluate associations
      between lesion depth and color, roughness, patient risk, and luster. RESULTS: The
      authors analyzed 1,593 SOCLs. Lesion color varied from yellow/light brown (40%)
      to dark brown/black (47%), with 13% other colors. Most (69%) of SOCLs had a rough
      surface when examined with an explorer. Over one-third of the SOCLs (39%) were
      treated surgically. Of the 585 surgically treated SOCLs, 61% had dentinal caries.
      There were statistically significant associations between lesion depth and color
      (P = .03), luster (P = .04), and roughness (P = .01). The authors classified 52%
      of the patients as being at elevated caries risk. The authors found no
      significant associations between lesion depth and patient risk (P = .07).
      CONCLUSIONS: Although statistically significant, the clinical characteristics
      studied do not provide accurate guidance for making definitive treatment
      decisions and result in high rates of false positives. PRACTICAL IMPLICATIONS:
      Given that 39% of the opened lesions did not have dentinal caries or were
      inactive, evidence-based preventive management is an appropriate alternative to
      surgical intervention.

PMID- 29055505
TI  - 2017 ACC Expert Consensus Decision Pathway on the Management of Mitral
      Regurgitation: A Report of the American College of Cardiology Task Force on
      Expert Consensus Decision Pathways.
AB  - Mitral regurgitation (MR) is a complex valve lesion that can pose significant
      management challenges for the cardiovascular clinician. This Expert Consensus
      Document emphasizes that recognition of MR should prompt an assessment of its
      etiology, mechanism, and severity, as well as indications for treatment. A
      structured approach to evaluation based on clinical findings, precise
      echocardiographic imaging, and when necessary, adjunctive testing, can help
      clarify decision making. Treatment goals include timely intervention by an
      experienced heart team to prevent left ventricular dysfunction, heart failure,
      reduced quality of life, and premature death.

PMID- 29055506
TI  - The Human Cancer Pathology Atlas: An open-access source for more than 900,000
      Kaplan-Meier plots and 5 million cancer tissue images.

PMID- 29055507
TI  - Corrigendum to "Thaumasiovibrio occultus gen. nov. sp. nov. and Thaumasiovibrio
      subtropicus sp. nov. within the family Vibrionaceae, isolated from coral reef
      seawater off Ishigaki Island, Japan" [Syst. Appl. Microbiol. 40 (5) (2017) 290
      296].

PMID- 29055508
TI  - Distribution of mesotocin-immunoreactive neurons in the brain of the male native
      Thai chicken.
AB  - Mesotocin (MT), a homolog of oxytocin (OT) in mammals, is a nonapeptide
      neurohypophysial hormone that is mainly synthesized in specific neuronal groups
      within the hypothalamus and released from the posterior pituitary gland in
      amphibian, reptilian, and avian species. MT is associated with the neuroendocrine
      regulation of reproductive cycle and maternal behaviors in female native Thai
      chickens. Male birds exhibit parental behaviors as well. However, there are
      limited data regarding the role(s) of the MTergic system in males. Thus, the
      objective of this study was to elucidate the localization of the MT neuronal
      groups in the brain of male native Thai chickens. The distributions of MT
      immunoreactive (-ir) neurons and fibers in the brain were studied utilizing
      immunohistochemistry technique. The results revealed that MT-ir neurons and
      fibers were distributed throughout the brain and extensively in the diencephalon.
      MT-ir neurons and fibers were predominantly located within the nucleus
      supraopticus, pars ventralis (SOv), nucleus preopticus medialis (POM), nucleus
      ventrolateralis thalami (VLT), nucleus paraventricularis magnocellularis (PVN),
      and regio lateralis hypothalami (LHy), suggesting that MT neurons in these nuclei
      might be involved in the reproductive activities and/or parental behavior in the
      male chickens. In addition, the numbers of MT-ir neurons within the SOv and POM
      were significantly higher than those of the VLT, PVN, and LHy. More importantly,
      the number of MT-ir neurons in the SOv was high in the male brain when compared
      with the female brain, indicating that the MTergic system in the SOv might play a
      significant role in male reproductive activities in this equatorial species.

PMID- 29055509
TI  - Are the systemic inflammatory response sindrome valid in the assessment of
      febrile neutropenia?

PMID- 29055510
TI  - Prevalence of Burkholderia cepacia complex species in cystic fibrosis patients in
      Argentina during the period 2011-2015.
AB  - INTRODUCTION: Burkholderia cepacia (B. cepacia) complex is composed of 20
      phylogenetically closely related bacterial species. Some species have emerged as
      opportunistic pathogens in immunocompromised patients and are responsible for
      nosocomial outbreaks. The B. cepacia complex is a recognized respiratory pathogen
      in patients with cystic fibrosis. Burkholderia cenocepacia and Burkholderia
      multivorans (B. multivorans) are the most prevalent species in the world,
      according to the literature. However, research groups in Argentina have described
      a particular local epidemiology, with prevalence of Burkholderia contaminans (B.
      contaminans). METHODS: A total of 68 isolates of B. cepacia complex recovered of
      46 cystic fibrosis patients attended at 14 hospitals distributed in 9 provinces
      of the country were studied. Identification was carried out by conventional
      phenotypic methods and was confirmed by recA gene sequencing. Sequences were
      analysed using the BLASTN program and comparing with B. cepacia complex type
      strains sequences deposited in GenBank. Antibiotic susceptibility tests were
      performed on isolates of the most prevalent species according to CLSI M45
      guidelines. RESULTS: The prevalent specie was B. contaminans (49%, n = 33)
      followed by B. cenocepacia (25%; n = 17). The remaining species were Burkholderia
      seminalis (B. seminalis) (7%, n = 5), B. cepacia (7%, n = 5), B. multivorans (6%,
      n = 4), Burkholderia vietnamensis (5%, n=3) and Burkholderia pyrrocinia (1%; n =
      1). The 46% of B. contaminans isolates were resistant to SXT and 76% sensitive to
      MIN, MEM and CAZ. The isolates of B. cenocepacia were 100% resistant to SXT and
      MIN and 47% to CAZ and MEM. B. seminalis showed high levels of resistance to TMS
      (80%), CAZ (60%) and MIN (60%), and 60% of the isolates showed intermediate
      sensitivity to MEM. CONCLUSION: Previous reports have described the prevalence of
      B. contaminans isolation from cystic fibrosis patients in Argentina, Spain and
      Portugal, and a case of two patients with cystic fibrosis in Ireland has recently
      been reported. Due to the high frequency with which B. contaminans is isolated in
      our country, it is necessary to promote the investigation of possible sources of
      infection and to understand the factors and mechanisms involved in the apparent
      greater transmissibility of this species. Different antimicrobial resistance
      profiles were detected between the species.

PMID- 29055511
TI  - The relationship between causative microorganisms and cardiac lesions caused by
      infective endocarditis: New perspectives from the contemporary cohort of
      patients.
AB  - BACKGROUND: The etiology of infective endocarditis (IE) is changing. More
      aggressive forms with multiple IE cardiac lesions have become more frequent. This
      study sought to explore the relationship between contemporary causative
      microorganisms and IE cardiac lesions and to analyze the impact of multiple
      lesions on treatment choice. METHODS: In 246 patients hospitalized for IE between
      2008 and 2015, cardiac lesions caused by IE were analyzed by echocardiography,
      classified according to the 2015 European Society of Cardiology guidelines and
      correlated with microbiological data. We defined a new parameter, the Echo IE
      Sum, to summarize all IE cardiac lesions in a single patient, enabling
      comprehensive comparisons between different etiologies and treatment strategies.
      RESULTS: Staphylococcus aureus was associated with the development of large
      vegetation (OR 2.442; 95% CI 1.220-4.889; p=0.012), non-HACEK bacteria with large
      vegetation (OR 13.662; 95% CI 2.801-66.639; p=0.001), perivalvular abscess or
      perivalvular pseudoaneurysm (OR 5.283; 95% CI 1.069-26.096; p=0.041), and
      coagulase-negative staphylococci (CoNS) with leaflet abscess or aneurysm (OR
      3.451; 95% CI 1.285-9.266, p=0.014), and perivalvular abscess or perivalvular
      pseudoaneurysm (OR 4.290; 95% CI 1.583-11.627; p=0.004). The Echo IE Sum
      significantly differed between different etiologies (p<0.001), with the highest
      value in non-HACEK and the lowest in streptococcal endocarditis. Patients
      operated for IE had a significantly higher Echo IE Sum vs those who were
      medically treated (p<0.001). CONCLUSION: None of the IE cardiac lesions is
      microorganism-specific. However, more severe lesions were caused by S. aureus,
      CoNS, and non-HACEK bacteria. The highest propensity to develop multiple lesions
      was shown by the non-HACEK group. Higher Echo IE Sum in patients sent to surgery
      emphasized the importance of multiple IE cardiac lesions on treatment choice and
      potential usage of Echo IE Sum in patient management.

PMID- 29055512
TI  - Effect of liquid helium vitrification on cytoskeleton of immature cattle oocytes.
AB  - The developmental potential and the changes in cytoskeleton structures in
      immature oocytes of cattle resulting from liquid helium (LHe) vitrification was
      evaluated in this study. Immature oocytes were randomly divided into three
      groups: fresh oocytes (negative control), oocytes vitrified in liquid nitrogen
      (LN group, positive control), and oocytes vitrified in LHe (LHe group). In
      Experiment 1, the proportions for normal morphology, maturation, cleavage, and
      blastocyst were greater in the LHe group than in the LN group (88.3% compared
      with 79.1%, 51.7% compared with 43.3%, 42.6% compared with 33.0%, and 11.0%
      compared with 4.7%, respectively; P<0.05), and the rates of oocyte development
      were greater in the control group (100%, 72.8%, 64.3%, and 40.3%) than in the
      vitrified groups (P<0.05). In Experiment 2, the effect of vitrification by LHe
      and LN on cytoskeleton of cattle oocytes was examined. The cytoskeleton had
      varying degrees of damage, and the negative influence of LHe vitrification on the
      cytoskeleton was less than that of LN vitrification (P<0.05), and the vitrified
      group had greater cytoskeleton degeneration than the control group (P<0.05). In
      conclusion, LHe vitrification reduced the negative effect of cryoinjury on
      cytoskeleton structure and improved the viability of immature oocytes of cattle
      compared with LN vitrification.

PMID- 29055513
TI  - [A rare familial form of idiopathic pulmonary fibrosis with Poly(A)-specific
      ribonuclease (PARN) mutation].
AB  - New techniques of DNA sequences allow to discover genetics mutations involved in
      familial pulmonary fibrosis. Among them, the PARN (Poly[A]-specific ribonuclease)
      mutation. Herein, we report the case of one patient who has pulmonary fibrosis
      with PARN mutation and the experience of our patient care.

PMID- 29055514
TI  - [About two huge bilateral bronchial atypical carcinoid tumors].
AB  - Carcinoid tumors are well differentiated neuroendocrine tumors of low grade
      malignancy or attenuated malignancy. Atypical bilateral bronchial forms are
      rarely reported. They pose a real problem of therapeutic strategy. We report a
      case of a 36-year-old woman with two large bilateral atypical carcinoid tumors.
      She received delayed bilateral parenchymal resection with postoperative
      uneventful course. Through a review of the literature, we discuss the therapeutic
      strategy. This observation remains special for several reasons. Not only by the
      rarity of the bilateral and atypical forms but also for the bilateral tumor sizes
      which led to a difficult intraoperative anesthetic management.

PMID- 29055515
TI  - Creating an environment of empowerment in the intensive care units: From
      containment to mobilisation.

PMID- 29055516
TI  - Should intensive care admission be restricted to the most severely ill patients?

PMID- 29055517
TI  - Enhanced CD8+ cytolytic T cell responses in the peripheral circulation of
      patients with sarcoidosis and non-Lofgren's disease.
AB  - BACKGROUND: The role of CD4+ T cells in the immunopathogenesis of pulmonary
      sarcoidosis is well-established, while less is known about the phenotype and
      function of CD8+ cytolytic T cells (CTLs). METHODS: CD8+ CTLs were explored in
      peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25
      patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was
      assessed by the expression of cytolytic effector molecules perforin, granzyme B
      and granulysin in CD8+ T cells, using flow cytometry. Cytolytic function in blood
      lymphocytes was assessed using a standard 51Cr-release assay. Patients with
      Lofgren's syndrome (LS) and an acute disease onset, were compared to non-LS
      patients with an insidious onset. RESULTS: Higher proportions of peripheral CD8+
      CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to
      healthy controls. Blood CTLs from non-LS patients had significantly higher
      expression of perforin, granzyme B and granulysin compared to matched BAL, while
      LS patients maintained lower levels of effector molecules in both compartments.
      Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly
      from the non-LS group, showed a higher target cell lysis compared to controls.
      CONCLUSION: These results demonstrated enhanced peripheral CD8+ CTL responses in
      sarcoidosis, especially in non-LS patients who have an increased risk of chronic
      disease. Further comprehensive clinical studies are warranted to increase our
      understanding of CD8+ CTL responses in sarcoidosis.

PMID- 29055518
TI  - The prognostic effect of salvage surgery and radiotherapy in patients with
      recurrent primary urethral carcinoma.
AB  - BACKGROUND: To evaluate the impact of salvage therapy (ST) on overall survival
      (OS) in recurrent primary urethral cancer (PUC). PATIENTS: A series of 139
      patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were
      diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of
      ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier
      analysis with log-rank was used to estimate the impact of ST on OS (median follow
      up = 21, interquartile range: 5-48). RESULTS: The 3-year OS for patients free of
      any recurrence (I), with solitary or concomitant urethral recurrence (II), and
      nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002
      for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with
      recurrences, the modality of primary treatment of recurrence was salvage surgery
      in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus
      RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In
      patients with recurrences, those who underwent salvage surgery or RT-based ST had
      similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%,
      P = 0.65), and exhibited superior 3-year OS compared to patients who did not
      undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P =
      0.29 for surgery vs. RT-based ST). CONCLUSIONS: In this study, patients who
      underwent ST for recurrent PUC demonstrated improved OS compared to those who did
      not receive ST and exhibited similar survival to those who never developed
      recurrence after primary treatment.

PMID- 29055519
TI  - Good, better, best? A comprehensive comparison of healthcare providers'
      performance: An application to physiotherapy practices in primary care.
AB  - Most payment methods in healthcare stimulate volume-driven care, rather than
      value-driven care. Value-based payment methods such as Pay-For-Performance have
      the potential to reduce costs and improve quality of care. Ideally, outcome
      indicators are used in the assessment of providers' performance. The aim of this
      paper is to describe the feasibility of assessing and comparing the performances
      of providers using a comprehensive set of quality and cost data. We had access to
      unique and extensive datasets containing individual data on PROMs, PREMs and
      costs of physiotherapy practices in Dutch primary care. We merged these datasets
      at the patient-level and compared the performances of these practices using case
      mix corrected linear regression models. Several significant differences in
      performance were detected between practices. These results can be used by both
      physiotherapists, to improve treatment given, and insurers to support their
      purchasing decisions. The study demonstrates that it is feasible to compare the
      performance of providers using PROMs and PREMs. However, it would take an extra
      effort to increase usefulness and it remains unclear under which conditions this
      effort is cost-effective. Healthcare providers need to be aware of the added
      value of registering outcomes to improve their quality. Insurers need to
      facilitate this by designing value-based contracts with the right incentives.
      Only then can payment methods contribute to value-based healthcare and increase
      value for patients.

PMID- 29055521
TI  - Mortality during heatwaves 2003-2015 in Frankfurt-Main - the 2003 heatwave and
      its implications.
AB  - Heatwaves have always occurred, but they are expected to intensify in frequency,
      duration and intensity due to climate change. Germany (like most European
      countries) experienced a distinct heatwave in 2003. Afterwards local heat health
      action plans (HHAP) were implemented in numerous regions (for example in Hesse).
      This analysis was designed to compare the heat wave of 2003 with the following
      ones in 2006, 2010 and 2015. We discuss whether measures from the Hessian HHAP
      were effective in reducing mortality and identify specific characteristics of the
      2003 heatwave which did not allow direct comparison. Mortality and temperature
      data from the city of Frankfurt collected between 2003 and 2015 was used to
      answer the question of whether the implemented HHAP were effective, or if the
      mortality in 2003, pre-HHAP implementation, was especially high due to other
      factors. Excess mortality in 2003 was considerably higher for the overall
      population than in the heatwaves of the following years (2003: 77.8%, 2006: 12%,
      2010: 22.7%, 2015: 38.1%). Heatwaves did not result in a significant excess
      mortality at all in some years, e.g. in 2006. Aside from the mortality rate, the
      duration of the heatwave (2003: 12days; 2006: 5days; 2010: 5days; 2015: 5days)
      was the only differing characteristic, leading to the hypothesis that heatwave
      duration might be a better indicator of mortality during heatwaves, than other
      characteristics, alone or combined. In summary regarding the effectiveness of the
      HHAP remains inconclusive since the pre-HHAP heatwave of 2003 differed in certain
      characteristics (especially the longer duration). Furthermore, the activities
      representing the HHAP were diverse and were implemented stepwise over some years.
      The effects on mortality of individual activities cannot be evaluated. Further
      research should consider differences, e.g. between places (climate zones etc.)
      and heatwave definitions.

PMID- 29055520
TI  - Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in
      children in the HOME Study.
AB  - Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to
      impair executive function in children, but little is known whether childhood PBDE
      exposures play a role. Using the Health Outcomes and Measures of the Environment
      (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we
      investigated the association between repeated measures of PBDEs during childhood
      and executive function at 8 years in 208 children and whether effect modification
      by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8
      years to measure PBDEs. The Behavior Rating Inventory of Executive Function was
      completed by parents to assess executive function at 8 years. We used multiple
      informant models to examine childhood PBDEs during several exposure windows. Null
      associations were observed between early childhood PBDEs and executive function.
      However, we observed significant adverse associations between a 10-fold increase
      in concurrent concentrations of BDE-28 (beta=4.6, 95% CI 0.5, 8.7) and BDE-153
      (beta=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8
      years were significantly associated with poorer emotional and impulse control. No
      associations were noted between childhood PBDEs and metacognition or global
      executive function. However, child sex significantly modified the associations,
      with significantly poorer executive function among males with higher concurrent
      BDE-153, and null associations in females. Our study findings suggest that
      concurrent PBDE exposures during childhood may be associated with poorer
      executive function, specifically behavior regulation. Males may also be more
      sensitive to adverse associations of concurrent PBDEs on executive function.

PMID- 29055522
TI  - Tailoring Water, Sanitation, and Hygiene (WASH) Targets for Soil-Transmitted
      Helminthiasis and Schistosomiasis Control.
AB  - The World Health Organization's (WHO) 2015-2020 Global Strategy on water,
      sanitation, and hygiene (WASH) and neglected tropical diseases (NTDs) encourages
      integration, whilst maintaining existing structured NTD investments, and
      acceleration towards Sustainable Development Goal (SDG) targets. Accordingly, SDG
      associated and WASH-NTD indicators have been developed, commencing important
      intersectoral dialogue, alongside opportunities for future disease-specific
      refinements. The rationale for soil-transmitted helminthiasis (STH)- and
      schistosomiasis-specific WASH considerations, and a traffic-light figure, are
      presented here to indicate where current international definitions may, or may
      not, suffice. Certain unique aspects in control dynamics and parasitic
      lifecycles, however, necessitate additional implementation research with more
      appropriate measurement indicators developed to record programmatic interventions
      and to define strategic priorities more effectively.

PMID- 29055523
TI  - [Severe head injury in Spain].

PMID- 29055524
TI  - [Role of surgery in spontaneous spondylodiscitis: Experience in 83 consecutive
      patients].
AB  - OBJECTIVE: To describe and discuss the role of surgery in the management of
      spontaneous spondylodiscitis. PATIENTS AND METHODS: Retrospective review on the
      outcome and complications of a cohort of patients undergoing surgery for
      spontaneous (non-postoperative) spondylodiscitis of any spinal level or
      aetiology. RESULTS: From 1995 to 2014, 83 patients (45% females, median age 66)
      with spondylodiscitis were treated. Microbiological confirmation was obtained in
      67.4%. Forty-four percent of patients presented with neurological defect. The
      most common affected level was thoracic (54.2%). The most frequent isolations
      were Mycobacterium tuberculosis (229%), Staphylococcus aureus (20.5%) and MRSA
      (7.2%). Eighty-one patients underwent surgery: simple laminectomy and/or biopsy
      (22.2%), debridement and posterior fixation (43.2%) and debridement and anterior
      fixation (34.5%). Improvement of pain or neurological defect was achieved in
      86.7% of the patients; 7 patients stabilized and 2 worsened. Complications
      occurred in 35 patients, mainly pleural effusion (9), anaemia (7) and need for re
      debridement (7). Median postoperative stay was 14days. After a median follow up
      of 8.5 months, 46 patients were considered completely cured, 10 presented
      sequelae, 22 patients were lost and 5 patients died. No readmissions occurred
      because of the infectious episode. CONCLUSIONS: Although prolonged and specific
      antibiotic therapy remains the mainstay of treatment in spontaneous
      spondylodiscitis, surgery provides samples for microbiological confirmation and
      histopathologic study, allows debridement of the infectious foci and stabilizes
      the spine. In our experience, the use of internal metallic fixation material
      accelerates recovery and does not predispose to chronic infection.

PMID- 29055525
TI  - Development of immunosorbents coupled on-line to immobilized pepsin reactor and
      micro liquid chromatography-tandem mass spectrometry for analysis of
      butyrylcholinesterase in human plasma.
AB  - Human butyrylcholinesterase (HuBuChE) has been widely used as a biomarker of
      exposure to organophosphorus (OPs) warfare agents. Indeed, intoxication by OPs
      can be proven by LC-MS/MS analysis of a specific HuBuChE nonapeptide on which OPs
      covalently bind. Therefore, we developed a fast, selective and sensitive on-line
      set-up for the analysis of HuBuChE from plasma that combines immunoextraction by
      anti-HuBuChE antibodies, pepsin digestion on Immobilized Enzyme Reactors (IMER)
      and microLC-MS/MS analysis of the target nonapeptide, FGESAGAAS. Two pepsin-based
      IMERs were prepared and characterized in terms of grafting and digestion yields
      and were coupled on-line to microLC-MS/MS analysis. In addition, immunosorbents
      were prepared by covalent grafting of three anti-HuBuChE antibodies on CNBr
      sepharose and epoxy-polymethacrylate supports and packed in precolumns. The best
      antibody grafting yields were obtained with sepharose-based supports, with
      grafting yields up to 98%. B2 18-5 monoclonal antibody grafted on sepharose led
      to the best immunosorbent, with HuBuChE recovery close to 100%. The immunosorbent
      was introduced upstream of the on-line digestion set-up and immunoextraction of
      HuBuChE was achieved in 14min while digestion was performed in 20min, allowing
      detection of the target nonapeptide in less than 1h. The global recovery of the
      nonapeptide was higher than 42% using the best immunosorbent with a RSD value
      lower than 7% (n=3). Finally, the limit of quantification evaluated in plasma
      sample was 2fmol of nonapeptide. This value, corresponding to 0.5fmol of HuBuChE
      tetramer, is well below the average amount of HuBuChE tetramer in 50MUL of plasma
      (590fmol).

PMID- 29055526
TI  - Online analysis of five organic ultraviolet filters in environmental water
      samples using magnetism-enhanced monolith-based in-tube solid phase
      microextraction coupled with high-performance liquid chromatography.
AB  - Due to the endocrine disrupting properties, organic UV filters have been a great
      risk for humans and other organisms. Therefore, development of accurate and
      effective analytical methods is needed for the determination of UV filters in
      environmental waters. In this work, a fast, sensitive and environmentally
      friendly method combining magnetism-enhanced monolith-based in-tube solid phase
      microextraction with high-performance liquid chromatography with diode array
      detection (DAD) (ME-MB-IT/SPME-HPLC-DAD) for the online analysis of five organic
      UV filters in environmental water samples was developed. To extract UV filters
      effectively, an ionic liquid-based monolithic capillary column doped with
      magnetic nanoparticles was prepared by in-situ polymerization and used as
      extraction medium of online ME-MB-IT/SPME-HPLC-DAD system. Several extraction
      conditions including the intensity of magnetic field, sampling and desorption
      flow rate, volume of sample and desorption solvent, pH value and ionic strength
      of sample matrix were optimized thoroughly. Under the optimized conditions, the
      extraction efficiencies for five organic UV filters were in the range of 44.0
      100%. The limits of detection (S/N=3) and limits of quantification (S/N=10) were
      0.04-0.26MUg/L and 0.12-0.87MUg/L, respectively. The precisions indicated by
      relative standard deviations (RSDs) were less than 10% for both intra- and inter
      day variabilities. Finally, the developed method was successfully applied to the
      determination of UV filters in three environmental water samples and satisfactory
      results were obtained.

PMID- 29055527
TI  - Multi-state steric mass action model and case study on complex high loading
      behavior of mAb on ion exchange tentacle resin.
AB  - Tentacle resins for IEX are increasingly applied in preparative chromatography
      for their higher selectivity and higher capacities in comparison to IEX resins
      without tentacles. However, tentacle resins are often observed to cause unusual
      elution behavior of monoclonal antibodies under high loading conditions.
      Understanding this elution behavior is important for a quality by design
      approach, as it is now mandated by regulatory agencies. A model-based analysis of
      load, wash and gradient elution is performed for a monoclonal antibody (mAb) on
      Fractogel SO3-. Four experiments with increasing loaded mass show complex peak
      shapes and formation of a shoulder under overloaded conditions. We hypothesize
      that the observed peak shapes are caused by mAbs binding in multiple states on
      the tentacle ion-exchange resin. A new multi-state SMA binding model is used for
      testing this hypothesis. A two-state binding model is found to quantitatively
      reproduce all four experiments. An in-depth analysis reveals that the shoulder
      formation under overloaded conditions can be explained by multi-state binding
      that particularly manifests in rapid but weak re-adsorption of eluting molecules
      near the column end. The introduced multi-state SMA model combines features of
      the so-called spreading model (multiple bound states) and of the standard SMA
      model (salt dependency). It is by no means limited to ion-exchange chromatography
      on tentacle resins, but the same concept can be applied for studying systems that
      are based on other physical mechanisms. The new model can potentially improve
      mechanistic understanding and facilitate quantitative simulation of various
      phenomena, such as caused by reorientation, reconformation or unfolding of bound
      species. Similar concepts can be applied for studying surface-induced aggregation
      and denaturation.

PMID- 29055528
TI  - Development of an on-line solid phase extraction ultra-high-performance liquid
      chromatography technique coupled to tandem mass spectrometry for quantification
      of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic
      investigations.
AB  - Regulatory measures and public concerns regarding bisphenol A (BPA) have led to
      its replacement by structural analogues, such as Bisphenol S (BPS), in consumer
      products. At present, no toxicokinetic investigations have been conducted to
      assess the factors determining human internal exposure to BPS for subsequent risk
      assessment. Toxicokinetic studies require reliable analytical methods to measure
      the plasma concentrations of BPS and its main conjugated metabolite, BPS
      glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the
      simultaneous quantification of BPS and BPS-G in ovine plasma was therefore
      developed and validated in accordance with the European Medicines Agency
      guidelines for bioanalytical method validation. This method has a limit of
      quantification of 3ngmL-1 for BPS and 10ngmL-1 for BPS-G, an analytical capacity
      of 200 samples per day, and is particularly well suited to toxicokinetic studies.
      Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA,
      is efficiently metabolized into its glucuronide form. However, the clearances and
      distributions of BPS and BPS-G were lower than those of the corresponding
      unconjugated and glucuroconjugated forms of BPA.

PMID- 29055530
TI  - Biorefinery integration of microalgae production into cassava processing
      industry: Potential and perspectives.
AB  - Cassava, the 5th most important staple crop, generates at least 600L of
      wastewater per ton of processed root. This residue, cassava processing wastewater
      (CPW) has a high chemical oxygen demand, that can reach 56 g/L, and has also high
      concentrations of several mineral nutrients. The cultivation of microalgae such
      as Chlorella, Spirulina and wild strains was evaluated in the last years in raw,
      minimally processed and partially digested CPW. Concentrations of 2-4 g/L of
      these microalgae, comparable to those obtained in synthetic media, could be
      reached. The BOD of the residue was reduced by up to 92%. This process can be
      integrated into cassava processing industries, if challenges such as the toxicity
      of the concentrated residue, bacterial contamination, and the isolation of robust
      strains are addressed. Because CPW carries about 11% of the crop energy,
      integrating biogas production and microalgal cultivation into the cassava
      processing chain is promising.

PMID- 29055529
TI  - Oxidation, glycation and glycoxidation-The vicious cycle and lung cancer.
AB  - The combine effect of oxidative and glycative stress predisposed to
      glycoxidation, and their outcomes that play critical role in lung cancer have
      been examined in different ways. The therapeutic approaches for lung cancer are
      still unsatisfactory. We observe some unclear and decisive pathways which might
      play an important role in targeting lung cancer. The roadmap of signaling pathway
      includes p38 MAPK, NF-kB, TNF-alpha and AGE-RAGE binding affinity play role in
      the cell growth, proliferation, apoptosis inhibition and metastasis. The goal of
      this review is to achieve a new signaling map inside the lung cancer which is
      mediated by glycoxidative products mainly reactive dicarbonyls and advanced
      glycation end products (AGEs). Additionally, AGE-RAGE binding critically
      regulates the suppression and promotion of lung cancer via inhibition and
      activation of different signaling pathways. Hence, this review suggests the role
      of oxidation, glycation, and glycoxidation in lung cancer.

PMID- 29055531
TI  - The utility of the FIPI score in predicting long-term clinical outcomes in
      patients with Fabry disease receiving enzyme replacement therapy with agalsidase
      alfa.
AB  - Fabry disease is a rare X-linked lysosomal storage disorder in which there is
      deficiency of alpha galactosidase A. Enzyme replacement therapy (ERT) is
      commercially available and has been demonstrated to improve cardiac and renal
      outcomes. Predictive scores, such as the Fabry International Prognostic Index
      (FIPI), have been developed to stratify disease severity; however, these have not
      been validated to predict outcomes in patients receiving ERT. We show that the
      FIPI score at baseline can predict outcomes in a group of patients on long-term
      ERT.

PMID- 29055532
TI  - Dairy producers' attitudes toward reproductive management and performance on
      Canadian dairy farms.
AB  - The objectives of this study were to explore Canadian dairy producers' attitudes
      toward reproductive performance and challenges they perceive to be related to
      reproduction and reproductive management practices. A survey in both English and
      French was developed, validated, and administered to Canadian dairy farmers
      between March and May 2014 to collect general farm, reproduction management, and
      reproductive performance data, as well as opinions and perceptions about
      different facets of reproduction. Associations between management practices and
      the perceived importance of reproduction were tested using a logistic regression
      model. Thematic network analysis was used to identify themes from the open-ended
      survey questions about challenges concerning reproduction. Finally, questions
      that were answered on a Likert scale were graphically represented using diverging
      stacked bar charts. A total of 832 questionnaires were completed online and by
      mail, which represents approximately 7% of all dairy farms in Canada. Respondents
      that ranked reproduction in lactating dairy cows as 1 of the 3 most important
      challenges faced on their farm (66%) were more likely to house their lactating
      cows in a tiestall and to have a lower herd annual 21-d pregnancy rate. Estrus
      detection and conception risk were 2 major themes raised and discussed by the
      respondents. Other concepts, including housing and milk production, were also
      perceived to affect estrus detection and conception risk. Whereas analysis of
      open-ended survey questions does not allow for quantification of the importance
      of different themes in the sample as a whole, it does show that respondents are
      aware of the multifactorial complexity of reproductive challenges on dairy farms.
      Improving performance was the main factor influencing decisions concerning
      reproduction for 80% of the respondents, and they adopted tools and technologies
      such as synchronization programs and automated activity monitoring systems to
      improve herd reproductive performance. More research is required to describe how
      this performance is defined and perceived by the respondents, and how it relates
      to the actual variability of performance (i.e., pregnancy rate) among farms.

PMID- 29055534
TI  - Association of rumination time and health status with milk yield and composition
      in early-lactation dairy cows.
AB  - The objective of this study was to determine the associations of rumination time
      (RT) and health status with milk yield and milk composition. This study used 339
      dairy cows from 4 commercial dairy farms in Ontario, Canada (first lactation, n =
      107; second lactation, n = 112; >=third lactation, n = 120). Rumination time was
      monitored (24 h/d) using an automated system from 1 to 28 d in milk (DIM). Cows
      were milked 3*/d on each farm, and 2 farms recorded milk weights at each milking
      to determine daily milk yield (n = 170). Cows were also monitored for milk
      composition (fat and protein content) 1*/wk. Last, subclinical ketosis (SCK) was
      diagnosed 1*/wk; cows with at least one blood sample with beta-hydroxybutyrate
      >=1.2 mmol/L postcalving were diagnosed with SCK. Cases of retained placenta,
      metritis, milk fever, or mastitis during the study period were also recorded.
      Cows were categorized into 1 of 4 groups: healthy cows that had no SCK or any
      other health issue (HLT; n = 139); cows that were treated for at least one health
      issue other than SCK (HLT+; n = 50); SCK cows with no other health problems
      during transition (HYK; n = 97); or cows that had SCK and one or more other
      health problems (HYK+; n = 53). All data were summarized by week across cows, and
      the associations between rumination time and milk yield (n = 170) and milk
      composition (n = 339) were modeled. Across all lactations, and including all
      health categories, milk yield increased by week, whereas fat and protein content
      both decreased by week. A positive association was found between summarized RT
      and milk yield in first-lactation (+0.006 +/- 0.003 kg/min of RT) and second
      lactation (+0.015 +/- 0.004 kg/min of RT) cows from 4 to 28 DIM, as well as in
      >=third-lactation cows; however, the relationship between RT and milk yield
      differed across weeks in those cows. A negative association between RT and milk
      fat content was found in >=third-lactation cows (-0.002 +/- 0.00059 percentage
      points/min of RT). From 4 to 28 DIM, >=third-lactation HYK and HYK+ cows produced
      less protein (0.11 +/- 0.051 and 0.13 +/- 0.056 percentage points, respectively)
      than HLT cows. Over the 4-wk observation period, first-lactation HYK+ cows tended
      to deposit 0.11 +/- 0.056 percentage points less protein in their milk compared
      with HLT cows. Second-lactation HYK+ cows produced less milk than HLT cows each
      week during early lactation. In summary, RT was positively associated with milk
      yield in early-lactation dairy cows, across all lactations, and negatively
      associated with milk fat content in >=third-lactation cows. Further, the results
      showed that early-lactation cows that experience SCK, particularly with one or
      more other health problems, might have decreased milk yield and milk protein
      content.

PMID- 29055533
TI  - Short communication: Genomic and phenotypic analyses of exopolysaccharides
      produced by Streptococcus thermophilus KLDS SM.
AB  - Streptococcus thermophilus plays important roles in the dairy industry.
      Streptococcus thermophilus KLDS SM could produce a high amount of
      exopolysaccharides (EPS). To understand the possible link between the genotype
      and the phenotype regarding EPS, the complete genome of S. thermophilus KLDS SM
      was sequenced and investigated in silico for genes related to carbohydrate
      fermentation, nucleotide sugars synthesis, and EPS gene cluster. We found that S.
      thermophilus KLDS SM is able to ferment sucrose, mannose, glucose, galactose, and
      lactose from the genomic research, which was confirmed by API 50 CH (bioMerieux,
      Marcy l'Etoile, France). The genetic analysis of nucleotide sugars and EPS
      cluster revealed that the EPS produced by this strain are composed of galactose
      and glucose, in accordance with the biochemical result. Furthermore, differences
      in the molecular mass of EPS from S. thermophilus KLDS SM cultivated under
      different carbon sources were correlated with the transcription levels of the
      genes encoding chain length determination protein and glycosyltransferase. Our
      findings provide a better understanding of the link between the genetic elements
      and the chemical conformation of EPS and a theoretical basis for producing tailor
      made EPS through genetic and metabolic engineering approaches.

PMID- 29055535
TI  - Short communication: The first report of Cyberlindnera rhodanensis associated
      with clinical bovine mastitis.
AB  - An acute case of clinical mastitis in a Holstein cow from second lactation is
      reported here. A milk sample from the affected quarter was cultured on 5% bovine
      blood agar and incubated at 37 degrees C for 72 h. After 24 h of incubation,
      numerous colonies of yeast were observed: the Candida characteristic was not
      detected by CHROMagar Candida (Difco, Franklin Lakes, NJ). The DNA extraction of
      the isolate was performed, and DNA was subjected to amplification and sequencing
      of the D1/D2 region of the large subunit rRNA gene. The sequences were aligned
      using Mega 7.0 and used for searching GenBank by BLASTn (Basic Local Alignment
      Search Tool for nucleotides), revealing 98% of identity with Cyberlindnera
      rhodanensis. To date, this is the first report of this yeast associated with
      clinical bovine mastitis.

PMID- 29055536
TI  - Symposium review: Structure-function relationships in cheese.
AB  - The quality and commercial value of cheese are primarily determined by its
      physico-chemical properties (e.g., melt, stretch, flow, and color), specific
      sensory attributes (e.g., flavor, texture, and mouthfeel), usage characteristics
      (e.g., convenience), and nutritional properties (e.g., nutrient profile,
      bioavailability, and digestibility). Many of these functionalities are determined
      by cheese structure, requiring an appropriate understanding of the relationships
      between structure and functionality to design bespoke functionalities. This
      review provides an overview of a broad range of functional properties of cheese
      and how they are influenced by the structural organization of cheese components
      and their interactions, as well as how they are influenced by environmental
      factors (e.g., pH and temperature).

PMID- 29055537
TI  - Mitigation of variability between competitively fed dairy cows through increased
      feed delivery frequency.
AB  - The objective of this study was to determine whether increased frequency of total
      mixed ration (TMR) delivery could mitigate the effects of feed bunk competition
      on the behavior and productivity of individual lactating dairy cows within a
      group. We hypothesized that, for competitively fed cows, a greater frequency of
      TMR delivery would improve access to feed, and reduce individual variability in
      behavior, meal patterns, and production between cows. Sixteen lactating Holstein
      dairy cows (first lactation = 4, second lactation = 5, >= third lactation = 7)
      averaging 72 +/- 35 d in milk and producing 42 +/- 6 kg of milk/d at the start of
      the trial, were categorized as either young (<= second lactation) or mature (>=
      third lactation) and paired to maximize difference in parity. Pairs were housed 4
      at a time and competitively fed a TMR at a ratio of 2 cows:1 feed bin. Cow pairs
      were exposed, in a crossover design, to each of 2 feed delivery frequency
      treatments: low (2*/d) and high (6*/d) frequency. Treatments were applied for 10
      d, with dry matter intake (DMI), feeding behavior (feeding time, feeding rate,
      and meal patterns), and replacement frequency for each cow recorded using an
      automated feed intake system on d 6 to 10 of each period. Rumination time, feed
      sorting, lying behavior, and productivity were also measured for this period.
      Variability in behavior within pairs of cows was determined by averaging the
      absolute difference within each pair over the recording period to provide 1 value
      per pair. Frequency of TMR delivery did not affect feeding time, feeding rate,
      DMI, replacement frequency, feed sorting, or productivity. At the high delivery
      frequency, there was a tendency for rumination time to increase [low = 519.3;
      high = 544.3 min/d; standard error of the difference (SED) = 11.32], and to be
      more variable within pairs (low = 38.0, high = 50.0 min/d; SED = 5.57). Cows also
      had longer lying bouts at the high delivery frequency (low = 53.0; high = 55.5
      min/bout; SED = 1.00). No differences in daily meal patterns were found between
      treatments; however, the average first meal following each feeding indicated that
      cows under the high delivery frequency spent less time, consuming smaller meals
      during peak feeding periods. Comparing the young and mature individuals within
      each treatment pair revealed that feeding rate (young = 0.16; mature = 0.19
      kg/min; SED = 0.014) and DMI (young = 25.6; mature = 28.6 kg of DM/d; SED = 1.36)
      were lower for the young cows on both treatments. Meal frequency was greater in
      young cows (young = 9.0; mature = 7.5 meals/d; SED = 0.71) and meal size was
      greater in mature cows (young = 3.2; mature = 4.2 kg of DM/meal; SED = 0.32)
      across treatments. These results suggest that for cows fed at a high level of
      competition, increasing TMR delivery frequency from 2 to 6*/d led to consumption
      of shorter, smaller meals during peak periods of feed consumption. However, under
      these conditions, the relative parity of competitively fed cows had a greater
      effect on feeding behavior, meal patterns, and production than did the frequency
      of feed delivery.

PMID- 29055538
TI  - Effects of feeding unlimited amounts of milk replacer for the first 5 weeks of
      age on rumen and small intestinal growth and development in dairy calves.
AB  - The development of the gastrointestinal tract in newborn calves is essential for
      sufficient nutrient uptake. An intensive milk feeding during the neonatal period
      may impair the rumen development in calves. The aim of this study was to
      investigate effects of milk replacer (MR) feeding in unlimited amounts for the
      first 5 wk of age on the gastrointestinal growth and development in preruminant
      calves at wk 9 of age. Twenty-eight newborn Holstein and Holstein * Charolais
      crossbred calves (19 male and 9 female) were fed MR ad libitum (ADLIB) or in
      restricted amounts (6 L per day; RES) until wk 5 of age. Thereafter, the MR
      intake of ADLIB was gradually reduced at wk 6 and 7, and all calves received 6 L
      of MR per day until wk 9 of age. In wk 9, calves were slaughtered and carcass and
      organ weight as well as rumen papilla size in the atrium, ventral sac, and
      ventral blind sac, and villus size of the mucosa in the small intestine
      (duodenum; proximal, mid, and distal jejunum; and ileum) were determined. The
      expression of mRNA associated with the local insulin-like growth factor (IGF)
      system was measured in the rumen epithelium. Ad libitum MR feeding increased MR
      intake and growth in ADLIB without influencing concentrate intake compared with
      RES. Carcass weight in wk 9 was greater in ADLIB than in RES. The density of the
      rumen papillae in the atrium and ventral blind sac was greater in RES than in
      ADLIB calves, but surface area of the epithelium was not different between groups
      in the investigated regions of the rumen. The mRNA abundance of IGF1 in the
      atrium tended to be greater and the IGFR1 mRNA abundance in the ventral sac
      tended to be lower in the ADLIB than in the RES feeding group. The rumen pH and
      volatile fatty acid concentrations were not affected by MR feeding intensity. In
      mid-jejunum, villus circumference was greater in ADLIB than in RES calves. In the
      distal jejunum, villus surface area and the villus height/crypt depth ratio were
      greater and the villus circumference and height tended to be greater, whereas
      crypt depth was smaller in ADLIB than in RES calves. The findings from this study
      indicate that ad libitum MR feeding for 5 wk of age followed by its gradual
      reduction promotes growth performance without any negative influence on
      gastrointestinal growth and development in dairy calves at 9 wk of age.

PMID- 29055539
TI  - Short communication: Analysis of mycotoxins in Spanish milk.
AB  - We surveyed the presence of 22 mycotoxins in 191 Spanish cow milk samples.
      Mycotoxins could be carried over from diet into animal milk and have toxic
      effects on human and animal health. The interaction of different mycotoxins may
      be additive or synergetic. Therefore, surveillance of mycotoxin co-occurrence in
      milk is recommended. Aflatoxins M1, B1, B2, G1, and G2, ochratoxins A and B,
      nivalenol, deoxynivalenol, deepoxy-deoxynivalenol, 3- and 15
      acetyldeoxynivalenol, diacetoxyscirpenol, neosolaniol, fusarenon X, T-2 and HT-2
      toxins, fumonisins B1, B2, and B3, sterigmatocystin, and zearalenone were
      analyzed. Samples were treated by liquid-liquid extraction with acidified
      acetonitrile, followed by an acetonitrile-water phase separation using sodium
      acetate. The analysis was carried out by HPLC coupled to a triple quadrupole mass
      spectrometer. None of the analyzed mycotoxins had a concentration level higher
      than their detection limit (0.05-10.1 ug/L). The aflatoxin M1 in the samples
      never exceeded the level established by the European Union.

PMID- 29055540
TI  - Short communication: Milking order consistency of dairy cows in large Australian
      herds.
AB  - We used on-farm records from dairy infrastructure to examine the consistency of
      the milking order over 150 d in 5 Australian dairy herds that were milking more
      than 500 cows as a single group. Within a single day the difference in milking
      order rank position was less than 20 percentage points for 72% of cows. The
      correlation coefficient comparing milking rank position in the morning and
      afternoon was 0.72, with the position of cows at the beginning and end of the
      milking order being more consistent than cows toward the middle of the milking
      order. Over a period of 150 d, cows with a mean position in the first and last
      20% of the milking order maintained their position more consistently than cows in
      the middle of the milking order. Milking position of cows between one month and
      the next was highly correlated (r = 0.88). In large herds, subpopulations of cows
      are regularly milked toward the beginning and the end of the milking order. It is
      common for cows to be collected from the paddock as a group, to wait as a group
      in the dairy yard to be milked, and to return individually to the paddock or feed
      pad immediately after they have been milked. Thus, cows milked later in the
      milking order are likely to be away from the paddock for several hours longer
      than cows milked earlier in the milking order. This may affect their welfare
      though differences in time available for lying down, equality of pasture eaten,
      and time spent standing in the dairy yard.

PMID- 29055541
TI  - Growth performance, rumen fermentation, nutrient utilization, and metabolic
      profile of dairy heifers limit-fed distillers dried grains with ad libitum
      forage.
AB  - The objective of this study was to determine the effects of feeding a corn- and
      soybean-product-based concentrate mix or distillers dried grains with solubles
      concentrate mix with ad libitum grass hay to dairy heifers. A 16-wk randomized
      complete block design study was conducted using 24 heifers [18 Holstein and 6
      Brown Swiss; 219 +/- 2 d of age (+/-standard deviation); 230 +/- 4 kg of body
      weight] to evaluate the effect of diet on dry matter intake (DMI), growth
      performance, rumen fermentation, metabolic profile, and nutrient digestibility.
      Treatments were (1) corn and soybean product concentrate mix, and (2) distillers
      dried-grains-with-solubles-based concentrate mix (DDG). Both concentrate mixes
      were limit-fed at 0.8% of body weight and grass hay was offered ad libitum.
      Heifers were individually fed using Calan gates and orts were recorded daily at
      feeding. Heifers were weighed every 2 wk and ration concentrate mix offered was
      adjusted accordingly. Frame measurements and body condition score were recorded
      every 2 wk. Rumen fluid was collected via esophageal tubing during wk 12 and 16
      for pH, ammonia N, and volatile fatty acid analysis. Jugular blood samples were
      collected every 4 wk for metabolite and metabolic hormone analysis. Total-tract
      digestibility of nutrients was evaluated during wk 16 by fecal grab sampling. No
      treatment by week interactions were observed for any of the growth measurements
      and growth measurements and DMI did not differ between treatments. A treatment by
      time interaction was observed for rumen butyrate percentage with heifers fed DDG
      having a greater percentage. Total volatile fatty acid concentration, acetate
      molar percentage, and acetate:propionate decreased with the DDG treatment,
      whereas propionate molar percentage increased. No treatment by week interactions
      were observed for any of the metabolites or metabolic hormones measured. A
      tendency was observed for glucose and plasma urea nitrogen concentration to
      decrease with DDG. Plasma cholesterol and insulin increased with DDG. Results
      demonstrated that limit-feeding heifers DDG at 0.8% of body weight with ad
      libitum grass hay maintained growth performance, average daily gain, DMI, and
      gain:feed, with shifts in the metabolic profile compared with the corn and
      soybean product concentrate mix.

PMID- 29055542
TI  - Extending the duration of the voluntary waiting period from 60 to 88 days in cows
      that received timed artificial insemination after the Double-Ovsynch protocol
      affected the reproductive performance, herd exit dynamics, and lactation
      performance of dairy cows.
AB  - This experiment evaluated the reproductive performance, herd exit dynamics, and
      lactation performance of dairy cows managed with a voluntary waiting period (VWP)
      of 60 or 88 d. Secondary objectives were evaluating VWP effect on cyclicity
      status, uterine health, systemic inflammation, and body condition score (BCS)
      before first service. Lactating Holstein cows from 3 commercial farms in New York
      State cows were blocked by parity group and total milk yield in their previous
      lactation and then randomly assigned to VWP of 60 (VWP60; n = 1,352) or 88
      (VWP88; n = 1,359) days in milk (DIM). All cows received the Double-Ovsynch
      protocol (GnRH-7 d-PGF2alpha-3 d-GnRH-7 d-GnRH-7 d-PGF2alpha-56 h-GnRH-16 to 20 h
      timed artificial insemination; TAI) for synchronization of ovulation and TAI. For
      second and greater artificial insemination (AI), cows received AI after detection
      of estrus or the Ovsynch protocol (GnRH-7 d-PGF2alpha-56 h-GnRH-16 to 20 h-TAI)
      initiated 32 +/- 3 d after AI for cows not re-inseminated at detected estrus.
      Cyclicity status (progesterone concentration), uterine health (vaginal discharge
      and uterine cytology), BCS, and systemic inflammation (haptoglobin concentration)
      were evaluated at baseline (33 +/- 3 DIM for both treatments), beginning of the
      Double-Ovsynch protocol, and 10 d before TAI. Effects of treatments were assessed
      with multivariable statistical methods relevant for each outcome variable.
      Extending duration of VWP from 60 to 88 DIM increased pregnancies per AI (P/AI)
      to first service (VWP60 = 41%; VWP88 = 47%). Nonetheless, the greatest benefit of
      extending VWP on first-service P/AI was for primiparous cows (VWP60 = 46%; VWP88
      = 55%), as P/AI did not differ within the multiparous cow group (VWP60 = 36%;
      VWP88 = 40%). Physiological status more conducive to pregnancy-characterized by
      improved uterine health, greater BCS, reduced systemic inflammation, and to a
      lesser extent more time to resume ovarian cyclicity-explained the increment in
      P/AI to first service. Our data also indicated that despite having greater P/AI
      to first service, cows with the longer VWP had delayed time to pregnancy during
      lactation (hazard ratio = 0.72; 95% confidence interval 0.69-0.98) and greater
      risk of leaving the herd, particularly for multiparous cows (hazard ratio = 1.34;
      95% confidence interval 1.23-1.47). This shift in pregnancy timing led to an
      overall extension of the lactation length (+13 d), which resulted in greater
      total milk yield per lactation (+491 kg) but not greater milk yield per day of
      lactation. In conclusion, data from this experiment highlight the importance of
      considering the complex interactions between reproductive performance, herd exit
      dynamics, and lactation performance as well as the effects of parity at the time
      of defining the duration of the VWP for lactating dairy cows.

PMID- 29055543
TI  - Short communication: Effect of age at group housing on behavior, cortisol,
      health, and leukocyte differential counts of neonatal bull dairy calves.
AB  - To determine the effect of age at grouping on behavior, health, and production of
      dairy bull calves, 90 Holstein-Friesian bull calves were housed in individual
      pens until moved to 1 of 3 treatments. Calves were housed in groups of 3 calves
      at 3 d old (GH3), 7 d old (GH7), or 14 d old (GH14) until 7 wk of age. Ten groups
      of 3 calves for each treatment were used, with 5 pens/treatment in each of 2
      replications (10 pens/treatment, 3 treatments, 3 calves/treatment; 90 calves
      total). Direct behavioral observations using instantaneous scan sampling every 10
      min were conducted twice per week for 7 wk. At the same times, video data were
      recorded for continuous observations at feeding time to observe the overall
      activity of group-housed calves. Hip height, heart girth, and health scores were
      recorded weekly and body weight was recorded at the start and end of the study.
      Calves in GH3 spent more time playing and but more time cross-sucking and
      displacing other calves from milk bottles. Calves engaged in social interaction
      as early as 3 d of age, and social interactions between 3 to 6 wk of age
      increased markedly. Calves housed in GH14 vocalized more than did calves in GH7
      and GH3. No difference was found between treatments in growth performance. Calf
      fecal, cough, and nasal and ocular discharge scores, differential leukocyte
      counts, and plasma cortisol concentrations were not affected by age at grouping.
      However, during the first week of grouping, when calves were moved from
      individual pens to group pens, some calves were unable to find their milk bottles
      and required guidance. In conclusion, these data show no adverse effects on
      health or performance and some benefits on social behavior for early (d 3)
      grouping of calves.

PMID- 29055544
TI  - Dry matter intake, body condition score, and grazing behavior of nonlactating,
      pregnant dairy cows fed kale or grass once versus twice daily during winter.
AB  - The objective of this study was to examine the effect of wintering pregnant,
      nonlactating dairy cows outdoors on either kale or grass, fed in 1 [11 kg dry
      matter (DM) of kale or grass + 3 kg DM of baled barley straw offered in the
      morning] or 2 allocations (5.5 kg DM of kale or grass grazed + 1.5 kg DM of
      barley straw offered morning and afternoon) per day. The body condition score
      (BCS) gain over the 47-d winter feeding period was higher for grass-fed (0.5 BCS
      units) than kale-fed cows (0.3 BCS units), but was unaffected by feeding
      frequency. Forage DM utilization was higher for kale-fed (97%) than grass-fed
      cows (76%), leading to higher estimated dry matter intake (DMI) in kale-fed (10.7
      kg of DM/cow per day) than grass-fed cows (7.7 kg of DM/cow per day). Forage DM
      utilization and estimated DMI were not affected by feeding frequency. Prehension
      bite rate was greater for grass-fed (37.3 bites/min) than kale-fed cows (7.6
      bites/min), but more mastication bites were required for kale-fed cows.
      Cumulative DMI after 2, 3, and 6 h was greater in cows allocated forage once than
      twice a day and for kale than grass after 3 and 6 h. Mean eating time was greater
      for cows offered forage once (477 min) than twice (414 min) per day. In
      conclusion, increasing feeding frequency from once to twice per day decreased the
      intake rate within the first 6 h after allocation, but did not affect total daily
      DMI, DM utilization or BCS gain. Thus, moving cows more frequently would not have
      any significant advantage. It may increase labor requirements, thereby creating a
      more challenging wintering management than feeding once per day.

PMID- 29055545
TI  - Transmission dynamics of intramammary infections caused by Corynebacterium
      species.
AB  - The development of reliable models for transmission of intramammary infections
      (IMI) is the subject of extensive research. Such models are useful to enhance the
      identification and understanding of factors that affect pathogen-specific IMI
      dynamics. Longitudinal transmission models are valuable for predicting infection
      outbreak risks, quantifying the effectiveness of response tactics, and performing
      response planning. In this work, we focused on modeling Corynebacterium spp. by
      using a compartmental model. Previous investigations have considered modeling the
      transmission dynamics of several bacterial pathogens, but not Corynebacterium
      spp. We established a Corynebacterium spp. Susceptible-Infectious-Susceptible
      (SIS) model. We simulated the model numerically by using parameters that we
      estimated by a generalized linear model approach, using month of study as the
      time variable. The data, from which the parameters of the model were estimated,
      were obtained in a field trial conducted in 2 US dairy herds. Altogether, 786
      cows were sampled at least once during the 13-mo study period. The total number
      of quarter milk cultures and cases of IMI caused by Corynebacterium spp. were
      11,744 and 556, respectively, in farm A; the corresponding figures for farm B
      were 11,804 and 179. Our modeling study included only transmission from
      persistent IMI caused by Corynebacterium spp. within the lactation pens. The rate
      of new infections was significantly related to preexisting IMI in both farms,
      underscoring the importance of preexisting Corynebacterium spp. IMI for the
      transmission of Corynebacterium spp. within lactation pens. The estimated basic
      reproduction numbers (R0) in the 2 farms were 1.18 and 0.98, respectively. The
      nonsignificant disparity in R0 was associated with significant differences in
      cure rates between farms.

PMID- 29055546
TI  - Comparison of online, hands-on, and a combined approach for teaching cautery
      disbudding technique to dairy producers.
AB  - The use of pain control for disbudding and dehorning is important from both an
      animal and industry perspective. Best practices include the use of local
      anesthetic, commonly given as a cornual nerve block (CNB), and a nonsteroidal
      anti-inflammatory drug. The proportion is decreasing, but many dairy producers do
      not use local anesthesia, perhaps in part due to lack of knowledge of the CNB
      technique. Although this skill is typically learned in person from a
      veterinarian, alternative methods may be useful. The objective of this trial was
      to determine if there were differences in the efficacy of online training (n =
      23), hands-on training (n = 20), and a combined approach (n = 23) for teaching
      producers to successfully administer a CNB and disbud a calf. The primary outcome
      was block efficacy, defined as a lack of established pain behaviors during iron
      application. Secondary outcomes were background knowledge (assessed by a written
      quiz), CNB and disbudding technique (evaluated by rubric scoring), time taken,
      and self-confidence before and after evaluation. Associations between training
      group and outcome were assessed with logistic regression, ordered logistic
      regression, and Cox-proportional hazard models, with a random effect for
      workshop. Block efficacy was not different between training groups, with 91%
      successful in both combined and online groups, and 75% in the hands-on trained
      group. Online learners had poorer technical scores than hands-on trainees. The
      combined group was not different from hands-on. Time to block completion tended
      to be longer for the online group (62 +/- 11 s), whereas time to disbudding
      completion was not different between hands-on (41 +/- 5 s) or combined trainees
      (41 +/- 5 s). The combined group had the highest pre-evaluation confidence score,
      and remained higher after evaluation than online but was not different than hands
      on. Although we saw some statistical differences between groups, absolute
      differences were small and block efficacy was similar. This suggests online
      training can be a useful tool for motivated producers who lack access to hands-on
      training.

PMID- 29055547
TI  - Chemical characterization by gas chromatography-mass spectrometry and inductively
      coupled plasma-optical emission spectroscopy of membrane permeates from an
      industrial dairy ingredient production used as process water.
AB  - Reusing reverse osmosis (RO) membrane permeate instead of potable water in the
      dairy industry is a very appealing tactic. However, to ensure safe use, the
      quality of reclaimed water must be guaranteed. To do this, qualitative and
      quantitative information about which compounds permeate the membranes must be
      established. In the present study, we provide a detailed characterization of
      ultrafiltration, RO, and RO polisher (ROP) permeate with regard to organic and
      inorganic compounds. Results indicate that smaller molecules and elements (such
      as phosphate, but mainly urea and boron) pass the membrane, and a small set of
      larger molecules (long-chain fatty acids, glycerol-phosphate, and glutamic acid)
      are found as well, though in minute concentrations (<0.2 uM). Growth experiments
      with 2 urease-positive microorganisms, isolated from RO permeate, showed that the
      nutrient content in the ROP permeate supports limited growth of 1 of the 2
      isolates, indicating that the ROP permeate may not be guaranteed to be stable
      during protracted storage.

PMID- 29055548
TI  - Short communication: Shedding of Mycoplasma bovis and antibody responses in cows
      recently diagnosed with clinical infection.
AB  - Mycoplasma bovis can have significant consequences when introduced into
      immunologically naive dairy herds. Subclinically infected carrier animals are the
      most common way that M. bovis is introduced into herds. Although M. bovis udder
      infections can be detected by milk sampling lactating animals before their
      introduction, currently, no definitive way of identifying M. bovis carrier
      animals that are nonlactating (i.e., calves, heifers, dry cows, or bulls) is
      available. Understanding the prevalence of M. bovis shedding from various body
      sites in clinically infected animals could inform strategies for the detection of
      subclinical infection in nonlactating stock. The mucosal surfaces of the nose,
      eye, and vagina of 16 cows with recent clinical mastitis caused by M. bovis were
      examined for the presence of M. bovis shedding. Blood was collected for
      serological evaluation by a commercially available ELISA. Mycoplasma bovis was
      isolated from the vagina of only 3 (18.8%) of the cows and was not detected from
      the noses or eyes of any of the cows. Fifteen of the 16 (93.8%) cows were
      seropositive to the ELISA. With such low prevalence of detection of M. bovis from
      the vagina and no detections from the noses or eyes of recently clinically
      infected animals, it is very likely that sampling these sites would be
      ineffective for detecting subclinical infection in cattle. Serology using the
      ELISA may have some use when screening animals for biosecurity risk assessment.
      However, more information regarding time to seroconversion, antibody longevity,
      and test diagnostic sensitivity and specificity are required to define the
      appropriate use of this ELISA for biosecurity purposes.

PMID- 29055549
TI  - Short communication: Effect of replacing corn with beet pulp in a high
      concentrate diet fed to weaned Holstein calves on diet digestibility and growth.
AB  - Using soluble fiber sources in starter and grower feeds for dairy calves less
      than 4 mo of age is common to reduce costs compared with including traditional
      cereal grains. Beet pulp (BP) contains relatively high concentrations of pectin
      compared with other fibrous feed ingredients and has been shown to be an
      acceptable replacement for corn in adult cow diets. However, limited information
      is available on BP digestibility and growth performance for young calves fed
      diets with BP. In this study, 48 male Holstein calves (59 +/- 2 d of age, 77 +/-
      2.2 kg of initial body weight) were fed 95% concentrate, 5% chopped grass hay
      diets in groups with 4 calves/pen for 56 d. Pens were randomly assigned to 1 of 3
      dietary treatments containing 0, 15, or 30% BP on an as-fed basis. Body weights,
      hip widths, and body condition scores were assessed at 56 (start of trial), 84,
      and 112 d of age. Dry matter intakes and refusals were recorded daily by pen.
      Digestion coefficients (dC) of the diets and microbial protein flows were
      estimated when calves were approximately 84 d of age. Fecal samples were
      collected daily from pen floors over a 7-d period, and urine samples were
      collected from 2 calves/pen over a 2-d period and analyzed for purine
      derivatives. Calf average daily gain and hip width change decreased linearly
      (from 1.09 to 1.04 kg/d and 5.4 to 4.8 cm over 56 d, respectively) with
      increasing BP. Dry matter, organic matter (from 79.7 to 75.6%), crude protein
      (75.7 to 70.1%), and starch (97.1 to 93.1%) dC decreased with increasing
      inclusion rates of BP. Conversely, neutral detergent fiber (from 47.1 to 52.7%)
      and acid detergent fiber (44.1 to 53.0%) dC increased with increasing BP.
      Estimates of urine output and microbial protein flow using purine derivatives did
      not differ among treatments. Under the conditions of this study, BP reduced
      growth largely by reducing diet digestibility in dairy calves from 56 to 112 d of
      age.

PMID- 29055550
TI  - The phylogenetic group, antimicrobial susceptibility, and virulence genes of
      Escherichia coli from clinical bovine mastitis.
AB  - Bovine mastitis is still a central problem on dairy farms despite control
      programs, and Escherichia coli is a crucial pathogen during the development of
      bovine mastitis. The virulence genes, antimicrobial susceptibility, and mortality
      of mice infected with different E. coli isolates from bovine mastitis were
      determined in this study. According to the presence of the specific genes chuA,
      yjaA, and TspE4.C2, these isolates mainly belonged to 2 different groups: group A
      (47/79) and group B1 (22/79). The ompC gene was detected in all the isolates,
      followed by fimH (89.9%), ECs3703 (88.6%), and ompF (73.4%), whereas most of the
      virulence genes were not detected in these isolates. The results of the
      antimicrobial susceptibility tests indicated that the isolates were susceptible
      to the fluoroquinolones and aminoglycosides. An inverse relationship was shown
      between the expression level of ompF and antimicrobial resistance; additionally,
      the isolates that were nonsusceptible to at least 4 classes of antimicrobial
      agents showed a lower mortality to mice in comparison with the susceptible
      isolates. This study indicated that antibiotic resistance had emerged in E. coli
      from bovine mastitis in this area, and appropriate measures should be taken to
      avoid potential threats to humans and other animals.

PMID- 29055552
TI  - Describing temporal variation in reticuloruminal pH using continuous monitoring
      data.
AB  - Reticuloruminal pH has been linked to subclinical disease in dairy cattle,
      leading to considerable interest in identifying pH observations below a given
      threshold. The relatively recent availability of continuously monitored data from
      pH boluses gives new opportunities for characterizing the normal patterns of pH
      over time and distinguishing these from abnormal patterns using more sensitive
      and specific methods than simple thresholds. We fitted a series of statistical
      models to continuously monitored data from 93 animals on 13 farms to characterize
      normal variation within and between animals. We used a subset of the data to
      relate deviations from the normal pattern to the productivity of 24 dairy cows
      from a single herd. Our findings show substantial variation in pH characteristics
      between animals, although animals within the same farm tended to show more
      consistent patterns. There was strong evidence for a predictable diurnal
      variation in all animals, and up to 70% of the observed variation in pH could be
      explained using a simple statistical model. For the 24 animals with available
      production information, there was also a strong association between productivity
      (as measured by both milk yield and dry matter intake) and deviations from the
      expected diurnal pattern of pH 2 d before the productivity observation. In
      contrast, there was no association between productivity and the occurrence of
      observations below a threshold pH. We conclude that statistical models can be
      used to account for a substantial proportion of the observed variability in pH
      and that future work with continuously monitored pH data should focus on
      deviations from a predictable pattern rather than the frequency of observations
      below an arbitrary pH threshold.

PMID- 29055551
TI  - Performance of automated activity monitoring systems used in combination with
      timed artificial insemination compared to timed artificial insemination only in
      early lactation in dairy cows.
AB  - Identifying cows in estrus remains a challenge on dairy cattle farms, and tools
      and technologies have been developed and used to complement or replace visual
      detection of estrus. Automated activity monitoring (AAM) systems and timed
      artificial insemination (TAI) are technologies available to dairy farmers, but
      many factors can influence their relative performance. The objective of the
      present study was to compare reproductive performance of cows managed with an AAM
      system combined with TAI, or with a TAI program (Double Ovsynch) for insemination
      before 88 DIM. From April 2014 to April 2015, 998 cows from 2 herds were randomly
      assigned either to be inseminated at 85 +/- 3 DIM exclusively using the Double
      Ovsynch protocol for TAI, or to be inseminated based on estrus detection by AAM
      without hormonal intervention between 50 and 75 DIM; if no alarm was detected by
      75 DIM, cows were inseminated following the single Ovsynch protocol (AAM +
      Ovsynch). The herds used different AAM systems. Parity, hyperketonemia at wk 1
      and 2 postpartum (PP), purulent vaginal discharge at wk 5 PP, body condition
      score at wk 7 PP, and anovulation to wk 9 PP were recorded. These health
      indicators did not significantly differ between treatments, but did between
      herds. The effect of treatment on pregnancy at first insemination and by 88 DIM
      were assessed using logistic regression models. Time to pregnancy was assessed
      using survival analysis. Results are reported from intention-to-treat analyses.
      Treatment did not affect pregnancy at first insemination or pregnancy by 88 DIM,
      but we found significant interactions between treatment and herd for both
      outcomes. In herd 2, marginal mean pregnancy at first AI was greater with Double
      Ovsynch (38%) than AAM + Ovsynch (31%), but no difference was observed in herd 1
      (Double Ovsynch = 31%; AAM + Ovsynch = 34%). By 88 DIM, a smaller proportion of
      cows in herd 1 were pregnant in Double Ovsynch (31%) than AAM + Ovsynch (49%),
      but there was no difference in herd 2 (Double Ovsynch = 38%; AAM + Ovsynch =
      38%). We observed a treatment by herd interaction for median (95% confidence
      interval) time to pregnancy, which were, in herd 1, 110 (106 to 129) and 98 (88
      to 113) d, and, in herd 2, 126 (113 to 139) and 116 (105 to 131) d for the Double
      Ovsynch and AAM + Ovsynch treatments, respectively. The relative performance of
      AAM-based reproductive management compared with TAI only is likely influenced by
      herd-specific variables, in particular related to insemination rate when estrus
      detection is employed.

PMID- 29055553
TI  - Effects of Leymus chinensis replacement with whole-crop wheat hay on blood
      parameters, fatty acid composition, and microbiomes of Holstein bulls.
AB  - This study investigated the replacement of Leymus chinensis (LC) with whole-crop
      wheat hay (WCWH) in the diets of Holstein bulls in the fattening stage and
      examined the potential effects on blood parameters, fatty acids in rumen fluid
      and serum, and the rumen microbiomes. In this study, 12 Holstein bulls in the
      fattening period (body weight = 485.0 +/- 40.8 kg) were assigned to 1 of 4
      dietary treatments using a 4 * 4 Latin square design. Each experimental period
      consisted of a 17-d adaptation period and a 5-d collection period. The dietary
      treatments consisted of 4 proportions of WCWH (0, 33, 67, and 100%) as a
      substitute for LC (designated as WCWH0, WCWH33, WCWH67, and WCWH100,
      respectively). On d 18 and 22 of each experiment period, blood and rumen content
      samples were collected for analysis, respectively. Real-time quantitative PCR was
      used to analyze the rumen microbiomes. The results from this study revealed no
      differences in the saturated, monounsaturated, and polyunsaturated long-chain
      fatty acid proportions of rumen liquid among the treatments. It was observed in
      the present trial that rumen microbiotal flora were not significantly different
      in the bulls fed LC compared with the bulls fed WCWH. Additionally, blood sample
      analysis demonstrated that the concentration of urea nitrogen in the WCWH100
      group was higher than that observed in the other groups. Meanwhile, no
      differences were detected for other serum parameters. There were no differences
      in the proportions of serum saturated, monounsaturated, and polyunsaturated long
      chain fatty acids among the treatments. In conclusion, our data revealed that LC
      can be replaced with WCWH in the diet of Holstein bulls in the fattening stage
      with no negative effects on the blood indicators, fatty acids, and microbiomes.

PMID- 29055554
TI  - Preventing central venous line related bloodstream infections in adult ICUs:
      Start from the basics and bundle.

PMID- 29055555
TI  - [Most advisable strategy in search of asymptomatic target organ damage in
      hypertensive patients].

PMID- 29055556
TI  - Transcatheter Aortic Valve, Impella and Complex Coronary Intervention.

PMID- 29055557
TI  - Transcatheter Tricuspid Repair With MitraClip in a Patient With a Failing De Vega
      Annuloplasty.

PMID- 29055558
TI  - Pelvic fractures after definitive and postoperative radiotherapy for cervical
      cancer: A retrospective analysis of risk factors.
AB  - OBJECTIVES: This study clarified the incidence of and identified the risk factors
      for post-radiation pelvic insufficiency fractures (PIFs) in women who received
      postoperative definitive or adjuvant radiotherapy (RT) for cervical cancer.
      PATIENTS AND METHODS: The medical records and data of imaging studies, including
      computed tomography scan and magnetic resonance imaging, of women with cervical
      cancer who received external-beam RT for the entire pelvic area between January
      2003 and December 2012 at our institution were reviewed. RESULTS: A total of 533
      patients with histologically diagnosed cervical cancer who received RT (298:
      definitive RT, 235: adjuvant RT) were included in this study. Eighty-four
      patients (15.8%) developed PIF in the irradiated field. Median age at onset of
      PIF was 72.5years (range: 54-95years), and 82 of them (98%) were postmenopausal
      women. Sixty-nine patients (80%) developed PIF within 3years from the completion
      of RT. The median time for the development of PIF was 14months (range: 1
      81months). The most commonly involved fracture site was the sacral bone.
      Postmenopausal state, coexistence of rheumatoid arthritis, and high-dose-rate
      intracavitary brachytherapy (HDR-ICBT) use were significant predisposing factors
      for the development of PIF, according to multivariate analysis. CONCLUSIONS: The
      incidence rate of PIF among patients who received RT for locally advanced
      cervical cancer was 15.8%. The principal predisposing factors for post-radiation
      PIF were postmenopausal state, rheumatoid arthritis, and HDR-ICBT use. Active
      interventions, including bone density screening followed by medication, should be
      considered during the early stage of RT for women with high-risk factors of PIF.

PMID- 29055559
TI  - Physiological and molecular responses of Prorocentrum donghaiense to dissolved
      inorganic phosphorus limitation.
AB  - Prorocentrum donghaiense is an important dinoflagellate as it frequently forms
      harmful algal blooms that cause serious damage to marine ecosystems and fisheries
      in the coast of East China Sea. Previous studies showed that phosphorus
      acquisition (especially inorganic phosphorus) was the limiting factor for P.
      donghaiense growth. However, the responsive mechanism of this microalga under
      dissolved inorganic phosphorus (DIP) limitation is poorly understood. In this
      work, the physiological parameters and differentially expressed genes in P.
      donghaiense response to DIP limitation were comparatively analyzed. DIP-depleted
      P. donghaiense displayed decreased growth rate, enlarged cell size, decreased
      cellular phosphorus content, and high AP activities. A forward suppression
      subtractive hybridization (SSH) library representing differentially upregulated
      genes in P. donghaiense under DIP-depleted conditions was constructed, and 134
      ESTs were finally identified, with a significant identity (E values<1*10-4) to
      the deposited genes (proteins) in the corresponding databases. Five
      representative genes, namely, NAD-dependent deacetylase, phosphoglycolate
      phosphatase, heat shock protein (HSP) 90, rhodopsin, and HSP40 were investigated
      through real-time quantitative PCR to verify the effectiveness of the established
      SSH library. Results showed that all the selected genes were differentially
      expressed and thus indicated that the established SSH library generally
      represented differentially expressed genes. These genes were classified into 11
      categories according to their gene ontology annotations of biological processes.
      The members involved in functional responses such as cell defense/homeostasis,
      phosphorus metabolism, and cellular cycles were specially discussed. This study
      is the first to perform a global analysis of differentially expressed functional
      genes in P. donghaiense under DIP-depleted condition. It provided new insights
      into the molecular adaptive mechanisms of dinoflagellate in response to
      phosphorous limitation and elucidating the formation mechanism of algal blooms.

PMID- 29055560
TI  - Plastic pollution in the Labrador Sea: An assessment using the seabird northern
      fulmar Fulmarus glacialis as a biological monitoring species.
AB  - Plastic is now one among one of the most pervasive pollutants on the planet, and
      ocean circulation models predict that the Arctic will become another accumulation
      zone. As solutions to address marine plastic emerge, is essential that baselines
      are available to monitor progress towards targets. The northern fulmar (Fulmarus
      glacialis), a widely-distributed seabird species, has been used as a biological
      monitor for plastic pollution in the North Sea, and could be a useful monitoring
      species elsewhere. We quantified plastic ingested by northern fulmars from the
      southeastern Canadian waters of the Labrador Sea with the objective of
      establishing a standardized baseline for future comparisons. Over two years we
      sampled 70 fulmars and found that 79% had ingested plastic, with an average of
      11.6 pieces or 0.151g per bird. Overall, 34% of all fulmars exceeded the
      Ecological Quality Objective for marine litter, having ingested >0.1g of plastic.

PMID- 29055561
TI  - Improving the monitoring of a dumping site in a dynamic environment. Example of
      the Octeville site (Bay of Seine, English Channel).
AB  - Dredged sediments have different physical and chemical characteristics compared
      with the sediments in place, which generates multiple effects on the environment.
      In this study, we show that the sampling strategy used to monitor the effects of
      dredge spoil deposition on the surrounding environment can lead to different
      interpretations. It appears that sediment sample replicates may or may not be
      necessary, depending on the studied area, the prevailing environmental forcings
      before sediment sampling and the combination of these two factors. The proposed
      modus operandi allows us to optimize both the confidence on the obtained results
      and the cost of the sediment studies (sampling and laboratory analyses). The
      results are based on the sediment fine fraction, which is considered as a key
      environmental component due, for example, to its strong association with the
      structure of benthic faunal communities as well as its role in the build-up of
      pollutants.

PMID- 29055562
TI  - Chemical characteristics of dissolved mercury in the pore water of Minamata Bay
      sediments.
AB  - Methylmercury concentrations in fish from the historically polluted Minamata Bay
      remain higher than in fish from other coastal seas around Japan. To obtain a
      better understanding of this phenomenon, the chemical characteristics of pore
      water from Minamata Bay sediments were investigated. Samples were taken from two
      stations over a 1-year period. Total average values in the pore water at the two
      stations for dissolved total mercury and methylmercury concentrations were 6.64+/
      4.93 and 2.69+/-2.07ng/l, respectively. The pore water was centrifuged at 1000rpm
      to 3000rpm. The highest ratio of dissolved methylmercury to dissolved total
      mercury exceeded 60% for pore water centrifuged at 3000rpm. Furthermore, because
      total average values of Log Kd of total mercury and methylmercury in sediment
      (St1 and St2) were 5.42 and 2.32 (Lkg-1), methylmercury in Minamata Bay sediment
      is more eluted than other mercury species.

PMID- 29055563
TI  - Biodegradation of anthracene and several PAHs by the marine-derived fungus
      Cladosporium sp. CBMAI 1237.
AB  - The biodegradation of polycyclic aromatic hydrocarbons (PAHs) by marine-derived
      fungi was reported in this work. Marine-derived fungi (Trichoderma harzianum
      CBMAI 1677, Cladosporium sp. CBMAI 1237, Aspergillus sydowii CBMAI 935,
      Penicillium citrinum CBMAI 1186 and Mucor racemosus CBMAI 847) biodegraded
      anthracene (14days, 130rpm, 50mgmL-1 initial concentration in malt 2% medium).
      Cladosporium sp. CBMAI 1237 was the most efficient strain and biodegraded more
      anthracene in the presence (42% biodegradation) than in the absence (26%) of
      artificial seawater, suggesting that the biodegradation of PAHs may be faster in
      seawater than in non-saline environment. After 21days, Cladosporium sp. CBMAI
      1237 biodegraded anthracene (71% biodegradation), anthrone (100%), anthraquinone
      (32%), acenaphthene (78%), fluorene (70%), phenanthrene (47%), fluoranthene
      (52%), pyrene (62%) and nitropyrene (64%). Previous undocumented metabolites were
      identified and, anthraquinone was a common product of different PAHs
      biodegradation. The marine-derived fungus Cladosporium sp. CBMAI 1237 showed
      potential for bioremediation of PAHs.

PMID- 29055564
TI  - The effects of systemic treatment with aminobisphosphonates and statins on
      circulating Vgamma9Vdelta2-T cells in patients with advanced cancer.
AB  - Aminobisphosphonates (NBP) are used for treatment of metastatic bone disease.
      Frequently, patients undergoing NBP-treatment experience side-effects, known as
      acute phase response (APR), resulting from cytokine production by Vgamma9Vdelta2
      T cells. As opposed to NBP, statins reduce intracellular phosphoantigen levels
      and prevent NBP-induced Vgamma9Vdelta2-T cell activation in vitro. We conducted a
      pilot study in patients with (bone-)metastasized malignancies receiving NBP
      treatment and evaluated the phenotype and function of circulating Vgamma9Vdelta2
      T cells in vivo and the effects of statins on Vgamma9Vdelta2-T cell responses and
      the associated APR. We observed reduced expression of perforin, granzyme B and
      HLA-DR on Vgamma9Vdelta2-T cells in patients treated with NBP and statins.
      However, statins could not prevent NBP-induced changes in circulating
      Vgamma9Vdelta2-T cell numbers or production of IFNgamma and TNFalpha. Consistent
      with this, simvastatin could not prevent the occurrence of APR upon NBP-infusion.
      These observations call for the exploration of alternative strategies to prevent
      collateral APR upon NBP treatment.

PMID- 29055565
TI  - Characterization of B7H6, an endogenous ligand for the NK cell activating
      receptor NKp30, reveals the identity of two different soluble isoforms during
      normal human pregnancy.
AB  - B7H6, an endogenous ligand expressed on tumor cell surfaces, triggers NKp30
      mediated activation of human NK cells. In contrast, the release of soluble B7H6
      has been proposed as a novel mechanism by which tumors might evade NK cell
      mediated recognition. Since NK cells are critical for the maintenance of early
      pregnancy, it is not illogical that soluble B7H6 might also be an important
      factor in directing NK cell activity during normal pregnancy. Thus, this study
      was focused on the characterization of soluble B7H6 during the development of
      normal pregnancy. Serum samples were obtained from healthy pregnant women who
      were experiencing their second pregnancies (n=36). Additionally, 17 of these
      pregnant participants were longitudinally studied for the presence of B7H6 during
      their second and third trimesters. Age-matched healthy non-pregnant women served
      as controls (n=30). The presence of soluble B7H6 was revealed by Western
      blotting. A further characterization was performed using an immunoproteomic
      approach based on 2DE-Western blotting combined with MALDI-MS. The results show
      that sera from all pregnant women were characterized by the presence of two novel
      isoforms of B7H6, both with lower MW than the reported of 51kDa. These isoforms
      were either a heavy (~37kDa) or a light isoform (~30kDa) and were mutually
      exclusive. N-glycosylation did not completely explain the different molecular
      weights exhibited by the two isoforms, as was demonstrated by enzymatic
      deglycosylation with PNGase F. The confirmation of the identity and molecular
      mass of each isoform indicates that B7H6, while maintaining the C- and N-termini,
      is most likely released during pregnancy by a mechanism distinct from proteolytic
      cleavage. We found that both isoforms, but mainly the heavier B7H6, were released
      via exosomes; and that the lighter isoform was also released in an exosome-free
      manner that was not observed in the heavy isoform samples. In conclusion, we find
      that soluble B7H6 is constitutively expressed during pregnancy and that,
      moreover, the soluble B7H6 is present in two new isoforms, which are released by
      exosomal and exosome-free mechanisms.

PMID- 29055566
TI  - Serum interleukin-6 levels are increased in HIV-infected patients that develop
      autoimmune disease during long-term follow-up.
AB  - BACKGROUND: Elevated IL-6 levels have been associated with both autoimmune
      diseases and treated HIV-seropositive (HIV+) subjects. However, few data on
      classic and trans-signaling IL-6 in autoimmune thyroid diseases and HIV+ subjects
      developing autoimmune disorders are currently available. MATERIALS AND METHODS: A
      total of 102 patients were included in the study. They were subdivided into two
      groups. Group A consisted in 51 HIV+ patients, who were followed-up for a period
      of five years in search of possible occurrence of autoimmune diseases. Ten of
      them, treated with antiretroviral therapy (ART), developed an autoimmune
      disorder, namely Hashimoto's thyroiditis, and psoriasis. Group B consisted in 51
      patients affected by Hashimoto's thyroiditis (HT). Serum levels of the free form
      of IL-6 were analyzed by ELISA in all patients and for HIV+ patients at the
      beginning of the follow-up, before initiation of ART. RESULTS: Mean serum levels
      of IL-6 were similar in Group A and in Group B. In Group B, IL-6 levels showed a
      5.8% increase compared with assay minimum detectable dose corresponding to 1% of
      full serum IL-6 level. However, serum levels of free IL-6 were increased in those
      HIV+ patients who developed autoimmune disorders (5.8+/-2.8pg/ml) and in these
      patients, the highest levels of free IL-6 correlated with age and CD4 cellular
      counts. CONCLUSIONS: The present study indicates a correlation between serum free
      IL-6 levels and the occurrence of autoimmune disease in HIV+ population, treated
      with ART during a long-term follow-up. The increased levels of serum free IL-6
      were observed before ART treatment was initiated, indicating that IL-6
      measurement in such patients may represent an early predictor of development of
      autoimmune disease.

PMID- 29055568
TI  - Integrated analysis supports ATXN1 as a schizophrenia risk gene.
AB  - Protein-protein interaction (PPI) is informative in identifying hidden disease
      risk genes that tend to interact with known risk genes usually working together
      in the same disease module. With the use of an integrated approach combining PPI
      information with pathway and expression analysis as well as genome-wide
      association study (GWAS), we intended to find new risk genes for schizophrenia
      (SCZ). We showed that ATXN1 was the only direct PPI partner of the know SCZ risk
      gene ZNF804A, and it also had direct PPIs with other 18 known SCZ risk genes.
      ATXN1 serves as one of the hub genes in the PPI network containing many known SCZ
      risk genes, and this network is significantly enriched for the MAPK signaling
      pathway. Further gene expression analysis indicated that ATXN1 is highly
      expressed in prefrontal cortex, and SCZ patients had significantly decreased
      expression compared with healthy controls. Finally, the published GWAS data
      supports an association of ATXN1 with SCZ as well as other psychiatric disorders
      though not reaching genome-wide significance. These convergent evidences support
      ATXN1 as a promising risk gene for SCZ, and the integrated approach serves as a
      useful tool for dissecting the genetic basis of psychiatric disorders.

PMID- 29055567
TI  - The Ultra-High-Risk for psychosis groups: Evidence to maintain the status quo.
AB  - Individuals are considered Ultra-High-Risk (UHR) for psychosis if they meet a set
      of standardised criteria including presumed genetic vulnerability (Trait), or a
      recent history of Attenuated Psychotic Symptoms (APS) or Brief Limited
      Intermittent Psychotic Symptoms (BLIPS). Recent calls to revise these criteria
      have arisen from evidence that Trait, APS and BLIPS groups may transition to
      psychosis at different rates. Concurrently, it has become clear that the UHR
      status confers clinical risk beyond transition to psychosis. Specifically, most
      UHR individuals will not develop psychosis, but will experience high rates of non
      psychotic disorders, persistent APS and poor long-term functional outcomes.
      Rather than focus on transition, the present study investigated whether UHR
      groups differ in their broader clinical risk profile by examining baseline
      clinical characteristics and long-term outcomes other than transition to
      psychosis. Four UHR groups were defined: Trait-only, APS-only, Trait+APS, and any
      BLIPS. Participants (N=702) were recruited upon entry to early intervention
      services and followed-up over a period of up to 13years (mean=4.53, SD=3.84). The
      groups evidenced similar symptom severity (SANS for negative symptoms, BPRS for
      positive and depression/anxiety symptoms) and psychosocial functioning (SOFAS,
      GAF, QLS) at baseline and follow-up as well as similar prevalence of non
      psychotic disorders at follow-up. Our findings demonstrate that UHR groups
      evidence a similar clinical risk profile when we expand this beyond transition to
      psychosis, and consequently support maintaining the existing UHR criteria.

PMID- 29055569
TI  - The association between changes in depression/anxiety and trajectories of
      psychotic-like experiences over a year in adolescence.
AB  - BACKGROUND: Recent cross-sectional studies suggest that psychotic-like
      experiences (PLEs) are associated with depression and anxiety in adolescents.
      While longitudinal studies have observed that adolescents suffer more severe
      symptoms of depression/anxiety when PLEs persist, it remains unclear whether
      depression/anxiety worsens or improves with PLE emergence or remission,
      respectively. In this prospective school-based study, we investigated the
      association between longitudinal changes in depression/anxiety and one-year PLE
      trajectories in adolescence. METHODS: Nine hundred and twelve adolescents
      participated in the baseline assessment of PLEs and depression/anxiety; 887
      (97.3%) adolescents completed the follow-up assessment one year later. Multilevel
      analysis was conducted to evaluate the change in depression/anxiety, evaluated
      using the General Health Questionnaire-12 (GHQ-12), during the year according to
      PLE trajectory, adjusting for baseline depression/anxiety, gender, age, substance
      use and victimization. RESULTS: Sixteen percent of adolescents reported PLEs at
      baseline, with 56% of them remitting at follow-up. At follow-up, PLEs were
      experienced by 6.6% of adolescents not experiencing PLEs at baseline (incident
      PLE group). After adjusting for covariates, GHQ-12 score worsened significantly
      during the year in students with incident trajectories (regression coefficient
      for time, alpha1=1.91, 95% CI: 1.04-2.77), but in those showing remission, GHQ-12
      score did not significantly improve (alpha1=-0.20, 95% CI: -0.97-0.56).
      CONCLUSIONS: Greater awareness about PLEs and their trajectories in school health
      care settings may be a key towards the prevention and treatment of adolescent
      depression and anxiety.

PMID- 29055570
TI  - Surgical and social implications of extraction of mandibular third molars as a
      separate procedure before bilateral sagittal split osteotomy.
AB  - In some units, lower wisdom teeth are extracted in a separate procedure before
      bilateral sagittal split osteotomy (BSSO), whereas in others they are removed at
      the time of the osteotomy. We identified 57 patients who had BSSO at Salisbury
      Hospital between October 2013 and September 2015, 40 of whom had their wisdom
      teeth extracted at the same time. The remaining 17 did not have wisdom teeth.
      Patients who have these teeth extracted as a separate procedure require at least
      one day off work, which can result in a loss of earnings. Our findings showed
      that the removal of third molars at the time of orthognathic surgery has
      considerable social and financial benefits, and does not increase the risk of
      morbidity.

PMID- 29055571
TI  - Evaluation of facial blood flow using three-dimensional scanning.
AB  - The Vectra X3 3-dimensional face scanner allows us to visualise the erythema of
      superficial layers of skin in addition to its regular scanning functions. The aim
      of our study was to find out whether changes we provoked in the circulation of
      the skin would be registered and displayed by the face scanner. We measured the
      circulation in the skin of the cheeks of 20 volunteers with a face scanner, a
      laser Doppler device, and a skin pigmentation analyser before and after the
      application of a nitric oxide cream. The results were compared in terms of grey
      tones, local concentrations of haemoglobin, and erythema. All methods showed
      significant changes (p<0.001) before and after application of the cream. The
      study proved that the Vectra X3 recognises changes in skin circulation and
      displays them in a simple and evident way.

PMID- 29055572
TI  - Prescription of antibiotics: does it alter the outcome for patients who have
      fractures of the angle of the mandible?
AB  - We retrospectively studied 708 consecutive patients at the Queen Elizabeth
      Hospital, Birmingham, to find out whether one of the four antibiotic protocols in
      use conferred any advantage (or disadvantage) on a patient who had a fractured
      angle of the mandible, and there was none. However, the time from initial injury
      until the time of the first dose of antibiotic was important. Clinically, if
      patients waited more than 72hours after the injury before the first dose of
      antibiotic was given, they had a three times higher rate of postoperative
      infection than patients who were given their first dose between 24 and 72hours
      after the injury. Morbidity was more than five times higher during the
      postoperative period if the patient had waited for three days before their first
      dose, compared with those given the first dose within eight hours of injury. The
      overall rate of malunion or non-union of the fracture was between five and 10
      times higher if the patient had waited more than 72hours after injury compared
      with all the other groups. There was a considerable difference in cost between
      the intravenous and oral versions of the antibiotics used (Augmentin(r) and
      metronidazole) so, if it could be shown that the oral doses are as efficacious as
      intravenous doses, a great deal of money could be saved.

PMID- 29055573
TI  - Bleomycin electrosclerotherapy: new treatment to manage vascular malformations.
AB  - Venous malformations are congenital anomalies of the vascular system. The
      injection of bleomycin (a cytotoxic, antitumour drug) into the lesion is a safe
      and effective treatment for low-flow (venous and lymphatic) malformations, but
      its use systemically has been associated with pulmonary fibrosis. Intralesional
      injection of bleomycin is considered to have a lower risk, but caution should be
      used when planning treatment, with particular regard to respiratory function.
      Electroporation is the temporary application of an electrical field across a
      tissue to increase (briefly) the permeability of the cell membrane in that
      tissue. We successfully treated a venous malformation in a patient with severe
      respiratory compromise with a low dose of bleomycin into the lesion, which we
      augmented using electroporation. To the best of our knowledge, this is the first
      reported use of bleomycin electrosclerotherapy in the management of a venous
      malformation.

PMID- 29055574
TI  - Spiral shape microfluidic channel for selective isolating of heterogenic
      circulating tumor cells.
AB  - Detecting heterogenic tumor cells that are traveling in our body through blood
      stream for the tumor metastasis is one way for cancer prognosis. Due to the
      heterogeneity of circulating tumor cells (CTCs), further identification of tumor
      cell types should be accompanied with CTCs isolation from blood cells in
      peripheral blood sample. Both negative enrichment and recollection of isolated
      CTCs are required in the downstream analysis, which are time-consuming, labor
      intensive, and massive equipment required. To solve these limitations, we have
      developed a simple and disposable spiral shape microfluidic channel that can
      separate all CTCs from blood cells, and at the same time, can identify the types
      of CTCs based on epithelial cell adhesion molecule (EpCAM) expression level. Two
      different types of tumor cells, MCF-7 and MDA-MB-231, both from the same origin
      of breast carcinoma cells, were used to demonstrate the functionality of the
      developed system. The spiral channel system could capture the EpCAM positive and
      negative CTCs with 96.3% and 81.2% purity, respectively, while both EpCAM
      positive and negative CTCs were differently positioned along the microfluidic
      channel. The average selectivity of EpCAM positive and negative CTCs is 6.1:4.8.
      In addition, the throughput of the system was optimized at a sample flow rate of
      150ul/min. The developed system successfully demonstrated its potential to
      identify biomarkers, including EpCAM, for detecting the heterogenic CTCs.

PMID- 29055575
TI  - Review of levoglucosan in glacier snow and ice studies: Recent progress and
      future perspectives.
AB  - Levoglucosan (LEV) in glacier snow and ice layers provides a fingerprint of fire
      activity, ranging from modern air pollution to ancient fire emissions. In this
      study, we review recent progress in our understanding and application of LEV in
      glaciers, including analytical methods, transport and post-depositional
      processes, and historical records. We firstly summarize progress in analytical
      methods for determination of LEV in glacier snow and ice. Then, we discuss the
      processes influencing the records of LEV in snow and ice layers. Finally, we make
      some recommendations for future work, such as assessing the stability of LEV and
      obtaining continuous records, to increase reliability of the reconstructed
      ancient fire activity. This review provides an update for researchers working
      with LEV and will facilitate the further use of LEV as a biomarker in paleo-fire
      studies based on ice core records.

PMID- 29055576
TI  - MAIAC-based long-term spatiotemporal trends of PM2.5 in Beijing, China.
AB  - Satellite-driven statistical models have been proven to be able to provide
      spatially resolved PM2.5 estimates worldwide. The North China Plain has been
      suffering from severe PM2.5 pollution in recent years. An accurate assessment of
      the spatiotemporal characteristics of PM2.5 levels in this region is crucial to
      design effective air pollution control policy. Our objective is to estimate daily
      PM2.5 concentrations at 1km spatial resolution from 2004 to 2014 in Beijing and
      its surrounding areas using the Multi-angle implementation of atmospheric
      correction (MAIAC) aerosol optical depth (AOD). A high-performance three-stage
      model was developed with AOD, meteorological, demographic and land use variables
      as predictors, which includes a custom-designed PM2.5 gap-filling method. The 11
      year average annual coverage increased from 177days to 279days and annual PM2.5
      prediction error decreased from 14.1MUg/m3 to 8.3MUg/m3 after gap-filling
      techniques were applied. Results show that the 11-year overall mean of predicted
      PM2.5 was 67.1MUg/m3 in our study domain. The cross-validation R2 value of our
      model is 0.82 in 2013 and 0.79 in 2014. In addition, the models predicted
      historical PM2.5 concentrations with relatively high accuracy at the seasonal and
      annual levels (R2 ranged from 0.78 to 0.86). Our long-term PM2.5 prediction
      filled the gaps left by ground monitors, which would be beneficial to PM2.5
      related epidemiological studies in Beijing.

PMID- 29055577
TI  - Evidence of high di(2-ethylhexyl) phthalate (DEHP) exposure due to tainted food
      intake in Taiwanese pregnant women and the health effects on birth outcomes.
AB  - The contamination of a clouding agent with di(2-ethylhexyl) phthalate (DEHP), a
      substitute emulsifier-containing compound used in a variety of foods was
      announced on May 23, 2011. The aims of this study were as follows (1) compare the
      urine phthalates (PAE) metabolites concentration and estimate the daily intake
      (DI) of PAEs in pregnant women before and after the tainted food scandal and (2)
      examine the effect of relatively high PAEs exposure on birth outcome. One-hundred
      twelve pregnant women in Northern Taiwan participated in this study from March to
      December 2010, i.e., before the tainted food scandal. After the tainted food
      scandal, we collected 69, 73, and 180 urine specimens (January 2013 to August
      2014) from women whom were in their first, second, and third trimesters of
      pregnancy, respectively. We measure urinary DEHP metabolite concentrations to
      estimate the DI of DEHP and the hazard quotient (HQ) of subjects. This was the
      first study to assess the effects of DEHP-tainted food scandal exposure in
      pregnant women across the three trimesters of pregnancy. After the tainted food
      report, the concentrations of urine PAE metabolite were significantly decreased,
      especially those of DEHP metabolites. Based on different reference limit values,
      the percentages of pregnant women whose HQDEHP value exceeded the limit ranged
      from 0.53% to 8.93%. Despite this low frequency, the higher SigmaPAE exposure
      during the second trimester may significantly increase the risk of relatively low
      birth height compared to the lower exposure group (beta=-0.63 (-1.20 to -0.06)).
      Our results support the hypothesis that exposure to relatively high
      concentrations of DEHP in pregnant Taiwanese women may have an adverse effect on
      birth outcomes. The percentage of subjects whose exposure level exceeded the
      exposure limit was low; however, high PAEs exposure appears to be significantly
      associated with birth outcomes. Therefore, we suggest that reference dose for
      PAEs should be revised.

PMID- 29055579
TI  - Quantifying longitudinal land use change from land degradation to rehabilitation
      in the headwaters of Tekeze-Atbara Basin, Ethiopia.
AB  - The spatiotemporal variability of the Land Use/Cover (LULC) is a strong influence
      on the land management and hydrological processes of a river basin. In particular
      in semi-arid regions like the Tekeze-Atbara (T-A) basin, accurate information
      about LULC change is a prerequisite for improved land and water management. The
      human-induced landscape transformations in the T-A basin, one of the main
      tributaries of the Nile River, were investigated for the last four decades (1972
      2014). Separate LULC maps for the years 1972, 1989, 2001, and 2014 were developed
      based on satellite images, Geographic Information System (GIS) and ground
      information. Change detection analysis based on the transitional probability
      matrix was applied to identify systematic transitions among the LULC categories.
      The results show that >72% of the landscape has changed its category during the
      past 43years. LULC in the basin experienced significant shifts from one category
      to other categories by 61%, 47%, and 45%, in 1972-1989, 1989-2001, and 2001-2014,
      respectively. Although both net and swap (simultaneous gain and loss of a given
      LULC during a certain period) change occurred, the latter is more dominant.
      Natural vegetation cover, including forests, reduced drastically with the rapid
      expansion of crops, grazing areas and bare lands during the first two decades.
      However, vegetation started to recover since the 1990s, when some of the
      agricultural and bare lands have turned into vegetated areas. Forest land showed
      a continuous decreasing pattern, however, it has increased by 28% in the last
      period (2001-2014). In contrast, plantation trees have increased by 254% in the
      last three decades. The increase of vegetation cover is a result of intensive
      watershed management programs during the last two decades. The driving forces of
      changes were also discussed and rapid population growth and changing government
      policies were found to be the most important.

PMID- 29055578
TI  - Trace elements in Mediterranean seagrasses and macroalgae. A review.
AB  - This review investigates the current state of knowledge on the levels of the main
      essential and non-essential trace elements in Mediterranean vascular plants and
      macroalgae. The research focuses also on the so far known effects of high element
      concentrations on these marine organisms. The possible use of plants and algae as
      bioindicators of marine pollution is discussed as well. The presence of trace
      elements is overall well known in all five Mediterranean vascular plants, whereas
      current studies investigated element concentrations in only c. 5.0% of all native
      Mediterranean macroalgae. Although seagrasses and macroalgae can generally
      accumulate and tolerate high concentrations of trace elements, phytotoxic levels
      are still not clearly identified for both groups of organisms. Moreover, although
      the high accumulation of trace elements in seagrasses and macroalgae is
      considered as a significant risk for the associated food webs, the real magnitude
      of this risk has not been adequately investigated yet. The current research
      provides enough scientific evidence that seagrasses and macroalgae may act as
      effective bioindicators, especially the former for trace elements in sediments,
      and the latter in seawater. The combined use of seagrasses and macroalgae as
      bioindicators still lacks validated protocols, whose application should be
      strongly encouraged to biomonitor exhaustively the presence of trace elements in
      the abiotic and biotic components of coastal ecosystems.

PMID- 29055580
TI  - Assessment of ecosystem health disturbance in mangrove-lined Caribbean coastal
      systems using the oyster Crassostrea rhizophorae as sentinel species.
AB  - This investigation was aimed at contributing to develop a suitable multi
      biomarker approach for pollution monitoring in mangrove-lined Caribbean coastal
      systems using as sentinel species, the mangrove cupped oyster, Crassostrea
      rhizophorae. A pilot field study was carried out in 8 localities (3 in Nicaragua;
      5 in Colombia), characterized by different environmental conditions and subjected
      to different levels and types of pollution. Samples were collected in the rainy
      and dry seasons of 2012-2013. The biological effects at different levels of
      biological complexity (Stress-on-Stress response, reproduction, condition index,
      tissue-level biomarkers and histopathology) were determined as indicators of
      health disturbance, integrated as IBR/n index, and compared with tissue burdens
      of contaminants in order to achieve an integrative biomonitoring approach. Though
      modulated by natural variables and confounding factors, different indicators of
      oyster health, alone and in combination, were related to the presence of
      different profiles and levels of contaminants present at low-to-moderate levels.
      Different mixtures of persistent (As, Cd, PAHs) and emerging chemical pollutants
      (musk fragrances), in combination with different levels of organic and
      particulate matter resulting from seasonal oceanographic variability and sewage
      discharges, and environmental factors (salinity, temperature) elicited a
      different degree of disturbance in ecosystem health condition, as reflected in
      sentinel C. rhizophorae. As a result, IBR/n was correlated with pollution
      indices, even though the levels of biological indicators of health disturbance
      and pollutants were low-to-moderate, and seasonality and the incidence of
      confounding factors were remarkable. Our study supports the use of simple
      methodological approaches to diagnose anomalies in the health status of oysters
      from different localities and to identify potential causing agents and reflect
      disturbances in ecosystem health. Consequently, the easy methodological approach
      used herein is useful for the assessment of health disturbance in a variety of
      mangrove-lined Caribbean coastal systems using mangrove cupped oysters as
      sentinel species.

PMID- 29055582
TI  - Assessment of ecosystem productivity damage due to land use.
AB  - Land use can affect ecosystems on land and their services. Because land use has
      mainly local effects, damage to ecosystem productivity due to land use should be
      modelled spatially dependent. Unfortunately, even though land use of impacts are
      particular importance for countries whose economies are highly agriculture-based,
      ecosystem productivity damage due to land use has not yet been assessed in
      Thailand so far. This study presents the method for assessing the damage to
      ecosystem productivity due to land use (land occupation and land transformation)
      in Thailand. Ecosystem productivity damage is expressed through net primary
      production (NPP). To convert the damage into monetary units, this study performs
      an economic valuation of NPP using the production function approach. The results
      show that the value of marginal product of NPP is around 10-15 Thai baht (THB) (1
      USD~36 THB), per tonne dry weight biomass. The results are applied to the case of
      biodiesel production. The method presented in this paper could be a guideline for
      future land use impact assessment research. In addition, converting the NPP
      damage results into monetary units facilitates integration of impact assessment
      and economic analysis results for supporting decision support tools such as cost
      benefit analysis.

PMID- 29055581
TI  - The toxicity of ionic liquid 1-decylpyridinium bromide to the algae Scenedesmus
      obliquus: Growth inhibition, phototoxicity, and oxidative stress.
AB  - Although ionic liquids (ILs) are unlikely to act as air contaminants, their high
      solubility and slow degradation make them a potential threat to the aquatic
      environment. The IL 1-decylpyridinium bromide ([DPy]Br) is a common type of
      pyridine IL, which has varied applications such as in extraction, separation, and
      catalytic synthesis. Herein, the toxicity of [DPy]Br to S. obliquus is
      determined. Growth was inhibited by high-concentration [DPy]Br, whereas it had a
      hormetic effect at low concentrations. The IC50-96h was approximately 0.06mg/L.
      The cell membrane permeability of S. obliquus increased with [DPy]Br
      concentration, indicating that [DPy]Br can cause damage to the algae cell
      structure. Chlorophyll content decreased at high [DPy]Br concentration;
      chlorophyll fluorescence parameters, such as the maximum effective quantum yield
      of PSII (Fv/Fm), potential activity of PSII (Fv/F0), yield of the photochemical
      quantum [Y(II)], and the non-photochemical quenching coefficient (NPQ) were
      affected, suggesting that [DPy]Br can damage PSII. The ROS fluorescent images
      revealed that the morphology of cells changed gradually from fusiform to round.
      High ROS levels were observed with high concentrations of [DPy]Br, indicating
      that [DPy]Br induced oxidative stress on S. obliquus. The SOD and CAT activities
      increased when the concentration was lower than IC50, whereas they decreased when
      the concentration was higher than IC50. The relative ROS content was
      significantly correlated with growth inhibition rate, cell membrane permeability,
      chlorophyll content, and SOD and CAT activities. The increase of ROS content in
      algal cells is an important toxicological mechanism of [DPy]Br to S. obliquus.

PMID- 29055583
TI  - Risk assessment for phthalate exposures in the elderly: A repeated biomonitoring
      study.
AB  - Recent studies indicated that exposure to phthalates affects the development of a
      variety of diseases in the elderly population. However, limited information was
      available about the variability of phthalate daily intakes (DIs) and the
      proportion of the population that is highly exposed to phthalates. Therefore, we
      measured the levels of three phthalate metabolites, mono-(2-ethyl-5-hydroxyhexyl)
      phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-n-butyl
      phthalate (MnBP) in 4014 urine samples repeatedly collected from 1646 elderly
      people. The DIs of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate
      (DnBP) were calculated using urinary MEHHP, MEOHP, and MnBP levels, and then the
      proportion of the population that was highly exposed to DEHP and DnBP was
      calculated. The intra-class correlation (ICC) for MEHHP, MEOHP, and MnBP levels
      was 0.07, 0.02, and 0.03, respectively, and exposures to DEHP and DnBP were
      strongly correlated with each other (correlation coefficient=0.89 and p
      value<0.0001). The geometric mean of estimated DI was 8.8MUg/kgbody-weight/day
      (range 0.005-3382.0) for DEHP and 1.5MUg/kgbody-weight/day (range 0.0002-1076.8)
      for DnBP. The percentages of urine samples with DEHP > reference dose (RfD,
      20MUg/kgbody-weight/day) and DnBP > tolerable daily intake (TDI, 10MUg/kgbody
      weight/day) were 20.2% and 3.6%, respectively. The Korean elderly were co-exposed
      to DEHP and DnBP, and the variation of DEHP and DnBP metabolite levels was mainly
      attributed to intra-individual variation, rather than inter-individual variation.
      Furthermore, Korean elderly were exposed to the hazards of DEHP and DnBP based on
      the high level of the exceedance rate over TDI or RfD for DEHP and DnBP. Since
      the elderly are very susceptible to environmental pollutants, the harmful effects
      of DEHP and DnBP in the elderly population should be further studied in the
      future.

PMID- 29055584
TI  - Nitrosomonas europaea adaptation to anoxic-oxic cycling: Insights from
      transcription analysis, proteomics and metabolic network modeling.
AB  - In suboxic or anoxic environments, nitrous oxide (N2O) can be produced by ammonia
      oxidizing bacteria (AOB) as a potent greenhouse gas. Although N2O producing
      inventory and pathways have been well-characterized using archetypal AOB, there
      is little known about their adaptive responses to oxic-anoxic cycling, which is a
      prevalent condition in soil, sediment, and wastewater treatment bioreactors. In
      this study, cellular responses of Nitrosomonas europaea 19718 to sustained anoxic
      oxic cycling in a chemostat bioreactor were evaluated at transcriptomic,
      proteomic, and fluxomic levels. During a single oxic-anoxic transition, the
      accumulations of major intermediates were found at the beginning of anoxia
      (nitric oxide, NO) and post anoxia (hydroxylamine, NH2OH, and N2O). Anoxic-oxic
      cycling over thirteen days led to significantly reduced accumulations of NH2OH,
      NO and N2O. Distinct from short-term responses, which were mostly regulated at
      the mRNA level, adapted cells seemed to sustain energy generation under repeated
      anoxia by partially sacrificing the NO detoxification capacities, and such
      adaptation was mainly regulated at the protein level. The proteomic data also
      suggested the potential contributions of the newly discovered cytochrome P460
      mediated NH2OH oxidation pathway to N2O productions. Flux balance analysis was
      performed based on a metabolic network model consisting of 49 biochemical
      reactions involved in nitrogen respiration, and changes in metabolic fluxes after
      the anoxic-oxic cycling were found to be better correlated with intracellular
      protein concentrations rather than mRNA levels. Previous studies focusing on
      single anoxic-oxic transition might have overlooked the adaptive responses of
      nitrifiers to anoxic-oxic cycling, and thus overestimated NO and N2O emission
      levels from natural and engineered nitrification systems.

PMID- 29055585
TI  - Ozone exposure- and flux-based response relationships with photosynthesis of
      winter wheat under fully open air condition.
AB  - Five winter wheat cultivars were exposed to ambient (A-O3) and elevated (E-O3,
      1.5 ambient) O3 in a fully open-air fumigation system in China. Ozone exposure-
      and flux based response relationships were established for seven physiological
      variables related to photosynthesis. The performance of the fitting of the
      regressions in terms of R2 increased when second order regressions instead of
      first order ones were used, suggesting that effects of O3 were more pronounced
      towards the last developmental stages of the wheat. The more robust indicators
      were those related with CO2 assimilation, Rubisco activity and RuBP regeneration
      capacity (Asat, Jmax and Vcmax), and chlorophyll content (Chl). Flux-based
      metrics (PODy, Phytotoxic O3 Dose over a threshold ynmolO3m-2s-1) predicted
      slightly better the responses to O3 than exposure metrics (AOTX, Accumulated O3
      exposure over an hourly Threshold of X ppb) for most of the variables. The best
      performance was observed for metrics POD1 (Asat, Jmax and Vcmax) and POD3 (Chl).
      For this crop, the proposed response functions could be used for O3 risk
      assessment based on physiological effects and also to include the influence of O3
      on yield or other variables in models with a photosynthetic component.

PMID- 29055586
TI  - No increase in marine microplastic concentration over the last three decades - A
      case study from the Baltic Sea.
AB  - Microplastic is considered a potential threat to marine life as it is ingested by
      a wide variety of species. Most studies on microplastic ingestion are short-term
      investigations and little is currently known about how this potential threat has
      developed over the last decades where global plastic production has increased
      exponentially. Here we present the first long-term study on microplastic in the
      marine environment, covering three decades from 1987 to 2015, based on a unique
      sample set originally collected and conserved for food web studies. We
      investigated the microplastic concentration in plankton samples and in digestive
      tracts of two economically and ecologically important planktivorous forage fish
      species, Atlantic herring (Clupea harengus) and European sprat (Sprattus
      sprattus), in the Baltic Sea, an ecosystem which is under high anthropogenic
      pressure and has undergone considerable changes over the past decades.
      Surprisingly, neither the concentration of microplastic in the plankton samples
      nor in the digestive tracts changed significantly over the investigated time
      period. Average microplastic concentration in the plankton samples was 0.21+/
      0.15particlesm-3. Of 814 fish examined, 20% contained plastic particles, of which
      95% were characterized as microplastic (<5mm) and of these 93% were fibres. There
      were no significant differences in the plastic content between species,
      locations, or time of day the fish were caught. However, fish size and
      microplastic in the digestive tracts were positively correlated, and the fish
      contained more plastic during summer than during spring, which may be explained
      by increased food uptake with size and seasonal differences in feeding activity.
      This study highlights that even though microplastic has been present in the
      Baltic environment and the digestive tracts of fishes for decades, the levels
      have not changed in this period. This underscores the need for greater
      understanding of how plastic is cycled through marine ecosystems. The stability
      of plastic concentration and contamination over time observed here indicates that
      the type and level of microplastic pollution may be more closely correlated to
      specific human activities in a region than to global plastic production and
      utilization as such.

PMID- 29055587
TI  - Preface for special issue, Ecotechnologies for Controlling Non-point Source
      Pollution and Protecting Aquatic Ecosystem (ENPE-2017).

PMID- 29055588
TI  - Contrasting effects of environmental change on the radial growth of co-occurring
      beech and fir trees across Europe.
AB  - Under predicted climate change, native silver fir (Abies alba) and European beech
      (Fagus sylvatica) are the most likely replacement species for the Norway spruce
      (Picea abies) monocultures planted across large parts of continental Europe. Our
      current understanding of the adaptation potential of fir-beech mixed forests to
      climate change is limited because long-term responses of the two species to
      environmental changes have not yet been comprehensively quantified. We compiled
      and analysed tree-ring width (TRW) series from 2855 dominant, co-dominant, sub
      dominant and suppressed fir and beech trees sampled in 17 managed and unmanaged
      mixed beech-fir forest sites across Continental Europe, including Bosnia and
      Herzegovina, Germany, Italy, Romania and Slovakia. Dendroecological techniques
      that combine various detrending methods were used to investigate variation in
      radial growth of co-occurring fir and beech trees. Coincidental with peak SO2
      emissions, the growth of silver fir declined between 1950 and 1980 at most sites,
      whereas beech growth increased during this period. Correspondent to a significant
      warming trend from 1990-2010, average beech growth declined, but silver fir
      growth increased. Long-term growth patterns and growth-climate sensitivity of fir
      and beech trees did not significantly differ between managed and unmanaged
      forests. Multi-decadal changes in the growth rate of all vertical tree classes
      were similar. In contrast to previous indications of limited drought
      susceptibility of beech mixed stands, this study suggests that the mixture of
      tree species in forest stands does not necessarily prevent growth depressions
      induced by long-term environmental change. Our results further imply that forest
      management does not necessarily alter their sensitivity to environmental changes.

PMID- 29055589
TI  - Potential linkage between sediment oxygen demand and pore water chemistry in weir
      impounded rivers.
AB  - Due to recent weir construction on four major rivers in South Korea, sediment has
      accumulated in the river bottom near the weirs, which has in turn raised concerns
      over the quality of overlying water. In this study, the seasonal and spatial
      variations of sediment oxygen demand (SOD) and the influencing factors were
      explored using pore water chemistry for the weir-impounded rivers. Muddy and
      sandy sediment samples were taken from 24 different sites along the four major
      rivers in summer and autumn, 2016. The SOD was measured in a laboratory based on
      10-hour incubation at in situ temperature. The measured pore water chemistry
      included the concentrations of dissolved organic carbon (DOC), total dissolved
      nitrogen (TDN), inorganic nitrogen (NH3-N, NO3-N, NO2-N), and phosphate
      phosphorous (PO4-P), and the optical properties from UV absorption spectra and
      fluorescence excitation-emission matrixes coupled with parallel factor analysis
      (EEM-PARAFAC). Significant differences in SOD values between muddy and sandy
      sediments were found only in summer (p=0.047). The higher SOD in summer versus
      autumn (p=0.015) was attributed to seasonal temperature differences. The higher
      NH3-N and the lower NO3-N of the pore water samples in summer versus autumn
      suggested that organic nitrogen decomposition via an ammonification and
      nitrification process could operate as an important factor for the SOD variations
      in summer and autumn, respectively. Principal component analysis revealed the
      mutual contributions of nitrogen-associated processes and the organic composition
      in pore water to increasing SOD levels. NH3-N in sediment pore water alone could
      be a good predictor for SOD. However, multiple regression analysis using NH3-N,
      fluorescence index and terrestrial humic-like components improved the estimation
      capability for SOD variations.

PMID- 29055590
TI  - Pharmaceutical biodegradation under three anaerobic redox conditions evaluated by
      chemical and toxicological analyses.
AB  - Biodegradation of pharmaceutically active compounds (PhACs) in the subsurface
      layer of constructed wetlands (CWs) under various anaerobic redox conditions is
      rarely studied. In this study, CW sediment microbial populations were enriched
      for PhAC biodegrading organisms. Biodegradation effectivity of a mixture of six
      PhACs (caffeine, CAF; naproxen, NAP; metoprolol, MET; propranolol, PRO;
      ibuprofen, IBP; carbamazepine, CBZ) and single compounds (CAF, NAP) was
      investigated under nitrate reducing, sulfate reducing, and methanogenic
      conditions using chemical and toxicological analyses. Biodegradation efficiencies
      varied strongly among the six PhACs and three redox conditions chosen. CAF and
      NAP were completely biodegraded under sulfate reducing and methanogenic
      conditions whereas biodegradation efficiencies of the other PhACs were much less
      (MET, PRO <20%; IBP, CBZ, negligible). CAF and NAP showed significantly lower
      biodegradation under nitrate reducing conditions than under the other two redox
      conditions. No difference was found in biodegradation efficiencies of CAF and NAP
      when present as single compound, or as a mixture with other PhACs. Different
      intermediates were observed, indicating different biodegradation pathways under
      different redox conditions and when the PhACs were present as single compound or
      in a mixture. From toxicological perspective, toxicity of PhACs and/or their
      intermediates to Vibrio fischeri was attenuated during the biodegradation
      process. Chemical and toxicological data showed positive correlations in
      principle component analysis, by which potentially toxic PhACs and intermediates
      are indicated for further ecotoxicological hazard assessment.

PMID- 29055591
TI  - Study of residual oil in Bay Jimmy sediment 5 years after the Deepwater Horizon
      oil spill: Persistence of sediment retained oil hydrocarbons and effect of
      dispersants on desorption.
AB  - The 2010 Deepwater Horizon (DwH) oil spill contaminated ~1,773km of the Gulf of
      Mexico shorelines. Yet, few field data are available on the long-term fate and
      persistency of sediment-retained oil. While an unprecedented amount of oil
      dispersants was applied, the effects of oil dispersants on desorption of field
      aged oil remain unknown. This study aimed to investigate the abundance,
      distributions and physico-chemical availability of the oil retained in Bay Jimmy
      sediment, Louisiana, five years after the DwH oil spill, and to determine the
      effects of two model oil dispersants on the desorption potential of the residual
      oil. Total petroleum hydrocarbons (TPHs), n-alkanes and polycyclic aromatic
      hydrocarbons (PAHs) in the sediment were analyzed and compared with those in the
      crude oil and the pre-DwH levels, and batch desorption kinetic tests were carried
      out to quantify the dispersant effects on the desorption rate and extent. The
      biomarker hopanes profile and diagnostic ratio were analyzed, which confirmed the
      origin and persistence of the sediment-retained oil. After five-year natural
      weathering, the oil level in the sediment remained orders of magnitude higher
      than the pre-spill level. Nearly all low-molecular-weight n-alkanes and 2-ring
      PAHs had been degraded. Oil dispersants, SPC 1000 and Corexit EC9500A, were able
      to enhance solubilization of the sediment-retained oil upon resuspension of the
      sediment. Successive desorption experiments indicated that 71.6% of TPHs, 74.8%
      of n-alkanes, and 91.9% of PAHs in the sediment remained highly stable and hardly
      desorbable by seawater; yet, addition of 18mg/L of SPC 1000 enhanced the
      desorption and lowered these fractions to 57.3%, 68.1%, and 81.4%, respectively.
      The findings are important for understanding the natural weathering rate and
      persistence of oil residual and the effects of dispersants on the physical and
      biological availabilities of aged oil in coastal sediments.

PMID- 29055592
TI  - Life cycle assessment of recycled concretes: A case study in southern Italy.
AB  - Concrete industry is responsible of the most significant contribution to the
      global warming due to the large amount of substances with environmental impacts
      produced during its entire life cycle (production process, construction,
      maintenance, dismantlement, and scrapping). The most important issue
      characterizing the concrete industry is related to the constant growth of
      consumption of natural aggregates. The purpose of the present research is to
      apply the standard protocol of life cycle assessment to 3 different concrete
      mixtures composed by wastes from construction and demolition (C&D), marble sludge
      and cement kiln dust (CDK) in order to compare the environmental and energy
      impacts. The main purpose is to analyze the potentials (capabilities/benefits) of
      recycled aggregate concrete. The proposed model analyses 37 recovery possible
      scenarios. The results were analyzed with the software SimaPro(c) and with the
      life cycle impact assessment method Eco Indicator 99. The results show how it is
      possible to decide for the optimal solution in order to reduce emissions and
      impacts due to the concrete production.

PMID- 29055593
TI  - Distribution of species and antimicrobial resistance among enterococci isolated
      from the fecal microbiota of captive blue-fronted parrot (Amazona aestiva) in Rio
      de Janeiro, Brazil.
AB  - Enterococcal strains recovered from fecal samples of captive blue-fronted parrots
      (Amazona aestiva) assisted at two wild animal screening centers in Rio de
      Janeiro, Brazil, were identified as Enterococcus hirae (the predominant species;
      75.3%), followed by Enterococcus faecalis (17.3%), Enterococcus casseliflavus
      (4.8%), Enterococcus gallinarum (1.7%), and Enterococcus hermanniensis (0.9%).
      All strains were susceptible to linezolid and teicoplanin. Rates of
      nonsusceptibility (including resistant and intermediate categories) to other 16
      antimicrobials tested varied from 69.3% to 0.4%, A considerable proportion
      (48.0%) of the strains was multidrug-resistant and diverse genetic determinants
      associated with antimicrobial resistance were identified. Tetracycline-resistant
      strains carried the tet(M) and/or tet(L) genes. Macrolides resistance was
      associated with the erm(B), erm(A) and mefA genes, while 43.2% of the isolates
      were negative for the investigated genes. High-level resistance to gentamicin
      associated with the aac(6')-le-aph(2")-la gene was detected in one E. faecalis
      strain. The two strains presenting high-level resistance to streptomycin were
      negative for the ant(6')-Ia, ant(3')-Ia, ant(9')-Ia and ant(9')-Ib genes. The
      vat(D) gene was found in all the 47 quinupristin/dalfopristin resistant strains
      identified as non-E. faecalis. Analysis of PFGE profiles of E. hirae strains
      after restriction with SmaI demonstrated the occurrence of five clonal groups.
      The predominant E. hirae clone was distributed among birds in the two
      institutions, suggesting that this clone was well adapted to the host and
      environments investigated. The four clonal groups identified among E. faecalis
      were composed by small numbers of strains and, generally, restricted to birds in
      the same sector. The occurrence of enterococcal strains exhibiting antimicrobial
      resistance traits and carrying genetic determinants that represent potential
      threats to the health of both humans and animals, in the intestinal microbiota of
      A. aestiva, highlights the need for additional monitoring studies to elucidate
      the population structure and the dynamics of transmission of these microorganisms
      among animals, humans and the environment.

PMID- 29055594
TI  - Effects of simulated nitrogen deposition on ectomycorrhizae community structure
      in hybrid larch and its parents grown in volcanic ash soil: The role of
      phosphorous.
AB  - With the rapid industrial development and modern agricultural practices,
      increasing nitrogen (N) deposition can cause nutrient imbalance in immature
      volcanic ash soil commonly found in Japan. Larch species, widely distributed in
      northeast Eurasia, are associated with ectomycorrhizal (ECM) fungi which play a
      critical role in nutrient acquisition for their hosts. In this study, we
      investigated species richness and diversity of ECM fungi associated with a hybrid
      larch (F1) and its parents, Dahurian larch (Larix gmelinii var. japonica) and
      Japanese larch (L. kaempferi), under simulated N deposition (0 and 100kgha-1yr-1)
      with/without phosphorous (P) (0 and 50kgha-1yr-1). Seedlings planted in immature
      volcanic ash with low nutrient availability were subjected to the N and P
      treatments for fifteen months. We found that response of ECM community structure
      to the increased nutrient availability depended on host genotypes. Nutrient
      addition significantly affected ECM structure in Japanese larch, but no such
      significant effect was found for Dahurian larch. Effects of the nutrient addition
      to ECM fungal community in F1 were intermediate. F1 was tolerant to high N
      loading, which was due to consistent, relatively high association with Suillus
      sp. and Hebeloma sp. F1 showed heterosis in relative biomass, which was most
      apparent under high N treatments. This co-variation of ECM fungal community
      structure and F1 biomass in response to N loading suggest that ECM community
      structure might play an important role in host growth. The present findings
      indicate effects of N deposition on ECM fungal community structure can depend on
      larch species, thus it is challenging to predict general trends.

PMID- 29055595
TI  - First use of a compound-specific stable isotope (CSSI) technique to trace
      sediment transport in upland forest catchments of Chile.
AB  - Land degradation is a problem affecting the sustainability of commercial forest
      plantations. The identification of critical areas prone to erosion can assist
      this activity to better target soil conservation efforts. Here we present the
      first use of the carbon-13 signatures of fatty acids (C14 to C24) in soil samples
      for spatial and temporal tracing of sediment transport in river bodies of upland
      commercial forest catchments in Chile. This compound-specific stable isotope
      (CSSI) technique was tested as a fingerprinting approach to determine the degree
      of soil erosion in pre-harvested forest catchments with surface areas ranging
      from 12 to 40ha. For soil apportionment a mixing model based on a Bayesian
      inference framework was used (CSSIAR v.2.0). Approximately four potential
      sediment sources were used for the calculations of all of the selected
      catchments. Unpaved forestry roads were shown to be the main source of sediment
      deposited at the outlet of the catchments (30-75%). Furthermore, sampling along
      the stream channel demonstrated that sediments were mainly comprised of sediment
      coming from the unpaved roads in the upper part of the catchments (74-98%). From
      this it was possible to identify the location and type of primary land use
      contributing to the sediment delivered at the outlet of the catchments. The
      derived information will allow management to focus efforts to control or mitigate
      soil erosion by improving the runoff features of the forest roads. The use of
      this CSSI technique has a high potential to help forestry managers and decision
      makers to evaluate and mitigate sources of soil erosion in upland forest
      catchments. It is important to highlight that this technique can also be a good
      complement to other soil erosion assessment and geological fingerprinting
      techniques, especially when attempting to quantify (sediment loads) and
      differentiate which type of land use most contributes to sediment accumulation.

PMID- 29055596
TI  - Combination of experimental and in silico methods for the assessment of the
      phototransformation products of the antipsychotic drug/metabolite Mesoridazine.
AB  - The lack of studies on the fate and effects of drug metabolites in the
      environment is of concern. As their parent compounds, metabolites enter the
      aquatic environment and are subject to biotic and abiotic process. In this
      regard, photolysis plays an important role. This study combined experimental and
      in silico quantitative structure-activity relationship (QSAR) methods to assess
      the fate and effects of Mesoridazine (MESO), a pharmacologically active human
      drug and metabolite of the antipsychotic agent Thioridazine, and its
      transformation products (TPs) formed through a Xenon lamp irradiation. After
      256min, the photodegradation of MESO?besylate (50mgL-1) achieved 90.4% and 6.9%
      of primary elimination and mineralization, respectively. The photon flux emitted
      by the lamp (200-600nm) was 169.55Jcm-2. Sixteen TPs were detected by means of
      liquid chromatography-high resolution mass spectrometry (LC-HRMS), and the
      structures were proposed based on MSn fragmentation patterns. The main
      transformation reactions were sulfoxidation, hydroxylation, dehydrogenation, and
      sulfoxide elimination. A back-transformation of MESO to Thioridazine was
      evidenced. Aerobic biodegradation tests (OECD 301 D and 301F) were applied to
      MESO and the mixture of TPs present after 256min of photolysis. Most of TPs were
      not biodegraded, demonstrating their tendency to persist in aquatic environments.
      The ecotoxicity towards Vibrio fischeri showed a decrease in toxicity during the
      photolysis process. The in silico QSAR tools QSARINS and US-EPA PBT profiler were
      applied for the screening of TPs with character of persistence, bioaccumulation,
      and toxicity (PBT). They have revealed the carbazole derivatives TP 355 and TP
      337 as PBT/vPvB (very persistent and very bioaccumulative) compounds. In silico
      QSAR predictions for mutagenicity and genotoxicity provided by CASE Ultra and
      Leadscope(r) indicated positive alerts for mutagenicity on TP 355 and TP 337.
      Further studies regarding the carbazole derivative TPs should be considered to
      confirm their hazardous character.

PMID- 29055597
TI  - Representativeness of environmental impact assessment methods regarding Life
      Cycle Inventories.
AB  - Life Cycle Assessment (LCA) characterises all the exchanges between human driven
      activities and the environment, thus representing a powerful approach for
      tackling the environmental impact of a production system. However, LCA
      practitioners must still choose the appropriate Life Cycle Impact Assessment
      (LCIA) method to use and are expected to justify this choice: impacts should be
      relevant facing the concerns of the study and misrepresentations should be
      avoided. This work aids practitioners in evaluating the adequacy between the
      assessed environmental issues and studied production system. Based on a
      geometrical standpoint of LCA framework, Life Cycle Inventories (LCIs) and LCIA
      methods were localized in the vector space spanned by elementary flows. A
      proximity measurement, the Representativeness Index (RI), is proposed to explore
      the relationship between those datasets (LCIs and LCIA methods) through an
      angular distance. RIs highlight LCIA methods that measure issues for which the
      LCI can be particularly harmful. A high RI indicates a close proximity between a
      LCI and a LCIA method, and highlights a better representation of the elementary
      flows by the LCIA method. To illustrate the benefits of the proposed approach,
      representativeness of LCIA methods regarding four electricity mix production LCIs
      from the ecoinvent database are presented. RIs for 18 LCIA methods (accounting
      for a total of 232 impact categories) were calculated on these LCIs and the
      relevance of the methods are discussed. RIs prove to be a criterion for
      distinguishing the different LCIA methods and could thus be employed by
      practitioners for deeper interpretations of LCIA results.

PMID- 29055598
TI  - Influence of humic substances and iron and aluminum ions on the sorption of
      acetamiprid to an arable soil.
AB  - Humic substances (HS) in soil and sediments, and surface water influence the
      behavior of organic xenobiotics in the environment. However, our knowledge of the
      effects of specific HS fractions, i.e., humic acids (HAs), fulvic acids (FAs),
      and humin (HM), on the sorption of organic xenobiotics is limited. The
      neonicotinoid insecticide acetamiprid is thought to contribute to the collapse of
      honeybee colonies. To understand the role that soil organic matter plays in the
      fate of acetamiprid, interactions between acetamiprid and the above HS fractions
      were examined. Batch experiments were conducted using various combinations of a
      field soil sample and the above 3 HS fractions prepared from the same soil, and
      differences in isotherm values for acetamiprid sorption were investigated based
      on the structural differences among the HS fractions. The sorption of acetamiprid
      to soil minerals associated with HM (MHM) (Freundlich isotherm constant, Kf:
      6.100) was reduced when HAs or FAs were added (Kf: 4.179 and 4.756,
      respectively). This can be attributed to hydrophobic interactions between HM and
      HAs or FAs in which their dissociated carboxyl and phenolic groups become
      oriented to face the soil solution. The amount of acetamiprid that was adsorbed
      to (MHM+HA) or (MHM+FA) increased when aluminum ions were added (Kf: 6.933 and
      10.48, respectively), or iron ions were added (Kf: 7.303 and 11.29,
      respectively). Since acetamiprid has no affinity for inorganic components in
      soil, the formation of HS-metal complexes by cation bridging may have oriented
      the hydrophobic moieties in the HAs or FAs to face the soil solution and may also
      have resulted in the formation of dense structures, resulting in an increase in
      the amount of acetamiprid that becomes adsorbed to these structures. These
      results highlight the importance of interactions among soil components in the
      pedospheric diffusion of acetamiprid.

PMID- 29055599
TI  - Drainage and fertilization effects on nutrient availability in an ombrotrophic
      peatland.
AB  - Nutrient availability is an important control on the vegetation distribution,
      productivity and functioning of peatland ecosystems and we examined spatial and
      temporal patterns of nutrient availability through ion exchange at Mer Bleue bog,
      southeast Ontario, Canada. We installed ion exchange probes at 5-15cm for 4weeks
      and determined nutrient sorption at undisturbed sites as well as those affected
      by nitrogen (N), phosphorus (P), potassium (K) fertilization and drainage. Under
      undisturbed conditions, the bog had very small amount of available nutrients,
      especially N (ammonium>nitrate) and P, and exhibited small variations in nutrient
      availability during the growing season (May to October). The increase in NPK
      availability upon fertilization was short-lived over the season and the
      stoichiometry of available NPK captured by the probes was mismatched with the
      vegetation. The increase in nutrient availability with drainage was confounded by
      substantial changes in vegetation. We compare these results with data from other
      Canadian bogs and fens to provide baseline data on nutrient availability in
      peatlands.

PMID- 29055601
TI  - Restoration of a denser myocardial capillary network after mechanical unloading
      of failing hearts in children with dilated cardiomyopathy.

PMID- 29055600
TI  - Prevalence of polyreactive innate clones among graft--infiltrating B cells in
      human cardiac allograft vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) has been associated with graft
      infiltrating B cells, although their characteristics are still unclear. In this
      study we examined the frequency, localization and reactivity profile of graft
      infiltrating B cells to determine their contribution to the pathophysiology of
      CAV. METHODS: B cells, plasma cells and macrophages were examined by
      immunohistochemistry in 56 allografts with CAV, 49 native failed hearts and 25
      autopsy specimens. A total of 102 B-cell clones were immortalized directly from
      the infiltrates of 3 fresh cardiac samples with CAV. Their secreted antibodies
      were assessed using enzyme-linked immunoassay and flow cytometry. RESULTS: B-cell
      infiltration was observed around coronary arteries in 93% of allograft explants
      with CAV. Comparatively, intragraft B cells were less frequent and less dense in
      the intraventricular myocardium from where routine biopsies are obtained. Plasma
      cells and macrophages were also detected in 85% and 95% of explants,
      respectively. Remarkably, B-cell infiltrates were not associated with circulating
      donor-specific antibodies (DSA) or prior episodes of antibody-mediated rejection
      (AMR). Among all B-cell clones generated from 3 explants with CAV, a majority
      secreted natural antibodies reactive to multiple autoantigens and apoptotic
      cells, a characteristic of innate B cells. CONCLUSIONS: Our study reveals a high
      frequency of infiltrating B cells around the coronary arteries of allografts with
      CAV, independent of DSA or AMR. These cells are enriched for innate B cells with
      a polyreactive profile. The findings shift the focus from conventional DSA
      producing B cells to the potentially pathogenic polyreactive B cells in the
      development of clinical CAV.

PMID- 29055602
TI  - Late graft dysfunction after pediatric heart transplantation is associated with
      fibrosis and microvasculopathy by automated, digital whole-slide analysis.
AB  - BACKGROUND: Histopathologic features of late graft dysfunction (LGD) in
      endomyocardial biopsies (EMBs) after pediatric heart transplantation (HT) have
      been incompletely described and rarely quantified. We employed automated,
      morphometric analysis of whole-slide EMB images to objectively quantify fibrosis
      and microvasculopathy after pediatric HT. METHODS: Nine recipients with clinical
      LGD were matched with controls on age, listing diagnosis, crossmatch and time
      since HT. Fibrosis was quantified as percent tissue area with fibrosis and
      capillary density as capillaries per unit area, number of capillary "neighbors"
      within 30 MUm of each myocyte and myocyte-to-nearest-capillary diffusion
      distance. Clinical data, including all EMB reports, were also reviewed. RESULTS:
      The groups were well matched for age at HT (median 4.0 vs 3.1 years), listing
      diagnosis (50% congenital heart disease for each), positive crossmatch (11% each)
      and days post-HT (2,628 vs 2,894, p = 0.69). Despite a similar number of previous
      EMBs (median 23 each, p = 0.43), areas occupied by fibrosis were greater in LGD
      cases (44.5% vs 23.2%, p = 0.012). Capillary number/area data were not
      statistically different between LGD cases and controls (378/mm2 vs 559/mm2, p =
      0.57), but LGD cases more commonly had zero capillary neighbors (35% vs 20%, p =
      0.02) and greater myocyte-to-nearest-capillary distances (27.1 MUm vs 18.7 MUm, p
      = 0.005). Cumulative rejection history correlated with fibrosis (r = 0.49, p =
      0.039) and myocyte-to-nearest-capillary distance (r = 0.5, p = 0.036).
      CONCLUSIONS: LGD after pediatric HT is associated with previous rejection and
      characterized histologically by fibrosis and microvasculopathy, which are not
      readily appreciated by traditional semi-quantitative EMB analysis. Software
      assisted EMB analysis may enable greater pathophysiologic understanding of LGD
      and identification of targets for future study and intervention.

PMID- 29055604
TI  - Treatment of primary graft dysfunction after lung transplantation with orally
      inhaled AP301: A prospective, randomized pilot study.
AB  - BACKGROUND: Primary graft dysfunction (PGD) after lung transplantation (LTx)
      carries significant morbidity and mortality in the early post-operative period
      and is associated with the development of chronic lung allograft dysfunction.
      AP301, an activator of epithelial sodium channel-mediated Na+ uptake represents a
      new concept for prevention and treatment of pulmonary edema and has shown
      promising results in the pre-clinical setting. This pilot study investigated the
      clinical effect of inhaled AP301 on patients with development of PGD > 1
      according to International Society of Heart and Lung Transplantation criteria
      after primary LTx in a high-volume center and was conducted as a randomized,
      placebo-controlled, single-center pilot-study including 20 patients. All
      consecutive patients fulfilling inclusion criteria were screened for PGD at
      arrival on the intensive care unit (ICU) after LTx. After randomization, inhaled
      AP301 or placebo was administered by nebulizer twice daily for 7 days or until
      extubation. Otherwise, patients were treated according to routine clinical
      protocol. Partial pressure of arterial oxygen (Pao2)/fraction of inspired oxygen
      (Fio2) values were obtained until extubation and assessed as a primary outcome
      parameter. Patients were monitored for 30 days within the study protocol.
      RESULTS: From July 2013 to August 2014, 20 patients were randomized 1:1 to AP301
      (Group 1) or placebo (Group 2). Both groups were comparable with regard to sex
      (40% women/60% men vs 50% women/50% men), mean age (55 +/- 13 vs 54 +/- 6 years),
      comorbidities, and diagnosis leading to LTx. The Pao2/Fio2 ratio at the time of
      inclusion was comparable in both groups, with a mean 235.65 +/- 90.78 vs 214.2 +/
      95.84 (p = 0.405), and there was no significant difference in the extravascular
      lung water index (13.88 +/- 5.28 vs 16 +/- 6.29 ml/kg, p = 0.476). The primary
      end point was mean Pao2/Fio2 ratio values between baseline and Day 3. In the
      AP301 group, only 1 patient was ventilated at Day 4 and no patients were
      ventilated after Day 4. In the placebo group, 5 patients were ventilated on Day 4
      and 2 patients on Days 5, 6, and 7. The mean increase in the Pao2/Fio2 ratio was
      significantly higher in Group 1 patients, and the mean between baseline and at 72
      hours was 365.6 +/- 90.4 in Group 1 vs 335.2 +/- 42.3 in Group 2 (p = 0.049). The
      duration of intubation was shorter in Group 1 than in Group 2 patients (2 +/-
      0.82 vs 3.7 +/- 1.95 days; p = 0.02). ICU stay was 7.5 +/- 3.13 days in Group 1
      vs 10.8 +/- 8.65 days in group 2 (p = 0.57). Survival at 30 days was 100%. No
      severe adverse events were recorded. CONCLUSIONS: This study was designed as a
      proof-of-concept pilot study. Although it was not powered to achieve statistical
      significances, the study demonstrated relevant clinical effects of inhaled AP301
      on patients with PGD after primary LTx. The improved gas exchange led to a
      significantly shorter duration of mechanical ventilation and a trend towards a
      shorter ICU stay. Further investigation of AP301 for treatment of PGD in larger
      studies is warranted. TRIAL REGISTRATION: The trial is registered at
      https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000716-21/AT.

PMID- 29055603
TI  - End-stage renal disease after pediatric heart transplantation: A 25-year national
      cohort study.
AB  - BACKGROUND: End-stage renal disease (ESRD), defined as the need for chronic
      dialysis and/or kidney transplantation (KTx), is a known complication after heart
      transplant (HTx). However, factors associated with ESRD are not well elucidated.
      The objectives of this study were to determine the prevalence, risk factors, and
      outcomes associated with ESRD after pediatric HTx. METHODS: Scientific Registry
      of Transplant Recipients data were linked, using direct identifiers, to the
      United States Renal Data System to identify patients (aged <= 18 years) who
      underwent primary HTx between 1989 and 2013. Risk factors for ESRD and death were
      analyzed using Cox regression analysis. RESULTS: Combining the above 2 databases
      identified ~25% additional HTx patients who developed ESRD that were not captured
      by either database alone. During a median follow-up of 11.8 years, ESRD developed
      in 276 of 6,901 patients (4%). The actuarial risk of developing ESRD after HTx
      was 3% at 10 years and 16% at 20 years. Age at HTx > 1 year, African-American
      race, year of HTx before 2000, hypertension, diabetes mellitus, re-HTx, acute
      dialysis, graft failure, and hospitalized infection were significant risk factors
      for ESRD development. Those who remained on chronic dialysis had higher risk of
      death than those who received KTx (hazard ratio, 31.4; 95% confidence interval,
      20.8-48.4; p < 0.0001). CONCLUSIONS: ESRD after pediatric HTx is more prevalent
      in HTx survivors than documented by a transplant database alone. A number of
      factors develop at or after HTx that increase the risk for developing ESRD. Use
      of KTx in post-HTx ESRD is associated with improved survival.

PMID- 29055605
TI  - Capacity for Cancer Care Delivery Research in National Cancer Institute Community
      Oncology Research Program Community Practices: Availability of Radiology and
      Primary Care Research Partners.
AB  - PURPOSE: Cancer care spans the spectrum from screening and diagnosis through
      therapy and into survivorship. Delivering appropriate care requires patient
      transitions across multiple specialties, such as primary care, radiology, and
      oncology. From the program's inception, the National Cancer Institute Community
      Oncology Research Program (NCORP) sites were tasked with conducting cancer care
      delivery research (CCDR) that evaluates structural, organizational, and social
      factors, including care transitions that determine patient outcomes. The aim of
      this study is to describe the capacity of the NCORP to conduct multidisciplinary
      CCDR that includes radiology and primary care practices. METHODS: The NCORP
      includes 34 community and 12 minority and underserved community sites. The
      Landscape Capacity Assessment was conducted in 2015 across these 46 sites,
      composed of the 401 components and subcomponents designated to conduct CCDR. Each
      respondent had the opportunity to designate an operational practice group,
      defined as a group of components and subcomponents with common care practices and
      resources. The primary outcomes were the proportion of adult oncology practice
      groups with affiliated radiology and primary care practices. The secondary
      outcomes were the proportion of those affiliated radiology and primary care
      groups that participate in research. RESULTS: Eighty-seven percent of components
      and subcomponents responded to at least some portion of the assessment,
      representing 230 practice groups. Analyzing the 201 adult oncology practice
      groups, 85% had affiliated radiologists, 69% of whom participate in research.
      Seventy-nine percent had affiliated primary care practitioners, 31% of whom
      participate in research. Institutional size, multidisciplinary group practice,
      and ownership by large regional or multistate health systems was associated with
      research participation by affiliated radiology and primary care groups. Research
      participation by these affiliated specialists was not significantly different
      between the community and the minority and underserved community sites.
      CONCLUSIONS: Research relationships exist between the majority of community
      oncology sites and affiliated radiology practices. Research relationships with
      affiliated primary care practices lagged. NCORP as a whole has the opportunity to
      encourage continued and expanded engagement where relationships exist. Where no
      relationship exists, the NCORP can encourage recruitment, particularly of primary
      care practices as partners.

PMID- 29055606
TI  - Carlson's Law and the Power of Frontline Innovation.

PMID- 29055607
TI  - Testifying on Legislation: A Primer for the Inexperienced Radiologist.

PMID- 29055608
TI  - Qualitative Study to Understand Ordering of CT Angiography to Diagnose Pulmonary
      Embolism in the Emergency Room Setting.
AB  - PURPOSE: To better understand the decision making behind the ordering of CT
      pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism (PE) in the
      emergency department. METHODS: We conducted semistructured interviews with our
      institution's emergency medicine (EM) providers and radiologists who read CTPAs
      performed in the emergency department. We employed the Theoretical Domains
      Framework-a formal, structured approach used to better understand the motivations
      and beliefs of physicians surrounding a complex medical decision making-to
      categorize the themes that arose from our interviews. RESULTS: EM providers were
      identified as the main drivers of CTPA ordering. Both EM and radiologist groups
      perceived the radiologist's role as more limited. Experience- and gestalt-based
      heuristics were the most important factors driving this decision and more
      important, in many cases, than established algorithms for CTPA ordering. There
      were contrasting views on the value of d-dimer in the suspected PE workup, with
      EM providers finding this test less useful than radiologists. EM provider and
      radiologist suggestions for improving the appropriateness of CTPA ordering
      consisted of making this process more arduous and incorporating d-dimer tests and
      prediction rules into a decision support tool. CONCLUSION: EM providers were the
      main drivers of CTPA ordering, and there was a marginalized role for the
      radiologist. Experience- and gestalt-based heuristics were the main influencers
      of CTPA ordering. Our findings suggest that a more nuanced intervention than
      simply including a d-dimer and a prediction score in each preimaging workup may
      be necessary to curb overordering of CTPA in patients suspected of PE.

PMID- 29055609
TI  - From Academia to Government to Industry: A Strange Journey and Its Lessons.

PMID- 29055610
TI  - Transition From Peer Review to Peer Learning: Experience in a Radiology
      Department.
AB  - PURPOSE: To describe the process by which a radiology department moved from peer
      review to peer collaborative improvement (PCI) and review data from the first 16
      months of the PCI process. MATERIALS AND METHODS: Data from the first 16 months
      after PCI were reviewed: number of case reviews performed, number of learning
      opportunities identified, percentage yield of learning opportunities identified,
      type of learning opportunities identified, and comparison of the previous
      parameters between case randomly reviewed versus actively pushed (issues actively
      identified and entered). Changes in actively pushed cases were also assessed as
      volume per month over the 16 months (run chart). Faculty members were surveyed
      about their perception of the conversion to PCI. RESULTS: In all, 12,197 cases
      were peer reviewed, yielding 1,140 learning opportunities (9.34%). The most
      common types of learning opportunities for all reviewed cases included perception
      (5.1%) and reporting (1.9%). The yield of learning opportunities from actively
      pushed cases was 96.3% compared with 3.88% for randomly reviewed cases. The
      number of actively pushed cases per month increased over the course of the period
      and established two new confidence intervals. The faculty survey revealed that
      the faculty perceived the new PCI process as positive, nonpunitive, and focused
      on improvement. CONCLUSIONS: The study demonstrates that a switch to PCI is
      perceived as nonpunitive and associated with increased radiologist submission of
      learning opportunities. Active entering of identified learning opportunities had
      a greater yield and perceived value, compared with random review of cases.

PMID- 29055612
TI  - The relationship between fibrinogen and in-hospital mortality in patients with
      type A acute aortic dissection.
AB  - BACKGROUND AND PURPOSE: Fibrinogen plays an important role in hemostasis and
      thrombosis and is proven to have prognostic significance in patients with
      cardiovascular disease. We examined the utility of fibrinogen as a prognostic
      indicator for patients with type A acute aortic dissection (AAD). METHODS: This
      study was performed in consecutive patients with type A AAD admitted to our
      hospital within 24 hours after onset of symptoms. Fibrinogen levels were measured
      on admission. Baseline clinical characteristics and laboratory test results were
      collected. The endpoint was in-hospital mortality. RESULTS: A total of 143
      patients with type A AAD were enrolled. Compared with the survivors, the
      nonsurvivors had significant lower fibrinogen levels (1.95(1.37, 2.38) vs.
      2.37(1.85, 3.15) g/L, p=0.001). The cutoff level of fibrinogen determined by ROC
      curve analysis was 2.17 g/L, with a sensitivity, specificity of 71.9%, 60.4%
      respectively, and the area under the ROC curve was 0.686 (95% CI, 0.585-0.768;
      p=0.001). After controlling for potentially relevant confounding variables, we
      found an admission fibrinogen level less than 2.17g/L was associated with an
      increased risk of in-hospital mortality (odds ratio, 5.527; 95% CI, 1.660-18.401;
      p=0.005) compared with those with fibrinogen greater than 2.17g/L. CONCLUSION:
      Low fibrinogen level on admission is an independent predictor of in-hospital
      mortality in patients with type A AAD.

PMID- 29055611
TI  - Mobile Versus Fixed Facility: Latinas' Attitudes and Preferences for Obtaining a
      Mammogram.
AB  - PURPOSE: Mobile mammographic services have been proposed as a way to reduce
      Latinas' disproportionate late-stage presentation compared with white women by
      increasing their access to mammography. The aims of this study were to assess why
      Latinas may not use mobile mammographic services and to explore their preferences
      after using these services. METHODS: Using a mixed-methods approach, a secondary
      analysis was conducted of baseline survey data (n = 538) from a randomized
      controlled trial to improve screening mammography rates among Latinas in
      Washington. Descriptive statistics and bivariate regression were used to
      characterize mammography location preferences and to test for associations with
      sociodemographic indices, health care access, and perceived breast cancer risk
      and beliefs. On the basis of these findings, a qualitative study (n = 18) was
      used to explore changes in perceptions after using mobile mammographic services.
      RESULTS: More Latinas preferred obtaining a mammogram at a fixed facility (52.3%
      [n = 276]) compared with having no preference (46.3% [n = 249]) and preferring
      mobile mammographic services (1.7% [n = 9]). Concerns about privacy and comfort
      (15.6% [n = 84]) and about general quality (10.6% [n = 57]) were common reasons
      for preferring a fixed facility. Those with no history of mammography preferred a
      fixed facility (P < .05). In the qualitative study, Latinas expressed similar
      initial concerns but became positive toward the mobile mammographic services
      after obtaining a mammogram. CONCLUSIONS: Although most Latinas preferred
      obtaining a mammogram at a fixed facility, positive experiences with mobile
      mammography services changed their attitudes toward them. These findings
      highlight the need to include community education when using mobile mammographic
      service to increase screening mammography rates in underserved communities.

PMID- 29055613
TI  - Which transfers can we avoid: Multi-state analysis of factors associated with
      discharge home without procedure after ED to ED transfer for traumatic injury.
AB  - OBJECTIVE: Among injured patients transferred from one emergency department (ED)
      to another, we determined factors associated with being discharged from the
      second ED without procedures, or admission or observation. METHODS: We analyzed
      all patients with injury diagnosis codes transferred between two EDs in the 2011
      Healthcare Utilization Project State Emergency Department and State Inpatient
      Databases for 6 states. Multivariable hierarchical logistic regression evaluated
      the association between patient (demographics and clinical characteristics) and
      hospital factors, and discharge from the second ED without coded procedures.
      RESULTS: In 2011, there were a total of 48,160 ED-to-ED injury transfers, half of
      which (49%) were transferred to non-trauma centers, including 23% with major
      trauma. A total of 22,011 transfers went to a higher level of care, of which 36%
      were discharged from the ED without procedures. Relative to torso injuries,
      discharge without procedures was more likely for patients with soft tissue (OR
      6.8, 95%CI 5.6-8.2), head (OR 3.7, 95%CI 3.1-4.6), facial (OR 3.8, 95%CI 3.1
      4.7), or hand (OR 3.1, 95%CI 2.6-3.8) injuries. Other factors included Medicaid
      (OR 1.3, 95%CI 1.2-1.5) or uninsured (OR 1.3, 95%CI 1.2-1.5) status. Treatment at
      the receiving ED added an additional $2859 on average (95% CI $2750-$2968) per
      discharged patient to the total charges for injury care, not including the costs
      of ambulance transport between facilities. CONCLUSION: Over a third of patients
      transferred to another ED for traumatic injury are discharged from the second ED
      without admission, observation, or procedures. Telemedicine consultation with sub
      specialists might reduce some of these transfers.

PMID- 29055614
TI  - The RTS plus measurement of the RDW improves the prediction of 28-day mortality
      in trauma patients.

PMID- 29055616
TI  - Sizing capacity levels in emergency medical services dispatch centers: Using the
      newsvendor approach.
AB  - BACKGROUND: The increased volume in demand worldwide in the present day has led
      to the need for the establishment of effective ambulance services. As call
      centers have become the primary contact point between patients and emergency
      service providers, the planning of the call center has become a key task for
      administrators. OBJECTIVES: The aim of this study is to apply a widely used
      operations management method, the newsvendor model, for optimizing the capacity
      level in EMS call centers with a minimum cost in order to efficiently meet the
      calls arriving. METHODS: Real-life data from a call center for ambulance services
      in a major city in Turkey was used. We propose using the newsvendor model for
      optimizing this call center's capacity level based on the forecasts of periodic
      call volumes via basic methods. RESULTS: Ambulance service call volumes vary
      during the day and weekday call profiles are different from weekends. By
      separating the analysis into weekdays and weekends and illustrating shorter time
      intervals within the days, call volume can be forecast. Taking not only the point
      forecast but also the variation of the forecast into account, the capacity level
      of each period can be planned in a cost-effective way. CONCLUSIONS: This paper
      provides a basis for operation planning strategies of ambulance services by
      reconsidering the uncertainties of demand. The newsvendor model, which works well
      under parameter uncertainty, can be used in planning the capacities of health
      care services, especially when high service levels are required.

PMID- 29055615
TI  - Achieving ventricular rate control in patients taking chronic beta-blocker
      therapy.
AB  - STUDY OBJECTIVE: The objective of this study is to evaluate the difference in
      response to ventricular rate control with intravenous (IV) metoprolol compared to
      IV diltiazem in patients taking chronic beta-blocker therapy who present to the
      emergency department (ED) in atrial fibrillation (AF) with rapid ventricular rate
      (RVR). METHODS: This was a single-center, retrospective study of adult patients
      taking chronic oral metoprolol. Chronic metoprolol therapy was defined as
      patients prescribed and taking oral metoprolol within 5days of study inclusion.
      Rate control was defined as either a decrease in ventricular rate<100bpm or
      <120bpm if the decrease was at least 20% from the presenting heart rate. RESULTS:
      A total of 332 patients were included, with 16 patients in the IV diltiazem group
      and 316 patients in the IV metoprolol group. In the diltiazem arm, 68.8% of
      patients achieved successful rate control compared to 42.4% of patients in the
      metoprolol group (p=0.067). Treatment with IV metoprolol resulted in more
      hospital admissions (58% vs. 6.25% with diltiazem, p<0.001). Treatment with
      diltiazem was associated with a greater incidence of bradycardia compared to IV
      metoprolol (13% vs. 0%, p=0.002). CONCLUSIONS: The use of IV diltiazem was
      associated with a higher rate of successful response to rate control compared to
      IV metoprolol in patients in AF with RVR on chronic beta-blocker therapy, however
      the difference between groups was not statistically significant.

PMID- 29055618
TI  - CPR skill retention in 795 high school students following a 45-minute course with
      psychomotor practice.

PMID- 29055617
TI  - Qualitative and quantitative radiological analysis of non-contrast CT is a strong
      indicator in patients with acute pyelonephritis.
AB  - OBJECTIVE: To evaluate the performance of non-contrast computed tomography (CT)
      by reporting the difference in attenuation between normal and inflamed renal
      parenchyma in patients clinically diagnosed with acute pyelonephritis (APN).
      MATERIAL AND METHODS: This is a retrospective study concerned with non-contrast
      CT evaluation of 74 patients, admitted with a clinical diagnosis of APN and
      failed to respond to 48h antibiotics treatment. Mean attenuation values in
      Hounsfield units (HU) were measured in the upper, middle and lower segments of
      the inflamed and the normal kidney of the same patient. Independent t-test was
      performed for statistical analysis. Image evaluation included receiver operating
      characteristic (ROC), visual grading characteristic (VGC) and kappa analyses.
      RESULTS: The mean attenuation in the upper, middle and lower segments of the
      inflamed renal cortex was 32%, 25%, and 29% lower than the mean attenuation of
      the corresponding cortical segments of the contralateral normal kidney,
      respectively (p<0.01). The mean attenuation in the upper, middle, and lower
      segments of the inflamed renal medulla was 48%, 21%, and 30%, lower than the mean
      attenuation of the corresponding medullary segments of the contralateral normal
      kidney (p<0.02). The mean attenuation between the inflamed and non-inflamed renal
      cortex and medulla was 29% and 30% lower respectively (p<0.001). The AUCROC
      (p<0.001) analysis demonstrated significantly higher scores for pathology
      detection, irrespective of image quality, compared to clinical and laboratory
      results with an increased inter-reader agreement from poor to substantial.
      CONCLUSION: Non-contrast CT showed a significant decrease in the parenchymal
      density of the kidney affected with APN in comparison to the contralateral normal
      kidney of the same patient. This can be incorporated in the diagnostic criteria
      of APN in NCCT in the emergency setting.

PMID- 29055619
TI  - A Cornucopia of Therapies under Study for Hemophilia.

PMID- 29055621
TI  - Adipose Stem Cell Therapy for Chronic Pancreatitis.

PMID- 29055622
TI  - E pluribus unum: Combining Molecular Strategies to Defeat Head and Neck Cancer.

PMID- 29055620
TI  - Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and
      Unique Humoral Seroreactivity.
AB  - Existing recombinant adeno-associated virus (rAAV) serotypes for delivering in
      vivo gene therapy treatments for human liver diseases have not yielded combined
      high-level human hepatocyte transduction and favorable humoral neutralization
      properties in diverse patient groups. Yet, these combined properties are
      important for therapeutic efficacy. To bioengineer capsids that exhibit both
      unique seroreactivity profiles and functionally transduce human hepatocytes at
      therapeutically relevant levels, we performed multiplexed sequential directed
      evolution screens using diverse capsid libraries in both primary human
      hepatocytes in vivo and with pooled human sera from thousands of patients. AAV
      libraries were subjected to five rounds of in vivo selection in xenografted mice
      with human livers to isolate an enriched human-hepatotropic library that was then
      used as input for a sequential on-bead screen against pooled human
      immunoglobulins. Evolved variants were vectorized and validated against existing
      hepatotropic serotypes. Two of the evolved AAV serotypes, NP40 and NP59,
      exhibited dramatically improved functional human hepatocyte transduction in vivo
      in xenografted mice with human livers, along with favorable human seroreactivity
      profiles, compared with existing serotypes. These novel capsids represent
      enhanced vector delivery systems for future human liver gene therapy
      applications.

PMID- 29055623
TI  - Targeting of Cell Surface Proteolysis of Collagen XVII Impedes Squamous Cell
      Carcinoma Progression.
AB  - Squamous cell carcinoma (SCC) is one of the most common skin cancers and causes
      significant morbidity. Although the expression of the epithelial adhesion
      molecule collagen XVII (ColXVII) has been linked to SCC invasion, only little is
      known about its mechanistic contribution. Here, we demonstrate that ColXVII
      expression is essential for SCC cell proliferation and motility. Moreover, it
      revealed that particularly the post-translational modification of ColXVII by
      ectodomain shedding is the major driver of SCC progression, because ectodomain
      selective immunostaining was mainly localized at the invasive front of human
      cutaneous SCCs, and exclusive expression of a non-sheddable ColXVII mutant in SCC
      25 cells inhibits their matrix-independent growth and invasiveness. This cell
      surface proteolysis, which is strongly elevated during SCC invasion and
      metastasis, releases soluble ectodomains and membrane-anchored endodomains. Both
      released ColXVII domains play distinct roles in tumor progression: the endodomain
      induces proliferation and survival, whereas the ectodomain accelerates
      invasiveness. Furthermore, specific blockage of shedding by monoclonal ColXVII
      antibodies repressed matrix-independent growth and invasion of SCC cells in
      organotypic co-cultures. Thus, selective inhibition of ColXVII shedding may offer
      a promising therapeutic strategy to prevent SCC progression.

PMID- 29055624
TI  - Geriatric assessment and biomarkers in patients with metastatic breast cancer
      receiving first-line mono-chemotherapy: Results from the randomized phase III
      PELICAN trial.
AB  - OBJECTIVES: To determine predictive/prognostic factors for patients with
      metastatic breast cancer (MBC) receiving first-line monochemotherapy using
      biomarker analysis and geriatric assessment (GA). MATERIALS AND METHODS:
      Karnofsky Performance Status (KPS) and GA as clinical parameters, and prognostic
      inflammatory and nutritional index (PINI), and Glasgow prognostic score (GPS) as
      biomarkers were analyzed for association with clinical outcome within the
      randomized phase III PEg-LIposomal Doxorubicin vs. CApecitabin iN MBC (PELICAN)
      trial of first-line pegylated liposomal doxorubicin (PLD) or capecitabine.
      RESULTS: Of 210 patients, 38% were >65years old. GA (n=152) classified 74% as
      fit, 10% as compromised, and 16% as frail. Biomarkers showed no age dependency.
      In multivariate analysis (n=70) KPS, GA, cumulative illness rating scale
      geriatrics (CIRS-G), and GPS were significantly associated with time to
      progression, and KPS, CIRS-G, and instrumental activities of daily living (IADL)
      from GA, and PINI showed a significant correlation with overall survival.
      CONCLUSION: GA evaluation was feasible. KPS significantly correlated with
      efficacy outcomes. Items of a GA and biomarkers of inflammation and nutrition may
      have prognostic significance in patients with MBC.

PMID- 29055625
TI  - Coronary Artery Calcium Progression Is Associated With Coronary Plaque Volume
      Progression: Results From a Quantitative Semiautomated Coronary Artery Plaque
      Analysis.
AB  - OBJECTIVES: The aim of this study was to determine whether coronary artery
      calcium (CAC) progression was associated with coronary plaque progression on
      coronary computed tomographic angiography. BACKGROUND: CAC progression and
      coronary plaque characteristics are associated with incident coronary heart
      disease. However, natural history of coronary atherosclerosis has not been well
      described to date, and the understanding of the association between CAC
      progression and coronary plaque subtypes such as noncalcified plaque progression
      remains unclear. METHODS: Consecutive patients who were referred to our clinic
      for evaluation and had serial coronary computed tomography angiography scans
      performed were included in the study. Coronary artery plaque (total, fibrous,
      fibrous-fatty, low-attenuation, densely calcified) volumes were calculated using
      semiautomated plaque analysis software. RESULTS: A total of 211 patients (61.3 +/
      12.7 years of age, 75.4% men) were included in the analysis. The mean interval
      between baseline and follow-up scans was 3.3 +/- 1.7 years. CAC progression was
      associated with a significant linear increase in all types of coronary plaque and
      no plaque progression was observed in subjects without CAC progression. In
      multivariate analysis, annualized and normalized total plaque (beta = 0.38; p <
      0.001), noncalcified plaque (beta = 0.35; p = 0.001), fibrous plaque (beta =
      0.56; p < 0.001), and calcified plaque (beta = 0.63; p = 0.001) volume
      progression, but not fibrous-fatty (beta = 0.03; p = 0.28) or low-attenuation
      plaque (beta = 0.11; p = 0.1) progression, were independently associated with CAC
      progression. Plaque progression did not differ between the sexes. A significantly
      increased total and calcified plaque progression was observed in statin users.
      CONCLUSIONS: In a clinical practice setting, progression of CAC was significantly
      associated with an increase in both calcified and noncalcified plaque volume,
      except fibrous-fatty and low-attenuation plaque. Serial CAC measurements may be
      helpful in determining the need for intensification of preventive treatment.

PMID- 29055626
TI  - Pulmonary Arterial Hypertension With Abnormal V/Q Single-Photon Emission Computed
      Tomography.
AB  - OBJECTIVES: This study aimed to evaluate the incidence and clinical outcomes of
      abnormal ventilation/perfusion (V/Q) single-photon emission computed tomography
      (SPECT) without thromboembolism, especially in patients with group I pulmonary
      arterial hypertension (PAH). BACKGROUND: American Heart Association/American
      College of Cardiology and European Society of Cardiology guidelines recommend V/Q
      scan for screening for chronic thromboembolic pulmonary hypertension. The
      significance of patients with abnormal V/Q SPECT findings but no thromboembolism
      demonstrated in further investigations remained unclear. A distinct pattern of
      global patchy changes not typical of thromboembolism is recognized, but
      guidelines for reporting these in the context of PAH are lacking. METHODS: A
      total of 136 patients who underwent V/Q SPECT and right-sided heart
      catheterization showing mean pulmonary arterial pressure >=25 mm Hg were
      included. V/Q SPECT findings were reported using European Association of Nuclear
      Medicine criteria for pulmonary embolism followed by computed tomography
      pulmonary angiography screening for positive thromboembolism and further invasive
      pulmonary angiography for distal thromboembolism. The abnormal V/Q SPECT images
      were further analyzed according to perfusion pattern into focal or global
      perfusion defects. RESULTS: V/Q SPECT showed thromboembolic disease in 44
      patients, but 19 of these patients had no thromboembolism demonstrated by
      pulmonary angiography. Among these patients, 15 of 19 (78.9%) had group I PAH,
      and the majority had diffuse, patchy perfusion defects. After redefining V/Q
      SPECT images according to the perfusion pattern, those patients with global
      perfusion defects had higher mean pulmonary arterial pressure compared with
      patients with focal perfusion defects and normal scans (mean difference +13.9 and
      +6.2 mm Hg, respectively; p = 0.0002), as well as higher pulmonary vascular
      resistance (mean difference +316.6 and +226.3 absolute resistance units,
      respectively; p = 0.004). Among patients with PAH, global perfusion defects were
      associated with higher all-cause mortality with a hazard ratio of 5.63 (95%
      confidence interval: 1.11 to 28.5) compared with patients with focal or no
      perfusion abnormalities. CONCLUSIONS: There is a high incidence of abnormal V/Q
      SPECT scans in nonthromboembolic PAH. Further studies are needed to investigate
      the poor outcome associated with abnormal V/Q SPECT findings in the context of
      PAH.

PMID- 29055627
TI  - Psoriasis-Related Visceral Adiposity and Arterial Inflammation: A New Adiposity
      Disease Entity?

PMID- 29055629
TI  - Early Prosthetic Valve Dysfunction Due to Bioprosthetic Valve Thrombosis: The
      Role of Echocardiography.
AB  - OBJECTIVES: The purpose of this study was to review the institutional practice of
      surveillance transthoracic echocardiography (TTE) for diagnosing early prosthetic
      valve dysfunction (PVD). BACKGROUND: Bioprosthetic valve thrombosis (BPVT) is an
      important cause of PVD, and guidelines do not recommend routine TTE during the
      first 5 years after valve implantation. METHODS: The authors performed a
      retrospective case-control study of all suspected (imaging diagnosis) or
      confirmed (histopathological diagnosis) cases of BPVT from January 1997 through
      December 2016. Patients were matched 1:2 (age, sex, prosthesis position) to
      patients whose prostheses were explanted because of structural failure (SF). PVD
      was defined as a 50% increase above baseline gradient at valve implantation and
      classified as early (<=5 years) or late (>5 years) after implantation. RESULTS:
      There were 94 BPVT (51 suspected, 43 confirmed) and 188 SF cases; patient age 61
      +/- 9 years; men 61 (65%). The prosthesis positions were aortic 56%; mitral 26%;
      tricuspid 15%; and pulmonary 3%. Early PVD was more common in the BPVT versus SF
      group: 83 of 94 (88%) versus 20 of 188 (11%) (p < 0.001). Time from implantation
      to PVD was shorter for BPVT than SF: 26 months (interquartile range [IQR]: 12 to
      43 months) versus 74 months (IQR: 48 to 102 months) (p < 0.001). At the initial
      PVD diagnosis, 81% of BPVT and 90% of SF patients were asymptomatic. However,
      BPVT patients had rapid symptomatic deterioration, requiring intervention sooner
      after PVD diagnosis: 6 months (IQR: 4 to 7 months) versus 51 months (IQR: 22 to
      55 months) (p < 0.001). CONCLUSIONS: Most patients with PVD due to BPVT were
      asymptomatic at initial diagnosis, which was made based on routine surveillance
      TTE, often performed before 5 years. BPVT, an acute disease process, requires
      timely diagnosis because patient conditions rapidly deteriorate. Further studies
      are needed to determine whether routine surveillance TTE should be considered for
      patients with bioprosthetic valves to identify pre-symptomatic features of BPVT
      in order to provide effective, appropriate therapy.

PMID- 29055630
TI  - Cardiac Magnetic Resonance Myocardial Perfusion After Arterial Switch for
      Transposition of Great Arteries.

PMID- 29055631
TI  - Impact of Left Ventricular Trabeculations and Papillary Muscles on Mass,
      Geometry, and Association With Incident Adverse Cardiovascular Events: The
      Framingham Heart Study.

PMID- 29055628
TI  - Visceral Adiposity in Psoriasis is Associated With Vascular Inflammation by 18F
      Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Beyond
      Cardiometabolic Disease Risk Factors in an Observational Cohort Study.
AB  - OBJECTIVES: The authors sought to examine the relationship between visceral
      adipose tissue (VAT) and vascular inflammation (VI) by 18F-Fluorodeoxyglucose
      (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in
      psoriasis (PSO). Furthermore, we evaluated whether treatment of PSO modulated VAT
      and VI. BACKGROUND: PSO, a chronic inflammatory skin disease, is associated with
      VI by 18F-FDG PET/CT and increased cardiometabolic risk including adipose tissue
      dysregulation. Recently, VI was associated with future cardiovascular events;
      however, the relationship of visceral and subcutaneous adiposity with VI in PSO
      has yet to be evaluated. METHODS: Consecutive PSO patients (N = 77) underwent 18F
      FDG PET/CT scans to measure VI and abdominal adiposity. A subset of PSO patients
      with severe skin disease was scanned at 1 year following PSO treatment (N = 13).
      RESULTS: The cohort was middle aged (51.8 +/- 12.6 years), predominantly male (n
      = 44, 57%), had low cardiovascular risk by Framingham 10-year risk (median 4
      years [interquartile range (IQR): 2 to 7 years]), and mild-to-moderate skin
      disease (5.2 [IQR: 3.0 to 8.5]). PSO disease severity associated with VAT (beta =
      0.33; p = 0.004) beyond SAT (beta = 0.30; p = 0.005). VAT (beta = 0.55; p <
      0.001), but not SAT (beta = 0.15; p = 0.11), associated with VI beyond
      cardiovascular risk factors. We followed a subset of severe PSO patients treated
      aggressively for PSO and observed improvement in PSO severity and VAT, which was
      associated with an improvement in VI at 1 year beyond cardiovascular risk factors
      (beta = 0.53; p = 0.049). CONCLUSIONS: Volume-based CT measurement of VAT may
      capture metabolic risk associated with VI compared to subcutaneous adipose tissue
      in PSO. PSO treatment associated with a decrease in VAT as well as decrease in VI
      suggesting VAT as a relevant biomarker related to VI in PSO.

PMID- 29055632
TI  - Intervention Versus Observation in Symptomatic Patients With Normal Flow Low
      Gradient Severe Aortic Stenosis.
AB  - OBJECTIVES: The purpose of this study was to describe patients with severe
      symptomatic aortic stenosis with normal flow and low gradients and determine
      whether they benefit from intervention. BACKGROUND: Severe symptomatic aortic
      stenosis is a progressive disease with high mortality. Although surgical aortic
      valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) are
      indicated for patients with high gradients (>40 mm Hg) or low gradients due to
      low flow, the approach for patients with normal flow and low gradients is poorly
      defined. METHODS: Consecutive adult patients who underwent echocardiography
      between 2012 and 2015 at Tel-Aviv Medical Center and had an aortic valve area of
      <=1.0 cm2, a mean gradient of <40 mm Hg, a stroke volume index of >35 ml/m2, and
      symptoms formed the study group. Patients designated for intervention (SAVR or
      TAVR) had their procedure within 6 months of the echocardiogram; the others were
      treated conservatively. The endpoints were all-cause mortality and cardiac
      related mortality. RESULTS: During the study period, 1,358 patients with an
      aortic valve area of <=1.0 cm2 and symptoms were identified; 34% of these had
      normal flow and low gradient aortic stenosis and 303 were included. After mean
      follow-up of 652 days, 60 patients (20%) had died, with overall mortality rates
      of 28%, 10%, and 12% for conservatively treated, TAVR, and SAVR patients,
      respectively (p < 0.001). Using Cox regression with adjustment for other
      variables, TAVR was associated with improved survival versus conservative
      treatment (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.26 to 0.93; p
      = 0.03), and lower cardiac mortality (HR: 0.30; 95% CI: 0.10 to 0.74; p = 0.007)
      with no significant difference for SAVR versus TAVR. After propensity score
      matching of TAVR and conservatively treated patients, 25 of 94 (28%)
      conservatively treated and 10 of 94 (12%) TAVR patients had died (p = 0.016). In
      the matched cohort, Cox regression showed that TAVR had a significant association
      with improved survival (HR: 0.42; 95% CI: 0.20 to 0.86; p = 0.03). CONCLUSIONS:
      Symptomatic patients with an aortic valve area of <=1.0 cm2, normal flow, and low
      gradient may benefit from intervention as opposed to conservative treatment.

PMID- 29055633
TI  - Colchicine Therapy and Plaque Stabilization in Patients With Acute Coronary
      Syndrome: A CT Coronary Angiography Study.
AB  - OBJECTIVES: The authors sought to evaluate the plaque-modifying effects of low
      dose colchicine therapy plus optimal medical therapy (OMT) in patients post-acute
      coronary syndrome (ACS), as assessed by coronary computed tomography angiography
      (coronary CTA). BACKGROUND: Colchicine therapy has been postulated to have
      beneficial anti-inflammatory effects in patients with ACS, translating into
      reduction in future adverse cardiovascular events. However, whether favorable
      plaque modification underpins this is yet unproven. METHODS: In this prospective
      nonrandomized observational study of 80 patients with recent ACS (<1 month),
      patients received either 0.5 mg/day colchicine plus OMT or OMT alone and were
      followed for 1 year. Our primary outcome was change in low attenuation plaque
      volume (LAPV), a marker of plaque instability on coronary CTA and robust
      predictor of adverse cardiovascular events. Secondary outcomes were changes in
      other coronary CTA measures and in high-sensitivity C-reactive protein (hsCRP).
      RESULTS: Mean duration of follow-up was 12.6 months; mean age was 57.4 years.
      Colchicine therapy significantly reduced LAPV (mean 15.9 mm3 [-40.9%] vs. 6.6 mm3
      [-17.0%]; p = 0.008) and hsCRP (mean 1.10 mg/l [-37.3%] vs. 0.38 mg/l [-14.6%]; p
      < 0.001) versus controls. Reductions in total atheroma volume (mean 42.3 mm3 vs.
      26.4 mm3; p = 0.28) and low-density lipoprotein levels (mean 0.44 mmol/l vs. 0.49
      mmol/l; p = 0.21) were comparable in both groups. With multivariate linear
      regression, colchicine therapy remained significantly associated with greater
      reduction in LAPV (p = 0.039) and hsCRP (p = 0.004). There was also a significant
      linear association (p < 0.001) and strong positive correlation (r = 0.578)
      between change in LAPV and hsCRP. CONCLUSIONS: Our findings suggest, for the
      first time, that low-dose colchicine therapy favorably modifies coronary plaque,
      independent of high-dose statin intensification therapy and substantial low
      density lipoprotein reduction. The improvements in plaque morphology are likely
      driven by the anti-inflammatory properties of colchicine, as demonstrated by
      reductions in hsCRP, rather than changes in lipoproteins. Colchicine may be
      beneficial as an additional secondary prevention agent in patients post-ACS if
      validated in future studies.

PMID- 29055634
TI  - Additional Diagnostic Value of Combined Angio-Computed Tomography and 18F
      Fluorodeoxyglucose Positron Emission Tomography in Infectious Aortitis.

PMID- 29055635
TI  - Effect of Mitral Valve Repair on Mitral Valve Leaflets Strain: A Pilot Study.

PMID- 29055636
TI  - Can a Machine Learn Better Than Humans?

PMID- 29055637
TI  - Impact of Pre-Diabetes on Coronary Plaque Composition and Clinical Outcome in
      Patients With Acute Coronary Syndromes: An Analysis From the PROSPECT Study.
AB  - OBJECTIVES: The aim of this study was to investigate the impact of pre-diabetes
      (pre-DM) on coronary plaque characteristics and ischemic outcomes in patients
      with acute coronary syndromes (ACS). BACKGROUND: Pre-DM (i.e., the early stages
      of glucometabolic disturbance) is common among patients with ACS, but the extent
      to which pre-DM influences coronary plaque characteristics and the risk for
      adverse ischemic events is unclear. METHODS: In the PROSPECT (Providing Regional
      Observations to Study Predictors of Events in Coronary Tree) study, patients with
      ACS underwent quantitative coronary angiography, grayscale intravascular
      ultrasound, and radiofrequency intravascular ultrasound after successful
      percutaneous coronary intervention. Patients were divided into 3 groups according
      to their glucometabolic status, as defined by the American Diabetes Association:
      normal glucose metabolism (NGM), pre-DM, and diabetes mellitus (DM). These groups
      were compared with regard to coronary plaque characteristics and the risk for
      major adverse cardiac events (MACEs) (defined as cardiac death or arrest,
      myocardial infarction, or rehospitalization for unstable or progressive angina).
      RESULTS: Among 547 patients, 162 (29.6%) had NGM, 202 (36.9%) had pre-DM, and 183
      (33.4%) had DM. There were no significant differences between the groups with
      regard to intravascular ultrasound findings indicative of vulnerable plaques.
      Patients with DM had a higher crude rate of MACEs than those with pre-DM or NGM
      (25.9% vs. 16.3% and 16.1%; p = 0.03 and p = 0.02, respectively). In an adjusted
      Cox regression model using NGM as the reference group, DM (hazard ratio: 2.20;
      95% confidence interval: 1.25 to 3.86; p = 0.006) but not pre-DM (hazard ratio:
      1.29; 95% confidence interval: 0.71 to 2.33; p = 0.41) was associated with
      increased risk for MACEs. CONCLUSIONS: Impaired glucose metabolism is common
      among patients presenting with ACS. DM but not pre-DM is associated with an
      increased risk for MACEs. Thus, preventing patients from progressing from pre-DM
      to DM is important. (PROSPECT: An Imaging Study in Patients With Unstable
      Atherosclerotic Lesions; NCT00180466).

PMID- 29055638
TI  - Will Reducing Inflammation Reduce Vascular Event Rates?

PMID- 29055640
TI  - Aortic Stenosis: No Number Trumps Clinical Judgment.

PMID- 29055639
TI  - Prognostic Value of Combined Clinical and Myocardial Perfusion Imaging Data Using
      Machine Learning.
AB  - OBJECTIVES: This study evaluated the added predictive value of combining clinical
      information and myocardial perfusion single-photon emission computed tomography
      (SPECT) imaging (MPI) data using machine learning (ML) to predict major adverse
      cardiac events (MACE). BACKGROUND: Traditionally, prognostication by MPI has
      relied on visual or quantitative analysis of images without objective
      consideration of the clinical data. ML permits a large number of variables to be
      considered in combination and at a level of complexity beyond the human clinical
      reader. METHODS: A total of 2,619 consecutive patients (48% men; 62 +/- 13 years
      of age) who underwent exercise (38%) or pharmacological stress (62%) with high
      speed SPECT MPI were monitored for MACE. Twenty-eight clinical variables, 17
      stress test variables, and 25 imaging variables (including total perfusion
      deficit [TPD]) were recorded. Areas under the receiver-operating characteristic
      curve (AUC) for MACE prediction were compared among: 1) ML with all available
      data (ML-combined); 2) ML with only imaging data (ML-imaging); 3) 5-point scale
      visual diagnosis (physician [MD] diagnosis); and 4) automated quantitative
      imaging analysis (stress TPD and ischemic TPD). ML involved automated variable
      selection by information gain ranking, model building with a boosted ensemble
      algorithm, and 10-fold stratified cross validation. RESULTS: During follow-up
      (3.2 +/- 0.6 years), 239 patients (9.1%) had MACE. MACE prediction was
      significantly higher for ML-combined than ML-imaging (AUC: 0.81 vs. 0.78; p <
      0.01). ML-combined also had higher predictive accuracy compared with MD
      diagnosis, automated stress TPD, and automated ischemic TPD (AUC: 0.81 vs. 0.65
      vs. 0.73 vs. 0.71, respectively; p < 0.01 for all). Risk reclassification for ML
      combined compared with visual MD diagnosis was 26% (p < 0.001). CONCLUSIONS: ML
      combined with both clinical and imaging data variables was found to have high
      predictive accuracy for 3-year risk of MACE and was superior to existing visual
      or automated perfusion assessments. ML could allow integration of clinical and
      imaging data for personalized MACE risk computations in patients undergoing SPECT
      MPI.

PMID- 29055641
TI  - Molecular detection and characterization of zoonotic Anaplasma species in
      domestic dogs in Lusaka, Zambia.
AB  - Although tick-borne pathogens, Anaplasma platys and Anaplasma phagocytophilum are
      recognized as zoonotic agents associated with appreciable morbidity and mortality
      in dogs and humans worldwide, there is limited information on these infections in
      many African countries, including Zambia. The purpose of this study was to
      detect, identify and phylogenetically characterize Anaplasma species from dogs in
      Chilanga District in Lusaka Province, Zambia. A total of 301 blood samples were
      collected from apparently healthy and semi-confined dogs. Initial screening by
      polymerase chain reaction with specific primers targeting the 16S rRNA gene of
      Anaplasma species revealed that 9% (27/301) of our samples were positive.
      Subsequent sequence and phylogenetic analysis of a longer fragment of the 16S
      rRNA and citrate synthase (gltA) genes of four positive samples showed the
      presence of A. platys and an Anaplasma species, which was closely related to
      those detected in dogs in South Africa. This is the first report on molecular
      identification and characterization of canine-associated zoonotic Anaplasma
      species in Zambia.

PMID- 29055642
TI  - Contributions to the knowledge of hard ticks (Acari: Ixodidae) in Colombia.
AB  - The known tick fauna of Colombia includes 58 species (15 Argasidae and 43
      Ixodidae). To add to the knowledge of the biology of ticks in Colombia, hard
      ticks (Ixodidae) were collected from domestic animals or vegetation during 2014
      2016 in 10 of Colombia's Departments. Ticks were identified to species through
      morphological examinations. Taxonomic identification was confirmed for some
      specimens by molecular methods, including phylogenetic analyses inferred from
      three tick genes (cytochrome c oxidase, 16S rDNA, second internal transcribed
      spacer). A total of 1745 tick specimens encompassing 8 species were collected.
      Overall, 5 tick species were recorded on cattle [Amblyomma dissimile, Amblyomma
      mixtum, Dermacentor nitens, Rhipicephalus microplus, Rhipicephalus sanguineus
      sensu lato (s.l.)], 5 on dogs (Amblyomma maculatum, Amblyomma ovale, Amblyomma
      varium, R. microplus, R. sanguineus s.l.), 3 on horses (A. mixtum, D. nitens, R.
      sanguineus s.l.), 3 on donkeys (A. mixtum, D. nitens, R. microplus), 1 on pig (D.
      nitens), and 2 from vegetation (A. mixtum, A. dissimile). This included the first
      records of A. mixtum from two Colombian Departments, indicating that the
      distribution of this tick in Colombia may be broader than currently known.
      Phylogenetic analyses confirmed that R. sanguineus s.l. specimens from 8
      Departments belong to the "tropical species". Moreover, Colombian specimens of A.
      maculatum formed a large clade with GenBank sequences of A. maculatum and A.
      triste, although some Colombian specimens grouped with A. maculatum from the
      United States while others grouped with A. triste from Brazil. Significant
      polymorphisms were observed between specimens of A. ovale or D. nitens; for the
      former species, it is noteworthy that two distinct clades were observed. Our
      study provides new records for 8 tick species parasitizing domestic animals in
      Colombia, including species with veterinary and medical importance in the
      Neotropical region, such as R. microplus, R. sanguineus, D. nitens, A. mixtum,
      and A. maculatum. Noteworthy, we provide the first record of A. varium infesting
      a domestic mammal.

PMID- 29055643
TI  - The geographic distribution of Argas (Persicargas) miniatus and Argas
      (Persicargas) persicus (Acari: Argasidae) in America, with morphological and
      molecular diagnoses from Brazil, Chile and Cuba.
AB  - High similarity of morphological traits has historically overshadowed the
      identities and distributions of poultry-associated soft ticks Argas (Persicargas)
      miniatus and Argas (Persicargas) persicus in America. In order to model the
      occurrence of both parasites in the continent, in the current study we performed
      morphological and molecular analyses to identify ticks collected in hen houses
      from Brazil and northern Chile. Combining these results with literature data, and
      the examination of Argas allotments deposited in the tick collections "Colecao
      Nacional de Carrapatos Danilo Goncalves Saraiva" (Brazil), the "Colecao
      Acarologica do Instituto Butantan Sao Paulo" (Brazil), and the "Coleccion
      Zoologica de la Academia de Ciencia de Cuba" (Cuba), we present a critical list
      with the localities where A. (P.) miniatus and A. (P.) persicus have been
      reported in the American continent. Our results confirmed the presence of A. (P.)
      miniatus in Brazil and Cuba, and A. (P.) persicus in Chile, which in particular,
      constitutes the first molecularly confirmed report of the later species for South
      America. Although A. (P.) miniatus and A. (P.) persicus have been documented in
      21 American countries, the identity of some reports must still be considered as
      uncertain until detailed morphological and/or molecular studies are performed.
      When contrasted to a Koppen-Geiger climate classification, A. (P.) miniatus
      predominantly occurs in equatorial and A. (P.) persicus in arid climates.
      However, until undetermined reports of both species are correctly identified, any
      conclusion on their geo-climatological occurrence throughout the American
      continent would be rather speculative.

PMID- 29055644
TI  - Accuracy of biomarkers obtained from cone beam computed tomography in assessing
      the internal trabecular structure of the mandibular condyle.
AB  - OBJECTIVE: The aim of this study was to validate the ability of cone beam
      computed tomography (CBCT) to measure condylar internal trabecular bone structure
      and bone texture parameters accurately. STUDY DESIGN: Sixteen resected condyles
      of individuals undergoing temporomandibular joint replacement were collected and
      used as samples. These condyles were then radiographically imaged by using
      clinically oriented dental CBCT and research oriented micro-computed tomography
      (micro-CT). The CBCT scans were then compared with the gold standard micro-CT
      scans in terms of 21 bone imaging parameters. Descriptive histologic
      investigation of the specimens was also performed. RESULTS: Significant
      correlations were found for several imaging parameters between the CBCT and micro
      CT images, including trabecular thickness (r = 0.92), trabecular separation (r =
      0.78), bone volume (r = 0.90), bone surface area (r = 0.79), and degree of
      anisotropy measurements (r = 0.77). CONCLUSIONS: Measurements of trabecular
      thickness, trabecular separation, bone volume, bone surface area, and degree of
      anisotropy obtained from high-resolution dental CBCT images may be suitable bone
      imaging biomarkers that can be utilized clinically and in future research.

PMID- 29055645
TI  - Bite force and electromyography evaluation after cranioplasty in patients with
      craniosynostosis.
AB  - OBJECTIVE: This long-term follow-up investigation aimed to assess masticatory
      muscle function in 15 patients with craniosynostosis with detachment of the
      temporal muscle during fronto-orbital advancement 6 years after cranioplasty
      compared with a non-operative stomatognathic healthy cohort in the same age group
      (n = 25). STUDY DESIGN: The follow-up assessment for the operated children
      occurred on average 5.2 +/- 1.7 years after surgery at the age of 7 +/- 1.6
      years. The maximum bite force was assessed, in addition to the bilateral function
      of both temporal and masseter muscles, which were analyzed using superficial
      electromyography. RESULTS: The maximum bite force was 257 +/- 89 N 255 +/- 88 N
      (right/left), respectively, in the group of operated children and 212 +/- 61 N
      and 203 +/- 57 N (right/left), respectively, in the control group, without
      clinical relevant difference between groups. The surface electromyography signal
      of the temporal muscle correlated positively with the bite force and showed a
      slightly lower average resting tone activity in the control group, whereas muscle
      fatigue occurred slightly faster in the operated children in both muscles without
      statistically significant difference between the 2 groups. CONCLUSIONS: There was
      no measurable dysfunction in the temporal muscle after the operative correction
      of craniosynostosis compared with a healthy population of children.

PMID- 29055646
TI  - Adolescent Access to Information on Contraceptives: A Mystery Client Study in
      Mexico.
AB  - PURPOSE: We aimed to evaluate adolescent access to contraceptive information and
      quality of care in a sample of primary care clinics and pharmacies in Mexico and
      their association with health facility and adolescent characteristics. METHODS:
      We selected a random sample of pharmacies (n = 434) and public-sector, primary
      care clinics (n = 327) in Mexico City to be visited by young women posing as
      "mystery clients" looking for contraception or emergency contraception. Access to
      contraception information was measured as the percent of times that women
      received the information they requested. To assess quality of care, we built an
      "adolescent-friendly services" (AFS) score based on the World Health Organization
      framework. Regression models were fitted to evaluate the associations between
      outcomes and health facility and client characteristics. RESULTS: Twenty percent
      of women did not receive the information they requested. Clients seeking
      emergency contraception information had higher odds of obtaining it than clients
      seeking information on contraception (odds ratio 3.08 95% confidence interval
      2.03, 4.67). AFS scores were low, although higher in clinics than in pharmacies
      (5/9 in clinics vs. 3/9 in pharmacies). Younger age and indigenous appearance
      were associated with lower quality as measured by the AFS score. CONCLUSIONS:
      Access to information about contraception in pharmacies and clinics is high, but
      efforts must be made to provide 100% coverage to adolescents. The quality of
      contraception services in pharmacies and clinics is poor and nonequitable,
      favoring older and nonindigenous adolescents. Clinics and pharmacies must strive
      to comply with international AFS guidelines.

PMID- 29055647
TI  - Sextortion of Minors: Characteristics and Dynamics.
AB  - PURPOSE: Sextortion (threats to expose sexual images to coerce victims to provide
      additional pictures, sex, or other favors) has been identified as an emerging
      online threat to youth, but research is scarce. We describe sextortion incidents
      from a large sample of victims (n = 1,385) and examine whether incidents
      occurring to minors (n = 572) are more or less serious than those experienced by
      young adults (n = 813). METHODS: We ran advertising campaigns on Facebook to
      recruit victims of sextortion, ages 18-25, for an online survey. We use cross
      tabulations and logistic regression to analyze incidents that began when 18- and
      19-year-old respondents were minors (ages 17 and younger) and compare them with
      incidents that began at ages 18-25 years. Most minor victims were female (91%)
      and aged 16 or 17 when incidents started (75%). RESULTS: Almost 60% of
      respondents who were minors when sextortion occurred knew perpetrators in person,
      often as romantic partners. Most knowingly provided images to perpetrators (75%),
      but also felt pressured to do so (67%). About one-third were threatened with
      physical assaults and menaced for >6 months. Half did not disclose incidents, and
      few reported to police or websites. Perpetrators against minors (vs. adults) were
      more likely to pressure victims into producing initial sexual images, demand
      additional images, threaten victims for >6 months, and urge victims to harm
      themselves. CONCLUSIONS: Sextortion incidents were serious victimizations, and
      often co-occurred with teen dating violence. We describe resources so that
      practitioners can help victims find support and legal advice and remove posted
      images.

PMID- 29055648
TI  - Prognostic Factors in Patients Undergoing Primary Cytoreductive Surgery for FIGO
      Stage IIIC Ovarian, Tubal or Peritoneal Cancer.
AB  - OBJECTIVE: The aim of the study is to investigate factors related to overall
      survival in advanced stage ovarian, tubal, or peritoneal cancer and to identify
      strong and weak prognostic factors. METHODS: We retrospectively reviewed 190
      patients who underwent primary cytoreductive surgery between 2003 and 2013.
      RESULTS: Median overall survival duration was founded 58 months (95% CI 49-67).
      Five-year overall survival ratio was 48.5%. Presence of tumour at upper abdomen,
      suboptimal cytoreduction (residual >1 cm), surgery without lymphadenectomy, and
      presence of peritoneal ascites more than 1 L had a significantly negative effect
      on overall survival, but not histological grade and CA-125 level, by univariate
      Cox analysis. Age and presence of tumour in the upper abdomen were independent
      poor prognostic factors according to multivariate Cox model (HR 1.025; 95% CI
      1.009-1.040 and HR 1.533; 95% CI 1.039-2.263, respectively). CONCLUSION: This
      study supports that the presence of tumour in the upper abdomen is the most
      important independent poor prognostic factor in patients with performed primary
      surgery for advanced stage ovarian, tubal, and peritoneal cancer. Upper abdominal
      metastasis is the most important predictive factor for optimal cytoreduction (P
      <0.001, HR 6.567; 95% CI 3.059-14.096).

PMID- 29055649
TI  - Socioeconomic inequality in excessive body weight in Indonesia.
AB  - Exploiting the Indonesian Family Life Survey (IFLS), this paper studies the
      transition of socioeconomic-related excess weight disparity, including overweight
      and obesity, from 1993 to 2014. First, we show that the proportions of overweight
      and obese people in Indonesia increased rapidly during the time period covered
      and that poorer groups exhibited a larger annual excess weight growth rate than
      richer groups (7.49 percent vs. 3.01 percent). Second, by calculating the
      concentration index, we confirm that the prevalence of obesity affected
      increasingly poorer segments of Indonesian society. Consequently, the
      concentration index decreased during the study period, from 0.287 to 0.093.
      Finally, decomposing the change in the concentration index of excess weight from
      2000 to 2014, we show that a large part of the change can be explained by a
      decrease in the elasticity of wealth and improved sanitary conditions in poorer
      households. Overall, obesity in Indonesia no longer affects purely the wealthier
      segments of the population but the entire socioeconomic spectrum.

PMID- 29055650
TI  - Big and tall: Does a height premium dwarf an obesity penalty in the labor market?
AB  - Previous studies have shown that both height and weight are associated with
      wages. However, some gaps in our understanding of the relationship between body
      size and wages remain. For example, given a height premium and an obesity
      penalty, due to forces working in opposite directions, the current literature is
      unable to provide clear answers to questions such as whether a tall obese woman
      or a short healthy weight woman would earn a higher wage premium. Using
      Australian data and iso-contour wage curves derived from a semi-parametric wage
      regression model, this paper illustrates the complex nature of the relationship
      between height, weight and wages and how the nature of these differences depends
      on gender and age. As adult height is fixed, a key focus of the paper is
      illustrating for various height ranges whether there are any wage benefits in the
      labor market to increasing or decreasing one's weight. For individuals aged 25-54
      as a whole, I find that there are strong effects of weight reduction at lower
      ends of the height distribution for females (between 1.50-1.70m) but not for
      males (<1.65m). For relatively taller men (>1.85m), a wage premium is found for
      being overweight. For relatively taller women (>1.72m), no penalty for being
      overweight is discernible.

PMID- 29055651
TI  - Miracle near 34th street: Wartime Penicillin Research at St John's University,
      NY.
AB  - In the spring of 1944 Sister Marie Immaculate was awarded a Master of Science
      degree for research on penicillin which she had conducted at St John's University
      in Brooklyn, New York. She gave her motivation for undertaking research in this
      topic as wishing to fulfil her patriotic duty by participating in the quest
      towards making penicillin more readily available to all who needed it. It is
      possible that contemporary media reports suggesting that the power of penicillin
      was comparable to a miracle cure contributed to her interest in the subject at
      the time. In practical terms, her work was to have no bearing in increasing the
      availability of penicillin, but simply by becoming engaged in this endeavour, it
      could be argued that she was enacting the beliefs underlying her religious
      calling. This article explores those beliefs, and proposes an ideological synergy
      between science and religion in respect to Sister Marie Immaculate's faith in
      penicillin's potential to cure the world's ills.

PMID- 29055652
TI  - High serum soluble CD40L levels previously to liver transplantation in patients
      with hepatocellular carcinoma are associated with mortality at one year:
      Methodological issues.

PMID- 29055653
TI  - Predicting Response to Intravesical Bacillus Calmette-Guerin Immunotherapy: Are
      We There Yet? A Systematic Review.
AB  - CONTEXT: Bacillus Calmette-Guerin (BCG) is currently the most effective
      intravesical therapy for nonmuscle invasive bladder cancer, reducing not only
      recurrence rates but also preventing progression and reducing deaths. However,
      response rates to BCG vary widely and are dependent on a multitude of factors.
      OBJECTIVE: To review existing data on clinical, pathologic, immune, and molecular
      markers that allow prediction of BCG response. EVIDENCE ACQUISITION: PubMed and
      MEDLINE search of English language literature was conducted from its inception to
      July 2017 using appropriate search terms. Following systematic literature review
      and analysis of data, consensus voting was used to generate the content of this
      review. EVIDENCE SYNTHESIS: As seen in the EORTC and CUETO risk nomograms,
      clinicopathologic features, especially tumor stage and grade, are the most
      effective predictors of BCG response. Data are less robust with regards to the
      association of response with age, female sex, recurrent tumors, multiplicity of
      tumors, and the presence of carcinoma in situ. Single biomarkers, such as tumor
      p53 and urinary interleukin-2 expression, have had limited success in predicting
      BCG response, possibly due to the multifaceted nature of the generated immune
      response. More comprehensive biomarker panels (eg, urinary cytokines), have a
      more robust correlation with response, as do patterns of urinary cytologic
      fluorescent in-situ hybridization examination. Gene expression data correlate
      with disease progression, but studies examining potential associations with BCG
      response are limited. CONCLUSIONS: Currently, the best predictors of BCG response
      are clinicopathologic features such as tumor grade and stage. Panels of urinary
      cytokines, as well as fluorescent in-situ hybridization patterns of cytologic
      anomalies, appear to be promising biomarkers. The complexity of the immune
      response to BCG and the heterogeneity of bladder cancer suggest that future
      studies should amalgamate measures reflecting innate immune response and
      tumor/stromal gene expression before these can be adopted for clinical use.
      PATIENT SUMMARY: Bacillus Calmette-Guerin (BCG) immunotherapy is an effective
      treatment for many patients with nonmuscle invasive bladder cancer. An
      individual's response to BCG can be predicted by using various features of the
      cancer. In the future, predictive markers using molecular measures of the tumor
      type and the immune response to BCG may allow us to precisely know an
      individual's likely outcome after BCG treatment.

PMID- 29055655
TI  - A peer support intervention in improving glycemic control in patients with type 2
      diabetes.
AB  - OBJECTIVE: This study aims to assess the effectiveness of a peer support
      intervention, in which patients with T2DM were provided ongoing self-management
      support by trained peers with diabetes directed at improving self-care behaviors,
      self-efficacy and life quality. METHODS: In this randomized controlled trial, 200
      patients referred to a diabetes specialty clinic were allocated to peer support
      or control group. Participants in both groups received usual education by
      diabetes educators. Intervention participants worked with the trained volunteer
      peers who encouraged participants to engage in daily self-management and to
      discuss and share their experiences and challenges of diabetes management. The
      primary outcomes were HbA1c, BMI, self-care behaviors, self-efficacy and life
      quality RESULTS: After 6 months, patients in the peer support group experienced a
      significant decline in mean A1c value (P=0.045). Also, mean diabetes self
      management scores, mean self-efficacy scores and mean quality of life scores
      significantly improved in peer support group compared to control group (P values
      <0.001). CONCLUSION: Peer support activities can be successfully applied in
      diabetes self-management, especially in areas with a shortage of professionals
      and economic resources. PRACTICE IMPLICATIONS: Peer support strategies should be
      integrated into our healthcare system to meet minimum needs of people with T2DM
      in Iran.

PMID- 29055656
TI  - Non-evidence based medicine: example of the use of systemic corticosteroids in
      exacerbation of COPD.

PMID- 29055654
TI  - Echocardiographic evaluation of diastolic function in mouse models of heart
      disease.
AB  - BACKGROUND: Mouse models of heart disease are extensively employed. The
      echocardiographic characterization of contractile function is usually focused on
      systolic function with fewer studies assessing diastolic function. Furthermore,
      the applicability of diverse echocardiographic parameters of diastolic function
      that are commonly used in humans has not been extensively evaluated in different
      pathophysiological models in mice. METHODS AND RESULTS: We used high resolution
      echocardiography to evaluate parameters of diastolic function in mouse models of
      chronic pressure overload (aortic constriction), volume overload (aorto-caval
      shunt), heart failure with preserved ejection fraction (HFpEF; DOCA-salt
      hypertension), and acute sarcoplasmic reticulum dysfunction induced by
      thapsigargin - all known to exhibit diastolic dysfunction. Left atrial area
      increased in all three chronic models while mitral E/A was difficult to quantify
      at high heart rates. Isovolumic relaxation time (IVRT) and Doppler E/E' increased
      significantly and the peak longitudinal strain rate during early filling (peak
      reverse longitudinal strain rate) decreased significantly after aortic
      constriction, with the changes being proportional to the magnitude of
      hypertrophy. In the HFpEF model, reverse longitudinal strain rate decreased
      significantly but changes in IVRT and E/E' were non-significant, consistent with
      less severe dysfunction. With volume overload, there was a significant increase
      in reverse longitudinal strain rate and decrease in IVRT, indicating a
      restrictive physiology. Acute thapsigargin treatment caused significant
      prolongation of IVRT and decrease in reverse longitudinal strain rate.
      CONCLUSION: These results indicate that the combined measurement of left atrial
      area plus reverse longitudinal strain rate and/or IVRT provide an excellent
      overall assessment of diastolic function in the diseased mouse heart, allowing
      distinction between different types of pathophysiology.

PMID- 29055657
TI  - Correlation between computed tomography imaging and histopathology in pleomorphic
      adenoma of parotid gland.
AB  - OBJECTIVE: The purpose of this study was to correlate the CT imaging features and
      histopathological findings of pleomorphic adenomas (PA), and also try to identify
      its clinical significance. METHODS: Totally 262 PAs in the parotid gland
      including 18 recurrent cases were retrospectively reviewed with preoperative CT
      and pathologic slides. Each pathologic slide was reviewed by two pathologists to
      calculate mean value of epithelial/mesenchymal component, and the results were
      correlated with features of CT scans. RESULTS: PAs showing high contrast
      enhancement were correlated with high proportion of epithelial components in
      histopathologic findings. PAs with smooth border tend to have high proportion of
      epithelial components. The margin on CT imaging did not consisted with pathologic
      margin of resected specimens. In recurrent PAs, there was a significant
      difference on CT contrast enhancement, not in proportion of epithelial component.
      CONCLUSION: The histopathology and CT imaging features of PAs were variable, but
      we can find the correlation of epithelial component and CT contrast enhancement.
      Further large scale study would be expected to identify the clinical significance
      of CT imaging features and histopathologic findings of PAs.

PMID- 29055658
TI  - Emission probability measurement of gamma- and X- rays in Ra-226 and Pb-210
      decay.
AB  - The emission intensities of 186.21keV, 46.54keV, XL(Bi) and XK(Rn) photons were
      measured with calibrated HPGe detectors. The efficiency was computed with the
      MCNP Monte Carlo code and validated using experimental points. Sources of Ra-226
      were prepared from two different radioactive materials. The X-ray emission
      intensities in Ra-226 decay were determined without X-rays from the daughter
      decay products using a radon emanation source. The standard CMI source with Pb
      210 was used and compared with a source prepared from the NPL solution delivered
      under the EMRP project "Metrology for processing materials with high natural
      radioactivity - MetroNORM".

PMID- 29055659
TI  - Secondary structure and membrane topology of dengue virus NS4A protein in
      micelles.
AB  - Dengue virus (DENV) non-structural (NS) 4A is a membrane protein essential for
      viral replication. The N-terminal region of NS4A contains several helices
      interacting with the cell membrane and the C-terminal region consists of three
      potential transmembrane regions. The secondary structure of the intact NS4A is
      not known as the previous structural studies were carried out on its fragments.
      In this study, we purified the full-length NS4A of DENV serotype 4 into
      dodecylphosphocholine (DPC) micelles. Solution NMR studies reveal that NS4A
      contains six helices in DPC micelles. The N-terminal three helices are
      amphipathic and interact with the membrane. The C-terminal three helices are
      embedded in micelles. Our results suggest that NS4A contains three transmembrane
      helices. Our studies provide for the first time structural information of the
      intact NS4A of DENV and will be useful for further understanding its role in
      viral replication.

PMID- 29055660
TI  - Back hand approach to radial access: The snuff box approach.
AB  - Transradial access is becoming the default strategy for routine coronary
      procedures, but there is still room for improvement. For instance, left radial
      access is known to offer some advantages for graft cases, less tortuosity,
      amongst other potential benefits. The downside has been the applicability of this
      access point on patients with a larger body mass index both from the viewpoint of
      the patient and the operator. The patient must lay with their arm in a supine
      position and the operator as a result must stand in a flexed position for an
      unknown period of time. Additionally, patients with various orthopedic injuries,
      including frozen shoulders, on may be unable to supinate their wrist for optimal
      access. One solution to this dilemma is to approach the radial artery from the
      dorsal aspect of the hand so the wrist can pronate naturally if body habitus
      requires the arm to be shifted towards the operator. This report outlines the
      steps and background behind this approach and an educational opportunity for
      those interested in expanding their access skills.

PMID- 29055661
TI  - Bivalirudin versus heparin, without glycoprotein inhibition, in percutaneous
      coronary intervention: A comparison of ischemic and hemorrhagic outcomes over
      10years.
AB  - OBJECTIVE: The choice of antithrombotic agent used during percutaneous coronary
      intervention (PCI) is controversial. While earlier studies suggested a reduction
      in bleeding events with bivalirudin, these studies were confounded by the
      concomitant use of glycoprotein IIbIIIa inhibitors (GPI) in the heparin group.
      More recent studies have challenged the superiority of bivalirudin, pointing to
      an increased risk of stent thrombosis. Real-world data remains limited. METHODS:
      We queried our institutional catheterization laboratory database for all PCI
      cases performed between January 2003 and December 2012 using only heparin or only
      bivalirudin (no use of GPI). We collected data on relevant patient and procedural
      characteristics and compared both efficacy and safety outcomes. We adjusted for
      baseline differences using coarsened exacting matching. RESULTS: 8061 cases met
      our inclusion criteria. Of these, 34.9% were performed with heparin alone and
      65.1% with bivalirudin. After adjusting for baseline differences, we found that
      those patients receiving heparin had a slightly lower risk of post-procedural
      abrupt vessel closure (0.1% vs 0.5%). All other outcomes favored bivalirudin
      including procedural success (97.2% vs 95.5%), transfusion within 72h (2.2% vs
      4.8%), retroperitoneal bleeding (0.1% vs 0.8%), and all-cause mortality (0.9% vs
      1.9%). Subgroup analysis suggested that outcomes were different only in non
      elective cases and non STEMI cases. CONCLUSION: Heparin appears to offer the
      advantage of slightly reduced risk of abrupt vessel closure post-procedure but at
      the cost of increased hemorrhagic complications and all-cause mortality. This
      difference in outcomes may be limited to non-elective and non STEMI cases with
      femoral access.

PMID- 29055662
TI  - Organization in response to massive afflux of war victims in civilian practice -
      experimental feedback from the November 2015 Paris terrorist attacks.
AB  - The arrival of a large number of war-weapon casualties at a civilian trauma
      center requires anticipation. A plan defining the management principles and the
      respective roles of the involved physicians and nurses and their interaction with
      each other is essential. Uni-directional patient flow associated with adequate
      numbers of staff physicians and nurses under the leadership of a medical director
      is essential to prevent the overwhelming of the trauma center. Routine and
      regular interaction between the pre-hospital medical flow control system and the
      medical director, on one hand, and between surgical teams and the medical
      director, on the other, are necessary to know when to apply "damage control"
      surgical techniques. Based on the feedback of a level 1 trauma center that
      received 53 victims of the November 13, 2015 terrorist attack in Paris, we
      present the factors of success, and the stumbling blocks.

PMID- 29055664
TI  - Long Noncoding RNAs: New Players in Ischaemia-Reperfusion Injury.
AB  - Long noncoding RNAs (lncRNAs) constitute a new class of noncoding RNAs that
      interfere with gene expression. It has been shown that lncRNAs exert
      comprehensive effects on biological processes and are associated with numerous
      diseases such as cancer. However, the possible role of lncRNAs in
      ischaemia/reperfusion (I/R) injury have received relatively little attention.
      Accumulating evidence indicates that lncRNAs are also involved in the progression
      of I/R injury such as myocardial, cerebral, hepatic, renal and mesenteric I/R
      injury. In this review, we summarise the current knowledge of lncRNAs in I/R
      injury, attempting to better explain the molecular mechanism of I/R injury and
      provide new directions for its therapy.

PMID- 29055663
TI  - Damage control: Concept and implementation.
AB  - The concept of damage control (DC) is based on a sequential therapeutic strategy
      that favors physiological restoration over anatomical repair in patients
      presenting acutely with hemorrhagic trauma. Initially described as damage control
      surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic
      trauma, this concept is articulated in three steps: surgical control of lesions
      (hemostasis, sealing of intestinal spillage), physiological restoration, then
      surgery for definitive repair. This concept was quickly adapted for intensive
      care management under the name damage control resuscitation (DCR), which refers
      to the modalities of hospital resuscitation carried out in patients suffering
      from traumatic hemorrhagic shock within the context of DCS. It is based mainly on
      specific hemodynamic resuscitation targets associated with early and aggressive
      hemostasis aimed at prevention or correction of the lethal triad of hypothermia,
      acidosis and coagulation disorders. Concomitant integration of resuscitation and
      surgery from the moment of admission has led to the concept of an integrated DCR
      DCS approach, which enables initiation of hemostatic resuscitation upon arrival
      of the injured person, improving the patient's physiological status during
      surgery without delaying surgery. This concept of DC is constantly evolving; it
      stresses management of the injured person as early as possible, in order to
      initiate hemorrhage control and hemostatic resuscitation as soon as possible,
      evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and
      therapeutic radiological management under the name of radiological DC (DCRad).
      DCS is applied only to the most seriously traumatized patients, or in situations
      of massive influx of injured persons, as its universal application could lead to
      a significant and unnecessary excess-morbidity to injured patients who could and
      should undergo definitive treatment from the outset. DCS, when correctly applied,
      significantly improves the survival rate of war-wounded.

PMID- 29055665
TI  - Transesophageal Speckle Tracking Echocardiography Assessment of Right Ventricular
      Longitudinal Strain: A Tool in Search of Validation.

PMID- 29055666
TI  - Finally Getting the "Attention" It Deserves.

PMID- 29055667
TI  - Comment on: an alternative view on the necessity of EGD prior to sleeve
      gastrectomy.

PMID- 29055668
TI  - Effect of meal size and texture on gastric pouch emptying and glucagon-like
      peptide 1 after gastric bypass surgery.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) accelerates gastric pouch emptying,
      enhances postprandial glucagon-like peptide 1 (GLP-1) and insulin, and lowers
      glucose concentrations. To prevent discomfort and reactive hypoglycemia, it is
      recommended that post-RYGB patients eat small, frequent meals and avoid caloric
      drinks. However, the effect of meal size and texture on GLP-1 and metabolic
      response has not been studied. OBJECTIVES: To demonstrate that frequent minimeals
      and solid meals (S) elicit less GLP-1 and insulin release and less reactive
      hypoglycemia and are better tolerated compared with a single isocaloric liquid
      meal (L). SETTING: A university hospital. METHODS: In this prospective study, 32
      RYGB candidates were enrolled and randomized to L or S groups before gastric
      bypass. Each subject received an L or S 600-kcal single meal (SM) administered at
      hour 0 or three 200-kcal minimeals administered at hours 0, 2, and 4 on 2
      separate days. Twenty-one patients were retested 1 year after RYGB. Blood and
      visual analogue scale measurements were collected up to 6 hours postprandially.
      Outcome measures included gastric pouch emptying, glucose, insulin, and GLP-1;
      hunger, fullness, and stomach discomfort were measured by visual analogue scale.
      RESULTS: Twenty-one were patients retested after RYGB (L: n = 12; S: n = 9). Meal
      texture had a significant effect on peak GLP-1 (L-SM: 106.1 +/- 67.2 versus S-SM:
      45.3 +/- 25.2 pM, P = .004), peak insulin, and postprandial glucose. Hypoglycemia
      was more frequent after the L-SM meal compared with the S-SM. Gastric pouch
      emptying was 2.4 times faster after RYGB but was not affected by texture.
      CONCLUSIONS: Meal texture and size have significant impact on tolerance and
      metabolic response after RYGB.

PMID- 29055669
TI  - Impact of bariatric surgery on outcomes of patients with nonalcoholic fatty liver
      disease: a nationwide inpatient sample analysis, 2004-2012.
AB  - BACKGROUND: Bariatric surgery in eligible morbidly obese individuals may improve
      liver steatosis, inflammation, and fibrosis; however, population-based data on
      the clinical benefits of bariatric surgery in patients with nonalcoholic fatty
      liver disease (NAFLD) are lacking. OBJECTIVES: To assess the relationship between
      bariatric surgery and clinical outcomes in hospitalized patients with NAFLD.
      SETTING: United States inpatient care database. METHODS: The Nationwide Inpatient
      Sample database was queried from 2004 to 2012 with co-diagnoses of NAFLD and
      morbid obesity. Hospitalizations with a history of prior bariatric surgery (Roux
      en-Y gastric bypass, gastric band, and sleeve gastrectomy) were also identified.
      The primary outcome was in-hospital mortality. Secondary outcomes included
      cirrhosis, myocardial infarction, stroke, and renal failure. Poisson regression
      was used to derive adjusted incidence risk ratios for clinical outcomes in
      patients with prior bariatric surgery compared with those without bariatric
      surgery. RESULTS: Among 45,462 patients with a discharge diagnosis of NAFLD and
      morbid obesity, 18,618 patients (41.0%) had prior bariatric surgery. There was a
      downward trend in bariatric surgery procedures (percent annual change of -5.94%
      from 2004 to 2012). In a multivariable analysis, prior bariatric surgery was
      associated with decreased inpatient mortality compared with no bariatric surgery
      (incidence risk ratios = .08; 95% confidence interval, .03-.20, P<.001). Prior
      bariatric surgery was also associated with decreased incidence risk ratios for
      cirrhosis, myocardial infarction, stroke, and renal failure (all P<.001).
      CONCLUSIONS: Prior bariatric surgery is associated with decreased in-hospital
      morbidity and mortality in morbidly obese NAFLD patients. Despite this, the
      proportion of NAFLD patients with bariatric surgery has declined from 2004 to
      2012.

PMID- 29055670
TI  - Conservation and Divergence of p53 Oscillation Dynamics across Species.
AB  - The tumor-suppressing transcription factor p53 is highly conserved at the protein
      level and plays a key role in the DNA damage response. One important aspect of
      p53 regulation is its dynamics in response to DNA damage, which include
      oscillations. Here, we observe that, while the qualitative oscillatory nature of
      p53 dynamics is conserved across cell lines derived from human, monkey, dog,
      mouse, and rat, the oscillation period is variable. Specifically, rodent cells
      exhibit rapid p53 oscillations, whereas dog, monkey, and human cells show slower
      oscillations. Computational modeling and experiments identify stronger negative
      feedback between p53 and MDM2 as the driver of faster oscillations in rodents,
      suggesting that the period of oscillation is a network-level property. In total,
      our study shows that despite highly conserved signaling, the quantitative
      features of p53 oscillations can diverge across evolution. We caution that strong
      amino acid conservation of proteins and transcriptional network similarity do not
      necessarily imply conservation of time dynamics.

PMID- 29055671
TI  - The Interplay between Feedback and Buffering in Cellular Homeostasis.
AB  - Buffering, the use of reservoirs of molecules to maintain concentrations of key
      molecular species, and negative feedback are the primary known mechanisms for
      robust homeostatic regulation. To our knowledge, however, the fundamental
      principles behind their combined effect have not been elucidated. Here, we study
      the interplay between buffering and negative feedback in the context of cellular
      homeostasis. We show that negative feedback counteracts slow-changing
      disturbances, whereas buffering counteracts fast-changing disturbances.
      Furthermore, feedback and buffering have limitations that create trade-offs for
      regulation: instability in the case of feedback and molecular noise in the case
      of buffering. However, because buffering stabilizes feedback and feedback
      attenuates noise from slower-acting buffering, their combined effect on
      homeostasis can be synergistic. These effects can be explained within a
      traditional control theory framework and are consistent with experimental
      observations of both ATP homeostasis and pH regulation in vivo. These principles
      are critical for studying robustness and homeostasis in biology and
      biotechnology.

PMID- 29055672
TI  - Erratum to "pLoc-mVirus: Predict subcellular localization of multi-location virus
      proteins via incorporating the optimal GO information into general PseAAC" [Gene
      628 (2017) 315-321].

PMID- 29055673
TI  - Hemorrhoids during pregnancy: Sitz bath vs. ano-rectal cream: A comparative
      prospective study of two conservative treatment protocols.
AB  - BACKGROUND: Hemorrhoids are a very common ano-rectal condition affecting pregnant
      females worldwide and representing a major medical and socioeconomic problem. In
      this paper, we aim to compare the effectiveness of the Sitz bath method with an
      ano-rectal cream as part of a conservative management protocol to treat
      hemorrhoids among pregnant Saudi Arabian females. METHODS: A prospective
      comparative study of the results of two conservative treatment protocols of 495
      pregnant females diagnosed to have hemorrhoids during pregnancy between January
      2010 and December 2014 was done. The first conservative protocol consisted of
      three times per day salty warm Sitz bath (using 20g of commercial salt) for 284
      patients. The second protocol consisted of topical cream twice daily for 211
      patients. Both protocols included the supportive treatments of 2g glycerin
      suppositories per rectum 20min before defecation as lubricant and Metamucil bulk
      forming fiber (a mix of one dose (sachet) within 240ml (8 oz) of cold liquid)
      once daily after breakfast for constipation. RESULTS: Complete healing was
      achieved in all patients 284 (100%) in the Sitz bath group, compared to 179
      (84.8%) in the cream group. Sitz bath was found to represent a statistically
      significant difference in achieving complete healing for hemorrhoids in pregnant
      Saudi Arabian females compared to an ano-rectal cream (p-value<0.05). CONCLUSION:
      A conservative treatment protocol for hemorrhoids during pregnancy, in which Sitz
      bath is an essential modality, showed very promising outcomes compared to an ano
      rectal cream.

PMID- 29055674
TI  - Combination of a structured aerobic and resistance exercise improves glycaemic
      control in pregnant women diagnosed with gestational diabetes mellitus. A
      randomised controlled trial.
AB  - PROBLEM: Gestational diabetes mellitus, defined as any carbohydrate intolerance
      first diagnosed during pregnancy, is associated with a variety of adverse
      outcomes, both for the mother and her child. AIM: To investigate the impact of a
      structured exercise programme which consisted of aerobic and resistance exercises
      on the parameters of glycaemic control and other health-related outcomes in
      pregnant women diagnosed with gestational diabetes mellitus. METHODS: Thirty
      eight pregnant women diagnosed with gestational diabetes mellitus were randomised
      to two groups. Experimental group was treated with standard antenatal care for
      gestational diabetes mellitus, and regular supervised exercise programme plus
      daily brisk walks of at least 30min. Control group received only standard
      antenatal care for gestational diabetes mellitus. The exercise programme was
      started from the time of diagnosis of diabetes until birth. It was performed two
      times per week and sessions lasted 50-55min. FINDINGS: The experimental group had
      lower postprandial glucose levels at the end of pregnancy (P<0.001). There was no
      significant difference between groups in the level of fasting glucose at the end
      of pregnancy. Also, there were no significant differences in the rate of
      complications during pregnancy and birth, need for pharmacological therapy,
      maternal body mass and body fat percentage gains during pregnancy, and neonatal
      Apgar scores, body mass and ponderal index. Neonatal body mass index was higher
      in the experimental group (P=0.035). CONCLUSION: The structured exercise
      programme had a beneficial effect on postprandial glucose levels at the end of
      pregnancy.

PMID- 29055675
TI  - A transient insulin system dysfunction in newborn rat brain followed by neonatal
      intracerebroventricular administration of streptozotocin could be accompanied by
      a labile cognitive impairment.
AB  - The early postnatal period is a critical period of hippocampus development, which
      is highly dependent on insulin receptor (IR) signaling and very important in
      cognitive function. The present study was conducted in order to present a model
      of neonatal transient brain insulin system dysfunction through finding an
      appropriate dose of injection of streptozotocin (STZ) during the neonatal period.
      Sixty male Wistar rat pups were divided into 4 groups of 15 and received
      intracerebroventricular saline or STZ (icv-STZ) (15, 20 and 25MUg/kg) on
      postnatal day 7. Gene expression of IR and target genes for IR signaling (choline
      acetyltransferase (ChAT) and Tau) were measured at the ages of 2 and 7 weeks.
      Behavioral tests were performed at the ages of 3 and 6 weeks to assess short- and
      long-term cognitive function. 20MUg/kg dose of icv-STZ was estimated as the
      optimal dose causing transient alteration in gene expression of IR, ChAT and Tau.
      Additionally, cognitive function of the animals restored to normal level at the
      age of 6 weeks. Therefore, 20MUg/kg dose of icv-STZ is proposed as a new approach
      to generating transient brain insulin system dysfunction associated with
      transient cognitive impairments at a critical postnatal period of brain
      development.

PMID- 29055676
TI  - CCN1 sensitizes esophageal cancer cells to TRAIL-mediated apoptosis.
AB  - TRAIL is one of the best anti-cancer molecules in our body. It kills a variety of
      cancer cells that are resistant to conventional chemotherapy, without causing
      much negative impact on normal cells, because its death receptors are almost
      exclusively found on cancer cells. However, some cancer cells are not sensitive
      to TRAIL treatment, even though they express its death receptors. A second
      molecule is needed to help TRAIL to complete its mission. Finding such molecules
      now becomes a top priority in cancer research. Our study shows that CCN1 is such
      a molecule. CCN1 was highly expressed in the esophageal epithelium of the
      patients suffering from gastroesophageal reflux disease, but faded away as the
      situation worsened towards adenocarcinoma. Treating the tumor cells with CCN1
      resulted in apoptosis, while the same treatment to the normal cells only
      nourished cell growth. It was TRAIL that mediated this process. Apparently, CCN1
      altered the expression profile of TRAIL and its receptors in tumor cells, namely,
      activating TRAIL and its death receptors and shutting down its decoy receptors.
      CCN1 and TRAIL worked as a team to put the cancer cells to death, as elimination
      of either one failed apoptosis.

PMID- 29055677
TI  - Modeling correlated marker effects in genome-wide prediction via Gaussian
      concentration graph models.
AB  - In genome-wide prediction, independence of marker allele substitution effects is
      typically assumed; however, since early stages in the evolution of this
      technology it has been known that nature points to correlated effects. In
      statistics, graphical models have been identified as a useful and powerful tool
      for covariance estimation in high dimensional problems and it is an area that has
      recently experienced a great expansion. In particular, Gaussian concentration
      graph models (GCGM) have been widely studied. These are models in which the
      distribution of a set of random variables, the marker effects in this case, is
      assumed to be Markov with respect to an undirected graph G. In this paper,
      Bayesian (Bayes G and Bayes G-D) and frequentist (GML-BLUP) methods adapting the
      theory of GCGM to genome-wide prediction were developed. Different approaches to
      define the graph G based on domain-specific knowledge were proposed, and two
      propositions and a corollary establishing conditions to find decomposable graphs
      were proven. These methods were implemented in small simulated and real datasets.
      In our simulations, scenarios where correlations among allelic substitution
      effects were expected to arise due to various causes were considered, and graphs
      were defined on the basis of physical marker positions. Results showed
      improvements in correlation between phenotypes and predicted additive genetic
      values and accuracies of predicted additive genetic values when accounting for
      partially correlated allele substitution effects. Extensions to the multiallelic
      loci case were described and some possible refinements incorporating more
      flexible priors in the Bayesian setting were discussed. Our models are promising
      because they allow incorporation of biological information in the prediction
      process, and because they are more flexible and general than other models
      accounting for correlated marker effects that have been proposed previously.

PMID- 29055678
TI  - Modeling the spread of capripoxvirus among livestock and optimal vaccination
      strategies.
AB  - Capripox is an important transboundary animal disease that is endemic across
      Africa, the Middle East, and some parts of Asia. The disease is highly contagious
      and considered to be a major obstacle causing significant economic loses in many
      agricultural areas. In this study, a mathematical model is developed to describe
      the transmission dynamics of capripoxvirus (CaPV) among livestock. This proposed
      model incorporates direct and indirect transmission of CaPV, together with two
      vaccination strategies, to investigate their effects on the severity of outbreaks
      and the prevalence of CaPV among the livestock population. The results suggest
      that ratio of potential vectors to livestock, successful probability of
      infection, vaccination rates, waning rate of vaccine-conferred protection, and
      virus introduction time play crucial roles in determining the outbreak severity
      and the prevalence level. The results also show that it is optimal to vaccinate
      newborns at the maximum effort throughout the control program and moderately
      increase vaccination rate for a susceptible pool to reach its maximum level after
      the outbreak.

PMID- 29055679
TI  - Cerebral metabolic correlates of attention networks in Alzheimer's Disease: A
      study of the Stroop.
AB  - Patients with Alzheimer's Disease (AD) show difficulties with attention.
      Cognitive neuroscience models posit that attention can be broken down into
      alerting, orienting, and executive networks. We used the Stroop Color-Word test
      to interrogate the neural correlates of attention deficits in AD. We hypothesized
      that the Word, Color, and Color-Word conditions of the Stroop would all tap into
      the alerting and orienting networks. The Color-Word condition would additionally
      tap into the executive network. A ratio of Color-Word to Color naming performance
      would isolate the executive network from the others. To identify the neural
      underpinnings of attention in AD we correlated performance on the Stroop with
      brain metabolic activity. Sixty-six patients with probable AD completed [18F]
      fluorodeoxyglucose PET scanning and neuropsychological testing. Analysis was
      conducted with SPM12 (p<0.001 uncorrected, extent threshold 50 voxels).
      Performance on the Word, Color, and Color-Word conditions directly correlated
      with metabolic rate in right inferior parietal lobules/intraparietal sulci. The
      Color-Word/Color ratio revealed associations with metabolic rate in right medial
      prefrontal cortex and insula/operculum. Overall findings were largely consistent
      with the hypothesized neuroanatomical substrates of the alerting, orienting, and
      executive networks. As such, attention deficits in AD reflect compromise to
      multiple large-scale networks.

PMID- 29055681
TI  - The Effects of Exposure to Environmental Cigarette Smoke on the Vocal Folds of
      Rats.
AB  - OBJECTIVE: This study aimed to investigate histopathologically and
      immunohistochemically the effects of environmental smoke on the vocal folds.
      METHODS: This study examined 20 healthy Wistar albino rats, which were divided
      into four groups of five rats. Group 1 was exposed to smoke for 45 days and group
      2 for 90 days. Groups 3 and 4 were the respective control groups. The rats in
      groups 1 and 3 were sacrificed on day 45 and those in groups 2 and 4 on day 90.
      The larynx specimens were stained with hematoxylin and eosin, and the
      inflammation, hyperplasia, and metaplasia were evaluated. Ki-67 staining was used
      for the immunohistochemical analysis. RESULTS: There was no significant
      difference in mononuclear cell infiltration between the experimental and control
      groups (group 1 vs. group 3 P = 0.20, group 2 and 4 P = 0.41) (Table 3), but
      there was a significant difference between the two experimental groups (P =
      0.007). Mild and moderate hyperplasia was seen in groups 1 and 2, respectively.
      CONCLUSION: Environmental exposure to cigarette smoke has destructive effects on
      the vocal folds of rats.

PMID- 29055680
TI  - Oxytocin increases attention to the eyes and selectively enhances self-reported
      affective empathy for fear.
AB  - Oxytocin (OXT) has previously been implicated in a range of prosocial behaviors
      such as trust and emotion recognition. Nevertheless, recent studies have
      questioned the evidence for this link. In addition, there has been relatively
      little conclusive research on the effect of OXT on empathic ability and such
      studies as there are have not examined the mechanisms through which OXT might
      affect empathy, or whether OXT selectively facilitates empathy for specific
      emotions. In the current study, we used eye-tracking to assess attention to
      socially relevant information while participants viewed dynamic, empathy-inducing
      video clips, in which protagonists expressed sadness, happiness, pain or fear. In
      a double-blind, within-subjects, randomized control trial, 40 healthy male
      participants received 24 IU intranasal OXT or placebo in two identical
      experimental sessions, separated by a 2-week interval. OXT led to an increase in
      time spent fixating upon the eye-region of the protagonist's face across
      emotions. OXT also selectively enhanced self-reported affective empathy for fear,
      but did not affect cognitive or affective empathy for other emotions.
      Nevertheless, there was no positive relationship between eye-gaze patterns and
      affective empathy, suggesting that although OXT influences eye-gaze and may
      enhance affective empathy for fear, these two systems are independent. Future
      studies need to further examine the effect of OXT on eye-gaze to fully ascertain
      whether this can explain the improvements in emotional behavior.

PMID- 29055682
TI  - Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose
      Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post
      Transplant Cyclophosphamide.
AB  - Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms,
      post-transplantation cyclophosphamide (PTCy) after T cell-replete HLA
      haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of
      grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of
      grade II aGVHD. Given that mild GVHD has been associated with reduced treatment
      failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD
      on survival in 340 adults with hematologic malignancies who engrafted after
      nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The
      cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30%
      (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%),
      respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to
      13%). In landmark analyses at 100 days, the 4-year probabilities of overall
      survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%)
      and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared
      with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with
      grade II aGVHD (P = .05 and P = .009). In multivariable modeling, when compared
      with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in
      patients with grade II aGVHD was .78 (95% CI, .54 to 1.13; P = .19) and .69 (95%
      CI, .48 to .98; P = .04). Higher nucleated cell graft dose was also associated
      with improved OS (HR, .88; 95% CI, .78 to 1.00; P = .05) and PFS (HR, .89; 95%
      CI, .79 to 1.0; P = .05) and decreased risk of grades III to IV aGVHD
      (subdistribution HR, .66; 95% CI, .46 to .96; P = .03). PTCy reduces grades III
      to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the
      development of which improves PFS. Higher nucleated cell graft dose goals may
      also improve survival after nonmyeloablative haplo-BMT with PTCy.

PMID- 29055683
TI  - Spectral Beam Shaping in Unenhanced Chest CT Examinations: A Phantom Study on
      Dose Reduction and Image Quality.
AB  - RATIONALE AND OBJECTIVES: This study aimed to determine the optimal tube
      potential for unenhanced chest computed tomographies (CTs) with age-related
      phantoms. MATERIALS AND METHODS: Three physical anthropomorphic phantoms
      (newborn, 5-year-old child, and adult) were scanned on a third-generation dual
      source CT using CAREkV in semi-mode and CAREDose4D (ref. KV: 120; ref. mAs 50).
      Scans were performed with all available tube potentials (70-150 kV and Sn150 kV).
      The lowest volume computed tomography dose index (CTDIvol) was selected to
      perform additional Sn100-kV scans with matched and half (Sn100-half) CTDIvol
      value. Image quality was evaluated on the basis of contrast-to-noise ratio (CNR).
      RESULTS: For the newborn phantom, 70-110 kV was selected as the optimal range
      (0.36-0.37 mGy). Using Sn150 kV led to an increase in radiation dose (0.75 mGy)
      without improving CNR (96.9 vs 101.5). Sn100-half showed a decrease in CNR (73.1
      vs 101.5). The lowest CTDIvol for the child phantom was achieved between 100 and
      120 kV (0.78-0.80 mGy). Using Sn150 kV increased radiation dose (1.02 mGy)
      without improvement of CNR (92.4 vs 95.8). At Sn100-half CNR was decreased (61.4
      vs 95.8). For adults, 140 and 150 kV revealed the lowest CTDIvol (2.68 and 2.67
      mGy). The Sn150 kV scan delivered comparable CNR (54.4 vs 56.6), but a lower
      CTDIvol (2.08 mGy). At Sn100-half CNR was comparable to the 150 kV scan (58.1 vs
      56.6). CONCLUSION: Unenhanced chest CT performed at 100 kV or 150 kV with tin
      filtration enables radiation dose reduction for the adult phantom, but not for
      the pediatric phantoms.

PMID- 29055684
TI  - [COPD: the great unknown? A note on how to improve diagnostic accuracy].

PMID- 29055685
TI  - Moments of disaster response in the emergency department (ED).
AB  - BACKGROUND: We experience our lives as a series of memorable moments, some good
      and some bad. Undoubtedly, the experience of participating in disaster response,
      is likely to stand out as a memorable moment in a nurses' career. This
      presentation will describe five distinct moments of nursing in the emergency
      department (ED) during a disaster response. METHODS: A Hermeneutic
      Phenomenological approach informed by van Manen underpins the research process.
      Thirteen nurses from different countries around the world participated in
      interviews about their experience of working in the ED during a disaster.
      Thematic analysis resulted in five moments of disaster response which are common
      to the collective participant experience. RESULTS: The 5 themes emerge as
      Notification (as a nurse finds out that the ED will be receiving casualties),
      Waiting (waiting for the patients to arrive to the ED), Patient Arrival (the
      arrival of the first patients to the ED), Caring for patients (caring for people
      affected by the disaster) and Reflection (the moment the disaster response comes
      to an end). CONCLUSION: This paper provides an in-depth insight into the
      experience of nursing in the ED during a disaster response which can help
      generate awareness and inform future disaster preparedness of emergency nurses.

PMID- 29055686
TI  - The role of explorative tympanotomy in patients with sudden sensorineural hearing
      loss with and without perilymphatic fistula.
AB  - PURPOSE: The purpose of this study was to describe the role of explorative
      tympanotomy in patients with Profound Sudden Sensorineural Hearing Loss (SSNHL)
      without clinical evidence of perilymphatic or labyrinthine fistula and to compare
      intraoperative findings with the postoperative hearing outcome. STUDY DESIGN:
      Retrospective study of all patients diagnosed with SSNHL who underwent
      explorative tympanotomy between 2002 and 2005. SETTINGS: Tertiary care university
      affiliated hospital. SUBJECTS AND METHODS: Eighty-two patients were diagnosed
      with unilateral profound SSNHL and underwent tympanotomy with sealing of the
      round and oval windows. Values of pure tone audiograms and percentage hearing
      loss of patients with and without intraoperative diagnosed perilymphatic fistula
      (PLF) were compared and analyzed. RESULTS: PLF was diagnosed in 28% cases
      intraoperatively. In most cases, hearing improved significantly after surgery.
      Interestingly, patients with PLF had a 2.4 times greater decrease of percentage
      hearing loss compared to patients without PLF. CONCLUSIONS: Explorative
      tympanotomy seems to be useful in patients with profound SSNHL. Patients with PLF
      benefit more from the surgical procedure and have better outcome than patients
      without PLF.

PMID- 29055687
TI  - Sphingosine kinase 1 in breast cancer.
AB  - Breast cancer affects 1 out of 8 women in the US and is the second highest cause
      of death from cancer for women, leading to considerable research examining the
      causes, progression, and treatment of breast cancer. Over the last two decades,
      sphingosine-1-phosphate (S1P), a potent sphingolipid metabolite, has been
      implicated in many processes important for breast cancer including growth,
      progression, transformation and metastasis, and is the focus of this review. In
      particular, one of the kinases that produces S1P, sphingosine kinase 1 (SphK1),
      has come under increasing scrutiny as it is commonly upregulated in breast cancer
      cells and has been linked with poorer prognosis and progression, possibly leading
      to resistance to certain anti-cancer therapies. In this review, we will also
      discuss preclinical studies of both estrogen receptor (ER) positive as well as
      triple-negative breast cancer mouse models with inhibitors of SphK1 and other
      compounds that target the S1P axis and have shown good promise in reducing tumor
      growth and metastasis. It is hoped that in the future this will lead to
      development of novel combination approaches for effective treatment of both
      conventional hormonal therapy-resistant breast cancer and triple-negative breast
      cancer.

PMID- 29055688
TI  - Ciprofloxacin treatment for cryptogenic Klebsiella pneumoniae liver abscesses.

PMID- 29055689
TI  - Targeting neutrophils for host-directed therapy to treat tuberculosis.
AB  - M. tuberculosis is one of the prime killers from infectious diseases worldwide.
      Infections with multidrug-resistant variants counting for almost half a million
      new cases per year are steadily on the rise. Tuberculosis caused by extensively
      drug-resistant variants that are even resistant against newly developed or last
      resort antibiotics have to be considered untreaTable Susceptible tuberculosis
      already requires a six-months combinational therapy which requires further
      prolongation to treat drug-resistant infections. Such long treatment schedules
      are often accompanied by serious adverse effects causing patients to stop
      therapy. To tackle the global tuberculosis emergency, novel approaches for
      treatment need to be urgently explored. Host-directed therapies that target
      components of the defense system represent such a novel approach. In this review,
      we put a spotlight on neutrophils and neutrophil-associated effectors as
      promising targets for adjunct host-directed therapies to improve antibiotic
      efficacy and reduce both, treatment time and long-term pathological sequelae.

PMID- 29055690
TI  - Application of digital PCR with chip-in-a-tube format to analyze Adenomatous
      polyposis coli (APC) somatic mosaicism.
AB  - BACKGROUND: Over the past decade, digital PCR (dPCR) technology has significantly
      improved, and its application in clinical diagnostics is rapidly advancing. The
      ClarityTM dPCR platform, which employs the chip-in-a-tube format to broaden its
      range of applications, has been used to determine gene copy number. However,
      detection of mutations in human samples, the most demanding task in clinical
      practice, has not yet been reported using this platform. METHODS: The ClarityTM
      dPCR platform was used to detect somatic Adenomatous polyposis coli mosaicism
      c.834+2T>C, which had been identified using next-generation sequencing (NGS)
      technology in a patient with sporadic familial adenomatous polyposis. In
      addition, we were able to determine the size of the dPCR product. RESULTS: The
      mutation rate in the peripheral blood of the patient calculated using the dPCR
      platform was 13.2%. This was similar to that determined using NGS (12.7%). In
      contrast, in healthy donors, the mutation rate was <0.1%. Furthermore, it was
      confirmed that the dPCR product size was consistent with its theoretical value.
      CONCLUSION: Our results show that the dPCR platform with the chip-in-a-tube
      format is suitable for the analysis of mosaicism and enables the validation of
      the dPCR product size.

PMID- 29055691
TI  - Urinary and circulating levels of the anti-angiogenic isoform of vascular
      endothelial growth factor-A in patients with chronic kidney disease.
AB  - INTRODUCTION: The protective effects of vascular endothelial growth factor (VEGF)
      A165b on kidney tissue have been suggested in animal studies. However, the
      relevance of urinary and circulating VEGF-A165b levels in chronic kidney disease
      patients remains unclear. Therefore, the present study aimed to investigate the
      urinary and circulating VEGF-A165b levels in patients with chronic kidney
      disease. METHODS: This observational study enrolled a total of 92 Japanese
      patients with chronic kidney disease, who had undergone inulin renal clearance
      measurements for the accurate assessment of measured GFR. Urinary or circulating
      total VEGF-A and VEGF-A165b levels were measured using enzyme-linked
      immunosorbent assay. RESULTS: Urinary VEGF-A165b levels were significantly lower
      in G3a, G3b, and G4+G5 category patients than in G1+G2 category patients.
      Correlation analysis found that serum creatinine levels, serum cystatin C levels,
      eGFRcre, eGFRcys, and mGFR were weakly but significantly correlated with urinary
      VEGF-A165b levels. Additionally, circulating VEGF-A165b levels were significantly
      higher in G4+G5 category patients than in G1+G2 category patients. CONCLUSION: A
      low urinary VEGF-A165b level reflects renal dysfunction in the chronic kidney
      disease stage, while a high circulating VEGF-A165b level cannot be attributed to
      decreased renal clearance.

PMID- 29055692
TI  - The use of FDI criteria in clinical trials on direct dental restorations: A
      scoping review.
AB  - OBJECTIVES: A scoping review was conducted to explore the use of FDI criteria 10
      years after their introduction. The first aim was to compare the amount of
      studies using the FDI and/or the modified USPHS criteria. The second aim was to
      analyse the use of the FDI criteria in clinical trials evaluating direct dental
      restorations. DATA: Listing of studies using FDI and/or USPHS criteria per year
      since 2007. Clinical studies related to the assessment of direct restorations
      using FDI criteria. SOURCE: Two systematic searches - regarding the use of FDI
      and modified USPHS criteria - were carried out on Medline/Pubmed in order to
      identify the studies published between 2007 and 2017. Authors of the included
      articles were contacted to clarify their choice of FDI criteria in their studies.
      ClinicalTrials.gov database was also queried for the on-going studies that use
      FDI and modified USPHS criteria. STUDY SELECTION: In the first review, all the
      clinical trials (randomized/non-randomized, controlled, prospective/retrospective
      studies) that used FDI criteria to evaluate direct restorations on primary or
      permanent teeth were included. CONCLUSIONS: 16.3% of the studies used FDI
      criteria. The percentage of studies using them increased from 4.5% in 2010 to
      50.0% in 2016. In average, 8.5 FDI criteria were used. The most employed criteria
      were: marginal adaptation (96.7%), staining (90.0%), fracture of material and
      retention (90.0%), recurrence of caries/erosion/abfraction (90.0%), post
      operative sensitivity/tooth vitality (86.7%) and surface luster (60.0%). In
      addition, among the 27 on-going studies from ClinicalTrials.gov database, 51.9%
      use FDI criteria (including 87.5% with an open recruitment status). CLINICAL
      SIGNIFICANCE: FDI criteria were reported as practical (various and freely
      selectable), relevant (sensitive as well as appropriate to current restorative
      materials and clinical studies design), standardized (making comparisons between
      investigations easier). Investigators should go on using them for a better
      standardization of their clinical judgment, allowing comparisons with other
      studies.

PMID- 29055693
TI  - Identification and characterization of phosphate transporter genes in potato.
AB  - Phosphate transporter (PHTs) have important roles in Pi acquisition, allocation,
      and signal transduction. The aim of this study is to provide a comprehensive
      knowledge of PHTs in potato. Very strict homology search and subsequent domain
      verification using Hidden Markov Models revealed that the potato genome has 20
      StPHT and StPHOs genes which were grouped into 5 phylogenetical clusters
      including 8 PHT1 homologs,1 PHT2 homolog, 2 PHT3 homologs, 5 PHT4 homologs and 4
      PHO homologs. These genes were mapped on ten S. tuberosum chromosomes (chr1-9 and
      12). Analysis of these genes led to identification of 20 conserved motifs and
      location prediction showed that PHT1 and PHT4 proteins have 12 transmembrane (TM)
      domains, PHT2 proteins have 13 TM domains, PHT3 proteins contain 4-5 TM domains,
      and PHO proteins contain 8-10 TM domains. Two tandem and 2 segmental duplications
      were further identified from these genes. RT-qPCR analysis showed that most of
      PHTs and PHOs displayed specific expression patterns with respect to phosphate
      status, fourteen transporters were up regulated in leaves and 11 transporters
      were up regulated in roots under phosphate deprivation. StPHT2;1 was found to be
      expressed both in potato leaf and root after phosphate starvation. Most cis
      regulatory elements in StPHTs and StPHOs were found associated with light,
      defense, stress and hormones responsiveness, endosperm and meristem expression,
      as well as circadian control. A scan of the coding sequences of 20 StPHTs and
      StPHOs against published miRNAs in potato predicted a total of 2 potential
      miRNAs, mainly targeting members located on the same chromosome. Expression of
      StPHTs and StPHOs was selectively induced by biotic and abiotic stresses, and
      phytohormone treatments, among them, heat stress exclusively caused the up
      regulation of 14 StPHT and StPHO genes, in particular PHO1 members. Most of
      StPHTs and StPHOs do not exhibit the tissue-specific expression. StPHT1;7,
      StPHT3;1 and StPHTO1;1 were highly expressed in the root of S. tuberosum,
      especially the gene StPHT3;1 are highly expressed in 14 tissues which covering
      the entire life cycle of potato. Our results provide comprehensive insights into
      the PHT and PHO family genes involved in the growth, development, and stress
      response of the potato.

PMID- 29055694
TI  - DNA barcoding of metacestodes found in the Guerlinguetus ingrami (Rodentia:
      Sciuridae) reveals the occurrence of Hydatigera taeniaeformis sensu stricto
      (Cyclophyllidea: Taeniidae) in the Americas.
AB  - The existence of cryptic species in the genus Hydatigera, cyclophillid cestodes,
      mainly of felids, was recently described based on molecular studies of parasites
      from Asia, Europe and Africa. However, the occurrence of H. taeniaeformis sensu
      stricto (s.s.), the species more widely distributed and with a presumed
      specificity for murid rodents as intermediate hosts, has not been formally
      described in Americas. In the present study, during necropsy of an Ingram's
      squirrel specimen, Guerlinguetus ingrami, found dead in the municipality of Belo
      Horizonte, Minas Gerais state, Brazil, strobilocerci were found in the liver. The
      metacestodes were subjected to morphological and molecular studies. Sequences of
      the COI barcode region were obtained and used for phylogenetic analyses. The
      morphology and measures of the rostellar hooks were compatible with the ones
      described for H. taeniaeformis s.s. This identification was confirmed by a
      molecular phylogenetic approach (96.2-99.7% similarity with isolates of the
      parasite from Europe and Asia). This is the first molecular confirmation of the
      existence of H. taeniaeformis s.s. on the American continent. Moreover, the
      involvement of sciurid rodents in the transmission of H. taeniaeformis s.s. is
      discussed here as a probable case of parasite spillover.

PMID- 29055696
TI  - New methods to optimally detect episodes of non-metabolic heart rate variability
      reduction as an indicator of psychological stress in everyday life.
AB  - Cardiovascular disease is the leading cause of death in the western world.
      Frequent or chronic reductions in heart rate variability (HRV) are a powerful
      predictor of cardiovascular disease. Psychological stress has been suggested to
      be an important factor in the development of reduced HRV. Recently, Verkuil et
      al. (2016) introduced a laboratory-based method to measure additional HRV
      reduction in everyday life, and reductions in HRV related to psychological
      stress. In the current paper, we discuss alternative methods to detect additional
      HRV reductions, in real life data sets without the necessity of laboratory-based
      calibration, and even in existing data sets. All of these methods use a subset of
      24h' worth of HRV and movement data to do so: either the first 10min of every
      hour, the full 24h, a combination of 10min from three consecutive hours, or a
      classification of level of movement. We also present a method to visualize HRV
      and movement data to be able to detect episodes of reduced additional HRV
      optically. The method that used the full 24h' worth of data detected the largest
      percentage of episodes of reduced additional HRV that actually match with self
      reported stress levels, making this method the most promising.

PMID- 29055695
TI  - Conserved expression of ultra-conserved noncoding RNA in mammalian nervous
      system.
AB  - T-UCRs, a class of long non-coding RNAs that are transcribed from ultra-conserved
      regions (UCRs), might play an important role in development and diseases.
      However, the amount of T-UCRs that are conservatively expressed in the developing
      nervous systems of mice, monkeys and humans is still unknown. In this study, we
      screened the RNA sequence signals of 481 identified UCRs in an E14.5 mouse brain
      from the ENCODE database and found 76 UCRs that may be transcribed into T-UCRs.
      To verify the expression of these potential T-UCRs, we used an RT-PCR experiment
      and identified that 60 T-UCRs can be expressed in the E14.5 mouse brain.
      Furthermore, we detected the expression conservation of 76 potential T-UCRs in
      two comparisons: postnatal day 0 brains of a mouse and a rhesus monkey and neural
      stem cells of mouse and human by RT-PCR experimentation. It was found that up to
      65% of these T-UCRs were expressed in mouse, rhesus monkey and human nervous
      systems. Next, by testing the spatiotemporal expression pattern of these T-UCRs
      expressed in mouse, rhesus monkey and human nervous systems, we found that
      approximately 30% of the T-UCRs showed a relatively high and dynamical expression
      during mouse brain development. Finally, through biological process and molecular
      function gene ontology analysis of the host genes of intronic or exonic-antisense
      T-UCRs, it was discovered that most of the genes were involved in RNA splicing or
      RNA binding. These results suggest that T-UCRs are likely to participate in
      nervous system development through RNA processing.

PMID- 29055698
TI  - Formation of new, cytocompatible hydrogels based on photochemically crosslinkable
      levan methacrylates.
AB  - Levan is a high molecular weight fructose-based biotechnologically available
      polysaccharide with a range of interesting properties qualifying this molecule
      for applications in biomedicine. In this study, new levan derivatives containing
      methacrylate groups attached either via ester or urethane linkages to the fructan
      backbone could be synthesized and structurally characterized by conventional
      analytical techniques. The photochemical crosslinking of these substances
      applying different photoinitiator systems and reaction conditions resulted in
      hydrogels of diverse properties which were investigated with regard to mechanical
      behaviour, hydrolytic degradability, and cytocompatibility. It was found that
      crosslinkable levan derivatives represent a new class of promising biopolymer
      based macromers broadening the spectrum of available biomaterials to facilitate
      the adaption to the requirements of specific applications.

PMID- 29055697
TI  - Cocaine alters Homer1 natural antisense transcript in the nucleus accumbens.
AB  - Natural antisense transcripts (NATs) are an abundant class of long noncoding RNAs
      that have recently been shown to be key regulators of chromatin dynamics and gene
      expression in nervous system development and neurological disorders. However, it
      is currently unclear if NAT-based mechanisms also play a role in drug-induced
      neuroadaptations. Aberrant regulation of gene expression is one critical factor
      underlying the long-lasting behavioral abnormalities that characterize substance
      use disorder, and it is possible that some drug-induced transcriptional responses
      are mediated, in part, by perturbations in NAT activity. To test this hypothesis,
      we used an automated algorithm that mines the NCBI AceView transcriptomics
      database to identify NAT overlapping genes linked to addiction. We found that 22%
      of the genes examined contain NATs and that expression of Homer1 natural
      antisense transcript (Homer1-AS) was altered in the nucleus accumbens (NAc) of
      mice 2h and 10days following repeated cocaine administration. In in vitro
      studies, depletion of Homer1-AS lead to an increase in the corresponding sense
      gene expression, indicating a potential regulatory mechanisms of Homer1
      expression by its corresponding antisense transcript. Future in vivo studies are
      needed to definitely determine a role for Homer1-AS in cocaine-induced behavioral
      and molecular adaptations.

PMID- 29055699
TI  - Natural and synthetic polymer for graphene oxide mediated anticancer drug
      delivery-A comparative study.
AB  - Two dimensional graphene and its derivatives have been a focus of scientific
      study due to its unique features which makes it suitable for biomedical
      applications. Herein a comparative study was carried out between chitosan
      polymerized graphene oxide and polyvinylpyrrolidone polymerized graphene oxide
      nanoparticles. The polymerized nanocarriers were further decorated with folic
      acid and anticancer drug camptothecin was loaded. The nanocarriers thus
      synthesized were characterized by x-ray diffractometer (XRD), fourier transform
      infrared spectroscopy (FTIR), scanning electron microscope (SEM), transmission
      electron microscope (TEM), atomic force microscopy (AFM), thermogravimetric
      analysis (TGA), UV-vis spectroscopy (UV), zeta potential and fluorescence
      spectroscopy. The biocompatibility of the two nanocarriers was compared via
      hemolysis and anti-inflammatory studies and the cellular toxicity was assayed by
      3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and
      Sulforhodamine B (SRB) assay against MCF-7 cell lines. The study indicates that
      chitosan polymerized graphene oxide nanocarrier was more suitable for biomedical
      applications in comparison to polyvinylpyrrolidone. The percentage hemolysis
      caused by chitosan polymerized graphene oxide was almost equivalent to diclofenac
      salt which served as standard. Also it has, increased drug loading capacity and
      greater percentage inhibition of MCF-7 cell lines as per MTT and SRB assay.

PMID- 29055700
TI  - Anti-Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple
      negative breast cancer therapy.
AB  - Trop2, a transmembrane glycoprotein, has emerged as a biomarker for targeted
      cancer therapy since it is overexpressed in 80% of triple negative breast cancer
      (TNBC) patients. For the site-specific delivery of the anticancer drug into TNBC,
      anti-Trop2 antibody-conjugated nanoparticles (ST-NPs) were prepared as the
      potential nanocarrier, composed of carboxymethyl dextran (CMD) derivatives with
      bioreducible disulfide bonds. Owing to its amphiphilicity, the CMD derivatives
      were self-assembled into nano-sized particles in an aqueous condition.
      Doxorubicin (DOX), chosen as a model anticancer drug, was effectively
      encapsulated into the nanoparticles. DOX-loaded ST-NPs (DOX-ST-NPs) rapidly
      released DOX in the presence of 10mM glutathione (GSH), whereas the DOX release
      is significantly retarded in the physiological condition (PBS, pH 7.4). Confocal
      microscopic images and flow cytometry analysis demonstrated that DOX-ST-NPs were
      selectively taken up by MDA-MB-231 as the representative Trop2-expressing TNBC
      cells. Consequently, DOX-ST-NPs exhibited higher toxicity to Trop2-positive MDA
      MB-231 cancer cells, compared to DOX-loaded control nanoparticles without the
      disulfide bond or anti-Trop2 antibody. Overall, ST-NPs might be a promising
      carrier of DOX for targeted TNBC therapy.

PMID- 29055701
TI  - Self-healing and tough hydrogels with physically cross-linked triple networks
      based on Agar/PVA/Graphene.
AB  - The aim of this work was to prepare polyvinyl alcohol (PVA)/Agar/Graphene
      nanocomposite hydrogels through a one-pot and green solution mixing method using
      water as solvent. Herein a novel strategy for designing stiff, tough and self
      healing triple network (TN) hydrogels was proposed. The prepared TN hydrogels
      composed of strong Agar polysaccharide as the first network, tough PVA biopolymer
      gel as the second network, and graphene nanoplatelets as the third network.
      Interestingly, similar to natural biomaterials, all of the networks of the
      nanocomposite hydrogel were physically cross-linked via dynamic hydrogen bonding
      associations, i.e. Agar helix bundles, PVA crystallites and polymer chain
      physisorption on graphene. Therefore, the prepared hydrogels demonstrated
      simultaneous high strength, toughness, and autonomous self-healing within a short
      time of 10min, which is rare in the literature. The developed hydrogels can be a
      promising material in many biomedical applications, such as scaffolds,
      cartilages, tendons and muscles.

PMID- 29055703
TI  - Structural studies of two thermostable laccases from the white-rot fungus
      Pycnoporus sanguineus.
AB  - Laccases are enzymes that have the ability to catalyze the oxidation of a wide
      spectrum of phenolic compounds with the four-electron reduction of molecular
      oxygen to water. The active site of those proteins contains four copper ions,
      classified into three types. Laccases are interesting enzymes for study from the
      point of view of their structure, function and application because of their role
      in lignin degradation. Structural studies of two thermostable laccases produced
      by the strain Pycnoporus sanguineus CS43 (PsLacI and PsLacII) were performed.
      Both isoforms of PsLac show high thermal stability, at 60 degrees C and 50
      degrees C, respectively, and they remained active at a high concentration of
      organic solvents. However, PsLacI has a higher thermal and pH stability and
      tolerance against inhibitors, and is a more efficient catalyst for ABTS and DMP
      (laccases substrate) than PsLacII. Based on the determined crystal structures we
      achieved insights into the structural factors relevant for the enzymatic
      properties of PsLacI and PsLacII. N-glycosylation site Asn354, which is very
      often present in structures of fungal laccases from other species, was not
      present in PsLac. This observation may be of particular significance due to the
      close distance between Asn354 and the substrate-binding pocket. This results in
      better access to the hydrophobic cavity for a particular substrate. Furthermore,
      we identified significant differences in the region of substrate-binding pocket,
      which confer PsLacI a markedly better performance than PsLacII.

PMID- 29055702
TI  - Biochemical characterization and functional analysis of invertase Bmsuc1 from
      silkworm, Bombyx mori.
AB  - Invertase or beta-fructofuranosidase (EC 3.2.1.26) belongs to the glycoside
      hydrolase family 32, which catalyzes the hydrolysis of sucrose into fructose and
      glucose. Here, we report the biochemical and functional characterization of
      invertase Bmsuc1 from Bombyx mori. Bmsuc1 showed optimal hydrolysis at pH 7.0-8.0
      and its optimum temperature is 50 degrees C using sucrose as substrate. Circular
      dichroism spectra indicated Bmsuc1 had a primarily beta-strand structure. The
      thermal denaturations transition of Bmsuc1 was a cooperative process with a Tm,
      DeltaH, and DeltaS of 53.81+/-0.12 degrees C, 185.51+/-0.14KJ/mol and 0.56+/
      0.01KJ/(molK), respectively. Moreover, homology modeling and multi-sequence
      alignment suggested that Bmsuc1 has a canonical beta-propeller fold and one
      conserved catalytic triad, Asp63-Asp181-Glu234, which is located in the bottom of
      the substrate-binding pocket. Bmsuc1 was expressed at high levels in the silk
      gland at both the transcriptional and translational levels. These expression
      profiles combined with invertase activity analyses of Bmsuc1 suggested that it
      might function as a digestive enzyme to hydrolyze sugar in the silk gland lumen.
      Collectively, these findings expand towards a better understanding of the
      structure of Bmsuc1 and its function in the silk gland.

PMID- 29055704
TI  - Comparative study of the effect of different fucoidans from Sargassum maclurei
      and Saccharina japonica on FGFs/FGFR signaling activation in BaF3 cells.
AB  - Different sulfated polysaccharides have distinct abilities to activate specific
      fibroblast growth factor (FGF) signaling pathways in FGFR1c-expressing BaF3
      cells. In the current study, we first isolated and characterized different
      fucoidan fractions from Sargassum maclurei and Saccharina japonica. All of the
      fucoidan fractions were incubated with BaF3 cells in the presence of FGF-1, -2, 
      7, -8, -9, and -10, respectively, to evaluate their FGFs/FGFR1c signal-activating
      ability. Our data showed that low molecular weight fucoidan fraction from S.
      japonica with highest sulfate content (LMWF-2M) had the most potent activity
      among all of the six tested FGFs. Low sulfated heteropolysacchairde fraction LMWF
      0.5M, along with SMP-1, SMP-D-1, and SMP-A-1, only activated the FGF-2/FGFR1c
      pair (P<0.05). In contrast, SMP, SMP-A, and SMP-D stimulated BaF3 cell
      proliferation except for FGF-8. Both LMWF-1M and LMWF-2M facilitated FGF-1-, -2-,
      -8-, and -9-based signaling. The sulfate content was the major contributing
      factor to the observed activity followed by the molecular weight. The
      monosaccharide composition also affected the activity, in that SMP and its
      derivatives with varied monosaccharide composition could not induce BaF3 cell
      proliferation in the presence of FGF-8. The structure-activity relationships
      revealed in current study provided useful information for the potential
      application of fucoidans in FGF/FGFR signaling regulation.

PMID- 29055705
TI  - Biochemical and molecular characterization of a novel metalloprotease from
      Pseudomonas fluorescens strain TBS09.
AB  - A novel extracellular protease called MPDZ was purified and characterized from
      Pseudomonas fluorescens strain TBS09. The enzymatic properties of MPDZ were
      investigated using biochemical and biophysical methods. Matrix assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis
      revealed that it was a monomer with a molecular mass of 50013.17Da. The NH2
      terminal 27 amino acid sequence of MPDZ showed high homology with those of
      Pseudomonas-proteases of the serralysin family. MPDZ showed optimal activity at
      pH 7 and 60 degrees C. It was totally inhibited by EGTA, EDTA, and 1,10
      phenanthroline, suggesting its belonging to the metalloprotease family. Because
      of the interesting properties, the mpDZ gene encoding MPDZ was cloned, sequenced,
      and expressed in E. coli. The deduced amino acid sequence showed a strong
      homology with other Pseudomonas-metalloproteases. The highest sequence identity
      value (97%) was obtained with AprX from P. fluorescens strain CY091, with only 12
      different amino acid residues. The physico-chemical properties of the
      extracellular purified recombinant enzyme (rMPDZ) were similar to those of MPDZ.
      Overall, MPDZ is bestowed with a number of promising biochemical properties that
      might give new opportunities for its biocatalytic applications. These data
      constitute an essential first step towards an understanding of the properties of
      MPDZ enzyme.

PMID- 29055707
TI  - Purification and characterization of a novel tannase produced by Kluyveromyces
      marxianus using olive pomace as solid support, and its promising role in gallic
      acid production.
AB  - Tannase is considered one of the most important industrial enzymes that find
      great applications in various sectors. Production of tannases through solid state
      fermentation (SSF) using agro-industrial wastes is an eco-friendly and cheap
      technology. Tannase was produced by the yeast Kluyveromyces marxianus using olive
      pomace as a solid support under SSF. It was purified using ammonium sulfate
      fractional precipitation followed by Sephadex G-200 gel filtration resulting in
      64.6% enzyme yield with 1026.12U/mg specific activity and 24.21 purification
      fold. Pure tannase had molecular weight of 65 KDa and 66.62 KDa by SDS-PAGE and
      gel filtration, respectively. It showed a maximal activity at 35 degrees C having
      two different pH optima, one of which is acidic (4.5) and the other one is
      alkaline (8.5). The enzyme was stable in the acidic range of pH (4.0-5.5) for
      30min, and thermostable within the temperature range 30-70 degrees C. Using
      tannic acid, the enzyme had a Km value of 0.77mM and Vmax of 263.20MUmolemin-1ml
      1. The effect of different metal ions on enzymatic activity was evaluated. HPLC
      analysis data indicated that the purified enzyme could carry out 24.65% tannic
      acid conversion with 5.25 folds increase in gallic acid concentration within
      30min only.

PMID- 29055706
TI  - Inhibitory action of dicyclomine on lipase activity, kinetics and molecular
      study.
AB  - Lipase is one of the most important groups of enzymes for industry and medicine.
      It breaks down triacylglycerol to glycerol and fatty acids. Some bacteria use
      lipase to degrade the extracellular matrix of the host cells to penetrate into
      the tissues. Dicyclomine is a muscarinic antagonist receptor that relieves the
      smooth muscle spasm of the gastrointestinal tract and affects the cardiovascular
      system. In this research, the effect of a dicyclomine on the lipase activity of
      Pseudomonas aeruginosa was studied. Hanes-Woolf plot showed that the drug
      inhibited the enzyme by competitive inhibition. The IC50 value (60uM) and Ki
      (30uM) of the drug revealed that the drug bound to enzyme with high affinity.
      Determination of enzyme activity in various temperature showed that the maximum
      activity of lipase was at 60 degrees C both in the presence and absence of the
      drug. Arrhenius plot determined that the activation energy of the enzyme reaction
      was increased in the presence of the drug. The model of binding demonstrated that
      the drug entered a pocket containing 10 amino acids and interacted by hydrogen
      bond and hydrophobic interaction and the conformational change of the enzyme
      after binding of the drug was confirmed by fluorescence measurement.

PMID- 29055708
TI  - Recent advances in the application of microbial transglutaminase crosslinking in
      cheese and ice cream products: A review.
AB  - Microbial transglutaminase (MTGase) has been currently utilized to form new food
      structures and matrices with high physicochemical stability. Incorporation of
      this multi-functional enzyme into structural composition of milk protein-based
      products, such as cheese and ice cream, can not only be a successful strategy to
      improve their nutritional and technological characteristics through
      intramolecular cross-linking, but also to reduce the production cost by
      decreasing fat and stabilizer contents. The recent research developments and
      promising results of MTGase application in producing functional formulations of
      cheese and ice cream with higher quality characteristics are reviewed. New
      interesting insights and future perspectives are also presented. The addition of
      MTGase to cheese led to significant improvements in moisture, yield, texture,
      rheology and sensory properties, without changes in the chemical composition.
      Furthermore, pH value of ice cream is not affected by the MTGase treatment.
      Compared to untreated ice creams, application of MTGase significantly promotes
      consistency, fat destabilization, overrun and organoleptic acceptance, while a
      substantial reduction in firmness and melting rate of samples was observed. The
      addition of MTGase to cheese and ice cream-milk provides reinforcement to the
      protein matrix and can be considered as a novel additive for improving the
      physicochemical and organoleptic properties of final products.

PMID- 29055709
TI  - Thioredoxin reductase from the bovine filarial parasite Setaria cervi: Studies on
      its localization and optimization of the extraction.
AB  - Exploration of novel drug targets has been the major thrust area in filarial
      research. In this regard, identification and characterization of oxidative
      enzymes that play pivotal role in the survival of filarial parasite inside host
      are of immense importance. In this study, we are reporting the presence of an
      important redox regulatory enzyme, thioredoxin reductase (TrxR) in the bovine
      filarial parasite Setaria cervi. TrxR was found to be exists throughout the
      developmental stages viz. oocyte, microfilaria and adult of the parasite. Since
      further studies on this enzyme require adequate quantity, influential extraction
      parameters were optimized statistically using response surface methodology (RSM)
      employing a seven factors based Box-Behnken design matrix. ANOVA analysis
      revealed the relative importance of each parameter and a regression equation was
      eventually developed that could predict the specific activity (SA) of TrxR.
      Finally the optimized extraction conditions predicted by RSM was 6.1ml of 61.86mM
      buffer, pH 6.0, with extraction temperature 39.96 degrees C for 180min in
      addition to 450rpm agitation and 20MUl/ml of protease inhibitor. Therefore this
      study is going to be the maiden report depicting the identity of TrxR in filarial
      parasite and the optimized extraction conditions for its isolation with better
      kinetic efficiency.

PMID- 29055710
TI  - Remote Ischemic Preconditioning in High-risk Cardiovascular Surgery Patients: A
      Randomized-controlled Trial.
AB  - Remote ischemic preconditioning (RIPC) may reduce biomarkers of ischemic injury
      after cardiovascular surgery. However, it is unclear whether RIPC has a positive
      impact on clinical outcomes. We performed a blinded, randomized controlled trial
      to determine if RIPC resulted in fewer adverse clinical outcomes after cardiac or
      vascular surgery. The intervention consisted of 3 cycles of RIPC on the upper
      limb for 5 minutes alternated with 5 minutes of rest. A sham intervention was
      performed on the control group. Patients were recruited who were undergoing (1)
      high-risk cardiac or vascular surgery or (2) cardiac or vascular surgery and were
      at high risk of ischemic complications. The primary end point was a composite
      outcome of mortality, myocardial infarction, stroke, renal failure, respiratory
      failure, and low cardiac output syndrome, and the secondary end points included
      the individual outcome parameters that made up this score, as well as troponin-I
      values. A total of 436 patients were randomized and analysis was performed on 215
      patients in the control group and on 213 patients in the RIPC group. There were
      no differences in the composite outcome between the 2 groups (RIPC: 67 [32%] and
      control: 72 [34%], relative risk [0.94 {0.72-1.24}]) or in any of the individual
      components that made up the composite outcome. Additionally, we did not observe
      any differences between the groups in troponin-I values, the length of intensive
      care unit stay, or the total hospital stay. RIPC did not have a beneficial effect
      on clinical outcomes in patients who had cardiovascular surgery.

PMID- 29055711
TI  - Comparison of del Nido and St Thomas Cardioplegia Solutions in Pediatric
      Patients: A Prospective Randomized Clinical Trial.
AB  - We conducted a prospective randomized trial to compare del Nido (DN) cardioplegia
      with conventional cold blood cardioplegia (St Thomas [STH]) in pediatric
      patients. We randomized 100 pediatric patients aged <=12 years undergoing
      elective repair of ventricular septal defects and tetralogy of Fallot to the DN
      and the STH groups. In the DN group, a 20 mL/kg single dose was administered. In
      the STH group, a 30 mL/kg dose was administered, followed by repeated doses at 25
      to 30-minute intervals. The primary outcome was cardiac index that was measured
      4 times intra- and postoperatively. Troponin-I, interleukin-6, and tissue
      necrosis factor-alpha were measured. Myocardial biopsy was obtained to assess
      electron-microscopic ultrastructural changes. Cardiac indices were significantly
      higher in the DN group than in the STH group 2 hours after termination of
      cardiopulmonary bypass (P = 0.0006), after 6 hours (P = 0.0006), and after 24
      hours (P <= 0.0001). On repeated measure regression analysis, the cardiac index
      was on an average 0.50 L/min/m2 higher in the DN group than in the STH group at
      any time point (P = 0.002). Duration of mechanical ventilation (P = 0.01),
      intensive care unit stay (P = 0.01), and hospital stay (P = 0.0007) was
      significantly lower in the DN group. Patients in the DN group exhibited lower
      troponin-I release 24 hours following cardiopulmonary bypass (P = 0.021).
      Electron microscopic studies showed more myofibrillar disarray in the STH group
      (P = 0.02). Use of long-acting DN cardioplegia solution was associated with
      better preservation of cardiac index, lesser troponin-I release, and decreased
      morbidity. Ultrastructural changes showed better preservation of myofibrillar
      architecture.

PMID- 29055712
TI  - A decade of RNA virus metagenomics is (not) enough.
AB  - It is hard to overemphasize the role that metagenomics has had on our recent
      understanding of RNA virus diversity. Metagenomics in the 21st century has
      brought with it an explosion in the number of RNA virus species, genera, and
      families far exceeding that following the discovery of the microscope in the 18th
      century for eukaryotic life or culture media in the 19th century for bacteriology
      or the 20th century for virology. When the definition of success in organism
      discovery is measured by sequence diversity and evolutionary distance, RNA
      viruses win. This review explores the history of RNA virus metagenomics, reasons
      for the successes so far in RNA virus metagenomics, and methodological concerns.
      In addition, the review briefly covers clinical metagenomics and environmental
      metagenomics and highlights some of the critical accomplishments that have
      defined the fast pace of RNA virus discoveries in recent years. Slightly more
      than a decade in, the field is exhausted from its discoveries but knows that
      there is yet even more out there to be found.

PMID- 29055713
TI  - Decrypting the PAK4 transcriptome profile in mammary tumor forming cells using
      Next Generation Sequencing.
AB  - The p-21 Activated Kinase 4 (PAK4) protein kinase is implicated in many cancers,
      including breast cancer. Overexpression of PAK4 is sufficient to cause mouse
      mammary epithelial cells (iMMECs) to become tumorigenic. To gain insight into the
      long-term gene expression changes that occur downstream to PAK4, we performed
      Next Generation Sequencing of RNA collected from PAK4 overexpressing iMMECs and
      wild-type iMMECs. We identified a list of genes whose expression levels were
      altered in response to PAK4 overexpression in iMMECs. Some of these genes,
      including FoxC2 and ParvB, are consistent with a role for PAK4 in cancer. In
      addition, PAK4 regulates many genes that are frequently associated with the
      inflammatory response, raising the possibility that there is a connection between
      PAK4, inflammation, and the tumor microenvironment. This study delineates the
      PAK4 transcriptome profile in transformed mammary cells and can provide
      translational utility in other types of cancers as well.

PMID- 29055714
TI  - Psychophysiology of proactive and reactive relational aggression.
AB  - This study investigated the joint effects of parasympathetic and sympathetic
      nervous system reactivity to social and non-social stressors on proactive (i.e.,
      goal-directed, unemotional) and reactive (i.e., emotional, impulsive) functions
      of relational aggression. Two hundred and forty-seven (Mage=18.77years)
      participants completed a series of stressor tasks while their sympathetic arousal
      (i.e., skin conductance) and parasympathetic arousal (i.e., respiratory sinus
      arrhythmia) were assessed. Participants also provided self-reports of their
      aggressive behavior. In the standardized social stressor only, physiological
      reactivity was related to aggression, such that respiratory sinus arrhythmia
      augmentation predicted proactive relational aggression whereas heightened skin
      conductance reactivity predicted reactive relational aggression. Finally, in the
      context of low skin conductance reactivity, respiratory sinus arrhythmia
      augmentation was related to heightened proactive and reactive aggression, whereas
      respiratory sinus arrhythmia withdrawal was protective. Results suggest that the
      benefits hypothesized to accompany respiratory sinus arrhythmia withdrawal may
      only occur among individuals with low "fight or flight" stress responses.
      Findings extend research on the physiological indicators of aggression to
      relational aggression, and highlight the importance of assessing functions of
      aggression, as well as physiological reactivity to multiple stressors.

PMID- 29055715
TI  - Live or let die: Neuroprotective and anti-cancer effects of nutraceutical
      antioxidants.
AB  - Diet sources are closely involved in the pathogenesis of diverse neuropsychiatric
      disorders and cancers, in addition to inherited factors. Currently, natural
      products or nutraceuticals (commonly called medical foods) are increasingly
      employed for adjunctive therapy of these patients. However, the potential
      molecular mechanisms of the nutrient efficacy remain elusive. In this review, we
      summarized the neuroprotective and anti-cancer mechanisms of nutraceuticals. It
      was concluded that the nutraceuticals exerted neuroprotection and suppressed
      tumor growth possibly through the differential modulations of redox homeostasis.
      In addition, the balance between reactive oxygen species (ROS) production and ROS
      elimination was manipulated by multiple molecular mechanisms, including cell
      signaling pathways, inflammation, transcriptional regulation and epigenetic
      modulation, which were involved in the therapeutic potential of nutraceutical
      antioxidants against neurological diseases and cancers. We specifically proposed
      that ROS scavenging was integral in the neuroprotective potential of
      nutraceuticals, while alternation of ROS level (either increase or decrease) or
      disruption of redox homeostasis (ROS addiction) constituted the anti-cancer
      property of these compounds. We also hypothesized that ROS-associated
      ferroptosis, a novel type of lipid ROS-dependent regulatory cell death, was
      likely to be a critical mechanism for the nutraceutical antioxidants. Targeting
      ferroptosis is advantageous to develop new nutraceuticals with more effective and
      lower adverse reactions for curing patients with neuropsychiatric diseases or
      carcinomas.

PMID- 29055716
TI  - Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a
      connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve
      injured mice.
AB  - Connexin43 (Cx43) hemichannels in spinal cord astrocytes are implicated in the
      maintenance of neuropathic pain following peripheral nerve injury. Peptide5 is a
      Cx43 mimetic peptide that blocks hemichannels. In this study, we investigated the
      effects of spinal delivery of Peptide5 on mechanical pain hypersensitivity in two
      mouse models of neuropathic pain, peripheral nerve injury and chemotherapy
      induced peripheral neuropathy (CIPN). We demonstrated that 10days following a
      chronic constriction injury (CCI) of the sciatic nerve, Cx43 expression, co
      localised predominantly with astrocytes, was increased in the ipsilateral L3-L5
      lumbar spinal cord. An intrathecal injection of Peptide5 into nerve-injured mice,
      on day 10 when pain was well-established, caused significant improvement in
      mechanical pain hypersensitivity 8h after injection. Peptide5 treatment resulted
      in significantly reduced Cx43, and microglial and astrocyte activity in the
      dorsal horn of the spinal cord, as compared to control saline-treated CCI mice.
      Further in vitro investigations on primary astrocyte cultures showed that 1h pre
      treatment with Peptide5 significantly reduced adenosine triphosphate (ATP)
      release in response to extracellular calcium depletion. Since ATP is a known
      activator of the NOD-like receptor protein 3 (NLRP3) inflammasome complex, a key
      mediator of neuroinflammation, we examined the effects of Peptide5 treatment on
      NLRP3 inflammasome expression. We found that NLRP3, its adaptor apoptosis
      associated spec-like protein (ASC) and caspase-1 protein were increased in the
      ipsilateral spinal cord of CCI mice and reduced to naive levels following
      Peptide5 treatment. In the models of oxaliplatin- and paclitaxel-induced
      peripheral neuropathy, treatment with Peptide5 had no effect on mechanical pain
      hypersensitivity. Interestingly, in these CIPN models, although spinal Cx43
      expression was significantly increased at day 13 following chemotherapy, NLRP3
      expression was not altered. These results suggest that the analgesic effect of
      Peptide5 is specifically achieved by reducing NLRP3 expression. Together, our
      findings demonstrate that blocking Cx43 hemichannels with Peptide5 after nerve
      injury attenuates mechanical pain hypersensitivity by specifically targeting the
      NLRP3 inflammasome in the spinal cord.

PMID- 29055717
TI  - Development of 3D culture models of plexiform neurofibroma and initial
      application for phenotypic characterization and drug screening.
AB  - Plexiform neurofibromas (PNs), which may be present at birth in up to half of
      children with type 1 neurofibromatosis (NF1), can cause serious loss of function,
      such as quadriparesis, and can undergo malignant transformation. Surgery is the
      first line treatment although the invasive nature of these tumors often prevents
      complete resection. Recent clinical trials have shown promising success for some
      drugs, notably selumetinib, an inhibitor of MAP kinase kinase (MEK). We have
      developed three-dimensional (3D) cell culture models of immortalized cells from
      NF1 PNs and of control Schwann cells (SCs) that we believe mimic more closely the
      in vivo condition than conventional two-dimensional (2D) cell culture. Our goal
      is to facilitate pre-clinical identification of potential targeted therapeutics
      for these tumors. Three drugs, selumetinib (a MEK inhibitor), picropodophyllin
      (an IGF-1R inhibitor) and LDN-193189 (a BMP2 inhibitor) were tested with dose
      response design in both 2D and 3D cultures for their abilities to block net cell
      growth. Cell lines grown in 3D conditions showed varying degrees of resistance to
      the inhibitory actions of all three drugs. For example, control SCs became
      resistant to growth inhibition by selumetinib in 3D culture. LDN-193189 was the
      most effective drug in 3D cultures, with only slightly reduced potency compared
      to the 2D cultures. Characterization of these models also demonstrated increased
      proteolysis of collagen IV in the matrix by the PN driver cells as compared to
      wild-type SCs. The proteolytic capacity of the PN cells in the model may be a
      clinically significant property that can be used for testing the ability of drugs
      to inhibit their invasive phenotype.

PMID- 29055718
TI  - Online detection of amplitude modulation of motor-related EEG desynchronization
      using a lock-in amplifier: Comparison with a fast Fourier transform, a continuous
      wavelet transform, and an autoregressive algorithm.
AB  - BACKGROUND: Neurofeedback of event-related desynchronization (ERD) in
      electroencephalograms (EEG) of the sensorimotor cortex (SM1) using a brain
      computer interface (BCI) paradigm is a powerful tool to promote motor recovery
      from post-stroke hemiplegia. However, the feedback delay attenuates the degree of
      motor learning and neural plasticity. NEW METHOD: The present study aimed to
      shorten the delay time to estimate amplitude modulation of the motor-imagery
      related alpha and beta SM1-ERD using a lock-in amplifier (LIA) algorithm. The
      delay time was evaluated by calculating the value of the maximal correlation
      coefficient (MCC) between the time-series trace of ERDs extracted by the online
      LIA algorithm and those identified by an offline algorithm with the Hilbert
      transform (HT). RESULTS: The MCC and delay values used to estimate the ERDs
      calculated by the LIA were 0.89+/-0.032 and 200+/-9.49ms, respectively.
      COMPARISON WITH EXISTING METHOD(S): The delay time and MCC values were
      significantly improved compared with those calculated by the conventional fast
      Fourier transformation (FFT), continuous Wavelet transformation (CWT), and
      autoregressive (AR) algorithms. Moreover, the coefficients of variance of the
      delay time and MCC values across trials were significantly lower in the LIA
      compared with the FFT, CWT, and AR algorithms. CONCLUSIONS: These results
      indicate that the LIA improved the detection delay, accuracy, and stability for
      estimating amplitude modulation of motor-related SM1-ERD. This would be
      beneficial for BCI paradigms to facilitate neurorehabilitation in patients with
      motor deficits.

PMID- 29055719
TI  - Functional brain connectivity in resting-state fMRI using phase and magnitude
      data.
AB  - BACKGROUND: The output of BOLD fMRI consists of a pair of magnitude and phase
      components. While the magnitude data has been widely accepted for brain function
      analysis, we can also make use of the phase data (unwrapped) since this is a good
      representation of the internal magnetic field. In this work, we discuss the use
      of fMRI phase data for brain function analysis. NEW METHODS: The fMRI phase data
      taken from 100 subjects are preprocessed using standard SPM approaches. Group
      independent component analysis (ICA) is applied to the magnitude and phase data
      separately. We then compare the spatial patterns for both magnitude and phase
      data using an empirical spatial smoothing procedure. We also evaluate the
      magnitude and phase functional network connectivity (FC) matrices. RESULTS: We
      observed the positive/negative correlation-balanced functional connectivity in
      phase data, which is distinct from the positive correlation prevalence in
      magnitude data. The phase FC (pFC) structure is quite different from the
      magnitude FC (mFC) in functional clusters (on-diagonal blocks or cliques) and
      inter-cluster couplings (off-diagonal blocks). COMPARISON WITH EXISTING: Methods
      since both the magnitude and phase data of the fMRI signals are generated from
      the same magnetic source, either can be useful for brain function analysis from
      different perspective (per different measurements). Herein, we report on making
      use of resting-state fMRI phase data for brain functional analysis in comparison
      with magnitude data. This exploration in phase fMRI may provide a new arena for
      more comprehensive brain function analysis.

PMID- 29055720
TI  - High hepatic exposure of furanocoumarins in Radix Angelica dahuricae is
      associated with transporter mediated active uptake.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Radix Angelica dahuricae (RAD), the roots of
      Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav, is a well-known
      traditional Chinese medicine (TCM) and has been used for centuries to treat
      headaches, toothaches, nose congestion, abscesses, furunculoses, and acne. This
      herb is also one of frequently reported TCMs showing the herb-drug interaction
      potential. Furanocoumarins are main bioactive components of RAD. AIM OF THE
      STUDY: This study is designed to characterize the tissue distribution profiles of
      furanocoumarins after oral administration of RAD extract in rats and to explore
      the mechanism underlying the high hepatic exposure of the major furanocoumarins.
      MATERIALS AND METHODS: The tissue distribution of nine furanocoumarins was
      determined in rats after an oral dose of 0.46g/kg RAD extract using high
      performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Unbound
      fractions (fu) of major furanocoumarins, including imperatorin (IM),
      isoimperatorin (IIM), bergapten (BER) and oxypeucedanin hydrate (OXYH), were
      measured in rat plasma and selected tissue homogenates (liver, kidney, lung and
      brain) with Rapid Equilibrium Dialysis (RED) method. The temperature dependent
      hepatic uptake of IM, IIM, BER and OXYH were evaluated in suspended rat primary
      hepatocytes at 4 degrees C or 37 degrees C by the oil-spin method. The uptake
      kinetics was conducted in the cells over a wide concentration range. The
      furanocoumarins were co-incubated with a panel of transporter inhibitors to
      investigate the involvement of uptake transporters in the hepatic uptake. The
      transcellular transport characteristics of IM, IIM, BER and OXYH were further
      assessed using Caco-2 cell monolayer model. RESULTS: IM, IIM, BER and OXYH were
      found to be the major bioactive furanocoumarins in rat plasma and tissues,
      representing more than 90% exposure for all the detected furanocoumarins. The
      most concentrative organ of major furanocoumarins was the liver, with liver-to
      plasma exposure ratio (Kp,AUC) of 5.1, 6.5 and 4.7 for IM, IIM and BER, and 2.3
      for OXYH, respectively. IM, IIM and BER also showed higher concentrations in the
      kidney with Kp above 2.2. The higher protein binding of the furanocoumarins
      partially contributed to their higher tissue exposure. In suspended rat primary
      hepatocyte, the hepatic uptake of IM, IIM, BER and OXYH was temperature
      dependent, with considerably higher uptake at 37 degrees C than at 4 degrees C.
      Uptake kinetics indicated that the hepatic uptake of IM, IIM, BER and OXYH
      involved both active transport and passive diffusion processes. For IM, IIM and
      BER, the contribution of the active transport was greater than the passive
      process, with the CLactive/CLuptake > 72%. Ritonavir (RTN) and cyclosporine A
      (CsA), the known inhibitors of organic anion transporting polypeptide (Oatp)
      significantly inhibited the hepatic uptake of IM and BER, while the inhibitor of
      the organic anion transporters (Oat) probenecid (PBC) remarkably reduced IIM
      uptake. In the Caco-2 cell model, the furanocoumarins were highly permeable in
      the apical to basolateral direction without notable active efflux. CONCLUSION:
      The furanocoumarins rapidly and widely distributed into various tissues after
      oral dose of the RAD extract. IM, IIM, BER and OXYH were the major components
      detected in both plasma and tissues. Liver was the most distributed tissue of the
      total and free furanocoumarins. Non-specific protein binding contributed
      partially to the higher tissue exposures of these bioactive components. The Oatp
      and Oat mediated active uptake played the primal role in the high hepatic
      exposure of the furanocoumarins.

PMID- 29055721
TI  - The essential oil from Citrus limetta Risso peels alleviates skin inflammation:
      In-vitro and in-vivo study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Citrus fruit peels are traditionally used in folk
      medicine for the treatment of skin disorders but it lacks proper pharmacological
      intervention. Citrus limetta Risso (Rutaceae) is an important commercial fruit
      crops used by juice processing industries in all continents. Ethnopharmacological
      validation of an essential oil isolated from its peels may play a key role in
      converting the fruit waste materials into therapeutic value added products. AIM
      OF THE STUDY: To evaluate the chemical and pharmacological (in-vitro and in-vivo)
      profile of essential oil isolated from Citrus limetta peels (Clp-EO) against skin
      inflammation for its ethnopharmacological validation. MATERIALS AND METHODS:
      Hydro-distilled essential oil extracted from Citrus limetta peels (Clp-EO) was
      subjected to gas chromatography (GC) analysis for identification of essential oil
      constituents and its anti-inflammatory evaluation through in vitro and in vivo
      models. RESULTS: Chemical fingerprint of Clp-EO revealed the presence of
      monoterpene hydrocarbon and limonene is the major component. Pre-treatment of Clp
      EO to the macrophages was able to inhibit the production of pro-inflammatory
      cytokines (TNF-alpha, IL-6, IL-1beta) in LPS-induced inflammation as well as the
      production of reactive oxygen species (ROS) in H2O2-induced oxidative stress. In
      in-vivo study, topical application of Clp-EO was also able to reduce the 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced ear thickness, ear weight, lipid
      peroxidation, pro-inflammatory cytokines production and ameliorate the
      histological damage in the ear tissue. In-vitro and in-vivo toxicity study
      indicate that it is safe for topical application on skin. CONCLUSION: These
      findings suggested the preventive potential of Clp-EO for the treatment of
      inflammation linked skin diseases.

PMID- 29055722
TI  - Study of insulin vascular sensitivity in aortic rings and endothelial cells from
      aged rats subjected to caloric restriction: Role of perivascular adipose tissue.
AB  - The prevalence of metabolic syndrome is dramatically increasing among elderly
      population. Metabolic syndrome in aged individuals is associated with
      hyperinsulinemia and insulin resistance both in metabolic tissues and in the
      cardiovascular system, with this fact being associated with the cardiometabolic
      alterations associated to this condition. Caloric restriction (CR) improves
      insulin sensitivity and is one of the dietetic strategies most commonly used to
      enlarge life and to prevent aging induced cardiovascular alterations. The aim of
      this study was to analyze the possible beneficial effects of CR in aging-induced
      vascular insulin resistance both in aortic rings and in primary culture of
      endothelial cells. In addition, the inflammatory profile of perivascular adipose
      tissue (PVAT) and its possible role in the impairment of vascular insulin
      sensitivity associated with aging was also assessed. Three experimental groups of
      male Wistar rats were used: 3 (3m), 24 (24m) fed ad libitum and 24months old rats
      subjected to 20% CR during their three last months of life (24m-CR). Aorta rings
      surrounded or not by PVAT were mounted in an organ bath and precontracted with
      phenylephrine (10-7.5M). Changes in isometric tension were recorded in response
      to cumulative insulin concentrations (10-8-10-5.5M) in the presence or absence of
      L-NAME (10-4M). Aortic rings and primary aortic endothelial cells were incubated
      in presence/absence of insulin (10-7M) and the activation of the PI3K/Akt and
      MAPK pathways as well as nitrite and nitrates concentrations and the mRNA levels
      of eNOS, insulin receptor, and GLUT-4 were assessed. CR prevented the aging
      induced decrease in the vasodilator response to insulin and the aging-induced
      increase in the vasoconstrictor response to high insulin concentrations. Changes
      between 24m and 24m-CR aorta rings were abolished in the presence of L-NAME. CR
      induced-improvement in insulin vascular sensitivity was related with activation
      of the PI3K/Akt both in aortic rings and in aortic endothelial cells in response
      to insulin. CR attenuated the overexpression of iNOS, TNF-alpha and IL-1beta in
      the PVAT of aged rats although aortic rings surrounded by PVAT from 24m rats
      showed and increased vasorelaxation in response to insulin compared to aortic
      rings from 3m and 24m-CR rats. In conclusion, a moderate protocol of CR improves
      insulin vascular sensitivity and prevents the aging induced overexpression of pro
      inflammatory cytokines in PVAT.

PMID- 29055723
TI  - Proteomics and metabolomics characterizing the pathophysiology of adaptive
      reactions to the metabolic challenges during the transition from late pregnancy
      to early lactation in dairy cows.
AB  - : The transition from late pregnancy to early lactation is a critical period in a
      dairy cow's life due to the rapidly increasing drain of nutrients from the
      maternal organism towards the foetus and into colostrum and milk. In order to
      cope with the challenges of parturition and lactation, comprehensive adaptive
      reactions comprising the endocrine and the immune system need to be accomplished.
      There is high variation in this coping ability and both metabolic and infectious
      diseases, summarized as "production diseases", such as hypocalcaemia (milk
      fever), fatty liver syndrome, laminitis and ketosis, may occur and impact
      welfare, productive lifespan and economic outcomes. Proteomics and metabolomics
      have emerged as valuable techniques to characterize proteins and metabolite
      assets from tissue and biological fluids, such as milk, blood and urine. In this
      review we provide an overview on metabolic status and physiological changes
      during the transition period and the related production diseases in dairy cows,
      and summarize the state of art on proteomics and metabolomics of biological
      fluids and tissues involved in metabolic stress during the peripartum period. We
      also provide a current and prospective view of the application of the recent
      achievements generated by omics for biomarker discovery and their potential in
      diagnosis. BIOLOGICAL SIGNIFICANCE: For high-yielding dairy cows there are
      several "occupational diseases" that occur mainly during the metabolic challenges
      related to the transition from pregnancy to lactation. Such diseases and their
      sequelae form a major concern for dairy production, and often lead to early
      culling of animals. Beside the economical perspective, metabolic stress may
      severely influence animal welfare. There is a multitude of studies about the
      metabolic backgrounds of such so called production diseases like ketosis, fatty
      liver, or hypocalcaemia, although the investigations aiming to assess the
      complexity of the pathophysiological reactions are largely focused on gene
      expression, i.e. transcriptomics. For extending the knowledge towards the
      proteome and the metabolome, the respective technologies are of increasing
      importance and can provide an overall view of how dairy cows react to metabolic
      stress, which is needed for an in-depth understanding of the molecular mechanisms
      of the related diseases. We herein review the current findings from studies
      applying proteomics and metabolomics to transition-related diseases, including
      fatty liver, ketosis, endometritis, hypocalcaemia and laminitis. For each
      disease, a brief overview of the up to date knowledge about its pathogenesis is
      provided, followed by an insight into the most recent achievements on the
      proteome and metabolome of tissues and biological fluids, such as blood serum and
      urine, highlighting potential biomarkers. We believe that this review would help
      readers to be become more familiar with the recent progresses of molecular
      background of transition-related diseases thus encouraging research in this
      field.

PMID- 29055724
TI  - Exercise-induced changes in EEG alpha power depend on frequency band definition
      mode.
AB  - In the majority of studies investigating cortical alpha oscillations the alpha
      frequency is defined as a fixed band thus, neglecting recommendations in the EEG
      literature to adjust the alpha band according to the individual alpha peak
      frequency (iAPF). Based on our previous findings indicating exhaustive exercise
      induces an increase of the post-exercise iAPF, we scrutinized the influence of
      exercise on post-exercise alpha power by comparing fixed and iAPF-adjusted alpha
      frequency bands. Resting EEG was recorded from 13 scalp locations in nine
      subjects before, immediately after as well as ten minutes following an exhaustive
      exercise protocol on a cycle ergometer. Lower and upper band alpha power was
      calculated for fixed and iAPF-adjusted frequency bands. Post-exercise lower alpha
      power increased in both fixed and individually defined bands while a higher upper
      alpha power was only observed in the fixed frequency band condition. Further, the
      increase in iAPF was positively related to the changes in fixed-band upper alpha
      power. It is concluded that lower alpha power is significantly increased
      following exhaustive exercise whereas the results for upper alpha power are
      substantially influenced by the method of frequency band definition. Therefore,
      caution is indicated when analyzing and interpreting exercise-induced changes in
      alpha power.

PMID- 29055725
TI  - Evaluation of prolonged administration of isoflurane on cerebral blood flow and
      default mode network in macaque monkeys anesthetized with different maintenance
      doses.
AB  - OBJECT: Isoflurane is a commonly used volatile anesthetic agent in clinical
      anesthesia and biomedical research. Prior study suggested the cerebral blood flow
      (CBF) and default mode network (DMN) could be changed after prolonged
      administration of isoflurane. The normal maintenance doses of isoflurane may vary
      from light (~0.75%) to deep (~1.5 or 2%) anesthesia. However, it is not clear how
      the duration effects are affected by the altered doses. The present study is
      aimed to examine if the duration effects are affected when isoflurane
      concentration is altered within normal maintenance doses. MATERIALS AND METHODS:
      Adult rhesus monkeys (n=5, 8-12 years old, 8-10kg) were anesthetized and
      maintained at isoflurane levels 0.89+/-0.03%, 1.05+/-0.12%, or 1.19+/-0.08%. CBF
      and DMN of monkeys were examined using arterial spin-labeling perfusion and
      resting state functional MRI techniques. RESULTS: the functional connectivity
      (FC) in the dominant DMN (posterior cingulate cortex (PCC) to anterior cingulated
      cortex (ACC) or media prefrontal cortex (MPFC)) decreased substantially and
      similarly during 4-h administration of isoflurane at any given maintenance
      dosage. CBF changes varied with isoflurane dosage. At the low dose (~0.89%), CBF
      decreased in most brain regions. In contrast, no obvious changes was seen in
      those regions (except for the subcortex) when higher doses of isoflurane were
      applied. CONCLUSION: FC in DMN was reduced substantially during prolonged
      administration of isoflurane. The FC reduction was not varying significantly with
      maintenance doses of isoflurane but the duration effect on CBF was dose
      dependent. Such duration effects of isoflurane administration on DMN and CBF
      should be considered in the interpretation of the outcome in related neuroimaging
      studies of anesthetized subjects.

PMID- 29055726
TI  - Copper-mediated on-off control of gene expression in filamentous fungus
      Trichoderma reesei.
AB  - We developed a copper-mediated gene expression on-off control system and an
      unmarked genetic modification strategy based on the modified copper responsive
      promoter Ptcu1c from the filamentous fungus Trichoderma reesei. The molecular
      tool for the gene expression on-off control can be used to manipulate many
      biological processes in T. reesei.

PMID- 29055727
TI  - Popeye sign: Tenodesis vs. self-locking "T" tenotomy of the long head of the
      biceps.
AB  - INTRODUCTION: Treatment of long head of the biceps lesions is controversial. A
      new technique of self-locking "T" tenotomy was developed in our department in
      2013. HYPOTHESIS: The main objective of the present study was to assess onset of
      Popeye sign after "T" tenotomy, with comparison to long head of the biceps
      tenodesis. MATERIAL AND METHODS: A continuous retrospective study included 180
      patients with long head of the biceps lesion, either isolated or associated with
      rotator cuff tear. RESULTS: 130 underwent "T" tenotomy (group A), and 50
      tenodesis (group B). Mean age was 57.9 years (range, 23-88 years) in group A and
      50.8 years (range, 20-66 years) in group B. At last follow-up, 27.7% of patients
      in group A and 24% in group B showed Popeye sign (P=0.616), after equivalence
      test and adjustment on age and occupational activity. Bicipital groove pain was
      more frequent in the tenodesis group (44% versus 25.4%; P=0.025). DISCUSSION:
      Self-locking "T" tenotomy did not significantly differ from tenodesis in onset of
      Popeye sign or clinical results, and showed better postoperative course. LEVEL OF
      EVIDENCE: IV, retrospective study.

PMID- 29055728
TI  - Ahmed glaucoma valve in various etiologies of refractory glaucoma: Surgical
      outcomes and success factors.
AB  - PURPOSE: To study the epidemiology and mid-term results of the Ahmed glaucoma
      valve (AGV) in various etiologies of refractory glaucoma in a Lebanese center,
      and to assess complications and factors that influence the surgical success rate.
      METHODS: In this retrospective epidemiological study, we reviewed 108 eyes with
      refractory glaucoma that underwent an AGV implantation in a tertiary care center
      in Lebanon between January 2002 and August 2014. Findings including best
      corrected visual acuity (BCVA), intra-ocular pressure (IOP), number of
      antiglaucoma medications, factors influencing the surgical outcome, success rate
      and complications were also reviewed. RESULTS: The mean duration of follow-up was
      29.85+/-21.45 months [range, 3-60 months]. As in other Arab countries and
      compared to the rest of the world, the rate of neovascular glaucoma (NVG) was
      particularly high, occurring in 63 eyes (58.3%), and represented the primary
      cause of refractory glaucoma. Mean IOP was significantly reduced to 17.97+/
      7.35mmHg at the last follow-up visit (P<0.05). Similarly, a significant decrease
      was noted in the number of antiglaucoma medications (P<0.05). The surgical
      success rate, defined as a postoperative IOP<21, was significantly higher
      (62.0%), in older patients, those with baseline BCVA<=2 LogMAR and those with a
      history of hypertension (P<0.01). Hyphema was the most noted complication.
      CONCLUSION: The AGV is a safe and effective procedure for lowering IOP in
      refractory glaucoma patients, with hyphema being the most frequent complication.
      Both the presence of hyperstension and initial BCVA<=2 LogMAR seem to increase
      the success rate of the procedure. NVG remains the most common etiology for
      implantation, probably due to uncontrolled diabetes in the Middle East and North
      Africa.

PMID- 29055729
TI  - Central retinal artery occlusion without underlying chronic ocular ischemic
      syndrome may lead to neovascular glaucoma.
AB  - INTRODUCTION: The prevalence and etiology of neovascular glaucoma (NVG) as a
      complication of central retinal artery occlusion (CRAO) is a debated issue.
      According to some authors, NVG associated with CRAO always involves underlying
      chronic ocular ischemic syndrome (COIS) as a primum movens for CRAO. However, we
      describe 5 cases of NVG following CRAO with no underlying COIS, confirmed by
      carotid Doppler studies and ultrasound color Doppler imaging (USCDI) of the
      ophthalmic artery (OA). MATERIAL AND METHODS: We conducted a single-center
      retrospective analysis of the medical records of 5 consecutive patients who
      developed NVG following non-arteritic CRAO between July 2010 and July 2014.
      RESULTS: Five patients were included. All 5 patients were examined at the
      emergency room. The 5 patients had normal intraocular pressure and no intraocular
      neovascularization upon initial examination. They had no hemodynamically
      significant internal carotid artery stenosis, and the ophthalmic artery USCDI was
      normal. These 5 patients developed NVG subsequently to the CRAO. CONCLUSIONS: In
      our patients, carotid Doppler studies and USCDI of the OA ruled out COIS. Thus,
      COIS did not cause the NVG. CRAO may therefore lead to neovascular glaucoma
      without underlying COIS.

PMID- 29055731
TI  - [Malignant conjunctival melanoma arising from conjunctival melanosis of Reese].

PMID- 29055730
TI  - [Management of wet AMD in France in 2015].
AB  - PURPOSE AND CONTEXT: Intravitreal administration of anti-VEGF agents, available
      in France since 2007, allows stabilization and improvement in visual acuity in
      wet age-related macular degeneration (AMD). In the past few years, the management
      of this disease has evolved in terms of both diagnostic methods and treatment
      schedules, which have been adapted to the pathophysiology of AMD. The goal of
      this survey, performed in a representative sample of French ophthalmologists, was
      to describe the evolution of medical practices one year after a similar survey
      (Masse et al., J Fr Ophtalmol 2016; 39: 40-7). METHOD: The survey was performed
      from December, 2014 to March, 2015 in 191 ophthalmologists (53 general
      ophthalmologists and 98 retina specialists) with an on-line questionnaire. This
      questionnaire was designed by a committee of ophthalmologists to describe
      practices concerning screening, diagnosis, treatment and follow-up of wet AMD.
      RESULTS: An initial intravitreal injection of an anti-VEGF agent was usually
      performed within 10 days after the diagnosis of wet AMD by 98% of
      ophthalmologists and within 5 days by 63%. The treatment protocols favored by
      retina specialists were pro re nata (PRN) for 58%, Observe and Plan for 25% and
      Treat and Extend for 17%. Bilateral intravitreal injections were performed on the
      same day by 46% of retina specialists, mostly for the convenience of the patient
      and because of the low infectious risk. The initial protocol was maintained by
      one third of retina specialists throughout the course of treatment, while two
      thirds of them reported that they reassessed the protocol on average after 5
      months. CONCLUSION: This survey on the practices of the ophthalmologists in wet
      AMD highlights an improvement in the time course of patient management and an
      evolution of treatment schedules toward individualized protocols.

PMID- 29055732
TI  - Gamma scintigraphic pulmonary deposition study of glycopyrronium/formoterol
      metered dose inhaler formulated using co-suspension delivery technology.
AB  - This gamma scintigraphy imaging study was the first to assess pulmonary and
      extrathoracic deposition and regional lung deposition patterns of a radiolabelled
      long-acting muscarinic antagonist/long-acting beta2-agonist fixed-dose
      combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10MUg
      (equivalent to glycopyrrolate/formoterol fumarate 18/9.6MUg), delivered by
      pressurized metered dose inhaler (pMDI) using novel co-suspension delivery
      technology. In this Phase I, randomized, single-centre, single-blind, single
      dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy
      male adults received two actuations of GFF pMDI (7.2/5.0MUg per actuation) and
      placebo pMDI (containing phospholipid-based porous particles without active
      pharmaceutical ingredient), both radiolabelled with 99mTc, up to 5MBq per
      actuation. Gamma scintigraphy images of lungs, stomach, head and neck were
      recorded. In addition, images of the actuators after use, collected mouth
      washings and exhalation filters were acquired. On average, 38.4% of the emitted
      dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was
      deposited in the lungs. The percentage emitted dose detected in the oropharyngeal
      and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo
      pMDI, respectively. For both treatments, <=0.25% of the emitted dose was detected
      in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for
      radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized
      central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of
      both co-suspension delivery technology formulations throughout the airways. There
      were no new or unexpected safety findings. In conclusion, both formulations were
      efficiently and uniformly deposited in the lungs with similar regional deposition
      patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator
      recovered dose.

PMID- 29055734
TI  - Development of copolymeric nanoparticles of hypocrellin B: Enhanced phototoxic
      effect and ocular distribution.
AB  - In the present work, we have developed a photosensitizer hypocrellin B (HB) and
      nano silver loaded PLGA-TPGS nanoparticles with improved singlet oxygen
      production for enhanced photodynamic effect for the efficient treatment of age
      related macular degeneration. Random copolymer (PLGA-TPGS) synthesized by ring
      opening and bulk polymerization was characterized by IR, 1H NMR and TGA analysis.
      HBS-CP-NPs prepared by nanoprecipitation techniques were spherical shaped 89.6
      753.6nm size particles with negative zeta potential. The average encapsulation
      efficiency was 84.06+/-11.43% and HB release from the HBS-CP-NPs was found to be
      biphasic with a slow release of 1.41% in the first 8h and 48.91% during 3days as
      measured by RP-HPLC. DSC thermograms indicate that HB was dispersed as amorphous
      form in HBS-CP-NPs. The ROS generation level of HBS-CP-NPs was significantly
      higher than that of HB/HB-CP-NPs. The production of 1O2 of HBS-CP-NPs has been
      assessed using EPR spectrometer. The 1O2 generating efficiency follows the order
      of nano silver>HB-CP-NPs>HBS-CP-NPs>pure HB drug solution. The superior
      phototoxic effect of HBS-CP-NPs (85.5% at 50MUM) was attained at 2h irradiation
      in A549 cells. Significant anti angiogenic effect of HBS-CP-NPs was observed in
      treated CAM embryos. Following intravenous injection of HBS-CP-NPs to rabbits,
      the maximum amount of HB was found in retina (3h), iris (9h), aqueous humour (9h)
      and vitreous humour (9h).

PMID- 29055733
TI  - QX-OH/Levobupivacaine: Fixed-dose combination to provide a long-acting
      postoperative pain of knee surgery in rodents.
AB  - Although total knee arthroplasty (TKA) is a commonly performed procedure,
      anesthetic efficacy in post-surgical pain remains an issue. Exparel (45mM
      liposome bupivacaine), a relatively long-acting local anesthetic, has shown
      efficacy in blocking peripheral nerve or periarticular infiltration to achieve
      better post-TKA analgesia. In the present work, we tested whether a fixed-dose
      combination of QX-OH (35mM) and levobupivacaine (10mM) (QX-OH/LB) could confer
      longer-lasting pain relief and reduce periarticular tissue toxicity compared to
      liposome bupivacaine (45mM) after TKA operation. In the sciatic nerve block, the
      duration of sensory block by QX-OH/LB was 2-fold higher than by liposome
      bupivacaine (median [25th, 75th percentiles], 9.83 [9.33, 10.83] hours versus
      4.83 [4.83, 5] hours; P=0.001). Liposome bupivacaine failed to improve post
      surgical travel distance and speed (P=0.373) in rats 6h after TKA surgery (versus
      saline). Similar results were observed in operated mice treated with liposome
      bupivacaine. However, QX-OH/LB increased locomotor activities markedly both in
      rats and mice at 6h post-TKA (P<0.001). In addition, there was no difference in
      the inflammatory recruitment and articular structural damage among murine models
      treated with QX-OH/LB, liposome bupivacaine and saline. In conclusion, we show
      that QX-OH/LB is a safe and long-lasting anesthetic than liposome bupivacaine in
      the post-TKA pain management in murine models.

PMID- 29055735
TI  - Sucrosomial(r) iron absorption studied by in vitro and ex-vivo models.
AB  - This paper presents a comparative evaluation of different oral ferric iron
      formulations for ability to retain Fe3+ in simulated gastric fluid (SGF), be
      internalized by cells lining intestinal epithelium, and cross it to reach the
      bloodstream. In all formulations iron was ferric pyrophosphate, the excipients
      were different types and fractions of lecithin plus sucrose esters of fatty acids
      matrix (Sideral(r) RM; PRT1; PRT2) or lecithin without sucrester (SUN).
      Dissolution kinetics of formulations in SGF was studied by USP method. The
      ability of the formulations to promote iron intestinal absorption was evaluated
      by the Caco-2 cell model, measuring cellular ferritin content, and by the excised
      rat intestine model, yielding apparent permeability parameters (Papp). All
      formulations limited iron release in SGF to <=10%. Sideral(r) RM was by far the
      most absorbed by Caco-2, as ferritin content was in the order: Sideral(r)
      RM?PRT2>PRT1>SUN>control. The Fe3+ crossing the intestinal barrier was in part
      reduced to Fe2+ by epithelial enzymes, in part it was carried by formulation
      rearrangement into nano-structures able to protect it from reduction and apt for
      internalization by epithelium cells. Papp parameters were in the order:
      Sideral(r) RM?PRT1>PRT2>SUN=control. Relevance of transepithelial Fe2+carrier,
      DMT-1, to Fe3+ transport was ruled out using a DMT-1 inhibitor. In conclusion,
      Sideral(r) RM retains iron in SGF, and is the most suitable for Fe3+
      internalization by Caco-2 cells, Fe3+ protection from enzymatic reduction and
      promotion of Fe3+ absorption across intestinal epithelium, non-mediated by DMT-1.

PMID- 29055737
TI  - Lung cancer screening and its continuous risk assessment.

PMID- 29055738
TI  - The utility of preoperative laboratories in predicting postoperative
      complications following posterolateral lumbar fusion.
AB  - BACKGROUND CONTEXT: Several studies have suggested that laboratory results have
      minimal impact on clinical decision making in surgery. Despite the widespread use
      of preoperative testing in spine surgery and the large volume of posterolateral
      lumbar fusions (PLFs) being performed each year, no study has assessed the
      ability of preoperative laboratories to predict adverse events following PLF.
      PURPOSE: The purpose of this study was to explore the relationship between
      commonly obtained preoperative laboratory results and postoperative complications
      following one- to two-level PLF. STUDY DESIGN: This is a retrospective study of
      prospectively collected data. PATIENT SAMPLE: The 2006-2013 American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was
      employed to identify all patients who underwent one- to two-level PLF. OUTCOME
      MEASURES: The outcome variables of interest were 30-day postoperative
      complications, which were assessed as major complications, minor adverse events,
      and total complications. MATERIALS AND METHODS: Demographics, comorbidities, and
      perioperative characteristics were collected for each patient. Preoperative
      laboratories included sodium, blood urea nitrogen, creatinine, albumin,
      bilirubin, serum glutamic oxaloacetic transaminase, alkaline phosphatase, white
      blood cell count, hematocrit, platelet count, prothrombin time, international
      normalized ratio, and partial thromboplastin time. Bivariate analysis and
      multivariate logistic regression modeling were used to explore the relationship
      between abnormal preoperative laboratories and the incidence of postoperative
      complications. RESULTS: After controlling for age, ASA score, length of surgery,
      and all significant comorbidities, abnormal sodium (odds ratio [OR]=2.47, 95%
      confidence interval [CI]: 1.45-4.19, p=.001) and abnormal INR (OR=2.33, 95% CI:
      1.09-4.98, p=.029) were significantly associated with the development of any
      complication. Sodium (OR=1.61, 95% CI: 1.01-2.54, p=.04) and platelets (OR=1.58,
      95% CI: 1.02-2.44, p=.04) were associated with minor complications. Meanwhile,
      creatinine (OR=1.74, 95% CI: 1.02-2.99, p=.04) and platelets (OR=1.71, 95% CI:
      1.02-2.89, p=.04) were significant predictors of major adverse events.
      CONCLUSIONS: This study represents the first attempt to assess the utility of
      preoperative laboratories in predicting postoperative complications in PLF.
      Although the majority of laboratories were not significantly associated with
      adverse events, abnormal sodium values, INR, creatinine, and platelets were shown
      to be predictive of various complications.

PMID- 29055736
TI  - Participant selection for lung cancer screening by risk modelling (the Pan
      Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm,
      prospective study.
AB  - BACKGROUND: Results from retrospective studies indicate that selecting
      individuals for low-dose CT lung cancer screening on the basis of a highly
      predictive risk model is superior to using criteria similar to those used in the
      National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We
      designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess
      the efficacy of a risk prediction model to select candidates for lung cancer
      screening, with the aim of determining whether this approach could better detect
      patients with early, potentially curable, lung cancer. METHODS: We did this
      single-arm, prospective study in eight centres across Canada. We recruited
      participants aged 50-75 years, who had smoked at some point in their life (ever
      smokers), and who did not have a self-reported history of lung cancer.
      Participants had at least a 2% 6-year risk of lung cancer as estimated by the
      PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the
      model were age, smoking duration, pack-years, family history of lung cancer,
      education level, body-mass index, chest x-ray in the past 3 years, and history of
      chronic obstructive pulmonary disease. Individuals were screened with low-dose CT
      at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary
      outcome of the study was incidence of lung cancer. This study is registered with
      ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the
      study coordinating centre and were screened for PanCan risk. 15 were duplicates,
      so 7044 participants were considered for enrolment. Between Sept 24, 2008, and
      Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a
      median follow-up of 5.5 years (IQR 3.2-6.1), 172 lung cancers were diagnosed in
      164 individuals (cumulative incidence 0.065 [95% CI 0.055-0.075], incidence rate
      138.1 per 10 000 person-years [117.8-160.9]). There were ten interval lung
      cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed
      between T0 and T1, and nine between T1 and T4. Cumulative incidence was
      significantly higher than that observed in NLST (4.0%; p<0.0001). Compared with
      593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in
      the PanCan Study were early stage (I or II; p<0.0001). INTERPRETATION: The PanCan
      model was effective in identifying individuals who were subsequently diagnosed
      with early, potentially curable, lung cancer. The incidence of cancers detected
      and the proportion of early stage cancers in the screened population was higher
      than observed in previous studies. This approach should be considered for
      adoption in lung cancer screening programmes. FUNDING: Terry Fox Research
      Institute and Canadian Partnership Against Cancer.

PMID- 29055739
TI  - Mesenchymal progenitor cells primed with pentosan polysulfate promote lumbar
      intervertebral disc regeneration in an ovine model of microdiscectomy.
AB  - BACKGROUND CONTEXT: Neural compression associated with lumbar disc herniation is
      usually managed surgically by microdiscectomy. However, 10%-20% of patients re
      present with debilitating back pain, and approximately 15% require further
      surgery. PURPOSE: Using an ovine model of microdiscectomy, the present study
      investigated the relative potential of pentosan polysulfate-primed mesenchymal
      progenitor cells (pMPCs) or MPC alone implanted into the lesion site to
      facilitate disc recovery. STUDY DESIGN: An ovine model of lumbar microdiscectomy
      was used to compare the relative outcomes of administering MPCs or pMPCs to the
      injury site postsurgery. METHODS: At baseline 3T magnetic resonance imaging (MRI)
      of 18 adult ewes was undertaken followed by annular microdiscectomy at two lumbar
      disc levels. Sheep were randomized into three groups (n=6). The injured controls
      received no further treatment. Defects of the treated groups were implanted with
      a collagen sponge and MPC (5*105 cells) or pMPC (5*105 cells). After 6 months, 3T
      MRI and standard radiography were performed. Spinal columns were dissected,
      individual lumbar discs were sectioned horizontally, and nucleus pulposus (NP)
      and annulus fibrosus (AF) regions were assessed morphologically and
      histologically. The NP and AF tissues were dissected into six regions and
      analyzed biochemically for their proteoglycans (PGs), collagen, and DNA content.
      RESULTS: Both the MPC- and pMPC-injected groups exhibited less reduction in disc
      height (p<.05) and lower Pfirrmann grades (p<=.001) compared with the untreated
      injury controls, but morphologic scores for the pMPC-injected discs were lower
      (p<.05). The PG content of the AF injury site region (AF1) of pMPC discs was
      higher than MPC and injury control AF1 (p<.05). At the AF1 and contralateral AF2
      regions, the DNA content of pMPC discs was significantly lower than injured
      control discs and MPC-injected discs. Histologic and birefringent microscopy
      revealed increased structural organization and reduced degeneration in pMPC discs
      compared with MPC and the injured controls. CONCLUSIONS: In an ovine model 6
      months after administration of pMPCs to the injury site disc PG content and
      matrix organization were improved relative to controls, suggesting pMPCs'
      potential as a postsurgical adjunct for limiting progression of disc degeneration
      after microdiscectomy.

PMID- 29055740
TI  - Percutaneous balloon kyphoplasty for the treatment of very severe osteoporotic
      vertebral compression fractures: a case-control study.
AB  - BACKGROUND CONTEXT: Controversy exists regarding percutaneous balloon kyphoplasty
      (PBK) in patients with a very severe osteoporotic vertebral compression fracture
      (vsOVCF). PURPOSE: The study was conducted to investigate the clinical and
      radiological outcomes of PBK for the treatment of vsOVCF compared with those of
      non-vsOVCF. STUDY DESIGN/SETTING: This is a retrospective, case-control study.
      PATIENT SAMPLE: A total of 167 consecutive patients (210 vertebral bodies) who
      underwent PBK for OVCF between March 2010 and January 2015 were assessed. OUTCOME
      MEASURES: Visual analog scale (VAS) scores for back pain, Korean Oswestry
      disability index (K-ODI) scores, vertebral body height variations, and kyphotic
      angles were evaluated preoperatively, postoperatively, and 1 year after
      treatment. MATERIALS AND METHODS: Patients in the non-vsOVCF group (anterior
      vertebral compression of more than two-thirds on plain radiograph) who had
      undergone PBK where compared with those in the non-vsOVCF group (compression
      between 30% and two-thirds). Clinical and radiological outcomes were compared. In
      addition, complications were evaluated. RESULTS: In total, 31 patients (33
      vertebrae) in the vsOVCF group and 136 patients (177 vertebrae) in the non-vsOVCF
      group were treated with PBK. Both groups had significant postoperative
      improvements in the clinical and radiological outcomes (VAS score, K-ODI score,
      vertebral body height variation, and kyphotic angle). There was no difference
      regarding the VAS score and the K-ODI score between the two groups at the final
      follow-up (p>.05). The cement leakage occurred frequently in the vsOVCF group (26
      vertebrae, 78.8%) than in the non-vsOVCF group (92 vertebrae, 52.0%), the
      difference was statistically significant (p<.05). But there was no case that
      showed neurologic complication or pulmonary embolism caused by cement leakage.
      The incidence of recollapse was significantly higher in the vsOVCF group (five
      vertebrae, 15.2%) than in the non-vsOVCF group (seven vertebrae, 4.0%) (p<.05).
      The incidence of an adjacent segment fracture (vsOVCF group, 6 vertebrae, 18.2%;
      non-vsOVCF group, 21 vertebrae, 11.9%) was not significantly different (p=.320).
      CONCLUSIONS: Percutaneous balloon kyphoplasty is a safe and effective procedure
      for the treatment of vsOVCF.

PMID- 29055741
TI  - Radiologically defining horizontal gaze using EOS imaging-a prospective study of
      healthy subjects and a retrospective audit.
AB  - BACKGROUND CONTEXT: As sagittal alignment of the cervical spine is important for
      maintaining horizontal gaze, it is important to determine the former for surgical
      correction. However, horizontal gaze remains poorly-defined from a radiological
      point of view. PURPOSE: The objective of this study was to establish radiological
      criteria to define horizontal gaze. STUDY DESIGN/SETTING: This study was
      conducted at a tertiary health-care institution over a 1-month period. PATIENT
      SAMPLE: A prospective cohort of healthy patients was used to determine the best
      radiological criteria for defining horizontal gaze. A retrospective cohort of
      patients without rigid spinal deformities was used to audit the incidence of
      horizontal gaze. OUTCOME MEASURES: Two categories of radiological parameters for
      determining horizontal gaze were tested: (1) the vertical offset distances of key
      identifiable structures from the horizontal gaze axis and (2) imaginary lines
      convergent with the horizontal gaze axis. MATERIALS AND METHODS: Sixty-seven
      healthy subjects underwent whole-body EOS radiographs taken in a directed
      standing posture. Horizontal gaze was radiologically defined using each
      parameter, as represented by their means, 95% confidence intervals (CIs), and
      associated 2 standard deviations (SDs). Subsequently, applying the radiological
      criteria, we conducted a retrospective audit of such radiographs (before the
      implementation of a strict radioimaging standardization). RESULTS: The mean age
      of our prospective cohort was 46.8 years, whereas that of our retrospective
      cohort was 37.2 years. Gender was evenly distributed across both cohorts. The
      four parameters with the lowest 95% CI and 2 SD were the distance offsets of the
      midpoint of the hard palate (A) and the base of the sella turcica (B), the
      horizontal convergents formed by the tangential line to the hard palate (C), and
      the line joining the center of the orbital orifice with the internal occipital
      protuberance (D). In the prospective cohort, good sensitivity (>98%) was attained
      when two or more parameters were used. Audit using Criterion B+D yielded
      compliance rates of 76.7%, a figure much closer to that of A+B+C+D (74.8%). From
      a practical viewpoint, Criterion B+D were most suitable for clinical use and
      could be simplified to the "3-6-12 rule" as a form of cursory assessment. Verbal
      instructions in the absence of stringent postural checks only ensured that ~75%
      of subjects achieved horizontal gaze. CONCLUSIONS: Fulfillment of Criterion B+D
      is sufficient to evaluate for horizontal gaze. Further criteria can be added to
      increase sensitivity. Verbal instructions alone yield high rates of inaccuracy
      when attempting to image patients in horizontal gaze. Apart from improving
      methods for obtaining radiographs, a radiological definition of horizontal gaze
      should be routinely applied for better evaluation of sagittal spinal alignment.

PMID- 29055742
TI  - Clinical evaluation of an innovative operative procedure in the treatment of the
      tethered cord syndrome.
AB  - BACKGROUND CONTEXT: The tethered cord syndrome (TCS) characterized by urination
      dysfunction has long been a worldwide clinical problem, of which clinical effects
      remains controversial. PURPOSE: The objective of this study was to evaluate the
      clinical effects of an innovative surgical method for the treatment of TCS. STUDY
      DESIGN: This is a retrospective clinical study. PATIENT SAMPLE: There were 15
      patients included in this study. OUTCOME MEASURES: The visual analog scale (VAS)
      and the Japanese Orthopaedic Association (JOA) scores were evaluated. The
      incidence of complications after surgery was also analyzed. MATERIALS AND
      METHODS: A total of 15 patients including 9 men and 6 women with TCS underwent
      homogeneous spinal-shortening axial decompression (HSAD) from September 2011 to
      February 2015. The average age at the time of surgery was 38.1+/-17.7 years. The
      average postoperative follow-up period was 21.5+/-7.5 months. The VAS and JOA
      scores were used to evaluate the clinical effects of the new operational
      procedure. In addition, the incidence of complications was also recorded and
      analyzed. RESULTS: The VAS scores decreased from 3.93+/-2.52 to 1.80+/-1.21 at
      the final follow-up after surgery with a significant statistical difference
      (p=.006). The JOA scores also significantly increased from 9.93+/-3.43 to 21.20+/
      4.18 at the final follow-up (p<.001). Fourteen cases (93.3%) with bladder
      dysfunction and 7 cases with sensory dysfunction of the lower limbs (87.5%) had a
      significant improvement postoperatively. Complications such as infection,
      pulmonary embolism, nerve injury, and broken rod were not observed during the
      follow-up period. CONCLUSIONS: The operation of HSAD was an effective and safe
      surgical method for TCS, which can achieve direct decompression of the tethered
      spinal cord.

PMID- 29055743
TI  - Am I Cut Out for This? Transitioning From Surgical Trainee to Attending.
AB  - OBJECTIVE: Progressing from trainee to attending surgeon is arguably one of the
      most significant transitions in a surgeon's career. Despite this, little is known
      about this critical period. The purpose of this study was to develop a framework
      for understanding the phenomenon of the transition from trainee to attending
      surgeon. DESIGN: A constructivist grounded theory methodology was used to explore
      the experience of new attending surgeons as they transition into practice. A
      purposeful sampling strategy was used to conduct 13 semistructured interviews
      with surgeons from various specialties. Data collection and analysis were
      performed simultaneously as part of the iterative process. Themes were identified
      and informed the development of the conceptual framework. SETTING: The setting
      included 4 separate Canadian urban, academic health centers. PARTICIPANTS: A
      total of 13 surgeons in their first 5 years of practice from 6 separate
      departments were included. RESULTS: Participants described 4 phases that marked
      their transition from trainee to attending surgeon. In the initial phase (getting
      undressed), participants shared vivid moments where they realized they no longer
      fit their trainee identity, but did not yet belong to the attending group. An
      intense phase of vulnerability and self-doubt (exposed and vulnerable), which was
      associated with building a new reputation and identity, followed. In the next
      phase (suiting up), surgeons began to project the image associated with their new
      role to others. With the passage of time and accumulation of successful cases,
      participants began to internalize their new identity in the final phase
      (tailoring the fit). CONCLUSIONS: The transition from trainee to attending
      surgeon is a critical time during which new surgeons experience an identity
      shift. The conceptual framework presented contributes to a deeper understanding
      of the experience of this transition in order to help new surgeons transition
      successfully into independent practice.

PMID- 29055744
TI  - The ACGME Case Log System May Not Accurately Represent Operative Experience Among
      General Surgery Interns.
AB  - OBJECTIVE: To assess if the Accreditation Council for Graduate Medical Education
      (ACGME) case log system accurately captures operative experience of our
      postgraduate year 1 (PGY-1) residents. DESIGN: ACGME case log information was
      retrospectively obtained for 5 cohorts of PGY-1 residents (2011-2015) and
      compared to the number of operative cases captured by an institutional automated
      operative case report system, Surgical Access Utility System (SAUS). SAUS
      automatically captures all surgical team members who are listed in the operative
      dictation for a given case, including interns. A paired t-test analysis was used
      to compare number of cases coded between the 2 systems. SETTING: Academic,
      tertiary care referral center with a large general surgery training program.
      PARTICIPANTS: PGY-1 general surgery trainees (interns) from the years 2011-2015.
      RESULTS: Forty-nine PGY-1 general surgery residents were identified over a 5-year
      period. Mean operative case volume per intern, per year, captured by the
      automated SAUS was 176.5 +/- 28.1 (SD) compared to 126.3 +/- 58.0 ACGME cases
      logged (mean difference = 50.2 cases, p < 0.001). CONCLUSIONS: ACGME case log
      data may not accurately reflect the actual operative experience of our PGY-1
      residents. If such data holds true for other general surgery training programs,
      the true impact of duty hour regulations on operative volume may be unclear when
      using the ACGME case log data. This current standard approach for using ACGME
      case logs as a representation of operative experience requires further scrutiny
      and potential revision to more accurately determine operative experience for
      accreditation purposes.

PMID- 29055746
TI  - Atrial fibrillation and arterial hypertension.
AB  - Atrial fibrillation (AF) and arterial hypertension frequently coexist, not only
      because arterial hypertension increases the incidence of new onset of atrial
      fibrillation, but also because those two entities share common risk factors and
      conditions that increase the incidence of both. Thus, in our daily clinical
      practice we will often have to manage and treat those patients. In order to
      assess and treat these patients, proper blood pressure (BP) measurement as well
      as detection of atrial fibrillation is mandatory. The use of oscillometric
      devices for home and ambulatory blood pressure measurements may accurately
      measure systolic but not diastolic blood pressure levels. Current guidelines
      suggest to palpate the pulse and perform an electrocardiogram (ECG) as well as a
      long-term ECG monitoring in order to detect AF. However there is evidence that:
      the use of oscillometric BP device with a specific algorithm for the detection of
      AF as well as the interrogation of a permanent pacemaker may further help
      physicians to reveal periods of AF. Finnaly, although guidelines suggests the use
      of specific drugs in order to treat arterial hypertension in AF patients, the
      main goal is BP control per se. In this review, we are going to summarize the
      diagnostic work up of these patients namely the proper arterial blood pressure
      measurement, the detection of atrial fibrillation as well as the treatment of
      these patients based on the latest data of the literature.

PMID- 29055745
TI  - Apigenin as neuroprotective agent: Of mice and men.
AB  - Neurodegenerative disorders (NDDs) such as Alzheimer's and Parkinson's diseases
      are the most common age-related pathologies that affect millions of people all
      over the world. To date, effective therapy for NDDs is not available and current
      approaches to disease management include neuroprotection strategy with a hope of
      maintaining and enhancing the function of survising neurons. Of course, such an
      approach by its own will not offer a cure but is likely to delay the disease
      progression by ameliorating the increase of neurotoxic agents such reactive
      oxygen species (ROS) as well as the associated inflammatory cascades. In this
      regard, natural products including flavonods that offer neuroprotection through
      multiple mechanisms have gained a lot of interest in recent years. In this
      communication, evidences from the various experimental models and clinical trials
      on the therapeutic potential of one promising flavonod, apigenin, is presented.
      Its chemistry, mechanism of action and potential benefits in the various examples
      of NDDs are discussed in the light of drug discovery aspects.

PMID- 29055747
TI  - Sex differences in prenatal stress effects on cocaine pursuit in rats.
AB  - Disruption of early-life ontogeny has severe and persistent consequences for the
      health of the developing organism. Both clinical and preclinical findings
      indicate that such interference can be caused by maternal stress during the
      gestation period (prenatal stress [PS]). In rats, PS facilitates the rewarding
      and neurochemical-stimulating effects of drugs, suggesting that PS may represent
      a risk factor for drug abuse in humans. Very little, however, is known about its
      effects in females, even though sex differences in drug susceptibility have been
      well documented in no PS (NPS) controls. Thus, we tested for independent effects
      and interactions between maternal restraint stress during the last week of
      gestation and sex on drug use with an extended regimen of drug self
      administration. Male and female rats were provided daily access to a large but
      controlled amount of cocaine for seven weeks. Drug pursuit during the final week
      was used to indicate susceptibility to developing an addiction-like phenotype,
      based on reports that drug use becomes increasingly compulsive-like after weeks
      of testing. Overall, females satisfied more addiction-like criteria than males,
      and the same was true for PS rats when compared to NPS controls. In addition, sex
      and PS interacted to disproportionately promote drug pursuit of females with a
      history of PS. These results indicate that sex differences in drug susceptibility
      persist with continued drug exposure, and that PS widens this difference by more
      severely affecting females. In all, PS may be a risk factor for drug addiction in
      humans, and to a greater extent in women vs. men.

PMID- 29055750
TI  - A massive overdose of potassium pills.

PMID- 29055749
TI  - Effect of social housing and oxytocin on the motivation to self-administer
      methamphetamine in female rats.
AB  - Social housing has been shown to attenuate the motivation for cocaine in female,
      but not male rats. Here we investigate the potential mechanisms mediating the
      effect of social housing on the response to methamphetamine (METH). Female rats
      were individually or socially (pair) housed. The dopamine (DA) response to an
      acute METH infusion (0.3mg/kg, i.v.) was investigated using in vivo microdialysis
      in the nucleus accumbens with or without oxytocin (OT; 0.3mg/kg, i.p.) 30min
      prior to METH. The effects of social housing and OT on self-administered METH
      (0.06mg/kg/inf) was investigated. The METH-induced DA response was higher in
      individually housed compared to socially-housed females. On the other hand,
      individually housed females had a significantly higher breaking point (BP) than
      socially-housed females. Two weeks of OT treatment reduced BP in both groups.
      Reinstatement to METH was more pronounced in isolates compared to socially-housed
      females. More of the socially-housed females had very low BP than did the
      individually housed females. OT was most effective in reducing BP in females with
      moderate to high BP, irrespective of housing conditions. These data show that
      social housing attenuates escalation of METH intake and reinstatement of METH
      seeking in female rats, and that chronic OT treatment can reduce motivation for
      METH.

PMID- 29055748
TI  - Sex- and dose-dependent abuse liability of repeated subanesthetic ketamine in
      rats.
AB  - RATIONALE: Subanesthetic ketamine (KET) elicits rapid, robust, but transient
      antidepressant effects. KET's antidepressant actions can be augmented and
      maintained for a longer duration when repeatedly delivered. However, KET is
      recreationally abused, raising long-term treatment safety concerns. Women are
      more likely than men to seek treatment for depression, escalate from casual to
      compulsive drug use, and are more sensitive to antidepressants. Similarly, female
      rodents are more sensitive than males to KET's rapid antidepressant-like
      behavioral effects; dose-response thresholds in these assays equal 2.5 and
      5.0mg/kg (i.p.), respectively. This suggests the utility of preclinical rodent
      models in optimizing sex-differential KET therapy protocols and minimizing
      adverse drug reactions. OBJECTIVES: Here, we assessed behavioral and biochemical
      correlates of abuse liability following six serial KET treatments on alternating
      days at three subanesthetic, antidepressant-like doses (2.5, 5.0, or 10mg/kg,
      i.p.) in adult male and female rats. A potential role for DeltaFosB-mediated
      transcription in the nucleus accumbens is outlined in the context of KET-mediated
      locomotor sensitization. RESULTS: Antidepressant-like threshold doses (2.5,
      5.0mg/kg KET) failed to evoke a conditioned place preference in all animals, but
      only males positively responded to a higher dose (10mg/kg). Behavioral
      sensitization to 5.0 or 10mg/kg KET's locomotor-activating effects was
      established in both sexes, and females' sensitized response to 5.0mg/kg was
      greater than males'. KET-induced hyperlocomotion positively correlated with
      DeltaFosB protein expression in the nucleus accumbens. rAAV-DeltaJunD inhibition
      of DeltaFosB-mediated transcription in the accumbens failed to block locomotor
      sensitization to 10mg/kg KET. CONCLUSIONS: These data suggest that in rats, six
      alternating-day treatments with 2.5mg/kg KET do not induce apparent behavioral
      signatures of abuse liability despite accumulation of DeltaFosB protein in the
      accumbens. Additionally, females are more sensitive than males to KET's locomotor
      stimulant properties, both acutely and after repeated treatments. More studies
      are needed to determine brain regions and neural mechanisms responsible for KET
      induced behavioral adaptations and to extrapolate these data to inform sex
      dependent strategies for long-term KET therapy protocols for depression.

PMID- 29055751
TI  - Post-cardiac arrest syndrome: pathological processes, biomarkers and vasopressor
      support, and potential therapeutic targets.

PMID- 29055752
TI  - Relationship between protein molecular structural makeup and metabolizable
      protein supply to dairy cattle from new cool-season forage corn cultivars.
AB  - Protein solubility, ruminal degradation and intestinal digestibility are strongly
      related to their inherent molecular makeup. This study was designed to
      quantitatively evaluate protein digestion in the rumen and intestine of dairy
      cattle, and estimate the content of truly metabolizable protein (MP) in newly
      developed cool-season forage corn cultivars. The second objective was to quantify
      protein inherent molecular structural characteristics using advance molecular
      spectroscopic technique (FT/IR-ATR) and correlate it to protein metabolic
      characteristics. Six new cool-season corn cultivars, including 3 Pioneer (PNR)
      and 3 Hyland (HL), coded as PNR-7443R, PNR-P7213R, PNR-7535R, HL-SR06, HL-SR22,
      HL-BAXXOS-RR, were evaluated in the present study. The metabolic characteristics,
      MP supply to dairy cattle, and energy synchronization properties were modeled by
      two protein evaluation models, namely, the Dutch DVE/OEB system and the NRC-2001
      model. Both models estimated significant (P<0.05) differences in contents of
      microbial protein (MCP) synthesis and truly absorbable rumen undegraded protein
      (ARUP) among the cultivars. The NRC-2001 model estimated significant (P<0.05)
      differences in MP content and degraded protein balance (DPB) among the cultivars.
      The contents MCP, ARUP and MP were higher (P<0.05) for cultivar HL-SR06,
      resulting in the lowest (P<0.05) DPB. However, none of the cultivars reached the
      optimal target hourly effective degradability ratio [25gNg/kg organic matter
      (OM)], demonstrating N deficiency in the rumen. There were non-significant
      differences among the cultivars in molecular-spectral intensities of protein. The
      amide I/II ratio had a significant correlation with ARUP (r=-0.469; P<0.001) and
      absorbable endogenous protein (AECPNRC) (P<0.001; r=0.612). Similarly, amide-II
      area had a weak but significant correlation (r=0.299; P<0.001) with RUP and ARUP,
      and with AECPNRC (P<0.001; r=0.411). Except total digestible nutrients and
      AECPNRC, the amide-I area did not show significant correlations with DVE/OEB and
      NRC predicted protein fractions. This study shows that molecular spectroscopy can
      be potentially used as a rapid tool to quantify protein molecular makeup and
      screen the protein nutritive value of forage corn.

PMID- 29055753
TI  - Dielectric spectroscopy study of water hyacinth collected from different media.
AB  - X-ray fluorescence (XRF) study has been shown that the water hyacinth plant is an
      effective tool for the removals of heavy metals (As, Ba, Cr, Cu, Ni, Pb, Rb, Sr,
      Zn and Zr) and metal oxides (SiO2, K2O, CaO, Al2O3, Fe2O3, MgO, Na2O, MnO, P2O5,
      SO3 and TiO2) from agriculture (media 1) and agriculture wastewaters drainage
      polluted with municipal wastewater (media 2). As a general description, the heavy
      metals and metal oxides were found at higher levels in the plant collected from
      media 1 than those in the plant collected from media 2. Similarly, these
      pollutants were found at higher levels in the plant roots than those in the plant
      shoots. The dielectric properties were investigated for the plant samples before
      (control) and after treating by microwave heating power. They were found at
      higher values in the control roots than those in the control shoots. Furthermore,
      the properties were found at relatively higher values in the control roots
      collected from media 1 (epsilon'=13 at 103Hz) than those in the control roots
      collected from media 2 (epsilon'=9 at 103Hz). The electrical conductivity of the
      microwave treated samples remarkably increased due to appearance of OH group
      through which the plant interacts with heavy metals. Accordingly, the pollutants
      removing ability could be enhanced upon treating the plant by microwave heating
      power. The plant-pollutant mixture behaves like highly conductive disordered
      polymers. The conductivity and dielectric properties of all plant samples are
      dominated by the media and concentration of pollutants.

PMID- 29055754
TI  - A turn-on supramolecular fluorescent probe for sensing benzimidazole fungicides
      and its application in living cell imaging.
AB  - A cucurbit[8]uril-based turn-on supramolecular fluorescent probe between
      cucurbit[8]uril (Q[8]) and pyronine Y (PyY) (designated 2PyY@Q[8]) in acidic
      aqueous solution showed a remarkable fluorescence 'turn-on' response to
      benzimidazole fungicides such as thiabendazole, fuberidazole and carbendazim. The
      2PyY@Q[8] fluorescent probe can be used to detect benzimidazole fungicides with
      high sensitivity and selectivity with a detection limit of ~10-8mol/L. A good
      linear relationship of emission intensity at ~580nm for benzimidazole fungicides
      at concentrations of 0.4-5.0MUmol/L was observed. The proposed sensing mechanism
      was investigated using 1H NMR spectroscopy combined with density functional
      theory calculations at the B3LYP/6-31G(d) level. The cell imaging study showed
      that the 2PyY@Q[8] complex could be used to image benzimidazole fungicide in
      prostate cancer (PC3) cells, which may help to elucidate relevant biological
      processes at the molecular level.

PMID- 29055755
TI  - Spectroscopic investigation on structure and pH dependent Cocrystal formation
      between gamma-aminobutyric acid and benzoic acid.
AB  - Vibrational spectroscopic methods, including terahertz absorption and Raman
      scattering spectroscopy, were utilized for the characterization and analysis of
      gamma-aminobutyric acid (GABA), benzoic acid (BA), and the corresponding GABA-BA
      cocrystal formation under various pH values of aqueous solution. Vibrational
      spectroscopic results demonstrated that the solvent GABA-BA cocrystal, similar as
      grinding counterpart, possessed unique characteristic features compared with that
      of starting parent compounds. The change of vibrational modes for GABA-BA
      cocrystal comparing with starting components indicates there is strong inter
      molecular interaction between GABA and BA molecules during its cocrystallization
      process. Formation of GABA-BA cocrystal under slow solvent evaporation is
      impacted by the pH value of aqueous solution. Vibrational spectra indicate that
      the GABA-BA cocrystal could be stably formed with the solvent condition of
      2.00<=pH<=7.00. In contrast, such cocrystallization did not occur and the
      cocrystal would dissociate into its parent components when the pH value of
      solvent is lower than 2.00. This study provides experimental benchmark to
      discriminate and identify the structure of cocrystal and also pH-dependent
      cocrystallization effect with vibrational spectroscopic techniques in solid-state
      pharmaceutical fields.

PMID- 29055756
TI  - DFT calculations for anharmonic force field and spectroscopic constants of YC2
      and its 13C isotopologues.
AB  - The construction of the complete third and the semi-diagonal quartic force fields
      including the anharmonicity of the ground state (X~2A1) for yttrium dicarbide
      (YC2) is carried out employing the vibrational second-order perturbation theory
      (VPT2) in combination with the density functional theory (DFT). The equilibrium
      geometries optimization, anharmonic force field and vibrational spectroscopic
      constants of YC2 are calculated by B3LYP, B3PW91 and B3P86 methods. Aug-cc-pVnZ
      (n=D, T, Q) and cc-pVnZ-PP (n=D, T, Q) basis sets are chosen for C and Y atoms,
      respectively. The calculated geometry parameters of YC2 agree well with the
      corresponding experimental and previous theoretical results. The bonding
      characters of YC2 or CC are discussed. Based on the optimized equilibrium
      geometries, the spectroscopic constants and anharmonic force field of YC2 are
      calculated. Comparing with the spectroscopic constants of YC2 derived from the
      experiment, the calculated results show that the B3PW91 and B3P86 methods are
      superior to B3LYP for YC2. The Coriolis coupling constants, cubic and quartic
      force constants of YC2 are reasonably predicted. Besides, the spectroscopic
      constants and anharmonic force field of Y13C2 (X~2A1) and Y13CC (X~2A') are
      calculated for the first time, which are expected to guide the high resolution
      experimental work for YC2 and its 13C isotopologues.

PMID- 29055757
TI  - Strategies for Managing Functional Tricuspid Regurgitation in Adults With a
      Secundum Atrial Septal Defect.

PMID- 29055758
TI  - Left Atrial Appendage Occlusion in the Presence of Thrombus With a LAmbre Device.

PMID- 29055759
TI  - Chronic Total Occlusion Trials: A Step in the Right Direction.

PMID- 29055760
TI  - Giant Coronary Artery Pseudoaneurysm Formed After Septal Artery Perforation
      During Retrograde Percutaneous Coronary Intervention: A Conservative Strategy
      With Serial Cardiac Computed Tomographic Imaging.

PMID- 29055761
TI  - Functional Tricuspid Regurgitation After Transcatheter Closure of Atrial Septal
      Defect in Adult Patients: Long-Term Follow-Up.
AB  - OBJECTIVES: This study aimed to assess the fate of tricuspid regurgitation (TR)
      after transcatheter atrial septal defect (ASD) closure. BACKGROUND: Although TR
      frequently occurs in patients with ASD, the change in TR during long-term follow
      up after ASD closure remains unknown. METHODS: A total of 419 adult patients who
      underwent transcatheter ASD closure were enrolled. TR severity was graded by TR
      jet area on echocardiography. RESULTS: At baseline, 113 patients had
      severe/moderate TR and 306 patients had mild TR. Among the 113 patients with
      severe/moderate TR, the TR jet area significantly decreased during a median
      follow-up of 30 months after the procedure; this decrease was related to the
      improvement in right ventricular morphology. The severity of TR decreased to mild
      in 79 (70%) patients. Persistent TR, defined as severe or moderate TR after the
      procedure, was independently associated with the prevalence of permanent atrial
      fibrillation. Regarding clinical outcomes, 7 patients with severe/moderate TR and
      2 with mild TR were hospitalized because of heart failure. Patients with
      severe/moderate TR had the worse event-free survival rate than those with mild
      TR, but more than 90% of them had no cardiovascular events. New York Heart
      Association functional class and plasma B-type natriuretic peptide levels
      improved in patients with severe/moderate TR, similar to those with mild TR.
      CONCLUSIONS: Significant TR decreased during the long-term follow-up period after
      transcatheter ASD closure. Heart failure symptoms improved in patients with
      severe/moderate TR. Our findings suggest that transcatheter closure alone can be
      valuable in patients with ASD complicated with TR.

PMID- 29055763
TI  - Lower Limb Bone Metastasis Discovered After Femoropopliteal Artery Stenting.

PMID- 29055762
TI  - Percutaneous Coronary Intervention of Chronic Total Occlusions in Patients With
      Low Left Ventricular Ejection Fraction.
AB  - OBJECTIVES: The study sought to assess the outcome of percutaneous coronary
      intervention (PCI) of chronic total occlusions (CTOs) in patients with low left
      ventricular ejection fraction (LVEF) (<=35%). BACKGROUND: Data regarding the
      outcome of PCI in patients with low LVEF affected by CTO are scarcely reported.
      METHODS: The authors performed a prospective longitudinal multicenter study
      including consecutive patients undergoing elective PCI of CTOs. Patients were
      subdivided into 3 groups: group 1 (LVEF >=50%), group 2 (LVEF 35% to 50%), and
      group 3 (LVEF <=35%). RESULTS: A total of 839 patients (mean 64.6 +/- 10.5 years
      of age, 87.7% men) underwent CTO PCI attempts. Baseline LVEF <=35% was present in
      72 (8.6%) patients. The angiographic success was high (overall 93.6%) and similar
      among the 3 groups (93.5% vs. 94.4% vs. 91.7%, respectively; all p = NS). In
      group 3, no periprocedural complications of CTO PCI were observed. Mean clinical
      follow-up of 16.3 +/- 8.2 months duration was available in 781 (93.1%) patients
      including those with LVEF <=35%. At 2 years, major cardiac and cerebrovascular
      events (MACCE) free survival was similar in the 3 groups (86% vs. 82.8% vs.
      75.2%; all p = NS). In patients with LVEF <=35%, LVEF improved significantly in
      the presence of a successful CTO PCI from 29.1 +/- 3.4% to 41.6 +/- 7.9% (p <
      0.001). CONCLUSIONS: In CTO patients with low LVEF, PCI could represent a safe
      and effective revascularization strategy achieving good midterm outcome and LVEF
      improvement.

PMID- 29055765
TI  - Percutaneous Treatment of Chronic Total Coronary Occlusions: The Light That Came
      From Japan.

PMID- 29055764
TI  - Outcomes of Percutaneous Coronary Interventions for Chronic Total Occlusion
      Performed by Highly Experienced Japanese Specialists: The First Report From the
      Japanese CTO-PCI Expert Registry.
AB  - OBJECTIVES: This report describes the registry and presents an initial analysis
      of outcomes for the different PCI approaches taken by the specialists.
      BACKGROUND: Strategies for percutaneous coronary intervention (PCI) for chronic
      total occlusion (CTO) are complex. The Japanese Board of CTO Interventional
      Specialists has developed a prospective, nonrandomized registry of patients
      undergoing CTO-PCIs performed by 41 highly experienced Japanese specialists.
      METHODS: Over the study period of January 2014 to December 2015, the registry
      included 2,846 consecutive CTO-PCI cases undertaken in Japan. The authors
      compared clinical outcomes between the different PCI approaches, following the
      intention-to-treat principle. RESULTS: The overall technical success rate of the
      procedures was 89.9%. The specialists frequently chose a retrograde approach as
      the primary CTO-PCI strategy (in 27.8% of cases). The technical success rate of
      the primary antegrade approach was significantly better than that of the primary
      retrograde approach (91.0% vs. 87.3%; p < 0.0001). The technical success rate
      decreased to 78.0% with the rescue retrograde approach. Parallel guidewire
      crossing and intravascular ultrasound-guided wire crossing were performed after
      guidewire escalation during antegrade CTO-PCI with a high technical success rate
      (75.0% to 88.9%). Severe lesion calcification was a strong predictor of failed
      CTO-PCI. CONCLUSIONS: CTO-PCI performed by highly experienced specialists
      achieved a high technical success rate.

PMID- 29055766
TI  - Hypoxemia Due to Patent Foramen Ovale in the Setting of New Right
      Hemidiaphragmatic Paralysis.

PMID- 29055767
TI  - Long-Term Outcomes With Transcatheter Aortic Valve Replacement in Women Compared
      With Men: Evidence From a Meta-Analysis.
AB  - OBJECTIVES: This study sought to examine long-term outcomes with transcatheter
      aortic valve replacement (TAVR) in women versus men. BACKGROUND: TAVR is commonly
      performed in women. Previous studies have shown conflicting results with respect
      to sex differences in outcomes with TAVR. In addition, short-term outcomes have
      primarily been reported. METHODS: Electronic search was performed until March
      2017 for studies reporting outcomes with TAVR in women versus men. Random effects
      DerSimonian-Laird risk ratios were calculated. Outcomes included all-cause
      mortality and major cardiovascular events at short- (30 days) and long-term (>1
      year) follow-up. RESULTS: Seventeen studies (8 TAVR registries; 47,188 patients;
      49.4% women) were analyzed. Women were older but exhibited fewer comorbidities.
      At 30 days, women had more bleeding (p < 0.001), vascular complications (p <
      0.001), and stroke/transient ischemic attack (p = 0.02), without difference in
      all-cause (p = 0.19) or cardiovascular mortality (p = 0.91) compared with men.
      However, female sex was associated with lower all-cause mortality at 1 year (risk
      ratio: 0.85; 95% confidence interval: 0.79 to 0.91; p < 0.001), and longest
      available follow-up (mean 3.28 +/- 1.04 years; risk ratio: 0.86; 95% confidence
      interval: 0.81 to 0.92; p < 0.001), potentially caused by less moderate/severe
      aortic insufficiency (p = 0.001), and lower cardiovascular mortality (p = 0.009).
      The female survival advantage remained consistent across multiple secondary
      analyses. The risk of stroke, moderate/severe aortic insufficiency, and all-cause
      mortality seemed to vary based on the type of valve used; however, without
      significant subgroup interactions. CONCLUSIONS: Despite a higher upfront risk of
      complications, women derive a better long-term survival after TAVR compared with
      men.

PMID- 29055768
TI  - Acute Obstructive Thrombosis of Sapien 3 Valve After Valve-in-Valve Transcatheter
      Aortic Valve Replacement for Degenerated Mosaic 21 Valve.

PMID- 29055769
TI  - Retrograde Variant Artery Approach for Infrapopliteal Chronic Total Occlusion
      Intervention.

PMID- 29055771
TI  - Erratum to "Systematic literature review of health-related quality of life in
      locally-advanced non-small cell lung cancer: Has it yet become state-of-the-art?"
      [Crit. Rev. Oncol. Hematol., 119 (November) (2017) 40-49].

PMID- 29055770
TI  - Implementation of a multidisciplinary, team-based model to treat chronic
      hepatitis C in the primary care setting: Lessons learned.
AB  - Hepatitis C virus (HCV) is the most common blood-borne virus in the U.S., and its
      incidence continues to rise. With approval of direct-acting antiviral
      medications, treatment for Chronic Hepatitis C (CHC) has become highly
      efficacious with a minimal side effect profile. Primary care physicians are well
      positioned to address this increased demand, yet most do not feel comfortable
      treating CHC. In this case report, we describe implementation of a
      multidisciplinary team-based approach for treating CHC at multiple primary care
      sites across a large safety net health system. We focus on the evolving nature of
      implementation of our model through iterative Plan-Do-Study-Act (PDSA) cycles,
      highlighting the importance of developing an interdependent, multidisciplinary
      team, providing training, and ongoing support of Primary Care Hepatitis C
      Specialists, responding to the evolving nature of CHC treatment and policies, and
      ensuring high quality treatment. This process allowed us to continually grow and
      adapt our approach to make it feasible and successful. We share our "lessons"
      learned for others looking to bring CHC treatment, and potentially other
      specialty-based treatment, into the primary care setting.

PMID- 29055772
TI  - Exploring the relationship between appearance-contingent self-worth and self
      esteem: The roles of self-objectification and appearance anxiety.
AB  - Previous work has shown that both an appearance-contingent self-worth (i.e.,
      staking one's overall self-evaluation on one's physical appearance) and self
      objectification are associated with higher appearance anxiety and lower self
      esteem among women. Although prior evidence separately links both appearance
      contingent self-worth and self-objectification to these negative outcomes, no
      work has examined the mediating processes that may underlie this relationship.
      With the current project, we examined the relationship between appearance
      contingent self-worth and self-objectification, and the degree to which this
      relationship is associated with higher appearance anxiety and lower overall self
      esteem. We hypothesized that appearance-contingent self-worth would be positively
      associated with self-objectification; in turn, we expected self-objectification
      to be related to higher appearance anxiety, and ultimately, lower self-esteem.
      Across two studies, one cross-sectional (N=208) and one short-term longitudinal
      (N=191), we found compelling support for this hypothesis. These findings have
      practical and theoretical significance for both the self-objectification and
      contingent self-worth literatures.

PMID- 29055773
TI  - The relationship between Facebook and Instagram appearance-focused activities and
      body image concerns in young women.
AB  - The present study aimed to identify the specific social networking sites (SNS)
      features that relate to body image concerns in young women. A total of 259 women
      aged 18-29years completed questionnaire measures of SNS use (Facebook and
      Instagram) and body image concerns. It was found that appearance-focused SNS use,
      rather than overall SNS use, was related to body image concerns in young women.
      Specifically, greater engagement in photo activities on Facebook, but not general
      Facebook use, was associated with greater thin-ideal internalisation and body
      surveillance. Similarly, following appearance-focused accounts on Instagram was
      associated with thin-ideal internalisation, body surveillance, and drive for
      thinness, whereas following appearance-neutral accounts was not associated with
      any body image outcomes. Implications for future SNS research, as well as for
      body image and disordered eating interventions for young women, are discussed.

PMID- 29055774
TI  - Functional nanoparticles exploit the bile acid pathway to overcome multiple
      barriers of the intestinal epithelium for oral insulin delivery.
AB  - Oral absorption of protein/peptide-loaded nanoparticles is often limited by
      multiple barriers of the intestinal epithelium. In addition to mucus
      translocation and apical endocytosis, highly efficient transepithelial absorption
      of nanoparticles requires successful intracellular trafficking, especially to
      avoid lysosomal degradation, and basolateral release. Here, the functional
      material, deoxycholic acid-conjugated chitosan, is synthesized and loaded with
      the model protein drug insulin into deoxycholic acid-modified nanoparticles
      (DNPs). The DNPs designed in this study are demonstrated to overcome multiple
      barriers of the intestinal epithelium by exploiting the bile acid pathway. In
      Caco-2 cell monolayers, DNPs are internalized via apical sodium-dependent bile
      acid transporter (ASBT)-mediated endocytosis. Interestingly, insulin degradation
      in the epithelium is significantly prevented due to endolysosomal escape of DNPs.
      Additionally, DNPs can interact with a cytosolic ileal bile acid-binding protein
      that facilitates the intracellular trafficking and basolateral release of
      insulin. In rats, intravital two-photon microscopy also reveals that the
      transport of DNPs into the intestinal villi is mediated by ASBT. Further
      pharmacokinetic studies disclose an oral bioavailability of 15.9% in type I
      diabetic rats after loading freeze-dried DNPs into enteric-coated capsules. Thus,
      deoxycholic acid-modified chitosan nanoparticles can overcome multiple barriers
      of the intestinal epithelium for oral delivery of insulin.

PMID- 29055775
TI  - Bio-artificial tongue with tongue extracellular matrix and primary taste cells.
AB  - Artificial taste devices for tastant sensing and taste information
      standardization are attracting increasing attention with the exponential growth
      of the food and beverage industries. Despite recent developments in artificial
      taste sensors incorporating polymers, lipid membranes, and synthetic vesicles,
      current devices have limited functionality and sensitivity, and are complex to
      manufacture. Moreover, such synthetic systems cannot simulate the taste signal
      transmissions that are critical for complicated taste perception. The current
      document describes a primary taste cell-based artificial tongue that can mimic
      taste sensing. To maintain viable and functional taste cells required for in
      vitro tastant sensing, a tongue extracellular matrix (TEM) prepared by
      decellularization of tongue tissue was applied to two- and three-dimensional
      taste cell cultures. The TEM-based system recreates the tongue's microenvironment
      and significantly improves the functionality of taste cells for sensing tastant
      molecules by enhancing cellular adhesion and gustatory gene expression compared
      with conventional collagen-based systems. The TEM-based platform simulates signal
      transmission from tastant-treated taste cells to adjacent neuronal cells, which
      was impossible with previous artificial taste sensors. The artificial tongue
      device may provide highly efficient, functional sensors for tastant detection and
      in vitro organ models that mimic the tongue allowing elucidation of the
      mechanisms of taste.

PMID- 29055776
TI  - Effects of temperature, genetic variation and species competition on the
      sensitivity of algae populations to the antibiotic enrofloxacin.
AB  - Primary producers are amongst the most sensitive organisms to antibiotic
      pollution in aquatic ecosystems. To date, there is little information on how
      different environmental conditions may affect their sensitivity to antibiotics.
      In this study we assessed how temperature, genetic variation and species
      competition may affect the sensitivity of the cyanobacterium Microcystis
      aeruginosa and the green-algae Scenedesmus obliquus to the antibiotic
      enrofloxacin. First, we performed single-species tests to assess the toxicity of
      enrofloxacin under different temperature conditions (20 degrees C and 30 degrees
      C) and to assess the sensitivity of different species strains using a standard
      temperature (20 degrees C). Next, we investigated how enrofloxacin contamination
      may affect the competition between M. aeruginosa and S. obliquus. A competition
      experiment was performed following a full factorial design with different
      competition treatments, defined as density ratios (i.e. initial bio-volume of
      25/75%, 10/90% and 1/99% of S. obliquus/M. aeruginosa, respectively), one 100% S.
      obliquus treatment and one 100% M. aeruginosa treatment, and four different
      enrofloxacin concentrations (i.e. control, 0.01, 0.05 and 0.10mg/L). Growth
      inhibition based on cell number, bio-volume, chlorophyll-a concentration as well
      as photosynthetic activity were used as evaluation endpoints in the single
      species tests, while growth inhibition based on measured chlorophyll-a was
      primarily used in the competition experiment. M. aeruginosa photosynthetic
      activity was found to be the most sensitive endpoint to enrofloxacin (EC50-72h
      =0.02mg/L), followed by growth inhibition based on cell number. S. obliquus was
      found to be slightly more sensitive at 20 degrees C than at 30 degrees C (EC50
      72h cell number growth inhibition of 38 and 41mg/L, respectively), whereas an
      opposite trend was observed for M. aeruginosa (0.047 and 0.037mg/L,
      respectively). Differences in EC50-72h values between algal strains of the same
      species were within a factor of two. The competition experiment showed that M.
      aeruginosa growth can be significantly reduced in the presence of S. obliquus at
      a density ratio of 75/25% M. aeruginosa/S. obliquus, showing a higher
      susceptibility to enrofloxacin than in the single-species test. The results of
      this study confirm the high sensitivity of cyanobacteria to antibiotics and show
      that temperature and inter-strain genetic variation may have a limited influence
      on their response to them. The results of the competition experiment suggest that
      the structure of primary producer communities can be affected, at least
      temporarily, at antibiotic concentrations close to those that have been measured
      in the environment.

PMID- 29055777
TI  - Characterization of classical major histocompatibility complex (MHC) class II
      genes in northern pig-tailed macaques (Macaca leonina).
AB  - The northern pig-tailed macaque (Macaca leonina) has been identified as an
      independent species from the pig-tailed macaque group. The species is a promising
      animal model for HIV/AIDS pathogenesis and vaccine studies due to susceptibility
      to HIV-1. However, the major histocompatibility complex (MHC) genetics in
      northern pig-tailed macaques remains poorly understood. We have previously
      studied the MHC class I genes in northern pig-tailed macaques and identified 39
      novel alleles. Here, we describe the MHC class II alleles in all six classical
      loci (DPA, DPB, DQA, DQB, DRA, and DRB) from northern pig-tailed macaques using a
      sequence-based typing method for the first time. A total of 60 MHC-II alleles
      were identified of which 27 were shared by other macaque species. Additionally,
      northern pig-tailed macaques expressed a single DRA and multiple DRB genes
      similar to the expression in humans and other macaque species. Polymorphism and
      positive selection were detected, and phylogenetic analysis suggested the
      presence of a common ancestor in human and northern pig-tailed macaque MHC class
      II allelic lineages at the DQA, DQB, and DRB loci. The characterization of full
      length MHC class II alleles in this study significantly improves understanding of
      the immunogenetics of northern pig-tailed macaques and provides the groundwork
      for future animal model studies.

PMID- 29055778
TI  - Structural Basis for the Persistence of Homing Endonucleases in Transcription
      Factor IIB Inteins.
AB  - Inteins are mobile genetic elements that are spliced out of proteins after
      translation. Some inteins contain a homing endonuclease (HEN) responsible for
      their propagation. Hedgehog/INTein (HINT) domains catalyzing protein splicing and
      their nested HEN domains are thought to be functionally independent because of
      the existence of functional mini-inteins without HEN domains. Despite the lack of
      obvious mutualism between HEN and HINT domains, HEN domains are persistently
      found at one specific site in inteins, indicating their potential functional role
      in protein splicing. Here we report crystal structures of inactive and active
      mini-inteins derived from inteins residing in the transcription factor IIB of
      Methanococcus jannaschii and Methanocaldococcus vulcanius, revealing a novel
      modified HINT fold that might provide new insights into the mutualism between the
      HEN and HINT domains. We propose an evolutionary model of inteins and a
      functional role of HEN domains in inteins.

PMID- 29055779
TI  - Ubiquitome Analysis Reveals PCNA-Associated Factor 15 (PAF15) as a Specific
      Ubiquitination Target of UHRF1 in Embryonic Stem Cells.
AB  - Ubiquitination is a multifunctional posttranslational modification controlling
      the activity, subcellular localization and stability of proteins. The E3
      ubiquitin ligase ubiquitin-like PHD and RING finger domain-containing protein 1
      (UHRF1) is an essential epigenetic factor that recognizes repressive histone
      marks as well as hemi-methylated DNA and recruits DNA methyltransferase 1. To
      explore enzymatic functions of UHRF1 beyond epigenetic regulation, we conducted a
      comprehensive screen in mouse embryonic stem cells to identify novel
      ubiquitination targets of UHRF1 and its paralogue UHRF2. We found differentially
      ubiquitinated peptides associated with a variety of biological processes such as
      transcriptional regulation and DNA damage response. Most prominently, we
      identified PCNA-associated factor 15 (PAF15; also known as Pclaf, Ns5atp9,
      KIAA0101 and OEATC-1) as a specific ubiquitination target of UHRF1. Although the
      function of PAF15 ubiquitination in translesion DNA synthesis is well
      characterized, the respective E3 ligase had been unknown. We could show that
      UHRF1 ubiquitinates PAF15 at Lys 15 and Lys 24 and promotes its binding to PCNA
      during late S-phase. In summary, we identified novel ubiquitination targets that
      link UHRF1 to transcriptional regulation and DNA damage response.

PMID- 29055780
TI  - Pregnancy outcomes associated with extended use of the 52-mg 20 MUg/day
      levonorgestrel-releasing intrauterine system beyond 60 months: A chart review of
      776 women in Brazil.
AB  - OBJECTIVE: To assess the contraceptive performance of the 52-mg 20 MUg/day
      levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena; Bayer Oy, Turku,
      Finland) among women who maintain the same device without changes after 60
      months. STUDY DESIGN: This is a chart review study in which we assessed the
      charts of 766 women who continue the same LNG-IUS for contraception beyond 60
      months. The women were evaluated at the Family Planning clinic, University of
      Campinas Medical School, Campinas, SP, Brazil, from November 1990 to March 2011.
      We obtained sociodemographic data, duration of use, continuation and
      discontinuation rates and reasons, bleeding pattern at the recorded last visit.
      The statistical analysis was performed using Kaplan-Meier analysis. RESULTS: A
      total of 776 charts were identified of women who used the LNG-IUS beyond 60
      months. The mean age (+/-S.E.M.) at LNG-IUS placement was 32.0+/-0.2 years
      (ranged 15 to 44 years; median was 32 years). The distribution of number of
      pregnancies was 0-1 (45%); 2-4 (54.1%) and>=5 (0.9%). The median length of the
      LNG-IUS' use was 73 months after placement (ranged 61-184 months). Zero
      pregnancies were reported and the main reasons for discontinuation were
      expiration of approved effective lifespan, menopause and planning pregnancy. The
      cumulative women-years (W-Y) of exposure were 967 and 1403 up to seven and 15
      years, respectively. The main bleeding pattern reported by the women was
      amenorrhea. CONCLUSIONS: The 52-mg 20 MUg/day LNG-IUD (Mirena) showed continue
      contraceptive efficacy beyond 5 years of use with no pregnancies detected over
      967 and 1403 W-Y up to seven and 15 years after placement. IMPLICATIONS
      STATEMENT: The 52-mg 20 MUg/day LNG-IUD presented a very high contraceptive
      efficacy beyond the first 5 years of lifetime labeled. Increasing data support
      that efficacy beyond 5 years of use, and new data suggested efficacy as long as
      15 years. Healthcare professionals, policy makers and stakeholders could take
      advantage of the present information to decide to maintain the same device at
      least up to seven years. Furthermore, amenorrhea could be a good indicator of
      contraceptive effect.

PMID- 29055781
TI  - Induced abortion among women veterans: data from the ECUUN study.
AB  - OBJECTIVE: We compared rates of induced abortion among women veterans receiving
      Veterans Affairs (VA) healthcare to rates in the general US population, as
      current policy prohibits VA provision of abortion counseling or services even
      when pregnancy endangers a veteran's life. METHODS: We analyzed data from 2298
      women veterans younger than 45 years who completed a telephone-based, cross
      sectional survey of randomly sampled English-speaking women from across the
      United States who had received VA healthcare. We compared lifetime, last-5-year
      and last-year rates of unintended pregnancy and abortion among participants to
      age-matched data from the National Survey of Family Growth. As few abortions were
      reported in the last year, we used multivariable logistic regression to examine
      associations between abortion in the last 5 years and age, race/ethnicity,
      income, education, religion, marital status, parity, geography, deployment
      history, housing instability, and past medical and mental health among VA
      patients. RESULTS: Women veterans were more likely than matched US women to
      report ever having an abortion [17.7%, 95% confidence interval (CI): 16.1%-19.3%
      vs. 15.2% of US women]. In the last 5 years, unintended pregnancy and abortion
      were reported by veterans at rates similar to US women. In multivariable models,
      VA patients were more likely to report abortion in the last 5 years if their
      annual income was less than $40,000 (adjusted odds ratio (OR) 2.95, 95% CI 1.30
      6.70), they had experienced homelessness or housing instability (adjusted OR
      1.91, 95% CI 1.01-3.62), they were single (adj. OR 2.46, 95% CI 1.23-4.91) and/or
      they had given birth (adjusted OR 2.29, 95% CI 1.19-4.40). CONCLUSION: Women
      veterans face unintended pregnancy and seek abortion as often as the larger US
      population. IMPLICATIONS: The Veterans Health Care Act, which prohibits provision
      of abortion services, increases vulnerable veterans' out-of-pocket healthcare
      costs and limits veterans' reproductive freedom.

PMID- 29055782
TI  - Interest in multipurpose prevention technologies to prevent HIV/STIs and
      unintended pregnancy among young women in the United States.
AB  - OBJECTIVE: High rates of sexually transmitted infections (STIs) and unintended
      pregnancy suggest a role for multipurpose prevention technologies (MPTs) designed
      to combine contraception and infection prophylaxis into one unified method. This
      study aims to determine factors associated with interest in MPTs among US women.
      STUDY DESIGN: We administered a national cross-sectional survey via MTurk.
      Eligibility criteria included female gender, age 18-29 years, residence in the
      USA, and sexual activity with a male partner in the past three months. In total,
      835 surveys were suitable for analysis. Bivariable and multivariable logistic
      regressions were performed to determine factors associated with interest in MPTs.
      RESULTS: Eighty-three percent of women were interested in MPTs. Factors
      associated with interest included oral sex in the past three months (aOR 1.87,
      95% CI 1.07, 3.53), recent use of oral contraceptive pills (OCPs; aOR 1.78, 95%
      CI 1.08, 2.93), HIV test within one year (aOR 2.10, 95% CI 1.29, 3.40), and
      increased STI worry score (aOR 1.98, 95% CI 1.36, 2.86). No use of contraception
      in the past three months was associated with decreased interest in MPTs (aOR
      0.31, 95% CI 0.17, 0.58). HIV risk factors including race were not associated
      with MPT interest. CONCLUSION: Our data show that young, sexually active, US
      women are interested in MPTs. Women who used contraception, specifically OCPs, or
      evidenced concern for infection were most likely to be interested in such a
      product. Women reporting unsafe sexual habits were less likely to be interested,
      highlighting the importance of HIV/STI prevention education. IMPLICATIONS: Women
      in the USA are interested in multipurpose prevention technologies, particularly
      those women who currently use contraception or are concerned about their risk of
      infection. Our results emphasize the importance of moving forward with MPT
      development as well as continued HIV/STI prevention education.

PMID- 29055783
TI  - Prenatal organochlorine pesticide exposure and the disruption of steroids and
      reproductive hormones in cord blood: The Hokkaido study.
AB  - Certain organochlorine pesticides (OCPs) are designated as persistent organic
      pollutants and are regulated in many countries. The effects of OCPs on pediatric
      endocrinology are a concern; however, only limited data exist from human studies
      on maternal OCP exposure and its effects on infants' hormone levels. This study
      was conducted as part of the Hokkaido Study Sapporo Cohort, a prospective birth
      cohort study in Japan. Participants included 514 women who enrolled at 23-35weeks
      of gestation between 2002 and 2005; maternal blood samples were collected in late
      pregnancy, and 29 OCPs were measured. Reproductive and steroid hormone levels in
      cord blood were also determined. Characteristics of mothers and their infants
      were obtained from self-administered questionnaires and medical records.
      Ultimately, 232 samples with both OCP and hormone data were analyzed. Fifteen of
      29 investigated OCPs were detected in over 80% of the samples, with p,p'
      dichlorodiphenyldichloroethylene showing the highest concentration (median value:
      619pg/g-wet). The association between OCPs and sex hormone levels varied by sex.
      Linear regression models after sex stratification showed that chlordanes, cis
      hexachlorobenzene, heptachlor epoxide, Mirex, and toxaphenes in maternal blood
      were inversely associated with testosterone, cortisol, cortisone, sex hormone
      binding globin, prolactin, and androstenedione-dehydroepiandrosterone (DHEA) and
      testosterone-androstenediones ratios among boys. Furthermore, these OCPs were
      positively correlated with DHEA, follicle stimulating hormone (FSH), and adrenal
      androgen-glucocorticoid and FSH-inhibin B ratios among boys. In categorical
      quartile models, testosterone and DHEA were inversely and positively associated
      with OCPs, respectively. Estradiol-testosterone and adrenal androgen
      glucocorticoid ratios tended to increase with increasing OCP concentrations in
      the higher quartile, while the testosterone-androstenedione ratio tended to
      decrease. Sex hormone-binding globulin and prolactin showed an inverse
      association with OCPs. Among girls, the linear regression model showed that only
      p,p'-dichlorodiphenyltrichloroethane was inversely associated with the level of
      DHEA and the adrenal androgen-glucocorticoid ratio, but was positively associated
      with cortisone levels. However, no associations were observed using the quartile
      categorical model. These results suggest that prenatal exposure to OCPs disrupt
      reproductive hormones of fetuses in utero among boys, even at relatively low
      levels.

PMID- 29055784
TI  - Rac1 modulates G-protein-coupled receptor-induced bronchial smooth muscle
      contraction.
AB  - Increasing evidence suggests a functional role of RhoA/Rho-kinase signalling as a
      mechanism for smooth muscle contraction; however, little is known regarding the
      roles of Rac1 and other members of the Rho protein family. This study aimed to
      examine whether Rac1 modulates bronchial smooth muscle contraction. Ring
      preparations of bronchi isolated from rats were suspended in an organ bath, and
      isometric contraction of circular smooth muscle was measured. Immunoblotting was
      used to examine myosin light chain phosphorylation in bronchial smooth muscle.
      Our results demonstrated that muscle contractions induced by carbachol (CCh) and
      endothelin-1 (ET-1) were inhibited by EHT1864, a selective Rac1 inhibitor, and
      NSC23766, a selective inhibitor of Rac1-specific guanine nucleotide exchange
      factors. Similarly, myosin light chain and myosin phosphatase target subunit 1
      (MYPT1) at Thr853 phosphorylation induced by contractile agonist were inhibited
      with Rac1 inhibition. However, contractions induced by high K+, calyculin A (a
      potent protein phosphatase inhibitor) and K+/PDBu were not inhibited by these
      Rac1 inhibitors. Interestingly, NaF (a G-protein activator)-induced contractions
      were inhibited by EHT1864 but not by NSC23766. We next examined the effects of a
      trans-acting activator of transcription protein transduction domain (PTD) fusion
      protein with Rac1 (PTD-Rac1) on muscle contraction. The constitutively active
      form of PTD-Rac1 directly induced force development and contractions were
      abolished by EHT1864. These results suggest that Rac1, activated by G protein
      coupled receptor agonists, such as CCh and ET-1, may induce myosin light chain
      and MYPT phosphorylation and modulate the contraction of bronchial smooth muscle.

PMID- 29055785
TI  - Probucol reverses homocysteine induced inflammatory monocytes differentiation and
      oxidative stress.
AB  - Reactive oxygen species have been demonstrated to involve in homocysteine-induced
      Ly-6Chi monocytes differentiation. Probucol is an anti-oxidant agent that has
      been used to treat atherosclerosis. We sought to evaluate the effect and
      potential mechanism of probucol on homocysteine-induced inflammatory monocytes
      differentiation. The primary mouse splenocytes suspensions were initiated by
      recombinant interferon-gamma and cultured with L-homocysteine in the presence or
      absence of probucol. The cells were co-incubated with monoclonal antibodies to
      CD11b-PE and Ly-6C FITC. Flow cytometry analysis was performed on BD FACS
      caliber. Data were analyzed using the FlowJo software. Mononuclear cells were
      gated according to the lower granular and larger size, distinguished with
      granulocytes and lymphocytes. Monocytes were defined as CD11b+ mononuclear cells
      and further divided into three groups based on their Ly-6C expressions, Ly-6Chi,
      Ly-6Cmid and Ly-6Clow subsets. The productions of reactive oxygen species in
      monocytes subsets were detected by 2',7'-dichlorofluorescein-diacetate (DCFH-DA)
      containing monocytes were marked as DCFH-DA+ cells in both Ly-6C+ and Ly-6C-
      subsets. The activity of nicotinamide adenine dinucleotide phosphate oxidase in
      THP-1 cells was measured by assay kit on enzyme-labelling instrument. L
      homocysteine promoted inflammatory monocytes differentiation and its reactive
      oxygen species productions in dose-dependent manner. Probucol dose-dependently
      suppressed the differentiation and reactive oxygen species productions of
      inflammatory monocytes induced by L-homocysteine. Furthermore, the increased
      NADPH oxidase activity induced by L-homocysteine was significantly reversed by
      probucol in THP-1 cells. Probucol prevented L-homocysteine-induced inflammatory
      monocytes differentiation and its reactive oxygen species generation probably
      through inhibiting NADPH oxidase activity.

PMID- 29055786
TI  - Carbon monoxide releasing molecule improves structural and functional cardiac
      recovery after myocardial injury.
AB  - Carbon monoxide (CO), produced by heme oxygenase-1 (HO-1), is an endogenous
      paracrine factor involved in the regulation of cardiovascular structure and
      function. We studied the effects of a synthetic CO releasing molecule (CORM-3) on
      cardiac recovery and myocardial microRNA expression after myocardial infarction
      (MI). Male Wistar rats with MI (n = 75) or sham-operated controls (n = 75) were
      treated from day 4 to day 14 after MI either with synthetic CORM-3 or with
      inactive iCORM and killed 2, 4 or 8 weeks post-MI. Infarct size, vascular and
      capillary densities, the amount of cardiomyocytes in the infarct area, and
      cardiomyocyte proliferation and apoptosis were determined. PCR was used for
      microRNA and mRNA quantification, western blotting to evaluate protein expression
      and echocardiography to assess cardiac structure and function. CORM-3 treatment
      increased vascular density (P< 0.05 vs. iCORM) and the proportion of
      cardiomyocytes (P< 0.05 vs. iCORM) in the infarct area. Ejection fraction
      improved (P< 0.05) and left ventricular volumes decreased (P< 0.05) in CORM-3
      treated MI groups compared to iCORM treatment. CORM-3 treatment decreased the
      amount of proliferating Ki67 positive cardiomyocytes in the infarct/border area
      at week 2 after MI compared to iCORM treatment, whereas the amount of apoptotic
      cardiomyocytes did not differ between CORM-3 and iCORM groups. Compared to iCORM
      treatment, CORM-3 decreased expression on miR-206 in the remote area at week 2
      after MI. The CO releasing molecule CORM-3 improved structural and functional
      cardiac recovery after MI. Modulation of HO-1-CO axis may prove novel drug
      targets to facilitate cardiac recovery after myocardial injury.

PMID- 29055787
TI  - Occurrence of a stonefish toxin-like toxin in the venom of the rabbitfish Siganus
      fuscescens.
AB  - Rabbitfish belonging to the order Perciformes are well-known venomous fish that
      are frequently involved in human accidents. However little research has been done
      into either the whole venom toxicities or the structures and properties of their
      venom toxins. In this study, we first examined biological activities of the crude
      venom extract prepared from dorsal spines of Siganus fuscescens, a rabbitfish
      most commonly found along the coasts of Japan. As a result, the crude venom
      extract was shown to have mouse-lethal activity, hemolytic activity against
      rabbit erythrocytes, edema-forming activity and nociceptive activity, similar to
      the known scorpaeniform fish toxins (stonefish toxins and their analogues). Then,
      the primary structure of the S. fuscescens toxin was successfully elucidated by
      the same cDNA cloning strategy as previously employed for the toxins of some
      scorpaeniform fish (lionfish, devil stinger and waspfish). The S. fuscescens
      toxin is obviously an analogue of stonefish toxins, being composed of two kinds
      of subunits, an alpha-subunit of 703 amino acid residues and a beta-subunit of
      699 amino acid residues. Furthermore, the genes encoding both subunits were
      cloned from genomic DNA and shown to have an architecture of three exons and two
      introns, as reported for those of the scorpaeniform fish toxins. This study is
      the first to demonstrate the occurrence of stonefish toxin-like toxins in
      perciform fish.

PMID- 29055788
TI  - Nitric oxide, malondialdheyde and non-enzymatic antioxidants assessed in viable
      spermatozoa from selected infertile men.
AB  - There are growing evidences that the semen of infertile male population shows
      higher reactive oxygen species (ROS) levels concomitant with lower antioxidant
      capacity compared to those detected in semen of fertile population. The plasma
      membrane of the sperm cell, which has high levels of polyunsaturated fatty acids,
      renders it particularly sensitive to ROS. The aim of this study was to compare
      the sperm parameters (concentration, motility, morphology and vitality) and the
      levels of malondialdehyde (MDA), as marker of lipid peroxidation (LPO), nitric
      oxide (NO), ascorbic acid (AA), total (GSHt) and oxidized glutathione (GSSG) in
      viable sperm in a group of 38 infertile patients and in a group of 55 control
      subjects with unknown reproductive potential. The comparison between variables in
      infertile patients and controls revealed that the sperm quality was reduced in
      the infertile group, whereas the levels of NO, AA and GSH were significantly
      increased in viable spermatozoa from infertile men; however, the endogenous
      levels of MDA were similar in infertile and control groups. Based on our results,
      we could speculate that the rise of GSHt and AA levels in viable sperm of
      infertile group help partially to counteract the damaging effect of ROS and
      partly prevent a substantial LPO. The observation of the concomitant increase of
      NO and antioxidant indices in viable spermatozoa of infertile subjects is a novel
      finding and we think that these results can be useful since the viable sperm
      population is conceivably used in assisted reproductive technology.

PMID- 29055789
TI  - In vitro studies on the role of recombinant human soluble thrombomodulin in the
      context of retinoic acid mediated APL differentiation syndrome.
AB  - Recombinant human soluble thrombomodulin (rTM) is a newly developed anti
      coagulant approved for treatment of disseminated intravascular coagulation (DIC)
      in Japan. rTM exerts anti-inflammatory and cytoprotective functions via its
      lectin-like and epidermal growth factor-like domains, respectively. In this
      study, we retrospectively reviewed the treatment of 21 consecutive patients with
      coagulopathy, complicated by acute promyelocytic leukemia (APL), with all-trans
      retinoic acid (ATRA) with or without combination with rTM. Surprisingly, none of
      the 14 rTM-treated patients developed retinoic acid (RA)-related differentiation
      syndrome (DS). The co-culture of vascular endothelial cell-derived EA.hy926 and
      APL-derived NB4 cells in the presence of RA increased production of tumor
      necrosis factor alpha (TNF-alpha) in culture media, in parallel with activation
      of p38 mitogen-activated protein kinase and increased levels of intracellular
      adhesion molecule 1 (ICAM1) in EA.hy926 cells. This was also associated with
      increased levels of the phosphorylated forms of VE-cadherin and enhanced vascular
      permeability of EA.hy926 monolayers. Importantly, addition of rTM to this co
      culture system inhibited the RA-induced phosphorylation of p38 and VE-cadherin
      and decreased ICAM1 and vascular permeability in EA.hy926 cells, without a
      decrease inthe levels of TNF-alpha. Taken together, use of rTM may be a promising
      treatment strategy to prevent DS in APL patients who receive ATRA.

PMID- 29055790
TI  - alpha-Actinin-4 confers radioresistance coupled invasiveness in breast cancer
      cells through AKT pathway.
AB  - Acquired radioresistance accompanied with increased metastatic potential is a
      major hurdle in effective radiotherapy of breast cancers. However, the nature of
      their inter-dependence and the underlying mechanism remains largely intangible.
      By employing radioresistant (RR) cell lines, we herein demonstrate that MCF-7 RR
      cells display phenotypic and molecular alterations evocative of epithelial to
      mesenchymal transition (EMT) with increased traction forces and membrane ruffling
      culminating in boosted invasiveness. We then show that these changes can be
      attributed to overexpression of alpha-actinin-4 (ACTN4), with ACTN4 knockdown
      near-completely abrogating both radioresistance and EMT-associated changes. We
      further found that in MCF-7 RR cells, ACTN4 mediates the observed effects by
      activating AKT, and downstream AKT/GSK3beta signalling. Though ACTN4 plays a
      similar role in mediating radioresistance and invasiveness in MDA-MB-231 RR
      cells, co-immunoprecipitation studies reveal that these changes are effected
      through increased association with AKT and not by overexpression of AKT. Taken
      together, our study identifies ACTN4/AKT/GSK3beta as a novel pathway regulating
      radioresistance coupled invasion which can be further explored to improve the
      radiotherapeutic gain.

PMID- 29055791
TI  - The role of decidual immune cells on human pregnancy.
AB  - The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow
      and develop in the uterus, despite being recognized by the maternal immune cells.
      Within the innate immune system, decidual natural killer cells and antigen
      presenting cells (including macrophages and dendritic cells) that comprise a
      large proportion of the decidual leukocyte populations play an important role in
      modulating trophoblast invasion, angiogenesis and vascular remodeling. On the
      other hand, within the adaptive immune system, CD8+ T cells, effector CD4+ T
      cells, Foxp3+ regulatory T cells and CD4+HLA-G+ suppressor T cells are identified
      as potential players in maintaining immune tolerance toward the semi-allogeneic
      fetus. This review discusses how these key immune cells contribute to pregnancy
      outcome and the complex interactions between the innate and adaptive immune
      system during human pregnancy.

PMID- 29055792
TI  - The effect of acetyl salicylic acid (Aspirin) on trophoblast-endothelial
      interaction in vitro.
AB  - Early administration of low dose acetyl salicylic acid (Aspirin) in high risk
      women reduces the risk of early onset preeclampsia. This study aims to
      investigate the effect of aspirin on trophoblast integration and the its effect
      on angiogenic and invasive pathways in an in-vitro model of preeclampsia. Red
      fluorescent-labeled human uterine myometrial microvascular endothelial cells
      (UtMVECs) were seeded on matrigel to form endothelial networks. Green fluorescent
      labeled trophoblastic HTR-8/SVneo cells were co-cultured with the endothelial
      networks with/without TNF-a (0.5ng/mL) and/or aspirin (0.1mM) for 24h.
      Fluorescent images were captured and quantified by Image J to examine the effects
      of TNF-a and aspirin on the trophoblast-endothelial integration. Conditioned
      media were collected to measure free VEGF, PlGF and sFlt-1 by ELISA and PGF1a by
      Enzyme immunoassay (EIA). Cells were retrieved to examine mRNA expression of
      angiogenic factors (VEGF, PlGF and sFlt-1), invasion markers (MMP-2 and TIMP-1),
      endothelial cell activation markers (E-selectin and VCAM), eNOS and
      cyclooxygenase (COX)-2 by quantitative PCR. Aspirin reversed the inhibitory
      effect of TNF-a on trophoblast cell integration into endothelial cellular
      networks. TNF-a increased PGF1a production (128+/-11%, p<0.05), whilst aspirin
      reversed the TNF-a effect on PGF1a production (19+/-4%, p<0.01). TNF-a decreased
      the mRNA expression of PlGF, eNOS, MMP-2 and TIMP-1, and stimulated COX2, E
      selectin and VCAM mRNA expression. Aspirin did not reverse the TNF-a effect on
      these molecules. Aspirin improves trophoblast cell integration into endothelial
      cellular networks by inhibiting the effect of TNF-a via PGI2 with no significant
      effect on antiangiogenic, invasive or endothelial activation markers.

PMID- 29055793
TI  - Synthesis of magnetite derivatives nanoparticles and their application for the
      removal of chromium (VI) from aqueous solutions.
AB  - Nowadays there is a continuously increasing worldwide concern for the development
      of efficient wastewaters treatment technologies. Among the heavy metal ions,
      chromium holds a distinct position due to its high toxic nature to biological
      systems. This study aims to assess magnetite derivatives nanoparticles for the
      removal of Cr(VI) species. Crystalline magnetite-rich (Magn) and pure maghemite
      (Magh) nanoparticles were produced by the polyol method and by subsequent heat
      treatment of Magn, respectively. The XRD analysis confirmed the formation of
      nanosized single phase cubic spinels with a cell parameter of 8.3710(2)A for Magn
      and 8.3401(2)A for Magh, consistent with those of a magnetite-rich ferrite and
      maghemite, respectively. TEM analysis showed that the two nanoferrites possessed
      comparable mean particle size of ~15nm. Magn and Magh showed superparamagnetic
      behavior at room temperature and reasonable saturation magnetizations at 300K of
      69 and 67emu.g-1, respectively. The Curie temperature of both nanoferrites
      exceeded 350 degrees C allowing the materials to work in severe conditions. Room
      temperature, batch adsorption experiments of Cr(VI) onto maghemite nanoparticles
      were carried out at pH 2.0. Adsorption efficiency increased rapidly was the
      increase of the nanoparticles dose. For a 20mg.L-1 Cr(VI) solution a 100% removal
      was found with ~3g.L-1 dose. Additionally, for a given dose (4.0g.L-1), the
      adsorption rate measured as a function of time for different Cr(VI)
      concentrations was very rapid; ~90% of removable Cr(VI) species was achieved
      within 10min. The high rate of Cr(VI) uptake takes advantages of the high active
      surface chemistry of the nanoparticles. The adsorption of Cr(VI) onto Magh
      nanoparticles followed a pseudo-second order kinetics indicating a chemisorption
      process. Further, the Langmuir isotherm model was found to best describe the
      equilibrium data with a maximum adsorption capacity of 12.5mg.g-1 for an
      adsorbent dosage of 4.0g.L-1.

PMID- 29055794
TI  - Facile synthesis of metal-organic frameworks/ordered mesoporous carbon composites
      with enhanced electrocatalytic ability for hydrazine.
AB  - The cooper-based metal-organic frameworks (Cu-MOFs) loaded on ordered mesoporous
      carbon (OMC) hybrids has been synthesized by a simple and rapid method for the
      first time. The composite materials were characterized comprehensively by SEM, X
      ray diffraction, Fourier transform infrared, nitrogen adsorption method, etc. The
      as-prepared novel Cu-MOFs/OMC nanohybrids extend the applications of support
      materials and provide new features of electrocatalytic activities. Hydrazine is
      performed as an electrochemical probe, which showed low limit of detection, wide
      linear range, and high sensitivity. The successful fabrication of Cu-MOFs/OMC
      holds great promise for the design of electrochemical sensors, and is a promising
      material to promote the development of new electrode materials.

PMID- 29055795
TI  - Small size mesoporous organosilica nanorods with different aspect ratios:
      Synthesis and cellular uptake.
AB  - In the work, small size thioether-bridged mesoporous organosilica nanorod (MONRs)
      are successfully synthesized using cetyltrimethylammonium bromide (CTAB) as
      structure-directing agent and bis[3-(triethoxysilyl)propyl]tetrasulfide (TETS)
      and tetraethoxysilane (TEOS) as co-precursors. The MONRs have tunable aspect
      ratios of 2, 3, and 4 (denoted as MONRs-2, MONRs-3, and MONRs-4), small and
      controllable lengths (75-310nm), high surface area (570-870cm2g-1), uniform
      mesopores (2.4-2.6nm), large pore volume (0.34cm3g-1), and excellent
      biocompatibility. The uptake of the MONRs by multidrug resistant human breast
      cancer MDR-MCF-7 cells is related to their aspect ratios. The MONRs-3 shows a
      faster and higher cellular internalization compared to the MONRs-4 and MONRs-2,
      respectively. Thanks to the high cellular uptake, doxorubicin (DOX) loaded MONRs
      3 show obviously improved chemotherapeutic effect on MDR-MCF-7 cancer cells. It
      is expected that the MONRs provide a useful platform for drug delivery and
      therapeutics.

PMID- 29055796
TI  - Dropwise addition of cation solution: An approach for growing high-quality
      upconversion nanoparticles.
AB  - A suitable synthetic route and the associated reaction parameters play a vital
      role for growing high-quality nanocrystal. A design strategy of injection was
      introduced with the aim of enhancing monodispersity and crystallinity of
      upconversion nanoparticles and making them have uniform morphology. The high
      quality Yb3+/Er3+-codoped LiYF4, NaYF4, KYF4 and NaGdF4 nanoparticles were
      synthesized by dropwise addition of cation solution into precursors mixture at
      high-temperature in this work. The detailed synthesis parameters of the purity
      tetragonal LiYF4:Yb3+/Er3+ upconversion nanoparticles in injection section were
      studied and ascertained. Changes of the injection temperature, reaction
      temperature, dropwise addition speed, mole ratio of cation (Li+) to precursors
      (RE(CF3COO)3), reaction time and reactants concentration have contributed much to
      synthesizing high-quality LiYF4:Yb3+/Er3+ in the end. Compared with traditional
      thermal decomposition method, a series of properties, such as high crystallinity,
      less agglomeration phenomenon, uniform tetragonal bipyramidal morphology and
      great upconversion luminescence, could be improved by this modified method.

PMID- 29055797
TI  - Solution-Processable transparent conducting electrodes via the self-assembly of
      silver nanowires for organic photovoltaic devices.
AB  - Solution-processed transparent conducting electrodes (TCEs) were fabricated via
      the self-assembly deposition of silver nanowires (Ag NWs). Glass substrates
      modified with (3-aminopropyl)triethoxysilane (APTES) and (3
      mercaptopropyl)trimethoxysilane (MPTES) were coated with Ag NWs for various
      deposition times, leading to three different Ag NWs samples (APTES-Ag NWs (PVP),
      MPTES-Ag NWs (PVP), and APTES-Ag NWs (COOH)). Controlling the deposition time
      produced Ag NWs monolayer thin films with different optical transmittance and
      sheet resistance. Post-annealing treatment improved their electrical
      conductivity. The Ag NWs films were successfully characterized using UV-Vis
      spectroscopy, field emission scanning electron microscopy, optical microscopy and
      four-point probe. Three Ag NWs films exhibited low sheet resistance of 4
      19Omega/sq and high optical transmittance of 65-81% (at 550nm), which are
      comparable to those of commercial ITO electrode. We fabricated an organic
      photovoltaic device by using Ag NWs as the anode instead of ITO electrode, and
      optimized device with Ag NWs exhibited power conversion efficiency of 1.72%.

PMID- 29055798
TI  - Prospective memory in bipolar disorder: A meta-analysis.
AB  - There are conflicting findings about prospective memory (PM) performance in
      bipolar disorder. This meta-analysis systematically examined PM in patients with
      bipolar disorders. Articles were systematically searched in both English and
      Chinese databases, from their inception to Nov 15, 2016. Only case-control
      studies on PM in bipolar patients were included for analyses. The random effect
      model was used in all meta-analytic outcomes. Four studies (n = 390) comparing PM
      performance between patients with bipolar disorder (n = 208) and healthy controls
      (n = 182) were included. Three studies were rated as "high quality", while the
      quality of evidence in 3 meta-analyzable outcomes ranged from "moderate" (67%) to
      "high" (33%). Compared to healthy controls, bipolar disorder patients showed
      impairments in overall PM [2 studies, n = 196; SMD: - 1.08 (95%CI: - 1.61, -
      0.55), P < 0.0001; I2 = 65%], event-based PM [4 studies, n = 367; SMD: - 0.51
      (95%CI: - 0.78, - 0.23), P = 0.0003; I2 = 37%] and time-based PM performance [4
      studies, n = 367; SMD: - 0.82 (95%CI: - 1.11, - 0.52), P < 0.0001; I2 = 41%]. In
      this meta-analysis, both time-based PM and event-based PM deficits appeared to be
      evident in bipolar disorder.

PMID- 29055799
TI  - Altered mGluR5 binding potential and glutamine concentration in the 6-OHDA rat
      model of acute Parkinson's disease and levodopa-induced dyskinesia.
AB  - Several lines of evidence point to alterations in glutamatergic signaling in
      Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), involving the
      metabotropic glutamate receptor type 5 (mGluR5). Using small-animal positron
      emission tomography (PET) with [18F]FPEB and proton magnetic resonance
      spectroscopy, we investigated cerebral changes in the mGluR5 and
      glutamate/glutamine availability in vivo in PD rats and following onset of LIDs.
      In parallel, behavioral tests were performed. Comparing PD to control rats,
      mGluR5 binding potential was decreased in a cluster comprising the bilateral
      caudate-putamen (CP), ipsilateral motor cortex and somatosensory cortex, and the
      contralateral somatosensory cortex and parietal association cortex, with the most
      pronounced reduction in the ipsilateral CP. mGluR5 binding potentials were not
      significantly altered upon levodopa (L-DOPA) treatment. However, following L
      DOPA, an increase in relative mGluR5 uptake was present in the contralateral
      motor cortex and somatosensory cortex. Glutamate and glutamine concentrations did
      not differ between control and untreated PD rats or between hemispheres. Though,
      glutamine levels were higher in the contralateral CP of saline- and L-DOPA
      treated rats as compared to the ipsilateral side. Relative mGluR5 uptake in the
      CP of levodopa-treated rats was also found positively correlated with abnormal
      involuntary movement scores. Conclusively, mGluR5 availability and glutamine
      concentrations in the CP are involved in PD, whereas mGluR5 availability in
      cortical regions may be involved in LID pathology.

PMID- 29055800
TI  - Anti-diabetic potential of peptides: Future prospects as therapeutic agents.
AB  - Diabetes mellitus is a metabolic disorder in which the glucose level in blood
      exceeds beyond the normal level. Persistent hyperglycemia leads to diabetes late
      complication and obviously account for a large number of morbidity and mortality
      worldwide. Numerous therapeutic options are available for the treatment of
      diabetes including insulin for type I and oral tablets for type II, but its
      effective management is still a dream. To date, several options are under
      investigation in various research laboratories for efficacious and safer agents.
      Of them, peptides are currently amongst the most widely investigated potential
      therapeutic agents whose design and optimal uses are under development. A number
      of natural and synthetic peptides have so far been found with outstanding
      antidiabetic effect mediated through diverse mechanisms. The applications of new
      emerging techniques and drug delivery systems further offer opportunities to
      achieve the desired target outcomes. Some outstanding peptides in preclinical and
      clinical studies with better efficacy and safety profile have already been
      identified. Further detail studies on these peptides may therefore lead to
      significant clinically useful antidiabetic agents.

PMID- 29055801
TI  - Hormone-induced rat model of polycystic ovary syndrome: A systematic review.
AB  - Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine
      disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms
      of this syndrome remain unclear. Considering the ethical limitations in human
      studies, animal models that reflect many features of PCOS are crucial resources
      to investigate this syndrome. We aimed to introduce the most suitable rat model
      of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of
      human PCOS phenotype, while maintaining normal reproductive system morphology in
      adulthood, in order to further more detailed investigations about PCOS. We
      searched Pubmed, Science direct, and Web of science between 1990 and 2016, for
      relevant English manuscripts, using keywords including the "Polycystic Ovary
      Syndrome AND Rat Model" to generate a subset of citations relevant to our
      research. Included were those articles that compared at least both ovarian
      histology or estrous cycle and reproductive hormonal profiles in hormone-induced
      rat model of PCOS and controls. Differences in the findings between hormone
      induced PCOS rats appear to be a result of the degree of transplacental transfer
      of the steroid administered into the fetus, dose and type of hormone, route of
      administration and timing and duration of exposure. We conclude that prenatal
      hormone-induced rat model with a lower dose and shorter time of exposure during
      the critical period of fetal development that exhibits endocrine, ovarian and
      metabolic disturbances similar to PCOS in women, while maintaining normal
      reproductive system morphology in adulthood is more suitable than postnatal
      hormone-induced rat model to facilitate studies regarding PCOS.

PMID- 29055802
TI  - Gefitinib and pyrrolidine dithiocarbamate decrease viral replication and cytokine
      production in dengue virus infected human monocyte cultures.
AB  - AIMS: The epidermal growth factor receptor (EGFR) and nucleotide-binding and
      oligomerization-domain containing 2 (NOD2) are important in cancer and in
      microbial recognition, respectively. These molecules trigger intracellular
      signaling pathways inducing the expression of inflammatory genes by NF-kB
      translocation. Gefitinib (GBTC) and pyrrolidine dithiocarbamate (PDTC) are
      capable of inhibiting EGFR/NOD2 and NF-kB, respectively. In earlier stages of
      dengue virus (DENV) infection, monocytes are capable of sustaining viral
      replication and increasing cytokine production, suggesting that
      monocyte/macrophages play an important role in early DENV replication. GBTC and
      PDTC have not been used to modify the pathogenesis of DENV in infected cells.
      This study was aimed to determine the effect of GBTC and PDTC on viral
      replication and cytokine production in DENV serotype 2 (DENV2)-infected human
      monocyte cultures. MAIN METHODS: GBTC and PDTC were used to inhibit EGFR/NOD2 and
      NF-kB, respectively. Cytokine production was measured by ELISA and viral
      replication by plaque forming unit assay. KEY FINDINGS: Increased DENV2
      replication and anti-viral cytokine production (IFN-alpha/beta, TNF-alpha, IL-12
      and IL-18) in infected cultures were found. These parameters were decreased after
      EGFR/NOD2 or NF-kB inhibitions. SIGNIFICANCE: The inhibitory effects of GBTC and
      PDTC on viral replication and cytokine production can be beneficial in the
      treatment of patients infected by dengue and suggest a possible role of EGFR/NOD2
      receptors and NF-kB in dengue pathogenesis.

PMID- 29055803
TI  - Optimal blood pressure decreases acute kidney injury after gastrointestinal
      surgery in elderly hypertensive patients: A randomized study: Optimal blood
      pressure reduces acute kidney injury.
AB  - STUDY OBJECTIVE: To determine the appropriate mean arterial pressure (MAP)
      control level for elderly patients with hypertension during the perioperative
      period. DESIGN: A prospective, randomized study. SETTING: Three teaching
      hospitals in China. PATIENTS: Six hundred seventy-eight elderly patients with
      chronic hypertension undergoing major gastrointestinal surgery. INTERVENTIONS:
      Patients were randomly allocated to three groups and the target MAP level was
      strictly controlled to one of three levels: level I (65-79mmHg), level II (80
      95mmHg), or level III (96-110mmHg). MEASUREMENTS: The primary outcome was acute
      kidney injury (AKI) (50% or 0.3mg.dL-1increase in creatinine level) during the
      first 7 postoperative days. The secondary outcomes were perioperative adverse
      complications. Moreover, vasoactive agents were observed during surgery. MAIN
      RESULTS: The overall incidence of postoperative AKI was 10.9% (71/648). AKI
      occurred significantly less often in patients with level II MAP control
      (6.3%;13/206) than in patients with level I (13.5%; 31/230) and level III (12.9%;
      27/210) (P<0.001) MAP control. Level II was associated with lower incidences of
      hospital-acquired pneumonia (6.7%; 14/206; P=0.014) and admission to the
      intensive care unit (ICU) (4.4%; 9/206; P=0.015) and with shorter length of stay
      in the ICU (P=0.025) when compared with level I and level III. Use of
      norepinephrine, phenylephrine, and nitroglycerin was significantly higher for
      patients with level III MAP control than for patients with level I and level II
      MAP control (P=0.001). CONCLUSIONS: For elderly hypertensive patients,
      controlling intraoperative MAP levels to 80 to 95mmHg can reduce postoperative
      AKI after major abdominal surgery.

PMID- 29055804
TI  - High homology is not required at the site of strand invasion during
      recombinational double-strand break repair in mammalian chromosomes.
AB  - We investigated the impact of sequence divergence on DNA double-strand break
      (DSB) repair occurring via recombination in cultured thymidine kinase deficient
      mouse fibroblasts. We stably transfected cells with a DNA construct harboring a
      herpes thymidine kinase (tk) gene (the "recipient") rendered nonfunctional by
      insertion of an oligonucleotide containing the recognition site for endonuclease
      I-SceI. The construct also contained a closely linked truncated "donor" tk
      sequence. The donor could potentially restore function to the recipient gene via
      recombination provoked by induction of a DSB at the I-SceI site in the recipient.
      Repair events were recoverable by selection for tk-positive clones. The donor
      contained 33 mismatches relative to the recipient. The mismatches were clustered,
      forming a localized segment of DNA sequence displaying about 20% divergence
      relative to the recipient, and the mismatched segment was surrounded by regions
      of high homology. When the donor was aligned with the recipient, the DSB site in
      the recipient aligned opposite the mismatched segment, allowing us to potentially
      capture recombinational repair events initiating between diverged sequences.
      Previous work demonstrated that mammalian cells effectively avoid recombination
      between 20% diverged sequences. In the current study we asked whether flanking
      regions of high homology would enable genetic exchange between highly diverged
      sequences or, instead, would rejection of exchange between diverged sequences
      remain unchanged. We found that by surrounding mismatches with high homology,
      suppression of recombination between diverged sequences was overcome. Strikingly,
      we recovered a high frequency of gene conversion tracts positioned entirely
      within the mismatched sequences. We infer that such events were enabled by
      homologous pairing interactions between sequences surrounding the site of strand
      invasion. Our results suggest a search for high homology prior to recombination
      that is not mediated by an invading DNA terminus.

PMID- 29055805
TI  - "People try and label me as someone I'm not": The social ecology of Indigenous
      people living with HIV, stigma, and discrimination in Manitoba, Canada.
AB  - Indigenous peoples (First Nations, Inuit, and Metis) are currently
      overrepresented in the HIV epidemic in Canada and are infected at a younger age
      than those who are not Indigenous. This article presents our findings on the
      stigma and discrimination (as well as related themes such as disclosure)
      experienced by Indigenous people who contracted HIV in their youth and live in
      urban and non-urban settings in Manitoba, Canada. The findings were derived from
      a qualitative study that sought to understand the experiences and needs of
      Indigenous people living with HIV (including AIDS). We situate such experiences
      within a social ecological framework towards developing a better structural
      understanding of the impacts of stigma and discrimination on the lives of
      Indigenous people who are HIV positive. Stigma and discrimination caused barriers
      for Indigenous people living with HIV through inhibiting their ease of access to
      supports including family, peers, community, and long- and short-term health
      services. Creative forms of outreach and education that are culturally
      appropriate and/or rooted in culture were considered to be possibly impactful
      ways of reducing stigma and discrimination at the community level. Learning from
      communities who are successfully managing stigma also showed promise for
      developing new programming.

PMID- 29055806
TI  - New generation of docking programs: Supercomputer validation of force fields and
      quantum-chemical methods for docking.
AB  - Discovery of new inhibitors of the protein associated with a given disease is the
      initial and most important stage of the whole process of the rational development
      of new pharmaceutical substances. New inhibitors block the active site of the
      target protein and the disease is cured. Computer-aided molecular modeling can
      considerably increase effectiveness of new inhibitors development. Reliable
      predictions of the target protein inhibition by a small molecule, ligand, is
      defined by the accuracy of docking programs. Such programs position a ligand in
      the target protein and estimate the protein-ligand binding energy. Positioning
      accuracy of modern docking programs is satisfactory. However, the accuracy of
      binding energy calculations is too low to predict good inhibitors. For effective
      application of docking programs to new inhibitors development the accuracy of
      binding energy calculations should be higher than 1kcal/mol. Reasons of limited
      accuracy of modern docking programs are discussed. One of the most important
      aspects limiting this accuracy is imperfection of protein-ligand energy
      calculations. Results of supercomputer validation of several force fields and
      quantum-chemical methods for docking are presented. The validation was performed
      by quasi-docking as follows. First, the low energy minima spectra of 16 protein
      ligand complexes were found by exhaustive minima search in the MMFF94 force
      field. Second, energies of the lowest 8192 minima are recalculated with CHARMM
      force field and PM6-D3H4X and PM7 quantum-chemical methods for each complex. The
      analysis of minima energies reveals the docking positioning accuracies of the PM7
      and PM6-D3H4X quantum-chemical methods and the CHARMM force field are close to
      one another and they are better than the positioning accuracy of the MMFF94 force
      field.

PMID- 29055807
TI  - Ivermectin reduces motor coordination, serum testosterone, and central
      neurotransmitter levels but does not affect sexual motivation in male rats.
AB  - Ivermectin (IVM) is a macrocyclic lactone used for the treatment of parasitic
      infections and widely used in veterinary medicine as endectocide. In mammals,
      evidence indicates that IVM interacts with gamma-aminobutyric acid (GABA)
      mediated chloride channels. GABAergic system is involved in the manifestation of
      sexual behavior. We previously found that IVM at therapeutic doses did not alter
      sexual behavior in male rats, but at a higher dose, the appetitive phase of
      sexual behavior was impaired. Thus, we investigated whether the reduction of
      sexual behavior that was previously observed was a consequence of motor or
      motivational deficits that are induced by IVM. Data showed significant decrease
      in striatal dopaminergic system activity and lower testosterone levels but no
      effects on sexual motivation or penile erection. These findings suggest IVM may
      activate the GABAergic system and reduce testosterone levels, resulting in a
      reduction of motor coordination as consequence of the inhibition of striatal
      dopamine release.

PMID- 29055808
TI  - Tocopherol and selenite modulate the transplacental effects induced by sodium
      arsenite in hamsters.
AB  - Human studies suggest that in utero exposure to arsenic results in adverse
      pregnancy outcomes. The use of dietary supplements, such as sodium selenite (SS)
      or alpha-tocopherol succinate (alpha-TOS), is a reasonable approach to ameliorate
      such health effects. Sodium arsenite at 100ppm was administered via drinking
      water to female hamsters from gestational days 1 or 8 to the time of delivery.
      Viable fetuses, fetal resorptions and non-viable fetuses were recorded during and
      after pregnancy and total arsenic and its metabolites were characterized in
      pregnant animals, placentas and fetuses. Arsenic was found to accumulate in the
      placenta and fetus, increasing fetal mortality, non-viable fetuses and
      resorptions. Co-administration of SS and alpha-TOS significantly reduced the
      observed teratogenic effects. SS influenced arsenic biotransformation by reducing
      the MMA/InAs index and increasing the DMA/MMA, whereas alpha-TOS more likely
      exerts its protective effect through its potent antioxidant activity.

PMID- 29055809
TI  - Neonatal exposure to estradiol valerate reprograms the rat ovary androgen
      receptor and anti-Mullerian hormone to a polycystic ovary phenotype.
AB  - To understand the impact of exposure to steroids in the early step of ovary
      development (a stage occurring in uterus in humans), we studied neonatal exposure
      to estradiol valerate (EV) in rats regarding polycystic ovary (PCO) development
      as well as expression of androgen receptor (Ar) and anti-Mullerian hormone (AMH),
      a marker of ovarian follicular development. Rats exposed to one dose of EV
      (10mg/kg, sc) during their first 12h of life were euthanized at 2, 30 and 60days
      of age. Gene array and real-time PCR studies showed Ar and AMH up regulation in
      the ovary at 2days of age and persisted at 60days of age, when a PCO phenotype
      was evident with increased levels of Ar and AMH proteins. The single neonatal
      exposure in rats suggests participation of EV in developing PCO syndrome. Its
      persistence also suggests that estradiol reprograms ovarian function and disease
      during adulthood.

PMID- 29055810
TI  - Prenatal caffeine ingestion increases susceptibility to pulmonary inflammation in
      adult female rat offspring.
AB  - This study aimed to investigate the association between prenatal caffeine
      ingestion (PCI) and risk of postnatal pulmonary inflammation. Pregnant Wistar
      rats were administered 60mg/kg/d caffeine intragastrically from gestational day
      (GD) 7 to GD 20. The results showed that PCI obviously increased intrauterine
      growth retardation rate to 39.2% and suppressed weight growth of the offspring.
      PCI also enhanced the expression of transforming growth factor beta, alpha-smooth
      muscle actin, interleukin (IL)-1beta, and IL-8 in lungs and caused pulmonary
      interstitial thickening in the offspring. Further, with lipopolysaccharide
      stimulation on postnatal day 77, PCI offspring showed more serious inflammatory
      infiltration, higher injury scores, and higher levels of IL-6 and tumor necrosis
      factor-alpha in lungs than those of the control. Our findings showed, for the
      first time, that PCI is a certainly threat to postnatal pulmonary inflammation.
      The potential mechanism is that PCI alter the expression of pulmonary
      interstitial thickening-associated genes in the offspring.

PMID- 29055811
TI  - Access to treatment with controlled medicines rationale and recommendations for
      neutral, precise, and respectful language.
AB  - The European Pain Federation EFIC, the International Association for Hospice and
      Palliative Care, International Doctors for Healthier Drug Policies, the Swiss
      Romandy College for Addiction Medicine, the Swiss Society of Addiction Medicine,
      and the World Federation for the Treatment of Opioid Dependence called on medical
      journals to ensure that authors always use terminology that is neutral, precise,
      and respectful in relation to the use of psychoactive substances. It has been
      shown that language can propagate stigma, and that stigma can prevent people from
      seeking help and influence the effectiveness of social and public-health
      policies. The focus of using appropriate terminology should extend to all
      patients who need controlled medicines, avoiding negative wording. A narrow focus
      on a few terms and medical communication only should be avoided. The
      appropriateness of terms is not absolute and indeed varies between cultures and
      regions and over time. For this reason, it is important that communities
      establish their own consensus of what is 'neutral', 'precise', and 'respectful'.
      We identified twenty-three problematic terms (most of them we suggest avoiding)
      and their possible alternatives. The use of appropriate language improves
      scientific quality of articles and increases chances that patients will receive
      the best treatment and that government policies on psychoactive substance
      policies will be rational.

PMID- 29055814
TI  - Multidomain lifestyle intervention benefits a large elderly population at risk
      for cognitive decline and dementia regardless of baseline characteristics: The
      FINGER trial.
AB  - INTRODUCTION: The 2-year Finnish Geriatric Intervention Study to Prevent
      Cognitive Impairment and Disability (FINGER) multidomain lifestyle intervention
      trial (NCT01041989) demonstrated beneficial effects on cognition. We investigated
      whether sociodemographics, socioeconomic status, baseline cognition, or
      cardiovascular factors influenced intervention effects on cognition. METHODS: The
      FINGER recruited 1260 people from the general Finnish population (60-77 years, at
      risk for dementia). Participants were randomized 1:1 to multidomain intervention
      (diet, exercise, cognition, and vascular risk management) and regular health
      advice. Primary outcome was change in cognition (Neuropsychological Test Battery
      z-score). Prespecified analyses to investigate whether participants'
      characteristics modified response to intervention were carried out using mixed
      model repeated-measures analyses. RESULTS: Sociodemographics (sex, age, and
      education), socioeconomic status (income), cognition (Mini-Mental State
      Examination), cardiovascular factors (body mass index, blood pressure,
      cholesterol, fasting glucose, and overall cardiovascular risk), and
      cardiovascular comorbidity did not modify response to intervention (P-values for
      interaction > .05). CONCLUSIONS: The FINGER intervention was beneficial
      regardless of participants' characteristics and can thus be implemented in a
      large elderly population at increased risk for dementia.

PMID- 29055812
TI  - Progress toward standardized diagnosis of vascular cognitive impairment:
      Guidelines from the Vascular Impairment of Cognition Classification Consensus
      Study.
AB  - INTRODUCTION: Progress in understanding and management of vascular cognitive
      impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting
      the use of multiple different assessment protocols. A large multinational group
      of clinicians and researchers participated in a two-phase Vascular Impairment of
      Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS
      1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. METHODS:
      We used VICCCS-1 principles and published diagnostic guidelines as points of
      reference for an online Delphi survey aimed at achieving consensus on clinical
      diagnosis of VCI. RESULTS: Six survey rounds comprising 65-79 participants agreed
      guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and
      endorsed the National Institute of Neurological Disorders-Canadian Stroke Network
      neuropsychological assessment protocols and recommendations for imaging.
      DISCUSSION: The VICCCS-2 suggests standardized use of the National Institute of
      Neurological Disorders-Canadian Stroke Network recommendations on
      neuropsychological and imaging assessment for diagnosis of VCI so as to promote
      research collaboration.

PMID- 29055813
TI  - Amyloid beta synaptotoxicity is Wnt-PCP dependent and blocked by fasudil.
AB  - INTRODUCTION: Synapse loss is the structural correlate of the cognitive decline
      indicative of dementia. In the brains of Alzheimer's disease sufferers, amyloid
      beta (Abeta) peptides aggregate to form senile plaques but as soluble peptides
      are toxic to synapses. We previously demonstrated that Abeta induces Dickkopf-1
      (Dkk1), which in turn activates the Wnt-planar cell polarity (Wnt-PCP) pathway to
      drive tau pathology and neuronal death. METHODS: We compared the effects of Abeta
      and of Dkk1 on synapse morphology and memory impairment while inhibiting or
      silencing key elements of the Wnt-PCP pathway. RESULTS: We demonstrate that Abeta
      synaptotoxicity is also Dkk1 and Wnt-PCP dependent, mediated by the arm of Wnt
      PCP regulating actin cytoskeletal dynamics via Daam1, RhoA and ROCK, and can be
      blocked by the drug fasudil. DISCUSSION: Our data add to the importance of
      aberrant Wnt signaling in Alzheimer's disease neuropathology and indicate that
      fasudil could be repurposed as a treatment for the disease.

PMID- 29055815
TI  - Evidence for brain glucose dysregulation in Alzheimer's disease.
AB  - INTRODUCTION: It is unclear whether abnormalities in brain glucose homeostasis
      are associated with Alzheimer's disease (AD) pathogenesis. METHODS: Within the
      autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain
      glucose concentration and assessed the ratios of the glycolytic amino acids,
      serine, glycine, and alanine to glucose. We also quantified protein levels of the
      neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we
      assessed the relationships between plasma glucose measured before death and brain
      tissue glucose. RESULTS: Higher brain tissue glucose concentration, reduced
      glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the
      expression of AD symptoms. Longitudinal increases in fasting plasma glucose
      levels are associated with higher brain tissue glucose concentrations.
      DISCUSSION: Impaired glucose metabolism due to reduced glycolytic flux may be
      intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may
      begin several years before the onset of clinical symptoms.

PMID- 29055816
TI  - Alzheimer's Disease Sequencing Project discovery and replication criteria for
      cases and controls: Data from a community-based prospective cohort study with
      autopsy follow-up.
AB  - INTRODUCTION: The Alzheimer's Disease Sequencing Project (ADSP) used different
      criteria for assigning case and control status from the discovery and replication
      phases of the project. We considered data from a community-based prospective
      cohort study with autopsy follow-up where participants could be categorized as
      case, control, or neither by both definitions and compared the two sets of
      criteria. METHODS: We used data from the Adult Changes in Thought (ACT) study
      including Diagnostic and Statistical Manual-IV criteria for dementia status,
      McKhann et al. criteria for clinical Alzheimer's disease, and Braak and
      Consortium to Establish a Registry for AD findings on neurofibrillary tangles and
      neuritic plaques to categorize the 621 ACT participants of European ancestry who
      died and came to autopsy. We applied ADSP discovery and replication definitions
      to identify controls, cases, and people who were neither controls nor cases.
      RESULTS: There was some agreement between the discovery and replication
      definitions. Major areas of discrepancy included the finding that only 40% of the
      discovery sample controls had sufficiently low levels of neurofibrillary tangles
      and neuritic plaques to be considered controls by the replication criteria and
      the finding that 16% of the replication phase cases were diagnosed with non-AD
      dementia during life and thus were excluded as cases for the discovery phase.
      CONCLUSIONS: These findings should inform interpretation of genetic association
      findings from the ADSP. Differences in genetic association findings between the
      two phases of the study may reflect these different phenotype definitions from
      the discovery and replication phase of the ADSP.

PMID- 29055817
TI  - Retroperitoneal nodal metastasis in primary adult type granulosa cell tumor of
      the ovary: Can routine lymphadenectomy be omitted?
AB  - OBJECTIVE: To investigate the incidence of retroperitoneal lymph node metastasis
      among patients with primary adult type granulosa cell tumor (AGCT) of the ovary.
      STUDY DESIGN: Between January 1982 and February 2017, patients with a
      pathological diagnosis of AGCT were identified. Clinical and pathological data
      were obtained from database records. RESULTS: A total of 151 patients with
      primary AGCT were identified with a mean age of 47.8 years (range, 17-91 years).
      98 patients (64.9%) had stage IA, 24 (15.9%) had stage IC, 4 (2.6%) had stage
      IIB, 2 (1.3%) had stage IIIB, 6 (4.0%) had stage IIIC disease according to
      International Federation of Gynecology and Obstetrics (FIGO) 1988 criteria. In
      the remaining 17 patients (11.3%), primary stage was not detected. In 134 (88.7%)
      patients, pelvic and para-aortic lymphadenectomy was performed at primary staging
      surgery depending on the frozen section analysis or at re-staging surgery
      following initial diagnosis. In these patients, six (4.5%) of them had pelvic or
      paraaortic lymph node metastasis. The median number of lymph nodes removed was 43
      (range, 10-96 lymph nodes). CONCLUSION: Lymph node metastasis in initially staged
      AGCT is rare. Routine pelvic and paraaortic lymph node dissection may be omitted
      in these patients.

PMID- 29055818
TI  - Comparative transcriptome analysis reveals multiple functions for Mhy1p in lipid
      biosynthesis in the oleaginous yeast Yarrowia lipolytica.
AB  - Yarrowia lipolytica is considered as a promising microbial cell factory for bio
      oil production due to its ability to accumulate a large amount of lipid. However,
      the regulation of lipid metabolism in this oleaginous yeast is elusive. In this
      study, the MHY1 gene was disrupted, and 43.1% (w/w) intracellular oil based on
      cell dry weight was obtained from the disruptant M-MHY1, while only 30.2% (w/w)
      lipid based on cell dry weight was obtained from the reference strain. RNA-seq
      was then performed to analyze transcriptional changes during lipid biosynthesis
      after MHY1 gene inactivation. The expression of 1597 genes, accounting for 24.7%
      of annotated Y. lipolytica genes, changed significantly in the disruptant M-MHY1
      during lipid biosynthesis. Differential gene expression analysis indicated that
      Mhy1p performs multiple functions and participates in a wide variety of
      biological processes, including lipid, amino acid and nitrogen metabolism.
      Notably, data analysis revealed increased carbon flux through lipid biosynthesis
      following MHY1 gene inactivation, accompanied by decreased carbon flux through
      amino acid biosynthesis. Moreover, Mhy1p regulates the cell cycle, and the cell
      cycle rate was enhanced in the disruptant M-MHY1. These results suggest that
      Mhy1p plays critical regulatory roles in diverse aspects of various biological
      processes, especially in lipid biosynthesis, amino acid and nitrogen metabolism
      and cell cycle. Our dataset appears to elucidate the crucial role of Mhy1p in
      lipid biosynthesis and serves as a resource for exploring physiological dimorphic
      growth in Y. lipolytica.

PMID- 29055819
TI  - Dynamics of lentiviral infection in vivo in the absence of adaptive immune
      responses.
AB  - Understanding the dynamics of acute viral infection is crucial for developing
      strategies to prevent and control infection. In this study, lentiviral dynamics
      in a host without adaptive immunity were examined in order to determine kinetic
      parameters of infection and quantify the effect of neutralizing antibodies in
      preventing infection, using mathematical modeling of data from equine infectious
      anemia virus (EIAV) infection of horses with severe combined immunodeficiency
      (SCID). Estimated parameters were used to calculate the basic reproductive number
      and virus doubling time and found that the rate that antibodies neutralized virus
      was ~18 times greater than the virus clearance rate. These results establish EIAV
      replication kinetics in SCID horses and the minimal efficacy of antibodies that
      blocked infection. Furthermore, they indicate that EIAV is at most mildly
      cytopathic. This study advances our understanding of EIAV infection and may have
      important implications for the control of other viral infections, including HIV.

PMID- 29055820
TI  - IgG glycosylation and DNA methylation are interconnected with smoking.
AB  - BACKGROUND: Glycosylation is one of the most common post-translation
      modifications with large influences on protein structure and function. The
      effector function of immunoglobulin G (IgG) alters between pro- and anti
      inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex
      and dynamic. METHODS: With the use of two different analytical methods for
      assessing IgG glycosylation, we aim to elucidate the link between DNA methylation
      and glycosylation of IgG by means of epigenome-wide association studies. In
      total, 3000 individuals from 4 cohorts were analyzed. RESULTS: The overlap of the
      results from the two glycan measurement panels yielded DNA methylation of 7 CpG
      sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904
      (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921
      (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation
      analyses with respect to smoking revealed that the effect of smoking on IgG
      glycosylation may be at least partially mediated via DNA methylation levels at
      these 7 CpG-sites. CONCLUSION: Our results suggest the presence of an indirect
      link between DNA methylation and IgG glycosylation that may in part capture
      environmental exposures. GENERAL SIGNIFICANCE: An epigenome-wide analysis
      conducted in four population-based cohorts revealed an association between DNA
      methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates
      the effect of smoking on IgG glycosylation.

PMID- 29055822
TI  - Anabolic steroid use among gay and bisexual men living in Australia and New
      Zealand: Associations with demographics, body dissatisfaction, eating disorder
      psychopathology, and quality of life.
AB  - BACKGROUND AND AIMS: Gay and bisexual men may be at heightened risk for using
      anabolic androgenic steroids (AAS). Few studies, however, have examined AAS use
      among gay and bisexual men living in countries outside the United States. In
      addition, few studies have explored the potential associations of AAS use with
      body image concerns beyond muscularity, including height and genitals, or with
      eating disorder symptoms and quality of life. Thus, we examined the associations
      of AAS use, and of thoughts about using AAS, with body image, eating disorder
      symptoms, and quality of life among gay and bisexual men living in Australia and
      New Zealand. METHODS: A sample of 2733 gay and bisexual men completed an online
      survey promoted by paid nationwide advertisements to users of geosocial
      networking smartphone applications. RESULTS: The prevalence of AAS use, and of
      thoughts about using AAS, were 5.2% (95% confidence interval [CI]: 4.4%, 6.1%)
      and 25.4% (95% CI: 23.8%, 27.1%), respectively. Multivariate analyses revealed
      that more frequent thoughts about using AAS were associated with being older,
      taller, and experiencing greater dissatisfaction with muscularity and height,
      less dissatisfaction with body fat, greater eating disorder symptoms, and lower
      subjective quality of life. Actual AAS users were more likely to be older, from a
      non-Australian/New Zealander cultural background, experiencing less
      dissatisfaction with body fat, and experiencing greater eating disorder symptoms.
      CONCLUSIONS: Psychopathology related to body image and eating disorders are
      associated with AAS use among gay and bisexual men living in Australia and New
      Zealand.

PMID- 29055821
TI  - Prevalence and pathways of recovery from drug and alcohol problems in the United
      States population: Implications for practice, research, and policy.
AB  - BACKGROUND: Alcohol and other drug (AOD) problems confer a global, prodigious
      burden of disease, disability, and premature mortality. Even so, little is known
      regarding how, and by what means, individuals successfully resolve AOD problems.
      Greater knowledge would inform policy and guide service provision. METHOD:
      Probability-based survey of US adult population estimating: 1) AOD problem
      resolution prevalence; 2) lifetime use of "assisted" (i.e., treatment/medication,
      recovery services/mutual help) vs. "unassisted" resolution pathways; 3)
      correlates of assisted pathway use. Participants (response=63.4% of 39,809)
      responding "yes" to, "Did you use to have a problem with alcohol or drugs but no
      longer do?" assessed on substance use, clinical histories, problem resolution.
      RESULTS: Weighted prevalence of problem resolution was 9.1%, with 46% self
      identifying as "in recovery"; 53.9% reported "assisted" pathway use. Most
      utilized support was mutual-help (45.1%,SE=1.6), followed by treatment
      (27.6%,SE=1.4), and emerging recovery support services (21.8%,SE=1.4), including
      recovery community centers (6.2%,SE=0.9). Strongest correlates of "assisted"
      pathway use were lifetime AOD diagnosis (AOR=10.8[7.42-15.74], model R2=0.13),
      drug court involvement (AOR=8.1[5.2-12.6], model R2=0.10), and, inversely,
      absence of lifetime psychiatric diagnosis (AOR=0.3[0.2-0.3], model R2=0.10).
      Compared to those with primary alcohol problems, those with primary cannabis
      problems were less likely (AOR=0.7[0.5-0.9]) and those with opioid problems were
      more likely (AOR=2.2[1.4-3.4]) to use assisted pathways. Indices related to
      severity were related to assisted pathways (R2<0.03). CONCLUSIONS: Tens of
      millions of Americans have successfully resolved an AOD problem using a variety
      of traditional and non-traditional means. Findings suggest a need for a
      broadening of the menu of self-change and community-based options that can
      facilitate and support long-term AOD problem resolution.

PMID- 29055823
TI  - Neutrophil granule proteins generate bactericidal ammonia chloramine on reaction
      with hydrogen peroxide.
AB  - The neutrophil enzyme, myeloperoxidase, by converting hydrogen peroxide (H2O2)
      and chloride to hypochlorous acid (HOCl), provides important defense against
      ingested micro-organisms. However, there is debate about how efficiently HOCl is
      produced within the phagosome and whether its reactions with phagosomal
      constituents influence the killing mechanism. The phagosome is a small space
      surrounding the ingested organism, into which superoxide, H2O2 and high
      concentrations of proteins from cytoplasmic granules are released. Previous
      studies imply that HOCl is produced in the phagosome, but a large proportion
      should react with proteins before reaching the microbe. To mimic these
      conditions, we subjected neutrophil granule extract to sequential doses of H2O2.
      Myeloperoxidase in the extract converted all the H2O2 to HOCl, which reacted with
      the granule proteins. 3-Chlorotyrosine, protein carbonyls and large amounts of
      chloramines were produced. At higher doses of H2O2, the extract developed potent
      bactericidal activity against Staphylococcus aureus. This activity was due to
      ammonia monochloramine, formed as a secondary product from protein chloramines
      and dichloramines. Isolated myeloperoxidase and elastase also became bactericidal
      when modified with HOCl and antibacterial activity was seen with a range of
      species. Comparison of levels of protein modification in the extract and in
      phagosomes implies that a relatively low proportion of phagosomal H2O2 would be
      converted to HOCl, but there should be sufficient for substantial protein
      chloramine formation and some breakdown to ammonia monochloramine. It is possible
      that HOCl could kill ingested bacteria by an indirect mechanism involving protein
      oxidation and monochloramine formation.

PMID- 29055824
TI  - Selenium-containing indolyl compounds: Kinetics of reaction with inflammation
      associated oxidants and protective effect against oxidation of extracellular
      matrix proteins.
AB  - Activated white blood cells generate multiple oxidants in response to invading
      pathogens. Thus, hypochlorous acid (HOCl) is generated via the reaction of
      myeloperoxidase (from neutrophils and monocytes) with hydrogen peroxide, and
      peroxynitrous acid (ONOOH), a potent oxidizing and nitrating agent is formed from
      superoxide radicals and nitric oxide, generated by stimulated macrophages.
      Excessive or misplaced production of these oxidants has been linked to multiple
      human pathologies, including cardiovascular disease. Atherosclerosis is
      characterized by chronic inflammation and the presence of oxidized materials,
      including extracellular matrix (ECM) proteins, within the artery wall. Here we
      investigated the potential of selenium-containing indoles to afford protection
      against these oxidants, by determining rate constants (k) for their reaction, and
      quantifying the extent of damage on isolated ECM proteins and ECM generated by
      human coronary artery endothelial cells (HCAECs). The novel selenocompounds
      examined react with HOCl with k 0.2-1.0 * 108M-1s-1, and ONOOH with k 4.5-8.6 - *
      105M-1s-1. Reaction with H2O2 is considerably slower (k < 0.25M-1s-1). The
      selenocompound 2-phenyl-3-(phenylselanyl)imidazo[1,2-a]pyridine provided
      protection to human serum albumin (HSA) against HOCl-mediated damage (as assessed
      by SDS-PAGE) and damage to isolated matrix proteins induced by ONOOH, with a
      concomitant decrease in the levels of the biomarker 3-nitrotyrosine. Structural
      damage and generation of 3-nitroTyr on HCAEC-ECM were also reduced. These data
      demonstrate that the novel selenium-containing compounds show high reactivity
      with oxidants and may modulate oxidative and nitrosative damage at sites of
      inflammation, contributing to a reduction in tissue dysfunction and
      atherogenesis.

PMID- 29055825
TI  - Analysis of endogenous H2S and H2Sn in mouse brain by high-performance liquid
      chromatography with fluorescence and tandem mass spectrometric detection.
AB  - Previous studies indicated that bound sulfur species (BSS), including hydrogen
      polysulfide (H2Sn), have various physiological functions in mammalian cells.
      Although H2Sn molecules have been considered as secondary metabolites derived
      from hydrogen sulfide (H2S) based on in vitro studies or predetermined reaction
      formula, the physiological form of BSS and their endogenous concentration remain
      unclear. In the present study, we aimed to improve the usual method using
      monobromobimane (mBB) followed by high performance liquid chromatographic (HPLC)
      analysis for HS- for simultaneous determination of H2S, H2S2, H2S3 and cysteine
      persulfide in biological samples. We demonstrated that mBB derivatization of H2S
      and H2Sn standards under alkaline conditions (pH 9.5) induced significant
      decreases in H2S2 and H2S3 levels and a significant increase in the H2S level in
      an incubation time-dependent manner. Conversely, the derivatization of mBB
      adducts of H2S2 and H2S3 were stable under neutral conditions (pH 7.0), which is
      physiologically relevant. Therefore, we re-examined the method using mBB and
      applied an improved method for the evaluation of H2S, H2S2, and H2S3 in mouse
      brain under physiological pH conditions. The concentrations of H2S and H2S2 were
      0.030 +/- 0.004MUmol/g protein and 0.026 +/- 0.002MUmol/g protein, respectively.
      Although the level of H2S3 was below the quantification limit of this method,
      H2S3 was detected in mouse brain. Using the method established here, we reveal
      for the first time the existence of endogenous H2S2 and H2S3 in mammalian brain
      tissues. H2S2 and H2S3 exert anti-oxidant activity and anti-carbonyl stress
      effects through the regulation of redox balance in neuronal cells. Thus, our
      observations provide novel insights into the physiological functions of BSS in
      the brain and into neuronal diseases involved in redox imbalance.

PMID- 29055826
TI  - Fathers' repetition of words is coupled with children's vocabularies.
AB  - Differences in vocabulary size among children can be explained in part by
      differences in parents' language input, but features of caregivers' input can be
      more or less beneficial depending on children's language abilities. The current
      study focused on a specific feature of infant-directed speech: parents'
      repetition of words across utterances. Although previous work with infants showed
      a positive relation between repetition and children's vocabulary, we predicted
      that this would not be the case later in development. Instead, parents may use
      less repetition as their children become increasingly proficient language
      learners. In the current study, we examined the extent to which low-income
      fathers of 24-month-olds (N=41) repeat words to their children using three
      indices: type-token ratio, automated repetition index, and partial repetition of
      open-class words. The same finding emerged across all measures of repetition:
      Fathers whose children had larger vocabularies at 24months repeated
      wordslessoften, suggesting a developmental coupling of fathers' input and
      children's language proficiency.

PMID- 29055827
TI  - Using stable isotope labeling to study the nitrogen metabolism in Anabaena flos
      aquae growth and anatoxin biosynthesis.
AB  - Freshwater resources are under stress around the world due to rapid urbanization
      and excessive water consumption. Cyanobacterial blooms have occurred frequently
      in surface waters, which produced toxic secondary metabolites causing a potential
      harm to aquatic ecosystems and humans. In this study, the relationship between
      different types of nitrogen source and the algal growth of Anabaena flos-aquae,
      which was isolated from Dianchi Lake in southern China, was investigated.
      Experiments were accomplished by using four types of isotope tracers including
      15N-ammonium chloride, 15N-sodium nitrate, 15N-urea, 15N-l-alanine in culture
      medium to characterize the biosynthesis of 15N-anatoxin-a (ATX-A), which is a
      major algal toxin from A. flos-aquae, through liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The results showed that all these four types of nitrogen
      can be incorporated into algal cells. The ATX-A production with urea as the
      nitrogen source was much higher than that with the other three types of nitrogen.
      The 15N labeling experiments further demonstrated that the uptake of organic
      nitrogen nutrients was significantly greater than that of inorganic nitrogen.
      These results provide new evidence and deeper insight to explore the biosynthesis
      of ATX-A in the specific strain of A. flos-aquae.

PMID- 29055828
TI  - Microbial activity influences electrical conductivity of biofilm anode.
AB  - This study assessed the conductivity of a Geobacter-enriched biofilm anode in a
      microbial electrochemical cell (MxC) equipped with two gold anodes (25 mM acetate
      medium), as different proton gradients were built throughout the biofilm. There
      was no pH gradient across the biofilm anode at 100 mM phosphate buffer (current
      density 2.38 A/m2) and biofilm conductivity (Kbio) was as high as 0.87 mS/cm. In
      comparison, an inner biofilm became acidic at 2.5 mM phosphate buffer in which
      dead cells were accumulated at ~80 MUm of the inner biofilm anode. At this low
      phosphate buffer, Kbio significantly decreased by 0.27 mS/cm, together with
      declined current density of 0.64 A/m2. This work demonstrates that biofilm
      conductivity depends on the composition of live and dead cells in the conductive
      biofilm anode.

PMID- 29055829
TI  - Density and distribution of nitrifying guilds in rapid sand filters for drinking
      water production: Dominance of Nitrospira spp.
AB  - We investigated the density and distribution of total bacteria, canonical Ammonia
      Oxidizing Bacteria (AOB) (Nitrosomonas plus Nitrosospira), Ammonia Oxidizing
      Archaea (AOA), as well as Nitrobacter and Nitrospira in rapid sand filters used
      for groundwater treatment. To investigate the spatial distribution of these
      guilds, filter material was sampled at four drinking water treatment plants
      (DWTPs) in parallel filters of the pre- and after-filtration stages at different
      locations and depths. The target guilds were quantified by qPCR targeting 16S
      rRNA and amoA genes. Total bacterial densities (ignoring 16S rRNA gene copy
      number variation) were high and ranged from 109 to 1010 per gram (1015 to 1016
      per m3) of filter material. All examined guilds, except AOA, were stratified at
      only one of the four DWTPs. Densities varied spatially within filter (intra
      filter variation) at two of the DWTPs and in parallel filters (inter-filter
      variation) at one of the DWTPs. Variation analysis revealed random sampling as
      the most efficient strategy to yield accurate mean density estimates, with
      collection of at least 7 samples suggested to obtain an acceptable (below half
      order of magnitude) density precision. Nitrospira was consistently the most
      dominant guild (5-10% of total community), and was generally up to 4 orders of
      magnitude more abundant than Nitrobacter and up to 2 orders of magnitude more
      abundant than canonical AOBs. These results, supplemented with further analysis
      of the previously reported diversity of Nitrospira in the studied DWTPs based on
      16S rRNA and nxrB gene phylogeny (Gulay et al., 2016; Palomo et al., 2016),
      indicate that the high Nitrospira abundance is due to their comammox (complete
      ammonia oxidation) physiology. AOA densities were lower than AOB densities,
      except in the highly stratified filters, where they were of similar abundance. In
      conclusion, rapid sand filters are microbially dense, with varying degrees of
      spatial heterogeneity, which requires replicate sampling for a sufficiently
      precise determination of total microbial community and specific population
      densities. A consistently high Nitrospira to bacterial and archaeal AOB density
      ratio suggests that non-canonical pathways for nitrification may dominate the
      examined RSFs.

PMID- 29055830
TI  - Pharmacological inhibition of tankyrase induces bone loss in mice by increasing
      osteoclastogenesis.
AB  - Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and
      degradation of target proteins. Since tankyrase inhibitors suppress the
      degradation of AXIN protein, a negative regulator of the canonical Wnt pathway,
      they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are
      being investigated as drug candidates for cancer and fibrotic diseases, in which
      the Wnt pathways are aberrantly activated. Tankyrase is also reported to degrade
      the adaptor protein SH3BP2 (SH3 domain-binding protein 2). We have previously
      shown that SH3BP2 gain-of-function mutation enhances receptor activator of
      nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis in murine bone
      marrow-derived macrophages (BMMs). Although the interaction between tankyrase and
      SH3BP2 has been reported, it is not clear whether and how the inhibition of
      tankyrase affects bone cells and bone mass. Here, we have demonstrated that
      tankyrase inhibitors (IWR-1, XAV939, and G007-LK) enhanced RANKL-induced
      osteoclast formation and function in murine BMMs and human peripheral blood
      mononuclear cells through the accumulation of SH3BP2, subsequent phosphorylation
      of SYK, and nuclear translocation of NFATc1. Tankyrase inhibitors also enhanced
      osteoblast differentiation and maturation, represented by increased expression of
      osteoblast-associated genes accompanied by the accumulation of SH3BP2 protein and
      enhanced nuclear translocation of ABL, TAZ, and Runx2 in primary osteoblasts.
      Most importantly, pharmacological inhibition of tankyrase in mice significantly
      decreased tibia and lumbar vertebrae bone volumes in association with increased
      numbers of osteoclasts. Our findings uncover the role of tankyrase inhibition in
      bone cells and highlight the potential adverse effects of the inhibitor on bone.

PMID- 29055832
TI  - Fast, highly selective and sensitive anionic metal-organic framework with
      nitrogen-rich sites fluorescent chemosensor for nitro explosives detection.
AB  - Developing a highly efficient fluorescent sensor for detection of trace amounts
      of nitro explosives remains a great challenge. Porous metal-organic frameworks
      (MOFs) are one class of promising fluorescent sensors towards small molecules.
      Herein, we constructed an anionic Zn-based MOF FJI-C8 based on pi-conjugated
      aromatic ligand H6TDPAT (2,4,6-tris(3,5-dicarboxylphenylamino)-1,3,5-triazine)
      containing nitrogen-rich sites. On account of the high density of uncoordinated N
      atoms, the high overlap between the emission spectrum of the anionic MOF FJI-C8
      and the UV-vis absorption spectrum of the representative nitro explosive 2,4
      dinitrophenol (2,4-DNP), and the porosity of the MOF, FJI-C8 is demonstrated to
      be an excellent chemosensor for 2,4-DNP with fast response time (less than 30s),
      high selectivity (Ksv=5.11*104M-1 for 2,4-DNP), extra sensitivity (LOD=0.002866mM
      for 2,4-DNP), low usage amount (0.04mg/mL), good stability and quantitative
      detection features. To the best of our knowledge, this is the first example for
      highly selective detection of 2,4-DNP. More importantly, theoretical calculation
      and control experiments unveiled that the energy transfer is the main mechanism
      for highly detection of 2,4-DNP. This work will pave the way for designing highly
      efficient luminescent chemosensors.

PMID- 29055831
TI  - Cause-specific stillbirth and exposure to chemical constituents and sources of
      fine particulate matter.
AB  - The stillbirth rate in the United States is relatively high, but limited evidence
      is available linking stillbirth with fine particulate matter (PM2.5), its
      chemical constituents and sources. In this study, we explored associations
      between cause-specific stillbirth and prenatal exposures to those pollutants with
      using live birth and stillbirth records from eight California locations during
      2002-2009. ICD-10 codes were used to identify cause of stillbirth from stillbirth
      records. PM2.5 total mass and chemical constituents were collected from ambient
      monitors and PM2.5 sources were quantified using Positive Matrix Factorization.
      Conditional logistic regression was applied using a nested case-control study
      design (N = 32,262). We found that different causes of stillbirth were associated
      with different PM2.5 sources and/or chemical constituents. For stillbirths due to
      fetal growth, the odds ratio (OR) per interquartile range increase in gestational
      age-adjusted exposure to PM2.5 total mass was 1.23 (95% confidence interval (CI):
      1.06, 1.44). Similar associations were found with resuspended soil (OR=1.25, 95%
      CI: 1.10, 1.42), and secondary ammonium sulfate (OR=1.45, 95% CI: 1.18, 1.78). No
      associations were found between any pollutants and stillbirths caused by maternal
      complications. This study highlighted the importance of investigating cause
      specific stillbirth and the differential toxicity levels of specific PM2.5
      sources and chemical constituents.

PMID- 29055833
TI  - Comprehensive analysis of transcriptional and proteomic profiling reveals silver
      nanoparticles-induced toxicity to bacterial denitrification.
AB  - Although the toxicity of silver nanoparticles (Ag NPs or nanosilver) to model
      bacteria has been reported, the effects of Ag NPs on microbial denitrification
      under anoxic conditions and the mechanism of Ag NPs induced-toxicity to
      denitrification remain unclear. In this study, the effects of Ag NPs on
      Paracoccus denitrificans under anoxic conditions were investigated, and the
      mechanism was explored by analyzing the transcriptional and proteomic responses
      of bacteria to Ag NPs. The presence of 5mg/L Ag NPs led to excessive nitrate
      accumulation (232.5 versus 5.3mg/L) and increased nitrous oxide emission.
      Transcriptional analysis indicated that Ag NPs restrained the expression of key
      genes related to denitrification. Specifically, the genes involved in
      denitrifying catalytic reduction and electron transfer were significantly down
      regulated. Moreover, the expression of the genes responsible for
      polyhydroxybutyrate synthesis was enhanced, which was adverse to denitrification.
      Proteomic profiling revealed that the syntheses of the proteins involved in
      catalytic process, electron transfer, and metabolic process were inhibited by Ag
      NPs. The activities of nitrate reductase and nitrite reductase in the presence of
      5mg/L Ag NPs were only 42% and 61% of those in the control, respectively,
      indicating the inhibition of denitrifying enzymes. These results improve
      understanding of the inhibitory mechanism of Ag NPs toward bacterial
      denitrification.

PMID- 29055834
TI  - Long-term industrial metal contamination unexpectedly shaped diversity and
      activity response of sediment microbiome.
AB  - Metal contamination poses serious biotoxicity and bioaccumulation issues,
      affecting both abiotic conditions and biological activity in ecosystem trophic
      levels, especially sediments. The MetalEurop foundry released metals directly
      into the French river "la Deule" during a century, contaminating sediments with a
      30-fold increase compared to upstream unpolluted areas (Ferin, Sensee canal).
      Previous metaproteogenomic work revealed phylogenetically analogous, but
      functionally different microbial communities between the two locations. However,
      their potential activity status in situ remains unknown. The present study
      respectively compares the structures of both total and active fractions of
      sediment prokaryotic microbiomes by coupling DNA and RNA-based sequencing
      approaches at the polluted MetalEurop site and its upstream control. We applied
      the innovative ecological concept of Functional Response Groups (FRGs) to
      decipher the adaptive tolerance range of the communities through characterization
      of microbial lifestyles and strategists. The complementing use of DNA and RNA
      sequencing revealed indications that metals selected for mechanisms such as
      microbial facilitation via "public-good" providing bacteria, Horizontal Gene
      Transfer (HGT) and community coalescence, overall resulting in an unexpected
      higher microbial diversity at the polluted site.

PMID- 29055835
TI  - Preoperative severe hypoalbuminemia is associated with an increased risk of
      postoperative delirium in elderly patients: Results of a secondary analysis.
AB  - PURPOSE: To explore the association between the severity of preoperative
      hypoalbuminemia and the occurrence of postoperative delirium. MATERIALS AND
      METHODS: This was a secondary analysis of the database from a previously
      conducted clinical trial. 700 elderly patients (age >=65years) who were admitted
      to intensive care unit (ICU) after noncardiac surgery were included. Delirium was
      assessed with the Confusion Assessment Method for the ICU twice daily during the
      first 7days postoperatively. Other outcomes were also monitored. The relationship
      between preoperative albumin level and postoperative delirium were analyzed using
      a logistic regression model. RESULTS: 111 of 700 patients (15.9%) developed
      postoperative delirium. When compared with normal albumin level (>40.0g/L),
      severe (<=30.0g/L: OR 2.727, 95% CI 1.283-5.797, P=0.009), but not mild (35.1
      40.0g/L: OR 1.175, 95% CI 0.679-2.032, P=0.565) or moderate (30.1-35.0g/L: OR
      1.674, 95% CI 0.897-3.122, P=0.105) hypoalbuminemia was associated with an
      increased risk of postoperative delirium. Preoperative severe hypoalbuminemia was
      also associated with prolonged mechanical ventilation, increased non-delirium
      complications, and prolonged ICU and hospital stay after surgery. CONCLUSIONS:
      Preoperative severe hypoalbuminemia (<=30.0g/L) was associated with an increased
      risk of postoperative delirium and worse outcomes. TRIAL REGISTRATION: Chinese
      Clinical Trial Registry, www.chictr.org.cn, ChiCTR-TRC-10000802.

PMID- 29055836
TI  - Assessment of PSMA targeting ligands bearing novel chelates with application to
      theranostics: Stability and complexation kinetics of 68Ga3+, 111In3+, 177Lu3+ and
      225Ac3.
AB  - INTRODUCTION: Recent successes in the treatment of metastatic castration
      resistant prostate cancer (mCRPCa) by systemic endoradiotherapy has sparked
      renewed interest in developing small molecule ligands targeting prostate-specific
      membrane antigen (PSMA) and chelators capable of stable complexation of metal
      radionuclides for imaging and therapy. As the size and coordination number of
      metals for imaging, such as 68Ga3+, and for targeted therapy, such as 177Lu3+ and
      225Ac3+, are substantially different, they may show a preference for macrocycles
      of different denticity. We have prepared three simple conjugates that target PSMA
      and form radiometal complexes through coordination by either octa-, deca-, or
      dodecadentate tetraazacyclododecane chelators. The complex formation and metal
      ion selectivity of these constructs were determined at two relevant temperatures,
      complex stability was examined in vitro, and tumor targeting was demonstrated in
      preclinical PCa models with a view towards identifying a candidate with potential
      value as a theranostic agent for the imaging and therapy of mCRPCa. METHODS:
      Three bifunctional chelates with high denticity, including the octadentate
      chelate DOTA, the decadentate 3p-C-DEPA and a novel dodecadentate analogue of
      DEPA, were synthesized and conjugated to a glutamate-urea-lysine (EuK)
      pharmacophore (EuK-DOTA, EuK-107 and EuK-106, respectively) to enable targeting
      of PSMA. The metal ion selectivity for each construct was determined by
      incubation at 25  degrees C and 95  degrees C with the trivalent radiometals
      68Ga3+, 111In3+, 177Lu3+ and 225Ac3+. PSMA binding affinity was determined by
      competitive binding using LNCaP cells, while in vivo tumor targeting of the 68Ga
      labeled constructs was examined by positron emission tomography (PET) in LNCaP
      xenograft tumor-bearing mice. RESULTS: PMSA affinities (IC50 values) were 13.3 +/
      0.9 nM for EuK-DOTA, 18.0 +/- 3.7 nM for EuK-107 and 42.6 +/- 6.6 nM for EuK
      106. EuK-107 and EuK-DOTA proved to rapidly and near quantitatively complex
      68Ga3+, 111In3+, 177Lu3+ and 225Ac3+ at 95  degrees C, with EuK-107 also rapidly
      complexing 111In3+ and 177Lu3+ at 25  degrees C. The inability of EuK-106 to
      chelate 177Lu3+ and 225Ac3+ suggests that size of the cavity of the macrocylic
      ring may be more critical than the number of donor groups for the chelation of
      larger radiometals. In vivo, 68Ga-EuK-107 proved to have similar uptake to 68Ga
      DKFZ-PSMA-617, a theranostic ligand currently in clinical evaluation, in a PSMA
      positive xenograft tumor model. CONCLUSIONS: The broad metal ion selectivity,
      good in vitro affinity for PSMA and good in vivo tumor targeting suggest that EuK
      107, with the 3p-C-DEPA chelator, merits further evaluation as a theranostics
      construct in prostate cancer.

PMID- 29055837
TI  - Removal of the pesticide tebuconazole in constructed wetlands: Design comparison,
      influencing factors and modelling.
AB  - Constructed wetlands (CWs) are a promising technology to treat pesticide
      contaminated water, but its implementation is impeded by lack of data to optimize
      designs and operating factors. Unsaturated and saturated CW designs were used to
      compare the removal of triazole pesticide, tebuconazole, in unplanted mesocosms
      and mesocosms planted with five different plant species: Typha latifolia,
      Phragmites australis, Iris pseudacorus, Juncus effusus and Berula erecta.
      Tebuconazole removal efficiencies were significantly higher in unsaturated CWs
      than saturated CWs, showing for the first time the potential of unsaturated CWs
      to treat tebuconazole contaminated water. An artificial neural network model was
      demonstrated to provide more accurate predictions of tebuconazole removal than
      the traditional linear regression model. Also, tebuconazole removal could be
      fitted an area-based first order kinetics model in both CW designs. The removal
      rate constants were consistently higher in unsaturated CWs (range of 2.6-10.9 cm
      d-1) than in saturated CWs (range of 1.7-7.9 cm d-1) and higher in planted CWs
      (range of 3.1-10.9 cm d-1) than in unplanted CWs (range of 1.7-2.6 cm d-1) for
      both designs. The low levels of sorption of tebuconazole to the substrate (0.7
      2.1%) and plant phytoaccumulation (2.5-12.1%) indicate that the major removal
      pathways were biodegradation and metabolization inside the plants after plant
      uptake. The main factors influencing tebuconazole removal in the studied systems
      were system design, hydraulic loading rate and plant presence. Moreover,
      tebuconazole removal was positively correlated to dissolved oxygen and all
      nutrients removal.

PMID- 29055838
TI  - Chemical composition and source-apportionment of sub-micron particles during
      wintertime over Northern India: New insights on influence of fog-processing.
AB  - A comprehensive study was carried out from central part of Indo-Gangetic Plain
      (IGP; at Kanpur) to understand abundance, temporal variability, processes
      (secondary formation and fog-processing) and source-apportionment of PM1-bound
      species (PM1: particulate matter of aerodynamic diameter <= 1.0 MUm) during
      wintertime. A total of 50 PM1 samples were collected of which 33 samples
      represent submicron aerosol characteristics under non-foggy condition whereas 17
      samples represent characteristics under thick foggy condition. PM1 mass
      concentration during non-foggy episodes varied from 24-393 (Avg.: 247) MUg m-3,
      whereas during foggy condition it ranged from 42-243 (Avg.: 107) MUg m-3. With
      respect to non-foggy condition, the foggy conditions were associated with higher
      contribution of PM1-bound organic matter (OM, by 23%). However, lower fractional
      contribution of SO42-, NO3- and NH4+ during foggy conditions is attributable to
      wet-scavenging owing to their high affinity to water. Significant influence of
      fog-processing on organic aerosols composition is also reflected by co
      enhancement in OC/EC and WSOC/OC ratio during foggy condition. A reduction by 5%
      in mineral dust fraction under foggy condition is associated with a parallel
      decrease in PM1 mass concentration. However, mass fraction of elemental carbon
      (EC) looks quite similar (~3% of PM1) but the mass absorption efficiency (MAE) of
      EC is higher by 30% during foggy episodes. Thus, it is evident from this study
      that fog-processing leads to quite significant enhancement in OM (23%)
      contribution (and MAE of EC) with nearly equal and parallel decrease in SO42-,
      NO3- and NH4+ and mineral dust fractions (totaling to 24%). Characteristic
      features of mineral dust remain similar under foggy and non-foggy conditions;
      inferred from similar ratios of Fe/Al (~0.3), Ca/Al (0.35) and Mg/Al (0.22).
      Positive matrix factorization (PMF) resolves seven sources: biomass burning
      (19.4%), coal combustion (1.1%), vehicular emission (3%), industrial activities
      (6.1%), leather tanneries (4%), secondary transformations (46.2%) and mineral
      dust (20.2%).

PMID- 29055839
TI  - First-in-man phase I study assessing the safety and pharmacokinetics of a 1-hour
      intravenous infusion of the doxorubicin prodrug DTS-201 every 3 weeks in patients
      with advanced or metastatic solid tumours.
AB  - PURPOSE: DTS-201 is a doxorubicin (Dox) prodrug that shows encouraging data in
      experimental models in terms of both efficacy and safety compared with
      conventional Dox. The purpose of this phase I study was to assess the safety
      profile, to establish the recommended dose (RD) for clinical phase II studies and
      to assess potential anticancer activity of the compound. EXPERIMENTAL DESIGN: DTS
      201 was administered as a 1-hour infusion every 3 weeks in eligible patients with
      advanced solid tumours according to common clinical phase I criteria. Dose
      escalation was performed according to a modified Fibonacci schema. RESULTS:
      Twenty-five patients with a median age of 58 years (range, 30-72) were enrolled
      in the study. The median number of treatment cycles was 2 (range, 1-8). DTS-201
      was administered at four dose levels (DLs) ranging from 80 to 400 mg/m2, which is
      equivalent to 45-225 mg/m2 of conventional Dox. No dose-limiting toxicity (DLT)
      occurred at the first two DLs. Three DLTs were observed at DL3 and DL4 (diarrhoea
      for DL3, vomiting and neutropenia for DL4). DL4 (400 mg/m2) was considered the
      maximum tolerated dose. Myelosuppression was the main toxicity, and NCI-CTC grade
      III-IV neutropenia was common at RD. Non-haematological adverse reactions were
      mild to moderate and included nausea, anorexia, asthenia and alopecia. No
      treatment-related severe cardiac adverse events were observed. CONCLUSIONS: DTS
      201 is well tolerated and safe in heavily pretreated solid tumour patients. A
      high equivalent dose of Dox could be delivered without severe drug-related
      cardiac events. DTS-201 showed evidence of clinical activity with a confirmed
      partial response in a patient with soft-tissue sarcoma. The recommended phase II
      dose is 400 mg/m2.

PMID- 29055841
TI  - Response rate as a potential surrogate for survival and efficacy in patients
      treated with novel immune checkpoint inhibitors: A meta-regression of randomised
      prospective studies.
AB  - INTRODUCTION: To assess the role of the tumour response rate (RR) after immune
      checkpoint inhibitors-based therapy as a potential surrogate end-point of
      progression-free survival (PFS) and overall survival (OS) in patients with solid
      tumours, we performed a trial-based meta-regression of randomised studies
      comparing different immune checkpoint inhibitors-based treatments. METHODS: The
      systematic literature search included the electronic databases and the
      proceedings of oncologic meetings. Treatment effects on PFS and OS were expressed
      as hazard ratios (HRs); treatment effects on RR were expressed as odds ratios
      (ORs). A weighted regression analysis was performed on log-transformed treatment
      effect estimates to test the association between treatment effects on the
      surrogate outcome and treatment effects on the clinical outcome. RESULTS: Twenty
      four trials, for a total of 11,894 patients, were included in the analysis. Using
      the complete set of data, the regression of either the log(HR) for PFS or the
      log(HR) for OS on the log(OR) for RR demonstrated weak associations (R2 = 0.47;
      95% confidence interval [CI], 0.03-0.77; P = 0.001; and R2 = 0.32; 95% CI, 0.02
      0.76; P = 0.01, respectively). The pre-planned analyses stratifying trials
      according to different type of disease and different mechanism of action of
      immune checkpoint inhibitors showed a very weak association of the RR with the OS
      for non-small cell lung cancer indicated and a modest association of the RR with
      the PFS for cytotoxic T lymphocyte-associated antigen 4 checkpoint inhibitors.
      CONCLUSION: The results of the trial-based meta-regression analysis indicated a
      weak correlation between RR and OS, supporting future investigations to assess
      the surrogacy of RR in the patient treated with immune checkpoint inhibitors.

PMID- 29055840
TI  - Cytomegalovirus reactivation in patients with refractory checkpoint inhibitor
      induced colitis.
AB  - OBJECTIVES: Immune checkpoint inhibitors can cause severe immune-related adverse
      events, with immune-related diarrhea and colitis (irColitis) being among the most
      frequent ones. While the majority of patients with irColitis respond well to
      corticosteroid treatment +/- other immunomodulatory drugs such as infliximab,
      some patients do not show resolution of their symptoms. In the present study, we
      analysed the frequency of therapy-refractory irColitis, the underlying cause, and
      useful diagnostic approaches. METHODS: Between 2006 and 2016, 370 patients with
      metastatic malignant melanoma were treated with checkpoint inhibitors at the
      Department of Dermatology at the University Hospital Essen. All patients were
      identified for whom diarrhea and/or colitis was documented in the digital patient
      records. Patients who did not respond to standard immunosuppressive therapy
      within 2 weeks were classified as refractory. Demographic and clinical data of
      all patients were collected. RESULTS: We identified 41 patients with irColitis,
      the majority occurring during treatment with ipilimumab. Amongst these, 5 (12.2%)
      were refractory to standard immunomodulatory treatment with corticosteroids and
      infliximab. Therapy-refractory cases tended to show more severe inflammation in
      colonic biopsies (p = 0.04). In all therapy-refractory cases cytomegalovirus
      (CMV) was detectable. CMV-DNA in colonic biopsies and in plasma was significantly
      more often detectable in therapy-refractory cases (in colonic biopsies p = 0.005,
      in plasma: p = 0.002). Presence of serum CMV IgM and positive immunohistochemical
      stainings of colon biopsies for CMV were also associated with refractory colitis
      (p=0.021; p = 0.053). CONCLUSIONS: This report on CMV reactivation during
      management of checkpoint inhibitor-induced colitis emphasises the need for
      repetitive diagnostic measures in treatment-refractory irColitis.

PMID- 29055843
TI  - Revisiting the definition of dose-limiting toxicities in paediatric oncology
      phase I clinical trials: An analysis from the Innovative Therapies for Children
      with Cancer Consortium.
AB  - BACKGROUND: Dose-escalation trials aim to identify the maximum tolerated dose
      and, importantly, the recommended phase II dose (RP2D) and rely on the occurrence
      of dose-limiting toxicities (DLTs) during the first treatment cycle. Molecularly
      targeted agents (MTAs) often follow continuous and prolonged administrations,
      displaying a distinct toxicity profile compared to conventional
      chemotherapeutics, and classical DLT criteria might not be appropriate to
      evaluate MTAs' toxicity. We investigated this issue in children. METHODS: The
      Innovative Therapies for Children with Cancer Consortium (ITCC) phase I trials of
      novel anticancer agents between 2004 and 2015 were analysed. Data from
      investigational product, trial design, items defining DLT/RP2D were extracted. A
      survey on dose-escalation process, DLTs and RP2D definition was conducted among
      the ITCC clinical trials committee members. RESULTS: Thirteen phase I trials with
      15 dose-escalation cohorts were analysed. They explored 11 MTAs and 2 novel
      cytotoxics; 12 evaluated DLT during cycle 1. Definition of DLT was heterogeneous:
      Grade III-IV haematologic toxicities that were transient or asymptomatic and
      grade III-IV non-haematological toxicities manageable with adequate supportive
      care were often excluded, whereas some included dose intensity or grade II
      toxicities into DLT. None of the studies considered delayed toxicity into the
      RP2D definition. CONCLUSION: DLTs should be homogeneously defined across trials,
      limiting the number of exceptions due to specific toxicities. Dose escalation
      should still be based on safety data from cycle 1, but delayed and overall
      toxicities, pharmacokinetic parameters and pharmacodynamic data should be
      considered to refine the final RP2D. The evaluation of long-term toxicity in the
      developing child cannot be adequately addressed in early trials.

PMID- 29055844
TI  - Annual traffic noise levels estimation based on temporal stratification.
AB  - This paper proposes a temporal sampling strategy that increases the accuracy of
      long-term noise level estimation and allows to establish the estimation error
      according to the number of sampled days. Days of the week are stratified into
      working days and weekend days. This research shows how to use measurements of Leq
      on working days to estimate the corresponding values for weekend days. This is
      possible because working days have higher noise levels and less variability than
      weekend days. The improvement in accuracy allows for a reduction in the number of
      required sampled days compared to taking samples randomly, which would help to
      reduce the uncertainty in environmental noise assessment. As a reference, to
      obtain a 90% confidence interval of +/-1 dB for Lday, the proposed sampling
      strategy reduces the required measurement days by more than 38%. For LDEN, the
      reduction is close to 18% of the total number of days. The proposed strategy
      could be adapted to different environments by simply changing a few parameters.

PMID- 29055842
TI  - Clinical and molecular characterisation of hereditary and sporadic metastatic
      colorectal cancers harbouring microsatellite instability/DNA mismatch repair
      deficiency.
AB  - BACKGROUND: Patients treated with chemotherapy for microsatellite unstable (MSI)
      and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer
      (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of
      distinguishing sporadic from Lynch syndrome (LS)-like mCRCs. PATIENTS AND
      METHODS: MSI/dMMR mCRC patients were retrospectively identified in six French
      hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1
      methylation. Sporadic cases were molecularly defined as those displaying
      MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no
      MMR germline mutation. RESULTS: Among 129 MSI/dMMR mCRC patients, 81 (63%) were
      LS-like and 48 (37%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would
      have been misclassified using an algorithm based on local medical records (age,
      Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a
      systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate
      analysis, parameters associated with better overall survival were age (P <
      0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not
      BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and
      metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival,
      but not LS. LS-like patients were associated with more frequent liver
      involvement, metastatic resection and better disease-free survival after
      metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first
      line chemotherapy was similar between the two groups (4.2 and 4.2 months; P =
      0.44). CONCLUSIONS: LS-like and sporadic MSI/dMMR mCRCs display distinct natural
      histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to
      differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular
      whether immune checkpoint inhibitors efficacy differs in these two populations.

PMID- 29055845
TI  - Deriving suitability factors for CA-Markov land use simulation model based on
      local historical data.
AB  - Multiple Criteria Evaluation (MCE) is a multi-attributes decision making tool
      often used in land suitability analysis and land use simulation using Cellular
      Automata (CA)-Markov model. The goal of this research is to explore the
      feasibility of using historical data of a study area to select, score, and weight
      factors quantitatively in the MCE. We have developed logistic regression models
      fitted by the historical land use changes to select and score each potential
      factor, and used the Entropy method to determine weights for the selected
      factors. The MCE output is then used as the input of CA-Markov model to simulate
      land use changes from 2001 to 2011. The land use simulation result was compared
      against observed 2011 land use in order to examine the performance of the updated
      MCE method. The result shows that the use of MCE factors derived from historical
      data produces reasonable goodness of fit, based on current literature. The major
      advantage of the updated MCE method is that the factor selection, scores, and
      weights are all derived from local data reflecting the actual historical trend.
      This quantitative approach also allows one to efficiently calibrate CA-Markov
      model and develop different land use planning scenarios by adjusting scores and
      weights for different factors with the knowledge of historical change.

PMID- 29055846
TI  - The equatorial rainforest of Central Africa between economic needs and
      sustainability requirements.
AB  - This article sets out to investigate the role played by the rainforest of Central
      Africa in providing environmental goods and services, regulating and stabilizing
      the global climate as well as participating in socio-economic development of the
      riparian countries. This complex role offers a double status, almost
      confrontational, to this rainforest: it stands as an economic resource and as a
      major global climate regulator. Hence, there is an urgent need to question
      certain aspects such as climate trends in this strategic region and the use of
      local forest resources for economic purpose in order to suggest ecological
      attitudes to be adopted by policymakers, stakeholders, forest professionals and
      users for a sustainable development. It is shown that: 1) this rainforest
      constitutes an economic resource and plays a major socio-cultural role in
      addition to its global climate regulatory role, 2) an overexploitation of the
      forest resources for economic purposes exposes the forest to an increased
      deterioration which can change the ecological and socio-economic balance, or
      destroy this forest, and by so doing, alter its global climate control power, 3)
      the climate of the region is experiencing serious variability. Thus, solutions
      that can satisfy socio-economic needs and give room for sustainable development
      are proposed.

PMID- 29055847
TI  - Environmental benefit analysis of strategies for potable water savings in
      residential buildings.
AB  - The objective of this study is to assess the environmental benefit of using
      rainwater, greywater, water-efficient appliances and their combinations in low
      income houses. The study was conducted surveying twenty households located in
      southern Brazil, which resulted in water end-uses estimation. Then, embodied
      energy, potential for potable water savings and sewage reduction when using the
      different strategies were estimated. The environmental benefit analysis of these
      strategies was performed using an indicator that includes embodied energy,
      potable water savings, reduction of sewage and energy consumption in the water
      utility, and sewage production during the life cycle of the system. The results
      indicated that the strategy with the greatest environmental benefit is the use of
      water-efficient appliances, which resulted in substantial water savings and
      reduction of sewage, causing low environmental impact due to lower embodied
      energy over the life cycle.

PMID- 29055848
TI  - Modeling the Economic Value of Blue Carbon in Delaware Estuary Wetlands: Historic
      Estimates and Future Projections.
AB  - Coastal wetlands sequester large amounts of carbon in their soils, effectively
      removing carbon dioxide from the atmosphere and acting as a carbon sink. In this
      paper, we estimate the economic value of carbon sequestered by wetlands in the
      Delaware Estuary. We estimate the value of the current stock of wetlands, the
      value of the historic loss of wetlands, and under a range of different scenarios
      the expected future loss. We use historical topographic maps and Land Cover
      inventories of the Delaware Estuary to measure the acreage of tidal wetlands in
      nine distinct time periods from 1778 to 2011. Using these data, we estimate an
      annual rate of wetland loss of 1.03 km2. Coupling observed land cover change with
      exogenous factors including sea-level rise, population pressure, and channel
      dredging, we estimate changes in tidal wetland area under a range of future
      scenarios for our expected future economic loss estimates.

PMID- 29055849
TI  - Field data analysis of active chlorine-containing stormwater samples.
AB  - Many municipalities in Canada and all over the world use chloramination for
      drinking water secondary disinfection to avoid DBPs formation from conventional
      chlorination. However, the long-lasting monochloramine (NH2Cl) disinfectant can
      pose a significant risk to aquatic life through its introduction into municipal
      storm sewer systems and thus fresh water sources by residential, commercial, and
      industrial water uses. To establish general total active chlorine (TAC)
      concentrations in discharges from storm sewers, the TAC concentration was
      measured in stormwater samples in Edmonton, Alberta, Canada, during the summers
      of 2015 and 2016 under both dry and wet weather conditions. The field-sampling
      results showed TAC concentration variations from 0.02 to 0.77 mg/L in summer
      2015, which exceeds the discharge effluent limit of 0.02 mg/L. As compared to
      2015, the TAC concentrations were significantly lower during the summer 2016 (0
      0.24 mg/L), for which it is believed that the higher precipitation during summer
      2016 reduced outdoor tap water uses. Since many other cities also use chloramines
      as disinfectants for drinking water disinfection, the TAC analysis from Edmonton
      may prove useful for other regions as well. Other physicochemical and biological
      characteristics of stormwater and storm sewer biofilm samples were also analyzed,
      and no significant difference was found during these two years. Higher density of
      AOB and NOB detected in the storm sewer biofilm of residential areas - as
      compared with other areas - generally correlated to high concentrations of
      ammonium and nitrite in this region in both of the two years, and they may have
      contributed to the TAC decay in the storm sewers. The NH2Cl decay laboratory
      experiments illustrate that dissolved organic carbon (DOC) concentration is the
      dominant factor in determining the NH2Cl decay rate in stormwater samples. The
      high DOC concentrations detected from a downstream industrial sampling location
      may contribute to a high stormwater NH2Cl decay rate in this area.

PMID- 29055850
TI  - In vitro uptake and metabolism of [14C]acetate in rabbit atherosclerotic
      arteries: biological basis for atherosclerosis imaging with [11C]acetate.
AB  - INTRODUCTION: Detection of vulnerable plaques is critically important for the
      selection of appropriate treatment and/or the prevention of atherosclerosis and
      ensuing cardiovascular diseases. In order to clarify the utility of [11C]acetate
      for atherosclerosis imaging, we determined the uptake and metabolism of acetate
      by in vitro studies using rabbit atherosclerotic arteries and [14C]acetate.
      METHODS: Rabbits were fed with a conventional (n=5) or a 0.5% cholesterol diet
      (n=6). One side of the iliac-femoral arteries was injured by a balloon catheter.
      Radioactivity levels in the iliac-femoral arteries were measured after incubation
      in DMEM containing [1-14C]acetate for 60 min (% dpm/mg tissue). Radioactive
      components in the homogenized arteries were partitioned into aqueous, organic,
      and residue fractions by the Folch method, and analyzed by thin-layer
      chromatography (TLC). RESULTS: The radioactivity level in the injured arteries of
      rabbits fed with the 0.5% cholesterol diet (atherosclerotic arteries) was
      significantly higher than that in either the non-injured or injured arteries of
      rabbits fed with the conventional diet (p<0.05) (% dpm/mg tissue: conventional
      diet groups; 0.022+/-0.005 and 0.024+/-0.007, cholesterol diet groups; 0.029+/
      0.007 and 0.034+/-0.005 for non-injured and injured arteries). In metabolite
      analysis, most of the radioactivity was found in the aqueous fraction in each
      group (87.4-94.6% of total radioactivity in the arteries), and glutamate was a
      dominant component (67.4-69.7% of the aqueous fraction in the arteries).
      CONCLUSIONS: The level of [14C]acetate-derived radioactivity into the arteries
      was increased by balloon injury and the burden of a cholesterol diet. Water
      soluble metabolites were the dominant components with radioactivity in the
      atherosclerotic lesions. These results provide a biological basis for imaging
      atherosclerotic lesions by PET using [11C]acetate.

PMID- 29055851
TI  - Effects of finishing diets containing wet distillers grains plus solubles on beef
      quality attributes and fatty acid profile.
AB  - The objective of this study was to evaluate the effects of feeding wet distillers
      grains plus solubles (WDGS) on quality attributes of three beef muscles
      (longissimus lumborum, psoas major, and infraspinatus). Ninety-six, yearlings
      crossbred steers were randomly assigned to one of three dietary treatments (Corn,
      15%, or 30% WDGS - DM basis) and fed for 133 d. No significant differences were
      observed in marbling score (P=0.89), marbling texture (P=0.70), and marbling
      distribution (P=0.36). Greater concentrations of PUFA and lower levels of 18:1(n
      7) were observed in beef from steers fed 30% WDGS when compared to other
      treatments. Lipid oxidation was also greater in beef from steers fed 30% WDGS
      (P<=0.05). No significant differences were observed in sensorial attributes and
      Warner-Bratzler shear force (WBSF) for all muscles (P>0.05). Feeding WDGS
      increased PUFA and lipid oxidation, which may lead to shorter shelf life.

PMID- 29055852
TI  - Skin care for healthy babies at term: A systematic review of the evidence.
AB  - OBJECTIVES: to identify what skin practices are important for the protection of
      baby skin in healthy term babies (0-6 months) and generate evidence-based
      conclusions to inform health professionals and parents. DESIGN: eleven databases
      were searched for all empirical quantitative and qualitative research published
      between 2000-2015 which explored baby skin care for bathing and cleansing, nappy
      care, hair and scalp care, management of dry skin or baby massage, for healthy
      term babies up to 6 months old. Papers not published in English were excluded. A
      total of 3062 papers were identified. Pairs of reviewers assessed all citations
      and extracted data independently. There were 26 included papers: 16 RCTs, 3 non
      randomised experimental studies, 1 mixed-methods study and 6 qualitative studies.
      Primary and secondary outcome measures were analysed using meta-analysis or
      narrative descriptive statistics. Synthesis of qualitative data was not possible
      due to disparity of the evidence. FINDINGS: from the small numbers of studies
      with comparable data, there was no evidence of any significant differences
      between tested wash products and water or tested baby wipes and water. There was
      some evidence to suggest that daily use of full-body emollient therapy may help
      to reduce the risk of atopic eczema in high risk babies with a genetic
      predisposition to eczema; however, the use of olive oil or sunflower oil for baby
      dry skin may adversely affect skin barrier function. There was no evidence about
      hair/scalp care or baby massage. Qualitative research indicates that parents and
      health professionals believe that water alone is best. KEY CONCLUSIONS: meta
      analysis was restricted due to the lack of consistency of study outcome measures.
      Although there is considerable RCT evidence comparing the use of specific
      products against water alone, or another product, for bathing, cleansing and
      nappy care, the power of this evidence is reduced due to inconsistency of outcome
      measures in terms of outcome, treatment site or time-point. The development of a
      core outcome measure set is advocated for trials assessing skin care practices.
      IMPLICATIONS FOR PRACTICE: this review offers health professionals best evidence
      available on which to base their advice. Of those studies with comparative
      outcomes, the evidence indicates no difference between the specific products
      tested and water alone; offering parents a choice in their baby skin care
      regimen. Protocol available:
      http://www.crd.york.ac.uk/PROSPEROFILES/28054_PROTOCOL_20151009.pdf.

PMID- 29055853
TI  - Morphology and phylogeny of Ameson portunus n. sp. (Microsporidia) infecting the
      swimming crab Portunus trituberculatus from China.
AB  - Ameson portunus n. sp. is a new microsporidian species that infects the skeletal
      muscle of Portunus trituberculatus, a pond-reared swimming crab from China. This
      parasite was characterized using morphological and molecular phylogenetic data.
      Light and transmission electron microscopy revealed that this microsporidian
      experienced disporogonic and polysporogonic (chain-like) life cycles. Mature
      uninucleate spores appeared ovoid, measured 1.4+/-0.06*1.0+/-0.07MUm on ultrathin
      sections, and exhibited no dimorphism. The isofilar polar filament was coiled in
      8-9 turns. Of these coils, 5-9 were arranged in large regular outer layers; the
      remaining coils (0-3 coils) were situated internally. According to phylogenetic
      analyses based on the small subunit (SSU) rDNA gene, A. portunus n. sp. belonged
      to the group comprising Ameson spp. and Nadelspora canceri. The result of
      comprehensive analysis of ultrastructural features, molecular phylogenetic data,
      host and geographical differences among known species supports the establishment
      of a new Ameson species for this parasite. Ameson portunus n. sp. is the first
      Ameson species described from the coasts of East Asia.

PMID- 29055854
TI  - Perceptions of Socratic and non-Socratic presentation of information in cognitive
      behaviour therapy.
AB  - Socratic Method is a style of inquiry used in cognitive behavioural therapy (CBT)
      that encourages clients to reflect on their problems and draw conclusions from
      newly-gained insights. However, assumptions about the superior efficacy of
      Socratic Method over non-Socratic (didactic) approaches remain largely untested.
      The aim of this study was to compare the perceived helpfulness of therapists'
      questions, autonomy supportiveness, likelihood of engaging in therapeutic tasks
      and preference for Socratic Method versus a didactic approach using a video
      analogue and ratings of lay observers. The mediating effects of therapeutic
      alliance and empathy were also examined. Participants (N = 144, mean age = 37, SD
      = 13) completed an online survey where they rated two videoed therapy analogues.
      Socratic Method had higher mean scores on perceived helpfulness of therapists'
      questions, autonomy supportiveness, and likelihood of engaging in therapeutic
      tasks and preference than didactic presentation. Perceived helpfulness and
      preference ratings were higher for Socratic Method after accounting for potential
      confounders. Perceived therapeutic alliance and empathy both mediated the effect
      of therapy condition on autonomy and engagement. The findings support the use of
      Socratic Method in CBT.

PMID- 29055856
TI  - Physiological, biochemical and molecular responses of Mentha aquatica L. to
      manganese.
AB  - Mentha aquatica is an aromatic herb which possesses valuable terpenoids
      constituents. Here, we intended to evaluate the effects of the different
      manganese (Mn) concentrations on the physiological, biochemical and molecular
      responses in M. aquatica. Basic Hoagland's solution (control), 40, 80, and 160
      MUM of Mn supplied as MnSO4.H2O were applied to the nutrient solution. The
      results indicated that the different concentrations of Mn differently affected
      the physiological, biochemical and molecular responses in M. aquatica. The growth
      parameters (biomass and photosynthetic pigments) and expression levels of beta
      caryophyllene synthase (CPS), limonene synthase (Ls), geranyl diphosphate
      synthase (Gpps), and menthofuran synthase (Mfs) genes were increased at the
      moderate Mn concentrations (40 and 80 MUM) and began to decrease at the higher
      levels. However, the contents of anthocyanins, flavonoids, malonaldehyde (MDA)
      and hydrogen peroxide (H2O2), Mn accumulation, activities of antioxidant enzymes,
      yield of essential oils and the expression levels of 1-Deoxy d-xylulose-5
      phosphate synthase (Dxs) and isopentenyl diphosphate isomerase (Ippi) genes were
      gradually increased with increasing concentration of Mn in the nutrient solution.
      Also, the content and chemical composition of terpenoid constituents were altered
      in the Mn-treated plants. Here, we suggest that the application of external Mn in
      nutrient solution elevates the growth and expression levels of the genes that are
      involved in the terpenoid biosynthesis pathway in M. aquatica. Nevertheless, the
      extent and stability of these growth and gene expression elevation are varied
      among the different Mn treatments.

PMID- 29055855
TI  - An island apart? Risks and prices in the Australian cryptomarket drug trade.
AB  - BACKGROUND: Australia has a reputation as an anomaly with regard to cryptomarket
      drug trading, with seemingly disproportionately high levels of activity given its
      relatively small size, high prices and anecdotal accounts of it being a
      destination where many foreign-based vendors will not sell. This paper aims to
      investigate these claims from a risk and prices perspective. METHODS: By
      analysing data for over 60,000 drug products available for purchase from eight
      cryptomarkets in January 2016 this work builds a descriptive picture of the
      Australian online market in comparison to the rest of the world, before moving
      onto analyse the prices of drugs available to Australian consumers, both online
      and though conventional drug supply routes. RESULTS: Results show that the
      Australian online illicit drugs market is of considerable size, internally
      isolated and with methamphetamine sales being particularly large by comparison to
      other countries. Australian cryptomarket vendors sell drugs at significantly
      higher prices than those listed by their foreign counterparts. Online prices are
      however broadly comparable to street prices, with the exception of
      methamphetamine where prices appear to be much lower online. CONCLUSIONS: These
      findings indicate that the perceived stringency of Australian border protection
      inadvertently increases the competitiveness and local market share of domestic
      cryptomarket vendors via a consumer side 'risk tariff', challenging the
      traditionally vendor-oriented drugs risk and prices framework.

PMID- 29055857
TI  - Coumarinyl pyranopyrimidines as new neuropeptide S receptor antagonists; design,
      synthesis, homology and molecular docking.
AB  - In this work, we described the design, synthesis and characterization of a new
      class of NPSR antagonists bearing the tetracyclic coumarinyl pyranopyrimidine
      scaffold incorporated with different acyclic and/or heterocyclic moieties. These
      compounds are highlighted in this study as never being used as NPSR antagonists
      before which provides a model for the discovery of new bioactive inhibitors that
      may hold potential for drug development towards anxiety, food, and addiction
      disorders. Synthetic and medicinal chemistry studies led to the identification of
      four potent antagonists, compounds 7d, 10, 12 and 13, which were able to
      significantly inhibit the stimulatory effect of NPS through counteracting the
      increased intracellular Ca2+ accumulation. The target compound 7d was the most
      active derivative behaving as a pure NPSR antagonist and displaying IC50 value of
      2 MUM. Homology model of NPSR was built based on bovine rhodopsin structure.
      Modeling studies were carried out to further rationalize the NPSR binding mode of
      the target compounds. Moreover, molecular dynamics simulation study was performed
      for compounds 7d, 10 and 12 which revealed the stability of the ligand-protein
      complex and the reliability of the docking studies.

PMID- 29055858
TI  - Deletion of the transcriptional regulator GntR down regulated the expression of
      Genes Related to Virulence and Conferred Protection against Wild-Type Brucella
      Challenge in BALB/c Mice.
AB  - Brucellosis, which is caused by Brucella spp., is a zoonotic infectious disease
      that can cause great hazard to public health and safety. The virulence of
      Brucella is essential for survive and multiply in host macrophages. GntR is a
      transcriptional regulator in Brucella that is required for virulence in
      macrophages and mice, and involved in resistance to stress responses. To
      determine the expression levels of target genes of GntR, we detected the
      expression levels of the GntR target genes in Brucella infected BALB/c mice. The
      results showed that several genes related to virulence, including omp25, virB1,
      vjbR, dnaK, htrA and hfq, were regulated by GntR during infection in BALB/c mice.
      Moreover, the 2308DeltagntR mutant induced high protective immunity in BALB/c
      mice challenge with B. abortus 2308 (S2308), and elicited an anti-Brucella
      specific immunoglobulin G (IgG) response and induced the secretion of gamma
      interferon (IFN-gamma) and interleukin-4 (IL-4). All together, these results
      indicated that gntR promoted the virulence of Brucella. The 2308DeltagntR was
      significantly attenuated in macrophages and mice and induced protective immune
      response during infection, suggested that 2308DeltagntR mutant is an attractive
      candidate for the design of a live attenuated vaccine against Brucella.

PMID- 29055859
TI  - Flavins mediate extracellular electron transfer in Gram-positive Bacillus
      megaterium strain LLD-1.
AB  - The extracellular electron transfer (EET) mechanism of an isolated Gram-positive
      Bacillus megaterium strain (LLD-1), identified by 16S rRNA gene sequencing and
      physiological analysis, was investigated in the present study. The
      electrochemical activity of strain LLD-1 was confirmed by electrochemical E-t and
      amperometric I-t tests. Flavins in culture suspension from strain LLD-1 were
      further proved to be able to act as electron shuttles, strengthening the electron
      transfer from LLD-1 to the electrode. The output voltage and current output were
      increased 2.8 times and 3.7 times, respectively, by adding 100nM exogenetic
      flavins into microbial fuel cells inoculated with LLD-1. Electricity generation
      by LLD-1 from different carbon sources can be enhanced by adding 100nM exogenetic
      flavins. This study indicated that flavins were essential to the EET process of
      the Gram-positive strain LLD-1. Furthermore, a putative EET model for B.
      megaterium strain LLD-1 and even for Gram-positive bacteria was proposed.

PMID- 29055860
TI  - Effects of mould on electrochemical migration behaviour of immersion silver
      finished printed circuit board.
AB  - The role played by mould in the electrochemical migration (ECM) behaviour of an
      immersion silver finished printed circuit board (PCB-ImAg) under a direct current
      (DC) bias was investigated. An interesting phenomenon is found whereby mould,
      especially Aspergillus niger, can preferentially grow well on PCB-ImAg under
      electrical bias and then bridge integrated circuits and form a migration path.
      The cooperation of the mould and DC bias aggravates the ECM process occurring on
      PCB-ImAg. When the bias voltage is below 15V, ECM almost does not occur for Ag
      coating. Mechanisms that explain the ECM processes of PCB-ImAg in the presence of
      mould and DC bias are proposed.

PMID- 29055861
TI  - Internal validation of the RapidHIT(r) ID system.
AB  - Traditionally, forensic DNA analysis has required highly skilled forensic
      geneticists in a dedicated laboratory to generate short tandem repeat (STR)
      profiles. STR profiles are routinely used either to associate or exclude
      potential donors of forensic biological evidence. The typing of forensic
      reference samples has become more demanding, especially with the requirement in
      some jurisdictions to DNA profile arrestees. The Rapid DNA (RDNA) platform, the
      RapidHIT(r) ID (IntegenX(r), Pleasanton, CA), is a fully automated system capable
      of processing reference samples in approximately 90min with minimal human
      intervention. Thus, the RapidHIT ID instrument can be deployed to non-laboratory
      environments (e.g., booking stations) and run by trained atypical personnel such
      as law enforcement. In order to implement the RapidHIT ID platform, validation
      studies are needed to define the performance and limitations of the system.
      Internal validation studies were undertaken with four early-production RapidHIT
      ID units. Reliable and concordant STR profiles were obtained from reference
      buccal swabs. Throughout the study, no contamination was observed. The overall
      first-pass success rate with an "expert-like system" was 72%, which is comparable
      to another current RDNA platform commercially available. The system's second-pass
      success rate (involving manual interpretation on first-pass inconclusive results)
      increased to 90%. Inhibitors (i.e., coffee, smoking tobacco, and chewing tobacco)
      did not appear to affect typing by the instrument system; however, substrate
      (i.e., swab type) did impact typing success. Additionally, one desirable feature
      not available with other Rapid systems is that in the event of a system failed
      run, a swab can be recovered and subsequently re-analyzed in a new sample
      cartridge. Therefore, rarely should additional sampling or swab consumption be
      necessary. The RapidHIT ID system is a robust and reliable tool capable of
      generating complete STR profiles within the forensic DNA typing laboratory or
      with proper training in decentralized environments by non-laboratory personnel.

PMID- 29055862
TI  - Juvenile exposure to bisphenol A promotes ovarian differentiation but suppresses
      its growth - Potential involvement of pituitary follicle-stimulating hormone.
AB  - Bisphenol A (BPA), a plastic monomer and plasticizer, is commonly used in
      plastics industry, and it has been well documented to be an estrogenic endocrine
      disrupter. In the present study, we investigated the effect of early (juvenile)
      exposure to BPA on the hypothalamic-pituitary-gonad (HPG) axis in the zebrafish.
      Estradiol (E2) and testosterone (T) were also included as positive and negative
      controls respectively. Juvenile zebrafish were exposed to BPA (1 and 10MUM), E2
      (10nM) and T (10nM) from 20 to 40 dpf (days post-fertilization), the period of
      sex/gonadal differentiation, followed by histological and expression analyses at
      40 dpf. The ovary and hepatic proteomes were also analyzed by mass spectrometry.
      Our results showed that 20day exposure to BPA and E2 increased the ratio of
      females; however, they both significantly suppressed ovarian growth. Meanwhile,
      BPA and E2 significantly suppressed fshb but stimulated lhb expression in the
      pituitary. These effects did not seem to involve the hypothalamus because neither
      BPA nor E2 altered the expression of kiss1, kiss2, gnrh2 and gnrh3 in the
      hypothalamus. At the ovary level, BPA and E2 both decreased lhcgr expression.
      Interestingly, E2 and BPA displayed different effects in the liver. E2 induced a
      significant hepatic hypertrophy; however, BPA had no such effect. Analysis of
      hepatic proteomes revealed distinct protein profiles in the E2 group as compared
      with the others, especially fructose-bisphospahte aldolase B. These results
      indicated that BPA has estrogenic effects on female reproduction, but it does not
      mimic all E2 actions. Our data in the zebrafish suggest that sex differentiation
      involves estrogens and it is a sensitive window for evaluating estrogenic
      activities of compounds and their impacts on wildlife reproduction.

PMID- 29055863
TI  - Synthesis and characterization of biogenic metal nanoparticles and its
      cytotoxicity and anti-neoplasticity through the induction of oxidative stress,
      mitochondrial dysfunction and apoptosis.
AB  - In the present study, we demonstrate a simple, cost-effective and eco-friendly
      method for biogenic synthesis of silver nanoparticles (AgNPCGs) using ethanolic
      extract of Calotropis gigantea latex. Attempts were made to characterize these
      biogenic silver nanoparticles AgNPCGs and also to test its cytotoxic, anti
      neoplastic and apoptotic potential through the induction of oxidative stress,
      mitochondrial dysfunction. AgNPCGs were characterized by UV-vis spectroscopy,
      dynamic light scattering (DLS) and surface zeta potential measurement, Fourier
      transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission
      electron microscopy (TEM) and selected area electron diffraction, scanning
      electron microscopy (SEM), energy-dispersive X-ray fluorescence spectrometry
      (EDX). UV visible spectroscopy showed an intense surface plasmon resonance band
      at 431nm which clearly reflected the formation of silver nanoparticles. FTIR
      study revealed that latex extract acted as reducing and stabilizing agent for the
      synthesis of AgNPCGs. Energy dispersive X-ray spectroscopy confirmed the presence
      of silver as a major component of synthesized AgNPCGs. SEM and TEM studies showed
      that the synthesized AgNPCGs were nearly spherical in shape with an average size
      of 2.338nm. The selected area electron diffraction pattern and XRD studies
      confirmed the crystalline nature of AgNPCGs. AgNPCGs exhibited in-vitro cytotoxic
      activity against Ehrlich's ascites carcinoma (EAC), Jurkat and MCF-7 cells at
      respective IC50 doses without producing cytotoxicity to mice and human
      lymphocytes. Significant chromatin condensation, DNA fragmentation, cell cycle
      arrest at G2/M phase, up-regulation of Bax and caspase-3 and down-regulation of
      Bcl-2 were observed in AgNPCGs treated EAC cells. The results suggest that
      biogenic silver nanoparticles AgNPCGs could be a potential chemotherapeutic
      formulation for cancer therapy.

PMID- 29055864
TI  - Microemulsion formulation design and evaluation for hydrophobic compound:
      Catechin topical application.
AB  - The aim of the present study was to design a microemulsion for catechin topical
      application. A mixture experimental design with five independent variables (X1:
      oil, X2: surfactant, X3: catechin, X4: cosurfactant and X5: water) was developed,
      and the response surface methodology was used to study the effect of formulation
      components on physiochemical characteristics and penetration capacity of a
      catechin-loaded microemulsion, and to obtain an optimal microemulsion
      formulation. The results showed that the drug-loaded microemulsion formation and
      characteristics were related to many parameters of the components. The
      transdermal amounts in receiver cells and skin deposition amount remarkably
      increased about 4.1-111.6-fold and 0.6-7.6-fold respectively. The lag time was
      significantly shortened from 10h to 1.0-6.7h. The optimal formulation with 20%
      surfactant, 30% cosurfactant and 2.6% Catechin was subjected to stability and
      irritation tests. The results showed that the physicochemical characteristics and
      catechin level of the drug-loaded microemulsion did not show significant
      degradation after 3 months of storage at 25 degrees C.The catechin-loaded
      microemulsion did not cause significant irritation compared to the water-treated
      group.

PMID- 29055865
TI  - Injectable deferoxamine nanoparticles loaded chitosan-hyaluronic acid coacervate
      hydrogel for therapeutic angiogenesis.
AB  - In this study, an injectable chitosan-hyaluronic acid (CS-HA) based hydrogel was
      designed incorporating pro-angiogenic molecule, deferoxamine loaded PLGA
      nanoparticles (DFO NPs), for enhancing angiogenesis. DFO-NPs were prepared by
      double emulsion solvent diffusion technique and characterized for their
      physicochemical properties. The DLS and SEM analysis showed an average particle
      size of 220+/-71nm with spherical morphology and the encapsulation efficiency was
      found to be 30+/-5%. An ECM mimicking chitosan-hyaluronic acid (CS-HA) coacervate
      hydrogel was prepared. Both free DFO and DFO NPs were entrapped into the prepared
      CS-HA composite hydrogel. The hydrogels were characterized by SEM, FTIR and
      Rheology. Addition of DFO NPs did not affect the injectablility and flowability
      of developed hydrogels. In vitro DFO release from the prepared composite
      hydrogels showed controlled release over a period of 10days. Both the hydrogel
      systems showed excellent cyto-compatability and good cell proliferation for rASCs
      as well as HUVECs. The DFO and DFO NPs loaded composite hydrogels revealed
      effective tube formation in comparison with control hydrogels without DFO and DFO
      NPs. The in vivo angiogenic evaluation of the free DFO and DFO NPs (0.025%w/w)
      loaded composite hydrogels were studied by injecting the developed hydrogel
      subcutaneously into mice for 2-4 weeks. The DFO NPs loaded composite hydrogel had
      enhanced neovascularization when compared to control gels. Thus, the developed
      DFO NPs loaded composite hydrogel could potentially be used for therapeutic
      angiogenesis.

PMID- 29055866
TI  - High diversity of human parechovirus including novel types in stool samples from
      Ghanaian children.
AB  - BACKGROUND: Little is known on human parechovirus (HPeV) infections in Africa.
      OBJECTIVES: We aimed to determine the prevalence, genetic diversity, and
      association with diarrhea of HPeV in Ghanaian children. STUDY DESIGN: A total of
      682 stool samples from a pediatric case-control study on causes of diarrhea
      collected in 2007-2008 were used. Laboratory analysis included HPeV real-time RT
      PCR and sequencing partial viral protein (VP) 1 gene region of HPeV. In addition,
      data on co-infections using the xTAG Gastrointestinal Pathogen Panel were
      available. RESULTS: Overall, a prevalence of 24% was found and 14 different HPeV
      types were detected. Phylogenetic analysis of the VP1 region indicated a novel
      type tentatively designated as HPeV-18. No association with diarrhea was found
      (OR=0.8; 95% CI: 0.5-1.1), and HPeV viral concentrations were not different among
      cases and controls. No seasonal pattern was observed. HPeV-positive cases
      displayed a slightly higher chance of co-infections. CONCLUSIONS: A high
      prevalence and genetic diversity of HPeV including novel types was found by
      sequencing partial VP 1 region. HPeV was not associated with diarrheal disease in
      this pediatric population and the high number of co-infection suggests transient
      colonization without clinical relevance.

PMID- 29055867
TI  - Pre-surgical mapping of eloquent cortex for paediatric epilepsy surgery
      candidates: Evidence from a review of advanced functional neuroimaging.
AB  - PURPOSE: A review of all published evidence for mapping eloquent (motor, language
      and memory) cortex using advanced functional neuroimaging (functional magnetic
      resonance imaging [fMRI] and magnetoencephalography [MEG]) for paediatric
      epilepsy surgery candidates has not been conducted previously. Research in this
      area has predominantly been in adult populations and applicability of these
      techniques to paediatric populations is less established. METHODS: A review was
      performed using an advanced systematic search and retrieval of all published
      papers examining the use of functional neuroimaging for paediatric epilepsy
      surgery candidates. RESULTS: Of the 2724 papers retrieved, 34 met the inclusion
      criteria. Total paediatric participants identified were 353 with an age range of
      5 months-19 years. Sample sizes and comparisons with alternative investigations
      to validate techniques are small and variable paradigms are used. Sensitivity
      0.72 (95% CI 0.52-0.86) and specificity 0.60 (95% CI 0.35-0.92) values with a
      Positive Predictive Value of 74% (95% CI 61-87) and a Negative Predictive Value
      of 65% (95% CI 52-78) for fMRI language lateralisation with validation, were
      obtained. Retrieved studies indicate evidence that both fMRI and MEG are able to
      provide information lateralising and localising motor and language functions.
      CONCLUSIONS: A striking finding of the review is the paucity of studies (n=34)
      focusing on the paediatric epilepsy surgery population. For children, it remains
      unclear which language and memory paradigms produce optimal activation and how
      these should be quantified in a statistically robust manner. Consensus needs to
      be achieved for statistical analyses and the uniformity and yield of language,
      motor and memory paradigms. Larger scale studies are required to produce patient
      series data which clinicians may refer to interpret results objectively. If
      functional imaging techniques are to be the viable alternative for pre-surgical
      mapping of eloquent cortex for children, paradigms and analyses demonstrating
      concordance with independent measures must be developed.

PMID- 29055868
TI  - Rescue Medications in Epilepsy Patients: A Family Perspective.
AB  - PURPOSE: The aim of this study was to analyze pre-hospital seizure rescue
      medication (RM) use in a pediatric epilepsy population, caregiver knowledge and
      comfort, and prescription patterns. METHOD: Cross-sectional observational study
      based on surveys to families of pediatric patients with epilepsy and based on
      medical chart review. RESULTS: One hundred (88%) out of 114 families answered the
      questionnaire. Fifty-five patients were females (55%), with a median (IQR) age of
      11 (6-14) years. Eighty-seven (87%) patients had RM prescribed, and 37 (42.5%)
      used it in the past. In univariate analysis, patients were more likely to have a
      RM when they had a history of SE (p<0.001), or had seizures >=30seconds
      (p=0.001). Patients were not more likely to be prescribed a RM if they were
      diagnosed at <2years of age, had >=3 anti-seizure medications (ASM), had a
      history of seizure clusters or uncontrolled epilepsy, or were currently not on
      ASMs. In multivariate analysis a history of SE (p=0.02) and seizure duration
      >=30seconds (p=0.04) remained significant. Out of 91 families, 68 (75%) prefer a
      non-rectal RM; this was higher for patients with normal development, and not
      associated with age or sex. Fifty-three (61%) families reported that they
      received RM training. Ten (12%) parents did not know the RM name, and 31 (36%)
      did not know the administration timing. Forty-five (45%) families had a seizure
      action plan (SAP), and this was a predictor for knowing the RM name (p=0.04), the
      administration timing (p=0.004), availability of RM at school (p=0.02), and
      knowing what to do if the RM fails (p=0.008). CONCLUSIONS: Most patients with
      epilepsy had a RM, but only 61% reported receiving training. Patients were more
      likely to have a RM if they had prior SE and longer seizure duration. Families
      with a SAP were more knowledgeable, and schools were more involved.

PMID- 29055869
TI  - Triazolopyridinyl-acrylonitrile derivatives as antimicrotubule agents: Synthesis,
      in vitro and in silico characterization of antiproliferative activity, inhibition
      of tubulin polymerization and binding thermodynamics.
AB  - In this paper we report the synthesis, in vitro anticancer activity, and the
      experimental/computational characterization of mechanism of action of a new
      series of E isomers of triazolo[4,5-b/c]pyridin-acrylonitrile derivatives (6c-g,
      7d-e, 8d-e, 9c-f, 10d-e, 11d-e). All new compounds are endowed with moderate to
      interesting antiproliferative activity against 9 different cancer cell lines
      derived from solid and hematological human tumors. Fluorescence-based assays
      prove that these molecules interfere with tubulin polymerization. Furthermore,
      isothermal titration calorimetry (ITC) provides full tubulin/compound binding
      thermodynamics, thereby ultimately qualifying and quantifying the interactions of
      these molecular series with the target protein. Lastly, the analysis based on the
      tight coupling of in vitro and in silico modeling of the interactions between
      tubulin and the title compounds allows to propose a molecular rationale for their
      biological activity.

PMID- 29055870
TI  - Fructose-1,6-bisphosphatase inhibitors: A new valid approach for management of
      type 2 diabetes mellitus.
AB  - The rising incidence of diabetes and confines allied with clinical therapies
      emphasized the need to explore new molecular targets to develop novel, effective
      and safer antihyperglycemic agents. Excessive endogenous glucose production by
      gluconeogenesis is a primary determinant of hyperglycemia in patients with type 2
      diabetes. But not even a single current medication acts directly to reduce
      gluconeogenesis. Fructose-1,6-bisphosphatase (FBPase), a well recognized rate
      controlling enzyme of gluconeogenesis, has emerged as legitimate molecular level
      target to control gluconeogenesis mediated glucose overproduction and its
      inhibitors are likely to fulfill an unmet medical need. In this compilation
      various chemical classes of FBPase inhibitors have been reviewed which mainly
      acts through uncompetitive and non-competitive manner. A detailed account on
      structure activity relationship studies of inhibitors have been presented along
      with their molecular level interactions at binding sites of enzyme. Three
      Dimensional Quantitative Structure Activity relationship (3D-QSAR) studies,
      performed to optimize the lead, have been summarized at some places. In this
      assemblage, FBPase inhibitors patented in past have been compiled in tabular
      form. This review highlights the new insight into the therapeutic utility of
      FBPase inhibitors and their potential as a new class of antidiabetic drugs.

PMID- 29055872
TI  - Pollution characteristics and health risk assessment of phthalate esters in urban
      soil in the typical semi-arid city of Xi'an, Northwest China.
AB  - A total of 62 urban soil samples were collected in the city of Xi'an in Northwest
      China, and analyzed for six U.S. Environmental Protection Agency priority
      phthalate esters (PAEs). Unlike earlier studies on PAEs in agricultural soil as
      well as urban soil in humid climates, this paper for the first time
      comprehensively assessed pollution characteristics and health risks of human
      exposure to PAEs in urban soil in a typical semi-arid climate. The total
      concentrations of the six PAEs (Sigma6PAEs) in the urban soil varied between
      193.0 and 19146.4 MUg kg-1 with a mean of 1369.3 MUg kg-1. The PAEs were
      dominated by di-n-butyl phthalate and di(2-ethylhexyl) phthalate. Magnetic
      susceptibility and soil texture were controlling factors influencing the
      concentrations of PAEs in the urban soil. The concentrations of benzyl butyl
      phthalate, di(2-ethylhexyl) phthalate, and Sigma6PAEs increased from the first to
      third ring roads, while the concentrations of di-n-octyl phthalate decreased.
      Relatively higher levels of PAEs were observed in industrial, traffic, and
      residential areas. The PAEs in the urban soil originated mainly from the
      application of plasticizers or additives, use of cosmetics and personal care
      products, emissions of construction materials and home furnishings, industrial
      processes, and atmospheric deposition. The concentrations of some PAEs in the
      urban soil exceeded soil allowable concentrations and environmental risk levels.
      The non-cancer and carcinogenic risks of human exposure to the PAEs were
      relatively low.

PMID- 29055871
TI  - Acute telomerase components depletion triggers oxidative stress as an early event
      previous to telomeric shortening.
AB  - Loss of function of dyskerin (DKC1), NOP10 and TIN2 are responsible for different
      inheritance patterns of Dyskeratosis congenita (DC; ORPHA1775). They are key
      components of telomerase (DKC1 and NOP10) and shelterin (TIN2), and play an
      important role in telomere homeostasis. They participate in several fundamental
      cellular processes by contributing to Dyskeratosis congenita through mechanisms
      that are not fully understood. Presence of oxidative stress was postulated to
      result from telomerase ablation. However, the resulting disturbed redox status
      can promote telomere attrition by generating a vicious circle, which promotes
      cellular senescence. This fact prompted us to study if acute loss of DKC1, NOP10
      and TINF2 can promote redox disequilibrium as an early event when telomere
      shortening has not yet taken place. We generated siRNA-mediated (DKC1, NOP10 and
      TINF2) cell lines by RNA interference, which was confirmed by mRNA and protein
      expression analyses. No telomere shortening occurred in any silenced cell line.
      Depletion of H/ACA ribonucleoproteins DKC1 and NOP10 diminished telomerase
      activity via TERC down-regulation, and produced alterations in pseudouridylation
      and ribosomal biogenesis. An increase in the GSSG/GSH ratio, carbonylated
      proteins and oxidized peroxiredoxin-6 was observed, in addition to MnSOD and TRX1
      overexpression in the siRNA DC cells. Likewise, high PARylation levels and high
      PARP1 protein expression were detected. In contrast, the silenced TINF2 cells did
      not alter any evaluated oxidative stress marker. Altogether these findings lead
      us to conclude that loss of DKC1 and NOP10 functions induces oxidative stress in
      a telomere shortening independent manner.

PMID- 29055874
TI  - SMA-like syndrome with variant mesenteric venous anatomy.
AB  - Superior mesenteric artery (SMA) syndrome refers to the constellation of symptoms
      that are associated with intermittent obstruction of the duodenum due to vascular
      compression. We present a case of SMA-like syndrome related to variant mesenteric
      venous drainage in the setting of normal aortomesenteric angle (AMA) and
      borderline reduced aortomesenteric distance (AMD).

PMID- 29055873
TI  - Ecological risk assessment of trace metals in the surface sediments of the
      Persian Gulf and Gulf of Oman: Evidence from subtropical estuaries of the Iranian
      coastal waters.
AB  - This study aimed to investigate the ecological risk assessment of Khamir, Tiyab,
      and Jagin estuaries and the impact of anthropogenic activities on these
      ecosystems during a one-year study period (April 2015 to March 2016) using trace
      metals as pollution indices. The sediment samples were collected from nine
      sampling stations, following a gradient of contamination from the industrial
      wastewater and shrimp farming effluents to the less impacted stations. Pollution
      indices (i.e. PERI and PLI) were applied to ascertain the sediment quality. Based
      on pollution indices, the overall pattern of environmental quality status
      demonstrated that industrial sewage and shrimp farming effluents are major
      sources of pollution in the Khamir and Tiyab estuaries, respectively. The
      sediments in the most stations in studied coastal ecosystems of Iran posed
      moderate or considerable ecological risk. Results from this study showed that Zn,
      Pb, Cu, and Cd were mostly derived from anthropogenic activities such as domestic
      sewage and industrial effluents. Also, the findings of this study revealed that
      the pollution indices are suitable for evaluating the environmental situation of
      coastal ecosystems and the separation of areas with less impacted by human
      activities from areas affected by these activities and could be used as a robust
      management tool for monitoring programs in coastal areas. Altogether, these
      findings could be useful in providing more effective and targeted strategies of
      development better management practices for coastal areas.

PMID- 29055875
TI  - Stability behaviour of antiretroviral drugs and their combinations. 8:
      Characterization and in-silico toxicity prediction of degradation products of
      efavirenz.
AB  - Efavirenz (EFV), an antiretroviral drug, was evaluated for its degradation
      behaviour in solution state. A total of twelve degradation products were detected
      on high performance liquid chromatography (HPLC) analyses. Initially,
      comprehensive mass fragmentation pattern of the drug was established by direct
      injection and collection of high resolution mass spectrometry (HRMS) and multi
      stage tandem mass spectrometry (MSn) data. Subsequently, LC-HRMS studies were
      carried on the stability samples containing the degradation products. Eleven
      degradation products were isolated and subjected to 1D and 2D nuclear magnetic
      resonance (NMR) studies for their structural confirmation. The collated
      information was utilized for the characterization of all the degradation products
      and hence in outlining the comprehensive degradation pathway of the drug. In
      silico toxicity of the degradation products was evaluated by TOPKAT analyses.

PMID- 29055876
TI  - Umbilical metastasis mimicking symptomatic hernia: Report of a case of Sister
      Mary Joseph Syndrome.
AB  - INTRODUCTION: An umbilical mass can be the first symptom of an intra-abdominal
      neoplasia, and this condition is also defined as Sister Mary Joseph Syndrome.
      CASE PRESENTATION: An eighty-year-old patient presented with a complicated
      umbilical hernia. CT scan abdomen revealed a pancreatic neoplasm and an umbilical
      biopsy confirmed diagnosis of metastasis. Patient started chemotherapy by
      Oncologists. CONCLUSIONS: In this paper the Authors suggest a histopathological
      evaluation of umbilical fat in all cases of newly emerging umbilical hernia in
      the adult population.

PMID- 29055877
TI  - Surgical treatment of locally advanced papillary thyroid carcinoma after response
      to lenvatinib: A case report.
AB  - INTRODUCTION: Differentiated thyroid carcinomas (DTC) have good prognoses after
      complete resection. Nevertheless, when DTC is associated with an aerodigestive
      invasion, curative surgery is difficult to perform. However, there is no
      established neoadjuvant therapy for advanced DTC. PRESENTATION OF CASE: A 73-year
      old man with thyroid papillary carcinoma was referred to our hospital. A computed
      tomography examination revealed a tumor in the upper right lobe of the thyroid,
      and multiple bilateral enlarged lymph nodes in the neck, involving the
      surrounding structures. The enlarged lymph node at the right upper neck was
      suspected to have invaded the right internal jugular vein, and the left
      paratracheal lymph node was suspected to have invaded the cervical esophagus and
      trachea. The tumor was considered resectable; however, surgery would have been
      highly invasive. Therefore, we initiated neoadjuvant therapy with lenvatinib.
      After administration of lenvatinib, the tumor decreased in size by 84.3% and the
      cervical lymph nodes by 56.0%. The patient underwent a total thyroidectomy,
      modified neck dissection, a resection of the muscular layer of the esophagus, and
      a tracheal sleeve resection and reconstruction. DISCUSSION: The SELECT trial
      demonstrated that lenvatinib had high response rate with short response time, in
      patients with radioiodine-refractory DTC. The results suggested that lenvatinib
      could be effective as neoadjuvant therapy. CONCLUSION: For an advanced DTC that
      requires removal through invasive surgery, preoperative lenvatinib treatment
      might be one of the options for a less invasive surgery.

PMID- 29055878
TI  - Laparoscopic hemicolectomy for a patient with situs inversus totalis: A case
      report.
AB  - INTRODUCTION: Situs inversus totalis (SIT) is a rare congenital anomaly in which
      the left and right aspects of the thoracic and intra-abdominal organs are
      inverted, like a mirror image. Surgical procedures in a patients with SIT is
      difficult as their anatomy is abnormal. In particular, laparoscopic procedures
      are considered more difficult in patients with SIT because of the mirror-image
      anatomy. PRESENTATION OF CASE: The patient was a 75-year-old woman with ascending
      colon cancer. Laparoscopic hemicolectomy with radical lymphadenectomy was
      performed. After surgery, no specific complications developed. On the ninth
      postoperative day, the patient was discharged from our hospital. Recognition of
      the inverted anatomy by the surgeon using preoperative imaging permitted safe
      operation using techniques not otherwise differing from those used in ordinary
      cases. DISCUSSION AND CONCLUSIONS: Laparoscopic colectomy is considered to be a
      safe and feasible option for patients with colorectal cancer and SIT.

PMID- 29055879
TI  - Computed tomography fistulography of the sternum. A case report on
      interprofessional collaboration between radiologist and surgeon.
AB  - INTRODUCTION: Trans sternal fistula can occur after sternotomy/heart surgery.
      Diagnosing this can be difficult. PRESENTATION OF CASE: In this report, we
      present a unique case of a patient with infection of an ascending aortic
      prosthetic graft. This patient was oozing from the wound despite several
      revisions. Many fistulographies were performed before fistulography with surgeon
      and radiologist revealed a trans sternal fistula. DISCUSSION: Infection with
      Propionibacterium acnes is often difficult to diagnose. This is in line with the
      present case, where a surgeon guided fistulography had to be performed followed
      by appropriate redo surgery with succesful subsequent sternal wound healing.
      CONCLUSION: Our case demonstrates the importance of performing a fistulography
      with the presence of a surgeon, to obtain the best possible result.

PMID- 29055880
TI  - Component separation of abdominal wall with intraoperative botulinum A presents
      satisfactory outcomes in large incisional hernias: a case report.
AB  - PURPOSE: Transplantation patients have a series of associated risk factors that
      make appearance of incisional hernia (IH) more likely. A number of aspects of the
      closure of large defects remain controversial. In this manuscript, we present the
      repair of a large IH following liver transplantation through the technique of
      posterior components separation combined with the anterior, together with the
      intraoperative use of botulinum toxin A and the placement of mesh. As a secondary
      objective, we analyze the incidence of IH following liver transplantation in our
      service. METHODS: Between the years 2013 and 2016, 247 patients underwent liver
      transplantation in the Liver Transplantation Service at the Hospital das Clinicas
      da Faculdade de Medicina da Universidade de Sao Paulo, Brazil. We analyzed the
      incidence of IH in these patients. One of these cases operated in March 2017
      presented a defect in the abdominal wall of 22*16.6*6.4cm in the median and
      paramedian regions. We present the details of this innovative surgical technique.
      RESULTS: The total operating time was 470min. During the postoperative phase the
      patient presented ileus paralysis, without systemic repercussions. Resumption of
      an oral diet on the fifth postoperative day, without incident. Hospital discharge
      occurred on the 12th postoperative day, with outpatient follow up. CONCLUSION: In
      our service, the incidence of incisional hernias following liver transplantation
      is 14.5%. We described a successful approach for selected patient group for whom
      there is no established standard treatment. Given the complexity of such cases,
      however, more studies are necessary.

PMID- 29055881
TI  - Fitbit Charge HR Wireless Heart Rate Monitor: Validation Study Conducted Under
      Free-Living Conditions.
AB  - BACKGROUND: Many modern smart watches and activity trackers feature an optical
      sensor that estimates the wearer's heart rate. Recent studies have evaluated the
      performance of these consumer devices in the laboratory. OBJECTIVE: The objective
      of our study was to examine the accuracy and sensitivity of a common wrist-worn
      tracker device in measuring heart rates and detecting 1-min bouts of moderate to
      vigorous physical activity (MVPA) under free-living conditions. METHODS: Ten
      healthy volunteers were recruited from a large university in Singapore to
      participate in a limited field test, followed by a month of continuous data
      collection. During the field test, each participant would wear one Fitbit Charge
      HR activity tracker and one Polar H6 heart rate monitor. Fitbit measures were
      accessed at 1-min intervals, while Polar readings were available for 10-s
      intervals. We derived intraclass correlation coefficients (ICCs) for individual
      participants comparing heart rate estimates. We applied Centers for Disease
      Control and Prevention heart rate zone cut-offs to ascertain the sensitivity and
      specificity of Fitbit in identifying 1-min epochs falling into MVPA heart rate
      zone. RESULTS: We collected paired heart rate data for 2509 1-min epochs in 10
      individuals under free-living conditions of 3 to 6 hours. The overall ICC
      comparing 1-min Fitbit measures with average 10-s Polar H6 measures for the same
      epoch was .83 (95% CI .63-.91). On average, the Fitbit tracker underestimated
      heart rate measures by -5.96 bpm (standard error, SE=0.18). At the low intensity
      heart rate zone, the underestimate was smaller at -4.22 bpm (SE=0.15). This
      underestimate grew to -16.2 bpm (SE=0.74) in the MVPA heart rate zone. Fitbit
      devices detected 52.9% (192/363) of MVPA heart rate zone epochs correctly.
      Positive and negative predictive values were 86.1% (192/223) and 92.52%
      (2115/2286), respectively. During subsequent 1 month of continuous data
      collection (270 person-days), only 3.9% of 1-min epochs could be categorized as
      MVPA according to heart rate zones. This measure was affected by decreasing wear
      time and adherence over the period of follow-up. CONCLUSIONS: Under free-living
      conditions, Fitbit trackers are affected by significant systematic errors.
      Improvements in tracker accuracy and sensitivity when measuring MVPA are required
      before they can be considered for use in the context of exercise prescription to
      promote better health.

PMID- 29055882
TI  - Influence of Natural American Spirit advertising on current and former smokers'
      perceptions and intentions.
AB  - OBJECTIVE: This study sought to demonstrate causal effects of exposure to Natural
      American Spirit (NAS) advertising content on misinformed beliefs of current and
      former smokers, and to empirically establish these beliefs as a mechanism driving
      intentions to use NAS. METHODS: Our study employed a randomised experimental
      design with 1128 adult daily, intermittent and former smokers. We compared
      participants who were exposed to NAS advertisements or claims made in the
      advertisements with those in a no-message control group to test the effects of
      NAS advertising content on inaccurate beliefs about NAS and attitudes and
      intentions towards the product. RESULTS: One-way analysis of variance revealed
      that exposure to NAS advertisements produced inaccurate beliefs about the
      composition of NAS cigarettes among current and former smokers (p<0.05). Planned
      contrasts indicated a compilation of arguments taken directly from NAS
      advertisements resulted in significantly greater beliefs that NAS cigarettes are
      healthier/safer than other cigarettes (for former smokers, t(472)=3.63, p<0.001;
      for current smokers, t(644)=2.86, p=0.004), demonstrating that suggestive claims
      used in the brand's marketing have effects on beliefs not directly addressed in
      the advertisements. Regression and mediation analyses showed that health-related
      beliefs predict attitudes towards NAS for current and former smokers, and mediate
      intentions to use NAS. CONCLUSIONS: The findings of this study provide causal
      support for the need for further regulatory action to address the potentially
      harmful ramifications of claims used in NAS advertising.

PMID- 29055883
TI  - Efficacy of a movement control injury prevention programme in adult men's
      community rugby union: a cluster randomised controlled trial.
AB  - BACKGROUND: Exercise programmes aimed at reducing injury have been shown to be
      efficacious for some non-collision sports, but evidence in adult men's collision
      sports such as rugby union is lacking. OBJECTIVE: To evaluate the efficacy of a
      movement control injury prevention exercise programme for reducing match injuries
      in adult men's community rugby union players. METHODS: 856 clubs were invited to
      participate in this prospective cluster randomised (single-blind) controlled
      trial where clubs were the unit of randomisation. 81 volunteered and were
      randomly assigned (intervention/control). A 42-week exercise programme was
      followed throughout the season. The control programme reflected 'normal practice'
      exercises, whereas the intervention focused on proprioception, balance, cutting,
      landing and resistance exercises.Outcome measures were match injury incidence and
      burden for: (1) all >=8 days time-loss injuries and (2) targeted (lower limb,
      shoulder, head and neck, excluding fractures and lacerations) >=8 days time-loss
      injuries. RESULTS: Poisson regression identified no clear effects on overall
      injury outcomes. A likely beneficial difference in targeted injury incidence
      (rate ratio (RR), 90% CI=0.6, 0.4 to 1.0) was identified, with a 40% reduction in
      lower-limb incidence (RR, 90% CI=0.6, 0.4 to 1.0) and a 60% reduction in
      concussion incidence (RR, 90% CI=0.4, 0.2 to 0.7) in the intervention group.
      Comparison between arms for clubs with highest compliance (>=median compliance)
      demonstrated very likely beneficial 60% reductions in targeted injury incidence
      (RR, 90% CI=0.4, 0.2 to 0.8) and targeted injury burden (RR, 90% CI=0.4, 0.2 to
      0.7). CONCLUSIONS: The movement control injury prevention programme resulted in
      likely beneficial reductions in lower-limb injuries and concussion. Higher
      intervention compliance was associated with reduced targeted injury incidence and
      burden.

PMID- 29055884
TI  - Long-term follow-up for cancer incidence in a cohort of Danish firefighters.
AB  - OBJECTIVES: To examine cancer incidence among Danish firefighters using several
      employment-related exposure subgroups. METHODS: A historical cohort of 9061 male
      Danish firefighters was established from collected personnel and membership
      records from employers and trade unions. Using the unique Danish personal
      identification number, information on additional previous employment, cancer and
      vital status was linked to members of the cohort from the Supplementary Pension
      Fund Register, the Danish Cancer Registry and the Danish Civil Registration
      System. SIRs were calculated for specific cancer types using rates for the
      general population, a sample of the working population and military employees,
      respectively. RESULTS: Compared with the selected reference groups, the overall
      observed incidence of cancer among the firefighters was at level with the
      expected (SIR 1.02, 95% CI 0.96 to 1.09 vs the general population). The SIR for
      colon cancer was consistently significantly reduced, while the slight excess seen
      for melanoma of the skin, prostate and testicular cancer compared with the
      general population was not reproduced using the military as reference.
      CONCLUSIONS: Previous associations with melanoma of the skin, prostate and
      testicular cancer are supported by our main results. However, the increase in
      incidence of these cancers is not reproduced using the military as reference.
      Similarities in cancer profile for the firefighters and the military point to
      shared risk factors in either lifestyle or work environment.

PMID- 29055885
TI  - Industrial hog farming is associated with altered circulating immunological
      markers.
AB  - OBJECTIVES: The previously observed inverse association between hog farming and
      risk of lung cancer in the Agricultural Health Study (AHS) has been attributed to
      endotoxin exposure, the levels of which are particularly high in industrial hog
      confinement facilities. We conducted an investigation to explore the potential
      biological mechanisms underlying this association, as well as other immunological
      changes associated with hog farming. METHODS: Serum immune marker levels were
      measured using a multiplexed bead-based assay in 61 active hog farmers and 61
      controls matched on age, phlebotomy date and raising cattle. Both groups
      comprised non-smoking male AHS participants from Iowa. We compared natural log
      transformed marker levels between hog farmers and controls using multivariate
      linear regression models. RESULTS: Circulating levels of macrophage-derived
      chemokine (CCL22), a chemokine previously implicated in lung carcinogenesis, were
      reduced among hog farmers (17% decrease; 95% CI -28% to -4%), in particular for
      those with the largest operations (>6000 hogs: 26% decrease; 95% CI -39% to -10%;
      ptrend=0.002). We also found that hog farmers had elevated levels of other immune
      markers, including macrophage inflammatory protein-3 alpha (MIP-3A/CCL20; 111%
      increase, 95% CI 19% to 273%), basic fibroblast growth factor (FGF-2; 93%
      increase, 95% CI 10% to 240%) and soluble interleukin-4 receptor (12% increase,
      95% CI 1% to 25%), with particularly strong associations for MIP-3A/CCL20 and FGF
      2 in winter. CONCLUSIONS: These results provide insights into potential
      immunomodulatory mechanisms through which endotoxin or other exposures associated
      with hog farming may influence lung cancer risk, and warrant further
      investigation with more detailed bioaerosol exposure assessment.

PMID- 29055886
TI  - Impact of considering non-occupational radiation exposure on the association
      between occupational dose and solid cancer among French nuclear workers.
AB  - OBJECTIVES: The French nuclear worker cohort allows for the assessment of cancer
      risk associated with occupational radiation exposure, but workers are also
      exposed to medical and environmental radiation which can be of the same order of
      magnitude. This study aims to examine the impact of non-occupational radiation
      exposures on the dose-risk analysis between occupational radiation exposure and
      cancer mortality. METHODS: The cohort included workers employed before 1995 for
      at least one year by CEA, AREVA NC or EDF and badge-monitored for external
      radiation exposure. Monitoring results were used to calculate occupational
      individual doses. Scenarios of work-related X-ray and environmental exposures
      were simulated. Poisson regression was used to quantify associations between
      occupational exposure and cancer mortality adjusting for non-occupational
      radiation exposure. RESULTS: The mean cumulative dose of external occupational
      radiation was 18.4 mSv among 59 004 workers. Depending on the hypotheses made,
      the mean cumulative work-related X-ray dose varied between 3.1 and 9.2 mSv and
      the mean cumulative environmental dose was around 130 mSv. The unadjusted excess
      relative rate of cancer per Sievert (ERR/Sv) was 0.34 (90% CI -0.44 to 1.24).
      Adjusting for environmental radiation exposure did not substantially modify this
      risk coefficient, but it was attenuated by medical exposure (ERR/Sv point
      estimate between 0.15 and 0.23). CONCLUSIONS: Occupational radiation risk
      estimates were lower when adjusted for work-related X-ray exposures.
      Environmental exposures had a very slight impact on the occupational exposure
      risk estimates. In any scenario of non-occupational exposure considered, a
      positive but insignificant excess cancer risk associated with occupational
      exposure was observed.

PMID- 29055887
TI  - Response to: 'Does 'job' predict exposure to magnetic fields?' by Sorahan and
      Swanson.

PMID- 29055889
TI  - Response to: 'Pleural abnormalities in the Framingham Heart Study: prevalence and
      CT image features' by Araki et al.

PMID- 29055888
TI  - Prenatal exposure to glycol ethers and cryptorchidism and hypospadias: a nested
      case-control study.
AB  - OBJECTIVES: Glycol ethers (GE) are oxygenated solvents frequently found in
      occupational and consumer products. Some of them are well-known testicular and
      developmental animal toxicants. This study aims to evaluate the risk of male
      genital anomalies in association with prenatal exposure to GE using urinary
      biomarkers of exposure. METHODS: We conducted a case-control study nested in two
      joint mother-child cohorts (5303 pregnant women). Cases of cryptorchidism and
      hypospadias were identified at birth and confirmed during a 2-year follow-up
      period (n=14 cryptorchidism and n=15 hypospadias). Each case was matched to three
      randomly selected controls within the cohorts for region of inclusion and
      gestational age at urine sampling. Concentrations of five GE acidic metabolites
      were measured in spot maternal urine samples collected during pregnancy. ORs were
      estimated with multivariate conditional logistic regressions including a Firth's
      penalisation. RESULTS: Detection rates of urinary GE metabolites ranged from 8%
      to 93% and only two were sufficiently detected (>33%) in each cohort to be
      studied: methoxyacetic acid (MAA) and phenoxyacetic acid (PhAA). A significantly
      higher risk of hypospadias was associated with the highest tertile of exposure to
      MAA: OR (95% CI) 4.5(1.4 to 23.4). No association were observed with urinary
      concentration of PhAA, nor with the risk of cryptorchidism. CONCLUSIONS: In view
      of the toxicological plausibility of our results, this study, despite its small
      sample size, raises concern about the potential developmental toxicity of MAA on
      the male genital system and calls for thorough identification of current sources
      of exposure to MAA.

PMID- 29055890
TI  - Utility of prehospital electrocardiogram characteristics as prognostic markers in
      out-of-hospital pulseless electrical activity arrests.
AB  - BACKGROUND: It is unclear if there are predictors of survival, including ECG
      characteristics, that can guide resuscitative efforts in pulseless electrical
      activity (PEA) cardiac arrests. We studied the predictive potential of presenting
      prehospital ECGs on survival for patients with out-of-hospital cardiac arrest
      (OHCA) with PEA. METHODS: We studied prehospital ECGs of patients with OHCA
      prospectively enrolled between June 2007 and November 2009 at the Ottawa/OPALS
      (Ontario Prehospital Advanced Life Support Study) site of the Resuscitation
      Outcomes Consortium PRIMED study (Prehospital Resuscitation using an IMpedance
      valve and Early versus Delayed analysis). We included adult non-traumatic OHCA
      with PEA rhythm where resuscitation was attempted. We measured HR, QRS interval
      and presence of P waves, and determined their impact on return of spontaneous
      circulation (ROSC) and survival to hospital discharge (SHD) using multivariate
      regression analysis. RESULTS: The demographic characteristics of the 332 included
      cases were the following: mean age 71.8, male 58.4%, SHD 5.4% and ROSC at ED
      arrival 26.5%. Survivors had similar HR (56.8 vs 52.0 beats per minute (bpm),
      p=0.53) and QRS intervals (128.7 vs 129.6 ms, p=0.95) compared with non
      survivors. Prehospital ECG characteristics did not predict SHD or ROSC on
      multivariate analyses. Patients with initial HR <30 bpm had a 3.8% survival rate;
      those with both HR <30 bpm and QRS>=120 ms had a 3.7% survival rate. Location of
      arrest predicted SHD (adjusted OR (AdjOR)=1.49, 1.11 to 1.99; p=0.007). Atropine
      use negatively predicted SHD (AdjOR=0.06, 0.02 to 0.22; p<0.001). Predictors of
      ROSC ALS paramedic on scene (AdjOR=8.90, 1.11 to 71.41; p=0.04) and successful
      intubation (AdjOR=3.35, 1.75 to 6.39; p<0.001). Atropine use negatively predicted
      ROSC (AdjOR=0.27, 0.14 to 0.50; p<0.001). CONCLUSIONS: Presenting prehospital ECG
      characteristics did not predict SHD or ROSC in OHCA PEA victims and should not be
      used to guide termination of resuscitation. Location of arrest was a positive
      predictor for SHD; atropine use was a negative predictor. ALS paramedic on scene
      and successful intubation were positive predictors of ROSC; atropine use was a
      negative predictor. TRIAL REGISTRATION NUMBER: NCT00394706; post-results.

PMID- 29055891
TI  - Using an alumni survey to target improvements in an emergency medicine training
      programme.
AB  - INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) is
      the governing body responsible for accrediting graduate medical training
      programme in the USA. The Emergency Medicine Milestones (EM-Milestones) were
      developed by the ACGME and American Board of Emergency Medicine as a guide and
      monitoring tool for the knowledge, skills, abilities and experiences to be
      acquired during training. Alumni surveys have been reported as a valuable
      resource for training programme to identify areas for improvement; however, there
      are few studies regarding programme improvement in emergency medicine. We aimed
      to use the EM-Milestones, adapted as an alumni self-assessment survey, to
      identify areas for training programme improvement. METHODS: This study was
      conducted at an urban, academic affiliated, community hospital in New York city
      with an emergency medicine training programme consisting of 30 residents over 3
      years. Alumni of our emergency medicine training programme were sent an EM
      Milestones-based self-assessment survey. Participants evaluated their ability in
      each EM-Milestones subcompetency on a Likert scale. Data were analysed using
      descriptive statistics. RESULTS: Response rate was 74% (69/93). Alumni reported
      achieving the target performance in 5/6 general competencies, with Systems-Based
      Practice falling below the target performance. The survey further identified 6/23
      subcompetencies (Pharmacotherapy, Ultrasound, Wound Management, Patient Safety,
      Systems-Based Management and Technology) falling below the target performance
      level. DISCUSSION: Alumni self-evaluation of competence using the EM-Milestones
      provides valuable information concerning confidence to practice independently;
      these data, coupled with regular milestone evaluation of existing trainees, can
      identify problem areas and provide a blueprint for targeted programme
      improvement.

PMID- 29055892
TI  - Perceived support at work after critical incidents and its relation to
      psychological distress: a survey among prehospital providers.
AB  - INTRODUCTION: Prehospital providers are at increased risk for psychological
      distress. Support at work after critical incidents is believed to be important
      for providers, but current guidelines are in need of more scientific evidence.
      This study aimed to investigate: (1) to what extent prehospital providers
      experience support at work; (2) whether support at work is directly associated
      with lower distress and (3) whether availability of a formal peer support system
      is related to lower distress via perceived colleague support. METHODS: This cross
      sectional study surveyed prehospital providers from eight western industrialised
      countries between June and November 2014. A supportive work environment was
      operationalised as perceived management and colleague support (Job Content
      Questionnaire), availability of a formal peer support system and having enough
      time to recover after critical incidents. The outcome variable was psychological
      distress (Kessler 10). We conducted multiple linear regression analyses and
      mediation analysis. RESULTS: Of the 813 respondents, more than half (56.2%) were
      at moderate to high risk of psychological distress. Participants did not
      consistently report support at work (eg, 39.4% were not aware of formal peer
      support). Perceived management support (b (unstandardised regression
      coefficient)=-0.01, 95% CI -0.01 to 0.00), having enough time to recover after
      critical incidents (b=-0.07, 95% CI -0.09 to -0.04) and perceived colleague
      support (b=-0.01, 95% CI -0.01 to 0.00) were related to lower distress.
      Availability of formal peer support was indirectly related to lower distress via
      increased perceived colleague support (beta=-0.04, 95% CI -0.02 to -0.01).
      CONCLUSIONS: Prehospital providers at risk of psychological distress may benefit
      from support from colleagues and management and from having time to recover after
      critical incidents. Formal peer support may assist providers by increasing their
      sense of support from colleagues. These findings need to be verified in a
      longitudinal design.

PMID- 29055893
TI  - Tackling the demand for emergency department services: there are no silver
      bullets.

PMID- 29055894
TI  - Major incident triage and the implementation of a new triage tool, the MPTT-24.
AB  - INTRODUCTION: The Modified Physiological Triage Tool (MPTT) is a recently
      developed primary triage tool and in comparison with existing tools demonstrates
      the greatest sensitivity at predicting need for life-saving intervention (LSI)
      within both military and civilian populations. To improve its applicability, we
      proposed to increase the upper respiratory rate (RR) threshold to 24 breaths per
      minute (bpm) to produce the MPTT-24. Our aim was to conduct a feasibility
      analysis of the proposed MPTT-24, comparing its performance with the existing UK
      Military Sieve. METHOD: A retrospective review of the Joint Theatre Trauma
      Registry (JTTR) and Trauma Audit Research Network (TARN) databases was performed
      for all adult (>18 years) patients presenting between 2006-2013 (JTTR) and 2014
      (TARN). Patients were defined as priority one (P1) if they received one or more
      LSIs. Using first recorded hospital RR in isolation, sensitivity and specificity
      of the >=24 bpm threshold was compared with the existing threshold (>=22 bpm) at
      predicting P1 status. Patients were then categorised as P1 or not-P1 by the MPTT,
      MPTT-24 and the UK Military Sieve. RESULTS: The MPTT and MPTT-24 outperformed
      existing UK methods of triage with a statistically significant (p<0.001) increase
      in sensitivity of between 25.5% and 29.5%. In both populations, the MPTT-24
      demonstrated an absolute reduction in sensitivity with an increase in specificity
      when compared with the MPTT. A statistically significant difference was observed
      between the MPTT and MPTT-24 in the way they categorised TARN and JTTR cases as
      P1 (p<0.001). CONCLUSIONS: When compared with the existing MPTT, the MPTT-24
      allows for a more rapid triage assessment. Both continue to outperform existing
      methods of primary major incident triage and within the military setting, the
      slight increase in undertriage is offset by a reduction in overtriage. We
      recommend that the MPTT-24 be considered as a replacement to the existing UK
      Military Sieve.

PMID- 29055895
TI  - The pattern of paediatric blast injury in Afghanistan.
AB  - INTRODUCTION: Between 2009 and 2015, 3746 children died, and 7904 were injured as
      a result of armed conflict within Afghanistan. Improvised explosive devices
      (IEDs) and explosive remnants of war accounted for 29% of child casualties in
      2015. The aim of this study was to review the burden of paediatric blast injuries
      admitted to Camp Bastion, Afghanistan, and to investigate the hypothesis that
      children suffer proportionally more head injuries than adults. METHOD: A
      retrospective analysis was undertaken of prospectively collected data derived
      from the UK Joint Theatre Trauma Registry of ambulant paediatric (aged 2-15
      years) admissions with blast injuries at the Role 3 Field Hospital, Camp Bastion
      from June 2006 to March 2013. The data set included demographic information,
      injury profile and severity (New Injury Severity Score) and operative findings.
      The pattern of injuries were investigated by looking at trends in the number and
      severity of injuries sustained by each body region. RESULTS: During this period,
      295 admissions were identified, 76% of whom were male, with an overall mortality
      rate of 18.5%. The most common blast mechanism was an IED (68%) causing 80% of
      fatalities. The lower extremities were the most commonly injured body region,
      accounting for 31% of total injuries and occurring in 62% of cases. 24.3% of
      children between 2 and 7 years suffered severe head or neck injuries compared
      with 19.8% of children aged between 8 and 15 years. 34% of head injuries were
      rated unsurvivable and accounted for 88% of fatalities. 77% of cases required an
      operation with a mean operating time of 125 min. The most common first operations
      were debridement of soft tissues (50%), laparotomy (16%) and lower limb
      amputation (11%). CONCLUSION: Although paediatric blast casualties represented a
      small percentage of the overall workload at Camp Bastion Role 3 Medical Facility,
      the pattern of injuries seen suggests that children are more likely to sustain
      severe head, face and neck injuries than adults.

PMID- 29055896
TI  - SIFD as a novel cause of severe fetal hydrops and neonatal anaemia with iron
      loading and marked extramedullary haemopoiesis.
AB  - SIFD describes a heritable, syndromic condition characterised principally by
      sideroblastic anaemia (SA) with immunodeficiency, fevers and developmental delay,
      arising in mutations within the TRNT1 gene. Other clinical manifestations of SIFD
      include cardiomyopathy, seizures, sensorineural hearing loss, renal dysfunction,
      metabolic abnormalities, hepatosplenomegaly and retinitis pigmentosa.Presentation
      of SIFD is variable but typically in early childhood with SA or with fever. In
      this report, we extend the described SIFD phenotype. We describe a kindred in
      which the index case presented with fetal hydrops, and early neonatal death, and
      the second child had severe anaemia at delivery. Both cases had prominent
      extramedullary erythropoiesis and numerous circulating nucleated red blood cells.

PMID- 29055897
TI  - T cell clonality assessment: past, present and future.
AB  - T cell clonality testing has important clinical and research value, providing a
      specific and reproducible assessment of clonal diversity in T cell
      proliferations. Here we review the conceptual foundations of T cell clonality
      assays, including T cell ontogeny and T cell receptor structure and function; we
      also provide an introduction to T cell receptor genomics and the concept of the T
      cell clonotype. This is followed by a review of historical and current methods by
      which T cell clonality may be assayed, including current assay limitations. Some
      of these assay limitations have been overcome by employing next-generation
      sequencing (NGS)-based technologies that are becoming a mainstay of modern
      molecular pathology. In this vein, we provide an introduction to NGS
      technologies, including a review of the preanalytical, analytical and
      postanalytical technologies relevant to T cell clonality NGS assays.

PMID- 29055898
TI  - Night-time communication at Stanford University Hospital: perceptions, reality
      and solutions.
AB  - BACKGROUND: Resident work hour restrictions have led to the creation of the
      'night float' to care for the patients of multiple primary teams after hours.
      These residents are often inundated with acute issues in the numerous patients
      they cover and are less able to address non-urgent issues that arise at night.
      Further, non-urgent pages may contribute to physician alarm fatigue and
      negatively impact patient outcomes. OBJECTIVE: To delineate the burden of non
      urgent paging at night and propose solutions. METHODS: We performed a resident
      review and categorisation of 1820 pages to night floats between September 2014
      and December 2014. Both attending and nursing review of 10% of pages was done and
      compared. RESULTS: Of reviewed pages, 62.1% were urgent and 27.7% were non
      urgent. Attending review of random page samples correlated well with resident
      review. Common reasons for non-urgent pages were non-urgent patient status
      updates, low-priority order requests and non-critical lab values. CONCLUSIONS: A
      significant number of non-urgent pages are sent at night. These pages likely
      distract from acute issues that arise at night and place an unnecessary burden on
      night floats. Both behavioural and systemic adjustments are needed to address
      this issue. Possible interventions include integrating low-priority messaging
      into the electronic health record system and use of charge nurses to help
      determine urgency of issues and batch non-urgent pages.

PMID- 29055900
TI  - Balancing the skills: the need for an improvement pyramid.

PMID- 29055899
TI  - Are quality improvement collaboratives effective? A systematic review.
AB  - BACKGROUND: Quality improvement collaboratives (QIC) have proliferated
      internationally, but there is little empirical evidence for their effectiveness.
      METHOD: We searched Medline, Embase, CINAHL, PsycINFO and the Cochrane Library
      databases from January 1995 to December 2014. Studies were included if they met
      the criteria for a QIC intervention and the Cochrane Effective Practice and
      Organisation of Care (EPOC) minimum study design characteristics for inclusion in
      a review. We assessed study bias using the EPOC checklist and the quality of the
      reported intervention using a subset of SQUIRE 1.0 standards. RESULTS: Of the 220
      studies meeting QIC criteria, 64 met EPOC study design standards for inclusion.
      There were 10 cluster randomised controlled trials, 24 controlled before-after
      studies and 30 interrupted time series studies. QICs encompassed a broad range of
      clinical settings, topics and populations ranging from neonates to the elderly.
      Few reports fully described QIC implementation and methods, intensity of
      activities, degree of site engagement and important contextual factors. By care
      setting, an improvement was reported for one or more of the study's primary
      effect measures in 83% of the studies (32/39 (82%) hospital based, 17/20 (85%)
      ambulatory care, 3/4 nursing home and a sole ambulance QIC). Eight studies
      described persistence of the intervention effect 6 months to 2 years after the
      end of the collaborative. Collaboratives reporting success generally addressed
      relatively straightforward aspects of care, had a strong evidence base and noted
      a clear evidence-practice gap in an accepted clinical pathway or guideline.
      CONCLUSIONS: QICs have been adopted widely as an approach to shared learning and
      improvement in healthcare. Overall, the QICs included in this review reported
      significant improvements in targeted clinical processes and patient outcomes.
      These reports are encouraging, but most be interpreted cautiously since fewer
      than a third met established quality and reporting criteria, and publication bias
      is likely.

PMID- 29055901
TI  - Balancing measures or a balanced accounting of improvement impact: a qualitative
      analysis of individual and focus group interviews with improvement experts in
      Scotland.
AB  - BACKGROUND: As quality improvement (QI) programmes have become progressively
      larger scale, the risks of implementation having unintended consequences are
      increasingly recognised. More routine use of balancing measures to monitor
      unintended consequences has been proposed to evaluate overall effectiveness, but
      in practice published improvement interventions hardly ever report identification
      or measurement of consequences other than intended goals of improvement. METHODS:
      We conducted 15 semistructured interviews and two focus groups with 24
      improvement experts to explore the current understanding of balancing measures in
      QI and inform a more balanced accounting of the overall impact of improvement
      interventions. Data were analysed iteratively using the framework approach.
      RESULTS: Participants described the consequences of improvement in terms of
      desirability/undesirability and the extent to which they were expected/unexpected
      when planning improvement. Four types of consequences were defined: expected
      desirable consequences (goals); expected undesirable consequences (trade-offs);
      unexpected undesirable consequences (unpleasant surprises); and unexpected
      desirable consequences (pleasant surprises). Unexpected consequences were
      considered important but rarely measured in existing programmes, and an
      improvement pause to take stock after implementation would allow these to be more
      actively identified and managed. A balanced accounting of all consequences of
      improvement interventions can facilitate staff engagement and reduce resistance
      to change, but has to be offset against the cost of additional data collection.
      CONCLUSION: Improvement measurement is usually focused on measuring intended
      goals, with minimal use of balancing measures which when used, typically monitor
      trade-offs expected before implementation. This paper proposes that improvers and
      leaders should seek a balanced accounting of all consequences of improvement
      across the life of an improvement programme, including deliberately pausing after
      implementation to identify and quantitatively or qualitatively evaluate any
      pleasant or unpleasant surprises.

PMID- 29055903
TI  - Significant correlation between meibomian gland dysfunction and keratitis in
      young patients with Demodex brevis infestation.
AB  - AIMS: To report the clinical characteristics and correlation between meibomian
      gland dysfunction (MGD) and keratitis in young patients with ocular demodicosis.
      METHODS: Observational case series of 60 patients younger than 35 years with
      ocular demodicosis, of which the diagnosis was based on microscopic counting of
      Demodex folliculorum and D. brevis of epilated lashes. Severity of keratitis and
      MGD was graded by photography and meibography, respectively, in a masked fashion.
      RESULTS: MGD was detected in 54/60 (90%) patients with the loss of meibomian
      gland in the upper lid more than the lower lid (p<0.001). Blepharoconjunctivitis
      and a variety of corneal pathologies were noted in 47/60 (78.3%) and 39/60 (65%)
      patients, respectively. For a total of 120 eyes, normal cornea was noted in 53
      (44.2%) eyes, superficial punctate keratitis or limbitis was noted in 17 (14.2%),
      while corneal stromal infiltration was found in 50 (41.7%) eyes. Both univariate
      and multivariate analyses showed that the severity of meibomian gland loss was
      significantly correlated with higher D. brevis count and more severe keratitis
      (all p<0.05). Rapid resolution of keratitis and blepharoconjunctivitis was
      accompanied by significant reduction of the Demodex count in 48 patients
      receiving lid scrub directed to kill mites. CONCLUSIONS: There is a significant
      correlation between MGD and keratitis in young patients with ocular demodicosis
      especially inflicted by D. brevis.

PMID- 29055902
TI  - LGI1, CASPR2 and related antibodies: a molecular evolution of the phenotypes.
AB  - Recent biochemical observations have helped redefine antigenic components within
      the voltage-gated potassium channel (VGKC) complex. The related autoantibodies
      may be now divided into likely pathogenic entities, which target the
      extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin
      associated protein-like 2 (CASPR2), and species that target intracellular
      neuronal components and are likely non-pathogenic. This distinction has enhanced
      clinical practice as direct determination of LGI1 and CASPR2 antibodies offers
      optimal sensitivity and specificity. In this review, we describe and compare the
      clinical features associated with pathogenic LGI1 and CASPR2 antibodies,
      illustrate emerging laboratory techniques for antibody determination and describe
      the immunological mechanisms that may mediate antibody-induced pathology. We
      highlight marked clinical overlaps between patients with either LGI1 or CASPR2
      antibodies that include frequent focal seizures, prominent amnesia, dysautonomia,
      neuromyotonia and neuropathic pain. Although occurring at differing rates, these
      commonalities are striking and only faciobrachial dystonic seizures reliably
      differentiate these two conditions. Furthermore, the coexistence of both LGI1 and
      CASPR2 antibodies in an individual occurs surprisingly frequently. Patients with
      either antibody respond well to immunotherapies, although systematic studies are
      required to determine the magnitude of the effect beyond placebo. Finally, data
      have suggested that CASPR2 and LGI1 modulation via genetic or autoimmune
      mechanisms may share common intermediate molecules. Taken together, the
      biochemical distinction of antigenic targets has led to important clinical
      advances for patient care. However, the striking syndrome similarities,
      coexistence of two otherwise rare antibodies and molecular insights suggest the
      VGKC complex may yet be a common functional effector of antibody action. Hence,
      we argue for a molecular evolution alongside a clinical and phenotypic re
      evaluation.

PMID- 29055905
TI  - Macular imaging by optical coherence tomography in the diagnosis and management
      of glaucoma.
AB  - The macular area is important to the detection of glaucomatous retinal ganglion
      cell (RGC) damage. Macular thickness complementary to peripapillary retinal nerve
      fibre layer (RNFL) thickness can well reflect glaucomatous damage, given that the
      macula contains more than 50% of the RGCs in a multilayered pattern and larger
      RGC bodies compared with their axons. Thus, macular ganglion cell thickness
      parameters recently have been considered to be an effective glaucoma-diagnostic
      tool comparable to RNFL thickness parameters. Furthermore, spectral-domain
      optical coherence tomography ganglion cell-inner plexiform layer thickness and
      deviation maps can provide additional information essential for distinguishing
      glaucomatous changes from other, myopia-associated or macular disease-associated
      changes. Therefore, our aim with this study was to review the clinical
      application of macular imaging by optical coherence tomography and to provide
      essential clinical tips for its use in the diagnosis and management of glaucoma.

PMID- 29055904
TI  - Prevalence of blindness and cataract surgical coverage in Narayani Zone, Nepal: a
      rapid assessment of avoidable blindness (RAAB) study.
AB  - BACKGROUND: The 1981 Nepal Blindness Survey first identified the Narayani Zone as
      one of the regions with the highest prevalence of blindness in the country.
      Subseuqently, a 2006 survey of the Rautahat District of the Narayani Zone found
      it to have the country's highest blindness prevalence. This study examines the
      impact on blind avoidable and treatable eye conditions in this region after
      significant increase in eye care services in the past decade. METHODS: The rapid
      assessment of avoidable blindness (RAAB) methodology was used with mobile data
      collection using the mRAAB smartphone app. Data analysis was done using the
      standard RAAB software. Based on the 2011 census, 100 clusters of 50 participants
      aged 50 years or older were randomly sampled proportional to population size.
      RESULTS: Of the 5000 participants surveyed, 4771 (95.4%) were examined. The age
      adjusted and sex-adjusted prevalence of bilateral blindness, severe visual
      impairment (SVI) and moderate visual impairment (MVI) were 1.2% (95% CI 0.9% to
      1.5%), 2.5% (95% CI 2.0% to -3.0%) and 13.2% (95% CI 11.8% to 14.5%),
      respectively. Cataract remains the primary cause of blindness and SVI despite
      cataract surgery coverage (CSC) of 91.5% for VA<3/60. Women still account for two
      thirds of blindness. CONCLUSION: The prevalence of blindness in people over the
      age of 50 years has decreased from 6.9% in 2006 to 1.2%, a level in keeping with
      the national average; however, significant gender inequity persists. CSC has
      improved but continues to favour men.

PMID- 29055906
TI  - Orbital trapdoor fractures: different clinical profiles between adult and
      paediatric patients.
AB  - BACKGROUND: To compare clinical findings of orbital trapdoor fractures between
      adult and paediatric patients. METHODS: Paediatric patients were categorised into
      two groups by age: children (0-9 years) and adolescents (10-19 years). Adult
      patients were categorised into two groups by age: early (20-44 years) and middle
      late adulthood (>=45 years). Demographic data, ocular and periocular
      complications, CT findings and binocular single vision field (BSVF) were compared
      among age groups. RESULTS: This study included 105 patients (105 sides, 22
      children, 59 adolescents, 14 patients in early adulthood and 10 patients in
      middle-late adulthood). In patients with fractures of the orbital floor and
      medial wall, both walls presented as trapdoor fractures in paediatric patients,
      while one wall presented as a non-trapdoor fracture in adult patients (p=0.061).
      None of the adult patients showed extraocular muscle incarceration, whereas this
      was present in 8 of 22 children (36.4%) and 7 of 59 adolescents (11.9%)
      (p=0.005). Hypoesthesia of the infraorbital nerve more frequently occurred in
      adults (p=0.004). As the preoperative BSVF was larger in adult than in paediatric
      patients (p=0.007), the percentage of adult patients who underwent surgical
      reduction of orbital fractures tended to be lower (p=0.058). Postoperative change
      in BSVF was smaller in adult patients (p=0.005). CONCLUSIONS: Fracture pattern,
      type of incarcerated tissue and incidence of hypoesthesia of the infraorbital
      nerve were different between adult and paediatric patients. Adult patients had a
      larger preoperative BSVF and less need for surgical reduction; however, there was
      less improvement in postoperative BSVF.

PMID- 29055907
TI  - Stage distribution of screen-detected colorectal cancers in the Netherlands.

PMID- 29055909
TI  - Serrated polyposis syndrome may go undiagnosed even in structured colorectal
      cancer screening programmes performed by endoscopists with otherwise good quality
      indices.

PMID- 29055908
TI  - High risk of hepatocellular carcinoma and death in patients with immune-tolerant
      phase chronic hepatitis B.
AB  - OBJECTIVE: High serum HBV DNA levels are associated with high risks of
      hepatocellular carcinoma (HCC) and cirrhosis in patients with chronic hepatitis B
      (CHB). Although the immune-tolerant (IT) phase is characterised by high
      circulating HBV DNA levels, it remains unknown whether antiviral treatment
      reduces risks of HCC and mortality. DESIGN: This historical cohort study included
      HBeAg-positive patients with CHB with high HBV DNA levels (>=20 000 IU/mL) and no
      evidence of cirrhosis at a tertiary referral hospital in Korea from 2000 to 2013.
      The clinical outcomes of 413 untreated IT-phase patients with normal alanine
      aminotransferase (ALT) levels (females, <19 IU/mL; males, <30 IU/mL) were
      compared with those of 1497 immune-active (IA)-phase patients (ALT >=80 IU/mL)
      treated with nucleos(t)ide analogues. RESULTS: The IT group was significantly
      younger than the IA group (mean age, 38 vs 40 years at baseline, p=0.04). The 10
      year estimated cumulative incidences of HCC (12.7% vs 6.1%; p=0.001) and
      death/transplantation (9.7% vs 3.4%; p<0.001) were significantly higher in the IT
      group than the IA group. In multivariable analyses, the IT group showed a
      significantly higher risk of HCC (HR 2.54; 95% CI 1.54 to 4.18) and
      death/transplantation (HR 3.38; 95% CI 1.85 to 6.16) than the IA group, which was
      consistently identified through inverse probability treatment weighting,
      propensity score-matched and competing risks analyses. CONCLUSIONS: Untreated IT
      phase patients with CHB had higher risks of HCC and death/transplantation than
      treated IA-phase patients. Unnecessary deaths could be prevented through earlier
      antiviral intervention in select IT-phase patients.

PMID- 29055910
TI  - ROC-king onwards: intraepithelial lymphocyte counts, distribution and role in
      coeliac disease mucosal interpretation.

PMID- 29055911
TI  - Guiding longitudinal sampling in IBD cohorts.

PMID- 29055912
TI  - Influence of Famine in Women with Non-Alcoholic Fatty Liver Disease.

PMID- 29055913
TI  - The Optimal Transfusion Strategy in Liver Transplantation: The Quest Continues.

PMID- 29055914
TI  - Evidence-Based Medicine and the Problem of Healthy Volunteers.
AB  - Healthy controls are subjects without the disease being studied but may have
      other conditions indirectly affecting outcome. In the present epidemics of
      obesity a few subjects with undiagnosed nonalcoholic fatty liver disease enter
      clinical studies as controls, producing biased results. Stricter selection
      criteria should be considered to prevent this risk.

PMID- 29055915
TI  - Search for Genetic Modifiers of PSC: Time to Increase the Number of Needles in
      the Haystack.
AB  - Primary sclerosing cholangitis (PSC) belongs to the most obscure liver diseases.
      Patients with progressive PSC require liver transplantation as only therapeutic
      option. Previously several HLA- and non-HLA-associated PSC risk variants have
      been discovered, however their involvement in the development of PSC seems to be
      minor in comparison to environmental determinants. Lately, variant rs853974 at
      the RSPO3 gene locus has been shown to modulate the course of PSC. Here we
      briefly discuss the phenotypes related to this polymorphism and propose
      alternative directions of research that might help to identify new genetic
      modifiers of PSC progression.

PMID- 29055916
TI  - The Great Chinese Famine Exposure in Early Life and the Risk of Nonalcoholic
      Fatty Liver Disease in Adult Women.
AB  - INTRODUCTION AND AIM: Previous studies found famine exposure was associated with
      a higher risk of metabolic syndrome (MetS). In the study, we investigated the
      relationship between Chinese famine exposure and the risk of nonalcoholic fatty
      liver disease (NAFLD) in adult women. MATERIALS AND METHODS: Data were obtained
      from subjects via routine physical examinations in the Public Health Center of
      our hospital between 2011 and 2014. Women were categorized into the following
      three groups: control, prenatally exposed, and postnatally exposed. Hepatic
      steatosis was diagnosed according to the guidelines established for the diagnosis
      and treatment of NAFLD. RESULTS: The prevalence rates of NAFLD among non-exposed,
      prenatally, and postnatally exposed women were 17.3, 23.0, and 22.9%,
      respectively. Pre-exposed and postnatally exposed women had higher risks of
      NAFLD, exhibiting ORs (95% CI) of 1.33 (1.04-1.70) and 1.26 (1.03-1.55),
      respectively. Prenatally, but not postnatally, exposed women had significantly
      higher risks of having abnormal alanine aminotransferase (ALT), with ORs of 1.30
      (1.05-1.61). CONCLUSIONS: The results indicate a significant association between
      famine exposure in early life and the risk of NAFLD in adult women. Prenatally
      exposed women displayed higher risks of NAFLD and mild, moderate and severe
      steatosis.

PMID- 29055917
TI  - Burden of Chronic Viral Hepatitis and Liver Cirrhosis in Brazil - the Brazilian
      Global Burden of Disease Study.
AB  - INTRODUCTION AND AIM: Data on epidemiology of liver diseases in Brazil is scarce.
      This study aimed to estimate the burden of chronic viral hepatitis and liver
      cirrhosis in the country. MATERIALS AND METHODS: The indicator used was
      disability-adjusted life year (DALY), a sum of years of life lost due to
      premature mortality (YLL) and years lived with disability (YLD). Liver cirrhosis
      was analyzed in etiologic categories and cirrhosis of viral origin was considered
      part of the burden of chronic hepatitis. RESULTS: There were 57,380 DALYs (30.3
      per 100,000 inhabitants) attributable to chronic hepatitis B and cirrhosis due to
      hepatitis B, with 41,262 DALYs in men. Most burden was caused by YLL (47,015 or
      24.8/100,000) rather than YLD (10,365 or 5.5/100,000). Chronic hepatitis C and
      cirrhosis due to hepatitis C were responsible for 207,747 DALYs (109.6/100,000),
      of which 137,922 were YLL (72.7/100,000) and 69,825 (36.8/100,000) were YLD, with
      a higher proportion of DALYs in men (73.9%). Cirrhosis due to alcohol or other
      causes had a total of 536,169 DALYs (1,4% of total DALYs in Brazil), with 418,272
      YLL (341,140 in men) and 117,897 YLD (97,965 in men). Highest DALYs' rates
      occurred at ages 60-69 in chronic hepatitis and at ages 45-59 in cirrhosis due to
      alcohol or other causes. CONCLUSION: Chronic viral hepatitis and liver cirrhosis
      are responsible for a significant burden in Brazil, affecting mainly men and
      individuals still in their productive years. Most burden is related to non-viral
      causes of cirrhosis, with a major contribution of alcohol.

PMID- 29055918
TI  - Rotational Thromboelastometry or Conventional Coagulation Tests in Liver
      Transplantation: Comparing Blood Loss, Transfusions, and Cost.
AB  - INTRODUCTION: Orthotopic liver transplantation (OLT) can be associated with
      significant bleeding requiring multiple blood product transfusions. Rotational
      thromboelastometry (ROTEM) is a point-of-care device that has been used to
      monitor coagulation during OLT. Whether it reduces blood loss/transfusions during
      OLT remains controversial. MATERIALS AND METHODS: We aim to compare ROTEM with
      conventional coagulation tests (aPTT, PT, INR, platelet count, fibrinogen) to
      guide transfusion of platelets, cryoprecipitate, and fresh frozen plasma (FFP)
      during OLT over 3 years. Thirty-four patients who had transfusions guided by
      ROTEM were compared to 34 controls who received transfusions guided by
      conventional coagulation tests (CCT). Intraoperative blood loss, type/ amount of
      blood products transfused, and direct costs were compared between the two groups.
      RESULTS: The ROTEM group had significantly less intra-operative blood loss (2.0
      vs. 3.0 L, p = 0.04) and fresh frozen plasma (FFP) transfusion (4 units vs. 6.5
      units, p = 0.015) compared to the CCT group (2.0L vs. 3.0L, p = 0.04). However,
      total number of patients transfused cryoprecipitate was increased in ROTEM (n =
      25;73%) as compared to CCT (n = 19; 56%), p = 0.033. The direct cost of blood
      products plus testing was reduced in the ROTEM group ($113,142.89 vs.
      $127,814.77). CONCLUSION: In conclusion implementation of a ROTEM-guided
      transfusion algorithm resulted in a reduction in intra-operative blood loss, FFP
      transfusion and a decrease in direct cost during OLT. ROTEM is a useful and safe
      point of care device in OLT setting.

PMID- 29055919
TI  - The Expression of PNPLA3 Polymorphism could be the Key for Severe Liver Disease
      in NAFLD in Hispanic Population.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) encompasses: fatty liver
      (SS), steatohepatitis (NASH) with or without fibrosis and cirrhosis. Patatine
      like phosphatas in domain 3 (PNPLA3; adiponutrin; SNP rs738409 C/G, M148I) shows
      anabolic and catabolic activities on lipid metabolism and significant association
      to fatty liver content; however, I148M demographics and ethnics, as its role with
      NAFLD have not been fully elucidated. MATERIAL AND METHODS: PNPLA3 genotyping
      from peripheral blood DNA by polymerase chain reaction (PCR) and direct
      sequencing, 211 patients diagnosed with NAFLD including SS, NASH and fibrosis
      spectrum. RESULTS: Eighty nine per cent showed the G risk allele [CC: 23 (10.5%),
      GC: 73 (34.7%), GG 115 (54.7%)], the allele frequency was 77%, NASH (71%), SS
      (80%) and fibrosis (73%). GG genotype carriers showed 3.8 times (CI 95%: 3.03 -
      4.79) of increased risk of steatohepatitis and 2.3 times more (CI 95%: 1.77 ~
      3.23) risk of having liver fibrosis (CC). PNPLA3 (GC, GG) conditioned higher
      probability of low levels of HDL cholesterol (p < 0.010), SS even in normal
      weight (p < 0.007), insulin resistance by HOMA (p < 0.029), NAFLD fibrosis score
      showed > 0.675 (p < 0.001) and altered serum alanine aminotransferase (p < 0.05).
      CONCLUSION: PNPLA3 expression in Hispanics could be decisive in NAFLD
      pathogenesis, it's highly prevalent and it's a key to condition and determine the
      spectrum associated, SS, NASH and fibrosis.

PMID- 29055920
TI  - Curcumin in Hepatobiliary Disease: Pharmacotherapeutic Properties and Emerging
      Potential Clinical Applications.
AB  - Curcumin, an aromatic phytoextract from the turmeric (Curcuma longa) rhizome, has
      been used for centuries for a variety of purposes, not the least of which is
      medicinal. A growing body of evidence suggests that curcumin has a broad range of
      potentially therapeutic pharmacological properties, including anti-inflammatory,
      anti-fibrotic, and anti-neoplastic effects, among others. Clinical applications
      of curcumin have been hampered by quality control concerns and limited oral
      bioavailability, although novel formulations appear to have largely overcome
      these issues. Recent in vitro and in vivo studies have found that curcumin's
      cytoprotective and other biological activities may play a role in an array of
      benign and malignant hepatobiliary conditions, including but not limited to non
      alcoholic fatty liver disease, cholestatic liver disease (e.g. primary sclerosing
      cholangitis), and cholangiocarcinoma. Here we provide an overview of fundamental
      principles, recent discoveries, and potential clinical hepatobiliary applications
      of this pleiotropic phytocompound.

PMID- 29055921
TI  - Hepatitis C and Its Metabolic Complications in Kidney Disease.
AB  - INTRODUCTION: Evidence has been accumulated during the last decade showing that
      HCV infection plays an important activity at hepatic and extra-hepatic level.
      Chronic HCV is associated with a large spectrum of extra-hepatic manifestations
      including lympho-proliferative diseases and metabolic abnormalities (such as
      insulin resistance and fatty liver disease). MATERIAL AND METHODS: We have
      performed an extensive review of the medical literature regarding the increased
      risk of cardiovascular and kidney disease that has been observed in various
      groups of HCV-infected patients. The potential link between such increased risk
      and the metabolic consequences of chronic HCV infection has been explored.
      RESULTS: According to a systematic review with a meta-analysis of longitudinal
      studies (n = 9 clinical observational studies; n = 1,947,034 unique patients), we
      found a strong relationship between positive anti-HCV serologic status and
      increased incidence of chronic kidney disease in the adult general population,
      the summary estimate for adjusted hazard ratio was 1.43 (95% confidence
      intervals, 1.23; 1.63, P = 0.0001) (random-effects model) in anti-HCV positive
      patients. In another meta-analysis of clinical observational studies (n = 145,608
      unique patients on long term dialysis; n = 14 observational studies), anti-HCV
      sero-positive status was an independent and significant risk factor for death in
      patients on maintenance dialysis. The summary estimate for adjusted relative risk
      (all-cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25; 1.47
      (P < 0.01) in anti-HCV positive patients on maintenance dialysis. An updated and
      stratified analysis (n = 4 studies, n = 91,916 patients on maintenance dialysis)
      resulted in an adjusted HR for cardiovascular mortality among anti-HCV positive
      patients of 1.21 (95% CI, 1.06; 1.39) (P < 0.01); the homogeneity assumption was
      not rejected. The mechanisms underlying such relationships remain unclear; it has
      been suggested that HCV promotes atherogenesis through direct and indirect
      mechanisms. CONCLUSIONS: Clinical trials are under way to assess whether the
      clearance of HCV RNA from serum by direct-acting antiviral drugs reduces all
      cause or disease-specific (cardiovascular) mortality among patients on
      maintenance dialysis.

PMID- 29055922
TI  - Endoscopic Management of Primary Sclerosing Cholangitis.
AB  - Primary sclerosing cholangitis (PSC) remains a rare but potentially devastating
      chronic, cholestatic liver disease. PSC causes obstruction of intra- and/or extra
      hepatic bile ducts by inflammation and fibrosis, leading to biliary obstruction,
      cirrhosis and portal hypertension with all associated sequelae. The most dreaded
      consequence of PSC is cholangiocarcinoma, occurring in 10-20% of patients with
      PSC, and with population-based estimates of a 398-fold increased risk of
      cholangiocarcinoma in patients with PSC compared to the general population. We
      use the 4-D approach to endoscopic evaluation and management of PSC based on
      currently available evidence. After laboratory testing with liver chemistries and
      high-quality cross-sectional imaging with MRCP, the first D is Dominant stricture
      diagnosis and evaluation. Second, Dilation of strictures found during ERCP is
      performed using balloon dilation to as many segments as possible. Third,
      Dysplasia and cholangiocarcinoma diagnosis is performed by separated brushings
      for conventional cytology and fluorescence in situ hybridization (FISH), and
      consideration for direct cholangioscopy with SpyGlassTM. Fourt and finally,
      Dosing of antibiotics is critical to prevent peri-procedural cholangitis. The aim
      of this review article is to explore endoscopic tools and techniques for the
      diagnosis and management of PSC and provide a practical approach for clinicians.

PMID- 29055923
TI  - Direct-Acting Antiviral Therapy Outcomes in Canadian Chronic Hepatitis C
      Telemedicine Patients.
AB  - INTRODUCTION: Many of the 300,000 HCV-infected Canadians live in under-served and
      remote areas without access to HCV healthcare specialists. Telemedicine (TM) and
      advances in HCV management can facilitate linkage of these marginalized patients
      to healthcare. MATERIALS AND METHODS: A cohort database analysis was performed on
      patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program
      between January 2012 and August 2016. We compared patient characteristics,
      fibrosis work-up and antiviral treatment outcomes in TM (n = 157) and non-TM (n =
      1,130) patients (The Ottawa Hospital Viral Hepatitis Outpatient Clinic) residing
      in Eastern Ontario. RESULTS: TM patients were more often infected with genotype 3
      (25.9% vs. 16.4%), were more commonly Indigenous (7.0% vs. 2.2%) had a history of
      injection drug use (70.1% vs. 54.9%) and incarceration (46.5% vs 35.5%). Groups
      were comparable in age (48.9 years), gender (63.7% male) and cirrhotic stage
      (24.0%). 59.2% of TM patients underwent transient elastography during regional
      outreach blitzes compared to 61.8% of non-TM patients (p = 0.54). Overall, half
      as many TM patients initiated antiviral therapy as non-TM patients (27.4% vs.
      53.8%, p < 0.001). The introduction of DAA regimens is bridging this gap (22.2%
      of TM patients vs. 34.3% of non-TM patients). SVR rates with interferon-free, DAA
      regimens were 94.7% and 94.8% in TM and non-TM groups (p = 0.99). CONCLUSION: Our
      TM program engages and retains a population that faces many barriers to effective
      HCV treatment. TM patients initiated HCV therapy and achieved High SVR rates
      comparable to those obtained using traditional models of care.

PMID- 29055924
TI  - Fibrogenic/Angiogenic Linker for Non-Invasive Assessment of Hepatic Fibrosis
      Staging in Chronic Hepatitis C Among Egyptian Patients.
AB  - : Background and rationale for the study. Liver biopsy is the golden standard for
      staging liver fibrosis, but it may be accompanied by complications. Because of
      this complication, the aim of this study is to evaluate a simple noninvasive
      score to assess hepatic fibrosis in chronic hepatitis C genotype 4 patients which
      is very may have an important in diagnosis and therapeutic decision. This score
      [HA vascular (HAV) score] is a combination of direct markers [hyaluronic acid
      (HA) and vascular endothelial growth factor (VEGF)] and indirect markers
      [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)].
      RESULTS: Samples were collected from 220 patients (F0-F4): an estimated group (n
      = 120) and a validated group (n = 100). HA and VEGF levels, HCV RNA, liver
      function tests, platelet counts were assayed, Fibroscan was done and liver biopsy
      was taken and the stage of liver fibrosis and the grade of inflammatory activity
      was calculated according to Metavir score system. HA vascular (HAV) score = -35.1
      + 0.14 (HA) (ng/L) + 0.03 (VEGF) (pg/mL) + (-6.7) [AAR (AST/ALT ratio)]. The HAV
      score produced areas under curve of 0.979 and 0.994 for significant (F2-F4) and
      advanced fibrosis (F3-F4) (cut off = 0.583 and 6.3, respectively). Surprisingly,
      the validation study of this score gave very good values of AUCs i.e. 0.990,
      0.996 and 0.995 for significant, advanced and liver cirrhosis. CONCLUSIONS: Our
      developed score can not only help to assess liver fibrosis staging effectively
      but also avoid the invasiveness and the limitations of liver biopsy in Egyptian
      hepatitis C virus patients.

PMID- 29055925
TI  - Clinical Analysis of Polyethylene Glycol Interferon-alpha Treatment in 155
      Hepatitis B e Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) Patients.
AB  - PURPOSE: This study aims to investigate the antiviral effect of polyethylene
      glycol (PEG)-interferon alpha-2a and PEG-interferon alpha-2b treatment on
      hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) at the 48th week
      of treatment and the 24th and 48th week after withdrawal, in order to provide
      guidance on the antiviral treatment of HBeAg-positive CHB patients. MATERIAL AND
      METHODS: Antiviral treatment was performed on 155 HBeAg-positive CHB patients.
      Among these patients, 66 patients received PEG-interferon alpha-2a treatment and
      89 patients received PEG-interferon alpha-2b treatment; and these treatments were
      administered by subcutaneous injection, once per week, which lasted for 48 weeks.
      Other antiviral and hepatoprotective drugs were not used during the treatment.
      RESULTS: At the 48th week of treatment, ALT recovery rate, HBsAg seroconversion
      rate, HBeAg seroconversion rate and HBV DNA titers dropped below 200 IU/mL rate
      were 69.7%, 6.1%, 27.3% and 50.0%, respectively, in the PEG-interferon alpha-2a
      group; and were 70.8%, 6.7%, 33.7% and 62.9%, respectively, in the PEG-interferon
      alpha-2b group. At the 24th and 48th week of follow-up after withdrawal, HBsAg
      seroconversion rate in these two groups did not change; and HBeAg seroconversion
      rate further increased. Furthermore, HBV DNA revealed a low recurrence rate. The
      difference between these two groups was not significantly significant.
      CONCLUSIONS: PEG-interferon alpha-2a and PEG-interferon alpha-2b are effective
      antiviral drugs for the treatment of HbeAgpositive CHB, which has a HBsAg
      seroconversion rate of more than 5%. Furthermore, this sustained response effect
      was maintained at the 24th and 48th week of follow-up after withdrawal.

PMID- 29055926
TI  - An Inexpensive Digital Image Analysis Technique for Liver Fibrosis Quantification
      in Chronic Hepatitis B Patients.
AB  - BACKGROUND AND AIM: Quantitative digital imaging analysis to evaluate liver
      fibrosis is accurate, but its clinical use is limited by its high cost and lack
      of standardization. We aimed to validate an inexpensive digital imaging analysis
      technique for fibrosis quantification in chronic hepatitis B patients. MATERIAL
      AND METHODS: In total, 142 chronic hepatitis B patients who underwent liver
      biopsy and analysis of serum fibrosis markers were included. Images of Sirius red
      stain sections were captured and processed using Adobe Photoshop CS3 software.
      The percentage of fibrosis (fibrosis index) was determined by the ratio of the
      fibrosis area to the total sample area, expressed in pixels, and calculated
      automatically. RESULTS: A strong correlation between the fibrosis index and the
      Ishak, Metavir, and Laennec histological staging systems were observed (r = 0.83,
      0.86, and 0.84, respectively; < 0.001). The cutoff value associated with
      cirrhosis was 7.7% with an area under the receiver operating characteristic curve
      (AUROC) of 0.95 (95% confidence interval [CI], 0.92-0.99, p < 0.001).
      Furthermore, the fibrosis index yielded a cutoff value of 8.9% (AUROC, 0.74; 95%
      CI, 0.66-0.86), 12% (AUROC, 0.84; 95% CI, 0.75-0.93), and 14% (AUROC, 0.97; 95%
      CI, 0.92-1.0) for the diagnosis of cirrhosis 4a, 4b, and 4c, respectively. No
      serum markers or fibrosis models were correlated with the fibrosis index in
      Metavir F2-F4. CONCLUSIONS: The present digital imaging analysis technique is
      reproducible and available worldwide, allowing its use in clinical practice, and
      can be considered as a complementary tool to traditional histological methods.

PMID- 29055927
TI  - Could TIPS be Applied in All Kinds of Portal Vein Thrombosis: We are not Sure!

PMID- 29055928
TI  - New Onset Diabetes and Non-Alcoholic Fatty Liver Disease after Liver
      Transplantation.
AB  - BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging cause
      of graft dysfunction after liver transplantation (LT) frequently related to the
      development of new onset diabetes after LT (NODAT). This study was undertaken to
      evaluate the frequencies of NODAT and NAFLD after LT, to investigate their major
      risk factors and the impact of de novo or recurrent NAFLD in graft function.
      MATERIAL AND METHODS: 119 patients submitted to LT were prospectively evaluated.
      RESULTS: After 4 +/- 1 years, NODAT, recurrent and de novo NAFLD were observed in
      31%, 56% and 43% of the subjects, respectively. Only 3 patients had non-alcoholic
      steatohepatitis (NASH) without fibrosis. Other risk factors for NAFLD such as
      arterial hypertension (AHT), metabolic syndrome (MS), hypertriglyceridemia and
      obesity were seen in 51%, 50%, 35% and 24% of the subjects, respectively. In
      addition, insulin resistance (IR), assessed by HOMA-IR and beta-cell dysfunction,
      determined by HOMA-beta, were observed in 16% and 94% of the patients,
      respectively. Occurrence of NODAT was associated with male gender, higher waist
      circumference, higher HOMA-IR and lower HOMA-beta values. No correlation was
      found between NAFLD and NODAT, MS, hypertriglyceridemia, obesity and HOMAIR and
      HOMA-beta levels. CONCLUSIONS: NODAT, recurrent and de novo NAFLD are common
      after LT but are not associated with signs of graft dysfunction, possibly due to
      the low frequency of IR and NASH. No correlation is observed between NAFLD and
      NODAT, MS, hypertriglyceridemia, obesity and IR. beta-cell dysfunction and
      diabetes, however, are seen in most of the patients, possibly due to calcineurin
      inhibitor toxicity.

PMID- 29055929
TI  - Endoscopic Therapy is Effective for Recurrent Anastomotic Biliary Strictures
      after Orthotopic Liver Transplantation.
AB  - INTRODUCTION: Orthotopic liver transplantation anastomotic biliary strictures
      (OLT ABS) are managed with endoscopic biliary stent therapy but the recurrence
      rate is substantial. Our aims were to retrospectively determine the recurrence
      rates of OLT ABS after initial successful stent therapy, characterize the
      management of recurrences and identify associated variables. MATERIALS AND
      METHODS: Clinical data from 943 patients receiving non-living donor OLT at our
      institution from 2005-2012 were reviewed, and 123 OLT ABS patients receiving
      stent therapy were identified. Features of their endoscopic stent therapy and
      other pertinent clinical information were evaluated. RESULTS: ABS recurred in
      25.5% of patients (24/94) after an initial successful course of stent therapy.
      Recurrences were received a second course of endoscopic stent therapy and 67% of
      patients (16/24) achieved long-term remediation of ABS. Six patients underwent a
      third course of endoscopic stent therapy with 4 patients achieving remediation.
      Overall remediation rate among ABS recurrences was 83.3% (20/24). A bivariate
      comparison demonstrated HCV infection, age, median months of maximal stenting and
      a lower maximum cumulative stent diameter were risk factors for ABS recurrence.
      Using a Cox regression model, only HCV status proved to be a risk factor for
      recurrence. DISCUSSION: In conclusion repeat stent therapy achieved high
      stricture remediation rates. Recurrence after the first or even second course of
      stenting should not imply failure of endoscopic therapy. A positive HCV status
      may be associated with higher stricture recurrence rates and this association
      should be further investigated.

PMID- 29055930
TI  - Analysis of the MELD Score Impact in the Outcome of Endovascular Portal Vein
      Reconstruction.
AB  - INTRODUCTION: Endovascular therapy represents a less invasive alternative to open
      surgery for reconstruction of the portal vein (PV) and the spleno-mesenteric
      venous confluence to treat Portal hypertension. The objective of this study is to
      determine if the Model for End-Stage Liver Disease (MELD) score is a useful
      method to evaluate the risk of morbidity and mortality during endovascular
      approaches. MATERIAL AND METHODS: Patients that underwent endovascular
      reconstruction of the PV or spleno-mesenteric confluence were identified
      retrospectively. Data were collected from November 2011 to August 2016. The MELD
      score was calculated using international normalized ratio, serum billirubin and
      creatinine. Patients were grouped into moderate (<= 15) and high (> 15) MELD.
      Associations of the MELD score on the postprocedural morbidity, mortality and
      vessels patency were assessed by two-sided Fisher's exact test. RESULTS:
      Seventeen patients were identified; MELD score distribution was: <= 15 in 10
      patients (59%) and > 15 in 7 (41%). Even distribution of severe PV thrombosis was
      treated in both groups, performing predominately jugular access in the high MELD
      score group (OR 0.10; 95%; CI 0.014-0.89; p = 0.052) in contrast to a
      percutaneous transhepatic access in the moderate MELD score group. Analysis
      comparing moderate and high MELD scores was not able to demonstrate differences
      in mortality, morbidity or patency rates. CONCLUSION: MELD score did not prove to
      be a useful method to evaluate risk of morbidity and mortality; however a high
      score should not contraindicate endovascular approaches. In our experience a high
      technical success, good patency rates and low complication rates were observed.

PMID- 29055931
TI  - Congenital Shunts of the Portal Venous System: Case-series of Uncommon Shunts.
AB  - BACKGROUND AND AIMS: Congenital shunts of the portal venous system are rare
      entities that can present in children with clinical heterogeneity. To evaluate
      the clinical course of children with uncommon shunts presenting to our
      institution and examine the available literature on this topic. Medical records
      of children with rare forms of congenital shunts were retrospectively reviewed
      for demographics, symptoms, management, and outcome between 2003 and 2016.
      RESULTS: Three female patients with congenital shunts, including a congenital
      mesenterico-portal Rex shunt (n = 1) and congenital portosystemic shunts (CPSS)
      (n = 2), were referred for surgical evaluation between ages 4 and 9. Median
      follow-up was 8 years (range, 6-13 years). One asymptomatic patient did not
      require treatment and remained disease-free during long-term follow-up. The other
      2 patients with CPSS and unusual symptoms, including liver focal nodular
      hyperplasia (FNH) in infancy (n = 1) and bleeding from esophageal varices (n =
      1), showed subsequent progression to liver nodules that were managed by
      endovascular shunt occlusion. One patient showed symptom resolution and the other
      showed stable lesions at last follow-up. Literature yielded descriptions of two
      cases of congenital mesenterico-portal Rex shunt, one case of coincident CPSS and
      FNH in infancy, but zero reports of bleeding from esophageal varices.
      CONCLUSIONS: This case series examines each distinct patient's presentation,
      discusses the diagnosis, management and outcome and compares findings while
      discussing literature on this topic. A high index of suspicion and familiarity
      with unusual forms and treatment options is required to allow timely diagnosis
      and appropriate treatment.

PMID- 29055932
TI  - Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic
      Cardiomyopathy.
AB  - At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in
      the literature. We report a hepatocellular carcinoma patient with cardiac
      metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later,
      on presentation of syncope, an abnormal ventricular septal size was recorded by
      ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a
      tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular
      carcinoma. This observation underlines the risk of hepatocellular carcinoma
      cardiac metastasis, manifested in its infiltrative form as hypertrophic
      cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of
      hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen
      as a "red flag" and recommend the introduction of magnetic resonance imaging
      assessment of transplant candidates.

PMID- 29055933
TI  - Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the
      Severity of Liver Disease in Rodents.
AB  - BACKGROUND: Acute exposure to high concentrations of microcystin-LR (MC-LR) can
      cause significant hepatocyte injury. AIM: To document the effects of long-term,
      low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy
      and diseased livers. MATERIAL AND METHODS: Male CD1 mice (N = 20/group) were
      exposed to 1.0 MUg/L of MC-LR in drinking water; 1.0 MUg/L MC-LR plus 300 mg/L of
      the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks.
      Liver biochemistry and histology were documented at the end of the study period.
      In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1
      10,000 MUg/L) and monitored for changes in cell metabolism, proliferation and
      activation. RESULTS: Liver biochemistry and histology were essentially normal in
      MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant
      hepatic inflammation and fibrosis but the extent of the changes were similar in
      the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or
      activation. CONCLUSION: Long-term, low-dose exposure to MC-LR is unlikely to lead
      to chronic liver disease in the setting of a normal liver or exacerbate existing
      liver disease in the setting of ongoing hepatitis.

PMID- 29055935
TI  - A cost-sensitive Bayesian combiner for reducing false positives in mammographic
      mass detection.
AB  - Mammography is the most widely used modality for early breast cancer detection.
      This work proposes a new computer-aided mass detection approach, in which a
      denoising method called BM3D is first applied to mammograms. Afterwards, using an
      adaptive segmentation algorithm, images are segmented to suspicious regions of
      interest (ROIs) and then a classifier is used to understand the features of true
      positive (TP) and false positive (FP) patterns. In this way, from selected
      suspicious ROIs, fractal dimension, texture and intensity features are extracted.
      Subsequently, a discretization approach followed by correlation-based feature
      selection (CFS) is combined with a genetic algorithm to obtain the most
      representative features. To neutralize the classifier's bias in favor of the
      major class in imbalanced datasets, an oversampling algorithm is used. In the
      next step, a cost-sensitive ensemble classifier based on a trainable combiner is
      proposed in order to reduce the number of FP samples. Finally, the presented
      method is validated on miniMIAS and INBreast datasets. The free-response receiver
      operating characteristic (FROC) analysis results prove the efficiency of the
      proposed approach. A sensitivity of 88% and false positive per image (FPpI) of
      0.78 for miniMIAS and also a sensitivity of 86% and FPpI of 0.75 for INBreast
      dataset were obtained.

PMID- 29055934
TI  - Cryptogenic Cirrhosis and Sitosterolemia: A Treatable Disease If Identified but
      Fatal If Missed.
AB  - Sitosterolemia is an autosomal recessive metabolic disease caused by mutations in
      ABCG5 or ABCG8 genes which encode for the (ATP)-binding cassette (ABC)
      transporters that are responsible for the trafficking of xenosterols. Liver
      involvement is not a recognized manifestation of this disease, and cirrhosis has
      been reported only once in the medical literature. We describe a fatal case of a
      21-year old South Asian male who presented with decompensated cirrhosis, and
      biochemical abnormalities consistent with sitosterolemia. Genetic testing showed
      a homozygous pathogenic mutation in ABCG5, confirming the diagnosis.
      Sitosterolemia is a rare, but likely under-recognized condition, and a high
      degree of suspicion is imperative to make the diagnosis. We propose that
      sitosterolemia should be included in the differential diagnosis for patients with
      cryptogenic cirrhosis, especially as there are effective oral therapies to treat
      this condition. Newly diagnosed sitosterolemia patients should undergo a thorough
      hepatology evaluation and follow-up to evaluate for the presence, development,
      and progression of any hepatic involvement.

PMID- 29055936
TI  - Machine learning in laboratory medicine: waiting for the flood?
AB  - This review focuses on machine learning and on how methods and models combining
      data analytics and artificial intelligence have been applied to laboratory
      medicine so far. Although still in its infancy, the potential for applying
      machine learning to laboratory data for both diagnostic and prognostic purposes
      deserves more attention by the readership of this journal, as well as by
      physician-scientists who will want to take advantage of this new computer-based
      support in pathology and laboratory medicine.

PMID- 29055937
TI  - Reaching consensus on communication of critical laboratory results using a
      collective intelligence method.
AB  - BACKGROUND: There is no consensus in the literature about what analytes or values
      should be informed as critical results and how they should be communicated. The
      main aim of this project is to establish consensual standards of critical results
      for the laboratories participating in the study. Among the project's secondary
      objectives, establishing consensual procedures for communication can be
      highlighted. METHODS: Consensus was reached among all participating laboratories
      establishing the basis for the construction of the initial model put forward for
      consensus in conjunction with the clinicians. A real-time Delphi, methodology
      "health consensus" (HC), with motivating and participative questions was applied.
      The physician was expected to choose a numeric value within a scale designed for
      each analyte. RESULTS: The medians of critical results obtained represent the
      consensus on critical results for outpatient and inpatient care. Both in primary
      care and in hospital care a high degree of consensus was observed for critical
      values proposed in the analysis of creatinine, digoxin, phosphorus, glucose,
      international normalized ratio (INR), leukocytes, magnesium, neutrophils,
      chloride, sodium, calcium and lithium. For the rest of critical results the
      degree of consensus obtained was "medium high". The results obtained showed that
      in 72% of cases the consensual critical value coincided with the medians
      initially proposed by the laboratories. CONCLUSIONS: The real-time Delphi has
      allowed obtaining consensual standards for communication of critical results
      among the laboratories participating in the study, which can serve as a basis for
      other organizations.

PMID- 29055938
TI  - Visual assessment of sample quality: quo usque tandem?

PMID- 29055939
TI  - The National Institute of Environmental Health Sciences Superfund Research
      Program: a model for multidisciplinary training of the next generation of
      environmental health scientists.
AB  - The National Institute of Environmental Health Sciences (NIEHS) Superfund
      Research Program (SRP) funds university-based, multidisciplinary research on
      human health and environmental science and engineering with the central goals to
      understand how hazardous substances contribute to disease and how to prevent
      exposures to these environmental chemicals. This multi-disciplinary approach
      allows early career scientists (e.g. graduate students and postdoctoral
      researchers) to gain experience in problem-based, solution-oriented research and
      to conduct research in a highly collaborative environment. Training the next
      generation of environmental health scientists has been an important part of the
      SRP since its inception. In addition to basic research, the SRP has grown to
      include support of broader training experiences such as those in research
      translation and community engagement activities that provide opportunities to
      give new scientists many of the skills they will need to be successful in their
      field of research. Looking to the future, the SRP will continue to evolve its
      training component by tracking and analyzing outcomes from its trainees by using
      tools such as the NIEHS CareerTrac database system, by increasing opportunities
      for trainees interested in research that goes beyond US boundaries, and in the
      areas of bioinformatics and data integration. These opportunities will give them
      the skills needed to be competitive and successful no matter which employment
      sector they choose to enter after they have completed their training experience.

PMID- 29055940
TI  - Biological and anatomical factors influencing interindividual variability to
      noninvasive brain stimulation of the primary motor cortex: a systematic review
      and meta-analysis.
AB  - Noninvasive brain stimulation (NIBS) modifies corticospinal excitability (CSE)
      historically in a predictable manner dependent on stimulation parameters.
      Researchers, however, discuss high degrees of variability between individuals,
      either responding as expected or not responding as expected. The explanation for
      this interindividual variability remains unknown with suggested interplay between
      stimulation parameters and variations in biological, anatomical, and
      physiological factors. This systematic review and meta-analysis aimed to
      investigate the effect of variation in inherent factors within an individual
      (biological and anatomical factors) on CSE in response to NIBS of the primary
      motor cortex. Twenty-two studies were included investigating genetic variation
      (n=7), age variation (n=4), gender variation (n=7), and anatomical variation
      (n=5). The results indicate that variation in brain-derived neurotrophic factor
      genotypes may have an effect on CSE after NIBS. Variation between younger and
      older adults also affects CSE after NIBS. Variation between age-matched males and
      females does not affect CSE after NIBS, but variation across the menstrual cycle
      does. Variation between skull thickness and brain tissue morphology influences
      the electric field magnitude that ultimately reaches the primary motor cortex.
      These findings indicate that biological and anatomical variations may in part
      account for interindividual variability in CSE in response to NIBS of the primary
      motor cortex, categorizing individuals as responding as expected (responders) or
      not responding as expected (nonresponders).

PMID- 29055941
TI  - A smoothed EM-algorithm for DNA methylation profiles from sequencing-based
      methods in cell lines or for a single cell type.
AB  - We consider the assessment of DNA methylation profiles for sequencing-derived
      data from a single cell type or from cell lines. We derive a kernel smoothed EM
      algorithm, capable of analyzing an entire chromosome at once, and to
      simultaneously correct for experimental errors arising from either the pre
      treatment steps or from the sequencing stage and to take into account spatial
      correlations between DNA methylation profiles at neighbouring CpG sites. The
      outcomes of our algorithm are then used to (i) call the true methylation status
      at each CpG site, (ii) provide accurate smoothed estimates of DNA methylation
      levels, and (iii) detect differentially methylated regions. Simulations show that
      the proposed methodology outperforms existing analysis methods that either ignore
      the correlation between DNA methylation profiles at neighbouring CpG sites or do
      not correct for errors. The use of the proposed inference procedure is
      illustrated through the analysis of a publicly available data set from a cell
      line of induced pluripotent H9 human embryonic stem cells and also a data set
      where methylation measures were obtained for a small genomic region in three
      different immune cell types separated from whole blood.

PMID- 29055942
TI  - Interaction of Excitatory Amino Acid Transporters 1 - 3 (EAAT1, EAAT2, EAAT3)
      with N-Carbamoylglutamate and N-Acetylglutamate.
AB  - BACKGROUND/AIMS: Inborn deficiency of the N-acetylglutamate synthase (NAGS)
      impairs the urea cycle and causes neurotoxic hyperammonemia. Oral administration
      of N-carbamoylglutamate (NCG), a synthetic analog of N-acetylglutamate (NAG),
      successfully decreases plasma ammonia levels in the affected children. Due to
      structural similarities to glutamate, NCG may be absorbed in the intestine and
      taken up into the liver by excitatory amino acid transporters (EAATs). METHODS:
      Using Xenopus laevis oocytes expressing either human EAAT1, 2, or 3, or human
      sodium-dependent dicarboxylate transporter 3 (NaDC3), transport-associated
      currents of NAG, NCG, and related dicarboxylates were assayed. RESULTS: L
      aspartate and L-glutamate produced saturable inward currents with Km values below
      30 uM. Whereas NCG induced a small inward current only in EAAT3 expressing
      oocytes, NAG was accepted by all EAATs. With EAAT3, the NAG-induced current was
      sodium-dependent and saturable (Km 409 uM). Oxaloacetate was found as an
      additional substrate of EAAT3. In NaDC3-expressing oocytes, all dicarboxylates
      induced much larger inward currents than did L-aspartate and L-glutamate.
      CONCLUSION: EAAT3 may contribute to intestinal absorption and hepatic uptake of
      NCG. With respect to transport of amino acids and dicarboxylates, EAAT3 and NaDC3
      can complement each other.

PMID- 29055944
TI  - Automatic Dialysis and Continuous Renal Replacement Therapy: Keeping the Primacy
      of Human Consciousness and Fighting the Dark Side of Technology.

PMID- 29055943
TI  - Suppression of Sirtuin-1 Increases IL-6 Expression by Activation of the Akt
      Pathway During Allergic Asthma.
AB  - BACKGROUND/AIMS: A growing number of studies have demonstrated that the activity
      and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients;
      however, the mechanisms underlying decreased SIRT1 expression and function are
      still not completely understood. Interleukin (IL)-6 plays important roles in
      inflammation during allergic asthma. In this study, we examined whether loss of
      SIRT1 activity regulated the expression of IL-6 and further verified the
      underlying mechanisms. METHODS: The human airway epithelial cell line 16HBE was
      used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL
      6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain
      reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an
      asthma model to investigate the effect of SIRT1 activation on IL-6 and relative
      Akt phosphorylation level. RESULTS: We found that inhibition of SIRT1 increased
      IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by
      increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt
      showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002
      or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely,
      activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic
      mice model and 16HBE cells. CONCLUSION: Our results indicate the potential role
      of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt
      dependent manner during allergic asthma.

PMID- 29055945
TI  - Bladder Metastases from Breast Cancer: Managing the Unexpected. A Systematic
      Review.
AB  - Breast cancer (BrC) has the highest incidence among females world over and it is
      one of the most common causes of death from cancer overall. Its high mortality is
      mostly due to its propensity to rapidly spread to other organs through lymphatic
      and blood vessels in spite of proper treatment. Bladder metastases from BrC are
      rare, with 50 cases having been reported in the last 60 years. This review aims
      to discuss some critical points regarding this uncommon condition. First, we
      performed a systematic review of the literature in order to draw a clinical and
      pathological profile of this entity. On this basis, its features in terms of
      diagnostic issues, imaging techniques, and survival are critically examined. Most
      bladder metastases from BrC are secondary lobular carcinoma, which mimic very
      closely the rare variant of urothelial cancer with lobular carcinoma-like
      features (uniform cells with an uncohesive single-cell, diffusely invasive growth
      pattern); thus, immunohistochemistry is mandatory to arrive at a correct
      diagnosis. This article summarizes the current knowledge regarding the incidence,
      clinical presentation, diagnosis, prognosis, and treatment of bladder metastases
      in patients with BrC.

PMID- 29055947
TI  - Preface.

PMID- 29055946
TI  - Socioeconomic Inequalities in Frailty among Older Adults: Results from a 10-Year
      Longitudinal Study in the Netherlands.
AB  - BACKGROUND: Frailty is an important risk factor for adverse outcomes in older
      people. Substantial variation in frailty prevalence between socioeconomic groups
      exists, but longitudinal evidence for the association between socioeconomic
      position (SEP) and frailty is scarce. OBJECTIVE: To investigate the course of
      socioeconomic inequalities in frailty among older adults during 10 years of
      follow-up. METHODS: Data were used from the Longitudinal Aging Study Amsterdam (n
      = 1,509). Frailty was measured with the functional domains approach, based on
      deficiencies in four domains: physical, nutritive, cognitive, and sensory. Mixed
      model analyses were performed to estimate the course of frailty and its
      association with SEP during a 10-year follow-up. We investigated whether similar
      patterns of associations held in different scenarios, comparing results of
      survivor analyses with those based on two imputation methods accounting for
      dropout due to death (substitution of first missing value and missing values
      imputed with a prediction model). RESULTS: All scenarios showed a linear increase
      in frailty with aging (survivor analyses OR = 1.87, 95% CI = 1.66-2.11) and
      associations of low education and low income with frailty (adjusted OR for low
      education = 1.76, 95% CI = 1.05-2.97; adjusted OR for low income = 1.90, 95% CI =
      1.20-3.01; both for survivor analyses). Sex-stratified analyses indicated that
      socioeconomic inequalities were mainly present in men, not in women. Similar
      patterns of associations of SEP with frailty were observed in all scenarios, but
      the increase in frailty prevalence over time differed substantially between the
      scenarios. There were no statistically significant interactions between time and
      SEP on frailty (all scenarios), suggesting that inequalities in frailty did not
      increase or decrease during follow-up. CONCLUSION: SEP inequalities in frailty
      among older adults were observed, mainly among men, and persisted during 10 years
      of follow-up.

PMID- 29055948
TI  - Avian Collagen Is Useful for the Construction of Skin Equivalents.
AB  - As a result of restrictions on animal experimentation, improved skin equivalents
      (SEs) are needed as alternative test models. This work investigated the effects
      of avian collagen on the construction of SEs, and to the best of our knowledge is
      the first study to do so. Hematoxylin and eosin and immunohistochemical staining
      were used to analyze the SEs. In models containing avian collagen as a dermal
      equivalent (DE) ingredient, fibroblast proliferation increased by about 60%
      relative to the control model. Immunohistochemical staining showed that the
      expression of proliferating cell nuclear antigen (PCNA) and p63 increased in the
      avian collagen models, while the expression of involucrin, integrin alpha6, and
      integrin beta1 remained unchanged. Next, DEs were cryopreserved to allow the
      easier creation of SEs. Keratinocytes were seeded on thawed DEs, and SEs were
      constructed. Avian collagen increased the viability of DEs relative to the
      control. Furthermore, avian collagen increased the expression of PCNA and p63 in
      keratinocytes on thawed DEs. The results indicate that DEs containing avian
      collagen can be thawed as needed after cryopreservation. Avian collagen can
      improve the construction of SEs and be used as part of a dermal kit for SE
      construction.

PMID- 29055949
TI  - Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells.
AB  - BACKGROUND: Expression of programmed death-ligand 1 (PD-L1) on tumor cells
      represents a powerful immune evasion pathway, but the role of intracellular or
      cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. METHODS:
      Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and
      western blot were used to determine the expression of PD-L1 in ovarian cancer
      cells. The cytokines detected in the tumor or tumor associated macrophage (TAM)
      were used to treat cancer cells. PD-L1 blockade and silencing were used to
      elucidate the functional significance of cancer-related PD-L1 expression.
      RESULTS: Based on the results presented, PD-L1 was found variably expressed in
      the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN
      gamma, TNF-alpha, IL-10 and IL-6 released from TAM stimulated the expression of
      PD-L1 at the surface of the cancer cells. The IHC results were consistent with
      the data in vitro showing infiltration of TAM correlated with membranous PD-L1.
      The increases of PD-L1 at the surface were not due to a shift in the proportion
      of surface versus intracellular protein, but the contribution of extracellular
      signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway
      activation. As a consequence, inducible membranous PD-L1 expression on SKOV3
      inhibited CD8+ T cell function, and cytoplasmic PD-L1 promoted cancer cell
      growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor
      growth inhibition and demonstrated a potential to decrease the number of PD
      1+CD8+T cells. CONCLUSION: We conclude that TAM induced PD-L1 on the cancer cells
      represents an immune evasion mechanism. The observations confirm the therapeutic
      potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.

PMID- 29055950
TI  - Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.
AB  - The fixed primordial follicles pool theory, which monopolized reproductive
      medicine for more than one hundred years, has been broken by the discovery,
      successful isolation and establishment of ovarian stem cells. It has brought more
      hope than ever of increasing the size of primordial follicle pool, improving
      ovarian function and delaying ovarian consenescence. Traditional view holds that
      stem cell aging contributes to the senility of body and organs. However, in the
      process of ovarian aging, the main factor leading to the decline of the
      reproductive function is the aging and degradation of ovarian stem cell nests,
      rather than the senescence of ovarian germ cells themselves. Recent studies have
      found that the immune system and circulatory system are involved in the formation
      of ovarian germline stem cell niches, as well as regulating the proliferation and
      differentiation of ovarian germline stem cells through cellular and hormonal
      signals. Therefore, we can improve ovarian function and delay ovarian aging by
      improving the immune system and circulatory system, which will provide an updated
      program for the treatment of premature ovarian failure (POF) and infertility.

PMID- 29055951
TI  - Cell Wall-Treated Lactococcus lactis Increases the Plasmid Transfer Efficiency of
      Internal Ribosome Entry Site-Incorporated Lactococcal Bicistronic Vector into DF1
      Cells.
AB  - This study demonstrates that cell wall treatment of Lactococcus lactis harbouring
      the internal ribosome entry site-incorporated lactococcal bicistronic vector
      pNZ:VIG mediated the delivery of genes into an eukaryotic cell line, DF1 cells,
      through bactofection. Bactofection analysis showed that the pNZ:VIG plasmid in L.
      lactis can be transferred into DF1 cells and that both the VP2 and gfp genes
      cloned in the plasmid can be transcribed and translated. The protein band
      relative to the Mr of VP2 protein (49 kDa) was successfully detected via Western
      blot analysis, while green fluorescence was successfully detected using a
      fluorescence microscope. The intensity of the bands detected increased for
      samples treated with both 1.5% (w/v) glycine and 10 MUg/mL of lysozyme when
      compared to L. lactis treated with glycine alone and without treatment. Cell wall
      treatment of L. lactis with a combination of both glycine and lysozyme was not
      only shown to mediate plasmid transfer to DF1 cells, but also to increase the
      plasmid transfer efficiency.

PMID- 29055952
TI  - Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition
      and IK1 Up-Regulation in Rats.
AB  - BACKGROUND/AIMS: High-fat diet (HFD) causes cardiac electrical remodeling and
      increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an
      anthraquinone component isolated from rhubarb and has a similar chemical
      structure with emodin. The protective effect of emodin against cardiac diseases
      has been reported in the literature. However, the cardioprotective property of AE
      is still unknown. The present study investigated the effect of AE on HFD-induced
      QT prolongation in rats. METHODS: Adult male Wistar rats were randomly divided
      into three groups: control, HFD, and AE-treatment groups. Normal diet was given
      to rats in the control group, high-fat diet was given to rats in HFD and AE
      treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats
      were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total
      cholesterol and triglyceride levels were measured to validate the HFD model.
      Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE
      each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp
      technique were applied to examine cardiac electrical activity, action potential
      and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular
      myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of
      Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR
      in vivo and in vitro, respectively. RESULTS: In vivo, AE significantly shortened
      the QT interval, action potential duration at 90% repolarization (APD90) and
      resting membrane potential (RMP), which were markedly elongated by HFD. AE
      increased IK1 current and Kir2.1 protein expression which were reduced in HFD
      rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts
      of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an
      increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. CONCLUSIONS: AE
      prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its
      target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD
      induced cardiac electrical remodeling.

PMID- 29055953
TI  - An Open-Label Randomized Multicenter Study Assessing the Noninferiority of a
      Caffeine-Based Topical Liquid 0.2% versus Minoxidil 5% Solution in Male
      Androgenetic Alopecia.
AB  - BACKGROUND: Androgenetic alopecia is a condition with a high prevalence worldwide
      and affects both males and females. Currently, only 2 approved treatments exist:
      finasteride (males only) and minoxidil 2 or 5% solution (males and females).
      METHODS: We conducted a randomized, open-label, multicenter noninferiority study
      to determine whether a caffeine-based 0.2% topical liquid would be no less
      effective than minoxidil 5% solution in males (n = 210) with androgenetic
      alopecia. The primary end point was the percentage change in the proportion of
      anagen hairs from baseline to 6 months using a frontal and occipital trichogram.
      RESULTS: At 6 months, the group of the 5% minoxidil solution showed a mean
      improvement in anagen ratio of the trichogram of 11.68%, and the group of the
      0.2% caffeine solution had an anagen improvement of 10.59%. The difference of
      mean values between both groups was 1.09%. The statistical analysis was performed
      and reported in accordance with the CONSORT Guidelines 2010 for reporting of
      noninferiority and equivalence randomized trials. CONCLUSION: A caffeine-based
      topical liquid should be considered as not inferior to minoxidil 5% solution in
      men with androgenetic alopecia.

PMID- 29055954
TI  - Artesunate Decreases beta-Catenin Expression, Cell Proliferation and Apoptosis
      Resistance in the MG-63 Human Osteosarcoma Cell Line.
AB  - BACKGROUND: This study aims to determine the effects of artesunate on
      proliferation, apoptosis and beta-catenin expression in the human osteosarcoma
      cell line MG-63. METHODS: MG-63 cells in the logarithmic growth phase were
      collected and cultured with different concentrations of artesunate (12.5 ug/mL,
      25 ug/mL and 50 ug/mL) for 24 h, 48 h and 72 h. The total number of MG-63 cells
      and the morphological changes were observed under an inverted microscope. The MTT
      assay was adopted to test the inhibition rate (IR) of cell growth. The apoptosis
      rate was detected using annexin V/propidium iodide (PI) staining. Cell cycle
      distribution was identified by flow cytometry (FCM), and the expression levels of
      beta-catenin, cyclins and cyclin dependent kinases (CDKs) were measured using
      Western blotting. RESULTS: The results of the MTT assay indicated that artesunate
      could remarkably inhibit MG-63 cell proliferation compared with the rates in the
      untreated control group (0 ug/mL artesunate), and the inhibitory effect was dose
      dependent. The apoptosis rate of MG-63 cells was elevated as the concentration of
      artesunate increased, and all the rates were significantly higher than that in
      the control group. Additionally, as the artesunate concentration increased, the
      proportion of MG-63 cells in G0/G1 phase gradually declined whereas that of cells
      in the G2/M and S phases increased. Western blotting confirmed that a higher
      concentration of artesunate reduced the expression levels of beta-catenin, cyclin
      A, cyclin D1 and CDK1 and increased the expression levels of cyclin B1; however,
      artesunate had no impact on CDK2 expression in MG-63 cells. CONCLUSION: These
      results demonstrated that artesunate can inhibit beta-catenin expression and cell
      proliferation as well as promote cell apoptosis in MG-63 cells, which indicates
      that artesunate may serve as a promising drug in the clinical treatment of
      osteosarcoma.

PMID- 29055955
TI  - LncRNA HANR Promotes Tumorigenesis and Increase of Chemoresistance in
      Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most common cancer
      in the world and the third leading cause of cancer-related death. Critical roles
      for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety
      of cancers, including hepatocellular carcinoma. However, the effect and mechanism
      of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively
      characterized. METHODS: In the current study, we have identified a HCC-expressed
      lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by
      microarray analysis and validated its up-regulated expression by quantitative
      PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and
      functional interactions with HANR. In vivo experiments were performed to assess
      tumorigenesis and increase of chemoresistance. In addition, the HANR expression
      in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was
      constructed to observe the effect of HANR on tumorigenesis and chemoresistance in
      vivo. RESULTS: HANR was demonstrated to be up-regulated in HCC patients and HCC
      cell lines. Increased HANR expression in HCC predicted short survival of
      patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC
      xenograft/orthotopic tumor growth, induced apoptosis and enhanced
      chemosensitivity to doxorubicin, while over-expression of HANR showed the
      opposite effects. It was found that HANR bind to GSKIP for regulating the
      phosphorylation of GSK3beta in HCC. CONCLUSION: Our results demonstrate that HANR
      contributes to the development of HCC and is a promising therapeutic target for
      chemosensitization of HCC cells to doxorubicin, which may represent a promising
      therapeutic target in the future.

PMID- 29055956
TI  - Enhancement of Neural Salty Preference in Obesity.
AB  - BACKGROUND/AIMS: Obesity and high salt intake are major risk factors for
      hypertension and cardiometabolic diseases. Obese individuals often consume more
      dietary salt. We aim to examine the neurophysiologic effects underlying obesity
      related high salt intake. METHODS: A multi-center, random-order, double-blind
      taste study, SATIETY-1, was conducted in the communities of four cities in China;
      and an interventional study was also performed in the local community of
      Chongqing, using brain positron emission tomography/computed tomography (PET/CT)
      scanning. RESULTS: We showed that overweight/obese individuals were prone to
      consume a higher daily salt intake (2.0 g/day higher compared with normal weight
      individuals after multivariable adjustment, 95% CI, 1.2-2.8 g/day, P < 0.001),
      furthermore they exhibited reduced salt sensitivity and a higher salt preference.
      The altered salty taste and salty preference in the overweight/obese individuals
      was related to increased activity in brain regions that included the
      orbitofrontal cortex (OFC, r = 0.44, P= 0.01), insula (r = 0.38, P= 0.03), and
      parahippocampus (r = 0.37, P= 0.04). CONCLUSION: Increased salt intake among
      overweight/obese individuals is associated with altered salt sensitivity and
      preference that related to the abnormal activity of gustatory cortex. This study
      provides insights for reducing salt intake by modifying neural processing of
      salty preference in obesity.

PMID- 29055957
TI  - MiR-1246 Promotes LPS-Induced Inflammatory Injury in Chondrogenic Cells ATDC5 by
      Targeting HNF4gamma.
AB  - BACKGROUND/AIMS: Osteoarthritis (OA) is a common inflammatory joint disease.
      miRNAs are associated with OA and functionally implicated in the pathogenesis of
      the disease. In the present study, we investigated the role of miR-1246 in the
      lipopolysaccharide (LPS)-induced inflammatory injury of ATDC5 cells. METHODS:
      ATDC5 cells were cultured and treated with LPS in a series of concentration (0,
      1, 5, and 10 ug/ml) for 5 h. The cells were transfected with miR-1246-mimic,
      inhibitor, si-HNF4gamma or negative control, then were assessed for cell
      viability using CCK8 assay, apoptosis by flow-cytometry and expressions of miR
      1246 and pro-inflammatory cytokines by qRT-PCR and western blot analysis.
      RESULTS: Cell viability was significantly reduced and cell apoptosis was added in
      ATDC5 cells injured with LPS at the dosage of 5 and 10 ug/ml. Relative mRNA
      expressions of pro-inflammatory cytokines (IL-1beta, IL-6, IL-8 and TNF-alpha)
      were significantly increased. miR-1246 was up-regulated in ATDC5 cells treated
      with LPS. Moreover, miR-1246 overexpression aggravated LPS-induced decrease in
      cell viability, increase in apoptosis and overproduction of pro-inflammatory
      factors. mRNA and protein expressions of HNF4gamma were significantly suppressed
      in cells transfected with miR-124-mimic. Further, miR-1246 knockdown alleviated
      LPS-induced inflammatory injury by up-regulating the expression of HNF4gamma and
      activation of PI3K/AKT and JAK/STAT pathways. CONCLUSIONS: Suppression of miR
      1246 alleviated LPS-induced inflammatory injury in chondrogenic ADTC5 cells by up
      regulation of HNF4gamma and activation of PI3K/AKT and JAK/STAT pathways. The
      findings of this study will provide a novel viewpoint regarding miR-1246 target
      for clinical.

PMID- 29055958
TI  - Streptococcus mutans in Mother-Child Dyads and Early Childhood Caries: Examining
      Factors Underlying Bacterial Colonization.
AB  - This study investigated the association between colonization of mother-child
      dyads with Streptococcus mutans (SM) and early childhood caries (ECC), with
      consideration of the mediator and confounders, using a theoretical model. Four
      hundred mothers and their children from Sao Luis, Brazil, were included in the
      study. A diagram based on directed acyclic graphs was elaborated to analyze the
      association between SM colonization of the mother, mediated by child SM, and ECC.
      Other maternal (socioeconomic, waist circumference, sugar consumption, DMFT
      index, and visible plaque) and child factors (sugar consumption, visible plaque,
      and child age) composed the theoretical model. A total effect model (maternal SM
      on ECC) and a direct effect model, adjusted by the mediation effect of child SM
      (maternal SM via child SM) on ECC, were analyzed. The outcome of interest in this
      study was ECC (number of teeth with caries experience, dmft), which was analyzed
      as a discrete variable by Poisson regression. The Paramed test was used to
      analyze mediation. The following variables were associated with ECC in the total
      effect model: maternal SM, maternal waist circumference >=80 cm, DMFT, maternal
      visible plaque, child age >=4 years, and increased sugar consumption of the child
      (>3 times/day). In the direct effect model, high maternal SM levels remained
      associated with ECC, while moderate and high colonization of the child with SM
      was also associated with ECC. Child SM colonization just partially mediated the
      effect of maternal SM on ECC (33%). Thus, factors other than the mechanism of
      bacterial colonization should be considered in mother-child dyads, including
      eating habits, oral hygiene practices, and a family history of caries.

PMID- 29055959
TI  - Impaired Arginine Metabolism Coupled to a Defective Redox Conduit Contributes to
      Low Plasma Nitric Oxide in Polycystic Ovary Syndrome.
AB  - BACKGROUND: Though oxidative stress is associated with Polycystic Ovary Syndrome
      (PCOS), the status of nitric oxide is still unclear. Nitric Oxide (NO) plays
      pivotal roles in many physiological functions which are compromised in PCOS. Our
      recent study reveals lowered T-regulatory cells (Tregs) in PCOS, and Treg
      generation is known to be regulated by NO levels. However concrete evidences are
      lacking on mechanisms modulating NO levels under PCOS. METHODS: This is a
      retrospective case-control cohort study, comprised of PCOS women (N=29) and
      normal menstruating women as controls (N=20). We analysed NOx (nitrite+nitrate)
      and hydrogen peroxide (H2O2) concentrations, transcript levels of endothelial
      nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and arginine
      modulators, hydrogen peroxide regulators in the cohort. RESULTS: PCOS women
      showed reduced plasma NOx(nitrate+nitrite) and H2O2 compared to controls. We
      report reduction in transcript levels of iNOS/NOS2 and eNOS/NOS3 in PCOS
      peripheral blood. The transcripts involved in arginine bioavailability:
      Argininosuccinate lyase (ASL), Solute Carrier Family1, member 7 (SLC7A1) and
      Arginase 1 (ARG1) and Asymmetric Dimethyl Arginine (ADMA) metabolism: Protein
      arginine methyltransferase 1 (PRMT1) and Dimethylarginine dimethylaminohydrolase
      2 (DDAH2) also showed differential expression. H2O2 concentration in PCOS women
      was also found to be reduced. The reduction can be attributed to increase in
      catalase levels as a consequence of the body's effort to alleviate the oxidative
      burden in the system. CONCLUSION: Our study advocates that PCOS women have
      lowered NO due to reduced iNOS/eNOS expression, low H2O2, high ADMA synthesis and
      reduced arginine bioavailability. An in-depth analysis of redox biology of PCOS
      to open up potential therapeutic strategies is highly recommended.

PMID- 29055961
TI  - Plac1 Expression Pattern at the Mouse Fetomaternal Interface and Involvement in
      Trophoblast Differentiation.
AB  - BACKGROUND/AIMS: It is well known that Plac1 is a placenta-specific gene;
      however, its spatiotemporal expression pattern and exact role at t h e mouse
      fetomaternal interface r e m a i n s unclear. METHODS: In situ hybridization
      (ISH) was used to localize the Plac1 mRNA at the mouse fetomaternal interface. A
      trophoblast stem cell (TS) differentiation model with Plac1 shRNA-overexpressing
      lentivirus was employed to investigate the possible role of Plac1 in
      placentation. Real-time RT-PCR was used to detect changes in gene expression.
      RESULTS: Plac1 was exclusively expressed in the ectoplacental cone (EPC) as well
      as in 8.5 and 9.5 days post-coitum (dpc) embryos. Subsequently, Plac1 expression
      was abundant in the spongiotrophoblast layer and moderately in the labyrinth
      layer until 13.5 dpc, and declined thereafter. Interestingly, Plac1 was also
      expressed by secondary trophoblast giant cells and glycogen trophoblast cells,
      but not in primary trophoblast giant cells. Plac1 transcription was increased
      during the TS differentiation (P < 0.01), and knockdown of Plac1 significantly
      impaired TS differentiation. CONCLUSION: Plac1 is abundantly expressed at the
      fetomaternal interface and in all trophoblast subtypes except in primary
      trophoblast giant cells. Plac1 knockdown retarded the progress of TS
      differentiation, indicating that Plac1 is necessary for normal trophoblast
      differentiation into various trophoblast subpopulations.

PMID- 29055960
TI  - MicroRNA-145 Aggravates Hypoxia-Induced Injury by Targeting Rac1 in H9c2 Cells.
AB  - BACKGROUND/AIMS: Myocardial infarction (MI) is a leading cause of morbidity and
      mortality. Here, we sought to explore the potential role and underlying mechanism
      of miR-145 in MI. METHODS: H9c2 cells were cultured under persistent hypoxia to
      simulate MI. The hypoxia-induced injury was assessed on the basis of cell
      viability, migration, invasion and apoptosis. The expression of miR-145 was
      evaluated by qRT-PCR and the influence of aberrantly expressed miR-145 on H9c2
      cells under hypoxia was also estimated. Utilizing bioinformatics methods, the
      target genes of miR-145 were verified by luciferase reporter assay. Then, effects
      of abnormally expressed target gene on miR-145 silenced H9c2 cells were assessed.
      Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3
      kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK)/extracellular
      signal-regulated kinase (ERK) pathways were detected by Western blot analysis.
      RESULTS: Hypoxia remarkably lowered viability, migration and invasion but
      promoted cell apoptosis. Meantime, the miR-145 level was up-regulated in H9c2
      cells under hypoxia. Following experiments suggested that hypoxia-induced injury
      was exacerbated by miR-145 overexpression while was alleviated by miR-145
      silence. Rac1 was predicted and further validated to be a target gene of miR-145.
      The influence of miR-145 silencing on H9c2 cells under hypoxia could be reversed
      by down-regulation of Rac1. Additionally, the phosphorylation levels of PI3K,
      AKT, MAPK and ERK were all elevated in miR-145 silenced cells and these
      alterations were reversed by down-regulation of Rac1. CONCLUSION: miR-145
      silencing could protect H9c2 cells against hypoxia-induced injury by targeting
      Rac1, in which PI3K/AKT and MAPK/ERK pathways might be involved.

PMID- 29055963
TI  - A fatal case of acute bentazone overdose despite cricothyroidotomy during
      cardiopulmonary resuscitation.
AB  - Bentazone is classified as a moderately hazardous (class II) herbicide by the
      World Health Organization. A 53-year-old Korean woman was transferred to the
      emergency department after a suicide attempt using approximately 500 mL of
      bentazone one hour prior to admission. Upon admission, she was alert and
      tachycardia of 125/min was observed. She was treated with gastric lavage and
      activated charcoal, during which she experienced diarrhea. Two hours after
      bentazone ingestion, cardiac arrest and muscle rigidity throughout the body
      occurred. Cardiopulmonary resuscitation was immediately started. Endotracheal
      intubation after administration of a muscle relaxant (succinylcholine) was
      unsuccessful because of temporomandibular joint muscle rigidity. Surgical
      cricothyroidotomy was performed by the emergency physician, but the patient was
      not resuscitated. For cardiac arrest patients with muscle rigidity caused by
      bentazone overdose, endotracheal intubation may be challenging because of muscle
      rigidity, despite appropriate use of muscle relaxants. Early surgical
      cricothyroidotomy may be the preferred method of airway management in these
      patients.

PMID- 29055962
TI  - Can clinical scoring systems improve the diagnostic accuracy in patients with
      suspected adult appendicitis and equivocal preoperative computed tomography
      findings?
AB  - OBJECTIVE: Adult appendicitis (AA) with equivocal computed tomography (CT)
      findings remains a diagnostic challenge for physicians. Herein we evaluated the
      diagnostic performance of several clinical scoring systems in adult patients with
      suspected appendicitis and equivocal CT findings. METHODS: We retrospectively
      evaluated 189 adult patients with equivocal CT findings. Alvarado, Eskelinen,
      appendicitis inflammatory response, Raja Isteri Pengiran Anak Saleha Appendicitis
      (RIPASA), and adult appendicitis score (AAS) scores were evaluated, receiver
      operating characteristic analysis was conducted, and the optimal, low, and high
      cut-off values were determined for patient classification into three groups: low,
      intermediate, or high. RESULTS: In total, 61 patients were included in the
      appendicitis group and 128 in the non-appendicitis group. There were no
      significant differences between the area under the curve of the clinical scoring
      systems in the final diagnosis of AA for equivocal appendicitis on CT (Alvarado,
      0.698; Eskelinen, 0.710; appendicitis inflammatory response, 0.668; RIPASA,
      0.653; AAS, 0.726). A RIPASA score greater than 7.5 had a high positive
      predictive value (90.9) and an AAS score less than or equal to 5 had a high
      negative predictive value (91.7) in the diagnosis of AA. CONCLUSION: The accuracy
      of clinical scoring systems in the diagnosis of AA with equivocal CT findings was
      moderate. Therefore, a high RIPASA score may assist in the diagnosis of AA in
      patients with equivocal CT findings, and a low AAS score may be used as a
      criterion for patient discharge. Most patients presented with intermediate
      scores. The patients with equivocal CT findings may be considered as a third
      diagnostic category of AA.

PMID- 29055964
TI  - The Safety of Percutaneous Trigger Digit Release Increased by Neurovascular
      Displacement with Local Hydraulic Dilatation: An Anatomical and Clinical Study.
AB  - BACKGROUND Although percutaneous trigger digit release is common, controversy
      exists regarding its safety. The purpose of this study was to evaluate the
      feasibility and safety of the neurovascular displacement by local hydraulic
      dilatation (LHD) during percutaneous trigger digit release. MATERIAL AND METHODS
      Ten cadaver hands with 50 digits were dissected in this anatomical study. The
      distance between bilateral neurovascular bundles in each digit was measured
      before LHD and after LHD. The difference between the measured data before LHD and
      those after LHD in the same digit was compared to assess the feasibility of the
      neurovascular displacement by LHD. A further 81 patients with 106 trigger digits
      were treated by percutaneous release with neurovascular displacement by LHD in
      our clinical series. All patients were followed for 12 months. During the follow
      up period, the presence of any postoperative complication and patient
      satisfaction were recorded. RESULTS In our anatomical study, there was a
      statistically significant difference (p<0.05) comparing the average distance of
      bilateral neurovascular bundles before LHD with that after LHD. In the current
      series, no complications, such as digital neurovascular injury or recurrence of
      trigger, were encountered. On subjective assessment, 80/81 patients (98.8%) with
      105/106 digits (99.1%) were graded as satisfactory with complete resolution of
      symptoms by percutaneous release under LHD. CONCLUSIONS Based on our study
      anatomical and clinical results, the neurovascular displacement by LHD may be a
      feasible adjunctive technique that may play a role in increasing the safety of
      percutaneous trigger digit release.

PMID- 29055965
TI  - Short-Term High-Dose Steroid Therapy in a Case of Rhabdomyolysis Refractory to
      Intravenous Fluids.

PMID- 29055966
TI  - Comparison between unilateral PNIF and rhinomanometry in the evaluation of nasal
      cycle.
AB  - BACKGROUND: Human unilateral nasal airflow shows spontaneous changes over a
      period of hours due to the alternating congestion and decongestion of the venous
      sinuses within the nasal turbinates and nasal septum. The aim of the present
      study was to compare PNIF and unilateral PNIF with nasal resistances measured by
      means of AAR in the evaluation of the nasal cycle. METHODS: PNIF, unilateral PNIF
      and AAR measurements were randomly performed in 20 non-smokers, non-asthmatic
      volunteers, with a SNOT 22 score lower than 1. Nasal measurements were done four
      times in a single day at 08.30, 11.00, 13.30 and 16.00. The correlation between
      PNIF, unilateral PNIF and nasal resistances was studied. The pattern of nasal
      airflow for each subject was also analyzed. RESULTS: A significant negative
      correlation between PNIF-lPNIF-rPNIF and respectively AAR-lAAR-rAAR was found.
      Only 1 subject did not show nasal cycle, while all the rest were equally
      distributed between a reciprocal pattern of the nasal cycle, or an in-phase
      changes of the nasal cycle, both at PNIF and AAR. CONCLUSIONS: Nasal cycle can be
      easily assessed by means of PNIF. In fact, AAR and PNIF showed a reasonable
      correlation in the measurement of nasal cycle, although PNIF offered a lower
      variability. Reciprocal and in-phase patterns of the nasal cycle were equally
      distributed in our population.

PMID- 29055967
TI  - Reductive evolution in outer membrane protein biogenesis has not compromised cell
      surface complexity in Helicobacter pylori.
AB  - Helicobacter pylori is a gram-negative bacterial pathogen that chronically
      inhabits the human stomach. To survive and maintain advantage, it has evolved
      unique host-pathogen interactions mediated by Helicobacter-specific proteins in
      the bacterial outer membrane. These outer membrane proteins (OMPs) are anchored
      to the cell surface via a C-terminal beta-barrel domain, which requires their
      assembly by the beta-barrel assembly machinery (BAM). Here we have assessed the
      complexity of the OMP C-terminal beta-barrel domains employed by H. pylori, and
      characterized the H. pyloriBAM complex. Around 50 Helicobacter-specific OMPs were
      assessed with predictive structural algorithms. The data suggest that H. pylori
      utilizes a unique beta-barrel architecture that might constitute H. pylori
      specific Type V secretions system. The structural and functional diversity in
      these proteins is encompassed by their extramembrane domains. Bioinformatic and
      biochemical characterization suggests that the low beta-barrel-complexity
      requires only minimalist assembly machinery. The H. pylori proteins BamA and BamD
      associate to form a BAM complex, with features of BamA enabling an
      oligomerization that might represent a mechanism by which a minimalist BAM
      complex forms a larger, sophisticated machinery capable of servicing the outer
      membrane proteome of H. pylori.

PMID- 29055970
TI  - Low estrogen but not high cholesterol induced suicide?

PMID- 29055969
TI  - Asymmetry in the Cortical and Trabecular Bone of the Human Humerus During
      Development.
AB  - Many studies have noted that the bones of the human upper limb display bilateral
      asymmetry, commonly linking this asymmetry in external and internal morphology to
      handedness and lateralization. Few studies, however, have attempted to track
      asymmetry throughout ontogeny. This study assesses the ontogenetic development of
      cortical and trabecular bone asymmetry in the humerus. We predict that
      directional asymmetry in structural properties will emerge in concert with hand
      preference and increased activity levels during the juvenile period. Paired
      humeri from 57 individuals from the Norris Farms #36 archaeological skeletal
      collection ranging in age from neonate to adult were used in the current study.
      Cortical bone cross-sectional properties and three-dimensional trabecular bone
      structure were quantified from microcomputed tomography data. The results
      indicate significant absolute asymmetry in all measured cortical and trabecular
      bone variables across all ages. Trabecular bone displays significantly higher
      absolute asymmetry than cortical bone. Contrary to expectations, however, this
      study found very little evidence for significant directional asymmetry in humeral
      length and cortical or trabecular bone variables, except in adults. The presence
      of significant absolute asymmetry in all age groups, and the lack of significant
      directional asymmetry in almost all variables at all ages, suggests that
      structural differences due to higher levels of habitual loading in the dominant
      arm are overlain on a template of potentially significant existing asymmetry.
      Anat Rec, 301:1012-1025, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29055968
TI  - Identification of hereditary cancer in the general population: development and
      validation of a screening questionnaire for obtaining the family history of
      cancer.
AB  - One of the challenges for Latin American countries is to include in their
      healthcare systems technologies that can be applied to hereditary cancer
      detection and management. The aim of the study is to create and validate a
      questionnaire to identify individuals with possible risk for hereditary cancer
      predisposition syndromes (HCPS), using different strategies in a Cancer
      Prevention Service in Brazil. The primary screening questionnaire (PSQ) was
      developed to identify families at-risk for HCPS. The PSQ was validated using
      discrimination measures, and the reproducibility was estimated through kappa
      coefficient. Patients with at least one affirmative answer had the pedigree drawn
      using three alternative interview approaches: in-person, by telephone, or letter.
      Validation of these approaches was done. Kappa and intraclass correlation
      coefficients were used to analyze data's reproducibility considering the presence
      of clinical criteria for HCPS. The PSQ was applied to a convenience sample of
      20,000 women of which 3121 (15.6%) answered at least one affirmative question and
      1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores
      of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree
      drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and
      letter approaches, respectively. Pedigree analysis allowed us to identify 465
      individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ
      fulfills its function, allowing the identification of HCPS at-risk families. The
      use of alternative screening methods may reduce the number of excluded at-risk
      individuals/families who live in locations where oncogenetic services are not
      established.

PMID- 29055971
TI  - Luck, come here! Automatic approach tendencies toward gambling cues in moderate-
      to high-risk gamblers.
AB  - BACKGROUND AND AIMS: Similar to substance addictions, reward-related cognitive
      motivational processes, such as selective attention and positive memory biases,
      have been found in disordered gambling. Despite findings that individuals with
      substance use problems are biased to approach substance-related cues
      automatically, no study has yet focused on automatic approach tendencies for
      motivationally salient gambling cues in problem gamblers. We tested if moderate-
      to high-risk gamblers show a gambling approach bias and whether this bias was
      related prospectively to gambling behaviour and problems. DESIGN: Cross-sectional
      assessment study evaluating the concurrent and longitudinal correlates of
      gambling approach bias in moderate- to high-risk gamblers compared with non
      problem gamblers. SETTING: Online study throughout the Netherlands. PARTICIPANTS:
      Twenty-six non-treatment-seeking moderate- to high-risk gamblers and 26 non
      problem gamblers community-recruited via the internet. MEASUREMENTS: Two online
      assessment sessions 6 months apart, including self-report measures of gambling
      problems and behaviour (frequency, duration and expenditure) and the gambling
      approach avoidance task, with stimuli tailored to individual gambling habits.
      FINDINGS: Relative to non-problem gamblers, moderate- to high-risk gamblers
      revealed a stronger approach bias towards gambling-related stimuli than neutral
      stimuli (P = 0.03). Gambling approach bias was correlated positively with past
      month gambling expenditure at baseline (P = 0.03) and with monthly frequency of
      gambling at follow-up (P = 0.02). In multiple hierarchical regressions, baseline
      gambling approach bias predicted monthly frequency positively (P = 0.03) and
      total duration of gambling episodes (P = 0.01) 6 months later, but not gambling
      problems or expenditure. CONCLUSIONS: In the Netherlands, relative to non-problem
      gamblers, moderate- to high-risk gamblers appear to have a stronger tendency to
      approach rather than to avoid gambling-related pictures compared with neutral
      ones. This gambling approach bias is associated concurrently with past-month
      gambling expenditure and duration of gambling and has been found to predict
      persistence in gambling behaviour over time.

PMID- 29055972
TI  - Chronic obstructive pulmonary disease and beta-blocker treatment in Asian
      patients with heart failure.
AB  - AIMS: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are
      increasingly frequent in Asia and commonly coexist in patients. However, the
      prevalence of COPD among Asian patients with HF and its impact on HF treatment
      are unclear. METHODS AND RESULTS: We compared clinical characteristics and
      treatment approaches between patients with or without a history of COPD, before
      and after 1:2 propensity matching (for age, sex, geographical region, income
      level, and ethnic group) in 5232 prospectively recruited patients with HF and
      reduced ejection fraction (HFrEF, <40%) from 11 Asian regions (Northeast Asia:
      South Korea, Japan, Taiwan, Hong Kong, and China; South Asia: India; Southeast
      Asia: Thailand, Malaysia, Philippines, Indonesia, and Singapore). Among the 5232
      patients with HFrEF, a history of COPD was present in 8.3% (n = 434), with
      significant variation in geography (11.0% in Northeast Asia vs. 4.7% in South
      Asia), regional income level (9.7% in high income vs. 5.8% in low income), and
      ethnicity (17.0% in Filipinos vs. 5.2% in Indians) (all P < 0.05). Use of
      mineralocorticoid receptor antagonists and diuretics was similar between groups,
      while usage of all beta-blockers was lower in the COPD group than in the non-COPD
      group in the overall (66.3% vs. 79.9%) and propensity-matched cohorts (66.3% vs.
      81.7%) (all P < 0.05). A striking exception was the Japanese cohort in which beta
      blocker use was high in COPD and non-COPD patients (95.2% vs. 91.2%).
      CONCLUSIONS: The prevalence of COPD in HFrEF varied across Asia and was related
      to underuse of beta-blockers, except in Japan.

PMID- 29055973
TI  - Characterisation of corn extrudates with the addition of brewers' spent grain as
      a raw material for the production of functional batters.
AB  - BACKGROUND: Novel food batters, recommended for various products, are at present
      manufactured by extru- sion. Thanks to this, it is possible to look for and
      process new raw materials, if their processing has so far been considered
      impossible or economically unviable. The purpose of the work was therefore to
      investigate the extrudates produced from the corn and brewers' spent grain
      compounds that are subsequently used as raw material for food batter production.
      METHODS: The work presents the findings of research on extrusion of corn mixes
      with varying levels of brewers' spent grains, to the maximum amount of 30%. Tests
      were conducted using a co-rotating double screw extruder, equipped with a single
      outlet matrix with a diameter of 2.5mm. The products obtained were subjected to
      analysis of their parameters (apparent density, strength parameters, abrasiveness
      index) and the granulation of a single fraction was checked. The sample for which
      the percentage content was the highest was subjected to a detailed analysis of
      particle shape using vision software. RESULTS: It was found that an increase in
      the content of brewers' spent grains resulted in increased hardness of the
      products obtained. During the tests it was observed that the increasing hardness
      of the measured sam- ples is opposite to their abrasion resistance. The maximum
      decrement of the brasion parameters was seen for extrudates with 30% spent grain
      addition and was 1.4%, while the minimum decrement values for extrudates with
      brewers' grain content (10%) amounted to 0.85%. It was noted that this may prove
      the high brittleness of such products, particularly on the outer surface. It was
      also observed that lower grindability was recorded for samples produced by
      extrusion at a temperature of 140 degrees C. On the other hand, higher
      grindability obtained at a temperature of 120 degrees C may facilitate the
      grinding of such products, which may be particularly important in the production
      of food batter. CONCLUSIONS: Brewers' spent grains used as an addition to corn
      groats contribute to substantial changes in the extrudates obtained. It is also
      possible to produce compact extrudates with a brewers' spent grain content of
      30%. After grinding, extrudates with higher brewers' spent grain content are
      distinguished by more rounded grains. The packing index of the samples indicates
      the increased accuracy of covering products with such batter, which indicates an
      advantage of food batters containing brewers' spent grains.

PMID- 29055974
TI  - Technology development of protein rich concentrates for nutrition in extreme
      conditions using soybean and meat by-products.
AB  - BACKGROUND: There is a need to develop new foods for participants of expeditions
      in extreme conditions, which must be self-sufficient. These foods should be light
      to carry, with a long shelf life, tasty and with  high nutrient density.
      Currently, protein sources are limited mainly to dried and canned meat. In this
      work, a protein-rich dried concentrate suitable for extreme expeditions was
      developed using soya, tomato, milk whey and meat by-products. METHODS: Protein
      concentrates were developed using minced beef liver and heart, dehydrated and
      mixed with a soya protein-lycopene coagulate (SPLC) obtained from a solution
      prepared with germi- nated soybeans and mixed with tomato paste in milk whey, and
      finally dried. The technological parameters of pressing SPLC and of drying the
      protein concentrate were optimized using response surface methodology. RESULTS:
      The optimized technological parameters to prepare the protein concentrates were
      obtained, with 70:30 being the ideal ratio of minced meat to SPLC. The developed
      protein concentrates are characterized by a high calorific value of 376 kcal/100
      g of dry product, with a water content of 98 g.kg-1, and 641-644 g.kg-1 of
      proteins. The essential amino acid indices are 100, with minimum essential amino
      acid content constitut- ing 100-128% of the FAO standard, depending on the raw
      meat used. These concentrates are also rich in micronutrients such as beta
      carotene and vitamin C. CONCLUSIONS: Analysis of the nutrient content showed that
      these non-perishable concentrates present a high nutritional value and complement
      other widely available vegetable concentrates to prepare a two-course meal. The
      soups and porridges prepared with these concentrates can be classified as
      functional foods, and comply with army requirements applicable to food products
      for extreme conditions.

PMID- 29055975
TI  - Changes in the level and antioxidant activity of polyphenols during storage of
      enzymatically treated raspberry juices and syrups.
AB  - BACKGROUND: Berry juices are a rich source of phenolic compounds exhibiting
      antioxidant activity. Unfortu- nately, polyphenols and especially anthocyanins
      are degraded during storage. METHODS: The levels of total phenolic compounds,
      phenolic acids, flavonoids, and antho- cyanins as well as antioxidant activity
      (radical scavenging ability against DPPH and ABTS+* and chelating power Fe2+)
      were determined in raspberry juices (obtained after enzymatic treatment with
      three commercial pectinolytic enzyme preparations) and syrups (obtained by the
      addition of sucrose at concentrations of 30% and 70%) during storage. RESULTS:
      During the five-month storage of juices and syrups at room temperature, there was
      significant re- duction in the level of phenolic compounds, in particular
      anthocyanins (up to 95% in relation to the initial content). Storage of raspberry
      juices and syrups also resulted in a reduction in antioxidant activity.
      CONCLUSIONS: The enzymatic treatment of the raspberry mash generally increased
      the losses of anthocyanins. The addition of sugar to fruit juices only slightly
      reduced these losses.

PMID- 29055976
TI  - The influence of microwave cooking on the nutritional composition and antioxidant
      activity of the underutilized perah seed.
AB  - BACKGROUND: Perah seed is one of the most underutilized oilseeds, containing high
      nutritional values and high percentage of alpha-linoleneic acid, which may have a
      high potential in food and pharmaceutical applica- tions. The main objective of
      this study was to evaluate the influence of microwave (MW) cooking on the
      proximate composition and antioxidant activity of perah seeds. METHODS: In this
      study, the proximate composition and amygdalin concentration of MW ir- radiated
      perah seeds were determined. The total phenolic content (TPC), Maillard reaction
      products (MRPs) and antioxidant activity of methanol (PME), 70% methanol in water
      (PMW), ethanol (PEE), 70% ethanol  in water (PEW) extracts and methanol extract
      of oil (PMO) were evaluated during MW cooking. The anti- oxidant activity was
      evaluated using multiple assays, namely DPPH radical scavenging activity, beta
      Carotene bleaching assay, and reducing power. RESULTS: Microwave cooking did not
      significantly increase crude lipid and carbohydrate content, and the amounts of
      other nutrients such as ash, crude protein and fibre remained almost unchanged.
      As evaluated  by HPLC, the amygdalin concentration in the seeds was reduced by MW
      cooking. The TPC, MRP and anti- oxidant activity of the solvent extracts of perah
      seeds increased significantly with increasing roasting time. Of all the extracts,
      PMW at all MW cooking times displayed the highest antioxidant effectiveness.
      However, thermal treatment significantly reduced the antioxidant properties of
      PMO. The values for TPC, MRP and antioxidant effectiveness of the samples were
      ranked in the following order: PMW > PEW > PME > PEE > PMO, in both control and
      microwaved samples. CONCLUSIONS: In determining the overall quality of the
      products, MW cooking time was found to be a critical factor. Solubilization of
      phenolic compounds and formation of MRPs during MW cooking could have caused the
      increase in antioxidant activity of the perah seeds.

PMID- 29055977
TI  - Roasting pumpkin seeds and changes in the composition and oxidative stability of
      cold-pressed oils.
AB  - BACKGROUND: Pumpkin seed oil is valuable oil for its distinctive taste and aroma,
      as well as supposed health- promoting properties. The aim of this study was to
      investigate how roasting pumpkin seeds influences the physicochemical properties
      of cold-pressed oils. METHODS: The fatty acid composition, content of
      phytosterols, carotenoids and tocopherols, oxidative stability and colour were
      determined in oils after cold pressing and storage for 3 months using GC-FID,
      GCxGC-ToFMS, HPLC, Rancimat and spectrophotometric methods. RESULTS: The results
      of this study indicate that the seed-roasting and storage process have no effect
      on the fatty acid composition of pumpkin seed oils, but does affect phytosterols
      and tocopherols. The carotenoid content decreased after storage. The colour of
      the roasted oil was darker and changed significantly during storage. CONCLUSIONS:
      Pumpkin oil obtained from roasted seeds shows better physicochemical properties
      and oxidative stability than oil from unroasted seeds.

PMID- 29055978
TI  - Determining the prevalence of inv-positive and ail-positive Yersinia
      enterocolitica in pig tonsils using PCR and culture methods.
AB  - BACKGROUND: Yersiniosis is believed to be the third most common intestinal
      zoonosis in the European Union, after campylobacteriosis and salmonellosis.
      Yersinia enterocolitica is the most common species responsible for human
      infections. Pigs are regarded as the biggest reservoir of pathogenic Y.
      enterocolitica strains, which are mainly isolated from pig tonsils. The aim of
      this paper is to examine the prevalence of inv-positive and ail-positive Y.
      enterocolitica in pigs which were slaughtered in a Polish abattoir. METHODS: Real
      time PCR and culture methods were used to assess the prevalence of patho- genic
      Y. enterocolitica strains in pig tonsils. Real-time PCR was applied to detect inv
      positive and ail-positive Y. enterocolitica. Y. enterocolitica was also isolated
      by applying direct plating, unselective (tryptic soy broth) and selective
      (irgasan-ticarcillin-potassium chlorate bouillon) enrichment. RESULTS: A total of
      180 pigs were studied, of which 85% and 32% respectively were found to be
      infected with inv-positive and ail-positive Y. enterocolitica. The 92 inv
      positive and ail-positive isolates, from 57 culture- positive tonsils, underwent
      bio- and serotyping. The most common was bioserotype 4/O:3, which was found in 53
      (93%) out of 57 culture-positive tonsils. Strains of bioserotypes 2/O:5, 2/O:9
      and 2/O:5.27 occurred in significantly lower numbers. CONCLUSIONS: The prevalence
      of inv-positive and ail-positive Y. enterocolitica was found to be high in the
      ton- sils of slaughtered pigs, using real-time PCR. The real-time PCR method for
      the detection and identification of pathogenic Y. enterocolitica is sensitive and
      specific, which has been verified by specificity and sensitivity tests using the
      pure cultures. Serotypes were distinguished from each other using PCR serotyping.
      The PCR method was essential in forming our conclusions.

PMID- 29055980
TI  - A comparison of two methods of determining colour change in the assessment of the
      quality of pork.
AB  - BACKGROUND: The colour of pork is one of the most important measures of meat
      quality. For the consumer, it is a sign of freshness, crucial for the decision to
      buy a product. The storage of meat results in constant col- our changes.
      Differences can be found in all colour parameters, especially chromatic ones,
      such as redness (a*) and hue angle (h degrees ), as these changes are
      significantly correlated with a number of quality traits. Colour change can be
      determined not only by evaluating changes in colour parameters, but also by
      establishing the change in absorbance of specific wavelengths of light. The aim
      of this study was to compare the usefulness of these two methods of determining
      colour change: parameters measured on the CIELAB and CIELCh scales and colour
      change (%CC) determined based on the absorbance of selected wavelengths of light,
      i.e. 505, 540, 560, 580 and 630 nm. In this paper, we analysed two methods of
      measuring colour change in terms of their relevance for meat quality assessment.
      METHODS: The study involved 150 samples of the longissimus lumborum muscle
      collected from 150 carcasses of pigs slaughtered on an industrial line, weighing
      65-107 kg, with an average carcass weight of 86.1 kg. Meat sensory analysis
      (colour, wateriness, firmness), physicochemical assessment (colour, WHC, pH48)
      and proximate analysis (moisture, total protein, fat, ash) were carried out. The
      methods included the determination of (I) changes in colour parameters measured
      on the CIELAB and CIELCh scales, and (II) colour change (%CC) based on the
      absorbance of selected wavelengths: 505, 540, 560, 580 and 630 nm. Chromatic
      absorbance values of a wavelength of 525 nm (A525p) and the relative content of
      Mb, MbO2 and MetMb were calculated according to the method proposed by Krzywicki
      (1979). RESULTS: Basic chemical composition - with few exceptions - was not
      significantly correlated with differenc- es in the values of colour parameters
      (DeltaL*, ?a*, ?b*, DeltaC*, Deltah degrees ) and colour change (%CC). With an
      increase in scores in the sensory evaluation of colour, wateriness, and firmness,
      and an increase in WHC and pH48, the differences in lightness (DeltaL*)
      significantly increased and differences in chromatic value (?a*, ?b*, DeltaC*,
      Deltah degrees ) and %CC decreased, for all tested combinations of wavelengths.
      The highest correlation coefficients were observed for ?a* and Deltah degrees 
      and %CC540/630 and %CC580/630, with colour change (%CC540/630 and %CC580/630)
      showing a stronger correlation with the tested meat quality traits than the
      differences in redness (?a*) and hue angle (Deltah degrees ). We found a very
      strong correlation between changes in the relative levels of MetMb (DeltaMetMb)
      and colour change (%CC) based on the absorbance of wavelengths of 540 and 505 nm,
      and 580 and 505 nm (r = 0.950*** and r = 0.967***, respectively). CONCLUSIONS:
      The determination of colour change based on the absorbance of two combinations of
      wave- lengths, i.e. (I) 540 and 630, and (II) 580 nm and 630 nm, is more useful
      in the assessment of pork quality than changes in two most relevant parameters of
      the CIELAB and CIELCh scales, i.e. redness (Deltaa*) and hue angle (Deltah
      degrees ). Moreover, the determination of absorbance of a wavelength of 630 nm
      was more useful for determin- ing colour change (%CC) than 505 nm. Colour change
      (%CC) based on the absorbance of wavelengths of 540 and 505 nm and 580 and 505 nm
      reflect the changes in the relative amounts of MetMb very well.

PMID- 29055979
TI  - Investigating the effect of aqueous extracts of basil and savory on antioxidant
      activity, microbial and sensory properties of probiotic yogurt.
AB  - BACKGROUND: The low viability of probiotics causes the short shelf life of
      fermented products. Therefore compounds which prolong the viability of probiotic
      bacteria can increase or at least maintain the health- benefiting properties of
      these products. On the other hand, the addition of antioxidants is one of the
      methods to increase the shelf life of food products which has recently become
      more prevalent. In this respect, herbal extracts which are a good source of
      antioxidants can be appropriate alternative. The aim of this study was  to
      evaluate the effect of adding basil and savory extracts on antioxidant activity,
      and on the microbial and organoleptic characteristics of probiotic yogurt.
      METHODS: The effect of adding basil extract (8% and 10%) and savory extract (6%
      and 8%) separately to low fat yogurt (1.5% fat) containing Lactobacillus
      paracasei subsp. paracasei was investigated. The samples were stored at 4 degrees
      C. The viability of Lactobacillus paracasei subsp. paracasei, antioxidant activ-
      ity and sensory properties of probiotic yogurt were evaluated on the 1st, 7th,
      14th and 21st days. RESULTS: Basil and savory extracts significantly increased
      the viability of probiotic bacteria (p < 0.05). Dur- ing storage, probiotic
      counts markedly decreased (p < 0.05) in comparison to the control sample. The
      addi- tion of herbal extracts significantly increased antioxidant activity, but
      this activity decreased during storage (p < 0.05). The scores for taste, odor,
      color and overall acceptance decreased as herbal extracts increased, but there
      was no significant difference between the test samples and control sample in
      terms of the texture score (p > 0.05). During storage, there was no significant
      difference between the organoleptic scores of the samples (p > 0.05), but the
      taste score did increase significantly (p < 0.05). CONCLUSIONS: It can be
      concluded that adding herbal extracts had a positive effect on the viability of
      probiotics and antioxidant activity of probiotic yogurt.

PMID- 29055981
TI  - Nutritional values and metabolic profile with and without boiled treatment of
      'Gallo Matese' beans (Phaseolus vulgaris L.), a landrace from Southern Italy.
AB  - BACKGROUND: 'Gallo Matese' beans are known as a typical legume of Southern Italy
      and continue to be consumed as a traditional food preserving the diversity of
      this region. Nonetheless, no information about the nutritional values of this
      legume is available. The objective of the present investigation was to determine
      the nutritional value and metabolic profile of 'Gallo Matese' beans. Results.
      'Gallo Matese' beans contain high levels of proteins (22.64 g/100 g) and
      essential amino acids  (8.3 g/100 g). Furthermore, differentunsaturated fatty
      acidscontributetothetotalamountoflipids (0.97 g/100 g); among them, the essential
      PUFA alpha-linolenic (0.48 g/100 g) and linoleic (0.39 g/100 g) acids are the
      most abundant. The total phenol content was revealed and ABTS and ORAC
      fluorescein methods were applied to determine the radical scavenging capabilities
      of the extract with and without boiled treatment. Finally, a de- crease in
      trypsin and chymotrypsin inhibitory activities was estimated before and after the
      boiling procedure. Conclusion. The data obtained show that 'Gallo Matese' beans
      are a functional food with healthy qualities. Overall, these results are useful
      to promote their cultivation and consumption, thus preserving Italian beans
      biodiversity due to consumer interest in choosing a healthy diet, such as the
      Mediterran. METHODS: nd. 'Gallo Matese' beans are known as a typical legume of
      Southern Italy and continue to be consumed as a traditional food preserving the
      diversity of this region. Nonetheless, no information about the nutritional
      values of this legume is available. The objective of the present investigation
      was to determine the nutritional value and metabolic profile of 'Gallo Matese'
      beans. RESULTS: 'Gallo Matese' beans contain high levels of proteins (22.64 g/100
      g) and essential amino acids  (8.3 g/100 g). Furthermore, differentunsaturated
      fatty acidscontributetothetotalamountoflipids (0.97 g/100 g); among them, the
      essential PUFA alpha-linolenic (0.48 g/100 g) and linoleic (0.39 g/100 g) acids
      are the most abundant. The total phenol content was revealed and ABTS and ORAC
      fluorescein methods were applied to determine the radical scavenging capabilities
      of the extract with and without boiled treatment. Finally, a de- crease in
      trypsin and chymotrypsin inhibitory activities was estimated before and after the
      boiling procedure. CONCLUSIONS: The data obtained show that 'Gallo Matese' beans
      are a functional food with healthy qualities. Overall, these results are useful
      to promote their cultivation and consumption, thus preserving Italian beans
      biodiversity due to consumer interest in choosing a healthy diet, such as the
      Mediterranean diet.

PMID- 29055982
TI  - Vitamin A status and its determinants in patients with cystic fibrosis.
AB  - BACKGROUND: Routine administration of vitamin A, recommended in CF patients, can
      help to prevent its deficiency. However, high vitamin A supplementation may lead
      to its excessive level and possible toxicity. Therefore, the aim of the present
      study was to assess the status of vitamin A and the determinants of its body
      resources in CF patients. METHODS: In 196 CF patients aged from 4 months to 47
      years, the following parameters  were analysed: nutritional status (standardized
      body weight and height, serum albumin concentration) and clinical expression of
      disease (lung function - spirometry; biochemical markers of liver function - ALT,
      AST, GGT; respiratory tract colonization by Pseudomonas aeruginosa; diabetes;
      cirrhosis, non-cirrhotic liver disease; exocrine pancreatic function - fecal
      elastase-1 concentration; blood clotting -  INR  and  vitamin  A
      supplementation). RESULTS: Median vitamin A concentration in the study group was
      383.0 ng/ml (1st-3rd quartile: 316.5-457.0). Vitamin A deficiency was found in 32
      (16.3%) subjects studied. Vitamin A concentrations above the reference range were
      observed only in 3 (1.5%) CF patients. CF patients with vitamin A deficiency were
      significantly older and had lower values of FEV1 compared to CF subjects with
      normal vitamin A status. Moreover, vitamin A deficiency occurred more frequently
      in CF patients with diabetes, Pseudomonas aeruginosa colo- nization, worse lung
      function and in those without vitamin A supplementation. However, in multiple
      linear regression analyses, none of the independent variables was documented to
      be important for predicting vita- min A status. CONCLUSIONS: Vitamin A body
      resources in CF patients are mostly normal. Moreover, there are no good de-
      terminants of vitamin A status in these patients. Further studies targeted at
      exploring potential toxicity and deficiencies of vitamin A in CF patients are
      needed.

PMID- 29055983
TI  - [Strengthening the clinical research in long-term therapy of hepatitis B:
      beginning with the end in mind].
AB  - Chronic hepatitis B is a serious public health issue in China. The clinical
      management of hepatitis B is effective with the emergence of antiviral agents.
      The outcome of long-term therapy and nucleos(t)ide analogues stopping rules are
      currently unresolved issues and unmet needs. Thus, we need to pay more attention
      to clinical research to build large-sample and long-term follow-up cohorts and
      begin with the end in mind. We believe that the way to resolve the issues above
      will be found with the efforts of generations.

PMID- 29055984
TI  - [Effect of clinical first-line Antiviral Agents on outcome of chronic hepatitis B
      treatment].
AB  - Chronic hepatitis B is a progressive disease that can develop into cirrhosis,
      liver cancer or even liver failure if it is not treated in time. Antiviral
      therapy is an important means to delay the progression of chronic hepatitis B
      disease, through long-term inhibition of HBV DNA replication can reduce liver
      cell inflammation and necrosis, fibrosis, delaying and reducing liver failure,
      cirrhosis, HCC and other complications, which can improve the life quality and
      prolong survival time. Based on the data of hepatitis B first-line Antiviral
      Agents such as entecavir and tenofovir And so on. being used worldwide, this
      paper expounds the influence of antiviral therapy on the outcome of chronic
      hepatitis B treatment.

PMID- 29055985
TI  - [Off-treatment responses and predictors and after long-term anti-HBV therapy with
      nucleos(t)ide analogues].
AB  - Recurrence rate after cessation of nucleos(t)ide analogues remains high in
      clinical practice. According to current evidences, age, HBsAg level, HB VRNA
      level, time of consolidation therapy and HBV DNA load were considered to be
      associated with off-treatment responses after cessation of nucleos(t)ide
      analogues. Combinative factors of several predictors might perform better in
      future accompanying with further studies of HBV related markers.

PMID- 29055986
TI  - [Host factors influencing the clinical outcome of chronic hepatitis B virus
      infection].
AB  - The clinical outcomes of chronic HBV infection are influenced by the interaction
      between virus, host and environmental factors. Several factors of host include
      age, sex, individual behavior, host genetic polymorphism and intestinal
      microflora, directly or indirectly affect the clinical outcome of chronic HBV
      infection. Therefore, in the management of chronic HBV infection, more attention
      need to be paid not only to antiviral therapy, but also to the impact of host
      factors in order to maximally improve the prognosis of patients.

PMID- 29055987
TI  - [Current status and future views of indicators for clinical outcome of antiviral
      treatment in patients with hepatitis B virus infection].
AB  - The optimal clinical outcomes are the original intention and base to form the
      short-term, long-term and special goals of antiviral treatment in patients with
      hepatitis B virus (HBV) infection. The immediate indicators for assessment of
      antiviral clinical outcomes, which usually need prolonged follow-up, include the
      liver histopathological changes, the occurrence and severity of liver cirrhosis
      and hepatocellular carcinoma (HCC), mortality and survival rates, survival time
      and life quality, prevention rates of Mother-to-Child Transmission and HBV
      reinfection after liver transplantation, etc.

PMID- 29055988
TI  - [Association of HLA-DQ and IFNL4 polymorphisms with hepatitis B virus infection
      and clearance].
AB  - Objective: To confirmed the polymorphisms of HLA-DQ and IFNL4 were associated
      with HBV infection and clearance in a Chinese population. Methods: The Sequenom
      MassARRAY MALDI-TOF system was used to genotype the HLA-DQrs9275319 and
      IFNL4rs368234815, rs12971396, rs12979860, and rs8099917. A binary logistic
      regression test was conducted to estimate the relative risk of these SNPs with
      HBV infection and clearance. Haploview4.2 software and PHASE software (v2.0.2)
      were employed to analyze linkage disequilibrium (LD) and haplotype frequencies.
      The MDR program was applied to analyze interactions between SNP and
      SNP.Statistical analysis was performed using SPSS 19.0 and P-values were
      corrected by Bonferroni's corrections. Results: A total of 1,069 subjects were
      recruited and divided into three groups: 238 healthy controls(HC), 397 with HBV
      related chronic liver disease (CLD), 434 with spontaneous clearance (SC). The
      rs9275319TT was most frequently identified among all groups(86.2% in the CLD
      group, 77.6% in the SC group, and 75.9% in the HC group).Carriage of the
      rs9275319 C allele was a protective factor for chronic HBV infection (the allele
      model: P = 0.000 3, OR,0.514; 95% CI, 0.359-0.738) and clearance (the allele
      model: P = 0.002, OR, 1.659; 95% CI, 1.197-2.300). HLA-DQ rs9275319 showed a
      significant association with HBV infection (allele model, OR, 0.514; 95% CI,
      0.359-0.738, adjusted P = 0.000 3) and spontaneous clearance (allele model, OR,
      1.659; 95% CI, 1.197-2.300, adjusted P = 0.002). However, there was no
      association between IFNL4 polymorphism and HBV infection((allele model: P = 0.082
      for rs368234815; P = 0.063 for rs12971396; P = 0.517 for rs12979860; P =0.695 for
      rs8099917) or spontaneous clearance ((allele model: P = 0.358 for rs368234815; P
      = 0.105 for rs12971396; P = 0.640 for rs12979860; P = 0.640 for rs8099917;all P >
      0.05). The multifactor dimensionality reduction (MDR) test showed there was a
      three-way interaction (rs12971396, rs12979860, and rs9275319) between IFNL4 and
      HLA-DQ polymorphisms for HBV infection (permutation P = 0.009 for the best factor
      model) and clearance (permutation P = 0.014 for the best factor model).
      Conclusion: The SNP-SNP interaction between HLA-DQ and IFNL4 is associated with
      the regulation of HBV infection and natural clearance.

PMID- 29055989
TI  - [The Value of SMI in the Evaluation of interventional therapy of liver cancer].
AB  - Objective: To evaluate the value of super microvascular imaging(SMI) for
      evaluating the effect of interventional therapy of liver cancer. Methods: A total
      of 30 patients with 40 leisions were enrolled in this study, from the tumor
      intervention department in the third affiliated hospital of suzhou
      university.This patients were underwent TACE, after the treatment 1 month, CDFI,
      SMI, and CT were study respectively. Using the continuity correction McNemar
      matching chi-square test, with P < 0.05 for the standard , CDFI and SMI shows the
      difference in monitoring the microvascular imaging in and around the tumors
      leisions. Results: A total of 30 patients, 12 cases were primary liver cancer (7
      cases combined with liver cirrhosis), 18cases were metastatic liver cancer; 30
      cases including 25 single and 5 multiple. Significant difference were found
      between CT and SMI in detecting blood flows inside the lesion (chi2 = 8.642 9, P
      < 0.05), and were also found between CT and CDFI in detecting blood flows inside
      the lesion (chi2 = 16.961 5, P < 0.05). The AUROC, sensitivity, specificity,
      accuracy, PPV and NPV of CDFI were 0.647, 29.4%,100%,29.4%,100%,20.0%, while in
      SMI were 0.809, 61.8%,100%,61.7%,100%,31.5%, respectively. Conclusions: SMI SMI
      can detect the microvascular inside the lesions. This new method was superior to
      CDFI, achieving the same effect as CT.

PMID- 29055990
TI  - [Neovascularization aggravated hepatic fibrosis in combined hypoxia NASH rat
      model].
AB  - Objective: To optimize the construction of combined hypoxia NASH rat model on the
      basis of preliminary work, and to explore the role of neovascularization in the
      process of hepatic fibrosis. Methods: 32 rats were divided randomly to four
      groups that were null control group(A group ), hypoxia group(B group), high fat
      diet group(C group ) and high fat diet plus hypoxia group (D group ),treated with
      null , Intraperitoneal injection of NaNO(2), high fat diet and high fat diet plus
      Intraperitoneal injection of NaNO(2) respectively. Every group was observed for
      16 weeks, B and D group was treated with Intraperitoneal injection of NaNO(2) 20
      mg/kg.d at the laster 8 weeks. Liver histology NASH activity score(NAS) and Fibro
      score(FibroS), biochemical index were detected in this combined hypoxia NASH rat
      model(D group), meanwhile the changes of HIF1alpha, inflammatory factor and
      neovascularization were measured by ELISA, realtime PCR and immunohistochemistry.
      Results: Liver tissue NAS > 4 was seen in C and D group. D group showed NASH
      characteristics, including significantly steatosis at liver acinar 3 area(mostly
      a microvesicular type fat droplets mixed with macrovesicular type), hepatocyte
      balloon degeneration, obvious lobular inflammation, while fibrosis score
      increased significantly, including visible hepatic sinusoid fibrosis, fibrosis
      around portal vein, and bridging fibrosis in a considerable portion of the rats.
      Compared with C group, biochemical indicators of aspartate aminotransferase
      (AST), HIF1alpha, neovascularization-related VEGFA, VEGFR2 mRNA level increased
      obviously and the expression of immunohistochemistry VEGFR2, CD34 enhanced
      markedly in D group(p < 0.05). Conclusion: A combined hypoxia NASH rat model can
      be established throught feeding 16 weeks' high-fat diet then intraperitoneal
      injection of NaNO(2) 20 mg / kg.d at the laster 8 weeks, meanwhile chronic
      hypoxia can accelerate this combined hypoxia NASH model liver fibrosis process.
      In this process neovascularization promoted the formation of hepatic fibrosis in
      this model.

PMID- 29055991
TI  - [Analysis on serological change patterns and clinical epidemiological features].

PMID- 29055992
TI  - [Analysis of pathological changes and related factors of liver tissue in patients
      with low level HBsAg].

PMID- 29055993
TI  - [Association of interleukin-28B and interferon-lambda 4 gene polymorphisms with
      response to pegylated interferon plus ribavirin antiviral treatment for chronic
      hepatitis C patients].

PMID- 29055994
TI  - [The value of serum prealbumin combined with MELD score in predicting the
      prognosis of patients with decompensated cirrhosis].

PMID- 29055995
TI  - [Study on the phenotype changes of Kupffer cells in non-alcoholic fatty liver].

PMID- 29055996
TI  - [A case of liver cirrhosis complicated by upper gastrointestinal bleeding with
      pyrexia and intrahepatic space-occupying lesion].

PMID- 29055997
TI  - [A case of hereditary hemochromatosis].

PMID- 29055998
TI  - [The importance of hyperdynamic circulation in the progression of liver cirrhosis
      and its therapeutic strategies].
AB  - Portal hypertension is one of the main performance of liver cirrhosis, in
      addition to anatomical factors, hyperdynamic circulatory status caused by
      abnormal splanchnic vascular tension is also very important in this procession.
      We summarised the mechanism and treatment strategies of hyperdynamic circulation
      in cirrhosis, so as to provide some recommendation for clinical practice.

PMID- 29055999
TI  - [The recent research progress in nutritional assessment and intervention
      treatment of liver failure in patients].
AB  - Malnutrition can reduce the body's immune function, and significantly increased
      higher incidence of infection, related complications, leading to higher
      hospitalization days, hospitalization expenses and mortality. At present, the
      nutrition assessment not only has been widely used in tumor disease; kidney
      disease; geriatric disease and other disciplines, but also concentrated in the
      patients with chronic liver disease. However, the clinic application of nutrition
      assessment in liver failure is limited. In the clinical practice work,
      malnutrition commonly comes with the course of patients with liver failure, and
      need to treatment. Therefore, the early judgment on their nutritional status, and
      follow the nutrition characteristics of individualized has gradually become an
      important part of the treatment of liver failure patients.

PMID- 29056000
TI  - [The progress of studying the mechanisms of immune cells in the regulation of non
      alcoholic fatty liver diseases].
AB  - Non-alcoholic fatty liver diseases (NAFLD) are liver diseases which are strongly
      associated with obesity. The incidence of NAFLD has been gradually increased in
      recent years. According to different pathology of the liver, NAFLD include three
      disease states: simple fatty liver, hepatitis (nonalcoholic steatohepatitis,
      NASH) and fatty liver cirrhosis. The accumulations of fat around the internal
      organs, which secrete a wide range of adipokines, such as interleukin-6,
      contribute the development and progress of NAFLD in obesity. In addition, the
      liver has been recognized as an immune organ containing several immune cells, for
      instance, inherited macrophages in the live (kupffer cells), nature killer cells,
      T lymphocytes, T regulatory cells (Tregs), myeloid-derived suppressor cells
      (MDSCs), and dendritic cells. These immune cells secret a number of cytokines,
      such as tumor necrosis factor (TNF-alpha) and monocyte chemoattractant protein
      (MCP-1), play important roles in the development of NAFLD. Moreover, a high level
      of fatty acids in the liver microenvironment, leads to suppress CD4(+)T cells and
      the loss of CD4(+)T cells in the microenvironment of the liver may be one of key
      factors which is associated with the progress of NAFLD to cirrhosis and liver
      cancer. This article aims to review the recent studies in the mechanisms of these
      immune cells involving in the progress of NAFLD, and to explore the novel
      strategies targeting these immune cells to control the prevalence of NAFLD and
      reduce liver fibrosis.

PMID- 29056001
TI  - [Research advances in liver diseases associated with parenteral nutrition].
AB  - For patients with gastrointestinal dysfunction or failure, although parenteral
      nutrition can maintain nutrition and save their lives, lack of food stimulus
      during the fasting period can cause abnormal secretion of gastrointestinal fluid,
      bile, and pancreatic juice, which may result in the abnormal secretion of a
      series of enzymes and lead to the development of various liver diseases. Recent
      research has focused on the prevention and treatment of such diseases, and this
      article reviews the research advances in recent years.

PMID- 29056002
TI  - [Anti-fibrosis of liver, Shouder heavy responsibilities].
AB  - In recent years, many studies have been conducted on liver fibrosis. This article
      introduces the latest advances in the pathogenesis, diagnosis, and treatment of
      liver fibrosis. There is still a long way to go for the research on anti-fibrosis
      therapy, and this difficult problem will finally be solved with the help of
      further studies.

PMID- 29056003
TI  - [New advances in the diagnosis of liver fibrosis].
AB  - Various chronic liver diseases may progress to liver fibrosis or liver cirrhosis.
      Assessment of the degree of liver fibrosis helps with clinical decision-making,
      prognosis prediction, and evaluation of therapeutic effect, and therefore,
      accurate diagnosis and evaluation of the degree of liver fibrosis is a research
      hotspot at present. The advances in the diagnosis of liver fibrosis in recent
      years include the publication of international consensuses and guidelines,
      evaluation of the outcome of liver fibrosis after antiviral therapy, development
      of the diagnosis of liver fibrosis in patients with non-viral hepatitis, and
      constant update of noninvasive diagnostic techniques.

PMID- 29056004
TI  - [Research advances in the treatment of hepatic fibrosis].
AB  - Hepatic fibrosis is a common pathological process in the development of various
      chronic liver diseases into liver cirrhosis. Based on current research findings,
      it is widely believed that the process of hepatic fibrosis is reversible, and
      effective treatment cannot only delay the development of hepatic fibrosis into
      liver cirrhosis, but also alleviate the degree of hepatic fibrosis. Therefore,
      the research on the treatment of hepatic fibrosis is of great clinical
      significance. The article reviews the recent research advances in the treatment
      of hepatic fibrosis.

PMID- 29056005
TI  - [Epigenetics and liver fibrogenesis].
AB  - Epigenetic modification refers to a variety of regulating processes that may
      induce the changes in gene expression without altering DNA sequence. Epigenetic
      mechanisms including DNA methylation, histone modification, and regulatory non
      coding RNAs are involved in hepatic stellate cell activation and liver
      fibrogenesis. A deep understanding of epigenetic mechanisms in liver fibrosis
      helps to identify new markers and therapies for liver fibrosis.

PMID- 29056006
TI  - [Mechanism of Astragaloside prevents cholestatic liver fibrosis through
      inhibition of Notch signaling activation].
AB  - Objective: The Notch signaling pathway is closely related to biliary fibrosis.
      Previous studies have shown that Astragaloside (AS) can prevent the progression
      of cholestatic liver fibrosis. The purpose of this study is to observe the effect
      of AS on the regulation of Notch signaling pathway in biliary fibrosis. Methods:
      Cholestatic liver fibrosis was established by common bile duct ligation (BDL) in
      rats. Two weeks after BDL, the rats were randomly divided into a model group
      (i.e., BDL), an Astragalosides group (AS), and a sorafenib (SORA) positive
      control group and treated for 3 weeks. Bile duct proliferation and liver fibrosis
      were determined by tissue staining. Protein and gene expression were determined
      by immunostaining, immunoblotting and RT-PCR, respectively. Activation of the
      Notch signaling pathway was evaluated by analyzing expressions of Notch-1, -2, 
      3, -4, Jagged (JAG)1, Delta like (DLL)-1, -3, -4, Hes1, Numb and RBP-Jkappa.
      Statistical analysis of variance analysis, q test, P < 0.05 showed that the
      difference was statistically significant. Results: (1) AS significantly reduced
      the deposition of collagen and the Hyp content of liver tissue (500.15 +/- 86.10
      vs. 625.72 +/- 105.62, P = 0.031), and inhibited the activation of hepatic
      stellate cells. (2) AS significantly decreased the protein and mRNA expressions
      of transforming growth factor (TGF)-beta1 (1.02+/-0.15 vs. 1.89+/-0.36, P =
      0.007; 1.17+/-0.18 vs. 1.68+/-0.29, P = 0.013, respectively) and alpha-smooth
      muscle actin (alpha-SMA, 0.41+/-0.11 vs. 0.72+/-0.16, P = 0.003; 1.71+/-0.57 vs.
      2.68+/-0.46, P = 0.008, respectively) compared with BDL group. In contrast, AS
      significantly enhanced expression of the Smad 7 protein compared with the BDL
      group (0.72+/-0.008 vs. 0.33+/-0.001, P = 0.005). AS also reduced biliary
      epithelial cell proliferation. AS reduced the mRNA levels of CK7, CK8 and CK18
      (1.31+/-0.39 vs. 2.63+/-0.82, P = 0.009; 0.71+/-0.09 vs. 0.87+/-0.08, P = 0.031;
      2.56+/-0.32 vs. 3.41+/-0.39, P = 0.010, respectively) and reduced the positive
      areas of CK19 and OV6 (62 337.17+/-21 873.38 vs. 22 5472.67+/-26 933.63, P =
      0.000; 92 237.43+/-15 894.11 vs. 171 298.13+/-61 761.37, P = 0.000,
      respectively). (3) The mRNA expression of Notch-2, -3, -4 and JAG1 were
      significantly reduced in the AS group compared to the BDL group (1.07+/-0.19 vs.
      1.51+/-0.28, P = 0.044; 0.99+/-0.24 vs. 1.18+/-0.10, P = 0.043; 1.36+/-0.42 vs.
      3.40+/-0.44, P = 0.048; 2.62+/-0.43 vs. 3.73+/-0.83, P = 0.046, respectively). In
      contrast, the mRNA level of Numb was clearly enhanced after AS treatment (0.90+/
      0.05 vs. 0.75+/-0.11, P = 0.019). In addition, consistent with the mRNA levels,
      the protein expressions of Notch-2, -3, -4 and JAG1 were reduced significantly
      (1.27+/-0.18 vs. 1.71+/-0.26, P = 0.004; 0.99+/-0.11 vs. 4.38+/-0.60, P = 0.001;
      1.76+/-0.32 vs. 4.01+/-0.74, P = 0.002; 1.62+/-0.33 vs. 2.74+/-0.63, P = 0.002)
      and the Numb protein level was increased significantly (1.50+/-0.15 vs. 0.85+/
      0.11, P = 0.001) in AS group compared with BDL group. Conclusion: AS may prevent
      cholestatic liver fibrosis via inhibition of the Notch signaling pathway, thereby
      inhibiting the abnormal proliferation of biliary epithelial cells. Results
      indicate that AS may be a potential treatment for cholestatic liver disease.

PMID- 29056007
TI  - [Clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive
      chronic hepatitis B patients with suboptimal response to pegylated interferon
      alpha-2a therapy].
AB  - Objective: To investigate the clinical effect of 156-week telbivudine sequential
      therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response
      to pegylated interferon-alpha-2a (Peg-IFN-alpha-2a) therapy. Methods: A total of
      35 HBeAg-positive CHB patients with HBV DNA < 500 IU/ml who were treated with Peg
      IFN-alpha-2a for 48 weeks and did not experience seroconversion of HBeAg were
      given telbivudine sequential therapy for 156 weeks. HBeAg clearance rate, HBeAg
      seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate
      were analyzed. The t-test was used for the analysis of continuous data and the
      chi-square test was used for the analysis of categorical data. A multivariate Cox
      regression analysis was used to identify the influencing factors for HBeAg
      seroconversion. Results: Telbivudine sequential therapy achieved an ideal HBeAg
      seroconversion rate of 87.88% with good tolerability and low drug resistance. The
      HBeAg clearance rate and HBeAg seroconversion rate increased over the time of
      treatment and were 45.45% and 45.45%, respectively, at 24 weeks and 93.94% and
      87.88%, respectively, at 156 weeks. No patient had virologic breakthrough or
      HBsAg clearance during treatment. The multivariate Cox regression analysis showed
      that baseline HBsAg level (hazard ratio [HR] = 0.404, P = 0.003) and > 0.5 lg
      IU/ml reduction in HBeAg at 24 weeks (HR = 2.196, P = 0.048) were predictive
      factors for HBeAg seroconversion at 156 weeks. Conclusions: In HBeAg-positive CHB
      patients with suboptimal response to Peg-IFN-alpha-2a therapy, 156-week
      telbivudine sequential therapy has a good clinical effect and can be used as an
      optimal regimen for such patients.

PMID- 29056009
TI  - [Clinical effect and safety of 144-week treatment with entecavir capsules in
      treatment-naive HBeAg-positive patients with chronic hepatitis B].
AB  - Objective: To investigate the clinical effect and safety of entecavir capsules in
      the treatment of treatment-naive HBeAg-positive patients with chronic hepatitis B
      (CHB). Methods: A total of 158 HBeAg-positive CHB patients were given oral
      entecavir capsules at a dose of 0.5 mg/time once a day for 144 weeks. Clinical
      outcome and safety were evaluated at baseline and at 24, 48, 72, 96, 120, and 144
      weeks of treatment respectively. The Fisher's exact test was used for the
      analysis of categorical data. Results: After 144 weeks of treatment, 90.91% of
      all patients achieved virologic response (< 69 IU/ml), the normalization rate of
      alanine aminotransferase was 88.18%, the clearance rate of HBeAg was 33.33%, and
      the seroconversion rate of HBeAg was 24.07%. Of all patients, 2 dropped out due
      to adverse events and 5 experienced serious adverse reactions. Conclusion:
      Entecavir capsules can inhibit viral replication and have good safety in
      treatment-naive HBeAg-positive CHB patients.

PMID- 29056008
TI  - [Clinical effect and safety of pegylated interferon-alpha-2b injection (Y shape,
      40 kD) in treatment of HBeAg-positive chronic hepatitis B patients].
AB  - Objective: To investigate the clinical effect and safety of long-acting pegylated
      interferon-alpha-2b (Peg-IFN-alpha-2b) (Y shape, 40 kD) injection (180 MUg/week)
      in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with
      standard-dose Peg-IFN-alpha-2a as positive control. Methods: This study was a
      multicenter, randomized, open-label, and positive-controlled phase III clinical
      trial. Eligible HBeAg-positive CHB patients were screened out and randomized to
      Peg-IFN-alpha-2b (Y shape, 40 kD) trial group and Peg-IFN-alpha-2a control group
      at a ratio of 2:1. The course of treatment was 48 weeks and the patients were
      followed up for 24 weeks after drug withdrawal. Plasma samples were collected at
      screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized
      detection. COBAS(r) Ampliprep/COBAS(r) TaqMan(r) HBV Test was used to measure HBV
      DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay
      with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti
      HBe). Adverse events were recorded in detail. The primary outcome measure was
      HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was
      also tested. The difference in HBeAg seroconversion rate after treatment between
      the trial group and the control group and two-sided confidence interval (CI) were
      calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was
      > -10%. The t-test, chi-square test, or rank sum test was used according to the
      types and features of data. Results: A total of 855 HBeAg-positive CHB patients
      were enrolled and 820 of them received treatment (538 in the trial group and 282
      in the control group). The data of the full analysis set showed that HBeAg
      seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the
      control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P =
      0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate
      at week 72 was 30.75% in the trial group and 27.14% in the control group with a
      rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the
      non-inferiority criteria, and the trial group was non-inferior to the control
      group. The two groups had similar incidence rates of adverse events, serious
      adverse events, and common adverse events. Conclusion: In Peg-IFN-alpha regimen
      for HBeAg-positive CHB patients, the new drug Peg-IFN-alpha-2b (Y shape, 40 kD)
      has comparable effect and safety to the control drug Peg-IFN-alpha-2a.

PMID- 29056010
TI  - [Predictive value of single nucleotide polymorphisms of HLA-C and UBE2L3 in
      evaluating the effect of telbivudine antiviral therapy during pregnancy].
AB  - Objective: To investigate the association between single nucleotide polymorphisms
      (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of
      telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through
      a large-sample control study, and to provide a basis for the development of
      individualized blocking strategies for pregnant women with a high viral load.
      Methods: The genotypes of rs3130542 and rs4821116 were determined for 312
      pregnant women with a high viral load who received telbivudine antiviral therapy
      during the second or third trimester of pregnancy, and the dominant model,
      recessive model, and additive model were used to analyze the association between
      the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro
      Wilk test and the Levene test were used to evaluate data normality and
      homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U
      test was selected based on data type and was used for the comparison of means
      between groups. The Hardy-Weinberg equilibrium was used to determine the genotype
      of SNPs, and the dominant model, recessive model, and additive model were used
      for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C
      gene had a significantly higher probability of HBV DNA load >=10(3) IU/ml at the
      time of delivery (P < 0.05) and a significantly higher risk of failure in the
      prevention of mother-to-child transmission, no matter whether they started to
      take telbivudine at week 24 or 28 of pregnancy. The association between the
      genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in
      pregnant women needed to be confirmed by studies with a larger sample size.
      Conclusion: Pregnant women with a high viral load and an AA/AG genotype of
      rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy
      during pregnancy, and early antiviral intervention is recommended for such
      patients.

PMID- 29056011
TI  - [Study on the correlation of the effect of entecavir on Th1/Th2 cytokines level
      in the treatment of chronic hepatitis].
AB  - Objective: To explore the expression level of peripheral blood Th1/Th2 type
      cytokines of chronic hepatitis b (CHB) patients in the entecavir (ETV) antiviral
      treatment, analyze the relationship between various cytokines, and the
      correlation among of cytokines and HBV DNA loads. Methods: Luminex Liquid Chip
      Technology was applied to detect the peripheral blood Th1/Th2 type cytokines
      expression level of CHB patients; At the same time, liver function was detected
      by Fully Automatic Biochemical Analyzer; HBV DNA loads were detected by PCR
      Method; Hepatitis b virology markers were detected by Chemiluminescence Method. F
      test and Pearson correlation analysis were used for statistical analysis.
      Results: Before ETV antiviral treatment, peripheral blood Th1 cytokines IFN gamma
      expression level in patients with CHB increased significantly (P = 0.010)
      compared with the healthy control group while TNF alpha expression level having
      no statistically significant difference (P = 0.095); Th2 type cytokines IL-4, IL
      6, IL-10 levels decreased obviously (P = 0.039, P = 0.014, P = 0.026) compared
      with those in the control group. After 48 weeks of treatment, Th1 cytokines IFN
      gamma and TNF alpha expression levels were reduced significantly (19.2+/-5.03
      pg/ml vs 24.69+/-6.51 pg/ml, and 6.09+/-4.99 pg/ml vs 9.50+/-7.34 pg/ml, P <
      0.001, and P = 0.016) compared with that before treatment; Th2 type cytokines IL
      4, IL-6 expression level increased significantly (33.86+/-22.47 pg/ml vs 21.32+/
      12.84 pg/ml, and 11.65+/-6.91 pg/ml vs 8.51+/-4.94 pg/ml, P = 0.004, and P =
      0.029) compared with that before treatment while IL-10 expression level having no
      statistical significance (P = 0.081). There was disorder and irregularity in the
      correlation between the levels of Th1/Th2 type cytokines. And there was no
      correlation between the various cytokines and HBV DNA loads in patients with CHB.
      Conclusion: ETV can not only inhibit HBV DNA replication, reducing HBV DNA loads,
      but also contribute to regulate Th1/Th2 type cytokines expression level in
      patients with CHB, but there was no correlation between the levels of various
      cytokines, various cytokines and HBV DNA loads.

PMID- 29056012
TI  - [The effect and comparison of commonly used liver-protection drugs for irradiated
      HL-7702 by X].
AB  - Objective: To investigate the effect of different mechanisms of liver-protection
      drugs in clinic and compare which one is best for the proliferation of irradiated
      HL-7702, laying the basis of liver-protection drugs choose in clinic on theory
      and practice. Methods: Human liver parenchyma cells HL-7702 were given single 6
      MV X ray irradiation at a dose of 10Gy, the cells' morphology were detected under
      an inverted microscope at 24h, 48h and 72h. Then, MTT was used to assess the
      survival rate of the cells to evaluate the effect of the X ray. The representive
      medicines which mechanism may relate to RILD were chosen and diluted into various
      concentrations with culture medium according to clinical and relative reports.
      Different concentrations of medicines were used to protect the cells damaged by
      the X ray. Comparing the effect with MTT and measure SOD, MDA for the best one.
      Further research on its protection of oxidative damage. T-test, F test and non-
      paramiter test were used for statistical analysis. Results: 2.5 mg/ml and 1 mg/ml
      of magnesium isoglycyrrhizinate both have an effect on the proliferation of liver
      cells, especially the concentration of 1 mg/ml. The injection of polyene
      phosphatidyl choline show trivial effect at the concentrations of 250 MUmol/L and
      reduced glutathione(GSH) did not demonstrate relative functions. Further research
      on the magnesium isoglycyrrhizinate, found its protection at 48h to oxidative
      damage (P < 0.05), but the effect is weak at 24h and 48h. Conclusions: In three
      kinds of representing medicines, magnesium isoglycyrrhizinate has preferable
      effects on liver parenchyma cells and show a bright future in the treatment of
      RILD.

PMID- 29056013
TI  - [Clinical study of non-alcoholic fatty liver disease and its combined the chronic
      HBV infection].
AB  - Objective: to compared with clinical data between nonalcoholic fatty liver
      disease (NAFLD) and Chronic HBV infection with NAFLD, and to explore the
      relationship between HBV infection and hepatic steatosis. Methods: A total of 81
      patients with clinical data in the Department of Infectious Diseases in Henan
      Provincial People's Hospital from June 2013 to June 2016 were enrolled and
      divided into NAFLD group and HBV combined NAFLD group.Comparison of The levels of
      liver function (ALT, AST, ALP, GGT), blood lipid (TC, TG, HDL, LDL), blood
      glucose (GLU), uric acid (UA), hepatic fibrosis (S) and inflammation (G) And
      hepatic steatosis (F), and to explore the relationship between HBV infection and
      hepatic steatosis. The independent samples t-test or Wilcoxon two -sample test
      was used for comparison of continuous data,and the chi-square test was used for
      comparison of categorical data. Multinomial Logistic regression was used to
      analyze The risk factors of hepatic steatosis, P < 0.05 was considered
      statistically significant. Results: A total of 81 subjects were enrolled, with 31
      in the NAFLD group and 36 in the HBV with NAFLD group. Baseline level comparison:
      ALT (t = -4.379, P < 0.01),AST (t = -3.847, P < 0.01) ,GGT (t = -2.763, P < 0.01)
      and F (chi(2) = 20.341, P < 0.01), There were significant difference (P < 0.05);
      There were no significant differences in the levels of blood lipids, blood
      glucose, uric acid, inflammation and fibrosis. e antigen status of liver
      steatosis is a risk factor, hepatitis B viral load and liver steatosis has
      nothing to do. Conclusion: In addition to HBV infection-related indicators, it is
      difficult to distinguish between NAFLD and NAFLD combined with HBV differences;
      HBV infection and hepatic steatosis have a certain relationship.

PMID- 29056014
TI  - [An analysis of the psychological state of patients with chronic liver diseases].

PMID- 29056015
TI  - [The study of hepatocellular carcinoma molecular typing by high throughput
      sequencing of plasma cell free DNA].

PMID- 29056016
TI  - [The relationship of intestinal endotoxemia and circulating Treg cells in chronic
      hepatitis B patients].

PMID- 29056017
TI  - [Research advances of relationship between non-alcoholic fatty liver disease and
      biliary tract diseases].
AB  - Recent studies have found that non-alcoholic fatty liver disease(NAFLD) has great
      impact on the development of biliary tract diseases. Here in this review, we
      summarized the relationship between NAFLD and the occurrence and development,
      risk factors and severity of cholestasis, gallstones, intrahepatic
      cholangiocarcinoma, primary biliary cirrhosis and bile microbiota, so as to
      further illuminate the pathogenesis of NAFLD and biliary tract diseases, obtain
      better diagnostic and therapeutic outcomes on NAFLD and biliary tract diseases.

PMID- 29056018
TI  - [The role of the balance between Th17 and Treg in liver disease].
AB  - Naive CD4+T cell differentiates into either Th17 or Treg in the microenvironment
      of various cytokines, among that, Th17 is induced by TGF-beta and IL-6, while
      differentiates into Treg when there is only TGF-beta. As the mainly transcription
      factors of Th17 and Treg respectively, RORgammat and Foxp3 have important role in
      maintaining balance of Th17/Treg. Th17 and Treg are function antagonistically, so
      the balance of Th17/Treg means a lot for human body. Liver-a metabolic organof
      the body, it is susceptible to factors in vivo and in vitro. From basal hepatis
      to end-stage malignancy, common liver diseases are mainly including viral
      hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune
      liver disease, hepatocellualr carcinoma and parasitic disease of liver, besides,
      the occurrence and development of all the diseases are correlated to the balance
      of Th17/Treg.

PMID- 29056019
TI  - [Early precise diagnosis and reasonable management of burn wound].
AB  - Early precise diagnosis and reasonable management of burn wound are the
      foundation of burn treatment. They determine not only the outcome of the wound
      but also the prognosis of the burn patient. This article expounds how to diagnose
      the burn wound objectively and precisely at early stage. On the other hand, the
      reasonable management such as cooling therapy, escharectomy or tangential
      excision, and negative pressure wound therapy in the early stage of burn wound is
      mainly discussed.

PMID- 29056020
TI  - [Clinical effect of three dimensional human body scanning system BurnCalc in the
      evaluation of burn wound area].
AB  - Objective: To validate the clinical effect of three dimensional human body
      scanning system BurnCalc developed by our research team in the evaluation of burn
      wound area. Methods: A total of 48 burn patients treated in the outpatient
      department of our unit from January to June 2015, conforming to the study
      criteria, were enrolled in. For the first 12 patients, one wound on the limbs or
      torso was selected from each patient. The stability of the system was tested by 3
      attending physicians using three dimensional human body scanning system BurnCalc
      to measure the area of wounds individually. For the following 36 patients, one
      wound was selected from each patient, including 12 wounds on limbs, front torso,
      and side torso, respectively. The area of wounds was measured by the same
      attending physician using transparency tracing method, National Institutes of
      Health (NIH) Image J method, and three dimensional human body scanning system
      BurnCalc, respectively. The time for getting information of 36 wounds by three
      methods was recorded by stopwatch. The stability among the testers was evaluated
      by the intra-class correlation coefficient (ICC). Data were processed with
      randomized blocks analysis of variance and Bonferroni test. Results: (1) Wound
      area of patients measured by three physicians using three dimensional human body
      scanning system BurnCalc was (122+/-95), (121+/-95), and (123+/-96) cm(2,)
      respectively, and there was no statistically significant difference among them (
      F=1.55, P>0.05). The ICC among 3 physicians was 0.999. (2) The wound area of
      limbs of patients measured by transparency tracing method, NIH Image J method,
      and three dimensional human body scanning system BurnCalc was (84+/-50), (76+/
      46), and (84+/-49) cm(2,) respectively. There was no statistically significant
      difference in the wound area of limbs of patients measured by transparency
      tracing method and three dimensional human body scanning system BurnCalc
      (P>0.05). The wound area of limbs of patients measured by NIH Image J method was
      smaller than that measured by transparency tracing method and three dimensional
      human body scanning system BurnCalc (with P values below 0.05). There was no
      statistically significant difference in the wound area of front torso of patients
      measured by transparency tracing method, NIH Image J method, and three
      dimensional human body scanning system BurnCalc (F=0.33, P>0.05). The wound area
      of side torso of patients measured by transparency tracing method, NIH Image J
      method, and three dimensional human body scanning system BurnCalc was (169+/-88),
      (150+/-80), and (169+/-86) cm(2,) respectively. There was no statistically
      significant difference in the wound area of side torso of patients measured by
      transparency tracing method and three dimensional human body scanning system
      BurnCalc (P>0.05). The wound area of side torso of patients measured by NIH Image
      J method was smaller than that measured by transparency tracing method and three
      dimensional human body scanning system BurnCalc (with P values below 0.05). (3)
      The time for getting information of wounds of patients by transparency tracing
      method, NIH Image J method, and three dimensional human body scanning system
      BurnCalc was (77+/-14), (10+/-3), and (9+/-3) s, respectively. The time for
      getting information of wounds of patients by transparency tracing method was
      longer than that by NIH Image J method and three dimensional human body scanning
      system BurnCalc (with P values below 0.05). The time for getting information of
      wounds of patients by three dimensional human body scanning system BurnCalc was
      close to that by NIH Image J method (P>0.05). Conclusions: The three dimensional
      human body scanning system BurnCalc is stable and can accurately evaluate the
      wound area on limbs and torso of burn patients.

PMID- 29056021
TI  - [Effects of flap or myocutaneous flap combined with fascia lata or composite mesh
      on repairing severe high-voltage electrical burn wounds in abdomen of patients].
AB  - Objective: To investigate the effects of flap or myocutaneous flap combined with
      fascia lata or composite mesh on repairing wounds in abdomen of patients with
      severe high-voltage electrical burn. Methods: From January 2010 to May 2017, 11
      patients with severe high-voltage electrical burn in abdomen were hospitalized in
      our burn wards. In 3 hours to 7 days after burn, operation was performed when
      patients were in stable condition. After debridement, intestines with necrosis or
      perforation in 4 patients with peritoneal defects were resected and intestinal
      anastomosis was performed. The size of abdominal wounds after debridement ranged
      from 13 cm*9 cm to 41 cm*32 cm. Five patients were treated with rectus abdominis
      myocutaneous flap and size of which ranged from 14 cm*10 cm to 30 cm*17 cm. Among
      the above 5 patients, 4 patients with peritoneal defects used composite mesh of
      25 cm*20 cm to enhance abdominal wall. Three patients were treated with tensor
      fascia lata myocutaneous flap, and size of the flap ranged from 24 cm*10 cm to 27
      cm*13 cm. Three patients were treated with anterolateral thigh flap with fascia
      lata, and one of them was treated with the lobulated flap; size of the flap
      ranged from 18 cm*13 cm to 25 cm*15 cm. The later 6 patients used fascia lata of
      flap to enhance abdominal wall. The donor sites were sutured directly or repaired
      with intermediate split-thickness skin graft of thigh. Results: After operation,
      flaps or myocutaneous flaps of patients were survived, and strength of abdominal
      wall recovered. During follow-up of 6 month to 1 year, flaps or myocutaneous
      flaps were in good appearance, with no ankylenteron or abdominal wall hernia.
      Conclusions: Flap or myocutaneous flap combined with fascia lata or composite
      mesh can achieve good effects on repairing severe high-voltage electrical burn
      wounds in abdomen.

PMID- 29056022
TI  - [Clinical effects of middle and low peroneal artery perforator flap with pedicle
      on repairing skin and soft tissue defects of ankle].
AB  - Objective: To investigate clinical effects of middle and low peroneal artery
      perforator flap with pedicle on repairing skin and soft tissue defects of ankle.
      Methods: Twenty patients with skin and soft tissue defects of ankle and exposure
      of tendon and bone were admitted in our burn wards from April 2012 to December
      2015. The size of skin and soft tissue defects ranged from 5 cm*4 cm to 23 cm*10
      cm. Patients were treated with debridement and vacuum sealing drainage (VSD)
      after admission. After VSD treatment for 1 week, flap transplantation operation
      was performed. Middle and low perforating branches of peroneal artery were
      detected by portable Doppler blood flow meter before the operation. Flaps were
      designed and resected according wounds during the operation, with 1 or 2 middle
      and low perforating branches of peroneal artery in flaps. Seventeen patients were
      treated with middle and low peroneal artery perforator flap. Larger wounds with
      exposure of tendon and bone were repaired with middle and low peroneal artery
      perforator flap, and the other wounds were repaired with intermediate split
      thickness skin graft of thigh on the same side in three patients. The size of
      flap ranged from 6 cm*5 cm to 25 cm*12 cm. The donor sites were sutured directly
      or repaired with intermediate split-thickness skin graft of thigh on the same
      side. Results: After operation, 1 patient with partial skin necrosis at the
      distal of the flap because of disorder of venous circulation healed after
      dressing change and physiotherapy, and flaps of the other 19 patients survived
      well. During follow-up of 3 to 36 months, flaps of all patients were in good
      appearance, with no obvious cicatrix, and the affected limbs and ankle joints
      functioned well. Conclusions: Middle and low peroneal artery perforator flap with
      advantages of stable perforating branch, reliable blood supply, and large
      resected size, can repair skin and soft tissue defects of ankle.

PMID- 29056023
TI  - [Effects of improved V-Y advancement flap with major artery perforator on
      repairing skin and soft tissue defects].
AB  - Objective: To explore the effect of improved V-Y advancement flap with major
      artery perforator on repairing several skin and soft tissue defects in whole
      body. Methods: From March 2015 to June 2017, 4 cases with pressure ulcer in
      sacrococcygeal region, 4 cases with pressure ulcer at ischial tuberosity, 2 cases
      with scalp and skull defects at occiput, 1 case with secondary wound after tumor
      resection in axillary region, and 2 cases with skin and soft tissue defects
      caused by other trauma were hospitalized, with disease duration ranging from 1
      week to 6 months. Bones, blood vessels, or nerves were exposed in wounds of 11
      cases. After debridement, wounds with area ranging from 5 cm*4 cm to 15 cm*12 cm
      were repaired by improved V-Y advancement flap with major artery perforator
      including occipital artery perforator, arteria glutaea perforator, intercostal
      artery perforator, and peroneal artery perforator, and the area of flap ranged
      from 11 cm*5 cm to 35 cm*20 cm. Distal end of flaps additionally carried 1 major
      artery perforator in 4 cases. Results: All flaps survived well without
      hemodynamic disorder, and wounds and donor sites healed well. During the follow
      up for 3 to 18 months, the flaps were good in appearance with similar color and
      texture to normal skin around wound and without recurrence of rupture.
      Conclusions: Compared with traditional V-Y advancement flap, the improved V-Y
      advancement flap with major artery perforator has the advantages of larger repair
      area, longer advance distance without tension, simple operation, and good
      appearance after operation, which is beneficial to clinical application.

PMID- 29056024
TI  - [Advances in the research of effects of regulation of cell autophagy on wound
      healing].
AB  - As one of the self-protection mechanism, autophagy widely exists in eukaryotic
      cells. It plays an important role in maintaining cells survival, update, material
      recycling, and tissue homeostasis. A series of researches discovered that
      autophagy played dual function in fibrotic diseases. The induction of autophagy
      can promote the degradation of collagen on one hand, on the other hand, the
      regulation of autophagy through microRNA, transforming growth factor beta, and
      other factors can promote the occurrence of fibrosis. In wound healing, autophagy
      may participate in the pathophysiological processes of inflammation,
      reepithlialization, and wound remodeling. The regulation of cell autophagy may
      become an effective way and the new target for treatment of wound and
      pathological scar.

PMID- 29056025
TI  - [Analysis on on-site rescue and traumatic features of victims involved in gas
      explosion accident in Hangzhou].
AB  - Objective: To investigate the situations of on-site rescue and traumatic features
      of victims involved in gas explosion accident in Hangzhou, so as to provide more
      data support for emergency medical rescues of the similar incidents of massive
      casualty. Methods: Two medical workers with a certain clinical experience were
      sent to Hangzhou 120 emergency medical centers to collect data of the on-site
      rescue on 21st July, 2017, including ambulance call-outs, on-site command and
      traffic conditions, and on-site triage and evacuation of the victims. They were
      then sent to the hospitals receiving the victims to investigate the situations of
      these victims including the general information (such as gender, age, admitted
      hospitals, and number of admission, discharge, and transferring in the first two
      weeks after the accident) and injury assessment [such as injury position and
      type, injury severity evaluation by New Injury Severity Scoring (NISS), and burn
      severity evaluation for victims with burns]. Results: (1) A total of 15
      ambulances reached the accident site for rescue. The traffic and transportation
      were jammed and interrupted after this accident. On-site triage and distribution
      were disorderly conducted. (2) Clinical data of 53 victims were collected,
      including 24 males and 29 females, with the age of 8 to 70 (34+/-14) years old.
      They were sent into 6 hospitals in Hangzhou. Two victims died on the day of
      accident. Up to two weeks after this accident, 28 (52.8%) victims were discharged
      from the hospitals and received follow-up in outpatient department. Five victims
      with severe injuries were transferred to the other hospitals. (3) Based on the
      results of NISS, the injury severities were mild in 29 (54.7%) cases, moderate in
      9 (17.0%) cases, serious in 3 (5.7%) cases, and severe in 12 (22.6%) cases. Those
      2 dead victims were classified into the severe category due to the highest NISS
      score of 75. For all of the victims, skin and soft tissue defects were most
      common. Six (11.3%) victims were combined with burns. According to the
      classification of burn severity, there were one case of mild, one case of
      serious, and 4 cases of severe. Conclusions: The gas explosion accident in
      Hangzhou caused massive casualties with complex injuries. The local emergency
      medical rescue responded quickly, but during the rescue process, lots of aspects
      should be further improved.

PMID- 29056026
TI  - [The expression of SnoN in human hypertrophic scar fibroblasts and the mechanism
      of its participation in hypertrophic scar formation].
AB  - Objective: To investigate the expression of SnoN in human hypertrophic scar
      fibroblasts and the mechanism of its participation in hypertrophic scar
      formation. Methods: Eight patients with hypertrophic scar after burn in need of
      surgery were admitted in our unit from January to October 2013, and then
      hypertrophic scar tissue and normal skin tissue of full-thickness skin donor site
      resected by surgery of the patients were collected. Hypertrophic scar fibroblasts
      and normal skin fibroblasts of patients were isolated with method of explant
      culture and then sub-cultured. Cells of the third to fifth passage were used in
      the following experiments. (1) The protein expressions of SnoN of hypertrophic
      scar fibroblasts and normal skin fibroblasts were assessed with Western blotting.
      (2) The mRNA expressions of SnoN of another batch of hypertrophic scar
      fibroblasts and normal skin fibroblasts were determined with reverse
      transcription polymerase chain reaction. (3) Another batch of hypertrophic scar
      fibroblasts and normal skin fibroblasts were treated with 10 ng/mL transforming
      growth factor beta1 (TGF-beta(1)) for 30 min, 1 h, 2 h, and 6 h, respectively,
      and then the protein expressions and mRNA expressions of SnoN of untreated cells
      and treated cells were detected as above. Data were processed with one way
      analysis of variance and independent sample t test. Results: (1) The protein
      expression of SnoN of hypertrophic scar fibroblasts was 0.020+/-0.003,
      significantly lower than that of normal skin fibroblasts (0.032+/-0.005, t=7.19,
      P<0.05). (2) The mRNA expression of SnoN of hypertrophic scar fibroblasts was
      0.407+/-0.157, with no significant difference from that of normal skin
      fibroblasts (0.339+/-0.095, t=-1.29, P>0.05). (3) The protein expression of SnoN
      of normal skin fibroblasts was increased in a time-dependent fashion with the TGF
      beta(1) stimulation, and the protein expressions of SnoN of cells treated with
      TGF-beta(1) for 30 min, 1 h, 2 h, and 6 h were significantly higher than those of
      untreated cells (with t values from 2.27 to 27.89, P values below 0.05). The
      protein expression of SnoN of hypertrophic scar fibroblasts was decreased in a
      time-dependent fashion with the TGF-beta(1) stimulation, and the protein
      expressions of SnoN of cells treated with TGF-beta(1) for 30 min, 1 h, 2 h, and 6
      h were obviously lower than those of untreated cells (with t values from 10.80 to
      13.85, P values below 0.05). (4) The mRNA expressions of SnoN of normal skin
      fibroblasts and hypertrophic scar fibroblasts were both increased in a time
      dependent fashion with the TGF-beta(1) stimulation, and the mRNA expressions of
      SnoN of the two types of cells treated with TGF-beta(1) for 30 min, 1 h, 2 h, and
      6 h were both significantly higher than those of untreated cells (with t values
      from 18.16 to 58.22, P values below 0.05). Conclusions: The protein expression of
      SnoN in hypertrophic scar fibroblasts is reduced, which weakens its inhibitory
      effect on TGF-beta(1) signal, thus amplifying the TGF-beta(1) signal, and it may
      participate in the formation of hypertrophic scar.

PMID- 29056027
TI  - [Differential expression of microRNAs in serum of severe burn patients and
      analysis of the signaling pathway at early stage].
AB  - Objective: To explore differential expression of microRNAs in serum of patients
      with severe burn and analysis of the signaling pathway at early stage. Methods:
      In this study, we included three healthy adult volunteers and three patients with
      severe burn, conforming to the inclusion criteria and hospitalized in Tongren
      Hospital of Wuhan University & Wuhan Third Hospital in July 2015. Venous whole
      blood of 6 mL of each burn patient and healthy volunteer was collected at 24 to
      48 h post injury of burn patients. The whole blood was divided into burn group
      and healthy control group. Whole blood of 2 mL of each one was used to determine
      white blood cell count and neutrophile granulocyte content. Serum was separated
      from the other whole blood of 4 mL of each one. Half of serum was used to
      determine content of blood glucose, total protein, and albumin; another half of
      serum was used to extract total RNA with Trizol method. The differentially
      expressed microRNA, with differential expression ratio larger than or equal to
      1.500 between 2 groups, were screened by microRNA chip technique. Then cluster
      analysis and functional enrichment analysis of Kyoto encyclopedia of genes and
      genomes (KEGG) signaling pathway were performed on the differentially expressed
      microRNAs. Data were processed with t test. Results: (1) Content of white blood
      cell count, neutrophile granulocyte of whole blood, and blood glucose of serum of
      patients in burn group was obviously higher than that in healthy control group
      (with t values from 4.27 to 7.83, P<0.05 or P<0.01). Content of total protein and
      albumin of serum of patients in burn group was significantly lower than that in
      healthy control group (with t values respectively -12.80 and -12.36, P values
      below 0.01). (2)Compared with those in serum of healthy control group,
      differential expression ratios of 48 microRNAs in serum of burn group were larger
      than 1.500, with 22 up-regulated microRNAs and 26 down-regulated microRNAs.
      MicroRNA expression profile in serum of burn group was different from that of
      healthy control group. (3)Functional enrichment analysis of KEGG signaling
      pathway showed that compared with those in serum of healthy control group,
      microRNAs of differential expression in serum of burn group took part in tumor
      transcription misregulation signaling pathway, tumor proteoglycan signaling
      pathway, long-term potentiation signaling pathway, tumor associated microRNAs
      signaling pathway, citrate cycle signaling pathway, tumor necrosis factor
      signaling pathway, focal adhesion signaling pathway, endocytosis signaling
      pathway, insulin secretion signaling pathway, and estrogen signaling pathway.
      Conclusions: MicroRNA expression profile in serum of patients with severe burn is
      different from that in serum of healthy adults. MicroRNAs of differential
      expression may take part in important pathophysiological process of energy
      metabolism, inflammatory response, and regulation of blood glucose at early stage
      of severe burn.

PMID- 29056028
TI  - [Application advances of three-dimensional bioprinting in burn and plastic
      surgery field].
AB  - Three-dimensional bioprinting is one of the latest and fastest growing
      technologies in the medical field. It has been implemented to print part of the
      transplantable tissues and organs, such as skin, ear, and bone. This paper
      introduces the application status, challenges, and application prospect of three
      dimensional bioprinting in burn and plastic surgery field.

PMID- 29056029
TI  - [Advances in the research of treatment of angiogenesis inhibitor on pathological
      scars].
AB  - Angiogenesis inhibitors are a class of agents that prevent the angiogenesis by
      inhibiting the activation, migration, and proliferation of endothelial cells. In
      recent years, studies have found that there was a close relationship between the
      occurrence of pathological scars and angiogenesis. The vascular density in
      pathological scars is significantly higher than that in normal skin and scars.
      Neovascularization supports the fibroblasts growth and collagen production, which
      contribute to the development of pathological scars. Therefore, the angiogenesis
      inhibitor may become a possible agent for prevention and treatment of
      pathological scars. This review explores the relationship between pathological
      scars and angiogenesis inhibitor.

PMID- 29056030
TI  - Health disparities between lesbian, gay, and bisexual adults and the general
      population in South Korea: Rainbow Connection Project I.
AB  - OBJECTIVES: This study aims to investigate health disparities between lesbian,
      gay, and bisexual (LGB) adults and the general population in Korea, where there
      is low public acceptance of sexual minorities and a lack of research on the
      health of sexual minorities. METHODS: The research team conducted a nationwide
      survey of 2,335 Korean LGB adults in 2016. Using the dataset, we estimated the
      age-standardized prevalence ratios (SPRs) for poor self-rated health,
      musculoskeletal pain, depressive symptoms, suicidal behaviors, smoking, and
      hazardous drinking. We then compared the SPRs of the LGB adults and the general
      population which participated in three different nationally representative
      surveys in Korea. SPRs were estimated for each of the four groups (i.e., gay men,
      bisexual men, lesbians, and bisexual women). RESULTS: Korean LGB adults exhibited
      a statistically significantly higher prevalence of depressive symptoms, suicidal
      ideation and attempts, and musculoskeletal pain than the general population.
      Lesbian and bisexual women had a higher risk of poor self-rated health and
      smoking than the general women population, whereas gay and bisexual men showed no
      differences with the general men population. Higher prevalence of hazardous
      drinking was observed among lesbians, gay men, and bisexual women compared to the
      general population, but was not observed in bisexual men. CONCLUSIONS: The
      findings suggest that LGB adults have poorer health conditions compared to the
      general population in Korea. These results suggest that interventions are needed
      to address the health disparities of Korean LGB adults.

PMID- 29056031
TI  - National human genome projects: an update and an agenda.
AB  - Population genetic and human genetic studies are being accelerated with genome
      technology and data sharing. Accordingly, in the past 10 years, several countries
      have initiated genetic research using genome technology and identified the
      genetic architecture of the ethnic groups living in the corresponding country or
      suggested the genetic foundation of a social phenomenon. Genetic research has
      been conducted from epidemiological studies that previously described the health
      or disease conditions in defined population. This perspective summarizes national
      genome projects conducted in the past 10 years and introduces case studies to
      utilize genomic data in genetic research.

PMID- 29056032
TI  - Decomposing Gender Disparity in Total Physical Activity among Iranian Adults.
AB  - OBJECTIVES: While gender differences in physical activity (PA) have been
      reported, their origin is not well understood. The present study aimed to
      identify factors contributing to this disparity. METHODS: This was a population
      based cross-sectional study based on the 2011 surveillance of risk factors of non
      communicable diseases that was conducted among Iranian adults. Multi-staged
      sampling was performed to obtain the required study sample. The primary outcome
      was gender differences in the prevalence of sufficient physical activity (SPA).
      Total physical activity (TPA) was calculated as metabolic equivalents (MET) per
      minute during a typical week, as recommended by the World Health Organization. On
      this basis, achieving 600 MET-min/wk or more was defined as SPA. The nonlinear
      Blinder-Oaxaca decomposition technique was used to explain the disparity.
      RESULTS: The predicted gap was 19.50%. About one-third of the gap was due to
      differences in the level of observable covariates. Among them, work status
      contributed the most (29.61%). A substantial portion of the gap remained
      unexplained by such differences, of which about 40.41% was related to
      unobservable variables. The differential effects of standard of living,
      ethnicity, and smoking status made the largest contribution, accounting for
      37.36, 35.47, and 28.50%, respectively. CONCLUSIONS: Interventions to reduce the
      gender gap in PA should focus on increasing TPA among housewives and women with
      chronic diseases, as well as those with a higher standard of living. In addition,
      it is essential to explore the impact of ethnicity and smoking status on women's
      TPA in order to promote health.

PMID- 29056033
TI  - A comparison of breast cancer survival among young, middle-aged, and elderly
      patients in southern Iran using Cox and empirical Bayesian additive hazard
      models.
AB  - OBJECTIVES: A survival analysis of breast cancer patients in southern Iran
      according to age has yet to be conducted. This study aimed to quantify the
      factors contributing to a poor prognosis, using Cox and empirical Bayesian
      additive hazard (EBAH) models, among young (20-39 years), middle-aged (40-64
      years), and elderly (>= 65 years) women. METHODS: Data from 1,574 breast cancer
      patients diagnosed from 2002 to 2012 in the cancer registry of Fars Province
      (southern Iran) were stratified into 3 age groups. The Kaplan-Meier method was
      used to estimate the overall survival rates. Cox and EBAH models were applied to
      each age category, and the Akaike information criterion was used to assess the
      goodness-of-fit of the 2 hazard models. RESULTS: As of December 2012, 212 women
      (13.5%) in our study population had died, of whom 43 were young (15.3%), 134
      middle-aged (11.8%), and 35 elderly (22.3%). The 5-year survival probability by
      age category was 0.83 (standard error [SE], 0.03), 0.88 (SE, 0.01), and 0.75 (SE,
      0.04), respectively. CONCLUSIONS: The Nottingham Prognostic Index was the most
      effective prognostic factor. The model based on Bayesian methodology performed
      better with various sample sizes than the Cox model, which is the most widely
      used method of survival analysis.

PMID- 29056034
TI  - Spatial assessment of potential ecological risk of heavy metals in soils from
      informal e-waste recycling in Ghana.
AB  - The rapidly increasing annual global volume of e-waste, and of its inherently
      valuable fraction, has created an opportunity for individuals in Agbogbloshie,
      Accra, Ghana to make a living by using unconventional, uncontrolled, primitive
      and crude procedures to recycle and recover valuable metals from this waste. The
      current form of recycling procedures releases hazardous fractions, such as heavy
      metals, into the soil, posing a significant risk to the environment and human
      health. Using a handheld global positioning system, 132 soil samples based on 100
      m grid intervals were collected and analysed for cadmium (Cd), chromium (Cr),
      copper (Cu), mercury (Hg), lead (Pb) and zinc (Zn). Using geostatistical
      techniques and sediment quality guidelines, this research seeks to assess the
      potential risk these heavy metals posed to the proposed Korle Ecological
      Restoration Zone by informal e-waste processing site in Agbogbloshie, Accra,
      Ghana. Analysis of heavy metals revealed concentrations exceeded the regulatory
      limits of both Dutch and Canadian soil quality and guidance values, and that the
      ecological risk posed by the heavy metals extended beyond the main burning and
      dismantling sites of the informal recyclers to the school, residential,
      recreational, clinic, farm and worship areas. The heavy metals Cr, Cu, Pb and Zn
      had normal distribution, spatial variability, and spatial autocorrelation.
      Further analysis revealed the decreasing order of toxicity, Hg>Cd>Pb> Cu>Zn>Cr,
      of contributing significantly to the potential ecological risk in the study area.

PMID- 29056035
TI  - The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal
      Adenocarcinoma.
AB  - BACKGROUND: Smad4 and PTEN are prognostic indicators for various tumor types.
      Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We
      analyzed and compared the performance of Smad4 and PTEN for predicting the
      prognosis of patients with colorectal adenocarcinoma. METHODS: Combined
      expression patterns based on Smad4+/- and PTEN+/- status were evaluated by
      immunostaining using a tissue microarray of colorectal adenocarcinoma. The
      relationships between the protein expression and clinicopathological variables
      were analyzed. RESULTS: Smad4-/PTEN- status was most frequently observed in
      metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma
      (p<.001). When Smad4-/PTEN- and Smad4+/PTEN+ groups were compared, Smad4-/PTEN-
      status was associated with high N stage (p=.018) and defective mismatch repair
      proteins (p=.006). Significant differences in diseasefree survival and overall
      survival were observed among the three groups (Smad4+/PTEN+, Smad4-/PTEN+ or
      Smad4+/PTEN-, and Smad4-/PTEN-) (all p<.05). CONCLUSIONS: Concurrent loss of
      Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients
      with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

PMID- 29056036
TI  - Extracorporeal membrane oxygenation support in patients with hematologic
      malignancies: to whom and when?

PMID- 29056037
TI  - New insights into the genetics of fibromyalgia.
AB  - Although debate on the concept of fibromyalgia (FM) has been vigorous ever since
      the classification criteria were first published, FM is now better understood and
      has become recognized as a disorder. Recently, FM has come to be considered a
      major health problem, affecting 1% to 5% of the general population. As familial
      aggregations have been observed among some FM patients, genetic research on FM is
      logical. In fact, genome-wide association studies and linkage analysis, and
      studies on candidate genes, have uncovered associations between certain genetic
      factors and FM. Genetic susceptibility is now considered to influence the
      etiology of FM. At the same time, novel genetic techniques, such as microRNA
      analysis, have been used in attempts to improve our understanding of the genetic
      predisposition to FM. In this article, we review recent advances in, and
      continuing challenges to, the identification of genes contributing to the
      development of, and symptom severity in, FM.

PMID- 29056040
TI  - Degradation and Transport of the Chiral Herbicide S-Metolachlor at the Catchment
      Scale: Combining Observation Scales and Analytical Approaches.
AB  - Evaluating pesticide degradation and transport in the soil-surface water
      continuum remains challenging at the catchment scale. Here we investigated the
      dissipation of the chiral herbicide S-metolachlor (SM) in soil in relation to its
      transport in runoff. Analyses of SM, transformation products (TPs, i.e., MESA and
      MOXA), and enantiomers were combined to determine SM degradation at plot and
      catchment scales. Assisted by modeling, we found that the main dissipation
      pathways of SM at the plot scale were degradation (71%), volatilization (5%),
      leaching (8%) and runoff (3%), while 13% of SM persisted in topsoil. This
      highlights the relevance of degradation processes. TPs could trace the different
      discharge contributions: MOXA prevailed in runoff water, whereas MESA was
      associated with slower flowpaths. At the catchment outlet, 11% of SM applied was
      exported in dissolved or particulate phases or as TPs (in SM mass equivalent). A
      single event 1 week after application exported 96% of SM, which underlined the
      potential importance of severe rainfall on seasonal SM export. Enantioselective
      degradation enriched SM in the R-enantiomer over longer periods and may be
      associated with slower flowpaths. Altogether, combining observation scales and
      analytical approaches enabled to quantify SM degradation and to identify how
      degradation controls SM export at the catchment scale.

PMID- 29056038
TI  - Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus
      2017: a position statement of the Korean Diabetes Association.
AB  - In 2017, the Korean Diabetes Association (KDA) published a position statement on
      the use of antihyperglycemic agents for patients with type 2 diabetes mellitus
      (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the
      last update in 2015, many results from clinical trials have been introduced, and
      domestic data from studies performed in Korean patients with T2DM have been
      published. Recently, evidence from large clinical studies assessing
      cardiovascular outcomes following the use of sodium-glucose cotransporter 2
      inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM
      were incorporated into the recommendations. Additionally, new data from clinical
      trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean
      patients with T2DM were added. Following a systematic review and assessment of
      recent evidence, the KDA updated and modified its clinical practice
      recommendations regarding the use of antihyperglycemic agents and revised the
      treatment algorithm for Korean adult patients with T2DM.

PMID- 29056041
TI  - Distribution of Novel and Well-Known Poly- and Perfluoroalkyl Substances (PFASs)
      in Human Serum, Plasma, and Whole Blood.
AB  - Currently, there is limited knowledge on the distribution of poly- and
      perfluoroalkyl substances (PFASs) in different blood matrices, particularly for
      novel PFASs such as polyfluoroalkyl phosphate esters (PAPs) and perfluoroalkyl
      phosphonates (PFPAs). To explore this, serum, plasma, and whole blood from 61
      adults in Oslo, Norway were collected. The largest number of PFASs were detected
      in whole blood. For PAPs and PFPAs, the highest frequencies of detection and
      concentrations were observed in plasma. PAPs contributed to 8% of total PFASs in
      plasma (median, 0.81 ng mL-1). Perfluorohexylphosphonate (PFHxPA) was the
      dominant PFPA, regardless of blood matrix. The relative composition profiles of
      PFASs in blood matrices differed. For some specific PFASs such as
      perfluorooctanesulfonamide (PFOSA) and perfluorohexanoate (PFHxA), the highest
      concentrations were observed in whole blood. The PFAS concentration ratios varied
      between blood matrices, depending on the compounds. However, similar ratios were
      observed for 6:2 polyfluoroalkyl phosphate diester (6:2diPAP) as well as well
      known PFASs such as perfluorooctanesulfonate (PFOS) and perfluorooctanoate
      (PFOA). Besides the determination of 25 PFASs in human blood, this study also
      lead to better understanding of biomonitoring data from different blood matrices,
      which is key knowledge for performing both exposure assessments and
      epidemiological studies.

PMID- 29056039
TI  - Kinetic Insights into Hydrogen Sulfide Delivery from Caged-Carbonyl Sulfide
      Isomeric Donor Platforms.
AB  - Hydrogen sulfide (H2S) is a biologically important small gaseous molecule that
      exhibits promising protective effects against a variety of physiological and
      pathological processes. To investigate the expanding roles of H2S in biology,
      researchers often use H2S donors to mimic enzymatic H2S synthesis or to provide
      increased H2S levels under specific circumstances. Aligned with the need for new
      broad and easily modifiable platforms for H2S donation, we report here the
      preparation and H2S release kinetics from a series of isomeric caged-carbonyl
      sulfide (COS) compounds, including thiocarbamates, thiocarbonates, and
      dithiocarbonates, all of which release COS that is quickly converted to H2S by
      the ubiquitous enzyme carbonic anhydrase. Each donor is designed to release
      COS/H2S after the activation of a trigger by activation by hydrogen peroxide
      (H2O2). In addition to providing a broad palette of new, H2O2-responsive donor
      motifs, we also demonstrate the H2O2 dose-dependent COS/H2S release from each
      donor core, establish that release profiles can be modified by structural
      modifications, and compare COS/H2S release rates and efficiencies from isomeric
      core structures. Supporting our experimental investigations, we also provide
      computational insights into the potential energy surfaces for COS/H2S release
      from each platform. In addition, we also report initial investigations into
      dithiocarbamate cores, which release H2S directly upon H2O2-mediated activation.
      As a whole, the insights on COS/H2S release gained from these investigations
      provide a foundation for the expansion of the emerging area of responsive COS/H2S
      donor systems.

PMID- 29056042
TI  - Promoting Intra- and Intermolecular Interactions in Surface-Enhanced Raman
      Scattering.

PMID- 29056044
TI  - Small-Molecule Fluorescent Probes for Imaging and Detection of Reactive Oxygen,
      Nitrogen, and Sulfur Species in Biological Systems.

PMID- 29056045
TI  - Photocatalytic Generation of Nitrenes for Rapid Diaziridination.
AB  - A blue LED, an organic photocatalyst (rose bengal), and the Lewis acid like
      oxidant PhI(OAc)2 were utilized to generate nitrene intermediates through
      reactions of 1,2-diols and aliphatic amines under mild reaction conditions. A
      versatile and rapid diaziridination strategy was established to construct
      functionalized 1,2-disubstituted diaziridines, diaziridines with chiral
      substituents, and 1,2,3-trisubstituted analogues with excellent reaction rates,
      yields, and stereoselectivities. Control and labeling experiments to elucidate
      the mechanism of this elegant metal-free photocatalyzed cyclization reaction were
      performed.

PMID- 29056043
TI  - Dioxygen Activation and O-O Bond Formation Reactions by Manganese Corroles.
AB  - Activation of dioxygen (O2) in enzymatic and biomimetic reactions has been
      intensively investigated over the past several decades. More recently, O-O bond
      formation, which is the reverse of the O2-activation reaction, has been the focus
      of current research. Herein, we report the O2-activation and O-O bond formation
      reactions by manganese corrole complexes. In the O2-activation reaction, Mn(V)
      oxo and Mn(IV)-peroxo intermediates were formed when Mn(III) corroles were
      exposed to O2 in the presence of base (e.g., OH-) and hydrogen atom (H atom)
      donor (e.g., THF or cyclic olefins); the O2-activation reaction did not occur in
      the absence of base and H atom donor. Moreover, formation of the Mn(V)-oxo and
      Mn(IV)-peroxo species was dependent on the amounts of base present in the
      reaction solution. The role of the base was proposed to lower the oxidation
      potential of the Mn(III) corroles, thereby facilitating the binding of O2 and
      forming a Mn(IV)-superoxo species. The putative Mn(IV)-superoxo species was then
      converted to the corresponding Mn(IV)-hydroperoxo species by abstracting a H atom
      from H atom donor, followed by the O-O bond cleavage of the putative Mn(IV)
      hydroperoxo species to form a Mn(V)-oxo species. We have also shown that addition
      of hydroxide ion to the Mn(V)-oxo species afforded the Mn(IV)-peroxo species via
      O-O bond formation and the resulting Mn(IV)-peroxo species reverted to the Mn(V)
      oxo species upon addition of proton, indicating that the O-O bond formation and
      cleavage reactions between the Mn(V)-oxo and Mn(IV)-peroxo complexes are
      reversible. The present study reports the first example of using the same
      manganese complex in both O2-activation and O-O bond formation reactions.

PMID- 29056046
TI  - Synthesis of All Possible Canonical (3'-5'-Linked) Cyclic Dinucleotides and
      Evaluation of Riboswitch Interactions and Immune-Stimulatory Effects.
AB  - The cyclic dinucleotides (CDNs) c-di-GMP, c-di-AMP, and c-AMP-GMP are widely
      utilized as second messengers in bacteria, where they signal lifestyle changes
      such as motility and biofilm formation, cell wall and membrane homeostasis,
      virulence, and exo-electrogenesis. For all known bacterial CDNs, specific
      riboswitches have been identified that alter gene expression in response to the
      second messengers. In addition, bacterial CDNs trigger potent immune responses,
      making them attractive as adjuvants in immune therapies. Besides the three
      naturally occurring CDNs, seven further CDNs containing canonical 3'-5'-linkages
      are possible by combining the four natural ribonucleotides. Herein, we have
      synthesized all ten possible combinations of 3'-5'-linked CDNs. The binding
      affinity of novel CDNs and GEMM riboswitch variants was assessed utilizing a
      spinach aptamer fluorescence assay and in-line probing assays. The immune
      stimulatory effect of CDNs was evaluated by induction of type I interferons
      (IFNs), and a novel CDN c-AMP-CMP was identified as a new immune-stimulatory
      agent.

PMID- 29056047
TI  - Daily Intake of Chlorogenic Acids from Consumption of Mate (Ilex paraguariensis
      A.St.-Hil.) Traditional Beverages.
AB  - The main objective of this study was to investigate the daily intake of
      chlorogenic acids (CGAs) and methylxanthines by consumers of mate traditional
      beverages (MTBs), terere and chimarrao (Ilex paraguariensis A.St.-Hill). In the
      studied population (450 citizens from Toledo, PR, Brazil), 63% consume the
      chimarrao and 37% terere, with weighted mean daily intakes estimated at 648-2160
      and 244-746 mL, respectively. For every 100 mL of beverage consumed, the average
      amount of total phenol compounds extracted was 673.6 mg for chimarrao and 1184.9
      mg for terere. Regarding CGAs composition, caffeoylquinic acids (CQAs) constitute
      about 38.4% for chimarrao and 55.3% for terere, and dicaffeoylquinic acids
      (diCQAs) represent 61.6 and 44.7% of the extracted compounds, respectively. The
      daily intake of phenolic compounds by MTB consumers was estimated for chimarrao
      (512.5-1708.5 mg/day) and terere (583.0-1779.7 mg/day). These results allow us to
      conclude that MTBs are important dietary sources of CGAs, mainly CQAs and di
      CQAs.

PMID- 29056049
TI  - Formation Kinetics of Mixed Self-Assembled Monolayers of Alkanethiols on
      GaAs(100).
AB  - We report on the formation kinetics of mixed self-assembled monolayers (SAMs)
      comprising 16-mercaptohexadecanoic acid (MHDA) and 11-mercapto-1-undecanol (MUDO)
      thiols on GaAs(100) substrates. These compounds were selected for their potential
      in constructing highly selective and efficient architectures for biosensing
      applications. The molecular composition and quality of one-compound and mixed
      SAMs were determined by the Fourier transform infrared absorption spectroscopy
      measurements. The formation of enhanced-quality mixed SAMs was investigated as a
      function of the molecular composition of the thiol mixture and the proportion of
      ethanol/water solvent used during their arrangement. Furthermore, the formation
      of mixed SAMs has been carried out by successive immersion of MHDA SAMs in MUDO
      thiol solutions and MUDO SAMs in MHDA thiol solution through the process
      involving thiol-thiol substitution. Our results, in addition to confirming that
      water-ethanol-based solvents improve the packing density of single thiol
      monolayers, demonstrate the attractive role of water-ethanol solvents in forming
      superior quality mixed SAMs.

PMID- 29056048
TI  - Metal-Dependent DNA Recognition and Cell Internalization of Designed, Basic
      Peptides.
AB  - A fragment of the DNA basic region (br) of the GCN4 bZIP transcription factor has
      been modified to include two His residues at designed i and i+4 positions of its
      N-terminus. The resulting monomeric peptide (brHis2) does not bind to its
      consensus target DNA site (5'-GTCAT-3'). However, addition of Pd(en)Cl2 (en,
      ethylenediamine) promotes a high-affinity interaction with exquisite selectivity
      for this sequence. The peptide-DNA complex is disassembled by addition of a
      slight excess of a palladium chelator, and the interaction can be reversibly
      switched multiple times by playing with controlled amounts of either the metal
      complex or the chelator. Importantly, while the peptide brHis2 fails to
      translocate across cell membranes on its own, addition of the palladium reagent
      induces an efficient cell internalization of this peptide. In short, we report
      (1) a designed, short peptide that displays highly selective, major groove DNA
      binding, (2) a reversible, metal-dependent DNA interaction, and (3) a metal
      promoted cell internalization of this basic peptide.

PMID- 29056051
TI  - Reductive Alkylation of Tertiary Lactams via Addition of Organocopper (RCu)
      Reagents to Thioiminium Ions.
AB  - A simple procedure for the conversion of tertiary lactams to 2-monoalkylated
      cyclic amines is described. The reaction sequence involves conversion of a lactam
      to a thioiminium ion followed by reaction with an organocopper (RCu) reagent and
      final reduction with triacetoxyborohydride. The reaction is high yielding and
      shows an excellent functional group tolerance. Its utility is demonstrated by a
      rapid synthesis of indolizidine 167B. The excellent chemoselectivity of the
      process, where only monoalkylation products are formed, is rationalized by a
      mechanism involving the formation of a transient enamine.

PMID- 29056050
TI  - The Impact of Parbaking on the Crumb Firming Mechanism of Fully Baked Tin Wheat
      Bread.
AB  - The impact of parbaking on the quality and shelf life of large tin bread baked
      from 270 g of wheat flour was investigated using a proton nuclear magnetic
      resonance method combined with techniques that measure at different length
      scales. With increasing partial baking time, the resilience of fresh partially
      baked crumb increased because of its more extended amylose and gluten networks.
      During subsequent storage, the crumb became more firm due to an increased extent
      of amylopectin retrogradation and moisture redistribution. Although only
      amylopectin retrogradation was reversed during final baking, a fresh fully baked
      (FB) bread with reversed crumb softness was obtained. Furthermore, the rate of
      crumb firming during final storage of FB bread was not higher than that of
      conventionally baked bread. This was attributed to the high crumb to crust ratio
      of large tin bread which caused the crumb moisture content to remain sufficiently
      high despite nonreversible moisture redistribution during intermediate storage.

PMID- 29056052
TI  - [Articles of the Hungarian Medical Journal from April, 1999].

PMID- 29056054
TI  - [Articles of the Hungarian Medical Journal from April, 2000].

PMID- 29056053
TI  - [Articles of the Hungarian Medical Journal from October, 1999].

PMID- 29056055
TI  - [Articles of the Hungarian Medical Journal from September, 1999].

PMID- 29056056
TI  - [Articles of the Hungarian Medical Journal from February, 1999].

PMID- 29056057
TI  - [Articles of the Hungarian Medical Journal from August, 1999].

PMID- 29056058
TI  - Novel strategy using tryptic peptide immunoaffinity-based LC-MS/MS to quantify
      denosumab in monkey serum.
AB  - AIM: Denosumab is a recombinant fully human IgG2 that has a high affinity and
      specificity for human RANKL. Commercially available RANKL labeled with an Fc
      fragment cannot be used to establish an indirect ELISA. To characterize denosumab
      pharmacokinetic a robust and accuracy method should be developed urgently.
      RESULTS: In this study, an immunoaffinity enrichment method coupled with LC-MS/MS
      was established. The LC-MS/MS method acquired a linear range from 0.1 to 30
      MUg/ml. The intra- and inter-run precision (CV%) was within 11.5 and 10.5%,
      respectively. More importantly, the LC-MS/MS pharmacokinetic data were consistent
      with ELISA. CONCLUSION: This approach accelerated the quantification, reduced the
      costs and provided an alternative in case of lacking the special antigen to
      denosumab or a RANKL-biotinylated reagent.

PMID- 29056059
TI  - Addressing the challenges of biomarker calibration standards in ligand-binding
      assays: a European Bioanalysis Forum perspective.
AB  - The analysis of biomarkers by ligand-binding assays offers significant challenges
      compared with the bioanalysis of small and large molecule drugs. The presence of
      endogenous analyte is a commonly cited issue. Also the sourcing and application
      of appropriate calibration or reference standards can present many issues. One of
      the main challenges is ensuring the continuity and validity of biomarker data
      when the source or lot number of calibration standard changes within or between
      studies. Several strategies exist in attempting to deal with this and standardize
      the biomarker data through the assay life or looking for ways to compare and
      normalize biomarker data. In this manuscript, the European Bioanalysis Forum view
      on dealing with calibration standards in biomarker assays is described.

PMID- 29056060
TI  - [Articles of the Hungarian Medical Journal from June, 1999].

PMID- 29056061
TI  - [Articles of the Hungarian Medical Journal from May, 1999].

PMID- 29056062
TI  - [Articles of the Hungarian Medical Journal from June, 2000].

PMID- 29056063
TI  - [Articles of the Hungarian Medical Journal from August, 2000].

PMID- 29056064
TI  - Advances in human chorionic gonadotropin detection technologies: a review.
AB  - Human chorionic gonadotropin (HCG) is a glycoprotein secreted by placental
      trophoblast cells in pregnancy. HCG is a heterodimer composed of two different
      alpha- and beta-subunits, with the latter being unique to HCG. As well as being
      the most important diagnostic markers for pregnancy, HCG is also a tumor marker,
      therefore, quantitative detection of HCG is of great value. Numerous advanced
      technologies have been developed for HCG concentration detection including
      electrochemical immunoassay, chemiluminescent immunoassay, fluorescence
      immunoassay, resonance scattering spectrometry, atomic emission spectrometry,
      radioimmunoassay, MS and so on. Some have pursued simple and easy operation,
      while others have emphasized on accuracy and applications in clinical medicine.
      This review provides a comprehensive summary of various methods of detecting HCG.

PMID- 29056065
TI  - Development of sampling method and chromatographic analysis of volatile organic
      compounds emitted from human skin.
AB  - AIM: The studies on volatile organic compounds emitted from skin are an interest
      for chemists, biologists and physicians due to their role in development of
      different scientific areas, including medical diagnostics, forensic medicine and
      the perfume design. This paper presents a proposal of two sampling methods
      applied to skin odor collection: the first one uses a bag of cellulose film, the
      second one, using cellulose sachets filled with active carbon. MATERIALS &
      METHODS: Volatile organic compounds were adsorbed on carbon sorbent, removed via
      thermal desorption and analyzed using gas chromatograph with mass spectrometer.
      RESULTS: The first sampling method allowed identification of more compounds (52)
      comparing to the second one (30). Quantitative analyses for acetone, butanal,
      pentanal and hexanal were done. CONCLUSION: The skin odor sampling method using a
      bag of cellulose film, allowed the identification of many more compounds when
      compared with the method using a sachet filled with active carbon.

PMID- 29056066
TI  - Monoclonal antibodies for chronic pain: a practical review of mechanisms and
      clinical applications.
AB  - Context: Monoclonal antibodies are being investigated for chronic pain to
      overcome the shortcomings of current treatment options. Objective: To provide a
      practical overview of monoclonal antibodies in clinical development for use in
      chronic pain conditions, with a focus on mechanisms of action and relevance to
      specific classes. Methods: Qualitative review using a systematic strategy to
      search for randomized controlled trials, systematic and nonsystematic (narrative)
      reviews, observational studies, nonclinical studies, and case reports for
      inclusion. Studies were identified via relevant search terms using an electronic
      search of MEDLINE via PubMed (1990 to June 2017) in addition to hand-searching
      reference lists of retrieved systematic and nonsystematic reviews. Results:
      Monoclonal antibodies targeting nerve growth factor, calcitonin gene-related
      peptide pathways, various ion channels, tumor necrosis factor-alpha, and
      epidermal growth factor receptor are in different stages of development.
      Mechanisms of action are dependent on specific signaling pathways, which commonly
      involve those related to peripheral neurogenic inflammation. In clinical studies,
      there has been a mixed response to different monoclonal antibodies in several
      chronic pain conditions, including migraine, neuropathic pain conditions (e.g.,
      diabetic peripheral neuropathy), osteoarthritis, chronic back pain, ankylosing
      spondylitis, and cancer. Adverse events observed to date have generally been
      mild, although further studies are needed to ensure safety of monoclonal
      antibodies in early stages of development, especially where there is an overlap
      with non-pain-related pathways. High acquisition cost remains another treatment
      limitation. Conclusion: Monoclonal antibodies for chronic pain have the potential
      to overcome the limitations of current treatment options, but strategies to
      ensure their appropriate use need to be determined.

PMID- 29056069
TI  - Quantifying the Relationship between Capability and Health in Older People: Can't
      Map, Won't Map.
AB  - BACKGROUND: Intuitively, health and capability are distinct but linked concepts.
      This study aimed to quantify the link between a measure of health status (EQ-5D
      3L) and capability (ICECAP-O) using regression-based methods. METHODS: EQ-5D-3L
      and ICECAP-O data were collected from a sample of older people ( n = 584), aged
      over 65 years, requiring a hospital visit and/or care home resident, and
      recruited to one of 3 studies forming the Medical Crisis in Older People (MCOP)
      program in England. The link of EQ-5D-3L with 1) ICECAP-O tariff scores were
      estimated using ordinary least squares (OLS) or censored least absolute deviation
      (CLAD) regression models; and 2) ICECAP-O domain scores was estimated using
      multinomial logistic (MNL) regression. Mean absolute error (MAE), root mean
      squared error (RMSE), absolute difference (AD) between mean observed and
      estimated values, and the R2 statistic were used to judge model performance.
      RESULTS: In this sample of older people ( n = 584), higher scores on the EQ-5D-3L
      were shown to be linked with higher ICECAP-O scores when using linear regression.
      An OLS-regression model was identified to be the best performing model with the
      lowest error statistics (AD = 0.0000; MAE = 0.1208; MSE = 0.1626) and highest
      goodness of fit ( R2 = 0.3532); model performance was poor when predicting the
      lower ICECAP-O tariff scores. The three domains of the EQ-5D-3L showing a
      statistically significant quantifiable link with the ICECAP-O tariff score were
      self-care, usual activities, and anxiety/depression. CONCLUSION: A quantifiable,
      but weak, link between health (EQ-5D-3L) and capability (ICECAP-O) was
      identified. The findings from this study add further support that the ICECAP-O is
      providing complimentary information to the EQ-5D-3L. Mapping between the 2
      measures is not advisable and the measures should not be used as direct
      substitutes to capture the impact of interventions in economic evaluations.

PMID- 29056067
TI  - Usefulness for the combination of G-protein- and beta-arrestin-biased ligands of
      MU-opioid receptors: Prevention of antinociceptive tolerance.
AB  - Background: u-Opioid receptor internalization is considered to be critically
      linked to antinociceptive tolerance. Although u-opioid receptor agonists have
      been administered simultaneously with other drugs to control pain, little
      information is available regarding opioid-opioid interactions. Therefore, the
      present study was designed to further investigate the utility of a new G protein
      biased ligand for u-opioid receptors, TRV130, which has an antinociceptive effect
      without beta-arrestin-dependent u-opioid receptor internalization, and its
      combination with fentanyl using u-opioid receptor-expressing cells and mice.
      Results: In the present study, we confirmed that fentanyl produced a profound
      increase in beta-arrestin-2 recruitment accompanied by u-opioid receptor
      internalization, whereas TRV130 did not induce either the recruitment of beta
      arrestin-2 or u-opioid receptor internalization in u-opioid receptor-expressing
      cells. Under these conditions, beta-arrestin-2 recruitment accompanied by u
      opioid receptor internalization induced by fentanyl was abolished by TRV130,
      whereas TRV130 did not alter the reduction of cyclic adenosine monophosphate
      formation by fentanyl in u-opioid receptor-expressing cells. In a behavioral
      assay, TRV130 exerted an antinociceptive effect in a hot-plate test in mice. In a
      combination test, the antinociceptive effect of TRV130 was synergistically
      increased by fentanyl. Fentanyl induced antihyperalgesia and development of its
      tolerance under a neuropathic pain-like state following sciatic nerve ligation.
      However, treatment of mice with an antinociceptive dose of TRV130 did not induce
      the rapid development of tolerance to its antihyperalgesic effect under a
      neuropathic pain-like state. Furthermore, the rapid development of tolerance to
      the antihyperalgesic effect induced by fentanyl plus TRV130 in mice with sciatic
      nerve ligation was not observed, unlike in the case of fentanyl alone.
      Conclusions: These findings provide evidence that activation of the G protein
      biased pathway through u-opioid receptors can alter signaling in the beta
      arrestin-2 pathway linked to the stimulation of u-opioid receptors. Furthermore,
      the combination of G protein-biased and beta-arrestin-biased ligands of u-opioid
      receptors exerts an ideal antinociceptive effect without the rapid development of
      antinociceptive tolerance.

PMID- 29056068
TI  - DNMT3a contributes to the development and maintenance of bone cancer pain by
      silencing Kv1.2 expression in spinal cord dorsal horn.
AB  - Abstract: Metastatic bone tumor-induced changes in gene transcription and
      translation in pain-related regions of the nervous system may participate in the
      development and maintenance of bone cancer pain. Epigenetic modifications
      including DNA methylation regulate gene transcription. Here, we report that
      intrathecal injection of decitabine, a DNA methyltransferase (DNMT) inhibitor,
      dose dependently attenuated the development and maintenance of bone cancer pain
      induced by injecting prostate cancer cells into the tibia. The level of the de
      novo DNMT3a, but not DNMT3b, time dependently increased in the ipsilateral L4/5
      dorsal horn (not L4/5 dorsal root ganglion) after prostate cancer cells
      injection. Blocking this increase through microinjection of recombinant adeno
      associated virus 5 (AAV5) expressing Dnmt3a shRNA into dorsal horn rescued
      prostate cancer cells-induced downregulation of dorsal horn Kv1.2 expression and
      impaired prostate cancer cells-induced pain hypersensitivity. In turn, mimicking
      this increase through microinjection of AAV5 expressing full-length Dnmt3a into
      dorsal horn reduced dorsal horn Kv1.2 expression and produced pain
      hypersensitivity in the absence of prostate cancer cells injection.
      Administration of neither decitabine nor virus affected locomotor function and
      acute responses to mechanical, thermal, or cold stimuli. Given that Dnmt3a mRNA
      is co-expressed with Kcna2 mRNA (encoding Kv1.2) in individual dorsal horn
      neurons, our findings suggest that increased dorsal horn DNMT3a contributes to
      bone cancer pain through silencing dorsal horn Kv1.2 expression. DNMT3a may
      represent a potential new target for cancer pain management.

PMID- 29056070
TI  - The effects of lead on GABAergic interneurons in rodents.
AB  - Lead is a heavy metal that affects various systems and organs in the body,
      especially the nervous system. In this study, the in vivo and in vitro effects of
      lead on neurons were analyzed. We divided mouse pups into three groups based on
      the concentration of lead exposure: the control group, the low-dose group, and
      the high-dose group. Changes in behavior (measured by an open-field test and a
      tail suspension test), blood lead levels (measured by atomic absorption
      spectrophotometry), the number of GABAergic interneurons (measured by
      immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation
      (measured by pyrosequencing) were determined in the three groups. The lead
      exposed pups showed significantly higher blood lead levels ( p < 0.001). Lead
      exposure caused hyperactivity and reduced the body weight of the exposed mice
      compared with that of the controls. The lead-exposed groups showed significantly
      lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression
      levels of distal-less homeobox ( Dlx) 1, 2, 5, and 6 genes in the cerebral
      cortex. To further clarify the mechanism of Dlx gene downregulation, we selected
      the GE6 cell line, which can differentiate into various subtypes of GABAergic
      interneurons, for in vitro experiments. We found that high levels of lead also
      inhibited the expression of Dlx 1/ 2/ 5/ 6 in vitro, but DNA methylation levels
      were not changed in the GE6 cell line. Furthermore, lead exposure significantly
      decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro.
      The present study revealed that lead exposure can alter behaviors, reduce the
      number of GABAergic interneurons, and change the expression of some important
      genes in neuronal cells.

PMID- 29056071
TI  - Hidradenitis Suppurativa: A Novel Model of Care and an Integrative Strategy to
      Adopt an Orphan Disease.
AB  - Unnecessary investigations, inappropriate treatment, worsening disease, and
      frustration for both patients and health care professionals are the hallmarks of
      hidradenitis suppurativa (HS) management. In light of a new treatment algorithm
      and biologic therapies made available to patients, an HS model of care is
      outlined in this article. The recommendations and management strategy presented
      here have been developed to help address the currently unmet needs of this
      patient population. The patient-centred model of care and disease management
      strategies were developed through the guidance and recommendations of HS medical
      experts in Newfoundland and Labrador. This article lays the foundation for the
      resources and steps required to change the status of this orphan disease and
      firmly embed patients with HS within a coordinated and integrative system of
      care.

PMID- 29056072
TI  - The ShortMAC: Minimum Important Change of a Reduced Version of the Western
      Ontario and McMaster Universities Osteoarthritis Index.
AB  - Study Design Clinical measurement study; secondary analysis of randomized
      clinical trial data. Background A 12-item shortened version (ShortMAC) of the
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a
      condition-specific, patient-reported osteoarthritis index, has been derived,
      published, and validated. The minimum important change (MIC) of the ShortMAC has
      not been reported or compared with the traditional 24-item WOMAC. Objectives To
      investigate the MIC of the 12-item ShortMAC and the traditional 24-item WOMAC
      across 3 levels of patient-perceived global change. Methods The Management of
      OsteoArthritis Trial cohort of 206 consecutive patients with knee or hip
      osteoarthritis was assessed at the initial visit and after 9 weeks of physical
      therapy (n = 155) or usual medical care (n = 51). The global rating of change
      instrument, assessed at the 9-week visit, provided the anchor. The MIC was
      calculated using receiver operating characteristic curve methodology for the
      ShortMAC and the traditional WOMAC, across 3 levels of patient-perceived change
      (small, medium, and large change) defined by the global rating of change. Results
      The MICs for the ShortMAC and traditional WOMAC (both transformed to a scale from
      0 to 100) were 7.9 and 9.8 points for small change, 8.4 and 9.8 points for medium
      change, and 12.1 and 10.1 points for large change, respectively. The MICs of the
      pain and function subscales are also reported for small, medium, and large
      changes. Conclusion The lower point estimates for the MIC of the ShortMAC
      compared with that of the traditional WOMAC, using conventional definitions of
      MIC and half the number of items, indicate greater efficiency for use in clinical
      trials and reduced patient burden. J Orthop Sports Phys Ther 2018;48(2):81-86.
      Epub 21 Oct 2017. doi:10.2519/jospt.2018.7676.

PMID- 29056073
TI  - Bioanalytical methods for the quantification of cis-permethrin and trans
      permethrin in biological samples.

PMID- 29056074
TI  - 2D-LC-MS/MS to measure cleaved high-molecular-weight kininogen in human plasma as
      a biomarker for C1-INH-HAE.
AB  - AIM: C1-INH-HAE is caused by activation of plasma kallikrein which subsequently
      cleaves high-molecular-weight kininogen (HMWK) to generate bradykinin and cHMWK.
      MATERIALS & METHODS: A novel ion-pair 2D LC-MS/MS assay was developed to measure
      the 46 kDa cHMWK in plasma as a biomarker for C1-INH-HAE. The sample preparation
      included sodium dodecyl sulfate denaturation, methanol crash, chymotryptic
      digestion and peptide enrichment by solid phase extraction. RESULTS: The LLOQ was
      200 ng/ml. The overall cHMWK recovery combining crash and digestion was 57.5%.
      The precision of the method was <=12.7% and accuracy <=-13.8%. CONCLUSION: A
      reagent-free LC-MS assay has been developed for the quantitation of 46 kDa cHMWK,
      which was shown to be elevated in plasma of C1-INH-HAE patients due to C1-INH
      deficiency relative to that of healthy subjects.

PMID- 29056075
TI  - An updated review of the JAK1/2 inhibitor (ruxolitinib) in the Philadelphia
      negative myeloproliferative neoplasms.
AB  - Ruxolitinib (Rux), a JAK1/2 inhibitor, has been approved for patients with
      myelofibrosis and in polycythemia vera with inadequate response/intolerance to
      hydroxycarbamide. Studies have demonstrated that Rux improves disease-related
      symptoms and splenomegaly. A late emerging observation from two Phase III trials
      was that Rux was associated with survival advantage in comparison with placebo or
      other available therapies in myelofibrosis. Important data suggest that for
      polycythemia vera Rux improved control of blood counts. Main hematological side
      effects are anemia and thrombocytopenia predominantly at the beginning of the
      treatment. Some studies and case reports highlighted potential risks of
      nonmelanoma skin cancers and increased risk of infection including reactivation
      of hepatitis B, tuberculosis or herpes zoster infections after Rux treatment.

PMID- 29056078
TI  - 18. Unionstagung der Schweizerischen Gesellschaften fur Gefasskrankheiten
      gemeinsam mit der Schweizerischen Gesellschaft fur Ultraschall in der Medizin
      Sektion Gefasse / 18e Congres de l'Union des Societes Suisses des Maladies
      Vasculaires en collaboration avec la Societe Suisse d'Ultrasons en Medecine
      Section Vaisseaux.

PMID- 29056076
TI  - Spotting of external calibration standards on blank dried blood spots as a
      resource-sparing protocol.
AB  - AIM: Dried blood spots (DBS) offer significant ethical and scientific advantages;
      however preparation of calibration curves often times, off-sets some of these
      advantages. We have developed a methodology wherein small volumes of external
      calibration standards can be spiked on to blank DBS cards. RESULTS: A total of 2
      MUl of stock solution spotted on to blank blood spots yielded concentrations that
      were comparable to those obtained using conventional DBS method. The stability of
      six analytes on 10-day-old blank spots was within 80-120%. The new methodology
      was successfully applied to a hydroxycholorquine mouse pharmacokinetics study.
      CONCLUSION: Blank DBS samples can be opportunistically prepared from overweight
      or satellite animals, be stored, and subsequently spiked with standards to
      prepare calibration standards.

PMID- 29056079
TI  - Alcohol consumption and cardiorespiratory fitness in five population-based
      studies.
AB  - Background Poor cardiorespiratory fitness is a risk factor for cardiovascular
      morbidity. Alcohol consumption contributes substantially to the burden of
      disease, but its association with cardiorespiratory fitness is not well
      described. We examined associations between average alcohol consumption, heavy
      episodic drinking and cardiorespiratory fitness. Design The design of this study
      was as a cross-sectional population-based random sample. Methods We analysed data
      from five independent population-based studies (Study of Health in Pomerania
      (2008-2012); German Health Interview and Examination Survey (2008-2011); US
      National Health and Nutrition Examination Survey (NHANES) 1999-2000; NHANES 2001
      2002; NHANES 2003-2004) including 7358 men and women aged 20-85 years, free of
      lung disease or asthma. Cardiorespiratory fitness, quantified by peak oxygen
      uptake, was assessed using exercise testing. Information regarding average
      alcohol consumption (ethanol in grams per day (g/d)) and heavy episodic drinking
      (5+ or 6+ drinks/occasion) was obtained from self-reports. Fractional polynomial
      regression models were used to determine the best-fitting dose-response
      relationship. Results Average alcohol consumption displayed an inverted U-type
      relation with peak oxygen uptake ( p-value<0.0001), after adjustment for age,
      sex, education, smoking and physical activity. Compared to individuals consuming
      10 g/d (moderate consumption), current abstainers and individuals consuming 50
      and 60 g/d had significantly lower peak oxygen uptake values (ml/kg/min) (beta
      coefficients = -1.90, beta = -0.06, beta = -0.31, respectively). Heavy episodic
      drinking was not associated with peak oxygen uptake. Conclusions Across multiple
      adult population-based samples, moderate drinkers displayed better fitness than
      current abstainers and individuals with higher average alcohol consumption.

PMID- 29056080
TI  - Persistency of Biologic Therapies for Plaque Psoriasis in 2 Large Community
      Practices.
AB  - BACKGROUND: Biologics have transformed the management of moderate to severe
      psoriasis. The persistency of biologics lacks real-world data. OBJECTIVES: To
      quantify drug survival of infliximab (IFX), adalimumab (ADA), etanercept (ETA),
      and ustekinumab (UST) and to identify potential factors affecting drug survival.
      METHODS: An observational, retrospective 2-centre study consisting of 906
      patients from private practices in Ontario between July 2003 and June 13, 2016,
      was conducted, including patients with plaque psoriasis receiving commercial
      treatment with ADA, ETA, IFX, and UST. Paper and electronic records of each
      patient were reviewed. RESULTS: Median survival times for UST, IFX, ADA, and ETA
      were respectively, in months, 68, 23, 33, and 28. Female sex was determined to be
      a statistically significant positive predictor of drug survival. Our study was
      consistent with the literature in that UST had the highest survival rate compared
      to the other biologics, and the shape of our drug survival curve suggested that
      loss of drug efficacy is a stochastic occurrence. Compared to other studies, our
      data exhibited lower survival rates at various time points for all the biologics
      studied, and female sex did not predict drug survival in other studies. We also
      investigated potential reasons for differences in biologic survival times between
      different practices; the main differentiator was drug dosage, as higher dosages
      were associated with greater survival. CONCLUSION: UST has a higher drug survival
      rate than ADA, ETA, and IFX, as observed in other studies. When practice patterns
      are compared, dosage difference is the main factor that may cause differing
      survival rates.

PMID- 29056081
TI  - The Risks and Benefits of Cannabis in the Dermatology Clinic.
AB  - Cannabis ( Cannabis sativa/indica), also known as marijuana, has been used for
      medicinal and recreational purposes for millennia. There has been a recent trend
      to legalize the use of cannabis, as illustrated by the recent legalization votes
      in numerous states in the United States and legislation in Canada to allow
      recreational cannabis use. With this increasing consumption of cannabis,
      dermatologists will see increased pressure to prescribe cannabis and will see the
      side effects of cannabis use with greater frequency. There are several approved
      medical indications for cannabis use, including psoriasis, lupus, nail-patella
      syndrome, and severe pain. In addition, very preliminary studies have suggested
      cannabis and its derivatives might have use in acne, dermatitis, pruritus, wound
      healing, and skin cancer. Further well-controlled studies are required to explore
      these potential uses. Conversely, the side effects of cannabis use are relatively
      well documented, and dermatologists should be aware of these presentations. Side
      effects of cannabis use include cannabis allergy manifesting as urticaria and
      pruritus, cannabis arteritis presenting with necrosis and ulcers, and oral
      cancers from cannabis smoke. In this review, we summarize some of the studies and
      reports regarding the medicinal uses of cannabis in the dermatology clinic and
      some of the side effects that might present more often to dermatologists as the
      use of cannabis increases.

PMID- 29056082
TI  - Relationship of Glucose Variability With Glycated Hemoglobin and Daily Mean
      Glucose: A Post Hoc Analysis of Data From 5 Phase 3 Studies.
AB  - BACKGROUND: The association of glucose variability (GV) with other glycemic
      measures is emerging as a topic of interest. The aim of this analysis is to study
      the correlation between GV and measures of glycemic control, such as glycated
      hemoglobin (HbA1c) and daily mean glucose (DMG). METHODS: Data from 5 phase 3
      trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with
      basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes
      (T1D). A generalized boosted model was used post hoc to assess the relationship
      of the following variables with glycemic control parameters (HbA1c and DMG):
      within-day GV, between-day GV (calculated using self-monitored blood glucose and
      fasting blood glucose [FBG]), hypoglycemia rate, and certain baseline
      characteristics. RESULTS: Within-day GV (calculated using standard deviation
      [SD]) was found to have a significant influence on endpoints HbA1c and DMG in all
      3 patient groups. Between-day GV from FBG (calculated using SD), within-day GV
      (calculated using coefficient of variation), and hypoglycemia rate were found to
      significantly influence the endpoint HbA1c in the T2D basal-only group.
      CONCLUSIONS: Lower within-day GV was significantly associated with improvement in
      DMG and HbA1c. This finding suggests that GV could be a marker in the early
      phases of new antihyperglycemic therapy development for predicting clinical
      outcomes in terms of HbA1c and DMG.

PMID- 29056083
TI  - Frontal Fibrosing Alopecia: Update and Review of Challenges and Successes.
AB  - BACKGROUND: Frontal fibrosing alopecia (FFA) is a variant of lichen planopilaris
      (LPP) and is characterised as a progressive cicatricial alopecia affecting the
      frontotemporal hairline. OBJECTIVES: To perform a comprehensive, up-to-date
      review of the etiopathogenesis, clinicopathological features, and therapeutic
      options for FFA. METHODS: A literature search was conducted using PubMed (from
      1946) and Cochrane (from 1991) databases on March 7, 2017. We included all
      retrospective and prospective studies reported in English. Only cases studies
      with reported treatment regimen and outcome were included. No randomised control
      trials were found. MeSH terms used included frontal fibrosing alopecia,
      postmenopausal, histopathologic, cicatricial, and treatment. RESULTS: With an
      increasing incidence of FFA occurring predominantly in postmenopausal women,
      progress has been made clinically and histologically in understanding this
      scarring alopecia. Conflicting results have been reported with various
      treatments, including intralesional or oral corticosteroids, antiandrogens,
      antimalarials, antibiotics, and surgery. To date, no randomised control trials
      for treatment of FFA have been conducted. CONCLUSION: The aetiology and clinical
      course of FFA remain to be established. Unfortunately, despite the numerous
      treatment options available, no one therapeutic regimen has proven effective in
      stopping recession of the hairline and inducing hair growth.

PMID- 29056084
TI  - Acculturation and severity of depression among first-generation Vietnamese
      outpatients in Germany.
AB  - BACKGROUND: Challenges of migration, particularly concerning the process of
      acculturation are associated with an increased risk of mental illness. Vietnamese
      migrants constitute the largest Southeast Asian migrant group in Germany, yet
      there is no data on the relationship between the mental health status and
      acculturation among this population. AIMS: Therefore, the present study examines
      the relationship between two well-established dimensions of acculturation, that
      is, dominant society immersion (DSI) and ethnic society immersion (ESI), the four
      resulting acculturation strategies (integration, assimilation, separation and
      marginalization), and severity of depression. METHODS: A sample of N = 113 first
      generation Vietnamese outpatients from a psychiatric outpatient clinic for
      Vietnamese migrants in Germany was studied regarding their self-reported
      depressive symptoms (Beck Depression Inventory-II (BDI-II)) and acculturation
      (Stephenson Multigroup Acculturation Scale (SMAS)). RESULTS: Consistent with the
      hypotheses, patients reported less severe depressive symptoms, when they reported
      higher orientation toward the German and the Vietnamese society. Moreover, the
      results showed that integrated patients reported a lower severity of depression
      compared to marginalized patients, who reported the highest severity of
      depression. CONCLUSIONS: The findings indicate that among a sample of first
      generation Vietnamese patients with depression, an orientation to both, the
      mainstream society and one's heritage society might serve as a potential
      resource. The rejection of any orientation to any society is associated with an
      increased risk for depression.

PMID- 29056085
TI  - Patient satisfaction with mental health services based on Andersen's Behavioral
      Model.
AB  - OBJECTIVE: The purpose of this article was to assess the satisfaction of adult
      patients who received mental health services (MHS) in healthcare networks staffed
      by multidisciplinary professionals and offering a range of MHS, and to identify
      variables associated with patient satisfaction. METHODS: This cross-sectional
      study included 325 patients with mental disorders (MDs) among 4 Quebec health
      service networks. Data were collected using 9 standardized instruments and
      participant medical records. A 3-factor conceptual framework (predisposing,
      enabling, and needs-related factors) based on Andersen's Behavioral Model was
      used, integrating sociodemographic, clinical, needs-related, service utilization,
      social support, and quality-of-life (QOL) variables. An adjusted multiple linear
      regression model was performed. RESULTS: The global mean score for patient
      satisfaction was 4.11 (minimum: 2.0; maximum: 5.0). Among the enabling factors,
      continuity of care, having a case manager, and help received from services were
      positively associated with patient satisfaction, whereas being hospitalized was
      negatively associated. Among the needs-related factors, the number of needs was
      negatively associated with satisfaction. CONCLUSIONS: Findings demonstrated
      higher levels of satisfaction among patients who received good continuity of care
      and well-managed, frequent services in relation to their needs. Dissatisfaction
      was higher for patients with serious unmet needs or those hospitalized, which
      underlines the importance of taking these particular variables into account in
      the interest of improving MHS delivery and patient recovery.

PMID- 29056087
TI  - Time Trends in Homicide and Mental Illness in Ontario from 1987 to 2012:
      Examining the Effects of Mental Health Service Provision.
AB  - OBJECTIVE: We examine the association between rates of homicide resulting in a
      mental health disposition (termed mentally abnormal homicide [MAH]) and homicides
      without such a disposition, as well as to province-wide psychiatric
      hospitalisation and incarceration rates. METHOD: In this population-based study,
      we investigate all adult homicide perpetrators ( n = 4402) and victims ( n =
      3783) in Ontario from 1987 to 2012. We present annual rates of mentally abnormal
      and non-mentally abnormal homicide and position them against hospitalisation and
      incarceration rates. RESULTS: Among the total sample of homicide accused, 3.7%
      were mentally abnormal. Most (82.5%) had a psychotic disorder at the time of the
      offense. Contrasted with declining hospitalisation, incarceration, and population
      homicide rates, the rate of MAH remained constant at an average of .07
      perpetrators per 100,000 population. The rate of MAH was not associated with
      discharges from or average length of stay in psychiatric hospitals (rho = 0.10;
      0.34, P > 0.10), incarceration rates (rho = 0.16, P = 0.42), or the total
      homicide rate (rho = 0.25, P = 0.22). The proportion of MAH perpetrators with a
      substance use disorder increased modestly over time (beta = 0.35, R2 = 0.12, P =
      0.08). CONCLUSIONS: The rate of MAH has not changed appreciably over the past 25
      years. Declining psychiatric service utilisation was not associated with the rate
      of homicide committed by people with mental illness and, secondarily, was not
      linked to increases in the population homicide or incarceration rates. Substance
      use has become a more prevalent problem for this population.

PMID- 29056086
TI  - Prevalence and Correlates of Autism Spectrum Disorders in Quebec: Prevalence et
      correlats des troubles du spectre de l'autisme au Quebec.
AB  - OBJECTIVE: To estimate the prevalence, comorbidities, and service use of people
      with autism spectrum disorders (ASDs) based on data from Quebec Integrated
      Chronic Diseases Surveillance System (QICDSS). METHODS: We included all residents
      up to age 24 eligible for health plan coverage who were in Quebec for at least 1
      day from January 1, 1996, to March 31, 2015. To be considered as having an ASD,
      an individual had to have had at least 1 physician claim or hospital discharge
      abstract from 2000 to 2015 indicating one of the following ASD diagnosis codes:
      ICD-9 codes 299.0 to 299.9 or their ICD-10 equivalents. RESULTS: The QICDSS shows
      that the prevalence of ASD has risen steadily over the past decade to
      approximately 1.2% ( n = 16,940) of children and youths aged 1 to 17 years in
      2014 to 2015. The same prevalence was obtained using Ministry of Education data.
      Common medical comorbidities included congenital abnormalities of the nervous
      system, particularly in the first year of life. Psychiatric comorbidity was much
      more highly prevalent, especially common mental disorders like anxiety and
      attention-deficit/hyperactivity disorder. Children and youths with ASDs made on
      average 2.3 medical visits per year compared with 0.2 in the general population.
      Between 18 and 24 years old, the mental health needs of individuals with ASDs
      were met less by medical specialists and more by general practitioners.
      CONCLUSION: Information derived from this database could support and monitor
      development of better medical services coordination and shared care to meet the
      continuous and changing needs of patients and families over time.

PMID- 29056088
TI  - Comparison of Vital Statistics Definitions of Suicide against a Coroner Reference
      Standard: A Population-Based Linkage Study.
AB  - OBJECTIVE: We sought to determine the utility of health administrative databases
      for population-based suicide surveillance, as these data are generally more
      accessible and more integrated with other data sources compared to coroners'
      records. METHOD: In this retrospective validation study, we identified all
      coroner-confirmed suicides between 2003 and 2012 in Ontario residents aged 21 and
      over and linked this information to Statistics Canada's vital statistics data
      set. We examined the overlap between the underlying cause of death field and
      secondary causes of death using ICD-9 and ICD-10 codes for deliberate self-harm
      (i.e., suicide) and examined the sociodemographic and clinical characteristics of
      misclassified records. RESULTS: Among 10,153 linked deaths, there was a very high
      degree of overlap between records coded as deliberate self-harm in the vital
      statistics data set and coroner-confirmed suicides using both ICD-9 and ICD-10
      definitions (96.88% and 96.84% sensitivity, respectively). This alignment
      steadily increased throughout the study period (from 95.9% to 98.8%). Other vital
      statistics diagnoses in primary fields included uncategorised signs and symptoms.
      Vital statistics records that were misclassified did not differ from valid
      records in terms of sociodemographic characteristics but were more likely to have
      had an unspecified place of injury on the death certificate ( P < 0.001), more
      likely to have died at a health care facility ( P < 0.001), to have had an
      autopsy ( P = 0.002), and to have been admitted to a psychiatric hospital in the
      year preceding death ( P = 0.03). CONCLUSIONS: A high degree of concordance
      between vital statistics and coroner classification of suicide deaths suggests
      that health administrative data can reliably be used to identify suicide deaths.

PMID- 29056091
TI  - The Case for Nature or Nature-ish.

PMID- 29056090
TI  - Seasonal Differences in Light Exposure and the Associations With Health and Well
      Being in Older Adults: An Exploratory Study.
AB  - OBJECTIVE: This article reports summer verses winter seasonal variations across a
      suite of blue light, illuminance levels and health and well-being indicators.
      BACKGROUND: The quality of lighting in care homes has been assessed previously,
      yet seasonal comparisons and the associations with sleep quality are limited.
      This exploratory study investigates light exposure in two seasons to determine
      the changes over time and the associations with health and well-being. METHODS:
      In a repeated measures design, 16 older people (aged 72-99 years) living in a
      care home had their personal light exposure and sleep/wake patterns monitored for
      4 days. Cognitive ability, mental well-being, daytime physical activity, and
      visual function were assessed. Mean light levels at preset times across the day,
      duration in light exposure over 1,000 lux, and sleep parameters were computed.
      Statistical investigations included correlations exploring associations and
      paired means tests to detect the changes between seasons. RESULTS: The mean
      morning illuminance level in summer was 466 lux and 65 lux in winter. Duration in
      bright light over 1,000 lux was 46 min in summer and 3 min in winter. Light
      measures were significantly higher in summer. There was no statistical difference
      in sleep quality parameters between seasons, but there were significant
      difference in daytime physical activity level (i.e., this was higher in summer).
      CONCLUSION: The findings indicate low level of light exposures experienced in
      both seasons, with exposure levels being particularly low in winter. This
      provides new insights into the limited amount of light older people receive
      independent of season and the possible impacts on sleep and daytime physical
      activity level.

PMID- 29056092
TI  - Meeting Patient Expectations During Hospitalization: A Grounded Theoretical
      Analysis of Patient-Centered Room Elements.
AB  - OBJECTIVES: To identify patient needs and expectations that can be utilized to
      inform the design or renovation of medical-surgical patient rooms in a hospital.
      BACKGROUND: There is an increased interest in supportive room design to increase
      patient satisfaction and improve the healing process. METHODS: Patients' and
      family caregivers' reactions were elicited to intentional room elements embedded
      in a set of five full-scale simulated room prototypes. Small groups of patients
      and caregivers toured two of the five rooms and provided verbal and written
      evaluations of room features. A grounded theory approach was employed to generate
      a codebook, identify the frequency of codes, and to group codes and memos into
      emerging themes. Insights from emergent themes were compared with findings from
      written surveys on the importance of various room design elements completed at
      the beginning of each session. RESULTS: A theoretical design framework was
      generated, showing patients expect a hospital room that provides them with the
      core components of comfort to support healing, facilitates a strong sense of
      connection to people and the outside world, enables quick and independent access
      to the patient's things, and offers suitable levels of control to the patient
      throughout their hospital stay. CONCLUSIONS: The implications for assisting
      architects, healthcare planners, and interior space designers are described using
      this framework, as well as its potential for design guidance. In addition, the
      connection between patient-centered room elements and relevant survey questions
      in publicly reported patient satisfaction scores for hospitals is discussed.

PMID- 29056093
TI  - Designing Safe Patient Rooms.

PMID- 29056094
TI  - Architectural Armor: Preventive Biocidal Surfaces.

PMID- 29056095
TI  - Executive Summary of Key Concepts.

PMID- 29056096
TI  - Spirooxindoles as Potential Pharmacophores.
AB  - OBJECTIVE: The spirooxindole heterocyclic scaffold is found in many natural
      products and has been identified as an important bioactive agent. BACKGROUND:
      Over the past few decades, various spirooxindole-containing compounds have been
      reported to possess biological properties and hence found in the structure of
      many synthetic pharmaceuticals. This mini-review describes the most promising
      examples of this class of compounds possessing biological activity including
      anticancer, anti-inflammatory, and antimicrobial activities. CONCLUSION: The
      current review focuses on the biological activity of compounds containing the
      spirooxindole scaffold.

PMID- 29056097
TI  - Paths to improving care of Australian Aboriginal and Torres Strait Islander women
      following gestational diabetes - CORRIGENDUM.

PMID- 29056098
TI  - The Appraisal of Self-Care Agency Scale - Revised (ASA-R): Adaptation and
      Validation in a Sample of Spanish Older Adults.
AB  - Self-care agency is an important determinant of healthy aging. The Appraisal of
      Self-care Agency Scale (ASA-R) (Sousa et al., 2010) is one of the main instrument
      to assess self-care capacity. The objectives of the study were: 1) to adapt and
      validate ASA-R scale for use in Spanish population; 2) to examine the
      dimensionality, validity and reliability; 3) and to establish the convergent
      validity of ASA-R using a self-reported health measure. The ASA-R Scale and the
      12-item Short Form Health Survey (SF-12) were administered to 488 Spanish seniors
      aged 65 and over. Confirmatory Factor Analysis (CFA) was used to analyze the
      dimensionality, validity and reliability. Convergent validity was tested by
      correlating the ASA-R factors with the SF-12 subscales; correlations were
      significant (p 0.05 (0.436), RMSEA closer to 0 (0.006), SRMR 0.95 (0.996 and
      0.995). The results also demonstrated that ASA-R is a reliable and valid
      instrument. The ASA-R has demonstrated to be a reliable (CR indices > 0.7) and
      valid (AVE > 0.5) instrument in measuring self-care agency among Spanish older
      population.

PMID- 29056099
TI  - Kindness toward One's Self and Body: Exploring Mediational Pathways between Early
      Memories and Disordered Eating.
AB  - Recent literature has emphasized the role played by early emotional experiences
      on body image and eating-related psychopathology. Nevertheless, the mechanisms
      underlying the link between positive rearing experiences and eating
      psychopathology remain scarcely explored. Thus, this study aimed to explore a
      model in which it was hypothesized that early emotional experiences,
      characterized by warmth, safeness, and soothing, are negatively associated with
      disordered eating through higher levels of self-compassion and a more positive
      and caring relationship with one's own body. The study's sample comprised 490
      women who completed an Internet based survey comprising self-report measures of
      interest. Path analysis' results revealed that self-compassion and body
      appreciation fully mediated the impact of early positive emotional memories on
      eating psychopathology, when controlling the effect of age and Body Mass Index.
      The plausibility of the path model was examined by the Chi-Square and the several
      fit indicators which revealed a very good fit, accounting for 49% of eating
      psychopathology's variance. Specifically, results demonstrated that 13% of self
      compassion's variance was explained by positive early emotional memories. Also,
      early positive memories showed both direct and indirect (via self-compassion)
      positive effects on body appreciation, accounting for 34% of its variance.
      Additionally, results revealed that positive early emotional experiences
      predicted lower levels of disordered eating, via higher levels of self-compassion
      and body appreciation. By emphasizing the importance role of self-compassion and
      body appreciation against body image and eating psychopathology, the current
      study may offer important insights for future research and for the development of
      intervention programs.

PMID- 29056100
TI  - International Adoption of Children Surviving the Haitian Earthquake.
AB  - OBJECTIVE: To evaluate resilience and frequency of behavioral symptoms in Haitian
      children internationally adopted before and after the earthquake of January 12,
      2010. METHODS: We conducted a retrospective quantitative study in 40 Haitian
      children. Families were also asked to participate in a qualitative study
      (individual interview at 18-24 months after the earthquake) and to complete State
      Trait Anxiety Inventory (STAI) and STAI for children (STAI-C) questionnaires.
      RESULTS: Demographic and clinical characteristics were similar in the group who
      experienced the earthquake (n=22) and in the group who did not (n=18). The
      families of 30 adoptees were interviewed. There was no statistical difference
      between the two groups for the STAI (P=0.53) and STAI-C (P=0.75) or for the
      frequency of behavioral problems. Plenary adoption was pronounced for 84.6% and
      33.3% of the children adopted in the pre- and post-earthquake group, respectively
      (P=0.02). Children rarely talked about the experience of the earthquake, which,
      by contrast, was a stressful experience for the adoptive families. CONCLUSIONS:
      Haitian children adopted after the earthquake did not express more stress or
      behavioral problems than those adopted before it. However, the possibility of a
      resurgence of mental disorders after age 10 should be borne in mind. (Disaster
      Med Public Health Preparedness. 2018;12:450-454).

PMID- 29056101
TI  - Neuropsychological Assessment at Preschool Age: Adaptation and Validation of the
      McCarthy Scales of Children's Abilities to 4 Year-old Basque-speaking Children.
AB  - Early neuropsychological assessment provides important information for clinical
      practice and research. As previously no tool for neuropsychological assessment
      has been developed in or adapted to Basque, the aim of this study was to adapt
      and validate the McCarthy Scales of Children's Abilities for 4 years old
      children. The adaptation and validation of the original instrument followed the
      methodological steps established by the International Test Commission. We
      examined the psychometric properties of the adapted instrument in 273 Basque
      preschool children (aged between 4 years and 4 months and 4 years and 11 months;
      52.2% boys). Confirmatory factor analysis showed satisfactory fit indexes except
      for the General Cognitive and Memory scales. Most scales presented adequate
      internal consistency (Reliability coefficients ranged between .55 and .81). The
      Basque version also showed evidence of validity based on the relationship between
      neuropsychological development and sex, parental education, attention deficit
      hyperactivity disorder-like behaviours and early neurodevelopment (p < .05;
      effect sizes ranged between Cohen's d = .26 and .52 and r = .15 and 39). The
      Basque MSCA can be regarded as a useful tool to evaluate cognitive and
      psychomotor development in preschool children.

PMID- 29056102
TI  - Flavanone-rich citrus beverages counteract the transient decline in postprandial
      endothelial function in humans: a randomised, controlled, double-masked, cross
      over intervention study - CORRIGENDUM.

PMID- 29056103
TI  - Metabotyping for the development of tailored dietary advice solutions in a
      European population: the Food4Me study.
AB  - Traditionally, personalised nutrition was delivered at an individual level.
      However, the concept of delivering tailored dietary advice at a group level
      through the identification of metabotypes or groups of metabolically similar
      individuals has emerged. Although this approach to personalised nutrition looks
      promising, further work is needed to examine this concept across a wider
      population group. Therefore, the objectives of this study are to: (1) identify
      metabotypes in a European population and (2) develop targeted dietary advice
      solutions for these metabotypes. Using data from the Food4Me study (n 1607), k
      means cluster analysis revealed the presence of three metabolically distinct
      clusters based on twenty-seven metabolic markers including cholesterol,
      individual fatty acids and carotenoids. Cluster 2 was identified as a
      metabolically healthy metabotype as these individuals had the highest Omega-3
      Index (6.56 (sd 1.29) %), carotenoids (2.15 (sd 0.71) um) and lowest total
      saturated fat levels. On the basis of its fatty acid profile, cluster 1 was
      characterised as a metabolically unhealthy cluster. Targeted dietary advice
      solutions were developed per cluster using a decision tree approach. Testing of
      the approach was performed by comparison with the personalised dietary advice,
      delivered by nutritionists to Food4Me study participants (n 180). Excellent
      agreement was observed between the targeted and individualised approaches with an
      average match of 82 % at the level of delivery of the same dietary message.
      Future work should ascertain whether this proposed method could be utilised in a
      healthcare setting, for the rapid and efficient delivery of tailored dietary
      advice solutions.

PMID- 29056104
TI  - A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression
      of insulin signalling and lipid metabolism genes and proteins in male rat
      offspring: effect of folic acid supplementation.
AB  - A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid
      homoeostasis through unknown mechanisms and may be modulated by folic acid. We
      investigated the effect of a maternal HFS diet on glucose homoeostasis,
      expression of genes and proteins associated with insulin signalling and lipid
      metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male
      rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS
      or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma
      insulin and glucose and liver and skeletal muscle gene and protein expression
      were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS
      diet induced higher fasting glucose in offspring v. HFS/F (P=0.027) and down
      regulation (P<0.05) of genes coding for v-Akt murine thymoma viral oncogene
      homolog 2, resistin and v-Raf-1 murine leukaemia viral oncogene homolog 1 (Raf1)
      in offspring skeletal muscle and acetyl-CoA carboxylase (Acaca), fatty acid
      synthase and phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit
      beta in offspring liver. Skeletal muscle neuropeptide Y and hepatic Kruppel-like
      factor 10 were up-regulated in HFS v. CON offspring (P<0.05). Compared with CON,
      Acaca and Raf1 protein expression levels were significantly lower in HFS
      offspring. Maternal HFS induced higher homoeostasis model of assessment index of
      insulin resistance v. CON (P=0.030) and HFS/F was associated with higher insulin
      (P=0.016) and lower glucose (P=0.025). Maternal HFS diet alters offspring insulin
      sensitivity and de novo hepatic lipogenesis via altered gene and protein
      expression, which appears to be potentiated by folate supplementation.

PMID- 29056105
TI  - Colonic and systemic effects of extruded whole-grain sorghum consumption in
      growing Wistar rats.
AB  - Colonic effects of extruded whole-grain sorghum diets were evaluated using a
      model of growing rats. In all, twenty-four male Wistar rats were fed control (C),
      extruded white sorghum (EWS) or red sorghum (ERS). Consumption of sorghum diets
      showed satiety properties, with reduction of caecal pH, and lower activity of
      beta-glucosidase and beta-glucuronidase enzymes. Decreased copper zinc superoxide
      dismutase and manganese superoxide dismutase and increased catalase and
      glutathione peroxidase levels were observed in colonic mucosa. The induction of
      antioxidant enzymes occurred through the activation of the nuclear factor
      erythroid 2-related factor 2 protein and its subsequent translocation into the
      nucleus. ERS was able to decrease the proliferation of proximal mucosa of colon,
      demonstrating a possible effect against colorectal tumourigenesis. EWS increased
      proliferation and also apoptosis, ensuring the re-establishment of homoeostasis
      of the colonic mucosa. No antioxidant systemic effect (serum or hepatic level)
      was observed. It is likely that despite the extrusion the low bioavailability of
      the phenolic compounds of sorghum diets caused them to exert mainly acute effects
      at the colon level. Extruded whole-grain sorghum is a good functional ingredient
      that might be promising in dietary prevention of intestinal diseases.

PMID- 29056107
TI  - Alternative Healthy Eating Index 2010, Dietary inflammatory index and risk of
      mortality: Results from the Whitehall II cohort study and meta-analysis of
      previous DII and mortality studies - CORRIGENDUM.

PMID- 29056106
TI  - The influence of dietary and supplemental calcium on postprandial effects of a
      high-fat meal on lipaemia, glycaemia, C-reactive protein and adiponectin in obese
      women.
AB  - Non-fasting hypertriacylglycerolaemia is a risk factor for CVD and the amount of
      fat in a meal seems to be the main factor influencing postprandial lipaemia.
      Although several studies suggest that Ca can increase faecal fat excretion, it is
      not known whether Ca can decrease postprandial TAG. This study aimed to evaluate
      the influence of dietary Ca (DC) and supplemental Ca (SC) on lipaemia, glucose
      metabolism, C-reactive protein (CRP) and adiponectin during postprandial period
      in obese women challenged with a high-fat meal. In this cross-over controlled
      trial, sixteen obese women aged 20-50 years were randomly assigned to receive
      three test meals (approximately 2900 kJ; 48 % fat): high DC (547 mg DC), high SC
      (HSCM; 500 mg SC-calcium carbonate) and low Ca (42 mg DC). Blood samples were
      collected in the fasting period and at minutes 120 and 240 after meals to
      evaluate total cholesterol and fractions, TAG, glucose, insulin, high-sensitivity
      CRP and adiponectin. Serum levels of TAG and insulin increased significantly
      after all test meals. Only after HSCM total cholesterol did not present a
      significant increase and LDL-cholesterol had a significant decrease. Postprandial
      glucose, HDL-cholesterol, CRP and adiponectin did not present significant changes
      after the three test meals. The comparative analysis of the effects of the three
      test meals on serum lipids, glucose, insulin, CRP and adiponectin revealed no
      significant meal-by-time interaction. These results suggest that in obese women
      challenged with a high-fat meal DC and SC do not interfere with postprandial
      lipaemia, glucose metabolism, CRP and adiponectin.

PMID- 29056108
TI  - A combination of nutrition and genetics is able to reduce age at puberty in
      Nelore heifers to below 18 months.
AB  - Nelore heifers usually begin their reproductive life at ?24 months of age mainly
      due to suboptimal nutritional conditions and genetics. This study aimed to
      determine the effect of expected progeny difference (EPD) for age at first
      calving and average daily gain (ADG) on puberty in Nelore (Bos taurus indicus)
      heifers. A total of 58 weaned heifers (initial BW=174+/-6 kg; age=9+/-1 months)
      were allocated into 28 feedlot pens. Heifers were born from four sires, of which
      two had low EPD for age at first calving (L; n=33) and two had high EPD for age
      at first calving (H; n=25). Then, heifers of each EPD were randomly assigned to
      high ADG (HG; 0.7 kg) or low ADG (LG; 0.3 kg), resulting in four treatments:
      heifers from L sires were submitted to either HG (LHG; n=17) or LG (LLG; n=16),
      and heifers from H sires were submitted to either HG (HHG; n=12), or LG (HLG;
      n=13). The HG heifers were fed a 75% grain diet, whereas the LG heifers received
      93% of forage in their diet. Blood samples were collected at 9, 14, 18, 24 and 28
      months of age for IGF1 and leptin determination. There was a treatment effect
      (P<0.01) on the proportion of heifers that attained puberty by 18 (62%, 0%, 0%
      and 0%), 24 (100%, 6%, 54% and 0%) or 36 (100%, 100%, 100% and 38%) months of age
      for LHG, LLG, HHG and HLG treatments, respectively. In addition, mean age at
      puberty was different across treatments (P<0.01). Heifers from the LHG achieved
      puberty at the earliest age when compared with cohorts from other treatments
      (18.1, 28.9, 23.9 and 34.5 months for LHG, LLG, HHG and HLG, respectively). Serum
      IGF1 concentrations were higher for L heifers compared with H cohorts at 9, 14,
      18, 24 and 28 months of age (P<0.01; treatment*age interaction), whereas
      circulating leptin concentrations were higher (P<0.01; age effect) as heifers
      became older, regardless of the treatments. In conclusion, only Nelore heifers
      with favorable genetic merit for age at first calving were able to attain puberty
      by 18 months of age. In heifers with unfavorable genetic merit for age at first
      calving, supplementary feeding to achieve high ADG was unable to shift the age at
      puberty below 24 months.

PMID- 29056109
TI  - Respiratory Syncytial Virus Infection Control Challenges with a Novel Polymerase
      Chain Reaction Assay in a Tertiary Medical Center.
AB  - OBJECTIVES To evaluate host characteristics, mode of infection acquisition, and
      infection control procedures in patients with a positive respiratory syncytial
      virus (RSV) test result after the introduction of the GenXpert Influenza/RSV
      polymerase chain reaction (PCR) assay. DESIGN Retrospective cohort study.
      PATIENTS Adults with a positive PCR test result for RSV who were hospitalized in
      a tertiary academic medical center between January 2015 and December 2016 were
      included in this study. Our infection control policy applies contact isolation
      precautions only for immunocompromised patients. METHODS Patients were identified
      through 2 databases, 1 consisting of patients isolated because of RSV infection
      and 1 with automatically collected laboratory results. Baseline and clinical
      characteristics were collected through a retrospective medical chart review. The
      rate of and clinical factors associated with healthcare-associated RSV infections
      were evaluated. RESULTS In total, 108 episodes in 106 patients hospitalized with
      a positive Xpert RSV test result were recorded during the study period. Among
      them, 11 episodes were healthcare-associated infections (HAIs) and 97 were
      community-acquired infections (CAIs). The mean length of hospital stay (LOS, 40.2
      vs 11.2 days), the mean number of room switches (3.5 vs 1.7) and ward switches
      (1.5 vs 0.4), and the mean numbers of contact patients (9.9 vs 3.8) were
      significantly longer and higher in the HAI group than in the CAI group (P<.0001).
      Surveillance of microbiology records and clinical data did not reveal evidence
      for a cluster or an epidemic during the 2-year observation period. CONCLUSIONS
      The introduction of a rapid molecular diagnostic test systematically applied to
      patients with influenza-like illness may challenge current infection control
      policies. In our study, patients with HAIs had a prolonged hospital stay and a
      high number of contact patients, and they switched rooms and wards frequently.
      Infect Control Hosp Epidemiol 2017;38:1291-1297.

PMID- 29056110
TI  - Larkinella soli sp. nov., isolated from biological soil crusts.
AB  - A novel bacterial strain, designated MIMbqt9T, was isolated from biological soil
      crusts collected in Erdos Plateau in Inner Mongolia. Cells were light pink, rod
      shaped, aerobic, Gram-reaction-negative, motile by gliding, oxidase- and catalase
      positive. Cell growth could be observed at 5-40  degrees C (optimum at 30 
      degrees C), at pH 4.0-6.0 (optimum at 6.0) and with 1 % (w/v) NaCl. Phylogenetic
      analysis of 16S rRNA gene sequence showed that strain MIMbqt9T was most closely
      related to the members of genus Larkinella, including L. bovis M2T2B15T (92.06
      %), L. arboricola Z0532T (92.00 %) and L. insperata LMG 22510T (91.94 %). The
      major cellular fatty acids of strain MIMbqt9T were C16 : 1omega5c, iso-C15 : 0
      and iso-C17 : 0 3-OH. Polar lipids of the strain MIMbqt9T were mainly composed of
      phosphatidylethanolamine (PE), phosphatidylserine (PS), two unidentified
      aminolipids (AL1 and AL2) and two unidentified phospholipids (PL1 and PL2).
      Menaquinone 7 (MK-7) was the major respiratory quinone. The G+C content of the
      chromosomal DNA was 57.63 mol%. On the basis of morphology, physiology, fatty
      acid composition, phylogeny and 16S rRNA gene sequence analysis, the isolates are
      assigned to a novel species of the genus Larkinella, for which the name
      Larkinella soli sp. nov. is proposed. The type strain is MIMbqt9T (=MCCC
      1K01309T=KCTC 42800T).

PMID- 29056111
TI  - Paenibacillus nebraskensis sp. nov., isolated from the root surface of field
      grown maize.
AB  - A Gram-positive-staining, aerobic, non-endospore-forming bacterial strain (JJ
      59T), isolated from a field-grown maize plant in Dunbar, Nebraska in 2014 was
      studied by a polyphasic approach. Based on 16S rRNA gene sequence similarity
      comparisons, strain JJ-59T was shown to be a member of the genus Paenibacillus,
      most closely related to the type strains of Paenibacillus aceris (98.6 % 16S rRNA
      gene sequence similarity) and Paenibacillus chondroitinus (97.8 %). For all other
      type strains of species of the genus Paenibacillus lower 16S rRNA gene sequence
      similarities were obtained. DNA-DNA hybridization values of strain JJ-59T to the
      type strains of P. aceris and P. chondroitinus were 26 % (reciprocal, 59 %) and
      52 % (reciprocal, 59 %), respectively. Chemotaxonomic characteristics such as the
      presence of meso-diaminopimelic acid in the peptidoglycan, the major quinone MK-7
      and spermidine as the major polyamine were in agreement with the characteristics
      of the genus Paenibacillus. Strain JJ-59T shared with its next related species P.
      aceris the major lipids diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine and an unidentified aminophospholipid, but the
      presence/absence of certain lipids was clearly distinguishable. Major fatty acids
      of strain JJ-59T were anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0, and the
      genomic G+C content is 47.2 mol%. Physiological and biochemical characteristics
      of strain JJ-59T were clearly different from the most closely related species of
      the genus Paenibacillus. Thus, strain JJ-59T represents a novel species of the
      genus Paenibacillus, for which the name Paenibacillus nebraskensis sp. nov. is
      proposed, with JJ-59T (=DSM 103623T=CIP 111179T=LMG 29764T) as the type strain.

PMID- 29056112
TI  - Paenibacillus solanacearum sp. nov., isolated from rhizosphere soil of a tomato
      plant.
AB  - The taxonomic position of a bacterial strain designated T16R-228T, isolated from
      a rhizosphere soil sample of a tomato plant collected from a farm in Buyeo,
      Chungcheongnam-do, Republic of Korea, was determined using a polyphasic approach.
      On the basis of morphological, genetic and chemotaxonomic characteristics, it was
      determined to belong to the genus Paenibacillus. It was an aerobic, Gram-stain
      positive, non-motile, catalase-negative, oxidase-negative rod with peritrichous
      flagella. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol, hydroxyl- phosphatidylethanolamine and one unidentified
      polar lipid. Menaquiones were MK-7. Predominant cellular fatty acids were anteiso
      C15 : 0, C16 : 0 and iso-C16 : 0. DNA G+C content was 56.8 mol%. The phylogenetic
      tree constructed based on the 16S rRNA gene sequences showed the strain formed a
      clade with P. mucilaginosus VKPM B-7519T, P. edaphicus T7T, P. ehimensis KCTC
      3748T, P. koreensis YC300T, P. tianmuensis B27T and P. elgii SD17T, showing the
      highest sequence similarity with P. mucilaginosus VKPM B-7519T (96.5 %). The
      polyphasic data supported that strain T16R-228T was clearly distinguished from
      its closely related species and represents a novel species of the genus
      Paenibacillus for which the name Paenibacillus solanacearum is proposed. The type
      strain is T16R-228T (=KACC 18654T=NBRC 111896T).

PMID- 29056113
TI  - Evaluation of the Thermo Scientific RapidFinderTM Salmonella Species,
      Typhimurium, and Enteritidis Multiplex PCR Kit.
AB  - The Thermo Scientific RapidFinderTM Salmonella Species, Typhimurium, and
      Enteritidis Multiplex PCR Kit (candidate method) is a real-time PCR assay for the
      detection and differentiation of Salmonella spp., and the serovars S.
      Typhimurium, and S. Enteritidis from poultry, pork, and environmental samples.
      The method was validated in comparison to the U.S. Department of Agriculture Food
      Safety and Inspection Service and the U.S. Food and Drug Administration reference
      methods. Thermo Fisher Scientific (Basingstoke, United Kingdom) tested all
      matrixes. In addition, two matrixes were analyzed independently by Q
      Laboratories, Inc. (Cincinnati, OH). Few statistically significant differences
      were found between the candidate and reference methods when analyzed by
      probability of detection. When differences were observed, these were in favor of
      the candidate method. All 200 inclusivity strains and none of the 45 exclusivity
      strains were detected, which demonstrated that the RapidFinder Salmonella
      Species, Typhimurium, and Enteritidis Multiplex PCR Kit was able to detect all
      the major groups of Salmonella, the less common subspecies of S. enterica, and
      the rarely encountered S. bongori. None of the exclusivity isolates analyzed were
      detected. Robustness testing demonstrated that the assay gave reliable
      performance, with specific method deviations outside the recommended parameters.
      Accelerated stability testing was conducted, validating the assay shelf life.

PMID- 29056114
TI  - Nitrincola alkalilacustris sp. nov. and Nitrincola schmidtii sp. nov.,
      alkaliphilic bacteria isolated from soda pans, and emended description of the
      genus Nitrincola.
AB  - Three alkaliphilic and halotolerant bacterial strains, designated ZV-19T, R4-8T
      and S4-12, were isolated from the water of soda pans located in the Kiskunsag
      National Park, Hungary. Cells of all three strains were Gram-staining-negative,
      rod-shaped, motile and non-endospore-forming. They were facultatively anaerobic,
      and oxidase- and catalase-positive. Their major isoprenoid quinone was Q-8, and
      their predominant fatty acids were C18 : 1omega7c, C16 : 1omega7c and C16 : 0.
      The DNA G+C content was 54.5 mol% in strain ZV-19 T and 45.8 mol% in strain R4
      8T. The 16S rRNA gene based phylogenetic analysis showed that all three strains
      were members of the genus Nitrincola (family Oceanospirillaceae, class
      Gammaproteobacteria). Strain ZV-19T showed 96.6 and 95.5 % sequence similarities
      and 19+/-3 and 18+/-3 % DNA-DNA relatedness to Nitrincolalacisaponensis DSM
      16316T and Nitrincolaalkalisediminis JCM 19317T, respectively. Strains R4-8T and
      S4-12 exhibited 97.9 and 98.6 % sequence matches and 34+/-4 and 13+/-8 % DNA-DNA
      hybridization values with N. lacisaponensis DSM 16316T and N. alkalisediminis JCM
      19317T, respectively. According to the phenotypic, chemotaxonomic and
      phylogenetic data, the strains studied represent two novel species, Nitrincola
      alkalilacustris sp. nov. with the type strain ZV-19T (=DSM 29817T=NCAIM B 02612T)
      and Nitrincola schmidtii sp. nov. with the type strain R4-8T (=DSM 100788T=NCAIM
      B.02626T). An emended description of the genus Nitrincola is also presented.

PMID- 29056115
TI  - Nioella aestuarii sp. nov., of the family Rhodobacteraceae, isolated from tidal
      flat.
AB  - A bacterium, designated strain MME-018T, was isolated from a tidal flat of the
      Muui-do in the Republic of Korea and identified within the family
      Rhodobacteraceae. The 16S rRNA gene sequence of the isolate showed the highest
      similarity to that of Nioella sediminis JS7-11T (98.9 %), followed by Nioella
      nitratireducens SSW136T (97.1 %). In phylogenetic analyses, these taxa formed a
      clade at neighbour-joining, maximum-likelihood, and maximum-parsimony algorithms,
      in which it was separated from other genus belonging to the family
      Rhodobacteraceae. Ubiquinone-10 (Q-10) was the major respiratory quinone. Major
      polar lipids included phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylglycerol, two unidentified phospholipids, and an unidentified lipid.
      Major fatty acids were summed feature 8 (C18 : 1omega7c and/or C18 : 1omega6c)
      C16 : 0, cyclo C19 : 0omega8c, and 11-methyl C18 : 1omega7c. Genomic DNA G+C
      content was 61 mol%. Cells were Gram-stain negative, non-motile, aerobic, and rod
      shaped. This strain grew in 1-4 % (w/v) NaCl, at 4-40  degrees C and pH 6.0-8.0,
      with optimal growth in 2 % (w/v) NaCl, at 25-30  degrees C and pH 7.0. DNA-DNA
      hybridization values between strain MME-018T and Nioella sediminis KCTC 42144T
      and Nioella nitratireducens KCTC 32417T were 17+/-3 and 13+/-1 %, respectively.
      On the basis of polyphasic taxonomic analysis, strain MME-018T is proposed to
      represent a novel species of the genus Nioella, for which the name
      Nioellaaestuarii sp. nov. The type strain of Nioellaaestuarii is MME-018T (=KCCM
      43135T=JCM 30752T).

PMID- 29056116
TI  - Sphingobium paulinellae sp. nov. and Sphingobium algicola sp. nov., isolated from
      a freshwater green alga Paulinella chromatophora.
AB  - Two Gram-stain-negative, aerobic, catalase- and oxidase-positive, yellow
      pigmented bacteria, designated strains Pch-BT and Pch-ET, were isolated from a
      green alga Paulinella chromatophora. Both strains were motile short rods with a
      flagellum and optimally grew at pH 6.0-7.0, 25-30  degrees C and 0-1 % NaCl. They
      contained ubiquinone-10 as the major quinone, spermidine as the major polyamine,
      C16 : 0, C14 : 0 2-OH and summed features 3 (comprising C16 : 1omega7c and/or C16
      : 1omega6c) and 8 (comprising C18 : 1omega7c and/or C18 : 1omega6c) as the major
      fatty acids and diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylethanolamine, phosphatidyl-N-methylethanolamine, two
      sphingoglycolipids and phosphatidylcholine as the major polar lipids. DNA G+C
      contents of strains Pch-BT and Pch-ET were 61.4 and 63.9 mol%, respectively.
      Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains Pch
      BT and Pch-ET formed a phylogenic lineage with Sphingobium limneticum 301T.
      Strains Pch-BT and Pch-ET had a 99.86 % 16S rRNA gene sequence similarity and
      their DNA-DNA hybridization (DDH) relatedness value was 40.6 %. Strains Pch-BT
      and Pch-ET were most closely related to S. limneticum 301T with 99.93 and 99.76 %
      16S rRNA gene sequence similarities, respectively and the DDH values between
      strains Pch-BT and Pch-ET and the type strain of S. limneticum were 43.3 and 32.1
      %, respectively. In conclusion, strains Pch-BT and Pch-ET represent novel species
      of the genus Sphingobium, for which the names Sphingobiumpaulinellae sp. nov. and
      Sphingobium algicola sp. nov. are proposed, respectively. The type strains of S.
      paulinellae and S. algicola are Pch-BT (=KACC 19283T=JCM 32054T) and Pch-ET
      (=KACC 19284T=JCM 32055T), respectively.

PMID- 29056117
TI  - Vitamin D Therapy and Relief of Pain.

PMID- 29056118
TI  - Validity of GRACE Risk Score as a Prognostic Marker of In-hospital Mortality
      after Acute Coronary Syndrome.
AB  - OBJECTIVE: To determine validity of GRACE risk score as a determinant of
      immediate death during hospitalization for Acute Coronary Syndrome (ACS) and
      analyze the percentage of cardiac deaths among high, intermediate and low risk
      groups. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY:
      Coronary Care Unit of Mayo Hospital, Lahore, from April to July 2015.
      METHODOLOGY: Patients with acute chest pain were selected according to inclusion
      and exclusion criteria. Online GRACE risk score calculator was used to determine
      the predicted risk of death following ACS according to the score. Data was
      analyzed on SPSS 20. Quantitative data was in the form of median (IQR).
      Discrimination of GRS was evaluated by using c-statistics, area under the ROC
      curve. Calibration of GRS was tested by Hosmer-Lameshow test. The correlation
      between GRACE risk score category and predicted risk of death was determined
      using Kendall's tau-b bivariate correlation test. Shapiro-Wilk test was applied
      to check normality of data. The various parameters of GRACE score were studied in
      patients using Mann-Whitney U-test. The statistically significant p-value was
      <0.05. RESULTS: There were 165 cases in the study. Overall median GRS was 139
      (54). In-hospital deaths were 12.2%. Discrimination of GRS evaluated by area
      under the ROC curve was 0.913 (95% CI 0.843-0.982; p<0.0001). Application of
      Hosmer-Lameshow test revealed a p-value of 0.236. Kendall's tau-b bivariate
      correlation coefficient was 0.384 (p<0.001). CONCLUSION: GRS is an excellent tool
      to stratify patients of ACS into different risk categories according to various
      parameters noted at the time of presentation. The risk of predicted death
      according to the score was variable among different cases, especially those with
      higher scores. Even though GRS is an effective and valid tool, but it has some
      tendency of overestimating probability of death following ACS and may require a
      fine tuning in some cases.

PMID- 29056119
TI  - Polymorphisms in the Growth Differentiation Factor 5 (GDF 5) Gene in Knee
      Osteoarthritis.
AB  - OBJECTIVE: To identify the frequency of the rs143383 SNPin the GDF5 gene, which
      is located in the 5'-untranslated region of Turkish population with knee
      osteoarthritis (OA). STUDY DESIGN: Acase-control study. PLACE AND DURATION OF
      STUDY: Orthopedics and Traumatology Department, Bozok University Medical Faculty,
      Yozgat, Turkey, from 2012 to 2014. METHODOLOGY: Patients diagnosed with OA(n=94)
      and patients who did not have joint complaints (n=279) were enrolled in this
      study. Patients diagnosed with osteoarthritis according to the 1986 American
      College of Rheumatology osteoarthritis criteria and Kellgren and Lawrence scores
      were investigated, based on age, gender, and X-ray findings. Blood samples were
      taken for the identification of GDF5 (rs143383) SNPs by PCR/RFLP, according to a
      standard protocol. RESULTS: This study included 373 patients. The OAgroup (25.2%;
      n=94) was characterized by specific genotypes: TT (39.4%; n=37); heterozygotes
      (TC; 45.7%; n=43); and homozygotes (CC; 14.9%; n=14). The control group (74.8%;
      n=279) was comprised of TT(26.5%; n=74), TC (54.8%; n=153), and CC (18.6%; n=52)
      genotypes. An analysis of rs143383 SNP of the GDF5 gene polymorphism revealed
      that the rs143383 TTgenotype had a higher risk for OA(crude OR=1.798, 95%
      CI=1.010-2.941, p=0.021). CONCLUSION: This study demonstrated that there is a
      correlation of +104T/C polymorphism in the 5'-UTR of GDF5 with knee OAin a
      Turkish population.

PMID- 29056120
TI  - Effects of Erdosteine on Experimental Acute Pancreatitis Model.
AB  - OBJECTIVE: To create acute pancreatitis condition experimentally in rats using
      cerulein, and to reveal histopathological effects in pancreatic tissue with
      erdosteine. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY:
      Department of General Surgery, Duzce University, Turkey, from June to October
      2014. METHODOLOGY: Thirty male Wistar albino rats were divided into three groups.
      No procedures were applied to Group 1. The rats in Group 2 and Group 3 were
      injected cerulein, to establish an experimental pancreatitis model and the blood
      amylase and lipase values were examined. The rats in Group 3 were given 10 mg/kg
      erdosteine. This treatment was continued for another 2 days and the rats were
      sacrificed. The pancreatic tissues were examined histopathologically for edema,
      inflammation, acinar necrosis, fat necrosis, and vacuolization. RESULTS: The
      lipase and amylase values and the histopathological examination of pancreatic
      tissues evidenced that the experimental acute pancreatitis model was established
      and edema, inflammation, acinar necrosis, fat necrosis, and vacuolization were
      observed in the pancreatic tissues. The statistical results suggest that
      erdosteine can decrease the edema, inflammation, acinar necrosis, fat necrosis
      and vacuolization scores in the tissues. CONCLUSION: The severity of acute
      pancreatitis, induced by cerulein in rats, is reduced with the use of erdosteine.

PMID- 29056121
TI  - Effectiveness of Ultrasound Shear for Clipless Laparoscopic Cholecystectomy
      Versus Conventional Unipolar Electrocautery in Patients with Cholelithiasis.
AB  - OBJECTIVE: To determine the efficacy of ultrasound shear in laparoscopic
      cholecystectomy in terms of total operative time, postoperative bile leaks, gall
      bladder perforation rate, and postoperative bleeding from cystic artery and
      collateral injury to bowel and duodenum. STUDY DESIGN: Comparative study. PLACE
      AND DURATION OF STUDY: Mayo Hospital, Lahore, from June 2013 to May 2014.
      METHODOLOGY: 150 cases (75 in each group) were randomized into two groups, i.e.
      harmonic scalpel clipless group (HSG) versus conventional laparoscopic
      cholecystectomy (CLC) with electrocautery group. The above stated variables were
      documented. The data for age, blood loss, and drain output were positively skewed
      as calculated using the Shapiro-Wilk test. The histograms, Q-Q plots and box
      plots were analyzed for all the dependent variables. Skewed qualitative
      continuous data was analyzed using the Mann-Whitney U-Test. RESULTS: Operative
      time was significantly lower in HSG as compared to CLC. Median operative times
      were 30 minutes (IQR 10) versus 35 minutes (IQR 10) (p<0.001). HSG group had
      perforation rate of 5/75 (6.67%) as compated to 16/75 (21.33%) in CLC (p=0.010).
      Intraoperative blood loss in group Awas significantly lower than in group B
      (p=0.001). Postoperative median pain score was 3 (IQR 2) versus 3 (IQR 3) in HSG
      versus CLC, respectively. CONCLUSION: All the primary outcomes showed improved
      results in the ultrasound shear group as compared to the group for conventional
      electrocautery.

PMID- 29056122
TI  - Total Versus Subtotal Gastrectomy for Signet Ring Cell Carcinoma of the Stomach.
AB  - OBJECTIVE: To determine the adequate surgery type for the treatment of signet
      ring cell of stomach in terms of postoperative complications and survival. STUDY
      DESIGN: Comparative analytical study. PLACE AND DURATION OF STUDY: Baskent
      University Adana Teaching and Research Center, Adana, Turkey, between 2006 and
      2015. METHODOLOGY: Atotal of 46 patients with the diagnosis of gastric signet
      ring cell, who underwent total or subtotal gastrectomy, were enrolled in this
      study. Patients were compared according to age, gender, tumor location, TNM
      stage, survival and mortality rates, operation time, complication and recurrence.
      Comparisons between groups were performed by using Mann-Whitney U-test for the
      data not normally distributed. The categorical data were analyzed by using the
      Chisquare test or Fisher's exact test, where applicable. Kaplan-Meier test was
      used for survival curve and Long-rank test was used for survival differences
      between groups. Values of p < 0.05 were considered statistically for all tests.
      RESULTS: Of the 46 patients, 29 (63.0%) were male. The mean age was 56.6 +/-13.2
      years. The median tumor size was 5.0 cm (IQR: 3.0-6.6). Twenty-six (56.5%)
      patients were in total gastrectomy, whereas 20 (43.5%) were in subtotal
      gastrectomy group. Five-year cumulative survival rate was 0.487. Five-year
      overall survival rate for early and advanced signet ring cell carcinoma was 0.830
      and 0.164, respectively (p<0.001). Five-year overall survival rate for total and
      subtotal gastrectomy groups were 0.422 and 0.582, respectively (P=0.417).
      Complications were observed in 17.4% (n=8) of all 46 patients. CONCLUSION:
      Subtotal gastrectomy can be performed safely for patients with gastric signet
      ring cell carcinoma and is equal to total gastrectomy with respect to prognosis
      and complication rates.

PMID- 29056123
TI  - Immunohistochemical Expression of CD10, BCL6 and MUM1 in Differentiating Diffuse
      Large B Cell Lymphoma Subtypes.
AB  - OBJECTIVE: To determine the immunohistochemical expression of CD10, BCL6 and MUM1
      in differentiating diffuse large B cell lymphoma subtypes. STUDY DESIGN:
      Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Department of
      Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from November
      2014 to May 2015. METHODOLOGY: Newly diagnosed cases of DLBCLon H&E stain as well
      as IHC markers, according to WHO blue book 2008, were included in the study.
      Patients' gender, age and site of lymphoma were noted. DLBCLsubtypes (GCB and
      activated type or non-GCB) were assessed based on IHC expression of CD10, BCL6
      and MUM1 and the results were recorded. The data were analyzed by using computer
      software program SPSS version 20. Descriptive statistics, frequencies and
      percentages were calculated. RESULTS: Out of 96 patients, 79 (82%) were male and
      17 (18%) were female. Mean age was 54.66 +/-16.73 years. Thirty-six (37.5%) cases
      showed positivity for CD10 and BCL6 both (GCB type), whereas MUM1 was positive in
      60 (62.5%) cases (non-GCB type or activated type). Asignificant statistical
      association was seen between expression of IHC markers (CD10, BCL6 and MUM1) and
      DLBCLsubtypes (GCB and non-GCB type, p<0.001). CONCLUSION: In Pakistani
      population, the frequency of non-GCB type expressing MUM1 is 62.5%, which is
      quite high as compared to western countries. It needs to be further explored,
      because it represents high-risk subsets in which alternative strategies for
      diagnosis and management should be planned.

PMID- 29056124
TI  - Association of ADIPOQ C-11377G (rs266729), TNF-alpha alphaG-308A(rs1800629) and
      TNF-alpha alphaG-238A(rs361525) Single Nucleotide Polymorphisms with Type 2
      Diabetes Mellitus in Pakistani Population.
AB  - OBJECTIVE: To determine the frequencies of adiponectin (ADIPOQ) C-11377G, tumor
      necrosis factor-alpha (TNF-alpha) G-308A and TNF-alphaG-238Asingle nucleotide
      polymorphisms (SNP) and their association with serum levels in Pakistani T2DM and
      healthy population. STUDY DESIGN: Case control study. PLACE AND DURATION OF
      STUDY: Military Hospital, Rawalpindi, Army Medical College and Institute of
      Biomedical and Genetic Engineering, Islamabad, Pakistan, from June 2012 till
      2014. METHODOLOGY: Cases (n=539) and controls (n=250) comprising of T2DM and
      healthy subjects, respectively, belonging to Pakistani Punjabi Rajput ethnicity
      were genotyped for SNPs. Serum adiponectin, TNF-alpha, insulin, blood sugar
      fasting (BSF), lipid profile, body mass index (BMI), and insulin resistance (IR)
      was determined and correlated with genotypes. RESULTS: Serum TNF-alphawas
      significantly higher and adiponectin was lower in T2DM than healthy controls (p <
      0.003 and 0.0001, respectively, Mann-Whitney U-test). The frequency of ADIPOQ CC,
      GC and GG was 340 (63.1%), 167 (31%) and 32 (5.9%) in T2DM patients. ADIPOQ 
      11377 SNPwas not significantly associated with T2DM [OR = 1.116 (95% CI
      0.811.53), p = 0.27- Fisher's exact test]. Genotypes deviated from Hardy-Weinberg
      equilibrium. Minor alleles of TNF-alphaG-308A and TNF-alphaG-238Awere not found
      in either groups. CONCLUSION: Frequency of ADIPOQ -11377 risk allele is low and
      does not functionally affect the serum adiponectin levels; hence, ADIPOQ C-11377G
      SNPis not a risk factor for T2DM in Pakistani Punjabi Rajput patients. Moreover,
      TNF-alphaG-308A and TNF-alphaG-238ASNPs are not prevalent in this ethnic group.

PMID- 29056125
TI  - Quantification and Further Refinements of Dorsal Metacarpal Artery Perforator
      Flap for Reconstruction of Wounds of Fingers upto Distal Interphalangeal Joints.
AB  - OBJECTIVE: To assess the outcome of dorsal metacarpal artery perforator flap for
      coverage of finger defects extending upto distal interphalangeal joint (DIPJ).
      STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Jinnah Burn and
      Reconstructive Surgery Centre, Lahore, from March 2015 to May 2017. METHODOLOGY:
      Our study was carried out in two parts. 1st part of study was to measure average
      flap length in our population. Five hundred cases were enrolled to measure flap
      length, from pivot point of the flap to the distal border of extensor
      retinaculum. This length was traced to fingers to determine its coverage area.
      This was followed by clinical study in 35 cases. All patients with wounds over
      dorsal surface of fingers upto distal interphalangeal joint and volar surface of
      fingers upto mid of middle phalanx, single or multiple finger defects with
      exposed tendon joints or bones were included in the study. Patients with history
      of trauma to the dorsum of hand, metacarpal head or neck fracture and patients
      with history of diabetes or peripheral vascular disease were excluded. RESULTS:
      Flap length decreased from radial to ulnar side of hand. Average length of flap
      based on the second metacarpal artery was 7cm while of the third was 6.6 cm and
      the fourth was 6.1 cm. This flap length covered upto mid of middle phalanx in
      border digits while upto PIPJ in central digits. This data was confirmed in 35
      patients in which 36 flaps were raised to cover finger defects. Thirty-four flaps
      survived completely while tip necrosis was seen in 2 cases. CONCLUSION: The
      dorsal metacarpal artery perforator flap is a thin, pliable flap, which has
      minimal donor-site morbidity. It can reliably cover soft tissue defects of dorsum
      of fingers upto mid of middle phalanx in border digits and upto PIPJ in central
      digits.

PMID- 29056126
TI  - Review Typology: The Basic Types of Reviews for Synthesizing Evidence for the
      Purpose of Knowledge Translation.
AB  - With advances in medical practice and fields of research, reviews occupy a key
      position for summarizing existing knowledge. Due to the differences and overlap
      in terminology, the full potential for reviews may be lost due to confusion of
      indistinct approaches. The main objective of this study was to provide a
      descriptive outline of each of the common review types with their characteristics
      and examples in a health care system. Ascoping search was conducted using the
      keywords associated with the literature review typology. The SALSA(Search,
      Appraisal, Synthesis and Analysis) analytical framework was used to identify and
      distinguish each type of review. Nine common types of reviews and associated
      methodologies were evaluated against the already established SALSA framework.
      Their description, strengths and weaknesses are presented. The results provided a
      basic idea of different types of reviews based on the intended level of knowledge
      synthesis by which researchers can identify the appropriate type of review based
      on their intended audience.

PMID- 29056127
TI  - Transverse Acetabular Ligament as an Anatomical Landmark for Intraoperative Cup
      Anteversion in Primary Total Hip Replacement.
AB  - OBJECTIVE: To assess the results of the use of transverse acetabular ligament
      (TAL) as an intraoperative indicator for acetabular cup anteversion alignment
      during total hip replacement. STUDY DESIGN: Case series. PLACE AND DURATION OF
      STUDY: The Nursing Home Hospital in Baghdad Medical City Complex, Baghdad, Iraq,
      from October 2014 to June 2015. METHODOLOGY: Patients were operated through a
      posterolateral approach for primary total hip arthroplasty (THA) in which
      transverse acetabular ligament (TAL) was identified and used as indicator for cup
      anteversion. Those with previous surgery and secondary osteoarthritis due to
      dysplasia or tumor were excluded. Postoperative anteversion angles were measured
      by using anteroposterior pelvic radiographs using Pardhan method by two different
      observers and the perceived quality of operative outcome was directly asked to
      the patient. RESULTS: There were a total of 31 patients. The anteversion angle
      ranged between 5.7 - 24.40 degrees . In addition, the calculated mean angle of
      14.7 degrees for the current study sample did not obviously or significantly
      depart from the required optimum angle of 15 degrees defined by Lewinnek (15 +/
      10 degrees , p=0.82). For the perceived quality of operative outcome, good
      outcome (satisfied) was expressed by two-thirds (67.7%) of study subjects after
      four weeks of surgery. CONCLUSION: Using transverse acetabular ligament as an
      intraoperative landmark is a simple, effective, and patientspecific method for
      proper cup anteversion placement in primary THA.

PMID- 29056128
TI  - Successful Treatment of Zenker's Diverticulum by Endoscopic Staple-Assisted
      Diverticulotomy in a 75-year Saudi Female.
AB  - Zenker's diverticulum (hypopharyngeal pouch) is a rare medical entity caused by
      herniation of esophageal mucosa and submucosa through an anatomical defect
      between the layers of the inferior constrictor muscle. It is believed that this
      occurs mainly due to incoordination between the stages of swallowing and timely
      opening of the cricopharyngeus. It usually affects the elderly and patients
      usually present with dysphagia, regurgitation of food, halitosis and aspiration.
      We describe one case of Zenker's diverticulum in a 75-year Saudi female whom we
      successfully managed in Ear Nose Throat (ENT) department, North West Armed Forces
      Hospital, Tabuk, Saudi Arabia by endoscopic staple-assisted diverticulotomy
      resulting in successful division of the intervening septum between the
      diverticulum and the esophagus. This technique was well-tolerated by the patient
      with early return to oral feeding and shorter hospital stay. Endoscopic staple
      assisted diverticulotomy is a relatively safer technique of dealing with this
      problem as compared to the traditional open procedure causing more morbidity, and
      we advocate its use to reduce patient morbidity in selected cases.

PMID- 29056129
TI  - Disseminated Infection with Multiple Cold Abscesses Caused by Rhizopus Arrhizusin
      an Immunocompetent Girl.
AB  - Although infections with fungi, such as Rhizopus species,usually occur in
      diabetics or immunocompromised patients, they can also rarely affect
      immunocompetent individuals. We present a case of disseminated infection with
      multiple cold abscesses in a 13-year, otherwise healthy girl caused by Rhizopus
      arrhizus.

PMID- 29056131
TI  - Late Presentation of Aggressive Fibromatosis Involving Head, Neck and Chest Wall.
AB  - Fibromatosis is a rare, benign, slow-growing and locally infiltrative tumour,
      caused by uncontrolled proliferation of fibrous tissue arising from muscles,
      connective tissue, fasciae and aponeurosis. It is also called desmoid tumour,
      which is very rare pathology representing only 0.03% of all neoplasms in human
      and around 3% of all soft tissue tumours. It is locally aggressive and usually
      invades the surrounding structures and has a high recurrence rate, even after
      surgical complete resection, which should be the first line of treatment. Here,
      we report a very rare case of extensive and disabling fibromatosis tumour in a 38
      year male, involving three compartments of the right side of the head, neck and
      chest wall, which was completely excised surgically and had excellent
      postoperative results with no morbidity.

PMID- 29056130
TI  - An Adult with Polyneuropathy and Hypogonadism due to Poems Syndrome.
AB  - POEMS (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein
      myeloma and skin changes), is a rare disease which occurs in the setting of
      plasma cell dyscrasias. We describe a case of an adult lady who presented with
      gradual onset weakness of all four limbs and multisystem involvement
      characterized by pedal edema, ascites, hyperpigmentation and hypogonadism. Nerve
      conduction study showed severe sensorimotor polyneuropathy. Serum immunofixation
      showed lambda light chain restricted monoclonal gammopathy. Bone marrow biopsy
      consistent with plasma cell dyscrasia. Hormonal assay showed decreased FSH, LH
      and estradiol levels which led us to diagnosis of hypogonadotrophic hypogonadism.
      The patient responded well to combination therapy of thalidomide, melphalan and
      dexamethasone. Eight months after the therapy, she noted decreased paresthesias
      and increased strength. She had reduced edema and ascites.

PMID- 29056132
TI  - Nedaplatin-Induced Arrhythmia: Retrospective Analysis of Three Cases.
AB  - Nedaplatin (NDP) is a second-generation platinum derivative that was developed in
      Japan. Nowadays, it is being widely used in the management of lung cancer,
      esophageal cancer, head and neck cancers, especially when cisplatin and
      carboplatin cannot be tolerated or show drug resistance. To the best of our
      knowledge, there are few reported cases of NDP-induced bradycardia in the
      relevant medical literature. The current report presents three patients treated
      with NDP chemotherapy-induced serious arrhythmias. The three cases developed
      sinus tachycardia and atrial premature beats, complete left bundle branch block,
      and bigeminy ventricular premature contraction, in the second, sixth and second
      cycle, respectively. No one died of cardiac toxicity. These were treated with
      dexamethasone, 5 mg intravenous injection and diphenhydramine 20 mg,
      intramuscular injection. The heart rhythm returned to normal in 30 minutes, a
      day, and four days, respectively.

PMID- 29056134
TI  - Telehealth: Trend in Pakistan.

PMID- 29056133
TI  - Polymeric Clips for Stump Closure in Laparoscopic Appendectomy.
AB  - Many different techniques are used to perform laparoscopic appendectomy in terms
      of locations of trocars and closure of the appendiceal stump. They include
      mechanical endostaplers, endoligature, metal clips, bipolar endocoagulation,
      polymeric clips and intracorporeal sutures. The method of choice for appendiceal
      stump closure should be inexpensive and easy to perform. Non-absorbable polymer
      clips is an acceptable option for this purpose. Polymeric clips provide
      considerable cost savings as compared with endoscopic staplers, and are easy to
      apply in comparison to suture ligature techniques. In this study, we aimed to
      investigate outcomes of appendectomy carried out by using polymeric clips in 123
      patients without any intraabdominal collection of pus or abscess. As such, the
      authors found polymeric clips to be safe, cheap and effective for stump closure
      in laparoscopic appendectomy.

PMID- 29056135
TI  - Polymorphous Low Grade Adenocarcinoma of Hard Palate: AHistopathological
      Pictorial.

PMID- 29056136
TI  - A Resident's Note.

PMID- 29056137
TI  - Cavernous Hemangioma of the Auricle.

PMID- 29056138
TI  - Teaching Basic Pediatric Intensive Care Course to Pediatric Residents and
      Consultants.

PMID- 29056139
TI  - Advancement of House Flap in Treatment of Perianal Basal Cell Carcinoma.

PMID- 29056140
TI  - Introduction to Northeast Pacific Shark Biology, Research, and Conservation, Part
      B.
AB  - Sharks are iconic, sometimes apex, predators found in every ocean. Because of
      their ecological role as predators and concern over the stability of their
      populations, there has been an increasing amount of work focused on shark
      conservation around the world in recent decades. The populations of sharks that
      reside in the Northeast Pacific (NEP) Ocean bordering the west coast of the
      United States reside in one of the most economically and ecologically important
      oceanic regions in the world. Volume 78 of Advances in Marine Biology (AMB) is a
      companion to Volume 77, which focused primarily on NEP shark biodiversity,
      organismal biology, and ecology. Volume 78 highlights fisheries and the
      conservation implications of fisheries management; shark population modelling and
      the conservation impacts of these models given that many life history metrics of
      NEP sharks necessary to accurately run these models are still unknown; the value
      of captive sharks to the biology, outreach, and conservation of NEP sharks; and
      the conservation value of citizen science and shark ecotourism. Together these
      volumes encapsulate the current state of the knowledge for sharks in the NEP and
      lay the foundation for protecting, managing, and learning from these species in
      the face evolving natural conditions and societal opinions.

PMID- 29056141
TI  - The Economy of Shark Conservation in the Northeast Pacific: The Role of
      Ecotourism and Citizen Science.
AB  - Historically sharks have been seen either as a source of income through
      harvesting, or as a nuisance and danger. The economic value of sharks has
      traditionally been measured as the total value of sharks caught for liver oil,
      fins, or meat for consumption. Sharks have also been killed to near extinction in
      cases where they were seen as a threat to fisheries on other species. This is
      illustrated by the mass extermination of Basking Sharks (Cetorhinus maximus) in
      British Columbia. They were seen as a nuisance to fishermen as they got entangled
      in gill nets during the salmon fishing season. However with the development of
      the SCUBA diving industry, and ecotourism in general, increased awareness of the
      role sharks play in marine ecosystems has resulted in changes in how they are
      perceived and utilized. Despite an ongoing harvest of sharks such as the North
      Pacific Spiny Dogfish (Squalus suckleyi), sharks now generate economic value
      through SCUBA diving enthusiasts who travel the globe to see, swim with, and
      photograph them. The use of digital cameras and other digital media has brought
      sharks into households around the world and increased awareness of the
      conservation issues facing many species. This renewed appreciation has led to a
      better understanding of sharks by the public, resulting in advocates calling for
      better protections and conservation. In particular, a growing part of the SCUBA
      diving community wants to contribute to conservation and research projects, which
      has led to participation in citizen science projects. These projects provide
      scientific data but also gain ground as ecotourism activities, thus adding to
      both economic value of tourism and conservation efforts.

PMID- 29056142
TI  - Conclusions: The Future of Shark Management and Conservation in the Northeast
      Pacific Ocean.
AB  - Human interactions with sharks in the Northeast Pacific Ocean (NEP) have occurred
      for millennia but were largely limited to nearshore encounters as target and
      nontarget catch in fisheries. The arrival of Spanish explorers in the mid-1500s,
      followed by subsequent waves of explorers and colonizers from Europe and Russia,
      did little to change this relationship, until the mid-1800s. As technological
      advances conferred the ability to exploit marine fish further offshore and in
      deeper water, substantial fisheries developed and many of these encountered, and
      sometimes directly targeted, sharks. As these fisheries rose and fell with market
      demands and fluctuations in the abundance of target species, the collective
      consciousness of the nations fishing this region came to realize that adequate
      management plans with clear policy guidance rooted in conservation were crucial
      to sustaining both biodiversity and abundance of marine resources. With
      explicitly defined management regions governed by scientifically informed bodies
      that consider both societal and ecological needs, systems have been in place to
      manage and conserve marine species, including sharks, for over four decades now
      in the NEP. While policy evolution has largely limited directed fishing pressure
      as a threat for most shark species, bycatch is still a concern. Additionally,
      habitat degradation and destruction, ocean acidification, and global climate
      change are anticipated to fundamentally alter the ecosystems sharks are an
      integral part of in coming decades and centuries. Adequate conservation and
      management of sharks in the NEP, and around the world, moving into this period of
      uncertainty will rely upon comprehensive, integrated management of the ecosystem
      rooted in international coordination and cooperation. Far from being an
      unattainable goal, steps are being made each day to 'move the needle' in this
      direction-for the benefit of all.

PMID- 29056143
TI  - An Introduction to Modelling Abundance and Life History Parameters in Shark
      Populations.
AB  - Elasmobranchs play critically important ecological roles throughout the world's
      oceans, yet in many cases, their slow life histories and interactions with
      fisheries makes them particularly susceptible to exploitation. Management for
      these species requires robust scientific input, and mathematical models are the
      backbone of science-based management. In this chapter, we provide an introductory
      overview of the use of mathematical models to estimate shark abundance. First, we
      discuss life history models that are used to understand the basic biology of
      elasmobranchs. Second, we cover population dynamics models, which are used to
      make inferences regarding population trend, size, and risk of extinction.
      Finally, we provide examples of applied models used to assess the status of
      elasmobranchs in the Northeast Pacific Ocean to guide management for these
      species. This chapter is not a comprehensive review of quantitative methods, but
      rather introduces various mathematical tools in fisheries management, with a
      focus on shark management in the Northeast Pacific Ocean.

PMID- 29056144
TI  - Sharks in Captivity: The Role of Husbandry, Breeding, Education, and Citizen
      Science in Shark Conservation.
AB  - The role of public aquariums in promoting conservation has changed substantially
      over the decades, evolving from entertainment attractions to educational and
      research centres. In many facilities, larger sharks are an essential part of the
      collection and represent one of the biggest draws for the public. Displaying
      healthy elasmobranchs comes with many challenges, but improvements in husbandry
      techniques have enabled aquariums to have success with a variety of species. The
      establishment of organisations such as the Association of Zoos and Aquariums, and
      the completion of texts like the Elasmobranch Husbandry Manual, has helped set
      high standards of care for sharks in captivity and promoted international
      conservation efforts. Aquariums keeping sharks are in a unique position to
      influence local, regional, and international attitudes and policies by acting as
      both educational and research facilities. Interactions with multiple stakeholders
      of diverse educational and demographic backgrounds through the use of in-house
      advocacy, public outreach, media interviews, and partnerships with academic and
      government institutions enable these facilities to engage and share information
      with a broad audience. Although the data collected on sharks in captivity often
      cannot be directly translated to animals in the wild, it offers better insight
      into a number of life history traits and poorly understood behaviours, and has
      been the foundation for many captive breeding programs. Several Northeast Pacific
      (NEP) shark species are commonly displayed for long durations or bred in
      aquariums, while other less studied species have been held for short periods to
      collect valuable data that can be applied towards ongoing studies and
      conservation measures. Here, we discuss past and current tangible benefits of
      holding NEP sharks in captivity, as well as noting several ways in which future
      research and education activities will continue to inform and shape public
      opinions on shark management and conservation.

PMID- 29056145
TI  - Shark Interactions With Directed and Incidental Fisheries in the Northeast
      Pacific Ocean: Historic and Current Encounters, and Challenges for Shark
      Conservation.
AB  - For over 100 years, sharks have been encountered, as either directed catch or
      incidental catch, in commercial fisheries throughout the Northeast Pacific Ocean.
      A long-standing directed fishery for North Pacific Spiny Dogfish (Squalus
      suckleyi) has occurred and dominated shark landings and discards. Other
      fisheries, mainly for shark livers, have historically targeted species including
      Bluntnose Sixgill Shark (Hexanchus griseus) and Tope Shark (Galeorhinus galeus).
      While incidental catches of numerous species have occurred historically, only
      recently have these encounters been reliably enumerated in commercial and
      recreational fisheries. In this chapter we present shark catch statistics
      (directed and incidental) for commercial and recreational fisheries from Canadian
      waters (off British Columbia), southern US waters (off California, Oregon, and
      Washington), and northern US waters (off Alaska). In total, 17 species of sharks
      have collectively been encountered in these waters. Fishery encounters present
      conservation challenges for shark management, namely, the need for accurate catch
      statistics, stock delineation, life history parameter estimates, and improved
      assessments methods for population status and trends. Improvements in management
      and conservation of shark populations will only come with the further development
      of sound science-based fishery management practices for both targeted and
      incidental shark fisheries.

PMID- 29056146
TI  - Corrigendum to 'Evaluation of the cytotoxicity, genotoxicity and mucus permeation
      capacity of several surface modified poly(anhydride) nanoparticles designed for
      oral drug delivery' [International Journal of Pharmaceutics 517 (2017) 67-79].

PMID- 29056147
TI  - Corrigendum to: EXPLOITING THE VERSATILITY OF CHOLESTEROL IN NANOPARTICLES
      FORMULATION (International Journal of Pharmaceutics. 511 (1) (2016) 331-340).

PMID- 29056148
TI  - Neuropeptides and Addiction: An Introduction.
AB  - Neuropeptides are short sequences of amino acids that are coexpressed with
      neurotransmitters and which are widely expressed throughout the central nervous
      system. There is a large database of data pointing to critical roles for
      neuropeptides in modulating neurobiological responses to alcohol and drugs of
      abuse. Continued alcohol and drug use promote allostatic alterations in
      neuropeptide systems, and these changes contribute to excessive and uncontrolled
      intake that emerges with dependence. The neuropeptides that are reviewed in this
      chapter represent some of the most well-studied targets in the current drug and
      alcohol abuse literature. The goal of this chapter is to convey the significant
      roles that neuropeptides play in neurobiological responses to alcohol and drugs
      of abuse, and reinforce the idea that targeting neuropeptides and their receptors
      continue to be attractive avenues for treating drug and alcohol use disorders, as
      well as eating disorders.

PMID- 29056149
TI  - The Role of the Melanocortin System in Drug and Alcohol Abuse.
AB  - The melanocortin (MC) system is composed of different peptides centrally produced
      by proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus (N.Arc)
      and the medulla. These peptides act through five subtypes of melanocortin
      receptors (MCRs) that belong to the family of seven-transmembrane G-protein
      coupled receptors that are coupled through Galphas signaling pathways. MC3R and
      MC4R are the predominant MCR subtypes in the brain, and they are widely expressed
      in brain regions thought to modulate drug self-administration, including the
      nucleus accumbens, the hypothalamus, and the ventral tegmental area. The MC
      system is unique in terms of having an endogenous antagonist/inverse agonist,
      agouti-related protein (AgRP), also produces in the N.Arc and secreted in
      terminals expressing MCRs. There is a large body of research showing the role of
      the MC and AgRP systems in neurobiological responses to drugs of abuse, in
      particular, neurobiological responses to ethanol. In this chapter, we discuss the
      most recent evidence that supports the role of the MC/AgRP systems in modulating
      neurobiological responses to drugs of abuse, with a focus on ethanol consumption.

PMID- 29056150
TI  - Substance P and the Neurokinin-1 Receptor: The New CRF.
AB  - Substance P (SP) is an 11-amino acid neuropeptide of the tachykinin family that
      preferentially activates the neurokinin-1 receptor (NK1R). First isolated 85
      years ago and sequenced 40 years later, SP has been extensively studied. Early
      studies identified a role for SP and the NK1R in contraction of intestinal smooth
      muscle, central pain processing, and neurogenic inflammation. An FDA-approved
      NK1R antagonist, aprepitant, is used clinically for the treatment of chemotherapy
      induced nausea, as the NK1R influences the activity of the brain stem emesis
      centers. More recently, SP and the NK1R have gained attention for their role in
      complex psychiatric processes including stress, anxiety, and depression. However,
      clinical development of NK1R antagonists for these indications has so far been
      unsuccessful. Several preclinical studies have also demonstrated a role of the
      NK1R in drug taking and drug seeking, especially as it relates to escalated
      consumption and stress-elicited seeking. This line of research developed in
      parallel with findings supporting a role of corticotropin-releasing factor (CRF)
      in stress-induced drug seeking. Over this time, CRF arguably gained more
      attention as a target for development of addiction pharmacotherapies. However,
      this effort has not resulted in a viable drug for use in human populations. Given
      promising clinical findings for the efficacy of NK1R antagonists on craving in
      alcoholics, along with recent data suggesting that a number of negative results
      from NK1R trials were likely due to insufficient receptor occupancy, the NK1R
      merits being revisited as a target for the development of novel
      pharmacotherapeutics for addiction.

PMID- 29056151
TI  - The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders.
AB  - Neuropeptide Y (NPY) is a neuromodulator that is widely expressed throughout the
      central nervous system (CNS) and which is cosecreted with classic
      neurotransmitters including GABA and glutamate. There is a long history of
      research implicating a role for NPY in modulating neurobiological responses to
      alcohol (ethanol) as well as other drugs of abuse. Both ethanol exposure and
      withdrawal from chronic ethanol have been shown to produce changes in NPY and NPY
      receptor protein levels and mRNA expression in the CNS. Importantly,
      manipulations of NPY Y1 and Y2 receptor signaling have been shown to alter
      ethanol consumption and self-administration in a brain region-specific manner,
      with Y1 receptor activation and Y2 receptor blockade in regions of the extended
      amygdala promoting robust reductions of ethanol intake. Similar observations have
      been made in studies examining neurobiological responses to nicotine,
      psychostimulants, and opioids. When taken together with observations of potential
      genetic linkage between the NPY system and the human alcohol abuse disorders, NPY
      represents a promising target for treating problematic alcohol and drug use, and
      in protecting individuals from relapse during abstinence.

PMID- 29056153
TI  - Oxytocin, Tolerance, and the Dark Side of Addiction.
AB  - Substance use disorders blight the lives of millions of people and inflict a
      heavy financial burden on society. There is a compelling need for new
      pharmacological treatments as current drugs have limited efficacy and other major
      drawbacks. A substantial number of animal and recent clinical studies indicate
      that the neuropeptide, oxytocin, is a particularly promising therapeutic agent
      for human addictions, especially alcohol use disorders. In preliminary trials, we
      found that oxytocin administered by the intranasal route, which produces some
      neuropeptide penetration into the CNS, potently blocked withdrawal and reduced
      alcohol consumption in heavy drinkers. A considerable body of earlier animal
      studies demonstrated that oxytocin inhibits tolerance to alcohol, opioids, and
      stimulants as well as withdrawal from alcohol and opioids. Based on these
      preclinical findings and our clinical results, we hypothesize that oxytocin may
      exert therapeutic effects in substance dependence by the novel mechanism of
      diminishing established tolerance. A newer wave of studies has almost unanimously
      found that oxytocin decreases self-administration of a number of addictive
      substances in several animal models of addiction. Reduction of established
      tolerance should be included among the potential explanations of oxytocin effects
      in these studies and changes in tolerance should be examined in future studies in
      relationship to oxytocin influences on acquisition and reinstatement of self
      administration as well as extinction of drug seeking. Oxytocin efficacy in
      reducing anxiety and stress responses as well as established tolerance suggests
      it may be uniquely effective in reducing negative reinforcement (Koob's "dark
      side" of addiction) that maintains chronic substance use.

PMID- 29056154
TI  - Contribution of Urocortin to the Development of Excessive Drinking.
AB  - The corticotropin-releasing factor (CRF) system plays a role in alcohol
      consumption, and its dysregulation can contribute to alcohol use disorder. This
      system includes four peptide ligands: CRF, urocortin (Ucn)1, Ucn2, and Ucn3.
      Historically, attention focused on CRF, however, Ucn1 also plays a critical role
      in excessive alcohol use. This review covers evidence for this contribution and
      contrasts the role of Ucn1 with CRF. While CRF can promote binge consumption,
      this regulation occurs through generalized mechanisms that are not specific for
      alcohol. In contrast, inhibition of Ucn1 action specifically blunts escalation of
      alcohol drinking. Lesions, genetic knockout, and RNA interference experiments
      indicate that the centrally projecting Edinger-Westphal nucleus is the
      neuroanatomical source of Ucn1 critical for alcohol drinking. We propose that the
      contributions of Ucn1 to excessive drinking likely occur through enhancing
      rewarding properties of alcohol and symptoms of alcohol withdrawal, whereas CRF
      drives dependence-induced drinking at later stages of alcohol use. The transition
      from occasional binge drinking to dependence intricately depends on CRF system
      plasticity and coordination of CRF and Ucn1.

PMID- 29056152
TI  - Orexin/Hypocretin System: Role in Food and Drug Overconsumption.
AB  - The neuropeptide orexin/hypocretin (OX), while largely transcribed within the
      hypothalamus, is released throughout the brain to affect complex behaviors.
      Primarily through the hypothalamus itself, OX homeostatically regulates adaptive
      behaviors needed for survival, including food intake, sleep-wake regulation,
      mating, and maternal behavior. However, through extrahypothalamic limbic brain
      regions, OX promotes seeking and intake of rewarding substances of abuse, like
      palatable food, alcohol, nicotine, and cocaine. This neuropeptide, in turn, is
      stimulated by the intake of or early life exposure to these substances, forming a
      nonhomeostatic, positive feedback loop. The specific OX receptor involved in
      these behaviors, whether adaptive behavior or substance seeking and intake, is
      dependent on the particular brain region that contributes to them. Thus, we
      propose that, while the primary function of OX is to maintain arousal for the
      performance of adaptive behaviors, this neuropeptide system is readily co-opted
      by rewarding substances that involve positive feedback, ultimately promoting
      their abuse.

PMID- 29056156
TI  - Dynorphin/Kappa Opioid Receptor Signaling in Preclinical Models of Alcohol, Drug,
      and Food Addiction.
AB  - The dynorphin/kappa opioid receptor (KOR) system is implicated in the "dark side"
      of addiction, in which stress exacerbates maladaptive responses to drug and
      alcohol exposure. For example, acute stress and acute ethanol exposure result in
      an elevation in dynorphin, the KOR endogenous ligand. Activation of KORs results
      in modulation of several neurotransmitters; however, this chapter will focus on
      its regulatory effects on dopamine in mesolimbic areas. Specifically, KOR
      activation has an inhibitory effect on dopamine release, thereby influencing
      reward processing. Repeated stimulation of KORs, for example, via chronic drug
      and/or stress exposure, results in increased function of the dynorphin/KOR
      system. This augmentation in KOR function shifts the homeostatic balance in favor
      of an overall reduction in dopamine signaling via either by reducing dopamine
      release or by increasing dopamine transporter function. This chapter examines the
      effects of chronic ethanol exposure on KOR function and the downstream effects on
      dopamine transmission. Additionally, the impact of chronic cocaine exposure and
      its effects on KOR function will be explored. Further, KORs may also be involved
      in driving excessive consumption of food, contributing to the risk of developing
      obesity. While some studies have shown that KOR agonists reduce drug intake,
      other studies have shown that antagonists reduce addiction-like behaviors,
      demonstrating therapeutic potential. For example, KOR inhibition reduces ethanol
      intake in dependent animals, motivation to self-administer cocaine in chronic
      stress-exposed animals, and food consumption in obese animals. This chapter will
      delve into the mechanisms by which modulation of the dynorphin/KOR system may be
      therapeutic.

PMID- 29056157
TI  - The Role of the Ghrelin System in Drug Addiction.
AB  - In the past years, a significant volume of research has implicated the appetitive
      hormone ghrelin in the mechanisms underlying drug use and addiction. From a
      neuroscientific standpoint, ghrelin modulates both reward and stress pathways,
      two key drivers of substance use behaviors. Previous investigations support a
      connection between the ghrelin system and alcohol, stimulants, and tobacco use in
      both animals and humans, while the research on opioids and cannabis is scarce. In
      general, upregulation of the ghrelin system seems to enhance craving for drugs as
      well as substances use. On the other hand, acute and chronic exposure to drugs of
      abuse influences the ghrelin system at different levels. This chapter summarizes
      the literature on the relationship between the ghrelin system and substance
      related behaviors. We also review recent work investigating the ghrelin system as
      a potential pharmacological target for treating substance use disorders and
      discuss the need for additional research.

PMID- 29056158
TI  - Preface.

PMID- 29056159
TI  - Should We Recommend Renal Diet-Related Apps to Our Patients? An Evaluation of the
      Quality and Health Literacy Demand of Renal Diet-Related Mobile Applications.
AB  - OBJECTIVE: Mobile phone applications (apps) are increasingly being used by
      patients with chronic kidney disease (CKD). We sought to describe the main
      purpose of commonly available renal diet apps and to quantify the accuracy of
      information, technical quality, and health literacy demand of renal diet apps.
      DESIGN: The design was content analysis. All eligible renal diet apps in the
      Australian Apple App Store, Google Play, Windows Phone, and Blackberry App World
      were evaluated. SUBJECTS: Eligible apps were in English and were related to
      kidney disease in humans (of any type or stage). Exclusion criteria included apps
      which were prohibited because of password protection. MAIN OUTCOME MEASURE: Renal
      diet information in the apps was compared with evidence-based guidelines for the
      management of kidney disease to quantify information accuracy. App information
      was evaluated using the Silberg Scale. Technical quality and health literacy
      demand were evaluated using the Mobile Application Rating Scale. RESULTS: A total
      of 21 apps were eligible for evaluation. The main purpose of these apps was to
      provide food and nutrition information (57.1%) or for educative purposes for CKD
      patients (38.1%). Only 47.6% (10/21) of apps contained accurate evidence-based
      information. Overall, app technical quality was considered acceptable (mean
      Mobile Application Rating Scale score 3.19 +/- 0.35 out of 5), with 80.9% of apps
      scoring acceptable or greater for app technical quality. Scores for health
      literacy demand also indicated that most apps (15/21, 71.4%) were acceptable.
      CONCLUSIONS: A range of apps currently exist that may provide individuals with
      CKD with useful food and nutrition information or increase their knowledge of the
      renal diet. These apps are also mainly of acceptable technical quality and health
      literacy demand. However, caution is required when using renal diet apps because
      more than half of the apps evaluated were not accurate and evidence based.

PMID- 29056160
TI  - Author's Reply to Letter to the Editor.

PMID- 29056155
TI  - Corticotropin-Releasing Factor (CRF) and Addictive Behaviors.
AB  - Drug addiction is a complex disorder that is characterized by compulsivity to
      seek and take the drug, loss of control in limiting intake of the drug, and
      emergence of a withdrawal syndrome in the absence of the drug. The transition
      from casual drug use to dependence is mediated by changes in reward and brain
      stress functions and has been linked to a shift from positive reinforcement to
      negative reinforcement. The recruitment of brain stress systems mediates the
      negative emotional state produced by dependence that drives drug seeking through
      negative reinforcement mechanisms, defined as the "dark side" of addiction. In
      this chapter we focus on behavioral and cellular neuropharmacological studies
      that have implicated brain stress systems (i.e., corticotropin-releasing factor
      [CRF]) in the transition to addiction and the predominant brain regions involved.
      We also discuss the implication of CRF recruitment in compulsive eating
      disorders.

PMID- 29056161
TI  - "Ephidrosis," Is a New Term to Replace the Term "Diaphoresis".

PMID- 29056162
TI  - Proceedings of the Ninth International Congress of Uremia Research and Toxicity.

PMID- 29056163
TI  - A History of Uremia Research.
AB  - The history of uremia research begins with the discovery of urea and the
      subsequent association of elevated blood urea levels with the kidney disease
      described by Richard Bright, a well told story that needs no recounting. What
      this article highlights is how clinical and laboratory studies of urea launched
      the analysis of body fluids, first of urine and then of blood, that would beget
      organic chemistry, paved the way for the study of renal function and the use of
      urea clearance to determine "renal efficiency," provided for the initial
      classification of kidney disease, and clarified the concepts of diffusion and
      osmosis that would lead to the development of dialysis. Importantly and in
      contrast to how the synthesis of urea in the laboratory heralded the death of
      "vitalism," the clinical use of dialysis restored the "vitality" of comatose
      unresponsive dying uremic patients. The quest for uremic toxins that followed has
      made major contributions to what has been facetiously termed "molecular
      vitalism." In the course of these major achievements derived from the study of
      urea, the meaning of "what is life" has been gradually liberated from its past
      attribution to supernatural forces (vital spirit, archaeus, and vital force)
      thereby establishing the autonomy of biological life in which the kidney is the
      master chemist of the living body.

PMID- 29056164
TI  - ADAM17, a New Player in the Pathogenesis of Chronic Kidney Disease-Mineral and
      Bone Disorder.
AB  - The triad composed by alpha-Klotho, fibroblast growth factor-23, and its receptor
      are involved in the pathogenesis of chronic kidney disease-mineral and bone
      disorder. A disintegrin and metalloproteinase 17 (ADAM17) is a metalloproteinase
      causing the proteolytic shedding of alpha-Klotho from the cell membrane, and its
      role in chronic kidney disease-mineral and bone disorder is not yet known. We
      studied the circulating levels of the above-mentioned mediators in patients with
      secondary hyperparathyroidism due to uremia, compared to control subjects, as
      well as in patients with primary hyperparathyroidism. We also measured the
      immunofluorescence pattern of the relevant tissue proteins in specimens obtained
      from patients undergoing parathyroid surgery for secondary compared to primary
      hyperparathyroidism. Results showed that alpha-Klotho tissue levels are reduced,
      in the presence of increased ADAM17 tissue levels. In addition, we showed
      increased serum levels of the main product of ADAM17 proteolytic activity, tumor
      necrosis factor-alpha. Thus, we found a paradoxical situation, in secondary
      compared to primary hyperparathyroidism, that is, that in the face of increased
      tumor necrosis factor-alpha in circulation, both soluble and tissue alpha-Klotho
      are reduced significantly, despite increased tissue ADAM17. In conclusion, tissue
      and serum levels of alpha-Klotho seem to have become independent from the
      regulation induced by ADAM17, which constitutes therefore another tassel in the
      impaired alpha-Klotho-FGF23 receptor axis present in uremia.

PMID- 29056165
TI  - The Leaky Gut and Altered Microbiome in Chronic Kidney Disease.
AB  - Chronic kidney disease results in disruption of the intestinal epithelial barrier
      as well as profound changes in the gut microbial flora. These events are largely
      mediated by (1) heavy influx of circulating urea to the gut lumen and (2) dietary
      restrictions of foods containing high fiber (such as fruits and vegetable) and
      symbiotic organisms (such as yogurt and cheese) imposed to mitigate hyperkalemia
      and hyperphosphatemia. Collectively, these factors promote systemic inflammation
      and cardiovascular morbidity by mediating microbial dysbiosis, disruption of the
      intestinal epithelial barrier, and translocation of endotoxin, bacterial
      fragments, and uremic toxins across the "leaky gut" into the bloodstream.
      Strategies aimed at increasing dietary fiber and lowering urea burden may help to
      attenuate uremia-induced microbial dysbiosis and epithelial barrier breakdown,
      and thereby improve systemic inflammation.

PMID- 29056166
TI  - Long-term Adverse Events Associated With Acute Kidney Injury.
AB  - Acute kidney injury (AKI) occurs in approximately 10% to 15% of hospital-admitted
      patients and is associated with in-hospital mortality of 50% in patients
      requiring renal replacement therapy. Recently, multiple observational studies
      have demonstrated that patients who survive AKI have significant long-term
      consequences including cardiovascular events, progression to advanced-stage
      chronic kidney disease (CKD), and mortality. A direct link between AKI and CKD is
      provided by studies that demonstrate that some patients with normal renal
      function who develop AKI requiring dialysis never recover. In addition, in a
      large pediatric AKI population, 10% of the cohort developed CKD within 1 to 3
      years. In a systemic review and meta-analysis in which 13 cohort studies were
      analyzed, patients with AKI had a hazard ratio (HR) of 8.8 for developing CKD, HR
      of 3.1 of developing end-stage kidney disease, and HR of 2.0 for mortality. AKI
      was also independently associated with risk for cardiovascular disease and
      congestive heart failure. These studies indicate that AKI is associated with
      important, long-term consequences and that AKI has become an important
      contributor to the end-stage kidney disease population. Prospective ongoing
      studies will better define the cause-effect relationship and delineate potential
      biomarkers that would identify AKI patients at risk for CKD, cardiovascular
      events, and mortality.

PMID- 29056167
TI  - Skin Blood Flow and Vascular Endothelium Function in Uremia.
AB  - Prevalence of dermatological disorder in patients with end-stage kidney disease
      is estimated as 50% to 100% in various studies. Some of the skin lesions are
      specific for the diseases causing chronic kidney disease (CKD), some are
      associated with CKD, and still others are the dermatological manifestation of
      uremia. Microangiopathy was also found in both arterioles and venule in the skin
      biopsy of "normal looking" skin in patients with end-stage kidney disease. In a
      cross-sectional study in patients on dialysis, we measured skin blood flow (SBF)
      using laser Doppler device in a standardized way at various areas of lower
      extremities at 2 different local skin temperatures: 35 degrees C and 44 degrees
      C. Local heating increases skin perfusion by mechanisms dependent on nitric oxide
      (NO). SBF was impaired in CKD patients Stage 5 on HD, particularly in those with
      diabetes mellitus as a cause of CKD. The reduced response in the SBF to the heat
      in our patients may be due to decreased generation of NO in uremia. Endothelium
      dependent vasodilatation in patients on dialysis and the response of the skin
      microcirculation to acetylcholine was diminished in hypertensive patients on
      dialysis. Similarly, patients with diabetes mellitus had decreased SBF during
      intradermal microdialysis with a NO synthase inhibitor. Multiple uremic toxins
      have been studied in vitro and show to cause various degree of endothelial cell
      dysfunction. Unfortunately, no clear benefit has been described in CKD patients
      to different intervention aimed to reduce uremic toxin effect on endothelium.
      There are no long-term data on the factors which can modify endothelium function
      in uremia, but non pharmacologic interventions, diet, and several pharmacologic
      approaches could be beneficial. Measurement of SBF can be useful in evaluation of
      vasculopathy in CKD population and can potentially be used for assessment of
      vascular response during specific clinical intervention.

PMID- 29056168
TI  - Cystic Fibrosis: A Risk Condition for Renal Disease.
AB  - OBJECTIVE: Cystic fibrosis (CF) is the most common autosomal recessive disease
      affecting the Caucasian population, with a birth incidence ranging between
      1:2,500 and 1:1,800. It is caused by mutations in the CF transmembrane regulator
      gene which is localized on 7 chromosomes. Renal disease is reported as a
      relatively rare complication in adult patient with CF. We evaluated proteinuria
      and chronic renal failure (CRF) in a population of patients with CF. METHODS: A
      retrospective study was carried out in a referral center for CF at University of
      Messina in Italy. We identified all patients with renal disease, characterized by
      proteinuria and/or CRF, during the period 2007 to 2012 and reviewed their medical
      records to assess influence on renal disease of genotype, number of pulmonary
      exacerbation, pancreatic insufficiency, pulmonary function, CF-related diabetes,
      and antibiotics courses. RESULTS: From a population of 77 adult patients with CF,
      we identified 9 patients with proteinuria (11.7%), and 11 patients (14.28%) with
      CRF. Mean age was 35.6 (+5.1 standard deviation) years, 55% were female and 33%
      had diabetes mellitus. Renal biopsy was performed in 3 patients because of
      nephrotic syndrome in 1 patient and proteinuria with renal failure in the other 2
      patients. Renal amyloidosis was disclosed in 2, whereas IgA nephropathy in 1
      patient. The DeltaF508 mutation in homozygosis was present in 44% of patients
      with proteinuria (vs. 27% of our CF population, relative risk 2.07), whereas
      genotype DeltaF508/N1303K in 22%. DeltaF508 allele mutation was present in 77.7%
      of proteinuric patients. CONCLUSIONS: Our study shows a higher prevalence of
      renal disease in patients with CF, than was previously described. The main reason
      may be related to increased life expectancy because of better management.
      Moreover, patients with DeltaF508 homozygosis had higher risk of proteinuria.

PMID- 29056169
TI  - Unacylated Ghrelin: A Novel Regulator of Muscle Intermediate Metabolism With
      Potential Beneficial Effects in Chronic Kidney Disease.
AB  - In patients with chronic kidney disease (CKD), malnutrition with loss of skeletal
      muscle mass has a negative impact on morbidity and mortality. Emerging evidence
      indicates that a cluster of oxidative stress, inflammation, and insulin
      resistance directly contributes to skeletal muscle catabolism by favoring protein
      breakdown over synthesis. Ghrelin is a gastric hormone discovered and initially
      studied in its acylated orexigenic form. More recently, a role of unacylated
      ghrelin (UnAG) has been described to reduce skeletal muscle mitochondrial
      reactive oxygen species generation, inflammation, and insulin resistance both in
      experimental models and in clinical studies. UnAG administration could therefore
      represent a potential comprehensive therapeutic approach for CKD-related
      metabolic and nutritional complications. Studies of UnAG administration in
      experimental and clinical CKD are needed to test the hypothesis that UnAG may
      chronically improve nutritional status and outcome in CKD patients.

PMID- 29056170
TI  - Sister Earth, Our Common Home: Toward a Sustainable, Planet Friendly Approach to
      Dialysis, a Paradigm of High Technology Medicine.
AB  - In our high-technology, highly polluted world, medicine plays an important role
      balancing saving lives with the expenses of growing amounts of waste products,
      not only biologically dangerous (the potentially "contaminated" or "hazardous"
      waste) but also potentially harmful for the planet (nonrecyclable, plastic
      waste). Dialysis, the prototype of high-technology medicine, is central to these
      problems, as the present treatment of about 2 million patients produces an
      enormous quantity of waste (considering hazardous waste only about 2 kg per
      session, with 160 sessions per year, that is 320 kg per patient, or about 640,000
      tons of hazardous waste per year for 2 million patients, roughly corresponding to
      6 nuclear aircraft carriers). Furthermore, obsolete dialysis machines, and water
      treatments are discharged, adding to the "technological waste." Water produced by
      the reverse osmosis is also discharged; this is the only nonhazardous,
      nonpolluting waste, but in particular in dry areas, wasting water is a great
      ecologic concern. The present review is aimed at discussing strategies already in
      place and to be further implemented for reducing this particular "uremic toxin"
      for the earth: dialysis waste, including dialysis disposables, water, and
      dialysis machines.

PMID- 29056172
TI  - Erratum.

PMID- 29056171
TI  - Happy Holidays.

PMID- 29056173
TI  - Kidney-Friendly Protein Choices.

PMID- 29056174
TI  - Time for Nursing Homes to Recognize and Address Disparities in Care.

PMID- 29056175
TI  - Examining Racial and Ethnic Differences in Nursing Home Quality.
AB  - BACKGROUND: Identifying racial/ethnic differences in quality is central to
      identifying, monitoring, and reducing disparities. Although disparities across
      all individual nursing home residents and disparities associated with between
      nursing home differences have been established, little is known about the degree
      to which quality of care varies by race//ethnicity within nursing homes. A study
      was conducted to measure within-facility differences for a range of publicly
      reported nursing home quality measures. METHODS: Resident assessment data on
      approximately 15,000 nursing homes and approximately 3 million residents (2009)
      were used to assess eight commonly used and publicly reported long-stay quality
      measures: the proportion of residents with weight loss, with high-risk and low
      risk pressure ulcers, with incontinence, with depressive symptoms, in restraints
      daily, and who experienced a urinary tract infection or functional decline. Each
      measure was stratified by resident race/ethnicity (non-Hispanic white, non
      Hispanic black, and Hispanic), and within-facility differences were examined.
      RESULTS: Small but significant differences in care on average were found, often
      in an unexpected direction; in many cases, white residents were experiencing
      poorer outcomes than black and Hispanic residents in the same facility. However,
      a broad range of differences in care by race/ethnicity within nursing homes was
      also found. CONCLUSION: The results suggest that care is delivered equally across
      all racial/ethnic groups in the same nursing home, on average. The results
      support the call for publicly reporting stratified nursing home quality measures
      and suggest that nursing home providers should attempt to identify racial/ethnic
      within-facility differences in care.

PMID- 29056176
TI  - Care Transitions Between Hospitals and Skilled Nursing Facilities: Perspectives
      of Sending and Receiving Providers.
AB  - BACKGROUND: One in four Medicare patients hospitalized for acute medical illness
      is discharged to a skilled nursing facility (SNF); 23% of these patients are
      readmitted to the hospital within 30 days. The care transition from hospital to
      SNF is often marked by disruptions in care and poor communication among hospital
      and SNF providers. A study was conducted to identify the perspectives of sending
      and receiving providers regarding care transitions between the hospital and the
      SNF. METHODS: Hospital (N = 25) and SNF (N = 16) providers participated in
      qualitative interviews assessing patient transfers and experiences with unplanned
      hospital readmissions. Data were analyzed by a multidisciplinary coding team
      using the constant comparison method. RESULTS: Four main themes emerged:
      increasing patient complexity, identifying an optimal care setting, rising
      financial pressure, and barriers to effective communication. The data highlighted
      hospital and SNF providers' shared concerns about patient-level risk factors and
      escalating costs of care. The data also identified issues that separate hospital
      and SNF providers, including different access to resources and information.
      CONCLUSION: Hospital and SNF providers are challenged to meet the needs of
      complex patients. They are asked to establish comprehensive care plans for
      patients with significant medical and psychosocial issues while navigating tense
      relationships between health care institutions and rising financial pressures.
      The concerns of both hospital and SNF providers must be considered in order to
      develop practices that can improve the quality, cost, and safety of care
      transitions.

PMID- 29056177
TI  - Use of Unit-Based Interventions to Improve the Quality of Care for Hospitalized
      Medical Patients: A National Survey.
AB  - BACKGROUND: Recent publications have drawn attention to interventions to redesign
      aspects of care delivery for hospitalized medical patients, including
      localization of physicians to specific units, nurse-physician co-leadership,
      interdisciplinary rounds (IDR), and access to quality performance data. Use of
      these interventions across hospitals has not been previously described. METHODS:
      A cross-sectional survey of internal medicine (IM) residency program directors
      and hospital medicine group (HMG) leaders in the United States was conducted to
      characterize use of unit-based interventions on inpatient medical services. The
      survey served as a pilot study to assess the use of localization of physicians to
      specific units, nurse-physician co-leadership, IDR, and access to quality
      performance data. RESULTS: Ninety-four IM program directors (response rate,
      23.3%) and 62 HMG leaders (response rate, 20.7%) responded. No single
      intervention was used by the vast majority of sites, and the extent and intensity
      of use varied. About a quarter of respondents indicated that physicians typically
      cared for patients on only one to two units, a third or fewer had unit co
      leadership on at least half of hospital units, fewer than half had daily IDR, and
      approximately half had access to unit-level performance data. Most IM programs
      and hospitalist groups had implemented 0 to 1 interventions to a high degree of
      fidelity, and few (<= 5%) had implemented all 4. CONCLUSION: IM program directors
      and HMG leaders reported variation in use of unit-based interventions to improve
      quality of care for medical inpatients. Future research should evaluate the
      association of the degree and intensity of using unit-based interventions on
      patient outcomes.

PMID- 29056178
TI  - Root Cause Analysis of ICU Adverse Events in the Veterans Health Administration.
AB  - BACKGROUND: ICUs' provision of complex care for critically ill patients results
      in an environment with a high potential for adverse events. A study was conducted
      to characterize adverse events in Veterans Health Administration (VHA) ICUs that
      underwent root cause analysis (RCA) and to identify the root causes and their
      recommended actions. METHODS: This retrospective observational study of RCA
      reports concerned events that occurred in VHA ICUs or as a result of ICU
      processes from January 1, 2013, through December 31, 2014. The type of event,
      root causes, and recommended actions were measured. RESULTS: Some 70 eligible
      RCAs were identified in 47 of the 120 facilities with an ICU in the VHA system.
      Delays in care (30.0%) and medication errors (28.6%) were the most common types
      of events. There were 152 root causes and 277 recommended actions. Root causes
      often involved rules, policies, and procedure processes (28.3%), equipment/supply
      issues (15.8%), and knowledge deficits/education (15.1%). Common actions
      recommended were policy, procedure, and process actions (34.4%) and
      training/education actions (31.4%). Of the actions implemented, 84.4% had a
      reported effectiveness of "much better" or "better." CONCLUSION: ICU adverse
      events often had several root causes, with protocols and process-of-care issues
      as root causes regardless of event type. Actions often included standardization
      of processes and training/education. Several recommendations can be made that may
      improve patient safety in the ICU, such as standardization of care process,
      implementation of team training programs, and simulation-based training.

PMID- 29056180
TI  - Using Fault Trees to Advance Understanding of Diagnostic Errors.
AB  - PROBLEM DEFINITION: Diagnostic errors annually affect at least 5% of adults in
      the outpatient setting in the United States. Formal analytic techniques are only
      infrequently used to understand them, in part because of the complexity of
      diagnostic processes and clinical work flows involved. In this article,
      diagnostic errors were modeled using fault tree analysis (FTA), a form of root
      cause analysis that has been successfully used in other high-complexity, high
      risk contexts. How factors contributing to diagnostic errors can be
      systematically modeled by FTA to inform error understanding and error prevention
      is demonstrated. INITIAL APPROACH: A team of three experts reviewed 10 published
      cases of diagnostic error and constructed fault trees. The fault trees were
      modeled according to currently available conceptual frameworks characterizing
      diagnostic error. The 10 trees were then synthesized into a single fault tree to
      identify common contributing factors and pathways leading to diagnostic error.
      KEY INSIGHTS: FTA is a visual, structured, deductive approach that depicts the
      temporal sequence of events and their interactions in a formal logical hierarchy.
      The visual FTA enables easier understanding of causative processes and cognitive
      and system factors, as well as rapid identification of common pathways and
      interactions in a unified fashion. In addition, it enables calculation of
      empirical estimates for causative pathways. Thus, fault trees might provide a
      useful framework for both quantitative and qualitative analysis of diagnostic
      errors. NEXT STEPS: Future directions include establishing validity and
      reliability by modeling a wider range of error cases, conducting quantitative
      evaluations, and undertaking deeper exploration of other FTA capabilities.

PMID- 29056179
TI  - Implementing the Comprehensive Unit-Based Safety Program (CUSP) to Improve
      Patient Safety in an Academic Primary Care Practice.
AB  - BACKGROUND: While there is growing awareness of the risk of harm in ambulatory
      health care, most patient safety efforts have focused on the inpatient setting.
      The Comprehensive Unit-based Safety Program (CUSP) has been an integral part of
      highly successful safety efforts in inpatient settings. In 2014 CUSP was
      implemented in an academic primary care practice. METHODS: As part of CUSP
      implementation, staff and clinicians underwent training on the science of safety
      and completed a two-question safety assessment survey to identify safety concerns
      in the practice. The concerns identified by team members were used to select two
      initial safety priorities. The impact of CUSP on safety climate and teamwork was
      assessed through a pre-post comparison of results on the validated Safety
      Attitudes Questionnaire. RESULTS: Ninety-six percent of staff completed science
      of safety training as part of CUSP implementation, and 100% of staff completed
      the two-question safety assessment. The most frequently identified safety
      concerns were related to medications (n = 11, 28.2), diagnostic testing (n = 9,
      25), and communication (n = 5, 14). The CUSP team initially prioritized
      communication and infection control, which led to standardization of work flows
      within the practice. Six months following CUSP implementation, large but
      nonstatistically significant increases were found for the percentage of survey
      respondents who reported knowledge of the proper channels for questions about
      patient safety, felt encouraged to report safety concerns, and believed that the
      work setting made it easy to learn from the errors of others. CONCLUSION: CUSP is
      a promising tool to improve safety climate and to identify and address safety
      concerns within ambulatory health care.

PMID- 29056181
TI  - A Scalable Program for Customized Patient Education Videos.
AB  - PROBLEM DEFINITION: Patients must make sense of increasingly complex information
      to navigate their health and the health care system, with limited opportunity to
      do so in clinical settings. Patient education videos may help to communicate key
      information, but they are often impersonal and cumbersome to produce or update
      with new evidence. To address these limitations, a program was developed to
      facilitate local video creation to deliver targeted information to patients.
      APPROACH: The Patient Education Video Program was created at a large urban
      academic medical center. The medical director and two project managers worked
      with clinicians and patients to create and disseminate short, single-topic videos
      organized by segments. The videos educated patients on clinical and service
      topics such as self-care for low back pain and postoperative protocols. Videos
      were filmed and modified on a user-friendly mobile device application, then
      prescribed by sharing a link to the online video platform. Video creators were
      engaged through a learning collaborative, a physician incentive program, and a
      residency elective in which trainees designed video-based care redesign projects.
      OUTCOMES: The program was introduced to practice sites across 26 departments.
      Some 269 videos received 19,713 unique views in a two-year period. In an
      operational survey, 1,034 (86.0%) of 1,203 viewer responses stated that a video
      helped them understand their health, medical condition, or treatment plan. KEY
      INSIGHTS: A program to facilitate video creation and dissemination is feasible.
      Clinicians were most receptive to creating and using videos that addressed direct
      clinical or operational needs.

PMID- 29056182
TI  - A Novel Process Audit for Standardized Perioperative Handoff Protocols.
AB  - A perioperative handoff protocol provides a standardized delivery of
      communication during a handoff that occurs from the operating room to the
      postanestheisa care unit or ICU. The protocol's success is dependent, in part, on
      its continued proper use over time. A novel process audit was developed to help
      ensure that a perioperative handoff protocol is used accurately and appropriately
      over time. The Audit Observation Form is used for the Audit Phase of the process
      audit, while the Audit Averages Form is used for the Data Analysis Phase.
      Employing minimal resources and using quantitative methods, the process audit
      provides the necessary means to evaluate the proper execution of any
      perioperative handoff protocol.

PMID- 29056183
TI  - Baking soda dentifrices and oral health.

PMID- 29056184
TI  - Evidence for biofilm acid neutralization by baking soda.
AB  - BACKGROUND: The generating of acids from the microbial metabolism of dietary
      sugars and the subsequent decrease in biofilm pH below the pH at which tooth
      mineral begins to demineralize (critical pH) are the key elements of the dental
      caries process. Caries preventive strategies that rapidly neutralize biofilm
      acids can prevent demineralization and favor remineralization and may help
      prevent the development of sugar-induced dysbiosis that shifts the biofilm toward
      increased cariogenic potential. Although the neutralizing ability of sodium
      bicarbonate (baking soda) has been known for many years, its anticaries potential
      as an additive to fluoride dentifrice has received only limited investigation.
      TYPES OF STUDIES REVIEWED: There is evidence that baking soda rapidly can reverse
      the biofilm pH decrease after a sugar challenge; however, the timing of when it
      is used in relation to a dietary sugar exposure is critical in that the sooner
      its used the greater the benefit in preventing a sustained biofilm pH decrease
      and subsequent demineralization. Furthermore, the effectiveness of baking soda in
      elevating biofilm pH appears to depend on concentration. Thus, the concentration
      of baking soda in marketed dentifrice products, which ranges from 10% to 65%, may
      affect their biofilm pH neutralizing performance. People with hyposalivation
      particularly may benefit from using fluoride dentifrice containing baking soda
      because of their diminished ability to clear dietary sugars and buffer biofilm
      acids. CONCLUSIONS: Although promising, there is the need for more evidence that
      strategies that modify the oral ecology, such as baking soda, can alter the
      cariogenic (acidogenic and aciduric) properties of biofilm microorganisms.
      PRACTICAL IMPLICATIONS: The acid neutralization of dental biofilm by using
      fluoride dentifrice that contains baking soda has potential for helping
      counteract modern high-sugar diets by rapidly neutralizing biofilm-generated
      acid, especially in people with hyposalivation.

PMID- 29056185
TI  - Baking soda dentifrice and periodontal health: A review of the literature.
AB  - BACKGROUND: Mechanical disruption of dental biofilm is critical to maintain
      periodontal health. Baking soda-containing dentifrices have shown to be potential
      aids for improving gingival health and maintaining dental biofilm control. TYPES
      OF STUDIES REVIEWED: Evidence from classic and contemporary literature is
      reviewed and summarized in this review. In vitro and in vivo (animal and human,
      respectively) studies and clinical trials have been analyzed. CONCLUSIONS: Some
      clinical studies demonstrated the benefits of baking soda dentifrices in plaque
      and gingivitis reduction. Clinical trials with longer follow-up would be useful
      to confirm the impact of baking soda on gingival health. PRACTICAL IMPLICATIONS:
      Regular dental biofilm control and adjunctive use of baking soda dentifrices in
      an otherwise healthy and compliant patient may provide success in maintenance of
      gingival health.

PMID- 29056186
TI  - Stain removal and whitening by baking soda dentifrice: A review of literature.
AB  - BACKGROUND: Tooth discoloration may be caused by intrinsic or extrinsic stains or
      a combination of both. There are 2 major approaches to removing the stains,
      including the chemical mechanism using peroxides for tooth bleaching and the
      mechanical mechanism using abrasives in prophylactic pastes and dentifrices to
      remove stains, resulting in a whitening effect. Attempts have also been made to
      add a low concentration of peroxides to dentifrices to enhance their abrasive
      cleaning to remove tooth stains. TYPES OF STUDIES REVIEWED: This article provides
      a review of both in vitro and clinical studies on stain removal and whitening
      effect of dentifrices containing sodium bicarbonate (baking soda). In recent
      years, whitening dentifrices have become popular because of little additional
      effort for use, ease of availability, low cost, and accumulated evidence of
      clinical efficacy and safety in the literature. Advances in research and
      technology have led to innovative formulations of dentifrices using baking soda
      as the sole abrasive or a component of an abrasive system. Baking soda is
      biologically compatible with acid-buffering capacities, antibacterial at high
      concentrations, and has a relatively lower abrasivity. CONCLUSIONS: The evidence
      available in the literature indicates that baking soda-based dentifrices are
      effective and safe for tooth stain removal and consequently whitening. A number
      of clinical studies have also shown that baking soda-based dentifrices are more
      effective in stain removal and whitening than some non-baking soda-containing
      dentifrices with a higher abrasivity. So far, research efforts have mainly
      focused on stain removal and tooth-whitening efficacy and clinical safety of
      baking soda dentifrices used with manual toothbrushes, with only a few studies
      investigating their effects using powered toothbrushes, for which further
      research is encouraged. PRACTICAL IMPLICATIONS: As part of a daily oral hygiene
      practice, baking soda-based dentifrice is a desirable, alternative or additional
      measure for tooth stain removal and whitening.

PMID- 29056187
TI  - Baking soda as an abrasive in toothpastes: Mechanism of action and safety and
      effectiveness considerations.
AB  - BACKGROUND: Toothpastes can be formulated with different abrasive systems,
      depending on their intended clinical application. This formulation potentially
      affects their effectiveness and safety and, therefore, requires proper
      understanding. In this article, the authors focused on abrasive aspects of
      toothpastes containing sodium bicarbonate (baking soda), which have gained
      considerable attention because of their low abrasivity and good compatibility,
      while providing clinical effectiveness (further detailed in the other articles of
      this special issue). The authors first appraised the role of toothpaste
      abrasivity on tooth wear, exploring some underlying processes and the existing
      methods to determine toothpaste abrasivity. TYPES OF STUDIES REVIEWED: The
      authors reviewed the available data on the abrasivity of toothpastes containing
      baking soda and reported a summary of findings highlighting the clinical
      implications. CONCLUSIONS: On the basis of the collected evidence, baking soda
      has an intrinsic low-abrasive nature because of its comparatively lower hardness
      in relation to enamel and dentin. Baking soda toothpastes also may contain other
      ingredients, which can increase their stain removal effectiveness and,
      consequently, abrasivity. PRACTICAL IMPLICATIONS: Even those formulations have
      abrasivity well within the safety limit regulatory agencies have established and,
      therefore, can be considered safe.

PMID- 29056188
TI  - Effect of baking soda in dentifrices on plaque removal.
AB  - BACKGROUND: The prevention of dental caries and periodontal diseases targets
      control of dental plaque biofilm. In this context, chemical agents could
      represent a valuable complement to mechanical plaque control by reducing and
      controlling biofilm formation. METHODS: The literature on the effectiveness of
      different dentifrices has not, however, been carefully categorized. A lack of
      consensus exists among dental professionals on a recommendation for a universal
      dentifrice for plaque control. The authors reviewed the scientific data on the
      different properties of sodium bicarbonate (baking soda)-containing dentifrices
      and their effectiveness in plaque removal. RESULTS: The results of the literature
      search show that baking soda-containing dentifrices are ideal candidates to be
      considered as a universal dentifrice because baking soda is inexpensive, abundant
      in supply, highly biocompatible, exhibits specific antibacterial properties to
      oral microorganisms, has low abrasivity, and is effective in plaque biofilm
      removal. CONCLUSIONS: Although some patients may benefit from desensitizing or
      high fluoride-containing dentifrices, those with routine needs may find using
      dentifrices containing baking soda and fluoride effective. PRACTICAL
      IMPLICATIONS: Baking soda and fluoride dentifrices, therefore, may perhaps be
      considered as a criterion standard for patients with routine oral hygiene needs.

PMID- 29056189
TI  - Evaluating the Costs of IR in Health Care Delivery: Proceedings from a Society of
      Interventional Radiology Research Consensus Panel.

PMID- 29056190
TI  - Positron Emission Tomography/CT to Localize Radioactivity in a Radioembolization
      Delivery System.

PMID- 29056191
TI  - Percutaneous Transparaumbilical Embolization of Spontaneous Portosystemic Shunts
      for the Treatment of Hepatic Encephalopathy.
AB  - The medical records of 7 patients who underwent percutaneous transparaumbilical
      embolization of spontaneous portosystemic shunts for treatment of hepatic
      encephalopathy (HE) were retrospectively reviewed. Technical success was achieved
      in 100% (7/7) of patients. Four patients had complete resolution and 3 had
      improvement of signs and symptoms of HE within 3 days after the procedure for a
      clinical success rate of 100% (7/7). New-onset esophageal varices, a major
      complication, occurred in 1 patient. No other major complications were
      encountered. HE recurred in 71.4% (5/7) of patients during a median follow-up
      period of 43 months (range, 4-111 months).

PMID- 29056192
TI  - Undivided Common Iliac Artery: Unclear Embryology.

PMID- 29056193
TI  - Laser-Assisted Transgraft Embolization: A Technique for the Treatment of Type II
      Endoleaks.
AB  - A transgraft embolization (TGE) technique was performed in a patient to treat a
      type II endoleak. Using a transfemoral arterial approach, the endograft was
      punctured using a coronary laser catheter aimed toward the type II endoleak
      nidus, which was treated with Onyx (Medtronic, Minneapolis, Minnesota). TGE
      resulted in successful embolization, as demonstrated on 1-year follow-up CT
      angiography, which showed complete elimination of the type II endoleak and
      shrinkage of the aneurysmal sac. TGE is an alternative to transarterial
      embolization, translumbar embolization, and transcaval embolization.

PMID- 29056194
TI  - Comparative Outcomes of Mechanical Thrombectomy for Acute Ischemic Stroke in
      Patients with and without Atrial Fibrillation.

PMID- 29056195
TI  - Omental Infarction after Transarterial Chemoembolization due to Nontarget
      Embolization of an Extrahepatic Branch from the Right Hepatic Artery.

PMID- 29056196
TI  - Retrograde Endovascular Stenting of Preocclusive Celiac Artery Stenosis with Loop
      Technique Associated with Pancreaticoduodenal Artery Aneurysm Embolization.

PMID- 29056197
TI  - Pharmacomechanical Thrombectomy of Superficial Venous Thrombosis in Sturge-Weber
      and Klippel-Trenaunay Overlap Syndrome.

PMID- 29056198
TI  - Spontaneous Bladder Stone Voiding after Prostatic Artery Embolization.

PMID- 29056199
TI  - A 5-Dollar Nephrostomy Training Phantom Using Common Household and Hospital
      Supplies.

PMID- 29056200
TI  - Lessons From Team Nursing.

PMID- 29056202
TI  - States' Progress Toward Nurse Practitioner Full Practice Authority: Contemporary
      Challenges and Strategies.

PMID- 29056201
TI  - Pediatric Hip Pain: A Case Study.
AB  - Hip pain in children can present a diagnostic challenge for the pediatric primary
      care provider. This case study examines an otherwise healthy 3-year-old girl with
      unilateral hip pain and intermittent refusal to bear weight on the affected side.
      Through history and physical examination, the provider was able to appropriately
      diagnose transient synovitis. This case study will summarize the care for hip
      pain in a child, including potential causes, a focused history and physical
      examination, appropriate diagnostic testing, and recommendations for home care
      and follow-up.

PMID- 29056203
TI  - Woman With Swelling of the Left Breast.

PMID- 29056205
TI  - The Secret Life of Policies.

PMID- 29056204
TI  - Adolescent Male With Abdominal Pain.

PMID- 29056207
TI  - Of Sugar and Stab Wounds.

PMID- 29056206
TI  - Clinical Policy: Emergency Department Management of Patients Needing Reperfusion
      Therapy for Acute ST-Segment Elevation Myocardial Infarction.

PMID- 29056208
TI  - I'll Fly Away.

PMID- 29056209
TI  - Robert L. Wears, MD, PhD, 1947-2017.

PMID- 29056210
TI  - Medicaid and Moral Hazard: Covering Emergency Department Visits Increases
      Emergency Department Visits...or Not?: November 2017 Annals of Emergency Medicine
      Journal Club.

PMID- 29056211
TI  - Newborn With a Rash.

PMID- 29056212
TI  - Woman With Headache and Neck Swelling.

PMID- 29056213
TI  - You Traveled the World and All You Got Was Ascariasis.

PMID- 29056214
TI  - Treatment Goal for Agitation: Sedation or Calming.

PMID- 29056215
TI  - In reply.

PMID- 29056216
TI  - Prognostic Assessment of Febrile Neutropenia in the Emergency Department.

PMID- 29056217
TI  - In reply.

PMID- 29056218
TI  - Elderly Woman With Chest Pain and Cough.

PMID- 29056219
TI  - Man With Blunt Abdominal Trauma.

PMID- 29056220
TI  - Child With a Serpinginous Structure in the Bowel.

PMID- 29056221
TI  - Editor's perspectives - October 2017.

PMID- 29056222
TI  - Corrigendum to "The effect of vitamin D supplementation on knee osteoarthritis: A
      meta-analysis of randomized controlled trials" [Int. J. Surg. 46 (2017) 14-20].

PMID- 29056223
TI  - Losing Sleep Over Your Health.

PMID- 29056225
TI  - Discussion of: "Post-operative delirium is associated with increased 5-year
      mortality".

PMID- 29056227
TI  - Intravenous regional anaesthesia (Bier's block) for pediatric forearm fractures
      in a pediatric emergency department-Experience from 2003 to 2014.
AB  - STUDY OBJECTIVES: To evaluate the efficacy (length of stay in the emergency
      department and failure rate of Bier's block) and safety profile (death and major
      complications) of Bier's block in its use for manipulation and reduction of
      paediatric forearm fractures. METHODS: This is a retrospective cohort study of
      pediatric patients in KKWomen's and Children's Hospital Children's Emergency
      Department with forearm fractures between Jan 2003 and Dec 2014 who underwent
      manipulation and reduction using Bier's block. Demographic data, time from
      registration to discharge, major complications and success rate were collated in
      a standardized data collection form. A subanalysis of the Bier's block group from
      2009 to 2014 was performed and compared to a corresponding data set of paediatric
      patients who underwent manipulation and reduction of forearm fractures using
      ketamine for procedural sedation from 2009 to 2014. RESULTS: 1781 cases of
      paediatric forearm fractures were analysed. The mean age of patients in the
      Bier's block group was 12.0 years (range 5.5-17.8 years old). Of all patients
      undergoing Bier's block, 1471 out of 1781 patients were male (82.7%). The mean
      length of stay (LOS) in the department was 168+/-72min, measured from time of
      registration till departure. From our subanalysis of data from 2009 to 2014, the
      mean LOS for the Bier's block group was shorter - 170min compared to 238min for
      the ketamine group (P <0.0001). 2 patients had failed Bier's block which required
      a repeat procedural sedation using ketamine. 96% of patients who underwent Bier's
      block were discharged with an outpatient orthopaedic appointment. There were no
      deaths or major complications identified in our study. CONCLUSION: Bier's block
      is a safe technique for reduction of fractures when used in the appropriate
      population and fracture types, with a low failure rate and no major complications
      including death. Compared to the ketamine group, it has a shorter length of stay
      in the emergency department. We recommend the adoption of this practice for
      manipulation and reduction of pediatric forearm fractures in the Emergency
      Department with a formalised protocol to reduce and prevent any human errors that
      can potentially result in complications.

PMID- 29056228
TI  - Comparison of Clinical Characteristics, Complications, and Outcomes in Recipients
      Having Heart Transplants <65 Years of Age Versus >=65 Years of Age.
AB  - Advanced recipient age remains a limiting factor for heart transplant candidacy,
      with many centers reluctant to transplant older patients. Here, we report our
      experience with recipients aged >=65 years compared with younger recipients in
      terms of baseline characteristics, intraoperative and immediate postoperative
      experiences, and post-transplant morbidity and survival. The main study outcome
      was primary graft dysfunction (PGD), which has not been widely studied in this
      population. Donor and recipient data from 255 heart transplantations performed
      between 2012 and 2016 were reviewed. Seventy (27%) recipients were >=65 years and
      185 were younger. The older group had a higher frequency of ischemic
      cardiomyopathy and more frequently had a previous sternotomy than the younger
      recipients (all p <0.007). We found no significant differences in post-transplant
      morbidity (intensive care unit and hospital stay, pneumonia, infections,
      reoperation for bleeding, stroke, renal failure, or in-hospital mortality; all p
      >0.12). One-year survival was also similar in the 2 groups (p = 0.88). The
      incidence of moderate or severe PGD was lower in the older group (6%) than in the
      younger group (16%; p = 0.037). Multivariate logistic regression found
      pretransplant creatinine and donor undersizing by predicted heart mass to be
      predictors of moderate to severe PGD, whereas recipient age >=65 years was
      identified as protective against PGD in this cohort. In conclusion, our study
      showed comparable survival and outcomes in recipients >=65 years of age with
      otherwise similar nutritional status and body mass composition.

PMID- 29056229
TI  - Frequency of Coronary Endarterectomy in Patients Undergoing Coronary Artery
      Bypass Grafting at a Single Tertiary Texas Hospital 2010 to 2016 With Morphologic
      Studies of the Operatively Excised Specimens.
AB  - This study examines the frequency of coronary endarterectomy (CE) procedures
      during coronary artery bypass grafting (CABG), and determines the quantity of
      plaque in the specimens. Of the 2,268 CABG operations performed from January 2010
      to June 2016, 35 patients had CE during CABG. The specimens were incised into 5
      mm cross sections, stained by the Movat method, and examined. The number of CEs
      performed ranged from 0.21% to 4.01%. A total of 140 cm of specimens were
      examined, and all 140 cm contained considerable quantities of atherosclerotic
      plaque and narrowed lumens. The quantity of plaque present was similar to or
      greater than that observed in previously studied patients with fatal coronary
      artery disease. The frequency of CE during CABG varies greatly in surgeons. The
      quantity of plaque is enormous, and the lumens are severely narrowed.

PMID- 29056226
TI  - A Dementia-Associated Risk Variant near TMEM106B Alters Chromatin Architecture
      and Gene Expression.
AB  - Neurodegenerative diseases pose an extraordinary threat to the world's aging
      population, yet no disease-modifying therapies are available. Although genome
      wide association studies (GWASs) have identified hundreds of risk loci for
      neurodegeneration, the mechanisms by which these loci influence disease risk are
      largely unknown. Here, we investigated the association between common genetic
      variants at the 7p21 locus and risk of the neurodegenerative disease
      frontotemporal lobar degeneration. We showed that variants associated with
      disease risk correlate with increased expression of the 7p21 gene TMEM106B and no
      other genes; co-localization analyses implicated a common causal variant
      underlying both association with disease and association with TMEM106B expression
      in lymphoblastoid cell lines and human brain. Furthermore, increases in the
      amount of TMEM106B resulted in increases in abnormal lysosomal phenotypes and
      cell toxicity in both immortalized cell lines and neurons. We then combined fine
      mapping, bioinformatics, and bench-based approaches to functionally characterize
      all candidate causal variants at this locus. This approach identified a noncoding
      variant, rs1990620, that differentially recruits CTCF in lymphoblastoid cell
      lines and human brain to influence CTCF-mediated long-range chromatin-looping
      interactions between multiple cis-regulatory elements, including the TMEM106B
      promoter. Our findings thus provide an in-depth analysis of the 7p21 locus linked
      by GWASs to frontotemporal lobar degeneration, nominating a causal variant and
      causal mechanism for allele-specific expression and disease association at this
      locus. Finally, we show that genetic variants associated with risk of
      neurodegenerative diseases beyond frontotemporal lobar degeneration are enriched
      in CTCF-binding sites found in brain-relevant tissues, implicating CTCF-mediated
      gene regulation in risk of neurodegeneration more generally.

PMID- 29056230
TI  - Correlation between gamma-glutamyl transpeptidase activity and outcomes after
      Kasai portoenterostomy for biliary atresia.
AB  - BACKGROUND/PURPOSE: The role of serum gamma-glutamyl transpeptidase (GGT) levels
      in predicting clinical outcomes after Kasai portoenterostomy (KPE) is unknown.
      This study analyzed whether postoperative GGT along with the aspartate
      aminotransferase-to-platelet ratio index (APRi) predicted prognosis of biliary
      atresia (BA). METHODS: Data were retrospectively reviewed for 169 BA patients
      categorized into jaundice-free (JF) (total bilirubin <2.0 mg/dL <=6 months post
      KPE) and persistent jaundice (PJ) groups (total bilirubin >=2.0 mg/dL <=6 months
      post-KPE). Serum biochemical markers, including GGT levels, were measured monthly
      after KPE, and mean GGT levels and APRi were compared between groups. Factors
      predicting native liver survival (NLS) were determined using a Cox regression
      analysis. RESULTS: GGT concentrations >550 IU/L at month 5 (hazard ratio: 1.74, P
      < 0.05), an APRi >0.605 at month 4 (hazard ratio: 3.78, P = 0.001), and being
      jaundice-free at 6 months (hazard ratio: 5.49, P < 0.001) were independent risk
      factors for decreased NLS. CONCLUSIONS: Serum GGT concentrations >550 IU/L at
      month 5 and an APRi >0.605 at month 4 post-KPE were associated with significantly
      lower NLS rates. Among JF patients, those with GGT concentrations >550 IU/L at
      month 5 and APRi >0.605 at month 4 showed poorer outcomes. TYPE OF STUDY:
      Retrospective comparative study LEVEL OF EVIDENCE: Level III.

PMID- 29056232
TI  - Polyoxyethylene alkyl ether carboxylic acids: An overview of a neglected class of
      surfactants with multiresponsive properties.
AB  - In this work, an overview on aqueous solutions of polyoxyethylene alkyl ether
      carboxylic acids is given. Unique properties arise from the combination of the
      nonionic, temperature-responsive polyoxyethylene block with the weakly ionic, pH
      responsive carboxylic acid termination in a single surfactant headgroup.
      Accordingly, this class of surfactant finds broad application across very
      different sectors. Despite their large use on an industrial and a technical
      scale, the literature lacks a systematic and detailed characterization of their
      physico-chemical properties which is provided herein. In addition, a
      comprehensive overview is given of their self-assembly and interfacial behavior,
      of their use as colloidal building blocks and for large-scale applications.

PMID- 29056233
TI  - Angiotensin-(1-7) prevents atrial tachycardia induced-heat shock protein 27
      expression.
AB  - OBJECTIVE: We aimed to investigate the effects of angiotensin-(1-7) [Ang-(1-7)]
      on heat-shock protein 27 (HSP27) in a canine model of induced tachycardia.
      METHODS: Eighteen dogs were randomized into three equal treatment groups: sham,
      pacing and pacing+Ang-(1-7) group. The dogs in the last two groups were subjected
      to 2weeks of rapid atrial pacing (500bpm). The effects of Ang-(1-7) on HSP27 were
      assessed by real-time polymerase chain reaction and western blot. RESULTS: The
      expression levels of atrial HSP27 mRNA and protein were significantly (P<0.05)
      higher for the pacing group than the sham group and significantly (P<0.05) lower
      for the pacing+Ang-(1-7) group than the pacing group. There was no significant
      difference between the HSP27 expression levels in the right and left atria among
      all three groups. CONCLUSIONS: Our findings suggest that the overexpression of
      HSP27 may possibly be occurring as an adaptive response that allows atrial
      tissues to cope with rapid atrial pacing, and an inhibiting effect of Ang-(1-7)
      on atrial remodeling may be one of the mechanisms responsible for the attenuation
      of HSP27 up-regulation induced by rapid pacing.

PMID- 29056231
TI  - Mitochondrial ADP/ATP Carrier in Dodecylphosphocholine Binds Cardiolipins with
      Non-native Affinity.
AB  - Biophysical investigation of membrane proteins generally requires their
      extraction from native sources using detergents, a step that can lead, possibly
      irreversibly, to protein denaturation. The propensity of dodecylphosphocholine
      (DPC), a detergent widely utilized in NMR studies of membrane proteins, to
      distort their structure has been the subject of much controversy. It has been
      recently proposed that the binding specificity of the yeast mitochondrial ADP/ATP
      carrier (yAAC3) toward cardiolipins is preserved in DPC, thereby suggesting that
      DPC is a suitable environment in which to study membrane proteins. In this
      communication, we used all-atom molecular dynamics simulations to investigate the
      specific binding of cardiolipins to yAAC3. Our data demonstrate that the
      interaction interface observed in a native-like environment differs markedly from
      that inferred from an NMR investigation in DPC, implying that in this detergent,
      the protein structure is distorted. We further investigated yAAC3 solubilized in
      DPC and in the milder dodecylmaltoside with thermal-shift assays. The loss of
      thermal transition observed in DPC confirms that the protein is no longer
      properly folded in this environment.

PMID- 29056234
TI  - Benign paroxysmal positional vertigo: Diagnostic criteria Consensus document of
      the Committee for the Classification of Vestibular Disorders of the Barany
      Society.
AB  - This article presents operational diagnostic criteria for benign paroxysmal
      positional vertigo (BPPV), formulated by the Committee for Classification of
      Vestibular Disorders of the Barany Society. The classification reflects current
      knowledge of clinical aspects and pathomechanisms of BPPV and includes both
      established and emerging syndromes of BPPV. It is anticipated that growing
      understanding of the disease will lead to further development of this
      classification.

PMID- 29056235
TI  - Maternal effector T cells within decidua: The adaptive immune response to
      pregnancy?
AB  - In human pregnancy the maternal immune system plays a critical role in the
      regulation of many aspects of human reproduction including implantation,
      placentation and defence against infection. Interest has been focussed on the
      role of uterine natural killer cells (uNK) in the maternal decidua whereas
      effector CD4+ and CD8+ T cells have received much less attention despite the
      observation that they represent a major proportion of decidual leucocytes in the
      latter phase of pregnancy. A range of recent studies have demonstrated that human
      decidual T cells are highly differentiated, express a range of cytokines and
      cytotoxic markers, and demonstrate a unique transcriptional profile characterized
      by high level expression of genes involved in interferon-signalling. Moreover,
      subpopulations of effector T cells demonstrate specificity for fetal tissue and
      are regulated through expression of inhibitory checkpoint proteins and T
      regulatory cells. Nevertheless, many questions remain to be answered, such as the
      potential role of maternal effector T cells in either supporting successful
      pregnancy or potentially clearing fetal cells that have entered the maternal
      circulation. In addition, there is an increasing interest in the role of maternal
      effector T cells in the pathogenesis of disorders such as chronic villitis
      miscarriage, stillbirth, fetal growth restriction and pre-eclampsia. Current
      debates in relation to these questions will be discussed within this review.

PMID- 29056236
TI  - The superiorly based bilobed flap for nasal reconstruction.
AB  - BACKGROUND: The laterally based bilobed flap is commonly used for the
      reconstruction of small- to medium-sized defects of the distal portion of the
      nose; However, when this flap is used to repair defects that are larger, more
      cephalic, or more lateral on the nose, there is a risk for lower nasal
      distortion. Reorienting the base superiorly preserves the advantages of the
      traditional design while minimizing this risk. OBJECTIVE: To demonstrate the
      design, execution, and efficacy of the superiorly based bilobed flap. METHODS: A
      retrospective review examined all superiorly based bilobed flaps performed by 1
      surgeon (J.C.) in 2000-2016 after tumor extirpation by Mohs micrographic surgery
      at a single institution. RESULTS: A total of 41 surgical defects were closed with
      40 flaps between June 2000 and August 2016 (1 patient had 2 defects closed with a
      single flap). Of the tumors, 55% were located on the nasal dorsum, and the median
      of the longest postoperative tumor axis was 1.4 cm. Follow-up was available for
      40 flaps, and no infections, hematomas, or episodes of full-thickness necrosis
      were observed. LIMITATIONS: Data were collected retrospectively from a single
      institution without a standardized assessment tool for aesthetic outcomes.
      CONCLUSION: The superiorly based bilobed flap is useful for nasal reconstruction.

PMID- 29056237
TI  - Hidradenitis suppurativa and diabetes mellitus: A systematic review and meta
      analysis.
AB  - BACKGROUND: The relationship between hidradenitis suppurativa and diabetes
      mellitus is not well understood. OBJECTIVE: To compare the prevalence of diabetes
      mellitus between patients with and without hidradenitis suppurativa. METHODS: We
      conducted a systematic review and meta-analysis, which included primary
      observational studies that reported the prevalence of diabetes mellitus among
      patients with hidradenitis suppurativa in the PubMed, Embase, Cochrane Library,
      LILACS, and Scielo databases from 1947 to June 13, 2017. A random effects model
      for pooled odds ratio was used for data analysis. Publication bias was assessed
      by funnel plot and the Egger test. RESULTS: The systematic review included
      107,050 patients from 14 studies; the meta-analysis included 104,373 patients
      from 7 studies. On the basis of meta-analysis, the prevalence of diabetes
      mellitus was 10.6% in patients with hidradenitis suppurativa and 3.8% in patients
      without hidradenitis suppurativa. Compared with the general population, patients
      with hidradenitis suppurativa were nearly 3 times more likely to have diabetes
      mellitus (pooled odds ratio, 2.78; 95% confidence interval, 1.79-4.31).
      LIMITATIONS: We were restricted by the quantity and quality of available data.
      CONCLUSION: Hidradenitis suppurativa is significantly associated with an
      increased prevalence of diabetes mellitus.

PMID- 29056238
TI  - Value of routine investigations to predict loop diuretic down-titration success
      in stable heart failure.
AB  - AIMS: Guidelines advocate down-titration of loop diuretics in chronic heart
      failure (CHF) when patients have no signs of volume overload. Limited data are
      available on the expected success rate of this practice or how routine diagnostic
      tests might help steering this process. METHODS AND RESULTS: Fifty ambulatory CHF
      patients on stable neurohumoral blocker/diuretic therapy for at least 3months
      without any clinical sign of volume overload were prospectively included to
      undergo loop diuretic down-titration. All patients underwent a similar pre-down
      titration evaluation consisting of a dyspnea scoring, physical examination,
      transthoracic echocardiography (diastolic function, right ventricular function,
      cardiac filling pressures and valvular disease), blood sample (serum creatinine,
      plasma NT-pro-BNP and neurohormones). Loop diuretic maintenance dose was
      subsequently reduced by 50% or stopped if dose was <=40mg furosemide equivalents.
      Successful down-titration was defined as a persistent dose reduction after 30days
      without weight increase >1.5kg or new-onset symptoms of worsening heart failure.
      At 30-day follow-up, down-titration was successful in 62% (n=31). In 12/19
      patients exhibiting down-titration failure, this occurred within the first week.
      Physical examination, transthoracic echocardiography and laboratory analysis had
      limited predictive capability to detect patients with down-titration
      success/failure (positive likelihood-ratios below 1.5, or area under the curve
      [AUC] non-statically different from AUC=0.5). CONCLUSION: Loop diuretic down
      titration is feasible in a majority of stable CHF patients in which the treating
      clinician felt continuation of loops was unnecessary to sustain euvolemia.
      Importantly, routine diagnostics which suggest euvolemia, have limited diagnostic
      impact on the post-test probability.

PMID- 29056239
TI  - Short-term exposure to air pollutants increases the risk of ST elevation
      myocardial infarction and of infarct-related ventricular arrhythmias and
      mortality.
AB  - BACKGROUND: The relation between STEMI and air pollution (AP) is scant. We aimed
      to investigate the short term association between AP and the incidence of STEMI,
      and STEMI-related ventricular arrhythmias (VA) and mortality. METHODS: The study
      was carried out in the area of Barcelona from January 2010 to December 2011.
      Daily STEMI rates and incidence of STEMI-related VA and mortality were obtained
      prospectively. The corresponding daily levels of the main pollutants were
      recorded as well as the atmospheric variables. Three cohorts were defined in
      order to minimize exposure bias. The magnitude of association was estimated using
      a time-series design and was adjusted according to atmospheric variables.
      RESULTS: The daily rate of hospital admissions for STEMI was associated with
      increases in PM 2.5, PM 10, lead and NO2 concentrations. VA incidence and
      mortality were associated with increases in PM 2.5 and PM 10 concentrations. In
      the most specific cohort, BCN (Barcelona) Attended & Resident, STEMI incidence
      was associated with increases in PM 2.5 (1.009% per 10MUg/m3) and PM 10
      concentrations (1.005% per 10MUg/m3). VA was associated with increases in PM 2.5
      (1.021%) and PM 10 (1.015%) and mortality was associated with increases in PM 2.5
      (1.083%) and PM 10 (1.045%). CONCLUSIONS: Short-term exposure to high levels of
      PM 2.5 and PM 10 is associated with increased daily STEMI admissions and STEMI
      related VA and mortality. Exposure to high levels of lead and NO2 is associated
      with increased daily STEMI admissions, and NO2 with higher mortality in STEMI
      patients.

PMID- 29056240
TI  - Evaluation of minimum volume standards for surgery in the Netherlands (2003
      2017): A successful policy?
AB  - PURPOSE: To evaluate the introduction and implications of minimum volume
      standards for surgery in Dutch health care from 2003 to 2017 and formulate policy
      lessons for other countries. SETTING: Dutch health care. PRINCIPAL FINDINGS:
      Three eras were identified, representing a trust-and-control cycle in keeping
      with changing roles of different stakeholders in Dutch context. In the first era
      'regulated trust' (2003-2009), the Dutch Inspectorate introduced national volume
      criteria and relied on yearly hospital reported data for information on
      compliance. In the second era 'contract and control' (2009-2017), the effects of
      market-oriented reform became more evident. The Dutch government intervened in
      the market and health insurers introduced selective contracting. Medical
      professionals were prompted to reclaim the initiative. In the current era (2017
      ), a return of trust in self-regulation seems visible. The number of low-volume
      hospitals performing complex surgeries in the Netherlands has decreased and
      research has shown improved outcomes as a result. CONCLUSIONS: Based on the Dutch
      experience, the following lessons can be useful for other health care systems: 1.
      professionals should be in the lead in the development of national quality
      standards, 2. external pressure can be helpful for professionals to take the
      initiative and 3. volume remains a controversial quality measure. Future research
      and policies should focus on the underlying mechanism of volume-outcome
      relationships and overall effects of volume-based policies.

PMID- 29056241
TI  - Corrigendum to "Association between joint stiffness and health-related quality of
      life in community-dwelling older adults" [Arch. Gerontol. Geriatr. 73 (November
      2017) 234-239].

PMID- 29056242
TI  - Exploring falls prevention capabilities, barriers and training needs among
      patient sitters in a hospital setting: A pilot survey.
AB  - Older patients in hospitals are at high risk of falls. Patient sitters are
      sometimes employed to directly observe patients to reduce their risk of falling
      although there is scant evidence that this reduces falls. The primary aim of this
      pilot survey (n = 31) was to explore the patient sitters' falls prevention
      capability, self-efficacy and the barriers and enablers they perceived influenced
      their ability to care for patients during their shifts. Feedback was also sought
      regarding training needs. Most (90%) participants felt confident in their role.
      The most frequent reasons for falls identified were patient-related (n = 91,
      64%), but the most frequent responses identifying preventive strategies were
      environment-related (n = 54, 64%), suggesting that the sitters' capability was
      limited. The main barriers identified to keeping patients safe from falling were
      patient-related (n = 36, 62%) such as cognitive impairment. However,
      opportunities that would enable sitters to do their work properly were most
      frequently categorized as being staff-related (n = 20, 83%), suggesting that the
      sitters have limited ability to address these barriers encountered. While 74% of
      sitters reported they had received previous training, 84% of participants would
      like further training. Patient sitters need more training, and work practice
      needs to be standardized prior to future research into sitter use for falls
      prevention.

PMID- 29056243
TI  - Prognostic significance of standardized uptake value on F18-FDG PET/CT in
      patients with extranodal nasal type NK/T cell lymphoma: A multicenter,
      retrospective analysis.
AB  - OBJECTIVES: The purpose of this study was to evaluate the value of parameters
      assessed with F18-flurodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) in predicting relapse free survival and overall survival in
      patients with extranodal nasal type NK/T cell lymphoma. METHODS: Thirty-six
      patients with extranodal nasal type NK/T cell lymphoma, and who underwent PET/CT
      prior to curative treatment, were enrolled at five institutions. Volumes of
      interest covering the entire tumor volume were delineated on PET/CT images, and
      the maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic
      tumor volume (MTV), and total lesion glycolysis (TLG) were measured using
      thresholds of 40% of SUVmax. Furthermore, we compared the difference in F18-FDG
      avidity according to Epstein-Barr virus (EBV) infection status. RESULTS: The
      SUVmax (p=0.041) and SUVmean (p=0.049) in patients who died were higher than the
      respective values of those who survived. A higher TLG (>45.8) was associated with
      relapse free survival (HR 7.856, p=0.034). Ann Arbor stage (III-IV, HR 14.12,
      p=0.004), and a higher SUVmax (>12.6, p=0.024) and SUVmean (>6.4, p=0.024) were
      associated with poor survival. However, neither the MTV nor the TLG (volumetric
      parameters) were significant predictors of death. The PET parameters SUVmax
      (p=0.181), SUVmean (p=0.237), MTV (p=0.636), and TLG (p=0.469) did not differ
      significantly between patients with and without EBV infections. CONCLUSIONS: High
      TLG was the only significant predictive factor on relapse free survival. The
      SUVmax and SUVmean measured by F18-FDG PET/CT could be significant prognostic
      factors in patients with extranodal nasal type NK/T cell lymphoma.

PMID- 29056245
TI  - The Cerebellum Is a Common Site of Affection in Leigh Syndrome.

PMID- 29056244
TI  - GRIN2A mutations in epilepsy-aphasia spectrum disorders.
AB  - OBJECTIVE: Epilepsy-aphasia spectrum (EAS) are a group of epilepsy syndromes
      denoting an association between epilepsy, speech disorders and the EEG signature
      of centrotemporal spikes. Mutations in the GRIN2A gene, encoding the NMDA
      glutamate receptor alpha2 subunit were reported in focal epilepsy with speech
      disorder. We aimed to explore the role of GRIN2A mutations in patients with
      centrotemporal spikes related epileptic syndromes in a Chinese cohort. METHODS:
      Patients with Landau-Kleffner syndrome (LKS), epileptic encephalopathy with
      continuous spike-and-wave during sleep (ECSWS), atypical benign partial epilepsy
      (ABPE), and benign epilepsy with centrotemporal spikes (BECTS) were recruited.
      GRIN2A mutation screening was performed using PCR and Sanger sequencing. RESULTS:
      122 patients, including 9 LKS, 26 ECSWS, 42 ABPE and 45 BECTS were enrolled. The
      mean age of seizure or aphasia onset was 5 years, ranging from 10 months to 11
      years. Heterozygous GRIN2A mutations were detected in four patients (G760S,
      D1385Y, C455Y and C231R) GRIN2A mutation was found in 11.1% (1 out of 9 cases) of
      LKS, and in 7.1% (3 out of 42 cases) of ABPE, but in none with ECSWS and BECTS.
      No GRIN2A mutation was found in patients with a family history of febrile
      seizures or epilepsy. CONCLUSION: GRIN2A mutation is a genetic cause in less than
      11% patients with LKS or ABPE. GRIN2A gene is a rare causative gene in Chinese
      patients with EAS, suggesting the possibility of other gene involved in the
      pathogenesis.

PMID- 29056246
TI  - Diagnostic Yield From 339 Epilepsy Patients Screened on a Clinical Gene Panel.
AB  - BACKGROUND: The contribution of genetic factors to epilepsy has long been
      recognized and has been estimated to play a role in 70% to 80% of cases.
      Identification of a pathogenic variant can help families to better cope with the
      disorder, allows for genetic counseling to determine recurrence risk, and in some
      cases, can directly influence treatment options. In this study, we determined the
      diagnostic yield of a clinical gene panel applied to an unselected cohort of
      epilepsy patients. METHODS: Variant reports from 339 clinically referred epilepsy
      patients screened using a 110-gene panel were retrospectively reviewed. Variants
      were classified using the American College of Medical Genetics and Genomics
      guidelines. RESULTS: Pathogenic or likely pathogenic variants were identified in
      62 individuals (18%) and potentially causative variants were identified in an
      additional 21 individuals (6%). Causative and potentially causative variants were
      most frequently identified in SCN1A (n = 15) and KCNQ2 (n = 10). Other genes in
      which disease-causing variants were identified in multiple individuals included
      CDKL5, SCN2A, SCN8A, SCN1B, STXBP1, TPP1, PCDH19, CACNA1A, GABRA1, GRIN2A,
      SLC2A1, and TSC2. Sixteen additional genes had variants identified in single
      individuals. CONCLUSIONS: We identified 87 variants in 30 different genes that
      could explain disease, of which 54% were not previously reported. This study
      confirms the utility of targeted gene panel analysis in epilepsy and highlights
      several factors to improve the yield of diagnostic genetic testing, including the
      critical need for clinical phenotype information and parental samples, microarray
      analysis for whole exon deletions and duplications, and frequent update of panels
      to incorporate new disease genes.

PMID- 29056247
TI  - Haemato-oncology patients' perceptions of health-related quality of life after
      critical illness: A qualitative phenomenological study.
AB  - INTRODUCTION: Haemato-oncology patients often require critical care support due
      to side-effects of treatment. Discharge can mark the start of an uncertain
      journey due to the impact of critical illness on health-related quality of life.
      Qualitatively establishing needs is a priority as current evidence is limited.
      AIMS: To qualitatively explore perceptions of haemato-oncology patients' health
      related quality of life after critical illness and explore how healthcare
      professionals can provide long-term support. METHODS: Nine in-depth interviews
      were conducted three to eighteen months post-discharge from critical care.
      Phenomenology was used to gain deeper understanding of the patients' lived
      experience. SETTING: A 19-bedded Intensive Care Unit in a specialist cancer
      centre. FINDINGS: Five major themes emerged: Intensive care as a means to an end;
      Rollercoaster of illness; Reliance on hospital; Having a realistic/sanguine
      approach; Living in the moment. Haemato-oncology patients who experience critical
      illness may view it as a small part of a larger treatment pathway, thus health
      related quality of life is impacted by this rather than the acute episode.
      CONCLUSIONS: Discharge from the intensive care unit can be seen as a positive end
      point, allowing personal growth in areas such as relationships and living life to
      the full. The contribution of health-care professionals and support of
      significant others is regarded as critical to the recovery experience.

PMID- 29056248
TI  - Concise syntheses and HCV NS5B polymerase inhibition of (2'R)-3 and (2'S)-2'
      ethynyluridine-10 and related nucleosides.
AB  - (2'R)-Ethynyl uridine 3, and its (2'S)-diastereomer 10, are synthesised in a
      divergent fashion from the inexpensive parent nucleoside. Both nucleoside
      analogues are obtained from a total of 5 simple synthetic steps and 3 trivial
      column chromatography purifications. To evaluate their effectiveness against HCV
      NS5B polymerase, the nucleosides were converted to their respective 5'-O
      triphosphates. Subsequently, this lead to the discovery of the 2'-beta-ethynyl 18
      and -propynyl 20 nucleotides having significantly improved potency over
      Sofosbuvir triphosphate 24.

PMID- 29056250
TI  - Fulminant type 1 diabetes mellitus associated with pembrolizumab.

PMID- 29056249
TI  - NEPHRUTIX: A randomized, double-blind, placebo vs Rituximab-controlled trial
      assessing T-cell subset changes in Minimal Change Nephrotic Syndrome.
AB  - Minimal-change nephrotic syndrome (MCNS) is an immune-mediated glomerular
      disease. We have analyzed the modifications on T-cell subsets in twenty-three
      patients who were highly steroid/calcineurin inhibitor and/or mycophenolate
      mofetil-dependent for frequently relapsing nephrotic syndrome (FRNS) and who were
      enrolled in a multicenter, double-blind, randomized, placebo vs Rituximab
      controlled trial. Patients with FRNS entered the trial at remission and were
      randomly assigned to receive either Rituximab or placebo. In both groups, patient
      blood samples were analyzed at inclusion and then monthly until six months post
      perfusion. Disclosure of patient's allocation code occurred in relapse or at the
      end of the trial. All patients under placebo displaying relapse were subsequently
      treated with Rituximab. Despite the significant decrease of immunosuppressive
      drugs, remission was maintained in all patients included in the Rituximab group,
      except one (n = 9/10). On the other hand, relapses occurred within a few weeks
      (means ~ 7.3 weeks) in all patients receiving placebo (n = 13). At inclusion,
      before rituximab therapy, the frequency of different T-cell subsets were highly
      similar in both groups, except for CD8+ and invariant TCRValpha24 T-cell subsets,
      which were significantly increased in patients of the Placebo group ((p = 0,0414
      and p = 0.0428, respectively). Despite the significant decrease of
      immunosuppressive drugs, remission was maintained in all patients included in the
      Rituximab group (n = 10), except one. Relapses were associated with a significant
      decrease in CD4+CD25highFoxP3high Tregulatory cells (p = 0.0005) and IL2
      expression (p = 0.0032), while CMIP abundance was significantly increased (p =
      0.03). Remissions after Rituximab therapy were associated in both groups with
      significant decrease in the frequency of CD4+CD45RO+CXCR5+, invariant natural
      killer T-cells (INKT) and CD4-CD8- (double-negative, DN) T-cells expressing the
      invariant Valpha24 chain (DN-TCR Valpha24) T-cells, suggesting that MCNS involves
      a disorder of innate and adaptive immune response, which can be stabilized by
      Rituximab treatment.

PMID- 29056251
TI  - Metabolic syndrome: first prevalence study in primary care, Honduras.

PMID- 29056252
TI  - Ectopic Cushing's syndrome: Paradoxical effect of somatostatin analogs.

PMID- 29056253
TI  - Potential consequences in children of a testosterone gel used by their fathers.

PMID- 29056254
TI  - Thyroid involvement by Rosai-Dorfman disease.

PMID- 29056255
TI  - Combined sleeve gastrectomy and orthotopic liver transplantation in patient with
      type 2 obesity and advanced liver disease.

PMID- 29056256
TI  - Glibenclamide inhibits NLRP3 inflammasome-mediated IL-1beta secretion in human
      trophoblasts.
AB  - Infection-associated pregnancy complications cause premature delivery. Caspase-1
      is involved in the maturation of interleukin (IL)-1beta, which is activated by
      the NLRP3 inflammasome. To characterize the significance of the NLRP3
      inflammasome pathway in the placenta, the effects of activators and inhibitors on
      NLRP3-related molecules were examined using isolated primary trophoblasts.
      Caspase-1 and IL-1beta mRNA expression was markedly increased in response to
      lipopolysaccharide (LPS), a toll-like receptor (TLR)4 ligand. Treatment with the
      potassium ionophore nigericin significantly increased the level of activated
      caspase-1. Treatment with either LPS or nigericin stimulated IL-1beta secretion,
      whereas pretreatment with the ATP-sensitive K+ channel inhibitor glibenclamide,
      the Rho-associated coiled-coil kinase inhibitor Y-27632, or a caspase-1 inhibitor
      significantly decreased nigericin-induced IL-1beta secretion. In addition,
      dibutyryl-cAMP, which induces trophoblast differentiation, decreased expression
      of NLRP3, caspase-1, and IL-1beta. These findings suggest that trophoblasts can
      secrete IL-1beta through the NLRP3/caspase-1 pathway, which is suppressed by
      glibenclamide, and that the TLR4-mediated NLRP3 inflammasome pathway is more
      likely to be stimulated in undifferentiated than differentiated trophoblasts. Our
      data support the hypothesis that inhibition of the NLRP3 inflammasome can
      suppress placental inflammation-associated disorders.

PMID- 29056258
TI  - Introduction.

PMID- 29056257
TI  - Eating Behaviours and Prevalence of Gastroesophageal Reflux Disease in Japanese
      Adult Patients With Type 2 Diabetes Mellitus: The Dogo Study.
AB  - OBJECTIVES: In the general population, late-night dinner is positively associated
      with gastroesophageal reflux disease (GERD). No evidence exists regarding the
      relationship between eating behaviours and GERD in patients with type 2 diabetes
      mellitus, though the prevalence of GERD in patients with type 2 diabetes is
      higher than in those without diabetes. We conducted this study to investigate the
      association between eating behaviours and GERD in Japanese patients with type 2
      diabetes. METHODS: The study's subjects were 817 Japanese patients with type 2
      diabetes. GERD was defined as being present when a subject had a Quality of Life
      and Utility Evaluation Survey Technology (QUEST) score of 4 or higher. The
      assessment of eating behaviour was performed by self-administered questionnaire.
      Subjects were considered positive for late-night dinner if they answered yes to
      the question "Do you eat dinner within 2 hours before bedtime at least 3 times
      per week? RESULTS: The prevalence values of GERD, skipping breakfast, bedtime
      snacking, late-night dinner and fast eating were 32.0%, 13.7%, 27.1%, 28.8%, and
      44.4%, respectively. Late-night dinner was independently positively associated
      with GERD in patients with type 2 diabetes; the adjusted odds ratio was 1.46 (95%
      CI 1.03 to 2.05). No relationships were found between skipping breakfast, bedtime
      snacking or fast eating and GERD. CONCLUSIONS: Late-night dinner may be
      positively associated with GERD in Japanese patients with type 2 diabetes.

PMID- 29056259
TI  - Relationship Between Left Ventricle Position and Haemodynamic Parameters During
      Cardiopulmonary Resuscitation in a Pig Model.
AB  - BACKGROUND: From the viewpoint of cardiac pump theory, the area of the left
      ventricle (LV) subjected to compression increases as the LV lies closer to the
      sternum, possibly resulting in higher blood flow in patients with LV closer to
      the sternum. However, no study has evaluated LV position during cardiac arrest or
      its relationship with haemodynamic parameters during cardiopulmonary
      resuscitation (CPR). The objectives of this study were to determine whether the
      position of the LV relative to the anterior-posterior axis representing the
      direction of chest compression shifts during cardiac arrest and to examine the
      relationship between LV position and haemodynamic parameters during CPR. METHODS:
      Subcostal view echocardiograms were obtained from 15 pigs with the transducer
      parallel to the long axis of the sternum before inducing ventricular fibrillation
      (VF) and during cardiac arrest. Computed tomography was performed in three pigs
      to objectively observe LV position during cardiac arrest. LV position parameters
      including the shortest distance between the anterior-posterior axis and the mid
      point of the LV chamber (DAP-MidLV), the shortest distance between the anterior
      posterior axis and the LV apex (DAP-Apex), and the area fraction of the LV
      located on the right side of the anterior-posterior axis (LVARight/LVATotal) were
      measured. RESULTS: DAP-MidLV, DAP-Apex, and LVARight/LVATotal decreased
      progressively during untreated VF and basic life support (BLS), and then
      increased during advanced cardiovascular life support (ACLS). A repeated measures
      analysis of variance revealed significant time effects for these parameters.
      During BLS, the end-tidal carbon dioxide and systolic right atrial pressure were
      significantly correlated with the LV position parameters. During ACLS, systolic
      arterial pressure and systolic right atrial pressure were significantly
      correlated with DAP-MidLV and DAP-Apex. CONCLUSIONS: Left ventricular position
      changed significantly during cardiac arrest compared to the pre-arrest baseline.
      LV position during CPR had significant correlations with haemodynamic parameters.

PMID- 29056261
TI  - Discussion.

PMID- 29056260
TI  - Robotic heart surgery: Hype or hope?

PMID- 29056262
TI  - Where there is smoke, is there fire?

PMID- 29056263
TI  - Pattern and predictors of dual antiplatelet use after coronary artery bypass
      graft surgery.
AB  - BACKGROUND: Resumption of dual antiplatelet therapy after coronary artery bypass
      grafting in patients presenting with acute coronary syndrome is recommended, but
      the current practice pattern in the United States remains unknown. We aimed to
      investigate the current pattern of dual antiplatelet therapy use after coronary
      artery bypass grafting at the Yale-New Haven Hospital. METHODS: We conducted a
      single-center retrospective review of patients who presented with acute coronary
      syndrome and underwent coronary artery bypass grafting between 2014 and 2016. The
      primary outcome was hospital discharge with dual antiplatelet therapy. Mixed
      effect multivariate logistic regression was used to evaluate predictors of dual
      antiplatelet therapy use or nonuse, accounting for surgeon-specific preference.
      The discriminatory ability of the model was evaluated with receiver operating
      characteristics analysis. RESULTS: Of 572 patients included, only 29% were
      discharged with dual antiplatelet therapy. In the mixed-effect multivariate model
      isolating surgeon preferences, increase in age (odds ratio, 0.95; 95% confidence
      interval, 0.92-0.98; P < .001) and discharge with anticoagulants (odds ratio,
      0.20; 95% confidence interval, 0.07-0.55; P = .002) were associated with lower
      odds of dual antiplatelet therapy use. Off-pump coronary artery bypass grafting
      compared with on-pump coronary artery bypass grafting was associated with
      increased odds of dual antiplatelet therapy use (odds ratio, 31.5; 95% confidence
      interval, 12.8-77.2; P < .001). C-index of the prediction model was 0.74.
      CONCLUSIONS: The overall rate of dual antiplatelet therapy use in patients with
      acute coronary syndrome who underwent coronary artery bypass grafting was low and
      variable among surgeons. The use or nonuse was guided by previously established
      risk factors of recurrent ischemia and bleeding, along with surgeon preference.

PMID- 29056264
TI  - Performance of the Cox-maze IV procedure is associated with improved long-term
      survival in patients with atrial fibrillation undergoing cardiac surgery.
AB  - OBJECTIVE: Atrial fibrillation (AF) is associated with an increased mortality
      risk. The Cox-maze IV procedure (CM4) performed concomitantly with other cardiac
      procedures has been shown to be effective for restoring sinus rhythm. However,
      few data have been published on the late survival of patients undergoing a
      concomitant CM4. METHODS: Patients undergoing cardiac surgery were
      retrospectively reviewed from 2001 to 2016 (n = 10,859). Patients were stratified
      into 3 groups: patients with a history of AF receiving a concomitant CM4 (CM4; n
      = 438), patients with a history of AF unaddressed during surgery (Untreated AF; n
      = 1510), and patients without AF history (No AF; n = 8911). Propensity score
      matching was conducted between the CM4 and Untreated AF groups, and between the
      CM4 and No AF groups. RESULTS: Thirty-day mortality was similar between the
      matched groups. Kaplan-Meier analysis showed greater survival for CM4 compared to
      Untreated AF (P = .004). Ten-year survival was 62% for CM4 and 42% for Untreated
      AF. Adjusted hazard ratio was 0.47 (95% confidence interval, 0.26-0.86, P =
      .014). No difference in survival was found between CM4 and No AF groups with the
      Kaplan-Meier analysis (P = .847). Ten-year survival was 63% for CM4 and 55% for
      No AF. Adjusted hazard ratio was 1.03 (95% confidence interval, 0.51-2.11, P =
      .929). CONCLUSIONS: For selected patients with a history of AF undergoing cardiac
      surgery, concomitant CM4 did not add significantly to postoperative morbidity or
      mortality and was associated with improved late survival compared with patients
      with untreated AF and a similar survival to patients without a history of AF.

PMID- 29056265
TI  - Robotic mitral repair: Denying the enlightenment.

PMID- 29056266
TI  - The glass is half full.

PMID- 29056267
TI  - Airway ciliary dysfunction: Association with adverse postoperative outcomes in
      nonheterotaxy congenital heart disease patients.
AB  - OBJECTIVE: Heterotaxy (HTX) congenital heart disease (CHD) patients with ciliary
      dysfunction (CD) have been shown to have increased postoperative respiratory
      morbidity. We hypothesized that non-HTX CHD infants with CD also will have
      increased postoperative morbidity, particularly respiratory complications.
      METHODS: Sixty-three infants with non-HTX CHD undergoing cardiac surgery were
      enrolled. Tests commonly used to assess for CD, nasal nitric oxide (nNO)
      measurements and nasal epithelial ciliary motion (CM) assessment, were obtained.
      Baseline characteristics and postoperative outcomes were collected and analyzed.
      RESULTS: Non-HTX CHD infants exhibited a high prevalence of abnormal CM (32%) and
      low nNO (39%). This finding was not correlated with demographics or surgical
      complexity. Infants with abnormal CM had increased odds of requiring noninvasive
      positive pressure ventilation (odds ratio [OR], 6.5; 95% confidence interval
      [CI], 1.5-29.4; P = .016) and respiratory medication use (OR, 4.4; 95% CI, 1.5
      13.3; P = .01). In contrast, infants with low nNO showed evidence of abnormal pre
      and postoperative systolic function (40% vs 4%; P = .004, and 34% vs 13%; P =
      .056, respectively) and had greater odds of acquiring infections (OR, 4.9; 95%
      CI, 1.4-17; P = .014). CONCLUSIONS: Non-HTX CHD infants with abnormal CM showed
      increased postoperative morbidity associated with poor respiratory outcomes. In
      contrast, low nNO correlated with reduced hemodynamic function. These findings
      suggest screening for abnormal CM may allow perioperative interventions to reduce
      pulmonary morbidities. Whether low nNO may prognosticate poor hemodynamic
      function warrants further investigation.

PMID- 29056268
TI  - Successful treatment of a patient with statin-induced myopathy and myotonic
      dystrophy type II with proprotein convertase subtilisin/kexin type 9 inhibitor,
      alirocumab (Praluent).
AB  - Presently there are limited treatment options for hypercholesterolemia in
      patients with statin intolerance and myotonic dystrophy. A 74 year-old male
      presented to endocrine clinic with hypercholesterolemia (serum LDL-C 210 mg/dL),
      hypogonadism, insulin-controlled type 2 diabetes mellitus, and minimally elevated
      serum creatine kinase (CK) levels (184 U/L, ref. range 38-174). Shortly after
      simvastatin treatment, patient developed severe myalgias in the proximal lower
      and upper extremities; and serum CK increased to 317 U/L. Subsequently patient
      was treated with various statins including rosuvastatin with similar outcomes.
      Patient was also treated with bile acid binding resin and ezetimibe without
      improvement. At this time, a diagnosis of myotonic dystrophy type 2 was
      confirmed. Patient was then treated with alirocumab, a PCSK9 inhibitor 75 mg
      subcutaneously every 2 weeks with significant improvement in LDL-C (90 mg/dL) and
      myalgias. In conclusion, PCSK9 inhibitors such as alirocumab may be an excellent
      lipid lowering agent in patients with statin intolerance and myotonic dystrophy.

PMID- 29056269
TI  - Prevalence of low birthweight and macrosomia in a private clinic in North Mexico.

PMID- 29056270
TI  - Primary adrenal insufficiency due to X-linked adrenoleukodystrophy diagnosed in
      adulthood.

PMID- 29056271
TI  - A molybdenum disulfide/reduced graphene oxide fiber coating coupled with gas
      chromatography-mass spectrometry for the saponification-headspace solid-phase
      microextraction of polychlorinated biphenyls in food.
AB  - In this work, the molybdenum disulfide/reduced graphene oxide (MoS2/RGO)
      composite material was synthesized as a fiber coating to extract seven indicator
      polychlorinated biphenyls (PCBs; PCB28, PCB52, PCB101, PCB118, PCB138, PCB153,
      and PCB180) present in food via a saponification-headspace solid-phase
      microextraction assay (saponification-HS-SPME). The MoS2/RGO coating was prepared
      and deposited on a stainless steel wire with the help of a silicone sealant and
      used as an SPME fiber. The alkali solution dissolved the fat and helped in
      releasing the PCBs present in milk to the headspace for extraction under 100
      degrees C. Following desorption in the inlet, the targets were quantified by gas
      chromatography-mass spectrometry. The effects of sorbent dosage, extraction time,
      added salts, and stirring rate on the extraction efficiency were investigated.
      The new coating was able to adsorb a higher amount of analytes, which was about
      1.1-2.9 times in comparison with the commercially available SPME fiber (coated
      with divinylbenzene/carboxen/polydimethylsiloxane). It also showed the highest
      adsorption capability toward PCBs, which was 1.5-2.7 times that of the prepared
      RGO modified fiber. Moreover, MoS2 also showed a strong affinity toward PCBs in a
      manner similar to its affinity for graphene. The developed method is simple and
      environmentally friendly as it does not require any organic solvents.
      Furthermore, it exhibits good sensitivity with detection limits less than 0.1ngmL
      1, linearity (0.25-100ngmL-1), and reproducibility (relative standard deviation
      below 10% for n=3). The novel SPME fibers are inexpensive, reusable, and can be
      easily prepared and manipulated. In addition, the saponification-HS-SPME assay
      was also found to be suitable for screening persistent organic pollutants in
      dairy products.

PMID- 29056272
TI  - Fast determination of alkylphenol ethoxylates in leafy vegetables using a
      modified quick, easy, cheap, effective, rugged, and safe method and ultra-high
      performance supercritical fluid chromatography-tandem mass spectrometry.
AB  - In the present study, a quick and sensitive method was developed for simultaneous
      determination of nonylphenol ethoxylates (NPxEOs) and octylphenol ethoxylates
      (OPxEOs) (x=2-20) in three leafy vegetables, including cabbage, lettuce, and
      spinach using a modified "QuEChERS" method and ultra-high performance
      supercritical fluid chromatography-tandem mass spectrometry (UHPSFC-MS/MS) with
      scheduled multiple reaction monitoring (MRM). Under optimized conditions, the 38
      target analytes were analyzed within a short period of time (5 min). The
      linearities of the matrix-matched standard calibrations were satisfactory with
      coefficients of determination (R2)>0.99 and the limits of detection (LOD) and
      quantification (LOQ) were in between 0.02-0.27 and 0.18-1.75MUgkg-1,
      respectively. The recovery of all target analytes spiked at three (low, medium,
      and high) fortification levels in various leafy vegetables were ranged from 72.8
      122.6% with relative standard deviation (RSD) <=18.3%. The method was
      successfully applied to market samples and the target analytes were found in all
      monitored samples, with total concentrations of 0-8.67MUgkg-1 and 15.75
      95.75MUgkg-1 for OPxEOs and NPxEOs (x=2-20), respectively. In conclusion, the
      newly developed UHPSFC-ESI-MS/MS method is rapid and versatile and could be
      extrapolated for qualitative and quantitative analysis of APxEOs in other leafy
      vegetables.

PMID- 29056273
TI  - Polymer monoliths with silver nanoparticles-cholesterol conjugate as stationary
      phases for capillary liquid chromatography.
AB  - Monoliths in fused-silica capillaries were prepared by an in-situ polymerization
      using glycidyl methacrylate (GMA) as a functional monomer and in the presence of
      different crosslinkers such as ethylene dimethacrylate (EDMA), trimethylolpropane
      trimethacrylate (TRIM), 1,6-hexanediol dimethacrylate (HEDMA), pentaerythritol
      tetraacrylate (PETeA), triethylene glycol dimethacrylate (TriEDMA), while
      azobisisobutyronitrile (AIBN) was an initiator. The monoliths' surfaces were
      modified chemically with cystamine dihydrochloride, followed by immobilization of
      Ag-NPs the surface of which was functionalized with cholesterol cysteamine (Chol
      SH). Such a new material enabled the separation of proteins in a reversed phase
      mode. The influence of the kind of a cross-linker and composition of the
      porogenic solutions on the porosity and separation properties of the obtained
      polymers was investigated and discussed. It was found that the amount of Ag-NPs
      embedded on the monoliths' surfaces depended on the porous properties of the
      monoliths, which was directly connected with the kind of the cross-linkers used.
      For the determination of the amount of the attached Ag-NPs the thermogravimetric
      analysis was used and additionally the ISEC method as a comparative method was
      also proposed. It was found that the maximum amount (about 20% by weight) of the
      10nm Ag-NPs was attached to the poly(GMA-EDMA) and poly(GMA-TRIM) monoliths.

PMID- 29056274
TI  - Development and validation of a method for the determination of regulated
      fragrance allergens by High-Performance Liquid Chromatography and Parallel Factor
      Analysis 2.
AB  - This work presents the development and validation of a multivariate method for
      quantitation of 6 potentially allergenic substances (PAS) related to fragrances
      by ultrasound-assisted emulsification microextraction coupled with HPLC-DAD and
      PARAFAC2 in the presence of other 18 PAS. The objective is the extension of a
      previously proposed univariate method to be able to determine the 24 PAS
      currently considered as allergens. The suitability of the multivariate approach
      for the qualitative and quantitative analysis of the analytes is discussed
      through datasets of increasing complexity, comprising the assessment and
      validation of the method performance. PARAFAC2 showed to adequately model the
      data facing up different instrumental and chemical issues, such as co-elution
      profiles, overlapping spectra, unknown interfering compounds, retention time
      shifts and baseline drifts. Satisfactory quality parameters of the model
      performance were obtained (R2>=0.94), as well as meaningful chromatographic and
      spectral profiles (r>=0.97). Moreover, low errors of prediction in external
      validation standards (below 15% in most cases) as well as acceptable
      quantification errors in real spiked samples (recoveries from 82 to 119%)
      confirmed the suitability of PARAFAC2 for resolution and quantification of the
      PAS. The combination of the previously proposed univariate approach, for the well
      resolved peaks, with the developed multivariate method allows the determination
      of the 24 regulated PAS.

PMID- 29056275
TI  - Current and Future Applications of Novel Immunotherapies in Urological Oncology:
      A Critical Review of the Literature.
AB  - CONTEXT: Immunotherapies promote anticancer responses with varying levels of
      success based on the tumor type. OBJECTIVE: In this narrative review article, we
      searched the literature regarding immunotherapies in genitourinary malignancies
      to define the state of the field, explore future applications of immune
      checkpoint inhibitors, cytokines, vaccines, and cellular therapies in urological
      oncology and evaluate possible strategies to improve the selection of patients
      who might benefit from such approaches. EVIDENCE ACQUISITION: We reviewed related
      literature, with a focus on recent studies about immunotherapies, predictors of
      response, and ongoing clinical trials. EVIDENCE SYNTHESIS: Immunotherapies based
      on immune checkpoint blockade are approved as first- and second-line therapies
      for urothelial carcinoma (UC) and second-line therapies for renal cell carcinoma
      with limited success in prostate cancer. Programmed death-ligand 1 is the most
      commonly used predictive biomarker outside of UC; however, a substantial
      proportion of patients with tumors negative for programmed death-ligand 1
      expression benefit from checkpoint inhibition, limiting its sensitivity. A high
      mutational load and molecular subtypes of UC are emerging as additional potential
      predictors. Genomic sequencing and gene expression analysis associate alterations
      of genes implicated in DNA repair pathways, such as BRCA1 and BRCA2, with immune
      checkpoint therapies. In prostate cancer, the vaccine, sipuleucel-T, is the only
      Food and Drug Administration-approved immunotherapy. CONCLUSIONS: Immunotherapies
      are emerging as exciting new treatment options with a tolerable toxicity profile
      in urological cancers. Checkpoint inhibitors are effective only in a subset of
      patients, demanding personalized approaches that consider various clinical and
      molecular parameters to predict patient response. Clinical trials investigating
      the optimal timing, sequence, and combination of immunotherapies with standard of
      care and novel agents will guide therapy choices and improve patient outcome.
      PATIENT SUMMARY: Clinical data supports the safety and efficacy of immune
      checkpoint inhibitors alone or in combination with other therapies in urological
      cancers.

PMID- 29056276
TI  - Phone coaching, glycemic control and diabetes unit visits in patients treated
      with insulin.

PMID- 29056277
TI  - Endocrinology and nutrition: Evolution of the choice of specialty in the last
      years.

PMID- 29056278
TI  - Influence of iodine status on maternal thyroid function during pregnancy.

PMID- 29056279
TI  - Autonomic enteropathy: A frequently ignored diabetic complication.

PMID- 29056280
TI  - Intratumoral activating GNAS (R201C) mutation in two unrelated patients with
      virilizing ovarian Leydig cell tumors.

PMID- 29056281
TI  - Adrenal insufficiency and exogenous Cushing's syndrome in a patient receiving
      inhaled fluticasone and ritonavir.

PMID- 29056282
TI  - Editorial Comment.

PMID- 29056283
TI  - Fat mass to fat-free mass ratio reference values from NHANES III using
      bioelectrical impedance analysis.
AB  - BACKGROUND & AIM: Low fat-free mass (FFM) or high fat mass (FM) are abnormal body
      composition phenotypes associated with morbidity. These conditions in combination
      lead to worse health outcomes, and can be identified by a high FM/FFM ratio.
      Here, we developed sex, age, and body mass index (BMI) stratified, population
      based FM/FFM reference values using bioelectrical impedance analysis (BIA)
      measurements. METHODS: White, non-Hispanic individuals aged 18-90 years old with
      data for weight, stature and BIA resistance measures from the third National
      Health and Nutrition Examination Survey (NHANES) III were included. Previously
      validated and sex-specific BIA prediction equations were used to calculate FM and
      FFM. FM/FFM values were generated at 5th, 50th and 95th percentiles for each sex,
      age (18-39.9, 40-59.9, 60-69.9 and 70-90 years), and BMI category (underweight,
      normal weight, overweight, class I/II and class III obesity). RESULTS: A total of
      6372 individuals who had estimated FM and FFM values were identified (3366
      females, 3006 males). Median values of FM/FFM were 0.24 and 0.40 for young
      (<=39.9 years) males and females with normal BMI, and 0.34 for males and 0.59 for
      females who were overweight. For elderly individuals aged >70 years, median
      FM/FFM for males and females were respectively 0.28 and 0.45 for those with
      normal BMI, and 0.37 and 0.61 for those in the overweight category. CONCLUSIONS:
      These FM/FFM reference values provide information on body composition
      characteristics that account for age, sex and BMI, which can be useful to
      identify individuals at risk for body composition abnormalities.

PMID- 29056284
TI  - A systematic review of the epidemiology, pathophysiology and current management
      of hyperlipidaemic pancreatitis.
AB  - BACKGROUND & AIMS: The aims of this systematic review were to define the
      epidemiology and pathophysiology of hyperlipidaemic pancreatitis, establish its
      association with clinical outcome and define management strategies. METHODS: The
      Cochrane, Embase and Medline databases were searched, limited to the last decade,
      for articles on hyperlipidaemic pancreatitis. All randomised controlled trials,
      observational studies and case series (with a minimum of 10 patients) on
      hyperlipidaemic pancreatitis were included. RESULTS: Thirty-eight studies with
      1979 patients were included. The median admission triglyceride concentration was
      42.8 mmol/L (range 13.6-108.6 mmol/L) [3785 mg/dL (range 1205-9612 mg/dL)].
      Severe hypertriglyceridaemia (>1000 mg/dL, 11.0 mmol/L) was present in 1.7% of
      the adult population, and about 15-20% of these developed hyperlipidaemic acute
      pancreatitis. Medical management of severe hyperlipidaemia at onset of acute
      pancreatitis has not been investigated fully. However, tight regulation of
      triglyceride concentration after presentation with acute pancreatitis was found
      to reduce the risk of recurrence. Plasmapheresis reduced concentrations of
      triglycerides by up to 85%, but this did not impact morbidity or mortality. All
      studies included defined hyperlipidaemia as a more severe form of pancreatitis.
      CONCLUSION: The available evidence suggests an increasing risk of acute
      pancreatitis in patients with hyperlipidaemia and a more severe form of
      pancreatitis. There is some evidence to suggest biochemical benefit of using
      novel techniques like plasmapheresis without the desired physiological benefit.
      However, there is a need for an international consensus on the management of
      hyperlipidaemic pancreatitis. More rigorous and methodologically robust studies
      are required to inform such consensus guidelines.

PMID- 29056285
TI  - The role of multimodal imaging in stroke code patients.
AB  - In stroke code patients, multimodal imaging workup encompasses various imaging
      techniques, including baseline computed tomography (CT), magnetic resonance (MR)
      imaging, diffusion MR imaging, CT or MR perfusion studies, and CT or MR
      angiography, that are used to rule out bleeding, confirm arterial occlusion,
      establish tissue viability, and help select candidates for endovascular treatment
      as early as possible. Five recently published relevant clinical trials have
      demonstrated the efficacy of mechanical thrombectomy in proximal arterial
      occlusions; all these trials used different imaging techniques to select
      patients. Analyzing these trials and the scientific literature, we conclude that
      conventional CT interpreted with the Alberta Stroke Programme Computed Tomography
      Score (ASPECTS) and CT or MR angiography should always be used (level of evidence
      I, grade of recommendation A) and that CT and MR perfusion studies are useful in
      specific circumstances.

PMID- 29056286
TI  - Methotrexate-associated osteonecrosis of the jaw: A report of two cases.
AB  - There has been a rise in medication-related osteonecrosis of the jaw (MRONJ)
      predominantly related to antiresorptive and antiangiogenic medications. More
      evidence is revealing that MRONJ is not limited to these drug groups. With the
      introduction of newer and varied medications used in the treatment of cancer and
      autoimmune diseases, reports of possible related osteonecrosis of the jaw (ONJ)
      are also on the rise. We present 2 cases of ONJ in patients with long-standing
      arthritis treated with methotrexate in the absence of a lymphoproliferative
      disorder and antiresorptive or antiangiogenic medications.

PMID- 29056287
TI  - Evaluation of KGF, EGF, VEGF, bcl-2, IL-6 and ki67 expression in oral epithelium
      adjacent to bisphosphonate-related osteonecrosis and florid osseous dysplasia: a
      comparative immunohistochemical study.
AB  - OBJECTIVE: The aim of this study was to compare the expression of proliferative
      markers and apoptosis-associated proteins in the oral mucosa adjacent to bone
      sequestrum associated with osteonecrosis (ON) of the jaws and florid osseous
      dysplasia (OD). STUDY DESIGN: Oral mucosal samples derived from surgical
      procedures performed for treatment of ON and OD (10 cases each) were retrieved.
      Histologic analysis was done on hematoxylin and eosin-stained slides;
      immunohistochemical reactions against epidermal growth factor (EGF), keratinocyte
      growth factor (KGF), vascular endothelial growth factor (VEGF), Bcl-2 protein,
      interleukin-6 (IL-6), and Ki-67 antigen were performed with the immunoperoxidase
      technique. RESULTS: The epithelium was hyperplastic in 60% and 22% of ON and OD
      samples, respectively. Cytoplasmic EGF and KGF expression; Bcl-2, VEGF, and IL-6
      expressions; and the mean epithelial proliferative index were not statistically
      different between the 2 groups. Membranous EGF expression was more evident in
      samples showing hyperplastic epithelium. CONCLUSIONS: Exposure to bisphosphonates
      did not alter the expression of KGF, EGF, VEGF, Bcl-2, IL-6, and the epithelial
      proliferating index in comparison with inflamed oral mucosa not exposed to
      bisphosphonates.

PMID- 29056288
TI  - Evaluation of an experimental oblique plate for osteosynthesis of mandibular
      condyle fractures.
AB  - OBJECTIVE: The aim of this study was to test the bone thickness and potential
      screw length for osteosynthesis of condylar base fractures (according to the
      Loukota classification) with an experimental titanium plate, placed in an ideal
      position against 2 types of conventional plates. STUDY DESIGN: After exclusion of
      completely edentulous mandibles, 28 dentate macerated mandibles available at the
      time of the study were included. Linear regression models 1 and 2 compared the
      sums of the 2 cranial bone thicknesses and the 3 caudal thicknesses among the 3
      different plate designs, and linear models 3 and 4 tested the bone thickness in
      the 2 most cranial screw axes. RESULTS: Linear models 1 and 2 revealed
      significantly higher potential screw lengths for the experimental oblique plate.
      Equally, linear models 3 and 4 indicated significantly higher bone thickness for
      the novel oblique plate. CONCLUSION: The novel proposed oblique plate allows for
      favorable plate positioning in a biomechanically ideal location with sufficient
      amounts of local bone for stable plate fixation. When plates with 15-degree
      angulated screw holes are used, stable bicortical plate fixation can be achieved.

PMID- 29056289
TI  - Genomic and epigenetic characterization for the comparison of synchronous
      bilateral tongue squamous cell carcinomas-A case report.
AB  - : The tongue is the most common and aggressive site for tumors in the oral
      cavity. These tumors are usually located in the lateral border of the tongue and
      are often related to the use of tobacco and alcohol. Clinical management of these
      tumors is predominantly based on anatomic location and TNM classification. The
      identification of molecular signatures with ability to explain the different
      outcomes observed in these patients is of paramount importance to guide and help
      their management. CASE PRESENTATION: we herein describe an 88-year-old woman
      diagnosed with synchronous bilateral tongue carcinoma. This woman did not present
      the traditional risk factors related to oral cancer-alcohol, tobacco, or presence
      of human papiloma virus (HPV). Both tumors were classified by a pathologist as
      pT2. This patient was submitted to surgery, 6 months later was diagnosed with
      cervical metastasis and in the following 2 months died. Copy number alterations
      and methylation status of these 2 simultaneous tumors were analyzed using array
      comparative genomic hybridization, multiplex ligation-dependent probe
      amplification, and methylation specific multiplex ligation-dependent probe
      amplification. In conclusion, in both tumors we identified several molecular
      traits usually found among oral cavity tumors and some of those have been
      associated with clinical outcome, reinforcing their importance to accurately
      establish biomarkers with clinical applicability. Specific genomic and epigenetic
      signatures for each of these 2 tumors were also observed allowing their molecular
      discrimination. The tumor of the right side of the tongue exhibited more copy
      number gains than the tumor of the left side. In the left side tumor less and
      smaller copy number alterations and more methylated genes were observed, which
      could be indicative of an early phase of tumor development. This case shows the
      molecular heterogeneity of oral cavity tumors even in the same patient and
      anatomic site, which could be the key to explain the different outcomes of oral
      tumor patients.

PMID- 29056290
TI  - The extent of edema and tumor synchronous invasion into the subventricular zone
      and corpus callosum classify outcomes and radiotherapy strategies of
      glioblastomas.
AB  - BACKGROUND AND PURPOSE: Irradiating glioblastoma preoperative edema (PE) remains
      controversial. We investigated the associations between tumors' PE extent with
      invasion into synchronous subventricular zone and corpus callosum (sSVZCC) and
      treatment outcomes to provide the clinical evidence for radiotherapy decision
      making. MATERIAL AND METHODS: Extensive PE (EPE) was defined as PE extending >=2
      cm from the tumor edge and extensive progressive disease (EPD) as tumors
      spreading >=2 cm from the preoperative tumor edge along PE. The survival and
      progression patterns were analyzed according to EPE and sSVZCC invasion. RESULTS:
      In total, 136 patients were followed for a median of 74.9 (range, 47.6-102.1)
      months. The median overall survival and progression-free survival were 19.7
      versus 28.6 months (p = 0.005) and 11.0 versus 17.4 months (p = 0.011) in
      patients with EPE+ versus EPE-, and were 18.7 versus 25.4 months (p = 0.021) and
      10.7 versus 14.6 months (p = 0.020) in those with sSVZCC+ versus sSVZCC-. The EPD
      rates for tumors with EPE-/sSVZCC-, EPE-/sSVZCC+, EPE+/sSVZCC-, and EPE+/sSVZCC+
      were 2.8%, 7.1%, 37.0%, and 71.9%, respectively. In EPE+/sSVZCC+, tumor migration
      was associated with the PE extending along the corpus callosum (77.8%) and
      subventricular zone (50.0%). CONCLUSIONS: Our results support the need for
      developing individualized irradiation strategies for glioblastomas according to
      EPE and sSVZCC.

PMID- 29056291
TI  - An in vivo model of a mechanically-induced bone marrow lesion.
AB  - Bone marrow lesions (BMLs) are radiologic abnormalities in magnetic resonance
      images of subchondral bone that are correlated with osteoarthritis. Little is
      known about the physiologic processes within a BML, although BMLs are associated
      with mechanical stress, bone tissue microdamage and increased bone remodeling.
      Here we establish a rabbit model to study the pathophysiology of BMLs. We
      hypothesized that in vivo loads that generate microdamage in cancellous bone
      would also create BMLs and increase bone remodeling. In vivo cyclic loading (0.2
      2.0 MPa in compression for 10,000 cycles at 2 Hz) was applied to epiphyseal
      cancellous bone in the distal femurs of New Zealand white rabbits (n=3, right
      limb loaded, left limb controls experienced surgery but no loading). Magnetic
      resonance images were collected using short tau inversion recovery (STIR) and T1
      weighted sequences at 1 and 2 weeks after surgery/loading and histological
      analysis of the BML was performed after euthanasia to examine tissue microdamage
      and remodeling. Loaded limbs displayed BMLs while control limbs showed only a
      small BML-like signal caused by surgery. Histological analysis of the BML at 2
      weeks after loading showed increased tissue microdamage (p=0.03) and bone
      resorption (p=0.01) as compared to controls. The model described here displays
      the hallmarks of load-induced BMLs, supporting the use of the model to examine
      changes in bone during the development, progression and treatment of BMLs.

PMID- 29056292
TI  - Epigenetics and gene expression profile in first-episode psychosis: The role of
      childhood trauma.
AB  - Childhood Trauma (CT) mediation of the epigenome and its impact on gene
      expression profile could provide a mechanism for the gene-environment interaction
      underling psychosis. We reviewed the evidence concerning epigenetic and gene
      expression modifications associated with CT in both First-Episode Psychosis (FEP)
      and healthy subjects. In order to explore the relative role of psychosis itself
      in determining these modifications, evidence about FEP and epigenetics/gene
      expression was also summarized. We performed a systematic search on PubMed, last
      updated in December 2016. Out of 2966 potentially relevant records, only 41
      studies were included. CT resulted associated: in FEP subjects, with global DNA
      hypo-methylation and reduced BDNF gene-expression; in healthy subjects, with
      hyper-methylation of SLC6A4, NR3C1, KITLG, and OXTR; hypo-methylation of FKBP5,
      IL-6, and BDNF; increased IL1B, IL8, and PTGS gene expression; and decreased
      SLC6A4 gene expression. FEP showed global DNA hypo-methylation; increased
      methylation and reduced gene expression of GCH1; hyper-expression of MPB, NDEL1,
      AKT1, and DICER1; and hypo-expression of DROSHA, COMT, and DISC1 in comparison
      with healthy controls.

PMID- 29056295
TI  - Neuroplastin and Basigin Are Essential Auxiliary Subunits of Plasma Membrane Ca2+
      ATPases and Key Regulators of Ca2+ Clearance.
AB  - Plasma membrane Ca2+-ATPases (PMCAs), a family of P-type ATPases, extrude Ca2+
      ions from the cytosol to the extracellular space and are considered to be key
      regulators of Ca2+ signaling. Here we show by functional proteomics that native
      PMCAs are heteromeric complexes that are assembled from two pore-forming PMCA1-4
      subunits and two of the single-span membrane proteins, either neuroplastin or
      basigin. Contribution of the two Ig domain-containing proteins varies among
      different types of cells and along postnatal development. Complex formation of
      neuroplastin or basigin with PMCAs1-4 occurs in the endoplasmic reticulum and is
      obligatory for stability of the PMCA proteins and for delivery of PMCA complexes
      to the surface membrane. Knockout and (over)-expression of both neuroplastin and
      basigin profoundly affect the time course of PMCA-mediated Ca2+ transport, as
      well as submembraneous Ca2+ concentrations under steady-state conditions.
      Together, these results establish neuroplastin and basigin as obligatory
      auxiliary subunits of native PMCAs and key regulators of intracellular Ca2+
      concentration.

PMID- 29056293
TI  - The Molecular Basis of Noncanonical Bacterial Morphology.
AB  - Bacteria come in a wide variety of shapes and sizes. The true picture of
      bacterial morphological diversity is likely skewed due to an experimental focus
      on pathogens and industrially relevant organisms. Indeed, most of the work
      elucidating the genes and molecular processes involved in maintaining bacterial
      morphology has been limited to rod- or coccal-shaped model systems. The
      mechanisms of shape evolution, the molecular processes underlying diverse shapes
      and growth modes, and how individual cells can dynamically modulate their shape
      are just beginning to be revealed. Here we discuss recent work aimed at advancing
      our knowledge of shape diversity and uncovering the molecular basis for shape
      generation in noncanonical and morphologically complex bacteria.

PMID- 29056294
TI  - Enhanced AMPA Receptor Trafficking Mediates the Anorexigenic Effect of Endogenous
      Glucagon-like Peptide-1 in the Paraventricular Hypothalamus.
AB  - Glucagon-like Peptide 1 (GLP-1)-expressing neurons in the hindbrain send robust
      projections to the paraventricular nucleus of the hypothalamus (PVN), which is
      involved in the regulation of food intake. Here, we describe that stimulation of
      GLP-1 afferent fibers within the PVN is sufficient to suppress food intake
      independent of glutamate release. We also show that GLP-1 receptor (GLP-1R)
      activation augments excitatory synaptic strength in PVN corticotropin-releasing
      hormone (CRH) neurons, with GLP-1R activation promoting a protein kinase A (PKA)
      dependent signaling cascade leading to phosphorylation of serine S845 on GluA1
      AMPA receptors and their trafficking to the plasma membrane. Finally, we show
      that postnatal depletion of GLP-1R in the PVN increases food intake and causes
      obesity. This study provides a comprehensive multi-level (circuit, synaptic, and
      molecular) explanation of how food intake behavior and body weight are regulated
      by endogenous central GLP-1. VIDEO ABSTRACT.

PMID- 29056296
TI  - Task Demands Predict a Dynamic Switch in the Content of Awake Hippocampal Replay.
AB  - Reactivation of hippocampal place cell sequences during behavioral immobility and
      rest has been linked with both memory consolidation and navigational planning.
      Yet it remains to be investigated whether these functions are temporally
      segregated, occurring during different behavioral states. During a self-paced
      spatial task, awake hippocampal replay occurring either immediately before
      movement toward a reward location or just after arrival at a reward location
      preferentially involved cells consistent with the current trajectory. In
      contrast, during periods of extended immobility, no such biases were evident.
      Notably, the occurrence of task-focused reactivations predicted the accuracy of
      subsequent spatial decisions. Additionally, during immobility, but not periods
      preceding or succeeding movement, grid cells in deep layers of the entorhinal
      cortex replayed coherently with the hippocampus. Thus, hippocampal reactivations
      dynamically and abruptly switch between operational modes in response to task
      demands, plausibly moving from a state favoring navigational planning to one
      geared toward memory consolidation.

PMID- 29056297
TI  - Virus-Mediated Genome Editing via Homology-Directed Repair in Mitotic and
      Postmitotic Cells in Mammalian Brain.
AB  - Precise genome editing via homology-directed repair (HDR) in targeted cells,
      particularly in vivo, provides an invaluable tool for biomedical research.
      However, HDR has been considered to be largely restricted to dividing cells,
      making it challenging to apply the technique in postmitotic neurons. Here we show
      that precise genome editing via HDR is possible in mature postmitotic neurons as
      well as mitotic cells in mice brain by combining CRISPR-Cas9-mediated DNA
      cleavage and the efficient delivery of donor template with adeno-associated virus
      (AAV). Using this strategy, we achieved efficient tagging of endogenous proteins
      in primary and organotypic cultures in vitro and developing, adult, aged, and
      pathological brains in vivo. Thus, AAV- and CRISPR-Cas9-mediated HDR will be
      broadly useful for precise genome editing in basic and translational
      neuroscience.

PMID- 29056298
TI  - Age-Dependent Dopaminergic Neurodegeneration and Impairment of the Autophagy
      Lysosomal Pathway in LRRK-Deficient Mice.
AB  - LRRK2 mutations are the most common genetic cause of Parkinson's disease, but
      LRRK2's normal physiological role in the brain is unclear. Here, we show that
      inactivation of LRRK2 and its functional homolog LRRK1 results in earlier
      mortality and age-dependent, selective neurodegeneration. Loss of dopaminergic
      (DA) neurons in the substantia nigra pars compacta (SNpc) and of noradrenergic
      neurons in the locus coeruleus is accompanied with increases in apoptosis,
      whereas the cerebral cortex and cerebellum are unaffected. Furthermore, selective
      age-dependent neurodegeneration is only present in LRRK-/-, not LRRK1-/- or LRRK2
      /- brains, and it is accompanied by increases in alpha-synuclein and impairment
      of the autophagy-lysosomal pathway. Quantitative electron microscopy (EM)
      analysis revealed age-dependent increases of autophagic vacuoles in the SNpc of
      LRRK-/- mice before the onset of DA neuron loss. These findings revealed an
      essential role of LRRK in the survival of DA neurons and in the regulation of the
      autophagy-lysosomal pathway in the aging brain.

PMID- 29056299
TI  - Development and Refinement of Functional Properties of Adult-Born Neurons.
AB  - New neurons appear only in a few regions of the adult mammalian brain and become
      integrated into existing circuits. Little is known about the functional
      development of individual neurons in vivo. We examined the functional life
      history of adult-born granule cells (abGCs) in the olfactory bulb using
      multiphoton imaging in awake and anesthetized mice. We found that abGCs can
      become responsive to odorants soon after they arrive in the olfactory bulb.
      Tracking identified abGCs over weeks revealed that the robust and broadly tuned
      responses of most newly arrived abGCs gradually become more selective over a
      period of ~3 weeks, but a small fraction achieves broader tuning with maturation.
      Enriching the olfactory environment of mice prolonged the period over which abGCs
      were strongly and broadly responsive to odorants. Our data offer direct support
      for rapid integration of adult-born neurons into existing circuits, followed by
      experience-dependent refinement of their functional connectivity.

PMID- 29056300
TI  - Screening Children at Risk for Retinoblastoma: Consensus Report from the American
      Association of Ophthalmic Oncologists and Pathologists.
AB  - PURPOSE: To provide a set of surveillance guidelines for children at risk for
      development of retinoblastoma. DESIGN: Consensus panel. PARTICIPANTS: Expert
      panel of ophthalmic oncologists, pathologists, and geneticists. METHODS: A group
      of members of the American Association of Ophthalmic Oncologists and Pathologists
      (AAOOP) with support of the American Association for Pediatric Ophthalmology and
      Strabismus and the American Academy of Pediatrics (AAP) was convened. The panel
      included representative ophthalmic oncologists, pathologists, and geneticists
      from retinoblastoma referral centers located in various geographic regions who
      met and discussed screening approaches for retinoblastoma. A patient "at risk"
      was defined as a person with a family history of retinoblastoma in a parent,
      sibling, or first- or second-degree relative. MAIN OUTCOME MEASURES: Screening
      recommendations for children at risk for retinoblastoma. RESULTS: Consensus
      statement from the panel: (1) Dedicated ophthalmic screening is recommended for
      all children at risk for retinoblastoma above the population risk. (2) Frequency
      of examinations is adjusted on the basis of expected risk for RB1 mutation. (3)
      Genetic counseling and testing clarify the risk for retinoblastoma in children
      with a family history of the disease. (4) Examination schedules are stratified on
      the basis of high-, intermediate-, and low-risk children. (5) Children at high
      risk for retinoblastoma require more frequent screening, which may preferentially
      be examinations under anesthesia. CONCLUSIONS: Risk stratification including
      genetic testing and counseling serves as the basis for screening of children at
      elevated risk for development of retinoblastoma.

PMID- 29056301
TI  - Comparison of visual outcomes, alignment accuracy, and surgical time between 2
      methods of corneal marking for toric intraocular lens implantation.
AB  - PURPOSE: To compare the efficacy of a computer-assisted marker system for toric
      intraocular lenses (IOLs) (Callisto Eye System) with manual marking techniques.
      SETTING: University Eye Hospital Munich, Ludwig-Maximilians-University, Munich,
      Germany. DESIGN: Prospective case series. METHODS: This study included patients
      having cataract surgery with implantation of a toric IOL (Torbi 709 M). They were
      randomly assigned to 1 of 2 groups based on the marking system used, manual or
      digital. Patients were included if they had age-related cataract and a regular
      corneal astigmatism of 1.25 diopters (D) or higher. Visual and refractive
      outcomes as well as rotational stability were evaluated. Vector analysis was
      performed to evaluate total astigmatic changes. RESULTS: The study comprised 57
      eyes of 29 patients; there were 28 eyes in the manual group and 29 eyes in the
      digital group. The mean toric IOL misalignment was significantly lower in the
      digital group than in the manual group (2.0 degrees +/- 1.86 [SD] versus 3.4 +/-
      2.37 degrees; P = .026). The mean deviation from the target induced astigmatism
      was significantly lower in the digital group (0.10 +/- 0.08 D versus 0.22 +/-
      0.14 D; P = .008). During surgery, the mean toric IOL alignment time was
      significantly shorter in the digital group (37.2 +/- 11.9 seconds versus 59.4 +/-
      15.3 seconds; P = .003). The mean overall time required to perform the surgery
      was significantly shorter in the digital group (727.2 +/- 198.4 seconds versus
      1110.0 +/- 382.2 seconds; P < .001). CONCLUSIONS: A digital tracking approach for
      toric IOL alignment was efficient and safe to improve refractive outcomes.
      Furthermore, image-guided surgery helped streamline the workflow in refractive
      cataract surgery.

PMID- 29056302
TI  - Single-pass four-throw pupilloplasty: Postoperative mydriasis and fundus
      visibility in pseudophakic eyes.
AB  - PURPOSE: To analyze the pharmacological mydriasis and the consequent fundus
      visibility after single-pass 4-throw pupilloplasty in pseudophakic eyes. SETTING:
      Dr. Agarwal's Eye Hospital, Chennai, India. DESIGN: Comparative case series.
      METHODS: Patients with bilateral pseudophakia with single-pass 4-throw
      pupilloplasty in 1 eye (study) and no single-pass 4-throw in the fellow eye
      (control) were included. The pupil measurements were analyzed before and after
      the instillation of mydriatics (tropicamide 0.8%-phenylephrine 5.0% and atropine
      1.0%). The dimensions at the baseline and 40, 90, and 120 minutes after
      instillation were quantified by anterior-segment optical coherence tomography
      (Visante), a corneal topographer (Orbscan 11z), and an autorefractometer (HRK
      7000). The serial photograph (DC3 digital camera) and the fundus imaging
      (TRC.50DX) were recorded. Changes in pupil size, area, and fundus visibility (50
      degrees); the difference in mydriasis between the drugs; and a comparison of
      mydriasis with the fellow eyes were recorded. RESULTS: The study comprised 22
      patients (22 study eyes and 22 control eyes). There was a significant increase in
      pupil size and area over time (P < .0001). The occurrence of mydriasis was higher
      in the vertical axis (mean 4.5 mm +/- 1.3 [SD]) than in the horizontal axis (mean
      4.0 +/- 1.3 mm) with a significant difference (P = .021). There was a
      statistically significant difference in pupil dilation between the study eyes and
      the control eyes (P = .002). The fundus imaging showed good illumination in 13
      eyes (59%) and defective illumination in 9 eyes (41%) for retinal visibility.
      CONCLUSION: Although pharmacological pupil mydriasis was not equivalent to normal
      eyes, significant mydriasis occurred and aided in fundus visualization after
      single-pass 4-throw pupilloplasty.

PMID- 29056303
TI  - Visual and refractive associations with falls after first-eye cataract surgery.
AB  - PURPOSE: To clarify the effect of first-eye cataract surgery on the incidence of
      falls and identify components of visual function associated with fall risk.
      SETTING: Eight public hospital eye clinics in Sydney, Melbourne, and Perth,
      Australia. DESIGN: Prospective cohort study. METHODS: The study recruited
      patients who had bilateral cataract, were aged 65 years or older, and were on
      public hospital cataract surgery waiting lists. Comprehensive assessments of
      vision, physical function, and exercise activity were performed before and after
      first-eye cataract surgery. Falls were reported prospectively for up to 2 years
      and associations with falls were assessed using generalized linear mixed models.
      RESULTS: Of the 329 patients recruited, 196 (66.6%) completed first-eye surgery
      within the study period. First-eye cataract surgery reduced incident falls by 33%
      (adjusted incidence rate ratio 0.67; 95% confidence interval [CI], 0.49-0.92; P =
      .01). Poorer dominant-eye visual acuity was associated with falls during the
      study timeline (incidence rate ratio, 2.20; 95% CI, 1.02-4.74; P = .04). Patients
      with larger than a spherical equivalent of +/-0.75 diopter change in the
      spectacle lens (operated eye) had a 2-fold greater incidence of falls in the
      period after first-eye cataract surgery than those with less or no change in lens
      power (incidence rate ratio, 2.17; 95% CI, 1.23-3.85; P = .008). CONCLUSIONS:
      First-eye cataract surgery significantly reduced incident falls. Major changes in
      the dioptric power of spectacle correction of the operated eye after surgery
      increased the fall risk. Cautious postoperative refractive management is
      important to maximize the benefit of cataract surgery as a fall-prevention
      measure.

PMID- 29056304
TI  - Cost-utility analyses of cataract surgery in vision-threatening diabetic
      retinopathy.

PMID- 29056305
TI  - Exotoxins and endotoxins: Inducers of inflammatory cytokines.
AB  - Endotoxins and exotoxins are among the most potent bacterial inducers of
      cytokines. During infectious processes, the production of inflammatory cytokines
      including tumor necrosis factor (TNF), interleukin-1beta (IL-1beta), gamma
      interferon (IFNgamma) and chemokines orchestrates the anti-infectious innate
      immune response. However, an overzealous production, leading up to a cytokine
      storm, can be deleterious and contributes to mortality consecutive to sepsis or
      toxic shock syndrome. Endotoxins of Gram-negative bacteria (lipopolysaccharide,
      LPS) are particularly inflammatory because they generate auto-amplificatory loops
      after activation of monocytes/macrophages. LPS and numerous pore-forming
      exotoxins also activate the inflammasome, the molecular platform that allows the
      release of mature IL-1beta and IL-18. Among exotoxins, some behave as
      superantigens, and as such activate the release of cytokines by T-lymphocytes. In
      most cases, pre-exposure to exotoxins enhances the cytokine production induced by
      LPS and its lethality, whereas pre-exposure to endotoxin usually results in
      tolerance. In this review we recall the various steps, which, from the very early
      discovery of pyrogenicity induced by bacterial products, ended to the discovery
      of the endogenous pyrogen. Furthermore, we compare the specific characteristics
      of endotoxins and exotoxins in their capacity to induce inflammatory cytokines.

PMID- 29056306
TI  - Imaging in focus: Imaging the dynamics of endocytosis.
AB  - Endocytosis, the formation of membrane vesicles from the plasma membrane, is an
      essential feature of eukaryotic cell biology. Intense research effort has been
      dedicated to developing methods that can detect endocytosis events with the
      highest resolution. We have classified these methods into four families. They
      exploit the physical properties of endocytosis, namely: 1. Distinguishing
      extracellular from internalised cargo in fixed samples, 2. Monitoring endosomal
      acidification, 3. Measuring the turnover of endocytic zones and 4. Detecting
      vesicle scission. The last three families, all based on fluorescence imaging, are
      used to study endocytosis in living cells. We discuss the advantages and
      limitations of these methods and conclude on the future developments required to
      tackle the upcoming challenges in this fundamental field of cell biology.

PMID- 29056307
TI  - Spinout/Dislocation in Mobile-Bearing Total Knee Arthroplasty: A Report of 26
      Cases.
AB  - BACKGROUND: Excellent medium-term to long-term results for function and
      survivorship have been shown with mobile-bearing (MB) total knee arthroplasty
      (TKA). One of the key arguments against its use is the risk of "spinout" or
      dislocation of the MB. The aim of this study is to discuss the etiology,
      prevention, incidence, management, and outcome of spinout. METHODS: Between
      October 1993 and February 2016, 8373 consecutive primary MB TKAs were performed
      irrespective of preoperative deformity. Before 2001, soft-tissue knee balancing
      was achieved by release of collateral ligaments and all spinouts were treated by
      open reduction. Thereafter, soft-tissue balancing was achieved without ligament
      release and with the use of a higher conformity MB and all spinouts were reduced
      closed, giving 2 comparative cohorts. RESULTS: Twenty-six spinouts occurred in
      8373 (0.31%) patients. In the first cohort up until May 2001, there were 14
      spinouts of 2379 (0.58%) cases. There were 12 in cohort 2, in those patients
      having surgery after May 2001, thus giving an incidence of 12 of 5994 (0.2%),
      which was significantly lower than in cohort 1 (P < .01). Spinout was associated
      with the valgus knee (P < .01) and most (73%) occurred within the first 6 months.
      There was 1 arthrodesis in cohort 1 and 1 both-component revision in cohort 2.
      CONCLUSION: The etiology of spinout is flexion gap instability. It can normally
      be reduced closed with recurrence being uncommon. Focus on soft-tissue balance
      necessary with an MB TKA can reduce the incidence of revision for instability as
      compared to a fixed-bearing TKA. Therefore, the risk of spinout should not be
      used as an argument against the MB TKA.

PMID- 29056308
TI  - Sleep Characteristics in Mothers of Children With Developmental Disabilities.
AB  - Impaired sleep can contribute to conditions such as cardiometabolic disorders,
      depression, and decreased immune function. Mothers of children with developmental
      disabilities (DDs) may be at greater risk for impaired sleep due to the sleep
      problems of their children. This cross-sectional study described the self
      reported sleep characteristics of mothers of children (ages 6-12) with DDs by
      using a sleep diary and the Pittsburgh Sleep Quality Index (PSQI) as quantitative
      and qualitative measures of sleep in these mothers. The Consensus Sleep Diary was
      modified to ascertain how the child's sleep and needs for care during the night
      impacted the mother's sleep. The results showed that mothers had short sleep
      duration (nearly 40% slept <7 hours per night), woke up an average of 2.2 times
      per night (most commonly due to caregiving needs of children), and had poor sleep
      quality (mean PSQI global score of 7.9 [SD=4.8]). The sleep problems of children
      with DDs may influence mothers' sleep.

PMID- 29056309
TI  - Sensitive Timing for Risk of Overweight Among Infants of Low-Income Hispanic
      Immigrants.
AB  - INTRODUCTION: This study examined the association between early weight gain (0-6
      months) and risk for overweight, as defined by the Institute of Medicine, at 1
      year among infants of low-income Hispanic immigrant mothers. METHOD: Weight-for
      age data were extracted from electronic medical records of 335 infants with
      gestations of 37 weeks or longer and birthweights appropriate for gestational age
      and without medical problems likely to interfere with growth or feeding. Logistic
      regression models were constructed to examine the impact of early weight changes
      on weight status at 1 year. RESULTS: By 12 months, 36.7% of infants had crossed
      weight-for-age of 84.1% or greater on World Health Organization growth charts. In
      adjusted models, infants had 20.8 (95% confidence interval = [19.8, 44.0]) times
      the odds of reaching this benchmark at 1 year for each z score increase at 0 to 6
      months. DISCUSSION: The study highlights a time-sensitive opportunity for
      interventions to reduce risk for overweight for this vulnerable population.

PMID- 29056310
TI  - Breastfeeding Outcomes in Washington State: Determining the Effect of Loving
      Support Peer Counseling Program and Characteristics of Participants at WIC
      Agencies.
AB  - OBJECTIVE: Determining the effect of the Loving Support Peer Counseling Program
      (LSPCP), and characteristics of participants on breastfeeding (BF) outcomes at
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      agencies in Washington State. DESIGN: Nonrandomized treatment vs control.
      SETTING: Public Health-Seattle and King County (PHSKC), Catholic Health
      Initiatives Franciscan Medical Group (CHIFMG). PARTICIPANTS: Women enrolled in
      WIC (intervention: PHSKC, n = 15,290; CHIFMG, n = 3,582). INTERVENTIONS: Clinics
      with a LSPCP. MAIN OUTCOME MEASURES: BF initiation and BF duration of all infants
      who turned 8 months old during the reported period. ANALYSIS: Two-tailed binomial
      test and tree-based regression. RESULTS: Both PHSKC and CHIFMG clinics with a
      LSPCP expressed significant (P < .001) improvement in BF initiation and BF
      duration for >6 months. The likelihood that women enrolled in WIC would initiate
      BF at PHSKC clinics increased by 3%, whereas those in CHIFMG clinics increased by
      6.8%. Women receiving services in smaller PHSKC clinics (n < 60 women) were
      likely to breastfeed their infants at >1 week. The proportionalities of non
      Hispanic and black participants in PHSKC clinics were the primary and secondary
      predictors of the likelihood of BF discontinuing between 7 and 28 days' duration.
      In addition, clinics serving participants who spoke Tigrigna had increased rates
      of BF for a minimum of 6 months. CONCLUSIONS AND IMPLICATIONS: Findings may be
      used to reevaluate funding allocations, secure grants to reduce program
      constraints to stabilize LSPCP, develop strategies to reduce BF cessation at
      larger clinics, and improve peer counseling and other BF support to black and non
      Hispanic women in the early postpartum period. The findings contribute to the
      study of the effects of LSPCP on BF initiation and duration while furthering a
      scholarly understanding of the way in which the WIC program interacts with
      participant characteristics at 2 local WIC agencies in Washington State.

PMID- 29056311
TI  - An international prospective cohort study of mobile phone users and health
      (COSMOS): Factors affecting validity of self-reported mobile phone use.
AB  - This study investigates validity of self-reported mobile phone use in a subset of
      75 993 adults from the COSMOS cohort study. Agreement between self-reported and
      operator-derived mobile call frequency and duration for a 3-month period was
      assessed using Cohen's weighted Kappa (kappa). Sensitivity and specificity of
      both self-reported high (>=10 calls/day or >=4h/week) and low (<=6 calls/week or
      <30min/week) mobile phone use were calculated, as compared to operator data. For
      users of one mobile phone, agreement was fair for call frequency (kappa=0.35, 95%
      CI: 0.35, 0.36) and moderate for call duration (kappa=0.50, 95% CI: 0.49, 0.50).
      Self-reported low call frequency and duration demonstrated high sensitivity (87%
      and 76% respectively), but for high call frequency and duration sensitivity was
      lower (38% and 56% respectively), reflecting a tendency for greater
      underestimation than overestimation. Validity of self-reported mobile phone use
      was lower in women, younger age groups and those reporting symptoms
      during/shortly after using a mobile phone. This study highlights the ongoing
      value of using self-report data to measure mobile phone use. Furthermore,
      compared to continuous scale estimates used by previous studies, categorical
      response options used in COSMOS appear to improve validity considerably, most
      likely by preventing unrealistically high estimates from being reported.

PMID- 29056312
TI  - Bone Geometric Properties of the Femoral Neck in Underweight Eumenorrheic Women.
AB  - The aim of this study was to describe femoral neck (FN) geometry among
      eumenorrheic underweight women around the age of peak bone mass. Proximal femur
      geometry and body composition were assessed in 12 underweight women and in 24
      healthy controls using dual-energy X-ray absorptiometry. The Hip Structural
      Analysis program was used to determine bone geometry at the FN. The cross
      sectional area (CSA) and the cross-sectional moment of inertia (CSMI) were
      significantly lower in underweight women than in controls (p < 0.05). There was a
      trend toward lower sectional modulus (Z) and strength index in underweight women
      (p < 0.15). Body weight, body mass index, and lean mass (LM) were positively
      correlated with CSA, CSMI, Z, and neck-shaft angle (r = 0.428-0.611, p < 0.05).
      After controlling for body weight, body mass index, and LM, the differences in
      CSA, CSMI, Z, and neck-shaft angle were no more statistically significant between
      the 2 groups. The multivariate analysis retained LM as the main predictor of CSA,
      CSMI, and Z in the whole population. The present study suggests that thinness is
      associated with low resistance to axial forces (CSA) and bending load (Z and
      CSMI) in adult eumenorrheic women. LM seems to be a key determinant of FN
      geometry in underweight women.

PMID- 29056313
TI  - Vocal Changes Following Thyroid Surgery: Prospective Study of Objective and
      Subjective Parameters.
AB  - OBJECTIVE: Vocal changes are frequent following a surgical procedure to the
      thyroid gland. Even though they are a recognized morbidity, their bases are yet
      to be defined as well as their effect on vocal parameters. This study
      investigates the objective and subjective changes that occur after the surgery.
      STUDY DESIGN: This study is a prospective analysis of consecutive cases. SETTING:
      This study was conducted in a single-center tertiary care facility. SUBJECTS AND
      METHODS: Patients programmed for any thyroid procedure in Hospital Universitario
      Ramon y Cajal were enrolled consecutively to perform the vocal analysis before
      and after the surgery from April 2014 to April 2016. Patients were divided
      according to the vocal fold motility, and their vocal and aerodynamic parameters
      were obtained by means of electroglottography and phonatory aerodynamic system.
      Patients filled in the 10-item Voice Handicap Index (VHI-10) questionnaire.
      Statistical analysis was performed comparing vocal and aerodynamic parameters and
      quality of life before and after the surgery. RESULTS: 218 patients met inclusion
      criteria and completed the protocol. A total of 86.6% of the sample showed no
      vocal motility impairment, whereas the rest of the patients showed a paresis or a
      paralysis. Maximum phonatory time and VHI-10 questionnaire showed a statistically
      significant difference (P < 0.05) between groups. No differences were assessed
      regarding other vocal parameters. CONCLUSIONS: Efforts are still needed to
      understand the groundings and magnitude of the vocal changes after a thyroid
      surgery.

PMID- 29056314
TI  - Surgeon Variation in Intraoperative Supply Cost for Pancreaticoduodenectomy: Is
      Intraoperative Supply Cost Associated with Outcomes?
AB  - BACKGROUND: With increased scrutiny on the quality and cost of health care,
      surgeons must be mindful of their outcomes and resource use. We evaluated surgeon
      specific intraoperative supply cost (ISC) for pancreaticoduodenectomy and
      examined whether ISC was associated with patient outcomes. STUDY DESIGN: Patients
      undergoing open pancreaticoduodenectomy between January 2012 and March 2015 were
      included. Outcomes were tracked prospectively through postoperative day 90, and
      ISC was defined as the facility cost of single-use surgical items and
      instruments, plus facility charges for multiuse equipment. Multivariate logistic
      regression was used to test associations between ISC and patient outcomes using
      repeated measures at the surgeon level. RESULTS: There were 249 patients who met
      inclusion criteria. Median ISC was $1,882 (interquartile range [IQR] $1,497 to
      $2,281). Case volume for 6 surgeons ranged from 18 to 66. Median surgeon-specific
      ISC ranged from $1,496 to $2,371. Greater case volume was associated with
      decreased ISC (p < 0.001). Overall, ISC was not predictive of postoperative
      complications (p = 0.702) or total hospitalization expenditures (p = 0.195). At
      the surgeon level, surgeon-specific ISC was not associated with the surgeon
      specific incidence of severe complication or any wound infection (p > 0.227 for
      both), but was associated with delayed gastric emptying (p = 0.004) and
      postoperative pancreatic fistula (p < 0.001). CONCLUSIONS: In a single
      institution cohort of 249 pancreaticoduodenectomies, high-volume surgeons tended
      to be low-cost surgeons. Across the cohort, ISC was not associated with outcomes.
      At the surgeon level, associations were noted between ISC and complications, but
      these may be attributable to unmeasured differences in the postoperative
      management of patients. These findings suggest that quality improvement efforts
      to restructure resource use toward more cost-effective practice may not affect
      patient outcomes, although prospective monitoring of safety and effectiveness
      must be of the utmost concern.

PMID- 29056315
TI  - Diet quality and bullying among a cross-national sample of youth.
AB  - Bullying perpetration and victimization have been linked to a number of high-risk
      health behaviors, including involvement in sedentary activities and sleep
      deprivation. Even so, the link between diet quality and bullying is generally
      overlooked. The present study examines the associations between diet quality,
      bully perpetration, and bully victimization in a cross-national sample of
      adolescents. Data come from the Health Behaviors of School Children (HBSC)
      survey, 2005/2006 (N=142,828-143,425). Youths from 41 countries/regions in North
      America and Europe reported features of their social context, various health
      behaviors, and their involvement in bullying. Approximately 11% of youth in the
      sample bully other youths at least 2-3 times a month, whereas 13% of youth are
      bullied by other youths at least 2-3 times a month. Logistic regression analyses
      revealed that youths with low quality diets incurred a 123% increase in the odds
      of attaining bully status, relative to youths with high quality diets. No such
      association was detected between diet quality and victim status. Results also
      suggest that the association between low diet quality and bully perpetration is
      significantly more pronounced in very developed nations (relative to developed
      nations). Dietary behaviors may be an important point of intervention in the
      effort to minimize the prevalence of bullying among youths, particularly in very
      developed nations. Scholars should seek to build upon the current study by
      exploring the mechanisms (e.g., low self-control) that might explain the
      association between diet quality and bullying.

PMID- 29056316
TI  - Consumptive behavior, eating behavior, and antisocial behavior: The ubiquitous
      roles of self-control.

PMID- 29056317
TI  - Men who have sex with men and women (MSMW), biphobia and the CDC: A bridge
      ignored?!
AB  - This is a letter to the editor on a Short Communication by a group of CDC
      researchers. It speaks of the importance of bisexual behavior in the transmission
      of HIV to heterosexual females. In this letter, I demonstrate that the
      differences between MSM only and MSMW have been discussed by CDC researchers and
      CDC collaborative researchers previously, although the CDC continues to maintain
      its original risk category classification, which undermines the role of bisexuals
      in HIV transmission to heterosexual females. In the CDC risk category
      classification where men who have sex with men and women (MSMW) are subsumed
      under the MSM category, it is impossible to know the extent of HIV transmission
      from MSMW to heterosexual women. Since more Blacks and Hispanics admit to
      bisexual behavior, the original CDC risk category classification has had a more
      serious adverse impact on minority communities. I argue that the CDC should
      change its risk category classification to include MSM only and MSMW as well as
      women who have sex with men only (WSM) and women who have sex with men and women
      (WSMW), even at this late stage.

PMID- 29056318
TI  - Jeffries et al. respond to "Men who have sex with men and women (MSMW), biphobia
      and the CDC: A bridge ignored!?"

PMID- 29056319
TI  - Primary HPV testing recommendations of US providers, 2015.
AB  - OBJECTIVE: To investigate the HPV testing recommendations of US physicians who
      perform cervical cancer screening. METHODS: Data from the 2015 DocStyles survey
      of U.S. health care providers were analyzed using multivariate logistic
      regression to identify provider characteristics associated with routine
      recommendation of primary HPV testing for average-risk, asymptomatic women
      >=30years old. The analysis was limited to primary care physicians and
      obstetrician-gynecologists who performed cervical cancer screening (N=843).
      RESULTS: Primary HPV testing for average-risk, asymptomatic women >=30years old
      was recommended by 40.8% of physicians who performed cervical cancer screening,
      and 90.1% of these providers recommended primary HPV testing for women of all
      ages. The screening intervals most commonly recommended for primary HPV testing
      with average-risk, asymptomatic women >=30years old were every 3years (35.5%) and
      annually (30.2%). Physicians who reported that patient HPV vaccination status
      influenced their cervical cancer screening practices were almost four times more
      likely to recommend primary HPV testing for average-risk, asymptomatic women
      >=30years old than other providers (Adj OR=3.96, 95% CI=2.82-5.57). CONCLUSION:
      Many US physicians recommended primary HPV testing for women of all ages,
      contrary to guidelines which limit this screening approach to women >=25years
      old. The association between provider recommendation of primary HPV testing and
      patient HPV vaccination status may be due to anticipated reductions in the most
      oncogenic HPV types among vaccinated women.

PMID- 29056320
TI  - Effective use of human papillomavirus testing for cervical cancer screening
      requires extended intervals to target persistent infections and precancerous
      lesions.
AB  - Invited editorial for PM 17 348R2, a CDC survey regarding primary HPV testing.

PMID- 29056321
TI  - CBP Regulates Recruitment and Release of Promoter-Proximal RNA Polymerase II.
AB  - Transcription activation involves RNA polymerase II (Pol II) recruitment and
      release from the promoter into productive elongation, but how specific chromatin
      regulators control these steps is unclear. Here, we identify a novel activity of
      the histone acetyltransferase p300/CREB-binding protein (CBP) in regulating
      promoter-proximal paused Pol II. We find that Drosophila CBP inhibition results
      in "dribbling" of Pol II from the pause site to positions further downstream but
      impedes transcription through the +1 nucleosome genome-wide. Promoters strongly
      occupied by CBP and GAGA factor have high levels of paused Pol II, a unique
      chromatin signature, and are highly expressed regardless of cell type.
      Interestingly, CBP activity is rate limiting for Pol II recruitment to these
      highly paused promoters through an interaction with TFIIB but for transit into
      elongation by histone acetylation at other genes. Thus, CBP directly stimulates
      both Pol II recruitment and the ability to traverse the first nucleosome, thereby
      promoting transcription of most genes.

PMID- 29056322
TI  - Intersubunit Crosstalk in the Rag GTPase Heterodimer Enables mTORC1 to Respond
      Rapidly to Amino Acid Availability.
AB  - mTOR complex I (mTORC1) is a central growth regulator that senses amino acids
      through a pathway that converges on the Rag GTPases, an obligate heterodimer of
      two related GTPases. Despite their central role in amino acid sensing, it is
      unknown why the Rag GTPases are heterodimeric and whether their subunits
      communicate with each other. Here, we find that the binding of guanosine
      triphosphate (GTP) to one subunit inhibits the binding and induces the hydrolysis
      of GTP by the other. This intersubunit communication pushes the Rag GTPases into
      either of two stable configurations, which represent active "on" or "off" states
      that interconvert via transient intermediates. Subunit coupling confers on the
      mTORC1 pathway its capacity to respond rapidly to the amino acid level. Thus, the
      dynamic response of mTORC1 requires intersubunit communication by the Rag
      GTPases, providing a rationale for why they exist as a dimer and revealing a
      distinct mode of control for a GTP-binding protein.

PMID- 29056323
TI  - Impeding Transcription of Expanded Microsatellite Repeats by Deactivated Cas9.
AB  - Transcription of expanded microsatellite repeats is associated with multiple
      human diseases, including myotonic dystrophy, Fuchs endothelial corneal
      dystrophy, and C9orf72-ALS/FTD. Reducing production of RNA and proteins arising
      from these expanded loci holds therapeutic benefit. Here, we tested the
      hypothesis that deactivated Cas9 enzyme impedes transcription across expanded
      microsatellites. We observed a repeat length-, PAM-, and strand-dependent
      reduction of repeat-containing RNAs upon targeting dCas9 directly to repeat
      sequences; targeting the non-template strand was more effective. Aberrant
      splicing patterns were rescued in DM1 cells, and production of RAN peptides
      characteristic of DM1, DM2, and C9orf72-ALS/FTD cells was drastically decreased.
      Systemic delivery of dCas9/gRNA by adeno-associated virus led to reductions in
      pathological RNA foci, rescue of chloride channel 1 protein expression, and
      decreased myotonia. These observations suggest that transcription of
      microsatellite repeat-containing RNAs is more sensitive to perturbation than
      transcription of other RNAs, indicating potentially viable strategies for
      therapeutic intervention.

PMID- 29056324
TI  - The Dynamics of mRNA Turnover Revealed by Single-Molecule Imaging in Single
      Cells.
AB  - RNA degradation plays a fundamental role in regulating gene expression. In order
      to characterize the spatiotemporal dynamics of RNA turnover in single cells, we
      developed a fluorescent biosensor based on dual-color, single-molecule RNA
      imaging that allows intact transcripts to be distinguished from stabilized
      degradation intermediates. Using this method, we measured mRNA decay in single
      cells and found that individual degradation events occur independently within the
      cytosol and are not enriched within processing bodies. We show that slicing of an
      mRNA targeted for endonucleolytic cleavage by the RNA-induced silencing complex
      can be observed in real time in living cells. This methodology provides a
      framework for investigating the entire life history of individual mRNAs from
      birth to death in single cells.

PMID- 29056326
TI  - Association of visitation policy and health care-acquired respiratory viral
      infections in hospitalized children.
AB  - Visitor restriction policies are meant to prevent health care-acquired viral
      infections; however, data on their efficacy in hospitalized children are limited.
      We report a 37% reduction in health care-acquired respiratory viral infections in
      a children's hospital following standardization of the visitation policy that
      limited the number of visitors during a patient's hospitalization.

PMID- 29056325
TI  - PTEN Regulates PI(3,4)P2 Signaling Downstream of Class I PI3K.
AB  - The PI3K signaling pathway regulates cell growth and movement and is heavily
      mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3.
      PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing
      PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a
      PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that
      PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN
      is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B,
      a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2,
      which correlated with increased invadopodia in epidermal growth factor (EGF)
      stimulated cells. PTEN deletion increased PI(3,4)P2 levels in a mouse model of
      prostate cancer, and it inversely correlated with PI(3,4)P2 levels across several
      EGF-stimulated prostate and breast cancer lines. These results point to a role
      for PI(3,4)P2 in the phenotype caused by loss-of-function mutations or deletions
      in PTEN.

PMID- 29056327
TI  - Impact of home versus hospital dressing on bacterial contamination of surgical
      scrubs in the obstetric setting: A randomized controlled trial.
AB  - BACKGROUND: The impact of the site where an obstetrician dresses in their
      surgical scrubs, home versus hospital, on total bacterial burden remains unknown.
      Therefore, our objective was to quantify the effect of dressing in surgical
      scrubs at home versus at the hospital on the bacterial contamination at the
      beginning of a scheduled shift. METHODS: This was a single blind randomized
      controlled trial. Eligible participants were resident physicians assigned to
      labor and delivery at a single institution during the study period, and
      participants were randomized daily to 1 of 4 arms based on the site where their
      scrubs were laundered (A) and where the resident dressed (B) (A/B): home/home,
      home/hospital, hospital/home, and hospital/hospital. At the beginning of the
      assigned shift, microbiologic samples from the chest pocket and pants' tie were
      collected with a sterile culture swab. Samples were plated on trypticase soy agar
      with 5% sheep blood before being incubated at 35 degrees C-37 degrees C for 48
      hours, with observation every 24 hours. The primary outcome was total bacterial
      burden, defined as the sum of the colony forming units (CFUs) from the 2 sampling
      sites. RESULTS: There were 21 residents randomized daily for 4 days to 1 of 4
      study arms, resulting in 84 observations. There were no baseline differences
      between the home- and hospital-dressed cohorts. Overall, 68% of sampled scrubs
      demonstrated some bacterial growth. There was no difference between the home- and
      hospital-dressed cohorts in percentage of samples demonstrating any bacterial
      growth after 72 hours (60% vs 76%, P = .14), nor in median bacterial burden at
      the beginning of a shift (2 [interquartile range, 0-7] vs 1 [interquartile range,
      1-5] CFUs, P = .62). Finally, there was no difference in total bacterial burden
      at the beginning of a shift between the home- and hospital-dressed cohorts when
      stratified by site where the scrubs were laundered. CONCLUSIONS: There was no
      significant difference in total bacterial burden of surgical scrubs at the start
      of a shift between cohorts who dressed at home versus at the hospital.

PMID- 29056328
TI  - Controlling for endogeneity in attributable costs of vancomycin-resistant
      enterococci from a Canadian hospital.
AB  - BACKGROUND: Decisions regarding the optimal provision of infection prevention and
      control resources depend on accurate estimates of the attributable costs of
      health care-associated infections. This is challenging given the skewed nature of
      health care cost data and the endogeneity of health care-associated infections.
      The objective of this study is to determine the hospital costs attributable to
      vancomycin-resistant enterococci (VRE) while accounting for endogeneity. METHODS:
      This study builds on an attributable cost model conducted by a retrospective
      cohort study including 1,292 patients admitted to an urban hospital in Vancouver,
      Canada. Attributable hospital costs were estimated with multivariate generalized
      linear models (GLMs). To account for endogeneity, a control function approach was
      used. RESULTS: The analysis sample included 217 patients with health care
      associated VRE. In the standard GLM, the costs attributable to VRE are $17,949
      (SEM, $2,993). However, accounting for endogeneity, the attributable costs were
      estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across
      all model specifications, attributable costs are 76% higher on average when
      controlling for endogeneity. CONCLUSIONS: VRE was independently associated with
      increased hospital costs, and controlling for endogeneity lead to higher
      attributable cost estimates.

PMID- 29056329
TI  - Patient and health care worker perceptions of daily use of ultraviolet-C
      technology as an adjunct to daily cleaning in an academic hospital: Secondary
      study of Ultra Violet-C Light Evaluation as an Adjunct to Removing Multi-Drug
      Resistant Organisms.
AB  - A cluster randomized crossover trial is in progress at The Johns Hopkins Hospital
      to investigate the impact of daily ultraviolet (UV)-C light disinfection on the
      acquisition of health care-associated pathogens. To understand perceptions and
      challenges to daily use of UV-C, we surveyed health care workers (HCWs) and
      patients. Most HCWs think daily UV-C decreases the patients' risk of acquiring
      infection. Daily UV-C is acceptable to patients and may enhance their overall
      hospital experience.

PMID- 29056330
TI  - Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced
      Pluripotent Stem Cell Differentiation into Osteoclasts.
AB  - We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an
      easy-to-use protocol for differentiating osteoclasts from human induced
      pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder,
      characterized by life-long progressive thickening of craniofacial bones and
      abnormal shape of long bones. hiPSCs from CMD patients with an in-frame deletion
      of Phe377 or Ser375 in ANKH are more refractory to in vitro osteoclast
      differentiation than control hiPSCs. To exclude differentiation effects due to
      genetic variability, we generated isogenic hiPSCs, which have identical genetic
      background except for the ANKH mutation. Isogenic hiPSCs with ANKH mutations
      formed fewer osteoclasts, resorbed less bone, expressed lower levels of
      osteoclast marker genes, and showed decreased protein levels of ANKH and vacuolar
      proton pump v-ATP6v0d2. This proof-of-concept study demonstrates that efficient
      and reproducible differentiation of isogenic hiPSCs into osteoclasts is possible
      and a promising tool for investigating mechanisms of CMD or other osteoclast
      related disorders.

PMID- 29056331
TI  - Alkaline Ceramidase 1 Protects Mice from Premature Hair Loss by Maintaining the
      Homeostasis of Hair Follicle Stem Cells.
AB  - Ceramides and their metabolites are important for the homeostasis of the
      epidermis, but much remains unknown about the roles of specific pathways of
      ceramide metabolism in skin biology. With a mouse model deficient in the alkaline
      ceramidase (Acer1) gene, we demonstrate that ACER1 plays a key role in the
      homeostasis of the epidermis and its appendages by controlling the metabolism of
      ceramides. Loss of Acer1 elevated the levels of various ceramides and sphingoid
      bases in the skin and caused progressive hair loss in mice. Mechanistic studies
      revealed that loss of Acer1 widened follicular infundibulum and caused
      progressive loss of hair follicle stem cells (HFSCs) due to reduced survival and
      stemness. These results suggest that ACER1 plays a key role in maintaining the
      homeostasis of HFSCs, and thereby the hair follicle structure and function, by
      regulating the metabolism of ceramides in the epidermis.

PMID- 29056332
TI  - Mouse Genetic Analysis of Bone Marrow Stem Cell Niches: Technological Pitfalls,
      Challenges, and Translational Considerations.
AB  - The development of mouse genetic tools has made a significant contribution to the
      understanding of skeletal and hematopoietic stem cell niches in bone marrow (BM).
      However, many experimental designs (e.g., selections of marker genes, target
      vector constructions, and choices of reporter murine strains) have unavoidable
      technological limitations and bias, which lead to experimental discrepancies,
      data reproducibility issues, and frequent data misinterpretation. Consequently,
      there are a number of conflicting views relating to fundamental biological
      questions, including origins and locations of skeletal and hematopoietic stem
      cells in the BM. In this report, we systematically unravel complicated data
      interpretations via comprehensive analyses of technological benefits, pitfalls,
      and challenges in frequently used mouse models and discuss their translational
      relevance to human stem cell biology. Particularly, we emphasize the important
      roles of using large human genomic data-informatics in facilitating genetic
      analyses of mouse models and resolving existing controversies in mouse and human
      BM stem cell biology.

PMID- 29056333
TI  - The Spindle Assembly Checkpoint Is Required for Hematopoietic Progenitor Cell
      Engraftment.
AB  - The spindle assembly checkpoint plays a pivotal role in preventing aneuploidy and
      transformation. Many studies demonstrate impairment of this checkpoint in cancer
      cells. While leukemia is frequently driven by transformed hematopoietic stem and
      progenitor cells (HSPCs), the biology of the spindle assembly checkpoint in such
      primary cells is not very well understood. Here, we reveal that the checkpoint is
      fully functional in murine progenitor cells and, to a lesser extent, in
      hematopoietic stem cells. We show that HSPCs arrest at prometaphase and induce
      p53-dependent apoptosis upon prolonged treatment with anti-mitotic drugs.
      Moreover, the checkpoint can be chemically and genetically abrogated, leading to
      premature exit from mitosis, subsequent enforced G1 arrest, and enhanced levels
      of chromosomal damage. We finally demonstrate that, upon checkpoint abrogation in
      HSPCs, hematopoiesis is impaired, manifested by loss of differentiation potential
      and engraftment ability, indicating a critical role of this checkpoint in HSPCs
      and hematopoiesis.

PMID- 29056334
TI  - Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of
      Heterogeneous Identities in Embryonic Stem Cells.
AB  - Embryonic stem cells (ESCs) cultured in leukemia inhibitory factor (LIF) plus
      fetal bovine serum (FBS) exhibit heterogeneity in the expression of naive and
      primed transcription factors. This heterogeneity reflects the dynamic condition
      of ESCs and their versatility to promptly respond to signaling effectors
      promoting naive or primed pluripotency. Here, we report that ESCs lacking Nanog
      or overexpressing Otx2 exhibit an early primed identity in LIF + FBS and fail to
      convert into 2i-induced naive state. Conversely, Otx2-null ESCs possess naive
      identity features in LIF + FBS similar to Nanog-overexpressing ESCs and convert
      poorly into FGF-induced early primed state. When both Nanog and Otx2 are
      inactivated, ESCs cultured in LIF + FBS exhibit primed identity and weakened
      ability to convert into naive state. These data suggest that, through mutual
      antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs cultured in
      LIF + FBS and individually predispose them for optimal response to naive or
      primed inducing factors.

PMID- 29056335
TI  - Laser Capture and Deep Sequencing Reveals the Transcriptomic Programmes
      Regulating the Onset of Pancreas and Liver Differentiation in Human Embryos.
AB  - To interrogate the alternative fates of pancreas and liver in the earliest stages
      of human organogenesis, we developed laser capture, RNA amplification, and
      computational analysis of deep sequencing. Pancreas-enriched gene expression was
      less conserved between human and mouse than for liver. The dorsal pancreatic bud
      was enriched for components of Notch, Wnt, BMP, and FGF signaling, almost all
      genes known to cause pancreatic agenesis or hypoplasia, and over 30 unexplored
      transcription factors. SOX9 and RORA were imputed as key regulators in pancreas
      compared with EP300, HNF4A, and FOXA family members in liver. Analyses implied
      that current in vitro human stem cell differentiation follows a dorsal rather
      than a ventral pancreatic program and pointed to additional factors for hepatic
      differentiation. In summary, we provide the transcriptional codes regulating the
      start of human liver and pancreas development to facilitate stem cell research
      and clinical interpretation without inter-species extrapolation.

PMID- 29056336
TI  - The impact of age and comorbidities on practice patterns and outcomes in patients
      with relapsed/refractory multiple myeloma in the era of novel therapies.
AB  - OBJECTIVES: One-third of patients with multiple myeloma (MM) are diagnosed at
      age>=75years. Older patients have increased incidence of cardiovascular disease
      (CVD) and renal insufficiency (RI), hallmark complications of MM. We examined
      cumulative incidence of CVD and RI in relapsed/refractory MM (RRMM) and outcomes
      by age and RI/CVD. MATERIALS AND METHODS: Retrospective cohort study using a
      large US electronic medical records database of adult patients with RRMM
      initiating first- and second-line therapy (2LT) between 1/2008-06/2015. RI and
      CVD comorbidities were based on diagnosis codes and/or lab values. RESULTS: Among
      628 patients, 37.1% were >=75years. Cumulative incidence of CVD and/or RI
      increased from 47.7% at MM diagnosis to 67.8% at first relapse. Age>=75years had
      a trend toward higher risk of relapse post 2LT, proxied by time to next treatment
      (TTNT), (adjusted HR: 1.28; 95% CI: 1.00, 1.65; P=0.05). TTNT was significantly
      higher with comorbid CVD+RI (adjusted HR: 1.50; 95% CI: 1.11, 2.02; P<0.01).
      Age>=75years, RI, CVD, and CVD+RI were associated with increased mortality risk
      from 2LT initiation; adjusted HR: 1.66 (95% CI: 1.19, 2.33; P<0.01), 1.51 (95%
      CI: 1.01, 2.26; P=0.04), 1.75 (95% CI: 1.03, 2.96; P=0.04), and 1.95 (95% CI:
      1.29, 2.93; P<0.01), respectively. CONCLUSION: Despite treatment with novel
      agents for RRMM in 86% of patients, an outcome gap persists for older patients
      and those with RI and/or CVD. Personalized treatment approaches that account for
      age and comorbidities, and further evaluation of innovative regimens and dosing
      schedules, are needed to improve outcomes for these patients.

PMID- 29056337
TI  - Early-Life Gene Expression in Neurons Modulates Lasting Epigenetic States.
AB  - In mammals, the environment plays a critical role in promoting the final steps in
      neuronal development during the early postnatal period. While epigenetic factors
      are thought to contribute to this process, the underlying molecular mechanisms
      remain poorly understood. Here, we show that in the brain during early life, the
      DNA methyltransferase DNMT3A transiently binds across transcribed regions of
      lowly expressed genes, and its binding specifies the pattern of DNA methylation
      at CA sequences (mCA) within these genes. We find that DNMT3A occupancy and mCA
      deposition within the transcribed regions of genes is negatively regulated by
      gene transcription and may be modified by early-life experience. Once deposited,
      mCA is bound by the methyl-DNA-binding protein MECP2 and functions in a rheostat
      like manner to fine-tune the cell-type-specific transcription of genes that are
      critical for brain function.

PMID- 29056338
TI  - Selective Inhibition of FOXO1 Activator/Repressor Balance Modulates Hepatic
      Glucose Handling.
AB  - Insulin resistance is a hallmark of diabetes and an unmet clinical need. Insulin
      inhibits hepatic glucose production and promotes lipogenesis by suppressing FOXO1
      dependent activation of G6pase and inhibition of glucokinase, respectively. The
      tight coupling of these events poses a dual conundrum: mechanistically, as the
      FOXO1 corepressor of glucokinase is unknown, and clinically, as inhibition of
      glucose production is predicted to increase lipogenesis. Here, we report that
      SIN3A is the insulin-sensitive FOXO1 corepressor of glucokinase. Genetic ablation
      of SIN3A abolishes nutrient regulation of glucokinase without affecting other
      FOXO1 target genes and lowers glycemia without concurrent steatosis. To extend
      this work, we executed a small-molecule screen and discovered selective
      inhibitors of FOXO-dependent glucose production devoid of lipogenic activity in
      hepatocytes. In addition to identifying a novel mode of insulin action, these
      data raise the possibility of developing selective modulators of unliganded
      transcription factors to dial out adverse effects of insulin sensitizers.

PMID- 29056339
TI  - Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance.
AB  - Laboratory mice, while paramount for understanding basic biological phenomena,
      are limited in modeling complex diseases of humans and other free-living mammals.
      Because the microbiome is a major factor in mammalian physiology, we aimed to
      identify a naturally evolved reference microbiome to better recapitulate
      physiological phenomena relevant in the natural world outside the laboratory.
      Among 21 distinct mouse populations worldwide, we identified a closely related
      wild relative to standard laboratory mouse strains. Its bacterial gut microbiome
      differed significantly from its laboratory mouse counterpart and was transferred
      to and maintained in laboratory mice over several generations. Laboratory mice
      reconstituted with natural microbiota exhibited reduced inflammation and
      increased survival following influenza virus infection and improved resistance
      against mutagen/inflammation-induced colorectal tumorigenesis. By demonstrating
      the host fitness-promoting traits of natural microbiota, our findings should
      enable the discovery of protective mechanisms relevant in the natural world and
      improve the modeling of complex diseases of free-living mammals. VIDEO ABSTRACT.

PMID- 29056340
TI  - STING Senses Microbial Viability to Orchestrate Stress-Mediated Autophagy of the
      Endoplasmic Reticulum.
AB  - Constitutive cell-autonomous immunity in metazoans predates interferon-inducible
      immunity and comprises primordial innate defense. Phagocytes mobilize interferon
      inducible responses upon engagement of well-characterized signaling pathways by
      pathogen-associated molecular patterns (PAMPs). The signals controlling
      deployment of constitutive cell-autonomous responses during infection have
      remained elusive. Vita-PAMPs denote microbial viability, signaling the danger of
      cellular exploitation by intracellular pathogens. We show that cyclic-di
      adenosine monophosphate in live Gram-positive bacteria is a vita-PAMP, engaging
      the innate sensor stimulator of interferon genes (STING) to mediate endoplasmic
      reticulum (ER) stress. Subsequent inactivation of the mechanistic target of
      rapamycin mobilizes autophagy, which sequesters stressed ER membranes, resolves
      ER stress, and curtails phagocyte death. This vita-PAMP-induced ER-phagy
      additionally orchestrates an interferon response by localizing ER-resident STING
      to autophagosomes. Our findings identify stress-mediated ER-phagy as a cell
      autonomous response mobilized by STING-dependent sensing of a specific vita-PAMP
      and elucidate how innate receptors engage multilayered homeostatic mechanisms to
      promote immunity and survival after infection.

PMID- 29056341
TI  - The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12.
AB  - CLYBL encodes a ubiquitously expressed mitochondrial enzyme, conserved across all
      vertebrates, whose cellular activity and pathway assignment are unknown. Its
      homozygous loss is tolerated in seemingly healthy individuals, with reduced
      circulating B12 levels being the only and consistent phenotype reported to date.
      Here, by combining enzymology, structural biology, and activity-based
      metabolomics, we report that CLYBL operates as a citramalyl-CoA lyase in
      mammalian cells. Cells lacking CLYBL accumulate citramalyl-CoA, an intermediate
      in the C5-dicarboxylate metabolic pathway that includes itaconate, a recently
      identified human anti-microbial metabolite and immunomodulator. We report that
      CLYBL loss leads to a cell-autonomous defect in the mitochondrial B12 metabolism
      and that itaconyl-CoA is a cofactor-inactivating, substrate-analog inhibitor of
      the mitochondrial B12-dependent methylmalonyl-CoA mutase (MUT). Our work de
      orphans the function of human CLYBL and reveals that a consequence of exposure to
      the immunomodulatory metabolite itaconate is B12 inactivation.

PMID- 29056342
TI  - Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy.
AB  - Despite its success in several clinical trials, cancer immunotherapy remains
      limited by the rarity of targetable tumor-specific antigens, tumor-mediated
      immune suppression, and toxicity triggered by systemic delivery of potent
      immunomodulators. Here, we present a proof-of-concept immunomodulatory gene
      circuit platform that enables tumor-specific expression of immunostimulators,
      which could potentially overcome these limitations. Our design comprised de novo
      synthetic cancer-specific promoters and, to enhance specificity, an RNA-based AND
      gate that generates combinatorial immunomodulatory outputs only when both
      promoters are mutually active. These outputs included an immunogenic cell-surface
      protein, a cytokine, a chemokine, and a checkpoint inhibitor antibody. The
      circuits triggered selective T cell-mediated killing of cancer cells, but not of
      normal cells, in vitro. In in vivo efficacy assays, lentiviral circuit delivery
      mediated significant tumor reduction and prolonged mouse survival. Our design
      could be adapted to drive additional immunomodulators, sense other cancers, and
      potentially treat other diseases that require precise immunological programming.

PMID- 29056343
TI  - ILC1 Confer Early Host Protection at Initial Sites of Viral Infection.
AB  - Infection is restrained by the concerted activation of tissue-resident and
      circulating immune cells. Whether tissue-resident lymphocytes confer early
      antiviral immunity at local sites of primary infection prior to the initiation of
      circulating responses is not well understood. Furthermore, the kinetics of
      initial antiviral responses at sites of infection remain unclear. Here, we show
      that tissue-resident type 1 innate lymphoid cells (ILC1) serve an essential early
      role in host immunity through rapid production of interferon (IFN)-gamma
      following viral infection. Ablation of Zfp683-dependent liver ILC1 lead to
      increased viral load in the presence of intact adaptive and innate immune cells
      critical for mouse cytomegalovirus (MCMV) clearance. Swift production of
      interleukin (IL)-12 by tissue-resident XCR1+ conventional dendritic cells (cDC1)
      promoted ILC1 production of IFN-gamma in a STAT4-dependent manner to limit early
      viral burden. Thus, ILC1 contribute an essential role in viral immunosurveillance
      at sites of initial infection in response to local cDC1-derived proinflammatory
      cytokines.

PMID- 29056345
TI  - A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance.
AB  - Protein aggregation is a hallmark of many diseases but also underlies a wide
      range of positive cellular functions. This phenomenon has been difficult to study
      because of a lack of quantitative and high-throughput cellular tools. Here, we
      develop a synthetic genetic tool to sense and control protein aggregation. We
      apply the technology to yeast prions, developing sensors to track their
      aggregation states and employing prion fusions to encode synthetic memories in
      yeast cells. Utilizing high-throughput screens, we identify prion-curing mutants
      and engineer "anti-prion drives" that reverse the non-Mendelian inheritance
      pattern of prions and eliminate them from yeast populations. We extend our
      technology to yeast RNA-binding proteins (RBPs) by tracking their propensity to
      aggregate, searching for co-occurring aggregates, and uncovering a group of
      coalescing RBPs through screens enabled by our platform. Our work establishes a
      quantitative, high-throughput, and generalizable technology to study and control
      diverse protein aggregation processes in cells.

PMID- 29056344
TI  - Comprehensive Analysis of Hypermutation in Human Cancer.
AB  - We present an extensive assessment of mutation burden through sequencing analysis
      of >81,000 tumors from pediatric and adult patients, including tumors with
      hypermutation caused by chemotherapy, carcinogens, or germline alterations.
      Hypermutation was detected in tumor types not previously associated with high
      mutation burden. Replication repair deficiency was a major contributing factor.
      We uncovered new driver mutations in the replication-repair-associated DNA
      polymerases and a distinct impact of microsatellite instability and replication
      repair deficiency on the scale of mutation load. Unbiased clustering, based on
      mutational context, revealed clinically relevant subgroups regardless of the
      tumors' tissue of origin, highlighting similarities in evolutionary dynamics
      leading to hypermutation. Mutagens, such as UV light, were implicated in
      unexpected cancers, including sarcomas and lung tumors. The order of mutational
      signatures identified previous treatment and germline replication repair
      deficiency, which improved management of patients and families. These data will
      inform tumor classification, genetic testing, and clinical trial design.

PMID- 29056347
TI  - Addressing Professionalism, Social, and Communication Competencies in Surgical
      Residency Via Integrated Humanities Workshops: A Pilot Curriculum.
AB  - OBJECTIVE: We aimed to conduct professionalism and social competencies (PSC)
      training by integrating humanities into structured workshops, and to assess
      reception of this curriculum by first-year surgical residents. DESIGN: An IRB
      approved, pilot curriculum consisting of 4 interactive workshops for surgical
      interns was developed. The workshops were scheduled quarterly, often in small
      group format, and supplemental readings were assigned. Humanities media utilized
      to illustrate PSC included survival scenarios, reflective writing, television
      portrayals, and social media. Emphasis was placed on recognizing personal values
      and experiences that influence judgment and decision-making, using social media
      responsibly, identifying and overcoming communication barriers related to
      generational changes in training (especially technology and work-life balance),
      and tackling stereotypes of surgeons. Anonymous and voluntary pre- and
      postcurriculum surveys were administered. Univariate analysis of responses was
      performed with JMP Pro v12 using Fisher's exact, chi2, and Students' t-tests for
      categorical and continuous variables. SETTING: The study took place at the
      Cleveland Clinic in Cleveland, OH, within the general surgery program.
      PARTICIPANTS: Surgical interns at the Cleveland Clinic were included in the
      study. A total of 16 surgical interns completed the curriculum. RESULTS: Sixteen
      surgical interns participated in the curriculum: 69% were domestic medical school
      graduates (DG) and 31% were international medical school graduates (IMG).
      Overall, the majority (81%) of residents had received PSC courses during medical
      school: 100% of DG compared to 40% of IMG (p = 0.02). Before beginning the
      curriculum, 86% responded that additional PSC training would be useful during
      residency, which increased to 94% upon completion (p = 0.58). Mean number of
      responses supporting the usefulness of PSC training increased from 1.5 +/- 0.2
      before the curriculum to 1.75 +/- 0.2 upon completion (p = 0.4). When describing
      public and medical student perceptions of surgeons, 60% and 83% of adjectives
      used were negative, respectively. When describing perceptions of female surgeons,
      88% of adjectives used were negative. CONCLUSIONS: Most interns received prior
      PSC coursework; however, the majority still desired additional training during
      residency. After completion, a greater percentage of interns responded that PSC
      training was important and choose more reasons in favor of the curriculum.
      Formalized didactics should be strongly considered, especially in programs with
      IMG. Future areas of investigation include expanding the cohort to additional
      years of residency; potentially identifying unique PSC needs for each
      postgraduate year.

PMID- 29056346
TI  - Universal Patterns of Selection in Cancer and Somatic Tissues.
AB  - Cancer develops as a result of somatic mutation and clonal selection, but
      quantitative measures of selection in cancer evolution are lacking. We adapted
      methods from molecular evolution and applied them to 7,664 tumors across 29
      cancer types. Unlike species evolution, positive selection outweighs negative
      selection during cancer development. On average, <1 coding base
      substitution/tumor is lost through negative selection, with purifying selection
      almost absent outside homozygous loss of essential genes. This allows exome-wide
      enumeration of all driver coding mutations, including outside known cancer genes.
      On average, tumors carry ~4 coding substitutions under positive selection,
      ranging from <1/tumor in thyroid and testicular cancers to >10/tumor in
      endometrial and colorectal cancers. Half of driver substitutions occur in yet-to
      be-discovered cancer genes. With increasing mutation burden, numbers of driver
      mutations increase, but not linearly. We systematically catalog cancer genes and
      show that genes vary extensively in what proportion of mutations are drivers
      versus passengers.

PMID- 29056348
TI  - International patellofemoral osteoarthritis consortium: Consensus statement on
      the diagnosis, burden, outcome measures, prognosis, risk factors and treatment.
AB  - OBJECTIVE: To present the current status of knowledge in the field of
      patellofemoral (PF) osteoarthritis (OA) and formulate a research agenda in order
      to guide future research on this topic. DESIGN: A 1-day meeting was organized
      with the aim to bring together international experts in the field to discuss the
      current state of knowledge on PF OA. Experts from multiple disciplines were
      invited based on their scientific publications in the field of PF OA and interest
      in the subject. Topics discussed include the diagnosis, impact, prognosis, and
      treatment of PF OA. METHODS: Following context-setting presentations, an
      interactive discussion was held in order to achieve consensus on the PF OA topics
      of interest: (1) diagnosis and definition; (2) burden; (3) outcome measures; (4)
      prognosis; (5) risk factors, and (6) treatment. Groups of meeting attendees
      reviewed the literature on these topics and narratively summarized the current
      state of knowledge, and each group formulated research agenda items relevant to
      the specific topics of interest. Each consortium member consequently ranked the
      importance of all items on a 0-10 Numerical Rating Scale (NRS) (10 = extremely
      important, to 0 = not at all important). RESULTS: After ranking all formulated
      items on importance, 6 of the 28 research agenda items formulated received an
      average of 7.5 points on the NRS. The most highly ranked items covered the fields
      of treatment, diagnosis, and definition of PF OA. CONCLUSIONS: We recommend to
      develop clear clinical criteria for PF OA and to reach consensus on the
      definition of PF OA by both radiographs and MRI. Additionally, more understanding
      is necessary to be able to distinguish PF symptoms from those arising from the
      tibiofemoral joint. More insight is needed on effective treatment strategies for
      PF OA; specifically, tailoring nonpharmacological treatments to individuals with
      PF OA, and determining whether isolated PF OA requires different treatment
      strategies than combined PF and tibiofemoral OA.

PMID- 29056349
TI  - Clinical characteristics of spontaneous isolated visceral artery dissection.
AB  - OBJECTIVE: Spontaneous isolated visceral artery dissection (SIVAD) involving the
      celiac artery or superior mesenteric artery is rare, but it can be fatal. Given
      its rare incidence, the clinical characteristics of SIVAD are not fully
      understood. Therefore, the aim of this study was to investigate the clinical
      characteristics and prognosis of SIVAD. METHODS: We retrospectively reviewed 39
      consecutive patients diagnosed with SIVAD from January 2007 to December 2016.
      Demographic characteristics, symptoms, vital signs, blood examination results,
      and computed tomography findings were retrieved through medical record review.
      RESULTS: The median age of the patients was 52 years; 94.9% were male, and 64.1%
      were symptomatic. Median follow-up duration was 11 months. Overall, hypertension
      (48.7%) and smoking (79.5%) were frequently observed. There were significant
      differences between symptomatic and asymptomatic patients in white blood cell
      count and creatine kinase level but not in fibrin degradation products or D-dimer
      level. There was a significant correlation between symptoms and length of
      dissection on computed tomography (P < .01). Conservative treatment was performed
      in 32 patients (82.1%), and only 7 patients required open surgery or
      intravascular intervention. Notably, the diameter of affected vessels decreased
      spontaneously with no rupture or symptom recurrence during follow-up, and
      mortality was 0% at both 30 days and 1 year. CONCLUSIONS: The utility of blood
      examination, especially for fibrin degradation products and D-dimer levels, for
      diagnosis of SIVAD is limited. A high index of suspicion is warranted in patients
      presenting with persistent severe abdominal pain. Conservative treatment should
      be considered first-line therapy in patients without any signs of bowel ischemia
      or rupture.

PMID- 29056350
TI  - Late patency of reconstructed visceral arteries after open repair of
      thoracoabdominal aortic aneurysm.
AB  - BACKGROUND: In the era of rising endovascular treatment of thoracoabdominal
      aortic aneurysms (TAAAs), the analysis of visceral vessel (VV) patency after open
      surgical repair is crucial to provide a future benchmark between these different
      approaches. This study reports the late outcomes of a single-center experience
      with open TAAA repair, focusing on the results of different techniques adopted
      for renal and splanchnic revascularization. METHODS: Data were analyzed for 382
      consecutive open TAAA repairs performed between January 2009 and July 2015 (284
      men; mean age, 66 +/- 10 years). Follow-up of surviving patients was carried out
      by computed tomography angiography and office checkups at 3 and 12 months and
      yearly afterward. Kaplan-Meier analysis was performed for overall survival,
      patency of reconstructed VVs (celiac trunk, superior mesenteric artery, right
      renal artery, left renal artery), and reinterventions on visceral arteries.
      Furthermore, VV long-term patency was analyzed in subgroups of patients according
      to the revascularization strategy (patch inclusion of all vessels, group 1; one
      vessel separate reattachment and patch inclusion of the remaining vessels, group
      2; separate reattachment of all VVs, group 3). RESULTS: In-hospital mortality and
      paraparesis/paraplegia occurred in 7.6% and 8.1% of patients, respectively. Among
      the 353 survivors, 338 complied with the follow-up protocol, and adequate
      computed tomography angiography images were available in 247 patients (952 VVs
      were analyzed). Overall follow-up survival was 94%, 91%, and 70% at 1 year, 2
      years, and 5 years, respectively. At the same time points, VV patency was 99%,
      98%, and 98% for celiac trunk; 100%, 100%, and 100% for superior mesenteric
      artery; 100%, 96%, and 96% for right renal artery; and 91%, 87%, and 82% for left
      renal artery (log-rank test, P < .0001). Estimates for reinterventions on VVs
      were 1.2%, 6.3%, and 17% at the same time points. Freedom from occlusion of any
      VV at 1 year and 3 years was 95% and 87% for group 1, 89% and 79% for group 2,
      and 92% and 92% for group 3, respectively (log-rank test, P = .13). CONCLUSIONS:
      Long-term patency of VVs after open TAAA repair performed in high-volume centers
      is high, regardless of the technique employed for revascularization. The left
      renal artery appears to be most prone to occlusion over time.

PMID- 29056351
TI  - Estradiol increases choice of cocaine over food in male rats.
AB  - Estradiol modulates the rewarding and reinforcing properties of cocaine in
      females, including an increase in selection of cocaine over alternative
      reinforcers. However, the effects of estradiol on male cocaine self
      administration behavior are less studied despite equivalent levels of estradiol
      in the brains of adult males and females, estradiol effects on motivated
      behaviors in males that share underlying neural substrates with cocaine
      reinforcement as well as expression of estrogen receptors in the male brain.
      Therefore, we sought to characterize the effects of estradiol in males on choice
      between concurrently-available cocaine and food reinforcement as well as
      responding for cocaine or food in isolation. Male castrated rats (n=46) were
      treated daily with estradiol benzoate (EB) (5MUg/0.1, S.C.) or vehicle (peanut
      oil) throughout operant acquisition of cocaine (1mg/kg, IV; FI20 sec) and food
      (3*45mg; FI20 sec) responding, choice during concurrent access and cocaine and
      food reinforcement under progressive ratio (PR) schedules. EB increased cocaine
      choice, both in terms of percent of trials on which cocaine was selected and the
      proportion of rats exhibiting a cocaine preference as well as increased cocaine,
      but not food, intake under PR. Additionally, within the EB treated group, cocaine
      preferring rats exhibited enhanced acquisition of cocaine, but not food,
      reinforcement whereas no acquisition differences were observed across preferences
      in the vehicle treated group. These findings demonstrate that estradiol increases
      cocaine choice in males similarly to what is observed in females.

PMID- 29056352
TI  - Does MCH play a role on establishment or maintenance of social hierarchy in Nile
      tilapia?
AB  - Body coloration has a fundamental role in animal communication by signaling sex,
      age, reproductive behavior, aggression, etc. Nile-tilapia exhibits dominance
      hierarchy and the dominants are paler than subordinates. During social
      interactions in these animals, these color changes occur rapidly, and normally
      the subordinates become dark. In teleosteans, from the great number of hormones
      and neurotransmitters involved in color changes, melanocyte hormone stimulates
      (alpha-MSH) and melanin concentrates hormone (MCH) are the most remarkable. The
      aim of this project was to investigate the role of MCH in the establishment of
      hierarchical dominance of the Nile-tilapia. We analyzed the effect of background
      coloration in the dominance hierarchy. It was then compared to the melanophore
      sensibility of dominants and subordinates' fishes to MCH; finally, it was checked
      if the social rank affects the number of these pigment cells in dominants and
      subordinated fishes. Fishes which have a social hierarchy established and
      adjusted individually to the background exhibits paler body coloration when a
      visual contact was possible, independently of previous social rank and background
      color. Probably, even recognizing each other, fishes could be defending their new
      territory. Melanophores of the subordinate fishes were more sensible to MCH than
      dominants. It suggests that dominants fishes, which are paler than subordinates,
      could be under a chronic effect of MCH, which could be due a desensitization of
      melanophores to this hormone. The opposite effect seems to be occurring on
      subordinate fishes. It was not observed a significant change in the number of
      melanophores when the fishes were exposed to a prolonged period of agonistic
      interaction. It is possible that the exposure time for this interaction might not
      have been sufficient to have any change in the number of these cells of dominants
      and subordinate fishes.

PMID- 29056353
TI  - The GHR-R antagonist JMV 2959 neither induces malaise nor alters the malaise
      property of LiCl in the adult male rat.
AB  - The orexigenic peptide ghrelin (GHR) interacts with ghrelin receptors (GHR-Rs) to
      modulate brain reinforcement and feeding circuits. Pharmacological inactivation
      of GHR-Rs via administration of the drug JMV 2959 attenuates the
      rewarding/reinforcing effects of several drugs of abuse including alcohol,
      morphine, amphetamine and nicotine. One view of these results is that
      inactivation of GHR-Rs taps into brain reinforcement/feeding circuits acted upon
      by drugs of abuse. An alternate explanation is that JMV 2959 may induce malaise,
      which in turn may limit reinforcement as well as food ingestion. This is a
      variable of interest given that nicotine alone can induce malaise which may be
      enhanced by JMV 2959. In the present study, we assessed the capacity of JMV 2959
      to produce malaise using a conditioned taste aversion (CTA) task. Adult male rats
      were allowed to consume a 0.1% sodium saccharin solution and then injected IP
      with either vehicle, 0.4mg/kg nicotine, 3mg/kg JMV 2959, a combination of
      0.4mg/kg nicotine and 3mg/kg JMV 2959, or 32mg/kg lithium chloride (a positive
      control known to support induction of CTA). Lithium chloride produced a robust
      avoidance of the saccharin solution in subsequent 2 bottle (water and saccharin)
      tests, whereas JMV 2959 alone did not induce CTA. The combination of JMV 2959 and
      nicotine induced a moderate degree of CTA that was similar to that produced by
      nicotine alone. These results suggest that JMV 2959 is unlikely to limit either
      reinforcement or food ingestion via induction of malaise.

PMID- 29056354
TI  - Resorption of the mandibular condyle after injections of botulinum toxin A.

PMID- 29056355
TI  - Three-dimensional macroporous materials for tissue engineering of craniofacial
      bone.
AB  - Repair of critical-size defects caused by trauma, removal of a tumour, or
      congenital abnormalities is a challenge in the craniomaxillofacial region because
      of the limitations associated with treatment. We have reviewed research papers
      and updated information relevant to the various types of macroporous scaffolds.
      We have included papers on several biomaterials and their use in various
      craniofacial defects such as mandibular, calvarial, and others, as well as the
      latest technological developments such as 3-dimensional printed scaffolds. We
      selected all papers about scaffolds, stem cells, and growth factors for review.
      Initial selection was by review of titles and abstracts, and the full texts of
      potentially suitable articles were then assessed. Methods of tissue engineering
      for repair of critical-size defects in the craniofacial bones seem to be viable
      options for surgical treatment in the future. Macroporous scaffolds with
      interconnected pores are of great value in regeneration of bone in the
      craniofacial region. In recent years, various natural or synthetic materials, or
      both, have been developed, on which macroporous scaffolds can be based. In this
      review we present a review on the various types of three-dimensional macroporous
      scaffolds that have been developed in recent years, and evaluate their potential
      for regeneration of craniofacial bone.

PMID- 29056356
TI  - Perioperative primary herpetic stomatitis of an intraoral skin paddle that
      mimicked compromise of the free flap.

PMID- 29056357
TI  - Modified T-shaped incision for the treatment of bilateral conditions of the oral
      floor.

PMID- 29056358
TI  - Calcification of a huge orthokeratinised odontogenic cyst: a rare case of
      plugging with polymethylmethacrylate after curettage.

PMID- 29056359
TI  - Sortilin inhibits amyloid pathology by regulating non-specific degradation of
      APP.
AB  - Amyloid plaque is one of the hallmarks of Alzheimer's disease (AD). The key
      component beta-amyloid (Abeta) is generated via proteolytic processing of amyloid
      precursor protein (APP). Sortilin (encoded by the gene Sort1) is a vacuolar
      protein sorting 10 protein domain-containing receptor, which is up-regulated in
      the brain of AD, colocalizes with amyloid plaques and interacts with APP.
      However, its role in amyloidogenesis remains unclear. In this study, we first
      found that the protein level of sortilin was up-regulated in the neocortex of
      aged (7 and 9months old) but not young (2 and 5months old) AD mice (APP/PS1).
      9months old APP/PS1 transgenic mice with Sort1 gene knockout showed increased
      amyloid pathology in the brain; and this phenotype was rescued by
      intrahippocampal injection of AAV-hSORT1. Moreover, the 9months old APP/PS1 mice
      without Sort1 also displayed a decreased number of neurons and increased
      astrocyte activation in the hippocampus. In addition, the present study showed
      that the intracellular domain of sortilin was involved in the regulation of the
      non-specific degradation of APP. Together, our findings indicate that sortilin is
      a beneficial protein for the reduction of amyloid pathology in APP/PS1 mice by
      promoting APP degradation.

PMID- 29056360
TI  - Photobiomodulation therapy promotes neurogenesis by improving post-stroke local
      microenvironment and stimulating neuroprogenitor cells.
AB  - Recent work has indicated that photobiomodulation (PBM) may beneficially alter
      the pathological status of several neurological disorders, although the mechanism
      currently remains unclear. The current study was designed to investigate the
      beneficial effect of PBM on behavioral deficits and neurogenesis in a
      photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after
      the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm2, total
      294J at scalp level) was applied on the infarct injury area (1.8mm anterior to
      the bregma and 2.5mm lateral from the midline). Rats received intraperitoneal
      injections of 5-bromodeoxyuridine (BrdU) twice daily (50mg/kg) from day 2 to 8
      post-stoke, and samples were collected at day 14. We demonstrated that PBM
      significantly attenuated behavioral deficits and infarct volume induced by PT
      stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis
      and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2,
      spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects
      of PBM were accompanied by robust suppression of reactive gliosis and the
      production of pro-inflammatory cytokines. On the contrary, the release of anti
      inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri
      infarct regions were elevated following PBM treatment. Intriguingly, PBM could
      effectively switch an M1 microglial phenotype to an anti-inflammatory M2
      phenotype. Our novel findings indicated that PBM is capable of promoting
      neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1)
      promotion of proliferation and differentiation of internal neuroprogenitor cells
      in the peri-infarct zone; 2) improvement of the neuronal microenvironment by
      altering inflammatory status and promoting mitochondrial function. These findings
      provide strong support for the promising therapeutic effect of PBM on neuronal
      repair following ischemic stroke.

PMID- 29056361
TI  - Compensatory plasticity in diaphragm and intercostal muscle utilization in a rat
      model of ALS.
AB  - In SOD1G93A transgenic rat model of ALS, breathing capacity is preserved until
      late in disease progression despite profound respiratory motor neuron (MN) cell
      death. To explore mechanisms preserving breathing capacity, we assessed
      inspiratory EMG activity in diaphragm and external intercostal T2 (EIC2) and T5
      (EIC5) muscles in anesthetized SOD1G93A rats at disease end-stage (20% decrease
      in body mass). We hypothesized that despite significant phrenic motor neuron loss
      and decreased phrenic nerve activity, diaphragm electrical activity and trans
      diaphragmatic pressure (Pdi) are maintained to sustain ventilation. We
      alternatively hypothesized that EIC activity is enhanced, compensating for
      impaired diaphragm function. Diaphragm, EIC2 and EIC5 muscle EMGs and Pdi were
      measured in urethane-anesthetized, spontaneously breathing female SOD1G93A rats
      versus wild-type littermates during normoxia (arterial PO2 ~90mmHg, PCO2
      ~45mmHg), maximal chemoreceptor stimulation (MCS: 10.5% O2/7% CO2), spontaneous
      augmented breaths and sustained tracheal occlusion. Phrenic MNs were counted in
      C3-5; T2 and T5 ventrolateral MNs were counted. In end-stage SOD1G93A rats, 29%
      of phrenic MNs survived (vs. wild-type), yet integrated diaphragm EMG amplitude
      was normal. Nevertheless, maximal Pdi decreased ~30% vs. wild type (p<0.01) and
      increased esophageal to gastric pressure ratio (p<0.05), consistent with
      persistent diaphragm weakness. Despite major T2 and T5 MN death, integrated EIC2
      (100% greater than wild type) and EIC5 (300%) EMG amplitudes were increased in
      mutant rats during normoxia (p<0.01), possibly compensating for decreased Pdi.
      Thus, despite significant phrenic MN loss, diaphragm EMG activity is maintained;
      in contrast, Pdi was not, suggesting diaphragm dysfunction. Presumably, increased
      EIC EMG activity compensated for persistent diaphragm weakness. These adjustments
      contribute to remarkable preservation of breathing ability despite major
      respiratory motor neuron death and diaphragm dysfunction.

PMID- 29056363
TI  - Pramipexole reduces soluble mutant huntingtin and protects striatal neurons
      through dopamine D3 receptors in a genetic model of Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by abnormal
      expansion of the polyglutamine tract in the huntingtin protein (HTT). The
      toxicity of mutant HTT (mHTT) is associated with intermediate mHTT soluble
      oligomers that subsequently form intranuclear inclusions. Thus, interventions
      promoting the clearance of soluble mHTT are regarded as neuroprotective. Striatal
      neurons are particularly vulnerable in HD. Their degeneration underlies motor
      symptoms and striatal atrophy, the anatomical hallmark of HD. Recent studies
      indicate that autophagy may be activated by dopamine D2 and D3 receptor (D2R/D3R)
      agonists. Since autophagy plays a central role in the degradation of misfolded
      proteins, and striatal neurons express D2R and D3R, D2R/D3R agonists may promote
      the clearance of mHTT in striatal neurons. Here, this hypothesis was tested by
      treating 8-week old R6/1 mice with the D2R/D3R agonist pramipexole for 4weeks.
      Pramipexole reduced striatal levels of soluble mHTT and increased the size of
      intranuclear inclusions in R6/1 mice. Furthermore, striatal DARPP-32 levels and
      motor functions were recovered. These effects were accompanied by an increase in
      LC3-II and a decrease in p62 in the striatum. Tollip, a selective adaptor of
      ubiquitinated polyQ proteins to LC3, was also reduced in the striata of R6/1mice
      but not in their wild-type littermates. No changes were detected in the cerebral
      cortex where D3R expression is very low, and behavioral and biochemical effects
      in the striatum were prevented by a D3R antagonist. The findings indicate that
      PPX protects striatal neurons by promoting the clearance of soluble mHTT through
      a D3R-mediated mechanism. The evidence of autophagy markers suggests that
      autophagy is activated, although it is not efficient at removing all mHTT
      recruited by the autophagic machinery as indicated by the increase in the size of
      intranuclear inclusions.

PMID- 29056365
TI  - Computational human head models of tDCS: Influence of brain atrophy on current
      density distribution.
AB  - : Despite increasing attention to the application of transcranial Direct Current
      Stimulation (tDCS) for enhancing cognitive functions in subjects exposing to
      varying degree of cerebral atrophy such as Alzheimer's disease (AD), aging, and
      mild cognitive impairment (MCI), there is no general information for customizing
      stimulation protocol. OBJECTIVE: The objective of this study is to examine how
      cerebral shrinkage associated with cognitive impairment and aging can perturb
      current density distribution through the brain. METHODS: We constructed three
      high-resolution human head models representing young, elder, and MCI subjects and
      modeled two electrode configurations using rectangular electrodes. RESULTS: Our
      results showed that decreasing gray matter volume in MCI, as well as aging,
      reduced the magnitude of the current density in the brain compared to the young
      model. Also, morphology alterations of the cerebral sulcus could shape the
      vectors of the current density to flow in the depth of cortical regions by
      cerebrospinal fluid. CONCLUSION: This study provides a framework for further
      advanced studies in establishing new methodologies or modifying stimulation
      parameters.

PMID- 29056364
TI  - Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic
      spinal cord injury.
AB  - Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role
      in lipid and cholesterol metabolism, has also been implicated in many
      neurological diseases. In this study, we examined the effect of apoE on the
      pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant
      (apoE-/-) and wild-type mice received a T9 moderate contusion SCI and were
      evaluated using histological and behavioral analyses after injury. At 3days after
      injury, the permeability of spinal cord-blood-barrier, measured by extravasation
      of Evans blue dye, was significantly increased in apoE-/- mice compared to wild
      type. The inflammation and spared white matter was also significantly increased
      and decreased, respectively, in apoE-/- mice compared to the wild type ones. The
      apoptosis of both neurons and oligodendrocytes was also significantly increased
      in apoE-/- mice. At 42days after injury, the inflammation was still robust in the
      injured spinal cord in apoE-/- but not wild type mice. CD45+ leukocytes from
      peripheral blood persisted in the injured spinal cord of apoE-/- mice. The spared
      white matter was significantly decreased in apoE-/- mice compared to wild type
      ones. Locomotor function was significantly decreased in apoE-/- mice compared to
      wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE
      mimetic peptides partially restored the permeability of spinal cord-blood-barrier
      in apoE-/- mice after SCI. Importantly, the exogenous apoE peptides decreased
      inflammation, increased spared white matter and promoted locomotor recovery in
      apoE-/- mice after SCI. Our results indicate that endogenous apoE plays important
      roles in maintaining the spinal cord-blood-barrier and decreasing inflammation
      and spinal cord tissue loss after SCI, suggesting its important neuroprotective
      function after SCI. Our results further suggest that exogenous apoE mimetic
      peptides could be a novel and promising neuroprotective reagent for SCI.

PMID- 29056362
TI  - Critical appraisal of pathology transmission in the alpha-synuclein fibril model
      of Lewy body disorders.
AB  - Lewy body disorders are characterized by the emergence of alpha-synucleinopathy
      in many parts of the central and peripheral nervous systems, including in the
      telencephalon. Dense alpha-synuclein+ pathology appears in regio inferior of the
      hippocampus in both Parkinson's disease and dementia with Lewy bodies and may
      disturb cognitive function. The preformed alpha-synuclein fibril model of
      Parkinson's disease is growing in use, given its potential for seeding the self
      propagating spread of alpha-synucleinopathy throughout the mammalian brain.
      Although it is often assumed that the spread occurs through neuroanatomical
      connections, this is generally not examined vis-a-vis the uptake and transport of
      tract-tracers infused at precisely the same stereotaxic coordinates. As the
      neuronal connections of the hippocampus are historically well defined, we
      examined the first-order spread of alpha-synucleinopathy three months following
      fibril infusions centered in the mouse regio inferior (CA2+CA3), and contrasted
      this to retrograde and anterograde transport of the established tract-tracers
      FluoroGold and biotinylated dextran amines (BDA). Massive hippocampal alpha
      synucleinopathy was insufficient to elicit memory deficits or loss of cells and
      synaptic markers in this model of early disease processes. However, dense alpha
      synuclein+ inclusions in the fascia dentata were negatively correlated with
      memory capacity. A modest compensatory increase in synaptophysin was evident in
      the stratum radiatum of cornu Ammonis in fibril-infused animals, and
      synaptophysin expression correlated inversely with memory function in fibril but
      not PBS-infused mice. No changes in synapsin I/II expression were observed. The
      spread of alpha-synucleinopathy was somewhat, but not entirely consistent with
      FluoroGold and BDA axonal transport, suggesting that variables other than
      innervation density also contribute to the materialization of alpha
      synucleinopathy. For example, layer II entorhinal neurons of the perforant
      pathway exhibited somal alpha-synuclein+ inclusions as well as retrogradely
      labeled FluoroGold+ somata. However, some afferent brain regions displayed dense
      retrograde FluoroGold label and no alpha-synuclein+ inclusions (e.g. medial
      septum/diagonal band), supporting the selective vulnerability hypothesis. The
      pattern of inclusions on the contralateral side was consistent with specific
      spread through commissural connections (e.g. stratum pyramidale of CA3), but
      again, not all commissural projections exhibited alpha-synucleinopathy (e.g.
      hilar mossy cells). The topographical extent of inclusions is displayed here in
      high-resolution images that afford viewers a rich opportunity to dissect the
      potential spread of pathology through neural circuitry. Finally, the results of
      this expository study were leveraged to highlight the challenges and limitations
      of working with preformed alpha-synuclein fibrils.

PMID- 29056367
TI  - Burns caused by electronic vaping devices (e-cigarettes): A new classification
      proposal based on mechanisms.
AB  - Introduction With more than 10 million of daily users, e-cigarettes encountered a
      great success. But in the past few years, the number of medical reports of
      injuries caused by the explosion of e-cigarettes has significantly increased.
      This article aims at reporting our series and reviewing the literature to propose
      a new classification based on the mechanisms of injuries related to e-cigarettes
      that can guide non-specialists and specialists in the management of these
      patients. Method We performed a retrospective review of our institutional burn
      database from June 2016 to July 2017 for injuries caused by or in the context of
      using an e-cigarette. The patients' demographics (age, gender), burn injury
      mechanisms, depth, localization, surface and interventions were described.
      Results Ten patients suffered from burns related to the use of e-cigarettes. The
      burns were located at the thigh (80%) and the hand (50%) with a mean surface of
      3% of TBSA. Four different mechanisms could be described: Type A: thermal burns
      with flames due to the phenomenon of "thermal runaway", Type B: blasts lesions
      secondary to the explosion, Type C: chemical alkali burns caused by spreading of
      the electrolyte solution and Type D: thermal burns without flames due to
      overheating. These different mechanisms suggest specific surgical and non
      surgical management. Conclusion Management of injuries sustained from e
      cigarettes' explosions should be approached from the standpoint of mechanisms.
      Different mechanisms could be associated and should be considered in specific
      management.

PMID- 29056366
TI  - Natural modulators of nonalcoholic fatty liver disease: Mode of action analysis
      and in silico ADME-Tox prediction.
AB  - Nonalcoholic fatty liver disease (NAFLD) is considered to be the most common
      chronic liver disease. The discovery of natural product-based NAFLD modulators
      requires a more comprehensive study of their modes of action (MoAs). In this
      study we analysed available in the literature data for 26 naturally-derived
      compounds associated with experimental evidence for NAFLD alleviation and
      outlined potential biomolecular targets and a network of pharmacological MoAs for
      12 compounds with the highest number of experimentally supported MoA key events,
      modulated by them. Despite the general perception that the therapeutic agents of
      natural origin are safe, an evaluation of ADME-Tox properties of these compounds
      has also been performed in order to estimate their suitability as drug
      candidates. We evaluated how the investigated structures fit to Lipinski's "Rule
      of five" and predicted their potential Phase I biotransformation pathways and
      toxicological effects using the ACD/Percepta platform, and the Meteor Nexus and
      Derek Nexus knowledge-based systems. Our results revealed the potential of the
      studied compounds as lead structures and outlined those of them that needed
      further optimisation of their pharmacokinetic profiles. The presented combined
      MoA/in silico approach could be extrapolated to naturally-derived and pathology
      relevant lead structures with other biological activities. It could direct their
      optimisation by a mechanistically justified in silico evaluation.

PMID- 29056368
TI  - Transcranial direct current stimulation of dorsolateral prefrontal cortex during
      encoding improves recall but not recognition memory.
AB  - Prior work demonstrates that application of transcranial direct current
      stimulation (tDCS) improves memory. In this study, we investigated tDCS effects
      on face-name associative memory using both recall and recognition tests.
      Participants encoded face-name pairs under either active (1.5mA) or sham (.1mA)
      stimulation applied to the scalp adjacent to the left dorsolateral prefrontal
      cortex (dlPFC), an area known to support associative memory. Participants' memory
      was then tested after study (day one) and then again after a 24-h delay (day
      two), to assess both immediate and delayed stimulation effects on memory. Results
      indicated that active relative to sham stimulation led to substantially improved
      recall (more than 50%) at both day one and day two. Recognition memory
      performance did not differ between stimulation groups at either time point. These
      results suggest that stimulation at encoding improves memory performance by
      enhancing memory for details that enable a rich recollective experience, but that
      these improvements are evident only under some testing conditions, especially
      those that rely on recollection. Overall, stimulation of the dlPFC could have led
      to recall improvement through enhanced encoding from stimulation or from
      carryover effects of stimulation that influenced retrieval processes, or both.

PMID- 29056369
TI  - Cryoconites from Alpine glaciers: Radionuclide accumulation and age estimation
      with Pu and Cs isotopes and 210Pb.
AB  - Cryoconites ("cold dust", derived from the Greek) are aeolian sediments
      accumulated on glacier surfaces. In cryoconites from the surface of the Stubacher
      Sonnblickkees, a temperate Austrian glacier, extremely high activity
      concentrations of artificial and natural radionuclides were found. Artificial
      radionuclides stem from two clearly distinguishable sources, global fallout from
      the nuclear weapons testing era deposited over a period of years until roughly
      1966 and the fallout from Chernobyl in 1986, which was essentially deposited as a
      single input during one week. Anthropogenic radionuclides identified were 137Cs,
      134Cs, 238Pu, 239+240Pu, 90Sr, 241Am, 60Co, 125Sb, 154Eu, and 207Bi. The
      naturally occurring radionuclides detected were the long-lived radon decay
      product 210Pb, the primordial radionuclide 4 K and the cosmogenic 7Be. Isotopic
      ratios of 134Cs/137Cs and 239+240Pu/238Pu were used to separate the nuclide
      inventory into the contributions of the two aforementioned sources, which show
      varying degrees of mixing and provide information on the mixing age of the
      cryoconites. Since isotopic ratios of Pu often have high uncertainties due to low
      absolute concentrations, age estimation based on this method can be quite
      inaccurate. Additional information about the age of cryoconites was obtained
      through analysis of 210Pb, which is constantly deposited over time.

PMID- 29056370
TI  - Trends in Sodium Content of Menu Items in Large Chain Restaurants in the U.S.
AB  - INTRODUCTION: Consuming too much sodium is associated with increased risk for
      cardiovascular disease, and restaurant foods are a primary source of sodium. This
      study assessed recent trends in sodium content of menu items in U.S. chain
      restaurants. METHODS: Data from 21,557 menu items in 66 top-earning chain
      restaurants available from 2012 to 2016 were obtained from the MenuStat project
      and analyzed in 2017. Generalized linear models were used to examine changes in
      calorie-adjusted, per-item sodium content of menu items offered in all years
      (2012-2016) and items offered in 2012 only compared with items newly introduced
      in 2013, 2014, 2015, and 2016. RESULTS: Overall, calorie-adjusted sodium content
      in newly introduced menu items declined by 104 mg from 2012 to 2016 (p<0.02).
      However, the magnitude and direction of these changes varied by menu category and
      restaurant type; sodium content, particularly for main course items, was high.
      Sodium declined by 83 mg in fast food restaurants, 19 mg in fast casual
      restaurants, and 163 mg in full service restaurants. Sodium in appetizer and side
      items newly introduced in 2016 increased by 266 mg compared with items on the
      menu in 2012 only (p<0.01). Sodium in main courses newly introduced in 2016
      declined by 124 mg compared with items on the menu in 2012 only (p=0.01), with
      the greatest decline, 207 mg (p=0.03), among salads. CONCLUSIONS: Average,
      adjusted, per-item sodium content was lower in newly introduced items in large
      chain restaurants. However, sodium content of core and new menu items remain
      high, and reductions are inconsistent across menu categories and restaurant
      types.

PMID- 29056371
TI  - Preventive Service Use Among People With and Without Serious Mental Illnesses.
AB  - INTRODUCTION: People with serious mental illnesses experience excess morbidity
      and premature mortality resulting from preventable conditions. The goal was to
      examine disparities in preventive care that might account for poor health
      outcomes. METHODS: In this retrospective cohort study, adults (N=803,276) served
      by Kaiser Permanente Northwest and federally qualified health centers/safety-net
      community health clinics were categorized into five groups: schizophrenia
      spectrum disorders, bipolar disorders/affective psychoses, anxiety disorders,
      nonpsychotic unipolar depression, and reference groups with no evidence of these
      specific mental illnesses. The primary outcome was overall preventive care-gap
      rate, the proportion of incomplete preventive services for which each patient was
      eligible in 2012-2013. Secondary analyses examined Kaiser Permanente Northwest
      data from 2002 to 2013. Data were analyzed in 2015. RESULTS: Controlling for
      patient characteristics and health services use, Kaiser Permanente Northwest mean
      care-gap rates were significantly lower for bipolar disorders/affective psychoses
      (mean=18.6, p<0.001) and depression groups (mean=18.6, p<0.001) compared with the
      reference group. Schizophrenia (mean=19.4, p=0.236) and anxiety groups
      (mean=19.9, p=0.060) did not differ from the reference group (mean=20.3). In
      community health clinics, schizophrenia (mean=34.1, p<0.001), bipolar/affective
      psychosis (mean=35.7, p<0.001), anxiety (mean=38.5, p<0.001), and depression
      groups (mean=36.3, p<0.001) had significantly lower care-gap rates than those in
      the reference group (mean=40.0). Secondary analyses of diabetes and dyslipidemia
      screening trends in Kaiser Permanente Northwest showed diagnostic groups
      consistently had fewer care gaps than patients in the reference group.
      CONCLUSIONS: In vastly different settings, individuals with serious mental
      illnesses received preventive services at equal or better rates than the general
      population.

PMID- 29056372
TI  - Walking in Relation to Mortality in a Large Prospective Cohort of Older U.S.
      Adults.
AB  - INTRODUCTION: Engaging in >150 minutes of moderate-intensity or 75 minutes of
      vigorous-intensity physical activity weekly is recommended for optimal health.
      The relationship between walking, the most common activity especially for older
      adults, and total mortality is not well documented. METHODS: Data from a large
      U.S. prospective cohort study including 62,178 men (mean age 70.7 years) and
      77,077 women (mean age 68.9 years), among whom 24,688 men and 18,933 women died
      during 13 years of follow-up (1999-2012), were used to compute multivariable
      adjusted hazard rate ratios and 95% CIs for walking as the sole form of activity
      or adjusted for other moderate- or vigorous-intensity physical activity in
      relation to total and cause-specific mortality (data analysis 2015-2016).
      RESULTS: Inactivity compared with walking only at less than recommended levels
      was associated with higher all-cause mortality (hazard rate ratio=1.26, 95%
      CI=1.21, 1.31). Meeting one to two times the recommendations through walking only
      was associated with lower all-cause mortality (hazard rate ratio=0.80, 95%
      CI=0.78, 0.83). Associations with walking adjusted for other moderate- or
      vigorous-intensity physical activity were similar to walking only. Walking was
      most strongly associated with respiratory disease mortality followed by
      cardiovascular disease mortality and then cancer mortality. CONCLUSIONS: In older
      adults, walking below minimum recommended levels is associated with lower all
      cause mortality compared with inactivity. Walking at or above physical activity
      recommendations is associated with even greater decreased risk. Walking is
      simple, free, and does not require any training, and thus is an ideal activity
      for most Americans, especially as they age.

PMID- 29056373
TI  - JTE-852, a novel spleen tyrosine kinase inhibitor, blocks immunoglobulin G
      mediated cellular responses and autoimmune reactions in vivo.
AB  - AIMS: Immune and inflammatory responses mediated by immunoglobulin (Ig) G are
      largely responsible for the pathogenesis of autoimmune diseases. Spleen tyrosine
      kinase (Syk) plays a pivotal role in the IgG-mediated responses; therefore, Syk
      has emerged as a new therapeutic target for the treatment of autoimmune diseases.
      In this study, we investigated the inhibitory actions of JTE-852, a novel Syk
      inhibitor, on IgG-mediated cellular responses and autoimmune reactions in vivo.
      MAIN METHODS: We examined mediator secretion from human monocytes. We also
      conducted rat models of reversed cutaneous anaphylaxis (RCA) and reversed passive
      Arthus (RPA), which are classified as type II and type III hypersensitivities,
      respectively. In a rat collagen-induced arthritis (CIA) model, JTE-852 or
      methotrexate was administered preventively (before the onset of arthritis) or
      therapeutically (after the onset of arthritis). KEY FINDINGS: JTE-852 blocked
      secretion of reactive oxygen species and tumor necrosis factor-alpha from
      monocytes stimulated by IgG crosslinking. In the RCA and RPA models, JTE-852 also
      suppressed edema and dye leakage, respectively. In the CIA model, JTE-852 showed
      both preventive and therapeutic effects against joint swelling and bone erosion;
      on the other hand, methotrexate did not show the therapeutic effect.
      SIGNIFICANCE: JTE-852 attenuates IgG-mediated responses and signs in animal model
      of autoimmune diseases. JTE-852 is thus a promising candidate for a novel, orally
      available drug for the treatment of autoimmune diseases.

PMID- 29056374
TI  - Describing the role of Drosophila melanogaster ABC transporters in insecticide
      biology using CRISPR-Cas9 knockouts.
AB  - ABC transporters have a well-established role in drug resistance, effluxing
      xenobiotics from cells and tissues within the organism. More recently, research
      has been dedicated to understanding the role insect ABC transporters play in
      insecticide toxicity, but progress in understanding the contribution of specific
      transporters has been hampered by the lack of functional genetic tools. Here, we
      report knockouts of three Drosophila melanogaster ABC transporter genes, Mdr49,
      Mdr50, and Mdr65, that are homologous to the well-studied mammalian ABCB1 (P
      glycoprotein). Each knockout mutant was created in the same wild type background
      and tested against a panel of insecticides representing different chemical
      classes. Mdr65 knockouts were more susceptible to all neuroactive insecticides
      tested, but Mdr49 and Mdr50 knockouts showed increased susceptibility or
      resistance depending on the insecticide used. Mdr65 was chosen for further
      analysis. Calculation of LC50 values for the Mdr65 knockout allowed the substrate
      specificity of this transporter to be examined. No obvious distinguishing
      structural features were shared among MDR65 substrates. A role for Mdr65 in
      insecticide transport was confirmed by testing the capacity of the knockout to
      synergize with the ABC inhibitor verapamil and by measuring the levels of
      insecticide retained in the body of knockout flies. These data unambiguously
      establish the influence of ABC transporters on the capacity of wild type D.
      melanogaster to tolerate insecticide exposure and suggest that both tissue and
      substrate specificity underpin this capacity.

PMID- 29056375
TI  - The economic impact of agricultural pollutions in Iran, spatial distance function
      approach.
AB  - Pollution has increased in Iran in the last two decades due to agricultural
      activities. Pollutions are released into the atmosphere and thereafter pollute
      water and soil resources. Therefore, it is important to develop models that can
      estimate the economic value of these Pollutions. For this purpose, a Spatial
      Output Distance Function was used in the present study to estimate the shadow
      price of carbon dioxide emission and water salinity in spatial and temporal
      dimensions. This method can be used as a new method to estimate the value of
      externalities. In this study, the data of provinces in Iran during 1995-2014 were
      used. The results showed that the total shadow price of agricultural Pollutions
      was equal to 42.54 dollars per unit. In addition, the effects due to the
      adjacency of regions to each other led to the transfer of pollution and its
      externalities were equal to 26.3 dollars per unit of pollution. This finding
      refers to the importance of considering the spatial dimension when analyzing the
      shadow price of pollutions caused by production. Thus, internalizing the damage
      caused by pollutions based on the adjacency of regions to each other can increase
      the efficiency of the production environment.

PMID- 29056376
TI  - Toxic effects of multi-walled carbon nanotubes on bivalves: Comparison between
      functionalized and nonfunctionalized nanoparticles.
AB  - Despite of the large array of available carbon nanotube (CNT) configurations that
      allow different industrial and scientific applications of these nanoparticles,
      their impacts on aquatic organisms, especially on invertebrate species, are still
      limited. To our knowledge, no information is available on how surface chemistry
      alteration (functionalization) of CNTs may impact the toxicity of these NPs to
      bivalve species after a chronic exposure. For this reason, the impacts induced by
      chronic exposure (28days) to unfunctionalized MWCNTs (Nf-MWCNTs) in comparison
      with functionalized MWCNTs (f-MWCNTs), were evaluated in R. philippinarum, by
      measuring alterations induced in clams' oxidative status, neurotoxicity and
      metabolic capacity. The results obtained revealed that exposure to both MWCNT
      materials altered energy-related responses, with higher metabolic capacity and
      lower glycogen, protein and lipid concentrations in clams exposed to these CNTs.
      Moreover, R. philippinarum exposed to Nf-MWCNTs and f-MWCNTs showed oxidative
      stress expressed in higher lipid peroxidation and lower ratio between reduced and
      oxidized glutathione, despite the activation of defense mechanisms (superoxide
      dismutase, glutathione peroxidase and glutathione S-transferases) in exposed
      clams. Additionally, neurotoxicity was observed by inhibition of Cholinesterases
      activity in organisms exposed to both MWCNTs.

PMID- 29056377
TI  - A 150-year record of polycyclic aromatic compound (PAC) deposition from high
      Andean Cajas National Park, southern Ecuador.
AB  - The temporal profiles of polycyclic aromatic compounds (PACs) in lake sediments
      reflect past changes in emissions, transport and deposition of these pollutants
      and, thus, record natural and anthropogenic processes. We document fluxes of PACs
      [(polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs (OPAHs) and azaarenes
      (AZAs)] deposited in two tropical high-altitude lakes in the Cajas National Park
      (Ecuadorian Andes, 2 degrees 50'S, 79 degrees 10'W). In remote and high elevation
      Laguna Fondococha (4130m a.s.l.), the temporal fluxes of OPAHs and AZAs were
      similar to those of PAHs suggesting similar sources. A significant increase of
      PAC deposition after the 1950s reflects Ecuador's economic development. PAH
      fluxes were relatively low (?27PAHs (without retene and perylene): 0.86-11.21ngcm
      2yr-1) with a composition pattern typical for long-range atmospheric transport
      (high 9-fluorenone/fluorene ratios) and biomass burning (30% low molecular weight
      PAHs). PAHs diagnostic of high temperature combustion (industry, traffic) make up
      20-25% of total PAHs. Perylene concentrations increase linearly with increasing
      sediment depth suggesting diagenetic in-situ production. At lower elevations
      (Laguna Llaviucu, 3140m a.s.l.) and closer to urban areas, PAC fluxes in the past
      decades were 4-5 times higher than in the remote high-elevation lake. Laguna
      Llaviucu also showed higher concentrations of high molecular weight pyrogenic
      PAHs and a greater diversity of AZAs. Individual OPAHs and AZAs reflect mainly
      combustion activities. In Laguna Llaviucu, which is at a lower elevation (3140m
      a.s.l.) and closer to the city, molecular ratios suggest short-range atmospheric
      transport and deposition of PACs. A very foggy climate (170 rainy days per year)
      with the precipitation maximum at 3500m removes PACs very efficiently (by wet
      deposition) from the atmosphere at very short distances from emission sources.
      This partly explains why L. Llaviucu shows higher fluxes of PACs than the higher
      elevation L. Fondococha. This study presents the first historical record of
      organic pollutants from environmental archives in Ecuador.

PMID- 29056379
TI  - Multi-layered water resources, management, and uses under the impacts of global
      changes in a southern coastal metropolis: When will it be already too late?
      Crossed analysis in Recife, NE Brazil.
AB  - Coastal water resources are a worldwide key socio-environmental issue considering
      the increasing concentration of population in these areas. Here, we propose an
      integrative transdisciplinary approach of water resource, water management and
      water access in Recife (NE Brazil). The present-day water situation is
      conceptualized as an imbricated multi-layered system: a multi-layered water
      resource, managed by a multi-layered governance system and used by a multi
      layered social population. This allows identifying processes of quantitative,
      qualitative, and sanitary conflicts between governance and population strategies
      regarding water supply, as well as the institutional and individual denials of
      these conflicts. Based on this model, we anticipate future water-related
      problematic fates. Concerning the water resource system, the rapid groundwater
      level decrease due to unsustainable water predatory strategies, and the very low
      recharge rate have drastically modified the aquifer system functioning, inducing
      hydraulic connection between shallow groundwater (contaminated and locally salty)
      and deep ones (mostly fresh, with local inherited salinity), threatening the deep
      strategic water resource. Concerning the water governance system, the investments
      to increase the capacity storage of surface water, the water regulation agencies
      and the public/private partnership should shortly improve the water supply and
      wastewater issue. Nevertheless, the water situation will remain highly fragile
      due to the expected water demand increase, the precipitation decrease and the sea
      level increase. Concerning the water access system, the population variably
      perceives these current and further effects and the possible mitigation policies,
      and develops alternative individual strategies. Authorities, policymakers and
      water managers will have to implement a well-balanced water governance, taking
      into account the specificities of the PPP, public and private groundwater users,
      and with a strong political willingness for a sustainable water management to
      ensure water supply for all the population. In other words, an anticipatory and
      integrated vision is necessary to reduce the discrepancies in this complex
      system.

PMID- 29056378
TI  - Use of multi-criteria decision analysis to identify potentially dangerous glacial
      lakes.
AB  - Glacial Lake Outburst Floods (GLOFs) represent a significant threat in
      deglaciating environments, necessitating the development of GLOF hazard and risk
      assessment procedures. Here, we outline a Multi-Criteria Decision Analysis (MCDA)
      approach that can be used to rapidly identify potentially dangerous lakes in
      regions without existing tailored GLOF risk assessments, where a range of glacial
      lake types exist, and where field data are sparse or non-existent. Our MCDA model
      (1) is desk-based and uses freely and widely available data inputs and software,
      and (2) allows the relative risk posed by a range of glacial lake types to be
      assessed simultaneously within any region. A review of the factors that influence
      GLOF risk, combined with the strict rules of criteria selection inherent to MCDA,
      has allowed us to identify 13 exhaustive, non-redundant, and consistent risk
      criteria. We use our MCDA model to assess the risk of 16 extant glacial lakes and
      6 lakes that have already generated GLOFs, and found that our results agree well
      with previous studies. For the first time in GLOF risk assessment, we employed
      sensitivity analyses to test the strength of our model results and assumptions,
      and to identify lakes that are sensitive to the criteria and risk thresholds
      used. A key benefit of the MCDA method is that sensitivity analyses are readily
      undertaken. Overall, these sensitivity analyses lend support to our model,
      although we suggest that further work is required to determine the relative
      importance of assessment criteria, and the thresholds that determine the level of
      risk for each criterion. As a case study, the tested method was then applied to
      25 potentially dangerous lakes in the Bolivian Andes, where GLOF risk is poorly
      understood; 3 lakes are found to pose 'medium' or 'high' risk, and require
      further detailed investigation.

PMID- 29056380
TI  - Association between degradation of pharmaceuticals and endocrine-disrupting
      compounds and microbial communities along a treated wastewater effluent gradient
      in Lake Mead.
AB  - The role of microbial communities in the degradation of trace organic
      contaminants in the environment is little understood. In this study, the
      biotransformation potential of 27 pharmaceuticals and endocrine-disrupting
      compounds was examined in parallel with a characterization of the native
      microbial community in water samples from four sites variously impacted by urban
      run-off and wastewater discharge in Lake Mead, Nevada and Arizona, USA. Samples
      included relatively pristine Colorado River water at the upper end of the lake,
      nearly pure tertiary-treated municipal wastewater entering via the Las Vegas
      Wash, and waters of mixed influence (Las Vegas Bay and Boulder Basin), which
      represented a gradient of treated wastewater effluent impact. Microbial diversity
      analysis based on 16S rRNA gene censuses revealed the community at this site to
      be distinct from the less urban-impacted locations, although all sites were
      similar in overall diversity and richness. Similarly, Biolog EcoPlate assays
      demonstrated that the microbial community at Las Vegas Wash was the most
      metabolically versatile and active. Organic contaminants added as a mixture to
      laboratory microcosms were more rapidly and completely degraded in the most
      wastewater-impacted sites (Las Vegas Wash and Las Vegas Bay), with the majority
      exhibiting shorter half-lives than at the other sites or in a bacteriostatic
      control. Although the reasons for enhanced degradation capacity in the wastewater
      impacted sites remain to be established, these data are consistent with the
      acclimatization of native microorganisms (either through changes in community
      structure or metabolic regulation) to effluent-derived trace contaminants. This
      study suggests that in urban, wastewater-impacted watersheds, prior exposure to
      organic contaminants fundamentally alters the structure and function of microbial
      communities, which in turn translates into greater potential for the natural
      attenuation of these compounds compared to more pristine sites.

PMID- 29056381
TI  - Multivariate geostatistical analysis and source identification of heavy metals in
      the sediment of Poyang Lake in China.
AB  - Heavy metals in lake sediment have become a great concern because their
      remobilization has frequently occurred under hydrodynamic disturbance in shallow
      lakes. In this study, heavy metals (Cr, Cu, Cd, Pb, and Zn) concentrations in the
      surface and core sediments of the largest freshwater lake in China, Poyang Lake,
      were investigated. Geostatistical prediction maps of heavy metals distribution in
      the surface sediment were completed as well as further data mining. Based on the
      prediction maps, the ranges of Cr, Cu, Cd, Pb, and Zn concentrations in the
      surface sediments of the entire lake were 96.2-175.2, 38.3-127.6, 0.2-2.3, 22.5
      77.4, and 72.3-254.4mg/kg, respectively. A self-organizing map (SOM) was applied
      to find the inner element relation of heavy metals in the sediment cores. K-means
      clustering of the self-organizing map was also completed to define the Euclidian
      distance of heavy metals in the sediment cores. The geoaccumulation index (Igeo)
      for Poyang Lake indicated a varying degree of heavy metal contamination in the
      surface sediment, especially for Cu. The heavy metal contamination in the
      sediment profiles had similar pollution levels as those of surface sediment,
      except for Cd. Correlation matrix mapping and principal component analysis (PCA)
      were used to support the idea that Cr, Pb, and Zn may be mainly derived from both
      lithogenic and human activities, such as atmospheric and river inflow
      transportation, whereas Cu and Cd may be mainly contributed from anthropogenic
      sources, such as mining activities and fertilizer application.

PMID- 29056382
TI  - Evaluation of genotoxic potential in the Velika Morava River Basin in vitro and
      in situ.
AB  - The Velika Morava River is the greatest national Serbian river and the
      significant tributary of the Danube River. The major problems in the Velika
      Morava River Basin (VMRB) represent untreated industrial and municipal
      wastewaters. In this study, the level of genotoxic potential at the sites along
      the VMRB was evaluated by parallel in vitro and in situ approach. Within in vitro
      testing, genotoxicity of native water samples collected from the sites in VMRB
      was evaluated by SOS/umuC test on Salmonella typhimurium TA1535/pSK1002 and by
      the comet assay on HepG2 cells. DNA damage in situ was assessed in bleak
      (Alburnus alburnus) erythrocytes by the comet (alkaline and Fpg-modified comet)
      and micronucleus assays. Additionally, the concentration of heavy metals in fish
      tissue was measured and this data, compiled with the data of the physico-chemical
      parameters measured in water, was used as a measure of the pollution pressure at
      the sites. Results showed that applied in vitro tests with native water samples
      are less sensitive in comparison with in situ tests and should be taken with
      precaution when making predictions on the status of the ecosystem. Within applied
      battery of in situ assays differential sensitivity of assays was observed where
      alkaline comet assay showed the highest potential in differentiation of the sites
      based on genotoxic potential. Integrated biomarker response showed that usage of
      the battery of bioassays provides better insight in a genotoxic effects in
      animals, and consequently, that the holistic approach is more suitable for this
      type of study.

PMID- 29056383
TI  - Deglaciation and its impact on permafrost and rock glacier evolution: New insight
      from two adjacent cirques in Austria.
AB  - Glaciers and permafrost are strongly linked to each other in mid-latitude
      mountain regions particularly with polythermal glaciers. This linkage is not only
      climatically defined but also in terms of geomorphic and glaciological processes.
      We studied two adjacent cirques located in the Central Austria. We focussed on
      the deglaciation since the Little Ice Age (LIA) maximum (c.1850CE) and its
      relevance for permafrost and rock glacier evolution since then. One cirque is
      occupied by a glacier remnant whereas the second one is occupied by an active
      rock glacier which was partly overridden by a glacier during the LIA. We applied
      a multidisciplinary approach using field-based techniques including geoelectrics,
      geodetic measurements, and automatic monitoring as well as historic maps and
      photographs, remote sensing, and digital terrain analysis. Results indicate
      almost complete deglaciation by the end of the last millennium. Small-scale
      tongue-shaped landforms of complex origin formed during the last decades at finer
      grained slope deposits below the cirque headwalls. Field evidences and geophysics
      results proved the existence of widespread sedimentary ice beneath a thin veneer
      of debris at these slopes. The variable thickness of the debris layer has a major
      impact on differential ablation and landform evolution in both cirques. The
      comparison of digital elevation models revealed clear mass losses at both cirques
      with low rates between 1954 and 2002 and significantly higher rates since then.
      The central and lower part of the rock glacier moves fast transporting sediments
      and ice downvalley. In contrast, the upper part of the rock glacier is
      characterised by low debris and ice input rates. Both effects cause a significant
      decoupling of the main rock glacier body from its nourishment area leading
      eventually to rock glacier starvation. This study demonstrates the importance of
      a decadal-scale and multidisciplinary research approach in determining the
      development of alpine landforms over both space and time.

PMID- 29056384
TI  - Different methods of incorporating ciprofloxacin in soil affect microbiome and
      degradation of ciprofloxacin residue.
AB  - Antibiotic residues in swine manure when entered the soil would most likely
      affect the complex composition and functions of the soil microbiome, which is
      also responsible for degrading these antibiotics. Three different methods of
      adding ciprofloxacin (CIP), a common antibiotic used in the swine industry, to
      the soil were used to investigate the effects of CIP on the soil microbiome and
      the degradation of CIP. Results of the study showed that the microbiome could
      promote the degradation of CIP in the soil when CIP was incorporated into the
      soil together with manure. However, the CIP degradation time was prolonged when
      adding the manure of swine fed with diet containing CIP in the soil. All
      treatments did not affect the copy number of the resistance genes, except for
      aac(6')-Ib-cr, as compared with the initial numbers of each treatment. MiSeq
      Illumina sequencing and Biolog-ECO microplates results showed that CIP had a
      significant effect on the abundance, structure, and function of the soil
      microbiome, but different addition methods resulted in distinct effects. Results
      of the present study demonstrated that the microbiome and fate of CIP responded
      differently to the different methods of adding CIP to the soil.

PMID- 29056385
TI  - Research and application of non-traditional chemical stabilizers on bauxite
      residue (red sand) dust control, a review.
AB  - Bauxite residue is a by-product of aluminium processing. It is usually stored in
      large-scale residue drying area (RDA). The bauxite residue is highly alkaline and
      contains a large percentage of metal oxides which are hazardous to the
      environment and human health. Therefore, the generated dust is a major
      environmental concern that needs to be addressed and efficiently managed. One of
      the major dust generation sources is from the coarse fraction of the bauxite
      residue named red sand. To minimize the environmental and health impacts, non
      traditional chemical stabilizers can be applied to construct a binding surface
      crust with certain hardness and strength. Dust emission is reduced due to the
      increased moisture retention capacity and strong cohesion between sand particles.
      There are limited number of refereed publications that discuss the application of
      this method to alleviate dust generation from red sand. By critically reviewing
      the literature and the application of non-traditional chemical stabilizers to
      sand-like materials in other fields, this paper introduces some non-traditional
      chemical stabilizers that can be potentially used for controlling red sand dust.
      Commonly used evaluation methods in various studies are compared and summarized;
      the stabilization mechanisms are examined; and the performance of three types of
      stabilizers are compared and evaluated. This review potentially serves as a
      reference and guide for further studies in red sand dust control. The findings
      are especially useful for developing suitable quantitative methods for evaluating
      the dust suppression efficiency of soil stabilizers, and for determining the
      appropriate additive quantities that achieve both economic and performance
      effectiveness.

PMID- 29056386
TI  - In vitro prediction of polycyclic aromatic hydrocarbon bioavailability of 14
      different incidentally ingested soils in juvenile swine.
AB  - Predicting mammalian bioavailability of PAH mixtures from in vitro
      bioaccessibility results has proven to be an elusive goal. In an attempt to
      improve in vitro predictions of PAH soil bioavailability we investigated how
      energetic input influences PAH bioaccessibility by using a high and low energetic
      shaking method. Co-inertia analysis (COIA), and Structural Equation Modeling
      (SEM) were also used to examine PAH-PAH interactions during ingestion. PAH
      bioaccessibility was determined from 14 historically contaminated soils using the
      fed organic estimation of the human simulation test (FOREhST) with inclusion of a
      silicone rod as a sorption sink and compared to bioavailability estimates from
      the juvenile swine model. Shaking method significantly affected PAH
      bioaccessibility in the FOREhST model, with PAH desorption from the high energy
      FOREhST almost an order of magnitude greater compared to the low energy FOREhST.
      PAH-PAH interactions significantly influenced PAH bioavailability and when these
      interactions were used in a linear model, the model predicted benzo(a)anthracene
      bioavailability with an slope of 1 and r2 of 0.66 and for benzo(a)pyrene
      bioavailability has a slope of 1 and r2 of 0.65. Lastly, to confirm the effects
      as determined by COIA and SEM, we spiked low levels of benzo(a)anthracene into
      historically contaminated soils, and observed a significant increase in
      benzo(a)pyrene bioaccessibility. By accounting for PAH interactions, and reducing
      the energetics of in vitro extractions, we were able to use bioaccessibility to
      predict bioavailability across 14 historically contaminated soils. Our work
      suggests that future work on PAH bioavailability and bioaccessibility should
      focus on the dynamics of how the matrix of PAHs present in the soil interact with
      mammalian systems. Such interactions should not only include the chemical
      interactions discussed here but also the interactions of PAH mixtures with
      mammalian uptake systems.

PMID- 29056387
TI  - Partitioning multi-source uncertainties in simulating nitrogen loading in stream
      water using a coherent, stochastic framework: Application to a rice agricultural
      watershed in subtropical China.
AB  - Uncertainty is recognized as a critical consideration for accurately predicting
      stream water nitrogen (N) loading, but identifying the relative contribution of
      individual uncertainty sources within the total uncertainty remains unclear. In
      this study, a powerful method, referred to as the Bayesian inference combined
      with analysis of variance (BayeANOVA) was adopted to detect the timing and
      magnitude of multiple uncertainty sources and their relative contributions to
      total uncertainty in simulating daily loadings of three stream water N species
      (ammonium-N: NH4+-N, nitrate-N: NO3--N and total N: TN) in a rice agricultural
      watershed (the Tuojia watershed) as influenced by non-point source N pollution.
      Five sources of uncertainty have been analyzed in this study, which arise from
      model structure, parameters, inputs, interaction effects between parameters and
      inputs, and internal variability (induced by random errors of model or
      environment). The results show that uncertainty in parameters relating to the
      processes of both N and hydrologic cycles contributed the largest fractions of
      total uncertainty in N loading simulations (58.83%, 63.48% and 61.64% for NH4+-N,
      NO3--N and TN loading, respectively). Additionally, three of the largest
      uncertainties (i.e. parameters, inputs and interaction effects) in all three
      simulated N loadings were on average significantly greater in the rice-growing
      season relative to the fallow season, primarily due to the excess fertilization
      application during the rice-growing season. The predicted TN uncertainty was
      mainly attributed to the inaccuracy of NO3--N simulation, which contributed to
      75.48% of predicted TN uncertainty. It is concluded that reducing the parameter
      uncertainty of NO3--N loading simulation during the rice-growing season is the
      key factor to improving stream water N modeling precision in rice agricultural
      watersheds.

PMID- 29056389
TI  - Differences in the sensitivity to Cu and ligand production of coastal vs offshore
      strains of Emiliania huxleyi.
AB  - Copper is an essential trace metal for different physiological processes in
      phytoplankton, being either a limiting or toxic element depending on its
      bioavailability, which may induce local physiological adaptations. Atmospheric Cu
      deposition to the oceans can negatively impact phytoplankton growth, with the
      most Cu-sensitive phytoplankton exhibiting differences based on coastal vs
      oceanic origin. The goal of this work was to analyze sensitivity to Cu toxicity
      of the cosmopolitan marine calcifying phytoplankton, Emiliania huxleyi, exploring
      what factors determine intraspecific variability in sensitivity. We compared 17
      strains isolated from coastal and open ocean waters of the Eastern South Pacific
      (ESP), the Mediterranean Sea, and the Tasman Sea. Offshore strains were as
      sensitive to Cu than coastal strains. Sensitivity to Cu was explained well by
      predicted depositional inputs of atmospheric Cu in the ESP both for coastal and
      offshore strains, but not when considered globally. The variability in Cu
      sensitivity was also due to the production of organic Cu-ligands (CL), being the
      most productive strains the most tolerant to Cu at constitutive levels. When
      exposed to 100nM Cu, E. huxleyi produced significantly higher amounts of CL,
      especially coastal strains, but CL production did not correlate to observed
      EC50s.

PMID- 29056388
TI  - Aqueous Hg(II) immobilization by chitosan stabilized magnetic iron sulfide
      nanoparticles.
AB  - Stabilized iron sulfide (FeS) nanoparticles have been proven effective in the
      adsorption of Hg from the water environment. However, previous work with these
      nanoparticles determined that the separation from the treated water was difficult
      and time-consuming. In this study, nanoscale FeS-Fe3O4 nanocomposites were
      firstly synthesized with chitosan as the stabilizer (CTO-MFeS). Then, the Hg
      adsorption capacity and mechanism were studied. Results showed that the size of
      the prepared nanoparticles was about 20nm and the specific surface area was
      21.3m2/g. Hg removal by the CTO-MFeS nanoparticles involved both adsorption and
      precipitation. Further investigation with XPS showed that Hg2+ was adsorbed on
      the surface of the CTO-MFeS nanoparticles and reacted with CTO-MFeS to form HgS
      and [Fe(1-x)Hgx]S. It was also found as pH decreased below 4, the adsorption
      capacity of CTO-MFeS was significantly reduced that might be due to the
      dissolving of Fe. Additionally, the presence of Cl- resulted in the
      transformation of Hg2+ to HgClx2-x (x=1, 2, 3, 4) that competed with OH in
      solution for Hg2+ and therefore inhibited the adsorption of Hg. Our findings
      provide additional information that may be useful for a theoretical basis for Hg
      treatment in water environment.

PMID- 29056390
TI  - Atypically localized glomus tumor causing anterior interosseous nerve syndrome: A
      case report.
AB  - This article presents a 48-year-old male patient who presented with pain in the
      left forearm and weakness and clumsiness in the left hand of 6 months' duration.
      Flexor motor strength loss of the thumb and the index finger was present and
      neurophysiologic tests showed findings compatible with axonal injury in the
      anterior interosseous nerve (AIN) innervated muscles. Magnetic resonance imaging
      revealed a space-occupying lesion in the proximal forearm resembling a glomus
      tumor. Excision of the mass and release of the AIN were performed. Histopathology
      confirmed a glomus tumor, and the patient remains asymptomatic at 1 year
      postoperatively. We stress the importance of imaging studies in patients when a
      suspected secondary nature of nerve entrapment is present.

PMID- 29056391
TI  - Prehospital triage of septic patients at the SAMU regulation: Comparison of
      qSOFA, MRST, MEWS and PRESEP scores.
AB  - PURPOSE: A couple of scoring systems have been developed for risk stratification
      of septic patients. Their performance in the management of out-of-hospital
      initial care delivery is not documented. This study try to evaluate the
      predictive ability of Quick Sequential Organ Failure Assessment (qSOFA), Robson
      Screening Tool (RST), Modified Early Warning Score (MEWS) and Prehospital Early
      Sepsis Detection (PRESEP) scores on out of-hospital triage of septic patients, to
      predict intensive care unit (ICU) admission. METHODS: A retrospective study using
      call records received by the SAMU 15 regulation call centre including all
      patients with presumed septic shock was performed. The primary outcome was the
      admission to the ICU. RESULTS: Among the 47 000 reports received, 37 patients
      with presumed septic shock were included. Twenty-two patients (59%) were admitted
      to ICU. AUCs of qSOFA, RST, MEWS and PRESEP scores were respectively 0.40 [0.22
      0.59], 0.60 [0.43-0.78], 0.66 [0.47-0.85] and 0.67 [0.51-0.84]. RST outperformed
      PRESEP, MEWS and qSOFA for sensitivity (1, 0.92, 0.85 and 0.62 respectively).
      MEWS showed better specificity than PRESEP, MRST and qSOFA (0.33, 0.29, 0.16 and
      0.16). MEWS showed comparable positive predictive value than PRESEP and
      outperformed MRST and qSOFA (0.41, 0.41, 0.39 and 0.29 respectively). Negative
      predictive value of MRST outperformed PRESEP, MEWS and qSOFA (1, 0.88, 0.80 and
      0.44 respectively). CONCLUSION: Our findings suggest that screening patients at
      SAMU 15 regulation call centre using qSOFA, MRST, MEWS and PRESEP scores to
      predict ICU admission is irrelevant. Development of a specific scoring system for
      out-of-hospital triage of septic patients is needed.

PMID- 29056392
TI  - Resuscitation quality of rotating chest compression providers at one-minute vs.
      two-minute intervals: A mannequin study.
AB  - OBJECTIVE: The aim of this randomized cross-over study was to compare one-minute
      and two-minute continuous chest compressions in terms of chest compression only
      CPR quality metrics on a mannequin model in the ED. MATERIALS AND METHODS: Thirty
      six emergency medicine residents participated in this study. In the 1-minute
      group, there was no statistically significant difference in the mean compression
      rate (p=0.83), mean compression depth (p=0.61), good compressions (p=0.31), the
      percentage of complete release (p=0.07), adequate compression depth (p=0.11) or
      the percentage of good rate (p=51) over the four-minute time period. Only flow
      time was statistically significant among the 1-minute intervals (p<0.001). In the
      2-minute group, the mean compression depth (p=0.19), good compression (p=0.92),
      the percentage of complete release (p=0.28), adequate compression depth (p=0.96),
      and the percentage of good rate (p=0.09) were not statistically significant over
      time. In this group, the number of compressions (248+/-31 vs 253+/-33, p=0.01)
      and mean compression rates (123+/-15 vs 126+/-17, p=0.01) and flow time (p=0.001)
      were statistically significant along the two-minute intervals. There was no
      statistically significant difference in the mean number of chest compressions per
      minute, mean chest compression depth, the percentage of good compressions,
      complete release, adequate chest compression depth and percentage of good
      compression between the 1-minute and 2-minute groups. CONCLUSION: There was no
      statistically significant difference in the quality metrics of chest compressions
      between 1- and 2-minute chest compression only groups.

PMID- 29056393
TI  - Blood sugar changes and hospital mortality in multiple trauma.
AB  - OBJECTIVES: Hyperglycemia with unknown mechanism plays a predictive role in
      determining the prognosis of multiple trauma patients. The exact time of blood
      sugar measurement and the role of blood sugar changes in the monitoring of these
      patients have not been well established. METHODS: This follow-up study was done
      on multiple trauma patients (>18years) with an Injury Severity Scores (ISS)>16.
      These patients didn't have any history of diabetes, underlying disease, or drug
      or alcohol use. Data collection was done by the questionnaire (checklist), and
      the patients were followed by the medical records. Cox regression was used to
      measure the effect of independent variables on the patients' hospital mortality.
      RESULTS: Of a total of 963 patients, 280 patients were enrolled. Of those, 202
      were male (72.1%) and 78 were female (27.9%). Hospital mortality was 18 (6.4%).
      Cox regression analysis suggested that those who had high blood sugar 3h after
      admission had higher hospital mortality (P=0.04). Changes in blood sugar, DeltaBS
      (BS 3h after admission - BS on admission), in these patients was also
      significantly correlated with hospital mortality (P<0.001). The multivariate
      model using the backward conditional method showed that DeltaBS (P<0.001),
      international normalized ration (INR) (P<0.001), and heart rate (P=0.036) were
      significantly correlated with hospital mortality. CONCLUSIONS: In multiple trauma
      patients, blood sugar changes in the early hours of admission to the emergency
      department may help predict hospital mortality, but further studies are needed.
      Blood sugar monitoring in these patients during this time frame may be helpful in
      predicting these patients' outcomes. In addition, coagulopathy and tachycardia
      were significantly associated with hospital mortality.

PMID- 29056394
TI  - STrategically Acquired Gradient Echo (STAGE) imaging, part I: Creating enhanced
      T1 contrast and standardized susceptibility weighted imaging and quantitative
      susceptibility mapping.
AB  - PURPOSE: To provide whole brain grey matter (GM) to white matter (WM) contrast
      enhanced T1W (T1WE) images, multi-echo quantitative susceptibility mapping (QSM),
      proton density (PD) weighted images, T1 maps, PD maps, susceptibility weighted
      imaging (SWI), and R2* maps with minimal misregistration in scanning times <5min.
      METHODS: Strategically acquired gradient echo (STAGE) imaging includes two fully
      flow compensated double echo gradient echo acquisitions with a resolution of
      0.67*1.33*2.0mm3 acquired in 5min for 64 slices. Ten subjects were recruited and
      scanned at 3 Tesla. The optimum pair of flip angles (6 degrees  and 24 degrees 
      with TR=25ms at 3T) were used for both T1 mapping with radio frequency (RF)
      transmit field correction and creating enhanced GM/WM contrast (the T1WE). The
      proposed T1WE image was created from a combination of the proton density weighted
      (6 degrees , PDW) and T1W (24 degrees ) images and corrected for RF transmit
      field variations. Prior to the QSM calculation, a multi-echo phase unwrapping
      strategy was implemented using the unwrapped short echo to unwrap the longer echo
      to speed up computation. R2* maps were used to mask deep grey matter and veins
      during the iterative QSM calculation. A weighted-average sum of susceptibility
      maps was generated to increase the signal-to-noise ratio (SNR) and the contrast
      to-noise ratio (CNR). RESULTS: The proposed T1WE image has a significantly
      improved CNR both for WM to deep GM and WM to cortical GM compared to the
      acquired T1W image (the first echo of 24 degrees  scan) and the T1MPRAGE image.
      The weighted-average susceptibility maps have 80+/-26%, 55+/-22%, 108+/-33% SNR
      increases across the ten subjects compared to the single echo result of 17.5ms
      for the putamen, caudate nucleus, and globus pallidus, respectively. CONCLUSIONS:
      STAGE imaging offers the potential to create a standardized brain imaging
      protocol providing four pieces of quantitative tissue property information and
      multiple types of qualitative information in just 5min.

PMID- 29056395
TI  - 3D transesophageal echocardiography: A new imaging tool for assessment of mitral
      regurgitation and for guiding percutaneous edge-to-edge mitral valve repair.
AB  - Real time three dimensional transesophageal echocardiography (3D TEE) is probably
      the most powerful and convincing imaging method for understanding the complicated
      multiform morphology and for evaluating geometry, dynamics and function of
      degenerative and functional mitral valve (MV) regurgitation. Moreover, color
      Doppler 3D TEE has been valuable to identify the location of the regurgitant
      orifice and the severity of the mitral regurgitation. 3D TEE has been shown to be
      of enormous value in helping surgeons to perform MV repair. In addition, due to
      its ability to show a "panoramic" view of the "theater" where the procedure takes
      place, it has become an indispensable companion of 2D TEE during percutaneous
      edge-to-edge repair. A novel hybrid imaging modality where echocardiography is
      merged with fluoroscopy, may in the future further improve guidance of this and
      other complex percutaneous transcatheter interventions.

PMID- 29056396
TI  - Serology in autoimmune hepatitis: A clinical-practice approach.
AB  - Serology is key to the diagnosis of autoimmune hepatitis (AIH). Clinicians need
      to be aware of which tests to request, how to interpret the laboratory reports,
      and be familiar with the laboratory methodology. If correctly tested, >95% of AIH
      patients show some serological reactivity. Indirect immunofluorescence on triple
      rodent tissue is recommended as first screening step, since it allows the
      detection of all liver-relevant autoantibodies, except for anti-soluble liver
      antigen (SLA) antibody, which needs to be detected by molecular based assays. The
      threshold of immunofluorescence positivity is a titer equal or exceeding 1/40,
      but for patients younger than 18years even lower titers are clinically
      significant. Anti-nuclear antibody (ANA) and/or anti-smooth muscle (SMA) antibody
      characterize type 1 AIH. ANA in AIH typically shows a homogeneous staining
      pattern on HEp2 cells, without any specific target antigen. Anti-SMA displays
      different staining patterns on indirect immunofluorescence: the
      vascular/glomerular (VG) and the vascular/glomerular/tubular (VGT) patterns are
      considered specific for AIH, whilst the V pattern can be found in a variety of
      diseases. Type 2 AIH, which is rare and affects mostly children/adolescents, is
      characterized by anti-liver kidney microsomal 1 and/or anti-liver cytosol 1
      antibodies. The presence of anti-neutrophil cytoplasmic antibody (ANCA),
      particularly atypical p-ANCA (pANNA), points to the diagnosis of AIH, especially
      in absence of other autoantibodies. Since it is associated with sclerosing
      cholangitis and inflammatory bowel disease, these conditions have to be ruled
      out. The only antibody specific for AIH is anti-SLA, which is associated with a
      more severe disease course.

PMID- 29056397
TI  - An Update on Cerebrovascular Disease in Dogs and Cats.
AB  - This article reviews definitions and normal anatomy and physiology of canine and
      feline cerebral vasculature. The pathophysiology of cerebrovascular disease
      (CVD), which results from disturbance of cerebral blood supply, is described,
      along with its common causes and correlative findings. The general clinical
      presentation of companion animals is described, although specific neurologic
      abnormalities depend on the neuroanatomic location of the disrupted blood supply.
      Current and future diagnostic approaches are described, including ancillary
      testing for predisposing factors. Acute and chronic management of patients with
      CVD is discussed. The prognosis for dogs and cats with acute CVD is generally
      considered good.

PMID- 29056398
TI  - Transsphenoidal Surgery for Pituitary Tumors and Other Sellar Masses.
AB  - Transsphenoidal surgery is an option for dogs and cats with functional and
      nonfunctional pituitary masses or other sellar and parasellar masses. An
      adrenocorticotropic hormone-secreting tumor causing Cushing disease is the most
      common clinically relevant pituitary tumor in dogs, and the most common pituitary
      tumor seen in cats is a growth hormone-secreting tumor causing acromegaly.
      Transsphenoidal surgery can lead to rapid resolution of clinical signs and
      provide a cure for these patients. Because of the risks associated with this
      surgery, it should only be attempted by a cohesive pituitary surgery group with a
      sophisticated medical and surgical team.

PMID- 29056399
TI  - Targeting Cholesterol in Non-ischemic Heart Failure: A Role for LDLR Gene
      Therapy?

PMID- 29056400
TI  - Social Media Utilization at an Academic Radiology Practice.
AB  - RATIONALE AND OBJECTIVES: We report social media (SoMe) utilization trends at an
      academic radiology department, highlighting differences between trainees and
      faculty and between Baby Boomers versus Generation X and Millennials. MATERIALS
      AND METHODS: An anonymous online survey regarding SoMe utilization and SoMe-based
      educational curriculum was distributed to all radiologists (trainees and faculty)
      in our department. Regular chi-square, ordered (Mantel-Haenszel) chi-square, and
      Fischer exact tests were performed. RESULTS: The survey instrument was sent to
      172 radiologists with a 65% completion rate (N = 112). Eighty-three percent (n =
      92) of the respondents use SoMe, with Facebook (67%, n = 75), YouTube (57%, n =
      64), Instagram (26%, n = 29), and Twitter (21%, n = 23) as the most commonly used
      platforms. Eighty-one percent (n = 91) use SoMe for 30 minutes or less per day.
      Thirty-five percent (n = 39) reported previously using SoMe for educational
      purposes, although 66% (n = 73) would be willing to join SoMe for educational
      activities. The faculty are more likely than trainees to avoid using SoMe (30% vs
      9%, P < 0.03). Trainees are more likely than faculty to find an electronic case
      based curriculum valuable (95% vs 83%, P < 0.05) and are willing to spend more
      time on cases (P < 0.01). Baby Boomers are less interested in joining SoMe for
      educational activities than Generation X and Millennials (24% vs 73%, P =
      0.0001). CONCLUSIONS: Generation gaps between trainees and faculty, as well as
      between Generation X and Millennials versus Baby Boomers, exist with regard to
      the use of SoMe, which may be underutilized in radiology education.

PMID- 29056401
TI  - Outcomes of Transcatheter Arterial Embolization with a Modified N-Butyl
      Cyanoacrylate Glue for Spontaneous Iliopsoas and Rectus Sheath Hematomas in
      Anticoagulated Patients.
AB  - PURPOSE: To assess the efficacy and safety of n-butyl cyanoacrylate methacryloxy
      sulfolane (NBCA-MS) transcatheter arterial embolization for anticoagulation
      related soft-tissue bleeding and to evaluate predictive factors of clinical
      success and 30-day mortality. MATERIALS AND METHODS: A retrospective review of 50
      anticoagulated patients (25 male; mean age, 71.7 y +/- 14.2; range, 19-87 y) who
      underwent emergent Glubran 2 NBCA-MS embolization for iliopsoas hematomas (IPHs;
      n = 38), rectus sheath hematomas (n = 11), or both (n = 1) between 2011 and 2016
      was performed. Inclusion criteria were active bleeding on computed tomography
      (CT) and anticoagulation. The mean number of red blood cell (RBC) units
      transfused was 4.8 +/- 3.2 (range, 0-14), median hemoglobin level before
      embolization was 9.7 g/dL (range, 6.2-18 g/dL), and median "mean blood pressure"
      (MBP) was 62.5 mm Hg (range, 58.3-75 mm Hg). Mean International Normalized Ratio
      before intervention was 2.5 +/- 1.5 (range, 1.0-6.9). Angiograms revealed
      extravasation in 44 of 50 patients (88%). Mean hematoma volume was 1,119.2 cm3 +/
      863.5 (range, 134.0-3,589.0 cm3). RESULTS: Technical success was achieved in
      100% of patients, and 30-day clinical success was achieved in 66% of patients.
      Recurrent bleeding and mortality rates within 30 days of embolization were 34%
      and 44%, respectively. No complications related to the embolization procedure
      occurred. Lower MBP (P = .003), greater number of RBC units transfused (P =
      .003), greater volume of hematoma (P = .04), and IPH location (P = .02) were
      associated with decreased clinical success. Clinical failure (P = .00002), lower
      MBP (P = .004), greater number of RBC units transfused (P = .002), and IPH
      location (P = .01) were significantly associated with higher 30-day mortality
      rates. CONCLUSIONS: Transcatheter arterial embolization with NBCA-MS is safe and
      effective in treating refractory soft-tissue bleeding in anticoagulated patients
      despite the high mortality rates associated with this patient population.

PMID- 29056402
TI  - Do Fathers' Home Reading Practices at Age 2 Predict Child Language and Literacy
      at Age 4?
AB  - BACKGROUND: Maternal shared reading practices predict emergent literacy, but
      fathers' contributions are less certain. We examined whether fathers' shared home
      reading activities at 2 years predict language and emergent literacy at age 4
      years, when controlling for maternal contributions; and whether this
      differentially benefits these outcomes in disadvantaged children. METHODS: Two
      parent families were recruited from 5 relatively disadvantaged communities for
      the universal Let's Read literacy promotion population-based trial (ISRCTN
      04602902) in Melbourne, Australia. For exposure at 2 years, home reading
      practices were recorded via self-reported maternal and paternal StimQ-Toddler
      questionnaires and dichotomized at study median (high vs low). At 4 years,
      outcomes assessed included receptive and expressive language (Clinical Evaluation
      of Language Fundamentals 4) and emergent literacy (Sunderland Phonological
      Awareness Test-Revised). Linear regression, adjusted for mothers' home reading,
      was performed to assess 2-year-old vocabulary and communication skills and family
      disadvantage. Interaction of disadvantage (yes vs no) with high home reading by
      fathers and at least one parent was assessed. RESULTS: Data were available for
      405 families (64.3%). High father reading at 2 years (reference: low) predicted
      better expressive (mean difference, 4.7; 95% confidence interval, 1.5 to 8.0) and
      receptive (mean difference, 5.0; 95% confidence interval, 1.8 to 8.2) language at
      4 years (both P < .001), but not emergent literacy skills. Similar patterns were
      observed in families with at least one parent with high home reading. Fathers'
      reading did not differentially benefit outcomes in disadvantaged children.
      CONCLUSIONS: Fathers' involvement in reading at 2 years predicted better language
      but not emergent literacy at 4 years, and it did not protect against adverse
      effects of socioeconomic disadvantage.

PMID- 29056403
TI  - A non-destructive method for quality control of the pellet distribution within a
      MUPS tablet by terahertz pulsed imaging.
AB  - Terahertz pulsed imaging (TPI) was applied to analyse the inner structure of
      multiple unit pellet system (MUPS) tablets. MUPS tablets containing different
      amounts of theophylline pellets coated with Eudragit(r) NE 30 D and with
      microcrystalline cellulose (MCC) as cushioning agent were analysed. The tablets
      were imaged by TPI and the results were compared to X-ray microtomography. The
      terahertz pulse beam propagates through the tablets and is back-reflected at the
      interface between the MCC matrix and the coated pellets within the tablet causing
      a peak in the terahertz waveform. Cross-section images of the tablets were
      extracted at different depths and parallel to the tablet faces from 3D terahertz
      data to visualise the surface-near structure of the MUPS tablets. The images of
      the surface-near structure of the MUPS tablets were compared to X-ray
      microtomography images at the same depths. The surface-near structure could be
      clearly resolved by TPI at depths between 24 and 152MUm below the tablet surface.
      An increasing amount of pellets within the MUPS tablets appears to slightly
      decrease the detectability of the pellets within the tablets by TPI. TPI was
      shown to be a non-destructive method for the detection of pellets within the
      tablets and could resolve structures thicker than 30MUm. In conclusion, a proof
      of-concept was provided for TPI as a method of quality control for MUPS tablets.

PMID- 29056404
TI  - Changes in Transcranial Doppler Flow Velocities in Children with Sickle Cell
      Disease: The Impact of Hydroxyurea Therapy.
AB  - BACKGROUND AND OBJECTIVES: Hydroxyurea (HU) was recently described as a
      substitute for chronic transfusion for children with sickle cell disease (SCD)
      and abnormal transcranial Doppler (TCD) velocities who have received at least 1
      year of transfusions. However, the role of HU in reverting elevated TCD
      velocities in patients not treated with transfusion is still debatable. The
      objective of the study was to examine whether HU influences the progression of
      TCD velocities in children with SCD. PATIENTS AND METHODS: Children with SCD with
      at least 2 TCDs not less than 6 months apart were evaluated over 51 months. Time
      averaged maximum mean (TAMM) velocities for the initial and the last transcranial
      Doppler examinations were noted and differences compared between HU and HU-naive
      groups. RESULTS: Overall, 68.8% of the HU-group with elevated TCD velocities
      compared with 40.0% of the HU-naive experienced TCD reversal (P = .047). A higher
      proportion of the HU-naive group, 7 (14.3%) versus 9.8% of the HU group
      experienced TCD conversion. Those with initial conditional velocities in the HU
      group experienced a significant reduction in TAMM velocities (from 176.8 +/- 5.3
      to 162.7 +/- 13.9 cm/s, difference of 14.1 cm/s; P = .001) unlike those in the HU
      naive group (176.3 +/- 5.3 to 170.0 +/- 18.6 cm/s, difference of 6.3 cm/s; P =
      .148). The change in the TAMM velocities was also significantly higher among the
      HU-group (14.1 +/- 12.4 cm/s versus 6.3 +/- 18.5 cm/s, P = .015). CONCLUSION: Our
      data suggest a beneficial role of HU in TCD velocity reduction in patients not
      treated with chronic transfusions, particularly among those with initial
      conditional TCD velocities.

PMID- 29056406
TI  - Smoking, Hypertension, and Their Combined Effect on Ischemic Stroke Incidence: A
      Prospective Study among Inner Mongolians in China: Methodological and Statistical
      Issues.

PMID- 29056405
TI  - Concomitant Asymptomatic Intracranial Atherosclerotic Stenosis Increase the 30
      Day Risk of Stroke in Patients Undergoing Symptomatic Intracranial
      Atherosclerotic Stenosis Stenting.
AB  - BACKGROUND: In the Stenting and Aggressive Medical Management for Preventing
      Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic
      strokes occurred out of the territory of previously symptomatic stenosis during
      the mean follow-up period of 23.4 months. However, it is unknown how many
      ischemic strokes were due to a previously asymptomatic intracranial
      atherosclerotic stenosis (ICAS). The objective of this study was to investigate
      whether the concomitant asymptomatic ICAS influences the outcome of patients
      undergoing symptomatic ICAS stenting. METHODS: We retrospectively reviewed 576
      consecutive patients with nondisabling ischemic stroke (modified Rankin scale
      score of <=3) who were treated with symptomatic ICAS (>=70% stenosis) stenting
      with or without concomitant asymptomatic ICAS. The baseline characteristics and
      the 30-day primary end points (stroke or death after stenting) were compared by
      bivariate and multivariable logistic analyses. RESULTS: The 30-day rate of
      primary end points was 5.2%, which was higher in patients with concomitant
      asymptomatic ICAS (>=50% stenosis) than in those without asymptomatic ICAS (no
      stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with
      concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the
      territory of the stented artery, whereas in patients without asymptomatic ICAS,
      no ischemic stroke occurred out of the territory of the stented artery.
      Multivariable analysis showed that concomitant asymptomatic ICAS was an
      independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence
      interval, 1.14-5.63; P = .023). CONCLUSIONS: Concomitant asymptomatic ICAS (>=50%
      stenosis) might increase the 30-day risk of stroke in patients undergoing
      symptomatic ICAS stenting.

PMID- 29056407
TI  - Diagnostic Accuracy of Echocardiography in ALCAPA: Is It Always Correct to Rely
      Only on Echocardiography? The Issue of False Negatives.

PMID- 29056408
TI  - Effect of Gravitational Gradients on Cardiac Filling and Performance.
AB  - BACKGROUND: Gravity affects every aspect of cardiac performance. When
      gravitational gradients are at their greatest on Earth (i.e., during upright
      posture), orthostatic intolerance may ensue and is a common clinical problem that
      appears to be exacerbated by the adaptation to spaceflight. We sought to
      elucidate the alterations in cardiac performance during preload reduction with
      progressive upright tilt that are relevant both for space exploration and the
      upright posture, particularly the preload dependence of various parameters of
      cardiovascular performance. METHODS: This was a prospective observational study
      with tilt-induced hydrostatic stress. Echocardiographic images were recorded at
      four different tilt angles in 13 astronauts, to mimic varying degrees of
      gravitational stress: 0 degrees  (supine, simulating microgravity of space), 22
      degrees  head-up tilt (0.38 G, simulating Martian gravity), 41 degrees  (0.66 G,
      simulating approximate G load of a planetary lander), and 80 degrees  (1 G,
      effectively full Earth gravity). These images were then analyzed offline to
      assess the effects of preload reduction on anatomical and functional parameters.
      RESULTS: Although three-dimensional end-diastolic, end-systolic, and stroke
      volumes were significantly reduced during tilting, ejection fractions showed no
      significant change. Mitral annular e' and a' velocities were reduced with
      increasing gravitational load (P < .001 and P = .001), although s' was not
      altered. Global longitudinal strain (GLS; from -19.8% +/- 2.2% to -14.7% +/-
      1.5%) and global circumferential strain (GCS; from -29.2% +/- 2.5% to -26.0% +/-
      1.8%) were reduced significantly with increasing gravitational stress (both P <
      .001), while the change in strain rates were less certain: GLSR (P = .049); GCSR
      (P = .55). End-systolic elastance was not consistently changed (P = .53), while
      markers of cardiac afterload rose significantly (effective arterial elastance, P
      < .001; systemic vascular resistance, P < .001). CONCLUSIONS: Preload
      modification with gravitational loading alters most hemodynamic and
      echocardiographic parameters including e' velocity, GLS, and GCS. However, end
      systolic elastance and strain rate appear to be more load-independent measures to
      examine alterations in the cardiovascular function during postural and preload
      changes, including microgravity.

PMID- 29056409
TI  - Pollution, health, and the planet: time for decisive action.

PMID- 29056411
TI  - Towards a healthier and safer environment.

PMID- 29056412
TI  - Mathuros Ruchirawat: leading light in pollution control.

PMID- 29056410
TI  - The Lancet Commission on pollution and health.

PMID- 29056413
TI  - Junior hospital doctors-time to rethink the terminology.

PMID- 29056415
TI  - Is exercise a viable therapeutic intervention to mitigate mitochondrial
      dysfunction and insulin resistance induced by sleep loss?
AB  - Sleep loss has emerged as a risk factor comparable to that of physical inactivity
      for the development of insulin resistance, impaired glucose tolerance and type 2
      diabetes mellitus. This is a concern as it was estimated in 2012 that
      approximately 70 million adults in the United States are sleeping less than 6 h
      each night, and the average nightly sleep duration of a representative sample of
      the U.S. adult population is reported to be significantly less than in previous
      decades. The underlying mechanisms responsible for chronic sleep loss induced
      insulin resistance include modifications in the regulation of hormone secretion,
      peripheral clock gene regulation, and the cellular signaling processes associated
      with regulating mitochondrial respiratory function. Emerging evidence shows these
      mechanisms share similar biochemical signaling pathways to those underpinning
      exercise-induced adaptations, which together suggest exercise might be a viable,
      suitable, and potent treatment alternative to alleviate sleep loss induced
      insulin resistance and glucose intolerance. In this theoretical review, we
      provide a summary of the impact of reduced sleep duration and quality on
      mitochondrial function and insulin resistance, before detailing the possible
      underlying mechanisms. Finally, we propose how and why regular exercise may be a
      therapeutic intervention to mitigate sleep loss induced mitochondrial dysfunction
      and insulin resistance.

PMID- 29056414
TI  - Effects of sleep changes on pain-related health outcomes in the general
      population: A systematic review of longitudinal studies with exploratory meta
      analysis.
AB  - Emerging longitudinal research has highlighted poor sleep as a risk factor of a
      range of adverse health outcomes, including disabling pain conditions. In
      establishing the causal role of sleep in pain, it remains to be clarified whether
      sleep deterioration over time is a driver of pain and whether sleep improvement
      can mitigate pain-related outcomes. A systematic literature search was performed
      using PubMed MEDLINE, Ovid EMBASE, and Proquest PsycINFO, to identify 16
      longitudinal studies involving 61,000 participants. The studies evaluated the
      effect of sleep changes (simulating sleep deterioration, sleep stability, and
      sleep improvement) on subsequent pain-related outcomes in the general population.
      A decline in sleep quality and sleep quantity was associated with a two- to three
      fold increase in risk of developing a pain condition, small elevations in levels
      of inflammatory markers, and a decline in self-reported physical health status.
      An exploratory meta-analysis further revealed that deterioration in sleep was
      associated with worse self-reported physical functioning (medium effect size),
      whilst improvement in sleep was associated with better physical functioning
      (small effect size). The review consolidates evidence that changes in sleep are
      prospectively associated with pain-related outcomes and highlights the need for
      further longitudinal investigations on the long-term impact of sleep
      improvements.

PMID- 29056416
TI  - The mechanisms of action underlying the efficacy of psychological nightmare
      treatments: A systematic review and thematic analysis of discussed hypotheses.
AB  - Studies of psychotherapeutic treatments for nightmares have yielded support for
      their effectiveness. However, no consensus exists to explain how they work. This
      study combines a systematic review with a qualitative thematic analysis to
      identify and categorize the existing proposed mechanisms of action (MAs) of
      nightmare treatments. The systematic review allowed for a great number of
      scholarly publications on supported psychological treatments for nightmares to be
      identified. Characteristics of the study and citations regarding potential MAs
      were extracted using a standardized coding grid. Then, thematic analysis allowed
      citations to be grouped under six different categories of possible MAs according
      to their similarities and differences. Results reveal that an increased sense of
      mastery was the most often cited hypothesis to explain the efficacy of nightmare
      psychotherapies. Other mechanisms included emotional processing leading to
      modification of the fear structure, modification of beliefs, restoration of sleep
      functions, decreased arousal, and prevention of avoidance. An illustration of the
      different variables involved in the treatment of nightmares is proposed.
      Different avenues for operationalization of these MAs are put forth to enable
      future research on nightmare treatments to measure and link them to efficacy
      measures, and test the implications of the illustration.

PMID- 29056417
TI  - Regulation of glutamate dehydrogenase (GDH) in response to whole body freezing in
      wood frog liver linked to differential acetylation and ADP-ribosylation.
AB  - Glutamate dehydrogenase (GDH) represents a critical enzyme catalyzing the
      reaction spanning amino acid catabolism, the Krebs cycle, and urea production in
      the wood frog. GDH breaks down glutamate and NAD+ to generate alpha-ketoglutaric
      acid (alpha-KG), NADH and ammonium that can be metabolized to form urea.
      Purification of GDH from control and frozen male wood frog livers was performed
      using a two-step column chromatography procedure with a cation exchange column
      and a GTP-agarose affinity column. Analysis of kinetic parameters of the purified
      GDH showed several notable differences between the control and stress. Under
      standard assay conditions, the affinity of GDH for its substrates was
      significantly higher for the freeze-exposed enzyme than for the control
      (glutamate Km: 41% decrease, NAD+ Km: 40% decrease). The maximal activity for the
      control enzyme was also noted to be lower than the frozen. This suggests that the
      frozen form of the GDH was activated relative to the control form. Western blot
      analysis of common posttranslational modifications indicated that the frozen
      enzyme had a lower degree of acetylation and ADP-ribosylation than its control
      counterpart. These results suggest that GDH is regulated in the wood frog liver
      by means of altering post-translational modifications in response to freezing.

PMID- 29056418
TI  - Hemodynamic effects of dexmedetomidine, with and without MK-467, following
      intramuscular administration in cats anesthetized with isoflurane.
AB  - OBJECTIVE: To characterize the hemodynamic effects of dexmedetomidine, with or
      without MK-467, following intramuscular (IM) administration in cats. STUDY
      DESIGN: Randomized, crossover, experimental study. ANIMALS: Six healthy adult
      male castrated purpose-bred cats. METHODS: Cats were anesthetized with isoflurane
      in oxygen and instrumented. Cats were administered dexmedetomidine (25 MUg kg-1),
      with (DM) or without (D) MK-467 (600 MUg kg-1), IM in the epaxial muscles.
      Cardiovascular variables, respiratory variables, temperature, and arterial and
      mixed-venous pH, blood gases and electrolytes were measured prior to drug
      administration and at various time points for 6 hours thereafter, during
      anesthesia with isoflurane. Additional variables were calculated from the
      measurements, using standard equations. Results were analyzed with a two-way
      repeated-measures analysis of variance, followed by Dunnett's and paired t tests
      where appropriate. RESULTS: Dexmedetomidine resulted in a significant decrease in
      cardiac index (CI) and significant increases in mean arterial pressure (MAP) and
      systemic vascular resistance index (SVRI). The addition of MK-467 failed to
      prevent most of the early cardiovascular effects of dexmedetomidine, but the
      duration of systemic vasoconstriction was shorter and CI did not decrease. The
      lowest and highest post-treatment values in each treatment were 0.1 +/- 0.03 and
      0.13 +/- 0.03 L minute-1 BW-0.67 (D) versus 0.14 +/- 0.01 and 0.19 +/- 0.03 L
      minute-1 BW-0.67 (DM) for CI, 87 +/- 13 and 181 +/- 21 mmHg (D) versus 70 +/- 11
      and 153 +/- 18 mmHg (DM) for MAP and 58,948 +/- 17,754 and 119,432 +/- 40,423
      dynes second cm-5 BW-0.67 (D) versus 25,870 +/- 3782 and 76,498 +/- 17,258 dynes
      second cm-5 BW-0.67 (DM) for SVRI, respectively. CONCLUSION AND CLINICAL
      RELEVANCE: IM coadministration of MK-467 and dexmedetomidine in isoflurane
      anesthetized cats shortened dexmedetomidine-induced cardiovascular effects. This
      drug combination may be useful in cats in which longer-lasting hypertension and
      hemodynamic depression is of concern.

PMID- 29056419
TI  - Fungal Cordycepin Biosynthesis Is Coupled with the Production of the Safeguard
      Molecule Pentostatin.
AB  - Cordycepin (COR) and pentostatin (PTN) are adenosine analogs with related
      bioactivity profiles as both mimic adenosine and can inhibit some of the
      processes that are adenosine dependent. Both COR and PTN are also natural
      products and were originally isolated from the fungus Cordyceps militaris and the
      bacterium Streptomyces antibioticus, respectively. Here, we report that not only
      is PTN produced by C. militaris but that biosynthesis of COR is coupled with PTN
      production by a single gene cluster. We also demonstrate that this coupling is an
      important point of metabolic regulation where PTN safeguards COR from deamination
      by inhibiting adenosine deaminase (ADA) activity. ADA is not inhibited until COR
      reaches self-toxic levels, at which point ADA derepression occurs allowing for
      detoxification of COR to 3'-deoxyinosine. Finally, we show that using our
      biosynthetic insights, we can engineer C. militaris to produce higher levels of
      COR and PTN.

PMID- 29056420
TI  - USP7-Specific Inhibitors Target and Modify the Enzyme's Active Site via Distinct
      Chemical Mechanisms.
AB  - USP7 is a deubiquitinating enzyme that plays a pivotal role in multiple oncogenic
      pathways and therefore is a desirable target for new anti-cancer therapies.
      However, the lack of structural information about the USP7-inhibitor interactions
      has been a critical gap in the development of potent inhibitors. USP7 is unique
      among USPs in that its active site is catalytically incompetent, and is
      postulated to rearrange into a productive conformation only upon binding to
      ubiquitin. Surprisingly, we found that ubiquitin alone does not induce an active
      conformation in solution. Using a combination of nuclear magnetic resonance, mass
      spectrometry, computational modeling, and cell-based assays, we found that DUB
      inhibitors P22077 and P50429 covalently modify the catalytic cysteine of USP7 and
      induce a conformational switch in the enzyme associated with active site
      rearrangement. This work represents the first experimental insights into USP7
      activation and inhibition and provides a structural basis for rational
      development of potent anti-cancer therapeutics.

PMID- 29056421
TI  - Structure-Guided Development of a Potent and Selective Non-covalent Active-Site
      Inhibitor of USP7.
AB  - Deubiquitinating enzymes (DUBs) have garnered significant attention as drug
      targets in the last 5-10 years. The excitement stems in large part from the
      powerful ability of DUB inhibitors to promote degradation of oncogenic proteins,
      especially proteins that are challenging to directly target but which are
      stabilized by DUB family members. Highly optimized and well-characterized DUB
      inhibitors have thus become highly sought after tools. Most reported DUB
      inhibitors, however, are polypharmacological agents possessing weak (micromolar)
      potency toward their primary target, limiting their utility in target validation
      and mechanism studies. Due to a lack of high-resolution DUB?small-molecule ligand
      complex structures, no structure-guided optimization efforts have been reported
      for a mammalian DUB. Here, we report a small-molecule?ubiquitin-specific protease
      (USP) family DUB co-structure and rapid design of potent and selective inhibitors
      of USP7 guided by the structure. Interestingly, the compounds are non-covalent
      active-site inhibitors.

PMID- 29056422
TI  - The effect of antipyretics on immune response and fever following receipt of
      inactivated influenza vaccine in young children.
AB  - BACKGROUND: Antipyretics reduce fever following childhood vaccinations; after
      inactivated influenza vaccine (IIV) they might ameliorate fever and thereby
      decrease febrile seizure risk, but also possibly blunt the immune response. We
      assessed the effect of antipyretics on immune responses and fever following IIV
      in children ages 6 through 47 months. METHODS: Over the course of three seasons,
      one hundred forty-two children, receiving either a single or the first of 2
      recommended doses of IIV, were randomized to receive either oral acetaminophen
      suspension (n = 59) or placebo (n = 59) (double-blinded) or ibuprofen (n = 24)
      (open-label) immediately following IIV and every 4-8 h thereafter for 24 h. Blood
      samples were obtained at enrollment and 4 weeks following the last recommended
      IIV dose. Responses to IIV were assessed by hemagglutination inhibition assay
      (HAI). Seroprotection was defined as an HAI titer >=1:40 and seroconversion as a
      titer >=1:40 if baseline titer <1:10 or four-fold rise if baseline titer >=1:10.
      Participants were monitored for fever and other solicited symptoms on the day of
      and day following IIV. RESULTS: Significant differences in seroconversion and
      post-vaccination seroprotection were not observed between children included in
      the different antipyretic groups and the placebo group for the vaccine antigens
      included in IIV over the course of the studies. Frequencies of solicited
      symptoms, including fever, were similar between treatment groups and the placebo
      group. CONCLUSIONS: Significant blunting of the immune response was not observed
      when antipyretics were administered to young children receiving IIV. Studies with
      larger sample sizes are needed to definitively establish the effect of
      antipyretics on IIV immunogenicity.

PMID- 29056423
TI  - Effect of recombinant glutathione S-transferase as vaccine antigen against
      Rhipicephalus appendiculatus and Rhipicephalus sanguineus infestation.
AB  - The ticks Rhipicephalus appendiculatus and Rhipicephalus sanguineus are the main
      vectors of Theileria parva and Babesia spp. in cattle and dogs, respectively. Due
      to their impact in veterinary care and industry, improved methods against R.
      appendiculatus and R. sanguineus parasitism are under development, including
      vaccines. We have previously demonstrated the induction of a cross-protective
      humoral response against Rhipicephalus microplus following vaccination with
      recombinant glutathione S-transferase from Haemaphysalis longicornis tick (rGST
      Hl), suggesting that this protein could control tick infestations. In the present
      work, we investigated the effect of rGST-Hl vaccine against R. appendiculatus and
      R. sanguineus infestation in rabbits. In silico analysis revealed that GST from
      H. longicornis, R. appendiculatus and R. sanguineus have >80% protein sequence
      similarity, and multiple conserved antigenic sites. After the second vaccine
      dose, rGST-Hl-immunized rabbits showed elevated antibody levels which persisted
      until the end of experiment (75 and 60 days for R. appendiculatus and R.
      sanguineus, respectively). Western blot assays demonstrated cross-reactivity
      between anti-rGST-Hl antibodies and native R. appendiculatus and R. sanguineus
      GST extracts from ticks at different life stages. Vaccination with rGST-Hl
      decreased the number, weight, and fertility of engorged R. appendiculatus adults,
      leading to an overall vaccine efficacy of 67%. Interestingly, histological
      analysis of organ morphology showed damage to salivary glands and ovaries of R.
      appendiculatus adult females fed on vaccinated animals. In contrast, rGST-Hl
      vaccination did not affect R. appendiculatus nymphs, and it was ineffective
      against R. sanguineus across the stages of nymph and adult. Taken together, our
      results show the potential application of rGST-Hl as an antigen in anti-tick
      vaccine development, however indicating a broad difference in efficacy among tick
      species.

PMID- 29056424
TI  - Implementing near real-time vaccine safety surveillance using the Clinical
      Practice Research Datalink (CPRD).
AB  - INTRODUCTION: Near real-time vaccine safety surveillance (NRTVSS) using
      electronic health records is increasingly used to rapidly detect vaccine safety
      signals. NRTVSS has not been fully implemented in the UK. We assessed the
      feasibility of implementing this surveillance using the UK Clinical Practice
      Research Datalink (CPRD). METHODS: We selected seasonal influenza
      vaccine/Guillain-Barre Syndrome (GBS) as an example of a rare outcome and measles
      mumps-rubella (MMR) vaccine/febrile seizures as a positive control. For
      influenza/GBS we implemented a system for the 2013/2014 and 2014/2015 influenza
      seasons; for MMR/seizures the surveillance period was July 2014-June 2015. We
      used the continuous Poisson-based maximized sequential probability ratio test
      (PMaxSPRT), comparing observed-to-expected events, for both pairs. We calculated
      an age-sex-adjusted rate using 5years of historic data and used this rate to
      calculate the expected number of events in pre-specified post-vaccination risk
      window (GBS: 0-42days, seizures: 6-21days). For MMR/seizures we also implemented
      the system using the Binominal-based maximized sequential probability ratio test
      (BMaxSPRT). For this, we compared seizures in the risk-window (6-21days) to a
      control window (0-5 and 22-32days). Delays in recording outcomes influence the
      data available, so we adjusted the expected number of events using a historical
      distribution of delays in recording GBS/febrile seizures. Analyses were run using
      data up to each CPRD monthly release. We also performed power calculations for
      detecting increases in relative risk (RR) from 1.5 to 10. RESULTS: For
      influenza/GBS we implemented a system in both seasons with no signal. Power to
      detect a signal was >80% for RR>=4. For MMR/seizures we were able to identify a
      signal with PMaxSPRT but not with BMaxSPRT. Power>=80% for RR>=2.5 for both
      tests. CONCLUSION: CPRD is a potential data source to implement NRTVSS to exclude
      large increases in the risk of rare outcomes after seasonal influenza and lower
      increases in risk for more frequent outcomes.

PMID- 29056425
TI  - Ethics, pregnancy, and ZIKV vaccine research & development.

PMID- 29056427
TI  - Consequences of continuous social defeat stress on anxiety- and depressive-like
      behaviors and ethanol reward in mice.
AB  - This study employed the intruder-resident paradigm to evaluate the effects of
      continuous social defeat on depressive- and anxiety-like behaviors and the
      reinforcing and motivational actions of ethanol in male Swiss mice. Male Swiss
      mice were exposed to a 10-day social defeat protocol, while control mice
      cohabitated with a non-aggressive animal. Continuous defeat stress consisted of
      episodes of defeat, followed by 24h or 48h cohabitation with the aggressor until
      the following defeat. Mice were assessed for sucrose drinking (anhedonia), social
      investigation test, elevated plus-maze, conditioned place preference to ethanol,
      and locomotor response to ethanol. Plasma corticosterone was measured prior to,
      after the first and the final defeat, and 10days after the end of defeat.
      Defeated mice exhibited a depressive-like phenotype as indicated by social
      inhibition and reduced sucrose preference, relative to non-defeated controls.
      Defeated mice also displayed anxiety-like behavior when tested in the elevated
      plus-maze. Stressed animals failed to present ethanol-induced locomotor
      stimulation, but showed increased sensitivity for ethanol-induced conditioned
      place preference. Corticosterone response to defeat was the highest after the
      first defeat, but was still elevated after the last defeat (day 10) when compared
      to non-stressed controls. Baseline corticosterone levels were unchanged 10days
      after the final defeat. These data suggest that social defeat stress increased
      depressive- and anxiety-like behavior as well increased vulnerability to ethanol
      reward in mice.

PMID- 29056426
TI  - mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a
      Targetable Metabolic Vulnerability.
AB  - The mechanistic target of rapamycin complex 1 (mTORC1) supports proliferation
      through parallel induction of key anabolic processes, including protein, lipid,
      and nucleotide synthesis. We hypothesized that these processes are coupled to
      maintain anabolic balance in cells with mTORC1 activation, a common event in
      human cancers. Loss of the tuberous sclerosis complex (TSC) tumor suppressors
      results in activation of mTORC1 and development of the tumor syndrome TSC. We
      find that pharmacological inhibitors of guanylate nucleotide synthesis have
      selective deleterious effects on TSC-deficient cells, including in mouse tumor
      models. This effect stems from replication stress and DNA damage caused by mTORC1
      driven rRNA synthesis, which renders nucleotide pools limiting. These findings
      reveal a metabolic vulnerability downstream of mTORC1 triggered by anabolic
      imbalance.

PMID- 29056428
TI  - A Lipoylated Metabolic Protein Released by Staphylococcus aureus Suppresses
      Macrophage Activation.
AB  - The virulence factors of pathogenic microbes often have single functions that
      permit immune suppression. However, a proportion possess multiple activities and
      are considered moonlighting proteins. By examining secreted virulence factors of
      Staphylococcus aureus, we determine that the bacterial lipoic acid synthetase
      LipA suppresses macrophage activation. LipA is known to modify the E2 subunit of
      the metabolic enzyme complex pyruvate dehydrogenase (E2-PDH) with a fatty acid
      derivative, lipoic acid, yielding the metabolic protein lipoyl-E2-PDH. We
      demonstrate that lipoyl-E2-PDH is also released by S. aureus and moonlights as a
      macrophage immunosuppressant by reducing Toll-like receptor 1/2 (TLR1/2)
      activation by bacterial lipopeptides. A LipA-deficient strain induces heightened
      pro-inflammatory cytokine production, which is diminished in the absence of TLR2.
      During murine systemic infection, LipA suppresses pro-inflammatory macrophage
      activation, rendering these cells inefficient at controlling infection. These
      observations suggest that bacterial metabolism and immune evasion are linked by
      virtue of this moonlighting protein.

PMID- 29056429
TI  - Three-Dimensional Microbiome and Metabolome Cartography of a Diseased Human Lung.
AB  - Our understanding of the spatial variation in the chemical and microbial makeup
      of an entire human organ remains limited, in part due to the size and
      heterogeneity of human organs and the complexity of the associated metabolome and
      microbiome. To address this challenge, we developed a workflow to enable the
      cartography of metabolomic and microbiome data onto a three-dimensional (3D)
      organ reconstruction built off radiological images. This enabled the direct
      visualization of the microbial and chemical makeup of a human lung from a cystic
      fibrosis patient. We detected host-derived molecules, microbial metabolites,
      medications, and region-specific metabolism of medications and placed it in the
      context of microbial distributions in the lung. Our tool further created
      browsable maps of a 3D microbiome/metabolome reconstruction map on a radiological
      image of a human lung and forms an interactive resource for the scientific
      community.

PMID- 29056431
TI  - Effects of surgical lesions on choline acetyltransferase activity in the cat
      cochlea.
AB  - Although it is well established that the choline acetyltransferase (ChAT, the
      enzyme for acetylcholine synthesis) in the mammalian cochlea is associated with
      its olivocochlear innervation, the distribution of this innervation in the
      cochlea varies somewhat among mammalian species. The quantitative distribution of
      ChAT activity in the cochlea has been reported for guinea pigs and rats. The
      present study reports the distribution of ChAT activity within the organ of Corti
      among the three turns of the cat cochlea and the effects of removing
      olivocochlear innervation either by a lateral cut aimed to totally transect the
      left olivocochlear bundle or a more medial cut additionally damaging the superior
      olivary complex on the same side. Similarly to results for guinea pig and rat,
      the distribution of ChAT activity in the cat outer hair cell region showed a
      decrease from base to apex, but, unlike in the guinea pig and rat, the cat inner
      hair cell region did not. As in the rat, little ChAT activity was measured in the
      outer supporting cell region. As previously reported for whole cat cochlea and
      for rat cochlear regions, transection of the olivocochlear bundle resulted in
      almost total loss of ChAT activity in the hair cell regions of the cat cochlea.
      Lesions of the superior olivary complex resulted in loss of ChAT activity in the
      inner hair cell region of all cochlear turns only on the lesion side but
      bilateral losses in the outer hair cell region of all turns. The results are
      consistent with previous evidence that virtually all cholinergic synapses in the
      mammalian cochlea are associated with its olivocochlear innervation, that the
      olivocochlear innervation to the inner hair cell region is predominantly
      ipsilateral, and that the olivocochlear innervation to the outer hair cells is
      bilateral.

PMID- 29056432
TI  - Tinnitus with a normal audiogram: Role of high-frequency sensitivity and
      reanalysis of brainstem-response measures to avoid audiometric over-matching.

PMID- 29056430
TI  - A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in
      Some Ferrets Infected via Respiratory Droplets.
AB  - Low pathogenic H7N9 influenza viruses have recently evolved to become highly
      pathogenic, raising concerns of a pandemic, particularly if these viruses acquire
      efficient human-to-human transmissibility. We compared a low pathogenic H7N9
      virus with a highly pathogenic isolate, and two of its variants that represent
      neuraminidase inhibitor-sensitive and -resistant subpopulations detected within
      the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice,
      ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets
      than the low pathogenic H7N9 virus, with the exception of the neuraminidase
      inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses
      transmitted among ferrets via respiratory droplets, and the neuraminidase
      sensitive variant killed several of the infected and exposed animals.
      Neuraminidase inhibitors showed limited effectiveness against these viruses in
      vivo, but the viruses were susceptible to a polymerase inhibitor. These results
      suggest that the highly pathogenic H7N9 virus has pandemic potential and should
      be closely monitored.

PMID- 29056433
TI  - Perceptions of the Harm and Addictiveness of Conventional Cigarette Smoking Among
      Adolescent E-Cigarette Users.
AB  - PURPOSE: Although existing evidence indicates that e-cigarette use is a risk
      factor for cigarette smoking initiation, mechanisms of this association are not
      yet known. E-cigarette users perceive e-cigarette use to be less harmful relative
      to conventional cigarettes, but their absolute perceptions of addictiveness of
      conventional cigarette smoking are unknown. This study examines how e-cigarette
      users compare with nonusers (non-e-cigarette users/nonconventional cigarette
      smokers), conventional cigarette smokers, and dual users on perceptions of harm
      and the addictiveness of conventional cigarette smoking and on other known
      predictors of cigarette smoking such as peer smoking, influence of antismoking
      ads, and risk-taking propensity. METHODS: National samples of 8th- and 10th-grade
      students from 2014 and 2015 (N = 14,151) were obtained from the Monitoring the
      Future Study. Multivariate logistic regression models were used to examine
      relationships between adolescent smoking status and perceptions of harm and the
      addictiveness of conventional cigarette smoking while controlling for potential
      confounders. RESULTS: E-cigarette users had lower perceptions of the
      addictiveness of conventional cigarette smoking compared with nonusers but higher
      than cigarette smokers and dual users. E-cigarette users reported lower influence
      by antismoking ads, more conventional cigarette-smoking peers, and greater risk
      taking propensity than nonusers. E-cigarette users and cigarette smokers did not
      differ in their perceived harm of conventional cigarette smoking or in their risk
      taking propensity. CONCLUSIONS: E-cigarette users' attitudes and perceptions
      regarding conventional cigarette smoking may leave them vulnerable to becoming
      conventional cigarette smokers. Future studies should explore the prospective
      relationship between smoking-related perceptions of conventional cigarette
      smoking among e-cigarette users and the onset of cigarette smoking.

PMID- 29056434
TI  - Dim Light Melatonin Onset and Affect in Adolescents With an Evening Circadian
      Preference.
AB  - PURPOSE: A shift toward an evening circadian preference and the onset of mood
      problems often occur during adolescence. Although these changes are linked to
      poorer outcomes, few studies have considered how positive and negative affect are
      related to the circadian rhythm during adolescence. This study examined the
      relationship between evening and morning affect ratings and dim light melatonin
      onset (DLMO), a measure of endogenous circadian rhythm. Age and sex were tested
      as moderators. METHODS: This study is based on a subset of 163 (94 female, age =
      14.7) adolescents with an evening circadian preference from a National Institute
      of Child Health and Human Development-funded study. Participants provided saliva
      for melatonin analysis and rated evening and morning affect. RESULTS: Higher
      evening negative affect was related to a later DLMO. Evening positive affect was
      not significantly related to DLMO timing. Age but not sex was a significant
      moderator such that higher negative and lower positive affect were related to a
      later DLMO for 10- to 13-year-olds, whereas higher positive affect was related to
      a later DLMO for 17- to 18-year-olds. DLMO was not significantly related to
      morning affect ratings. CONCLUSIONS: There is evidence that higher negative and
      lower positive affect may be related to the shift toward an evening circadian
      preference observed in adolescents, particularly for younger adolescents.

PMID- 29056435
TI  - Experiences of Vaginal, Oral, and Anal Sex From Adolescence to Early Adulthood in
      Populations With Physical Disabilities.
AB  - PURPOSE: Few studies have sought to understand the typical sexual development of
      populations with physical disabilities in the United States, and those that do
      are often based on convenience samples or cross-sectional data. The purpose of
      this paper is to examine relationships between physical disability and
      experiences of vaginal, oral, and anal sex in a nationally representative sample
      of individuals in the United States who have been followed from adolescence
      through early adulthood. METHODS: We used data from 13,456 respondents who
      completed Waves I (1994-1995) and IV (2008-2009) of the National Longitudinal
      Study of Adolescent to Adult Health (Add Health). Physical disabilities were
      identified and grouped by severity using information regarding limb difficulties,
      blindness, and deafness during adolescence. Analyses included bivariate
      statistics and adjusted logistic regression models relating physical disability
      and experiences of each type of sex. RESULTS: Respondents with the most severe
      physical disabilities had significantly lower odds of experiencing vaginal sex,
      oral sex, and having any sexual experience compared with the odds of those
      without disabilities. After stratifying by biological sex, we found that males
      with the most severe physical disabilities had significantly lower odds of
      experiencing any type of sex compared with the odds of males without
      disabilities, whereas females with moderate and severe physical disabilities had
      significantly lower odds of experiencing vaginal sex compared with the odds of
      females without disabilities. CONCLUSIONS: Our findings build on past research
      often conducted with convenience samples or cross-sectional data, indicating
      variation in sexual experiences among populations with disabilities.

PMID- 29056436
TI  - Physiologic Response to Gender-Affirming Hormones Among Transgender Youth.
AB  - PURPOSE: The purpose of this study was to examine the physiologic impact of
      hormones on youth with gender dysphoria. These data represent follow-up data in
      youth ages 12-23 years over a two-year time period of hormone administration.
      METHODS: This prospective, longitudinal study initially enrolled 101 youth with
      gender dysphoria at baseline from those presenting consecutively for care between
      February 2011 and June 2013. Physiologic data at baseline and follow-up were
      abstracted from medical charts. Data were analyzed by descriptive statistics.
      RESULTS: Of the initial 101 participants, 59 youth had follow-up physiologic data
      collected between 21 and 31 months after initiation of hormones available for
      analysis. Metabolic parameters changes were not clinically significant, with the
      exception of sex steroid levels, intended to be the target of intervention.
      CONCLUSIONS: Although the impact of hormones on some historically concerning
      physiologic parameters, including lipids, potassium, hemoglobin, and prolactin,
      were statistically significant, clinical significance was not observed. Hormone
      levels physiologically concordant with gender of identity were achieved with
      feminizing and masculinizing medication regimens. Extensive and frequent
      laboratory examination in transgender adolescents may be unnecessary. The use of
      hormones in transgender youth appears to be safe over a treatment course of
      approximately two years.

PMID- 29056437
TI  - Texting to Increase Contraceptive Initiation Among Adolescents in the Emergency
      Department.
AB  - PURPOSE: To evaluate the feasibility and acceptability of a text messaging
      intervention to increase contraception among adolescent emergency department
      patients. METHODS: A pilot randomized controlled trial of sexually active females
      aged 14-19 receiving 3 months of theory-based, unidirectional educational and
      motivational texts providing reproductive health information versus standardized
      discharge instructions. Blinded assessors measured contraception initiation via
      telephone follow-up and health record review at 3 months. RESULTS: We randomized
      100 eligible participants (predominantly aged 18-19, Hispanic, and with a primary
      provider); 88.0% had follow-up. In the intervention arm, 3/50 (6.0%) participants
      opted out, and 1,172/1,654 (70.9%) texts were successfully delivered; over 90% of
      message failures were from one mobile carrier. Most (36/41; 87.7%) in the
      intervention group liked and wanted future reproductive health messages.
      Contraception was initiated in 6/50 (12.0%) in the intervention arm and in 11/49
      (22.4%) in the control arm. CONCLUSIONS: A pregnancy prevention texting
      intervention was feasible and acceptable among adolescent females in the
      emergency department setting.

PMID- 29056438
TI  - The Association of Intergenerational Mismatch With Adiposity and Blood Pressure
      in Childhood and Adolescence.
AB  - PURPOSE: An intergenerational "mismatch," a transition from limited to plentiful
      living conditions over generations, may increase cardiovascular disease risks. In
      a migrant population within a homogenous culture, we tested the hypothesis that
      an intergenerational mismatch in childhood living condition is associated with
      higher body mass index (BMI) and blood pressure in childhood and adolescence.
      METHODS: We used data from 6,965 native born Chinese in Hong Kong (participated
      in "Children of 1997" birth cohort) and migrant Chinese born elsewhere in China
      in 1997 (N = 9,845). We classified children into those with intergenerational
      mismatch (child migrants or first-generation migrants) or those without (second+
      generation migrants). Generalized estimating equations were used to examine the
      associations of migration status (child migrants, first-generation migrants or
      second+-generation migrants) with age- and sex-specific BMI z-score at 8-15 years
      and age-, sex-, and height-specific blood pressure z-score at 11-13 years,
      adjusted for sex, month of birth, and age. RESULTS: Compared with second+
      generation migrants, first-generation migrants had higher diastolic blood
      pressure z-score (.04, 95% confidence interval (CI) .02, .06) and BMI z-score
      (.12, 95% CI .06, .18), whereas child migrants had higher diastolic blood
      pressure z-score (.03, 95% CI .01, .05) regardless of age at migration and higher
      BMI z-score if they had migrated in infancy (.17, 95% CI .11, .23). CONCLUSION:
      Different relations for blood pressure and BMI suggest that intergenerational
      mismatch and proximal exposures may have different impacts on adiposity and blood
      pressure.

PMID- 29056439
TI  - New Molecular Mechanisms to Reduce Arsenic in Crops.
AB  - Arsenic is toxic to all life forms and is a potent carcinogen. Its accumulation
      in crop plants and subsequent consumption poses a serious threat to public health
      worldwide. Recent developments have enhanced our understanding of the molecular
      mechanisms governing arsenic uptake, detoxification, and accumulation in plants.
      In particular, the identification of plant arsenate reductase enzymes and
      emerging details of the processes underlying arsenic distribution and deposition
      in the seed will prove invaluable in the development of new strategies to
      mitigate this threat. Here we provide an outline of these recent developments and
      suggest new molecular mechanisms that could be employed to reduce arsenic in
      crops.

PMID- 29056440
TI  - Making Roots, Shoots, and Seeds: IDD Gene Family Diversification in Plants.
AB  - The INDETERMINATE DOMAIN (IDD) family of transcriptional regulators controls a
      diversity of processes in a variety of plant tissues and organs and at different
      stages of plant development. Several recent reports describe the genetic
      characterization of IDD family members, including those that are likely to
      regulate C4 kranz anatomy, with implications for the engineering of C4 traits
      into C3 crops. In this review we summarize the reported functions of IDD members
      in the regulation of metabolic sensing and leaf, root, seed, and inflorescence
      development. We also provide an IDD phylogeny for the grasses and suggest future
      directions and strategies to define the function of IDDs in C4 photosynthesis and
      other developmental processes.

PMID- 29056441
TI  - Use of a novel sentinel lymph node mapping algorithm reduces the need for pelvic
      lymphadenectomy in low-grade endometrial cancer.
AB  - OBJECTIVES: To evaluate the capability of a novel sentinel lymph node (SLN)
      mapping algorithm to reduce the need for pelvic lymphadenectomy (PLND) in
      patients with low-grade (G1-2) endometrial cancer (LGEC). METHODS: Patients with
      LGEC underwent evaluation according to a novel lymphatic assessment algorithm
      during hysterectomy with SLN biopsy at two academic gynecologic oncology
      programs. Side-specific PLND was only performed if ipsilateral SLN mapping failed
      and high-risk uterine features were identified on frozen section (FS). Side
      specific and PLND rates were compared to theoretical PLND rates based on the NCCN
      EC SLN mapping algorithm. RESULTS: Since 11/2015, 113 LGEC patients have been
      managed according to the algorithm. SLN mapping was bilateral (81%), unilateral
      (12%), or neither (6%). Nine patients (8.0%) had LN metastases identified. Of the
      21 patients requiring intraoperative FS due to failed SLN mapping, high-risk
      uterine features were identified in eight (38%). These patients underwent either
      bilateral (2) or unilateral (6) PLND. Side-specific and overall PLND rates were
      5.3% and 7.1%, respectively. If all patients with failed mapping had undergone
      PLND according to the NCCN algorithm, side-specific and overall PLND rates would
      have been higher, 12.4% and 18.6%, respectively (P=0.01). All patients who failed
      to map and did not undergo side-specific PLND had low-risk uterine features on
      final pathology. CONCLUSIONS: Lymphatic assessment using SLN mapping followed by
      selective FS to determine need for PLND is feasible. When compared to the NCCN
      algorithm, this novel "Reflex Frozen Section" strategy eliminates PLND in
      patients at lowest risk for metastasis without compromising identification of
      metastatic nodal disease.

PMID- 29056443
TI  - Pre-clinical evaluation of a themosensitive gel containing epothilone B and
      mTOR/Hsp90 targeted agents in an ovarian tumor model.
AB  - Despite clinical remission of epithelial ovarian cancer (EOC) after surgical
      resection and first-line chemotherapy, about 60% of patients will re-develop
      peritoneal metastasis and about 50% will relapse with chemoresistant disease.
      Clinical studies suggest that intra-peritoneal (i.p.) chemotherapy effectively
      treats residual EOC after cyto-reduction by gaining direct access into the
      peritoneal cavity, enabling elevated drug levels versus intravenous (i.v.)
      injection. However, chemoresistant disease is still problematic. To overcome
      resistance against microtubule stabilizing agents such as taxanes, epothilone B
      (EpoB) has merit, especially in combination with molecular targeted agents that
      inhibit heat shock protein 90 (Hsp90) and/or mammalian target of rapamycin
      (mTOR). In this paper, we report on the successful loading and solubilization of
      EpoB in a poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block
      poly(d,l-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) thermosensitive gel (g-E).
      Further, we report on successful co-loading of 17-AAG (Hsp90) and rapamycin
      (mTOR) (g-EAR). After i.p. injection in mice, g-EAR showed gelation in the
      peritoneum and sustained, local-regional release of EpoB, 17-AAG, and rapamycin.
      In a luciferase-expressing ES-2 (ES-2-luc) ovarian cancer xenograft model, single
      i.p. injections of g-E and g-EAR delayed bioluminescence from metastasizing ES-2
      luc cells for 2 and 3weeks, respectively, despite fast drug release for g-EAR in
      vivo versus in vitro. In summary, a PLGA-b-PEG-b-PLGA sol-gel has loading and
      release capacities for EpoB and its combinations with 17-AAG and rapamycin,
      enabling a platform for i.p. delivery, sustained multi-drug exposure, and potent
      antitumor efficacy in an ES-2-luc, ovarian cancer i.p. xenograft model.

PMID- 29056442
TI  - Salvage chemotherapy with taxane and platinum for women with recurrent uterine
      carcinosarcoma.
AB  - OBJECTIVE: To examine survival after recurrence (SAR) among women with recurrent
      uterine carcinosarcoma who received a taxane/platinum doublet as the first-line
      salvage chemotherapy. METHODS: We retrospectively examined 148 women with
      recurrent uterine carcinosarcoma who received salvage chemotherapy within a
      cohort of 906 uterine carcinosarcomas. An independent association of salvage
      chemotherapy type and SAR was examined with multivariate analysis. RESULTS: There
      were 71 (48.0%) women who received a taxane/platinum regimen. On univariate
      analysis, women who received a taxane/platinum doublet had a higher 2-year SAR
      rate compared to women who received non-taxane/platinum regimens (55.5% versus
      34.8%, P<0.001). On multivariate analysis, use of taxane/platinum regimen was
      independently associated with improved SAR compared to the non-taxane/platinum
      regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to
      0.91, P=0.02). When stratified by disease-free interval, women with a disease
      free interval >=6months who received a taxane/platinum doublet had a higher 2
      year SAR rate compared to those who received non-taxane/platinum regimens (61.9%
      versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P=0.002); conversely, in women with a
      disease-free interval <6months, 2-year SAR rates were similar between the two
      groups (20.5% versus 18.4%, HR 0.80, 95% CI 0.33 to 1.90, P=0.61). Among women
      who received a taxane/platinum doublet as adjuvant chemotherapy, re-treatment
      with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year
      SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P=0.019). CONCLUSION:
      Our study suggests that taxane/platinum doublet may be a more effective
      chemotherapy regimen compared to other regimens among women with recurrent
      uterine carcinosarcoma, especially for those who had a disease-free interval of
      >=6months.

PMID- 29056445
TI  - Characteristics of cerebral hemodynamics assessed by CT perfusion in moyamoya
      disease.
AB  - Due to the recent development of multidetector row computed tomography (CT),
      hemodynamic parameters can now be conveniently obtained with CT perfusion. The
      purpose of this study is to characterize the hemodynamic parameters of CT
      perfusion in moyamoya disease, and to discuss the differences in collateral
      circulation between moyamoya disease and atherosclerotic disease. A total of 16
      hemispheric sides of 15 patients with moyamoya disease and 10 hemispheric sides
      of 9 patients with atherosclerotic disease who underwent bypass surgery were
      included. CT perfusion was performed with 123I-IMP SPECT. Cerebral blood flow
      (CBF), cerebral blood volume (CBV), and mean transit time (MTT) values obtained
      by CT perfusion using standard singular value decomposition as the deconvolution
      algorithm in moyamoya disease were calculated. Preoperative values of these
      parameters were compared with those of atherosclerotic disease. Then, the
      postoperative changes of these parameters were analyzed. In the impaired side,
      CBF as measured by CT perfusion was correlated with that measured by 123I-IMP
      SPECT. In moyamoya disease, CBV as measured by CT perfusion was significantly
      increased compared to in atherosclerotic disease, yet CBF was significantly
      decreased in atherosclerotic disease. Postoperatively, the asymmetry ratios of
      MTT were significantly improved, especially in atherosclerotic disease compared
      with moyamoya disease. On CT perfusion, the parameters included transit time and
      arrival time. CBV increase in moyamoya disease and postoperative improvement of
      MTT, especially in atherosclerotic disease, were unique characteristics in each.
      This might be due to the difference of collateral circulation and compensatory
      mechanisms between moyamoya disease and atherosclerotic disease.

PMID- 29056444
TI  - Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by
      skin immunization with live virus vectored microneedle arrays.
AB  - The generation of tissue resident memory (TRM) cells at the body surfaces to
      provide a front line defence against invading pathogens represents an important
      goal in vaccine development for a wide variety of pathogens. It has been widely
      assumed that local vaccine delivery to the mucosae is necessary to achieve that
      aim. Here we characterise a novel micro-needle array (MA) delivery system
      fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector
      (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the
      microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the
      generation of long-lived antigen-specific CD8+ T cells that accumulate in mucosal
      tissues, including the female genital and respiratory tract. The memory CD8+ T
      cell population maintained in the peripheral mucosal tissues was attributable to
      a MA delivered AdHu5 vaccine instructing CD8+ T cell expression of CXCR3+,
      CD103+, CD49a+, CD69+, CD127+ homing, retention and survival markers.
      Furthermore, memory CD8+ T cells generated by MA immunization significantly
      expanded upon locally administered antigenic challenge and showed a predominant
      poly-functional profile producing high levels of IFNgamma and Granzyme B. These
      data demonstrate that skin vaccine delivery using microneedle technology induces
      mobilization of long lived, poly-functional CD8+ T cells to peripheral tissues,
      phenotypically displaying hallmarks of residency and yields new insights into how
      to design and deliver effective vaccine candidates with properties to exert local
      immunosurveillance at the mucosal surfaces.

PMID- 29056446
TI  - Evaluation of the rapid biochemical beta-CARBATM test for detection of
      carbapenemase-producing Gram-negative bacteria.
AB  - We evaluated a rapid biochemical screening test beta-CARBATM for detection of
      Gram-negative carbapenemase producers. The sensitivity of the test after 30min
      incubation was 98.2%, but increased to 100% after 1h. beta-CARBATM proved
      reliable for carbapenemase screening in Acinetobacter spp. for which currently no
      commercial phenotypic assays are available.

PMID- 29056447
TI  - Comparison of ten different DNA extraction procedures with respect to their
      suitability for environmental samples.
AB  - DNA extraction for molecular biological applications usually requires target
      optimized extraction procedures depending on the origin of the samples. For
      environmental samples, a range of different procedures has been developed. We
      compared the applicability and efficiency of ten selected DNA extraction methods
      published in recent literature using four different environmental samples namely:
      activated sludge from a domestic wastewater treatment plant, river sediment,
      anaerobic digestion sludge and nitrifying enrichment culture. We assessed the
      suitability of the extraction procedures based on both DNA yield and quality. DNA
      quantification was performed by both ultra violet (UV) spectrophotometry and
      fluorescence spectrophotometry after staining with PicoGreen. In our study, DNA
      yields based on UV measurement were overestimated in most cases while DNA yields
      from fluorescence measurements correlated well with the sample load on agarose
      gels of crude DNA. The quality of the DNA extracts was determined by gel
      electrophoresis of crude DNA and PCR products from 16S rDNA with the universal
      primer set 27f/1525r. It was observed that gel electrophoresis of crude DNA was
      not always suitable to evaluate DNA integrity and purity since interfering
      background substances (e.g. humic substances) were not visible. Therefore, we
      strongly recommend examining the DNA quality of both crude DNA and 16S rDNA PCR
      products by gel electrophoresis when a new extraction method is established.
      Summarizing, we found four out of ten extraction procedures being applicable to
      all tested samples without noticeable restrictions. The procedure G (according to
      the standard method 432_10401 of the Lower Saxony State Office for Consumer
      Protection and Food Safety) had the broadest application range over procedure J
      (published by Wilson, 2001). These were followed by procedures F (Singka et al.,
      2012) and A (Bourrain et al., 1999). All four extraction procedures delivered
      reliable and reproducible crude DNA and PCR products. From an economical point of
      view, all procedures tested during this study were cheaper compared to commercial
      DNA extraction kits.

PMID- 29056448
TI  - Evolution of the glucagon-like system across fish.
AB  - In fishes, including the jawless lampreys, the most ancient lineage of extant
      vertebrates, plasma glucose levels are highly variable and regulation is more
      relaxed than in mammals. The regulation of glucose and lipid in fishes in common
      with mammals involves members of the glucagon (GCG)-like family of
      gastrointestinal peptides. In mammals, four peptides GCG, glucagon-like peptide 1
      and 2 (GLP1 and GLP2) and glucose-dependent insulinotropic peptide (GIP) that
      activate four specific receptors exist. However, in lamprey and other fishes the
      glucagon-like family evolved differently and they retained additional gene family
      members (glucagon-related peptide, gcrp and its receptor, gcrpr) that are absent
      from mammals. In the present study, we analysed the evolution of the glucagon
      like system in fish and characterized gene expression of the family members in
      the European sea bass (Dicentrarchus labrax) a teleost fish. Phylogenetic
      analysis revealed that multiple receptors and peptides of the glucagon-like
      family emerged early during the vertebrate radiation and evolved via lineage
      specific events. Synteny analysis suggested that family member gene loss is
      likely to be the result of a single gene deletion event. Lamprey was the only
      fish where a putative glp1r persisted and the presence of the receptor gene in
      the genomes of the elephant shark and coelacanth remains unresolved. In the
      coelacanth and elephant shark, unique proglucagon genes were acquired which in
      the former only encoded Gcg and Glp2 and in the latter, shared a similar
      structure to the teleost proglucagon gene but possessed an extra exon coding for
      Glp-like peptide that was most similar to Glp2. The variable tissue distribution
      of the gene transcripts encoding the ligands and receptors of the glucagon-like
      system in an advanced teleost, the European sea bass, suggested that, as occurs
      in mammals, they have acquired distinct functions. Statistically significant (p <
      .05) down-regulation of teleost proglucagon a in sea bass with modified plasma
      glucose levels confirmed the link between these peptides and metabolism. The
      tissue distribution of members of the glucagon-like system in sea bass and human
      suggests that evolution of the brain-gut-peptide regulatory loop diverged between
      teleosts and mammals despite the overall conservation and similarity of glucagon
      like family members.

PMID- 29056449
TI  - Venous disease patient registries available in the United States.
AB  - Patient registries are beneficial in that they allow the collection of
      prospective data focused on a specific medical issue. These registries give
      providers a "real-world" view of patient outcomes. Many medical disciplines have
      a long history of developing and using patient registries; the first patient
      registry for chronic venous disease in the United States was launched in 2011,
      fairly recently in comparison. Registries included in this review were identified
      by surveying members of major academic societies that focus on the care of
      chronic venous disease and by searching MEDLINE and Embase databases using Ovid
      interface. Medical directors of four of the five databases available in the
      United States completed a standard questionnaire, and the answers served as the
      basis for this review. This review is not a comparison of registries; it does,
      however, describe the common and unique features of four venous registries
      currently available in the United States with the purpose of increasing awareness
      of and fostering participation in these registries.

PMID- 29056450
TI  - Late rDNA Condensation Ensures Timely Cdc14 Release and Coordination of Mitotic
      Exit Signaling with Nucleolar Segregation.
AB  - The nucleolus plays a pivotal role in multiple key cellular processes. An
      illustrative example is the regulation of mitotic exit in Saccharomyces
      cerevisiae through the nucleolar sequestration of the Cdc14 phosphatase. The
      peculiar structure of the nucleolus, however, has also its drawbacks. The
      repetitive nature of the rDNA gives rise to cohesion-independent linkages whose
      resolution in budding yeast requires the Cdc14-dependent inhibition of rRNA
      transcription, which facilitates condensin accessibility to this locus. Thus, the
      rDNA condenses and segregates later than most other yeast genomic regions. Here,
      we show that defective function of a small nucleolar ribonucleoprotein particle
      (snoRNP) assembly factor facilitates condensin accessibility to the rDNA and
      induces nucleolar hyper-condensation. Interestingly, this increased compaction of
      the nucleolus interferes with the proper release of Cdc14 from this organelle.
      This observation provides an explanation for the delayed rDNA condensation in
      budding yeast, which is necessary to efficiently coordinate timely Cdc14 release
      and mitotic exit with nucleolar compaction and segregation.

PMID- 29056451
TI  - The Lamprey Pallium Provides a Blueprint of the Mammalian Layered Cortex.
AB  - The basic architecture of the mammalian neocortex is remarkably similar across
      species. Pallial structures in the reptilian brain are considered amniote
      precursors of mammalian neocortex, whereas pallia of anamniotes ("lower"
      vertebrates) have been deemed largely insignificant with respect to homology.
      Here, we examine the cytoarchitecture of the lateral pallium in the lamprey, the
      phylogenetically oldest group of extant vertebrates. We reveal a three-layered
      structure with similar excitatory cell types as in the mammalian cortex and
      GABAergic interneurons. The ventral parts are sensory areas receiving
      monosynaptic thalamic input that can be activated from the optic nerve, whereas
      the dorsal parts contain motor areas with efferent projections to the brainstem,
      receiving oligosynaptic thalamic input. Both regions receive monosynaptic
      olfactory input. This three-layered "primordial" lamprey lateral pallium has
      evolved most features of the three-layered reptilian cortices and is thereby a
      precursor of the six-layered "neo" cortex with a long-standing evolutionary
      precedent (some 500 million years ago).

PMID- 29056452
TI  - Spike Burst Coding of Translatory Optic Flow and Depth from Motion in the Fly
      Visual System.
AB  - Many animals use the visual motion generated by traveling straight-the
      translatory optic flow-to successfully navigate obstacles: near objects appear
      larger and to move more quickly than distant objects. Flies are expert at
      navigating cluttered environments, and while their visual processing of rotatory
      optic flow is understood in exquisite detail, how they process translatory optic
      flow remains a mystery. We present novel cell types that have local motion
      receptive fields matched to translation self-motion, the vertical translation
      (VT) cells. One of these, the VT1 cell, encodes self-motion in the forward
      sideslip direction and fires action potentials in spike bursts as well as single
      spikes. We show that the spike burst coding is size and speed-tuned and is
      selectively modulated by motion parallax-the relative motion experienced during
      translation. These properties are spatially organized, so that the cell is most
      excited by clutter rather than isolated objects. When the fly is presented with a
      simulation of flying past an elevated object, the spike burst activity is
      modulated by the height of the object, and the rate of single spikes is
      unaffected. When the moving object alone is experienced, the cell is weakly
      driven. Meanwhile, the VT2-3 cells have motion receptive fields matched to the
      lift axis. In conjunction with previously described horizontal cells, the VT
      cells have properties well suited to the visual navigation of clutter and to
      encode the fly's movements along near cardinal axes of thrust, lift, and forward
      sideslip.

PMID- 29056453
TI  - Audiomotor Perceptual Training Enhances Speech Intelligibility in Background
      Noise.
AB  - Sensory and motor skills can be improved with training, but learning is often
      restricted to practice stimuli. As an exception, training on closed-loop (CL)
      sensorimotor interfaces, such as action video games and musical instruments, can
      impart a broad spectrum of perceptual benefits. Here we ask whether computerized
      CL auditory training can enhance speech understanding in levels of background
      noise that approximate a crowded restaurant. Elderly hearing-impaired subjects
      trained for 8 weeks on a CL game that, like a musical instrument, challenged them
      to monitor subtle deviations between predicted and actual auditory feedback as
      they moved their fingertip through a virtual soundscape. We performed our study
      as a randomized, double-blind, placebo-controlled trial by training other
      subjects in an auditory working-memory (WM) task. Subjects in both groups
      improved at their respective auditory tasks and reported comparable expectations
      for improved speech processing, thereby controlling for placebo effects. Whereas
      speech intelligibility was unchanged after WM training, subjects in the CL
      training group could correctly identify 25% more words in spoken sentences or
      digit sequences presented in high levels of background noise. Numerically, CL
      audiomotor training provided more than three times the benefit of our subjects'
      hearing aids for speech processing in noisy listening conditions. Gains in speech
      intelligibility could be predicted from gameplay accuracy and baseline inhibitory
      control. However, benefits did not persist in the absence of continuing practice.
      These studies employ stringent clinical standards to demonstrate that perceptual
      learning on a computerized audio game can transfer to "real-world" communication
      challenges.

PMID- 29056454
TI  - Evolutionary History of Saber-Toothed Cats Based on Ancient Mitogenomics.
AB  - Saber-toothed cats (Machairodontinae) are among the most widely recognized
      representatives of the now largely extinct Pleistocene megafauna. However, many
      aspects of their ecology, evolution, and extinction remain uncertain. Although
      ancient-DNA studies have led to huge advances in our knowledge of these aspects
      of many other megafauna species (e.g., mammoths and cave bears), relatively few
      ancient-DNA studies have focused on saber-toothed cats [1-3], and they have been
      restricted to short fragments of mitochondrial DNA. Here we investigate the
      evolutionary history of two lineages of saber-toothed cats (Smilodon and
      Homotherium) in relation to living carnivores and find that the Machairodontinae
      form a well-supported clade that is distinct from all living felids. We present
      partial mitochondrial genomes from one S. populator sample and three Homotherium
      sp. samples, including the only Late Pleistocene Homotherium sample from Eurasia
      [4]. We confirm the identification of the unique Late Pleistocene European fossil
      through ancient-DNA analyses, thus strengthening the evidence that Homotherium
      occurred in Europe over 200,000 years later than previously believed. This in
      turn forces a re-evaluation of its demography and extinction dynamics. Within the
      Machairodontinae, we find a deep divergence between Smilodon and Homotherium (~18
      million years) but limited diversity between the American and European
      Homotherium specimens. The genetic data support the hypothesis that all Late
      Pleistocene (or post-Villafrancian) Homotherium should be considered a single
      species, H. latidens, which was previously proposed based on morphological data
      [5, 6].

PMID- 29056455
TI  - Genetic Coupling of Female Mate Choice with Polygenic Ecological Divergence
      Facilitates Stickleback Speciation.
AB  - Ecological speciation with gene flow is widespread in nature [1], but it presents
      a conundrum: how are associations between traits under divergent natural
      selection and traits that contribute to assortative mating maintained?
      Theoretical models suggest that genetic mechanisms inhibiting free recombination
      between loci underlying these two types of traits (hereafter, "genetic coupling")
      can facilitate speciation [2-4]. Here, we perform a direct test for genetic
      coupling by mapping both divergent traits and female mate choice in a classic
      model of ecological speciation: sympatric benthic and limnetic threespine
      stickleback (Gasterosteus aculeatus). By measuring mate choice in F2 hybrid
      females, we allowed for recombination between loci underlying assortative mating
      and those under divergent ecological selection. In semi-natural mating arenas in
      which females had access to both benthic and limnetic males, we found that F2
      females mated with males similar to themselves in body size and shape. In
      addition, we found two quantitative trait loci (QTLs) associated with female mate
      choice that also predicted female morphology along the benthic-limnetic trait
      axis. Furthermore, a polygenic genetic model that explains adaptation to
      contrasting benthic and limnetic feeding niches [5] also predicted F2 female mate
      choice. Together, these results provide empirical evidence that genetic coupling
      of assortative mating with traits under divergent ecological selection helps
      maintain species in the face of gene flow, despite a polygenic basis for
      adaptation to divergent environments.

PMID- 29056456
TI  - Re-creation of a Key Step in the Evolutionary Switch from C3 to C4 Leaf Anatomy.
AB  - The C4 photosynthetic pathway accounts for ~25% of primary productivity on the
      planet despite being used by only 3% of species. Because C4 plants are higher
      yielding than C3 plants, efforts are underway to introduce the C4 pathway into
      the C3 crop rice. This is an ambitious endeavor; however, the C4 pathway evolved
      from C3 on multiple independent occasions over the last 30 million years, and
      steps along the trajectory are evident in extant species. One approach toward
      engineering C4 rice is to recapitulate this trajectory, one of the first steps of
      which was a change in leaf anatomy. The transition from C3 to so-called "proto
      Kranz" anatomy requires an increase in organelle volume in sheath cells
      surrounding leaf veins. Here we induced chloroplast and mitochondrial development
      in rice vascular sheath cells through constitutive expression of maize GOLDEN2
      LIKE genes. Increased organelle volume was accompanied by the accumulation of
      photosynthetic enzymes and by increased intercellular connections. This suite of
      traits reflects that seen in "proto-Kranz" species, and, as such, a key step
      toward engineering C4 rice has been achieved.

PMID- 29056458
TI  - Life on the driveline: Molecular detection and fluorescence in situ hybridization
      based visualization of microbial species in patients with left ventricular assist
      devices.

PMID- 29056459
TI  - Low-flow support of the chronic pressure-overloaded right ventricle induces
      reversed remodeling.
AB  - BACKGROUND: Mechanical right ventricular (RV) support in pulmonary arterial
      hypertension patients has been feared to cause pulmonary hemorrhage and to be
      detrimental for the after-load-sensitive RV. Continuous low-flow pumps offer
      promise but remain insufficiently tested. METHODS: The pulmonary artery was
      banded in 20 sheep in this study. Eight weeks later, a Synergy micro-pump
      (HeartWare International, Framingham MA) was inserted in 10 animals, driving
      blood from the right atrium to the pulmonary artery. After magnetic resonance
      imaging, hemodynamics and RV pressure-volume loop data were recorded. Eight weeks
      later, RV function was assessed in the same way, followed by histologic analysis
      of the ventricular tissue. RESULTS: During the 8 weeks of support, RV volumes and
      central venous pressure decreased significantly, whereas RV contractility
      increased. Pulmonary artery pressure increased modestly, particularly its
      diastolic component. RV contribution to total right-sided cardiac output
      increased from 12 +/- 12% to 41 +/- 9% (p < 1 * 10-4). After pump inactivation,
      and compared with 8 weeks earlier, RV volumes had significantly decreased,
      tricuspid valve regurgitation had almost disappeared, and RV contractility had
      significantly increased, resulting in significantly increased RV forward power
      (0.25 +/- 0.05 vs 0.16 +/- 0.06 W, p = 0.014). Fulton index and RV myocyte size
      were significantly smaller, and without changes in fibrosis, when compared with
      controls. CONCLUSIONS: Prolonged continuous low-flow RV mechanical support
      significantly unloads the chronic pressure-overloaded RV and improves cardiac
      output. After 8 weeks, RV hemodynamic recovery and reverse remodeling begin to
      occur, without increased fibrosis.

PMID- 29056457
TI  - Vibrio cholerae Combines Individual and Collective Sensing to Trigger Biofilm
      Dispersal.
AB  - Bacteria can generate benefits for themselves and their kin by living in
      multicellular, matrix-enclosed communities, termed biofilms, which are
      fundamental to microbial ecology and the impact bacteria have on the environment,
      infections, and industry [1-6]. The advantages of the biofilm mode of life
      include increased stress resistance and access to concentrated nutrient sources
      [3, 7, 8]. However, there are also costs associated with biofilm growth,
      including the metabolic burden of biofilm matrix production, increased resource
      competition, and limited mobility inside the community [9-11]. The decision
      making strategies used by bacteria to weigh the costs between remaining in a
      biofilm or actively dispersing are largely unclear, even though the dispersal
      transition is a central aspect of the biofilm life cycle and critical for
      infection transmission [12-14]. Using a combination of genetic and novel single
      cell imaging approaches, we show that Vibrio cholerae integrates dual sensory
      inputs to control the dispersal response: cells use the general stress response,
      which can be induced via starvation, and they also integrate information about
      the local cell density and molecular transport conditions in the environment via
      the quorum sensing apparatus. By combining information from individual (stress
      response) and collective (quorum sensing) avenues of sensory input, biofilm
      dwelling bacteria can make robust decisions to disperse from large biofilms under
      distress, while preventing premature dispersal when biofilm populations are
      small. These insights into triggers and regulators of biofilm dispersal are a key
      step toward actively inducing biofilm dispersal for technological and medical
      applications, and for environmental control of biofilms.

PMID- 29056460
TI  - Use of a percutaneous temporary circulatory support device as a bridge to
      decision during acute decompensation of advanced heart failure.
AB  - BACKGROUND: Prognosis is poor for patients with decompensated advanced heart
      failure (HF) refractory to medical therapy. Evaluating candidacy for durable
      mechanical circulatory support (MCS), cardiac transplantation, or palliative care
      is complex, and time is often needed to stabilize the patient hemodynamically.
      The Impella 5.0 (Abiomed, Danvers, MA) is a minimally invasive axial-flow
      catheter capable of providing full temporary hemodynamic support. We report a
      multicenter series on the use of this device for bridge to decision (BTD) in
      decompensated advanced HF patients. METHODS: In a retrospective evaluation at 3
      centers of patients with advanced HF who acutely decompensated and received the
      Impella 5.0 for BTD, we analyzed demographics, procedural characteristics, in
      hospital and intermediate-term outcomes, and in-hospital complications. RESULTS:
      There were 58 patients who met inclusion criteria from 2010 to 2015. All were
      inotrope dependent. The mean ejection fraction was 13%, and median age was 59
      years (interquartile range, 48-64 years). Mean duration of support was 7 days
      (range, 0-22 days). Thirty-nine patients survived to next therapy (67%), with
      most receiving durable MCS (n = 20) or heart transplantation (n = 15). In
      hospital complications included bleeding (n = 9) and hemolysis (n = 4). Of
      patients who survived to the next therapy, 1-year survival was 65% for those who
      received durable MCS, 87% for those who received a transplant, and 75% for those
      who were stabilized and weaned. CONCLUSIONS: The Impella 5.0 may provide a BTD
      strategy for patients with advanced HF and acute hemodynamic instability.
      Prospective studies are needed to evaluate the safety and effectiveness of this
      device in this patient population.

PMID- 29056461
TI  - Two Disease-Causing SNAP-25B Mutations Selectively Impair SNARE C-terminal
      Assembly.
AB  - Synaptic exocytosis relies on assembly of three soluble N-ethylmaleimide
      sensitive factor attachment receptor (SNARE) proteins into a parallel four-helix
      bundle to drive membrane fusion. SNARE assembly occurs by stepwise zippering of
      the vesicle-associated SNARE (v-SNARE) onto a binary SNARE complex on the target
      plasma membrane (t-SNARE). Zippering begins with slow N-terminal association
      followed by rapid C-terminal zippering, which serves as a power stroke to drive
      membrane fusion. SNARE mutations have been associated with numerous diseases,
      especially neurological disorders. It remains unclear how these mutations affect
      SNARE zippering, partly due to difficulties to quantify the energetics and
      kinetics of SNARE assembly. Here, we used single-molecule optical tweezers to
      measure the assembly energy and kinetics of SNARE complexes containing single
      mutations I67T/N in neuronal SNARE synaptosomal-associated protein of 25kDa (SNAP
      25B), which disrupt neurotransmitter release and have been implicated in
      neurological disorders. We found that both mutations significantly reduced the
      energy of C-terminal zippering by ~10 kBT, but did not affect N-terminal
      assembly. In addition, we observed that both mutations lead to unfolding of the C
      terminal region in the t-SNARE complex. Our findings suggest that both SNAP-25B
      mutations impair synaptic exocytosis by destabilizing SNARE assembly, rather than
      stabilizing SNARE assembly as previously proposed. Therefore, our measurements
      provide insights into the molecular mechanism of the disease caused by SNARE
      mutations.

PMID- 29056462
TI  - The SARS-CoV Fusion Peptide Forms an Extended Bipartite Fusion Platform that
      Perturbs Membrane Order in a Calcium-Dependent Manner.
AB  - Coronaviruses (CoVs) are a major infectious disease threat and include the
      pathogenic human pathogens of zoonotic origin: severe acute respiratory syndrome
      CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Entry of CoVs
      into host cells is mediated by the viral spike (S) protein, which is structurally
      categorized as a class I viral fusion protein, within the same group as influenza
      virus and HIV. However, S proteins have two distinct cleavage sites that can be
      activated by a much wider range of proteases. The exact location of the CoV
      fusion peptide (FP) has been disputed. However, most evidence suggests that the
      domain immediately downstream of the S2' cleavage site is the FP (amino acids 798
      818 SFIEDLLFNKVTLADAGFMKQY for SARS-CoV, FP1). In our previous electron spin
      resonance spectroscopic studies, the membrane-ordering effect of influenza virus,
      HIV, and Dengue virus FPs has been consistently observed. In this study, we used
      this effect as a criterion to identify and characterize the bona fide SARS-CoV
      FP. Our results indicate that both FP1 and the region immediately downstream
      (amino acids 816-835 KQYGECLGDINARDLICAQKF, FP2) induce significant membrane
      ordering. Furthermore, their effects are calcium dependent, which is consistent
      with in vivo data showing that calcium is required for SARS-CoV S-mediated
      fusion. Isothermal titration calorimetry showed a direct interaction between
      calcium cations and both FPs. This Ca2+-dependency membrane ordering was not
      observed with influenza FP, indicating that the CoV FP exhibits a mechanistically
      different behavior. Membrane-ordering effects are greater and penetrate deeper
      into membranes when FP1 and FP2 act in a concerted manner, suggesting that they
      form an extended fusion "platform."

PMID- 29056463
TI  - A high jugular bulb and poor development of perivestibular aqueductal air cells
      are not the cause of endolymphatic hydrops in patients with Meniere's disease.
AB  - OBJECTIVE: The presence of endolymphatic hydrops in the inner ear, which can be
      detected with gadolinium-enhanced magnetic resonance imaging (Gd-MRI), is widely
      recognized as the main pathological cause of Meniere's disease (MD). However, the
      precise mechanisms underlying the development of endolymphatic hydrops remains
      unclear. One hypothesis proposes a relationship between the presence of a high
      jugular bulb (HJB) and MD, which disrupts the vestibular aqueduct leading to the
      development of endolymphatic hydrops. This study sought to identify anatomical
      features in MD patients using computed tomography (CT) images of the temporal
      bone. METHODS: Fifty-nine MD patients meeting the AAO-HNS diagnostic criteria and
      exhibiting endolymphatic hydrops in Gd-MRI were enrolled between July 2009 and
      December 2015. We only included MD patients who showed unilateral endolymphatic
      hydrops in Gd-MRI. Sixty-six patients with otosclerosis or facial palsy were also
      enrolled as control participants. In both groups, patients with other pathologies
      (e.g., chronic otitis media or cholesteatoma) and patients <16years old were
      excluded. HJB was defined as a JB that was observable in the axial CT image at
      the level where the round window could be visualized. JB surface area was
      measured on the axial image at the level where the foramen spinosum could be
      visualized. Finally, to investigate the relationship between the pneumatization
      of perivestibular aqueductal air cells and the existence of endolymphatic
      hydrops, the development of the air cells was rated using a three-grade
      evaluation system and the distance between the posterior semicircular canal
      (PSCC) and the posterior fossa dura was measured. RESULTS: The presence of HJB
      was observed in 22 of 59 affected sides of MD patients and in 17 healthy sides.
      The likelihood that HJB was detected on an affected side (22/39) was not
      significantly above chance (50%). The HJB detection rate did not significantly
      differ between the three groups (MD affected side, MD healthy side, and control
      patients). Furthermore, there were no significant group differences in JB surface
      area, distance between the PSCC and posterior fossa dura, or the development of
      perivestibular aqueductal air cells. CONCLUSION: We did not find any relationship
      between the anatomy of the temporal bones and the existence of endolymphatic
      hydrops. Moreover, we found no evidence suggesting that HJB or poor development
      of perivestibular aqueductal air cells were the cause of endolymphatic hydrops in
      MD patients.

PMID- 29056464
TI  - A population-based comparison of European and North American sinonasal cancer
      survival.
AB  - OBJECTIVE: Sinonasal cancers (SNC) are rare, thus limiting previous prognostic
      studies on a multinational level. The aim of this study is to utilize two
      population-based datasets to compare prognoses for SNC between the United States
      (US) and Europe. METHODS: The European Cancer Registry (EUROCARE) database and
      the United States National Cancer Institute's Surveillance, Epidemiology, and End
      Results (SEER) database were searched to identify survival of patients diagnosed
      with SNC between 1990 and 2007. Relative survival (RS) data were stratified by
      age group, gender, geographic location, and diagnostic time period. RESULTS:
      12,541 SNC cases were identified in EUROCARE, while SEER identified 4,312. Males
      comprised the majority in Europe (62.3%) and the US (58.3%). Most patients were
      over 55 years in Europe (77.0%) and the US (69.5%). Age over 75 was a
      statistically significant poor prognostic indicator for 5-year RS in the US
      (48.2%; 95% CI=[43.9, 52.4]) and Europe (38.5%; [34.7, 42.7]). Female gender
      imparted a favorable 5-year RS in all regions except in Central Europe. By
      region, the US had the highest 5-year RS (58.8%; [56.4, 61.1]) and Eastern Europe
      had the lowest 5-year RS (37.1%; [34.0, 40.6]). The aggregate European 5-year RS
      was 48.1% [46.4, 49.8]. CONCLUSION: SNC in Europe and the US most commonly
      affects males and individuals over the age of 55 years. Male gender and age over
      75 are poor prognostic factors at 5 years. Five-year RS in the US is higher than
      the 5-year European aggregate RS.

PMID- 29056466
TI  - Gastroprotective effects and structural characterization of a pectic fraction
      isolated from Artemisia campestris subsp maritima.
AB  - The aim of this study was to investigate the chemical structure and biological
      activity of a pectic fraction isolated from the aerial parts of A. campestris L.
      subsp. maritima Arcangeli. The chemical and spectroscopic analyses of the pectic
      fraction (ACP-E10) demonstrated that ACP-E10 was composed of homogalacturonan
      (HG) (60%) and rhamnogalacturonan-I (RG-I) (29%) regions. Side chains of the RG-I
      included mainly branched arabinans and type II arabinogalactans (AG-II). The
      molar mass of ACP-E10 determined by HPSEC-MALLS was 16,600g/mol. ACP-E10 was
      evaluated for its gastroprotective effect against ethanol-induced gastric lesions
      in rats. Oral pretreatment of animals with ACP-E10 (0.3, 3 and 30mg/kg)
      significantly reduced gastric lesions by 77+/-7.9%, 55+/-11.1% and 65+/-11.8%.
      ACP-E10 also maintained mucus and glutathione (GSH) contents in the gastric
      mucosa. In addition, ACP-E10 demonstrated antioxidant activity in vitro by the
      DPPH assay. These results demonstrated that the pectin from A. campestris had
      significant gastroprotective effects in vivo, which were likely attributable to
      their capacity to increase the protective defenses of gastric mucosa.

PMID- 29056467
TI  - Gold laced bio-macromolecules for theranostic application.
AB  - Gold nanostructures are promising entities for various biomedical applications,
      due to their promising physical and optical properties. They can be tailored in
      different sizes and shapes to play vital roles for photothermal therapy,
      Biosensing, in vivo X-ray/CT contrast etc. Many biomacromolecules have been used
      for chemical reduction of ionic gold into zero-valent metallic nanoparticles of
      specific shape/size followed by stabilizing them for long term utilization. This
      review will sum up a range of biomacromolecules including Alginate, Agarose,
      Starch, Carragenan, Cellulose, Chitin, Chitosan, Collagen, Cyclodextrins,
      Chondrotin Sulfate, Dextran Sulfate, Fucoidan, Gelatin, Guar Gum and Hyaluronic
      Acid, whose functionalities have been explored in combination with gold
      nanoparticles for various biomedical applications.

PMID- 29056465
TI  - Modified Dioscorea hispida starch-based hydrogels and their in-vitro cytotoxicity
      study on small intestine cell line (FHS-74 Int).
AB  - Starch-based hydrogels are promising smart materials for biomedical and
      pharmaceutical applications, which offer exciting perspectives in biophysical
      research at molecular level. This work was intended to develop, characterize and
      explore the properties of hydrogel from starch extracted from new source,
      Dioscorea hispida Dennst. Starch-mediated hydrogels were successfully synthesized
      via free radical polymerization method with varying concentrations of acrylic
      acid (AA),N,N'-methylenebisacrylamide (MBA) and sodium hydroxide (NaOH) in
      aqueous system. The grafting reaction between starch and AA was examined by
      observing the decline in intensity peak of hydrogel FTIR spectrum at 3291cm-1 and
      peak around 1600-1680cm-1, indicating the stretching of hydroxyl group (OH) and
      stretching of carbon-carbon double bond (CC) respectively. The effects of cross
      linker, monomer and NaOH concentration on swelling ratio and gel content in
      different medium and conditions were also evaluated. The thermal stability and
      structural morphology of as-synthesized hydrogels were studied by
      thermogravimetry analysis (TGA) and scanning electron microscopy (SEM). In-vitro
      cytotoxicity study using small intestine cell line (FHS-74 Int) revealed that the
      as-formulated eco-friendly-hydrogel was free from any harmful material and safe
      to use for future product development.

PMID- 29056468
TI  - Interactive relations of type 2 diabetes and abdominal obesity to cognitive
      impairment: A cross-sectional study in rural area of Xi'an in China.
AB  - AIMS: Type 2 diabetes and obesity, which are frequently comorbid, have been
      associated with cognitive impairment. We aim to examine the potential modulating
      effect between obesity and diabetes on cognitive impairment. METHODS: We
      recruited 865 adults (aged >=55years) lived in a village of Xi'an in China from
      October 2014 to March 2015. All participants underwent biomedical and
      neuropsychological assessment. Relations of diabetes and abdominal obesity to
      cognitive impairment were examined in multiple regression models. RESULTS: A
      total of 155 participants (17.9%) presented with the diagnosis of cognitive
      impairment. Diabetes or obesity alone wasn't significantly associated with
      cognitive impairment. Interaction analysis showed a significant interaction
      between abdominal obesity and diabetes on cognitive impairment. Stratified
      multivariate analysis revealed that the association between diabetes and
      cognitive impairment was positive in participants with abdominal obesity (OR
      2.436, 95% CI 1.345-4.411, p=0.003, in diabetics with high WC, and OR 2.348, 95%
      CI 1.373-4.014, p=0.002, in diabetics with high WHR), but negative in those
      without abdominal obesity. CONCLUSIONS: Type 2 diabetes interacts with abdominal
      obesity to be associated with an increased risk of cognitive impairment by more
      than two times.

PMID- 29056469
TI  - Intrauterine Bakri Balloon and Vaginal Tamponade Combined with Abdominal
      Compression for the Management of Postpartum Hemorrhage.
AB  - OBJECTIVE: This study sought to investigate the effect of Bakri balloon use and
      vaginal tamponade combined with abdominal compression for the management of
      postpartum hemorrhage (PPH). METHODS: This retrospective study reviewed cases of
      PPH in the International Peace Maternal and Child Health Hospital of China
      Welfare Institution in Shanghai, China from January 1, 2010 to December 31, 2015.
      A single use of the intrauterine Bakri balloon was applied in some cases, and
      additional vaginal tamponade combined with abdominal compression (double
      compression) was applied in other cases. The authors evaluated the effect of
      these two methods in the management of PPH. RESULTS: The Bakri balloon was used
      in 305 cases of intrauterine PPH, and the clinical efficacy was 93.26%. One group
      of study patients underwent double compression, and these patients had a better
      clinical efficacy rate of 96.3% (157 of 163), whereas the efficacy in cases using
      the Bakri balloon alone (control group) was 87.3% (124 of 142). The postoperative
      complication rates of these two groups were 9.4% and 8.7%, respectively. Uterine
      arterial embolization was performed in patients in whom Bakri balloon use failed.
      None of the cases resulted in a hysterectomy. CONCLUSION: Intrauterine Bakri
      balloon use combined with vaginal tamponade and abdominal compression is more
      effective in the treatment of PPH compared with Bakri balloon use alone. This
      method does not increase postoperative complications. Uterine atony with placenta
      previa or implantation may be possible reasons for noneffectiveness of Bakri
      balloon use.

PMID- 29056470
TI  - Phase 2 Open-Label Study of Bortezomib, Cladribine, and Rituximab in Advanced,
      Newly Diagnosed, and Relapsed/Refractory Mantle-Cell and Indolent Lymphomas.
AB  - BACKGROUND: Mantle-cell lymphoma (MCL) and indolent non-Hodgkin lymphoma (iNHL)
      are incurable heterogeneous diseases characterized by relapse. There is a need
      for newer treatments in MCL and iNHL, especially in the relapsed/refractory (R/R)
      setting. We therefore investigated the novel combination of bortezomib (Velcade),
      cladribine, and rituximab (VCR) in front-line and R/R settings in MCL and iNHL
      (NCT00980395). PATIENTS AND METHODS: Eligible patients included adults with
      biopsy-proven CD20-positive MCL and iNHL who met the criteria for treatment.
      Rituximab 375 mg/m2 intravenous (IV) day 1, cladribine 4 mg/m2 IV days 1 to 5,
      and bortezomib 1.3 mg/m2 IV days 1 and 4 were administered every 28 days for 6
      cycles. RESULTS: Twenty-four patients were enrolled onto the study with a median
      follow-up of 38.5 months. Median age was 66.5 years, and 46% had MCL. The most
      common adverse events were hematologic, with febrile neutropenia in 3 patients.
      Neuropathy was noted in 17% of patients, of which 8% was grade 3 or above. The
      overall response rate was 92%. For the entire cohort, and for MCL patients, the
      median progression-free survival and the median overall survival were not
      reached. The 2-year progression-free survival was 82% for the MCL group and 54%
      for the iNHL group; it was 80% for treatment-naive patients and 57% for R/R
      patients. CONCLUSION: VCR is effective in MCL and iNHL. Although hematologic
      toxicity can be an issue, this study demonstrates a high response rate to a novel
      combination and provides an alternative option in transplant-ineligible R/R MCL
      and iNHL.

PMID- 29056471
TI  - Re: Daniel E. Spratt, Robert T. Dess, Zachary S. Zumsteg, et al. A Systematic
      Review and Framework for the Use of Hormone Therapy with Salvage Radiation
      Therapy for Recurrent Prostate Cancer. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2017.06.027.

PMID- 29056472
TI  - Contribution of lectin-like oxidized low-density lipoprotein receptor-1 and LOX-1
      modulating compounds to vascular diseases.
AB  - The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major
      receptor for binding and uptake of oxidized low-density lipoprotein (oxLDL) in
      endothelial cells. LOX-1 is also expressed in macrophages, smooth muscle cells
      and platelets. Following internalization of oxLDL, LOX-1 initiates a vicious
      cycle from activation of pro-inflammatory signaling pathways, thus promoting an
      increased reactive oxygen species formation and secretion of pro-inflammatory
      cytokines. LOX-1 plays a pivotal role in the development of endothelial
      dysfunction, foam cell and advanced lesions formation as well as in myocardial
      ischemia. Furthermore, it is known that LOX-1 plays a pivotal role in
      mitochondrial DNA damage, vascular cell apoptosis, and autophagy. A large number
      of studies provide evidence of a LOX-1's role in endothelial dysfunction,
      hypertension, diabetes, and obesity. In addition, novel insights into LOX-1
      ligands and the activated signaling pathways have been gained. Recent studies
      have shown an interaction of LOX-1 with microRNA's, thus providing novel tools to
      regulate LOX-1 function. Because LOX-1 is increased in atherosclerotic plaques
      and contributes to endothelial dysfunction, several compounds were tested in vivo
      and in vitro to modulate the LOX-1 expression in therapeutic approaches.

PMID- 29056473
TI  - Potential and limitations of Klebsiella pneumoniae as a microbial cell factory
      utilizing glycerol as the carbon source.
AB  - Klebsiella pneumoniae is a Gram-negative facultative anaerobe that metabolizes
      glycerol efficiently under both aerobic and anaerobic conditions. This microbe is
      considered an outstanding biocatalyst for transforming glycerol into a variety of
      value-added products. Crude glycerol is a cheap carbon source and can be
      converted by K. pneumoniae into useful compounds such as lactic acid, 3
      hydroxypropionic acid, ethanol, 1,3-propanediol, 2,3-butanediol, and succinic
      acid. This review summarizes glycerol metabolism in K. pneumoniae and its
      potential as a microbial cell factory for the production of commercially
      important acids and alcohols. Although many challenges remain, K. pneumoniae is a
      promising workhorse when glycerol is used as the carbon source.

PMID- 29056474
TI  - Next generation organoids for biomedical research and applications.
AB  - Organoids are in vitro cultures of miniature fetal or adult organ-like
      structures. Their potentials for use in tissue and organ replacement, disease
      modeling, toxicology studies, and drug discovery are tremendous. Currently, major
      challenges facing human organoid technology include (i) improving the range of
      cellular heterogeneity for a particular organoid system, (ii) mimicking the
      native micro- and matrix-environment encountered by cells within organoids, and
      (iii) developing robust protocols for the in vitro maturation of organoids that
      remain mostly fetal-like in cultures. To tackle these challenges, we advocate the
      principle of reverse engineering that replicates the inner workings of in vivo
      systems with the goal of achieving functionality and maturation of the resulting
      organoid structures with the input of minimal intrinsic (cellular) and
      environmental (matrix and niche) constituents. Here, we present an overview of
      organoid technology development in several systems that employ cell materials
      derived from fetal and adult tissues and pluripotent stem cell cultures. We focus
      on key studies that exploit the self-organizing property of embryonic progenitors
      and the role of designer matrices and cell-free scaffolds in assisting organoid
      formation. We further explore the relationship between adult stem cells, niche
      factors, and other current developments that aim to enhance robust organoid
      maturation. From these works, we propose a standardized pipeline for the
      development of future protocols that would help generate more physiologically
      relevant human organoids for various biomedical applications.

PMID- 29056475
TI  - Immunofluorescent detection in the ovary of host antibodies against a secretory
      ferritin injected into female Haemaphysalis longicornis ticks.
AB  - Due to the continuous threat of ticks and tick-borne diseases to human and animal
      health worldwide, and the drawbacks of chemical acaricide application, many
      researchers are exploring vaccination as an alternative tick control method.
      Earlier studies have shown that host antibodies can circulate in the ticks, but
      it has not been confirmed whether these antibodies can be passed on to the eggs.
      We previously reported that ticks infesting rabbits immunized with a recombinant
      secretory ferritin of Haemaphysalis longicornis (HlFER2) had reduced egg
      production and hatching. Here we attempted to detect the presence of antibodies
      against HlFER2 in the ovary and eggs of female ticks through immunofluorescent
      visualization. Purified anti-HlFER2 antibodies or rabbit IgG for control was
      directly injected to engorged female H. longicornis. Ovaries and eggs after
      oviposition were collected and prepared for an indirect immunofluorescent
      antibody test. Positive fluorescence was detected in ovaries one day post
      injection of anti-HlFER2 antibodies. Through silencing of Hlfer2 gene, we also
      determined whether the injected antibodies can specifically bind to native
      HlFER2. Immunofluorescence was observed in the oocytes of dsLuciferase control
      ticks injected with anti-HlFER2 antibodies, but not in the oocytes of Hlfer2
      silenced ticks also injected with anti-HlFER2 antibodies. Our current findings
      suggest that host antibodies can be passed on to the oocytes, which is
      significant in formulating a vaccine that can disrupt tick reproduction.

PMID- 29056476
TI  - Array-based sequencing of filaggrin gene for comprehensive detection of disease
      associated variants.

PMID- 29056477
TI  - Biliary complications among live donors following live donor liver
      transplantation.
AB  - INTRODUCTION: In live donor liver transplantation (LDLT), bile duct division is a
      critical step in donor hepatectomy. Biliary complications hence are a feared
      sequelae even among donors. Long term data on biliary complications in donors
      from India are sparse. METHODS: Prospective evaluation of 452 live donors over 10
      years was performed to ascertain the incidence & risk factors of clinically
      significant biliary complications. RESULTS: Of the 452 donor hepatectomies (M: F
      = 114:338, median age = 38), 66.2% (299) were extended right lobe grafts, 24.1%
      (109) modified right lobe and 9.7% (44) were left lobe grafts. Portal vein
      anatomy was Type-I in 85% (386), Type-II in 7.5% (34) and Type-III in 7.1% (32).
      Following donor hepatectomy, a single bile duct opening occurred only in 46.5%
      (210) of the grafts. Of the remaining 53.5% grafts, 2 ductal openings were noted
      in 217 (48%) and three ductal openings in 25 (5.5%). Incidence of multiple
      openings in the duct were more commonly noted in Type II (70.6%) and III (75%)
      portal vein anatomy than in grafts with Type I (50.4%) portal anatomy (P = 0.001)
      Bile leak was noted in 15 (3.3%) donors which included one broncho-biliary
      fistula and bilio-pleural fistula. Analysis revealed no association between post
      operative biliary complications and type of graft, portal vein anatomy or biliary
      anatomy. There was a single mortality in this series secondary to biliary sepsis.
      On long term follow, there were no biliary strictures in any of the patients.
      CONCLUSIONS: Biliary complications although rare (3.3%), present significant peri
      operative morbidity to the donors.

PMID- 29056479
TI  - Effect of combined stress (salinity and temperature) in European sea bass
      Dicentrarchus labrax osmoregulatory processes.
AB  - European sea bass Dicentrarchus labrax undertake seasonal migrations to estuaries
      and lagoons that are characterized by fluctuations in environmental conditions.
      Their ability to cope with these unstable habitats is undeniable, but it is still
      not clear how and to what extent salinity acclimation mechanisms are affected at
      temperatures higher than in the sea. In this study, juvenile sea bass were pre
      acclimated to seawater (SW) at 18 degrees C (temperate) or 24 degrees C (warm)
      for 2weeks and then transferred to fresh water (FW) or SW at the respective
      temperature. Transfer to FW for two weeks resulted in decreased blood
      osmolalities and plasma Cl- at both temperatures. In FW warm conditions, plasma
      Na+ was ~15% lower and Cl- was ~32% higher than in the temperate-water group.
      Branchial Na+/K+-ATPase (NKA) activity measured at the acclimation temperature
      (Vapparent) did not change according to the conditions. Branchial Na+/K+-ATPase
      activity measured at 37 degrees C (Vmax) was lower in warm conditions and
      increased in FW compared to SW conditions whatever the considered temperature.
      Mitochondrion-rich cell (MRC) density increased in FW, notably due to the
      appearance of lamellar MRCs, but this increase was less pronounced in warm
      conditions where MRC's size was lower. In SW warm conditions, pavement cell
      apical microridges are less developed than in other conditions. Overall gill
      morphometrical parameters (filament thickness, lamellar length and width) differ
      between fish that have been pre-acclimated to different temperatures. This study
      shows that a thermal change affects gill plasticity affecting whole-organism ion
      balance two weeks after salinity transfer.

PMID- 29056478
TI  - Survival of pathogenic Mycobacterium abscessus subsp. massiliense in Acanthamoeba
      castellanii.
AB  - We used an amoeba model to study the intracellular growth and cytotoxicity of
      clinical strains of Mycobacterium abscessus subsp. massiliense (Mabsm) isolated
      from 2 patients (one with cystic fibrosis, the other one with idiopathic
      bronchiectasis) during the early (smooth colonies) and late stage (rough
      colonies) of chronic pulmonary infection. Acanthamoeba castellanii were infected
      with Mabsm (MOI 100) and samples collected every 24 h for 72 h. Results showed
      Mabsm is able to survive in trophozoites and persist in cysts for at least 7
      days. Late Mabsm demonstrated higher cytotoxicity toward A. castellanii when
      compared to early strains. A. castellanii is a useful in vitro host model to
      study infection of Mabsm clinical isolates.

PMID- 29056480
TI  - The hatching process and mechanisms of adaptive hatching acceleration in
      hourglass treefrogs, Dendropsophus ebraccatus.
AB  - Environmentally cued hatching is well documented in anurans, enabling embryos to
      escape diverse threats. However, knowledge of anuran hatching mechanisms is
      limited and based largely on aquatic-breeding species without known plasticity in
      hatching timing. Generally, hatching gland cells produce a hatching enzyme that
      degrades the vitelline membrane. We investigated hatching and its regulation in
      terrestrial embryos of hourglass treefrogs, Dendropsophus ebraccatus, which
      accelerate hatching to escape dehydration. We specifically tested if changes in
      hatching gland cell development or hatching enzyme gene expression are associated
      with accelerated hatching. We measured perivitelline chamber size of well
      hydrated eggs over development as an indicator of breakdown of the vitelline
      membrane and found that the size of the perivitelline chamber increased steadily
      until hatching, suggesting gradual hatching enzyme release and vitelline membrane
      degradation. Hatching gland cells peaked in abundance and began regression
      substantially prior to hatching, but we found no developmental differences in the
      abundance or surface area of hatching gland cells between dry and well-hydrated
      embryos. Hatching enzyme gene expression also peaked early in development then
      declined, with no difference between hydration treatments. In D. ebraccatus
      breakdown of the vitelline membrane appears gradual, mediated by hatching enzyme
      release starting long before hatching. However, hatching acceleration is not
      associated with ontogenetic changes in hatching gland cell development or
      hatching enzyme gene expression. This hatching process contrasts with that of red
      eyed treefrogs, Agalychnis callidryas, which appear to release enzyme acutely at
      hatching, yet both species are capable of hatching to escape acute threats.

PMID- 29056481
TI  - Targeting the Late Stage of HIV-1 Entry for Antibody-Dependent Cellular
      Cytotoxicity: Structural Basis for Env Epitopes in the C11 Region.
AB  - Antibodies can have an impact on HIV-1 infection in multiple ways, including
      antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection
      observed in the RV144 vaccine trial. One of the most potent ADCC-inducing
      epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the
      crystal structure, at 2.9 A resolution, of the C11-like antibody N12-i3, in a
      quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an
      A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N
      terminal "eighth strand" of a critical beta sandwich, which our analysis
      indicates to be emblematic of a late-entry state, after the gp120 detachment. In
      prior entry states, this sandwich comprises only seven strands, with the eighth
      strand instead pairing with a portion of the gp120 C terminus. The conformational
      gymnastics of HIV-1 gp120 thus includes altered beta-strand pairing, possibly to
      reduce immunogenicity, although nevertheless still recognized by the human immune
      system.

PMID- 29056482
TI  - Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41
      Protein.
AB  - The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an
      unknown structure. It plays important roles in HIV-1 replication such as
      mediating envelope (Env) intracellular trafficking and incorporation into
      assembling virions, mechanisms of which are poorly understood. Here, we present
      the solution structure of gp41CT in a micellar environment and characterize its
      interaction with the membrane. We show that the N-terminal 45 residues are
      unstructured and not associated with the membrane. However, the C-terminal 105
      residues form three membrane-bound amphipathic alpha helices with distinctive
      structural features such as variable degree of membrane penetration, hydrophobic
      and basic surfaces, clusters of aromatic residues, and a network of cation-pi
      interactions. This work fills a major gap by providing the structure of the last
      segment of HIV-1 Env, which will provide insights into the mechanisms of Gag
      mediated Env incorporation as well as the overall Env mobility and conformation
      on the virion surface.

PMID- 29056484
TI  - A new scale measuring translation of the humeral head as a prognostic factor for
      the treatment of large and massive rotator cuff tears.
AB  - BACKGROUND: Failure rates after rotator cuff repair remain high in patients with
      massive tears. Although superior translation of the humeral head has been used to
      assess the severity of rotator cuff tears, the relevance of anterior migration of
      the humeral head to clinical outcomes has not been established. The purpose of
      this study was to investigate the potential role of the T-scale, a measure of the
      anterolateral translation of the humeral head, as a prognostic factor for rotator
      cuff repair. METHODS: One hundred twenty consecutive patients with full-thickness
      rotator cuff tears underwent primary rotator cuff repair. The T-scale and
      acromiohumeral interval (AHI) were measured preoperatively on axial computed
      tomography scans and radiographs, respectively. The correlations of the T-scale
      and AHI with previously published scores and active forward elevation (FE) were
      investigated. The outcome of rotator cuff repairs was compared between patients
      with positive and patients with negative preoperative T-scale values. RESULTS:
      The preoperative T-scale but not AHI correlated significantly with postoperative
      FE and clinical scores in patients with large to massive tears but not in those
      with small to medium tears. Postoperative FE and clinical scores were
      significantly higher in patients with positive T-scale values than in those with
      negative T-scale values. The relative risk of retear was 2.0 to 7.9 times greater
      in patients with negative T-scale values. CONCLUSION: Patients with large to
      massive tears and negative T-scale values had poorer clinical outcomes and higher
      retear rates. A negative T-scale value represents a useful prognostic factor for
      considering reverse shoulder arthroplasty in patients at greater risk of retear
      after rotator cuff repair.

PMID- 29056483
TI  - Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of
      Glaucoma-Associated Myocilin.
AB  - Glaucoma-associated myocilin is a member of the olfactomedins, a protein family
      involved in neuronal development and human diseases. Molecular studies of the
      myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a Y
      shaped parallel dimer-of-dimers with distinct tetramer and dimer regions. The
      structure of the dimeric C-terminal 7-heptad repeats elucidates an unexpected
      repeat pattern involving inter-strand stabilization by oppositely charged
      residues. Molecular dynamics simulations reveal an alternate accessible
      conformation in which the terminal inter-strand disulfide limits the extent of
      unfolding and results in a kinked configuration. By inference, full-length
      myocilin is also branched, with two pairs of C-terminal olfactomedin domains.
      Selected variants within the N-terminal region alter the apparent quaternary
      structure of myocilin but do so without compromising stability or causing
      aggregation. In addition to increasing our structural knowledge of naturally
      occurring extracellular coiled coils and biomedically important olfactomedins,
      this work broadens the scope of protein misfolding in the pathogenesis of
      myocilin-associated glaucoma.

PMID- 29056485
TI  - Biodegradation of inorganic drug delivery systems in subcutaneous conditions.
AB  - Despite extensive efforts to develop delivery systems for oral administration,
      subcutaneous (s.c.) injection remains the most common way to administer peptide
      drugs. To limit the number of frequent injections, sustained release systems that
      are easy to produce, suitable for various drugs, safe and biodegradable are
      urgently needed. Porous silicon (PSi) has been recognized to be one of the most
      promising materials for s.c. peptide delivery, but its biodegradation in s.c.
      tissue has not been studied in vivo, despite extensive in vitro research. In the
      present study, differently modified PSi microparticles were injected s.c. in
      mice, after which the morphology of the particles was thoroughly studied with
      transmission electron microscopy, micro-computed tomography and X-ray
      diffraction. Furthermore, histopathology of the s.c. tissue was analyzed to
      evaluate biocompatibility. To the best of our knowledge, this is the first
      systematic study which reveals the degradation behavior of various PSi materials
      in vivo. The PSi surface chemistry significantly affected the biodegradation rate
      of the s.c. injected microparticles. The most hydrophobic PSi microparticles with
      hydrocarbonized surface showed the lowest biodegradation rate while the
      hydrophilic microparticles, with oxide surface, degraded the fastest. The results
      from different empirical methods complemented each other to deduce the
      biodegradation mechanism of the inorganic delivery system, providing useful
      information for future development of s.c. carriers.

PMID- 29056486
TI  - Angiographic assessment of atherosclerotic load at the lower extremity in
      patients with diabetic foot and charcot neuro-arthropathy.
AB  - BACKGROUND: The aim of this study was to investigate atherosclerotic load at the
      lower extremity in patients with diabetic foot and charcot neuro-arthropathy and
      compare them with patients with diabetic foot without charcot neuro-arthropathy.
      METHODS: This retrospective study consists of 78 patients with diabetic foot who
      had lower extremity angiography with antegrade approach. All patients were
      classified into two groups; neuro ischemic wounds with charcot neuro-arthropathy
      (30/78) and without charcot neuro-arthropathy (48/78).Atherosclerotic load at the
      side of diabetic foot was determined by using the Bollinger angiogram scoring
      method. Comparison of atherosclerotic load between the two groups was performed.
      RESULTS: The mean of total and infrapopliteal level angiogram scoring of all
      patients was 33.3 (standard deviation, sd:+/-17.2) and 29.3 (sd:+/-15.6),
      respectively. The mean of total and infrapopliteal level angiogram scoring of
      neuroischemic wounds with charcot neuro-arthropathy group was 18.1 (sd:+/-11.6)
      and 15.7 (sd:+/-10.4), respectively. The mean of total and infrapopliteal level
      angiogram scoring of neuroischemic wounds without charcot neuro-arthropathy group
      was 42.8 (sd:+/-12.7) and 37.7 (sd:+/-12.0), respectively. There was a
      statistically significant difference between the two groups of mean total and
      infrapopliteal angiogram scoring (p < 0.01). CONCLUSION: This angiographic study
      confirms that the atherosclerotic load in patients with diabetic foot and chronic
      charcot neuro-arthropathy is significantly less than in patients with
      neuroischemic diabetic foot wounds without chronic charcot neuro-arthropathy.

PMID- 29056487
TI  - Transcriptome profiling of red swamp crayfish (Procambarus clarkii)
      hepatopancreas in response to lipopolysaccharide (LPS) infection.
AB  - The RNA-sequencing followed by de novo assembly generated 61,912 unigene
      sequences of P. clarkii hepatopancreas. Comparison of gene expression between LPS
      challenged and PBS control samples revealed 2552 differentially expressed genes
      (DEGs). Of these sequences, 1162 DEGs were differentially up-regulated and 1360
      DEGs differentially down-regulated. The DEGs were then annotated against gene
      ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG)
      database. Some immune-related pathways such as PPAR signaling pathway, lysosome,
      Chemical carcinogenesis, Peroxisome were predicted by canonical pathways
      analysis. The reliability of transcriptome data was validated by quantitative
      real time polymerase chain reaction (qRT-PCR) for the selected genes. The data
      presented here shed light into antibacterial immune responses of crayfish. In
      addition, these results suggest that transcriptomic data provides valuable
      sequence resource for immune-related gene identification and helps to understand
      P. clarkii immune functions.

PMID- 29056488
TI  - Lack of in vivo cross-protection of two different betanodavirus species RGNNV and
      SJNNV in European sea bass Dicentrachus labrax.
AB  - Viral encephalopathy and retinopathy (VER) is a severe infective disease
      characterized by neuropathological changes in several fish species associated
      with high mortality. The etiological agent is a virus belonging to the
      Nodaviridae family, genus Betanodavirus. To date, four different betanodavirus
      species have been officially recognized by International Committee on Taxonomy of
      Viruses (ICTV), namely the red-spotted grouper- (RGNNV), the striped jack-
      (SJNNV), the barfin flounder- (BFNNV) and the tiger puffer nervous necrosis virus
      (TPNNV). Moreover, two reassortants RGNNV/SJNNV and SJNNV/RGNNV have been
      described. Betanodaviruses can be classified into three different serotypes (A, B
      and C) that are antigenically different, so none (between serotype A and C) or
      partial (between serotype B and C) cross-immunoreactivity has been detected in
      vitro. In this study we investigated the in vivo cross-protection of the two main
      betanodavirus species (RGNNV and SJNNV), which belong to distinct serotype, by
      immunizing intraperitoneally (IP) juvenile sea bass with formalin inactivated
      RGNNV and SJNNV vaccines, followed by a challenge with RGNNV. Fish IP vaccinated
      with inactivated RGNNV showed a high protection value (85%). Serological analyses
      highlighted a great specific anti-NNV immunoglobulin M (IgM) production against
      the homologous virus, while a good seroconversion with low neutralization
      property was highlighted against the heterologous virus. In fish IP vaccinated
      with inactivated SJNNV the protection recorded was equal to 25%, significantly
      lower respect to the one provided by RGNNV IP vaccine. ELISA test detected good
      IgM production against the homologous virus, and a lower, but still detectable
      IgM production against the heterologous one. By contrast, serum neutralization
      test highlighted a poorly detectable antibody production unable to neutralize
      either the homologous or the heterologous virus. These results confirm that the
      two serotypes are not cross-protective in vivo. According to these findings, the
      production of multivalent formulation, or at least the provision of different
      types of vaccines based on both fish and virus species requirement, should be
      recommended in order to broaden the range of protection.

PMID- 29056489
TI  - Laboratory simulation reveals significant impacts of ocean acidification on
      microbial community composition and host-pathogen interactions between the blood
      clam and Vibrio harveyi.
AB  - It has been suggested that climate change may promote the outbreaks of diseases
      in the sea through altering the host susceptibility, the pathogen virulence, and
      the host-pathogen interaction. However, the impacts of ocean acidification (OA)
      on the pathogen components of bacterial community and the host-pathogen
      interaction of marine bivalves are still poorly understood. Therefore, 16S rRNA
      high-throughput sequencing and host-pathogen interaction analysis between blood
      clam (Tegillarca granosa) and Vibrio harveyi were conducted in the present study
      to gain a better understanding of the ecological impacts of ocean acidification.
      The results obtained revealed a significant impact of ocean acidification on the
      composition of microbial community at laboratory scale. Notably, the abundance of
      Vibrio, a major group of pathogens to many marine organisms, was significantly
      increased under ocean acidification condition. In addition, the survival rate and
      haemolytic activity of V. harveyi were significantly higher in the presence of
      haemolymph of OA treated T. granosa, indicating a compromised immunity of the
      clam and enhanced virulence of V. harveyi under future ocean acidification
      scenarios. Conclusively, the results obtained in this study suggest that future
      ocean acidification may increase the risk of Vibrio pathogen infection for marine
      bivalve species, such as blood clams.

PMID- 29056490
TI  - Nucleus positioning within Drosophila egg chamber.
AB  - Both types of Drosophila egg chamber germ cells, i.e. oocyte and nurse cells,
      have to control their nucleus positions in order to produce a viable gamete.
      Interestingly, while actin microfilaments are crucial to position the nuclei in
      nurse cells, these are the microtubules that are important for oocyte nucleus to
      migrate and adopt the correct position. In this review, we discuss the mechanisms
      underlying these positioning processes in the two cell types with respect to the
      organization and dynamics of the actin and microtubule skeleton. In the nurse
      cells it is essential to keep firmly the nuclei in a central position to prevent
      them from obstructing the ring canals when the cytoplasmic content of the cells
      is dumped into the oocyte cells toward the end of oogenesis. This is achieved by
      the assembly of thick filopodia-like actin cables anchored to the plasma
      membrane, which grow inwardly and eventually encase tightly the nuclei in a cage
      like structure. In the oocyte, the migration at an early stage of oogenesis of
      the nucleus from a posterior location to an anchorage site at an asymmetric
      anterior position, is an essential step in the setting up of the dorsoventral
      polarity axis of the future embryo. This process is controlled by an interplay
      between MT networks that just start to be untangled. Although both mechanisms
      have evolved to fulfill cell-type specific cell processes in the context of fly
      oogenesis, interesting parallels can be drawn with other nuclear positioning
      mechanisms in the mouse oocyte and the developing muscle respectively.

PMID- 29056491
TI  - Dimensional symptom severity and global cognitive function predict subjective
      quality of life in patients with schizophrenia and healthy adults.
AB  - Over the last several decades Quality of Life (QoL) has become increasingly
      important as an indicator of treatment outcomes; particularly in schizophrenia
      spectrum disorders because of its close association with functional disability.
      Numerous studies seeking to elucidate the factors that contribute to QoL in this
      population have implicated both symptom severity and cognition in determining QoL
      but the findings have been mixed. The critical factors that appear to impede the
      lack of consensus in the extant literature examining determinants of QoL include
      the heterogeneity of the samples and measures examined as well as medication
      effects across different studies. Thus, the present study sought to address some
      of these issues by examining the relationship between subjective QoL and both
      symptom severity and cognitive function in a relatively homogeneous patient
      sample of patients and a community control sample assessed for dimensional
      symptom severity. Our results suggest that both global cognitive function and
      psychiatric symptoms have a significant impact on the subjective QoL of both
      people with schizophrenia spectrum disorders and psychiatrically healthy adults.
      Specifically, we found that a global index of cognition as well as self-reported
      avolitional and depressive symptoms were significantly predictive of QoL in both
      samples. These findings highlight the importance of addressing cognitive,
      depressive and avolitional symptoms in the treatment of patients with
      schizophrenia spectrum disorders and suggest that improvements in these domains
      may have a meaningful impact on their overall QoL.

PMID- 29056492
TI  - Prevalence, risk factors and clinical characteristics of osteoporosis in Chinese
      inpatients with schizophrenia.
AB  - Patients with schizophrenia have a high prevalence of developing osteoporosis and
      osteoporosis-related fractures. We examined the prevalence of osteoporosis and
      its clinical correlates in Chinese patients with schizophrenia, which is not well
      studied. A total of 199 inpatients (males/females=132/67; average age: 54.5+/
      11.1years) and 107 healthy controls (males/females=22/85; average age: 41.7+/
      11.9years) were recruited. Bone mineral density (BMD) was measured by
      ultrasonography of the calcaneus. The prevalence of osteoporosis and low BMD
      (osteoporosis and osteopenia) was 23.1% and 65.3% for the patient group, versus
      7.5% and 39.3% for the control group (both p<0.001). Further, the average BMD T
      score in patients was significantly lower than in controls (p<0.05). There was
      gender difference in the prevalence of low BMD conditions for the patients
      (males: 56.1% versus females: 76.1%; p<0.01) as well as the BMD T-score
      (p<0.001). Several risk factors correlated with the osteoporosis classification
      in the patient group: older age (58.9+/-11.2years vs. 53.3+/-11.0years), lower
      weight (63.7+/-12.2kg vs. 70.4+/-15.2kg) and body mass index (BMI) (22.8+/
      4.1kg/m2 vs. 24.2+/-4.7kg/m2; all p<0.01) than those without osteoporosis.
      Stepwise multiple logistic regression analysis indicated that age, weight and BMI
      remained significantly associated with osteoporosis. In addition, correlation
      analysis showed significant correlations between BMD T-score and the following
      parameters: gender, age and drug type (clozapine versus non-clozapine)
      (Bonferroni corrected p's<0.05). Our results suggest a higher prevalence of
      osteoporosis and osteopenia in Chinese schizophrenic inpatients, with both the
      expected risk factors of gender and age, as well as drug type.

PMID- 29056494
TI  - Clustered interventions to reduce inappropriate duplicate laboratory tests in an
      Irish tertiary hospital.
AB  - BACKGROUND: There is increasing emphasis on understanding the rate, and avoidable
      costs, of inappropriate laboratory testing in hospitals, especially associated
      with duplication of tests following transfer of patients from one hospital to
      another. While studies of inappropriate testing have been reported previously,
      there are no published data relevant to Ireland. AIMS: To determine the baseline
      rate of inappropriate testing for a subset of clinical parameters, specifically,
      full blood counts (FBC), biochemistry profiles (Bio) and coagulation (Coag)
      screens for geriatric patients transferring to and from University Hospital
      Limerick (UHL). Prospective pilot-scale implementation of five clustered
      interventions, and assessment of their effect. METHODS: Baseline testing levels
      were determined between October 2013 and January 2014. A patient survey was
      conducted to evaluate patient awareness of the blood tests they underwent. Five
      interventions were trialed sequentially each month between January and May 2014.
      These included: educational poster, intern training, presentations and
      communication to consultants; automated prompt in the Lab Information Technology
      system; highlighting of patient survey results to medical staff; inclusion of
      laboratory test details on patient transfer document; patient booklet promoting
      empowerment. Impact was assessed by determining rates of inappropriate laboratory
      testing monthly, and associated actual cost reductions were calculated. RESULTS:
      Approximately two-thirds of geriatric inpatients were unaware of why they
      underwent blood tests. Baseline numbers of inappropriate duplicate FBCs, Bio
      profiles and Coag tests were 758, 749 and 268 respectively for patients
      transferring to and from UHL. Following the interventions, these numbers dropped
      to 85, 84 and 0, respectively. CONCLUSION: The interventions resulted in
      sustained reduction in rates of inappropriate testing by May 2014. Extrapolated
      cost reductions exceed two million Euro annually. The most effective intervention
      involved staff education.

PMID- 29056493
TI  - Genetic analysis of deep phenotyping projects in common disorders.
AB  - Several studies of complex psychotic disorders with large numbers of
      neurobiological phenotypes are currently under way, in living patients and
      controls, and on assemblies of brain specimens. Genetic analyses of such data
      typically present challenges, because of the choice of underlying hypotheses on
      genetic architecture of the studied disorders and phenotypes, large numbers of
      phenotypes, the appropriate multiple testing corrections, limited numbers of
      subjects, imputations required on missing phenotypes and genotypes, and the cross
      disciplinary nature of the phenotype measures. Advances in genotype and phenotype
      imputation, and in genome-wide association (GWAS) methods, are useful in dealing
      with these challenges. As compared with the more traditional single-trait
      analyses, deep phenotyping with simultaneous genome-wide analyses serves as a
      discovery tool for previously unsuspected relationships of phenotypic traits with
      each other, and with specific molecular involvements.

PMID- 29056495
TI  - Synthesis of nano-cuboidal gold particles for effective antimicrobial property
      against clinical human pathogens.
AB  - Algae could offer a potential source of fine chemicals, pharmaceuticals and
      biofuels. In this study, a green synthesis of dispersed cuboidal gold
      nanoparticles (AuNPs) was achieved using red algae, Gelidium amansii reacted with
      HAuCl4. It was found to be 4-7 nm sized cubical nanoparticles with aspect ratio
      of 1.4 were synthesized using 0.5 mM of HAuCl4 by HRSEM analysis. The crystalline
      planes (111), (200), (220), (311) and elemental signal of gold was observed by
      XRD and EDS respectively. The major constitutes, galactose and 3,6
      anhydrogalactose in the alga played a critical role in the synthesis of
      crystalline AuNPs with cubical dimension. Further, the antibacterial potential of
      synthesized AuNPs was tested against human pathogens, Escherichia coli and
      Staphylococcus aureus. The synthesized AuNPs found biocompatible up to 100 ppm
      and high concentration showed an inhibition against cancer cell. This novel
      report could be helped to exploration of bioresources to material synthesis for
      the application of biosensor and biomedical application.

PMID- 29056496
TI  - The spread of Vibrio parahaemolyticus in tissues of the Pacific white shrimp
      Litopenaeus vannamei analyzed by PCR and histopathology.
AB  - V. parahaemolyticus are bacteria that cause the Acute Hepatopancreatic Necrosis
      Disease (AHPND), or Early Mortality Syndrome (EMS), in shrimp. To further
      understand the pathogenesis mechanisms of V. parahaemolyticus infection in
      shrimp, the spreading of this bacterium in various tissues was investigated. The
      spread of infection in shrimp that were exposed to seawater bacteria was studied
      by PCR and histopathology at 1 min, 1, 6, 12, 24, 48 and 72 h after exposure. The
      PCR results showed that V. parahaemolyticus was at its most widespread at 6 h
      after exposure, at which point V. parahaemolyticus was found in the gills,
      hepatopancreas, intestine, muscles, and hemolymph. However, examinations after 6
      h of infection found only small amounts of V. parahaemolyticus in hepatopancreas
      and intestines. Histopathology of the hepatopancreas showed abnormalities on
      gross examination at 1 min-72 h after exposure. This study indicates that V.
      parahaemolyticus can spread quickly by using the hepatopancreas as the target
      tissue. After 6 h of infection, V. parahaemolyticus was eliminated by immune
      system while their toxins still caused damage to shrimp tissues.

PMID- 29056497
TI  - Rhein induces apoptosis and autophagy in human and rat glioma cells and mediates
      cell differentiation by ERK inhibition.
AB  - In this study, we investigated the anticancer potentials of Rhein, an
      anthraquinone derivative of most commonly used Chinese rhubarb on the rat F98
      glioma cells. The experimental studies revealed that Rhein induced cell cycle
      arrest, caspase mediated apoptosis. It results in the formation of intracellular
      acidic vesicles in cytoplasm, leading to autophagy. Differentiation of viable
      cells towards elongation of matured astrocytes was proved by monitoring dramatic
      changes in morphological characteristics as well as identified from the elevation
      of glial fibrillary acidic protein (GFAP) expression. Rhein treatment did not
      alter the phosphorylated MAPKs activation including p-38, JNK and NF-kappaB,
      transcription unit whereas rhein significantly inhibited ERK1/2 activation in F98
      glioma cells. PD98059, a specific inhibitor for ERK activation imitates rhein
      effects on morphology and expressions of GFAP but did not help to induce any
      apoptosis or autophagy. Collective data exhibited that potentials of rhein in
      anti-cancer property in ERK-independent apoptosis and autophagy in association
      with downregulated ERK-dependent differentiation process of glioma cell lines.

PMID- 29056498
TI  - A Comparison of 3 Videolaryngoscopes for Double-Lumen Tube Intubation in Humans
      by Users With Mixed Experience: A Randomized Controlled Study.
AB  - OBJECTIVES: To test the hypothesis that laryngoscopy using the Airtraq (Prodol
      Limited, Viscaya, Spain) or King Vision laryngoscope (KVL) (Ambu A/S, Ballerup,
      Denmark) would result in a shorter time for successful double-lumen endobronchial
      tube (DLT) intubation by users with mixed experience than the time required using
      the Macintosh or GlideScope (Verathon Inc., Bothell, WA) laryngoscopes. DESIGN: A
      randomized, prospective, blind study. SETTING: A single university hospital.
      PARTICIPANTS: The study comprised 133 patients undergoing elective thoracic
      surgery. INTERVENTIONS: Patients were randomly allocated into the following 4
      groups of DLTs: Macintosh (n = 32), GlideScope (n = 34), Airtraq (n = 35), or KVL
      (n = 32). MEASUREMENTS AND MAIN RESULTS: The following data were recorded: time
      required for achieving successful DLT intubation; glottis visualization;
      optimization maneuvers; first-pass success rate; intubation difficulty; failure
      to intubate, defined as an attempt taking >150 seconds to perform or if
      peripheral oxygen saturation <92% was noted; and postoperative sore throat and
      hoarseness were recorded. Compared with GlideScope, the Airtraq resulted in
      shorter times for achieving successful DLT intubation (median times: 21 s [95%
      confidence interval 23.9-70.8 s] v 57.5 s [95% confidence interval 46.2-89.1 s],
      respectively; p = 0.021); a lower score for difficult intubations (p = 0.023);
      and fewer optimization maneuvers. The 4 laryngoscopes were associated with
      comparable glottis visualization; first-pass success rate (100%, 100%, 94.4%, and
      100%, respectively; p = 0.522); incidence of oropharyngeal trauma; postoperative
      sore throat; and hoarseness of voice. There were 2 (5.7%) endobronchial
      intubation failures using the Airtraq due to the inability to advance the DLT
      through the glottis opening. The experience of the anesthesiologists in using the
      4 devices had a statistically significant negative correlation with the time to
      confirmation of endobronchial intubation (Spearman r -0.392; p < 0.001).
      CONCLUSION: When used by operators with mixed experience, the channeled Airtraq
      required less time for DLT intubation and was easier to use than the GlideScope,
      although failures did occur with the Airtraq, whereas they did not occur with the
      other systems.

PMID- 29056499
TI  - The allosteric site regulates the voltage sensitivity of muscarinic receptors.
AB  - Muscarinic receptors (M-Rs) for acetylcholine (ACh) belong to the class A of G
      protein-coupled receptors. M-Rs are activated by orthosteric agonists that bind
      to a specific site buried in the M-R transmembrane helix bundle. In the active
      conformation, receptor function can be modulated either by allosteric modulators,
      which bind to the extracellular receptor surface or by the membrane potential via
      an unknown mechanism. Here, we compared the modulation of M1-Rs and M3-Rs induced
      by changes in voltage to their allosteric modulation by chemical compounds. We
      quantified changes in receptor signaling in single HEK 293 cells with a FRET
      biosensor for the Gq protein cycle. In the presence of ACh, M1-R signaling was
      potentiated by voltage, similarly to positive allosteric modulation by benzyl
      quinolone carboxylic acid. Conversely, signaling of M3-R was attenuated by
      voltage or the negative allosteric modulator gallamine. Because the orthosteric
      site is highly conserved among M-Rs, but allosteric sites vary, we constructed
      "allosteric site" M3/M1-R chimeras and analyzed their voltage dependencies.
      Exchanging the entire allosteric sites eliminated the voltage sensitivity of ACh
      responses for both receptors, but did not affect their modulation by allosteric
      compounds. Furthermore, a point mutation in M3-Rs caused functional uncoupling of
      the allosteric and orthosteric sites and abolished voltage dependence. Molecular
      dynamics simulations of the receptor variants indicated a subtype-specific
      crosstalk between both sites, involving the conserved tyrosine lid structure of
      the orthosteric site. This molecular crosstalk leads to receptor subtype-specific
      voltage effects.

PMID- 29056500
TI  - Emerging role of non-coding RNA in oral cancer.
AB  - Oral squamous cell carcinoma (OSCC) is characterized by genomic and epigenomic
      alterations. However, the mechanisms underlying oral squamous cell carcinoma
      tumorigenesis and progression remain to be elucidated. Long non-coding RNAs
      (lncRNAs), circular RNAs (circRNAs), and extracellular RNAs (exRNAs) are emerging
      groups of regulatory RNAs, which possess low or no protein-coding potential.
      Emerging lines of evidence indicates that deregulated expression of lncRNAs and
      circular RNAs are associated with the induction and progression of various
      cancers, including oral cancer, through epigenetic, transcriptional, and post
      transcriptional alterations. In this review, we highlight the expression and
      functional roles of extracellular RNAs, lncRNAs, and circular RNAs in oral
      squamous cell carcinoma and discuss their potential clinical applications as
      diagnostic or prognostic biomarkers, and therapeutic targets.

PMID- 29056501
TI  - MY APPROACH to the pregnant patient with a supraventricular tachycardia*.

PMID- 29056502
TI  - Factors Associated With Post-Stroke Physical Activity: A Systematic Review and
      Meta-Analysis.
AB  - OBJECTIVE: To integrate the literature investigating factors associated with post
      stroke physical activity. DATA SOURCES: A search was conducted from database
      inception to June 2016 across 9 databases: Cochrane, MEDLINE, ProQuest, Web of
      Science, PsycINFO, Scopus, Embase, CINAHL, and Allied and Complementary Medicine
      Database. The reference lists of included articles were screened for secondary
      literature. STUDY SELECTION: Cohort and cross-sectional studies were included if
      they recruited community-dwelling stroke survivors and measured factors
      associated with physical activity. DATA EXTRACTION: Risk of bias was evaluated
      using the Quality in Prognosis Studies checklist. A meta-analysis was conducted
      for correlates where there were at least 2 studies that reported a correlation
      value. Correlation values were used in an effect size measure and converted to a
      standardized unit with Fisher r to z transformation and conversion back to r
      method. Results were described qualitatively for studies that could not be
      pooled. DATA SYNTHESIS: There were 2161 studies screened and 26 studies included.
      Age (meta r=-.17; P<=.001) and sex (meta r=-.01; P=.02) were the nonmodifiable
      factors that were found to be associated with post-stroke physical activity. The
      modifiable factors were physical function (meta r=.68-.73; P<.001),
      cardiorespiratory fitness (meta r=.35; P<=.001), fatigue (meta r=-.22; P=.01),
      falls self-efficacy (meta r=-.33; P<.001), balance self-efficacy (meta r=.37;
      P<.001), depression (meta r=-.58 to .48; P<.001), and health-related quality of
      life (meta r=.38-.43; P<.001). The effect of side of infarct, neglect, and
      cognition on post-stroke physical activity was inconclusive. CONCLUSIONS: Age,
      sex, physical function, depression, fatigue, self-efficacy, and quality of life
      were factors associated with post-stroke physical activity. The cause and effect
      of these relations are unclear, and the possibility of reverse causality needs to
      be addressed.

PMID- 29056504
TI  - Superior oblique myokymia.
AB  - Superior oblique myokymia (SOM) is a rare condition of unclear etiology. We
      discuss the history, etiology, clinical features, differential diagnoses,
      management, and prognosis of SOM. We conducted a meta-analysis of all 116 cases
      published since SOM was first described in 1906. The age at examination was 17-72
      years (mean: 42 years.) There was a right-sided preponderance in 61% of cases (P
      < 0.02) that was statistically significant in females (63%, P < 0.04) but not in
      males (59%, P = 0.18). The pathophysiology of SOM may be neurovascular
      compression and/or ephaptic transmission. Although various pharmacological and
      surgical approaches to SOM treatment have been proposed, the rarity of the
      condition has made it impossible to conduct clinical trials evaluating the safety
      and efficacy of these approaches. Recently, topical beta blockers have managed
      SOM symptoms in a number of cases, including the first case treated with
      levobunolol. Systemic medications, strabismus surgery, and neurosurgery have been
      used to control symptoms, with strabismus surgery carrying a moderate risk of
      postoperative diplopia in downgaze. Although there is no established treatment
      for SOM, we encourage clinicians to attempt topical levobunolol therapy before
      considering systemic therapy or surgery.

PMID- 29056503
TI  - Charles Dickens, trachoma, and blindness in pre-Victorian England.
AB  - In the early 1820s, a Yorkshire boarding school was devastated by an outbreak of
      blinding ophthalmia. The cause of the epidemic was-in all likelihood-trachoma,
      then known as Egyptian ophthalmia. The headmaster of the Yorkshire school,
      William Shaw, was sued for gross negligence by 2 families whose sons went blind
      during the outbreak. The epidemic and trial would play a role in creating one of
      the literature's most notorious fictional characters. Eighteen years after the
      trial, Charles Dickens modeled the vile schoolmaster Wackford Squeers in Nicholas
      Nickleby after Shaw, whose reputation and career would later be ruined by his
      thinly disguised portrayal in the novel. The original boarding school epidemic
      took place while London's first eye hospital was moving to Lower Moorfields, an
      institution that 17 years earlier was established primarily to cope with Egyptian
      ophthalmia. We explore trachoma's wide-ranging impact on pre-Victorian England,
      from inspiring an enduring literary villain to the creation of a renowned eye
      hospital.

PMID- 29056505
TI  - Ly6Chi monocytes are required for mesenchymal stem/stromal cell-induced immune
      tolerance in mice with experimental autoimmune uveitis.
AB  - The cells of the innate immune system, in addition to their capacity to elicit
      immunity, play a substantial role in immune tolerance induction. Our group has
      recently shown that a distinct subset of MHC IIhiB220hiCD11bmid suppressive
      macrophages is increased in the lung by intravenous (IV) administration of
      mesenchymal stem/stromal cells (MSC) and induces immune tolerance. Herein, we
      demonstrate that circulating CD11bhiLy6Chi monocytes are precursors to MHC
      IIhiB220hiCD11bmid macrophages in the lung and required for MSC-induced tolerance
      in a mouse model of experimental autoimmune uveitis (EAU). Analysis revealed that
      IV MSC induced an increase in IL-10-expressing MHC IIhiB220hiCD11bmid macrophages
      in the lung with a concomitant decrease in CD11bhiLy6Chi monocytes. Selective
      depletion of circulating CD11bhiLy6Chi cells abrogated the effects of MSC in the
      induction of IL-10hiMHC IIhiB220hiCD11bmid macrophages and immune tolerance in
      EAU mice. Similarly, an increase in CD4+CD25+Foxp3+ Tregs by MSCs was also
      reversed by CD11bhiLy6Chi cell depletion. These results suggest that
      CD11bhiLy6Chi monocytes are critical for MSC-induced immune tolerance.

PMID- 29056506
TI  - The zinc form of carnosine dipeptidase 2 (CN2) has dipeptidase activity but its
      substrate specificity is different from that of the manganese form.
AB  - Carnosine dipeptidase II (CN2), a metallopeptidase present in the cytosol of
      various vertebrate tissues, catalyzes the hydrolysis of carnosine and several
      other dipeptides in the presence of Mn2+. Although the metal-binding center of
      mouse CN2 is also able to associate with Zn2+in vitro, it was not known whether
      the zinc form of CN2 has any enzymatic activity. In the present study, we show
      that Zn2+ has a higher affinity for binding to CN2 than Mn2+, as evidenced by
      native mass spectrometry. The issue of whether the zinc form of CN2 has enzymatic
      activity was also examined using various dipeptides as substrates. The findings
      indicate that the zinc form of CN2 catalyzes the hydrolysis of several different
      dipeptides including Leu-His, Met-His and Ala-His at a reaction rate comparable
      to that for its manganese form. On the other hand, the zinc form of CN2 did not
      catalyze the hydrolysis of carnosine and several other dipeptides that are
      hydrolyzed by the manganese form of CN2. Substrate specificity was also examined
      in HEK293T cells expressing CN2, and the findings indicate that Leu-His, Met-His,
      but not carnosine, were hydrolyzed in the cell culture. These results suggest
      that the zinc form of CN2 is an active enzyme, but with a different substrate
      specificity from that of the manganese form.

PMID- 29056507
TI  - MeWRKY20 and its interacting and activating autophagy-related protein 8 (MeATG8)
      regulate plant disease resistance in cassava.
AB  - As a highly conserved mechanism, autophagy is responsible for the transport of
      cytoplasmic constituents in the vacuoles or lysosomes. Moreover, autophagy is
      essential for plant development and various stress responses. In this study, 34
      MeATGs were systematically identified in cassava, and their transcripts were
      commonly regulated by Xanthomonas axonopodis pv manihotis (Xam). Through
      transient expression in Nicotiana benthamiana, the subcellular locations of 4
      MeATG8s were revealed. Notably, MeWRKY20 was identified as physical interacting
      protein of MeATG8a/8f/8h and upstream transcriptional activator of MeATG8a.
      Through virus-induced gene silencing (VIGS) in cassava, we found that MeATG8
      silenced and MeWRKY20-silenced plants resulted in disease sensitive, with less
      callose depositions and lower autophagic activity. This study may facilitate our
      understanding of the upstream MeWRKY20 and underlying target as well as
      interacting proteins of MeATG8s in immune response. Taken together, MeWRKY20 and
      MeATG8a/8f/8h are essential for disease resistance against bacterial blight by
      forming various transcriptional modules and interacting complex in cassava.

PMID- 29056509
TI  - The effect of l-Arginine on Ciliary Beat Frequency in PCD patients, non-PCD
      respiratory patients and healthy controls.
AB  - OBJECTIVES: Few studies have examined the potentially therapeutic effect of
      increasing the production of endogenous nitric oxide (NO) in Primary Ciliary
      Dyskinesia (PCD) and other chronic respiratory conditions. Nasal NO is low in PCD
      and has been found to correlate with compromised Ciliary Beat Frequency (CBF). In
      this study we assessed the effect of increasing l-Arginine, as the substrate of
      NO synthases, on CBF in biopsies of human respiratory ciliated epithelium.
      METHODOLOGY: A total of 28 suspect cases with chronic respiratory manifestations
      referred for PCD diagnostic testing and 8 healthy controls underwent nasal
      brushing. Obtained epithelial cells were divided between three culture medium 199
      solutions, containing different levels of l-Arginine (0.33 mM as baseline, 1 mM
      and 10 Mm as increased levels). CBF measurements were obtained at 37  degrees C
      and 25  degrees C at 1, 3 and 24 h after sample acquisition. RESULTS: Among a
      total of 36 recruited subjects, 8 had PCD confirmed (PCD n = 8), 20 had PCD
      excluded (non-PCD n = 20) and 8 were healthy controls (Healthy Controls = 8).
      Among PCD subjects, ciliary motility was characterized by rotational (n = 5) or
      dyskinetic (n = 3) beating. At 37  degrees C, compared to baseline, higher levels
      of l-Arginine resulted in up to 9% CBF increase at 1 h (p = 0.007), up to 9% CBF
      increase at 3 h (p < 0.001) and up to 12% CBF increase at 24 h (p = 0.002).
      Similar although smaller scale increases were recorded at 25  degrees C. The
      effect of l-Arginine was time dependent (interaction p = 0.002) and was similar
      in PCD patients, non-PCD chronic respiratory patients and healthy controls
      (interaction p = 0.800). CONCLUSIONS: l-Arginine increases CBF and merits to be
      evaluated as a potential stimulator of mucociliary clearance in chronic
      respiratory conditions and congenital ciliary disorders with residual motility.
      Larger human studies are needed to confirm these findings.

PMID- 29056508
TI  - Functions of actin-interacting protein 1 (AIP1)/WD repeat protein 1 (WDR1) in
      actin filament dynamics and cytoskeletal regulation.
AB  - Actin-depolymerizing factor (ADF)/cofilin and actin-interacting protein 1 (AIP1),
      also known as WD-repeat protein 1 (WDR1), are conserved among eukaryotes and play
      critical roles in dynamic reorganization of the actin cytoskeleton. AIP1
      preferentially promotes disassembly of ADF/cofilin-decorated actin filaments but
      exhibits minimal effects on bare actin filaments. Therefore, AIP1 has been often
      considered to be an ancillary co-factor of ADF/cofilin that merely boosts
      ADF/cofilin activity level. However, genetic and cell biological studies show
      that AIP1 deficiency often causes lethality or severe abnormalities in multiple
      tissues and organs including muscle, epithelia, and blood, suggesting that AIP1
      is a major regulator of many biological processes that depend on actin dynamics.
      This review summarizes recent progress in studies on the biochemical mechanism of
      actin filament severing by AIP1 and in vivo functions of AIP1 in model organisms
      and human diseases.

PMID- 29056510
TI  - Examination of the pediatric adolescent patient.
AB  - Gynecologic examination of the pediatric adolescent patient provides a valuable
      opportunity for patient education and diagnosis, yet presents special challenges,
      including achieving comfort for the patient and guardian and finding equipment
      that are sized for pediatric patient. Anatomic changes due to the hormonal
      environment evolve from newborn through pubertal development. As pediatric
      adolescent gynecology has evolved as a specialty, techniques and training for
      providing optimal office and surgical examination have emerged. Where possible,
      the patient should be engaged with the examination through use of a mirror or
      positioning. Smaller swabs should be used for testing for vaginal infection in
      prepubertal patients. When speculum or office examination is not possible, use of
      narrow-caliber, flexible, and rigid hysteroscopes allow vaginoscopy for
      assessment.

PMID- 29056511
TI  - CANTOS Ushers in a New Calculus of Inflammasome Targeting for Vascular Protection
      and Maybe More.
AB  - Despite overwhelming basic science linking inflammation to the pathobiology of
      atherothrombosis, the specific clinical evidence indicating cardiovascular
      benefits from anti-inflammatory pharmacotherapy has been lacking. The CANTOS
      trial (Ridker et al., 2017a) now provides the first largescale proof of concept
      that inflammasome targeting can reduce cardiovascular events-and, surprisingly,
      lung cancer.

PMID- 29056512
TI  - Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer
      Metastasis and Recurrence.
AB  - Breast tumor recurrence and metastasis represent the main causes of cancer
      related death in women, and treatments are still lacking. Here, we define the
      lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer
      metastasis. ACC1 phosphorylation was increased in invading cells both in murine
      and human breast cancer, serving as a point of convergence for leptin and
      transforming growth factor (TGF) beta signaling. ACC1 phosphorylation was
      mediated by TGFbeta-activated kinase (TAK) 1, and ACC1 inhibition was
      indispensable for the elevation of cellular acetyl-CoA, the subsequent increase
      in Smad2 transcription factor acetylation and activation, and ultimately
      epithelial-mesenchymal transition and metastasis induction. ACC1 deficiency
      worsened tumor recurrence upon primary tumor resection in mice, and ACC1
      phosphorylation levels correlated with metastatic potential in breast and lung
      cancer patients. Given the demonstrated effectiveness of anti-leptin receptor
      antibody treatment in halting ACC1-dependent tumor invasiveness, our work defines
      a "metabolocentric" approach in metastatic breast cancer therapy.

PMID- 29056513
TI  - Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1
      Sensing Glucoregulatory Pathway.
AB  - The gut microbiota alters energy homeostasis. In parallel, metformin regulates
      upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether
      changes of the microbiota or SGLT1-dependent pathways in the upper small
      intestine mediate metformin action is unknown. Here we report that upper small
      intestinal glucose sensing triggers an SGLT1-dependent pathway to lower glucose
      production in rodents. High-fat diet (HFD) feeding reduces glucose sensing and
      SGLT1 expression in the upper small intestine. Upper small intestinal metformin
      treatment restores SGLT1 expression and glucose sensing while shifting the upper
      small intestinal microbiota partly by increasing the abundance of Lactobacillus.
      Transplantation of upper small intestinal microbiota from metformin-treated HFD
      rats to the upper small intestine of untreated HFD rats also increases the upper
      small intestinal abundance of Lactobacillus and glucose sensing via an
      upregulation of SGLT1 expression. Thus, we demonstrate that metformin alters
      upper small intestinal microbiota and impacts a glucose-SGLT1-sensing
      glucoregulatory pathway.

PMID- 29056514
TI  - Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment.
AB  - The benefits of exercise training for cancer patients are becoming increasingly
      evident. Physical exercise has been shown to reduce cancer incidence and inhibit
      tumor growth. Here we provide the status of the current molecular understanding
      of the effect of exercise on cancer. We propose that exercise has a role in
      controlling cancer progression through a direct effect on tumor-intrinsic
      factors, interplay with whole-body exercise effects, alleviation of cancer
      related adverse events, and improvement of anti-cancer treatment efficacy. These
      findings have wide-ranging societal implications, as this understanding may lead
      to changes in cancer treatment strategies.

PMID- 29056516
TI  - Effect of elevated CO2 concentration and temperature on antioxidant capabilities
      of multiple generations of Bemisia tabaci MEAM1 (Hemiptera: Aleyrodidae).
AB  - A rise in atmospheric carbon dioxide concentration ([CO2]) and a warming climate
      are two of the most conspicuous characteristics of global climate change in this
      century. However, studies addressing the combined impact of rising [CO2] and
      temperature on herbivore insect physiology are still limited. In this study we
      investigated the combined effects of elevated [CO2] and temperature on major
      antioxidative enzymes, including superoxide dismutase (SOD), catalase (CAT),
      peroxidases (POD) and detoxification enzymes of glutathione-S-transferases (GST)
      and acetylcholinesterase (AChE) in three consecutive generations of Bemisia
      tabaci Middle East-Asia Minor 1 (MEAM1, commonly known as B biotype) adults. The
      results indicated that the antioxidant capabilities of B. tabaci differed
      significantly during different treatments across different generations. Elevated
      [CO2] markedly increased POD, GST and AChE activities in the first generation,
      and SOD, CAT and GST activities in the second generation, but reduced POD
      activity in the third generation at ambient temperature. Under elevated
      temperature, elevated [CO2] significantly increased GST and AChE activities in
      the first generation and CAT activity in the third generation, reduced SOD
      activity in the third generation and reduced AChE activity in the second
      generation. [CO2], temperature and insect generation interacted to affect the
      antioxidant capabilities of B. tabaci. These results suggest both that changes in
      antioxidant capabilities vary in response to either [CO2] or temperature, or a
      combination of both, leading to oxidative stress and also that antioxidant
      enzymes play important roles in reducing oxidative damage in B. tabaci. Changes
      in the exposure of antioxidant compounds over the course of three generations
      suggest that acclimation and/or adaptation to elevated [CO2] and temperature may
      have occurred. This study represents the first comprehensive report on the
      antioxidant defense mechanism in successive multiple generations of an insect
      species under combined elevated [CO2] and temperature levels. These results offer
      further insights into the effects of elevated [CO2] and temperature on different
      generations of insect herbivores and provide more detailed information for
      population predictions.

PMID- 29056515
TI  - In Vivo Imaging of Glutamine Metabolism to the Oncometabolite 2-Hydroxyglutarate
      in IDH1/2 Mutant Tumors.
AB  - The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various
      cancers, where it accumulates as a result of mutations in isocitrate
      dehydrogenase (IDH). The metabolic source of 2-HG, in a wide variety of cancers,
      dictates both its generation and also potential therapeutic strategies, but this
      remains difficult to access in vivo. Here, utilizing patient-derived
      chondrosarcoma cells harboring endogenous mutations in IDH1 and IDH2, we report
      that 2-HG can be rapidly generated from glutamine in vitro. Then, using
      hyperpolarized magnetic resonance imaging (HP-MRI), we demonstrate that in vivo
      HP [1-13C] glutamine can be used to non-invasively measure glutamine-derived HP 2
      HG production. This can be readily modulated utilizing a selective IDH1
      inhibitor, opening the door to targeting glutamine-derived 2-HG therapeutically.
      Rapid rates of HP 2-HG generation in vivo further demonstrate that, in a context
      dependent manner, glutamine can be a primary carbon source for 2-HG production in
      mutant IDH tumors.

PMID- 29056517
TI  - Molecular characterization of dengue viruses isolated from patients in Central
      Java, Indonesia.
AB  - BACKGROUND: Dengue is hyper-endemic in Indonesia. Purwokerto city in Central Java
      province is routinely ravaged by the disease. Despite the endemicity of dengue in
      this city, there is still no data on the virological aspects of dengue in the
      city. We conducted a molecular surveillance study of the circulating dengue
      viruses (DENV) in Purwokerto city to gain information on the virus origin,
      serotype and genotype distribution, and phylogenetic characteristics of DENV.
      METHODS: A cross-sectional dengue molecular surveillance study was conducted in
      Purwokerto. Sera were collected from dengue-suspected patients attending three
      hospitals in the city. Diagnosis was performed using dengue NS1 antigen and
      IgG/IgM antibodies detection. DENV serotyping was performed using Simplexa Dengue
      real-time RT-PCR. Sequencing was conducted to obtain full-length DENV Envelope
      (E) gene sequences, which were then used in phylogenetic and genotypic analyses.
      Patients' clinical and demographic data were collected and analyzed. RESULTS: A
      total of 105 dengue-suspected patients' sera were collected, in which 80 (76.2%)
      were positive for IgM and/or IgG, and 57 (54.2%) were confirmed as dengue by NS1
      antigen and/or DENV RNA detection using RT-PCR. Serotyping was successful for 47
      isolates. All four serotypes circulated in the area with DENV-3 as the
      predominant serotype. Phylogenetic analyses grouped the isolates into Genotype I
      for DENV-1, Cosmopolitan genotype for DENV-2, and Genotype I and II for DENV-3
      and -4, respectively. The analyses also revealed the close relatedness of
      Purwokerto isolates to other DENV strains from Indonesia and neighboring
      countries. CONCLUSION: We reveal the molecular and virological characteristics of
      DENV in Purwokerto, Banyumas regency, Central Java. The genotype and phylogenetic
      analyses indicate the endemicity of the circulating DENV in the city. Our
      serotype and genotype data provide references for future dengue molecular
      epidemiology studies and disease management in the region.

PMID- 29056518
TI  - Shaping children's healthy eating habits with food placements? Food placements of
      high and low nutritional value in cartoons, Children's BMI, food-related parental
      mediation strategies, and food choice.
AB  - Research on media induced food choices of children has not sufficiently
      investigated whether food placements of snacks high in nutritional value can
      strengthen children's healthy eating behavior. Furthermore, we lack knowledge
      about the moderating role of children's individual characteristics such as
      parental food-related mediation or BMI. The current study combines data from an
      experiment involving children with a survey of their parents. We exposed children
      to a cartoon either containing no food placements, placements of mandarins (i.e.,
      snack high in nutritional value), or placements of fruit gums (i.e., snack low in
      nutritional value). Afterwards, food consumption was measured by giving children
      the option to choose between fruit gums or mandarins. Children in both snack
      placement conditions showed stronger preference for the snack low in nutritional
      value (i.e., fruit gum) compared to the control group. Interestingly, neither
      restrictive nor active food-related mediation prevented the effects of the
      placements on children's choice of snacks low in nutritional value. Compared to
      children with a low BMI, children with high BMI levels had a stronger disposition
      to choose the fruit gums if a snack high in nutritional value (i.e., mandarin)
      was presented. Thus, making snacks high in nutritional attractive for children
      through media presentation might need stronger persuasive cues.

PMID- 29056519
TI  - An impedance-based cell contraction assay using human primary smooth muscle cells
      and fibroblasts.
AB  - INTRODUCTION: Many cell types (including muscle cells and fibroblasts) can
      contract at physiological conditions and their contractility may change during
      tissue injury and repair or other diseases such as allergy and asthma. The
      conventional gel contraction assay is commonly used to monitor the cellular
      contractility. It is a manual assay and the experiment usually takes hours even
      days to complete. As its readout is not always accurate and reliable, the gel
      contraction assay is often used to qualitatively (but not quantitatively)
      characterize cellular contractility under various conditions. METHOD: To overcome
      the limits of the gel contraction assay, we developed an impedance-based
      contraction assay using the xCELLigence RTCA MP system. This technology utilizes
      special 96-well E-plates with gold microelectrode arrays printed in individual
      wells to monitor cellular adhesion by recording the electrical impedance in real
      time. The impedance change (percentage vs. control) can be used as the readout
      for cellular contraction. RESULTS: We demonstrated that the impedance-based
      contraction assay can be performed within 2h. Using this new method, we
      quantitatively characterized the effects of several contractile stimulators and
      inhibitors on human primary bronchial smooth muscle cells and primary lung
      fibroblasts. DISCUSSION: The impedance-based contraction assay can be applied to
      both basic research and drug discovery for characterizing cellular contraction
      quantitatively. Because it has high throughput capacity and high reproducibility,
      the impedance-based contraction assay is useful for high throughput functional
      screening in drug industry.

PMID- 29056520
TI  - Characterization of immune cell, endothelial, and renal responses upon
      experimental human endotoxemia.
AB  - INTRODUCTION: Although the effects of relatively high concentrations of endotoxin
      on endothelial activation/dysfunction and kidney markers has been described in
      literature, detailed insight in the LPS concentration-effect relationship, the
      magnitude, variability and timing of the response, and potential effects of
      endotoxemia on the kidneys is lacking. A study was performed to assess the
      effects of low- to moderate dose (0.5, 1 or 2ng/kg) endotoxemia on the
      endothelium and kidneys as measured by a panel of novel highly sensitive kidney
      injury markers. METHODS: This was a randomized, double-blind, placebo-controlled
      study with single ascending doses of LPS (0.5, 1 or 2ng/kg) administered to
      healthy male volunteers (3 cohorts of 8 subjects, LPS:placebo 6:2). Endothelial
      measures included selectins, cell adhesion molecules, and thrombomodulin. Renal
      measures included novel, sensitive and specific biomarkers of acute kidney
      injury. RESULTS: Endotoxin exposure resulted in consistent LPS dose-dependent
      responses in inflammatory markers, E- and P- Selectin, VCAM1, ICAM1, and
      thrombomodulin. The observed biological responses were transient, reaching a
      level of significance of at least <0.01 in the highest dose group and with an
      effect size which was dependent on the administered LPS dose. LPS-induced
      inflammatory and endothelial effects did not translate into a change in renal
      damage biomarkers, although at 2ng/kg LPS, subtle and transient biomarker changes
      were observed that may relate to (subclinical) tubular damage. DISCUSSION: We
      demonstrated that administration of a single LPS dose of 2ng/kg to healthy
      volunteers results in significant inflammatory and endothelial responses, without
      inducing clinically relevant signs of kidney injury. These findings support the
      application of the human endotoxemia model in future clinical pharmacology
      studies.

PMID- 29056521
TI  - Study on the role of Hsa-miR-31-5p in hypertrophic scar formation and the
      mechanism.
AB  - Hypertrophic scar (HS) formation is associated with the fibrosis of fibrocytes
      caused by excessive extracellular matrix (ECM) synthesis and deposition, the
      initial event of HS formation. Our high throughput screen of miRNA expression
      profiles identified hsa-miR31-5p, whose transcription level was most
      differentially in normal skin fibroblasts (NS) and HS among other miRNAs. The
      level of hsa-miR31-5p in HS was significantly higher than in NS. In-vitro
      functional experiments showed hsa-miR31-5p knockdown remarkably suppressed the
      proliferation of hypertrophic scar fibroblasts (HSFBs) under hypoxia, promoted
      cell invasion, and inhibited the expression of Collagen I and III and Fibronectin
      (FN), suggesting that hsa-miR31-5p knockdown effectively reduces HS formation
      caused by excessive ECM synthesis and deposition in HSFBs under hypoxia.
      Mechanism study showed that the regulation of HS formation by hsa-miR31-5p was
      mediated by its target gene, factor-inhibiting HIF-1 (FIH): under hypoxia, hsa
      miR31-5p down-regulated FIH and thus increased the level of hypoxia inducible
      factor-1alpha (HIF-1alpha), which subsequently activated the HIF-1alpha fibrosis
      regulation pathway in HSFBs, and stimulated the proliferation and ECM synthesis
      in HSFBs, eventually resulting in fibrosis and scar formation. The data also show
      that knockdown of hsa-miR31-5p in HSFBs impaired the trend of increased
      proliferation, reduced invasion and excessive ECM synthesis and deposition caused
      by HIF-1a activation under hypoxia through upregulating FIH, indicating that
      knockdown of hsa-miR31-5p effectively inhibits the formation of HS. In
      conclusion, hsa-miR31 -5p plays an important role in HS formation by inhibiting
      FIH and regulating the HIF-1alpha pathway. Therefore, hsa-miR31 -5p may be a
      novel therapeutic target for HS.

PMID- 29056522
TI  - Electrochemical quantification of some water soluble vitamins in commercial multi
      vitamin using poly-amino acid caped by graphene quantum dots nanocomposite as
      dual signal amplification elements.
AB  - Rapid analyses of some water soluble vitamins (Vitamin B2, B9, and C) in
      commercial multi vitamins could be routinely performed in analytical
      laboratories. This study reports on the electropolymerization of a low toxic and
      biocompatible polymer "poly aspartic acid-graphene quantum dots" as a novel
      strategy for surface modification of glassy carbon electrode and preparation a
      new interface for measurement of selected vitamins in commercial multi vitamins.
      Electrochemical deposition, as a well-controlled synthesis procedure, has been
      used for subsequently layer-by-layer preparation of graphene quantum dots
      nanostructures on a poly aspartic acid using cyclic voltammetry techniques in the
      regime of -1.5 to 2 V. The field emission scanning electron microscopy indicated
      immobilization of graphene quantum dots onto poly aspartic acid film. The
      modified electrode possessed as an effective electroactivity for detection of
      water soluble vitamins by using cyclic voltammetry, chronoamperometry and
      differential pulse voltammetry. Enhancement of peak currents is ascribed to the
      fast heterogeneous electron transfer kinetics that arise from the synergistic
      coupling between the excellent properties of poly aspartic acid as semiconducting
      polymer, graphene quantum dots as high density of edge plane sites and chemical
      modification. Under the optimized analysis conditions, the prepared sensor for
      detection of VB2, VB9, and VC showed a low limit of quantification 0.22, 0.1, 0.1
      MUM, respectively.

PMID- 29056523
TI  - Role of paraventricular hypothalamic dopaminergic D1 receptors in food intake
      regulation of food-deprived rats.
AB  - Dopaminergic neurons play an important role on central regulatory mechanisms of
      feeding behavior. Dopamine receptors are distributed within the hypothalamus and
      densely localized in the paraventricular hypothalamic nucleus (PVN). From these
      ideas we postulated that PVN D1 receptors may play a role in regulating the food
      intake behavioral process. In this paper, we considered the effects of SKF38393,
      a D1 receptor agonist, and the D1 receptor antagonist (SCH23390), on food intake
      of conscious rats deprived of food for 24h. Our findings revealed that
      intraparaventricular injections of SKF383993 (0.3-5ug) stimulated food intake
      behavior in a dose dependent manner. This stimulatory effect of SKF3833 persisted
      over 2h of the monitoring period. The PVN injections of D1 receptor antagonist
      were associated with dose-dependent inhibition of food intake. SCH23390 (0.01ug)
      was also administered 5min before intraparaventricular injection of SKF3833. The
      results showed that SCH23390 suppressed stimulated food intake induced by
      SKF38393 (1.2ug). In conclusion, endogenous dopamine impact PVN D1 receptors and
      may be a factor in regulating the food intake behavioral process.

PMID- 29056524
TI  - Conventional versus chest-compression-only cardiopulmonary resuscitation by
      bystanders for children with out-of-hospital cardiac arrest.
AB  - AIM: It is unclear whether chest-compression-only cardiopulmonary resuscitation
      (CC-CPR) is therapeutically equivalent to conventional CPR for children with out
      of-hospital cardiac arrest (OHCA). We aimed to determine the association of CC
      CPR and conventional CPR with outcomes in discrete child patient populations with
      OHCA. METHODS: We analysed 6810 children (aged <18years) using Japanese registry
      from 2007 to 2014. Main outcomes measure was 30-day neurologically intact
      survival after OHCA, defined as Glasgow-Pittsburgh cerebral performance
      categories 1 or 2. RESULTS: In propensity score-matched children aged 1-17 years
      (n=2682), overall neurologically intact survival rate was significantly higher
      after conventional CPR than after CC-CPR (9.4% vs. 6.0%, P=0.001). However, there
      was no significant difference between the two CPR modalities in patients with
      cardiac aetiology (14.2% vs. 11.8%, P=0.32), initial shockable rhythm (35.3% vs.
      31.7%, P=0.59), or age >=8 years (12.4% vs. 9.8%, P=0.13). For matched infants
      (n=1994), no significant differences were observed in overall neurological intact
      survival between conventional CPR and CC-CPR (2.2% vs. 1.3%, P=0.17). In infant
      subgroup analyses, neurologically intact survival was similar between the CPR
      modalities for cardiac aetiology (0.3% vs. 1.0%; P=0.37) and for witnessed arrest
      (6.2% vs. 6.0%; P=0.98). CONCLUSIONS: In the majority of the paediatric
      subgroups, conventional CPR was associated with improved outcomes compared to CC
      CPR. CC-CPR was associated with 30-day neurologically intact survival similar to
      conventional CPR for children with OHCA aged >=8 years, for children aged 1-17
      years with cardiac aetiology or initial shockable rhythm, and for infants with
      cardiac aetiology or witnessed arrest.

PMID- 29056525
TI  - Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial
      pathways in pentylenetetrazol-kindled seizures.
AB  - Autophagy alterations have been observed in a variety of neurological disorders,
      however, very few studies have focused on autophagy alterations in epilepsy. The
      ketogenic diet (KD) likely ameliorates neuronal loss in several seizure models.
      However, whether this neuroprotective function occurs via starvation-induced
      autophagy and its prevalence in chronic kindled seizures remains unknown. The aim
      of this study was to determine the role of autophagy following seizure under KD,
      and the potential mechanism involved. Pentylenetetrazol (PTZ)-kindled rats, which
      were fed a Normal diet (ND) or KD, were pretreated with intraventricular
      infusions of saline, autophagy inducer rapamycin (RAP), or inhibitor 3
      methyladenine (3-MA). KD alleviated seizure severity, decreased the number of
      Fluoro-jade B (FJB)-positive cells in the hippocampus of kindled rats. These
      effects were abolished by 3-MA pretreatment. RAP pretreatment did not affect
      seizure severity, but decreased the number of FJB-positive cells in ND group. KD
      decreased the percentage of damaged mitochondria in kindled group. Hippocampal
      Beclin-1 was increased by KD in vehicle group. The autophagy proteins Atg5,
      Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3) II
      to LC3-I in kindled KD-fed rats were higher, and the autophagy substrate P62 was
      lower than those in the kindled ND-fed rats, indicating an increase in autophagy
      following KD. Pretreatment with RAP increased the level of LC3-II/LC3-I, and
      pretreatment with 3-MA increased the level of P62 in KD-fed rats. To further
      clarify the mechanism of autophagy protection, the levels of key mitochondria
      related molecules were examed. The results showed that mitochondrial cytochrome c
      was up-regulated, cytosolic cytochrome c and the downstream cleaved caspase-3 was
      down-regulated in KD-fed rats, indicating a decrease in mitochondrial apoptosis.
      Taken together, our results indicated that KD activates autophagic pathways and
      reduces brain injury during PTZ-kindled seizures. The neuroprotective effect of
      KD is likely exerted via a reduction of mitochondrial cytochrome c release.

PMID- 29056526
TI  - Relational concept learning in domestic dogs: Performance on a two-choice size
      discrimination task generalises to novel stimuli.
AB  - One central issue in the study of animal cognition concerns conceptual behaviour,
      where an organism categorises objects, events, and relationships so as to
      transfer previously learned rules to novel contexts. In this study, we
      investigated whether or not dogs demonstrate conceptual behaviour in the form of
      simple relational class concept learning. A two-choice visual discrimination task
      was used to assess if dogs are capable of simple relational class concept
      learning by generalising the same rule (i.e. circle is larger or smaller than) to
      various novel shapes. Eight purebred Lagotto Romagnolos were included in the
      study. The results demonstrated that they were capable of generalising a
      previously learned size discrimination rule to novel stimuli; however, there were
      differences in dog's generalization capabilities across certain shapes.
      Considering their unique relationship with humans, and their immediacy in
      everyday life, a better understanding of conceptual behaviour and generalising
      abilities in domestic dogs may have implications for training and management
      methods, as well as contributing to comparative psychology and applied ethology.

PMID- 29056527
TI  - Flow cytometry: An efficient method for antigenicity measurement and particle
      characterization on an adjuvanted vaccine candidate H4-IC31 for tuberculosis.
AB  - We have developed an accurate, precise and stability-indicating flow cytometry
      (FC) based assay to directly measure antigenicity of H4 protein (also known as
      HyVac4) in a vaccine formulation of H4-IC31, without desorbing the H4 protein
      from the IC31 adjuvant. This method involves immuno-staining of H4-IC31 complex
      with anti-H4 monoclonal antibodies (mAbs) followed by FC analysis. The assay is
      not only able to consistently measure H4 antigenicity levels in H4-IC31 stored
      under normal condition at 2-8 degrees C, but also able to detect changes in H4
      antigenicity after H4-IC31 undergoes heat stress or freeze-thawing. In addition,
      the FC method is able to characterize particle morphology while measuring
      antigenicity. The biological relevance of the changes in H4 antigenicity detected
      by the FC assay was supported by an in vitro cell based functional assay using
      human PBMCs to measure IFN-gamma (IFN-gamma) secretion upon re-stimulation with
      H4-IC31. Our results show that the FC based antigenicity assay can efficiently
      monitor the biological and physicochemical properties of H4-IC31 and is an
      indicator for adjuvanted vaccine product stability.

PMID- 29056528
TI  - Shipment of a photodynamic therapy agent into model membrane and its controlled
      release: A photophysical approach.
AB  - Harmine, an efficient cancer cell photosensitizer (PS), emits intense violet
      color when it is incorporated in well established self assembly based drug
      carrier formed by cationic surfactants of identical positive charge of head group
      but varying chain length, namely, dodecyltrimethylammonium bromide (DTAB),
      tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide
      (CTAB). Micelle entrapped drug emits in the UV region when it interacts with non
      toxic beta-cyclodextrin (beta-CD). Inspired by these unique
      fluorescence/structural switching properties of the anticancer drug, in the
      present work we have monitored the interplay of the drug between micelles and non
      toxic beta-CDs. We have observed that the model membranes formed by micelles
      differing in their hydrophobic chain length interact with the drug differently.
      Variation in the surfactant chain length plays an important role for structural
      switching i.e. in choosing a particular structural form of the drug that will be
      finally presented to their targets. The present study shows that in case of
      necessity, the bound drug molecule can be removed from its binding site in a
      controlled manner by the use of non-toxic beta-CD and it is exploited to serve a
      significant purpose for the removal of excess/unused adsorbed drugs from the
      model cell membranes. We believe this kind of beta-CD driven translocation of
      drugs monitored by fluorescence switching may find possible applications in
      controlled release of the drug inside cells.

PMID- 29056529
TI  - Co-synthesis of medium-chain-length polyhydroxyalkanoates and CdS quantum dots
      nanoparticles in Pseudomonas putida KT2440.
AB  - Microbial polymers and nanomaterials production is a promising alternative for
      sustainable bioeconomics. To this end, we used Pseudomonas putida KT2440 as a
      cell factory in batch cultures to coproduce two important nanotechnology
      materials- medium-chain-length (MCL)-polyhydroxyalkanoates (PHAs) and CdS
      fluorescent nanoparticles (i.e. quantum dots [QDots]). Due to high cadmium
      resistance, biomass and PHA yields were almost unaffected by coproduction
      conditions. Fluorescent nanocrystal biosynthesis was possible only in presence of
      cysteine. Furthermore, this process took place exclusively in the cell,
      displaying the classical emission spectra of CdS QDots under UV-light exposure.
      Cell fluorescence, zeta potential values, and particles size of QDots depended on
      cadmium concentration and exposure time. Using standard PHA-extraction
      procedures, the biosynthesized QDots remained associated with the biomass, and
      the resulting PHAs presented no traces of CdS QDots. Transmission electron
      microscopy located the synthesized PHAs in the cell cytoplasm, whereas CdS
      nanocrystals were most likely located within the periplasmic space, exhibiting no
      apparent interaction. This is the first report presenting the microbial
      coproduction of MCL-PHAs and CdS QDots in P. putida KT2440, thus constituting a
      foundation for further bioprocess developments and strain engineering towards the
      efficient synthesis of these highly relevant bioproducts for nanotechnology.

PMID- 29056530
TI  - The effect of combined diet and exercise intervention on body weight and the
      serum GPIHBP1 concentration in overweight/obese middle-aged women.
AB  - BACKGROUND: The relationship between the effects of diet and exercise
      intervention and the body weight associated with the serum lipoprotein lipase
      (LPL), hepatic triglyceride lipase (HTGL) and glycosylphosphatidylinositol
      anchored high density lipoprotein binding protein 1 (GPIHBP1) concentrations has
      not been elucidated. METHODS: Sixty-six overweight/obese middle aged women were
      assigned to the diet and exercise intervention for 4months. They were divided
      into 2 groups followed by the body mass index (BMI) decreased >3% (n=41) and <3%
      (n=25). Serum lipids, lipoproteins and the LPL, HTGL, GPIHBP1 concentrations were
      determined. RESULTS: The cases in which the BMI decreased >3% exhibited
      significant improvement of diagnostic markers compared with the cases with <3%
      decrease after the intervention. The LPL concentration did not significantly
      change, but GPIHBP1 increased significantly after the intervention. The increased
      GPIHBP1 was significantly associated with decreased body weight. Multiple
      regression analysis indicated a strong association between GPIHBP1 and percentage
      of body fat. CONCLUSIONS: The diet and exercise intervention significantly
      increased the serum GPIHBP1 concentration in association with a decrease in body
      weight and percentage of body fat. These results suggest that GPIHBP1 is a better
      marker for body weight decrease than LPL.

PMID- 29056532
TI  - LAMP3 regulates hepatic lipid metabolism through activating PI3K/Akt pathway.
AB  - Lysosome associated membrane protein 3 (LAMP3), a highly glycosylated protein, is
      one member of the LAMPs family. LAMPs family plays a critical role in the
      autolysosome fusion process. Autophagy was recently confirmed to regulate hepatic
      lipolysis. However, the physiological function of LAMP3 in lipid metabolism is
      not clear. In the current study, we discovered that the LAMP3 expression level
      was higher in the liver tissues of non-alcoholic fatty liver disease (NAFLD)
      patients and high-fat diet and ob/ob mice than in the matched control groups.
      LAMP3 expression was also obviously increased in hepatocellular carcinoma (HCC)
      cells treated with free fatty acids. Moreover, marked accumulation of
      intracellular lipid droplets and triglycerides (TG) was observed after LAMP3
      overexpression in HCC cells. Further study showed that LAMP3 overexpression
      activated Akt and upregulated the expression of the lipogenic enzymes FASN and
      SCD-1 in HepG2 cells. Additionally, the increased TG content induced by LAMP3
      overexpression was attenuated by treatment with a PI3K/Akt pathway inhibitor. Our
      findings demonstrated that LAMP3 is an important regulator of hepatic lipid
      metabolism, which provides a line of evidence for taking LAMP3 as a drug target
      in lipid metabolism disorder-associated diseases, such as NAFLD and obesity.

PMID- 29056531
TI  - Concordance between direct and indirect measurements of free 25-OH vitamin D.
AB  - : At present, data comparing the quantification methods for measurement of free
      vitamin D (direct assay [direct 25-OHDF] and estimated by calculation [calculated
      25-OHDF]), are scarce. The aim of this study was to analyse the concordance
      between these two methods of 25-OHDF analysis (direct vs. calculated). METHODS:
      Serum values of total 25-OHD (25-OHDT), vitamin D binding protein (DBP) (by R&D
      Systems ELISA), calculated 25-OHDF (by DBP, albumin and 25-OHDT) and direct 25
      OHDF (by DIAsource ELISA) were analysed in 173 healthy women (aged 35-45years).
      Assessment of concordance was evaluated by the Bland-Altman plot and the total
      deviation index (TDI). RESULTS: The mean values of calculated and direct 25-OHDF
      in these subjects were 5.27+/-2.5 and 3.83+/-1.01pg/mL, respectively. We found
      significantly lower values of 25-OHDF on comparing subjects with and without
      vitamin D deficiency, independently of the method used. The total deviation index
      evaluated by the Bland-Altman plot showed low concordance for both measurements.
      Only low 25-OHDF levels were concordant. CONCLUSIONS: This study shows that the
      concordance between these two methods of 25-OHDF analysis is low and has a
      concentration dependent bias. Further studies are necessary to clarify the
      reference values and the indications for 25-OHDF measurement.

PMID- 29056533
TI  - VERNALIZATION1 Modulates Root System Architecture in Wheat and Barley.

PMID- 29056534
TI  - Comorbidity in Lung Cancer: A Prospective Cohort Study of Self-Reported versus
      Register-Based Comorbidity.
AB  - OBJECTIVE: Comorbidity is a debated prognosticator in lung cancer. Results are
      conflicting, and the variety in study designs and inclusion criteria hampers
      direct comparison of available studies. So far, methods for generation of data on
      lung cancer comorbidity have attracted little attention. We evaluated whether
      self-reported comorbidity and register-based comorbidity are of comparable
      quality. METHODS: In a prospective study, we evaluated paired data sets on self
      reported versus register-based comorbidity to detect whether any data asymmetry
      could be related to the data collection methods. We evaluated the Charlson
      comorbidity index and the simplified comorbidity score as predictors of overall
      survival (OS) in lung cancer to test whether our findings would affect outcome.
      RESULTS: In a cohort of 336 patients with lung cancer and 125 patients in whom
      cancer was suspected but who were determined to be cancer-free, we demonstrated a
      significant underreporting of self-reported comorbidities compared with register
      based comorbidities. Furthermore, we demonstrated that an association between
      comorbidity and OS can be detected only by using register-based data and only by
      the simplified comorbidity score (hazard rate = 1.6, 95% confidence interval: 1.0
      2.5, p = 0.03). The results remained significant after adjustment for the
      relevant clinicopathological characteristics (hazard rate = 1.8, 95% confidence
      interval: 1.1-3.3, p = 0.028). An association between comorbidity and OS could
      not be detected by using either the self-reported data or the Charlson
      comorbidity index. CONCLUSIONS: In this cohort of patients in whom cancer was
      suspected, comorbidity estimations varied depending on the data collection method
      used; similarly, the data collection method could affect the association between
      comorbidity and OS.

PMID- 29056535
TI  - Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study,
      mutation profile and description of twenty novel mutations.
AB  - Maturity onset diabetes is a genetic form of diabetes mellitus characterized by
      an early age at onset and several etiologic genes for this form of diabetes have
      been identified in many patients. Maturity onset diabetes type 2 [MODY2
      (#125851)] caused by mutations in the glucokinase gene (GCK). Although its
      prevalence is not clear, it is estimated that 1%-2% of patients with diabetes
      have the monogenic form. The aim of this study was to evaluate the molecular
      spectrum of GCK gene mutations in 177 Turkish MODY type 2 patients. Mutations in
      the GCK gene were identified in 79 out of 177. All mutant alleles were
      identified, including 45 different GCK mutations, 20 of which were novel.

PMID- 29056536
TI  - Predicting risk of pelvic floor disorders 12 and 20 years after delivery.
AB  - BACKGROUND: Little progress has been made in the prevention of pelvic floor
      disorders, despite their significant health and economic impact. The
      identification of women who are at risk remains a key element in targeting
      prevention and planning health resource allocation strategies. Although events
      around the time of childbirth are recognized clinically as important predictors,
      it is difficult to counsel women and to intervene around the time of childbirth
      because of an inability to convey a patient's risk accurately in the presence of
      multiple risk factors and the long time lapse, which is often decades, between
      obstetric events and the onset of pelvic floor disorders later in life.
      Prediction models and scoring systems have been used in other areas of medicine
      to identify patients who are at risk for chronic diseases. Models have been
      developed for use before delivery that predict short-term risk of pelvic floor
      disorders after childbirth, but no models that predict long-term risk exist.
      OBJECTIVE: The purpose of this study was to use variables that are known before
      and during childbirth to develop and validate prognostic models that will
      estimate the risks of these disorders 12 and 20 years after delivery. STUDY
      DESIGN: Obstetric variables were collected from 2 cohorts: (1) women who gave
      birth in the United Kingdom and New Zealand (n=3763) and (2) women from the
      Swedish Medical Birth Register (n=4991). Pelvic floor disorders were self
      reported 12 years after childbirth in the United Kingdom/New Zealand cohort and
      20 years after childbirth in the Swedish Register. The cohorts were split so that
      data during the first half of the cohort's time period were used to fit
      prediction models, and validation was performed from the second half (temporal
      validation). Because there is currently no consensus on how to best define pelvic
      floor disorders from a patient's perspective, we chose to fit the data for each
      model using multiple outcome definitions for prolapse, urinary incontinence,
      fecal incontinence, >=1 pelvic floor disorder, and >=2 pelvic floor disorders.
      Model accuracy was measured in the following manner: (1) by ranking an
      individual's risk among all subjects in the cohort (discrimination) with the use
      of a concordance index and (2) by observing whether the predicted probability was
      too high or low (calibration) at a range of predicted probabilities with the use
      of visual plots. RESULTS: Models were able to discriminate between women who
      experienced bothersome symptoms or received treatment at 12 and 20 years,
      respectively, for pelvic organ prolapse (concordance indices, 0.570, 0.627),
      urinary incontinence (concordance indices, 0.653, 0.689), fecal incontinence
      (concordance indices, 0.618, 0.676), >=1 pelvic floor disorders (concordance
      indices, 0.639, 0.675), and >=2 pelvic floor disorders (concordance indices,
      0.635, 0.619). Route of delivery and family history of each pelvic floor disorder
      were strong predictors in most models. Urinary incontinence before and during the
      index pregnancy was a strong predictor for the development of all pelvic floor
      disorders in most models 12 years after delivery. The 12- and 20-year bothersome
      symptoms or treatment for prolapse models were accurate when predictions were
      provided for risk from 0% to approximately 15%. The 12- and 20-year primiparous
      model began to over predict when risk rates reached 20%. When we predicted
      bothersome symptoms or treatment for urinary incontinence, the 12-year models
      were accurate when predictions ranged from approximately 5-60%; the 20-year
      primiparous models were accurate from 5% and 80%. For bothersome symptoms or
      treatment for fecal incontinence, the 12- and 20-year models were accurate from 1
      15% risk and began to over predict at rates at >15% and 20%, respectively.
      CONCLUSION: Models may provide an opportunity before birth to identify women who
      are at low risk of the development of pelvic floor disorders and may provide
      institute prevention strategies such as pelvic floor muscle training, weight
      control, or elective cesarean section for women who are at higher risk. Models
      are provided at http://riskcalc.org/UR_CHOICE/.

PMID- 29056537
TI  - Male partner reproductive coercion among women veterans.
AB  - BACKGROUND: Male partner reproductive coercion is defined as male partners'
      attempts to promote pregnancy through interference with women's contraceptive
      behaviors and reproductive decision-making. Male partners may try to promote
      pregnancy through birth control sabotage such as taking away or destroying their
      partners' contraceptives, refusing to wear condoms, and/or verbally pressuring
      their partners to abstain from contraceptive use. Reproductive coercion is
      associated with an elevated risk for unintended pregnancy. Women who experience
      intimate partner violence, who are in racial/ethnic minorities, and who are of
      lower socioeconomic status are more likely to experience reproductive coercion.
      Women veterans who use Veterans Affairs for health care may be particularly
      vulnerable to reproductive coercion because they are disproportionally from
      racial/ethnic minority groups and experience high rates of intimate partner
      violence. OBJECTIVES: We sought to examine the prevalence, correlates, and impact
      of reproductive coercion among women veterans who are served by the Veterans
      Affairs healthcare system. STUDY DESIGN: We analyzed data from a national
      telephone survey of women veterans aged 18-44 years, with no history of
      sterilization or hysterectomy, who had received care within the Veterans Affairs
      system in the previous 12 months. Participants who had sex with men in the last
      year were asked if they experienced male partner reproductive coercion. Adjusted
      logistic regression was used to examine the relationship between participant
      characteristics and male partner reproductive coercion and the relationship
      between reproductive coercion and the outcomes of contraceptive method used at
      last sex and pregnancy and unintended pregnancy in the last year. RESULTS: Among
      the 1241 women veterans in our study cohort, 11% reported experiencing male
      partner reproductive coercion in the past year. Black women, younger women, and
      single women were more likely to report reproductive coercion than their white,
      older, and married counterparts. Women who experienced military sexual trauma
      were also more likely to report reproductive coercion compared with women who did
      not report military sexual trauma. In adjusted analyses, compared with women who
      did not experience reproductive coercion, those who did were less likely at last
      sex to have used any method of contraception (76% vs 80%; adjusted odds ratio,
      0.61; 95% confidence interval, 0.38-0.96), prescription contraception (43% vs
      55%; adjusted odds ratio, 0.62; 95% confidence interval, 0.43-0.91), and their
      ideal method of contraception (35% vs 45%; adjusted odds ratio, 0.63; 95%
      confidence interval, 0.43-0.93). Those who reported coercion were more likely to
      have had a pregnancy in the last year (14% vs 10%; adjusted odds ratio, 2.07; 95%
      confidence interval, 1.17-3.64); there were no significant differences in
      unintended pregnancy by coercion status (6% vs 4%; adjusted odds ratio, 1.63; 95%
      confidence interval, 0.71-3.76). CONCLUSION: Eleven percent of women veterans in
      our sample experienced male partner reproductive coercion, which may impact their
      use of contraception and ability to prevent pregnancy.

PMID- 29056538
TI  - The role of RAS mutations in MLL-rearranged leukaemia: A path to intervention?
AB  - Childhood acute lymphoblastic leukaemia (ALL) with MLL rearrangement (MLL-r) is
      an aggressive disease still associated with a high mortality rate. Recent
      investigations have identified co-operating mutations in the RAS pathway and
      although the functional consequences of these mutations are not yet fully
      understood, aberrant regulation of RAS pathway signalling at both transcriptional
      and protein levels is observed. Studies investigating the efficacy of specific
      inhibitors of this pathway, e.g. MEK-inhibitors, have also achieved encouraging
      results. In this context, this mini-review summarizes the available data
      surrounding MLL-r infant ALL with RAS mutation in relation to other well-known
      features of this intriguing disease.

PMID- 29056539
TI  - Tumor cell-associated immune checkpoint molecules - Drivers of malignancy and
      stemness.
AB  - Inhibitory or stimulatory immune checkpoint molecules are expressed on a sizeable
      fraction of tumor cells in different tumor types. It was thought that the main
      function of tumor cell-associated immune checkpoint molecules would be the
      modulation (down- or upregulation) of antitumor immune responses. In recent
      years, however, it has become clear that the expression of immune checkpoint
      molecules on tumor cells has important consequences on the biology of the tumor
      cells themselves. In particular, a causal relationship between the expression of
      these molecules and the acquisition of malignant traits has been demonstrated.
      Thus, immune checkpoint molecules have been shown to promote the epithelial
      mesenchymal transition of tumor cells, the acquisition of tumor-initiating
      potential and resistance to apoptosis and antitumor drugs, as well as the
      propensity to disseminate and metastasize. Herein, we review this evidence, with
      a main focus on PD-L1, the most intensively investigated tumor cell-associated
      immune checkpoint molecule and for which most information is available. Then, we
      discuss more concisely other tumor cell-associated immune checkpoint molecules
      that have also been shown to induce the acquisition of malignant traits, such as
      PD-1, B7-H3, B7-H4, Tim-3, CD70, CD28, CD137, CD40 and CD47. Open questions in
      this field as well as some therapeutic approaches that can be derived from this
      knowledge, are also addressed.

PMID- 29056540
TI  - A Phase II Study of Methotrexate, Etoposide, Dexamethasone and Pegaspargase
      Sandwiched with Radiotherapy in the Treatment of Newly Diagnosed, Stage IE to IIE
      Extranodal Natural-Killer/T-Cell Lymphoma, Nasal-Type.
AB  - BACKGROUND: A phase II study of methotrexate, etoposide, dexamethasone, and
      pegaspargase (MESA) sandwiched with radiotherapy for newly diagnosed, stage IE
      IIE extranodal natural-killer/T-cell lymphoma, nasal-type (ENKTL) was conducted
      to explore its clinical efficacy and safety, as well as novel serum biomarkers
      upon anti-metabolic treatment. METHODS: Four cycles of MESA sandwiched with
      radiotherapy were administered. The primary end point was the overall response
      rate (ORR). Serum metabolomic profiles were assessed by liquid chromatography
      mass spectrometry, with specific metabolites quantified by targeted metabolic
      analysis. FINDINGS: Forty patients were enrolled and the ORR was 92.1% (95%CI,
      83.1%-100.0%). The 2-year progression-free survival (PFS) rate was 89.1% and
      overall survival (OS) rate was 92.0%. Grade 3/4 non-hematologic and hematologic
      toxicities were observed in 17 (42.5%) and 26 patients (65.0%) during
      chemotherapy, and in 9 (22.5%) and 0 (0.0%) patients during radiotherapy,
      respectively. Fifty-six significantly decreased and 59 increased metabolites were
      identified in ENKTL, as compared to healthy volunteers. A predictive principal
      components analysis model of asparaginase-associated metabolites, asparaginase
      associated metabolic score (AspM), was established, including alanine, aspartate,
      glutamate, and succinic acid. Patients with high AspM score displayed superior
      survival and prognostic significance of AspM was validated in a historical cohort
      of early and advanced-stage ENKTL treated with asparaginase-based regimens.
      Multivariate analysis confirmed AspM as a prognostic score independent of PINK
      and PINK combined with Epstein-Barr virus DNA. INTERPRETATION: MESA sandwiched
      with radiotherapy is an effective and safe regimen for early-stage ENKTL. AspM
      score may be a promising prognostic index of serum metabolites in addition to
      clinical prognostic index in ENKTL.

PMID- 29056541
TI  - Application of Convolutional Neural Networks in the Diagnosis of Helicobacter
      pylori Infection Based on Endoscopic Images.
AB  - BACKGROUND AND AIMS: The role of artificial intelligence in the diagnosis of
      Helicobacter pylori gastritis based on endoscopic images has not been evaluated.
      We constructed a convolutional neural network (CNN), and evaluated its ability to
      diagnose H. pylori infection. METHODS: A 22-layer, deep CNN was pre-trained and
      fine-tuned on a dataset of 32,208 images either positive or negative for H.
      pylori (first CNN). Another CNN was trained using images classified according to
      8 anatomical locations (secondary CNN). A separate test data set (11,481 images
      from 397 patients) was evaluated by the CNN, and 23 endoscopists, independently.
      RESULTS: The sensitivity, specificity, accuracy, and diagnostic time were 81.9%,
      83.4%, 83.1%, and 198s, respectively, for the first CNN, and 88.9%, 87.4%, 87.7%,
      and 194s, respectively, for the secondary CNN. These values for the 23
      endoscopists were 79.0%, 83.2%, 82.4%, and 230+/-65min (85.2%, 89.3%, 88.6%, and
      253+/-92min by 6 board-certified endoscopists), respectively. The secondary CNN
      had a significantly higher accuracy than endoscopists (by 5.3%; 95% CI, 0.3
      10.2). CONCLUSION: H. pylori gastritis could be diagnosed based on endoscopic
      images using CNN with higher accuracy and in a considerably shorter time compared
      to manual diagnosis by endoscopists.

PMID- 29056542
TI  - Inhibition of rabies virus replication by interferon-stimulated gene 15 and its
      activating enzyme UBA7.
AB  - It was reported that ISG15 and its activating enzyme UBA7 have antiviral
      functions. However, there is no study to demonstrate whether ISG15 and UBA7 have
      anti-rabies virus function. In the current study, In vivo and in vitro anti
      rabies virus function of ISG15 and UBA7 were investigated using RNAi technology.
      The results showed that shRNA knock-down of expression of ISG15 and UBA7
      increased the titers of RABV in neuroblastoma cell line NA and microglial cell
      line BV-2 cells and shRNA knockdown of ISG15 conjugation alleviates the IFN
      induced inhibition of RABV gene expression in vitro. Lentiviral vector mediated
      shRNA knock-down of expression of ISG15 and UBA7 increased the titers of RABV in
      mouse brains and decreased the survivorship of mice. The study showed that ISG15
      and UBA7 inhibit RABV replication in vitro and in vivo. To our knowledge, we for
      the first time documented the anti-RABV function of ISG15 and UBA7, which may
      provide a means of understanding the pathogenesis of rabies and improving
      therapeutic methods.

PMID- 29056543
TI  - Utility of the ultra-high-resolution 3-dimensional mapping catheter for isolated
      pulmonary vein reentrant tachycardia.

PMID- 29056544
TI  - Lack of prognostic value of atrial arrhythmia inducibility and change in
      inducibility status after catheter ablation of atrial fibrillation.
AB  - BACKGROUND: Previous studies have suggested a role of atrial arrhythmia
      inducibility as an endpoint of catheter ablation of atrial fibrillation (AF). The
      prognostic value of noninducibility after ablation and of a change in
      inducibility status has not been investigated in large studies. OBJECTIVE: The
      purpose of this study was to evaluate the prognostic role of noninducibility and
      of a change in inducibility status after ablation of AF. METHODS: We studied 305
      consecutive patients with AF (66% paroxysmal) undergoing antral pulmonary vein
      (PV) isolation plus non-PV triggers ablation. All patients underwent a
      standardized induction protocol before and after ablation from the coronary sinus
      and right atrium: 15-beat burst pacing at 250 ms and decrementing to 180 ms (up
      to 20 MUg/min isoproterenol). Inducibility was defined as any sustained AF or
      organized atrial tachycardia (AT) lasting >2 minutes. RESULTS: A total of 197
      patients (65%) had inducible AF/AT at baseline compared to 118 (39%) after
      ablation. One hundred seven patients (57%) changed their inducibility status from
      inducible preablation to noninducible postablation. After 19 +/- 7 months of
      follow-up, 212 patients (70%) remained free from any recurrent AF/AT.
      Noninducibility of AF/AT postablation (log-rank P = .236) or change in
      inducibility status (log-rank P = .429) was not associated with reduced risk of
      recurrent AF/AT. Results were consistent across the paroxysmal and nonparoxysmal
      subgroups. CONCLUSION: Noninducibility of atrial arrhythmia or change in
      inducibility status after PV isolation and non-PV trigger ablation is not
      associated with long-term freedom from recurrent arrhythmia and should not be
      used as an ablation endpoint or to support the appropriateness of additional
      ablation lesion sets.

PMID- 29056545
TI  - Characterization of the LECT2 gene and its protective effects against microbial
      infection via large lymphocytes in Lampetra japonica.
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional protein of the
      innate immune system that defends against bacterial infections and chemotactic
      activity. However, its precise function in lamprey remains unclear. In this
      study, a novel LECT2 gene was first cloned from Lampetra japonica. The full
      length cDNA sequence of L-LECT2 consists of a 606-bp ORF encoding a protein of
      201 amino acid residues. L-LECT2 has greater than 50% sequence identity with its
      homologs in jawed vertebrates. FACS and immunohistochemistry assays were used to
      determine that the L-LECT2 protein was primarily distributed in the intestines
      and supraneural body tissues of lamprey, also marginally detectable in
      leukocytes. However, the expression of L-LECT2 was differentially upregulated in
      the intestines and heart after treatment with LPS. The recombinant L-LECT2
      resulted in significant promoting migration of the leukocytes in vitro. Our data
      demonstrate that L-LECT2 treatment could enhance phagocytosis in lamprey large
      lymphocytes. Thus, our results suggest that LECT2 can modulate the host defense
      in lamprey and mediate antibacterial protection against E.coli through large
      lymphocytes.

PMID- 29056546
TI  - Extended fasting does not affect the liver innate immune response in rainbow
      trout.
AB  - Activation of immune response pathway is energy demanding. We tested the
      hypothesis that negative energy balance will curtail the liver's capacity to
      evoke an immune response in rainbow trout (Oncorhynchus mykiss). Fish were either
      fed or fasted for 118 d and challenged with lipopolysaccharide (LPS) to determine
      the liver capacity to elicit an immune response. Fasting led to negative specific
      growth rate, reduced tissue metabolite levels, and higher transcript abundance of
      SOCS-2. LPS treatment increased the liver transcript abundances of IL-1beta and
      IL-8 and serum amyloid protein A, while SOCS-2 was reduced. LPS lowered plasma
      cortisol level only in the fasted fish, but did not affect liver glucocorticoid
      or mineralocorticoid receptor protein expressions. Extended fasting did not
      suppress the liver capacity to evoke an immune response. Upregulation of liver
      SOCS-2 may be playing a key role in the energy repartitioning, thereby
      facilitating immune response activation despite extended fasting in trout.

PMID- 29056547
TI  - Porcine serum amyloid A3 is expressed in extrahepatic tissues and facilitates
      viral replication during porcine respiratory and reproductive syndrome virus
      infection.
AB  - Serum amyloid A (SAA) is an acute phase protein that is expressed rapidly in
      response to infection and inflammation in vertebrates. Here, we detected the
      expression of porcine SAA3, an isoform of porcine SAA, during porcine respiratory
      and reproductive syndrome virus (PRRSV) infection, which is a major threat to the
      pig industry. In response to PRRSV infection, porcine SAA3 expression was
      upregulated significantly in porcine pulmonary alveolar macrophages and in
      extrahepatic tissues, including the lungs and inguinal, mandibular, and hilar
      lymph nodes, which were affected mainly by PRRSV infection, demonstrating that
      porcine SAA3 is a tissue-derived isoform that is induced in extrahepatic tissues
      during the acute phase response. Overexpression of porcine SAA3 increased PRRSV
      titers in cultured cells, and the exogenous administration of porcine SAA3
      facilitated PRRSV adsorption to cells, suggesting that porcine SAA3 assists PRRSV
      replication. Our data provide insights into the role of porcine SAA3 during PRRSV
      infection.

PMID- 29056548
TI  - Human induced pluripotent stem cell-derived lung progenitor and alveolar
      epithelial cells attenuate hyperoxia-induced lung injury.
AB  - BACKGROUND AIMS: Bronchopulmonary dysplasia (BPD), a chronic lung disease
      characterized by disrupted lung growth, is the most common complication in
      extreme premature infants. BPD leads to persistent pulmonary disease later in
      life. Alveolar epithelial type 2 cells (AEC2s), a subset of which represent
      distal lung progenitor cells (LPCs), promote normal lung growth and repair. AEC2
      depletion may contribute to persistent lung injury in BPD. We hypothesized that
      induced pluripotent stem cell (iPSC)-derived AECs prevent lung damage in
      experimental oxygen-induced BPD. METHODS: Mouse AECs (mAECs), miPSCs/mouse
      embryonic stem sells, human umbilical cord mesenchymal stromal cells (hUCMSCs),
      human (h)iPSCs, hiPSC-derived LPCs and hiPSC-derived AECs were delivered
      intratracheally to hyperoxia-exposed newborn mice. Cells were pre-labeled with a
      red fluorescent dye for in vivo tracking. RESULTS: Airway delivery of primary
      mAECs and undifferentiated murine pluripotent cells prevented hyperoxia-induced
      impairment in lung function and alveolar growth in neonatal mice. Similar to
      hUCMSC therapy, undifferentiated hiPSCs also preserved lung function and alveolar
      growth in hyperoxia-exposed neonatal NOD/SCID mice. Long-term assessment of hiPSC
      administration revealed local teratoma formation and cellular infiltration in
      various organs. To develop a clinically relevant cell therapy, we used a highly
      efficient method to differentiate hiPSCs into a homogenous population of AEC2s.
      Airway delivery of hiPSC-derived AEC2s and hiPSC-derived LPCs, improved lung
      function and structure and resulted in long-term engraftment without evidence of
      tumor formation. CONCLUSIONS: hiPSC-derived AEC2 therapy appears effective and
      safe in this model and warrants further exploration as a therapeutic option for
      BPD and other lung diseases characterized by AEC injury.

PMID- 29056549
TI  - Adoptive transfer of natural killer cells in combination with chemotherapy
      improves outcomes of patients with locally advanced colon carcinoma.
AB  - BACKGROUND: Despite the availability of multiple treatment strategies, patients
      with advanced colon carcinoma (CC) have poor prognoses. The aim of this study was
      to evaluate the efficacy and safety of natural killer (NK) cell therapy in
      combination with chemotherapy in patients with locally advanced CC. METHODS: We
      assessed the cytotoxicity of NK cells to CC cells (CCs) and CC stem cells (CSCs)
      pre-treated with 5-fluorouracil or oxaliplatin in vitro. Then, an open-label
      cohort study was conducted with locally advanced CC patients who had received
      radical resection. Patients received either NK cell therapy combined with
      chemotherapy (NK cell group, 27 patients) or pure chemotherapy (control group, 33
      patients). Progression-free survival (PFS), overall survival (OS) and adverse
      effects were investigated. RESULTS: Chemotherapy sensitized CCs and CSCs to NK
      cell cytotoxicity through regulation of NK cell-activating/inhibitory receptor
      ligands. Poorly differentiated CCs were more susceptible to NK cells than well
      differentiated ones. In the cohort study, the 5-year PFS and OS rates in the NK
      cell group were significantly higher than those in the control group (51.1%
      versus 35%, P= 0.044; 72.5% versus 51.6%, P= 0.037, respectively). Among patients
      with poorly differentiated carcinomas and low expression of human leukocyte
      antigen (HLA)-1, the median PFS in the NK cell group versus the control group was
      23.5 versus 12.1 months (P= 0.0475) and 33.1 versus 18.5 months (P= 0.045),
      respectively. No significant adverse reactions were reported. CONCLUSION: NK cell
      therapy in combination with chemotherapy in locally advanced CC prevented
      recurrence and prolonged survival with acceptable adverse effects, especially for
      poorly differentiated carcinomas.

PMID- 29056550
TI  - Piperine in combination with quercetin halt 6-OHDA induced neurodegeneration in
      experimental rats: Biochemical and neurochemical evidences.
AB  - Parkinson's disease (PD) is a multifactorial neurological disorder caused by
      selective dopaminergic neuronal loss. Quercetin (QC) in combination with piperine
      (bioenhancer) acts as potential antioxidant, anti-inflammatory and
      neuroprotective against 6-OHDA rat model of PD. Rats were injected 6-OHDA
      (8MUg/2MUl, saline) unilaterally, intranigrally once into right SNpc. Pre
      treatment with QC (25 and 50mg/kg, p.o.) alone and combination of QC (25mg/kg,
      p.o.) with piperine (2.5mg/kg, p.o.) were given for 14days starting from 8th day
      of 6-OHDA infusion. Post lesions were confirmed by rotational behavior with
      amphetamine (2.5mg/kg, i.p.) and motor coordination was assessed by narrow beam
      walk, open field and rotarod apparatus on the weekly basis. On 22nd day, animals
      were sacrificed and striatum homogenates were used for biochemical (LPO, GSH,
      Nitrite), neuroinflammatory (TNF-alpha, IL-1 beta and IL-6) and neurotransmitter
      (dopamine, norepinephrine, serotonin, GABA, glutamate) analysis. Rats pre-treated
      with QC alone and in combination with piperine have significantly attenuated the
      6-OHDA induced rotational behavior and motor deficits. Further, these drugs have
      significantly improved antioxidant potential, decreased striatal proinflammatory
      cytokines level as well as restored neurotransmitters level. The neuroprotective
      enhancement of QC along with piperine is attributed through antioxidant, anti
      inflammatory and preventing neurotransmitter alteration mechanisms.

PMID- 29056551
TI  - MAP Kinase Cascades Regulate the Cold Response by Modulating ICE1 Protein
      Stability.
AB  - Mitogen-activated protein kinase cascades are important signaling modules that
      convert environmental stimuli into cellular responses. We show that MPK3, MPK4,
      and MPK6 are rapidly activated after cold treatment. The mpk3 and mpk6 mutants
      display increased expression of CBF genes and enhanced freezing tolerance,
      whereas constitutive activation of the MKK4/5-MPK3/6 cascade in plants causes
      reduced expression of CBF genes and hypersensitivity to freezing, suggesting that
      the MKK4/5-MPK3/6 cascade negatively regulates the cold response. MPK3 and MPK6
      can phosphorylate ICE1, a basic-helix-loop-helix transcription factor that
      regulates the expression of CBF genes, and the phosphorylation promotes the
      degradation of ICE1. Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively
      suppresses MPK3 and MPK6 activities and has a positive role in the cold response.
      Furthermore, the MAPKKK YDA and two calcium/calmodulin-regulated receptor-like
      kinases, CRLK1 and CRLK2, negatively modulate the cold activation of MPK3/6. Our
      results uncover important roles of MAPK cascades in the regulation of plant cold
      response.

PMID- 29056553
TI  - MPK3- and MPK6-Mediated ICE1 Phosphorylation Negatively Regulates ICE1 Stability
      and Freezing Tolerance in Arabidopsis.
AB  - Low temperatures affect plant growth, development, productivity, and ecological
      distribution. Expression of the C-repeat-binding factor (CBF) transcription
      factors is induced by cold stress, which in turn activates downstream cold
      responsive (COR) genes that are required for the acquisition of freezing
      tolerance. Inducer of CBF expression 1 (ICE1) is a master regulator of CBFs, and
      ICE1 stability is crucial for its function. However, the regulation of ICE1 is
      not well understood. Here, we report that mitogen-activated protein kinase 3
      (MPK3) and MPK6 interact with and phosphorylate ICE1, which reduces its stability
      and transcriptional activity. Consistently, the mpk3 and mpk6 single mutants and
      the mpk3 mpk6 double mutants show enhanced freezing tolerance, whereas MPK3/MPK6
      activation attenuates freezing tolerance. Phosphor-inactive mutations of ICE1
      complement freezing sensitivity in the ice1-2 mutant. These combined results
      indicate that MPK3/MPK6 phosphorylate and destabilize ICE1, which negatively
      regulates CBF expression and freezing tolerance in plants.

PMID- 29056552
TI  - Hemodynamic Forces Sculpt Developing Heart Valves through a KLF2-WNT9B Paracrine
      Signaling Axis.
AB  - Hemodynamic forces play an essential epigenetic role in heart valve development,
      but how they do so is not known. Here, we show that the shear-responsive
      transcription factor KLF2 is required in endocardial cells to regulate the
      mesenchymal cell responses that remodel cardiac cushions to mature valves.
      Endocardial Klf2 deficiency results in defective valve formation associated with
      loss of Wnt9b expression and reduced canonical WNT signaling in neighboring
      mesenchymal cells, a phenotype reproduced by endocardial-specific loss of Wnt9b.
      Studies in zebrafish embryos reveal that wnt9b expression is similarly restricted
      to the endocardial cells overlying the developing heart valves and is dependent
      upon both hemodynamic shear forces and klf2a expression. These studies identify
      KLF2-WNT9B signaling as a conserved molecular mechanism by which fluid forces
      sensed by endothelial cells direct the complex cellular process of heart valve
      development and suggest that congenital valve defects may arise due to subtle
      defects in this mechanotransduction pathway.

PMID- 29056554
TI  - Development of a novel Schiff base derivative for enhancing the anticancer
      potential of 5-aminolevulinic acid-based photodynamic therapy.
AB  - 5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now
      widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA
      PDT) of various cancers. Recently, we found that treatment of cancer cells with
      the Schiff base derivative TX-816 along with ALA could significantly increase the
      efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to
      3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX
      816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT.
      Furthermore, DCSA could restore the sensitivity of cancer cells that acquired
      resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a
      potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might
      be a useful compound for designing prodrug-type ALA-PDT enhancers.

PMID- 29056555
TI  - The effect of ARC ablation on skeletal muscle morphology, function, and apoptotic
      signaling during aging.
AB  - Augmented apoptotic signaling can result in degradation of skeletal muscle
      proteins and loss of myonuclei, ultimately contributing to muscle atrophy and
      contractile dysfunction. Apoptosis repressor with caspase recruitment domain
      (ARC) is an anti-apoptotic protein highly expressed in skeletal muscle. Here we
      examined the role of ARC on age-related skeletal muscle apoptosis and wasting by
      utilizing an ARC-deficient mouse model. Aged mice displayed a number of
      morphological, phenotypic, and contractile alterations in both soleus and
      plantaris muscle with aging. Although no differences were found in proteolytic
      enzyme activity, ARC protein decreased while several anti-apoptotic proteins
      (e.g., BCL2, BCLXL, HSP70, and XIAP) and the release of mitochondrial housed
      protein (i.e., SMAC, AIF) increased in aged muscle. Importantly, ARC KO mice had
      low muscle weights and fewer fibers in soleus, with 2-year-old ARC KO mice
      displaying lower mitochondrial BCL2 protein along with augmented release of CYTC
      and SMAC in red/oxidative muscle. Overall, these results indicate that aged
      skeletal muscle undergoes atrophy as well as contractile and fiber type
      composition alterations despite an increase in anti-apoptotic protein expression.
      Although some mitochondrial-specific apoptotic alterations occurred in skeletal
      muscle due to ARC ablation over the lifespan, our data suggest that ARC may not
      have a large influence during skeletal muscle aging.

PMID- 29056557
TI  - AKAP150 involved in paclitaxel-induced neuropathic pain via inhibiting CN/NFAT2
      pathway and downregulating IL-4.
AB  - Antitubulin chemotherapeutics agents, such as paclitaxel, are effective
      chemotherapy drugs for cancer treatment. However, painful neuropathy is a major
      adverse effect limiting the wider application of chemotherapeutics. In this
      study, we found that A-kinase anchor protein 150 (AKAP150) was significantly
      upregulated after paclitaxel injection. Inhibition of AKAP150 via siRNA or
      AKAP150flox/flox in rodents alleviated the pain behavior induced by paclitaxel,
      and partly restored the decreased calcineurin (CN) phosphatase activity after
      paclitaxel treatment. Paclitaxel decreased the expression of anti-inflammatory
      cytokine interleukin-4 (IL-4), and intrathecal injections of IL-4 effectively
      alleviated paclitaxel-induced hypersensitivity and the frequency of dorsal root
      ganglion (DRG) neurons action potential. The decreased CN enzyme activity,
      resulted in reduced protein expression of nuclear factor of activated T cells 2
      (NFAT2) in cell nuclei. Chromatin immunoprecipitation showed that, NFAT2 binds to
      the IL-4 gene promoter regulating the protein expression of IL-4. Overexpression
      of NFAT2 by intrathecal injection of the AAV5-NFAT2-GFP virus alleviated the pain
      behavior induced by paclitaxel via increasing the expression of IL-4. Knocked
      down AKAP150 by siRNA or AAV5-Cre-GFP partly restored the expression of IL-4 in
      DRG. Our results indicated that regulation of IL-4 via the CN/NFAT2 pathway
      mediated by AKAP150 could be a pivotal treatment target for paclitaxel-induced
      neuropathic pain and or other neuropsychiatric disorders.

PMID- 29056556
TI  - Injectable iodine-125 labeled tissue marker for radioactive localization of non
      palpable breast lesions.
AB  - : We have developed a 125I-radiolabeled injectable fiducial tissue marker with
      the potential to replace current methods used for surgical guidance of non
      palpable breast tumors. Methods in routine clinical use today such as radioactive
      seed localization, radio-guided occult lesion localization and wire-guided
      localization suffers from limitations that this injectable fiducial tissue marker
      offers solutions to. The developed 125I-radiolabeled injectable fiducial tissue
      marker is based on highly viscous sucrose acetate isobutyrate. The marker was
      readily inserted in NMRI mice and proved to be spatially well-defined and stable
      over a seven day period with excellent CT contrast (>1500 HU), enabling
      fluoroscopic visualization of the marker during placement. The radioactivity
      remains strongly associated with the marker during the implantation period, which
      limits exposure to healthy tissue. Biodistribution studies show that there is
      negligible radioactivity in all non-tumor tissues sampled, with the exception of
      the thyroid gland, where limited accumulation was observed (0.06% of injected
      dose after 7 days). Based on the excellent performance of the marker and the fact
      that it can be delivered through thin hypodermic needles (>=27G), the marker
      holds great promise for clinical application, since patient discomfort is reduced
      significantly compared to current methods. STATEMENT OF SIGNIFICANCE: A new type
      of tissue marker for local administration to non-palpable breast tumors has been
      developed. The surgical guidance marker is based on derivatives of the
      biomaterial sucrose acetate isobutyrate and unlike currently used markers it is
      injectable in the tissue using thin needles, reducing the discomfort to the
      patients significantly. The marker confers CT contrast and has radioactive
      properties, meaning it also could find use in brachytherapy. The design of the
      iodine-125 labeled fiducial tissue marker enables control of dosimetry as well as
      a choice of iodine isotope used. The marker is anticipated to be clinical
      applicable due to its contrast performance in mice and its potential for enhanced
      flexibility in surgical procedures, compared to current methods.

PMID- 29056558
TI  - SPYRAL HTN-OFF MED study: Renal denervation in the spiral orbits of current
      results and future studies.

PMID- 29056559
TI  - Smoking impairs vagal modulation in old persons: the more we age, the more we
      learn.

PMID- 29056561
TI  - Bloom syndrome does not always present with sun-sensitive facial erythema.
AB  - Bloom syndrome is an autosomal recessive condition characterized by severe pre-
      and postnatal growth deficiency, immunodeficiency, an increased risk for
      malignancies, craniofacial dysmorphisms, and "typical" erythematous sun-sensitive
      skin lesions of the face. This facial rash has a butterfly-shaped distribution
      around the nose and is usually observed for the first time during the early years
      of life. Though reported as being a main feature of Bloom syndrome, there seems
      to be phenotypic variability regarding this facial skin rash among patients. It
      has been previously reported that in some individuals with Bloom syndrome these
      sun-sensitive lesions are less prominent or even absent. In this report we
      describe a 36 year old woman with short stature, microcephaly, several
      dysmorphisms, congenital hypothyroidism and premature ovarian failure. She was
      diagnosed with nasopharyngeal carcinoma at 36 years of age, only a few months
      after her consultation at the department of Clinical Genetics. Whole Exome
      Sequencing demonstrated that she had Bloom syndrome caused by a compound
      heterozygous mutation in BLM (c.2207_2212delinsTAGATTC; p.(Tyr736Leufs*5) and
      c.3681del; p.(Lys1227Asnfs*52)). She did not have facial sun-sensitive
      erythematous rash during childhood nor adulthood. We conclude that Bloom syndrome
      does not always present with erythematous sun-sensitive skin lesions of the face.
      We would like to underline that phenotypic variation regarding this "hallmark"
      feature of Bloom syndrome exists. Being aware of this might prevent a delay in
      diagnosing this rare short-stature syndrome and, subsequently, its potential
      clinical implications.

PMID- 29056562
TI  - Causes of Hospital Admissions in Domus: A Randomized Controlled Trial of
      Specialized Palliative Cancer Care at Home.
AB  - CONTEXT: Avoidable hospital admissions are important negative indicators of
      quality of end-of-life care. Specialized palliative care (SPC) may support
      patients remaining at home. OBJECTIVES: Therefore, the purpose of this study was
      to investigate if SPC at home could prevent hospital admissions in patients with
      incurable cancer. METHODS: These are secondary results of Domus: a randomized
      controlled trial of accelerated transition to SPC with psychological intervention
      at home (Clinicaltrials.gov: NCT01885637). Participants were patients with
      incurable cancer and limited antineoplastic treatment options and their
      caregivers. They were included from the Department of Oncology, Rigshospitalet,
      Denmark, between 2013 and 2016. The control group received usual care. Outcomes
      were hospital admissions, causes thereof, and patient and caregiver perceptions
      of place of care (home, hospital, etc.) at baseline, four weeks, eight weeks, and
      six months. RESULTS: During the study, 340 patients were randomized and 322 were
      included in modified intention-to-treat analyses. Overall, there were no
      significant differences in hospital admissions between the groups. The
      intervention group had more admissions triggered by worsened general health (22%
      vs. 16%, P = 0.0436) or unmanageable home situation (8% vs. 4%, P = 0.0119).
      After diagnostics, admissions were more often caused by clinical symptoms of
      cancer without progression in the intervention group (11% vs. 7%, P = 0.0493).
      The two groups did not differ significantly in overall potentially avoidable
      admissions. Both groups felt mostly safe about their place of care. CONCLUSION:
      The intervention did not prevent hospital admissions. Likely, any intervention
      effects were outweighed by increased identification of problems in the
      intervention group leading to hospital admissions. Overall, patients and
      caregivers felt safe in their current place of care.

PMID- 29056563
TI  - Impact of Targeted Therapy on the Quality of End-of-Life Care for Patients With
      Non-Small-Cell Lung Cancer: A Population-Based Study in Taiwan.
AB  - CONTEXT: Targeted therapies with epidermal growth factor receptor tyrosine kinase
      inhibitors have been widely used in the treatment of advanced non-small-cell lung
      cancer (NSCLC). However, little research has focused on the use of targeted
      therapies at the end of life (EOL). OBJECTIVES: This study investigated the
      determinants of receiving targeted therapy during the last month of life and how
      targeted therapies affect the quality of EOL care. METHODS: We conducted a
      retrospective population-based study using a cancer registry and National Health
      Insurance claims data among 42,678 Taiwanese NSCLC decedents in 2005-2012.
      Propensity score matching and generalized linear mixed models were used to
      estimate associations. RESULTS: We identified 3439 (21.3%) NSCLC patients who
      received targeted therapy within 30 days of death. Younger age, adenocarcinoma
      histology, postdiagnosis survival exceeding six months, and later year of death
      were associated with receiving targeted agents at EOL. The odds increased when
      patients were treated by pulmonologists or oncologists or in district hospitals
      or facilities with a higher case volume. Patients who were prescribed targeted
      therapy near death were significantly more likely to undergo aggressive EOL care
      (odds ratio = 2.35, 95% CI = 1.83-3.02) including multiple emergency department
      visits, hospitalization exceeding 14 days, admission to intensive care units, use
      of intubation and mechanical ventilation, cardiopulmonary resuscitation, and late
      hospice referrals. CONCLUSIONS: Targeted therapy at EOL should be considered a
      quality-of-care indicator. Guidance in the cessation of targeted therapy and the
      ongoing monitoring of practice initiatives are warranted. The decision-making
      processes associated with EOL care also require further investigation.

PMID- 29056560
TI  - Membrane biology visualized in nanometer-sized discs formed by styrene maleic
      acid polymers.
AB  - Discovering how membrane proteins recognize signals and passage molecules remains
      challenging. Life depends on compartmentalizing these processes into dynamic
      lipid bilayers that are technically difficult to work with. Several polymers have
      proven adept at separating the responsible machines intact for detailed analysis
      of their structures and interactions. Styrene maleic acid (SMA) co-polymers
      efficiently solubilize membranes into native nanodiscs and, unlike amphipols and
      membrane scaffold proteins, require no potentially destabilizing detergents. Here
      we review progress with the SMA lipid particle (SMALP) system and its impacts
      including three dimensional structures and biochemical functions of peripheral
      and transmembrane proteins. Polymers systems are emerging to tackle the remaining
      challenges for wider use and future applications including in membrane
      proteomics, structural biology of transient or unstable states, and discovery of
      ligand and drug-like molecules specific for native lipid-bound states.

PMID- 29056564
TI  - A Nationwide Survey About Palliative Sedation Involving Japanese Palliative Care
      Specialists: Intentions and Key Factors Used to Determine Sedation as
      Proportionally Appropriate.
AB  - CONTEXT: Although there has long been debate about physicians' intentions and
      what physicians consider to be proportionally appropriate when performing
      palliative sedation, few large studies have been performed. OBJECTIVES: To
      identify physicians' intentions when starting continuous deep sedation and to
      clarify what factors determine whether physicians regard sedation as
      proportionally appropriate in relation to expected survival, the patients'
      wishes, and refractoriness. METHODS: A nationwide questionnaire survey of
      Japanese palliative care specialists was performed from August to December 2016.
      We defined continuous deep sedation as the continuous use of sedatives to relieve
      intolerable and refractory symptoms with the loss of consciousness until death.
      RESULTS: Of the 695 palliative care specialists enrolled, 440 were analyzed
      (response rate, 69%). A total of 95% and 87% of the physicians reported that they
      explicitly intended to perform symptom palliation and decrease consciousness
      levels, respectively. Moreover, 38% answered that they explicitly intended to
      maintain unconsciousness until death, and 11% reported that they intended to
      shorten survival to some extent. The respondents considered that continuous deep
      sedation is more appropriate when the predicted survival is shorter, the
      patients' wishes are consistent and clear, and confidence in the refractoriness
      of symptoms is higher. CONCLUSIONS: Japanese palliative care specialists
      explicitly intend to control symptoms and reduce the level of consciousness when
      performing continuous deep sedation, but there are differences in their
      intentions with regard to maintaining unconsciousness until death. Predicted
      survival, patients' wishes, and confidence in refractoriness are associated with
      physicians' judgment that sedation is proportionally appropriate.

PMID- 29056565
TI  - Risk factors and pharmacologic prophylaxis for venous thromboembolism in elective
      spine surgery.
AB  - BACKGROUND CONTEXT: Venous thromboembolism (VTE) is a known complication after
      spine surgery, but prophylaxis guidelines are ambiguous for patients undergoing
      elective spine surgery. PURPOSE: The objective of this study was to characterize
      the incidence and risk factors for VTE and the association of pharmacologic
      prophylaxis with VTE and bleeding complications after elective spine surgery.
      STUDY DESIGN/SETTING: This is a retrospective cohort study of patients undergoing
      elective spine surgery in the National Surgical Quality Improvement Program
      (NSQIP) database and a retrospective cohort analysis at an academic medical
      center. PATIENT SAMPLE: This study included 109,609 patients in the NSQIP
      database from 2005 to 2014 and 2,855 patients at the authors' institution from
      January 2013 to March 2016 who underwent elective spine surgery. OUTCOME
      MEASURES: The incidence and risk factors for VTE were assessed in both cohorts
      based on the NSQIP criteria. The incidence of bleeding complications requiring
      reoperation was assessed based on operative reports in the institutional cohort.
      MATERIALS AND METHODS: Associations of patient and procedure factors with VTE
      were characterized in the NSQIP population. In the single-institution cohort, in
      addition to NSQIP variables, a chart review was completed to determine the use of
      VTE prophylaxis, the history of prior VTE, and the incidence of hematoma
      requiring reoperation. The association of patient and procedure variables,
      including pharmacologic prophylaxis and history of prior VTE, with VTE and
      hematoma requiring reoperation were determined with multivariate regression.
      RESULTS: Among 109,609 elective spine surgery patients in NSQIP, independent risk
      factors for VTE were greater age, male gender, increasing body mass index,
      dependent functional status, lumbar spine surgery, longer operative time,
      perioperative blood transfusion, longer length of stay, and other postoperative
      complications. There were 2,855 patients included in the institutional cohort.
      Pharmacologic prophylaxis was performed in 56.3% of the institutional patients,
      of whom 97.1% received unfractionated heparin. When controlling for patient and
      procedural variables, pharmacologic prophylaxis did not significantly influence
      the rate of VTE, but was associated with a significant increase in hematoma
      requiring a return to the operating room (relative risk=7.37, p=.048).
      CONCLUSIONS: Pharmacologic prophylaxis, primarily with unfractionated heparin,
      after elective spine surgery was not associated with a significant reduction in
      VTE. However, there was a significant increase in postoperative hematoma
      requiring reoperation among patients undergoing prophylaxis. This raises
      questions about the routine use of unfractionated heparin for VTE prophylaxis and
      supports the need for further consideration of risks and benefits of
      chemoprophylaxis after elective spine surgery.

PMID- 29056566
TI  - A reliability and validity study for different coronal angles using ultrasound
      imaging in adolescent idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: Radiation exposure remains a big concern in adolescent
      idiopathic scoliosis (AIS). Ultrasound imaging of the spine could significantly
      reduce or possibly even eliminate this radiation hazard. The spinous processes
      (SPs) and transverse processes (TPs) were used to measure the coronal deformity.
      Both landmarks provided reliable information on the severity of the curve as
      related to the traditional Cobb angle. However, it remained unclear which coronal
      ultrasound angle is the most appropriate method to measure the curve severity.
      PURPOSE: The objective of this study was to test the reliability and the validity
      of several ultrasound angle measurements in the coronal plane as compared with
      the radiographic coronal Cobb angle in patients with AIS. STUDY DESIGN/SETTING:
      This is a cross-sectional study. PATIENT SAMPLE: The study included 33 patients
      with AIS, both male and female (Cobb angle range: 3 degrees -90 degrees , primary
      and secondary curves), who underwent posterior-anterior radiography of the spine.
      OUTCOME MEASURES: The outcome measures were the reliability (intraclass
      correlation coefficients [ICCs] for the intra- and interobserver variabilities)
      and the validity (linear regression analysis and Bland-Altman method, including
      the mean absolute difference [MAD]) of different ultrasound measurements.
      MATERIALS AND METHODS: The patients were scanned using a dedicated ultrasound
      machine (Scolioscan, Telefield Medical Imaging Ltd, Hong Kong). The reliability
      and the validity were tested for three coronal ultrasound angles: an automatic
      and manual SP angle and a manual TP angle as compared with the radiographic
      coronal main thoracic or (thoraco)lumbar Cobb angles. RESULTS: The ICC showed
      very reliable measurements of all ultrasound methods (ICC >=0.84). The ultrasound
      angles were 15%-37% smaller as compared with the Cobb angles; however, excellent
      linear correlations were seen between all ultrasound angles and the Cobb angle
      (thoracic: R2>=0.987 and (thoraco)lumbar R2>=0.970), and the Bland-Altman plot
      showed a good agreement between all ultrasound angles and the Cobb angle. The
      MADs of the ultrasound angles, corrected using the linear regression equation,
      and the Cobb angles showed no significant difference between the different
      ultrasound angles (MAD: automatic SP angle 4.9 degrees +/-3.2 degrees , manual SP
      angle 4.5 degrees +/-3.1 degrees , and manual TP angle 4.7 degrees +/-3.6 degrees
      ; p>=.388). CONCLUSIONS: Coronal ultrasound angles are based on different
      landmarks than the traditional Cobb angle measurement and cannot represent the
      same angle values. In this study, we found excellent correlations between the
      ultrasound and Cobb measurements, without differences in the reliability and
      validity between the ultrasound angles based on the SPs and TPs. Therefore, the
      severity of the deformity in patients with AIS can be assessed by ultrasound
      imaging, avoiding hazardous ionizing radiation and enabling more individualized
      patient care. It also opens possibilities for screening.

PMID- 29056567
TI  - Molecular forms of C-type natriuretic peptide in cerebrospinal fluid and plasma
      reflect differential processing in brain and pituitary tissues.
AB  - C-type natriuretic peptide (CNP) is a paracrine growth factor widely expressed
      within tissues of the central nervous system. Consistent with this is the high
      concentration of CNP in cerebrospinal fluid (CSF), exceeding levels in the
      systemic circulation. CNP abundance is high in hypothalamus and especially
      enriched in pituitary tissue where - in contrast to hypothalamus - processing to
      CNP-22 is minimal. Recently we have shown that dexamethasone acutely raises CNP
      peptides throughout the brain as well as in CSF and plasma. Postulating that
      molecular forms of CNP would differ in central tissues compared to forms in
      pituitary and plasma, we have characterized the molecular forms of CNP in tissues
      (hypothalamus, anterior and posterior pituitary gland) and associated fluids (CSF
      and plasma) using size-exclusion high performance liquid chromatography (SE-HPLC)
      and radioimmunoassay in control (saline-treated) and dexamethasone-treated adult
      sheep. Three immunoreactive-CNP components were identified which were consistent
      with proCNP (1-103), CNP-53 and CNP-22, but the presence and proportions of these
      different fragments differed among tissues. Peaks consistent with CNP-53 were the
      dominant form in all tissues and fluids. Peaks consistent with proCNP,
      conspicuous in hypothalamic extracts, were negligible in CSF whereas proportions
      of low molecular weight immunoreactivity (IR) consistent with CNP-22 were similar
      in hypothalamus, posterior pituitary gland and CSF. In contrast, in both plasma
      and the anterior pituitary gland, proportions of higher molecular weight IR,
      consistent with CNP-53 and proCNP, predominated, and low molecular weight IR
      consistent with CNP-22 was very low. After dexamethasone, proCNP like material -
      but not other forms - was increased in all samples except CSF, consistent with
      increased synthesis and secretion. In conclusion, immunoreactive forms of CNP in
      central tissues differ from those identified in anterior pituitary tissue and
      plasma - suggesting that the anterior pituitary gland may contribute to systemic
      levels of CNP in some physiological settings.

PMID- 29056568
TI  - Anatomic and Functional Outcomes of Paramesonephric Remnant-Supported
      Laparoscopic Double-Layer Peritoneal Pull-Down Vaginoplasty Technique in Patients
      with Mayer-Rokitansky-Kuster-Hauser Syndrome: Uncu Modification.
AB  - OBJECTIVE: To describe modifications to the double-layer peritoneal pull-down
      laparoscopic vaginoplasty technique (Davydov operation) and evaluate anatomic and
      functional outcomes of the new technique, known as the Uncu modification. DESIGN:
      Case series (Canadian Task Force classification III). SETTING: Tertiary care
      university hospital. PATIENTS: Women with Mayer-Rokitansky-Kuster-Hauser syndrome
      (MRKHS) who underwent surgery between 2010 and 2016. INTERVENTIONS: Laparoscopic
      double-layer peritoneal pull-down vaginoplasty with paramesonephric remnant
      support to the neovagina. MEASUREMENTS AND MAIN RESULTS: Long-term anatomic and
      functional satisfaction results. Twenty-seven women with MRKHS underwent surgery
      with the Uncu-modified Davydov procedure. At 1 year after surgery, the mean
      vaginal length in these patients was 7.91 +/- 1.4 cm. Among the 23 patients who
      had regular vaginal intercourse, the mean functional satisfaction score was 8.65
      +/- 1.2. One patient had a perioperative bladder injury, and another patient had
      a rectovaginal fistula at 3 months after the operation. One woman who did not
      comply with the prescribed postoperative mold exercises had complete closure of
      the introitus. CONCLUSION: The Uncu modified laparoscopic double-layer peritoneal
      pull-down technique appears to be an effective and safe surgical management
      option that is easy to learn and perform by gynecologic surgeons.

PMID- 29056569
TI  - AZD3759 for CNS metastases in EGFR-mutant lung cancer.

PMID- 29056571
TI  - In control of ambient and household air pollution - how low should we go?

PMID- 29056570
TI  - Activity and safety of AZD3759 in EGFR-mutant non-small-cell lung cancer with CNS
      metastases (BLOOM): a phase 1, open-label, dose-escalation and dose-expansion
      study.
AB  - BACKGROUND: CNS metastases-including brain and leptomeningeal metastases-from
      epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC)
      are associated with poor prognosis. AZD3759 is a novel EGFR tyrosine kinase
      inhibitor with high capability to penetrate the blood-brain barrier. We aimed to
      assess the safety, tolerability, pharmacokinetics, and efficacy of AZD3759 in
      patients with EGFR-mutant NSCLC with brain and leptomeningeal metastases.
      METHODS: This open-label, multicentre, phase 1 study was undertaken at 11 centres
      and hospitals in Australia, South Korea, Taiwan, and the USA. Eligible patients
      included those with histologically confirmed, advanced-stage, EGFR-mutant NSCLC.
      The study was done in two parts, with dose-escalation and dose-expansion phases.
      In the dose-escalation phase, patients who had progressed after treatment with an
      EGFR tyrosine kinase inhibitor received AZD3759 at 50 mg, 100 mg, 200 mg, 300 mg,
      or 500 mg twice a day. In the dose-expansion phase, AZD3759 at 200 mg or 300 mg
      twice a day was administered to patients with either brain or leptomeningeal
      metastases who had never received an EGFR tyrosine kinase inhibitor and patients
      with leptomeningeal metastases who had been pretreated with an EGFR tyrosine
      kinase inhibitor. The primary objective was safety and tolerability, with
      severity of adverse events assessed with the National Cancer Institute's Common
      Terminology Criteria for Adverse Events, version 4.03. This trial is registered
      with ClinicalTrials.gov, number NCT02228369. FINDINGS: Between Nov 18, 2014, and
      Sept 7, 2016, 67 patients with NSCLC were enrolled into the study, 29 to the dose
      escalation phase and 38 to the dose-expansion phase. At data cutoff (Dec 12,
      2016), three (10%) patients in the dose-escalation phase and 20 (53%) in the dose
      expansion phase were still receiving treatment. Dose-limiting toxic effects
      occurred in two (67%) of three patients who received 500 mg twice a day in the
      dose-escalation phase (grade 3 acne [n=1] and intolerable grade 2 mucosal
      inflammation [n=1]); hence, doses of 200 mg and 300 mg twice a day were selected
      for further assessment in the dose-expansion phase. Drug-related skin and
      gastrointestinal disorders of any grade occurred in 35 (92%) and 29 (76%)
      patients in the dose-expansion phase, respectively, and led to treatment
      discontinuation in one (4%) patient treated with 200 mg twice a day (grade 3
      increase of alanine aminotransferase and aspartate aminotransferase) and two
      (13%) patients given 300 mg twice a day (grade 3 diarrhoea [n=1] and grade 3 skin
      rash [n=1]). Grade 3 skin and gastrointestinal disorders occurred in four (17%)
      and two (9%) patients, respectively, at a dose of 200 mg twice a day, and in six
      (40%) and four (27%) patients, respectively, at a dose of 300 mg twice a day. No
      grade 4 disorders arose. Other grade 3 disorders included hepatobiliary and renal
      disorders (three [13%] at 200 mg twice a day), asthenia (one [7%] at 300 mg twice
      a day), infections and infestations (one [7%] at 300 mg twice a day), and
      metabolism and nutrition disorders (one [4%] at 200 mg twice a day and one [7%]
      at 300 mg twice a day). INTERPRETATION: AZD3759 at a dose of 200 mg twice daily
      showed a tolerable safety profile in patients with NSCLC and CNS metastases who
      had either never received a tyrosine kinase inhibitor or who had been pretreated
      with a tyrosine kinase inhibitor. The good penetration of the blood-brain barrier
      by AZD3759, and its promising clinical activity, support further assessment of
      this compound in studies. FUNDING: AstraZeneca.

PMID- 29056572
TI  - Egypt's respiratory health in focus.

PMID- 29056573
TI  - Noncoding RNA Expression and Targeted Next-Generation Sequencing Distinguish
      Tubulocystic Renal Cell Carcinoma (TC-RCC) from Other Renal Neoplasms.
AB  - Tubulocystic renal cell carcinoma (TC-RCC) is a rare recently described renal
      neoplasm characterized by gross, microscopic, and immunohistochemical differences
      from other renal tumor types and was recently classified as a distinct entity.
      However, this distinction remains controversial particularly because some genetic
      studies suggest a close relationship with papillary RCC (PRCC). The molecular
      basis of this disease remains largely unexplored. We therefore performed
      noncoding (nc) RNA/miRNA expression analysis and targeted next-generation
      sequencing mutational profiling on 13 TC-RCC cases (11 pure, two mixed TC
      RCC/PRCC) and compared with other renal neoplasms. The expression profile of
      miRNAs and other ncRNAs in TC-RCC was distinct and validated 10 differentially
      expressed miRNAs by quantitative RT-PCR, including miR-155 and miR-34a, that were
      significantly down-regulated compared with PRCC cases (n = 22). With the use of
      targeted next-generation sequencing we identified mutations in 14 different
      genes, most frequently (>60% of TC-RCC cases) in ABL1 and PDFGRA genes. These
      mutations were present in <5% of clear cell RCC, PRCC, or chromophobe RCC cases
      (n > 600) of The Cancer Genome Atlas database. In summary, this study is by far
      the largest molecular study of TC-RCC cases and the first to investigate either
      ncRNA expression or their genomic profile. These results add molecular evidence
      that TC-RCC is indeed a distinct entity from PRCC and other renal neoplasms.

PMID- 29056575
TI  - Identification of Enteric Viruses in Oral Swabs from Children with Acute
      Gastroenteritis.
AB  - Stool is the diagnostic specimen of choice to identify enteropathogens in
      pediatric gastroenteritis. However, stool collection is challenging and its
      diagnostic characteristics in patients with isolated vomiting are unknown.
      Therefore, we evaluated if oral swabs are a suitable alternative specimen to
      stools. In total, 738 oral swabs and 577 stool specimens were collected from 738
      children with vomiting and/or diarrhea. All specimens were tested by a laboratory
      developed quantitative RT-PCR Gastroenteritis Virus Panel; 150 oral swabs and 577
      stool specimens were tested by the commercial gastroenteritis pathogen panel. The
      Gastroenteritis Virus Panel identified adenovirus (n = 38), norovirus (n = 21),
      and rotavirus (n = 16) commonly in oral swabs. In stool specimens, rotavirus (n =
      139), norovirus (n = 86), and adenovirus (n = 69) were detected commonly.
      Compared with stool specimens, the specificity of oral swabs was 99% (95% CI, 96%
      100%); the sensitivity of oral swabs was 18% (95% CI, 14%-22%) for the detection
      of enteric viruses. The Gastrointestinal Pathogen Panel identified enteric
      bacteria and parasites in stool but not in oral swabs. Given the lower
      sensitivity of oral swabs, stool remains a preferable specimen to detect enteric
      viruses. However, with their high specificity, oral swabs can be considered as a
      suitable specimen if stool specimens are unavailable. Nevertheless, negative oral
      swabs require a confirmative test of stool specimens.

PMID- 29056574
TI  - Plasmodium Detection and Differentiation by Direct-on-Blood PCR Nucleic Acid
      Lateral Flow Immunoassay: Development, Validation, and Evaluation.
AB  - Decreasing malaria transmission warrants the search for highly sensitive point-of
      care diagnostics, especially in resource-limited settings. The direct-on-blood
      PCR nucleic acid lateral flow immunoassay (db-PCR-NALFIA) is a simplified PCR
      based technique with a lateral flow readout that does not require sample
      preparation. Two duplex db-PCR-NALFIAs were developed: a pan
      Plasmodium/Plasmodium falciparum (pan/P. falciparum) and a pan
      Plasmodium/Plasmodium vivax (pan/P. vivax) assay. Confirmed positive samples (n =
      61) and negative controls (n = 40) were used for laboratory validations. A
      prospective field evaluation of the pan/P. falciparum assay was performed in
      Kenya (n = 300). In the laboratory validation, sensitivity and specificity of the
      pan/P. falciparum assay were 100% (95% CI, 94.1%-100%) and 100% (95% CI, 91.2%
      100%), respectively. Sensitivity and specificity of the pan/P. vivax assay were
      100% (95% CI, 94.1%-100%) and 97.5% (95% CI, 86.8%-99.9%), respectively. In
      Kenya, sensitivity of the pan/P. falciparum db-PCR-NALFIA was 97.2% (95% CI,
      93.0%-99.2%) and specificity was 74.2% (95% CI, 67.0%-81.0%) compared with
      reference standard microscopy. When using real-time quantitative PCR as a
      reference standard, sensitivity was 84.5% (95% CI, 78.7%-89.3%) and specificity
      was 85.4% (95% CI, 77.1%-91.6%). Db-PCR-NALFIA is a sensitive, specific, and easy
      method for the detection and species differentiation of Plasmodium. This test is
      especially of interest for malaria control or elimination programs in low
      transmission settings that require accurate detection of low parasite densities.

PMID- 29056577
TI  - Is Neurogenic Bladder a Risk Factor for Febrile Urinary Tract Infection After
      Ureteroscopy and, if so, Why?
AB  - OBJECTIVE: To characterize the rate of febrile urinary tract infections (UTIs)
      after ureteroscopy in patients with neurogenic bladder compared with those with
      physiologically normal bladders. Although generally considered safe and
      effective, there is a growing body of evidence suggesting that patients with
      neurogenic bladder are at an increased risk of infectious complications following
      ureteroscopy. METHODS: We performed a retrospective chart review of those
      undergoing ureteroscopy in a single academically affiliated hospital system
      between June 2013 and May 2016. Information regarding neurogenic bladder status,
      culture results, bladder management, and the presence of upper tract
      decompression was collected. Postoperative febrile UTI was defined as a hospital
      admission within 1 week of surgery because of fever not attributable to another
      source. RESULTS: Of 467 ureteroscopies, 44 (9.5%) were performed in the setting
      of neurogenic bladder. Febrile UTI rates were higher in patients with neurogenic
      bladder compared with control patients (9% vs 1.4%, P = .01) with significantly
      higher rates in those dependent on bladder catheterization. Interestingly, the
      presence of a nephrostomy tube in patients with physiologically normal bladders
      increased the risk of postoperative febrile UTI to levels comparable with
      patients with neurogenic bladder who were catheter dependent (10.5% vs 12.5%,
      respectively). CONCLUSION: Although infectious complications in the neurogenic
      population are likely multifactorial, the reliance on catheterization and thus
      colonization appears to be a significant factor and extends to non-neurogenic
      patients. These data suggest that bacterial colonization may be the significant
      underlying risk factor for febrile UTI after ureteroscopy.

PMID- 29056576
TI  - Development of a Patient-specific Tumor Mold Using Magnetic Resonance Imaging and
      3-Dimensional Printing Technology for Targeted Tissue Procurement and Radiomics
      Analysis of Renal Masses.
AB  - OBJECTIVE: To implement a platform for colocalization of in vivo quantitative
      multiparametric magnetic resonance imaging features with ex vivo surgical
      specimens of patients with renal masses using patient-specific 3-dimensional (3D)
      printed tumor molds, which may aid in targeted tissue procurement and radiomics
      and radiogenomic analyses. MATERIALS AND METHODS: Volumetric segmentation of 6
      renal masses was performed with 3D Slicer (http://www.slicer.org) to create a 3D
      tumor model. A slicing guide template was created with specialized software,
      which included notches corresponding to the anatomic locations of the magnetic
      resonance images. The tumor model was subtracted from the slicing guide to create
      a depression in the slicing guide corresponding to the exact size and shape of
      the tumor. A customized, tumor-specific, slicing guide was then printed using a
      3D printer. After partial nephrectomy, the surgical specimen was bivalved through
      the preselected magnetic resonance imaging (MRI) plane. A thick slab of the tumor
      was obtained, fixed, and processed as a whole-mount slide and was correlated to
      multiparametric MRI findings. RESULTS: All patients successfully underwent
      partial nephrectomy and adequate fitting of the tumor specimens within the 3D
      mold was achieved in all tumors. Distinct in vivo MRI features corresponded to
      unique pathologic characteristics in the same tumor. The average cost of printing
      each mold was US$160.7 +/- 111.1 (range: US$20.9-$350.7). CONCLUSION: MRI-based
      preoperative 3D printing of tumor-specific molds allow for accurate sectioning of
      the tumor after surgical resection and colocalization of in vivo imaging features
      with tissue-based analysis in radiomics and radiogenomic studies.

PMID- 29056578
TI  - Treatment for Vas Deferens Obstruction Following Childhood Herniorrhaphy.
AB  - OBJECTIVE: To enhance the management of inguinal obstruction, and to present the
      procedures and results of our surgical strategy for vas deferens obstruction
      following childhood herniorrhaphy. METHODS: We treated a total of 56 patients
      diagnosed with obstructive azoospermia following bilateral inguinal
      herniorrhaphy. First, conventional inguinal open surgery was performed. If the
      abdominal vas was not identified in the inguinal region, laparoscopy was used to
      retrieve the deeper abdominal vas deferens, which was obstructed above the
      internal inguinal ring. Then, microsurgical vasovasostomy (VV) was performed.
      Overall patency and natural pregnancy rates were determined. RESULTS: We
      terminated the surgery in 16 patients with pasty vasal fluid and no sperm. When
      bilateral remnants of the vas deferens were found, laparoscopic mobilization was
      not required, and 22 (55.0%) patients underwent bilateral VV with patency and
      natural pregnancy rates of 90.9% (20 of 22) and 50.0% (11 of 22), respectively.
      When a unilateral end could not be found, 7 (17.5%) patients underwent unilateral
      laparoscopy-assisted VV plus unilateral VV, with patency and natural pregnancy
      rates of 85.7% (6 of 7) and 42.9% (3 of 7), respectively. When bilateral ends
      were not found, 11 (27.5%) patients underwent bilateral laparoscopy-assisted VV,
      with patency and natural pregnancy rates of 81.8% (9 of 11) and 27.3% (3 of 11),
      respectively. Overall, our surgery yielded a patency rate of 87.5% (35 of 40) and
      a natural pregnancy rate of 42.5% (17 of 40). CONCLUSION: Our treatment for vas
      deferens obstruction following childhood herniorrhaphy yielded good postoperative
      outcomes in terms of sperm concentration and motility, vas patency, and natural
      pregnancy, with no complications.

PMID- 29056579
TI  - State-by-state Variation in Prostate-specific Antigen Screening Trends Following
      the 2011 United States Preventive Services Task Force Panel Update.
AB  - OBJECTIVE: To evaluate state-by-state trends in prostate-specific antigen (PSA)
      screening prevalence after the 2011 United States Preventive Services Task Force
      (USPSTF) recommendation against this practice. METHODS: We included 222,475 men
      who responded to the Behavioral Risk Factor Surveillance System 2012 and 2014
      surveys, corresponding to early and late post-USPSTF populations. Logistic
      regression was used to identify predictors of PSA screening and to calculate the
      adjusted and weighted state-by-state PSA screening prevalence and respective
      relative percent changes between 2012 and 2014. To account for unmeasured
      factors, the correlation between changes in PSA screening over time and changes
      in screening for colorectal and breast cancer were assessed. All analyses were
      conducted in 2016. RESULTS: Overall, 38.9% (95% confidence interval [CI] = 38.6%
      39.2%) reported receiving PSA screening in 2012 vs 35.8% (95% CI = 35.1%-36.2%)
      in 2014. State of residence, age, race, education, income, insurance, access to
      care, marital status, and smoking status were independent predictors of PSA
      screening in both years (all P <.001). In adjusted analyses, the nationwide PSA
      screening prevalence decreased by a relative 8.5% (95% CI = 6.4%-10.5%; P <.001)
      between 2012 and 2014. There was a vast state-by-state heterogeneity, ranging
      from a relative 26.6% decrease in Vermont to 10.2% increase in Hawaii. Overall,
      81.5% and 84.0% of the observed changes were not accompanied by matching changes
      in respective colorectal and breast cancer screening utilization, for which there
      were no updates in USPSTF recommendations. CONCLUSION: There is a significant
      state-by-state variation in PSA screening trends following the 2011 USPSTF
      recommendation. Further research is needed to elucidate the reasons for this
      heterogeneity in screening behavior among the states.

PMID- 29056580
TI  - Role of the Crumbs proteins in ciliogenesis, cell migration and actin
      organization.
AB  - Epithelial cell organization relies on a set of proteins that interact in an
      intricate way and which are called polarity complexes. These complexes are
      involved in the determination of the apico-basal axis and in the positioning and
      stability of the cell-cell junctions called adherens junctions at the apico
      lateral border in invertebrates. Among the polarity complexes, two are present at
      the apical side of epithelial cells. These are the Par complex including aPKC,
      PAR3 and PAR6 and the Crumbs complex including, CRUMBS, PALS1 and PATJ/MUPP1.
      These two complexes interact directly and in addition to their already well
      described functions, they play a role in other cellular processes such as
      ciliogenesis and polarized cell migration. In this review, we will focus on these
      aspects that involve the apical Crumbs polarity complex and its relation with the
      cortical actin cytoskeleton which might provide a more comprehensive hypothesis
      to explain the many facets of Crumbs cell and tissue properties.

PMID- 29056581
TI  - Objections still fail: a response to Faria.
AB  - In her reply to my critical assessment of objections to the Weatherall report's
      justification of non-human primate (NHP) research, Catia Faria focuses on three
      objections which she entitles 'the disanalogy', 'the utilitarian calculus' and
      'species overlap'. Faria finds my assessment unconvincing, butI argue that the
      objections still fail.

PMID- 29056582
TI  - 'Absolutely not!' Contextual values and equality of voices in mental health.

PMID- 29056583
TI  - Law and the perils of philosophical grafts.

PMID- 29056584
TI  - The 'French exception': the right to continuous deep sedation at the end of life.
AB  - In 2016, a law came into force in France granting terminally ill patients the
      right to continuous deep sedation (CDS) until death. This right was proposed as
      an alternative to euthanasia and presented as the 'French response' to problems
      at the end of life. The law draws a distinction between CDS and euthanasia and
      other forms of sympton control at the end of life. France is the first country in
      the world to legislate on CDS . This short report describes the particular
      context and underlying social values that led to this piece of legislation, and
      explores its meaning in the wider French context.

PMID- 29056585
TI  - Fall-related mortality in southern Sweden: a multiple cause of death analysis,
      1998-2014.
AB  - OBJECTIVES: To investigate temporal trend in fall mortality among adults (aged
      >=20 years) in southern Sweden using multiple cause of death data. METHODS: We
      examined all death certificates (DCs, n=2 01 488) in adults recorded in the Skane
      region during 1998-2014. We identified all fall deaths using International
      Statistical Classification of Diseases (ICD)-10 codes (W00-W19) and calculated
      the mortality rates by age and sex. Temporal trends were evaluated using
      joinpoint regression and associated causes were identified by age-adjusted and
      sex-adjusted observed/expected ratios. RESULTS: Falls were mentioned on 1.0% and
      selected as underlying cause in 0.7% of all DCs, with the highest frequency among
      those aged >=70 years. The majority (75.6%) of fall deaths were coded as
      unspecified fall (ICD-10 code: W19) followed by falling on or from stairs/steps
      (7.7%, ICD-10 code: W10) and other falls on the same level (6.3%, ICD-10 code:
      W18). The mean age at fall deaths increased from 77.5 years in 1998-2002 to 82.9
      years in 2010-2014 while for other deaths it increased from 78.5 to 79.8 years
      over the same period. The overall mean age-standardised rate of fall mortality
      was 8.3 and 4.0 per 1 00 000 person-years in men and women, respectively, and
      increased by 1.7% per year in men and 0.8% per year in women during 1998-2014.
      Head injury and diseases of the circulatory system were recorded as contributing
      cause on 48.7% of fall deaths. CONCLUSIONS: There is an increasing trend of
      deaths due to falls in southern Sweden. Further investigations are required to
      explain this observation particularly among elderly men.

PMID- 29056586
TI  - Epidemiology of paediatric trauma presenting to US emergency departments: 2006
      2012.
AB  - BACKGROUND: Traumatic injury is the leading cause of paediatric morbidity and
      mortality in the USA. We present updated national data on emergency department
      (ED) discharges for traumatic injury for a recent 7-year period. METHODS: We
      conducted a descriptive epidemiological analysis of the Nationwide Emergency
      Department Sample Survey, the largest and most comprehensive database in the USA,
      for 2006-2012. Among children and adolescents, we tracked changes in injury
      mechanism and severity, cost of care, injury intent and the role of trauma
      centres. RESULTS: There was an 8.3% (95% CI 7.7 to 8.9) decrease in the annual
      number of ED visits for traumatic injury in children and adolescents over the
      study period, from 8 557 904 (SE=5861) in 2006 to 7 846 912 (SE=5191) in 2012.
      The case-fatality rate was 0.04% for all injuries and 3.2% for severely injured
      children. Children and adolescents with high-mortality injury mechanisms were
      more than three times more likely to be treated at a level 1 trauma centre
      (OR=3.5, 95% CI 3.3 to 3.7), but were more no more likely to die (OR=0.96, 95% CI
      0.93 to 1.00). Traumatic brain injury diagnoses increased 22.2% (95% CI 20.6 to
      23.9) during the study period. Intentional assault accounted for 3% (SE=0.1) of
      all child and adolescent ED injury discharges and 7.2% (SE=0.3) of discharges
      among 15-19 year-olds. There was an 11.3% (95% CI 10.0 to 12.6) decline in motor
      vehicle injuries from 2009 to 2012. The total cost of care was $23 billion
      (SE=0.01), a 78% increase from 2006 to 2012. CONCLUSIONS: This analysis presents
      a recent portrait of paediatric trauma across the USA. These analyses indicate
      the important role and value of trauma centre care for injured children and
      adolescents, and that the most common causes and mechanisms of injury are
      preventable.

PMID- 29056587
TI  - Chronic widespread pain and increased mortality: biopsychosocial
      interconnections.

PMID- 29056589
TI  - Cerebral palsy in under 25 s: assessment and management (NICE Guideline NG62).

PMID- 29056590
TI  - Non-attendance at hospital appointments is poorly communicated to general
      practice, despite links with deprivation and safeguarding concerns.

PMID- 29056591
TI  - Puzzling pyramids.

PMID- 29056592
TI  - A shared data approach more accurately represents the rates and patterns of
      violence with injury assaults.
AB  - BACKGROUND: To investigate whether sharing and linking routinely collected
      violence data across health and criminal justice systems can provide a more
      comprehensive understanding of violence, establish patterns of under-reporting
      and better inform the development, implementation and evaluation of violence
      prevention initiatives. METHODS: Police violence with injury (VWI) crimed data
      and emergency department (ED) assault attendee data for South Wales were
      collected between 1 April 2014 and 31 March 2016 to examine the rates and
      patterns of VWI. Person identifiable data (PID) were cross-referenced to
      establish if certain victims or events were less likely to be reported to
      criminal justice services. RESULTS: A total of 18 316 police crimed VWI victims
      and 10 260 individual ED attendances with an assault-related injury were
      considered. The majority of ED assault attendances (59.0%) were unknown to
      police. The key demographic identified as under-reporting to police were young
      males aged 18-34 years, while a significant amount of non-reported assaults
      involved a stranger. The combined monthly age-standardised rates were
      recalculated and on average were 74.7 (95% CI 72.1 to 77.2) and 66.1 (95% CI 64.0
      to 68.2) per 100 000 population for males and females, respectively.
      Consideration of the additional ED cases resulted in a 35.3% and 18.1% increase
      on the original police totals for male and female VWI victims. CONCLUSIONS: This
      study identified that violence is currently undermeasured, demonstrated the
      importance of continued sharing of routinely collected ED data and highlighted
      the benefits of using PID from a number of services in a linked way to provide a
      more comprehensive picture of violence.

PMID- 29056593
TI  - Age-period-cohort analysis of trends in blood pressure and body mass index in
      children and adolescents in Hong Kong.
AB  - BACKGROUND: The declining or fluctuating trend in blood pressure (BP) despite the
      rising trend in body mass index (BMI) during childhood and adolescence is
      unexplained. We decomposed trends in BP and BMI to identify the relevance of
      early-life and contemporaneous factors. METHODS: We assessed the relative
      contribution of age, period and cohort to secular trends in BP in children and
      adolescents (9-18 years) from 1999 to 2014 and BMI (6-18 years) from 1996 to 2014
      in Hong Kong, China. RESULTS: After accounting for age, period effects
      contributed more than cohort effects to the overall fluctuating BP trend and the
      rising BMI trend observed in this Chinese population. For both sexes, BP fell
      from the start of period to a low point in 2003-2005 but then rose. BMI rose
      strongly across the period before levelling off in 2009-2010. Earlier cohorts
      (born in 1983-1984) had higher BP and BMI than later cohorts. CONCLUSION: With
      globalisation and associated lifestyle changes, successive generations of
      children and adolescents in a recently developed Chinese setting had lower BP and
      BMI, but this fall was offset until recently by population-wide increase in BMI.
      School-based health promotion efforts could have partly mitigated the population
      wide rise in child and adolescent BMI, while socioeconomic transition or other
      factors could be relevant to changes in BP between generations. Explaining these
      trends will help identify early-life factors that may contribute to a healthier
      start as well as contemporaneous factors that may protect against rising trends
      in adiposity.

PMID- 29056594
TI  - Primary schools and the amplification of social differences in child mental
      health: a population-based cohort study.
AB  - BACKGROUND: This paper examines socioeconomic inequalities in mental health at
      school entry and explores changes in these inequalities over the first 3 years of
      school. METHODS: The study utilises routinely collected mental health data from
      education records and demographic data at ages 4 and 7 years, along with
      administrative school-level data. The study was set in preschool establishments
      and schools in Glasgow City, Scotland. Data were available on 4011 children
      (59.4%)at age 4 years, and 3166 of these children were followed at age 7 years
      (46.9% of the population). The main outcome measure was the teacher-rated
      Goodman's Strengths and Difficulties Questionnaire (4-16 version) at age 7 years,
      which measures social, emotional and behavioural difficulties. RESULTS: Children
      living in the most deprived area had higher levels of mental health difficulties
      at age 4 years, compared with their most affluent counterparts (7.3%vs4.1% with
      abnormal range scores). There was a more than threefold widening of this
      disparity over time, so that by the age of 7 years, children from the most
      deprived area quintile had rates of difficulties 3.5 times higher than their more
      affluent peers. Children's demographic backgrounds strongly predicted their age 7
      scores, although schools appeared to make a significant contribution to mental
      health trajectories. CONCLUSIONS: Additional support to help children from
      disadvantaged backgrounds at preschool and in early primary school may help
      narrow inequalities. Children from disadvantaged backgrounds started school with
      a higher prevalence of mental health difficulties, compared with their more
      advantaged peers, and this disparity widened markedly over the first 3 years of
      school.

PMID- 29056595
TI  - Effectiveness of foot orthoses for the prevention of lower limb overuse injuries
      in naval recruits: a randomised controlled trial.
AB  - OBJECTIVES: To evaluate the effectiveness of prefabricated foot orthoses for the
      prevention of lower limb overuse injuries in naval recruits. METHODS: This study
      was a participant-blinded and assessor-blinded, parallel-group randomised
      controlled trial. Three-hundred and six participants aged 17-50 years who
      undertook 11 weeks of initial defence training at the Royal Australian Navy
      Recruit School (Cerberus, Australia) were randomised to a control group (flat
      insoles, n=153) or an intervention group (contoured, prefabricated foot orthoses,
      n=153). The combined incidence of medial tibial stress syndrome, patellofemoral
      pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain during the 11
      week training period were compared using incidence rate ratios (IRR). Data were
      analysed using the intention-to-treat principle. RESULTS: Sixty-seven injuries
      (21.9%) were recorded. The control and intervention group sustained 40 (26.1%)
      and 27 (17.6%) injuries, respectively (IRR 0.66, 95% CI 0.39 to 1.11, p=0.098).
      This corresponds to a 34% reduction in risk of developing medial tibial stress
      syndrome, patellofemoral pain, Achilles tendinopathy or plantar fasciitis/plantar
      heel for the intervention group compared with the control group. Participants in
      the prefabricated orthoses group were more likely to report at least one adverse
      event (20.3% vs 12.4%; relative risk (RR) 1.63, 95% CI 0.96 to 2.76; p=0.068;
      number needed to harm 13, 95% CI 6 to 253). The most common adverse events were
      foot blisters (n=20, 6.6%), arch pain (n=10, 3.3%) and shin pain (n=8, 2.6%).
      CONCLUSION: Prefabricated foot orthoses may be beneficial for reducing the
      incidence of lower limb injury in naval recruits undertaking defence training.
      TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry:
      ACTRN12615000024549.

PMID- 29056596
TI  - Is there a correlation between coaches' leadership styles and injuries in elite
      football teams? A study of 36 elite teams in 17 countries.
AB  - BACKGROUND: Do coaches' leadership styles affect injury rates and the
      availability of players in professional football? Certain types of leadership
      behaviour may cause stress and have a negative impact on players' health and well
      being. AIM: To investigate the transformational leadership styles of head coaches
      in elite men's football and to evaluate the correlation between leadership
      styles, injury rates and players' availability. METHODS: Medical staff from 36
      elite football clubs in 17 European countries produced 77 reports at four
      postseason meetings with a view to assessing their perception of the type of
      leadership exhibited by the head coaches of their respective teams using the
      Global Transformational Leadership scale. At the same time, they also recorded
      details of individual players' exposure to football and time-loss injuries.
      RESULTS: There was a negative correlation between the overall level of
      transformational leadership and the incidence of severe injuries (rho=-0.248;
      n=77; p=0.030); high levels of transformational leadership were associated with
      smaller numbers of severe injuries. Global Transformational Leadership only
      explained 6% of variation in the incidence of severe injuries (r2=0.062). The
      incidence of severe injuries was lower at clubs where coaches communicated a
      clear and positive vision, supported staff members and gave players encouragement
      and recognition. Players' attendance rates at training were higher in teams where
      coaches gave encouragement and recognition to staff members, encouraged
      innovative thinking, fostered trust and cooperation and acted as role models.
      CONCLUSIONS: There is an association between injury rates and players'
      availability and the leadership style of the head coach.

PMID- 29056597
TI  - Are athletes psychologically ready for sport following a concussion?

PMID- 29056598
TI  - Prevalence of illness, poor mental health and sleep quality and low energy
      availability prior to the 2016 Summer Olympic Games.
AB  - OBJECTIVE: Establish the prevalence of illness symptoms, poor sleep quality, poor
      mental health symptoms, low energy availability and stress-recovery state in an
      Olympic cohort late in the 3 months prior to the Summer Olympic Games. METHODS:
      Olympic athletes (n=317) from 11 sports were invited to complete questionnaires
      administered 3 months before the Rio 2016 Olympic Games. These questionnaires
      included the Depression, Anxiety and Stress Questionnaire, Perceived Stress
      Scale, Dispositional Resilience Scale, Recovery-Stress Questionnaire (REST-Q-52
      item), Low Energy Availability in Females Questionnaire (LEAF-Q), Epworth
      Sleepiness Scale, Pittsburgh Sleep Quality Index and custom-made questionnaires
      on probiotic usage and travel. Multiple illness (case) definitions were applied.
      ORs and attributable fractions in the population were used. Factor analyses were
      used to explore the relationships between variables. RESULTS: The response rate
      was of 42% (male, n=47, age 25.8+/-4.1 years; female, n=85, age 24.3+/-3.9
      years). Low energy availability was associated with sustaining an illness in the
      previous month (upper respiratory, OR=3.8, 95% CI 1.2 to 12). The main factor
      relating to illness pertained to a combination of anxiety and stress-recovery
      states (as measured by the REST-Q-52 item). All participants reported at least
      one episode of illness in the last month (100% prevalence). CONCLUSIONS: All
      participants reported at least one illness symptom in the previous month. Low
      energy availability was a leading variable associated with illness in Olympic
      class athletes. The estimates duration of symptoms ranged from 2 to 7 days.
      Factor analyses show the interdependence of various health domains and support
      multidisciplinary care.

PMID- 29056599
TI  - Early metastasis detected in patients with multifocal pulmonary ground-glass
      opacities (GGOs).

PMID- 29056601
TI  - Disagreement of diameter and volume measurements for pulmonary nodule size
      estimation in CT lung cancer screening.
AB  - : We studied 2240 indeterminate solid nodules (volume 50-500mm3) to determine the
      correlation of diameter and semi-automated volume measurements for pulmonary
      nodule size estimation. Intra-nodular diameter variation, defined as maximum
      minus minimum diameter through the nodule's center, varied by 2.8 mm (median,
      IQR:2.2-3.7 mm), so above the 1.5 mm cutoff for nodule growth used in Lung CT
      Screening Reporting and Data System (Lung-RADS). Using mean or maximum axial
      diameter to assess nodule volume led to a substantial mean overestimation of
      nodule volume of 47.2% and 85.1%, respectively, compared to semi-automated
      volume. Thus, size of indeterminate nodules is poorly represented by diameter.
      TRIAL REGISTRATION NUMBER: Pre-results, ISRCTN63545820.

PMID- 29056602
TI  - Protocolised early goal-directed therapy in patients with sepsis/septic shock
      does not result in improved survival compared with usual care with less invasive
      resuscitation strategies.

PMID- 29056603
TI  - Interpreting diagnostic tests with continuous results and no gold standard: a
      common scenario explained using the tuberculin skin test.
AB  - Practitioners of evidence-based medicine commonly encounter diagnostic tests with
      continuous results and no gold standard. In contrast, the traditional critical
      appraisal teachings assume a binary test (2*2 table) with a gold standard. In
      this guide, we use the example of the tuberculin skin test to illustrate a simple
      approach facilitated by using stratum-specific likelihood ratios and odds of
      developing future patient-important events. This approach can aid practitioners
      in the interpretation and application of diagnostic tests to patient care.

PMID- 29056600
TI  - International management platform for children's interstitial lung disease (chILD
      EU).
AB  - BACKGROUND: Children's interstitial lung diseases (chILD) cover many rare
      entities, frequently not diagnosed or studied in detail. There is a great need
      for specialised advice and for internationally agreed subclassification of
      entities collected in a register.Our objective was to implement an international
      management platform with independent multidisciplinary review of cases at
      presentation for long-term follow-up and to test if this would allow for more
      accurate diagnosis. Also, quality and reproducibility of a diagnostic
      subclassification system were assessed using a collection of 25 complex chILD
      cases. METHODS: A web-based chILD management platform with a registry and biobank
      was successfully designed and implemented. RESULTS: Over a 3-year period, 575
      patients were included for observation spanning a wide spectrum of chILD. In 346
      patients, multidisciplinary reviews were completed by teams at five international
      sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the
      diagnosis reached by the referring team was not confirmed by peer review. Among
      these, the diagnosis initially given was wrong (27%), imprecise (50%) or
      significant information was added (23%).The ability of nine expert clinicians to
      subcategorise the final diagnosis into the chILD-EU register classification had
      an overall exact inter-rater agreement of 59% on first assessment and after
      training, 64%. Only 10% of the 'wrong' answers resulted in allocation to an
      incorrect category. Subcategorisation proved useful but training is needed for
      optimal implementation. CONCLUSIONS: We have shown that chILD-EU has generated a
      platform to help the clinical assessment of chILD. TRIAL REGISTRATION NUMBER:
      Results, NCT02852928.

PMID- 29056604
TI  - Acupuncture is not as effective as infertility treatment in women with PCOS.

PMID- 29056605
TI  - Routine prophylaxis is not necessary to prevent renal scarring in children with
      urinary tract infection.

PMID- 29056606
TI  - Unblinded ASCOT study results do not rule out that muscle symptoms are an adverse
      effect of statins.

PMID- 29056607
TI  - Digital technology: coming of age?

PMID- 29056608
TI  - Acceptability of the Fitbit in behavioural activation therapy for depression: a
      qualitative study.
AB  - INTRODUCTION: Major depressive disorder is characterised by low mood and poor
      motivation. Literature suggests that increased physical activity has positive
      effects on alleviating depression. Fitness-tracking devices may complement
      behavioural activation (BA) therapy to improve physical activity and mental
      health in patients with depression. OBJECTIVES: To understand patients' perceived
      benefit from the Fitbit and explore themes associated with patient experiences.
      To compare perceived benefit, patient factors, Fitbit usage and Beck's Depression
      Inventory (BDI) scores. METHODS: Semistructured interviews were conducted with
      patients (n=36) who completed a 28-week BA group programme in a mood disorders
      outpatient clinic. All patients were asked to carry a Fitbit One device. We
      conducted thematic analyses on the interviews and exploratory quantitative
      analyses on patient characteristics, Fitbit usage, steps recorded, perceived
      benefit and BDI scores. FINDINGS: Twenty-three patients found the Fitbit helpful
      for their physical activity. Themes of positive experiences included self
      awareness, peer motivation and goal-setting opportunities. Negative themes
      included inconvenience, inaccuracies and disinterest. Age, baseline and change in
      BDI scores, prior physical activity goals and familiarity with technology were
      not associated with perceived benefit from the Fitbit or usage. Perceived benefit
      was significantly (p<0.01) associated with usage. CONCLUSIONS: Overall, the
      Fitbit is an acceptable tool to complement BA therapy for patients with
      depression. Many positive themes were concordant with current literature;
      however, patients also reported negative aspects that may affect use. CLINICAL
      IMPLICATIONS: Clinicians and researchers should consider both strengths and
      limitations of activity trackers when implementing them to motivate patients with
      depression. TRIAL REGISTRATION NUMBER: NCT02045771; Pre-results.

PMID- 29056609
TI  - Adjunctive avatar therapy for mentalization-based treatment of borderline
      personality disorder: a mixed-methods feasibility study.
AB  - BACKGROUND: Borderline personality disorder (BPD) is characterised by severe
      instability in emotions, identity, relationships and impulsive behaviour. One
      contributing factor to BPD is deficient mentalizing-our ability to understand the
      mental states of others and ourselves. Psychotherapies can be effective at
      reducing symptoms of BPD but effects are small. Innovative ways of enhancing
      existing therapies are therefore essential. OBJECTIVE: In a mixed-methods,
      feasibility and acceptability study, we adjuncted conventional mentalization
      based treatment (MBT) for BPD with avatar software (avatar-MBT). We wanted to
      test whether the enhanced visual narrative afforded by the software would
      facilitate therapy. METHODS: We used proprietary avatar software in four group
      MBT sessions. We collected data on uptake (n=15), dropout (n=4) and self-report
      measures (n=11) of mentalization and mood and conducted qualitative interviews to
      assess attitudes and beliefs (n=9). FINDINGS: Thematic analysis revealed five
      themes on the usefulness of avatar-MBT, including facilitating perspective
      taking, expression, emotional distancing, the big picture and group
      participation. The sixth theme suggested avatar-MBT is best placed within a group
      setting. There was no deterioration in symptoms as monitored by self-report
      measures. CONCLUSIONS: Qualitative data suggest that avatar-MBT is acceptable to
      patients with BPD who described it as enhancing conventional MBT and expressed a
      wish to continue using it. However, controlled trials are required to assess
      efficacy. CLINICAL IMPLICATIONS: Results suggest that avatar-MBT may be a viable
      option to enhance existing BPD treatment. Furthermore, we provide initial
      evidence that it is feasible to implement a digital adjunct within a group
      therapy setting.

PMID- 29056610
TI  - Problem-based, peer-to-peer global mental health e-learning between the UK and
      Somaliland: a pilot study.
AB  - BACKGROUND: WHO's mental health gap action programme intervention guide (mhGAP
      IG) is an evidence-based tool aimed at front-line health workers in low-income
      and middle-income countries (LMICs). Its potential to improve global mental
      health education, especially through digital technologies, has been little
      studied. Problem-based learning (PBL) is usually conducted face-to-face, but its
      remote application could facilitate cross-cultural education. OBJECTIVE: To
      evaluate PBL, applied to peer-to-peer global mental health e-learning (Aqoon),
      using mhGAP-IG. METHODS: Twelve pairs of UK and Somaliland medical students
      completed the full programme. Participants self-directedly met online, via the
      low-bandwidth Medicine Africa website, for PBL-style tutorials focused on modules
      of the mhGAP-IG, V.2.0. Preparticipation and postparticipation surveys used mixed
      methods to evaluate Aqoon, including the Attitudes Toward Psychiatry (ATP-30)
      instrument. FINDINGS: Median ATP-30 scores for Somaliland (82.0 vs 95.0, p=0.003)
      and UK students (82.0 vs 95.0, p=0.011) improved significantly following Aqoon.
      Qualitative feedback showed that participants valued peer connectivity and
      learning about cultural and psychosocial differences in their partner's country.
      Somaliland students were motivated by clinical learning and UK students by global
      health education. Feedback on the PBL structure was positive. CONCLUSIONS:
      Digital PBL represents an innovative method to extend the benefits of mhGAP-IG
      beyond front-line clinical staff, to healthcare students in LMICs. CLINICAL
      IMPLICATIONS: Educational resource limitations in LMICs may be overcome using
      digital platforms and PBL. Replication with non-medical healthcare students is
      the next step for this model to explore Aqoon's relevance to pressing global
      mental health workforce challenges.

PMID- 29056612
TI  - Controllable release of interleukin-4 in double-layer sol-gel coatings on TiO2
      nanotubes for modulating macrophage polarization.
AB  - Classically activated M1 macrophages and alternatively activated M2 macrophages
      play key roles in regulating immune responses. M1 macrophages initiate
      angiogenesis in the early stages of wound healing or after implantation. However,
      their prolonged activation can lead to chronic inflammation. We speculated that
      biomedical implants with specific properties can induce a shift from M1 to M2
      macrophages at a specific time point to promote tissue repair and wound healing.
      To investigate this possibility, drug-loaded double-layer sol-gel coatings were
      fabricated on TiO2 nanotubes (TNTs), which were used to modulate the switch from
      the M1 to the M2 phenotype by controlled release of interleukin (IL)-4. The lower
      sol-gel layer with IL-4 consisted of a carboxymethyl chitosan (CMCS) hydrogel, 1
      ethyl-3-(3-dimethylaminopropyl) carbodiimide, and N-hydroxysuccinimide as a
      crosslinker (IL4/TNT). The upper layer fabricated on the IL4/TNT sample was
      another type of CMCS hydrogel that used genipin (GP) as a crosslinker
      (GP/IL4/TNT). We found that IL-4 was released from GP/IL4/TNTs in a controlled
      manner, with the greatest release occurring after 72 h. GP/IL4/TNT stimulated the
      polarization of macrophages from the M1 to M2 phenotype after the macrophage
      polarization from the M0 to M1 phenotype. This provides a template for the
      fabrication of biomaterials that can direct macrophage polarization and stimulate
      tissue regeneration following the initial inflammatory response to implants.

PMID- 29056611
TI  - Medical students' perceptions of their learning environment during a mandatory
      research project.
AB  - Objectives: To explore medical students' perceptions of their learning
      environment during a mandatory 20-week scientific research project. Methods: This
      cross-sectional study was conducted between 2011 and 2013. A total of 651 medical
      students were asked to fill in the Clinical Learning Environment, Supervision,
      and Nurse Teacher (CLES+T) questionnaire, and 439 (mean age 26 years, range 21
      40, 60% females) returned the questionnaire, which corresponds to a response rate
      of 67%. The Mann-Whitney U test or the Kruskal-Wallis test were used to compare
      the research environments. Results: The item My workplace can be regarded as a
      good learning environment correlated strongly with the item There were sufficient
      meaningful learning situations (r= 0.71, p<0.001). Overall satisfaction with
      supervision correlated strongly with the items interaction (r=0.78, p < 0.001),
      feedback (r=0.76, p<0.001), and a sense of trust (r=0.71, p < 0.001). 
      Supervisors' failures to bridge the gap between theory and practice or to explain
      intended learning outcomes were important negative factors.  Students with basic
      science or epidemiological projects rated their learning environments higher than
      did students with clinical projects (chi2(3, N=437)=20.29, p<0.001). Conclusions:
      A good research environment for medical students comprises multiple meaningful
      learning activities, individual supervision with continuous feedback, and a
      trustful atmosphere including interactions with the whole staff.  Students should
      be advised that clinical projects might require a higher degree of student
      independence than basic science projects, which are usually performed in research
      groups where members work in close collaboration.

PMID- 29056613
TI  - Evaluating the Sustainability of School-Based Health Centers.

PMID- 29056614
TI  - Evaluating the Sustainability of School-Based Health Centers.
AB  - BACKGROUND: The United States is facing a surge in the number of school-based
      health centers (SBHCs) owing to their success in delivering positive health
      outcomes and increasing access to care. To preserve this success, experts have
      developed frameworks for creating sustainable SBHCs; however, little research has
      affirmed or added to these models. OBJECTIVES: This research seeks to analyze
      elements of sustainability in a case study of three SBHCs in San Diego,
      California, with the purpose of creating a research-based framework of SBHC
      sustainability to supplement expertly derived models. METHODS: Using a mixed
      methods study design, data were collected from interviews with SBHC stakeholders,
      observations in SBHCs, and SBHC budgets. A grounded theory qualitative analysis
      and a quantitative budget analysis were completed to develop a theoretical
      framework for the sustainability of SBHCs. RESULTS: Forty-one interviews were
      conducted, 6 hours of observations were completed, and 3 years of SBHC budgets
      were analyzed to identify care coordination, community buy-in, community
      awareness, and SBHC partner cooperation as key themes of sustainability promoting
      patient retention for sustainable billing and reimbursement levels. CONCLUSIONS:
      These findings highlight the unique ways in which SBHCs gain community buy-in and
      awareness by becoming trusted sources of comprehensive and coordinated care
      within communities and among vulnerable populations. Findings also support ideas
      from expert models of SBHC sustainability calling for well-defined and executed
      community partnerships and quality coordinated care in the procurement of
      sustainable SBHC funding.

PMID- 29056615
TI  - Enrolling Family Participants in a Statewide Implementation Trial of an Evidence
      Based Treatment.
AB  - BACKGROUND: Community-based research with families is subject to unique
      challenges in recruiting and enrolling participants, particularly when
      researchers do not have face-to-face contact with participants. OBJECTIVES: To
      identify strategies that overcome challenges associated with the recruitment and
      enrollment of family participants from community behavioral health settings into
      a research study. METHODS: We used a case study design to describe lessons
      learned during the recruitment and enrollment phases of a large-scale study of
      the implementation of an evidence-based treatment (EBT) across the Commonwealth
      of Pennsylvania. LESSONS LEARNED: Key lessons identified include the early
      involvement of stakeholders, engaging clinicians in the research process,
      establishing a research-community relationship, and using a flexible, ongoing
      recruitment approach. CONCLUSIONS: In large-scale community-based research,
      engagement, recruitment, and enrollment strategies are particularly crucial. The
      strategies included in this paper are relevant to multiple disciplines involving
      community-based research.

PMID- 29056616
TI  - Facilitating Meaningful Engagement on Community Advisory Committees in Patient
      Centered Outcome Research.
AB  - BACKGROUND: Reflecting on the processes and practices used to engage community
      stakeholders in patient-centered outcome research strengthens participation at
      the project level and contributes more broadly to developing knowledge about
      effective participatory processes and methods. OBJECTIVES: We conducted a process
      evaluation of ongoing activities of a Patient Advisory Committee (PAC) formed
      around the development of an individualized decision aid for older women with
      early stage breast cancer. METHODS: In-depth qualitative interviews were
      conducted with PAC members to obtain their input on the effectiveness of the
      project's participatory approach and identify barriers to participation. Results
      and Lessons Learned: Although there was general support for the aims of the
      study, patient knowledge gaps and meeting facilitation style limited
      participation. Members made suggestions on improving collaboration within the
      group that, when implemented, resulted in increased participation and revitalized
      interest in the project. CONCLUSIONS: Results suggest that engaging committee
      members in a process of evaluation and collective reflection during a research
      collaboration can break down barriers to collaboration, build relationships,
      create opportunities for co-learning and strengthen researchers' capacity to
      engage meaningfully with stakeholders.

PMID- 29056619
TI  - Increasing Empathy and Conflict Resolution Skills through Nonviolent
      Communication (NVC) Training in Latino Adults and Youth.
AB  - BACKGROUND: Children of Latino immigrants often are torn between their native
      homes and new communities. Having supportive interpersonal relationships
      increases resilience to delinquent and violent behaviors stemming from
      immigration challenges. Communication fostering empathy may improve conflict
      resolution and supportive relationships. OBJECTIVES: Community-based
      participatory research (CBPR) was conducted to evaluate the impact of nonviolent
      communication (NVC) trainings in Latino adults and youth. METHODS: Four sessions
      in NVC were provided by bilingual Latino trainers for Latino adults and youth.
      Pre- and post-training focus groups evaluated effectiveness of training. RESULTS:
      Three themes emerged from adult post training focus groups-enter the others'
      shoes, making a change, and learning in community. The youth reflected on new
      ways to manage conflict and understand emotions. LESSONS LEARNED: Research team
      embedded in community increased success. However, inconsistent participant
      attendance precluded quantitative analyses. CONCLUSION: Seeds were planted in
      this Latino community for future potential projects.

PMID- 29056618
TI  - Development of an Online Smoking Cessation Curriculum for Pacific Islanders: A
      Community-Based Participatory Research Approach.
AB  - BACKGROUND: Pacific Islanders (PIs) have one of the highest rates of cigarette
      use, but evidence-based smoking cessation programs designed specifically for PIs
      are practically nonexistent. OBJECTIVES: This paper reports on the development of
      a culturally tailored smoking cessation curriculum designed specifically for
      young adult PIs using a community-based participatory research (CBPR) approach.
      This paper demonstrates the shared leadership and equal contribution of community
      and academic partnerships. METHODS: Together community and academic partners
      conceptualized and developed a smoking cessation curriculum. Data from formative
      studies shaped the various components of the educational modules. RESULTS: Eight
      educational modules were developed through CBPR. Information on the dangers of
      cigarettes, benefits to cessation, and ways to cope with cravings and stress
      through cognitive behavioral therapy were offered in both narrative and non
      narrative formats. CONCLUSIONS: Use of CBPR is critical in the development of the
      curriculum because it allowed for the sharing of ideas and knowledge between
      academics and community members.

PMID- 29056617
TI  - Cultural Adaptation of Diabetes Self-Management Education for Marshallese
      Residing in the United States: Lessons Learned in Curriculum Development.
AB  - BACKGROUND: Type 2 diabetes is a significant public health problem, with U.S.
      Pacific Islander communities bearing a disproportionate burden. The Marshallese
      are a Pacific Islander community that has significant inequities in diabetes, yet
      few evidence-based diabetes interventions have been developed to address this
      inequity. OBJECTIVES: We used a community-based participatory research (CBPR)
      approach to adapt an evidence-based diabetes self-management education (DSME)
      intervention for the Marshallese. METHODS: Our team used the Cultural Adaptation
      Process Model, in addition to an iterative process consisting of formative data
      and previous literature review, and engagement with community and academic
      experts. LESSONS LEARNED: Specific cultural considerations were identified in
      adapting DSME components, including the dichotomous versus gradient
      conceptualization of ideas, the importance of engaging the entire family, the use
      of nature analogies, and the role of spirituality. CONCLUSIONS: We identified key
      cultural considerations to incorporate into a diabetes self-management program
      for the Marshallese. The insights gained can inform others' work with Pacific
      Islanders.

PMID- 29056620
TI  - Promoting Resilience by Improving Children's Sleep: Feasibility Among Families
      Living in Supportive Housing.
AB  - BACKGROUND: Poverty has been linked to sleep disruption, which is in turn
      associated with health and behavior problems. Sleep disturbance may be a key
      mechanism by which poverty affects child development. OBJECTIVE: To evaluate the
      feasibility, appeal, and promise of a brief sleep-promoting intervention for low
      income families with 4- to 8-year-old children in site-based supportive housing.
      METHODS: University researchers and community partners developed a sleep
      promoting intervention (family workshop and bedtime relaxation routine) that was
      implemented at one supportive housing site. Multiple methods were used to assess
      feasibility and preliminary effectiveness in 11 participating families. RESULTS:
      Intervention and research activities were acceptable to families, but adherence
      to daily sleep measures was low. Most parents reported high satisfaction, and
      data showed trends of improvement in children's sleep, behavior, and executive
      function (EF). CONCLUSIONS: A brief sleep-promoting intervention for children in
      disadvantaged families showed feasibility and promise. Future studies are needed
      to test the efficacy of a refined version of this sleep intervention with
      families in similar situations, focusing on decreasing burden, tailoring
      interventions, and sustaining change.

PMID- 29056622
TI  - Essentials of Research Engagement With Native American Tribes: Data Collection
      Reflections of a Tribal Research Team.
AB  - BACKGROUND: A community-based participatory research (CBPR) approach,
      particularly relevant when collecting data on sensitive topics, was employed to
      partner with reservation tribes to assess suicide risk among Native American (NA)
      youth. OBJECTIVES: To share relationship-building strategies used by an NA
      research team to build a partnership for collecting data. METHODS: Our collective
      knowledge was used to cultivate a deeper understanding of the community, build
      trust, and partner to engage in a respectful tribally appropriate research
      process. This approach provided a solid foundation for our inquiry on risk and
      protective factors for youth suicide. LESSONS LEARNED: A culturally grounded
      approach recognizes the importance of (1) ethnic concordance, (2) cultural
      acceptance, (3) taking time to build trust, and (4) using CBPR principles.
      CONCLUSIONS: Significant participation of Native researchers in sensitive topics
      research with tribal communities is a promising strategy for trust building and
      partnership development. Understanding tribal context is imperative.

PMID- 29056623
TI  - The RAISE Coalition: Lessons Learned From a Multisector Coalition Used to
      Implement High-impact Population-Wide Strategies in Cleveland, Ohio.
AB  - BACKGROUND: Recent public health initiatives include policy, systems, and
      environmental (PSE) strategies with the aim of improving community health. These
      high-impact, population-wide strategies provide opportunities for multisector
      coalitions to engage and inform the implementation process to ultimately reach
      underrepresented communities, like Asian Americans and Pacific Islanders (AAPIs).
      OBJECTIVES: The purpose of this article is to discuss (1) the objectives of
      "Reaching Asian Americans through Innovative and Supportive Engagement," (RAISE)
      a multisector coalition (2) describe the process in which the coalition was
      engaged in, and (3) share lessons learned that can inform future partnerships
      with various sectors that reach AAPI communities that are highly diverse and in
      geographically dispersed areas. METHODS: Asian Services In Action, a community
      based organization in Cleveland, Ohio recruited 10 member organizations to
      participate in a multisector coalition to identify, plan and implement a PSE
      strategy reaching AAPIs. LESSONS LEARNED: Key lessons learned include: the need
      to navigate competing priorities for member organizations; the value in creating
      a space where racial/ethnic diversity and cultural adaption are discussed; and
      the importance of creating a shared learning community for coalition members.
      CONCLUSIONS: As the public health landscape shifts toward effectively improving
      community health through PSE strategies, it is vital that multisector coalitions
      are included to potentially have the greatest impact in health overall and to
      increase community engagement and buy-in.

PMID- 29056624
TI  - Community Health Warriors: Marshallese Community Health Workers' Perceptions and
      Experiences with CBPR and Community Engagement.
AB  - Our manuscript highlights the viewpoints and reflections of the native
      Marshallese community health workers (CHWs) engaged in research with the local
      Marshallese community in Northwest Arkansas. In particular, this paper documents
      the vital role Marshallese CHWs play in the success of programs and research
      efforts. The negative health effects of nuclear testing in the Marshall Islands
      has been passed down through many generations, along with unfavorable attitudes
      toward the U.S. government and researchers. However, the community-based
      participatory research (CBPR) approach used by the University of Arkansas for
      Medical Sciences (UAMS) has allowed the native Marshallese CHWs to become
      advocates for the Marshallese community. The use of native CHWs has also leveled
      the power dynamics that can be a barrier to community-based research, and has
      strengthened trust with community stakeholders. Our paper shows how using
      Marshallese CHWs can produce positive health outcomes for the Marshallese
      community.

PMID- 29056625
TI  - The Development of a Community Engagement Workshop: A Community-Led Approach for
      Building Researcher Capacity.
AB  - BACKGROUND: Although community-engaged research (CEnR) is increasingly promoted
      in the literature, academic programs often fail to prepare researchers for the
      critical, ethical, and power issues involved in CEnR. This article documents a
      community-created and led workshop for CEnR researchers. OBJECTIVES: The
      workshop's main objective is to increase researchers' knowledge and felt
      experience of the "dos and don'ts" of CEnR in three research domains: entering
      the community, accommodating the realities and constraints of community-based
      organizations, and dissemination. METHODS: The Dos and Don'ts of Community
      Engagement workshop was developed and implemented by the Arkansas Prevention
      Research Center's (PRC) Community Advisory Board (CAB) in partnership with
      faculty and staff from the Fay W. Boozman College of Public Health (COPH) at the
      University of Arkansas for Medical Sciences (UAMS). The CAB developed the
      workshop using a collaborative, iterative process grounded in popular education.
      Teaching approaches include video testimonials, reverse role-play scenarios, and
      group reflections and debriefings. Implementation included dry runs with CAB
      members, a pilot, and five workshops with UAMS faculty, dissemination to an out
      of-state university, and post-assessment surveys of participants. CONCLUSIONS:
      Participants' written evaluations suggest the workshop was engaging and
      successfully motivated researchers to adopt new perspectives, acknowledge power
      imbalances across the domains, self-reflect about their role as researchers, and
      consider solutions to these problems. Other reported outcomes included the
      development of relationships leading to new CEnR projects, unanticipated learning
      experienced by community member participants, requests for additional workshops
      through UAMS' Translational Research Institute, and development of a train-the
      trainer manual and accompanying video guide.

PMID- 29056626
TI  - I Always Wanted to be a Father.

PMID- 29056627
TI  - Editors' Note.

PMID- 29056628
TI  - Focusing on the Present: Cancer, Pregnancy and the Fertility Conversation.

PMID- 29056629
TI  - The Death of Biological Motherhood.

PMID- 29056630
TI  - Cancer and Fertility.
AB  - This symposium includes 12 personal narratives from individuals who have faced a
      cancer diagnosis-either their own or their child's-where the disease itself, or
      their treatment, threatened future fertility. Three additional stories are
      available in the online supplement. Three commentaries on these narratives are
      written by an expert in oncofertility, a healthcare ethicist, and a pediatrician
      completing a fellowship in hematology/oncology. The observations and insights
      these authors share underscore the importance of addressing fertility loss and
      preservation early in the cancer journey. These contributions will help
      clinicians better understand the significance of fertility issues for children
      and younger adults diagnosed with cancer. They also can contribute to policy
      discussions about the role of health insurance in meeting the needs of cancer
      patients. Patients and families reading these stories and commentaries will
      appreciate learning from the experiences of others.

PMID- 29056631
TI  - Narrative Symposium: Cancer and Fertility.

PMID- 29056632
TI  - Single Base Life.

PMID- 29056634
TI  - The Fire Cancer.

PMID- 29056633
TI  - A Biological Child Does Not Repair the Injustice of Breast Cancer at a Young Age.

PMID- 29056636
TI  - My Story of Cancer Infertility.

PMID- 29056635
TI  - Don't Focus on Statistics.

PMID- 29056637
TI  - My 18 Little Miracles.

PMID- 29056638
TI  - Cancer Isn't Fair.

PMID- 29056639
TI  - Tragedy and Triumph: Overcoming Cancer and Infertility.

PMID- 29056640
TI  - Words We Never Knew.

PMID- 29056641
TI  - What We Didn't Know.

PMID- 29056642
TI  - Mitigating Surprises: How Conversations with Caregivers Could Empower Young
      Cancer Patients to Determine their own Fertile Futures.

PMID- 29056643
TI  - I Saw it Coming: My Testicular Cancer Infertility Story.

PMID- 29056644
TI  - Devastation and Hope-Stories of Fertility in Oncology.
AB  - Having children is a deeply held desire for many people. After a cancer
      diagnosis, fertility is often threatened by cancer treatments. The choice to
      pursue fertility preservation often necessitates a delay in starting cancer
      treatment which may negatively impact the patient. Fertility decisions are laden
      with heavy emotional burden and multiple ethical challenges. The narratives in
      this symposium provide rich emotional context, including allusions to failure,
      loss, guilt, fear, anger, hope, and acceptance. Given the important role of
      emotion in moral reasoning, exploration of these emotions supports further
      discussion of ethical challenges. Subsequent ethical themes include cost and
      unequal access, poor communication, and differing priorities between healthcare
      providers and patients. These stories draw us into the fearful intersection of
      cancer and infertility, yet they leave us with hope that many current challenges
      can be improved with open discussion and sensitivity to the needs of others.

PMID- 29056645
TI  - Fertility Lost-Fertility Found: Narratives from the Leading Edge of
      Oncofertility.
AB  - A cancer diagnosis at a young age creates one of the most existential crises one
      can imagine. The good news is that for many of these young patients, they will
      survive their diagnosis. They will be told of the side effects of treatment
      including loss of hair but will not be told of the other losses associated with
      their reproductive function-loss of menstrual cycles, early menopause and the
      potential for pregnancy for women, loss of viable sperm for men, and loss of
      sexual libido in both cases. Not all cancer treatments result in the same series
      of fertility effects so one of the issues that physicians face is determining
      what the best course of fertility sparing options should be. That dilemma is in
      the best cases-in many more cases the patients are not told about the potential
      loss of fertility and are left with a myriad of financial and psychological
      decisions and costs that they navigate on their own. The stories in this
      symposium capture this unfolding series of events. Some cases result in good
      prognosis and fertility options that are appropriate and the patients are happy
      with the outcome. Others express regret and loss of potential now beyond their
      reach. As a practitioner in the field I find these narratives reinforce how
      important the broad research field of oncofertility is. These patients are at the
      forefront of emerging technologies and emerging medical interactions between
      disciplines that were miles away from each other. The stories illuminate the
      individual and the universal and are critical to the overall context of this
      field.

PMID- 29056646
TI  - NIB Commentary on Oncofertility Stories.
AB  - The authors of these stories describe tales of struggle with cancer and secondary
      infertility. Yet, they each have a different response to similar circumstances.
      Their stories touch on a lack of informed consent regarding infertility,
      spiritual discussions of the problem of evil, the need for improved collaboration
      among physicians to further care of the whole person, societal norms regarding
      reproduction and gender roles, the injustice of cancer in young people, and other
      topics. Of note, no stories mention prominent ethical concerns of in-vitro
      fertilization like how couples should deal with "extra" frozen embryos or
      concerns about the potential for commodification of children. This shows a
      disconnect between the concerns of bioethicists and the concerns of real patients
      facing actual problems. Both cancer patients and providers can learn something
      from these stories that directly apply to their lives.

PMID- 29056647
TI  - Ethical Challenges for Patient Access to Physical Therapy: Views of Staff Members
      from Three Publicly-Funded Outpatient Physical Therapy Departments.
AB  - Demographic change and changing population needs are important drivers of
      increased demand for rehabilitation. These developments place significant stress
      on access to physical therapy services, as current resources are insufficient to
      meet the growing demand. This situation presents ethical challenges for physical
      therapists and others involved in managing wait lists and prioritizing access to
      services. The purpose of this study is to explore how outpatient physical therapy
      department (OPD) staff experience ethical issues relating to access to physical
      therapy services. We conducted semi-structured interviews with 13 participants
      who were staff at three publicly-funded OPDs in Montreal, Quebec, Canada. Using
      interpretive description methodology, we developed four themes related to access
      to physical therapy services: 1) negotiating access to physical therapy services;
      2) navigating a complex system with outside influences and constraints, such as
      professional regulation and third-party payers; 3) managing wait lists
      responsibly; and 4) striving to be a good professional in a non-ideal world.
      Across the four themes, two main sources of tension that influence the staff were
      identified in relation to the experience of wait list management: responsibility
      and power. This study highlights how difficult it is for OPD staff to balance
      competing interests and values, and to respond to outside influences, when making
      resource allocation decisions. Until resource limitations are addressed, wait
      lists may be an unavoidable feature of many OPDs in the Canadian public health
      care system. Improving fairness in the access to and distribution of services is
      thus important in ensuring that professionals are able to treat patients based on
      their clinical needs, and in a timely fashion.

PMID- 29056648
TI  - "We Didn't Consent to This".
AB  - Patients and their families have identified the need for ongoing and effective
      communication as one of the important aspects of medical care, especially when
      the cessation of disease-modifying therapies is being considered at the end-of
      life (EOL). Despite recognizing that this communication is extremely important,
      clinicians are uneasy and find themselves inadequately trained to "break bad
      news" and manage emotional responses from the patient/family. The inherent
      difficulties in accurately predicting prognosis and discussing potential
      complications make these conversations even more challenging. In most
      circumstances, patients and their families want to know the truth about their
      disease and what will be done to make them feel better, and to receive enough
      information to help them choose a course of action. For many terminally ill
      patients and their families who have elected to transfer to the palliative care
      unit (PCU) for EOL care, the assumption is that most of these conversations have
      already been held, and the ongoing focus becomes managing these patients'
      physical and psychological sources of distress, validating their and their
      families' emotional responses and preparing them for what is to come. This case
      report illustrates the need for cultural understanding and clear communication
      among physicians, members of the clinical team, and patients and their family
      members.

PMID- 29056651
TI  - Mercury, Lead, Cadmium, Arsenic, Chromium and Selenium in Feathers of Shorebirds
      during Migrating through Delaware Bay, New Jersey: Comparing the 1990s and
      2011/2012.
AB  - Understanding temporal changes in contaminant levels in coastal environments
      requires comparing levels of contaminants from the same species from different
      time periods, particularly if species are declining. Several species of
      shorebirds migrating through Delaware Bay have declined from the 1980s to the
      present. To evaluate some contaminants as cause for the declines, we examine
      levels of mercury, lead, cadmium, arsenic, chromium and selenium in feathers of
      red knot (Calidris canutus, N = 46 individuals), semipalmated sandpiper (Calidris
      pusilla, N = 70) and sanderling (Calidris alba, N = 32) migrating through
      Delaware Bay, New Jersey, USA, from 1991 to 1992 (N = 40), 1995 (N = 28), and
      2011-2012 (N = 80) to determine if levels have changed. We found: (1) arsenic,
      chromium, and lead increased in red knot and decreased in semipalmated sandpiper;
      (2) cadmium decreased in semipalmated sandpipers; (3) mercury decreased in red
      knot and sanderlings; (4) selenium decreased in red knot and increased in
      semipalmated sandpipers. In 2011/2012 there were significant interspecific
      differences for arsenic, mercury and selenium. Except for selenium, the element
      levels were well below levels reported for feathers of other species. The levels
      in feathers in red knots, sanderling, and semipalmated sandpipers from Delaware
      Bay in 2011/2012 were well below levels in feathers that are associated with
      effect levels, except for selenium. Selenium levels ranged from 3.0 ug.g-1 dry
      weight to 5.8 ug.g-1 (semipalmated sandpiper), within the range known to cause
      adverse effects, suggesting the need for further examination of selenium levels
      in birds. The levels of all elements were well below those reported for other
      marine species, except for selenium, which was near levels suggesting possible
      toxic effects.

PMID- 29056650
TI  - Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms.
AB  - Mercury, cadmium, arsenic and lead are among priority metals for toxicological
      studies due to the frequent human exposure and to the significant burden of
      disease following acute and chronic intoxication. Among their common
      characteristics is chemical affinity to proteins and non-protein thiols and their
      ability to generate cellular oxidative stress by the best-known Fenton mechanism.
      Their health effects are however diverse: kidney and liver damage, cancer at
      specific sites, irreversible neurological damages with metal-specific features.
      Mechanisms for the induction of oxidative stress by interaction with the cell
      thiolome will be presented, based on literature evidence and of experimental
      findings.

PMID- 29056652
TI  - L-Dopa and Brain Serotonin System Dysfunction.
AB  - L-dopa is used to treat the motor symptoms associated with Parkinson's disease, a
      neurodegenerative movement disorder characterized by a loss of dopamine neurons.
      L-dopa is the precursor to dopamine and crosses the blood-brain barrier to
      increase dopamine neurotransmission. This review will focus on the findings that
      dopamine produced from L-dopa is mediated in part by serotonin neurons. Direct
      evidence will be provided that increases in dopamine cause oxidative stress and
      damage serotonin neurons. Similarly, chronic L-dopa produces deficits in
      serotonin neurotransmission, including decreases in both serotonin cell bodies
      within the dorsal raphe and serotonin neurotransmitter concentrations in several
      forebrain regions. Since serotonin is involved in many important physiological
      processes including mood and cognition, L-dopa induced serotonin deficits may
      play a role in the side-effect symptoms observed in Parkinson's disease patients
      treated with L-dopa.

PMID- 29056654
TI  - Live and Let Die: Roles of Autophagy in Cadmium Nephrotoxicity.
AB  - The transition metal ion cadmium (Cd2+) is a significant environmental
      contaminant. With a biological half-life of ~20 years, Cd2+ accumulates in the
      kidney cortex, where it particularly damages proximal tubule (PT) cells and can
      result in renal fibrosis, failure, or cancer. Because death represents a powerful
      means by which cells avoid malignant transformation, it is crucial to clearly
      identify and understand the pathways that determine cell fate in chronic Cd2+
      nephrotoxicity. When cells are subjected to stress, they make a decision to adapt
      and survive, or-depending on the magnitude and duration of stress-to die by
      several modes of death (programmed cell death), including autophagic cell death
      (ACD). Autophagy is part of a larger system of intracellular protein degradation
      and represents the channel by which organelles and long-lived proteins are
      delivered to the lysosome for degradation. Basal autophagy levels in all
      eukaryotic cells serve as a dynamic physiological recycling system, but they can
      also be induced by intra- or extracellular stress and pathological processes,
      such as endoplasmic reticulum (ER) stress. In a context-dependent manner,
      autophagy can either be protective and hence contribute to survival, or promote
      death by non-apoptotic or apoptotic pathways. So far, the role of autophagy in
      Cd2+-induced nephrotoxicity has remained unsettled due to contradictory results.
      In this review, we critically survey the current literature on autophagy in Cd2+
      induced nephrotoxicity in light of our own ongoing studies. Data obtained in
      kidney cells illustrate a dual and complex function of autophagy in a stimulus-
      and time-dependent manner that possibly reflects distinct outcomes in vitro and
      in vivo. A better understanding of the context-specific regulation of cell fate
      by autophagy may ultimately contribute to the development of preventive and novel
      therapeutic strategies for acute and chronic Cd2+ nephrotoxicity.

PMID- 29056655
TI  - Taxane-Induced Peripheral Neurotoxicity.
AB  - Taxane-derived agents are chemotherapy drugs widely employed in cancer treatment.
      Among them, paclitaxel and docetaxel are most commonly administered, but newer
      formulations are being investigated. Taxane antineoplastic activity is mainly
      based on the ability of the drugs to promote microtubule assembly, leading to
      mitotic arrest and apoptosis in cancer cells. Peripheral neurotoxicity is the
      major non-hematological adverse effect of taxane, often manifested as painful
      neuropathy experienced during treatment, and it is sometimes irreversible.
      Unfortunately, taxane-induced neurotoxicity is an uncertainty prior to the
      initiation of treatment. The present review aims to dissect current knowledge on
      real incidence, underlying pathophysiology, clinical features and predisposing
      factors related with the development of taxane-induced neuropathy.

PMID- 29056656
TI  - Speciation in Metal Toxicity and Metal-Based Therapeutics.
AB  - Metallic elements, ions and compounds produce varying degrees of toxicity in
      organisms with which they come into contact. Metal speciation is critical to
      understanding these adverse effects; the adjectives "heavy" and "toxic" are not
      helpful in describing the biological properties of individual elements, but
      detailed chemical structures are. As a broad generalization, the metallic form of
      an element is inert, and the ionic salts are the species that show more
      significant bioavailability. Yet the salts and other chelates of a metal ion can
      give rise to quite different toxicities, as exemplified by a range of
      carcinogenic potential for various nickel species. Another important distinction
      comes when a metallic element is organified, increasing its lipophilicity and
      hence its ability to penetrate the blood brain barrier, as is seen, for example,
      with organic mercury and tin species. Some metallic elements, such as gold and
      platinum, are themselves useful therapeutic agents in some forms, while other
      species of the same element can be toxic, thus focusing attention on species
      interconversions in evaluating metal-based drugs. The therapeutic use of metal
      chelating agents introduces new species of the target metal in vivo, and this can
      affect not only its desired detoxification, but also introduce a potential for
      further mechanisms of toxicity. Examples of therapeutic iron chelator species are
      discussed in this context, as well as the more recent aspects of development of
      chelation therapy for uranium exposure.

PMID- 29056653
TI  - Multifactorial Origin of Neurodevelopmental Disorders: Approaches to
      Understanding Complex Etiologies.
AB  - A significant body of evidence supports the multifactorial etiology of
      neurodevelopmental disorders (NDDs) affecting children. The present review
      focuses on early exposure to environmental chemicals as a risk factor for
      neurodevelopment, and presents the major lines of evidence derived from
      epidemiological studies, underlying key uncertainties and research needs in this
      field. We introduce the exposome concept that, encompassing the totality of human
      environmental exposures to multiple risk factors, aims at explaining individual
      vulnerability and resilience to early chemical exposure. In this framework, we
      synthetically review the role of variable gene backgrounds, the involvement of
      epigenetic mechanisms as well as the function played by potential effect
      modifiers such as socioeconomic status. We describe laboratory rodent studies
      where the neurodevelopmental effects of environmental chemicals are assessed in
      the presence of either a "vulnerable" gene background or adverse pregnancy
      conditions (i.e., maternal stress). Finally, we discuss the need for more
      descriptive and "lifelike" experimental models of NDDs, to identify candidate
      biomarkers and pinpoint susceptible groups or life stages to be translated to
      large prospective studies within the exposome framework.

PMID- 29056657
TI  - Updates on Oxaliplatin-Induced Peripheral Neurotoxicity (OXAIPN).
AB  - Oxaliplatin-induced peripheral neuropathy (OXAIPN) is of great clinical interest
      as it ranks among the most common dose limiting toxicities of oxaliplatin (OXA)
      administration with an obvious impact on the outcome of cancer patients. In
      addition, OXAIPN has a detrimental effect on the quality of life of cancer
      patients because it can be long lasting or even permanent. It has a unique
      spectrum of clinical presentation, being manifested with two distinct syndromes:
      the acute neurotoxicity that appears soon after OXA administration and is usually
      transient, and the chronic cumulative syndrome that resembles the characteristics
      of all platinum compounds. Despite advances in research in relation to the
      elucidation of the true OXAIPN pathogenesis, characteristics and management,
      there are still several open issues to be addressed. One of the most important
      open issues is to determine reliable biomarkers to allow prompt identification of
      patients at high risk to develop OXAIPN and towards this view well designed
      genome wide analyses are warranted to adequately address this gap in knowledge.
      Recent updates are provided in this article in relation to the pathogenesis,
      clinical characteristics, pharmacogenetics and management of OXAIPN.

PMID- 29056658
TI  - Mitochondrial Dysfunction in Chemotherapy-Induced Peripheral Neuropathy (CIPN).
AB  - The mitochondrial dysfunction has a critical role in several disorders including
      chemotherapy-induced peripheral neuropathies (CIPN). This is due to a related
      dysregulation of pathways involving calcium signalling, reactive oxygen species
      and apoptosis. Vincristine is able to affect calcium movement through the Dorsal
      Root Ganglia (DRG) neuronal mitochondrial membrane, altering its homeostasis and
      leading to abnormal neuronal excitability. Paclitaxel induces the opening of the
      mitochondrial permeability transition pore in axons followed by mitochondrial
      membrane potential loss, increased reactive oxygen species generation, ATP level
      reduction, calcium release and mitochondrial swelling. Cisplatin and oxaliplatin
      form adducts with mitochondrial DNA producing inhibition of replication,
      disruption of transcription and morphological abnormalities within mitochondria
      in DRG neurons, leading to a gradual energy failure. Bortezomib is able to modify
      mitochondrial calcium homeostasis and mitochondrial respiratory chain. Moreover,
      the expression of a certain number of genes, including those controlling
      mitochondrial functions, was altered in patients with bortezomib-induced
      peripheral neuropathy.

PMID- 29056659
TI  - Neurotoxic Effects of Platinum Compounds: Studies in vivo on Intracellular
      Calcium Homeostasis in the Immature Central Nervous System.
AB  - Platinum compounds cause significant clinical neurotoxicity. Several studies
      highlight neurological complications especially in paediatric oncology patients
      with Central Nervous System (CNS) and non-CNS malignancies. To understand the
      toxicity mechanisms of platinum drugs at cellular and molecular levels in the
      immature brain, which appears more vulnerable to injury than in the adult one, we
      compared the effects in vivo of the most used platinum compounds, i.e.,
      cisdichlorodiammineplatinum (cisplatin, cisPt), and the new [Pt(O,O'-acac)(gamma
      acac)(DMS)] (PtAcacDMS). As models of developing brain areas, we have chosen the
      cerebellum and hippocampus dentate gyrus. Both areas show the neurogenesis
      events, from proliferation to differentiation and synaptogenesis, and therefore
      allow comparing the action of platinum compounds with DNA and non-DNA targets.
      Here, we focused on the changes in the intracellular calcium homeostasis within
      CNS architecture, using two immunohistochemical markers, the calcium buffer
      protein Calbindin and Plasma Membrane Calcium ATPase. From the comparison of the
      cisPt and PtAcacDMS effects, it emerges how essential the equilibrium and synergy
      between CB and PMCA1 is or how important the presence of at least one of them is
      to warrant the morphology and function of nervous tissue and limit
      neuroarchitecture damages, depending on the peculiar and intrinsic properties of
      the developing CNS areas.

PMID- 29056661
TI  - Detection of Leptospiral DNA in the Urine of Donkeys on the Caribbean Island of
      Saint Kitts.
AB  - Leptospirosis is a global zoonosis caused by pathogenic spirochetes classified
      within the genus Leptospira. Leptospires live in the proximal renal tubules of
      reservoir or chronic carrier animals, and are shed in the urine. Naive animals
      acquire infection either when they come in direct contact with a reservoir or
      infected animals or by exposure to environmental surface water or soil that is
      contaminated with their urine. In this study, urine samples from a herd of
      donkeys on the Caribbean island of St. Kitts were screened using a TaqMan-based
      real-time quantitative polymerase chain reaction (qPCR) targeting a pathogen
      specific leptospiral gene, lipl32. Out of 124 clinically normal donkeys, 22 (18%)
      tested positive for leptospiral DNA in their urine. Water samples from two water
      troughs used by the donkeys were also tested, but were found to be free from
      leptospiral contamination. Detection of leptospiral DNA in the urine of
      clinically healthy donkeys may point to a role that these animals play in the
      maintenance of the bacteria on St. Kitts.

PMID- 29056660
TI  - In Vitro Research Tools in the Field of Human Immediate Drug Hypersensitivity and
      Their Present Use in Small Animal Veterinary Medicine.
AB  - Drug hypersensitivity reactions (DHR) are immune-mediated idiosyncratic adverse
      drug events. Type I DHR are often referred to as "immediate" and involve B
      lymphocyte-secreted IgE that bind to the membrane of basophils and mast cells,
      inducing their degranulation. This review presents various in vitro tests that
      were developed in the field of human type I HS and implemented as clinical
      diagnostic tools in human cases of immediate DHR. The respective strengths and
      weaknesses of each test will be discussed in parallel of validation data such as
      specificity and sensitivity whenever available. Some of them have also been used
      as diagnostic tools in veterinary medicine, but not in cases of immediate DHR.
      Most of these diagnostic tools can be categorized into humoral and cellular
      tests. The former tests measure serum concentrations of factors, such as
      histamine, tryptase, and drug-specific IgE. The latter assays quantify markers of
      drug-induced basophil activation or drug-specific lymphocyte proliferation.
      Pharmacogenetic markers have also been investigated in immediate DHR, but not as
      extensively as in non-immediate ones. Throughout, practical aspects and
      limitations of the tests, as well as sensitivity and specificity parameters, will
      be presented. In addition, the experience of veterinary medicine with these
      diagnostic tools will be summarized. However, to date, none of them has ever been
      reported in a veterinary case of type I DHR.

PMID- 29056663
TI  - Exposure to Photoperiod-Melatonin-Induced, Sexually-Activated Rams after Weaning
      Advances the Resumption of Sexual Activity in Post-Partum Mediterranean Ewes
      Lambing in January.
AB  - This study was aimed to determine whether the presence of sexually stimulated
      rams by photoperiodic and melatonin treatments can advance the resumption of post
      partum sexual activity in Mediterranean ewes lambing in January and weaned at the
      end of the breeding season at 41 degrees N, in March. Rams were exposed to two
      months of long days (16 h light/day) and given three melatonin implants at the
      end of the long days (sexually-activated rams; SAR). Control rams (CR) were
      exposed to the natural photoperiod. Thirty-six ewes weaned on 25 February were
      assigned to one of two groups. From 1 March to 30 June, one group was housed with
      four SAR males (SAR-treated; n = 18), and the other group (CR-treated; n = 18)
      was housed with four unstimulated rams. Ovulation was assessed once per week
      based on plasma progesterone concentrations. Estrus was monitored daily by marks
      left on ewes by rams' harnesses. SAR-treated ewes had a shorter (p < 0.01)
      weaning-first estrus interval than CR-treated ewes (61 +/- 17 days vs. 102 +/- 47
      days; mean date of first estrus after weaning on April 26 and June 6,
      respectively). The proportion of the ewes ovulating in April or May was higher (p
      < 0.05) in the SAR-treated group than in the CR-treated group. SAR-treated ewes
      resumed estrous activity sooner than CR-treated ewes such that, in April, May,
      and June, the proportion of females that exhibited estrus was higher (p < 0.01)
      in the SAR-treated group (72%, 89%, and 100%, respectively) than in the CR
      treated group (17%, 44%, and 61%, respectively). In conclusion, the introduction
      at weaning of sexually activated rams advanced the resumption of estrous activity
      in ewes in spring. The practical implications of this work could be important in
      ewes adapted for intensive production and accelerated lambing systems.

PMID- 29056664
TI  - Shape Variation in the Craniomandibular System and Prevalence of Dental Problems
      in Domestic Rabbits: A Case Study in Evolutionary Veterinary Science.
AB  - In contrast to wild lagomorphs, pet rabbits exhibit a noticeably high frequency
      of dental problems. Although dietary habits are considered as a major factor
      contributing to acquired malocclusions, the exact causes and interrelationships
      are still under debate. In this regard, an important aspect that has not been
      considered thoroughly to date is the effect of diet-induced phenotypic plasticity
      in skull morphology. Therefore, we conducted a geometric morphometric analysis on
      skull radiological images of wild and pet rabbits in order to quantify
      intraspecific variation in craniomandibular morphology. The statistical analyses
      reveal a significant morphological differentiation of the craniomandibular system
      between both groups. Furthermore, the analysis of covariance shows that the force
      generating modules (cranium and mandible) vary independently from the force
      receiving module (hypselodont teeth) in pet rabbits, which is in contrast to
      their wild relatives. Our findings suggest that the phenotypic changes in
      domestic rabbits impact mastication performance and, consequently, oral health.
      An adequate close-to-nature nutrition throughout the whole life and especially
      beginning early parallel to weaning (phase of increased phenotypic plasticity) is
      necessary to ensure a normal strain on the teeth by promoting physiological
      lateral gliding movements and avoiding direct axial loads.

PMID- 29056665
TI  - Review on Usage of Vancomycin in Livestock and Humans: Maintaining Its Efficacy,
      Prevention of Resistance and Alternative Therapy.
AB  - Vancomycin is one of the "last-line" classes of antibiotics used in the treatment
      of life-threatening infections caused by Gram-positive bacteria. Even though
      vancomycin was discovered in the 1950s, it was widely used after the 1980s for
      the treatment of infections caused by methicillin-resistant Staphylococci, as the
      prevalence of these strains were increased. However, it is currently evident that
      vancomycin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci
      have developed for various reasons, including the use of avaparcin-an analog of
      vancomycin-as a feed additive in livestock. Therefore, prophylactic and empiric
      use of antibiotics and their analogues need to be minimized. Herein we discuss
      the rational use of vancomycin in treating humans, horses, farm animals, and pet
      animals such as dogs, cats, and rabbits. In present day context, more attention
      should be paid to the prevention of the emergence of resistance to antibiotics in
      order to maintain their efficacy. In order to prevent emergence of resistance,
      proper guidance for the responsible use of antimicrobials is indispensable.
      Therefore, almost all stakeholders who use antibiotics should have an in-depth
      understanding of the antibiotic that they use. As such, it is imperative to be
      aware of the important aspects of vancomycin. In the present review, efforts have
      been made to discuss the pharmacokinetics and pharmacodynamics, indications,
      emergence of resistance, control of resistance, adverse effects, and alternative
      therapy for vancomycin.

PMID- 29056666
TI  - The Comparative Value of Feline Virology Research: Can Findings from the Feline
      Lentiviral Vaccine Be Translated to Humans?
AB  - Feline immunodeficiency virus (FIV) is a lentivirus of domestic cats that shares
      several similarities with its human counterpart, human immunodeficiency virus
      (HIV). Their analogies include genomic organization, lymphocyte tropism, viral
      persistence and induction of immunodeficiency. FIV is the only lentivirus for
      which a commercial vaccine is registered for prevention in either human or
      veterinary medicine. This provides a unique opportunity to investigate the
      mechanisms of protection induced by lentivirus vaccines at the population level
      and might contribute to the development of efficacious HIV vaccines. As well as
      having comparative value for vaccine studies, FIV research has shed some light on
      the relationship between lentiviral tropism and pathogenesis. Recent studies in
      our laboratory demonstrated that the interaction between FIV and its primary
      receptor changes as disease progresses, reminiscent of the receptor switch
      observed as disease progresses in HIV infected individuals. Here we summarise
      findings illustrating that, in addition to its veterinary significance, FIV has
      comparative value, providing a useful model to explore lentivirus-host
      interactions and to examine potential immune correlates of protection against HIV
      infection.

PMID- 29056667
TI  - Hyponatremia as the Presenting Feature of a Pituitary Abscess in a Calf.
AB  - A 2-month-old Simmental heifer presented for acute onset of neurological
      behavior. Laboratory tests confirmed the presence of hyponatremia, hypochloremia,
      and hypokalemia that improved with intravenous fluid therapy. Despite an initial
      cessation of neurological signs, symptoms re-emerged, and the heifer was
      euthanized due to poor prognosis. A pituitary abscess (Trueperella pyogenes) was
      observed on gross necropsy, suggesting that the effects of panhypopituitarism
      (inappropriate anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH),
      and/or thyroid-stimulating hormone (TSH) secretion) may have resulted in the
      clinical findings. Pituitary abscess syndrome carries a poor prognosis due to the
      inability to penetrate the area with systemic antibiotic therapy. These findings
      highlight the unusual clinical presentations that may occur following pituitary
      abscess syndrome in cattle that practitioners need to consider when determining
      prognosis.

PMID- 29056668
TI  - Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs.
AB  - Physical activity is dependent upon the cardiovascular system adequately
      delivering blood to meet the metabolic and thermoregulatory demands of exercise.
      Animals who regularly exercise therefore require a well-adapted heart to support
      this delivery. The purpose of this review is to examine cardiac structure, and
      the potential for exercise-induced cardiac remodeling, in animals that regularly
      engage in strenuous activity. Specifically, we draw upon the literature that has
      studied the "athlete's heart" in humans, horses, and dogs, to enable the reader
      to compare and contrast cardiac remodeling in these three athletic species. The
      available literature provides compelling evidence for exercise-induced cardiac
      remodeling in all three species. However, more work is required to understand the
      influence of species/breed specific genetics and exercise-related hemodynamics,
      in order to fully understand the impact of exercise on cardiac structure.

PMID- 29056669
TI  - Metastatic Squamous Cell Carcinoma in a Northern Brown Bandicoot (Isoodon
      macrourus).
AB  - Aside from a handful of notable exceptions, neoplasia is not reported as a major
      cause of mortality in wild animal populations and often goes undetected. For
      northern brown bandicoots specifically, there are few reported tumors in the
      literature and on file in the Australian Registry of Wildlife Health. This report
      describes a case of squamous cell carcinoma in a northern brown bandicoot
      (Isoodon macrourus), with metastases to the draining lymph nodes and lung. This
      neoplasm consisted predominantly of well-differentiated squamous cells and
      multifocal keratin pearls, with areas possibly consistent with epithelial to
      mesenchymal transition, as identified by positive immunohistochemical staining by
      both pancytokeratin (AE1/AE3) and vimentin. Additional investigations were
      negative for bandicoot papillomatosis carcinomatosis viruses.

PMID- 29056671
TI  - Micro-RNA 10a Is Increased in Feline T Regulatory Cells and Increases Foxp3
      Protein Expression Following In Vitro Transfection.
AB  - CD4+CD25+Foxp3+ T regulatory (Treg) cells are activated during the course of
      lentiviral infection and exhibit heightened suppressor function when compared to
      Treg cells from uninfected controls. Foxp3 is essential to Treg cell function and
      multiple studies have documented that lentivirus-activated Treg cells exhibit
      heightened Foxp3 expression when compared to Treg cells from uninfected controls.
      Our hypothesis was that lentivirus-induced micro-RNAs (miRNAs) contribute to
      heightened Treg cell suppressor function by stabilizing Foxp3 expression. We
      demonstrated that CD4+CD25+ T cells from both feline immunodeficiency virus
      infected (FIV+) cats and uninfected control cats exhibit increased miRNA 10a and
      21 levels compared to autologous CD4+CD25- T cells but there was no difference in
      the levels of these miRNAs when Treg cells from FIV+ cats were compared to Treg
      cells from uninfected controls. Further, there was no increase in Foxp3 mRNA
      following transfection of miRNA 10a or 21 into a feline cell line. However,
      transfection with miRNA 10a resulted in increased Foxp3 protein expression.

PMID- 29056670
TI  - Protein Composition of the Bovine Herpesvirus 1.1 Virion.
AB  - Bovine herpesvirus (BoHV) type 1 is an important agricultural pathogen that
      infects cattle and other ruminants worldwide. Acute infection of the oro
      respiratory tract leads to immune suppression and allows commensal bacteria to
      infect an otherwise healthy lower respiratory tract. This condition is known as
      the Bovine Respiratory Disease (BRD). BoHV-1 latently infects the host for life
      and periodical stress events re-initiate BRD, translating into high morbidity and
      large economic losses. To gain a better understanding of the biology of BoHV-1
      and the disease it causes, we elucidated the protein composition of extracellular
      virions using liquid chromatography-mass spectrometry analysis. We detected 33
      viral proteins, including the expected proteins of the nucleocapsid and envelope
      as well as other regulatory proteins present in the viral tegument. In addition
      to viral proteins, we have also identified packaged proteins of host origin. This
      constitutes the first proteomic characterization of the BoHV virion.

PMID- 29056672
TI  - Immuno-Detection of C3a, a C3 Complement Activated Product in Mastitis Milk, a
      Potential Diagnostic Marker.
AB  - The sub-clinical form of mastitis is difficult to detect and causes huge economic
      loss to the dairy industry. It has become a threat to public health at large,
      thus there is a need for definite diagnosis of the disease. Therefore, this study
      was undertaken to identify the novel diagnostic marker for the detection of the
      sub-clinical form of mastitis. Two-dimensional gel analysis of the whey protein
      fraction of normal and mastitis milk samples revealed the presence of proteose
      peptone component 3 precursor, Trypsin precursor, complement component-C3, Ig
      heavy chain precursors and a C-type lectin domain as differentially expressed
      protein during the early stage of mastitis. Of these proteins identified,
      complement component-C3 was tested for its diagnostic potential. Western blot
      analysis of the milk whey of sub-clinical mastitis cases (M+, M++ & M+++)
      identified the accumulation of C3a, an activated product of complement component
      C3. Further, the hemolytic activity of the above milk whey samples positively
      correlated with the somatic cell count. As C3a is already reported as an
      anaphylotoxic agent, it chemo tactically attracts lymphocytes at the site of
      inflammation, the detection of which in the milk whey can be of diagnostic
      importance for sub-clinical mastitis.

PMID- 29056674
TI  - The Awareness of the International Veterinary Profession of Evidence-Based
      Veterinary Medicine and Preferred Methods of Training.
AB  - Evidence-based veterinary medicine (EVM) is an evolving discipline in veterinary
      medicine so it is important to periodically "benchmark" opinion about EVM across
      the profession. An international survey to assess veterinarians' awareness of EVM
      was conducted. Veterinarians were surveyed via an online questionnaire (all
      countries) or a postal questionnaire (UK only). Participants were asked whether
      they had heard of EVM, where they had first heard the term, and their preferences
      of method for receiving continuing professional development (CPD). There were
      6310 respondents, of which 4579 (72.5%) worked in the UK and 5384 (85.3%) were
      clinicians. Veterinarians that had heard of EVM (n = 5420, 85.9%) were most
      likely to be clinicians (OR = 4.00; 95% CI: 3.37, 4.75), respondents working in
      the UK (OR = 1.32; CI: 1.13, 1.54), or respondents with a postgraduate degree or
      qualification (OR = 1.77; CI: 1.51, 2.08). The most common sources from which
      respondents had heard of EVM were at vet school or university (n = 1207, 29.8%),
      via literature (peer-reviewed papers or other publications) (n = 1074, 26.5%),
      and via CPD courses (n = 564, 13.9%). Most respondents were interested in finding
      out more about EVM (n = 4256 of 6173, 69%). The preferred methods of CPD were day
      or evening seminars (n = 2992 of 6017, 49.7%), conferences (n = 1409, 23.4%), and
      online courses (n = 524, 8.7%), although the order of preference differed
      slightly between groups. There appears to be substantial awareness of EVM amongst
      veterinarians internationally. However, it appears that further training in EVM
      would be welcomed. Preferences on how CPD in general is received differs between
      groups, so this should be borne in mind by training providers when formulating a
      strategy for the dissemination of EVM training across the global profession.

PMID- 29056675
TI  - Felis Catus Gammaherpesvirus 1 DNAemia in Whole Blood from Therapeutically
      Immunosuppressed or Retrovirus-Infected Cats.
AB  - Gammaherpesviruses are major co-pathogens of human immunodeficiency virus (HIV)
      infection, making the interactions between feline immunodeficiency virus (FIV)
      and Felis catus gammaherpesvirus 1 (FcaGHV1) pertinent to both human and
      veterinary medical research. FIV-infected cats are at increased risk of FcaGHV1
      DNAemia and consistently harbor higher FcaGHV1 loads than FIV-uninfected cats.
      Whether immune deficiencies unrelated to FIV are associated with similar risks is
      unknown. Using whole blood FcaGHV1 qPCR, we found no difference in the frequency
      of DNAemia or DNA load in therapeutically immunosuppressed (P1, n = 18) or feline
      leukemia virus (FeLV)-infected (P2, n = 57) patients compared with age- and sex
      matched controls (C1, n = 58; C2, n = 57). In contrast, FIV/FeLV-co-infected cats
      (P3, n = 5) were at increased risk of FcaGHV1 DNAemia compared to retrovirus
      uninfected controls (C3, n = 39; p = 0.0068), and had a higher median FcaGHV1 DNA
      load, although the latter was not significant. FIV/FeLV-co-infected cats (P3) had
      a similar frequency of FcaGHV1 DNAemia reported compared to FIV-infected controls
      (C4). In conclusion, we found no evidence that cats with therapeutic
      immunosuppression or FeLV infection were at greater risk of FcaGHV1 DNAemia or
      had higher FcaGHV1 DNA load in whole blood. The risk of DNAemia in FIV/FeLV-co
      infected cats was similar to that documented previously in cats infected with FIV
      alone.

PMID- 29056673
TI  - Feline Immunodeficiency Virus Neuropathogenesis: A Model for HIV-Induced CNS
      Inflammation and Neurodegeneration.
AB  - Feline Immunodeficiency virus (FIV), similar to its human analog human
      immunodeficiency virus (HIV), enters the central nervous system (CNS) soon after
      infection and establishes a protected viral reservoir. The ensuing inflammation
      and damage give rise to varying degrees of cognitive decline collectively known
      as HIV-associated neurocognitive disorders (HAND). Because of the similarities to
      HIV infection and disease, FIV has provided a useful model for both in vitro and
      in vivo studies of CNS infection, inflammation and pathology. This mini review
      summarizes insights gained from studies of early infection, immune cell
      trafficking, inflammation and the mechanisms of neuropathogenesis. Advances in
      our understanding of these processes have contributed to the development of
      therapeutic interventions designed to protect neurons and regulate inflammatory
      activity.

PMID- 29056676
TI  - Serum Fructosamine Concentration in Uncontrolled Hyperthyroid Diabetic Cats Is
      within the Population Reference Interval.
AB  - Diabetes mellitus is a common endocrinopathy of cats that is characterized by
      persistent fasting hyperglycemia. However, stress induces substantial
      hyperglycemia in cats that poses a challenge to the veterinarian who may wrongly
      interpret the high serum concentration of blood glucose as evidence of diabetes
      mellitus. Fructosamine is a glycated serum protein that serves as an index of
      glycemic control in cats and is useful because it is not affected by stress
      hyperglycemia. However, factors such as body weight, hypoproteinemia, and
      increased serum thyroid hormone concentration can alter fructosamine
      concentration. The goal of this retrospective study was to compare the
      fructosamine concentrations in diabetic and nondiabetic cats with and without
      uncontrolled hyperthyroidism. A secondary goal was to determine the effect of
      sex, age, different populations of cats, and diabetes on the variability of
      fructosamine. We found that the mean (+/-SE) serum fructosamine of hyperthyroid
      diabetic cats (332 +/- 24 umol/L, 95% CI 291-379 umol/L) was within the
      population-based reference interval (200-360 umol/L) and significantly lower in
      comparison to euthyroid diabetic cats (527 +/- 10 umol/L, 95% CI 515-553 umol/L).
      Additionally, in this study, diabetes accounted only for approximately 50% of the
      variance in serum fructosamine, while age, sex, and population made a minor
      contribution to this variance. In conclusion, finding serum fructosamine that is
      within the population-based reference interval in an uncontrolled diabetic cat
      should alert the veterinarian to the possibility of concurrent hyperthyroidism.
      Additionally, the veterinary clinician should consider that serum fructosamine
      might be substantially affected by factors other than diabetes.

PMID- 29056677
TI  - Effect of Oral Alpha Lipoic Acid in Preventing the Genesis of Canine Diabetic
      Cataract: A Preliminary Study.
AB  - Blinding cataract is a significant effect of canine diabetes with 75% of animals
      affected two years after diagnosis. Lens opacification occurs primarily through
      the generation of sorbitol, a sugar alcohol, through the action of aldose
      reductase (AR). The osmotic effect of sorbitol draws water into the lens, causing
      opacification. Inhibition of AR should thus prevent the generation of cataracts.
      A topical AR inhibitor has been shown to have this effect, as has the
      commercially available neutraceutical OcuGLO, containing the AR inhibitor alpha
      lipoic acid (ALA) together with other plant-based antioxidants. Here a comparison
      is made between the number of diabetic dogs developing cataracts when given oral
      ALA alone and those given a mix containing ascorbic acid and tocopherol. Animals
      given ALA developed significantly fewer lens opacities than those given
      conventional antioxidants. Cataracts which formed occurred at a significantly
      greater duration after the commencement of treatment than those on the
      antioxidant mix. Although this is a small study conducted over a short period,
      the significant benefit of ALA in diabetic dogs is a reason to evaluate these
      effects in larger trials. As AR is involved in diabetic retinopathy and
      neuropathy, this enzyme inhibitor may be worthy of evaluation in preventing these
      conditions in human diabetics also.

PMID- 29056679
TI  - Coronary Artery Anomalies in Animals.
AB  - Coronary artery anomalies represent a disease spectrum from incidental to life
      threatening. Anomalies of coronary artery origin and course are well-recognized
      in human medicine, but have received limited attention in veterinary medicine.
      Coronary artery anomalies are best described in the dog, hamster, and cow though
      reports also exist in the horse and pig. The most well-known anomaly in
      veterinary medicine is anomalous coronary artery origin with a prepulmonary
      course in dogs, which limits treatment of pulmonary valve stenosis. A
      categorization scheme for coronary artery anomalies in animals is suggested,
      dividing these anomalies into those of major or minor clinical significance. A
      review of coronary artery development, anatomy, and reported anomalies in
      domesticated species is provided and four novel canine examples of anomalous
      coronary artery origin are described: an English bulldog with single left
      coronary ostium and a retroaortic right coronary artery; an English bulldog with
      single right coronary ostium and transseptal left coronary artery; an English
      bulldog with single right coronary ostium and absent left coronary artery with a
      prepulmonary paraconal interventricular branch and an interarterial circumflex
      branch; and a mixed-breed dog with tetralogy of Fallot and anomalous origin of
      all coronary branches from the brachiocephalic trunk. Coronary arterial fistulae
      are also described including a coronary cameral fistula in a llama cria and an
      English bulldog with coronary artery aneurysm and anomalous shunting vessels from
      the right coronary artery to the pulmonary trunk. These examples are provided
      with the intent to raise awareness and improve understanding of such defects.

PMID- 29056678
TI  - Genomic Insights into Cardiomyopathies: A Comparative Cross-Species Review.
AB  - In the global human population, the leading cause of non-communicable death is
      cardiovascular disease. It is predicted that by 2030, deaths attributable to
      cardiovascular disease will have risen to over 20 million per year. This review
      compares the cardiomyopathies in both human and non-human animals and identifies
      the genetic associations for each disorder in each species/taxonomic group.
      Despite differences between species, advances in human medicine can be gained by
      utilising animal models of cardiac disease; likewise, gains can be made in animal
      medicine from human genomic insights. Advances could include undertaking regular
      clinical checks in individuals susceptible to cardiomyopathy, genetic testing
      prior to breeding, and careful administration of breeding programmes (in non
      human animals), further development of treatment regimes, and drugs and
      diagnostic techniques.

PMID- 29056681
TI  - Minimising Stress for Patients in the Veterinary Hospital: Why It Is Important
      and What Can Be Done about It.
AB  - Minimising stress for patients should always be a priority in the veterinary
      hospital. However, this is often overlooked. While a "no stress" environment is
      not possible, understanding how to create a "low stress" (sometimes called "fear
      free") environment and how to handle animals in a less stressful manner benefits
      patients, staff and the hospital alike. Many veterinary practitioners believe
      creating a low stress environment is too hard and too time consuming, but this
      need not be the case. With some simple approaches, minimising patient, and hence
      staff, stress is achievable in all veterinary practices. This article provides a
      background on why minimising stress is important and outlines some practical
      steps that can be taken by staff to minimise stress for presenting and
      hospitalised patients. Useful resources on recognising signs of stress in dogs
      and cats, handling, restraint, behaviour modification, medications, and hospital
      design are provided.

PMID- 29056680
TI  - Animal Models of Cancer-Associated Hypercalcemia.
AB  - Cancer-associated hypercalcemia (CAH) is a frequently-occurring paraneoplastic
      syndrome that contributes to substantial patient morbidity and occurs in both
      humans and animals. Patients with CAH are often characterized by markedly
      elevated serum calcium concentrations that result in a range of clinical symptoms
      involving the nervous, gastrointestinal and urinary systems. CAH is caused by two
      principle mechanisms; humorally-mediated and/or through local osteolytic bone
      metastasis resulting in excessive calcium release from resorbed bone. Humoral
      hypercalcemia of malignancy (HHM) is the most common mechanism and is due to the
      production and release of tumor-associated cytokines and humoral factors, such as
      parathyroid hormone-related protein (PTHrP), that act at distant sites to
      increase serum calcium concentrations. Local osteolytic hypercalcemia (LOH)
      occurs when primary or metastatic bone tumors act locally by releasing factors
      that stimulate osteoclast activity and bone resorption. LOH is a less frequent
      cause of CAH and in some cases can induce hypercalcemia in concert with HHM.
      Rarely, ectopic production of parathyroid hormone has been described. PTHrP
      mediated hypercalcemia is the most common mechanism of CAH in human and canine
      malignancies and is recognized in other domestic species. Spontaneous and
      experimentally-induced animal models have been developed to study the mechanisms
      of CAH. These models have been essential for the evaluation of novel approaches
      and adjuvant therapies to manage CAH. This review will highlight the comparative
      aspects of CAH in humans and animals with a discussion of the available animal
      models used to study the pathogenesis of this important clinical syndrome.

PMID- 29056682
TI  - Mapping Heart Development in Flies: Src42A Acts Non-Autonomously to Promote Heart
      Tube Formation in Drosophila.
AB  - Congenital heart defects, clinically identified in both small and large animals,
      are multifactorial and complex. Although heritable factors are known to have a
      role in cardiovascular disease, the full genetic aetiology remains unclear. Model
      organism research has proven valuable in providing a deeper understanding of the
      essential factors in heart development. For example, mouse knock-out studies
      reveal a role for the Integrin adhesion receptor in cardiac tissue. Recent
      research in Drosophila melanogaster (the fruit fly), a powerful experimental
      model, has demonstrated that the link between the extracellular matrix and the
      cell, mediated by Integrins, is required for multiple aspects of cardiogenesis.
      Here we test the hypothesis that Integrins signal to the heart cells through
      Src42A kinase. Using the powerful genetics and cell biology analysis possible in
      Drosophila, we demonstrate that Src42A acts in early events of heart tube
      development. Careful examination of mutant heart tissue and genetic interaction
      data suggests that Src42A's role is independent of Integrin and the Integrin
      related Focal Adhesion Kinase. Rather, Src42A acts non-autonomously by promoting
      programmed cell death of the amnioserosa, a transient tissue that neighbors the
      developing heart.

PMID- 29056684
TI  - Cutaneous Hypersensitivity Dermatoses in the Feline Patient: A Review of Allergic
      Skin Disease in Cats.
AB  - Feline allergic skin disease presents a unique set of challenges to the
      veterinary practitioner. Although there is some similarity to what is seen in the
      allergic canine patient, cutaneous hypersensitivity dermatoses in cats can
      manifest with strikingly different clinical signs, treatment options and
      outcomes, and secondary complications/disease entities. Additionally, less is
      known about the pathogenesis of feline allergic skin diseases, particularly
      "feline atopic syndrome" when compared to dogs or people. This article aims to
      review what is currently known in regards to allergic skin disease in the feline
      patient, with focus on non-flea, non-food hypersensitivity dermatitis.

PMID- 29056685
TI  - Prevalence and Multilocus Genotyping Analysis of Cryptosporidium and Giardia
      Isolates from Dogs in Chiang Mai, Thailand.
AB  - The occurrence and zoonotic potential of Cryptosporidium spp. and Giardia
      duodenalis isolated from dogs in Chiang Mai, Thailand were determined. Fecal
      samples were collected from 109 dogs between July and August 2008.
      Cryptosporidium spp. infection was determined by immunofluorescent assay (IFA),
      PCR assays that amplify Cryptosporidium heat-shock protein 70 kDa (hsp70), and
      two PCR assays that amplify a small subunit-ribosomal RNA (SSU-rRNA).
      Giardiaduodenalis infection was identified using zinc sulfate centrifugal
      flotation, IFA, and four PCR assays that amplify the Giardia glutamate
      dehydrogenase (gdh), beta-giardin (bg), and generic and dog-specific assays of
      triosephosphate isomerase (tpi) genes. Overall prevalence of Cryptosporidium spp.
      and G.duodenalis was 31.2% and 45.9%, respectively. Sequence analysis of 22
      Cryptosporidium-positive samples and 21 Giardia-positive samples revealed the
      presence of C.canis in 15, and C. parvum in 7, G. duodenalis Assemblage C in 8, D
      in 11, and mixed of C and D in 2 dogs. Dogs in Chiang Mai were commonly exposed
      to Cryptosporidium spp. and G. duodenalis. Cryptosporidium parvum can be isolated
      from the feces of dogs, and all G. duodenalis assemblages were dog-specific. Dogs
      could be a reservoir for a zoonotic Cryptosporidium infection in humans, but
      further studies will be required to determine the clinical and zoonotic
      importance.

PMID- 29056686
TI  - The Big Pet Diabetes Survey: Perceived Frequency and Triggers for Euthanasia.
AB  - Current pet diabetes mellitus (DM) treatment necessitates the active daily
      involvement of owners and can be costly. The current study aimed to investigate
      the owner population which opts for euthanasia instead of DM treatment. A survey
      was designed using multiple feedback steps and made available online to
      veterinarians world-wide. A total of 1192 veterinarians completed the survey and
      suggested a median one in 10 diabetic pets are euthanased at diagnosis; a further
      median one in 10 within one year because of lack of success or compliance.
      Perceived most important motivating factors included "presence concurrent
      disease" (45% respondents); "costs" (44%); "animal age" (37%); "problems
      obtaining adequate control" (35%); "pet welfare" (35%); and "impact owner's
      lifestyle" (32%). Cats in Canadian (odds ratio (OR) 2.7), Australian (OR 2.3),
      rural (OR 1.6) and mixed (OR 1.7) practices were more likely to be euthanased
      because of DM diagnosis, while cats presented to referral/university were less
      likely to be euthanased (OR 0.6). Dogs were more likely to be euthanased because
      of DM in Canadian (OR 1.8), rural (OR 1.8) and mixed (OR 1.6) practices. The
      survey results suggest that benefit exists in improved DM education with emphasis
      on offering a choice of treatment styles ranging from intense and expensive to
      hands-off and cheap.

PMID- 29056683
TI  - Dissecting the Role of the Extracellular Matrix in Heart Disease: Lessons from
      the Drosophila Genetic Model.
AB  - The extracellular matrix (ECM) is a dynamic scaffold within organs and tissues
      that enables cell morphogenesis and provides structural support. Changes in the
      composition and organisation of the cardiac ECM are required for normal
      development. Congenital and age-related cardiac diseases can arise from mis
      regulation of structural ECM proteins (Collagen, Laminin) or their receptors
      (Integrin). Key regulators of ECM turnover include matrix metalloproteinases
      (MMPs) and their inhibitors, tissue inhibitors of matrix metalloproteinases
      (TIMPs). MMP expression is increased in mice, pigs, and dogs with cardiomyopathy.
      The complexity and longevity of vertebrate animals makes a short-lived,
      genetically tractable model organism, such as Drosophila melanogaster, an
      attractive candidate for study. We survey ECM macromolecules and their role in
      heart development and growth, which are conserved between Drosophila and
      vertebrates, with focus upon the consequences of altered expression or
      distribution. The Drosophila heart resembles that of vertebrates during early
      development, and is amenable to in vivo analysis. Experimental manipulation of
      gene function in a tissue- or temporally-regulated manner can reveal the function
      of adhesion or ECM genes in the heart. Perturbation of the function of ECM
      proteins, or of the MMPs that facilitate ECM remodelling, induces
      cardiomyopathies in Drosophila, including cardiodilation, arrhythmia, and cardia
      bifida, that provide mechanistic insight into cardiac disease in mammals.

PMID- 29056687
TI  - The Epidemiology of Q Fever in England and Wales 2000-2015.
AB  - Between 2000 and 2015, 904 cases of acute Q fever were reported in England and
      Wales. The case dataset had a male to female ratio of 2.5:1, and a median age of
      45 years. Two outbreaks were recognised during this time period, and the
      incidence of sporadic cases was highest across the southwest of England, and
      Wales. There are limitations in the surveillance system for Q fever, including
      possible geographical differences in reporting and limited epidemiological data
      collection. The surveillance system needs to be strengthened in order to improve
      the quality and completeness of the epidemiological dataset. The authors conclude
      with recommendations on how to achieve this.

PMID- 29056688
TI  - A Retrospective Cohort Study of an Outbreak of Cryptosporidiosis among Veterinary
      Students.
AB  - An outbreak of gastrointestinal illness occurred among a cohort of 56 veterinary
      technology and 100 veterinary science students at Massey University over an eight
      week period in 2013. This coincided with calving in New Zealand's seasonal dairy
      farming system and a time when calves with diarrhoea are commonly seen by
      veterinarians. Laboratory and epidemiological investigations were instigated by
      MidCentral Public Health Service (MCPHS) in conjunction with the Institute of
      Veterinary, Animal and Biomedical Sciences (IVABS) at Massey University. Eighty
      students responded to a questionnaire of which 19 met the case definition, a 24%
      attack rate. Faecal specimens from seven students contained Cryptosporidium
      oocysts and Cryptosporidium parvum IIa A18G3R1 was identified from one of the
      specimens. The inferred median incubation period was five days (range 1-12 days).
      All of the cases were self-limiting, characterized by diarrhoea, abdominal
      cramps, and in some cases vomiting, headache, and fever. Having contact with
      calves with diarrhoea was significantly associated with increased adjusted odds
      of being a case (OR 10.61, 95% CI 1.87-108.29 for one week of contact; OR 55.05,
      95% CI 3.80-1931.18 for two weeks of contact). Outbreaks of cryptosporidiosis had
      occurred previously among veterinary students at Massey University, but the
      extremely high infectivity of C. parvum resulted in student illness despite
      enhanced hygiene precautions.

PMID- 29056689
TI  - Inaccurate Assessment of Canine Body Condition Score, Bodyweight, and Pet Food
      Labels: A Potential Cause of Inaccurate Feeding.
AB  - The objectives were to investigate owners' ability to assign the correct
      bodyweight (BW) and body condition score (BCS) to their dog and to interpret wet
      and dry pet food labels by estimating how much to feed daily. One hundred and
      seventy-four questionnaires were completed. Owner estimated BW was compared to
      actual BW, correct being defined within +/-10% of actual BW. Correct
      interpretation of the total amount of food required was determined by the number
      of cans (+/-25% of cans) required for wet food and grams (+/-20% of grams) for
      dry food, based on the dog's actual BW, the feeding guidelines on the label, and
      a comparison with the owner's estimate. Eleven percent of owners overestimated
      BCS and 19% overestimated BW. Only 48% of owners could correctly estimate their
      dog's BW. Only 23% and 43% of owners could correctly estimate how much wet and
      dry food to feed, respectively. Chi-square analysis demonstrated a significant
      positive association for owners correctly estimating their dog's BW and
      interpreting the wet pet food label. Many owners are not aware of their pet's BCS
      and BW and cannot accurately interpret pet food labels. Further owner education
      to improve these skills is needed if dogs are to be fed correctly.

PMID- 29056690
TI  - Detection and Characterization of Histamine-Producing Strains of Photobacterium
      damselae subsp. damselae Isolated from Mullets.
AB  - Photobacterium damselae subsp. damselae (Pdd) is considered to be an emerging
      pathogen of marine fish and has also been implicated in cases of histamine food
      poisoning. In this study, eight strains isolated from mullets of the genera Mugil
      and Liza captured in the Ligurian Sea were characterized, and a method to detect
      histamine-producing Pdd from fish samples was developed. The histamine-producing
      potential of the strains was evaluated in culture media (TSB+) using a histamine
      biosensor. Subsequently, two strains were used to contaminate mackerel fillets (4
      or 40 CFU/g), simulating a cross-contamination on the selling fish stalls. Sample
      homogenates were enriched in TSB+. The cultures were then inoculated on
      thiosulfate-citrate-bile salts-sucrose agar (TCBS) and the dark green colonies
      were cultured on Niven agar. The violet isolates were characterized using
      specific biochemical and PCR based tests. All Pdd strains were histamine
      producers, yielding concentration varying from 167 and 8977 ug/mL in TSB+
      cultures incubated at 30  degrees C for 24 h. Pdd colonies were detected from the
      inoculated mackerel samples and their histidine decarboxylase gene was amplified
      using species-specific primer pairs designed for this study. The results indicate
      that mullets can be source of Pdd and the fish retailers needs to evaluate the
      risk posed by cross-contamination on the selling fish stalls.

PMID- 29056691
TI  - Comparative Studies in Tick-Borne Diseases in Animals and Humans.

PMID- 29056692
TI  - Raw Meat-Based Diets in Dogs and Cats.
AB  - Feeding pets raw meat-based diets (RMBDs) is commonly practiced by many companion
      animal owners and has received increasing attention in recent years. It may be
      beneficial for the animals, but may also pose a health risk for both pets and
      their owners, as RMBDs may be contaminated by enteric pathogens-such as
      Campylobacter, Salmonella, and Yersinia-which are the most common zoonotic
      bacteria causing enteritis in humans. Little information exists on the prevalence
      of these pathogens in pet food, and thus one aim was to investigate the
      prevalence of Campylobacter, Salmonella, and Yersinia in commercial RMBDs from
      retail stores. Little evidence also exists on the significance of raw meat
      feeding on the shedding of Campylobacter, Salmonella, and enteropathogenic
      Yersinia in the feces of pets, and therefore, the second goal was to study the
      presence of these pathogens in dogs and cats fed RMBDs. Polymerase chain reaction
      (PCR) only sporadically detected Campylobacter, Salmonella, and enteropathogenic
      Yersinia in RMBDs. These pathogens were not found by culturing, indicating a low
      contamination level in frozen RMBDs. They were also detected in the feces of dogs
      and cats, but the association with feeding RMBDs to them remained unclear.

PMID- 29056693
TI  - Comparative Transcriptomic Profiling and Gene Expression for Myxomatous Mitral
      Valve Disease in the Dog and Human.
AB  - Myxomatous mitral valve disease is the single most important mitral valve disease
      in both dogs and humans. In the case of the dog it is ubiquitous, such that all
      aged dogs will have some evidence of the disease, and for humans it is known as
      Barlow's disease and affects up to 3% of the population, with an expected
      increase in prevalence as the population ages. Disease in the two species show
      many similarities and while both have the classic myxomatous degeneration only in
      humans is there extensive fibrosis. This dual pathology of the human disease
      markedly affects the valve transcriptome and the difference between the dog and
      human is dominated by changes in genes associated with fibrosis. This review will
      briefly examine the comparative valve pathology and then, in more detail, the
      transcriptomic profiling and gene expression reported so far for both species.

PMID- 29056694
TI  - Inquiring into the Gaps of Campylobacter Surveillance Methods.
AB  - Campylobacter is one of the most common pathogen-related causes of diarrheal
      illnesses globally and has been recognized as a significant factor of human
      disease for more than three decades. Molecular typing techniques and their
      combinations have allowed for species identification among members of the
      Campylobacter genus with good resolution, but the same tools usually fail to
      proceed to subtyping of closely related species due to high sequence similarity.
      This problem is exacerbated by the demanding conditions for isolation and
      detection from the human, animal or water samples as well as due to the
      difficulties during laboratory maintenance and long-term storage of the isolates.
      In an effort to define the ideal typing tool, we underline the strengths and
      limitations of the typing methodologies currently used to map the broad
      epidemiologic profile of campylobacteriosis in public health and outbreak
      investigations. The application of both the old and the new molecular typing
      tools is discussed and an indirect comparison is presented among the preferred
      techniques used in current research methodology.

PMID- 29056695
TI  - Myocardial Adiponectin Isoform Shift in Dogs with Congestive Heart Failure-A
      Comparison to Hibernating Brown Bears (Ursus arctos horribilis).
AB  - Adiponectin is the most abundant plasma adipokine, and is well known for its role
      in energy homeostasis and cardiac protection. In humans with dilated
      cardiomyopathy, myocardial adiponectin protein expression is reduced compared to
      normal hearts and has been implicated in the pathology of cardiomyopathy. Serum
      adiponectin levels are often conflicting, with higher levels associated with poor
      survival in humans with congestive heart failure (CHF). We evaluated adiponectin
      serum concentrations and myocardial protein expression in dogs with naturally
      occurring myxomatous mitral valve disease and CHF. We compared the findings to
      active and hibernating brown bears as bears are adapted to endure an extreme
      period of low cardiac output during their annual hibernation. Bears exhibited
      largely the active high-molecular weight (HMW) versus the low-molecular weight
      isoforms of myocardial adiponectin (HMW:LMW = 6.3) during both the active period
      and hibernation, while healthy dogs exhibited a more balanced mix of isoforms.
      Dogs with CHF expressed predominately HMW isoforms of adiponectin (HMW:LMW =
      12.5), appearing more similar to bears. In contrast to humans, serum adiponectin
      was significantly lower in dogs with CHF and lowest levels in the severest CHF
      class. In both dogs and bears, myocardial adiponectin was expressed independent
      of circulating adiponectin concentrations, suggesting a local regulatory
      mechanism within the heart.

PMID- 29056696
TI  - Atopic Dermatitis in Animals and People: An Update and Comparative Review.
AB  - Atopic dermatitis is an extremely common, pruritic, and frustrating disease to
      treat in both people and animals. Atopic dermatitis is multifactorial and results
      from complex interactions between genetic and environmental factors. Much
      progress has been done in recent years in terms of understanding the complex
      pathogenesis of this clinical syndrome and the identification of new treatments.
      As we learn more about it, we appreciate the striking similarities that exist in
      the clinical manifestations of this disease across species. Both in animals and
      people, atopic disease is becoming increasingly common and important similarities
      exist in terms of immunologic aberrations and the propensity for allergic
      sensitization. The purpose of this review is to highlight the most recent views
      on atopic dermatitis in both domestic species and in people emphasizing the
      similarities and the differences. A comparative approach can be beneficial in
      understanding the natural course of this disease and the variable response to
      existing therapies.

PMID- 29056698
TI  - Correlation between Preoperative Ultrasonographic Findings and Clinical,
      Intraoperative, Cytopathological, and Histopathological Diagnosis of Acute
      Abdomen Syndrome in 50 Dogs and Cats.
AB  - Acute abdomen syndrome is an emergency in small animal practice that requires
      rapid diagnosis to determine the appropriate treatment. No studies have
      correlated the preoperative abdominal ultrasonography (US) findings with the
      clinical, surgical, cytopathologic, and histopathologic findings. This
      retrospective study was designed to evaluate abdominal US in the diagnosis of
      acute abdomen syndrome using surgery as a "criterion standard". The most
      frequently misinterpreted lesions with US were also identified. The study
      included 50 dogs and cats with physical examination, an US diagnosis, US guided
      fine-needle aspiration cytology, intraoperative findings, and histopathology.
      Intraoperatively, 49 primary and 43 secondary lesions were identified. The
      sensitivity, specificity, and positive and negative predictive values for US were
      calculated. There was a good agreement between the US diagnosis and
      intraoperative findings of 86.9% (80/92), for both primary and secondary lesions
      (p < 0.0001). Cytology and histopathology examinations corroborated the US in
      86.4% (n = 64/74) of primary and 66.2% of secondary (n = 49/79) lesions. Using US
      as the "criterion standard", the sensitivity of abdominal palpation for
      identification of ascites and masses was 32.4% and 43.7%, respectively, while the
      specificity was 93.7% and 94.4%, respectively. Abdominal US is a useful
      preoperative modality for diagnosing acute abdominal diseases in dogs and cats.
      Care should be taken with interpretation of gastrointestinal perforation, omental
      tumors, and common bile duct rupture, as these lesions are frequently
      misinterpreted with US.

PMID- 29056697
TI  - Respiratory Allergens from Furred Mammals: Environmental and Occupational
      Exposure.
AB  - Furry mammals kept as pets, farm and laboratory animals are important allergen
      sources. The prevalence of sensitization to furred mammals appears to be
      increasing worldwide. Several mammalian allergens from diverse species are well
      characterized with regard to their molecular structure and immunogenicity, and
      some are already available for component-resolved allergy diagnostics. The
      distribution of various mammalian allergens has been extensively studied during
      the past few decades. Animal allergens were found to be ubiquitous in the human
      environment, even in places where no animals reside, with concentrations
      differing considerably between locations and geographical regions. This review
      presents an overview of identified mammalian respiratory allergens classified
      according to protein families, and compiles the results of allergen exposure
      assessment studies conducted in different public and occupational environments.

PMID- 29056699
TI  - Leaner, Healthier, Happier Together--A Family-Centred Approach to Weight Loss
      with the Overweight Dog and Her Caregivers.
AB  - Obesity represents a one of the most significant healthcare issues facing human
      and companion animal populations worldwide. A complex relationship commonly
      exists between owners and their companion animal, particularly around feeding
      behaviour. Obese companion animals commonly live alongside caregivers who are
      also struggling with their own body weight. This case report highlights the
      importance of a family-centred approach to canine obesity as a way to engage with
      the pet's caregivers to help maximize their compliance towards the successful
      implementation of a tailored weight loss programme. Lara, an overweight dog
      weighing 35 kilos with a body condition score (BCS) of 7-7.5/9, was referred for
      a nutritional assessment. A comprehensive, pro-active and multidisciplinary
      protocol, tailored towards a family-centred approach, was established. After a 16
      week programme, Lara reached the target body weight. The caregivers' compliance
      was assessed as being excellent; they also reassessed their individual lifestyle
      and were able to increase awareness towards their own nutritional issues and body
      weight perception, resulting in weight loss in all caregivers. Lara's case report
      represents how a family-centred approach can lead to successful patient weight
      loss and to a modification in the caregivers' way of thinking about nutrition and
      their own lifestyle, with the final goal of living a healthier and longer life
      together.

PMID- 29056700
TI  - How Behavioral Changes Can Indicate Serious Cerebral Pathology: A Case Report of
      Concomitant Olfactory Neuroblastoma and Distemper Virus Encephalitis in a Swiss
      Shepherd Dog.
AB  - Behavioral alterations in dogs are not easy to understand and cure. The situation
      is more difficult when an encephalitis due to Canine Distemper Virus (CDV) and a
      concomitant olfactory neuroblastoma are present. This case report deals with the
      story of a 5-year-old Swiss shepherd dog with behavioral changes, seizures,
      epistaxis and ataxia. Following clinical and laboratory exams, a suspected
      diagnosis of CDV infection was hypothesized, and a therapy based on Omega
      interferon was administered. Every supporting therapy failed and the worsening of
      the clinical conditions led to the euthanasia of the patient. A neoformation in
      the right frontal lobe was found post mortem. Histopathology and
      immunohistochemistry investigation showed a non-suppurative demyelinating
      encephalitis, suggestive of CDV infection, and a desmoplastic epithelioid
      olfactory neuroblastoma. To the best of authors' knowledge, this is the first
      clinical pathological report of a non-suppurative encephalitis due to CDV
      infection and olfactory neuroblastoma in a dog.

PMID- 29056701
TI  - Prevalence of Selected Zoonotic and Vector-Borne Agents in Dogs and Cats on the
      Pine Ridge Reservation.
AB  - The prevalence of intestinal parasites and vector-borne agents of dogs and cats
      in the Pine Ridge Reservation, South Dakota were determined. Fecal samples (84
      dogs, 9 cats) were examined by centrifugal floatation and by immunofluorescence
      assay (FA) for Giardia and Cryptosporidium. PCR was performed on Giardia [beta
      giardin (bg), triose phosphate isomerase (tpi), glutamate dehydrogenase genes
      (gdh)] and Cryptosporidium [heat shock protein-70 gene (hsp)] FA positive
      samples. Cat sera (n = 32) were tested for antibodies against Bartonella spp.,
      Toxoplasma gondii, and FIV, and antigens of FeLV and Dirofilaria immitis. Dog
      sera (n = 82) were tested for antibodies against T. gondii, Borrelia burgdorferi,
      Ehrlichia canis, and Anaplasma phagocytophilum and D. immitis antigen. Blood
      samples (92 dogs, 39 cats) were assessed by PCR for amplification of DNA of
      Bartonella spp., Ehrlichia spp., Anaplasma spp., haemoplasmas, and Babesia spp.
      (dogs only). The most significant results were Giardia spp. (32% by FA), Taenia
      spp. (17.8%) and Cryptosporidium spp. (7.1%). The Giardia isolates typed as the
      dog-specific assemblages C or D and four Cryptosporidium isolates typed as C.
      canis. Antibodies against T. gondii were detected in 15% of the dogs. Antibodies
      against Bartonella spp. and against T. gondii were detected in 37.5% and 6% of
      the cats respectively. FeLV antigen was detected in 10% of the cats.

PMID- 29056702
TI  - Equine Assisted Interventions (EAIs): Methodological Considerations for Stress
      Assessment in Horses.
AB  - Equine assisted interventions (EAIs) are recently facing an increasing
      popularity, and are characterized by a wide diversity of practices. However,
      information on the welfare of animals involved in this kind of activity is often
      lacking. Horses are highly susceptible to work stressors related to physical
      constraints and/or to the need to control emotions while interacting with humans.
      Considerations of the emotional state of horses involved in EAIs have multiple
      valences: for the safety of humans and animals involved, for the quality and
      efficacy of interventions, as well as for ethical reasons. The aim of this
      unsystematic narrative review is to summarize the different approaches used for
      the evaluation of horses' stress responses, investigate their application in the
      context of EAIs, and discuss some methodological considerations for researchers
      and practitioners involved in EAI. The sources of information are mostly based on
      electronic databases (i.e., Medline, Scopus and Google scholar), as well as on
      hand searches of the references of retrieved literature, and discussions with
      experts in the field. At present, a few studies have investigated horses' stress
      responses during EAIs, and further studies are recommended, with the final aim to
      derive a reliable multidimensional method for assessing a horse's reaction during
      therapeutic programs, ultimately helping professionals to better develop
      interventions by taking into consideration the animal's perspective.

PMID- 29056703
TI  - Complete Resolution of a Recurrent Canine Anal Sac Squamous Cell Carcinoma with
      Palliative Radiotherapy and Carboplatin Chemotherapy.
AB  - Anal sac squamous cell carcinoma (SCC) is a rare tumor in dogs. Only eight cases
      have been described in the literature, and previous reports of treatment only
      describe surgery or palliative treatment with non-steroidal anti-inflammatory
      drugs. We report a case of a 12-year-old female neutered Labrador with locally
      advanced anal sac SCC. The dog was treated with four cycles of carboplatin 300
      mg/m2 and four weekly fractions of 8.5 Gy radiation. The dog achieved a complete
      response, and one year later the dog is still alive and well with no evidence of
      tumor recurrence. Radiotherapy in combination with carboplatin chemotherapy was
      effective in the long-term control of this rare disease.

PMID- 29056704
TI  - Infection by Microsporum canis in Paediatric Patients: A Veterinary Perspective.
AB  - Microsporum canis is a dermatophyte fungus of which cats and dogs are recognized
      as the natural hosts. M. canis is also easily transmitted to humans, causing
      lesions to the glabrous skin (tinea corporis) and to the head (tinea capitis).
      The present study describes some cases of infection with M. canis in children
      from a veterinary perspective, highlighting some important features of this
      clinical entity (e.g., the necessity to identify the animal source of infection
      with appropriate diagnostic tests; the fact that infected cats may present with
      no or atypical dermatological signs; and the importance of the environment as a
      fungal reserve).

PMID- 29056706
TI  - The Effects of Music during a Physical Examination Skills Practice: A Pilot
      Study.
AB  - Some veterinary students experience elevated stress, anxiety, and depression
      resulting in disease and psychological changes. Elevated arousal, negative moods,
      and lack of interest can negatively affect performance and learning.
      Psychoacoustic music promotes calming effects using simple and slow piano sounds
      and can positively impact well-being and functioning. This pilot study assessed
      the effects of music on blood pressure, pulse, arousal, and mood during a canine
      physical examination laboratory. In an AB/BA crossover study, 17 students were
      randomly allocated to practice physical examination skills while listening to
      Through a Dog's Ear, Volume 1. Psychological and physiologic data were collected.
      Nonparametric methods were used to test for significant differences in
      psychological and physiologic data and a linear mixed models approach was used to
      test for physiological differences. There were no significant baseline
      differences between the music and no music groups for DASS-21 depression,
      anxiety, or stress scores; however, there were significant time differences
      between pretest and posttest on arousal and mood as measured by the Profile of
      Mood Sates (POMS) Depression, Fatigue-Inertia, and Tension Anxiety subscales.
      Linear mixed models revealed no significant treatment effect on the pulse and
      diastolic blood pressure; however, there was a significant systolic blood
      pressure treatment effect. Future indications include repeating the study with a
      larger sample to examine longitudinal psychological and physiological benefits.

PMID- 29056705
TI  - Review of Diagnostic and Therapeutic Approach to Canine Myxomatous Mitral Valve
      Disease.
AB  - The most common heart disease that affects dogs is myxomatous mitral valve
      disease. In this article, we review the current diagnostic and therapeutic
      approaches to this disease, and we also present some of the latest technological
      advancements in this field.

PMID- 29056707
TI  - Outcome of an Experimental Study in Growing Turkeys Suspected of Having a Diet
      Related, Uncommon and Uncoordinated Gait.
AB  - On the occasion of a clinical case on a turkey farm and based on the suspicion
      that the diet composition could be the cause, an eight-week diagnostic trial was
      performed with turkey poults (n = 54) divided into two groups (control and
      experimental). The levels of vitamin A in the starter and grower diets of the
      control group were 7168 and 5213 IU/kg diet, but <1000 IU/kg in the experimental
      ones. Vitamin A and uric acid contents were measured in the serum, while liver
      samples were taken to determine the vitamin A content. Parts of the central
      nervous system and some internal organs were examined histologically. In the
      sixth week, ruffled feathers and uncoordinated gait were the earliest signs seen
      in the experimental group. The vitamin A content in the liver samples
      significantly decreased in the experimental group (0.09 mg/kg vs. 29.5 mg/kg).
      The serum level of uric acid in the experimental group was significantly higher
      (12.8 mg/dL vs. 3.38 mg/dL). Birds in the experimental group showed squamous
      metaplasia in the oesophagus. No histopathological alterations were seen in the
      central nervous system. The elevated uric acid level in the serum is worth
      mentioning.

PMID- 29056708
TI  - A Preliminary Assessment of HTST Processing on Donkey Milk.
AB  - Due to increasing attention from consumers on non-bovine milk types, and to the
      increase in the number of small dairy donkey farms in Italy, farmers require more
      advanced and reliable processing devices, in order to guarantee a safe product of
      high quality. To this aim, a new small-scale High-Temperature Short-Time (HTST)
      pasteurizer (72  degrees C for 15 s), prototyped by the authors, was tested on
      donkey milk. The efficacy of the HTST device was tested on raw donkey milk
      microflora by enumeration of total aerobic bacteria, Enterobacteriaceae and
      Bacillus cereus. The biochemical quality was assessed by determining the protein
      profile by monodimensional electrophoresis and by measuring lysozyme activity.
      The HTST apparatus was able to reduce the total bacteria count, and to completely
      eradicate Enterobacteriaceae. Bacillus cereus, when present, was decreased with
      low efficiency. Changes in the protein profile were observed in milk pasteurized
      in accordance with both processes, although HTST seemed to limit casein
      degradation. Lysozyme activity was not substantially affected in comparison to
      raw donkey milk. In conclusion, a tailored small-volume HTST device could be
      safely applied to pasteurize donkey milk in on-farm pasteurization processes on
      small dairy donkey farms.

PMID- 29056709
TI  - Detection of Leptospira spp. in Water Turtle (Trachemys scripta) Living in Ponds
      of Urban Parks.
AB  - Urban parks are green areas of cities where families and children spend hours
      outside. Turtles often inhabit urban parks. However, even if the animals seem
      harmless, they may serve as both reservoirs or accidental hosts for different
      serotypes of Leptospira spp. Leptospira spp. is a waterborne zoonotic bacterium
      relevant for public health. Reptiles and amphibians may play a role in the
      epidemiology, transmission, and persistence of Leptospira spp. In the present
      study, we observed the presence of anti-leptospiral agglutinins in a group of
      freshwater turtles (Trachemys scripta) captured in three urban ponds of the
      metropolitan city of Turin, Italy.

PMID- 29056710
TI  - Small Pilot Survey on Parents' Perception of the Relationship between Children
      and Pets.
AB  - Since companion animals are taking on more important roles in family life, the
      aim of this study was to evaluate the perception of parents about the
      relationship between their children and pets. A number of parents were asked to
      fill in a questionnaire; the principal topics were: pet ownership, pet care,
      relationship between pets and children, and sources of information about pet
      management. Eighty-two parents completed the survey; 71.4% of them already had
      pets before having children; pet care and health has emerged to be rather
      important, since 96.4% of the pets are taken to the veterinarian at least once a
      year; moreover, the great majority of the parents (97.2%) were not worried about
      the possible risks, linked to pets, pertaining to their child's health. The
      present survey confirms that pets are mostly considered as members of the family,
      and not only as a benefit for the children. Moreover, the relationship between
      children and pets is basically seen as a positive experience for children.

PMID- 29056711
TI  - Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression.
AB  - Breast cancer represents the second most frequent neoplasm in humans and sexually
      intact female dogs after lung and skin cancers, respectively. Many similar
      features in human and dog cancers including, spontaneous development, clinical
      presentation, tumor heterogeneity, disease progression and response to
      conventional therapies have supported development of this comparative model as an
      alternative to mice. The highly conserved similarities between canine and human
      genomes are also key to this comparative analysis, especially when compared to
      the murine genome. Studies with canine mammary tumor (CMT) models have shown a
      strong genetic correlation with their human counterparts, particularly in terms
      of altered expression profiles of cell cycle regulatory genes, tumor suppressor
      and oncogenes and also a large group of non-coding RNAs or microRNAs (miRNAs).
      Because CMTs are considered predictive intermediate models for human breast
      cancer, similarities in genetic alterations and cancer predisposition between
      humans and dogs have raised further interest. Many cancer-associated genetic
      defects critical to mammary tumor development and oncogenic determinants of
      metastasis have been reported and appear to be similar in both species.
      Comparative analysis of deregulated gene sets or cancer signaling pathways has
      shown that a significant proportion of orthologous genes are comparably up- or
      down-regulated in both human and dog breast tumors. Particularly, a group of cell
      cycle regulators called cyclin-dependent kinase inhibitors (CKIs) acting as
      potent tumor suppressors are frequently defective in CMTs. Interestingly,
      comparative analysis of coding sequences has also shown that these genes are
      highly conserved in mammals in terms of their evolutionary divergence from a
      common ancestor. Moreover, co-deletion and/or homozygous loss of the
      INK4A/ARF/INK4B (CDKN2A/B) locus, encoding three members of the CKI tumor
      suppressor gene families (p16/INK4A, p14ARF and p15/INK4B), in many human and dog
      cancers including mammary carcinomas, suggested their important conserved genetic
      order and localization in orthologous chromosomal regions. miRNAs, as powerful
      post-transcriptional regulators of most of the cancer-associated genes, have not
      been well evaluated to date in animal cancer models. Comprehensive expression
      profiles of miRNAs in CMTs have revealed their altered regulation showing a
      strong correlation with those found in human breast cancers. These genetic
      correlations between human and dog mammary cancers will greatly advance our
      understanding of regulatory mechanisms involving many critical cancer-associated
      genes that promote neoplasia and contribute to the promising development of
      future therapeutics.

PMID- 29056712
TI  - Canine Histiocytic Malignancies-Challenges and Opportunities.
AB  - Canine histiocytic malignancies (HM) are aggressive tumors that occur with
      particularly high frequency in certain breeds including Bernese mountain dogs and
      flat-coated retrievers. Robust diagnosis of HM commonly utilizes
      immunohistochemical stains that are broadly ineffective on formalin-fixed
      tissues; thus the diagnosis is often one of exclusion. Clinical outcomes are
      generally poor, with frequent metastasis and therapeutic failure lowering overall
      survival at time of diagnosis to an average of less than two months in the
      majority of published work. The limited understanding of the molecular mechanisms
      underlying HM has hindered the development of more effective diagnostic
      modalities and the identification of therapeutic targets. A potential avenue
      exists for advancing clinical management of canine cancers through extrapolation
      from a close counterpart in human medicine. Historically, HM have been compared
      to the rare and understudied subset of human cancers involving the dendritic
      lineage, such as dendritic cell sarcoma or Langerhans cell sarcoma. Recent data
      have now thrown into question the cellular origin of HM, suggesting that the
      disease may originate from the macrophage lineage. This review summarizes
      existing knowledge of HM from the clinical, histologic and molecular
      perspectives, and highlights avenues for future research that may aid the
      development of novel diagnostic and therapeutic approaches. In turn, a more
      advanced appreciation of the mechanisms underlying HM should clarify their
      cellular origin and identify appropriate opportunities for synergistic
      extrapolation between related canine and human cancers.

PMID- 29056713
TI  - Understanding the Osteosarcoma Pathobiology: A Comparative Oncology Approach.
AB  - Osteosarcoma is an aggressive primary bone tumor in humans and is among the most
      common cancer afflicting dogs. Despite surgical advancements and intensification
      of chemo- and targeted therapies, the survival outcome for osteosarcoma patients
      is, as of yet, suboptimal. The presence of metastatic disease at diagnosis or its
      recurrence after initial therapy is a major factor for the poor outcomes. It is
      thought that most human and canine patients have at least microscopic metastatic
      lesions at diagnosis. Osteosarcoma in dogs occurs naturally with greater
      frequency and shares many biological and clinical similarities with osteosarcoma
      in humans. From a genetic perspective, osteosarcoma in both humans and dogs is
      characterized by complex karyotypes with highly variable structural and numerical
      chromosomal aberrations. Similar molecular abnormalities have been observed in
      human and canine osteosarcoma. For instance, loss of TP53 and RB regulated
      pathways are common. While there are several oncogenes that are commonly
      amplified in both humans and dogs, such as MYC and RAS, no commonly activated
      proto-oncogene has been identified that could form the basis for targeted
      therapies. It remains possible that recurrent aberrant gene expression changes
      due to gene amplification or epigenetic alterations could be uncovered and these
      could be used for developing new, targeted therapies. However, the remarkably
      high genomic complexity of osteosarcoma has precluded their definitive
      identification. Several advantageous murine models of osteosarcoma have been
      generated. These include spontaneous and genetically engineered mouse models,
      including a model based on forward genetics and transposon mutagenesis allowing
      new genes and genetic pathways to be implicated in osteosarcoma development. The
      proposition of this review is that careful comparative genomic studies between
      human, canine and mouse models of osteosarcoma may help identify commonly
      affected and targetable pathways for alternative therapies for osteosarcoma
      patients. Translational research may be found through a path that begins in mouse
      models, and then moves through canine patients, and then human patients.

PMID- 29056714
TI  - Therapeutic Innovations: Tyrosine Kinase Inhibitors in Cancer.
AB  - Conventional cytotoxic chemotherapy involving DNA-interacting agents and
      indiscriminate cell death is no longer the future of cancer management. While
      chemotherapy is not likely to completely disappear from the armamentarium; the
      use of targeted therapies in combination with conventional treatment is becoming
      the standard of care in human medicine. Tyrosine kinases are pivotal points of
      functional cellular pathways and have been implicated in malignancy,
      inflammatory, and immune-mediated diseases. Pharmaceutical interventions
      targeting aberrant tyrosine kinase signaling has exploded and is the second most
      important area of drug development. The "Valley of Death" between drug discovery
      and approval threatens to blunt the enormous strides in cancer management seen
      thus far. Kinase inhibitors, as targeted small molecules, hold promise in the
      treatment and diagnosis of cancer. However, there are still many unanswered
      questions regarding the use of kinase inhibitors in the interpretation and
      management of cancer. Comparative oncology has the potential to address
      restrictions and limitations in the advancement in kinase inhibitor therapy.

PMID- 29056716
TI  - An Alternative Vaccination Approach for The Prevention of Highly Pathogenic Avian
      Influenza Subtype H5N1 in The Red River Delta, Vietnam -A Geospatial-Based Cost
      Effectiveness Analysis.
AB  - This study addresses the tradeoff between Vietnam's national poultry vaccination
      program, which implemented an annual two-round HPAI H5N1 vaccination program for
      the entire geographical area of the Red River Delta during the period from 2005
      2010, and an alternative vaccination program which would involve vaccination for
      every production cycle at the recommended poultry age in high risk areas within
      the Delta. The ex ante analysis framework was applied to identify the location of
      areas with high probability of HPAI H5N1 occurrence for the alternative
      vaccination program by using boosted regression trees (BRT) models, followed by
      weighted overlay operations. Cost-effectiveness of the vaccination programs was
      then estimated to measure the tradeoff between the past national poultry
      vaccination program and the alternative vaccination program. Ex ante analysis
      showed that the focus areas for the alternative vaccination program included 1137
      communes, corresponding to 50.6% of total communes in the Delta, and located
      primarily in the coastal areas to the east and south of Hanoi. The cost
      effectiveness analysis suggested that the alternative vaccination program would
      have been more successful in reducing the rate of disease occurrence and the
      total cost of vaccinations, as compared to the national poultry vaccination
      program.

PMID- 29056718
TI  - Sentinel Animals in a One Health Approach to Harmful Cyanobacterial and Algal
      Blooms.
AB  - People, domestic animals, and wildlife are all exposed to numerous environmental
      threats, including harmful algal blooms (HABs). However, because animals exhibit
      wide variations in diet, land use and biology, they are often more frequently or
      heavily exposed to HAB toxins than are people occupying the same habitat, making
      them sentinels for human exposures. Historically, we have taken advantage of
      unique physiological characteristics of animals, such as the sensitivity of
      canaries to carbon monoxide, to more quickly recognize threats and help protect
      human health. As HAB events become more severe and widespread worldwide, exposure
      and health outcome data for animals can be extremely helpful to predict, prevent,
      and evaluate human exposures and health outcomes. Applying a One Health approach
      to investigation of HABs means that lessons learned from animal sentinels can be
      applied to protect people, animals and our shared environment.

PMID- 29056717
TI  - Comparative Aspects of Canine Melanoma.
AB  - Melanomas are malignant neoplasms originating from melanocytes. They occur in
      most animal species, but the dog is considered the best animal model for the
      disease. Melanomas in dogs are most frequently found in the buccal cavity, but
      the skin, eyes, and digits are other common locations for these neoplasms. The
      aim of this review is to report etiological, epidemiological, pathological, and
      molecular aspects of melanomas in dogs. Furthermore, the particular biological
      behaviors of these tumors in the different body locations are shown. Insights
      into the therapeutic approaches are described. Surgery, chemotherapy,
      radiotherapy, immunotherapy, and the outcomes after these treatments are
      presented. New therapeutic perspectives are also depicted. All efforts are geared
      toward better characterization and control of malignant melanomas in dogs, for
      the benefit of these companion animals, and also in an attempt to benefit the
      treatment of human melanomas.

PMID- 29056719
TI  - Establishment and Characterization of New Canine and Feline Osteosarcoma Primary
      Cell Lines.
AB  - Osteosarcomas are the most abundant form of bone malignancies in multiple
      species. Canine osteosarcomas are considered a valuable model for human
      osteosarcomas because of their similar features. Feline osteosarcomas, on the
      other hand, are rarely studied but have interesting characteristics, such as a
      better survival prognosis than dogs or humans, and less likelihood of metastasis.
      To enable experimental approaches to study these differences we have established
      five new canine osteosarcoma cell lines out of three tumors, COS_1186h,
      COS_1186w, COS_1189, and COS_1220, one osteosarcoma-derived lung metastasis,
      COS_1033, and two new feline osteosarcoma cell lines, FOS_1077 and FOS_1140.
      Their osteogenic and neoplastic origin, as well as their potential to produce
      calcified structures, was determined by the markers osteocalcin, osteonectin,
      tissue unspecific alkaline phosphatase, p53, cytokeratin, vimentin, and alizarin
      red. The newly developed cell lines retained most of their markers in vitro but
      only spontaneously formed spheroids produced by COS_1189 showed calcification in
      vitro.

PMID- 29056720
TI  - Sequence Instability in the Proviral Long Terminal Repeat and gag Regions from
      Peripheral Blood and Tissue-Derived Leukocytes of FIV-Infected Cats during the
      Late Asymptomatic Phase.
AB  - Feline immunodeficiency virus (FIV) infection results in viral persistence, a
      prolonged asymptomatic phase, and progressive immunopathology. During the
      asymptomatic phase, a cohort of experimentally FIV-infected cats exhibits
      features of viral latency in blood suggestive of inactive viral replication. We
      sought to investigate viral replication activity and genomic stability of the FIV
      proviral long terminal repeat (LTR) and the 5' aspect of gag over time. FIV
      infected cats during the asymptomatic phase demonstrated undetectable plasma FIV
      gag RNA transcripts and intermittent to undetectable blood-derived cell
      associated FIV gag RNA. The LTR sequence demonstrated instability in blood
      derived cells over time, in spite of low to undetectable viral replication.
      Sequence variation in the LTR was identified in CD4+ and CD21+ leukocytes from
      blood and surgically removed lymph nodes. Three single nucleotide polymorphisms
      (SNPs) in the LTR were commonly identified. Promoter functionality of a common
      LTR SNP and rare U3 mutation were examined by reporter gene assays and
      demonstrated either no change or increased basal FIV promoter function,
      respectively. In conclusion, this cohort of asymptomatic FIV-infected cats
      demonstrated instability of the LTR and 5' gag sequences during the study period,
      in spite of undetectable plasma and rare to undetectable viral gag RNA, which
      suggests that blood may not accurately represent viral activity in asymptomatic
      FIV-infected cats.

PMID- 29056722
TI  - Gliomatosis Cerebri in the Brain of a Cat.
AB  - An eight-year-old, neutered, female, long-haired cat was presented with a three
      week history of progressive lethargy, unlocalized pain in the cervical and lumbar
      spine, and unwillingness to move. An MRI (magnetic resonance imaging) of the
      brain revealed poorly circumscribed regions of non-contrast-enhancing
      heterogeneous T2 hyperintensity within the ventral forebrain and midbrain. A mass
      effect and evidence of increased intracranial pressure, including transtentorial
      herniation of the midbrain and herniation of the cerebellar vermis through the
      foramen magnum, were also observed. Due to progressive clinical decline and MRI
      results, the cat was humanely euthanized. Gross examination of the brain
      confirmed caudal transtentorial and foramen magnum herniation. The ventral aspect
      of the forebrain, midbrain, and brainstem were soft and had loss of detail, but
      lacked a grossly discernible mass. Histopathological examination found a poorly
      delineated neoplastic mass composed of hyperchromatic cells with indistinct
      cytoplasm, ovoid to elongate or curved nuclei, and indistinct nucleoli. The cells
      lacked immunoreactivity for Olig2, GFAP, Iba1, CD3, and Pax5. Based on the
      cellular morphology, immunolabeling characteristics, and anatomical location, a
      diagnosis of gliomatosis cerebri was made. Although uncommon, gliomatosis cerebri
      should be considered as a differential diagnosis in cats with central nervous
      system disease.

PMID- 29056721
TI  - Travelling between Two Worlds: Complement as a Gatekeeper for an Expanded Host
      Range of Lyme Disease Spirochetes.
AB  - Evading innate immunity is a prerequisite for pathogenic microorganisms in order
      to survive in their respective hosts. Concerning Lyme disease spirochetes
      belonging to the Borrelia (B.) burgdorferi sensu lato group, a broad range of
      diverse vertebrates serve as reservoir or even as incidental hosts, including
      humans. The capability to infect multiple hosts implies that spirochetes have
      developed sophisticated means to counter the destructive effects of complement of
      humans and various animals. While the means by which spirochetes overcome the
      hosts immune defense are far from being completely understood, there is a growing
      body of evidence suggesting that binding of the key regulator of the alternative
      pathway, Factor H, plays a pivotal role for immune evasion and that Factor H is
      an important determinant of host specificity. This review covers (i) the
      contribution of complement in host-specificity and transmissibility of Lyme
      disease spirochetes; (ii) the involvement of borrelial-derived determinants to
      host specificity; (iii) the interplay of human and animal Factor H with
      complement-acquiring surface proteins of diverse borrelial species; and (iv) the
      potential role of additional animal complement proteins in the immune evasion of
      spirochetes.

PMID- 29056723
TI  - Detection of Methicillin-Resistant Staphylococci Isolated from Food Producing
      Animals: A Public Health Implication.
AB  - The emergence of antibiotic-resistant bacteria in food animals is a potential
      public health concern. Staphylococci are a significant opportunistic pathogen
      both in humans and dairy cattle. In the present study, the genotypic
      characterization of methicillin-resistant staphylococcal strains recovered from
      dairy cattle in a rural community (Okada, Edo State, Nigeria) was investigated. A
      total of 283 samples from cattle (137 milk samples and 146 nasal swabs) were
      assessed between February and April 2015. Antimicrobial susceptibility was
      performed by Kirby-Bauer disc diffusion method. Polymerase chain reaction (PCR)
      assay was employed for the detection of 16S rRNA, mecA and Panton-Valentine
      Leucocidinis (PVL) genes. The staphylococcal strains were identified through
      partial 16S ribosomal ribonucleic acids (rRNA) nucleotide sequencing, and Basic
      Local Alignment Search Tool (BLAST) analysis of the gene sequence showed that the
      staphylococcal strains have 96%-100% similarity to Staphylococcus aureus (30), S.
      epidermidis (17), S. haemolyticus (15), S. saprophyticus (13), S. chromogenes
      (8), S. simulans (7), S. pseudintermedius (6) and S. xylosus (4). Resistance of
      100% was observed in all Staphylococcus spp. against MET, PEN, CLN, CHL and SXT.
      Multi-drug resistant (MDR) bacteria from nasal cavities and raw milk reveals 13
      isolates were MDR against METR, PENR, AMXR, CLNR, CHLR, SXTR CLXR, KANR, ERYR,
      and VANR. Of all isolates, 100% harboured the mecA gene, while 30% of the
      isolates possess the PVL gene. All S. aureus harboured the PVL gene while other
      Staphylococcus spp. were negative for the PVL gene. The presence of methicillin
      resistant Staphylococcus spp. isolates in dairy cattle is a potential public
      health risk and thus findings in this study can be used as a baseline for further
      surveillance.

PMID- 29056724
TI  - Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms
      to Establish Infection.
AB  - Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and
      animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate
      intracellular bacterium evolved to use common strategies to establish infection
      in both vertebrate hosts and tick vectors. Herein, we discuss the different
      strategies used by the pathogen to modulate cell apoptosis and establish
      infection in host cells. In vertebrate neutrophils and human promyelocytic cells
      HL-60, both pro-apoptotic and anti-apoptotic factors have been reported. Tissue
      specific differences in tick response to infection and differential regulation of
      apoptosis pathways have been observed in adult female midguts and salivary glands
      in response to infection with A. phagocytophilum. In tick midguts, pathogen
      inhibits apoptosis through the Janus kinase/signal transducers and activators of
      transcription (JAK/STAT) pathway, while in salivary glands, the intrinsic
      apoptosis pathways is inhibited but tick cells respond with the activation of the
      extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection
      down-regulates mitochondrial porin and manipulates protein processing in the
      endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and
      facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis
      appears to be regulated by lower caspase levels. These results suggest that A.
      phagocytophilum uses different mechanisms to inhibit apoptosis for infection of
      both vertebrate and invertebrate hosts.

PMID- 29056726
TI  - p16, pRb, and p53 in Feline Oral Squamous Cell Carcinoma.
AB  - Feline oral squamous cell carcinoma (FOSCC) is a highly aggressive head and neck
      cancer in cats, but the molecular pathogenesis of this cancer is still uncertain.
      In this study, p16, p53, and pRb proteins were detected and quantified by
      immunohistochemistry in forty-three FOSCC primary tumors and three FOSCC
      xenografts. p16 mRNA levels were also measured in three FOSCC cell lines (SCCF1,
      F2, and F3), which were consistent with their p16 immunoreactivity. Feline SCCF1
      cells had very high levels of p16 protein and mRNA (55-fold greater) compared to
      SCCF2 and F3. A partial feline p16 cDNA sequence was amplified and sequenced. The
      average age of cats with FOSCC with high p16 immunoreactivity was significantly
      lower than the average age in the low p16 group. Eighteen of 43 (42%) FOSCCs had
      low p16 intensity, while 6/43 (14%) had high p16 immunoreactivity. Feline
      papillomavirus L1 (major capsid) DNA was not detected in the SCC cell lines or
      the FOSCCs with high p16 immunostaining. Five of 6 (83%) of the high p16 FOSCC
      had low p53, but only 1/6 (17%) had low pRb immunoreactivity. In summary, the
      staining pattern of p16, p53, and pRb in FOSCC was different from human head and
      neck squamous cell carcinoma and feline cutaneous squamous cell carcinoma. The
      majority of FOSCCs have low p16 immunostaining intensity, therefore, inactivation
      of CDKN2A is suspected to play a role in the pathogenesis of FOSCC. A subset of
      FOSCCs had increased p16 protein, which supports an alternate pathogenesis of
      cancer in these cats.

PMID- 29056725
TI  - Cat Mammary Tumors: Genetic Models for the Human Counterpart.
AB  - The records are not clear, but Man has been sheltering the cat inside his home
      for over 12,000 years. The close proximity of this companion animal, however,
      goes beyond sharing the same roof; it extends to the great similarity found at
      the cellular and molecular levels. Researchers have found a striking resemblance
      between subtypes of feline mammary tumors and their human counterparts that goes
      from the genes to the pathways involved in cancer initiation and progression.
      Spontaneous cat mammary pre-invasive intraepithelial lesions (hyperplasias and
      neoplasias) and malignant lesions seem to share a wide repertoire of molecular
      features with their human counterparts. In the present review, we tried to
      compile all the genetics aspects published (i.e., chromosomal alterations,
      critical cancer genes and their expression) regarding cat mammary tumors, which
      support the cat as a valuable alternative in vitro cell and animal model (i.e.,
      cat mammary cell lines and the spontaneous tumors, respectively), but also to
      present a critical point of view of some of the issues that really need to be
      investigated in future research.

PMID- 29056729
TI  - Genomic Tools and Animal Health.
AB  - Animals have been selected to improve their productivity in order to increase the
      profitability to the producer. In this scenario, not much attention was given to
      health traits. As a consequence of that, selection was made for animals with
      higher production and a shortened productive life. In addition to that, the
      intense production system used in livestock has forced animals to be exposed to
      higher pathogen loads, therefore predisposing them to infections. Infectious
      diseases are known to be caused by micro-organisms that are able to infect and
      colonize the host, affecting their physiological functions and causing problems
      in their production and on animal welfare. Even with the best management
      practices, diseases are still the most important cause of economic losses in the
      animal industry. In this review article we have addressed the new tools that
      could be used to select animals to better cope with diseases and pathogens.

PMID- 29056727
TI  - Pathogen and Host Response Dynamics in a Mouse Model of Borrelia hermsii
      Relapsing Fever.
AB  - Most Borrelia species that cause tick-borne relapsing fever utilize rodents as
      their natural reservoirs, and for decades laboratory-bred rodents have served as
      informative experimental models for the disease. However, while there has much
      progress in understanding the pathogenetic mechanisms, including antigenic
      variation, of the pathogen, the host side of the equation has been neglected.
      Using different approaches, we studied, in immunocompetent inbred mice, the
      dynamics of infection with and host responses to North American relapsing fever
      agent B. hermsii. The spirochete's generation time in blood of infected mice was
      between 4-5 h and, after a delay, was matched in rate by the increase of specific
      agglutinating antibodies in response to the infection. After initiating serotype
      cells were cleared by antibodies, the surviving spirochetes were a different
      serotype and, as a population, grew more slowly. The retardation was attributable
      to the host response and not an inherently slower growth rate. The innate
      responses at infection peak and immediate aftermath were characterized by
      elevations of both pro-inflammatory and anti-inflammatory cytokines and
      chemokines. Immunodeficient mice had higher spirochete burdens and severe anemia,
      which was accounted for by aggregation of erythrocytes by spirochetes and their
      partially reversible sequestration in greatly enlarged spleens and elsewhere.

PMID- 29056730
TI  - Forced-Air Warming Provides Better Control of Body Temperature in Porcine
      Surgical Patients.
AB  - Background: Maintaining normothermia during porcine surgery is critical in
      ensuring subject welfare and recovery, reducing the risk of immune system
      compromise and surgical-site infection that can result from hypothermia. In
      humans, various methods of patient heating have been demonstrated to be useful,
      but less evaluation has been performed in techniques to prevent hypothermia
      perioperatively in pigs. Methods: We compared body temperature regulation during
      surgery before and after modification of the ambient temperature of the operating
      laboratories. Three different methods of heating were then compared; a standard
      circulating water mattress, a resistive fabric blanket, and a forced hot air
      system. The primary measure was percentage of temperature readings outside a
      specification range of 36.7-40.0  degrees C. Results: Tighter control of the
      ambient temperature while using a circulating water mattress reduced the
      occurrence of out-of-specification body temperature readings from 20.8% to 5.0%,
      with most of these the result of hypothermia. Use of a resistive fabric blanket
      further reduced out-of-specification readings to 1.5%, with a slight increase in
      the occurrence of hyperthermia. Use of a forced air system reduced out-of
      specification readings to less 0.1%. Conclusions: Maintenance of normothermia
      perioperatively in pig can be improved by tightly controlling ambient
      temperatures. Use of a resistive blanket or a forced air system can lead to
      better control than a circulating water mattress, with the forced air system
      providing a faster response to temperature variations and less chance of
      hyperthermia.

PMID- 29056728
TI  - Ehrlichioses: An Important One Health Opportunity.
AB  - Ehrlichioses are caused by obligately intracellular bacteria that are maintained
      subclinically in a persistently infected vertebrate host and a tick vector. The
      most severe life-threatening illnesses, such as human monocytotropic ehrlichiosis
      and heartwater, occur in incidental hosts. Ehrlichia have a developmental cycle
      involving an infectious, nonreplicating, dense core cell and a noninfectious,
      replicating reticulate cell. Ehrlichiae secrete proteins that bind to host
      cytoplasmic proteins and nuclear chromatin, manipulating the host cell
      environment to their advantage. Severe disease in immunocompetent hosts is
      mediated in large part by immunologic and inflammatory mechanisms, including
      overproduction of tumor necrosis factor alpha (TNF-alpha), which is produced by
      CD8 T lymphocytes, and interleukin-10 (IL-10). Immune components that contribute
      to control of ehrlichial infection include CD4 and CD8 T cells, natural killer
      (NK) cells, interferon-gamma (IFN-gamma), IL-12, and antibodies. Some immune
      components, such as TNF-alpha, perforin, and CD8 T cells, play both pathogenic
      and protective roles. In contrast with the immunocompetent host, which may die
      with few detectable organisms owing to the overly strong immune response,
      immunodeficient hosts die with overwhelming infection and large quantities of
      organisms in the tissues. Vaccine development is challenging because of antigenic
      diversity of E. ruminantium, the necessity of avoiding an immunopathologic
      response, and incomplete knowledge of the protective antigens.

PMID- 29056731
TI  - Comparative Pathogenesis of Cancers in Animals and Humans.

PMID- 29056732
TI  - An Evaluation of Quantitative PCR Assays (TaqMan(r) and SYBR Green) for the
      Detection of Babesia bigemina and Babesia bovis, and a Novel Fluorescent-ITS1-PCR
      Capillary Electrophoresis Method for Genotyping B. bovis Isolates.
AB  - Babesia spp. are tick-transmitted haemoparasites causing tick fever in cattle. In
      Australia, economic losses to the cattle industry from tick fever are estimated
      at AUD$26 Million per annum. If animals recover from these infections, they
      become immune carriers. Here we describe a novel multiplex TaqMan qPCR targeting
      cytochrome b genes for the identification of Babesia spp. The assay shows high
      sensitivity, specificity and reproducibility, and allows quantification of
      parasite DNA from Babesia bovis and B. bigemina compared to standard PCR assays.
      A previously published cytochrome b SYBR Green qPCR was also tested in this
      study, showing slightly higher sensitivity than the Taqman qPCRs but requires
      melting curve analysis post-PCR to confirm specificity. The SYBR Green assays
      were further evaluated using both diagnostic submissions and vaccinated cattle
      (at 7, 9, 11 and 14 days post-inoculation) showed that B. bigemina can be
      detected more frequently than B. bovis. Due to fewer circulating parasites, B.
      bovis detection in carrier animals requires higher DNA input. Preliminary data
      for a novel fluorescent PCR genotyping based on the Internal Transcribed Spacer 1
      region to detect vaccine and field alleles of B. bovis are described. This assay
      is capable of detecting vaccine and novel field isolate alleles in a single
      sample.

PMID- 29056733
TI  - Anaplasma phagocytophilum-Occupied Vacuole Interactions with the Host Cell
      Cytoskeleton.
AB  - Anaplasma phagocytophilum is an obligate intracellular bacterial pathogen of
      humans and animals. The A. phagocytophium-occupied vacuole (ApV) is a critical
      host-pathogen interface. Here, we report that the intermediate filaments, keratin
      and vimentin, assemble on the ApV early and remain associated with the ApV
      throughout infection. Microtubules localize to the ApV to a lesser extent.
      Vimentin, keratin-8, and keratin-18 but not tubulin expression is upregulated in
      A. phagocytophilum infected cells. SUMO-2/3 but not SUMO-1 colocalizes with
      vimentin filaments that surround ApVs. PolySUMOylation of vimentin by SUMO-2/3
      but not SUMO-1 decreases vimentin solubility. Consistent with this, more vimentin
      exists in an insoluble state in A. phagocytophilum infected cells than in
      uninfected cells. Knocking down the SUMO-conjugating enzyme, Ubc9, abrogates
      vimentin assembly at the ApV but has no effect on the bacterial load. Bacterial
      protein synthesis is dispensable for maintaining vimentin and SUMO-2/3 at the
      ApV. Withaferin A, which inhibits soluble vimentin, reduces vimentin recruitment
      to the ApV, optimal ApV formation, and the bacterial load when administered prior
      to infection but is ineffective once vimentin has assembled on the ApV. Thus, A.
      phagocytophilum modulates cytoskeletal component expression and co-opts
      polySUMOylated vimentin to aid construction of its vacuolar niche and promote
      optimal survival.

PMID- 29056734
TI  - Parallelisms and Contrasts in the Diverse Ecologies of the Anaplasma
      phagocytophilum and Borrelia burgdorferi Complexes of Bacteria in the Far Western
      United States.
AB  - Anaplasma phagocytophilum and Borrelia burgdorferi are two tick-borne bacteria
      that cause disease in people and animals. For each of these bacteria, there is a
      complex of closely related genospecies and/or strains that are genetically
      distinct and have been shown through both observational and experimental studies
      to have different host tropisms. In this review we compare the known ecologies of
      these two bacterial complexes in the far western USA and find remarkable
      similarities, which will help us understand evolutionary histories and
      coadaptation among vertebrate host, tick vector, and bacteria. For both
      complexes, sensu stricto genospecies (those that infect humans) share a similar
      geographic range, are vectored mainly by ticks in the Ixodes ricinus-complex,
      utilize mainly white-footed mice (Peromyscus leucopus) as a reservoir in the
      eastern USA and tree squirrels in the far west, and tend to be generalists,
      infecting a wider variety of vertebrate host species. Other sensu lato
      genospecies within each complex are generally more specialized, occurring often
      in local enzootic cycles within a narrow range of vertebrate hosts and
      specialized vector species. We suggest that these similar ecologies may have
      arisen through utilization of a generalist tick species as a vector, resulting in
      a potentially more virulent generalist pathogen that spills over into humans, vs.
      utilization of a specialized tick vector on a particular vertebrate host species,
      promoting microbe specialization. Such tight host-vector-pathogen coupling could
      also facilitate high enzootic prevalence and the evolution of host immune
      tolerance and bacterial avirulence.

PMID- 29056737
TI  - Characterization of Haptoglobin Isotype in Milk of Mastitis-Affected Cows.
AB  - Haptoglobin is a major acute phase protein in bovines and reportedly increases in
      serum and milk whey during mastitis, highlighting its potential as a diagnostic
      biomarker. Since haptoglobin is known to undergo tissue specific glycosylation
      resulting in different isoforms, this study was undertaken to characterize the
      isoforms of haptoglobin. Milk whey fraction and serum obtained from animals with
      or without clinical mastitis in Puducherry, India, were subjected to SDS-PAGE
      followed by western blot and immuno-detection of haptoglobin protein. All
      subunits (beta, alpha1 and alpha2) of haptoglobin protein were detected in serum
      sample obtained from clinical cases. However, only the beta-subunit was detected
      in milk whey fraction obtained from the respective animals. Similar results were
      observed with milk whey fractions from subclinical cases indicating difference in
      isoform of haptoglobin detected in milk whey from serum. This was further
      supported by RT-PCR (Reverse Transcription Polymerase Chain Reaction) analysis of
      haptoglobin gene (Hp) confirming the tissue specific origin of haptoglobin.

PMID- 29056736
TI  - Microscopic Visualisation of Zoonotic Arbovirus Replication in Tick Cell and
      Organ Cultures Using Semliki Forest Virus Reporter Systems.
AB  - Ticks are vectors and reservoirs of many arboviruses pathogenic for humans or
      domestic animals; in addition, during bloodfeeding they can acquire and harbour
      pathogenic arboviruses normally transmitted by other arthropods such as
      mosquitoes. Tick cell and organ cultures provide convenient tools for propagation
      and study of arboviruses, both tick-borne and insect-borne, enabling elucidation
      of virus-tick cell interaction and yielding insight into the mechanisms behind
      vector competence and reservoir potential for different arbovirus species. The
      mosquito-borne zoonotic alphavirus Semliki Forest virus (SFV), which replicates
      well in tick cells, has been isolated from Rhipicephalus, Hyalomma, and Amblyomma
      spp. ticks removed from mammalian hosts in East Africa; however nothing is known
      about any possible role of ticks in SFV epidemiology. Here we present a light and
      electron microscopic study of SFV infecting cell lines and organ cultures derived
      from African Rhipicephalus spp. ticks. As well as demonstrating the applicability
      of these culture systems for studying virus-vector interactions, we provide
      preliminary evidence to support the hypothesis that SFV is not normally
      transmitted by ticks because the virus does not infect midgut cells.

PMID- 29056738
TI  - An Assessment of Epidemiology Capacity in a One Health Team at the Provincial
      Level in Thailand.
AB  - A multi-sectoral core epidemiology capacity assessment was conducted in provinces
      that implemented One Health services in order to assess the efficacy of a One
      Health approach in Thailand. In order to conduct the assessment, four provinces
      were randomly selected as a study group from a total of 19 Thai provinces that
      are currently using a One Health approach. As a control group, four additional
      provinces that never implemented a One Health approach were also sampled. The
      provincial officers were interviewed on the epidemiologic capacity of their
      respective provinces. The average score of epidemiologic capacity in the
      provinces implementing the One Health approach was 66.45%, while the provinces
      that did not implement this approach earned a score of 54.61%. The epidemiologic
      capacity of surveillance systems in provinces that utilized the One Health
      approach earned higher scores in comparison to provinces that did not implement
      the approach (75.00% vs. 53.13%, p-value 0.13). Although none of the capacity
      evaluations showed significant differences between the two groups, we found
      evidence that provinces implementing the One Health approach gained higher scores
      in both surveillance and outbreak investigation capacities. This may be explained
      by more efficient capacity when using a One Health approach, specifically in
      preventing, protecting, and responding to threats in local communities.

PMID- 29056735
TI  - Deviant Behavior: Tick-Borne Pathogens and Inflammasome Signaling.
AB  - In the face of an assault, host cells mount an immediate response orchestrated by
      innate immunity. Two of the best described innate immune signaling networks are
      the Toll- and the Nod-like receptor pathways. Extensive work has been done
      characterizing both signaling cascades with several recent advances on the
      forefront of inflammasome biology. In this review, we will discuss how more
      commonly-studied pathogens differ from tick-transmitted microbes in the context
      of Nod-like receptor signaling and inflammasome formation. Because pathogens
      transmitted by ticks have unique characteristics, we offer the opinion that these
      microbes can be used to uncover novel principles of Nod-like receptor biology.

PMID- 29056739
TI  - Intestinal Organoids-Current and Future Applications.
AB  - Recent technical advances in the stem cell field have enabled the in vitro
      generation of complex structures resembling whole organs termed organoids. Most
      of these approaches employ culture systems that allow stem cell-derived or tissue
      progenitor cells to self-organize into three-dimensional (3D)-structures. Since
      organoids can be grown from different species (human, mouse, cat, dog), organs
      (intestine, kidney, brain, liver), and from patient-derived induced pluripotent
      stem cells, they create significant prospects for modelling development and
      diseases, for toxicology and drug discovery studies, and in the field of
      regenerative medicine. Here, we report on intestinal stem cells, organoid
      culture, organoid disease modeling, transplantation, specifically covering the
      current and future uses of this exciting new insight model to the field of
      veterinary medicine.

PMID- 29056741
TI  - Regarding Tick-Borne Relapsing Fever in the Americas; Some Historical Aspects of
      a Forgotten Disease in Colombia.
AB  - In the first decades of the 20th century, scientific papers were published
      suggesting the presence of Tick-Borne Relapsing Fever in Colombia. As a
      contribution, we present some historical aspects referring to this topic.

PMID- 29056740
TI  - The Use of Recombinant Feline Interferon Omega Therapy as an Immune-Modulator in
      Cats Naturally Infected with Feline Immunodeficiency Virus: New Perspectives.
AB  - Type I interferons (IFNs) are well-known cytokines that, among their main
      functions, are key components of the host immune response against viral
      infections. Due to its immune modulation properties, they are commonly used in
      the therapeutic approach of various retroviral infections, namely human
      immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV). In HIV
      infection, it has been shown that IFN therapy limits early viral replication,
      particularly useful on post-exposure prophylaxis. In veterinary medicine,
      recombinant feline interferon omega (rFeIFN-omega) was the first interferon
      licensed for use in cats. Several studies have recently shown that this compound
      seems to stimulate the innate immunity, decreasing clinical signs and co
      infections in naturally FIV-infected cats. More than summarizing the main
      conclusions about rFeIFN-omega in cats, this review emphasizes the immune
      modulation properties of IFN therapy, opening new perspectives for its use in
      retroviral infections. Either in FIV-infected cats or in HIV individuals, type I
      IFNs seem to induce an innate immune-modulation and should not be overlooked as a
      therapeutic option in retroviral infections.

PMID- 29056742
TI  - Fluorescent Protein Expressing Rickettsia buchneri and Rickettsia peacockii for
      Tracking Symbiont-Tick Cell Interactions.
AB  - Rickettsiae of indeterminate pathogenicity are widely associated with ticks. The
      presence of these endosymbionts can confound a One Health approach to combatting
      tick-borne diseases. Genomic analyses of symbiotic rickettsiae have revealed that
      they harbor mutations in gene coding for proteins involved in rickettsial
      pathogenicity and motility. We have isolated and characterized two rickettsial
      symbionts-Rickettsia peacockii and R. buchneri-both from ticks using tick cell
      cultures. To better track these enigmatic rickettsiae in ticks and at the tick
      mammal interface we transformed the rickettsiae to express fluorescent proteins
      using shuttle vectors based on rickettsial plasmids or a transposition system
      driving insertional mutagenesis. Fluorescent protein expressing R. buchneri and
      R. peacockii will enable us to elucidate their interactions with tick and
      mammalian cells, and track their location and movement within individual cells,
      vector ticks, and host animals.

PMID- 29056743
TI  - Exfoliative Endometrial Cytology in Embryo Donor Cows-Comparison of Sampling
      Localizations for the Diagnosis of Subclinical Endometritis.
AB  - Subclinical endometritis has a major effect on the reproductive performance of
      dairy cows and also on the success of embryo collection. Thus it is important to
      minimize the number of false-negative diagnoses. In order to evaluate the
      question of whether or not a single cytobrush sample is representative of the
      whole endometrium, 53 German Holstein embryo donor cows in the northwest of
      Germany were examined via the cytobrush method at three different localizations
      of the uterus: the uterine body about 0.5 cm cranial of the cervical canal and
      both uterine horns about 1.5 cm cranial of the bifurcation. Although the mean
      percentage of polymorphonuclear neutrophils at the three locations is not
      significantly different (p = 0.64), the individual variations lead to the
      conclusion that more than one sample of the endometrium should be taken into
      account when diagnosing subclinical endometritis in embryo donor cows.

PMID- 29056744
TI  - Using Bronson Equation to Accurately Predict the Dog Brain Weight Based on Body
      Weight Parameter.
AB  - The study used 69 brains (n = 69) from adult dog cadavers, divided by their skull
      type into three groups, brachi (B), dolicho (D) and mesaticephalic (M) (n = 23
      each), and aimed: (1) to determine whether the Bronson equation may be applied,
      without reservation, to estimate brain weight (BW) in brachy (B), dolicho (D),
      and mesaticephalic (M) dog breeds; and (2) to evaluate which breeds are more
      closely related to each other in an evolutionary scenario. All subjects were
      identified by sex, age, breed, and body weight (bw). An oscillating saw was used
      for a circumferential craniotomy to open the skulls; the brains were removed and
      weighed using a digital scale. For statistical analysis, p-values < 0.05 were
      considered significant. The work demonstrated a strong relationship between the
      observed and predicted BW by using the Bronson equation. It was possible to
      hypothesize that groups B and D present a greater encephalization level than M
      breeds, that B and D dog breeds are more closely related to each other than to M,
      and from the three groups, the D individuals presented the highest brain mass
      mean.

PMID- 29056745
TI  - Sex Hormone Metabolism and Threatened Abortion.
AB  - BACKGROUND The aim of this study was to evaluate changes in sex hormone
      metabolism in patients with threatened miscarriage. MATERIAL AND METHODS We
      recruited 73 women in early pregnancy (6-8 weeks of gestation) and divided them
      into the following 2 groups based on whether they had vaginal bleeding: group A
      (n=34), the threatened abortion group; and group B (n=39), the normal pregnancy
      group. Human chorionic gonadotrophin (hCG), estradiol (E2), progesterone (P4),
      and testosterone (T) serum levels were tested and sex hormone metabolites in the
      urine were detected using gas chromatography-triple quadrupole mass spectrometry
      (GC-MS/MS). As the control, data for sex hormones and their metabolites were
      obtained in normal women of childbearing age without pregnancy (group C: n=23).
      RESULTS E2 and T serum levels were lower in women with threatened miscarriage
      (group A). Estrone (E1), E2, estriol (E3), 16alpha-hydroxyestrone (16alpha-OHE1),
      4-methoxyestrone (4-MeOE1), 2-hydroxyestradiol (2-OHE2), and 4-methoxyestradiol
      (4-MeOE2) levels were significantly lower in group A (P=0.001, 0.003, 0.009,
      0.001, 0.012, 0.032, and 0.047, respectively.). Urine levels of
      dehydroepiandrosterone (DHEA), androstenedione (A2), and the metabolite of (A2)
      were also significantly lower in group A (P=0.007, 0.009, and 0.011,
      respectively). The 2-OHE1/E1, 4-OHE1/E1, 2-MeOE1/E1, and 2-MeOE2/E2 ratios were
      lower in group B, whereas the 2-OHE2/E2, 4-OHE2/E2, and 4-MeOE2/E2 ratios were
      dramatically lower in all pregnant women (groups A and B) than in group C.
      CONCLUSIONS Deficiency in DHEA and abnormal levels of sex hormone metabolites may
      cause a reduction in the activity of estrogens in women with threatened abortion.
      These alterations may result in bleeding during the first trimester of pregnancy.

PMID- 29056746
TI  - Disabling Outcomes After Peripheral Vascular Catheter Insertion in a Newborn
      Patient: A Case of Medical Liability?
AB  - BACKGROUND The positioning of peripheral venous catheters (PVC) is an invasive
      procedure commonly performed in pediatrics hospital wards to obtain vascular
      access for the administration of fluids, medications and other intravenous (IV)
      therapies. Many studies exist about management of peripheral venous access in
      adults. On the contrary, scientific evidence on the management of this procedure
      in children and newborns, especially regarding the optimal duration of infusion
      and the possible related side effects, is still poor. To minimize the risk of
      phlebitis, the guidelines of the US Centers for Disease Control and Prevention
      suggest the replacement of the catheter every 72-96 hours in adult patients,
      while in pediatric patients the catheter can remain in place for the entire
      duration of the IV therapy, unless complications arise. CASE REPORT In the
      presented case, after the positioning of a PVC in a newborn, no clear
      signs/symptoms of phlebitis were registered before the sixth day and, despite the
      immediate removal of the catheter, the thrombotic process, secondary to
      phlebitis, was already occurring, causing serious and permanent disabling
      outcomes, susceptible to legal medical evaluation and financial compensation.
      CONCLUSIONS The knowledge of this case is particularly interesting to clinicians
      working in the field of neonatal care and to clinical risk management services
      inside hospital structures, since similar cases may be the source of requests for
      extremely high financial compensations due to medical liability.

PMID- 29056749
TI  - Trial watch: Tracing investment in drug development for Alzheimer disease.

PMID- 29056747
TI  - PRRT2 deficiency induces paroxysmal kinesigenic dyskinesia by regulating synaptic
      transmission in cerebellum.
AB  - Mutations in the proline-rich transmembrane protein 2 (PRRT2) are associated with
      paroxysmal kinesigenic dyskinesia (PKD) and several other paroxysmal neurological
      diseases, but the PRRT2 function and pathogenic mechanisms remain largely
      obscure. Here we show that PRRT2 is a presynaptic protein that interacts with
      components of the SNARE complex and downregulates its formation. Loss-of-function
      mutant mice showed PKD-like phenotypes triggered by generalized seizures,
      hyperthermia, or optogenetic stimulation of the cerebellum. Mutant mice with
      specific PRRT2 deletion in cerebellar granule cells (GCs) recapitulate the
      behavioral phenotypes seen in Prrt2-null mice. Furthermore, recording made in
      cerebellar slices showed that optogenetic stimulation of GCs results in transient
      elevation followed by suppression of Purkinje cell firing. The anticonvulsant
      drug carbamazepine used in PKD treatment also relieved PKD-like behaviors in
      mutant mice. Together, our findings identify PRRT2 as a novel regulator of the
      SNARE complex and provide a circuit mechanism underlying the PRRT2-related
      behaviors.

PMID- 29056750
TI  - Trends in Employment and Earnings of Allowed and Rejected Applicants to the
      Social Security Disability Insurance Program.

PMID- 29056748
TI  - Wnt-induced Vangl2 phosphorylation is dose-dependently required for planar cell
      polarity in mammalian development.
AB  - Planar cell polarity (PCP) is an evolutionarily conserved essential mechanism
      that provides directional information to control and coordinate polarized
      cellular and tissue behavior during embryonic development. Disruption of PCP
      leads to severe morphological defects in vertebrates and its dysregulation
      results in a variety of human diseases such as neural tube defects and skeletal
      dysplasia. PCP is governed by a set of highly conserved core proteins that are
      asymmetrically localized at the cell surface throughout the polarized tissues.
      The uniform directionality of PCP is established by global cues, such as Wg/Wnt
      signaling gradients that break the original symmetrical localization of core PCP
      proteins including Vang/Vangl and Fz/Fzd. However, the exact mechanism remains
      elusive. In this study, we found that Vangl2 phosphorylation, which was
      previously identified to be induced by Wnt5a signaling, is required for Vangl2
      functions in mammalian PCP in multiple tissues. The in vivo activities of Vangl2
      are determined by its phosphorylation level. Phospho-mutant Vangl2 exhibits
      dominant negative effects, whereas Vangl2 with reduced phosphorylation is
      hypomorphic. We show that Vangl2 phosphorylation is essential for its uniform
      polarization pattern. Moreover, serine/threonine kinases CK1E and CK1delta are
      redundantly required for Wnt5a-induced Vangl2 phosphorylation. Dvl family members
      are also required for Wnt5a-induced Vangl2 phosphorylation by enhancing the
      interaction of CK1 and Vangl2. These findings demonstrate that induction of Vangl
      protein phosphorylation plays an essential role in transducing Wnt5a signaling to
      establish PCP in mammalian development, suggesting a phosphorylation-regulated
      "Vangl activity gradient" model in addition to the well-documented "Fz activity
      gradient" model in Wnt/PCP signaling.

PMID- 29056752
TI  - Quantitative Scanning Probe Microscopy for Nanomechanical Forensics.
AB  - Atomic force microscopy (AFM) was used to assess the indentation modulus Ms and
      pull-off force Fpo in four case studies of distinct evidence types, namely hair,
      questioned documents, fingerprints, and explosive particle-surface interactions.
      In the hair study, Ms decreased and Fpo increased after adding conditioner and
      bleach to the hair. For the questioned documents, Ms and Fpo of two inks were
      markedly different; ballpoint pen ink exhibited smaller variations relative to
      the mean value than printer ink. The fingerprint case study revealed that both
      maximum height and Fpo decreased over a three-day period. Finally, the study on
      explosive particle-surface interactions illustrated that two fabrics exhibited
      similar Ms, but different Fpo. Overall, it was found that AFM addresses needs in
      forensic science as defined by several federal agencies, in particular an
      improved ability to expand the information extracted from evidence and to
      quantify its evidentiary value.

PMID- 29056751
TI  - A Brain Motivated to Play: Insights into the Neurobiology of Playfulness.
AB  - Play is an important part of normal childhood development and is seen in varied
      forms among many mammals. While not indispensable to normal development, playful
      social experiences as juveniles may provide an opportunity to develop flexible
      behavioral strategies when novel and uncertain situations arise as an adult. To
      understand the neurobiological mechanisms responsible for play and how the
      functions of play may relate to these neural substrates, the rat has become the
      model of choice. Play in the rat is easily quantified, tightly regulated, and can
      be modulated by genetic factors and postnatal experiences. Brain areas most
      likely to be involved in the modulation of play include regions within the
      prefrontal cortex, dorsal and ventral striatum, some regions of the amygdala, and
      habenula. This paper discusses what we currently know about the neurobiological
      substrates of play and how this can help illuminate functional questions about
      the putative benefits of play.

PMID- 29056753
TI  - Post-normal institutional identities: Quality assurance, reflexivity and ethos of
      care.
AB  - This paper suggests adopting a 'post-normal science' (PNS) style and practice in
      scientific advice, and motivate the urgency of this methodological stance with
      the increasing complexity, and polarisation affecting the use of science-based
      evidence for policy. We reflect on challenges and opportunities faced by a
      'boundary organisation' that interfaces between science and policy, taking as
      example the European Commission's Directorate General Joint Research Centre,
      whose mission is stated as that to be the "in-house science service". We suggest
      that such an institution can be exemplary as to what could be changed to improve
      the quality of evidence feeding into the policy processes in the European Union.
      This paper suggests how an in-house culture of reflexivity and humility could
      trigger changes in the existing styles and methods of scientific governance; at
      the JRC, taken as example, this would mean opening up to the existing plurality
      of norms and styles of scientific inquiry, and adopting more participatory
      approaches of knowledge production, assessment and governance. We submit that the
      institutional changes advocated here are desirable and urgent in order to
      confront the ongoing erosion of trust in 'evidence based policy', anticipating
      controversies before they become evident in the institutional setting in which
      institutions operate.

PMID- 29056754
TI  - Subcutaneous Photovoltaic Infrared Energy Harvesting for Bio-Implantable Devices.
AB  - Wireless biomedical implantable devices on the mm-scale enable a wide range of
      applications for human health, safety, and identification, though energy
      harvesting and power generation are still looming challenges that impede their
      widespread application. Energy scavenging approaches to power biomedical implants
      have included thermal [1-3], kinetic [4-6], radio-frequency [7-11] and radiative
      sources [12-14]. However, the achievement of efficient energy scavenging for
      biomedical implants at the mm-scale has been elusive. Here we show that
      photovoltaic cells at the mm-scale can achieve a power conversion efficiency of
      more than 17 % for silicon and 31 % for GaAs under 1.06 MUW/mm2 infrared
      irradiation at 850 nm. Finally, these photovoltaic cells demonstrate highly
      efficient energy harvesting through biological tissue from ambient sunlight, or
      irradiation from infrared sources such as used in present-day surveillance
      systems, by utilizing the near infrared (NIR) transparency window between the 650
      nm and 950 nm wavelength range [15-17].

PMID- 29056755
TI  - Father's Labour Migration and Children's School Discontinuation in Rural
      Mozambique.
AB  - We examine how the discontinuation of schooling among left-behind children is
      related to multiple dimensions of male labor migration: the accumulation of
      migration experience, the timing of these migration experiences in the child's
      life course, and the economic success of the migration. Our setting is rural
      southern Mozambique, an impoverished area with massive male labor out-migration.
      Results show that fathers' economically successful labor migration is more
      beneficial for children's schooling than unsuccessful migration or non-migration.
      There are large differences, however, by gender: compared to sons of non
      migrants, sons of migrant fathers (regardless of migration success) have lower
      rates of school discontinuation, while daughters of migrant fathers have rates of
      school discontinuation no different than daughters of non-migrants. Furthermore,
      accumulated labor migration across the child's life course is beneficial for
      boys' schooling, but not girls'. Remittances sent in the past year reduce the
      rate of discontinuation for sons, but not daughters.

PMID- 29056757
TI  - Student Perceptions of Online Homework Use for Formative Assessment of Learning
      in Organic Chemistry.
AB  - Use of online homework as a formative assessment tool for organic chemistry
      coursework was examined. Student perceptions of online homework in terms of (i)
      its ranking relative to other course aspects, (ii) their learning of organic
      chemistry, and (iii) whether it improved their study habits and how students used
      it as a learning tool were investigated. Our students perceived the online
      homework as one of the more useful course aspects for learning organic chemistry
      content. We found a moderate and statistically significant correlation between
      online homework performance and final grade. Gender as a variable was ruled out
      since significant gender differences in overall attitude toward online homework
      use and course success rates were not found. Our students expressed relatively
      positive attitudes toward use of online homework with a majority indicating
      improved study habits (e.g., study in a more consistent manner). Our students
      used a variety of resources to remediate incorrect responses (e.g., class
      materials, general online materials, and help from others). However, 39% of our
      students admitted to guessing at times, instead of working to remediate incorrect
      responses. In large enrollment organic chemistry courses, online homework may act
      to bridge the student-instructor gap by providing students with a supportive
      mechanism for regulated learning of content.

PMID- 29056756
TI  - Approaches for calculating solvation free energies and enthalpies demonstrated
      with an update of the FreeSolv database.
AB  - Solvation free energies can now be calculated precisely from molecular
      simulations, providing a valuable test of the energy functions underlying these
      simulations. Here, we briefly review "alchemical" approaches for calculating the
      solvation free energies of small, neutral organic molecules from molecular
      simulations, and illustrate by applying them to calculate aqueous solvation free
      energies (hydration free energies). These approaches use a non-physical pathway
      to compute free energy differences from a simulation or set of simulations and
      appear to be a particularly robust and general-purpose approach for this task. We
      also present an update (version 0.5) to our FreeSolv database of experimental and
      calculated hydration free energies of neutral compounds and provide input files
      in formats for several simulation packages. This revision to FreeSolv provides
      calculated values generated with a single protocol and software version, rather
      than the heterogeneous protocols used in the prior version of the database. We
      also further update the database to provide calculated enthalpies and entropies
      of hydration and some experimental enthalpies and entropies, as well as
      electrostatic and nonpolar components of solvation free energies.

PMID- 29056758
TI  - Disclosure Stress, Social Support, and Depressive Symptoms Among Cisgender
      Bisexual Youth.
AB  - Bisexual youth are at elevated risk for depression compared to lesbians and gay
      men. Research on bisexual stigma suggests these youth are uniquely vulnerable to
      stress related to sexual identity disclosure. Depression associated with this
      stress may be buffered by social support from parents and friends. We examined
      the differential influence of social support from parents and friends (Child and
      Adolescent Social Support Scale) on the relation between disclosure stress (LGBTQ
      Coming Out Stress Scale) and depressive symptoms (Beck Depression Inventory) and
      differences by gender in a sample of cisgender bisexual youth (n = 383) using
      structural equation modeling. Parental support buffered the association between
      stressful disclosure to family and depressive symptoms, especially for bisexual
      men; bisexual women seemed not to benefit from such support when disclosure
      stress was high. This nuanced examination elucidates the ways family members and
      clinicians can best support bisexual youth sexual identity disclosure.

PMID- 29056760
TI  - Dynamic Surface Enrichment in Drying Thin-Film Binary Polymer Solutions.
AB  - Solution-cast, thin-film polymer composites find a wide range of applications,
      such as in the photoactive layer of organic solar cells. The performance of this
      layer crucially relies on its phase-separated morphology. Efficient charge
      carrier extraction requires each of the components to preferentially wet one of
      the two electrodes. It is often presumed that the experimentally observed surface
      enrichment required for this is caused by specific interactions of the active
      ingredients with each surface. By applying a generalized diffusion model, we find
      the dynamics to also play an important role in determining which component
      accumulates at which surface. We show that for sufficiently fast evaporation the
      component with the smallest cooperative diffusivity accumulates at the free
      interface. Counterintuitively, depending on the interactions between the various
      components, this may be the smaller solute. Our comprehensive numerical and
      analytical study provides a tool to predict and control phase-separated
      morphologies in thin-film polymer composites.

PMID- 29056759
TI  - Optimisation of lithium-substituted bioactive glasses to tailor cell response for
      hard tissue repair.
AB  - Bioactive glasses (BG) are used clinically because they can both bond to hard
      tissue and release therapeutic ions that can stimulate nearby cells. Lithium has
      been shown to regulate the Wnt/beta-catenin cell signalling pathway, which plays
      important roles in the formation and repair of bone and teeth. Lithium-releasing
      BG, therefore, have the potential to locally regulate hard tissue formation;
      however, their design must be tailored to induce an appropriate biological
      response. Here, we optimised the release of lithium from lithium-substituted BG
      by varying BG composition, particle size and concentration to minimise toxicity
      and maximise upregulation of the Wnt target gene Axin2 in in vitro cell cultures.
      Our results show that we can tailor lithium release from BG over a wide
      therapeutic and non-toxic range. Increasing the concentration of BG in cell
      culture medium can induce toxicity, likely due to modulations in pH.
      Nevertheless, at sub-toxic concentrations, lithium released from BG can
      upregulate the Wnt pathway in 17IA4 cells, similarly to treatment with LiCl.
      Taken together, these data demonstrate that ion release from lithium-substituted
      BG can be tailored to maximise biological response. These data may be important
      in the design of BG that can regulate the Wnt/beta-catenin pathway to promote
      hard tissue repair or regeneration.

PMID- 29056762
TI  - Spectral model selection in the electronic measurement of the Boltzmann constant
      by Johnson noise thermometry.
AB  - In the electronic measurement of the Boltzmann constant based on Johnson noise
      thermometry, the ratio of the power spectral densities of thermal noise across a
      resistor at the triple point of water, and pseudo-random noise synthetically
      generated by a quantum-accurate voltage-noise source is constant to within 1 part
      in a billion for frequencies up to 1 GHz. Given knowledge of this ratio, and the
      values of other parameters that are known or measured, one can determine the
      Boltzmann constant. Due, in part, to mismatch between transmission lines, the
      experimental ratio spectrum varies with frequency. We model this spectrum as an
      even polynomial function of frequency where the constant term in the polynomial
      determines the Boltzmann constant. When determining this constant (offset) from
      experimental data, the assumed complexity of the ratio spectrum model and the
      maximum frequency analyzed (fitting bandwidth) dramatically affects results.
      Here, we select the complexity of the model by cross-validation - a data-driven
      statistical learning method. For each of many fitting bandwidths, we determine
      the component of uncertainty of the offset term that accounts for random and
      systematic effects associated with imperfect knowledge of model complexity. We
      select the fitting bandwidth that minimizes this uncertainty. In the most recent
      measurement of the Boltzmann constant, results were determined, in part, by
      application of an earlier version of the method described here. Here, we extend
      the earlier analysis by considering a broader range of fitting bandwidths and
      quantify an additional component of uncertainty that accounts for imperfect
      performance of our fitting bandwidth selection method. For idealized simulated
      data with additive noise similar to experimental data, our method correctly
      selects the true complexity of the ratio spectrum model for all cases considered.
      A new analysis of data from the recent experiment yields evidence for a temporal
      trend in the offset parameters.

PMID- 29056761
TI  - Disruption of doubly uniparental inheritance of mitochondrial DNA associated with
      hybridization area of European Mytilus edulis and Mytilus trossulus in Norway.
AB  - Doubly uniparental inheritance of mitochondria (DUI) is best known in the blue
      mussel Mytilus. Under this model, two types of mitochondrial DNA exist: female
      type (F), transmitted from females to offspring of both genders, and male type
      (M), transmitted exclusively from males to sons. The mitogenomes are usually
      highly divergent, but an occasional replacement of a typical M genome by a
      particular F genome has been postulated to explain reduction of this divergence.
      Disruption of the DUI model has been reported in hybridization areas. Here, we
      present a new case of DUI disruption in a hybrid M. trossulus/M. edulis
      population from the North Sea (Norway). No M haplotypes derived from M. trossulus
      were identified in this population. Typical M haplotypes derived from M. edulis
      (ME) were rare. Two F-type haplogroups were found: one derived from M. edulis
      (FE) and the second derived from M. trossulus (FT). Many haplotypes from the FT
      group were recombinants, with the male CR sequence coming from the M. trossulus
      genome (FT1 haplogroup) in contrast to M. edulis CR as in the Baltic. FT1
      haplotypes were abundant in the studied population, including homoplasmic
      females. However, males significantly more often carried these haplotypes;
      therefore, male heteroplasmy involved the original FE and recombinant FT,
      indicating that the FT genome undergoes masculinization. Structural similarity of
      FT1 CR with previously reported, masculinized Baltic haplotypes, which were
      derived from FE/ME recombination, provides further evidence that CR M-F
      recombination is a prerequisite for masculinization, also in the context of
      native M. trossulus mtDNA.

PMID- 29056763
TI  - A Boltzmann Constant Determination Based on Johnson Noise Thermometry.
AB  - A value for the Boltzmann constant was measured electronically using an improved
      version of the Johnson Noise Thermometry (JNT) system at the National Institute
      of Standards and Technology (NIST), USA. This system is different from prior
      ones, including those from the 2011 determination at NIST and both 2015 and 2017
      determinations at the National Institute of Metrology (NIM), China. As in all
      three previous determinations, the main contribution to the combined uncertainty
      is the statistical uncertainty in the noise measurement, which is mitigated by
      accumulating and integrating many weeks of cross-correlated measured data. The
      second major uncertainty contribution also still results from variations in the
      frequency response of the ratio of the measured spectral noise of the two noise
      sources, the sense resistor at the triple-point of water and the superconducting
      quantum voltage noise source. In this paper, we briefly describe the major
      differences between our JNT system and previous systems, in particular the input
      circuit and approach we used to match the frequency responses of the two noise
      sources. After analyzing and integrating 49 days of accumulated data, we
      determined a value: k = 1.380 642 9(69)*10-23 J/K with a relative standard
      uncertainty of 5.0*10-6 and relative offset -4.05*10-6 from the CODATA 2014
      recommended value.

PMID- 29056764
TI  - Religious and Spiritual Journeys: Brief Reflections from Mothers and Fathers in a
      Neonatal Intensive Care Unit (NICU).
AB  - The birth of a child is often accompanied by elation and celebration, but when a
      birth results in admittance to the Neonatal Intensive Care Unit (NICU), the
      typical emotions of joy and celebration may be tempered with anxiety and fear.
      Parents with a religious and spiritual worldview may find their faith and
      spiritual lens is an important aspect of coping with their NICU experience. There
      is a dearth of literature on this issue, and thus a pilot study was implemented
      that included eight mothers and fathers of babies admitted to the NICU. Parents
      responded to a brief interview 4 to 6 weeks after discharge that focused on how
      their religious or spiritual worldview changed as a result of their NICU
      experience, how they coped with their premature newborn after discharge, and the
      perceived impact on their spousal/partner relation-ship. Results indicated that
      parents who presented to the NICU with a religious or spiritual background
      indicated their faith grew as a result of their experience in the NICU. Parents
      without a religious or spiritual worldview also reported being able to adequately
      manage their NICU experience and reported little to no change in their religious
      or spiritual lives. Further, parents reported they coped well after their babies'
      discharge from the NICU and had supportive spousal relationships. This pilot
      study supported assessment of religious and spiritual experiences as a salient
      aspect in NICU parents' lives. Further study is necessary to elucidate how
      religiosity and spirituality can be strengthened for families during this
      challenging time.

PMID- 29056765
TI  - Improving Photometric Calibration of Meteor Video Camera Systems.
AB  - We present the results of new calibration tests performed by the NASA Meteoroid
      Environment Office (MEO) designed to help quantify and minimize systematic
      uncertainties in meteor photometry from video camera observations. These
      systematic uncertainties can be categorized by two main sources: an imperfect
      understanding of the linearity correction for the MEO's Watec 902H2 Ultimate
      video cameras and uncertainties in meteor magnitudes arising from transformations
      between the Watec camera's Sony EX-View HAD bandpass and the bandpasses used to
      determine reference star magnitudes. To address the first point, we have measured
      the linearity response of the MEO's standard meteor video cameras using two
      independent laboratory tests on eight cameras. Our empirically determined
      linearity correction is critical for performing accurate photometry at low camera
      intensity levels. With regards to the second point, we have calculated synthetic
      magnitudes in the EX bandpass for reference stars. These synthetic magnitudes
      enable direct calculations of the meteor's photometric flux within the camera
      band pass without requiring any assumptions of its spectral energy distribution.
      Systematic uncertainties in the synthetic magnitudes of individual reference
      stars are estimated at ~ 0.20 mag, and are limited by the available spectral
      information in the reference catalogs. These two improvements allow for zero
      points accurate to ~ 0.05 - 0.10 mag in both filtered and unfiltered camera
      observations with no evidence for lingering systematics. These improvements are
      essential to accurately measuring photometric masses of individual meteors and
      source mass indexes.

PMID- 29056766
TI  - Monitoring cocaine use and abstinence among cocaine users for contingency
      management interventions.
AB  - During contingency management interventions, reinforcement of cocaine abstinence
      is arranged by delivering an incentive when a urine sample tests cocaine
      negative. The use of qualitative versus quantitative urinalysis testing may have
      important implications for effects on cocaine abstinence. Qualitative testing
      (i.e., testing that solely identifies whether a particular substance is present
      or absent) may not detect short-term cocaine abstinence because a single instance
      of cocaine use can result in cocaine-positive urine over many days. Quantitative
      testing (i.e., testing that identifies how much of a substance is present) may be
      more sensitive to short-term cocaine abstinence; however, the selection of a
      criterion for distinguishing new use versus carryover from previous use is an
      important consideration. The present study examined benzoylecgonine
      concentrations, the primary metabolite of cocaine, in urine samples collected
      three times per week for 30 weeks from 28 cocaine users who were exposed to a
      cocaine abstinence contingency. Of the positive urine samples (benzoylecgonine
      concentration >300 ng/ml), 29%, 21%, 14%, and 5% of the samples decreased in
      benzoylecgonine concentration by more than 20%, 40%, 60%, and 80% per day,
      respectively. As the size of the decrease increased, the likelihood of that
      sample occurring during a period leading to a cocaine-negative urine sample
      (benzoylecgonine concentration <=300 ng/ml) also increased. The number of days
      required to produce a cocaine-negative sample following a positive sample ranged
      from 1 to 10 days and was significantly correlated with the starting
      benzoylecgonine level (r = 0.43, p < 0.001). The present analyses may aid in the
      development of procedures that allow for the precise reinforcement of recent
      cocaine abstinence during contingency management interventions.

PMID- 29056767
TI  - Cross-commodity delay discounting of alcohol and money in alcohol users.
AB  - Despite real-world implications, the pattern of delay discounting in alcohol
      users when the commodities now and later differ has not been well characterized.
      In this study, 60 participants on Amazon's Mechanical Turk completed the Alcohol
      Use Disorder Identification Test (AUDIT) to assess severity of use and completed
      four delay discounting tasks between hypothetical, equivalent amounts of alcohol
      and money available at five delays. The tasks included two cross-commodity
      (alcohol now-money later and money now-alcohol later) and two same-commodity
      (money now-money later and alcohol now-alcohol later) conditions. Delay
      discounting was significantly associated with clinical cutoffs of the AUDIT for
      both of the cross-commodity conditions but not for either of the same-commodity
      delay discounting tasks. The cross-commodity discounting conditions were related
      to severity of use wherein heavy users discounted future alcohol less and future
      money more. The change in direction of the discounting effect was dependent on
      the commodity that was distally available suggesting a distinctive pattern of
      discounting across commodities when comparing light and heavy alcohol users.

PMID- 29056768
TI  - Signet-ring cell adenoma of the thyroid and rheumatoid arthritis: incidental
      association or methotrexate-related change?

PMID- 29056769
TI  - Disease activity in axial spondyloarthritis after discontinuation of TNF
      inhibitors therapy.
AB  - OBJECTIVE: Use of tumour necrosis factor inhibitors (TNFi) has proved to be an
      important step forward in the treatment of axial spondyloarthritis (axSpA), but
      the duration of the therapy as well as the management in case of low disease
      activity (LDA) or remission are not clearly established. Currently, the
      identification of potential predictors associated with the treatment
      discontinuation is the basic purpose of many clinical studies. The aim of this
      study was to analyze the influence of the discontinuation of TNFi therapy on the
      disease activity in patients with low disease activity. MATERIAL AND METHODS: The
      study included 65 patients; 47 of patients (72%) were treated with etanercept, 16
      (2%) with adalimumab and 2 (3%) with infliximab. RESULTS: The mean age of the
      patients was 45 years, the mean BASDAI score was 6.8 and VAS for low back pain
      was 76 mm at baseline. 54 patients with axSpA (83%) achieved LDA after 9 months
      of anti-TNF therapy. During follow-up 40 patients (74% of patients with LDA) had
      an increase of the disease activity after mean 14 weeks and needed to restart the
      treatment with TNFi. After restart of the therapy LDA was regained in all
      patients after mean 7 weeks. 11 patients (17%) have never achieved LDA and 14
      patients (22%) had LDA longer than 6 months without relapse. At baseline higher
      levels of CRP and ESR were observed in patients with relapse of the disease at
      the end of treatment and with LDA shorter than 6 months. CONCLUSIONS: Changes in
      the values of disease activity indicators (CRP, ESR) correlated with more stable
      response to TNFi therapy. Over 50% of patients who were treated with TNFi needed
      to restart the therapy. Treatment resumption allowed to regain a good clinical
      effect among affected patients.

PMID- 29056770
TI  - Assessment of hospitalization and mortality of scleroderma in-patients: a
      thirteen-year study.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is an uncommon non-hereditary sporadic
      disease that increases the risk of premature death, especially in diffuse type.
      We determined the prevalence of SSc in the last 13 years in our rheumatologic
      hospitals as a referral center for southern Iranian patients, the causes of
      hospitalization, the average length of stay (LOS), the mortality rate, and the
      reason for their mortality. MATERIAL AND METHODS: A cross-sectional study was
      performed in Shiraz University of Medical Sciences, Iran. The studied population
      included all patients diagnosed with systemic sclerosis. We calculated the
      hospitalization rates, in-hospital mortality rates, and mean LOS. RESULTS: There
      were 446 admissions by 181 patients with SSc. The female to male ratio was about
      10.7 : 1. The overall mean LOS was 5.95 days. Digital ulcer and interstitial lung
      disease (ILD) were the most common causes of hospitalizations among the SSc
      related events. For those with a non-SSc-related condition, infection was the
      most prevalent event. Most of the deaths were due to ILD and pulmonary artery
      hypertension(PAH), and the overall in-hospital mortality rate was 16.5%.
      CONCLUSIONS: Women with SSc had higher rates of hospitalization but lower in
      hospital mortality than men.There were some differences between our study and
      other similar studies in the causes of hospitalization and in-hospital death
      among SSc patients, especially the lower age of death. The patients with digital
      ulcers and those with intestinal lung disease or pulmonary hipertension were most
      commonly admitted to the hospital in our study group. Probably, increasing the
      skin care of these patients and asking other specialty groups to cooperate will
      decrease the high rate of hospitalizations in our population.

PMID- 29056771
TI  - Diagnostic delays in rheumatic diseases with associated arthritis.
AB  - OBJECTIVE: The objective of this study was to determine the length of delay in
      diagnosis of inflammatory rheumatic diseases, and to indicate the main factors
      responsible for such delays. MATERIAL AND METHODS: A retrospective multi-centre
      questionnaire survey carried out among 197 patients with diagnosed inflammatory
      rheumatic diseases or undergoing the diagnostic process. RESULTS: The most common
      early symptoms of inflammatory rheumatic disease included joint pain (94%), joint
      swelling (78%), morning joint stiffness (77%), fatigue (76%), and sleep disturbed
      by joint pain (74%). When asked about the reasons for seeking medical help, most
      patients indicated intensification of the symptoms (89%) and the fact that the
      symptoms made them unable to perform daily activities or work (86%). Limited
      access to specialists (70%) and the conviction that the symptoms will resolve
      spontaneously (57%) had the biggest impact on delaying a visit to a doctor.
      Before visiting a rheumatologist, the patients consulted their symptoms with
      their general practitioners (GPs, 95%), orthopaedicians (43%), and neurologists
      (29%). Almost half of the patients (48%) consulted their symptoms with at least 2
      non-rheumatologists, whereas as many as 21% of patients visited 4 or more
      specialists. After the onset of symptoms of rheumatic disease, 28% of patients
      delayed seeing any doctor for 4 months or longer. 36% of patients waited 4 months
      or longer for a referral to a rheumatologist. The great majority of the patients
      (85%) made an appointment with a rheumatologist within a month of receiving a
      referral. 25% of patients waited 4 months or longer to see a rheumatologist.
      CONCLUSIONS: Diagnostic delays result from both the level of patients' awareness
      (ignoring early symptoms) and improper functioning of the health care system. In
      the case of the health care system, the source of delays is not only "queues to
      rheumatologists", but also referring patients to non-rheumatologists.

PMID- 29056772
TI  - The role of ultrasonography in monitoring long-standing rheumatoid arthritis: a
      pilot study.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a condition that poses many diagnostic
      problems. As a result, it is often diagnosed too late, which makes effective
      treatment more difficult. The course of the disease is chronic, and it causes
      irreversible changes in the musculoskeletal system, as well as bone destruction,
      and this in turn impairs the proper monitoring of the treatment. Therefore, in
      order to assess the treatment's efficacy, as well as a clinical examination of
      the patient and laboratory tests, diagnostic imaging is being used more
      frequently in routine practice. The aim of this paper is to assess the usefulness
      of power Doppler ultrasonography in the assessment of MCP joints in patients with
      chronic RA (LSRA), in comparison with DAS28, X-ray, and MRI. MATERIAL AND
      METHODS: The study involved 26 patients with LSRA, treated with biologics. It
      lasted for a year. At the moment of enrolment, the condition had lasted for a
      minimum of 5 years, and DAS28 was > 5.1. The patients had visits every three
      months. During every visit, a PDUS test was performed and the DAS28 was
      determined. In the first and last month of the study the patients underwent X-ray
      and MRI tests. RESULTS: At the end of the study, the DAS28 of 26 (100%) patients
      was lower or equal to 3.2. Based on PDUS and MRI tests, no synovitis was found in
      21 (81%) and 18 (69%) patients, respectively. According to the MRI results,
      radiological changes progressed in 5 (19%) of them. All patients who showed
      progress of radiological changes also had visible synovitis during their PDUS
      test. CONCLUSIONS: PDUS in patients with LSRA can be helpful in selecting
      patients, who are likely to develop a progression of radiological changes.

PMID- 29056773
TI  - Investigating mental health in patients with osteoarthritis and its relationship
      with some clinical and demographic factors.
AB  - OBJECTIVE: The reduction in the level of mental health, particularly depression
      is associated with outcome of treatment in patients with osteoarthritis (OA).
      There is no broader research into mental health or mental health care for OA
      patients. The purpose of the present study was to determine mental health and its
      relationship with some clinical and demographic factors among patients with OA.
      MATERIAL AND METHODS: 94 patients with osteoarthritis were included in presented
      study. Patients were referred to hospital during the year of 2016, 30 male
      patients (31.9%) and 64 female (68.1%), female/male ratio was about 2 : 1. All
      patients were evaluated in the term of mental health through demographic
      questionnaire and SCL-90R questionnaire and the obtained data were analyzed using
      version 22 of SPSS Software. RESULTS: The results showed that 58.5% of patients
      with osteoarthritis had mental health disorders. Among all studied patients
      mental health disorders were found in 55 patients (58.5%), including both
      isolated and complex disorders such as: psychological discomfort in the form of
      somatic symptoms disorder (n = 45), obsessive compulsive disorders (n = 43),
      interpersonal sensitivity (n = 44), depression (n = 47), anxiety (n = 41),
      aggression (n = 52), phobia (n = 42), paranoid psychosis (n = 32), psychosis (n =
      3). In addition, the prevalence of mental health problems in patients with OA was
      significantly higher at the age range of 18 to 20 years old (p = 0.002). Also
      revealed that the greater risk of mental health disorders is in the first months
      of diagnosis of OA compare to the patients with longer disease duration more than
      six months (p = 0.01) and patients taking corticosteroids were significantly
      higher risk of mental health disorders development (p = 0.00). CONCLUSION: In
      presented study although the prevalence of OA is higher in group of older people,
      but psychiatric disorders is more common in OA patients with age range below 20
      years. In addition, patients in the early months of OA are at greater risk of
      psychiatric disorders which the disorders were observed higher in patients taking
      corticosteroids.

PMID- 29056774
TI  - Glucocorticoid management in rheumatoid arthritis: morning or night low dose?
AB  - Morning symptoms of rheumatoid arthritis (RA) are linked to circadian increase of
      night inflammation, supported by inadequate cortisol secretion in active disease.
      Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR
      and ACR from the beginning of the diagnosis, since may partially act like a
      "replacement therapy". In addition, the prevention/treatment of the night up
      regulation of the immune/inflammatory reaction has been shown more effective when
      exogenous glucocorticoid administration is managed with a night-time-release
      formulation. Despite a considerably higher cost than conventional prednisone
      (immediate release), chronotherapy with night-time-release prednisone has been
      recognized a cost-effective option for RA patients not on glucocorticoids who are
      eligible for therapy with biologic disease-modifying antirheumatic drugs
      (DMARDs). Interestingly, since different cell populations involved in the
      inflammatory process are particularly activated during the night (i.e. monocytes,
      macrophages), other therapeutical approaches used in RA, such as conventional
      DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs) should follow the same
      concepts of glucocorticoid chronotherapy. Therefore, bedtime methotrexate
      chronotherapy was found to better manage RA symptoms, and several available
      NSAIDs (i.e. indomethacin, aceclofenac, ketoprofen, flurbiprofen, lornoxicam)
      have been recently modified in their formulation, in order to obtain more focused
      night action.

PMID- 29056775
TI  - Complex diagnostics of common conditions of the motor organ of the developmental
      age.
AB  - Some muscular and osteoarticular diseases pose serious diagnostic problems, e.g.
      subsequent recurrent or persistent conditions of isolated pain in the
      extremities, most frequently - in the lower extremities, especially knee joints,
      and isolated pain in the back, usually in the lumbosacral spine. They are often
      accompanied by gait abnormalities. The paper herein presents a complex
      differential diagnosis of these conditions, the presented diseases that can cause
      them, and the role of the family doctor, paediatrician, orthopaedist, and
      rheumatologist in the diagnosis. A detailed history of the presented complaints,
      accurate physical examination, plus extensive biochemical and immunological
      diagnostics, and microbiological and imaging techniques usually allow a diagnosis
      to be made. Attention was paid to the sequence of imaging procedures conducted in
      the differential diagnosis of pains of the extremities and the spine and not to
      overuse procedures that involve exposure to ionising radiation.

PMID- 29056776
TI  - Cervical spine instability in the course of rheumatoid arthritis - imaging
      methods.
AB  - Cervical spine is affected in more than a half of patients with rheumatoid
      arthritis (RA). Depending on the degree of damage to the individual joints and
      ligaments RA-related cervical spine instability takes the form of atlanto-axial
      subluxation, subaxial subluxation or cranial settling. In the advanced cases
      spinal stenosis can occur as well as spinal cord injuries with typical
      neurological symptoms. The identification of patients with cervical spine
      instability before the occurrence of neurological complications still constitutes
      a diagnostic challenge. The article presents the methods of cervical spine
      imaging with the use of plain radiographs, magnetic resonance imaging (MRI) and
      computed tomography (CT). We discuss the advantages and disadvantages associated
      with each method and the possibility of its application in the diagnosis of
      cervical spine instability in RA. The knowledge of the above mentioned issues is
      indispensable to select an appropriate time for surgical intervention.

PMID- 29056777
TI  - Relapsing granulomatosis with polyangiitis with severe lung and upper respiratory
      tract involvement successfully treated with rituximab.
AB  - Granulomatosis with polyangiitis (GPA) is a chronic, relapsing, primary systemic
      small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies.
      The disease is characterised by the involvement of various organs. The relapse
      rate rises from about 20% at 12 months to about 60% at 5 years. The combination
      of glucocorticoids and cyclophosphamide remains the standard therapy for patients
      with generalised GPA; nevertheless, some patients do not respond satisfactorily
      to this treatment. According to EULAR-EDTA recommendations for the management of
      ANCA-associated vasculitis, RTX should be considered for remission-induction of
      new-onset as well as major relapse of organ-threatening or life-threatening GPA.
      Here we present a 35-year-old patient with relapsing GPA successfully treated
      with RTX. We also highlight the infectious complications of immunosuppressive
      treatment.

PMID- 29056778
TI  - CURVATURE-DRIVEN MOLECULAR FLOW ON MEMBRANE SURFACE.
AB  - This work presents a mathematical model for the localization of multiple species
      of diffusion molecules on membrane surfaces. Morphological change of bilayer
      membrane in vivo is generally modulated by proteins. Most of these modulations
      are associated with the localization of related proteins in the crowded lipid
      environments. We start with the energetic description of the distributions of
      molecules on curved membrane surface, and define the spontaneous curvature of
      bilayer membrane as a function of the molecule concentrations on membrane
      surfaces. A drift-diffusion equation governs the gradient flow of the surface
      molecule concentrations. We recast the energetic formulation and the related
      governing equations by using an Eulerian phase field description to define
      membrane morphology. Computational simulations with the proposed mathematical
      model and related numerical techniques predict (i) the molecular localization on
      static membrane surfaces at locations with preferred mean curvatures, and (ii)
      the generation of preferred mean curvature which in turn drives the molecular
      localization.

PMID- 29056779
TI  - Synthesis of indolo[4,3-bc]phenanthridine-6,11(2H,12H)-diones using the Schiff
      base-homophthalic anhydride cyclization reaction.
AB  - A novel indolophenanthridine ring system has been synthesized via the Schiff base
      homophthalic anhydride cyclization followed by thionyl chloride-mediated
      dehydrogenation and intramolecular Friedel-Crafts acylation. This adds to the
      array of heterocyclic systems that are available through the cycloaddition
      reaction of imines with cyclic dicarboxylic acid anhydrides. The cytotoxicities
      of the indolophenanthridines were investigated in human cancer cell cultures, and
      the results documented significant antitumor activity in a variety of human
      cancer cell lines. This provides a new heterocyclic scaffold for anticancer drug
      design.

PMID- 29056780
TI  - Asymmetric solution-phase mixture aldol reaction using oligomeric ethylene glycol
      tagged chiral oxazolidinones.
AB  - Sorting tags are oligomeric structures that can be used as protecting groups or
      chiral auxiliaries enabling solution-phase mixture syntheses of multiple tagged
      compounds in one pot and allowing for facile and predictable chromatographic
      separation of products at the end of synthetic sequences. Perfluorinated
      hydrocarbon and oligomeric ethylene glycol (OEG) derivatives are known classes of
      sorting tags. Herein we describe the preparation of OEGylated chiral
      oxazolidinones and their use in asymmetric solution-phase mixture aldol
      reactions. Through the use of such oxazolidinones based on tyrosine four
      different individually tagged aldol adducts were obtained as a mixture,
      chromatographically demixed, detagged, and it was shown that these processes gave
      the desired aldol products in good yield and enantioselectivity.

PMID- 29056781
TI  - The Effect of Sporting Events on Medical Transport Time at a Level 1 Trauma
      Center: a Retrospective Cohort Study.
AB  - OBJECTIVE: We investigate how West Virginia University football games affect
      transport to Ruby Memorial Hospital, which shares a parking lot with Milan Puskar
      Football Stadium. METHODS: A retrospective chart review of a trauma registry from
      a level 1-trauma center was conducted from 2007 to 2011 for all home and away
      football games. Home games served as time period of interest and away games
      served as a control time period. Patient charts were collected for a 36-hour time
      window surrounding the game. 250 patient charts were complete for home games and
      185 patient charts for away games. Data analyzed were time from scene to arrival
      at hospital, use of air transport, transport time in relation to kick-off, and
      comparison between demographic and emergency department disposition of patients
      arriving during home games vs. patients arriving during away games. RESULTS: No
      statistically significant differences were found for demographic data or
      emergency department disposition between groups. For ground transport directly
      from scene, the average time to arrival at the hospital was 44.9 minutes for home
      games and 45.1 minutes for away games. For air transport directly from the scene,
      the average time to arrival at the hospital was 44.9 minutes for home games and
      44.0 minutes for away games. For ground transfer from another facility, the
      average time to arrival at the hospital was 76.4 minutes for home games and 52.9
      minutes for away games. For air transport from another facility, the average time
      to arrival at the hospital was 37.4 minutes for home games and 24.0 minutes for
      away games. Air transportation utilization was increased in inter-facility
      transfers during home games (5/16, 31.3% vs. 4/20, 22.2%), and helicopters
      traveled a further distance (avg. 66.6 vs. 50.25 air miles). For patients coming
      from the scene during a home game, if the start of the game occurred after the
      trauma but before arrival to the trauma center, the average time of ground
      transport increased from 44.9 minutes to 120 minutes (p<0.0001). CONCLUSION: A
      mass gathering in close proximity to a rural trauma center does affect transport
      patterns and transport times for trauma patients. Further investigation is
      warranted in order to improve patient care during mass gathering events.

PMID- 29056782
TI  - The importance of mechano-electrical feedback and inertia in cardiac
      electromechanics.
AB  - In the past years, a number cardiac electromechanics models have been developed
      to better understand the excitation-contraction behavior of the heart. However,
      there is no agreement on whether inertial forces play a role in this system. In
      this study, we assess the influence of mass in electromechanical simulations,
      using a fully coupled finite element model. We include the effect of mechano
      electrical feedback via stretch activated currents. We compare five different
      models: electrophysiology, electromechanics, electromechanics with mechano
      electrical feedback, electromechanics with mass, and electromechanics with mass
      and mechano-electrical feedback. We simulate normal conduction to study
      conduction velocity and spiral waves to study fibrillation. During normal
      conduction, mass in conjunction with mechano-electrical feedback increased the
      conduction velocity by 8.12% in comparison to the plain electrophysiology case.
      During the generation of a spiral wave, mass and mechano-electrical feedback
      generated secondary wavefronts, which were not present in any other model. These
      secondary wavefronts were initiated in tensile stretch regions that induced
      electrical currents. We expect that this study will help the research community
      to better understand the importance of mechanoelectrical feedback and inertia in
      cardiac electromechanics.

PMID- 29056783
TI  - The Five-Factor Model of Personality and Physical Inactivity: A Meta-Analysis of
      16 Samples.
AB  - A sedentary lifestyle is harmful for health; personality traits may contribute to
      physical (in)activity. With participant-level data from 16 samples (N>125,000),
      we examined the personality correlates of physical inactivity, frequency of
      physical activity, and sedentary behavior (in a subset of samples). Lower
      Neuroticism and higher Conscientiousness were associated with more physical
      activity and less inactivity and sedentary behavior. Extraversion and Openness
      were also associated with more physical activity and less inactivity, but these
      traits were mostly unrelated to specific sedentary behaviors (e.g., TV watching).
      The results generally did not vary by age or sex. The findings support the notion
      that the interest, motivational, emotional, and interpersonal processes assessed
      by five-factor model traits partly shape the individual's engagement in physical
      activity.

PMID- 29056784
TI  - Theory and observations of upward field-aligned currents at the magnetopause
      boundary layer.
AB  - The dependence of the upward field-aligned current density (J||) at the dayside
      magnetopause boundary layer is well described by a simple analytic model based on
      a velocity shear generator. A previous observational survey confirmed that the
      scaling properties predicted by the analytical model are applicable between 11
      and 17 MLT. We utilize the analytic model to predict field-aligned currents using
      solar wind and ionospheric parameters and compare with direct observations. The
      calculated and observed parallel currents are in excellent agreement, suggesting
      that the model may be useful to infer boundary layer structures. However, near
      noon, where velocity shear is small, the kinetic pressure gradients and thermal
      currents, which are not included in the model, could make a small but significant
      contribution to J||. Excluding data from noon, our least squares fit returns
      log(J||,max_cal) = (0.96 +/- 0.04) log(J||_obs) + (0.03 +/- 0.01) where
      J||,max_cal = calculated J||,max and J||_obs = observed J||.

PMID- 29056785
TI  - Trading Youth for Citizenship? The Spousal Age Gap in Cross-Border Marriages.
AB  - Prior studies concerning patterns of intermarriage among immigrants have
      primarily focused on how factors such as race/ethnicity, educational attainment,
      and country of origin shape the choice of a spouse. Moreover, they have focused
      on intermarriage patterns among immigrants who are already in the US. Using the
      2010-2014 American Community Survey (ACS), we focus on immigrants who were not US
      citizens at the time of their marriage and highlight patterns of status exchange,
      specifically, the exchange of youth for citizenship. Towards this end, we compare
      the age gap between spouses across four different groups of respondents: 1) non
      citizens married to a citizen before or upon arrival to the US; 2) non-citizens
      married to a citizen after arrival to the US; 3) non-citizens married to a non
      citizen before or upon arrival to the US; and 4) non-citizens married to a non
      citizen after arrival in the US. We document the fact that a large fraction of
      marriages between citizens and non-citizens occurred before or upon arrival to
      the US. We also provide evidence that immigrants who migrate to the US after
      marrying a US citizen, particularly women, tend to be partnered with much older
      spouses, signaling an exchange of youth for citizenship.

PMID- 29056786
TI  - Impact of Ph.D. training: a comprehensive analysis based on a Japanese national
      doctoral survey.
AB  - Ph.D. training in academic labs offers the foundation for the production of
      knowledge workers, indispensable for the modern knowledge-based society.
      Nonetheless, our understanding on Ph.D. training has been insufficient due to
      limited access to the inside of academic labs. Furthermore, early careers of
      Ph.D. graduates are often difficult to follow, which makes the evaluation of
      training effects challenging. To address these limitations, this study aims to
      illustrate the settings of Ph.D. training in academic labs and examine their
      impact on several training outcomes, drawing on a national survey of a cohort of
      5000 Ph.D. graduates from Japanese universities. The result suggests that a
      supervising team structure as well as the frequency of supervision, contingent to
      a few contextual factors, determine the Ph.D. graduates' career decisions,
      performance, and degrees of satisfaction with the training programs.

PMID- 29056787
TI  - Scientometrics of peer review.
AB  - This article aims to introduce a special issue on "Scientometrics of peer
      review", which collects papers originally presented at workshops and conferences
      organised by the COST ACTION TD1306 "New frontiers of peer review". Peer review
      is the cornerstone of science and is one of the underlying processes that bring
      about publication traces that are at the heart of bibliometric studies.
      Unfortunately, despite its importance, quantitative studies on peer review are
      still poorly developed, often due to lack of data. The issue aims to promote the
      establishment of peer review as an interdisciplinary field of research and
      stimulate further quantitative research.

PMID- 29056788
TI  - The emergence of a field: a network analysis of research on peer review.
AB  - This article provides a quantitative analysis of peer review as an emerging field
      of research by revealing patterns and connections between authors, fields and
      journals from 1950 to 2016. By collecting all available sources from Web of
      Science, we built a dataset that included approximately 23,000 indexed records
      and reconstructed collaboration and citation networks over time. This allowed us
      to trace the emergence and evolution of this field of research by identifying
      relevant authors, publications and journals and revealing important development
      stages. Results showed that while the term "peer review" itself was relatively
      unknown before 1970 ("referee" was more frequently used), publications on peer
      review significantly grew especially after 1990. We found that the field was
      marked by three development stages: (1) before 1982, in which most influential
      studies were made by social scientists; (2) from 1983 to 2002, in which research
      was dominated by biomedical journals, and (3) from 2003 to 2016, in which
      specialised journals on science studies, such as Scientometrics, gained momentum
      frequently publishing research on peer review and so becoming the most
      influential outlets. The evolution of citation networks revealed a body of 47
      publications that form the main path of the field, i.e., cited sources in all the
      most influential publications. They could be viewed as the main corpus of
      knowledge for any newcomer in the field.

PMID- 29056789
TI  - Assessing peer review by gauging the fate of rejected manuscripts: the case of
      the Journal of Artificial Societies and Social Simulation.
AB  - This paper investigates the fate of manuscripts that were rejected from JASSS-The
      Journal of Artificial Societies and Social Simulation, the flagship journal of
      social simulation. We tracked 456 manuscripts that were rejected from 1997 to
      2011 and traced their subsequent publication as journal articles, conference
      papers or working papers. We compared the impact factor of the publishing journal
      and the citations of those manuscripts that were eventually published against the
      yearly impact factor of JASSS and the number of citations achieved by the JASSS
      mean and top cited articles. Only 10% of the rejected manuscripts were eventually
      published in a journal that was indexed in the Web of Science, although most of
      the rejected manuscripts were published elsewhere. Being exposed to more than one
      round of reviews before rejection, having received a more detailed reviewer
      report and being subjected to higher inter-reviewer disagreement were all
      associated with the number of citations received when the manuscript was
      eventually published. This indicates that peer review could contribute to
      increasing the quality even of rejected manuscripts.

PMID- 29056790
TI  - Post retraction citations in context: a case study.
AB  - This study examines the nature of citations to articles that were retracted in
      2014. Out of 987 retracted articles found in ScienceDirect, an Elsevier full text
      database, we selected all articles that received more than 10 citations between
      January 2015 and March 2016. Since the retraction year was known for only about
      83% of the retracted articles, we chose to concentrate on recent citations, that
      for certain appeared after the cited paper was retracted. Overall, we analyzed
      238 citing documents and identified the context of each citation as positive,
      negative or neutral. Our results show that the vast majority of citations to
      retracted articles are positive despite of the clear retraction notice on the
      publisher's platform and regardless of the reason for retraction. Positive
      citations can be also seen to articles that were retracted due to ethical
      misconduct, data fabrication and false reports. In light of these results, we
      listed some recommendations for publishers that could potentially minimize the
      referral to retracted studies as valid.

PMID- 29056791
TI  - Does single blind peer review hinder newcomers?
AB  - Several fields of research are characterized by the coexistence of two different
      peer review modes to select quality contributions for scientific venues, namely
      double blind (DBR) and single blind (SBR) peer review. In the first, the
      identities of both authors and reviewers are not known to each other, whereas in
      the latter the authors' identities are visible since the start of the review
      process. The need to adopt either one of these modes has been object of scholarly
      debate, which has mostly focused on issues of fairness. Past work reported that
      SBR is potentially associated with biases related to the gender, nationality, and
      language of the authors, as well as the prestige and type of their institutions.
      Nevertheless, evidence is lacking on whether revealing the identities of the
      authors favors reputed authors and hinder newcomers, a bias with potentially
      important consequences in terms of knowledge production. Accordingly, we
      investigate whether and to what extent SBR, compared to a DBR, relates to a
      higher ration of reputed scholars, at the expense of newcomers. This relation is
      pivotal for science, as past research provided evidence that newcomers support
      renovation and advances in a research field by introducing new and heterodox
      ideas and approaches, whereas inbreeding have serious detrimental effects on
      innovation and creativity. Our study explores the mentioned issues in the field
      of computer science, by exploiting a database that encompasses 21,535 research
      papers authored by 47,201 individuals and published in 71 among the 80 most
      impactful computer science conferences in 2014 and 2015. We found evidence that
      other characteristics of the conferences taken in consideration-SBR indeed
      relates to a lower ration of contributions from newcomers to the venue and
      particularly newcomers that are otherwise experienced of publishing in other
      computer science conferences, suggesting the possible existence of ingroup
      outgroup behaviors that may harm knowledge advancement in the long run.

PMID- 29056792
TI  - The miracle of peer review and development in science: an agent-based model.
AB  - It is not easy to rationalize how peer review, as the current grassroots of
      science, can work based on voluntary contributions of reviewers. There is no
      rationale to write impartial and thorough evaluations. If reviewers are
      unmotivated to carefully select high quality contributions, there is no risk in
      submitting low-quality work by authors. As a result, scientists face a social
      dilemma: if everyone acts according to his or her own self-interest, the outcome
      is low scientific quality. We examine how the increased relevance of public good
      benefits (journal impact factor), the editorial policy of handling incoming
      reviews, and the acceptance decisions that take into account reputational
      information, can help the evolution of high-quality contributions from authors.
      High effort from the side of reviewers is problematic even if authors cooperate:
      reviewers are still best off by producing low-quality reviews, which does not
      hinder scientific development, just adds random noise and unnecessary costs to
      it. We show with agent-based simulations why certain self-emerged current
      practices, such as the increased reliance on journal metrics and the reputation
      bias in acceptance, work efficiently for scientific development. Our results find
      no proper guidelines, however, how the system of voluntary peer review with
      impartial and thorough evaluations could be sustainable jointly with rapid
      scientific development.

PMID- 29056793
TI  - Quantifying the effect of editor-author relations on manuscript handling times.
AB  - In this article we study to what extent the academic peer review process is
      influenced by social relations between the authors of a manuscript and the editor
      handling the manuscript. Taking the open access journal PlosOne as a case study,
      our analysis is based on a data set of more than 100,000 articles published
      between 2007 and 2015. Using available data on handling editor, submission and
      acceptance time of manuscripts, we study the question whether co-authorship
      relations between authors and the handling editor affect the manuscript handling
      time, i.e. the time taken between the submission and acceptance of a manuscript.
      Our analysis reveals (1) that editors handle papers co-authored by previous
      collaborators significantly more often than expected at random, and (2) that such
      prior co-author relations are significantly related to faster manuscript
      handling. Addressing the question whether these shorter manuscript handling times
      can be explained by the quality of publications, we study the number of citations
      and downloads which accepted papers eventually accumulate. Moreover, we consider
      the influence of additional (social) factors, such as the editor's experience,
      the topical similarity between authors and editors, as well as reciprocal
      citation relations between authors and editors. Our findings show that, even when
      correcting for other factors like time, experience, and performance, prior co
      authorship relations have a large and significant influence on manuscript
      handling times, speeding up the editorial decision on average by 19 days.

PMID- 29056794
TI  - Duration and quality of the peer review process: the author's perspective.
AB  - To gain insight into the duration and quality of the scientific peer review
      process, we analyzed data from 3500 review experiences submitted by authors to
      the SciRev.sc website. Aspects studied are duration of the first review round,
      total review duration, immediate rejection time, the number, quality, and
      difficulty of referee reports, the time it takes authors to revise and resubmit
      their manuscript, and overall quality of the experience. We find clear
      differences in these aspects between scientific fields, with Medicine, Public
      health, and Natural sciences showing the shortest durations and Mathematics and
      Computer sciences, Social sciences, Economics and Business, and Humanities the
      longest. One-third of journals take more than 2 weeks for an immediate (desk)
      rejection and one sixth even more than 4 weeks. This suggests that besides the
      time reviewers take, inefficient editorial processes also play an important role.
      As might be expected, shorter peer review processes and those of accepted papers
      are rated more positively by authors. More surprising is that peer review
      processes in the fields linked to long processes are rated highest and those in
      the fields linked to short processes lowest. Hence authors' satisfaction is
      apparently influenced by their expectations regarding what is common in their
      field. Qualitative information provided by the authors indicates that editors can
      enhance author satisfaction by taking an independent position vis-a-vis reviewers
      and by communicating well with authors.

PMID- 29056795
TI  - Evaluating alternative systems of peer review: a large-scale agent-based
      modelling approach to scientific publication.
AB  - The debate on whether the peer-review system is in crisis has been heated
      recently. A variety of alternative systems have been proposed to improve the
      system and make it sustainable. However, we lack sufficient evidence and data
      related to these issues. Here we used a previously developed agent-based model of
      the scientific publication and peer-review system calibrated with empirical data
      to compare the efficiency of five alternative peer-review systems with the
      conventional system. We modelled two systems of immediate publication, with and
      without online reviews (crowdsourcing), a system with only one round of reviews
      and revisions allowed (re-review opt-out) and two review-sharing systems in which
      rejected manuscripts are resubmitted along with their past reviews to any other
      journal (portable) or to only those of the same publisher but of lower impact
      factor (cascade). The review-sharing systems outperformed or matched the
      performance of the conventional one in all peer-review efficiency, reviewer
      effort and scientific dissemination metrics we used. The systems especially
      showed a large decrease in total time of the peer-review process and total time
      devoted by reviewers to complete all reports in a year. The two systems with
      immediate publication released more scientific information than the conventional
      one but provided almost no other benefit. Re-review opt-out decreased the time
      reviewers devoted to peer review but had lower performance on screening papers
      that should not be published and relative increase in intrinsic quality of papers
      due to peer review than the conventional system. Sensitivity analyses showed
      consistent findings to those from our main simulations. We recommend prioritizing
      a system of review-sharing to create a sustainable scientific publication and
      peer-review system.

PMID- 29056796
TI  - Before The Philadelphia Negro: Residential Segregation in a Nineteenth-Century
      Northern City.
AB  - Although some scholars treat racial residential segregation in Northern cities as
      a twentieth-century phenomenon, recent research on New York and Chicago has shown
      that black-white segregation was already high and rising by 1880. We draw on data
      from the Philadelphia Social History Project and other new sources to study
      trends in this city as far back as 1850 and extending to 1900, a time when DuBois
      had completed his epic study of The Philadelphia Negro. Segregation of "free
      Negroes" in Philadelphia was high even before the Civil War but did not increase
      as the total and black populations grew through 1900. Geocoded information from
      the full-count data from the 1880 Census makes it possible to map the spatial
      configuration of black residents in fine detail. At the scale of the street
      segment, segregation in that year was extraordinarily high, reflecting a micro
      pattern in which many blacks lived in alleys and short streets. Although there
      was considerable class variation in the black community, higher status black
      households lived in areas that were little different in racial and class
      composition than lower status households.

PMID- 29056797
TI  - A Test for Anchoring and Yea-Saying in Experimental Consumption Data.
AB  - We analyze experimental survey data, with a random split into respondents who get
      an open-ended question on the amount of total family consumption (with follow-up
      unfolding brackets of the form "Is consumption $X or more?" for those who answer
      "don't know" or "refuse") and respondents who are immediately directed to
      unfolding brackets. In both cases, the entry point of the unfolding bracket
      sequence is randomized. Allowing for any type of selection into answering the
      open-ended or bracket questions, a nonparametric test is developed for errors in
      the answers to the first bracket question that are different from the usual
      reporting errors that will also affect open-ended answers. Two types of errors
      are considered explicitly: anchoring and yea-saying. Data are collected in the
      1995 wave of the Assets and Health Dynamics survey, which is representative of
      the population in the United States that is 70 years and older. We reject the
      joint hypothesis of no anchoring and no yea-saying. Once yea-saying is taken into
      account, we find no evidence of anchoring at the entry point.

PMID- 29056798
TI  - Bayesian Partition Models for Identifying Expression Quantitative Trait Loci.
AB  - Expression quantitative trait loci (eQTLs) are genomic locations associated with
      changes of expression levels of certain genes. By assaying gene expressions and
      genetic variations simultaneously on a genome-wide scale, scientists wish to
      discover genomic loci responsible for expression variations of a set of genes.
      The task can be viewed as a multivariate regression problem with variable
      selection on both responses (gene expression) and covariates (genetic
      variations), including also multi-way interactions among covariates. Instead of
      learning a predictive model of quantitative trait given combinations of genetic
      markers, we adopt an inverse modeling perspective to model the distribution of
      genetic markers conditional on gene expression traits. A particular strength of
      our method is its ability to detect interactive effects of genetic variations
      with high power even when their marginal effects are weak, addressing a key
      weakness of many existing eQTL mapping methods. Furthermore, we introduce a
      hierarchical model to capture the dependence structure among correlated genes.
      Through simulation studies and a real data example in yeast, we demonstrate how
      our Bayesian hierarchical partition model achieves a significantly improved power
      in detecting eQTLs compared to existing methods.

PMID- 29056799
TI  - Technological Response of Wild Macaques (Macaca fascicularis) to Anthropogenic
      Change.
AB  - Anthropogenic disturbances have a detrimental impact on the natural world; the
      vast expansion of palm oil monocultures is one of the most significant
      agricultural influences. Primates worldwide consequently have been affected by
      the loss of their natural ecosystems. Long-tailed macaques (Macaca fascilularis)
      in Southern Thailand have, however, learned to exploit oil palm nuts using stone
      tools. Using camera traps, we captured the stone tool behavior of one macaque
      group in Ao Phang-Nga National Park. Line transects placed throughout an
      abandoned oil palm plantation confirmed a high abundance of nut cracking sites.
      Long-tailed macaques previously have been observed using stone tools to harvest
      shellfish along the coasts of Thailand and Myanmar. The novel nut processing
      behavior indicates the successful transfer of existing lithic technology to a new
      food source. Such behavioral plasticity has been suggested to underlie cultural
      behavior in animals, suggesting that long-tailed macaques have potential to
      exhibit cultural tendencies. The use of tools to process oil palm nuts across
      multiple primate species allows direct comparisons between stone tool using
      nonhuman primates living in anthropogenic environments.

PMID- 29056800
TI  - Examining Cohort Effects in Developmental Trajectories of Substance Use.
AB  - The current study demonstrates the application of an analytic approach for
      incorporating multiple time trends in order to examine the impact of cohort
      effects on individual trajectories of eight drugs of abuse. Parallel analysis of
      two independent, longitudinal studies of high-risk youth that span ages 10 to 40
      across 23 birth cohorts between 1968 and 1991 was conducted. The two studies
      include the Michigan Longitudinal Study (current analytic sample of n=579 over 12
      cohorts between 1980-1991 and ages 10-27) and the Adolescent/Adult and Family
      Development Project (current analytic sample of n=849 over 11 cohorts between
      1968-1978 and ages 10-40). A series of nonlinear, multi-level growth models
      controlled simultaneously for cohort and age trends in substance use
      trajectories. Evidence was found for both age and cohort effects across most
      outcomes as well as several significant age-by-cohort interactions. Findings
      suggest cohort trends in developmental trajectories of substance use are sample
      and drug-specific in the adolescent and early to mid-adult years. Thus, studies
      that do not control for both trends may confound cohort and developmental trends
      in substance use. For this reason, demonstration of one analytic approach that
      can be used to examine both time trends simultaneously is informative for future
      multi-cohort longitudinal studies where change over time is of interest.

PMID- 29056802
TI  - Data Shared Lasso: A Novel Tool to Discover Uplift.
AB  - A model is presented for the supervised learning problem where the observations
      come from a fixed number of pre-specified groups, and the regression coefficients
      may vary sparsely between groups. The model spans the continuum between
      individual models for each group and one model for all groups. The resulting
      algorithm is designed with a high dimensional framework in mind. The approach is
      applied to a sentiment analysis dataset to show its efficacy and
      interpretability. One particularly useful application is for finding sub
      populations in a randomized trial for which an intervention (treatment) is
      beneficial, often called the uplift problem. Some new concepts are introduced
      that are useful for uplift analysis. The value is demonstrated in an application
      to a real world credit card promotion dataset. In this example, although sending
      the promotion has a very small average effect, by targeting a particular subgroup
      with the promotion one can obtain a 15% increase in the proportion of people who
      purchase the new credit card.

PMID- 29056801
TI  - Life Course Changes in Smoking by Gender and Education: A Cohort Comparison
      Across France and the United States.
AB  - Widening of educational disparities and a narrowing female advantage in mortality
      stem in good part from disparities in smoking. The changes in smoking and
      mortality disparities across cohorts and countries have been explained by an
      epidemic model of cigarette use but are also related to life course changes. To
      better describe and understand changing disparities over the life course, we
      compare age patterns of smoking in three cohorts and two nations (France and the
      United States) using smoking history measures from the 2010 French Health
      Barometer (N = 20,940) and the 2010 U.S. National Health Interview Survey Sample
      Adult File (N = 20,444). The results demonstrate statistically significant
      widening of gender and educational differences from adolescence to early and
      middle adulthood, thus accentuating the disparities already emerging during
      adolescence. In addition, the widening disparities over the life course have been
      changing across cohorts: Age differences in educational disparities have grown in
      recent cohorts (especially in France), while age differences in gender
      disparities have narrowed. The findings highlight the multiple sources of
      inequality in smoking and health in high-income nations.

PMID- 29056803
TI  - Homelessness and Aging Out of Foster Care: A National Comparison of Child Welfare
      Involved Adolescents.
AB  - The present study represents the first large-scale, prospective comparison to
      test whether aging out of foster care contributes to homelessness risk in
      emerging adulthood. A nationally representative sample of adolescents
      investigated by the child welfare system in 2008 to 2009 from the second cohort
      of the National Survey of Child and Adolescent Well-being Study (NSCAW II)
      reported experiences of housing problems at 18- and 36-month follow-ups. Latent
      class analyses identified subtypes of housing problems, including literal
      homelessness, housing instability, and stable housing. Regressions predicted
      subgroup membership based on aging out experiences, receipt of foster care
      services, and youth and county characteristics. Youth who reunified after out-of
      home placement in adolescence exhibited the lowest probability of literal
      homelessness, while youth who aged out experienced similar rates of literal
      homelessness as youth investigated by child welfare but never placed out of home.
      No differences existed between groups on prevalence of unstable housing. Exposure
      to independent living services and extended foster care did not relate with
      homelessness prevention. Findings emphasize the developmental importance of
      families in promoting housing stability in the transition to adulthood, while
      questioning child welfare current focus on preparing foster youth to live.

PMID- 29056804
TI  - Gender Differences in Emotion Expression in Low-Income Adolescents Under Stress.
AB  - Gender roles in mainstream U.S. culture suggest that girls express more
      happiness, sadness, anxiety, and shame/embarrassment than boys, while boys
      express more anger and externalizing emotions, such as contempt. However, gender
      roles and emotion expression may be different in low-income and ethnically
      diverse families, as children and parents are often faced with greater
      environmental stressors and may have different gender expectations. This study
      examined gender differences in emotion expression in low-income adolescents, an
      understudied population. One hundred and seventy nine adolescents (aged 14-17)
      participated in the Trier Social Stress Test (TSST). Trained coders rated
      adolescents' expressions of happiness, sadness, anxiety, shame/embarrassment,
      anger, and contempt during the TSST using a micro-analytic coding system.
      Analyses showed that, consistent with gender roles, girls expressed higher levels
      of happiness and shame than boys; however, contrary to traditional gender roles,
      girls showed higher levels of contempt than boys. Also, in contrast to cultural
      stereotypes, there were no differences in anger between boys and girls. Findings
      suggest gender-role inconsistent displays of externalizing emotions in low-income
      adolescents under acute stress, and may reflect different emotion socialization
      experiences in this group.

PMID- 29056805
TI  - The Conditional Indirect Effects of Suicide Attempt History and Psychiatric
      Symptoms on the Association Between Intimate Partner Violence and Suicide
      Ideation.
AB  - BACKGROUND: Women seeking shelter from intimate partner violence (IPV) experience
      heightened risk for suicide ideation and attempts compared to abused and non
      abused women in the general population. However, few theory-guided studies have
      examined what cognitive-emotional symptoms might underlie this increased risk.
      METHODS: Guided by fluid vulnerability theory, this cross-sectional, survey study
      tested whether depressive symptoms, PTSD symptoms, and hopelessness mediate the
      association between IPV (coercive control and physical violence) and suicide
      ideation and whether suicide attempt history facilitated these mediated relations
      in 134 women seeking shelter from IPV. RESULTS: Depressive symptoms, but not PTSD
      symptoms or hopelessness, mediated the relation between coercive control and
      suicide ideation, and suicide attempt history facilitated this association. No
      variables mediated the association between physical violence and suicide
      ideation. LIMITATIONS: The small sample size may have limited statistical power.
      The cross-sectional design precludes temporal conclusions from being drawn.
      CONCLUSIONS: Shelter-seeking women subjected to coercive control who experience
      associated depressive symptoms may be at risk of suicide ideation, with history
      of a suicide attempt increasing this risk. Fluid vulnerability theory may help
      guide suicide risk assessment and intervention efforts among women seeking
      shelter from IPV.

PMID- 29056806
TI  - Timing of Sexual Initiation and Relationship Satisfaction in Young Adult Marital
      and Cohabiting Unions.
AB  - Using the National Longitudinal Study of Adolescent to Adult Health, this
      research examines the association between timing of oral sex initiation and
      marital and cohabiting relationship satisfaction among young adults. Findings
      indicate that women who transition to oral sex "late" or who have no oral sex
      experience report higher levels of relationship satisfaction in their current
      coresidential unions than do women who transition at a "normative" age. Higher
      levels of relationship satisfaction among women who transition "late," however,
      appear to be explained by their lower likelihood of experiencing forced sexual
      relations and sexually transmitted infections. We find no evidence of any
      association between timing of oral sex initiation and relationship satisfaction
      among men. To best promote healthy relationships, researchers, practitioners, and
      educators need to better understand the various types of sexual activities in
      which young people engage.

PMID- 29056807
TI  - Depressive symptoms, friend distress, and self-blame: Risk factors for adolescent
      peer victimization.
AB  - Past research indicates that depressed adolescents experience increased risk for
      peer victimization. Less is known about the conditions under which depressive
      symptoms predict social vulnerability and the mechanism underlying such links.
      The current study considers a) characterological self-blaming attributions as a
      social cognitive mechanism accounting for links between depressive symptoms and
      victimization across the first two years of middle school and b) the potential
      moderating role of friends' level of depressive symptoms. Relying on an
      ethnically diverse sample of 5,374 adolescents, multilevel moderated mediation
      analyses indicated that maladaptive attributions accounted for links between 6th
      grade depressive symptoms and increases in 7th grade victimization. Moreover,
      this mediational pathway was strongest for students whose friends also
      experienced heightened depressive symptoms at the beginning of middle school.
      These results highlight the roles of both intra- and inter-personal risk factors
      in predicting social cognitive biases and future victimization risk during the
      middle school years.

PMID- 29056808
TI  - Family Planning and Deforestation: Evidence from the Ecuadorian Amazon.
AB  - Despite an abundant body of literature exploring the relationship between
      population growth and forest cover change, comparatively little research has
      explored the forest cover impacts of family planning use, which is a key
      determinant of the rate of population growth in many developing country contexts.
      Using data from a farm-level panel survey in the Northern Ecuadorian Amazon, this
      paper addresses whether family planning use impacts forest cover change.
      Longitudinal model results show that after controlling for household life cycle
      and land use variables, family planning use did not have an independent effect on
      deforestation, reforestation, or net forest loss between 1990 and 2008. Forest
      cover change patterns appear indicative of farm life cycle effects. However,
      family planning use is associated with reduced subsequent fertility among
      households, suggesting that the relationship between population growth from
      births and forest cover change may be limited in this setting.

PMID- 29056809
TI  - On neutron activation analysis with gammagamma coincidence spectrometry.
AB  - A new gammagamma coincidence system has been set up at NIST. It is operated with
      a digital data finder supported by new software developed at NIST. The system is
      used to explore possible enhancements in instrumental neutron activation analysis
      (INAA) and study applicability to neutron capture prompt gamma activation
      analysis (PGAA). The performance of the system is tested with certified reference
      materials for efficiency calibration and quantitative performance. Comparisons of
      INAA results based on conventional gamma-ray spectrometry data with INAA results
      based on coincidence data obtained from the same samples show improvements in the
      counting uncertainties and demonstrates the quantitative accuracy of the new
      system.

PMID- 29056810
TI  - Connected speech in transient aphasias after left hemisphere resective surgery.
AB  - BACKGROUND: Transient aphasias are common in the first few days after resective
      surgery to the language-dominant hemisphere. The specific speech and language
      deficits that occur are related to the location of the surgical site, and may
      include impairments in fluency, lexical access, repetition, and comprehension.
      The impact of these transient aphasias on connected speech production has not
      previously been investigated. AIMS: The goals of this study were to characterize
      the nature of connected speech deficits in the immediate post-surgical period,
      and to determine which deficits resolve completely within 1 month. METHODS &
      PROCEDURES: Forty-three patients undergoing resective surgery in the left
      (language-dominant) hemisphere participated in the study. Brief connected speech
      samples were obtained before surgery, and at 2-3 days post-surgery. In a subset
      of 24 patients (all of whom presented with aphasia in the immediate post-surgical
      period), follow-up samples were also obtained at 1 month post-surgery. The
      samples were transcribed and coded in CHAT format. Ten connected speech measures
      were derived from each speech sample, and were then compared by time point.
      OUTCOMES & RESULTS: At 2-3 days post surgery, deficits were observed in all 10
      connected speech measures in comparison to pre-surgical samples: there were
      decreases in words per minute, words per utterance, and the use of embedded
      clauses, and increases in phonological errors, lexical access difficulties,
      morphosyntactic errors, filled pauses, false starts and retraced sequences. The
      proportion of closed class words could be perturbed in either direction. At 1
      month post-surgery, 8 of the 10 connected speech measures had significantly
      improved, and all measures reflecting structural features (words per utterance,
      number of embeddings, morphosyntactic errors, proportion of words that were
      closed class) were equivalent to the pre-surgical time point. Subtle deficits
      persisted in some other measures; in particular, there were more phonological
      errors and lexical access difficulties than at the pre-surgical point.
      CONCLUSIONS: Transient aphasias after left hemisphere surgery impacted all
      aspects of connected speech in the immediate post-surgical period. Most of these
      deficits were largely or completely resolved by 1 month post surgery, but some
      subtle impairments persisted.

PMID- 29056811
TI  - Multi-modal anatomical Optical Coherence Tomography and CT for in vivo Dynamic
      Upper Airway Imaging.
AB  - We describe a novel, multi-modal imaging protocol for validating quantitative
      dynamic airway imaging performed using anatomical Optical Coherence Tomography
      (aOCT). The aOCT system consists of a catheter-based aOCT probe that is deployed
      via a bronchoscope, while a programmable ventilator is used to control airway
      pressure. This setup is employed on the bed of a Siemens Biograph CT system
      capable of performing respiratory-gated acquisitions. In this arrangement the
      position of the aOCT catheter may be visualized with CT to aid in co
      registration. Utilizing this setup we investigate multiple respiratory pressure
      parameters with aOCT, and respiratory-gated CT, on both ex vivo porcine trachea
      and live, anesthetized pigs. This acquisition protocol has enabled real-time
      measurement of airway deformation with simultaneous measurement of pressure under
      physiologically relevant static and dynamic conditions- inspiratory peak or peak
      positive airway pressures of 10-40 cm H2O, and 20-30 breaths per minute for
      dynamic studies. We subsequently compare the airway cross sectional areas (CSA)
      obtained from aOCT and CT, including the change in CSA at different stages of the
      breathing cycle for dynamic studies, and the CSA at different peak positive
      airway pressures for static studies. This approach has allowed us to improve our
      acquisition methodology and to validate aOCT measurements of the dynamic airway
      for the first time. We believe that this protocol will prove invaluable for aOCT
      system development and greatly facilitate translation of OCT systems for airway
      imaging into the clinical setting.

PMID- 29056812
TI  - Instrument to detect syncope and the onset of shock.
AB  - Currently the diagnosis of hemorrhagic shock is essentially clinical, relying on
      the expertise of nurses and doctors. One of the first measurable physiological
      changes that marks the onset of hemorrhagic shock is a decrease in capillary
      blood flow. Diffuse correlation spectroscopy (DCS) quantifies this decrease. DCS
      collects and analyzes multiply scattered, coherent, near infrared light to assess
      relative blood flow. This work presents a preliminary study using a DCS
      instrument with human subjects undergoing a lower body negative pressure (LBNP)
      protocol. This work builds on previous successful DCS instrumentation development
      and we believe it represents progress toward understanding how DCS can be used in
      a clinical setting.

PMID- 29056814
TI  - Level of structural quality and process quality in rural preschool classrooms.
AB  - Preschool classrooms with varying levels of structural quality requirements
      across the state of West Virginia were investigated for differences in measured
      structural and process quality. Quality was measured using group size, child-to
      teacher/staff ratio, teacher education, and the Early Childhood Environmental
      Rating Scale-Revised (ECERS-R; Harms, T., Clifford, R. M., & Cryer, D. (2005).
      The early childhood environment rating scale-revised. New York, NY: Teachers
      College Press). Thirty-six classrooms with less structural quality requirements
      and 136 with more structural quality requirements were measured. There were
      significant differences between classroom type, with classrooms with more
      structural quality requirements having significantly higher teacher education
      levels and higher environmental rating scores on the ECERS-R subscales of Space
      and Furnishings, Activities, and Program Structure. Results support previous
      research that stricter structural state regulations are correlated with higher
      measured structural and process quality in preschool classrooms. Implications for
      preschool state quality standards are discussed.

PMID- 29056813
TI  - A disposable, flexible skin patch for clinical optical perfusion monitoring at
      multiple depths.
AB  - Stable, relative localization of source and detection fibers is necessary for
      clinical implementation of quantitative optical perfusion monitoring methods such
      as diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy
      (DRS). A flexible and compact device design is presented as a platform for
      simultaneous monitoring of perfusion at a range of depths, enabled by precise
      location of optical fibers in a robust and secure adhesive patch. We will discuss
      preliminary data collected on human subjects in a lower body negative pressure
      model for hypovolemic shock. These data indicate that this method facilitates
      simple and stable simultaneous monitoring of perfusion at multiple depths and
      within multiple physiological compartments.

PMID- 29056815
TI  - The Educational Gradient in Health in China.
AB  - It has been well established that better educated individuals enjoy better health
      and longevity. In theory, the educational gradients in health could be flattening
      if diminishing returns to improved average education levels and the influence of
      earlier population health interventions outweigh the gradient-steepening effects
      of new medical and health technologies. This paper documents how the gradients
      are evolving in China, a rapidly developing country, about which little is known
      on this topic. Based on recent mortality data and nationally representative
      health surveys, we find large and, in some cases, steepening educational
      gradients. We also find that the gradients vary by cohort, gender and region.
      Further, we find that the gradients can only partially be accounted for by
      economic factors. These patterns highlight the double disadvantage of those with
      low education, and suggest the importance of policy interventions that foster
      both aspects of human capital for them.

PMID- 29056817
TI  - Estimating treatment effects in observational studies with both prevalent and
      incident cohorts.
AB  - Registry databases are increasingly being used for comparative effectiveness
      research in cancer. Such databases reflect the real-world patient population and
      physician practice, and thus are natural sources for comparing multiple treatment
      scenarios and the associated long-term clinical outcomes. Registry databases
      usually include both incident and prevalent cohorts, which provide valuable
      complementary information for patients with more recent diagnoses in the incident
      cohort as well as patients with long-term follow-up data in the prevalent cohort.
      However, utilizing such data to derive valid inference poses two major
      challenges: the data from a prevalent cohort are not random samples of the target
      population, and there may be substantial differences in the baseline
      characteristics of patients between treatment arms, which influences the
      decisions about treatment selection in both cohorts. In this article, we extend
      propensity score methodology to observational studies that involve both prevalent
      and incident cohorts, and assess the effectiveness of radiation therapy in SEER
      Medicare patients diagnosed with stage IV breast cancer. Specifically, we utilize
      the incident cohort to estimate the propensity for receiving radiation therapy,
      and then combine data from both the incident and prevalent cohorts to estimate
      the effect of radiation therapy by adjusting for the propensity scores in the
      model. We evaluate the proposed method with simulations. We demonstrate that the
      proposed propensity score method simultaneously removes sampling bias and
      selection bias under several assumptions.

PMID- 29056816
TI  - The spatial spread of schistosomiasis: A multidimensional network model applied
      to Saint-Louis region, Senegal.
AB  - Schistosomiasis is a parasitic, water-related disease that is prevalent in
      tropical and subtropical areas of the world, causing severe and chronic
      consequences especially among children. Here we study the spatial spread of this
      disease within a network of connected villages in the endemic region of the Lower
      Basin of the Senegal River, in Senegal. The analysis is performed by means of a
      spatially explicit metapopulation model that couples local-scale eco
      epidemiological dynamics with spatial mechanisms related to human mobility
      (estimated from anonymized mobile phone records), snail dispersal and
      hydrological transport of schistosome larvae along the main water bodies of the
      region. Results show that the model produces epidemiological patterns consistent
      with field observations, and point out the key role of spatial connectivity on
      the spread of the disease. These findings underline the importance of considering
      different transport pathways in order to elaborate disease control strategies
      that can be effective within a network of connected populations.

PMID- 29056818
TI  - Analysis of Censored Longitudinal Data with Skewness and a Terminal Event.
AB  - In HIV/AIDS study, the measurements viral load are often highly skewed and left
      censored because of a lower detection limit. Furthermore, a terminal event (e.g.,
      death) stops the follow-up process. The time to terminal event may be dependent
      on the viral load measurements. In this article, we present a joint analysis
      framework to model the censored longitudinal data with skewness and a terminal
      event process. The estimation is carried out by adaptive Gaussian quadrature
      techniques in SAS procedure NLMIXED. The proposed model is evaluated by a
      simulation study and is applied to the motivating Multicenter AIDS Cohort Study
      (MACS).

PMID- 29056819
TI  - Does Pathway into 12-Step Programs Influence 12-Step-Related Benefit?
AB  - Most 12-step research recruits participants who are seeking treatment (cf.
      Kaskutas, Turk, Bond, & Weisner, 2003; Robinson, Cranford, Webb, & Brower, 2007),
      leaving open the question of how non-treatment-seeking individuals respond to 12
      step involvement. The current study examined whether participants recruited from
      community-based Alcoholics Anonymous (AA) clubs or via advertisement/word-of
      mouth differed in their 12-step attendance rates, substance use, and the
      association between these constructs compared to participants recruited from
      substance abuse treatment. Multilevel analyses showed that while associations
      between 12-step attendance and improved substance use did not differ by
      recruitment group, participants recruited from community-based AA clubs had
      higher 12-step attendance rates and a higher proportion of alcohol abstinent days
      than did all other participants. Results indicate that using diverse recruitment
      strategies may be necessary to obtain samples that are representative of the
      actual population of 12-step affiliates and to achieve results that estimate the
      true magnitude of 12-step effects.

PMID- 29056820
TI  - Differentiation of Writing and Drawing by U.S. Two- to Five-Year-Olds.
AB  - To investigate preschoolers' knowledge about symbol systems, we compared the
      written and drawn productions of 2-5-year-old U.S. children. In Study 1, children
      (N = 88) wrote and drew four targets, including their own name and a picture of
      themselves. Children differentiated writings from drawings in the implements they
      used, the size of their productions, and use of recognizable letters. Some
      distinctions were present in the youngest children and others became more
      prominent with age. In Study 2, adults (N = 16) who judged whether the
      productions were writings or drawings performed above the level of chance for all
      age groups. Adults did better for children's names and self-portraits than for
      other targets, suggesting that the name plays a leading role in U.S. children's
      learning about writing. Overall, the results show that children begin to learn
      about formal differences between writing and drawing at an early age.

PMID- 29056822
TI  - THE ECONOMIC AND CAREER EFFECTS OF SEXUAL HARASSMENT ON WORKING WOMEN.
AB  - Many working women will experience sexual harassment at some point in their
      careers. While some report this harassment, many leave their jobs to escape the
      harassing environment. This mixed-methods study examines whether sexual
      harassment and subsequent career disruption affect women's careers. Using in
      depth interviews and longitudinal survey data from the Youth Development Study,
      we examine the effect of sexual harassment for women in the early career. We find
      that sexual harassment increases financial stress, largely by precipitating job
      change, and can significantly alter women's career attainment.

PMID- 29056821
TI  - Engineering Novel and Improved Biocatalysts by Cell Surface Display.
AB  - Biocatalysts, especially enzymes, have the ability to catalyze reactions with
      high product selectivity, utilize a broad range of substrates, and maintain
      activity at low temperature and pressure. Therefore, they represent a renewable,
      environmentally friendly alternative to conventional catalysts. Most current
      industrial-scale chemical production processes using biocatalysts employ soluble
      enzymes or whole cells expressing intracellular enzymes. Cell surface display
      systems differ by presenting heterologous enzymes extracellularly, overcoming
      some of the limitations associated with enzyme purification and substrate
      transport. Additionally, coupled with directed evolution, cell surface display is
      a powerful platform for engineering enzymes with enhanced properties. In this
      review, we will introduce the molecular and cellular principles of cell surface
      display and discuss how it has been applied to engineer enzymes with improved
      properties as well as to develop surface-engineered microbes as whole-cell
      biocatalysts.

PMID- 29056823
TI  - Differential relationships between language skills and working memory in Turkish
      Dutch and native-Dutch first-graders from low-income families.
AB  - In the Netherlands, Turkish-Dutch children constitute a substantial group of
      children who learn to speak Dutch at the age of four after they learned to speak
      Turkish. These children are generally academically less successful. Academic
      success appears to be affected by both language proficiency and working memory
      skill. The goal of this study was to investigate the relationship between
      language skills and working memory in Turkish-Dutch and native-Dutch children
      from low-income families. The findings revealed reduced Dutch language and Dutch
      working-memory skills for Turkish-Dutch children compared to native-Dutch
      children. Working memory in native-Dutch children was unrelated to their language
      skills, whereas in Turkish-Dutch children strong correlations were found both
      between Turkish language skills and Turkish working-memory performance and
      between Dutch language skills and Dutch working-memory performance. Reduced
      language proficiencies and reduced working-memory skills appear to manifest
      itself in strong relationships between working memory and language skills in
      Turkish-Dutch children. The findings seem to indicate that limited verbal working
      memory and language deficiencies in bilingual children may have reciprocal
      effects that strongly warrants adequate language education.

PMID- 29056824
TI  - Determination of temperature dependence of full matrix material constants of PZT
      8 piezoceramics using only one sample.
AB  - Resonant ultrasound spectroscopy (RUS) was used to determine the temperature
      dependence of full matrix material constants of PZT-8 piezoceramics from room
      temperature to 100  degrees C. Property variations from sample to samples can be
      eliminated by using only one sample, so that data self-consistency can be
      guaranteed. The RUS measurement system error was estimated to be lower than
      2.35%. The obtained full matrix material constants at different temperatures all
      have excellent self-consistency, which can help accurately predict device
      performance at high temperatures using finite element simulations.

PMID- 29056826
TI  - Ultra-Sensitive Lab-on-a-Chip Detection of Sudan I in Food using Plasmonics
      Enhanced Diatomaceous Thin Film.
AB  - Sudan I is a carcinogenic compound containing an azo group that has been
      illegally utilized as an adulterant in food products to impart a bright red color
      to foods. In this paper, we develop a facile lab-on-a-chip device for instant,
      ultra-sensitive detection of Sudan I from real food samples using plasmonics
      enhanced diatomaceous thin film, which can simultaneously perform on-chip
      separation using thin layer chromatography (TLC) and highly specific sensing
      using surface-enhanced Raman scattering (SERS) spectroscopy. Diatomite is a kind
      of nature-created photonic crystal biosilica with periodic pores and was used
      both as the stationary phase of the TLC plate and photonic crystals to enhance
      the SERS sensitivity. The on-chip chromatography capability of the TLC plate was
      verified by isolating Sudan I in a mixture solution containing Rhodamine 6G,
      while SERS sensing was achieved by spraying gold colloidal nanoparticles into the
      sensing spot. Such plasmonics-enhanced diatomaceous film can effectively detect
      Sudan I with more than 10 times improvement of the Raman signal intensity than
      commercial silica gel TLC plates. We applied this lab-on-a-chip device for real
      food samples and successfully detected Sudan I in chili sauce and chili oil down
      to 1 ppm, or 0.5 ng/spot. This on-chip TLC-SERS biosensor based on diatomite
      biosilica can function as a cost-effective, ultra-sensitive, and reliable
      technology for screening Sudan I and many other illicit ingredients to enhance
      food safety.

PMID- 29056825
TI  - Central Poststroke Pain: Its Profile among Stroke Survivors in Kano, Nigeria.
AB  - BACKGROUND: Central poststroke pain (CPSP) caused by sensory dysfunction of
      central origin is a disabling condition that significantly affects the quality of
      life of stroke patients. AIM: The aim of this study is to determine the clinical
      profiles and pattern of CPSP among stroke patients in Kano, Nigeria. METHODS: The
      study was a cross-sectional design involving stroke survivors who were >=18 years
      old and with no significant cognitive impairment approved by the Research Ethics
      Committee of Aminu Kano Teaching Hospital. Participants were assessed using
      diagnostic criteria form, the douleur neuropathique 4 questions (DN4
      questionnaire), and Leeds assessment of neuropathic symptoms and signs (LANNS).
      RESULTS: A total of 120 stroke patients participated in the study, in which 6
      (5%) were diagnosed with CPSP occurring within the first 3 months in 50% of the
      participants. The pain characteristics were mainly moderate (83.3%), burning
      (62.5%), and continuously experienced (66.7%). The frequently affected parts were
      extremities or occurring as hemisyndrome. CONCLUSION: Prevalence of CPSP
      following stroke is low. The clinical features are variable and can occur at a
      varied time and different intensities and locations. However, it majorly occurs
      within the first few months post stroke.

PMID- 29056827
TI  - Linking regional stakeholder scenarios and shared socioeconomic pathways:
      Quantified West African food and climate futures in a global context.
AB  - The climate change research community's shared socioeconomic pathways (SSPs) are
      a set of alternative global development scenarios focused on mitigation of and
      adaptation to climate change. To use these scenarios as a global context that is
      relevant for policy guidance at regional and national levels, they have to be
      connected to an exploration of drivers and challenges informed by regional
      expertise. In this paper, we present scenarios for West Africa developed by
      regional stakeholders and quantified using two global economic models, GLOBIOM
      and IMPACT, in interaction with stakeholder-generated narratives and scenario
      trends and SSP assumptions. We present this process as an example of linking
      comparable scenarios across levels to increase coherence with global contexts,
      while presenting insights about the future of agriculture and food security under
      a range of future drivers including climate change. In these scenarios, strong
      economic development increases food security and agricultural development. The
      latter increases crop and livestock productivity leading to an expansion of
      agricultural area within the region while reducing the land expansion burden
      elsewhere. In the context of a global economy, West Africa remains a large
      consumer and producer of a selection of commodities. However, the growth in
      population coupled with rising incomes leads to increases in the region's
      imports. For West Africa, climate change is projected to have negative effects on
      both crop yields and grassland productivity, and a lack of investment may
      exacerbate these effects. Linking multi-stakeholder regional scenarios to the
      global SSPs ensures scenarios that are regionally appropriate and useful for
      policy development as evidenced in the case study, while allowing for a critical
      link to global contexts.

PMID- 29056831
TI  - Reducing the uncertainty induced by spatial aggregation in accessibility and
      spatial interaction applications.
AB  - Analyses of spatial interaction are to some degree plagued by uncertainty
      regarding the impact of spatially dispersed interaction masses within zones on
      travel times. In this paper, interaction-weighted travel times are computed from
      a matrix between regularly distributed points at fine resolution, and used
      together with secondary data to improve estimates of interaction weighted travel
      time based on commonly applied methods. The paper proposes a method for computing
      intra-zonal, interaction weighted travel times that is considerably less
      sensitive to spatial aggregation than existing approaches, and demonstrates that
      population-weighted centroids are to be preferred over geographically-weighted
      centroids.

PMID- 29056829
TI  - Low Circulating TRAIL Levels Are Associated with Increase of Resistin and
      Lipocalin-2/ngal Adipokines in Postmenopausal Women.
AB  - OBJECTIVE: Tumor necrosis factor- (TNF-) related apoptosis-inducing ligand
      (TRAIL) is attracting attention for its role in the physiopathology of metabolic
      disease/diabetes. Evidence suggests that it might protect against metabolic
      abnormalities driven by obesity-induced dysregulated secretion of adipokines, but
      this role of TRAIL has not yet been fully established. On this basis, we aimed to
      investigate the potential association between TRAIL and adipokine levels in a
      cohort of subjects in which age/gender/hormonal interferences were excluded.
      METHODS: Serum levels of TRAIL and a panel of adipokines were measured in
      postmenopausal women (n = 147) stratified according to waist circumference
      measures as normal, overweight, or obese. The panel of adipokines included
      interleukin- (IL-) 6, IL-8, IL-1beta, adipsin, lipocalin-2/neutrophil gelatinase
      associated lipocalin (ngal), TNF-alpha, monocyte chemoattractant protein-1,
      plasminogen activator inhibitor-1, hepatocyte growth factor, resistin, leptin,
      adiponectin, and nerve growth factor. RESULTS: Low serum TRAIL concentration
      (deciles I-IV) was significantly and inversely correlated with resistin and
      lipocalin 2/ngal levels (r = -0.502 and p < 0.001 and r = -0.360 and p < 0.01,
      resp.). Both associations retained their statistical significance after
      adjustment for confounding factors, such as waist circumference and age.
      CONCLUSIONS: Our data indicate a link between low circulating levels of TRAIL and
      markers of obesity-induced diseases (resistin and lipocalin-2/ngal), highlighting
      a new potential axis of TRAIL functions.

PMID- 29056830
TI  - Aloperine Protects Mice against DSS-Induced Colitis by PP2A-Mediated
      PI3K/Akt/mTOR Signaling Suppression.
AB  - Colitis is a major form of inflammatory bowel disease which involved mucosal
      immune dysfunction. Aloperine is an alkaloid isolated from the shrub Sophora
      alopecuroides L. and has been recognized as an effective treatment for
      inflammatory and allergic diseases. The present study aimed to examine the
      molecular mechanisms underlying aloperine-mediated colitis protection. We found
      that aloperine treatment improved colitis induced by dextran sodium sulfate (DSS)
      based on body weight, disease activity index, colonic length, and spleen index.
      Aloperine also effectively attenuated DSS-induced intestinal inflammation based
      on the pathological score and myeloperoxidase expression and activity in colon
      tissues. In addition, aloperine regulated T-cell proportions and promoted Foxp3
      expression in the spleens and mesenteric lymph nodes of DSS-induced colitis mice
      and in the spleens of the Foxp3GFP mice. Aloperine inhibited Jurkat and mouse
      naive T-cell apoptosis. Furthermore, aloperine inhibited PI3K/Akt/mTOR signaling
      and upregulated PP2A expression in the DSS-induced colitis mice and in Jurkat
      cells, but LB-100 (PP2A inhibitor) resulted in an elevated Akt activity in Jurkat
      cells, activated T-cells, and human splenic mononuclear cells. Aloperine
      inhibited T-cell and lymphocyte proliferation, but LB-100 reverse these effects.
      In conclusion, aloperine regulates inflammatory responses in colitis by
      inhibiting the PI3K/Akt/mTOR signaling in a PP2A-dependent manner.

PMID- 29056832
TI  - Population growth, accessibility spillovers and persistent borders: Historical
      growth in West-European municipalities.
AB  - Lack of cross-border transport supply has repeatedly been blamed for the fact
      that national borders limit spatial interaction and, consequently, the growth of
      border regions. This study applies an accessibility approach to investigate for
      most municipalities in ten countries in mainland West Europe if foreign transport
      supply is lagging behind, and if population growth in these municipalities has
      been affected by the limits that national borders have imposed on market access.
      To do so, data describing historical population changes and road networks between
      1961 and 2011 have been used. The results show that in the study area, cross
      border transport accessibility was not at a disadvantage in 1961 and has since
      then grown even more than domestic accessibility. However, municipal population
      growth has depended almost exclusively on domestic market access. Processes of
      economic international integration in the study area are found to coincide with
      the growth of cross-border accessibility, but do not have a clear coincidence
      with the effects of cross-border accessibility on population growth.

PMID- 29056828
TI  - Acid-Sensing Ion Channels as Potential Therapeutic Targets in Neurodegeneration
      and Neuroinflammation.
AB  - Acid-sensing ion channels (ASICs) are a family of proton-sensing channels that
      are voltage insensitive, cation selective (mostly permeable to Na+), and
      nonspecifically blocked by amiloride. Derived from 5 genes (ACCN1-5), 7 subunits
      have been identified, 1a, 1b, 2a, 2b, 3, 4, and 5, that are widely expressed in
      the peripheral and central nervous system as well as other tissues. Over the
      years, different studies have shown that activation of these channels is linked
      to various physiological and pathological processes, such as memory, learning,
      fear, anxiety, ischemia, and multiple sclerosis to name a few, so their potential
      as therapeutic targets is increasing. This review focuses on recent advances that
      have helped us to better understand the role played by ASICs in different
      pathologies related to neurodegenerative diseases, inflammatory processes, and
      pain.

PMID- 29056833
TI  - Filamentary field-aligned currents at the polar cap region during northward
      interplanetary magnetic field derived with the Swarm constellation.
AB  - ESA's Swarm constellation mission makes it possible for the first time to
      determine field-aligned currents (FACs) in the ionosphere uniquely. In particular
      at high latitudes, the dual-satellite approach can reliably detect some FAC
      structures which are missed by the traditional single-satellite technique. These
      FAC events occur preferentially poleward of the auroral oval and during times of
      northward interplanetary magnetic field (IMF) orientation. Most events appear on
      the nightside. They are not related to the typical FAC structures poleward of the
      cusp, commonly termed NBZ. Simultaneously observed precipitating particle
      spectrograms and auroral images from Defense Meteorological Satellite Program
      (DMSP) satellites are consistent with the detected FACs and indicate that they
      occur on closed field lines mostly adjacent to the auroral oval. We suggest that
      the FACs are associated with Sun-aligned filamentary auroral arcs. Here we
      introduce in an initial study features of the high-latitude FAC structures which
      have been observed during the early phase of the Swarm mission. A more systematic
      survey over longer times is required to fully characterize the so far undetected
      field aligned currents.

PMID- 29056834
TI  - Recent Advances in the Pauson-Khand Reaction.
AB  - The Pauson-Khand [2+2+1] cycloaddition of alkynes, alkenes, and carbon monoxide
      has been a vibrant area of research for more than 40 years. This review
      highlights recent achievements in the Pauson-Khand reaction, particularly in
      catalytic and asymmetric variants. Discussion of regioselectivity and advances in
      substrate scope is also presented.

PMID- 29056835
TI  - Reusable High Aspect Ratio 3-D Nickel Shadow Mask.
AB  - Shadow Mask technology has been used over the years for resistless patterning and
      to pattern on unconventional surfaces, fragile substrate and biomaterial. In this
      work, we are presenting a novel method to fabricate high aspect ratio (15:1)
      three-dimensional (3D) Nickel (Ni) shadow mask with vertical pattern length and
      width of 1.2 mm and 40 MUm respectively. The Ni shadow mask is 1.5 mm tall and
      100 MUm wide at the base. The aspect ratio of the shadow mask is 15. Ni shadow
      mask is mechanically robust and hence easy to handle. It is also reusable and
      used to pattern the sidewalls of unconventional and complex 3D geometries such as
      microneedles or neural electrodes (such as the Utah array). The standard Utah
      array has 100 active sites at the tip of the shaft. Using the proposed high
      aspect ratio Ni shadow mask, the Utah array can accommodate 300 active sites, 200
      of which will be along and around the shaft. The robust Ni shadow mask is
      fabricated using laser patterning and electroplating techniques. The use of Ni 3D
      shadow mask will lower the fabrication cost, complexity and time for patterning
      out-of-plane structures.

PMID- 29056836
TI  - Prevention of Sudden Cardiac Death in Children and Young Adults.
AB  - In the present review, we summarize current approaches to the prevention of
      sudden cardiac death (SCD) in children and young adults, focusing on age less
      than 35 years. SCD in the young is rare, but devastating from the societal
      perspective. While coronary artery disease is the main etiology of SCD in the
      older age groups, conditions such as cardiomyopathies and electrical
      channelopathies are more likely to be found in the young. In the majority of
      younger cases, cardiac arrest can be the first recognized manifestation of the
      underlying cardiac pathology, although some have experienced cardiovascular
      symptoms prior to the SCD. Since identification of a cardiac disease is pivotal
      for implementation of appropriate preventive measures, measures such as
      electrocardiographic screening in subpopulations such as athletes have been
      proposed. However, these efforts are impeded by the large number of individuals
      needed to test in order to find one with cardiac disease, leading to significant
      rates of false positive findings and high costs. When a high-risk cardiac
      condition is identified in a young person, measures of lifestyle modification,
      appropriate medical treatment and ICD implantation in selected individuals based
      on risk stratification are warranted. Nevertheless, the benefits of lifelong ICD
      therapy need to be balanced with long-term complications and quality of life.

PMID- 29056837
TI  - Impact of a Father Figure's Presence in the Household on Children's Psychiatric
      Diagnoses and Functioning in Families at High Risk for Depression.
AB  - The consequences of living in single-parent households on children's wellbeing
      are well documented, but less is known about the impact of living in single
      mother households among children with high familial risk for depression.
      Utilizing data from an ongoing three-generation study of high-risk families, this
      preliminary study examined a sample of 161 grandchildren of probands diagnosed
      with major depressive disorder, comparing those in single-parent households to
      those in dual-parent households with household status defined as the full-time
      presence of a resident male in the home. High-risk children were compared across
      households in terms of psychiatric diagnoses (measured by Schedule for Affective
      Disorders and Schizophrenia for School-Age Children; K-SADS-PL) and global
      functioning (assessed by Global Assessment Scale, child version; C-GAS). Results
      indicated that high-risk children in single-parent households had 4.7 times
      greater odds for developing a mood disorder and had significantly lower mean C
      GAS scores (p = 0.01) compared to those in dual-parent households. Differences
      remained significant when controlling for household income, child's age, and
      either parent's depression status. There were no significant differences between
      high-risk children across households when household status was instead defined as
      legal marital status. This study has several limitations: sample size was small,
      pro-bands were recruited from a clinical population, and participants had not
      passed completely through the period of risk for adult psychiatric disorders.
      These findings point towards the importance of identifying and closely monitoring
      children at risk for depression, particularly if they reside in households
      without a resident father figure.

PMID- 29056838
TI  - Maternal and Paternal Influences on Children's Coping with Cancer-Related Stress.
AB  - Childhood cancer is a significant source of stress for children and families, and
      children's coping with cancer-related stress is a key predictor of emotional
      adjustment. To extend understanding of the determinants of children's coping with
      cancer-related stress, this study examined whether mothers' and fathers'
      functioning after their child's diagnosis-including coping and depressive
      symptoms-is predictive of children's coping over time. Participants included 166
      children (Mage = 13.47, SD = 2.47, 51.2% female), 161 mothers, and 83 fathers.
      Approximately two months post-diagnosis (T1), parents reported on their coping
      and depressive symptoms. At T1 and approximately 12 months later (T2), children
      reported on their coping. Results indicated that mothers' coping and depressive
      symptoms were correlated with children's coping at T1; fathers' coping and
      depressive symptoms were generally not associated with children's coping at T1.
      Hierarchical regression analyses revealed that fathers' secondary control coping
      (i.e., coping aimed at adapting to cancer-related stress) predicted higher levels
      of secondary control coping in children over time. Mothers' depressive symptoms
      predicted lower levels of secondary control coping over time in girls, and
      fathers' depressive symptoms predicted lower levels of secondary control coping
      over time across sex. Parents' functioning after their child's cancer diagnosis
      may shape how children cope with cancer-related stress. Parents' coping and
      depressive symptoms may be important targets for interventions aiming to promote
      positive adjustment in children with cancer.

PMID- 29056839
TI  - When Mothers' Work Matters for Youths' Daily Time Use: Implications of Evening
      and Weekend Shifts.
AB  - Drawing upon the work-home resources model, this study examined the implications
      of mothers' evening and weekend shifts for youths' time with mother, alone, and
      hanging out with peers unsupervised, with attention to both the amount and day-to
      day consistency of time use. Data came from 173 mothers who worked in the long
      term care industry and their youths who provided daily diaries. Multilevel
      modeling revealed that youths whose mothers worked more evening shifts on average
      spent less time with their mothers compared to youths whose mothers worked fewer
      evening shifts. Youths whose mothers worked more weekend shifts, however, spent
      more time with their mothers and exhibited less consistency in their time in all
      three activity domains compared to youths whose mothers worked fewer weekend
      shifts. Girls, not boys, spent less time alone on days when mothers worked
      weekend shifts than on days with standard shifts. Older but not younger
      adolescents spent more time hanging out with friends on evening and weekend shift
      days, and their unsupervised peer time was less consistent across days when
      mothers worked more evening shifts. These effects adjusted for sociodemographic
      and day characteristics, including school day, number of children in the
      household, mothers' marital status and work hours, and time with fathers. Our
      results illuminate the importance of the timing and day of mothers' work for
      youths' daily activities. Future interventions should consider how to increase
      mothers' resources to deal with constraints on parenting due to their work during
      nonstandard hours, with attention to child gender and age.

PMID- 29056840
TI  - The Multidimensional Assessment of Parenting Scale (MAPS): Development and
      Psychometric Properties.
AB  - The aim of the current study was to create a new measure of parenting practices,
      constituted by items from already established measures, to advance the
      measurement of parenting practices in clinical and research settings. Five stages
      were utilized to select optimal parenting items, establish a factor structure
      consisting of positive and negative dimensions of parenting, meaningfully
      consider child developmental stage, and ensure strong psychometric properties
      (reliability and validity) of the final measure. A total of 1,790 parents (44%
      fathers) were recruited online through Amazon's Mechanical Turk for three
      cohorts: Stages 1 (N = 611), 2 (N = 615), and 3 (N = 564). Each sample was
      equally divided by child developmental stage: Young childhood (3 to 7 years old),
      middle childhood (8 to 12 years old), and adolescence (13 to 17 years old).
      Through the five-stage empirical approach, the Multidimensional Assessment of
      Parenting Scale (MAPS) was developed, successfully achieving all aims. The MAPS
      factor structure included both positive and negative dimensions of
      warmth/hostility and behavioral control that were appropriate for parents of
      children across the developmental span. The MAPS demonstrated strong reliability
      and longitudinal analyses provided initial support for the validity of MAPS
      subscales.

PMID- 29056841
TI  - Assessing Coparenting Relationships in Daily Life: The Daily Coparenting Scale (D
      Cop).
AB  - We describe the development and validation of the Daily Coparenting Scale (D
      Cop), a measure of parents' perceptions of daily coparenting quality, to address
      the absence of such a daily measure in the field. A daily measure of coparenting
      can help us to better identify and optimize specific mechanisms of short-term
      change in family processes as well as examine within-person variability and
      processes as they are lived by participants in their everyday lives. Mothers and
      fathers, from 174 families with at least one child age 5 or younger, completed a
      14-day diary study. Utilizing multilevel factor analysis, we identified two daily
      coparenting factors at both the between- and within-person level: positive and
      negative daily coparenting. The reliabilities of the overall D-Cop and individual
      positive and negative subscales were good, and we found that parents' reports of
      coparenting quality fluctuated on a daily basis. Also, we established the initial
      validity of the D-Cop, as scores related as expected to (a) an existing and
      already validated measure of coparenting and to (b) couple relationship quality,
      depressive symptoms, and child behavior problems. Further, fluctuations in daily
      couple relationship feelings related to fluctuations in daily coparenting
      quality. The D-Cop and its subscales functioned almost identically when only
      utilizing 7 days of data instead of 14 days. We call for future work to study day
      by-day fluctuations and dynamics of coparenting to better illuminate family
      processes that lead to child and family outcomes in order to improve the efficacy
      of family interventions.

PMID- 29056842
TI  - Forecasting Disparities with Early Substance-Use Milestones.
AB  - Substance use contributes to health disparities across race/ethnicity, gender,
      and socioeconomic status (SES). Although adolescent research indicates group
      based differences in regular use, few studies have examined patterns when
      initiation is just beginning. Using a sample of 917 Rhode Island middle schools
      students (54% female, 26% non-Hispanic White), we collected demographic
      information at baseline (M age 12.2); we then examined ever-puff (cigarettes),
      ever-sip (alcohol), and ever-use (marijuana) behaviors three years later. For
      cigarette use, we found differences based on SES and race/ethnicity (prevalence
      was particularly high among Native American youths). Marijuana use was associated
      with lower SES, and alcohol use was higher among females than males. Overall,
      findings indicate racial/ethnic-, gender- and SES-based differences in early
      substance-use milestones. From a prevention standpoint, it is important to
      evaluate differences not only in heavy substance use, but in early milestones, as
      they may set the course for health disparities across the lifespan.

PMID- 29056843
TI  - Comparison of the Diagnostic Yield of EUS Needles for Liver Biopsy: Ex Vivo
      Study.
AB  - BACKGROUND AND AIMS: EUS-guided liver biopsy is an emerging method of liver
      tissue acquisition which is safe and had been shown to produce excellent
      histological yield. There is limited data comparing the diagnostic yield of
      different FNA needles. We aimed to compare the diagnostic performance of four
      commercially available 19-gauge FNA needles. METHODS: Four FNA needles and one
      percutaneous needle were used to perform liver biopsies on two human cadaveric
      livers: Cook Echotip ProcoreTM, Olympus EZ Shot 2TM, Boston Scientific Expect
      SlimlineTM, Covidien SharkCoreTM, and an 18-gauge percutaneous needle (TruCoreTM,
      Argon Medical Devices). Each needle obtained biopsies by three, six, and nine
      complete back-and-forth motions of the needle ("throw") with a fanning technique.
      The combined lengths of specimen fragments and the total number of complete
      portal tracts (CPT) were measured by a blinded pathologist. One-way analysis of
      variance (ANOVA) and Bonferroni correction were used for statistical analysis.
      RESULTS: A total of 52 liver biopsies were performed. The Covidien SharkCore
      needle had significantly greater number of CPT compared to other FNA needles. The
      number of "throws" did not impact the number of CPT significantly. There was no
      statistically significant difference in mean total specimen length between each
      FNA needle type. CONCLUSION: The Covidien SharkCore needle produced superior
      histological specimen by capturing more CPT, possibly due to its unique needle
      design.

PMID- 29056844
TI  - Extended Cystogastrostomy with Hydrogen Peroxide Irrigation Facilitates
      Endoscopic Pancreatic Necrosectomy.
AB  - INTRODUCTION: Walled-off pancreatic necrosis (WOPN) is a major complication of
      acute pancreatitis. We hypothesized that an extended (2 cm) cystogastrostomy
      opening combined with hydrogen peroxide irrigation can increase the success of
      endoscopic necrosectomy and decrease the number of required endoscopic
      interventions. The aim of the study is to assess the safety and feasibility of
      the technique in the management of WOPN. METHODS: This is a retrospective chart
      review of all cases that underwent EUS with extended cystogastrostomy and
      hydrogen peroxide irrigation prior to necrosectomy in a tertiary referral medical
      center. Clinical success was defined as complete resolution of the cyst cavity or
      a cyst cavity less than 2 cm in size on follow-up imaging. RESULTS: 19 patients
      satisfied the inclusion criteria. The mean size of the walled-off cavity was 11 +
      0.9 cm. Technical success of the procedure was 100%. The median number of
      necrosectomy sessions was 2 (range 1 to 7). Cavity resolution was noted in 18 out
      of 19 patients resulting in a clinical success of 94.7%. The median follow-up
      period was 12 months. The adverse events rate in our cohort was 15.7%.
      CONCLUSION: Extended cystogastrostomy coupled with hydrogen peroxide irrigation
      of WOPN cavity is safe and feasible.

PMID- 29056845
TI  - Usability of a Smartphone Application to Support the Prevention and Early
      Intervention of Anxiety in Youth.
AB  - Anxiety disorders are among the most common psychiatric problems in youth, fail
      to spontaneously remit, and place some youth at risk for additional behavioral
      and emotional difficulties. Efforts to target anxiety have resulted in evidence
      based interventions but the resulting prevention effects are relatively small,
      often weakening over time. Mobile health (mHealth) tools could be of use to
      strengthen the effects of anxiety prevention efforts. Although a large number of
      mHealth apps have been developed, few have been evaluated in terms of usability
      prior to clinical effectiveness testing. Because usability is one of the main
      barriers to mHealth usage and adoption, the objective of this research was to
      evaluate the usability of a smartphone application (app) corresponding to an
      indicated prevention and early intervention targeting youth anxiety. To
      accomplish this, 132 children (M age = 9.65; 63% girls) and 45 service providers
      (M age = 29.13, 87% female) rated our app along five established dimensions of
      usability (ease of use, ease of learning, quality of support information,
      satisfaction, and stigma) using a standardized group-based testing protocol.
      Findings showed that the app was highly and positively rated by both youth and
      providers, with some variations (lower ratings when errors occurred). Path
      analyses findings also showed that system understanding was significantly related
      to greater system satisfaction, but that such relation occurred through the
      quality of support information offered by the app.

PMID- 29056846
TI  - A Cultural Adaptation of Dialectical Behavior Therapy in Nepal.
AB  - Growing evidence exists on the potential for adapting evidence-based
      interventions for low- and-middle-income countries (LMIC). One opportunity that
      has received limited attention is the adaptation of psychotherapies developed in
      high-income countries (HIC) based on principles from LMIC cultural groups.
      Dialectical behavior therapy (DBT) is one such treatment with significant
      potential for acceptability in South Asian settings with high suicide rates. We
      describe a tri-phasic approach to adapt DBT in Nepal that consists of qualitative
      interviews with major Nepali mental health stakeholders (Study 1), an adaptation
      workshop with 15 Nepali counselors (Study 2), and a small-scale treatment pilot
      with eligible clients in one rural district (Study 3). Due to low literacy
      levels, distinct conceptualizations of mind and body, and program adherence
      barriers, numerous adaptations were required. DBT concepts attributable to Asian
      belief systems were least comprehensible to clients. However, the 82% program
      completion rate suggests utility of a structured, skills-based treatment. This
      adaptation process informs future research regarding the effectiveness of
      culturally adapted DBT in South Asia.

PMID- 29056847
TI  - Examining Services for Young Children with Autism Spectrum Disorder: Parent
      Satisfaction and Predictors of Service Utilization.
AB  - Autism spectrum disorder (ASD) is the fastest growing group of neurodevelopmental
      disorders in childhood. Earlier detection means an increased need for early
      intervention and other educational services. This study examined what services a
      sample of young children with ASD received, what variables predicted service
      utilization, and how satisfied parents were with the services. Sixty children (2
      7 years) and their families from the Northwestern United States participated in
      the study. Results suggest that, on average, children received 13 hours of
      educational and therapeutic services per week, with younger children receiving
      fewer services than older children. Child age, atypical behavior, and family
      income predicted number of service hours received. Children's adaptive behavior
      and autism symptoms did not predict service hours. Although services received
      were, by most standards, minimal and far below best practice recommendations,
      parents reported high satisfaction, especially for their toddlers and preschool
      aged children. Implications and future directions are described.

PMID- 29056848
TI  - Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin
      e6.
AB  - Syntheses of three new chlorin e6 conjugates for PDT of tumors are reported. One
      of the new compounds 17 is conjugated with lysine at the 131-position, but the
      others are mono-conjugated 14 or diconjugated 15 with the non-amino acid species
      ethanolamine. Cellular experiments with the three new compounds and previously
      synthesized non-amino acid 152-conjugates (7-10), 131-monoconjugates 14, 16, and
      a 131,152-diconjugate 12 are reported. In vitro cytotoxicity experiments show
      that the 131-conjugates are more toxic than the 152-conjugates, and the most
      toxic derivative (dark- and photo-toxicity) is the 131-ethylenediamine conjugate
      11. The most useful PDT photosentitizers appear to be the ethanolamine
      derivatives, conjugated at the 152- and the 131,152-positions; these show high
      phototoxicity but relatively low dark toxicity compared with 11, and also the
      highest dark/photo cytotoxicity ratios.

PMID- 29056850
TI  - The Relationships Among Childhood Maltreatment, Emotion Regulation, and Sexual
      Risk-Taking in Men from Urban STD Clinics.
AB  - This study sought to examine the relationships among emotion regulation
      difficulties, childhood maltreatment, and risky sexual behavior in a sample of
      320 heterosexual men recruited from urban STD clinics. Overall childhood
      maltreatment and several specific types of child abuse were significantly
      associated with emotion dysregulation, number of sexual partners, and STI
      diagnosis. There was evidence of an additive effect of multiple forms of
      maltreatment on difficulties with emotion regulation and sexual risk-taking.
      Impulse control difficulties and access to emotion regulation strategies, two
      components of emotion dysregulation, were related to measures of risky sexual
      behavior. Furthermore, limited access to emotion regulation strategies mediated
      the relationship between frequency of childhood sexual abuse and a greater number
      of lifetime sexual partners. This study has important implications for developing
      effective interventions to reduce the spread of STI's and HIV by expanding affect
      regulation and distress tolerance strategies among men who have experienced
      childhood maltreatment.

PMID- 29056849
TI  - Common Sense Illness Beliefs of Diabetes among At-Risk Latino College Students.
AB  - This study examined the validity of the Implicit Model of Illness Questionnaire
      (IMIQ - Schiaffino & Cea, 1995) when used with Latino college students (n = 156;
      34% male, 66% female) who are at-risk for developing diabetes due to family
      history of this disease. An exploratory principal-axis factor analysis yielded
      four significant factors - curability, personal responsibility, symptom
      variability/seriousness, and personal attributions - which accounted for 35% of
      variance and reflected a psychosocial-biomedical common sense perspective of
      diabetes. Factor-based analyses revealed differences in diabetes illness beliefs
      based on students' age, generational status, acculturation orientation, and
      disease experience of the afflicted relative.

PMID- 29056851
TI  - Evaluation of long-term conservation agriculture and crop intensification in rice
      wheat rotation of Indo-Gangetic Plains of South Asia: Carbon dynamics and
      productivity.
AB  - In the context of deteriorating soil health, stagnation of yield in rice-wheat
      cropping system (RWCS) across Indo- Gangetic plains (IGP) and environmental
      pollution, a long term field experiment was conducted during 2009-2016 taking
      four crop scenarios with conservation agriculture (CA), crop intensification and
      diversified cropping as intervening technology aiming to evaluate the
      sustainability of the systems. Scenario 1 (S1) represented conventional farmers'
      practice of growing rice and wheat with summer fallow. In scenario 2 (S2) and
      scenario 3 (S3), legume crop was taken along with rice and wheat with partial CA
      and full CA, respectively. Conventional RWCS was replaced with rice-potato +
      maize- cowpea cropping system with partial CA in scenario 4 (S4). The S3 scenario
      registered highest total organic carbon (TOC) stock of 47.71 Mg C ha-1 and
      resulted in significant increase of 14.57% over S1 (Farmer's practice) in 0-30 cm
      soil depth after 7 years of field trial. The S4 scenario having intensified
      cropping systems recorded lowest TOC of 39.33 Mg C ha-1 and resulted in
      significant depletion of 17.56% in C stock with respect to S3 in 0-30 cm soil
      depth. The TOC enrichment was higher in S2, S3 and S4 scenario in the surface
      soil (0-10 cm) compared to S1. At lower depth (20-30 cm), the TOC enrichment was
      significantly higher in S2 (12.82 Mg C ha-1) and S3 (13.10 Mg C ha-1 soil) over
      S1 scenario. The S2 and S3 scenario recorded highest increased allocation of TOC
      (3.55 and 6.13 Mg C ha-1) to passive pool over S1. The S2 (15.72 t ha-1), S3
      (16.08 t ha-1) and S4 (16.39 t ha-1) scenarios recorded significantly higher
      system rice equivalent yield over S1 (10.30 t ha-1). Among the scenarios, S3
      scenario had greater amount of total soil organic carbon, passive pool of carbon
      and higher system rice equivalent yield, thus, is considered the best cropping
      management practice to maintain soil health and food security in the middle IGP.

PMID- 29056852
TI  - Analysis of Safety-Related Regulatory Actions for New Drugs in Japan by Nature of
      Identified Risks.
AB  - BACKGROUND: Mechanisms underlying safety events may be heterogeneous and depend
      on conditions of development and marketing, including the populations studied in
      clinical trials and the amount of data required for approval, especially under
      pathways for accelerated access. OBJECTIVE: This study was conducted to
      investigate possible factors affecting the first post-marketing safety-related
      regulatory actions (SRRAs) after launch of new drugs in Japan. METHODS: We
      studied 338 new molecular entities (NMEs) approved in Japan between 2004 and
      2014. We focused on three different types of SRRAs: (1) all-SRRAs (i.e. SRRAs
      from domestic cases and other countries), (2) domestic-SRRAs (i.e. SRRAs from
      domestic cases) and (3) domestic unknown-SRRAs (i.e. SRRAs of unknown risks from
      domestic cases). Occurrences of the three types of SRRAs were analyzed using
      Kaplan-Meier analysis and Cox-regression. RESULTS: SRRAs tended to occur sooner
      for NMEs launched in recent years versus those launched towards the beginning of
      the study period. Risk of SRRA was high for antineoplastics. Drugs for
      cardiovascular diseases, central nervous system, and diabetes had positive
      associations with all-SRRAs, but the associations were weaker with domestic
      SRRAs. Domestic-SRRAs were more likely for drugs with relatively novel modes of
      action (MOAs). Longer lag to Japanese launch after first global launch
      significantly lowered SRRA risks. While most of the variables showed similar
      associations across the three types of SRRAs, adoption of bridging strategies
      showed higher risks only for domestic-SRRAs, not for all-SRRAs. FDA safety
      labeling changes and non-orphan priority review drugs presented higher domestic
      SRRA risks. The number of adverse drug reactions (ADRs) from spontaneous reports
      had positive correlations with the three types of SRRAs, whereas the number from
      company-led surveillance showed no association. CONCLUSIONS: Our results
      indicated that global clinical development pathways and marketing status should
      be considered more seriously in implementing locally optimized pharmacovigilance
      activities. Caution may be needed not only for drugs with novel MOAs, but also
      for drugs for which local dose-finding studies have been skipped, expedited
      review status has been given, timing of launch is close to those in the USA and
      the EU, and spontaneous reports rather than company-lead surveillance suggest
      possible safety risks.

PMID- 29056853
TI  - Evaluation of Risk-Minimization Activities for Cyproterone Acetate 2
      mg/Ethinylestradiol 35 ug: A Cross-Sectional Physician Survey.
AB  - BACKGROUND: Cyproterone acetate 2 mg/ethinylestradiol 35 ug, an
      estrogen/progestogen treatment with anti-androgenic properties, shares a
      thromboembolism risk with combined hormonal contraceptives. Educational materials
      (i.e., direct healthcare professional communication, patient information card,
      prescriber checklist) were distributed to physicians to increase risk awareness.
      OBJECTIVE: The objective of this study was to measure physician knowledge of
      thromboembolism risk of cyproterone acetate 2 mg/ethinylestradiol 35 ug and
      ascertain whether physicians received the educational materials. METHODS: A cross
      sectional web-based physician survey of recent prescribers of cyproterone acetate
      2 mg/ethinylestradiol 35 ug in Austria, the Czech Republic, France, the
      Netherlands, and Spain was conducted. Sampling targets for physician specialty
      were based on country-specific prescribing patterns. Frequency of correct
      responses was calculated for 14 knowledge questions. RESULTS: Among 759 physician
      respondents (37% of obstetricians/gynecologists, 42% of general practitioners,
      20% of dermatologists), 51% received one or more of three educational materials.
      Knowledge was highest (>=80%) for symptoms of possible deep vein thrombosis,
      pulmonary embolism, and cerebrovascular accident; most important risk factors for
      thrombosis; use in smokers; indication for moderate-to-severe acne; and
      understanding that cyproterone acetate 2 mg/ethinylestradiol 35 ug should not be
      used for contraception alone. Knowledge varied for contraindications, myocardial
      infarction symptoms, other risk factors for thrombosis, instructions regarding
      anticipated prolonged immobilization, and selected concomitant medical
      conditions. Knowledge was lower regarding prescribing cyproterone acetate 2
      mg/ethinylestradiol 35 ug for acne only after failure of topical therapy or
      systemic antibiotics. Generally, knowledge did not vary by physician specialty,
      receipt of educational materials, number of patients prescribed cyproterone
      acetate 2 mg/ethinylestradiol 35 ug in the previous 3 months, and years in
      practice. CONCLUSIONS: Knowledge was generally high for thromboembolism risk and
      varied for more complex or infrequent topics.

PMID- 29056854
TI  - Postoperative radiotherapy for invasive micropapillary carcinoma of the breast:
      an analysis of Surveillance, Epidemiology, and End Results database.
AB  - INTRODUCTION: Invasive micropapillary carcinoma (IMPC) of the breast poses a high
      risk of locoregional recurrence, and postoperative radiotherapy (PORT) may be
      beneficial in IMPC. Hence, we determined the clinical value of PORT in IMPC
      patients. PATIENTS AND METHODS: We assessed clinicopathological factors extracted
      from the Surveillance, Epidemiology, and End Results database (2004-2013).
      Univariate and multivariate Cox proportional hazards regressions were performed
      to assess the independent prognostic factors on breast cancer-specific survival
      (BCSS) and overall survival (OS). RESULTS: Of the 881 study patients, 444 (50.4%)
      and 437 (49.6%) underwent breast-conserving surgery (BCS) and mastectomy (MAST),
      respectively, of whom 357 (80.4%) and 153 (35.0%) underwent PORT, respectively.
      Patients with young age, large tumor size, or advanced nodal stage were more
      likely to undergo MAST and PORT compared with MAST alone. Patients with
      progesterone receptor-positive disease were more likely to receive BCS and PORT
      compared with BCS alone. The 5-year BCSS and OS were 95.7% and 90.9%,
      respectively. On multivariate analyses, tumor size, histological grade, and
      estrogen receptor status were independent predictors of BCSS and OS. The types of
      surgical procedures (MAST vs. BCS) were not an independent predictor of survival
      outcomes. Patients who underwent MAST with or without PORT had similar BCSS and
      OS in the multivariate analyses. Those who underwent BCS plus PORT did not have
      better BCSS and OS than those who underwent BCS alone. In the low-, intermediate
      , and high-risk groups, PORT was not associated with better BCSS and OS than non
      PORT groups in patients who received BCS or MAST. CONCLUSION: IMPC has favorable
      BCSS and OS. Regardless of the types of surgical procedures (MAST or BCS), PORT
      groups were not inferior to non-PORT groups on BCSS and OS.

PMID- 29056855
TI  - Emerging combination therapies for metastatic colorectal cancer - impact of
      trifluridine/tipiracil.
AB  - Patients with metastatic colorectal cancer (mCRC) are surviving longer now than
      ever before, but mortality rates are still high and more effective therapies are
      clearly needed. For patients with disease that is refractory to
      fluoropyrimidines, oxaliplatin, irinotecan, and biologic agents targeting the
      vascular endothelial growth factor and epidermal growth factor receptor pathways,
      novel treatment options trifluridine/tipiracil (TAS-102) and regorafenib can be
      effective disease stabilizers. However, objective clinical responses are rare and
      toxicities are manageable but common. In order to tackle poor clinical responses
      to TAS-102, there is an ongoing effort to effectively combine this drug with
      other agents, particularly those targeting angiogenesis. Certain subpopulations
      appear to benefit more than others from TAS-102; those that benefit often have
      underlying genetic defects in DNA repair pathways and/or develop neutropenia. In
      this review, we focus on the role of TAS-102 in the treatment of mCRC, including
      its use in combination with other agents, potential predictive biomarkers of
      response to TAS-102, and possible future directions.

PMID- 29056857
TI  - The death of ink: the value of typing skills as an addition to the medical school
      curriculum.

PMID- 29056856
TI  - Surgical resection of a primary tumor improves survival of metastatic pancreatic
      cancer: a population-based study.
AB  - INTRODUCTION: Pancreatic cancer is a lethal disease with a very poor prognosis.
      This study investigates survival of patients diagnosed with metastatic pancreatic
      cancer (mPC) based on local treatment of the primary tumor. METHODS: Patients
      diagnosed with stage IV mPC between 2004 and 2013 were identified from the
      Surveillance, Epidemiology and End Results (SEER) database. Cancer-specific
      survival (CSS) and overall survival (OS) were examined. CSS and OS were examined
      by using the Kaplan-Meier method with the log-rank test. Multivariable survival
      analyses of CSS and OS were conducted using the Cox proportional hazard model.
      RESULTS: A total of 28918 patients with mPC were included in this analysis. There
      were 467 patients who received surgical resection (1.6%) and 28451 patients who
      did not (98.4%). Patients who were younger than 70 years (odds ratio [OR]=1.45,
      95% CI=1.04-2.03, p=0.03), diagnosed from 2004 to 2008 (OR=1.49, 95% CI=1.25
      1.80, p<0.001), female (OR=1.31, 95% CI=1.08-1.58, p<0.001), married (OR=1.56,
      95% CI=1.27-1.90, p<0.001), at T3 stage (OR=3.53, 95% CI=1.10-11.37, p=0.035), at
      N1 stage (OR=2.05, 95% CI=1.68-2.50, p<0.001), presenting histological types
      other than adenocarcinoma (OR=2.04, 95% CI=1.43-2.94, p<0.001), and with tumor of
      the pancreatic head (OR=1.90, 95% CI=1.27-2.82, p=0.002) were more likely to be
      treated with surgical resection. The results of multivariate analysis showed that
      surgical resection of the primary tumor was associated with CSS (hazard ratio
      [HR]=0.58, 95% CI=0.52-0.64, p<0.001) and OS (HR=0.59, 95% CI=0.53-0.65, p<0.001)
      benefits. In addition, not receiving chemotherapy (HR=2.33, 95% CI=2.27-2.39,
      p<0.001), age >50 years (HR=1.25, 95% CI=1.09-1.42, p=0.001), male (HR=1.121, 95%
      CI=1.09-1.15, p<0.001), black ethnicity (HR=1.11, 95% CI=1.1-1.15, p<0.001),
      unmarried (HR=1.20, 95% CI=1.17-1.23, p<0.001), histological type of
      adenocarcinoma (HR=1.18, 95% CI=1.14-1.22, p<0.001), and primary site other than
      the pancreatic head (HR=1.08, 95% CI=1.05-1.11, p<0.001) are factors associated
      with poor survival. CONCLUSION: This study reveals that local treatment has the
      primary benefit of both CSS and OS in patients with mPC. These results may guide
      the management of this patient population.

PMID- 29056858
TI  - Innovative partnerships to advance public health training in community-based
      academic residency programs.
AB  - Collaborative partnerships between community-based academic residency training
      programs and schools of public health, represent an innovative approach to
      training future physician leaders in population management and public health. In
      Kaiser Permanente Northern California, development of residency-Masters in Public
      Health (MPH) tracks in the Internal Medicine Residency and the Pediatrics
      Residency programs, with MPH graduate studies completed at the University of
      California Berkeley School of Public Health, enables physicians to integrate
      clinical training with formal education in epidemiology, biostatistics, health
      policy, and disease prevention. These residency-MPH programs draw on more than 50
      years of clinical education, public health training, and health services research
      - creating an environment that sparks inquiry and added value by developing
      skills in patient-centered care through the lens of population-based outcomes.

PMID- 29056860
TI  - Brain derived neurotrophic factor and serotonin transporter binding as markers of
      clinical response to fluoxetine therapy in children with autism.
AB  - Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), has shown favorable
      effects in some children with autism. There are no previous studies evaluating
      the connection between clinical outcome and markers of clinical response to
      fluoxetine treatment. We examined serum brain derived neurotrophic factor (BDNF)
      concentrations and serotonin transporter (SERT) binding in the medial frontal
      cortex and midbrain, measured by single photon emission computed tomography
      (SPECT) scanning, in a group of 13 autistic children and adolescents (12 males,
      one female; age 5-16 years), who were treated for six months with fluoxetine at a
      dose range of 10-40 mg/day. Clinical response was evaluated by the Autism
      Treatment Evaluation Checklist (ATEC). Serum concentrations of BDNF and SERT
      binding were measured at baseline and two months after termination of fluoxetine
      treatment. At baseline, before starting fluoxetine treatment, the serum
      concentration of BDNF had a bimodal distribution in the autism group with either
      a low concentration (n = 8, mean 1497 pg/mL) or a high concentration (n = 5, mean
      14062 pg/mL) with respect to controls (n = 15, mean 9652 pg/mL), and SERT binding
      was uniformly low in the autistic subjects in medial frontal cortex and midbrain.
      Fluoxetine treatment led to positive effects in several aspects of communication,
      socialization and cognitive awareness, with 6 out 13 subjects being particularly
      good responders. These six also had a significant decrease in BDNF (p = 0.03) and
      minimal change in SERT binding after therapy. The other 7 subjects showed a trend
      towards an increase in BDNF and SERT binding. Our results indicate that
      fluoxetine may improve core autistic symptoms, and that this clinical response is
      linked to a decrease in serum BDNF.

PMID- 29056859
TI  - Efficacy and Safety of Transdermal Buprenorphine versus Oral
      Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after
      Spinal Surgery.
AB  - PURPOSE: Control of persistent pain following spinal surgery is an unmet clinical
      need. This study compared the efficacy and safety of buprenorphine transdermal
      system (BTDS) to oral tramadol/acetaminophen (TA) in Korean patients with
      persistent, moderate pain following spinal surgery. METHODS: Open-label,
      interventional, randomized multicenter study. Adults with persistent
      postoperative pain (Numeric Rating Scale [NRS] >= 4 at 14-90 days postsurgery)
      were enrolled. Patients received once-weekly BTDS (n = 47; 5 MUg/h titrated to 20
      MUg/h) or twice-daily TA (n = 40; tramadol 37.5 mg/acetaminophen 325 mg, one
      tablet titrated to 4 tablets) for 6 weeks. The study compared pain reduction with
      BTDS versus TA at week 6. Quality of life (QoL), treatment satisfaction,
      medication compliance, and adverse events (AEs) were assessed. FINDINGS: At week
      6, both groups reported significant pain reduction (mean NRS change: BTDS -2.02;
      TA -2.76, both P < 0.0001) and improved QoL (mean EQ-5D index change: BTDS 0.10;
      TA 0.19, both P < 0.05). The BTDS group achieved better medication compliance
      (97.8% versus 91.0%). Incidence of AEs (26.1% versus 20.0%) and adverse drug
      reactions (20.3% versus 16.9%) were comparable between groups. IMPLICATIONS: For
      patients with persistent pain following spinal surgery, BTDS is an alternative to
      TA for reducing pain and supports medication compliance. This trial is registered
      with Clinicaltrials.gov: NCT01983111.

PMID- 29056861
TI  - Comparison of DMSP and SECS region-1 and region-2 ionospheric current boundary.
AB  - The region-1 and region-2 boundary has traditionally been identified using data
      from a single spacecraft crossing the auroral region and measuring the large
      scale changes in the cross track magnetic field. With data from the AUTUMN,
      CANMOS, CARISMA, GIMA, DTU MGS, MACCS, McMAC, STEP, THEMIS, and USGS ground
      magnetometer arrays we applied a state-of-art technique based on spherical
      elementary current system (SECS) method developed by Amm and Viljanen (1999) in
      order to calculate maps of region-1 and region-2 current system over the North
      American and Greenland auroral region. Spherical elementary current (SEC)
      amplitude (proxy for vertical currents) maps can be inferred at 10 s temporal
      resolution, ~1.5 degrees  geographic latitude (Glat), and 3.5 degrees  geographic
      longitude (Glon) spatial resolution. We compare the location of the region-1 and
      region-2 boundary obtained by the DMSP spacecraft with the region-1 and region-2
      boundary observed in the SEC current amplitudes. We find that the boundaries
      typically agree within 0.2 degrees  +/- 1.3 degrees . These results indicate that
      the location of the region-1 and region-2 boundary can reasonably be determined
      from ground magnetometer data. The SECS maps represent a value-added product from
      the magnetometer database and can be used for contextual interpretation in
      conjunction with other missions as well as help with our understanding of
      magnetosphere-ionosphere coupling mechanisms using the ground arrays and the
      magnetospheric spacecraft data.

PMID- 29056862
TI  - Recent language experience influences cross-language activation in bilinguals
      with different scripts.
AB  - PURPOSE: This study aimed to examine whether the phonological information in the
      non-target language is activated and its influence on bilingual processing.
      APPROACH: Using the Stroop paradigm, Mandarin-English bilinguals named the ink
      color of Chinese characters in English in Experiment 1 and named the Chinese
      characters in addition to the color naming in English in Experiment 2. Twenty
      four participants were recruited in each experiment. In both experiments, the
      visual stimuli included color characters (e.g. , hong2, red), homophones of the
      color characters (e.g. , hong2, flood), characters that only shared the same
      syllable segment with the color characters (S+T-, e.g. , hong1, boom), characters
      that shared the same tone but differed in segments with the color characters (S
      T+, e.g. , ping2, bottle), and neutral characters (e.g. , qian1, leading
      through). DATA AND ANALYSIS: Planned t-tests were conducted in which
      participants' naming accuracy rate and naming latency in each phonological
      condition were compared with the neutral condition. FINDINGS: Experiment 1 only
      showed the classic Stroop effect in the color character condition. In Experiment
      2, in addition to the classic Stroop effect, the congruent homophone condition
      (e.g. in red) showed a significant Stroop interference effect. These results
      suggested that for bilingual speakers with different scripts, phonological
      information in the non-target language may not be automatically activated even
      though the written words in the non-target language were visually presented.
      However, if the phonological information of the non-target language is activated
      in advance, it could lead to competition between the two languages, likely at
      both the phonological and lemma levels. ORIGINALITY AND SIGNIFICANCE: This study
      is among the first to investigate whether the translation of a word is
      phonologically encoded in bilinguals using the Stroop paradigm. The findings
      improve our understanding of the underlying mechanism of bilingual processing.

PMID- 29056863
TI  - Estimation of the false discovery proportion with unknown dependence.
AB  - Large-scale multiple testing with correlated test statistics arises frequently in
      many scientific research. Incorporating correlation information in approximating
      false discovery proportion has attracted increasing attention in recent years.
      When the covariance matrix of test statistics is known, Fan, Han & Gu (2012)
      provided an accurate approximation of False Discovery Proportion (FDP) under
      arbitrary dependence structure and some sparsity assumption. However, the
      covariance matrix is often unknown in many applications and such dependence
      information has to be estimated before approximating FDP. The estimation accuracy
      can greatly affect FDP approximation. In the current paper, we aim to
      theoretically study the impact of unknown dependence on the testing procedure and
      establish a general framework such that FDP can be well approximated. The impacts
      of unknown dependence on approximating FDP are in the following two major
      aspects: through estimating eigenvalues/eigenvectors and through estimating
      marginal variances. To address the challenges in these two aspects, we firstly
      develop general requirements on estimates of eigenvalues and eigenvectors for a
      good approximation of FDP. We then give conditions on the structures of
      covariance matrices that satisfy such requirements. Such dependence structures
      include banded/sparse covariance matrices and (conditional) sparse precision
      matrices. Within this framework, we also consider a special example to illustrate
      our method where data are sampled from an approximate factor model, which
      encompasses most practical situations. We provide a good approximation of FDP via
      exploiting this specific dependence structure. The results are further
      generalized to the situation where the multivariate normality assumption is
      relaxed. Our results are demonstrated by simulation studies and some real data
      applications.

PMID- 29056864
TI  - Understanding Curli Amyloid-Protein Aggregation by Hydrogen-Deuterium Exchange
      and Mass Spectrometry.
AB  - Bacteria within Curli biofilms are protected from environmental pressures (e.g.,
      disinfectants, antibiotics), and this is responsible for intractable infections.
      Understanding aggregation of the major protein component of Curli, CsgA, may
      uncover disease-associated amyloidogenesis mechanisms. Here, we report the
      application of pulsed hydrogen-deuterium exchange and mass spectrometry (HDX-MS)
      to study CsgA aggregation, thereby obtaining region-specific information. By
      following time-dependent peptide signal depletion, presumably a result of
      insoluble fibril formation, we acquired sigmoidal profiles that are specific for
      regions (region-specific) of the protein. These signal-depletion profiles not
      only provide an alternative aggregation measurement, but also give insight on
      soluble species in the aggregation. The HDX data present as bimodal isotopic
      distributions, one representing a highly disordered species whereas the other a
      well-structured one. Although the extents of deuterium uptake of the two species
      remain the same with time, the relative abundance of the lower mass, less
      exchanged species increases in a region-specific manner. The same region-specific
      aggregation properties also pertain to different aggregation conditions. Although
      CsgA is an intrinsically disordered protein, within the fibril it is thought to
      consist of five imperfect beta-strand repeating units (labeled R1-R5). We found
      that the exterior repeating units R1 and R5 have higher aggregation propensities
      than do the interior units R2, R3, and R4. We also employed TEM to obtain
      complementary information of the well-structured species. The results provide
      insight on aggregation and a new approach for further application of HDX-MS to
      unravel aggregation mechanisms of amyloid proteins.

PMID- 29056865
TI  - 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose Binds to the N-terminal Metal
      Binding Region to Inhibit Amyloid beta-protein Oligomer and Fibril Formation.
AB  - The early oligomerization of amyloid beta-protein (Abeta) is a crucial step in
      the etiology of Alzheimer's disease (AD), in which soluble and highly neurotoxic
      oligomers are produced and accumulated inside neurons. In search of therapeutic
      solutions for AD treatment and prevention, potent inhibitors that remodel Abeta
      assembly and prevent neurotoxic oligomer formation offer a promising approach. In
      particular, several polyphenolic compounds have shown anti-aggregation properties
      and good efficacy on inhibiting oligomeric amyloid formation. 1,2,3,4,6-penta-O
      galloyl-beta-D-glucopyranose is a large polyphenol that has been shown to be
      effective at inhibiting aggregation of full-length Abeta1-40 and Abeta1-42, but
      has the opposite effect on the C-terminal fragment Abeta25-35. Here, we use a
      combination of ion mobility coupled to mass spectrometry (IMS-MS), transmission
      electron microscopy (TEM) and molecular dynamics (MD) simulations to elucidate
      the inhibitory effect of PGG on aggregation of full-length Abeta1-40 and Abeta1
      42. We show that PGG interacts strongly with these two peptides, especially in
      their N-terminal metal binding regions, and suppresses the formation of Abeta1-40
      tetramer and Abeta1-42 dodecamer. By exploring multiple facets of polyphenol
      amyloid interactions, we provide a molecular basis for the opposing effects of
      PGG on full-length Abeta and its C-terminal fragments.

PMID- 29056866
TI  - Gas-Phase Protein Salt Bridge Stabilities from Collisional Activation and
      Electron Transfer Dissociation.
AB  - The gas phase structures of several proteins have been studied by electron
      transfer dissociation (ETD) with and without prior collisional heating after
      electrospraying these proteins from native-like solutions into a quadrupole ion
      trap mass spectrometer. Without prior collisional heating, we find that ETD
      fragmentation is mostly limited to regions of the protein that are not spanned by
      the salt bridges known to form in solution. When protein ions are collisionally
      heated before ETD, new product ions are observed, and in almost all cases, these
      new ions arise from protein regions that are spanned by the salt bridges.
      Together these results confirm the existence of salt bridges in protein ions and
      demonstrate that a sufficient amount energy is required to disrupt these salt
      bridges in the gas phase. More interestingly, we also show that different salt
      bridges require different collisional activation voltages to be disrupted,
      suggesting that they have variable stabilities in the gas phase. These
      stabilities appear to be influenced by the gas-phase basicities of the involved
      residues and the presence of nearby charged residues. We also find that higher
      collisional activation voltages are needed to enable the formation of new product
      from sites spanned by multiple salt bridges.

PMID- 29056867
TI  - Particle Emissions from Laboratory Activities Involving Carbon Nanotubes.
AB  - This site study was conducted in a chemical laboratory to evaluate nanomaterial
      emissions from 20-30 nm diameter bundles of single-walled carbon nanotubes (CNTs)
      during product development activities. Direct-reading instruments were used to
      monitor the tasks in real time and airborne particles were collected using
      various methods to characterize released nanomaterials using electron microscopy
      and elemental carbon (EC) analyses. CNT clusters and a few high aspect ratio
      particles were identified as being released from some activities. The EC
      concentration at the source of probe sonication was found to be higher than other
      activities including weighing, mixing, centrifugation, coating and cutting.
      Various sampling methods all indicated different levels of CNTs from the
      activities, however, the sonication process was found to release the highest
      amounts of CNTs. It can be cautiously concluded that the task of probe sonication
      possibly released nanomaterials into the laboratory and posed a risk of surface
      contamination. Based on these results, the sonication of CNT suspension should be
      covered or conducted inside a ventilated enclosure with proper filtration or a
      glovebox to minimize the potential of exposure.

PMID- 29056868
TI  - Migration signatures across the decades: Net migration by age in U.S. counties,
      1950-2010.
AB  - BACKGROUND: Migration is the primary population redistribution process in the
      United States. Selective migration by age, race/ethnic group, and spatial
      location governs population integration, affects community and economic
      development, contributes to land use change, and structures service needs.
      OBJECTIVE: Delineate historical net migration patterns by age, race/ethnic, and
      rural-urban dimensions for United States counties. METHODS: Net migration rates
      by age for all US counties are aggregated from 1950-2010, summarized by rural
      urban location and compared to explore differential race/ethnic patterns of age
      specific net migration over time. RESULTS: We identify distinct age-specific net
      migration 'signatures' that are consistent over time within county types, but
      different by rural-urban location and race/ethnic group. There is evidence of
      moderate population deconcentration and diminished racial segregation between
      1990 and 2010. This includes a net outflow of Blacks from large urban core
      counties to suburban and smaller metropolitan counties, continued Hispanic
      deconcentration, and a slowdown in White counterurbanization. CONCLUSIONS: This
      paper contributes to a fuller understanding of the complex patterns of migration
      that have redistributed the U.S. population over the past six decades. It
      documents the variability in county age-specific net migration patterns both
      temporally and spatially, as well as the longitudinal consistency in migration
      signatures among county types and race/ethnic groups.

PMID- 29056869
TI  - Engineered Peptide Repairs Defective Adhesive-Dentin Interface.
AB  - Failure of dental composite restorations is primarily due to recurrent decay at
      the tooth-composite interface. At this interface, the adhesive and its bond with
      dentin is the barrier between the restored tooth and the oral environment. In
      vivo degradation of the bond formed at the adhesive/dentin (a/d) interface
      follows a cascade of events leading to weakening of the composite restoration.
      Here, a peptide-based approach is developed to mineralize deficient dentin
      matrices at the a/d interface. Peptides that have an inherent capacity to self
      assemble on dentin and to induce calcium-phosphate remineralization are anchored
      at the interface. Distribution of adhesive, collagen, and mineral is analyzed
      using micro-Raman spectroscopy and fluorescence microscopy. The analysis
      demonstrates remineralization of the deficient dentin matrices achieved
      throughout the interface with homogeneous distribution of mineral. The peptide
      based remineralization demonstrated here can be an enabling technology to design
      integrated biomaterial-tissue interfaces.

PMID- 29056870
TI  - An Update on Childhood Lead Poisoning.
AB  - Childhood lead poisoning is a multi-faceted, complex condition, which affects not
      only the child's health and well-being, but also the family's housing security,
      economic status, job security, and stress level. This review updates the
      emergency department clinician on the management of childhood lead poisoning.
      Infants and children are at higher risk than adults for lead exposure due to
      their smaller size and proportionately larger dose of ingested toxins, their
      proximity to ground dirt and indoor dust, their energy and curiosity, their oral
      exploratory and pica behaviors, their proportionately larger daily water and milk
      intake, and dietary preferences that differ markedly from those of adults.
      Pediatric health care providers working in the emergency department can provide
      medical management, as well as preventive counseling and guidance, to parents of
      children presenting with evidence of acute or chronic lead poisoning.

PMID- 29056871
TI  - Using Technology to Facilitate Collaboration in Community-Based Participatory
      Research (CBPR).
AB  - This study explores the use of Computer-Supported Collaborative Work (CSCW)
      technologies, by way of a computer-based system called iCohere. This system was
      used to facilitate collaboration conducting Community-Based Participatory
      Research (CBPR). Data was gathered from 13 members of a Community Collaborative
      Board (CCB). Analysis revealed that iCohere served the following functions:
      facilitating communication, providing a depository for information and resource
      sharing, and allowing for remote meeting attendance. Results indicated that while
      iCohere was useful in performing these functions, less expensive technologies had
      the potential to achieve similar goals if properly implemented. Implications for
      future research on CSCW systems and CBPR are discussed.

PMID- 29056872
TI  - Parent Prevention Communication Profiles and Adolescent Substance Use: A Latent
      Profile Analysis and Growth Curve Model.
AB  - This current study identifies distinct parent prevention communication profiles
      and examines whether youth with different parental communication profiles have
      varying substance use trajectories over time. Eleven schools in two rural school
      districts in the Midwestern United States were selected, and 784 students were
      surveyed at three time points from the beginning of 7th grade to the end of 8th
      grade. A series of latent profile analyses were performed to identify discrete
      profiles/subgroups of substance-specific prevention communication (SSPC). The
      results revealed a 4-profile model of SSPC: Active-Open, Passive-Open, Active
      Silent, and Passive-Silent. A growth curve model revealed different rates of
      lifetime substance use depending on the youth's SSPC profile. These findings have
      implications for parenting interventions and tailoring messages for parents to
      fit specific SSPC profiles.

PMID- 29056874
TI  - Systematic inquiry for design of health care information systems: an example of
      elicitation of the patient stakeholder perspective.
AB  - The electronic health record (EHR) has evolved as a tool primarily dictated by
      the needs of health care clinicians and organizations, providing important
      functions supporting day to day work in health care. However, the EHR and
      supporting information systems contain the potential to incorporate patient
      workflows and tasks as well. Integrating patient needs into existing EHR and
      health management systems will require understanding of patients as direct
      stakeholders, necessitating observation and exploration of in situ EHR use by
      patients to envision new opportunities for future systems. In this paper, we
      describe the application of a theoretical framework (Vicente, 1999) to organize
      qualitative data during a multi-stage research study into patient engagement with
      EHRs. By using this method of systematic inquiry, we have more effectively
      elicited patient stakeholder needs and goals to inform the design of future
      health care information systems.

PMID- 29056873
TI  - Characterization of Protein Nanocrystals Based on the Reversibility of
      Crystallization.
AB  - A new approach is described to screen for protein nanocrystals based on the
      reversibility of crystallization. Methods to characterize nanocrystals are in
      strong need to facilitate sample preparation for serial femtosecond X-ray
      nanocrystallography (SFX). SFX enables protein structure determination by
      collecting X-ray diffraction from nano- and microcrystals using a free electron
      laser. This technique is especially valuable for challenging proteins as for
      example membrane proteins and is in general a powerful method to overcome the
      radiation damage problem and to perform time-resolved structure analysis.
      Nanocrystal growth cannot be monitored with common methods used in protein
      crystallography, as the resolution of bright field microscopy is not sufficient.
      A high-performance method to screen for nanocrystals is second order nonlinear
      imaging of chiral crystals (SONICC). However, the high cost prevents its use in
      every laboratory, and some protein nanocrystals may be "invisible" to SONICC. In
      this work using a crystallization robot and a common imaging system precipitation
      comprised of nanocrystals and precipitation caused by aggregated protein can be
      distinguished.

PMID- 29056875
TI  - Housing Status, Psychiatric Symptoms, and Substance Abuse Outcomes Among Sober
      Living House Residents over 18 Months.
AB  - Studies show individuals entering sober living recovery houses (SLHs) make
      significant, sustained improvement on measures of substance abuse problems,
      employment, and arrests. The current study assessed changes in housing status
      among SLH residents over 18 months and the relative influences of housing status
      and psychiatric distress on substance abuse outcomes. Two hundred forty one men
      and 58 women, all age 18 and older, were interviewed within their first week of
      entering 20 SLHs and again at 6-, 12-, and 18-month follow-up. Between entry into
      the SLHs and 18-month follow-up homelessness declined from 16% to 4%, marginal
      housing declined from 66% to 46%, and stable housing increased from 13% to 27%.
      Psychiatric severity was generally mild to moderate in severity, but nevertheless
      showed improvement over the 18-month study period. Multivariate models showed
      worse substance abuse outcomes for residents with higher psychiatric distress and
      unstable housing. Relative to persons with stable housing, those who were
      homeless or marginally housed had worse outcomes and those in SLHs had better
      outcomes. Overall, we conclude that individuals entering SLHs show improvement in
      housing status and psychiatric distress, both of which are associated with better
      substance abuse outcomes.

PMID- 29056876
TI  - Fused Lasso Approach in Regression Coefficients Clustering - Learning Parameter
      Heterogeneity in Data Integration.
AB  - As data sets of related studies become more easily accessible, combining data
      sets of similar studies is often undertaken in practice to achieve a larger
      sample size and higher power. A major challenge arising from data integration
      pertains to data heterogeneity in terms of study population, study design, or
      study coordination. Ignoring such heterogeneity in data analysis may result in
      biased estimation and misleading inference. Traditional techniques of remedy to
      data heterogeneity include the use of interactions and random effects, which are
      inferior to achieving desirable statistical power or providing a meaningful
      interpretation, especially when a large number of smaller data sets are combined.
      In this paper, we propose a regularized fusion method that allows us to identify
      and merge inter-study homogeneous parameter clusters in regression analysis,
      without the use of hypothesis testing approach. Using the fused lasso, we
      establish a computationally efficient procedure to deal with large-scale
      integrated data. Incorporating the estimated parameter ordering in the fused
      lasso facilitates computing speed with no loss of statistical power. We conduct
      extensive simulation studies and provide an application example to demonstrate
      the performance of the new method with a comparison to the conventional methods.

PMID- 29056878
TI  - Building Mobile Apps for Underrepresented Mental Health care Consumers: A
      Grounded Theory Approach.
AB  - Cell phone mobile application ("app") use has risen dramatically within the past
      several years. Many individuals access apps to address mental health issues.
      Unlike individuals from privileged backgrounds, individuals from oppressed
      backgrounds may rely on apps rather than costly mental health treatment. To date,
      very little research has been published evaluating mental health apps'
      effectiveness. This paper focuses on three methods through which grounded theory
      can facilitate app development and evaluation for people underrepresented in
      mental health care. Recommendations are made to advance mobile app technology
      that will help clinicians provide effective treatment, and consumers to realize
      positive treatment outcomes.

PMID- 29056877
TI  - Violence Exposure and Early Substance Use in High-Risk Adolescents.
AB  - This study examines the relationship between violence exposure and early
      substance use as mediated by trauma symptoms. The Assessment of Liability and
      Exposure to Substance Use and Antisocial Behavior Scale was used to assess
      violence exposure at age 10 and substance use by age 12. Mediation analysis
      indicated direct relationships between violence exposure and tobacco/illegal drug
      use and indirect relationships between violence exposure and girls' substance use
      through trauma symptoms. Practitioners should consider violence exposure as a
      risk factor for early substance use in high-risk youths and potential gender
      differences in trauma symptom pathways to early substance use.

PMID- 29056879
TI  - Women living with AIDS in rural Southern India: Perspectives on mental health and
      lay health care worker support.
AB  - In this study, focus groups were conducted with 16 rural Women Living with AIDS
      (WLA) from Andhra Pradesh, India who had previously participated in a clinical
      trial wherein 68 WLA were randomized into either an Accredited Social Health
      Activists (ASHA) - Life (AL) intervention or a Usual Care program. Findings are
      discussed in terms of: a) mental health issues, b) perceived stressors, c)
      individual resources for coping with mental health issues, and d) role of Asha
      support in coping with mental health issues. These findings highlight the
      salience of mental health issues in the lives of WLA and the role played by Asha
      in addressing some of these issues. The discussion section makes a case for
      increased emphasis on mental health care in future community-based interventions
      for this population.

PMID- 29056880
TI  - Supportive Coparenting Relationships as a Haven of Psychological Safety at the
      Transition to Parenthood.
AB  - Guided by research on psychological safety, we used longitudinal survey data from
      a sample of 182 dual-earner male-female couples to examine the role of supportive
      coparenting in mediating relations between adult attachment orientations and
      parenting stress/satisfaction, and further considered whether parenting self
      efficacy moderated relations between supportive coparenting and parenting
      stress/satisfaction. Path analyses using IBM SPSS AMOS 22 and bootstrapping
      techniques indicated that fathers' (but not mothers') perceptions of supportive
      coparenting at 3 months postpartum mediated the associations between their
      attachment anxiety in the third trimester of pregnancy and their parenting stress
      and satisfaction at 9 months postpartum. Additional tests of moderation revealed
      that mothers' perceptions of greater supportive coparenting were associated with
      lower parenting stress only when their parenting self-efficacy was low, but
      fathers' perceptions of greater supportive coparenting were associated with
      greater parenting satisfaction only when their parenting self-efficacy was high.
      Implications and limitations are discussed.

PMID- 29056881
TI  - Rosie the Riveter's Job Market: Advertising for women workers in World War II Los
      Angeles.

PMID- 29056883
TI  - Tunable substrates improve imaging of viruses and cancer proteins.
AB  - Recent breakthroughs in cryo-electron microscopy imaging technology provide an
      unprecedented view of biology at the nanoscale. To complement these technical
      advances, here we demonstrate the use of tunable substrates to streamline the
      isolation of biological entities from human cells. We have tested the capacity of
      tunable microchip devices using a variety of samples including virus assemblies
      and the breast cancer susceptibility protein (BRCA1) produced in cancer cells.
      Overall, microchip applications may shed light on ill-defined clinical issues
      related to molecular disease mechanisms.

PMID- 29056882
TI  - Effects of Testosterone on Benign and Malignant Conditions of the Prostate.
AB  - PURPOSE OF THE REVIEW: This review summarizes the current literature regarding
      the effects of testosterone therapy (TTh) on common disorders of the prostate.
      RECENT FINDINGS: Testosterone therapy has gained credibility over the last
      several decades as a potentially safe co-treatment modality for men with benign
      and malignant prostatic conditions. Our understanding of the effects of
      testosterone on the prostate continues to evolve with ongoing clinical and basic
      science research. Findings of these studies have reinvigorated the debate over
      the effects of testosterone on benign and malignant disorders of the prostate,
      including BPH, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and
      prostate cancer. SUMMARY: Despite the burgeoning body of data claiming the safety
      and efficacy of TTh in common prostatic conditions (including BPH, CP/CPPS, and
      prostate cancer), diligent monitoring, appropriate patient selection, and
      informed consent are critical until more definitive studies are performed.

PMID- 29056884
TI  - In Reference to: "Cost and Utility of Thrombophilia Testing".

PMID- 29056885
TI  - Online Information Search Performance and Search Strategies in a Health Problem
      Solving Scenario.
AB  - Although access to Internet health information can be beneficial, solving complex
      health-related problems online is challenging for many individuals. In this
      study, we investigated the performance of a sample of 60 adults ages 18 to 85
      years in using the Internet to resolve a relatively complex health information
      problem. The impact of age, Internet experience, and cognitive abilities on
      measures of search time, amount of search, and search accuracy was examined, and
      a model of Internet information seeking was developed to guide the
      characterization of participants' search strategies. Internet experience was
      found to have no impact on performance measures. Older participants exhibited
      longer search times and lower amounts of search but similar search accuracy
      performance as their younger counterparts. Overall, greater search accuracy was
      related to an increased amount of search but not to increased search duration and
      was primarily attributable to higher cognitive abilities, such as processing
      speed, reasoning ability, and executive function. There was a tendency for those
      who were younger, had greater Internet experience, and had higher cognitive
      abilities to use a bottom-up (i.e., analytic) search strategy, although use of a
      top-down (i.e., browsing) strategy was not necessarily unsuccessful. Implications
      of the findings for future studies and design interventions are discussed.

PMID- 29056886
TI  - Multifunctional Molecular Beacon Micelles for Intracellular mRNA Imaging and
      Synergistic Therapy in Multidrug-Resistant Cancer Cells.
AB  - Multidrug resistance (MDR) resulting from overexpression of P-glycoprotein (Pgp)
      transporters increases the drug efflux and thereby limits the chemotherapeutic
      efficacy. It is desirable to administer both an MDR1 gene silencer and a
      chemotherapeutic agent in a sequential way to generate a synergistic therapeutic
      effect in multidrug-resistant cancer cells. Herein, we rationally designed an
      anti-MDR1 molecular beacon (MB)-based micelle (a-MBM) nanosystem, which is
      composed of a diacyllipid core densely packed with an MB corona. One of Pgp
      transportable agents, doxorubicin (DOX), was encapsulated in the hydrophobic core
      of the micelle and in the stem sequence of MB. The a-MBM-DOX nanosystem showed an
      efficient self-delivery, enhanced enzymatic stability, excellent target
      selectivity, and high drug-loading capacity. With its relatively high enzymatic
      stability, a-MBM-DOX initially facilitated intracellular MDR1 mRNA imaging to
      distinguish multidrug-resistant and non-multidrug-resistant cells and
      subsequently downregulated the MDR1 gene expression owing to an antisense effect.
      After that, the MB corona was degraded, destroying the micellar nanostructure and
      releasing DOX, which resulted in a high accumulation of DOX in OVCAR8/ADR cells
      and a high chemotherapeutic efficacy owing to successful restoration of drug
      sensitivity. This micelle approach has the potential for both visualizing MDR1
      mRNA and overcoming MDR in a sequential and synergistic way.

PMID- 29056887
TI  - Dietary coconut water vinegar for improvement of obesity-associated inflammation
      in high-fat-diet-treated mice.
AB  - Obesity has become a serious health problem worldwide. Various types of healthy
      food, including vinegar, have been proposed to manage obesity. However, different
      types of vinegar may have different bioactivities. This study was performed to
      evaluate the anti-obesity and anti-inflammatory effects of coconut water vinegar
      on high-fat-diet (HFD)-induced obese mice. Changes in the gut microbiota of the
      mice were also evaluated. To induce obesity, C57/BL mice were continuously fed an
      HFD for 33 weeks. Coconut water vinegar (0.08 and 2 ml/kg body weight) was fed to
      the obese mice from early in week 24 to the end of week 33. Changes in the body
      weight, fat-pad weight, serum lipid profile, expression of adipogenesis-related
      genes and adipokines in the fat pad, expression of inflammatory-related genes,
      and nitric oxide levels in the livers of the untreated and coconut water vinegar
      treated mice were evaluated. Faecal samples from the untreated and coconut water
      vinegar-treated mice (2 ml/kg body weight) were subjected to 16S metagenomic
      analysis to compare their gut microbiota. The oral intake of coconut water
      vinegar significantly (p < 0.05) reduced the body weight, fat-pad weight, and
      serum lipid profile of the HFD-induced obese mice in a dose-dependent manner. We
      also observed up-regulation of adiponectin and down-regulation of sterol
      regulatory element-binding protein-1, retinol-binding protein-4, and resistin
      expression. The coconut water vinegar also reduced HFD-induced inflammation by
      down-regulating nuclear factor-kappaB and inducible nitric oxide synthase
      expression, which consequently reduced the nitric oxide level in the liver.
      Alterations in the gut microbiota due to an increase in the populations of the
      Bacteroides and Akkermansia genera by the coconut water vinegar may have helped
      to overcome the obesity and inflammation caused by the HFD. These results provide
      valuable insights into coconut water vinegar as a potential food ingredient with
      anti-obesity and anti-inflammatory effects.

PMID- 29056888
TI  - Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM):
      a meta-analysis of randomized controlled trials.
AB  - The present study was designed to systematically evaluate the clinical efficacy
      and safety of garlic supplement in the management of type 2 diabetes mellitus
      (T2DM). PubMed, EMBASE, the Cochrane Library, and China National Knowledge
      Internet (CNKI) were searched for relevant randomized controlled trials (RCTs) by
      using the terms garlic and T2DM up to April 2017. The quality of included RCTs
      was assessed by the Cochrane tool of risk of bias, and data of outcomes were
      pooled by REVMAN 5.3. Clinical factors were handled by meta-regression and
      subgroup analysis, and risk of publication bias was explored by inverted funnel
      plots. Nine RCTs involving 768 T2DM patients were included in the meta-analysis,
      and the dose of daily garlic (allicin) supplement ranged from 0.05g to 1.5g. A
      significant reduction in the level of fasting blood glucose in 1-2 weeks [SMD = 
      1.61, 95%CI (-2.89, -0.32)], 3-4 weeks [SMD = -2.87, 95%CI (-4.74, -1.00)], 12
      weeks [SMD = -9.57, 95%CI (-12.39, -6.75)], and 24 weeks [SMD = -21.02, 95%CI (
      32.47, -9.57)] was achieved in favour of the garlic group rather than the control
      group. Significantly decreased fructosamine and glycated hemoglobin (both in 12
      and 24 weeks) were also found in garlic group. Meanwhile, significantly improved
      blood liquids of total cholesterol [SMD = -1.93, 95%CI (-2.98, -0.87), 3-4
      weeks], high density lipoprotein [SMD = -0.41, 95%CI (-0.83, -0.00), 3-4 weeks]
      and low density lipoprotein [SMD = -3.47, 95%CI (-5.76, -1.18), 12 weeks] were
      confirmed after garlic administration. There was no significant difference in
      complications. Current data confirms that garlic supplement plays positive and
      sustained roles in blood glucose, total cholesterol, and high/low density
      lipoprotein regulation in the management of T2DM. Abbreviations: T2DM = type 2
      diabetes mellitus; RCT = randomized controlled trial; SMD = standard mean
      difference; CI = confidence interval; FBG = fasting blood glucose; HbA1c =
      glycated hemoglobin; HDL = high density lipoprotein; LDL = low density
      lipoprotein.

PMID- 29056889
TI  - Saturated fat -a never ending story?
AB  - Science has no clear message regarding health effects of saturated fats, it
      seems. Different RCTs, prospective cohort studies and meta-analysis have led to
      contrasting conclusions. The aim of the present commentary is to discuss some
      possible reasons for an apparently never-ending fat controversy. They are of a
      purely scientific nature, which is important to recognize, but unfortunately hard
      to overcome. First is the placebo problem. In pharmaceutical science, evidence
      based medicine is often synonymous with data on verified medical events from long
      lasting double-blind randomized placebo controlled trials. In nutritional science
      the lack of double-blind design and lack of placebo food generate less conclusive
      data than those achieved in pharmaceutical science. Some scientists may apply the
      same type of scientific criteria used to evaluate the effects of drugs for foods.
      This leaves an impression of insufficient data since in this respect the
      fundamental criteria for evidence based medicine are not present. The next
      scientific problem is the energy balance equation. In contrast to
      pharmaceuticals, nutrients contain energy. An increased intake of one nutrient
      will lead to a decreased intake of another. The effect of change in only one
      nutrient is then difficult to isolate. Lastly, in nutritional science,
      generalizability is difficult compared to pharmaceutical science. Food culture
      interferes with lifestyle and food habits change over time. In conclusion, all
      available knowledge, from molecular experiments to population studies, must be
      taken in to account, to convert scientific data into dietary recommendations.

PMID- 29056890
TI  - Association of raisin consumption with nutrient intake, diet quality, and health
      risk factors in US adults: National Health and Nutrition Examination Survey 2001
      2012.
AB  - Raisins are one of the most commonly consumed dried fruits. Because of their
      unique nutrient profile, raisins may have some distinctive health benefits. The
      purpose of this study was to examine the cross-sectional association between
      raisin consumption and nutrient intake, dietary quality, body weight, and
      metabolic syndrome risk factors in adults. Data from the National Health and
      Nutrition Examination Survey (NHANES), 2001-2012 (n = 29,684) were used. Raisin
      consumers (n = 458, 60% female) were defined as those having any amount of
      raisins during the first 24 h dietary recall. Diet quality was calculated using
      the Healthy Eating Index-2010 (HEI-2010). Covariate (demographic and lifestyle)
      adjusted regression analyses were conducted using appropriate sample weights and
      significance was set at p < 0.01. Raisin consumers had higher intakes of energy
      (9%); higher intakes of 'nutrients of public health concern/shortfall nutrients',
      such as dietary fiber (34%), potassium (16%), magnesium (22%), vitamin C (24%),
      and vitamin E (22%); and lower intakes of 'nutrients to limit', such as added
      sugar (-17%), saturated fat (-15%), and sodium (-10%), than non-consumers. No
      associations were observed for intakes of calcium, iron, vitamin A, vitamin D,
      and folate. Consumers had higher intakes of total fruit (72%), whole fruit
      (111%), vegetables (22%), and whole grains (109%), and had a higher diet quality,
      as indicated by 25% higher total HEI-2010 scores than non-consumers. Compared to
      non-consumers, raisin consumers had a lower body weight (-4.2%), body mass index
      (-5.2%), and waist circumference (-3.8%), were 39% less likely to be overweight
      or obese, and had a 54% reduced risk of metabolic syndrome. In conclusion, raisin
      consumption was associated with better nutrient intake, diet quality, and weight
      parameters, and with lower risk of being obese and having metabolic syndrome in
      US adults.

PMID- 29056891
TI  - Polygala tenuifolia extract inhibits lipid accumulation in 3T3-L1 adipocytes and
      high-fat diet-induced obese mouse model and affects hepatic transcriptome and gut
      microbiota profiles.
AB  - Obesity, the excessive accumulation of lipids in the body, is closely associated
      with many prevalent human disorders. Continued efforts to identify plant extracts
      that exhibit anti-obesity effects have drawn much attention. This study
      investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity
      activity and how PTE may affect liver gene expression and gut microbiota. We used
      3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the
      effects of PTE on lipid accumulation. Next-generation sequencing analysis of
      liver gene expression and gut microbiota profiles following PTE treatment were
      conducted to elucidate possible mechanisms. We found that treatment of fully
      differentiated 3T3-L1 adipocytes with PTE inhibited lipid accumulation in the
      cells through reducing lipid formation and triglyceride content and by increasing
      lipase activity. No cytotoxicity was observed from the PTE treatment. After 5
      weeks of treatment with PTE, the increased body weight, elevated serum
      triglyceride content, and liver steatosis in the high-fat diet-induced obese mice
      were each reduced. Liver transcriptomic analysis revealed that expression of
      genes involved in lipid and cholesterol metabolism was significantly altered. The
      low-grade chronic inflammation of obesity caused by a high-fat diet was also
      decreased after PTE treatment. In addition, treatment with PTE improved the
      relatively low Bacteroidetes/Firmicutes ratio in the gut of high-fat diet-fed
      mice through enrichment of the Proteobacteria population and reduction of the
      Deferribacteres population. In conclusion, treatment with PTE inhibited lipid
      accumulation by inducing the expression of the master transcription factor
      PPARalpha, attenuated the low-grade chronic inflammation of obesity, and also
      altered gut microbiota profiles. These results indicate that PTE has the
      potential to be developed into an anti-obesity food supplement and therapy.
      Abbreviations: Abcg5: ATP-binding cassette subfamily G member 5; ALT: alanine
      aminotransferase; AMPK: adenosine monophosphate-activated protein kinase; AST:
      aspartate aminotransferase; B/F: Bacteroidetes to Firmicutes [ratio]; C/EBPalpha:
      CCAAT/enhancer-binding protein alpha; CR: creatinine; Cyp51: cytochrome P450
      family 51; DMEM: Dulbecco's modified Eagle's medium; Fabp5: fatty acid-binding
      protein 5; FBS: fetal bovine serum; Fdps: farnesyl diphosphate synthase; Glc:
      Glucose; HFD: high-fat diet; GO: gene ontology; HPRT: hypoxanthine guanine
      phosphoribosyl transferase; IBMS: 3-isobutyl-1-methylxanthine; Idi1: isopentenyl
      diphosphate delta isomerase 1; IL-1beta: interleukin-1-beta; Lpin1: phosphatidic
      acid phosphohydrolase; LPS: lipopolysaccharide; Mvd: mevalonate diphosphate
      decarboxylase; ND: normal diet; OTU: operational taxonomic units; Pcsk9:
      proprotein convertase subtilisin/kexin 9; Pctp: phosphatidylcholine transfer
      protein; PPARalpha: peroxisome proliferator-activated receptor alpha; PPARgamma:
      peroxisome proliferator-activated receptor gamma; PTE: Polygala tenuifolia
      extract; Saa1: serum amyloid A1; SD: standard deviation; SEM: standard error of
      the mean; Serpina12: serpin family member 12; Sqle: squalene monooxygenase;
      SREBP1C: sterol regulatory element-binding protein 1C; TCHO: total cholesterol;
      TG: triglyceride.

PMID- 29056892
TI  - Antithrombotic mechanism of polysaccharides in Blackberry (Rubus spp.) seeds.
AB  - The blackberry seed was typically removed as a byproduct and waste from
      blackberry fruits for juices. Developing value-added utilization of berry seeds
      will significantly expand the market for berry products as well as improve
      benefit to berry producers. However, the research on blackberry seed is limited.
      The objective of this paper was to research antithrombotic mechanism of
      polysaccharides in blackberry seeds. Polysaccharides in blackberry seeds were
      extracted, purified and identified by high-performance gel permeation
      chromatography (HPSEC), gas chromatography (GC), fourier transform infrared (FT
      IR) spectrometer and nuclear magnetic resonance spectra (NMR). Anticoagulant
      activities were evaluated in vivo by measuring activated partial thromboplastin
      time (APTT), thrombin time (TT), prothrombin time (PT), fibrinogen (FIB) and
      plasma recalcification time (RRT). Four polysaccharides named BSP-1a, BSP-1b, BSP
      2 and BSP-3 were isolated from Blackberry (Rubus spp.) seeds. The results
      indicated that BSP-1b, BSP-2 and BSP-3 exhibited the anticoagulant activity.
      Therefore, the anti-thrombosis effects of BSP-1b, BSP-2 and BSP-3 were
      investigated in vivo by 6-Keto-PGF1alpha, thromboxane B2 (TXB2), endothelial
      nitric oxide synthase (eNOS), endothelin-1 (ET-1), whole blood viscosity (WBV),
      plasma viscosity (PV), hematocrit (Hct), erythrocyte sedimentation rate (ESR),
      APTT, TT, PT and FIB. The results suggested that BSP-1b, BSP-2 and BSP-3 had the
      inhibition effect on thrombus formation, and the antithrombotic effects were
      associated with the regulation of vascular endothelium active substance,
      activating blood flow and anticoagulation effect.

PMID- 29056893
TI  - The effect of school meals with fatty fish on adolescents' self-reported symptoms
      for mental health: FINS-TEENS - a randomized controlled intervention trial.
AB  - There is a growing body of evidence linking fish consumption and n-3 LCPUFAs to
      mental health. Still, the results from randomized trials with n-3 LCPUFAs show
      conflicting results, and it is possible that the combined effect of several
      nutrients in fish may explain the observed associations. To aim of the present
      study was to investigate if school meals with fatty fish three times per week for
      12 weeks could alter mental health in a sample of typically developing
      adolescents. In the Fish Intervention Studies-TEENS (FINS-TEENS), adolescents
      from eight secondary schools (n=425) in Norway, were randomized to receive school
      meals with fatty fish, meat or n-3 LCPUFA supplements. Mental health was assessed
      with the Strengths and Difficulties Questionnaire (SDQ) and the differences
      between the groups were assessed with linear mixed effect models, unadjusted and
      adjusted for baseline and dietary compliance. The results showed no effects of
      school meals with fatty fish compared to similar meals with meat or n-3 LCPUFAs
      on the adolescents' self-reported symptom scores for mental health. Among
      adolescents scoring above the SDQ cut-offs (high-scorers), the fish- improved
      less than the meat group in the self-reported symptom scores for total
      difficulties- and emotional problems. However, the findings should be regarded as
      preliminary, as the analyses for the high-scorer group were underpowered. In
      conclusion, serving school meals with fatty fish did not alter mental health in a
      typically developing sample of adolescents. It is possible that serving healthy
      school meals with meat is more beneficial than similar meals with fatty fish in
      adolescents scoring high on mental health problems. However, the results should
      be seen as preliminary, as the dietary compliance in the fish group was low and
      the analyses in the high score group underpowered. Thus, further studies should
      investigate the associations between fish consumption and adolescents' mental
      health.

PMID- 29056894
TI  - Magnesium bioavailability from mineral waters with different mineralization
      levels in comparison to bread and a supplement.
AB  - The aim of the present study was to compare the magnesium bioavailability from
      four mineral waters with different types of mineralization (e.g. SO42-, HCO3-,
      calcium) with the magnesium bioavailability from bread and from a magnesium
      supplement. A single-center, randomized, controlled trial with a crossover design
      with 22 healthy men and women was conducted at the Institute of Food Science and
      Human Nutrition, Leibniz University Hannover, Germany. The participants consumed
      the six test products providing 100 mg of magnesium each on six examination days
      with a one-week washout phase in between. The primary outcome variables were the
      24 h urinary magnesium excretion, the 24 h urinary magnesium/creatinine ratio,
      and the area under the curve of serum magnesium levels for 10 h (AUC0-10h). No
      significant differences among groups were observed for either 24 h urinary
      magnesium excretion or 24 h urinary magnesium/creatinine ratio. Likewise,
      statistical group comparisons of AUC0-10h for serum magnesium levels revealed no
      significant differences among the treatment groups. Accordingly, given equivalent
      magnesium availability from all test products, neither SO42- content nor the
      content of HCO3- or of calcium influenced the bioavailability of magnesium. Thus,
      mineral water with higher concentrations of magnesium constitutes a calorie-free
      magnesium source that contributes to optimal magnesium supply.

PMID- 29056895
TI  - The Role of the Baldwin Effect in the Evolution of Human Musicality.
AB  - From the biological perspective human musicality is the term referred to as a set
      of abilities which enable the recognition and production of music. Since music is
      a complex phenomenon which consists of features that represent different stages
      of the evolution of human auditory abilities, the question concerning the
      evolutionary origin of music must focus mainly on music specific properties and
      their possible biological function or functions. What usually differentiates
      music from other forms of human sound expressions is a syntactically organized
      structure based on pitch classes and rhythmic units measured in reference to
      musical pulse. This structure is an auditory (not acoustical) phenomenon, meaning
      that it is a human-specific interpretation of sounds achieved thanks to certain
      characteristics of the nervous system. There is historical and cross-cultural
      diversity of this structure which indicates that learning is an important part of
      the development of human musicality. However, the fact that there is no culture
      without music, the syntax of which is implicitly learned and easily recognizable,
      suggests that human musicality may be an adaptive phenomenon. If the use of
      syntactically organized structure as a communicative phenomenon were adaptive it
      would be only in circumstances in which this structure is recognizable by more
      than one individual. Therefore, there is a problem to explain the adaptive value
      of an ability to recognize a syntactically organized structure that appeared
      accidentally as the result of mutation or recombination in an environment without
      a syntactically organized structure. The possible solution could be explained by
      the Baldwin effect in which a culturally invented trait is transformed into an
      instinctive trait by the means of natural selection. It is proposed that in the
      beginning musical structure was invented and learned thanks to neural plasticity.
      Because structurally organized music appeared adaptive (phenotypic adaptation)
      e.g., as a tool of social consolidation, our predecessors started to spend a lot
      of time and energy on music. In such circumstances, accidentally one individual
      was born with the genetically controlled development of new neural circuitry
      which allowed him or her to learn music faster and with less energy use.

PMID- 29056897
TI  - Kernel-Based Relevance Analysis with Enhanced Interpretability for Detection of
      Brain Activity Patterns.
AB  - We introduce Enhanced Kernel-based Relevance Analysis (EKRA) that aims to support
      the automatic identification of brain activity patterns using
      electroencephalographic recordings. EKRA is a data-driven strategy that
      incorporates two kernel functions to take advantage of the available joint
      information, associating neural responses to a given stimulus condition.
      Regarding this, a Centered Kernel Alignment functional is adjusted to learning
      the linear projection that best discriminates the input feature set, optimizing
      the required free parameters automatically. Our approach is carried out in two
      scenarios: (i) feature selection by computing a relevance vector from extracted
      neural features to facilitating the physiological interpretation of a given brain
      activity task, and (ii) enhanced feature selection to perform an additional
      transformation of relevant features aiming to improve the overall identification
      accuracy. Accordingly, we provide an alternative feature relevance analysis
      strategy that allows improving the system performance while favoring the data
      interpretability. For the validation purpose, EKRA is tested in two well-known
      tasks of brain activity: motor imagery discrimination and epileptic seizure
      detection. The obtained results show that the EKRA approach estimates a relevant
      representation space extracted from the provided supervised information,
      emphasizing the salient input features. As a result, our proposal outperforms the
      state-of-the-art methods regarding brain activity discrimination accuracy with
      the benefit of enhanced physiological interpretation about the task at hand.

PMID- 29056896
TI  - Classical Statistics and Statistical Learning in Imaging Neuroscience.
AB  - Brain-imaging research has predominantly generated insight by means of classical
      statistics, including regression-type analyses and null-hypothesis testing using
      t-test and ANOVA. Throughout recent years, statistical learning methods enjoy
      increasing popularity especially for applications in rich and complex data,
      including cross-validated out-of-sample prediction using pattern classification
      and sparsity-inducing regression. This concept paper discusses the implications
      of inferential justifications and algorithmic methodologies in common data
      analysis scenarios in neuroimaging. It is retraced how classical statistics and
      statistical learning originated from different historical contexts, build on
      different theoretical foundations, make different assumptions, and evaluate
      different outcome metrics to permit differently nuanced conclusions. The present
      considerations should help reduce current confusion between model-driven
      classical hypothesis testing and data-driven learning algorithms for
      investigating the brain with imaging techniques.

PMID- 29056898
TI  - Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic
      Alzheimer's Disease.
AB  - The identification of an early biomarker to diagnose Alzheimer's disease (AD)
      remains a challenge. Neuropathological studies in animal and AD patients have
      shown that mitochondrial dysfunction is a hallmark of the development of the
      disease. Current studies suggest the use of peripheral tissues, like skin
      fibroblasts as a possibility to detect the early pathological alterations present
      in the AD brain. In this context, we studied mitochondrial function properties
      (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged
      match and young healthy patients. We observed that AD fibroblasts presented a
      significant reduction in mitochondrial length with important changes in the
      expression of proteins that control mitochondrial fusion. Moreover, AD
      fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a
      master regulator of mitochondrial fusion, compared to control fibroblasts.
      Complementary to these changes AD fibroblasts showed a dysfunctional
      mitochondrial bioenergetics profile that differentiates these cells from aged
      matched and young patient fibroblasts. Our findings suggest that the human skin
      fibroblasts obtained from AD patients could replicate mitochondrial impairment
      observed in the AD brain. These promising observations suggest that the analysis
      of mitochondrial bioenergetics could represent a promising strategy to develop
      new diagnostic methods in peripheral tissues of AD patients.

PMID- 29056899
TI  - How Wearable Sensors Can Support Parkinson's Disease Diagnosis and Treatment: A
      Systematic Review.
AB  - : Background: Parkinson's disease (PD) is a common and disabling pathology that
      is characterized by both motor and non-motor symptoms and affects millions of
      people worldwide. The disease significantly affects quality of life of those
      affected. Many works in literature discuss the effects of the disease. The most
      promising trends involve sensor devices, which are low cost, low power,
      unobtrusive, and accurate in the measurements, for monitoring and managing the
      pathology. OBJECTIVES: This review focuses on wearable devices for PD
      applications and identifies five main fields: early diagnosis, tremor, body
      motion analysis, motor fluctuations (ON-OFF phases), and home and long-term
      monitoring. The concept is to obtain an overview of the pathology at each stage
      of development, from the beginning of the disease to consider early symptoms,
      during disease progression with analysis of the most common disorders, and
      including management of the most complicated situations (i.e., motor fluctuations
      and long-term remote monitoring). DATA SOURCES: The research was conducted within
      three databases: IEEE Xplore(r), Science Direct(r), and PubMed Central(r),
      between January 2006 and December 2016. STUDY ELIGIBILITY CRITERIA: Since 1,429
      articles were found, accurate definition of the exclusion criteria and selection
      strategy allowed identification of the most relevant papers. RESULTS: Finally,
      136 papers were fully evaluated and included in this review, allowing a wide
      overview of wearable devices for the management of Parkinson's disease.

PMID- 29056901
TI  - Interleukin-10 Attenuates Hypochlorous Acid-Mediated Cytotoxicity to HEI-OC1
      Cochlear Cells.
AB  - Inflammatory reaction plays a crucial role in the pathophysiology of acquired
      hearing loss such as ototoxicity and labyrinthitis. In our earlier work, we
      showed the pivotal role of otic fibrocytes in cochlear inflammation and the
      critical involvement of proinflammatory cytokines in cisplatin ototoxicity. We
      also demonstrated that otic fibrocytes inhibit monocyte chemoattractant protein 1
      (CCL2) upregulation in response to interleukin-10 (IL-10) via heme oxygenase 1
      (HMOX1) signaling, resulting in suppression of cochlear inflammation. However, it
      is still unclear how IL-10 affects inflammation-mediated cochlear injury. Here we
      aim to determine how hypochlorous acid, a model inflammation mediator affects
      cochlear cell viability and how IL-10 affects hypochlorous acid-mediated cochlear
      cell injury. NaOCl, a sodium salt of hypochlorous acid (HOCl) was found to induce
      cytotoxicity of HEI-OC1 cells in a dose-dependent manner. Combination of hydrogen
      peroxide and myeloperoxidase augmented cisplatin cytotoxicity, and this synergism
      was inhibited by N-Acetyl-L-cysteine and ML-171. The rat spiral ligament cell
      line (RSL) appeared to upregulate the antioxidant response element (ARE)
      activities upon exposure to IL-10. RSL cells upregulated the expression of NRF2
      (an ARE ligand) and NR0B2 in response to CoPP (a HMOX1 inducer), but not to ZnPP
      (a HMOX1 inhibitor). Adenovirus-mediated overexpression of NR0B2 was found to
      suppress CCL2 upregulation. IL-10-positive cells appeared in the mouse stria
      vascularis 1 day after intraperitoneal injection of lipopolysaccharide (LPS).
      Five days after injection, IL-10-positive cells were observed in the spiral
      ligament, spiral limbus, spiral ganglia, and suprastrial area, but not in the
      stria vascularis. IL-10R1 appeared to be expressed in the mouse organ of Corti as
      well as HEI-OC1 cells. HEI-OC1 cells upregulated Bcl-xL expression in response to
      IL-10, and IL-10 was shown to attenuate NaOCl-induced cytotoxicity. In addition,
      HEI-OC1 cells upregulated IL-22RA upon exposure to cisplatin, and NaOCl
      cytotoxicity was inhibited by IL-22. Taken together, our findings suggest that
      hypochlorous acid is involved in cochlear injury and that IL-10 potentially
      reduces cochlear injury through not only inhibition of inflammation but also
      enhancement of cochlear cell viability. Further studies are needed to determine
      immunological characteristics of intracochlear IL-10-positive cells and elucidate
      molecular mechanisms involved in the otoprotective activity of IL-10.

PMID- 29056900
TI  - Alzheimer's Disease: From Genetic Variants to the Distinct Pathological
      Mechanisms.
AB  - Being the most common cause of dementia, AD is a polygenic and neurodegenerative
      disease. Complex and multiple factors have been shown to be involved in its
      pathogenesis, of which the genetics play an indispensable role. It is widely
      accepted that discovery of potential genes related to the pathogenesis of AD
      would be of great help for the understanding of neurodegeneration and thus
      further promote molecular diagnosis in clinic settings. Generally, AD could be
      clarified into two types according to the onset age, the early-onset AD (EOAD)
      and the late-onset AD (LOAD). Progresses made by genetic studies on both EOAD and
      LOAD are believed to be essential not only for the revolution of conventional
      ideas but also for the revelation of new pathological mechanisms underlying AD
      pathogenesis. Currently, albeit the genetics of LOAD is much less well-understood
      compared to EOAD due to its complicated and multifactorial essence, Genome-wide
      association studies (GWASs) and next generation sequencing (NGS) approaches have
      identified dozens of novel genes that may provide insight mechanism of LOAD. In
      this review, we analyze functions of the genes and summarize the distinct
      pathological mechanisms of how these genes would be involved in the pathogenesis
      of AD.

PMID- 29056902
TI  - Time Perception and the Experience of Time When Immersed in an Altered Sensory
      Environment.
AB  - The notion that exposure to a monotonous sensory environment could elicit reports
      indicating aberrant subjective experience and altered time perception is the
      impetus for the present report. Research has looked at the influence of exposure
      to such environments on time perception, reporting that the greater the
      environmental variation, the shorter is the time estimation obtained by the
      method of production. Most conditions for creating an altered sensory
      environment, however, have not facilitated an immersive experience, one that
      directly impacts both time perception and subjective experience. In this study,
      we invited our participants to enter a whole-body altered sensory environment for
      a 20-min session, wherein they were asked to relax without falling asleep. The
      session included white-colored illumination of the chamber with eyes closed (5
      min), followed by 10 min of illuminating the room with color, after which a short
      report of subjective experience was collected using a brief questionnaire; this
      was followed by an additional 5 min of immersion in white light with closed eyes.
      The participants were then interviewed regarding their subjective experience,
      including their experience of time within the chamber. Prior to entering the
      chamber, the participants completed a time-production (TP) task. One group of
      participants then repeated the task within the chamber, at the end of the
      session; a second group of participants repeated the task after exiting the
      chamber. We shall report on changes in TP, and present data indicating that when
      produced time is plotted as a function of target duration, using a log-log plot,
      the major influence of sensory environment is on the intercept of the
      psychophysical function. We shall further present data indicating that for those
      participants reporting a marked change in time experience, such as "the sensation
      of time disappeared," their TP data could not be linearized using a log-log plot,
      hence indicating that for these individuals there might be a "break" in the
      psychophysical function.

PMID- 29056903
TI  - Erratum: Aberrant Long-Range Temporal Correlations in Depression Are Attenuated
      after Psychological Treatment.
AB  - [This corrects the article on p. 340 in vol. 11, PMID: 28701943.].

PMID- 29056904
TI  - Early Changes in Alpha Band Power and DMN BOLD Activity in Alzheimer's Disease: A
      Simultaneous Resting State EEG-fMRI Study.
AB  - Simultaneous resting state functional magnetic resonance imaging (rsfMRI)-resting
      state electroencephalography (rsEEG) studies in healthy adults showed robust
      positive associations of signal power in the alpha band with BOLD signal in the
      thalamus, and more heterogeneous associations in cortical default mode network
      (DMN) regions. Negative associations were found in occipital regions. In
      Alzheimer's disease (AD), rsfMRI studies revealed a disruption of the DMN, while
      rsEEG studies consistently reported a reduced power within the alpha band. The
      present study is the first to employ simultaneous rsfMRI-rsEEG in an AD sample,
      investigating the association of alpha band power and BOLD signal, compared to
      healthy controls (HC). We hypothesized to find reduced positive associations in
      DMN regions and reduced negative associations in occipital regions in the AD
      group. Simultaneous resting state fMRI-EEG was recorded in 14 patients with mild
      AD and 14 HC, matched for age and gender. Power within the EEG alpha band (8-12
      Hz, 8-10 Hz, and 10-12 Hz) was computed from occipital electrodes and served as
      regressor in voxel-wise linear regression analyses, to assess the association
      with the BOLD signal. Compared to HC, the AD group showed significantly decreased
      positive associations between BOLD signal and occipital alpha band power in
      clusters in the superior, middle and inferior frontal cortex, inferior temporal
      lobe and thalamus (p < 0.01, uncorr., cluster size >= 50 voxels). This group
      effect was more pronounced in the upper alpha sub-band, compared to the lower
      alpha sub-band. Notably, we observed a high inter-individual heterogeneity.
      Negative associations were only reduced in the lower alpha range in the
      hippocampus, putamen and cerebellum. The present study gives first insights into
      the relationship of resting-state EEG and fMRI characteristics in an AD sample.
      The results suggest that positive associations between alpha band power and BOLD
      signal in numerous regions, including DMN regions, are diminished in AD.

PMID- 29056906
TI  - Random Forest Algorithm for the Classification of Neuroimaging Data in
      Alzheimer's Disease: A Systematic Review.
AB  - Objective: Machine learning classification has been the most important
      computational development in the last years to satisfy the primary need of
      clinicians for automatic early diagnosis and prognosis. Nowadays, Random Forest
      (RF) algorithm has been successfully applied for reducing high dimensional and
      multi-source data in many scientific realms. Our aim was to explore the state of
      the art of the application of RF on single and multi-modal neuroimaging data for
      the prediction of Alzheimer's disease. Methods: A systematic review following
      PRISMA guidelines was conducted on this field of study. In particular, we
      constructed an advanced query using boolean operators as follows: ("random
      forest" OR "random forests") AND neuroimaging AND ("alzheimer's disease" OR
      alzheimer's OR alzheimer) AND (prediction OR classification). The query was then
      searched in four well-known scientific databases: Pubmed, Scopus, Google Scholar
      and Web of Science. Results: Twelve articles-published between the 2007 and 2017
      have been included in this systematic review after a quantitative and qualitative
      selection. The lesson learnt from these works suggest that when RF was applied on
      multi-modal data for prediction of Alzheimer's disease (AD) conversion from the
      Mild Cognitive Impairment (MCI), it produces one of the best accuracies to date.
      Moreover, the RF has important advantages in terms of robustness to overfitting,
      ability to handle highly non-linear data, stability in the presence of outliers
      and opportunity for efficient parallel processing mainly when applied on multi
      modality neuroimaging data, such as, MRI morphometric, diffusion tensor imaging,
      and PET images. Conclusions: We discussed the strengths of RF, considering also
      possible limitations and by encouraging further studies on the comparisons of
      this algorithm with other commonly used classification approaches, particularly
      in the early prediction of the progression from MCI to AD.

PMID- 29056905
TI  - Hyperhomocysteinemia, Suppressed Immunity, and Altered Oxidative Metabolism
      Caused by Pathogenic Microbes in Atherosclerosis and Dementia.
AB  - Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques
      and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor
      for atherosclerosis and dementia, is caused by dysregulation of methionine
      metabolism secondary to deficiency of the allosteric regulator, adenosyl
      methionine. Deficiency of adenosyl methionine results from increased polyamine
      biosynthesis by infected host cells, causing increased activity of ornithine
      decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired
      immune reactions. The down-regulation of oxidative phosphorylation that is
      observed in aging and dementia is attributed to deficiency of thioretinaco
      ozonide oxygen complexed with nicotinamide adenine dinucleotide and phosphate,
      which catalyzes oxidative phosphorylation. Adenosyl methionine biosynthesis is
      dependent upon thioretinaco ozonide and adenosine triphosphate (ATP), and the
      deficiency of adenosyl methionine and impaired immune function in aging are
      attributed to depletion of thioretinaco ozonide from mitochondrial membranes.
      Allyl sulfides and furanonaphthoquinones protect against oxidative stress and
      apoptosis by increasing the endogenous production of hydrogen sulfide and by
      inhibiting electron transfer to the active site of oxidative phosphorylation.
      Diallyl trisulfide and napabucasin inhibit the signaling by the signal transducer
      and activator of transcription 3 (Stat3), potentially enhancing immune function
      by effects on T helper lymphocytes and promotion of apoptosis. Homocysteine
      promotes endothelial dysfunction and apoptosis by the unfolded protein response
      and endoplasmic reticulum stress through activation of the N-methyl D-aspartate
      (NMDA) receptor, causing oxidative stress, calcium influx, apoptosis and
      endothelial dysfunction. The prevention of atherosclerosis and dementia may be
      accomplished by a proposed nutritional metabolic homocysteine-lowering protocol
      which enhances immunity and corrects the altered oxidative metabolism in
      atherosclerosis and dementia.

PMID- 29056907
TI  - Corrigendum: White Matter Changes-Related Gait and Executive Function Deficits:
      Associations with Age and Parkinson's Disease.
AB  - [This corrects the article on p. 213 in vol. 9, PMID: 28713264.].

PMID- 29056908
TI  - Upregulation of HLA Class I Expression on Tumor Cells by the Anti-EGFR Antibody
      Nimotuzumab.
AB  - Defining how epidermal growth factor receptor (EGFR)-targeting therapies
      influence the immune response is essential to increase their clinical efficacy. A
      growing emphasis is being placed on immune regulator genes that govern tumor - T
      cell interactions. Previous studies showed an increase in HLA class I cell
      surface expression in tumor cell lines treated with anti-EGFR agents. In
      particular, earlier studies of the anti-EGFR blocking antibody cetuximab, have
      suggested that increased tumor expression of HLA class I is associated with
      positive clinical response. We investigated the effect of another commercially
      available anti-EGFR antibody nimotuzumab on HLA class I expression in tumor cell
      lines. We observed, for the first time, that nimotuzumab increases HLA class I
      expression and its effect is associated with a coordinated increase in mRNA
      levels of the principal antigen processing and presentation components. Moreover,
      using 7A7 (a specific surrogate antibody against murine EGFR), we obtained
      results suggesting the importance of the increased MHC-I expression induced by
      EGFR-targeted therapies display higher in antitumor immune response. 7A7 therapy
      induced upregulation of tumor MHC-I expression in vivo and tumors treated with
      this antibody display higher susceptibility to CD8+ T cells-mediated lysis. Our
      results represent the first evidence suggesting the importance of the adaptive
      immunity in nimotuzumab-mediated antitumor activity. More experiments should be
      conducted in order to elucidate the relevance of this mechanism in cancer
      patients. This novel immune-related antitumor mechanism mediated by nimotuzumab
      opens new perspectives for its combination with various immunotherapeutic agents
      and cancer vaccines.

PMID- 29056909
TI  - The Dopamine D5 Receptor Is Involved in Working Memory.
AB  - Pharmacological studies indicate that dopamine D1-like receptors (D1 and D5) are
      critically involved in cognitive function. However, the lack of pharmacological
      ligands selective for either the D1 or D5 receptors has made it difficult to
      determine the unique contributions of the D1-like family members. To circumvent
      these pharmacological limitations, we used D5 receptor homozygous (-/-) and
      heterozygous (+/-) knockout mice, to identify the specific role of this receptor
      in higher order cognitive functions. We identified a novel role for D5 receptors
      in the regulation of spatial working memory and temporal order memory function.
      The D5 mutant mice acquired a discrete paired-trial variable-delay T-maze task at
      normal rates. However, both [Formula: see text] and [Formula: see text] mice
      exhibited impaired performance compared to [Formula: see text] littermates when a
      higher burden on working memory faculties was imposed. In a temporal order object
      recognition task, [Formula: see text] exhibited significant memory deficits. No
      D5-dependent differences in locomotor functions and interest in exploring objects
      were evident. Molecular biomarkers of dopaminergic functions within the
      prefrontal cortex (PFC) revealed a selective gene-dose effect on Akt
      phosphorylation at Ser473 with increased levels in [Formula: see text] knockout
      mice. A trend toward reduced levels in CaMKKbeta brain-specific band (64 kDa) in
      [Formula: see text] compared to [Formula: see text] was also evident. These
      findings highlight a previously unidentified role for D5 receptors in working
      memory function and associated molecular signatures within the PFC.

PMID- 29056910
TI  - The Early Awareness and Alert System in Sweden: History and Current Status.
AB  - Introduction: Over the past decades, early awareness and alert (EAA) activities
      and systems have gained importance and become a key early health technology
      assessment (HTA) tool. While a pioneer in HTA, Sweden had no national level EAA
      activities until 2010. We describe the evolution and current status of the
      Swedish EAA System. Methods: This was a historical analysis based on the
      knowledge and experience of the authors supplemented by a targeted review of
      published and gray literature as well as documents relating to EAA activities in
      Sweden. Key milestones and a description of the current state of the Swedish EAA
      System is presented. Results: Initiatives to establish a system for the
      identification and assessment of emerging health technologies in Sweden date back
      to the 1980s. In the 1990s, the Swedish Agency for HTA and Assessment of Social
      Services (SBU) supported the development of EuroScan as one of its founder
      members. In the mid-2000s, an independent regional initiative, driven by the
      Stockholm County Drug and Therapeutics Committee, resulted in the establishment
      of a regional horizon scanning function. By 2009, this work had expanded to a
      collaboration between the four biggest counties in Sweden. The following year it
      was further expanded to the national level and since then the Swedish EAA System
      has been carrying out identification, filtration and prioritization of new
      medicines, early assessment of the prioritized medicines, and dissemination of
      information. In 2015, the EAA System was incorporated into the Swedish national
      process for managed introduction and follow-up of new medicines. Outputs from the
      EAA System are now used to select new medicines for inclusion in this process.
      Conclusions: The Swedish EAA System started as a regional initiative and rapidly
      grew to become a national level activity. An important feature of the system
      today is its complete integration into the national process for managed
      introduction and follow-up of new medicines. The system will continue to evolve
      as a response both to the changing landscape of health innovations and to new
      policy initiatives at the regional, national and international level.

PMID- 29056911
TI  - Diurnal Fluctuations in Plasma Hydrogen Sulfide of the Mice.
AB  - Circadian rhythms are essential in a myriad of physiological processes to
      maintain homeostasis, especially the redox homeostasis. However, little is known
      about whether plasma H2S exhibits the physiological diurnal variation. The
      present study was performed to investigate the diurnal fluctuations of plasma H2S
      and explore the potential mechanisms. We found that the plasma H2S of the
      C57BL/6J mice was significantly higher at 19 o'clock than those at 7 o'clock
      which was not affected by the blood-collecting sequence and the concentrations of
      plasma cysteine (a precursor of H2S). No significant differences in mRNA or
      protein expression of the CSE, CBS, or MPST were observed between 7: 00 and 19:
      00. There were also no significant differences in the CSE and CBS activities,
      while the activities of MPST in tissues were significantly higher at 19 o'clock.
      After treatment with AOAA (a CBS inhibitor) or PPG (a CSE inhibitor) for 14 days,
      plasma H2S concentrations at 19 o'clock were still significantly higher than
      those at 7 o'clock, although they were both significantly decreased as compared
      with controls. Identical findings were also observed in CSE KO mice. We also
      found the plasma H2O2 concentrations were significantly higher at 19 o'clock than
      those at 7 o'clock. However, H2O2 concentrations were significantly decreased at
      19 o'clock than those at 7 o'clock when mice were exposed to continuous light for
      24 h. Meanwhile, the diurnal fluctuations of plasma H2S levels and MPST
      activities in tissues were disappeared. After treatment with DTT for 14 days,
      there was no significant difference in plasma H2O2 concentrations between 7
      o'clock and 19 o'clock. Meanwhile, the diurnal fluctuations of plasma H2S levels
      and MPST activities in tissues were disappeared. Identical findings were also
      observed in SOD2+/- mice. When heart tissues were incubated with increasing
      concentrations of H2O2in vitro, H2O2 could dose-dependently increase the activity
      of MPST within a certain concentration range. In conclusion, our studies revealed
      that plasma H2S concentration and tissue MPST activity exhibited diurnal
      fluctuations. Modulated by plasma H2O2 concentration, changes of MPST activity
      probably led to the diurnal fluctuations of plasma H2S.

PMID- 29056912
TI  - Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its
      Molecular Mechanisms.
AB  - Cardiovascular disease (CVD) has become the leading cause of morbidity and
      mortality worldwide. A well-monitored diet with a sufficient intake of fruits and
      vegetables has been confirmed as a primary prevention of CVD. Plant constituents
      such as flavonoids have been shown to confer healthy benefits. Luteolin (Lut), a
      kind of flavonoid, possesses anti-oxidative, anti-tumor, and anti-inflammatory
      properties. Recent scientific literature has reported the cardiac protective
      effects of Lut in vitro and in vivo. Therefore, the aim of this review is to
      provide an update and detailed overview with cardio-protective molecular
      mechanisms of Lut with a focus on multiple intrinsic and extrinsic effectors. We
      further explore how these mechanisms participate in ischemia/reperfusion (I/R)
      injury, heart failure (HF) and atherosclerosis (AS). A proper understanding of
      the cardiovascular protective effects and the relative mechanisms of Lut may
      provide the possibility of new drug design and development for CVD. With the
      previous studies mainly focused on basic research, we need to advance the
      prospects of its further clinical utilization against CVD, large prospective
      clinical trials of Lut are needed to observe its therapeutic effects on patients
      with I/R injury, HF and AS, especially on the effective therapeutic dosage, and
      safety of long-term administration.

PMID- 29056913
TI  - Anti-Alzheimer's Studies on beta-Sitosterol Isolated from Polygonum hydropiper L.
AB  - The family Polygonaceae is known for its traditional use in the management of
      various neurological disorders including Alzheimer's disease (AD). In search of
      new anti-AD drugs, beta-sitosterol isolated from Polygonum hydropiper was
      subjected to in vitro, in vivo, behavioral and molecular docking studies to
      confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE,
      BChE inhibitory potentials of beta-sitosterol were investigated following
      Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H2O2
      assays. Behavioral studies were performed on a sub-strain of transgenic mice
      using shallow water maze (SWM), Y-maze and balance beam tests. beta-sitosterol
      was tested for in vivo inhibitory potentials against cholinesterase's and free
      radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking
      study was performed to predict the binding mode of beta-sitosterol in the active
      sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo
      cholinesterase inhibitory effects were observed in the beta-sitosterol treated
      groups. beta-sitosterol exhibited an IC50 value of 55 and 50 MUg/ml against AChE
      and BChE respectively. Whereas, the activity of these enzymes were significantly
      low in FC and HC homogenates of transgenic animals. Molecular docking studies
      also support the binding of beta-sitosterol with the target enzyme and further
      support the in vitro and in vivo results. In the antioxidant assays, the IC50
      values were observed as 140, 120, and 280 MUg/ml in the DPPH, ABTS and H2O2
      assays respectively. The free radicals load in the brain tissues was
      significantly declined in the beta-sitosterol treated animals as compared to the
      transgenic-saline treated groups. In the memory assessment and coordination tasks
      including SWM, Y-maze and balance beam tests, beta-sitosterol treated transgenic
      animals showed gradual improvement in working memory, spontaneous alternation
      behavior and motor coordination. These results conclude that beta-sitosterol is a
      potential compound for the management of memory deficit disorders like AD.

PMID- 29056914
TI  - Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti
      Inflammatory Signaling System in Liver.
AB  - Protective mechanisms against drug-induced liver injury are actively being
      searched to identify new therapeutic targets. Among them, the anti-inflammatory N
      acyl ethanolamide (NAE)-peroxisome proliferators activated receptor alpha
      (PPARalpha) system has gained much interest after the identification of its
      protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol
      (APAP), a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it
      is being used as a liver model. In the present study, we have analyzed the impact
      of APAP on the liver NAE-PPARalpha system. A dose-response (0.5-5-10-20 mM) and
      time-course (2-6-24 h) study in human HepG2 cells showed a biphasic response,
      with a decreased PPARalpha expression after 6-h APAP incubation followed by a
      generalized increase of NAE-PPARalpha system-related components (PPARalpha, NAPE
      PLD, and FAAH), including the NAEs oleoyl ethanolamide (OEA) and docosahexaenoyl
      ethanolamide, after a 24-h exposure to APAP. These results were partially
      confirmed in a time-course study of mice exposed to an acute dose of APAP (750
      mg/kg). The gene expression levels of Pparalpha and Faah were decreased after 6 h
      of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as
      well as the liver levels of OEA and palmitoyl ethanolamide, were increased.
      Repeated APAP administration (750 mg/kg/day) up to 4 days also decreased the
      expression levels of PPARalpha and FAAH, and increased the liver levels of NAEs.
      A resting period of 15 days completely restored these impairments. Liver
      immunohistochemistry in a well-characterized human case of APAP hepatotoxicity
      confirmed PPARalpha and FAAH decrements. Histopathological and hepatic damage
      (Cyp2e1, Caspase3, alphaSma, Tnfalpha, and Mcp1)-related alterations observed
      after repeated APAP administration were aggravated in the liver of Pparalpha
      deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARalpha
      signaling system is implicated in liver toxicity after exposure to APAP overdose,
      and may contribute to its recovery through a long-term time-dependent response.

PMID- 29056915
TI  - Short-Duration Maximal and Long-Duration Submaximal Effort Forearm Exercise
      Achieve Elevations in Serum Brain-Derived Neurotrophic Factor.
AB  - Brain-derived neurotrophic factor (BDNF) is a major orchestrator of exercise
      induced brain plasticity and circulating (peripheral) BDNF may have central
      effects. Approximately 99% of circulating BDNF is platelet-bound, and at rest
      ~30% of circulating platelets are stored in the spleen. Interestingly, forearm
      handgrip exercise significantly elevates sympathetic outflow and has been shown
      to induce splenic constriction, suggesting that small muscle mass exercise could
      stand as a viable strategy for increasing circulating BDNF; however, the BDNF
      response to handgrip exercise is currently unknown. Purpose: This study examined
      BDNF and platelet responses to short-duration maximal (ME) and prolonged
      submaximal (SE) effort handgrip exercise. Methods: Healthy males (n = 18; 21.4 +/
      2.1 years, BMI 25.0 +/- 1.0 kg/m2) performed 10 min of ME and 30 min of SE.
      Blood was sampled for the determination of serum BDNF and platelet count at rest
      and during the last minute of exercise. Results: Compared to rest, serum BDNF
      significantly increased during ME (21.2%) and SE (11.2%), which displayed a non
      significant trend toward an intensity-dependent response. Platelets increased in
      an intensity-dependent fashion compared to rest with an 8.0% increase during ME
      and 3.1% during SE, and these responses were significantly correlated with
      diastolic blood pressure responses to handgrip exercise. Further, the amount of
      BDNF per platelet significantly increased compared to rest during ME (13.4%) and
      SE (8.7%). Conclusions: Handgrip exercise evokes significant increases in serum
      BDNF and platelets, implicating splenic constriction as a key mechanism and
      confirming efficacy of this exercise model for elevating circulating BDNF.

PMID- 29056917
TI  - Comprehension of Subject and Object Relative Clauses in a Trilingual Acquisition
      Context.
AB  - Chinese relative clauses (RCs) have word order properties that are distinctly
      rare across languages of the world; such properties provide a good testing ground
      to tease apart predictions regarding the relative complexity of subject and
      object RCs in acquisition and processing. This study considers these special word
      order properties in a multilingual acquisition context, examining how
      Cantonese(L1)-English(L2)-Mandarin(L3) trilingual children process RCs in two
      Chinese languages differing in exposure conditions. Studying in an English
      immersion international school, these trilinguals are also under intensive
      exposure to English. Comparisons of the trilinguals with their monolingual
      counterparts are made with a focus on the directionality of cross-linguistic
      influence. The study considers how various factors such as language exposure,
      structural overlaps in the target languages, typological distance, and language
      dominance can account for the linguistic abilities and vulnerabilities exhibited
      by a group of children in a trilingual acquisition context. Twenty-one trilingual
      5- to 6-year-olds completed tests of subject- and object- RC comprehension in all
      three languages. Twenty-four age-matched Cantonese monolinguals and 24 age
      matched Mandarin monolinguals served as comparison groups. Despite limited
      exposure to Mandarin, the trilinguals performed comparable to the monolinguals.
      Their Cantonese performance uniquely predicts their Mandarin performance,
      suggesting positive transfer from L1 Cantonese to L3 Mandarin. In Cantonese,
      however, despite extensive exposure from birth, the trilinguals comprehended
      object RCs significantly worse than the monolinguals. Error analyses suggested an
      English-based head-initial analysis, implying negative transfer from L2 English
      to L1 Cantonese. Overall, we identified a specific case of bi-directional
      influence between the first and second/third languages. The trilinguals
      experience facilitation in processing Mandarin RCs, because parallels and
      overlaps in both form and function provide a transparent basis for positive
      transfer from L1 Cantonese to L3 Mandarin. On the other hand, they experience
      more difficulty in processing object RCs in Cantonese compared to their
      monolingual peers, because structural overlaps with competing structures from
      English plus intensive exposure to English lead to negative transfer from L2
      English to L1 Cantonese. The findings provide further evidence that head noun
      assignment in object RCs is especially vulnerable in multilingual Cantonese
      children when they are under intensive exposure to English.

PMID- 29056916
TI  - Inhibition of (pro)renin Receptor Contributes to Renoprotective Effects of
      Angiotensin II Type 1 Receptor Blockade in Diabetic Nephropathy.
AB  - Aims: Renal renin-angiotensin system (RAS) plays a pivotal role in the
      development of diabetic nephropathy (DN). Angiotensin II (Ang II) type 1 receptor
      (AT1R) blockade elevates (pro)renin, which may bind to (pro)renin receptor (PRR)
      and exert receptor-mediated, angiotensin-independent profibrotic effects. We
      therefore investigated whether PRR activation leads to the limited anti-fibrotic
      effects of AT1R blockade on DN, and whether PRR inhibition might ameliorate
      progression of DN. Methods: To address the issue, the expression of RAS
      components was tested in different stages of streptozotocin (STZ)-induced
      diabetic rats (6, 12, and 24 weeks) and 6-week AT1R blockade (losartan) treated
      diabetic rats. Using the blocker for PRR, the handle region peptide (HRP) of
      prorenin, the effects of PRR on high glucose or Ang II-induced proliferative and
      profibrotic actions were evaluated by measurement of cell proliferation, matrix
      metalloproteinase-2 (MMP-2) activity, activation of extracellular signal
      regulated kinase 1/2 (ERK1/2) and transforming growth factor-beta1 (TGF-beta1)
      expression in rat mesangial cells (MCs). Results: PRR was downregulated in the
      kidneys of different stages of diabetic rats (6, 12, and 24 weeks). Moreover, 6
      week losartan treatment further suppressed PRR expression via upregulating AT2R,
      and ameliorated diabetic renal injury. HRP inhibited high glucose and Ang II
      induced proliferative and profibrotic effects in MCs through suppressing TGF
      beta1 expression and activating MMP-2. Meanwhile, HRP enhanced losartan's anti
      fibrotic effects through further inhibiting phosphorylation of ERK1/2 and TGF
      beta1 expression. Moreover, the inhibitive effect of HRP on Ang II-induced TGF
      beta1 expression depended on the regulation of PRR expression by AT2R.
      Conclusions: Our findings suggest that inhibition of PRR contributes to
      renoprotection against diabetic nephropathy by AT1R blockade.

PMID- 29056918
TI  - Editorial: The Sensation-Cognition Interface: Impact of Early Sensory Experiences
      on Cognition.

PMID- 29056919
TI  - Analysis of Relations between Spatiotemporal Movement Regulation and Performance
      of Discrete Actions Reveals Functionality in Skilled Climbing.
AB  - In this review of research on climbing expertise, we focus on different measures
      of climbing performance, including spatiotemporal measures related to fluency and
      activity states (i.e., discrete actions), adopted by climbers for achieving
      overall performance goals of getting to the end of a route efficiently and
      safely. Currently, a broad range of variables have been reported, however, many
      of these fail to capture how climbers adapt to a route whilst climbing. We argue
      that spatiotemporal measures should be considered concurrently with evaluation of
      activity states (such as reaching or exploring) in order gain a more
      comprehensive picture of how climbers successfully adapt to a route. Spatial and
      temporal movement measures taken at the hip are a traditional means of assessing
      efficiency of climbing behaviors. More recently, performatory and exploratory
      actions of the limbs have been used in combination with spatiotemporal
      indicators, highlighting the influence of limb states on climbing efficiency and
      skill transfer. However, only a few studies have attempted to combine
      spatiotemporal and activity state measures taken during route climbing. This
      review brings together existing approaches for observing climbing skill at
      performance outcome (i.e., spatiotemporal assessments) and process (i.e., limb
      activity states) levels of analysis. Skill level is associated with a spatially
      efficient route progression and lower levels of immobility. However, more
      difficult hold architecture designs require significantly greater mobility and
      more complex movement patterning to maintain performance. Different forms of
      functional, or goal-supportive, movement variability, including active recovery
      and hold exploration, have been implicated as important adaptations to
      physiological and environmental dynamics that emerge during the act of climbing.
      Indeed, recently it has also been shown that, when climbing on new routes,
      efficient exploration can improve the transfer of skill. This review provides new
      insights into how climbing performance and related actions can be quantified to
      better capture the functional role of movement variability.

PMID- 29056920
TI  - General and Specific Contributions of RAN to Reading and Arithmetic Fluency in
      First Graders: A Longitudinal Latent Variable Approach.
AB  - In the present study, we opted for a longitudinal design and examined rapid
      automatized naming (RAN) performance from two perspectives. In a first step, we
      examined the structure of RAN performance from a general cognitive perspective.
      We investigated whether rapid naming measures (e.g., digit RAN and color RAN)
      reflect a mainly domain-general factor or domain-specific factors. In a second
      step, we examined how the best fitting RAN model was related to reading and
      arithmetic outcomes, assessed several months later. Finally in a third step we
      took a clinical perspective and investigated specific contributions of RAN
      measures to reading and arithmetic outcomes. While RAN has emerged as a promising
      predictor of reading, the relationship between RAN and arithmetic has been less
      examined in the past. Hundred and twenty-two first graders completed seven RAN
      tasks, each comprising visually familiar stimuli such as digits, vowels,
      consonants, dice, finger-numeral configurations, objects, and colors. Four months
      later the same children completed a range of reading and arithmetic tasks. From a
      general descriptive perspective, structural equation modeling supports a one
      dimensional RAN factor in 6- to -7-year-old children. However, from a clinical
      perspective, our findings emphasize the specific contributions of RANs.
      Interestingly, alphanumeric RANs (i.e., vowel RAN) were most promising when
      predicting reading skills and number-specific RANs (i.e., finger-numeral
      configuration RAN) were most promising when predicting arithmetic fluency. The
      implications for clinical and educational practices will be discussed.

PMID- 29056921
TI  - EEG Differentiation Analysis and Stimulus Set Meaningfulness.
AB  - A set of images can be considered as meaningfully different for an observer if
      they can be distinguished phenomenally from one another. Each phenomenal
      difference must be supported by some neurophysiological differences.
      Differentiation analysis aims to quantify neurophysiological differentiation
      evoked by a given set of stimuli to assess its meaningfulness to the individual
      observer. As a proof of concept using high-density EEG, we show increased
      neurophysiological differentiation for a set of natural, meaningfully different
      images in contrast to another set of artificially generated, meaninglessly
      different images in nine participants. Stimulus-evoked neurophysiological
      differentiation (over 257 channels, 800 ms) was systematically greater for
      meaningful vs. meaningless stimulus categories both at the group level and for
      individual subjects. Spatial breakdown showed a central-posterior peak of
      differentiation, consistent with the visual nature of the stimulus sets. Temporal
      breakdown revealed an early peak of differentiation around 110 ms, prominent in
      the central-posterior region; and a later, longer-lasting peak at 300-500 ms that
      was spatially more distributed. The early peak of differentiation was not
      accompanied by changes in mean ERP amplitude, whereas the later peak was
      associated with a higher amplitude ERP for meaningful images. An ERP component
      similar to visual-awareness-negativity occurred during the nadir of
      differentiation across all image types. Control stimulus sets and further
      analysis indicate that changes in neurophysiological differentiation between
      meaningful and meaningless stimulus sets could not be accounted for by spatial
      properties of the stimuli or by stimulus novelty and predictability.

PMID- 29056922
TI  - What Is Your Faction? Multidimensional Evidence for the Divergent Series As the
      Basis for a New Model of Personality and Work Life.
AB  - Introduction: The successful "Divergent" sci-fi trilogy by writer Veronica Roth
      portrays a dystopian and post-apocalyptic society where the population is divided
      into five groups called "Factions," each with a specific social role and
      associated to a specific set of psychological traits. Though fictional, such
      typology is compelling and may provide a significant contribution to personality
      studies. Objectives: To investigate the accuracy of the classification of
      psychological and sociocultural traits into five Factions as described in
      Divergent and their potential practical usefulness for understanding work life
      choices and experiences in organizations. Method: A total of 217 Brazilian adult
      men and women of various ages, socioeconomic status and ethnicities were
      submitted to measures of several psychological and sociocultural variables, as
      well as of how strongly they supposedly manifest each Faction. The resulting
      dataset was studied using Smallest Space Analysis (SSA) and Facet Theory.
      Results: The Factions were shown not only to be associated to psychological
      variables in ways consistent with the descriptions from Divergent, but also to be
      related to specific aspects of one's work life in organizations. Conclusion: The
      five Factions conceived by Roth appear to constitute an original set of
      constructs that are psychologically valid and, at the same time, of practical use
      in predicting work life choices and experiences. This justifies engaging in
      future empirical and theoretical work toward a new scientific model of potential
      practical value.

PMID- 29056923
TI  - Corrigendum: The Story So Far: How Embodied Cognition Advances Our Understanding
      of Meaning-Making.
AB  - [This corrects the article on p. 1315 in vol. 8, PMID: 28824497.].

PMID- 29056924
TI  - Corrigendum: How Upward Moral Comparison Influences Prosocial Behavioral
      Intention: Examining the Mediating Role of Guilt and the Moderating Role of Moral
      Identity.
AB  - [This corrects the article on p. 1554 in vol. 8, PMID: 28959221.].

PMID- 29056926
TI  - Highly Diversified Pandoraea pulmonicola Population during Chronic Colonization
      in Cystic Fibrosis.
AB  - Several environmental bacteria are considered as opportunistic pathogens in
      cystic fibrosis (CF) and are able to persistently colonize the CF respiratory
      tract (CFRT). Beside Pseudomonas aeruginosa and Burkholderia cepacia complex,
      Pandoraea spp. are defined as pathogenic. During chronic colonization, adaptive
      evolution and diversified population have been demonstrated, notably for P.
      aeruginosa. However, the persistence of Pandoraea in the CFRT remains largely
      unexplored. We studied genomic and phenotypic traits of Pandoraea pulmonicola
      isolates successively recovered from the airways of a single CF patient and
      relate the results to qualitative and quantitative evolution of other cultivable
      pathogens and to patient clinical status. A total of 31 isolates recovered from
      18 sputum samples over a 7-year period in a single CF patient were studied.
      Genome dynamics was assessed by pulsed-field gel electrophoresis, ERIC-PCR
      fingerprinting and 16S rRNA gene PCR-temporal temperature gel electrophoresis.
      Phenotypic features included antimicrobial susceptibility, motility, biofilm
      production, and virulence in Caenorhabditis elegans model. Variability was
      observed for all the characteristics studied leading to highly diversified
      patterns (24 patterns) for the 31 clonally related isolates. Some of these
      modifications, mainly genomic events were concomitantly observed with CFRT
      microbiota composition shifts and with severe exacerbations. The diversity of P.
      pulmonicola population studied, observed for isolates recovered from successive
      samples but also within a sample suggested that existence of a diversified
      population may represent a patho-adaptive strategy for host persistence in the
      heterogeneous and fluctuating CFRT environment.

PMID- 29056925
TI  - Host-Microbiota Mutualism in Metabolic Diseases.
AB  - The intestinal microbiota is a plastic ecosystem that is shaped by environmental
      and genetic factors, interacting with virtually all tissues of the host. Many
      signals result from the interplay between the microbiota with its mammalian
      symbiont that can lead to altered metabolism. Disruptions in the microbial
      composition are associated with a number of comorbidities linked to the metabolic
      syndrome. Promoting the niche expansion of beneficial bacteria through diet and
      supplements can improve metabolic disorders. Reintroducing bacteria through
      probiotic treatment or fecal transplant is a strategy under active investigation
      for multiple pathological conditions. Here, we review the recent knowledge of
      microbiota's contribution to host pathology, the modulation of the microbiota by
      dietary habits, and the potential therapeutic benefits of reshaping the gut
      bacterial landscape in context of metabolic disorders such as obesity.

PMID- 29056927
TI  - Methicillin Resistant Staphylococcus aureus Transmission in a Ghanaian Burn Unit:
      The Importance of Active Surveillance in Resource-Limited Settings.
AB  - Objectives:Staphylococcus aureus infections in burn patients can lead to serious
      complications and death. The frequency of S. aureus infection is high in low- and
      middle-income countries presumably due to limited resources, misuse of
      antibiotics and poor infection control. The objective of the present study was to
      apply population genomics to precisely define, for the first time, the
      transmission of antibiotic resistant S. aureus in a resource-limited setting in
      sub-Saharan Africa. Methods:Staphylococcus aureus surveillance was performed
      amongst burn patients and healthcare workers during a 7-months survey within the
      burn unit of the Korle Bu Teaching Hospital in Ghana. Results: Sixty-six S.
      aureus isolates (59 colonizing and 7 clinical) were obtained from 31 patients and
      10 healthcare workers. Twenty-one of these isolates were ST250-IV methicillin
      resistant S. aureus (MRSA). Notably, 25 (81%) of the 31 patients carried or were
      infected with S. aureus within 24 h of admission. Genome comparisons revealed six
      distinct S. aureus clones circulating in the burn unit, and demonstrated multiple
      transmission events between patients and healthcare workers. Further, the
      collected S. aureus isolates exhibited a wide range of genotypic resistances to
      antibiotics, including trimethoprim (21%), aminoglycosides (33%), oxacillin
      (33%), chloramphenicol (50%), tetracycline (59%) and fluoroquinolones (100%).
      Conclusion: Population genomics uncovered multiple transmission events of S.
      aureus, especially MRSA, within the investigated burn unit. Our findings
      highlight lapses in infection control and prevention, and underscore the great
      importance of active surveillance to protect burn victims against multi-drug
      resistant pathogens in resource-limited settings.

PMID- 29056928
TI  - Denitrification and Biodiversity of Denitrifiers in a High-Mountain Mediterranean
      Lake.
AB  - Wet deposition of reactive nitrogen (Nr) species is considered a main factor
      contributing to N inputs, of which nitrate ([Formula: see text]) is usually the
      major component in high-mountain lakes. The microbial group of denitrifiers are
      largely responsible for reduction of nitrate to molecular dinitrogen (N2) in
      terrestrial and aquatic ecosystems, but the role of denitrification in removal of
      contaminant nitrates in high-mountain lakes is not well understood. We have used
      the oligotrophic, high-altitude La Caldera lake in the Sierra Nevada range
      (Spain) as a model to study the role of denitrification in nitrate removal.
      Dissolved inorganic Nr concentration in the water column of la Caldera, mainly
      nitrate, decreased over the ice-free season which was not associated with growth
      of microbial plankton or variations in the ultraviolet radiation. Denitrification
      activity, estimated as nitrous oxide (N2O) production, was measured in the water
      column and in sediments of the lake, and had maximal values in the month of
      August. Relative abundance of denitrifying bacteria in sediments was studied by
      quantitative polymerase chain reaction of the 16S rRNA and the two
      phylogenetically distinct clades nosZI and nosZII genes encoding nitrous oxide
      reductases. Diversity of denitrifiers in sediments was assessed using a culture
      dependent approach and after the construction of clone libraries employing the
      nosZI gene as a molecular marker. In addition to genera Polymorphum, Paracoccus,
      Azospirillum, Pseudomonas, Hyphomicrobium, Thauera, and Methylophaga, which were
      present in the clone libraries, Arthrobacter, Burkholderia, and Rhizobium were
      also detected in culture media that were not found in the clone libraries.
      Analysis of biological activities involved in the C, N, P, and S cycles from
      sediments revealed that nitrate was not a limiting nutrient in the lake, allowed
      N2O production and determined denitrifiers' community structure. All these
      results indicate that denitrification could be a major biochemical process
      responsible for the N losses that occur in La Caldera lake.

PMID- 29056929
TI  - Evaluation on Infectivity of Babesia microti to Domestic Animals and Ticks
      Outside the Ixodes Genus.
AB  - Babesiosis caused by Babesia microti parasite is an emerging tick borne zoonotic
      disease that was confirmed recently in China. To understand the epidemiology
      characteristics of this emerging disease, infectivity of B. microti to domestic
      animals and ticks outside the genus Ixodes was evaluated in this study. Different
      domestic animals, chick, pig, goat, dog and the reference host rat were
      experimentally inoculated with B. microti-infected erythrocytes and the parasite
      infection was monitored daily by blood smear observation, real-time PCR
      detection, nested-PCR and special antibody responses during 55 days period. The
      results showed that rats infected with B. microti showed a typical sustained
      infection with strongly antibody responses; however, both goats and dogs infected
      with B. microti only showed transient antibody responses and the parasite was not
      found by blood smear observation or PCR; neither the parasite nor the special
      antibodies were detected in experimental chicks and pigs. On the other hand, the
      present study also experimentally investigated the infectivity of B. microti to
      Rhipicephalus haemaphysaloides, Haemaphysalis longicornis, and Hyalomma asiaticum
      three species of ticks outside the genus Ixodes and the transmission experiment
      of B. microti between H. longicornis ticks and mice. Results showed that B.
      microti can be detected in the nymph and adult of these species after molting
      from engorged tick fed on infected mice, but the parasite was not detected in
      larvae hatching from eggs of engorged female tick fed on the infected mice.
      Transmission of B. microti to mice by infected H. longicornis nymphs was
      confirmed. These results indicated that these domestic animals do not have
      reservoir competence for B. microti, however, three species of ticks out of the
      genus Ixodes, common in China were successfully infected by B. microti, with H.
      longicornis showing the potential of transmitting the parasite to the vertebrate
      host.

PMID- 29056930
TI  - High-Altitude Living Shapes the Skin Microbiome in Humans and Pigs.
AB  - While the skin microbiome has been shown to play important roles in health and
      disease in several species, the effects of altitude on the skin microbiome and
      how high-altitude skin microbiomes may be associated with health and disease
      states remains largely unknown. Using 16S rRNA marker gene sequencing, we
      characterized the skin microbiomes of people from two racial groups (the Tibetans
      and the Hans) and of three local pig breeds (Tibetan pig, Rongchang pig, and
      Qingyu pig) at high and low altitudes. The skin microbial communities of low
      altitude pigs and humans were distinct from those of high-altitude pigs and
      humans, with five bacterial taxa (Arthrobacter, Paenibacillus, Carnobacterium,
      and two unclassified genera in families Cellulomonadaceae and Xanthomonadaceae)
      consistently enriched in both pigs and humans at high altitude. Alpha diversity
      was also significantly lower in skin samples collected from individuals living at
      high altitude compared to individuals at low altitude. Several of the taxa unique
      to high-altitude humans and pigs are known extremophiles adapted to harsh
      environments such as those found at high altitude. Altogether our data reveal
      that altitude has a significant effect on the skin microbiome of pigs and humans.

PMID- 29056931
TI  - Myriophyllum aquaticum Constructed Wetland Effectively Removes Nitrogen in Swine
      Wastewater.
AB  - Removal of nitrogen (N) is a critical aspect in the functioning of constructed
      wetlands (CWs), and the N treatment in CWs depends largely on the presence and
      activity of macrophytes and microorganisms. However, the effects of plants on
      microorganisms responsible for N removal are poorly understood. In this study, a
      three-stage surface flow CW was constructed in a pilot-scale within monospecies
      stands of Myriophyllum aquaticum to treat swine wastewater. Steady-state
      conditions were achieved throughout the 600-day operating period, and a high
      (98.3%) average ammonia removal efficiency under a N loading rate of 9 kg ha-1 d
      1 was observed. To determine whether this high efficiency was associated with the
      performance of active microbes, the abundance, structure, and interactions of
      microbial community were compared in the unvegetated and vegetated samples. Real
      time quantitative polymerase chain reactions showed the abundances of nitrifying
      genes (archaeal and bacterial amoA) and denitrifying genes (nirS, nirK, and nosZ)
      were increased significantly by M. aquaticum in the sediments, and the strongest
      effects were observed for the archaeal amoA (218-fold) and nirS genes (4620
      fold). High-throughput sequencing of microbial 16S rRNA gene amplicons showed
      that M. aquaticum greatly changed the microbial community, and ammonium oxidizers
      (Nitrosospira and Nitrososphaera), nitrite-oxidizing bacteria (Nitrospira), and
      abundant denitrifiers including Rhodoplanes, Bradyrhizobium, and Hyphomicrobium,
      were enriched significantly in the sediments. The results of a canonical
      correspondence analysis and Mantle tests indicated that M. aquaticum may shift
      the sediment microbial community by changing the sediment chemical properties.
      The enriched nitrifiers and denitrifiers were distributed widely in the vegetated
      sediments, showing positive ecological associations among themselves and other
      bacteria based on phylogenetic molecular ecological networks.

PMID- 29056932
TI  - Pathogenicity of Human ST23 Streptococcus agalactiae to Fish and Genomic
      Comparison of Pathogenic and Non-pathogenic Isolates.
AB  - Streptococcus agalactiae, or Group B Streptococcus (GBS), is a major pathogen
      causing neonatal sepsis and meningitis, bovine mastitis, and fish
      meningoencephalitis. CC23, including its namesake ST23, is not only the
      predominant GBS strain derived from human and cattle, but also can infect a
      variety of homeothermic and poikilothermic species. However, it has never been
      characterized in fish. This study aimed to determine the pathogenicity of ST23
      GBS to fish and explore the mechanisms causing the difference in the
      pathogenicity of ST23 GBS based on the genome analysis. Infection of tilapia with
      10 human-derived ST23 GBS isolates caused tissue damage and the distribution of
      pathogens within tissues. The mortality rate of infection was ranged from 76 to
      100%, and it was shown that the mortality rate caused by only three human
      isolates had statistically significant difference compared with fish-derived ST7
      strain (P < 0.05), whereas the mortality caused by other seven human isolates did
      not show significant difference compared with fish-derived ST7 strain. The genome
      comparison and prophage analysis showed that the major genome difference between
      virulent and non-virulent ST23 GBS was attributed to the different prophage
      sequences. The prophage in the P1 region contained about 43% GC and encoded 28-39
      proteins, which can mediate the acquisition of YafQ/DinJ structure for GBS by
      phage recombination. YafQ/DinJ belongs to one of the bacterial toxin-antitoxin
      (TA) systems and allows cells to cope with stress. The ST23 GBS strains carrying
      this prophage were not pathogenic to tilapia, but the strains without the
      prophage or carrying the pophage that had gene mutation or deletion, especially
      the deletion of YafQ/DinJ structure, were highly pathogenic to tilapia. In
      conclusion, human ST23 GBS is highly pathogenic to fish, which may be related to
      the phage recombination.

PMID- 29056934
TI  - Corrigendum: Resolving the abundance and air-sea fluxes of airborne
      microorganisms in the North Atlantic Ocean.
AB  - [This corrects the article on p. 557 in vol. 5, PMID: 25400625.].

PMID- 29056933
TI  - Linking the Gut Microbial Ecosystem with the Environment: Does Gut Health Depend
      on Where We Live?
AB  - Global comparisons reveal a decrease in gut microbiota diversity attributed to
      Western diets, lifestyle practices such as caesarian section, antibiotic use and
      formula-feeding of infants, and sanitation of the living environment. While gut
      microbial diversity is decreasing, the prevalence of chronic inflammatory
      diseases such as inflammatory bowel disease, diabetes, obesity, allergies and
      asthma is on the rise in Westernized societies. Since the immune system
      development is influenced by microbial components, early microbial colonization
      may be a key factor in determining disease susceptibility patterns later in life.
      Evidence indicates that the gut microbiota is vertically transmitted from the
      mother and this affects offspring immunity. However, the role of the external
      environment in gut microbiome and immune development is poorly understood.
      Studies show that growing up in microbe-rich environments, such as traditional
      farms, can have protective health effects on children. These health-effects may
      be ablated due to changes in the human lifestyle, diet, living environment and
      environmental biodiversity as a result of urbanization. Importantly, if early
      life exposure to environmental microbes increases gut microbiota diversity by
      influencing patterns of gut microbial assembly, then soil biodiversity loss due
      to land-use changes such as urbanization could be a public health threat. Here,
      we summarize key questions in environmental health research and discuss some of
      the challenges that have hindered progress toward a better understanding of the
      role of the environment on gut microbiome development.

PMID- 29056935
TI  - The Atypical Receptor CCRL2 (C-C Chemokine Receptor-Like 2) Does Not Act As a
      Decoy Receptor in Endothelial Cells.
AB  - C-C chemokine receptor-like 2 (CCRL2) is a non-signaling seven-transmembrane
      domain (7-TMD) receptor related to the atypical chemokine receptor (ACKR) family.
      ACKRs bind chemokines but do not activate G protein-dependent signaling or cell
      functions. ACKRs were shown to regulate immune functions in vivo by their ability
      to scavenge chemokines from the local environment. This study was performed to
      investigate whether CCRL2 shares two of the main characteristics of ACKRs, namely
      the ability to internalize and scavenge the ligands. Cell membrane analysis of
      CCRL2-transfected cells revealed a weak, constitutive, ligand-independent
      internalization, and recycling of CCRL2, with a kinetics that was slower than
      those observed with ACKR3, a prototypic ACKR, or other chemotactic signaling
      receptors [i.e., chemokine-like receptor 1 and C-X-C motif chemokine receptor 2].
      Intracellularly, CCRL2 colocalized with early endosome antigen 1-positive and
      Rab5-positive vesicles and with recycling compartments mainly characterized by
      Rab11-positive vesicles. CCRL2-transfected cells and activated mouse blood
      endothelial cells, that endogenously express CCRL2, were used to investigate the
      scavenging ability of CCRL2. These experiments confirmed the ability of CCRL2 to
      bind chemerin, the only recognized ligand, but excluded the ability of CCRL2 to
      perform scavenging. Collectively, these results identify unique functional
      properties for this member of the non-signaling 7-TMD receptor family.

PMID- 29056937
TI  - CD14+ Cells with the Phenotype of Infiltrated Monocytes Consist of Distinct
      Populations Characterized by Anti-inflammatory as well as Pro-inflammatory
      Activity in Gouty Arthritis.
AB  - It has been suggested that inflammasome-mediated IL-1beta production in monocytic
      cells is responsible for the acute inflammatory response in gouty arthritis.
      However, phenotypical and functional analyses of monocytes during gouty arthritis
      have yet to be conducted. Therefore, we investigated the characteristics of
      monocytes/macrophages in the synovial fluid cells of patients with acute gout.
      The number and frequency of monocytes/macrophages in the synovial fluid
      mononuclear cells (SFMCs) of patients was examined. The expression of markers for
      monocyte recruitment and tissue-resident macrophages, the production of pro
      inflammatory and anti-inflammatory cytokines, and phagocytosis were analyzed in
      the monocytes/macrophages of patients with acute gout attacks. The number and
      frequency of CD14+CD3-CD19-CD56- monocytes/macrophages was markedly increased in
      the SFMCs of patients with gout compared to those of patients with rheumatoid
      arthritis (RA). CD14+ cells showed the phenotypes of infiltrated monocytes rather
      than tissue-resident macrophages, characterized by a high expression of CCR2,
      MRP8, and MRP14, but a low expression of MERTK and 25F9. These cells had the
      capacity to produce pro-inflammatory cytokines such as TNF-alpha and IL-1beta
      after stimulation with lipopolysaccharides. In addition, anti-inflammatory
      features, including CD163 expression and IL-10 production from CD14+ cells, were
      significantly higher in patients with gout than in those with RA. CD14+ cells
      with phenotype of M2 macrophages had high phagocytic activity for monosodium
      urate crystals. Thus, our results indicate that monocytes/macrophages from
      patients with gout have the phenotype of infiltrated monocytes, and these cells
      consist of different populations characterized by anti-inflammatory activities as
      well as pro-inflammatory functions.

PMID- 29056938
TI  - The Small Rho GTPases Rac1 and Rac2 Are Important for T-Cell Independent Antigen
      Responses and for Suppressing Switching to IgG2b in Mice.
AB  - The Rho GTPases Cdc42, Rac1, and Rac2 coordinate receptor signaling to cell
      adhesion, migration, and proliferation. Deletion of Rac1 and Rac2 early during B
      cell development leads to failure in B cell entry into the splenic white pulp.
      Here, we sought to understand the role of Rac1 and Rac2 in B cell functionality
      and during the humoral antibody response. To circumvent the migratory deficiency
      of B cells lacking both Rac1 and Rac2, we took the approach to inducibly delete
      Rac1 in Rac2-/- B cells in the spleen (Rac1BRac2-/- B cells). Rac1BRac2-/- mice
      had normal differentiation of splenic B cell populations, except for a reduction
      in marginal zone B cells. Rac1BRac2-/- B cells showed normal spreading response
      on antibody-coated layers, while both Rac2-/- and Rac1BRac2-/- B cells had
      reduced homotypic adhesion and decreased proliferative response when compared to
      wild-type B cells. Upon challenge with the T-cell-independent antigen TNP
      conjugated lipopolysaccharide, Rac1BRac2-/- mice showed reduced antibody
      response. In contrast, in response to the T-cell-dependent antigen sheep red
      blood cells, Rac1BRac2-/- mice had increased serum titers of IgG1 and IgG2b.
      During in vitro Ig class switching, Rac1BRac2-/- B cells had elevated germline
      gamma2b transcripts leading to increased Ig class switching to IgG2b. Our data
      suggest that Rac1 and Rac2 serve an important role in regulation of the B cell
      humoral immune response and in suppressing Ig class switching to IgG2b.

PMID- 29056939
TI  - Developmental Changes in Time and Space Promote Evolutionary Diversification of
      Flowers: A Case Study in Dipsacoideae.
AB  - Diversification in flower shape and function is triggered by the high plasticity
      of flower meristems. Minute changes in space and time can profoundly affect the
      formation of adult structures. Dipsacoideae provides an excellent model system to
      investigate the evolutionary aspects of temporal and spatial changes in flower
      development due to its small size, the resolved phylogenetic framework, and
      significant diversity of perianth form and merosity. In the present study, we
      investigated the sequence of floral organ initiation and quantified the
      interactions between flower meristem expansion and petal primordium size in eight
      species representing two major clades of Dipsacoideae. Our quantitative study
      indicates the plasticity of the flower meristem for the regulation of pentamery
      either due to a decrease in petal primordium size (Scabiosa) or an increase in
      flower meristem size (Pterocephalus and Lomelosia) compared to tetramerous
      flowers. According to our results, temporal shifts of organ initiation during
      flower evolution contribute to the morphological diversity of perianth. Sepal
      reduction in members of the Dipknautids is paralleled by a delay in sepal
      initiation. The multiplication of sepals in Lomelosia and Pterocephalus is
      correlated with an extension of initiation time. Some heterochronies in early
      development do not affect adult morphology. The effects of a temporal change in
      early development can be enhanced, reduced, or eliminated by later changes of the
      growth rate during development. Our results confirm the hypothesis that the
      interaction between timing and space plays an important role for evolutionary
      diversification of flowers.

PMID- 29056936
TI  - Are Evolution and the Intracellular Innate Immune System Key Determinants in HIV
      Transmission?
AB  - HIV-1 is the single most important sexually transmitted disease in humans from a
      global health perspective. Among human lentiviruses, HIV-1 M group has uniquely
      achieved pandemic levels of human-to-human transmission. The requirement to
      transmit between hosts likely provides the strongest selective forces on a virus,
      as without transmission, there can be no new infections within a host population.
      Our perspective is that evolution of all of the virus-host interactions, which
      are inherited and perpetuated from host-to-host, must be consistent with
      transmission. For example, CXCR4 use, which often evolves late in infection, does
      not favor transmission and is therefore lost when a virus transmits to a new
      host. Thus, transmission inevitably influences all aspects of virus biology,
      including interactions with the innate immune system, and dictates the biological
      niche in which the virus exists in the host. A viable viral niche typically does
      not select features that disfavor transmission. The innate immune response
      represents a significant selective pressure during the transmission process. In
      fact, all viruses must antagonize and/or evade the mechanisms of the host innate
      and adaptive immune systems that they encounter. We believe that viewing host
      virus interactions from a transmission perspective helps us understand the
      mechanistic details of antiviral immunity and viral escape. This is particularly
      true for the innate immune system, which typically acts from the very earliest
      stages of the host-virus interaction, and must be bypassed to achieve successful
      infection. With this in mind, here we review the innate sensing of HIV, the
      consequent downstream signaling cascades and the viral restriction that results.
      The centrality of these mechanisms to host defense is illustrated by the array of
      countermeasures that HIV deploys to escape them, despite the coding constraint of
      a 10 kb genome. We consider evasion strategies in detail, in particular the role
      of the HIV capsid and the viral accessory proteins highlighting important
      unanswered questions and discussing future perspectives.

PMID- 29056940
TI  - Complete Chloroplast Genome Sequences and Comparative Analysis of Chenopodium
      quinoa and C. album.
AB  - The Chenopodium genus comprises ~150 species, including Chenopodium quinoa and
      Chenopodium album, two important crops with high nutritional value. To elucidate
      the phylogenetic relationship between the two species, the complete chloroplast
      (cp) genomes of these species were obtained by next generation sequencing. We
      performed comparative analysis of the sequences and, using InDel markers,
      inferred phylogeny and genetic diversity of the Chenopodium genus. The cp genome
      is 152,099 bp (C. quinoa) and 152,167 bp (C. album) long. In total, 119 genes (78
      protein-coding, 37 tRNA, and 4 rRNA) were identified. We found 14 (C. quinoa) and
      15 (C. album) tandem repeats (TRs); 14 TRs were present in both species and C.
      album and C. quinoa each had one species-specific TR. The trnI-GAU intron
      sequences contained one (C. quinoa) or two (C. album) copies of TRs (66 bp); the
      InDel marker was designed based on the copy number variation in TRs. Using the
      InDel markers, we detected this variation in the TR copy number in four species,
      Chenopodium hybridum, Chenopodium pumilio, Chenopodium ficifolium, and
      Chenopodium koraiense, but not in Chenopodium glaucum. A comparison of coding and
      non-coding regions between C. quinoa and C. album revealed divergent sites.
      Nucleotide diversity >0.025 was found in 17 regions-14 were located in the large
      single copy region (LSC), one in the inverted repeats, and two in the small
      single copy region (SSC). A phylogenetic analysis based on 59 protein-coding
      genes from 25 taxa resolved Chenopodioideae monophyletic and sister to Betoideae.
      The complete plastid genome sequences and molecular markers based on divergence
      hotspot regions in the two Chenopodium taxa will help to resolve the phylogenetic
      relationships of Chenopodium.

PMID- 29056941
TI  - Nicotiana benthamiana Elicitor-Inducible Leucine-Rich Repeat Receptor-Like
      Protein Assists Bamboo Mosaic Virus Cell-to-Cell Movement.
AB  - For successful infection, a virus requires various host factors at different
      stages such as translation, targeting, replication, and spreading. One of the
      host genes upregulated after Nicotiana benthamiana infection with Bamboo mosaic
      virus (BaMV), a single-stranded positive-sense RNA potexvirus, assists in viral
      movement. To understand how this host protein is involved in BaMV movement, we
      cloned its full-length cDNA by rapid amplification of cDNA ends. The gene has
      3199 nt and encodes a 969-amino acid polypeptide. The sequence of the encoded
      polypeptide is orthologous to that of N. tabacum elicitor-inducible leucine-rich
      repeat (LRR) receptor-like protein (NtEILP), a plant viral resistance gene, and
      is designated NbEILP. To reveal how NbEILP is involved in BaMV movement, we fused
      green fluorescent protein (GFP) to its C-terminus. Unfortunately, the gene's
      expression in N. benthamiana was beyond our detection limit possibly because of
      its large size (~135 kDa). However, NbEILP at such low expression could still
      enhance BaMV accumulation in inoculated leaves. A short version of NbEILP was
      constructed to remove the LRR domain, NbEILP/DeltaLRR-GFP; the expression of this
      deletion mutant could still enhance BaMV accumulation to 1.7-fold that of the
      control. Hence, the LRR domain in NbEILP is not an essential element in BaMV
      movement. We constructed a few deletion mutants - NbEILP/DeltaLRRDeltaTMD
      (without the transmembrane domain), NbEILP/DeltaLRRDeltaCD (without the
      cytoplasmic domain), and NbEILP/DeltaLRRDeltaSP (without the signal peptide) - to
      examine whether these domains are involved in BaMV movement. For BaMV movement,
      NbEILP requires the signal peptide to target the endoplasmic reticulum and the
      transmembrane domain to retain on the membrane.

PMID- 29056942
TI  - Corrigendum: Different Preclimacteric Events in Apple Cultivars with Modified
      Ripening Physiology.
AB  - [This corrects the article on p. 1502 in vol. 8, PMID: 28928755.].

PMID- 29056943
TI  - Corrigendum: Overexpression of a Grapevine Sucrose Transporter (VvSUC27) in
      Tobacco Improves Plant Growth Rate in the Presence of Sucrose In vitro.
AB  - [This corrects the article on p. 1069 in vol. 8, PMID: 28676814.].

PMID- 29056944
TI  - Importance of frailty and comorbidity in elderly patients with severe aortic
      stenosis.

PMID- 29056945
TI  - Comparison of the low-density lipoprotein cholesterol target value and the
      preventive effect of statins in elderly patients and younger patients.
AB  - OBJECTIVE: To assess whether the low-density lipoprotein cholesterol (LDL-C)
      target value and preventive effect of statins are different between elderly and
      younger patients. METHODS: We investigated 304 patients with previous
      percutaneous coronary intervention who underwent coronary angiography from
      January 2007 to December 2016 for examination of recurrent ischemia beyond the
      early restenosis. Patients were classified into two groups: age >= 75 years
      (elderly group: n = 140) and < 75 years (younger group: n = 164). Relationships
      between the achieved LDL-C level, incidence of late coronary events, and the
      effectiveness of statins were evaluated. RESULTS: During follow-up, 179 patients
      underwent late coronary revascularization. Recurrent ischemia presenting as acute
      coronary syndrome (ACS) occurred in 83 cases. Kaplan-Meier curve analysis
      revealed that in the younger group, recurrent ACS was significantly lower in
      patients with LDL-C < 70 mg/dL than in those with LDL-C ranging from 70 to < 100
      mg/dL (P = 0.035); however, there was no difference between these in the elderly
      group (P = 0.863). Instead, recurrent ACS was less frequent in patients with LDL
      C ranging from 70 mg/dL to < 100 mg/dL than in those with LDL-C >= 100 mg/dL in
      the elderly group (P = 0.033). Statin use was associated with decreased recurrent
      ACS (P = 0.005); moreover, only using statins was an independent predictor in the
      elderly group (HR: 0.375; P = 0.007). CONCLUSIONS: Strict control of LDL-C to <
      70 mg/dL was effective for reducing the incidence of recurrent ACS in younger
      patients. However, LDL-C < 100 mg/dL might be sufficient as the target value of
      LDL-C-lowering therapy for secondary prevention of ischemic events in Japanese
      elderly patients.

PMID- 29056946
TI  - The serum anion gap is associated with disease severity and all-cause mortality
      in coronary artery disease.
AB  - OBJECTIVE: To evaluate the associations between the serum anion gap (AG) with the
      severity and prognosis of coronary artery disease (CAD). METHODS: We measured
      serum electrolytes in 18,115 CAD patients indicated by coronary angiography. The
      serum AG was calculated according to the equation: AG = Na+[(mmol/L) + K+
      (mmol/L)] - [Cl- (mmol/L) + HCO3- (mmol/L)]. RESULTS: A total of 4510 (24.9%)
      participants had their AG levels greater than 16 mmol/L. The serum AG was
      independently associated with measures of CAD severity, including more severe
      clinical types of CAD (P < 0.001) and worse cardiac function (P = 0.004).
      Patients in the 4th quartile of serum AG (>= 15.92 mmol/L) had a 5.171-fold
      increased risk of 30 days all-cause death (P < 0.001). This association was
      robust, even after adjustment for age, sex, evaluated glomerular filtration rate
      [hazard ratio (HR): 4.861, 95% confidence interval (CI): 2.150-10.993, P <
      0.001], clinical diagnosis, severity of coronary artery stenosis, cardiac
      function grades, and other confounders (HR: 3.318, 95% CI: 1.76-2.27, P = 0.009).
      CONCLUSION: In this large population-based study, our findings reveal a high
      percentage of increased serum AG in CAD. Higher AG is associated with more severe
      clinical types of CAD and worse cardiac function. Furthermore, the increased
      serum AG is an independent, significant, and strong predictor of all-cause
      mortality. These findings support a role for the serum AG in the risk
      stratification of CAD.

PMID- 29056947
TI  - Characteristics of elevated cardiac troponin I in patients with acute ischemic
      stroke.
AB  - OBJECTIVE: To study prognostic characteristics of cardiac troponin I (cTnI)
      elevation in acute ischemic stroke. METHODS: We retrospectively studied patients
      (n = 248) with acute ischemic stroke, acute ST-segment elevation myocardial
      infarction, and acute non-ST-elevation myocardial infarction who were treated
      between January 2013 and October 2015. Baseline demographic data and changes in
      cTnI levels among these three groups were compared. Patients with acute ischemic
      stroke were assigned to either the cTnI elevation group (cTnI > 0.034 ng/mL) or
      the no cTnI elevation group (cTnI <= 0.034 ng/mL). Logistic regression analysis
      was used to identify risk factors associated with elevated serum cTnI in patients
      with acute ischemic stroke. Moreover, the duration of hospital stay and incidence
      of major cardiovascular outcomes were compared in patients with acute ischemic
      stroke, with or without elevated cTnI. RESULTS: In this study population of
      patients with acute ischemic stroke (n = 178), acute ST-segment elevation
      myocardial infarction (n = 35), and acute non-ST-elevation myocardial infarction
      (n = 35), patients with acute ischemic stroke with elevated cTnI comprised 18.5%
      of subjects. Patients with elevated cTnI were older and more likely to have a
      history of hypertension. In addition, these patients had higher levels of
      inflammatory markers, reduced renal functions, increased D-dimer levels, higher
      NIH stroke scores, and lower left ventricular ejection fractions. Logistic
      regression analysis showed that both percentage of neutrophil and NIH stroke
      scores were elevated; estimated glomerular filtration rate and left ventricular
      ejection fraction were decreased in patients with acute ischemic stroke who had
      elevated cTnI, and they had more frequent major cardiovascular events during
      hospital stay. CONCLUSION: Elevated cTnI detected in patients with acute ischemic
      stroke, indicated a greater likelihood of poor short-term prognosis during
      hospital stay.

PMID- 29056948
TI  - Association of cardiovascular system medications with cognitive function and
      dementia in older adults living in nursing homes in Australia.
AB  - OBJECTIVE: To examine associations between cardiovascular system medication use
      with cognition function and diagnosis of dementia in older adults living in
      nursing homes in Australia. METHODS: As part of a cross-sectional study of 17
      Australian nursing homes examining quality of life and resource use, we examined
      the association between cognitive impairment and cardiovascular medication use
      (identified using the Anatomical Therapeutic Classification System) using general
      linear regression and logistic regression models. People who were receiving end
      of life care were excluded. RESULTS: Participants included 541 residents with a
      mean age of 85.5 years (+/- 8.5), a mean Psychogeriatric Assessment Scale
      Cognitive Impairment (PAS-Cog) score of 13.3 (+/- 7.7), a prevalence of
      cardiovascular diseases of 44% and of hypertension of 47%. Sixty-four percent of
      participants had been diagnosed with dementia and 72% had received cardiovascular
      system medications within the previous 12 months. Regression models demonstrated
      the use of cardiovascular medications was associated with lower (better) PAS-Cog
      scores [Coefficient (beta) = -3.7; 95% CI: -5.2 to -2.2; P < 0.0001] and a lower
      probability of a dementia diagnosis (OR = 0.44; 95% CI: 0.26 to 0.75, P =
      0.0022). Analysis by subgroups of medications showed cardiac therapy medications
      (C01), beta blocking agents (C07), and renin-angiotensin system agents (C09) were
      associated with lower PAS-Cog scores (better cognition) and lower dementia
      diagnosis probability. CONCLUSIONS: This analysis has demonstrated an association
      between greater cardiovascular system medication use and better cognitive status
      among older adults living in nursing homes. In this population, there may be
      differential access to health care and treatment of cardiovascular risk factors.
      This association warrants further investigation in large cohort studies.

PMID- 29056950
TI  - Delayed asymptomatic progressive aortic dissecting aneurysm in patient with
      STEMI.

PMID- 29056949
TI  - Life-threatening stress-induced cardiomyopathy combined with acute adrenal
      crisis.

PMID- 29056951
TI  - Clopidogrel induced arthritis and fever.

PMID- 29056952
TI  - Acute inferior ST-segment elevation myocardial infarction and previous
      cryptogenic stroke caused by a paradoxical embolism with a concomitant pulmonary
      embolism.

PMID- 29056953
TI  - Percutaneous interventions in elderly patients with atrial fibrillation: left
      atrial ablation and left atrial appendage occlusion.

PMID- 29056954
TI  - Trends in the rates of hospitalizations for acute stroke among patients over 90
      years of age with atrial fibrillation in the United States: from 2005 to 2014.
AB  - BACKGROUND: Acute stroke (AS) rates in patients over 90 years of age (very
      elderly) with atrial fibrillation (AF) in the United States (US) are not known.
      We assessed trends in hospitalizations for AS among very elderly with AF in the
      US from 2005 to 2014. METHODS: We used the nationwide inpatient sample (NIS) from
      the USA; 2005-2014. AF and AS diagnoses were abstracted using international
      classification of diseases, 9th Revision, clinical modification (ICD-9-CM) codes.
      RESULTS: From 2005 to 2014, 3,606,073 hospitalizations of very elderly with AF
      were reported. Of these, 188,948 hospitalizations (141,822 hospitalizations in
      women and 47,126 hospitalizations in men) had AS as the primary diagnosis. Age
      adjusted AS hospitalizations increased in the total cohort (3217/million in 2005
      to 3871/million in 2014), in women (3540/million in 2005 to 4487/million in 2014)
      and in men (2490/million in 2005 to 3173/million in 2014) (P < 0.001).
      Anticoagulation rates increased in women (8% in 2005 to 19.9% in 2014) and in men
      (8.9% in 2005 to 21.6% in 2014). AS rates, though numerically lower than the
      total cohort, showed an increasing trend in anticoagulated patients as well (all
      anticoagulated patients: 212/million in 2005 to 513/million in 2014;
      anticoagulated women: 224/million in 2005 to 529/million in 2014, anticoagulated
      men: 184/million in 2005 to 518/million in 2014). CONCLUSIONS: There is an
      increasing trend in AS hospitalizations among nonagenarians with AF in the US
      despite improving utilization of anticoagulants in this patient population. The
      etiologies driving this alarming trend are unclear and require further study.

PMID- 29056955
TI  - Comparison of long-term outcome between patients aged < 65 years vs. >= 65 years
      after atrial fibrillation ablation.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most frequent arrhythmia, and its
      prevalence is increasing with aging. We aimed to compare the long-term outcome
      data of patients < 65 years vs. >= 65 years who underwent catheter ablation (CA)
      for drug-refractory AF. METHODS: Consecutive patients with primary pulmonary vein
      isolation performed between March 2001 and December 2011, and those who completed
      a five-year of follow-up were divided into two groups: patients aged < 65 years
      into group 1, and patients aged >= 65 into group 2. Long-term outcome data
      concerning mortality, thromboembolic events (TE) and success rates were compared
      between these groups. RESULTS: A total number of 390 patients were included,
      group 1 contained 310 patients, and 80 patients in group 2. In group 2, patients
      had more often impaired renal function (P < 0.001) and thyroid disease (P =
      0.047). A total of fifteen patients died during the 6.63 +/- 2.1 years of follow
      up, with a significantly higher incidence in the older group (8/80 vs. 7/310
      patients, P = 0.004). The majority of fatal outcome was due to cancerous diseases
      in both groups. No difference was observed concerning the long-term TE rate
      (12/310 vs. 4/80 patients, P = 0.75). Rhythm control failed in 25.9% of the
      patients, with no difference between the groups: 26.4% in group 1 vs. 23.7% in
      group 2 (P = 0.67). CONCLUSIONS: Despite growing prevalence of AF in aging
      population, the elderly patients are underrepresented in CA procedures. Similar
      clinical success and TE complication rate are observed between the age-groups.
      Our data suggest more liberal criteria might be applied while selecting patients
      for AF ablation.

PMID- 29056956
TI  - Clinical outcomes of radiofrequency catheter ablation of atrial fibrillation in
      octogenarians-10-year experience of a one high-volume center.
AB  - BACKGROUND: Prevalence of atrial fibrillation (AF) increases with age.
      Radiofrequency catheter ablation (RFCA) is an established treatment option
      superior to antiarrhythmics (AAs). In this study, we investigated safety and
      efficacy of RFCA of AF in octogenarians. METHODS: From our database, we extracted
      procedural and follow-up data for patients >= 80 years with symptomatic AF
      undergoing RFCA and compared this population to RFCA patients <= 50 years. All
      patients underwent pulmonary vein isolation (PVI) supplemented by linear lesions
      in PVI-nonresponders. Arrhythmia-free survival was assessed using seven day
      Holter every three months post procedure. All patients completed their 12 months
      follow-up. RESULTS: Fifty patients aged >= 80 years (80.5 +/- 1.6 years) were
      compared to 259 patients aged <= 50 years (43.5 +/- 5.5 years). The RFCA
      complication rate did not vary between groups. No differences in procedural
      characteristics were seen after being analyzed by type of AF. Among patients with
      paroxysmal AF, 71.4% octogenarian vs. 84.7% young patients was free of any
      arrhythmia, without AAs, after single procedure. For non-paroxysmal AF,
      arrhythmia-free survival without AAs, was considerably lower (58.6% octogenarians
      vs. 81.2% younger patients, P = 0.023). If AAs were used, arrhythmia-free
      survival for paroxysmal AF increased to 90.5% and 92.1% in octogenarians and
      younger patients, respectively; and in non-paroxysmal AF it increased to 79.3%
      vs. 88.4%. CONCLUSIONS: RFCA is a safe and effective strategy to achieve normal
      sinus rhythm in a highly selected group of octogenarians. Paroxysmal AF ablation
      in octogenarians has similar clinical effectiveness as that seen in much younger
      patients. Non-paroxysmal AF ablation has lower, but still reasonable clinical
      effectiveness.

PMID- 29056957
TI  - Atrial fibrillation and CHADS2 score as mortality predictors in young versus
      elderly patients undergoing coronary angiography.

PMID- 29056958
TI  - Renal artery denervation suppresses intractable ventricular arrhythmia in
      patients with left heart thrombosis.

PMID- 29056960
TI  - Complete heart block as presenting symptom of massive pulmonary embolism in an
      elderly patient.

PMID- 29056959
TI  - Left atrial appendage occluder implantation for stroke prevention in elderly
      patients with atrial fibrillation: acute and long-term results.

PMID- 29056961
TI  - Determination of action potential wavelength restitution in Scn5a+/- mouse hearts
      modelling human Brugada syndrome.

PMID- 29056963
TI  - Fusion of Facial Expressions and EEG for Multimodal Emotion Recognition.
AB  - This paper proposes two multimodal fusion methods between brain and peripheral
      signals for emotion recognition. The input signals are electroencephalogram and
      facial expression. The stimuli are based on a subset of movie clips that
      correspond to four specific areas of valance-arousal emotional space (happiness,
      neutral, sadness, and fear). For facial expression detection, four basic emotion
      states (happiness, neutral, sadness, and fear) are detected by a neural network
      classifier. For EEG detection, four basic emotion states and three emotion
      intensity levels (strong, ordinary, and weak) are detected by two support vector
      machines (SVM) classifiers, respectively. Emotion recognition is based on two
      decision-level fusion methods of both EEG and facial expression detections by
      using a sum rule or a production rule. Twenty healthy subjects attended two
      experiments. The results show that the accuracies of two multimodal fusion
      detections are 81.25% and 82.75%, respectively, which are both higher than that
      of facial expression (74.38%) or EEG detection (66.88%). The combination of
      facial expressions and EEG information for emotion recognition compensates for
      their defects as single information sources.

PMID- 29056962
TI  - Chiglitazar Preferentially Regulates Gene Expression via Configuration-Restricted
      Binding and Phosphorylation Inhibition of PPARgamma.
AB  - Type 2 diabetes mellitus is often treated with insulin-sensitizing drugs called
      thiazolidinediones (TZD), which improve insulin resistance and glycemic control.
      Despite their effectiveness in treating diabetes, these drugs provide little
      protection from eminent cardiovascular disease associated with diabetes. Here we
      demonstrate how chiglitazar, a configuration-restricted non-TZD peroxisome
      proliferator-activated receptor (PPAR) pan agonist with moderate transcription
      activity, preferentially regulates ANGPTL4 and PDK4, which are involved in
      glucose and lipid metabolism. CDK5-mediated phosphorylation at serine 273 (S273)
      is a unique regulatory mechanism reserved for PPARgamma, and this event is linked
      to insulin resistance in type 2 diabetes mellitus. Our data demonstrates that
      chiglitazar modulates gene expression differently from two TZDs, rosiglitazone
      and pioglitazone, via its configuration-restricted binding and phosphorylation
      inhibition of PPARgamma. Chiglitazar induced significantly greater expression of
      ANGPTL4 and PDK4 than rosiglitazone and pioglitazone in different cell models.
      These increased expressions were dependent on the phosphorylation status of
      PPARgamma at S273. Furthermore, ChIP and AlphaScreen assays showed that
      phosphorylation at S273 inhibited promoter binding and cofactor recruitment by
      PPARgamma. Based on these results, activities from pan agonist chiglitazar can be
      an effective part of a long-term therapeutic strategy for treating type 2
      diabetes in a more balanced action among its targeted organs.

PMID- 29056964
TI  - Hyperbolic Modeling of Subthalamic Nucleus Cells to Investigate the Effect of
      Dopamine Depletion.
AB  - To investigate how different types of neurons can produce well-known spiking
      patterns, a new computationally efficient model is proposed in this paper. This
      model can help realize the neuronal interconnection issues. The model can
      demonstrate various neuronal behaviors observed in vivo through simple parameter
      modification. The behaviors include tonic and phasic spiking, tonic and phasic
      bursting, class 1 and class 2 excitability, rebound spike, rebound burst,
      subthreshold oscillation, and accommodated spiking along with inhibition neuron
      responses. Here, we investigate the neuronal spiking patterns in Parkinson's
      disease through our proposed model. Abnormal pattern of subthalamic nucleus in
      Parkinson's disease can be studied through variations in the shape and frequency
      of firing patterns. Our proposed model introduces mathematical equations, where
      these patterns can be derived and clearly differentiated from one another. The
      irregular and arrhythmic behaviors of subthalamic nucleus firing pattern under
      normal conditions can easily be transformed to those caused by Parkinson's
      disease through simple parameter modifications in the proposed model. This model
      can explicitly show the change of neuronal activity patterns in Parkinson's
      disease, which may eventually lead to effective treatment with deep brain
      stimulation devices.

PMID- 29056965
TI  - Salt, Aldosterone, and Parathyroid Hormone: What Is the Relevance for Organ
      Damage?
AB  - Structured interventions on lifestyle have been suggested as a cost-effective
      strategy for prevention of cardiovascular disease. Epidemiologic studies
      demonstrate that dietary salt restriction effectively decreases blood pressure,
      but its influence on cardiovascular morbidity and mortality is still under
      debate. Evidence gathered from studies conducted in patients with primary
      aldosteronism, essential hypertension, or heart failure demonstrates that long
      term exposure to elevated aldosterone results in cardiac structural and
      functional changes that are independent of blood pressure. Animal experiments and
      initial clinical studies indicate that aldosterone damages the heart only in the
      context of an inappropriately elevated salt status. Recent evidence suggests that
      aldosterone might functionally interact with the parathyroid hormone and thereby
      affect calcium homeostasis with important sequelae for bone mineral density and
      strength. The interaction between aldosterone and parathyroid hormone might have
      implications also for the heart. Elevated dietary salt is associated on the one
      hand with increased urinary calcium excretion and, on the other hand, could
      facilitate the interaction between aldosterone and parathyroid hormone at the
      cellular level. This review summarizes the evidence supporting the contribution
      of salt and aldosterone to cardiovascular disease and the possible cardiac and
      skeletal consequences of the mutual interplay between aldosterone, parathyroid
      hormone, and salt.

PMID- 29056966
TI  - Endocrine Therapy Initiation among Older Women with Ductal Carcinoma In Situ.
AB  - BACKGROUND: Although treatment of ductal carcinoma in situ (DCIS) is
      controversial, national guidelines recommend considering endocrine therapy for
      women with estrogen receptor- (ER-) positive DCIS or those undergoing breast
      conserving surgery (BCS) without radiation. We evaluated uptake and predictors of
      endocrine therapy use among older women with DCIS. METHODS: In the SEER-Medicare
      database, we identified women aged 65+ years diagnosed with DCIS during 2007
      2011. We evaluated demographic, tumor, and treatment characteristics associated
      with endocrine therapy initiation. RESULTS: Among 2,945 women with DCIS, 41%
      initiated endocrine therapy (66% tamoxifen, 34% aromatase inhibitors). Initiation
      was more common among women with ER-positive than ER-negative DCIS (48% versus
      16%; HR = 3.75, 95% CI: 2.91-4.83); 28% of women with unknown ER status initiated
      endocrine therapy. Initiation was less common after BCS alone compared to BCS
      with radiation (32% versus 50%; HR = 0.69, 95% CI: 0.59-0.80). CONCLUSIONS: Less
      than half of older women with DCIS initiate endocrine therapy to prevent second
      breast cancers. Our findings suggest use was more common, but not exclusive,
      among women with ER-positive DCIS, but not among women who underwent BCS alone.
      Endocrine therapy should be targeted toward patients most likely to benefit from
      its use.

PMID- 29056967
TI  - Analysis of Three Compounds in Flos Farfarae by Capillary Electrophoresis with
      Large-Volume Sample Stacking.
AB  - The aim of this study was to develop a method combining an online concentration
      and high-efficiency capillary electrophoresis separation to analyze and detect
      three compounds (rutin, hyperoside, and chlorogenic acid) in Flos Farfarae. In
      order to get good resolution and enrichment, several parameters such as the
      choice of running buffer, pH and concentration of the running buffer, organic
      modifier, temperature, and separation voltage were all investigated. The
      optimized conditions were obtained as follows: the buffer of 40 mM NaH2P04-40 mM
      Borax-30% v/v methanol (pH 9.0); the sample hydrodynamic injection of up to 4 s
      at 0.5 psi; 20 kV applied voltage. The diode-array detector was used, and the
      detection wavelength was 364 nm. Based on peak area, higher levels of selective
      and sensitive improvements in analysis were observed and about 14-, 26-, and 5
      fold enrichment of rutin, hyperoside, and chlorogenic acid were achieved,
      respectively. This method was successfully applied to determine the three
      compounds in Flos Farfarae. The linear curve of peak response versus
      concentration was from 20 to 400 ug/ml, 16.5 to 330 ug/mL, and 25 to 500 ug/mL,
      respectively. The regression coefficients were 0.9998, 0.9999, and 0.9991,
      respectively.

PMID- 29056968
TI  - Effect of Injection Molding Melt Temperatures on PLGA Craniofacial Plate
      Properties during In Vitro Degradation.
AB  - The purpose of this article is to present mechanical and physicochemical
      properties during in vitro degradation of PLGA material as craniofacial plates
      based on different values of injection molded temperatures. Injection molded
      plates were submitted to in vitro degradation in a thermostat bath at 37 +/- 1
      degrees C by 16 weeks. The material was removed after 15, 30, 60, and 120 days;
      then bending stiffness, crystallinity, molecular weights, and viscoelasticity
      were studied. A significant decrease of molecular weight and mechanical
      properties over time and a difference in FT-IR after 60 days showed faster
      degradation of the material in the geometry studied. DSC analysis confirmed that
      the crystallization occurred, especially in higher melt temperature condition.
      DMA analysis suggests a greater contribution of the viscous component of higher
      temperature than lower temperature in thermomechanical behavior. The results
      suggest that physical-mechanical properties of PLGA plates among degradation
      differ per injection molding temperatures.

PMID- 29056969
TI  - Clinical Characteristics and Laboratory Identification of Aerococcus Infections:
      An Australian Tertiary Centre Perspective.
AB  - Aerococci uncommonly cause urinary tract (UTI) and bloodstream infections (BSI).
      The clinical characteristics and laboratory identification rates of Aerococcus in
      the Australian context are unknown. A retrospective observational cohort study of
      patients with positive Aerococcus cultures between 2010 and 2015 was performed.
      Patients were analysed according to predefined "asymptomatic bacteriuria," "UTI,"
      and "BSI" groups. Forty-seven [40 (85%) for urine and 7 (15%) for blood] isolates
      were identified [38% male, median age of 79 (IQR 62-85) years], with
      corresponding identification rates of 24.2/100,000/year for urine (0.02%) and
      7.3/100,000/year for blood cultures (0.007%). Since the use of matrix-assisted
      laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS)
      identification rate in urine has increased from 14.7/100,000/year to
      32/100,000/year (p = 0.02). For urine isolates, 14 (35%) met the definition for
      UTI whilst 26 (65%) were "asymptomatic bacteriuria." Underlying urological
      abnormalities, catheterisation, and polymicrobial growth were common. Seventy
      percent of bacteriuria was treated regardless of colonisation or active infection
      status. Symptomatic patients were more likely to receive treatment (OR 7.2, 95%
      CI 1.4-35.3). In patients with BSI, 1 (14.2%) had endocarditis and 1 (14.2%)
      died. The majority of isolates were susceptible to penicillin (11/12 tested,
      92%).

PMID- 29056971
TI  - Delayed Presentation of Posttraumatic Diaphragmatic Hernia Masquerading as
      Recurrent Acute Asthmatic Attack.
AB  - Diaphragmatic hernia following blunt abdominal injury is extremely rare and often
      diagnosed late. Missed diagnosis is also common with this condition. We herein
      present a delayed presentation of diaphragmatic hernia following blunt abdominal
      injury that was initially misdiagnosed as recurrent acute asthmatic attack due to
      repeated presentation with episodic difficulty in breathing.

PMID- 29056970
TI  - Factors for a Successful Laparoscopic Hysterectomy in Very Large Uteri.
AB  - Minimally invasive hysterectomy is a standard procedure. Different approaches, as
      laparoscopically assisted vaginal hysterectomy, vaginal hysterectomy, and
      subtotal and total laparoscopic hysterectomy, have been described and evaluated
      by various investigations as safe and cost-effective methods. In particular, in
      comparison to abdominal hysterectomy, the minimally invasive methods have
      undoubted advantages for the patients. The main reason for a primary abdominal
      hysterectomy or conversion to abdominal hysterectomy during a minimal invasive
      approach is the uterine size. We describe our course of action in the
      retrospective analysis of five cases of total minimal-access hysterectomy,
      combining the laparoscopic subtotal hysterectomy and the vaginal extirpation of
      the cervix in uterine myomatosis with a uterine weight of more than 1000 grams,
      and discuss the factors that limit the use of laparoscopy in the treatment of big
      uteri. Trail Registration. The case report is registered in Research Registry
      under the UIN researchregistry743.

PMID- 29056972
TI  - Methotrexate and Valproic Acid Affect Early Neurogenesis of Human Amniotic Fluid
      Stem Cells from Myelomeningocele.
AB  - Myelomeningocele (MMC) is a severe type of neural tube defect (NTD), in which the
      backbone and spinal canal do not close completely during early embryonic
      development. This condition results in serious morbidity and increased mortality
      after birth. Folic acid significantly reduces, and conversely, folate antagonist
      methotrexate (MTX) and valproic acid (VPA) increase the occurrence of NTDs,
      including MMC. How these pharmacological agents exactly influence the early
      neurulation process is still largely unclear. Here, we characterized human
      amniotic fluid-derived stem cells (AFSCs) from prenatally diagnosed MMC and
      observed an effect of MTX and VPA administration on the early neural
      differentiation process. We found that MMC-derived AFSCs highly expressed early
      neural and radial glial genes that were negatively affected by MTX and VPA
      exposure. In conclusion, we setup a human cell model of MMC to study early
      neurogenesis and for drug screening purposes. We also proposed the detection of
      early neural gene expression in AFSCs as an additional MMC diagnostic tool.

PMID- 29056973
TI  - Rationale and Design of the First Double-Blind, Placebo-Controlled Trial with
      Allogeneic Adipose Tissue-Derived Stromal Cell Therapy in Patients with Ischemic
      Heart Failure: A Phase II Danish Multicentre Study.
AB  - BACKGROUND: Ischemic heart failure (IHF) has a poor prognosis in spite of optimal
      therapy. We have established a new allogeneic Cardiology Stem Cell Centre adipose
      derived stromal cell (CSCC_ASC) product from healthy donors. It is produced
      without animal products, in closed bioreactor systems and cryopreserved as an off
      the-shelf product ready to use. STUDY DESIGN: A multicentre, double-blind,
      placebo-controlled phase II study with direct intramyocardial injections of
      allogeneic CSCC_ASC in patients with chronic IHF. A total of 81 patients will be
      randomised at 2 : 1 to CSCC_ASC or placebo. There is no HLA tissue type matching
      needed between the patients and the donors. METHODS: The treatment will be
      delivered by direct injections into the myocardium. The primary endpoint is
      change in the left ventricle endsystolic volume at 6-month follow-up. Secondary
      endpoints are safety and changes in left ventricle ejection fraction, myocardial
      mass, stroke volume, and cardiac output. Other secondary endpoints are change in
      clinical symptoms, 6-minute walking test, and the quality of life after 6 and 12
      months. CONCLUSION: The aim of the present study is to demonstrate safety and the
      regenerative efficacy of the allogeneic CSCC_ASC product from healthy donors in a
      double-blind, placebo-controlled, multicentre study in patients with IHF.

PMID- 29056974
TI  - Avoidance of Total Knee Arthroplasty in Early Osteoarthritis of the Knee with
      Intra-Articular Implantation of Autologous Activated Peripheral Blood Stem Cells
      versus Hyaluronic Acid: A Randomized Controlled Trial with Differential Effects
      of Growth Factor Addition.
AB  - In this randomized controlled trial, in early osteoarthritis (OA) that failed
      conservative intervention, the need for total knee arthroplasty (TKA) and WOMAC
      scores were evaluated, following a combination of arthroscopic microdrilling
      mesenchymal cell stimulation (MCS) and repeated intra-articular (IA) autologous
      activated peripheral blood stem cells (AAPBSCs) with growth factor addition (GFA)
      and hyaluronic acid (HA) versus IA-HA alone. Leukapheresis-harvested AAPBSCs were
      administered as three weekly IA injections combined with HA and GFA (platelet
      rich plasma [PRP] and granulocyte colony-stimulating factor [hG-CSF]) and MCS in
      group 1 and in group 2 but without hG-CSF while group 3 received IA-HA alone.
      Each group of 20 patients was evaluated at baseline and at 1, 6, and, 12 months.
      At 12 months, all patients in the AAPBSC groups were surgical intervention free
      compared to three patients needing TKA in group 3 (p < 0.033). Total WOMAC scores
      showed statistically significant improvements at 6 and 12 months for the AAPBSC
      groups versus controls. There were no notable adverse events. We have shown
      avoidance of TKA in the AAPBSC groups at 12 months and potent, early, and
      sustained symptom alleviation through GFA versus HA alone. Differential effects
      of hG-CSF were noted with an earlier onset of symptom alleviation throughout.

PMID- 29056977
TI  - Caring for our most vulnerable patients.

PMID- 29056975
TI  - Exploration of the Risk Factors of Generalized and Central Obesity among
      Adolescents in North Lebanon.
AB  - Adolescents' obesity is an emerging public health problem globally and in the
      Arab countries. Alarming rates of overweight/obesity have been rising
      progressively in Lebanon. However, the risk factors for the development of
      adolescents' obesity have not yet been thoroughly explored in North Lebanon. To
      determine the dietary and lifestyle risk factors associated with generalized and
      central obesity among adolescents living in Tripoli, a cross-sectional survey was
      conducted including a representative sample of 311 students aged 11-16 years from
      both sexes chosen from public and private schools in Tripoli. Data were collected
      using a standardized questionnaire to determine sociodemographic characteristics,
      dietary patterns, and physical activity and sedentary behaviors. Body mass index
      (BMI) was evaluated using the Center for Disease Control BMI for age percentiles.
      Central obesity was assessed using both waist-to-height ratio and gender-specific
      waist circumference for age indices. Multiple logistic regression analysis
      revealed that skipping breakfast and physical inactivity were the most
      significant independent risk factors associated with both generalized and central
      obesity. In addition, higher screen time and male gender were associated with
      increased risk for generalized and central obesity, respectively. Intervention
      strategies to prevent the development of obesity should be implemented among
      adolescent students to encourage regular breakfast intake and adopting healthy
      dietary and lifestyle behaviors.

PMID- 29056978
TI  - Screening for Disruptive Behaviour Problems in Preschool Children in Primary
      Health Care Settings.
AB  - Disruptive behaviour problems in preschool children are significant risk factors
      for, and potential components of, neurodevelopmental and mental health disorders.
      Some non-compliance, temper tantrums and aggression between two and five years of
      age are normal and transient. However, problematic levels of disruptive
      behaviour, specifically when accompanied by functional impairment and/or
      significant distress, should be identified because early intervention can improve
      outcome trajectories. This position statement provides an approach to early
      identification using clinical screening at periodic health examinations, followed
      by a systematic mental health examination that includes standardized measures.
      The practitioner should consider a range of environmental, developmental, family
      and parent-child relationship factors to evaluate the clinical significance of
      disruptive behaviours. Options within a management plan include regular
      monitoring accompanied by health guidance and parenting advice, referral to
      parent behaviour training as a core evidence-based intervention, and referral to
      specialty care for preschool children with significant disruptive behaviours,
      developmental or mental health comorbidities, or who are not responding to first
      line interventions.

PMID- 29056976
TI  - Interactions between Neighbourhood Urban Form and Socioeconomic Status and Their
      Associations with Anthropometric Measurements in Canadian Adults.
AB  - Neighbourhood-level socioeconomic composition and built context are correlates of
      weight-related behaviours. We investigated the relations between objective
      measures of neighbourhood design and socioeconomic status (SES) and their
      interaction, in relation to self-reported waist circumference (WC), waist-to-hip
      ratio, and body mass index (BMI) in a sample of Canadian adults (n = 851 from 12
      Calgary neighbourhoods). WC and BMI were higher among residents of disadvantaged
      neighbourhoods, independent of neighbourhood design (grid, warped grid, and
      curvilinear street patterns) and individual-level characteristics (sex, age,
      education, income, dog ownership, marital status, number of dependents, motor
      vehicle access, smoking, sleep, mental health, physical health, and past attempts
      to modify bodyweight). The association between neighbourhood-level SES and WC was
      modified by neighbourhood design; WC was higher in disadvantaged-curvilinear
      neighbourhoods and lower in advantaged-grid neighbourhoods. Policies making less
      obesogenic neighbourhoods affordable to low socioeconomic households and that
      improve the supportiveness for behaviours leading to healthy weight in low
      socioeconomic neighbourhoods are necessary.

PMID- 29056979
TI  - A Critique of the New Canadian Fetal Alcohol Spectrum Disorder Guideline.
AB  - A new Fetal Alcohol Spectrum Disorder (FASD) guideline was published in the
      Canadian Medical Association Journal in 2016. This is relevant to the mental
      health field as mental health symptoms and psychiatric disorders are often
      identified as associated with and/or part of FASD presentations. Unfortunately,
      the new guideline has not advanced understanding of the interface between FASD
      and mental health problems; rather it may contribute to additional confusion. For
      example, a new recommendation to include additional mental health symptoms, such
      as anxiety and affect dysregulation, as manifestations contributing to a
      diagnosis of FASD is particularly concerning given the paucity of evidence
      supporting this assertion and the potential to distort delivery of mental health
      interventions for mental health problems. In addition, the guideline
      recommendation for introducing an "at risk for FASD" designation is not without
      risk. An appeal is made for greater scrutiny in the construction of diagnostic
      criteria and guidelines and for a more careful delineation of causal
      relationships and comorbidities to better inform the delivery of evidence-based
      mental health care.

PMID- 29056980
TI  - Youth Mental Health, Family Practice, and Knowledge Translation Video Games about
      Psychosis: Family Physicians' Perspectives.
AB  - OBJECTIVE: Family practitioners face many challenges providing mental healthcare
      to youth. Digital technology may offer solutions, but the products often need to
      be adapted for primary care. This study reports on family physicians'
      perspectives on the relevance and feasibility of a digital knowledge translation
      (KT) tool, a set of video games, designed to raise awareness about psychosis,
      marijuana use, and facilitate access to mental health services among youth.
      METHOD: As part of an integrated knowledge translation project, five family
      physicians from a family health team participated in a focus group. The focus
      group delved into their perspectives on treating youth with mental health
      concerns while exploring their views on implementing the digital KT tool in their
      practice. Qualitative data was analyzed using thematic analysis to identify
      patterns, concepts, and themes in the transcripts. RESULTS: Three themes were
      identified: (a) challenges in assessing youth with mental health concerns related
      to training, time constraints, and navigating the system; (b) feedback on the KT
      tool; and, (c) ideas on how to integrate it into a primary care practice.
      CONCLUSIONS: Family practitioners felt that the proposed video game KT tool could
      be used to address youth's mental health and addictions issues in primary care
      settings.

PMID- 29056981
TI  - Children's Shyness in a Surgical Setting.
AB  - OBJECTIVE: We examined the relation between temperament and preoperative anxiety
      in 40 children (aged 8-13) who were undergoing elective surgery one week prior to
      surgery Time 1 (T1) and on the day of surgery Time 2 (T2). METHOD: Children's
      temperamental shyness was examined using the Colorado Childhood Temperament
      Inventory at T1, and preoperative anxiety was assessed using the Children's
      Perioperative Multidimensional Anxiety Scale at T1 and T2. RESULTS: We found that
      temperamental shyness predicted lower preoperative anxiety at T1 (beta = -10.78;
      p = .03) and at T2 (beta = -12.31; p = .03). CONCLUSION: We speculate that
      temperamentally shy children although seemingly paradoxical, our findings suggest
      that temperamentally shy children may have developed coping strategies from
      dealing with persistent anxiety in their everyday environments, and they may use
      these coping skills in the surgical context. These findings are discussed in
      terms of their theoretical and practical implications for understanding person by
      context interactions and managing children's preoperative anxiety.

PMID- 29056982
TI  - Perception of Interprofessional Collaboration and Co-Location of Specialists and
      Primary Care Teams in Youth Mental Health.
AB  - OBJECTIVES: Interprofessional collaboration is a cornerstone of youth mental
      health collaborative care models. This article presents quantitative results from
      a mixed-methods study. It analyses the organizational predictors of the
      perception of interprofessional collaboration of professionals comparing two
      models of services within recently constituted youth mental health collaborative
      care teams. METHODS: Professionals (n=104) belonging to six health and social
      services institutions completed an online survey measuring their perceptions of
      interprofessional collaboration through a validated questionnaire, the PINCOM-Q.
      RESULTS: Results suggest that the integrated model of collaborative care in which
      specialized resources are co-located with the primary care teams is the main
      significant predictor of positive perception of interprofessional collaborations
      in the youth mental health team. CONCLUSION: More research on the relation
      between service delivery models and interprofessional relations could help
      support the successful implementation of collaborative care in youth mental
      health.

PMID- 29056983
TI  - Glutamate Genetics in Obsessive-Compulsive Disorder: A Review.
AB  - OBJECTIVE: Obsessive-compulsive disorder (OCD) is common and debilitating with
      patients exhibiting persistent intrusive thoughts (obsessions), repetitive
      ritualistic behaviours (compulsions) and anxiety. While it is known that OCD is
      highly heritable, the specific genetic risk factors for OCD are still largely
      unknown. The etiology of OCD has also not been fully elucidated but there is
      growing evidence that glutamate signaling dysfunction in the cortico-striatal
      thalamo-cortical (CSTC) circuitry plays a role in its pathogenesis. METHODS: We
      conducted a focused review of recent literature on the role of glutamate genes in
      OCD. RESULTS: There have been several recent discoveries in the SAPAP (DLGAP)
      family, SLC1A1, and GRIN/GRIK families of proteins related to OCD. CONCLUSION:
      There is growing evidence supporting a role for genetic variation leading to
      dysfunctional glutamate signaling in OCD. Based on this new evidence we
      hypothesize that sustained glutamatergic neurotransmission in key areas of the
      brain may be contributing to the etiology of OCD.

PMID- 29056984
TI  - Housing Instability and Concurrent Substance use and Mental Health Concerns: An
      Examination of Canadian Youth.
AB  - OBJECTIVE: Though previous research has identified the high burden of mental
      health and addiction (MHA) concerns among precariously housed youth, earlier
      studies have not examined differences in MHA concerns among housing insecure
      Canadian youth across sectors. This study examines this issue using the Global
      Appraisal of Individual Needs Short Screener (GAIN-SS) in a cross-sectoral sample
      of Canadian youth. METHOD: A total of 2605 youth ages 12 to 24 seeking services
      across sectors completed the GAIN-SS and a sociodemographic form. The analyses
      described demographic variables and sector of presentation, then evaluated
      internalizing, externalizing, substance use, and crime/violence concerns based on
      housing status. RESULTS: While many precariously housed youth presented through
      the housing/outreach/support sector, 33.6% presented to other sectors. Housing
      groups endorsed comparably high levels of internalizing and externalizing
      problems. However, precariously housed youth reported higher rates of problematic
      substance use (OR = 1.54; 95% CI 1.25, 1.88; p < 0.01) and crime/violence issues
      (OR = 1.95; 95% CI 1.54, 2.46; p < 0.01). Precariously housed youth were 48% more
      likely to endorse concurrent disorders (OR = 1.48; 95% CI 1.21, 1.82; p < 0.01),
      which was largely driven by the high rate of concurrent disorders among
      precariously housed females. CONCLUSIONS: Since precariously housed youth with
      multiple clinical needs presented across sectors, attention must be given to
      screening for both housing stability and MHA and building stronger cross-sectoral
      partnerships. The findings should encourage systematic screening, MHA training
      and capacity building within housing sectors as well as integrated services
      across all youth-serving organizations.

PMID- 29056985
TI  - An Exploration of Positive Parenting in Relation to Psychopathology for Youth
      with a Diagnosis of Bipolar Spectrum Disorder.
AB  - OBJECTIVE: Bipolar Spectrum Disorder (BSD) is a severe psychiatric disorder
      associated with a host of deleterious sequelae. While researchers have found a
      robust link between parenting variables and psychopathology for youth with BSD,
      few have examined positive parenting factors and associated psychopathology for
      these youth. Furthermore, conclusions from extant literature are hindered by a)
      exploring a limited range of parenting variables and b) employing retrospective
      reports of parenting with adult populations. This study addressed these gaps by
      examining how a range of contemporaneously-measured positive parenting variables
      were related to psychopathology among youth with a BSD diagnosis. METHODS: One
      hundred fifty families with a youth aged 5-16 years participated in this study
      and completed screening for a mood disorder through a tertiary care facility.
      Participants completed measures of depression, mania, behavioural difficulties,
      and the parent-child relationship. RESULTS: Parental characteristics (limit
      setting, autonomy granting, egalitarian views) were related to lower levels of
      psychopathology for youth screened for BSD. CONCLUSIONS: Taken together, the
      results from this study contribute to our understanding of the relation between
      positive parenting characteristics and psychopathology for youth with a diagnosis
      of BSD.

PMID- 29056986
TI  - Adjunctive Trazodone and Depression Outcome in Adolescents Treated with Serotonin
      Re-uptake Inhibitors.
AB  - OBJECTIVES: Recent published evidence suggests that adjunctive trazodone
      treatment may limit serotonin reuptake inhibitor (SRI) response in depressed
      adolescents in the context of a controlled trial. This study examined the effects
      of adjunctive trazodone on depression outcome in adolescents in a naturalistic
      treatment environment. METHODS: We conducted a cohort study through chart review
      of a clinical sample. Patients in our sample were 15 to 18 years of age treated
      with either a selective serotonin reuptake inhibitor or serotonin and
      norepinephrine reuptake inhibitor. The treatment took place in the setting of a
      partial hospitalization program at a tertiary care centre from 2009-2014. The
      main outcome measure was the change in Beck Depression Inventory II (BDI-II)
      score from admission to discharge. We compared this outcome in patients who were
      exposed to adjunctive trazodone treatment compared to adolescents who did not
      receive trazodone in the final four weeks of the program. RESULTS: Exposure to
      trazodone was significantly associated with non-response to treatment in our
      sample (n= 35; beta1= -7.76; 95% CI -0.52 to - 15.0; p<0.05; R2 = 0.13). In
      exploring potential confounders, higher baseline BDI-II scores appeared to
      predict greater change in BDI-II scores from pre- to post-treatment. CONCLUSION:
      In keeping with previous research, we found that trazodone exposure was
      associated with treatment non-response in adolescents taking SRIs. The findings
      should be interpreted cautiously since they are limited by small sample size.
      Future randomized controlled trials of trazodone in samples of adolescents taking
      SRIs for depression are warranted.

PMID- 29056988
TI  - ?

PMID- 29056989
TI  - Genetic testing in antiplatelet therapy - not effective for perioperative
      bleeding.

PMID- 29056990
TI  - Polish trials influencing 2017 European Society of Cardiology guidelines on acute
      myocardial infarction in patients presenting with ST-segment elevation.

PMID- 29056991
TI  - Atherosclerotic renovascular disease - epidemiology, treatment and current
      challenges.
AB  - The neutral results of recent large randomized controlled trials comparing renal
      revascularization with optimal medical therapy in patients with atherosclerotic
      renovascular disease (ARVD) have cast doubt on the role of revascularization in
      the management of unselected patients with this condition. However, these studies
      have strengthened the evidence base for the role of contemporary intensive
      medical vascular protection therapy and aggressive risk factor control in
      improving clinical outcomes in ARVD. Patients presenting with 'high-risk'
      clinical features such as uncontrolled hypertension, rapidly declining renal
      function or flash pulmonary oedema are underrepresented in these studies; hence
      these results may not be applicable to all patients with ARVD. In this 'high
      risk' subgroup, conservative management may not be sufficient in preventing
      adverse events, and indeed, observational evidence suggests that this specific
      patient subgroup may gain benefit from timely renal revascularization. Current
      challenges include the development of novel diagnostic techniques to establish
      haemodynamic significance of a stenosis, patient risk stratification and
      prediction of post-revascularization outcomes to ultimately facilitate patient
      selection for revascularization. In this paper we describe the epidemiology of
      this condition and discuss treatment recommendations for this condition in light
      of the results of recent randomized controlled trials while highlighting
      important clinical unmet needs and challenges faced by clinicians managing this
      condition.

PMID- 29056992
TI  - Association of polymorphisms of platelet receptors GPIa (807C>T), GPVI
      (13254T>C), and P2Y12 (34C>T and H1/H2 haplotype) with increased risk of
      periprocedural bleeding in patients undergoing coronary angiography/percutaneous
      coronary intervention.
AB  - INTRODUCTION: Periprocedural bleeding related to coronary angiography (CAG) or
      percutaneous coronary intervention (PCI) is associated with worse prognosis.
      Determining genetic variations associated with increased bleeding risk may help
      to identify high-risk patients. AIM: To analyse the association between single
      nucleotide polymorphisms (SNPs) of crucial haemostatic platelet receptors (GPIa,
      GPVI, P2Y12) and the risk of periprocedural bleeding complications related to
      CAG/PCI. MATERIAL AND METHODS: The population consisted of 73 patients with
      ischaemic heart disease who developed bleeding complications within 30 days after
      CAG/PCI and 331 patients without bleeding. The frequency of SNPs of GPIa 807C/T,
      GPVI 13254T/C, P2Y12 32C/T, and P2Y12 H1/H2 haplotype was analysed using
      polymerase chain reaction (PCR) hybridization methods. RESULTS: The prevalence of
      variant alleles GPIa 807T, GPVI 13254C, P2Y12 34T, and P2Y12 H2 haplotype in the
      total study population was 56.7%, 20.3%, 56.2%, and 24.3%, respectively. The
      presence of variant alleles was not related to increased risk of periprocedural
      bleeding: GPIa 807C/T (OR = 1.29, 95% CI: 0.75-2.24, p = 0.334), GPVI 12354T/C
      (OR = 0.82, 95% CI: 0.40-1.64, p = 0.551), P2Y12 34C/T (OR = 0.71, 95% CI: 0.42
      1.22, p = 0.189), P2Y12 H1/H2 haplotype (OR = 0.69, 95% CI: 0.35-1.36, p =
      0.258). The frequency of the homozygous form of P2Y12 H2 haplotype was higher in
      the group of patients who developed bleeding (OR = 2.79, 95% CI: 0.51-13.77, p =
      0.161). CONCLUSIONS: No significant association of the SNPs of GPIa 807C/T, GPVI
      13254T/C, P2Y12 32C/T, and P2Y12 H1/H2 haplotype with increased risk of
      periprocedural bleeding was found in patients with ischaemic heart disease
      undergoing CAG/PCI.

PMID- 29056993
TI  - Factors related to on-treatment platelet aggregation assessed by multiple
      electrode aggregometry in percutaneous coronary intervention patients on
      clopidogrel and aspirin.
AB  - INTRODUCTION: There is ongoing controversy concerning the clinical value of
      platelet function monitoring in patients undergoing percutaneous coronary
      interventions (PCI). Patients at risk of high on-treatment platelet aggregation
      (HPR) may benefit most from such monitoring. AIM: To define the factors related
      to HPR on aspirin and clopidogrel, looking at a wider spectrum of variables than
      those assessed in some previous studies. MATERIAL AND METHODS: We assessed
      platelet function in 908 patients on clopidogrel and aspirin after PCI using the
      multielectrode aggregometry system Multiplate to define which clinical,
      procedural and laboratory factors are related to on-treatment platelet
      aggregation in response to aspirin and clopidogrel either as linear values or
      using established cutoff values for HPR. RESULTS: We found that in PCI patients
      on clopidogrel and aspirin, age (OR per year 1.06; 95% CI: 1.024-1.097; p =
      0.001), gender (OR = 0.319; 95% CI: 0.139-0.731; p = 0.007), active smoking (OR =
      2.57; 95% CI: 1.29-5.15; p = 0.008), diabetes (beta = 37.6; 95% CI: 16.5-58.8; p
      = 0.001) and hypertension (beta = 26.9; 95% CI: 6.73-47.1; p = 0.009) are
      independently linked to platelet aggregation values treated as linear values and
      as dichotomous variables at the accepted cutoffs. The same is true for stented
      segment length (OR per mm 1.033; 95% CI: 1.010-1.057; p = 0.009) and stent
      inflation pressure (OR per atmosphere 0.862; 95% CI: 0.772-0.963; p = 0.002).
      CONCLUSIONS: The study shows that, contrary to some earlier data, in the tested
      cohort women are better clopidogrel responders, but more often aspirin low
      responders. Older age, active smoking, diabetes and hypertension all predispose
      to HPR. A novel finding is that stented segment length is an independent
      predictor of lower response both to aspirin and clopidogrel, possibly as a marker
      of more diffuse atherosclerosis.

PMID- 29056994
TI  - Factors affecting treatment, management and mortality in cases of retroperitoneal
      hematoma after cardiac catheterization: a single-center experience.
AB  - INTRODUCTION: There is little information available on the clinical aspects,
      results, treatment and management of cardiac catheterization-related
      retroperitoneal hematoma. Data on the subject are rather limited, and current
      publications are based on a limited number of retrospective cohort studies and
      case reports. AIM: To perform a retrospective analysis of the demographic,
      clinical, and in-hospital results of patients who developed retroperitoneal
      hematoma (RPH) after cardiac catheterization (CC). MATERIAL AND METHODS: The
      cases of 124,064 patients who had CCs between January 2010 and October 2016 were
      retrospectively analyzed. Patients diagnosed with RPH were classified into three
      groups depending on the method of treatment: conservative (group 1), endovascular
      stenting (group 2), and surgery (group 3). The independent risk factors, based on
      RPH-related mortality, were determined by logistic regression analysis. RESULTS:
      Of the 68 (0.054%) patients with RPH, 75% received conservative treatment, 13.2%
      underwent angiographic stent placement, and 11.7% had surgical treatment. Red
      blood cell packets (RBCPs) (p = 0.043), duration of hospitalization (p = 0.007),
      and mortality rates (p = 0.006) were statistically significantly higher in group
      3 in comparison to the other groups. Multivariate subgroup analysis was conducted
      to determine mortality rates, with post-procedural highest creatinine >= 2 mg/dl
      and RBCPs >= 10 established as independent risk factors. CONCLUSIONS:
      Hemodynamically stable patients with no active hemorrhaging are shown to have
      good results with conservative treatment. We believe that endovascular methods
      should be used initially for hemodynamically unstable patients, while surgical
      treatment should be employed in cases where endovascular methods fail or
      abdominal compartment syndrome develops.

PMID- 29056996
TI  - Sex-related differences in clinical outcomes and quality of life after
      transcatheter aortic valve implantation for severe aortic stenosis.
AB  - INTRODUCTION: There are inconsistent data on the sex-related differences in
      clinical outcomes and quality of life (QoL) after transcatheter aortic valve
      implantation (TAVI). AIM: We sought to investigate sex-related differences in
      procedural, clinical and QoL outcomes of TAVI. MATERIAL AND METHODS: A total of
      101 consecutive patients undergoing TAVI were enrolled. Patients were stratified
      by gender. Baseline characteristics, procedural and long-term clinical outcomes
      as well as frailty and QoL indices (EQ-5D-3L questionnaire) were compared between
      women and men. RESULTS: Women represented 60.4% of the study population.
      Periprocedural risk measured with the Logistic EuroSCORE and STS scale was
      similar for women and men. There were no differences in 30-day or 12-month all
      cause mortality between groups (women vs. men: 9.8% vs. 12.5%; age-adjusted odds
      ratio (OR) (95% CI): 1.38 (0.39-4.94); 13.1% vs. 25.0%; age-adjusted OR (95% CI):
      2.51 (0.87-7.25)). Men were at higher risk of new onset atrial fibrillation at
      follow-up (1.6% vs. 17.5%; age-adjusted OR (95% CI): 14.61 (1.68-127.37)). In
      multivariable Cox regression analysis, a history of stroke/transient ischemic
      attack (TIA) (hazard ratio (HR)) (95% CI): 3.93 (1.39-11.07) and blood
      transfusion (HR (95% CI): 2.84 (1.06-7.63)) were identified as independent
      factors affecting 12-month mortality. No differences in QoL parameters were
      noted. CONCLUSIONS: The TAVI can be considered as an effective and safe treatment
      in high-risk patients with severe aortic stenosis, regardless of gender.

PMID- 29056995
TI  - Magnetic resonance imaging and clinical outcome in patients with symptomatic
      carotid artery stenosis after carotid artery revascularization.
AB  - INTRODUCTION: About 30% of patients with carotid artery stenosis (CAS) develop
      dementia after a cerebral ischemic event (CIE), and 20-50% suffer from CIE
      recurrence during 6 months. Carotid artery revascularization (CAR) may prevent
      CIE recurrence, at the cost of new microembolic lesions (MES). The impact of CAR
      on cognitive function is debatable. AIM: To assess functional and cognitive
      outcome, cerebral flow on transcranial Doppler (TCD) and brain magnetic resonance
      imaging (MRI) in patients with symptomatic CAS referred for CAR. MATERIAL AND
      METHODS: Twenty-two patients (aged 69.0 +/-7.2 y.o., 15 male) with recent CIE
      (21.9 +/-20.9 days to CAR) related to CAS of mean 89.8 +/-3.9% lumen reduction
      were prospectively evaluated with TCD, diffusion and perfusion MRI, Montreal
      Cognitive Assessment (MoCA), Mini Mental State Examination (MMSE), modified
      Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) 24
      h before, at 24-48 h and 1 month following CAR. RESULTS: New MES were found in 11
      (50%) subjects following CAR. CAR resulted in a significant increase of cerebral
      flow velocity in the middle and anterior cerebral arteries (p < 0.002 and p =
      0.003; respectively) and cerebral perfusion measured by time to peak (TTP) and
      mean transit time (MTT) (p = 0.0009 and p = 0.0002; respectively). Neurologic
      tests showed improvement in NIHSS (2.4 +/-1.6 to 1.5 +/-1.2, p = 0.003), mRS
      (from 1.3 +/-0.9 to 0.7 +/-0.9, p = 0.005), and MMSE (26.7 +/-2.2 to 27.6 +/-2.3,
      p = 0.019) at 1 month, while similar MoCA scores were observed before and 1 month
      after CAR (23.4 +/-3.3 vs. 24.1 +/-3.7, p = 0.136). CONCLUSIONS: Improvement of
      cerebral flow and perfusion and functional outcome, as well as at least no
      cognitive decline, is observed after CAR for symptomatic CAS.

PMID- 29056997
TI  - Efficacy and safety of cryoballoon ablation versus radiofrequency catheter
      ablation in atrial fibrillation: an updated meta-analysis.
AB  - INTRODUCTION: Cryoballoon ablation (CBA) and irrigated radiofrequency catheter
      ablation (RFCA) are the main treatments for drug-refractory symptomatic atrial
      fibrillation (AF). AIM: To compare the efficacy and safety between CBA and RFCA
      for the treatment of AF. MATERIAL AND METHODS: We searched the Embase and Medline
      databases for clinical studies published up to December 2016. Studies that
      satisfied our predefined inclusion criteria were included. RESULTS: After
      searching through the literature in the two major databases, 20 studies with a
      total of 9,141 patients were included in our study. The CBA had a significantly
      shorter procedure time (weighted mean difference (WMD) -30.38 min; 95% CI: -46.43
      to -14.33, p = 0.0002) and non-significantly shorter fluoroscopy time (WMD -3.18
      min; 95% CI: -6.43 to 0.07, p = 0.06) compared with RFCA. There was no difference
      in freedom from AF between CBA and RFCA (CBA 78.55% vs. RFCA 83.13%, OR = 1.15,
      95% CI: 0.95-1.39, p = 0.14). The CBA was associated with a high risk of
      procedure-related complications (CBA 9.02% vs. RFCA 6.56%, OR = 1.56, 95% CI:
      1.05-2.31, p = 0.03), especially phrenic nerve paralysis (PNP, OR = 10.72, 95%
      CI: 5.59-20.55, p < 0.00001). The risk of pericardial effusions/cardiac tamponade
      was low in the CBA group (CBA 1.05% vs. RFCA 1.86%, OR = 0.62, 95% CI: 0.41-0.93,
      p = 0.02). CONCLUSIONS: For AF, CBA was as effective as RFCA. However, CBA had a
      shorter procedure time and a non-significantly shorter fluoroscopy time, a
      significantly high risk of PNP and a low incidence of pericardial
      effusions/cardiac tamponade compared with RFCA.

PMID- 29056998
TI  - Nonalcoholic fatty liver disease as a predictor of atrial fibrillation: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Numerous epidemiologic studies have investigated the link between
      nonalcoholic fatty liver disease (NAFLD) and long-term atrial fibrillation (AF)
      risk, but the results are surprisingly conflicting. AIM: Therefore, we
      systematically reviewed all published studies assessing the risk of AF in
      patients with NAFLD and conducted a meta-analysis. MATERIAL AND METHODS: We
      performed a literature search using PubMed, EMBASE and Cochrane Library databases
      in February 2017 with no restrictions. Two cohort studies and two cross-sectional
      studies were identified, involving a total of 5150 subjects (NAFLD: 1655;
      controls: 3495) in this meta-analysis. Data from selected studies were extracted
      and a meta-analysis was performed using a random effects model. RESULTS:
      Nonalcoholic fatty liver disease patients had a significantly higher risk of AF
      compared to controls (relative risk (RR): 2.61; 95% confidence interval (CI):
      1.34-5.06, p = 0.00; I2 = 52.5%, p = 0.097). In a further analysis stratified by
      presence of type 2 diabetes, the increased risk was present predominantly in
      patients with type 2 diabetes (RR = 5.10; 95% CI: 2.43-10.7, p < 0.001; I2 = 0, p
      = 0.958). However, subjects without type 2 diabetes were at slightly increased
      risk of AF but the relative risk did not reach statistical significance (RR =
      1.68; 95% CI: 0.99-2.82, p = 0.05; I2 = 0, p = 0.461). CONCLUSIONS: Our meta
      analysis suggested that ultrasound-diagnosed NAFLD patients have a significantly
      higher risk for AF after adjustment for numerous important clinical risk factors
      for AF. These results need to be confirmed in large prospective studies.

PMID- 29056999
TI  - Assessment of cognitive functions and quality of life in patients scheduled for
      transcatheter aortic valve implantation: a pilot study.

PMID- 29057000
TI  - Fusion of real-time 3D transesophageal echocardiography and cardiac fluoroscopy
      imaging in transapical catheter-based mitral paravalvular leak closure.

PMID- 29057001
TI  - 3D image fusion for live guidance of stent implantation in aortic coarctation -
      magnetic resonance imaging and computed tomography image overlay enhances
      interventional technique.

PMID- 29057002
TI  - Tricuspid paravalvular leak closure with a paravalvular leak device.

PMID- 29057003
TI  - Stenting of narrow pulmonary artery banding in a patient with univentricular
      heart.

PMID- 29057004
TI  - Combined strategy of Waterston shunt percutaneous occlusion and medical treatment
      with sildenafil for management of pulmonary hypertension in an adult patient with
      corrected tetralogy of Fallot.

PMID- 29057005
TI  - Pulmonary vein isolation in a patient with atrial fibrillation and a filter in
      the inferior vena cava.

PMID- 29057006
TI  - Risk factors for self-report of not receiving an HIV test among adolescents in
      NYC with a history of sexual intercourse, 2013 YRBS.
AB  - The Centers for Disease Control and Prevention (CDC) has previously recommended
      that all adolescents undergo HIV testing in the United States (US). Despite these
      recommendations, national HIV testing among US adolescents has remained low. This
      study estimated the prevalence of and identified risk factors for not receiving
      an HIV test among adolescents with a history of sexual intercourse in New York
      City (NYC), an urban area that has been greatly impacted by the HIV epidemic.
      Cross-sectional data on 1,199 NYC high school students who completed the 2013 NYC
      Youth Risk Behavior Survey were used. Modified Poisson regression models were
      used to assess whether demographic factors, alcohol/drug use, and sexual
      behaviors were associated with self-report of lack of HIV testing. In the
      weighted study population, about 72% were >=16 years old, approximately 35% were
      African American, and nearly half were male. Sixty percent reported no history of
      HIV testing. In adjusted analyses, younger age, male gender, White
      race/ethnicity, heroin use, as well as reporting one prior sexual partner were
      significantly and positively associated with no prior history of HIV testing. Our
      findings suggest that among NYC adolescents with a history of sexual intercourse,
      the prevalence of HIV testing is low. HIV testing may have been low in part
      because of limited experience with current screening guidelines among clinicians.
      Furthermore, many of the adolescents identified as being more likely to not be
      tested, may have not been screened because of inadequate knowledge about HIV, a
      low perceived HIV risk, or an unstable lifestyle. Therefore, to increase HIV
      testing among NYC adolescents, interventions that enhance HIV knowledge among
      adolescents as well as interventions that promote review and application of
      current screening guidelines among clinicians should be implemented in NYC.
      Educational interventions should especially be targeted at the adolescents
      identified in this study.

PMID- 29057007
TI  - The Architecture of Recovery: Two Kinds of Housing Assistance for Chronic
      Homeless Persons with Substance Use Disorders.
AB  - PURPOSE: Roughly half a million persons in the United States are homeless on any
      given night and over a third of those individuals have significant alcohol/other
      drug (AOD) problems. Many are chronically homeless and in need of assistance for
      a variety of problems. However, the literature on housing services for this
      population has paid limited attention to comparative analyses contrasting
      different approaches. APPROACH: We examined the literature on housing models for
      homeless persons with AOD problems and critically analyzed how service settings
      and operations aligned with service goals. FINDINGS: We found two predominant
      housing models that reflect different service goals: Sober Living Houses (SLHs)
      and Housing First (HF). SLHs are communally based living arrangements that draw
      on the principles of Alcoholics Anonymous. They emphasize a living environment
      that promotes abstinence and peer support for recovery. HF is based on the
      premise that many homeless persons with substance abuse problems will reject
      abstinence as a goal. Therefore, the HF focus is providing subsidized or free
      housing and optional professional services for substance abuse, psychiatric
      disorders and other problems. PRACTICAL IMPLICATIONS: If homeless service
      providers are to develop comprehensive systems for homeless persons with AOD
      problems, they need to consider important contrasts in housing models, including
      definitions of "recovery," roles of peer support, facility management, roles for
      professional service, and the architectural designs that support the mission of
      each type of housing. ORIGINALITY: This paper is the first to consider distinct
      consumer choices within homeless service systems and provide recommendations to
      improve each based upon an integrated analysis that considers how architecture
      and operations align with service goals.

PMID- 29057008
TI  - Experimental evaluation of the resolution improvement provided by a silicon PET
      probe.
AB  - A high-resolution PET system, which incorporates a silicon detector probe into a
      conventional PET scanner, has been proposed to obtain increased image quality in
      a limited region of interest. Detailed simulation studies have previously shown
      that the additional probe information improves the spatial resolution of the
      reconstructed image and increases lesion detectability, with no cost to other
      image quality measures. The current study expands on the previous work by using a
      laboratory prototype of the silicon PET-probe system to examine the resolution
      improvement in an experimental setting. Two different versions of the probe
      prototype were assessed, both consisting of a back-to-back pair of 1-mm thick
      silicon pad detectors, one arranged in 32 * 16 arrays of 1.4 mm * 1.4 mm pixels
      and the other in 40 * 26 arrays of 1.0 mm * 1.0 mm pixels. Each detector was read
      out by a set of VATAGP7 ASICs and a custom-designed data acquisition board which
      allowed trigger and data interfacing with the PET scanner, itself consisting of
      BGO block detectors segmented into 8 * 6 arrays of 6 mm * 12 mm * 30 mm crystals.
      Limited-angle probe data was acquired from a group of Na-22 point-like sources in
      order to observe the maximum resolution achievable using the probe system. Data
      from a Derenzo-like resolution phantom was acquired, then scaled to obtain
      similar statistical quality as that of previous simulation studies. In this case,
      images were reconstructed using measurements of the PET ring alone and with the
      inclusion of the probe data. Images of the Na-22 source demonstrated a resolution
      of 1.5 mm FWHM in the probe data, the PET ring resolution being approximately 6
      mm. Profiles taken through the image of the Derenzo-like phantom showed a clear
      increase in spatial resolution. Improvements in peak-to-valley ratios of 50% and
      38%, in the 4.8 mm and 4.0 mm phantom features respectively, were observed, while
      previously unresolvable 3.2 mm features were brought to light by the addition of
      the probe. These results support the possibility of improving the image
      resolution of a clinical PET scanner using the silicon PET-probe.

PMID- 29057009
TI  - Behavioral comparisons in Autism Spectrum Disorder and Developmental Coordination
      Disorder: A systematic literature review.
AB  - BACKGROUND: Autism Spectrum Disorder (ASD) and Developmental Coordination
      Disorder (DCD) are developmental disorders that, since the DSM-5, can be
      diagnosed as co-occurring conditions. While some recent studies suggest that ASD
      and DCD have similar traits, others show clear behavioral distinctions between
      the two conditions. By gathering all studies that included (1) an ASD group and a
      DCD group, (2) an ASD+DCD group and a DCD group, or (3) ASD, ASD+DCD, and DCD
      groups, we aimed to identify similarities and differences in behaviors between
      the two disorders. METHOD: We used a systematic search of PubMed (1946 -), Scopus
      (1970 -), PsycINFO (via EBSCO, 1600 -), CINAHL (via EBSCO, 1937 -), SportDiscus
      (via EBSCO, 1985 -), and WorldCat (via FirstSearch) in addition to reference list
      and author name searching PubMed, Scopus, PsycINFO, CINAHL, SportDiscus, and
      WorldCat to identify original studies that met the following criteria: (1) an ASD
      group and a DCD group, (2) an ASD+DCD group and a DCD group, or (3) ASD, ASD+DCD,
      and DCD groups. RESULTS: From the 1,598 articles screened, 11 were included in
      the qualitative analysis. The articles included reported more differences than
      similarities in individuals with ASD and DCD, with clear distinctions for working
      memory ability, gestural performance, grip selection, and cortical thickness.
      Only two studies reported similarities in face processing abilities and perceived
      competence, and the interventional studies showed group similarities in behavior
      improvement, such as intelligence and attention. CONCLUSIONS: Based on the
      articles reviewed, we conclude that while DCD and ASD share some behavioral
      symptoms, the symptom profiles of each disorder are unique and separable. We
      recommend that the evaluation of potential DCD in individuals with ASD be
      performed systematically and thoroughly, so as to distinguish this co-occurring
      condition from sensorimotor symptoms associated with ASD.

PMID- 29057010
TI  - Associations between Lifestyle Factors and Parkinson's Disease in an Urban Sri
      Lankan Clinic Study.
AB  - BACKGROUND: Associations between certain environmental and lifestyle factors and
      Parkinson's disease (PD) have been reported in several studies, but information
      on these factors and Parkinson's Disease (PD) in South Asia, is limited.
      OBJECTIVE: To determine associations between lifestyle factors and PD in an urban
      clinic-based study in Sri Lanka. METHODS: In this case-control study, demographic
      and lifestyle factor data (including diet, coffee/tea drinking, smoking, alcohol
      status) was collected from an unselected cohort of PD patients and age and gender
      matched controls attending clinics in Greater Colombo, Sri Lanka. Associations
      between lifestyle factors and PD status were assessed using Logistic Regression
      analysis, while links with age of PD onset were explored with Kaplan Meier and
      Cox Regression survival analyses. Results with p<0.05 were considered to be
      statistically significant. FINDINGS: Of 229 patients with parkinsonism, 144 had
      Idiopathic PD using standard diagnostic criteria. Controls numbered 102. Coffee
      drinkers and smokers were significantly less likely to have PD (coffee, p<0.001;
      Odds Ratio (OR)=0.264; smoking, p=0.043; OR=0.394). Coffee drinkers were older at
      PD onset (p<0.001). Similar trends seen with tea drinking were not statistically
      significant. CONCLUSIONS: This is the first formal study of PD and these
      lifestyle factors in South Asia. It demonstrates an inverse association between
      coffee drinking, smoking and PD, and an association between coffee drinking and
      later age of PD onset. This is in line with other studies done worldwide,
      suggesting biological associations with global relevance.

PMID- 29057011
TI  - Selective monophosphorylation of chitosan via phosphorus oxychloride.
AB  - Chitosan was selectively monophosphorylated via reaction with phosphorus
      oxychloride (POCl3) to enhance water solubility while avoiding polyphosphate
      formation. The use of POCl3 resulted in negligible product degradation (i.e.,
      breakdown of O-glycosidic bonds) even after a 3 d reaction period (<5% weight
      loss). X-ray photoelectron spectroscopy (XPS) characterization of the POCl3
      phosphorylated chitosan (P-chitosan) revealed a phosphorus to nitrogen (P/N)
      atomic ratio of 0.30. Phosphorus-31 nuclear magnetic resonance (31P NMR)
      spectroscopy verified the monophosphorylation of chitosan's primary and secondary
      alcohols, and primary amines. The calcium chelation efficiency for the
      phosphorylated product approached 0.05 mg Ca2+ per mg of P-chitosan as measured
      by inductively coupled plasma-optical emission spectrometry (ICP-OES), indicating
      improved chelation over native chitosan. This selective monophosphorylation
      approach proved useful for modifying other biopolymers, including cellulose and
      alginate.

PMID- 29057012
TI  - One-pot blue-light triggered tough interpenetrating polymeric network (IPN) using
      CuAAC and methacrylate reactions.
AB  - An interpenetrating polymeric network (IPN) is formed in a one-pot blue-light
      activated scheme, where the step- and chain- growth polymerizations of the CuAAC
      and methacrylate reactions, respectively, are simultaneously triggered but
      proceed sequentially. The glassy IPN is polymerized under ambient conditions and
      is able to withstand high strain before failure owing to its significantly
      enhanced toughness. Additionally, this material exhibits shape memory attributes
      with readily tunable mechanical properties at high temperature.

PMID- 29057014
TI  - Eudaimonic well-being, inequality, and health: Recent findings and future
      directions.
AB  - The theoretical and philosophical underpinnings of a eudaimonic model of well
      being are examined and its empirical translation into distinct dimensions of well
      being is described. Empirical findings have documented aging declines in
      eudaimonic well-being, but there is considerable variability within age groups.
      Among older adults who remain purposefully engaged, health benefits (reduced
      morbidity, extended longevity) have been documented. Eudaimonic well-being also
      appears to offer a protective buffer against increased health risk among the
      educationally disadvantaged. Neural and genetic mechanisms that may underlie
      eudaimonic influences on health are briefly noted, and interventions designed to
      promote eudaimonic well-being are sketched. Needed future research directions
      include addressing problems of unjust societies wherein greed among privileged
      elites may be a force compromising the eudaimonic well-being of those less
      privileged. Alternatively, and more positive in focus, is the need to better
      understand the role of the arts, broadly defined, in promoting eudaimonic well
      being across all segments of society.

PMID- 29057013
TI  - Brain Activity in Self- and Value-Related Regions in Response to Online
      Antismoking Messages Predicts Behavior Change.
AB  - In this study, we combined approaches from media psychology and neuroscience to
      ask whether brain activity in response to online antismoking messages can predict
      smoking behavior change. In particular, we examined activity in subregions of the
      medial prefrontal cortex linked to self- and value-related processing, to test
      whether these neurocognitive processes play a role in message-consistent behavior
      change. We observed significant relationships between activity in both brain
      regions of interest and behavior change (such that higher activity predicted a
      larger reduction in smoking). Furthermore, activity in these brain regions
      predicted variance independent of traditional, theory-driven self-report metrics
      such as intention, self-efficacy, and risk perceptions. We propose that valuation
      is an additional cognitive process that should be investigated further as we
      search for a mechanistic explanation of the relationship between brain activity
      and media effects relevant to health behavior change.

PMID- 29057015
TI  - New developments in the pathology of malignant lymphoma: a review of the
      literature published from May to August 2017.

PMID- 29057016
TI  - What Would I Know About Mercy? Faith and Optimistic Expectancies Among African
      Americans.
AB  - A small body of research has begun to explore the association between faith and
      optimism among African Americans. However, missing from the extant work is an
      examination of the extent to which traditional indices of religious commitment
      work together with beliefs about God to shape optimism. The present study
      examines the utility of indices of social location, religious commitment (i.e.,
      early and current religious service attendance, subjective religiosity), belief
      about the quality of one's relationship with God (i.e., a belief that one is
      connected to a loving God), and beliefs about being the recipient of divine
      forgiveness for predicting dispositional optimism among a sample of community
      residing African American adults (N = 241). Age, subjective religiosity, and
      organizational religiosity were positively related to optimism in bivariate
      analyses. Hierarchical regression analyses demonstrated a significant association
      between age, subjective religiosity, and optimism; however, those associations
      were eliminated once relationship with God and belief in one's forgiveness by God
      were entered into the model. Only belief in God's love predicted optimism in
      multivariate analyses. Serial mediation analyses revealed that beliefs about the
      quality of one's relationship with God and belief in divine forgiveness fully
      mediated the relationship between subjective religiosity and optimism, but that
      the relationship is driven largely by relationship with God. Implications of
      these findings are discussed.

PMID- 29057017
TI  - The shape of change in perceived stress, negative affect, and stress sensitivity
      during mindfulness-based stress reduction.
AB  - Both daily stress and the tendency to react to stress with heightened levels of
      negative affect (i.e., stress sensitivity) are important vulnerability factors
      for adverse mental health outcomes. Mindfulness-based stress reduction (MBSR) may
      help to reduce perceived daily stress and stress sensitivity. The purpose of this
      study was to examine how change in perceived stress, negative affect (NA), and
      the decoupling between perceived stress and NA evolved over the course of a MBSR
      program, without making any a priori assumptions on the shape of change. Seventy
      one adults from the general population participating in MBSR provided daily diary
      assessments of perceived stress and NA during MBSR. The time-varying effect model
      (TVEM) indicated that perceived stress and NA decreased in a linear fashion
      rather than in a non-linear fashion, both as a function of time and as a function
      of the cumulative number of days of mindfulness practice. Both TVEM and
      multilevel growth modeling showed that the association between perceived stress
      and NA did not decrease over the course of MBSR. The findings support the
      hypothesis that MBSR reduces NA and also reduces the extent to which individuals
      perceive their days as stressful. Also, the results suggest that there is a dose
      response relationship between the amount of mindfulness practice and reductions
      in daily stress and NA.

PMID- 29057019
TI  - A Summary of a Cochrane Review: Yoga treatment for chronic non-specific low back
      pain.

PMID- 29057018
TI  - Influence of Electromechanical Activity on Cardiac Differentiation of Mouse
      Embryonic Stem Cells.
AB  - During differentiation, mouse embryonic stem cell-derived cardiomyocytes (mESC
      CMs) receive electromechanical cues from spontaneous beating. Therefore,
      promoting electromechanical activity via electrical pacing or suppressing it by
      drug treatment might affect the cellular functional development. Electrical
      pacing was applied to confluent monolayers of mESC-CMs during late-stage
      differentiation (days 16-18). Alternatively, spontaneous contraction was
      suppressed by (a) blocking ion currents with CsCl (HCN channel), trazodone (T
      type Ca2+ channel), or both CsCl and trazodone on days 11-18; or (b) applying
      blebbistatin (excitation-contraction uncoupler) on days 11-14.
      Electrophysiological properties and gene expression were examined on day 19 and
      18, respectively. Optical mapping revealed no significant difference in
      conduction velocity (CV)in paced vs. non-pacedmonolayers, nor were there
      significant changes in gene expression of connexin-43, Na-Ca exchanger (NCX), or
      myosin heavy chain (MHC). However, CV variability among differentiation batches
      and CV heterogeneity within individual monolayers were significantly lower in
      paced mESC-CMs. Alternatively, while the four drug treatments suppressed
      contraction with varying degrees (up to complete inhibition), there was no
      significant difference in CV for any of the treatments compared with controls.
      Trazodone treatment significantly reduced CV variability as compared to controls,
      whereas CsCl treatment significantly reduced CV heterogeneity. Distinct changes
      in gene expression of connexin-43, MHC, HCNl, Cav3.1/3.2 were not observed.
      Electrical pacing, but not suppression of spontaneous contraction, during late
      stage differentiation reduces the intrinsic variability of CV among
      differentiation batches and across individual monolayers, which can be beneficial
      in the application of ESCs for myocardial tissue repair.

PMID- 29057020
TI  - Common mistakes when using plant names and how to avoid them.

PMID- 29057021
TI  - Focus on overview of innovative materials for energy.

PMID- 29057022
TI  - Effect of slurry composition on the chemical mechanical polishing of thin diamond
      films.
AB  - Nanocrystalline diamond (NCD) thin films grown by chemical vapour deposition have
      an intrinsic surface roughness, which hinders the development and performance of
      the films' various applications. Traditional methods of diamond polishing are not
      effective on NCD thin films. Films either shatter due to the combination of wafer
      bow and high mechanical pressures or produce uneven surfaces, which has led to
      the adaptation of the chemical mechanical polishing (CMP) technique for NCD
      films. This process is poorly understood and in need of optimisation. To compare
      the effect of slurry composition and pH upon polishing rates, a series of NCD
      thin films have been polished for three hours using a Logitech Ltd. Tribo CMP
      System in conjunction with a polyester/polyurethane polishing cloth and six
      different slurries. The reduction in surface roughness was measured hourly using
      an atomic force microscope. The final surface chemistry was examined using X-ray
      photoelectron spectroscopy and a scanning electron microscope. It was found that
      of all the various properties of the slurries, including pH and composition, the
      particle size was the determining factor for the polishing rate. The smaller
      particles polishing at a greater rate than the larger ones.

PMID- 29057023
TI  - Focus on advanced nanoprocessing and applications in sensorics.

PMID- 29057024
TI  - Intermetallic compounds in 3D integrated circuits technology: a brief review.
AB  - The high performance and downsizing technology of three-dimensional integrated
      circuits (3D-ICs) for mobile consumer electronic products have gained much
      attention in the microelectronics industry. This has been driven by the
      utilization of chip stacking by through-Si-via and solder microbumps. Pb-free
      solder microbumps are intended to replace conventional Pb-containing solder
      joints due to the rising awareness of environmental preservation. The use of low
      volume solder microbumps has led to crucial constraints that cause several
      reliability issues, including excessive intermetallic compounds (IMCs) formation
      and solder microbump embrittlement due to IMCs growth. This article reviews
      technologies related to 3D-ICs, IMCs formation mechanisms and reliability issues
      concerning IMCs with Pb-free solder microbumps. Finally, future outlook on the
      potential growth of research in this area is discussed.

PMID- 29057027
TI  - DISCUSSION OF "FIBER DIRECTION ESTIMATION IN DIFFUSION MRI".

PMID- 29057025
TI  - Dye-sensitized photocatalyst for effective water splitting catalyst.
AB  - Renewable hydrogen production is a sustainable method for the development of next
      generation energy technologies. Utilising solar energy and photocatalysts to
      split water is an ideal method to produce hydrogen. In this review, the
      fundamental principles and recent progress of hydrogen production by artificial
      photosynthesis are reviewed, focusing on hydrogen production from photocatalytic
      water splitting using organic-inorganic composite-based photocatalysts.

PMID- 29057026
TI  - Hierarchical nanoporous metals as a path toward the ultimate three-dimensional
      functionality.
AB  - Nanoporous metals prepared via dealloying or selective leaching of solid solution
      alloys and compounds represent an emerging class of materials. They possess a
      three-dimensional (3D) structure of randomly interpenetrating ligaments/nanopores
      with sizes between 5 nm and several tens of micrometers, which can be tuned by
      varying their preparation conditions (such as dealloying time and temperature) or
      additional thermal coarsening. As compared to other nanostructured materials,
      nanoporous metals have many advantages, including their bicontinuous structure,
      tunable pore sizes, bulk form, good electrical conductivity, and high structural
      stability. Therefore, nanoporous metals represent ideal 3D materials with
      versatile functionality, which can be utilized in various fields. In this review,
      we describe the recent applications of nanoporous metals in molecular detection,
      catalysis, 3D graphene synthesis, hierarchical pore formation, and additive
      manufacturing (3D printing) together with our own achievements in these areas.
      Finally, we discuss possible ways of realizing the ultimate 3D functionality
      beyond the scope of nanoporous metals.

PMID- 29057028
TI  - Regiospecific Nucleation and Growth of Silane Coupling Agent Droplets onto
      Colloidal Particles.
AB  - Nucleation-and-growth processes are used extensively in the synthesis of
      spherical colloids, and more recently regiospecific nucleation-and-growth
      processes have been exploited to prepare more complex colloids such as patchy
      particles. We demonstrate that surface geometry alone can be made to play the
      dominant role in determining the final particle geometry in such syntheses,
      meaning that intricate chemical surface patternings are not required. We present
      a synthesis method for "lollipop"-shaped colloidal heterodimers (patchy
      particles), combining a recently published nucleation-and-growth technique with
      our recent findings that particle geometry influences the locus of droplet
      adsorption onto anisotropic template particles. Specifically, 3
      methacryloxypropyl trimethoxysilane (MPTMS) is nucleated and grown onto bullet
      shaped and nail-shaped colloids. The shape of the template particle can be chosen
      such that the MPTMS adsorbs regiospecifically onto the flat ends. In particular,
      we find that particles with a wider base increase the range of droplet volumes
      for which the minimum in the free energy of adsorption is located at the flat end
      of the particle compared with bullet-shaped particles of the same aspect ratio.
      We put forward an extensive analysis of the synthesis mechanism and
      experimentally determine the physical properties of the heterodimers, supported
      by theoretical simulations. Here we numerically optimize, for the first time, the
      shape of finite-sized droplets as a function of their position on the rod-like
      silica particle surface. We expect that our findings will give an impulse to
      complex particle creation by regiospecific nucleation and growth.

PMID- 29057029
TI  - Transthyretin Cardiac Amyloidosis in Older Adults: Optimizing Cardiac Imaging to
      the Corresponding Diagnostic and Management Goal.
AB  - PURPOSE OF REVIEW: Transthyretin cardiac amyloidosis is increasingly recognized
      as an important cause of heart failure in older adults. Many cardiac imaging
      modalities have evolved to evaluate transthyretin cardiac amyloidosis and include
      2D echocardiography with tissue Doppler and speckle-strain imaging, nuclear
      scintigraphy, cardiac magnetic resonance imaging, and positron emission
      tomography. The purpose of this review is to highlight the optimal selection of
      advanced cardiac imaging techniques with corresponding diagnostic goals including
      raising suspicion, making an early diagnosis, and subtyping transthyretin cardiac
      amyloid, as well as management goals including assessment of ventricular
      impairment, prognosticating, and monitoring disease progression. Potential
      benefits of optimizing cardiac imaging in the elderly patient with transthyretin
      cardiac amyloidosis may include enhanced and earlier diagnosis and refined long
      term management. RECENT FINDINGS: Advances in cardiac imaging techniques are
      changing diagnostic and management algorithms for transthyretin cardiac
      amyloidosis. SUMMARY: With a new era of novel therapeutics, enhanced recognition,
      and earlier diagnosis approaching, selecting the appropriate non-invasive cardiac
      imaging modality will be essential for optimal care in the elderly patient with
      transthyretin cardiac amyloidosis.

PMID- 29057030
TI  - Substance Use in Rural Central Appalachia: Current Status and Treatment
      Considerations.
AB  - The burden of substance use and especially the unmatched rates of overdoses in
      rural Central Appalachia highlight the need for innovative approaches to curb the
      initiation to drug misuse and to address current substance use disorders.
      Effective substance use interventions involve a thorough understanding of the
      region. In Central Appalachia, many of the barriers to treatment are shared with
      other rural and impoverished areas, including a lack of access to health care and
      lack of health care providers with specialized training. Parts of Appalachia also
      present their own considerations, including the challenges of fostering trust and
      encouraging treatment-seeking in communities with dense, long-term, place-based
      social and family networks. Current policies and interventions for substance use
      have been largely inadequate in the region, as evidenced by continued increases
      in substance use and substance-related deaths, especially related to nonmedical
      prescription drug use and increasing heroin use. The authors discuss ways in
      which rural life, poverty, identity, and values in Appalachia have influenced
      substance use and treatment and propose strategies and interventions to improve
      outcomes.

PMID- 29057031
TI  - Plausibility Judgments of Atypical Symptoms Across Cultures: an Explorative Study
      Among Western and Non-Western Experts.
AB  - Symptom validity tests (SVTs) are predicated on the assumption that
      overendorsement of atypical symptoms flags symptom exaggeration (i.e.,
      questionable symptom validity). However, few studies have explored how
      practitioners from different cultural backgrounds evaluate such symptoms. We
      asked professionals working in Western (n = 56) and non-Western countries (n =
      37) to rate the plausibility of uncommon symptoms taken from the Structured
      Inventory of Malingered Symptomatology (SIMS), dissociative symptoms from the
      Dissociative Experience Scale (DES-T), and standard symptoms (e.g., anxiety,
      depression) from the Brief Symptom Inventory-18 (BSI-18). Western and non-Western
      experts gave similar plausibility ratings to atypical, dissociative, and standard
      symptoms: both groups judged BSI-18 symptoms as significantly more plausible than
      either dissociative or atypical symptoms, while the latter two categories did not
      differ. Our results suggest that the strategy to detect symptom exaggeration by
      exploring overendorsement of atypical items might work in a non-western context
      as well.

PMID- 29057032
TI  - Decreased Drinking and Alcoholics Anonymous are Associated with Different
      Dimensions of Spirituality.
AB  - : Alcoholics Anonymous (AA) is a spiritual program and involvement in it has been
      associated with increases in spirituality. Some who pursue recovery outside AA
      also use spirituality for support. Decreasing drinking without AA involvement
      might result in spiritual change, but this has not been explored in previous
      research. This study investigates drinking and AA behavior to determine their
      association with seven dimensions of subsequent spirituality. METHODS: A 30-month
      panel study recruited 364 individuals with alcohol dependence. Multilevel models
      examined drinking and AA at six months as predictors of both the levels and
      trajectories of seven dimensions of spirituality assessed five times over 6 - 30
      months. RESULTS: Controlling for AA involvement, less drinking was associated
      with higher levels of purpose in life, self-forgiveness, and spiritual/religious
      practices. Controlling for drinking, greater AA involvement was associated with
      higher levels of positive religious coping, daily spiritual experiences,
      forgiveness of others, and spiritual/religious practices. Neither AA nor drinking
      predicted trajectories of spirituality. Data visualizations identified a pattern
      of elevated purpose in life and self-forgiveness among individuals who were
      abstinent and among individuals who drank less intensely. CONCLUSIONS: Reduced
      drinking influenced aspects of spirituality that have been shown to respond to
      experience and maturation. AA was associated with aspects of spirituality
      embedded in the 12 steps which have been shown to be responsive to learning and
      modeling. This knowledge has the potential to inform decisions about recovery
      options, and contributes to theoretical understandings of the nature of spiritual
      change over the course of addiction recovery.

PMID- 29057033
TI  - Polydatin Prevents Methylglyoxal-Induced Apoptosis through Reducing Oxidative
      Stress and Improving Mitochondrial Function in Human Umbilical Vein Endothelial
      Cells.
AB  - Methylglyoxal (MGO), an active metabolite of glucose, has been reported to induce
      vascular cell apoptosis in diabetic complication. Polydatin (PD), a small natural
      compound from Polygonum cuspidatum, has a number of biological functions, such as
      antioxidative, anti-inflammatory, and nephroprotective properties. However, the
      protective effects of PD on MGO-induced apoptosis in endothelial cells remain to
      be elucidated. In this study, human umbilical vein endothelial cells (HUVECs)
      were used to explore the effects of PD on MGO-induced cell apoptosis and the
      possible mechanism involved. HUVECs were pretreated with PD for 2 h, followed by
      stimulation with MGO. Then cell apoptosis, reactive oxygen species (ROS)
      generation, mitochondrial membrane potential (MMP) impairment, mitochondrial
      morphology alterations, and Akt phosphorylation were assessed. The results
      demonstrated that PD significantly prevented MGO-induced HUVEC apoptosis. PD
      pretreatment also significantly inhibited MGO-induced ROS production, MMP
      impairment, mitochondrial morphology changes, and Akt dephosphorylation. These
      results and the experiments involving N-acetyl cysteine (antioxidant),
      Cyclosporin A (mitochondrial protector), and LY294002 (Akt inhibitor) suggest
      that PD prevents MGO-induced HUVEC apoptosis, at least in part, through
      inhibiting oxidative stress, maintaining mitochondrial function, and activating
      Akt pathway. All of these data indicate the potential application of PD for the
      treatment of diabetic vascular complication.

PMID- 29057034
TI  - Oxidative Stress and Endometriosis: A Systematic Review of the Literature.
AB  - Endometriosis is one of the most common gynaecologic diseases in women of
      reproductive age. It is characterized by the presence of endometrial tissue
      outside the uterine cavity. The women affected suffer from pelvic pain and
      infertility. The complex etiology is still unclear and it is based on three main
      theories: retrograde menstruation, coelomic metaplasia, and induction theory.
      Genetics and epigenetics also play a role in the development of endometriosis.
      Recent studies have put the attention on the role of oxidative stress, defined as
      an imbalance between reactive oxygen species (ROS) and antioxidants, which may be
      implicated in the pathophysiology of endometriosis causing a general inflammatory
      response in the peritoneal cavity. Reactive oxygen species are intermediaries
      produced by normal oxygen metabolism and are inflammatory mediators known to
      modulate cell proliferation and to have deleterious effects. A systematic review
      was performed in order to clarify the different roles of oxidative stress and its
      role in the development of endometriosis. Several issues have been investigated:
      iron metabolism, oxidative stress markers (in the serum, peritoneal fluid,
      follicular fluid, peritoneal environment, ovarian cortex, and eutopic and ectopic
      endometrial tissue), genes involved in oxidative stress, endometriosis-associated
      infertility, and cancer development.

PMID- 29057036
TI  - Effects of Chimonanthus nitens Oliv. Leaf Extract on Glycolipid Metabolism and
      Antioxidant Capacity in Diabetic Model Mice.
AB  - The paper investigated the antihyperglycemic and antihyperlipidemic efficacy and
      antioxidant capacity of Chimonanthus nitens Oliv. leaf extract (COE) in
      combination of high-glucose-fat diet-fed and streptozotocin-induced diabetic
      model mice. Various physiological indexes in diabetic model mice were well
      improved especially by oral administration of high dose of COE; the results were
      listed as follows. Fast blood glucose (FBG) level and serum triglyceride (TC),
      total cholesterol (TG), low-density lipoprotein cholesterol (LDLC), and
      malondialdehyde (MDA) as well as MDA in liver were significantly reduced; fasting
      serum insulin (FINS) and insulin sensitivity index (ISI) were both increased;
      high-density lipoprotein cholesterol (HDLC) in serum was significantly increased;
      total antioxidant capacity (T-AOC), activities of superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), and catalase (CAT) in serum and liver were
      apparently enhanced; liver coefficient (LC), liver transaminase, and alkaline
      phosphatase (ALP) were decreased. Furthermore, pancreas islets and liver in
      diabetic model mice showed some extend of improvement in morphology and function
      after 4 weeks of COE treatment. In consequence, COE was advantageous to regulate
      glycolipid metabolism and elevate antioxidant capacity in diabetic model mice.
      Thus, the present study will provide a scientific evidence for the use of COE in
      the management of diabetes and its related complications.

PMID- 29057035
TI  - Sepsis-Induced Cardiomyopathy: Oxidative Implications in the Initiation and
      Resolution of the Damage.
AB  - Cardiac dysfunction may complicate the course of severe sepsis and septic shock
      with significant implications for patient's survival. The basic pathophysiologic
      mechanisms leading to septic cardiomyopathy have not been fully clarified until
      now. Disease-specific treatment is lacking, and care is still based on supportive
      modalities. Septic state causes destruction of redox balance in many cell types,
      cardiomyocytes included. The production of reactive oxygen and nitrogen species
      is increased, and natural antioxidant systems fail to counterbalance the
      overwhelming generation of free radicals. Reactive species interfere with many
      basic cell functions, mainly through destruction of protein, lipid, and nucleic
      acid integrity, compromising enzyme function, mitochondrial structure and
      performance, and intracellular signaling, all leading to cardiac contractile
      failure. Takotsubo cardiomyopathy may result from oxidative imbalance. This
      review will address the multiple aspects of cardiomyocyte bioenergetic failure in
      sepsis and discuss potential therapeutic interventions.

PMID- 29057037
TI  - Anti-inflammatory Silent Agonists.
AB  - The traditional view of nicotinic acetylcholine receptors (nAChRs) is that they
      strictly exert their functions via their well-known ion channel activity. With
      the identification of the cholinergic anti-inflammatory pathway and the critical
      involvement of the alpha7 nAChR, an alternate modality of function has emerged
      for the receptor involving metabotropic-like activity. The new emerging
      pharmacology for the receptor includes ligands termed silent agonists, which
      exert little or no ionotropic activity, yet are capable of modulating cellular
      inflammatory responses.

PMID- 29057038
TI  - Antibody-Drug Conjugates for the Treatment of Inflammation.

PMID- 29057039
TI  - Indolinone Inhibitors of ENT1 for the Treatment of Schizophrenia.

PMID- 29057040
TI  - Auranofin, Et3PAuCl, and Et3PAuI Are Highly Cytotoxic on Colorectal Cancer Cells:
      A Chemical and Biological Study.
AB  - The solution behavior of auranofin, Et3PAuCl  and Et3PAuI, as well as their
      interactions with hen egg white lysozyme, single strand oligonucleotide, and ds
      DNA were comparatively analyzed through NMR spectroscopy, ESI-MS, ethidium
      bromide displacement, DNA melting and viscometric tests. The cytotoxic effects
      toward representative colorectal cancer cell lines were found to be strong and
      similar in the three cases and a good correlation could be established between
      the cytotoxicity and the ability to inhibit thioredoxin reductase; remarkably, in
      vivo acute toxicity experiments for Et3PAuI confirmed that, similarly to
      auranofin, this drug is well tolerated in a murine model. Overall, a very similar
      profile emerges for Et3PAuI and Et3PAuCl, which retain the potent cytotoxic
      effects of auranofin while showing some peculiar features. These results
      demonstrate that the presence of the thiosugar moiety is not mandatory for the
      pharmacological action, suggesting that the tuning of some relevant chemical
      properties such as lipophilicity could be exploited to improve bioavailability,
      with no loss of the pharmacological effects.

PMID- 29057041
TI  - Discovery of a Tetrahydrobenzisoxazole Series of gamma-Secretase Modulators.
AB  - The design and synthesis of a new series of tetrahydrobenzisoxazoles as
      modulators of gamma-secretase activity and their structure-activity relationship
      (SAR) will be detailed. Several compounds are active gamma-secretase modulators
      (GSMs) with good to excellent selectivity for the reduction of Abeta42 in the
      cellular assay. Compound 14a was tested in vivo in a nontransgenic rat model and
      was found to significantly reduce Abeta42 in the CNS compartment compared to
      vehicle-treated animals (up to 58% reduction of cerebrospinal fluid Abeta42 as
      measured 3 h after an acute oral dosing at 30 mg/kg).

PMID- 29057042
TI  - Apratoxin S10, a Dual Inhibitor of Angiogenesis and Cancer Cell Growth To Treat
      Highly Vascularized Tumors.
AB  - Renal, hepatocellular, and neuroendocrine carcinomas are known as highly
      vascularized tumors. Although vascular endothelial growth factor A (VEGF-A)
      targeted therapies have shown efficacy in the treatment of these cancers, drug
      resistance is a major concern and might be mediated by interleukin 6 (IL-6).
      Furthermore, upon antiangiogenic drug exposure, tumor cells may adapt to survive
      in a vascular-independent manner. Apratoxins are potent marine-derived cytotoxic
      in vivo-active agents, preventing cotranslational translocation in the secretory
      pathway, and show promise to overcome resistance by targeting angiogenesis and
      tumor growth simultaneously. We designed and synthesized a novel apratoxin
      analogue, apratoxin S10, with a balanced potency and stability as well as
      synthetic accessibility and scalability. We showed that apratoxin S10 potently
      inhibits both angiogenesis in vitro and growth of cancer cells from vascularized
      tumors. Apratoxin S10 down-regulated vascular endothelial growth factor receptor
      2 (VEGFR2) on endothelial cells and blocked the secretion of VEGF-A and IL-6 from
      cancer cells. It inhibited cancer cell growth through down-regulation of multiple
      receptor tyrosine kinases (RTKs) and compares favorably to currently approved RTK
      inhibitors in both angiogenesis and cancer cell growth.

PMID- 29057043
TI  - Resorcinol-Based Grp94-Selective Inhibitors.
AB  - Glucose regulated protein 94 (Grp94) is the endoplasmic reticulum resident of the
      90 kDa heat shock protein (Hsp90) family and represents a promising therapeutic
      target for the treatment of several diseases. Grp94 is the most unique member of
      the 90 kDa heat shock protein family due to a five amino acid insertion into its
      primary sequence, which creates hydrophobic subpockets exclusive to Grp94 that
      can be utilized for selective inhibition. The first resorcinol-based Grp94
      selective inhibitor to take advantage of the hydrophobic S2 subpocket has been
      developed and shown to manifest low nanomolar affinity and ~10-fold selectivity
      for Grp94. Furthermore, these Grp94-selective inhibitors manifest low micromolar
      GI50 values against multiple myeloma cells, supporting Grp94 as an emerging
      target for the treatment of this disease.

PMID- 29057044
TI  - 6-Cyano Analogues of Bedaquiline as Less Lipophilic and Potentially Safer
      Diarylquinolines for Tuberculosis.
AB  - Bedaquiline (1) is a new drug for tuberculosis and the first of the
      diarylquinoline class. It demonstrates excellent efficacy against TB but induces
      phospholipidosis at high doses, has a long terminal elimination half-life (due to
      its high lipophilicity), and exhibits potent hERG channel inhibition, resulting
      in clinical QTc interval prolongation. A number of structural ring A analogues of
      bedaquiline have been prepared and evaluated for their anti-M.tb activity
      (MIC90), with a view to their possible application as less lipophilic second
      generation compounds. It was previously observed that a range of 6-substituted
      analogues of 1 demonstrated a positive correlation between potency (MIC90) toward
      M.tb and drug lipophilicity. Contrary to this trend, we discovered, by virtue of
      a clogP/M.tb score, that a 6-cyano (CN) substituent provides a substantial
      reduction in lipophilicity with only modest effects on MIC values, suggesting
      this substituent as a useful tool in the search for effective and safer analogues
      of 1.

PMID- 29057045
TI  - Artificial Macrocycles as Potent p53-MDM2 Inhibitors.
AB  - Based on a combination of an Ugi four component reaction and a ring closing
      metathesis, a library of novel artificial macrocyclic inhibitors of the p53-MDM2
      interaction was designed and synthesized. These macrocycles, alternatively to
      stapled peptides, target for the first time the large hydrophobic surface area
      formed by Tyr67, Gln72, His73, Val93, and Lys94 yielding derivatives with
      affinity to MDM2 in the nanomolar range. Their binding affinity with MDM2 was
      evaluated using fluorescence polarization (FP) assay and 1H-15N two-dimensional
      HSQC nuclear magnetic resonance experiments.

PMID- 29057046
TI  - Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6
      Inhibitors in Melanoma Models.
AB  - Only a handful of therapies offer significant improvement in the overall survival
      in cases of melanoma, a cancer whose incidence has continued to rise in the past
      30 years. In our effort to identify potent and isoform-selective histone
      deacetylase (HDAC) inhibitors as a therapeutic approach to melanoma, a series of
      new HDAC6 inhibitors based on the nexturastat A scaffold were prepared. The new
      analogues 4d, 4e, and 7b bearing added hydrophilic substituents, so as to
      establish additional hydrogen bonding on the rim of the HDAC6 catalytic pocket,
      exhibit improved potency against HDAC6 and retain selectivity over HDAC1.
      Compound 4d exhibits antiproliferative effects on several types of melanoma and
      lymphoma cells. Further studies indicates that 4d selectively increases
      acetylated tubulin levels in vitro and elicits an immune response through down
      regulating cytokine IL-10. A preliminary in vivo efficacy study indicates that 4d
      possesses improved capability to inhibit melanoma tumor growth and that this
      effect is based on the regulation of inflammatory and immune responses.

PMID- 29057047
TI  - Stabilizing a Tubulysin Antibody-Drug Conjugate To Enable Activity Against
      Multidrug-Resistant Tumors.
AB  - The tubulysins are promising anticancer cytotoxic agents due to the clinical
      validation of their mechanism of action (microtubule inhibition) and their
      particular activity against multidrug-resistant tumor cells. Yet their high
      potency and subsequent systemic toxicity make them prime candidates for targeted
      therapy, particularly in the form of antibody-drug conjugates (ADCs). Here we
      report a strategy to prepare stable and bioreversible conjugates of tubulysins to
      antibodies without loss of activity. A peptide trigger along with a quaternary
      ammonium salt linker connection to the tertiary amine of tubulysin provided ADCs
      that were potent in vitro. However, we observed metabolism of a critical acetate
      ester of the drug in vivo, resulting in diminished conjugate activity. We were
      able to circumvent this metabolic liability with the judicious choice of a propyl
      ether replacement. This modified tubulysin ADC was stable and effective against
      multidrug-resistant lymphoma cell lines and tumors.

PMID- 29057048
TI  - Targeting the Allosteric Site of Oncoprotein BCR-ABL as an Alternative Strategy
      for Effective Target Protein Degradation.
AB  - Protein degradation technology based on hybrid small molecules is an emerging
      drug modality that has significant potential in drug discovery and as a unique
      method of post-translational protein knockdown in the field of chemical biology.
      Here, we report the first example of a novel and potent protein degradation
      inducer that binds to an allosteric site of the oncogenic BCR-ABL protein. BCR
      ABL allosteric ligands were incorporated into the SNIPER (Specific and Nongenetic
      inhibitor of apoptosis protein [IAP]-dependent Protein Erasers) platform, and a
      series of in vitro biological assays of binding affinity, target protein
      modulation, signal transduction, and growth inhibition were carried out. One of
      the designed compounds, 6 (SNIPER(ABL)-062), showed desirable binding affinities
      against ABL1, cIAP1/2, and XIAP and consequently caused potent BCR-ABL
      degradation.

PMID- 29057049
TI  - Identification of Potent and Selective RIPK2 Inhibitors for the Treatment of
      Inflammatory Diseases.
AB  - NOD2 (nucleotide-binding oligomerization domain-containing protein 2) is an
      internal pattern recognition receptor that recognizes bacterial peptidoglycan and
      stimulates host immune responses. Dysfunction of NOD2 pathway has been associated
      with a number of autoinflammatory disorders. To date, direct inhibitors of NOD2
      have not been described due to technical challenges of targeting the oligomeric
      protein complex. Receptor interacting protein kinase 2 (RIPK2) is an
      intracellular serine/threonine/tyrosine kinase, a key signaling partner, and an
      obligate kinase for NOD2. As such, RIPK2 represents an attractive target to probe
      the pathological roles of NOD2 pathway. To search for selective RIPK2 inhibitors,
      we employed virtual library screening (VLS) and structure based design that
      eventually led to a potent and selective RIPK2 inhibitor 8 with excellent oral
      bioavailability, which was used to evaluate the effects of inhibition of RIPK2 in
      various in vitro assays and ex vivo and in vivo pharmacodynamic models.

PMID- 29057050
TI  - gem-Dinitroalkyl Benzenes: A Novel Class of IOP-Lowering Agents for the Treatment
      of Ocular Hypertension.
AB  - Primary open angle glaucoma is the second most common cause of blindness
      worldwide. Nitric oxide has recently received particular attention as a potential
      antiglaucoma agent. In this work, gem-dinitroalkyl benzenes are evaluated for
      their capability to act as a new class of IOP lowering agents. These derivatives
      have been endowed with a variety of NO-release capacities and found to relax
      contracted rat aorta strips in a concentration-dependent manner. They have been
      studied for their IOP-lowering activity in a transient ocular hypertensive rabbit
      model at 1% dose. The most effective IOP-lowering products were compounds 9-11
      and 13, whose activity was similar to that of Molsidomine 120 min after
      administration. Compounds 9 and 13 were selected for evaluation using carbomer
      induced glaucoma as the chronic model of IOP. They cause a significant reduction
      in IOP in the first 24 h, and their activity is maintained over 5 days,
      displaying a Molsidomine-like profile.

PMID- 29057051
TI  - Structure-Activity Relationship Study of Leucyl-3-epi-deoxynegamycin for Potent
      Premature Termination Codon Readthrough.
AB  - (+)-Negamycin, isolated from Streptomyces purpeofuscus, shows antimicrobial
      activity against Gram-negative bacteria and readthrough activity against nonsense
      mutations. Previously, we reported that two natural negamycin analogues, 5-deoxy
      3-epi-negamycin and its leucine adduct, have more potent readthrough activity in
      eukaryocytes (COS-7 cells) than negamycin but possess no antimicrobial activity
      and no in vitro readthrough activity in prokaryotic systems. In the present
      study, on leucyl-3-epi-deoxynegamycin, a structure-activity relationship study
      was performed to develop more potent readthrough agents. In a cell-based
      readthrough assay, the derivative 13b with an o-bromobenzyl ester functions as a
      prodrug and exhibits a higher readthrough activity against TGA-type PTC than the
      aminoglycoside G418. This ester (13b) shows an in vivo readthrough activity with
      low toxicity, suggesting that it has the potential for treatment of hereditary
      diseases caused by nonsense mutations.

PMID- 29057052
TI  - New Scaffold for Angiogenesis Inhibitors Discovered by Targeted Chemical
      Transformations of Wondonin Natural Products.
AB  - The structure of wondonin marine natural products was renovated to attain new
      drug-like scaffolds. Wondonins have novel antiangiogenic properties without overt
      cytotoxicity. However, the chemical instability and synthetic complexity of
      wondonins have hindered their development as a new type of antiangiogenesis
      agent. Using a structure-based bioisosterism, the benzodioxole moiety was changed
      to benzothiazole, and the imidazole moiety was replaced by 1,2,3-triazole. Our
      efforts resulted in a new scaffold with enhanced antiangiogenic activity and
      minimized cytotoxicity. One compound with this scaffold effectively inhibited
      hyaloid vessel formation in diabetic retinopathy mimic zebrafish model. The
      biological findings together suggested the potential of the scaffold as a lead
      structure for development of antiangiogenic drugs with novel functions and as a
      probe to elucidate new biological mechanisms associated with angiogenesis.

PMID- 29057053
TI  - Serotonin Analogues as Inhibitors of Breast Cancer Cell Growth.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is a critical local regulator of epithelial
      homeostasis in the breast and exerts its actions through a number of receptors.
      Dysregulation of serotonin signaling is reported to contribute to breast cancer
      pathophysiology by enhancing cell proliferation and promoting resistance to
      apoptosis. Preliminary analyses indicated that the potent 5-HT1B/1D serotonin
      receptor agonist 5-nonyloxytryptamine (5-NT), a triptan-like molecule, induced
      cell death in breast cancer cell lines. Thus, we synthesized a series of novel
      alkyloxytryptamine analogues, several of which decreased the viability of various
      human cancer cell lines. Proteomic and metabolomic analyses showed that compounds
      6 and 10 induced apoptosis and interfered with signaling pathways that regulate
      protein translation and survival, such as the Akt/mTOR pathway, in triple
      negative breast cancer cells.

PMID- 29057054
TI  - Discovery of Novel 5-(Piperazine-1-carbonyl)pyridin-2(1H)-one Derivatives as
      Orally eIF4A3-Selective Inhibitors.
AB  - Starting from our previous eIF4A3-selective inhibitor 1a, a novel series of
      (piperazine-1-carbonyl)pyridin-2(1H)-one derivatives was designed, synthesized,
      and evaluated for identification of orally bioavailable probe molecules.
      Compounds 1o and 1q showed improved physicochemical and ADMET profiles, while
      maintaining potent and subtype-selective eIF4A3 inhibitory potency. In accord
      with their promising PK profiles and results from initial in vivo PD studies,
      compounds 1o and 1q showed antitumor efficacy with T/C values of 54% and 29%,
      respectively, without severe body weight loss. Thus, our novel series of
      compounds represents promising probe molecules for the in vivo pharmacological
      study of selective eIF4A3 inhibition.

PMID- 29057055
TI  - Targeting Wall Teichoic Acid in Situ with Branched Polyethylenimine Potentiates
      beta-Lactam Efficacy against MRSA.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a medical concern. Here, we
      show that branched polyethylenimine (BPEI), a nontoxic, cationic polymer,
      restores MRSA's susceptibility to beta-lactam antibiotics. Checkerboard assays
      with MRSA demonstrated synergy between BPEI and beta-lactam antibiotics. A time
      killing curve showed BPEI to be bactericidal in combination with oxacillin. BPEI
      did not potentiate efficacy with vancomycin, chloramphenicol, or linezolid. When
      exposed to BPEI, MRSA increased in size and had difficulty forming septa. BPEI
      electrostatically binds to wall teichoic acid (WTA), a cell wall anionic polymer
      of Gram-positive bacteria that is important for localization of certain cell wall
      proteins. Lack of potentiation in a WTA knockout mutant supports the WTA-based
      mechanism. These data suggest that BPEI may prevent proper localization of cell
      wall machinery by binding to WTA; leading to cell death when administered in
      combination with beta-lactam antibiotics. Negligible in vitro toxicity suggests
      the combination could be a viable treatment option.

PMID- 29057056
TI  - 2-(4'-Aminophenyl)benzothiazole Labeled with 99mTc-Cyclopentadienyl for Imaging
      beta-Amyloid Plaques.
AB  - The development of a 99mTc-radiotracer for imaging of beta-amyloid (Abeta)
      plaques with single photon emission computed tomography (SPECT) is strongly
      anticipated to provide a low cost and broadly accessible diagnostic tool for
      Alzheimer's disease (AD). Within this framework, 2-(4'-aminophenyl)benzothiazole,
      known to display affinity and specificity for Abeta plaques, has been joined to
      the tricarbonyl fac-[M(CO)3]+ (M = Re(I), 99mTc(I)) core through the
      cyclopentadienyl moiety to yield stable, neutral, and lipophilic complexes (Re-1
      and 99mTc-1, respectively). The Re-1 complex was completely characterized with
      spectroscopic methods and was shown to selectively stain Abeta plaques on
      sections of human AD brain tissue. The 99mTc-1 complex displayed satisfactory
      initial brain uptake (0.53% ID/g at 2 min) and in vivo stability in healthy mice,
      while in transgenic 5xFAD mice, models for AD, a notable retention in the brain
      was noted (1.94% ID/g at 90 min). The results are encouraging and contribute to
      the effort of developing a SPECT amyloid imaging agent.

PMID- 29057057
TI  - From PIM1 to PI3Kdelta via GSK3beta: Target Hopping through the Kinome.
AB  - Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the
      treatment of inflammatory diseases. Initial optimization of a 3-substituted
      indazole hit compound targeting the kinase PIM1 focused on improving selectivity
      over GSK3beta through consideration of differences in the ATP binding pockets.
      Continued kinase cross-screening showed PI3Kdelta activity in a series of 4,6
      disubstituted indazole compounds, and subsequent structure-activity relationship
      exploration led to the discovery of an indole-containing lead compound as a
      potent PI3Kdelta inhibitor with selectivity over the other PI3K isoforms.

PMID- 29057058
TI  - Addressing the Metabolic Stability of Antituberculars through Machine Learning.
AB  - We present the first prospective application of our mouse liver microsomal (MLM)
      stability Bayesian model. CD117, an antitubercular thienopyrimidine tool compound
      that suffers from metabolic instability (MLM t1/2 < 1 min), was utilized to
      assess the predictive power of our new MLM stability model. The S-substituent was
      removed, a set of commercial reagents was utilized to construct a virtual library
      of 411 analogues, and our MLM stability model was applied to prioritize 13
      analogues for synthesis and biological profiling. In MLM stability assays, all 13
      analogues had superior metabolic stability to the parent compound, and six new
      analogues had acceptable MLM t1/2 values greater than or equal to 60 min. It is
      noteworthy that whole-cell efficacy and lack of relative mammalian cell
      cytotoxicity could not be predicted simultaneously. These results support the
      utility of our new MLM stability model in chemical tool and drug discovery
      optimization efforts.

PMID- 29057059
TI  - Lucky Switcheroo: Dramatic Potency and Selectivity Improvement of Imidazoline
      Inhibitors of Human Carbonic Anhydrase VII.
AB  - A substantial improvement of potency and selectivity of imidazoline-based
      inhibitors of hCA VII (a promising target for the treatment of seizures and
      neuropathic pain) was achieved by simply switching the position of the
      benzenesulfonamide moiety from N1 (as in the earlier reported series) to C2.
      Selectivity indices vs the off-target isoforms (hCA I, I, I and IV) greater than
      100 were reached, which is exceedingly rare for hCA VII inhibitors. The drastic
      profile improvement of the new series has been rationalized by an additional
      hydrogen bonding with the nonconserved Q69 residue in the active site of hCA VII
      (absent in the other three isoforms studied), which also results in a favorable
      accommodation of the inhibitor's lipophilic periphery in the nearby hydrophobic
      pocket. The robustness of the docking simulations was tested and confirmed by
      molecular dynamics simulations.

PMID- 29057060
TI  - Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a
      Series of Pyrazolo[1,5-a]pyrimidines.
AB  - Herein, we report the structure-activity relationships within a series of mGlu7
      PAMs based on a pyrazolo[1,5-a]pyrimidine core with excellent CNS penetration
      (Kps > 1 and Kp,uus > 1). Analogues in this series proved to display a range of
      Group III mGlu receptor selectivity, but VU6005649 emerged as the first dual
      mGlu7/8 PAM, filling a void in the Group III mGlu receptor PAM toolbox and
      demonstrating in vivo efficacy in a mouse contextual fear conditioning model.

PMID- 29057061
TI  - Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant
      IDH1 Inhibitor.
AB  - Inhibition of mutant IDH1 is being evaluated clinically as a promising treatment
      option for various cancers with hotspot mutation at Arg132. Having identified an
      allosteric, induced pocket of IDH1R132H, we have explored 3-pyrimidin-4-yl
      oxazolidin-2-ones as mutant IDH1 inhibitors for in vivo modulation of 2-HG
      production and potential brain penetration. We report here optimization efforts
      toward the identification of clinical candidate IDH305 (13), a potent and
      selective mutant IDH1 inhibitor that has demonstrated brain exposure in rodents.
      Preclinical characterization of this compound exhibited in vivo correlation of 2
      HG reduction and efficacy in a patient-derived IDH1 mutant xenograft tumor model.
      IDH305 (13) has progressed into human clinical trials for the treatment of
      cancers with IDH1 mutation.

PMID- 29057062
TI  - Discovery of Mechanism-Based Inactivators for Human Pancreatic Carboxypeptidase A
      from a Focused Synthetic Library.
AB  - Metallocarboxypeptidases (MCPs) are involved in many biological processes such as
      fibrinolysis or inflammation, development, Alzheimer's disease, and various types
      of cancer. We describe the synthesis and kinetic characterization of a focused
      library of 22 thiirane- and oxirane-based potential mechanism-based inhibitors,
      which led to discovery of an inhibitor for the human pro-carboxypeptidase A1. Our
      structural analyses show that the thiirane-based small-molecule inhibitor
      penetrates the barrier of the pro-domain to bind within the active site. This
      binding leads to a chemical reaction that covalently modifies the catalytic
      Glu270. These results highlight the importance of combined structural,
      biophysical, and biochemical evaluation of inhibitors in design strategies for
      the development of spectroscopically nonsilent probes as effective beacons for in
      vitro, in cellulo, and/or in vivo localization in clinical and industrial
      applications.

PMID- 29057063
TI  - Is surgical debridement necessary in the diabetic foot treated with photodynamic
      therapy?
AB  - Background: Diabetic patients are susceptible to developing foot ulcers with
      serious complications such as osteomyelitis and amputations. Treatment approaches
      are still empirical and the benefit of usual procedures such as surgical
      debridement has not been properly evaluated. Photodynamic Therapy (PDT) is a non
      invasive and highly efficient method for the treatment of the diabetic foot,
      being able to eradicate the infection and to stimulate healing, decreasing
      considerably the amputation risk. In the day-to-day practice of our service, we
      have been faced with the question whether debridement is necessary before PDT. In
      here, we designed a study to answer that question. Methods: Patients were divided
      in two groups: In one of the groups (n = 17), debridement was performed before
      PDT and in the other (n = 40) only PDT treatment was performed. PDT sessions were
      performed once a week in all patients until healing was achieved, as indicated by
      visual inspection as well as by radiographic and laboratory exams. At the start
      of the study, the two groups had no statistical differences concerning their
      clinical features: average age, gender, insulin use, diabetes mellitus onset time
      and previous amputations. Results: PDT was effective in the treatment of 100% of
      the patients showing no relapses after one year of follow up. The group submitted
      to PDT without previous debridement had a statistically significant (p = 0.036,
      Mann-Whitney) shorter cure time (29 days, ~27%). Conclusion: Our data indicates
      that debridement is not necessary in the treatment of diabetic foot in patients
      that have enough peripheral arterial perfusion. In addition, we reproduced
      previous studies confirming that PDT is an efficient, safe, simple and affordable
      treatment method for the diabetic foot.

PMID- 29057064
TI  - Beyond dichotomous thinking: a process perspective on diabetic foot disease.
AB  - Background: Diabetic foot (DF) disease causes severe suffering around the world,
      and appropriate self-care activities are needed to prevent and treat this
      condition. However, all too often, self-care activities are less than optimal and
      clinicians find themselves unable to influence them in a positive direction.
      Clinicians' and researchers' mental models of the DF tend to be dichotomous:
      either the patient has or does not have an active ulcer or other DF disease. This
      mode of thinking hides the long-term perspective of DF disease, where patients'
      previous experiences and expectations for the future influence their current
      behavior. Thus, there is a need for a different perspective on DF disease to
      better understand patients' perspectives and thereby improve self-care, leading
      to more effective prevention and treatment. Objective: To present a novel
      framework, the process perspective on the DF, which can explain inadequate self
      care behaviors not easily understood with a dichotomous perspective, and how they
      can be changed. Results: Three fictive clinical examples are used to illustrate
      how the process perspective on the DF can be used to understand how patients'
      previous experiences and expectations for the future influence their current
      behavior. In particular, this process perspective is used to understand how
      patients' beliefs and behaviors are sometimes self-reinforcing, resulting in
      stable behavior patterns, here referred to as 'DF cycles'. These cycles are quite
      common in clinical practice but are difficult to analyze using a dichotomous
      perspective on DF disease. The process perspective on the DF is used to analyze
      specific 'vicious' DF cycles of inadequate patient behavior and to find ways to
      transform them into 'virtuous' DF cycles, resulting in effective prevention and
      treatment. Conclusions: The process perspective on the DF seems suitable for
      understanding inadequate patient behaviors not easily understood with a
      dichotomous perspective on DF disease, opening up new avenues for clinical
      practice and research to help patients live a life with long remission phases,
      few relapses, and a high quality of life.

PMID- 29057065
TI  - Targeting the small airways with dry powder adenosine: a challenging concept.
AB  - Background: Small-particle inhaled corticosteroids (ICS) provide a higher small
      airway deposition than large-particle ICS. However, we are still not able to
      identify asthma patients who will profit most from small-particle treatment.
      Objective: We aimed to identify these patients by selectively challenging the
      small and large airways. We hypothesized that the airways could be challenged
      selectively using small- and large-particle adenosine, both inhaled at a high and
      a low flow rate. Design: In this cross-over study 11 asthma subjects performed
      four dry powder adenosine tests, with either small (MMAD 2.7 um) or large (MMAD
      6.0 um) particles, inhaled once with a low flow rate (30 l min-1) and once with a
      high flow rate (60 l min-1). Spirometry and impulse oscillometry were performed
      after every bronchoprovocation step. We assumed that FEV1 reflects the large
      airways, and FEF25-75%, R5-R20 and X5 reflect the small airways. Results: The
      four adenosine tests were not significantly different with respect to the
      threshold values of FEV1 (p = 0.12), FEF25-75% (p = 0.37), R5-R20 (p = 0.60) or
      X5 (p = 0.46). Both small- and large-particle adenosine induced a response in the
      small airways in the majority of the tests. Conclusions: In contrast to our
      hypothesis, all four adenosine tests provoked a response in the small airways and
      we could not identify different large- or small-airway responders. Interestingly,
      even the test with large particles and a high flow rate induced a small-airway
      response, suggesting that selective challenging of the small airways is not
      necessary. Future studies should investigate the relation between particle
      deposition and the site of an airway response.

PMID- 29057066
TI  - Taste in Art-Exposure to Histological Stains Shapes Abstract Art Preferences.
AB  - Exposure to art increases the appreciation of artworks. Here, we showed that this
      effect is domain independent. After viewing images of histological stains in a
      lecture, ratings increased for restricted subsets of abstract art images. In
      contrast, a lecture on art history generally enhanced ratings for all art images
      presented, while a lecture on town history without any visual stimuli did not
      increase the ratings. Therefore, we found a domain-independent exposure effect of
      images of histological stains to particular abstract paintings. This finding
      suggests that the 'taste' for abstract art is altered by visual impressions that
      are presented outside of an artistic context.

PMID- 29057067
TI  - Identification of a unique gene expression signature in mercury and 2,3,7,8
      tetrachlorodibenzo-p-dioxin co-exposed cells.
AB  - Mercury (Hg) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are major
      environmental contaminants that commonly co-occur in the environment. Both Hg and
      TCDD are associated with a number of human diseases including cancers. While the
      individual toxicological effects of Hg and TCDD have been extensively
      investigated, studies on co-exposure are limited to a few genes and pathways.
      Therefore, a significant knowledge gap exists in the understanding of the
      deleterious effects of co-exposure to Hg and TCDD. Due to the prevalence of Hg
      and TCDD co-contamination in the environment and the major human health hazards
      they pose, it is important to obtain a fuller understanding of genome-wide
      effects of Hg and TCDD co-exposure. In this study, by performing a comprehensive
      transcriptomic analysis of human bronchial epithelial cells (BEAS-2B) exposed to
      Hg and TCDD individually and in combination, we have uncovered a subset of genes
      with altered expression only in the co-exposed cells. We also identified the
      additive as well as antagonistic effects of Hg and TCDD on gene expression.
      Moreover, we found that co-exposure impacted several biological and disease
      processes not affected by Hg or TCDD individually. Our studies show that the
      consequences of Hg and TCDD co-exposure on the transcriptional program and
      biological processes could be substantially different from single exposures, thus
      providing new insights into the co-exposure-specific pathogenic processes.

PMID- 29057068
TI  - Case report: Percutaneous electrical neural field stimulation in two cases of
      sympathetically-mediated pain.
AB  - Background: Fibromyalgia and complex regional pain syndrome (CRPS) are both
      chronic pain syndromes with pathophysiologic mechanisms related to autonomic
      nervous system dysregulation and central sensitization.  Both syndromes are
      considered difficult to treat with conventional pain therapies. Case
      presentations: Here we describe a female veteran with fibromyalgia and a male
      veteran with CRPS, both of whom failed multiple pharmacologic, physical and
      psychological therapies for pain, but responded to percutaneous electrical neural
      field stimulation (PENFS) targeted at the auricular branches of the cranial
      nerves. Discussion: While PENFS applied to the body has been previously described
      for treatment of localized pain, PENFS effects on cranial nerve branches of the
      ear is not well-known, particularly when used for regional and full-body pain
      syndromes such as those described here. PENFS of the ear is a minimally-invasive,
      non-pharmacologic therapy that could lead to improved quality of life and
      decreased reliance on medication. However, further research is needed to guide
      clinical application, particularly in complex pain patients.

PMID- 29057069
TI  - Giving eyespots a shiner: Pharmacologic manipulation of the Io moth wing pattern.
AB  - Our knowledge of wing pattern formation in Lepidoptera has advanced significantly
      in recent years due to the careful examination of several groups of butterflies.
      The eyespot is a prominent feature of Lepidoptera wing pattern, especially in the
      family Saturniidae. The present study examined how sulfated polysaccharides,
      which are known to simulate cold shock effect in nymphalid butterflies, affected
      the wing pattern formation of the Io moth, Automeris io (Saturniidae).  Prepupae
      and pupae of this species were subjected to injections of heparin and cold shock.
      While the cold shock had little to no effect on wing pattern, the aberrations
      resulting from heparin injections consisted of moderate to profound increases in
      melanism around the eyespots. The resulting aberrations are dubbed 'Black Eye'
      and 'Comet Eye.' Most other known aberrations of Automeris io eyespots are
      summarized, illustrated and named.

PMID- 29057071
TI  - Solid phase synthesis and RNA-binding activity of an arginine-containing
      nucleopeptide.
AB  - Here we report the solid phase synthesis and characterization (LC-ESIMS, CD) of a
      cationic nucleobase-containing alpha-peptide, composed of both l-arginine
      residues and l-lysine-based nucleoamino acids sequentially present in the
      structure. The binding properties of this novel basic nucleopeptide towards
      nucleic acids were investigated by CD spectroscopy which revealed the ability of
      the thymine-containing oligomer to bind both adenine-containing DNA (dA12) and
      RNA (poly rA) molecules inducing high conformational variations in the nucleic
      acid structures. Moreover, the artificial oligonucleotide inhibited the enzymatic
      activity of HIV reverse transcriptase, opening the door to the exploitation of
      novel antiviral strategies inspired to this molecular tool.

PMID- 29057070
TI  - Tourette syndrome research highlights from 2016.
AB  - This article presents highlights chosen from research that appeared during 2016
      on Tourette syndrome and other tic disorders. Selected articles felt to represent
      meaningful advances in the field are briefly summarized.

PMID- 29057072
TI  - Solid phase synthesis of TyrT, a thymine-tyrosine conjugate with poly(A) RNA
      binding ability.
AB  - The present work deals with the synthesis and characterization of a novel
      nucleoamino acid derivative based on a l-tyrosine moiety to which a thymine
      nucleobase was anchored by means of an amide bond to the N-alpha group. This
      derivative, denominated by us TyrT, belongs to the family of the nucleobase-amino
      acid conjugates that show a wide range of biological activities, frequently
      associated with their ability to interact with nucleic acids. In this respect,
      the interaction of TyrT with poly(A), a proposed RNA target for anticancer
      strategies, was studied by circular dichroism (CD) which suggested its ability to
      bind this RNA. Moreover, the modification of the morphology of a sample of TyrT
      in the presence of poly(A) was visualised by scanning electron microscopy (SEM)
      which was in agreement with the evidence that the thyminyl l-tyrosine interacts
      with poly(A). Finally, computational analyses have been performed to hypothesize
      the binding mode from a structural point of view, suggesting that the binding is
      mainly kept via hydrophobic contacts, reproducing a stacking-like interaction
      between the thymine ring of TyrT and the two successive adenine rings of a
      poly(A) model.

PMID- 29057073
TI  - Effect of physician characteristics and knowledge on the quality of dyslipidemia
      management and LDL-C target goal achievement in China: Subgroup analysis of the
      Dyslipidemia International Study.
AB  - OBJECTIVE: This study aimed to investigate the effect of physicians'
      characteristics and knowledge of LDL-C target goals on the quality of lipid
      management in China. METHODS: A total of 25 317 dyslipidemia patients who had
      taken lipid-lowering medication for >3 months were enrolled in our study.
      Patients' demographic data, medical history, lipid profile, their physician's
      specialty and professional title and their hospital level as well as their LDL-C
      goal opinions were recorded. RESULTS: Questionnaires were completed by 926
      physicians with 6 different specialties and 4 professional statuses, in 3
      different-level hospitals. Most (74.5%) of the physicians recognized the
      importance of considering LDL-C serum concentration for treating dyslipidemia,
      and set target LDL-C goals according to the 2007 Chinese guidelines for 83.4% of
      their patients. The LDL-C goal achievement rate was significantly higher for
      patients whose physicians' knowledge of LDL-C target goals was consistent with
      guideline recommendations, compared with those whose physicians' knowledge was
      inconsistent with the guidelines (60.4% vs 31.1%, P < 0.0001). Physicians working
      in tier 1 (odds ration (OR) = 2.95; 95% CI 2.37-3.67), (OR = 1.56; 95% CI 1.34
      1.81) and tier 2 (OR = 2.53; 95% CI 2.22-2.88), (OR = 1.16; 95% CI 1.06-1.27)
      hospitals, specialized in neurology (OR = 1.13; 95% CI 0.93-1.36), (OR = 1.57;
      95% CI 1.40-1.77), internal medicine (OR = 1.07; 95% CI 0.90-1.27), (OR = 1.58;
      95% CI 1.39-1.80), endocrinology (OR = 1.02; 95% CI 0.87-1.21), (OR = 1.63; 95%
      CI 1.47-1.82) and being a resident vs attending physician (OR = 1.05; 95% CI 0.92
      1.20), (OR = 1.00; 95% CI 1.00-1.19) were independent risk factors for low
      knowledge of LDL-C target goals and low LDL-C goal achievement. CONCLUSION:
      Chinese physicians' characteristics and knowledge of LDL-C target goals were
      associated with patients' LDL-C goal achievement.

PMID- 29057075
TI  - Biosilver nanoparticle interface offers improved cell viability.
AB  - Silver nanoparticles (AgNP) are promising candidates for fighting drug-resistant
      infections because of their intrinsic antimicrobial effect. The design of high
      yield antimicrobial molecules may inadvertently cause variation in host cells'
      biological responses. While many factors affect AgNPs' efficacy, their surface is
      exposed to the biological environment and thus plays a critical role in both the
      preservation of antimicrobial efficacy against pathogens and the modulation of
      host cells cytotoxicity. This work investigated an engineered biomimetic
      interface approach to controlling AgNP surface properties to provide them a
      competitive advantage in a biological environment. Here, a fusion protein
      featuring a silver-binding peptide (AgBP) domain was engineered to enable self
      assembly and track assembly by a green fluorescent protein (GFP) reporter.
      Following AgNP functionalisation with GFP-AgBP, their antimicrobial and cytotoxic
      properties were evaluated. GFP-AgBP binding affinity to AgNPs was evaluated using
      localized surface plasmon resonance sensing. The GFP-AgBP biomimetic interface on
      AgNPs' surfaces provided sustained antibacterial efficacy at low concentrations
      based on bacterial growth inhibition assays. Viability and cytotoxicity
      measurements in fibroblast cells exposed to GFP-AgBP protein-functionalised AgNPs
      showed significant improvement compared to controls. Biointerface engineering
      offers promise towards tailoring AgNP antimicrobial efficacy while addressing
      safety concerns to maintain optimum cellular interactions.

PMID- 29057074
TI  - Consensus-based approach to develop a measurement framework and identify a core
      set of indicators to track implementation and progress towards effective coverage
      of facility-based Kangaroo Mother Care.
AB  - BACKGROUND: As efforts to scale up the delivery of Kangaroo Mother Care (KMC) in
      facilities are increasing, a standardized approach to measure implementation and
      progress towards effective coverage is needed. Here, we describe a consensus
      based approach to develop a measurement framework and identify a core set of
      indicators for monitoring facility-based KMC that would be feasible to measure
      within existing systems. METHODS: The KMC measurement framework and core list of
      indicators were developed through: 1) scoping exercise to identify potential
      indicators through literature review and requests from researchers and program
      implementers; and 2) face-to-face consultations with KMC and measurement experts
      working at country and global levels to review candidate indicators and finalize
      selection and definitions. RESULTS: The KMC measurement framework includes two
      main components: 1) service readiness, based on the WHO building blocks
      framework; and 2) service delivery action sequence covering identification,
      service initiation, continuation to discharge, and follow-up to graduation.
      Consensus was reached on 10 core indicators for KMC, which were organized
      according to the measurement framework. We identified 4 service readiness
      indicators, capturing national level policy for KMC, availability of KMC
      indicators in HMIS, costed operational plans for KMC and availability of KMC
      services at health facilities with inpatient maternity services. Six indicators
      were defined for service delivery, including weighing of babies at birth,
      identification of those <=2000 g, initiation of facility-based KMC, monitoring
      the quality of KMC, status of babies at discharge from the facility and levels of
      follow-up (according to country-specific protocol). CONCLUSIONS: These core KMC
      indicators, identified with input from a wide range of global and country-level
      KMC and measurement experts, can aid efforts to strengthen monitoring systems and
      facilitate global tracking of KMC implementation. As data collection systems
      advance, we encourage program managers and evaluators to document their
      experiences using this framework to measure progress and allow indicator
      refinement, with the overall aim of working towards sustainable, country-led data
      systems.

PMID- 29057077
TI  - The Impact of Aggregation on the p-Doping Kinetics of Poly(3-hexylthiophene).
AB  - The morphological effects of regioregular poly(3-hexylthiophene) (P3HT) on its p
      doping kinetics with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4
      TCNQ) in solution are studied using optical absorption spectroscopy and stopped
      flow technique. Two morphological forms, solubilized (s-P3HT) and nanowhiskers
      (nw-P3HT), are investigated. Both P3HT solubilized and aggregated solutions show
      similar characteristic near-IR absorption bands for integer charge transfer
      products with F4-TCNQ. Kinetic analysis on p-doping of s-P3HT with F4-TCNQ
      indicates that the doping reaction proceeds with a single reaction mechanism that
      is first order in s-P3HT. The doping kinetics of P3HT aggregate solution shows
      two distinctive reaction mechanisms. The slow mechanism has a reaction rate
      constant similar to that of solubilized P3HT solution, so it likely results from
      s-P3HT components that are present in the aggregate solution. The fast one is
      assigned to the nw-P3HT component, probably due to more efficient charge
      delocalization in the aggregated P3HT nanostructures. Additionally, the kinetic
      trends of the p-doping reactions are better fitted with the consideration of a
      Gaussian-like distribution of reactivities from P3HT, matching the complexity of
      polymeric systems originating from molecular weight and morphology variations.
      This study highlights the importance of considering different morphological forms
      of conjugated polymers on their charge-transfer reaction kinetics. The knowledge
      gained here should be fundamentally and practically important for future chemical
      doping applications in organic electronic device fabrications.

PMID- 29057076
TI  - Three-dimensional fabrication of cell-laden biodegradable poly(ethylene glycol-co
      depsipeptide) hydrogels by visible light stereolithography.
AB  - Stereolithography (SLA) holds great promise in fabrication of cell-laden
      hydrogels with biomimetic complexity for use in tissue engineering and
      pharmaceutics. However, the availability of biodegradable photocrosslinkable
      hydrogel polymers for SLA is very limited. In this study, a water-soluble
      methacrylated poly(ethylene glycol-co-depsipeptide) was synthesized to yield a
      biodegradable photocrosslinkable macromer for SLA. Structural analysis confirmed
      the inclusion of biodegradable peptide and ester groups and photocrosslinkable
      methacrylate groups into the polymer backbone. The new macromer combined with
      RGDS peptide was used for SLA fabrication of hydrogels in absence and presence of
      cells. With the increasing light exposure time in SLA, mechanical stiffness of
      the hydrogels increased from 3 +/- 1 kPa to 38 +/- 13 kPa. Total mass loss of the
      samples within 7 days in PBS was 13%-21% and within 24 days 35%-66%. Due to
      degradation, the mechanical stiffness decreased by one order magnitude within 7
      day incubation in PBS. Encapsulated endothelial cells proliferated in the
      hydrogels during 10-day in vitro cell culturing study. The macromer was further
      used in SLA to fabricate bifurcating tubular structures as preliminary vessel
      grafts. The new biodegradable, photocrosslinkable polymer is a significant
      addition to the very limited material selection currently available for SLA-based
      fabrication of cell-laden tissue engineering constructs.

PMID- 29057078
TI  - Materials and toxicological approaches to study metal and metal-oxide
      nanoparticles in the model organism Caenorhabditis elegans.
AB  - Understanding the in vivo fate and transport of nanoparticles (NPs) is
      challenging, but critical. We review recent studies of metal and metal oxide NPs
      using the model organism Caenorhabditis elegans, summarizing major findings to
      date. In a joint transdisciplinary effort, we highlight underutilized
      opportunities offered by powerful techniques lying at the intersection of
      mechanistic toxicology and materials science,. To this end, we firstly summarize
      the influence of exposure conditions (media, duration, C. elegans lifestage) and
      NP physicochemical properties (size, coating, composition) on the response of C.
      elegans to NP treatment. Next, we focus on the techniques employed to study NP
      entrance route, uptake, biodistribution and fate, emphasizing the potential of
      extending the toolkit available with novel and powerful techniques. Next, we
      review findings on several NP-induced biological responses, namely transport
      routes and altered molecular pathways, and illustrate the molecular biology and
      genetic strategies applied, critically reviewing their strengths and weaknesses.
      Finally, we advocate the incorporation of a set of minimal materials and
      toxicological science experiments that will permit meta-analysis and synthesis of
      multiple studies in the future. We believe this review will facilitate
      coordinated integration of both well-established and underutilized approaches in
      mechanistic toxicology and materials science by the nanomaterials research
      community.

PMID- 29057079
TI  - Size Effect of the Active Sites in UiO-66-Supported Nickel Catalysts Synthesized
      via Atomic Layer Deposition for Ethylene Hydrogenation.
AB  - Ni(II) ions have been deposited on the Zr6 nodes of a metal-organic framework
      (MOF), UiO-66, via an ALD-like process (ALD = atomic layer deposition). By
      varying the number of ALD cycles, three Ni-decorated UiO-66 materials were
      synthesized. A suite of physical methods has been used to characterize these
      materials, indicating structural and high-surface-area features of the parent MOF
      are retained. Elemental analysis via X-ray photoelectron spectroscopy (XPS)
      indicates that the anchored Ni ions are mainly on surface and near-surface MOF
      defect sites. Upon activation, all three materials are catalytic for ethylene
      hydrogenation, but their catalytic activities significantly vary, with the
      largest clusters displaying the highest per-nickel-atom activity. The study
      highlights the ease and effectiveness ALD in MOFs (AIM) for synthesizing,
      specifically, UiO-66-supported NiyOx catalysts.

PMID- 29057080
TI  - The role of miR-29a in HIV-1 replication and latency.
AB  - The development of an effective HIV-1 eradication strategy relies upon a clear
      understanding of the cellular mechanisms involved in HIV-1 latency. Among such
      cellular processes, microRNA activities affect HIV-1 production by regulating
      viral transcripts as well as host cell HIV-1 dependency factors. miR-29a stands
      apart from other relevant microRNAs as a potential therapeutic target in HIV-1
      eradication. In vitro experiments have shown that miR-29a binds to a sequence in
      the 3'UTR of viral transcripts and inhibits their expression. In vivo data
      revealed the existence of a cytokine-microRNA (i.e. IL-21/miR-29a) pathway that
      significantly impacts HIV-1 replication. Here we present and discuss evidence
      supporting the role of miR-29a in HIV-1 replication and latency. We also discuss
      potential clinical applications of miR-29a inhibitors and enhancers in HIV-1
      eradication strategies.

PMID- 29057081
TI  - The challenges of ending AIDS in Asia: outcomes of the Thai National AIDS
      Universal Coverage Programme, 2000-2014.
AB  - OBJECTIVES: We sought to determine Thai National AIDS Program (NAP) outcomes and
      gaps, and success in reaching the WHO 90:90:90 goals. METHODS: Retrospective
      study of treatment outcomes, mortality and loss to follow-up (LTFU), of all
      individuals aged >15 years who registered to the NAP from 2000 to 2014. We
      focused outcomes on data from 2008 when the NAP was linked to the death registry.
      RESULTS: A total of 429,294 patients registered to the NAP up to November 2014,
      and 309,313 patients aged >15 years started ART. Median (IQR) age was 37 (31-43)
      years; 51% were male. From 2008 to 2014, long-term follow-up rates per 100 person
      years were 3.2 in those who started ART vs 3.5 in those who did not (P<0.001) and
      mortality rates per 100 person-years were 3.5 in those who started ART vs 4.9 in
      those who did not (P<0.001). Mortality reduced from 16% in 2008 to 3% in 2014 for
      those who started ART. For patients starting treatment since 2000, 87% of those
      alive and with a recent viral load (VL) result had <50 copies/mL, and 6% had VL
      >=1000 copies/mL. In a continuum-of-care analysis from 2008 to 2014, 68% were
      living and retained on ART, and 46% of diagnosed individuals were virally
      suppressed at <50 copies/mL. CONCLUSIONS: In the Thai NAP, death and LTFU are
      major factors disrupting the care-continuum, and many patients initiate ART with
      low CD4 cell counts. Rolling out systems for early detection and treatment for
      all, regardless of CD4 cell count, are essential and under way.

PMID- 29057082
TI  - High sustained virological response rates using imported generic direct acting
      antiviral treatment for hepatitis C.
AB  - BACKGROUND: High prices of direct acting antivirals (DAAs) for hepatitis C virus
      (HCV) can lead to restrictions on access to treatment in high- and middle-income
      countries. An increasing number of people in these countries are treating their
      HCV infection with generic drugs produced in India, China, Bangladesh or Egypt.
      This analysis assessed the efficacy of generic imported DAAs. METHODS: Patients
      sourced generic versions of sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir
      (DCV) from suppliers in India, Bangladesh, China and Egypt via three buyers'
      clubs. The choice of DAAs and the length of treatment were determined on baseline
      RNA levels, HCV genotype and stage of fibrosis. Patient HCV RNA levels were
      evaluated pre-treatment, during treatment, at end of treatment (EOT) and then for
      sustained virological response (SVR) at 4, 12, and 24 weeks, normally by a
      treating clinician. RESULTS: Overall 616 patients submitted results: 199 from an
      Australian buyers' club, 205 from a South-east Asian buyers' clubs, and 212 from
      an Eastern European buyers' club. Of the 616 patients treated, 276 received
      SOF/LDV (35 with ribavirin [RBV]) and 340 received SOF/DCV (61 with RBV). At
      baseline, 61% were male, 52% had HCV genotype 1 and 11% had liver cirrhosis. The
      mean age was 44.3 years and the mean baseline HCV RNA was 6.9 log10 IU/mL. A
      rapid virological response (RVR) was observed in 314/375 (84%) of the patients
      treated. Based on currently available data, the percentage of patients with HCV
      RNA below the lower limit of quantification (LLoQ) was 99% (234/237) at EOT, 99%
      (299/303) at SVR4 and 99% (247/250) at SVR12. CONCLUSIONS: In this analysis,
      treatment with imported generic DAAs achieved high rates of HCV RNA
      undetectability at the end of treatment, and SVR12 in 99% of patients evaluated
      to date. Mass treatment with generic DAAs is a feasible and economical
      alternative route of accessing curative DAAs, where the high prices for branded
      alternatives prevent access to treatment.

PMID- 29057083
TI  - Low-level genital HIV shedding in Thai HIV-infected women with suppressed plasma
      viral load after menopause: a longitudinal study.
AB  - OBJECTIVES: First, to evaluate the longitudinal changes of HIV RNA in genital
      secretions in HIV-positive women with plasma HIV RNA <50 copies/mL before and
      after the onset of menopause. Second, to assess inflammatory markers and
      prevalence of comorbidities after the onset of menopause. METHODS: This was a
      prospective observational study with two time points. HIV RNA in genital
      secretions (GVL) was measured in 15 HIV-positive menopausal women (second time
      point). Results were compared to earlier available data for GVL from the same
      participant before the onset of menopause (first time point). RESULTS: Median age
      at the first time point was 42 years, and 52 years at the second time point.
      Median time since the onset of menopause was 2 years and 33% of women were
      sexually active. Eighty per cent had at least one comorbidity. The GVL before
      menopause was >50 copies/mL in 27% of the participants, and in 40% after
      menopause. The GVL was <1000 copies/mL in all but one measurement. There was no
      significant difference between the two time points (P=0.687). Intermediate
      vaginal flora or bacterial vaginosis was found in 73% of participants during the
      second time point. CONCLUSIONS: There was a high prevalence of low-level GVL
      shedding before and after menopause. This needs further investigation, especially
      in relation to the vaginal microbiome and the complex interactions between micro
      organisms. HIV-infected women in menopause do not seem to present a major public
      health risk for HIV transmission. Nevertheless, safe sex should be discussed with
      all, regardless of age. The high prevalence of non-communicable diseases after
      menopause requires special attention and comprehensive care.

PMID- 29057084
TI  - Changes in the haematological parameters of HIV-1 infected children at 6 and 12
      months of antiretroviral therapy in a large clinic cohort, North-Central Nigeria.
AB  - BACKGROUND: Prior to commencing antiretroviral therapy (ART), haematological
      abnormalities are a common occurrence in individuals diagnosed with human
      immunodeficiency virus (HIV). In the course of receiving ART, these abnormalities
      usually improve. We determined the prevalence of haematological abnormalities in
      children diagnosed with HIV-1 and the changes in haematological parameters that
      occur after 6 and 12 months of being on ART. METHODS: A cross-sectional study of
      HIV-1 infected children aged 2 months to 15 years, between July 2005 and March
      2013, at the paediatric HIV clinic of the Jos University Teaching Hospital, Jos.
      Median values of repeated measures were compared using the Wilcoxon signed-rank
      sum test. RESULTS: The prevalence of anaemia, thrombocytopenia and leukopenia
      among the 941 children studied, prior to ART was 6.4%, 7.0% and 8.6%. Median
      (IQR) haemoglobin (Hb) levels increased from 10 g/dL (9-11 g/dL) at baseline to
      11 g/dL (10-12 g/dL) and 11 g/dL (10-12 g/dL) at 6 and 12 months of ART (P<0.001
      and P<0.001), respectively, a 10% increase in both cases. Also, platelet count
      increased from a median of 327*103/MUL (243-426*103/MUL) at baseline to
      333*103/MUL (266-408*103/MUL) at 6 months and 339*103/MUL (267-420*103/MUL) at 12
      months, representing a 1.8% and 3.7% increase, respectively. The median total
      white blood cell count decreased from 7.4*103/MUL (5.3-9.9*103/MUL) at baseline
      to 5.9*103/MUL (4.6-8.0*103/MUL) and 5.8*103/MUL (4.5-7.5*103/MUL) at 6 and 12
      months of ART (P<0.001 and P<0.001), a 20.3% and 21.6% decrease, respectively.
      CONCLUSION: During the 12 months of ART, children in our cohort had significant
      improvements in haematological parameters such as haemoglobin levels and platelet
      counts, which would suggest an early positive response to ART.

PMID- 29057085
TI  - The evaluation of risk-benefit ratio for gut tissue sampling in HIV cure
      research.
AB  - INTRODUCTION: Antiretroviral therapy (ART) does not cure HIV infection due to the
      persistence of HIV reservoirs in long-lived memory CD4 T cells present in the
      blood, lymph nodes, intestinal tract, and other tissues. Interest grows in
      obtaining gut-tissue samples for HIV persistence studies, which poses an ethical
      challenge to provide study volunteers with adequate information on risks and
      benefits. Herein we assess the risks and benefits of undergoing gut biopsy
      procedures for HIV pathogenesis and reservoir studies. METHODS: A group
      discussion was organised with physicians and community representatives on
      performing either a flexible sigmoidoscopy or a colonoscopy. Consensus was
      reached on conducting colonoscopy in persons >=50 years. Thirty HIV-infected, ART
      treated and nine uninfected participants were recruited. Colonoscopy was
      performed to collect 30 gut mucosal biopsies. When present, polyps were removed
      and abnormal mucosal findings were biopsied for pathological analysis.
      Participants were interviewed on potential discomfort following colonoscopic
      examination. RESULTS: The HIV-infected and uninfected groups were comparable in
      terms of age and gender with more men who have sex with men (MSM) in the former
      group. Abnormal colonoscopic findings were observed in 43.6% of all the
      participants and did not differ by HIV status. In total, 24 polyps were removed
      with a higher mean number of polyps removed in HIV-infected versus uninfected
      participants (1.7 vs 1.0, P=0.013). The number of polyps marginally correlated
      with inverted CD4:CD8 ratio. Based on our findings, colonoscopic examination was
      safe to use for gut biopsy procedures where almost half of the participants had
      polyps removed. CONCLUSION: Participation in the study provided colon cancer
      screening as an ancillary benefit that participants could have received in
      standard medical care, thus mitigating burdens of invasive procedures. Dialogue
      between community representatives and clinical researchers can increase
      participation and advance HIV cure research.

PMID- 29057086
TI  - InterPrEP. Internet-based pre-exposure prophylaxis with generic tenofovir
      DF/emtricitabine in London: an analysis of outcomes in 641 patients.
AB  - INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) is not available on the
      National Health Service (NHS) in England. People are buying generic versions of
      tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) on the internet, which is
      legal under UK import laws. METHODS: HIV-negative individuals attending our
      clinic who reported purchasing generic PrEP online were provided with risk
      reduction advice and were evaluated for HIV, hepatitis B and C, renal function
      and sexually transmitted infections (STIs)on their first visit. They were offered
      regular follow-up visits every 3 months and given risk-reduction advice. Plasma
      therapeutic drug monitoring (TDM) for tenofovir and FTC was also offered.
      RESULTS: 641 individuals accessed the service during 2016-2017. Median time on
      generic PrEP was 202 days. All were MSM, 81% were white, 75% used PrEP daily and
      14% on an event-driven basis, and 67% were on generic TDF/FTC manufactured by
      Cipla Ltd. There were no serious adverse events. Thirty-nine percent of
      individuals (191/494) reported using recreational drugs in the 12 months before
      starting PrEP, and 29% (127/443) reported this while taking PrEP. During follow
      up, 26% (142/552) of individuals were diagnosed with an STI at one or more follow
      up visits. In 336 person-years of follow-up, there were no cases of HIV infection
      (0%, 95% CI 0%-1.1%). There were no new cases of hepatitis B and two new cases of
      hepatitis C. DISCUSSION: There were no new cases of HIV in 641 individuals using
      generic PrEP. At the same centre, new HIV diagnoses fell from 69 per month in
      October 2015 to 15 per month in June 2017. We believe that our support for
      individuals taking generic PrEP has contributed to this fall. There was a 10%
      increase in STI diagnoses during PrEP compared to baseline. Strategies to reduce
      STIs remain crucial.

PMID- 29057087
TI  - HIV cure research community engagement in North Carolina: a mixed-methods
      evaluation of a crowdsourcing contest.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility of using a
      crowdsourcing contest to promote HIV cure research community engagement. METHODS:
      Crowdsourcing contests are open calls for community participation to achieve a
      task, in this case to engage local communities about HIV cure research. Our
      contest solicited images and videos of what HIV cure meant to people. Contestants
      submitted entries to IdeaScale, an encrypted online contest platform. We used a
      mixed-methods study design to evaluate the contest. Engagement was assessed
      through attendance at promotional events and social media user analytics. Google
      Analytics measured contest website user-engagement statistics. Text from contest
      video entries was transcribed, coded and analysed using MAXQDA. RESULTS: There
      were 144 attendees at three promotional events and 32 entries from 39
      contestants. Most individuals who submitted entries were black (n=31), had some
      college education (n=18) and were aged 18-23 years (n=23). Social media analytics
      showed 684 unique page followers, 2233 unique page visits, 585 unique video views
      and an overall reach of 80,624 unique users. Contest submissions covered themes
      related to the community's role in shaping the future of HIV cure through
      education, social justice, creativity and stigma reduction. CONCLUSION:
      Crowdsourcing contests are feasible for engaging community members in HIV cure
      research. Community contributions to crowdsourcing contests provide useful
      content for culturally relevant and locally responsive research engagement.

PMID- 29057088
TI  - HIV cure research: print and online media reporting in Australia.
AB  - OBJECTIVES: While still in its early stages, recent scientific research towards a
      cure for HIV has generated widespread media interest. The aim of this paper was
      to explore the ways in which this research has been represented in Australian
      print and online media and discuss implications of this. METHODS: A search of
      databases from four selected media outlets was conducted to identify published
      articles that directly discussed HIV cure research. Content analysis was used to
      explore the discursive framing of HIV cure research and identify the presence or
      absence of people living with HIV in articles. RESULTS: In total, 95 articles
      were identified that had been published in print or online between 2007 and 2015.
      Media reports tended to focus on research breakthroughs or the future potential
      of HIV cure research, rather than more immediate implications of research
      findings. While not inaccurate, this focus often implied the field of HIV cure
      research was more advanced than was generally the case. There was a notable
      absence of commentary from people living with HIV or community advocates in media
      reporting. CONCLUSIONS: Media reporting may generate unrealistic expectations of
      HIV cure research. This raises ethical concerns that media reporting may
      inadvertently contribute to therapeutic or curative misconceptions among
      potential participants in HIV cure-related trials. To address this, scientists,
      HIV advocates and people living with HIV will need to work collaboratively to
      engage with reporters and media outlets to provide more consistent input and
      guidance into reporting about research towards a cure for HIV.

PMID- 29057089
TI  - Converging roads: the latest science from the 2017 IAS HIV Cure and Cancer Forum.

PMID- 29057090
TI  - Highlights from the 9th IAS Conference on HIV Science, 23-26 July 2017, Paris,
      France.

PMID- 29057091
TI  - Highlights from the BHIVA Satellite Symposium, IAS Conference, Paris, France,
      July 2017: 'Tougher times: adapting to increasing demand with declining
      resources'.

PMID- 29057092
TI  - Highlights from the 9th International Workshop on Pediatrics 21-22 July 2017,
      Paris France.

PMID- 29057093
TI  - Bone mineral density optimisation in adults with perinatally acquired HIV
      infection in routine care.

PMID- 29057094
TI  - Oral abstracts of the HIV Cure and Reservoir Symposium 2017.

PMID- 29057096
TI  - Differential KrasV12 protein levels control a switch regulating lung cancer cell
      morphology and motility.
AB  - INTRODUCTION: Oncogenic Kras mutations are important drivers of lung cancer
      development and metastasis. They are known to activate numerous cellular
      signaling pathways implicated in enhanced proliferation, survival, tumorigenicity
      and motility during malignant progression. OBJECTIVES: Most previous studies of
      Kras in cancer have focused on the comparison of cell states in the absence or
      presence of oncogenic Kras mutations. Here we show that differential expression
      of the constitutively active mutation KrasV12 has profound effects on cell
      morphology and motility that drive metastatic processes. METHODS: The study
      relies on lung cancer cell transformation models, patient-derived lung cancer
      cell lines, and human lung tumor sections combined with molecular biology
      techniques, live-cell imaging and staining methods. RESULTS: Our analysis shows
      two cell functional states driven by KrasV12 protein levels: a non-motile state
      associated with high KrasV12 levels and tumorigenicity, and a motile state
      associated with low KrasV12 levels and cell dissemination. Conversion between the
      states is conferred by differential activation of a mechano-sensitive double
      negative feedback between KrasV12/ERK/Myosin II and matrix-adhesion signaling.
      KrasV12 expression levels change upon cues such as hypoxia and integrin-mediated
      cell-matrix adhesion, rendering KrasV12 levels an integrator of micro
      environmental signals that translate into cellular function. By live cell imaging
      of tumor models we observe shedding of mixed high and low KrasV12 expressers
      forming multi-functional collectives with potentially optimal metastatic
      properties composed of a highly mobile and a highly tumorigenic unit. DISCUSSION:
      Together these data highlight previously unappreciated roles for the quantitative
      effects of expression level variation of oncogenic signaling molecules in
      conferring fundamental alterations in cell function regulation required for
      cancer progression.

PMID- 29057098
TI  - Foreword to 'Meet the Professors: Focused on Lung Cancer Precision Medicine'.

PMID- 29057097
TI  - A short discourse on vascular tissue engineering.
AB  - Vascular tissue engineering has significant potential to make a major impact on a
      wide array of clinical problems. Continued progress in understanding basic
      vascular biology will be invaluable in making further advancements. Past and
      current achievements in tissue engineering of microvasculature to perfuse organ
      specific constructs, small vessels for dialysis grafts, and modified synthetic
      and pediatric large caliber-vessel grafts will be discussed. An emphasis will be
      placed on clinical trial results with small and large-caliber vessel grafts.
      Challenges to achieving engineered constructs that satisfy the physiologic,
      immunologic, and manufacturing demands of engineered vasculature will be
      explored.

PMID- 29057095
TI  - SalmoNet, an integrated network of ten Salmonella enterica strains reveals common
      and distinct pathways to host adaptation.
AB  - Salmonella enterica is a prominent bacterial pathogen with implications on human
      and animal health. Salmonella serovars could be classified as gastro-intestinal
      or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal
      strains are closer relatives of gastro-intestinal strains than to each other
      indicating a parallel evolution of this trait. Given the complexity of the
      differences, a systems-level comparison could reveal key mechanisms enabling
      extra-intestinal serovars to cause systemic infections. Accordingly, in this
      work, we introduce a unique resource, SalmoNet, which combines manual curation,
      high-throughput data and computational predictions to provide an integrated
      network for Salmonella at the metabolic, transcriptional regulatory and protein
      protein interaction levels. SalmoNet provides the networks separately for five
      gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi
      strain database containing experimental data, SalmoNet is the first dedicated
      network resource for Salmonella. It comprehensively contains interactions between
      proteins encoded in Salmonella pathogenicity islands, as well as regulatory
      mechanisms of metabolic processes with the option to zoom-in and analyze the
      interactions at specific loci in more detail. Application of SalmoNet is not
      limited to strain comparisons as it also provides a Salmonella resource for
      biochemical network modeling, host-pathogen interaction studies, drug discovery,
      experimental validation of novel interactions, uncovering new pathological
      mechanisms from emergent properties and epidemiological studies. SalmoNet is
      available at http://salmonet.org.

PMID- 29057099
TI  - Homage to the titans of Chinese investigation and the race for lung cancer
      curability.

PMID- 29057100
TI  - Prof. Jianhua Chang: gaining a foothold in China, launching Chinese-style
      clinical trials.

PMID- 29057101
TI  - Prof. Yuan Chen: with both a benevolent heart and healing hands.

PMID- 29057102
TI  - Prof. Yun Fan: persistence guarantees expertise, patience conquers difficulties.

PMID- 29057103
TI  - Prof. Yi Hu: a doctor of acute insight and action.

PMID- 29057104
TI  - Prof. Hong Jian: dreams come true-stay true to yourself!

PMID- 29057105
TI  - Prof. Junling Li: the responsibility of a doctor.

PMID- 29057106
TI  - Prof. Anwen Liu: promoting knowledge in medicine and discipline construction,
      bring benefits to patients.

PMID- 29057107
TI  - Prof. Kewei Ma: a kind soul with a beautiful heart who lives without regrets.

PMID- 29057108
TI  - Prof. Yongqian Shu: I do my best to make patients live longer and better.

PMID- 29057109
TI  - Prof. Zhehai Wang: medicine requires great talent and high moral standards.

PMID- 29057110
TI  - Prof. Yilong Wu: a great doctor must have great virtue, and be the most
      proficient to reach supreme goodness.

PMID- 29057111
TI  - Prof. Congying Xie: early screening and diagnosis, delivering happiness.

PMID- 29057112
TI  - Prof. Li Zhang: what can serve the nation can only serve the world.

PMID- 29057113
TI  - Prof. Li Zhang, a brisk PUMCH doctor with sunshine.

PMID- 29057114
TI  - Prof. Helong Zhang: a skillful doctor loyal to his profession.

PMID- 29057115
TI  - "The doctor should doctor; the teacher should teach; the researcher should
      research"-an indepth interview with Prof. Qing Zhou.

PMID- 29057116
TI  - Prevalence of Intestinal Helminths Infestation in Children Attending Princess
      Marie Louise Children's Hospital in Accra, Ghana.
AB  - The deworming exercise program does not cover all children who are not in school.
      This study determined the prevalence and species type of helminth infestation and
      associated factors among children attending Princess Marie Louise Children's
      Hospital in Accra, Ghana. Children (225) below the age of 10 who have not taken
      antihelminthic drugs prior to the study period were recruited between May and
      June 2015. Children or guardians were interviewed using structured questionnaires
      and fresh stools were collected and processed for helminths species
      identification using microscopy. Data were analyzed using Stata version 12.
      Overall helminths infestation prevalence was 17.33% (39/225). The identified
      species were hookworm (10.22% (23/225)) and Ascaris lumbricoides (7.11%
      (16/225)). No double infestation was observed. Significant associations were
      observed between infestation and age group beyond 4 years (48 months) (aOR =
      16.72, 95% CI 1.00-279.72), place of residence (aOR = 7.35, 95% CI 1.68-32.11),
      washing hands after using toilet (0.04, 95% CI 0.01-0.20), and dirt on
      fingernails of children (7.96, 95% CI 1.73-36.65). This study demonstrates high
      prevalence of helminths parasites, hookworm, and Ascaris lumbricoides in children
      attending PMLCH. Deworming exercise should be extended to children hospitals in
      developing countries.

PMID- 29057117
TI  - A Masked, Randomized, Phase 3 Comparison of Triple Fixed-Combination
      Bimatoprost/Brimonidine/Timolol versus Fixed-Combination Brimonidine/Timolol for
      Lowering Intraocular Pressure.
AB  - OBJECTIVE: To evaluate the efficacy and safety of triple fixed-combination
      bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% (TFC) versus dual fixed
      combination brimonidine 0.2%/timolol 0.5% (DFC) in primary open-angle glaucoma
      and ocular hypertension. METHODS: Patients with intraocular pressure (IOP) >=23
      and <=34 mmHg were randomized to twice-daily TFC or DFC. The primary variable is
      the change in worse eye mean IOP from baseline at week 12 (modified intent-to
      treat (mITT) population). Secondary endpoints are mean IOP and mean change from
      baseline at weeks 1, 2, 4, 8, and 12 (mITT population). TFC superiority was
      demonstrated if the primary variable favored TFC (p <= 0.05). Sensitivity
      analyses were conducted, and safety was assessed at all visits. RESULTS: TFC (n =
      93) provided greater IOP reductions from baseline than DFC (n = 97) at week 12
      (treatment difference, 0.85 mmHg; p = 0.028) and all other visits. TFC was also
      superior to DFC in patients with high baseline IOP (i.e., IOP >= 25 mmHg; p <=
      0.011). Conjunctival hyperemia, ocular irritation, and dry eye were reported more
      often with TFC (p <= 0.016); however, discontinuations for ocular adverse events
      were similar between treatments. CONCLUSIONS: TFC demonstrated IOP-lowering
      benefits that outweigh the risk of predominantly mild ocular side effects, which
      may be particularly relevant in patients who require greater IOP lowering to
      prevent/delay disease progression. This trial is registered with
      ClinicalTrials.gov registry number: NCT01241240.

PMID- 29057118
TI  - Multiclinic Observations on the Simplified Diet in PKU.
AB  - Phenylketonuria is an inborn error of metabolism that historically has been
      treated with a strict phenylalanine-restricted diet where all foods are weighed
      and measured. This is cumbersome and difficult for patients and caregivers,
      especially patients with high phenylalanine blood concentrations who often have
      neurocognitive deficits. The Simplified Diet is an alternative approach that
      allows for increased flexibility, promotes healthy food choices, and is easier to
      manage than a traditional diet for PKU. This paper describes the implementation
      of the Simplified Diet and outlines education, counseling strategies, and
      challenges encountered by three metabolic clinics in the United States.

PMID- 29057119
TI  - Determinants of Acute Malnutrition among Children Aged 6-59 Months in Public
      Health Facilities of Pastoralist Community, Afar Region, Northeast Ethiopia: A
      Case Control Study.
AB  - BACKGROUND: In low income countries, acute malnutrition continues to be the most
      important risk factor for illnesses and deaths. The aim of this study was to
      assess the determinants of acute malnutrition among children aged 6-59 months.
      METHODS: A facility based unmatched case control study was employed on 420 (140
      cases and 280 controls) children aged 6-59 months with their caregivers between
      January 20 and February 20, 2014. Data was analyzed using SPSS version 20.0. A P
      value < 0.05 was considered statistically significant. RESULTS: Children aged 12
      23 months [AOR = 10.51, 95% CI = 4.93, 22.34], rural residence [AOR = 2.42, 95%
      CI = 1.22, 4.79], illiterate father [AOR = 2.47, 95% CI = 1.32, 4.61], Monthly
      income of less than 1000 birr [AOR = 3.98, 95% CI 2.05, 7.69], and food served
      together with family [AOR = 2.18, 95% CI = 1.10, 4.30] were associated with acute
      malnutrition. CONCLUSION: Rural residence, illiterate father, monthly income of
      less than 1000 birr, and food served together with family are statistically
      associated with acute malnutrition. Improving practices of parents on appropriate
      child feeding and creating awareness related to key risk factors of acute
      malnutrition should be further strengthened.

PMID- 29057120
TI  - IVC Measurements in Critically Ill Patients with Acute Renal Failure.
AB  - OBJECTIVE: To determine whether the inferior vena cava (IVC) measurement by
      bedside ultrasound (US-IVC) predicts improvement in renal function in patients
      with acute kidney injury (AKI). DESIGN: Prospective observational study. SETTING:
      Medical intensive care unit. PATIENTS: 33 patients with AKI were included.
      INTERVENTION: US-IVC was done on admission. The patients' management was done by
      the primary teams, who were unaware of the US-IVC findings. Two groups of
      patients were identified. Group 1 included patients who were managed in
      concordance with their US-IVC (potential volume responders who had a positive
      fluid balance at 48 h after admission and potential volume nonresponders who had
      an even or negative fluid balance at 48 hours after admission). Group 2 included
      patients in whom the fluid management was discordant with their US-IVC.
      MEASUREMENTS AND MAIN RESULTS: At 48 hours, Group 1 patients had a greater
      improvement in creatinine [85% versus 31%, p = 0.0002], creatinine clearance (78
      +/- 93% versus 8 +/- 64%, p = 0.002), and urine output (0.86 +/- 0.54 versus 0.45
      +/- 0.36 ml/Kg/h, p = 0.03). CONCLUSION: In critically ill patients with AKI,
      concurrence of fluid therapy with IVC predicted fluid management, as assessed by
      bedside ultrasound, was associated with improved renal function at 48 hours. This
      trial is registered with ClinicalTrials.gov registration number: NCT02064244.

PMID- 29057121
TI  - Triple Cultures Increase the Diagnostic Sensitivity of Mycobacterial Tuberculosis
      Empyema.
AB  - BACKGROUND: There is a continuous debate on the appropriate diagnostic approach
      and surgical management of mycobacterial empyema, with widely varied diagnostic
      practices and surgical outcomes. The aim of this study is to highlight the
      diagnostic approach and clinical features of patients who required surgical
      intervention for mycobacterial empyema. METHODS: We performed a 5-year
      retrospective cohort study of all patients with mycobacterial empyema requiring
      surgery in a single institution from November 2009 to November 2014. RESULTS:
      Eighteen patients (15 males and 3 females, median age 48.5 years) required
      surgery. Seventeen patients required decortication via posterolateral thoracotomy
      and one patient underwent video-assisted thoracic surgery drainage and pleural
      debridement. Prolonged air leak was the commonest surgical complication (50%, n =
      9). 94.4% (n = 17) had necrotizing granulomatous inflammation on histological
      examination. The sensitivity of mycobacterium smear and culture ranged between
      12.5% and 75% for pleural tissue, sputum, and pleural fluid individually. The
      combination of all 3 samples increased the diagnostic yield to 100%. CONCLUSION:
      With the implementation of pleural tissue culture at surgery, the novel
      combination of sputum, pleural fluid, and pleural tissue culture provides
      excellent diagnostic yield.

PMID- 29057122
TI  - Self-Reported Nutrition Education Received by Australian Midwives before and
      after Registration.
AB  - Educating midwives to provide nutrition advice is essential. Limited research
      focuses on midwives' nutrition education. This paper explores self-reported
      nutrition education received by Australian midwives before and after
      registration. It draws on quantitative and qualitative data from a larger online
      survey conducted with the members of the Australian College of Midwives (response
      rate = 6.9%, n = 329). Descriptive and content analyses were used. Of the
      midwives, 79.3% (n = 261) reported receiving some nutrition education during,
      before, and/or after registration. However, some described this coverage as
      limited. It lacked sufficient focus on topics such as weight management,
      nutrition assessment, and nutrition for vulnerable groups. Continuing education
      often occurred through personal initiatives, such as the midwife enrolling in
      external courses or exploring issues on the Internet and with colleagues. The
      majority of participants indicated a need for increased nutrition education
      (94.2%, n = 310) and guidelines tailored for them to provide nutrition advice
      (87.8%, n = 289). Australian midwives may not be receiving adequate nutrition
      education to provide nutrition advice. Inclusion of evidence-based nutrition
      components in midwifery education and regular updates for practising midwives
      focusing on challenging nutrition issues is required to ensure that they are
      supported in this important role.

PMID- 29057123
TI  - Four-Factor Prothrombin Complex Concentrate Reduces Time to Procedure in Vitamin
      K Antagonist-Treated Patients Experiencing Gastrointestinal Bleeding: A Post Hoc
      Analysis of Two Randomized Controlled Trials.
AB  - INTRODUCTION: To investigate the impact of a 4-factor prothrombin complex
      concentrate (4F-PCC [Beriplex(r)/Kcentra(r)]) versus plasma on "time to
      procedure" in patients with acute/severe gastrointestinal bleeding requiring
      rapid vitamin K antagonist (VKA) reversal prior to invasive procedure. METHODS: A
      post hoc analysis of two phase III trials of 4F-PCC versus plasma in patients
      with acute/severe gastrointestinal bleeding. The treatment arms were compared for
      study treatment volume, infusion times, and time from start of study treatment to
      procedure. RESULTS: Analysis included 42 patients (plasma, n = 20; 4F-PCC, n =
      22). Median (interquartile range) infusion time was significantly shorter for the
      4F-PCC group than for the plasma group (16 [13, 26] min versus 210 [149, 393]
      min; P < 0.0001). Median infusion volumes were significantly smaller (103 [80,
      130] mL versus 870 [748, 1001] mL; P < 0.0001) and median time from study
      treatment initiation to first procedure was significantly shorter in the 4F-PCC
      group than in the plasma group (17.5 [12.8, 22.8] versus 23.9 [18.5, 62.0] h; P =
      0.037). CONCLUSIONS: In this analysis of patients with acute/severe
      gastrointestinal bleeding requiring urgent VKA reversal prior to an invasive
      procedure, 4F-PCC (compared with plasma) was associated with smaller infusion
      volumes, shorter infusion times, and reduced time to procedure.

PMID- 29057124
TI  - Systems Biology Genetic Approach Identifies Serotonin Pathway as a Possible
      Target for Obstructive Sleep Apnea: Results from a Literature Search Review.
AB  - RATIONALE: Overall validity of existing genetic biomarkers in the diagnosis of
      obstructive sleep apnea (OSA) remains unclear. The objective of this systematic
      genetic study is to identify "novel" biomarkers for OSA using systems biology
      approach. METHODS: Candidate genes for OSA were extracted from PubMed, MEDLINE,
      and Embase search engines and DisGeNET database. The gene ontology (GO) analyses
      and candidate genes prioritization were performed using Enrichr tool. Genes
      pertaining to the top 10 pathways were extracted and used for Ingenuity Pathway
      Analysis. RESULTS: In total, we have identified 153 genes. The top 10 pathways
      associated with OSA include (i) serotonin receptor interaction, (ii) pathways in
      cancer, (iii) AGE-RAGE signaling in diabetes, (iv) infectious diseases, (v)
      serotonergic synapse, (vi) inflammatory bowel disease, (vii) HIF-1 signaling
      pathway, (viii) PI3-AKT signaling pathway, (ix) regulation lipolysis in
      adipocytes, and (x) rheumatoid arthritis. After removing the overlapping genes,
      we have identified 23 candidate genes, out of which >30% of the genes were
      related to the genes involved in the serotonin pathway. Among these 4 serotonin
      receptors SLC6A4, HTR2C, HTR2A, and HTR1B were strongly associated with OSA.
      CONCLUSIONS: This preliminary report identifies several potential candidate genes
      associated with OSA and also describes the possible regulatory mechanisms.

PMID- 29057125
TI  - The Effect of Aerobic Exercise on Brain-Derived Neurotrophic Factor in People
      with Neurological Disorders: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To determine the effect of aerobic exercise on brain-derived
      neurotrophic factor (BDNF) levels in people with neurological disorders. DATA
      SOURCES: Six electronic databases (CINAHL, PubMed, Cochrane, PsycINFO,
      SportDiscus, and Web of Science) were searched until the end of December 2016.
      STUDY SELECTION: Experimental or observational studies of people with
      neurological disorders who undertook an exercise intervention with BDNF as an
      outcome measure. The search strategy yielded 984 articles. DATA EXTRACTION: Study
      data were independently extracted from each article. Methodological quality of
      studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. A
      meta-analysis was planned based on the assessment of predetermined criteria. DATA
      SYNTHESIS: Eleven articles were included. Studies employed either a program of
      aerobic exercise, a single bout of aerobic exercise, or both. A meta-analysis of
      studies comparing a program of aerobic exercise against usual care/nil therapy
      showed a large effect (SMD: 0.84, 95% CI 0.47-1.20, p < 0.001) in favour of
      aerobic exercise to increase levels of BDNF. Findings for a single bout of
      aerobic exercise were mixed. Quality of studies was low (PEDro average score
      4.3/10). CONCLUSIONS: A program of aerobic exercise may contribute to increased
      levels of BDNF in neurological populations.

PMID- 29057126
TI  - Revascularization of Chronic Total Occlusion of the Infrarenal Aorta in a Patient
      with Triple Vessel Disease: Report of a Case Treated by Endovascular Approach.
AB  - Surgical management of advance aortoiliac occlusive disease is time-tested and a
      widely practiced strategy, particularly when there is significant coronary artery
      disease associated with aortoiliac occlusive disease. The technological advances
      in the field of percutaneous techniques have facilitated the use of nonsurgical
      endovascular alternatives for peripheral arterial disease in patients with
      significant comorbidities at high surgical risk, as illustrated in our case
      report. We report a case of chronic total occlusion of the aorta that was treated
      percutaneously with endovascular stenting. We also discuss the specific technique
      used in this procedure.

PMID- 29057127
TI  - Heat Stroke: A Medical Emergency Appearing in New Regions.
AB  - Heat stroke is an acute, life-threatening emergency characterized clinically by
      elevated body temperature and central nervous system dysfunction. Early
      recognition and treatment including aggressive cooling and management of life
      threatening systemic complications are essential to reduce morbidity and
      mortality. This case report describes two Danish patients diagnosed with heat
      stroke syndrome during a heat wave in the summer of 2014. Both patients were
      morbidly obese and had several predisposing illnesses. However since heat stroke
      is a rare condition in areas with temperate climate, they were not diagnosed
      until several days after admittance; hence treatment with cooling was delayed.
      Both patients were admitted to the intensive care unit, where they were treated
      with an external cooling device and received treatment for complications. Both
      cases ended fatally. As global warming continues, more heat waves will occur in
      previously cooler regions. Therefore it is important to raise awareness of heat
      stroke since outcome depends on early recognition and rapid cooling.

PMID- 29057128
TI  - Mandibular Canines with Two Roots and Two Root Canals: Case Report and Literature
      Review.
AB  - Usually, the mandibular canine only has one root and one root canal. However,
      there has been a noticeable increment in evidence showing variations in its
      morphology, such as the presence of two roots and two root canals. The aim of
      this article was to present a case of a mandibular canine with two roots and two
      root canals and to review the available literature on this anatomic variation.
      Root canal treatment of tooth #43 with such morphology was performed in a 47-year
      old woman. Careful inspection of the preoperative radiograph indicated the
      presence of more than one canal. The 12-month follow-up showed normal periapical
      tissues, with no pain or tenderness. Literature review revealed that the overall
      prevalence of such root canal configuration is 5.7%, with a strong preference for
      female sex (87.5%). Although mandibular canines with two roots and two root
      canals are not common, clinicians should always anticipate the presence of
      possible variations. Therefore, timely diagnosis and meticulous exploration of
      such mandibular canines allow for planning of an individualized treatment
      protocol, tailored to their peculiar morphology, focused on avoiding excessive
      weakening or even perforation of the roots.

PMID- 29057129
TI  - Nevus Lipomatosus Superficialis on the Left Proximal Arm.
AB  - We report a 58-year-old woman with a solitary type of nevus lipomatosus
      superficialis on the left proximal arm. To our knowledge, the occurrence of a
      solitary type of nevus lipomatosus superficialis on the arm has very rarely been
      reported. A perusal of the literature revealed but one case, to which we are
      going to add another one. Recognition of this clinical manifestation is important
      so that a proper diagnosis can be made.

PMID- 29057130
TI  - Cutaneous Vasculitis: An Unusual Presentation of a Biclonal Nodal Plasma Cell
      Dyscrasia.
AB  - We describe an unusual case of a biclonal nodal plasma cell dyscrasia, presenting
      with a vasculitic rash, end-organ damage, and cytopenias. Serum protein
      electrophoresis demonstrated a biclonal kappa-restricted paraprotein, with a
      negative skeletal survey and no bone marrow disease. Fluorodeoxyglucose-PET-CT
      (FDG-PET-CT) revealed nodal involvement, which was not appreciable clinically,
      and facilitated biopsy, confirming the diagnosis of a nodal plasmacytoma.
      Complete biochemical response and resolution of the vasculitic rash were achieved
      with bortezomib-based therapy.

PMID- 29057131
TI  - Intracranial Hemorrhage Complicating Herpes Simplex Encephalitis on Antiviral
      Therapy: A Case Report and Review of the Literature.
AB  - Herpes simplex virus (HSV) encephalitis is the most common cause of nonendemic
      sporadic encephalitis in the USA. Decreased mortality with early treatment with
      acyclovir has been documented. Although common complications include cortical
      petechial hemorrhages, frank intracerebral hematomas are considered very rare.
      Only few cases have been reported in the literature. We report a case of HSV
      encephalitis complicated by intracerebral hemorrhage 12 days after initiation of
      acyclovir therapy.

PMID- 29057132
TI  - An Atypical Porencephalic Cyst Manifesting as a Simple Partial Seizure: A Case
      Report and Literature Review.
AB  - BACKGROUND: Porencephaly is an extremely rare neurological disease characterized
      by the presence of solitary or multiple degenerative cerebrospinal fluid (CSF)
      cavities within the brain parenchyma. CASE REPORT: We describe a case involving a
      23-year-old male who presented with involuntary movements of the left upper limb
      of 6 months' duration. A diagnosis of porencephaly was confirmed by magnetic
      resonance imaging (MRI). CONCLUSION: The rarity of occurrence and atypical
      presentation of such a lesion present a challenge to clinicians. Little is known
      about the pathogenesis and appropriate management of porencephaly. Further
      studies of the implications of porencephaly for neurodevelopment and behavior are
      needed.

PMID- 29057133
TI  - A Rare Case of Recurrent Mucoepidermoid Carcinoma of the Nasal Vestibule.
AB  - We report a rare case of a large recurrent mucoepidermoid carcinoma (RMEC) in an
      81-year-old female smoker, which has originated in the right nasal vestibule. The
      recurrent tumour was inadequately treated for 6 years. It was a slow-growing
      tumour for 3 years and then began to enlarge at a higher pace. In the next three
      years it has covered a large part of the face. The patient had refused any
      medical treatment. The tumour caused breathing and swallowing difficulties.
      Because of the profuse bleeding from the tumour, the patient underwent emergency
      surgery. Surgical treatment consisted of rhinectomy and resection of the central
      upper lip and part of the right cheek. The facial defect was reconstructed
      immediately. Recovery from surgery was fast with no complications. Postoperative
      Multislice Computed Tomography scan showed no metastases so the patient did not
      receive any chemotherapy or radiotherapy. During a 2.5 years' follow-up period
      there was no recurrence of the disease.

PMID- 29057135
TI  - Rare Congenital Aberrant Left Superior Pulmonary Vein Discovered with Central
      Line Placement in a Patient with Critical Cardiorespiratory Collapse.
AB  - BACKGROUND: Partial anomalous pulmonary venous connection is a rare congenital
      vascular disorder that may be asymptomatic. Left-sided connections with the
      innominate vein are discovered infrequently and those without an atrial septal
      defect are extremely rare. CASE: A 66-year-old male was found to have an
      anomalous left pulmonary vein when a central venous catheter was inserted for
      management of hypoxemia. In addition to the connection with the left innominate
      vein an echocardiogram revealed no atrial septal defect. Computed tomography
      arteriography was used to define the anomaly. CONCLUSION: Left superior vein
      partial anomalous pulmonary venous connection with the left innominate vein was
      discovered incidentally on insertion of central venous catheter. The otherwise
      innocuous anomaly can become a significant variable when treating critical
      cardiopulmonary collapse.

PMID- 29057134
TI  - Spiral Fracture in Young Infant Causing a Diagnostic Dilemma: Nutritional Rickets
      versus Child Abuse.
AB  - Fractures are uncommon in young, nonambulatory infants. The differential
      diagnosis includes nonaccidental injury (NAI) and metabolic bone disease,
      including rickets. While rickets typically present after six months of age,
      multiple cases have been reported in younger infants. We report a case of an 11
      week-old male infant who presented with a spiral fracture of the humerus and no
      radiologic evidence of rickets. A detailed psychosocial assessment failed to
      reveal any risk factors for NAI. The patient had elevated alkaline phosphatase
      and PTH with low 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D levels.
      Additionally, the mother was noncompliant with prenatal vitamins, exclusively
      breastfeeding without vitamin D supplementation, and had markedly low vitamin D
      levels 15 weeks postpartum. The biochemical data and history were consistent with
      rickets. Given the diagnostic dilemma, the working diagnosis was rickets and the
      patient was started on ergocalciferol with subsequent normalization of his
      laboratory values and healing of the fracture. These findings are consistent with
      nutritional rickets largely due to maternal-fetal hypovitaminosis D. This case
      highlights that in young infants rickets should be considered even in the absence
      of positive radiologic findings. Additionally, it illustrates the importance of
      maintaining adequate vitamin D supplementation during pregnancy and early
      infancy.

PMID- 29057136
TI  - Prenatal and Postnatal Sonographic Confirmation of Congenital Absence of the
      Ductus Venosus in a Child with Noonan Syndrome.
AB  - The ductus venosus serves as an important vascular pathway for intrauterine
      circulation. This case presents a description of an absent ductus venosus in a
      female patient with Noonan syndrome, including both prenatal and postnatal
      imaging of the anomaly. In the setting of the anomalous vascular connection, the
      umbilical vein courses inferiorly to the iliac vein in parallel configuration
      with the umbilical artery. This finding was suspected based on prenatal imaging
      and the case was brought to attention when placement of an umbilical catheter was
      thought to be malpositioned given its appearance on radiography. Ultrasound
      imaging confirmed the anomalous course. This is in keeping with prior
      descriptions in the literature of an association between Noonan syndrome and
      aberrant umbilical venous drainage. This case illustrates the need for awareness
      of this condition by the radiologist, allowing for identification on radiographs
      and the recommendation for further confirmatory imaging. Further, the case
      illustrates the value of paying particular attention to the fetal course of the
      umbilical vessels in patients with suspected Noonan syndrome, as this population
      is particularly at risk for anomalous vasculature.

PMID- 29057137
TI  - A Large Lumbar Adnexal Neoplasm Presenting Characteristics of Eccrine Poroma and
      Poroid Hidradenoma.
AB  - Poroma is a rare benign neoplasm that derives from eccrine sweat glands
      epithelium. Its histological subtypes, with respect to its position within skin
      layers, are eccrine poroma, hidroacanthoma simplex, poroid hidradenoma, and
      dermal duct tumor. Poromas commonly exhibit benign clinical behavior as they are
      usually small and asymptomatic and do not exhibit malignant behavior. Although
      their histological subtypes share similar histological characteristics, they
      rarely coexist in the same tumor. In this report we present the case of an
      unusual poroma in terms of histological and clinical behavior as it was large and
      presented histological characteristic of both eccrine poroma and poroid
      hidradenoma. Coexistence of different histologic subtypes in the same tumor
      indicates simultaneous tumorigenesis, differentiation from one cell type to
      another, or parallel differentiation from a common progenitor cell. Implications
      in treatment remain unknown partly due to the rarity of such cases.

PMID- 29057138
TI  - Detection of Plasmodium Aldolase Using a Smartphone and Microfluidic Enzyme
      Linked Immunosorbent Assay.
AB  - BACKGROUND: Malaria control efforts are limited in rural areas. A low-cost system
      to monitor response without the use of electricity is needed. Plasmodium aldolase
      is a malaria biomarker measured using enzyme linked immunosorbent assay (ELISA)
      techniques. A three-part system using ELISA was developed consisting of a
      microfluidic chip, hand crank centrifuge, and a smartphone. METHODS: A circular
      microfluidic chip was fabricated using clear acrylic and a CO2 laser. A series of
      passive valves released reagents at precise times based upon centrifugal force.
      Color change was measured via smartphone camera using an application programmed
      in Java. The microchip was compared to a standard 96-well sandwich ELISA.
      RESULTS: Results from standard ELISA were compared to microchip at varying
      concentrations (1-10 ng/mL). Over 15 different microfluidic patterns were tested,
      and a final prototype of the chip was created. The prototype microchip was
      compared to standard sandwich ELISA (n = 20) using samples of recombinant
      aldolase. Color readings of standard ELISA and microfluidic microchip showed
      similar results. CONCLUSION: A low-cost microfluidic system could detect and
      follow therapeutic outcomes in rural areas and identify resistant strains.

PMID- 29057139
TI  - Comparison Study of Voltammetric Behavior of Muscle Relaxant Dantrolene Sodium on
      Silver Solid Amalgam and Bismuth Film Electrodes.
AB  - Voltammetric behavior of muscle relaxant dantrolene sodium (DAN) was studied and
      the voltammetric methods for its determination using polished and mercury
      meniscus modified silver solid amalgam electrodes (p-AgSAE and m-AgSAE) as well
      as using bismuth film electrode (BiFE, ex situ plating on GCE) have been
      proposed. These working electrodes represent the most commonly used alternatives
      to mercury ones which come wrongfully into disfavor because of alleged toxicity
      of mercury. Within this work, the obtained results of DAN determination have been
      completed by corresponding statistical parameters and also some electrochemical
      characteristics of AgSAEs and BiFE were assessed, especially in comparison with
      the mercury electrodes.

PMID- 29057140
TI  - Quality of Ceftriaxone Sodium in Lyophilized Powder for Injection Evaluated by
      Clean, Fast, and Efficient Spectrophotometric Method.
AB  - Ceftriaxone sodium, an antimicrobial agent that plays an important role in
      clinical practice, is successfully used to treat infections caused by most Gram
      positive and Gram-negative organisms. Since there are few rapid analytical
      methods for ceftriaxone analysis to use in the pharmaceutical routine, the aim of
      this research was to develop a new method able to quantify this cephalosporin.
      Therefore, a sensitive, rapid, simple UV spectrophotometric method for the
      determination and quantification of ceftriaxone sodium was proposed. The UV
      detector was set at 241 nm. Beer's law obeyed the concentration range of 10-20 ug
      mL-1. Statistical comparison of the results with a well-established reported
      method showed excellent agreement and proved that there is no significant
      difference in the accuracy and precision. Intra- and interday variability for the
      method were less than 2% relative standard deviation. The proposed method was
      applied to the determination of the examined drugs in pharmaceutical formulations
      and the results demonstrated that the method is equally accurate, precise, and
      reproducible as the official methods.

PMID- 29057141
TI  - Transfer and Metabolism of Triadimefon Residues from Rape Flowers to Apicultural
      Products.
AB  - This paper presents a study on the transfer and metabolism of triadimefon
      residues from rape flowers to apicultural products. In the field trials, honeybee
      colonies were placed in four rape greenhouses treated with triadimefon on
      standard dosage. Apicultural products (pollen, honey, and royal jelly) were
      collected on a regular basis. Sample preparation and extraction procedure were
      established. HPLC/ESI-MS/MS method was validated. The respective residues of
      triadimefon and metabolite triadimenol were 0.03 +/- 0.002 mg/kg and 0.13 +/-
      0.02 mg/kg in pollen on the 18th day, and both had reached the limits of
      detection in honey on the 24th day, while they were 0.004 +/- 0.0005 mg/kg and
      0.010 +/- 0.0002 mg/kg in royal jelly on the 22nd day. Mathematical curve fitting
      studies were further investigated. On the basis of recommended dosage, the
      degradation half-lives of triadimefon in pollen, honey, and royal jelly were
      about 0.7, 12.5, and 19.5 days, respectively. Transfer of triadimefon residues
      from rape flowers to apicultural products diminished over spraying time. The
      residues of triadimefon and metabolite triadimenol in pollen were about 10 times
      higher than those in honey and jelly. Time to attain the maximum permissible
      limit of pollen in the European Union was 14.9 days, predicted from the index
      function.

PMID- 29057142
TI  - Design and Validation of a Torque Dense, Highly Backdrivable Powered Knee-Ankle
      Orthosis.
AB  - This paper presents the mechatronic design and experimental validation of a novel
      powered knee-ankle orthosis for testing torque-driven rehabilitation control
      strategies. The modular actuator of the orthosis is designed with a torque dense
      motor and a custom low-ratio transmission (24:1) to provide mechanical
      transparency to the user, allowing them to actively contribute to their joint
      kinematics during gait training. The 4.88 kg orthosis utilizes frameless
      components and light materials, such as aluminum alloy and carbon fiber, to
      reduce its mass. A human subject experiment demonstrates accurate torque control
      with high output torque during stance and low backdrive torque during swing at
      fast walking speeds. This work shows that backdrivability, precise torque
      control, high torque output, and light weight can be achieved in a powered
      orthosis without the high cost and complexity of variable transmissions,
      clutches, and/or series elastic components.

PMID- 29057143
TI  - Phytotherapy of High Blood Pressure in Three Phytogeographic Regions of Cameroon.
AB  - OBJECTIVE: High blood pressure is a public health challenge worldwide. According
      to World Health Organization, 30% of men and 50% of women 65 to 75 years old are
      suffering from high blood pressure. The number of hypertensive patients in the
      world will attain 1.56 billion of people, with 60% increase in prevalence. The
      incidence of high blood pressure increases with age, but nowadays, is being
      noticed an increasing incidence in young people. The socio-cultural medicine may
      provide new solutions in the management of this pathology. Therefore this study
      was carried out to record and document plants used against high blood pressure in
      socio-cultural medicine for future drugs discovery worldwide. METHODS: An ethno
      botanical survey was realized between 2002 and 2016 to identify manifold plants
      used to fight against high blood pressure. This survey was carried out in three
      phytogeographic regions of Cameroon. Amongst people living in those regions, 1131
      randomly screened interviewees distributed in 58 socio-cultural groups were
      involved in this study. RESULTS: This survey reveals that about 70% of
      interviewees don't know high blood pressure which is a symptomless disease. A
      total of 28 species of plants were recorded. These plants belong to 25 genera and
      24 families. They were used to prepare 28 herbal remedies for the treatment of
      high blood pressure. In the morphological point of view about 10/28 (36%) plants
      are herbs; 9/28 (32%) plants are trees and 9/28 (32%) plants are shrubs. Only
      3/28 plants (11%) used including Allium sativum, Aloe barteri and Aloe buttneri)
      are cultivated. This means that the plants used in this study don't usually have
      some form of protection through cultivation which is encouraging in terms of
      their conservation. CONCLUSION: The uncontrolled use of a hypotensive plants can
      provoke a fatal hypotension in hypertensive patients. Therefore the use of
      hypotensive plants needs to be controlled by physician or by a patient
      verification using a blood pressure monitor. Recorded species which will slow the
      high blood pressure will be used for the preparation of phytodrugs.

PMID- 29057144
TI  - Detection and Separation of Inorganic Cations in Natural, Potable, and Wastewater
      Samples Using Capillary Zone Electrophoresis with Indirect UV Detection.
AB  - Capillary zone electrophoresis (CZE) is a sensitive and rapid technique for
      determining traces of inorganic cations in water samples. CZE with indirect UV
      diode array detection (CZE-DAD) was utilized to identify several inorganic
      cations in natural, potable, and wastewater samples. A pH 4.35 background
      electrolyte system was employed and consisted of 15 mM imidazole, 8 mM malonic
      acid, 2 mM 18-crown-6 ether as complexing agents, 10% v/v methanol as an organic
      modifier with indirect absorbance reference at 214 nm. The CZE method involved
      electromigration injection at 5 kV for 5 s, a separation voltage of 20 kV at 25
      degrees C, and a detection wavelength of 280 nm. Six main cations (ammonium
      [Formula: see text], potassium K+, calcium Ca2+, sodium Na+, magnesium Mg2+, and
      lead Pb2+) were tested, and all but lead, were detected in the water samples at
      concentrations between 0.03 and 755 ppm with a detection limit ranging between
      0.023 and 0.084 ppm. The successful evaluation of the proposed methodology
      allowed us to reliably detect and separate six metal ions in different water
      samples without any pretreatment. All water samples were collected from Northern
      New York towns and the Raquette River water system, the third longest river in
      New York State and the largest watershed of the central and western Adirondacks.

PMID- 29057145
TI  - Detection and Quantification of Inorganic and Organic Anions in Natural, Potable,
      and Wastewaters in Northern New York Using Capillary Zone Electrophoresis and
      Indirect UV Detection.
AB  - Capillary zone electrophoresis (CZE) is a sensitive and rapid technique used for
      determining traces of inorganic and organic anions in potable, natural, and
      wastewaters. Here, CZE with indirect UV-diode array detection (CZE-DAD) was
      employed with a background electrolyte system comprising of an Agilent
      Technologies proprietary basic anion buffer at pH 12.0 and a forensic anion
      detection method. The limits of detection (LOD) for this method ranged between 3
      and 5 ppm and involved hydrodynamic injection of 50 mbar for 6 s with a negative
      polarity separation voltage of -30 kV at 30 degrees C, a detection wavelength of
      350 nm and indirect reference of 275 nm. Fourteen different anions were checked
      for in the water samples that were examined and included bromide, chloride,
      thiosulfate, nitrate, nitrite, sulfate, azide, carbonate, fluoride, arsenate,
      phosphate, acetate, lactate, and silicate. The water samples were collected from
      Northern New York towns and the Raquette River water system, the third longest
      river in New York State and the largest watershed of the central and western
      Adirondacks. The concentrations detected for these anions ranged from <5.0 ppm to
      260 ppm.

PMID- 29057146
TI  - Light scattering spectroscopy identifies the malignant potential of pancreatic
      cysts during endoscopy.
AB  - Pancreatic cancers are usually detected at an advanced stage and have poor
      prognosis. About one fifth of these arise from pancreatic cystic lesions. Yet not
      all lesions are precancerous, and imaging tools lack adequate accuracy for
      distinguishing precancerous from benign cysts. Therefore, decisions on surgical
      resection usually rely on endoscopic ultrasound-guided fine needle aspiration
      (EUS-FNA). Unfortunately, cyst fluid often contains few cells, and fluid chemical
      analysis lacks accuracy, resulting in dire consequences, including unnecessary
      pancreatic surgery for benign cysts and the development of cancer. Here, we
      report an optical spectroscopic technique, based on a spatial gating fibre-optic
      probe, that predicts the malignant potential of pancreatic cystic lesions during
      routine diagnostic EUS-FNA procedures. In a double-blind prospective study in 25
      patients, with 14 cysts measured in vivo and 13 postoperatively, the technique
      achieved an overall accuracy of 95%, with a 95%confidence interval of 78-99%, in
      cysts with definitive diagnosis.

PMID- 29057149
TI  - Rate and Predictors of Endoscopic Mucosal Healing in Biologic Naive Patients with
      Inflammatory Bowel Disease by Azathioprine Treatment: A Real World, 10 Years'
      Experience from a Single Centre in Turkey.
AB  - BACKGROUND: There is increasing evidence that endoscopic mucosal healing (EMH) is
      a key target in inflammatory bowel disease (IBD) therapy. However, there is
      limited evidence of EMH rates with conventional IBD therapy outside of Western
      population groups. AIM: To evaluate the role of azathioprine (AZA) in inducing
      EMH in IBD patients. METHODS: Patients with inflammatory bowel disease were
      evaluated in terms of endoscopic mucosal healing and the incidence of surgical
      interventions during the azathioprine treatment between 1995 to 2014. RESULTS: A
      total of 120 inflammatory bowel disease patients were enrolled. Endoscopic
      mucosal healing was found in 37% patients with inflammatory bowel disease (42% in
      chronic ulcerative colitis and 33% in Crohn's disease). Male gender had a
      negative impact on the efficacy of azathioprine (P<0.05). Responder inflammatory
      bowel disease patients were older (age at the IBD diagnose) than the nonresponder
      (P<0.05). Azathioprine therapy reduced the number of the surgical interventions
      (P<0.05). CONCLUSION: We showed that azathioprine therapy significantly induced
      endoscopic mucosal healing in biologic naive patients with active inflammatory
      bowel disease as well as decreasing the surgical interventions, with negative
      predictive factors identified by a younger age at IBD presentation and male
      gender.

PMID- 29057147
TI  - Microscale arrays for the profiling of start and stop signals coordinating human
      neutrophil swarming.
AB  - Neutrophil swarms protect healthy tissues by sealing off sites of infection. In
      the absence of swarming, microbial invasion of surrounding tissues can result in
      severe infections. Recent observations in animal models have shown that swarming
      requires rapid neutrophil responses and well-choreographed neutrophil migration
      patterns. However, in animal models physical access to the molecular signals
      coordinating neutrophil activities during swarming is limited. Here, we report
      the development and validation of large microscale arrays of zymosan-particle
      clusters for the study of human neutrophils during swarming ex vivo. We
      characterized the synchronized swarming of human neutrophils under the guidance
      of neutrophil-released chemokines, and measured the mediators released at
      different phases of human-neutrophil swarming against targets simulating
      infections. We found that the network of mediators coordinating human-neutrophil
      swarming includes start and stop signals, proteolytic enzymes and enzyme
      inhibitors, as well as modulators of activation of other immune and non-immune
      cells. We also show that the swarming behavior of neutrophils from patients
      following major trauma is deficient and gives rise to smaller swarms than those
      of neutrophils from healthy individuals.

PMID- 29057150
TI  - Psychological Effects of Urban Crime Gleaned from Social Media.
AB  - Exposure to frequent crime incidents has been found to have a negative bearing on
      the well-being of city residents, even if they are not themselves a direct
      victim. We pursue the research question of whether naturalistic data shared on
      Twitter may provide a "lens" to understand changes in psychological attributes of
      urban communities (1) immediately following crime incidents, as well as (2) due
      to long-term exposure to crime. We analyze half a million Twitter posts from the
      City of Atlanta in 2014, where the rate of violent crime is three times of the
      national average. In a first study, we develop a statistical method to detect
      changes in social media psychological attributes in the immediate aftermath of a
      crime event. Second, we develop a regression model that uses historical
      (yearlong) crime to predict Twitter negative emotion, anxiety, anger, and
      sadness. We do not find significant changes in social media affect immediately
      following crime in Atlanta. However we do observe significant ability of
      historical crime to account for heightened negative emotion and anger in the
      future. Our findings have implications in gauging the utility of social media to
      infer longitudinal and population-scale patterns of urban well-being.

PMID- 29057151
TI  - A Comprehensive Assessment of Four Options for Financing Health Care Delivery in
      Oregon.
AB  - This article describes four options for financing health care for residents of
      the state of Oregon and compares the projected impacts and feasibility of each
      option. The Single Payer option and the Health Care Ingenuity Plan would achieve
      universal coverage, while the Public Option would add a state-sponsored plan to
      the Affordable Care Act (ACA) Marketplace. Under the Status Quo option, Oregon
      would maintain its expansion of Medicaid and subsidies for nongroup coverage
      through the ACA Marketplace. The state could cover all residents under the Single
      Payer option with little change in overall health care costs, but doing so would
      require cuts to provider payment rates that could worsen access to care, and
      implementation hurdles may be insurmountable. The Health Care Ingenuity Plan, a
      state-managed plan featuring competition among private plans, would also achieve
      universal coverage and would sever the employer-health insurance link, but the
      provider payment rates would likely be set too high, so health care costs would
      increase. The Public Option would be the easiest of the three options to
      implement, but because it would not affect many people, it would be an
      incremental improvement to the Status Quo. Policymakers will need to weigh these
      options against their desire for change to balance the benefits with the trade
      offs.

PMID- 29057148
TI  - Postural Tremor and Ataxia Progression in Spinocerebellar Ataxias.
AB  - BACKGROUND: Postural tremor can sometimes occur in spinocerebellar ataxias
      (SCAs). However, the prevalence and clinical characteristics of postural tremor
      in SCAs are poorly understood, and whether SCA patients with postural tremor have
      different ataxia progression is not known. METHODS: We studied postural tremor in
      315 patients with SCA1, 2, 3, and 6 recruited from the Clinical Research
      Consortium for Spinocerebellar Ataxias (CRC-SCA), which consists of 12
      participating centers in the United States, and we evaluated ataxia progression
      in these patients from January 2010 to August 2012. RESULTS: Among 315 SCA
      patients, postural tremor was most common in SCA2 patients (SCA1, 5.8%; SCA2,
      27.5%; SCA3, 12.4%; SCA6, 16.9%; p = 0.007). SCA3 patients with postural tremor
      had longer CAG repeat expansions than SCA3 patients without postural tremor
      (73.67 +/- 3.12 vs. 70.42 +/- 3.96, p = 0.003). Interestingly, SCA1 and SCA6
      patients with postural tremor had a slower rate of ataxia progression (SCA1, beta
      = -0.91, p < 0.001; SCA6, beta = -1.28, p = 0.025), while SCA2 patients with
      postural tremor had a faster rate of ataxia progression (beta = 1.54, p = 0.034).
      We also found that the presence of postural tremor in SCA2 patients could be
      influenced by repeat expansions of ATXN1 (beta = -1.53, p = 0.037) and ATXN3
      (beta = 0.57, p = 0.018), whereas postural tremor in SCA3 was associated with
      repeat lengths in TBP (beta = 0.63, p = 0.041) and PPP2R2B (beta = -0.40, p =
      0.032). DISCUSSION: Postural tremor could be a clinical feature of SCAs, and the
      presence of postural tremor could be associated with different rates of ataxia
      progression. Genetic interactions between ataxia genes might influence the brain
      circuitry and thus affect the clinical presentation of postural tremor.

PMID- 29057152
TI  - Modeling Dr. Dynasaur 2.0 Coverage and Finance Proposals: Effects of the
      Expansion of Vermont's Dr. Dynasaur Program to All Individuals Through Age 25.
AB  - The authors assessed an expansion of Vermont's Dr. Dynasaur program that would
      cover all residents age 25 and younger. The current Dr. Dynasaur program combines
      Vermont's Medicaid program and Child Health Insurance Program for children ages 0
      through 18 to provide a seamless insurance program for those with family incomes
      below 317 percent of the federal poverty level. The authors used RAND's COMPARE
      VT microsimulation model with Vermont-specific demographic, economic, and
      actuarial data to estimate the effects on health insurance coverage, costs, and
      premiums. They also identified the new revenues required to fund the program
      expansion and explored three alternative financing strategies to raise those
      funds: (1) an increase in the Vermont income tax, (2) a Vermont payroll tax, and
      (3) a Vermont business enterprise tax. The authors found that enrollment would
      increase by more than 260 percent under the 100-percent enrollment scenario and
      by nearly 200 percent under the 70-percent enrollment scenario by 2019. Not
      surprisingly, the children and young adults who move off employer-sponsored
      insurance (ESI) and into Dr. Dynasaur 2.0 have considerably lower expected health
      care costs than those who remain on ESI, increasing the per-person premiums by
      nearly $1,000 for those remaining enrolled in ESI. Annual health care
      expenditures per person for children and young adults in 2019 are estimated at
      $4,325 with Medicare prices. The combination of increased reimbursement rates,
      large increases in enrollment, and relatively low Dr. Dynasaur premiums (no more
      than $720 per year) will require significant new tax revenues to meet program
      obligations.

PMID- 29057153
TI  - Testing New Codes to Capture Post-Operative Care.
AB  - The Centers for Medicare & Medicaid Services (CMS) uses the resource-based
      relative value system to determine payment for physicians and nonphysician
      practitioners for their professional services. For many surgeries and other types
      of procedures, Medicare payment includes pre- and post-operative visits delivered
      during a global period of 10 or 90 days. Congress mandated that CMS collect data
      on the "number and level" of visits in the global period from a representative
      sample of physicians beginning January 1, 2017. At CMS's request, RAND developed
      a new set of nonpayment codes that could be used to capture the number and level
      of visits. In July 2016, CMS issued a proposed rule that included a slightly
      modified version of the codes developed by RAND and proposed to require their use
      by practitioners. Given that these codes had never been tested or used by
      practitioners, CMS asked RAND to pilot the proposed codes to determine whether
      practitioners understood and could accurately apply the codes. RAND's approach
      was to create a series of vignettes and to test the use of these vignettes using
      semi-structured interviews with a small set of physicians, followed by more
      extensive testing through surveys with a larger group of physicians. This study
      provides recommendations on how to use vignettes to test new codes and uncover
      questions about such codes. Such input could be used to help refine instructions
      for using codes, as well as to potentially refine the codes themselves.

PMID- 29057154
TI  - A Psychometric Study of the Modified Bridges for Newborns Screening Tool.
AB  - Welcome Baby, a program that First 5 Los Angeles (First 5 LA) sponsors, provides
      new mothers with supportive services intended to create enriching environments
      for their children. To identify mothers in need of these services, First 5 LA
      employs hospital liaisons who administer a maternal risk assessment tool, the
      Modified Bridges for Newborns screening tool, during postpartum interviews of
      mothers. First 5 LA uses risk assessment scores from the Modified Bridges to
      classify mothers as low, moderate, or high risk; high-risk mothers are eligible
      for additional supportive services that are not available to low- and moderate
      risk mothers. This article describes RAND Corporation work evaluating the
      psychometric characteristics of the Modified Bridges.

PMID- 29057155
TI  - An Agenda to Advance Integrative Resilience Research and Practice: Key Themes
      From a Resilience Roundtable.
AB  - People are facing an increasing variety and number of stressors, ranging from
      interpersonal difficulties to environmental hazards and societal forces.
      Resilience is the process of, capacity for, or outcome of adapting well in the
      face of adversity, trauma, tragedy, threats, or significant sources of stress.
      The science of resilience has advanced greatly since 2000, but there is an
      increasing recognition of the need for researchers and practitioners from
      different disciplines and sectors to work better together on this topic and for a
      shared agenda for promoting transdisciplinary resilience research. The study
      provides a path forward, primarily built on proceedings from a Resilience
      Roundtable, held in June 2016, and supplemented with relevant literature review.
      The Resilience Roundtable brought together researchers, practitioners, and
      policymakers, across disciplines and sectors for a daylong discussion of where
      and how we can move to a more integrated and cohesive resilience agenda, with
      attention to critical factors that would motivate more collaborative work. The
      roundtable identified priorities for advancing a shared resilience agenda and
      made ten recommendations for implementing it.

PMID- 29057156
TI  - Improving Outcomes for Children Exposed to Violence: Safe Start Promising
      Approaches.
AB  - Children's exposure to violence is common and can lead to mental health problems
      and delinquent behaviors. Because many interventions have focused on specific
      violence types or symptoms and been difficult to implement in real-world
      settings, the evidence base is still emerging. The Office of Juvenile Justice and
      Delinquency Prevention's Safe Start Promising Approaches (SSPA) initiative
      focused on preventing and reducing the impact of children's exposure to violence
      through interventions in ten diverse communities. The evaluation examined the
      effectiveness of the SSPA interventions to address issues for children and
      families exposed to violence. The ten sites were diverse in their intervention
      approaches, types of violence exposure targeted, and implementation settings. To
      evaluate each approach's effectiveness in reducing violence's harmful effects,
      RAND researchers partnered with the community-based sites to develop a rigorous
      controlled evaluation design for each intervention, with either a randomized
      control group or a comparison group selected on similar characteristics. The
      longitudinal analyses found that families in both the intervention and comparison
      groups had positive gains on many outcomes, but there was no evidence that the
      intervention groups improved more. Among those who received Safe Start services,
      one site produced large, significant improvements in posttraumatic stress
      disorder symptoms, and another site produced medium, significant effects on
      several outcomes (child self-control, posttraumatic stress disorder, and
      behavior; caregiver depression; and family conflict). Although the initiative
      added to knowledge about how to address the problem, there was no clear case for
      using a particular intervention to help these children and their families.

PMID- 29057157
TI  - The Air Force Deployment Transition Center: Assessment of Program Structure,
      Process, and Outcomes.
AB  - It is often accepted as common knowledge that military personnel benefit from
      decompression time between a war zone and the home station. To capitalize on the
      potential benefits of a decompression period paired with support services, the
      U.S. Air Force established the Deployment Transition Center (DTC) at Ramstein Air
      Base in Germany in July 2010. The DTC provides airmen returning from combat
      missions with an opportunity to decompress and share lessons learned before
      returning to their home stations. The authors of this study evaluate the
      structure, processes, and outcomes of the DTC program. They find that, although a
      majority of participants found the DTC program worthwhile, a comparison of DTC
      participants and similar airmen who did not participate the program shows no
      evidence that the program helps reduce posttraumatic stress disorder symptoms,
      depressive symptoms, binge drinking, or social conflicts with family and
      coworkers. In addition, one of the DTC program elements appears to be similar to
      posttraumatic debriefing interventions, which several studies have found to be
      either ineffective or harmful. For these reasons, if the main goals of the DTC
      program are to improve behavioral health and social conflict outcomes, the
      authors recommend that the DTC program be discontinued or redesigned and Air
      Force resources invested in alternative programs. However, if the DTC program has
      other goals, such as providing rest and relaxation to airmen after a difficult
      deployment or capturing after-action information, then the authors recommend that
      these goals be documented and the DTC program be more specifically tailored to
      them.

PMID- 29057158
TI  - Preventing, Identifying, and Treating Prescription Drug Misuse Among Active-Duty
      Service Members.
AB  - Prescription drug misuse (PDM) is of critical concern for the military because of
      its potential impact on military readiness, the health and well-being of military
      personnel, and associated health care costs. The purpose of this study is to
      summarize insights gleaned from a series of activities that the RAND Corporation
      undertook for the Deputy Assistant Secretary of Defense for Readiness to address
      this important health and military readiness issue. The authors completed a
      review of U.S. Department of Defense policies and a comprehensive literature
      review of clinical guidelines and the empirical literature on the prevention and
      treatment of PDM and conducted individual face-to-face interviews with 66 health
      and behavioral health care providers at nine medical treatment facilities across
      three regions within the contiguous United States to identify best practices in
      the prevention, identification, and treatment of PDM and the extent to which
      those practices are known and followed. The study also presents the framework of
      an analytic tool that, once informed by data available to the military but not
      available to the authors, can assist the military in predicting future trends in
      PDM based on current demographics of active-duty service members and rates of
      injury and prescribing of prescription drugs. The findings from this work led the
      authors to formulate a set of key insights that they believe might improve the
      rapid identification and treatment of service members dealing with PDM, thereby
      improving future force readiness.

PMID- 29057159
TI  - Supporting Veterans in Massachusetts: An Assessment of Needs, Well-Being, and
      Available Resources.
AB  - Massachusetts is home to approximately 380,000 of the nation's more than 21
      million veterans, but there has been little research on the resources available
      to this population at the state level. There are numerous resources available to
      veterans and other military-affiliated groups in Massachusetts, but there are
      still pockets of unmet need in the areas of education, employment, health care,
      housing, financial, and legal services-particularly for newer veterans and
      current National Guard/reserve members. Although Massachusetts veterans fare
      better overall than their peers in other states, they lag behind other
      Massachusetts residents in terms of health and financial status. Massachusetts
      veterans and National Guard/reserve members who need support and services face
      such barriers as a lack of knowledge about how to access services, a lack of
      awareness about eligibility, and geographic distance from service providers. As
      the veteran population changes both nationally and in Massachusetts, it will be
      important for public- and private-sector providers serving Massachusetts veterans
      and service members to continue addressing unmet needs while ensuring that
      resources are responsive to shifts in these populations. A better understanding
      of the unique needs of Massachusetts veterans can help inform investments in
      initiatives that target these populations and guide efforts to remedy barriers to
      accessing available support services and other resources.

PMID- 29057160
TI  - A General Agent-Based Model of Social Learning.
AB  - When engaging in behaviors that may entail risks or outcomes that are unknown or
      uncertain, individuals often look beyond their own experiences (including past
      behaviors and subsequent outcomes) to consider the experiences of others in their
      immediate social networks. This social influence at the micro-scale (i.e., the
      way in which individuals are influenced by their immediate social networks) can
      affect change in the greater social web in such a way that social networks may
      have profound effects on decisionmaking at the population level. Such micro-level
      social influence is central to many theories of individual decisionmaking and
      behavior. Observations of population-level dynamics at the macro-level
      demonstrate the end result of these processes-for example, over time, people's
      behavior tends to look more like that of their peers. This article describes a
      general agent-based model (ABM) for studying social influence, and uses that
      general ABM to explore the relationship between micro-influence and macro
      dynamics for broad classes of problems. We also describe an approach to tailor
      the general ABM to model a specific behavior influenced by social learning, which
      we illustrate using surveys designed to inform the ABM. The framework we
      developed could be useful for studying any system in which social learning may
      occur. But while our general ABM can produce dynamics reminiscent of those that
      might result from many different types of behaviors, it will typically need to be
      tailored when used to model any particular behavior.

PMID- 29057161
TI  - Letter from the Editor.

PMID- 29057162
TI  - Augmenting Endogenous Levels of Retinal Annexin A1 Suppresses Uveitis in Mice.
AB  - PURPOSE: The purpose of this study was to examine the expression of the anti
      inflammatory protein Annexin A1 (AnxA1) in mice and human retinae during uveitis
      and to determine whether local administration of human recombinant AnxA1
      (hrAnxA1) can suppress uveitis in mice. METHODS: Retinal sections from mice
      (healthy normal and uveitis) and postmortem human (no history of eye disease (n =
      5) and uveitis (n = 7)) were stained for AnxA1 expression and imaged by
      immunofluorescence microscopy. AnxA1 cellular expression was determined by
      colabeling with CD45, glial fibrillary acidic protein (GFAP), and Iba-1 cells,
      with additional staining of AnxA1 receptors formyl peptide receptor 1 (FPR1) and
      FPRL1/FPR2. Mice with acute endotoxin-induced uveitis and chronic experimental
      autoimmune uveitis were treated locally by intravitreal injection with hrAnxA1,
      and disease was assessed by clinical scoring and quantification of leukocyte
      infiltrate via flow cytometry. RESULTS: Constitutive expression of AnxA1 was
      observed in both healthy mouse and human retinae, and its expression increased
      during uveitis compared to healthy controls. AnxA1 colocalizes predominantly with
      CD45+ cells, GFAP+ macroglia, and to a lesser extent, Iba-1+ myeloid cells. We
      also demonstrate that local treatment with hrAnxA1 attenuates the severity of
      uveitis in mice. CONCLUSIONS: These data indicate that locally expressed AnxA1 is
      elevated in the retina during intraocular inflammation. We demonstrate that local
      administration of hrAnxA1 to augment levels results in suppression of uveitis in
      mice. TRANSLATIONAL RELEVANCE: Our data suggest that elevated expression of
      retinal AnxA1 in human uveitis may be immunoregulatory and that local
      supplementation with hrAnxA1 may provide a potential novel treatment for
      inflammatory eye diseases such as noninfectious uveitis.

PMID- 29057163
TI  - Characterization of Long Working Distance Optical Coherence Tomography for
      Imaging of Pediatric Retinal Pathology.
AB  - PURPOSE: We determined the feasibility of fovea and optic nerve head imaging with
      a long working distance (LWD) swept source optical coherence tomography (OCT)
      prototype in adults, teenagers, and young children. METHODS: A prototype swept
      source OCT system with a LWD (defined as distance from the last optical element
      of the imaging system to the eye) of 350 mm with custom fixation targets was
      developed to facilitate imaging of children. Imaging was performed in 49
      participants from three age groups: 26 adults, 16 children 13 to 18 years old
      (teenagers), and seven children under 6 years old (young children) under an
      approved institutional review board protocol. The imaging goal was to acquire
      high quality scans of the fovea and optic nerve in each eye in the shortest time
      possible. OCT B-scans and volumes of the fovea and optic nerve head of each
      eligible eye were captured and graded based on four categories (lateral and axial
      centration, contrast, and resolution) and on ability to determine presence or
      absence of pathology. RESULTS: LWD-OCT imaging was successful in 88 of 94
      eligible eyes, including seven of 10 eyes of young children. Of the successfully
      acquired OCT images, 83% of B-scan and volumetric images, including 86% from
      young children, were graded as high-quality scans. Pathology was observed in high
      quality OCT images. CONCLUSIONS: The prototype LWD-OCT system achieved high
      quality retinal imaging of adults, teenagers, and some young children with and
      without pathology with reasonable alignment time. TRANSLATIONAL RELEVANCE: The
      LWD-OCT system can facilitate imaging in children.

PMID- 29057164
TI  - Long-Term Chamomile Therapy of Generalized Anxiety Disorder: A Study Protocol for
      a Randomized, Double-Blind, Placebo- Controlled Trial.
AB  - BACKGROUND: Anxiety symptoms are among the most common reasons for consumers to
      use Complementary and Alternative Medicine (CAM) therapy. Although many
      botanicals have been proposed as putative remedies for anxiety symptoms, there
      has been a paucity of controlled trials of these remedies. A preliminary study of
      the anxiolytic effect of Chamomile (Matricaria recutita) in humans suggests that
      chamomile may have anxiolytic and antidepressant activity. We now seek to conduct
      a 5-year randomized, double-blind, placebo-substitution study to examine the
      short and long-term safety and efficacy of chamomile extract in Generalized
      Anxiety Disorder (GAD). METHODS/DESIGN: 180 subjects with moderate to severe GAD
      will receive initial open-label pharmaceutical-grade chamomile extract 500-1,500
      mg daily for 8 weeks. Responders to treatment who remain well for an additional 4
      weeks of consolidation therapy, will be randomized to double-blind continuation
      therapy with either chamomile extract 500-1,500 mg daily or placebo for an
      additional 26 weeks. The primary outcome will be the time to relapse during study
      continuation therapy in each treatment condition. Secondary outcomes will include
      the proportion of subjects in each treatment condition who relapse, as well as
      the proportion of subjects with treatment-emergent adverse events. Quality of
      life ratings will also be compared between treatment conditions during short and
      long-term therapy. DISCUSSION: Many individuals with mental disorders decline
      conventional therapy and seek CAM therapies for their symptoms. Thus, the
      identification of effective CAM therapy is of relevance to reducing the burden of
      mental illness. This study builds upon our prior findings of significant
      superiority of chamomile versus placebo in reducing GAD symptoms. We now extend
      these preliminary findings by conducting a randomized long-term safety and
      efficacy study of chamomile in GAD.

PMID- 29057165
TI  - Mechanisms of Fibroblast Activation in the Remodeling Myocardium.
AB  - PURPOSE OF REVIEW: Activated fibroblasts are critically implicated in repair and
      remodeling of the injured heart. This manuscript discusses recent progress in the
      cell biology of fibroblasts in the infarcted and remodeling myocardium,
      highlighting advances in understanding the origin, function and mechanisms of
      activation of these cells. RECENT FINDINGS: Following myocardial injury,
      fibroblasts undergo activation and myofibroblast transdifferentiation. Recently
      published studies have suggested that most activated myofibroblasts in the
      infarcted and pressure-overloaded hearts are derived from resident fibroblast
      populations. In the healing infarct, fibroblasts undergo dynamic phenotypic
      alterations in response to changes in the cytokine milieu and in the composition
      of the extracellular matrix. Fibroblasts do not simply serve as matrix-producing
      cells, but may also regulate inflammation, modulate cardiomyocyte survival and
      function, mediate angiogenesis, and contribute to phagocytosis of dead cells.
      SUMMARY: In the injured myocardium, fibroblasts are derived predominantly from
      resident populations and serve a wide range of functions.

PMID- 29057166
TI  - Regulation of Exercise-Induced Autophagy in Skeletal Muscle.
AB  - PURPOSE OF REVIEW: Physical exercise is a highly effective method to prevent
      several pathogenic conditions, such as obesity, type 2 diabetes and
      cardiovascular diseases, largely due to metabolic adaptations induced by exercise
      in skeletal muscle. Yet how exercise induces the beneficial effects in muscle
      remains to be fully elucidated. Autophagy is a lysosomal degradation pathway that
      regulates nutrient recycling, energy production and organelle quality control.
      The autophagy pathway is upregulated in response to stress during exercise and
      muscle contraction, and may be an important mechanism mediating exercise-induced
      health benefits. RECENT FINDINGS: A number of studies have indicated that
      physical exercise induces non-selective autophagy and selective mitophagy in
      skeletal muscle in animal models and humans. The AMPK-ULK1 and the FoxO3
      signaling pathways play an essential role in the activation of the upstream
      autophagy machinery in skeletal muscle during exercise. The autophagy activity is
      required for health benefits of exercise, as in different autophagy-deficient
      mouse lines exercise-induced effects are abolished. SUMMARY: This review aims to
      summarize and highlight the most recent findings on the role of autophagy in
      muscle maintenance, the molecular pathways that upregulate autophagy during
      exercise, and the potential functions of exercise-induced autophagy and mitophagy
      in skeletal muscle.

PMID- 29057167
TI  - Pharmacogenetics in Cardiovascular Medicine.
AB  - PURPOSE OF REVIEW: Pharmacogenetics is an important component of precision
      medicine. Even within the genomic era, several challenges lie ahead in the road
      towards clinical implementation of pharmacogenetics in the clinic. This review
      will summarize the current state of knowledge regarding pharmacogenetics of
      cardiovascular drugs, focusing on those with the most evidence supporting
      clinical implementation- clopidogrel, warfarin and simvastatin. RECENT FINDINGS:
      There is limited translation of pharmacogenetics into clinical practice primarily
      due to the absence of outcomes data from prospective, randomized, genotype
      directed clinical trials. There are several ongoing randomized controlled trials
      that will provide some answers as to the clinical utility of genotype-directed
      strategies. Several academic medical centers have pushed towards clinical
      implementation where the clinical validity data are strong. Their experiences
      will inform operational requirements of a clinical pharmacogenetics testing
      including the timing of testing, incorporation of test results into the
      electronic health record, reimbursement and ethical issues. SUMMARY:
      Pharmacogenetics of clopidogrel, warfarin and simvastatin are three examples
      where pharmacogenetics testing may provide added clinical value. Continued
      accumulation of evidence surrounding clinical utility of pharmacogenetics markers
      is imperative as this will inform reimbursement policy and drive adoption of
      pharamcogenetics into routine care.

PMID- 29057168
TI  - Metabolic Dysregulation in Amyotrophic Lateral Sclerosis: Challenges and
      Opportunities.
AB  - PURPOSE OF REVIEW: Amyotrophic lateral sclerosis (ALS) is a progressive
      neurodegenerative disease for which there is no cure and treatments are at best
      palliative. Several genes have been linked to ALS, which highlight defects in
      multiple cellular processes including RNA processing, proteostasis and
      metabolism. Clinical observations have identified glucose intolerance and
      dyslipidemia as key features of ALS however the causes of these metabolic
      alterations remain elusive. RECENT FINDINGS: Recent studies reveal that motor
      neurons and muscle cells may undergo cell type specific metabolic changes that
      lead to utilization of alternate fuels. For example, ALS patients' muscles
      exhibit reduced glycolysis and increased reliance on fatty acids. In contrast,
      ALS motor neurons contain damaged mitochondria and exhibit impaired lipid beta
      oxidation, potentially leading to increased glycolysis as a compensatory
      mechanism. SUMMARY: These findings highlight the complexities of metabolic
      alterations in ALS and provide new opportunities for designing therapeutic
      strategies based on restoring cellular energetics.

PMID- 29057169
TI  - The Co-Development of Relational Aggression and Disruptive Behavior Symptoms from
      Late Childhood through Adolescence.
AB  - Researchers have debated whether relational aggression is a developmentally
      normative behavior or a sign of some underlying psychopathology. However, due to
      the dearth of longitudinal studies, we know little about how relational
      aggression and more severe forms of disruptive behavior co-develop. The present
      study examined bidirectional associations between relational aggression and two
      psychiatric disorders, Oppositional Defiant Disorder (ODD) and Conduct Disorder
      (CD), using data from a longitudinal study of 674 Mexican-origin youth followed
      from age 10 to 16. Results showed that individuals who engaged in relational
      aggression tended to increase over time in ODD and CD symptoms, and conversely,
      individuals exhibiting symptoms of ODD and CD tended to increase in relational
      aggression. These findings held for boys and girls, for youth born in Mexico and
      the U.S., and after controlling for physical aggression. Thus, relational
      aggression seems to be both a developmentally-normative behavior and a predictor
      of future mental health problems.

PMID- 29057170
TI  - Toward a Functional View of the P Factor in Psychopathology.
AB  - Evidence indicates the existence of a superordinate factor of general
      psychopathology, which has been termed p. Among the issues raised by this
      discovery is whether this factor has substantive meaning or not. This article
      suggests a functional interpretation of the p factor, based in part on a family
      of dual process models, in which an associative system and a deliberative system
      compete for influence over action. The associative system is frequently said to
      be impulsively responsive to emotions. We hypothesize that this impulsive
      responsivity to emotion underlies the p factor. One benefit of this view is to
      use the same underlying process variable to account for both internalizing and
      externalizing vulnerabilities, as well as aspects of thought disorder. Evidence
      is reviewed linking impulsive reactivity to emotion to the p factor, and
      (separately) to internalizing, externalizing, and thought-disorder symptoms.
      Alternative interpretations are considered.

PMID- 29057171
TI  - Elderly Cancer Survivors Reflect on Coping Strategies During the Cancer Journey.
AB  - PURPOSE: This paper focuses on perspectives of elderly cancer survivors on their
      experiences of coping with cancer during various phases of their illness journey,
      ranging from diagnosis phase to treatment and finally considering post treatment
      survivorship. Anchored in the stress paradigm, the purpose of this study was to
      explore the meaning of living with cancer and older adults' orientations to
      coping with stressors encountered during their cancer journey as reflected in
      narratives of elderly cancer survivors. METHODS: A nonclinical sample of 174
      older adults who reported a cancer diagnosis were selected from a panel study of
      successful aging. In-depth interviews with respondents focused on perceived
      stressors and coping strategies at different phases of their cancer experience.
      Themes were derived from narratives based on consensus by two raters. RESULTS:
      Most of the elderly patients accepted their diagnosis without dismay. Resolve and
      determination during the diagnosis phase was followed by assuming a more passive
      role during the treatment phase, relying on expert medical care. During the
      longer term survivorship phase older adults looked back at the adaptations they
      found most useful. The majority reported valuing active coping styles. These
      include seeking social support and instrumental orientations to dealing with the
      illness followed by religious or spiritual approaches. CONCLUSIONS: The "on time"
      interpretation of having a cancer diagnosis in old age may diminish the
      stressfulness of the diagnosis and may enhance the patients' ability to
      proactively deal with the reality of their illness.

PMID- 29057172
TI  - Cerebral and Retinal Neurovascular Changes: A Biomarker for Alzheimer's Disease.
AB  - OBJECTIVES: Biomarker quest for Alzheimer's disease (AD) has gone a long way by
      studying various anatomical, physiological and biochemical parameters for
      detecting disease onset and predicting prognosis. Almost all the studies converge
      on the single hypothesis of the amyloid and Tau pathway. Recently, vascular
      hypothesis has evolved drawing attention towards a complex dynamic anatomical and
      physiological entity, neuro-vascular (NV) unit. Pathological changes at this
      level, altering the normal physiology such as auto-regulation and dynamics of
      blood brain barrier have been hypothesized as a probable basis for AD. This paper
      attempts to review the existing data on the vascular hypothesis and the current
      trends in analyzing the NV unit in AD. DESIGN: This review initially focuses on
      the cerebral NV coupling followed by the retinal neurovascular coupling that
      mirrors the cerebral pathophysiology. The pathophysiology and the potential tools
      to diagnose AD at the level of NV unit are analyzed. Further, it examines the
      drawbacks in existing methods for analyzing the same. FINDINGS: None of the
      current studies have emphasized the importance of studying the complex dynamic NV
      unit as a whole. This review strongly recommends the combination of vascular and
      neuro-glial parameters using objective methods for estimating the physiological
      and pathological changes in the NV unit. DISCUSSION AND CONCLUSION: This review
      highlights the importance of retina for non-invasive estimation of the same.
      Also, novel algorithms for retinal image analysis have been proposed. The purpose
      of this review is to highlight the importance of retinal findings in
      neurodegenerative disorders and to create awareness among the
      neuroophthalmologists, of the potential benefits of ophthalmological tools in
      screening dementia patients.

PMID- 29057174
TI  - Concurrent Occurrence of Primary Biliary Cirrhosis and Rheumatoid Arthritis.
AB  - Primary biliary cirrhosis (PBC) is an autoimmune cholestatic disorder of the
      liver. A diagnostic serum marker for PBC is an anti-mitochondrial antibody. Most
      prominent histologic findings of PBC are portal inflammation and destruction of
      interlobular bile ducts. The PBC occurs only in 40 to 400 individuals per million
      in the general population. About 1.8 - 5.6% of individuals with this rare
      disorder have rheumatoid arthritis (RA). This case report describes a 56-year-old
      female with concurrent rheumatoid arthritis and primary biliary cirrhosis. The
      patients with RA are at higher risk of developing PBC compared to the general
      population. Thus, abnormal liver function test in the patients with RA,
      especially in the absence of alternative cause, warrants thorough investigation
      for PBC. Early diagnosis and treatment will improve the outcome of patients who
      develop PBC.

PMID- 29057173
TI  - Pathogenesis, diagnosis and therapeutic strategies in WHIM syndrome
      immunodeficiency.
AB  - 21 INTRODUCTION: WHIM syndrome is a rare combined primary immunodeficiency
      disorder caused by autosomal dominant gain-of-function mutations in the chemokine
      receptor CXCR4. It is the only Mendelian condition known to be caused by mutation
      of a chemokine or chemokine receptor. As such, it provides a scientific
      opportunity to understand chemokine-dependent immunoregulation in humans and a
      medical opportunity to develop mechanism-based treatment and cure strategies. 22
      AREAS COVERED: This review covers the clinical features, genetics,
      immunopathogenesis and clinical management of WHIM syndrome. Clinical trials of
      targeted therapeutic agents and potential cure strategies are also included. 23
      EXPERT OPINION: WHIM syndrome may be particularly amenable to mechanism-based
      therapeutics for three reasons: 1) CXCR4 has been validated as the molecular
      target in the disease by Mendelian genetics; 2) the biochemical abnormality is
      excessive CXCR4 signaling; and 3) antagonists selective for CXCR4 have been
      developed. Plerixafor is FDA-approved for hematopoietic stem cell (HSC)
      mobilization and has shown preliminary safety and efficacy in phase I clinical
      trials in WHIM syndrome. Gene editing may represent a viable cure strategy, since
      chromothriptic deletion of the disease allele in HSCs resulted in clinical cure
      of a patient and because CXCR4 haploinsufficiency enhances engraftment of
      transplanted HSCs in mice.

PMID- 29057175
TI  - Knowledge, Attitude and Practices Regarding Benign Testicular Disorders in the
      Educated Young Men of Pakistan.
AB  - Background It has been seen that despite the increasing incidence of benign
      testicular disorders (BTDs), little work has been done towards its awareness
      among the male populace. Also, the trend of not seeking help in this regard is
      concerning. In this study, we aim to better perceive the level of understanding
      and common practices regarding BTDs among educated young men. Methods A cross
      sectional study was carried out among two groups of ages 14-20 and 21-28 years.
      The inclusion criterion was that of educated males in an urban setting. Data were
      collected through a standardized questionnaire using cluster sampling by
      independent interviewers. The questionnaire consisted of four parts dealing with
      demographics, knowledge, attitudes and practices. Chi-square and Mann-Whitney U
      test were used as the primary statistical tests. Results The sample population
      consisted of an equal number of participants between the ages of 14 and 20, and
      between 21 and 28 years (n = 200, 50%). About half the participants (n = 215,
      53.8%) were not familiar with the term BTDs. The majority (n = 324, 78.8%) of
      participants were not aware of symptoms of BTDs. Three-fourth of the participants
      believed that the subject is considered taboo in Pakistan (n = 307, 73.6%) while
      a majority of participants (n = 340, 85%) believed media coverage can help spread
      awareness of BTDs. A huge number (n = 268, 67%) thought that BTDs can cause
      fertility problems while one-third of them would not perform testicular self
      examination (TSE) in case of pain or swelling in the scrotal region (n = 119,
      29.8). The level of education and age were significantly associated with the
      knowledge regarding symptoms and types of BTDs. Conclusion Knowledge of BTDs and
      practices of TSE in the young educated men of Karachi are alarmingly poor.
      Therefore, there is an urgent need to create awareness at all levels using
      different strategies and platforms.

PMID- 29057176
TI  - The Effect of Conversion from a Calcineurin Inhibitor to Sirolimus on Skin Cancer
      Reduction in Post-renal Transplantation Patients.
AB  - In kidney transplant patients, skin cancer is the most commonly involved
      neoplasm. More than 90% of post-transplantation skin cancers are nonmelanoma skin
      cancers (NMSCs). The majority of them are squamous cell carcinomas and basal cell
      carcinomas. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus are
      immunosuppressive agents given after solid organ transplantation, but they can
      also promote tumor growth. Sirolimus is a novel class of immunosuppressants and
      has been proven to have antineoplastic properties. We review clinical trials and
      meta-analyses studying if conversion from CNI to sirolimus in post-renal
      transplantation patients decreases the development of NMSCs. A critical appraisal
      of the literature demonstrated that, while smaller scale studies tended to yield
      no clinically significant data, larger clinical trials and meta-analyses
      supported the conclusion that converting to sirolimus in post-renal transplant
      patients leads to reductions in skin cancer development. As a result, we conclude
      that conversion to sirolimus likely reduces NMSC in post-renal transplantation
      patients. Larger scale clinical trials with more rigorous stratification and less
      patient dropout rate are needed for more definitive conclusions.

PMID- 29057177
TI  - A Rare Case Report of a Paratesticular Fibrous Pseudotumor Mimicking a Hydrocele.
AB  - Tumors arising in the spermatic cord are very rare. The common benign tumors of
      the spermatic cord include adenomatoid tumor, lipoma, neurofibroma, and
      leiomyoma. We report a rare case of fibrous pseudotumor of the spermatic cord
      presenting clinically as a hydrocele. A 28-year-old male presented with the
      complaint of swelling in the left scrotum, which gradually progressed in size
      over four years. Clinically, the swelling was soft and fluctuant. The left testis
      was not separately made out and a diagnosis of left hydrocele was made. On
      scrotal exploration, a large 12 x 7 cm fleshy mass was seen in the left
      hemiscrotum with the left testis adherent to the upper pole of the mass. The mass
      was dissected out from the testis, and the histology showed features of fibrous
      pseudotumor of the spermatic cord. Fibrous pseudotumor of the spermatic cord is a
      very rare entity and can pose a diagnostic challenge. Preoperative scrotal
      ultrasound and intraoperative frozen section assessment can prevent unnecessary
      orchiectomies in young patients with paratesticular fibrous pseudotumors.

PMID- 29057178
TI  - Salmonella Infection After Craniotomy.
AB  - Salmonella is an uncommon cause of meningitis, especially after neurosurgery.
      Here, we present a case of Salmonella meningitis after craniotomy, likely due to
      physical contact with a snake after surgery, with contiguous spread from the
      patient's hand to her wound. The purpose of this report is to serve as a reminder
      that patients undergoing neurosurgery should avoid contact with pets, including
      snakes and other reptiles, in the postoperative period and practice good hand
      hygiene.

PMID- 29057179
TI  - Chiari I Malformation and Spinal Cord Ischemia in a Cadaver.
AB  - With advanced imaging, the Chiari I malformation (CIM) is more frequently
      diagnosed than in the past when this entity was identified most commonly at
      autopsy. Herein, we report the rare case of an adult cadaver found not only to
      have CIM but also adjacent spinal cord ischemia. This case is discussed in the
      context of chronic compression of the spinal cord by a CIM and the need for close
      monitoring of these patients.

PMID- 29057181
TI  - Allopurinol-Induced Drug Reaction with Eosinophilia and Systemic Symptoms
      Syndrome: A Cause of Acalculous Cholecystitis?
AB  - Acalculous cholecystitis (AC) is an inflammation of the gallbladder in the
      absence of gallstones. There are many risk factors associated with AC. However,
      this report implicates allopurinol as an inciting agent for a severe systemic
      drug reaction, i.e., the drug reaction with eosinophilia and systemic symptoms
      (DRESS) syndrome complicated by AC. We report a Chinese woman who presented on
      two occasions with a diffuse maculopapular rash, elevated liver enzymes, and
      upper abdominal pain attributable to acute AC, the second episode of which
      developed after the reintroduction of allopurinol treatment for gout. The AC
      complicated the DRESS syndrome during the course of her hospitalization.

PMID- 29057180
TI  - Extensor Digitorum Brevis Manus: A Comprehensive Review of this Variant Muscle of
      the Dorsal Hand.
AB  - The extensor digitorum brevis manus (EDBM) is a variant muscle located on the
      dorsum of the hand. This variant of the fourth compartment has often eluded
      preoperative diagnosis and led to unnecessary repeat visits to the operating room
      owing to its lack of notoriety. As a result, we aim to review the literature
      concerning the EDBM with respect to its embryology, comparative anatomy and
      variants, and clinical significance in an attempt to increase awareness and help
      in preoperative diagnosis and management. A total of 21 articles were reviewed.
      The results show that the EDBM often goes underdiagnosed and is frequently
      discovered incidentally in the operating room or in cadaveric dissections. There
      are multiple variations of the EDBM that, in certain instances, dictate the
      correct method of management. While there has been a reversal of opinions on
      which technique is the most popular at relieving symptoms caused by the EDBM,
      current arguments stand for retinacular release only when the EDBM serves as a
      sole extensor for one of the indices. In other instances where this is not the
      case, surgical excision of the EDBM proved to be the most effective at relieving
      symptoms.

PMID- 29057182
TI  - Anterior Inferior Cerebellar Arteries Juxtaposed with the Internal Acoustic
      Meatus and Their Relationship to the Cranial Nerve VII/VIII Complex.
AB  - Vascular loops in the cerebellopontine angle (CPA) and their relationship to
      cranial nerves have been used to explain neurological symptoms. The anterior
      inferior cerebellar artery (AICA) has variable branches producing vascular loops
      that can compress the facial cranial nerve (CN) VII and vestibulocochlear (CN
      VIII) nerves. AICA compression of the facial-vestibulocochlear nerve complex can
      lead to various clinical presentations, including hemifacial spasm (HFS),
      tinnitus, and hemiataxia. The formation of arterial loops inside or outside of
      the internal auditory meatus (IAM) can cause abutment or compression of CN VII
      and CN VIII. Twenty-five (50 sides) fresh adult cadavers underwent dissection of
      the cerebellopontine angle in the supine position. In regard to relationships
      between the AICA and the nerves of the facial/vestibulocochlear complex, 33
      arteries (66%) traveled in a plane between the facial/nervus intermedius nerves
      and the cochlear and vestibular nerves. Five arteries (10%) traveled below the CN
      VII/VIII complex, six (12%) traveled posterior to the nerve complex, four (8%)
      formed a semi-circle around the upper half of the nerve complex, and two (4%)
      traveled between and partially separated the nervus intermedius and facial nerve
      proper. Our study found that the majority of AICA will travel in a plane between
      the facial/nervus intermedius nerves and the cochlear and vestibular nerves.
      Although the relationship between the AICA and porus acusticus and AICA and the
      nerves of the CN VII/VIII complex are variable, based on our findings, some
      themes exist. Surgeons should consider these with approaches to the
      cerebellopontine angle.

PMID- 29057184
TI  - A Giant Adrenal Mass in a Super Obese Patient.
AB  - Giant pheochromocytomas (Pheo) are rare entities requiring clinical suspicion
      coupled with strategic diagnostic evaluation to confirm the diagnosis. The
      majority of cases are discovered incidentally. The diagnosis consists of
      biochemical evaluation and imaging study to localize the mass. Pathological
      examination confirms the diagnosis. The female patient in this case report
      presented with chest pain, palpitation of three weeks duration and was found on
      evaluation to have an abdominal mass concerning for pheochromocytoma. She was
      treated with surgical resection. The pheo measured 20.5 x 18 x 10 cm and weighed
      2,582 grams. Pathological examination confirmed the diagnosis of
      pheochromocytoma.

PMID- 29057183
TI  - A Low-Cost, Low-Skill Model for Efficient Breast Cancer Screening in Low Resource
      Rural Settings of a Developing Country.
AB  - Objective To suggest a low-cost, easily-operable, non-invasive imaging modality
      for cancer detection in rural settings. Method A total of 212 cases with palpable
      breast masses aged 18 - 65 years were enrolled and underwent thorough clinical,
      mammographic, and ultrasonographic (USG) evaluation. Imaging findings were
      reported using the American College of Radiology (ACR) Breast Imaging Reporting
      and Data System (BI-RADS(r)) criteria. The findings were confirmed
      histopathologically. Data were analyzed using the Chi-square test. Results The
      malignancy rate was 35.8% (n = 76). On mammography, lesions size, margins, shape,
      calcification, and distorted arch/skin thickening were significantly associated
      with malignancy. On USG, the number of nodules, shape, margins, echotexture,
      posterior wall echo, through transmission changes, distorted arch/skin
      thickening, microlobulation, duct extension, and height/width ratio were
      significantly associated with malignancy. Independently, mammography and USG had
      a sensitivity of 78.1% and 80.3%, respectively, and a specificity of 83.3% and
      89.0%, respectively. Using a positive result of either study as the criteria, the
      sensitivity was 97.4% and the specificity was 80.1%. Conclusion The combined use
      of mammography and USG provides high sensitivity and specificity, thus showing
      that a combination of two can be used as a screening tool for use in low resource
      rural settings.

PMID- 29057185
TI  - Combination of Pyridoxine and Thiamine Treatment in Bilateral Induced Ptosis in a
      Child: Case Report and Review of Literature.
AB  - Ptosis is a rare side effect of vincristine chemotherapy in patients treated for
      cancer. We report a case of a child with common B-cell acute lymphoblastic
      leukemia who developed bilateral moderate ptosis following the chemotherapy
      protocol of the United Kingdom Acute Lymphoblastic Leukemia (ALL) regimen A. The
      patient showed dramatic clinical improvement after a combination of oral
      pyridoxine and thiamine treatment. We provide a literature review of this
      uncommon presentation.

PMID- 29057186
TI  - Traumatic Pancreatitis: A Rare Complication of Cardiopulmonary Resuscitation.
AB  - An elderly gentleman was successfully revived after undergoing cardiopulmonary
      resuscitation (CPR) for cardiac arrest. Post CPR, the patient developed acute
      pancreatitis which was likely complication of inappropriately delivered chest
      compressions which caused further complications and resulted in the death of the
      patient. This case underlines the importance of quality chest compressions that
      includes correct placement of hands by the operator giving chest compressions to
      avoid lethal injuries to the receiver.

PMID- 29057187
TI  - Modelling and Manufacturing of a 3D Printed Trachea for Cricothyroidotomy
      Simulation.
AB  - Cricothyroidotomy is a life-saving medical procedure that allows for tracheal
      intubation. Most current cricothyroidotomy simulation models are either expensive
      or not anatomically accurate and provide the learner with an unrealistic
      simulation experience. The goal of this project is to improve current simulation
      techniques by utilizing rapid prototyping using 3D printing technology and expert
      opinions to develop inexpensive and anatomically accurate trachea simulators. In
      doing so, emergency cricothyroidotomy simulation can be made accessible,
      accurate, cost-effective and reproducible. Three-dimensional modelling software
      was used in conjunction with a desktop three-dimensional (3D) printer to design
      and manufacture an anatomically accurate model of the cartilage within the
      trachea (thyroid cartilage, cricoid cartilage, and the tracheal rings). The
      initial design was based on dimensions found in studies of tracheal anatomical
      configuration. This ensured that the landmarking necessary for emergency
      cricothyroidotomies was designed appropriately. Several revisions of the original
      model were made based on informal opinion from medical professionals to establish
      appropriate anatomical accuracy of the model for use in rural/remote
      cricothyroidotomy simulation. Using an entry-level desktop 3D printer, a low cost
      tracheal model was successfully designed that can be printed in less than three
      hours for only $1.70 Canadian dollars (CAD). Due to its anatomical accuracy,
      flexibility and durability, this model is great for use in emergency medicine
      simulation training. Additionally, the model can be assembled in conjunction with
      a membrane to simulate tracheal ligaments. Skin has been simulated as well to
      enhance the realism of the model. The result is an accurate simulation that will
      provide users with an anatomically correct model to practice important skills
      used in emergency airway surgery, specifically landmarking, incision and
      intubation. This design is a novel and easy to manufacture and reproduce, high
      fidelity trachea model that can be used by educators with limited resources.

PMID- 29057188
TI  - Pineal Gland Tumor but not Pinealoma: A Case Report.
AB  - The pineal gland is a small pinecone-shaped and functionally endocrine structure
      located in the epithalamus region. Developmentally, the pineal gland is
      considered as a part of the epithalamus. It plays a role in the entrainment of
      the circadian rhythms of an organism by producing melatonin, a functionally
      important hormone. Lesions of the pineal region are rare compared to other parts
      of the brain. A lesion may be tumorous or non-tumorous in nature. The most common
      lesions are tumors that are pineal parenchymal tumors (PPT) in origin. Gliomas
      are the second most common tumors in the pineal region. We report a case of a
      high-grade oligodendroglioma, not commonly seen in the pineal region, in a 45
      year-old male. The patient was suspected to have a mass in the pineal region on a
      computed tomography (CT) scan and histology confirmed the diagnosis of
      oligodendroglioma. This is a unique case because only five such cases have been
      reported so far.

PMID- 29057189
TI  - Prevalence of Vitamin B12 Deficiency in Patients with Type II Diabetes Mellitus
      on Metformin: A Study from Khyber Pakhtunkhwa.
AB  - Background Metformin is the most common oral hypoglycemic used and associated
      with certain abnormalities. The objective was to evaluate and define the
      occurrence and bases of vitamin B12 deficiency amongst patients on Metformin for
      diabetes mellitus type II. Methods A cross-sectional study was conducted on 209
      patients having diabetes type II between January-December 2016. The patients aged
      > 45 years and who had taken metformin for at least three months were recruited
      with regular follow-up at the Endocrinology Unit of Hayatabad Medical Complex and
      Diabetic Center Hayatabad, Peshawar. The patients were included in a survey after
      which they had their serum B12 levels measured. Serum B12 levels < 150 pg/ml is
      defined as the B12 deficiency. Results About 29.66% of diabetic patients had
      confirmed the B12 insufficiency through laboratory tests. The patients on
      metformin had statistically lower values of B12 (P = 0.01). For the patients who
      smoked, vitamin B12 deficiency was significantly higher than those who did not
      smoke (p= <0.001). Also in patients using multivitamins, vitamin B12 deficiency
      was lower compared to nonusers (p=0.05). Conclusion Our study shows that for the
      patients with type 2 diabetes (T2DM), long-term treatment with metformin and
      smoking are associated with higher chances of developing vitamin B12 deficiency.
      Clinicians should, therefore, recognize this significant element and should
      screen diabetics who are on metformin treatment for any B12 insufficiency, which
      may be hidden, especially patients coming with neurologic symptoms. Additionally,
      multi vitamins taken daily may have a protective role.

PMID- 29057190
TI  - A Call for Emergency Action: Telepsychiatry for Trauma Treatment Among Syrian
      Refugees.
AB  - The war in Syria has entered the seventh year, with no sign of resolution. It is
      often referred as "the greatest human tragedy" since World War 2. Because of
      limited health facilities, we propose telepsychiatric interventions for the
      provision of mental healthcare services in Syria and in refugee camps to treat
      post-trauma patients.

PMID- 29057191
TI  - Small-Town America's Despair: Infected Substance Users Needing Outpatient
      Parenteral Therapy and Risk Stratification.
AB  - Background  An active intravenous substance use disorder is often the primary
      cause of infectious diseases in this population of users and creates a barrier to
      successful parenteral antimicrobial management. The dilemma is compounded by
      dramatically limited resources in small US towns. Methods This retrospective
      review from January 2014 through July 2016 aimed to develop a risk stratification
      approach to aid rural healthcare providers in determining who among patients with
      addictive disorders could safely be discharged for outpatient antimicrobial
      therapy with a peripherally inserted central catheter (PICC). Results The high
      risk group had a greater likelihood of noncompliance with antimicrobial therapy
      completion, as well as subsequent illicit drug use during that time frame,
      compared with the moderate- and low-risk groups. The low-risk group and most of
      the moderate-risk group could be safely discharged into the community with PICC
      lines. Conclusions Key in the risk stratification proposal was identifying risk
      behaviors and determining their degree. Such information provides pivotal
      delineators in developing risk stratification criteria.

PMID- 29057192
TI  - Palliative Care Options for a Young Adult Patient with a Diffuse Intrinsic
      Pontine Glioma.
AB  - Diffuse intrinsic pontine gliomas (DIPGs) are rare but devastating brain tumors
      that occur primarily in children. These gliomas have poor prognoses and present
      options focus on palliation of symptoms and prolongation of life. Here, we
      present a case of a 16-year-old female diagnosed with a DIPG whose age group has
      been mostly left out of discussions regarding psychosocial support options. This
      report is meant to start a conversation about the different support options
      available at our institution that have shown promising results in the literature
      for palliative care applications. These options can include camps for patients
      with brain tumors, psychological counseling, the Ronald McDonald House, and other
      psychosocial programs. Many of these programs can be tailored to meet the
      specific needs of adolescent and young adult (AYA) patients and will hopefully be
      integrated into a comprehensive palliative care regimen in future studies.

PMID- 29057193
TI  - Long QT Syndrome Unveiled by a Fatal Combination of Medications and Electrolyte
      Abnormalities.
AB  - Long QT syndrome (LQTS) can present with syncope and seizure-like activity in the
      setting of torsades de pointes (TdP) with hemodynamic instability. Electrolyte
      abnormalities and medications can predispose to TdP in the setting of latent
      LQTS. An implantable cardioverter defibrillator (ICD) is needed if patients with
      TdP continue to be symptomatic despite medical treatment. We report a case of a
      patient who presented with seizures and was found to have prolonged corrected QT
      interval (QTc). During her admission, she was treated with ondansetron. She went
      into torsades de pointes and continued to have prolonged QTc. She underwent
      implantable cardioverter defibrillator (ICD) placement and remains asymptomatic
      to date.

PMID- 29057194
TI  - The dependence of the strength and thickness of field-aligned currents on solar
      wind and ionospheric parameters.
AB  - Sheared plasma flows at the low-latitude boundary layer (LLBL) correlate well
      with early afternoon auroral arcs and upward field-aligned currents. We present a
      simple analytic model that relates solar wind and ionospheric parameters to the
      strength and thickness of field-aligned currents (Lambda) in a region of sheared
      velocity, such as the LLBL. We compare the predictions of the model with DMSP
      observations and find remarkably good scaling of the upward region 1 currents
      with solar wind and ionospheric parameters in region located at the boundary
      layer or open field lines at 1100-1700 magnetic local time. We demonstrate that
      [Formula: see text] and Lambda ~ L when Lambda/L < 5 where L is the auroral
      electrostatic scale length. The sheared boundary layer thickness (Delta m ) is
      inferred to be around 3000 km, which appears to have weak dependence on Vsw. J||
      has dependencies on Delta m , Sigma p , nsw, and Vsw. The analytic model provides
      a simple way to organize data and to infer boundary layer structures from
      ionospheric data.

PMID- 29057195
TI  - Movement rehabilitation in virtual reality from then to now: how are we doing?
AB  - During the past decade, there has been a continuous exploration of how virtual
      environments can be used to facilitate motor recovery and relearning after
      neurological impairment. There are two goals for using virtual environments: to
      improve patients' rehabilitation outcomes beyond our current capabilities or to
      supplement labor-intensive and time consuming therapies with technology-based
      interventions. After over a decade of investigation, it seems appropriate to
      determine whether we are succeeding in meeting such goals.

PMID- 29057196
TI  - Robotic/virtual reality intervention program individualized to meet the specific
      sensorimotor impairments of an individual patient: a case study.
AB  - A majority of studies examining repetitive task practice facilitated by robots
      for the treatment of upper extremity paresis utilize standardized protocols
      applied to large groups. This study will describe a virtually simulated, robot
      based intervention customized to match the goals and clinical presentation of a
      gentleman with upper extremity hemiparesis secondary to stroke. MP, the subject
      of this case, is an 85-year-old man with left hemiparesis secondary to an
      intracerebral hemorrhage 5 years prior to examination. Outcomes were measured
      before and after a 1-month period of home therapy and after a 1-month virtually
      simulated, robotic intervention. The intervention was designed to address
      specific impairments identified during his PT examination. When necessary,
      activities were modified based on MP's response to his first week of treatment.
      MP's home training program produced a 3-s decline in Wolf Motor Function Test
      (WMFT) time and a 5-s improvement in Jebsen Test of Hand Function (JTHF) time. He
      demonstrated an additional 35-s improvement in JTHF and an additional 44-s
      improvement in WMFT subsequent to the robotic training intervention. A 24-h
      activity measurement and the Hand and Activities of Daily Living scales of the
      Stroke Impact Scale improved following the robotic intervention. Based on his
      responses to training we feel that we have established that a customized program
      of virtually simulated, robotically facilitated rehabilitation was feasible and
      resulted in larger improvements than an intensive home training program in
      several measurements of upper extremity function in our patient with chronic
      hemiparesis.

PMID- 29057197
TI  - Semi-Parametric Estimation and Inference for the Mean Outcome of the Single Time
      Point Intervention in a Causally Connected Population.
AB  - We study the framework for semi-parametric estimation and statistical inference
      for the sample average treatment-specific mean effects in observational settings
      where data are collected on a single network of connected units (e.g., in the
      presence of interference or spillover). Despite recent advances, many of the
      current statistical methods rely on estimation techniques that assume a
      particular parametric model for the outcome, even though some of the most
      important statistical assumptions required by these models are most likely
      violated in the observational network settings, often resulting in invalid and
      anti-conservative statistical inference. In this manuscript, we rely on the
      recent methodological advances for the targeted maximum likelihood estimation
      (TMLE) of causal effects in a network of causally connected units, to describe an
      estimation approach that permits for more realistic classes of data-generative
      models and provides valid statistical inference in the context of network
      dependent data. The approach is applied to an observational setting with a single
      time point stochastic intervention. We start by assuming that the true observed
      data-generating distribution belongs to a large class of semi-parametric
      statistical models. We then impose some restrictions on the possible set of the
      data-generative distributions that may belong to our statistical model. For
      example, we assume that the dependence among units can be fully described by the
      known network, and that the dependence on other units can be summarized via some
      known (but otherwise arbitrary) summary measures. We show that under our modeling
      assumptions, our estimand is equivalent to an estimand in a hypothetical iid data
      distribution, where the latter distribution is a function of the observed network
      data-generating distribution. With this key insight in mind, we show that the
      TMLE for our estimand in dependent network data can be described as a certain iid
      data TMLE algorithm, also resulting in a new simplified approach to conducting
      statistical inference. We demonstrate the validity of our approach in a network
      simulation study. We also extend prior work on dependent-data TMLE towards
      estimation of novel causal parameters, e.g., the unit-specific direct treatment
      effects under interference and the effects of interventions that modify the
      initial network structure.

PMID- 29057198
TI  - Longitudinal Studies on the Etiology of Cannabis Use Disorder: A Review.
AB  - PURPOSE OF REVIEW: This review summarizes the literature to date that has
      capitalized on the longitudinal research study framework in order to elucidate
      the etiology of cannabis use disorders (CUDs). RECENT FINDINGS: The studies are
      mixed with respect to reliable predictors of CUD development. Of the studies
      outlined, the most consistently indicated risk factors for CUD development
      include: male sex, past cannabis and other substance use (especially tobacco),
      and the presence of pre/comorbid psychopathology (especially mood disorders).
      Social motives and peer involvement may also play a role in this transition. Many
      of these CUD risk factors appear to be distinct from other factors linked with
      overall cannabis use. SUMMARY: CUD development is likely the product of
      interactions between biological, psychological, social, and environmental
      factors. However, many more well-planned and developmentally sensitive
      prospective studies are needed to identify specific and reliable risk factors for
      CUD development.

PMID- 29057199
TI  - Neural Correlates of Social Influence Among Cannabis Users.
AB  - PURPOSE OF REVIEW: Although peer influence is an important factor in the
      initiation and maintenance of cannabis use, few studies have investigated the
      neural correlates of peer influence among cannabis users. The current review
      summarizes research on the neuroscience of social influence in cannabis users,
      with the goal of highlighting gaps in the literature and the need for future
      research. RECENT FINDINGS: Brain regions underlying peer influence may function
      differently in cannabis users. Compared to non-using controls, regions of the
      brain underlying reward, such as the striatum, show greater connectivity with
      frontal regions, and also show hyperactivity when participants are presented with
      peer information. Other subcortical regions, such as the insula, show
      hypoactivation during social exclusion in cannabis users, indicating that neural
      responses to peer interactions may be altered in cannabis users. SUMMARY:
      Although neuroscience is increasingly being used to study social behavior, few
      studies have specifically focused on cannabis use, and therefore it is difficult
      to draw conclusions about social mechanisms that may differentiate cannabis users
      and controls. This area of research may be a promising avenue in which to explore
      a critical factor underlying cannabis use and addiction.

PMID- 29057200
TI  - Cannabis Withdrawal: A Review of Neurobiological Mechanisms and Sex Differences.
AB  - PURPOSE OF REVIEW: This report provides an updated overview of pre-clinical and
      clinical research on the etiology and biological substrates of the cannabis
      withdrawal syndrome. RECENT FINDINGS: Long-term cannabis use is associated with
      downregulation of type-1 cannabinoid receptors (CB1). Reduced CB1 receptor
      density is related to increased withdrawal during early abstinence, and the
      reduction in CB1 receptor density reverses with extended abstinence. Females have
      been shown to have increased rate and severity of a subset of cannabis withdrawal
      symptoms compared with men. SUMMARY: Recent studies have extended knowledge of
      the biological processes and individual difference variables that influence
      cannabis withdrawal. However, caveats include small sample sizes in clinical
      studies, participant samples that are predominantly male, and limited
      examinations of endocannabinoids, enzymes that degrade endocannabinoids, negative
      allosteric modulators, and other neurobiological systems that may directly impact
      cannabis withdrawal symptom expression.

PMID- 29057201
TI  - "Essentially, All Models are Wrong, but Some Are Useful": A Preliminary
      Conceptual Model Of Co-Occurring E-Cig and Alcohol Use.
AB  - PURPOSE OF REVIEW: As prevalence rates of electronic cigarette (e-cig) use
      increase, researchers and clinicians should not only be paying careful attention
      to the direct health effects of e-cigs, but also the potential impact e-cigs may
      have on alcohol use behaviors. We review the current state of the literature and
      propose a conceptual model for the relationship between e-cig and alcohol use,
      including important consequences, mechanisms, and moderators of this
      relationship. RECENT FINDINGS: The model is based in emerging literature
      examining the direct relationship between e-cig and alcohol use, as well as
      indirect evidence concerning potential mechanisms from research on cigarette and
      alcohol use. Overall, research indicates a robust relationship between e-cig and
      alcohol use. SUMMARY: We suggest that a relationship between e-cig use and
      alcohol use could be particularly problematic, especially for adolescents and for
      those with or at risk for alcohol use disorders. We hope the presented conceptual
      model can stimulate research in this area. We make research recommendations,
      including the need for more methodological rigor, including improved measurement
      of e-cig use, and expanding research to longitudinal and experimental designs.

PMID- 29057202
TI  - Autoimmune Reactivity in Graft Injury: Player or Bystander?
AB  - Organ transplantation is the only viable treatment for several end-stage organ
      failures. However chronic rejection prevents long-term graft survival.
      Traditionally this rejection was attributed to the development of alloimmunity in
      transplant patients. However recent evidence suggests that autoimmunity plays a
      larger role in chronic rejection of certain organ transplants, than alloimmunity.
      In this review we will focus on the history of autoimmunity in solid-organ
      transplantation and at look the Collagen Type V, K-alpha-tubulin, Vimentin,
      Cardiac myosin and Heat Shock Proteins as classical examples of auto-antigens in
      organ transplantation. We will also look at some of the recent reports looking at
      the mechanisms of autoimmunity and try to provide answers to some of the age-old
      questions in autoimmunity.

PMID- 29057203
TI  - Nanotechnological Approaches to Immunosuppression and Tolerance Induction.
AB  - PURPOSE OF REVIEW: Several preclinical studies have engineered nanoparticles for
      immune regulation, and have shown promising results in the fields of autoimmunity
      and cancer. In solid organ transplantation, the use of nanoparticle-based immune
      regulation has only just begun to emerge but holds significant promise for the
      improvement of our current standard of care immunosuppressive regimens. In this
      review, we will shed light on the current status of nanoparticle-engineered
      immunotherapeutics, and the potential application of these technologies to the
      field of organ transplantation. Further we discuss different strategies for
      delivery and potential cellular targeting moieties that could be utilized to
      obviate the need for high dose systemic immunosuppressive regimens. RECENT
      FINDINGS: Recent studies have shown the potential of immunosuppressive laden
      nanoparticles to increase bioavailability, drug release, and specifically target
      immune cell compartments as methods to provide recipient immunosuppressive
      sparing strategies. SUMMARY: Nanoparticle centered immunosuppressive strategies
      hold the potential to usher in a new era in transplant recipient management and
      could hold the key to minimizing off-target effects of immunosuppressants, along
      with prolonging transplant survival.

PMID- 29057204
TI  - Shift Work: Disrupted Circadian Rhythms and Sleep-Implications for Health and
      Well-Being.
AB  - PURPOSE OF REVIEW: Our 24/7 society is dependent on shift work, despite mounting
      evidence for negative health outcomes from sleep displacement due to shift work.
      This paper reviews short- and long-term health consequences of sleep displacement
      and circadian misalignment due to shift work. RECENT FINDINGS: We focus on four
      broad health domains: metabolic health; risk of cancer; cardiovascular health;
      and mental health. Circadian misalignment affects these domains by inducing sleep
      deficiency, sympathovagal and hormonal imbalance, inflammation, impaired glucose
      metabolism, and dysregulated cell cycles. This leads to a range of medical
      conditions, including obesity, metabolic syndrome, type II diabetes,
      gastrointestinal dysfunction, compromised immune function, cardiovascular
      disease, excessive sleepiness, mood and social disorders, and increased cancer
      risk. SUMMARY: Interactions of biological disturbances with behavioral and
      societal factors shape the effects of shift work on health and well-being.
      Research is needed to better understand the underlying mechanisms and drive the
      development of countermeasures.

PMID- 29057205
TI  - microRNAs and connexins in bone: interaction and mechanisms of delivery.
AB  - PURPOSE OF REVIEW: To describe the current knowledge on the cross-talk between
      connexins and microRNAs (miRs) in bone cells. RECENT FINDINGS: Connexins play a
      crucial role on bone development and maintenance, and disruptions in their
      abundance or localization can affect how bone perceives and responds to
      mechanical, hormonal, and pharmacological stimuli. Connexin expression can be
      modified by miRs, which modulate connexin mRNA and protein levels. Recently,
      different manners by which miRs and connexins can interact in bone have been
      identified, including mechanisms that mediate miR exchange between cells in
      direct contact through gap junctions, or between distant cells via extracellular
      vesicles (EVs). SUMMARY: We bring to light the relationship between miRs and
      connexins in bone tissue, with special focus on regulatory effects of miRs and
      connexins on gene expression, as well as the mechanisms that mediate miR exchange
      between cells in direct contact through gap junctions, or between distant cells
      via EVs.

PMID- 29057206
TI  - Control of the Osteoblast Lineage by Mitogen-Activated Protein Kinase Signaling.
AB  - PURPOSE OF THE REVIEW: This review will provide a timely assessment of MAP kinase
      actions in bone development and homeostasis with particular emphasis on
      transcriptional control of the osteoblast lineage. RECENT FINDINGS: ERK and p38
      MAP kinases function as transducers of signals initiated by the extracellular
      matrix, mechanical loading, TGF-beta, BMPs and FGF2. MAPK signals may also affect
      and/or interact with other important pathways such as WNT and HIPPO. ERK and p38
      MAP kinase pathways phosphorylate specific osteogenic transcription factors
      including RUNX2, Osterix, ATF4 and DLX5. For RUNX2, phosphorylation at specific
      serine residues initiates epigenetic changes in chromatin necessary for
      decondensation and increased transcription. MAPK also suppresses marrow
      adipogenesis by phosphorylating and inhibiting PPARgamma, which may explain the
      well-known relationship between reduced skeletal loading and marrow fat
      accumulation. SUMMARY: MAPKs transduce signals from the extracellular environment
      to the nucleus allowing bone cells to respond to changes in hormonal/growth
      factor signaling and mechanical loading thereby optimizing bone structure to meet
      physiological and mechanical needs of the body.

PMID- 29057208
TI  - The Efficacy of Neoadjuvant Chemotherapy for HER-2-Positive Locally Advanced
      Breast Cancer and Survival Analysis.
AB  - To provide reference data, we retrospectively investigated the effects of
      neoadjuvant chemotherapy (NAC) on 119 patients with HER-2+ locally advanced
      breast cancer, treated from November 2010 to July 2016, with respect to
      influencing factors and survival. They were divided into the pathological
      complete response (pCR; n = 15; 12.6%) and non-pCR (n = 104; 87.4%) groups. We
      used Chi2 and logistic tests to the analyze effect and influencing factors.
      Survival rate was analyzed by the Kaplan-Meier method and Log-rank test. We lost
      12 patients (including 1 pCR patient) and followed 107 patients, of whom 31 (all
      in the non-pCR group) had local recurrences or distant metastasis. The two groups
      significantly differed in 3-year disease-free survival (pCR group: 100%; non-pCR
      group: 59.0%; P = 0.039); pCR was significantly affected by histological grade,
      PR status, Ki67 index, primary tumor size, clinical staging, and number of
      trastuzumab cycles. The model was tested, and the difference was statistically
      significant (Chi2 = 31.938, P = 0.032). Patients with HER-2+ locally advanced
      breast cancer with pCR responses to NAC have improved prognoses. Patients without
      pCR have increased risk for relapse. The use of a combination of NAC, such as
      trastuzumab and chemotherapy, and more cycles should be considered to increase
      the likelihood of pCR.

PMID- 29057207
TI  - Harnessing Epicardial Progenitor Cells and Their Derivatives for Rescue and
      Repair of Cardiac Tissue After Myocardial Infarction.
AB  - PURPOSE OF REVIEW: Ischemic heart disease and stroke lead to the greatest number
      of deaths worldwide. Despite decreased time to intervention and improvements in
      the standard of care, 1 out of 5 patients that survive a myocardial infarction
      (MI) still face long-term chronic heart failure and a 5-year mortality rate of
      about 50%. Based on their multi-potency for differentiation and paracrine
      activity, epicardial cells and their derivatives have potential to rescue
      jeopardized tissue and/or promote cardiac regeneration. Here we review the
      diagnosis and treatment of MI, basic epicardial cell biology, and potential
      treatment strategies designed to harness the reparative properties of epicardial
      cells. RECENT FINDINGS: During cardiac development, epicardial cells covering the
      surface of the heart generate migratory progenitor cells that contribute to the
      coronary vasculature and the interstitial fibroblasts. Epicardial cells also
      produce paracrine signals required for myocardial expansion and cardiac growth.
      In adults with myocardial infarction, epicardial cells and their derivatives
      provide paracrine factors that affect myocardial remodeling and repair. At
      present, the intrinsic mechanisms and extrinsic signals that regulate epicardial
      cell fate and paracrine activity in adults remain poorly understood. SUMMARY:
      Human diseases that result in heart failure due to negative remodeling or
      extensive loss of viable cardiac tissue require new, effective treatments.
      Improved understanding of epicardial cell function(s) and epicardial-mediated
      secretion of growth factors, cytokines and hormones during cardiac growth,
      homeostasis and injury may lead to new ways to treat patients with myocardial
      infarction.

PMID- 29057209
TI  - Obesity anthropometric indicators associated with cardiometabolic risk in
      Portuguese children and adolescents.
AB  - The purpose of this study was to determine the association between
      cardiometabolic risk with body mass index and skinfold independently or in
      combination in youth. This cross-sectional study comprised a convenience sample
      of 450 children and adolescents (255 girls), aged 10 to 18 years old. Indicators
      of body composition were measured, and hemodynamic assessment completed. The
      association between body mass index and/or sum of skinfolds and cardiometabolic
      risk (z score of the sum of triglycerides/high density lipoprotein cholesterol,
      waist circumference, and mean blood pressure), was calculated using Generalized
      Linear Models Regression. The results showed that youngsters classified as
      overweight or obese with the highest skinfold measurements had the strongest
      association with cardiometabolic risk (< beta >: 2.60; IC 95%: 2.25-3.0) when
      compared with those exhibiting normal skinfold thickness (< beta >: 1.78; IC 95%:
      1.30-2.20). Body mass index was most strongly associated with cardiometabolic
      risk (< beta >: 1.78; IC 95%: 1.3-2.2), in comparison to skinfold thickness,
      which was associated to a lesser extent (< beta >: 0.41; IC 95%: 0.34-0.49).
      Results of this cross-sectional study indicate that body mass index is more
      strongly associated with cardiometabolic risk than skinfold thickness. However
      when these two measures of overweight/obesity are combined, prediction of
      cardiometabolic risk is further improved. It is therefore important that public
      health professionals consider both body mass index and sum of skinfolds to better
      predict cardiometabolic risk in overweight and obese youth. Implications for
      future research include the use of longitudinal designs and inclusion of children
      from other racial/ethnic groups.

PMID- 29057211
TI  - Relative relationships of general shame and body shame with body dysmorphic
      phenomenology and psychosocial outcomes.
AB  - Body Dysmorphic Disorder (BDD) is characterized by a preoccupation with a
      perceived flaw in appearance and repetitive avoidance behaviors. BDD involves
      severe psychosocial outcomes (e.g., depression, suicidality, functional
      impairment). Identifying correlates of BDD symptoms and outcomes can inform
      treatment. Shame, a painful emotion felt in response to critical self-judgment,
      may be one key correlate. However, research on shame in BDD is scarce and
      previous studies have not distinguished general shame from body shame. This study
      examines the relative relationships between body shame and general shame with
      body dysmorphic phenomenology and psychosocial outcomes. Participants (N = 184)
      were recruited online via BDD organizations and completed a survey. Path analysis
      was used to examine associations between body and general shame with 1) body
      dysmorphic phenomenology and 2) depression severity, suicide risk, and functional
      impairment. Both types of shame were differentially related to outcomes. Body
      shame was more strongly related to phenomenology, whereas general shame was more
      strongly related to psychosocial outcomes. Thus, it may be important for BDD
      treatment to focus on reducing both general and body shame. Further research
      should evaluate whether current treatments adequately address and reduce general
      and body shame, and whether addressing shame promotes better treatment outcomes.

PMID- 29057210
TI  - Latinos with obsessive-compulsive disorder: Mental healthcare utilization and
      inclusion in clinical trials.
AB  - Previous research has documented that ethnic minorities, particularly Latinos,
      obtain fewer mental health services than Caucasians (Kearney, Draper, & Baron
      2005; Sue, Fujino, Hu, Takeuchi, & Zane, 1991). Conceivably, this may be due to a
      wide array of cultural issues (e.g., negative stigma attached to mental health,
      and language, socio-economic, and acculturation barriers), symptom disparities
      across Caucasian and Latino groups, or lack of effective outreach methods by
      clinicians and researchers. However, research is limited. As a result, Latinos
      may be insufficiently represented in clinical studies for OCD, making it unclear
      whether evidence-based treatments demonstrate the same efficacy and effectiveness
      for Latinos as has been demonstrated for Caucasians. The current study takes an
      in-depth analysis of 98 efficacy and effectiveness studies for OCD from across
      the Western hemisphere and reports the rates of Latino inclusion from each
      sample. Ninety clinical studies in the US and Canada, as well as eight clinical
      studies in Mexico and Central America were reviewed. Findings showed that only 11
      (24%) US and Canadian studies included Latino participants, illustrating an
      overwhelming underrepresentation of Latinos in clinical studies for OCD. Further
      explanation of the results and their implications are discussed, along with
      suggestions for effectively improving access to mental health research and
      appropriate treatments.

PMID- 29057212
TI  - Examining psychological inflexibility as a transdiagnostic process across
      psychological disorders.
AB  - The current cross-sectional study examined psychological inflexibility, a process
      in which behavior is rigidly guided by psychological reactions rather than direct
      contingencies or personal values, as a transdiagnostic process relevant to a
      range of depressive, anxiety, substance use and eating disorders. A sample of 972
      first-year college students between 17 and 20 years of age completed self-report
      measures of psychological inflexibility and psychological distress as well as a
      structured diagnostic interview. Psychological inflexibility was significantly
      higher across a range of current and lifetime depressive and anxiety disorders as
      well as lifetime history of eating disorders, relative to students with no
      disorder, even after controlling for general psychological distress. Findings
      were mixed for substance use disorders, with a more consistent pattern for
      lifetime history than for current disorders. Psychological inflexibility was also
      related to having comorbid depressive, anxiety, and substance use disorders
      relative to only having one of these diagnoses. Results are discussed in relation
      to research on psychological inflexibility as a transdiagnostic pathological
      process and target for interventions.

PMID- 29057213
TI  - Posttraumatic stress disorder symptoms and hypercoagulability during emergency
      department evaluation for acute coronary syndrome.

PMID- 29057214
TI  - The alpha-Tubulin gene TUBA1A in Brain Development: A Key Ingredient in the
      Neuronal Isotype Blend.
AB  - Microtubules are dynamic cytoskeletal polymers that mediate numerous, essential
      functions such as axon and dendrite growth and neuron migration throughout brain
      development. In recent years, sequencing has revealed dominant mutations that
      disrupt the tubulin protein building blocks of microtubules. These tubulin
      mutations lead to a spectrum of devastating brain malformations, complex
      neurological and physical phenotypes, and even fatality. The most common tubulin
      gene mutated is the alpha-tubulin gene TUBA1A, which is the most prevalent alpha
      tubulin gene expressed in post-mitotic neurons. The normal role of TUBA1A during
      neuronal maturation, and how mutations alter its function to produce the
      phenotypes observed in patients, remains unclear. This review synthesizes current
      knowledge of TUBA1A function and expression during brain development, and the
      brain malformations caused by mutations in TUBA1A.

PMID- 29057216
TI  - Contribution of in Vivo Experimental Challenges to Understanding Flat Oyster
      Ostrea edulis Resistance to Bonamia ostreae.
AB  - Bonamiosis due to the parasite Bonamia ostreae has been associated with massive
      mortality outbreaks in European flat oyster stocks in Europe. As eradication and
      treatment are not possible, the control of the disease mainly relies on transfer
      restriction. Moreover, selection has been applied to produce resistant flat
      oyster families, which present better survival and lower prevalence than non
      selected oysters. In order to better understand the mechanisms involved in
      resistance to bonamiosis, cellular and molecular responses of 2 oyster groups
      (selected oysters and wild-type oysters) were analyzed in the context of
      experimental injection and cohabitation infections. Cellular responses including
      non-specific esterases detection, ROS production and phagocytosis activity were
      analyzed by flow cytometry. Four genes homologous to those shown to be involved
      in immunity were selected (Inhibitor of apotosis OeIAP, Fas ligand OeFas-ligand,
      Oe-SOD, and OeEc-SOD) and monitored by quantitative reverse-transcription PCR
      (qRT-PCR). Infected oysters showed higher phagocytosis activity than controls.
      Infected selected oyster show a lower phagocytosis activity which might be a
      protection against the parasite infection. The expression of OeIAP and OeFas
      ligand gene was significantly increased in selected oysters at 5 days post
      injection. OeIAP gene expression appeared to be significantly increased in wild
      type oysters at 8 days post-injection. Our results suggest that resistance to
      bonamiosis partly relies on the ability of the oysters to modulate apoptosis.

PMID- 29057215
TI  - Targeted Therapy for Medullary Thyroid Cancer: A Review.
AB  - Medullary thyroid cancers (MTCs) constitute between 2 and 5% of all thyroid
      cancers. The 10-year overall survival (OS) rate of patients with localized
      disease is around 95% while that of patients with regional stage disease is about
      75%. Only 20% of patients with distant metastases at diagnosis survive 10 years
      which is significantly lower than for differentiated thyroid cancers. Cases with
      regional metastases at presentation have high recurrence rates. Adjuvant external
      radiation confers local control but not improved OS. The management of residual,
      recurrent, or metastatic disease till a few years ago was re-surgery with local
      measures such as radiation. Chemotherapy was used with marginal benefit. The
      development of targeted therapy has brought in a major advantage in management of
      such patients. Two drugs-vandetanib and cabozantinib-have been approved for use
      in progressive or metastatic MTC. In addition, several drugs acting on other
      steps of the molecular pathway are being investigated with promising results.
      Targeted radionuclide therapy also provides an effective treatment option with
      good quality of life. This review covers the rationale of targeted therapy for
      MTC, present treatment options, drugs and methods under investigation, as well as
      an outline of the adverse effects and their management.

PMID- 29057217
TI  - Characterization and Distribution of the autB Gene in Neisseria meningitidis.
AB  - We aimed to investigate and understand the characterization and distribution of
      the autB gene in Neisseria meningitidis in China. autB is flanked by two
      conservative genes, smpB and glcD, and it can be present in the majority of
      meningococcal isolates, but not in 053442 of clonal complex 4821 (CC4821) which
      contains a 968 bp sequence. In this study, we sequenced the intervenient region
      between smpB and glcD in 178 Chinese N. meningitidis strains isolated from both
      patients and carriers. There were 110 serogroupable strains, other 68 were non
      groupable (NG). Ninety nine of the 178 strains were clustered into 13 CCs, the
      remaining 79 were unassigned (UA). CC4821 is one of the dominant CCs in China.
      Forty of the 42 CC4821 strains and 26 of the 79 UA strains were autB-null, while
      the remaining 12 CCs were autB-positive. According to the N-terminal sequence,
      most (97/112) of the autB-positive strains were clustered into AutB1 and the
      remaining 15 were AutB2. The autB gene and its flanking intergenic sequences was
      superseded by a perfectly conservative sequence of an identical 968 bp in all of
      the autB-null N. meningitidis strains which had no identity with the relatively
      conservative intergenic sequences that flanked the autB gene in autB-positive
      strains. There was a 10 bp DNA uptake sequence (DUS) at the beginning of the
      interval 968 bp sequence in the autB-null strains while there was a 9 bp
      Haemophilus-specific uptake sequence (hUS) at the beginning of the partial holB
      gene and at the end of the partial tmk gene in autB-positive strains, holB and
      tmk gene were flanking the autB gene in Haemophilus. In conclusion, not all
      pathogenic N. meningitidis strains especially CC4821 possess the autB gene in
      China and the corresponding spacer region of the autB-null strains was not
      homologous to that found in autB-positive strains. There's a hypothesis that the
      DUS and hUS are likely to play a key part in the mechanism of uptake or loss of
      the autB gene.

PMID- 29057218
TI  - Differences between completely physically inactive and low active older men and
      their response to an exercise intervention: the Veterans LIFE study.
AB  - BACKGROUND: Physical activity interventions typically do not report behavioral
      changes in activity sub-groups. The aim of this study was to compare baseline
      differences and changes in physical activity between truly physically inactive
      men and low active men enrolled in a twelve-month, home-based physical activity
      intervention. METHODS: Veterans with a mean age of 77.6 years were randomized to
      either a physical activity intervention or usual care. Measures included self
      reported physical activity, physical function, and physical performance. RESULTS:
      At baseline, the physically inactive group reported more symptoms and poorer
      functioning than the low active group. At 12 months, physically inactive men
      randomized to the intervention group increased their physical activity to an
      average of 73.3 minutes per week. Physically inactive individuals randomized to
      the control group were eight times more likely to remain inactive compared to the
      low active group. CONCLUSIONS: Completely physically inactive older men can
      markedly increase physical activity levels with a long-term intervention. Without
      such intervention, the likelihood of this group remaining inactive is eightfold.

PMID- 29057219
TI  - Transcranial stimulation over the left inferior frontal gyrus increases false
      alarms in an associative memory task in older adults.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is a potential tool
      for alleviating various forms of cognitive decline, including memory loss, in
      older adults. However, past effects of tDCS on cognitive ability have been mixed.
      One important potential moderator of tDCS effects is the baseline level of
      cognitive performance. METHODS: We tested the effects of tDCS on face-name
      associative memory in older adults, who suffer from performance deficits in this
      task relative to younger adults. Stimulation was applied to the left inferior
      prefrontal cortex during encoding of face-name pairs, and memory was assessed
      with both a recognition and recall task. RESULTS: Face-name memory performance
      was decreased with the use of tDCS. This result was driven by increased false
      alarms when recognizing rearranged face-name pairs. CONCLUSIONS: This result
      suggests that tDCS can lead to increased false alarm rates in recognition memory,
      and that effects of tDCS on a specific cognitive task may depend upon cognitive
      capability for that task.

PMID- 29057220
TI  - Iatrogenic Dysnatremias in Children with Acute Gastroenteritis in High-Income
      Countries: A Systematic Review.
AB  - BACKGROUND: Acute gastroenteritis (AGE) causing dehydration with or without
      dysnatremias is a common childhood health challenge. While it is accepted that
      oral rehydration therapy is preferred, clinical factors or parent and healthcare
      provider preferences may lead to intravenous rehydration (IVR). Isotonic
      solutions are increasingly recommended in most scenarios requiring IVR.
      Nevertheless, children with AGE, having ongoing losses of water and electrolytes,
      represent a unique population. OBJECTIVES: To evaluate the association between
      acquired dysnatremias and IVR in children with AGE. METHODS: A systematic search
      of MEDLINE database was conducted through September 14, 2016. Observational
      studies and clinical trials conducted in high-income countries were included. The
      Grades of Recommendation, Assessment, Development, and Evaluation approach was
      used to evaluate the overall quality of evidence for each outcome. RESULTS: 603
      papers were identified of which 6 were included (3 randomized controlled trials
      and 3 observational studies). Pooling of patient data was not possible due to
      significantly different interventions or exposures. Single studies results
      demonstrated that within 24 h, administration of isotonic saline was not
      associated with a significant decline in serum sodium while hypotonic solutions
      (0.2-0.45% saline) were associated, in one study, with mean serum sodium declines
      from 1.3 mEq/L (139.2, SD 2.9-137.9, SD 2.5) in 133 young infants (aged 1-28
      months), to 5.7 (SD 3.1) mEq/L in a subgroup of 18 older children (age mean 5.8,
      SD 2.7 years). Both isotonic and hypotonic saline were shown to be associated
      with improvement of baseline hyponatremia in different studies. Baseline
      hypernatremia was corrected within 4-24 h in 81/83 (99.6%) children using
      hypotonic saline IVR. CONCLUSION: There is a paucity of publications assessing
      the risk for acquired dysnatremias associated with IVR in children with AGE.
      Current high-quality evidence suggests that, short-term use of isotonic solutions
      is safe and effective in most children with AGE; hypotonic solutions may also be
      appropriate in some subpopulations, however, the quality of available evidence is
      low to very low. Further research investigating outcomes associated with IVR use
      beyond 24 h focusing on specific age groups is required.

PMID- 29057221
TI  - Investigation of Summer Learning Loss in the UK-Implications for Holiday Club
      Provision.
AB  - This study sought to examine whether summer learning loss occurs in spelling and
      word reading in a population of 77 primary school aged children aged between 5
      and 10 years (37 boys, mean age 100 months, SD 18 months, and 40 girls mean age
      103 months, SD 16 months) attending three schools in areas of low socioeconomic
      status in Scotland and the North East of England. Word reading and spelling was
      measured using the word reading and spelling subtests of the Wide Ranging
      Achievement Test. Participants were tested on three occassions: immediately
      before and immediately after a 7-week summer break, and again after 7-weeks of
      teaching. The results showed a significant main effect of time for spelling
      scores, F(2,136) = 21.60, p < 0.001, [Formula: see text]. Post-hoc analysis
      [t(73) = 4.84, p <= 0.001] showed that spelling scores were significantly higher
      at the end of the summer term (M = 26.57) than at the start of the new academic
      year (M = 25.38). Likewise, spelling scores after 7 weeks post return to school
      (M = 27.61) were significantly higher than at the start of the Autumn term, t(73)
      = 7.79, p <= 0.001. Performance in spelling declined when children returned to
      school immediately after the summer holiday (M = 25.38) but 7 weeks later,
      performance had improved beyond the baseline reported immediately before the
      summer break (M = 26.57) [t(73) = 4.40, p <= 0.001]. There was also a main effect
      of school in relation to spelling scores, [F(2,68) = 6.49, p < 0.05, [Formula:
      see text]], with children from school 2 and school 3 outperforming children from
      school 1. There was no signficant main effect of gender [F(1,68) = 1.47, p >
      0.05, [Formula: see text]]. None of the interactions were significant. There was
      no main effect of time on word reading scores [F(2,136) = 1.12, p >= 0.05,
      [Formula: see text]]. However, there was a main effect of school [F(2,68) = 4.85,
      p <= 0.01, [Formula: see text]] in relation to reading scores, with children from
      school 2 and school 3 outperforming children from school 1. There was no
      significant main effect of gender [F(1,68) = 0.37, p >= 0.05, [Formula: see
      text]]. None of the interactions were significant. This is the first such study
      in the UK to demonstrate that after a summer break of seven weeks, summer
      learning loss occurred, or at least stagnation in learning, in a population of
      primary school aged children attending schools in areas of low SES in relation to
      spelling. However, after seven weeks of teaching, children caught up to and
      exceeded the level achieved in spelling prior to the summer break. However, the
      summer holiday period did not result in a loss of word reading skill, reading
      scores were consistent across the entire study.

PMID- 29057222
TI  - Identification of Trombospondin-1 as a Novel Amelogenin Interactor by Functional
      Proteomics.
AB  - Amelogenins are a set of low molecular-weight enamel proteins belonging to a
      group of extracellular matrix (ECM) proteins with a key role in tooth enamel
      development and in other regeneration processes, such as wound healing and
      angiogenesis. Since only few data are actually available to unravel amelogenin
      mechanism of action in chronic skin healing restoration, we moved to the full
      characterization of the human amelogenin isoform 2 interactome in the secretome
      and lysate of Human Umbilical Vein Endothelial cells (HUVEC), using a functional
      proteomic approach. Trombospondin-1 has been identified as a novel and
      interesting partner of human amelogenin isoform 2 and their direct binding has
      been validated thought biophysical orthogonal approaches.

PMID- 29057223
TI  - Complete Genome Sequence and Comparative Analysis of Staphylococcus condimenti
      DSM 11674, a Potential Starter Culture Isolated from Soy Sauce Mash.

PMID- 29057224
TI  - Commentary: Atrial Fibrillation Dynamics and Ionic Block Effects in Six
      Heterogeneous Human 3D Virtual Atria with Distinct Repolarization Dynamics.

PMID- 29057225
TI  - Pathogenic Effector Th2 Cells in Allergic Eosinophilic Inflammatory Disease.
AB  - There is an absolute requirement for Th2 cells in the pathogenesis of allergen
      driven eosinophil-rich type 2 inflammation. Although Th2 cells are generally
      regarded as a homogeneous population, in the past decade there has been
      increasing evidence for a minority subpopulation of IL-5+ Th2 cells that have
      enhanced effector function. This IL-5+ Th2 subpopulation has been termed
      pathogenic effector Th2 (peTh2), as it exhibits greater effector function and
      disease association than conventional Th2 cells. peTh2 cells have a different
      expression profile, differentially express transcription factors, and
      preferentially use specific signaling pathways. As such, peTh2 cells are a
      potential target in the treatment of allergic eosinophilic inflammation. This
      review examines peTh2 cells, both in mouse models and human disease, with an
      emphasis on their role in the pathogenesis of allergic eosinophilic inflammation.

PMID- 29057226
TI  - Holm Oak (Quercus ilex) Transcriptome. De novo Sequencing and Assembly Analysis.

PMID- 29057228
TI  - The Potential for Big Data in Animal Disease Surveillance in Ireland.

PMID- 29057227
TI  - Getting Old through the Blood: Circulating Molecules in Aging and Senescence of
      Cardiovascular Regenerative Cells.
AB  - Global aging is a hallmark of our century. The natural multifactorial process
      resulting in aging involves structural and functional changes, affecting
      molecules, cells, and tissues. As the western population is getting older, we are
      witnessing an increase in the burden of cardiovascular events, some of which are
      known to be directly linked to cellular senescence and dysfunction. In this
      review, we will focus on the description of a few circulating molecules, which
      have been correlated to life span, aging, and cardiovascular homeostasis. We will
      review the current literature concerning the circulating levels and related
      signaling pathways of selected proteins (insulin-like growth factor 1, growth and
      differentiation factor-11, and PAI-1) and microRNAs of interest (miR-34a, miR
      146a, miR-21), whose bloodstream levels have been associated to aging in
      different organisms. In particular, we will also discuss their potential role in
      the biology and senescence of cardiovascular regenerative cell types, such as
      endothelial progenitor cells, mesenchymal stromal cells, and cardiac progenitor
      cells.

PMID- 29057229
TI  - Phase mask-based multimodal superresolution microscopy.
AB  - We demonstrate a multimodal superresolution microscopy technique based on a phase
      masked excitation beam in combination with spatially filtered detection. The
      theoretical foundation for calculating the focus from a non-paraxial beam with an
      arbitrary azimuthally symmetric phase mask is presented for linear and two-photon
      excitation processes as well as the theoretical resolution limitations.
      Experimentally this technique is demonstrated using two-photon luminescence from
      80 nm gold particle as well as two-photon fluorescence lifetime imaging of
      fluorescent polystyrene beads. Finally to illustrate the versatility of this
      technique we acquire two-photon fluorescence lifetime, two-photon luminescence,
      and second harmonic images of a mixture of fluorescent molecules and 80 nm gold
      particles with > 120 nm resolution (lambda/7). Since this approach exclusively
      relies on engineering the excitation and collection volumes, it is suitable for a
      wide range of scanning-based microscopies.

PMID- 29057230
TI  - Emerging uses of biomarkers in lung cancer management.

PMID- 29057231
TI  - Prioritizing molecular markers to test for in the initial workup of advanced non
      small cell lung cancer: wants versus needs.
AB  - The current standard of care for molecular marker testing in patients with
      advanced non-small cell lung cancer (NSCLC) has been evolving over several years
      and is a product of the quality of the evidence supporting a targeted therapy for
      a specific molecular marker, the pre-test probability of that marker in the
      population, and the magnitude of benefit seen with that treatment. Among the
      markers that have one or more matched targeted therapies, only a few are in the
      subset for which they should be considered as most clearly worthy of prioritizing
      to detect in the first line setting in order to have them supplant other first
      line alternatives, and in only a subset of patients, as defined currently by
      NSCLC histology. Specifically, this currently includes testing for an activating
      epidermal growth factor receptor (EGFR) mutation or an anaplastic lymphoma kinase
      (ALK) or ROS1 rearrangement. This article reviews the history and data supporting
      the prioritization of these markers in patients with non-squamous NSCLC, a
      histologically selected population in whom the probability of these markers
      combined with the anticipated efficacy of targeted therapies against them is high
      enough to favor these treatments in the first line setting. In reviewing the
      evidence supporting this very limited core subset of most valuable molecular
      markers to detect in the initial workup of such patients, we can also see the
      criteria by which other actionable markers need to reach in order to be widely
      recognized as reliably valuable enough to warrant prioritization to detect in the
      initial workup of advanced NSCLC as well.

PMID- 29057232
TI  - Expanded molecular interrogation for potential actionable targets in non-squamous
      non-small cell lung cancer.
AB  - The advent of targeted therapies has established new standards of care for
      defined molecular subsets of non-small cell lung cancer (NSCLC). Not only has
      this led to significant changes in the routine clinical management of lung cancer
      e.g., multiplexed genomic testing, but it has provided important principles and
      benchmarks for determining "actionability". At present, the clinical paradigms
      are most evolved for EGFR mutations and ALK rearrangements, where multiple
      randomized phase III trials have determined optimal treatment strategies in both
      treatment naive and resistant settings. However, this may not always be feasible
      with low prevalence alterations e.g., ROS1 and BRAF mutations. Another emerging
      observation is that not all targets are equally "actionable", necessitating a
      rigorous preclinical, clinical and translational framework to prosecute new
      targets and drug candidates. In this review, we will cover the role of targeted
      therapies for NSCLC harbouring BRAF, MET, HER2 and RET alterations, all of which
      have shown promise in non-squamous non-small cell lung cancer (ns-NSCLC). We
      further review some early epigenetic targets in NSCLC, an area of emerging
      interest. With increased molecular segmentation of lung cancer, we discuss the
      upcoming challenges in drug development and implementation of precision oncology
      approaches, especially in light of the complex and rapidly evolving therapeutic
      landscape.

PMID- 29057233
TI  - Relevance of genetic alterations in squamous and small cell lung cancer.
AB  - The precision medicine revolution has led to the development and US FDA approval
      of multiple targeted therapies in non-squamous non-small cell lung cancers,
      including tyrosine kinase inhibitors targeting EGFR, ALK, and ROS1. However, the
      development of targeted therapies for squamous cell lung cancers (SQCLCs) and
      small cell lung cancers (SCLCs) has lagged behind and the mainstay of systemic
      therapy for most patients with metastatic disease remains chemotherapy; which has
      seen little meaningful progress over the past three decades. The ideal of
      precision medicine in these diseases may appear elusive; however, recent
      comprehensive genomic analysis of SQCLC and SCLC has led to multiple
      breakthroughs in our understanding of the biology of these diseases and has led
      to new therapeutic approaches currently under active clinical investigation. This
      review will focus on the therapeutic relevance of these alterations in their
      respective diseases and new insights into promising therapeutics currently under
      investigation.

PMID- 29057234
TI  - Prognostic and predictive biomarkers post curative intent therapy.
AB  - Large-scale screening trials have demonstrated that early diagnosis of lung
      cancer results in a significant reduction in lung cancer mortality. Despite
      improvements in detecting more lung cancers at early stages, the 5-year survival
      rates of lung cancers diagnosed before widespread disease is only 30-50%. High
      rates of recurrence, despite early diagnosis, suggest the need to improve
      treatment strategies based on the likelihood of recurrence in patient subsets, as
      well as explore the role of predictive markers for therapy selection in the
      adjuvant setting. In the era of personalized medicine, there have been a wide
      array of molecular alterations and signatures studied for their potential
      prognostic and predictive utility, however most have failed to translate into
      clinical tools. This review will discuss progress made in clinical management of
      lung cancer, and recent progress in the development of patient selection tools
      for the refinement of early stage lung cancers.

PMID- 29057235
TI  - PD-L1 as a biomarker in NSCLC: challenges and future directions.

PMID- 29057236
TI  - Beyond PD-L1 testing-emerging biomarkers for immunotherapy in non-small cell lung
      cancer.
AB  - Recently, a firmer understanding of tumor immunology and tumor escape mechanisms
      has led to the development of immune checkpoint inhibitors, antibodies against
      programmed death-1 (PD-1) and its ligand (PD-L1). Nivolumab, pembrolizumab, and
      atezolizumab have dramatically altered the treatment paradigm in non-small cell
      lung cancer (NSCLC) and have each demonstrated improvements in outcomes and
      quality of life when compared to chemotherapy. Enrichment strategies to better
      select those patients more likely to respond have identified PD-L1 staining by
      immunohistochemistry (IHC) to be a predictive biomarker in both treatment naive
      and refractory patients. Unfortunately, many challenges exist with this strategy
      and underscore the need for further exploration for more reliable biomarkers.
      Multiple tissue and plasma-based enrichment strategies have been identified in
      the hope of identifying patients more likely to benefit from checkpoint
      inhibitors. These include tumor mutational load; the "inflamed phenotype"
      including tumor infiltrating lymphocytes (TILS) and immunoscore; T-cell receptor
      clonality; gene signatures, and several plasma biomarkers. Several studies have
      revealed many of these biomarkers to be reliable predictors of response to immune
      checkpoint inhibitors across multiple tumor types. Given the small nature of
      these studies, additional prospective studies are warranted to formalize and
      validate each of these enrichment strategies.

PMID- 29057237
TI  - Emerging uses of biomarkers in lung cancer management: molecular mechanisms of
      resistance.
AB  - Management of patients with advanced non-small cell lung cancer (NSCLC) has
      recently been transformed by molecularly targeted and immunotherapeutic agents.
      In patients with EGFR/ALK/ROS mutated NSCLC, first line molecular therapy is the
      standard of care. Moreover, immune checkpoint inhibitors are revolutionary
      treatment options for advanced NSCLC and are now the standard of care in front
      line or later line settings. Both classes of agents have led to improved patient
      outcomes, however, primary resistance and development of acquired resistance to
      both targeted and immunotherapeutic agents is commonly observed, limiting the use
      of these agents in clinical settings. In this review, we will discuss the most
      recent advances in understanding the mechanisms of primary and acquired
      resistance, progress in the spectrum of assays detecting causative molecular
      events and the development of new generations of inhibitors to overcome acquired
      resistance.

PMID- 29057238
TI  - Non-invasive diagnostic platforms in management of non-small cell lung cancer:
      opportunities and challenges.
AB  - Several non-invasive diagnostic platforms are already being incorporated in
      routine clinical practice in the work up and monitoring of patients with lung
      cancer. These approaches have great potential to improve patient selection and
      monitor patients while on therapy, however several challenges exist in clinical
      validation and standardization of such platforms. In this review, we summarize
      the current technologies available for non-invasive diagnostic evaluation from
      the blood of patients with non-small cell lung cancer (NSCLC), and discuss the
      technical and logistical challenges associated incorporating such testing in
      clinical practice.

PMID- 29057239
TI  - Circulating DNA in EGFR-mutated lung cancer.
AB  - Circulating tumor DNA (ctDNA) consists of short double stranded DNA fragments
      that are released by tumors including non-small cell lung cancer (NSCLC). With
      the identification of driver mutations in the epidermal growth factor receptor
      (EGFR) gene and development of targeted tyrosine kinase inhibitors (TKIs), the
      clinical outcome of NSCLC patients in this subgroup has improved tremendously.
      The gold standard to assess EGFR mutation is through tissue biopsy, which can be
      limited by difficulty in accessing the tumor, inability of patients to tolerate
      invasive procedures, insufficient sample for molecular testing and inability to
      capture intratumoral heterogeneity. The great need for rapid and accurate
      identification of activating EGFR mutations in NSCLC patients paves the road for
      ctDNA technology. Studies have demonstrated ctDNA to be a reliable complement to
      tumor genotyping. Platforms like digital polymerase chain reaction (PCR) and next
      generation sequencing based analyses have made it possible to identify EGFR
      mutations in plasma with high sensitivity and specificity. This article will
      provide an overview on ctDNA in the context of EGFR mutated NSCLC, especially its
      emerging applications in diagnosis, disease surveillance, treatment monitoring
      and detection of resistance mechanisms.

PMID- 29057241
TI  - Erratum to epigenetics of colorectal cancer: emerging circulating diagnostic and
      prognostic biomarkers.
AB  - [This corrects the article DOI: 10.21037/atm.2017.04.45.].

PMID- 29057242
TI  - Retraction to cardiotoxicity of cancer chemotherapy: identification, prevention
      and treatment.
AB  - [This retracts the article DOI: 10.21037/atm.2017.06.35.].

PMID- 29057240
TI  - Emerging uses of circulating tumor DNA in advanced stage non-small cell lung
      cancer.
AB  - Targeted therapies have dramatically changed the treatment paradigm for a select
      group of patients with non-small cell lung cancer (NSCLC) whose tumors harbor
      targetable genetic aberrations. Patients with such genetic changes enjoy
      excellent responses to tyrosine kinase inhibitors (TKIs), but resistance is
      nearly inevitable. Resistance to first line TKIs is heterogeneous and
      multifactorial-multiple resistance mechanisms have been reported, and different
      metastatic foci in the same patient may have distinct resistance mechanisms. The
      recent approval of next-generation TKIs specific to particular resistance
      mechanisms, and the likely future approval of others, necessitates the
      acquisition of repeat molecular analysis at time of progression. Tumor tissue has
      traditionally been the preferred source to detect oncogenic driver and resistance
      mutations, but tissue biopsies are invasive and often difficult to obtain. The
      use of circulating tumor DNA (ctDNA), so-called "liquid biopsies", has emerged as
      a promising technique to molecularly profile tumors non-invasively and is
      becoming increasingly utilized in the routine management of lung cancer. This
      review will describe the current role of ctDNA in the management of lung cancer,
      and explore emerging data that point towards its increasingly important role in
      clinical care.

PMID- 29057244
TI  - PDGFA regulation of dermal adipocyte stem cells.

PMID- 29057243
TI  - Smoking, depression, and hospital costs of respiratory cancers: Examining race
      and sex variation.
AB  - OBJECTIVE: The role of smoking and depression relative to hospital cost for lung
      cancer (LC) remains unknown. METHODS: We extracted data on depression, smoking
      history, demographics, and hospital charges on patients with respiratory cancers
      (ICD-9 codes 161-163,165) from the 2008 Tennessee Hospital Discharge Data System.
      The sample (n=6,665) was mostly white (86%) and male (57). Age-adjusted rates
      were developed per CDC methodology, and hospital costs were compared for LC with
      vs. without depression and smoking. RESULTS: Three findings (p<.001) emerged: (i)
      LC rate was higher among blacks than whites, and higher among males than females;
      (ii) While 66% of LC smoked (more males than females without racial variation),
      24% had depression (more females and whites were depressed); (iii) The LC
      hospital cost was 54% higher compared to non-LC, and this cost doubled for LC
      with depression and smoking vs. those without such characteristics. CONCLUSION:
      While LC is more prevalent among blacks and males, depression is higher among
      female and white patients. Since depression with higher costs existed among LC
      patients, our findings point to: (i) possibility of cost savings by diagnosing
      and treating depression among LC, and (ii) implementing proven smoking cessation
      programs to reduce LC morbidity and hospital costs.

PMID- 29057245
TI  - A case report of congenital glycogen storage liver cirrhosis treated with bone
      marrow derived stem cells.
AB  - Liver cirrhosis represents a state of end-stage failure that is usually fatal.
      The condition results in liver dysfunction, recurrent ascites, encephalopathy,
      renal failure, splenomegaly, bleeding, and a poor quality of life in general.
      With the current severe shortage of donated organs, the only available treatment
      in the developing countries remains palliative care. We report a case of
      congenital metabolic liver cirrhosis due to glycogen storage disease diagnosed at
      age eight. The patient, a male, received bone marrow derived mononuclear cells
      (BMMC) at age 16 and again at age 17 with significant improvement of his
      biochemical liver function tests, ascites build-up, asthenia, splenomegaly and
      quality of life. Furthermore, liver biopsies showed clear reduction of the
      inflammation and fibrosis from Ishak score dropped from 3 to 1 paralleling the
      symptomatic improvement of the patient.

PMID- 29057246
TI  - Engineering of extracellular vesicles as drug delivery vehicles.
AB  - Extracellular vesicles (EVs) are secreted membrane-enclosed nano-sized particles
      (40-1,000 nm) that deliver biological information between cells. The molecular
      composition of these subcellular particles includes growth factor receptors,
      ligands adhesion proteins, mRNA, miRNAs, lncRNA and lipids that are derived from
      donor cells. A number of studies demonstrated that stem cell-derived EVs are the
      key mediator of tissue repair and regeneration in multiple animal disease models.
      In addition, the composition of these particles is known to be altered in cancer
      and disease pathology suggesting them for useful in diagnostic and therapeutic
      purposes. Their endogenous origin and biological properties offer benefits over
      conventional drug delivery systems (DDS), such as liposome, synthetic
      nanoparticles and prompted the further application of EVs as drug delivery
      vehicles for chemical drugs, genetic materials and proteins. The contents of EVs
      can be efficiently modified by chemical, biological or physical means. Thus, EVs
      can be an innovative DDS as it can overcome physical and biological barriers and
      safely deliver therapeutic drugs to target tissues. In this minireview, we
      summarized current progress on the strategies of drug loading onto EVs; ex vivo
      and in vivo loading.

PMID- 29057248
TI  - Cell lineage specification at single cell resolution.

PMID- 29057247
TI  - Extracellular vesicles as regulators of tumor fate: crosstalk among cancer stem
      cells, tumor cells and mesenchymal stem cells.
AB  - The tumor microenvironment comprises a heterogeneous population of tumorigenic
      and non-tumorigenic cells. Cancer stem cells (CSCs) and mesenchymal stem cells
      (MSCs) are components of this microenvironment and have been described as key
      regulators of different aspects of tumor physiology. They act differently on the
      tumor: CSCs are described as tumor initiators and are associated with tumor
      growth, drug resistance and metastasis; MSCs can integrate the tumor
      microenvironment after recruitment and interact with cancer cells to promote
      tumor modifications. Extracellular vesicles (EVs) have emerged as an important
      mechanism of cell communication under the physiological and pathological
      conditions. In cancer, secretion of EVs seems to be one of the main mechanisms by
      which stem cells interact with other tumor and non-tumor cells. The transfer of
      bioactive molecules (lipids, proteins and RNAs) compartmentalized into EVs
      triggers different responses in the target cells, regulating several processes in
      the tumor as angiogenesis, tumor invasiveness and immune escape. This review
      focuses on the role of CSCs and MSCs in modulating the tumor microenvironment
      through secretion of EVs, addressing different aspects of the multidirectional
      interactions among stem cells, tumor and tumor-associated cells.

PMID- 29057249
TI  - Indoleamine 2,3-dioxygenase and survivin peptide vaccine combined with
      temozolomide in metastatic melanoma.
AB  - BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) and survivin have been identified
      as potential targets for cancer vaccination. In this phase II study a vaccine
      using the peptides Sur1M2 and IDO5 was combined with the chemotherapy
      temozolomide (TMZ) for treatment of metastatic melanoma patients. The aim was to
      simultaneously target several immune inhibiting mechanisms and the highly
      malignant cells expressing survivin. METHODS: HLA-A2 positive patients with
      advanced malignant melanoma were treated biweekly with 150 mg/m2 TMZ daily for 7
      days followed by subcutaneous vaccination with 250 ug of each peptide in 500 uL
      Montanide solution at day 8. Granulocyte-macrophage colony-stimulating factor was
      used as an adjuvant and topical imiquimod was applied prior to vaccination.
      Treatment was continued until disease progression. Clinical response was
      evaluated by PET-CT and immunological outcome was assessed by ELISPOT and flow
      cytometry. RESULTS: In total, 17 patients were treated with a clinical benefit
      rate of 18% including one patient with partial tumor regression. Immune analyses
      revealed a vaccine specific response in 8 (67%) of 12 patients tested, a
      significant decrease in the frequency of CD4+ T-cells during treatment, a
      tendency towards decreasing frequencies of naive CD4+ and CD8+ T-cells, and
      increasing frequencies of memory CD4+ and CD8+ T-cells. CONCLUSIONS: These
      results demonstrate that vaccine-induced immunity towards survivin and IDO
      derived peptides can be achieved in combination with TMZ in patients mainly
      suffering from grade M1c melanoma including patients with brain metastases. A
      significant clinical activity could not be proven in this small study and a
      larger setup is needed to properly assess clinical efficacy.

PMID- 29057251
TI  - The RNA helicase DDX5 is a reprogramming roadblock.

PMID- 29057250
TI  - Stem-cell extracellular vesicles and lung repair.
AB  - Four out of the ten leading causes of morbidity and mortality worldwide are lung
      diseases. Despite advances in comprehending the pathophysiological mechanisms
      involved in these disorders, for several respiratory diseases, there is still no
      effective treatment able to stop their natural history or reverse the
      morphological and functional damage they cause. In this context, recent research
      has supported a potential role of cell therapy for lung diseases and critical
      illness. The anti-inflammatory, antifibrotic, and microbicidal effects of stem
      cells are mainly attributed to their secretome, which contains proteins, lipids,
      microRNAs, and mRNAs. These are secreted in the conditioned medium and are also
      present in extracellular vesicles (EVs). This review will provide a detailed
      discussion of the role of EVs produced by mesenchymal stromal cells in
      preclinical experimental models of pulmonary disorders and critical illness, as
      well as in ongoing clinical trials.

PMID- 29057253
TI  - Nicotinamide, iRPE-in-a dish, and age-related macular degeneration therapy
      development.

PMID- 29057252
TI  - GLIS1-3: emerging roles in reprogramming, stem and progenitor cell
      differentiation and maintenance.
AB  - Recent studies have provided evidence for a regulatory role of GLI-similar (GLIS)
      transcription factors in reprogramming, maintenance and differentiation of
      several stem and progenitor cell populations. GLIS1, in conjunction with several
      other reprogramming factors, was shown to markedly increase the efficiency of
      generating induced pluripotent stem cells (iPSC) from somatic cells. GLIS2 has
      been reported to contribute to the maintenance of the pluripotent state in hPSCs.
      In addition, GLIS2 has a function in regulating self-renewal of hematopoietic
      progenitors and megakaryocytic differentiation. GLIS3 plays a critical role
      during the development of several tissues. GLIS3 is able to promote reprogramming
      of human fibroblasts into retinal pigmented epithelial (RPE) cells. Moreover,
      GLIS3 is essential for spermatogonial stem cell renewal and spermatogonial
      progenitor cell differentiation. During pancreas development, GLIS3 protein is
      first detectable in bipotent pancreatic progenitors and pro-endocrine progenitors
      and plays a critical role in the generation of pancreatic beta cells. Here, we
      review the current status of the roles of GLIS proteins in the maintenance and
      differentiation of these different stem and progenitor cells.

PMID- 29057254
TI  - Learning to Drive Safely: Reasonable Expectations and Future Directions for the
      Learner Period.
AB  - The young driver problem is typified by high crash rates early in licensure that
      decline with experience, but are higher initially and decline more slowly for the
      youngest novices. Despite considerable effort, only Graduated Driver Licensing
      System (GDLS) policies have been shown to improve novice young driver safety
      outcomes. Unfortunately, GDLS policies are mostly limited to countries with a
      relatively young licensure age. Meanwhile, it is not entirely clear how GDLS and
      other young driver transportation safety efforts, including driver training and
      testing, supervised practice and parental management of young drivers, can best
      be configured. Notably, professional training can foster improvements in vehicle
      management skills that are necessary, but do not assure safe driving behavior.
      Substantial recent research has focused on training methods to improve driving
      skills, but the safety benefits of driver training have not been established.
      While prolonged practice driving increases experience and provides supervisors
      with opportunities to prepare novices for independent driving, the transition to
      independent driving challenges novices to employ, on their own, poorly-mastered
      skills under unfamiliar and complex driving conditions. Licensing policies and
      parental management practices can limit the complexity of driving conditions
      while novices gain needed driving experience. Nevertheless, an emerging body of
      literature suggests that future advances in training and supervision of novice
      teenage drivers might best focus on the translation of learning to independent
      driving by fostering safe driving attitudes and norms, judgment, dedicated
      attention to driving tasks and self-control at the wheel.

PMID- 29057255
TI  - Factors Influencing Learner Permit Duration.
AB  - An increasing number of countries are requiring an extended learner permit prior
      to independent driving. The question of when drivers begin the learner permit
      period, and how long they hold the permit before advancing to independent
      licensure has received little research attention. Licensure timing is likely to
      be related to "push" and "pull" factors which may encourage or inhibit the
      process. To examine this question, we recruited a sample of 90 novice drivers (49
      females and 41 males, average age of 15.6 years) soon after they obtained a
      learner permit and instrumented their vehicles to collect a range of driving
      data. Participants completed a series of surveys at recruitment related to
      factors that may influence licensure timing. Two distinct findings emerged from
      the time-to-event analysis that tested these push and pull factors in relation to
      licensure timing. The first can be conceptualized as teens' motivation to drive
      (push), reflected in a younger age when obtaining a learner permit and extensive
      pre-permit driving experience. The second finding was teens' perceptions of their
      parents' knowledge of their activities (pull); a proxy for a parents'
      attentiveness to their teens' lives. Teens who reported higher levels of their
      parents' knowledge of their activities took longer to advance to independent
      driving. These findings suggest time-to-licensure may be related to teens'
      internal motivation to drive, and the ability of parents to facilitate or impede
      early licensure.

PMID- 29057256
TI  - Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the
      Hearts of Down Syndrome Fetuses.
AB  - Dosage-dependent upregulation of most of chromosome 21 (Hsa21) genes has been
      demonstrated in heart tissues of fetuses with Down syndrome (DS). Also miRNAs
      might play important roles in the cardiac phenotype as they are highly expressed
      in the heart and regulate cardiac development. Five Hsa21 miRNAs have been well
      studied in the past: miR-99a-5p, miR-125b-2-5p, let-7c-5p, miR-155-5p, and miR
      802-5p but few information is available about their expression in trisomic
      tissues. In this study, we evaluated the expression of these miRNAs in heart
      tissues from DS fetuses, showing that miR-99a-5p, miR-155-5p, and let-7c-5p were
      overexpressed in trisomic hearts. To investigate their role, predicted targets
      were obtained from different databases and cross-validated using the gene
      expression profiling dataset we previously generated for fetal hearts. Eighty
      five targets of let-7c-5p, 33 of miR-155-5p, and 10 of miR-99a-5p were expressed
      in fetal heart and downregulated in trisomic hearts. As nuclear encoded
      mitochondrial genes were found downregulated in trisomic hearts and mitochondrial
      dysfunction is a hallmark of DS phenotypes, we put special attention to let-7c-5p
      and miR-155-5p targets downregulated in DS fetal hearts and involved in
      mitochondrial function. The let-7c-5p predicted target SLC25A4/ANT1 was
      identified as a possible candidate for both mitochondrial and cardiac anomalies.

PMID- 29057257
TI  - Serological Analysis and Drug Resistance of Chlamydia pneumoniae and Mycoplasma
      pneumoniae in 4500 Healthy Subjects in Shenzhen, China.
AB  - OBJECTIVE: To understand the prevalence and distribution of Chlamydia pneumoniae
      (CP) and Mycoplasma pneumoniae (MP) in the population and to provide a basis for
      the prevention and treatment of respiratory tract infection. METHODS: This study
      included a total of 4500 healthy subjects who were given physical examination in
      Shenzhen People's Hospital from January to December in 2016. Venous blood was
      drawn from people to detect the MP- and CP-specific IgG and IgM in the serum
      using chemiluminescence immunoassay (CLIA). The relationship of MP and CP
      infections with patient age, seasons, and percentage of infections was analyzed.
      CONCLUSION: CP and MP cause high rate of asymptomatic infection, which may be
      associated with the high incidence of CP and MP infection, especially in children
      and the elderly population. Therefore, the implementation of effective and
      practical prevention measures has become an urgent need. MP culture and drug
      sensitivity test should be performed as early as possible in patients with
      manifested MP infections in order to ensure timely and proper treatment and to
      reduce the emergence of drug-resistant strains.

PMID- 29057258
TI  - Therapeutic Approaches and Role of ncRNAs in Cardiovascular Disorders and Insulin
      Resistance.
AB  - Diseases resulting from alterations in gene expressions through mutations in the
      genes or through changes in the gene expression regulation could be identified
      through the analysis of RNA expressions. ncRNAs play a significant role in
      regulation of the gene expression by controlling the expression levels of the
      coding RNAs and other cellular processes. Discoveries have shown that the human
      genome is encoded with sequences responsible for the transcription of thousands
      of ncRNAs. Even though the studies conducted on ncRNAs are still at initial
      stages, facts established so far display biomarkers that confirm their
      relationship with certain diseases such as cancers, cardiovascular diseases, and
      insulin resistance. These studies have been facilitated with high throughput
      modern sequencing techniques such as microarrays and RNA sequencing. The data
      obtained through the above analysis are processed with the aid of existing
      databases, to deduce conclusions on different diagnostic biomarkers and
      therapeutic targets for specific diseases. This review focuses on the association
      of ncRNAs in disease prediction, focusing mainly on cardiovascular diseases and
      disorders caused by insulin resistance. The report also analyzes regulatory
      functions of ncRNAs and novel approaches used in disease therapeutics.

PMID- 29057259
TI  - Association between Exposure to Traffic-Related Air Pollution and Prevalence of
      Allergic Diseases in Children, Seoul, Korea.
AB  - Although there has been suggestive evidence of the association between TRAP and
      ADs, findings remained inconsistent possibly due to limited population. We
      investigated the association between TRAP and ADs in a large population of
      children with rich spatial coverage and expanded age span in Seoul, Korea. TRAP
      exposures were estimated by categorized proximity to the nearest major road
      (<=150, 150-300, 300-500, and >500 m) and density of major roads within 300
      meters from children's residences. We estimated the association between two TRAP
      exposures and three ADs using generalized mixed model after adjusting for
      individual characteristics. We also investigated whether the association varied
      by household and regional socioeconomic status. We found associations of atopic
      eczema with road density [OR = 1.08; 95% CI = 1.01-1.15] and road proximity
      [1.15, 1.01-1.32; 1.17, 1.03-1.34; and 1.16, 1.01-1.34 for <=150, 150-300, and
      300-500 m, resp., compared to >500 m]. There was no association with asthma and
      allergic rhinitis. Effect estimates were generally the highest in the low
      socioeconomic region. Children living in areas surrounded by large and busy roads
      were likely to be at greater risks for atopic eczema, with increased
      vulnerability when living in deprived areas.

PMID- 29057260
TI  - Gastrointestinal Motility, Mucosal Mast Cell, and Intestinal Histology in Rats:
      Effect of Prednisone.
AB  - Our aim was to verify the effects of prednisone related to gastrointestinal
      motility, intestinal histology, and mucosal mast cells in rats. Two-month-old
      male Wistar rats were randomly assigned to control group (vehicle) animals
      receiving saline 0.9% (n = 7) or treated orally with 0.625 mg/kg/day of
      prednisone (n = 7) or 2.5 mg/kg/day of prednisone (n = 7) during 15 days. Mast
      cells and other histologic analyses were performed in order to correlate to
      gastric emptying, cecum arrival, and small intestine transit evaluated by
      Alternating Current Biosusceptometry. Results showed that prednisone in adult
      rats increased the frequency of gastric contractions, hastened gastric emptying,
      slowed small intestinal transit, and reduced mucosal mast cells. Histologically,
      the treatment with both doses of prednisone decreased villus height, whereas
      longitudinal and circular muscles and crypt depth were not affected. These
      findings indicate an impairment of intestinal absorption which may be linked to
      several GI dysfunctions and symptoms. The relationship between gastrointestinal
      motor disorders and cellular immunity needs to be clarified in experimental
      studies since prednisone is one of the most prescribed glucocorticoids worldwide.

PMID- 29057261
TI  - Aprepitant for the Treatment of Chronic Refractory Pruritus.
AB  - Chronic pruritus is a difficult condition to treat and is associated with several
      comorbidities, including insomnia, depression, and decreased quality of life.
      Treatment for chronic itch includes corticosteroids, antihistamines, and systemic
      therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory
      treatments, including azathioprine, methotrexate, and cellcept. However, some
      patients still remain refractory to conventional therapy. Aprepitant is a
      neurokinin-1 receptor antagonist approved for the prevention of chemotherapy
      induced and postoperative nausea and vomiting (CINV, PONV). Recently, aprepitant
      has demonstrated effectiveness in several case series and open label trials in
      relieving pruritus for patients refractory to other treatments. Patients with
      pruritus associated with Sezary syndrome, mycosis fungoides, lung adenocarcinoma,
      breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease,
      hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin's lymphoma
      have experienced considerable symptom relief with short-term use of aprepitant
      (up to two weeks). Due to differences in reporting and evaluation of drug
      effects, the mechanism of aprepitant's role is difficult to understand based on
      the current literature. Herein, we evaluate aprepitant's antipruritic effects and
      discuss its mechanism of action and adverse effects. We propose that aprepitant
      is an alternative for patients suffering from pruritus who do not obtain enough
      symptom relief from conventional therapy.

PMID- 29057262
TI  - Relationship between Interferon Beta-1A Administration and Intracranial Vascular
      Tone Regulation in Patients with Relapsing-Remitting Multiple Sclerosis: A Pilot
      Study.
AB  - Interferon beta (IFN-beta) therapy is one of the most commonly prescribed
      immunomodulatory therapies in relapsing-remitting multiple sclerosis (RRMS). A
      reversible cerebral vasoconstriction syndrome (RCVS), associated with IFN-beta
      use, has been recently described. For this reason, we tested the effect of once a
      week intramuscular administration of IFN-beta-1A on the function of cerebral
      vessels in a cohort of RRMS patients. Using transcranial Doppler (TCD)
      ultrasound, we measured the mean blood flow velocity (MFV) in intracranial
      vessels 10 h after IFN-beta administration. Measurements showed a significant
      increase in MFV compared to the baseline values in some vessels.

PMID- 29057263
TI  - Sterilization of Biofilm on a Titanium Surface Using a Combination of Nonthermal
      Plasma and Chlorhexidine Digluconate.
AB  - Nosocomial infections caused by opportunistic bacteria pose major healthcare
      problem worldwide. Out of the many microorganisms responsible for such
      infections, Pseudomonas aeruginosa is a ubiquitous bacterium that accounts for 10
      20% of hospital-acquired infections. These infections have mortality rates
      ranging from 18 to 60% and the cost of treatment ranges from $20,000 to $80,000
      per infection. The formation of biofilms on medical devices and implants is
      responsible for the majority of those infections. Only limited progress has been
      made to prevent this issue in a safe and cost-effective manner. To address this,
      we propose employing jet plasma to break down and inactivate biofilms in vitro.
      Moreover, to improve the antimicrobial effect on the biofilm, a treatment method
      using a combination of jet plasma and a biocide known as chlorhexidine (CHX)
      digluconate was investigated. We found that complete sterilization of P.
      aeruginosa biofilms can be achieved after combinatorial treatment using plasma
      and CHX. A decrease in biofilm viability was also observed using confocal laser
      scanning electron microscopy (CLSM). This treatment method sterilized biofilm
      contaminated surfaces in a short treatment time, indicating it to be a potential
      tool for the removal of biofilms present on medical devices and implants.

PMID- 29057264
TI  - Icariin Attenuates Synaptic and Cognitive Deficits in an Abeta1-42-Induced Rat
      Model of Alzheimer's Disease.
AB  - Icariin (ICA), a prenylated flavanol glycoside present in abundant quantities in
      Epimedium sagittatum, has shown promise in the treatment and prevention of
      Alzheimer's disease. Damage to synaptic plasticity induced by amyloid-beta
      mediated neurotoxicity is considered a main pathological mechanism driving the
      learning and memory deficits present in patients with Alzheimer's disease. This
      study investigated the neuroprotective effects of icariin in an Abeta1-42-induced
      rat model of Alzheimer's disease. Our results showed that Abeta1-42 injection
      induced loss of learning and memory behaviour in the Morris water maze, which
      could be reversed with intragastric administration of ICA. Furthermore, ICA
      reversed decreases in PSD-95, BDNF, pTrkB, pAkt, and pCREB expressions and
      prevented deterioration of synaptic interface structure. These findings indicate
      that ICA may improve synaptic plasticity through the BDNF/TrkB/Akt pathway and
      provide further evidence for its clinical application to improve learning and
      memory in patients with Alzheimer's disease.

PMID- 29057265
TI  - Take-Home Trial Comparing Fast Fourier Transformation-Based and Filter Bank-Based
      Cochlear Implant Speech Coding Strategies.
AB  - Previous studies have demonstrated no improved or deteriorated speech
      intelligibility with the HiResolution Fidelity 120TM speech coding strategy
      (HiResF120) over the original HiRes strategy. Improved spectral and deteriorated
      temporal sensitivities have been shown, making it plausible that the beneficial
      effect in the spectral domain was offset by the worsened temporal sensitivity. We
      hypothesize that the implementation of fast Fourier transform (FFT) processing,
      instead of the traditionally used bandpass filters, explains the reduction of
      temporal sensitivity. In this study, spectral ripple discrimination, temporal
      modulation detection, and speech intelligibility in noise were assessed in a two
      week take-home trial with 3 speech coding strategies: one with conventional
      bandpass filters (HiRes), one with FFT-based filters (HiRes FFT), and one with
      FFT-based filters and current steering (HiRes Optima). One participant dropped
      out due to discomfort with both research programs. The 10 remaining participants
      performed equally well on all tasks with all three speech coding strategies,
      implying that FFT processing does not change the ability of CI recipients to
      discriminate spectral or temporal information or speech understanding.

PMID- 29057266
TI  - Tapered, Double-Lead Threads Single Implants Placed in Fresh Extraction Sockets
      and Healed Sites of the Posterior Jaws: A Multicenter Randomized Controlled Trial
      with 1 to 3 Years of Follow-Up.
AB  - PURPOSE: To evaluate the survival, success, and complication rates of tapered
      double-lead threads single implants, placed in fresh extraction sockets and
      healed sites of the posterior jaws. METHODS: The enrolled patients were randomly
      divided into 2 groups: in the test group (TG), all implants were inserted at the
      time of tooth extraction; in the control group (CG), all implants were placed 3
      months after extraction. The implants were followed for a period of 1 to 3 years
      after loading. The main outcomes were implant survival, complications, and
      implant-crown success. RESULTS: Ninety-two patients had 97 installed implants (49
      in the TG, 48 in the CG). Only two implants failed, in the TG; the survival rates
      were therefore 95.9% (47/49) and 100% (48/48) for TG and CG, respectively. In the
      surviving implants, no complications were reported, for an implant-crown success
      of 100%. CONCLUSIONS: Although a significant difference was found in the levels
      of primary stability between TG and CG, single implants placed in fresh
      extraction sockets and healed sites of the posterior jaws had similar survival
      and complication rates. Crestal bone levels and peri-implant bone resorption
      showed similar values. A longer follow-up period is however required, to confirm
      these positive outcomes.

PMID- 29057267
TI  - Profiling microRNA from Brain by Microarray in a Transgenic Mouse Model of
      Alzheimer's Disease.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs, which regulate numerous cell
      functions by targeting mRNA for cleavage or translational repression, and have
      been found to play an important role in Alzheimer's disease (AD). Our study aimed
      to identify differentially expressed miRNAs in AD brain as a reference of
      potential therapeutic miRNAs or biomarkers for this disease. We used amyloid
      precursor protein (APP) and presenilin 1 (PS1) double transgenic mice and age
      matched wild-type (WT) littermates to determine the expression of miRNAs in the
      brain. MiRNAs were profiled by microarray, and differentially expressed miRNAs
      underwent target prediction and enrichment analysis. Microarray analysis revealed
      56 differentially expressed miRNAs in AD mouse brain, which involved 39 miRNAs
      that were significantly upregulated and 19 that were downregulated at different
      ages. Among those miRNAs, a total of 11 miRNAs, including miR-342-3p, miR-342-5p,
      miR-376c-3p, and miR-301b-3p, were not only conserved in human but also predicted
      to have targets and signaling pathways closely related to the pathology of AD. In
      conclusion, in this study, differentially expressed miRNAs were identified in AD
      brain and proposed as biomarkers, which may have the potential to indicate AD
      progression. Despite being preliminary, these results may aid in investigating
      pathological hallmarks and identify effective therapeutic targets.

PMID- 29057268
TI  - Latent Class Analysis of Noninvasive Methods and Liver Biopsy in Chronic
      Hepatitis C: An Approach without a Gold Standard.
AB  - AIMS: To evaluate the applicability of the Latent Class Analysis (LCA) and
      accuracy of transient elastography (TE), aspartate-to-platelet-ratio-index
      (APRI), enhanced liver fibrosis (ELF), and liver biopsy (LB) for liver fibrosis
      assessment in a model without a gold standard. METHODS: Significant fibrosis was
      defined as TE >= 7.1 kPa, APRI >= 1.5, ELF >= 9.37, or LB METAVIR F >= 2.
      Cirrhosis was defined as TE >= 12.5 kPa, APRI >= 2.0, ELF >= 10.31, or LB as
      METAVIR F = 4. RESULTS: 117 patients with chronic hepatitis C were included. In
      the LCA, for significant fibrosis the sensitivities and specificities (95% CI)
      were 0.92 (0.86-0.98) and 0.79 (0.72-0.86) for TE; 0.47 (0.40-0.54) and 0.99
      (0.95-1.00) for APRI; 0.81 (0.74-0.88) and 0.78 (0.71-0.85) for ELF; and 0.86
      (0.68-1.00) and 0.91 (0.79-1.00) for LB. For cirrhosis, the sensitivities and
      specificities were 0.92 (0.76-1.00) and 0.94 (0.91-0.97) for TE; 0.57 (0.37-0.77)
      and 0.97 (0.93-1.00) for APRI; 0.94 (0.84-1.00) and 0.88 (0.82-0.94) for ELF; and
      0.30 (0.12-0.48) and 1.00 for LB. CONCLUSION: LCA was useful to evaluate accuracy
      of methods for liver fibrosis staging. Sensitivities and specificities of
      noninvasive methods were increased in LCA compared to the use of LB as the gold
      standard.

PMID- 29057270
TI  - Differential Diagnosis of Parotid Gland Tumors: Role of Shear Wave Elastography.
AB  - AIM: To create a predictive score for the discrimination between benign and
      malignant parotid tumors using elastographic parameters and to compare its
      sensitivity and specificity with standard ultrasound. METHODS: A total of 124
      patients with parotid gland lesions for whom surgery was planned were examined
      using conventional ultrasound, Doppler examination, and shear wave elastography.
      Results of the examinations were compared with those ones of histology. RESULTS:
      There were 96 benign and 28 malignant lesions in our cohort. Blurred tumor margin
      alone proved to be an excellent predictor of malignancy with the sensitivity of
      79% and specificity of 97%. Enlarged cervical lymph nodes, tumor vascularisation,
      microcalcifications presence, homogeneous echogenicity, and bilateral occurrence
      also discriminated between benign and malignant tumors. However, their inclusion
      in a predictive model did not improve its performance. Elastographic parameters
      (the stiffness maxima and minima ratio being the best) also exhibited significant
      differences between benign and malignant tumors, but again, their inclusion did
      not significantly improve the predictive power of the blurred margin classifier.
      CONCLUSION: Even though elastography satisfactorily distinguishes benign from
      malignant lesions on its own, it hardly provides any additional value in
      evaluation of biological character of parotid gland tumors when used as an
      adjunct to regular ultrasound examination.

PMID- 29057271
TI  - Overexpression of MicroRNA-145 Ameliorates Astrocyte Injury by Targeting
      Aquaporin 4 in Cerebral Ischemic Stroke.
AB  - Cerebral ischemic stroke, which affects the global population, is a major disease
      with high incidence, mortality, and disability. Accumulating evidence has
      indicated that abnormal microRNA (miRNA) expression plays essential roles in the
      pathologies of ischemic stroke. Yet, the underlying regulatory mechanism of
      miRNAs in cerebral ischemic stroke remains unclear. We investigated the role of
      miR-145 in cerebral ischemic stroke and its potential mechanism in a model using
      primary cultured astrocytes. We detected the expression levels of miR-145 and its
      target gene AQP4 and assessed the role of miR-145 in cell death and apoptosis
      caused by oxygen-glucose deprivation (OGD). Bioinformatics analysis was used to
      explore the targets of miR-145. miR-145 expression levels were significantly
      decreased in primary astrocytes subjected to OGD. miR-145 overexpression promoted
      astrocyte health and inhibited OGD-induced apoptosis. AQP4 was a direct target of
      miR-145, and miR-145 suppressed AQP4 expression. Moreover, AQP4 enhanced
      astrocyte injury in ischemic stroke, and AQP4 knockdown diminished the miR-145
      mediated protective effect on ischemic injury. Taken together, our results show
      that miR-145 plays an important role in protecting astrocytes from ischemic
      injury by downregulating AQP4 expression. These findings may highlight a novel
      therapeutic target in cerebral ischemic stroke.

PMID- 29057269
TI  - Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches
      after Stroke: Current Status, Rationale, and Challenges.
AB  - A better understanding of the neural substrates that underlie motor recovery
      after stroke has led to the development of innovative rehabilitation strategies
      and tools that incorporate key elements of motor skill relearning, that is,
      intensive motor training involving goal-oriented repeated movements. Robotic
      devices for the upper limb are increasingly used in rehabilitation. Studies have
      demonstrated the effectiveness of these devices in reducing motor impairments,
      but less so for the improvement of upper limb function. Other studies have begun
      to investigate the benefits of combined approaches that target muscle function
      (functional electrical stimulation and botulinum toxin injections), modulate
      neural activity (noninvasive brain stimulation), and enhance motivation (virtual
      reality) in an attempt to potentialize the benefits of robot-mediated training.
      The aim of this paper is to overview the current status of such combined
      treatments and to analyze the rationale behind them.

PMID- 29057272
TI  - Hydroethanolic Extract of Strychnos pseudoquina Accelerates Skin Wound Healing by
      Modulating the Oxidative Status and Microstructural Reorganization of Scar Tissue
      in Experimental Type I Diabetes.
AB  - The effect of topical application of ointment based on Strychnos pseudoquina
      hydroethanolic extract in the cutaneous wounds healing in diabetic rats was
      evaluated. Samples of S. pseudoquina were submitted to phytochemical prospection
      and in vitro antioxidant assay. Thirty Wistar rats were divided into 5 groups:
      Sal-wounds treated with 0.9% saline solution; VH-wounds treated with 0.6 g of
      lanolin cream (vehicle); SS-wounds treated with silver sulfadiazine cream (10
      mg/g); ES5- and ES10-wounds treated with an ointment of S. pseudoquina extract,
      5% and 10%, respectively. Fragments of wounds were removed for histological and
      biochemical analysis every 7 days during 21 days. ES showed equivalent levels per
      gram of extract of total phenols and flavonoids equal to 122.04 mg for TAE and
      0.60 mg for RE. The chlorogenic acid was one of the major constituents. S.
      pseudoquina extract presented high antioxidant potential in vitro. ES5 and ES10
      showed higher wound healing rate and higher amount of cells, blood vessels, and
      type III and I collagen. The oxidative stress markers were lower in the ES5 and
      ES10 groups, while the antioxidants enzymes levels were higher. Ointment based on
      S. pseudoquina extract promotes a fast and efficient cutaneous repair in diabetic
      rats.

PMID- 29057273
TI  - Correlates of Calcaneal Quantitative Ultrasound Parameters in Patients with
      Diabetes: The Study on the Assessment of Determinants of Muscle and Bone Strength
      Abnormalities in Diabetes.
AB  - OBJECTIVE: Quantitative ultrasound (QUS) provides an estimate of bone mineral
      density (BMD) and also evaluates bone quality, which has been related to
      increased fracture risk in people with diabetes. This study aimed at assessing
      the correlates of calcaneal QUS parameters in diabetic subjects encompassing
      various degrees of micro and macrovascular complications and a wide-range of
      peripheral nerve function. METHODS: Four hundred consecutive diabetic patients
      were examined by QUS to obtain values of broadband ultrasound attenuation (BUA),
      the speed of sound (SOS), quantitative ultrasound index (QUI), and BMD. RESULTS:
      Among surrogate measures of complications, sensory and motor nerve amplitude and
      heart rate response to cough test and standing correlated with QUS parameters at
      univariate analysis, together with age, body mass index (BMI), waist
      circumference, lipid profile, and renal function. Multivariate analysis revealed
      that BUA, SOS, QUI, and BMD were independently associated with age, male gender,
      hemoglobin A1c, BMI (or fat, but not fat-free mass), and somatic and autonomic
      nerve function parameters. CONCLUSIONS: These data indicate that peripheral nerve
      dysfunction is associated with worse QUS parameters, possibly contributing to
      increased fracture risk in diabetes. The positive relation of QUS measures with
      adiposity needs further investigation. This trial is registered with
      ClinicalTrials.gov (NCT01600924).

PMID- 29057274
TI  - Effectiveness of Vildagliptin in Clinical Practice: Pooled Analysis of Three
      Korean Observational Studies (the VICTORY Study).
AB  - The present observational study aimed to evaluate the clinical effectiveness of
      vildagliptin with metformin in Korean patients with type 2 diabetes mellitus
      (T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the
      vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective
      observational study of vildagliptin/metformin (fixed DC or free DC). The
      effectiveness endpoint was the proportion of patients who achieved a glycemic
      target (HbA1c) of <=7.0% at 24 weeks. In total, 4303 patients were included in
      the analysis; of these, 2087 patients were eligible. The mean patient age was
      56.99 +/- 11.25 years. Overall, 58.94% patients achieved an HbA1c target of
      <=7.0% at 24 weeks. The glycemic target achievement rate was significantly
      greater in patients with baseline HbA1c < 7.5% versus >=7.5% (84.64% versus
      43.97%), receiving care at the hospital versus clinic (67.95% versus 52.33%), and
      receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%).
      Multivariate logistic regression analysis indicated that disease duration (P <
      0.0001), baseline HbA1c (P < 0.0001), and DC type (P = 0.0103) had significant
      effects on drug effectiveness. Vildagliptin plus metformin appeared as an
      effective treatment option for patients with T2DM in clinical practice settings
      in Korea.

PMID- 29057275
TI  - Clinical Outcomes of Donor Sites After Osteochondral Graft Harvest From Healthy
      Knees.
AB  - BACKGROUND: The use of autologous osteochondral grafts has become popular in the
      treatment of small, isolated, well-contained articular cartilage defects.
      However, donor site morbidity is a problem, and few reports are available of
      donor site morbidity after mosaicplasty. PURPOSE: To examine the clinical
      outcomes of donor sites after osteochondral grafts from healthy knees. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Between September 1997 and
      September 2011, there were 40 patients (40 knees; 32 men, 8 women; 31 right
      knees, 9 left knees) with asymptomatic osteochondral graft donor sites used for
      autologous transfer; all had a follow-up period of >2 years. The mean patient age
      at surgery was 21.0 years (range, 12-58 years). The recipient sites included the
      elbow (n = 28), contralateral knee (n = 5), and ankle (n = 7). The mean diameter
      of the grafted plugs was 7.5 mm (range, 4.5-9 mm), and the mean number of grafted
      plugs was 2.2 (range, 1-3). At a mean follow-up of 43.1 months (range, 24-177
      months), knee symptoms, return to sport, ability to sit straight in Japanese
      style, and radiological changes of the patellofemoral joint were evaluated.
      Whether operative age, follow-up period, and diameter or number of the grafted
      plugs were risk factors was analyzed statistically. Significance was defined as P
      < .05. RESULTS: Thirty-four patients had no knee symptoms, and 4 patients had
      occasional mild knee pain. Two patients underwent reoperation for arthrofibrosis
      and not for cartilage defect. Twenty-seven patients had complete return to
      sports, and 32 patients could sit straight; donor site morbidity was not the
      cause of failure to return to sports or inability to sit straight. The
      radiological changes became worse in 3 patients, and the risk factor for
      degenerative change was older operative age. CONCLUSION: When osteochondral plugs
      were obtained from healthy knees, 34 patients (85%) were asymptomatic at follow
      up. No donor site defects required surgical intervention due to persistent
      symptoms.

PMID- 29057277
TI  - A method for evaluating cocaine-induced social preference in rats.
AB  - Drug addicts are extremely sensitive to cues that predict drug availability and
      exposure to these cues can facilitate drug relapse. Cues vary in their nature but
      can include drug-associated paraphernalia, environmental contexts, and discrete
      conditioned stimuli (e.g., advertisements). One cue that has recently been
      heavily investigated is that of social interaction. To date, it has been
      demonstrated that when cocaine is conditioned with social interaction, place
      preference for cocaine significantly increases, suggesting that the presence of
      social interaction during a drug-associated "high" enhances the magnitude of drug
      reward. When social interaction is provided in a mutually exclusive, non-drug
      environment though, it can serve as a preventative stimulus towards cocaine
      seeking. What remains unknown is whether contact with rats associated with drug
      experience facilitates preferential social interactions for those rats. The first
      step in answering this question is to determine if rats can behaviorally
      discriminate between drug-associated and non-drug-associated conspecifics, much
      like humans can differentiate their "drug-friends" from their non-drug-using
      friends. Using a custom social interaction chamber, in which rats were able to
      interact with two distinct conspecifics via holes in a boundary wall, we
      demonstrate that rats exhibit more interactive and investigative behavior towards
      a partner that was consistently present during the drug-state, than a partner
      that was present when the rat was "sober". It is our hope that this protocol will
      contribute to the development of models designed to study social cue-induced
      reinstatement, and related neural substrates, and will ultimately contribute to
      the treatment of substance use disorders.

PMID- 29057278
TI  - Healthcare Access and Utilization among Korean Americans: The Mediating Role of
      English Use and Proficiency.
AB  - The literature suggests that Korean Americans underutilize health services.
      Cultural factors and language barriers appear to influence this pattern of low
      utilization but studies on the relationships among length of stay in the US,
      English use and proficiency, and utilization of health services among Korean
      Americans have yielded inconsistent results. This study examines whether English
      language use and proficiency plays a mediating role in the relationships between
      length of stay in the US and health insurance coverage, access to and use of
      care. Structural equation modeling was used for mediation analysis with multiple
      dependent variables among Korean Americans (N = 555) using baseline data from a
      large trial designed to increase Hepatitis B testing. The results show 36% of the
      total effect of proportion of lifetime in the US on having health insurance was
      significantly mediated by English use and proficiency (indirect effect = 0.166,
      SE = 0.07, p<.05; direct effect = 0.296, SE = 0.13, p<.05). Proportion of
      lifetime in the US was not associated with usual source of care and health
      service utilization. Instead, health care utilization was primarily driven by
      having health insurance and a usual source of care, further underscoring the
      importance of these factors. A focus on increasing English use and proficiency
      and insurance coverage among older, female, less educated Korean Americans has
      the potential to mitigate health disparities associated with reduced access to
      health services in this population.

PMID- 29057276
TI  - Genetic Correlates of Spirituality/Religion and Depression: A Study in Offspring
      and Grandchildren at High and Low Familial Risk for Depression.
AB  - RATIONALE: Possible genetic correlates of spirituality and depression have been
      identified in community samples. We investigate some of the previously identified
      candidates in a sample of families at both high and low-risk for depression.
      METHOD: Offspring and grandchildren of individuals at high and low-risk for
      depression, participating in a multi-wave thirty-year longitudinal study, were
      assessed for seven SNPS drawn from four single gene candidates associated with
      systems implicated in both depression and spirituality: Serotonin (5-HT1B and 5
      HT2A), Dopamine (DRD2), Oxytocin (OT) and Monoamine Vesicular Transporter
      (VMAT1). RESULTS: Dopamine (DRD2) Serotonin (5-HT1B), their Transporter (VMAT1)
      and Oxytocin (OXTR) were positively associated with a high level of importance of
      spirituality or religion (S/R) in the group at low familial risk for depression.
      DRD2 minor allele was associated with both lifetime major depressive disorder
      (MDD) and spirituality in the low-risk group for depression. No SNPs were related
      to S/R in the group at high familial risk for depression. OXTR was associated
      with lifetime MDD in the full sample. CONCLUSION: Genes for dopamine, serotonin,
      their vesicular transporter, and oxytocin may be associated with S/R in people at
      low familial risk for depression. Genes for dopamine may be associated both with
      S/R and increased risk for depression in people at low-risk for depression,
      suggesting a common pathway or physiology to mild to moderate depression. MDD is
      associated with oxytocin across risk groups. In the high-risk group, phenotypic
      expression of S/R may be suppressed. IMPLICATIONS: The shared association of DRD2
      by S/R and depression, generally found to be inversely related, calls for further
      research on their common physiological pathways, and the phenotypic expression of
      these pathways based upon use and environment. Prevention for offspring at high
      familial risk for depression might include support for the development of child
      spirituality.

PMID- 29057279
TI  - Breast cancer survivors' beliefs and preferences regarding technology-supported
      sedentary behavior reduction interventions.
AB  - PURPOSE: Less time spent in sedentary behaviors is associated with improved
      health and disease outcomes in breast cancer survivors. However, little is known
      about survivors' interest in sedentary behavior reduction interventions and how
      to effectively reduce this risk behavior. The purpose of this study was to
      explore breast cancer survivors' interest in and preferences for technology
      supported sedentary behavior reduction interventions. METHODS: Breast cancer
      survivors [n=279; Mage =60.7 (SD=9.7)] completed a battery of online
      questionnaires. Descriptive statistics were calculated for all data. To examine
      potential relationships between demographic, disease and behavioral factors, and
      survivors' interest in a technology-supported sedentary behavior reduction
      intervention, we conducted logistic regression analyses. These same factors were
      examined in relation to the perceptions of the effectiveness of such intervention
      using multiple regression analyses. RESULTS: On average, survivors spent 10.1
      (SD=4.3) hours/day in sedentary activity. They believed prolonged periods of
      sedentary behavior were harmful to their health (87.0%) and that reducing
      sedentary behavior could improve their health (88.4%). Survivors believed they
      should move around after 30-60 (56.7%) or >=60 (29.9%) minutes of sedentary
      behavior and indicated they were most likely to replace sedentary behaviors with
      walking around (97.1%) or walking in place (73.4%). The majority of survivors
      (79.9%) was interested in participating in a technology-supported sedentary
      behavior reduction intervention and indicated they would use a smartphone
      application (61.3%) 2-3 times/day (48.0%), 6 to 7 days/week (52.0%). Most
      survivors (73.5%) believed reminders would help them decrease sedentary behavior
      and preferred they be delivered after sitting for 60 minutes (60.5%) via
      vibrations on a wrist worn activity tracker (77.3%) or text messages (54.4%).
      CONCLUSIONS: Technology-supported sedentary behavior reduction interventions may
      be feasible and acceptable to breast cancer survivors. Data regarding user
      preferences for content, features, delivery mode and design will aid researchers
      in developing sedentary interventions that are potentially more relevant and
      effective from the outset.

PMID- 29057280
TI  - Multidrug Resistant Pseudomonas aeruginosa Causing Prosthetic Valve Endocarditis:
      A Genetic-Based Chronicle of Evolving Antibiotic Resistance.
AB  - Background.  Successful treatment of infections caused by multidrug-resistant
      (MDR) Pseudomonas aeruginosa is thwarted by the emergence of antibiotic
      resistance and biofilm formation on prosthetic devices. Our aims were to decipher
      the molecular basis of resistance in a unique case of prosthetic valve
      endocarditis (PVE) caused by MDR P. aeruginosa. Methods.  Five sequential MDR P.
      aeruginosa blood isolates collected during a 7-month period were recovered from a
      patient suffering from PVE previously exposed to beta-lactam antibiotics. Minimum
      inhibitory concentrations (MICs) of several classes of antibiotics were used to
      indicate clinical resistance characteristics; relatedness of the isolates was
      determined using multilocus sequence typing and repetitive sequence-based
      polymerase chain reaction. Amplification and sequencing of regulatory and
      resistance genes was performed. Results.  All isolates belonged to ST 298,
      possessed blaPDC-16, and were resistant to fluoroquinolones and carbapenems. In
      the course of therapy, we observed a >2-fold increase in cephalosporin resistance
      (4 ug/mL to >16 ug/mL). Sequencing of the AmpC regulator, ampR, revealed a D135N
      point mutation in cephalosporin-resistant isolates. Common carbapenemase genes
      were not identified. All isolates demonstrated a premature stop codon at amino
      acid 79 of the outer membrane protein OprD and mutations in the quinolone
      resistance-determining regions of gyrA and parC. Point mutations in nalC, an
      efflux pump regulator, were also observed. Conclusions.  In this analysis, we
      chart the molecular evolution of beta-lactam resistance in a case of PVE. We show
      that mutations in regulatory genes controlling efflux and cephalosporinase
      production contributed to the MDR phenotype.

PMID- 29057281
TI  - Atg5flox-Derived Autophagy-Deficient Model of Pompe Disease: Does It Tell the
      Whole Story?

PMID- 29057282
TI  - CerebraLux: a low-cost, open-source, wireless probe for optogenetic stimulation.
AB  - The use of optogenetics to activate or inhibit neurons is an important toolbox
      for neuroscientists. Several optogenetic devices are in use. These range from
      wired systems where the optoprobe is physically connected to the light source by
      a tether, to wireless systems that are remotely controlled. There are advantages
      and disadvantages of both; the wired systems are lightweight but limit movement
      due to the tether, and wireless systems allow unrestricted movement but may be
      heavier than wired systems. Both systems can be expensive to install and use. We
      have developed a low cost, wireless optogenetic probe, CerebraLux, built from off
      the-shelf components. CerebraLux consists of two separable units; an optical
      component consisting of the baseplate holding the fiber-optic in place and an
      electronic component consisting of a light-emitting diode, custom-printed circuit
      board, an infrared receiver, microcontroller, and a rechargeable, lightweight
      lithium polymer battery. The optical component (0.5 g) is mounted on the head
      permanently, whereas the electronic component (2.3 g) is removable and is applied
      for each experiment. We describe the device, provide all designs and
      specifications, the methods to manufacture and use the device in vivo, and
      demonstrate feasibility in a mouse behavioral paradigm.

PMID- 29057283
TI  - Cortical responses to shape-from-motion stimuli in the infant.
AB  - Our ability to extract three-dimensional (3-D) object structure from motion
      carried information is a basic visual capacity that is fundamental to object
      perception. Despite a rich body of behavioral work demonstrating that infants are
      sensitive to motion-carried information from the early months of life, little is
      known about the cortical networks that support infants' use of motion-carried
      information to extract 3-D object structure. This study assessed patterns of
      cortical activation in infants aged 4 to 6 months as they viewed two types of
      visual stimuli: (a) shape-from-motion (SFM) displays, where coherent motion of
      randomly distributed dots gave rise to the percept of 3-D shape and (b) random
      motion (RM) displays, where dots' motions lacked a coherent structure and gave
      rise to the percept of randomly moving dots. Functional near-infrared
      spectroscopy was used to assess activation in occipital, inferior parietal, and
      posterior temporal cortex. The optical imaging data revealed differential
      responding to SFM and RM in lower level object processing areas than typically
      observed in the adult. Possible explanations for this pattern of results are
      considered.

PMID- 29057284
TI  - Association between hemodynamic activity and motor performance in six-month-old
      full-term and preterm infants: a functional near-infrared spectroscopy study.
AB  - This study aimed to assess task-induced activation in motor cortex and its
      association with motor performance in full-term and preterm born infants at six
      months old. A cross-sectional study of 73 six-month-old infants was conducted (35
      full-term and 38 preterm infants). Motor performance was assessed using the
      Bayley Scales of Infant Development third edition-Bayley-III. Brain hemodynamic
      activity during motor task was measured by functional near-infrared spectroscopy
      (fNIRS). Motor performance was similar in full-term and preterm infants. However,
      differences in hemodynamic response were identified. Full terms showed a more
      homogeneous unilateral and contralateral activated area, whereas in preterm-born
      the activation response was predominantly bilateral. The full-term group also
      exhibited a shorter latency for the hemodynamic response than the preterm group.
      Hemodynamic activity in the left sensorimotor region was positively associated
      with motor performance measured by Bayley-III. The results highlight the adequacy
      of fNIRS to assess differences in task-induced activation in sensorimotor cortex
      between groups. The association between motor performance and the hemodynamic
      activity require further investigation and suggest that fNIRS can become a
      suitable auxiliary tool to investigate aspects of neural basis on early
      development of motor abilities.

PMID- 29057285
TI  - Using prerecorded hemodynamic response functions in detecting prefrontal pain
      response: a functional near-infrared spectroscopy study.
AB  - Currently, there is no method for providing a nonverbal objective assessment of
      pain. Recent work using functional near-infrared spectroscopy (fNIRS) has
      revealed its potential for objective measures. We conducted two fNIRS scans
      separated by 30 min and measured the hemodynamic response to the electrical
      noxious and innocuous stimuli over the anterior prefrontal cortex (aPFC) in 14
      subjects. Based on the estimated hemodynamic response functions (HRFs), we first
      evaluated the test-retest reliability of using fNIRS in measuring the pain
      response over the aPFC. We then proposed a general linear model (GLM)-based
      detection model that employs the subject-specific HRFs from the first scan to
      detect the pain response in the second scan. Our results indicate that fNIRS has
      a reasonable reliability in detecting the hemodynamic changes associated with
      noxious events, especially in the medial portion of the aPFC. Compared with a
      standard HRF with a fixed shape, including the subject-specific HRFs in the GLM
      allows for a significant improvement in the detection sensitivity of aPFC pain
      response. This study supports the potential application of individualized
      analysis in using fNIRS and provides a robust model to perform objective
      determination of pain perception.

PMID- 29057286
TI  - Recent advances in edge illumination x-ray phase-contrast tomography.
AB  - Edge illumination (EI) is an x-ray phase-contrast imaging technique, exploiting
      sensitivity to x-ray refraction to visualize features, which are often not
      detected by conventional absorption-based radiography. The method does not
      require a high degree of spatial coherence and is achromatic and, therefore, can
      be implemented with both synchrotron radiation and commercial x-ray tubes. Using
      different retrieval algorithms, information about an object's attenuation,
      refraction, and scattering properties can be obtained. In recent years, a
      theoretical framework has been developed that enables EI computed tomography (CT)
      and, hence, three-dimensional imaging. This review provides a summary of these
      advances, covering the development of different image acquisition schemes,
      retrieval approaches, and applications. These developments constitute an integral
      part in the transformation of EI CT into a widely spread imaging tool for use in
      a range of fields.

PMID- 29057287
TI  - Dimension reduction technique using a multilayered descriptor for high-precision
      classification of ovarian cancer tissue using optical coherence tomography: a
      feasibility study.
AB  - Optical coherence tomography (OCT) yields microscopic volumetric images
      representing tissue structures based on the contrast provided by elastic light
      scattering. Multipatient studies using OCT for detection of tissue abnormalities
      can lead to large datasets making quantitative and unbiased assessment of
      classification algorithms performance difficult without the availability of
      automated analytical schemes. We present a mathematical descriptor reducing the
      dimensionality of a classifier's input data, while preserving essential
      volumetric features from reconstructed three-dimensional optical volumes. This
      descriptor is used as the input of classification algorithms allowing a detailed
      exploration of the features space leading to optimal and reliable classification
      models based on support vector machine techniques. Using imaging dataset of
      paraffin-embedded tissue samples from 38 ovarian cancer patients, we report
      accuracies for cancer detection [Formula: see text] for binary classification
      between healthy fallopian tube and ovarian samples containing cancer cells.
      Furthermore, multiples classes of statistical models are presented demonstrating
      [Formula: see text] accuracy for the detection of high-grade serous, endometroid,
      and clear cells cancers. The classification approach reduces the computational
      complexity and needed resources to achieve highly accurate classification, making
      it possible to contemplate other applications, including intraoperative surgical
      guidance, as well as other depth sectioning techniques for fresh tissue imaging.

PMID- 29057288
TI  - Fully automated segmentation of prostate whole gland and transition zone in
      diffusion-weighted MRI using convolutional neural networks.
AB  - Prostate cancer is a leading cause of cancer-related death among men.
      Multiparametric magnetic resonance imaging has become an essential part of the
      diagnostic evaluation of prostate cancer. The internationally accepted
      interpretation scheme (Pi-Rads v2) has different algorithms for scoring of the
      transition zone (TZ) and peripheral zone (PZ) of the prostate as tumors can
      appear different in these zones. Computer-aided detection tools have shown
      different performances in TZ and PZ and separating these zones for training and
      detection is essential. The TZ-PZ segmentation which requires the segmentation of
      prostate whole gland and TZ is typically done manually. We present a fully
      automatic algorithm for delineation of the prostate gland and TZ in diffusion
      weighted imaging (DWI) via a stack of fully convolutional neural networks. The
      proposed algorithm first detects the slices that contain a portion of prostate
      gland within the three-dimensional DWI volume and then it segments the prostate
      gland and TZ automatically. The segmentation stage of the algorithm was applied
      to DWI images of 104 patients and median Dice similarity coefficients of 0.93 and
      0.88 were achieved for the prostate gland and TZ, respectively. The detection of
      image slices with and without prostate gland had an average accuracy of 0.97.

PMID- 29057289
TI  - Acoustic beam anomalies in automated breast imaging.
AB  - In B-mode imaging of the dependent or compressed breast, wave incidence at steep
      angles can change propagation directions and induce areas of signal dropout. To
      evaluate the image anomalies in reasonable simulation times, we performed full
      wave studies for center frequencies of 1 and 4 MHz. Speed of sound and density of
      skin, typical coupling gel, and adipose tissue were assigned to the test
      couplant. Compared with commercial gel, skin-like couplant reduced the dropout
      area at 1 and 4 MHz by 57.1% and 96.7%, respectively, consistent with a decreased
      average beam deflection in the breast. Conversely, the adipose-like couplant
      increased the dropout area from that of simulated commercial gel by 26.5% and
      36.7% at 1 and 4 MHz, respectively. In addition, the skin-like couplant resulted
      in the greatest beam deflection inside the breast among all couplants. The
      findings could aid the use of three-dimensional simulations to design ultrasound
      couplants for beam passage through tissue boundaries at steep angles to improve
      corrections of signal dropout and defocusing and in compound imaging.

PMID- 29057290
TI  - Feature analysis of cell nuclear chromatin distribution in support of cervical
      cytology.
AB  - Cytology, a method of estimating cancer or cellular atypia from microscopic
      images of scraped specimens, is used according to the pathologist's experience to
      diagnose cases based on the degree of structural changes and atypia. Several
      methods of cell feature quantification, including nuclear size, nuclear shape,
      cytoplasm size, and chromatin texture, have been studied. We focus on chromatin
      distribution in the cell nucleus and propose new feature values that indicate the
      chromatin complexity, spreading, and bias, including convex hull ratio on
      multiple binary images, intensity distribution from the gravity center, and
      tangential component intensity and texture biases. The characteristics and
      cellular classification accuracies of the proposed features were verified through
      experiments using cervical smear samples, for which clear nuclear morphologic
      diagnostic criteria are available. In this experiment, we also used a stepwise
      support vector machine to create a machine learning model and a cross-validation
      algorithm with which to derive identification accuracy. Our results demonstrate
      the effectiveness of our proposed feature values.

PMID- 29057291
TI  - Deep Learning Based Binaural Speech Separation in Reverberant Environments.
AB  - Speech signal is usually degraded by room reverberation and additive noises in
      real environments. This paper focuses on separating target speech signal in
      reverberant conditions from binaural inputs. Binaural separation is formulated as
      a supervised learning problem, and we employ deep learning to map from both
      spatial and spectral features to a training target. With binaural inputs, we
      first apply a fixed beamformer and then extract several spectral features. A new
      spatial feature is proposed and extracted to complement the spectral features.
      The training target is the recently suggested ideal ratio mask. Systematic
      evaluations and comparisons show that the proposed system achieves very good
      separation performance and substantially outperforms related algorithms under
      challenging multi-source and reverberant environments.

PMID- 29057292
TI  - Positional Tremor and its Treatment.
AB  - BACKGROUND: Positional tremors arise when a patient's tremor is brought on during
      specific positioning of the involved body part. They can be distinguished from
      postural tremor, wherein a patient's tremor is elicited in any posture, and from
      task-specific tremor, wherein a patient's tremor occurs only during a certain
      task. CASES: We describe two cases of positional tremor that are markedly
      improved with botulinum toxin injection. DISCUSSION: The term "positional" is a
      valuable descriptor for tremors. In patients with positional tremor, botulinum
      toxin may be beneficial for treatment. Lidocaine injection provides a transient
      way to test for the appropriateness of botulinum toxin injection in these
      patients.

PMID- 29057293
TI  - Measuring Text Difficulty Using Parse-Tree Frequency.
AB  - Text simplification often relies on dated, unproven readability formulas. As an
      alternative and motivated by the success of term familiarity, we test a
      complementary measure: grammar familiarity. Grammar familiarity is measured as
      the frequency of the 3rd level sentence parse tree and is useful for evaluating
      individual sentences. We created a database of 140K unique 3rd level parse
      structures by parsing and binning all 5.4M sentences in English Wikipedia. We
      then calculated the grammar frequencies across the corpus and created 11
      frequency bins. We evaluate the measure with a user study and corpus analysis.
      For the user study, we selected 20 sentences randomly from each bin, controlling
      for sentence length and term frequency, and recruited 30 readers per sentence
      (N=6,600) on Amazon Mechanical Turk. We measured actual difficulty
      (comprehension) using a Cloze test, perceived difficulty using a 5-point Likert
      scale, and time taken. Sentences with more frequent grammatical structures, even
      with very different surface presentations, were easier to understand, perceived
      as easier and took less time to read. Outcomes from readability formulas
      correlated with perceived but not with actual difficulty. Our corpus analysis
      shows how the metric can be used to understand grammar regularity in a broad
      range of corpora.

PMID- 29057294
TI  - Integrating Quantum Dots and Dielectric Mie Resonators: A Hierarchical
      Metamaterial Inheriting the Best of Both.
AB  - Nanoscale dielectric resonators and quantum-confined semiconductors have enabled
      unprecedented control over light absorption and excited charges, respectively. In
      this work, we embed luminescent silicon nanocrystals (Si-NCs) into a 2D array of
      SiO2 nanocylinders and experimentally prove a powerful concept: the resulting
      metamaterial preserves the radiative properties of the Si-NCs and inherits the
      spectrally selective absorption properties of the nanocylinders. This
      hierarchical approach provides increased photoluminescence (PL) intensity
      obtained without utilizing any lossy plasmonic components. We perform rigorous
      calculations and predict that a freestanding metamaterial enables tunable
      absorption peaks up to 50% in the visible spectrum, in correspondence with the
      nanocylinder Mie resonances and of the grating condition in the array. We
      experimentally detect extinction spectral peaks in the metamaterial, which drive
      enhanced absorption in the Si-NCs. Consequently, the metamaterial features
      increased PL intensity, obtained without affecting the PL lifetime, angular
      pattern, and extraction efficiency. Remarkably, our best-performing metamaterial
      shows +30% PL intensity achieved with a lower amount of Si-NCs, compared to an
      equivalent planar film without nanocylinders, resulting in a 3-fold average PL
      enhancement per Si-NC. The principle demonstrated here is general, and the Si-NCs
      can be replaced with other semiconductor quantum dots, rare-earth ions, or
      organic molecules. Similarly, the dielectric medium can be adjusted on purpose.
      This spectral selectivity of absorption paves the way for an effective light down
      conversion scheme to increase the efficiency of solar cells. We envision the use
      of this hierarchical design for other efficient photovoltaic, photocatalytic, and
      artificial photosynthetic devices with spectrally selective absorption and
      enhanced efficiency.

PMID- 29057295
TI  - Multicolor Stimulated Emission Depletion (STED) Microscopy to Generate High
      resolution Images of Respiratory Syncytial Virus Particles and Infected Cells.
AB  - Human respiratory syncytial virus (RSV) infection in human lung epithelial A549
      cells induces filopodia, cellular protrusions consisting of F-actin, that extend
      to neighboring uninfected cells (Mehedi et al., 2016). High-resolution imaging
      via stimulated emission depletion (STED) microscopy revealed filamentous RSV
      particles along these filopodia, suggesting that filopodia facilitate RSV cell-to
      cell spread (Mehedi et al., 2016). In this protocol, we describe how to fix,
      permeabilize, immunostain, and mount RSV-infected A549 cells for STED imaging. We
      show that STED increases resolution compared to confocal microscopy, which can be
      further improved by image processing using deconvolution software.

PMID- 29057296
TI  - Emotion in the Law and the Lab: The Case of Graphic Cigarette Warnings.
AB  - The decision in RJ Reynolds vs. FDA (2012) to invalidate FDA's proposed graphic
      health warnings was based in part on the reasoning that the proposed graphic
      warnings cued emotional responses and therefore could not be considered
      "factual." However, this reasoning demonstrated the courts' fundamental
      misunderstanding of current behavioral-science research. In contrast to the
      courts' artificial separation of emotions from fact, we synthesize and interpret
      relevant research in basic decision sciences and describe an evidence-based
      characterization of how emotions influence consumer decision making through
      multiple mechanisms. We then explore how behavioral research gets "lost in
      translation" in the legal process and recommend ways that behavioral scientists
      can work with attorneys to remedy this problem. In order for science-based
      tobacco regulation to survive legal challenges from the tobacco industry, courts
      must have access to and be able to understand and apply the relevant research.
      Accordingly, behavioral laboratory researchers must consider the courts as an
      additional audience when designing research and reporting results. Researchers
      wishing to influence policy should also work closely with public health lawyers
      to have the greatest impact on the legal system.

PMID- 29057297
TI  - Does Certificate of Need Minimize Intensity Modulated Radiation Therapy Use in
      Patients with Low Risk Prostate Cancer?
AB  - PURPOSE: Certificate of Need (CON) laws are optional from state to state, and are
      meant to limit proliferation of certain unnecessary medical facilities.
      Theoretically, CON should limit the use of IMRT (intensity modulated radiation
      therapy) in the population who likely would benefit from it the least: older or
      debilitated men with low risk prostate cancer. We evaluated the effect of CON on
      IMRT use in these patients in a population-based cohort. METHODS AND MATERIALS:
      Using the Surveillance, Epidemiology and End Results (SEER) database linked with
      Medicare files, we identified male residents of SEER regions who were diagnosed
      in 2004-2009 with low- risk prostate cancer (T1, Gleason<=6, PSA<10) and were
      either >=70 years old or >=65 years old with Charlson comorbidity score >= 2. The
      endpoint was percentage of newly diagnosed patients who were treated with IMRT
      within 12 month of cancer diagnosis. Logistic regression was used to assess the
      impact of CON laws on IMRT use. RESULTS: Over 37% (4,491) of the patients came
      from states with radiation oncology CON laws, whereas 63% (7,572) came from non
      CON states. IMRT was performed on 30% of CON patients versus 28% of non-CON
      patients. Logistic regression analysis revealed that IMRT was utilized more often
      in CON states than in non-CON states, odds ratio (OR) 1.13 (95% CI 1.04-1.23,
      p=0.006). CONCLUSIONS: CON laws do not effectively limit use of IMRT in older or
      debilitated patients with low risk prostate cancer.

PMID- 29057298
TI  - Saposin B Binds the Lipofuscin Bisretinoid A2E and Prevents its Enzymatic and
      Photooxidation.
AB  - Vitamin A based bisretinoid accumulation is a major focus in the study of macular
      degeneration. Whether specific endogenous lysosomal proteins can bind A2E, a
      pronounced bisretinoid in lipofuscin granules in retinal pigment epithelial
      cells, and interfere with enzymatic or photoinduced oxidation of such, has not
      been explored. Herein, using fluorescence and electronic absorption spectroscopy
      and mass spectrometry, we demonstrate that Saposin B, a critical protein in the
      degradation of sulfatides and "flushing" of lipids, can bind A2E, preventing its
      H2O2-dependent enzymatic oxidation by horseradish peroxidase and photooxidation
      by blue light (lambda=450-460 nm).

PMID- 29057299
TI  - Viagra releases the brakes on melanoma growth.
AB  - Use of the phosphodiesterase 5 (PDE5) blocker sildenafil (Viagra) has been linked
      to an increased risk of melanoma. In a recent study we discovered a growth
      promoting cGMP pathway in melanoma cells. cGMP degradation via PDE5 acts as a
      brake on this pathway. Inhibition of PDE5 releases this brake, providing a
      mechanism for the promelanoma effects of sildenafil.

PMID- 29057300
TI  - Targeting ATR/CHK1 pathway in acute myeloid leukemia to overcome chemoresistance.
AB  - Resistance of acute myeloid leukemia to current therapies leads to frequent
      relapses. Identification of molecular mechanisms involved in chemoresistance
      constitutes a key challenge to define new therapeutic concepts. Here, we show
      that the ATR/CHK1 pathway, essential in maintaining genomic stability, is
      involved in resistance and proliferation characteristics of leukemic cells.

PMID- 29057301
TI  - Uncovering a novel pathway for p16 silencing: Therapeutic implications for lung
      cancer.
AB  - A key step during onset of most cases of non-small cell lung cancer (NSCLC) is
      the loss of the tumor suppressor p16INK4a (best known as p16), commonly due to
      promoter hypermethylation. We recently reported a novel regulatory pathway
      involving E6-associated protein and cell division control protein 6, which
      provides a methylation-independent mechanism for p16 silencing in patients with a
      particularly aggressive form of NSCLC.

PMID- 29057302
TI  - Effective modulation of stromal signaling through ROCK inhibition: Is it all in
      the timing?
AB  - Our recent publication demonstrates that transient inhibition of Rho-associated
      kinase signaling within stroma, significantly decreased in vivo primary tumor
      growth, metastasis and improved response to standard-of-care therapy in
      pancreatic cancer. Automated analysis of collagen organization in patient tumors
      may present a promising tool to predict response to our proposed treatment.

PMID- 29057303
TI  - RRM2B: An oxygen-requiring protein with a role in hypoxia.
AB  - How tumor cells adapt and survive under hypoxia significantly impacts patient
      prognosis. We recently demonstrated that the oxygen-requiring ribonucleotide
      reductase (RNR) enzyme, which provides cells with deoxyribonucleotides, responds
      to limited oxygen availability by switching small subunits from RRM2 to RRM2B.
      This property of RNR is essential for hypoxic cell viability and therefore
      contributes to the most aggressive and therapy-resistant fraction of tumors.

PMID- 29057304
TI  - Augmented capacity to clear misfolded proteins: An intrinsic characteristic of
      tumor cells?

PMID- 29057305
TI  - PERK and filamin A in actin cytoskeleton remodeling at ER-plasma membrane contact
      sites.
AB  - The endoplasmic reticulum (ER) stress sensor protein kinase RNA-like endoplasmic
      reticulum kinase (PERK) plays a major role during the unfolded protein response
      (UPR), mainly through eIF2alpha phosphorylation. We uncovered that PERK, by
      interacting with Filamin A, elicits F-actin remodeling required for ER-plasma
      membrane contact site formation after ER-Ca2+ depletion, through a UPR
      independent mechanism.

PMID- 29057306
TI  - Inhibiting system xC- and glutathione biosynthesis - a potential Achilles' heel
      in mutant-p53 cancers.
AB  - Effective therapeutic strategies to target mutant tumor protein p53 (TP53, best
      known as p53) cancers remain an unmet medical need. We found that mutant p53
      impairs the function of nuclear factor (erythroid-derived 2)-like 2 (NFE2L2,
      commonly known as NRF2), suppresses solute carrier family 7 member 11 (SLC7A11)
      expression, and diminishes cellular glutamate/cystine exchange. This decreases
      glutathione biosynthesis, resulting in redox imbalance. Mutant p53 tumors are
      thus inherently susceptible to further perturbations of the SLC7A11/glutathione
      axis.

PMID- 29057307
TI  - JumonjiC demethylase inhibitors show potential for targeting chemotherapy
      resistant lung cancers.
AB  - Resistance to standard taxane-platin chemotherapy and tumor relapse are a major
      challenge in the treatment of non-small cell lung cancers (NSCLC). Our recent
      study identified JumonjiC demethylase inhibitors as a highly potent therapeutic
      strategy for targeting chemoresistant tumors and for preventing the emergence of
      drug-tolerant clones from taxane-platin treated NSCLCs.

PMID- 29057308
TI  - RAS oncogenes direct metastasis.
AB  - RAS genes are cardinal driver oncogenes frequently and differentially mutated
      across bodily tumors. Their tumorigenic potential has been mainly ascribed to
      autonomous promotion of tumor cell proliferation and survival. However, recent
      evidence shows that RAS oncogenes also function to define metastatic tropism.
      Interestingly, RAS-driven metastasis is mediated by distinct chemokine sets that
      signal to endothelial and myeloid cells.

PMID- 29057309
TI  - Direct pro-apoptotic role for NPM1 as a regulator of PIDDosome formation.
AB  - Despite being frequently mutated or deregulated in acute myeloid leukemia (AML)
      and many other cancers, the mechanisms by which nucleophosmin (NPM1) regulates
      oncogenesis remain elusive. We found that NPM1 plays a direct and conserved role
      in DNA damage-induced assembly of the PIDDosome complex, the activating platform
      for caspase-2. This function is carried in the nucleolus and is essential for
      caspase-2-mediated apoptosis in response to a variety of DNA injuries.

PMID- 29057310
TI  - Mitophagy, metabolism, and cell fate.
AB  - Mitophagy is the process by which cells eliminate damaged or superfluous
      mitochondria by degrading them within lysosomes. We show that during development,
      selective removal of mitochondria by autophagy induces a metabolic shift toward
      glycolysis that is essential for differentiation of several cell types. These
      findings suggest potential applications of cell-fate manipulation strategies
      targeting mitophagy.

PMID- 29057311
TI  - Targeting RNA binding protein in prostate cancer.
AB  - RNA binding protein (RBP) controls multiple aspects of RNA metabolism and plays
      crucial roles in many physiopathological contexts, including cancer. We recently
      identified an RBP HNRNPL as a novel prostate cancer dependency via regulation of
      RNA splicing, suggesting the potential to target RBP or RBP-RNA interaction to
      treat cancer.

PMID- 29057312
TI  - Autophagosomal membranes assemble at ER-plasma membrane contact sites.
AB  - The biogenesis of autophagosome, the double membrane bound organelle related to
      macro-autophagy, is a complex event requiring numerous key-proteins and membrane
      remodeling events. Our recent findings identify the extended synaptotagmins,
      crucial tethers of Endoplasmic Reticulum-plasma membrane contact sites, as key
      regulators of this molecular sequence.

PMID- 29057313
TI  - A lipid off-switch for mTORC1.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of
      metabolism, cell growth and survival. Our finding that local phosphatidylinositol
      3,4-bisphosphate [PI(3,4)P2] synthesis at late endosomes/ lysosomes by class II
      PI3Kbeta (PI3KC2beta) represses mTORC1 identifies PI3KC2beta as a pharmacological
      target for the treatment of diabetes and cancer.

PMID- 29057314
TI  - Lung squamous cell carcinoma exhibits a targetable glucose dependency unique
      among non-small cell lung cancers.
AB  - Cancer cells consume high amounts of glucose for their cellular bioenergetic and
      anabolic requirements, relying on glucose to fuel their growth. We recently
      reported that lung squamous cell carcinoma, a major subtype of non-small cell
      lung cancer (NSCLC), exhibits remarkably elevated glucose transporter GLUT1
      (encoded by SLC2A1) expression and glucose dependency, while another subtype of
      NSCLC, lung adenocarcinoma, shows significant glucose independence. Our findings
      highlight the metabolic heterogeneity of glucose metabolism among lung cancer
      subtypes, which can be exploited for targeted lung cancer therapies.

PMID- 29057316
TI  - Life After Being a Pathology Department Chair II: Lessons Learned.
AB  - The 2016 Association of Pathology Chairs annual meeting featured a discussion
      group of Association of Pathology Chairs senior fellows (former chairs of
      academic departments of pathology who have remained active in Association of
      Pathology Chairs) that focused on how they decided to transition from the chair,
      how they prepared for such transition, and what they did after the transition. At
      the 2017 annual meeting, the senior fellows (encompassing 481 years of chair
      service) discussed lessons they learned from service as chair. These lessons
      included preparation for the chairship, what they would have done differently as
      chair, critical factors for success as chair, factors associated with failures,
      stress reduction techniques for themselves and for their faculty and staff,
      mechanisms for dealing with and avoiding problems, and the satisfaction they
      derived from their service as chair. It is reasonable to assume that these
      lessons may be representative of those learned by chairs of other specialties as
      well as by higher-level academic administrators such as deans, vice presidents,
      and chief executive officers. Although the environment for serving as a
      department chair has been changing dramatically, many of the lessons learned by
      former chairs are still valuable for current chairs of any length of tenure.

PMID- 29057315
TI  - Mitochondrial impairment in microglia amplifies NLRP3 inflammasome
      proinflammatory signaling in cell culture and animal models of Parkinson's
      disease.
AB  - The NLRP3 inflammasome signaling pathway is a major contributor to the
      neuroinflammatory process in the central nervous system. Oxidative stress and
      mitochondrial dysfunction are key pathophysiological processes of many chronic
      neurodegenerative diseases, including Parkinson's disease (PD). However, the
      inter-relationship between mitochondrial defects and neuroinflammation is not
      well understood. In the present study, we show that impaired mitochondrial
      function can augment the NLRP3 inflammasome-driven proinflammatory cascade in
      microglia. Primary mouse microglia treated with the common inflammogen LPS
      increased NLRP3 and pro-IL-1beta expression. Interestingly, exposure of LPS
      primed microglial cells to the mitochondrial complex-I inhibitory pesticides
      rotenone and tebufenpyrad specifically potentiated the NLRP3 induction, ASC speck
      formation and pro-IL-1beta processing to IL-1beta in a dose-dependent manner,
      indicating that mitochondrial impairment heightened the NLRP3 inflammasome
      mediated proinflammatory response in microglia. The neurotoxic pesticide-induced
      NLRP3 inflammasome activation was accompanied by bioenergetic defects and
      lysosomal dysfunction in microglia. Furthermore, the pesticides enhanced
      mitochondrial ROS generation in primary microglia, while amelioration of
      mitochondria-derived ROS by the mitochondria-targeted antioxidant mito-apocynin
      completely abolished IL-1beta release, indicating mitochondrial ROS drives
      potentiation of the NLRP3 inflammasome in microglia. Exposure to conditioned
      media obtained from mitochondrial inhibitor-treated, LPS-primed microglial cells,
      but not unprimed cells, induced dopaminergic neurodegeneration in cultured
      primary mesencephalic and human dopaminergic neuronal cells (LUHMES). Notably,
      our in vivo results with chronic rotenone rodent models of PD further support the
      activation of proinflammatory NLRP3 inflammasome signaling due to mitochondrial
      dysfunction. Collectively, our results demonstrate that mitochondrial impairment
      in microglia can amplify NLRP3 inflammasome signaling, which augments the
      dopaminergic neurodegenerative process.

PMID- 29057317
TI  - STEERing an IDeA in Undergraduate Research at a Rural Research Intensive
      University.
AB  - This study documents outcomes, including student career choices, of the North
      Dakota Institutional Development Award Networks of Biomedical Research Excellence
      program that provides 10-week, summer undergraduate research experiences at the
      University of North Dakota School of Medicine and Health Sciences. Program
      evaluation initiated in 2008 and, to date, 335 students have completed the
      program. Of the 335, 214 students have successfully completed their bachelor's
      degree, 102 are still undergraduates, and 19 either did not complete a bachelor's
      degree or were lost to follow-up. The program was able to track 200 of the 214
      students for education and career choices following graduation. Of these 200, 76%
      continued in postgraduate health-related education; 34.0% and 20.5% are enrolled
      in or have completed MD or PhD programs, respectively. Other postbaccalaureate
      pursuits included careers in pharmacy, optometry, dentistry, public health,
      physical therapy, nurse practitioner, and physician's assistant, accounting for
      an additional 21.5%. Most students electing to stop formal education at the
      bachelor's degree also entered fields related to health care or science,
      technology, engineering, and mathematics (19.5%), with only a small number of the
      200 students tracked going into service or industries which lacked an association
      with the health-care workforce (4.5%). These student outcomes support the concept
      that participation in summer undergraduate research boosts efforts to populate
      the pipeline of future researchers and health professionals. It is also an
      indication that future researchers and health professionals will be able to
      communicate the value of research in their professional and social associations.
      The report also discusses best practices and issues in summer undergraduate
      research for students originating from rural environments.

PMID- 29057318
TI  - A cluster-based approach to compression of Quality Scores.
AB  - Massive amounts of sequencing data are being generated thanks to advances in
      sequencing technology and a dramatic drop in the sequencing cost. Storing and
      sharing this large data has become a major bottleneck in the discovery and
      analysis of genetic variants that are used for medical inference. As such,
      lossless compression of this data has been proposed. Of the compressed data, more
      than 70% correspond to quality scores, which indicate the sequencing machine
      reliability when calling a particular basepair. Thus, to further improve the
      compression performance, lossy compression of quality scores is emerging as the
      natural candidate. Since the data is used for genetic variants discovery, lossy
      compressors for quality scores are analyzed in terms of their rate-distortion
      performance, as well as their effect on the variant callers. Previously proposed
      algorithms do not do well under all performance metrics, and are hence unsuitable
      for certain applications. In this work we propose a new lossy compressor that
      first performs a clustering step, by assuming all the quality scores sequences
      come from a mixture of Markov models. Then, it performs quantization of the
      quality scores based on the Markov models. Each quantizer targets a specific
      distortion to optimize for the overall rate-distortion performance. Finally, the
      quantized values are compressed by an entropy encoder. We demonstrate that the
      proposed lossy compressor outperforms the previously proposed methods under all
      analyzed distortion metrics. This suggests that the effect that the proposed
      algorithm will have on any downstream application will likely be less noticeable
      than that of previously proposed lossy compressors. Moreover, we analyze how the
      proposed lossy compressor affects Single Nucleotide Polymorphism (SNP) calling,
      and show that the variability introduced on the calls is considerably smaller
      than the variability that exists between different methodologies for SNP calling.

PMID- 29057319
TI  - Strong amplitude and phase modulation of optical spatial coherence with surface
      plasmon polaritons.
AB  - The degree of optical spatial coherence-a fundamental property of light that
      describes the mutual correlations between fluctuating electromagnetic fields-has
      been proven challenging to control at the micrometer scale. We use surface
      plasmon polaritons-evanescent waves excited on both surfaces of a thin metal film
      as a means to mix the random fluctuations of the incident electromagnetic fields
      at the slit locations of a Young's double-slit interferometer. Strong tunability
      of the complex degree of spatial coherence of light is achieved by finely varying
      the separation distance between the two slits. Continuous modulation of the
      degree of spatial coherence with amplitudes ranging from 0 to 80% allows us to
      transform totally incoherent incident light into highly coherent light and vice
      versa. These findings pave the way for alternative methods to engineer flat
      optical elements with multifunctional capabilities beyond conventional refractive
      and diffractive-based photonic metasurfaces.

PMID- 29057320
TI  - Bioinspired phase-separated disordered nanostructures for thin photovoltaic
      absorbers.
AB  - The wings of the black butterfly, Pachliopta aristolochiae, are covered by micro-
      and nanostructured scales that harvest sunlight over a wide spectral and angular
      range. Considering that these properties are particularly attractive for
      photovoltaic applications, we analyze the contribution of these micro- and
      nanostructures, focusing on the structural disorder observed in the wing scales.
      In addition to microspectroscopy experiments, we conduct three-dimensional
      optical simulations of the exact scale structure. On the basis of these results,
      we design nanostructured thin photovoltaic absorbers of disordered nanoholes,
      which combine efficient light in-coupling and light-trapping properties together
      with a high angular robustness. Finally, inspired by the phase separation
      mechanism of self-assembled biophotonic nanostructures, we fabricate these
      bioinspired absorbers using a scalable, self-assembly patterning technique based
      on the phase separation of binary polymer mixture. The nanopatterned absorbers
      achieve a relative integrated absorption increase of 90% at a normal incident
      angle of light to as high as 200% at large incident angles, demonstrating the
      potential of black butterfly structures for light-harvesting purposes in thin
      film solar cells.

PMID- 29057321
TI  - Abundance and local-scale processes contribute to multi-phyla gradients in global
      marine diversity.
AB  - Among the most enduring ecological challenges is an integrated theory explaining
      the latitudinal biodiversity gradient, including discrepancies observed at
      different spatial scales. Analysis of Reef Life Survey data for 4127 marine
      species at 2406 coral and rocky sites worldwide confirms that the total ecoregion
      richness peaks in low latitudes, near +15 degrees N and -15 degrees S. However,
      although richness at survey sites is maximal near the equator for vertebrates, it
      peaks at high latitudes for large mobile invertebrates. Site richness for
      different groups is dependent on abundance, which is in turn correlated with
      temperature for fishes and nutrients for macroinvertebrates. We suggest that
      temperature-mediated fish predation and herbivory have constrained mobile
      macroinvertebrate diversity at the site scale across the tropics. Conversely, at
      the ecoregion scale, richness responds positively to coral reef area,
      highlighting potentially huge global biodiversity losses with coral decline.
      Improved conservation outcomes require management frameworks, informed by
      hierarchical monitoring, that cover differing site- and regional-scale processes
      across diverse taxa, including attention to invertebrate species, which appear
      disproportionately threatened by warming seas.

PMID- 29057322
TI  - Temporal variation in pelagic food chain length in response to environmental
      change.
AB  - Climate variability alters nitrogen cycling, primary productivity, and dissolved
      oxygen concentration in marine ecosystems. We examined the role of this
      variability (as measured by six variables) on food chain length (FCL) in the
      California Current (CC) by reconstructing a time series of amino acid-specific
      delta15N values derived from common dolphins, an apex pelagic predator, and using
      two FCL proxies. Strong declines in FCL were observed after the 1997-1999 El Nino
      Southern Oscillation (ENSO) event. Bayesian models revealed longer FCLs under
      intermediate conditions for surface temperature, chlorophyll concentration,
      multivariate ENSO index, and total plankton volume but not for hypoxic depth and
      nitrate concentration. Our results challenge the prevalent paradigm that
      suggested long-term stability in the food web structure in the CC and, instead,
      reveal that pelagic food webs respond strongly to disturbances associated with
      ENSO events, local oceanography, and ongoing changes in climate.

PMID- 29057324
TI  - Upscaling species richness and abundances in tropical forests.
AB  - The quantification of tropical tree biodiversity worldwide remains an open and
      challenging problem. More than two-fifths of the number of worldwide trees can be
      found either in tropical or in subtropical forests, but only ~0.000067% of
      species identities are known. We introduce an analytical framework that provides
      robust and accurate estimates of species richness and abundances in biodiversity
      rich ecosystems, as confirmed by tests performed on both in silico-generated and
      real forests. Our analysis shows that the approach outperforms other methods. In
      particular, we find that upscaling methods based on the log-series species
      distribution systematically overestimate the number of species and abundances of
      the rare species. We finally apply our new framework on 15 empirical tropical
      forest plots and quantify the minimum percentage cover that should be sampled to
      achieve a given average confidence interval in the upscaled estimate of
      biodiversity. Our theoretical framework confirms that the forests studied are
      comprised of a large number of rare or hyper-rare species. This is a signature of
      critical-like behavior of species-rich ecosystems and can provide a buffer
      against extinction.

PMID- 29057323
TI  - Identification of XBP1-u as a novel regulator of the MDM2/p53 axis using an shRNA
      library.
AB  - Cell cycle progression is a tightly controlled fundamental process in living
      cells, with any defects being closely linked to various abnormalities. The tumor
      suppressor p53/p21 axis is a core pathway controlling cell cycle progression;
      however, its regulatory mechanism has not been fully elucidated. In an effort to
      unravel this crucial network, we screened a short hairpin RNA expression vector
      library and identified unspliced X-box binding protein 1 (XBP1-u) as a novel and
      critical regulator of the p53/p21 axis. Specifically, XBP1-u negatively regulates
      the p53/p21 axis by enhancing p53 ubiquitination, which in turn down-regulates
      p21 expression. We show that XBP1-u suppression induces G0-G1 phase arrest and
      represses cell proliferation. We further report that the carboxyl terminus of
      XBP1-u, which differs from that of its spliced form (XBP1-s) due to a codon
      shift, binds and stabilizes mouse double minute homolog 2 (MDM2) protein, a
      negative regulator of p53, by inhibiting its self-ubiquitination. Concomitantly,
      XBP-u overexpression enhances tumorigenesis by positively regulating MDM2.
      Together, our findings suggest that XBP1-u functions far beyond being merely a
      precursor of XBP1-s and, instead, is involved in fundamental biological
      processes. Furthermore, this study provides new insights regarding the regulation
      of the MDM2/p53/p21 axis.

PMID- 29057325
TI  - Comprehensive vaccine design for commensal disease progression.
AB  - Commensal organisms with the potential to cause disease pose a challenge in
      developing treatment options. Using the example featured in this study,
      pneumococcal disease begins with Streptococcus pneumoniae colonization, followed
      by triggering events that prompt the release of a virulent subpopulation of
      bacteria. Current vaccines focus on colonization prevention, which poses
      unintended consequences of serotype niche replacement. In this study, noncovalent
      colocalization of two classes of complementary antigens, one to prevent the
      colonization of the most aggressive S. pneumoniae serotypes and another to
      restrict virulence transition, provides complete vaccine effectiveness in animal
      subjects and the most comprehensive coverage of disease reported to date. As a
      result, the proposed vaccine formulation offers universal pneumococcal disease
      prevention with the prospect of effectively managing a disease that afflicts tens
      to hundreds of millions globally. The approach more generally puts forth a
      balanced prophylactic treatment strategy in response to complex commensal-host
      dynamics.

PMID- 29057326
TI  - Accelerating metabolism and transmembrane cation flux by distorting red blood
      cells.
AB  - Under static conditions, mammalian red blood cells (RBCs) require a continuous
      supply of energy, typically via glucose, to maintain their biconcave disc shape.
      Mechanical distortion, in a complementary way, should lead to increased energy
      demand that is manifest in accelerated glycolysis. The experimental challenge in
      observing this phenomenon was met by reversibly and reproducibly distorting the
      cells and noninvasively measuring glycolytic flux. This was done with a gel
      distorting device that was coupled with 13C nuclear magnetic resonance (NMR)
      spectroscopy. We measured [3-13C]l-lactate production from [1,6-13C]d-glucose in
      the RBCs suspended in gelatin gels, and up to 90% rate enhancements were
      recorded. Thus, for the first time, we present experiments that demonstrate the
      linkage of mechanical distortion to metabolic changes in whole mammalian cells.
      In seeking a mechanism for the linkage between shape and energy supply, we
      measured transmembrane cation flux with Cs+ (as a K+ congener) using 133Cs NMR
      spectroscopy, and the cation flux was increased up to fivefold. The postulated
      mechanism for these notable (in terms of whole-body energy consumption) responses
      is stimulation of Ca-adenosine triphosphatase by increased transmembrane flux of
      Ca2+ via the channel protein Piezo1 and increased glycolysis because its flux is
      adenosine triphosphate demand-regulated.

PMID- 29057327
TI  - Shaping highly regular glass architectures: A lesson from nature.
AB  - Demospongiae is a class of marine sponges that mineralize skeletal elements, the
      glass spicules, made of amorphous silica. The spicules exhibit a diversity of
      highly regular three-dimensional branched morphologies that are a paradigm
      example of symmetry in biological systems. Current glass shaping technology
      requires treatment at high temperatures. In this context, the mechanism by which
      glass architectures are formed by living organisms remains a mystery. We uncover
      the principles of spicule morphogenesis. During spicule formation, the process of
      silica deposition is templated by an organic filament. It is composed of
      enzymatically active proteins arranged in a mesoscopic hexagonal crystal-like
      structure. In analogy to synthetic inorganic nanocrystals that show high spatial
      regularity, we demonstrate that the branching of the filament follows specific
      crystallographic directions of the protein lattice. In correlation with the
      symmetry of the lattice, filament branching determines the highly regular
      morphology of the spicules on the macroscale.

PMID- 29057330
TI  - Validation of a White-light 3D Body Volume Scanner to Assess Body Composition.
AB  - INTRODUCTION: Estimating body fat content has shown to be a better predictor of
      adiposity-related cardiovascular risk than the commonly used body mass index
      (BMI). The white-light 3D body volume index (BVI) scanner is a non-invasive
      device normally used in the clothing industry to assess body shapes and sizes. We
      assessed the hypothesis that volume obtained by BVI is comparable to the volume
      obtained by air displacement plethysmography (Bod-Pod) and thus capable of
      assessing body fat mass using the bi-compartmental principles of body
      composition. METHODS: We compared BVI to Bod-pod, a validated bicompartmental
      method to assess body fat percent that uses pressure/volume relationships in
      isothermal conditions to estimate body volume. Volume is then used to calculate
      body density (BD) applying the formula density=Body Mass/Volume. Body fat mass
      percentage is then calculated using the Siri formula (4.95/BD - 4.50) * 100.
      Subjects were undergoing a wellness evaluation. Measurements from both devices
      were obtained the same day. A prediction model for total Bod-pod volume was
      developed using linear regression based on 80% of the observations (N=971), as
      follows: Predicted Bod-pod Volume (L)=9.498+0.805*(BVI volume, L)-0.0411*(Age,
      years)-3.295*(Male=0, Female=1)+0.0554*(BVI volume, L)*(Male=0,
      Female=1)+0.0282*(Age, years)*(Male=0, Female=1). Predictions for Bod-pod volume
      based on the estimated model were then calculated for the remaining 20% (N=243)
      and compared to the volume measured by the Bod-pod. RESULTS: Mean age among the
      971 individuals was 41.5 +/- 12.9 years, 39.4% were men, weight 81.6 +/- 20.9 kg,
      BMI was 27.8 +/- 6.3kg/m2. Average difference between volume measured by Bod-pod-
      predicted volume by BVI was 0.0 L, median: -0.4 L, IQR: -1.8 L to 1.5 L,
      R2=0.9845. Average difference between body fat measured-predicted was-1%, median:
      -2.7%, IQR: -13.2 to 9.9, R2=0.9236. CONCLUSION: Volume and BFM can be estimated
      by using volume measurements obtained by a white- light 3D body scanner and the
      prediction model developed in this study.

PMID- 29057329
TI  - Rapid Diagnosis of Tuberculosis from Analysis of Urine Volatile Organic
      Compounds.
AB  - The World Health Organization has called for simple, sensitive, and non-sputum
      diagnostics for tuberculosis. We report development of a urine tuberculosis test
      using a colorimetric sensor array (CSA). The sensor comprised of 73 different
      indicators captures high-dimensional, spatiotemporal signatures of volatile
      chemicals emitted by human urine samples. The sensor responses to 63 urine
      samples collected from 22 tuberculosis cases and 41 symptomatic controls were
      measured under five different urine test conditions. Basified testing condition
      yielded the best accuracy with 85.5% sensitivity and 79.5% specificity. The CSA
      urine assay offers desired features needed for tuberculosis diagnosis in endemic
      settings.

PMID- 29057328
TI  - Cancer Prevention and Treatment by Wholistic Nutrition.
AB  - Cancer is traditionally considered a genetic disease. It starts with a gene
      mutation, often caused by environmental carcinogens that are enzymatically
      activated to metabolites that covalently bind to DNA. If these now-damaged
      carcinogen-DNA adducts are not repaired before the cell replicates, they result
      in a mutation, which is inherited by daughter cells and their subsequent progeny.
      Still more mutations are added that are thought to advance cellular independence,
      metastasis, and drug resistance, among other characteristics typically observed
      for advanced cancer. The stages of initiation, promotion and progression of
      cancer by mutations infer irreversibility because back mutations are exceedingly
      rare. Thus, treatment protocols typically are designed to remove or kill cancer
      cells by surgery, chemotherapy, immunotherapy and/or radiotherapy. However,
      empirical evidence has existed to show a fundamentally different treatment
      option. For example, the promotion of cancer growth and development in laboratory
      animals initiated by a powerful mutagen/carcinogen can be repetitively turned on
      and off by non-mutagenic mechanisms, even completely, by modifying the
      consumption of protein at relevant levels of intake. Similar but less
      substantiated evidence also exists for other nutrients and other cancer types.
      This suggests that ultimate cancer development is primarily a nutrition
      responsive disease rather than a genetic disease, with the understanding that
      nutrition is a comprehensive, wholistic biological effect that reflects the
      natural contents of nutrients and related substances in whole, intact food. This
      perspective sharply contrasts with the contemporary inference that nutrition is
      the summation of individual nutrients acting independently. The spelling of
      'holism' with the 'w' is meant to emphasize the empirical basis for this
      function. The proposition that wholistic nutrition controls and even reverses
      disease development suggests that cancer may be treated by nutritional
      intervention.

PMID- 29057331
TI  - Crystallographic Data Support the Carousel Mechanism of Water Supply to the
      Oxygen-Evolving Complex of Photosystem II.
AB  - Photosystem II (PSII) oxidizes water to produce oxygen through a four-step
      photocatalytic cycle. Understanding PSII structure-function relations is
      important for the development of biomimetic photocatalytic systems. The quantum
      mechanics/molecular mechanics (QM/MM) analysis of substrate water binding to the
      oxygen-evolving complex (OEC) has suggested a rearrangement of water ligands in a
      carousel mechanism around a key Mn center. Here, we find that the most recently
      reported X-ray free-electron laser (XFEL) crystallographic data obtained for the
      dark-stable S1 state and the doubly flashed S3 state at 2.25 A resolution support
      the carousel mechanism. The features in the XFEL data and QM/MM model-simulated
      difference Fourier maps suggest that water displacement may occur from the so
      called "narrow" channel, resulting in binding of a new water molecule to the OEC,
      and thus provide new insights into the nature of rearrangements of water ligands
      along the catalytic cycle before O=O bond formation.

PMID- 29057332
TI  - Population attributable risks of neurobehavioral disorders due to low birth
      weight in US children.
AB  - BACKGROUND: The prevalence of low birth weight (LBW) and neurobehavioral
      disorders (N) has increased over the last three decades. However, it is unclear
      how many excess cases of ND can be attributed to LBW among U.S. children. The
      objectives of this study were to a) determine the association between LBW and ND
      including attention deficit/hyperactivity disorder (ADHD), autism spectrum
      disorder (ASD), behavior and conduct disorder (BCD) and learning disability (LD);
      and b) determine the population attributable risk (PAR) of these disorders due to
      LBW. METHODS: Study subjects were a nationally representative cross-sectional
      sample of 85,637 children ages 2 to 17 years old who participated in the 2011
      National Survey of Children's Health. Birth weight and ND were reported by
      parents. RESULTS: LBW accounted for 6.0% (95% confidence interval [CI] 2.3-10.4)
      of all ASD cases, 2.4% (CI 0.1-5.1) of BCD, and 6.8% (CI 4.8-9.0) of LD among the
      study population. There was not a significant association between LBW and ADHD.
      The percentages of these ND due to LBW were found to be higher among those who
      were pre-term and among ethnic minority groups. CONCLUSIONS: Based on our results
      and given that over 8% of U.S. children are born with LBW, with higher rates
      among minorities and preterm births, prospective planning for neurobehavioral
      services is warranted. Efforts to reduce ND in children align with national
      efforts to reduce LBW.

PMID- 29057333
TI  - A Magnetic Resonance Imaging-based approach to quantify radiation-induced normal
      tissue injuries applied to trismus in head and neck cancer.
AB  - BACKGROUND AND PURPOSE: In this study we investigated the ability of textures
      from T1-weighted MRI scans post-contrast (T1wpost) to identify the critical
      muscle(s) for radiation-induced trismus. MATERIALS AND METHODS: The study
      included ten cases (Trismus: >=Grade 1), and ten age-sex-tumor-location-and-stage
      matched controls treated with intensity-modulated radiotherapy to 70Gy@2.12Gy in
      2005-2009. Trismus status and T1wPost were conducted within one year post
      radiotherapy. For the masseter, lateral and medial pterygoids, and temporalis
      (M/LP/MP/T), 24 textures were extracted (Grey Level Co-Occurrence (GLCM),
      Histogram, and Shape). Univariate logistic regression with Bootstrapping (1000
      populations) was applied to compare the muscle mean dose (Dmean) and textures
      between cases and controls (ipsilateral muscles); candidate predictors were
      suggested by an average p<=0.20 across all Bootstrap populations. RESULTS: Dmean
      to M/LP/MP (p=0.03/0.14/0.09), one MP/T (p=0.12/0.17), and three M (p=0.14-0.19)
      textures were candidate predictors. Three of these textures were GLCM- and two
      Histogram textures with the former being generally higher and the latter lower
      for cases compared to controls. The Dmean to M and MP, and Haralick Correlation
      (GLCM) of MP presented with the best discriminative ability (area under the
      receiver-operating characteristic curve: 0.85, 0.77, and 0.78), and the
      correlation between Dmean and this texture was weak (Spearman's rank correlation
      coefficient: 0.26-0.27). CONCLUSIONS: Our exploratory study points towards an
      interplay between the dose to the masseter, and the medial pterygoid together
      with the local relationship between the mean MRI intensity relative to its
      variance of the medial pterygoid for radiation-induced trismus. This opens up for
      exploration of this interplay within the radiation-induced trismus etiology in
      the larger multi-institutional setting.

PMID- 29057334
TI  - Antouka Super(r) induced oxidative stress and reproductive toxicity in male
      Japanese quail (Coturnix coturnix japonica).
AB  - BACKGROUND: Antouka Super(r) (AS), a combination of insecticide (Pirimiphos
      methyl 16% and Permethrin 3%), is one of the most widely used pesticides in
      agriculture, public health, home and garden, with high potential for human and
      animal exposure. OBJECTIVE: The present study was undertaken to evaluate the
      effect of AS on the serum testosterone, oxidative stress biomarkers, testis
      histology and fertility of male Japanese quail. METHODS: Thirty-two (32) male
      Japanese quails twenty-eight (28) days were randomly divided into four groups: C0
      (control), T1, T2 and T3, exposed daily (gavage) to 0, 37.5, 56.25 and 75 mg of
      AS/kg body weight (b.w), respectively, for 49 consecutive days and were analysed
      for fertility. Control and experimental male quails were cohabited, for two days,
      with untreated female quails and sperm positive female quail were analysed for
      paternal-mediated toxicity. After completion of fertility studies quails were
      sacrificed and analysed for reproductive endpoints. RESULTS: There was a dose
      dependent decrease of the relative weight of testis, epididymis and vas deferens.
      Additionally, testis total proteins and serum testosterone levels were decreased
      in AS treated quails (p < 0.05). A decrease of sperm motility, viability and
      concentration per vas deferens, and an increase of sperm anomalies were recorded
      in AS exposed quails with respect to the controls. The embryonic and post
      embryonic mortality rate were significantly (p < 0.05) higher in group T3 (25.00
      +/- 3.40% and 31.66 +/- 10.22% respectively) than in control group (6.25 +/-
      3.98% and 9.54 +/- 3.72% respectively). The superoxide dismutase (SOD), total
      peroxidase (POD) and catalase activity (CAT) were significantly (p < 0.05) lower
      treated than control quails, while the level of malondialdehyde (MDA) was
      significantly (p < 0.05) higher in groups T1, T2 and T3 (13.00 +/- 0.96, 23.50 +/
      1.35 and 29.08 +/- 1.58 nmol/mg tissues respectively) compared to the control
      one (9.32 +/- 0.67nmol/mg tissues). Histopathological examination of the testes
      of AS treated quails revealed testicular lesions characterized by moderate to
      severe degenerative changes of seminiferous tubules, incomplete spermatogenesis
      and depletion in the germ layers of seminiferous tubules in which immature
      spermatozoa were hardly seen. CONCLUSION: From the above study, it can be
      inferred that AS (56.25 and 75) mg/kg b.w decrease body and relative organ
      weights and induces testicular lesions. Also, AS increases the level of MDA while
      it reduces the levels of enzymatic antioxidant biomarkers, serum testosterone and
      reproductive indices of intoxicated quails and their offspring. However, further
      work is needed to establish the genetic toxicology and immunohistochemistry of
      caspase-3 and claudin-1.

PMID- 29057335
TI  - Potential health and economic benefits of three locally grown nuts in Nigeria:
      implications for developing countries.
AB  - Malnutrition and lack of economic sustainability are major problems in developing
      countries. This study was conducted to evaluate and compare the nutrients'
      contents of three locally grown nuts in Nigeria (local groundnut, Kampala
      groundnut and breadnut) and highlight their health and economic potentials.
      Proximate analysis, chemical properties, minerals and fatty acids composition of
      the nuts were determined. The highest protein, crude fibre and carbohydrate
      contents were found in Kampala groundnut, local groundnut and breadnut
      respectively. Their sodium-potassium ratios were all less than 1.0 and their oils
      have mainly unsaturated fatty acids. Their acid values ranged between (2.41-6.34
      mgKOH/g) while the iodine values were between 36.0 and 93.0 I2 g/100 g. Analysis
      of the nuts and their oils indicated that they could help in solving malnutrition
      problem and also boost nations' economy. Encouraging their large scale production
      can enhance adequate nutrition and sustain industrial growth in developing
      countries.

PMID- 29057336
TI  - Evaluation of the stability of lyophilized loop-mediated isothermal amplification
      reagents for the detection of Coxiella burnetii.
AB  - Coxiella burnetii, the causative pathogen for Q fever, is an obligate
      intracellular bacterium and designated as a biosafety level 3 agent. Detection
      and quantification of the bacteria with conventional culturing methods is time
      consuming and poses significant health risks. Polymerase chain reaction (PCR)
      based assays have been developed for detecting C. burnetii and could provide
      rapid diagnosis. However, they require specialized equipment, including a cold
      chain for PCR reagents that maintains their stability during storage and
      transport. These requirements limit the advantage of PCR-based methods,
      especially in resource-limited areas. Previously, we had developed a lyophilized
      loop-mediated isothermal amplification (LAMP) assay to detect the presence of C.
      burnetii. To simplify and improve this assay, the reagents for the LAMP assay and
      the detecting reagent, SYBR green, were lyophilized together. The stability of
      the lyophilized reagents was evaluated by measuring changes in detection limit
      for plasmid DNA encoding a C. burnetii gene upon storage at 4  degrees C, 25 
      degrees C, or 37  degrees C. Our data indicate that the lyophilized reagents
      remain stable for 24 months when stored at 4  degrees C, 28 days at 25  degrees
      C, and 2 days at 37  degrees C. This improved LAMP assay can be easily performed
      in a simple water bath or heating block. The stability at ambient temperature,
      the simplicity of assay procedure, and the availability of low cost equipment
      make this method ideal for use in resource-limited settings where Q fever is
      endemic.

PMID- 29057337
TI  - The cosmic microwave background radiation power spectrum as a random bit
      generator for symmetric- and asymmetric-key cryptography.
AB  - In this note, the Cosmic Microwave Background (CMB) Radiation is shown to be
      capable of functioning as a Random Bit Generator, and constitutes an effectively
      infinite supply of truly random one-time pad values of arbitrary length. It is
      further argued that the CMB power spectrum potentially conforms to the FIPS 140-2
      standard. Additionally, its applicability to the generation of a (n * n) random
      key matrix for a Vernam cipher is established.

PMID- 29057338
TI  - Single anterior cervical discectomy and fusion (ACDF) using self- locking stand
      alone polyetheretherketone (PEEK) cage: evaluation of pain and health-related
      quality of life.
AB  - BACKGROUND: Anterior cervical discectomy and fusion (ACDF) constitutes the
      conventional treatment of cervical disc herniation due to degenerative disc
      disease (DDD). ACDF with plating presents a variety of complications
      postoperatively and stand-alone cages are thought to be a promising alternative.
      The aim of this study was firstly, to analyze prospectively collected data from a
      sample of patients treated with single ACDF using C-Plus self-locking stand-alone
      PEEK cage system, without the use of plates or screws, in order to evaluate pain
      levels of patients, utilizing Neck and Arm Pain scale as an expression of visual
      analogue scale (VAS). Secondly, we aimed to evaluate health-related quality of
      life, via the short-form 36 (SF-36) and Neck Disability Index (NDI). METHODS:
      Thirty-six patients (19 male and 17 female) with mean age 49.6+/-7 years old who
      underwent successful single ACDF using self-locking stand-alone PEEK cage for
      symptomatic cervical DDD were selected for the study. Neck and Arm pain, as well
      as SF-36 and NDI were estimated preoperatively and 1, 3, 6, and 12 months
      postoperatively. Patients underwent preoperative and postoperative clinical,
      neurological and radiological evaluation. RESULTS: The clinical and radiological
      outcomes were satisfactory after a minimum 1-year follow-up. All results were
      statistically important (P<0.05), excluding improvement in NDI measured between 6
      and 12 months. SF-36, Neck Pain, as well as Arm Pain featured gradual and
      constant improvement during follow-up, with best scores presenting at 12 months
      after surgery, while NDI reached its best at 6 months postoperatively.
      CONCLUSIONS: Generally, all scores showed improvement postoperatively during the
      different phases of the follow-up. Subsequently, ACDF using C-Plus cervical cage
      constitutes an effective method for cervical disc herniation treatment, in terms
      of postoperative improvement on pain levels and health-related quality of life
      and a safe alternative to the conventional method of treatment for cervical DDD.

PMID- 29057339
TI  - Composite PEEK/Carbon fiber implants can increase the effectiveness of
      radiotherapy in the management of spine tumors.
AB  - BACKGROUND: Combination of surgery and radiotherapy in the treatment of primary
      spine tumour can be indicated in some cases where a satisfactory oncological
      margin cannot be achieved. The presence of metal hardware has always limited post
      operative radiotherapy due to the scattering effects of ionizing radiation or
      particles. The use of a fixation system (including rods and screw) fully made in
      PEEK embedded Carbon fiber (CFR-PEEK) could make easier and more effective the
      post-operative radiotherapy as it is radiolucent and does not interfere with
      ionizing radiation and accelerated particles. METHODS: An ambispective study was
      performed on the first 22 consecutive primary tumor patients, who underwent
      spinal surgery including a composite CFR-PEEK fixation system. Oncologic surgery
      was palliative decompression and fixation in 3 cases; tumor excision in 15; en
      bloc resection in 4. The incidence of complications (intra- and postoperative),
      local control (LC) and local recurrence (LR), and changes in neurological status
      were considered. RESULTS: Only one intraoperative screw breakage occurred and one
      case of loosening of sacral screws were found at 12 months in one patient. No rod
      breakage, neither any screw/rod disconnection was found. Post-operative RT has
      been performed in 19 patients. The overall number of progression of the tumour or
      LR was 7. The actuarial rate of LR or progression of the tumour, calculated
      according to the Kaplan-Meier method, was 17.6% at 12 months. CONCLUSIONS: The
      CFR-PEEK fixation system is comparable to standard titanium system in term of
      intraoperative complications, stability at weight bearing and at functional
      recovery. Thanks to radiolucency CFR-PEEK stabilization devices are more suitable
      in patients eligible for RT: the absence of image artifacts together with
      significantly less dose perturbation improve the treatment accuracy. Moreover the
      radiolucency is useful in the follow-up of patients thus allowing early detection
      of LR.

PMID- 29057340
TI  - Lateral lumbar interbody fusion with unilateral pedicle screw fixation for the
      treatment of adjacent segment disease: a preliminary report.
AB  - BACKGROUND: To assess the clinical outcomes of 20 patients who underwent single
      level unilateral pedicle screw fixation following lateral lumbar interbody fusion
      (LLIF) for treatment of lumbar adjacent segment disease (ASD). METHODS:
      Demographic, comorbidity, clinical assessment, peri-operative, and complication
      data were assessed. Visual analog scale (VAS), Oswestry disability index (ODI),
      and short form-12 (SF-12) were used to assess clinical outcomes. Post-operative
      radiographs were assessed for subsidence, cage migration, and fusion. RESULTS:
      Average age of patients was 63.2+/-13.7 years (range, 41-86 years), with 8 males
      and 12 females. Recombinant human bone morphogenic protein-2 (rhBMP-2) was
      utilized in 18 LLIF cages (90%) and 12 posterolateral fusions (60%). Mean
      operation time was 214.1+/-47.2 minutes (range, 146-342 minutes), mean estimated
      blood loss of 187.5+/-90.1 cc (range, 50-400 cc). No patients received a blood
      transfusion. There were no intra-operative complications. Mean hospital length of
      stay was 4.4+/-1.7 days (range, 2-9 days). At final follow-up (mean: 13.0+/-12.7
      months after surgery), there was significant improvement in post-op VAS (P=0.006)
      score compared to pre-op, but not ODI (P=0.181), SF-12 PC (P=0.480), and SF-12 MC
      (P=0.937). Patients with >6 months of post-operative imaging (14/20, 70%)
      demonstrated successful fusion in 13 out of 14 cases (93%). There was grade 0
      subsidence of adjacent cranial vertebra in all cases (100%). There was grade 0
      subsidence of the adjacent caudal vertebra in 13 cases (93%) and grade 1
      subsidence in 1 case (7%). There was evidence of cage migration in 3 cases (21%).
      There were 4 patients (20%) who experienced transient neurological deficits that
      eventually resolved. Two patients required surgery for further ASD. CONCLUSIONS:
      In conclusion, this pilot study suggests that patients who undergo LLIF with
      unilateral pedicle screw fixation for treatment of ASD may have significantly
      reduced pain and favorable radiographic results. Further investigation in
      techniques for treatment of ASD is warranted.

PMID- 29057341
TI  - Early clinical and radiological results of unilateral posterior pedicle
      instrumentation through a Wiltse approach with lateral lumbar interbody fusion.
AB  - BACKGROUND: To assess the clinical outcomes of 44 patients who underwent single
      level lateral lumbar interbody fusion (LLIF) with unilateral pedicle screw
      instrumentation through a paramedian Wiltse approach. METHODS: Demographic,
      comorbidity, clinical assessment, peri-operative, and complication data were
      assessed. Visual analog scale (VAS), Oswestry disability index (ODI), and short
      form-12 (SF-12) were used to assess clinical outcomes. Post-operative plain
      radiographs were assessed for subsidence, cage migration, and fusion. RESULTS:
      Average age of patients at surgery was 60.8+/-10.6 years (range, 32-79 years),
      with 15 males and 29 females. Recombinant human bone morphogenic protein-2 (rhBMP
      2) was used in 32 cases (73%) and 13 posterolateral fusions (30%). Average
      duration of surgery was 195.2+/-36.9 minutes (range: 111-295 minutes), with an
      estimated blood loss of 159.3+/-90.8 cc (range, 50-500 cc). There were no intra
      operative complications. Average length of hospital stay was 4.2+/-2.5 days
      (range, 2-13 days). Four patients (9%) experienced neurological deficit, 2 of
      which resolved by 3-month follow-up and 2 of which improved but did not resolve
      by final follow-up at 11 and 16 months. There was significant improvement in VAS
      (P<0.001), ODI (P<0.001), and SF-12 physical component (P<0.001), but not for SF
      12 mental component (P=0.053). Patients with minimum 6 months radiographic follow
      up demonstrated successful fusion in 90% of cases (35/39), with 2 cases of grade
      1 (5%) subsidence of the adjacent cranial vertebra, and no cases higher than
      grade 0 subsidence of the adjacent caudal vertebra. CONCLUSIONS: Unilateral
      pedicle screw instrumentation following LLIF was associated with significant
      improvement in clinical outcomes and favorable radiographic outcomes.

PMID- 29057342
TI  - Effect of body mass index on patient outcomes of surgical intervention for the
      lumbar spine.
AB  - BACKGROUND: Conflicting findings exist on the effect of obesity on outcomes of
      lumbar spine surgery; results depend on the diagnosis studied, procedure
      evaluated, definition of obesity, and specific outcomes measured. The purpose of
      this retrospective cohort study is to examine the effect of increasing body mass
      index (BMI) on surgical-related, health-related, and long-term outcomes of lumbar
      spine surgery in a single representative patient sample. METHODS: Using a
      surgical registry from an integrated health care system, 8,049 instrumented
      lumbar spine cases were identified between 1/1/2009 and 09/30/2013. The sample
      was stratified into five BMI categories. Outcomes of interest included: (I)
      surgical-related factors and complications; (II) health-related complications;
      and (III) long-term complications. Mixed linear models, conditional logistic
      regressions, and survival analysis using a Cox regression model were conducted
      controlling for surgeon effects. Age, gender, diabetes status, smoking status,
      admitting diagnosis, and surgical approach were included as covariates. RESULTS:
      Every 5 kg/m2 increase in BMI was associated with a significant increase in
      surgical time (7.8 minutes), estimated blood loss (EBL) (36.5 mL), risk of deep
      infection (OR =1.7 times), and deep vein thrombosis (DVT) (OR =1.5). BMI was not
      associated with increased incidence of other intraoperative or health-related
      complications. Rate of re-operation was 1.1 times higher with every 5 kg/m2
      increase in BMI, but rate of re-operation due to adjacent segment disease (ASD)
      was not associated with BMI. CONCLUSIONS: Obesity had an adverse effect on
      certain surgical-related, health-related and long-term surgical outcomes. The
      magnitude of this effect increased with increasing levels of obesity, which
      increases the medical burden associated with obesity.

PMID- 29057343
TI  - The prevalence of undiagnosed pre-surgical cognitive impairment and its post
      surgical clinical impact in elderly patients undergoing surgery for adult spinal
      deformity.
AB  - BACKGROUND: Pre-existing cognitive impairment (CI) is emerging as a predictor of
      poor post-operative outcomes in elderly patients. Little is known about impaired
      preoperative cognition and outcomes after elective spine surgery in this patient
      population. The purpose of this study was to assess the prevalence of neuro CI in
      elderly patients undergoing deformity surgery and its impact on postoperative
      outcomes. METHODS: Elderly subjects undergoing elective spinal surgery for
      correction of adult degenerative scoliosis were enrolled in this study. Pre
      operative baseline cognition was assessed using the Saint Louis Mental Status
      (SLUMS) test. SLUMS consists of 11 questions, which can give a maximum of 30
      points. Mild CI was defined as a SLUMS score between 21-26 points, while severe
      CI was defined as a SLUMS score of <=20 points. Normal cognition was defined as a
      SLUMS score of >=27 points. Complication rates, duration of hospital stay, and 30
      day readmission rates were compared between patients with and without baseline
      CI. RESULTS: Eighty-two subjects were included in this study, with mean age of
      73.26+/-6.08 years. Fifty-seven patients (70%) had impaired cognition at
      baseline. The impaired cognition group had the following outcomes: increased
      incidence of one or more postoperative complications (39% vs. 20%), higher
      incidence of delirium (20% vs. 8%), and higher rate of discharge
      institutionalization at skilled nursing or acute rehab facilities (54% vs. 30%).
      The length of hospital stay and 30-day hospital readmission rates were similar
      between both cohorts (5.33 vs. 5.48 days and 12.28% vs. 12%, respectively).
      CONCLUSIONS: CI is highly prevalent in elderly patients undergoing surgery for
      adult degenerative scoliosis. Impaired cognition before surgery was associated
      with higher rates of post-operative delirium, complications, and discharge
      institutionalization. CI assessments should be considered in the pre-operative
      evaluations of elderly patients prior to surgery.

PMID- 29057344
TI  - Utilization of vertebroplasty and kyphoplasty procedures throughout the United
      States over a recent decade: an analysis of the Nationwide Inpatient Sample.
AB  - BACKGROUND: Given the increasing societal focus on health care utilization and
      value-based care, it is essential to understand the demographic and economic data
      surrounding percutaneous vertebral augmentation procedures performed in the
      United States. Double-blinded prospective randomized controlled trials have shown
      no benefit to the use of vertebroplasty over a sham procedure in the treatment of
      vertebral fractures. Contrastingly, kyphoplasty may be beneficial when
      appropriately indicated. METHODS: The National Inpatient Sample (NIS) database
      was queried for patients who underwent either kyphoplasty (ICD-9-CM 81.66) or
      vertebroplasty (ICD-9-CM 81.65) procedures between 2006 and 2014 across 44
      states. Demographic and economic data were obtained which included the annual
      number of surgeries, age, sex, insurance type, location, and frequency of routine
      discharge. The NIS database represents a 20% sample of discharges from U.S.
      hospitals, which is weighted to provide national estimates. RESULTS: In 2014, an
      estimated total number of 19,420 kyphoplasty and 6,130 vertebroplasty procedures
      were performed across the United States. The number of vertebroplasty procedures
      decreased 53% from 13,128 in 2008. Similarly, the number of kyphoplasty
      procedures decreased 17% from 23,320 in 2007. Based on payer, Medicare patients
      comprised 83% of those billed for kyphoplasty and vertebroplasty, and 75% of
      procedures were utilized in areas designated as "not low income". In 2014,
      patients in the South Atlantic region comprised 24% of vertebroplasty and 28% of
      kyphoplasty cases, far more than any other region. Additionally, kyphoplasty and
      vertebroplasty were more often performed in teaching facilities rather than
      community hospitals (60% and 67%, respectively). CONCLUSIONS: Since the
      publication of two double-blind, prospective randomized controlled trials showed
      no benefit of vertebroplasty over a sham procedure, there has been a significant
      decrease in both kyphoplasty and vertebroplasty procedures.

PMID- 29057345
TI  - Influence of psychosocial distress in the results of elective lumbar spine
      surgery.
AB  - BACKGROUND: Low back pain can be caused by several pathological entities and its
      perception can be altered by external factors, for example by some psychological
      and social factors. The objective of this study was to compare surgical outcomes
      in patients with or without psychosocial issues. METHODS: Single center,
      retrospective and comparative study. Patients with indication to elective lumbar
      spine surgery were screened for some psychosocial factors. As a result of the
      screening, patients were divided in two groups: mild psychosocial issues (green
      group) or moderate psychosocial issues (yellow group). The groups were compared
      using the following variables: demographic and clinical history, depression (HAD
      D), anxiety (HAD-A), pain levels [visual analogue scale (VAS)], disability
      [Oswestry disability index (ODI)] and quality of life [EuroQol 5D (EQ-5D)] at
      preop and 6-12 months follow-up. RESULTS: A total of 136 patients were included
      (51% female) in this study. The 62.5% were allocated at the green group, and
      37.5% in the yellow group. Similar pain levels were observed at preop, but the
      green group evolved with superior improvement in pain levels after surgery
      (P=0.003). In the ODI and EQ-5D scales, the green group had already shown lower
      clinical disability at preop (P=0.009 and P=0.003, respectively) and evolved with
      better outcomes at the final evaluation (P=0.049 and P=0.017). VAS, ODI and EQ-5D
      scores improved from baseline similarly in both groups. CONCLUSIONS: Presurgical
      screening identify the presence of psychological distress. Psychosocial factors
      are correlated with poorer clinical outcomes, both in the baseline and after the
      surgery. Despite the differences between found, even patients with mild
      psychosocial impairment can experience clinical improvement with surgery.

PMID- 29057347
TI  - Indirect pars repair for pediatric isthmic spondylolysis: a case series.
AB  - BACKGROUND: Isthmic spondylolysis (ISY) is a common cause of back pain in the
      pediatric population. Historically, non-operative treatments have had a very high
      success rate. The purpose of this study was to review the mid-term results of an
      indirect pars repair technique on reducing the visual analog score for pain
      (VAS), spondylolysis defect healing, complication rates and rates of return to
      pre-surgery activity level in pediatric patients who failed conservative care for
      ISY. METHODS: A retrospective review of all pediatric patients (<18 years old)
      treated surgically by one surgeon over a 5-year period was performed. Patients
      were treated with indirect pars repair utilizing pedicle screws and laminar hooks
      and local autograft. Preoperative VAS was compared to the final follow-up score,
      and return to activity was evaluated. Radiographs were reviewed to evaluate
      healing. RESULTS: Nine patients (6 females, 3 males) were treated surgically.
      Average age at the time of surgery was 15.4 years, (range, 13 to 17 years).
      Average length of final follow-up was 11.9 months (range, 6 to 24 months).
      Preoperative VAS averaged 5.6 points (range, 2 to 8 points) compared to final
      follow-up of 1.2 (range, 0 to 3). Definitive bony healing was noted in 7 of 9
      cases (77.8%) with at least 6 months follow-up. Eight of nine patients (88.9%)
      returned to preoperative competitive sports activity level. No complications were
      noted during the follow-up period. CONCLUSIONS: Pediatric patients treated
      surgically with indirect pars repair appear to achieve satisfactory mid-term
      outcomes. This technique appears safe, and has both a high healing rate and
      return to competitive athletics. Further study is needed to determine durability
      of this procedure.

PMID- 29057346
TI  - Corpectomy and expandable cage replacement versus third generation percutaneous
      augmentation system in case of vertebra plana: rationale and recommendations.
AB  - BACKGROUND: To evaluate the role of third generation percutaneous vertebral
      augmentation systems (Spine Jack(r)) as alternative to the corpectomies and
      expandable cages replacement (X-Core(r) Adjustable VBR System) in the treatment
      of vertebra plana (VP) as complication of the osteoporosis vertebral fracture
      (OVF). METHODS: Spine Jack(r) is a new device for mechanical kyphoplasty (MK). It
      is a titanium implant designed to restore the height of the vertebral body in
      OVF, primary or secondary bone tumors, or traumatic fractures. The X-Core(r)
      adjustable VBR System is a vertebral body replacement device indicated for use in
      the thoracolumbar spine (T1 to L5). The preoperative radiographic exams, computed
      tomography (CT), and magnetic resonance imaging (MRI) were performed in all
      cases. Clinical outcome measures included preoperative and postoperative Oswestry
      Disability Index (ODI), Visual Analog Scale pain score (VAS), neurologic
      examination, complications, estimated blood loss, and operating time.
      Postoperative radiographic evaluations were made at 1, 6, and 12 months. RESULTS:
      The anterior and middle column reconstruction by Spine Jack represents a valid
      alternative to the corpectomy in the patients affected by VP, especially in case
      elderly and/or high operative risk. In case of Spine Jack use, the correct
      indications must be respected: the hyperintense signal in STIR MRI sequences to
      the level of the fractures must be present. The eventual posterior spinal cord
      compression represents a relative contraindication. In case it would be superior
      to 1/3 and 2/3 respectively in case of fractures level above and below the spinal
      cord, a direct posterior spinal cord decompression must be performed.
      CONCLUSIONS: Avoiding the corpectomy, it is possible to reduce the operating time
      and the associated risks, as well as reducing blood loss.

PMID- 29057348
TI  - Navigation accuracy comparing non-covered frame and use of plastic sterile drapes
      to cover the reference frame in 3D acquisition.
AB  - BACKGROUND: Advancements in surgical navigation technology coupled with 3
      dimensional (3D) radiographic data have significantly enhanced the accuracy and
      efficiency of spinal fusion implant placement. Increased usage of such technology
      has led to rising concerns regarding maintenance of the sterile field, as
      makeshift drape systems are fraught with breaches thus presenting increased risk
      of surgical site infections (SSIs). A clinical need exists for a sterile draping
      solution with these techniques. Our objective was to quantify expected accuracy
      error associated with 2MM and 4MM thickness Sterile-Z Patient Drape(r) using
      Medtronic O-Arm(r) Surgical Imaging with StealthStation(r) S7(r) Navigation
      System. Camera distance to reference frame was investigated for contribution to
      accuracy error. METHODS: A testing jig was placed on the radiolucent table and
      the Medtronic passive reference frame was attached to jig. The StealthStation(r)
      S7(r) navigation camera was placed at various distances from testing jig and the
      geometry error of reference frame was captured for three different drape
      configurations: no drape, 2MM drape and 4MM drape. The O-Arm(r) gantry location
      and StealthStation(r) S7(r) camera position was maintained and seven 3D
      acquisitions for each of drape configurations were measured. Data was analyzed by
      a two-factor analysis of variance (ANOVA) and Bonferroni comparisons were used to
      assess the independent effects of camera angle and drape on accuracy error.
      RESULTS: Median (and maximum) measurement accuracy error was higher for the 2MM
      than for the 4MM drape for each camera distance. The most extreme error observed
      (4.6 mm) occurred when using the 2MM and the 'far' camera distance. The 4MM drape
      was found to induce an accuracy error of 0.11 mm (95% confidence interval, 0.06
      0.15; P<0.001) relative to the no drape testing, regardless of camera distance.
      Medium camera distance produced lower accuracy error than either the close
      (additional 0.08 mm error; 95% CI, 0-0.15; P=0.035) or far (additional 0.21mm
      error; 95% CI, 0.13-0.28; P<0.001) camera distances, regardless of whether a
      drape was used. CONCLUSIONS: In comparison to the 'no drape' condition, the
      accuracy error of 0.11 mm when using a 4MM film drape is minimal and clinically
      insignificant.

PMID- 29057349
TI  - Clinical evaluation of microendoscopy-assisted extreme lateral interbody fusion.
AB  - BACKGROUND: Extreme lateral interbody fusion (XLIF) has rapidly become a popular
      operative procedure for lumbar canal stenosis and scoliosis. This approach
      provides direct access to the lateral aspect of the disc with minimal disruption
      of spinal structures, including ligaments and muscles. However, it involves risk
      of injuries to the lumbar nerve plexus, segmental artery and intestinal tract
      because of the limited surgical field. This study aimed to clarify the benefit of
      using a microendoscope to prevent these injuries. METHODS: A total of 96
      consecutive patients treated by a single surgeon were retrospectively analyzed.
      The basic approach via the psoas muscle was performed in accordance with the
      conventional XLIF procedure. Operative manipulations, such as insertion of the
      shim, discectomy, endplate preparation and intervertebral spacer placement, were
      performed with the assistance of a microendoscope. Preoperative and postoperative
      neurological status were evaluated using the Japanese Orthopedic Association
      (JOA) scores and the Oswestry Disability Index (ODI). RESULTS: Eighty-four
      patients underwent surgery for a single vertebral level, nine patients underwent
      surgery for 2 levels and three patients underwent surgery for 3 levels (average,
      1.2 levels). The average age of patients was 61 years (range, 22-83 years); the
      mean follow-up period was 18 months (range, 3-36 months). Average preoperative
      and postoperative JOA scores were 11.9 and 15.6, with a mean recovery rate of
      33%. Average preoperative and postoperative ODI scores were 38.6 and 19.1. There
      were 3 (3.1%) complications: 2 end-plate fractures and 1 deep surgical site
      infection. There were no bowel perforations or vascular injuries. CONCLUSIONS:
      Microendoscopy assistance is one solution for severe visceral and vascular
      injuries related to XLIF.

PMID- 29057350
TI  - Impact of alcohol use on 30-day complication and readmission rates after elective
      spinal fusion (>=2 levels) for adult spine deformity: a single institutional
      study of 1,010 patients.
AB  - BACKGROUND: Alcohol use has been shown to affect surgical outcomes. However, it
      is unknown what effect alcohol use has on postoperative complications or
      readmission rates in spinal fusion surgery. The aim of this study is to determine
      the impact of preoperative alcohol use on 30-day readmission rates or the
      complications profile after adult elective spinal fusion for deformity correction
      (>=2 levels). METHODS: The medical records of 1,010 adult patients undergoing
      elective spinal fusion (>=2 levels) for spinal deformities at a major academic
      institution from 2005 to 2015 were reviewed. We identified 317 (31.4%) patients
      who had a history of alcohol prior to surgery and 693 (68.6%) patients who had no
      history of pre-operative alcohol consumption. The demographics, comorbidities,
      intra- and 30-day post-operative complication and readmission rates were
      collected for each patient. The primary outcome investigated in this study was
      the rate of 30-day readmissions and postoperative complication rates. RESULTS:
      Baseline characteristics were similar between both cohorts. Intraoperative
      variables and the immediate postoperative complications profile were mostly
      similar between both cohorts. Overall, there was no significant difference
      between the 30-day readmission rates or complications profile between the two
      cohorts. CONCLUSIONS: Our study suggests there is no significant difference in 30
      day readmission or complication rates among adult patients with or without
      preoperative alcohol use undergoing elective correction of spinal deformities.

PMID- 29057351
TI  - Versatility of sub-occipital approach for foramen magnum meningiomas: a single
      centre experience.
AB  - BACKGROUND: Foramen magnum meningiomas (FMM) represent a challenge for
      neurosurgeons. Multiple surgical strategies have been reported to treat these
      lesions in their variable location. Contemporary technical innovations allow the
      utilization of common sub-occipital craniotomy to treat ventrally, ventro
      laterally and dorsally located FMMs. We present our technique and experience.
      METHODS: From November 2004 to November 2015, we treated 14 patients with FMM at
      the Department of Neurosurgery of the Santa Maria delle Grazie Hospital in
      Pozzuoli, Naples, Italy. There were 10 females and 4 males, with a mean age of
      64.5 years (range, 55-77 years). All patients had high field magnetic resonance
      imaging (MRI) with contrast enhancement preoperatively, which led to the
      radiological diagnosis. A sub-occipital craniotomy was performed in all patients
      as well as the removal of the posterior arch of C1. Partial removal of C2 was
      necessary in 2 patients. Neck pain was the most common symptom of presentation.
      Paraparesis was present in patients in 3 patients. Upper limbs dysesthesia or
      pain existed in 3 cases. RESULTS: Thirty days after surgery neck pain and
      dysesthesia decreased in all patients affected. Neurological improvement was
      observed in 2 patients affected by weakness in lower limbs at 6 months follow up.
      Paraparesis was unchanged in 1 patient. Two patients presented transient
      worsening after surgery. Transient dysphagia occurred in one case and
      postoperative hemorrhage with subsequent surgery in another patient. We had no
      postoperative mortality. CONCLUSIONS: FMM surgery should be tailored to the
      lesion at hand as in most instances it is possible to avoid the use of extensive
      skull base approaches.

PMID- 29057352
TI  - Morphometric anatomy of the lumbar sympathetic trunk with respect to the
      anterolateral approach to lumbar interbody fusion: a cadaver study.
AB  - BACKGROUND: An approach to lateral lumbar interbody fusion (LLIF) utilizing an
      oblique corridor anterior to the psoas muscle was first described by Mayer in
      1997 and subsequently by other authors. The only consistent structure of note in
      this corridor is the lumbar sympathetic trunk (LST), which at times must be
      mobilized in order to perform a discectomy and interbody fusion, thereby placing
      the LST at risk. This study was designed to describe the morphometric anatomy of
      the LST in relation to surgically relevant landmarks for the anterolateral
      approach to the lumbar spine at L3/L4 to L5/S1. METHODS: Twenty-four embalmed
      cadavers (13 males, 11 females, age range, 50-89) were dissected to expose the
      LST. Bilateral measurements were recorded using a calliper under direct
      visualization, using the midsagittal plane of the lumbar spine as the reference
      landmark. The points were then marked with radio-opaque needles, and 14 cadavers
      were scanned with CT to validate the measurements. RESULTS: Of 48 LSTs, there was
      minimal difference in the direction of its course between sides; 14/24 specimens
      had concordant directions. The majority (n=28) had a medial to lateral
      cephalocaudal course. If osteophytes were present at the L4/L5 level, the
      majority of LSTs (n=7, of 8) were displaced lateral to the osteophyte. At the
      L5/S1 level, half of the cases with osteophytes (n=3, of 6) stretched the LST
      over the top of the osteophyte. The LST was adherent to the L4/L5 disc space
      bilaterally in 93% of cases. CONCLUSIONS: With the development of lumbar fusion
      techniques which utilize an oblique corridor and the retraction of psoas muscle,
      LST has become an important neural structure to define, protect and mobilize. In
      our morphometric analysis of 24 specimens, the position has been identified and
      quantified, and this paper notes variations, particularly distortions caused by
      degenerative processes. In this study, the LST ran in a medial to lateral
      direction from L3 to S1, and osteophytes typically displace and adhere to the
      LST.

PMID- 29057353
TI  - The Manubriotomy is a safe option for the anterior approach to the cervico
      thoracic junction.

PMID- 29057354
TI  - L5/S1 anterior lumbar interbody fusion technique.

PMID- 29057355
TI  - Systematic review of 3D printing in spinal surgery: the current state of play.
AB  - Three-dimensional printing (3DP), also known as "Additive Manufacturing", is a
      rapidly growing industry, particularly in the area of spinal surgery. Given the
      complex anatomy of the spine and delicate nature of surrounding structures, 3DP
      has the potential to aid surgical planning and procedural accuracy. We perform a
      systematic review of current literature on the applications of 3DP in spinal
      surgery. Six electronic databases were searched for original published studies
      reporting cases or outcomes for 3DP surgical models, guides or implants for
      spinal surgery. The findings of these studies were synthesized and summarized.
      These searches returned a combined 2,411 articles. Of these, 54 were included in
      this review. 3DP is currently used for surgical planning, intra-operative
      surgical guides, customised prostheses as well as "Off-the-Shelf" implants. The
      technology has the potential for enhanced implant properties, as well as
      decreased surgical time and better patient outcomes. The majority of the data
      thus far is from low-quality studies with inherent biases linked with the
      excitement of a new field. As the body of literature continues to expand, larger
      scale studies to evaluate advantages and disadvantages, and longer-term follow up
      will enhance our knowledge of the effect 3DP has in spinal surgery. In addition,
      issues such as financial impact, time to design and print, materials selection
      and bio-printing will evolve as this rapidly expanding field matures.

PMID- 29057357
TI  - Lumbar total disc replacement: does it still need further follow-up?

PMID- 29057358
TI  - CT guided radiofrequency ablation of the cervical medial branch using a lateral
      approach in the supine patient.

PMID- 29057356
TI  - Anterior cervical spine surgery-associated complications in a retrospective case
      control study.
AB  - Anterior cervical spine procedures have been associated with satisfactory
      outcomes. However, the occurrence of troublesome complications, although
      uncommon, needs to be taken into consideration. The purpose of our study was to
      assess the actual incidence of anterior cervical spine procedure-associated
      complications and identify any predisposing factors. A total of 114 patients
      undergoing anterior cervical procedures over a 6-year period were included in our
      retrospective, case-control study. The diagnosis was cervical radiculopathy,
      and/or myelopathy due to degenerative disc disease, cervical spondylosis, or
      traumatic cervical spine injury. All our participants underwent surgical
      treatment, and complications were recorded. The most commonly performed procedure
      (79%) was anterior cervical discectomy and fusion (ACDF). Fourteen patients
      (12.3%) underwent anterior cervical corpectomy and interbody fusion, seven (6.1%)
      ACDF with plating, two (1.7%) odontoid screw fixation, and one anterior removal
      of osteophytes for severe Forestier's disease. Mean follow-up time was 42.5
      months (range, 6-78 months). The overall complication rate was 13.2%.
      Specifically, we encountered adjacent intervertebral disc degeneration in 2.7% of
      our cases, dysphagia in 1.7%, postoperative soft tissue swelling and hematoma in
      1.7%, and dural penetration in 1.7%. Additionally, esophageal perforation was
      observed in 0.9%, aggravation of preexisting myelopathy in 0.9%, symptomatic
      recurrent laryngeal nerve palsy in 0.9%, mechanical failure in 0.9%, and
      superficial wound infection in 0.9%. In the vast majority anterior cervical spine
      surgery-associated complications are minor, requiring no further intervention.
      Awareness, early recognition, and appropriate management, are of paramount
      importance for improving the patients' overall functional outcome.

PMID- 29057359
TI  - Spinal metastases of two different grade oligodendrogliomas: a case report and
      review of literature.
AB  - Oligodendrogliomas (OGD) are glial tumors, together with mixed oligoastrocytoma
      constituting 5-20% of all gliomas, which occur predominantly in younger
      populations and are managed with surgery and chemotherapy with good long-term
      prognosis after treatment and additionally present with low rates of metastases.
      We present the case of a 46-year-old patient with intracranial right frontal
      subcortical OGD [World Health Organisation (WHO) grade II] managed at the
      Neurosurgery Department in Foscal Clinic, Floridablanca, Colombia. Two years
      after brain surgery the patient presents with neurological symptomatology
      suggestive of spinal cord compression and is found to have a neoplastic lesion
      with extra medullary compressive strength on the conus medullary and wrapping all
      of the roots with the final report of pathology and immunohistochemistry
      indicating: OGD (WHO grade III), this lesion was the only one found, the brain
      studies shows any residual tumor or recurrence in the primary tumor site.

PMID- 29057360
TI  - Surgery or not? A case of ventriculus terminalis in an adult patient.
AB  - The ventriculus terminalis (VT) is an intramedullary cavity containing
      cerebrospinal fluid (CSF), usually located at the conus, and represents an
      unsuccessful regression of a normal embryological phase of the development of the
      neural tube. Symptoms are not univocal and may vary from aspecific signs to
      sphincter dysfunctions and focal neurological deficits. The correct management of
      this condition is still an object of debate due to its rarity and its
      unpredictable behaviour in adult patients. Two different studies have proposed a
      distinction for patients with cystic dilatation of VT based on their symptoms,
      suggesting that only those patients with neurological deficits clearly related to
      the terminal ventricle could benefit from surgery. We describe a case of an adult
      patient with a progressive dilatation of a diagnosed VT that we treated
      surgically. A management flowchart for this condition is also proposed based on
      our experience and a review of the literature.

PMID- 29057361
TI  - Hypoglossal nerve paresis secondary to anterior approach of upper cervical spine
      followed by spontaneous recovery.
AB  - We describe an exceptional complication of cervical spine surgery in a 63-year
      old male. He suffered the impact of a beam to the top of his head. During
      evaluation in the emergency room he reported intense neck pain with no other
      neurological symptoms or findings on physical examination. Spine computed
      tomography (CT) showed C3 vertebral body fracture that required surgical
      stabilization. A right side anterior approach to upper cervical spine with C3
      corpectomy and placement of iliac bone autograft was performed. After surgery the
      patient presented dysphagia, dysarthria and limitation tongue mobility to the
      right side. These findings were consistent with hypoglossal neuropraxia probably
      related to soft tissue traction generated by the upper part of the self-retaining
      retractor. After discharge the patient experienced spontaneous improvement of
      hypoglossal paresis.

PMID- 29057362
TI  - Recurrent granular cell tumor: a case report and review of literature.
AB  - Granular cell tumors (GCTs) in the spine are uncommon. They are mostly located in
      the intradural extramedullary space and rarely, in an intramedullary (IM)
      location. Complete resection is the treatment of choice. Recurrences are rare in
      intradural-intramedullary (IDEM) GCTs. Recurrent and incompletely excised cases
      are subjected to adjuvant radiation therapy. We report such a recurrence in a 13
      year-old girl who was re-operated and subjected to radiotherapy.

PMID- 29057363
TI  - Congenital malformed posterior arch of atlas with fusion defect: a case of
      developmental canal stenosis causing cervical myelopathy.
AB  - Congenital anomalies of the posterior arch of the atlas (PAA) are usually
      asymptomatic and diagnosed incidentally. Very rarely, they present with cervical
      myelopathy, usually being associated with partial aplasia or agenesis of PAA. We
      describe a 44-year-old lady with cervical myelopathy secondary to a malformed PAA
      with developmental atlas-level spinal stenosis and a congenital posterior fusion
      defect with persistent midline cleft showing significant non-osseous fibro
      cartilaginous hypertrophy, causing critical cord compression. Spinal
      decompression by en-bloc wide excision of anomalous arch with occipito-cervical
      fusion was performed. Post-operatively, the patient's neurology improved
      gradually over 12 months, with radicular symptoms being the earliest and gait
      disturbance being the last symptom to resolve. At 24 months, she was asymptomatic
      with imaging showing good spinal cord decompression at the level of atlas.
      Developmental atlas stenosis with hypertrophic posterior arch fusion defect is an
      unusual cause of cervical myelopathy, which can be effectively treated with
      decompression with/without stabilization. Being aware of such an entity can avoid
      diagnostic dilemma and facilitate prognostication of outcomes, accurate surgical
      planning in the stenotic segment thereby ensuring effective management of these
      patients.

PMID- 29057364
TI  - PEMLIF-a tale of two stories.
AB  - Intervertebral disc prolapse is a common cause of both acute and chronic low back
      pain. This can result in differential grades of motor and sensory disturbances in
      lower limbs and even cauda equina syndrome (CES). The neurological manifestations
      are a result of compression of the spinal cord and roots ventrally in the spinal
      canal due to the prolapsed disc. However, neurologic deficits owing to
      compression of the spinal cord dorsally as a result of migration of sequestrated
      disc fragments are very rare. We present two different cases of back pain with
      severe neurologic deficit referred to us within a short span of one month. Among
      them, one had long standing history of back pain while other had none. Both
      patients were investigated and found to have a sequestrated disc fragment which
      had dorsally migrated to the epidural space and was causing severe compression of
      the spinal cord. They underwent laminectomy and removal of the sequestrated
      fragment. However, they were only partially relieved of their motor and bladder
      weakness. We present our cases to highlight this rare form of lumbar epidural
      intervertebral disc migration, as well as enumerate the diagnostic challenges and
      discuss the differential diagnosis and treatment.

PMID- 29057365
TI  - A rare case of intramedullary solitary juvenile xanthogranuloma of the lumbar
      spine in the adult: a case report.
AB  - Solitary juvenile xanthogranuloma (SJX) of the spine is an extremely rare
      proliferative histiocytic disorder with only few cases reported in literature. We
      present the first case of intramedullary spinal SJX. A 22-year-old male presented
      with a nine-month history of progressively worsening sphincteric disturbances and
      saddle hypoesthesia. Magnetic resonance imaging showed an intra-axial lesion
      located in the conus medullaris; T1 hypointense, T2 iso-hyperintense and
      uniformly enhancing after contrast administration. The lesion was removed through
      a T12-L1 laminectomy and a median myelotomy with neurophysiological monitoring.
      Histological examination and immunohistochemical testing confirmed the diagnosis
      of SJX. Due to the intramedullary localization and the absence of a clear
      cleavage plane, radical removal was not possible. The tumor subsequently recurred
      and new surgical procedures were necessary followed by adjuvant radiotherapy.
      Patient made good neurological recovery. Three years after the latest treatment,
      MRI showed no recurrence. In accordance with the literature, the treatment of
      choice for SJX its radical removal, or subtotal removal followed by adjuvant
      radiotherapy.

PMID- 29057366
TI  - Spinal tumour: primary cervical extradural meningioma at an unusual location.
AB  - Extradural spinal meningiomas are extremely rare, more so in the cervical region.
      A purely extradural location as reported in this paper is quite exceptional. The
      authors report a case of extradural meningioma in a 50-year-old male located in
      the cervical spine that was surgically treated with the provisional diagnosis of
      a neurofibroma. Histopathological diagnosis of meningothelial meningioma was made
      with the routine hematoxylin and eosin (HE) stain. The origin, clinical course,
      radiological features, pathological findings with the differential diagnosis and
      surgical treatment are discussed based on a review of the literature. An
      extradural spinal meningioma, an extremely rare entity, is still a diagnostic
      dilemma on radiology as the radiologic findings overlap with many other common
      extradural spinal masses.

PMID- 29057367
TI  - An unusual case of intradural intramedullary dorsal bronchogenic cyst in spine.
AB  - Bronchogenic cysts are congenital malformations derived from anomalous budding of
      the embryonic foregut. Intraspinal bronchogenic cysts are extremely rare and most
      of them are extramedullary. There has been only one case of intramedullary spinal
      bronchogenic cyst reported. We present an 18-year-old male patient with spastic
      paraparesis and bowel and bladder involvement. MRI revealed a 2 cm diameter
      intradural and intramedullary lesion at D2-D3 level which was hyperintense on T1
      and hypointense on T2 imaging. Histopathological examination after surgical
      excision of the lesion revealed a bronchogenic cyst. To our knowledge this is the
      first case reporting an intramedullary bronchogenic cyst at the upper dorsal
      level and overall second reported case of intramedullary spinal bronchogenic
      cyst.

PMID- 29057368
TI  - Intervention development for the indicated prevention of depression in later
      life: the "DIL" protocol in Goa, India.
AB  - Because depression is a major source of the global burden of illness- related
      disability, developing effective strategies for reducing its incidence is an
      important public health priority, especially in low-income countries, where
      resources for treating depression are scarce. We describe in this report an
      intervention development project, funded by the US National Institute of Mental
      Health, to address "indicated" prevention of depression in older adults attending
      rural and urban primary care clinics in Goa, India. Specifically, participants in
      the "DIL" ("Depression in Later Life") trial were older adults living with mild,
      subsyndromal symptoms of depression and anxiety and thus at substantial risk for
      transitioning to fully syndromal major depression and anxiety disorders. Building
      upon the MANAS treatment trial ("Promoting Mental Health") led by Patel et al in
      the same locale, we present here lessons learned in the development and
      implementation of a protocol utilizing lay health counsellors (LHCs) who deliver
      a multi-component depression prevention intervention organized conceptually
      around Problem Solving Therapy for Primary Care (PST), with additional components
      addressing brief behavioural treatment of sleep disturbances such as insomnia,
      meeting basic social casework needs, and education in self- management of
      prevalent comorbid chronic diseases, such as diabetes mellitus. To our knowledge,
      DIL is the first randomized clinical trial addressing the prevention of
      depressive disorders ever conducted in a low- or middle-income country.

PMID- 29057369
TI  - Internal Consistency of Functional Magnetic Resonance Imaging and
      Electroencephalography Measures of Reward in Late Childhood and Early
      Adolescence.
AB  - BACKGROUND: Abnormal neural response to reward is increasingly thought to
      function as a biological correlate of emerging psychopathology during
      adolescence. However, this view assumes such responses have good psychometric
      properties-especially internal consistency-an assumption that is rarely tested.
      METHODS: Internal consistency (i.e., spilt-half reliability) was calculated for
      event-related potentials (ERPs) and Blood Oxygen Level Dependent (BOLD) responses
      to monetary gain and loss feedback from the same sample of 8-14 year-old females
      (n=177). Internal consistency for ERPs (i.e. feedback negativity) and BOLD
      responses within the ventral striatum and medial/lateral prefrontal cortex to
      gain, loss, difference scores (gain-loss), and residual scores (gain controlling
      for loss) were compared. Moderation analyses were conducted to investigate
      whether internal consistency differed by age. RESULTS: ERP and BOLD responses to
      gain and loss feedback showed high internal consistency in all regions (Spearman
      Brown Coefficients (SB) >= 0.70). When considering difference and residual
      scores, however, responses showed lower internal consistency (SBs <= 0.50), with
      particularly low internal consistency for subtraction-based scores (SB <= 0.36).
      Age was not a significant moderator of split-half relationships, indicating
      similar internal consistency across late childhood to early adolescence.
      CONCLUSIONS: Within the same subjects, high internal consistency was observed for
      both ERP and fMRI measures of response to gains and losses, which did not vary as
      a function of age. Moreover, excellent psychometric properties were evident even
      within the first half of the experiment. Difference scores were characterized by
      lower internal consistency, although regression-based approaches outperformed
      subtraction-based difference scores.

PMID- 29057371
TI  - Dysflective cones: Visual function and cone reflectivity in long-term follow-up
      of acute bilateral foveolitis.
AB  - PURPOSE: Confocal adaptive optics scanning laser ophthalmoscope (AOSLO) images
      provide a sensitive measure of cone structure. However, the relationship between
      structural findings of diminished cone reflectivity and visual function is
      unclear. We used fundus-referenced testing to evaluate visual function in regions
      of apparent cone loss identified using confocal AOSLO images. METHODS: A patient
      diagnosed with acute bilateral foveolitis had spectral-domain optical coherence
      tomography (SD-OCT) (Spectralis HRA + OCT system [Heidelberg Engineering, Vista,
      CA, USA]) images indicating focal loss of the inner segment-outer segment
      junction band with an intact, but hyper-reflective, external limiting membrane.
      Five years after symptom onset, visual acuity had improved from 20/80 to 20/25,
      but the retinal appearance remained unchanged compared to 3 months after symptoms
      began. We performed structural assessments using SD-OCT, directional OCT (non
      standard use of a prototype on loan from Carl Zeiss Meditec) and AOSLO (custom
      built system). We also administered fundus-referenced functional tests in the
      region of apparent cone loss, including analysis of preferred retinal locus
      (PRL), AOSLO acuity, and microperimetry with tracking SLO (TSLO) (prototype
      system). To determine AOSLO-corrected visual acuity, the scanning laser was
      modulated with a tumbling E consistent with 20/30 visual acuity. Visual
      sensitivity was assessed in and around the lesion using TSLO microperimetry.
      Complete eye examination, including standard measures of best-corrected visual
      acuity, visual field tests, color fundus photos, and fundus auto-fluorescence
      were also performed. RESULTS: Despite a lack of visible cone profiles in the
      foveal lesion, fundus-referenced vision testing demonstrated visual function
      within the lesion consistent with cone function. The PRL was within the lesion of
      apparent cone loss at the fovea. AOSLO visual acuity tests were abnormal, but
      measurable: for trials in which the stimulus remained completely within the
      lesion, the subject got 48% correct, compared to 78% correct when the stimulus
      was outside the lesion. TSLO microperimetry revealed reduced, but detectible,
      sensitivity thresholds within the lesion. CONCLUSIONS AND IMPORTANCE: Fundus
      referenced visual testing proved useful to identify functional cones despite
      apparent photoreceptor loss identified using AOSLO and SD-OCT. While AOSLO and SD
      OCT appear to be sensitive for the detection of abnormal or absent
      photoreceptors, changes in photoreceptors that are identified with these imaging
      tools do not correlate completely with visual function in every patient. Fundus
      referenced vision testing is a useful tool to indicate the presence of cones that
      may be amenable to recovery or response to experimental therapies despite not
      being visible on confocal AOSLO or SD-OCT images.

PMID- 29057370
TI  - Conditional Human Immunodeficiency Virus Transactivator of Transcription Protein
      Expression Induces Depression-like Effects and Oxidative Stress.
AB  - BACKGROUND: The prevalence of major depression in those with HIV/AIDS is
      substantially higher than in the general population. Mechanisms underlying this
      comorbidity are poorly understood. HIV-transactivator of transcription (Tat)
      protein, produced and excreted by HIV, could be involved. We determined whether
      conditional Tat protein expression in mice is sufficient to induce depression
      like behaviors and oxidative stress. Further, as oxidative stress is associated
      with depression, we determined whether decreasing or increasing oxidative stress
      by administering methylsulfonylmethane (MSM) or diethylmaleate (DEM),
      respectively, altered depression-like behavior. METHODS: GT-tg bigenic mice
      received intraperitoneal saline or doxycycline (Dox, 25-100 mg/kg/day) to induce
      Tat expression. G-tg mice, which do not express Tat protein, also received Dox.
      Depression-like behavior was assessed with the tail suspension test (TST) and the
      two-bottle saccharin/water consumption task. Reactive oxygen/nitrogen species
      (ROS/RNS) were assessed ex vivo. Medial frontal cortex (MFC) oxidative stress and
      temperature were measured in vivo with 9.4-Tesla proton magnetic resonance
      spectroscopy (MRS). RESULTS: Tat expression increased TST immobility time in an
      exposure-dependent manner and reduced saccharin consumption. MSM decreased
      immobility time while DEM increased it in saline-treated GT-tg mice. Tat and MSM
      behavioral effects persisted for 28 days. Tat and DEM increased while MSM
      decreased ROS/RNS levels. Tat expression increased MFC glutathione levels and
      temperature. CONCLUSIONS: Tat expression induced rapid and enduring depression
      like behaviors and oxidative stress. Increasing/decreasing oxidative stress
      increased/decreased, respectively, depression-like behavior. Thus, Tat produced
      by HIV may contribute to the high depression prevalence among those with HIV.
      Further, mitigation of oxidative stress could reduce depression severity.

PMID- 29057372
TI  - Do the psychological effects of vagus nerve stimulation partially mediate vagal
      pain modulation?
AB  - There is preclinical and clinical evidence that vagus nerve stimulation modulates
      both pain and mood state. Mechanistic studies show brainstem circuitry involved
      in pain modulation by vagus nerve stimulation, but little is known about possible
      indirect descending effects of altered mood state on pain perception. This
      possibility is important, since previous studies have shown that mood state
      affects pain, particularly the affective dimension (pain unpleasantness). To
      date, human studies investigating the effects of vagus nerve stimulation on pain
      perception have not reliably measured psychological factors to determine their
      role in altered pain perception elicited by vagus nerve stimulation. Thus, it
      remains unclear how much of a role psychological factors play in vagal pain
      modulation. Here, we present a rationale for including psychological measures in
      future vagus nerve stimulation studies on pain.

PMID- 29057373
TI  - Biokinetics of Nanomaterials: the Role of Biopersistence.
AB  - Nanotechnology risk management strategies and environmental regulations continue
      to rely on hazard and exposure assessment protocols developed for bulk materials,
      including larger size particles, while commercial application of nanomaterials
      (NMs) increases. In order to support and corroborate risk assessment of NMs for
      workers, consumers, and the environment it is crucial to establish the impact of
      biopersistence of NMs at realistic doses. In the future, such data will allow a
      more refined future categorization of NMs. Despite many experiments on NM
      characterization and numerous in vitro and in vivo studies, several questions
      remain unanswered including the influence of biopersistence on the toxicity of
      NMs. It is unclear which criteria to apply to characterize a NM as biopersistent.
      Detection and quantification of NMs, especially determination of their state,
      i.e., dissolution, aggregation, and agglomeration within biological matrices and
      other environments are still challenging tasks; moreover mechanisms of
      nanoparticle (NP) translocation and persistence remain critical gaps. This review
      summarizes the current understanding of NM biokinetics focusing on determinants
      of biopersistence. Thorough particle characterization in different exposure
      scenarios and biological matrices requires use of suitable analytical methods and
      is a prerequisite to understand biopersistence and for the development of
      appropriate dosimetry. Analytical tools that potentially can facilitate
      elucidation of key NM characteristics, such as ion beam microscopy (IBM) and time
      of-flight secondary ion mass spectrometry (ToF-SIMS), are discussed in relation
      to their potential to advance the understanding of biopersistent NM kinetics. We
      conclude that a major requirement for future nanosafety research is the
      development and application of analytical tools to characterize NPs in different
      exposure scenarios and biological matrices.

PMID- 29057374
TI  - A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban
      Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.
AB  - Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in
      cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation.
      PLN hypophosphorylation is a common molecular feature in failing heart. The
      current study provided evidence at molecular, cellular and whole heart levels to
      implicate a sarcolemma membrane targeted protein phosphatase, PP2Ce, as a
      specific and potent PLN phosphatase. PP2Ce expression was elevated in failing
      human heart and induced acutely at protein level by beta -adrenergic stimulation
      or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted
      beta-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore,
      PP2Ce is a new regulator for cardiac function and pathogenesis.

PMID- 29057376
TI  - P2Y12 Receptor Function and Response to Cangrelor in Neonates With Cyanotic
      Congenital Heart Disease.
AB  - Shunt thrombosis remains a major cause of morbidity and mortality, especially
      during the initial palliation for single-ventricle physiology. The authors
      present evidence that the P2Y12 inhibitor cangrelor may fill a therapeutic void
      in thromboprophylaxis. They base this theory on results showing that platelets
      from neonatal patients with cyanotic congenital heart disease have a robust
      response to adenosine diphosphate and are amenable to P2Y12 inhibition with
      cangrelor. Unique to this study was their ability to establish drug efficacy in
      an avatar mouse model that permits the in vivo evaluation of human platelet
      mediated thrombus formation illustrating that this P2Y12 inhibitor yields the
      intended biological response.

PMID- 29057375
TI  - Designing Acellular Injectable Biomaterial Therapeutics for Treating Myocardial
      Infarction and Peripheral Artery Disease.
AB  - As the number of global deaths attributed to cardiovascular disease continues to
      rise, viable treatments for cardiovascular events such as myocardial infarction
      (MI) or conditions like peripheral artery disease (PAD) are critical. Recent
      studies investigating injectable biomaterials have shown promise in promoting
      tissue regeneration and functional improvement, and in some cases, incorporating
      other therapeutics further augments the beneficial effects of these biomaterials.
      In this review, we aim to emphasize the advantages of acellular injectable
      biomaterial-based therapies, specifically material-alone approaches or delivery
      of acellular biologics, in regards to manufacturability and the capacity of these
      biomaterials to regenerate or repair diseased tissue. We will focus on design
      parameters and mechanisms that maximize therapeutic efficacy, particularly,
      improved functional perfusion and neovascularization regarding PAD and improved
      cardiac function and reduced negative left ventricular (LV) remodeling post-MI.
      We will then discuss the rationale and challenges of designing new injectable
      biomaterial-based therapies for the clinic.

PMID- 29057377
TI  - Cellular network perturbations by disease-associated variants.
AB  - Genetic and genome-wide association studies (GWAS) have identified a myriad of
      human disease-associated genomic variants. However, these studies do not reveal
      the mechanisms by which these variants perturb cellular networks, a necessary
      step to intervene and improve disease outcomes. This has been challenging because
      multiple variants are present in haplotype blocks, thereby confounding the
      identification of causal variants, and because most reside in noncoding regions.
      Here, we review recent advances in the identification of functional variants and
      gene-variant associations. In addition, we examine approaches used to study
      perturbations in protein-protein and protein-DNA interactions associated with
      disease, and discuss how these perturbations affect cellular networks.

PMID- 29057379
TI  - The Associations between Yelp Online Reviews and Vape Shops Closing or Remaining
      Open One Year Later.
AB  - INTRODUCTION: Vape shops are popular brick-and-mortar stores that sell e
      cigarette products but are not understood well. Previous analysis of Yelp reviews
      of vape shops located in various ethnic neighborhoods in Los Angeles, California
      in 2014 identified characteristics of vape shop as delineated by consumers. In
      this study, we assessed the associations between these characteristics and vape
      shops going out of business in 2015. METHODS: Content analysis of Yelp reviews of
      72 vape shops in 2014 identified 1) general characteristics of the
      reviews/reviewers, 2) vape shop, staff, and marketing attributes, 3) physical
      environment, and 4) health claims. In 2015, in-person visits confirmed that 22%
      of these vape shops closed permanently. We analyzed whether
      characteristics/attributes identified in 2014 associated with stores remaining
      open (n = 56) or permanently closing (n = 16) in 2015. RESULTS: Univariate
      findings showed that open vape shops relative to closed shops had greater 1)
      number of reviews, 2) rebuilds/fixings, 3) ratings of staff attributes as
      "helpful/patient/respectful," and 4) report of the physical environment as "bar
      type." CONCLUSIONS: Bar type vape shops and those with rebuilding/fixing
      capabilities were associated with staying open, suggesting the popularity of
      these attributes. Yelp consumer reviews is a useful research tool to identify
      consumer-determined important sustaining attributes of vape shops and may be used
      to identify aspects of enduring shops that need regulations.

PMID- 29057378
TI  - Systems biology in the central nervous system: a brief perspective on essential
      recent advancements.
AB  - As recent advances in human genetics have begun to more rapidly identify the
      individual genes contributing to risk of psychiatric disease, the spotlight now
      turns to understanding how disruption of these genes alters the brain, and thus
      behavior. Compared to other tissues, cellular complexity in the brain provides
      both a substantial challenge and a significant opportunity for systems biology
      approaches. Current methods are maturing that will allow for finally defining the
      'parts list' for the functioning mouse and human brains, enabling new approaches
      to defining how the system goes awry in disorders of the CNS. However, the
      availability of tissue is certainly a challenge for systems biology of
      neuroscience, compared to systems biology of other tissues, where biopsy is
      feasible. This challenge is particularly notable for disorders caused by
      extremely rare genetic variants. Thus computational and systems biology
      approaches, as well as precise experimental models by way of genome editing, will
      play key roles in defining mechanisms for disorders, and their individual
      symptoms, across varied genetic etiologies. Here, we highlight recent progress in
      neurogenetics, postmortem genomics, cell-type specific profiling, and precision
      modeling toward defining mechanisms in disease.

PMID- 29057380
TI  - Sarcopenia prevalence using simple measurements and population-based cutoff
      values.
AB  - OBJECTIVE: To estimate the prevalence of sarcopenia in Mexican older adults using
      simple measurements and tailored cutoff values for the components of the European
      Working Group on Sarcopenia in Older People algorithm. MATERIAL AND METHODS: This
      study used cross-sectional data from the third wave (2012) of the Mexican Health
      and Aging Study. Gait speed and handgrip strength cutoff values were tailored for
      Mexican older adults. Muscle mass was estimated by a formula, which uses simple
      anthropometry and demographic characteristics. RESULTS: From the total of 1,238
      older adults included in our study, sarcopenia prevalence was 11% (n = 137). When
      categorizing sarcopenia, 39.1% (n = 484) had pre-sarcopenia, 8.3% (n = 103)
      moderate sarcopenia, and 2.75% (n = 34) had severe sarcopenia. CONCLUSIONS:
      Sarcopenia is a common problem in Mexican older adults, and its frequency along
      with its severity increases with age. Tailored cutoff values could help in
      identifying those subjects that could have benefited from intervention.

PMID- 29057381
TI  - Association of Sleep Duration, Symptoms, and Disorders with Mortality in Adults
      with Chronic Kidney Disease.
AB  - INTRODUCTION: In general populations, short and long sleep duration, poor sleep
      quality and sleep disorders have been associated with increased risk of death. We
      evaluated these associations in individuals with chronic kidney disease (CKD).
      METHODS: Prospective cohort study of 1,452 National Health and Nutrition
      Examination Survey (NHANES) 2005-2008 participants with CKD. CKD was defined by
      estimated glomerular filtration rate <60 ml/min/1.73m2 or urine albumin-to
      creatinine ratio >=30 mg/g. Sleep duration, sleep symptoms (difficulty falling
      asleep, difficulty staying asleep, daytime sleepiness and non-restorative sleep),
      and sleep disorders (restless legs syndrome and sleep apnea) were self-reported.
      Vital status was determined using NHANES mortality linkage through December 2011.
      RESULTS: Mean age was 61 years, 58% were women, and 75% non-Hispanic white.
      During 4.4 years of median follow-up, we observed 234 deaths of which 75 were due
      to cardiovascular causes. In multivariable analyses, compared with individuals
      who reported 7-8 hours of sleep, HR (95% CI) for all-cause mortality for sleep
      duration <7 hours and >8 hours were 1.50 (1.08-2.10) and 1.36 (0.89-2.08),
      respectively. The corresponding HR (95%CI) for cardiovascular mortality were 1.56
      (0.72-3.37) and 1.56 (0.66-3.65). Non-restorative sleep and restless legs
      syndrome were associated with increased risk for all-cause mortality (1.63 [1.13
      2.35], and 1.69 [1.04-275], respectively). CONCLUSION: In adults with CKD, short
      sleep duration, nonrestorative sleep and restless legs syndrome are associated
      with increased risk of death. These findings underscore the importance of
      promoting adequate sleep in patients with CKD, and the need for future studies
      evaluating the impact of sleep interventions in this population.

PMID- 29057382
TI  - Ethnic variations in sexual behaviours and sexual health markers: findings from
      the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).
AB  - BACKGROUND: Sexual health entails the absence of disease and the ability to lead
      a pleasurable and safe sex life. In Britain, ethnic inequalities in diagnoses of
      sexually transmitted infections (STI) persist; however, the reasons for these
      inequalities, and ethnic variations in other markers of sexual health, remain
      poorly understood. We investigated ethnic differences in hypothesised explanatory
      factors such as socioeconomic factors, substance use, depression, and sexual
      behaviours, and whether they explained ethnic variations in sexual health markers
      (reported STI diagnoses, attendance at sexual health clinics, use of emergency
      contraception, and sexual function). METHODS: We analysed probability survey data
      from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal
      3; n=15 162, conducted in 2010-12). Reflecting Britain's current ethnic
      composition, we included in our analysis participants who identified in 2011 as
      belonging to one of the following seven largest ethnic groups: white British,
      black Caribbean, black African, Indian, Pakistani, white other, and mixed
      ethnicity. We calculated age-standardised estimates and age-adjusted odds ratios
      for all explanatory factors and sexual health markers for all these ethnic groups
      with white British as the reference category. We used multivariable regression to
      examine the extent to which adjusting for explanatory factors explained ethnic
      variations in sexual health markers. FINDINGS: We included 14 563 (96.0%) of the
      15 162 participants surveyed in Natsal-3. Greater proportions of black Caribbean,
      black African, and Pakistani people lived in deprived areas than those of other
      ethnic groups (36.9-55.3% vs 16.4-29.4%). Recreational drug use was highest among
      white other and mixed ethnicity groups (25.6-27.7% in men and 10.3-12.9% in women
      in the white other and mixed ethnicity groups vs 4.1-15.6% in men and 1.0-11.2%
      in women of other ethnicities). Compared with white British men, the proportions
      of black Caribbean and black African men reporting being sexually competent at
      sexual debut were lower (32.9% for black Caribbean and 21.9% for black African vs
      47.4% for white British) and the number of partners in the past 5 years was
      greater (median 2 [IQR 1-4] for black Caribbean and 2 [1-5] for black African vs
      1 [1-2] for white British), and although black Caribbean and black African men
      reported greater proportions of concurrent partnerships (26.5% for black
      Caribbean and 38.9% for black African vs 14.8% for white British), these
      differences were not significant after adjusting for age. Compared with white
      British women, the proportions of black African and mixed ethnicity women
      reporting being sexually competent were lower (18.0% for black African and 35.3%
      for mixed ethnicity vs 47.9% for white British), and mixed ethnicity women
      reported larger numbers of partners in the past 5 years (median 1 [IQR 1-4] vs 1
      [1-2]) and greater concurrency (14.3% vs 8.0%). Reporting STI diagnoses was
      higher in black Caribbean men (8.7%) and mixed ethnicity women (6.7%) than white
      British participants (3.6% in men and 3.2% in women). Use of emergency
      contraception was most commonly reported among black Caribbean women (30.7%). Low
      sexual function was most common among women of white other ethnicity (30.1%).
      Adjustment for explanatory factors only partly explained inequalities among some
      ethnic groups relative to white British ethnicity but did not eliminate ethnic
      differences in these markers. INTERPRETATION: Ethnic inequalities in sexual
      health markers exist, and they were not fully explained by differences in their
      broader determinants. Holistic interventions addressing modifiable risk factors
      and targeting ethnic groups at risk of poor sexual health are needed. FUNDING:
      Medical Research Council, the Wellcome Trust, the Economic and Social Research
      Council, UK Department of Health, and The National Institute for Health Research.

PMID- 29057383
TI  - Regulation of Keap1-Nrf2 signaling: The role of epigenetics.
AB  - Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related
      factor 2 (NFE2L2/Nrf2) signaling pathway is a pivotal player in the antioxidant
      response to oxidative and electrophilic stress and can play a role in many human
      diseases. Activation or inhibition of Nrf2 has been an approach to treating many
      diseases such as cancer and regulation of this pathway has been thoroughly
      studied. Recently, epigenetics has emerged as another layer for regulating Keap1
      Nrf2. Epigenetics modification is defined as heritable changes to gene expression
      without changing DNA sequence and various modifications have been found to be
      involved in regulating Keap1-Nrf2. Therefore, targeting these epigenetic changes
      on Keap1-Nrf2 provides a potential pathway for modulating Keap1-Nrf2 to treat
      disease. In this review, several important and recent findings on epigenetic
      regulation and perspectives on Keap1-Nrf2 are discussed and shared.

PMID- 29057384
TI  - Concise Review: Current and Emerging Biomarkers of Nephrotoxicity.
AB  - The kidney is a primary organ for filtration of the blood and elimination of
      drugs and xenobiotics. These active reabsorptive and secretory processes can
      result in acute kidney injury as a result of these concentrative properties.
      Classic measures of acute kidney injury are hampered by their ability to
      accurately assess function before irreversible damage has occurred. This review
      will discuss efforts to refine the clinical utility of standard biomarkers as
      well as the development of novel biomarkers of nephrotoxicity.

PMID- 29057385
TI  - A Network Neuroscience of Neurofeedback for Clinical Translation.
AB  - In the emerging field of network neuroscience, the brain is represented as a
      network of discrete yet functionally and structurally interconnected areas.
      Mathematical and computational tools to characterize the organization of this
      network can provide insights into the principles guiding brain structure and
      function, and can pinpoint differences between healthy individuals and
      individuals suffering from psychiatric disease or neurological disorders. The
      field is now faced with the question of how to devise clinical interventions that
      target these network alterations. Potential solutions to this question include
      the combination of emerging theories of network control with cutting-edge
      interventions such as neurofeedback. Each of these techniques may now be mature
      enough to combine to obtain a theoretically-motivated framework informing viable
      neuropsychiatric therapies.

PMID- 29057386
TI  - Sensitivity and Specificity of OCT Angiography to Detect Choroidal
      Neovascularization.
AB  - PURPOSE: To determine the sensitivity and specificity of optical coherence
      tomography angiography (OCTA) in the detection of choroidal neovascularization
      (CNV) in age-related macular degeneration (AMD). DESIGN: Prospective case series.
      SUBJECTS: Prospective series of seventy-two eyes were studied, which included
      eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal
      controls. METHODS: All eyes underwent OCTA with a spectral domain (SD) OCT
      (Optovue, Inc.). The 3D angiogram was segmented into separate en face views
      including the inner retinal angiogram, outer retinal angiogram, and
      choriocapillaris angiogram. Detection of abnormal flow in the outer retina served
      as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face
      OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence
      of CNV. MAIN OUTCOME MEASURE: The sensitivity and specificity of CNV detection
      compared to the gold standard of fluorescein angiography (FA) and OCT was
      determined for structural SD-OCT alone, en face OCTA alone, and with en face OCTA
      combined with cross-sectional OCTA. RESULTS: Of 32 eyes with CNV, both graders
      identified 26 true positives with en face OCTA alone, resulting in a sensitivity
      of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage (SRH) and
      sensitivity improved to 94% for both graders if eyes with SRH were excluded. The
      addition of cross-sectional OCTA along with en face OCTA improved the sensitivity
      to 100% for both graders. Structural OCT alone also had a sensitivity of 100%.
      The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader
      B. The specificity of structural OCT alone was 97.5% for grader A and 85% for
      grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of
      97.5% for grader A and 100% for grader B. CONCLUSIONS: Sensitivity and
      specificity for CNV detection with en face OCTA combined with cross-sectional
      OCTA approaches that of the gold standard of FA with OCT, and it is better than
      en face OCTA alone. Structural OCT alone has excellent sensitivity for CNV
      detection. False positives from structural OCT can be mitigated with the addition
      of flow information with OCTA.

PMID- 29057387
TI  - Toward solving the etiological mystery of primary biliary cholangitis.
AB  - Primary biliary cholangitis (PBC) is considered a model autoimmune disease due to
      its signature AMA autoantibody, female predominance and relatively specific
      portal infiltration and cholestasis. The identification and cloning of the major
      mitochondrial autoantigens, recognized by AMA, have served as an immunologic
      platform to identify the earliest events involved in loss of tolerance. Despite
      the relative high concordance rate in identical twins, genome wide association
      studies have not proven clinically useful and have led to suggestions of
      epigenetic events. To understand the natural history and etiology of PBC, several
      murine models have been developed including spontaneous models, models induced by
      chemical xenobiotic immunization and by "designer" mice with altered interferon
      metabolism. Herein, we describe five such models including 1) NOD.c3c4 mice, 2)
      dominant negative form of transforming growth factor (TGF)-beta receptor type II
      (dnTGFbetaRII) mice, 3) interleukin (IL)-2Ralpha-/- mice 4) ARE Del-/-mice and 5)
      2-octynoic acid conjugated bovine serum albumin (2OA-BSA) immunized mice.
      Individually there is no perfect murine model but collectively the models point
      to loss of tolerance to PDC-D2, the major mitochondrial autoantigen, as the
      earliest event that occurs before clinical disease is manifest. Although there is
      no direct association of AMA titer and PBC disease progression it is noteworthy
      that the triad of PBC monocytes, biliary apotopes and AMA leads to an intense
      proinflammatory cytokine burst. Further the recurrence of PBC after liver
      transplantation indicates that, due to MHC restriction, disease activity must
      include not only adaptive immunity but also innate immune mechanisms. We
      postulate that successful treatment of PBC may require a personalized approach
      with therapies designed for different stages of disease.

PMID- 29057388
TI  - Overlapping Risky Decision-Making and Olfactory Processing Ability in HIV
      Infected Individuals.
AB  - OBJECTIVE: Given neuroimaging evidences of overlap in the circuitries for
      decision-making and olfactory processing, we examined the hypothesis that
      impairment in psychophysical tasks of olfaction would independently predict poor
      performances on Iowa Gambling Task (IGT), a laboratory task that closely mimics
      real-life decision-making, in a US cohort of HIV-infected (HIV+) individuals.
      METHOD: IGT and psychophysical tasks of olfaction were administered to a
      Washington DC-based cohort of largely African American HIV+ subjects (N=100), and
      to a small number of demographically-matched non-HIV healthy controls (N=43) from
      a different study. Constructs of olfactory ability and decision-making were
      examined through confirmatory factor analysis (CFA). Structural equation models
      (SEMs) were used to evaluate the validity of the path relationship between these
      two constructs. RESULT: The 100 HIV+ participants (56% female; 96% African
      Americans; median age = 48 years) had median CD4 count of 576 cells/MUl and
      median HIV RNA viral load <48 copies per milliliter. Majority of HIV+
      participants performed randomly throughout the course of IGT tasks, and failed to
      demonstrate a learning curve. Confirmatory factor analysis provided support for a
      unidimensional factor underlying poor performances on IGT. Nomological validity
      for correlations between olfactory ability and IGT performance was confirmed
      through SEM. Finally, factor scores of olfactory ability and IGT performance
      strongly predicted 6 months history of drug use, while olfaction additionally
      predicted hallucinogen use. CONCLUSION: This study suggests that combination of
      simple, office-based tasks of olfaction and decision-making may identify those
      HIV+ individuals who are more prone to risky decision-making. This finding may
      have significant clinical, public health value if joint impairments in olfaction
      and IGT task correlates with more decreased activity in brain regions relevant to
      decision-making.

PMID- 29057390
TI  - Meaningfully Engaging Patients in ACO Decision Making.

PMID- 29057391
TI  - Agent specific effects of anticoagulant induced alopecia.
AB  - Alopecia has been observed with many anticoagulants although the mechanism is
      unclear. A 20 year old female with recurrent DVTs developed alopecia with
      multiple anticoagulants, including heparin derivatives and the new oral
      anticoagulants. This resolved with discontinuation of the agents. The patient was
      ultimately able to be anticoagulated with fondaparinux long term without any
      alopecia. This case addresses the key clinical question of management and
      recognition of anticoagulant induced alopecia. This side effect can result from
      almost any of the available agents and is quickly reversible, underlining the
      importance of tailoring treatment to the individual and their experiences.

PMID- 29057392
TI  - Drought and the risk of hospital admissions and mortality in older adults in
      western USA from 2000 to 2013: a retrospective study.
AB  - BACKGROUND: Occurrence, severity and geographic extent of droughts are
      anticipated to increase under climate change, but the health consequences of
      drought conditions are unknown. We estimate risks of cardiovascular and
      respiratory-related hospitalization and mortality associated with drought
      conditions for the western U.S. elderly population. METHODS: For counties in the
      western U.S. (N=618) and for the period 2000 to 2013, we use data from the U.S.
      Drought Monitor to identify: 1) full drought periods; 2) non-drought periods; and
      3) worsening drought periods stratified by low- and high-severity. We use
      Medicare claims to calculate daily rates of cardiovascular admissions,
      respiratory admissions, and deaths among adults 65 years or older. Using a two
      stage hierarchical model, we estimated the percentage change in health risks when
      comparing drought to non-drought period days controlling for daily weather and
      seasonal trends. FINDINGS: On average there were 2.1 million days and 0.6 million
      days classified as non-drought periods and drought periods, respectively.
      Compared to non-drought periods, respiratory admissions significantly decreased
      by -1.99% (95% posterior interval (PI): -3.56, -0.38) during the full drought
      period, but not during worsening drought conditions. Mortality risk significantly
      increased by 1.55% (95% PI: 0.17, 2.95) during the high-severity worsening
      drought period, but not the full drought period. Cardiovascular admissions did
      not differ significantly during either drought or worsening drought periods. In
      counties where drought occurred less frequently, we found risks for
      cardiovascular disease and mortality to increase during worsening drought
      conditions. INTERPRETATIONS: Drought conditions increased risk of mortality
      during high-severity worsening drought, but decreased the risk of respiratory
      admissions during full drought periods among older adults. Counties that
      experience fewer drought events show larger risk for mortality and cardiovascular
      disease. This research describes an understudied environmental association with
      global health significance.

PMID- 29057393
TI  - Motion Estimation with Finite-Element Biomechanical Models and Tracking
      Constraints from Tagged MRI.
AB  - Noninvasive measurements of tissue deformation provide bio-mechanical insights of
      an organ, which can be used as clinical functional biomarkers or experimental
      data for validating computational simulations. However, acquisition of 3D
      displacement information is susceptible to experimental inconsistency and limited
      scan time. In this research, we describe the process of tracking tagged magnetic
      resonance imaging (MRI) as enforcing harmonic phase conservation in finite
      element (FE) models. This concept is demonstrated as a tool for motion estimation
      in a brain motion phantom, the heart, and the tongue. Our results demonstrate
      that the new methodology offers robustness to edge and large-displacement
      artifacts, and that it can be seamlessly coupled with numerical simulations for
      estimating fiber stretch in residually stressed tissue, or for inverse
      identification of muscle activation.

PMID- 29057395
TI  - Parallelizing Affinity Propagation Using Graphics Processing Units for Spatial
      Cluster Analysis over Big Geospatial Data.
AB  - Introduced in 2007, affinity propagation (AP) is a relatively new machine
      learning algorithm for unsupervised classification that has seldom been applied
      in geospatial applications. One bottleneck is that AP could hardly handle large
      data, and a serial computer program would take a long time to complete an AP
      calculation. New multicore and manycore computer architectures, combined with
      application accelerators, show promise for achieving scalable geocomputation by
      exploiting task and data levels of parallelism. This chapter introduces our
      recent progress in parallelizing the AP algorithm on a graphics processing unit
      (GPU) for spatial cluster analysis, the potential of the proposed solution to
      process big geospatial data, and its broader impact for the GIScience community.

PMID- 29057394
TI  - Critical Analysis of White House Anti-Drug Plan.

PMID- 29057396
TI  - Effects of Actigraphically Acquired Sleep Quality onDriving Outcomes in
      Obstructive Sleep Apnea Patientsand Control drivers: A Naturalistic Study.
AB  - We examined the effects of sleep quality on next day driving outcomes in a 3.5
      month naturalistic driving study of 67 OSA and 47 matched control drivers. Sleep
      quality measures included total sleep time and sleep fragmentation from
      actigraphy. The driving outcomes included average speed, lateral control,
      longitudinal control, distraction, attention to driving- and non-driving related
      tasks. Sleep quality affected next day's driving performance differently for OSA
      and control drivers. Better sleep quality was associated with better lateral and
      longitudinal control during highway driving for control drivers. The reverse was
      true for OSA drivers. Similar effects were also seen in terms of distractions and
      attention to the driving task. These effects suggest improved sleep leads to
      greater risky driving and 'activation' among OSA drivers. Collectively, the
      findings suggest investment in long-term monitoring of sleep quality in
      commercial vehicle drivers both with and without sleep disorders may help manage
      safety risks.

PMID- 29057397
TI  - Privacy and Technology: Folk Definitions and Perspectives.
AB  - In this paper we present preliminary results from a study of individual
      differences in privacy beliefs, as well as relate folk definitions of privacy to
      extant privacy theory. Focus groups were conducted with young adults aged 18-28
      and older adults aged 65-75. Participants first shared their individual
      definitions of privacy, followed by a discussion of privacy in six scenarios
      chosen to represent a range of potentially invasive situations. Taken together,
      Westin's and Altman's theories of privacy accounted for both younger and older
      adults' ideas about privacy, however, neither theory successfully accounted for
      findings across all age and gender groups. Whereas males tended to think of
      privacy in terms of personal needs and convenience, females focused more on
      privacy in terms of others, respecting privacy rights, and safety. Older adults
      tended to be more concerned about privacy of space rather than information
      privacy. Initial results reinforce the notion that targeting HCI design to the
      user population, even with respect to privacy, is critically important.

PMID- 29057399
TI  - Molecular rigidity and enthalpy-entropy compensation in DNA melting.
AB  - Enthalpy-entropy compensation (EEC) is observed in diverse molecular binding
      processes of importance to living systems and manufacturing applications, but
      this widely occurring phenomenon is not sufficiently understood from a molecular
      physics standpoint. To gain insight into this fundamental problem, we focus on
      the melting of double-stranded DNA (dsDNA) since measurements exhibiting EEC are
      extensive for nucleic acid complexes and existing coarse-grained models of DNA
      allow us to explore the influence of changes in molecular parameters on the
      energetic parameters by using molecular dynamics simulations. Previous
      experimental and computational studies have indicated a correlation between EEC
      and changes in molecular rigidity in certain binding-unbinding processes, and,
      correspondingly, we estimate measures of DNA molecular rigidity under a wide
      range of conditions, along with resultant changes in the enthalpy and entropy of
      binding. In particular, we consider variations in dsDNA rigidity that arise from
      changes of intrinsic molecular rigidity such as varying the associative
      interaction strength between the DNA bases, the length of the DNA chains, and the
      bending stiffness of the individual DNA chains. We also consider extrinsic
      changes of molecular rigidity arising from the addition of polymer additives and
      geometrical confinement of DNA between parallel plates. All our computations
      confirm EEC and indicate that this phenomenon is indeed highly correlated with
      changes in molecular rigidity. However, two distinct patterns relating to how DNA
      rigidity influences the entropy of association emerge from our analysis.
      Increasing the intrinsic DNA rigidity increases the entropy of binding, but
      increases in molecular rigidity from external constraints decreases the entropy
      of binding. EEC arises in numerous synthetic and biological binding processes and
      we suggest that changes in molecular rigidity might provide a common origin of
      this ubiquitous phenomenon in the mutual binding and unbinding of complex
      molecules.

PMID- 29057398
TI  - COMPUTATIONAL ANALYSIS OF TRAJECTORIES OF LINGUISTIC DEVELOPMENT IN AUTISM.
AB  - Deficits in semantic and pragmatic expression are among the hallmark linguistic
      features of autism. Recent work in deriving computational correlates of clinical
      spoken language measures has demonstrated the utility of automated linguistic
      analysis for characterizing the language of children with autism. Most of this
      research, however, has focused either on young children still acquiring language
      or on small populations covering a wide age range. In this paper, we extract
      numerous linguistic features from narratives produced by two groups of children
      with and without autism from two narrow age ranges. We find that although many
      differences between diagnostic groups remain constant with age, certain pragmatic
      measures, particularly the ability to remain on topic and avoid digressions, seem
      to improve. These results confirm findings reported in the psychology literature
      while underscoring the need for careful consideration of the age range of the
      population under investigation when performing clinically oriented computational
      analysis of spoken language.

PMID- 29057400
TI  - A Cu3P-CoP hybrid nanowire array: a superior electrocatalyst for acidic hydrogen
      evolution reactions.
AB  - It is highly attractive to construct cost-effective hybrid electrocatalysts with
      superior activity for the hydrogen evolution reaction (HER) in acids. In this
      communication, we report a novel structure consisting of a Cu3P-CoP hybrid
      nanowire array supported on carbon cloth (Cu3P-CoP/CC) as a superior HER
      electrocatalyst in acidic media. Owing to the synergistic effect between Cu3P and
      CoP, this Cu3P-CoP/CC catalyst exhibits superior catalytic HER performance,
      needing an overpotential of 59 mV to drive a current density of 10 mA cm-2 in 0.5
      M H2SO4, 24 and 130 mV less than that for CoP/CC and Cu3P/CC, respectively.
      Moreover, this catalyst also shows high long-term electrochemical durability.

PMID- 29057401
TI  - A model of cell-wall dynamics during sporulation in Bacillus subtilis.
AB  - To survive starvation, Bacillus subtilis forms durable spores. After asymmetric
      cell division, the septum grows around the forespore in a process called
      engulfment, but the mechanism of force generation is unknown. Here, we derived a
      novel biophysical model for the dynamics of cell-wall remodeling during
      engulfment based on a balancing of dissipative, active, and mechanical forces. By
      plotting phase diagrams, we predict that sporulation is promoted by a line
      tension from the attachment of the septum to the outer cell wall, as well as by
      an imbalance in turgor pressures in the mother-cell and forespore compartments.
      We also predict that significant mother-cell growth hinders engulfment. Hence,
      relatively simple physical principles may guide this complex biological process.

PMID- 29057402
TI  - Programming the mechanics of cohesive fiber networks by compression.
AB  - Fibrous networks are ideal functional materials since they provide mechanical
      rigidity at low weight. Here, we demonstrate that fibrous networks of the blood
      clotting protein fibrin undergo a strong and irreversible increase in their
      mechanical rigidity in response to uniaxial compression. This rigidification can
      be precisely controlled by the level of applied compressive strain, providing a
      means to program the network rigidity without having to change its composition.
      To identify the underlying mechanism we measure single fiber-fiber interactions
      using optical tweezers. We further develop a minimal computational model of
      cohesive fiber networks that shows that stiffening arises due to the formation of
      new bonds in the compressed state, which develop tensile stress when the network
      is re-expanded. The model predicts that the network stiffness after a compression
      cycle obeys a power-law dependence on tensile stress, which we confirm
      experimentally. This finding provides new insights into how biological tissues
      can adapt themselves independently of any cellular processes, offering new
      perspectives to inspire the design of reprogrammable materials.

PMID- 29057404
TI  - Improving Na-O2 batteries with redox mediators.
AB  - A new route to enhance the performance of Na-O2 cells is demonstrated. Redox
      mediators (such as ethyl viologen) are shown to facilitate the discharge
      reaction, producing an increased capacity (due to suppressed electrode
      passivation), higher discharge potential (due to faster kinetics) and stable
      cycling.

PMID- 29057403
TI  - Fluorogenic reaction-based prodrug conjugates as targeted cancer theranostics.
AB  - Theranostic systems are receiving ever-increasing attention due to their
      potential therapeutic utility, imaging enhancement capability, and promise for
      advancing the field of personalized medicine, particularly as it relates to the
      diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide
      an introduction to the concepts of theranostic drug delivery effected via use of
      conjugates that are able to target cancer cells selectively, provide cytotoxic
      chemotherapeutics, and produce readily monitored imaging signals in vitro and in
      vivo. The underlying design concepts, requiring the synthesis of conjugates
      composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers,
      and cancer targeting ligands, are discussed. Particular emphasis is placed on
      highlighting the potential benefits of fluorogenic reaction-based targeted
      systems that are activated for both imaging and therapy by cellular entities,
      e.g., thiols, reactive oxygen species and enzymes, which are present at
      relatively elevated levels in tumour environments, physiological characteristics
      of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by
      an external stimulus, such as light. The work summarized in this Tutorial Review
      will help define the role fluorogenic reaction-based, cancer-targeting
      theranostics may have in advancing drug discovery efforts, as well as improving
      our understanding of cellular uptake and drug release mechanisms.

PMID- 29057406
TI  - A direct access to heterobimetallic complexes by roll-over cyclometallation.
AB  - Complexes of the type [Cp*Ir(N,N')Cl]+ (N,N' = 2-(2-dialkylaminopyrimidin-4
      yl)pyrimidine) can undergo roll-over cyclometallation leading to a novel N,N'
      donor site. Following this strategy heterobimetallic complexes including
      iridium(iii) and a Group X metal centre in the oxidation state +II were achieved.

PMID- 29057405
TI  - Switching enzyme specificity from phosphate to resveratrol glucosylation.
AB  - Here we present a point mutation-triggered domain shift which switches the
      acceptor preference of a sucrose phosphorylase from phosphate to a variety of
      large polyphenolic compounds including resveratrol and quercetin, enabling their
      efficient glucosylation. The variant possesses a high affinity for aromatic
      substrates due to newly introduced pi-pi- and hydrophobic interactions in the
      altered active site. The domain shift brings about a substantially enlarged and
      multifunctional active site for polyphenol glucosylation and rare disaccharide
      production. The crystal structure of the variant with its product resveratrol-3
      alpha-d-glucoside allows the prediction of the substrate scope and
      regioselectivity of the aromatic compounds' glucosylation sites.

PMID- 29057407
TI  - Polymer-mediated metallophilic interactions for gram-scale production, high-yield
      (~90%) synthesis of ultrathin bismuth nanowires.
AB  - High-yields (~90%) of ultrathin (<4 nm) bismuth nanowires (Bi UNWs) were obtained
      by reducing the polymeric strands of oleylamine-bismuth 2-ethylhexanoate
      complexes formed via metallophilic interactions with the mediation of a copolymer
      (PVP-HDE).

PMID- 29057408
TI  - Co-encapsulation of CdSe/ZnS and CeO2 nanoparticles in waterborne polymer
      dispersions: enhancement of fluorescence emission under sunlight.
AB  - Hybrid core/shell polymer particles with co-encapsulated quantum dots (QDs)
      (CdSe/ZnS) and CeO2 nanoparticles have been synthesized in a two stage semi-batch
      emulsion polymerization process. In the first stage, both inorganic nanoparticles
      are incorporated into cross-linked polystyrene (PS) particles by miniemulsion
      polymerization. This hybrid dispersion is then used as the seed to produce the
      core/shell particles by starved feeding of methyl methacrylate and divinylbenzene
      (MMA/DVB) monomers. The core/shell hybrid dispersions maintained in the dark
      exhibit stable fluorescence emission over time, and notably their fluorescence
      intensity increases under sunlight, likely due to the effect of the co
      encapsulated CeO2 nanoparticles that change the optical properties of the
      environment of the quantum dot particles. The fluorescence increase depends on
      the QD : CeO2 ratio, with the 1 : 2 ratio resulting in the highest increase
      (280%). Furthermore, a film forming hybrid latex has been synthesized using the
      former core/shell PS/QD/CeO2/PMMA particles as seeds and feeding under semi-batch
      conditions methyl methacrylate, butyl acrylate and acrylic acid. Films cast from
      this core/shell/shell hybrid dispersion also exhibit fluorescence, and as for the
      core/shell latex the fluorescence increases under sunlight exposure.
      Interestingly, the increase in the film is at least two times higher than that in
      the latex, which is attributed to the additional effect of the neighboring
      coalesced particles containing CeO2 affecting the environment of the QDs.

PMID- 29057409
TI  - Controlled fabrication of osmium nanocrystals by electron, laser and microwave
      irradiation and characterisation by microfocus X-ray absorption spectroscopy.
AB  - Osmium nanocrystals can be fabricated by electron (3-50 nm, formed by atom
      migration), 785-815 nm laser (20-50 nm, in micelle islands), and microwave (ca. 1
      nm in arrays, >100 mg scale) irradiation of a polymer-encapsulated OsII
      carborane; microfocus X-ray absorption studies at the Os LIII-edge show
      differences between the three preparation methods, suggesting that the electron
      beam irradiated materials have a significant support interaction and/or surface
      oxidation, while the laser and microwave samples are more like metallic osmium.

PMID- 29057410
TI  - A detailed experimental and theoretical investigation of the role of cyano groups
      in the pi-bridged acceptor of sensitizers for use in dye-sensitized solar cells
      (DSCs).
AB  - Three donor-pi conjugated unit-acceptor (D-pi-A) type zinc porphyrin sensitizers
      LX1, LX2 and LX3 bearing meso acrylic acid, alpha-cyanoacrylic acid, and alpha
      cyanopentadienoic acid, respectively, as the pi-bridged acceptors were designed
      and synthesized for use in dye-sensitized solar cells (DSCs). The interesting
      role of the cyano group attached to the alpha position of the acrylic and
      pentadienoic acid acceptor was investigated. It was shown that even though the
      introduction of the cyano group and the elongation of the pi-bridge can both
      increase the light-harvesting as indicated by the UV-vis absorption spectra, the
      relevant cell performance dropped significantly. The photo to power conversion
      efficiencies (PCEs) of the devices increase in the order of LX1 > LX2 > LX3, with
      the highest PCE of 6.04% achieved for the LX1-based cell, which bears acrylic
      acid as the pi-bridged acceptor. To further explore the effect of -CN and 
      CH[double bond, length as m-dash]CH- on the interaction between the absorbed dye
      and TiO2 substrates, their density of states (DOS) and partial density of states
      (PDOS), as well as electronic properties were investigated in detail using
      theoretical calculations. The results suggest that introducing the -CN group into
      the acceptor and extending the conjugation of the pi-bridge have decreased the
      LUMO levels of the dyes, leading to weak interfacial coupling, low electron
      injection driving force, low Jsc, and thus poor cell performance.

PMID- 29057411
TI  - Exploring the effect of fluorinated anions on the CO2/N2 separation of supported
      ionic liquid membranes.
AB  - The CO2 and N2 permeation properties of ionic liquids (ILs) based on the 1-ethyl
      3-methylimidazolium cation ([C2mim]+) and different fluorinated anions, namely
      2,2,2-trifluoromethylsulfonyl-N-cyanoamide ([TFSAM]-), bis(fluorosulfonyl) imide
      ([FSI]-), nonafluorobutanesulfonate ([C4F9SO3]-),
      tris(pentafluoroethyl)trifluorophosphate ([FAP]-), and
      bis(pentafluoroethylsulfonyl)imide ([BETI]-) anions, were measured using
      supported ionic liquid membranes (SILMs). The results show that pure ILs
      containing [TFSAM]- and [FSI]- anions present the highest CO2 permeabilities, 753
      and 843 Barrer, as well as the greatest CO2/N2 permselectivities of 43.9 and
      46.1, respectively, with CO2/N2 separation performances on top of or above the
      Robeson 2008 upper bound. The re-design of the [TFSAM]- anion by structural
      unfolding was investigated through the use of IL mixtures. The gas transport and
      CO2/N2 separation properties through a pure [C2mim][TFSAM] SILM are compared to
      those of two different binary IL mixtures containing fluorinated and cyano
      functionalized groups in the anions. Although the use of IL mixtures is a
      promising strategy to tailor gas permeation through SILMs, the pure
      [C2mim][TFSAM] SILM displays higher CO2 permeability, diffusivity and solubility
      than the selected IL mixtures. Nevertheless, both the prepared mixtures present
      CO2 separation performances that are on top of or above the Robeson plot.

PMID- 29057412
TI  - Correction: Core-excited and shape resonances of uracil.
AB  - Correction for 'Core-excited and shape resonances of uracil' by Mark A. Fennimore
      et al., Phys. Chem. Chem. Phys., 2016, 18, 30536-30545.

PMID- 29057413
TI  - Revealing vilazodone's binding mechanism underlying its partial agonism to the 5
      HT1A receptor in the treatment of major depressive disorder.
AB  - It has been estimated that major depressive disorder (MDD) will become the second
      largest global burden among all diseases by 2030. Various types of drugs,
      including selective serotonin reuptake inhibitors (SSRIs), serotonin
      norepinephrine reuptake inhibitors (SNRIs), and serotonin receptor partial
      agonist/reuptake inhibitors (SPARIs), have been approved and become the primary
      or first-line medications prescribed for MDD. SPARI was expected to demonstrate
      more enhanced drug efficacy and a rapid onset of action as compared to SSRI and
      SNRI. As one of the most famous SPARIs, vilazodone was approved by the FDA for
      the treatment of MDD. Because of the great clinical importance of vilazodone, its
      binding mechanism underlying its partial agonism to the 5-HT1A receptor (5-HT1AR)
      could provide valuable information to SPARIs' drug-like properties. However, this
      mechanism has not been reported to date; consequently, the rational design of new
      efficacious SPARI-based MDD drugs is severely hampered. To explore the molecular
      mechanism of vilazodone, an integrated computational strategy was adopted in this
      study to reveal its binding mechanism and prospective structural feature at the
      agonist binding site of 5-HT1AR. As a result, 22 residues of this receptor were
      identified as hotspots, consistently favoring the binding of vilazodone and its
      analogues, and a common binding mechanism underlying their partial agonism to 5
      HT1AR was, therefore, discovered. Moreover, three main interaction features
      between vilazodone and 5-HT1AR have been revealed and schematically summarized.
      In summary, this newly identified binding mechanism will provide valuable
      information for medicinal chemists working in the field of rational design of
      novel SPARIs for MDD treatment.

PMID- 29057414
TI  - Salt-induced thermochromism of a conjugated polyelectrolyte.
AB  - We report here the photophysical properties of a water-soluble conjugated
      polythiophene with cationic side-chains. When dissolved in aqueous buffer
      solution (PBS, phosphate buffered saline), there is ordering of the polymer
      chains due to the presence of the salts, in contrast to pure water, where a
      random-coil conformation is adopted at room temperature. The ordering leads to a
      pronounced colour change of the solution (the absorption maximum shifts from 400
      nm to 525 nm). Combining resonance Raman spectroscopy with density functional
      theory computations, we show a significant backbone planarization in the ordered
      phase. Moreover, the ratio of ordered phase to random-coil phase in PBS solution,
      as well as the extent of intermolecular interactions in the ordered phase, can be
      tuned by varying the temperature. Femtosecond transient absorption spectroscopy
      reveals that the excited-state behaviour of the polyelectrolyte is strongly
      affected by the degree of ordering. While triplet state formation is favoured in
      the random-coil chains, the ordered chains show a weak yield of polarons, related
      to interchain interactions. The investigated polyelectrolyte has been previously
      used as a biological DNA sensor, based on optical transduction when the
      conformation of the polyelectrolyte changes during assembly with the biomolecule.
      Therefore, our results, by correlating the photophysical properties of the
      polyelectrolyte to backbone and intermolecular conformation in a biologically
      relevant buffer, provide a significant step forward in understanding the
      mechanism of the biological sensing.

PMID- 29057415
TI  - Molecular details of the unique mechanism of chloride transport by a
      cyanobacterial rhodopsin.
AB  - Microbial rhodopsins are well known as versatile and ubiquitous light-driven ion
      transporters and photosensors. While the proton transport mechanism has been
      studied in great detail, much less is known about various modes of anion
      transport. Until recently, only two main groups of light-driven anion pumps were
      known, archaeal halorhodopsins (HRs) and bacterial chloride pumps (known as ClRs
      or NTQs). Last year, another group of cyanobacterial anion pumps with a very
      distinct primary structure was reported. Here, we studied the chloride
      transporting photocycle of a representative of this new group, Mastigocladopsis
      repens rhodopsin (MastR), using time-resolved spectroscopy in the infrared and
      visible ranges and site-directed mutagenesis. We found that, in accordance with
      its unique amino acid sequence containing many polar residues in the
      transmembrane region of the protein, its photocycle features a number of unusual
      molecular events not known for other anion-pumping rhodopsins. It appears that
      light-driven chloride ion transfers by MastR are coupled with translocation of
      protons and water molecules as well as perturbation of several polar sidechains.
      Of particular interest is transient deprotonation of Asp-85, homologous to the
      cytoplasmic proton donor of light-driven proton pumps (such as Asp-96 of
      bacteriorhodopsin), which may serve as a regulatory mechanism.

PMID- 29057416
TI  - Formation of pyrimidine-pyrimidine type DNA intrastrand cross-links: a
      theoretical verification.
AB  - Pyrimidine-type radicals have been demonstrated to be able to attack their 3' or
      5' neighboring purine nucleotides forming diverse DNA intrastrand cross-links,
      but whether or not these radicals can attack their surrounding pyrimidine
      nucleotides forming pyrimidine-pyrimidine type DNA intrastrand cross-links
      remains unclear. To resolve this question, probable additions of the uracil-5
      methyl (UCH2) radical to the C5[double bond, length as m-dash]C6 double bond of
      its 3'/5' neighboring pyrimidine nucleotides in the four models, 5'-T(UCH2)-3',
      5'-C(UCH2)-3', 5'-(UCH2)T-3', and 5'-(UCH2)C-3', are explored in the present work
      employing density functional theory (DFT) methods. The C6 site of its 5'
      neighboring thymidine is the preferred target for UCH2 radical addition, while
      additions of the UCH2 radical to the C6 and C5 sites of its 5' neighboring
      deoxycytidine are found to be competitive reactions. The UCH2 radical can react
      with both the C6 and C5 sites of its 3' neighboring pyrimidine nucleotides, but
      the efficiencies of these reactions are predicted to be much lower than those of
      the corresponding addition reactions to its 5' neighboring pyrimidine
      nucleotides, indicating the existence of an obvious sequence effect. All the
      addition products could be finally transformed into closed-shell intrastrand
      cross-links, the molecular masses of which are found to be exactly the same as
      certain MS values determined in a recent study of an X-irradiated deoxygenated
      aqueous solution of calf thymus DNA. The present study thus not only definitely
      corroborates the fact that the reactive UCH2 radical can attack its 3'/5'
      neighboring pyrimidine nucleotides forming several pyrimidine-pyrimidine type DNA
      intrastrand cross-links, but also provides a plausible explanation for the
      identities of these structurally unknown intrastrand cross-links.

PMID- 29057417
TI  - Long-range magnetic order in the porous metal-organic framework
      Ni(pyrazine)[Pt(CN)4].
AB  - A combined study involving DFT calculations, neutron scattering, heat capacity
      and magnetic measurements at very low temperatures demonstrates the long-range
      magnetic ordering of Ni(pyrazine)[Pt(CN)4] below 1.9 K, describing its
      antiferromagnetic spin arrangement. This compound belongs to the family of porous
      coordination polymers M(pyrazine)[Pt(CN)4] (M = divalent metal), renowned for
      showing interesting combinations of porosity and magnetic properties. The
      possibility of including long-range magnetic ordering, one of the most pursued
      functional properties, opens new perspectives for the multifunctionality of this
      class of compounds.

PMID- 29057418
TI  - The reaction of Criegee intermediates with acids and enols.
AB  - The reaction of CH2OO, the smallest carbonyl oxide (Criegee intermediate, CI),
      with several acids was investigated using the CCSD(T)/aug-cc-pVTZ//M06-2X/aug-cc
      pVTZ quantum chemical method, as well as microvariational transition state theory
      and RRKM master equation theoretical kinetic methodologies. For oxoacids HNO3 and
      HCOOH, a 1,4-insertion mechanism allows for barrierless reactions with high rate
      coefficients, in agreement with literature experimental data. This mechanism
      relies on the presence of a double bond in the alpha-position to the acidic OH
      group. We predict that reactions of CI with enols will likewise have high rate
      coefficients, proceeding through a similar mechanism. The hydracid HCl was found
      to react through a less favorable 1,2-insertion reaction, leading to lower rate
      coefficients, again in good agreement with the literature. We conclude that the
      reaction mechanism is the main indicator for the reaction rate for CH2OO + acid
      reactions, with acidity only of secondary influence. At room temperature and 1
      atm the main product for all reactions was found to be the thermalized
      hydroperoxide initial adduct, with minor yields of fragmentation products. One of
      the product channels characterized is a novel reaction path involving
      intramolecular H-abstraction after a roaming reaction in the OH + product radical
      complex formed by the dissociation of the hydroperoxide adduct; this channel is
      the lowest fragmentation route for some of the reactions studied.

PMID- 29057419
TI  - Density functional theory modeling of C-Au chemical bond formation in gold
      implanted polyethylene.
AB  - We have studied processes of gold ion implantation in polyethylene (PE) by
      theoretical chemistry methods. Car-Parrinello molecular dynamics (CPMD)
      simulations of collisions and following chemical kinetics considerations lead to
      the conclusion that chemical bonds between gold atoms and PE chains are formed.
      We have identified and characterized by a DFT method various stable structures
      with C-Au, C-Au-C, C-Au-H and C-AuH2 types of chemical bonds. The binding
      energies (BE) of C-Au bonds are as high as 227 kJ mol-1 and the bond analysis
      reveals a covalent bonding character. For the experimental detection of these
      structures in gold implanted PE, we predicted characteristic infra-red (IR)
      frequencies. The C-Au stretching vibrational modes lie around 500 cm-1. Other
      characteristic frequencies lie in a band between 730 cm-1 and 1500 cm-1.

PMID- 29057420
TI  - Reply to the 'Comment on "Relating side chain organization of PNIPAm with its
      conformation in aqueous methanol"' by A. Pica and G. Graziano, Soft Matter, 2017,
      13, DOI: 10.1039/C7SM01065F.
AB  - We have recently proposed preferential binding by a cosolvent as the mechanism
      for chain collapse under co-non-solvency. Here we summarise our earlier works and
      provide further evidence that alcohol preferentially binds to PNIPAm, forming
      cosolvent bridges, and thus drives the transition. We also clarify some of the
      common misconceptions evoked in this debate with Pica and Graziano (PG),
      reinforcing the arguments of our earlier reply-comment [Soft Matter, 2017, 13,
      2292] and published works.

PMID- 29057421
TI  - Ion transport mechanisms in lamellar phases of salt-doped PS-PEO block copolymer
      electrolytes.
AB  - We use a multiscale simulation strategy to elucidate, at an atomistic level, the
      mechanisms underlying ion transport in the lamellar phase of polystyrene
      polyethylene oxide (PS-PEO) block copolymer (BCP) electrolytes doped with LiPF6
      salts. Explicitly, we compare the results obtained for ion transport in the
      microphase separated block copolymer melts to those for salt-doped PEO
      homopolymer melts. In addition, we also present results for dynamics of the ions
      individually in the PEO and PS domains of the BCP melt, and locally as a function
      of the distance from the lamellar interfaces. When compared to the PEO
      homopolymer melt, ions were found to exhibit slower dynamics in both the block
      copolymer (overall) and in the PEO phase of the BCP melt. Such results are shown
      to arise from the effects of slower polymer segmental dynamics in the BCP melt
      and the coordination characteristics of the ions. Polymer backbone-ion residence
      times analyzed as a function of distance from the interface indicate that ions
      have a larger residence time near the interface compared to that near the bulk of
      lamella, and demonstrates the influence of the glassy PS blocks and microphase
      segregation on the ion transport properties. Ion transport mechanisms in BCP
      melts reveal that there exist five distinct mechanisms for ion transport along
      the backbone of the chain and exhibit qualitative differences from the behavior
      in homopolymer melts. We also present results as a function of salt concentration
      which show that the mean-squared displacements of the ions decrease with
      increasing salt concentration, and that the ion residence times near the polymer
      backbone increase with increasing salt concentration.

PMID- 29057422
TI  - Modified Measles: A Diagnostic Challenge.

PMID- 29057423
TI  - 9q22.3 Microdeletion Syndrome with Multiple Basal Cell Carcinomas Treated with
      Vismodegib: Three Key Messages in One Patient.

PMID- 29057424
TI  - Late-onset Erythropoietic Protoporphyria Associated with Myelodysplastic Syndrome
      Treated with Azacitidine.

PMID- 29057425
TI  - Cutaneous Chronic Graft Versus Host Disease Following Allogeneic Haematopoietic
      Stem Cell Transplantation in Children: A Retrospective Study.
AB  - Chronic graft versus host disease (cGVHD) is a complication of allogeneic
      haematopoietic stem cell transplantation (HSCT). The aim of this study was to
      clinically characterize childhood cutaneous cGVHD. A retrospective study of
      children treated with HSCT at 2 tertiary medical centres in Israel between 2011
      and 2014 was performed. A total of 112 children were included. Cutaneous cGVHD
      developed in 18% of subjects. Risk factors were older age, HSCT from peripheral
      blood and acute lymphoblastic leukaemia. The eruption was lichenoid in 90% of
      subjects, of whom one-third progressed to sclerosis. Topical treatments were
      usually sufficient in localized disease. Widespread eruption necessitated
      phototherapy, extracorporeal photopheresis and/or systemic immunosuppressants.
      Patients presenting with palmoplantar keratoderma, developed sclerosis. To the
      best of our knowledge, this is the first study describing childhood cutaneous
      cGVHD. Lichenoid eruption is the most common cutaneous pattern of cGVHD in
      children. Sclerotic changes may be associated with prior keratoderma. cGVHD poses
      a therapeutic challenge and better treatments should be sought.

PMID- 29057426
TI  - Chronic Nodular Dermatosis: A Quiz.

PMID- 29057427
TI  - Heterogeneity of Skin Re-innervation After Burns and Factors Involved in its
      Regulation: A Pilot Study.

PMID- 29057428
TI  - Pain Quality Assessment Scale for Epidermolysis Bullosa.
AB  - Pain is one of the most debilitating symptoms in epidermolysis bullosa (EB)
      leading to reduced quality of life. Pain in EB comprises both neuropathic and non
      neuropathic qualities. An assessment of pain qualities has not formerly been
      completed in EB. The Pain Quality Assessment Scale (PQAS) is an adjusted version
      of the validated Neuropathic Pain Scale and includes 20 pain qualities and
      descriptors. Patients with EB (n = 43) rated the pain qualities in the PQAS on 20
      numerical scales and 1 multiple choice question. Pain was experienced by 39
      patients (91%). In general, patients with EB experience intense and unpleasant
      pain on the surface of the skin; the hands and feet are most commonly affected.
      The subtypes, recessive dystrophic EB and junctional EB reported pain qualities
      pathognomonic of neuropathic pain. The PQAS adds value to the current practice of
      global pain intensity scoring in EB.

PMID- 29057429
TI  - Placebo Effects of Open-label Verbal Suggestions on Itch.
AB  - Placebo effects are positive outcomes that are not due to active treatment
      components, which may be elicited even when patients are aware of receiving an
      inert substance (open-label). This proof-of-principle study investigated for the
      first time whether open-label placebo effects on itch can be induced by verbal
      suggestions alone. Ninety-two healthy volunteers were randomized to experimental
      (open-label suggestions) or control (no suggestions) groups. Self-reported itch
      evoked by histamine iontophoresis was the primary study outcome. In addition,
      itch expectations, skin condition and affect were assessed. The experimental
      group expected lower itch than the control group, which was, in turn, related to
      less experienced itch in this group only, although no significantly different
      itch levels were reported between groups. The results illustrate a potential role
      for open-label placebo effects in itch, and suggest that further study of verbal
      suggestions through an extensive explanation of placebo effects might be
      promising for clinical practice.

PMID- 29057430
TI  - Regulation and function of sphingosine kinase 2 in diseases.
AB  - Sphingosine kinase functions to phosphorylate sphingosine to sphingosine 1
      phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are
      two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine
      kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2
      has distinct distribution, regulation and function. SphK2 is involved in the
      pathological processes of varieties of diseases including cancer,
      neurodegenerative disorders, stroke, cardiovascular diseases and inflammation.
      SphK2 may promote the proliferation of cancer cells and the progression of
      inflammation. The SphK2/S1P pathway is also involved in the pathogenesis of
      neurodegenerative disorders and stroke. S1P produced by SphK2 in the nucleus
      binds to HDACs, which then inhibits histone acetylation and regulates memory. The
      SphK2 pathway mediates platelet aggregation, thrombosis, cardioprotection and
      helps to ameliorate hepatic steatosis. This review focuses on the recent advances
      in research on SphK2 regulation and its potential roles in diseases, highlighting
      SphK2 may be a novel therapeutic strategy for diseases.

PMID- 29057431
TI  - Is routine performance of the uterine cervix canal curettage prior to the
      curettage of the uterine cavity justified?
AB  - OBJECTIVES: Endocervical curettage (ECC) together with the dilatation and
      curettage of the uterine cavity (D & C) is routinely performed in everyday
      clinical practice. The aim of this study is to assess the rationale of the
      performance of ECC prior to D & C in indications other than abnormal uterine
      bleeding (AUB). MATERIAL AND METHODS: Case histories of 736 patients after ECC
      performed in the 1st Department of Obstetrics and Gynaecology, Medical University
      of Warsaw, were analyzed retrospectively, the indications for the procedure -
      age, menopausal status, parity, procedure operator's experience - as well as the
      result of the histopathology examination were taken into account. Three groups of
      patients were distinguished based on the indications for the procedure. RESULTS:
      In 645 (87.6%) of cases normal histopathology results were obtained. 40 (5.4%)
      cases were abnormal. 31 cases of uterine cervix dysplasia were disclosed (CIN 1
      20; CIN 2-5; CIN 3-6), 8 cases of endometrial cancer and 1 case of cancer of the
      uterine cervix were disclosed. In 51 (7%) of cases tissue material for
      histopathology examination was not obtained. In patients where ECC and D & C were
      performed due to indications other than abnormal bleeding from uterine cavity, no
      abnormal results were revealed. In addition, in this group the highest number of
      non-diagnostic ECCs was reported (11.59%; p < 0.05). CONCLUSIONS: In the case of
      endometrial biopsy for indications other than AUB routine ECC prior to D & C need
      not be performed.

PMID- 29057432
TI  - Strategy and early results of treatment of advanced cervical cancer patients with
      synchronous cancers observed in PET-CT imaging.
AB  - OBJECTIVES: The aim of this study was to present strategy and early results of
      treatment of advanced cervical cancer patients with synchronous cancers observed
      in PET-CT imaging, treated at the Greater Poland Cancer Center. MATERIAL AND
      METHODS: The study included a group of 200 patients with diagnosed stage IIB-IIIB
      cervical cancer who received PET-CT for the purpose of radiotherapy treatment
      planning. RESULTS: Among our study group, four patients (2%) were found to have a
      synchronous cancer. Two of the cases were diagnosed as breast cancer. However,
      cancers diagnosed in the other two patients were head and neck malignancies -
      hypopharyngeal and laryngeal cancer. The choice of an optimal therapeutic
      approach requires taking into account characteristics of particular malignancies,
      their stage and histopathology. The whole therapy included radiotherapy of
      cervical cancer with various combinations of systemic treatment, radiotherapy or
      surgery of synchronous cancer. According to treatment results, patients diagnosed
      with breast cancer and hypopharyngeal cancer achieved complete remission of both
      primary and secondary tumour. Patient diagnosed with laryngeal malignancy,
      despite achieving complete remission of cervical cancer, finished radiotherapy of
      the synchronous cancer at a palliative dose. CONCLUSIONS: The growing
      availability of PET-CT and other imaging methods in cancer diagnosis will
      increase the number of diagnosed synchronous cancers. Second primary cancers are
      often detected at an early stage, where radical treatment can be performed for
      both primary and secondary tumour. However, treatment of such complicated
      clinical cases as synchronous cancers should be carried out by multidisciplinary
      teams.

PMID- 29057433
TI  - Screening for trisomy 21 based on maternal age, nuchal translucency measurement,
      first trimester biochemistry and quantitative and qualitative assessment of the
      flow in the DV - the assessment of efficacy.
AB  - OBJECTIVES: The aim of the study was to compare effects of addition of two
      methods of ductus venosus (DV) flow assessment: qualitative - the assessment of
      shape of the A-wave (positive or negative), and quantitative - based on the
      pulsatility index for veins (DVPI) to the basic screening for trisomy 21 at 11 to
      13 + 6 weeks of pregnancy. MATERIAL AND METHODS: The ultrasound examination was
      performed in 8230 fetuses in singleton pregnancies at 11- -13 + 6 wks, as a part
      of a routine screening for chromosomal defects. In DV A-wave was assessed and
      DVPI was calculated. After the scan blood sample was taken for first trimester
      biochemistry (BC). Risk for chromosomal defects was calculated and high-risk
      patients were offered an invasive test for karyotyping. RESULTS: Basic screening
      with following combination of markers: MA, NT and BC provided lowest detection
      rate (DR) 87.50% for FPR = 6.94%. After adding qualitative DV A-wave assessment
      DR increased to 88.75% for FPR = 5.65%. The best DR = 93.75% for FPR = 5.55% was
      achieved when quantitative DVPI was added. The application of the Receiver
      Operating Curves curve confirmed validity of the addition of DV flow assessment
      to the screening model. The highest diagnostic power of the test was achieved
      when DVPI was added, with the ROC AUC of 0.974. CONCLUSIONS: The assessment of DV
      flow performed at 11-13 + 6 weeks increases DR for trisomy 21 and reduces FPR.
      The screening model based on the quantitative DV flow analysis (DVPI) gives
      better results compared to the qualitative flow assessment.

PMID- 29057434
TI  - Early vesico-amniotic shunting - does it change the prognosis in fetal lower
      urinary tract obstruction diagnosed in the first trimester?
AB  - OBJECTIVES: The aim of the study was to assess the outcome of vesico-amniotic
      shunting performed before 16 weeks of pregnancy in fetuses with severe megacystis
      diagnosed in the first trimester of pregnancy. MATERIAL AND METHODS: Between
      January 2008 and October 2012 severe megacystis with the bladder length > 15 mm
      was diagnosed in 17 fetuses. The procedure of early vesico-amniotic shunting
      (VAS) was offered to 8 patients with presumably isolated LUTO. The procedure of
      VAS was performed in 6 fetuses. Before the intervention one or two procedures of
      vesicocentesis and urine analysis were performed. RESULTS: In all treated cases
      shunts provided urinary tract decompression. All babies were born prematurely, 2
      of them died due to premaurity, 3 of them survived and have normal renal function
      at the age of 5-6 years. In 4/5 children accompanying malformations were later
      diagnosed, in 1 born prematurely neonate necropsy was not performed. CONCLUSIONS:
      Our results suggest that early vesico-amniotic shunting in fetal LUTO is feasible
      and may potentially prevent not only pulmonary hypoplasia but also renal
      insufficiency. However, the rationale of the procedure needs further
      investigation due to a high risk of long-term morbidity and co-existing
      malformations in children Before offering the therapy detailed counseling of the
      parents about the possible pros and cons of the therapy is necessary.

PMID- 29057435
TI  - Influence of first trimester biochemistry methodology on detection rate in
      screening for trisomy 21.
AB  - OBJECTIVES: The purpose of the study was to compare detection rates (DR) of FMF
      certified and non-certified biochemical tests (BC) in trisomy 21 screening at 11
      13 + 6 weeks. MATERIAL AND METHODS: In 2267 singleton pregnancies FMF-certified
      doctors measured crown to rump length (CRL) and nuchal translucency (NT). Serum
      samples were tested for free beta-hCG and the PAPP-A using 2 analysers (Delfia -
      Perkin Elmer and Immulite 2000 - DPC), the results were expressed in MoM values
      and used for computer calculation of the risk for trisomy 21. The cut-off value
      for the high trisomy 21 risk was 1:300. RESULTS: Comparison of free beta-hCG MoMs
      by DPC and Delfia demonstrated statistically significant differences in normal,
      and trisomy 21 fetuses respectively. Similarly, statistically significant
      differences were noted for PAPP-A MoMs. The above differences in MoMs resulted in
      altered sensitivity in screening for aneuploidy. The application of the FMF
      certified method ensures a markedly higher DR = 74%, compared to non-certified
      tests (64%), both at 5% FPR. The ROC analysis was performed in order to assess
      the efficacy of both tests. Results of trisomy 21 BC + NT risk scales using the
      Delfia and DPC methods are highly significant (p < 0.0001), which means that
      their discrimination ability is > 90%. The difference between results obtained
      using the Delfia and DPC methods is AUC = 0.0150 and is statistically significant
      (Z = 2.4728, p = 0.0134). CONCLUSIONS: The use of FMF-certified first trimester
      biochemistry analysers improves DR for trisomy 21. The use of non-certified
      analysers causes reduction of DR and an increase of invasive procedure rate.

PMID- 29057436
TI  - Non-invasive therapeutic use of High-Intensity Focused Ultrasound (HIFU) with 3
      Tesla Magnetic Resonance Imaging in women with symptomatic uterine fibroids.
AB  - Benign uterine fibroids are common female genital tract tumors and if symptomatic
      often require extensive surgery. When tumors are multiple and large or unusually
      located, the operative treatment may lead to significant morbidity and compromise
      quality of life. Recovery period after surgical treatment may be complicated by
      patient's medical condition and wound healing problems. Currently used other non
      surgical treatment modalities usually provide only a temporal symptoms relief and
      may not be efficient in all affected women. In the last decade, minimally
      invasive treatment of uterine fibroids called Magnetic Resonance guided High
      Intensity Focused Ultrasound (MRI HIFU) was introduced. This technique uses
      thermal ablation simultaneously with MRI imaging of the mass and tissue
      temperature measurements during the procedure where a focused ultrasound beam is
      applied externally to destroy tumors located in the human body. Successful
      application of MRI HIFU has been recently described in patients with various
      malignancies, such as breast, prostate and hepatocellular cancers as well as soft
      tissue and bone tumors. This technique is innovative and has been proven to be
      safe and effective but there are several limitations for treatment. The article
      highlights the relative advantages and disadvantages of MRI guided HIFU in women
      with uterine fibroids. The authors also describe high-resolution MRI technique on
      3T MRI, along with the approach to interpretation of HIFU results applied to
      uterine fibroids that has been experienced at one institution.

PMID- 29057437
TI  - Perspectives for the pharmacological treatment of overactive bladder syndrome.
AB  - It has been found that antimuscarinic drugs, viewed as the "gold standard" in
      overactive bladder syndrome (OAB) treatment, have an unsatisfactory tolerance
      profile and limited clinical effectiveness. This fact has given a clear impetus
      to search for new options in OAB pharmacotherapy. The conducted pre-clinical
      trials have led to the development of new solutions for the treatment of OAB,
      which stand a good chance of being applied in clinical practice. The said
      compounds are characterised by higher receptor and organ specificity than
      currently used medications.

PMID- 29057439
TI  - Prenatal and postnatal detection of congenital heart diseases.
AB  - Congenital heart defects are among the most common birth defects and represent a
      major challenge in prenatal diagnosis and therapy of a newborn.

PMID- 29057438
TI  - Selected trace elements concentrations in pregnancy and their possible role -
      literature review.
AB  - The aim of this study was to review the role of selected trace elements in
      pregnancy and fetal development. Citations related to the role of iron (Fe), zinc
      (Zn), manganese (Mn), copper (Cu) and selenium (Se) during pregnancy were
      searched in PubMed, Medline, Web of Science, using keywords and MeSH terms.
      Inadequate supply of trace elements can cause abnormalities of fetal development
      and predispose a child to disorders later on in life. Trace elements are the key
      elements of complex enzymes responsible for the modulation of the antioxidant
      defense system of the organism. It has been suggested that there is a correlation
      between reduced levels of trace elements essential for antioxidant function in
      the body of pregnant women, and an increased risk of developing preeclampsia.
      Trace elements are components of numerous regulatory enzymes and hormones
      essential to the division and differentiation of fetal cells and their further
      development. Mineral deficiencies in pregnant women can cause birth defects of
      the central nervous system, and growth disorders. Future research should be
      directed to explain the interaction between trace elements, and establish the
      optimum levels of macro and micronutrients supplementation, as well as determine
      the reference values for trace elements in the maternal serum, umbilical cord
      blood and amniotic fluid.

PMID- 29057440
TI  - Percutaneous closure of atrial septal defect type II - a few remarks on the basis
      of my own experience.

PMID- 29057441
TI  - Repetitive stent thrombosis: another manifestation of Kounis syndrome?

PMID- 29057443
TI  - Holographic imaging during transcatheter aortic valve implantation procedure in
      bicuspid aortic valve stenosis.

PMID- 29057442
TI  - [Subcutaneous implantable cardioverter-defibrillator in prevention of sudden
      cardiac death in Poland - opinion paper endorsed by the Polish Cardiac Society
      Working Group on Heart Rhythm].
AB  - In the past years, cardiovascular mortality has decreased but despite these
      cardiovascular diseases are responsible for millions of deaths every year in the
      world and approximately 25% of which are sudden cardiac death (SCD). Implantable
      defibrillators (ICD) is proven therapy used in primary and secondary SCD
      prevention. Currently majority of devices use transvenous leads inserted
      predominantly into the right heart for both pacing and defibrillation. On the
      other hand, ICD may cause complica-tions, including inappropriate shocks, device
      related infection and lead failure. Problems with transvenous leads prompted the
      development of a subcutaneous defibrillator (S-ICD) with an electrode system that
      is placed entirely subcutaneously, outside the thoracic cavity. The device may be
      useful when venous access is difficult, in young patients and in patients at
      particular risk of infection. S-ICD is not suitable for patients with indications
      for bradycardia pacing, cardiac resynchronisation therapy and in cases with
      tachyarrhythmia easily terminated by antitachycardia pacing.

PMID- 29057444
TI  - Subcutaneous cardioverter-defibrillator in a young male with heart failure and
      chronic kidney disease - complexity of clinical decisions in everyday practice.

PMID- 29057445
TI  - Intravascular uplift of an occlusive spiral dissection using a hi-torque PILOT
      150 guidewire for successful entry of the true right coronary artery lumen.

PMID- 29057446
TI  - Aortoesophageal aneurysmal sac and aorto-left pleural fistula - a rare
      complication of aortic aneurysm.

PMID- 29057447
TI  - Hybrid approach for complicated Type B aortic dissection.

PMID- 29057448
TI  - Extensive myocardial infarction in a 20-year-old associated with diabetic
      ketoacidosis.

PMID- 29057449
TI  - Efficacy and tolerability of mexiletine treatment in patients with recurrent
      ventricular tachyarrhythmias and implantable cardioverter-defibrillator shocks.
AB  - BACKGROUND: Antiarrhythmic treatment of patients with recurrent ventricular
      tachyarrhythmia, in whom catheter ablation and amiodarone treatment were
      ineffective or contraindicated, is an unsolved clinical problem. AIM: The study
      aims to evaluate the efficacy and tolerability of mexiletine in patients with
      recurrent ventricular tachyarrhythmias and/or electrical storm events, in whom
      standard treatment strategies failed to prevent ventricular tachyarrhythmia.
      METHODS: We performed a retrospective cohort analysis of all patients treated
      with mexiletine for recurrent ventricular tachycardia and/or ventricular
      fibrillation in our institution between January 2011 and September 2015. The
      primary endpoints were total number of electrical storm events and ventricular
      tachycardia/ventricular fibrillation (VT/VF) episodes after the beginning of
      mexiletine therapy. Secondary endpoints were total number of implantable
      cardioverter-defibrillator (ICD) therapies and discontinuation of the therapy.
      Events were compared with a matched duration period before initiating mexiletine.
      Patients served as self-controls. RESULTS: Seventeen patients were included in
      the study; 11 patients were males. Mean age was 64.2 +/- 15.4 years. The median
      time of mexiletine treatment was eight months (interquartile range [IR]: 1-22
      months). The mexiletine dose was 600 mg/day in 13 patients and 400 mg/day in four
      patients. In four patients the dose was modified during treatment in a range from
      400 to 600 mg/day depending on clinical decision. Treatment with mexiletine
      significantly reduced the number of electrical storm events (14 episodes vs. two
      episodes; median and IR for 17 patients: 1 [0-1] vs. 0 [0-0], p = 0.0010), VT/VF
      episodes (285 vs. 74 episodes; median and IR for 17 patients: 7 [5-27] vs. 0 [0
      5], p = 0.0115), and ICD interventions (317 interven-tions vs. nine
      interventions; median and IR for 17 patients: 10 [5-25] vs. 0 [0-2], p = 0.0006),
      in comparison with a matched period before initiation of treatment. In 14 out of
      17 patients (82%) sufficient tolerability of mexiletine was observed. Only in
      three (18%) patients severe side effects of mexiletine treatment occurred
      requiring discontinuation of therapy. CONCLUSIONS: Mexiletine was a sufficiently
      tolerated antiarrhythmic drug in short-term treatment of ventricular tachyarrhyth
      mias in the studied population. Mexiletine may be effective in the treatment of
      recurring ventricular tachyarrhythmias or electrical storm events.

PMID- 29057451
TI  - Angiolymphoid hyperplasia with eosinophilia: report of nine cases.
AB  - BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign
      vascular proliferation characterized by dermal or subcutaneous red or brown
      papules or nodules, most commonly on the head and neck. OBJECTIVE: The aim of
      this study was to review the epidemiological and clinical characteristics of
      ALHE, focusing particularly on the histological and therapeutic features.
      METHODS: We performed a retrospective study of all cases of ALHE diagnosed in our
      dermatology and pathology departments between 2004 and 2015. RESULTS: Over 12
      years, we collected nine cases of ALHE (0.75 case/year). There were four men and
      five women. The mean age was 43 years. Lesions presented as erythematous or
      violaceous papules or nodules in all cases, multiple in five cases, and localized
      on the head in eight cases or other sites in four cases. The diagnosis of ALHE
      was clinically suspected in only two cases. The histopathological findings showed
      an ill-circumscribed, intradermal slightly lobular proliferation of capillary
      sized vessels around several central vessels. In all cases, the blood vessels
      were lined by large endothelial cells. An inflammatory infiltrate around the
      vessels was formed mainly of lymphocytes and eosinophils with isolated plasma
      cells and histiocytes. Surgery was the most common treatment in our series. Other
      local or general treatment has also been used with varying responses. CONCLUSION:
      Angiolymphoid hyperplasia with eosinophilia is a rare epithelioid vascular tumor
      with a challenging clinical and histological diagnosis. Despite its benign
      nature, ALHE causes a therapeutic dilemma.

PMID- 29057452
TI  - Is unconsciousness simply the reverse of consciousness?

PMID- 29057450
TI  - The relationship between physical and psychological symptoms and health care
      utilization in hospitalized patients with advanced cancer.
AB  - BACKGROUND: Patients with advanced cancer often experience frequent and prolonged
      hospitalizations; however, the factors associated with greater health care
      utilization have not been described. We sought to investigate the relation
      between patients' physical and psychological symptom burden and health care
      utilization. METHODS: We enrolled patients with advanced cancer and unplanned
      hospitalizations from September 2014-May 2016. Upon admission, we assessed
      physical (Edmonton Symptom Assessment System [ESAS]) and psychological symptoms
      (Patient Health Questionnaire 4 [PHQ-4]). We examined the relationship between
      symptom burden and healthcare utilization using linear regression for hospital
      length of stay (LOS) and Cox regression for time to first unplanned readmission
      within 90 days. We adjusted all models for age, sex, marital status, comorbidity,
      education, time since advanced cancer diagnosis, and cancer type. RESULTS: We
      enrolled 1,036 of 1,152 (89.9%) consecutive patients approached. Over one-half
      reported moderate/severe fatigue, poor well being, drowsiness, pain, and lack of
      appetite. PHQ-4 scores indicated that 28.8% and 28.0% of patients had depression
      and anxiety symptoms, respectively. The mean hospital LOS was 6.3 days, and the
      90-day readmission rate was 43.1%. Physical symptoms (ESAS: unstandardized
      coefficient [B], 0.06; P < .001), psychological distress (PHQ-4 total: B, 0.11; P
      = .040), and depression symptoms (PHQ-4 depression: B, 0.22; P = .017) were
      associated with longer hospital LOS. Physical (ESAS: hazard ratio, 1.01; P <
      .001), and anxiety symptoms (PHQ-4 anxiety: hazard ratio, 1.06; P = .045) were
      associated with a higher likelihood for readmission. CONCLUSIONS: Hospitalized
      patients with advanced cancer experience a high symptom burden, which is
      significantly associated with prolonged hospitalizations and readmissions.
      Interventions are needed to address the symptom burden of this population to
      improve health care delivery and utilization. Cancer 2017;123:4720-4727. (c) 2017
      American Cancer Society.

PMID- 29057455
TI  - Unusual location of a common dermatosis.

PMID- 29057453
TI  - 5-HT1F receptor-mediated mitochondrial biogenesis for the treatment of
      Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Parkinson's disease is characterized by progressive
      decline in motor function due to degeneration of nigrostriatal dopaminergic
      neurons, as well as other deficits including cognitive impairment and behavioural
      abnormalities. Mitochondrial dysfunction, leading to loss of ATP-dependent
      cellular functions, calcium overload, excitotoxicity and oxidative stress, is
      implicated in the pathophysiology of Parkinson's disease. Using the 5-HT1F
      receptor agonist LY344864, a known inducer of mitochondrial biogenesis (MB), we
      investigated the therapeutic efficacy of stimulating MB on dopaminergic neuron
      loss in a mouse model of Parkinson's disease. EXPERIMENTAL APPROACH: Male C57BL/6
      mice underwent bilateral intrastriatal 6-hydroxydopamine or saline injections and
      daily treatment with 2 mg.kg-1 LY344864 or vehicle for 14 days beginning 7 days
      post-lesion. Tyrosine hydroxylase immunoreactivity (TH-ir) and MB were assessed
      in the brains of all groups following treatment, and locomotor activity was
      evaluated prior to lesioning, 7 days post-lesion and after treatment. KEY
      RESULTS: Increased mitochondrial DNA content and nuclear- and mitochondrial
      encoded mRNA and protein expression was observed in specific brain regions of
      LY344864-treated naive and lesioned mice, indicating augmented MB. LY344864
      attenuated TH-ir loss in the striatum and substantia nigra compared to vehicle
      treated lesioned animals. LY344864 treatment also increased locomotor activity in
      6-hydroxydopamine lesioned mice, while vehicle treatment had no effect.
      CONCLUSIONS AND IMPLICATIONS: These data revealed that LY344864-induced MB
      attenuates dopaminergic neuron loss and improves behavioural endpoints in this
      model. We suggest that stimulating MB may be beneficial for the treatment of
      Parkinson's disease and that the 5-HT1F receptor may be an effective therapeutic
      target.

PMID- 29057454
TI  - Cannabidiolic acid methyl ester, a stable synthetic analogue of cannabidiolic
      acid, can produce 5-HT1A receptor-mediated suppression of nausea and anxiety in
      rats.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to compare the abilities of
      cannabidiolic acid methyl ester (HU-580) and cannabidiolic acid (CBDA) to enhance
      5-HT1A receptor activation in vitro and produce 5-HT1A -mediated reductions in
      nausea and anxiety in vivo. EXPERIMENTAL APPROACH: We investigated the effects of
      HU-580 and CBDA on (i) activation by 8-hydroxy-2-(di-n-propylamino)tetralin of
      human 5-HT1A receptors in CHO cell membranes, using [35 S]-GTPgammaS binding
      assays, (ii) gaping by rats in acute and anticipatory nausea models, and (iii)
      stress-induced anxiety-like behaviour, as indicated by exit time from the light
      compartment of a light-dark box of rats subjected 24 h earlier to six tone-paired
      foot shocks. KEY RESULTS: HU-580 and CBDA increased the Emax of 8-hydroxy-2-(di-n
      propylamino) tetralin in vitro at 0.01-10 and 0.1-10 nM, respectively, and
      reduced signs of (i) acute nausea at 0.1 and 1 MUg.kg-1 i.p. and at 1 MUg.kg-1
      i.p., respectively, and (ii) anticipatory nausea at 0.01 and 0.1 MUg.kg-1 , and
      at 0.1 MUg.kg-1 i.p. respectively. At 0.01 MUg.kg-1 , HU-580, but not CBDA,
      increased the time foot-shocked rats spent in the light compartment of a light
      dark box. The anti-nausea and anti-anxiety effects of 0.01 or 0.1 MUg.kg-1 HU-580
      were opposed by the 5-HT1A antagonist, WAY100635 (0.1 mg.kg-1 i.p.). CONCLUSIONS
      AND IMPLICATIONS: HU-580 is more potent than CBDA at enhancing 5-HT1A receptor
      activation, and inhibiting signs of acute and anticipatory nausea, and anxiety.
      Consequently, HU-580 is a potential medicine for treating some nausea and anxiety
      disorders and possibly other disorders ameliorated by enhancement of 5-HT1A
      receptor activation.

PMID- 29057456
TI  - Small fetal thymus and adverse obstetrical outcome: a systematic review and a
      meta-analysis.
AB  - INTRODUCTION: The aim of this study was to explore the association between small
      fetal thymus on ultrasound and adverse obstetrical outcome. MATERIAL AND METHODS:
      Medline, Embase, Cochrane and Web of Science databases were searched. Primary
      outcome was the risk of preterm birth before 37 and 34 weeks of gestation in
      fetuses with, compared to those without, a small thymus on ultrasound. SECONDARY
      OUTCOMES: occurrence of chorioamnionitis, intrauterine growth restriction,
      neonatal sepsis, gestational age at birth, birthweight, neonatal morbidity and
      preeclampsia. RESULTS: Twelve studies including 1744 fetuses who had ultrasound
      assessment of thymus during pregnancy were included. Women with preterm premature
      rupture of the membranes or with preterm labor were at higher risk of preterm
      birth before 37 weeks (p = 0.01), or before 34 weeks (p < 0.001) for fetuses with
      a small fetal thymus compared to those without a small thymus, and the risk of
      chorioamnionitis was higher when the thymus was small (p < 0.001). Fetuses with
      small thymus were not at higher risk of intrauterine growth restriction (p =
      0.3). A small thymus increased the risk of neonatal sepsis (p = 0.007) and
      morbidity (p = 0.003), but not the risk of preeclampsia (p = 0.9). CONCLUSIONS: A
      small fetal thymus is associated with a higher risk of preterm birth,
      chorioamnionitis, neonatal sepsis and morbidity, but not with intrauterine growth
      restriction and preeclampsia.

PMID- 29057458
TI  - Support needs of people living with Mycobacterium ulcerans (Buruli ulcer) disease
      in a Ghana rural community: a grounded theory study.
AB  - INTRODUCTION/BACKGROUND: Mycobacterium ulcerans (also known as Buruli ulcer)
      disease is a rare skin disease which is prevalent in rural communities in the
      tropics mostly in Africa. Mortality rate is low, yet morbidity and consequent
      disabilities affect the quality of life of sufferers. AIMS: The aim of this paper
      is to use the grounded theory method to explore the support needs of people
      living with the consequences of Buruli ulcer in an endemic rural community in
      Ghana. METHODS: We used the grounded theory research approach to explore the
      experiences of people living with Mycobacterium ulcerans in a rural district in
      Ghana and provide a basis to understand the support needs of this group. RESULTS:
      The key support needs identified were: functional limitations, fear and frequency
      of disease recurrence, contracture of limbs and legs, loss of sensation and
      numbness in the affected body area, lack of information from health professionals
      about self-care, feeling tired all the time, insomnia, lack of good diet, lack of
      access to prostheses, having to walk long distances to access health services,
      and loss of educational opportunities. DISCUSSIONS: The study discusses how the
      systematically derived qualitative data has helped to provide a unique insight
      and advance our understanding of the support needs of people living with BU and
      how they live and attempt to adapt their lives with disability. We discuss how
      the availability of appropriate interventions and equipment could help them self
      manage their condition and improve access to skin care services. CONCLUSIONS: The
      support needs of this vulnerable group were identified from a detailed analysis
      of how those living with BU coped with their lives. A key issue is the lack of
      education to assist self-management and prevent deterioration. Further research
      into the evaluation of interventions to address these support needs is necessary
      including self-management strategies.

PMID- 29057459
TI  - Phone calls to an Australian pregnancy and lactation counselling service
      regarding use of galactagogues during lactation - the MotherSafe experience.
AB  - Galactagogues represent substances used to enhance breast milk production.
      Between 2001 and 2014 we identified 2034 phone calls regarding the use of
      galactagogues made to MotherSafe. The majority involved discussion of domperidone
      (n = 1884; 92.6%), with the remainder relating to metoclopramide (n = 153; 7.5%)
      or other herbal galactagogues (eg fenugreek, milk thistle; n = 262; 12.9%). A 50%
      decrease in total calls occurred from 2011 to 2014, while the percentage of calls
      regarding herbal galactagogues increased from 0% in 2001 to 23% in 2014. These
      findings support the need for more robust research surrounding the use of
      galactagogues in clinical practice.

PMID- 29057457
TI  - Differential effects of selective agonists of neuromedin U1 and U2 receptors in
      obese and diabetic mice.
AB  - BACKGROUND AND PURPOSE: Neuromedin U (NmU) may be a novel target for obesity
      treatment owing to its anorectic and energy expenditure enhancing effects.
      Although two receptors, NMU1 and NMU2, are both responsible for the NmU-mediated
      anti-obesity effects, the receptor agonist with the most appropriate profiles for
      treating obesity and diabetes in terms of efficacy and safety is as yet unknown.
      Thus, we developed and evaluated novel NMU1/2 receptor-selective agonists.
      EXPERIMENTAL APPROACH: Efficacy and safety were assessed in mice with diet
      induced obesity (DIO) and those with leptin-deficient diabetes (ob/ob) through
      repeated peripheral administration of selective agonists to NMU1 (NMU-6102) and
      NMU2 (NMU-2084), along with non-selective NMU1/2 agonists (NMU-0002 and NMU
      6014). We also performed immunohistochemistry for c-Fos protein expression in the
      brain to probe their mechanisms of action. KEY RESULTS: Although both non
      selective NMU1/2 agonists and the NMU2-selective agonist had high efficacy
      compared with the NMU1-selective agonist, only the NMU2-selective agonist led to
      relatively low adverse effects, such as diarrhoea, in DIO mice. However, the non
      selective NMU1/2 agonist and the NMU1-selective agonist, but not the NMU2
      selective agonist, were effective in diabetic ob/ob mice. Mechanistically, NMU2
      selective agonists preferentially activate pro-opiomelanocortin neurons in the
      hypothalamic arcuate nucleus but not in the paraventricular nucleus. CONCLUSIONS
      AND IMPLICATIONS: These results suggest that an NMU2 receptor-selective agonist
      may be a well-balanced drug for the treatment of obesity and that an NMU1
      receptor-selective agonist may also be beneficial for treating obesity and
      diabetes once its side effects are minimized.

PMID- 29057460
TI  - Psoriasis and small intestine bacterial overgrowth.

PMID- 29057461
TI  - Clinical Guidelines for Working With Stepfamilies: What Family, Couple,
      Individual, and Child Therapists Need to Know.
AB  - This article draws on four decades of research and clinical practice to delineate
      guidelines for evidence-informed, clinically sound work with stepfamilies for
      couple, family, individual adult, and child therapists. Few clinicians receive
      adequate training in working with the intense and often complex dynamics created
      by stepfamily structure and history. This is despite the fact that stepfamilies
      are a fundamentally different family form that occurs world-wide. As a result
      many clinicians rely on their training in first-time family models. This is not
      only often unhelpful, but all too often inadvertently destructive. The article
      integrates a large body of increasingly sophisticated research about stepfamilies
      with the author's four decades of clinical practice with stepfamily
      relationships. It describes the ways in which stepfamilies are different from
      first-time families. It delineates the dynamics of five major challenges
      stepfamily structure creates: (1) Insider/outsider positions are intense and they
      are fixed. (2) Children struggle with losses, loyalty binds, and change. (3)
      Issues of parenting, stepparenting, and discipline often divide the couple. (4)
      Stepcouples must build a new family culture while navigating previously
      established family cultures. (5) Ex-spouses (other parents outside the household)
      are part of the family. Some available data are shared on the impact of cultural
      and legal differences on these challenges. A three-level model of clinical
      intervention is presented: Psychoeducational, Interpersonal, and
      Intrapsychic/Intergenerational Family-of-Origin. The article describes some "easy
      wrong turns" for well-meaning therapists and lists some general clinical
      guidelines for working with stepfamily relationships.

PMID- 29057462
TI  - Insulin-like growth factor-1 activates PI3K/Akt signalling to protect human
      retinal pigment epithelial cells from amiodarone-induced oxidative injury.
AB  - BACKGROUND AND PURPOSE: Amiodarone is one of the most effective anti-arrhythmic
      drugs available, but its clinical applications are limited by toxic side effects
      including optic toxicity. The purpose of this study was to investigate the toxic
      effect of amiodarone on D407 cells (a human retinal pigmented epithelial (RPE)
      cell line) and the mechanisms of the protective effect of insulin-like growth
      factor-1 (IGF-1). EXPERIMENTAL APPROACH: The involvement of the kinases, Akt and
      ERK, was analysed by Western blot. Intracellular accumulation of ROS was measured
      using fluorophotometric quantification. A pharmacological approach with
      inhibitors was used to investigate the pathways involved in the protective action
      of IGF-1. KEY RESULTS: Amiodarone concentration-dependently augmented the
      production of ROS, lipid peroxidation and apoptosis in D407 cells. IGF-1 time-
      and concentration-dependently reversed these effects of amiodarone and protected
      D407 cells from amiodarone-mediated toxicity. Amiodarone inhibited the pAkt but
      not pErk, and IGF-1 reversed this inhibitory effect of amiodarone. However, IGF-1
      failed to suppress amiodarone-induced cytotoxicity in the presence of PI3K/Akt
      inhibitor LY294002 suggesting the direct involvement of the PI3K/Akt pathway.
      Furthermore, in vivo rat flash electroretinogram (FERG) recordings showed that
      IGF-1 reverses the amiodarone-induced decrease in a- and b-waves. The
      immunocytochemistry findings confirmed that vitreous IGF-1 injections promote the
      survival of RPE cells in rat retina treated with amiodarone. CONCLUSION AND
      IMPLICATIONS: IGF-1 can protect RPE cells from amiodarone-mediated injury via the
      PI3K/Akt pathway in vivo and in vitro. IGF-1 has potential as a protective drug
      for the prevention and treatment of amiodarone-induced optic toxicity.

PMID- 29057464
TI  - Successful treatment of refractory cholinergic urticaria with omalizumab.

PMID- 29057463
TI  - ALK-positive primary cutaneous anaplastic large cell lymphoma: a case report and
      review of the literature.
AB  - Anaplastic large cell lymphoma (ALCL) limited to the skin is a distinct disease
      that is designated primary cutaneous ALCL (pcALCL). It has an indolent course
      with a significantly better prognosis compared to systemic ALCL (sALCL).
      Anaplastic lymphoma kinase (ALK) expression in lesions of cutaneous ALCL is
      classically considered to be a marker for skin involvement by sALCL. However,
      recent reports of patients with ALK-positive pcALCL challenge this concept and
      raise prognostic and therapeutic dilemmas. Herein, we report a case of ALK
      positive pcALCL in a 45-year-old woman who was treated with local radiotherapy.
      We review previously reported cases in the literature to better characterize this
      rare variant. Overall, the rates of cutaneous recurrence, systemic dissemination,
      and disease-related mortality in ALK-positive pcALCL do not differ from those
      previously reported in pcALCL. ALK-positive pcALCL is diagnosed at younger age
      and has a better disease course in children compared to adults with lower
      incidences of skin recurrence and progression to systemic disease. We conclude
      that ALK-positivity in cutaneous ALCL does not necessarily imply systemic
      disease. ALK-positive pcALCL has an excellent prognosis and should be treated by
      excision and/or radiotherapy. However, patients must remain under close long-term
      follow-up as recurrence and progression to systemic disease may occur.

PMID- 29057465
TI  - Dermoscopic features of Orf disease.

PMID- 29057466
TI  - A 71-year-old man with a hemorrhagic vesicular eruption.

PMID- 29057468
TI  - Parent-Child Attunement Moderates the Prospective Link between Parental
      Overcontrol and Adolescent Adjustment.
AB  - Parental overcontrol (OC), behavior that intrusively or dominantly restricts
      child autonomy, has been identified as a transdiagnostic risk factor for youth.
      However, it is as yet unknown whether the association between parental OC and
      child maladjustment remains even when OC is exerted infrequently or by attuned
      parents. Rather, the selective use of OC might steer children away from danger.
      Taking a developmental psychopathology approach, this study focuses on the larger
      parent-child relationship context, testing whether either the dose at which
      parents demonstrate OC or the degree to which children perceive their parents as
      attuned determines whether OC is risky or protective for adolescents' adjustment.
      Among a community sample of 114 families of children followed from the ages of 12
      18, we examine whether OC, behaviorally coded from triadic mother-father-child
      discussions in middle childhood, is associated with later risky behavior and
      anxiety symptoms in adolescence. Overcontrol exerted by either mothers or fathers
      had a curvilinear effect on adolescent risky behaviors, and this effect was
      moderated by children's perceived attunement. Although OC generally was
      associated with increased risky behaviors, low doses of OC or OC exerted by
      highly attuned parents protected against engagement in risky behaviors. No main
      effect of OC was observed on adolescent anxiety; however, mothers' OC interacted
      with perceived parental attunement, such that OC exerted by less attuned parents
      predicted greater anxiety. Results underscore that the effect of parenting
      behaviors depends on the larger parent-child relationship context.

PMID- 29057467
TI  - Vortioxetine exerts anti-inflammatory and immunomodulatory effects on human
      monocytes/macrophages.
AB  - BACKGROUND AND PURPOSE: A crosstalk between the immune system and depression has
      been postulated, with monocytes/macrophages and cytokines having a key role in
      this interaction. In this study, we examined whether vortioxetine, a multimodal
      anti-depressive drug, was endowed with anti-inflammatory and antioxidative
      activity, leading to immunomodulatory effects on human monocytes and macrophages.
      EXPERIMENTAL APPROACH: Human monocytes were isolated from buffy coats and used as
      such or differentiated into M1 and M2 macrophages. Cells were treated with
      vortioxetine before or after differentiation, and their responsiveness was
      evaluated. This included oxy-radical and TNFalpha production, TNFalpha and
      PPARgamma gene expression and NF-kappaB translocation. KEY RESULTS: Vortioxetine
      significantly reduced the PMA-induced oxidative burst in monocytes and in
      macrophages (M1 and M2), causing a concomitant shift of macrophages from the M1
      to the M2 phenotype, demonstrated by a significant decrease in the expression of
      the surface marker CD86 and an increase in CD206. Moreover, treatment of
      monocytes with vortioxetine rendered macrophages derived from this population
      less sensitive to PMA, as it reduced the oxidative burst, NF-kB translocation,
      TNFalpha release and expression while inducing PPARgamma gene expression. FACS
      analysis showed a significant decrease in the CD14+ /CD16+ /CD86+ M1 population.
      CONCLUSIONS AND IMPLICATIONS: These results demonstrate that in human
      monocytes/macrophages, vortioxetine has antioxidant activity and anti
      inflammatory effects driving the polarization of macrophages towards their
      alternative phenotype. These findings suggest that vortioxetine, alongside its
      antidepressive effect, may have immunomodulatory properties.

PMID- 29057469
TI  - Beyond "Lots of Hugs and Kisses": Expressions of Parental Love From Parents and
      Their Young Children in Two-Parent, Financially Stable Families.
AB  - Given that parental love is essential for children's optimal development, the
      current study gathered examples of how parental love was demonstrated within
      parent-child relationships. Fifty-eight two-parent, financially stable families
      consisting of a mother, father, and young child (3-7 years old) from the Midwest
      were interviewed regarding how they demonstrated or perceived parental love.
      Results from an inductive thematic analysis revealed considerable variability in
      how parental love was demonstrated, with five themes emerging that overlapped
      between parents and their children: playing or doing activities together,
      demonstrating affection, creating structure, helping or supporting, and giving
      gifts or treats. Some gendered patterns among these themes were found with
      mothers emphasizing physical and verbal affection and fathers highlighting their
      more prominent role as playmates. The lay examples provided by parents and
      children in this exploratory study extend previous conceptualizations of parental
      love and underscore the importance of parents being attuned and responsive to the
      specific needs of their children.

PMID- 29057470
TI  - Origin and evolution of chloroplast group I introns in lichen algae.
AB  - The history of group I introns is characterized by repeated horizontal transfers,
      even among phylogenetically distant species. The symbiogenetic thalli of lichens
      are good candidates for the horizontal transfer of genetic material among
      distantly related organisms, such as fungi and green algae. The main goal of this
      study was to determine whether there were different trends in intron distribution
      and properties among Chlorophyte algae based on their phylogenetic relationships
      and living conditions. Therefore, we investigated the occurrence, distribution
      and properties of group I introns within the chloroplast LSU rDNA in 87
      Chlorophyte algae including lichen and free-living Trebouxiophyceae compared to
      free-living non-Trebouxiophyceae species. Overall, our findings showed that there
      was high diversity of group I introns and homing endonucleases (HEs) between
      Trebouxiophyceae and non-Trebouxiophyceae Chlorophyte algae, with divergence in
      their distribution patterns, frequencies and properties. However, the differences
      between lichen Trebouxiophyceae and free-living Trebouxiophyceae were smaller. An
      exception was the cL2449 intron, which was closely related to omega elements in
      yeasts. Such introns seem to occur more frequently in lichen Trebouxiophyceae
      compared to free-living Trebouxiophyceae. Our data suggest that lichenization and
      maintenance of lichen symbiosis for millions of years of evolution may have
      facilitated horizontal transfers of specific introns/HEs between symbionts. The
      data also suggest that sequencing of more chloroplast genes harboring group I
      introns in diverse algal groups may help us to understand the group I intron/HE
      transmission process within these organisms.

PMID- 29057471
TI  - Delta-like 2 negatively regulates chondrogenic differentiation.
AB  - Delta-like 2 (Dlk2), a glycoprotein highly homologous to Dlk1, belongs to the
      Notch/Delta/Serrata family. Dlk2 has been shown to be an important regulator of
      adipogenesis; however, its role in other cellular differentiation processes is
      still unknown. Therefore, in this study, we aimed to determine the role of Dlk2
      in chondrogenic differentiation. We found that Dlk2 overexpression promoted the
      growth of ATDC5 cells but inhibited insulin-induced ATDC5 chondrogenic
      differentiation, as supported by the reduction in cartilage matrix formation and
      gene expression of aggrecan (acan), collagentype II (col2a1) and X (col10a1). In
      contrast, Dlk2 silencing inhibited the proliferation of ATDC5 cells but enhanced
      their chondrogenic differentiation. We then evaluated the roles of mitogen
      activated protein kinases (MAPKs), which are activated by insulin during the
      chondrogenesis of ATDC5 cells. Overexpression of Dlk2 protein strongly promoted
      the activation of p38, but not extracellular signal-regulated kinase (ERK) 1/2
      and c-Jun N-terminal kinase (JNK). Moreover, as expected, Dlk2 silencing
      inhibited the activation of p38, but had no effect on the ERK1/2 and JNK
      pathways. Finally, we also detected the expression of Dlk2 in mouse epiphyseal
      cartilage during embryo development. The expression of the Dlk2 protein in the
      limb bud could be detected at embryonic day 11.5; additionally, it was found to
      decrease in the superficial zones, but remained unchanged in the
      deep/hypertrophic zones. In conclusion, our results suggested that Dlk2 acted as
      an important regulator of chondrogenesis through the p38 pathway. These findings
      may lead to strategies for the treatment of cartilage-related diseases such as
      osteoarthritis.

PMID- 29057472
TI  - Pharmacokinetics of furosemide administered 4 and 24 hours prior to high-speed
      exercise in horses.
AB  - Furosemide is a diuretic agent used commonly in racehorses to attenuate the
      bleeding associated with exercise-induced pulmonary hemorrhage (EIPH). The
      current study describes serum and urine concentrations and the pharmacokinetics
      of furosemide following administration at 4 and 24 hrs prior to maximal exercise.
      Eight exercised adult Thoroughbred horses received a single IV administration of
      250 mg of furosemide at 4 and 24 hrs prior to maximal exercise on a high-speed
      treadmill. Blood and urine samples were collected at time 0 and at various times
      for up to 72 hrs and furosemide concentrations determined using liquid
      chromatography-tandem mass spectrometry. Serum furosemide concentrations remained
      above the LOQ (0.05 ng/ml) for 36 hrs in 3/8 and 1/8 horses in the 4- and 24-hrs
      groups, respectively. Serum concentration data were best fit by a two-compartment
      model. There was not a significant difference in the volume of distribution at
      steady-state (0.594 +/- 0.178 [4 hrs] and 0.648 +/- 0.147 [24 hrs] L/kg) or
      systemic clearance (0.541 +/- 0.094 [4 hrs] and 0.617 +/- 0.114 [24 hrs]
      L/hrs/kg) between horses that were exercised at 4- and 24 hrs postdrug
      administration. The mean +/- SD elimination half-life was 3.12 +/- 0.387 and 3.23
      +/- 0.407 hrs following administration at 4 and 24 hrs prior to exercise,
      respectively.

PMID- 29057473
TI  - Postoperative pharmacokinetics of meloxicam in horses after surgery for colic
      syndrome.
AB  - NSAIDs are often used in horses with colic syndrome during the postoperative
      period, due to their ability to contrast endotoxemia and to promote an analgesic
      and anti-inflammatory effect. As the pharmacokinetics of a drug are often
      modified in unhealthy animals compared to healthy subjects, the aim of this study
      was to evaluate the pharmacokinetic profile of meloxicam after i.v.
      administration in horses undergoing laparotomy for colic syndrome. Eight horses
      received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples
      were taken at scheduled time points during the following 24 hr. The serum
      concentration of the drug was determined by HPLC. Terminal half-life (6.88 +/-
      2.96 hr), volume of distribution at steady-state (186.53 +/- 61.20 ml/Kg) and
      clearance (27.91 +/- 5.72 ml kg-1  hr-1 ) were similar to those reported in
      literature for healthy horses. This result suggests that no adjustment of the
      approved dose should be necessary when meloxicam is used to treat horses in the
      immediate postoperative period after surgery for colic syndrome.

PMID- 29057474
TI  - Intraspecific variation in embolism resistance and stem anatomy across four
      sunflower (Helianthus annuus L.) accessions.
AB  - Drought-induced xylem embolism is a key process closely related to plant
      mortality during extreme drought events. However, this process has been poorly
      investigated in crop species to date, despite the observed decline of crop
      productivity under extreme drought conditions. Interspecific variation in
      hydraulic traits has frequently been reported, but less is known about
      intraspecific variation in crops. We assessed the intraspecific variability of
      embolism resistance in four sunflower (Helianthus annuus L.) accessions grown in
      well-watered conditions. Vulnerability to embolism was determined by the in situ
      flow-centrifuge method (cavitron), and possible trade-offs between xylem safety,
      xylem efficiency and growth were assessed. The relationship between stem anatomy
      and hydraulic traits was also investigated. Mean P50 was -3 MPa, but significant
      variation was observed between accessions, with values ranging between -2.67 and 
      3.22 MPa. Embolism resistance was negatively related to growth and positively
      related to xylem-specific hydraulic conductivity. There is, therefore, a trade
      off between hydraulic safety and growth but not between hydraulic safety and
      efficiency. Finally, we found that a few anatomical traits, such as vessel
      density and the area of the vessel lumen relative to that of the secondary xylem,
      were related to embolism resistance, whereas stem tissue lignification was not.
      Further investigations are now required to investigate the link between the
      observed variability of embolism resistance and yield, to facilitate the
      identification of breeding strategies to improve yields in an increasingly arid
      world.

PMID- 29057475
TI  - Erding Formula in hyperuricaemia treatment: unfolding traditional Chinese herbal
      compatibility using modern pharmaceutical approaches.
AB  - OBJECTIVES: Traditional Chinese herbal formulas are difficult to be understood
      because of complex compositions and specific therapeutic principles. To better
      understand herbal compatibility in Traditional Chinese medicine (TCM), this study
      was conducted to investigate the effects of a Chinese pharmacopoeia-listed
      formula, Erding Formula (EF) and its constituent herbs for a new indication,
      hyperuricaemia. METHODS: A hypoxanthine and potassium oxonate-induced
      hyperuricemic mouse model, a xylene-induced inflammatory mouse model and an
      acetic acid-induced pain model were used to test the effects of EF and its
      constituent herbs. In addition, we investigated whether EF and/or its relevant
      herbs had an impact on the expression of URAT1 and OAT3 mRNA. KEY FINDINGS: The
      results showed EF and individual herbs had pharmacological effects on selected
      targets. Only Viola yedoensis Makino (Viola) lowered uric acid levels, while all
      four herbs had anti-inflammatory and analgesic effects. The EF may lower the uric
      acid level through inhibiting the expression of URAT1 mRNA and enhancing the
      expression of OAT3 mRNA. CONCLUSIONS: These findings provide pharmacological
      insights into the effects of EF and individual herbs on UA excretion. This study
      suggests that Viola is the main herb in EF. This study facilitates better
      understanding of TCM principles and theories using modern pharmaceutical
      approaches.

PMID- 29057476
TI  - Therapeutic potency of pharmacological adenosine receptor agonist/antagonist in
      angiogenesis, current status and perspectives.
AB  - OBJECTIVES: Adenosine concentration significantly increases in tumour
      microenvironment contributing to tumorigenic processes including cell
      proliferation, survival, invasion and of special interest in this review
      angiogenesis. KEY FINDINGS: This review summarizes the role of pharmacological
      adenosine receptor agonist and antagonist in regulating angiogenesis for a better
      understanding and hence a better management of angiogenesis-associated disorders.
      SUMMARY: Depending upon the pharmacological characteristics of adenosine receptor
      subtypes, adenosine elicits anti- or pro-angiogenic responses in stimulated
      cells. Inhibition of the stimulatory effect of adenosine signalling on
      angiogenesis using specific pharmacological adenosine receptor agonist, and
      antagonist is a potentially novel strategy to suppress angiogenesis in tumours.

PMID- 29057477
TI  - The MIP-1alpha autocrine loop contributes to decreased sensitivity to anticancer
      drugs.
AB  - Several autocrine soluble factors, including macrophage inflammatory protein
      1alpha (MIP-1alpha), tumor necrosis factor-alpha, and hepatocyte growth factor,
      promote cell survival and growth in multiple myeloma (MM) cells. We hypothesized
      that inhibition of the MIP-1alpha autocrine loop may enhance the cytotoxic effect
      of anticancer drugs in MM cell lines. In the present study, an MIP-1alpha
      neutralizing antibody suppressed cell proliferation and enhanced the cytotoxic
      effect of melphalan or bortezomib on MM cells. In addition, melphalan resistance
      cells (RPMI8226/L-PAM and HS-sultan/L-PAM cells) secreted MIP-1alpha and
      neutralizing antibody of MIP-1alpha partially overcame melphalan resistance.
      Moreover, combination treatment with MIP-1alpha neutralizing antibody and
      melphalan or bortezomib inhibited extracellular signal regulated kinase 1/2
      (ERK1/2), Akt, and mammalian target of rapamycin (mTOR) activation, Bcl-2, Bcl
      xL, and Survivin expression, and upregulated the expression of Bim and cleaved
      Poly (ADP-ribose) polymerase (PARP). Treatment of IM9 cells with MIP-1alpha siRNA
      suppressed the activation of ERK1/2, Akt, and mTOR, and enhanced the cytotoxic
      effect of melphalan and bortezomib. These results indicate that MIP-1alpha
      neutralizing antibodies or MIP-1alpha siRNA enhance the cytotoxic effect of
      melphalan and bortezomib by suppressing the chemokine receptor/ERK and chemokine
      receptor/Akt/mTOR pathways. The inhibition of MIP-1alpha may thus provide a new
      therapeutic approach to control tumor progression and bone destruction in
      patients with MM.

PMID- 29057478
TI  - Decoy receptor 3 promotes cell adhesion and enhances endometriosis development.
AB  - Endometriosis is a multifactorial inflammatory disease with persistent activation
      of the nuclear factor-kappaB (NF-kappaB) signalling pathway. Aberrant adhesion of
      endometrium is the essential step in the progression of endometriosis, but the
      molecular mechanism of ectopic growth of endometrium is still unclear. Decoy
      receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen,
      is able to activate focal adhesion kinase to promote cell adhesion. We found that
      DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt
      NF-kappaB signalling pathway, and its expression level correlates positively with
      that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and
      homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model,
      DcR3 expression level was the most significant parameter associated with
      endometriosis severity. Knockdown of DcR3 not only downregulated the expression
      of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo
      investigation further showed that DcR3 promoted the growth and spread of
      endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA
      inhibited ectopic adhesion of endometrium and abrogated endometriosis
      progression. These observations are in support of DcR3 playing a critical role in
      the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a
      promising approach for the treatment of endometriosis. Copyright (c) 2017
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29057479
TI  - Ketoprofen pharmacokinetics of R- and S-isomers in juvenile loggerhead sea
      turtles (Caretta caretta) after single intravenous and single- and multidose
      intramuscular administration.
AB  - Ketoprofen is a nonsteroidal anti-inflammatory and analgesic agent that
      nonselectively inhibits cyclooxygenase, with both COX-1 and COX-2 inhibition.
      Recent studies on COX receptor expression in reptiles suggest that nonselective
      COX inhibitors may be more appropriate than more selective inhibitors in some
      reptiles, but few pharmacokinetic studies are available. The goal of this study
      was to determine single- and multidose (three consecutive days) pharmacokinetics
      of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg
      in healthy juvenile loggerhead turtles (Caretta caretta). The S-isomer is the
      predominant isomer in loggerhead sea turtles, similar to most mammals, despite
      administration of a 50:50 racemic mixture. Multidose ketoprofen administration
      demonstrated no bioaccumulation; therefore, once-daily dosing will not require
      dose adjustment over time. S-isomer pharmacokinetic parameters determined in this
      study were Cmax of 10.1 MUg/ml by IM injection, C0 of 13.4 MUg/ml by IV
      injection, AUC of 44.7 or 69.4 MUg*hr/ml by IM or IV injection, respectively, and
      T1/2 of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen
      plasma concentrations were maintained for at least 12 hr above concentrations
      determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV
      every 24 hr is likely appropriate for loggerhead turtles.

PMID- 29057480
TI  - Cannabinoids concentration variability in cannabis olive oil galenic
      preparations.
AB  - OBJECTIVES: Knowledge of the exact concentration of active compounds in galenic
      preparations is crucial to be able to ensure their quality and to properly
      administer the prescribed dose. Currently, the need for titration of extracts is
      still debated. Considering this, together with the absence of a standard
      preparation method, the aim of this study was to evaluate cannabinoids
      concentrations variability in galenic olive oil extracts, to evaluate the
      interlot and interlaboratory variability in the extraction yield and in the
      preparation composition. METHODS: Two hundred and one extracts (123 (61.2%) from
      Bedrocan(r) , 54 (26.9%) from Bediol(r) , 11 (5.5%) from Bedrolite(r) , and 13
      (6.5%) from mixed preparations) were analysed by liquid chromatography coupled
      with tandem mass spectrometry, quantifying cannabinoids (THC, CBD, THCA, CBDA and
      CBN) concentrations. KEY FINDINGS: The RSD% of THC and CBD concentrations
      resulted higher than 50%. Specifically for Bedrocan(r) , Bediol(r) , Bedrolite(r)
      (5 g/50 ml), these were THC 82%, THC 53% and CBD 91%, THC 58% and CBD 59%,
      respectively. The median extraction yields were greater than 75% for all
      preparations. CONCLUSIONS: Our results highlighted a wide variability in THC and
      CBD concentrations that justify the need for titration and opens further
      questions about other pharmaceutical preparations without regulatory indication
      for this procedure.

PMID- 29057481
TI  - The Shc protein RAI promotes an adaptive cell survival program in hypoxic
      neuroblastoma cells.
AB  - Neuroblastoma (NB) is a highly malignant pediatric solid tumor where a hypoxic
      signature correlates with unfavorable patient outcome. The hypoxia-inducible
      factor (HIF)-1alpha plays an important role in NB progression, contributing to
      cell proliferation and invasiveness. RAI belongs to the Shc family proteins, it
      is mainly neuron specific and protects against cerebral ischemia. RAI is also
      expressed in several NB cell lines, where it promotes cell survival. In this
      work, hypoxia differently affected cell survival and pro-apoptotic program in two
      NB cell lines, either expressing RAI (SKNBE) or not (SKNMC). RAI expression
      appeared to promote NB cell survival and to reduce some pro-apoptotic markers
      under hypoxia. Accordingly, the RAI silencing in SKNBE cells resulted in a
      reduction of cell survival and HIF-1alpha expression. Furthermore, using SKNMC
      cells stably expressing RAI, we defined a role of RAI in NB cell responses to
      hypoxia. Of interest, in hypoxic SKNMC cells expressing RAI HIF-1alpha protein
      levels were higher than in control cells. This was associated with a) an
      increased cell survival; b) an increased expression of anti-apoptotic markers; c)
      a pro-autophagic and not pro-apoptotic phenotype; and d) an increased metabolic
      activity. We may conclude that RAI plays an important role in hypoxic signaling
      in NB cells and the interplay between RAI and HIF-1alpha may be relevant in the
      protection of NB cells against hypoxia. Our results may contribute to a further
      understanding the physiology of NB cells and the molecular mechanisms involved in
      their survival, with important implications in NB progression.

PMID- 29057482
TI  - Evaluation of the safety of daily administration of capromorelin in cats.
AB  - Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite
      stimulation in dogs. The objective of this study was to evaluate the safety of
      daily oral administration of capromorelin to cats over a range of doses and for
      an extended period. Two randomized, controlled studies were conducted: in Study
      1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30
      or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at
      6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated
      using clinical observations and clinical pathology test results for both studies,
      with the addition of postmortem examination in Study 1 and measurements of growth
      hormone and insulin-like growth factor 1 in Study 2. Abnormal clinical
      observations were limited to emesis, hypersalivation, lethargy/depression, head
      shaking and lip smacking, which occurred more frequently in the capromorelin
      treated groups than in the placebo group. There were no clinically relevant
      differences in clinical pathology test results between the capromorelin and
      placebo groups in either study.

PMID- 29057483
TI  - The promise of marine molecules as cosmetic active ingredients.
AB  - The marine environment represents an underexploited resource for the discovery of
      novel products, despite its high level of biological and chemical diversity. With
      increasing awareness of the harmful effects of chronic ultraviolet exposure, and
      a universal desire to improve cosmetic appearance, the market for new cosmetic
      ingredients is growing, and current trends have generated a greater demand for
      products sourced from the environment. A growing number of novel molecules from
      marine flora and fauna exhibit potent and effective dermatological activities.
      Secondary metabolites isolated from macroalgae, including carotenoids and
      polyphenols, have demonstrated antioxidant, anti-ageing and anti-inflammatory
      activities. In addition, marine extremophilic bacteria have recently been shown
      to produce bioactive exopolymeric molecules, some of which have been
      commercialized. Available data on their activities show significant antioxidant,
      moisturizing and anti-ageing activities, but a more focussed investigation into
      their mechanisms and applications is required. This review surveys the reported
      biological activities of an emerging and growing portfolio of marine molecules
      that show promise in the treatment of cosmetic skin problems including
      ultraviolet damage, ageing and cutaneous dryness.

PMID- 29057484
TI  - Biochemical and functional characterization of AcUFGT3a, a galactosyltransferase
      involved in anthocyanin biosynthesis in the red-fleshed kiwifruit (Actinidia
      chinensis).
AB  - Much of the diversity of anthocyanin pigmentation in plant tissues is due to the
      action of glycosyltransferases, which attach sugar moieties to the anthocyanin
      aglycone. This step can increase both their solubility and stability. We
      investigated the pigmentation of the outer and inner pericarps of developing
      fruits of the red-fleshed kiwifruit Actinidia chinensis cv. 'Hongyang'. The
      results show that the red color of the inner pericarp is due to anthocyanin.
      Based on expression analyses of structural genes, AcUFGT was shown to be the key
      gene involved in the anthocyanin biosynthetic pathway. Expression of AcUFGT in
      developing fruit paralleled changes in anthocyanin concentration. Thirteen
      putative UFGT genes, including different transcripts, were identified in the
      genome of 'Hongyang'. Among these, only the expression of AcUFGT3a was found to
      be highly consistent with anthocyanin accumulation. Fruit infiltrated with virus
      induced gene silencing showed delayed red colorations, lower anthocyanin contents
      and lower expressions of AcUFGT3a. At the same time, transient overexpression of
      AcUFGT3a in both Actinidia arguta and green apple fruit resulted in higher
      anthocyanin contents and deeper red coloration. In vitro biochemical assays
      revealed that recombinant AcUFGT3a recognized only anthocyanidins as substrate
      but not flavonols. Also, UDP-galactose was used preferentially as the sugar
      donor. These results indicate AcUFGT3a is the key enzyme regulating anthocyanin
      accumulation in red-fleshed kiwifruit.

PMID- 29057485
TI  - Roots-eye view: Using microdialysis and microCT to non-destructively map root
      nutrient depletion and accumulation zones.
AB  - Improvement in fertilizer use efficiency is a key aspect for achieving
      sustainable agriculture in order to minimize costs, greenhouse gas emissions, and
      pollution from nutrient run-off. To optimize root architecture for nutrient
      uptake and efficiency, we need to understand what the roots encounter in their
      environment. Traditional methods of nutrient sampling, such as salt extractions
      can only be done at the end of an experiment, are impractical for sampling
      locations precisely and give total nutrient values that can overestimate the
      nutrients available to the roots. In contrast, microdialysis provides a non
      invasive, continuous method for sampling available nutrients in the soil. Here,
      for the first time, we have used microCT imaging to position microdialysis probes
      at known distances from the roots and then measured the available nitrate and
      ammonium. We found that nitrate accumulated close to roots whereas ammonium was
      depleted demonstrating that this combination of complementary techniques provides
      a unique ability to measure root-available nutrients non-destructively and in
      almost real time.

PMID- 29057486
TI  - Prediction of a nail polish colour applied on a nail.
AB  - OBJECTIVE: The colour of a nail polish varies according to the nail on which it
      is applied. The objective of this study was to predict the colour of the nail
      polish on a given nail and to study how the colour varies depending on the nail
      polish thickness. METHODS: Six nail polishes were applied in one, two and three
      layers on the nails of one subject, thus forming eighteen samples. The spectral
      reflectances of the eighteen nail polishes applied on the nails with different
      thicknesses were obtained by spectrophotometry. The spectral reflectances of the
      nails without polish were also measured using the same technique. The thicknesses
      of nail polishes were measured by high-definition optical coherence tomography
      (HD-OCT). Then, to determine the physical parameters of the nail polish itself,
      we applied the six nail polishes on an opacity drawdown chart and we measured the
      spectral reflectance and the thickness of each patch using spectrophotometry and
      HD-OCT, respectively. The Kubelka-Munk theory was used to get the predicted
      spectral reflectance of the nail polish applied on the nail according to the
      polish thickness by knowing the parameter of the polish itself and the spectral
      reflectance of the nail. The predicted spectral reflectances were finally
      compared with those measured directly on the nails. RESULTS: The predicted
      spectral reflectances were rather close to measured ones. Consequently, knowing
      the colour of the nail without polish and the optical parameters of the nail
      polish itself, we can estimate the colour of the nail polish applied on the nail
      depending on its thickness. CONCLUSION: Our study showed that the Kubelka-Munk
      theory can be used to predict the nail polish colour. The ability to predict the
      real colour of a nail polish applied on a nail could help a nail polish
      manufacturer to improve his polish formulae in order to obtain a precise colour.

PMID- 29057487
TI  - A systematic review of nonpharmacological prenatal interventions for pregnancy
      specific anxiety and fear of childbirth.
AB  - BACKGROUND: Despite a sharp increase in the number of publications that report on
      treatment options for pregnancy-specific anxiety and fear of childbirth
      (PSA/FoB), no systematic review of nonpharmacological prenatal interventions for
      PSA/FoB has been published. Our team addressed this gap, as an important first
      step in developing guidelines and recommendations for the treatment of women with
      PSA/FoB. METHODS: Two databases (PubMed and Mendeley) were searched, using a
      combination of 42 search terms. After removing duplicates, two authors
      independently assessed 208 abstracts. Sixteen studies met eligibility criteria,
      ie, the article reported on an intervention, educational component, or treatment
      regime for PSA/FoB during pregnancy, and included a control group. Independent
      quality assessments resulted in the retention of seven studies. RESULTS: Six of
      seven included studies were randomized controlled trials (RCTs) and one a quasi
      experimental study. Five studies received moderate quality ratings and two strong
      ratings. Five of seven studies reported significant changes in PSA/FoB, as a
      result of the intervention. Short individual psychotherapeutic interventions (1.5
      5 hours) delivered by midwives or obstetricians were effective for women with
      elevated childbirth fear. Interventions that were effective for pregnant women
      with a range of different fear/anxiety levels were childbirth education at the
      hospital (2 hours), prenatal Hatha yoga (8 weeks), and an 8-week prenatal
      education course (16 hours). CONCLUSIONS: Findings from this review can inform
      the development of treatment approaches to support pregnant women with PSA/FoB.

PMID- 29057488
TI  - Meta-analysis of pesticide sorption in subsoil.
AB  - Models used to assess leaching risks generally use organic carbon partition
      coefficient (kOC ) values derived from batch experiments on topsoil samples to
      estimate pesticide sorption in subsoils of much smaller organic carbon contents.
      This can introduce significant errors in leaching risk calculations, because
      inorganic sorbents can play an important role for sorption in subsoil. The
      objectives of the present study were therefore to summarize the available
      literature data on pesticide sorption in subsoils and to test whether a simple
      alternative model could improve on the standard kOC approach used in risk
      assessment models for pesticide leaching. This model describes the sorption
      constant as a power law function of the organic carbon content. A database with
      the results of batch sorption experiments was collated from published studies
      that emphasized measurements in subsoils. This database contains 1029 data
      entries from 36 published studies with data for 29 active substances (11 nonionic
      compounds, 10 weak acids, 6 weak bases, one cation, and one zwitterion). The
      results show that whereas the constant kOC model proved to be an adequate model
      for 17 of the 63 individual datasets, the power law model gave acceptable fits (p
      < 0.05) for 60 of these cases. The exponent in the power law model varied over a
      wide range, from slightly negative to near unity. It also differed significantly
      (p = 0.015) for ionized and nonionized compounds, with median values of 0.25 and
      0.55, respectively. It is concluded that the power law model could be used to
      parameterize subsoil sorption in regulatory leaching models, because it has
      widespread applicability and is simple enough for this purpose. Suitable ways of
      incorporating this approach in risk assessment procedures are discussed. Environ
      Toxicol Chem 2018;37:755-761. (c) 2017 SETAC.

PMID- 29057489
TI  - Endocan is markedly overexpressed in severe erectile dysfunction.
AB  - This study aimed to measure the serum endocan level of patients with erectile
      dysfunction (ED) and to investigate the possible association between this and
      vasculogenic severe ED. We performed a prospective analysis of 86 consecutive
      patients affected by ED. Patients were divided into severe ED (IIEF-5 score < 7)
      and mild or moderate ED (IIEF-5 score > 7). A strong negative correlation was
      found between serum endocan levels and peak systolic velocity (p < .001 and r = 
      .665) in men with severe ED. Univariate logistic regression analysis demonstrated
      that tobacco consumption (p < .05), serum total 25-hydroxyvitamin D (p < .01),
      serum endocan levels (p < .01), peak systolic velocity (p < .01), hypertension (p
      < .001), dyslipidaemia (p < .001), metabolic syndrome (p = .026) and a history of
      a cardiovascular event (p < .001) significantly increase the risk of severe ED.
      In the multivariate logistic regression model, we also found that age,
      hypertension, metabolic syndrome, cardiovascular events and higher serum endocan
      levels were independently associated with severe ED. Circulating endocan may be
      used in daily practice as a new marker that correlates with cardiovascular risks
      and the severity of ED disease.

PMID- 29057490
TI  - When Cars Hit Trucks and Girls Hug Boys: The Effect of Animacy on Word Order in
      Gestural Language Creation.
AB  - A well-known typological observation is the dominance of subject-initial word
      orders, SOV and SVO, across the world's languages. Recent findings from gestural
      language creation paradigms offer possible explanations for the prevalence of
      SOV. When asked to gesture transitive events with an animate agent and inanimate
      patient, gesturers tend to produce SOV order, regardless of their native language
      biases. Interestingly, when the patient is animate, gesturers shift away from SOV
      to use of other orders, like SVO and OSV. Two competing hypotheses have been
      proposed for this switch: the noisy channel account (Gibson et al., 2013) and the
      role conflict account (Hall, Mayberry, & Ferreira, 2013). We set out to
      distinguish between these two hypotheses, disentangling event reversibility and
      patient animacy, by looking at gestural sequences for events with two inanimate
      participants (inanimate-inanimate, reversible). We replicated the previous
      findings of a preference for SOV order when describing animate-inanimate,
      irreversible events as well as a decrease in the use of SOV when presented with
      animate-animate, reversible events. Accompanying the drop in SOV, in a novel
      condition we observed an increase in the use of SVO and OSV orders when
      describing events involving two animate entities. In sum, we find that the
      observed avoidance of SOV order in gestural language creation paradigms when the
      event includes an animate agent and patient is driven by the animacy of the
      participants rather than the reversibility of the event. We suggest that findings
      from gestural creation paradigms are not automatically linkable to spoken
      language typology.

PMID- 29057491
TI  - Insight into curcumin nanomicelle-induced derangements in male reproduction
      potential: An experimental study.
AB  - This study was conducted to investigate the possible effects of nanomicelle
      curcumin (NMC) on spermatogenesis, sperm parameters and in vitro fertilisation
      potential. For this purpose, 24 mature male Wistar rats were divided into control
      and test groups. The animals in test groups received 7.5, 15 and 30 mg kg b.w-1
      of NMC (NO = 6 rats in each group). Following 48 days, the DNA integrity of
      testicular tissues, tubular differentiation (TDI) and spermiogenesis (SPI)
      indices, sperm parameters and DNA integrity were analysed. Finally, the in vitro
      fertilisation potential was investigated via evaluating pre-implantation embryo
      generation. The NMC diminished the TDI and SPI ratios. The animals in NMC
      received groups exhibited a remarkable (p < .05) reduction in percentage of alive
      and motile spermatozoa. Moreover, the NMC enhanced the percentage of spermatozoa
      with decondensed chromatin and elevated the sperm DNA damage ratio. The testicles
      of NMC-received groups exhibited severe DNA fragmentation. The percentages of
      zygote, 2-cell, blastocysts and hatched embryos generation were decreased in NMC
      received groups compared to control animals. In conclusion, the NMC adversely
      affects the spermatogenesis and spermiogenesis processes, which in turn results
      in reducing the sperm quality. Ultimately, decreased sperm quality results in
      lower pre-implantation embryo development.

PMID- 29057492
TI  - QTc prolongation during ciprofloxacin and fluconazole combination therapy:
      prevalence and associated risk factors.
AB  - AIM(S): Ciprofloxacin and fluconazole combination therapy is frequently used as
      prophylaxis for, and treatment of, infections in patients with haematological
      malignancies. However, both drugs are known to prolong the heart rate-corrected
      QT (QTc) interval, which is a serious risk factor for torsade de pointes (TdP).
      Therefore, the aim of the current study was to assess the prevalence of QTc
      prolongation during ciprofloxacin and fluconazole use. The secondary objective
      was to determine associated risk factors of QTc prolongation in these patients.
      METHODS: A prospective observational study was performed in patients admitted to
      the Erasmus University Medical Centre and treated with ciprofloxacin and
      fluconazole. A 12-lead electrocardiogram (ECG) was recorded at the estimated time
      to peak concentration (Tmax ) for the last added drug. The main outcome was the
      proportion of patients with QTc prolongation during treatment. Data on the
      following potential risk factors were collected: patient characteristics, serum
      electrolyte levels, dosage of ciprofloxacin and fluconazole, renal and liver
      function and concomitant use of other QTc-prolonging drugs and cytochrome P450
      3A4 inhibitors. RESULTS: A total of 170 patients were included, of whom 149
      (87.6%) were treated for haematological malignancies. The prevalence of QTc
      prolongation was 4.7%. No risk factors were found to be associated with QTc
      prolongation. The QTc interval increased by 10.7 ms [95% confidence interval (CI)
      7.2, 14.1 ms] during ciprofloxacin and fluconazole combination therapy.
      CONCLUSION: The prevalence of QTc prolongation in patients using ciprofloxacin
      and fluconazole is low compared with the prevalence in the general population,
      which varies from 5% to 11%. In addition, no risk factors were found. Given the
      low prevalence, routine ECG monitoring in patients on this therapy should be
      reconsidered.

PMID- 29057493
TI  - Determination of seminal oxidation-reduction potential (ORP) as an easy and cost
      effective clinical marker of male infertility.
AB  - Oxidative stress (OS) is an important contributing factor to male infertility.
      While previous methods to measure seminal OS are time-consuming and limited to
      the use of freshly produced semen, oxidation reduction potential (ORP) is easier
      and quicker to perform and can also be used in frozen semen. Therefore, this
      study evaluated the clinical utility of ORP as a potential marker of male
      infertility. ORP was measured in semen samples from 293 patients and 15 fertile
      controls and categorised according to WHO criteria as normozoospermic,
      oligozoospermic, asthenozoospermic, teratozoospermic and
      oligoasthenoteratozoospermic. Receiver operating characteristic (ROC) curves were
      generated to differentiate these categories. Semen parameters were significantly
      different when subjects were grouped as control and patients or between the
      patient and normozoospermic group for concentration and morphology. ORP levels
      were significantly different between the control and normozoospermic group. When
      subjects were grouped based on concentration, motility, morphology or a
      combination of these, the area under the ROC curve, sensitivity, specificity,
      positive predictive value and cut-off values were significantly different. These
      differences were significant when combined with ORP and grouped with any two
      sperm abnormalities. In conclusion, ORP is a quick, easy, cost-effective and
      reliable marker of semen quality as well as oxidative stress for use in a
      clinical setting.

PMID- 29057494
TI  - A decrease in serum 1,5-anhydroglucitol levels is associated with the presence of
      a first-degree family history of diabetes in a Chinese population with normal
      glucose tolerance.
AB  - AIM: This study aimed to investigate alterations in HbA1c , glycated albumin (GA)
      and 1,5-anhydroglucitol (1,5-AG) in Chinese first-degree relatives of individuals
      with diabetes (FDR) in pursuit of an index for early screening of glucose
      metabolism disturbance. METHODS: A total of 467 participants (age range: 20-78
      years) with normal weight and normal glucose tolerance, as determined by a 75-g
      oral glucose tolerance test, were enrolled. HbA1c was measured using high
      performance liquid chromatography. Serum GA and 1,5-AG levels were determined by
      enzymatic methods. Serum insulin levels were measured using an
      electrochemiluminescence immunoassay. RESULTS: The study population included 208
      FDR and 259 non-FDR. Serum 1,5-AG levels were lower in FDR than that in non-FDR
      (20.4 +/- 7.5 vs 23.8 +/- 8.3 MUg/ml, P < 0.001), but HbA1c and GA levels did not
      differ between them (P = 0.835 and 0.469, respectively). Logistic regression
      analysis revealed an independent relationship between a first-degree family
      history of diabetes and reduced serum 1,5-AG levels (odds ratio = 0.944, P <
      0.001). Multiple regression analysis showed that a first-degree family history of
      diabetes (beta = -3.041, P < 0.001) and insulinogenic index (beta = 0.081, P =
      0.001) were independently associated with serum 1,5-AG levels. CONCLUSION: In a
      Chinese population with normal glucose tolerance, serum 1,5-AG levels were lower
      among FDR, and serum 1,5-AG levels were independently associated with FDR status.
      For FDR, serum 1,5-AG levels were more sensitive than HbA1c or GA levels to early
      phase abnormality in glucose metabolism.

PMID- 29057495
TI  - Impact of varicocelectomy on the proteome profile of testicular tissues of rats
      with varicocele.
AB  - Varicocele (VC) is a common cause of male infertility, but the molecular
      mechanisms involved in its pathogenesis are unknown. We investigated the impact
      of varicocelectomy (VCT) on proteome profiles in testicular tissues of rats with
      VC, and analysed associated target genes and signalling pathways. Sixty male rats
      with VC were divided into two groups: control (n = 30), and VCT (n = 30). Tissues
      were collected 4 weeks after sham or VCT surgery. Matrix-assisted laser
      desorption/ionisation time-of-flight/time-of-flight mass spectrometry (MALDI
      TOF/TOF MS) was used to analyse the comparative proteome profiles. Kyoto
      Encyclopaedia of Genes and Genomes (KEGG) Orthology-Based Annotation System was
      used for bioinformatic analysis. Fifteen proteins were differentially expressed
      between control and VCT groups. These differentially expressed proteins are
      associated with several specific cellular processes associated with the
      pathogenesis of testicular growth arrest associated with VC. Furthermore, the
      evaluation by transmission electron micrograph showed that VCT could decrease
      apoptosis of spermatogenic cells in rats. Understanding such molecular pathways
      might provide physicians with a better insight into VC and with potential targets
      for treatment.

PMID- 29057496
TI  - Media coverage of the 'UK flooding crisis': a social panorama.
AB  - A disaster referred to by the press as the 'UK flooding crisis' occurred between
      December 2015 and January 2016. This study employed three different levels of
      analysis to identify a multidimensional perspective adopted in the disaster
      reporting of the British Broadcasting Corporation (BBC). These levels revealed
      details about the social actors and their interactions. The set of news exposed
      diverse viewpoints on the crisis, from loss and damage to distinct affected
      subgroups to the various social engagement actions of aid and the multiplicity of
      technical response measures. The conclusions highlight considerable social
      amplitude in the BBC's coverage; however, owing to the reductionist approach of
      this media communicator, the field of action involving different social actors
      was not very clear in the content of the news, particularly with regard to
      cohesion, conflict/obstruction, and concernthe concept of crisis in its essence.
      In addition, the paper suggests new questions for future reports.

PMID- 29057497
TI  - Molecular modeling studies to explore the binding affinity of virtually screened
      inhibitor toward different aminoglycoside kinases from diverse MDR strains.
AB  - Antibiotic resistance to aminoglycoside group of antibiotics mainly occurs by
      aminoglycoside kinases (AKs). Thus, targeting AKs from different multidrug
      resistant (MDR) strains could result into inhibition of AK enzymes and ultimately
      the resistance. Therefore, the present study aims to target one of these AKs that
      is APH(3')-Ia from Acinetobacter baumannii through structure based virtual
      screening (SBVS) and test the binding affinity of the most stable virtually
      screened inhibitor with AKs from Mycobacterium tuberculosis, Acinetobacter
      baumannii, Enterococcus gallinarum, and Escherichia coli. SBVS investigated
      ZINC71575479 as a most stable inhibitor with -8.92 kcal/mol of binding energy and
      0.66 uM of inhibition constant. Molecular docking results revealed that the
      ZINC71575479 can efficiently bind to nucleotide triphosphate (NTP) binding site
      of different AKs which is a known drug target site. Sequence analysis study of
      different AKs showed no significant similarity for active site residues; however
      structure superimposition study showed conserved NTP-binding domain. Molecular
      dynamics (MD) simulations showed stable behavior of all docked complexes with
      notable conformational stability of salt bridges at NTP-binding site of different
      AKs. Binding energy calculations revealed the interactions between key residues
      from NTP- binding domain of different AKs with ZINC71575479. In order to validate
      the MD simulations and binding energy results, crystal structure complexed with
      tyrphostin AG1478 a known inhibitor of AKs was kept as control. Thus, this work
      demonstrates the binding efficiency of ZINC71575479 toward different AKs for
      circumventing aminoglycoside resistance and opens avenues for the development of
      new antibiotics that can target diverse MDR strains with aminoglycoside
      resistance.

PMID- 29057499
TI  - GCNF regulates OCT4 expression through its interactions with nuclear receptor
      binding elements in NCCIT cells.
AB  - We demonstrate that OCT4 expression is regulated by germ cell nuclear factor
      (GCNF) via its interactions with three nuclear receptor (NR) binding sites within
      OCT4 promoter conserved regions (CRs) in human embryonic carcinoma (EC) NCCIT
      cells. OCT4 expression is gradually reduced during the retinoic acid-induced
      differentiation, while GCNF temporarily increased after 2 days and then
      significantly decreased. In addition, OCT4 expression is significantly reduced by
      overexpression of exogenous GCNF, but increased by GCNF shRNA-mediated knockdown.
      The transcriptional activity of OCT4 is significantly inhibited by dose-dependent
      overexpression of GCNF. While mutants at each of the NR binding sites retain the
      repressive effects of GCNF on OCT4 promoter activity, the repressive effect was
      completely eliminated in the reporter construct with all binding sites mutated
      even in the presence of GCNF. Furthermore, the transcriptional activity of native
      minimal promoter (CR1-Luc) containing the first NR binding site was significantly
      reduced by GCNF overexpression, while the mutant retained basal activity to some
      extent. Next, an exogenous minimal ti promoter-inserted CR2 reporter construct
      containing the second and third NR binding sites (CR2-ti-Luc) was co-transfected
      with GCNF expression vector. The transcriptional activity of CR2-ti-Luc was
      significantly decreased by GCNF overexpression, while mutation of both binding
      sites retained the transcriptional activity of the reporter construct. Binding
      assays confirmed the direct interaction of GCNF with all three NR binding sites
      cooperatively. Taken together, GCNF acts as a transcriptional repressor in the
      regulation of OCT4 gene expression through cooperative interaction with three NR
      binding elements in pluripotent NCCIT cells.

PMID- 29057498
TI  - Acetylation and methylation of sperm histone 3 lysine 27 (H3K27ac and H3K27me3)
      are associated with bull fertility.
AB  - Epigenetic modifications in histones are crucial for proper sperm physiology, egg
      activation and reproductive development of males. The objectives of this study
      were to determine the conservation and interactomes of histone three (H3) and
      ascertain the expression dynamics of acetylated and methylated H3 lysine 27
      (H3K27ac and H3K27me3) in spermatozoa from Holstein bulls with different
      fertility. Methods in immunocytochemistry and flow cytometry were used to
      evaluate the expression dynamics of H3K27ac and H3K27me3 in spermatozoa from 10
      bulls with different in vivo fertility. Computational biology methods including
      Clustal Omega and Cytoscape were performed to determine the evolutionary
      conservation and interactome of H3. The post-translational modifications (PTM) of
      H3 (H3K27ac and H3K27me3) had different spatiotemporal dynamics in the sperm
      head. Intensities of methylation were higher than those of acetylation and
      inversely correlated between the two fertility groups (p = .0032). The
      interacting proteins of H3 are involved in critical subcellular processes such as
      regulation of methylation, nucleosome assembly, regulation of DNA replication and
      chromatin assembly. These results are significant because they help advance
      fundamental science and biotechnology of mammalian reproduction.

PMID- 29057500
TI  - The impact of rumen cannulation on the microbial community of goat rumens as
      measured using 16S rRNA high-throughput sequencing.
AB  - The main objective of this study was to determine the impact of rumen cannulation
      on the microbial community of goat rumens using 16S rRNA high-throughput
      sequencing. Twelve Boer crossbred goats were used in the experiment: six goats
      were surgically fitted with rumen cannula, and the other six were used as
      controls. All goats were fed the same diet for 20 days, after which their rumen
      digesta were sampled once per week for three consecutive weeks. Total microbial
      DNA was extracted from the collected rumen fluid and was used as a template to
      amplify the V4 hypervariable region of the 16S rRNA gene. High-throughput
      sequencing was performed using an Illumina MiSeq platform, and the sequences were
      analyzed primarily using the Quantitative Insights into Microbial Ecology
      pipeline software. The results showed that the Chao 1 index, the observed species
      index and the Shannon-Wiener index were not significantly different (p > 0.05)
      between the two groups. Bacteroidetes, Firmicutes, Tenericutes were the
      predominant phylum in both groups, and their relative abundance was 60.63%,
      29.48%, 2.24% (n = 6, CT group) and 61.17%, 26.92%, 1.66% (n = 6, RC group)
      respectively. At the phylum level, the relative abundance of Proteobacteria was
      significantly higher (p < 0.001) in the microbial communities of RC goats, and
      Planctomycetes and Chloroflexi were significantly lower (p = 0.02). The
      abundances of other phyla were not significantly different between treatments. A
      total of 19 lower-level taxa also exhibited significant differences (p < 0.05) in
      relative abundance between the groups. In addition, there were 18 genera shared
      within the control group, 26 shared within the rumen-cannulated group, and 16
      shared by both groups. Prevotella was the most abundant shared genus, although
      its abundance was not significantly different (p > 0.05) between the groups. In
      conclusion, although the most abundant microbes kept stable, rumen cannulation
      had the potential to significantly change rumen microbial communities in goats.

PMID- 29057501
TI  - Different approaches to heart valve decellularization: A comprehensive overview
      of the past 30 years.
AB  - Xenogeneic decellularized heart valve scaffolds have the potential to overcome
      the limitations of existing bioprosthetic heart valves that have limited duration
      due to calcification and tissue degeneration phenomena. This article presents a
      review of 30 years of decellularization approaches adopted in cardiovascular
      tissue engineering, with a focus on the use, either individually or in
      combination, of different detergents. The safety and efficacy of cell-removal
      procedures are specifically reported and discussed, as well as the structure and
      biomechanics of the treated extracellular matrix (ECM). Detergent residues within
      the ECM, production of hyaluronan fragments, safe removal of cellular debris, and
      the persistence of the alpha-Gal epitope after the decellularization treatments
      are of particular interest as parameters for the identification of the best
      tissue for the manufacture of bioprostheses. Special attention has also been
      given to key factors that should be considered in the manufacture of the next
      generation of xenogeneic bioprostheses, where tissues must retain the ability to
      be remodeled and to grow in weight along with body reshaping.

PMID- 29057503
TI  - Reply to correspondence 'Topical ionic contra-viral therapy comprised of digoxin
      and furosemide as a potential novel treatment approach for common warts '.

PMID- 29057502
TI  - Validation of digital photographic reference scales for evaluating facial aging
      signs.
AB  - BACKGROUND: Validated tools are essential to evaluate facial skin aging for both
      dermatological and cosmetic investigations. While many visual aging scales have
      been developed, few have been validated and none in terms of degree of
      distinguishability (DD). We developed and validated a series of visual scales
      using a novel digital interface for scoring facial skin aging in Caucasian women.
      MATERIALS AND METHODS: Three dermatologists independently established scales for
      12 distinct aging signs from high-definition facial photographs of 400 adult
      women (Fitzpatrick phototypes I-IV) taken under standardized conditions. They
      then selected a consensus scale for each individual sign with a representative
      photo per grade. Scales were integrated into a digital interface allowing
      simultaneous viewing of all grades of each scale alongside the photograph of a
      test subject. Next, scales were validated by a different dermatologist, a general
      practitioner and a non-medical expert skin evaluator using photos of 350 women
      which had not been used for establishing the scales. RESULTS: Kappa estimates
      showed almost perfect agreement for wrinkle and skin aging scales (>=0.85) and
      moderate to substantial agreement for scales relating to color irregularities
      (telangiectasia, solar lentigines, freckles) for both inter- and intra-observer
      reproducibility. Intra-observer DD estimates were mostly high. Non-dermatologists
      performed well on reproducibility for both Kappa (from 0.6 to 0.9) and DD
      estimates. CONCLUSION: Our work demonstrates that the digital interface scales
      for 12 distinct aging features are highly suitable for use in clinical and
      epidemiological studies on skin aging by both dermatologists and non
      dermatologists.

PMID- 29057504
TI  - Speech-language pathology care and short- and long-term outcomes of oropharyngeal
      cancer treatment in the elderly.
AB  - OBJECTIVE: To examine associations between speech-language pathology (SLP) care
      and pretreatment variables, short-term and long-term swallowing and airway
      impairment, and survival in elderly patients treated for oropharyngeal squamous
      cell cancer (SCCA). STUDY DESIGN: Retrospective analysis of Surveillance,
      Epidemiology, and End Results-Medicare data. METHODS: We evaluated longitudinal
      data from 666 patients diagnosed with oropharyngeal SCCA from 2004 to 2007 using
      cross-tabulations, multivariate logistic regression, and survival analysis.
      RESULTS: SLP care was documented in 25% of patients. High-volume hospital care
      (odds ratio (OR) = 3.2 [1.0-10.0]) and dysphagia during treatment (OR = 13.0 [3.6
      47.1]) were the only significant predictors of SLP care during the initial
      treatment period. SLP care was significantly more likely during the first year
      (OR = 5.3 [3.1-9.1]) and second year (OR = 4.5 [2.4-8.2]) following initial
      treatment. Subsequent dysphagia (OR = 32.5 [16.9-62.4]), stricture (OR = 2.2 [1.2
      4.0]), gastrostomy (OR = 1.7 [1.1-2.7]), and tracheostomy tube use (OR = 2.4 [1.2
      4.8]) were significantly associated with long-term SLP care. After controlling
      for patient, tumor, and treatment-related variables, SLP care was associated with
      significant relative attenuation of the OR for dysphagia (93%), stricture (35%),
      weight loss (8%), and airway obstruction (34%). Survival analysis, controlling
      for all other variables, demonstrated improved survival for patients under SLP
      care (hazard ratio = 0.73 [0.57-0.95]). CONCLUSION: SLP care is underutilized in
      elderly oropharyngeal SCCA patients and largely utilized after the onset of
      impaired airway and swallowing function, but is associated with improved
      outcomes. These data suggest a need for treatment guidelines that incorporate the
      routine use of SLP care in this population during the initial treatment period
      and beyond. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1403-1411, 2018.

PMID- 29057505
TI  - Ductal cells of minor salivary glands in Sjogren's syndrome express LINE-1 ORF2p
      and APOBEC3B.
AB  - BACKGROUND: Type I interferon activation is a hallmark event in Sjogren's
      syndrome. L1 retroelements stimulate plasmacytoid dendritic cells, activating the
      type I interferons, and are regulated by various mechanisms, including the
      APOBEC3 deaminases. As L1s are potential trigger factors in autoimmunity, we
      aimed to investigate the immunohistochemical localization of L1 ORF2p and its
      inhibitor APOBEC3B protein in minor salivary glands of Sjogren's syndrome
      patients. METHODS: Twenty minor salivary gland-tissue samples from 20 Sjogren's
      syndrome patients, classified according to Tarpley's histological criteria, and
      10 controls were evaluated for L1 ORF2p and APOBEC3B expression via
      immunohistochemistry. RESULTS: L1 ORF2p was expressed in 17/20 SS patients and
      all controls. APOBEC3B expression was observed in 15/20 Sjogren's syndrome
      patients, 5/5 chronic sialadenitis, and 3/5 normal minor salivary glands. Both
      antibodies stained the cytoplasm of the ductal epithelial cells. Negative
      staining was observed in the acinar cells. L1 ORF2p-positive immunostaining was
      significantly lower in Tarpley IV Sjogren's syndrome patients than controls (P =
      .039), and APOBEC3B-positive staining was significantly lower in Tarpley I
      compared to Tarpley II Sjogren's syndrome patients (P = .008) and controls (P =
      .035). CONCLUSIONS: L1 ORF2p and APOBEC3B are expressed in the ductal epithelial
      cells of minor salivary glands that are among the key targets in Sjogren's
      syndrome. L1 ORF2p expression may promote the L1 ability to act as an intrinsic
      antigen in Sjogren's syndrome. The potential future use of L1 ORF2-reverse
      transcriptase inhibitors in autoimmunity supports further investigation of L1
      epigenetic regulation by APOBEC3 enzymes.

PMID- 29057506
TI  - Reproducibility of measurement of skin melanin, total hemoglobin, and oxygen
      saturation.

PMID- 29057507
TI  - A feature fusion system for basal cell carcinoma detection through data-driven
      feature learning and patient profile.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer, which is
      highly damaging in its advanced stages. Computer-aided techniques provide a
      feasible option for early detection of BCC. However, automated BCC detection
      techniques immensely rely on handcrafting high-level precise features. Such
      features are not only computationally complex to design but can also represent a
      very limited aspect of the lesion characteristics. This paper proposes an
      automated BCC detection technique that directly learns the features from image
      data, eliminating the need for handcrafted feature design. METHODS: The proposed
      method is composed of 2 parts. First, an unsupervised feature learning framework
      is proposed which attempts to learn hidden characteristics of the data including
      vascular patterns directly from the images. This is done through the design of a
      sparse autoencoder (SAE). After the unsupervised learning, we treat each of the
      learned kernel weights of the SAE as a filter. Convolving each filter with the
      lesion image yields a feature map. Feature maps are condensed to reduce the
      dimensionality and are further integrated with patient profile information. The
      overall features are then fed into a softmax classifier for BCC classification.
      RESULTS: On a set of 1199 BCC images, the proposed framework achieved an area
      under the curve of 91.1%, while the visualization of learned features confirmed
      meaningful clinical interpretation of the features. CONCLUSION: The proposed
      framework provides a non-invasive fast BCC detection tool that incorporates both
      dermoscopic lesional features and clinical patient information, without the need
      for complex handcrafted feature extraction.

PMID- 29057508
TI  - Impact of antiviral prophylaxis in adults Epstein-Barr Virus-seronegative kidney
      recipients on early and late post-transplantation lymphoproliferative disorder
      onset: a retrospective cohort study.
AB  - Post-transplantation lymphoproliferative disorder (PTLD) pathogenesis is related
      to EBV infection. Mismatch with the donor (EBV D+/R-) is the main risk factor for
      both early PTLD (<1 year post-transplantation) and late (>1 year). In these at
      risk patients, the role of antiviral prophylaxis for preventing PTLD remains
      controversial. We analyzed the impact of antiviral drugs given to prevent CMV
      disease in a monocentric retrospective cohort of 73 adult kidney or kidney
      pancreas EBV-seronegative recipients, transplanted between 01/01/2000 and
      01/01/2016. Thirty-seven (50.7%, prophylaxis group) received (val-)aciclovir or
      (val-)ganciclovir for 3-6 months and 36 (49.3%, no-prophylaxis group) received no
      prophylaxis. Mean follow-up was 69 +/- 7.2 months in the prophylaxis group and 91
      +/- 10.3 months in the no-prophylaxis group. Monitoring of EBV PCR revealed that
      prophylaxis delayed primary infection at 100 days (43% vs. 84%, P = 0.02). Early
      PTLD incidence was not different between groups (4/37 vs. 4/36, P = 0.99).
      Concerning late events, EBV-related neoplasia incidence was significantly lower
      in treated patients among whom no cases were observed, while in the no
      prophylaxis group 6 cases were reported (P = 0.02). Despite a weak level of
      evidence our study suggests that antiviral prophylaxis could prevent late onset
      PTLD.

PMID- 29057509
TI  - The relationship between skin function, barrier properties, and body-dependent
      factors.
AB  - BACKGROUND: Skin is a multilayer interface between the body and the environment,
      responsible for many important functions, such as temperature regulation, water
      transport, sensation, and protection from external triggers. OBJECTIVES: This
      paper provides an overview of principal factors that influence human skin and
      describes the diversity of skin characteristics, its causes and possible
      consequences. It also discusses limitations in the barrier function of the skin,
      describing mechanisms of absorption. METHODS: There are a number of in vivo
      investigations focusing on the diversity of human skin characteristics with
      reference to barrier properties and body-dependent factors. RESULTS: Skin
      properties vary among individuals of different age, gender, ethnicity, and skin
      types. In addition, skin characteristics differ depending on the body site and
      can be influenced by the body-mass index and lifestyle. Although one of the main
      functions of the skin is to act as a barrier, absorption of some substances
      remains possible. CONCLUSIONS: Various factors can alter human skin properties,
      which can be reflected in skin function and the quality of everyday life. Skin
      properties and function are strongly interlinked.

PMID- 29057511
TI  - Improved survival of men with metastatic prostate cancer treated with androgen
      deprivation therapy plus radiotherapy to the prostate.

PMID- 29057510
TI  - Release of pig leukocytes and reduced human NK cell recruitment during ex vivo
      perfusion of HLA-E/human CD46 double-transgenic pig limbs with human blood.
AB  - BACKGROUND: In pig-to-human xenotransplantation, interactions between human
      natural killer (NK) cells and porcine endothelial cells (pEC) are characterized
      by recruitment and cytotoxicity. Protection from xenogeneic NK cytotoxicity can
      be achieved in vitro by the expression of the non-classical human leukocyte
      antigen-E (HLA-E) on pEC. Thus, the aim of this study was to analyze NK cell
      responses to vascularized xenografts using an ex vivo perfusion system of pig
      limbs with human blood. METHODS: Six pig forelimbs per group, respectively,
      stemming from either wild-type (wt) or HLA-E/hCD46 double-transgenic (tg)
      animals, were perfused ex vivo with heparinized human blood for 12 hours. Blood
      samples were collected at defined time intervals, cell numbers counted, and
      peripheral blood mononuclear cells analyzed for phenotype by flow cytometry.
      Muscle biopsies were analyzed for NK cell infiltration. In vitro NK cytotoxicity
      assays were performed using pEC derived from wt and tg animals as target cells.
      RESULTS: Ex vivo, a strong reduction in circulating human CD45 leukocytes was
      observed after 60 minutes of xenoperfusion in both wt and tg limb groups. NK cell
      numbers dropped significantly. Within the first 10 minutes, the decrease in NK
      cells was more significant in the wt limb perfusions as compared to tg limbs.
      Immunohistology of biopsies taken after 12 hours showed less NK cell tissue
      infiltration in the tg limbs. In vitro, NK cytotoxicity against hCD46 single tg
      pEC and wt pEC was similar, while lysis of double tg HLA-E/hCD46 pEC was
      significantly reduced. Finally, circulating cells of pig origin were observed
      during the ex vivo xenoperfusions. These cells expressed phenotypes mainly of
      monocytes, B and T lymphocytes, NK cells, as well as some activated endothelial
      cells. CONCLUSIONS: Ex vivo perfusion of pig forelimbs using whole human blood
      represents a powerful tool to study humoral and early cell-mediated rejection
      mechanisms of vascularized pig-to-human xenotransplantation, although there are
      several limitations of the model. Here, we show that (i) transgenic expression of
      HLA-E/hCD46 in pig limbs provides partial protection from human NK cell-mediated
      xeno responses and (ii) the emergence of a pig cell population during
      xenoperfusions with implications for the immunogenicity of xenografts.

PMID- 29057512
TI  - Induction of porcine-specific regulatory T cells with high specificity and
      expression of IL-10 and TGF-beta1 using baboon-derived tolerogenic dendritic
      cells.
AB  - BACKGROUND: Regulatory T cells (Treg) play an important role in maintenance of
      homeostasis in vivo. Treg application to alleviate allo-organ rejection is being
      studied extensively. However, natural Treg (nTreg) expansion in vitro is
      laborious and expensive. Antigen-specific Treg are more effective and require
      lower cell numbers than use of nTreg for immune control. The baboon, as a non
      human primate experimental animal model, is widely used in xenotransplantation
      research. An effective method to generate baboon xeno-specific Treg would benefit
      research on immune tolerance in xenotransplantation using this model system.
      METHOD: Baboon tolerogenic dendritic cells (tolDC) were generated in 3 days from
      monocytes isolated from baboon peripheral blood mononuclear cells in medium
      supplemented with anti-inflammatory cytokines. After loading with porcine
      specific (PS) in vitro-transcribed RNA (ivtRNA), tolDC were used to induce CD4+ T
      cells to become porcine-specific Treg (PSTreg) in cocultures supplemented with IL
      2 and rapamycin for 10 days. Anti-inflammatory and inflammatory cytokine
      expression was evaluated at the mRNA and protein levels in both baboon tolDC and
      PSTreg. Functional assays, suppression of activation markers on porcine-specific
      effector T cells (PSTeff) and inhibition of PSTeff proliferation, were used to
      test PSTreg specificity. RESULTS: TolDC generated with this method exhibited a
      tolerogenic phenotype, expressed CCR7 and produced high levels of IL-10 and TGF
      beta1, whereas IL-12p40 and IFN-gamma were not expressed. PSTreg were
      successfully generated in cocultures of CD4+ T cells and PS ivtRNA-loaded tolDC.
      They exhibited a CD3+  CD4+  CD25+  CD127low/-  CD45RAlow  Foxp3+ phenotype and
      were characterized by high expression of IL-10 and TGF-beta1 mRNA and protein.
      They showed upregulated expression of EBI3 and GARP mRNA. PSTreg exhibited highly
      suppressive effects toward PSTeff, secreting high amounts of IL-10 and TGF-beta1
      cytokine upon interaction with PSTeff and suppressing IFN-gamma expression on
      PSTeff. CONCLUSION: In this study, a fast 3-day method to generate baboon-derived
      tolDC is provided that allows subsequent induction of PSTreg displaying high
      porcine-antigen specificity and expression of IL-10 and TGF-beta1. Porcine
      specific baboon Treg can be used in porcine solid organ or cell
      xenotransplantation studies through adoptive cell transfer into host baboons.

PMID- 29057513
TI  - Optical coherence tomography for margin definition of basal cell carcinoma before
      micrographic surgery-recommendations regarding the marking and scanning
      technique.
AB  - BACKGROUND/PURPOSE: Mohs Micrographic Surgery (MMS) is the preferred therapeutic
      treatment for high-risk basal cell carcinoma (BCC). Optical Coherence Tomography
      (OCT) is a non-invasive imaging technique that enables the diagnosis of BCC. We
      thought to determine the margins of BCCs with OCT, prior to MMS, to reduce the
      number of surgical steps. METHODS: Different permanent markers were tested on the
      skin regarding line width, resistance against disinfection and brightness in the
      OCT image. The visible tumor margins of BCCs were defined by dermoscopy, adding a
      safety margin of 2 mm and labeled using the selected pen, causing a signal shadow
      in OCT. Scans of the center and of entire margin were performed. If parts of the
      BCC were visible outside the margin, another 2 mm were added and the scan was
      repeated until the tissue outside the labeling looked tumor free. RESULTS: Eight
      out of ten BCCs were totally excised in a single stage when margin delineation
      was done by OCT. Macroscopic margins were enlarged after OCT scanning in four
      patients, saving further stages of MMS. CONCLUSION: OCT may help to better define
      the microscopic dimensions of BCCs and therefore reduce the number of stages of
      MMS.

PMID- 29057514
TI  - Optical coherence tomography: An efficient imaging method for the visualization
      of human epidermis orientation.
AB  - Recently, it has been shown that epidermal sheets taken from suction blisters are
      very appropriate skin samples for Multi-Photon (MP) microscopy. However, we
      observed that image quality was much better when the sample was visualized
      through the basale side. Thus, the epidermis orientation needs to be controlled
      before MP imaging. We observed that the use of standard laboratory binoculars led
      to a high rate of false results. In this context, we showed that optical
      coherence tomography provided clear images of the epidermis orientation without
      loss of sample integrity and thus represents an effective technique before slide
      sealing and MP analysis.

PMID- 29057515
TI  - Spread of fluid: Role of tip configurations in needles.
AB  - BACKGROUND/PURPOSE: During the injection of a fluid in a tissue model, the fluid
      might be affected by the needle tip configuration and the number of channels.
      Thus, the objective of the present work is to observe the influence of different
      needle tips and number of channels on the spread of a fluid. METHODS: Fluid
      distribution data were obtained after injecting 0.3 mL of fluid into a foamed
      polymer model with a velocity of 2 mm/s. The spread area and the depth were
      determined for 3 different types of hypodermic needles: Single channel needles
      with bevel tip and blunt tip and a needle with conical tip and 3 internal
      channels. RESULTS: The bevel tip provides a higher spread in the direction where
      the bevel points and reaches larger depths than the other two needles. The spread
      for the blunt tip and the polymer needle is equally distributed on both sides of
      the needle. The largest horizontal area around the tip is achieved by the 3
      channel needle. CONCLUSION: The tip configuration and number of channels have an
      influence on the distribution of fluid. The bevelled needle directs the fluid and
      reaches larger depths compared with the 3-channel needle that gets more
      horizontal spread.

PMID- 29057516
TI  - Porphyromonas gingivalis lipopolysaccharide induces over production of CC
      chemokine ligand 2 via toll-like receptor-4 in oral lichen planus.
AB  - BACKGROUND: We recently reported that the CC chemokine ligand 2 (CCL2)-CC
      receptor 2 (CCR2) axis was involved in the pathogenesis of oral lichen planus
      (OLP). However, the exact mechanism for the high expression of CCL2 in OLP
      specimens is not clear. Therefore, this study was designed to investigate the
      potential role of the toll-like receptor 4 (TLR-4) pathway in overproduction of
      CCL2 in OLP lesions. METHODS: Immunohistochemical staining and real-time RT-PCR
      were used to detect TLR-4, CCL2, and CCR2 expression in OLP lesions. Then,
      gingival epithelial cells from OLP lesions were established and treated with
      Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). CCL2
      expression in epithelial cells was determined by Western blotting and real-time
      RT-PCR. In some experiments, TAK-242, a specific inhibitor of TLR-4, was used to
      block the TLR-4 pathway before cells were stimulated with LPS. RESULTS: We found
      that TLR-4 was significantly increased in the epithelium of OLP specimens,
      compared with controls. Moreover, LPS can induce the over production of CCL2 in
      epithelial cells of OLP, in vitro. TAK-242 effectively eliminated the increase in
      CCL2 expression induced by LPS by blocking the TLR-4/NF-kappaB pathway. In
      addition, we again confirmed that expression of CCL2 and CCR2 was increased in
      OLP specimens. CONCLUSION: Increased TLR-4 expression contributes to the
      upregulated expression of CCL2 in the epithelium of OLP lesions, which suggests
      that oral bacteria participate in the pathogenesis of OLP via the TLR-4 pathway.

PMID- 29057517
TI  - The indane diastereoisomers, PH2 and PH5: divergence between their effects in
      delayed-type hypersensitivity models and a model of colitis.
AB  - OBJECTIVES: Compounds PH2 and PH5 are distereoisomers of novel indane compounds,
      synthesised as analogues of secondary metabolites of the fern, Onychium. In this
      study, we compare their effects on a variety of inflammatory models. METHODS: In
      an effort to extend our knowledge of their anti-inflammatory profile, we have
      investigated their activity in two models of delayed-type hypersensitivity (DTH);
      the methylated bovine serum albumin model (mBSA) and the oxazolone contact
      hypersensitivity (CHS) model, on IL2 release from Jurkat cells and in the dextran
      sulphate sodium (DSS) murine model of inflammatory bowel disease. KEY FINDINGS:
      Both diastereoisomers are equipotent in reducing paw swelling in the mBSA model
      and in inhibiting interleukin (IL) 2 release from Jurkat cells. They are equally
      ineffective in the oxazolone contact hypersensitivity model (CHS). Only the
      diastereoisomer, PH5, protects against DSS-induced colitis and of its two
      enantiomers, only the S,S-enantiomer, PH22, possesses this activity. PH2 is
      ineffective in the DSS model. CONCLUSIONS: The results suggest that the
      beneficial effect of PH5, and its enantiomer PH22, in the DSS model is a
      consequence of an action on a target specific to the colitis model. The
      implications of such data suggest an unknown target in this disease model that
      may be exploited to therapeutic advantage.

PMID- 29057518
TI  - Tracheal dilatation as sign of fetal airway obstruction in case of oral cavity
      tumor.

PMID- 29057519
TI  - Progress and Opportunities in Soft Photonics and Biologically Inspired Optics.
AB  - Optical components made fully or partially from reconfigurable, stimuli
      responsive, soft solids or fluids-collectively referred to as soft photonics-are
      poised to form the platform for tunable optical devices with unprecedented
      functionality and performance characteristics. Currently, however, soft solid and
      fluid material systems still represent an underutilized class of materials in the
      optical engineers' toolbox. This is in part due to challenges in fabrication,
      integration, and structural control on the nano- and microscale associated with
      the application of soft components in optics. These challenges might be addressed
      with the help of a resourceful ally: nature. Organisms from many different phyla
      have evolved an impressive arsenal of light manipulation strategies that rely on
      the ability to generate and dynamically reconfigure hierarchically structured,
      complex optical material designs, often involving soft or fluid components. A
      comprehensive understanding of design concepts, structure formation principles,
      material integration, and control mechanisms employed in biological photonic
      systems will allow this study to challenge current paradigms in optical
      technology. This review provides an overview of recent developments in the fields
      of soft photonics and biologically inspired optics, emphasizes the ties between
      the two fields, and outlines future opportunities that result from advancements
      in soft and bioinspired photonics.

PMID- 29057520
TI  - Editorial: Minding the gap - research on sexual minority and gender nonconforming
      children and adolescents.
AB  - There is often a gap between politics and science, but the influence across the
      gap is bidirectional. This editorial considers a longitudinal, community-based
      sample of children and adolescents and asks about risks from early childhood
      gender non-conformity and adolescent reported sexual minority status for
      subsequent anxiety disorders. It is especially valuable to have longitudinal data
      from a non-referred sample to address questions of risk, and the investigators
      must be complemented for having foresight about these questions twenty years ago.
      The topics of our investigations are informed and motivated by cultural
      assumptions, pressures and conflicts. In the example discussed, transgender
      people are not new, but research on their development is fairly recent, as they
      are culturally now more accepted as different rather than pathological. Research
      findings also matter to the culture. Dropping homosexuality as a mental disorder
      in formal nosologies occurred with significant scientific substantiation. The
      value of this research to enhance clinical care and offer informed parental
      guidance about children of a minority status cannot be overemphasized.

PMID- 29057521
TI  - Commentary: The dynamic panel model: a promising approach to clarify sources of
      influence in developmental psychopathology - a commentary on Wichstrom et al.
      (2017).
AB  - In their study, Wichstrom et al. (2017) have proposed a novel groundbreaking
      approach for developmental psychopathology that undoubtedly will inspire other
      research. Applying the dynamic panel model (DPM), the authors were able to show
      that within-disorder (homotypic) and between-disorder (heterotypic) continuities
      of psychiatric symptoms are mostly due to unmeasured time-invariant factors while
      only few effects of earlier symptoms on later symptoms remained significant after
      accounting for these factors. The DPM calls for future applications of this
      approach to samples across different countries, diverse developmental phases, and
      in various settings - community samples and clinical samples alike.

PMID- 29057522
TI  - Intensive prolonged exposure treatment for adolescent complex posttraumatic
      stress disorder: a single-trial design.
AB  - BACKGROUND: The current study evaluated the effectiveness and safety of intensive
      prolonged exposure (PE) targeting adolescent patients with complex posttraumatic
      stress disorder (PTSD) and comorbid disorders following multiple interpersonal
      trauma. METHODS: Ten adolescents meeting full diagnostic criteria for PTSD were
      recruited from a specialized outpatient mental health clinic and offered a
      standardized intensive PE. The intensive PE consisted of three daily 90-min
      exposure sessions delivered on five consecutive weekdays, followed by 3 weekly 90
      min booster sessions. In a single-trial design, the participants were randomly
      allocated to one of five baseline lengths (4-8 weeks) before starting the
      intensive PE. Before, during, and after intensive PE completion, self-reported
      PTSD symptom severity was assessed weekly as a primary outcome (a total of 21
      measurements). Furthermore, clinician-administered PTSD diagnostic status and
      symptom severity (primary outcome), as well as self-reported comorbid symptoms
      (secondary outcomes), were assessed at four single time points (baseline-to-6
      month follow-up). RESULTS: Time-series analyses showed that self-reported PTSD
      symptom severity significantly declined following treatment (p = .002). Pre
      postgroup analyses demonstrated significant reductions of clinician-administered
      PTSD symptom severity and self-reported comorbidity that persisted during the 3-
      and 6-month follow-ups (all ps < .05), where 80% of adolescents had reached
      diagnostic remission of PTSD. There was neither treatment dropout nor any adverse
      events. CONCLUSIONS: The results of this first proof of concept trial suggest
      that intensive PE can be effective and safe in an adolescent population with
      complex PTSD, although the gains achieved need to be confirmed in a randomized
      controlled trial.

PMID- 29057523
TI  - Ageing-related changes in the cortical processing of otolith information in
      humans.
AB  - Acoustic short tone bursts (STB) trigger ocular and cervical vestibular-evoked
      myogenic potentials (oVEMPs/cVEMPs) by activating irregular otolith afferents.
      Simultaneously, STBs introduce an artificial net acceleration signal of otolith
      origin into the vestibular network. VEMP parameters as diagnostic otolith
      processing markers have been shown to decline after the age of thirty. To
      delineate the differential effects of healthy ageing on the cortical vestibular
      subnetwork processing otolith information, we measured cVEMPs and the
      differential effects of unilateral STB in three age groups (20-40, 40-60 and 60+;
      n = 42) using functional neuroimaging. STB evoked responses in the main
      vestibular hubs in the parieto-opercular cortex. Whereas cVEMP amplitudes
      declined linearly with age, analysis of the BOLD response size depicted a u
      shaped curve. Vestibular perception of the otolith stimulus on the other hand
      remained unchanged with age. Therefore, we propose that the comparably larger
      BOLD responses past the age of sixty could reflect a mechanism of central
      sensitisation for otolith perception to counterbalance the concurrent peripheral
      vestibular and somatosensory function decline.

PMID- 29057524
TI  - Organ transplantation from "increased infectious risk donors": the experience of
      the Nord Italia Transplant program - A retrospective study.
AB  - The purpose of this study was to assess the safety and the clinical outcome
      associated with organ transplantation from increased infectious risk donors
      (IRD). We retrospectively identified all adult deceased IRD referred to the Nord
      Italia Transplant program coordinating center from November 2006 to November
      2011. All potential donors were screened for social risk factors that may
      increase the risk of donor-derived infection with human immunodeficiency (HIV),
      hepatitis B virus (HBV), or hepatitis C virus (HCV). All recipients were followed
      monthly for the first 6 months post-transplant. A total of 86 potential IRD were
      identified during the study period. Three hundred and seventy-nine organs from
      IRD were offered to the transplant centers, but only 185 (48.8%) were used for
      transplantation. Organs from IRD were transplanted into 174 recipients. The
      complete follow-up data were available for 152 of 174 (87.3%) recipients. During
      a mean follow-up of 11.7 months (median 12; range 2.4-12), no transmission of
      HIV, HBV, or syphilis was documented by serology and nucleic acid testing (NAT)
      testing. Two patients transplanted with organs from HCV-RNA-positive donors, as
      expected, developed post-transplant HCV infection. In conclusion, the use of
      organs from IRD was associated with a safe increase in the transplant procedures
      in our country.

PMID- 29057525
TI  - Direct Aldehyde Csp2 -H Functionalization through Visible-Light-Mediated
      Photoredox Catalysis.
AB  - The development of methods for carbon-carbon bond formation under benign
      conditions is an ongoing challenge for synthetic chemists. In recent years there
      has been considerable interest in using selective C-H activation as a direct
      route for generating reactive intermediates. Herein, the use of visible-light
      mediated dual photoredox organocatalysis as a mild and effective method for Csp2 
      H activation of aldehydes is reported, resulting in the generation of acyl
      radicals. These nucleophilic acyl radical species can undergo either addition to
      electrophilic alkenes or nickel-catalyzed cross-coupling reactions to provide a
      quick access to broad range of unsymmetrical ketones, which are abundantly found
      in many organic building blocks.

PMID- 29057526
TI  - Electrochemical and Reactivity Studies of N->Sn Coordinated Distannynes.
AB  - Studies are focused on the redox potentials of N->Sn coordinated distannnynes {L1
      3 Sn}2 (L1 =1, L2 =2 and L3 =3, in which L1 is [C6 H3 -2,6-(Me2 NCH2 )2 ]- , L2
      is [C6 H2 -2,4-tBu2 -6-(Et2 NCH2 )]- and L3 is [C6 H2 -2,4-tBu2 -6-(DippN=CH)]- ;
      Dipp=2,6-diisopropylphenyl), containing the tin atom in oxidation state +I.
      Distannynes 1-3 were used as ligands for transition metals, and complexes [{L1
      Sn}2 ?Fe(CO)4 ] (4) and [{L2 Sn}2 ?Fe(CO)4 ] (5) were prepared. The set of N->Sn
      coordinated distannynes 1-5 was studied by cyclic voltammetry measurements and
      the oxidation potentials of tin atoms in 1-5 were determined. The redox
      potentials are influenced by either ligands L1-3 or SnI ->Fe coordination.
      Oxidation reactions of 1-3 were also studied. The reaction of 2 with (2,2,6,6
      tetramethylpiperidin-1-yl)oxyl (TEMPO) provided mixed organotin oxide {(L2
      SnO)(L2 )Sn(MU-O)}2 (6) as a consequence of the instability of the expected {L2
      Sn?TEMPO} complex. To support this proposed mechanism, the N->Ge coordinated
      digermyne {L2 Ge}2 (7) was prepared. The reaction of 7 with TEMPO provided the
      expected complex {L2 Ge?TEMPO} (8).

PMID- 29057528
TI  - Author's reply to Grati and Benn.

PMID- 29057527
TI  - Exploring the genomic basis of early childhood caries: a pilot study.
AB  - OBJECTIVE: A genetic component in early childhood caries (ECC) is theorized, but
      no genome-wide investigations of ECC have been conducted. This pilot study is
      part of a long-term research program aimed to: (1) determine the proportion of
      ECC variance attributable to the human genome and (2) identify ECC-associated
      genetic loci. METHODS: The study's community-based sample comprised 212 children
      (mean age=39 months; range = 30-52 months; males = 55%; Hispanic/Latino = 35%,
      African-American = 32%; American Academy of Pediatric Dentistry definition of ECC
      prevalence = 38%). Approximately 2.4 million single nucleotide polymorphisms
      (SNPs) were genotyped using DNA purified from saliva. A P < 5 * 10-8 criterion
      was used for genome-wide significance. SNPs with P < 5 * 10-5 were followed-up in
      three independent cohorts of 921 preschool-age children with similar ECC
      prevalence. RESULTS: SNPs with minor allele frequency >=5% explained 52%
      (standard error = 54%) of ECC variance (one-sided P = 0.03). Unsurprisingly,
      given the pilot's small sample size, no genome-wide significant associations were
      found. An intergenic locus on 4q32 (rs4690994) displayed the strongest
      association with ECC [P = 2.3 * 10-6 ; odds ratio (OR) = 3.5; 95% confidence
      interval (CI) = 2.1-5.9]. Thirteen loci with suggestive associations were
      followed-up - none showed evidence of association in the replication samples.
      CONCLUSION: This study's findings support a heritable component of ECC and
      demonstrate the feasibility of conducting genomics studies among preschool-age
      children.

PMID- 29057529
TI  - Comment on "The clinical utility of genome-wide non invasive prenatal screening".

PMID- 29057530
TI  - Comment on "Whole exome sequencing and array-based molecular karyotyping as aids
      to prenatal diagnosis in fetuses with suspected Simpson-Golabi-Behmel syndrome".

PMID- 29057531
TI  - The spatio-temporal profile of multisensory integration.
AB  - Task-irrelevant visual stimuli can enhance auditory perception. However, while
      there is some neurophysiological evidence for mechanisms that underlie the
      phenomenon, the neural basis of visually induced effects on auditory perception
      remains unknown. Combining fMRI and EEG with psychophysical measurements in two
      independent studies, we identified the neural underpinnings and temporal dynamics
      of visually induced auditory enhancement. Lower- and higher-intensity sounds were
      paired with a non-informative visual stimulus, while participants performed an
      auditory detection task. Behaviourally, visual co-stimulation enhanced auditory
      sensitivity. Using fMRI, enhanced BOLD signals were observed in primary auditory
      cortex for low-intensity audiovisual stimuli which scaled with subject-specific
      enhancement in perceptual sensitivity. Concordantly, a modulation of event
      related potentials could already be observed over frontal electrodes at an early
      latency (30-80 ms), which again scaled with subject-specific behavioural
      benefits. Later modulations starting around 280 ms, that is in the time range of
      the P3, did not fit this pattern of brain-behaviour correspondence. Hence, the
      latency of the corresponding fMRI-EEG brain-behaviour modulation points at an
      early interplay of visual and auditory signals in low-level auditory cortex,
      potentially mediated by crosstalk at the level of the thalamus. However, fMRI
      signals in primary auditory cortex, auditory thalamus and the P50 for higher
      intensity auditory stimuli were also elevated by visual co-stimulation (in the
      absence of any behavioural effect) suggesting a general, intensity-independent
      integration mechanism. We propose that this automatic interaction occurs at the
      level of the thalamus and might signify a first step of audiovisual interplay
      necessary for visually induced perceptual enhancement of auditory perception.

PMID- 29057532
TI  - Lobular patterns of cerebellar resting-state connectivity in adults with Autism
      Spectrum Disorder.
AB  - Autism spectrum disorder is a neurodevelopmental disorder characterized by core
      deficits in social functioning. Core autistics traits refer to poor social and
      imagination skills, poor attention-switching/strong focus of attention,
      exceptional attention to detail, as expressed by the autism-spectrum quotient.
      Over the years, the importance of the cerebellum in the aetiology of autism
      spectrum disorder has been acknowledged. Neuroimaging studies have provided a
      strong support to this view, showing both structural and functional connectivity
      alterations to affect the cerebellum in autism spectrum disorder. According to
      the underconnectivity theory, disrupted connectivity within cerebello-cerebral
      networks has been specifically implicated in the aetiology of autism spectrum
      disorder. However, inconsistent results have been generated across studies. In
      this study, an integrated approach has been used in a selected population of
      adults with autism spectrum disorder to analyse both cerebellar morphometry and
      functional connectivity. In individuals with autism spectrum disorder, a
      decreased cerebellar grey matter volume affected the right Crus II, a region
      showing extensive connections with cerebral areas related to social functions.
      This grey matter reduction correlates with the degree of autistic traits as
      measured by autism-spectrum quotient. Interestingly, altered functional
      connectivity was found between the reduced cerebellar Crus II and contralateral
      cerebral regions, such as frontal and temporal areas. Overall, the present data
      suggest that adults with autism spectrum disorder present with specific
      cerebellar structural alterations that may affect functional connectivity within
      cerebello-cerebral modules relevant to social processing and account for core
      autistics traits.

PMID- 29057534
TI  - Recent Progress in the Surface Modification of Photoelectrodes toward Efficient
      and Stable Overall Water Splitting.
AB  - Photoelectrochemical (PEC) water splitting using a combination of a photocathode
      and photoanode is one of the most promising methods of producing hydrogen from
      water employing sunlight. Recent reports have shown that surface modification of
      the photoelectrodes dramatically improves their PEC performance. Bare
      photoelectrodes often exhibit insufficient depletion regions, undesired surface
      states and/or degradation due to photocorrosion. It has been demonstrated that
      surface modifications can tune the flat-band potentials, band-edge potentials,
      surface states and chemical stabilities of these electrodes and thus improve
      quantum efficiency, onset potential and durability. This review describes in
      detail the various surface modification materials that have been developed to
      date, and the functions of these modifiers. This information is expected to
      provide guidelines for the future development of photoelectrodes capable of
      highly efficient and stable PEC water splitting.

PMID- 29057533
TI  - Catalytic Carbon-Chlorine Bond Activation by Selenium-Based Chalcogen Bond
      Donors.
AB  - Chalcogen bonding is a noncovalent interaction based on electrophilic chalcogen
      substituents, which shares many similarities with the more well-known hydrogen
      and halogen bonding. Herein, the first application of selenium-based chalcogen
      bond donors in organocatalysis is described. Cationic bifunctionalized
      organoselenium compounds activate the carbon-chlorine bond of 1-chloroisochroman
      in a benchmark reaction. While imidazolium-based derivatives showed no noticeable
      activation, benzimidazolium backbones yielded potent catalysts. In all cases, syn
      isomers were markedly more active, presumably due to bidentate coordination,
      which was confirmed by DFT calculations. Comparison experiments with the
      corresponding non-selenated as well as the non-cationic reference compounds
      clearly indicate that the catalytic activity can be ascribed to chalcogen
      bonding. The rate acceleration by the catalyst-compared to the non-selenated
      derivative-was about 10 fold.

PMID- 29057535
TI  - Validity of ISUOG basic training test.

PMID- 29057536
TI  - The combination of plasma fibrinogen and neutrophil lymphocyte ratio (F-NLR) is a
      predictive factor in patients with resectable non small cell lung cancer.
AB  - The prognostic value of inflammation indexes in non small cell lung cancer
      (NSCLC) was not established. Therefore, we assessed the clinical applicability of
      the F-NLR score, which is based on fibrinogen (F) and the neutrophil-lymphocyte
      ratio (NLR), and the glasgow prognostic score (GPS) to predict the prognoses of
      NSCLC patients. We retrospectively identified 515 patients with stage I/II/IIIA
      who underwent surgery at our institution, and evaluated their preoperative serum
      levels of CRP, albumin, fibrinogen, neutrophil count, and the lymphocyte count.
      The cut-off values of the fibrinogen level and NLR were determined with receiver
      operating characteristic (ROC) curve. GPS was classified into three groups as
      previously described. The disease free survival (DFS) and overall survival (OS)
      were calculated by the Kaplan-Meier method. Categorical variables were compared
      using the chi2 test. Survival curves were estimated using the Kaplan-Meier
      method, and the Cox proportional hazard model was used to assess the prognostic
      factors. The F-NLR was significantly associated with sex (p = 0.000), smoking
      history (p = 0.014), lesion type (p = 0.000), histologic type (p = 0.000), T
      stage (p = 0.000), venous invasion (p = 0.000), lymphatic invasion (p = 0.000),
      and TNM stage (p = 0.000). The 5-year DFS rates in F-NLR groups 0, 1, and 2 were
      46.7%, 36.4%, 30.1%, respectively (p = 0.000), and the 5-year overall survival
      (OS) rates in the above three groups were 52.0%, 39.8%, 32.1%, respectively (p =
      0.000). Multivariate analysis showed that venous invasion (p = 0.036), lymph node
      metastasis (p = 0.000), and F-NLR (p = 0.034) were independent prognostic factors
      for DFS. Age (p = 0.015), venous invasion (p = 0.024), lymph node metastasis (p =
      0.000), and F-NLR (p = 0.019) were independent prognostic factors for OS. Thus, F
      NLR was the independent prognostic factor for both the DFS and OS. And patients
      with a high-risk preoperative F-NLR group may benefit from adjuvant therapy by
      subgroup analysis. Our results demonstrated that F-NLR, a novel inflammation
      based grading system, as well as the GPS, appeared to have value as a promising
      clinical predictor of the prognosis for the resectable non small cell lung cancer
      patients.

PMID- 29057537
TI  - CpG oligodeoxynucleotide preconditioning improves cardiac function after
      myocardial infarction via modulation of energy metabolism and angiogenesis.
AB  - Unmethylated CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9)
      ligand, has been shown to protect against myocardial ischemia/reperfusion injury.
      However, the potential effects of CpG-ODN on myocardial infarction (MI) induced
      by persistent ischemia remains unclear. Here, we investigated whether and how CpG
      ODN preconditioning protects against MI in mice. C57BL/6 mice were treated with
      CpG-ODN by i.p. injection 2 hr prior to MI induction, and cardiac function, and
      histology were analyzed 2 weeks after MI. Both 1826-CpG and KSK-CpG
      preconditioning significantly improved the left ventricular (LV) ejection
      fraction (LVEF) and LV fractional shortening (LVFS) when compared with non-CpG
      controls. Histological analysis further confirmed the cardioprotection of CpG-ODN
      preconditioning. In vitro studies further demonstrated that CpG-ODN
      preconditioning increases cardiomyocyte survival under hypoxic/ischemic
      conditions by enhancing stress tolerance through TLR9-mediated inhibition of the
      SERCA2/ATP and activation of AMPK pathways. Moreover, CpG-ODN preconditioning
      significantly increased angiogenesis in the infarcted myocardium compared with
      non-CpG. However, persistent TLR9 activation mediated by lentiviral infection
      failed to improve cardiac function after MI. Although CpG-ODN preconditioning
      increased angiogenesis in vitro, both the persistent stimulation of CpG-ODN and
      stable overexpression of TLR9 suppressed the tube formation of cardiac
      microvascular endothelial cells. CpG-ODN preconditioning significantly protects
      cardiac function against MI by suppressing the energy metabolism of
      cardiomyocytes and promoting angiogenesis. Our data also indicate that CpG-ODN
      preconditioning may be useful in MI therapy.

PMID- 29057538
TI  - Enhanced gastric cancer growth potential of mesenchymal stem cells derived from
      gastric cancer tissues educated by CD4+ T cells.
AB  - OBJECTIVES: Gastric cancer mesenchymal stem cells (GC-MSCs) can promote the
      development of tumour growth. The tumour-promoting role of tumour-associated MSCs
      and T cells has been demonstrated. T cells as the major immune cells may
      influence and induce a pro-tumour phenotype in MSCs. This study focused on
      whether CD4+ T cells can affect GC-MSCs to promote gastric cancer growth.
      MATERIALS AND METHODS: CD4+ T cells upregulation of programmed death ligand 1 (PD
      L1) expression in GC-MSCs through the phosphorylated signal transducer and
      activator of transcription (p-STAT3) signalling pathway was confirmed by
      immunofluorescence, western blotting and RT-PCR. Migration of GC cells was
      detected by Transwell migration assay, and apoptosis of GC cells was measured by
      flow cytometry using annexin V/propidium iodide double staining. CD4+ T cell
      primed GC-MSCs promoted GC growth in a subcutaneously transplanted tumour model
      in BALB/c nu/nu mice. RESULTS: Gastric cancer mesenchymal stem cells stimulated
      by activated CD4+ T cells promoted migration of GC cells and enhanced GC growth
      potential in BALB/c nu/nu xenografts. PD-L1 upregulation of GC-MSCs stimulated by
      CD4+ T cells was mediated through the p-STAT3 signalling pathway. CD4+ T cells
      primed GC-MSCs have greater GC volume and growth rate-promoting role than GC
      MSCs, with cancer cell-intrinsic PD-1/mammalian target of rapamycin (mTOR)
      signalling activation. CONCLUSIONS: This study showed that GC-MSCs are plastic.
      The immunophenotype of GC-MSCs stimulated by CD4+ T cells has major changes that
      may influence tumour cell growth. This research was based on the interaction
      between tumour cells, MSCs and immune cells, providing a new understanding of the
      development and immunotherapy of GC.

PMID- 29057539
TI  - Comparative safety of systemic and low-bioavailability steroids in inflammatory
      bowel disease: Systematic review and network meta-analysis.
AB  - AIMS: Oral systemic corticosteroids have been used to induce remission in
      patients with active inflammatory bowel disease (IBD) for over 50 years; however,
      the wide array of adverse events (AEs) associated with these drugs prompted the
      development of steroid compounds with targeted delivery and low systemic
      bioavailability. This study assessed corticosteroids' comparative harm using
      network meta-analysis. METHODS: We searched PubMed, Scopus, Embase, the Cochrane
      Library, clinical trial registries, regulatory authorities' websites and major
      conference proceedings, through March 2017. Randomized controlled trials that
      recruited adult IBD patients and compared oral systemic corticosteroids
      (prednisone/prednisolone) or compounds/formulations with low systemic
      bioavailability (budesonide, budesonide MMX, and beclomethasone dipropionate)
      with placebo, or against each other, were considered eligible for inclusion. Two
      reviewers independently extracted study data and outcomes, and rated each trial's
      risk-of-bias. RESULTS: We identified and synthesized evidence from 31 trials
      including 5689 IBD patients. Budesonide MMX was associated with significantly
      fewer corticosteroid-related AEs than oral systemic corticosteroids [odds ratio
      (OR): 0.25, 95% confidence interval (CI): 0.13-0.49] and beclomethasone (OR:
      0.35, 95% CI: 0.13-1.00), but not significantly fewer AEs than budesonide (OR:
      0.64, 95% CI: 0.37-1.11); it performed equally good with placebo. By contrast,
      the occurrence of serious AEs, and treatment discontinuations due to AEs, did not
      differ between the comparator treatments. CONCLUSIONS: Budesonide MMX is
      associated with fewer corticosteroid-related AEs than its comparator steroid
      treatments for adult IBD patients. Further high-quality research is warranted to
      illuminate the steroid drugs' comparative safety profiles.

PMID- 29057541
TI  - Transplantation of adipose tissue-derived stem cell-derived exosomes ameliorates
      erectile function in diabetic rats.
AB  - Mesenchymal stem cells (MSCs) have been considered as an attractive tool for the
      therapy of diseases. Accumulating evidence indicates that the healing effects of
      MSCs are mainly related to paracrine action rather than transdifferentiation.
      Exosomes excreted from MSCs have emerged as physiologically relevant and powerful
      components of the MSC secretome. However, whether MSC-derived exosomes can
      improve erectile function of streptozotocin-induced diabetic rats and its
      mechanism remains unknown. Our previous work showed that adipose tissue-derived
      stem cells (ADSCs) transplantation could increase endothelial and smooth muscle
      contents and improve erectile function of diabetic rats. In this study, ADSC
      derived exosomes (ADSC-Exo) exhibited in vitro proangiogenic properties, induced
      the proliferation of endothelial cells and restored erectile function in vivo, as
      well as decreased fibrosis of corpus cavernosum. In further experiments, we found
      that ADSC-Exo contained some proangiogenic (miR-126, miR-130a and miR-132)
      microRNAs and an antifibrotic microRNA family (miR-let7b and miR-let7c). Thus, it
      is reasonable to postulate that ADSC-Exo transports key functional miRNAs to
      target cells in a specific manner to improve functional recovery or to activate
      endogenous repair mechanisms. This proof-of-concept study provides a novel
      approach for the treatment of diabetic erectile dysfunction.

PMID- 29057542
TI  - Sleep DownUnder 2017, 29th ASM of Australasian Sleep Association and the
      Australasian Sleep Technologists Association, 25-28 October 2017, Auckland, New
      Zealand.

PMID- 29057540
TI  - Differential actions of AMP kinase on ATP-sensitive K+ currents in ventral
      tegmental area and substantia nigra zona compacta neurons.
AB  - ATP-sensitive K+ (K-ATP) channels play significant roles in regulating the
      excitability of dopamine neurons in the substantia nigra zona compacta (SNC). We
      showed previously that K-ATP channel function is up-regulated by AMP-activated
      protein kinase (AMPK). This study extended these studies to the neurons adjacent
      to the SNC in the ventral tegmental area (VTA). Using patch pipettes to record
      whole-cell currents in slices of rat midbrain, we found that the AMPK activator
      A769662 increased the amplitude of currents evoked by the K-ATP channel opener
      diazoxide in presumed dopamine-containing VTA neurons. However, current evoked by
      diazoxide with A769662 was significantly smaller in VTA neurons compared to SNC
      neurons. Moreover, a significantly lower proportion of VTA neurons responded to
      diazoxide with outward current. However, A769662 was able to increase the
      incidence of diazoxide-responsive neurons in the VTA. In contrast, A769662 did
      not potentiate diazoxide-evoked currents in presumed non-dopamine VTA neurons.
      These results show that AMPK activation augments K-ATP currents in presumed
      dopamine neurons in the VTA and SNC, although diazoxide-evoked currents remain
      less robust in the VTA. We conclude that K-ATP channels may play important
      physiological roles in VTA and SNC dopamine neurons.

PMID- 29057544
TI  - AFAP1-AS1: A novel oncogenic long non-coding RNA in human cancers.
AB  - Long non-coding RNAs (lncRNAs), a group of non-protein-coding RNAs with more than
      200 nucleotides in length, are involved in multiple biological processes, such as
      the proliferation, apoptosis, migration and invasion. Moreover, numerous studies
      have shown that lncRNAs play important roles as oncogenes or tumour suppressor
      genes in human cancers. In this paper, we concentrate on actin filament
      associated protein 1-antisense RNA 1 (AFAP1-AS1), a well-known long non-coding
      RNA that is overexpressed in various tumour tissues and cell lines, including
      oesophageal cancer, pancreatic ductal adenocarcinoma, nasopharyngeal carcinoma,
      lung cancer, hepatocellular carcinoma, ovarian cancer, colorectal cancer, biliary
      tract cancer and gastric cancer. Moreover, high expression of AFAP1-AS1 was
      associated with the clinicopathological features and cancer progression. In this
      review, we sum up the current studies on the characteristics of AFAP1-AS1 in the
      biological function and mechanism of human cancers.

PMID- 29057543
TI  - Cortical responses before 6 months of life associate with later autism.
AB  - Autism spectrum disorder (ASD) is a common, highly heritable, developmental
      disorder and later-born siblings of diagnosed children are at higher risk of
      developing ASD than the general population. Although the emergence of behavioural
      symptoms of ASD in toddlerhood is well characterized, far less is known about
      development during the first months of life of infants at familial risk. In a
      prospective longitudinal study of infants at familial risk followed to 36 months,
      we measured functional near-infrared spectroscopy (fNIRS) brain responses to
      social videos of people (i.e. peek-a-boo) compared to non-social images
      (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months,
      infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced
      activation to visual social stimuli relative to low-risk infants (N = 16) across
      inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex.
      Furthermore, these infants also showed reduced activation to vocal sounds and
      enhanced activation to non-vocal sounds within left lateralized temporal (aMTG
      STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who
      did not develop ASD (N = 15). The degree of activation to both the visual and
      auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood.
      These preliminary findings are consistent with later atypical social brain
      responses seen in children and adults with ASD, and highlight the need for
      further work interrogating atypical processing in early infancy and how it may
      relate to later social interaction and communication difficulties characteristic
      of ASD.

PMID- 29057545
TI  - Modelling incremental benefits on complications rates when targeting lower HbA1c
      levels in people with Type 2 diabetes and cardiovascular disease.
AB  - AIM: Glucose-lowering interventions in Type 2 diabetes mellitus have demonstrated
      reductions in microvascular complications and modest reductions in macrovascular
      complications. However, the degree to which targeting different HbA1c reductions
      might reduce risk is unclear. METHODS: Participant-level data for Trial
      Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with
      established cardiovascular disease were used in a Type 2 diabetes-specific
      simulation model to quantify the likely impact of different HbA1c decrements on
      complication rates. Ten-year micro- and macrovascular rates were estimated with
      HbA1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%)
      while holding other risk factors constant at their baseline levels. Cumulative
      relative risk reductions for each outcome were derived for each HbA1c decrement.
      RESULTS: Of 5717 participants studied, 72.0% were men and 74.2% White European,
      with a mean (sd) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9)
      mmHg, LDL-cholesterol 2.3 (0.9) mmol/l, HDL-cholesterol 1.13 (0.3) mmol/l and
      median Type 2 diabetes duration 9.6 (5.1-15.6) years. Ten-year cumulative
      relative risk reductions for modelled HbA1c values of 75, 64, 53 and 42 mmol/mol,
      relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial
      infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and
      46.4% for diabetes-related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation;
      and 13.6%, 25.4%, 36.0% and 44.7 for single-eye blindness. CONCLUSIONS: These
      simulated complication rates might help inform the degree to which complications
      might be reduced by targeting particular HbA1c reductions in Type 2 diabetes.

PMID- 29057546
TI  - Clinical features and biological implications of different U2AF1 mutation types
      in myelodysplastic syndromes.
AB  - U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS)
      without ring sideroblasts. The aim of this study was to investigate the clinical
      and biological implications of different U2AF1 mutation types in MDS. We
      performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty-six
      patients (17%) were found to have U2AF1MT, which occurred more common in younger
      patients (P = .001) and represented ancestral lesions in a substantial proportion
      (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT
      positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely
      associated with U2AF1MT. U2AFS34 subjects were enriched for isolated +8 and were
      inversely associated with complex karyotypes. U2AF1MT was significantly
      associated with anemia, thrombocytopenia, and poor survival in both lower-risk
      and higher-risk MDS. U2AF1S34 subjects had more frequently platelet levels of <50
      * 109 /L (P = .043) and U2AF1Q157 /U2AF1R156 subjects had more frequently
      hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P
      = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest
      genetic events in MDS patients and that different types of U2AF1MT have distinct
      clinical and biological characteristics.

PMID- 29057547
TI  - Knockdown of long non-coding RNA ANRIL inhibits proliferation, migration, and
      invasion but promotes apoptosis of human glioma cells by upregulation of miR-34a.
AB  - Gliomas are the most common types of primary central nervous system malignancy
      found in adults. Long non-coding RNA antisense non-coding RNA in the INK4 locus
      (ANRIL) variants are associated with glioma and miR-34a is markedly downregulated
      in U251 glioma cells. The 3'-untranslated region (3'UTR) of silent information
      regulator 1 (Sirt1) contains a conserved site that is targeted directly by miR
      34a. Therefore, in this study, we investigated the roles of ANRIL, miR-34a, and
      Sirt1 in glioma and their potential interactions. Firstly, expression of ANRIL in
      normal glia cells and five glioma cell lines was measured. Then, effects of ANRIL
      suppression on cell proliferation, apoptosis, migration and invasion of U251
      cells as well as expression of miR-34a were assessed. Meanwhile, effects of miR
      34a on U251 cells silencing ANRIL were tested. Whether Sirt1 is a target of miR
      34a was verified, followed by estimating the role of Sirt1 overexpression in U251
      cells overexpressing miR-34a. Finally, the involved signaling pathways were
      assessed. ANRIL was upregulated in glioma cells and its suppression inhibited
      cell proliferation, migration and invasion but promoted cell apoptosis. ANRIL
      acted as a sponge of miR-34a, and Sirt1 is a target of miR-34a. Then, Sirt1 was
      proved to function through activation of the PI3K/AKT and mTOR signaling
      pathways. In conclusion, ANRIL was upregulated in glioma, and its inhibition
      could repress cell proliferation, migration and invasion but inhibit cell
      apoptosis through miR-34a-mediated downregulation of Sirt1, involving the
      inactivation of the PI3K/AKT and mTOR pathways.

PMID- 29057548
TI  - Nurses and nurse assistants' experiences with using a design thinking approach to
      innovation in a nursing home.
AB  - AIM: The aim of this study was to evaluate nurses' and nurse assistants'
      experiences with a design thinking approach to innovation used in a nursing home
      in Norway. BACKGROUND: A design thinking approach to innovation that focuses on
      users' needs can be employed to address many of the challenges facing health care
      providers in a field facing a growing ageing population, complex diseases and
      financial shortfalls. EVALUATION: This study is based on a thematic analysis of
      four focus group interviews with nurses and nurse assistants (n = 23). KEY
      ISSUES: In the initial phase of developing the new service model, which included
      defining staff roles and responsibilities, participating nurses and nurse
      assistants felt engaged and motivated by the designers' inclusive and creative
      methods. However, during the new model's testing phase, they were critical of
      management's lack of involvement in the model's implementation and therefore
      became less motivated about the project. CONCLUSION: The findings of the study
      highlight the importance of the designers cooperating with management and staff
      for the duration of the innovation process. IMPLICATIONS FOR NURSING MANAGEMENT:
      Challenging innovation processes require strong managers who engage with
      designers, patients, staff and volunteers throughout all phases of an innovation
      process using a design thinking approach.

PMID- 29057549
TI  - Flooding: what is the impact on pregnancy and child health?
AB  - Floods are the most common type of natural disaster in both developed and
      developing countries and have led to extensive morbidity and mortality throughout
      the world. Worldwide, over the past 30 years, flooding has claimed the lives of
      more than 200,000 people and affected more than 2.8 billion others. The impact of
      flooding on health varies among populations and depends primarily on
      vulnerability and the kind of event experienced. It severely disrupts livelihoods
      and has a significant impact on the health of pregnant women and children. In
      addition, it may exacerbate a range of negative psychological and physiological
      child and reproductive health outcomes. Awareness-raising, education, and the
      issuing of warnings appear to be key initiatives to mitigate or prevent flood
      morbidity and mortality, especially among people living in low- and middle-income
      countries. Agencies responding to emergencies also need to be more cognisant of
      the dangers, specifically those engaged in healthcare, nutrition, and water
      safety programmes.

PMID- 29057550
TI  - In Vitro Magnetic Resonance Imaging Evaluation of Fragmented, Open-Coil,
      Percutaneous Peripheral Nerve Stimulation Leads.
AB  - OBJECTIVE: Percutaneous peripheral nerve stimulation (PNS) is an FDA-cleared pain
      treatment. Occasionally, fragments of the lead (MicroLead, SPR Therapeutics, LLC,
      Cleveland, OH, USA) may be retained following lead removal. Since the lead is
      metallic, there are associated magnetic resonance imaging (MRI) risks. Therefore,
      the objective of this investigation was to evaluate MRI-related issues (i.e.,
      magnetic field interactions, heating, and artifacts) for various lead fragments.
      METHODS: Testing was conducted using standardized techniques on lead fragments of
      different lengths (i.e., 50, 75, and 100% of maximum possible fragment length of
      12.7 cm) to determine MRI-related problems. Magnetic field interactions (i.e.,
      translational attraction and torque) and artifacts were tested for the longest
      lead fragment at 3 Tesla. MRI-related heating was evaluated at 1.5 Tesla/64 MHz
      and 3 Tesla/128 MHz with each lead fragment placed in a gelled-saline filled
      phantom. Temperatures were recorded on the lead fragments while using relatively
      high RF power levels. Artifacts were evaluated using T1-weighted, spin echo, and
      gradient echo (GRE) pulse sequences. RESULTS: The longest lead fragment produced
      only minor magnetic field interactions. For the lead fragments evaluated,
      physiologically inconsequential MRI-related heating occurred at 1.5 Tesla/64 MHz
      while under certain 3 Tesla/128 MHz conditions, excessive temperature elevations
      may occur. Artifacts extended approximately 7 mm from the lead fragment on the
      GRE pulse sequence, suggesting that anatomy located at a position greater than
      this distance may be visualized on MRI. CONCLUSIONS: MRI may be performed safely
      in patients with retained lead fragments at 1.5 Tesla using the specific
      conditions of this study (i.e., MR Conditional). Due to possible excessive
      temperature rises at 3 Tesla, performing MRI at that field strength is currently
      inadvisable.

PMID- 29057551
TI  - To do or not to do kidney biopsy in pediatric donors to evaluate transplant
      eligibility?

PMID- 29057552
TI  - Children prenatally exposed to maternal anxiety devote more attentional resources
      to neutral pictures.
AB  - Maternal anxiety during pregnancy can negatively affect fetal neurodevelopment,
      predisposing the offspring to a higher risk of behavioral and emotional problems
      later in life. The current study investigates the association between maternal
      anxiety during pregnancy and child affective picture processing using event
      related brain potentials (ERPs). Mothers reported anxiety during the second
      trimester using the anxiety subscale of the Symptom Checklist (SCL-90). At age 4
      years, child affective picture processing (N = 86) was measured by recording ERPs
      during viewing of neutral, pleasant, and unpleasant pictures selected from the
      International Affective Pictures System. The late positive potential (LPP)-an ERP
      component reflecting individual differences in affective processing-was used as
      child outcome. The expected positive association between maternal anxiety and LPP
      amplitude for unpleasant pictures was not found. Nevertheless, we found a
      positive association between maternal anxiety during pregnancy and LPP amplitudes
      for neutral pictures in the middle and late time window at anterior locations
      (all p < .05). These associations remained significant after adjusting for
      maternal postnatal anxiety and gestational age at birth and after FDR correction
      for multiple comparisons. Our study provides neurophysiological evidence that
      children prenatally exposed to higher maternal anxiety devote more attentional
      resources to neutral pictures, but not to unpleasant pictures. Possibly, these
      children show enhanced vigilance for threat when viewing neutral pictures.
      Although useful in dangerous environments, this enhanced vigilance may predispose
      children prenatally exposed to higher maternal anxiety to developing behavioral
      and/or emotional problems later in life. A video abstract of this article can be
      viewed at: https://www.youtube.com/watch?v=kEzYi6IS2HA.

PMID- 29057553
TI  - Thickness and morphology assessment of nail polishes applied on nails by high
      definition optical coherence tomography.

PMID- 29057554
TI  - Biodiversity and ecosystem functioning in food webs: the vertical diversity
      hypothesis.
AB  - One challenge in merging community and ecosystem ecology is to integrate the
      complexity of natural multitrophic communities into concepts of ecosystem
      functioning. Here, we combine food-web and allometry theories to demonstrate that
      primary production, as measured by the total nutrient uptake of the multitrophic
      community, is determined by vertical diversity (i.e. food web's maximum trophic
      level) and structure (i.e. distributions of species and their abundances and
      metabolic rates across trophic levels). In natural ecosystems, the community size
      distribution determines all these vertical patterns and thus the total nutrient
      uptake. Our model suggests a vertical diversity hypothesis (VDH) for ecosystem
      functioning in complex food webs. It predicts that, under a given nutrient
      supply, the total nutrient uptake increases exponentially with the maximum
      trophic level in the food web and it increases with its maximum body size
      according to a power law. The VDH highlights the effect of top-down regulation on
      plant nutrient uptake, which complements traditional paradigms that emphasised
      the bottom-up effect of nutrient supply on vertical diversity. We conclude that
      the VDH contributes to a synthetic framework for understanding the relationship
      between vertical diversity and ecosystem functioning in food webs and predicting
      the impacts of global changes on multitrophic ecosystems.

PMID- 29057556
TI  - Tumor-derived exosomes enhance invasion and metastasis of salivary adenoid cystic
      carcinoma cells.
AB  - OBJECTIVES: Tumor-derived exosomes (TDE) have been shown to participate in
      different steps of the dissemination of cancer cells. However, the role of
      salivary adenoid cystic carcinoma-derived (SACC-derived) exosomes had not been
      documented in SACC. The study aims to explore the functions of SACC-derived TDE
      in SACC progression and investigate potential mechanisms. METHODS: Salivary
      adenoid cystic carcinoma cell line SACC-83 was used to generate TDE. Afterward,
      SACC-83 or HUVECs were cocultured with or without TDE. Tumor migration, tumor
      invasion, and endothelial permeability were examined by wound healing assay,
      tumor invasion assay, endothelial permeability assay, and tumor cell
      transendothelial migration assay, respectively. Moreover, the expression levels
      of cell junction-related proteins were examined by qRT-PCR and Western blot.
      RESULTS: Salivary adenoid cystic carcinoma -83-derived exosomes were taken up by
      their host cells. Meanwhile, TDE increased migration and invasion capacity of
      SACC-83 cells and enhanced endothelial cell permeability. Furthermore, we
      demonstrated that the expression of cell junction-related proteins (Claudins and
      ZO-1) was downregulated, which is presumably involved in the TDE-mediated
      promotion of migration, invasion, and metastasis. CONCLUSION: The results
      suggested that SACC cell-derived exosomes were loaded with individual components
      that could enhance invasiveness and induce microenvironment changes, thus
      promoting SACC aggression.

PMID- 29057555
TI  - The cost of simplifying complex developmental phenomena: a new perspective on
      learning to walk.
AB  - Researchers can study complex developmental phenomena with all the inherent noise
      and complexity or simplify behaviors to hone in on the essential aspects of a
      phenomenon. We used the development of walking as a model system to compare the
      costs and benefits of simplifying a complex, noisy behavior. Traditionally,
      researchers simplify infant walking by recording gait measures as infants take
      continuous, forward steps along straight paths. Here, we compared the traditional
      straight-path task with spontaneous walking during 20 minutes of free play in 97
      infants (10.75-19.99 months of age). We recorded infants' footfalls on an
      instrumented floor to calculate gait measures in the straight-path and free-play
      tasks. In addition, we scored videos for other critical aspects of spontaneous
      walking-steps per bout, shape of walking path, and step direction. Studying
      infant walking during free play incurred no cost compared with the straight-path
      task, but considerable benefits. Straight-path gait was highly correlated with
      spontaneous gait and both sets of measures improved with walking age, validating
      use of the straight-path task as an index of development. However, a large
      proportion of free-play bouts were too short to permit standard gait measures,
      and most bouts were curved with omnidirectional steps. The high prevalence of
      these "non-canonical" bouts was constant over development. We propose that a
      focus on spontaneous walking, the phenomenon we ostensibly wish to explain,
      yields important insights into the problems infants solve while learning to walk.
      Other areas of developmental research may also benefit from retaining the
      complexity of complex phenomena.

PMID- 29057557
TI  - Valence-Engineering of Quantum Dots Using Programmable DNA Scaffolds.
AB  - Precise control over the valency of quantum dots (QDs) is critical and
      fundamental for quantitative imaging in living cells. However, prior approaches
      on valence control of QDs remain restricted to single types of valences. A DNA
      programmed general strategy is presented for valence engineering of QDs with high
      modularity and high yield. By employing a series of programmable DNA scaffolds,
      QDs were generated with tunable valences in a single step with near-quantitative
      yield (>95 %). The use of these valence-engineered QDs was further demonstrated
      to develop 12 types of topologically organized QDs-QDs and QDs-AuNPs and 4 types
      of fluorescent resonance energy transfer (FRET) nanostructures. Quantitative
      analysis of the FRET nanostructures and live-cell imaging reveal the high
      potential of these nanoprobes in bioimaging and nanophotonic applications.

PMID- 29057558
TI  - Editorial Comment to Influence of dutasteride treatment on serum hormone levels
      and aging male symptoms in patients with benign prostatic enlargement.

PMID- 29057559
TI  - A Magneto-optical Molecular Device: Interplay of Spin Crossover, Luminescence,
      Photomagnetism, and Photochromism.
AB  - A bis(pyrazolylpyridyl) ligand, L, containing a central photochromic
      dithienylethene spacer predictably forms a ferrous [Fe2 L3 ]4+ helicate
      exhibiting spin crossover (SCO). In solution, the compound [Fe2 L3 ](ClO4 )4 (1)
      preserves the magnetic properties and is fluorescent. The structure of 1 is photo
      switchable following the reversible ring closure/opening of the central
      dithienylethene via irradiation with UV/visible light. This photoisomerization
      switches on and off some emission bands of 1 and provides a means of externally
      manipulating the magnetic properties of the assembly.

PMID- 29057560
TI  - The first titin (c.59926 + 1G > A) founder mutation associated with dilated
      cardiomyopathy.

PMID- 29057563
TI  - Models versus theories as a primary carrier of nursing knowledge: A philosophical
      argument.
AB  - Theories and models are not equivalent. I argue that an orientation towards
      models as a primary carrier of nursing knowledge overcomes many ongoing
      challenges in philosophy of nursing science, including the theory-practice divide
      and the paradoxical pursuit of predictive theories in a discipline that is
      defined by process and a commitment to the non-reducibility of the health/care
      experience. Scientific models describe and explain the dynamics of specific
      phenomenon. This is distinct from theory, which is traditionally defined as
      propositions that explain and/or predict the world. The philosophical case has
      been made against theoretical universalism, showing that a theory can be true in
      its domain, but that no domain is universal. Subsequently, philosophers focused
      on scientific models argued that they do the work of defining the boundary
      conditions-the domain(s)-of a theory. Further analysis has shown the ways models
      can be constructed and function independent of theory, meaning models can
      comprise distinct, autonomous "carriers of scientific knowledge." Models are
      viewed as representations of the active dynamics, or mechanisms, of a phenomenon.
      Mechanisms are entities and activities organized such that they are productive of
      regular changes. Importantly, mechanisms are by definition not static: change may
      alter the mechanism and thereby alter or create entirely new phenomena. Orienting
      away from theory, and towards models, focuses scholarly activity on dynamics and
      change. This makes models arguably critical to nursing science, enabling the
      production of actionable knowledge about the dynamics of process and change in
      health/care. I briefly explore the implications for nursing-and health/care
      knowledge and practice.

PMID- 29057561
TI  - Pre-clinical results in pig-to-non-human primate islet xenotransplantation using
      anti-CD40 antibody (2C10R4)-based immunosuppression.
AB  - BACKGROUND: Islet transplantation is an effective therapy for selected patients
      with type 1 diabetes with labile glycemic control and hypoglycemic unawareness,
      but donor organs are limited. Islet xenotransplantation using porcine islets will
      potentially solve this problem. Although successful proof of concept studies
      using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non
      human primate (NHP) islet xenotransplantation has been demonstrated by several
      groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based
      studies have not been reported. METHODS: Nine streptozotocin (STZ)-induced
      diabetic rhesus monkeys were transplanted with adult porcine islets isolated from
      designated pathogen-free (DPF) miniature pigs. They were treated with anti-CD40
      mAb-based immunosuppressive regimen and were divided into 3 groups: anti-CD40
      only group (n = 2), belatacept group (anti-CD40 mAb+belatacept, n = 2), and
      tacrolimus group (anti-CD40 mAb+tacrolimus, n = 5). All monkeys received anti
      thymocyte globulin (ATG), cobra venom factor (CVF), adalimumab, and sirolimus.
      Blood glucose levels (BGL) and serum porcine C-peptide concentrations were
      measured. Humoral and cellular immune responses were assessed by ELISA and
      ELISPOT, respectively. Liver biopsy and subsequent immunohistochemistry were
      conducted. RESULTS: All animals restored normoglycemia immediately after porcine
      islet transplantation and finished the follow-up without any severe adverse
      effects except for one animal (R092). Most animals maintained their body weight.
      Median survival, as defined by a serum porcine C-peptide concentration of >0.15
      ng/mL, was 31, 27, and 60 days for anti-CD40 only, belatacept, and tacrolimus
      groups, respectively. Anti-alphaGal IgG levels in serum and the number of
      interferon-gamma secreting T cells in peripheral blood mononuclear cells did not
      increase in most animals. CONCLUSION: These results showed that anti-CD40 mAb
      combined with tacrolimus was effective in prolonging porcine islet graft
      survival, but anti-CD40 mAb was not as effective as anti-CD154 mAb in terms of
      preventing early islet loss.

PMID- 29057562
TI  - Complications of the neovagina in male-to-female transgender surgery: A
      systematic review and meta-analysis with discussion of management.
AB  - Gender-affirmation surgery is often the final gender-confirming medical
      intervention sought by those patients suffering from gender dysphoria. In the
      male-to-female (MtF) transgendered patient, the creation of esthetic and
      functional external female genitalia with a functional vaginal channel is of the
      utmost importance. The aim of this review and meta-analysis is to evaluate the
      epidemiology, presentation, management, and outcomes of neovaginal complications
      in the MtF transgender reassignment surgery patients. PUBMED was searched in
      accordance with PRISMA guidelines for relevant articles (n = 125). Ineligible
      articles were excluded and articles meeting all inclusion criteria went on to
      review and analysis (n = 13). Ultimately, studies reported on 1,684 patients with
      an overall complication rate of 32.5% and a reoperation rate of 21.7% for non
      esthetic reasons. The most common complication was stenosis of the neo-meatus
      (14.4%). Wound infection was associated with an increased risk of all tissue
      healing complications. Use of sacrospinous ligament fixation (SSL) was associated
      with a significantly decreased risk of prolapse of the neovagina. Gender
      affirmation surgery is important in the treatment of gender dysphoric patients,
      but there is a high complication rate in the reported literature. Variability in
      technique and complication reporting standards makes it difficult to assess the
      accurately the current state of MtF gender reassignment surgery. Further research
      and implementation of standards is necessary to improve patient outcomes. Clin.
      Anat. 31:191-199, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29057564
TI  - Effect of fetal hemodynamics on growth in fetuses with single ventricle or
      transposition of the great arteries.
AB  - OBJECTIVES: As birth weight is a critical predictor of outcome in neonates with
      congenital heart defect (CHD), the common problem of poor fetal growth in this
      population is clinically important. However, it is not well understood and the
      impact of fetal hemodynamics on fetal growth and birth weight in those with CHD
      has not been assessed. In this study, we sought to evaluate the association
      between combined cardiac output (CCO) and fetal middle cerebral artery (MCA) and
      umbilical artery (UA) pulsatility indices (PIs) and fetal growth in different
      subgroups of CHD, and to study the effects of fetal hemodynamics on late
      gestational weight gain. We hypothesized that fetuses with CHD will have lower
      CCO and be smaller at birth. METHODS: This was a retrospective review of fetal
      echocardiograms from 67 fetuses diagnosed with hypoplastic left heart syndrome
      (HLHS, n = 30), non-HLHS single ventricle (SV) (n = 20) or dextrotransposition of
      the great arteries (d-TGA, n = 17), compared with normal controls (n = 42). CCO
      was calculated using valvar area, velocity-time integral and heart rate and
      indexed to estimated fetal weight. MCA- and UA-PI were calculated using systolic,
      diastolic and mean velocities. Fetal biometry was recorded. Regression models
      were used to study trends in CCO, MCA- and UA-PI and fetal biometry over
      gestational age. To evaluate fetal weight gain in late gestation, Z-scores of
      estimated fetal weight at 30 weeks and birth weight were compared. Regression
      analysis was used to determine the associations of CCO, indexed CCO and MCA- and
      UA-PI at 30 weeks with birth weight, length and head circumference Z-scores, in
      addition to weight gain late in gestation. The gestational age of 30 weeks was
      chosen based on previous studies that found evidence of poor weight gain in
      fetuses with CHD in late gestation, starting at around that time. RESULTS: CCO
      increased with gestation in all four groups but the rate was slower in fetuses
      with HLHS and in those with SV. MCA-PI was lower in fetuses with HLHS compared
      with in those with non-HLHS-SV throughout gestation, suggesting different
      cerebral blood distribution. At the end of gestation, rate of fetal weight gain
      slowed in those with HLHS and in those with SV (similar to CCO curves), and head
      circumference growth rate slowed in all groups but controls. CCO, indexed CCO and
      MCA- and UA-PI did not correlate with any of the birth measurements or with
      weight gain late in gestation in fetuses with CHD. CONCLUSIONS: We found no
      associations of CCO or MCA- and UA-PI with late gestational weight gain or
      biometry at birth in fetuses with CHD. This does not support fetal hemodynamics
      as the primary driver of suboptimal fetal growth in fetuses with SV. Future
      research could further explain genetic and placental abnormalities that may
      affect fetal growth in those with CHD. Copyright (c) 2017 ISUOG. Published by
      John Wiley & Sons Ltd.

PMID- 29057565
TI  - Spectrophotometer is useful for assessing vitiligo and chemical leukoderma
      severity by quantifying color difference with surrounding normally pigmented
      skin.
AB  - BACKGROUND: Acquired skin hypopigmentation has many etiologies, including
      autoimmune melanocyte destruction, skin aging, inflammation, and chemical
      exposure. Distinguishing lesions from normally pigmented skin is clinically
      important to precisely assess disease severity. However, no gold standard
      assessment method has been reported. We aimed to investigate whether
      spectrophotometers are useful for assessing vitiligo and rhododendrol (4-(4
      hydroxyphenol)-2-butanol) (Rhododenol(r) )-induced leukoderma disease severity by
      quantifying skin color. METHODS: Mexameter(r) MX18 and CM-700d spectrophotometer
      were used for assessing vitiligo/leukoderma by measuring melanin index, L*a*b*
      color space, and DeltaE*ab value, which represents the color difference between
      two subjects and is calculated by the values of L*a*b*. RESULTS: MX18 and CM-700d
      can quantitatively distinguish vitiligo/leukoderma from normally pigmented skin
      based on melanin index. CM-700d consistently quantified the color of
      vitiligo/leukoderma lesions and surrounding normally pigmented skin in L*a*b*
      color spaces and DeltaE*ab. DeltaE*ab is well correlated with melanin index and
      clinical appearance. CONCLUSION: DeltaE*ab has been frequently used in aesthetic
      dentistry; however, current study is the first to use it in the measurement of
      skin color. DeltaE*ab seems to be a useful parameter to evaluate the color
      contrast between vitiligo/leukoderma and surrounding normally pigmented skin and
      can be used to evaluate disease severity and patient's quality of life.

PMID- 29057567
TI  - Q-switched Nd: YAG laser alone or with modified Jessner chemical peeling for
      treatment of mixed melasma in dark skin types: A comparative clinical,
      histopathological, and immunohistochemical study.
AB  - BACKGROUNDS: Treatment of mixed melasma remains challenging. Promising results
      have been achieved with low-fluence 1064-nm Q-switched Nd-YAG laser; however,
      multiple sessions are necessary with occurrence of complications especially in
      dark skin types. So, combination methods may be recommended. AIMS: To compare
      efficacy of Q-switched Nd-YAG laser alone or with modified Jessner's peel in
      mixed melasma in dark skin. PATIENTS/METHODS: Nineteen patients with mixed
      melasma received 6 sessions of laser on left side of face and alternating laser
      and modified Jessner on right side. Evaluation was carried out clinically through
      modified melasma area and severity index at 1 month after last session. Using
      histopathological, immunohistochemical, and computerized morphometric analysis,
      objective evaluation of melanin particle surface area and MART-1-positive cells
      was performed for pre- and post-treated skin biopsies. RESULTS: There was
      significant clinical improvement on both sides of face (P < .001), without
      significant difference (P > .05). At the sixth laser session on left side of
      face, ill-defined mottled hypopigmentation was observed in 21.05% of patients.
      Histopathologically, melanin particle surface area and number of MART-1-positive
      cells (total, epidermal, and dermal) were significantly decreased after two
      treatment modalities (P < .001), without significant difference in their
      reduction percentage between both sides of face (P > .05). CONCLUSION: Low
      fluence Q-switched Nd-YAG laser alone and with modified Jessner's peel are
      equally effective regimens for mixed melasma clinically, histopathologically, and
      immunohistochemically. However, combined method is preferred, especially in dark
      skin, for obtaining better cosmetic result with fewer side effects of multiple
      laser sessions and decreasing cost rate of laser.

PMID- 29057566
TI  - Diminished socially selective neural processing in 5-month-old infants at high
      familial risk of autism.
AB  - The social and communicative difficulties that characterize autism spectrum
      disorder (ASD) are considered the most striking feature of the disorder. Research
      has reported that individuals with ASD show abnormalities in the brain regions
      associated with the processing of social information. Importantly, a recent study
      using functional near-infrared spectroscopy (fNIRS) found the first evidence of
      atypicalities in the neural processing of social information in 4- to 6-month-old
      infants at high familial risk of ASD. These findings provide an important step in
      the search for early markers of ASD and highlight the potential for neuroimaging
      techniques to detect atypical patterns of neural activity prior to the
      manifestation of most behavioural symptoms. This study aimed to extend the
      findings of reduced neural sensitivity to social stimuli in an independent
      cohort. Twenty-nine 5-month-old infants (13 low-risk infants, 16 high-risk
      infants) were presented with social and non-social visual stimuli, similar to the
      previous experiment. Importantly, a non-social dynamic motion control condition
      was introduced allowing the comparison between social dynamic and non-social,
      static, as well as dynamic stimuli. We found that while low-risk infants showed
      activation to social stimuli in the right posterior temporal cortex, this
      activation was reduced in infants at high risk of ASD. Although the current
      sample size was relatively small, our results replicate and extend previous work
      and provide evidence for a social processing difference in infants at risk of
      autism. Future research will determine whether these differences relate to an
      eventual ASD diagnosis or may rather reflect the broader autism phenotype.

PMID- 29057568
TI  - Atp1a3-deficient heterozygous mice show lower rank in the hierarchy and altered
      social behavior.
AB  - Atp1a3 is the Na-pump alpha3 subunit gene expressed mainly in neurons of the
      brain. Atp1a3-deficient heterozygous mice (Atp1a3+/- ) show altered
      neurotransmission and deficits of motor function after stress loading. To
      understand the function of Atp1a3 in a social hierarchy, we evaluated social
      behaviors (social interaction, aggression, social approach and social dominance)
      of Atp1a3+/- and compared the rank and hierarchy structure between Atp1a3+/- and
      wild-type mice within a housing cage using the round-robin tube test and
      barbering observations. Formation of a hierarchy decreases social conflict and
      promote social stability within the group. The hierarchical rank is a reflection
      of social dominance within a cage, which is heritable and can be regulated by
      specific genes in mice. Here we report: (1) The degree of social interaction but
      not aggression was lower in Atp1a3+/- than wild-type mice, and Atp1a3+/-
      approached Atp1a3+/- mice more frequently than wild type. (2) The frequency of
      barbering was lower in the Atp1a3+/- group than in the wild-type group, while no
      difference was observed in the mixed-genotype housing condition. (3) Hierarchy
      formation was not different between Atp1a3+/- and wild type. (4) Atp1a3+/- showed
      a lower rank in the mixed-genotype housing condition than that in the wild type,
      indicating that Atp1a3 regulates social dominance. In sum, Atp1a3+/- showed
      unique social behavior characteristics of lower social interaction and preference
      to approach the same genotype mice and a lower ranking in the hierarchy.

PMID- 29057569
TI  - The development of a core syllabus for the teaching of oral anatomy, histology,
      and embryology to dental students via an international 'Delphi Panel'.
AB  - The formulation of core syllabuses for the biomedical sciences within medical and
      dental courses is partially driven by the need to cope with decreased time
      allocations for these subjects as a result of major curricular changes taking
      place worldwide. There is also a requirement to deal with the request for
      increased clinical relevance. In response to such demands, the International
      Federation of Associations of Anatomists (IFAA) is devising core syllabuses for
      the anatomical sciences relating to the education and training of both scientific
      and clinical professions. The process initially involves using Delphi Panels
      consisting of a team of anatomists, scientists, and clinicians who evaluate
      syllabus content in detail and accord each element/topic 'essential,'
      'important,' 'acceptable,' or 'not required' status. Their conjectures, published
      on the IFAA website, provide merely a framework to enable other stakeholders to
      comment. The approach is international in scope, is conceptually 'democratic,'
      and is developmentally fluid in being readily available for amendment. The aim is
      to set internationally recognized standards and thus to provide guidelines
      concerning anatomical knowledge when engaged in course development. This article
      presents the deliberations of an IFAA Delphi Panel into a core syllabus for oral
      anatomy, histology, and embryology within the dental curriculum. Clin. Anat.
      31:231-249, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29057571
TI  - CyPA and Emmprin play a role in peri-implantitis.
AB  - BACKGROUND: Cyclophilin A (CyPA) and Emmprin play important roles in peri
      implantitis. However, their roles in the diagnosis and treatment of the disease
      are still unclear. PURPOSE: The aim of this split-mouth animal study was to
      describe variable trends of biomarkers during the progression of peri-implantitis
      and to define relationships among CyPA, Emmprin, and peri-implantitis. MATERIALS
      AND METHODS: Six male adult Labradors were used. The mandibular premolars and the
      first molar were extracted, and sixteen implants were placed after 3 months. Peri
      implantitis was induced around the implants on one side, which were the test
      group, and the implants on the other side were included in the control group.
      Clinical parameters such as probing depth, gingival index, and bleeding index and
      periapical X-rays were recorded at weeks 0, 2, 4, 6, 8, 10, and 12. Peri-implant
      crest fluid (PICF) and gingiva around the implants were collected and analyzed by
      ELISA and real-time PCR, respectively. RESULTS: The clinical parameters of the
      test group indicated severe inflammation around the implants. Radiographs showed
      obvious bone loss beginning at week 4, and it continued over time. The
      concentration of CyPA in the peri-implantitis group increased at first and then
      decreased beginning at week 6, and the concentration of Emmprin decreased at
      first and then increased beginning at week 6. Emmprin, matrix metalloproteinase-9
      and Tissue Inhibitor of Metalloproteinase-1 showed similar changes over time.
      CyPA showed a consistent trend with Interleukin-1beta, but showed an opposite
      trend to Transforming growth factor-beta. Both the concentration of CyPA in PICF
      and gene expression in gingival tissue increased before bone absorption occurred.
      CONCLUSION: Despite the limitations of this study, CyPA may be an early signal
      for peri-implantitis. A CyPA-Emmprin interaction exists in peri-implantitis and
      is Emmprin-dependent. Emmprin is related to clinical attachment loss in peri
      implantitis.

PMID- 29057570
TI  - Lanthanoid Pseudo-Grignard Reagents: A Major Untapped Resource.
AB  - Pseudo-Grignard reagents PhLnI (Ln=Yb, Eu), readily prepared by the oxidative
      addition of iodobenzene to ytterbium or europium metal at -78  degrees C in
      tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME), react with a range of bulky
      N,N'-bis(aryl)formamidines to generate an extensive series of LnII or more rarely
      LnIII complexes, namely [Eu(DippForm)I(thf)4 ]?thf (1), [{EuI2 (dme)2 }2 ] (2),
      [Eu(XylForm)I(dme)2 ]?0.5 dme (3 a), [Eu(XylForm)I(dme)(MU-dme)]n (3 b),
      [{Eu(XylForm)I(MU-OH)(thf)2 }2 ] (4), [Yb(DippForm)I(thf)3 ]?thf (5 a),
      [Yb(DippForm)I2 (thf)3 ]?2 thf (5 b), [{Yb(MesForm)I(thf)2 }2 ] (6),
      [{Yb(XylForm)I(thf)2 }2 ] (7 a), and [Yb(XylForm)2 I(dme)]?dme (7 b)
      {(Form=ArNCHNAr; XylForm (Ar=2,6-Me2 C6 H3 ), MesForm (Ar=2,4,6-Me3 C6 H2 ),
      DippForm (Ar=2,6-iPr2 C6 H3 )}. Reaction of PhEuI and MesFormH in DME
      consistently gave 2, and reaction with XylFormH in THF gave 4. Europium complexes
      1 and 3 a are seven-coordinate divalent monomers, whilst 3 b is a seven
      coordinate dme-bridged polymer. Complex 5 a of the smaller YbII is a six
      coordinate monomer, but the related 6 and 7 a are six-coordinate iodide-bridged
      dimers. 4 is a trivalent seven-coordinate hydroxide-bridged dimer, whereas
      complexes 5 b and 7 b are seven-coordinate monomeric YbIII derivatives. A
      characteristic structural feature is that iodide ligands are cisoid to the
      formamidinate ligand. To illustrate the synthetic scope of the pseudo-Grignard
      reagents, [Yb(Ph2 pz)I(thf)4 ] (Ph2 pz=3,5-diphenylpyrazolate) was oxidised with
      1,2-diiodoethane to afford seven-coordinate monomeric pyrazolato-ytterbium(III)
      iodide [Yb(Ph2 Pz)I2 (thf)3 ] (8) in high yield, whilst metathesis between
      [Yb(Ph2 pz)I(thf)4 ] and NaCp (Cp=C5 H5 ) gave [Yb(C5 H5 )(Ph2 pz)(thf)]n (9), a
      nine-coordinate eta5 :eta5 -Cp-bridged coordination polymer. Reaction of the
      pseudo-Grignard reagent MeYbI with KN(SiMe3 )2 gave [K(dme)4 ][Yb{N(SiMe3 )2 }3 ]
      (10) with a charge-separated three-coordinate homoleptic [Yb{N(SiMe3 )2 }3 ]-
      anion, a complex that could be obtained in high yield by deliberate synthesis
      from YbI2 and KN(SiMe3 )2 in DME.

PMID- 29057572
TI  - Simultaneous analysis by Quadrupole-Orbitrap mass spectrometry and UHPLC-MS/MS
      for the determination of sedative-hypnotics and sleep inducers in adulterated
      products.
AB  - Adulterated products are continuously detected in society and cause problems. In
      this study, we developed and validated a method for determining synthetic
      sedative-hypnotics and sleep inducers, including barbital, benzodiazepam,
      zolpidem, and first-generation antihistamines, in adulterated products using
      Quadrupole-Orbitrap mass spectrometry and ultrahigh performance liquid
      chromatography with tandem mass spectrometry. In Quadrupole-Orbitrap mass
      spectrometry analysis, target compounds were confirmed using a combination of
      retention time, mass tolerance, mass accuracy, and fragment ions. For
      quantification, several validation parameters were employed using ultrahigh
      performance liquid chromatography with tandem mass spectrometry. The limit of
      detection and limit of quantitation was 0.05-53 and 0.17-177 ng/mL, respectively.
      The correlation coefficient for linearity was more than 0.995. The intra- and
      interassay accuracies were 86-110 and 84-111%, respectively. Their precision
      values were evaluated as within 4.0 (intraday) and 10.7% (interday). Mean
      recoveries of target compounds in adulterated products ranged from 85 to 116%.
      The relative standard deviation of stability was less than 10.7% at 4 degrees C
      for 48 h. The 144 adulterated products obtained over 3 years (2014-2016) from
      online and in-person vendors were tested using established methods. After rapidly
      screening with Quadrupole-Orbitrap mass spectrometry, the detected samples were
      quantified using ultrahigh performance liquid chromatography with tandem mass
      spectrometry. Two of them were adulterated with phenobarbital.

PMID- 29057574
TI  - Electric-Field-Controlled Phase Transformation in WO3 Thin Films through Hydrogen
      Evolution.
AB  - Field-effect transistors with ionic-liquid gating (ILG) have been widely employed
      and have led to numerous intriguing phenomena in the last decade, due to the
      associated excellent carrier-density tunability. However, the role of the
      electrochemical effect during ILG has become a heavily debated topic recently.
      Herein, using ILG, a field-induced insulator-to-metal transition is achieved in
      WO3 thin films with the emergence of structural transformations of the whole
      films. The subsequent secondary-ion mass spectrometry study provides solid
      evidence that electrochemically driven hydrogen evolution dominates the
      discovered electrical and structural transformation through surface absorption
      and bulk intercalation.

PMID- 29057573
TI  - Practical guidance for using multiple data sources in systematic reviews and meta
      analyses (with examples from the MUDS study).
AB  - Data for individual trials included in systematic reviews may be available in
      multiple sources. For example, a single trial might be reported in 2 journal
      articles and 3 conference abstracts. Because of differences across sources,
      source selection can influence the results of systematic reviews. We used our
      experience in the Multiple Data Sources in Systematic Reviews (MUDS) study, and
      evidence from previous studies, to develop practical guidance for using multiple
      data sources in systematic reviews. We recommend the following: (1) Specify which
      sources you will use. Before beginning a systematic review, consider which
      sources are likely to contain the most useful data. Try to identify all relevant
      reports and to extract information from the most reliable sources. (2) Link
      individual trials with multiple sources. Write to authors to determine which
      sources are likely related to the same trials. Use a modified Preferred Reporting
      Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart to document
      both the selection of trials and the selection of sources. (3) Follow a
      prespecified protocol for extracting trial characteristics from multiple sources.
      Identify differences among sources, and contact study authors to resolve
      differences if possible. (4) Prespecify outcomes and results to examine in the
      review and meta-analysis. In your protocol, describe how you will handle multiple
      outcomes within each domain of interest. Look for outcomes using all eligible
      sources. (5) Identify which data sources were included in the review. Consider
      whether the results might have been influenced by data sources used. (6) To
      reduce bias, and to reduce research waste, share the data used in your review.

PMID- 29057576
TI  - System-specific activity in response to Delta9 -tetrahydrocannabinol: a
      functional magnetic resonance imaging study in awake male rats.
AB  - The aim of this study was to assess the effects of two doses of Delta9 
      tetrahydrocannabinol (THC, cannabis' main psychoactive agent) and vehicle on
      blood-oxygen-level dependent (BOLD) activity in drug-naive, awake rats, in an
      effort to obtain a THC-specific map of activation in clinically-relevant regions
      and systems. Intraperitoneal injections of low dose of THC resulted in increased
      positive and negative BOLD signals compared to vehicle and high dose in areas
      rich in cannabinoid receptor 1, as well as throughout the pain and hippocampal
      neural systems. These results offer unique maps of activity, or 'fingerprints',
      associated with systemic THC administration, allowing for further comparisons
      with either additional doses or compounds, or between THC administration
      modalities (i.e. systemic vs. ingested vs. inhaled), which ultimately adds to the
      translatability assessment of THC-induced BOLD between animal and human studies.

PMID- 29057578
TI  - Label-free imaging of redox status and collagen deposition showing metabolic
      differences in the heart.
AB  - The heart has high metabolic demand to maintain function. The primary source of
      energy supply to support correct contractile muscle function differs between a
      fetus and an adult. In fetal life, ATP is primarily generated by glycolysis and
      lactate oxidation, whereas following birth, there is a shift towards a reliance
      on mitochondrial metabolism and fatty acid oxidation. This change in metabolic
      status is an adaptation to different fuel availability, oxygenation and growth
      patterns. In this study, we have employed 2-photon excitation fluorescence
      microscopy to define the relationship between two critical metabolic cofactors
      nicotinamide adenine dinucleotide(P)H and flavin adenine dinucleotide,
      effectively utilizing a redox ratio to differentiate between the metabolic status
      in fetal (proliferative) and adult (quiescent/hypertrophic) hearts. Two-photon
      imaging was also used to visually confirm the known increase in collagen
      deposition in the adult heart. The changes observed were consistent with a
      hypertrophic growth profile and greater availability of fatty acids in the adult
      heart, compared to the proliferative fetal heart. Two-photon excitation
      fluorescence microscopy is therefore a convenient imaging technology that enables
      the monitoring of striated muscle architecture and the metabolic status of heart
      tissue. This imaging technology can potentially be employed to visualize cardiac
      and other muscle pathologies.

PMID- 29057579
TI  - Orbitofrontal gray matter deficits as marker of Internet gaming disorder:
      converging evidence from a cross-sectional and prospective longitudinal design.
AB  - Internet gaming disorder represents a growing health issue. Core symptoms include
      unsuccessful attempts to control the addictive patterns of behavior and continued
      use despite negative consequences indicating a loss of regulatory control.
      Previous studies revealed brain structural deficits in prefrontal regions
      subserving regulatory control in individuals with excessive Internet use.
      However, because of the cross-sectional nature of these studies, it remains
      unknown whether the observed brain structural deficits preceded the onset of
      excessive Internet use. Against this background, the present study combined a
      cross-sectional and longitudinal design to determine the consequences of
      excessive online video gaming. Forty-one subjects with a history of excessive
      Internet gaming and 78 gaming-naive subjects were enrolled in the present study.
      To determine effects of Internet gaming on brain structure, gaming-naive subjects
      were randomly assigned to 6 weeks of daily Internet gaming (training group) or a
      non-gaming condition (training control group). At study inclusion, excessive
      Internet gamers demonstrated lower right orbitofrontal gray matter volume
      compared with Internet gaming-naive subjects. Within the Internet gamers, a lower
      gray matter volume in this region was associated with higher online video gaming
      addiction severity. Longitudinal analysis revealed initial evidence that left
      orbitofrontal gray matter volume decreased during the training period in the
      training group as well as in the group of excessive gamers. Together, the present
      findings suggest an important role of the orbitofrontal cortex in the development
      of Internet addiction with a direct association between excessive engagement in
      online gaming and structural deficits in this brain region.

PMID- 29057581
TI  - Genome-wide association studies of bipolar disorder: A systematic review of
      recent findings and their clinical implications.
AB  - Recent advances in molecular genetics have enabled assessments of the
      associations among genetic variants (e.g., single-nucleotide polymorphisms) and
      susceptibility for complex diseases, including psychiatric disorders.
      Specifically, genome-wide association studies (GWAS), meta-analyses of the GWAS
      summary statistics, and mega-analyses (which use raw data, not summary
      statistics) of GWAS have provided revolutionary results and have identified
      numerous susceptibility genes or single-nucleotide polymorphisms. By using
      several tens of thousands of subjects, >40 genes have been identified as being
      associated with susceptibility for bipolar disorder so far. The purpose of this
      systematic review was to summarize the recent findings of bipolar disorder GWAS
      and discuss their clinical implications.

PMID- 29057582
TI  - An exploratory pilot study with copeptin as a biomarker for individualizing
      treatment for nocturnal polyuria.
AB  - OBJECTIVE: The aim of the present study was to investigate the use of random
      copeptin concentrations as possible biomarkers for the differential diagnosis of
      nocturnal polyuria (NP). METHODS: In all, 111 patients with and without nocturia
      were enrolled in the study. Patients with a neurogenic bladder and/or those who
      had undergone bladder or urethral surgery were excluded from the study. All
      patients completed a 72-hour frequency-volume chart and a renal function profile.
      A random blood sample was obtained during the day for measurement of plasma
      copeptin concentrations, osmolality, and serum sodium and creatinine
      concentrations. The effect of the use of different definitions for NP was
      evaluated. RESULTS: The median age of the study participants was 61 years, and
      48% were female. Copeptin was significantly correlated with urinary and plasma
      osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively;
      P < .001 for all). Study participants were divided into 3 groups: controls (n =
      51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin
      concentrations were significantly lower in subjects with global polyuria than in
      those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P =
      .008 and .005). There was no significant difference in random daytime copeptin
      concentrations between the NP and control groups (P = .972). The results differed
      when other definitions for NP were used (e.g. NPi33 or NUP10). CONCLUSIONS: We
      could not confirm our hypothesis that patients with NP have lower copeptin
      concentrations, although random blood sampling is not ideal. Further research is
      required to determine the use of copeptin in NP, perhaps in the identification of
      the desmopressin response.

PMID- 29057583
TI  - A medical device containing purified bovine colostrum (Monurelle Biogel) in the
      treatment of vulvovaginal atrophy in postmenopausal women: Retrospective analysis
      of urinary symptoms, sexual function, and quality of life.
AB  - OBJECTIVE: This study assessed the effectiveness and safety of a medical device
      containing purified bovine colostrum (Monurelle Biogel; Zambon, Bresso, Italy) in
      improving vulvovaginal atrophy (VVA), sexual function, urinary symptoms, and
      quality of life (QoL) in postmenopausal women. METHODS: In all, 172
      postmenopausal women with VVA were included in the study. All women were treated
      with vaginal Monurelle Biogel daily for 12 weeks. Patients underwent clinical
      examinations, completed a 3-day voiding diary, and had VVA graded using the
      Vaginal Health Index (VHI) at baseline and 12 weeks. Patients also completed the
      Female Sexual Function Index (FSFI), overactive bladder questionnaire (OAB-Q),
      and the Urogenital Distress Inventory (UDI-6), among others. RESULTS: After 12
      weeks, there were significant increases in mean (+/- SD) VHI (12.53 +/- 3.67 vs.
      19.31 +/- 3.49; P < .0001), the number of patients engaging in regular sexual
      activity 102 (59.3%) vs. 144 (83.7%), and in the total FSFI score (21.64 +/- 2.99
      vs. 28.16 +/- 1.93; P < .0001) compared with baseline. In addition, there were
      significant reductions in the mean number of 24-hour voids (9.57 +/- 2.12 vs.
      7.13 +/- 1.22; P < .0001), urgent micturition episodes per 24 hours (1.75 +/-
      0.76 vs. 1.14 +/- 0.87; P = .001), nocturia episodes (1.58 +/- 0.85 vs. 0.97 +/-
      1.18; P = .0002), and urinary incontinence episodes per 24 hours (0.74 +/- 0.59
      vs. 0.28 +/- 0.52; P = .003). Finally, after 12 weeks treatment, there were
      significant differences in UDI-6 (7.85 +/- 0.81 vs. 5.56 +/- 1.40), OAB-Q symptom
      (53.60 +/- 12.57 vs. 22.08 +/- 9.63), and OAB-Q health-related QoL (21.75 +/-
      8.51 vs. 69.34 +/- 14.59) scores compared with baseline (P < .0001 for all). The
      Patient Impression of Global Improvement scale revealed global improvement in 143
      women (83.14%). CONCLUSIONS: Monurelle Biogel is an effective treatment for VVA
      in postmenopausal women, improving sexual life, urinary symptoms, and QoL.

PMID- 29057584
TI  - Sixty years ago: The birth of The Journal of Medical Imaging and Radiation
      Oncology.

PMID- 29057586
TI  - Mercury levels in hair samples of dentists: A comparative study in Sri Lanka.
AB  - AIM: Elemental mercury is widely used in dentistry as dental amalgam. Hair
      samples constitute preferred biomarkers to determine the index of mercury
      exposure. In the absence of any published studies, the aim of the present study
      was to ascertain the level of mercury in a selected sample of dentists and
      controls in Sri Lanka. METHODS: Hair samples (.7 g) from dentists working in and
      around the Colombo district in Sri Lanka (n = 50) and controls (n = 50) were
      digested with sulfuric acid-potassium permanganate solution, and reduced to
      metallic mercury with stannous chloride. Digested samples were analyzed for
      mercury using an atomic absorption spectrophotometer. RESULTS: The average
      mercury contents of the test and control samples (n = 50 each) were 5.36 +/- 2.64
      ppb and 3.1 +/- 1.99 ppb, respectively. Based on the estimated ratio of mercury
      in hair to blood in humans as 250:1, the average content of mercury in the blood
      of the two groups could be .02 ppb and .01 ppb, respectively. The number of years
      in dentistry and number of amalgam restorations performed within 1 week were not
      correlated with the hair concentration of mercury. CONCLUSIONS: As the values of
      both groups were well below 10 ng/mL (10 ppb), within the concentrations
      considered as normal, mercury use was not considered an occupational hazard for
      dentists.

PMID- 29057585
TI  - Response of marine bacteria to oil contamination and to high pressure and low
      temperature deep sea conditions.
AB  - The effect of pressure and temperature on microbial communities of marine
      environments contaminated with petroleum hydrocarbons is understudied. This study
      aims to reveal the responses of marine bacterial communities to low temperature,
      high pressure, and contamination with petroleum hydrocarbons using seawater
      samples collected near an offshore Brazilian platform. Microcosms containing only
      seawater and those containing seawater contaminated with 1% crude oil were
      subjected to three different treatments of temperature and pressure as follows:
      (1) 22 degrees C/0.1 MPa; (2) 4 degrees C/0.1 MPa; and (3) 4 degrees C/22 MPa.
      The effect of depressurization followed by repressurization on bacterial
      communities was also evaluated (4 degrees C/22 MPaD). The structure and
      composition of the bacterial communities in the different microcosms were
      analyzed by PCR-DGGE and DNA sequencing, respectively. Contamination with oil
      influenced the structure of the bacterial communities in microcosms incubated
      either at 4 degrees C or 22 degrees C and at low pressure. Incubation at low
      temperature and high pressure greatly influenced the structure of bacterial
      communities even in the absence of oil contamination. The 4 degrees C/22 MPa and
      4 degrees C/22 MPaD treatments resulted in similar DGGE profiles. DNA sequencing
      (after 40 days of incubation) revealed that the diversity and relative abundance
      of bacterial genera were related to the presence or absence of oil contamination
      in the nonpressurized treatments. In contrast, the variation in the relative
      abundances of bacterial genera in the 4 degrees C/22 MPa-microcosms either
      contaminated or not with crude oil was less evident. The highest relative
      abundance of the phylum Bacteroidetes was observed in the 4 degrees C/22 MPa
      treatment.

PMID- 29057587
TI  - In Silico Prediction of Compounds Binding to Human Plasma Proteins by QSAR
      Models.
AB  - Plasma protein binding (PPB) is a significant pharmacokinetic property of
      compounds in drug discovery and design. Due to the high cost and time-consuming
      nature of experimental assays, in silico approaches have been developed to assess
      the binding profiles of chemicals. However, because of unambiguity and the lack
      of uniform experimental data, most available predictive models are far from
      satisfactory. In this study, an elaborately curated training set containing 967
      diverse pharmaceuticals with plasma-protein-bound fractions (fb ) was used to
      construct quantitative structure-activity relationship (QSAR) models by six
      machine learning algorithms with 26 molecular descriptors. Furthermore, we
      combined all of the individual learners to yield consensus prediction, marginally
      improving the accuracy of the consensus model. The model performance was
      estimated by tenfold cross validation and three external validation sets
      comprising 242 pharmaceutical, 397 industrial, and 231 newly designed chemicals,
      respectively. The models showed excellent performance for the entire test set,
      with mean absolute error (MAE) ranging from 0.126 to 0.178, demonstrating that
      our models could be used by a chemist when drawing a molecular structure from
      scratch. Meanwhile, structural descriptors contributing significantly to the
      predictive power of the models were related to the binding mechanisms, and the
      trend in terms of their effects on PPB can serve as guidance for the structural
      modification of chemicals. The applicability domain was also defined to
      distinguish favorable predictions from unfavorable predictions.

PMID- 29057588
TI  - GUB06-046, a novel secretin/glucagon-like peptide 1 co-agonist, decreases food
      intake, improves glycemic control, and preserves beta cell mass in diabetic mice.
AB  - Bariatric surgery is currently the most effective treatment of obesity, which has
      spurred an interest in developing pharmaceutical mimetics. It is thought that the
      marked body weight-lowering effects of bariatric surgery involve stimulated
      secretion of appetite-regulating gut hormones, including glucagon-like peptide 1.
      We here report that intestinal expression of secretin is markedly upregulated in
      a rat model of Roux-en-Y gastric bypass, suggesting an additional role of
      secretin in the beneficial metabolic effects of Roux-en-Y gastric bypass. We
      therefore developed novel secretin-based peptide co-agonists and identified a
      lead compound, GUB06-046, that exhibited potent agonism of both the secretin
      receptor and glucagon-like peptide 1 receptor. Semi-acute administration of GUB06
      046 to lean mice significantly decreased cumulative food intake and improved
      glucose tolerance. Chronic administration of GUB06-046 to diabetic db/db mice for
      8 weeks improved glycemic control, as indicated by a 39% decrease in fasting
      blood glucose and 1.6% reduction of plasma HbA1c levels. Stereological analysis
      of db/db mice pancreata revealed a 78% increase in beta-cell mass after GUB06-046
      treatment, with no impact on exocrine pancreas mass or pancreatic duct epithelial
      mass. The data demonstrate beneficial effects of GUB06-046 on appetite
      regulation, glucose homeostasis, and beta-cell mass in db/db mice, without
      proliferative effects on the exocrine pancreas and the pancreatic duct
      epithelium. Copyright (c) 2017 European Peptide Society and John Wiley & Sons,
      Ltd.

PMID- 29057590
TI  - Excision of conjunctival melanosis and conjunctival autografting by femtosecond
      laser.

PMID- 29057589
TI  - Maternal Affective Expression and Adolescents' Subjective Experience of Positive
      Affect in Natural Settings.
AB  - This study investigated the association between maternal affective expression
      during laboratory-based interaction tasks and adolescents' experience of positive
      affect (PA) in natural settings. Participants were 80 healthy adolescents and
      their mothers. Durations of maternal positive (PA) and negative affective (NA)
      expressions were observed during a conflict resolution task and a positive event
      planning interaction task. Ecological momentary assessment (EMA) procedures were
      employed to assess adolescents' momentary and peak experience of PA in daily
      life. Results indicated that maternal NA, but not maternal PA, was related to
      adolescents' EMA-reported PA. Adolescents whose mothers expressed more NA
      experienced less PA in daily environments. Results suggest that adolescents'
      exposure to maternal negative affective behavior is associated with adolescents'
      subjective daily well-being.

PMID- 29057591
TI  - Self-Assembly of Chiral Gold Clusters into Crystalline Nanocubes of Exceptional
      Optical Activity.
AB  - Self-assembly of inorganic nanoparticles into ordered structures is of interest
      in both science and technology because it is expected to generate new properties
      through collective behavior; however, such nanoparticle assemblies with
      characteristics distinct from those of individual building blocks are rare.
      Herein we use atomically precise Au clusters to make ordered assemblies with
      emerging optical activity. Chiral Au clusters with strong circular dichroism (CD)
      but free of circularly polarized luminescence (CPL) are synthesized and organized
      into uniform body-centered cubic (BCC) packing nanocubes. Once the ordered
      structure is formed, the CD intensity is significantly enhanced and a remarkable
      CPL response appears. Both experiment and theory calculation disclose that the
      CPL originates from restricted intramolecular rotation and the ordered stacking
      of the chiral stabilizers, which are fastened in the crystalline lattices.

PMID- 29057592
TI  - The role of sialic acids in the immune recognition of xenografts.
AB  - Presentation of sialic acid (Sia) varies among different tissues and organs
      within each species, and between species. This diversity has biologically
      important consequences regarding the recognition of cells by "xeno" antibodies
      (Neu5Gc vs Neu5Ac). Sia also plays a central role in inflammation by influencing
      binding of the asialoglycoprotein receptor 1 (ASGR-1), Siglec-1 (Sialoadhesin),
      and cellular interactions mediated by the selectin, integrin, and galectin
      receptor families. This review will focus on what is known about basic Sia
      structure and function in association with xenotransplantation, how changes in
      sialylation may occur in this context (through desialylation or changes in
      sialyltransferases), and how this fundamental pathway modulates adhesive and cell
      activation pathways that appear to be particularly crucial to homeostasis and
      inflammation for xenografts.

PMID- 29057593
TI  - Optimized Synthesis of ZSM-11 Catalysts using 1,8-Diaminooctane as a Structure
      Directing Agent.
AB  - Developing new zeolite catalysts for (petro)chemical applications is nontrivial
      owing to challenges that include the identification of commercially-viable
      syntheses. The vast majority of syntheses require the use of an organic structure
      directing agent (OSDA), which has economic and environmental shortcomings. In the
      search for alternative zeolites to common industrial catalysts, such as ZSM-5
      (MFI), a promising candidate is ZSM-11 (MEL), a close structural analogue of MFI.
      ZSM-11 is comprised of 3-dimensional straight channels that have less diffusion
      limitations than MFI. Side-by-side comparisons of ZSM-11 and ZSM-5 catalysts
      reveal the former exhibits significantly longer time-on-stream lifetime in many
      reactions; however, there are several difficulties associated with the
      preparation of ZSM-11, which include the ability to identify inexpensive OSDAs
      that produce small crystals in high yield. Here, we examine ZSM-11 synthesis
      using 1,8-diaminooctane (DAO), which produces ZSM-11 crystals with sizes of ca.
      300 nm. We demonstrate that the use of MEL seeds allows for an order of magnitude
      reduction in the quantity of DAO without sacrificing crystal purity or yield (>80
      %). Catalytic tests using methanol to hydrocarbons as a representative reaction
      show that H-ZSM-11 lifetime and selectivity are similar for samples prepared with
      and without seeds. Collectively our findings highlight an efficient method to
      produce ZSM-11 as a potential alternative to ZSM-5 for catalytic applications.

PMID- 29057594
TI  - Phase Equilibrium of TiO2 Nanocrystals in Flame-Assisted Chemical Vapor
      Deposition.
AB  - Nano-scale titanium oxide (TiO2 ) is a material useful for a wide range of
      applications. In a previous study, we showed that TiO2 nanoparticles of both
      rutile and anatase crystal phases could be synthesized over the size range of 5
      to 20 nm in flame-assisted chemical vapor deposition. Rutile was unexpectedly
      dominant in oxygen-lean synthesis conditions, whereas anatase is the preferred
      phase in oxygen-rich gases. The observation is in contrast to the 14 nm rutile
      anatase crossover size derived from the existing crystal-phase equilibrium model.
      In the present work, we made additional measurements over a wider range of
      synthesis conditions; the results confirm the earlier observations. We propose an
      improved model for the surface energy that considers the role of oxygen
      desorption at high temperatures. The model successfully explains the observations
      made in the current and previous work. The current results provide a useful path
      to designing flame-assisted chemical vapor deposition of TiO2 nanocrystals with
      controllable crystal phases.

PMID- 29057595
TI  - Aseptic surgical preparation for upper eyelid blepharoplasty via full-face
      octenidine antiseptic without antibiotic medication shows effective prophylaxis
      against post-surgical wound infection.
AB  - Blepharoplasty is the third most common plastic surgical procedure in the USA.
      Due to the emergence of multiresistant bacteria, optimising the antiseptic
      procedure is crucial. Choice of antiseptics plays an important role as they may
      cause skin irritation and colouring of disinfected areas. In this study, the use
      of the aqueous antiseptic octenisept(r) (octenidine) was evaluated in the outcome
      of blepharoplasties: incidence of wound dehiscence; haematoma; and infection in
      correlation with gender, medication, smoking habits and time of year. This
      retrospective surveillance study included 352 patients (median age 58.3 years).
      Skin disinfection was performed thrice prior to blepharoplasty. Sutures were
      removed on day 6. None of the patients suffered from wound infection. The total
      rate of wound dehiscence was 6.3%, with a higher ratio among male patients.
      Smokers and patients on anticoagulant medication showed a significantly higher
      incidence of wound dehiscence. Throughout the year, rates of wound dehiscence
      were highest in summer. Aseptic surgical preparation for blepharoplasty via full
      face scrub with octenisept(r) without oral antibiotic prophylaxis is well
      tolerated, with no report of wound infection, which may improve antibiotic
      stewardship as well as patient comfort. Elective upper eyelid blepharoplasty may
      ideally be performed in winter.

PMID- 29057596
TI  - The Anaclitic-Introjective Depression Assessment: Development and preliminary
      validity of an observer-rated measure.
AB  - BACKGROUND: The two-configurations model developed by Blatt and colleagues offers
      a comprehensive conceptual and empirical framework for understanding depression.
      This model suggests that depressed patients struggle, at different developmental
      levels, with issues related to dependency (anaclitic issues) or self-definition
      (introjective issues), or a combination of both. AIMS: This paper reports three
      studies on the development and preliminary validation of the Anaclitic
      Introjective Depression Assessment, an observer-rated assessment tool of
      impairments in relatedness and self-definition in clinical depression based on
      the item pool of the Shedler-Westen Assessment Procedure. METHOD: Study 1
      describes the development of the measure using expert consensus rating and Q
      methodology. Studies 2 and 3 report the assessment of its psychometric
      properties, preliminary reliability, and validity in a sample of 128 patients
      diagnosed with treatment-resistant depression. RESULTS: Four naturally occurring
      clusters of depressed patients were identified using Q-factor analysis, which,
      overall, showed meaningful and theoretically expected relationships with
      anaclitic/introjective prototypes as formulated by experts, as well as with
      clinical, social, occupational, global, and relational functioning. CONCLUSION:
      Taken together, findings reported in this paper provide preliminary evidence for
      the reliability and validity of the Anaclitic-Introjective Depression Assessment,
      an observer-rated measure that allows the detection of important nuanced
      differentiations between and within anaclitic and introjective depression.

PMID- 29057597
TI  - Atypical Hemolytic Uremic Syndrome in Low Resource Settings: Which Options Do We
      Have?

PMID- 29057598
TI  - Separation of structurally related primary aliphatic amines using hydrophilic
      interaction chromatography with fluorescence detection after postcolumn
      derivatization with o-phthaldialdehyde/mercaptoethanol.
AB  - The retention behavior of primary aliphatic amines (homologous series of
      aliphatic alkyl amines and cycloalkyl amines) and positional isomers of
      alkylamines in the hydrophilic interaction chromatography mode was studied. The
      study was carried out on a TSKgel Amide-80 column followed by postcolumn
      derivatization with fluorescence detection to describe the retention mechanism of
      tested compounds. The effect of chromatographic conditions including column
      temperature, acetonitrile content in the mobile phase, mobile phase pH (ranging
      from 3.5 to 6.8), and salt concentration in the mobile phase was investigated.
      The final mobile phase consisted of acetonitrile and solution of 20 mM potassium
      formate pH 3.5 in ratio 80:20 v/v. The analyses were carried out at mobile phase
      flow rate of 1.0 mL/min and the column temperature of 20 degrees C. The developed
      method was fully validated in terms of linearity, sensitivity (limit of detection
      and limit of quantification), accuracy, and precision according to International
      Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human
      Use guidelines. The proposed new methods were proved to be highly sensitive,
      simple, and rapid, and were successfully applied to the determinations of
      isopropylamine, cyclohexylamine, and cyclopropylamine in relevant active
      pharmaceutical ingredients.

PMID- 29057599
TI  - Erratum.

PMID- 29057601
TI  - Investigating Body Image Disturbance in Anorexia Nervosa Using Novel Biometric
      Figure Rating Scales: A Pilot Study.
AB  - This study uses novel biometric figure rating scales (FRS) spanning body mass
      index (BMI) 13.8 to 32.2 kg/m2 and BMI 18 to 42 kg/m2 . The aims of the study
      were (i) to compare FRS body weight dissatisfaction and perceptual distortion of
      women with anorexia nervosa (AN) to a community sample; (ii) how FRS parameters
      are associated with questionnaire body dissatisfaction, eating disorder symptoms
      and appearance comparison habits; and (iii) whether the weight spectrum of the
      FRS matters. Women with AN (n = 24) and a community sample of women (n = 104)
      selected their current and ideal body on the FRS and completed additional
      questionnaires. Women with AN accurately picked the body that aligned best with
      their actual weight in both FRS. Controls underestimated their BMI in the FRS 14
      32 and were accurate in the FRS 18-42. In both FRS, women with AN desired a body
      close to their actual BMI and controls desired a thinner body. Our observations
      suggest that body image disturbance in AN is unlikely to be characterized by a
      visual perceptual disturbance, but rather by an idealization of underweight in
      conjunction with high body dissatisfaction. The weight spectrum of FRS can
      influence the accuracy of BMI estimation. Copyright (c) 2017 John Wiley & Sons,
      Ltd and Eating Disorders Association.

PMID- 29057600
TI  - Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism and Eating Disorders:
      Data From a New Biobank and Meta-Analysis of Previously Published Studies.
AB  - OBJECTIVES: We investigated whether catechol-O-methyltransferase (COMT) Val158Met
      polymorphism is associated with eating disorders (EDs). METHODS: We conducted a
      systematic literature search of studies published until 15 January 2017 and added
      data from the Italian 'Biobanca Veneta per i Disturbi Alimentari' biobank,
      performing a meta-analysis comparing COMT Val158Met genotype and allele
      frequencies in EDs and anorexia nervosa (AN) or bulimia nervosa (BN) patients
      versus controls. RESULTS: Ten studies plus Biobanca Veneta per i Disturbi
      Alimentari (ED: n = 920, controls: n = 261 controls) with 3541 ED patients (AN =
      2388; BN = 233) and 3684 controls were included. There were no significant group
      differences in COMT Val158Met alleles and genotype frequencies between patients
      and controls, for all EDs pooled together [range of odds ratios (ORs): 0.96-1.04,
      p-values: 0.46-0.97, I2  = 0%] and when analysing separately patients with AN
      (ORs: 0.94-1.04, p-values: 0.31-0.61, I2  = 0%) or BN (ORs: 0.80-1.09, p-values:
      0.28-0.64, I2  = 0-44%). CONCLUSIONS: Meta-analysing data results from 11 studies
      and 7225 subjects show that COMT Val158Met polymorphism is not associated with
      EDs. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 29057602
TI  - Detecting Eating Psychopathology in Female Athletes by Asking About Exercise: Use
      of the Compulsive Exercise Test.
AB  - The present study assessed the suitability of the Compulsive Exercise Test
      (athlete version; CET-A) for identifying female athletes with clinically
      significant features related to or comparable with eating psychopathology. Three
      hundred and sixty-one female athletes (including 12 with a clinically diagnosed
      eating disorder) completed the Eating Disorders Examination Questionnaire and the
      CET-A. Receiver operating curve analysis was employed to identify a cut-off value
      on the CET-A, which could indicate clinically significant features related to or
      comparable with eating psychopathology among female athletes. The analysis
      demonstrated that a CET-A score of 10 successfully discriminated female athletes
      with a current eating disorder. The results suggest that the CET-A may be a
      suitable tool for detecting eating psychopathology in female athletes. Additional
      longitudinal research is needed to evaluate the predictive value of the CET-A.
      Copyright (c) 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 29057603
TI  - Delay Discounting of Reward and Impulsivity in Eating Disorders: From Anorexia
      Nervosa to Binge Eating Disorder.
AB  - Evidence points to eating disorder patients displaying altered rates of delay
      discounting (one's degree of preference for immediate rewards over larger delayed
      rewards). Anorexia nervosa (AN) patients are believed to have an increased
      capacity to delay reward, which reflects their ability to override the drive to
      eat. Contrarily, binge eating disorder (BED) patients are associated with a
      reduced predisposition to delay gratification. Here, we investigated monetary
      delay discounting and impulsivity in 80 adult women with EDs (56 AN and 24 BED),
      diagnosed according to Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition criteria, and 80 healthy controls. AN-restrictive (AN-R) subtype
      patients showed less steep discounting rates than BED and AN-bingeing/purging
      subtype patients. Compared with healthy controls and AN-R patients, BED and AN
      bingeing/purging patients presented higher delay discounting and positive and
      negative urgency levels. Our findings suggest that restriction in AN-R patients
      is associated with disproportionate self-control, whereas bingeing behaviours
      could be more driven by emotional states and impulsivity traits. Copyright (c)
      2017 John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 29057605
TI  - Putative Risk Factors for Non-Suicidal Self-Injury in Eating Disorders.
AB  - Evidence suggests a common association between eating disorders (EDs) and non
      suicidal self-injury (NSSI). The present study aimed to investigate the potential
      risk factors for NSSI among ED patients. We assessed 245 ED patients with the
      Oxford Risk Factor Interview for ED. The results showed that 33% of ED patients
      reported NSSI in their lifetime. NSSI appeared to occur more frequently among
      binge eating/purging type ED patients than among patients with other ED and to be
      related to a more severe eating pathology. A younger age at the onset of eating
      problems, more negative self-evaluation, suicide attempts, substance abuse,
      parents' low weight, family tension at mealtime, parental alcohol problems,
      childhood abuse, peer aggression, and negative antecedent life events were more
      common among patients with co-occurring EDs and NSSI than among patients without
      NSSI. The results may inform the risk assessment and treatment of NSSI in EDs in
      the early detection period. Copyright (c) 2017 John Wiley & Sons, Ltd and Eating
      Disorders Association.

PMID- 29057604
TI  - Perfectionism Group Treatment for Eating Disorders in an Inpatient, Partial
      Hospitalization, and Outpatient Setting.
AB  - Perfectionism is elevated in individuals with eating disorders and is posited to
      be a risk factor, maintaining factor, and treatment barrier. However, there has
      been little literature testing the feasibility and effectiveness of perfectionism
      interventions in individuals specifically with eating disorders in an open group
      format. In the current study, we tested the feasibility of (a) a short cognitive
      behavioural therapy for perfectionism intervention delivered in an inpatient,
      partial hospitalization, and outpatient for eating disorders setting (combined N
      = 28; inpatient n = 15; partial hospital n = 9; outpatient n = 4), as well as (b)
      a training for disseminating the treatment in these settings (N = 9). Overall, we
      found that it was feasible to implement a perfectionism group in each treatment
      setting, with both an open and closed group format. This research adds additional
      support for the implementation of perfectionism group treatment for eating
      disorders and provides information on the feasibility of implementing such
      interventions across multiple settings. Copyright (c) 2017 John Wiley & Sons, Ltd
      and Eating Disorders Association.

PMID- 29057606
TI  - Ultrathin Layered SnSe Nanoplates for Low Voltage, High-Rate, and Long-Life
      Alkali-Ion Batteries.
AB  - 2D electrode materials with layered structures have shown huge potential in the
      fields of lithium- and sodium-ion batteries. However, their poor conductivity
      limits the rate performance and cycle stability of batteries. Herein a new
      colloid chemistry strategy is reported for making 2D ultrathin layered SnSe
      nanoplates (SnSe NPs) for achieving more efficient alkali-ion batteries. Due to
      the effect of weak Van der Waals forces, each semiconductive SnSe nanoplate
      stacks on top of each other, which can facilitate the ion transfer and
      accommodate volume expansion during the charge and discharge process. This unique
      structure as well as the narrow-bandgap semiconductor property of SnSe
      simultaneously meets the requirements of achieving fast ionic and electronic
      conductivities for alkali-ion batteries. They exhibit high capacity of 463.6 mAh
      g-1 at 0.05 A g-1 for Na-ion batteries and 787.9 mAh g-1 at 0.2 A g-1 for Li-ion
      batteries over 300 cycles, and also high stability for alkali-ion batteries.

PMID- 29057607
TI  - Detection of monoclonal B cells in general population from two different regions
      of Mexico.
AB  - To estimate the frequency of monoclonal B cells in Mexican general population
      from two different regions of Mexico. Monoclonal B cells were detected by
      rearrangements of the immunoglobulin heavy chains (IGH) in 288 individuals: 188
      from a metropolitan area and 100 from a rural area. After DNA extraction from
      peripheral blood by the CTAB/DTAB method, multiplex PCR was used to amplify the
      IGH rearrangements, followed by capillary electrophoresis. In together, 9.4% of
      the studied individuals showed monoclonal B cells. This prevalence is
      significantly higher to those previously described for other populations, but
      similar to a report in the Spanish population. Among people from the metropolitan
      area, 12.8% exhibited monoclonal B cells in comparison with 3% of people from the
      rural area. All individuals showing monoclonal B cells were elder than 40 years.
      Higher frequency of incomplete monoclonal rearrangements was observed.
      Individuals from urban areas show significantly increased frequencies of
      monoclonal B cells regarding the people from the rural area. It is reasonable to
      believe that the environmental factor could have a greater impact on the
      development of monoclonality than the genetic component.

PMID- 29057608
TI  - Current immunogenetic predisposition to tuberculosis in the Moroccan population.
AB  - Tuberculosis (TB) is a serious infectious disease that kills approximately two
      million people per year, particularly in low- and middle-income countries.
      Numerous genetic epidemiology studies have been conducted of many ethnic groups
      worldwide and have highlighted the critical impact of the genetic environment on
      TB distribution. Many candidate genes associated with resistance or
      susceptibility to TB have been identified. In Morocco, where TB is still a major
      public health problem, various observations of clinical, microbiological and
      incidence distribution are heavily affected by genetic background and external
      environment. Morocco has almost the same clinical profile as do other North
      African countries, mainly the increase in more extrapulmonary than pulmonary
      forms of the diseases, when compared to European, Asian or American populations.
      In addition, a linkage analysis study that examined Moroccan TB patients
      identified a unique chromosome region that had a strong association with the risk
      of contracting TB. Other genes in the Moroccan population that were found to be
      associated seem to be involved predominantly in modulating the innate immunity.
      In this review, we appraise the major candidate genes that have been reported in
      Moroccan immunogenetic studies and discuss their updated role in TB, particularly
      during the first phase of the immune response to Mycobacterium tuberculosis (Mtb)
      infection.

PMID- 29057609
TI  - The efficacy of removable devices to offload and heal neuropathic plantar
      forefoot ulcers in people with diabetes: a single-blinded multicentre randomised
      controlled trial.
AB  - Non-removable offloading is the 'gold standard' treatment for neuropathic
      diabetic plantar forefoot ulcers. However, removable offloading is the common
      'standard of care'. We compared three removable offloading devices for ulcer
      healing efficacy. In this multicentre, randomised controlled trial, 60 persons
      with neuropathic diabetic plantar forefoot ulcers were randomly assigned to wear
      a custom-made knee-high cast [BTCC (bivalved TCC)], custom-made ankle-high cast
      shoe or a prefabricated ankle-high forefoot-offloading shoe (FOS). Primary
      outcome was healing at 12 weeks. Dynamic plantar pressures, daily stride count
      and treatment adherence were assessed on a randomly selected subset (n = 35).
      According to intention-to-treat analysis, 58% of patients healed with BTCC [OR
      0.77 (95% CI 0.41-1.45) versus FOS], 60% with cast shoe [OR 0.81 (95% CI 0.44
      1.49) versus FOS] and 70% with FOS (P = 0.70). Mean +/- SD peak pressure in kPa
      at the ulcer site was 81 +/- 55 for BTCC, 176 +/- 80 for cast shoe and 107 +/- 52
      for FOS (P = 0.005); stride count was 4150 +/- 1626, 3514 +/- 1380 and 4447 +/-
      3190, respectively (P = 0.71); percentage of 2-week intervals that patients wore
      the device <50% of time was 17.3%, 5.2% and 4.9%, respectively. Non-significant
      differences in healing efficacy between the three devices suggest that, when non
      removable offloading is contraindicated or not available, each can be used for
      plantar forefoot ulcer offloading. Efficacy is lower than previously found for
      non-removable offloading maybe because suboptimal adherence and high stride count
      expose the patient to high repetitive stresses. These factors should be carefully
      considered in decision making regarding ulcer treatment.

PMID- 29057611
TI  - Comparison of Maximum Common Subgraph Isomorphism Algorithms for the Alignment of
      2D Chemical Structures.
AB  - The identification of the largest substructure in common when two (or more)
      molecules are overlaid is important for several applications in chemoinformatics,
      and can be implemented using a maximum common subgraph (MCS) algorithm. Many such
      algorithms have been reported, and it is important to know which are likely to be
      the useful in operation. A detailed comparison was hence conducted of the
      efficiency (in terms of CPU time) and the effectiveness (in terms of the size of
      the MCS identified) of eleven MCS algorithms, some of which were exact and some
      of which were approximate in character. The algorithms were used to identify both
      connected and disconnected MCSs on a range of pairs of molecules. The fastest
      exact algorithms for the connected and disconnected problems were found to be the
      fMCS and MaxCliqueSeq algorithms, respectively, while the ChemAxon_MCS algorithm
      was the fastest approximate algorithm for both types of problem.

PMID- 29057610
TI  - Swimming and rafting of E.coli microcolonies at air-liquid interfaces.
AB  - The dynamics of swimming microorganisms is strongly affected by solid-liquid and
      air-liquid interfaces. In this paper, we characterize the motion of both single
      bacteria and microcolonies at an air-liquid interface. Both of them follow
      circular trajectories. Single bacteria preferentially show a counter-clockwise
      motion, in agreement with previous experimental and theoretical findings.
      Instead, no preferential rotation direction is observed for microcolonies
      suggesting that their motion is due to a different physical mechanism. We propose
      a simple mechanical model where the microcolonies move like rafts constrained to
      the air-liquid interface. Finally, we observed that the microcolony growth is due
      to the aggregation of colliding single-swimmers, suggesting that the microcolony
      formation resembles a condensation process where the first nucleus originates by
      the collision between two single-swimmers. Implications of microcolony splitting
      and aggregation on biofilm growth and dispersion at air-liquid interface are
      discussed.

PMID- 29057612
TI  - Rapid response to changing environments during biological invasions: DNA
      methylation perspectives.
AB  - Dissecting complex interactions between species and their environments has long
      been a research hot spot in the fields of ecology and evolutionary biology. The
      well-recognized Darwinian evolution has well-explained long-term adaptation
      scenarios; however, "rapid" processes of biological responses to environmental
      changes remain largely unexplored, particularly molecular mechanisms such as DNA
      methylation that have recently been proposed to play crucial roles in rapid
      environmental adaptation. Invasive species, which have capacities to successfully
      survive rapidly changing environments during biological invasions, provide great
      opportunities to study molecular mechanisms of rapid environmental adaptation.
      Here, we used the methylation-sensitive amplified polymorphism (MSAP) technique
      in an invasive model ascidian, Ciona savignyi, to investigate how species
      interact with rapidly changing environments at the whole-genome level. We
      detected quite rapid DNA methylation response: significant changes of DNA
      methylation frequency and epigenetic differentiation between treatment and
      control groups occurred only after 1 hr of high-temperature exposure or after 3
      hr of low-salinity challenge. In addition, we detected time-dependent
      hemimethylation changes and increased intragroup epigenetic divergence induced by
      environmental stresses. Interestingly, we found evidence of DNA methylation
      resilience, as most stress-induced DNA methylation variation maintained shortly
      (~48 hr) and quickly returned back to the control levels. Our findings clearly
      showed that invasive species could rapidly respond to acute environmental changes
      through DNA methylation modifications, and rapid environmental changes left
      significant epigenetic signatures at the whole-genome level. All these results
      provide fundamental background to deeply investigate the contribution of DNA
      methylation mechanisms to rapid contemporary environmental adaptation.

PMID- 29057614
TI  - Below-ground organic matter accumulation along a boreal forest fertility gradient
      relates to guild interaction within fungal communities.
AB  - Plant-soil interactions link ecosystem fertility and organic matter accumulation
      below ground. Soil microorganisms play a central role as mediators of these
      interactions, but mechanistic understanding is still largely lacking. Correlative
      data from a coniferous forest ecosystem support the hypothesis that interactions
      between fungal guilds play a central role in regulating organic matter
      accumulation in relation to fertility. With increasing ecosystem fertility, the
      proportion of saprotrophic basidiomycetes increased in deeper organic layers, at
      the expense of ectomycorrhizal fungal species. Saprotrophs correlated positively
      with the activity of oxidative enzymes, which in turn favoured organic matter
      turnover and nitrogen recycling to plants. Combined, our findings are consistent
      with a fungus-mediated feedback loop, which results in a negative correlation
      between ecosystem fertility and below-ground carbon storage. These findings call
      for a shift in focus from plant litter traits to fungal traits in explaining
      organic matter dynamics and ecosystem fertility in boreal forests.

PMID- 29057613
TI  - secA, secD, secF, yajC, and yidC contribute to the adhesion regulation of Vibrio
      alginolyticus.
AB  - Vibrio alginolyticus caused great losses to aquaculture. Adhesion is an important
      virulence factor of V. alginolyticus. In this study, the relationship between V.
      alginolyticus adhesion and type II secretion system genes (secA, secD, secF,
      yajC, and yidC) was determined using gene silencing, qRT-PCR and in vitro
      adhesion assay. The results showed that the expression of target genes and the
      bacterial adhesion exhibited significant decreases after transient gene silencing
      and stable gene silencing, which indicated that secA, secD, secF, yajC, and yidC
      played roles in the bacterial adhesion of V. alginolyticus. The expression of
      secA, secD, secF, yajC, and yidC were significantly influenced by temperature,
      salinity, pH and starvation. The results indicated that the expression of secA,
      secD, secF, yajC, and yidC were sensitive to different environmental factors,
      whereas environmental factors can affect V. alginolyticus adhesion via the
      expression of secA, secD, secF, yajC, and yidC.

PMID- 29057615
TI  - Systematic review of the psychometric properties of disease-specific, quality-of
      life questionnaires for patients with hepatobiliary or pancreatic cancers.
AB  - AIM: To systematically review the quality of the psychometric properties of
      disease-specific quality-of-life questionnaires for patients with hepatobiliary
      or pancreatic cancers in order to help researchers and clinicians to select the
      most appropriate health-related quality-of-life (HRQoL) instruments. METHODS:
      MEDLINE from 1950, CINAHL from 1960, EMBASE from 1980, and PsycINFO from 1967, as
      well as additional sources were searched. The quality of the psychometric
      properties of the included instruments was evaluated by using the quality
      criteria for measurement properties of health status questionnaires. RESULTS: Ten
      studies that examined seven instruments were identified. The European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Biliary Cancer, the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire-Liver Metastases of Colorectal Cancer, the
      Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire, and the
      Quality of Life for Patients with Liver Cancer Instrument achieved satisfactory
      results in relation to the quality of their psychometric properties. CONCLUSION:
      Several well-validated instruments exist to adequately assess disease-specific
      HRQoL in patients with hepatobiliary or pancreatic cancers. Further improvement
      of the already-existing, promising measures is recommended.

PMID- 29057617
TI  - Biomolecule-Responsive Hydrogels in Medicine.
AB  - Recent advances and applications of biomolecule-responsive hydrogels, namely,
      glucose-responsive hydrogels, protein-responsive hydrogels, and nucleic-acid
      responsive hydrogels are highlighted. However, achieving the ultimate purpose of
      using biomolecule-responsive hydrogels in preclinical and clinical areas is still
      at the very early stage and calls for more novel designing concepts and advance
      ideas. On the way toward the real/clinical application of biomolecule-responsive
      hydrogels, plenty of factors should be extensively studied and examined under
      both in vitro and in vivo conditions. For example, biocompatibility,
      biointegration, and toxicity of biomolecule-responsive hydrogels should be
      carefully evaluated. From the living body's point of view, biocompatibility is
      seriously depended on the interactions at the tissue/polymer interface. These
      interactions are influenced by physical nature, chemical structure, surface
      properties, and degradation of the materials. In addition, the developments of
      advanced hydrogels with tunable biological and mechanical properties which cause
      no/low side effects are of great importance.

PMID- 29057618
TI  - Effects of 12 weeks of treatment with intravenously administered bococizumab, a
      humanized monoclonal antibody blocking proprotein convertase subtilisin/kexin
      type 9, in hypercholesterolemic subjects on high-dose statin.
AB  - AIMS: Two multiple-dose phase II studies were conducted in subjects with primary
      hypercholesterolemia to evaluate the LDL-C lowering efficacy, safety, and
      tolerability of bococizumab, a proprotein convertase subtilisin/kexin type 9
      (PCSK9) inhibitor. METHODS: The results from the two phase II, double-blinded,
      randomized, placebo-controlled, multicenter studies conducted in the USA and
      Canada were combined. In Study 1, 90 subjects with LDL-C >=100 mg/dL received
      intravenous (IV) placebo or bococizumab 0.25, 1, 3, or 6 mg/kg. In Study 2, 45
      subjects with LDL-C >=80 mg/dL received IV placebo or bococizumab 1 or 3 mg/kg.
      Subjects were treated every 4 weeks for 12 weeks. Dosing was interrupted if LDL-C
      dipped to <=25 mg/dL and resumed if LDL-C returned to >=40 mg/dL. The primary
      endpoint was percent LDL-C reduction from baseline at Week 12. RESULTS: At Week
      12, the reductions from baseline in LDL-C vs placebo in the bococizumab 0.25, 1,
      3, and 6 mg/kg groups were 9.3%, 10.2%, 41.6%, and 52.0%, respectively (P < .001
      vs placebo for all). LDL-C reductions were greater (69.9%) in subjects who
      received all three doses of bococizumab 6 mg/kg (P < .001 vs placebo).
      Pharmacogenomic analysis revealed that 15% of hyperlipidemic subjects carried
      polymorphisms associated with familial hypercholesterolemia, with maximal LDL-C
      reductions being similar between carriers and noncarriers. Adverse events were
      mild, unrelated to bococizumab, and resolved by Week 12. CONCLUSIONS: These
      studies demonstrated that bococizumab safely and effectively lowered LDL-C in
      hypercholesterolemic subjects on high doses of statin.

PMID- 29057619
TI  - Novel self-gelling injectable hydrogel/alpha-tricalcium phosphate composites for
      bone regeneration: Physiochemical and microcomputer tomographical
      characterization.
AB  - Mineralized hydrogels are increasingly gaining attention as biomaterials for bone
      regeneration. The most common mineralization strategy has been addition of
      preformed inorganic particles during hydrogel formation. This maintains
      injectability. One common form of bone cement is formed by mixing particles of
      the highly reactive calcium phosphate alpha-tricalcium phosphate (alpha-TCP) with
      water to form hydroxyapatite (HA). The calcium ions released during this reaction
      can be exploited to crosslink anionic, calcium-binding polymers such as the
      polysaccharide gellan gum (GG) to induce hydrogel formation. In this study, three
      different amounts of alpha-TCP particles were added to GG polymer solution to
      generate novel, injectable hydrogel-inorganic composites. Distribution of the
      inorganic phase in the hydrogel was studied by high resolution microcomputer
      tomography (uCT). Gelation occurred within 30 min. alpha-TCP converted to HA. uCT
      revealed inhomogeneous distribution of the inorganic phase in the composites.
      These results demonstrate the potential of the composites as alternatives to
      traditional alpha-TCP bone cement and pave the way for incorporation of
      biologically active substances and in vitro and in vivo testing. (c) 2017 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 822-828, 2018.

PMID- 29057620
TI  - The genetic and environmental architecture of substance use development from
      early adolescence into young adulthood: a longitudinal twin study of comorbidity
      of alcohol, tobacco and illicit drug use.
AB  - AIMS: To investigate how use of alcohol, illicit drugs and tobacco come from
      substance-specific pathways and from pathways general to all three substances
      through adolescent development. DESIGN: Analysis of population-based survey.
      Adolescent twins reported alcohol use (AU), tobacco use (TU) and illicit drug use
      (IDU) in three waves (2006, 2008, 2010). Restructuring data by age allowed for
      variance decomposition into age- and substance-specific and common genetic and
      environmental variance components. SETTING: Norway. PARTICIPANTS: Seven national
      twin birth cohorts from 1988 to 1994, totalling 1483 pairs (558 monozygotic; 925
      dizygotic, same and opposite sex). MEASUREMENTS: Six-point Likert scores of AU,
      TU and IDU on items from the Monitoring the Future Study. FINDINGS: Substance use
      was found to be highly heritable; a2  = 0.73 [95% confidence interval (CI) = 0.61
      0.94] for AU, a2  = 0.36 (CI = 0.18-0.52); d2  = 0.49 (95% CI = 0.29-0.62) for
      IDU and a2  = 0.46 (95% CI = 0.23-0.54); d2  = 0.05 (95% CI = 0.00-0.07) for TU
      during the whole adolescence period. General substance use (GSU) was also highly
      heritable at each age and averaged a2  = 0.57 (95% CI = 0.48-0.66). There was a
      high genetic carry-over from earlier age to later age. Genetic effects on GSU at
      ages 12-14 years were still detectable 4 years later. New substance (general and
      specific)-genetic effects also appeared. IDU demonstrated significant non
      additive genetic effects (ages 12-14 years). Shared environment had a small
      impact on AU only. There was almost no non-shared environmental carry-over from
      age to age, the effect probably due partly to reliability deficiency. Common
      genetic effects among substance and substance-specific genetic effects were
      observed at each age-period. CONCLUSIONS: Among Norwegian adolescents, there
      appear to be strong genetic effects on both substance-specific and comorbid use
      of alcohol, illicit drugs and tobacco; individual differences in alcohol use can
      be explained partially by family background.

PMID- 29057621
TI  - Regional economic impact assessment: Evaluating remedial alternatives for the
      Portland Harbor Superfund Site, Portland, Oregon, USA.
AB  - The present paper describes a methodology for evaluating impacts of Superfund
      remedial alternatives on the regional economy in the context of a broader
      sustainability evaluation. Although economic impact methodology is well
      established, some applications to Superfund remedial evaluation have created
      confusion because of seemingly contradictory results. This confusion arises from
      failure to be explicit about 2 opposing impacts of remediation expenditures: 1)
      positive regional impacts of spending additional money in the region and 2)
      negative regional impacts of the need to pay for the expenditures (and thus forgo
      other expenditures in the region). The present paper provides a template for
      economic impact assessment that takes both positive and negative impacts into
      account, thus providing comprehensive estimates of net impacts. The paper also
      provides a strategy for identifying and estimating major uncertainties in the net
      impacts. The recommended methodology was applied at the Portland Harbor Superfund
      Site, located along the Lower Willamette River in Portland, Oregon, USA. The US
      Environmental Protection Agency (USEPA) developed remedial alternatives that it
      estimated would cost up to several billion dollars, with construction durations
      possibly lasting decades. The economic study estimated regional economic impacts
      measured in terms of gross regional product (GRP), personal income, population,
      and employment-for 5 of the USEPA alternatives relative to the "no further
      action" alternative. Integr Environ Assess Manag 2018;14:32-42. (c) 2017 The
      Authors. Integrated Environmental Assessment and Management published by Wiley
      Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry
      (SETAC).

PMID- 29057622
TI  - Ligand-Controlled Electrodeposition of Highly Intrinsically Active and Optically
      Transparent NiFeOx Hy Film as a Water Oxidation Electrocatalyst.
AB  - A highly intrinsically active and optically transparent NiFeOx Hy water oxidation
      catalyst was prepared by electrodeposition of [Ni(C12 -tpen)](ClO4 )2 complex (Ni
      C12 ). This NiFeOx Hy film has a current density of 10 mA cm-2 with an
      overpotential (eta) of only 298 mV at nanomolar concentration and the current
      density of 10 mA cm-2 remains constant over 22 h in 1 m KOH. The extremely high
      turnover frequency of 0.51 s-1 was obtained with eta of 300 mV. More importantly,
      such outstanding activity and transparency (optical loss <0.5 %) of the NiFeOx Hy
      film are attributed to a ligand effect of the dodecyl substituent in Ni-C12 ,
      which enables its future application in solar water splitting.

PMID- 29057623
TI  - Microporous Cyclic Titanium-Oxo Clusters with Labile Surface Ligands.
AB  - By using ethylene glycol and monocarboxylic acid as surface ligands, a series of
      cyclic Ti-oxo clusters (CTOC) with permanent microporosity are successfully
      synthesized. With a cyclic {Ti32 O16 } backbone made of eight connected Ti4
      tetrahedral cages that are arranged in a zigzag fashion, the clusters have a
      "donut" shape with an inner diameter of 8.3 A, outer diameter of 26.9 A and
      height of 10.4 A. While both inner and outer walls of the "donut" clusters are
      modified by double-deprotonated ethylene glycolates, their upper and lower
      surfaces are bound by carboxylates and mono-deprotonated ethylene glycolates. The
      clusters are readily packed into one-dimensional tubes which are further arranged
      in two different modes into crystalline microporous solids with surface areas
      over 660 m2  g-1 , depending on the surface carboxylates. The solid with olefin
      bearing carboxylates exhibits a superior CO2 adsorption capacity of 40 cm3  g-1
      at 273 K under 1 atm. Moreover, the mono-deprotonated ethylene glycolates on the
      clusters are demonstrated to be highly exchangeable by other alcohols, providing
      a nice platform for creating microporous solids or films with a wide variety of
      surface functionalities.

PMID- 29057624
TI  - Grains in Selectively Grown MoS2 Thin Films.
AB  - Transition metal dichalcogenides (TMDCs) have recently been studied using various
      synthesis methods, such as chemical vapor deposition for large-scale production.
      Despite the realization of large-scale production with high material quality, a
      range of approaches have been made to solve the patterning issue of TMDCs
      focusing on the application of integrated devices; however, patterning is still
      under study to accurately represent nanoscale-sized patterns, as well as the
      desired positions and shapes. Here, an insulating substrate is treated
      selectively with O2 plasma, and MoS2 growth is induced in the superhydrophilic
      area. Selectively well-grown MoS2 patterns are confirmed by atomic force
      microscopy and Raman and photoluminescence spectroscopy. In addition, the grain
      size, according to the growth size, and grain boundary are analyzed by annual
      dark field transmission electron microscopy (TEM) and spherical aberration
      corrected scanning TEM to confirm the selective growth. An analysis of the device
      performance and the optical properties reveals an enhancement with increasing
      grain size. This method presents the path of the growth technique for patterning,
      as well as the direction that can be applied to devices and integrated circuits.

PMID- 29057626
TI  - IrIII -based Octahedral Metalloligands Derived Primitive Cubic Frameworks for
      Enhanced CO2 /N2 Separation.
AB  - We developed a metalloligand strategy to construct porous frameworks, viz. the
      combined use of IrIII -based octahedral metalloligands and the linear unit
      [Ni(cyclam)] easily afforded two isostructural complexes 1 and 2 with primitive
      cubic frameworks. Both complexes show good CO2 /N2 separation property.

PMID- 29057625
TI  - alpha2-glycine receptors modulate adult hippocampal neurogenesis and spatial
      memory.
AB  - The alpha2-glycine receptors (GlyRs) play important roles during early central
      nervous system development. However, these receptors' possible involvement in
      neurodevelopmental events occurring in the adult brain remains to be explored.
      Adult hippocampal neurogenesis (AHN) is the process by which new granule cell
      neurons are added to the dentate gyrus (DG) throughout adulthood. In this study,
      we observed that hippocampal adult neural stem cells (ANSCs) express alpha2
      containing GlyRs. Pharmacological inhibition of GlyRs by strychnine or picrotoxin
      decreased the proliferation of ANSCs, both in vivo and in vitro. Mice knockout
      for glra2, the gene coding for the GlyR alpha2 subunit, were determined to
      display impaired AHN, and this phenomenon was accompanied by deficits in spatial
      memory. These results, which reveal neurodevelopmental roles for alpha2-GlyRs in
      the adult brain, may be clinically relevant, given that a mutation in GLAR2, as
      well as AHN impairments, have been reported in autism spectrum disorder. (c) 2017
      Wiley Periodicals, Inc. Develop Neurobiol 77: 1430-1441, 2017.

PMID- 29057627
TI  - Genotype frequencies of human neutrophil antigen-3 in the Chinese Zhuang and Dong
      populations.
AB  - Individuals with the human neutrophil antigen (HNA)-3b/3b type can produce HNA-3a
      antibodies, which have been reported to cause severe, sometimes fatal transfusion
      related acute lung injury (TRALI). Our study aimed to determine the genotype
      frequency of HNA-3a/3b which will be helpful to estimate the potential risk for
      forming anti-HNA-3a, the clinically relevant antibody linked to TRALI in two
      different ethnic groups of southern China. Five hundred unrelated and healthy
      blood donors (284 male, 216 female; 300 Zhuangs, 200 Dongs) from the Guangxi
      Zhuang Autonomous Region were simultaneously typed for the HNA-3 allele using a
      polymerase chain reaction sequence-based typing (PCR-SBT) method. Genotype
      frequencies of HNA-3a/3a, HNA-3a/3b and HNA-3b/3b were 51.7%, 39.7% and 8.6% in
      the Zhuang population, and 44.0%, 49.0% and 7.0% in the Dong population,
      respectively. Homozygous HNA-3b/3b genotype frequency among the Zhuang population
      (8.6%) was significantly higher than previously reported in African Americans
      (0.4%), Brazilians (3.6%) and English Caucasians (2.9%) (p < .05). And the HNA
      3b/3b genotype frequency among the Dong population was higher than African
      Americans (0.4%) (p < .05). This study showed Chinese Zhuang and Dong populations
      possessed a higher frequency of HNA-3b/3b genotype, suggesting that they may be
      at greater risk for developing anti-HNA-3a alloantibodies that may cause severe
      cases of TRALI. A molecular-based identification of the HNA-3b/3b genotype in all
      multiparous female blood donors was suggested to reduce the risk of TRALI
      following plasma and whole blood allogeneic transfusions.

PMID- 29057628
TI  - Apraxia: Review and Update.
AB  - Praxis, the ability to perform skilled or learned movements is essential for
      daily living. Inability to perform such praxis movements is defined as apraxia.
      Apraxia can be further classified into subtypes such as ideomotor, ideational and
      limb-kinetic apraxia. Relevant brain regions have been found to include the
      motor, premotor, temporal and parietal cortices. Apraxia is found in a variety of
      highly prevalent neurological disorders including dementia, stroke and
      Parkinsonism. Furthermore, apraxia has been shown to negatively affect quality of
      life. Therefore, recognition and treatment of this disorder is critical. This
      article provides an overview of apraxia and highlights studies dealing with the
      neurophysiology of this disorder, opening up novel perspectives for the use of
      motor training and noninvasive brain stimulation as treatment.

PMID- 29057629
TI  - The Impacts of Influenza Infection and Vaccination on Exacerbation of Myasthenia
      Gravis.
AB  - BACKGROUND AND PURPOSE: Upper respiratory infection (URI), including influenza,
      may exacerbate the symptoms of myasthenia gravis (MG), which is an autoimmune
      disease that causes muscle weakness. There is also concern that the influenza
      vaccine may trigger or worsen autoimmune diseases. The objective of this study
      was to determine the impacts of influenza infection and vaccination on symptom
      severity in MG patients. METHODS: Patients diagnosed with MG were enrolled from
      10 university-affiliated hospitals between March and August 2015. Subjects
      completed a questionnaire at the first routine follow-up visit after enrolling in
      the study. The patient history was obtained to determine whether a URI had been
      experienced during the previous winter, if an influenza vaccination had been
      administered before the previous winter, and whether their MG symptoms were
      exacerbated during or following either a URI or vaccination. Influenza-like
      illness (ILI) was defined and differentiated from the common cold as a fever of
      >=38 degrees C accompanied by a cough and/or a sore throat. RESULTS: Of the 258
      enrolled patients [aged 54.1+/-15.2 years (mean+/-SD), 112 men, and 185 with
      generalized MG], 133 (51.6%) had received an influenza vaccination and 121
      (46.9%) had experienced a common cold (96 patients) or ILI (25 patients) during
      the analysis period. MG symptoms were aggravated in 10 (40%) patients after ILI,
      whereas only 2 (1.5%) experienced aggravation following influenza vaccination.
      The rate of symptom aggravation was significantly higher in patients experiencing
      an ILI (10/25, 40%) than in those with the common cold (15/96, 15.6%, p=0.006).
      CONCLUSIONS: The results of this study suggest that the potential risk of
      aggravating autoimmune disease is higher for ILI than for influenza vaccination,
      which further suggests that influenza vaccination can be offered to patients with
      MG.

PMID- 29057630
TI  - Femur Fractures in Parkinsonism: Analysis of a National Sample Cohort in South
      Korea.
AB  - BACKGROUND AND PURPOSE: Falling with a femur fracture is a serious event that
      negatively affects the quality of life of elderly individuals as well as patients
      with parkinsonism. This study investigated the association between parkinsonism
      and femur fracture and compared the risk of femur fracture between subjects with
      and without parkinsonism. METHODS: This study examined a population-based matched
      cohort constructed using the National Sample Cohort data set, which comprises
      approximately one million subscribers to medical insurance and aid in South
      Korea. Subjects with parkinsonism during 2003-2013 were identified as the exposed
      group, and up to five individuals matched for age, sex, and index years were
      identified as the controls for each parkinsonism subject. The risk of femur
      fracture for parkinsonism was evaluated using Cox regression. RESULTS: The
      incidence of femur fracture according to age, sex, and body mass index varied
      significantly between subjects with parkinsonism and controls (p<0.001). The
      presence of parkinsonism was associated with a higher risk of femur fractures for
      males [hazard ratio (HR)=2.85, 95% confidence interval [CI]=1.87-4.34], subjects
      younger than 65 years (HR=2.89, 95% CI=1.64-5.11), and underweight subjects
      (HR=3.90, 95% CI=1.82-8.35). The adjusted HR for femur fracture with parkinsonism
      was highest within 2 years of the disease diagnosis (HR=3.10, 95% CI=2.12-4.53).
      CONCLUSIONS: Our study found that the presence of parkinsonism is more strongly
      related to femur fracture in males, and increases the influence of traditional
      risk factors on femur fracture. It is necessary to consider how factors
      associated with the amount of ambulatory activity-even in an early diagnosed
      state-can play an important role in femur fracture in subjects with parkinsonism.

PMID- 29057631
TI  - Functional Connectivity of the Hippocampus in Early- and vs. Late-Onset
      Alzheimer's Disease.
AB  - BACKGROUND AND PURPOSE: Early-onset Alzheimer's disease (EOAD) and late-onset
      Alzheimer's disease (LOAD) have different clinical and neuroimaging
      characteristics, but memory decline is usually present in both types. However,
      there have been few functional studies focused on the hippocampus in Alzheimer's
      disease. We therefore investigated the functional connectivity between the
      hippocampus and other brain regions using resting-state fMRI and compared the
      findings between EOAD and LOAD. METHODS: We recruited 13 patients with EOAD and
      19 patients with LOAD at the early disease stage. Twenty-one young controls and
      ten old controls were also recruited. Each participant completed a standardized
      neuropsychological battery of tests and underwent T1-weighted structural MRI.
      fMRI data were acquired during the resting state using 3-T MRI. The functional
      connectivity to the hippocampus was calculated based on automated anatomical
      labeling templates. RESULTS: The functional connectivity from the hippocampus to
      other brain regions differed between patients with EOAD and LOAD. The LOAD
      patients showed decreased hippocampal connectivity to cortical regions, such as
      to the middle temporal cortex, orbitofrontal cortex, postcentral cortex,
      supramarginal cortex, and rolandic operculum. In contrast, EOAD patients showed
      smaller functional changes of the cortical regions connected to the hippocampus,
      such as the middle frontal cortex. CONCLUSIONS: EOAD and LOAD patients exhibited
      different hippocampal connectivity. The memory decline in EOAD may be due to
      brain areas other than the hippocampus.

PMID- 29057632
TI  - Effectiveness of Cognitive Behavioral Therapy for Caregivers of People with
      Dementia: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Caregivers endure tremendous physical, emotional, and
      financial burdens while caring for people with dementia. The current study aimed
      to estimate the effectiveness of cognitive behavioral therapy (CBT) for
      caregivers of people with dementia (CGPWD). METHODS: Studies in the MEDLINE,
      EMBASE, Cochrane Library, Web of Science, and SCOPUS databases were screened.
      Studies with a randomized controlled design and which produced CBT outcomes for
      CGPWD were included in this study, and we investigated these outcomes. RESULTS:
      The screening of abstracts of 263 studies resulted in 12 randomized controlled
      trials being included in this study. The mean age of the CGPWD ranged from 51.5
      to 66.2 years. The caregiver role was most frequently adopted by a female spouse
      or daughter. CBT for the CGPWD resulted in positive effects on various
      conditions, including depression, anxiety, stress, and dysfunctional thoughts.
      Depression was the most commonly evaluated condition, and the Center for
      Epidemiologic Studies Depression Scale (CES-D) was most frequently used as an
      inventory for depressive symptoms. The mean differences between the baseline and
      postintervention CES-D scores were compared between the CBT-intervention and
      control groups. The CES-D score decreased significantly more in the CBT
      intervention group than in the control group. The difference in pooled mean
      differences between the two groups was -4.98. CONCLUSIONS: CBT is an efficient
      intervention tool for reducing the various emotional burdens experienced by
      CGPWD. This meta-analysis found that CBT significantly improved the depressive
      symptoms of CGPWD.

PMID- 29057633
TI  - Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of
      Contracture.
AB  - BACKGROUND AND PURPOSE: The early diagnosis of LMNA-associated muscular dystrophy
      is important for preventing sudden arrest related to cardiac conduction block.
      However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with
      later involvement of contracture and limb-girdle muscular dystrophy type 1B is
      often delayed due to heterogeneous clinical presentations. We aimed to determine
      the clinical features that contribute to a delayed diagnosis. METHODS: We
      reviewed four patients who were recently diagnosed with LMNA-associated muscular
      dystrophy by targeted exome sequencing and who were initially diagnosed with
      nonspecific or other types of muscular dystrophy. RESULTS: Certain clinical
      features such as delayed contracture involvement and calf hypertrophy were found
      to contribute to a delayed diagnosis. Muscle biopsies were not informative for
      the diagnosis in these patients. CONCLUSIONS: Genetic testing of single or
      multiple genes is useful for confirming a diagnosis of LMNA-associated muscular
      dystrophy. Even EDMD patients could experience the later involvement of
      contracture, so clinicians should consider early genetic testing for patients
      with undiagnosed muscular dystrophy or laminopathy.

PMID- 29057635
TI  - Repetitive Questioning and Writing in a Patient with Transient Global Amnesia.

PMID- 29057634
TI  - A History of Falls is Associated with a Significant Increase in Acute Mortality
      in Women after Stroke.
AB  - BACKGROUND AND PURPOSE: The risks of falls and fractures increase after stroke.
      Little is known about the prognostic significance of previous falls and fractures
      after stroke. This study examined whether having a history of either event is
      associated with poststroke mortality. METHODS: We analyzed stroke register data
      collected prospectively between 2003 and 2015. Eight sex-specific models were
      analyzed, to which the following variables were incrementally added to examine
      their potential confounding effects: age, type of stroke, Oxfordshire Community
      Stroke Project classification, previous comorbidities, frailty as indicated by
      the prestroke modified Rankin Scale score, and acute illness parameters. Logistic
      regression was applied to investigate in-hospital and 30-day mortality, and Cox
      proportional-hazards models were applied to investigate longer-term outcomes of
      mortality. RESULTS: In total, 10,477 patients with stroke (86.1% ischemic) were
      included in the analysis. They were aged 77.7+/-11.9 years (mean+/-SD), and 52.2%
      were women. A history of falls was present in 8.6% of the men (n=430) and 20.2%
      of the women (n=1,105), while 3.8% (n=189) of the men and 12.9% of the women
      (n=706) had a history of both falls and fractures. Of the outcomes examined, a
      history of falls alone was associated with increased in-hospital mortality [odds
      ratio (OR)=1.33, 95% confidence interval (CI)=1.03-1.71] and 30-day mortality
      (OR=1.34, 95% CI=1.03-1.73) in women in the fully adjusted models. The Cox
      proportional-hazards models for longer-term outcomes and the history of falls and
      fractures combined showed no significant results. CONCLUSIONS: The history of
      falls is an important factor for acute stroke mortality in women. A previous
      history of falls may therefore be an important factor to consider in the short
      term stroke prognosis, particularly in women.

PMID- 29057636
TI  - A Novel GFAP Mutation in Late-Onset Alexander Disease Showing Diffusion
      Restriction.

PMID- 29057637
TI  - Guillain-Barre and Miller Fisher Overlap Syndrome Mimicking Alimentary Botulism.

PMID- 29057638
TI  - Erratum to: Prognosis of Patients with Behavioral Variant Frontotemporal Dementia
      Who have Focal Versus Diffuse Frontal Atrophy.
AB  - This corrects the article on p. 234 in vol. 13, PMID: 28748674.

PMID- 29057639
TI  - Erratum to: Severe Paraneoplastic Parkinsonism: A Rare Cause Revealing Breast
      Cancer.
AB  - This corrects the article on p. 310 in vol. 13, PMID: 28748681.

PMID- 29057640
TI  - The ARMOUR Study: Anti-VEGF in Neovascular AMD--Our Understanding in a Real-World
      Indian Setting.
AB  - PURPOSE: The aim of our study was to share our experience with anti-vascular
      endothelial growth factor (anti-VEGF) injections in the treatment of neovascular
      age-related macular degeneration (nAMD) in a real-world setting. DESIGN: A
      retrospective, observational study. METHODS: Patients of Indian origin with nAMD
      receiving anti-VEGF with a minimum follow-up of 12 months were enrolled in this
      study. In group 1, patients were treated on a pro re nata (PRN) basis; in group
      2, patients received a loading dose (3 injecti Results: Overall, we observed that
      77.31% (92/119 eyes) of patients either maintained or had improved visual acuity
      at 12 months' follow-up. Similar visual outcome was observed in both groups. The
      average number of injections given in group 1 was 4.98 and in group 2 was 3.7.
      CDVA at 12 months was significantly correlated with type of drug molecule, CSFT
      at 3 and 12 months, baseline visual acuity, and CDVA at 3 months. CONCLUSIONS:
      PRN treatment with significantly fewer injections achieved similar anatomical and
      functional outcomes when compared with the loading dose group. The results of
      this study need to be validated with a larger study group and a longer follow-up.

PMID- 29057641
TI  - Anti-Vascular Endothelial Growth Factor Therapy for Myopic Choroidal
      Neovascularization.
AB  - Myopic choroidal neovascularization (CNV) is one of the most vision-impairing
      complications in patients with pathologic myopia. It is also one of the most
      frequently encountered non.age-related macular degeneration causes of CNV and
      affects young patients in the working age group. Fluorescein angiography (FA) and
      spectral domain optical coherence tomography (OCT) are generally indicated to
      confirm the diagnosis of active myopic CNV before initiation of treatment.
      Without treatment, natural history studies have shown that the vision outcome can
      be very poor. More recently, a number of retrospective, prospective and phase 3,
      multicenter, randomized controlled trials have established the safety and
      efficacy of intravitreal anti.vascular endothelial growth factor (VEGF) agents
      for the treatment of myopic CNV. Long-term follow-up studies have found that some
      of the initial vision gained after intravitreal anti-VEGF therapy may not be
      maintained, owing to the presence and progression of chorioretinal atrophy (CRA)
      adjacent to the CNV. Further research on clinical and imaging characteristics may
      elucidate the prognostic factors that are crucial to optimizing the treatment and
      prevention of visual impairment associated with myopic CNV.

PMID- 29057642
TI  - Insulin therapy for adult patients with type 2 diabetes mellitus: a position
      statement of the Korean Diabetes Association, 2017.
AB  - The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice
      Guidelines. In 2017, the KDA published a position statement on the use of
      antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM).
      Growing evidence from new multinational clinical trials using novel and
      traditional insulin analogues has also been accumulated. Following global trends,
      many results of clinical trials, especially concerning the clinical efficacy and
      safety of insulin therapy, have been published about Korean patients with T2DM.
      After a systematic search of recent evidence, the KDA updated and modified its
      clinical practice recommendations regarding the initiation, choice, and
      intensification of insulin and created an insulin treatment algorithm for the
      first time to guide physicians caring for adult Korean patients with T2DM.

PMID- 29057644
TI  - Ultradispersed and Single-Layered MoS2 Nanoflakes Strongly Coupled with Graphene:
      An Optimized Structure with High Kinetics for the Hydrogen Evolution Reaction.
AB  - As one of the most promising Pt alternatives for cost-effective hydrogen
      production, molybdenum disulfide (MoS2), although has been studied extensively to
      improve its electrocatalytic activity, suffers from scarce active sites, low
      conductivity, and lack of interaction with substrates. To this end, we anchor
      ultradispersed and single-layered MoS2 nanoflakes on graphene sheets via a hybrid
      intermediate (MoOx-cysteine-graphene oxide), which not only confines the
      subsequent growth of MoS2 on the graphene surface but also ensures the intimate
      interaction between Mo species and graphene at the initial stage. Mo-O-C bond and
      a possible residual MoO3-x layer are proposed to comprise the interface bridging
      the two inherent incompatible phases, MoS2 and graphene. This strongly coupled
      structure together with the highly exposed MoS2 morphology accelerates the
      electron injection from graphene to the active sites of MoS2, and thus the
      hydrogen evolution reaction (HER) can achieve an overpotential of ~275 mV at ~
      740 mA cm-2, and a Pt-like Tafel slope of ~35 mV dec-1. Our results shed light on
      the indispensable role of interfacial interaction within semiconducting material
      nanocarbon composites and provide a new insight into the actual activity of MoS2
      toward the HER.

PMID- 29057643
TI  - Monotherapy in patients with type 2 diabetes mellitus.
AB  - In order to improve the quality of life and to prevent chronic complications
      related to diabetes mellitus, intensive lifestyle modification and proper
      medication are needed from the early stage of diagnosis of type 2 diabetes
      mellitus (T2DM). When using the first medication for diabetic patients, the
      appropriate treatment should be selected considering the clinical characteristics
      of the patient, efficacy of the drug, side effects, and cost. In general, the use
      of metformin as the first treatment for oral hypoglycemic monotherapy is
      recommended because of its excellent blood glucose-lowering effect, relatively
      low side effects, long-term proven safety, low risk of hypoglycemia, and low
      weight gain. If metformin is difficult to use as a first-line treatment, other
      appropriate medications should be selected in view of the clinical situation. If
      the goal of achieving glycemic control is not achieved by monotherapy, a
      combination therapy with different mechanisms of action should be initiated
      promptly.

PMID- 29057645
TI  - Exchange Bias Effect and Orbital Reconstruction in (001)-Oriented LaMnO3/LaNiO3
      Superlattices.
AB  - Paramagnetic LaNiO3 (LNO)-based heterostructures have been attracting the
      attention of researches, especially since the interesting exchange bias (EB)
      effect has been observed in (111)-oriented LaMnO3 (LMO)/LNO superlattices (SLs).
      However, this effect is not expected to occur in the (001) direction SLs. In this
      paper, we report the observation of an unexpected EB effect in (001)-oriented
      (LMO)3/(LNO)t SLs. The orbits of interfacial Mn/Ni ions preferentially occupy the
      strain-stabilized x2 - y2 in ultrathin LNO layers [t <= 4 unit cells (u.c.)].
      Conversely, as the LNO layer becomes thicker (t >= 6 u.c.), the EB effect is
      absent, and the orbits are reconstructed to form the 3z2 - r2 preferential
      occupancy. The absence of the EB in thicker LNO-based SLs is attributed to the
      interfacial charge transfer suppressed by orbital reconstruction as a consequence
      of the increasing LNO thickness. In the thinner LNO-based SLs, the larger charge
      transfer results in stronger localized magnetic moments for the cause of the EB
      effect. These results provide a useful interpretation of the relationship between
      macroscopic magnetic properties and the microscopic electronic structure in oxide
      based heterostructures.

PMID- 29057646
TI  - Effect of Donor Building Blocks on the Charge-Transfer Characteristics of
      Diketopyrrolopyrrole-Based Donor-Acceptor-Type Semiconducting Copolymers.
AB  - We investigate the effect of donor (D) building blocks on the charge
      transportation characteristics of donor (D)-acceptor (A)-type semiconducting
      copolymers with alternating electron-donating and electron-accepting units to
      provide a basis for the rational design of high-performance semiconducting
      polymers. For this purpose, we studied three different diketopyrrolopyrrole (DPP)
      based semiconducting copolymers comprising a common dithienyl-DPP [3,6-dithienyl
      2,5-diketopyrrolo(3,4-c)pyrrole] and variable donor moieties: phenylene (P)
      PDPPTPT, thiophene (T)-PDPP3T, and thienothiophene (TT)-PDPP2T-TT. Structural
      analysis using grazing incidence X-ray diffraction indicates that all three DPP
      based copolymer films have edge-on phases but poor crystallinity of the films,
      except the PDPP2T-TT copolymer with branched alkyl side chains that are
      relatively long. The electrical measurements show that the DPP-based copolymer
      with a TT donor unit has the highest field-effect mobility value of 0.30 cm2/V s.
      To understand the role of the donor units in DPP-based D-A copolymers, further
      insight into the charge transportation behavior is realized by analyzing the
      temperature-dependent transfer curves of the DPP semiconducting copolymer-based
      field-effect transistors using the Gaussian disorder model. Compared to the DPP
      based D-A-type semiconducting copolymer with a P-moiety and shorter-branched
      alkyl side chains that exhibit a broad distribution in the density of localized
      states (DOS) and a higher thermal-activated energy for charge hopping, the DPP
      copolymers with a TT-moiety and longer branched side chains have the narrowest
      DOS, the lowest activation energy, and thus the highest hole mobility. These
      results suggest that the higher mobilities obtained from PDPP2T-TT with a TT
      donor unit can be attributed to the suppressed DOS distribution near the
      transport level, which mainly originates from the narrowest energy band gap tuned
      with the orbital couplings of the DPP acceptor and TT donor units.

PMID- 29057647
TI  - Adsorption Thermodynamic Analysis of a Quartz Tuning Fork Based Sensor for
      Volatile Organic Compounds Detection.
AB  - A volatile organic compounds (VOC) sensor based on molecularly imprinted polymer
      (MIP) modified quartz tuning fork (QTF) has been developed. In this paper, the
      stability of the modified sensor as a function of the MIP composition, and the
      temperature effect of the analyte adsorption on the sensing transduction
      mechanism are evaluated. By mixing MIP and PS together, the stability was
      improved. A target analyte, o-xylene, was chosen as the VOC model to study the
      sensor response in a temperature range of 6-40  degrees C. Langmuir model fitted
      adsorption isotherms were used for thermodynamic analysis. The changes in the
      sensitivity of the QTF sensor to temperature rendered different behaviors. For a
      freshly modified QTF sensor, the adsorption response increased with increasing
      temperature, while for an aged QTF sensor, the adsorption response decreased with
      increasing temperature. The results indicated that the enthalpy change of the MIP
      and PS composition sensing material changes from positive to negative over the
      course of aging. The characterization of the reaction enabled the definition of
      sensor calibration conditions and stable sensor performance in field testing
      conditions.

PMID- 29057648
TI  - Long-Term Stability of Oxide Nanowire Sensors via Heavily Doped Oxide Contact.
AB  - Long-term stability of a chemical sensor is an essential quality for long-term
      collection of data related to exhaled breath, environmental air, and other
      sources in the Internet of things (IoT) era. Although an oxide nanowire sensor
      has shown great potential as a chemical sensor, the long-term stability of
      sensitivity has not been realized yet due to electrical degradation under harsh
      sensing conditions. Here, we report a rational concept to accomplish long-term
      electrical stability of metal oxide nanowire sensors via introduction of a
      heavily doped metal oxide contact layer. Antimony-doped SnO2 (ATO) contacts on
      SnO2 nanowires show much more stable and lower electrical contact resistance than
      conventional Ti contacts for high temperature (200  degrees C) conditions, which
      are required to operate chemical sensors. The stable and low contact resistance
      of ATO was confirmed for at least 1960 h under 200  degrees C in open air. This
      heavily doped oxide contact enables us to realize the long-term stability of SnO2
      nanowire sensors while maintaining the sensitivity for both NO2 gas and light
      (photo) detections. The applicability of our method is confirmed for sensors on a
      flexible polyethylene naphthalate (PEN) substrate. Since the proposed fundamental
      concept can be applied to various oxide nanostructures, it will give a foundation
      for designing long-term stable oxide nanomaterial-based IoT sensors.

PMID- 29057649
TI  - Optimized Method to Quantify Dopamine Turnover in the Mammalian Retina.
AB  - Measurement of dopamine (DA) release in the retina allows the interrogation of
      the complex neural circuits within this tissue. A number of previous methods have
      been used to quantify this neuromodulator, the most common of which is HPLC with
      electrochemical detection (HPLC-ECD). However, this technique can produce
      significant concentration uncertainties. In this present study, we report a
      sensitive and accurate UHPLC-MS/MS method for the quantification of DA and its
      primary metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in mouse retina.
      Internal standards DA-d4 and DOPAC-d5 result in standard curve linearity for DA
      from 0.05-100 ng/mL (LOD = 6 pg/mL) and DOPAC from 0.5-100 ng/mL (LOD = 162
      pg/mL). A systematic study of tissue extraction conditions reveals that the use
      of formic acid (1%), in place of the more commonly used perchloric acid, combined
      with 0.5 mM ascorbic acid prevents significant oxidation of the analytes. When
      the method is applied to mouse retinae a significant increase in the DOPAC/DA
      ratio is observed following in vivo light stimulation. We additionally examined
      the effect of anesthesia on DA and DOPAC levels in the retina in vivo and find
      that basal dark-adapted concentrations are not affected. Light caused a similar
      increase in DOPAC/DA ratio but interindividual variation was significantly
      reduced. Together, we systematically describe the ideal conditions to accurately
      and reliably measure DA turnover in the mammalian retina.

PMID- 29057650
TI  - Molecular Spur Gears Based on a Switchable Quinquepyridine Foldamer Acting as a
      Stator.
AB  - Two triptycene rotators have been covalently linked to the backbone of a
      quinquepyridine (QPY) foldamer at the second and fourth pyridine rings,
      respectively, to form molecular spur gears. The studies revealed that a QPY
      foldamer as a stator can reversibly control the intermeshed and demeshed states
      of molecular spur gears due to the linear-to-helical conformational switching
      triggered by complexation/decomplexation.

PMID- 29057651
TI  - MethylQuant: A Tool for Sensitive Validation of Enzyme-Mediated Protein
      Methylation Sites from Heavy-Methyl SILAC Data.
AB  - The study of post-translational methylation is hampered by the fact that large
      scale LC-MS/MS experiments produce high methylpeptide false discovery rates
      (FDRs). The use of heavy-methyl stable isotope labeling by amino acids in cell
      culture (heavy-methyl SILAC) can drastically reduce these FDRs; however, this
      approach is limited by a lack of heavy-methyl SILAC compatible software. To fill
      this gap, we recently developed MethylQuant. Here, using an updated version of
      MethylQuant, we demonstrate its methylpeptide validation and quantification
      capabilities and provide guidelines for its best use. Using reference heavy
      methyl SILAC data sets, we show that MethylQuant predicts with statistical
      significance the true or false positive status of methylpeptides in samples of
      varying complexity, degree of methylpeptide enrichment, and heavy to light mixing
      ratios. We introduce methylpeptide confidence indicators, MethylQuant Confidence
      and MethylQuant Score, and demonstrate their strong performance in complex
      samples characterized by a lack of methylpeptide enrichment. For these
      challenging data sets, MethylQuant identifies 882 of 1165 true positive
      methylpeptide spectrum matches (i.e., >75% sensitivity) at high specificity (<2%
      FDR) and achieves near-perfect specificity at 41% sensitivity. We also
      demonstrate that MethylQuant produces high accuracy relative quantification data
      that are tolerant of interference from coeluting peptide ions. Together
      MethylQuant's capabilities provide a path toward routine, accurate
      characterizations of the methylproteome using heavy-methyl SILAC.

PMID- 29057652
TI  - Amorphous Co2B Grown on CoSe2 Nanosheets as a Hybrid Catalyst for Efficient
      Overall Water Splitting in Alkaline Medium.
AB  - In this work, we synthesized a novel hybrid catalyst (Co2B/CoSe2) by growing
      amorphous Co2B on the surface of CoSe2 nanosheets. Benefiting from the prominent
      coupled effects between Co2B and CoSe2 nanosheets, an efficient oxygen evolution
      reaction catalyst Co2B/CoSe2 exhibits a very low overpotential of 320 mV @ 10 mA
      cm-2 with a Tafel slope of 56.0 mV dec-1 in alkaline medium. An overpotential of
      300 mV can also be achieved by Co2B/CoSe2 at the same condition for hydrogen
      evolution reaction. Notably, at the applied potential of 1.73 V, the
      electrocatalyst Co2B/CoSe2 demonstrates a current density of 10 mA cm-2 for
      overall water splitting and displays an outstanding long-term stability. The
      faradaic efficiencies of Co2B/CoSe2 for both hydrogen and oxygen evolution are
      close to 100%.

PMID- 29057653
TI  - Mitochondrion-Targeting, Environment-Sensitive Red Fluorescent Probe for Highly
      Sensitive Detection and Imaging of Vicinal Dithiol-Containing Proteins.
AB  - Mitochondrial vicinal dithiol-containing proteins (VDPs) are key regulators in
      cellular redox homeostasis and useful markers for diagnostics of redox-dependent
      diseases. Current probes fail to target mitochondrial VDPs and show limited
      sensitivity and response rate. We develop a novel fluorescent probe using an
      engineered benzoxadiazole fluorophore that allows selective targeting of
      mitochondria and exhibits highly sensitive environment responsiveness. This probe
      is almost nonfluorescent in aqueous media, while delivering intense fluorescence
      upon binding to VDPs via a cyclic dithiaarsane ligand. The fluorescence probe is
      shown to have rapid response within 30 s and high sensitivity for detecting
      reduced bovine serum albumin (rBSA) in the concentration range from 0 to 0.1 MUM
      with a detection limit of 2 nM. To our knowledge, this is the first fluorescence
      probe for VDPs which exhibits deep red emission, instantaneous response, high
      turn-on fluorescence ratio, and specific mitochondrial localization. It may
      provide a new tool for in situ monitoring mitochondrial VDPs.

PMID- 29057654
TI  - Comparing the Aggregation Free Energy Landscapes of Amyloid Beta(1-42) and
      Amyloid Beta(1-40).
AB  - Using a predictive coarse-grained protein force field, we compute and compare the
      free energy landscapes and relative stabilities of amyloid-beta protein (1-42)
      and amyloid-beta protein (1-40) in their monomeric and oligomeric forms up to the
      octamer. At the same concentration, the aggregation free energy profile of
      Abeta42 is more downhill, with a computed solubility that is about 10 times
      smaller than that of Abeta40. At a concentration of 40 MUM, the clear free energy
      barrier between the pre-fibrillar tetramer form and the fibrillar pentamer in the
      Abeta40 aggregation landscape disappears for Abeta42, suggesting that the Abeta42
      tetramer has a more diverse structural range. To further compare the landscapes,
      we develop a cluster analysis based on the structural similarity between
      configurations and use it to construct an oligomerization map that captures the
      paths of easy interconversion between different but structurally similar states
      of oligomers for both species. A taxonomy of the oligomer species based on beta
      sheet stacking topologies is proposed. The comparison of the two oligomerization
      maps highlights several key differences in the landscapes that can be attributed
      to the two additional C-terminal residues that Abeta40 lacks. In general, the two
      terminal residues strongly stabilize the oligomeric structures for Abeta42
      relative to Abeta40, and greatly facilitate the conversion from pre-fibrillar
      trimers to fibrillar tetramers.

PMID- 29057655
TI  - Spiro-Fused Perylene Diimide Arrays.
AB  - The straightforward palladium-catalyzed synthesis protocol toward spiro-fused
      perylene diimides is developed. The reaction involves two palladium-catalyzed C-H
      activations and 4-fold C-C bond formation sequence from readily available
      precursors. This facile and step-economic approach also provides another
      convenient access to ethylene-bridged dimer (NDP) and further pi-extended spiro
      system (SNTP). In addition, the molecular structure of spirodiperylenetetraimide
      (SDP) is illustrated to show a three-dimensional (3D) cruciform configuration,
      and its absorbance is distinctly red-shifted due to the significant
      spiroconjugation effect. With combined properties of broadened and intensive
      absorption, aligned LUMO levels, and unique molecular geometry, the spiro-fused
      PDI system represents a new kind of high-performance semiconducting framework as
      the electron acceptor in high-efficiency organic solar cells.

PMID- 29057656
TI  - Unraveling the Charge Extraction Mechanism of Perovskite Solar Cells Fabricated
      with Two-Step Spin Coating: Interfacial Energetics between Methylammonium Lead
      Iodide and C60.
AB  - In organolead halide perovskite solar cells (PSCs), interfacial properties
      between the perovskite and charge transport layers are the critical factors
      governing charge extraction efficiency. In this study, the effect of interfacial
      energetics between two-step spin-coated methylammonium lead iodide (MAPbI3) with
      different methylammonium iodide (MAI) concentrations and C60 on the charge
      extraction efficiency is investigated. The electronic structures of perovskite
      films are significantly varied by the MAI concentrations due to the changes in
      the residual precursor and MA+ defect content. As compared to the optimum PSCs
      with 25 mg mL-1 MAI, PSCs with other MAI concentrations show significantly lower
      power conversion efficiencies and severe hysteresis. The energy level alignment
      at the C60/MAPbI3 interface determined by ultraviolet and inverse photoelectron
      spectroscopy measurements reveals the origin of distinct differences in device
      performances. The conduction band offset at the C60/MAPbI3 interface plays a
      crucial role in efficient charge extraction in PSCs.

PMID- 29057657
TI  - Investigation of Heterogeneous Painted Systems by Micro-Spatially Offset Raman
      Spectroscopy.
AB  - A recently developed technique of Micro-Spatially Offset Raman Spectroscopy
      (micro-SORS) extends the applicability of Raman spectroscopy to probing thin,
      highly diffusely scattering layers such as stratified paint samples, enabling
      their nondestructive chemical characterization. The technique has a wide
      applicability across areas such as cultural heritage, polymer research,
      forensics, and biological fields; however, currently, it suffers from a major
      unaddressed issue related to its ineffectiveness with highly heterogeneous
      samples. In this paper, we address this unmet need while demonstrating an
      effective strategy to probe such samples, involving a mapping on scales
      substantially larger than the scale of heterogeneity. This approach provides an
      effective means of obtaining robust and representative micro-SORS datasets from
      which sample composition can be effectively deduced, even in these extreme
      scenarios. The approach is compared with a basic point collection approach on two
      layer paint systems where different layers-top, bottom, or both-are
      heterogeneous. The study has particular relevance to cultural heritage, where
      heterogeneous layers are often encountered with painted stratigraphies.

PMID- 29057658
TI  - PhoStar: Identifying Tandem Mass Spectra of Phosphorylated Peptides before
      Database Search.
AB  - Standard proteomics workflows use tandem mass spectrometry followed by sequence
      database search to analyze complex biological samples. The identification of
      proteins carrying post-translational modifications, for example, phosphorylation,
      is typically addressed by allowing variable modifications in the searched
      sequences. Accounting for these variations exponentially increases the
      combinatorial space in the database, which leads to increased processing times
      and more false positive identifications. The here-presented tool PhoStar
      identifies spectra that originate from phosphorylated peptides before database
      search using a supervised machine learning approach. The model for the prediction
      of phosphorylation was trained and validated with an accuracy of 97.6% on a large
      set of high-confidence spectra collected from publicly available experimental
      data. Its power was further validated by predicting phosphorylation in the
      complete NIST human and mouse high collision-dissociation spectral libraries,
      achieving an accuracy of 98.2 and 97.9%, respectively. We demonstrate the
      application of PhoStar by using it for spectra filtering before database search.
      In database search of HeLa samples the peptide search space was reduced by 27-66%
      while finding at least 97% of total peptide identifications (at 1% FDR) compared
      with a standard workflow.

PMID- 29057659
TI  - Giant Vesicles with Anchored Tiny Gold Nanowires: Fabrication and Surface
      Enhanced Raman Scattering.
AB  - Sensitivity and reproducibility are two major concerns to improve the performance
      and extend the range of practical applications of surface-enhanced Raman
      scattering (SERS). A theoretical report reveals that hot spots formed by gold
      nanoparticles with a tip-to-tip configuration would generate the maximum electric
      field enhancement because of the lightning rod effect. In our present study, we
      constructed a giant vesicle consisting of anchored tiny gold nanowires to provide
      a high density of sharp tip-to-tip nanogaps for SERS application. The tiny gold
      nanowires were directly grown and anchored onto the surfaces of polystyrene (PS)
      microspheres by a seed-mediated method. Then, the removal of PS microspheres by
      tetrahydrofuran led to the formation of the giant gold vesicles with hierarchical
      cage structures, providing the sharp tips and high density of hot spots for
      improving SERS performance. Compared with the nonwire structure (island and
      inhibited nanoparticle), giant gold vesicles with tiny wires showed a higher SERS
      enhancement factor (9.90 * 107) and quantitative SERS analysis in the range of 10
      4 to 10-7 M. In addition, the large-scale giant gold vesicle array on the silica
      substrate resulted in a high reproducibility of SERS signals with the variation
      of intensities less than 7.6%.

PMID- 29057660
TI  - Stroke Administrative Severity Index: using administrative data for 30-day
      poststroke outcomes prediction.
AB  - AIM: Current stroke severity scales cannot be used for archival data. We develop
      and validate a measure of stroke severity at hospital discharge (Stroke
      Administrative Severity Index [SASI]) for use in billing data. METHODS: We used
      the NIH Stroke Scale (NIHSS) as the theoretical framework and identified 285
      relevant International Classification of Diseases, 9th Revision diagnosis and
      procedure codes, grouping them into 23 indicator variables using cluster
      analysis. A 60% sample of stroke patients in Medicare data were used for modeling
      risk of 30-day postdischarge mortality or discharge to hospice, with validation
      performed on the remaining 40% and on data with NIHSS scores. RESULTS: Model fit
      was good (p > 0.05) and concordance was strong (C-statistic = 0.76-0.83). The
      SASI predicted NIHSS at discharge (C = 0.83). CONCLUSION: The SASI model and
      score provide important tools to control for stroke severity at time of hospital
      discharge. It can be used as a risk-adjustment variable in administrative data
      analyses to measure postdischarge outcomes.

PMID- 29057661
TI  - The effect of zinc and melatonin supplementation on immunity parameters in breast
      cancer induced by DMBA in rats.
AB  - OBJECTIVE: The aim of the study was to determine the effects of zinc and
      melatonin supplements on the immunity parameters of female rats with breast
      cancer induced by DMBA. METHODS: Group 1; Control, Group 2; 7,12
      dimethylbenz[a]anthracene (DMBA), Group 3; DMBA + zinc, Group 4; DMBA +
      melatonin, Group 5; DMBA + zinc + melatonin. The rats' breast cancer was induced
      by DMBA 80 mg/kg. Groups 3-5 received daily 5 mg/kg doses of zinc, melatonin, and
      zinc + melatonin, respectively. Lymphocyte rates, T-lymphocyte subgroups, B
      lymphocyte and natural killer cells (NK), and natural killer T (NKT) were
      evaluated. RESULTS: The most significant increase in lymphocyte, T-lymphocyte,
      and CD4 lymphocyte rates was found in Group 5. The highest NKT cell rates were
      found in Group 3. CONCLUSIONS: Findings show that zinc and melatonin supplements
      have led to an increase in the immunity parameters of rats with breast cancer.

PMID- 29057662
TI  - Biomarkers of propofol metabolism in neonates: the quest beyond ontogeny.

PMID- 29057663
TI  - Gene therapy for inherited retinal and optic nerve degenerations.
AB  - INTRODUCTION: The eye is a target for investigational gene therapy due to the
      monogenic nature of many inherited retinal and optic nerve degenerations (IRD),
      its accessibility, tight blood-ocular barrier, the ability to non-invasively
      monitor for functional and anatomic outcomes, as well as its relative immune
      privileged state.Vectors currently used in IRD clinical trials include adeno
      associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA
      viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV
      are non-integrating, while lentivirus integrate into the host cell genome, and
      have a larger transgene capacity. Areas covered: This review covers Leber's
      congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome,
      Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X
      linked retinoschisis. Expert opinion: Despite great potential, gene therapy for
      IRD raises many questions, including the potential for less invasive intravitreal
      versus subretinal delivery, efficacy, safety, and longevity of response, as well
      as acceptance of novel study endpoints by regulatory bodies, patients,
      clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will
      require widespread genetic screening to identify and diagnose patients based on
      genotype instead of phenotype.

PMID- 29057664
TI  - Clinical and pharmaceutical success from discovery to regulatory approval:
      biomarkers, modeling and analytical technologies.
AB  - The 8th Annual Shanghai Symposium on Clinical and Pharmaceutical Solutions
      through Analysis (CPSA): Clinical and Pharmaceutical Success from Discovery to
      Regulatory Approval: Biomarkers, Modeling and Analytical Technologies (CPSA
      Shanghai 2017); Renaissance Shanghai Pudong Hotel, Shanghai, China, 12-14 April
      2017 was held on 12-14 April 2017 in Shanghai, China. The meeting was featured
      with highly interactive events including diversified symposia, workshops,
      roundtable discussions, conference awards and poster sessions. There were over
      220 participants with 61 oral presentations and 20 posters presented. In
      addition, the meeting included a preconference workshop with an inaugural session
      on the evaluation of quality and efficacy for generic drugs in China.

PMID- 29057667
TI  - No increased death toll for long-term menopausal hormone therapy.
AB  - It took many years since the initial publication of data from the Women's Health
      Initiative (WHI) study until further analyses and additional accumulated clinical
      information allowed realization of the full scope of its results. At first, the
      focus was on morbidity, mainly the slightly higher incidence of cardiovascular
      events and breast cancer cases among postmenopausal hormone users. Then, the age
      factor became evident, and the good safety profile of hormone therapy in healthy
      women initiating treatment near menopause and using it for up to 10 years eased
      the previous concerns. Now, 15 years after the first release of the WHI data,
      long-term follow-up of the WHI cohort enables consideration of mortality records
      as well. These data were recently summarized by the WHI investigators as follows:
      'Among postmenopausal women, hormone therapy with CEE plus MPA for a median of
      5.6 years or with CEE alone for a median of 7.2 years was not associated with
      risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow
      up of 18 years.' It seems that the bitter debate on the hazards of postmenopausal
      hormone therapy has come to an end, since the existing database permits clear and
      rationalized prescribing decisions.

PMID- 29057666
TI  - Granisetron: a review of pharmacokinetics and clinical experience in chemotherapy
      induced - nausea and vomiting.
AB  - INTRODUCTION: Chemotherapy induced nausea and vomiting (CINV) are major side
      effects of chemotherapy and a great burden to patients' quality of life.
      Serotonin and substance P are the major neurotransmitters involved in the
      pathophysiology of CINV, but in spite of new antiemetics no completely effective
      regime exists for its prevention or treatment. Areas covered: In this review the
      authors provide a detailed description of granisetron's chemistry
      pharmacokinetics, pharmacodynamics, toxicity and a brief review of clinical
      trials involving granisetron and the management of CINV. We searched reviews,
      meta-analysis and randomized controlled trials (Medline, Embase and article
      reference lists). Expert opinion: According to current literature, granisetron 2
      mg orally or 0,01mg/kg (1 mg) intravenously per day, co-administered with
      dexamethasone and NK-1 antagonists is the recommended regime for highly
      emetogenic chemotherapy. In the future the role of transdermal and subcutaneous
      formulations against delayed CINV will be clarified and probably enhance
      patients' convenience.

PMID- 29057668
TI  - Modeling subjective well-being in individuals with chronic pain and a physical
      disability: the role of pain control and pain catastrophizing.
AB  - PURPOSE: To investigate the associations between subjective well-being and pain
      intensity, pain interference, and depression in individuals with physical
      disabilities. We hypothesized that (1) pain control and (2) pain catastrophizing
      mediate the effects of subjective well-being on pain intensity, pain
      interference, and depression. METHODS: Analyses of cross-sectional data from 96
      individuals diagnosed with spinal cord injury, multiple sclerosis, neuromuscular
      disease, or post-polio syndrome, with average pain intensity of >=4 (0-10) on at
      least half the days in the past month. Two models tested study hypotheses using
      structural equation. RESULTS: Both models showed acceptable model fit. Pain
      catastrophizing significantly mediated the effect of subjective well-being on
      pain intensity and pain interference, but not on depression. Pain control did not
      significantly mediate the effect of subjective well-being on pain intensity, pain
      interference, or depression. Path coefficients showed significant direct effects
      of subjective well-being on pain control (beta = 0.39), pain catastrophizing
      (beta = -0.61), pain interference (beta = -0.48; -0.42), and depression (beta = 
      0.75; -0.78). CONCLUSIONS: This study supports the potential of enhancing
      subjective well-being and lowering pain catastrophizing for reducing pain
      intensity, pain interference, and depressive symptoms in individuals with chronic
      pain and a physical disability. The findings indicate that true experiments to
      test for causal associations are warranted. Implications for rehabilitation The
      majority of individuals with physical disabilities report having persistent
      moderate-to-severe pain that may negatively limit daily activities and quality of
      life. The present cross-sectional study indicates that individuals who reported
      greater subjective well-being showed significantly lower pain intensity via the
      mediating effect of lower pain catastrophizing. Since sample size and respective
      power are low, these findings should be taken as first indications of potential
      underlying mechanisms between subjective well-being and pain outcomes that need
      further confirmation in longitudinal research. However, the findings suggest that
      treatments which enhance subjective well-being (increasing positive affect and
      life satisfaction, and decreasing negative affect, e.g., via positive psychology
      exercises) and reducing pain catastrophizing (via e.g., cognitive-behavioral
      therapy) may have the highest potential for benefiting individuals with
      disability-associated chronic pain.

PMID- 29057665
TI  - Medications for substance use disorders (SUD): emerging approaches.
AB  - INTRODUCTION: Substance use disorders are a group of chronic relapsing disorders
      of the brain, which have massive public health and societal impact. In some
      disorders (e.g., heroin/prescription opioid addictions) approved medications have
      a major long-term benefit. For other substances (e.g., cocaine, amphetamines and
      cannabis) there are no approved medications, and for alcohol there are approved
      treatments, which are not in wide usage. Approved treatments for tobacco use
      disorders are available, and novel medications are also under study. Areas
      covered: Medication-based approaches which are in advanced preclinical stages, or
      which have reached proof-of concept clinical laboratory studies, as well as
      clinical trials. Expert opinion: Current challenges involve optimizing
      translation between preclinical and clinical development, and between clinical
      laboratory studies to therapeutic clinical trials. Comorbidities including
      depression or anxiety are challenges for study design and analysis. Improved
      pharmacogenomics, biomarker and phenotyping approaches are areas of interest.
      Pharmacological mechanisms currently under investigation include modulation of
      glutamatergic, GABA, vasopressin and kappa-receptor function, as well as
      inhibition of monoamine re-uptake. Other factors that affect potential market
      size for emerging medications include stigma, availability of treatment settings,
      adoption by clinicians, and the prevalence of persons with SUD who are not
      actively treatment-seeking.

PMID- 29057669
TI  - Patient-reported outcomes in moderate-to-severe allergic asthmatics treated with
      omalizumab: a systematic literature review of randomized controlled trials.
AB  - OBJECTIVE: Randomized controlled trials (RCTs) have established the safety and
      efficacy of omalizumab on clinical parameters, and have also evaluated its impact
      on patient-reported outcomes (PROs). The purpose of this systematic literature
      review was to review published data based on PRO endpoints in order to determine
      the benefit of omalizumab as add-on therapy to inhaled corticosteroids in
      patients with moderate-to-severe persistent allergic asthma. METHODS: A
      systematic literature review was conducted of reference databases and recent
      conferences. RCTs of add-on omalizumab therapy in adults, adolescents, and
      children with moderate-to-severe persistent asthma were included. Two researchers
      independently screened and reviewed articles with regards to inclusion and
      exclusion criteria for relevant studies. RESULTS: Twenty-six trials met the
      criteria for inclusion. Of these, PRO measures were included in 19 trials to
      capture the impact of omalizumab on symptoms, 11 assessed patients for health
      related quality-of-life (HRQoL), and four evaluated asthma control. Other PROs
      related to global evaluation of treatment effectiveness and work productivity.
      Overall, results demonstrated a significant difference across most PROs in favor
      of omalizumab add-on therapy vs placebo or comparators. CONCLUSIONS: PROs are an
      integral part of outcome assessment in clinical trials related to asthma. The
      RCTs reviewed demonstrate that omalizumab treatment improves PROs in patients
      with moderate-to-severe persistent allergic asthma, particularly symptom control
      and HRQoL.

PMID- 29057670
TI  - Do parents and children agree on rating a child's HRQOL? A systematic review and
      Meta-analysis of comparisons between children with attention deficit
      hyperactivity disorder and children with typical development using the PedsQLTM.
AB  - PURPOSE: This meta-analysis was conducted to assess differences in a child's
      health-related quality of life (HRQOL) as reported by the child and their parents
      using the Pediatric Quality of Life InventoryTM, and the effects in both children
      with attention deficit hyperactivity disorder (ADHD) and those with typical
      development. METHODS: Eight studies encompassing 16 independent groups met the
      inclusion criteria and were combined and compared in this meta-analysis. Fixed
      effect analysis was applied in the subgroup analysis to compare differences
      between children with ADHD and those with typical development. RESULTS: Small to
      moderate magnitudes of parent-child discrepancies were found in the ratings of
      the children's HRQOL both in those with ADHD (g = -0.23 [-0.33, -0.13], p <
      0.001, physical HRQOL; g = -0.60 [-0.71, -0.48], p < 0.001, psychosocial HRQOL)
      and in those with typical development (g = -0.27 [-0.31, -0.23], p < 0.001,
      physical HRQOL; g = -0.29 [-0.33, -0.25], p < 0.001, psychosocial HRQOL) except
      for emotional HRQOL in children with typical development (g = 0.003 [-0.04,
      0.04], p = 0.90). The parent-child discrepancy in rating the child's psychosocial
      HRQOL was significantly larger in the children with ADHD than in those with
      typical development. CONCLUSIONS AND IMPLICATIONS: This meta-analysis suggests
      that a child's HRQOL may be assessed in children and adolescents with ADHD both
      by parent proxy- and child self-reports. Parent-child discrepancies, especially
      in psychosocial HRQOL, and sources of discrepancy need to be addressed when
      assessing the child's HRQOL and planning interventions in children with ADHD.
      Implications for Rehabilitation Parents reported a significantly worse health
      related quality of life of their children than both the children with attention
      deficit hyperactivity disorder and those with typical development. A child's
      health-related quality of life needs to be assessed both by parent proxy and self
      reports of the children. Children with attention deficit hyperactivity disorder
      and those with typical development differed significantly in parent-child
      discrepancy in child's psychosocial health-related quality of life, but not in
      physical health-related quality of life. Parent-child discrepancies, especially
      in psychosocial health-related quality of life, and sources of discrepancy (e.g.,
      child, parent or family characteristics) need to be addressed when assessing the
      child's health-related quality of life and planning interventions in children
      with attention deficit hyperactivity disorder.

PMID- 29057671
TI  - Retinal vascular resistance in arterial hypertension.
AB  - PURPOSE: Retinal microcirculation represents an easily accessible, non-invasive,
      in-vivo possibility to assess early microvascular changes. In addition to the
      assessment of functional (e.g. retinal capillary flow, RCF) and retinal
      arteriolar structural parameters (e.g. wall-to-lumen-ratio, WLR) we now suggest a
      new parameter reflecting the resistance in small retinal arterioles (RVR).
      MATERIAL AND METHODS: In 45 normotensive (NT) subjects and 123 patients with
      hypertension stage 1 (HT) we assessed RCF, WLR, arteriolar diameter, lumen
      diameter and wall cross section area in the retinal circulation by using scanning
      laser Doppler flowmetry (SLDF). Mean arterial pressure (MAP) was measured
      immediately before the SLDF measurement and retinal vascular resistance was
      calculated (RVR = MAP/RCF). In a separate study the test-retest reliability was
      determined in 6 volunteers from our clinical staff by assessing RVR three times
      within six weeks. RESULTS: The analysis of the volunteers revealed a coefficient
      of variation for RVR of 7.75 +/- 2.11% and Cronbach's alpha was 0.90. WLR, a
      marker of vascular remodeling did not differ between NT and HT. In contrast, RCF
      and inner diameter of the retinal arterioles (ID) were significantly lower (RCF:
      p = .045 and ID: p = .001) in the HT group than in the NT group and RVR was
      significantly higher in the HT group than in the NT group (p < .001). In both
      groups we found no correlation of RVR with age, but a significant correlation of
      RVR with WLR (NT: r = 0.34, p = .006; HT: r = 0.25, p = .01), indicating that the
      RVR reflects vascular remodeling in the retinal circulation. CONCLUSION: Our data
      showed an increased retinal vascular resistance in hypertensive patients compared
      to non-hypertensive patients prior to the occurrence of structural retinal
      vascular remodeling. The correlation between RVR and WLR indicates that RVR is a
      reliable, non-invasive and early-sensitive marker of vascular remodeling in early
      hypertension.

PMID- 29057672
TI  - Chemical meningitis related to intra-CSF liposomal cytarabine.
AB  - Therapeutic options of leptomeningeal metastases include intra-cerebrospinal
      fluid (CSF) chemotherapy. Among intra-CSF agents, liposomal cytarabine has
      advantages but can induce specific toxicities. A BRAF-V600E-mutated melanoma
      leptomeningeal metastases patient, treated by dabrafenib and liposomal
      cytarabine, presented after the first injection of liposomal cytarabine with
      hyperthermia and headaches. Despite sterile CSF/blood analyses, extended
      intravenous antibiotics were given and the second injection was delayed. The
      diagnosis of chemical meningitis was finally made. Dose reduction and appropriate
      symptomatic treatment permitted the administration of 15 injections of liposomal
      cytarabine combined with dabrafenib. A confirmation of the diagnosis of chemical
      meningitis is essential in order (1) not to delay intra-CSF or systemic
      chemotherapy or (2) to limit the administration of unnecessary but potentially
      toxic antibiotics.

PMID- 29057673
TI  - Maternal distress in the context of their child's type 1 diabetes: exploring the
      role of adaptive maternal emotion regulation on child outcomes.
AB  - Parents of children with Type 1 diabetes (T1D) experience high levels of
      distress, which may negatively impact child functioning. However, little is known
      about mechanisms that may buffer the adverse impact of parental distress. The
      current study explored the possible buffering role of maternal adaptive cognitive
      emotion regulation (CER) for the relationship between maternal distress and child
      psychological functioning. Forty-three children with T1D (8-15 years) completed
      measures assessing trait anxiety and depressive symptoms. Their mothers reported
      on general distress, illness-related parenting stress, and adaptive CER. Maternal
      illness-related parenting stress (but not general distress) was significantly
      associated with child psychological functioning. No buffering role for maternal
      adaptive CER was observed. As the current study is rather preliminary, future
      research using other methods to examine maternal adaptive CER, and examining
      other parental variables that may buffer against the negative impact of parental
      distress is warranted.

PMID- 29057674
TI  - All-cause hospitalization and associated costs in patients with schizophrenia or
      bipolar disorder initiating long-acting injectable antipsychotics.
AB  - OBJECTIVE: To compare all-cause hospitalization and associated costs among
      patients with schizophrenia or bipolar disorder (BD) treated with long-acting
      injectable antipsychotics (LAIs). METHODS: The Truven MarketScan Medicaid claims
      database was used to identify patients with schizophrenia; MarketScan Medicaid
      and commercial claims databases were used to identify BD. Adult patients with >=1
      LAI claim from January 1, 2013-June 30, 2014 (ID period) were identified. The
      first day of LAI initiation was the index date; patients were followed for >=1
      year. Logistic and general linear regression models were used to estimate the
      risk of hospitalization and associated costs. RESULTS: Adjusted analyses showed
      that, in the schizophrenia cohort, risks of hospitalization were statistically
      significantly higher in the haloperidol [OR (95% CI) = 1.51 (1.05-2.16); HR (95%
      CI) = 1.35 (1.05-1.73)] and risperidone [OR (95% CI) = 1.58 (1.07-2.33); HR (95%
      CI) = 1.33 (1.01-1.74)] cohorts than in the aripiprazole once monthly extended
      release (AOM 400) cohort. Similarly, in patients with BD, risks of
      hospitalization were significantly higher in haloperidol [OR (95% CI) = 1.49
      (1.01-2.19); HR (95% CI) = 1.33 (1.03-1.73)] and risperidone [OR (95% CI) = 1.78
      (1.19-2.66); HR (95% CI) = 1.33 (1.01-1.75)] than in AOM400. No statistically
      significant differences in hospitalization costs were observed in either disease
      group. CONCLUSIONS: Although the study results may be subject to confounding
      variables that are not contained in claims databases, such as disease severity,
      it appears that AOM400 may be more effective than haloperidol and risperidone
      LAIs among patients with schizophrenia or BD.

PMID- 29057675
TI  - Hydro-alcoholic media effects on theophylline release from sesamum polysaccharide
      gum matrices.
AB  - Concomitant ingestion of alcohol and medications can greatly affect drug plasma
      concentrations as dose dumping or failure may occur as a result of the fact that
      formulation excipients may not always be resistant to alcohol. In this study, a
      natural polysaccharide (Sesamum radiatum gum) (SG) was extracted, characterized
      and used to formulate sustained release theophylline compacts to study the effect
      of varying alcohol concentrations (v/v) in dissolution media on drug release from
      these compacts. X-ray powder diffraction showed that the extracted gum was
      amorphous in nature with the powder having excellent compaction properties as
      observed with its compact being significantly harder than those prepared with
      pure hydroxypropyl methyl cellulose (HPMC) K4M. X-ray microtomography showed that
      the compacts produced were homogenous in nature, however, swelling studies showed
      failure of the compacts at the highest concentration of absolute ethanol used
      (40% v/v). Dissolution studies showed similarity at all levels of alcohol tested
      (f2 = 57-91) in simulated gastric (0.1 N HCl, pH 1.2) and intestinal fluids
      (phosphate buffer, pH 6.8) for the HPMC compacts whereas dissimilarity only
      occurred for the SG compacts at the highest alcohol concentration in both media
      (f2 = 35). The suitability of SG as a matrix former that can resist alcoholic
      effects therefore makes it suitable as an alternative polymer with wider
      applications for drug delivery.

PMID- 29057676
TI  - Comparison of the effects of mobile technology AAC apps on programming visual
      scene displays.
AB  - Parents and professionals who work with individuals who use augmentative and
      alternative communication (AAC) face tremendous time pressures, especially when
      programming vocabulary in AAC technologies. System design (from programming
      functions to layout options) necessitates a range of skills related to
      operational competence and can impose intensive training demands for
      communication partners. In fact, some AAC applications impose considerable
      learning demands, which can lead to increased time to complete the same
      programming tasks. A within-subject design was used to investigate the
      comparative effects of three visual scene display AAC apps (GoTalk Now,
      AutisMate, EasyVSD) on the programming times for three off-line programming
      activities, by adults who were novices to programming AAC apps. The results
      indicated all participants were able to create scenes and add hotspots during off
      line programming tasks with minimal self-guided training. The AAC app that had
      the least number of programming steps, EasyVSD, resulted in the fastest
      completion times across the three programming tasks. These results suggest that
      by simplifying the operational requirements of AAC apps the programming time is
      reduced, which may allow partners to better support individuals who use AAC.

PMID- 29057677
TI  - Effect of different polysorbates on development of self-microemulsifying drug
      delivery systems using medium chain lipids.
AB  - The primary objective of this study was to develop lipid-based self
      microemulsifying drug delivery systems (SMEDDS) without using any organic
      cosolvents that would spontaneously form microemulsions upon dilution with water.
      Cosolvents were avoided to prevent possible precipitation of drug upon dilution
      and other stability issues. Different polysorbates, namely, Tween 20, Tween 40,
      Tween 60, and Tween 80, were used as surfactants, and Captex 355 EP/NF (glycerol
      tricaprylate/caprate) or its 1:1 mixture with Capmul MCM NF (glycerol
      monocaprylocaprate) were used as lipids. Captex 355-Tween-water ternary phase
      diagrams showed that oil-in-water microemulsions were formed only when the
      surfactant content was high (80-90%) and the lipid content low (10-20%). Thus,
      mixtures of Tweens with Captex 355 alone were not suitable to prepare SMEDDS with
      substantial lipid contents. However, when Captex 355 was replaced with the 1:1
      mixture of Captex 355 and Capmul MCM, clear isotropic microemulsion regions in
      phase diagrams with sizes in the increasing order of Tween 20 < Tween 40 < Tween
      60 < Tween 80 were obtained. Tween 80 had the most profound effect among all
      surfactants as microemulsions were formed with lipid to surfactant ratios as high
      as 7:3, which may be attributed to the presence of double bond in its side chain
      that increased the curvature of surfactant layer. Thus, lipid-surfactant mixtures
      containing 1:1 mixture of medium chain triglyceride (Captex 355) and
      monoglyceride (Capmul MCM) and as low as 30% Tween 80 were identified as organic
      cosolvent-free systems for the preparation of SMEDDS. Formulations with a model
      drug, probucol, dispersed spontaneously and rapidly upon dilution with water to
      form microemulsions without any drug precipitation.

PMID- 29057678
TI  - Healthfulness and nutritional composition of Canadian prepackaged foods with and
      without sugar claims.
AB  - The objective of this study was to evaluate differences in calories, nutrient
      content, overall healthfulness, and use of sweetener ingredients between products
      with and without sugar claims. Consumers assume products with sugar claims are
      healthier and lower in calories. It is therefore important claims be found on
      comparatively healthier items. This study is a cross-sectional analysis of the
      University of Toronto's 2013 Food Label Database. Subcategories where at least 5%
      of products (and n >= 5) carried a sugar claim were included (n = 3048).
      Differences in median calorie content, nutrient content, and overall
      healthfulness, using the Food Standards Australia/New Zealand Nutrient Profiling
      Scoring criterion, between products with and without sugar claims, were
      determined. Proportion of products with and without claims that had excess free
      sugar levels (>=10% of calories from free sugar) and that contained sweeteners
      was also determined. Almost half (48%) of products with sugar claims contained
      excess free sugar, and a greater proportion contained sweeteners than products
      without such claims (30% vs 5%, chi2 = 338.6, p < 0.0001). Overall, products with
      sugar claims were "healthier" and had lower median calorie, free sugar, total
      sugar, and sodium contents than products without claims. At the subcategory
      level, reductions in free sugar contents were not always met with similar
      reductions in calorie contents. This study highlights concerns with regards to
      the nutritional composition of products bearing sugar claims. Findings can
      support educational messaging to assist consumer interpretation of sugar claims
      and can inform changes in nutrition policies, for example, permitting sugar
      claims only on products with calorie reductions and without excess free sugar.

PMID- 29057679
TI  - Optimisation of chloroquine phosphate loaded nanostructured lipid carriers using
      Box-Behnken design and its antimalarial efficacy.
AB  - Chloroquine was once the most widely used antimalarial for nearly eight decades
      for its safety, efficiency, stability, low cost and finally for its less toxic
      nature. But its use and efficacy got slowly decreased with the increase of
      chloroquine resistant strains of Plasmodium species throughout the world. Lipid
      based nanodrug delivery systems have been very popular in the recent times as
      they are very less toxic, have drug targeting capabilities and also reduces the
      dosing frequency by increasing efficacy of the drug. In the present research
      work, response surface methodology was employed to optimise chloroquine phosphate
      (CQ) loaded nanostructured lipid carriers (NLCs) using a modified double emulsion
      technique. The optimised CQ loaded NLC showed a particle size of 66.50 +/- 1.21
      nm, PDI of 0.210 +/- 0.016, ZP of +38.4 +/- 1.44 and EE of 78.2 +/- 1.2%,
      respectively. The in vitro and in vivo antimalarial studies of CQ loaded NLCs
      showed an enhanced antimalarial efficacy of the nanoformulation with a better
      suppression of parasitemia and with an increased efficacy of more than 23% in
      comparison to pure drug. This study demonstrated that by loading a drug into an
      NLCs system can help in overcoming the problems associated with the present
      antimalarials available.

PMID- 29057680
TI  - The association of renin-angiotensinogen system genes polymorphisms and
      idiopathic recurrent pregnancy loss.
AB  - The most common complication of pregnancy is idiopathic recurrent pregnancy loss
      (RPL). To identify the contribution of gene polymorphisms to this condition, we
      evaluated the association between RPL and the angiotensinogen (AGT), angiotensin
      receptor 1 (AGTR1) and Angiotensinogen converting enzyme (ACE). In this case
      control study, the frequency of AGT (rs4762 and rs699), AGTR1 (rs5186) and ACE
      insertion/deletion (rs4340) polymorphisms in 202 idiopathic RPL women was
      compared with 210 women with no history of abortion, using tetra-primer ARMS-PCR.
      Polymorphisms were analysed by logistic regression analysis according to
      inheritance models. The CT genotype of AGT rs4762, the CC genotype of AGT rs699
      and the AC genotype of AGTR1 rs5186 in a co-dominant inheritance model were
      associated with idiopathic RPL (OR = 1.63, 95% CI = 1.07-2.49 of CT versus CC; OR
      = 5.97, 95% CI = 1.28-27.82 of CC versus TT; and OR = 1.99, 95% CI = 1.22-3.07 of
      AC versus AA). The allele frequency of AGT rs699 and AGTR1 rs5186 polymorphisms,
      but not AGT rs4762 and ACE rs4340 polymorphisms were significantly different
      between women with RPL patients and controls (p = 0.020, p = 0.003, p = 0.105 and
      p = 0.065, respectively). These results show that there is a significant
      relationship between AGT (rs699) and AGTR1 (rs5186) polymorphisms and idiopathic
      RPL in the Iranian population.

PMID- 29057681
TI  - Liquid biopsy in non-small cell lung cancer: a key role in the future of
      personalized medicine?
AB  - INTRODUCTION: Liquid biopsies, especially the analysis of circulating tumor DNA
      (ctDNA), as a novel and non-invasive method for the diagnosis and monitoring of
      non-small cell lung cancer (NSCLC) have already been implemented in clinical
      settings. The majority of ctDNA is released from apoptotic or necrotic tumor
      cells, thus reflecting the genetic profile of a tumor. Numerous studies have
      reported a high concordance in mutation profiles derived from liquid biopsy and
      tissue biopsy, especially in driver genes. Liquid biopsy could overcome the
      clonal heterogeneity of tumour biopsy, as it provides a single snapshot of a
      tumour tissue. Moreover, non-invasiveness is the biggest advantage for liquid
      biopsy, and the procedure can be repeatedly performed during the treatment for
      the purpose of monitoring. Therefore, ctDNA could act as a potential
      complementary method for tissue biopsies in diagnosis, prognostic, treatment
      response and resistance. Areas covered: This review summarizes the recent
      advancements in liquid biopsy with a focus on NSCLC, including its applications
      and technologies associated with assessing ctDNA. The authors conclude the review
      by discussing the challenges associated with liquid biopsy. Expert commentary:
      The analysis of ctDNA represents a promising method for liquid biopsy, which will
      be a novel and potentially complementary method in diagnosis, treatment and
      prognostic in NSCLC at all stages.

PMID- 29057682
TI  - Improving diagnosis of childhood arterial ischaemic stroke.
AB  - INTRODUCTION: At least half of childhood stroke survivors suffer long-term
      impairments. Rapid identification of stroke is essential to minimize the extent
      of injury by restoring perfusion to viable brain. Improving diagnosis of
      childhood stroke requires correct identification of stroke by prehospital and
      emergency physicians, rapid performance of appropriate neuroimaging to confirm
      infarction, and targeted investigations to determine underlying causes, which
      guide treatment decisions to reduce recurrence risk. Areas covered: This review
      will summarize the barriers to rapid stroke diagnosis in pre-hospital and
      emergency department settings, describe recent progress in understanding of the
      spectrum, presenting clinical features and differential diagnosis of childhood
      stroke, discuss clinical stroke recognition tools which improve diagnostic
      accuracy, and their application to children. Recent advances in the diagnostic
      evaluation of stroke will be presented, and the review will conclude by outlining
      priorities for future research. Expert commentary: Development of coordinated
      systems of acute care are essential to facilitate rapid diagnosis of childhood
      stroke. Recent advances in acute pediatric stroke care include consensus
      recommendations for primary pediatric stroke centers and implementation of
      standardized Pediatric Code Stoke protocols, which result in shorter time to
      diagnosis, selection of MRI as the initial imaging modality, and increased access
      to reperfusion therapies.

PMID- 29057683
TI  - Second trimester growth velocities: assessment of fetal growth potential in SGA
      singletons.
AB  - OBJECTIVE: To evaluate the validity of second trimester growth velocities as
      measures of fetal growth potential in Small-for-Gestational-Age (SGA) singletons.
      METHODS: Second trimester growth velocities for biparietal diameter (BPD), head
      circumference (HC), abdominal circumference (AC) and femur diaphysis length (FDL)
      were determined by linear regression analysis or direct measurement in 53 SGA
      singletons with normal growth outcomes (SGA N Group) and 73 with growth
      restriction (SGA GR) based on a composite fetal growth pathology score (FGPS1).
      The latter were subdivided into six groups based on their growth restriction
      pattern (Patterns group). Similar data were available for 118 singletons with
      normal neonatal growth outcomes (NNGO group). Coefficients of determination (R2)
      and growth velocities for each anatomical parameter were compared between
      Patterns subgroups and the SGA N, SGA GR and NNGO groups. RESULTS: Median R2
      values in the six Patterns subgroups ranged from 98.2% (Pattern 2, FDL) to 99.9%
      (Pattern 5, AC). Within each anatomical parameter set, no significant differences
      were found (Kruskal-Wallis). Patterns subgroup data were pooled to form the SGA
      GR group for each anatomical parameter. Mean values for the three main groups
      ranged from 98.4% (SGA N, FDL) to 99.6% (SGA N, HC). No significant differences
      between groups (ANOVA) were found for any anatomical parameter (ANOVA). Only 1.7
      3.8% had R2 values <95th%. No significant differences in median second trimester
      growth velocities among different Patterns subgroups were found for any
      anatomical parameter. In the SGA N and SGA GR groups, mean BPD and HC values did
      not differ but were significantly smaller than the NNGO group values. No
      differences in mean FDL values were seen. With AC, all three means were
      significantly different, having the following order: NNGO > SGA N > SGA GR. Of
      all 504 second trimester growth rates, 92.5% were within their respective 95%
      reference ranges. CONCLUSION: Growth in the second trimester is linear in fetuses
      at risk for growth restriction. Except for FDL, growth velocities were lower than
      those for fetuses with NNGO. Only AC had mean velocities that differed between
      the SGA N and the SGA GR groups. Since most velocities (92.5%) were within normal
      reference ranges, they are reasonable measures of growth potential in fetuses at
      risk for growth restriction.

PMID- 29057685
TI  - Correction to: Ferriols Perez et al., Inadequate visits to the emergency
      department by pregnant women.

PMID- 29057684
TI  - Epidemiology of mental health comorbidity in psoriasis.
AB  - AIM: The occurrence of mental health comorbidities such as depression, anxiety,
      and suicidal ideation or behavior is not uncommon in the context of psoriasis.
      The negative influence of psoriatic disease on a patient's physical and mental
      well-being, in combination with overlapping pathophysiology, increase the risk
      for clinically significant psychiatric conditions. These psychiatric conditions,
      in turn, influence the patient's outlook and potentially, prognosis. Although the
      healthcare community increasingly recognizes the association of mental health
      comorbidities with psoriasis, the extent of the correlation is not fully
      appreciated. To better understand the relationship between mental health
      comorbidities and psoriasis, including prevalence, risk factors, and response of
      psychiatric comorbidities to psoriasis treatment, a narrative review of the
      published literature was conducted. METHODS: Data from epidemiologic,
      observational, and clinical studies demonstrate a substantially greater mental
      health comorbidity burden in patients with psoriasis compared with those without
      psoriasis or patients with other dermatologic conditions. RESULT: The influence
      of contemporary drug therapies on measures of depression and anxiety are
      predominantly positive, although further data are needed to better understand the
      effects of long-term therapy. CONCLUSION: Clinicians should consider the
      heightened potential for mental health comorbidities when determining an optimal
      management strategy for their patients with psoriasis.

PMID- 29057686
TI  - Treatment of asymptomatic uterine rupture of caesarean scar pregnancy in patient
      with advanced gestational age: case report.

PMID- 29057687
TI  - Safety and efficacy of intravenous iron administration for uterine bleeding or
      postpartum anaemia: a narrative review.
AB  - The management of iron deficiency anaemia (IDA) consists of oral or intravenous
      administration of iron supplements. The aim of this narrative review is to
      summarise information regarding the treatment of IDA in women who have postpartum
      anaemia or uterine bleeding with intravenous (IV) or oral iron supplements.
      Fourteen randomised control studies comparing IV to oral iron treatment for IDA
      in 2913 women with uterine bleeding or postpartum haemorrhage are included. All
      reviewed studies suggest that IV iron administration is important in treating the
      IDA in such women and in improving their physical performance and quality of
      life. Comparisons among intravenous iron supplements show advantages of ferric
      carboxymaltose over others in time of reaching desired haemoglobin and ferritin
      values and in adverse reactions. Despite the limitation that the above evidence
      emerges from not systematically collected data, our review highlights that new
      forms of IV iron supplements seem safe and efficient in treating IDA.

PMID- 29057689
TI  - Biotin for the treatment of nail disease: what is the evidence?
AB  - AIM: To describe the pharmacology, mechanism of action, and clinical reports
      using biotin to treat nail conditions. METHODS: A review of articles indexed for
      MEDLINE on PubMed using keywords 'biotin' and 'nail' was performed and applicable
      articles were selected for review. RESULTS: Clinical trials have shown an
      improvement in firmness, hardness, and thickness of brittle nails with oral
      biotin. There are some case reports and series demonstrating that oral biotin may
      improve triangular worn down nails, trachyonychia, and habit tic nail deformity.
      CONCLUSIONS: Oral biotin has been used to treat several nail conditions with
      promising results. Further larger clinical trials with controls are necessary to
      determine efficacy and optimal dosing.

PMID- 29057690
TI  - Detrimental effects of endometriosis on oocyte morphology in intracytoplasmic
      sperm injection cycles: a retrospective cohort study.
AB  - While an association can be addressed among endometriosis and subfertility, the
      causal relationship has not been elucidated yet. Impaired oocyte quality in
      endometriosis patients has been accused for the unsuccessful outcomes of assisted
      reproductive techniques. There are limited studies in literature evaluated
      association between endometriosis and oocyte morphology. We conducted this
      retrospective study to evaluate whether morphological abnormalities of oocytes
      are more common in women with endometriosis than women with diagnosis of male
      factor infertility as a source of healthy oocytes. Totally 1568 oocytes, 775
      (49.4%) in endometriosis groups and 793 (50.6%) in control group were evaluated
      for morphological parameters before ICSI cycles. Abnormal oocyte morphology was
      detected in 352 (22.4%) of 1568 oocytes. Of the abnormal oocytes, 208 (59.1%)
      were in endometriosis group and 144 (40.9%) in control group (p < .001). The
      following dysmorphisms were significantly higher in oocytes retrieved from
      endometriosis group: dark cytoplasm; dark, large or thin zona pellucida; and flat
      or fragmented polar body (p <  .05 for all). When morphological parameters for
      oocytes of endometriosis patients evaluated, the oocyte defects has increased
      significantly in endometriosis patients. These findings are thought to be useful
      to clarify the subfertility in endometriosis patient, which needs to be confirmed
      with further studies.

PMID- 29057691
TI  - The outcomes and risk factors of fetal bradycardia associated with external
      cephalic version.
AB  - OBJECTIVE: The objective of this study is to assess the outcomes and risk factors
      of fetal bradycardia after external cephalic version (ECV). METHODS: We performed
      a retrospective study of women who underwent ECV after 35 weeks of gestation in
      2010-2016. We assessed the birth outcomes, including umbilical cord artery pH,
      according to the duration of fetal bradycardia and the risk factors for
      bradycardia. RESULTS: Among 390 cases, 189 (48.5%) cases showed fetal bradycardia
      during or immediately after ECV. The duration of fetal bradycardia was <1 min (n
      = 82, 43.4%), <5 min (n = 168, 88.9%); and <10 min (n = 186, 98.4%). All cases
      showed a good prognosis. Fetal bradycardia lasting >10 min occurred in three
      cases; emergency cesarean section was performed in each case, with delivery after
      12-4 min of bradycardia. Two of three cases showed low Apgar scores at 5 min,
      with an umbilical cord arterial pH of <7.1. Lower maternal BMI and a prolonged
      ECV procedure were significantly associated with bradycardia (p for trend: .016
      and .015, respectively). CONCLUSIONS: Fetal bradycardia lasting >10 min after ECV
      was a risk factor for asphyxia. Thus, delivery should be completed within 10 min
      after bradycardia. A low maternal BMI and a prolonged ECV procedure were risk
      factors for bradycardia after ECV.

PMID- 29057688
TI  - ROCK as a therapeutic target for ischemic stroke.
AB  - INTRODUCTION: Stroke is a major cause of disability and the fifth leading cause
      of death. Currently, the only approved acute medical treatment of ischemic stroke
      is tissue plasminogen activator (tPA), but its effectiveness is greatly
      predicated upon early administration of the drug. There is, therefore, an urgent
      need to find new therapeutic options for acute stroke. Areas covered: In this
      review, we summarize the role of Rho-associated coiled-coil containing kinase
      (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK
      is a major regulator of cell contractility, motility, and proliferation. Many of
      these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells,
      pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in
      stroke pathophysiology, and the inhibition of such processes could improve stroke
      outcome. Expert commentary: ROCK is a potential therapeutic target for
      cardiovascular disease and ROCK inhibitors have already been approved for human
      use in Japan and China for the treatment of acute stroke. Further studies are
      needed to determine the role of ROCK isoforms in the pathophysiology of cerebral
      ischemia and whether there are further therapeutic benefits with selective ROCK
      inhibitors.

PMID- 29057692
TI  - Short birth-to-pregnancy intervals among African-born black women in Washington
      State.
AB  - BACKGROUND: Short birth-to-pregnancy intervals have been associated with adverse
      perinatal outcomes. Racial disparities in short birth-to-pregnancy intervals and
      adverse perinatal outcomes are also well known. However, little is known about
      birth-to-pregnancy intervals among African-born black women in the US and risk
      factors that contribute to short birth-to-pregnancy intervals in this population.
      OBJECTIVES: To investigate the risk and associated risk factors of short birth-to
      pregnancy intervals among African-born black women in Washington State. STUDY
      DESIGN: A retrospective cohort study using data from linked birth certificate and
      hospital discharge records for 18,984 consecutive, singleton birth pairs (1992
      2013) to African-born black (n = 3312), US-born white (n = 7839), and US-born
      black women (n = 7833) in Washington State. Logistic regression models were used
      to determine adjusted odds ratios (aOR) and 95% confidence intervals (CI).
      RESULTS: Women with short birth-to-pregnancy intervals (<6 months) comprised
      10.0% of African-born women, 4.3% of US-born white women, and 6.8% of US-born
      black women. African-born black women had 3-fold (aOR 3.44; 95%CI: 2.53-4.68) and
      1.5-fold (aOR 1.49; 95%CI: 1.28-1.74) higher risk of short birth-to-pregnancy
      intervals compared with US-born white women and US-born black women,
      respectively. Among African-born black women, those born in East Africa (aOR
      3.17; 95%CI: 1.92, 5.24) had higher odds of short birth-to-pregnancy intervals
      compared with those born in other regions of Africa. Maternal age >=35 years old
      (aOR 0.59; 95%CI: 0.35, 0.98), multiparity (aOR 0.73; 95%CI: 0.54-0.98), > 12
      years education (aOR 0.52; 95%CI: 0.38-0.71), and cesarean delivery in prior
      births (aOR 0.61; 95%CI: 0.44-0.84) were associated with lower odds of short
      birth-to-pregnancy intervals among African-born black women. CONCLUSIONS: African
      born black women have higher risk for short birth-to-pregnancy intervals compared
      with US-born white and black women. Several risk factors (age, parity, education,
      and prior delivery type) contribute to short birth-to-pregnancy intervals among
      African-born black women. Future studies may inform our understanding of factors
      affecting pregnancy spacing and family planning strategies among African-born
      black women.

PMID- 29057693
TI  - Combined modalities for the prevention of ovarian hyperstimulation syndrome
      following an excessive response to stimulation.
AB  - Although the classification and management of ovarian hyperstimulation syndrome
      (OHSS) are well described in the literature, little attention has been given to
      modalities that aim to prevent its occurrence. In this retrospective study, we
      sought to investigate whether a combination of modalities in addition to GnRH
      agonist triggering in GnRH antagonist cycles could result in better prevention of
      OHSS. The study included 170 hyperresponder patients who were stimulated with
      GnRH antagonist protocol and were triggered with GnRH agonist for final oocyte
      maturation. Freeze all embryos was performed in all patients. The intervention
      group included treatment with dopamine agonist and restarting the GnRH
      antagonist. Of the 170 patients included, 63 were included in the intervention
      group. Compared to no intervention, women in the intervention group were more
      likely to have: menses within 7 days of the oocyte retrieval, smaller ovarian
      diameter, the absence of free pelvic fluid, less hemoconcentration and higher
      serum sodium levels. It can be concluded that combining other modalities in
      addition to triggering with GnRH agonist in GnRH antagonist cycles, results in
      targeting several pathways that lead to OHSS and result in rapid resolution of
      signs of ovarian hyperstimulation.

PMID- 29057694
TI  - Early unexpected diagnosis of fetal life-limiting malformation; antenatal
      palliative care and parental decision.
AB  - INTRODUCTION: Conjoined twins are an infrequent occurrence in obstetric practice.
      Live-conjoined twins on a late preterm triplet pregnancy is an even rarer event.
      OBJECTIVE: The objective of this study is to emphasize the critical importance of
      perinatal palliative care and non-directive parental counseling, informed
      decision making and respect for autonomy following full disclosure of findings,
      fetal life-limiting diagnosis, treatment alternatives, maternal-fetal potential
      complications, and most likely perinatal outcomes. METHODS: Early surprise
      prenatal diagnosis, comprehensive parental counseling, palliative care, and
      perinatal care of a set of conjoined twins and a singleton. RESULTS: Cesarean
      delivery of a set of conjoined twins and a singleton at 34 weeks' gestation.
      Immediate neonatal death of the conjoined twins, intact survival, and discharge
      of the singleton. Review of the database on previously reported similar cases. It
      is very important to utilize simple and direct language for parents to understand
      the grave prognosis to the pregnancy. Care alternatives in view of the maternal
      physical risks and psychological impact of carrying a high order abnormal
      multiple pregnancy, along with the possible side effects on the singleton.

PMID- 29057695
TI  - A note on contemporary psychometrics.
AB  - Psychometrics provide the mathematical underpinnings for psychological
      assessment. From the late 19th century, a plethora of methodological research
      achievements equipped researchers and clinicians with efficient tools whose
      practical value becomes more evident in the era of the internet and big data.
      Nowadays, powerful probabilistic models exist for most types of data and research
      questions. As the usability of the psychometric scales is better comprehended,
      there is an increased interest in applied research outcomes. Paradoxically, while
      the interest in applications for psychometric scales increases, publishing
      research on the development and/or evaluation of those scales per se, is not
      welcomed by many relevant journals. This special issue in psychometrics is
      therefore a great opportunity to briefly review the main ideas and methods used
      in psychometrics, and to discuss the challenges in contemporary applied
      psychometrics.

PMID- 29057696
TI  - Effects of spontaneous recurrent seizures on cognitive function via modulation of
      SNAREs expression.
AB  - PURPOSE: To explore whether soluble N-ethylmaleimide-sensitive factor attachment
      protein receptors (SNARE) complexes are involved in cognitive dysfunction induced
      by spontaneous recurrent seizures (SRS). MATERIALS AND METHODS: An animal model
      of epilepsy was established by intraperitoneal injection of kainic acid (KA).
      Following the onset of SRS, the rats were divided into control group, KA-SRS
      group, KA+SRS group and KA+SRS+VAP group. Morris water maze and open field test
      were conducted to evaluate the cognitive function. Protein and mRNA levels of
      SNAREs complex were measured by Western-blot and RT-PCR, respectively. Besides,
      the Ca2+ concentration in the hippocampus was also detected. RESULTS: A delayed
      escape latency and a reduced number of platform crossings were found in the
      KA+SRS group. Meanwhile, a longer moving distance and time spent in central area
      were also observed during the open field test. Besides, the Ca2+ concentration in
      the hippocampus of the KA+SRS group was markedly increased. However, when
      compared with the KA+SRS group, all indices in the KA+SRS+VAP group were markedly
      improved. Moreover, the SNARE complexes in the hippocampus of the KA+SRS group
      were significantly increased when compared with both control group and KA+SRS+VAP
      group. CONCLUSIONS: Results of our study demonstrated that the cognitive
      dysfunction caused by SRS may be attributed to the modulation expression of SNARE
      complexes.

PMID- 29057697
TI  - Reply to: The effect of hyoscine butylbromide on the duration and progress of
      labor in primigravidae: a randomized controlled trial: methodological issues.

PMID- 29057698
TI  - Clinical uses of autofluorescence in ophthalmology.
AB  - Although it has been around for many years, historically autofluorescence has
      been difficult to capture. Developments in technology and camera sensors have
      made the process much easier and there is increasing research exploring
      autofluorescence patterns and how they can be used. This article explores the
      clinical uses of this technology in monitoring certain retinal conditions.

PMID- 29057699
TI  - Management of post-stroke mood and emotional disturbances.
AB  - INTRODUCTION: Mood and emotional disturbances are common in stroke patients. Out
      of diverse post-stroke emotional disturbances, depression, anxiety, emotional
      incontinence, anger proneness, and fatigue are frequent and important symptoms.
      These symptoms are distressing for both the patients and their caregivers, and
      negatively influence the patient's quality of life. The emotional symptoms are
      not apparent and are therefore often neglected by neurologists. Their
      phenomenology, predicting factors, and pathophysiology have been under-studied,
      and are under-recognized. In addition, well-designed clinical trials targeting on
      these symptoms are rare. Areas covered: This review will describe some of the
      most common or relevant post-stroke mood and emotional disturbances. The
      phenomenology, factors or predictors, and presumed etio-pathogenesis will be
      described. Current pharmacological and non-pharmacological management strategies
      of these diverse emotional disturbances will be discussed based on different
      pathophysiological mechanisms. Expert commentary: It is fortunate that these mood
      and emotional disturbances can be treated by various methods, including
      pharmacological and non-pharmacological therapy. To administer the appropriate
      therapy, we must understand the similarities and differences in the
      pathophysiological mechanisms associated with these emotional symptoms.

PMID- 29057700
TI  - Polymorphic lymphoproliferative disorders in patients with rheumatoid arthritis
      are associated with a better clinical outcome.
AB  - OBJECTIVES: The characteristics of lymphoproliferative disorders (LPD) in
      patients with rheumatoid arthritis (RA) remain unclear. Therefore, we
      retrospectively analyzed the clinical characteristics of these patients in our
      department. METHODS: Twenty RA patients who developed LPD between April 2003 and
      August 2016 in our department were analyzed. RESULTS: All of the RA patients who
      developed LPD had been treated with methotrexate (MTX). The median weekly and
      total dosages of MTX were 6.8 mg/week and 2530 mg, respectively. The median
      duration of MTX administration was eight years. Nineteen patients (95%) achieved
      complete remission (CR) and 15 (75%) achieved CR with MTX cessation alone. Based
      on the pathological findings, we divided MTX-associated LPD patients into two
      groups (n = 16); polymorphic LPD (31%) and other groups. CR with MTX cessation
      alone was achieved in 5 (100%) and 6 (54.5%) patients in the polymorphic LPD and
      other groups, respectively (p = .12). Moreover, the duration from the cessation
      of MTX to CR was significantly shorter in the polymorphic LPD group than in the
      other group (5.3 months vs 12.6 months, p = .01, respectively). CONCLUSION:
      Polymorphic LPD, which was the most frequent pathological diagnosis in this
      cohort, was associated with a higher incidence of CR and a significantly shorter
      duration to CR.

PMID- 29057702
TI  - Pharmacological treatment of patients with paraphilic disorders and risk of
      sexual offending: An international perspective.
AB  - OBJECTIVES: The present study aims to evaluate existing policy and practice
      relating to the use of pharmacological treatments with patients suffering from
      paraphilic disorders who are at risk of committing further sexual offences.
      METHODS: A systematic literature search was conducted to document current legal
      policies across 26 different countries. In addition, a questionnaire assessing
      the practice of pharmacological treatment was sent to practitioners involved in
      the treatment of patients with paraphilic disorders. RESULTS: Legal policies
      concerning the preconditions of using pharmacological treatments differ
      considerably between countries, and for most jurisdictions do not exist. Drawing
      on the responses of 178 practitioners, pharmacological agents are a useful
      addition to psychotherapeutic interventions, especially with those patients
      classified as medium or high risk for sexually violent behaviours. It would
      appear that most patients are medically examined, are informed of the risks and
      possible side effects before treatment commences and are also obliged to sign a
      consent form. CONCLUSIONS: Although pharmacological agents can be seen as an
      intrusion into a patients' sexual self determination, results indicate that
      ethical and clinical standards are being met in the majority of cases. However,
      further promotion of current WFSBP treatment guidelines would help to standardise
      practice across North American and European countries.

PMID- 29057701
TI  - The relationship between the sensory responses to ankle-joint loading and
      corticomotor excitability.
AB  - PURPOSE: Maintaining joint stability is dependent on the ability of the nervous
      system to sense and react to potentially injurious loads. In attempts to
      understand the neurophysiologic mechanisms underlying joint stability, this
      afferent and efferent activity has been quantified separately at the cortical,
      segmental and peripheral levels using various electrophysiologic techniques in
      vivo. However, no studies have attempted to quantify sensory and motor activation
      at multiple levels of the nervous system in a single subset, to understand
      potential adaptations for optimizing joint stability. MATERIALS AND METHODS:
      Muscle spindle afferent activity and sensory cortex event-related
      desynchronization were quantified during ankle-joint loading; and motor
      excitability was assessed through transcranial magnetic stimulation and the
      Hoffmann reflex in a subset of 42 able-bodied individuals. Microneurography and
      electroencephalography were used to collect the muscle spindle afferent and
      sensory cortex activation, respectively, as joint load was applied using an ankle
      arthrometer. Separately, motor-evoked potentials were obtained from the tibialis
      anterior (TA) and soleus (SOL) using transcranial magnetic stimulation over the
      motor cortex, and compared to the reflexive responses evoked via sciatic nerve
      electrical stimulation. RESULTS: Correlation coefficients revealed significant
      correlations between the motor threshold of the soleus and early muscle spindle
      afferent activity (r = -0.494) and early cortical event-related desynchronization
      (r = 0.470), as well as tibialis anterior motor-evoked potential size and late
      muscle spindle afferent activity (r = 0.499). CONCLUSIONS: The results of this
      study highlight the nervous system's capability to offset motor output based on
      the volume of sensory input at the segmental and cortical levels.

PMID- 29057703
TI  - The risk of second primary malignancy in patients with stage Ia non-small cell
      lung cancer: a U.S. population-based study.
AB  - BACKGROUND: Lung cancer is one of the most common cancers worldwide. Patients
      with early stage lung cancer have improved long-term survival. With the
      introduction of low-dose CT scan, more patients are going to be diagnosed at an
      early stage. However, there is limited data on the risk of second primary
      malignancies (SPMs) in these subsets of patients in the United States. METHODS:
      We utilized SEER-13 (Surveillance, Epidemiology and End Results) registry to
      obtain Multiple Primary- Standardized Incidence Ratio and an Absolute Excess Risk
      between January 2004 and December 2010 for patients with Stage Ia non-small cell
      lung cancer. RESULTS: The database comprised of 12,246 patients. A total of 1431
      (11.68%) patients developed 1563 SPMs with an observed to expected (O/E) ratio of
      2.07 (95% CI = 1.92-2.23, p < .001) in patients with adenocarcinoma and 2.05 (95%
      CI = 1.92-2.19, p <  .001) in squamous cell carcinoma group. CONCLUSIONS: This
      study showed an excess risk of SPMs in patients with early stage non-small cell
      lung cancer. We recommend a close follow-up, paying attention to concerning
      symptoms or examination findings and judicious use of age-appropriate cancer
      screening.

PMID- 29057704
TI  - The analgesic action of desmopressin in renal colic.

PMID- 29057705
TI  - Lexical processing and distributional knowledge in sound-spelling mapping in a
      consistent orthography: A longitudinal study of reading and spelling in dyslexic
      and typically developing children.
AB  - This study examined the ability to master lexical processing and use knowledge of
      the relative frequency of sound-spelling mappings in both reading and spelling.
      Twenty-four dyslexic and dysgraphic children and 86 typically developing readers
      were followed longitudinally in 3rd and 5th grades. Effects of word regularity,
      word frequency, and probability of sound-spelling mappings were examined in two
      experimental tasks: (a) spelling to dictation; and (b) orthographic judgment.
      Dyslexic children showed larger regularity and frequency effects than controls in
      both tasks. Sensitivity to distributional information of sound-spelling mappings
      was already detected by third grade, indicating early acquisition even in
      children with dyslexia. Although with notable differences, knowledge of the
      relative frequencies of sound-spelling mapping influenced both reading and
      spelling. Results are discussed in terms of their theoretical and empirical
      implications.

PMID- 29057706
TI  - Hydatid cyst involvement of both pulmonary arteries in a 14-year-old girl.
AB  - Hydatid disease is the most common mediterranean parasitic infection; it commonly
      affects the liver and lungs and rarely involves multiple organs. A 14-year-old
      girl presented with a 1-year history of dyspnoea and fatigue. She was found to
      have pulmonary hypertension owing to hydatid cysts in the right ventricle and
      both pulmonary arteries. After administration of albendazole she underwent
      pulmonary endarterectomy and a calcified hydatid cyst was removed from the right
      ventricle. She made a complete recovery and remained on albendazole for 6 months.

PMID- 29057707
TI  - Mixed matters: fluency impacts trust ratings when faces range on valence but not
      on motivational implications.
AB  - Facial features that resemble emotional expressions influence key social
      evaluations, including trust. Here, we present four experiments testing how the
      impact of such expressive features is qualified by their processing difficulty.
      We show that faces with mixed expressive features are relatively devalued, and
      faces with pure expressive features are relatively valued. This is especially
      true when participants first engage in a categorisation task that makes
      processing of mixed expressions difficult and pure expressions easy. Critically,
      we also demonstrate that the impact of categorisation fluency depends on the
      specific nature of the expressive features. When faces vary on valence (i.e. sad
      to happy), trust judgments increase with their positivity, but also depend on
      fluency. When faces vary on social motivation (i.e. angry to sad), trust
      judgments increase with their approachability, but remain impervious to
      disfluency. This suggests that people intelligently use fluency to make judgments
      on valence-relevant judgment dimensions - but not when faces can be judged using
      other relevant criteria, such as motivation. Overall, the findings highlight that
      key social impressions (like trust) are flexibly constructed from inputs related
      to stimulus features and processing experience.

PMID- 29057708
TI  - Characteristics of attention-related body sensations. Temporal stability and
      associations with measures of body focus, affect, sustained attention, and heart
      rate variability.
AB  - AIM: This study investigated the temporal stability and correlates of attention
      related body sensations that emerge without external stimulation during rest and
      due to focused attention on a body part. MATERIALS: To assess attention-related
      body sensations, participants were asked to focus on a freely chosen body area
      with closed eyes, and had to report whether the sensation of that area had
      changed. Self-report questionnaires were used to assess various aspects of body
      focus (body awareness, body responsiveness, somatosensory amplification,
      subjective somatic symptoms), and positive and negative affectivity. Previous
      experiences in body-mind therapies were also measured. PEBL Continuous
      Performance Test was used to assess sustained attention. Heart rate variability
      scores were based on a 3-minute long resting heart rate measurement. METHODS:
      Fifty-eight university students (22.3 +/- 3.95 years; 34 females) participated in
      the study. The stability of attention-related body sensations was measured 8
      weeks later on a randomly chosen sub-group (n = 28). RESULTS: Attention-related
      body sensations showed a mediocre temporal stability (rrho = 0.47, p = 0.012).
      People reporting attention-related body sensations showed significantly higher
      body awareness, somatosensory amplification, and resting heart rate; and
      marginally higher somatic symptoms. No relation was found with body-mind
      practice, body responsiveness, positive and negative affect, the vagal component
      of heart rate variability, and performance in the sustained attention task.
      CONCLUSION: Attention-related sensations are relatively stable over time. They
      are connected to some, but not to all of the aspects of body focus. Further
      studies are needed to elaborate the influencing stable and situational factors.

PMID- 29057709
TI  - Structural model of the full-length Ser/Thr protein kinase StkP from S.
      pneumoniae and its recognition of peptidoglycan fragments.
AB  - The unique eukaryotic-like Ser/Thr protein kinases of Streptococcus pneumoniae,
      StkP, plays a primary role in the cell division process. It is composed of an
      intracellular kinase domain, a transmembrane helix and four extracellular PASTA
      subunits. PASTA domains were shown to interact with cell wall fragments but the
      key questions related to the molecular mechanism governing ligand recognition
      remain unclear. To address this issue, the full-length structural model of StkP
      was generated by combining small-angle X-ray scattering data with the results of
      computer simulations. Docking and molecular dynamics studies on the generated
      three-dimensional model structure reveal the possibility of peptidoglycan
      fragment binding at the hinge regions between PASTA subunits with a preference
      for a bent hinge between PASTA3 and PASTA4.

PMID- 29057710
TI  - Integrative cancer pharmacogenomics to establish drug mechanism of action: drug
      repurposing.

PMID- 29057711
TI  - The effects of childhood maltreatment on brain structure in adults with eating
      disorders.
AB  - OBJECTIVES: Childhood maltreatment is a non-specific risk factor for eating
      disorders (EDs). However, so far, no study has assessed the impact of childhood
      maltreatment on brain structure of adults with EDs. Therefore, we investigated
      brain area volumes and fibre tract integrity of childhood maltreated (Mal) and
      non-maltreated (noMal) patients with EDs. METHODS: Thirty-six ED women and 16
      healthy women underwent an MRI scan, including acquisition of a diffusion tensor
      imaging (DTI) sequence and a high-resolution T1-weighted scan. ED participants
      were classified as Mal (18 patients) or noMal (18 patients) according to their
      childhood exposure to traumatic events assessed by the Childhood Trauma
      Questionnaire (CTQ). RESULTS: Significantly reduced grey matter volume was
      detected in the right paracentral lobule and in the left inferior temporal gyrus
      of Mal patients. DTI analyses revealed reduced white matter integrity in the
      corpus callosum, internal capsule, posterior thalamic radiation, longitudinal
      fasciculus and corona radiata of Mal patients. Negative correlations emerged
      between white/grey matter changes and CTQ emotional and physical neglect scores.
      CONCLUSIONS: These results show that childhood trauma affects the integrity of
      brain structures modulating brain processes, such as reward, taste and body image
      perception, which play a fundamental role in the psychopathology of EDs.

PMID- 29057712
TI  - Rapunzel syndrome (gastric trichobezoar), a rare presentation with generalised
      oedema: case report and review of the literature.
AB  - Rapunzel syndrome is a rare form of gastric trichobezoar. A 4-year-old girl
      presented with generalised oedema and an epigastric mass. Her family was of a
      relatively low socio-economic background. There was microcytic hypochromic
      anaemia, hypoalbuminaemia and an elevated alpha1-antitrypsin clearance. Abdominal
      ultrasound and non-contrast computed tomography demonstrated a heterogeneous mass
      related to the stomach. Upper gastro-intestinal tract endoscopy failed to remove
      it. Surgical laparotomy was undertaken through a single anterior gastrotomy
      incision and a large mass was extracted which was a cast of the duodenum and
      stomach and had a tail of approximately 60 cm in length which extended to the
      jejunum. Low socio-economic status, child neglect and pica are risk factors for
      trichobezoars. Surgical laparotomy is the optimal treatment of large bezoars.

PMID- 29057713
TI  - Estrogenic activity of zearalenone, alpha-zearalenol and beta-zearalenol assessed
      using the E-screen assay in MCF-7 cells.
AB  - Mycotoxins, including zearalenone (ZEA), can occur worldwide in cereals. They can
      enter the food chain and cause several health disorders. ZEA and its derivatives
      (alpha-zearalenol, alpha-ZOL and beta-zearalenol, beta-ZOL) have structural
      analogy to estrogen, thus they can bind to estrogen receptors (ERs). In order to
      characterize the estrogenic activity of ZEA, alpha-ZOL and beta-ZOL, the
      proliferation of ER-positive human breast cancer cells (MCF-7) exposed to these
      mycotoxins was measured. After exposure at levels ranging from 6.25 to 25 uM,
      cell proliferation was evaluated by using the E-Screen bioassay. In accordance
      with previous studies, our results show the estrogenic activity of ZEA, alpha-ZOL
      and beta-ZOL in MCF-7 cells. This effect is related to ZEA and its metabolites
      being flexible enough to bind to mammalian ERs. The relative proliferative effect
      (RPE) ranged from 10% to 91%. The alpha-ZOL induced the highest proliferative
      effect due to its higher affinity for the ERs compared to the other mycotoxins.

PMID- 29057714
TI  - Dose-dependent effect of radiation on resorbable blast material titanium
      implants: an experimental study in rabbits.
AB  - BACKGROUND: Radiotherapy is a commonly used treatment modality in head and neck
      cancer; however, it also negatively affects healthy structures. Direct damage to
      oral soft and hard tissue frequently occurs with radiotherapy. In this study, we
      aimed to evaluate the effect of radiotherapy on bone surrounding titanium dental
      implants via biomechanical and molecular methods. MATERIALS AND METHODS: Fifty
      four implants were inserted in the left tibiae of 18 adult male New Zealand
      rabbits (3 implants in each rabbit). After 4 weeks of the implant surgery, the
      left tibiae of 12 rabbits were subjected to a single dose of irradiation (15 Gy
      or 30 Gy). Four weeks after the irradiation, rabbits were sacrificed and removal
      torque test was done for the biomechanical evaluation. Bone morphogenetic protein
      2 (Bmp-2) and fibroblast growth factor-2 (Fgf-2) expression analyses were
      performed with Real-time PCR. Statistical analysis was done using SPSS. RESULTS:
      The control group showed significantly higher removal torque value than the 15
      and 30 Gy irradiation groups, and the 15 Gy irradiation group had higher removal
      torque value than the 30 Gy irradiation group (p < .001). The 15 Gy and 30 Gy
      irradiation groups had significantly lower Bmp-2 and Fgf-2 mRNA expressions than
      the control group (p < .001). In addition, the 30 Gy irradiation group had
      significantly lower Bmp-2 (p < .01) and Fgf-2 mRNA expressions (p < .001) than
      the 15 Gy group. CONCLUSION: Radiotherapy with 15 and 30 Gy doses can adversely
      affect osseointegration of implants by reducing the quality of bone and impairing
      the bone-to-implant contact. The mechanism of action seems to be related to
      alterations in Bmp-2 and Fgf-2 mRNA expressions.

PMID- 29057715
TI  - Structural and functional alterations of the heart in Parkinson's disease.
AB  - : Parkinson's disease (PD) patients have most frequently heart failure. The cause
      of this increased prevalence is not known. We designed a study to assess the
      cardiac function and cardiac structure in patients with PD compared to a control
      group. METHODS: Cross-sectional study with 50 PD patients and 50 healthy matched
      controls. We performed electro and echocardiograms to all patients and controls.
      The measurements were blind. In addition, we performed a neurological assessment.
      RESULTS: PD patients had higher left ventricular mass index (114.2 +/- 38.4 vs.
      94.1 +/- 26.4 g/m2; P = 0.003) and higher left atrial volume (30.1 +/- 7.9 vs.
      26.7 +/- 6.2 ml/m2; P = 0.01). PD was an independent risk factor for elevated
      left ventricular filling pressures (OR = 2.7, CI 95% 2.2-6.3; P = 0.004).
      Concentric remodeling and left ventricular hypertrophy were associated with more
      advanced Hoehn and Yahr stages. Moreover, patients with more dysautonomia
      symptoms showed more left ventricular hypertrophy. Finally, PD group had longer
      QT interval than control group regardless of the drugs. CONCLUSIONS: PD is
      significantly associated with increased concentric left ventricular hypertrophy
      and diastolic dysfunction. Advanced stages of PD are associated with a more
      severe cardiac affection. These findings can explain the increase of heart
      failure in PD patients. Cardiomyopathy could be a non-motor parkinsonian symptom.

PMID- 29057716
TI  - Safety assessment on microbial and heavy metal concentration in Clarias
      gariepinus (African catfish) cultured in treated wastewater pond in Kumasi,
      Ghana.
AB  - This study assesses the microbial and heavy metal distribution in African catfish
      (Clarias gariepinus) cultured in waste stabilization pond, and their subsequent
      suitability for human consumption. Treated wastewater-fed pond (WFP) was used in
      the culture of the fish with a non-wastewater fed pond (NWFP), fed with ground
      and rain water as control. Pond water, sediments and fish tissue (gill, liver,
      gut and skin) samples from both sources were analyzed for pathogens and heavy
      metal levels. Escherichia coli populations in the sediments and water from the
      WFP exceeded the maximum permissible limit by 2-3 log units as expected.
      Significantly higher levels of pathogen contamination were detected in the gut
      and skin of fish from the WFP than the NWFP. Heavy metal concentrations in all
      samples fell within the Food and Agricultural Organization (FAO)/World Health
      Organization (WHO) and National Oceanic and Atmospheric Administration (NOAA)
      permissible limits except for iron and cadmium. There were significantly higher
      heavy metal concentrations in gill and liver than the muscle. Even though iron
      recorded the highest concentrations in fish tissue, the concentrations (0.1-2.0
      mg kg-1) were below the expected daily nutritional requirement (1-2 mg) for
      humans and pose no toxicological risk. However, catfish from WFP would require
      precautionary measures such as cooking/grilling prior to consumption to avoid
      pathogen infection.

PMID- 29057717
TI  - Craniovertebral fixation ... a new technique of occipital - cervical fixation.
AB  - BACKGROUND: Craniovertebral instability following transoral odontoid excision is
      usually treated by posterior occipital-cervical fixation using occipital plate
      and cervical lateral mass fixation with screw rod construct. A patient previously
      operated for basilar invagination had postoperative infection of both the
      transoral wound and the posterior implant site which needed removal of the
      posterior implant earlier. CLINICAL PRESENTATION: The patient presented with
      severe neck pain, myelopathy, and chronic discharging sinus in the posterior
      lower aspect the previous neck surgery wound. Reimaging revealed incomplete
      odontoid excision. He underwent repeat transoral odontoid excision. Treatment of
      the instability needed occipitocervical fixation avoiding, the atlas, axis
      (weakened by infection and previous implants), and the infected posterior
      cervical wound. A new technique using a customized plate rod construct, fixed
      anteriorly to the mid cervical vertebrae (by a standard mid cervical exposure)
      with the rods contoured to reach posteriorly through the safe paraspinal corridor
      and connected with domino connectors to occipital plate rods fixed on either side
      of midline by additional posterior exposure avoiding the midline scar was planned
      and executed successfully. CONCLUSION: This construct transfers the weight of the
      cranium to the cervical vertebral bodies along the physiological line of weight
      transmission and can be considered for distraction and reduction of basilar
      invagination with atlantoaxial dislocation. The technique seems to be safe and
      reproducible, but will need to tested over time with more cases.

PMID- 29057718
TI  - Escherichia coli genome-scale metabolic gene knockout of lactate dehydrogenase
      (ldhA), increases succinate production from glycerol.
AB  - Genome-scale metabolic model (GEM) of Escherichia coli has been published with
      applications in predicting metabolic engineering capabilities on different carbon
      sources and directing biological discovery. The use of glycerol as an alternative
      carbon source is economically viable in biorefinery. The use of GEM for
      predicting metabolic gene deletion of lactate dehydrogenase (ldhA) for increasing
      succinate production in Escherichia coli from glycerol carbon source remained
      largely unexplored. Here, I hypothesized that metabolic gene knockout of ldhA in
      E. coli from glycerol could increase succinate production. A proof-of-principle
      strain was constructed and designated as E. coli BMS5 (DeltaldhA), by predicting
      increased succinate production in E. coli GEM and confirmed the predicted
      outcomes using wet cell experiments. The mutant GEM (DeltaldhA) predicted 11%
      increase in succinate production from glycerol compared to its wild-type model
      (iAF1260), and the E. coli BMS5 (DeltaldhA) showed 1.05 g/l and its corresponding
      wild-type produced .05 g/l (23-fold increase). The proof-of-principle strain
      constructed in this study confirmed the aforementioned hypothesis and further
      elucidated the fact that E. coli GEM can prospectively and effectively predict
      metabolic engineering interventions using glycerol as substrate and could serve
      as platform for new strain design strategies and biological discovery.

PMID- 29057719
TI  - Changes in gefitinib, erlotinib and osimertinib pharmacokinetics under various
      gastric pH levels following oral administration of omeprazole and vonoprazan in
      rats.
AB  - 1. Although drug interactions between epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs) and gastric acid-suppressing medications (AS) are
      considered clinically significant, there is limited data regarding the influence
      of various gastric pH conditions on the pharmacokinetics of EGFR-TKIs. We aimed
      to clarify the changes in the pharmacokinetics of the EGFR-TKIs, gefitinib,
      erlotinib and osimertinib, due to the changes in gastric pH after administration
      of omeprazole or vonoprazan. 2. Omeprazole (10-100 mg/kg, p.o.) and vonoprazan (1
      5 mg/kg, p.o.) led to a significant and dose-dependent increase in gastric pH. 3.
      AUC0-3 of gefitinib and erlotinib (5 mg/kg, p.o.) started to decrease at gastric
      pH 3.3 and 5.6, respectively, reached a plateau at pH > 6, and then significantly
      decreased up to 47 and 59% of control levels, respectively. AUC0-3 of osimertinib
      (5 mg/kg, p.o.) was not significantly changed by omeprazole and vonoprazan. 4.
      Although there are some issues regarding the extrapolation of the results of our
      rat study to humans, careful monitoring of patients treated with gefitinib and
      erlotinib is needed in cases in which the gastric pH increases from 3 to 5 and
      especially when the gastric pH is >5 in patients who are co-administered both the
      EGFR-TKIs and AS.

PMID- 29057720
TI  - Predictive coding and hallucinations: a question of balance.

PMID- 29057721
TI  - POSH participates in epileptogenesis by increasing the surface expression of the
      NMDA receptor: a promising therapeutic target for epilepsy.
AB  - OBJECTIVES: Plenty of SH3 (POSH) was originally found to be a key regulator of
      neuronal apoptosis, axon outgrowth, and neuronal migration. However, the role of
      POSH in epilepsy has not been reported. METHODS: We investigated the expression
      of POSH in patients with intractable temporal epilepsy (TLE) and in a kainic acid
      (KA)-induced mouse model, and then we performed behavioral, electrophysiological
      and biochemical analyses after the lentivirus (LV)-mediated knockdown or
      overexpression of POSH in the KA-induced model. RESULTS: POSH overexpression
      shortened the latency of seizure onset, increased the frequency of spontaneous
      recurrent seizures, and increased the frequency of electrical epileptic
      discharges, while POSH knockdown had contrasting effects. Whole-cell patch-clamp
      recordings confirmed that POSH overexpression and knockdown were associated with
      increased and decreased miniature excitatory postsynaptic currents (mEPSCs) and N
      methyl-D-aspartate receptor (NMDAR)-mediated currents, respectively. Finally, co
      immunoprecipitation showed that POSH and NMDA receptor subunit 1 (NMDAR1)
      precipitated with each other, and western blot analysis revealed that the surface
      expression of NMDAR1 was altered in the hippocampus of epileptic mice.
      CONCLUSION: These results show that POSH plays a critical role in the progression
      of epileptic seizures via NMDAR trafficking and suggest that the protein is a
      novel target for the treatment of human epilepsy.

PMID- 29057722
TI  - Excessive bodybuilding as pathology? A first neurophysiological classification.
AB  - OBJECTIVES: Excessive bodybuilding as a pathological syndrome has been classified
      based on two different theories: bodybuilding as dependency or as muscle
      dysmorphic disorder (MDD). This study is a first attempt to find
      psychophysiological data supporting one of these classifications. METHODS: Twenty
      four participants (bodybuilders vs healthy controls) were presented with pictures
      of bodies, exercise equipment or general reward stimuli in a control or
      experimental condition, and were measured with functional near-infrared
      spectroscopy (fNIRS). Higher activation in the dorsolateral prefrontal cortex
      (DLPFC) and the orbitofrontal cortex (OFC) while watching bodies and training
      equipment in the experimental condition (muscular bodies and bodybuilding-typical
      equipment) would be an indicator for the addiction theory. Higher activation in
      motion-related areas would be an indicator for the MDD theory. RESULTS: We found
      no task-related differences between the groups in the DLPFC and OFC, but a
      significantly higher activation in bodybuilders in the primary somatosensory
      cortex (PSC) and left-hemispheric supplementary motor area (SMA) while watching
      body pictures (across conditions) as compared to the control group. CONCLUSIONS:
      These neurophysiological results could be interpreted as a first evidence for the
      MDD theory of excessive bodybuilding.

PMID- 29057723
TI  - Treatment effects of phosphodiesterase-5 inhibitors may improve with time
      following nerve-sparing radical prostatectomy.
AB  - OBJECTIVE: Erectile dysfunction (ED) is common following radical prostatectomies,
      and phosphodiesterase type 5 inhibitors (PDE5 inhibitors) are generally
      considered the first choice of treatment. The purpose of this study was to
      analyze the long-term efficacy of PDE5 inhibitors in a group of men who did not
      achieve sufficient erectile function from the medication in the short term
      following surgery. MATERIALS AND METHODS: Prospectively collected data from
      patients with postprostatectomy ED, initial failure of PDE5-inhibitor treatment
      at 3 and/or 6 months and at least 12 months' follow-up were included. All
      patients had completed the International Index of Erectile Function short-form
      questionnaires (IIEF-5) before surgery and at follow-up visits. Response to PDE5
      inhibitors was defined as an IIEF-5 score of at least 17. RESULTS: The inclusion
      criteria were fulfilled by 349 patients. At 12 months, 228 patients were still
      using PDE5 inhibitors. Of these patients, 92 had undergone bilateral and 120 had
      undergone unilateral nerve-sparing radical prostatectomies. Overall, 42 PDE5
      inhibitor users (18%) were responders at 12 months. Bilateral nerve sparing was
      the only independent predictor of a late response (odds ratio = 2.9). Thus, 28%
      of bilaterally nerve-spared patients were responders, while corresponding numbers
      for unilaterally nerve-spared patients and non-nerve-spared patients were 13% and
      6%, respectively. CONCLUSIONS: Patients who have undergone bilateral nerve
      sparing radical prostatectomy should be rechallenged periodically with PDE5
      inhibitors even if the treatment is unsuccessful initially. Unilaterally nerve
      spared patients and especially non-nerve-spared patients are likely to need more
      aggressive treatment.

PMID- 29057724
TI  - Incidence and survival of oropharyngeal cancer in Denmark: a nation-wide,
      population-based study from 1980 to 2014.
AB  - BACKGROUND: Oropharyngeal carcinomas (OPCs) constitute a significant and
      increasing proportion of head and neck carcinomas and are an important global
      cause of morbidity and mortality. The purpose of this study was to determine
      trends in incidence and survival in OPC in the Danish population from 1980 to
      2014. METHODS: This study included all patients registered in the nationwide
      Danish Cancer Registry over the period 1980-2014. The age-adjusted incidence
      rates (AAIR) per 100,000, annual percentage change (APC) and average annual
      percent change (AAPC) were evaluated. Five-year relative survival (RS) was
      calculated with Cox regression analyses in relation to gender, anatomical
      location and histology. RESULTS: A total of 6555 patients (69% male) were
      included, with a median age at diagnosis of 60 years. The AAIR of patients with
      OPC increased from 0.815 per 100,000 in 1980 to 4.51 per 100,000 in 2014 with an
      AAPC of 5.3. The 5-year RS increased significantly from 33.1% over the period
      1980-1984 to 58.5% (25.4% points) over the period 2010-2014. With no significant
      difference stratified for gender. Tumors located at the palatine tonsils (n =
      3333) and salivary gland OPC (n = 90) had significantly better survival compared
      with other sub-locations and histology subtypes. In the APC model the birth
      cohort effect rate ratio increased until 1925 and then decreased until 1935 from
      which point it increased in the last cohorts. CONCLUSIONS: In this population
      based study, we observed a significant increase in the incidence of OPCs and in
      the RS for OPC. We also identified a profound birth cohort effect on the
      incidence.

PMID- 29057725
TI  - Prevalence of Nasal Colonization with Staphylococcus aureus in Patients with
      Rheumatoid Arthritis.
AB  - : Objetive: Patients with Rheumatoid Arthritis (RA) and nasal carriers of
      Staphylococcus aureus have an increased risk of developing infections caused by
      S. aureus. Our objective was to determine the prevalence of S. aureus nasal
      colonization in patients with RA and its relationship to RA treatments. METHODS:
      Two hundred and seven patients with RA and 37 healthy controls were prospectively
      included in a cross-sectional study. A nasal secretion sample was collected by
      swab from both anterior nostrils and was referred to the hospital's microbiology
      department for culturing. RESULTS: The mean age of the patients (168 women, 78%)
      was 61 +/- 12 years old. The mean disease duration was 13 +/- 10 years. Seventy
      six percent of the patients were positive for Rheumatoid Factor (RF), and 71%
      were positive for Anti-citrullinated Peptides Antibodies (ACPA). Seventy percent
      had joint erosions. The mean DAS28 was 3.1 +/- 2.2. S. aureus nasal colonization
      was found in 36% of the RA patients and 35% of the controls. Three patients and
      no controls were resistant to oxacilin/ mupirocin. The patients who were positive
      for ACPA had a higher prevalence of S. aureus colonization (43% vs. 17%; p <
      0.05). The colonization prevalence in the patients treated with glucocorticoids
      was 32% (n: 133); methotrexate and/or leflunomide, 37% (n: 167); anti-TNF agents,
      46% (n: 54), p < 0.05 versus patients not treated with anti-TNF agents;
      rituximab, 22% (n: 18); tocilizumab, 39% (n: 18). CONCLUSION: The prevalence of
      S. aureus nasal colonization in patients with RA does not appear to be greater
      than that of the general population. Anti-TNF agents might confer a higher
      prevalence of colonization.

PMID- 29057726
TI  - [Treatment for acute cholecystitis].
AB  - - This article provides an update on the current state of treatment in respect of
      acute cholecystitis. Several aspects are addressed such as the timing of, and
      approach to, cholecystectomy, the benefits and disadvantages of percutaneous
      gallbladder drainage, conservative treatment and the usefulness of antibiotic
      prophylaxis.- Early cholecystectomy is superior to delayed cholecystectomy as
      this is associated with fewer wound infections, shorter hospital stay, lower
      costs and greater patient satisfaction.- Radiological percutaneous drainage in
      the acute phase of cholecystitis is a procedure with high short-term success
      rates, but it appears to be associated with high rates of recurrent gallstone
      related disease. A Dutch randomized multicentre study is currently investigating
      if high-risk patients benefit most from percutaneous drainage or from early
      cholecystectomy.- Postoperative antibiotic prophylaxis has not been proven useful
      in patients with mild- or moderately-severe acute cholecystitis. The usefulness
      of preoperative antibiotic prophylaxis is currently being studied.

PMID- 29057727
TI  - [Outbreak of Campylobacter fetus infection after consumption of unpasteurized
      sheep's milk cheeses: how to trace the source?]
AB  - Campylobacter fetus is a species of gram-negative bacteria whose primary
      reservoir is the gastrointestinal tracts of cattle and sheep. Human infections
      are rare, though often invasive and sometimes fatal. In this paper, we studied an
      outbreak of six patients with a C. fetus infection and outlined their disease
      histories. In each case we were able to identify factors that led to a reduced
      resistance, including pre-existing illnesses and old age. Because of the
      unusually high number of patients that presented in a time period of only five
      months, the Community Health Services were commissioned to identify the source of
      infection. Using whole genome sequencing, we showed that 5 out of 6 patients
      belonged to the same cluster. This One Health approach resulted in the conclusion
      that the infection originated from unpasteurized sheep's milk processed into
      unripened cheese. Finally, various measures were put into place to prevent any
      further outbreaks.

PMID- 29057728
TI  - [A multidisciplinary approach in diabetic foot disease is mandatory].
AB  - The history of two patients (66- and 53-year-old males) with diabetes and
      peripheral neuropathy illustrates the variety of clinical presentations and
      pitfalls in treatment of diabetic foot ulcers. Peripheral arterial disease and
      mechanical stress as a consequence of peripheral neuropathy are important risk
      factors for developing an ulcer and eventually loss of a limb. Revascularisation
      of the limb should be considered in the presence of critical limb ischaemia or in
      the presence of mild to severe ischaemia in combination with a deep infection.
      Infection is a major threat to the affected limb and requires treatment directly
      after taking samples for culture. After healing, education, adequate offloading
      and frequent foot examinations are important for secondary prevention.
      Presentation of these patients to a special multidisciplinary team, including a
      vascular surgeon, endocrinologist, rehabilitation specialist, cast technician,
      shoe technician and a podiatrist is mandatory, according to the Dutch guidelines
      on the diabetic foot.

PMID- 29057729
TI  - [Optimal duration of antibiotic therapy: there is no 'one size fits all'].
AB  - The increasing use of antibiotics is the main driving force behind the rise of
      antibiotic resistance. Furthermore, there is a large variation in antibiotic use
      amongst prescribers. We describe the current duration of antibiotic therapy for
      common infections in the Netherlands and the new studies we can expect in this
      field in the years to come. We think that more research is needed to determine
      the duration of antibiotic therapy on the basis of different patient
      characteristics. It has, for example, recently been shown that the sex of the
      patient plays an important role in optimal duration of therapy for febrile
      urinary tract infections. Therefore, it is important to identify patients who
      fail on shorter courses of antibiotics in order to avoid overtreatment of all
      patients and to reduce the use of antibiotics in the future.

PMID- 29057730
TI  - [Should we follow the HEART score in patients presenting with chest pain?]
AB  - This article comments on the use of the HEART score as a guide for further
      management in patients presenting with chest pain. Although use of the HEART
      score has been demonstrated to be safe, further research should focus on cost
      effectiveness and outcomes.

PMID- 29057731
TI  - [Research in the GP's practice is good for the health of all].
AB  - The Health Council of the Netherlands has issued a report on the importance of
      extramural medical research. More attention is needed for diseases with high
      prevalence or a high disease burden, and results from intramural research cannot
      always be extrapolated to the primary care setting. Scientific research is
      crucial for developing and evaluating primary health care, so all general
      practitioners (GPs) should at least open their practices to data collection for
      scientific research purposes. Additionally, researchers from departments of
      general practice, together with healthcare professionals, should develop research
      questions that are in line with observed knowledge gaps in general practice. It
      is also important that university medical centres actively support research in
      primary care. A national primary care research agenda could contribute to the
      promotion of GP participation in scientific research in daily practice.

PMID- 29057732
TI  - Effect of systemic immunosuppressive drugs on the patency of hemodialysis
      accesses?.
AB  - AIM: Intimal hyperplasia remains the leading cause of late hemodialysis access
      stenosis or occlusion. This study assessed the influence of conventional
      immunosuppressive drugs on the patency of hemodialysis accesses in patients with
      a history of organ transplantation. MATERIALS AND METHODS: Between January 2002
      and December 2007, 1,654 patients underwent an operation for hemodialysis access.
      135 patients received immunosuppressive therapy (IT); of these, 115 underwent an
      operation for hemodialysis access after transplanted graft failure and 20
      patients after liver transplantation. The 5-year primary patency rates of
      hemodialysis access were compared twice between the entire study population and
      the matched cohorts using a 1 : 4 propensity score. RESULTS: A total of 82.2% of
      the nontransplanted (NT) patients and 71.9% of the IT patients had arteriovenous
      fistulas (AVFs). The 5-year primary patency rate was 74.0% for the NT group and
      51.5% for the IT group (p < 0.001). The characteristics of the matched cohorts
      (135 IT patients and 536 NT patients) were well balanced; the 5-year primary
      patency rates were 70.0% and 54.9% for the NT and IT groups, respectively (p =
      0.030). A significant impact of IT on primary patency was not observed in the
      matched cohort (hazard ratio, 0.930; 95% confidence interval, 0.706 - 0.226; p =
      0.608). CONCLUSION: Systemic administration of immunosuppressive drugs did not
      significantly affect the patency of AVF or arteriovenous graft (AVG) access in
      the present study.?.

PMID- 29057733
TI  - Membranoproliferative glomerulonephritis with unusual deposits of parallel
      arrangement striated structure: a new pathological entity??.
AB  - A 71-year-old male with a past history of lower limb arteriosclerosis obliterans
      developed nephrotic syndrome and renal dysfunction. Renal biopsy showed diffuse
      global endocapillary proliferative lesions with infiltration of mononuclear cells
      and occasional foam cells. An irregular double contour of the glomerular basement
      membrane and global mild-to-moderate mesangial proliferative lesions were
      observed, indicating membranoproliferative glomerulonephritis. Congo red staining
      was negative. Routine immunofluorescence studies showed no obvious immunoglobulin
      or complement depositions. Electron microscopy showed endocapillary proliferative
      lesions and infiltration of macrophages with abundant lysosomes. Irregular
      subepithelial, subendothelial, and mesangial electron-dense deposits were
      observed in glomeruli. In these electron-dense deposits, parallel arrangement
      striated structures were detected. All known disease entities with Congo red
      negative and immunoglobulin-negative glomerular deposits were pathologically
      excluded. The glomerular lesion in our case might be a new disease entity.?.

PMID- 29057734
TI  - Provider perspectives on chronic kidney disease diagnosis delivery?.
AB  - AIMS: Lack of clear provider communication has been suggested as a reason for low
      patient awareness of their chronic kidney disease (CKD) diagnosis. Using quality
      improvement methods, we performed one-on-one provider interviews about CKD
      diagnosis delivery. MATERIALS AND METHODS: Interviews were audio-recorded,
      transcribed, and examined using mixed methods. We used thematic analysis to code
      and analyze transcripts, and Fisher's exact test to examine differences comparing
      nephrologist and primary care provider (PCP) perspectives. RESULTS: 24 providers
      completed interviews (18 nephrologists, 6 PCPs). Four themes emerged (N = 260
      statements): 1) perspectives informing patients about CKD diagnosis (37
      statements), 2) timing of diagnosis messaging (38 statements), 3) language used
      to convey diagnosis (42 statements), and 4) challenges in diagnosis delivery (143
      statements). Most agreed that patients should be informed of their CKD (87.5%),
      but only 76% believed that communication should occur early. Terminology was not
      unified; half of nephrology providers used the term "Chronic Kidney Disease" to
      explain diagnosis. No PCPs used this terminology. Challenges to CKD diagnosis
      delivery included: Kidney disease is perceived as difficult to explain, lack of
      provider time, lack of patient symptoms, patient denial of disease, and low
      public awareness of CKD. CONCLUSIONS: Providers' views on informing patients of
      their CKD diagnosis were not unified, in particular with respect to timing and
      terminology of diagnosis delivery. More work is needed to address barriers to
      efficiently and effectively convey CKD diagnosis information.?.

PMID- 29057736
TI  - Mycobacterium paragordonae: a rare cause of peritonitis in a peritoneal dialysis
      patient.

PMID- 29057735
TI  - Association between chronic kidney disease and the cognitive function in subjects
      without overt dementia?.
AB  - AIM: The association between cognitive function and clinical parameters of
      chronic kidney disease (CKD) was investigated in Japanese patients without overt
      dementia in a cross-sectional study. MATERIALS AND METHODS: A population of 497
      patients whose cognitive function had been examined using the mini-mental state
      examination (MMSE) were screened for this study. After the exclusion of 306
      subjects who showed overt dementia, the association between the MMSE score and
      clinical characteristics was investigated in 191 subjects (male: 55%, age: 69 +/-
      12 years). RESULTS: The mean MMSE score of the study subjects was 26.7 +/- 2.0.
      The MMSE score was negatively correlated with the patients' age and positively
      with the estimated glomerular filtration rate. It was significantly associated
      with age and proteinuria based on a multivariate analysis. The scores of
      "temporal orientation", "attention and calculation", and "remote memory" subitems
      of MMSE were significantly lower in the subjects >= 70 years of age than in those
      < 70 years of age. The scores of "temporal orientation" (4.3 +/- 0.8 vs. 4.7 +/-
      0.6), "attention and calculation" (2.9 +/- 1.6 vs. 3.9 +/- 1.5), and "stage
      command" (2.7 +/- 0.5 vs. 2.9 +/- 0.3) were significantly lower in the subjects
      with proteinuria than in those without. CONCLUSION: Cognitive function was
      disturbed even in CKD patients without overt dementia. Intervention in patients
      with risk factors is deemed important for preventing future reductions in
      cognitive and renal functions in CKD patients without dementia.?.

PMID- 29057737
TI  - Bovine Amniotic Fluid: A New and Occupational Source of Galactose-alpha-1,3
      Galactose.

PMID- 29057738
TI  - Chemotherapy in Mastocytosis: Administration Issues, Hypersensitivity, and Rapid
      Drug Desensitization.

PMID- 29057739
TI  - Protein Contact Dermatitis to Chrysanthemum.

PMID- 29057740
TI  - Reversible Hypogammaglobulinemia in 2 Pediatric Patients With Primary
      Immunodeficiency.

PMID- 29057741
TI  - Pregnancy and Postpartum in Hereditary Angioedema With C1 Inhibitor Deficit in
      Women Who Have No Access to Therapy.

PMID- 29057742
TI  - Fixed Eruption by Multiple Plant Foods.

PMID- 29057743
TI  - Omalizumab as Third-Line Therapy for Urticaria During Pregnancy.

PMID- 29057744
TI  - Acute Localized Exanthematous Pustulosis Due to Bemiparin.

PMID- 29057745
TI  - Palpebral Edema and Eosinophilia.

PMID- 29057746
TI  - Scoliid Wasp Sting: A New Cause of Anaphylaxis.

PMID- 29057747
TI  - Initial False-Negative Specific IgE to Gelatin in Gelatin-Induced Anaphylaxis.

PMID- 29057748
TI  - Dosimetry and prescription in liver radioembolization with 90Y microspheres: 3D
      calculation of tumor-to-liver ratio from global 99mTc-MAA SPECT information.
AB  - Dosimetry in liver radioembolization with 90Y microspheres is a fundamental tool,
      both for the optimization of each treatment and for improving knowledge of the
      treatment effects in the tissues. Different options are available for estimating
      the administered activity and the tumor/organ dose, among them the so-called
      partition method. The key factor in the partition method is the tumor/normal
      tissue activity uptake ratio (T/N), which is obtained by a single-photon emission
      computed tomography (SPECT) scan during a pre-treatment simulation. The less
      clear the distinction between healthy and tumor parenchyma within the liver, the
      more difficult it becomes to estimate the T/N ratio; therefore the use of the
      method is limited. This study presents a methodology to calculate the T/N ratio
      using global information from the SPECT. The T/N ratio is estimated by
      establishing uptake thresholds consistent with previously performed volumetry.
      This dose calculation method was validated against 3D voxel dosimetry, and was
      also compared with the standard partition method based on freehand regions of
      interest (ROI) outlining on SPECT slices. Both comparisons were done on a sample
      of 20 actual cases of hepatocellular carcinoma treated with resin microspheres.
      The proposed method and the voxel dosimetry method yield similar results, while
      the ROI-based method tends to over-estimate the dose to normal tissues. In
      addition, the variability associated with the ROI-based method is more extreme
      than the other methods. The proposed method is simpler than either the ROI or
      voxel dosimetry approaches and avoids the subjectivity associated with the manual
      selection of regions.

PMID- 29057749
TI  - CoFeB/MgO/CoFeB structures with orthogonal easy axes: perpendicular anisotropy
      and damping.
AB  - We report on the Gilbert damping parameter alpha, the effective magnetization
      [Formula: see text], and the asymmetry of the g-factor in bottom-CoFeB(0.93
      nm)/MgO(0.90-1.25 nm)/CoFeB(1.31 nm)-top as-deposited systems. Magnetization of
      CoFeB layers exhibits a specific noncollinear configuration with orthogonal easy
      axes and with [Formula: see text] values of [Formula: see text] kG and [Formula:
      see text] kG for the bottom and top layers, respectively. We show that [Formula:
      see text] depends on the asymmetry [Formula: see text] of the g-factor measured
      in the perpendicular and the in-plane directions revealing a highly nonlinear
      relationship. In contrast, the Gilbert damping is practically the same for both
      layers. Annealing of the films results in collinear easy axes perpendicular to
      the plane for both layers. However, the linewidth is strongly increased due to
      enhanced inhomogeneous broadening.

PMID- 29057750
TI  - Moisture effect on interfacial integrity of epoxy-bonded system: a hierarchical
      approach.
AB  - The epoxy-bonded system has been widely used in various applications across
      different scale lengths. Prior investigations have indicated that the moisture
      affected interfacial debonding is the major failure mode of such a system, but
      the fundamental mechanism remains unknown, such as the basis for the invasion of
      water molecules in the cross-linked epoxy and the epoxy-bonded interface. This
      prevents us from predicting the long-term performance of the epoxy-related
      applications under the effect of the moisture. Here, we use full atomistic models
      to investigate the response of the epoxy-bonded system towards the adhesion test,
      and provide a detailed analysis of the interfacial integrity under the moisture
      effect and the associated debonding mechanism. Molecular dynamics simulations
      show that water molecules affect the hierarchical structure of the epoxy-bonded
      system at the nanoscale by disrupting the film-substrate interaction and the
      molecular interaction within the epoxy, which leads to the detachment of the
      epoxy thin film, and the final interfacial debonding. The simulation results show
      good agreement with the experimental results of the epoxy-bonded system. Through
      identifying the relationship between the epoxy structure and the debonding
      mechanism at multiple scales, it is shown that the hierarchical structure of the
      epoxy-bonded system is crucial for the interfacial integrity. In particular, the
      available space of the epoxy-bonded system, which consists of various sizes
      ranging from the atomistic scale to the macroscale and is close to the interface
      facilitates the moisture accumulation, leading to a distinct interfacial
      debonding when compared to the dry scenario.

PMID- 29057751
TI  - Chemical states of surface oxygen during CO oxidation on Pt(1 1 0) surface
      revealed by ambient pressure XPS.
AB  - The study of CO oxidation on Pt(1 1 0) surface is revisited using ambient
      pressure x-ray photoemission spectroscopy. When the surface temperature reaches
      the activation temperature for CO oxidation under elevated pressure conditions,
      both the alpha-phase of PtO2 oxide and chemisorbed oxygen are formed
      simultaneously on the surface. Due to the exothermic nature of CO oxidation, the
      temperature of the Pt surface increases as CO oxidation takes place. As the CO/O2
      ratio increases, the production of CO2 increases continuously and the surface
      temperature also increases. Interestingly, within the diffusion limited regions,
      the amount of surface oxide changes little while the chemisorbed oxygen is
      reduced.

PMID- 29057752
TI  - Ab initio simulations of water splitting on hematite.
AB  - In recent years, hematite has attracted great interest as a photocatalyst for
      water splitting, but many questions remain unanswered about the mechanisms and
      the main limiting factors. For this reason, density functional theory has been
      used to understand the optical, electronic and chemical properties of this
      material at an atomistic level. Bulk doping can be used to reduce the band gap,
      and to increase photoabsorption and charge mobility. Charge transport takes place
      through adiabatic polaron hopping. The stable (0 0 0 1) surface has a
      stoichiometric termination when exposed to oxygen, it becomes hydroxylated in
      water, and it has an oxygen-rich termination under illumination in a
      photoelectrochemical setup. On the oxygen-rich termination, surface states are
      present that might act as recombination centres for electrons and holes. On the
      contrary, on the hydroxylated termination surface states appear only on reaction
      intermediates. The intrinsic surface states disappear in the presence of an
      overlayer of gallium oxide. The reaction of water oxidation is assumed to proceed
      by four proton-coupled electron transfers and it is shown to involve a
      nucleophilic attack with the formation of an OOH group. Calculated overpotentials
      are in the range of 0.5-0.6 V. Open questions and future research directions are
      briefly discussed.

PMID- 29057753
TI  - Validation of proton stopping power ratio estimation based on dual energy CT
      using fresh tissue samples.
AB  - Dual energy CT (DECT) has been shown, in theoretical and phantom studies, to
      improve the stopping power ratio (SPR) determination used for proton treatment
      planning compared to the use of single energy CT (SECT). However, it has not been
      shown that this also extends to organic tissues. The purpose of this study was
      therefore to investigate the accuracy of SPR estimation for fresh pork and beef
      tissue samples used as surrogates of human tissues. The reference SPRs for
      fourteen tissue samples, which included fat, muscle and femur bone, were measured
      using proton pencil beams. The tissue samples were subsequently CT scanned using
      four different scanners with different dual energy acquisition modes, giving in
      total six DECT-based SPR estimations for each sample. The SPR was estimated using
      a proprietary algorithm (syngo.via DE Rho/Z Maps, Siemens Healthcare, Forchheim,
      Germany) for extracting the electron density and the effective atomic number.
      SECT images were also acquired and SECT-based SPR estimations were performed
      using a clinical Hounsfield look-up table. The mean and standard deviation of the
      SPR over large volume-of-interests were calculated. For the six different DECT
      acquisition methods, the root-mean-square errors (RMSEs) for the SPR estimates
      over all tissue samples were between 0.9% and 1.5%. For the SECT-based SPR
      estimation the RMSE was 2.8%. For one DECT acquisition method, a positive bias
      was seen in the SPR estimates, having a mean error of 1.3%. The largest errors
      were found in the very dense cortical bone from a beef femur. This study confirms
      the advantages of DECT-based SPR estimation although good results were also
      obtained using SECT for most tissues.

PMID- 29057754
TI  - In situ passivation of GaAsP nanowires.
AB  - We report on the structural and optical properties of GaAsP nanowires (NWs) grown
      by molecular-beam epitaxy. By adjusting the alloy composition in the NWs, the
      transition energy was tuned to the optimal value required for tandem III
      V/silicon solar cells. We discovered that an unintentional shell was also formed
      during the GaAsP NW growth. The NW surface was passivated by an in situ
      deposition of a radial Ga(As)P shell. Different shell compositions and
      thicknesses were investigated. We demonstrate that the optimal passivation
      conditions for GaAsP NWs (with a gap of 1.78 eV) are obtained with a 5 nm thick
      GaP shell. This passivation enhances the luminescence intensity of the NWs by 2
      orders of magnitude and yields a longer luminescence decay. The luminescence
      dynamics changes from single exponential decay with a 4 ps characteristic time in
      non-passivated NWs to a bi-exponential decay with characteristic times of 85 and
      540 ps in NWs with GaP shell passivation.

PMID- 29057755
TI  - Graphene-oxide-wrapped ZnMn2O4 as a high performance lithium-ion battery anode.
AB  - Cation distribution between tetrahedral and octahedral sites within the ZnMn2O4
      spinel lattice, along with microstructural features, is affected greatly by the
      temperature of heat treatment. Inversion parameters can easily be tuned, from 5%
      19%, depending on the annealing temperature. The upper limit of inversion is
      found for T = 400  degrees C as confirmed by x-ray powder diffraction and Raman
      spectroscopy. Excellent battery behavior is found for samples annealed at lower
      temperatures; after 500 cycles the specific capacity for as-prepared ZnMn2O4 is
      909 mAh g-1, while ZnMn2O4 heat-treated at 300  degrees C is 1179 mAh g-1, which
      amounts to 101% of its initial capacity. Despite the excellent performance of a
      sample processed at 300  degrees C at lower charge/discharge rates (100 mAh g-1),
      a drop in the specific capacity is observed with rate increase. This issue is
      solved by graphene-oxide wrapping: the specific capacity obtained after the 400th
      cycle for graphene-oxide-wrapped ZnMn2O4 heat-treated at 300  degrees C is 799
      mAh g-1 at a charge/discharge rate 0.5 A g-1, which is higher by a factor of 6
      compared to samples without graphene -oxide wrapping.

PMID- 29057756
TI  - A systematic study of 4d and 5d transition metal mediated exchange coupling
      between Fe and Gd nanolaminates.
AB  - We present a systematic study of the magnetic coupling between iron and
      gadolinium layers intermediated by 4d and 5d transition metals using density
      functional theory. We demonstrate that it is possible to find a magnetic coupling
      for most of them. In particular, for the early transition metals (d 1, d 2, d 3
      and d 4), a ferromagnetic coupling occurs even stronger than the 3d interlayers.
      Atomic size and the electronic configuration of the transition metals are crucial
      for the nature of the coupling. All the open shell transition metals present
      induced magnetic moments. By increasing the number of interlayers, an oscillating
      behavior in the magnetic coupling was found and the magnetic coupling goes to
      zero beyond four spacer layers. Using Monte Carlo simulations, we demonstrate
      that the interlayer strongly enhances the critical temperature in the Gd layers
      closest to the interface.

PMID- 29057757
TI  - Large-area and highly crystalline MoSe2 for optical modulator.
AB  - Transition metal dichalcogenides (TMDs) have been successfully used as broadband
      optical modulator materials for pulsed fiber laser systems. However, the
      nonlinear optical absorptions of exfoliated TMDs are strongly limited by their
      nanoflakes morphology with uncontrollable lateral size and thickness. In this
      work, we provide an effective method to fully explore the nonlinear optical
      properties of MoSe2. Large-area and high quality lattice MoSe2 grown by chemical
      vapor deposition method was adopted as an optical modulator for the first time.
      The large-area MoSe2 shows excellent nonlinear optical absorption with a large
      modulation depth of 21.7% and small saturable intensity of 9.4 MW cm-2. After
      incorporating the MoSe2 optical modulator into fiber laser cavity as a saturable
      absorber, a highly stable Q-switching operation with single pulse energy of 224
      nJ is achieved. The large-area MoSe2 possessing superior nonlinear optical
      properties compared to exfoliated nanoflakes affords possibility for the larger
      area two-dimensional materials family as high performance optical devices.

PMID- 29057758
TI  - Ovarian lesions in 44 rabbits (Oryctolagus cuniculus).
AB  - The clinical and pathological records of 44 domestic, female rabbits with an age
      ranging from 6-124 months (median age: 63.5 month) were assessed retrospectively
      for ovarian lesions. Included were all rabbits that underwent an
      ovariohysterectomy with a subsequent pathological examination of the genital
      tract between March 1997 and June 2016. Pathological examination revealed ovarian
      lesions in 12 of the 44 rabbits including follicular cysts (n=7), cystic rete
      ovarii (n=3), widespread ovarian necrosis with dystrophic calcification (n=2),
      ovarian adenoma (n=1). Clinical examination including radiographs only suggested
      ovarian disorders in two cases of ovarian necrosis with dystrophic calcification
      and in two cases of cystic rete ovarii. Clinical significance was only conclusive
      in a case of cystic rete ovarii.

PMID- 29057759
TI  - Novel Cadaver Injection Method Using Latex and Magnetic Fluid.
AB  - Vascular injection into extracted tissue may be associated with leakage due to
      excessive local injection pressure. Historically, this complication has been
      impossible to resolve because the injection pressure has been the only available
      force with which to send the agent to the peripheral vasculature. We have
      developed a new vascular injection method that utilizes a material affected by
      magnetic force and is therefore not solely dependent upon the injection pressure.
      We mixed the same weights of latex and magnetic fluid and injected the solution
      into the arterial stump of an extracted tissue specimen. Next, we used a
      permanent magnet to attract the agent into the peripheral vasculature. We
      repeated the injection and magnetic application until no further fluid could be
      injected. We used this method in 20 formalin-fixed tissue specimens. The vessels
      were clearly observable through to the peripheral areas, and leakage from the
      injected artery was minimal. This new agent has several beneficial
      characteristics: it is X-ray impermeable, is durable in the face of chemical
      insult, and allows for easy visual observation. The injected tissue can be
      studied for X-ray film examination, tissue clarification, and gross anatomical
      dissection. Additionally, this method can be applied to both fresh and formalin
      fixed tissue. We consider that this method has the potential to expand the
      applications of injection studies.

PMID- 29057760
TI  - Anaplastic Thyroid Carcinoma Treated with Lenvatinib.
AB  - OBJECTIVE: We report a case of anaplastic thyroid carcinoma (ATC) with local
      recurrence and distant metastasis that responded very well to treatment with
      lenvatinib, a new molecular-targeted anticancer drug. CASE REPORT: A 91-year-old
      Japanese woman presented with a 5-month history of a painless mass in her left
      anterior neck. She had a past history of total thyroidectomy and neck dissection
      for papillary carcinoma of the thyroid. Here she underwent neck dissection, and
      the histopathological diagnosis was lymph node metastasis of papillary carcinoma
      with anaplastic transformation. Five months later, a cervical lymph node swelled
      up again. Computed tomography demonstrated an enhanced mass in the neck and
      multiple nodules in both lungs. Recurrent ATC with multiple lung metastases was
      diagnosed, and molecular-targeted therapy with lenvatinib was initiated. The neck
      tumor reduced in 1 week, and the pulmonary nodules became completely hollow
      within 1 month. However, we had to discontinue lenvatinib because of severe side
      effects including high blood pressure, hypocalcemia, and hypoalbuminemia. Soon
      after discontinuation, the side effects subsided, but the tumor rapidly regrew.
      The patient died of lymphangiosis carcinomatosa 6 days after discontinuation.
      CONCLUSION: Although recent advances in molecular-targeted therapy have provided
      powerful cancer therapy tools, the negative side of this therapy must be
      addressed.

PMID- 29057761
TI  - Social Network Structure and Atherosclerotic Cardiovascular Disease.

PMID- 29057763
TI  - Vasohibin-1 Is a Poor Prognostic Factor of Ovarian Carcinoma.
AB  - Vasohibin-1 (VASH1) is an identified negative feedback inhibitor of angiogenesis
      induced by vascular endothelial growth factor (VEGF) in vascular endothelial
      cells (ECs). Expression of VASH1 has been reported not only in ECs of normal
      tissue, but also in ECs surrounding malignant tumors. In malignant tumors, VASH1
      is also gaining attention as a prognosis prediction marker. The aim of this study
      is to investigate the correlation between VASH1 expression and vascular-related
      factors and various clinicopathological outcomes in clinical cases of ovarian
      carcinoma. We retrospectively analyzed clinical records of 58 patients with
      ovarian carcinoma. The expression patterns of VASH1 and other vascular-related
      factors (CD31 as markers of microvessel density (MVD), VEGF receptor type 2
      (VEGFR2), D2-40 as markers of lymphovessel density), and Ki67 (as proliferation
      markers of cancer cells) were examined immunohistochemically. We studied the
      correlation between immunohistochemical expression and overall survival. VASH1
      expression pattern significantly differed between Federation of Obstetrics and
      Gynecology (FIGO) Stages. Numbers of VASH1-positive vessels had a significant
      positive correlation with MVD (Speaman's correlation coefficient (rho) was 0.51,
      p < 0.001), VEGFR2-positive vessels (rho = 0.61, p < 0.001), and percentage of
      Ki67 (rho = 0.28, p = 0.034). The Cox univariable analyses revealed that the
      group of high VASH1 expression (> 14.6 vessels per mm2) at Stages I-III is a
      prognostic factor (HR = 3.3, 95%CI = 0.4-8.4; p = 0.013). Our results indicate
      that VASH1 expression in ovarian carcinoma is significantly associated with
      vascular-related factors and Ki67 expression. We propose that VASH1 is a
      prognostic marker in ovarian carcinoma.

PMID- 29057762
TI  - Fluctuations in heart rate variability of health care workers during four
      consecutive extended work shifts and recovery during rest and sleep.
AB  - The aim of this study was to investigate fluctuations in heart rate variability
      (HRV), which reflect autonomic nervous system (ANS) function and potential
      psychological and physical strain, among 24 health care workers during work and
      sleep during four consecutive extended work shifts. Data included 24/36/12 h of
      HRV measurements, two logbooks, and a questionnaire. A cross-shift/cross-week
      design was applied. HRV was measured during work, leisure time, and sleep. The
      HRV data included time-domain [mean RR, SD of normal to normal R-R intervals
      (SDNN), and root mean square of the successive differences (RMSSD)] and frequency
      domain [low frequency (LF)/high frequency (HF) ratio] parameters. HRV parameters
      revealed significant differences among work, leisure time, and sleep. Mean RR,
      RMSSD, and SDNN values were lower and the LF/HF ratio was higher on the first
      versus last day of the work period; however, the differences were most prominent
      in the morning hours. The results indicate higher levels of cardiovascular stress
      on the first versus fourth day of the working period, and measurements at night
      indicate a satisfactory recovery from the extended shifts.

PMID- 29057764
TI  - Evaluation of total intravenous anesthesia with propofol-guaifenesin-medetomidine
      and alfaxalone-guaifenesin-medetomidine in Thoroughbred horses undergoing
      castration.
AB  - Anesthetic and cardiorespiratory effects of total intravenous anesthesia (TIVA)
      technique using propofol-guaifenesin-medetomidine (PGM) and alfaxalone
      guaifenesin-medetomidine (AGM) were preliminarily evaluated in Thoroughbred
      horses undergoing castration. Twelve male Thoroughbred horses were assigned
      randomly into two groups. After premedication with intravenous (IV)
      administrations of medetomidine (5.0 ug/kg) and butorphanol (0.02 mg/kg),
      anesthesia was induced with guaifenesin (10 mg/kg IV), followed by either
      propofol (2.0 mg/kg IV) (group PGM: n=6) or alfaxalone (1.0 mg/kg IV) (group AGM:
      n=6). Surgical anesthesia was maintained for 60 min at a constant infusion of
      either propofol (3.0 mg/kg/hr) (group PGM) or alfaxalone (1.5 mg/kg/hr) (group
      AGM), in combination with guaifenesin (80 mg/kg/hr) and medetomidine (3.0
      ug/kg/hr). Responses to surgical stimuli, cardiorespiratory values, and induction
      and recovery characteristics were recorded throughout anesthesia. During
      anesthesia induction, one horse paddled in group PGM. All horses from group AGM
      were maintained at adequate anesthetic depth for castration. In group PGM, 3
      horses showed increased cremaster muscle tension and one showed slight movement
      requiring additional IV propofol to maintain surgical anesthesia. No horse
      exhibited apnea, although arterial oxygen tension decreased in group AGM to less
      than 60 mmHg. Recovery quality was good to excellent in both groups. In
      conclusion, TIVA using PGM and AGM infusion was available for 60 min anesthesia
      in Thoroughbred horses. TIVA techniques using PGM and AGM infusion provided
      clinically acceptable general anesthesia with mild cardiorespiratory depression.
      However, inspired air should be supplemented with oxygen to prevent hypoxemia
      during anesthesia.

PMID- 29057766
TI  - Clinical Results, Adverse Events, and Change in End-Organ Function in Elderly
      Patients With HeartMateII Left Ventricular Assist Device - Japanese Multicenter
      Study.
AB  - BACKGROUND: Advanced age has an adverse impact on clinical results in left
      ventricular assist device (LVAD) patients. We compared the clinical results of
      patients aged >60 years with younger patients using a national Japanese
      database.Methods and Results:Between April 2013 and December 2016, 300 patients
      underwent HeartMateII implantation. Of these, 37 patients were >=60 years at LVAD
      implantation, and the clinical results of these patients were compared with the
      other younger 263 patients. At 1 and 3 years the on-device survival was 95%, 91%
      in younger patients, and 85%, 75% in older patients, respectively (P=0.016),
      although age was not a risk factor on the multivariate analysis. There was no
      significant difference between the groups in incidence of various adverse events
      except stroke. In the propensity-matching cohort, the incidence of stroke was
      significantly higher in patients aged >60 years (P=0.047). In patients aged >60
      years, improvement of renal function was transient and there was no improvement
      later than 3 months, and recovery of serum albumin level to preoperative value
      was delayed. CONCLUSIONS: There were significant differences in the stroke
      incidence and recovery of end-organ functions after LVAD implantation. This may
      have important implications for patient selection in future destination therapy
      in Japan, where quality of life is an important issue in LVAD support.

PMID- 29057765
TI  - Development of LAMP assays for the molecular detection of taeniid infection in
      canine in Tibetan rural area.
AB  - For field-identification of taeniid cestodes in canine animals in Tibetan area,
      loop-mediated isothermal amplification (LAMP) assays for Echinococcus
      multilocularis, E. shiquicus, Taenia hydatigena, T. multiceps, T. pisiformis and
      T. crassiceps were developed and evaluated along with the reported assay for E.
      granulosus. The LAMP assays showed specific reaction with their corresponding
      target species DNA with the detection limit of 1 to 10 pg. Moreover, the assays
      for E. granulosus, E. multilocularis, T. hydatigena and T. multiceps could detect
      DNA extracted from 3 or more eggs of their corresponding target species. Then,
      the LAMP assays were applied on samples containing 3 to 35 taeniid eggs obtained
      from 61 field-collected canine feces in Qinghai, and the result was compared with
      a reported multiplex PCR and sequence analysis. The LAMP assays and the PCR
      detected single species DNA of E. granulosus, E. shiquicus, T. hydatigena and T.
      multiceps in 5, 2, 44 and 2 samples, respectively. In the rest 8 samples, DNA of
      both E. granulosus and T. hydatigena were detected by the PCR but the LAMP assays
      detected those DNAs in 2 samples and only T. hydatigena DNA in 6 samples. It was
      assumed that less than 3 E. granulosus eggs were mixed in the samples although
      the samples contained 21 to 27 eggs in total. In conclusion, the LAMP assays were
      less sensitive than the multiplex PCR, but would have adequate sensitivity for
      field use in Tibetan area.

PMID- 29057767
TI  - Embryogenesis of vitrified mature bovine oocytes is improved in the presence of
      multi-layered cumulus cells.
AB  - This study was aimed at evaluating the effects of multi-layered cumulus cells
      (MCCs) during vitrification and in vitro fertilization (IVF) of mature bovine
      oocytes and embryogenesis after IVF. The rates of cleavage and blastocyst
      formation were higher in vitrified and fertilized oocytes with MCCs than in
      denuded oocytes (P < 0.05), but were comparable to the rates in fresh oocytes
      with MCCs or without (denuded). When the MCC-enclosed oocytes were denuded before
      IVF, blastocyst formation rate reduced compared with that in vitrified oocytes
      with MCCs (P < 0.05). This suggested that the MCCs surrounding the mature bovine
      oocytes play important roles during cryopreservation: protecting them against
      freezing and promoting their survival and development post IVF, thereby
      increasing the success rates of IVF and embryonic development. Herein, we showed
      for the first time that calves could be produced using only 14-19 vitrified
      mature oocytes with MCCs from the ovaries of individual cows post slaughter.

PMID- 29057768
TI  - Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy
      during oxygen-glucose deprivation.
AB  - Ghrelin functions as a neuroprotective agent and saves neurons from various
      insults include ischemic injury. However, it remains to be elucidated whether
      ghrelin protects neuronal cells against ischemic injury-induced excessive
      autophagy. Autophagy is required for the maintenance of neural stem cell
      homeostasis. However, regarding autophagic cell death, it is commonly assumed
      that excessive autophagy leads to self-elimination of mammalian cells. The
      purpose of this study was to investigate the potential neuroprotection effects of
      ghrelin from excessive autophagy in adult rat hippocampal neural stem cells
      (NSCs). Oxygen-Glucose Deprivation (OGD) strongly induces autophagy in adult rat
      hippocampal NSCs. Ghrelin treatment inhibited OGD-induced cell death of adult rat
      hippocampal NSCs assessed by cell-counting-kit-8 assay. Ghrelin also suppressed
      OGD-induced excessive autophagy activity. The protective effect of ghrelin was
      accompanied by an increased expression levels of Bcl-2, p-62 and decreased
      expression level of LC3-II, Beclin-1 by Western blot. Furthermore, ghrelin
      reduced autophagosome formation and number of GFP-LC3 transfected puncta. In
      conclusion, our data suggest that ghrelin protects adult rat hippocampal NSCs
      from excessive autophagy in experimental stroke (oxygen-glucose deprivation)
      model. Regulating autophagic activity may be a potential optimizing target for
      promoting adult rat hippocampal NSCs based therapy for stroke.

PMID- 29057769
TI  - Exploring how a traditional diluted yoghurt drink may mitigate heat strain during
      medium-intensity intermittent work: a multidisciplinary study of occupational
      heat strain.
AB  - It is common practice in India to consume the dairy drink buttermilk as a way of
      mitigating occupational heat strain. This paper explores the thermoregulatory and
      hydration benefits of drinking buttermilk but also the impacts of work in a hot
      environment on the gut microbiota, renal and cognitive function. Twelve healthy
      participants were subjected to a 3-h period of medium load physical intermittent
      work in a climatic chamber (34 degrees C, 60% RH). The subjects were given water,
      buttermilk (700 ml) or no rehydration at random. Mean body temperatures when no
      rehydration was given were significantly higher (p<=0.001). When subjects drank
      water or buttermilk they had a lower sweat rate than with no rehydration
      (p<=0.05) and the perception of feeling hot, uncomfortable, thirsty and
      physically exerted was significantly reduced (p<=0.05). A hormonal stress
      response at the end of the exposure was seen when not drinking (p<=0.05). No
      differences in cognitive abilities and gut microbiota were found. The exposure
      lowered the renal blood flow suggesting an acute impact of short term heat
      exposure. It was also found that buttermilk has a protective effect on this
      impact. Our results demonstrated that keeping hydrated by water/buttermilk
      consumption mitigates heat strain in well-nourished subjects.

PMID- 29057770
TI  - Iatrogenic Aortic Valve Perforation after Ventricular Septal Defect Repair.
AB  - Iatrogenic aortic valve (AV) perforation during non-aortic cardiac operations is
      a rare complication. The suture-related inadvertent injury to an AV leaflet can
      produce leaflet perforation with aortic regurgitation after ventricular septal
      defect repair (VSDR). We report three consecutive patients who had iatrogenic
      aortic leaflet perforation during VSDR in other hospitals and referred to our
      hospital for reoperation. In all three cases, the perforated AV leaflets were
      preserved and repaired by autologous pericardial patch or direct local closure.

PMID- 29057771
TI  - Impact of Serum Phosphorus Levels on Outcomes After Implantation of Drug-Eluting
      Stents in Patients on Hemodialysis.
AB  - BACKGROUND: Elevated serum phosphorus level is an important risk factor for
      cardiovascular death in general patients on hemodialysis (HD). However, the
      effect of serum phosphorus levels on outcomes after drug-eluting stent (DES)
      implantation in HD patients is unknown.Methods and Results:This was a post-hoc
      study of the OUCH study series, a series of prospective multicenter registries of
      HD patients who underwent DES implantation comprising 359 patients from 31
      centers in Japan. Patients were categorized into 3 groups according to their
      preprocedural serum phosphorus levels. The 1-year clinical outcomes of the 336
      patients treated for de novo lesions were evaluated. Compared with patients with
      high (>5.5 mg/dL; n=65) or normal (3.5-5.5 mg/dL; n=219) serum phosphorus levels,
      those with low serum phosphorus levels (<3.5 mg/dL; n=52) had significantly fewer
      target lesion revascularization events (13.9% vs. 16.9% vs. 1.9%; P=0.0090) and
      major adverse cardiac and cerebrovascular events (29.2% vs. 31.1% vs. 13.5%;
      P=0.032). Multivariate logistic regression analysis revealed that low serum
      phosphorus level was an independent negative predictor for major adverse cardiac
      and cerebrovascular events (adjusted odds ratio, 0.31; 95% confidence interval,
      0.12-0.70; P=0.0036). CONCLUSIONS: Lowering of serum phosphorus levels beyond the
      current recommended range may be considered in HD patients who undergo DES
      implantation.

PMID- 29057772
TI  - Investigation of the Section Thickness Measurement in Tomosynthesis by Thin Metal
      Plate Edge Method.
AB  - When performing tomosynthesis, the section thickness needs to be set depending on
      a radiographic part and its diagnostic purpose. However, the section thickness in
      tomosynthesis has not been clearly defined and its measurement method has not
      been established yet. In this study, we devised the alternative measurement
      method to diagnose the section thickness using an edge of thin metal plate, and
      compared with the simulation results, the wire and bead method reported in the
      previous papers. The tomographic image of the thin metal plate positioned on the
      table top inclining 30 degrees, which showed the edge spread function (ESF) of
      each tomographic height, was taken, and then the line spread function (LSF) was
      obtained by differentiating the ESF image. For the next, a profile curve was
      plotted by maximum values of LSF of each tomographic height, and a section
      thickness was calculated using the full width at half maximum (FWHM) of the
      profile curve. The edge method derived the section thickness close to the
      simulation results than the other methods. Further, the section thickness depends
      on the thickness of the metal plate and not the material. The thickness of the
      metal plate suitable for the evaluation of section thickness is 0.3 mm that is
      equivalent to pixel size of the flat panel detector (FPD). We conducted
      quantitative verification to establish the measurement method of the section
      thickness. The edge method is a useful technique as well as the wire and bead
      method for grasping basic characteristics of an imaging system.

PMID- 29057773
TI  - Development of Realistic Striatal Digital Brain (SDB) Phantom for 123I-FP-CIT
      SPECT and Effect on Ventricle in the Brain for Semi-quantitative Index of
      Specific Binding Ratio.
AB  - PURPOSE: This study aimed at developing the realistic striatal digital brain
      (SDB) phantom and to assess specific binding ratio (SBR) for ventricular effect
      in the 123I-FP-CIT SPECT imaging. METHODS: SDB phantom was constructed in to four
      segments (striatum, ventricle, brain parenchyma, and skull bone) using Percentile
      method and other image processing in the T2-weighted MR images. The reference
      image was converted into 128*128 matrixes to align MR images with SPECT images.
      The process image was reconstructed with projection data sets generated from
      reference images additive blurring, attenuation, scatter, and statically noise.
      The SDB phantom was evaluated to find the accuracy of calculated SBR and to find
      the effect of SBR with/without ventricular counts with the reference and process
      images. RESULTS: We developed and investigated the utility of the SDB phantom in
      the 123I-FP-CIT SPECT clinical study. The true value of SBR was just marched to
      calculate SBR from reference and process images. The SBR was underestimated 58.0%
      with ventricular counts in reference image, however, was underestimated 162% with
      ventricular counts in process images. CONCLUSION: The SDB phantom provides an
      extremely convenient tool for discovering basic properties of 123I-FP-CIT SPECT
      clinical study image. It was suggested that the SBR was susceptible to ventricle.

PMID- 29057774
TI  - Scatter Correction of Septal Penetration for 123I-IMP Cerebral Blood Flow SPECT
      Adding Radioactivity from the Outside of Field of View-Comparison between
      Simulation-based and Multi-window Scatter Corrections.
AB  - PURPOSE: The N-Isopropyl-p-[123I] Iodoamphetamine (123I-IMP) SPECT imaging
      reduces the image quality and quantitative accuracy due to scatter and septal
      penetration occurred by radioactive uptake from outside of the field of view such
      as the lungs. We evaluated the influence of scatter and septal penetration using
      phantom-simulated radioactivity from outside of the field of view, and
      subsequently compared the effect of scatter and septal penetration corrections
      between the simulation-based effective scatter source estimation (ESSE) method
      and the multi-window method (ellipse approximation method). METHODS: We used the
      phantom filled with 10 and 25 kBq/mL for the brain and lung parts corresponding
      to radioactive concentration in the clinical study. The SPECT images were
      acquired with and without lung phantom using low-energy high-resolution (LEHR)
      and cardiac high-resolution (CHR) collimators. We quantitatively evaluated a
      brain phantom by count analysis and coefficient of variation as reference data
      without lung phantom simulated the radioactivity from outside of the field of
      view, and compared between two scatter corrections by each collimator. RESULTS:
      The brain count in cerebral base with the ESSE method using LEHR collimator was
      higher than that of the ellipse approximation method. The whole brain count with
      the ellipse approximation method using CHR collimator shows 28.8% lower than the
      ESSE method, so that it suggests that the ellipse approximation method for LEHR
      collimator and the ESSE method for CHR collimator was close to reference counts.
      The coefficient of variation of the ESSE method was lower than that of the
      ellipse approximation method for both two collimators. CONCLUSIONS: It was
      possible to correct the scatter and penetration from outside the field of view
      with high accuracy, by using the ellipse approximation method with LEHR
      collimator and the ESSE method with CHR collimator.

PMID- 29057775
TI  - Influence of the Pixel Sizes of Reference Computed Tomography on Single-photon
      Emission Computed Tomography Image Reconstruction Using Conjugate-gradient
      Algorithm.
AB  - PURPOSE: The frame-of-reference using computed-tomography (CT) coordinate system
      on single-photon emission computed tomography (SPECT) reconstruction is one of
      the advanced characteristics of the xSPECT reconstruction system. The aim of this
      study was to reveal the influence of the high-resolution frame-of-reference on
      the xSPECT reconstruction. METHODS: 99mTc line-source phantom and National
      Electrical Manufacturers Association (NEMA) image quality phantom were scanned
      using the SPECT/CT system. xSPECT reconstructions were performed with the
      reference CT images in different sizes of the display field-of-view (DFOV) and
      pixel. RESULTS: The pixel sizes of the reconstructed xSPECT images were close to
      2.4 mm, which is acquired as originally projection data, even if the reference CT
      resolution was varied. The full width at half maximum (FWHM) of the line-source,
      absolute recovery coefficient, and background variability of image quality
      phantom were independent on the sizes of DFOV in the reference CT images.
      CONCLUSION: The results of this study revealed that the image quality of the
      reconstructed xSPECT images is not influenced by the resolution of frame-of
      reference on SPECT reconstruction.

PMID- 29057776
TI  - Reduction Method of Operator and Medical Staff Radiation Exposure in Balloon
      Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.
AB  - The purpose of this study is to investigate a reduction method of radiation
      exposure for operator and medical staff in balloon pulmonary angioplasty (BPA)
      for chronic thromboembolic pulmonary hypertension (CTEPH). We devised a new
      radiation protection, which is U-shaped acrylic supporting table with 0.35 mmPb
      unleaded radiation protection sheet. A human phantom was put on the bed of
      cardiac angiography system [C-arm angulation: posteroanterior (PA), L-arm
      angulation: left anterior oblique (LAO) 60 degrees ]. The ambient equivalent dose
      rate was measured under fluoroscopy with and without three radiation protections:
      U-shaped acrylic supporting table with 0.35 mmPb unleaded radiation protection
      sheet, radiation protection for the lower body, and radiation protection for the
      upper body. With the three radiation protections, the ambient equivalent dose
      rate was decreased more than 99% at the height of 100 cm above the floor at the
      operator position (PA: from 186.2 MUSv/h to 0.5 MUSv/h, LAO 60 degrees : from
      350.4 MUSv/h to 1.6 MUSv/h). Ambient equivalent dose rate at the other points are
      also decreased effectively. The devised dose reduction method can reduce operator
      and medical staff radiation exposure effectively and be set up without
      interference for BPA procedure.

PMID- 29057777
TI  - Evaluation of Accuracy for Quantitative Predictor of Hepatic Functional Reserve
      Using Planar and SPECT Images in the 99mTc-GSA Scintigraphy.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy for quantitative
      predictor of hepatic functional reserve using planar and single photon emission
      computed tomography (SPECT) images. METHODS: We acquired planar and SPECT images
      of the myocardial torso phantom and calculated LHL (uptake ratio of the liver to
      the liver plus heart). Planar images were used with and without scatter
      correction. Myocardial torso phantom was simulated radioactivity distribution of
      normal liver function and poor liver function. This study compared the LHLplanar
      (calculated by planar images) and the LHLSPECT (calculated by SPECT images) with
      the true value (calculated by radioactivity concentration in the phantom) and
      evaluated the error rate. RESULTS: Error rate of LHLSPECT was improved compared
      with the LHLplanar. The error rate of LHLplanar (with scatter correction) was
      increased in the poor liver function than in the normal liver function.
      CONCLUSIONS: The SPECT images have higher advantage to predict the liver function
      than the planar images.

PMID- 29057778
TI  - Survey of Careers and Achievements on Delegates in JSRT International Delegation
      Projects.
AB  - Japanese society of radiological technology (JSRT) categorizes three
      international delegation projects; short-term studying abroad program (STSAP),
      international academic society visit program (overseas) (IASVP), and
      international internship visit program (Stanford University) (IIVP) for driving
      globalization of JSRT. In this survey, we conducted a questionnaire evaluating
      effectiveness of the international delegations. The survey covered 50 delegates
      of STSAP, 180 delegates of IASVP, and 100 delegates of IIVP. This survey includes
      detailed histories of career, current position, academic articles, and
      presentations as a first presenter before and on, and after each program. We
      categorized into six groups (change career, promoted in a position in hospital,
      kept a current position in hospital, promoted in a position in university, kept a
      current position in university, and others) in three programs. The response rate
      is approximately 58% (191/330 delegators). In all programs, almost all the
      delegates were radiological technologists in the hospital. They had reported a
      lot of academic articles and made a lot of presentations, and promoted in the
      hospital and/or university. STSAP, IASVP and IIVP were descending order of the
      average number of the articles as a first author and presentations as a first
      presenter. They published more the academic articles in Japanese than in English
      compared to JJRT and RPT. Therefore, research achievements and human resource
      conducted by this project provide great technologists and technique, and
      education. For further JRST globalization, it is desirable that we can continue
      these international delegations and verify the effectiveness.

PMID- 29057779
TI  - Reirradiation.

PMID- 29057780
TI  - 5. DRL for Computed Tomography Examination.

PMID- 29057781
TI  - 1. A Possibility of Life Science Research Pioneered by Radiological Science and
      Technology.

PMID- 29057782
TI  - 6. Quantitative Evaluation of the Bone Scintigraphy in the Prostate Cancer.

PMID- 29057783
TI  - Development of Automation Program for Quality Control of CR System Using DR
      Phantom.

PMID- 29057784
TI  - Act against Unjustifiable Premiums and Misleading Presentations.

PMID- 29057785
TI  - Treasure Every Encounter, for It Will Never Recur.

PMID- 29057786
TI  - Errata: Do Implantable Cardioverter Defibrillators Reduce Mortality in Patients
      With Chronic Kidney Disease at All Stages? An Updated Meta-Analysis.
AB  - The errors in the following list appeared in the article titled "Do Implantable
      Cardioverter Defibrillators Reduce Mortality in Patients With Chronic Kidney
      Disease at All Stages?: An Updated Meta-Analysis" by Linghua Fu, Qiongqiong Zhou,
      Wengen Zhu, Lin Huang, Ying Ding, Yang Shen, Jinzhu Hu, and Kui Hong (Vol. 58,
      No. 3, 371-7, 2017).

PMID- 29057788
TI  - Relationship between Self-Rated Health and Lifestyle and Food Habits in Japanese
      High School Students.
AB  - Self-rated health (SRH), a subjective assessment of health status, is extensively
      used in the field of public health. It is an important and valid measure that is
      strongly related to morbidity, mortality, longevity and health status.
      Adolescence is a crucial period for the formation of health status, because
      health-risk behaviours (e.g., skipping breakfast) are often established during
      this period. In this study, we investigated the relationship of SRH with
      lifestyle and eating habits in Japanese high school students. In this study, 1296
      students aged 16-18 years from 11 high schools in Japan participated. A
      questionnaire was administered to these participants that included a question on
      SRH, five questions on demographic characteristics, six questions on lifestyle
      items (e.g., wake-up time), five questions on miscellaneous health issues (e.g.,
      anorexia), and 25 questions on food habits and attitudes towards food. We
      examined the differences between self-rated healthy and unhealthy groups using
      logistic regression analysis adjusted for gender and age. A dichotomy regression
      analysis was performed using a stepwise elimination method. Of the 1296
      respondents, 16.7% reported feeling unhealthy, 57.7% of whom were females. The
      self-rated healthy group had a higher frequency of eating breakfast (odds ratio
      (OR): 2.13; confidence interval (CI): 1.07-4.24) and liked home meals to a
      greater extent (OR: 3.12; CI: 1.27-7.65) than the self-rated unhealthy group. The
      two groups did not differ significantly in terms of other lifestyle factors or
      unidentified complaints. Our results suggest that liking home meals during
      adolescence may lead to the development of good eating habits, i.e., eating
      breakfast, and better SRH.

PMID- 29057787
TI  - Vitamin D in Pain Management.
AB  - Vitamin D is a hormone synthesized in the skin in the presence of sunlight. Like
      other hormones, vitamin D plays a role in a wide range of processes in the body.
      Here we review the possible role of vitamin D in nociceptive and inflammatory
      pain. In observational studies, low vitamin D levels have been associated with
      increased pain and higher opioid doses. Recent interventional studies have shown
      promising effects of vitamin D supplementation on cancer pain and muscular pain
      but only in patients with insufficient levels of vitamin D when starting
      intervention. Possible mechanisms for vitamin D in pain management are the anti
      inflammatory effects mediated by reduced cytokine and prostaglandin release and
      effects on T-cell responses. The recent finding of vitamin D-mediated inhibition
      of Prostaglandin E2 (PGE2) is especially interesting and exhibits a credible
      mechanistic explanation. Having reviewed current literature, we suggest that
      patients with deficient levels defined as 25-hydroxyvitamin D (25-OHD) levels <30
      nmol/L are most likely to benefit from supplementation, while individuals with 25
      OHD >50 nmol/L probably have little benefit from supplementation. Our conclusion
      is that vitamin D may constitute a safe, simple and potentially beneficial way to
      reduce pain among patients with vitamin D deficiency, but that more randomized
      and placebo-controlled studies are needed before any firm conclusions can be
      drawn.

PMID- 29057789
TI  - Overexpression of Populus trichocarpa Mitogen-Activated Protein Kinase Kinase4
      Enhances Salt Tolerance in Tobacco.
AB  - Mitogen-activated protein kinase (MAPK) is one of the factors of cascade
      reactions affecting responses to signal pathway of environmental stimuli.
      Throughout the life of plants, MAPK family members participate in signal
      transduction pathways and regulate various intracellular physiological and
      metabolic reactions. To gain insights into regulatory function of MAPK kinase
      (MAPKK) in Populus trichocarpa under salt stress, we obtained full-length cDNA of
      PtMAPKK4 and analyzed different expression levels of PtMAPKK4 gene in leaves,
      stems, and root organs. The relationship between PtMAPKK4 and salt stress was
      studied by detecting expression characteristics of mRNA under 150 mM NaCl stress
      using real-time quantitative polymerase chain reaction. The results showed that
      expression of PtMAPKK4 increased under salt (NaCl) stress in leaves but initially
      reduced and then increased in roots. Thus, salt stress failed to induce PtMAPKK4
      expression in stems. PtMAPKK4 possibly participates in regulation of plant growth
      and metabolism, thereby improving its salt tolerance. We used Saccharomyces
      cerevisiae strain INVScI to verify subcellular localization of PtMAPKK4 kinase.
      The yeast strains containing pYES2-PtMAPKK4-GFP plasmid expressed GFP fusion
      proteins under the induction of d-galactose, and the products were located in
      nucleus. These results were consistent with network prediction and confirmed
      location of PtMAPKK4 enzyme in the nucleus. We tested NaCl tolerance in
      transgenic tobacco lines overexpressing PtMAPKK4 under the control of 35S
      promoter at germination stage to detect salt tolerance function of PtMAPKK4.
      Compared withK326 (a wild-type tobacco), lines overexpressing PtMAPKK4 showed a
      certain degree of improvement in tolerance, germination, and growth. NaCl
      inhibited growth of overexpressed line and K326 at the seedling stage. However,
      statistical analysis showed longer root length, higher fresh weight, and lower
      MDA content in transgenic lines in comparison with that in K326.

PMID- 29057790
TI  - Marine Viruses: Key Players in Marine Ecosystems.
AB  - Viruses were recognized as the causative agents of fish diseases, such as
      infectious pancreatic necrosis and Oregon sockeye disease, in the early 1960s
      [1], and have since been shown to be responsible for diseases in all marine life
      from bacteria to protists, mollusks, crustaceans, fish and mammals [2].[...].

PMID- 29057792
TI  - Classification of Data from Electronic Nose Using Gradient Tree Boosting
      Algorithm.
AB  - In this paper, an approach that can fast classify the data from the electronic
      nose is presented. In this approach the gradient tree boosting algorithm is used
      to classify the gas data and the experiment results show that the proposed
      gradient tree boosting algorithm achieved high performance on this classification
      problem, outperforming other algorithms as comparison. In addition, electronic
      nose we used only requires a few seconds of data after the gas reaction begins.
      Therefore, the proposed approach can realize a fast recognition of gas, as it
      does not need to wait for the gas reaction to reach steady state.

PMID- 29057793
TI  - Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant
      Capacity in Wheat Exposed to Nano-ZnO Stress.
AB  - The release of nanoparticles into the environment is inevitable, which has raised
      global environmental concern. Melatonin is involved in various stress responses
      in plants. The present study investigated the effects of melatonin on
      photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed
      plants. It was found that melatonin improved the photosynthetic C assimilation in
      nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy
      transport efficiency, higher chlorophyll concentration and higher activities of
      Rubisco and ATPases. In addition, melatonin enhanced the activities of
      antioxidant enzymes to protect the photosynthetic electron transport system in
      wheat leaves against the oxidative burst caused by nano-ZnO stress. These results
      suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO
      stress.

PMID- 29057794
TI  - Food and Beverage Availability in Small Food Stores Located in Healthy Food
      Financing Initiative Eligible Communities.
AB  - Food deserts are a major public health concern. This study aimed to assess food
      and beverage availability in four underserved communities eligible to receive
      funding from the Healthy Food Financing Initiative (HFFI). Data analyzed are part
      of a quasi-experimental study evaluating the impact of the HFFI on the retail
      food environment in selected Illinois communities. In 2015, 127 small grocery and
      limited service stores located in the four selected communities were audited. All
      communities had a large percentage of low-income and African-American residents.
      Differences in food and beverage item availability (e.g., produce, milk, bread,
      snack foods) were examined by store type and community location. Food stores had,
      on average, 1.8 fresh fruit and 2.9 fresh vegetable options. About 12% of stores
      sold low-fat milk while 86% sold whole milk. Only 12% of stores offered 100%
      whole wheat bread compared to 84% of stores offering white bread. Almost all
      (97%) stores offered soda and/or fruit juice. In summary, we found limited
      availability of healthier food and beverage items in the communities identified
      for HFFI support. Follow up findings will address how the introduction of new
      HFFI-supported supermarkets will affect food and beverage availability in these
      communities over time.

PMID- 29057791
TI  - Emerging Therapeutics to Overcome Chemoresistance in Epithelial Ovarian Cancer: A
      Mini-Review.
AB  - Ovarian cancer is the fifth leading cause of cancer death among women and the
      most lethal gynecologic malignancy. One of the leading causes of death in high
      grade serous ovarian cancer (HGSOC) is chemoresistant disease, which may present
      as intrinsic or acquired resistance to therapies. Here we discuss some of the
      known molecular mechanisms of chemoresistance that have been exhaustively
      investigated in chemoresistant ovarian cancer, including drug efflux pump
      multidrug resistance protein 1 (MDR1), the epithelial-mesenchymal transition, DNA
      damage and repair capacity. We also discuss novel therapeutics that may address
      some of the challenges in bringing approaches that target chemoresistant
      processes from bench to bedside. Some of these new therapies include novel drug
      delivery systems, targets that may halt adaptive changes in the tumor,
      exploitation of tumor mutations that leave cancer cells vulnerable to
      irreversible damage, and novel drugs that target ribosomal biogenesis, a process
      that may be uniquely different in cancer versus non-cancerous cells. Each of
      these approaches, or a combination of them, may provide a greater number of
      positive outcomes for a broader population of HGSOC patients.

PMID- 29057796
TI  - Six Years (2011-2016) of Mandatory Nationwide Bovine Viral Diarrhea Control in
      Germany-A Success Story.
AB  - Bovine viral diarrhea (BVD) is one of the most important infectious diseases in
      cattle, causing major economic losses worldwide. Therefore, control programs have
      been implemented in several countries. In Germany, an obligatory nationwide
      eradication program has been in force since 2011. Its centerpiece is the
      detection of animals persistently infected (PI) with BVD virus, primarily based
      on the testing of ear tissue samples of all newborn calves for viral genome or
      antigen, and their removal from the cattle population. More than 48,000 PI
      animals have so far been detected and removed. Between the onset of the program
      and the end of 2016, the prevalence of these animals among all newborn calves
      decreased considerably, from 0.5% to less than 0.03%. The number of cattle
      holdings with PI animals likewise decreased from 3.44% in 2011 to only 0.16% in
      2016. Since a large number of naive, fully susceptible animals are now confronted
      with BVD virus, which is still present in the German cattle population, the
      challenge of the coming years will be the identification of remaining PI animals
      as quickly and efficiently as possible, and the efficient protection of BVD-free
      farms from reinfection.

PMID- 29057797
TI  - Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical
      Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine
      Pancreatic beta-Cells.
AB  - We previously identified a novel apoptosis-inducing humoral factor in the
      conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel
      post-translationally-modified secreted-form of eukaryotic translation initiation
      factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We
      confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP
      levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by
      neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to
      investigate the mechanism of cell injury of cardiac myocytes and pancreatic beta
      cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM
      model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac
      myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis
      in pancreatic beta-cells. Plasma ORAIP levels in DM rats during diabetic phase
      were about 18 times elevated as compared with non-diabetic phase. High glucose
      induced massive apoptosis in cardiac myocytes (66.2 +/- 2.2%), which was 78%
      suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant
      ORAIP clearly induced apoptosis in pancreatic beta-cells in vitro. These findings
      strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced
      myocardial injury and pancreatic beta-cell injury in DM. ORAIP will be a
      biomarker and a critical therapeutic target for cardiac injury and progression of
      DM itself.

PMID- 29057795
TI  - The Effect of Piceatannol from Passion Fruit (Passiflora edulis) Seeds on
      Metabolic Health in Humans.
AB  - Animal studies have shown the beneficial effects of piceatannol on metabolic
      health; however, there is a lack of human studies designed to examine these
      effects. The objective of this study was to investigate the effects of
      piceatannol on metabolic health in humans. This randomized, placebo-controlled
      study was conducted on 39 subjects, including 10 overweight men and 9 overweight
      women (BMI >= 25), as well as 10 non-overweight men and 10 non-overweight women
      (BMI < 25). Subjects received piceatannol (20 mg/day) or placebo capsules for
      eight weeks in a random order. The primary outcome was the effect of piceatannol
      on glucose-metabolism, including insulin sensitivity. The secondary outcomes were
      the effects on other parameters, including blood pressure (BP), heart rate (HR),
      endothelial function, lipids, inflammation, oxidative stress, mood status, and
      Sirt1 and phospho-AMP-activated kinase (p-AMPK) expression in isolated peripheral
      blood mononuclear cells (PBMNCs). Supplementation with piceatannol in overweight
      men reduced serum insulin levels, HOMA-IR, BP and HR. Other groups, including non
      overweight men, as well as overweight and non-overweight women, showed no
      beneficial effects on insulin sensitivity, BP and HR. Furthermore, piceatannol is
      not associated with other data, including body weight (BW), body composition,
      endothelial function, lipids, inflammation, oxidative stress, mood status, and
      Sirt1/p-AMPK expression in PBMNCs. In conclusion, supplementation with
      piceatannol can improve metabolic health, including insulin sensitivity, BP and
      HR, in overweight men.

PMID- 29057798
TI  - Production, Characterisation and Testing of an Ovine Antitoxin against Ricin;
      Efficacy, Potency and Mechanisms of Action.
AB  - Ricin is a type II ribosome-inactivating toxin that catalytically inactivates
      ribosomes ultimately leading to cell death. The toxicity of ricin along with the
      prevalence of castor beans (its natural source) has led to its increased
      notoriety and incidences of nefarious use. Despite these concerns, there are no
      licensed therapies available for treating ricin intoxication. Here, we describe
      the development of a F(ab')2 polyclonal ovine antitoxin against ricin and
      demonstrate the efficacy of a single, post-exposure, administration in an in vivo
      murine model of intoxication against aerosolised ricin. We found that a single
      dose of antitoxin afforded a wide window of opportunity for effective treatment
      with 100% protection observed in mice challenged with aerosolised ricin when
      given 24 h after exposure to the toxin and 75% protection when given at 30 h.
      Treated mice had reduced weight loss and clinical signs of intoxication compared
      to the untreated control group. Finally, using imaging flow cytometry, it was
      found that both cellular uptake and intracellular trafficking of ricin toxin to
      the Golgi apparatus was reduced in the presence of the antitoxin suggesting both
      actions can contribute to the therapeutic mechanism of a polyclonal antitoxin.
      Collectively, the research highlights the significant potential of the ovine
      F(ab')2 antitoxin as a treatment for ricin intoxication.

PMID- 29057799
TI  - A Monoclonal-Monoclonal Antibody Based Capture ELISA for Abrin.
AB  - Abrin, one of the most highly potent toxins in the world, is derived from the
      plant, Abrus precatorius. Because of its high toxicity, it poses potential
      bioterror risks. Therefore, a need exists for new reagents and technologies that
      would be able to rapidly detect abrin contamination as well as lead to new
      therapeutics. We report here a group of abrin-specific monoclonal antibodies
      (mAbs) that recognize abrin A-chain, intact A-B chain toxin, and agglutinin by
      Western blot. Additionally, these mAbs were evaluated for their ability to serve
      as capture antibodies for a sandwich (capture) ELISA. All possible capture
      detector pairs were evaluated and the best antibody pair identified and optimized
      for a capture ELISA. The capture ELISA based on this capture-detector mAb pair
      had a limit of detection (L.O.D) of ~1 ng/mL measured using three independent
      experiments. The assay did not reveal any false positives with extracts
      containing other potential ribosome-inactivating proteins (RIPs). Thus, this new
      capture ELISA uses mAbs for both capture and detection; has no cross-reactivity
      against other plant RIPs; and has a sensitivity comparable to other reported
      capture ELISAs using polyclonal antibodies as either capture or detector.

PMID- 29057800
TI  - Novel Bioactive Paulomycin Derivatives Produced by Streptomyces albus J1074.
AB  - Four novel paulomycin derivatives have been isolated from S. albus J1074 grown in
      MFE culture medium. These compounds are structural analogs of antibiotics
      273a2alpha and 273a2beta containing a thiazole moiety, probably originated
      through an intramolecular Michael addition. The novel, thiazole, moiety
      containing paulomycins show a lower antibiotic activity than paulomycins A and B
      against Gram-positive bacteria. However, two of them show an improved activity
      against Gram-negative bacteria. In addition, the four novel compounds are more
      stable in culture than paulomycins A and B. Thus, the presence of an N-acetyl-l
      cysteine moiety linked to the carbon atom of the paulic acid isothiocyanate
      moiety, via a thioester bond, and the subsequent intramolecular cyclization of
      the paulic acid to generate a thiazole heterocycle confer to paulomycins a higher
      structural stability that otherwise will conduce to paulomycin degradation and
      into inactive paulomenols.

PMID- 29057801
TI  - Revealing the Effects of Nanoscale Membrane Curvature on Lipid Mobility.
AB  - Recent advances in nanoengineering and super-resolution microscopy have enabled
      new capabilities for creating and observing membrane curvature. However, the
      effects of curvature on single-lipid diffusion have yet to be revealed. The
      simulations presented here describe the capabilities of varying experimental
      methods for revealing the effects of nanoscale curvature on single-molecule
      mobility. Traditionally, lipid mobility is revealed through fluorescence recovery
      after photobleaching (FRAP), fluorescence correlation spectroscopy (FCS), and
      single particle tracking (SPT). However, these techniques vary greatly in their
      ability to detect the effects of nanoscale curvature on lipid behavior.
      Traditionally, FRAP and FCS depend on diffraction-limited illumination and
      detection. A simulation of FRAP shows minimal effects on lipids diffusion due to
      a 50 nm radius membrane bud. Throughout the stages of the budding process, FRAP
      detected minimal changes in lipid recovery time due to the curvature versus flat
      membrane. Simulated FCS demonstrated small effects due to a 50 nm radius membrane
      bud that was more apparent with curvature-dependent lipid mobility changes.
      However, SPT achieves a sub-diffraction-limited resolution of membrane budding
      and lipid mobility through the identification of the single-lipid positions with
      <=15 nm spatial and <=20 ms temporal resolution. By mapping the single-lipid step
      lengths to locations on the membrane, the effects of membrane topography and
      curvature could be correlated to the effective membrane viscosity. Single
      fluorophore localization techniques, such SPT, can detect membrane curvature and
      its effects on lipid behavior. These simulations and discussion provide a
      guideline for optimizing the experimental procedures in revealing the effects of
      curvature on lipid mobility and effective local membrane viscosity.

PMID- 29057802
TI  - Patient Aggression and the Wellbeing of Nurses: A Cross-Sectional Survey Study in
      Psychiatric and Non-Psychiatric Settings.
AB  - Wellbeing of nurses is associated with patient aggression. Little is known about
      the differences in these associations between nurses working in different
      specialties. We aimed to estimate and compare the prevalence of patient
      aggression and the associations between patient aggression and the wellbeing of
      nurses in psychiatric and non-psychiatric specialties (medical and surgical, and
      emergency medicine). A sample of 5288 nurses (923 psychiatric nurses, 4070
      medical and surgical nurses, 295 emergency nurses) participated in the study.
      Subjective measures were used to assess both the occurrence of patient aggression
      and the wellbeing of nurses (self-rated health, sleep disturbances, psychological
      distress and perceived work ability). Binary logistic regression with interaction
      terms was used to compare the associations between patient aggression and the
      wellbeing of nurses. Psychiatric nurses reported all types of patient aggression
      more frequently than medical and surgical nurses, whereas nurses working in
      emergency settings reported physical violence and verbal aggression more
      frequently than psychiatric nurses. Psychiatric nurses reported poor self-rated
      health and reduced work ability more frequently than both of the non-psychiatric
      nursing groups, whereas medical and surgical nurses reported psychological
      distress and sleep disturbances more often. Psychiatric nurses who had
      experienced at least one type of patient aggression or mental abuse in the
      previous year, were less likely to suffer from psychological distress and sleep
      disturbances compared to medical and surgical nurses. Psychiatric nurses who had
      experienced physical assaults and armed threats were less likely to suffer from
      sleep disturbances compared to nurses working in emergency settings. Compared to
      medical and surgical nurses, psychiatric nurses face patient aggression more
      often, but certain types of aggression are more common in emergency settings.
      Psychiatric nurses have worse subjective health and work ability than both of the
      non-psychiatric nursing groups, while their psychiatric wellbeing is better and
      they have less sleep problems compared to medical and surgical nurses.
      Psychiatric nurses maintain better psychiatric wellbeing and experience fewer
      sleep problems than non-psychiatric nurses after events of exposure to patient
      aggression. This suggest that more attention should be given to non-psychiatric
      settings for maintaining the wellbeing of nurses after exposure to patient
      aggression.

PMID- 29057803
TI  - Identification and Characterization of an Isoform Antifreeze Protein from the
      Antarctic Marine Diatom, Chaetoceros neogracile and Suggestion of the Core
      Region.
AB  - Antifreeze proteins (AFPs) protecting the cells against freezing are produced in
      response to extremely low temperatures in diverse psychrophilic organisms, and
      they are encoded by multiple gene families. The AFP of Antarctic marine diatom
      Chaetoceros neogracile is reported in our previous research, but like other
      microalgae, was considered to probably have additional genes coding AFPs. In this
      paper, we reported the cloning and characterization of additional AFP gene from
      C. neogracile (Cn-isoAFP). Cn-isoAFP protein is 74.6% identical to the previously
      reported Cn-AFP. The promoter sequence of Cn-isoAFP contains environmental stress
      responsive elements for cold, thermal, and high light conditions. Cn-isoAFP
      transcription levels increased dramatically when cells were exposed to freezing (
      20  degrees C), thermal (10  degrees C), or high light (600 MUmol photon m-2 s-1)
      stresses. The thermal hysteresis (TH) activity of recombinant Cn-isoAFP was 0.8 
      degrees C at a protein concentration of 5 mg/mL. Results from homology modeling
      and TH activity analysis of site-directed mutant proteins elucidated AFP
      mechanism to be a result of flatness of B-face maintained via hydrophobic
      interactions.

PMID- 29057805
TI  - Performance Analysis for Joint Target Parameter Estimation in UMTS-Based Passive
      Multistatic Radar with Antenna Arrays Using Modified Cramer-Rao Lower Bounds.
AB  - In this study, the modified Cramer-Rao lower bounds (MCRLBs) on the joint
      estimation of target position and velocity is investigated for a universal mobile
      telecommunication system (UMTS)-based passive multistatic radar system with
      antenna arrays. First, we analyze the log-likelihood redfunction of the received
      signal for a complex Gaussian extended target. Then, due to the non-deterministic
      transmitted data symbols, the analytically closed-form expressions of the MCRLBs
      on the Cartesian coordinates of target position and velocity are derived for a
      multistatic radar system with N t UMTS-based transmit station of L t antenna
      elements and N r receive stations of L r antenna elements. With the aid of
      numerical simulations, it is shown that increasing the number of receiving
      elements in each receive station can reduce the estimation errors. In addition,
      it is demonstrated that the MCRLB is not only a function of signal-to-noise ratio
      (SNR), the number of receiving antenna elements and the properties of the
      transmitted UMTS signals, but also a function of the relative geometric
      configuration between the target and the multistatic radar system.The analytical
      expressions for MCRLB will open up a new dimension for passive multistatic radar
      system by aiding the optimal placement of receive stations to improve the target
      parameter estimation performance.

PMID- 29057804
TI  - Nrf2-Inducers Counteract Neurodegeneration in Frataxin-Silenced Motor Neurons:
      Disclosing New Therapeutic Targets for Friedreich's Ataxia.
AB  - Oxidative stress is actively involved in Friedreich's Ataxia (FA), thus
      pharmacological targeting of the antioxidant machinery may have therapeutic
      value. Here, we analyzed the relevance of the antioxidant phase II response
      mediated by the transcription factor Nrf2 on frataxin-deficient cultured motor
      neurons and on fibroblasts of patients. The in vitro treatment of the potent Nrf2
      activator sulforaphane increased Nrf2 protein levels and led to the upregulation
      of phase II antioxidant enzymes. The neuroprotective effects were accompanied by
      an increase in neurites' number and extension. Sulforaphane (SFN) is a natural
      compound of many diets and is now being used in clinical trials for other
      pathologies. Our results provide morphological and biochemical evidence to
      endorse a neuroprotective strategy that may have therapeutic relevance for FA.
      The findings of this work reinforce the crucial importance of Nrf2 in FA and
      provide a rationale for using Nrf2-inducers as pharmacological agents.

PMID- 29057806
TI  - Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia
      via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways.
AB  - Lasting activations of toll-like receptors (TLRs), MAPK and NF-kappaB pathways
      can support influenza A virus (IAV) infection and promote pneumonia. In this
      study, we have investigated the effect and mechanism of action of emodin on IAV
      infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA
      and plaque inhibition assays. The results showed that emodin could significantly
      inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of
      TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK
      MAPK and nuclear translocation of NF-kappaB p65. Emodin also activated the Nrf2
      pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and
      upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection.
      Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin
      on IAV-induced activations of TLR4, p38/JNK, and NF-kappaB pathways and on IAV
      induced production of IL-1beta, IL-6 and expression of IAV M2 protein. Emodin
      also dramatically increased the survival rate of mice, reduced lung edema,
      pulmonary viral titer and inflammatory cytokines, and improved lung
      histopathological changes. In conclusion, emodin can inhibit IAV replication and
      influenza viral pneumonia, at least in part, by activating Nrf2 signaling and
      inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-kappaB
      pathways.

PMID- 29057807
TI  - Wound-Healing Peptides for Treatment of Chronic Diabetic Foot Ulcers and Other
      Infected Skin Injuries.
AB  - As the incidence of diabetes continues to increase in the western world, the
      prevalence of chronic wounds related to this condition continues to be a major
      focus of wound care research. Additionally, over 50% of chronic wounds exhibit
      signs and symptoms that are consistent with localized bacterial biofilms
      underlying severe infections that contribute to tissue destruction, delayed wound
      healing and other serious complications. Most current biomedical approaches for
      advanced wound care aim at providing antimicrobial protection to the open wound
      together with a matrix scaffold (often collagen-based) to boost reestablishment
      of the skin tissue. Therefore, the present review is focused on the efforts that
      have been made over the past years to find peptides possessing wound-healing
      properties, towards the development of new and effective wound care treatments
      for diabetic foot ulcers and other skin and soft tissue infections.

PMID- 29057808
TI  - Zanthoxylum bungeanum Maxim. (Rutaceae): A Systematic Review of Its Traditional
      Uses, Botany, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicology.
AB  - Zanthoxylum bungeanum Maxim. (Rutaceae) is a popular food additive and
      traditional Chinese herbal medicine commonly named HuaJiao in China. This plant
      is widely distributed in Asian countries. The aim of this paper is to provide a
      systematic review on the traditional usages, botany, phytochemistry,
      pharmacology, pharmacokinetics, and toxicology of this plant. Furthermore, the
      possible development and perspectives for future research on this plant are also
      discussed. To date, over 140 compounds have been isolated and identified from Z.
      bungeanum, including alkaloids, terpenoids, flavonoids, and free fatty acids. The
      extracts and compounds have been shown to possess wide-ranging biological
      activity, such as anti-inflammatory and analgesic effects, antioxidant and anti
      tumor effects, antibacterial and antifungal effects, as well as regulatory
      effects on the gastrointestinal system and nervous system, and other effects. As
      a traditional herbal medicine, Z. bungeanum has been widely used to treat many
      diseases, especially digestive disorders, toothache, stomach ache, and diarrhea.
      Many traditional usages of this plant have been validated by present
      investigations. However, further research elucidating the structure-function
      relationship among chemical compounds, understanding the mechanism of unique
      sensation, as well as exploring new clinical effects and establishing criteria
      for quality control for Z. bungeanum should be further studied.

PMID- 29057809
TI  - Hepatoprotective Effects of Kaempferol-3-O-alpha-l-Arabinopyranosyl-7-O-alpha-l
      Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure
      in Mice.
AB  - Fulminant hepatic failure (FHF), associated with high mortality, is characterized
      by extensive death of hepatocytes and hepatic dysfunction. There is no effective
      treatment for FHF. Several studies have indicated that flavonoids can protect the
      liver from different factor-induced injury. Previously, we found that the
      extracts of Elaeagnus mollis leaves had favorable protective effects on acute
      liver injury. However, the role and mechanisms behind that was elusive. This
      study examined the hepatoprotective mechanisms of kaempferol-3-O-alpha-l
      arabinopyranosyl-7-O-alpha-l-rhamnopyra-noside (KAR), a major flavonol glycoside
      of E. mollis, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced
      hepatic failure. KAR reduces the mouse mortality, protects the normal liver
      structure, inhibits the serum aspartate aminotransferase (AST) and alamine
      aminotransferase (ALT) activity and decreases the production of malondialdehyde
      (MDA) and reactive oxygen species (ROS) and inflammatory cytokines, TNF-alpha, IL
      6, and IL-1beta. Furthermore, KAR inhibits the apoptosis of hepatocytes and
      reduces the expression of TLR4 and NF-kappaB signaling pathway-related proteins
      induced by GalN/LPS treatment. These findings suggest that the anti-oxidative,
      anti-inflammatory, and anti-apoptotic effects of KAR on GalN/LPS-induced acute
      liver injury were performed through down-regulating the activity of the TLR4 and
      NF-kappaB signaling pathways.

PMID- 29057810
TI  - Synthesis, Characterization, and Biological Evaluations of 1,3,5-Triazine
      Derivatives of Metformin Cyclization with Berberine and Magnolol in the Presence
      of Sodium Methylate.
AB  - The novel target products were synthesized in the formation of a triazine ring
      from berberine, magnolol, and metformin catalyzed by sodium methylate. The
      structures of products 1-3 were firstly confirmed by extensive spectroscopic
      analyses and single-crystal X-ray diffraction. The crystal structures of the
      target product 2 and the intermediate product 7b were reported for the first
      time. All target products were evaluated for their anti-inflammatory and
      antidiabetic activities against INS-1 and RAW264.1 cells in vitro and all
      products showed excellent anti-inflammatory effects and anti-insulin resistance
      effects. Our studies indicated that new compounds 1-3 were found to be active
      against inflammation and insulin resistance.

PMID- 29057811
TI  - Determination of Odour Interactions of Three-Component Gas Mixtures Using an
      Electronic Nose.
AB  - The paper presents an application of an electronic nose prototype comprised of
      six TGS-type sensors and one PID-type sensor to identify odour interaction
      phenomena in odorous three-component mixtures. The investigation encompassed
      eight odorous mixtures-toluene-acetone-triethylamine and formaldehyde-butyric
      acid-pinene-characterized by different odour intensity and hedonic tone. A
      principal component regression (PCR) calibration model was used for evaluation of
      predicted odour intensity and hedonic tone. Correctness of identification of
      odour interactions in the odorous three-component mixtures was determined based
      on the results obtained with the electronic nose. The results indicated a level
      of 75-80% for odour intensity and 57-73% for hedonic tone. The average root mean
      square error of prediction amounted to 0.03-0.06 for odour intensity
      determination and 0.07-0.34 for hedonic tone evaluation of the odorous three
      component mixtures.

PMID- 29057812
TI  - Sensor-Data Fusion for Multi-Person Indoor Location Estimation.
AB  - We consider the problem of estimating the location of people as they move and
      work in indoor environments. More specifically, we focus on the scenario where
      one of the persons of interest is unable or unwilling to carry a smartphone, or
      any other "wearable" device, which frequently arises in caregiver/cared-for
      situations. We consider the case of indoor spaces populated with anonymous binary
      sensors (Passive Infrared motion sensors) and eponymous wearable sensors
      (smartphones interacting with Estimote beacons), and we propose a solution to the
      resulting sensor-fusion problem. Using a data set with sensor readings collected
      from one-person and two-person sessions engaged in a variety of activities of
      daily living, we investigate the relative merits of relying solely on anonymous
      sensors, solely on eponymous sensors, or on their combination. We examine how the
      lack of synchronization across different sensing sources impacts the quality of
      location estimates, and discuss how it could be mitigated without resorting to
      device-level mechanisms. Finally, we examine the trade-off between the sensors'
      coverage of the monitored space and the quality of the location estimates.

PMID- 29057813
TI  - Composition and Statistical Analysis of Biophenols in Apulian Italian EVOOs.
AB  - Extra-virgin olive oil (EVOO) is among the basic constituents of the
      Mediterranean diet. Its nutraceutical properties are due mainly, but not only, to
      a plethora of molecules with antioxidant activity known as biophenols. In this
      article, several biophenols were measured in EVOOs from South Apulia, Italy.
      Hydroxytyrosol, tyrosol and their conjugated structures to elenolic acid in
      different forms were identified and quantified by high performance liquid
      chromatography (HPLC) together with lignans, luteolin and alpha-tocopherol. The
      concentration of the analyzed metabolites was quite high in all the cultivars
      studied, but it was still possible to discriminate them through multivariate
      statistical analysis (MVA). Furthermore, principal component analysis (PCA) and
      orthogonal partial least-squares discriminant analysis (OPLS-DA) were also
      exploited for determining variances among samples depending on the interval time
      between harvesting and milling, on the age of the olive trees, and on the area
      where the olive trees were grown.

PMID- 29057814
TI  - A New Noncanonical Anionic Peptide That Translocates a Cellular Blood-Brain
      Barrier Model.
AB  - The capacity to transport therapeutic molecules across the blood-brain barrier
      (BBB) represents a breakthrough in the development of tools for the treatment of
      many central nervous system (CNS)-associated diseases. The BBB, while being
      protective against infectious agents, hinders the brain uptake of many drugs.
      Hence, finding safe shuttles able to overcome the BBB is of utmost importance.
      Herein, we identify a new BBB-translocating peptide with unique properties. For
      years it was thought that cationic sequences were mandatory for a cell
      penetrating peptide (CPP) to achieve cellular internalization. Despite being
      anionic at physiological pH, PepNeg (sequence (SGTQEEY) is an efficient BBB
      translocator that is able to carry a large cargo (27 kDa), while maintaining BBB
      integrity. In addition, PepNeg is able to use two distinct methods of
      translocation, energy-dependent and -independent, suggesting that direct
      penetration might occur when low concentrations of peptide are presented to
      cells. The discovery of this new anionic trans-BBB peptide allows the development
      of new delivery systems to the CNS and contributes to the need to rethink the
      role of electrostatic attraction in BBB-translocation.

PMID- 29057815
TI  - Further Insights into the Ciliary Gene and Protein KIZ and Its Murine Ortholog
      PLK1S1 Mutated in Rod-Cone Dystrophy.
AB  - We identified herein additional patients with rod-cone dystrophy (RCD) displaying
      mutations in KIZ, encoding the ciliary centrosomal protein kizuna and performed
      functional characterization of the respective protein in human fibroblasts and of
      its mouse ortholog PLK1S1 in the retina. Mutation screening was done by targeted
      next generation sequencing and subsequent Sanger sequencing validation. KIZ mRNA
      levels were assessed on blood and serum-deprived human fibroblasts from a control
      individual and a patient, compound heterozygous for the c.52G>T (p.Glu18*) and
      c.119_122del (p.Lys40Ilefs*14) mutations in KIZ. KIZ localization, documentation
      of cilium length and immunoblotting were performed in these two fibroblast cell
      lines. In addition, PLK1S1 immunolocalization was conducted in mouse retinal
      cryosections and isolated rod photoreceptors. Analyses of additional RCD patients
      enabled the identification of two homozygous mutations in KIZ, the known c.226C>T
      (p.Arg76*) mutation and a novel variant, the c.3G>A (p.Met1?) mutation. Albeit
      the expression levels of KIZ were three-times lower in the patient than controls
      in whole blood cells, further analyses in control- and mutant KIZ patient-derived
      fibroblasts unexpectedly revealed no significant difference between the two
      genotypes. Furthermore, the averaged monocilia length in the two fibroblast cell
      lines was similar, consistent with the preserved immunolocalization of KIZ at the
      basal body of the primary cilia. Analyses in mouse retina and isolated rod
      photoreceptors showed PLK1S1 localization at the base of the photoreceptor
      connecting cilium. In conclusion, two additional patients with mutations in KIZ
      were identified, further supporting that defects in KIZ/PLK1S1, detected at the
      basal body of the primary cilia in fibroblasts, and the photoreceptor connecting
      cilium in mouse, respectively, are involved in RCD. However, albeit the mutations
      were predicted to lead to nonsense mediated mRNA decay, we could not detect
      changes upon expression levels, protein localization or cilia length in KIZ
      mutated fibroblast cells. Together, our findings unveil the limitations of
      fibroblasts as a cellular model for RCD and call for other models such as induced
      pluripotent stem cells to shed light on retinal pathogenic mechanisms of KIZ
      mutations.

PMID- 29057816
TI  - Encapsulation-Stabilized, Europium Containing Nanoparticle as a Probe for Time
      Resolved luminescence Detection of Cardiac Troponin I.
AB  - The use of a robust optical signaling probe with a high signal-to-noise ratio is
      important in the development of immunoassays. Lanthanide chelates are a promising
      material for this purpose, which provide time-resolved luminescence (TRL) due to
      their large Stokes shift and long luminescence lifetime. From this, they have
      attracted considerable interest in the in vitro diagnostics field. However, the
      direct use of lanthanide chelates is limited because their luminescent signal can
      be easily affected by various quenchers. To overcome this drawback, strategies
      that rely on the entrapment of lanthanide chelates inside nanoparticles, thereby
      enabling the protection of the lanthanide chelate from water, have been reported.
      However, the poor stability of the lanthanide-entrapped nanoparticles results in
      a significant fluctuation in TRL signal intensity, and this still remains a
      challenging issue. To address this, we have developed a Lanthanide chelate
      Encapsulated Silica Nano Particle (LESNP) as a new immunosensing probe. In this
      approach, the lanthanide chelate is covalently crosslinked within the silane
      monomer during the silica nanoparticle formation. The resulting LESNP is
      physically stable and retains TRL properties of the parent lanthanide chelate.
      Using the probe, a highly sensitive, sandwich-based TRL immunoassay for the
      cardiac troponin I was conducted, exhibiting a limit of detection of 48 pg/mL. On
      the basis of the features of the LESNP such as TRL signaling capability,
      stability, and the ease of biofunctionalization, we expect that the LESNP can be
      widely applied in the development of TRL-based immunosensing.

PMID- 29057817
TI  - Unresolved Issues for Utilization of Atypical Antipsychotics in Schizophrenia:
      Antipsychotic Polypharmacy and Metabolic Syndrome.
AB  - Atypical antipsychotics (AAP) are the prevailing form of schizophrenia treatment
      today due to their low side effects and superior efficacy. Nevertheless, some
      issues still need to be addressed. First, there are still a large number of
      patients with treatment-resistant schizophrenia (TRS), which has led to a growing
      trend to resort to AAP polypharmacy with few side effects. Most clinical
      treatment guidelines recommend clozapine monotherapy in TRS, but around one third
      of schizophrenic patients fail to respond to clozapine. For these patients, with
      clozapine-resistant schizophrenia AAP polypharmacy is a common strategy with a
      continually growing evidence base. Second, AAP generally have great risks for
      developing metabolic syndrome, such as weight gain, abnormality in glucose, and
      lipid metabolism. These metabolic side effects have become huge stumbling blocks
      in today's schizophrenia treatment that aims to improve patients' quality of life
      as well as symptoms. The exact reasons why this particular syndrome occurs in
      patients treated with AAP is as yet unclear though factors such as interaction of
      AAP with neurotransmitter receptors, genetic pholymorphisms, type of AAPs, length
      of AAP use, and life style of schizophrenic patients that may contribute to its
      development. The present article aimed to review the evidence underlying these
      key issues and provide the most reasonable interpretations to expand the overall
      scope of antipsychotics usage.

PMID- 29057818
TI  - Chronic High Dose Zinc Supplementation Induces Visceral Adipose Tissue
      Hypertrophy without Altering Body Weight in Mice.
AB  - The trace element zinc plays an important role in human life. Zinc deficiency
      impairs growth, reproduction, metabolism and immunity in both human and animals.
      Thus, zinc supplementation is recommended in daily life. However, the effect of
      long-term chronic zinc supplementation on adipose homeostasis has not been well
      elucidated. In the current study, mice were supplemented with zinc sulfate in the
      drinking water for 20 weeks. The results suggested that chronic zinc
      supplementation impaired systemic glucose clearance after exogenous insulin or
      glucose challenges, as compared to the control mice. Further study revealed that
      chronic zinc supplementation made no difference to body weight, but increased
      visceral adipose tissue weight and adipocyte size. In addition, gene expression
      of leptin and IL6 in the visceral adipose tissue of zinc-supplemented mice were
      higher than those of control mice. Moreover, serum level of leptin of the zinc
      supplemented mice was twice as high as that of the control mice. Besides,
      phosphorylation level of AKT T308 was attenuated in the perirenal adipose tissue
      of zinc-supplemented mice. In comparison, the expression of macrophage marker
      genes and lipogenic genes were not affected by chronic zinc supplementation, but
      the protein levels of FAS and SCD1 decreased or tended to decrease in the
      perirenal adipose tissue of zinc-supplemented mice, as compared to the control
      mice. Our findings suggest that chronic high dose zinc supplementation induces
      visceral adipose tissue hypertrophy and impairs AKT signaling in perirenal
      adipose tissue.

PMID- 29057819
TI  - A National Dietary Assessment Reference Database (NDARD) for the Dutch
      Population: Rationale behind the Design.
AB  - The development of reliable Food Frequency Questionnaires (FFQs) requires
      detailed information about the level and variation of dietary intake of the
      target population. However, these data are often limited. To facilitate the
      development of new high quality FFQs and validation of existing FFQs, we
      developed a comprehensive National Dietary Assessment Reference Database (NDARD)
      detailing information about the level and variation in dietary intake of people
      20-70 years old in the general Dutch population. This paper describes the methods
      and characteristics of the population included in the NDARD database. A total of
      1063 men and 985 women agreed to participate in this study. Dietary intake data
      were collected using different FFQs, web-based and telephone-based 24-h recalls,
      as well as blood and urine-based biomarkers. The baseline FFQ was completed by
      1647 participants with a mean age of 51 +/- 12 years, BMI of 26 +/- 4 kg/m2, and
      energy intake of 2051 +/- 605 kcal/day. The percentage of total energy intake
      from proteins, carbohydrates, and fats were 15 +/- 2, 43 +/- 6, and 36 +/- 5 En%,
      respectively. A total of 1113 participants completed telephone-based recalls and
      1783 participants completed web-based recalls. This database will enable
      researchers to validate existing national FFQs and to develop new high quality
      dietary assessment methods.

PMID- 29057821
TI  - The Dynamic Response and Vibration of Functionally Graded Carbon Nanotube
      Reinforced Composite (FG-CNTRC) Truncated Conical Shells Resting on Elastic
      Foundations.
AB  - Based on the classical shell theory, the linear dynamic response of functionally
      graded carbon nanotube-reinforced composite (FG-CNTRC) truncated conical shells
      resting on elastic foundations subjected to dynamic loads is presented. The
      truncated conical shells are reinforced by single-walled carbon nanotubes
      (SWCNTs) that vary according to the linear functions of the shell thickness. The
      motion equations are solved by the Galerkin method and the fourth-order Runge
      Kutta method. In numerical results, the influences of geometrical parameters,
      elastic foundations, natural frequency parameters, and nanotube volume fraction
      of FG-CNTRC truncated conical shells are investigated. The proposed results are
      validated by comparing them with those of other authors.

PMID- 29057820
TI  - Oil Body-Bound Oleosin-rhFGF-10: A Novel Drug Delivery System that Improves Skin
      Penetration to Accelerate Wound Healing and Hair Growth in Mice.
AB  - Recombinant human fibroblast growth factor 10 (rhFGF-10) is frequently used to
      treat patients with skin injuries. It can also promote hair growth. However, the
      effective application of rhFGF-10 is limited because of its poor stability and
      transdermal absorption. In this study, polymerase chain reaction (PCR) and
      Southern blotting were used to identify transgenic safflowers carrying a gene
      encoding an oleosin-rhFGF-10 fusion protein. The size and structural integrity of
      oleosin-rhFGF-10 in oil bodies extracted from transgenic safflower seeds was
      characterized by polyacrylamide gel electrophoresis and western blotting. Oil
      body extracts containing oleosin-rhFGF-10 were topically applied to mouse skin.
      The absorption of oleosin-rhFGF-10 was studied by immunohistochemistry. Its
      efficiency in promoting wound healing and hair regeneration were evaluated in
      full thickness wounds and hair growth assays. We identified a safflower line that
      carried the transgene and expressed a 45 kDa oleosin-rhFGF-10 protein. Oil body
      bound oleosin-rhFGF-10 was absorbed by the skin with higher efficiency and speed
      compared with prokaryotically-expressed rhFGF-10. Oleosin-rhFGF-10 also enhanced
      wound closure and promoted hair growth better than rhFGF-10. The application of
      oleosin-rhFGF-10 in oil bodies promoted its delivery through the skin, providing
      a basis for improved therapeutic effects in enhancing wound healing and hair
      growth.

PMID- 29057822
TI  - Risk Levels of Toxic Cyanobacteria in Portuguese Recreational Freshwaters.
AB  - Portuguese freshwater reservoirs are important socio-economic resources, namely
      for recreational use. National legislation concerning bathing waters does not
      include mandatory levels or guidelines for cyanobacteria and cyanotoxins. This is
      an issue of concern since cyanotoxin-based evidence is insufficient to change the
      law, and the collection of scientific evidence has been hampered by the lack of
      regulatory levels for cyanotoxins in bathing waters. In this work, we evaluate
      the profile of cyanobacteria and microcystins (MC) in eight freshwater reservoirs
      from the center of Portugal, used for bathing/recreation, in order to determine
      the risk levels concerning toxic cyanobacteria occurrence. Three of the
      reservoirs did not pose a risk of MC contamination. However, two reservoirs
      presented a high risk in 7% of the samples according to the World Health
      Organization (WHO) guidelines for MC in bathing waters (above 20 ug/L). In the
      remaining three reservoirs, the risk concerning microcystins occurrence was low.
      However, they exhibited recurrent blooms and persistent contamination with MC up
      to 4 ug/L. Thus, the risk of exposure to MC and potential acute and/or chronic
      health outcomes should not be disregarded in these reservoirs. These results
      contribute to characterize the cyanobacterial blooms profile and to map the risk
      of toxic cyanobacteria and microcystins occurrence in Portuguese inland waters.

PMID- 29057823
TI  - A New Cluster Analysis-Marker-Controlled Watershed Method for Separating
      Particles of Granular Soils.
AB  - An accurate determination of particle-level fabric of granular soils from
      tomography data requires a maximum correct separation of particles. The popular
      marker-controlled watershed separation method is widely used to separate
      particles. However, the watershed method alone is not capable of producing the
      maximum separation of particles when subjected to boundary stresses leading to
      crushing of particles. In this paper, a new separation method, named as Monash
      Particle Separation Method (MPSM), has been introduced. The new method
      automatically determines the optimal contrast coefficient based on cluster
      evaluation framework to produce the maximum accurate separation outcomes.
      Finally, the particles which could not be separated by the optimal contrast
      coefficient were separated by integrating cuboid markers generated from the
      clustering by Gaussian mixture models into the routine watershed method. The MPSM
      was validated on a uniformly graded sand volume subjected to one-dimensional
      compression loading up to 32 MPa. It was demonstrated that the MPSM is capable of
      producing the best possible separation of particles required for the fabric
      analysis.

PMID- 29057824
TI  - A DNA Structural Alphabet Distinguishes Structural Features of DNA Bound to
      Regulatory Proteins and in the Nucleosome Core Particle.
AB  - We analyzed the structural behavior of DNA complexed with regulatory proteins and
      the nucleosome core particle (NCP). The three-dimensional structures of almost 25
      thousand dinucleotide steps from more than 500 sequentially non-redundant crystal
      structures were classified by using DNA structural alphabet CANA (Conformational
      Alphabet of Nucleic Acids) and associations between ten CANA letters and sixteen
      dinucleotide sequences were investigated. The associations showed features
      discriminating between specific and non-specific binding of DNA to proteins.
      Important is the specific role of two DNA structural forms, A-DNA, and BII-DNA,
      represented by the CANA letters AAA and BB2: AAA structures are avoided in non
      specific NCP complexes, where the wrapping of the DNA duplex is explained by the
      periodic occurrence of BB2 every 10.3 steps. In both regulatory and NCP
      complexes, the extent of bending of the DNA local helical axis does not influence
      proportional representation of the CANA alphabet letters, namely the relative
      incidences of AAA and BB2 remain constant in bent and straight duplexes.

PMID- 29057825
TI  - Constitutive Equation and Hot Compression Deformation Behavior of Homogenized Al
      7.5Zn-1.5Mg-0.2Cu-0.2Zr Alloy.
AB  - The deformation behavior of homogenized Al-7.5Zn-1.5Mg-0.2Cu-0.2Zr alloy has been
      studied by a set of isothermal hot compression tests, which were carried out over
      the temperature ranging from 350  degrees C to 450  degrees C and the strain rate
      ranging from 0.001 s-1 to 10 s-1 on Gleeble-3500 thermal simulation machine. The
      associated microstructure was studied using electron back scattered diffraction
      (EBSD) and transmission electron microscopy (TEM). The results showed that the
      flow stress is sensitive to strain rate and deformation temperature. The shape of
      true stress-strain curves obtained at a low strain rate (<=0.1 s-1) conditions
      shows the characteristic of dynamic recrystallization (DRX). Two Arrhenius-typed
      constitutive equation without and with strain compensation were established based
      on the true stress-strain curves. Constitutive equation with strain compensation
      has more precise predictability. The main softening mechanism of the studied
      alloy is dynamic recovery (DRV) accompanied with DRX, particularly at deformation
      conditions, with low Zener-Holloman parameters.

PMID- 29057826
TI  - Potential Role of Phase Separation of Repetitive DNA in Chromosomal Organization.
AB  - The basic principles of chromosomal organization in eukaryotic cells remain
      elusive. Current mainstream research efforts largely concentrate on searching for
      critical packaging proteins involved in organizing chromosomes. I have taken a
      different perspective, by considering the role of genomic information in
      chromatins. In particular, I put forward the concept that repetitive DNA elements
      are key chromosomal packaging modules, and their intrinsic property of homology
      based interaction can drive chromatin folding. Many repetitive DNA families have
      high copy numbers and clustered distribution patterns in the linear genomes.
      These features may facilitate the interactions among members in the same repeat
      families. In this paper, the potential liquid-liquid phase transition of
      repetitive DNAs that is induced by their extensive interaction in chromosomes
      will be considered. I propose that the interaction among repetitive DNAs may lead
      to phase separation of interacting repetitive DNAs from bulk chromatins. Phase
      separation of repetitive DNA may provide a physical mechanism that drives rapid
      massive changes of chromosomal conformation.

PMID- 29057828
TI  - Theoretical Investigations of the Photophysical Properties of Star-Shaped pi
      Conjugated Molecules with Triarylboron Unit for Organic Light-Emitting Diodes
      Applications.
AB  - The density functional theory (DFT) and time-dependent DFT (TD-DFT) methodologies
      have been applied to explore on a series of star-shaped pi-conjugated organoboron
      systems for organic light-emitting diode (OLED) materials. The compounds under
      investigation consist of benzene as pi-bridge and different core units and
      triarylboron end groups. Their geometry structures, frontier molecular orbital
      (FMO) energies, absorption and fluorescence spectra, and charge transport
      properties have been investigated systematically. It turned out that the FMO
      energy levels, the band gaps, and reorganization energies optical are affected by
      the introduction of different core units and triarylboron end groups. The results
      suggest that the designed compounds are expected to be promising candidates for
      luminescent materials. Furthermore, they can also serve as hole and/or electron
      transport materials for OLEDs.

PMID- 29057827
TI  - Predictors Associated with Increase in Skeletal Muscle Mass after Sustained
      Virological Response in Chronic Hepatitis C Treated with Direct Acting
      Antivirals.
AB  - AIMS: We aimed to examine changes in skeletal muscle mass in chronic hepatitis C
      (CHC) patients undergoing interferon (IFN)-free direct acting antivirals (DAAs)
      therapy who achieved sustained virological response (SVR). PATIENTS AND METHODS:
      A total of 69 CHC patients treated with DAAs were analyzed. We compared the
      changes in skeletal muscle index (SMI) using bio-impedance analysis at baseline
      and SMI at SVR. SMI was calculated as the sum of skeletal muscle mass in upper
      and lower extremities divided by height squared (cm2/m2). Further, we identified
      pretreatment parameters contributing to the increased SMI at SVR. RESULTS: SMI in
      males at baseline ranged from 6.73 to 9.08 cm2/m2 (median, 7.65 cm2/m2), while
      that in females ranged from 4.45 to 7.27 cm2/m2 (median, 5.81 cm2/m2). At SVR, 36
      patients (52.2%) had increased SMI as compared with baseline. In the univariate
      analysis, age (p = 0.0392), hyaluronic acid (p = 0.0143), and branched-chain
      amino acid to tyrosine ratio (BTR) (p = 0.0024) were significant pretreatment
      factors linked to increased SMI at SVR. In the multivariate analysis, only BTR
      was an independent predictor linked to the increased SMI at SVR (p = 0.0488).
      CONCLUSION: Pretreatment BTR level can be helpful for predicting increased SMI
      after SVR in CHC patients undergoing IFN-free DAAs therapy.

PMID- 29057830
TI  - Time Response of Oxidative/Nitrosative Stress and Inflammation in LPS-Induced
      Endotoxaemia-A Comparative Study of Mice and Rats.
AB  - Sepsis is a severe and multifactorial disease with a high mortality rate. It
      represents a strong inflammatory response to an infection and is associated with
      vascular inflammation and oxidative/nitrosative stress. Here, we studied the
      underlying time responses in the widely used lipopolysaccharide (LPS)-induced
      endotoxaemia model in mice and rats. LPS (10 mg/kg; from Salmonella Typhosa) was
      intraperitoneally injected into mice and rats. Animals of every species were
      divided into five groups and sacrificed at specific points in time (0, 3, 6, 9,
      12 h). White blood cells (WBC) decreased significantly in both species after 3 h
      and partially recovered with time, whereas platelet decrease did not recover.
      Oxidative burst and iNOS-derived nitrosyl-iron hemoglobin (HbNO) increased with
      time (maxima at 9 or 12 h). Immune cell infiltration (CD68 and F4/80 content)
      showed an increase with time, which was supported by increased vascular mRNA
      expression of VCAM-1, P-selectin, IL-6 and TNF-alpha. We characterized the time
      responses of vascular inflammation and oxidative/nitrosative stress in LPS
      induced endotoxaemic mice and rats. The results of this study will help to
      interpret and compare data from different animal species in LPS-induced
      endotoxaemia models for the identification of new drug targets.

PMID- 29057831
TI  - The Heartrate Reaction to Acute Stress in Horned Passalus Beetles (Odontotaenius
      disjunctus) is Negatively Affected by a Naturally-Occurring Nematode Parasite.
AB  - There are many events in the lives of insects where rapid, effective stress
      reactions are needed, including fighting conspecifics to defend territories,
      evading predators, and responding to wounds. A key element of the stress reaction
      is elevation of heartrate (HR), for enhancing distribution of blood (hemolymph)
      to body compartments. We conducted two experiments designed to improve
      understanding of the insect stress reaction and how it is influenced by
      parasitism in a common beetle species (Odontotaenius disjunctus). By non
      destructively observing heartbeat frequency before, during and after applying a
      stressor (physical restraint) for 10 min, we sought to determine: (1) the exact
      timing of the cardiac stress reaction; (2) the magnitude of heartrate elevation
      during stress; and (3) if the physiological response is affected by a naturally
      occurring nematode parasite, Chondronema passali. Restraint caused a dramatic
      increase in heartrate, though not immediately; maximum HR was reached after
      approximately 8 min. Average heartrate went from 65.5 beats/min to a maximum of
      81.5 (24.5% increase) in adults raised in the lab (n = 19). Using wild-caught
      adults (n = 77), average heartrates went from 54.9 beats/min to 74.2 (35.5%
      increase). When restraint was removed, HR declined after ~5 min, and reached
      baseline 50 min later. The nematode parasite did not affect baseline heartrates
      in either experiment, but in one, it retarded the heartrate elevation during
      stress, and in the other, it reduced the overall magnitude of the elevation.
      While we acknowledge that our results are based on comparisons of beetles with
      naturally-occurring parasite infections, these results indicate this parasite
      causes a modest reduction in host cardiac output during acute stress conditions.

PMID- 29057829
TI  - Association of Vitamin E Levels with Metabolic Syndrome, and MRI-Derived Body Fat
      Volumes and Liver Fat Content.
AB  - We aimed to relate circulating alpha- and gamma-tocopherol levels to a broad
      spectrum of adiposityrelated traits in a cross-sectional Northern German study.
      Anthropometric measures were obtained, and adipose tissue volumes and liver fat
      were quantified by magnetic resonance imaging in 641 individuals (mean age 61
      years; 40.6% women). Concentrations of alpha- and gamma-tocopherol were measured
      using high performance liquid chromatography. Multivariable-adjusted linear and
      logistic regression were used to assess associations of circulating alpha- and
      gamma-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous
      adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD),
      metabolic syndrome (MetS), and its individual components. The alpha-
      tocopherol/cholesterol ratio was positively associated with VAT (beta scaled by
      interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and
      MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21-2.76 for 3rd vs. 1st tertile), and the
      gamma-tocopherol/cholesterol ratio was positively associated with VAT (beta
      scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (beta scaled by IQR: 0.048; 95%
      CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23-2.84 for 3rd vs. 1st tertile).
      alpha- and gamma-tocopherol levels were positively associated with high
      triglycerides and low high density lipoprotein cholesterol levels (all Ptrend <
      0.05). No association of alpha- and gamma-tocopherol/cholesterol ratio with
      LSI/FLD was observed. Circulating vitamin E levels displayed strong associations
      with VAT and MetS. These observations lay the ground for further investigation in
      longitudinal studies.

PMID- 29057832
TI  - Structure, Absolute Configuration, and Antiproliferative Activity of Abietane and
      Icetexane Diterpenoids from Salvia ballotiflora.
AB  - From the aerial parts of Salvia ballotiflora, eleven diterpenoids were isolated;
      among them, four icetexanes and one abietane (1-5) are reported for the first
      time. Their structures were established by spectroscopic means, mainly 1H- and
      13C-NMR, including 1D and 2D homo- and hetero-nuclear experiments. Most of the
      isolated diterpenoids were tested for their antiproliferative, anti-inflammatory,
      and radical scavenging activities using the sulforhodamine B assay on six cancer
      cell lines, the TPA-induced ear edema test in mice, and the reduction of the DPPH
      assay, respectively. Some diterpenoids showed anti-proliferative activity, these
      being icetexanes 6 and 3, which were the most active with IC50 (MUM) = 0.27 +/-
      0.08 and 1.40 +/- 0.03, respectively, for U251 (human glioblastoma) and IC50
      (MUM) = 0.0.46 +/- 0.05 and 0.82 +/- 0.06 for SKLU-1 (human lung adenocarcinoma),
      when compared with adriamycin (IC50 (MUM) = 0.08 +/- 0.003 and 0.05 +/- 0.003, as
      the positive control), respectively. Compounds 3 and 10 showed significant
      reduction of the induced ear edema of 37.4 +/- 2.8 and 25.4 +/- 3.0% (at 1.0
      MUmol/ear), respectively. Compound 4 was the sole active diterpenoid in the
      antioxidant assay (IC50 = 98. 4 +/- 3.3), using alpha-tocopherol as the positive
      control (IC50 (MUM) = 31.7 +/- 1.04). The diterpenoid profile found is of
      chemotaxonomic relevance and reinforces the evolutionary link of S. ballotiflora
      with other members of the section Tomentellae.

PMID- 29057833
TI  - Indications and Use of the Gluten Contamination Elimination Diet for Patients
      with Non-Responsive Celiac Disease.
AB  - For the majority of patients diagnosed with celiac disease, once a gluten-free
      diet is initiated, symptoms improve within weeks and may completely resolve in
      months. However, up to 30% of patients may show signs, symptoms or persistent
      small intestinal damage after one year on a gluten-free diet. These patients
      require evaluation for other common GI etiologies and assessment of their celiac
      disease status in order to make a diagnosis and suggest treatment. Here, we
      propose an approach to evaluating patients with celiac disease with persistent
      symptoms, persistently elevated serology, and or persistent villous atrophy
      despite a gluten-free diet. We detail how to diagnose and distinguish between non
      responsive and refractory celiac disease. Finally, we introduce the indications
      for use of the gluten contamination elimination diet and provide information for
      practitioners to implement the diet when necessary in their practice.

PMID- 29057834
TI  - Non-Alcoholic Fatty Liver Disease and Nutritional Implications: Special Focus on
      Copper.
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by excess lipids in
      hepatocytes, due to excessive fatty acid influx from adipose tissue, de novo
      hepatic lipogenesis, in addition to excessive dietary fat and carbohydrate
      intake. Chronic hepatic lipid overload induces mitochondrial oxidative stress and
      cellular damage leading the development of NAFLD into a more severe liver disease
      condition, non-alcoholic steato-hepatitis (NASH). In turn, this can progress to
      cirrhosis and hepatocellular carcinoma (HCC). Among others, copper is one of the
      main bio-metals required for the preponderance of the enzymes involved in
      physiological redox reactions, which primarily occurs during mitochondrial
      respiration. Thus, copper homeostasis could be considered a target point for
      counteracting the progression of NAFLD. Accordingly, many diseases are correlated
      to unbalanced copper levels and, actually, some clinical trials are examining the
      use of copper chelating agents. Currently, no pharmacological interventions are
      approved for NAFLD, but nutritional and lifestyle modifications are always
      recommended. Fittingly, antioxidant food agents recognized to improve NAFLD and
      its complications have been described in the literature to bind copper.
      Therefore, this review describes the role of nutrition in the development and
      progression of NAFLD with a particular focus on copper and copper-binding
      antioxidant compounds against NAFLD.

PMID- 29057835
TI  - Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing
      Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in
      Weaned Rats.
AB  - Individuals who consume a diet deficient in zinc (Zn-deficient) develop
      alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low
      metabolic rate and cold insensitivity. Although those disturbances are related to
      primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an
      increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH)
      levels and decreased body weight. This does not support the view that the
      hypothyroidism develops due to a low Zn intake. In addition, intrauterine or
      postnatal Zn-deficiency in weaned and adult rats reduces the activity of
      pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH).
      PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This
      hypothalamic peptide stimulates its receptor in adenohypophysis, thereby
      increasing TSH release. We analyzed whether earlier low TH is responsible for the
      high TSH levels reported in adults, or if TRH release is enhanced by Zn
      deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from
      one week prior to gestation and up to three weeks after delivery. We found a high
      release of hypothalamic TRH, which along with reduced MBH PPII activity,
      increased TSH levels in Zn-deficient pups independently of changes in TH
      concentration. We found that primary hypothyroidism did not develop in
      intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency
      enhances TSH levels since early-life, favoring subclinical hypothyroidism
      development which remains into adulthood.

PMID- 29057836
TI  - Citrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in
      Untrained Young Adult Men.
AB  - The effects of citrulline malate (CM) on muscle recovery from resistance exercise
      remains unknown. We aimed to determine if citrulline malate supplementation
      improves muscle recovery after a single session of high-intensity resistance
      exercise (RE) in untrained young adult men. Nine young adult men (24.0 +/- 3.3
      years) participated in a double-blind crossover study in which they received 6 g
      of CM and placebo (PL) on two occasions, separated by a seven-day washout period.
      Each occasion consisted of a single session of high-intensity RE (0 h) and three
      subsequent fatigue tests sessions (at 24, 48, and 72 h) to assess the time course
      of muscle recovery. During the tests sessions, we assessed the following
      variables: number of maximum repetitions, electromyographic signal (i.e., root
      mean square (RMS) and median frequency (MF)), muscle soreness and perceived
      exertion, as well as blood levels of creatine kinase (CK), lactate, insulin, and
      testosterone:cortisol ratio. CK levels increased at 24 h post-exercise and
      remained elevate at 48 and 72 h, with no difference between CM and PL conditions.
      Muscle soreness increased at 24 h post-exercise, which progressively returned to
      baseline at 72 h in both conditions. Lactate levels increased immediately post
      exercise and remained elevated at 24, 48, and 72 h in both conditions. No
      significant treatment * time interaction was found for all dependents variables
      (maximum repetitions, perceived exertion, CK, lactate, RMS, MF, and
      testosterone:cortisol ratio) during the recovery period. In conclusion, our data
      indicate that CM supplementation (single 6 g dose pre-workout) does not improve
      the muscle recovery process following a high-intensity RE session in untrained
      young adult men.

PMID- 29057837
TI  - Magnetron Sputtering as a Fabrication Method for a Biodegradable Fe32Mn Alloy.
AB  - Biodegradable metals are a topic of great interest and Fe-based materials are
      prominent examples. The research task is to find a suitable compromise between
      mechanical, corrosion, and magnetic properties. For this purpose, investigations
      regarding alternative fabrication processes are important. In the present study,
      magnetron sputtering technology in combination with UV-lithography was used in
      order to fabricate freestanding, microstructured Fe32Mn films. To adjust the
      microstructure and crystalline phase composition with respect to the
      requirements, the foils were post-deposition annealed under a reducing
      atmosphere. The microstructure and crystalline phase composition were
      investigated by scanning electron microscopy, energy dispersive X-ray
      spectroscopy, and X-ray diffraction. Furthermore, for mechanical
      characterization, uniaxial tensile tests were performed. The in vitro corrosion
      rates were determined by electrochemical polarization measurements in pseudo
      physiological solution. Additionally, the magnetic properties were measured via
      vibrating sample magnetometry. The foils showed a fine-grained structure and a
      tensile strength of 712 MPa, which is approximately a factor of two higher
      compared to the sputtered pure Fe reference material. The yield strength was
      observed to be even higher than values reported in literature for alloys with
      similar composition. Against expectations, the corrosion rates were found to be
      lower in comparison to pure Fe. Since the annealed foils exist in the austenitic,
      and antiferromagnetic gamma-phase, an additional advantage of the FeMn foils is
      the low magnetic saturation polarization of 0.003 T, compared to Fe with 1.978 T.
      This value is even lower compared to the SS 316L steel acting as a gold standard
      for implants, and thus enhances the MRI compatibility of the material. The study
      demonstrates that magnetron sputtering in combination with UV-lithography is a
      new concept for the fabrication of already in situ geometrically structured FeMn
      based foils with promising mechanical and magnetic properties.

PMID- 29057838
TI  - The Potential Impact of Satellite-Retrieved Cloud Parameters on Ground-Level
      PM2.5 Mass and Composition.
AB  - Satellite-retrieved aerosol optical properties have been extensively used to
      estimate ground-level fine particulate matter (PM2.5) concentrations in support
      of air pollution health effects research and air quality assessment at the urban
      to global scales. However, a large proportion, ~70%, of satellite observations of
      aerosols are missing as a result of cloud-cover, surface brightness, and snow
      cover. The resulting PM2.5 estimates could therefore be biased due to this non
      random data missingness. Cloud-cover in particular has the potential to impact
      ground-level PM2.5 concentrations through complex chemical and physical
      processes. We developed a series of statistical models using the Multi-Angle
      Implementation of Atmospheric Correction (MAIAC) aerosol product at 1 km
      resolution with information from the MODIS cloud product and meteorological
      information to investigate the extent to which cloud parameters and associated
      meteorological conditions impact ground-level aerosols at two urban sites in the
      US: Atlanta and San Francisco. We find that changes in temperature, wind speed,
      relative humidity, planetary boundary layer height, convective available
      potential energy, precipitation, cloud effective radius, cloud optical depth, and
      cloud emissivity are associated with changes in PM2.5 concentration and
      composition, and the changes differ by overpass time and cloud phase as well as
      between the San Francisco and Atlanta sites. A case-study at the San Francisco
      site confirmed that accounting for cloud-cover and associated meteorological
      conditions could substantially alter the spatial distribution of monthly ground
      level PM2.5 concentrations.

PMID- 29057839
TI  - Correlation of Structure, Tunable Colors, and Lifetimes of (Sr, Ca,
      Ba)Al2O4:Eu2+, Dy3+ Phosphors.
AB  - (Sr, Ca, Ba)Al2O4:Eu2+, Dy3+ phosphors were prepared via a high temperature solid
      state reaction method. The correlation of phase structure, optical properties and
      lifetimes of the phosphors are investigated in this work. For the (Sr,
      Ca)Al2O4:Eu2+,Dy3+ phosphors, the different phase formation from monoclinic
      SrAl2O4 phase to hexagonal SrAl2O4 phase to monoclinic CaAl2O4 phase was observed
      when the Ca content increased. The emission color of SrAl2O4:Eu2+, Dy3+ phosphors
      varied from green to blue. For the (Sr, Ba)Al2O4:Eu2+, Dy3+ phosphors, different
      phase formation from the monoclinic SrAl2O4 phase to the hexagonal BaAl2O4 phase
      was observed, along with a shift of emission wavelength from 520 nm to 500 nm.
      More interestingly, the decay time of SrAl2O4:Eu2+, Dy3+changed due to the
      different phase formations. Lifetime can be dramatically shortened by the
      substitution of Sr2+ with Ba2+ cations, resulting in improving the performance of
      the alternating current light emitting diode (AC-LED). Finally, intense LEDs are
      successfully obtained by combining these phosphors with Ga(In)N near UV chips.

PMID- 29057840
TI  - Ethnomedicinal, Phytochemical and Ethnopharmacological Aspects of Four Medicinal
      Plants of Malvaceae Used in Indian Traditional Medicines: A Review.
AB  - The ethnomedicinal values of plants form the basis of the herbal drug industry.
      India has contributed its knowledge of traditional system medicines (Ayurveda and
      Siddha) to develop herbal medicines with negligible side effects. The World
      Health Organization has also recognized the benefits of drugs developed from
      natural products. Abutilon indicum, Hibiscus sabdariffa, Sida acuta and Sida
      rhombifolia are ethnomedicinal plants of Malvaceae, commonly used in Indian
      traditional system of medicines. Traditionally these plants were used in the form
      of extracts/powder/paste by tribal populations of India for treating common
      ailments like cough and cold, fever, stomach, kidney and liver disorders, pains,
      inflammations, wounds, etc. The present review is an overview of phytochemistry
      and ethnopharmacological studies that support many of the traditional
      ethnomedicinal uses of these plants. Many phytoconstituents have been isolated
      from the four ethnomedicinal plants and some of them have shown pharmacological
      activities that have been demonstrated by in vivo and/or in vitro experiments.
      Ethnomedicinal uses, supported by scientific evidences is essential for ensuring
      safe and effective utilization of herbal medicines.

PMID- 29057841
TI  - Review of Black Soldier Fly (Hermetia illucens) as Animal Feed and Human Food.
AB  - Food futurists accept that sustainability-minded humanity will increasingly
      incorporate insects as alternative protein. The most studied and easily reared
      species are not necessarily the most sustainable, acceptable, or delicious. Here,
      we review the literature on the black soldier fly, Hermetia illucens, which is
      capable of efficiently converting a wide variety of organic materials, from food
      waste to manure, into insect biomass. They can be grown and harvested without
      dedicated facilities and are not pestiferous. Their larvae are 42% crude protein
      and 29% fat, although they are higher in saturated fats than most insects. They
      do not concentrate pesticides or mycotoxins. They are already grown and
      recommended for use as animal feed, but with regional legal restrictions on how
      this is done. For commercial use in human foods, larvae could potentially be
      milled and converted into a textured protein with a strong flavor. Their biggest
      advantage over other insects is their ability to convert waste into food,
      generating value and closing nutrient loops as they reduce pollution and costs.
      This general advantage is also their greatest disadvantage, for the social
      stigmas and legal prohibitions against eating organisms that eat waste are added
      to extant taboos facing insect consumption.

PMID- 29057842
TI  - Qualitative Studies of Infant and Young Child Feeding in Lower-Income Countries:
      A Systematic Review and Synthesis of Dietary Patterns.
AB  - Continued high rates of both under- and over-nutrition in low- and low-middle
      income countries highlight the importance of understanding dietary practices such
      as early and exclusive breastfeeding, and dietary patterns such as timely,
      appropriate complementary feeding-these behaviors are rooted in complex cultural
      ecologies. A systematic review and synthesis of available qualitative research
      related to infant and young child dietary patterns and practices from the
      perspective of parents and families in low income settings is presented, with a
      focus on barriers and facilitators to achieving international recommendations.
      Data from both published and grey literature from 2006 to 2016 was included in
      the review. Quality assessment consisted of two phases (Critical Appraisal Skills
      Program (CASP) guidelines and assessment using GRADE-CERQual), followed by
      synthesis of the studies identified, and subsequent thematic analysis and
      interpretation. The findings indicated several categories of both barriers and
      facilitators, spanning individual and system level factors. The review informs
      efforts aimed at improving child health and nutrition, and represents the first
      such comprehensive review of the qualitative literature, uniquely suited to
      understanding complex behaviors leading to infant and young child dietary
      patterns.

PMID- 29057843
TI  - Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A
      Systematic Review and Network Meta-Analysis.
AB  - Vitamin D supplementation effects with or without calcium in pregnancy for
      reducing risk of preeclampsia and gestational or pregnancy induced hypertension
      are controversial. Literature was systematically searched in Medline, Scopus and
      Cochrane databases from inception to July 2017. Only randomized controlled trials
      (RCTs) in English were selected if they had any pair of interventions (calcium,
      vitamin D, both, or placebo). Systematic review with two-step network-meta
      analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs
      with 28,000 women were eligible. A direct meta-analysis suggested that calcium,
      vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when
      compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47
      (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta
      analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43
      (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were
      significant. Efficacy of supplementation, which was ranked by surface under
      cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and
      calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used
      for prevention for preeclampsia. Vitamin D might also worked well but further
      large scale RCTs are warranted to confirm our findings.

PMID- 29057844
TI  - Functional Characterization of Rare RAB12 Variants and Their Role in Musician's
      and Other Dystonias.
AB  - Mutations in RAB (member of the Ras superfamily) genes are increasingly
      recognized as cause of a variety of disorders including neurological conditions.
      While musician's dystonia (MD) and writer's dystonia (WD) are task-specific
      movement disorders, other dystonias persistently affect postures as in cervical
      dystonia. Little is known about the underlying etiology. Next-generation
      sequencing revealed a rare missense variant (c.586A>G; p.Ile196Val) in RAB12 in
      two of three MD/WD families. Next, we tested 916 additional dystonia patients;
      512 Parkinson's disease patients; and 461 healthy controls for RAB12 variants and
      identified 10 additional carriers of rare missense changes among dystonia
      patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p =
      0.005). The detected variants among index patients comprised p.Ile196Val (n = 6);
      p.Ala174Thr (n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with
      MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried
      p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp)
      were characterized on endogenous levels in patient-derived fibroblasts and in two
      RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate
      (GTP), so called GTPase activity, was increased in mutants compared to wildtype.
      Furthermore, subcellular distribution of RAB12 in mutants was altered in
      fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of
      all three tested p.Ile196Val carriers. In conclusion, we demonstrate an
      enrichment of missense changes among dystonia patients. Functional
      characterization revealed altered enzyme activity and lysosomal distribution in
      mutants suggesting a contribution of RAB12 variants to MD and other dystonias.

PMID- 29057845
TI  - Variations of Escherichia coli O157:H7 Survival in Purple Soils.
AB  - Escherichia coli O157:H7 is a well-recognized cause of human illness. Survival of
      Escherichia coli O157:H7 in five purple soils from Sichuan Province was
      investigated. The dynamics of E. coli O157:H7 survival in purple soils were
      described by the Weibull model. Results showed that this model is suitable to fit
      survival curves of E. coli O157:H7 in purple soils, with the calculated td value
      (survival time needed to reach the detection limit of 100 CFU.g-1) ranging from
      2.99 days to 26.36 days. The longest survival time of E. coli O157:H7 was
      observed in neutral purple soils (24.49 days), followed by alkalescent purple
      soil (18.62 days) and acid purple soil (3.48 days). The redundancy analysis (RDA)
      revealed that td values were significantly enhanced by soil nutrition (total
      organic carbon (OC), total nitrogen (TN), available potassium (AK) and the ratio
      of humic acid to fulvic acid (Ha/Fa)), but were significantly suppressed by iron
      and aluminum oxide.

PMID- 29057847
TI  - Time Series UAV Image-Based Point Clouds for Landslide Progression Evaluation
      Applications.
AB  - Landslides are major and constantly changing threats to urban landscapes and
      infrastructure. It is essential to detect and capture landslide changes
      regularly. Traditional methods for monitoring landslides are time-consuming,
      costly, dangerous, and the quality and quantity of the data is sometimes unable
      to meet the necessary requirements of geotechnical projects. This motivates the
      development of more automatic and efficient remote sensing approaches for
      landslide progression evaluation. Automatic change detection involving low
      altitude unmanned aerial vehicle image-based point clouds, although proven, is
      relatively unexplored, and little research has been done in terms of accounting
      for volumetric changes. In this study, a methodology for automatically deriving
      change displacement rates, in a horizontal direction based on comparisons between
      extracted landslide scarps from multiple time periods, has been developed.
      Compared with the iterative closest projected point (ICPP) registration method,
      the developed method takes full advantage of automated geometric measuring,
      leading to fast processing. The proposed approach easily processes a large number
      of images from different epochs and enables the creation of registered image
      based point clouds without the use of extensive ground control point information
      or further processing such as interpretation and image correlation. The produced
      results are promising for use in the field of landslide research.

PMID- 29057846
TI  - Magnetic Fields and Reactive Oxygen Species.
AB  - Reactive oxygen species (ROS) ubiquitously exist in mammalian cells to
      participate in various cellular signaling pathways. The intracellular ROS levels
      are dependent on the dynamic balance between ROS generation and elimination. In
      this review, we summarize reported studies about the influences of magnetic
      fields (MFs) on ROS levels. Although in most cases, MFs increased ROS levels in
      human, mouse, rat cells, and tissues, there are also studies showing that ROS
      levels were decreased or not affected by MFs. Multiple factors could cause these
      discrepancies, including but not limited to MF type/intensity/frequency, exposure
      time and assay time-point, as well as different biological samples examined. It
      will be necessary to investigate the influences of different MFs on ROS in
      various biological samples systematically and mechanistically, which will be
      helpful for people to get a more complete understanding about MF-induced
      biological effects. In addition, reviewing the roles of MFs in ROS modulation may
      open up new scenarios of MF application, which could be further and more widely
      adopted into clinical applications, particularly in diseases that ROS have
      documented pathophysiological roles.

PMID- 29057848
TI  - Genistein Binding to Copper(II)-Solvent Dependence and Effects on Radical
      Scavenging.
AB  - Genistein, but not daidzein, binds to copper(II) with a 1:2 stoichiometry in
      ethanol and with a 1:1 stoichiometry in methanol, indicating chelation by the 5
      phenol and the 4-keto group of the isoflavonoid as demonstrated by the Jobs
      method and UV-visible absorption spectroscopy. In ethanol, the stability
      constants had the value 1.12 * 1011 L2?mol-2 for the 1:2 complex and in methanol
      6.0 * 105 L?mol-1 for the 1:1 complex at 25  degrees C. Binding was not detected
      in water, as confirmed by an upper limit for the 1:1 stability constant of K = 5
      mol-1 L as calculated from the difference in solvation free energy of copper(II)
      between methanol and the more polar water. Solvent molecules compete with
      genistein as demonstrated in methanol where binding stoichiometry changes from
      1:2 to 1:1 compared to ethanol and methanol/chloroform (7/3, v/v). Genistein
      binding to copper(II) increases the scavenging rate of the stable, neutral 2,2
      diphenyl-1-picrylhydrazyl radical by more than a factor of four, while only small
      effects were seen for the short-lived but more oxidizing beta-carotene radical
      cation using laser flash photolysis. The increased efficiency of coordinated
      genistein is concluded to depend on kinetic rather than on thermodynamic factors,
      as confirmed by the small change in reduction potential of -0.016 V detected by
      cyclic voltammetry upon binding of genistein to copper(II) in methanol/chloroform
      solutions.

PMID- 29057849
TI  - A Closer Look at Angiitis of the central nervous system.
AB  - Angiitis of the central nervous system (ACNS) is a rather new disease entity that
      is defined as vascular inflammation limited to the central nervous system and was
      formally nominated in 1959. Etiologically, it can be divided into primary and
      secondary ACNS. However, the potential pathogenesis of ACNS remains unclear. The
      clinical presentation is variable, and there is no consensus concerning its
      diagnosis and management. Although the incidence is relatively low, ACNS is still
      a life-threatening condition. It is essential to get a comprehensive and updated
      understanding of the disease. In this paper, we reviewed the history, definition,
      classification, pathogenesis, and clinical manifestations of ACNS. In addition,
      we focused on the latest investigations and viewpoints regarding the diagnosis
      and treatment of ACNS.

PMID- 29057850
TI  - Quality of life among multiple sclerosis patients in Saudi Arabia.
AB  - OBJECTIVE: To assess quality of life in multiple sclerosis (MS) patients and
      determine the factors associated with levels of quality of life in MS patients in
      a public hospital in Saudi Arabia. METHODS: A cross-sectional study was conducted
      from June 2016 to April 2017 in King Abdulaziz Medical City, Jeddah, Kingdom of
      Saudi Arabia. Multiple sclerosis patients attending the outpatient and inpatient
      services were approached and recruited to participate in the study. The Arabic
      version of EuroQOL-5 Dimensions instrument (EQ-5D) was utilized for the
      assessment of MS patients quality of life. RESULTS: Data on quality of life were
      obtained from 292 patients. The reported quality of life of MS patients as
      measured by the EQ-5D index value score was 0.31+/-0.51 and the EQ-VAS score was
      73.87+/-23.41, respectively. It was found that quality of life determined
      numerically in the EQ-5D index value and EQ-VAS deteriorates proportionally
      according to the disease duration. CONCLUSION: Multiple sclerosis is associated
      with a considerable effect on the patients quality of life. It continues to be
      challenging to manage both medically and psychosocially. Clinicians should
      consider the assessment of quality of life as routine practice along with the
      other important measures including symptomatic evaluation, laboratory tests, and
      neuroimaging to provide a holistic care of their MS patients.

PMID- 29057852
TI  - Tumors of the lateral and third ventricle: surgical management and outcome
      analysis in 42 cases.
AB  - OBJECTIVE: To discuss the clinical presentation, pathological diagnosis, and
      surgical outcome for a series of 42 consecutive patients treated for lateral and
      third ventricular tumors. METHODS: This is a retrospective series study conducted
      between 2001 and 2015 and included 42 patients (mean age: 25 years; range: 2
      months-65 years) with lateral and third ventricle tumors surgically treated at
      King Khaled University Hospital, Riyadh, Kingdom of Saudi Arabia. Demographic,
      clinical, radiological, surgical, histopathological, and follow up data were
      analyzed. RESULTS: The most common symptoms at presentation included headache
      (69%), nausea/vomiting (38%), visual deficits (24%), and seizures (17%). Lesions
      were located in the lateral ventricle in 15 patients, third ventricle in 20
      patients, and involved both the lateral and third ventricles in 7 patients. The
      most common tumor types in the overall cohort were colloid cysts (n=6) and pineal
      tumors (n=6). The postoperative complication rate was 36%. The most common
      postoperative complications were seizure and hydrocephalus (n=5 each, 12%).
      Surgical mortality was 5%. CONCLUSION: The selection of the surgical approach for
      intraventricular tumor resection is fundamentally dependent on the surgeon's
      experience and preference. We recommend that this decision be based on the
      anatomic considerations that provide the best and safest access to the mass,
      rather than on the risk of seizure following transcortical approach.

PMID- 29057851
TI  - Type and etiology of pediatric epilepsy in Jordan. A multi-center study.
AB  - OBJECTIVE: To study types and etiologies of epilepsy in Jordanian pediatric
      epileptic patients maintained on antiepileptic drugs using customized
      classification scheme of International League Against Epilepsy (ILAE) (2010)
      report. METHODS: This is a cross-sectional, multi-centre study on pediatric
      epileptic patients on antiepileptic drugs, who were managed in the pediatric
      neurology clinics at 6 teaching public hospitals in Jordan. RESULTS: Out of the
      663 patients included in the study, (90.2%) had one seizure type, (53%) of this
      type were focal seizures followed by generalized seizures (41.5%) and spasms
      (5.5%). Distinctive constellations were found in 11/663 (1.7%) patients. Benign
      epilepsies with centrotemporal spikes were the most common electro clinical
      syndromes 60/221 (27.1%). Epilepsies attributed to structural-metabolic causes
      were documented in 278/663 (41.9%) patients, unknown causes 268/663(40.4%) and
      genetic causes in 117/663(17.7%). Most common causes of structural-metabolic
      group were due to perinatal insults (32%) and most common causes of the genetic
      group were the presumed genetic electro clinical syndromes (93.1%). CONCLUSION:
      Our study is on pediatric epilepsy, using customized classification scheme from
      the ILAE 2010 report which showed interesting results about type and etiology of
      epileptic seizures from developing country with potential impact on the
      international level.

PMID- 29057853
TI  - Dental caries and related risk factors in Saudi cerebral palsy children.
AB  - OBJECTIVE: To determine caries experience and related risk factors in cerebral
      palsy (CP) children. METHODS: Random sample of CP children was examined for
      dental caries and oral hygiene. Questionnaire was utilized for information about
      caries risk factors. This cross-sectional study was conducted in Riyadh from
      December 2014 to May 2015. RESULTS: Fifty-two CP children were examined with mean
      age of 6.3+/-2.7 years. Only one (1.9%) child out of the 52 had no clinical
      caries. Combined (dmft plus DMFT) mean caries score among study sample was 9.98+/
      3.99. Older children had significantly higher mean caries scores (11.5+/-3.34)
      than younger children (8.86+/-4.1, p=0.017). The CP children with good oral
      hygiene had lowest mean caries score (5.8+/-7.32) as compared to those with fair
      (9.72+/-3.3) and poor (11.55+/-3.05) oral hygiene (p=0.012). Those children whose
      first dental visit was for routine check-up had significantly (p=0.02) lower mean
      caries scores (7.33+/-4.65) than those who made their first visit due to dental
      problem (11.57+/-4.15). Similarly, those who had topical fluoride applications by
      dentist had significantly (p=0.003) lower mean caries scores (8.67+/-4.14) than
      those with no topical fluoride application (11.9+/-2.89). CONCLUSION: The studied
      CP children had very high caries experience and poor oral hygiene. There was
      strong association between the high caries experience and poor oral hygiene.

PMID- 29057854
TI  - Frontal theta/beta ratio changes during TOVA in Egyptian ADHD children.
AB  - OBJECTIVE: To spot the frontal theta/beta ratio alterations during Tests of
      Variance of Attention (TOVA) in Egyptian attention deficit hyperactivity disorder
      (ADHD) children. METHODS: This is a cross sectional study performed in Clinical
      Neurophysiology Unit, Cairo University, Egypt. It included 2 groups, each of 52
      children (one of them with ADHD and the other were normal control). EEG was
      recorded for every subject during normal relaxing circumstance with eyes opened
      as well as during TOVA. RESULTS: Comparing both groups revealed statistically
      significant difference in the theta/beta ratio in both state (normal relaxing
      with eyes opened and during TOVA), also we found that the theta/beta ratio
      decreased in normal group (during concentration) while in the ADHD group it
      increased with a specific pattern. CONCLUSION: The theta/beta ratio can be of
      value in helping for differential diagnosis in patients presenting with mild
      ADHD.

PMID- 29057855
TI  - A rare case of autoimmune limbic encephalitis: an uncharted territory!
AB  - Autoimmune encephalitis is rare. Several auto- antibodies are described in
      autoimmune encephalitis. We describe a case of autoimmune limbic encephalitis
      associated with positive voltage gated potassium channel (VGKC) antibodies and
      positive leucine-rich glioma inactivated protein 1 antibodies (LGI1). A 33-year
      old Saudi housewife, she presented with 2 months history of cognitive
      deterioration and recurrent left facio-brachial dystonic seizures followed by
      generalized tonic clonic seizures. At times the seizures are preceded by rising
      epigastric aura and shortness of breath. The neurological examination was normal
      apart from upgoing left plantar reflex. She had borderline IQ of 76 with impaired
      verbal fluency and impaired visual and verbal memory. Magnetic resonance imaging
      of the brain showed right mesial temporal non-enhancing lesion. Cerebrospinal
      fluid examination was positive for LGI1 and VGKC. Optimal seizure control was
      achieved with immunotherapy.

PMID- 29057856
TI  - Migration of the distal catheter of the ventriculoperitoneal shunt in
      hydrocephalus patients.
AB  - Distal catheter migration of a ventriculoperitoneal shunt (VPS) is a rare but
      serious complication. It is usually asymptomatic. However, it can be further
      complicated by the presence of co-infections, interruption of the shunt, and/or
      disturbances in penetrated organ function. In this report, we presented a case of
      spontaneous complete extrusion of the distal end of a VPS catheter through the
      intact abdominal wall in a 5-year-old boy with hydrocephalus. We also reviewed
      and analyzed the literature for similar cases of complete extrusion of the distal
      end of a VPS catheter, through an intact or a potential weakness in the body
      wall, in the last 20 years. From the reviewed literature, we did not observe any
      difference (p>0.05) in the incidence of this complication between cases with an
      intact or a potential weakness in the body wall.

PMID- 29057858
TI  - Development of Parkinsonism symptoms immediately after severe head injury.
AB  - This is case report of a young adult male who had developed Parkinsonism symptoms
      shortly after severe head injury due to accidental fall. This 45-year-old man was
      diagnosed as multiple hemorrhagic contusions, sub arachnoid hemorrhage and linear
      skull fracture. After 4 weeks of fall, he developed Parkinsonian symptoms which
      were relieved by anti-parkinsons disease medication. After doing thorough journal
      review only few reports were found regarding short term onset of Parkinsons
      disease after severe head injury, though most of the literatures evident of the
      similar symptoms after more than years after the head trauma.

PMID- 29057857
TI  - Case series of autosomal recessive hereditary spastic paraparesis with novel
      mutation in SPG 7 gene.
AB  - Autosomal recessive hereditary spastic paraparesis is rare.We present 4 patients
      with slowly progressive predominantly lower limb spasticity and ataxia. Only one
      patient had family history of ataxia but without any underlying diagnosis. All of
      them proved negative for the mutation of Spinocerebelalr ataxia genes SCA 1,2,3
      and 6. All had mutation in the SPG 7 gene suggestive of autosomal recessive
      hereditary spastic paraparesis. One of the heterozygous mutatnts showed a novel
      c1617delC ,p(Val540fs) frameshift mutation in exon 12 of the SPG 7 gene. SPG7
      mutation accounts for 1.5-7% of all the HSP but it is the cause of undiagnosed
      ataxia in 18.6% in a recent case series. SPG7 mutation should be remembered as an
      important cause of undiagnosed ataxia especially where next generation sequencing
      is not widely avaialbale or affordable.

PMID- 29057859
TI  - Neurological manifestations, laboratory and neuroimaging features in HIV-infected
      patients.
AB  - OBJECTIVE: To present detailed information regarding these aspects in Human
      Immunodeficiency Virus (HIV)-infected patients making an effort to improve the
      recognition of neurological complications of HIV infection. METHODS: This
      retrospective study analyzed the clinical manifestations, laboratory and
      neuroimaging results of HIV-infected patients with neurological complications at
      Xuanwu hospital, Beijing, China from January 2011 to December 2014, one of top
      rated hospitals in Beijing, China. RESULTS: A diverse range of clinical diagnoses
      was identified, including encephalopathy, meningoencephalitis, peripheral
      neuropathy, multiple sclerosis, cerebral infarction and lymphoma associated with
      HIV infection. The mostly observed neurological disorders were motor/sensory
      deficits in the limbs (75%), cognitive impairments (42%) and fever (33%). Non
      specific results of laboratory tests, including elevated erythrocyte
      sedimentation rate (ESR), cerebrospinal fluid (CSF) protein concentration and
      IgG, were found. Brain Magnetic Resonance Imaging (MRI) abnormalities displayed a
      variety of patterns and distributions due to diverse clinical profiles.
      CONCLUSION: The clinical scenarios of HIV-infected patients are remarkably
      diverse and complex. Etiological tests would be cardinal to make more definitive
      diagnosis for HIV-infected patients. Prospective studies with follow-up were
      needed to bring more accurate information.

PMID- 29057860
TI  - Resting-State fMRI findings in patients with first-Episode idiopathic epilepsy
      before and after treatment.
AB  - OBJECTIVE: To detect resting-state functional MRI (rsfMRI) changes and their
      relationships with the clinical curative effect of anti-epileptic drugs (AEDs)
      for complex partial seizures (CPS) in epilepsy patients using the fractional
      amplitude of low frequency fluctuation (fALFF). METHODS: rfMRI data from 14 CPS
      patients enrolled between June 2015 and June 2016 in Department of Neurology,
      Affiliated Hospital of Inner Mongolia Medical University were retrospectively
      investigated and compared with findings from 14 healthy age-, gender-, handedness
      , and education-matched subjects. The patients were treated with first-line
      antiepileptic drugs for 12 weeks before undergoing a second rfMRI scan. fALFF
      data were processed using REST and SPM8 software. Whole-brain data were compared
      between the 2 groups. RESULTS: The abnormal findings in CPS patients
      significantly decreased or disappeared after AED treatment. CONCLUSION: Measuring
      fALFF is useful for identifying brain functional changes in patients with first
      episode epilepsy before and after treatment. Performing rfMRI is useful for
      evaluating treatment responses and may provide new insight into the
      pathophysiological mechanisms of epilepsy.

PMID- 29057861
TI  - Renal dysfunction as a predictor of acute stroke outcomes.
AB  - OBJECTIVE: To explore if renal dysfunction in terms of estimated glomerular
      filtration rate (eGFR) can be considered a risk factor for stroke outcomes.
      METHODS: The study population consisted of adults diagnosed with acute stroke
      admitted to the King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia
      between 2012 and 2015. Data was collected by chart review. The Modification of
      Diet in Renal Disease equation was used to estimate GFR. Patients were classified
      into 2 eGFR categories: eGFR more than 60 (normal) and eGFR less than or equal 60
      (low). RESULTS: A total of 727 patients were studied of whom 596 (82%) had normal
      eGFR and 131 (18%) had low eGFR. There were more males (68.5%). Ischemic strokes
      were more prevalent (87.2%). Urinary tract infections were more likely to occur
      in the low eGFR group (OR=2.047, 95% CI=1.024 - 4.093). They were also
      significantly more likely to die during admission (OR=3.772, 95% CI=1.609-8.844).
      There was a statistically significant degree of disability reflected by higher
      mRS (p=0.010) as well as higher post-stroke National Institute of Health Stroke
      Score scores in the low eGFR group (p=0.011). CONCLUSION: Estimated glomerular
      filtration rate is a possible predictor of stroke severity, disability and
      mortality.

PMID- 29057862
TI  - Neuroregression, coarse features, and oligosaccharides in urines.

PMID- 29057863
TI  - Publications pattern of clinical epilepsy research in Saudi Arabia.
AB  - OBJECTIVE: To assess the progress in the field clinical epilepsy in Saudi Arabia,
      by analyzing in depth the research output productivity and publication pattern,
      and to identify the current situation of epilepsy research and offer solutions.
      METHODS: Literature search strategy was designed to retrieve accessible articles
      that are related to epilepsy utilizing PubMed, Google Scholar, and Embase. The
      retrieved articles were analyzed with several parameters, then evaluated using
      Oxford Center of Evidence Based Medicine level of evidence scale. RESULTS: Of all
      identified articles, 90 were conducted in Kingdom of Saudi Arabia and therefore
      were included. The included articles had a frequency of only 3.5 publications per
      year, and growth of 24.4% between the periods of 1990-2003 and 2004-2016. Only
      13.3% of the articles were related to surgical epilepsy but the majority (86.7%)
      were related to medical epilepsy. Many articles (53.3%) were level III studies.
      The most common study design was retrospective studies in 35.6%, and the
      citations number ranged from 1-289 (Mean=7). CONCLUSION: Pattern of publications
      in clinical epilepsy researches revealed a slow growth rate in the frequency and
      a lower significance in the quality throughout the past 26 years. Active
      institutional and national promotion of clinical research is needed to help
      assess and therefore improve the quality of the provided epilepsy services.

PMID- 29057864
TI  - Fast methane diffusion at the interface of two clathrate structures.
AB  - Methane hydrates naturally form on Earth and in the interiors of some icy bodies
      of the Universe, and are also expected to play a paramount role in future energy
      and environmental technologies. Here we report experimental observation of an
      extremely fast methane diffusion at the interface of the two most common
      clathrate hydrate structures, namely clathrate structures I and II. Methane
      translational diffusion-measured by quasielastic neutron scattering at 0.8 GPa-is
      faster than that expected in pure supercritical methane at comparable pressure
      and temperature. This phenomenon could be an effect of strong confinement or of
      methane aggregation in the form of micro-nanobubbles at the interface of the two
      structures. Our results could have implications for understanding the replacement
      kinetics during sI-sII conversion in gas exchange experiments and for
      establishing the methane mobility in methane hydrates embedded in the cryosphere
      of large icy bodies in the Universe.

PMID- 29057865
TI  - Genetic rescue increases fitness and aids rapid recovery of an endangered
      marsupial population.
AB  - Genetic rescue has now been attempted in several threatened species, but the
      contribution of genetics per se to any increase in population health can be hard
      to identify. Rescue is expected to be particularly useful when individuals are
      introduced into small isolated populations with low levels of genetic variation.
      Here we consider such a situation by documenting genetic rescue in the mountain
      pygmy possum, Burramys parvus. Rapid population recovery occurred in the target
      population after the introduction of a small number of males from a large
      genetically diverged population. Initial hybrid fitness was more than two-fold
      higher than non-hybrids; hybrid animals had a larger body size, and female
      hybrids produced more pouch young and lived longer. Genetic rescue likely
      contributed to the largest population size ever being recorded at this site.
      These data point to genetic rescue as being a potentially useful option for the
      recovery of small threatened populations.

PMID- 29057867
TI  - Single-shot measurement of the orbital-angular-momentum spectrum of light.
AB  - The existing methods for measuring the orbital-angular-momentum (OAM) spectrum
      suffer from issues such as poor efficiency, strict interferometric stability
      requirements, and too much loss. Furthermore, most techniques inevitably discard
      part of the field and measure only a post-selected portion of the true spectrum.
      Here, we propose and demonstrate an interferometric technique for measuring the
      true OAM spectrum of optical fields in a single-shot manner. Our technique
      directly encodes the OAM-spectrum information in the azimuthal intensity profile
      of the output interferogram. In the absence of noise, the spectrum can be fully
      decoded using a single acquisition of the output interferogram, and, in the
      presence of noise, acquisition of two suitable interferograms is sufficient for
      the purpose. As an important application of our technique, we demonstrate
      measurements of the angular Schmidt spectrum of the entangled photons produced by
      parametric down-conversion and report a broad spectrum with the angular Schmidt
      number 82.1.

PMID- 29057866
TI  - Reconstitution of human shelterin complexes reveals unexpected stoichiometry and
      dual pathways to enhance telomerase processivity.
AB  - The human shelterin proteins associate with telomeric DNA to confer telomere
      protection and length regulation. They are thought to form higher-order protein
      complexes for their functions, but studies of shelterin proteins have been mostly
      limited to pairs of proteins. Here we co-express various human shelterin proteins
      and find that they form defined multi-subunit complexes. A complex harboring both
      TRF2 and POT1 has the strongest binding affinity to telomeric DNA substrates
      comprised of double-stranded DNA with a 3' single-stranded extension. TRF2
      interacts with TIN2 with an unexpected 2:1 stoichiometry in the context of
      shelterin (RAP12:TRF22:TIN21:TPP11:POT11). Tethering of TPP1 to the telomere
      either via TRF2-TIN2 or via POT1 gives equivalent enhancement of telomerase
      processivity. We also identify a peptide region from TPP1 that is both critical
      and sufficient for TIN2 interaction. Our findings reveal new information about
      the architecture of human shelterin and how it performs its functions at
      telomeres.

PMID- 29057868
TI  - Accessing the bottleneck in all-solid state batteries, lithium-ion transport over
      the solid-electrolyte-electrode interface.
AB  - Solid-state batteries potentially offer increased lithium-ion battery energy
      density and safety as required for large-scale production of electrical vehicles.
      One of the key challenges toward high-performance solid-state batteries is the
      large impedance posed by the electrode-electrolyte interface. However, direct
      assessment of the lithium-ion transport across realistic electrode-electrolyte
      interfaces is tedious. Here we report two-dimensional lithium-ion exchange NMR
      accessing the spontaneous lithium-ion transport, providing insight on the
      influence of electrode preparation and battery cycling on the lithium-ion
      transport over the interface between an argyrodite solid-electrolyte and a
      sulfide electrode. Interfacial conductivity is shown to depend strongly on the
      preparation method and demonstrated to drop dramatically after a few
      electrochemical (dis)charge cycles due to both losses in interfacial contact and
      increased diffusional barriers. The reported exchange NMR facilitates non
      invasive and selective measurement of lithium-ion interfacial transport,
      providing insight that can guide the electrolyte-electrode interface design for
      future all-solid-state batteries.

PMID- 29057869
TI  - Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1.
AB  - PERK signaling is required for cancer invasion and there is interest in targeting
      this pathway for therapy. Unfortunately, chemical inhibitors of PERK's kinase
      activity cause on-target side effects that have precluded their further
      development. One strategy for resolving this difficulty would be to target
      downstream components of the pathway that specifically mediate PERK's pro
      invasive and metastatic functions. Here we identify the transcription factor
      CREB3L1 as an essential mediator of PERK's pro-metastatic functions in breast
      cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype
      of triple-negative tumors, and its inhibition by genetic or pharmacological
      methods suppresses cancer cell invasion and metastasis. In patients with this
      tumor subtype, CREB3L1 expression is predictive of distant metastasis. These
      findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis
      and a druggable target for breast cancer therapy.

PMID- 29057870
TI  - Plasmonic tunnel junctions for single-molecule redox chemistry.
AB  - Nanoparticles attached just above a flat metallic surface can trap optical fields
      in the nanoscale gap. This enables local spectroscopy of a few molecules within
      each coupled plasmonic hotspot, with near thousand-fold enhancement of the
      incident fields. As a result of non-radiative relaxation pathways, the plasmons
      in such sub-nanometre cavities generate hot charge carriers, which can catalyse
      chemical reactions or induce redox processes in molecules located within the
      plasmonic hotspots. Here, surface-enhanced Raman spectroscopy allows us to track
      these hot-electron-induced chemical reduction processes in a series of different
      aromatic molecules. We demonstrate that by increasing the tunnelling barrier
      height and the dephasing strength, a transition from coherent to hopping electron
      transport occurs, enabling observation of redox processes in real time at the
      single-molecule level.

PMID- 29057871
TI  - Independent tuning of size and coverage of supported Pt nanoparticles using
      atomic layer deposition.
AB  - Synthetic methods that allow for the controlled design of well-defined Pt
      nanoparticles are highly desirable for fundamental catalysis research. In this
      work, we propose a strategy that allows precise and independent control of the Pt
      particle size and coverage. Our approach exploits the versatility of the atomic
      layer deposition (ALD) technique by combining two ALD processes for Pt using
      different reactants. The particle areal density is controlled by tailoring the
      number of ALD cycles using trimethyl(methylcyclopentadienyl)platinum and oxygen,
      while subsequent growth using the same Pt precursor in combination with nitrogen
      plasma allows for tuning of the particle size at the atomic level. The excellent
      control over the particle morphology is clearly demonstrated by means of in situ
      and ex situ X-ray fluorescence and grazing incidence small angle X-ray scattering
      experiments, providing information about the Pt loading, average particle
      dimensions, and mean center-to-center particle distance.

PMID- 29057872
TI  - Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered
      heart tissue.
AB  - Torsade de Pointes (TdP) is a lethal arrhythmia that is often drug-induced, thus
      there is an urgent need for development of models to test or predict the drug
      sensitivity of human cardiac tissue. Here, we present an in vitro TdP model using
      3D cardiac tissue sheets (CTSs) that contain a mixture of human induced
      pluripotent stem cell (hiPSC)-derived cardiomyocytes and non-myocytes. We
      simultaneously monitor the extracellular field potential (EFP) and the
      contractile movement of the CTSs. Upon treatment with IKr channel blockers, CTSs
      exhibit tachyarrhythmias with characteristics of TdP, including both a typical
      polymorphic EFP and meandering spiral wave re-entry. The TdP-like waveform is
      predominantly observed in CTSs with the cell mixture, indicating that cellular
      heterogeneity and the multi-layered 3D structure are both essential factors for
      reproducing TdP-like arrhythmias in vitro. This 3D model could provide the
      mechanistic detail underlying TdP generation and means for drug discovery and
      safety tests.

PMID- 29057873
TI  - Macrophage VLDLR mediates obesity-induced insulin resistance with adipose tissue
      inflammation.
AB  - Obesity is closely associated with increased adipose tissue macrophages (ATMs),
      which contribute to systemic insulin resistance and altered lipid metabolism by
      creating a pro-inflammatory environment. Very low-density lipoprotein receptor
      (VLDLR) is involved in lipoprotein uptake and storage. However, whether lipid
      uptake via VLDLR in macrophages affects obesity-induced inflammatory responses
      and insulin resistance is not well understood. Here we show that elevated VLDLR
      expression in ATMs promotes adipose tissue inflammation and glucose intolerance
      in obese mice. In macrophages, VLDL treatment upregulates intracellular levels of
      C16:0 ceramides in a VLDLR-dependent manner, which potentiates pro-inflammatory
      responses and promotes M1-like macrophage polarization. Adoptive transfer of
      VLDLR knockout bone marrow to wild-type mice relieves adipose tissue inflammation
      and improves insulin resistance in diet-induced obese mice. These findings
      suggest that increased VLDL-VLDLR signaling in ATMs aggravates adipose tissue
      inflammation and insulin resistance in obesity.

PMID- 29057874
TI  - Signatures of the topological s +- superconducting order parameter in the type-II
      Weyl semimetal T d-MoTe2.
AB  - In its orthorhombic T d polymorph, MoTe2 is a type-II Weyl semimetal, where the
      Weyl fermions emerge at the boundary between electron and hole pockets. Non
      saturating magnetoresistance and superconductivity were also observed in T d
      MoTe2. Understanding the superconductivity in T d-MoTe2, which was proposed to be
      topologically non-trivial, is of eminent interest. Here, we report high-pressure
      muon-spin rotation experiments probing the temperature-dependent magnetic
      penetration depth in T d-MoTe2. A substantial increase of the superfluid density
      and a linear scaling with the superconducting critical temperature T c is
      observed under pressure. Moreover, the superconducting order parameter in T d
      MoTe2 is determined to have 2-gap s-wave symmetry. We also exclude time-reversal
      symmetry breaking in the superconducting state with zero-field MUSR experiments.
      Considering the strong suppression of T c in MoTe2 by disorder, we suggest that
      topologically non-trivial s +- state is more likely to be realized in MoTe2 than
      the topologically trivial s ++ state.

PMID- 29057875
TI  - Organic coating on biochar explains its nutrient retention and stimulation of
      soil fertility.
AB  - Amending soil with biochar (pyrolized biomass) is suggested as a globally
      applicable approach to address climate change and soil degradation by carbon
      sequestration, reducing soil-borne greenhouse-gas emissions and increasing soil
      nutrient retention. Biochar was shown to promote plant growth, especially when
      combined with nutrient-rich organic matter, e.g., co-composted biochar. Plant
      growth promotion was explained by slow release of nutrients, although a
      mechanistic understanding of nutrient storage in biochar is missing. Here we
      identify a complex, nutrient-rich organic coating on co-composted biochar that
      covers the outer and inner (pore) surfaces of biochar particles using high
      resolution spectro(micro)scopy and mass spectrometry. Fast field cycling nuclear
      magnetic resonance, electrochemical analysis and gas adsorption demonstrated that
      this coating adds hydrophilicity, redox-active moieties, and additional
      mesoporosity, which strengthens biochar-water interactions and thus enhances
      nutrient retention. This implies that the functioning of biochar in soil is
      determined by the formation of an organic coating, rather than biochar surface
      oxidation, as previously suggested.

PMID- 29057876
TI  - Comprehensive analysis of normal adjacent to tumor transcriptomes.
AB  - Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a
      control in cancer studies. However, little is known about the transcriptomic
      profile of NAT, how it is influenced by the tumor, and how the profile compares
      with non-tumor-bearing tissues. Here, we integrate data from the Genotype-Tissue
      Expression project and The Cancer Genome Atlas to comprehensively analyze the
      transcriptomes of healthy, NAT, and tumor tissues in 6506 samples across eight
      tissues and corresponding tumor types. Our analysis shows that NAT presents a
      unique intermediate state between healthy and tumor. Differential gene expression
      and protein-protein interaction analyses reveal altered pathways shared among
      NATs across tissue types. We characterize a set of 18 genes that are specifically
      activated in NATs. By applying pathway and tissue composition analyses, we
      suggest a pan-cancer mechanism of pro-inflammatory signals from the tumor
      stimulates an inflammatory response in the adjacent endothelium.

PMID- 29057877
TI  - Large-scale water collection of bioinspired cavity-microfibers.
AB  - Large-scale and high-efficient water collection of microfibers with long-term
      durability still remains challenging. Here we present well-controlled,
      bioinspired spindle-knot microfibers with cavity knots (named cavity-microfiber),
      precisely fabricated via a simple gas-in-water microfluidic method, to address
      this challenge. The cavity-microfiber is endowed with unique surface roughness,
      mechanical strength, and long-term durability due to the design of cavity as well
      as polymer composition, thus enabling an outstanding performance of water
      collection. The maximum water volume collected on a single knot is almost 495
      times than that of the knot on the cavity-microfiber. Moreover, the spider-web
      like networks assembled controllably by cavity-microfibers demonstrate excellent
      large-scale and high-efficient water collection. To maximize the water-collecting
      capacity, nodes/intersections should be designed on the topology of the network
      as many as possible. Our light-weighted yet tough, low-cost microfibers with high
      efficiency in directional water transportation offers promising opportunities for
      large-scale water collection in water-deficient areas.

PMID- 29057878
TI  - The impact of anthropogenic land use and land cover change on regional climate
      extremes.
AB  - Land surface processes modulate the severity of heat waves, droughts, and other
      extreme events. However, models show contrasting effects of land surface changes
      on extreme temperatures. Here, we use an earth system model from the Geophysical
      Fluid Dynamics Laboratory to investigate regional impacts of land use and land
      cover change on combined extremes of temperature and humidity, namely aridity and
      moist enthalpy, quantities central to human physiological experience of near
      surface climate. The model's near-surface temperature response to deforestation
      is consistent with recent observations, and conversion of mid-latitude natural
      forests to cropland and pastures is accompanied by an increase in the occurrence
      of hot-dry summers from once-in-a-decade to every 2-3 years. In the tropics, long
      time-scale oceanic variability precludes determination of how much of a small,
      but significant, increase in moist enthalpy throughout the year stems from the
      model's novel representation of historical patterns of wood harvesting, shifting
      cultivation, and regrowth of secondary vegetation and how much is forced by
      internal variability within the tropical oceans.

PMID- 29057880
TI  - Continuous-variable geometric phase and its manipulation for quantum computation
      in a superconducting circuit.
AB  - Geometric phase, associated with holonomy transformation in quantum state space,
      is an important quantum-mechanical effect. Besides fundamental interest, this
      effect has practical applications, among which geometric quantum computation is a
      paradigm, where quantum logic operations are realized through geometric phase
      manipulation that has some intrinsic noise-resilient advantages and may enable
      simplified implementation of multi-qubit gates compared to the dynamical
      approach. Here we report observation of a continuous-variable geometric phase and
      demonstrate a quantum gate protocol based on this phase in a superconducting
      circuit, where five qubits are controllably coupled to a resonator. Our geometric
      approach allows for one-step implementation of n-qubit controlled-phase gates,
      which represents a remarkable advantage compared to gate decomposition methods,
      where the number of required steps dramatically increases with n. Following this
      approach, we realize these gates with n up to 4, verifying the high efficiency of
      this geometric manipulation for quantum computation.

PMID- 29057879
TI  - Deletion of 3p13-14 locus spanning FOXP1 to SHQ1 cooperates with PTEN loss in
      prostate oncogenesis.
AB  - A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in
      prostate cancer and lost broadly in a range of cancers but has unknown
      significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1
      deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that
      loss of component genes correlates with prostate, breast, and head and neck
      cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate
      tumorigenesis in mice in combination with Pten loss, consistent with the
      association of FOXP1-SHQ1 and PTEN loss observed in human cancers. Tumors with
      combined Foxp1-Shq1 and Pten deletion show increased proliferation and anaplastic
      dedifferentiation, as well as mTORC1 hyperactivation with reduced Akt
      phosphorylation. Foxp1-Shq1 deletion restores expression of AR target genes
      repressed in tumors with Pten loss, circumventing PI3K-mediated repression of the
      androgen axis. Moreover, FOXP1-SHQ1 deletion has prognostic relevance, with
      cancer recurrence associated with combined loss of PTEN and FOXP1-SHQ1 genes.

PMID- 29057881
TI  - Ultrasound localization microscopy to image and assess microvasculature in a rat
      kidney.
AB  - The recent development of ultrasound localization microscopy, where individual
      microbubbles (contrast agents) are detected and tracked within the vasculature,
      provides new opportunities for imaging the vasculature of entire organs with a
      spatial resolution below the diffraction limit. In stationary tissue, recent
      studies have demonstrated a theoretical resolution on the order of microns. In
      this work, single microbubbles were localized in vivo in a rat kidney using a
      dedicated high frame rate imaging sequence. Organ motion was tracked by assuming
      rigid motion (translation and rotation) and appropriate correction was applied.
      In contrast to previous work, coherence-based non-linear phase inversion
      processing was used to reject tissue echoes while maintaining echoes from very
      slowly moving microbubbles. Blood velocity in the small vessels was estimated by
      tracking microbubbles, demonstrating the potential of this technique to improve
      vascular characterization. Previous optical studies of microbubbles in vessels of
      approximately 20 microns have shown that expansion is constrained, suggesting
      that microbubble echoes would be difficult to detect in such regions. We
      therefore utilized the echoes from individual MBs as microscopic sensors of slow
      flow associated with such vessels and demonstrate that highly correlated,
      wideband echoes are detected from individual microbubbles in vessels with flow
      rates below 2 mm/s.

PMID- 29057882
TI  - Manipulation of photoassociation of ultracold Cs atoms with tunable scattering
      length by external magnetic fields.
AB  - We demonstrate that for ultracold, optically trapped Cs atoms the
      photoassociation (PA) can be manipulated by using external uniform magnetic
      fields due to the alteration of the scattering wavefunction in the region of the
      free-bound optical transition. We present PA-induced atom loss measurements with
      the same intensity for PA laser but different external magnetic fields, and
      analyze main contributions of the PA to the variation of the number of atoms in
      the trap. The PA rate exhibits a strong dependence on the changing uniform
      magnetic field. The experimental data are simulated within the model of a single
      channel one-well rectangular potential, whose depth is adjusted so as to assure
      the predicted variation of the scattering length with the magnetic field. The
      computational and experimental results are in a reasonable agreement to each
      other. The same model is used to illustrate some general properties of the two
      body quantum system in the near-threshold state.

PMID- 29057883
TI  - Non-muscular myosin light chain kinase triggers intermittent hypoxia-induced
      interleukin-6 release, endothelial dysfunction and permeability.
AB  - Obstructive sleep apnea is characterized by intermittent hypoxia (IH) which
      alters endothelial function, induces inflammation and accelerates atherosclerosis
      induced cardiovascular diseases. The non-muscular myosin light chain kinase
      (nmMLCK) isoform contributes to endothelial cell-cell junction opening. Deletion
      of nmMLCK protects mice from death in septic shock models and prevents
      atherosclerosis in high-fat diet-fed mice. The aim of the study was to analyze
      the implication of nmMLCK in IH-induced vascular inflammation. Human aortic
      endothelial cells were exposed to 6 hours of IH in absence or presence of nmMLCK
      inhibitors, ML-7 (5 uM) or PIK (150 uM). IH increased reactive oxygen species
      (ROS) and nitric oxide (NO) production, p65-NFkappaB activation and IL-6
      secretion. While nmMLCK inhibition did not prevent IH-induced ROS production and
      p65-NFkappaB activation, it decreased NO production and partially prevented IL-6
      secretion. IH-induced IL-6 secretion and vesicle-associated membrane protein
      associated vesicles re-organization were inhibited in presence of the inhibitor
      of protein secretion, brefeldin A, or ML-7. IH increased monocytes
      transendothelial migration that was partially prevented by ML-7. Finally, IH
      reduced endothelium-dependent relaxation to acetylcholine of aortas from wild
      type but not those taken from nmMLCK-deficient mice. These results suggest that
      nmMLCK participates to IH-induced endothelial dysfunction resulting from
      cytokines secretion and endothelial permeability.

PMID- 29057884
TI  - Dynamics of the stochastic chemostat with Monod-Haldane response function.
AB  - The stochastic chemostat model with Monod-Haldane response function is perturbed
      by environmental white noise. This model has a global positive solution. We
      demonstrate that there is a stationary distribution of the stochastic model and
      the system is ergodic under appropriate conditions, on the basis of Khasminskii's
      theory on ergodicity. Sufficient criteria for extinction of the microbial
      population in the stochastic system are established. These conditions depend
      strongly on the Brownian motion. We find that even small scale white noise can
      promote the survival of microorganism populations, while large scale noise can
      lead to extinction. Numerical simulations are carried out to illustrate our
      theoretical results.

PMID- 29057885
TI  - Acoustic emission multiplets as early warnings of fatigue failure in metallic
      materials.
AB  - Fatigue, i.e. the failure of mechanical structures under cycling loading, remains
      a considerable technological challenge as it occurs unexpectedly when the
      structure is operating apparently in a safe and steady state regime, without
      external signs of mechanical deterioration. Here we report for the first time, in
      different metallic materials, the detection of acoustic emissions specific of
      fatigue crack growth. These so-called acoustic multiplets are characterized by
      nearly identical waveforms, signature of a unique source, are repeatedly
      triggered over many successive loading cycles at the same stress level, and
      originate from a single location. They mark the slow, incremental propagation of
      a fatigue crack at each cycle, or the rubbing along its faces. Being specific to
      fatigue cracking, they can be used as early warnings of crack propagation, which
      will ultimately lead to structural failure. Their detection and characterization
      thus open the way towards a new, reliable monitoring of the onset of fatigue
      cracking during mechanical tests or within structures in service.

PMID- 29057886
TI  - Semi-Empirical Estimation of Dean Flow Velocity in Curved Microchannels.
AB  - Curved and spiral microfluidic channels are widely used in particle and cell
      sorting applications. However, the average Dean velocity of secondary vortices
      which is an important design parameter in these devices cannot be estimated
      precisely with the current knowledge in the field. In this paper, we used co
      flows of dyed liquids in curved microchannels with different radii of curvatures
      and monitored the lateral displacement of fluids using optical microscopy. A
      quantitative Switching Index parameter was then introduced to calculate the
      average Dean velocity in these channels. Additionally, we developed a validated
      numerical model to expand our investigations to elucidating the effects of
      channel hydraulic diameter, width, and height as well as fluid kinematic
      viscosity on Dean velocity. Accordingly, a non-dimensional comprehensive
      correlation was developed based on our numerical model and validated against
      experimental results. The proposed correlation can be used extensively for the
      design of curved microchannels for manipulation of fluids, particles, and
      biological substances in spiral microfluidic devices.

PMID- 29057887
TI  - Antimicrobial Peptides Secreted From Human Cryopreserved Viable Amniotic Membrane
      Contribute to its Antibacterial Activity.
AB  - Chronic wounds remain a large problem in the field of medicine and are often
      associated with risk of infection and amputation. Recently, a commercially
      available human cryopreserved viable amniotic membrane (hCVAM) has been shown to
      effectively promote wound closure and reduce wound-related infections. A
      sprevious study indicates that hCVAM can inhibit the growth of bacteria
      associated with chronic wounds. In the present study, we investigated the
      mechanism of hCVAM antimicrobial activity. Our data demonstrate that
      antimicrobial activities against common pathogens in chronic wounds such as
      P.aeruginosa, S.aureus and Methicillin-resistant S.aureus (MRSA) are mediated via
      the secretion of soluble factors by viable cells in hCVAM and that these factors
      are proteins in nature. Further, we show that genes for antimicrobial peptides
      (AMPs) including human beta-defensins (HBDs) are expressed by hCVAM and that
      expression levels positively correlate with antimicrobial activity of hCVAM. At
      the protein level, our data indicate that HBD2 and HBD3 are secreted by hCVAM and
      directly contribute to its activity against P. aeruginosa. These data provide
      evidence that soluble factors including AMPs are hCVAM antimicrobial agents and
      are consistent with a role for AMPs in mediating antimicrobial properties of the
      membrane.

PMID- 29057888
TI  - Multitwist Mobius Strips and Twisted Ribbons in the Polarization of Paraxial
      Light Beams.
AB  - The polarization of light can exhibit unusual features when singular optical
      beams are involved. In 3-dimensional polarized random media the polarization
      orientation around singularities describe 1/2 or 3/2 Mobius strips. It has been
      predicted that if singular beams intersect non-collinearly in free space, the
      polarization ellipse rotates forming many-turn Mobius strips or twisted ribbons
      along closed loops around a central singularity. These polarization features are
      important because polarization is an aspect of light that mediate strong
      interactions with matter, with potential for new applications. We examined the
      non-collinear superposition of two unfocused paraxial light beams when one of
      them carried an optical vortex and the other one a uniform phase front, both in
      orthogonal states of circular polarization. It is known that these superpositions
      in 2-dimensions produce space-variant patterns of polarization. Relying on the
      symmetry of the problem, we extracted the 3-dimensional patterns from projective
      measurements, and confirmed the formation of many-turn Mobius strips or twisted
      ribbons when the topological charge of one of the component beams was odd or
      even, respectively. The measurements agree well with the modelings and confirmed
      that these types of patterns occur at macroscopic length scales and in ordinary
      superposition situations.

PMID- 29057889
TI  - Racial disparities in patient survival and tumor mutation burden, and the
      association between tumor mutation burden and cancer incidence rate.
AB  - The causes underlying racial disparities in cancer are multifactorial. In
      addition to socioeconomic issues, biological factors may contribute to these
      inequities, especially in disease incidence and patient survival. To date, there
      have been few studies that relate the disparities in these aspects to genetic
      aberrations. In this work, we studied the impacts of race on the patient survival
      and tumor mutation burden using the data released by the Cancer Genome Atlas
      (TCGA). The potential relationship between mutation burden and disease incidence
      is further inferred by an integrative analysis of TCGA data and the data from the
      Surveillance, Epidemiology, and End Results (SEER) Program. The results show that
      disparities are present (p < 0.05) in patient survival of five cancers, such as
      head and neck squamous cell carcinoma. The numbers of tumor driver mutations are
      differentiated (p < 0.05) over the racial groups in five cancers, such as lung
      adenocarcinoma. By treating a specific cancer type and a racial group as an
      "experimental unit", driver mutation numbers demonstrate a significant (r = 0.46,
      p < 0.002) positive correlation with cancer incidence rates, especially when the
      five cancers with mutational disparities are exclusively focused (r = 0.88, p <
      0.00002). These results enrich our understanding of racial disparities in cancer
      and carcinogenic process.

PMID- 29057890
TI  - Effect of Nitrate Leaching Caused by Swine Manure Application in Fields of the
      Yellow River Irrigation Zone of Ningxia, China.
AB  - A five-year swine manure application trial and a study of nitrate leaching losses
      have been conducted. There were three treatments: traditional without manure
      (CK), traditional matched manure 4500 kg ha-2 (T1) and traditional matched manure
      9000 kg ha-2 (T2). Nitrate nitrogen leaching losses at the 30-, 60-, and 90-cm
      soil layers were measured using the resin core method. The results indicate that
      the swine manure application did not noticeably increase soil nitrate leaching
      losses in the 30-cm layer. T1 (16.85 +/- 0.40 kg ha-2) and T2 (17.01  degrees
      C0.46 kg ha-2) were not significantly different than CK (15.96 +/- 0.41 kg ha-2)
      (P < 0.05), which was also the case at the 60-cm layer. However, there are
      significant differences between the treatments and CK at the 90-cm layer,
      although there were no significant differences between T1 and T2 in that layer.
      The application of manure can increase soil organic matter (SOM) and total
      nitrogen (TN). The SOM of T1 and T2 were increased to 0.95 g kg-1 and 1.41 g kg
      1, respectively. The TN values of CK, T1 and T2 were 0.72, 0.78 and 0.88 g kg-1,
      respectively, in the 0 to 30 cm layer, and were improved by 7.72% and 22.04%.

PMID- 29057891
TI  - Exhaustive search for epistatic effects on the human methylome.
AB  - Studies assessing the existence and magnitude of epistatic effects on complex
      human traits provide inconclusive results. The study of such effects is
      complicated by considerable increase in computational burden, model complexity,
      and model uncertainty, which in concert decrease model stability. An additional
      source introducing significant uncertainty with regard to the detection of robust
      epistasis is the biological distance between the genetic variation and the trait
      under study. Here we studied CpG methylation, a genetically complex molecular
      trait that is particularly close to genomic variation, and performed an
      exhaustive search for two-locus epistatic effects on the CpG-methylation signal
      in two cohorts of healthy young subjects. We detected robust epistatic effects
      for a small number of CpGs (N = 404). Our results indicate that epistatic effects
      explain only a minor part of variation in DNA-CpG methylation. Interestingly,
      these CpGs were more likely to be associated with gene-expression of nearby
      genes, as also shown by their overrepresentation in DNase I hypersensitivity
      sites and underrepresentation in CpG islands. Finally, gene ontology analysis
      showed a significant enrichment of these CpGs in pathways related to HPV
      infection and cancer.

PMID- 29057892
TI  - Structural and Photophysical Properties of Methylammonium Lead Tribromide
      (MAPbBr3) Single Crystals.
AB  - The structural and photophysical characteristics of MAPbBr3 single crystals
      prepared using the inverse temperature crystallization method are evaluated using
      temperature-dependent X-ray diffraction (XRD) and optical spectroscopy. Contrary
      to previous research reports on perovskite materials, we study phase transitions
      in crystal lattice structures accompanied with changes in optical properties
      expand throughout a wide temperature range of 300-1.5 K. The XRD studies reveal
      several phase transitions occurred at ~210 K, ~145 K, and ~80 K, respectively.
      The coexistence of two different crystallographic phases was observed at a
      temperature below 145 K. The emission peaks in the PL spectra are all asymmetric
      in line shape with weak and broad shoulders near the absorption edges, which are
      attributed to the Br atom vacancy on the surface of the crystals. The time
      resolved PL measurements reveal the effect of the desorption/adsorption of gas
      molecules on the crystal surface on the PL lifetimes. Raman spectroscopy results
      indicate the strong interplays between cations and different halide atoms.
      Lastly, no diamagnetic shift or split in emission peaks can be observed in the
      magneto-PL spectra even at an applied magnetic field up to 5 T and at a
      temperature as low as 1.5 K.

PMID- 29057894
TI  - Open-Cavity Spun Fiber Raman Lasers with Dual Polarization Output.
AB  - Random distributed feedback fiber Raman lasers, where the feedback mechanism is
      provided by Rayleigh backscattering, have attracted a good deal of attention
      since they were first introduced in 2010. Their simple and flexible design,
      combined with good lasing efficiency and beam quality properties, comparable to
      those of standard cavity lasers, have led to multiple applications, particularly
      in the fields of fiber sensing and optical communications. In spite of these
      advances, the polarization properties of random fiber Raman lasers, which can
      strongly affect their performance in both sensing and communications, have barely
      been explored so far. In this article we experimentally and theoretically study
      the polarization properties of different open-cavity laser designs, based on
      either standard transmission fibers or low polarization-mode-dispersion spun
      fibers. By using high-power, highly-polarized pumps, we demonstrate controllable
      polarization-pulling and simultaneous lasing at close wavelengths with different
      output polarization properties in random distributed feedback fiber Raman lasers.
      These results advance our understanding of the polarization dynamics in ultralong
      lasers, and pave the way to the design of novel fiber laser sources capable of
      polarization-sensitive sensing and distributed amplification.

PMID- 29057893
TI  - R/G editing in GluA2Rflop modulates the functional difference between GluA1 flip
      and flop variants in GluA1/2R heteromeric channels.
AB  - In alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors, RNA
      editing and alternative splicing generate sequence variants, and those variants,
      as in GluA2-4 AMPA receptor subunits, generally show different properties. Yet,
      earlier studies have shown that the alternatively spliced, flip and flop variants
      of GluA1 AMPA receptor subunit exhibit no functional difference in homomeric
      channel form. Using a laser-pulse photolysis technique, combined with whole-cell
      recording, we measured the rate of channel opening, among other kinetic
      properties, for a series of AMPA channels with different arginine/glycine (R/G)
      editing and flip/flop status. We find that R/G editing in the GluA2 subunit
      modulates the channel properties in both homomeric (GluA2Q) and complex
      (GluA2Q/2R and GluA1/2R) channel forms. However, R/G editing is only effective in
      flop channels. Specifically, editing at the R/G site on the GluA2R flop isoform
      accelerates the rate of channel opening and desensitization for GluA1/2R channels
      more pronouncedly with the GluA1 being in the flop form than in the flip form;
      yet R/G editing has no effect on either channel-closing rate or EC50. Our results
      suggest R/G editing via GluA2R serve as a regulatory mechanism to modulate the
      function of GluA2R-containing, native receptors involved in fast excitatory
      synaptic transmission.

PMID- 29057895
TI  - Cholinergic Stimulation Improves Oxidative Stress and Inflammation in
      Experimental Myocardial Infarction.
AB  - We previously reported that cholinergic stimulation with pyridostigmine (PY)
      induces anti-inflammatory cell recruitment soon after myocardial infarction (MI).
      In this study, we evaluated the anti-inflammatory effects of PY during the
      proliferative phase of cardiac repair by analyzing the infiltration of
      macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines.
      Wistar rats underwent control sham surgery or ligation of the left coronary
      artery and were randomly allocated to remain untreated (untreated infarcted
      group, I) or to receive PY (30 mg.kg(-1).day(-1)) in the supplied water
      (infarcted treated group, I + PY). Blood pressure and heart rate variability were
      registered at day 5 post-MI. The animals were euthanized 7 days after
      thoracotomy, when the hearts were removed and processed for immunohistochemistry
      (CD68, CD206, FOXP3), cytokines (IL-1beta, IL-6, IL-10, TNF-alpha) and oxidative
      stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and
      protein peroxidation). PY treatment increased parasympathetic modulation, M2
      macrophages and the anti-oxidant enzyme activity but reduced protein oxidation
      (carbonyls) and the concentration of IL-1beta, IL-6, TNF-alpha and IL-10.
      Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti
      inflammatory cell enrollment as well as prevents oxidative stress and cytokine
      production after MI.

PMID- 29057896
TI  - Interactions between seagrasses and seaweeds during surge nitrogen acquisition
      determine interspecific competition.
AB  - Seagrasses dominate shallow coastal environments where nitrogen (N) availability
      in the water column is often sporadic and mainly in the form of pulses. We
      investigated the N uptake competition between seagrasses and seaweeds through a
      series of 15N surge uptake experiments combining single-species and mixed
      incubations across ammonium concentrations. N surge uptake rates of seagrasses
      were 2 to 14-fold higher than those of seaweeds in the majority of combinations,
      showing that seagrasses are generally in a competitive advantage over seaweeds in
      N-poor environments with N-pulses. No threshold concentration of ammonium was
      found beyond which seaweeds performed better than seagrasses. Mixed incubations
      revealed interspecific interactions that affected rates positively and
      negatively. Uptake rates obtained in single-species incubations, therefore,
      cannot always be used to predict the outcome of uptake competition. Only two
      (Zostera marina vs. Ulva rotundata and Zostera marina vs. Codium decorticatum) of
      the nine combinations tested (Z. marina, Z. noltei and Cymodocea nodosa vs. U.
      rotundata, C. decorticatum and Dictyota dichotoma) were found to enhance
      macroalgal uptake. Our results showed that the surge uptake capacity of
      seagrasses represents an important mechanism in their N acquisition strategy that
      justifies their dominance in shallow oligotrophic environments.

PMID- 29057897
TI  - Alcohol consumption impairs the ependymal cilia motility in the brain ventricles.
AB  - Ependymal cilia protrude into the central canal of the brain ventricles and
      spinal cord to circulate the cerebral spinal fluid (CSF). Ependymal cilia
      dysfunction can hinder the movement of CSF leading to an abnormal accumulation of
      CSF within the brain known as hydrocephalus. Although the etiology of
      hydrocephalus was studied before, the effects of ethanol ingestion on ependymal
      cilia function have not been investigated in vivo. Here, we report three distinct
      types of ependymal cilia, type-I, type-II and type-III classified based upon
      their beating frequency, their beating angle, and their distinct localization
      within the mouse brain-lateral ventricle. Our studies show for the first time
      that oral gavage of ethanol decreased the beating frequency of all three types of
      ependymal cilia in both the third and the lateral rat brain ventricles in vivo.
      Furthermore, we show for the first time that hydin, a hydrocephalus-inducing gene
      product whose mutation impairs ciliary motility, and polycystin-2, whose ablation
      is associated with hydrocephalus are colocalized to the ependymal cilia. Thus,
      our studies reinforce the presence of three types of ependymal cilia in the brain
      ventricles and demonstrate the involvement of ethanol as a risk factor for the
      impairment of ependymal cilia motility in the brain.

PMID- 29057898
TI  - Spatiotemporal Variability in Phosphorus Species in the Pearl River Estuary:
      Influence of the River Discharge.
AB  - Phosphorus was the stoichiometrically limiting nutrient in the Pearl River
      Estuary (PRE). In order to examine how the river discharge regulates phosphorus
      dynamics in the PRE, the concentrations of dissolved inorganic phosphorus (DIP)
      and organic phosphorus (DOP), particulate inorganic phosphorus (PIP) and organic
      phosphorus (POP) in the water column were determined in May 2015 (spring), August
      2015 (summer) and January 2016 (winter). Our results showed that all types of
      phosphorus were significantly lower in spring and summer than in winter. The
      Pearl River discharge input played an important role in regulating phosphorus
      dynamics. Strong vertical mixing in winter resulted in high levels of total
      particulate phosphorus (1.50 +/- 0.97 MUM) and dissolved phosphate (DIP: 1.44 +/-
      0.57 MUM, DOP: 0.58 +/- 0.42 MUM) at the surface. On the other hand, the river
      discharge input created stratification in spring and summer, favoring the
      settlement of suspended particulate matter and enhancing light levels. This
      promoted phytoplankton growth, which was responsible for a DIP drawdown of 0.43
      +/- 0.37 MUM in May and 0.56 +/- 0.42 MUM in August at the surface. Additionally,
      stratification restricted the bottom phosphorus replenishment. Our findings
      provided an insight into processes causing stoichiometric P limitation in the
      PRE.

PMID- 29057899
TI  - Breast-Lesion Characterization using Textural Features of Quantitative Ultrasound
      Parametric Maps.
AB  - This study evaluated, for the first time, the efficacy of quantitative ultrasound
      (QUS) spectral parametric maps in conjunction with texture-analysis techniques to
      differentiate non-invasively benign versus malignant breast lesions. Ultrasound B
      mode images and radiofrequency data were acquired from 78 patients with
      suspicious breast lesions. QUS spectral-analysis techniques were performed on
      radiofrequency data to generate parametric maps of mid-band fit, spectral slope,
      spectral intercept, spacing among scatterers, average scatterer diameter, and
      average acoustic concentration. Texture-analysis techniques were applied to
      determine imaging biomarkers consisting of mean, contrast, correlation, energy
      and homogeneity features of parametric maps. These biomarkers were utilized to
      classify benign versus malignant lesions with leave-one-patient-out cross
      validation. Results were compared to histopathology findings from biopsy
      specimens and radiology reports on MR images to evaluate the accuracy of
      technique. Among the biomarkers investigated, one mean-value parameter and 14
      textural features demonstrated statistically significant differences (p < 0.05)
      between the two lesion types. A hybrid biomarker developed using a stepwise
      feature selection method could classify the legions with a sensitivity of 96%, a
      specificity of 84%, and an AUC of 0.97. Findings from this study pave the way
      towards adapting novel QUS-based frameworks for breast cancer screening and rapid
      diagnosis in clinic.

PMID- 29057900
TI  - Mitochondrial genomes of the key zooplankton copepods Arctic Calanus glacialis
      and North Atlantic Calanus finmarchicus with the longest crustacean non-coding
      regions.
AB  - We determined the nearly complete mitochondrial genomes of the Arctic Calanus
      glacialis and its North Atlantic sibling Calanus finmarchicus, which are key
      zooplankton components in marine ecosystems. The sequenced part of C. glacialis
      mitogenome is 27,342 bp long and consists of two contigs, while for C.
      finmarchicus it is 29,462 bp and six contigs, what makes them the longest
      reported copepod mitogenomes. The typical set of metazoan mitochondrial genes is
      present in these mitogenomes, although the non-coding regions (NCRs) are
      unusually long and complex. The mitogenomes of the closest species C. glacialis
      and C. finmarchicus, followed by the North Pacific C. sinicus, are structurally
      similar and differ from the much more typical of deep-water, Arctic C.
      hyperboreus. This evolutionary trend for the expansion of NCRs within the Calanus
      mitogenomes increases mitochondrial DNA density, what resulted in its similar
      density to the nuclear genome. Given large differences in the length and
      structure of C. glacialis and C. finmarchicus mitogenomes, we conclude that the
      species are genetically distinct and thus cannot hybridize. The molecular
      resources presented here: the mitogenomic and rDNA sequences, and the database of
      repetitive elements should facilitate the development of genetic markers suitable
      in pursuing evolutionary research in copepods.

PMID- 29057901
TI  - Multi-modal sexual displays in Australian humpback dolphins.
AB  - Sexual displays enriched by object carrying serve to increase individual male
      fitness, yet are uncommon phenomena in the animal kingdom. While they have been
      documented in a variety of taxa, primarily birds, they are rare outside non-human
      mammals. Here, we document marine sponge presenting associated with visual and
      acoustic posturing found in several, geographically widespread populations of
      Australian humpback dolphins (Sousa sahulensis) over ten years of observation.
      Only adult males presented marine sponges, typically doing so in the presence of
      sexually mature females, although social groups predominantly consisted of mixed
      age and sex classes. Male humpback dolphins appear to be using sponges for
      signalling purposes in multi-modal sexual displays. Further, based on limited
      behavioural and genetic data, we hypothesise that pairs of adult male Sousa form
      at least temporary coalitions or alliances. The use of objects in sexual displays
      by non-human mammals is rare and, moreover, cooperation between males in the
      pursuit of an indivisible resource is an evolutionary hurdle relatively few
      species have overcome. These findings suggest a hitherto unrecognised level of
      social complexity in humpback dolphins.

PMID- 29057903
TI  - An optical Fourier transform coprocessor with direct phase determination.
AB  - The Fourier transform is a ubiquitous mathematical operation which arises
      naturally in optics. We propose and demonstrate a practical method to optically
      evaluate a complex-to-complex discrete Fourier transform. By implementing the
      Fourier transform optically we can overcome the limiting O(nlogn) complexity of
      fast Fourier transform algorithms. Efficiently extracting the phase from the well
      known optical Fourier transform is challenging. By appropriately decomposing the
      input and exploiting symmetries of the Fourier transform we are able to determine
      the phase directly from straightforward intensity measurements, creating an
      optical Fourier transform with O(n) apparent complexity. Performing larger
      optical Fourier transforms requires higher resolution spatial light modulators,
      but the execution time remains unchanged. This method could unlock the potential
      of the optical Fourier transform to permit 2D complex-to-complex discrete Fourier
      transforms with a performance that is currently untenable, with applications
      across information processing and computational physics.

PMID- 29057902
TI  - TRPV4 activation triggers protective responses to bacterial lipopolysaccharides
      in airway epithelial cells.
AB  - Lipopolysaccharides (LPS), the major components of the wall of gram-negative
      bacteria, trigger powerful defensive responses in the airways via mechanisms
      thought to rely solely on the Toll-like receptor 4 (TLR4) immune pathway. Here we
      show that airway epithelial cells display an increase in intracellular Ca2+
      concentration within seconds of LPS application. This response occurs in a TLR4
      independent manner, via activation of the transient receptor potential vanilloid
      4 cation channel (TRPV4). We found that TRPV4 mediates immediate LPS-induced
      increases in ciliary beat frequency and the production of bactericidal nitric
      oxide. Upon LPS challenge TRPV4-deficient mice display exacerbated ventilatory
      changes and recruitment of polymorphonuclear leukocytes into the airways. We
      conclude that LPS-induced activation of TRPV4 triggers signaling mechanisms that
      operate faster and independently from the canonical TLR4 immune pathway, leading
      to immediate protective responses such as direct antimicrobial action, increase
      in airway clearance, and the regulation of the inflammatory innate immune
      reaction.

PMID- 29057904
TI  - The ANK repeats of Notch-4/Int3 activate NF-kappaB canonical pathway in the
      absence of Rbpj and causes mammary tumorigenesis.
AB  - Transgenic mice expressing the Notch-4 intracellular domain (designated Int3) in
      the mammary gland have two phenotypes exhibited with 100% penetrance: arrest of
      mammary alveolar/lobular development and mammary tumorigenesis. Notch-4 signaling
      is mediated primarily through the interaction of Int3 with the transcription
      repressor/activator Rbpj. Interestingly, WAP-Int3/Rbpj knockout mice have normal
      mammary gland development but still developed mammary tumors with a slightly
      longer latency than the WAP-Int3 mice. Thus, Notch-induced mammary tumor
      development is Rbpj-independent. Here, we show that Int3 activates NF-kappaB in
      HC11 cells in absence of Rbpj through an association with the IKK signalosome.
      Int3 induced the canonical NF-kappaB activity and P50 phosphorylation in HC11
      cells without altering the NF-kappaB2 pathway. The minimal domain within the Int3
      protein required to activate NF-kappaB consists of the CDC10/Ankyrin (ANK)
      repeats domain. Treatment of WAP-Int3 tumor bearing mice with an IKK inhibitor
      resulted in tumor regression. In a soft agar assay, treatment of HC11-Int3 cells
      with P50-siRNA caused a significant decrease in colony formation. In addition,
      Wap-Int3/P50 knockout mice did not develop mammary tumors. This data indicates
      that the activation of NF-kappaB canonical signaling by Notch-4/Int3 is ANK
      repeats dependent, Rbpj-independent, and is mediated by IKK activation and P50
      phosphorylation causing mammary tumorigenesis.

PMID- 29057905
TI  - Albumin uptake in human podocytes: a possible role for the cubilin-amnionless
      (CUBAM) complex.
AB  - Albumin re-uptake is a receptor-mediated pathway located in renal proximal
      tubuli. There is increasing evidence of glomerular protein handling by podocytes,
      but little is known about the mechanism behind this process. In this study, we
      found that human podocytes in vitro are committed to internalizing albumin
      through a receptor-mediated mechanism even after exposure to low doses of
      albumin. We show that these cells express cubilin, megalin, ClC-5, amnionless and
      Dab2, which are partners in the tubular machinery. Exposing human podocytes to
      albumin overload prompted an increase in CUBILIN, AMNIONLESS and CLCN5 gene
      expression. Inhibiting cubilin led to a reduction in albumin uptake, highlighting
      its importance in this mechanism. We demonstrated that human podocytes are
      committed to performing endocytosis via a receptor-mediated mechanism even in the
      presence of low doses of albumin. We also disclosed that protein overload first
      acts on the expression of the cubilin-amnionless (CUBAM) complex in these cells,
      then involves the ClC-5 channel, providing the first evidence for a possible role
      of the CUBAM complex in albumin endocytosis in human podocytes.

PMID- 29057906
TI  - Distinct retinoic acid receptor (RAR) isotypes control differentiation of
      embryonal carcinoma cells to dopaminergic or striatopallidal medium spiny
      neurons.
AB  - Embryonal carcinoma (EC) cells are pluripotent stem cells extensively used for
      studies of cell differentiation. Although retinoic acid (RA) is a powerful
      inducer of neurogenesis in EC cells, it is not clear what specific neuronal
      subtypes are generated and whether different RAR isotypes may contribute to such
      neuronal diversification. Here we show that RA treatment during EC embryoid body
      formation is a highly robust protocol for generation of striatal-like GABAergic
      neurons which display molecular characteristics of striatopallidal medium spiny
      neurons (MSNs), including expression of functional dopamine D2 receptor. By using
      RARalpha, beta and gamma selective agonists we show that RARgamma is the
      functionally dominant RAR in mediating RA control of early molecular determinants
      of MSNs leading to formation of striatopallidal-like neurons. In contrast,
      activation of RARalpha is less efficient in generation of this class of neurons,
      but is essential for differentiation of functional dopaminergic neurons, which
      may correspond to a subpopulation of inhibitory dopaminergic neurons expressing
      glutamic acid decarboxylase in vivo.

PMID- 29057907
TI  - Establishing the behavioural limits for countershaded camouflage.
AB  - Countershading is a ubiquitous patterning of animals whereby the side that
      typically faces the highest illumination is darker. When tuned to specific
      lighting conditions and body orientation with respect to the light field,
      countershading minimizes the gradient of light the body reflects by
      counterbalancing shadowing due to illumination, and has therefore classically
      been thought of as an adaptation for visual camouflage. However, whether and how
      crypsis degrades when body orientation with respect to the light field is non
      optimal has never been studied. We tested the behavioural limits on body
      orientation for countershading to deliver effective visual camouflage. We asked
      human participants to detect a countershaded target in a simulated three
      dimensional environment. The target was optimally coloured for crypsis in a
      reference orientation and was displayed at different orientations. Search
      performance dramatically improved for deviations beyond 15 degrees. Detection
      time was significantly shorter and accuracy significantly higher than when the
      target orientation matched the countershading pattern. This work demonstrates the
      importance of maintaining body orientation appropriate for the displayed
      camouflage pattern, suggesting a possible selective pressure for animals to
      orient themselves appropriately to enhance crypsis.

PMID- 29057908
TI  - Silencing Nfix rescues muscular dystrophy by delaying muscle regeneration.
AB  - Muscular dystrophies are severe disorders due to mutations in structural genes,
      and are characterized by skeletal muscle wasting, compromised patient mobility,
      and respiratory functions. Although previous works suggested enhancing
      regeneration and muscle mass as therapeutic strategies, these led to no long-term
      benefits in humans. Mice lacking the transcription factor Nfix have delayed
      regeneration and a shift toward an oxidative fiber type. Here, we show that
      ablating or silencing the transcription factor Nfix ameliorates pathology in
      several forms of muscular dystrophy. Silencing Nfix in postnatal dystrophic mice,
      when the first signs of the disease already occurred, rescues the pathology and,
      conversely, Nfix overexpression in dystrophic muscles increases regeneration and
      markedly exacerbates the pathology. We therefore offer a proof of principle for a
      novel therapeutic approach for muscular dystrophies based on delaying muscle
      regeneration.

PMID- 29057909
TI  - Inferred father-to-son transmission of herpes simplex virus results in near
      perfect preservation of viral genome identity and in vivo phenotypes.
AB  - High throughout sequencing has provided an unprecedented view of the circulating
      diversity of all classes of human herpesviruses. For herpes simplex virus 1 (HSV
      1), we and others have previously published data demonstrating sequence diversity
      between hosts. However the extent of variation during transmission events, or in
      one host over years of chronic infection, remain unknown. Here we present an
      initial example of full characterization of viruses isolated from a father to son
      transmission event. The likely occasion of transmission occurred 17 years before
      the strains were isolated, enabling a first view of the degree of virus
      conservation after decades of recurrences, including transmission and adaptation
      to a new host. We have characterized the pathogenicity of these strains in a
      mouse ocular model of infection, and sequenced the full viral genomes.
      Surprisingly, we find that these two viruses have preserved their phenotype and
      genotype nearly perfectly during inferred transmission from father to son, and
      during nearly two decades of episodes of recurrent disease in each human host.
      Given the close genetic relationship of these two hosts, it remains to be seen
      whether or not this conservation of sequence will occur during non-familial
      transmission events.

PMID- 29057910
TI  - Investigation of foaming causes in three mesophilic food waste digesters: reactor
      performance and microbial analysis.
AB  - Foaming negatively affects anaerobic digestion of food waste (FW). To identify
      the causes of foaming, reactor performance and microbial community dynamics were
      investigated in three mesophilic digesters treating FW. The digesters were
      operated under different modes, and foaming was induced with several methods.
      Proliferation of specific bacteria and accumulation of surface active materials
      may be the main causes of foaming. Volatile fatty acids (VFAs) and total ammonia
      nitrogen (TAN) accumulated in these reactors before foaming, which may have
      contributed to foam formation by decreasing the surface tension of sludge and
      increasing foam stability. The relative abundance of acid-producing bacteria
      (Petrimonas, Fastidiosipila, etc.) and ammonia producers (Proteiniphilum, Gelria,
      Aminobacterium, etc.) significantly increased after foaming, which explained the
      rapid accumulation of VFAs and NH4+ after foaming. In addition, the proportions
      of microbial genera known to contribute to foam formation and stabilization
      significantly increased in foaming samples, including bacteria containing mycolic
      acid in cell walls (Actinomyces, Corynebacterium, etc.) and those capable of
      producing biosurfactants (Corynebacterium, Lactobacillus, 060F05-B-SD-P93, etc.).
      These findings improve the understanding of foaming mechanisms in FW digesters
      and provide a theoretical basis for further research on effective suppression and
      early warning of foaming.

PMID- 29057911
TI  - Genetic association study identified a 20 kb regulatory element in WLS associated
      with osteoporosis and bone mineral density in Han Chinese.
AB  - Previous studies have linked the WNT pathway and human skeleton formation;
      therefore, genes related to WNT might contribute to the onset and development of
      osteoporosis. In this study, we investigated the potential genetic association of
      WLS, which encodes an important mediator in the WNT pathway, with osteoporosis
      and its related quantitative traits in a sample of 6,620 individuals from Han
      Chinese population. A two-stage approach, with a discovery stage with 859 cases
      and 1,690 controls and a validation stage with 1,039 cases and 3,032 controls,
      was applied in the study. Forty SNPs were genotyped in the discovery stage. The
      intronic SNP rs2566752 was identified to be significantly associated with
      osteoporosis (ORdiscovery = 0.78, P discovery = 3.73 * 10-5; ORvalidation = 0.80,
      P validation = 1.96 * 10-5). Two SNPs surrounding rs2566752 (in addition to this
      SNP itself) were identified to be associated with bone mineral density. In
      addition, we have identified a 20 kb peak region of H3K27Ac histone mark
      enrichment between rs2772304 and rs2566752. Our study suggested that WLS is an
      important locus for osteoporosis and its related quantitative phenotypes in Han
      Chinese population. Additional sequencing-based studies are needed to investigate
      the genetic architecture of this regulatory region and its relationship with
      osteoporosis-related phenotypes.

PMID- 29057913
TI  - Heterochronic evolution explains novel body shape in a Triassic coelacanth from
      Switzerland.
AB  - A bizarre latimeriid coelacanth fish from the Middle Triassic of Switzerland
      shows skeletal features deviating from the uniform anatomy of coelacanths. The
      new form is closely related to a modern-looking coelacanth found in the same
      locality and differences between both are attributed to heterochronic evolution.
      Most of the modified osteological structures in the new coelacanth have their
      developmental origin in the skull/trunk interface region in the embryo. Change in
      the expression of developmental patterning genes, specifically the Pax1/9 genes,
      may explain a rapid evolution at the origin of the new coelacanth. This species
      broadens the morphological disparity range within the lineage of these 'living
      fossils' and exemplifies a case of rapid heterochronic evolution likely trigged
      by minor changes in gene expression.

PMID- 29057912
TI  - Posttranslational modifications of blood-derived alpha-synuclein as biochemical
      markers for Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder known for
      the typical motor features associated. Pathologically, it is characterized by the
      intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy
      neurites. Currently, there are no established biochemical markers for diagnosing
      or for following disease progression, a major limitation for the clinical
      practice. Posttranslational modifications (PTMs) in aSyn have been identified and
      implicated on its pathobiology. Since aSyn is abundant in blood erythrocytes, we
      aimed to evaluate whether PTMs of aSyn in the blood might hold value as a
      biomarker for PD. We examined 58 patients with PD and 30 healthy age-matched
      individuals. We found that the levels of Y125 phosphorylated, Y39 nitrated, and
      glycated aSyn were increased in PD, while those of SUMO were reduced. A
      combinatory analysis of the levels of these PTMs resulted in an increased
      sensitivity, with an area under curve (AUC) of 0.843 for PD versus healthy
      controls, and correlated with disease severity and duration. We conclude that the
      levels of these selected PTMs hold strong potential as biochemical markers for
      PD. Ultimately, our findings might facilitate the monitoring of disease
      progression in clinical trials, opening the possibility for developing more
      effective therapies against PD.

PMID- 29057914
TI  - Superelasticity and cryogenic linear shape memory effects of CaFe2As2.
AB  - Shape memory materials have the ability to recover their original shape after a
      significant amount of deformation when they are subjected to certain stimuli, for
      instance, heat or magnetic fields. However, their performance is often limited by
      the energetics and geometry of the martensitic-austenitic phase transformation.
      Here, we report a unique shape memory behavior in CaFe2As2, which exhibits
      superelasticity with over 13% recoverable strain, over 3 GPa yield strength,
      repeatable stress-strain response even at the micrometer scale, and cryogenic
      linear shape memory effects near 50 K. These properties are acheived through a
      reversible uni-axial phase transformation mechanism, the tetragonal/orthorhombic
      to-collapsed-tetragonal phase transformation. Our results offer the possibility
      of developing cryogenic linear actuation technologies with a high precision and
      high actuation power per unit volume for deep space exploration, and more
      broadly, suggest a mechanistic path to a class of shape memory materials,
      ThCr2Si2-structured intermetallic compounds.

PMID- 29057915
TI  - Mast cell involvement in glucose tolerance impairment caused by chronic mild
      stress with sleep disturbance.
AB  - We have developed a chronic mild stress (MS) mouse model by simply rearing mice
      on a wire net for 3 weeks and investigated the effects of MS on glucose
      homeostasis and sleep. MS mice showed impaired glucose tolerance and disturbed
      sleep. One-week treatment with a histamine H1 receptor antagonist (H1RA)
      ameliorated the glucose intolerance and improved sleep quality in MS mice. MS
      mice showed an increased number of mast cells in both adipose tissue and the
      brain. Inhibition of mast cell function ameliorated the impairment in both
      glucose tolerance and sleep. Together, these findings indicate that mast cells
      may represent an important pathophysiological mediator in sleep and energy
      homeostasis.

PMID- 29057916
TI  - Engineering the internal surfaces of three-dimensional nanoporous catalysts by
      surfactant-modified dealloying.
AB  - Tuning surface structures by bottom-up synthesis has been demonstrated as an
      effective strategy to improve the catalytic performances of nanoparticle
      catalysts. Nevertheless, the surface modification of three-dimensional nanoporous
      metals, fabricated by a top-down dealloying approach, has not been achieved
      despite great efforts devoted to improving the catalytic performance of three
      dimensional nanoporous catalysts. Here we report a surfactant-modified dealloying
      method to tailor the surface structure of nanoporous gold for amplified
      electrocatalysis toward methanol oxidation and oxygen reduction reactions. With
      the assistance of surfactants, {111} or {100} faceted internal surfaces of
      nanoporous gold can be realized in a controllable manner by optimizing dealloying
      conditions. The surface modified nanoporous gold exhibits significantly enhanced
      electrocatalytic activities in comparison with conventional nanoporous gold. This
      study paves the way to develop high-performance three-dimensional nanoporous
      catalysts with a tunable surface structure by top-down dealloying for efficient
      chemical and electrochemical reactions.

PMID- 29057917
TI  - Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in
      cattle pre-exposed to bovine RSV.
AB  - Human respiratory syncytial virus (hRSV) is responsible for serious lower
      respiratory tract disease in infants and in older adults, and remains an
      important vaccine need. RSV fusion (F) glycoprotein is a key target for
      neutralizing antibodies. RSV F stabilized in its pre-fusion conformation (DS-Cav1
      F) induces high neutralizing antibody titers in naive animals, but it remains
      unknown to what extent pre-fusion F can boost pre-existing neutralizing responses
      in RSV seropositive adults. We here assess DS-Cav1 F immunogenicity in
      seropositive cattle pre-exposed to bovine RSV, a virus closely related to hRSV. A
      single immunization with non-adjuvanted DS-Cav1 F strongly boosts RSV
      neutralizing responses, directed towards pre-fusion F-specific epitopes, whereas
      a post-fusion F is unable to do so. Vaccination with pre-fusion F thus represents
      a promising strategy for maternal immunization and for other RSV vaccine target
      populations such as older adults.

PMID- 29057919
TI  - Identification and Validation of a PD-L1 Binding Peptide for Determination of
      PDL1 Expression in Tumors.
AB  - Blocking the interaction between Programmed Death Ligand 1 (PD-L1) and its
      receptor, PD-1, is an effective method of treating many types of cancers. Certain
      tumors overexpress PD-L1, causing host immune cells that express PD-1 to bind PD
      L1 and cease killing the tumor. Inhibition of PD-L1 and PD-1 binding can restore
      host immunity towards tumor killing, and many new drugs have been developed to
      target this interaction. Current methods of PD-L1 diagnosis have shown to vary
      based on the antibody, detection kit brand, antigen retrieval method, and
      clinically defined methods by the FDA. To refine detection of PD-L1, we have
      identified a peptide, RK-10, and used it to detect PD-L1 expressing tumors with
      immunohistochemistry or flow cytometry. Flow cytometry was performed on cell
      lines and patient tissues using a fluorescent peptide (RK-10-Cy5).
      Immunohistochemistry using a biotin-modified peptide (RK-10-Biotin) was tested
      against the FDA-approved SP263 clone on biopsied patient tissues. For this study,
      we evaluated specificity of RK-10 using IHC in over 200 patient tissues,
      including NSCLC and Hodgkin's Lymphoma. RK-10 shows staining in the tumor regions
      of FFPE tissues where the SP263 kit does not. RK-10-Cy5 peptide also demonstrates
      PD-L1 detection in NSCLC, breast, squamous cell carcinoma, and melanoma.

PMID- 29057918
TI  - YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer.
AB  - Recognition of modified histones by "reader" proteins constitutes a key mechanism
      regulating diverse chromatin-associated processes important for normal and
      neoplastic development. We recently identified the YEATS domain as a novel
      acetyllysine-binding module; however, the functional importance of YEATS domain
      containing proteins in human cancer remains largely unknown. Here, we show that
      the YEATS2 gene is highly amplified in human non-small cell lung cancer (NSCLC)
      and is required for cancer cell growth and survival. YEATS2 binds to acetylated
      histone H3 via its YEATS domain. The YEATS2-containing ATAC complex co-localizes
      with H3K27 acetylation (H3K27ac) on the promoters of actively transcribed genes.
      Depletion of YEATS2 or disruption of the interaction between its YEATS domain and
      acetylated histones reduces the ATAC complex-dependent promoter H3K9ac levels and
      deactivates the expression of essential genes. Taken together, our study
      identifies YEATS2 as a histone H3K27ac reader that regulates a transcriptional
      program essential for NSCLC tumorigenesis.

PMID- 29057920
TI  - Halogenated Chrysins Inhibit Dengue and Zika Virus Infectivity.
AB  - Dengue virus infection is a global threat for which no specific treatment has not
      been established. Previous reports suggested chrysin and flavanone derivatives
      were potential flaviviral inhibitors. Here, we reported two halogenated chrysins,
      abbreviated FV13 and FV14, were highly potent against DENV1-4 and ZIKV
      infectivities with the FV13 EC50 values of 2.30 +/- 1.04, 1.47 +/- 0.86, 2.32 +/-
      1.46, 1.78 +/- 0.72 and 1.65 +/- 0.86 uM; and FV14 EC50 values of 2.30 +/- 0.92,
      2.19 +/- 0.31, 1.02 +/- 0.31, 1.29 +/- 0.60 and 1.39 +/- 0.11 uM, respectively.
      The CC50s to LLC/MK2 of FV13 and FV14 were 44.28 +/- 2.90 MUM, 42.51 +/- 2.53 uM,
      respectively. Mechanism of drug action studies suggested multiple targets but
      maximal efficiency was achieved with early post infection treatment. This is the
      first report showing a high potency of halogenated chrysins for development as a
      broad-spectrum anti-flaviviral drug.

PMID- 29057921
TI  - The recovery status from delayed graft function can predict long-term outcome
      after deceased donor kidney transplantation.
AB  - The effect of delayed graft function (DGF) recovery on long-term graft outcome is
      unclear. The aim of this study was to examine the association of DGF recovery
      status with long-term outcome. We analyzed 385 recipients who underwent single
      kidney transplantation from brain-dead donors between 2004 and 2015. Patients
      were grouped according to renal function at 1 month post-transplantation: control
      (without DGF); recovered DGF (glomerular filtration rate [GFR] >= 30 mL/min/1.73
      m2); and incompletely recovered DGF group (GFR < 30 mL/min/1.73 m2). DGF occurred
      in 104 of 385 (27%) recipients. Of the DGF patients, 70 recovered from DGF and 34
      incompletely recovered from DGF. Death-censored graft survival rates for control,
      recovered DGF, and incompletely recovered DGF groups were 95.3%, 94.7%, and
      80.7%, respectively, at 5 years post-transplantation (P = 0.003). Incompletely
      recovered DGF was an independent risk factor for death-censored graft loss (HR =
      3.410, 95%CI, 1.114-10.437). DGF was associated with increased risk for patient
      death regardless of DGF recovery status. Mean GFRs at 5 years were 65.5 +/- 20.8,
      62.2 +/- 27.0, and 45.8 +/- 15.4 mL/min/1.73 m2 for control, recovered, and
      incompletely recovered DGF groups, respectively (P < 0.001). Control group and
      recovered DGF patients had similar renal outcomes. However, DGF was associated
      with increased risk for patient death regardless of DGF recovery status.

PMID- 29057922
TI  - A trade-off between cognitive and physical performance, with relative
      preservation of brain function.
AB  - Debate surrounds the issue of how the large, metabolically expensive brains of
      Homo sapiens can be energetically afforded. At the evolutionary level, decreased
      investment in muscularity, adiposity and the digestive tract allow for a larger
      brain. Developmentally, high neo-natal adiposity and preferential distribution of
      resources to the brain provide an energetic buffer during times of environmental
      stress. Through an experimental design, we investigated the hypothesis of a trade
      off involving brain and muscle at the acute level in humans. Mental performance
      was measured by a free-recall test, and physical performance by power output on
      an indoor rowing ergometer. Sixty-two male student rowers performed the two tests
      in isolation, and then again simultaneously. Paired samples t-tests revealed that
      both power output and mental performance reduced when tested together compared to
      in isolation (t(61) = 9.699, p < 0.001 and t(61) = 8.975, p < 0.001).
      Furthermore, the decrease in physical performance was greater than the decrease
      in mental performance (t(61) = -2.069, p = 0.043). This is the first
      investigation to demonstrate an acute level trade-off between these two
      functions, and provides support for the selfish brain hypothesis due to the
      relative preservation of cognitive function over physical power output. The
      underlying mechanism is unclear, and requires further work.

PMID- 29057923
TI  - Supervised Quantum Learning without Measurements.
AB  - We propose a quantum machine learning algorithm for efficiently solving a class
      of problems encoded in quantum controlled unitary operations. The central
      physical mechanism of the protocol is the iteration of a quantum time-delayed
      equation that introduces feedback in the dynamics and eliminates the necessity of
      intermediate measurements. The performance of the quantum algorithm is analyzed
      by comparing the results obtained in numerical simulations with the outcome of
      classical machine learning methods for the same problem. The use of time-delayed
      equations enhances the toolbox of the field of quantum machine learning, which
      may enable unprecedented applications in quantum technologies.

PMID- 29057924
TI  - Automatic auditory and somatosensory brain responses in relation to cognitive
      abilities and physical fitness in older adults.
AB  - In normal ageing, structural and functional changes in the brain lead to an
      altered processing of sensory stimuli and to changes in cognitive functions. The
      link between changes in sensory processing and cognition is not well understood,
      but physical fitness is suggested to be beneficial for both. We recorded event
      related potentials to somatosensory and auditory stimuli in a passive change
      detection paradigm from 81 older and 38 young women and investigated their
      associations with cognitive performance. In older adults also associations to
      physical fitness were studied. The somatosensory mismatch response was attenuated
      in older adults and it associated with executive functions. Somatosensory P3a did
      not show group differences, but in older adults, it associated with physical
      fitness. Auditory N1 and P2 responses to repetitive stimuli were larger in
      amplitude in older than in young adults. There were no group differences in the
      auditory mismatch negativity, but it associated with working memory capacity in
      young but not in older adults. Our results indicate that in ageing, changes in
      stimulus encoding and deviance detection are observable in electrophysiological
      responses to task-irrelevant somatosensory and auditory stimuli, and the higher
      somatosensory response amplitudes are associated with better executive functions
      and physical fitness.

PMID- 29057926
TI  - Engraftment and morphological development of vascularized human iPS cell-derived
      3D-cardiomyocyte tissue after xenotransplantation.
AB  - One of the major challenges in cell-based cardiac regenerative medicine is the in
      vitro construction of three-dimensional (3D) tissues consisting of induced
      pluripotent stem cell-derived cardiomyocyte (iPSC-CM) and a blood vascular
      network supplying nutrients and oxygen throughout the tissue after implantation.
      We have successfully built a vascularized iPSC-CM 3D-tissue using our validated
      cell manipulation technique. In order to evaluate an availability of the 3D
      tissue as a biomaterial, functional morphology of the tissues was examined by
      light and transmission electron microscopy through their implantation into the
      rat infarcted heart. Before implantation, the tissues showed distinctive
      myofibrils within iPSC-CMs and capillary-like endothelial tubes, but their
      profiles were still like immature. In contrast, engraftment of the tissues to the
      rat heart led the iPSC-CMs and endothelial tubes into organization of cell
      organelles and junctional apparatuses and prompt development of capillary network
      harboring host blood supply, respectively. A number of capillaries in the
      implanted tissues were derived from host vascular bed, whereas the others were
      likely to be composed by fusion of host and implanted endothelial cells. Thus,
      our vascularized iPSC-CM 3D-tissues may be a useful regenerative paradigm which
      will require additional expanded and long-term studies.

PMID- 29057925
TI  - Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of
      Bcl-xL.
AB  - Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H),
      which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2
      HG). In six model systems, including patient-derived stem cell-like glioblastoma
      cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1
      mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with
      mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and
      specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL
      inhibition-mediated apoptosis. Addition of 2-HG to glioblastoma cultures
      recapitulates the effects of the IDH mutation on intrinsic apoptosis, shuts down
      oxidative phosphorylation and reduces ATP levels in glioblastoma cells. 2-HG
      mediated energy depletion activates AMPK (Threonine 172), blunting protein
      synthesis and mTOR signaling, culminating in a decline of Mcl-1. In an orthotopic
      glioblastoma xenograft model expressing mutated IDH1, Bcl-xL inhibition leads to
      long-term survival. These results demonstrate that IDH1-mutated gliomas are
      particularly vulnerable to Bcl-xL inhibition.

PMID- 29057927
TI  - Use of the relative release index for histamine in LAD2 cells to evaluate the
      potential anaphylactoid effects of drugs.
AB  - Anaphylactoid reactions are common clinical acute adverse drug reactions that can
      exacerbate a patient's condition and produce effects that may become life
      threatening. Therefore, it is important to establish a novel method to evaluate
      drugs for anaphylactoid reactions. In this study, we developed a sensitive and
      rapid method to detect histamine release from LAD2 cells using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) and constructed a relative
      release index based on various release curve parameters, including allergen
      release time and sudden change rate, to evaluate the potential and strength of
      allergen-induced anaphylactoid reactions. This LAD2 release model was used to
      evaluate anaphylactoid reactions induced by ciprofloxacin, norfloxacin,
      lomefloxacin, moxifloxacin, and baicalin. The results positively correlated with
      those obtained with an Evans blue ear test and negatively correlated with the
      Ca2+ influx EC50. In summary, the current study established a novel in vitro
      method to analyze the properties of histamine release from LAD2 cells and
      characterize the sensitization and strength of sensitization of drugs or
      components that may induce anaphylactoid reactions.

PMID- 29057928
TI  - The rice TRIANGULAR HULL1 protein acts as a transcriptional repressor in
      regulating lateral development of spikelet.
AB  - As a basic unit of rice inflorescence, spikelet has profound influence on grain
      size, weight and yield. The molecular mechanism underlying spikelet development
      has not been fully elucidated. Here, we identified four allelic rice mutants, s2
      89, xd151, xd281 and xd425, which exhibited reduced width of spikelet, especially
      in the apical region. Map-based cloning revealed that all these mutants had
      missense mutation in the TRIANGULAR HULL1 (TH1) gene, encoding an ALOG family
      protein. TH1 has been shown to regulate the lateral development of spikelet, but
      its mode of action remains unclear. Microscopic analysis revealed that the
      reduction in spikelet width was caused by decreased cell size rather than cell
      division. The TH1 protein was shown to localize in the nucleus and possess
      transcriptional repression activity. TH1 could form a homodimer and point
      mutation in the s2-89, xd281 and xd425 mutant inhibited homodimerization. The
      transcriptional repression activity of TH1 was partially relieved by the
      His129Tyr substitution in the s2-89 mutant. Fusion of an exogenous EAR
      transcription suppression domain to the mutant protein TH1s2-89 could largely
      complemented the narrow spikelet phenotype. These results indicate that TH1
      functions as a transcription repressor and regulates cell expansion during the
      lateral development of spikelet.

PMID- 29057929
TI  - Grain boundary mediated hydriding phase transformations in individual
      polycrystalline metal nanoparticles.
AB  - Grain boundaries separate crystallites in solids and influence material
      properties, as widely documented for bulk materials. In nanomaterials, however,
      investigations of grain boundaries are very challenging and just beginning. Here,
      we report the systematic mapping of the role of grain boundaries in the
      hydrogenation phase transformation in individual Pd nanoparticles. Employing
      multichannel single-particle plasmonic nanospectroscopy, we observe large
      variation in particle-specific hydride-formation pressure, which is absent in
      hydride decomposition. Transmission Kikuchi diffraction suggests direct
      correlation between length and type of grain boundaries and hydride-formation
      pressure. This correlation is consistent with tensile lattice strain induced by
      hydrogen localized near grain boundaries as the dominant factor controlling the
      phase transition during hydrogen absorption. In contrast, such correlation is
      absent for hydride decomposition, suggesting a different phase-transition
      pathway. In a wider context, our experimental setup represents a powerful
      platform to unravel microstructure-function correlations at the individual
      nanoparticle level.

PMID- 29057930
TI  - Recurrent water deficit causes epigenetic and hormonal changes in citrus plants.
AB  - The present study evaluated the physiological, molecular and hormonal parameters
      from scion/rootstock interaction of citrus plants during recurrent water deficit.
      Responses of the Valencia (VO) scion variety grafted on two rootstocks with
      different soil water extraction capacities, Rangpur Lime (RL) and Sunki Maravilha
      (SM), during three successive periods of water deficit: plants exposed to a
      single episode of water deficit (WD1) and plants exposed to two (WD2) and three
      (WD3) recurrent periods of WD were compared. The combinations VO/RL and VO/SM
      presented polymorphic alterations of epigenetic marks and hormonal (i.e. abscisic
      acid, auxins and salicylicacid) profiles, which were particularly prominent when
      VO/SM plantswere exposed toWD3 treatment. Upon successive drought events, the
      VO/SM combination presented acclimatization characteristics that enable higher
      tolerance to water deficit by increasing transpiration (E), stomatal conductance
      (g s ) and photosynthetic rate (A), which in turn may have facilitated the whole
      plant survival. Besides providing comprehensive data on the scion/rootstock
      interactions upon successive stress events, this study brings the first dataset
      suggesting that epigenetic alterations in citrus plants triggered by recurrent
      water deficit lead to improved drought tolerance in this crop species.

PMID- 29057931
TI  - Nucleotide and receptor density modulate binding of bacterial division FtsZ
      protein to ZipA containing lipid-coated microbeads.
AB  - ZipA protein from Escherichia coli is one of the essential components of the
      division proto-ring that provides membrane tethering to the septation FtsZ
      protein. A sedimentation assay was used to measure the equilibrium binding of
      FtsZ-GDP and FtsZ-GTP to ZipA immobilized at controlled densities on the surface
      of microbeads coated with a phospholipid mixture resembling the composition of E.
      coli membrane. We found that for both nucleotide-bound species, the amount of
      bound FtsZ exceeds the monolayer capacity of the ZipA immobilized beads at high
      concentrations of free FtsZ. In the case of FtsZ-GDP, equilibrium binding does
      not appear to be saturable, whereas in the case of FtsZ-GTP equilibrium binding
      appears to be saturable. The difference between the two modes of binding is
      attributed to the difference between the composition of oligomers of free FtsZ
      GDP and free FtsZ-GTP formed in solution.

PMID- 29057932
TI  - A novel scoring system to analyze combined effect of lifestyle factors on
      pancreatic cancer risk: a retrospective case-control study.
AB  - Although several risk factors for the onset of pancreatic ductal adenocarcinoma
      (PDAC) have been identified, currently, no scoring system to systemically
      evaluate the risk of PDAC has been established. In this study, we aimed to use a
      population of over 1200 patients to build a novel scoring system, and evaluated
      combined effects of risk factors for PDAC patients.A set of 4904 participants
      including 1274 PDAC patients and 3630 non-cancer individuals were recruited for
      the single-center study over 17-year period (1997~2013). Systematic logical
      analysis were presented for case and control groups, and a risk rating system was
      constructed to assess combined risk factors. Seven independent risk factors were
      identified with the increased risk of PDAC, were selected into the risk score. A
      merged risk assessment model was established, demonstrating significantly
      increased PDAC risk in following a number of rising scores. Individuals with
      scores from 1 to more than 4, the responding OR (95% CI) were 3.06 (2.57~3.65),
      7.08 (5.63~8.91), 22.4 (14.2~35.4), and 31.4 (12.7~77.5), respectively. The
      integer-based risk score in the study can be used for risk stratification to
      accurately evaluate PDAC occurrence at an early stage. This scoring system
      provides an accurate risk assessment of PDAC risk.

PMID- 29057933
TI  - Determination of the Genome and Primary Transcriptome of Syngas Fermenting
      Eubacterium limosum ATCC 8486.
AB  - Autotrophic conversion of CO2 to value-added biochemicals has received
      considerable attention as a sustainable route to replace fossil fuels.
      Particularly, anaerobic acetogenic bacteria are naturally capable of reducing CO2
      or CO to various metabolites. To fully utilize their biosynthetic potential, an
      understanding of acetogenesis-related genes and their regulatory elements is
      required. Here, we completed the genome sequence of the syngas fermenting
      Eubacterium limosum ATCC 8486 and determined its transcription start sites (TSS).
      We constructed a 4.4 Mb long circular genome with a GC content of 47.2% and 4,090
      protein encoding genes. To understand the transcriptional and translational
      regulation, the primary transcriptome was augmented, identifying 1,458 TSSs
      containing a high pyrimidine (T/C) and purine nucleotide (A/G) content at the -1
      and +1 position, respectively, along with 1,253 5'-untranslated regions, and
      principal promoter elements such as -10 (TATAAT) and -35 (TTGACA), and Shine
      Dalgarno motifs (GGAGR). Further analysis revealed 93 non-coding RNAs, including
      one for potential transcriptional regulation of the hydrogenase complex via
      interaction with molybdenum or tungsten cofactors, which in turn controls formate
      dehydrogenase activity of the initial step of Wood-Ljungdahl pathway. Our results
      provide comprehensive genomic information for strain engineering to enhance the
      syngas fermenting capacity of acetogenic bacteria.

PMID- 29057935
TI  - Gpbar1 agonism promotes a Pgc-1alpha-dependent browning of white adipose tissue
      and energy expenditure and reverses diet-induced steatohepatitis in mice.
AB  - Gpbar1 is a bile acid activated receptor for secondary bile acids. Here we have
      investigated the mechanistic role of Gpbar1 in the regulation of adipose tissues
      functionality in a murine model of steatohepatitis (NASH). Feeding wild type and
      Gpbar1-/- mice with a high fat diet-fructose (HFD-F) lead to development of NASH
      like features. Treating HFD-F mice with 6beta-ethyl-3a,7b-dihydroxy-5b-cholan-24
      ol (BAR501), a selective Gpbar1-ligand, reversed insulin resistance and
      histologic features of NASH, increased the weight of epWAT and BAT functionality
      and promoted energy expenditure and the browning of epWAT as assessed by
      measuring expression of Ucp1 and Pgc-1alpha. The beneficial effects of BAR501
      were lost in Gpbar1-/- mice. In vitro, BAR501 promoted the browning of 3T3-L1
      cells a pre-adipocyte cell line and recruitment of CREB to the promoter of Pgc
      1alpha. In conclusion, Gpbar1 agonism ameliorates liver histology in a rodent
      model of NASH and promotes the browning of white adipose tissue.

PMID- 29057934
TI  - PTP4A1 promotes TGFbeta signaling and fibrosis in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of
      skin and internal organs. Protein tyrosine phosphatases have received little
      attention in the study of SSc or fibrosis. Here, we show that the tyrosine
      phosphatase PTP4A1 is highly expressed in fibroblasts from patients with SSc.
      PTP4A1 and its close homolog PTP4A2 are critical promoters of TGFbeta signaling
      in primary dermal fibroblasts and of bleomycin-induced fibrosis in vivo. PTP4A1
      promotes TGFbeta signaling in human fibroblasts through enhancement of ERK
      activity, which stimulates SMAD3 expression and nuclear translocation. Upstream
      from ERK, we show that PTP4A1 directly interacts with SRC and inhibits SRC basal
      activation independently of its phosphatase activity. Unexpectedly, PTP4A2
      minimally interacts with SRC and does not promote the SRC-ERK-SMAD3 pathway.
      Thus, in addition to defining PTP4A1 as a molecule of interest for TGFbeta
      dependent fibrosis, our study provides information regarding the functional
      specificity of different members of the PTP4A subclass of phosphatases.

PMID- 29057936
TI  - Glioblastoma cancer stem cell lines express functional acid sensing ion channels
      ASIC1a and ASIC3.
AB  - Acidic microenvironment is commonly observed in tumour tissues, including
      glioblastoma (GBM), the most aggressive and lethal brain tumour in adults. Acid
      sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels,
      which are sensors of extracellular protons. Here we studied and functionally
      characterized ASICs in two primary glioblastoma stem cell lines as cell culture
      models. We detected transcripts of the ACCN2 and ACCN3 genes, coding for ASIC1
      and ASIC3, respectively, but not transcripts of ACCN1 (coding for ASIC2).
      Available microarray data confirmed that ACCN1 is downregulated in glioma.
      Western blotting confirmed expression of ASIC1 and ASIC3, the most proton
      sensitive ASICs, in both GBM cell lines. We characterized ASICs functionally
      using whole-cell patch clamp and detected different types of acid-sensitive
      currents. Some of these currents had kinetics typical for ASICs and were
      sensitive to specific toxin inhibitors of ASIC1a or ASIC3, demonstrating that the
      GBM cell lines express functional ASIC1a and ASIC3 that may enable GBM cells to
      sensitively detect extracellular pH in a tumour tissue. Microarray data revealed
      that expression of ACCN2 and ACCN3 is associated with improved survival of
      patients suffering from gliomas, suggesting that preserved susceptibility to
      extracellular pH may impair tumour growth.

PMID- 29057937
TI  - Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of
      Japanese encephalitis from an endemic population of India.
AB  - Japanese encephalitis (JE) is a major contributor for viral encephalitis in Asia.
      Vaccination programme has limited success for largely populated JE endemic
      countries like India and disease exposure is unavoidable. Involvement of
      chemokines and its co-receptors for adverse prognosis of JE have been documented
      both in vitro and in vivo. Identification of the genetic predisposing factor for
      JE infection in humans is crucial but not yet established. Therefore, we
      investigated the association of single nucleotide polymorphisms (SNPs) in
      chemokines (CCL2 and CCL5) and its co-receptors (CCR2 and CCR5) with their
      protein level for JE. The study enrolled 87 symptomatic JE cases (mild: severe =
      24:63) and 94 asymptomatic controls. Our study demonstrated that CCL2
      (rs1024611G), CCL5 (rs2280788G) and CCR2 (rs1799864A) significantly associated
      with JE (Odds ratio = 1.63, 2.95 and 2.62, respectively and P = 0.045, P = 0.05
      and P = 0.0006, respectively). The study revealed that rs1024611G allele was
      associated with elevated level of CCL2. CCL5 elevation associated with JE
      mortality having a Cox proportional hazard of 1.004 (P = 0.033). In conclusion,
      SNPs of chemokine viz. CCL2 (rs1024611G) and its receptor CCR2 (rs1799864A)
      significantly associated with JE which may serve as possible genetic predisposing
      factor and CCL5 protein level may act as marker for disease survival.

PMID- 29057938
TI  - Focal Spot and Wavefront Sensing of an X-Ray Free Electron laser using Ronchi
      shearing interferometry.
AB  - The Linac Coherent Light Source (LCLS) is an X-ray source of unmatched
      brilliance, that is advancing many scientific fields at a rapid pace. The highest
      peak intensities that are routinely produced at LCLS take place at the Coherent X
      ray Imaging (CXI) instrument, which can produce spotsize at the order of 100 nm,
      and such spotsizes and intensities are crucial for experiments ranging from
      coherent diffractive imaging, non-linear x-ray optics and high field physics, and
      single molecule imaging. Nevertheless, a full characterisation of this beam has
      up to now not been performed. In this paper we for the first time characterise
      this nanofocused beam in both phase and intensity using a Ronchi Shearing
      Interferometric technique. The method is fast, in-situ, uses a straightforward
      optimization algoritm, and is insensitive to spatial jitter.

PMID- 29057939
TI  - Prognostic values of red blood cell distribution width, platelet count, and red
      cell distribution width-to-platelet ratio for severe burn injury.
AB  - Red blood cell distribution width (RDW), platelet count (PLT), and a RDW-to-PLT
      ratio (RPR) have been associated with inflammatory activity and adverse outcomes
      in many diseases. This study has aimed to investigate the association between
      these indicators and the mortality rate of severe burn patients. From 2008 to
      2014, 610 cases of severe burn patients from two burn centers in eastern China
      were enrolled in this study. Eighty-eight patients died within 90 days after
      admission. The RDW, PLT, and RPR were studied through Cox regression analysis on
      the 3rd and 7th day. The RDW, PLT, and RPR values on the 3rd and 7th day were
      significantly associated with the outcomes of severe burn patients (P < 0.01).
      High RPR was significantly associated with a 90-day mortality rate at the two
      time points. However, the RDW and PLT did not provide independent predictive
      values. Our results indicated that the RPR values on the 3rd and 7th day were
      associated with the mortality rates of severe burn patients (P < 0.01).
      Meanwhile, the RDW and PLT values at these time points failed to provide
      independent values for burn mortality prediction. Thus, the RPR can serve as an
      independent and novel marker for mortality rates prediction in severe burn
      patients.

PMID- 29057940
TI  - Water conservation benefits of urban heat mitigation.
AB  - Many cities globally are seeking strategies to counter the consequences of both a
      hotter and drier climate. While urban heat mitigation strategies have been shown
      to have beneficial effects on health, energy consumption, and greenhouse gas
      emissions, their implications for water conservation have not been widely
      examined. Here we use a suite of satellite-supported regional climate simulations
      in California to show that broad implementation of cool roofs, a heat mitigation
      strategy, not only results in significant cooling, but can also meaningfully
      decrease outdoor water consumption by reducing evaporative and irrigation water
      demands. Irrigation water consumption across the major metropolitan areas is
      reduced by up to 9% and irrigation water savings per capita range from 1.8 to
      15.4 gallons per day across 18 counties examined. Total water savings are found
      to be the highest in Los Angeles county, reaching about 83 million gallons per
      day. Cool roofs are a valuable solution for addressing the adaptation and
      mitigation challenges faced by multiple sectors in California.

PMID- 29057941
TI  - Cyclobutane-1,3-Diacid (CBDA): A Semi-Rigid Building Block Prepared by [2+2]
      Photocyclization for Polymeric Materials.
AB  - A previously overlooked building block, cyclobutane-1,3-diacid (CBDA), is
      introduced to materials synthesis due to its great potentials. As an example of
      CBDA, alpha-truxillic acid or 2,4-diphenylcyclobutane-1,3-dicarboxylic acid, was
      readily synthesized from commercially available trans-cinnamic acid. This CBDA
      showed outstanding stability both in sunlight and upon heating. While its two
      carboxylic acid groups can be readily utilized in connecting with other molecules
      to form new materials, the cyclobutane ring was able to tolerate acid and base
      treatments showing good chemical stability. A series of cyclobutane-containing
      polymers (CBPs), namely poly-alpha-truxillates, were obtained by condensation
      between alpha-truxillic acid and diols including ethylene glycol, 1,3
      propanediol, 1,4-butanediol, 1,5-petanediol, and 1,6-hexanediol. The structures
      of these poly-alpha-truxillates were analyzed by NMR, FT-IR, and HRMS. Powder X
      ray diffraction results of the poly-alpha-truxillates indicated that they are
      semi-crystalline materials. Preliminary thermal, chemical, and photochemical
      tests showed that the poly-alpha-truxillates exhibited comparable stabilities to
      PET.

PMID- 29057942
TI  - Functional and Structural Studies of a Multidomain Alginate Lyase from
      Persicobacter sp. CCB-QB2.
AB  - AlyQ from Persicobacter sp. CCB-QB2 is an alginate lyase with three domains - a
      carbohydrate-binding domain modestly resembling family 16 carbohydrate-binding
      module (CBM16), a family 32 CBM (CBM32) domain, and an alginate lyase domain
      belonging to polysaccharide lyase family 7 (PL7). Although AlyQ can also act on
      polyguluronate (poly-G) and polymannuronate (poly-M), it is most active on
      alginate. Studies with truncated AlyQ showed that the CBM32 domain did not
      contribute to enhancing AlyQ's activity under the assayed conditions.
      Nevertheless, it could bind to cleaved but not intact alginate, indicating that
      the CBM32 domain recognises alginate termini. The crystal structure containing
      both CBM32 and catalytic domains show that they do not interact with one another.
      The CBM32 domain contains a conserved Arg that may bind to the carboxyl group of
      alginate. The catalytic domain, meanwhile, shares a conserved substrate-binding
      groove, and the presence of two negatively charged Asp residues may dictate
      substrate specificity especially at subsite +1. As Persicobacter sp. CCB-QB2 was
      unable to utilise alginate, AlyQ may function to help the bacterium degrade cell
      walls more efficiently.

PMID- 29057943
TI  - High-Fat Diet-Induced Insulin Resistance in Single Skeletal Muscle Fibers is
      Fiber Type Selective.
AB  - Skeletal muscle is the major site for insulin-stimulated glucose disposal, and
      muscle insulin resistance confers many negative health outcomes. Muscle is
      composed of multiple fiber types, and conventional analysis of whole muscles
      cannot elucidate fiber type differences at the cellular level. Previous research
      demonstrated that a brief (two weeks) high fat diet (HFD) caused insulin
      resistance in rat skeletal muscle. The primary aim of this study was to determine
      in rat skeletal muscle the influence of a brief (two weeks) HFD on glucose uptake
      (GU) +/- insulin in single fibers that were also characterized for fiber type.
      Epitrochlearis muscles were incubated with [3H]-2-deoxyglucose (2DG) +/- 100
      uU/ml insulin. Fiber type (myosin heavy chain expression) and 2DG accumulation
      were measured in whole muscles and single fibers. Although fiber type composition
      of whole muscles did not differ between diet groups, GU of insulin-stimulated
      whole muscles from LFD rats significantly exceeded HFD values (P < 0.005). For
      HFD versus LFD rats, GU of insulin-stimulated single fibers was significantly (P
      < 0.05) lower for IIA, IIAX, IIBX, IIB, and approached significance for IIX (P =
      0.100), but not type I (P = 0.776) fibers. These results revealed HFD-induced
      insulin resistance was attributable to fiber type selective insulin resistance
      and independent of altered fiber type composition.

PMID- 29057944
TI  - Linked magnolol dimer as a selective PPARgamma agonist - Structure-based rational
      design, synthesis, and bioactivity evaluation.
AB  - The nuclear receptors peroxisome proliferator-activated receptor gamma
      (PPARgamma) and its hetero-dimerization partner retinoid X receptor alpha
      (RXRalpha) are considered as drug targets in the treatment of diseases like the
      metabolic syndrome and diabetes mellitus type 2. Effort has been made to develop
      new agonists for PPARgamma to obtain ligands with more favorable properties than
      currently used drugs. Magnolol was previously described as dual agonist of
      PPARgamma and RXRalpha. Here we show the structure-based rational design of a
      linked magnolol dimer within the ligand binding domain of PPARgamma and its
      synthesis. Furthermore, we evaluated its binding properties and functionality as
      a PPARgamma agonist in vitro with the purified PPARgamma ligand binding domain
      (LBD) and in a cell-based nuclear receptor transactivation model in HEK293 cells.
      We determined the synthesized magnolol dimer to bind with much higher affinity to
      the purified PPARgamma ligand binding domain than magnolol (K i values of 5.03
      and 64.42 nM, respectively). Regarding their potency to transactivate a PPARgamma
      dependent luciferase gene both compounds were equally effective. This is likely
      due to the PPARgamma specificity of the newly designed magnolol dimer and lack of
      RXRalpha-driven transactivation activity by this dimeric compound.

PMID- 29057945
TI  - A pilot evaluation of whole blood finger-prick sampling for point-of-care HIV
      viral load measurement: the UNICORN study.
AB  - There is a global need for HIV viral load point-of-care (PoC) assays to monitor
      patients receiving antiretroviral therapy. UNICORN was the first study of an off
      label protocol using whole blood finger-prick samples tested with and without a
      simple three minute spin using a clinic-room microcentrifuge. Two PoC assays were
      evaluated in 40 HIV-positive participants, 20 with detectable and 20 with
      undetectable plasma viral load (pVL) (<20 copies/ml). Using 100 ul finger-prick
      blood samples, the Cepheid Xpert HIV-1 Viral Load and HIV-1 Qual cartridges were
      compared with laboratory pVL assessment (TaqMan, Roche). For participants with
      undetectable viraemia by TaqMan, there was poor concordance without
      centrifugation with the TaqMan platform with only 40% 'undetectable' using Xpert
      VL and 25% 'not detected' using the Qual assay. After a 3 minute spin, 100% of
      samples were undetectable using either assay, showing full concordance with the
      TaqMan assay. Defining a lower limit of detection of 1000 copies/ml when
      including a spin, there was 100% concordance with the TaqMan platform with strong
      correlation (rho 0.95 and 0.94; p < 0.0001 for both assays). When including a
      simple microcentrifugation step, finger-prick PoC testing was a quick and
      accurate approach for assessing HIV viraemia, with excellent concordance with
      validated laboratory approaches.

PMID- 29057946
TI  - Resilience and regime shifts in a marine biodiversity hotspot.
AB  - Complex natural systems, spanning from individuals and populations to ecosystems
      and social-ecological systems, often exhibit abrupt reorganizations in response
      to changing stressors, known as regime shifts or critical transitions. Theory
      suggests that such systems feature folded stability landscapes with fluctuating
      resilience, fold-bifurcations, and alternate basins of attraction. However, the
      implementation of such features to elucidate response mechanisms in an empirical
      context is scarce, due to the lack of generic approaches to quantify resilience
      dynamics in individual natural systems. Here, we introduce an Integrated
      Resilience Assessment (IRA) framework: a three-step analytical process to assess
      resilience and construct stability landscapes of empirical systems. The proposed
      framework involves a multivariate analysis to estimate holistic system indicator
      variables, non-additive modelling to estimate alternate attractors, and a
      quantitative resilience assessment to scale stability landscapes. We implement
      this framework to investigate the temporal development of the Mediterranean
      marine communities in response to sea warming during 1985-2013, using fisheries
      landings data. Our analysis revealed a nonlinear tropicalisation of the
      Mediterranean Sea, expressed as abrupt shifts to regimes dominated by
      thermophilic species. The approach exemplified here for the Mediterranean Sea,
      revealing previously unknown resilience dynamics driven by climate forcing, can
      elucidate resilience and shifts in other complex systems.

PMID- 29057947
TI  - Reconstruction of Toll-like receptor 9-mediated responses in HEK-Blue hTLR9 cells
      by transfection of human macrophage scavenger receptor 1 gene.
AB  - We used human Toll-like receptor 9 (hTLR9)-expressing HEK-Blue hTLR9 cells, which
      release secreted embryonic alkaline phosphatase (SEAP) upon response to CpG DNA,
      to evaluate the immunological properties of nucleic acid drug candidates. Our
      preliminary studies showed that phosphodiester CpG DNA hardly induced any SEAP
      secretion in HEK-Blue hTLR9 cells. In the current study, therefore, we developed
      HEK-Blue hTLR9 cells transduced with human macrophage scavenger receptor-1
      (hMSR1), a cell-surface DNA receptor, and determined whether HEK-Blue hTLR9/hMSR1
      cells respond to phosphorothioate (PS) CpG DNA and phosphodiester (PO) CpG DNA.
      We selected PS CpG2006, a single-stranded PO CpG DNA (ssCpG), and a tetrapod-like
      structured DNA (tetrapodna) containing ssCpG (tetraCpG) as model TLR9 ligands.
      Alexa Fluor 488-labeled ligands were used for flow cytometry. Unlike the mock
      transfected HEK-Blue hTLR9 cells, the HEK-Blue hTLR9/hMSR1 cells efficiently took
      up all three CpG DNAs. SEAP release was almost proportional to the uptake.
      Treatment of HEK-Blue hTLR9/hMSR1 cells with an anti-hMSR1 antibody significantly
      reduced the uptake of ssCpG and tetraCpG. Collectively, reconstruction of TLR9
      mediated responses to CpG DNA in HEK-Blue hTLR9 cells can be used to evaluate the
      toxicity of nucleic acid drug candidates with diverse physicochemical properties.

PMID- 29057948
TI  - Main factor causing "faster-is-slower" phenomenon during evacuation: rodent
      experiment and simulation.
AB  - Understanding crowd flow at bottlenecks is important for preventing accidents in
      emergencies. In this research, a crowd evacuation passing through a narrow exit
      connected with guide-walls is analysed using the discrete element method based on
      physical and psychological modelling in parallel with empirical rodent research.
      Results of rodent experiment and simulation demonstrate the faster-is-slower
      (FIS) effect, which is a well-known phenomenon in pedestrian dynamics. As the
      angle of the guide-walls increases, agents rapidly evacuate the room even though
      they have low velocity. The increase in this angle causes agents to form lanes.
      It is validated that ordered agents evacuate expeditiously with relatively low
      velocity despite expectations to the contrary. The extracted experimental and
      simulation data strongly suggest that the agents' standard deviation of velocity
      can be a key factor causing the FIS effect. It is found that the FIS effect can
      be eliminated by controlling the standard deviation.

PMID- 29057949
TI  - Immunosenescence patterns differ between populations but not between sexes in a
      long-lived mammal.
AB  - In animals, physiological mechanisms underlying reproductive and actuarial
      senescence remain poorly understood. Immunosenescence, the decline in the ability
      to display an efficient immune response with increasing age, is likely to
      influence both reproductive and actuarial senescence through increased risk of
      disease. Evidence for such a link has been reported from laboratory animal models
      but has been poorly investigated in the wild, where variation in resource
      acquisitions usually drives life-history trade-offs. We investigated
      immunosenescence patterns over 7 years in both sexes of two contrasting roe deer
      populations (Capreolus capreolus). We first measured twelve immune markers to
      obtain a thorough identification of innate and adaptive components of immunity
      and assessed, from the same individuals, the age-dependent variation observed in
      parasitic infections. Although the level of innate traits was maintained at old
      age, the functional innate immune traits declined with increasing age in one of
      two populations. In both populations, the production of inflammatory markers
      increased with advancing age. Finally, the adaptive response declined in late
      adulthood. The increasing parasite burden with age we reported suggests the
      effective existence of immunosenescence. Age-specific patterns differed between
      populations but not between sexes, which indicate that habitat quality could
      shape age-dependent immune phenotype in the wild.

PMID- 29057950
TI  - Energetic mitochondrial failing in vitiligo and possible rescue by cardiolipin.
AB  - Vitiligo is characterized by death or functional defects of epidermal melanocytes
      through still controversial pathogenic process. Previously, we showed that
      mitochondria-driven pre-senescent phenotype diminishes the capability of vitiligo
      melanocytes to cope with stressful stimuli. In the current study, we investigated
      markers of mitochondrial energy metabolism including the PGC1a axis, and then we
      determined the index of mitochondrial impairment using a cytomic approach. We
      found in cultured epidermal vitiligo melanocytes, compared to healthy ones, low
      ATP, increased proton leakage, and altered expression of several glycolytic
      enzymes (hexokinase II, pyruvic dehydrogenase kinase 1 and pyruvic kinase M2), We
      suggest that the low ATP production may be sufficient in steady-state conditions
      but it is unable to cover further needs. We also found in vitiligo melanocyrtes
      hyper-activation of the PGC1alpha axis, finalized to counteract the energy
      defect. Cytomic analysis, supported by MitoTracker Red pattern and ex-vivo
      immunohistochemistry, suggested an increased mitochondrial mass, possibly useful
      to ensure the essential ATP level. Finally, pharmacological cardiolipin
      stabilization reverted the energetic impairment, confirming the initial
      mitochondrial role. In conclusion, we report new insight in the pathogenetic
      mechanism of viitligo and indicate that the mitochondrial failure rescue by
      cardiolipin manipulation may be a new intriguing target in treatment development.

PMID- 29057951
TI  - Preconditioning with far-infrared irradiation enhances proliferation, cell
      survival, and migration of rat bone marrow-derived stem cells via CXCR4-ERK
      pathways.
AB  - Far-infrared radiation (FIR) has been shown to exert positive effects on the
      cardiovascular system. However, the biological effects of FIR on bone marrow
      derived stem cells (BMSCs) are not understood. In the present study, BMSCs were
      isolated from rat femur bone marrow and cultured in vitro. To investigate the
      effects of an FIR generator with an energy flux of 0.13 mW/cm2 on rat BMSCs,
      survival of BMSCs was measured by crystal violet staining, and cell proliferation
      was additionally measured using Ez-Cytox cell viability, EdU, and Brd U assays.
      FIR preconditioning was found to significantly increase BMSC proliferation and
      survival against H2O2. The scratch and transwell migration assays showed that FIR
      preconditioning resulted in an increase in BMSC migration. qRT-PCR and Western
      blot analyses demonstrated that FIR upregulated Nanog, Sox2, c-Kit, Nkx2.5, and
      CXCR4 at both the mRNA and protein levels. Consistent with these observations,
      PD98059 (an ERK inhibitor) and AMD3100 (a CXCR4 inhibitor) prevented the
      activation of CXCR4/ERK and blocked the cell proliferation and migration induced
      by FIR. Overall, these findings provide the first evidence that FIR confers a
      real and significant benefit on the preconditioning of BMSCs, and might lead to
      novel strategies for improving BMSC therapy for cardiac ischemia.

PMID- 29057952
TI  - Identification of differentially expressed circular RNAs in human monocyte
      derived macrophages response to Mycobacterium tuberculosis infection.
AB  - Macrophages act as the first line of host immune defense against Mycobacterium
      tuberculosis (Mtb). Recent studies have demonstrated circular RNAs (circRNAs) are
      implicated in a variety of physiological and pathological processes; however, the
      role of circRNAs in macrophages response to Mtb infection remain unknown. To
      address this issue, here we characterized circRNAs expression profiles in human
      monocyte derived macrophages (MDMs) response to Mtb infection using microarray
      assay. Our results revealed that many circRNAs were differentially expressed in
      human MDMs after Mtb infection; of these, 32 circRNAs were up-regulated and 110
      were down-regulated. Real time PCR results were generally consistent with the
      microarray data. Furthermore, we found that hsa_circ_0043497 and hsa_circ_0001204
      may be effective diagnostic biomarkers for TB. This study provides the first
      evidence that circRNAs alterations are involved in human MDMs response to TB
      infection and reveal potential targets for diagnostics and the treatment of TB.

PMID- 29057953
TI  - Structural and electronic determinants of lytic polysaccharide monooxygenase
      reactivity on polysaccharide substrates.
AB  - Lytic polysaccharide monooxygenases (LPMOs) are industrially important copper
      dependent enzymes that oxidatively cleave polysaccharides. Here we present a
      functional and structural characterization of two closely related AA9-family
      LPMOs from Lentinus similis (LsAA9A) and Collariella virescens (CvAA9A). LsAA9A
      and CvAA9A cleave a range of polysaccharides, including cellulose, xyloglucan,
      mixed-linkage glucan and glucomannan. LsAA9A additionally cleaves isolated xylan
      substrates. The structures of CvAA9A and of LsAA9A bound to cellulosic and non
      cellulosic oligosaccharides provide insight into the molecular determinants of
      their specificity. Spectroscopic measurements reveal differences in copper co
      ordination upon the binding of xylan and glucans. LsAA9A activity is less
      sensitive to the reducing agent potential when cleaving xylan, suggesting that
      distinct catalytic mechanisms exist for xylan and glucan cleavage. Overall, these
      data show that AA9 LPMOs can display different apparent substrate specificities
      dependent upon both productive protein-carbohydrate interactions across a binding
      surface and also electronic considerations at the copper active site.

PMID- 29057954
TI  - Photosensing and Thermosensing by Phytochrome B Require Both Proximal and Distal
      Allosteric Features within the Dimeric Photoreceptor.
AB  - Phytochromes (Phys) encompass a diverse collection of bilin-containing
      photoreceptors that help plants and microorganisms perceive light through
      photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing
      states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic
      process that enables temperature sensation in plants and possibly other
      organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled
      recombinantly, coupled with measurements of solution size, photoconversion, and
      thermal reversion, we identified both proximal and distal features that influence
      all three metrics. Included are the downstream C-terminal histidine kinase
      related domain known to promote dimerization and a conserved patch just upstream
      of an N-terminal Period/Arnt/Sim (PAS) domain, which upon removal dramatically
      accelerates thermal reversion. We also discovered that the nature of the bilin
      strongly influences Pfr stability. Whereas incorporation of the native bilin
      phytochromobilin into PhyB confers robust Pfr -> Pr thermal reversion, that
      assembled with the cyanobacterial version phycocyanobilin, often used for
      optogenetics, has a dramatically stabilized Pfr state. Taken together, we
      conclude that Pfr acquisition and stability are impacted by a collection of
      opposing allosteric features that inhibit or promote photoconversion and
      reversion of Pfr back to Pr, thus allowing Phys to dynamically measure light,
      temperature, and possibly time.

PMID- 29057955
TI  - Investigation of Melts of Polybutylcarbosilane Dendrimers by 1H NMR Spectroscopy.
AB  - Melts of polybutylcarbosilane (PBC) dendrimers from third (G3) up to sixth (G6)
      generations are investigated by 1H NMR spectroscopy in a wide temperature range
      up to 493 K. At room temperature, NMR spectra of G3-G5 dendrimers exhibit
      resolved, solution-like spectra ("liquid" phase). In contrast, the spectrum of
      the G6 dendrimer is characterized by a single unresolved broad line at whole
      temperature range, which supports the presence of an anomalous phase state of G6
      at temperatures higher than glass transition temperature. For the first time, an
      unexpected transition of G5 dendrimer from a molecular liquid state to an
      anomalous state/phase upon temperature increase has been detected using NMR data.
      Specifically, an additional wide background line appears in the G5 spectrum above
      473 K, and this line corresponds to a G5 state characterized by restricted
      molecular mobility, i.e., a state similar to the "anomalous" phase of G6 melt.
      The fraction of the G5 dendrimers in "anomalous" phase at 493 K is approximately
      40%. Analysis of the spectral shapes suggests that changes in the G5 dendrimers
      are reversible with temperature.

PMID- 29057956
TI  - A mammalian blood odor component serves as an approach-avoidance cue across
      phylum border - from flies to humans.
AB  - Chemosignals are used by predators to localize prey and by prey to avoid
      predators. These cues vary between species, but the odor of blood seems to be an
      exception and suggests the presence of an evolutionarily conserved chemosensory
      cue within the blood odor mixture. A blood odor component, E2D, has been shown to
      trigger approach responses identical to those triggered by the full blood odor in
      mammalian carnivores and as such, is a key candidate as a food/alarm cue in
      blood. Using a multidisciplinary approach, we demonstrate that E2D holds the dual
      function of affecting both approach and avoidance behavior in a predator-prey
      predicted manner. E2D evokes approach responses in two taxonomically distant
      blood-seeking predators, Stable fly and Wolf, while evoking avoidance responses
      in the prey species Mouse. We extend this by demonstrating that this chemical cue
      is preserved in humans as well; E2D induces postural avoidance, increases
      physiological arousal, and enhances visual perception of affective stimuli. This
      is the first demonstration of a single chemical cue with the dual function of
      guiding both approach and avoidance in a predator-prey predicted manner across
      taxonomically distant species, as well as the first known chemosignal that
      affects both human and non-human animals alike.

PMID- 29057957
TI  - Bottom-up precise synthesis of stable platinum dimers on graphene.
AB  - Supported metal clusters containing only a few atoms are of great interest.
      Progress has been made in synthesis of metal single-atom catalysts. However,
      precise synthesis of metal dimers on high-surface area support remains a grand
      challenge. Here, we show that Pt2 dimers can be fabricated with a bottom-up
      approach on graphene using atomic layer deposition, through proper nucleation
      sites creation, Pt1 single-atom deposition and attaching a secondary Pt atom
      selectively on the preliminary one. Scanning transmission electron microscopy, x
      ray absorption spectroscopy, and theoretical calculations suggest that the Pt2
      dimers are likely in the oxidized form of Pt2Ox. In hydrolytic dehydrogenation of
      ammonia borane, Pt2 dimers exhibit a high specific rate of 2800 molH2 molPt-1 min
      1 at room temperature, ~17- and 45-fold higher than graphene supported Pt single
      atoms and nanoparticles, respectively. These findings open an avenue to bottom-up
      fabrication of supported atomically precise ultrafine metal clusters for
      practical applications.

PMID- 29057958
TI  - Evolving stability and pH-dependent activity of the high redox potential Botrytis
      aclada laccase for enzymatic fuel cells.
AB  - Fungal high redox potential laccases are proposed as cathodic biocatalysts in
      implantable enzymatic fuel cells to generate high cell voltages. Their
      application is limited mainly through their acidic pH optimum and chloride
      inhibition. This work investigates evolutionary and engineering strategies to
      increase the pH optimum of a chloride-tolerant, high redox potential laccase from
      the ascomycete Botrytis aclada. The laccase was subjected to two rounds of
      directed evolution and the clones screened for increased stability and activity
      at pH 6.5. Beneficial mutation sites were investigated by semi-rational and
      combinatorial mutagenesis. Fourteen variants were characterised in detail to
      evaluate changes of the kinetic constants. Mutations increasing thermostability
      were distributed over the entire structure. Among them, T383I showed a 2.6-fold
      increased half-life by preventing the loss of the T2 copper through unfolding of
      a loop. Mutations affecting the pH-dependence cluster around the T1 copper and
      categorise in three types of altered pH profiles: pH-type I changes the monotonic
      decreasing pH profile into a bell-shaped profile, pH-type II describes increased
      specific activity below pH 6.5, and pH-type III increased specific activity above
      pH 6.5. Specific activities of the best variants were up to 5-fold higher (13 U
      mg-1) than BaL WT at pH 7.5.

PMID- 29057959
TI  - Challenging FRET-based E-Cadherin force measurements in Drosophila.
AB  - Mechanical forces play a critical role during embryonic development. Cellular and
      tissue wide forces direct cell migration, drive tissue morphogenesis and regulate
      organ growth. Despite the relevance of mechanics for these processes, our
      knowledge of the dynamics of mechanical forces in living tissues remains scarce.
      Recent studies have tried to address this problem with the development of tension
      sensors based on Forster resonance energy transfer (FRET). These sensors are
      integrated into force bearing proteins and allow the measurement of mechanical
      tensions on subcellular structures. Here, we developed such a FRET-based sensor
      to measure E-Cadherin tensions in different Drosophila tissues in and ex vivo.
      Similar to previous studies, we integrated the sensor module into E-cadherin. We
      assessed the sensitivity of the sensor by measuring dynamic, developmental
      processes and mechanical modifications in three Drosophila tissues: the wing
      imaginal disc, the amnioserosa cells and the migrating border cells. However,
      these assays revealed that the sensor is not functional to measure the magnitude
      of tensions occurring in any of the three tissues. Moreover, we encountered
      technical problems with the measurement of FRET, which might represent more
      general pitfalls with FRET sensors in living tissues. These insights will help
      future studies to better design and control mechano-sensing experiments.

PMID- 29057960
TI  - Contrasting glacier responses to recent climate change in high-mountain Asia.
AB  - Recent studies of Asian glaciers have shown that glaciers in eastern Karakoram
      and West Kunlun have been slightly gaining mass while those in nearby Jammu
      Kashmir and Himalayas are losing mass, at rates of more than 0.5 m w.e.yr-1 and
      about 0.3 m w.e.yr-1, respectively. Two possible explanations have been proposed
      for this difference in glacier behaviour: spatial heterogeneity in climate change
      (climatic forcing) or differing glacier responses to climate change (glacier
      response). However, neither explanation has strong supporting evidence. Here, we
      examine the glacial response by calculating the mass-balance sensitivity to
      temperature change in high-mountain Asia. In support of the glacier-response
      explanation, we find a strong correlation between observed glacier surface
      elevation changes and mass-balance sensitivity of glaciers. The high coefficient
      of determination (R2 = 0.61) suggests that spatially heterogeneous mass-balance
      sensitivity has more explanatory power than regionally different climate change
      for the recent contrasting glacier fluctuations in the high mountain Asia.

PMID- 29057963
TI  - Impact of analytical and biological variations on classification of diabetes
      using fasting plasma glucose, oral glucose tolerance test and HbA1c.
AB  - Historically, diabetes is diagnosed by measuring fasting (FPG) and two-hour post
      oral glucose load (OGTT) plasma concentration and interpreting it against
      recommended clinical thresholds of the patient. More recently, glycated
      haemoglobin A1c (HbA1c) has been included as a diagnostic criterion. Within
      individual biological variation (CVi), analytical variation (CVa) and analytical
      bias of a test can impact on the accuracy and reproducibility of the
      classification of a disease. A test with large biological and analytical
      variation increases the likelihood of erroneous classification of the underlying
      disease state of a patient. Through numerical simulations based on the laboratory
      results generated from a large population health survey, we examined the impact
      of CVi, CVa and bias on the classification of diabetes using fasting plasma
      glucose (FPG), oral glucose tolerance test (OGTT) and HbA1c. From the results of
      the simulations, HbA1c has comparable performance to FPG and is better than OGTT
      in classifying subjects with diabetes, particularly when laboratory methods with
      smaller CVa are used. The use of the average of the results of the repeat
      laboratory tests has the effect of ameliorating the combined (analytical and
      biological) variation. The averaged result improves the consistency of the
      disease classification.

PMID- 29057961
TI  - Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis.
AB  - Extracellular ATP is a central signaling molecule in inflammatory responses.
      Pannexin1 (Panx1) channels release ATP in a controlled manner and have been
      implicated in various inflammatory pathologies, but their role in atherogenesis
      remains elusive. Using atherosclerosis-susceptible mouse models with ubiquitous
      deletion of Panx1 (Panx1 -/- Apoe -/- ) or with Cre recombinase-mediated deletion
      of Panx1 in endothelial cells and monocytes (Tie2-Cre Tg Panx1 fl/fl Apoe -/- ;
      Panx1 del Apoe -/- ), we identified a novel role for Panx1 in the lymphatic
      vasculature. Atherosclerotic lesion development in response to high-cholesterol
      diet was enhanced in Panx1 del Apoe -/- mice, pointing to an atheroprotective
      role for Panx1 in endothelial and/or monocytic cells. Unexpectedly, atherogenesis
      was not changed in mice with ubiquitous Panx1 deletion, but Panx1 -/- Apoe -/-
      mice displayed reduced body weight, serum cholesterol, triglycerides and free
      fatty acids, suggesting altered lipid metabolism in these Panx1-deficient mice.
      Mechanistically, Panx1 -/- Apoe -/- mice showed impairment of lymphatic vessel
      function with decreased drainage of interstitial fluids and reduced dietary fat
      absorption. Thus, the detrimental effect of Panx1 deletion in endothelial and/or
      monocytic cells during atherogenesis is counterbalanced by an opposite effect
      resulting from impaired lymphatic function in ubiquitous Panx1-deficient mice.
      Collectively, our findings unveil a pivotal role of Panx1 in linking lymphatic
      function to lipid metabolism and atherosclerotic plaque development.

PMID- 29057962
TI  - TNFR1 inhibition with a Nanobody protects against EAE development in mice.
AB  - TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF
      medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2
      signaling reduces the pro-inflammatory effects of TNF but preserves the important
      neuroprotective signals via TNFR2. We previously reported the generation of a
      Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in
      experimental autoimmune encephalomyelitis (EAE). We specifically antagonized
      TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG35-55-induced
      EAE. Because TROS does not cross-react with mouse TNFR1, we generated mice
      expressing human TNFR1 in a mouse TNFR1-knockout background (hTNFR1 Tg), and we
      determined biodistribution of 99mTc-TROS and effectiveness of TROS in EAE in
      those mice. Biodistribution analysis demonstrated that intraperitoneally injected
      TROS is retained more in organs of hTNFR1 Tg mice compared to wild type mice.
      TROS was also detected in the cerebrospinal fluid (CSF) of hTNFR1 Tg mice.
      Prophylactic TROS administration significantly delayed disease onset and
      ameliorated its symptoms. Moreover, treatment initiated early after disease onset
      prevented further disease development. TROS reduced spinal cord inflammation and
      neuroinflammation, and preserved myelin and neurons. Collectively, our data
      illustrate that TNFR1 is a promising therapeutic target in MS.

PMID- 29057964
TI  - HIV-1 sequences in the epidemic suggest an alternative pathway for the generation
      of the Long Terminal Repeats.
AB  - To generate the long-terminal repeats (LTR) that border the integrated viral
      genome, two-strand transfer steps must occur during reverse transcription.
      Analysis of the genetic polymorphisms that are present in the LTR of HIV-1
      heterozygous virions in single infection cycle studies has revealed which of the
      two copies of genomic RNAs is used for each transfer event. Thus, the first event
      of strand transfer has been described to be either intra- or intermolecular,
      while the second event is generally intramolecular. Here, we repeated these
      analyses using sequences from HIV databases and extended the study to the regions
      surrounding the LTR. We observed a striking correlation between the pattern of
      recombination in the LTR and the phylogenetic origin of the surrounding
      sequences. This correlation suggests that the second-strand transfer can be
      either intra- or intermolecular and, interestingly, could reflect an effect of
      proximity between nucleic acids that would guide this transfer. This factor could
      be particularly relevant for heterozygous viruses containing highly divergent
      genomic RNAs, such as those considered in the present study.

PMID- 29057965
TI  - A minimalistic and optimized conveyor belt for neutral atoms.
AB  - Here we report of a design and the performance of an optimized micro-fabricated
      conveyor belt for precise and adiabatic transportation of cold atoms. A
      theoretical model is presented to determine optimal currents in conductors used
      for the transportation. We experimentally demonstrate a fast adiabatic
      transportation of Rubidium (87Rb) cold atoms with minimal loss and heating with
      as few as three conveyor belt conductors. This novel design of a multilayered
      conveyor belt structure is fabricated in aluminium nitride (AlN) because of its
      outstanding thermal and electrical properties. This demonstration would pave a
      way for a compact and portable quantum device required for quantum information
      processing and sensors, where precise positioning of cold atoms is desirable.

PMID- 29057966
TI  - MKL1 expressed in macrophages contributes to the development of murine colitis.
AB  - Mice deficient in the megakaryoblastic leukaemia 1 (Mkl1) gene experience less
      severe dextran sulphate sodium (DSS)-induced colitis, implying that Mkl1 plays a
      pathological role in inflammatory bowel disease (IBD). However, the contribution
      of Mkl1 to the development of colitis remains to be elucidated. The expression of
      Mkl1 is higher in the colonic lamina propria macrophages (LPMac) of DSS-treated
      mice than in those of control mice. Therefore, we established a transgenic mouse
      line that overexpresses human MKL1 (MKL1-Tg) specifically in cells of the
      monocyte/macrophage lineage, in order to investigate the potential role of
      macrophage MKL1 in the pathogenesis of colitis. MKL1-Tg mice displayed
      spontaneous colon shortening and rectal prolapse. Flow cytometric and
      quantitative RT-PCR analyses revealed that, in MKL1-Tg mice compared to
      littermate controls, the population of LPMac was decreased and had an altered
      inflammatory phenotype indicative of impaired anti-inflammatory properties,
      whereas bone marrow-derived macrophages from MKL1-Tg mice skewed towards M1
      polarisation. In addition, MKL1-Tg mice had higher susceptibility to DSS-induced
      colitis than their littermate controls. These observations indicated that MKL1
      crucially contributes to the development of colitis via the regulation of the
      function of macrophages, suggesting that it may be a potential therapeutic target
      for the prevention of IBD.

PMID- 29057968
TI  - Mid-troposphere transport of Middle-East dust over the Arabian Sea and its effect
      on rainwater composition and sensitive ecosystems over India.
AB  - The importance of mineral dust and aerosols in the transfer of bio-essential
      elements to terrestrial and marine ecosystems far removed from the source region
      is well known. Aerosol concentrations measured at the surface over the west coast
      of India during the SW monsoon period (June to September) are usually very low as
      pristine maritime air from the Southern Indian Ocean blows over this region.
      However, we find very high levels of mineral dust and dust derived nutrients in
      rainwater collected during the SW monsoon period. We show that the dry, warm and
      dusty Red Sea Wind and Shamal Wind from the Middle-East override the moist
      oceanic Low-Level Jet (Findlater Jet) of the SW monsoon and transport large
      quantities of dust at heights between 2 km and 5 km over the Indian Peninsula. A
      substantial portion is the desert dust is scavenged and wet-deposited over the
      Western Ghats of India where it neutralizes the acidity of rainwater and provides
      substantial amounts of nutrients that have the potential to impact sensitive
      ecosystems in this region. After the Red Sea and Shamal Winds subside in
      September, the alkaline rainwater reverts to the acidic range due to soluble ions
      derived from local carbonaceous aerosols.

PMID- 29057967
TI  - Helicobacter pylori gamma-glutamyl transferase contributes to colonization and
      differential recruitment of T cells during persistence.
AB  - Helicobacter pylori gamma-glutamyl transferase (gGT) is a key bacterial virulence
      factor that is not only important for bacterial gastric colonization but also
      related to the development of gastric pathology. Despite accumulating evidence
      for pathogenic and immunologic functions of H. pylori gGT, it is still unclear
      how it supports gastric colonization and how its specific effects on the host's
      innate and adaptive immune responses contribute to colonization and pathology. We
      have compared mice showing similar bacterial load after infection with gGT
      proficient or gGT-deficient H. pylori to analyse the specific role of the enzyme
      during infection. Our data indicate that H. pylori gGT supports initial
      colonization. Nevertheless, bacteria lacking gGT can still colonize and persist.
      We observed that the presence of gGT during infection favoured a proinflammatory
      innate and adaptive immune response. Notably, H. pylori gGT activity was linked
      to increased levels of IFNgamma, which were attributed to a differential
      recruitment of CD8+ T cells to the stomach. Our data support an essential role
      for H. pylori gGT in gastric colonization and further suggest that gGT favours
      infiltration of CD8+ cells to the gastric mucosa, which might play an important
      and yet overlooked role in the pathogenesis of H. pylori.

PMID- 29057969
TI  - Controlling the Overfitting of Heritability in Genomic Selection through Cross
      Validation.
AB  - In genomic selection (GS), all the markers across the entire genome are used to
      conduct marker-assisted selection such that each quantitative trait locus of
      complex trait is in linkage disequilibrium with at least one marker. Although GS
      improves estimated breeding values and genetic gain, in most GS models genetic
      variance is estimated from training samples with many trait-irrelevant markers,
      which leads to severe overfitting in the calculation of trait heritability. In
      this study, we demonstrated overfitting heritability due to the inclusion of
      trait-irrelevant markers using a series of simulations, and such overfitting can
      be effectively controlled by cross validation experiment. In the proposed method,
      the genetic variance is simply the variance of the genetic values predicted
      through cross validation, the residual variance is the variance of the
      differences between the observed phenotypic values and the predicted genetic
      values, and these two resultant variance components are used for calculating the
      unbiased heritability. We also demonstrated that the heritability calculated
      through cross validation is equivalent to trait predictability, which objectively
      reflects the applicability of the GS models. The proposed method can be
      implemented with the Mixed Procedure in SAS or with our R package "GSMX" which is
      publically available at https://cran.r-project.org/web/packages/GSMX/index.html .

PMID- 29057970
TI  - Deterioration of the Hanson Logboat: chemical and imaging assessment with removal
      of polyethylene glycol conserving agent.
AB  - The state of preservation of wood in two samples from the Hanson Logboat,
      currently on display in Derby Museum and Art Gallery, was analysed using
      elemental analysis (EA), pyrolysis-gas chromatography/flame ionisation detection
      (Py-GC/FID), pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) and
      scanning electron microscopy (SEM). The samples were collected in 2003, after the
      boat had undergone conservation, and in 2011 after the condition of the boat
      began to deteriorate. Solvent extraction enabled removal of polyethylene glycol,
      with which the wood had been impregnated during conservation, allowing the
      degradation of the cellulose and lignin polymeric components of the woods to be
      assessed. Elemental compositions (C, H, N, O, S), Py-GC/FID, Py-GC/MS and SEM
      imaging reveal extensive degradation of the wood polymers during the eight year
      period since conservation.

PMID- 29057971
TI  - PTEN-L promotes type I interferon responses and antiviral immunity.
AB  - Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a well-known
      tumor suppressor that acts as a dual-specificity phosphatase and is frequently
      mutated in human cancer. Our previous work has demonstrated that PTEN also plays
      a vital role in type I interferon responses and antiviral innate immunity.
      Recently, a translational variant of PTEN with a long N-terminal extension (PTEN
      L) has been discovered that is secreted into the extracellular environment and
      enters recipient cells, where it exerts a phosphatase function antagonistic to
      PI3K/Akt signaling and tumorigenesis. In this study, we demonstrate that PTEN-L
      promotes type I interferon responses and antiviral innate immunity during viral
      infection in a phosphatase activity-dependent manner. Compared with canonical
      PTEN, PTEN-L also exerts its antiviral function when it is applied exogenously in
      protein form. This finding was confirmed in cell cultures and mouse infection
      models. Furthermore, PTEN-L enhances the responses of both type I interferon and
      proinflammatory cytokines, thus suggesting that PTEN-L might possess additional
      functions compared with those of PTEN. Thus, the antiviral function of PTEN-L may
      open an avenue for the use of PTEN-L in antiviral therapy, particularly in
      patients with PTEN-deficient tumors.

PMID- 29057972
TI  - Relief of YAP-mediated inhibition by IKKE promotes innate antiviral immunity.

PMID- 29057973
TI  - Revisiting GM-CSF as an adjuvant for therapeutic vaccines.

PMID- 29057974
TI  - Engineering a short-chain dehydrogenase/reductase for the stereoselective
      production of (2S,3R,4S)-4-hydroxyisoleucine with three asymmetric centers.
AB  - Fenugreek is a dietary supplement for anti-aging and human health. (2S,3R,4S)-4
      hydroxyisoleucine (4-HIL), which is extracted from fenugreek seeds, is expected
      to be a promising orally active drug for diabetes and diabetic nephropathy
      because of its insulinotropic effect. Although several chemical synthesis methods
      of 4-HIL have been proposed, these methods require multistep reactions to control
      the stereochemistry of 4-HIL. In this study, we modified the key enzyme 4-HIL
      dehydrogenase (HILDH) to overcome the biggest limitation in commercial-scale
      production of 4-HIL. As a result, an effective one-step carbonyl reduction to
      produce (2S,3R,4S)-4-HIL was successfully accomplished with strict
      stereoselectivity (>99% de). Mass production of (2S,3R,4S)-4-HIL by our synthetic
      method could have a significant contribution to the prevention of diabetes,
      dyslipidemia, and Alzheimer's disease. (120 words/200 words).

PMID- 29057975
TI  - Antibiotics ameliorate lupus-like symptoms in mice.
AB  - Gut microbiota and the immune system interact to maintain tissue homeostasis, but
      whether this interaction is involved in the pathogenesis of systemic lupus
      erythematosus (SLE) is unclear. Here we report that oral antibiotics given during
      active disease removed harmful bacteria from the gut microbiota and attenuated
      SLE-like disease in lupus-prone mice. Using MRL/lpr mice, we showed that
      antibiotics given after disease onset ameliorated systemic autoimmunity and
      kidney histopathology. They decreased IL-17-producing cells and increased the
      level of circulating IL-10. In addition, antibiotics removed Lachnospiraceae and
      increased the relative abundance of Lactobacillus spp., two groups of bacteria
      previously shown to be associated with deteriorated or improved symptoms in
      MRL/lpr mice, respectively. Moreover, we showed that the attenuated disease
      phenotype could be recapitulated with a single antibiotic vancomycin, which
      reshaped the gut microbiota and changed microbial functional pathways in a time
      dependent manner. Furthermore, vancomycin treatment increased the barrier
      function of the intestinal epithelium, thus preventing the translocation of
      lipopolysaccharide, a cell wall component of Gram-negative Proteobacteria and
      known inducer of lupus in mice, into the circulation. These results suggest that
      mixed antibiotics or a single antibiotic vancomycin ameliorate SLE-like disease
      in MRL/lpr mice by changing the composition of gut microbiota.

PMID- 29057976
TI  - Analyzing homoeolog expression provides insights into the rediploidization event
      in gynogenetic hybrids of Carassius auratus red var. * Cyprinus carpio.
AB  - Rediploidization is considered to be a part of the evolutionary history of
      allotetraploids, and resulted in the emergence of novel epigenetic regulatory
      activities. To study the changing patterns of gene expression following the
      reduction of a genome by 50%, we used RNA-seq and quantitative real-time PCR
      (qPCR) to investigate total gene expression and homoeolog expression in three
      hybrids of a C. auratus red var. (2n = 100, ?) (R) and C. carpio (2n = 100, ?)
      (C) (i.e., F1, F18, and G4) and their original parents. A comparison of homoeolog
      expression between G4 and F18 identified 7 genes (0.22%) that exhibited novel R/C
      homoeolog expression patterns in G4, while 4 genes (0.12%) were affected by R/C
      homoeolog silencing. We determined the direction and extent of the homoeolog
      expression bias (HEB). The C-HEB genes (i.e., nrp1a and igf1) and R-HEB genes
      (i.e., fgf23 and esm1) provided insights into the effects of the dominance of one
      parental homoeolog expression on growth regulation. This dominance may contribute
      to the rapid growth of G4 fish. Our findings may be relevant for clarifying the
      relationship between growth heterosis and differences in homoeolog expression
      patterns.

PMID- 29057977
TI  - Myosin X is recruited to nascent focal adhesions at the leading edge and induces
      multi-cycle filopodial elongation.
AB  - Filopodia protrude from the leading edge of cells and play important roles in
      cell motility. Here we report the mechanism of myosin X (encoded by Myo10)
      induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin
      and integrin-beta first accumulated at the cell's leading edge. Myosin X was then
      gathered at these sites, gradually clustered by lateral movement, and
      subsequently initiated filopodia formation. During filopodia extension, we found
      the translocation of Arp2/3 and integrin-beta along filopodia. Arp2/3 and
      integrin-beta then became localized at the tip of filopodia, from where myosin X
      initiated the second extension of filopodia with a change in extension direction,
      thus producing long filopodia. Elimination of integrin-beta, Arp2/3 and vinculin
      by siRNA significantly attenuated the myosin-X-induced long filopodia formation.
      We propose the following mechanism. Myosin X accumulates at nascent focal
      adhesions at the cell's leading edge, where myosin X promotes actin convergence
      to create the base of filopodia. Then myosin X moves to the filopodia tip and
      attracts integrin-beta and Arp2/3 for further actin nucleation. The tip-located
      myosin X then initiates the second cycle of filopodia elongation to produce the
      long filopodia.

PMID- 29057978
TI  - The Staphylococcus aureus extracellular matrix protein (Emp) has a fibrous
      structure and binds to different extracellular matrices.
AB  - The extracellular matrix protein Emp of Staphylococcus aureus is a secreted
      adhesin that mediates interactions between the bacterial surface and
      extracellular host structures. However, its structure and role in staphylococcal
      pathogenesis remain unknown. Using multidisciplinary approaches, including
      circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy,
      transmission electron (TEM) and immunogold transmission electron microscopy,
      functional ELISA assays and in silico techniques, we characterized the Emp
      protein. We demonstrated that Emp and its truncated forms bind to suprastructures
      in human skin, cartilage or bone, among which binding activity seems to be higher
      for skin compounds. The binding domain is located in the C-terminal part of the
      protein. CD spectroscopy revealed high contents of beta-sheets (39.58%) and
      natively disordered structures (41.2%), and TEM suggested a fibrous structure
      consisting of Emp polymers. The N-terminus seems to be essential for
      polymerization. Due to the uncommonly high histidine content, we suggest that Emp
      represents a novel type of histidine-rich protein sharing structural similarities
      to leucine-rich repeats proteins as predicted by the I-TASSER algorithm. These
      new findings suggest a role of Emp in infections of deeper tissue and open new
      possibilities for the development of novel therapeutic strategies.

PMID- 29057979
TI  - Zymophore identification enables the discovery of novel phenylalanine ammonia
      lyase enzymes.
AB  - The suite of biological catalysts found in Nature has the potential to contribute
      immensely to scientific advancements, ranging from industrial biotechnology to
      innovations in bioenergy and medical intervention. The endeavour to obtain a
      catalyst of choice is, however, wrought with challenges. Herein we report the
      design of a structure-based annotation system for the identification of
      functionally similar enzymes from diverse sequence backgrounds. Focusing on an
      enzymatic activity with demonstrated synthetic and therapeutic relevance, five
      new phenylalanine ammonia lyase (PAL) enzymes were discovered and characterised
      with respect to their potential applications. The variation and novelty of
      various desirable traits seen in these previously uncharacterised enzymes
      demonstrates the importance of effective sequence annotation in unlocking the
      potential diversity that Nature provides in the search for tailored biological
      tools. This new method has commercial relevance as a strategy for assaying the
      'evolvability' of certain enzyme features, thus streamlining and informing
      protein engineering efforts.

PMID- 29057980
TI  - ROCK inhibition with Fasudil induces beta-catenin nuclear translocation and
      inhibits cell migration of MDA-MB 231 human breast cancer cells.
AB  - Tumor aggressiveness is usually associated with metastasis. MDA-MB 231, a triple
      negative breast cancer (TNBC), is an aggressive type of breast cancer and
      associated with early metastasis. The Rho/ROCK pathway is a key regulator of cell
      motility involving cytoskeleton regulation through stabilization of actin
      filaments and stress fiber formation. In this study we show that Fasudil, a ROCK
      inhibitor, inhibited the migration of MDA-MB 231 and A549 cells, without altering
      the viability of these cells at the concentration of 10 MUM, modified tumor cell
      morphology, with disorganization of stress fibers and promotes activation of the
      canonical-Wnt/beta-catenin pathway. Therefore, Fasudil present a promising
      approach to the prevention of breast cancer metastasis through a different
      mechanism of action from the well-known one.

PMID- 29057981
TI  - A New Generation of Arachidonic Acid Analogues as Potential Neurological Agent
      Targeting Cytosolic Phospholipase A2.
AB  - Cytosolic phospholipase A2 (cPLA2) is an enzyme that releases arachidonic acid
      (AA) for the synthesis of eicosanoids and lysophospholipids which play critical
      roles in the initiation and modulation of oxidative stress and neuroinflammation.
      In the central nervous system, cPLA2 activation is implicated in the pathogenesis
      of various neurodegenerative diseases that involves neuroinflammation, thus
      making it an important pharmacological target. In this paper, a new class of
      arachidonic acid (AA) analogues was synthesized and evaluated for their ability
      to inhibit cPLA2. Several compounds were found to inhibit cPLA2 more strongly
      than arachidonyl trifluoromethyl ketone (AACOCF3), an inhibitor that is commonly
      used in the study of cPLA2-related neurodegenerative diseases. Subsequent
      experiments concluded that one of the inhibitors was found to be cPLA2-selective,
      non-cytotoxic, cell and brain penetrant and capable of reducing reactive oxygen
      species (ROS) and nitric oxide (NO) production in stimulated microglial cells.
      Computational studies were employed to understand how the compound interacts with
      cPLA2.

PMID- 29057983
TI  - Electrodeposition of tin on Nafion-bonded carbon black as an active catalyst
      layer for efficient electroreduction of CO2 to formic acid.
AB  - Electroreduction of CO2 to formic acid (ERCF) based on gas diffusion electrodes
      (GDEs) has been considered as a promising method to convert CO2 into value-added
      chemicals. However, current GDEs for ERCF suffer from low efficiency of electron
      transfer. In this work, a novel Sn-based gas diffusion electrode (ESGDE) is
      prepared by electrodepositing Sn on Nafion-bonded carbon black as catalyst layer
      to enhance electron transfer and thus the efficiency of ERCF. The highest Faraday
      efficiency (73.01 +/- 3.42%), current density (34.21 +/- 1.14 mA cm-2) and
      production rate (1772.81 +/- 59.08 MUmol m-2 s-1) of formic acid are obtained by
      using the ESGDE with electrodeposition time of 90 s in 0.5 M KHCO3 solution,
      which are one of the highest values obtained from Sn-based gas diffusion
      electrodes under similar conditions. The notable efficiency of ERCF achieved here
      should be attributed to the enhancement in the reactants transfer as well as the
      three-dimensional reaction zone. This work will be helpful for the industrial
      application of GDEs in EFCF.

PMID- 29057982
TI  - Characterization of serum miRNAs as molecular biomarkers for acute Stanford type
      A aortic dissection diagnosis.
AB  - Early and convenient diagnosis is urgently needed for acute Stanford type A
      aortic dissection (AAAD) patients due to its high mortality within the first 48
      hours. Circulating microRNAs (miRNAs) are promising biomarkers of cardiovascular
      diseases, however, little is known about circulating miRNAs involved in AAAD.
      Here, the blood serum was sampled from 104 AAAD+ patients and 103 age-matched
      donors. Initial screening was conducted using the TaqMan Low Density Array
      followed by RT-qPCR confirmation. According to the two-phase selection and
      validation process, we found that miR-25, miR-29a and miR-155 were significantly
      elevated, while miR-26b was markedly decreased in AAAD+ serum samples compared
      with AAAD- individuals. Most importantly, for individuals with hypertension,
      which is a major contributor to AAAD, the 4-miRNA panel also showed high accuracy
      in predicting those who are more likely to develop AAAD. In the blind trial set,
      the panel correctly classified 93.33% AAAD+ patients and 86.67% controls from the
      hypertension cohort. Finally, the serum miRNA-based biomarker for early AAAD
      detection was supported by a retrospective analysis. Taken together, we identify
      a distinct profile of 4-miRNA that can serve as a noninvasive biomarker for AAAD
      diagnosis, especially for those with hypertension.

PMID- 29057984
TI  - Membrane binding of the insertion sequence of Proteus vulgaris L-amino acid
      deaminase stabilizes protein structure and increases catalytic activity.
AB  - Proteus vulgaris L-amino acid deaminase (pvLAAD) belongs to a class of bacterial
      membrane-bound LAADs mainly express in genus Proteus, Providencia and Morganella.
      These LAADs employ a non-cleavable N-terminal twin-arginine translocation (Tat)
      peptide to transport across membrane and bind to bacterial surface. Recent
      studies revealed that a hydrophobic insertion sequence (INS) in these LAADs also
      interacts with bacterial membrane. However, the functional significance of INS
      membrane interaction is not clear. In this study, we made site-directed
      mutagenesis on the surface-exposed hydrophobic residues of pvLAAD INS, and we
      found that these mutations impaired the INS-membrane interaction but did not
      affect pvLAAD activity in the solution. We further found that when cell membrane
      is present, the catalytic activity can be increased by 8~10 folds for wild-type
      but not INS-mutated pvLAAD, indicating that the INS-membrane interaction is
      necessary for increasing activity of pvLAAD. Molecular dynamic (MD) simulations
      suggested that INS is flexible in the solution, and its conformational dynamics
      could lead to substrate channel distortion. Circular dichroism (CD) spectroscopy
      experiments indicated that bacterial membrane was able to maintain the
      conformation of INS. Our study suggests the function of the membrane binding of
      INS is to stabilize pvLAAD structure and increase its catalytic activity.

PMID- 29057985
TI  - Molecular spectrum of excision repair cross-complementation group 8 gene defects
      in Chinese patients with Cockayne syndrome type A.
AB  - There are two genetics complementary groups Cockayne syndrome type A and B (CS-A
      and CS-B OMIM 216400, 133540), which is a rare autosomal recessive segmental
      progeroid syndrome. Homozygous or compound heterozygous mutations in the excision
      repair cross-complementation group 8 gene (ERCC8) result in CS-A, and mutations
      in ERCC6 result in CS-B. Homozygous ERCC6/ERCC8 mutations also result in UV
      sensitive syndrome. In this study, twenty-one Han Chinese patients with CS were
      investigated to identify mutations in ERCC8/ERCC6, of which thirteen cases with
      CS-A were identified with the mutations of ERCC8. There are five types mutations
      of ERCC8 in our study, such as exon 4 rearrangement, c.394_398delTTACA,
      c.299insA, c.843 + 2 T > C, and c.2 T > A. An estimated frequency of exon 4
      rearrangement accounts for 69.23% and c.394_398delTTACA accounts for 11.53% in
      our cohort. Haplotype analysis revealed that the exon 4 rearrangement and
      c.394_398delTTACA mutations originated from a common founder in the Chinese
      population respectively. With the identification of three novel ERCC8 mutations,
      this study expanded the molecular spectrum of known ERCC8 defects, and
      furthermore, suggests that the exon 4 rearrangement and c.394_398delTTACA
      mutations may be a common underlying cause of CS-A in the Chinese population,
      which is different from that in other populations.

PMID- 29057986
TI  - Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet
      and relationship to metabolic syndrome.
AB  - Reduced gut microbiome diversity is associated with multiple disorders including
      metabolic syndrome (MetS) features, though metabolomic markers have not been
      investigated. Our objective was to identify blood metabolite markers of gut
      microbiome diversity, and explore their relationship with dietary intake and
      MetS. We examined associations between Shannon diversity and 292 metabolites
      profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females
      from TwinsUK using linear regressions adjusting for confounders and multiple
      testing (Bonferroni: P < 1.71 * 10-4). We replicated the top results in an
      independent sample of 420 individuals as well as discordant identical twin pairs
      and explored associations with self-reported intakes of 20 food groups.
      Longitudinal changes in circulating levels of the top metabolite, were examined
      for their association with food intake at baseline and with MetS at endpoint.
      Five metabolites were associated with microbiome diversity and replicated in the
      independent sample. Higher intakes of fruit and whole grains were associated with
      higher levels of hippurate cross-sectionally and longitudinally. An increasing
      hippurate trend was associated with reduced odds of having MetS (OR:
      0.795[0.082]; P = 0.026). These data add further weight to the key role of the
      microbiome as a potential mediator of the impact of dietary intake on metabolic
      status and health.

PMID- 29057987
TI  - Magnetic resonance imaging features of dogs with incomplete recovery after acute,
      severe spinal cord injury.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVES: Describe the magnetic
      resonance imaging (MRI) features of dogs chronically impaired after severe spinal
      cord injury (SCI) and investigate associations between imaging variables and
      residual motor function. SETTING: United States of America. METHODS:
      Thoracolumbar MRI from dogs with incomplete recovery months to years after
      clinically complete (paralysis with loss of pain perception) thoracolumbar SCI
      were reviewed. Lesion features were described and quantified. Gait was quantified
      using an ordinal, open field scale (OFS). Associations between imaging features
      and gait scores, duration of injury (DOI), or SCI treatment were determined.
      RESULTS: Thirty-five dogs were included. Median OFS was 2 (0-6), median DOI was
      13 months (3-83), and intervertebral disk herniation was the most common
      diagnosis (n = 27). Myelomalacia was the most common qualitative feature followed
      by cystic change; syringomyelia and fibrosis were uncommon. Lesion length
      corrected to L2 length (LL:L2) was variable (median LL:L2 = 3.5 (1.34-11.54)).
      Twenty-nine dogs had 100% maximum cross-sectional spinal cord compromise (MSCC)
      at the lesion epicenter and the length of 100% compromised area varied widely
      (median length 100% MSCC:L2 = 1.29 (0.39-7.64)). Length 100% MSCC:L2 was
      associated with OFS (p = 0.012). OFS was not associated with any qualitative
      features. DOI or treatment type were not associated with imaging features or
      lesion quantification. CONCLUSIONS: Lesion characteristics on MRI in dogs with
      incomplete recovery after severe SCI were established. Length of 100% MSCC was
      associated with hind limb motor function. Findings demonstrate a spectrum of
      injury severity on MRI among severely affected dogs, which is related to
      functional status.

PMID- 29057988
TI  - The meaning of work after spinal cord injury: a scoping review.
AB  - STUDY DESIGN: Scoping review. OBJECTIVES: To explore the meaning of work after
      spinal cord injury (SCI) in existing literature. METHODS: Arksey and O'Malley's
      widely used methodological framework for scoping reviews was used to guide this
      review. Studies involving adults with SCI, conducted using qualitative methods,
      and published in peer reviewed literature were identified based on key terms and
      searches in three databases (CINAHL, MEDLINE, PsycINFO). Further search steps
      included checking citations in identified articles and citation tracking for
      other relevant articles and reviews. Reported qualitative data were then
      thematically analysed to generate themes. RESULTS: Twelve studies were included.
      Three themes were identified across these studies that describe the meanings of
      work after spinal cord injury: re-developing a sense of self, re-establishing
      place in the community and regaining economic self-sufficiency. CONCLUSIONS: The
      varied meanings of work after SCI identified in this review may be used in
      rehabilitation programs to explore ideas about work, the types of work they wish
      to pursue, and the ways in which work may be meaningful for people with SCI, so
      as to identify individually and contextually relevant work. Taking account of
      meaning in ICF based models of work participation could enhance patient-centred
      approaches in SCI rehabilitation.

PMID- 29057989
TI  - Physical therapy is targeted and adjusted over time for the rehabilitation of
      locomotor function in acute spinal cord injury interventions in physical and
      sports therapy.
AB  - STUDY DESIGN: Prospective observational multicenter study. OBJECTIVES:
      Investigation of content, duration and adjustment of physical therapy for the
      rehabilitation of ambulation in acute spinal cord injury (SCI). SETTING: European
      Multicenter Study of SCI (EMSCI). METHODS: Physical therapy interventions during
      acute in-patient rehabilitation of eighty incomplete SCI patients (AIS B, C, D
      all lesion levels) were recorded using the SCI - Intervention Classification
      System. Mobility was documented using the Spinal Cord Independence Measurement
      (SCIM III), demographics and clinical data were retrieved from the EMSCI
      database. RESULTS: Overall recovery of locomotor function was categorized into
      three outcome groups (G1-G3). Of 76 initial wheelchair-using patients, 53.9%
      remained wheelchair user (G1), 25% regained moderate (G2) and 21.1% good walking
      (G3) capability. Strength training was the most frequently applied intervention
      of body function/-structure across all outcome groups (about 30% of all
      interventions), while interventions focusing on muscle tone and respiration were
      predominantly applied in wheelchair-dependent patients. Activity-focused
      interventions of transfer, transition, sitting were trained most intensively in
      outcome group G1, while walking and swimming were increasingly trained in
      patients with moderate and good walking outcomes. Physical therapy interventions
      of assistive and active trainings as well as corresponding training environments
      changed with the recovery of locomotor function. CONCLUSIONS: Physical therapy of
      locomotor function is targeted to individual patients' conditions and becomes
      adjusted to the progress of ambulation. Although the involved clinical sites were
      not following explicitly standardized rehabilitation programs, common patterns
      can be discerned which may form the basis of prospective standardized programs.

PMID- 29057990
TI  - Spinal cord injury and Alzheimer's disease risk: a population-based,
      retrospective cohort study.
AB  - STUDY DESIGN: Propensity score-matched, retrospective cohort study. OBJECTIVES:
      To determine the risk of developing Alzheimer's disease (AD) in patients with
      spinal cord injury (SCI). SETTING: The present study used Taiwan's National
      Health Insurance Research Database. METHODS: A total of 9257 patients who had ?2
      ambulatory visits with a diagnosis of SCI in 2001 were included in the SCI group.
      The non-SCI group consisted of 37,028 propensity score-matched patients without a
      diagnosis of SCI. The cumulative incidence of AD was estimated for each of the
      two patient groups using the Kaplan-Meier method. Stratified Cox proportional
      hazard regression was then employed to assess the influence of SCI on the risk of
      AD. RESULTS: During the follow-up period, 25 subjects in the SCI group and 57 in
      the non-SCI group developed AD. The cumulative incidence of AD in the SCI group
      was higher than in the non-SCI group (P = 0.0168); and the hazard ratio of AD for
      the SCI group, as compared to the non-SCI group, was 1.71 (95% CI 1.06-2.76, P =
      0.0273). CONCLUSIONS: This study suggests that patients with SCI have an
      increased risk of developing AD.

PMID- 29057991
TI  - Risks factors of mechanical ventilation in acute traumatic cervical spinal cord
      injured patients.
AB  - STUDY DESIGN: Descriptive retrospective study. OBJECTIVES: To analyze risk
      factors associated with mechanical ventilation (MV) in cases of acute traumatic
      Cervical Spinal Cord Injury (tCSCI). SETTING: Unidad de Lesionados Medulares,
      Complejo Hospitalario Universitario A Coruna, in Galicia (Spain). METHODS: The
      study included patients with tCSCI who were hospitalized between January 2010 and
      December 2014. The following variables were analyzed: age, gender, etiology,
      neurological level, ASIA (American Spinal Injury Association) grade, associated
      injuries, injury severity score (ISS), ASIA motor score (AMS) at admission and
      mortality. RESULTS: A total of 146 patients met the study's inclusion criteria.
      The majority were men (74.7%) with mean age of 62.6 (s.d. +/- 18.8) years. Sixty
      patients (41.1%) required MV. Mean age of ventilated vs. non-ventilated patients
      was 57.3 vs. 65.7. Men were more likely to require MV than women, ASIA grades A
      and B were also more likely to need MV than grades C and D, as well as patients
      with associated injuries. The AMS of patients receiving MV was lower than that of
      those who did not require MV (20.1 vs. 54.3). Moreover, the ISS was higher in
      patients receiving MV (31.2 vs. 13.4). An AMS <= 37 and an ISS >= 13 increased
      the risk of requiring MV by a factor of 11.98 and 7.28, respectively.
      CONCLUSIONS: Isolated factors associated with a greater risk of MV in tCSCI were:
      age, gender, ASIA grade, ISS and AMS. However, the only factor with a significant
      discriminatory ability to determine the need for MV was the AMS at admission.

PMID- 29057993
TI  - MultiFLEXX - The new multi-analyzer at the cold triple-axis spectrometer FLEXX.
AB  - The first experimental characterization of a multiple energy analysis wide angle
      backend for a cold triple-axis spectrometer is reported. The multi-analyzer
      module MultiFLEXX employs 155 detection channels which simultaneously probe an
      extensive range in wavevector and energy transfer. Successful mapping of magnetic
      excitations in MnF2 and Ho demonstrate order of magnitude gains in data
      collection efficiency using this novel type backend. MultiFLEXX is competitive to
      standard triple-axis spectroscopy in terms of energy resolution and signal-to
      noise ratio. A minority of the detector channels is affected by spurious signals
      inherent to this multiplexing concept. The characteristic signature of these
      spurious signals easily allows for their discrimination. The instrument concept
      focuses on detection efficiency in the horizontal scattering plane which makes it
      an ideal technique for fast mapping and parametric studies including extreme
      sample environment.

PMID- 29057992
TI  - Nutritional blood parameters and nutritional risk screening in patients with
      spinal cord injury and deep pressure ulcer-a retrospective chart analysis.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVES: To describe (i) the
      nutritional blood parameters (NBP) and the nutritional risk screening (NRS) in
      patients with spinal cord injury (SCI) and pressure ulcers (PU) III and IV
      according to the EPUAP classification, and (ii) the relationship between both NBP
      and NRS. SETTING: SCI acute care and rehabilitation clinic in Switzerland.
      METHODS: The NBPs were measured upon the admission of patients treated for PU III
      and IV between 11/2011 and 12/2014. Descriptive analyses and group comparisons
      were done. RESULTS: A total of 170 patients, including 42 (25%) women, 19 (12%)
      people with paraplegia and 104 (61%) people with traumatic SCI, were admitted and
      analyzed. Pathologic blood values and NBP were found for c-reactive protein
      (83%), vitamin D (73%), protein (41%), erythrocyte sedimentation rate (ESR)
      (41%), albumin (34%), hemoglobin (34%), zinc (29%), folic acid (22%), transferrin
      (15.3%), and copper (1.2%). Overall, the NRS was >3 in 39% of the patients,
      wherefrom 28% in patients with PU III and 44% with PU IV (p=0.07). No statistical
      significant differences were found between patients with PU III and IV in terms
      of NBP and NRS. CONCLUSIONS: We found abnormal values in NBP and in NRS in a
      significant number of patients with SCI and PU of both III and IV. Both
      laboratory examinations and nutritional assessments at admission can help to
      detect and correct the nutritional deficits in patients at risk. Neither the
      grade of the PUs, nor the NBP or the NRS can replace one another.

PMID- 29057995
TI  - Author Correction: Surface properties of SAR11 bacteria facilitate grazing
      avoidance.
AB  - In the version of this Letter originally published, the authors incorrectly
      stated that primers 28F-519R were reported in ref. 54 to underestimate the
      abundance of SAR11 in the ocean. This statement has now been amended in all
      versions of the Letter.

PMID- 29057994
TI  - Effects of herpes simplex virus vectors encoding poreless TRPV1 or protein
      phosphatase 1alpha in a rat cystitis model induced by hydrogen peroxide.
AB  - Enhanced afferent excitability is considered to be an important
      pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS).
      In addition, transient receptor potential vanilloid-1 (TRPV1) receptors are known
      to be involved in afferent sensitization. Animals with hydrogen peroxide (HP)
      induced cystitis have been used as a model exhibiting pathologic characteristics
      of chronic inflammatory condition of the bladder. This study investigated the
      effect of gene therapy with replication-defective herpes simplex virus (HSV)
      vectors encoding poreless TRPV1 (PL) or protein phosphatase 1 alpha (PP1alpha), a
      negative regulator of TRPV1, using a HP-induced rat model of cystitis. HSV
      vectors encoding green fluorescent protein, PL or PP1alpha were inoculated into
      the bladder wall of female rats. After 1 week, 1% HP or normal saline was
      administered into the bladder, and the evaluations were performed 2 weeks after
      viral inoculation. In HP-induced cystitis rats, gene delivery of PL or PP1alpha
      decreased pain behavior as well as a reduction in the intercontraction interval.
      Also, both treatments reduced nerve growth factor expression in the bladder
      mucosa, reduced bladder inflammation characterized by infiltration of
      inflammatory cells and increased bladder weight. Taken together, HSV-mediated
      gene therapy targeting TRPV1 receptors could be effective for the treatment of
      IC/BPS.

PMID- 29057996
TI  - Phase transfer of TiO2 nanoparticles from water to ionic liquid triggered by
      phosphonic acid grafting.
AB  - Controlling the interface between TiO2 nanocrystals and ionic liquids is of high
      fundamental and applied interest for energy storage and conversion devices. Phase
      transfer of nanoparticles from a synthesis medium to a processing or an
      application medium plays a significant role in nanotechnology. Here we
      demonstrate that surface modification with phosphonic acids bearing cationic end
      groups can trigger the phase transfer of TiO2 nanoparticles from an aqueous sol
      to a typical water-immiscible ionic liquid, [Emim][NTf2]. The transfer involves
      both the grafting of the phosphonic acid moiety and the exchange of the counter
      ion of the cationic end-group by NTf2 anions, as demonstrated by solid-state NMR,
      elemental analysis and independent grafting and ion exchange experiments.
      Furthermore, the colloidal stability of the TiO2 sols in [Emim][NTf2] strongly
      depends on the hydrophobic character of the cationic end-groups.

PMID- 29057997
TI  - Defining the domains of Cia2 required for its essential function in vivo and in
      vitro.
AB  - The cytosolic iron-sulfur cluster assembly (CIA) system biosynthesizes iron
      sulfur (FeS) cluster cofactors for cytosolic and nuclear proteins. The yeast Cia2
      protein is the central component of the targeting complex which identifies apo
      protein targets in the final step of the pathway. Herein, we determine that Cia2
      contains five conserved motifs distributed between an intrinsically disordered N
      terminal domain and a C-terminal domain of unknown function 59 (DUF59). The
      disordered domain is dispensible for binding the other subunits of the targeting
      complex, Met18 and Cia1, and the apo-target Rad3 in vitro. While in vivo assays
      reveal that the C-terminal domain is sufficient to support viability, several
      phenotypic assays indicate that deletion of the N-terminal domain negatively
      impacts CIA function. We additionally establish that Glu208, located within a
      conserved motif found only in eukaryotic DUF59 proteins, is important for the
      Cia1-Cia2 interaction in vitro. In vivo, E208A-Cia2 results in a diminished
      activity of the cytosolic iron sulfur cluster protein, Leu1 but only modest
      effects on hydroxyurea or methylmethane sulfonate sensitivity. Finally, we
      demonstrate that neither of the two highly conserved motifs of the DUF59 domain
      are vital for any of Cia2's interactions in vitro yet mutation of the DPE motif
      in the DUF59 domain results in a nonfunctional allele in vivo. Our observation
      that four of the five highly conserved motifs of Cia2 are dispensable for
      targeting complex formation and apo-target binding suggests that Cia2 is not
      simply a protein-protein interaction mediator but it likely possesses an
      additional, currently cryptic, function during the final cluster insertion step
      of CIA.

PMID- 29057998
TI  - A super stretchable and sensitive strain sensor based on a carbon nanocoil
      network fabricated by a simple peeling-off approach.
AB  - Despite the tremendous progress in wearable and smart strain sensors, it is still
      a challenge to develop a highly sensitive, stretchable, and low-cost sensor.
      Herein, a super stretchable and sensitive strain sensor fabricated by a simple
      peeling-off approach is reported. The strain sensor is prepared by peeling off a
      thin as-grown carbon nanocoil (CNC) film from a substrate using a stretchable
      polydimethylsiloxane (PDMS) film or a flexible adhesive tape. Herein, we took
      advantage of the spring-like morphology and the original network of the CNCs. The
      sensor is used to detect pressure, tension, and bend. The strain range and
      maximum real-time gauge factor reach 260% and 190, respectively, with a rapid
      response time (less than 12 ms). The contrary resistance responses under tension
      and bend make it possible to distinguish the direction and type of strain. The
      sensor is used to monitor a strain over a wide range, from human pulse to the
      impact of a 0.9 kg weight. The high sensitivity and stretchability, easy and
      cheap fabrication, and effective interaction with human motions suggest the great
      potential applications of this sensor in wearable strain sensors and smart
      systems.

PMID- 29057999
TI  - Frontiers in radionuclide imaging and therapy, a chemical journey from naturally
      radioactive elements to targeted theranostic agents.

PMID- 29058000
TI  - DFT study of CO2 conversion on InZr3(110) surface.
AB  - Methanol and methane synthesis from CO2 hydrogenation on a InZr3(110) surface has
      been studied using density functional theory calculations. The CO2 can be
      chemically adsorbed via a polydentated configuration and the H2 molecule can
      dissociate to H atoms spontaneously. The methanol is primarily formed via the
      HCOO route instead of the RWGS route, due to its higher activation barrier of
      1.35 eV for HCO hydrogenation. In the HCOO route, the adsorbed CO2 consecutively
      hydrogenates to form HCOO, H2COO and the H3CO species. The H3COH is produced via
      the reaction of H3CO with a surface OH group. Furthermore, the C-O bonds of CO,
      CHO, CH2O and CH3O species prefer to dissociate to C, CH, CH2 CH3 and surface O
      species. Methane is formed via the hydrogenation of CHx (x = 0-3) monomers with
      the highest activation barrier of 1.19 eV for CH3 hydrogenation, which is higher
      than that of the hydrogenation of H2COO in methanol synthesis via the HCOO route.
      The surface O species formed during CO2 hydrogenation reacts with the adsorbed H2
      molecule to produce an OH group which reacts with a surface H atom to form H2O
      with an activation barrier of 1.13 eV, which then desorbs to the gas phase. Our
      calculated results indicate that the InZr3 alloy is a potential candidate
      catalyst for CO2 utilization and conversion.

PMID- 29058001
TI  - Alloying-assisted phonon engineering of layered BiInSe3@nickel foam for efficient
      solar-enabled water evaporation.
AB  - The fresh water crisis has emerged as one of the most urgent bottlenecks
      hindering the rapid development of modern industry and society. Solar energy
      driven water evaporation represents a potential green and sustainable solution to
      address this issue. Herein, for the first time, centimeter-scale BiInSe3-coated
      nickel foam (BiInSe3@NF) as an efficient solar-enabled evaporator was
      successfully achieved and exploited for solar energy-driven water evaporation.
      Benefitting from multiple scattering-induced light trapping of the rough
      substrate, strong light-matter interaction and intermediate band (IB)-induced
      efficient phonon emission of BiInSe3, the BiInSe3@NF device achieved a high
      evaporation rate of 0.83 kg m-2 h-1 under 1 sun irradiation, which is 2.5 times
      that of pure water. These figures-of-merit are superior to recently reported
      state-of-the-art photothermal conversion materials, such as black titania,
      plasmonic assembly and carbon black. In addition, superior stability over a
      period of 60 days was demonstrated. In summary, the current contribution depicts
      a facile scenario for design, production and application of an economical and
      efficient solar-enabled BiInSe3@NF evaporator. More importantly, the phonon
      engineering strategy based on alloying induced IB states can be readily applied
      to other analogous van der Waals materials and a series of superior vdWM alloys
      toward photothermal applications can be expected in the near future.

PMID- 29058002
TI  - A microfluidic microinjector for toxicological and developmental studies in
      Drosophila embryos.
AB  - Microinjection is an established and reliable method to deliver biological
      reagents such as transgenic constructs and drugs, to specific locations inside
      organisms such as the Drosophila embryo and C. elegans worm. In this paper, a
      simple compliant mechanism based PDMS-microinjection system has been
      demonstrated. Unlike conventional microinjectors, this unique system could allow
      one to precisely insert a long taper microneedle laterally and at various
      positions inside the length of the Drosophila embryo (up to 250 MUm) with the
      resolution of 5 MUm. Volumes as low as 30 pL with accuracy of +/-10 pL were
      delivered inside the embryo via pressure pulses. The device has been used to
      study the effect of toxins on cardiogenesis in Drosophila embryos. Using this
      device, we demonstrate that the cardioblast (CB) migration velocity is modified
      in a dose sensitive manner to varying doses of injected sodium azide (NaN3) and,
      for the first time, quantify the effect of the toxin on heart assembly. Injection
      with 40 pL of NaN3 was shown to decrease CB migration velocity and filopodia
      number at concentrations above 10 mM, while embryos injected with the tracer
      Rhodamine B (0 mM NaN3) displayed no significant difference when compared to
      uninjected embryos. This device can be potentially used for other embryonic
      assays, which require accurate delivery of the reagents to a specific location
      within the embryo.

PMID- 29058003
TI  - Modelling of Dictyostelium discoideum movement in a linear gradient of
      chemoattractant.
AB  - Chemotaxis is a ubiquitous biological phenomenon in which cells detect a spatial
      gradient of chemoattractant, and then move towards the source. Here we present a
      position-dependent advection-diffusion model that quantitatively describes the
      statistical features of the chemotactic motion of the social amoeba Dictyostelium
      discoideum in a linear gradient of cAMP (cyclic adenosine monophosphate). We fit
      the model to experimental trajectories that are recorded in a microfluidic setup
      with stationary cAMP gradients and extract the diffusion and drift coefficients
      in the gradient direction. Our analysis shows that for the majority of gradients,
      both coefficients decrease over time and become negative as the cells crawl up
      the gradient. The extracted model parameters also show that besides the expected
      drift in the direction of the chemoattractant gradient, we observe a nonlinear
      dependency of the corresponding variance on time, which can be explained by the
      model. Furthermore, the results of the model show that the non-linear term in the
      mean squared displacement of the cell trajectories can dominate the linear term
      on large time scales.

PMID- 29058004
TI  - First-principles study of Ga-vacancy induced magnetism in beta-Ga2O3.
AB  - First principles calculations based on density functional theory were performed
      to study the electronic structure and magnetic properties of beta-Ga2O3 in the
      presence of cation vacancies. We investigated two kinds of Ga vacancies at
      different symmetry sites and the consequent structural distortion and defect
      states. We found that both the six-fold coordinated octahedral site and the four
      fold coordinated tetrahedral site vacancies can lead to a spin polarized ground
      state. Furthermore, the calculation identified a relationship between the spin
      polarization and the charge states of the vacancies, which might be explained by
      a molecular orbital model consisting of uncompensated O2- 2p dangling bonds. The
      calculations for the two vacancy systems also indicated a potential long-range
      ferromagnetic order which is beneficial for spintronics application.

PMID- 29058005
TI  - Application of spin-ratio scaled MP2 for the prediction of intermolecular
      interactions in chemical systems.
AB  - Accurate prediction of intermolecular interactions plays a pivotal role in many
      areas of chemistry and biology including (but not limited to) the design of
      pharmaceuticals, solid electrolytes and food additives. Here we present the
      application of the recently developed spin-ratio scaled MP2 method (termed SRS
      MP2) to six different datasets covering a wide range of interaction types from
      strong hydrogen bonding to van der Waals dispersion and pi-pi stacking. The
      method achieves a remarkably low mean absolute error of 1.6 kJ mol-1 across all
      interaction types including semi-Coulombic systems such as organic ionic salts.
      The new SRS-MP2 method offers high level of accuracy for studying intermolecular
      interactions commonly found in molecular systems of chemical and biological
      relevance without the need for including additional terms in the formulation.
      This finding represents a new paradigm in the development of wavefunction-based
      methods for intermolecular interactions.

PMID- 29058006
TI  - Sequential microhydration of cationic 5-hydroxyindole (5HI+): infrared
      photodissociation spectra of 5HI+-Wn clusters (W = H2O, n <= 4).
AB  - Most biochemical processes occur in aqueous solution. Here, we characterize the
      initial microhydration steps of the 5-hydroxyindole cation (5HI+) in its 2A''
      ground electronic state by infrared photodissociation (IRPD) spectroscopy of 5HI+
      Wn-Lm clusters (W = H2O, L = Ar and N2, n <= 4, m <= 2) in a molecular beam and
      dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc
      pVTZ). Characteristic size- and isomer-dependent XH stretch frequencies (X = O,
      N) of 5HI+-Wn reveal information about the preferred cluster growth and solvation
      energies. The IRPD spectrum of 5HI+-W is a superposition of the spectra of two
      isomers, in which W is H-bonded to the acidic NH or OH group, whereby OHW
      hydrogen-bonds (H-bonds) are stronger than NHW H-bonds. Spectra of larger 5HI+-Wn
      clusters (n >= 2) elucidate the competition between interior ion solvation and
      the formation of H-bonded water networks. The nature and strengths of the
      competing H-bonds are quantified by the noncovalent interaction approach.
      Comparison to results for neutral 5HI-W and 5HI+-Ln clusters with nonpolar
      ligands reveals the effects of ionization and ligand type on the intermolecular
      interaction potential and cluster growth. Comparison to corresponding
      microhydrated clusters of the phenol, indole, and pyrrole cations illustrates the
      effects of substitution of functional groups and addition of aromatic rings on
      the hydration process.

PMID- 29058008
TI  - A study of the competitive multiple hydrogen bonding effect and its associated
      excited-state proton transfer tautomerism.
AB  - 1,8-Dihydroxynaphthalene-2,7-dicarbaldehyde (DHDA) has been strategically
      designed and synthesized with the aim to study the competitive multiple hydrogen
      bonding (H-bonding) effect and the associated excited-state intramolecular proton
      transfer reaction (ESIPT). In nonpolar solvents such as cyclohexane, equilibrium
      exists between the two H-bonding isomers DHDA-23_OO and DHDA-23_OI, both of which
      possess double intramolecular H-bonds. In polar, aprotic solvents such as CH2Cl2,
      DHDA-23_OO becomes the predominant species. Due to various degrees of H-bond
      induced changes of electronic configuration each isomer reveals a distinct
      absorption feature and excited-state behavior, in which DHDA-23_OI in cyclohexane
      undergoes double ESIPT in a stepwise manner, giving the first and second proton
      transfer tautomer emissions maximized at ~500 nm and 660 nm, respectively. As for
      DHDA-23_OO both single and double ESIPT are prohibited, resulting in an intense
      normal 450 nm emission band. In a single crystal DHDA-23_OI is the dominant
      species, which undergoes excited state double proton transfer, giving intense
      emission bands at 530 nm and 650 nm. The mechanism associated with competitive
      multiple H-bonding energetics and ESIPT was underpinned by detailed
      spectroscopy/dynamics and computational approaches.

PMID- 29058007
TI  - A cryptophane-based "turn-on" 129Xe NMR biosensor for monitoring calmodulin.
AB  - We present the first cryptophane-based "turn-on" 129Xe NMR biosensor, employing a
      peptide-functionalized cryptophane to monitor the activation of calmodulin (CaM)
      protein in solution. In the absence of CaM binding, interaction between the
      peptide and cryptophane completely suppresses the hyperpolarized 129Xe
      cryptophane NMR signal. Biosensor binding to Ca2+-activated CaM produces the
      expected 129Xe-cryptophane NMR signal.

PMID- 29058009
TI  - Enantioselective syntheses of atropisomers featuring a five-membered ring.
AB  - Atropisomerism is a fundamental property of molecules featuring a hindered
      rotation around a chemical bond. If six-membered ring biaryl or heterobiaryl
      atropisomers are the most popular ones, the focus of this feature article will be
      put on less common and more challenging five-membered ring containing
      atropisomers displaying either a stereogenic C-N or C-C bond. After an historical
      background, a description of the latest flourishing enantioselective strategies
      for the construction of this attractive family of atropisomers will be presented.

PMID- 29058010
TI  - A ratiometric electrochemical strategy for sensitive determination of Furin
      activity based on dual signal amplification and antifouling nanosurfaces.
AB  - Developing a sensitive and accurate method for Furin activity is still the
      bottleneck for understanding the role played by Furin in cell-surface systems and
      even in Alzheimer's disease. In this work, a ratiometric electrochemical
      biosensor was developed for sensitive and accurate determination of Furin
      activity in the cell based on dual signal amplification stemming from a peptide
      with multiple response sites and the antifouling gold nano-bellflowers (GBFs). A
      new peptide, HS-CMRVRR?YKDFDFG (P3), was designed for the first time to be
      selectively cleaved by Furin at site?. More importantly, this peptide P3
      constitutes three amino acid residues with the -COOH group subsequently used to
      bind with the response molecule of ferrocene, and can remarkably improve the
      determination sensitivity by about 2.3 fold. Meanwhile, GBFs stabilized by PEG
      were taken as a second element to magnify the signal of the ferrocene group via a
      large ratio surface area and good conductivity, as well as an antibiofouling
      nanosurface to reduce the biofouling of the electrode surface in cells. This
      double amplification strategy can greatly enhance the sensitivity of Furin
      detection by 6.5-fold, which is favorable for detection of low amounts of Furin.
      In addition, 5'-MB-GGCGCGA(T)13-SH-3' was co-assembled as an inner reference to
      provide a built-in element to correct the determination error resulting from a
      complicated analysis environment. Finally, this sensitive and accurate Furin
      biosensor was successfully applied to detect Furin activity in Furin
      overexpressed U251 and MDA-MB-468 cells. As far as we know, this is the first
      report to mention an electrochemical strategy to detect Furin activity in cells.

PMID- 29058011
TI  - Effect of fluorine substitution and position on phenylene spacer in carbazole
      based organic sensitizers for dye sensitized solar cells.
AB  - The preparation of a series of organic dyes having a carbazole donor,
      cyanoacrylic acid as an acceptor, and phenylene ring as a spacer with the
      difference in the positions of fluorine substitution is reported. Due to its
      unique properties of small size and high electronegativity, fluorine is now being
      extensively used to control the optoelectronic properties of organic conjugated
      materials. In this study, the results revealed that the specific position and
      number of fluorine substitution were very crucial to control the optical as well
      as the electrochemical properties of organic dyes. It was found that fluorine
      substitution led to a redshift in the absorption spectra of the dyes and reduced
      the band gap. The injection rate of photoexcited electrons was measured using
      time-resolved photoluminescence and the o-fluoro substituted dye MA1F-o showed
      the best electron injection dynamics. As a result of broad absorption and high
      electron injection rate, the dye MA1F-o outperformed other dyes with a power
      conversion efficiency of 4.02% (Jsc = 8.3 mA cm-2, Voc = 0.75 V and FF = 0.64).
      The non-fluorinated dye MA0F exhibited a power conversion efficiency of 3.23%
      (Jsc = 6.8, Voc = 0.72 and FF = 0.67). The dye MA1F-m exhibited the least molar
      absorption coefficient and a lower power conversion efficiency because of the
      meta inductive effect.

PMID- 29058012
TI  - Taming photo-induced oxidation degradation of dihydropyridine drugs through
      cocrystallization.
AB  - Cocrystallization of nifedipine (NFD) and isonicotinamide (INA) resulted in two
      monotropic cocrystal polymorphs. The thermodynamically more stable polymorph
      presents superior photostability compared to the other. Cocrystallization can be
      an efficient approach to address the stability deficit of dihydropyridine drugs.

PMID- 29058013
TI  - Drifting Away of a FET Endpoint: The Heart Rate in Danio rerio Embryos is
      Extremely Sensitive to Variation in Ambient Temperature.
AB  - Beyond the mere detection of presence or absence of heart beat in zebrafish
      (Danio rerio) embryos in a fish embryo test conducted referring to the OECD TG
      236 at 48 hpf (hours post fertilization) onwards, embryo heart rate may serve as
      an additional and very sensitive endpoint in ecotoxicological studies. But by
      including heart rate as a sublethal endpoint, care has to be taken of separating
      effects exerted by a tested compound from those exerted by temperature.
      Therefore, profound knowledge on the natural variation of zebrafish heart rates
      at defined temperatures as a basis for the assessment of gained results is
      mandatorily needed. As such continuous information in D. rerio is lacking from
      the literature, we designed a study covering a span of 12 degrees C (from 18 to
      30 degrees C in steps of 2 degrees C) to quantify the relationship between heart
      rate and temperature in D. rerio embryos 48 hpf. Conducting a multiple regression
      analysis, we found a considerably strong relationship between treatment
      temperature and the log10 of the heart rate, ranging from 82.8 beats per minute
      at 18 degrees C to 218.0 beats per minute at 30 degrees C. Our results therefore
      may serve as a reference for heart rates measured under normal conditions to be
      able to detect potential effects of contaminants in other studies when working
      under certain temperatures.

PMID- 29058014
TI  - Quantitative Rapid Assessment of Leukoaraiosis in CT : Comparison to Gold
      Standard MRI.
AB  - PURPOSE: The severity of white matter lesions (WML) is a risk factor of
      hemorrhage and predictor of clinical outcome after ischemic stroke; however, in
      contrast to magnetic resonance imaging (MRI) reliable quantification for this
      surrogate marker is limited for computed tomography (CT), the leading stroke
      imaging technique. We aimed to present and evaluate a CT-based automated rater
      independent method for quantification of microangiopathic white matter changes.
      METHODS: Patients with suspected minor stroke (National Institutes of Health
      Stroke scale, NIHSS < 4) were screened for the analysis of non-contrast
      computerized tomography (NCCT) at admission and compared to follow-up MRI. The
      MRI-based WML volume and visual Fazekas scores were assessed as the gold standard
      reference. We employed a recently published probabilistic brain segmentation
      algorithm for CT images to determine the tissue-specific density of WM space. All
      voxel-wise densities were quantified in WM space and weighted according to
      partial probabilistic WM content. The resulting mean weighted density of WM space
      in NCCT, the surrogate of WML, was correlated with reference to MRI-based WML
      parameters. RESULTS: The process of CT-based tissue-specific segmentation was
      reliable in 79 cases with varying severity of microangiopathy. Voxel-wise
      weighted density within WM spaces showed a noticeable correlation (r = -0.65)
      with MRI-based WML volume. Particularly in patients with moderate or severe
      lesion load according to the visual Fazekas score the algorithm provided reliable
      prediction of MRI-based WML volume. CONCLUSION: Automated observer-independent
      quantification of voxel-wise WM density in CT significantly correlates with
      microangiopathic WM disease in gold standard MRI. This rapid surrogate of white
      matter lesion load in CT may support objective WML assessment and therapeutic
      decision-making during acute stroke triage.

PMID- 29058015
TI  - WNT signaling, the development of the sympathoadrenal-paraganglionic system and
      neuroblastoma.
AB  - Neuroblastoma (NB) is a tumor of the sympathoadrenal system arising in children
      under 15 years of age. In Germany, NB accounts for 7% of childhood cancer cases,
      but 11% of cancer deaths. It originates from highly migratory progenitor cells
      that leave the dorsal neural tube and contribute neurons and glial cells to
      sympathetic ganglia, and chromaffin and supportive cells to the adrenal medulla
      and paraganglia. Clinically, histologically and molecularly, NBs present as
      extremely heterogeneous, ranging from very good to very poor prognosis. The
      etiology of NB still remains unclear and needs to be elucidated, however,
      aberrant auto- and paracrine embryonic cell communications seem to be likely
      candidates to initiate or facilitate the emergence, progression and regression of
      NB. The wingless-type MMTV integration site (WNT) family of proteins represents
      an evolutionary highly conserved signaling system that orchestrates
      embryogenesis. At least 19 ligands in the human, numerous receptors and co
      receptors are known, which control not only proliferation, but also cell
      polarity, migration and differentiation. Here we seek to interconnect aspects of
      WNT signaling with sympathoadrenal and paraganglionic development to define new
      WNT signaling cues in the etiology and progression of NB.

PMID- 29058016
TI  - Resculpting the binding pocket of APC superfamily LeuT-fold amino acid
      transporters.
AB  - Amino acid transporters are essential components of prokaryote and eukaryote
      cells, possess distinct physiological functions, and differ markedly in substrate
      specificity. Amino acid transporters can be both drug targets and drug
      transporters (bioavailability, targeting) with many monogenic disorders resulting
      from dysfunctional membrane transport. The largest collection of amino acid
      transporters (including the mammalian SLC6, SLC7, SLC32, SLC36, and SLC38
      families), across all kingdoms of life, is within the Amino acid-Polyamine
      organoCation (APC) superfamily. The LeuT-fold is a paradigm structure for APC
      superfamily amino acid transporters and carriers of sugars, neurotransmitters,
      electrolytes, osmolytes, vitamins, micronutrients, signalling molecules, and
      organic and fatty acids. Each transporter is specific for a unique sub-set of
      solutes, specificity being determined by how well a substrate fits into each
      binding pocket. However, the molecular basis of substrate selectivity remains, by
      and large, elusive. Using an integrated computational and experimental approach,
      we demonstrate that a single position within the LeuT-fold can play a crucial
      role in determining substrate specificity in mammalian and arthropod amino acid
      transporters within the APC superfamily. Systematic mutation of the amino acid
      residue occupying the equivalent position to LeuT V104 titrates binding pocket
      space resulting in dramatic changes in substrate selectivity in exemplar APC
      amino acid transporters including PAT2 (SLC36A2) and SNAT5 (SLC38A5). Our work
      demonstrates how a single residue/site within an archetypal structural motif can
      alter substrate affinity and selectivity within this important superfamily of
      diverse membrane transporters.

PMID- 29058017
TI  - Are work demands associated with mental distress? Evidence from women in rural
      India.
AB  - PURPOSE: High work demands might be a determinant of poor mental health among
      women in low- and middle-income countries, especially in rural settings where
      women experience greater amounts of labor-intensive unpaid work. Research
      originating from such settings is lacking. METHODS: We estimated the cross
      sectional association between work demands and mental distress among 3177 women
      living in 160 predominantly tribal communities in southern Rajasthan, India. A
      structured questionnaire captured the number of minutes women spent on various
      activities in the last 24 h, and we used this information to measure women's work
      demands, including the total work amount, nature of work (e.g., housework), and
      type of work (e.g., cooking). Mental distress was measured with the Hindi version
      of the 12-item General Health Questionnaire. We used negative binomial regression
      models to estimate the association between work demands (amount, nature, and
      type) and mental distress. RESULTS: On average, women spent more than 9.5 h a day
      on work activities. The most time, intensive work activity was caring for
      children, the elderly, or disabled (149 min). In adjusted models, we found a U
      shaped association between work amount and mental distress. High amounts of
      housework were associated with higher distress, whereas paid work and farmwork
      amount were not. Certain types of housework, including collecting water and
      cleaning, were associated with increased distress scores. CONCLUSIONS: We found
      an association between aspects of work demands and mental distress. Research in
      other contexts where women perform high amounts of unpaid work, particularly
      within the home or farm, is warranted.

PMID- 29058018
TI  - [Big Data Revolution or Data Hubris? : On the Data Positivism of Molecular
      Biology].
AB  - Genome data, the core of the 2008 proclaimed big data revolution in biology, are
      automatically generated and analyzed. The transition from the manual laboratory
      practice of electrophoresis sequencing to automated DNA-sequencing machines and
      software-based analysis programs was completed between 1982 and 1992. This
      transition facilitated the first data deluge, which was considerably increased by
      the second and third generation of DNA-sequencers during the 2000s. However, the
      strategies for evaluating sequence data were also transformed along with this
      transition. The paper explores both the computational strategies of automation,
      as well as the data evaluation culture connected with it, in order to provide a
      complete picture of the complexity of today's data generation and its intrinsic
      data positivism. This paper is thereby guided by the question, whether this data
      positivism is the basis of the big data revolution of molecular biology announced
      today, or it marks the beginning of its data hubris.

PMID- 29058019
TI  - Effects of arsenolipids on in vitro blood-brain barrier model.
AB  - Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids (AsLs)
      occurring in fish and edible algae, possess a substantial neurotoxic potential in
      fully differentiated human brain cells. Previous in vivo studies indicating that
      AsHCs cross the blood-brain barrier of the fruit fly Drosophila melanogaster
      raised the question whether AsLs could also cross the vertebrate blood-brain
      barrier (BBB). In the present study, we investigated the impact of several
      representatives of AsLs (AsHC 332, AsHC 360, AsHC 444, and two arsenic-containing
      fatty acids, AsFA 362 and AsFA 388) as well as of their metabolites (thio/oxo
      dimethylpropionic acid, dimethylarsinic acid) on porcine brain capillary
      endothelial cells (PBCECs, in vitro model for the blood-brain barrier). AsHCs
      exerted the strongest cytotoxic effects of all investigated arsenicals as they
      were up to fivefold more potent than the toxic reference species arsenite
      (iAsIII). In our in vitro BBB-model, we observed a slight transfer of AsHC 332
      across the BBB after 6 h at concentrations that do not affect the barrier
      integrity. Furthermore, incubation with AsHCs for 72 h led to a disruption of the
      barrier at sub-cytotoxic concentrations. The subsequent immunocytochemical
      staining of three tight junction proteins revealed a significant impact on the
      cell membrane. Because AsHCs enhance the permeability of the in vitro blood-brain
      barrier, a similar behavior in an in vivo system cannot be excluded.
      Consequently, AsHCs might facilitate the transfer of accompanying foodborne
      toxicants into the brain.

PMID- 29058020
TI  - [Changes in the patient population with proximal femur fractures over the last
      decade : Incidence, age, comorbidities, and length of stay].
AB  - BACKGROUND: Over the last decade, the percentage of people >65 years has
      increased from 16.6% to 20.7%. In industrialized countries, the annual incidence
      in people >65 years with a proximal femur fracture is about 600-900 per 100,000
      population. The incidence will increase by 3-5% per year. Guidelines advocate
      early surgery as soon as possible but within 24 h. External quality control
      requires surgical treatment within 48 h. In this study, the changes in the
      patient population with proximal femur fractures and their treatment during the
      last decade were investigated. METHODS: From 2005-2014, data of all patients >=65
      years with proximal femur fractures were recorded. The patients were treated in a
      level 1 trauma center certified by the German Society for Trauma Surgery. The
      evaluation was carried out by means of descriptive statistics. RESULTS: In all,
      2093 patients with proximal femur fractures (1164 trochanteric neck fractures and
      929 femoral neck fractures) were evaluated. The annual increase in the percentage
      of patients was 1.5-2%. Over the decade, the percentage of patients increased by
      20% and the average age increased by 2 years. There were no changes in
      comorbidities or case mix index during the investigation period. Despite the
      increase of the preoperative waiting times, a decrease in the total length of
      stay was found. DISCUSSION: The increase in the number of patients, as well as
      the requirements of the guidelines and external quality control are relevant
      challenges for the hospitals. More human and material resources (e. g., surgical
      capacity) are needed. The increase in the age of the patients, their
      comorbidities, and medication must be taken into account, e. g., in the context
      of geriatric orthopedic trauma centers.

PMID- 29058021
TI  - Contact area between femoral tunnel and interference screw in anatomic
      rectangular tunnel ACL reconstruction: a comparison of outside-in and trans
      portal inside-out techniques.
AB  - PURPOSE: The purpose of this study was to compare the femoral tunnel length, the
      femoral graft bending angle at the femoral tunnel aperture, and the contact area
      between the femoral tunnel wall and an interference screw used for fixation in
      anatomic rectangular tunnel anterior cruciate ligament (ACL) reconstruction (ART
      ACLR). METHODS: The study included 149 patients with primary ACL injury who
      underwent ART ACLR. Preoperatively, flexion angle of the index knee was checked
      under general anaesthesia. Those of less than 130 degrees  of passive flexion
      were assigned to the outside-in (OI) technique (78 patients), while the others to
      the trans-portal inside-out (TP) technique (71 patients). The patients underwent
      computed tomography with multiplanar reconstruction at 3-5 weeks post
      operatively. Femoral tunnel length, graft bending angle, and contact ratio
      between the IFS and femoral tunnel were assessed. P < 0.05 was considered
      statistically significant. RESULTS: The femoral tunnel length in the OI technique
      was significantly longer than that in the TP technique (P < 0.001). The femoral
      graft bending angle in the OI technique was significantly more acute than that in
      the TP technique (P < 0.001). The contact ratio in the OI technique was
      significantly larger than that in the TP technique at every point in the femoral
      tunnel (P < 0.001). CONCLUSIONS: The OI technique resulted in a more acute
      femoral graft bending angle, longer mean femoral tunnel length, and larger
      contact ratio than the TP technique after ART ACLR. LEVEL OF EVIDENCE:
      Retrospective comparative study, Level III.

PMID- 29058022
TI  - Neuromuscular exercises prevent severe knee injury in adolescent team handball
      players.
AB  - PURPOSE: Team handball is associated with a high risk of severe knee injury that
      needs to be reduced, particularly at the youth level. The purpose of this study
      was to show how an injury-prevention programme effectively reduces severe knee
      injury in adolescent team handball players. METHODS: Of 23 adolescent handball
      teams of both sexes, 13 were randomly allocated into the intervention group (168
      players) and 10 into the control group (111 players). Players of the intervention
      group regularly participated in an injury-prevention programme for one season.
      Handball exposure and sustained injuries were documented for both groups on a
      monthly basis. The primary outcome parameter of the injury-prevention programme
      was the incidence of severe knee injury. RESULTS: Of the 279 included players, 68
      (24%) sustained 82 injuries yielding an overall incidence of 1.85 injuries per
      1000 h handball exposure (intervention group: 50 injuries/incidence: 1.90/1000 h;
      control group: 32 injuries/incidence: 1.78/1000 h). Knee injury was the second
      most frequent injury in adolescent team handball. The primary outcome parameter,
      severe knee injury occurred significantly more often in the control group [mean
      age (SD) 15.1 (1.0), injury incidence 0.33/1000 h] than in the intervention group
      [mean age (SD) 14.9 (0.9), injury incidence 0.04/1000 h]. The odds ratio was 0.11
      (95% CI 0.01-0.90), p = 0.019. Other injuries to the lower extremities showed no
      significant difference between the two groups. CONCLUSIONS: Frequent
      neuromuscular exercises prevent severe knee injury in adolescent team handball
      players and should thus be included in the practical routine as well as in the
      education of team coaches.

PMID- 29058023
TI  - Tourniquet application during TKA did not affect the accuracy of implant
      positioning: a randomized clinical trial.
AB  - PURPOSE: The accuracy of the identification of anatomical landmarks with versus
      without tourniquet application and its effect on implant positioning remained
      unknown. Therefore, the hypothesis of the present study was that tourniquet
      application did not affect the accuracy of the reconstruction of the mechanical
      leg alignment, the joint line level, and the patellar height. METHODS: The
      prospective randomized monocentric trial (Clinical-Trials.gov NCT02475603)
      included a total of 86 patients scheduled to undergo primary TKA. The patients
      were allocated to receive TKA with (Group A, n = 43) or without tourniquet (Group
      B, n = 43). The mechanical leg alignment, the joint line level (modified
      Kawamura), and the patellar height (Plateau-patella angle, Insall Salvati index,
      and modified Insall Salvati index) were measured pre- and postoperatively on
      standardized calibrated digital radiographs. Mean, SEM, median, range, and p
      value were calculated for each parameter. RESULTS: There was no statistical
      difference between the groups with regard to demographics, preoperative
      deformity, implant design, and surgical technique (n.s.). The mechanical leg
      alignment, the joint line level, and the patellar height revealed, in both
      groups, similar results pre- and postoperatively (n.s.). CONCLUSION: The
      mechanical leg alignment, the joint line level, and the patellar height could be
      accurately reconstructed with and without tourniquet use. With respect to
      clinically relevant surrogate parameters of implant positioning, TKA can safely
      be performed without a tourniquet. Available data do not support a routine use of
      tourniquet during TKA and might justify a change of the clinical pathway. LEVEL
      OF EVIDENCE: Level I.

PMID- 29058024
TI  - Management of renal transplant urolithiasis: a multicentre study by the French
      Urology Association Transplantation Committee.
AB  - PURPOSE: Urolithiasis is rare among renal transplant recipients and its
      management has not been clearly defined. METHODS: This multicentre retrospective
      study was organised by the Comite de Transplantation de l'Association Francaise
      d'Urologie (French Urology Association transplantation committee). Statistical
      analysis was performed with SPSS 19 software. RESULTS: Ninety-five patients were
      included in this study. Renal transplant urolithiasis was an incidental finding
      in 55% of cases, mostly on a routine follow-up ultrasound examination. One half
      of symptomatic stones were due to urinary tract infection and the other half were
      due to an episode of acute renal failure. The initial management following
      diagnosis of urolithiasis was double J stenting (27%), nephrostomy tube placement
      (21%), or watchful waiting (52%). Definitive management consisted of: watchful
      waiting (48%), extracorporeal lithotripsy (13%), rigid or flexible ureteroscopy
      (26%), percutaneous nephrolithotomy (11%) and surgical pyelotomy (2%). All
      transplants remained functional following treatment of the stone. The main
      limitation is the retrospective design. CONCLUSIONS: The incidence of lithiasis
      could be higher in kidney transplanted patients due to a possible anatomical or
      metabolical abnormalities. The therapeutic management of renal transplant
      urolithiasis appears to be comparable to that of native kidney urolithiasis.

PMID- 29058026
TI  - Invasion pinning in a periodically fragmented habitat.
AB  - Biological invasions can cause great damage to existing ecosystems around the
      world. Most landscapes in which such invasions occur are heterogeneous. To
      evaluate possible management options, we need to understand the interplay between
      local growth conditions and individual movement behaviour. In this paper, we
      present a geometric approach to studying pinning or blocking of a bistable
      travelling wave, using ideas from the theory of symmetric dynamical systems.
      These ideas are exploited to make quantitative predictions about how spatial
      heterogeneities in dispersal and/or reproduction rates contribute to halting
      biological invasion fronts in reaction-diffusion models with an Allee effect. Our
      theoretical predictions are confirmed using numerical simulations, and their
      ecological implications are discussed.

PMID- 29058027
TI  - [Results from the German shoulder- and elbow arthroplasty register (SEPR) :
      Anatomic or reverse shoulder arthroplasty in B2-glenoids?]
AB  - BACKGROUND: Anatomic shoulder arthroplasty in osteoarthritis with biconcave
      glenoid wear results in decreased functional results and a higher rate of early
      glenoid loosening. AIM: The aim of the data analysis of the German shoulder
      arthroplasty register was to clarify whether reverse shoulder arthroplasty can
      provide better functional results and a lower complication rate than anatomic
      arthroplasty in osteoarthritis with biconcave glenoid wear. METHODS: The analysis
      included 1052 completely documented primary implanted arthroplasties with a
      minimum follow-up of 2 years. In 119 cases, a B2-type glenoid was present. Out of
      these cases, 86 were treated with an anatomic shoulder arthroplasty, and in 33
      cases a reverse shoulder arthroplasty was implanted. The mean follow-up was 47.6
      months. RESULTS: The Constant score with its subcategories, as well as the active
      range of movement improved significantly after anatomic and after reverse
      shoulder arthroplasty. DISCUSSION: We observed no difference in functional
      results between both types of arthroplasty; however, reverse arthroplasty showed
      a significant higher revision rate (21.2%) (3% glenoid loosening, 6% prosthetic
      instability) than anatomic shoulder arthroplasty (12.8%) (11.6% glenoid
      loosening, 1.2% prosthetic instability), whereas anatomic shoulder arthroplasty
      showed a higher rate of glenoid loosening. Functional and radiographic results of
      both types of arthroplasty are comparable with the results reported in the
      literature, although our analysis represents results from an implant registry
      (data pertaining to medical care quality).

PMID- 29058028
TI  - The value of contrast-enhanced ultrasound for sentinel lymph node identification
      and characterisation in pre-operative breast cancer patients: A prospective
      study.
AB  - OBJECTIVE: To explore the feasibility of sentinel lymph node (SLN) identification
      by contrast-enhanced ultrasound (CEUS) in pre-operative breast cancer patients
      and the value of enhancement patterns for diagnosing lymph node metastases and
      characterising axillary nodal burden. METHODS: 110 consecutive breast cancer
      patients were enrolled. Before the surgery, microbubbles were injected
      intradermally. The lymphatic drainage pathway was detected to identify the SLNs.
      Blue dye and indocyanine green (ICG) fluorescence were used to trace SLNs during
      the operation. The enhancement patterns of SLNs were recorded and compared with
      the final pathological diagnosis. RESULTS: SLN detection rate was 96.4 % of 110
      patients, 134 SLNs were detected in total. The sensitivity, specificity, positive
      predictive value, negative-predictive value and accuracy of predicting SLNs
      metastases by CEUS enhancement patterns were 100 %, 52.0 %, 43.4 %, 100 % and
      64.9 %, respectively. No metastatic SLNs were presented as homogeneous
      enhancement. Low nodal burden with 0-2 SLN metastases in 92.5 % nodes presented
      as heterogeneous enhancement. No enhancement pattern was proved to be SLN
      metastases in 100 % patients. CONCLUSIONS: CEUS is a feasible approach for SLN
      identification. CEUS enhancement patterns can be helpful in recognising
      metastatic SLNs and nodal burden. KEY POINTS: * CEUS is a feasible approach for
      SLN identification and characterisation. * The enhancement patterns on CEUS can
      be helpful in recognising metastasised SLNs. * Homogeneous enhancement pattern
      has the highest negative-predictive value.

PMID- 29058029
TI  - Increased severity of liver fat content and liver fibrosis in non-alcoholic fatty
      liver disease correlate with epicardial fat volume in type 2 diabetes: A
      prospective study.
AB  - OBJECTIVES: To determine whether severity of non-alcoholic fatty liver disease
      (NAFLD) and liver fibrosis quantitatively assessed in individuals with diabetes
      mellitus (DM)-2 correlate with increased coronary heart disease (CHD) risk using
      non-invasive markers. METHODS: We conducted a single-centre, prospective, cross
      sectional study in 100 consecutive diabetic individuals without known CHD
      recruited between March 2013 and September 2014. History, physical examination,
      serum markers, cardiac computed tomography (CT), magnetic resonance (MR) imaging
      estimated proton density fat fraction (PDFF) and MR elastography (MRE) were
      obtained for 95 participants. Written informed consent was provided.
      Institutional review board approved this study. Spearman rank correlation was
      performed to assess for correlations. Multiple linear regression model determined
      independent predictors of epicardial adipose tissue (EAT) volume. RESULTS: A p
      value < 0.05 determined statistical significance. The EAT volume was higher in
      the NAFLD group, defined as MR-imaging PDFF >= 5 %, compared to the non-NAFLD
      group (126.5 ml (IQR 80.9) versus 85.4 ml (IQR 44.7), p=0.002). MR imaging-PDFF
      correlated with EAT (r=0.42, p < 0.0001). MR imaging-PDFF and liver fibrosis were
      independently associated with EAT. CONCLUSIONS: Higher liver fat content and
      liver fibrosis may portend worse cardiovascular risk in diabetics. KEY POINTS: *
      EAT volume is higher in diabetic individuals with NAFLD. * Liver fat content is
      positively correlated with EAT. * Liver fat content and liver fibrosis were
      independently associated with EAT. * Higher liver fat content and fibrosis may
      adversely affect cardiovascular risk.

PMID- 29058030
TI  - Prevalence of Coronary Artery Disease Risk Factors and Metabolic Syndrome in
      Children with Heart Disease.
AB  - Children with acquired and congenital heart disease (CHD) are increasingly
      surviving to adulthood. Our aim was to determine the prevalence of coronary
      artery disease (CAD) risk factors in children at known risk for early CAD or with
      severe CHD. We recruited children (8-19 years) at risk for early CAD-Kawasaki
      disease (KD, N = 36) and coarctation (69) or severe CHD: > 1 cardiopulmonary
      bypass surgery (60), single ventricle (15), prosthetic valves (13).
      Anthropometric measurements, blood pressure, and fasting lipid data were compared
      with summaries from National Health and Nutrition Examination Survey (NHANES)
      publications (1999-2012). Relative risk (RR) ratios were calculated based on age
      classification and pooled to obtain overall RR. Of 174 subjects, 106 were male
      (61%) and 138 (79%) had CHD. Compared to NHANES data, hypertension and low HDL
      were higher in the study cohort [RR 11.7 (CI 6.34-21.6), p < 0.001; and 1.79 (CI
      1.36-2.35). p < 0.001] and obesity and elevated total cholesterol were lower [RR
      0.59 (CI 0.37-0.96), p = 0.03; and 0.42 (CI 0.19-0.95), p = 0.04]. Elevated non
      HDL was similar between groups. Age category had similar RR for all CAD risk
      factors. Eight subjects had metabolic syndrome. Risk factors were similar between
      KD versus CHD subgroups. Both coarctation and non-coarctation subjects had
      increased RR for hypertension. Hypertension is the most common risk factor for
      children at risk of early CAD and severe CHD. Metabolic syndrome is rare. These
      patients should be screened and treated for hypertension and current
      recommendations for universal lipid screening are adequate for follow-up.

PMID- 29058031
TI  - Predictors and Outcome of Pericardial Effusion After Hematopoietic Stem Cell
      Transplantation in Children.
AB  - Pericardial Effusion (PE) is a potentially life-threatening complication of
      Hematopoietic Cell Transplantation (HCT). Our study aim was to identify
      incidence, risk factors, response to treatment, and outcome of PE after pediatric
      HCT. All patients after HCT at our tertiary center between 2005 and 2010 were
      included. Endpoints were PE development and overall survival. We analyzed patient
      factors, HCT details, and complications and used Cox proportional hazard
      regression modeling to identify predictors for PE. Twelve out of 129 patients
      (9.3%) developed PE. Multivariate analysis demonstrated that young age at HCT was
      a predictor for PE: expressed per year increase in age HR = 0.66 (95% CI 0.46
      0.95, p = 0.03). PE had no impact on overall mortality of HCT. Mild respiratory
      symptoms and vomiting were presenting symptoms for PE. Discontinuation of
      calcineurin inhibitors-with or without pericardiocentesis-was the only effective
      treatment for PE, in contrast to diuretics or increased immunosuppression. Seven
      of 12 PE patients had pericardiocentesis, which was safe and effective in all.
      Pericardial effusion is not rare after HCT, and young age is the only significant
      risk factor. Calcineurin inhibitor toxicity appears to be the primary cause of PE
      after HCT, and discontinuation is effective in the reduction of PE.
      Pericardiocentesis for PE is a safe and effective procedure. Pericardial effusion
      did not have an impact on survival after HCT.

PMID- 29058032
TI  - 2D:4D finger length ratio and radiographic hand osteoarthritis.
AB  - To evaluate the association between the index and ring finger's (2D:4D) length
      ratio with the prevalence and severity of radiographic hand osteoarthritis (OA).
      A population-based sample included 802 males (mean age 46.98 +/- 17.10 years) and
      738 females (mean age 48.65 +/- 16.62 years) who had participated in a Chuvashian
      skeletal aging study. Age, sex, basic demographics, anthropometric data and X
      rays of both hands were acquired. Each hand was visually classified on X-ray as
      either type 1-index finger longer than the ring finger; type 2-index and ring
      finger equal in length; or type 3-index finger shorter than the ring finger. Hand
      OA was defined by the number of affected joints (Kellgren-Lawrence score >= 2) in
      both hands and the sum total of Kellgren-Lawrence scores (total OA score). After
      comparing the OA variables of individuals with different finger length ratio
      types (after adjustment for age and BMI) significant differences were found only
      in females between finger ratio types of the right hand in a number of affected
      joints (F = 3.153, p = 0.043) and finger ratio types of the left (F = 3.330, p =
      0.036) and right (F = 2.397, p = 0.047) hands of the total OA score. Females with
      type 3 ratios had the highest adjusted values of hand OA parameters. We found
      that finger length ratios are associated with hand OA parameters. Females with a
      type 3 finger length pattern showed significantly higher hand OA values than
      those with types 1 and 2.

PMID- 29058033
TI  - Greater rheumatoid arthritis joint improvement with more subjects achieving
      response across improvement categories using novel versus existing ultrasound
      methods.
AB  - We compared the change in joint inflammation and the proportion of subjects
      achieving threshold levels of improvement using the existing methods employing
      ultrasonography on pre-determined joint sites versus novel methods. These novel
      methods select the most affected joints based on (i) ultrasonography-the
      Individualized-Ultrasound (IUS) method, or (ii) ultrasonography and clinical
      joint assessment-the individualized-Composite-Ultrasound (ICUS) method. Mean 3
      month change in total inflammation score (DeltaTIS) and 95% CI was computed for
      each method on 24 RA subjects initiated or escalated on treatment. Individual
      improvement in TIS per subject, calculated as the 3-month DeltaTIS divided by the
      maximum possible TIS score expressed as a percentage, was used to obtain the
      proportion of subjects achieving response across improvement categories. Mean 3
      month DeltaTIS was significantly greater (p values ranging from 0.0003 to 0.0026)
      for novel versus existing methods using 12- and 7-joint approaches. Using 12
      joint approach, percentages of subjects in improvement categories >=5%, >=10%,
      >=15% and >=20% were, respectively, 50, 37.5, 12.5 and 8.3% for IUS; 58.3, 37.5,
      12.5 and 8.3% for ICUS; and 16.7, 0, 0 and 0% for the existing method. Using 7
      joint approach, the respective category percentages were 62.5, 37.5, 25 and 12.5%
      for IUS; 62.5, 41.7, 16.7 and 8.3% for ICUS; and 12.5, 4.2, 4.2 and 0% for the
      existing method. Novel ultrasound methods are more likely to detect improvement
      in joint inflammation, with more subjects achieving response across improvement
      categories, thereby representing a substantial advantage over the existing
      methods. However, this requires confirmation in larger RA cohorts.

PMID- 29058034
TI  - Fourteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT)
      on Cancer Bio-Immunotherapy, Siena, Italy, October 13-15, 2016.

PMID- 29058035
TI  - NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from
      patients with glioma.
AB  - The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor
      associated antigen (TAA)-reactive T-cells from patients with glioma may represent
      a viable source for anticancer-directed cellular therapies. Immunohistochemistry
      was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples)
      protein expression in tumor specimens. T-cells from peripheral blood were
      stimulated with TAAs (synthetic peptides) in IL-2 and IL-7, or using a
      combination of IL-2, IL-15 and IL-21. CD4+ and CD8+ T-cells were tested for
      antigen-specific proliferation by flow cytometry, and IFN-gamma production was
      tested by ELISA. Twenty-eight out of 38 cancer specimens exhibited NY-ESO-1
      protein expression, 2/38 showed a strong universal (4+) NY-ESO-1 staining, and
      9/40 cancer lesions exhibited a strong (4+) staining for survivin. We could
      detect antigen-specific IFN-gamma responses in 25% blood samples for NY-ESO-1 and
      30% for survivin. NY-ESO-1-expanded T-cells recognized naturally processed and
      presented epitopes. NY-ESO-1 or survivin expression in glioma represents viable
      targets for anticancer-directed T-cells for the biological therapy of patients
      with glioma.

PMID- 29058036
TI  - The road less traveled: from genotype to phenotype in flies and humans.
AB  - Understanding how genomic variation gives rise to phenotypic variation is
      essential for elucidating mechanisms of adaptive evolution, plant and animal
      breeding, and precision medicine. However, identifying causal links between DNA
      sequence variants and variation in phenotypes is challenging in human
      populations, due to large blocks of linkage disequilibrium in the genome and
      heterogeneous developmental histories, lifestyles, and social and physical
      environments. Drosophila melanogaster presents a powerful genetic model, since
      linkage disequilibrium decays rapidly, facilitating assignment of causality to
      polymorphisms associated with phenotypic variation, and large numbers of
      individuals can be reared under defined environmental conditions, economically,
      and without regulatory restrictions. The D. melanogaster Genetic Reference Panel
      (DGRP), a population of 205 sequenced, inbred wild-derived flies, has enabled
      genome-wide association studies of morphological, physiological, behavioral, and
      life history traits, and demonstrated that genetic architectures of complex
      traits are highly polygenic, sexually dimorphic, and context dependent with
      extensive sex-, environment-, and genetic background (epistatic) effects. These
      features together with a modular organization of the transcriptome illustrate a
      dynamic integrative genetic architecture for complex traits. The complexity of
      the genetic architectures for complex traits in Drosophila provides important
      caveats for the interpretation of genetic studies in human populations. Aspects
      of the genetic underpinnings of complex traits can be represented as simplified
      gene networks on which human orthologues can be superimposed to provide
      blueprints for subsequent studies on analogous traits in human populations.
      Fundamental principles of the genetic architectures of Drosophila complex traits
      are likely applicable across phyla, from the DGRP to human populations.

PMID- 29058038
TI  - Drug-drug interactions and their harmful effects in hospitalised patients: a
      systematic review and meta-analysis.
AB  - PURPOSE: Drug-drug interactions (DDIs) are often avoidable and, if undetected,
      can lead to patient harm. This review aimed to determine the prevalence of
      potential DDIs (pDDIs), clinically relevant DDIs (DDIs that could lead to
      measurable patient harm, taking into account the patient's individual clinical
      profile) and DDIs that resulted in actual patient harm during hospitalisation.
      METHOD: Four databases were scanned for English papers published from 2000 to
      2016. Papers that reported prevalence of DDIs in the outpatient setting, at
      admission or discharge, involving only specific drugs, or in specific disease
      populations or age groups were excluded. RESULTS: Twenty-seven papers met the
      inclusion criteria and were graded for quality using the Critical Appraisal
      Skills Programme (CASP) cohort study checklist. Ten papers were rated as 'poor',
      14 as 'fair' and only three papers as 'good'. Overall, the meta-analysis revealed
      that 33% of general patients and 67% of intensive care patients experienced a
      pDDI during their hospital stay. It was not possible to determine the prevalence
      of clinically relevant DDIs or DDIs that resulted in actual patient harm as data
      on these categories were limited. Of the very few studies that reported on harm,
      only a small proportion of DDIs were found to have resulted in actual patient
      harm. CONCLUSIONS: Standardisation of DDI definitions and research methods are
      required to allow meaningful prevalence rates to be obtained and compared.
      Studies that go further than measuring pDDIs are critically needed to determine
      the impact of DDIs on patient safety.

PMID- 29058039
TI  - Agreement between manual relaxometry and semi-automated scanner-based multi-echo
      Dixon technique for measuring liver T2* in a pediatric and young adult
      population.
AB  - BACKGROUND: Commercially available 3D multi-echo Dixon (mDixon) sequences provide
      parametric maps of liver T2*, obviating manual curve fitting that is often
      required with conventional gradient recalled echo (GRE)-based multi-echo
      relaxometry, potentially simplifying clinical work flow. OBJECTIVE: The purpose
      of our study was to compare T2* values generated by a 3D mDixon sequence to
      values generated by GRE-based T2* relaxometry with manual curve fitting in a
      pediatric and young adult population. MATERIALS AND METHODS: We reviewed clinical
      MRI exams performed at 1.5T for liver iron content estimation between February
      2015 and June 2016 that included both mDixon and multi-echo GRE pulse sequences.
      We obtained mean T2* measurements based on each sequence by drawing regions of
      interest on each of four axial slices through the mid-liver. We compared mDixon
      based and GRE-based T2* measurements using paired t-tests and assessed agreement
      using single-measure intra-class correlation coefficients and Bland-Altman
      difference plots. RESULTS: One hundred nine patients met inclusion criteria (site
      1=82; site 2=27). Mean age was 12.4+/-5.8 years, and 42 subjects (39%) were
      female. There was no statistically significant difference in mean T2* values for
      the two sequences (pooled means: 11.7+/-11.0 [GRE] vs. 11.7+/-10.9 ms [mDixon];
      P=0.93). There was excellent absolute agreement between sequences (intraclass
      correlation coefficient [ICC]=0.98 for patients at both sites, confidence
      interval [CI]: 0.97-0.98 with mean bias of 0.0 ms [-4.2 ms to +4.2 ms]).
      CONCLUSION: 3D mDixon is accurate for measuring liver T2* and can likely replace
      2D GRE-based relaxometry.

PMID- 29058037
TI  - Epigenetic regulation of agronomical traits in Brassicaceae.
AB  - Epigenetic regulation, covalent modification of DNA and changes in histone
      proteins are closely linked to plant development and stress response through
      flexibly altering the chromatin structure to regulate gene expression. In this
      review, we will illustrate the importance of epigenetic influences by discussing
      three agriculturally important traits of Brassicaceae. (1) Vernalization, an
      acceleration of flowering by prolonged cold exposure regulated through epigenetic
      silencing of a central floral repressor, FLOWERING LOCUS C. This is associated
      with cold-dependent repressive histone mark accumulation, which confers
      competency of consequence vegetative-to-reproductive phase transition. (2) Hybrid
      vigor, in which an F1 hybrid shows superior performance to the parental lines.
      Combination of distinct epigenomes with different DNA methylation states between
      parental lines is important for increase in growth rate in a hybrid progeny. This
      is independent of siRNA-directed DNA methylation but dependent on the chromatin
      remodeler DDM1. (3) Self-incompatibility, a reproductive mating system to prevent
      self-fertilization. This is controlled by the S-locus consisting of SP11 and SRK
      which are responsible for self/non-self recognition. Because self-incompatibility
      in Brassicaceae is sporophytically controlled, there are dominance relationships
      between S haplotypes in the stigma and pollen. The dominance relationships in the
      pollen rely on de novo DNA methylation at the promoter region of a recessive
      allele, which is triggered by siRNA production from a flanking region of a
      dominant allele.

PMID- 29058040
TI  - Pouring out the dirty bathwater without throwing away either the baby or its
      parents: commentary to Saunders et al.

PMID- 29058041
TI  - Dihydromyricetin exerts a rapid antidepressant-like effect in association with
      enhancement of BDNF expression and inhibition of neuroinflammation.
AB  - RATIONALE: Major depressive disorder (MDD) is a highly prevalent illness that
      affects large populations across the world, and increasing evidence suggests that
      neuroinflammation and levels of brain-derived neurotrophic factor (BDNF) are
      closely related to depression. Dihydromyricetin (DHM) is a kind of flavonoid
      natural product that has been reported to display multiple pharmacological
      effects, including anti-inflammatory and anti-oxidative properties, and these may
      contribute to ameliorate MDD. OBJECTIVE: This study investigated the effect of
      DHM on depression-related phenotypes in various experimental animal models.
      METHODS: The antidepressant-like effect of DHM was validated via depression
      related behavioral tests in naive male C57BL/6 mice, as well as in the acute
      lipopolysaccharide-induced mouse model of depression. The chronic unpredicted
      mild stress (CUMS) mouse model of depression was also used to assess the rapid
      antidepressant-like effect of DHM by tail suspension test (TST), forced swimming
      test (FST), locomotor activity, and sucrose preference test (SPT). The expression
      of BDNF and inflammatory factors were determined through Western blotting and
      enzyme-linked immunosorbent assay, respectively. RESULTS: DHM reduced immobility
      time in the TST and FST both in mice and the acute LPS-induced mouse model of
      depression. Seven days of DHM treatment ameliorated depression-related behaviors
      induced by CUMS, whereas similar treatment with the typical antidepressant
      venlafaxine did not. DHM activated the ERK1/2-CREB pathway and increased glycogen
      synthase kinase-3 beta (GSK-3beta) phosphorylation at ser-9, with upregulation of
      BDNF expression, in both hippocampal tissues and cultured hippocampal cells.
      CONCLUSION: The present data indicate that DHM exerts a more rapid antidepressant
      like effect than does a typical antidepressant, in association with enhancement
      of BDNF expression and inhibition of neuroinflammation.

PMID- 29058043
TI  - Synergistic Antimicrobial Activity Between the Broad Spectrum Bacteriocin
      Garvicin KS and Nisin, Farnesol and Polymyxin B Against Gram-Positive and Gram
      Negative Bacteria.
AB  - The increasing emergence of antibiotics resistance is of global concern. Finding
      novel antimicrobial agents and strategies based on synergistic combinations are
      essential to combat resistant bacteria. We evaluated the activity of garvicin KS,
      a new bacteriocin produced by Lactococcus garvieae. The bacteriocin has a broad
      inhibitory spectrum, inhibiting members of all the 19 species of Gram-positive
      bacteria tested. Unlike other bacteriocins from Gram-positive bacteria, garvicin
      KS inhibits Acinetobacter but not other Gram-negative bacteria. Garvicin KS was
      tested in combination with other antimicrobial agents. We demonstrated synergy
      with polymyxin B against Acinetobacter spp. and Escherichia coli, but not against
      Pseudomonas aeruginosa. Similar effects were seen with mixtures of nisin and
      polymyxin B. The synergistic mixtures of all three components caused rapid
      killing and full eradication of Acinetobacter spp. and E. coli. In addition,
      garvicin KS and nisin also acted synergistically against Staphylococcus aureus,
      indicating different in modes of action between the two bacteriocins. Both
      bacteriocins showed synergy with farnesol, and the combination of low
      concentrations of garvicin KS, nisin and farnesol caused rapid eradication of all
      the S. aureus strains tested. Its broad inhibitory spectrum, rapid killing, and
      synergy with other antimicrobials makes garvicin KS a promising antimicrobial.

PMID- 29058044
TI  - Giant angioleiomyoma of the sacral foramina: an unusual location.
AB  - Angioleiomyoma is a benign, vascular smooth muscle tumor originating from the
      tunica media of the vessel wall. In general, it typically arises in the
      cutaneous, subcutaneous tissue or fascia of the lower extremities in middle-aged
      women and is less than 2 cm in diameter. We report an unusual case of an
      angioleiomyoma of the sacral foramina in an 82-year-old man. MRI revealed a well
      defined irregular-shaped deep-seated mass in the sacral foramina, showing
      branching pattern of growth associated with pressure bony erosion of the adjacent
      bones, with isointense to hypointense signal on T2-weighted images. Surgical
      excision was performed and the mass was diagnosed as angioleiomyoma on
      pathological examination. To the best of our knowledge, there has been no report
      of an angioleiomyoma involving the sacral foramina.

PMID- 29058042
TI  - Chronic N-acetylcysteine treatment alleviates acute lipopolysaccharide-induced
      working memory deficit through upregulating caveolin-1 and synaptophysin in mice.
AB  - RATIONALE: Working memory (WM) is a dynamic encoding process and an active
      representation of information over a short time. The ability to guide forthcoming
      behavior would be disrupted if WM was impaired by various factors including
      inflammation, stress, free radicals, and disease states such as schizophrenia.
      However, the mechanism underlying acute working memory impairment remains to be
      defined. OBJECTIVES: In this study, we tested the hypothesis that decreased
      caveolin-1 (Cav-1) and synaptophysin (SYP) accounted for the WM impairment
      challenged with acute intraperitoneally lipopolysaccharide (LPS), which mimicked
      neuroinflammation. Delayed alternation T-maze task (DAT) was used to assess
      working memory of adult male C57BL/6 mice, and western blot and immunostaining
      were used to detect protein expression and distribution in medial prefrontal
      cortex (mPFC) and hippocampus. RESULTS: Our results showed that LPS dose
      dependently induced working memory deficit accompanied by the decrease of Cav-1
      and SYP in mPFC but not hippocampus. In addition, LPS significantly decreased
      protein level of Cav-1 and SYP in neurons by activating microglia cells. More
      important, 2-week N-acetylcysteine (NAC) treatment dose-dependently inhibited LPS
      induced working memory deficit by improving the ability to use Lose-shift but not
      Win-shift strategy and significantly inhibited LPS-induced downregulation of Cav
      1 and SYP in mPFC. CONCLUSIONS: Taken together, our findings demonstrate that
      chronic NAC treatment alleviates acute LPS-induced working memory deficit through
      upregulating Cav-1 and SYP in mice.

PMID- 29058045
TI  - Anterior cervical discectomy and fusion: review and update for radiologists.
AB  - OBJECTIVES: The goals of this article are to describe the various types of
      interbody grafts and anterior cervical plating systems, techniques for optimizing
      evaluation of cervical spine metallic implants on CT and MR imaging, expected
      appearance and complications of ACDF on postoperative imaging and imaging
      assessment of fusion. Optimization for optimizing metal induced artifacts.
      CONCLUSION: Currently, ACDF is the most commonly performed surgical procedure for
      degenerative cervical spine disease. Interbody fusion is performed with bone
      grafts or interbody spacers, and may be supplemented with anterior cervical
      plating. Compressive pathologies at the vertebral body level may be addressed by
      simultaneous corpectomy. Postoperatively, imaging plays an integral role in
      routine screening of asymptomatic individuals, fusion assessment and evaluation
      of complications.

PMID- 29058046
TI  - Hyaline fibromatosis syndrome (juvenile hyaline fibromatosis): whole-body MR
      findings in two siblings with different subcutaneous nodules distribution.
AB  - Hyaline fibromatosis syndrome (juvenile hyaline fibromatosis) is a rare,
      progressive, autosomal recessive disorder whose main hallmark is the deposition
      of amorphous hyaline material in soft tissues, with an evolutionary course and
      health impairment. It may present involvement of subcutaneous or periskeletal
      soft tissue, or may develop as a visceral infiltration entity with poor
      prognosis. Very few radiological data about this inherited condition have been
      reported, due to the extreme rarity of disease. We herein present a case of two
      siblings, affected by different severity of the disease, with different clinical
      features. They were examined by whole-body MR (WBMR) in order to assess different
      lesions localization, to rule out any visceral involvement and any other
      associated anomalies and to define patients' management.

PMID- 29058047
TI  - Recurrent stenosis following carotid artery stenting treated with a drug-eluting
      balloon: a single-center retrospective analysis.
AB  - PURPOSE: Early in-stent restenosis after stent-protected angioplasty of the
      carotid artery (SPAC) is an infrequent, but potentially harmful condition for
      patients with carotid artery disease. METHODS: In our retrospective single-center
      analysis of 176 patients with carotid artery stenting between 2009 and 2015,
      using duplex ultrasound, we detected 9 patients with high-grade carotid artery in
      stent restenosis. All restenosis patients were treated with a drug-eluting
      balloon (DEB) to prevent recurrent neointimal hyperplasia. One patient had
      bilateral carotid artery disease with bilateral in-stent restenosis, and 1
      patient needed repeated DEB treatment 19 months after the first DEB intervention,
      so 11 DEB procedures, in total, were performed. RESULTS: The median time-interval
      between primary carotid artery stenting and first DEB-treatment was 9 months. In
      3 of the 11 interventions, the DEB treatment was assisted by an additional stent.
      One repeat DEB treatment was necessary, and three DEB treatments were followed by
      a secondary stent. No peri-interventional complications (TIA, stroke, or death)
      were observed during or after DEB intervention. Therefore, in the entire group,
      the 1y event-free survival (EFS) was 100%, and the 2y/3y/5y EFS was 83%.
      CONCLUSION: DEB intervention seems to be an effective and safe treatment for
      patients with high-grade in-stent restenosis after SPAC.

PMID- 29058048
TI  - Craniospinal fluid hypotension mimicking arteriovenous fistula on spinal MRI.

PMID- 29058049
TI  - Bayesian estimation and use of high-throughput remote sensing indices for
      quantitative genetic analyses of leaf growth.
AB  - KEY MESSAGE: We develop Bayesian function-valued trait models that mathematically
      isolate genetic mechanisms underlying leaf growth trajectories by factoring out
      genotype-specific differences in photosynthesis. Remote sensing data can be used
      instead of leaf-level physiological measurements. Characterizing the genetic
      basis of traits that vary during ontogeny and affect plant performance is a major
      goal in evolutionary biology and agronomy. Describing genetic programs that
      specifically regulate morphological traits can be complicated by genotypic
      differences in physiological traits. We describe the growth trajectories of
      leaves using novel Bayesian function-valued trait (FVT) modeling approaches in
      Brassica rapa recombinant inbred lines raised in heterogeneous field settings.
      While frequentist approaches estimate parameter values by treating each
      experimental replicate discretely, Bayesian models can utilize information in the
      global dataset, potentially leading to more robust trait estimation. We
      illustrate this principle by estimating growth asymptotes in the face of missing
      data and comparing heritabilities of growth trajectory parameters estimated by
      Bayesian and frequentist approaches. Using pseudo-Bayes factors, we compare the
      performance of an initial Bayesian logistic growth model and a model that
      incorporates carbon assimilation (A max) as a cofactor, thus statistically
      accounting for genotypic differences in carbon resources. We further evaluate two
      remotely sensed spectroradiometric indices, photochemical reflectance (pri2) and
      MERIS Terrestrial Chlorophyll Index (mtci) as covariates in lieu of A max,
      because these two indices were genetically correlated with A max across years and
      treatments yet allow much higher throughput compared to direct leaf-level gas
      exchange measurements. For leaf lengths in uncrowded settings, including A max
      improves model fit over the initial model. The mtci and pri2 indices also
      outperform direct A max measurements. Of particular importance for evolutionary
      biologists and plant breeders, hierarchical Bayesian models estimating FVT
      parameters improve heritabilities compared to frequentist approaches.

PMID- 29058050
TI  - Chromosomes A07 and A05 associated with stable and major QTLs for pod weight and
      size in cultivated peanut (Arachis hypogaea L.).
AB  - KEY MESSAGE: Co-localized intervals and candidate genes were identified for major
      and stable QTLs controlling pod weight and size on chromosomes A07 and A05 in an
      RIL population across four environments. Cultivated peanut (Arachis hypogaea L.)
      is an important legume crops grown in > 100 countries. Hundred-pod weight (HPW)
      is an important yield trait in peanut, but its underlying genetic mechanism was
      not well studied. In this study, a mapping population (Xuhua 13 * Zhonghua 6)
      with 187 recombinant inbred lines (RILs) was developed to map quantitative trait
      loci (QTLs) for HPW together with pod length (PL) and pod width (PW) by both
      unconditional and conditional QTL analyses. A genetic map covering 1756.48 cM was
      constructed with 817 markers. Additive effects, epistatic interactions, and
      genotype-by-environment interactions were analyzed using the phenotyping data
      generated across four environments. Twelve additive QTLs were identified on
      chromosomes A05, A07, and A08 by unconditional analysis, and five of them
      (qPLA07, qPLA05.1, qPWA07, qHPWA07.1, and qHPWA05.2) showed major and stable
      expressions in all environments. Conditional QTL mapping found that PL had
      stronger influences on HPW than PW. Notably, qHPWA07.1, qPLA07, and qPWA07 that
      explained 17.93-43.63% of the phenotypic variations of the three traits were co
      localized in a 5 cM interval (1.48 Mb in physical map) on chromosome A07 with 147
      candidate genes related to catalytic activity and metabolic process. In addition,
      qHPWA05.2 and qPLA05.1 were co-localized with minor QTL qPWA05.2 to a 1.3 cM
      genetic interval (280 kb in physical map) on chromosome A05 with 12 candidate
      genes. This study provides a comprehensive characterization of the genetic
      components controlling pod weight and size as well as candidate QTLs and genes
      for improving pod yield in future peanut breeding.

PMID- 29058051
TI  - Danshen (Salvia miltiorrhiza) protects ovariectomized rats fed with high
      saturated fat-sucrose diet from bone loss.
AB  - : Dietary patterns may interfere with the efficacy of herbal intervention. Our
      results demonstrated the protective effects of Salvia miltiorrhiza aqueous
      extract (SMA) on bone metabolism were influenced by levels of dietary fat and
      sucrose in ovariectomized (OVX) rats through its actions on attenuating lipid
      deposition and oxidative stress in rats. INTRODUCTION: Salvia miltiorrhiza (SM),
      also known as Danshen, has been tested as an osteoporosis treatment in a series
      of small, short human trials that generally report improvements in bone property.
      However, dietary patterns may interfere with the effects of herbal intervention.
      We hypothesized that dietary fat and sucrose levels could influence the effects
      of SM supplementation on bone in estrogen-deficient animals. METHODS: Six-month
      old Sprague-Dawley sham or OVX rats were fed either a low-saturated fat-sucrose
      (LFS, a diet that was similar in composition to normal rat chow) or a high-fat
      sucrose (HFS) diet and OVX rats were treated (8 rats/group) with SM aqueous
      extract (SMA, 600 mg/kg/day), 17beta-estradiol (1 mg/kg/day), or vehicle for 12
      weeks. RESULTS: SMA significantly improved bone properties as revealed by the
      increase in trabecular bone mineral density and decrease in trabecular separation
      at proximal metaphysis of the tibia (PT) in HFS-fed OVX rats, but not in LFS-fed
      OVX rats. SMA greatly reduced lipid deposition and malondialdehyde levels,
      improved the activities of superoxide dismutase, catalase, and glutathione
      peroxidase in the livers of HFS-fed OVX rats. SMA could directly improve the
      proliferation and differentiation in vitro in an H2O2-induced preosteoblast cell
      model by attenuating cellular reactive oxygen species levels. CONCLUSIONS: The
      protective effects of SMA on bone metabolism were influenced by dietary fat and
      sucrose levels in OVX rats. The ability of SMA to reduce bone loss in HFS-fed OVX
      rats was associated with the attenuation of lipid deposition and oxidative stress
      levels.

PMID- 29058052
TI  - Automatic attribution of social coordination information to chasing scenes:
      evidence from mu suppression.
AB  - This study explored whether social coordination information that extends beyond
      individual goals is attributed to impoverished movements produced by simple
      geometric shapes. We manipulated coordination information by presenting two
      chasers and one common target performing coordinated or individual (i.e.,
      uncoordinated) chases, and measured mu rhythms (electroencephalogram oscillations
      within the 8-13 Hz range at sensorimotor regions) related to understanding social
      interactions. We found that although the participants' task was completely
      unrelated to processing chasing motion, mu rhythms were more suppressed for
      coordinated chasing than in the control condition (backward replay for chasing
      motion), and this effect disappeared for uncoordinated chasing. Moreover, mu
      suppression increased with higher post-test ratings of social coordination but
      did not correlate with uncoordinated information. Such effects cannot be
      explained by general attentional involvement, as there was no difference in
      attention-related occipital alpha suppression across conditions. These findings
      are consistent with interpretations of processing coordinated actions, suggesting
      that our visual system can automatically attribute social coordination
      information to motion, at least in chasing scenes.

PMID- 29058053
TI  - Fever control.

PMID- 29058054
TI  - Long-Term High-Dose Resveratrol Supplementation Reduces Bone Mass and Fracture
      Strength in Rats.
AB  - Resveratrol (RSV) is a natural polyphenolic compound. A recent study suggests a
      positive effect on BMD in men; however, the underlying changes in microstructure
      and strength remain unknown. We aimed to investigate the effects of RSV on the
      skeleton in hindlimb-immobilized and non-immobilized rats. Seventy-two female
      Wistar rats were divided into six groups. Two baseline (BSL) groups underwent
      short-term diet intervention for 4 weeks before sacrifice [phytoestrogen
      deficient diet (PD) (BSL + PD) or RSV diet (600 mg/kg body weight/day) (BSL +
      RSV)]. Four groups were injected in the right hindlimb with botulinum toxin (BTX)
      (immobilized) or saline (non-immobilized), and fed either PD diet or RSV diet 4
      weeks pre-injection and 6 weeks post-injection before sacrifice (BTX + PD, BTX +
      RSV, PD, and RSV, respectively). DXA, uCT, dynamic histomorphometry, and
      mechanical tests were performed. Short-term RSV treatment did not affect bone
      parameters, whereas long-term RSV exposure had a consistent negative impact on
      non-immobilized rats (RSV vs. PD); whole femoral aBMD (p = 0.01) and distal
      femoral metaphyseal Tb.N (p = 0.01), Tb.Sp (p = 0.02), and BV/TV (p = 0.07). At
      the femoral mid-diaphysis, RSV increased periosteal resorption (p = 0.01) and
      increased endosteal formation (p = 0.02), while mineralization was unaffected. In
      addition, RSV reduced femoral mid-diaphyseal three-point bending strength (p =
      0.03) and stiffness (p = 0.04). BTX-induced immobilization resulted in
      significant bone loss and reduced bone strength; however, RSV supplementation was
      unable to prevent this. In conclusion, long-term high-dose RSV reduced bone mass
      and fracture strength and did not prevent immobilization-induced bone loss in
      rats.

PMID- 29058055
TI  - Effects of Collagen Crosslinkers on Dentine: A Literature Review.
AB  - This aim of this review is to explore the current research related to
      crosslinking agents used on dentine. A systematic search of publications in
      PubMed and Web of Science databases was performed. Further retrieval was
      conducted using the search terms of specific names of crosslinkers. Reviews,
      conference abstracts, dissertation and theses, non-English articles, studies of
      intrinsic crosslinking of dentine, studies of adhesives without specific
      crosslinker components, studies of crosslinker applications in other collagenous
      tissues or tooth-like structures and irrelevant studies were excluded. Manual
      screening was conducted on the bibliographies of remaining papers to identify
      other relevant articles. One hundred and one articles were included in this
      systematic review and full texts were retrieved. Both synthetic and naturally
      derived crosslinkers have been found to exhibit significant effects in
      biomodification of dentine via their multiple interactions with the dentine
      matrix. A stable matrix network or a durable hybrid layer in dentine bonding
      could be achieved, where the dentine collagen fibrils show improved biochemical
      and biomechanical properties and enzymatic biodegradation is reduced. Although no
      crosslinkers have been tested in clinical trials, extensive research has been
      conducted in laboratory studies to investigate their potential applicability for
      inhibition of demineralisation and/or promotion of remineralisation, caries
      prevention as well as improvement of bonding performance of adhesive systems.
      Further studies are needed to develop the feasibility for clinical use, reduce
      side effects as well as explore mechanisms of action and long-term effectiveness.

PMID- 29058057
TI  - Effects of Lanthanum Carbonate on Coronary Artery Calcification and Cardiac
      Abnormalities After Initiating Hemodialysis.
AB  - It is known that calcium-containing phosphate binders are more closely associated
      with the progression of vascular calcification than non-calcium-containing
      phosphate binders. In this study, we investigated the effect of the non-calcium
      containing phosphate binder, lanthanum carbonate on the progression of coronary
      artery calcification and cardiovascular abnormalities compared to that of calcium
      containing phosphate binder in chronic kidney disease patients during the early
      period after initiating hemodialysis. This was a randomized open-label study in
      which patients were divided into the calcium carbonate or lanthanum carbonate
      group. We evaluated blood samples, coronary artery calcification using high
      resolution computed tomography, and cardiac abnormalities using echocardiography
      prior to and after initiating hemodialysis. Cardiac dimension and systolic
      function were significantly improved in the lanthanum carbonate group compared to
      those in the calcium carbonate group. Although statistically significant
      differences were not observed in all the patients, only among patients with
      moderate coronary artery calcification, the changes in coronary artery
      calcification score at 18 months were significantly smaller in the lanthanum
      carbonate group than those in the calcium carbonate group. The percent change in
      coronary artery calcification at 18 months was significantly correlated with the
      serum fibroblast growth factor 23 levels at 18 months (r = 0.245, P < 0.05). This
      significant correlation was particularly strong in patients with moderate
      coronary artery calcification (r = 0.593, P < 0.001). Our study suggests that
      lanthanum carbonate ameliorates cardiac abnormalities, and may slow coronary
      artery calcification development in patients with moderate coronary artery
      calcification, during the early period following hemodialysis initiation.

PMID- 29058056
TI  - Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size,
      Composition, and Function: Biological Basis for a Gut-Muscle Axis.
AB  - Skeletal muscle is a highly plastic tissue that plays a central role in human
      health and disease. Aging is associated with a decrease in muscle mass and
      function (sarcopenia) that is associated with a loss of independence and reduced
      quality of life. Gut microbiota, the bacteria, archaea, viruses, and eukaryotic
      microbes residing in the gastrointestinal tract are emerging as a potential
      contributor to age-associated muscle decline. Specifically, advancing age is
      characterized by a dysbiosis of gut microbiota that is associated with increased
      intestinal permeability, facilitating the passage of endotoxin and other
      microbial products (e.g., indoxyl sulfate) into the circulation. Upon entering
      the circulation, LPS and other microbial factors promote inflammatory signaling
      and skeletal muscle changes that are hallmarks of the aging muscle phenotype.
      This review will summarize existing literature suggesting cross-talk between gut
      microbiota and skeletal muscle health, with emphasis on the significance of this
      axis for mediating changes in aging skeletal muscle size, composition, and
      function.

PMID- 29058058
TI  - Maternal Early Pregnancy Plasma Concentration of 25-Hydroxyvitamin D and Risk of
      Gestational Diabetes Mellitus.
AB  - We examined whether 25-Hydroxyvitamin D [25(OH) D] concentrations, measured at
      the first prenatal visit, would be associated with risk of gestational diabetes
      mellitus (GDM). From July 2015 to June 2016, consecutive women who admitted to
      the two-obstetrics center in china were included. Relevant data were collected
      between 24 and 28 weeks of gestation, including fasting plasma glucose (FPG) and
      25(OH) D concentrations at the first prenatal visit and the one-step GDM screened
      with 75-g oral glucose tolerance test (OGTT). Blood from women at first prenatal
      visit was available for 827 women and 101 of them developed GDM (12.2%). The GDM
      distribution across the 25(OH) D quartiles ranged between 3.9% (fourth quartile,
      Q4) and 26.1% (first quartile, Q1). The median plasma concentration of 25(OH) D
      at first prenatal visit was significantly lower in women who developed GDM
      compared with those not developed (p < 0.001). In multivariate models comparing
      the 25(OH) D of Q1, second (Q2) and third quartiles (Q3) against the Q4, it
      observed that concentrations of 25(OH) D in Q1 and Q2 were associated with later
      developed GDM, and risk of GDM was increased by 240 and 48%, respectively. The
      women group with combined vitamin D deficiency and obesity had an OR of 4.66 [95%
      CI (2.91-8.15); p < 0.001] for GDM compared to those without vitamin D deficiency
      and obesity. Low 25(OH) D concentrations at the first prenatal visit were
      associated with increased risk of GDM and might be useful in identifying women at
      risk of GDM for performing early prevention strategies.

PMID- 29058059
TI  - Correlates of Level and Loss of Grip Strength in Later Life: Findings from the
      English Longitudinal Study of Ageing and the Hertfordshire Cohort Study.
AB  - Characterisation of grip strength (GS) using isometric dynamometry is central to
      the definition of sarcopenia. Determinants of low GS include: older age, shorter
      stature, low physical activity, poor nutrition, socioeconomic disadvantage and
      multimorbidity. Less is known about risk factors for accelerated loss of GS. We
      investigated determinants of level and 8-year loss of GS in 3703 men and women
      (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four
      hundred and forty-one men and women (aged 59-71 years) who participated in a 10
      year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication.
      Variables were harmonised between cohorts. Change in GS was characterised using
      mixed-effects models in ELSA and a residual change approach in HCS and analysed
      for men and women combined. Men in ELSA and HCS had higher average levels of GS
      at baseline, and accelerated rates of loss, compared with women. In ELSA, older
      age, shorter stature and multimorbidity were correlated with lower level, and
      accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI
      0.00-0.08) standard deviation scores per additional morbidity after multivariable
      adjustment). Socioeconomic disadvantage, low level of physical activity and
      poorer self-reported health were also correlated with low GS level, but not loss
      rate, after multivariable adjustment. Analysis in HCS yielded similar results.
      Our results identify multimorbidity as a modifiable determinant of loss of muscle
      strength in later life, and raise the possibility that developmental influences
      may impact on rate of involutional decline in muscle strength.

PMID- 29058060
TI  - Effects of Seasonal Changes on the Toxic Impacts of Oil Sands Process-Affected
      Water on Daphnia magna.
AB  - Oil sands process-affected water (OSPW), which can be potentially toxic to
      aquatic biota, is a major by-product of bitumen mining in northern Alberta. The
      effects of environmental factors on the toxicity of OSPW are understudied. In the
      present study, the impacts of seasonal changes in water quality on the toxic
      effects of OSPW (1 and 10%) on Daphnia magna was examined. Animals were
      chronically exposed to OSPW under conditions that represented water quality of a
      cold or warm seasonal condition. At each seasonal scenario survival, growth
      (length and mass) and reproduction of exposed D. magna were investigated.
      Survival and length of D. magna were only affected by OSPW in the cold-season
      treatment. Exposure to OSPW reduced the mass of D. magna in both cold and warm
      season scenarios. Daphnia magna in the cold-season treatment did not reproduce or
      produce eggs during the course of the experiment. The results of the present
      study suggest that seasonal changes in water quality may alter the toxicity of
      OSPW on D. magna.

PMID- 29058061
TI  - Current State, Distribution, and Sources of Phthalate Esters and Organophosphate
      Esters in Soils of the Three Gorges Reservoir Region, China.
AB  - Phthalate esters (PAEs) and organophosphate esters (OPEs) were identified and
      quantified in surface soils from farmland and riparian areas of the Three Gorges
      Reservoir (TGR), western China. Generally, the mean values of PAEs and OPEs were
      618 and 266 ng/g dry weight (dw) in farmland soil and 560 and 499 ng/g dw in
      riparian soil, respectively. The occurrence of OPEs should be regarded as a risk
      factor in the TGR region. Analogous spatial distribution patterns for PAEs were
      observed with higher concentrations observed at site WZ in both types of soil,
      which might relate to the anthropogenic activities. The hydrodynamic conditions
      might be important factors contributing to the slightly different spatial
      distribution of OPEs. The concentrations of OPEs in riparian soil exceed those in
      farmland soil at all sampling sites, which could partly be ascribed to the
      complete operation of the TGR. Dibutyl phthalate (DnBP) was the most dominated
      PAEs congener in both types of soil. Of particular note is the elevated
      contribution of tris(methylphenyl) phosphate (TMPP), followed by 2-ethylhexyl
      diphenyl phosphate (EHDPP), accounting for more than 90% of the total OPEs, and
      the shipping or/and the local human activity might be considered as the major
      contributor. The slight differences in PAEs composition of principal components
      might largely attribute to the variety of emission sources in two types of soil.
      The different cluster patterns between two types of soil indicated that the
      anthropogenic activities as well as the full operation of TGR, may play a role.

PMID- 29058062
TI  - Comparison of Dissolved Nickel and Nickel Nanoparticles Toxicity in Larval
      Zebrafish in Terms of Gene Expression and DNA Damage.
AB  - With the use of nanoparticles (NPs) in many industrial activities and consumer
      products, it is important to evaluate the effects of their release into the
      environment. Metal NPs (e.g., Ni-NPs or Cu-NPs) can release metal ions that are
      toxic to aquatic organisms; however, whether the toxicity is from metal ions
      rather than unique "nano-scale" effects of the NPs is unresolved. This research
      investigated Ni-NP toxicity in zebrafish Danio rerio larvae to clarify whether
      toxic effects are attributable to release of Ni ions. First, the acute (96-h
      lethal) toxicity of Ni-NPs was determined in comparison to aqueous Ni in fish
      exposed to Ni(II) by water-soluble NiCl2. Subsequently, sublethal experiments
      with Ni-NPs and Ni(II) were conducted to assess changes in expression of stress
      related genes (mt2, rad51, and p53) by quantitative PCR. Acute toxicity of Ni in
      fish exposed to Ni(II) was higher (96-h LC50 = 32.6 mg/L) than for fish exposed
      to Ni-NPs (96-h LC50 = 122.2 mg/L). Also, DNA strand breaks were higher in Ni(II)
      than Ni-NPs-exposed larvae. Induction of stress-related genes in larvae was
      complex and was not directly related to Ni-NPs and Ni(II) concentration, although
      there was a significant induction in the mt2 and p53 gene of the larvae exposed
      to Ni-NPs and Ni(II) relative to controls. Results indicated that while Ni-NPs
      induced gene expression (presumably by the release of Ni ions), the differences
      in concentration relationships of gene expression between Ni-NPs and Ni(II)
      suggest that factors in addition to the release of Ni ions from Ni-NPs influence
      acute toxicity of Ni-NPs.

PMID- 29058063
TI  - A Novel Scoring System for Diagnosing Acute Mesenteric Ischemia in the Emergency
      Ward: Methodological Issues: Reply.

PMID- 29058065
TI  - International Scholarship Programs of the American College of Surgeons: Expansion
      of the Global Surgical Network.
AB  - BACKGROUND: The American College of Surgeons has always promoted education and
      collaborations with other countries and their scientific organizations. The
      International Guest Scholarship program was established in 1968 to support the
      travel of foreign surgeons to medical Institutions in the USA and Canada. The
      program has grown substantially over time and now includes different categories
      of scholarships and surgeons. The objective of this article is to describe the
      experiences gained by the international scholars who visited US and Canadian
      institutions through these ACS programs. STUDY DESIGN: In order to collect
      information regarding these scholarships from the surgeons who have already
      participated in the program, an Internet-based survey was e-mailed to alumni. The
      surveys were constructed to gather career information on former scholars and to
      analyze the perceived impact of these programs on their careers. RESULTS: Among
      the international scholarships alumni, most are now Fellows of the American
      College of Surgeons. The majority of respondents maintained contact with their
      host surgeons in the USA or Canada; they began or continued research, surgical
      education and surgical quality improvement initiatives in their country of origin
      based upon their experiences as international scholars. Most of the alumni
      reported that the experience they had during the scholarship was inspiring,
      opened their minds and broadened their horizons. CONCLUSIONS: The overall effect
      of ACS international scholarship program should be considered as positive, as 80
      90% of respondent alumni consider their experience very helpful and feel that it
      provided them with opportunities that would not have been possible without it. It
      is incumbent upon the ACS to continue along this path by identifying funding and
      donation sources, as well as enriching the content and goals.

PMID- 29058064
TI  - Less is More: The Impact of Multidisciplinary Thyroid Conference on the Treatment
      of Well-Differentiated Thyroid Carcinoma.
AB  - BACKGROUND: In 2006, a multidisciplinary thyroid conference (MDTC) was
      implemented to better plan management of thyroid cancer patients at our
      institution. This study assessed the clinical impact of a MDTC on radioactive
      iodine (RAI) treatment patterns. METHODS: A prospective database (2003-2014)
      collected patient and tumor characteristics, RAI doses, and tumor recurrences.
      Patients treated with total thyroidectomy for differentiated thyroid carcinoma
      >=1 cm were stratified based on American Thyroid Association (ATA) risk
      classification. RAI regimens were compared before initiation of MDTC (2003-2005,
      n = 88), after establishment of MDTC (2007-2009, n = 95), and after the release
      of 2009 ATA guidelines (2011-2014, n = 181). RAI doses were defined as low (<=75
      mCi), intermediate (76-150 mCi), and high (>150 mCi). RESULTS: There was a
      significant decrease in the number of patients who received high-dose RAI after
      implementation of MDTC compared to before initiation of MDTC in the intermediate
      and high-risk patient groups (p = 0.04 and p < 0.01) without an associated
      increase in tumor recurrence (11 vs. 7%, p = 0.74). On multivariable analysis,
      presentation of a patient at MDTC was a negative predictor for receiving high
      dose RAI (p = 0.002). As might be expected, there was also a significant decrease
      in use of RAI after the 2009 ATA guidelines were issued compared to after
      implementation of MDTC (p < 0.01). CONCLUSION: In conjunction with implementation
      of a thyroid malignancy multidisciplinary conference, we observed significantly
      decreased postoperative dosing of RAI without increased tumor recurrence. The
      2009 ATA guidelines were associated with a further decrease in RAI
      administration. Treatment for patients with thyroid carcinoma is optimized by a
      multidisciplinary approach.

PMID- 29058066
TI  - Transition from Laparoscopic Totally Extraperitoneal Inguinal Hernia Repair to
      Robotic Transabdominal Preperitoneal Inguinal Hernia Repair.

PMID- 29058067
TI  - The Basic Surgical Skills Course in Sub-Saharan Africa: An Observational Study of
      Effectiveness.
AB  - BACKGROUND: The Basic Surgical Skills (BSS) course is a common component of
      postgraduate surgical training programmes in sub-Saharan Africa, but was
      originally designed in a UK context, and its efficacy and relevance have not been
      formally assessed in Africa. METHODS: An observational study was carried out
      during a BSS course delivered to early-stage surgical trainees from Rwanda and
      the Democratic Republic of the Congo. Technical skill in a basic wound closure
      task was assessed in a formal Objective Structured Assessment of Technical Skills
      (OSAT) before and after course completion. Participants completed a pre-course
      questionnaire documenting existing surgical experience and self-perceived
      confidence levels in surgical skills which were to be taught during the course.
      Participants repeated confidence ratings and completed course evaluation
      following course delivery. RESULTS: A cohort of 17 participants had completed a
      pre-course median of 150 Caesarean sections as primary operator. Performance on
      the OSAT improved from a mean of 10.5/17 pre-course to 14.2/17 post-course (mean
      of paired differences 3.7, p < 0.001). Improvements were seen in 15/17 components
      of wound closure. Pre-course, only 47% of candidates were forming hand-tied knots
      correctly and 38% were appropriately crossing hands with each throw, improving to
      88 and 76%, respectively, following the course (p = 0.01 for both components).
      Confidence levels improved significantly in all technical skills taught, and the
      course was assessed as highly relevant by trainees. CONCLUSION: The Basic
      Surgical Skills course is effective in improving the basic surgical technique of
      surgical trainees from sub-Saharan Africa and their confidence in key technical
      skills.

PMID- 29058068
TI  - Clinical Outcomes of Gastric Cancer Patients Who Underwent Proximal or Total
      Gastrectomy: A Propensity Score-Matched Analysis.
AB  - BACKGROUND: Total gastrectomy (TG) and proximal gastrectomy (PG) are used to
      treat upper-third early gastric cancer. To date, no consensus has been reached
      regarding which procedure should be selected. The aim of this study was to
      validate the usefulness of preserving the stomach in early upper-third gastric
      cancer. METHODS: Between 2004 and 2013, 201 patients underwent PG or TG at our
      institution for treatment of upper-third early gastric cancer. According to the
      defined inclusion and exclusion criteria, 192 cases were enrolled in this study.
      One-to-one propensity score matching was performed to compare the outcomes
      between the two groups. RESULTS: The operation time was shorter in the PG group.
      Although no significant difference was observed, the PG group had less bleeding
      and fewer postoperative complications. R0 resection rate was 100%, and no surgery
      related deaths were observed. The frequencies of reflux symptoms and anastomotic
      stenosis were significantly higher in the PG group, but could be controlled by
      balloon dilation and drug therapy. The maintenance rates of body mass index and
      lean body mass were significantly higher in patients who underwent PG than TG.
      The total protein and serum albumin values were higher in the PG group than in
      the TG group and remained statistically superior. CONCLUSION: PG group exhibited
      better perioperative performance. Furthermore, better nutritional results were
      obtained in the PG group. Although the late stenosis and reflux symptoms must be
      addressed, the PG is a preferable surgical procedure for the treatment of early
      proximal gastric cancer.

PMID- 29058070
TI  - Prognostic value of plasma NT-proBNP levels in very old patients with moderate
      renal insufficiency in China.
AB  - BACKGROUND: The N-terminal pro-brain natriuretic peptide (NT-proBNP) has an
      important prognostic value in chronic renal insufficiency; however, most studies
      have been conducted in patients with end-stage renal disease (ESRD). In this
      study we evaluated the prognostic significance of NT-proBNP in very old patients
      with stage 3 chronic kidney disease (CKD) and compared its prognostic value in
      CKD3a versus CKD3b patients. METHODS: Patients (age >=80 years old) hospitalized
      with stage 3 CKD from 2007 to 2010 who were eligible for this prospective study
      underwent follow-up examinations in 2015. The examinations included measurements
      of anthropometric characteristics, blood pressure, plasma NT-proBNP, creatinine,
      and lipids. End-point events were all-cause death and major adverse cardiac
      events (MACEs). RESULTS: A total of 168 patients (mean age 87.4 +/- 2.9 years,
      range 80-99 years) were included in the analysis (CKD3a, n = 117; CKD3b, n = 51).
      The results showed that CKD3b was associated with lower hemoglobin levels, higher
      NT-proBNP levels and a higher rate of hypertension compared with CKD3a. After a
      median follow-up of 3.8 years (interquartile range 1.5-6.1 years), a higher NT
      proBNP level was associated with a higher risk of all-cause death (hazard ratio
      HR 1.986, 95% confidence interval CI 1.276-2.819, p = 0.028) and MACEs (HR 2.872,
      95% CI 1.241-6.644, p = 0.014) after adjusting for age, sex, and traditional risk
      factors; however, a subgroup comparison showed that elevated NT-proBNP levels
      were associated with a higher risk of all-cause death (HR 2.350, 95% CI 1.906
      6.091, p = 0.039) and MACEs (HR 3.025, 95% CI 1.024-8.940, p = 0.045) in CKD3a
      but not CKD3b. CONCLUSION: Levels of NT-proBNP increased with decreased renal
      function in very old patients with stage 3 CKD; therefore, NT-proBNP is an
      independent predictor for all-cause death and MACEs in these patients but has a
      greater prognostic value in CKD3a than in CKD3b.

PMID- 29058069
TI  - Genes linked to species diversity in a sexually dimorphic communication signal in
      electric fish.
AB  - Sexually dimorphic behaviors are often regulated by androgens and estrogens.
      Steroid receptors and metabolism are control points for evolutionary changes in
      sexual dimorphism. Electric communication signals of South American knifefishes
      are a model for understanding the evolution and physiology of sexually dimorphic
      behavior. These signals are regulated by gonadal steroids and controlled by a
      simple neural circuit. Sexual dimorphism of the signals varies across species. We
      used transcriptomics to examine mechanisms for sex differences in electric organ
      discharges (EODs) of two closely related species, Apteronotus leptorhynchus and
      Apteronotus albifrons, with reversed sexual dimorphism in their EODs. The
      pacemaker nucleus (Pn), which controls EOD frequency (EODf), expressed
      transcripts for steroid receptors and metabolizing enzymes, including androgen
      receptors, estrogen receptors, aromatase, and 5alpha-reductase. The Pn expressed
      mRNA for ion channels likely to regulate the high-frequency activity of Pn
      neurons and for neuromodulator and neurotransmitter receptors that may regulate
      EOD modulations used in aggression and courtship. Expression of several ion
      channel genes, including those for Kir3.1 inward-rectifying potassium channels
      and sodium channel beta1 subunits, was sex-biased or correlated with EODf in ways
      consistent with EODf sex differences. Our findings provide a basis for future
      studies to characterize neurogenomic mechanisms by which sex differences evolve.

PMID- 29058071
TI  - [Volumetric analysis of vascularized pigment epithelium detachment in AMD: post
      hoc analysis of the RECOVER study].
AB  - BACKGROUND: The ratio of choroidal neovascularization (CNV) and pigment
      epithelium detachment (PED) represents an important parameter regarding the risk
      of developing a tear of the retinal pigment epithelium (RPE) in patients with
      vascularized PED due to age-related macular degeneration (AMD). METHODS: Within
      the framework of the RECOVER study a total of 29 treatment-naive patients with
      vascularized PED underwent fluorescein angiography (FA), indocyanine green
      angiography (ICGA) and optical coherence tomography (OCT) volume scans. The CNV
      PED ratio was evaluated retrospectively by two independent graders in three ways:
      1) manually based on the en face image of the FA late phase and 2) manually based
      on the en face image of the ICGA late phase. 3) In every OCT scan encompassing
      the PED, the area between the RPE and Bruch's membrane and the CNV area was
      measured and multiplied by the distance between OCT scans in order to determine
      volumetric data of CNV, PED and the serous cavity. RESULTS: The FA and ICGA
      showed a mean serous area of 6.14 +/- 4.21 mm2 (ICGA 5.94 +/- 4.13 mm2), a mean
      CNV area of 3.25 +/- 1.79 mm2 (ICGA 2.84 +/- 1.68 mm2) and a mean PED area of
      9.39 +/- 4.27 mm2 (ICGA 8.79 +/- 4.23 mm2) resulting in a mean two-dimensional
      morphological ratio of 0.35 +/- 0.21 (ICGA 0.32 +/- 0.22). The volumetric
      measurement revealed a mean CNV volume of 0.63 +/- 0.67 mm3, a mean serous volume
      of 3.61 +/- 3.83 mm3 and a mean total PED volume of 4.25 +/- 3.68 mm3. The mean
      three-dimensional morphological ratio was 0.15 +/- 0.29. The difference between
      the two-dimensional ratios of FA (p < 0.0001) and ICGA (p = 0.0004) was
      significant compared to the three-dimensional OCT ratio. CONCLUSION: Assessment
      of the CNV-PED ratio using volumetric OCT measurements is an additional tool to
      the en face modalities FA and ICGA. This seems to be clinically relevant
      regarding the risk stratification of RPE tear development in PED patients and for
      the planning of the treatment regimen.

PMID- 29058072
TI  - Reconstructive surgery for recurrent penile curvature.
AB  - PURPOSE: There are surprisingly few reports about reconstructive surgery for
      severe recurrent/persistent penile curvature (redo-PC). We present our
      experience. METHODS: We reviewed 9 redo-PC cases we treated between 1998 and
      2016. RESULTS: Cases 1-3 and 5 were identified from 111 consecutive hypospadias
      patients we treated between 1998 and 2016 (4/111; 3.6%). Cases 4 and 6-9 had
      initial surgery elsewhere. Initial PC was severe (> 45 degrees ; n = 5), moderate
      (30 degrees -45 degrees ; n = 1), or unknown (n = 3), treated by dorsal plication
      (DP) in 4/9 (cases 1-4), chordectomy in 2/9 (cases 5, 6), and unknown in 3/9
      (cases 7-9); no case had tunica albuginea incision (TAI). Straightening after
      initial surgery was confirmed by artificial erection (AE) in 4/9, not confirmed
      (2/9), and unknown (3/9). Cases 1, 2, 7 and 8 had had previous failed redos.
      Scarring of buccal mucosa used for urethroplasty caused worse PC in cases 7 and
      9. After TAI (n = 6; cases 1, 3-6, and 8) or scar removal with DP (n = 3; cases
      2, 7, and 9), AE confirmed successful straightening in all cases, without
      sequelae after a mean follow-up of 2.6 years. CONCLUSION: TAI was most effective
      for redo-PC surgery. Preoperative AE and examination under anesthesia should be
      used to customize treatment.

PMID- 29058073
TI  - The Rare Complication and Diagnostic Challenges of Pulmonary Eosinophilia in
      Graft versus Host Disease Patients after Hematopoietic Stem Cell Transplantation.
AB  - PURPOSE: Chronic graft versus host disease (cGvHD) is a common complication of
      hematopoietic stem cell transplantation (HSCT). Eosinophilic lung disease is a
      rare poorly understood complication in HSCT patients with cGvHD. These patients
      present similarly to those with Acute Eosinophilic Pneumonia (AEP). The purpose
      of this study is to better elucidate the presentation and potential treatment of
      this phenomenon. METHODS: We reviewed over 170 bronchoscopies in post-HSCT
      patients with respiratory symptoms. Of these, four patients, whose course was
      complicated by cGvHD, presented with respiratory symptoms, diffuse ground-glass
      opacities (GGO) on chest computerized tomography (CT), bronchoalveolar lavage
      (BAL) eosinophilia, and no evidence of infection. The clinical course of these
      patients was reviewed. RESULTS: Despite clinical presentation similar to AEP, not
      all patients had > 25% eosinophils on BAL, one criterion for AEP, however all
      improved with steroids. Steroid initiation was often delayed in favor of empiric
      antibiotics despite negative infectious workup. Several patients had recurrent
      episodes. Regarding possible associations, we examined but found no link between
      particular demographics, reason for HSCT, chemotherapy, immunosuppressants, or
      peripheral eosinophil count and pulmonary eosinophilia in these patients. GGO
      present on initial CT imaging became chronic in several of these patients.
      CONCLUSION: We propose that in post-HSCT patients with GvHD presenting with
      respiratory symptoms, GGO on CT, BAL eosinophilia of > 10%, and negative
      respiratory cultures, an autoimmune eosinophilic process may be occurring.
      Earlier recognition and initiation of corticosteroids in these patients may
      improve their outcomes as an autoimmune diagnosis was often delayed in favor of
      antibiotics.

PMID- 29058074
TI  - Acute coronary syndrome in immigrants and non-immigrants : Results of an Austrian
      prospective pilot study.
AB  - BACKGROUND: There are indications that immigrant patients with acute coronary
      syndrome (ACS) differ in demographic characteristics and clinical presentation
      from non-immigrant patients. The aim of this prospective pilot study was to
      gather clinical and sociodemographic data from patients with ACS and to compare
      immigrants with non-immigrants. METHODS: Included were consecutive patients who
      underwent acute coronary angiography in one cardiological department for ACS from
      September 2011 to September 2013. Information was gathered about age, sex,
      results of the coronary angiography, classical risk factors, socioeconomic
      characteristics as well as ethnicity. Patients who had their place of birth
      outside Austria were specified as immigrants. RESULTS: A total of 100 patients
      (29% female) with a mean age of 60 years (range 34-91 years) were included. Of
      the patients 35 (35%) were immigrants, 12 came from Serbia, 4 from Bosnia, 3 from
      South America, 2 from Germany, 2 from Turkey, 2 from the Czech Republic, 2 from
      Croatia, 2 from Macedonia, and 1 each from Bangladesh, Poland, Romania, Libya,
      Bulgaria and Pakistan. Immigrants tended to be younger on average (56 vs. 62
      years, p = 0.04) and had a two or multivessel disease more often than the non
      immigrants but this difference was not significant (51% vs. 38%, p = 0.29). There
      were no differences between non-immigrants and immigrants concerning the
      classical risk factors for ACS (hypercholesterinemia 60% vs. 69%, nicotine abuse
      51% vs. 60%, hypertension 69% vs. 79%) except diabetes mellitus (15% vs. 37%, p =
      0.02). Sociodemographic data showed differences in education and socioeconomic
      status (SES). Non-immigrants had jobs with high skill level more often than
      immigrants (30% vs. 4%, p = 0.02), although there was no difference between
      immigrants and non-immigrants in the level of high education (9% each); however,
      immigrants more often had low education (31% vs. 11%, p = 0.01) and a monthly
      income below 1000 ? than non-immigrants (41% vs. 14%, p = 0.03). CONCLUSIONS:
      Immigrants with ACS suffered more often from coronary two or multivessel disease
      and diabetes mellitus and were slightly younger than non-immigrants, although
      they did not differ regarding classical risk factors. Results suggest that the
      lower SES of immigrants compared with non-immigrants might contribute to the
      severity of coronary heart disease.

PMID- 29058076
TI  - Medical error and patient safety in the spotlight.

PMID- 29058077
TI  - Does synovialization after anterior cruciate ligament reconstruction have a
      positive effect on functional performance, outcomes scores, stability and muscle
      strength? A 2-year follow-up study after reconstruction.
AB  - BACKGROUND: To investigate the effect of synovialization of graft following
      anterior cruciate ligament reconstruction (ACLR) on functional performance test
      (FPT) and clinical outcomes. METHODS: Eighty-four male patients who underwent
      second-look arthroscopy at 2-year follow-up after unilateral ACLR using hamstring
      autograft were analyzed retrospectively. Patients were categorized by synovial
      coverage into A group (42 subjects, poor synovial coverage) and B group (42
      subjects, good synovial coverage). FPT results, including those of single leg hop
      test (cm) of the involved limb, co-contraction test (s), shuttle run test (s),
      and carioca test (s), were compared between groups. Clinical scores, including
      Lysholm score, International Knee Documentation Committee (IKDC) subjective
      score, and Tegner activity score; stability assessments including Lachman test,
      Pivot-shift test, and side-to-side differences (cm) measured using a KT-2000
      arthrometer were also compared between groups. RESULTS: Based on FPT results, no
      difference was evident between groups. Single leg hop test results were 144.3 +/-
      25.5 in A group and 145.4 +/- 24.7 in B group (P = 0.849). Co-contraction test
      results were 17.1 +/- 2.9 in A group and 16.9 +/- 3.6 in B group (P = 0.827).
      Shuttle run test results were 9.3 +/- 1.9 in A group and 9.3 +/- 1.9 in B group
      (P = 0.935). Carioca test results were 11.4 +/- 2.9 in A group and 10.5 +/- 2.5
      in B group (P = 0.149). Clinical scores and stability assessments did not differ
      between groups (P > 0.05). CONCLUSIONS: Based on functional performance results,
      well-synovialized grafts did not yield better functional performance outcomes
      following ACLR compared to poorly synovialized grafts at 2-year follow-up. The
      same was true of clinical outcomes. Thus, the success of synovialization does not
      improve functional performance and clinical outcomes following ACL reconstruction
      in an all-male population.

PMID- 29058078
TI  - Comminuted inferior pole fracture of patella can be successfully treated with rim
      plate-augmented separate vertical wiring.
AB  - INTRODUCTION: We present the surgical technique of rim-plate-augmented separate
      vertical wiring for comminuted inferior pole fracture of the patella and report
      the clinical outcomes. MATERIALS AND METHODS: Between July 2013 and January 2016,
      13 patients (7 male and 6 female) who were diagnosed with comminuted inferior
      pole fracture of the patella in preoperative computed tomography and underwent a
      minimum of 1 year of follow-up were enrolled in this study. Mean patient age was
      57.7 years (range 28-72 years). All patients underwent open reduction and
      internal fixation by rim-plate-augmented separate vertical wiring. Bony union,
      complications, range of motion and Bostman score were the clinical outcomes.
      RESULTS: Bony union was achieved in all cases at an average of 10 weeks after
      surgery (range 8-12). There was no loss of reduction and fixative failure during
      follow-up. The average range of motion was 127 degrees  (range 120 degrees -130
      degrees ). The mean Bostman score at last follow-up was 29.6 points (range 27-30)
      and graded excellent in 12 patients. CONCLUSION: Rim-plate-augmented separate
      vertical wiring demonstrated secure fixation and favorable clinical outcomes.
      This study provides evidence for its effectiveness as a fixation method for
      treating displaced, comminuted inferior pole fracture of the patella.

PMID- 29058080
TI  - Sixty years of animal biometeorology.
AB  - Animal biometeorology (insects excluded) has been part of the International
      Journal of Biometeorology since its inception in 1958. Over the first 60 years of
      the journal, 480 animal biometeorology papers were published. Thus, approximately
      14% of published papers dealt with animals. Over the first 60 years, data from
      more than 50 animal species was presented, with the lead authors coming from 48
      countries. The two most common species used in animal papers between 1957 and
      2016 were cattle (109 papers: 22.7% of all animal papers) and rats (96 papers:
      20.0% of all animal papers). Although cattle and rats dominated, the species in
      the most cited paper (240 citations) was chickens, followed by bird migration
      (155 citations), and general livestock (118 citations). Overall, five papers
      exceeded 100 citations, and a further two exceeded 200 citations. In the last
      decade, 126 animal papers were published (26% of all animal papers). Many of
      these papers had a focus on livestock production in developing countries
      especially Brazil.

PMID- 29058079
TI  - Extended trochanteric osteotomy (ETO) fixation for femoral stem revision in
      periprosthetic fractures: Dall-Miles plate versus cables.
AB  - BACKGROUND: Extended trochanteric osteotomy (ETO) is a well-established surgical
      technique used for femoral stem retrieval in revision hip arthroplasty
      procedures. Fixation of ETO is commonly achieved through wire, cable or cable
      plate fixation. No evidence exists to date to suggest which method is superior
      when used in an acute traumatic setting. METHODS: Thirty cases of acute
      periprosthetic fracture requiring femoral stem revision with an ETO were
      identified over a 10-year period. Each case had a loose femoral prosthesis which
      was revised using an ETO approach. Nineteen of these were fixed using cables
      only, and 11 were fixed using a cable-plate construct. Radiographic outcomes
      measured included greater trochanter migration, osteolysis, union, time to union
      and overall success using the Beals and Tower classification. Clinical outcomes
      were assessed using the modified Harris Hip Score. RESULTS: Twenty-three
      Vancouver B/C-type fractures were identified. The remaining seven consisted of
      other fracture types with a loose femoral stem requiring revision through ETO.
      Mean follow-up was 32 months in the cable group and 12 months in the cable-plate
      group. The cable-plate construct performed better than cables alone. Mean
      migration rates were 1.7 mm lower in the cable-plate group (p < 0.05). Beals and
      Tower classification of radiographic outcomes was significantly better in the
      cable-plate group (p < 0.01). Modified Harris Hip Scores were better in this
      group also (p < 0.05). CONCLUSION: When utilising an ETO approach for femoral
      stem revision in acute periprosthetic fractures, superior clinical and
      radiographic outcomes can be achieved if fixation involves a cable-plate system
      instead of cables only.

PMID- 29058081
TI  - Assessment of the climatic potential for tourism in Iran through biometeorology
      clustering.
AB  - This study presents a spatiotemporal analysis of bioclimatic comfort conditions
      for Iran using mean daily meteorological data from 1995 to 2014, analyzed through
      Physiological Equivalent Temperature (PET) index and Universal Thermal Climate
      Index (UTCI) indices, and bioclimatic clustering. The results of this study
      demonstrate that due to the climate variability across Iran during the year,
      there is at any point in time a location with climatic condition suitable for
      tourism. Mean values demonstrate maxima in bioclimatic comfort indices for the
      country in late winter and spring and minima for summer. Seven statistically
      significant clusters in bioclimatic indices were identified. Comparing these with
      clustering performed on PET and UTCI, the maximum overlaps between the two
      indices. In the following, the outputs of this research showed that most
      appropriate bioclimatic clustering for Iran includes seven clusters. These
      clustering locations according to climatic suitability for tourism provide a
      valuable contribution to tourism management in the country, particularly through
      marketing destinations to maximize tourist flow.

PMID- 29058082
TI  - Forensic differentiation between peripheral and menstrual blood in cases of
      alleged sexual assault-validating an immunochromatographic multiplex assay for
      simultaneous detection of human hemoglobin and D-dimer.
AB  - Sexual assault is a serious offense and identification of body fluids originating
      from sexual activity has been a crucial aspect of forensic investigations for a
      long time. While reliable tests for the detection of semen and saliva have been
      successfully implemented into forensic laboratories, the detection of other body
      fluids, such as vaginal or menstrual fluid, is more challenging. Especially, the
      discrimination between peripheral and menstrual blood can be highly relevant for
      police investigations because it provides potential evidence regarding the issue
      of consent. We report the forensic validation of an immunochromatographic test
      that allows for such discrimination in forensic stains, the SERATEC PMB test, and
      its performance on real casework samples. The PMB test is a duplex test combining
      human hemoglobin and D-dimer detection and was developed for the identification
      of blood and menstrual fluid, both at the crime scene and in the laboratory. The
      results of this study showed that the duplex D-dimer/hemoglobin assay reliably
      detects the presence of human hemoglobin and identifies samples containing
      menstrual fluid by detecting the presence of D-dimers. The method distinguished
      between menstrual and peripheral blood in a swab from a historical artifact and
      in real casework samples of alleged sexual assaults. Results show that the
      development of the new duplex test is a substantial progress towards analyzing
      and interpreting evidence from sexual assault cases.

PMID- 29058083
TI  - Exercise program design considerations for head and neck cancer survivors.
AB  - The present study aimed to establish exercise preferences, barriers, and
      perceived benefits among head and neck cancer survivors, as well as their level
      of interest in participating in an exercise program. Patients treated for primary
      squamous cell carcinoma of the head and neck between 2010 and 2014 were
      identified from the hospital database and sent a postal questionnaire pack to
      establish exercise preferences, barriers, perceived benefits, current physical
      activity levels, and quality of life. A postal reminder was sent to non
      responders 4 weeks later. The survey comprised 1021 eligible patients of which
      437 (43%) responded [74% male, median (interquartile range) age, 66 (60-73)
      years]. Of the respondents, 30% said 'Yes' they would be interested in
      participating in an exercise program and 34% said 'Maybe'. The most common
      exercise preferences were a frequency of three times per week, moderate
      intensity, and 15-29 min per bout. The most popular exercise types were walking
      (68%), flexibility exercises (35%), water activites/swimming (33%), cycling
      (31%), and weight machines (19%). Home (55%), outdoors (46%) and health club/gym
      (33%) were the most common preferred choices for where to regularly exercise.
      Percieved exercise benefits relating to improved physical attributes were
      commonly cited, whereas potential social and work-related benefits were less well
      acknowledged. The most commonly cited exercise barriers were dry mouth or throat
      (40%), fatigue (37%), shortness of breath (30%), muscle weakness (28%) difficulty
      swallowing (25%), and shoulder weakness and pain (24%). The present findings
      inform the design of exercise programs for head and neck cancer survivors.

PMID- 29058084
TI  - Clinical evaluation of coronally advanced flap with or without platelet-rich
      fibrin for the treatment of multiple gingival recessions.
AB  - OBJECTIVES: The aim of this randomized, controlled study was to assess the
      clinical effect of platelet-rich fibrin (PRF) in combination with coronally
      advanced flap (CAF) on root coverage, esthetics, and patient satisfaction when
      compared to CAF alone for the treatment of multiple Miller class I recessions.
      MATERIALS AND METHODS: A total of 24 patients with 52 Miller class I multiple
      recessions >= 3 mm were included and divided into CAF + PRF and CAF groups. At
      baseline and 12 months after surgery, recession height (RH), keratinized tissue
      height, gingival thickness (GT), and mean and complete defect coverage were
      evaluated. Patient satisfaction and root coverage esthetic scores were also
      assessed. RESULTS: Baseline RH in CAF + PRF and CAF groups was 3.15 +/- 0.24 and
      3.36 +/- 0.34 mm, respectively. Intragroup comparisons revealed significant
      differences at 12 months for all parameters (p < 0.05). RH reduction was 2.75 +/-
      0.33 and 2.51 +/- 0.33 mm (mean root coverage of 88.36 and 74.63%) in the CAF +
      PRF and CAF groups, respectively. Intergroup differences were found to be
      significant for GT gain (p < 0.05). CONCLUSIONS: The additional use of PRF
      membrane did not provide additional benefits in terms of root coverage outcomes
      compared with CAF alone. The use of PRF membranes increased tissue thickness
      significantly.

PMID- 29058085
TI  - Stercoral perforation proximal to the stapled anastomosis after low anterior
      resection with an intraluminal device.
AB  - Stercoral perforation of the colon is a rare phenomenon and a potential life
      threatening condition requiring acute intervention. A little more than 200 cases
      have been described to date. The mechanism is not completely understood. In this
      short communication, we present three patients with a colon perforation proximal
      to the anastomosis, similar to a stercoral perforation, following colorectal
      cancer resection with application of an intraluminal device, the C-seal.

PMID- 29058086
TI  - Influence of attention and bolus volume on brain organization during swallowing.
AB  - It has been shown that swallowing involves certain attentional and cognitive
      resources which, when disrupted can influence swallowing function with in
      dysphagic patient. However, there are still open questions regarding the
      influence of attention and cognitive demands on brain activity during swallowing.
      In order to understand how brain regions responsible for attention influence
      brain activity during swallowing, we compared brain organization during no
      distraction swallowing and swallowing with distraction. Fifteen healthy male
      adults participated in the data collection process. Participants performed ten 1
      ml, ten 5 ml, and ten 10 ml water swallows under both no-distraction conditions
      and during distraction while EEG signals were recorded. After standard pre
      processing of the EEG signals, brain networks were formed using the time
      frequency based synchrony measure. The brain networks formed were then compared
      between the two sets of conditions. Results showed that there are differences in
      the Delta, Theta, Alpha, Beta, and Gamma frequency bands between no-distraction
      swallowing and swallowing with distraction. Differences in the Delta and Theta
      frequency bands can be attributed to changes in subliminal processes, while
      changes in the Alpha and Beta frequency bands are directly associated with the
      various levels of attention and cognitive demands during swallowing process, and
      changes in the Gamma frequency band are due to changes in motor activity.
      Furthermore, we showed that variations in bolus volume influenced the swallowing
      brain networks in the Delta, Theta, Alpha, Beta, and Gamma frequency bands.
      Changes in the Delta, Theta, and Alpha frequency bands are due to sensory
      perturbations evoked by the various bolus volumes. Changes in the Beta frequency
      band are due to reallocation of cognitive demands, while changes in the Gamma
      frequency band are due to changes in motor activity produced by variations in
      bolus volume. These findings could potentially lead to the development of better
      understanding of the nature of dysphagia and various rehabilitation strategies
      for patients with neurogenic dysphagia who have altered attention or impaired
      cognitive functions.

PMID- 29058087
TI  - Contrasting effects of adaptation to a visuomotor rotation on explicit and
      implicit measures of sensory coupling.
AB  - We previously investigated sensory coupling of the sensed positions of cursor and
      hand in a cursor-control task and found differential characteristics of implicit
      and explicit measures of the bias of sensed hand position toward the position of
      the cursor. The present study further tested whether adaptation to a visuomotor
      rotation differentially affects these two measures. Participants made center-out
      reaching movements to remembered targets while looking at a rotated feedback
      cursor. After sets of practice trials with constant (adaptation condition) or
      random (control condition) visuomotor rotations, test trials served to assess
      sensory coupling. In these trials, participants judged the position of the hand
      at the end of the center-out movement, and the deviation of these judgments from
      the physical hand positions served as explicit measure of the bias of sensed hand
      position toward the position of the cursor, whereas the implicit measure was
      based on the direction of the return movement. The results showed that inter
      individual variability of explicitly assessed biases of sensed hand position
      toward the cursor position was less in the adaptation condition than in the
      control condition. Conversely, no such changes were observed for the implicit
      measure of the bias of sensed hand position, revealing contrasting effects of
      adaptation on the explicit and implicit measures. These results suggest that
      biases of explicitly sensed hand position reflect sensory coupling of neural
      representations that are altered by visuomotor adaptation. In contrast, biases of
      implicitly sensed hand position reflect sensory coupling of neural
      representations that are unaffected by adaptation.

PMID- 29058088
TI  - Structures and stabilities of naturally occurring cyclodextrins: a theoretical
      study of symmetrical conformers.
AB  - A molecular modeling study of symmetrical conformers of alpha-, beta-, and gamma
      cyclodextrins in the gas and aqueous phases was carried out using the M06-2X
      density functional method, with SMD employed as an implicit solvation model.
      Eight symmetrical conformers were found for each cyclodextrin. Values of
      geometrical parameters obtained from the modeling study were found to agree well
      with those obtained from X-ray diffraction structures. A vibrational analysis
      using harmonic frequencies was performed to determine thermodynamic quantities.
      The GIAO method was applied to determine proton and carbon-13 NMR chemical
      shifts, which were then compared with corresponding chemical shifts reported in
      the literature. Hydrogen-bonding patterns were analyzed using geometrical
      descriptors, and quantum chemical topology was explored by QTAIM analysis. The
      results of this study indicated that four of the eight conformers studied for
      each cyclodextrin are the most populated in aqueous solution. These results
      provide the foundations for future studies of host-guest complexes involving
      these cyclodextrins. Graphical abstract deltaDeltaGsolvation: variation of free
      Gibss energy of solvation.

PMID- 29058090
TI  - ICP management in patients suffering from traumatic brain injury: a systematic
      review of randomized controlled trials.
AB  - BACKGROUND: Severe traumatic brain injury (sTBI) is a major cause of morbidity
      and mortality. Intracranial pressure (ICP) monitoring and management form the
      cornerstone of treatment paradigms for sTBI in developed countries. We examine
      the available randomized controlled trial (RCT) data on the impact of ICP
      management on clinical outcomes after sTBI. METHODS: A systematic review of the
      literature on ICP management following sTBI was performed to identify pertinent
      RCT articles. RESULTS: We identified six RCT articles that examined whether ICP
      monitoring, decompressive craniectomy, or barbiturate coma improved clinical
      outcomes after sTBI. These studies support (1) the utility of ICP monitoring in
      the management of sTBI patients and (2) craniectomy and barbiturate coma as
      effective methods for the management of intracranial hypertension secondary to
      sTBI. However, despite adequate ICP control in sTBI patients, a significant
      proportion of surviving patients remain severely disabled. CONCLUSIONS: If one
      sets the bar at the level of functional independence, then the RCT data raises
      questions pertaining to the utility of decompressive craniectomy and barbiturate
      coma in the setting of sTBI.

PMID- 29058091
TI  - Disturbance of CT perfusion within 24 h after onset is associated with WFNS grade
      but not development of DCI in patients with aneurysmal SAH.
AB  - BACKGROUND: Delayed cerebral ischemia (DCI) is a serious complication following
      aneurysmal SAH (aSAH) and remains a leading cause of morbidity and mortality. We
      investigated whether data from CT perfusion (CTP) within 24 h after onset are
      associated with DCI and its outcome. METHODS: We retrospectively examined plain
      CT, CTP, and CT angiography (CTA) of aSAH patients on arrival. We measured the
      average mean transit time (aMTT) and compared it with several clinical factors,
      such as the age, WFNS grade, Fisher group, delayed cerebral infarction, cerebral
      vasospasm, and modified Rankin scale (mRS), at 1 month. Regions of interest
      (ROIs) were quantitatively determined in cortical and two basal ganglia areas.
      RESULTS: Delayed cerebral ischemia (DCI) developed in 11 patients and cerebral
      vasospasm in 28 patients out of a total of 86 aSAH patients scanned within 24 h
      after onset. The average MTT was correlated with the WFNS grade (p = 0.000), but
      not mRS (p = 0.128), age (p = 0.759), DCI (p = 0.669), or cerebral vasospasm (p =
      0.306). On the other hand, DCI was associated with the Fisher group (p = 0.0056),
      mRS (p = 0.0052), and cerebral vasospasm (p = 0.000). Moreover, there were no
      significant differences in the average MTT within 24 h after onset between
      territories with and without DCI, or between patients with and without DCI.
      CONCLUSIONS: The current findings suggest that disturbance of CT perfusion soon
      after the onset is associated with the WFNS grade but not with the development of
      DCI. Delayed cerebral ischemia may be solely caused by cerebral vasospasm due to
      a clot in the cistern, but not associated with early brain injury.

PMID- 29058089
TI  - Evidence-based treatment of neurogenic orthostatic hypotension and related
      symptoms.
AB  - Neurogenic orthostatic hypotension, postprandial hypotension and exercise-induced
      hypotension are common features of cardiovascular autonomic failure. Despite the
      serious impact on patient's quality of life, evidence-based guidelines for non
      pharmacological and pharmacological management are lacking at present. Here, we
      provide a systematic review of the literature on therapeutic options for
      neurogenic orthostatic hypotension and related symptoms with evidence-based
      recommendations according to the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE). Patient's education and non-pharmacological
      measures remain essential, with strong recommendation for use of abdominal
      binders. Based on quality of evidence and safety issues, midodrine and droxidopa
      reach a strong recommendation level for pharmacological treatment of neurogenic
      orthostatic hypotension. In selected cases, a range of alternative agents can be
      considered (fludrocortisone, pyridostigmine, yohimbine, atomoxetine, fluoxetine,
      ergot alkaloids, ephedrine, phenylpropanolamine, octreotide, indomethacin,
      ibuprofen, caffeine, methylphenidate and desmopressin), though recommendation
      strength is weak and quality of evidence is low (atomoxetine, octreotide) or very
      low (fludrocortisone, pyridostigmine, yohimbine, fluoxetine, ergot alkaloids,
      ephedrine, phenylpropanolamine, indomethacin, ibuprofen, caffeine,
      methylphenidate and desmopressin). In case of severe postprandial hypotension,
      acarbose and octreotide are recommended (strong recommendation, moderate level of
      evidence). Alternatively, voglibose or caffeine, for which a weak recommendation
      is available, may be useful.

PMID- 29058092
TI  - Anthrax immune globulin improves hemodynamics and survival during B. anthracis
      toxin-induced shock in canines receiving titrated fluid and vasopressor support.
AB  - BACKGROUND: Although anthrax immune globulin (AIG) improved survival in
      antibiotic-treated Bacillus anthracis-challenged animal models, whether it adds
      to the benefit of conventional hemodynamic support for B. anthracis toxin
      associated shock is unknown. METHODS: We therefore tested AIG in sedated,
      mechanically ventilated canines challenged with 24-h B. anthracis lethal and
      edema toxin infusions and supported for 96 h with a previously demonstrated
      protective regimen of titrated normal saline and norepinephrine. RESULTS:
      Compared to controls, proportional survival (%) was increased with AIG treatment
      started 4 h before (33 vs. 100%, n = 6 each) or 2 h (17 vs. 86%, n = 6 and 7
      respectively) or 5 h (0 vs. 67%, n = 3 each) after the start of toxin (p <= 0.05)
      and overall [3 survivors of 15 controls (20%) vs. 14 of 16 AIG animals (88%); p =
      0.006]. Averaged across treatment times, AIG increased blood pressure at 48 h and
      decreased norepinephrine requirements at 72 h (p <= 0.02), increased left
      ventricular ejection fraction at 48 and 72 h (p <= 0.02), and increased urine
      output and decreased net fluid balance at 72 and 96 h (p <= 0.04). AIG also
      reduced acidosis and renal and hepatic injury markers between 24 and 96 h.
      CONCLUSIONS: These findings further support AIG's potential benefit for patients
      with B. anthracis infection and developing toxin-associated shock.

PMID- 29058093
TI  - Transcriptome analysis reveals the genetic basis underlying the biosynthesis of
      volatile oil, gingerols, and diarylheptanoids in ginger (Zingiber officinale
      Rosc.).
AB  - BACKGROUND: Ginger (Zingiber officinale Rosc.) is a popular flavoring that widely
      used in Asian, and the volatile oil in ginger rhizomes adds a special fragrance
      and taste to foods. The bioactive compounds in ginger, such as gingerols,
      diarylheptanoids, and flavonoids, are of significant value to human health
      because of their anticancer, anti-oxidant, and anti-inflammatory properties.
      However, as a non-model plant, knowledge about the genome sequences of ginger is
      extremely limited, and this limits molecular studies on this plant. In this
      study, de novo transcriptome sequencing was performed to investigate the
      expression of genes associated with the biosynthesis of major bioactive compounds
      in matured ginger rhizome (MG), young ginger rhizome (YG), and fibrous roots of
      ginger (FR). RESULTS: A total of 361,876 unigenes were generated by de novo
      assembly. The expression of genes involved in the pathways responsible for the
      biosynthesis of major bioactive compounds differed between tissues (MG, YG, and
      FR). Two pathways that give rise to volatile oil, gingerols, and
      diarylheptanoids, the "terpenoid backbone biosynthesis" and "stilbenoid,
      diarylheptanoid and gingerol biosynthesis" pathways, were significantly enriched
      (adjusted P value < 0.05) for differentially expressed genes (DEGs) (FDR < 0.005)
      both between the FR and YG libraries, and the FR and MG libraries. Most of the
      unigenes mapped in these two pathways, including curcumin synthase,
      phenylpropanoylacetyl-CoA synthase, trans-cinnamate 4-monooxygenase, and 4
      hydroxy-3-methylbut-2-en-1-yl diphosphate synthase, were expressed to a
      significantly higher level (log2 (fold-change) >= 1) in FR than in YG or MG.
      CONCLUSION: This study provides the first insight into the biosynthesis of
      bioactive compounds in ginger at a molecular level and provides valuable genome
      resources for future molecular studies on ginger. Moreover, our results establish
      that bioactive compounds in ginger may predominantly synthesized in the root and
      then transported to rhizomes, where they accumulate.

PMID- 29058094
TI  - Impact of an insoluble surfactant on the thresholds of evaporative Benard
      Marangoni instability under air.
AB  - It is known that the addition of an insoluble surfactant to a Benard-Marangoni
      (BM) layer heated from below or cooled from above can give rise to a
      supplementary, oscillatory mode of instability. Here the objective is to see how
      exactly this plays out in the framework of a recently studied and experimentally
      tested case of a non-long-wavelength BM instability driven by diffusion-limited
      evaporation into air in isothermal surroundings. Linear stability analysis is
      accomplished within a now standard reduction to a one-sided model. In the absence
      of surfactant, we just recover the classical Pearson problem, albeit with an
      evaporation-specific wavenumber-dependent Biot number potentially attaining large
      values for strongly volatile liquids. Adding a surfactant not only sharply
      stabilizes the monotonic Pearson-like mode, but also leads to a more dangerous
      oscillatory mode, a parametric study of which is here undertaken. Although
      slanted towards the evaporative case, the present study is also of interest from
      the general viewpoint of the Pearson problem + an insoluble surfactant, the
      results for which are scarce in the literature without being obscured by further
      effects. In particular, an asymptotic analysis based on small interfacial Lewis
      numbers (diffusion coefficients) is undertaken near the codimension-2 point.

PMID- 29058095
TI  - Potentiation and Block of ASIC1a by Memantine.
AB  - Acid-sensing ion channels (ASICs) are modulated by various classes of ligands,
      including the recently described hydrophobic monoamines, which inhibit and
      potentiate ASICs in a subunit-specific manner. In particular, memantine inhibits
      ASIC1a and potentiates ASIC2a homomers. The aim of the present work was to
      characterize action mechanism of memantine on recombinant ASIC1a expressed in CHO
      (Chinese hamster ovary) cells. We have demonstrated that effect of memantine on
      ASIC1a strongly depends on membrane voltage, conditioning pH value and
      application protocol. When applied simultaneously with activating acidification
      at hyperpolarized voltages, memantine caused the strongest inhibition.
      Surprisingly, application of memantine between ASIC1a activations at zero voltage
      caused significant potentiation. Analysis of the data suggests that memantine
      produces two separate effects, voltage-dependent open-channel block and shift of
      steady-state desensitization curve to more acidic values. Putative binding sites
      are discussed based on the computer docking of memantine to the acidic pocket and
      the pore region.

PMID- 29058096
TI  - Craniofacial height in relation to cross-sectional maxillary and mandibular
      morphology.
AB  - BACKGROUND: In order to gain a better understanding of how growth of the alveolar
      bone is linked to the vertical development of the face, the purpose of this study
      was to investigate if there is an association between the cross-sectional
      morphology of the maxillary and mandibular bodies with the craniofacial height,
      using images from cone beam computed tomography (CBCT). METHODS: From 450 pre
      treatment CBCT scans, 180 were selected to be included in the study. Lateral head
      images were generated from the CBCT scans and were used to categorise subjects
      into three groups based on their vertical craniofacial height. Cross-sectional
      images from CBCT volumes were reformatted of the maxillary and mandibular bodies
      at five locations in the maxilla and five in the mandible. Each image was
      measured at one height and two width measurements. Statistical analysis performed
      was the one-way analysis of variance with a Tukey post hoc test. A significance
      level of 5% was used in all comparisons. RESULTS: Patients with large vertical
      craniofacial height had a significantly higher cross-sectional area both in the
      maxilla and in the mandible. In the same group, the cross-sectional area was
      significantly thinner in the mandible compared with the other two groups,
      especially in the anterior region. CONCLUSIONS: This study further highlights the
      close relationship between craniofacial height and alveolar bone dimensions and
      contributes with important knowledge for planning and follow-up of comprehensive
      dental- and orthodontic treatments.

PMID- 29058099
TI  - Gynephilic Men's Self-Reported and Genital Sexual Responses to Relationship
      Context Cues.
AB  - The current study examined men's sexual responses to relationship context.
      Chivers and Timmers (2012) previously reported that heterosexual men's genital
      and self-reported sexual arousal varied by gender but not relationship context,
      suggesting that gender cues are more salient determinants of sexual response than
      relationship context cues for men. Those analyses were, however, significantly
      underpowered to detect relationship context effects (n = 9). The current study
      utilized the same paradigm as Chivers and Timmers' study, exposing a larger
      sample of heterosexual men (n = 26) to audio narratives describing sexual
      interactions that varied by partner gender (man, woman) and relationship context
      (stranger, friend, long-term relationship), and observing effects on genital and
      self-reported sexual response. Results indicated that men's genital response to
      relationship context cues mirrored those previously reported for heterosexual
      women (Chivers & Timmers, 2012); heterosexual men demonstrated less genital
      response to the friend than to the stranger or long-term relationship conditions.
      No significant effect of relationship context was found for men's self-reported
      sexual arousal. These data suggest that, in addition to gender cues, relationship
      cues may also be an important determinant of men's genital sexual responses.

PMID- 29058097
TI  - Regional differences in advanced gastric cancer: exploratory analyses of the
      AVAGAST placebo arm.
AB  - BACKGROUND: AVAGAST was an international, randomized, placebo-controlled phase
      III study of chemotherapy with or without bevacizumab as first-line therapy for
      patients with advanced gastric cancer. We performed exploratory analyses to
      evaluate regional differences observed in the trial. METHODS: Analyses were
      performed in the placebo plus chemotherapy arm (intention-to-treat population).
      Chemotherapy was cisplatin 80 mg/m2 for six cycles plus capecitabine (1000 mg/m2
      orally bid days 1-14) or 5-fluorouracil (800 mg/m2/day continuous IV infusion
      days 1-5) every 3 weeks until disease progression or unacceptable toxicity.
      RESULTS: Overall, 387 patients were assigned to placebo plus chemotherapy
      (eastern Europe/South America, n = 118; USA/western Europe, n = 81; Korea/other
      Asia, n = 94; Japan, n = 94). At baseline, poor performance status, liver
      metastases, and larger tumors were most frequent in eastern Europe/South America
      and least frequent in Japan. Patients received subsequent chemotherapy after
      disease progression as follows: eastern Europe/South America (14%); USA/western
      Europe (37%); Korea/other Asia (61%); and Japan (77%). Hazard ratios for overall
      survival versus USA/western Europe were 1.47 (95% CI, 1.09-1.99) for eastern
      Europe/South America, 0.91 (95% CI, 0.67-1.25) for Korea/other Asia, and 0.87
      (95% CI, 0.64-1.19) for Japan. CONCLUSIONS: Regional differences in the
      healthcare environment may have contributed to the differences in overall
      survival observed in the AVAGAST study.

PMID- 29058098
TI  - Osteomyelitis of the lower extremity: pathophysiology, imaging, and
      classification, with an emphasis on diabetic foot infection.
AB  - Osteomyelitis is inflammation of the bone caused by an infectious organism, and
      is a difficult clinical problem. The pathophysiology, imaging, and classification
      of osteomyelitis are challenging, varying with the age of the patient (child
      versus adult), the chronicity of the infection (acute versus chronic), and the
      route of spread (hematogenous versus contiguous focus), as well as the immune and
      vascular status of the patient and affected region. The two most common
      classification schemes are those of Lew and Waldvogel, and Cierny and Mader.
      Brodie's abscess is seen in subacute osteomyelitis, while sequestrum, involucrum,
      and cloaca are inter-related entities of chronic osteomyelitis. Imaging workup of
      suspected osteomyelitis should begin with radiographs, although MRI is the most
      accurate imaging test. Three patterns of T1 signal change have been described in
      the setting of suspected osteomyelitis including confluent intramedullary, hazy
      reticular, and subcortical. The confluent intramedullary pattern is most
      associated with osteomyelitis, while hazy reticular is rarely associated with
      hematogenous osteomyelitis, and subcortical is not associated with osteomyelitis.
      It can be challenging to differentiate neuropathic arthropathy from
      osteomyelitis. Osteomyelitis tends to involve a single bone subjacent to an ulcer
      or sinus tract. In contrast, neuropathic arthropathy tends to involve multiple
      bones of the midfoot. Subchondral cystic change, thin rim enhancement of a joint
      effusion, and the presence of intra-articular bodies are more indicative of a
      neuropathic joint without infection. Biopsy can play an important role in
      diagnosis and treatment of osteomyelitis.

PMID- 29058100
TI  - Human Mating Theory, Migration, and Marital Dissolution.
AB  - Marriage dissolution has been extensively analyzed in the last few decades,
      looking for the determinants of this well-known phenomenon, but so far the
      relationship between female migration and marriage dissolution does not seem to
      have been thoroughly investigated. This work aimed to analyze the correlation
      between marriage dissolution and migration, which might bias the sex ratio within
      a given society, introducing new social and cultural values. Considering the
      Regions of Italy between 2002 and 2007 (i.e., 120 observations), several multiple
      regression models (OLS) were presented to test the proposed hypothesis, applying
      the robust option. The dependent variable of our empirical investigation was a
      marriage dissolution index, while the key explanatory variables were a sex ratio
      and several female rates. Based on the results, the hypothesis of a statistically
      significant positive relation between the influx of female immigrants and
      household dissolution could be supported (i.e., p < .01). However, not all
      migrating women are the same and a different impact is foreseeable according to
      the nature of this influx. Indeed, given a 1% influx of unmarried foreign
      females, increasing the sex ratio within society, marital dissolutions grow by
      5381 for every 100,000 marriages. In the case of a 1% influx of Italian unmarried
      females, marital dissolutions grew by 3173 for every 100,000 marriages.
      Therefore, females could have specific sexual, social and cultural
      characteristics, which might be able to increase (or decrease) the probability of
      men being driven to sexual infidelity, thus leading to a higher frequency of
      marriage dissolutions.

PMID- 29058102
TI  - Procaspase-activating compound-1 induces apoptosis in Trypanosoma cruzi.
AB  - Some therapeutics for parasitic, cardiac and neurological diseases activate
      apoptosis. Therefore, the study of apoptotic proteins in pathogenic organisms is
      relevant. However, the molecular mechanism of apoptosis in unicellular organisms
      remain elusive, despite morphological evidence of its occurrence. In Trypanosoma
      cruzi, the causative agent of Chagas disease, metacaspase 3 (TcMCA3), seems to
      have a key role in parasite apoptosis. Accordingly, this work provides data
      concerning TcMCA3 regulation through its interaction with procaspase-activating
      compound 1 (PAC-1), a procaspase 3 activator. Indeed, PAC-1 reduced T. cruzi
      epimastigote viability with an IC50 of 14.12 uM and induced loss of mitochondrial
      potential and exposure of phosphatidylserine, features of the apoptotic process.
      Notwithstanding, those PAC-1-inducible effects were not conserved in metacyclic
      trypomastigotes. Moreover, PAC-1 reduced the viability of mammalian cells with a
      greater IC50 (25.70 uM) compared to T. cruzi epimastigotes, indicating distinct
      modes of binding between caspases and metacaspases. To shed light on the
      selectivity of metacaspases and caspases, we determined the structural features
      related to the PAC-1 binding sites in both types of proteins. These data are
      important for improving the understanding of the apoptosis pathway in T. cruzi so
      that TcMCA3 could be better targeted with future pharmaceuticals.

PMID- 29058103
TI  - Effects of transgenic expression of Brevibacterium linens methionine gamma lyase
      (MGL) on accumulation of Tylenchulus semipenetrans and key aminoacid contents in
      Carrizo citrange.
AB  - KEY MESSAGE: Carrizo transgenic plants overexpressing methionine-gamma-lyase
      produced dimethyl sulfide. The transgenic plants displayed more resistance to
      nematode attacks (Tylenculus semipenetrans) and may represent an innovative
      strategy for nematode control. Tylenchulus semipenetrans is a nematode pest of
      many citrus varieties that causes extensive damage to commercial crops worldwide.
      Carrizo citrange vr. (Citrus sinensis L. Usb * Poncirus trifoliate L. Raf) plants
      overexpressing Brevibacterium linens methionine-gamma-lyase (BlMGL) produced the
      sulfur volatile compound dimethyl sulfide (DMS). The aim of this work was to
      determine if transgenic citrus plants expressing BlMGL showed increased tolerance
      to T. semipenetrans infestation and to determine the effect on the content of key
      amino acids. While transgenic lines emitted dimethyl sulfide from leaves and
      roots, no sulfur-containing volatiles were detectable in wild-type Carrizo in the
      same tissues. Significant changes detected some key amino acids from leaves of
      transgenic plants such as aspartate, lysine, glycine, leucine and threonine with
      no changes in the amounts of methionine and alpha-ketobutyrate. In roots only
      glycine showed significant changes across all transgenic lines in comparison to
      wild-type plants. Transgenic plants expressing BlMGL and emitting DMS had less T.
      semipenetrans aggregation and more biomass than infected WT control plants,
      indicating that they may represent an innovative management alternative to
      pesticide/nematicide-based remedies.

PMID- 29058101
TI  - DOCK8 Deficiency Presenting as an IPEX-Like Disorder.
AB  - PURPOSE: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal
      recessive-combined immunodeficiency whose clinical spectra include recurrent
      infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food
      allergies. Here, we report on patients with loss of function DOCK8 mutations with
      profound immune dysregulation suggestive of an immune dysregulation,
      polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder. METHODS:
      Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein
      expression were evaluated by flow cytometry. T regulatory (Treg) cells were
      isolated by cell sorting, and their suppressive activity was analyzed by flow
      cytometry. Gene mutational analysis was performed by whole-exome and Sanger
      sequencing. RESULTS: Patient 1 (P1) presented at 10 months of age with chronic
      severe diarrhea and active colitis in the absence of an infectious trigger,
      severe eczema with elevated serum IgE, and autoimmune hemolytic anemia,
      suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a
      homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1
      (c.1498C>T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8
      nonsense mutation, presented with eczema and recurrent ear infections in early
      infancy, and she developed persistent diarrhea by 3 years of age. Patient P3
      presented with lymphoproliferation, severe eczema with allergic dysregulation,
      and chronic diarrhea with colitis. She harbored a homozygous loss of function
      DOCK8 mutation (c.2402 -1G->A). Treg cell function was severely compromised by
      both DOCK8 mutations. CONCLUSION: DOCK8 deficiency may present severe immune
      dysregulation with features that may overlap with those of IPEX and other IPEX
      like disorders.

PMID- 29058106
TI  - Line of fire - what happened at the Wantabadgery seige?
AB  - A gunfight between police and a gang of men led by the self-styled "Captain
      Moonlite", a.k.a. George Scott, occurred on 16th November 1879 at a farmhouse
      near Wantabadgery Station in the colony of New South Wales. The skirmish resulted
      in the deaths of two bushrangers and one police officer. As a result, Captain
      Moonlite and Thomas Rogan were hung in Sydney's Darlinghurst Gaol on 20 January
      1880 for the murder of Constable Edward Webb-Bowen. Culpability for firing the
      fatal shot, however, has remained a source of controversy. Information obtained
      from an analysis of historical records was used to guide an archeological
      excavation at the scene of the shooting in which Terrestrial Laser Scanning (TLS)
      technology was employed to produce a digital (3D) terrain model of the siege
      location. Utilizing the terrain model, the relative positions of Moonlite, Webb
      Bowen, and the other gang members were established with possible projectile
      trajectories plotted. This, in combination with inquest evidence from a gun maker
      and the medical practitioner who examined Constable Webb-Bowen's wound, indicates
      that the most likely shooter was Gus Warnicke, aged 15 years, the youngest member
      of the gang, who was also killed in the exchange of fire.

PMID- 29058105
TI  - Disentangling the Relations between Social Identity and Prosocial and Antisocial
      Behavior in Competitive Youth Sport.
AB  - The social identities formed through membership on extracurricular activity
      groups may contribute to the frequency with which youth engage in prosocial and
      antisocial behavior. However, researchers have yet to disentangle the individual-
      and group-level processes social identification effects operate through; sex and
      perceived norms may also moderate such effects. Thus, we investigated the
      hierarchical and conditional relations between three dimensions of social
      identity (i.e., ingroup ties, cognitive centrality, ingroup affect) and prosocial
      and antisocial behavior in youth ice hockey players (N = 376; 33% female).
      Multilevel analyses demonstrated antisocial teammate and opponent behavior were
      predicted by cognitive centrality at the team level. Further, prosocial teammate
      behavior was predicted by cognitive centrality and ingroup ties at the individual
      level. Also, perceived norms for prosocial teammate behavior moderated the
      relations between ingroup ties, cognitive centrality, and ingroup affect and
      prosocial teammate behaviour. Finally, sex moderated the relations between
      cognitive centrality/ingroup affect and antisocial opponent behavior. This work
      demonstrates the multilevel and conditional nature of how social identity
      dimensions relate to youth prosocial and antisocial behavior.

PMID- 29058107
TI  - ZIKA virus isolated from mosquitoes: a field and laboratory investigation in
      China, 2016.
AB  - A field investigation of arboviruses was conducted in Dejiang, Guizhou Province
      in the summer of 2016. A total of 8,795 mosquitoes, belonging to four species of
      three genera, and 1,300 midges were collected. The mosquito samples were
      identified on site according to their morphology, and the pooled samples were
      ground and centrifuged in the laboratory. The supernatant was incubated with
      mosquito tissue culture cells (C6/36) and mammalian cells (BHK-21) for virus
      isolation. The results indicated that 40% (3,540/8,795) were Anopheles sinensis,
      30% (2,700/8,795) were Culex pipiens quinquefasciatus, and 29% (2,530/8,795) were
      Armigeres subbalbeatus. Furthermore, a total of eight virus isolates were
      obtained, and genome sequencing revealed two Zika viruses (ZIKVs) isolated from
      Culex pipiens quinquefasciatus and Armigeres subbalbeatus, respectively; three
      Japanese encephalitis viruses (JEVs) isolated from Culex pipiens
      quinquefasciatus; two Banna viruses (BAVs) isolated from Culex pipiens
      quinquefasciatus and Anopheles sinensis, respectively; and one densovirus (DNV)
      isolated from Culex pipiens quinquefasciatus. The ZIKVs isolated from the Culex
      pipiens quinquefasciatus and Armigeres subbalbeatus mosquitoes represent the
      first ZIKV isolates in mainland China. This discovery presents new challenges for
      the prevention and control of ZIKV in China, and prompts international
      cooperation on this global issue.

PMID- 29058109
TI  - A 3D Hermite-based multiscale local active contour method with elliptical shape
      constraints for segmentation of cardiac MR and CT volumes.
AB  - Analysis of cardiac images is a fundamental task to diagnose heart problems. Left
      ventricle (LV) is one of the most important heart structures used for cardiac
      evaluation. In this work, we propose a novel 3D hierarchical multiscale
      segmentation method based on a local active contour (AC) model and the Hermite
      transform (HT) for LV analysis in cardiac magnetic resonance (MR) and computed
      tomography (CT) volumes in short axis view. Features such as directional edges,
      texture, and intensities are analyzed using the multiscale HT space. A local AC
      model is configured using the HT coefficients and geometrical constraints. The
      endocardial and epicardial boundaries are used for evaluation. Segmentation of
      the endocardium is controlled using elliptical shape constraints. The final
      endocardial shape is used to define the geometrical constraints for segmentation
      of the epicardium. We follow the assumption that epicardial and endocardial
      shapes are similar in volumes with short axis view. An initialization scheme
      based on a fuzzy C-means algorithm and mathematical morphology was designed. The
      algorithm performance was evaluated using cardiac MR and CT volumes in short axis
      view demonstrating the feasibility of the proposed method.

PMID- 29058108
TI  - Pre-admission TSH levels predict long-term mortality in adults treated for
      hypothyroidism.
AB  - CONTEXT: Limited data is available regarding the association between pre
      admission thyroid function and prognosis of hospitalized patients treated for
      hypothyroidism. OBJECTIVE: Evaluate an association between thyroid stimulating
      hormone (TSH) levels and mortality in hospitalized levothyroxine-treated
      patients. DESIGN AND SETTING: Observational data of patients admitted to medical
      wards between 2011 and 2013. TSH levels obtained up to 180 days prior to
      admission were stratified as follows: low (<=0.5 mIU/L), normal (0.5-5 mIU/L),
      high (>5 mIU/L). PATIENTS: Patients aged 60-80 years with available thyroid
      function tests were matched with controls without hypothyroidism. MAIN OUTCOME:
      All-cause mortality up to 66-months following discharge. RESULTS: One thousand
      and fifty seven patients (73% females, mean (SD) age 71 +/- 6 years) were matched
      with controls without hypothyroidism. Mean hospital stay and in-hospital
      mortality were not different between groups. Mortality risk at the end-of-follow
      up was 41% (438/1057) and 37% (392/1057) for patients with and without
      hypothyroidism (p < 0.05). TSH levels were classified as follows: low, 84
      patients (8%); normal, 667 patients (63%); high, 306 patients (29%). Length of
      hospitalization and in-hospital mortality were not different between TSH
      categories. Mortality risk at the end-of-follow-up was 30, 39, and 50% with low,
      normal and elevated TSH, respectively. Adjusted hazard ratio (95% CI) of
      mortality at the end-of-follow-up was of 2.2 (1.2-3.8) for high vs. low TSH
      levels, and 1.4 (1.1-1.9) for high vs. normal TSH levels. CONCLUSION: In treated
      hypothyroid adult patients, increased TSH up to 6 months prior to admission is
      associated with increased mortality. Treatment should aim at achieving
      euthyroidism to improve survival.

PMID- 29058111
TI  - The effects of muscle blood flow restriction during running training on measures
      of aerobic capacity and run time to exhaustion.
AB  - PURPOSE: Training with blood flow restriction (BFR) is known to enhance muscle
      mass and strength during resistance training activities. However, little is known
      about the BFR effects during aerobic training. This investigation examines the
      effects of running training performed with or without BFR on physiology and
      performance. METHOD: Sixteen subjects (age 24.9 +/- 6.9 years, height 172.9 +/-
      7.8 cm, weight 75.1 +/- 13.8 kg) were assigned to a BFR or control (CON) group
      for eight sessions of training. Before and after training, subjects completed an
      incremental test to determine peak running velocity (PRV) maximal oxygen uptake
      ([Formula: see text]) and running economy (RE), followed by a time to exhaustion
      run (TTE) performed at PRV. Training for both groups consisted of progressively
      increasing volumes of 30-s repetitions completed at 80% of PRV. RESULTS: The BFR
      and CON groups reported gains (6.3 +/- 3.5 vs 4.0 +/- 3.3%) in [Formula: see
      text] following training with only trivial (ES = 0.18) differences between
      groups. Similarly, PRV and incremental test time increased in both training
      groups with a small (ES ~ 0.3) additional enhancement in favour of the BFR group.
      Running economy improved in the BFR group but not in CON (ES = 0.4). TTE also
      increased in both BFR (27 +/- 9%) and CON groups (17 +/- 6%) with a small (ES =
      0.31) additional benefit in favour of the BFR group. CONCLUSIONS: Using BFR
      during training appears to confer small but potentially worthwhile improvements
      in RE, PRV and TTE measures. The improvements following BFR training are likely
      due to muscular rather than cardiovascular function.

PMID- 29058110
TI  - Computational prediction of the effects of the intra-aortic balloon pump on heart
      failure with valvular regurgitation using a 3D cardiac electromechanical model.
AB  - Intra-aortic balloon pump (IABP) is normally contraindicated in significant
      aortic regurgitation (AR). It causes and aggravates pre-existing AR while
      performing well in the event of mitral regurgitation (MR). Indirect parameters,
      such as the mean systolic pressure, product of heart rate and peak systolic
      pressure, and pressure-volume are used to quantify the effect of IABP on
      ventricular workload. However, to date, no studies have directly quantified the
      reduction in workload with IABP. The goal of this study is to examine the effect
      of IABP therapy on ventricular mechanics under valvular insufficiency by using a
      computational model of the heart. For this purpose, the 3D electromechanical
      model of the failing ventricles used in previous studies was coupled with a
      lumped parameter model of valvular regurgitation and the IABP-treated vascular
      system. The IABP therapy was disturbed in terms of reducing the myocardial
      tension generation and contractile ATP consumption by valvular regurgitation,
      particularly in the AR condition. The IABP worsened the problem of ventricular
      expansion induced as a result of the regurgitated blood volume during the
      diastole under the AR condition. The IABP reduced the LV stroke work in the AR,
      MR, and no regurgitation conditions. Therefore, the IABP helped the ventricle to
      pump blood and reduced the ventricular workload. In conclusion, the IABP
      partially performed its role in the MR condition. However, it was disturbed by
      the AR and worsened the cardiovascular responses that followed the AR. Therefore,
      this study computationally proved the reason for the clinical contraindication of
      IABP in AR patients.

PMID- 29058112
TI  - Glutamine supplementation reduces markers of intestinal permeability during
      running in the heat in a dose-dependent manner.
AB  - PURPOSE: To examine the dose-response effects of acute glutamine supplementation
      on markers of gastrointestinal (GI) permeability, damage and, secondary,
      subjective symptoms of GI discomfort in response to running in the heat. METHODS:
      Ten recreationally active males completed a total of four exercise trials; a
      placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg-1 of fat-free
      mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60
      min treadmill run at 70% of [Formula: see text] in an environmental chamber set
      at 30  degrees C. GI permeability was measured using ratio of lactulose to
      rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding
      protein (I-FABP) concentrations were determined pre and post exercise. Subjective
      GI symptoms were assessed 45 min and 24 h post-exercise. RESULTS: Relative to
      placebo, L:R was likely lower following 0.25 g kg-1 (mean difference: - 0.023; +/
      0.021) and 0.5 g kg-1 (- 0.019; +/- 0.019) and very likely following 0.9 g kg- 1
      (- 0.034; +/- 0.024). GI symptoms were typically low and there was no effect of
      supplementation. DISCUSSION: Acute oral glutamine consumption attenuates GI
      permeability relative to placebo even at lower doses of 0.25 g kg-1, although
      larger doses may be more effective. It remains unclear if this will lead to
      reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit
      from acute glutamine supplementation prior to exercise in order to maintain
      gastrointestinal integrity.

PMID- 29058114
TI  - Reporting myocardial flow reserve with PET. Ready or not, here it is! But walk
      before you fly!

PMID- 29058113
TI  - Voluntary activation and variability during maximal dynamic contractions with
      aging.
AB  - Whether reduced supraspinal activation contributes to age-related reductions in
      maximal torque during dynamic contractions is not known. The purpose was to
      determine whether there are age differences in voluntary activation and its
      variability when assessed with stimulation at the motor cortex and the muscle
      during maximal isometric, concentric, and eccentric contractions. Thirty young
      (23.6 +/- 4.1 years) and 31 old (69.0 +/- 5.2 years) adults performed maximal
      isometric, shortening (concentric) and lengthening (eccentric) contractions with
      the elbow flexor muscles. Maximal isometric contractions were performed at 90
      degrees  elbow flexion and dynamic contractions at a velocity of 60 degrees /s.
      Voluntary activation was assessed by superimposing an evoked contraction with
      transcranial magnetic stimulation (TMS) or with electrical stimulation over the
      muscle during maximal voluntary contractions (MVCs). Old adults had lower MVC
      torque during isometric (- 17.9%), concentric (- 19.7%), and eccentric (- 9.9%)
      contractions than young adults, with less of an age difference for eccentric
      contractions. Voluntary activation was similar between the three contraction
      types when assessed with TMS and electrical stimulation, with no age group
      differences. Old adults, however, were more variable in voluntary activation than
      young (standard deviation 0.99 +/- 0.47% vs. 0.73 +/- 0.43%, respectively) to
      both the motor cortex and muscle, and had greater coactivation of the antagonist
      muscles during dynamic contractions. Thus, the average voluntary activation to
      the motor cortex and muscle did not differ with aging; however, supraspinal
      activation was more variable during maximal dynamic and isometric contractions in
      the old adults. Lower predictability of voluntary activation may indicate
      subclinical changes in the central nervous system with advanced aging.

PMID- 29058115
TI  - Adolescents at ultra-high risk of psychosis in Italian neuropsychiatry services:
      prevalence, psychopathology and transition rate.
AB  - Studies in adolescents on ultra-high risk (UHR) and basic symptoms (BS) criteria
      for psychosis prediction are scarce. In Italy, early interventions in psychosis
      are less widespread than in other European countries. In the present study, we
      (1) assessed the clinical relevance of a UHR diagnosis [according to the
      comprehensive assessment of at-risk mental states (CAARMS) criteria] to promote
      the implementation of specific services for UHR adolescents into the Italian
      health care system; (2) described severity of positive, negative, general, and
      basic symptoms in UHR adolescents compared to adolescents with first-episode
      psychosis (FEP) and non-UHR adolescents (i.e., individuals who did not meet
      CAARMS criteria for UHR or FEP); and (3) investigated the predictive validity of
      UHR criteria in relation to BS criteria. Seventy-nine adolescents (aged 13-18
      years) were assessed with the CAARMS, the positive and negative syndrome scale
      (PANSS), and the schizophrenia proneness instrument, child and youth version (SPI
      CY). Both UHR (n = 25) and FEP (n = 11) had significantly higher PANSS subscale
      scores compared to non-UHR (n = 43). UHR had significantly lower PANSS-positive
      symptom scores than FEP, but similar global functioning and PANSS-negative
      symptoms and general psychopathology scores. Compared to non-UHR, both FEP and
      UHR had more severe thought and perception BS disturbances, and significantly
      more often met BS criteria. After 12 months, 2 of 20 (10%) UHR had transitioned
      to psychosis. They also met both BS criteria. Given the uncertain outcome of UHR
      adolescents, future research is needed to determine whether the combined
      assessment of BS with UHR symptoms can improve the accuracy of psychosis
      prediction in adolescence.

PMID- 29058118
TI  - The Dawning of the Ethics of Environmental Robots.
AB  - Environmental scientists and engineers have been exploring research and
      monitoring applications of robotics, as well as exploring ways of integrating
      robotics into ecosystems to aid in responses to accelerating environmental,
      climatic, and biodiversity changes. These emerging applications of robots and
      other autonomous technologies present novel ethical and practical challenges.
      Yet, the critical applications of robots for environmental research, engineering,
      protection and remediation have received next to no attention in the ethics of
      robotics literature to date. This paper seeks to fill that void, and promote the
      study of environmental robotics. It provides key resources for further critical
      examination of the issues environmental robots present by explaining and
      differentiating the sorts of environmental robotics that exist to date and
      identifying unique conceptual, ethical, and practical issues they present.

PMID- 29058117
TI  - Recapitulating cortical development with organoid culture in vitro and modeling
      abnormal spindle-like (ASPM related primary) microcephaly disease.
AB  - The development of a cerebral organoid culture in vitro offers an opportunity to
      generate human brain-like organs to investigate mechanisms of human disease that
      are specific to the neurogenesis of radial glial (RG) and outer radial glial
      (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the
      developing neocortex. Modeling neuronal progenitors and the organization that
      produces mature subcortical neuron subtypes during early stages of development is
      essential for studying human brain developmental diseases. Several previous
      efforts have shown to grow neural organoid in culture dishes successfully,
      however we demonstrate a new paradigm that recapitulates neocortical development
      process with VZ, OSVZ formation and the lamination organization of cortical layer
      structure. In addition, using patient-specific induced pluripotent stem cells
      (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we
      demonstrate neurogenesis defects result in defective neuronal activity in patient
      organoids, suggesting a new strategy to study human developmental diseases in
      central nerve system.

PMID- 29058116
TI  - Longitudinal associations of social cognition and substance use in childhood and
      early adolescence: findings from the Avon Longitudinal Study of Parents and
      Children.
AB  - Substance use is associated with impaired social cognition. Experimental studies
      have shown that acute intoxication of alcohol, tobacco, and cannabis decreases
      the performance in non-verbal, social communication and theory of mind tasks.
      However, in epidemiological studies the temporal direction of this association
      has gone relatively unstudied. We investigated both directions of association
      within an adolescent birth cohort: the association of social cognition with
      subsequent substance use, and the association of early substance use with
      subsequent social cognition. We used data from the Avon Longitudinal Study of
      Parents and Children, a UK birth cohort. Logistic regression indicated that poor
      childhood non-verbal communication was associated with decreased odds of
      adolescent alcohol (OR 0.70, 95% 0.54-0.91), tobacco (OR 0.62, 95% CI 0.47-0.83),
      and cannabis use (OR 0.62, 95% CI 0.46-0.83). Early adolescent substance use was
      associated with increased odds of poor social communication (alcohol: OR 1.46,
      95% CI 0.99-2.14; tobacco: OR 1.95, 95% CI 1.33-2.86) and poor social reciprocity
      (alcohol: OR 1.57, 95% CI 1.18-2.09; tobacco: OR 1.92, 95% CI 1.43-2.58;
      cannabis: OR 1.54, 95% CI 1.16-2.05). Overall, the relationship between social
      cognition and substance use was different in each temporal direction. Poor non
      verbal communication in childhood appeared protective against later substance
      use, while adolescent substance use was associated with decreased social
      cognitive performance.

PMID- 29058119
TI  - Comprehensive molecular characterisation of epilepsy-associated glioneuronal
      tumours.
AB  - Glioneuronal tumours are an important cause of treatment-resistant epilepsy.
      Subtypes of tumour are often poorly discriminated by histological features and
      may be difficult to diagnose due to a lack of robust diagnostic tools. This is
      illustrated by marked variability in the reported frequencies across different
      epilepsy surgical series. To address this, we used DNA methylation arrays and RNA
      sequencing to assay the methylation and expression profiles within a large cohort
      of glioneuronal tumours. By adopting a class discovery approach, we were able to
      identify two distinct groups of glioneuronal tumour, which only partially
      corresponded to the existing histological classification. Furthermore, by
      additional molecular analyses, we were able to identify pathogenic mutations in
      BRAF and FGFR1, specific to each group, in a high proportion of cases. Finally,
      by interrogating our expression data, we were able to show that each molecular
      group possessed expression phenotypes suggesting different cellular
      differentiation: astrocytic in one group and oligodendroglial in the second.
      Informed by this, we were able to identify CCND1, CSPG4, and PDGFRA as
      immunohistochemical targets which could distinguish between molecular groups. Our
      data suggest that the current histological classification of glioneuronal tumours
      does not adequately represent their underlying biology. Instead, we show that
      there are two molecular groups within glioneuronal tumours. The first of these
      displays astrocytic differentiation and is driven by BRAF mutations, while the
      second displays oligodendroglial differentiation and is driven by FGFR1
      mutations.

PMID- 29058120
TI  - Phenotyping cognitive impairment in dialysis patients: insights from experimental
      mouse models.

PMID- 29058122
TI  - Correction to: Psychosocial and Clinical Correlates of Fatigue in Haemodialysis
      Patients: the Importance of Patients' Illness Cognitions and Behaviours.
AB  - We wish to highlight a discrepancy with regards to the reported mean fatigue
      severity score (mean = 28.3, standard deviation = 6.5). Since publication we have
      followed this sample up over time and are currently evaluating the longitudinal
      trajectories of fatigue severity.

PMID- 29058123
TI  - Phosphorus availability in the source population influences response to dietary
      phosphorus quantity in a New Zealand freshwater snail.
AB  - We investigated whether previously documented variation among populations in
      availability of dietary phosphorus (P) is linked to heterogeneity in growth rate
      of the New Zealand freshwater snail Potamopyrgus antipodarum on a P-limited diet.
      We chose this system because P. antipodarum inhabits water bodies that vary in P
      availability and because P. antipodarum growth rate varies considerably in
      response to low P. We quantified specific growth rate and alkaline phosphatase
      (AP) expression in a diverse array of juvenile P. antipodarum fed high vs. low-P
      diets. We found strong associations between P content of epilithon in the source
      lake and P. antipodarum growth rate on high vs. low-P diets, with snails
      collected from lakes with relatively low-P epilithon showing the greatest
      increase in growth rate on the high-P relative to low-P diet. We also found
      substantial intraspecific variation in growth response to P limitation.
      Expression of AP also varied among lineages and was negatively associated with C:
      P of lake epilithon but did not explain the relationship between C: P in the lake
      of origin and sensitivity to P limitation. Together, our results demonstrate a
      strong signature of the P environment in the lake of origin on how this snail
      responds to P limitation as well as preliminary evidence for intraspecific
      variation of AP expression in animals.

PMID- 29058121
TI  - Multiple system atrophy: experimental models and reality.
AB  - Multiple system atrophy (MSA) is a rapidly progressing fatal synucleinopathy of
      the aging population characterized by parkinsonism, dysautonomia, and in some
      cases ataxia. Unlike other synucleinopathies, in this disorder the synaptic
      protein, alpha-synuclein (alpha-syn), predominantly accumulates in
      oligodendroglial cells (and to some extent in neurons), leading to maturation
      defects of oligodendrocytes, demyelination, and neurodegeneration. The mechanisms
      through which alpha-syn deposits occur in oligodendrocytes and neurons in MSA are
      not completely clear. While some studies suggest that alpha-syn might transfer
      from neurons to glial cells, others propose that alpha-syn might be aberrantly
      overexpressed by oligodendroglial cells. A number of in vivo models have been
      developed, including transgenic mice overexpressing alpha-syn under
      oligodendroglial promoters (e.g.: MBP, PLP, and CNP). Other models have been
      recently developed either by injecting synthetic alpha-syn fibrils or brain
      homogenates from patients with MSA into wild-type mice or by using viral vectors
      expressing alpha-syn under the MBP promoter in rats and non-human primates. Each
      of these models reproduces some of the neuropathological and functional aspects
      of MSA; however, none of them fully replicate the spectrum of MSA. Understanding
      better the mechanisms of how alpha-syn accumulates in oligodendrocytes and
      neurons will help in developing better models that recapitulate various
      pathogenic aspects of MSA in combination with translatable biomarkers of early
      stages of the disease that are necessary to devise disease-modifying therapeutics
      for MSA.

PMID- 29058124
TI  - Temporal changes in bird functional diversity across the United States.
AB  - Global changes are modifying the structure of species assemblages, but the
      generality of resulting diversity patterns and of their drivers is poorly
      understood. Any such changes can be detected and explained by comparing temporal
      trends in taxonomic and functional diversity over broad spatial extents. In this
      study, we addressed three complementary questions: How did bird taxonomic and
      functional diversity change over the past 40 years in the conterminous United
      States? Are these trends non-linear? Can temporal variations in functional
      diversity be explained by broad-scale changes in climate and vegetation
      productivity? We quantified changes in taxonomic and functional diversity for 807
      bird assemblages over the past four decades (1970-2011) considering a suite of 16
      ecological traits for 435 species. We found increases in local bird species
      richness and taxonomic equitability that plateaued in the early 2000's while
      total abundance declined over the whole period. Functional richness, the total
      range of traits in an assemblage, increased due to the rising prevalence of
      species with atypical life-history strategies and under-represented habitat or
      trophic preferences. However, these species did not trigger major changes in the
      functional composition of bird assemblages. Inter-annual variations in climate
      and primary productivity explained the richness of bird life-history traits in
      local assemblages, suggesting that these traits are influenced by broad-scale
      environmental factors, while others respond more to more local drivers. Our
      results highlight that a comparative analysis of the multiple facets of
      functional diversity can raise novel insights on processes underlying temporal
      trends in biodiversity.

PMID- 29058125
TI  - Imported malaria in pregnant women: report from a French University Centre.
AB  - OBJECTIVE: To describe malaria during pregnancy outside endemic areas. MATERIALS
      AND METHODS: We retrospectively reviewed all cases of imported malaria during
      pregnancy, diagnosed over a 11-year period in a French hospital. RESULTS AND
      CONCLUSION: We recovered 18 cases, all from sub-Saharan countries. The infection
      could appear distantly from arrival in France (up to 36 months), was asymptomatic
      in 3 cases, with anemia being the most common marker of infection (n = 14). The
      adverse consequences for the fetus (n = 3) or the newborn (n = 4) were frequent.
      Physicians should be aware of these atypical presentations in order to anticipate
      the diagnosis and improve the maternal and fetal prognosis.

PMID- 29058126
TI  - Time-Kill Analysis of Ceftolozane/Tazobactam Efficacy Against Mucoid Pseudomonas
      aeruginosa Strains from Cystic Fibrosis Patients.
AB  - INTRODUCTION: Mucoid Pseudomonas aeruginosa (MP) strains in cystic fibrosis (CF)
      patients are thought to initiate the chronic infection stage of CF and are
      associated with pulmonary function decline. OBJECTIVES: The purpose of this study
      was to assess the susceptibility of MP strains to ceftolozane/tazobactam and the
      efficacy of ceftolozane/tazobactam against MP strains compared with those for
      standard-of-care antipseudomonal antibiotics. METHODS: Ten clinical isolates of
      MP from CF patients were tested for susceptibility with Etest and time-kill
      analysis with ceftolozane/tazobactam compared with ceftazidime, cefepime,
      ciprofloxacin, meropenem, tobramycin, and polymyxin B. The physiologic free peak
      concentrations were used in the time-kill experiments. RESULTS:
      Ceftolozane/tazobactam minimum inhibitory concentrations ranged from 0.032 to 1.5
      mg/L. In the time-kill analysis, the mean starting inoculum for the isolates was
      6.29 +/- 0.22 log10 colony forming units (CFU) per milliliter. On average,
      ceftolozane/tazobactam, cefepime, ciprofloxacin, meropenem, tobramycin, and
      polymyxin B all demonstrated bactericidal activity. With all isolates taken into
      account, polymyxin B, tobramycin, meropenem, and ceftolozane/tazobactam 3 g were
      the most potent, with reductions in inoculum of 5.07 +/- 0.45, 4.58 +/- 2.2, 4.76
      +/- 0.71, and 4.17 +/- 0.94 log10 CFU/mL, respectively. Ceftolozane/tazobactam
      1.5 g, cefepime, and ciprofloxacin reduced the starting inoculum by 3.74 +/-
      0.99, 3.42 +/- 1.4, and 3.23 +/- 2.0 log10 CFU/mL, respectively. Despite 90%
      susceptibility, ceftazidime was bactericidal against seven of ten strains, with
      an average reduction in starting inoculum of 2.91 +/- 2.2 log10 CFU/mL.
      CONCLUSION: Ceftolozane/tazobactam activity against MP strains derived from CF
      patients was comparable to that of standard-of-care agents at both the 1.5-g dose
      and the 3-g dose. Further in vitro modeling and clinical trials are warranted.

PMID- 29058127
TI  - The effect of physical activity on fatigue among survivors of colorectal cancer:
      a systematic review and meta-analysis.
AB  - PURPOSE: Favorable health outcomes among cancer survivors are increasingly being
      attributed to lifestyle factors like physical activity, which is now promoted in
      clinical guidelines. However, the available evidence indicates that physical
      activity may also reduce fatigue in this patient group. In this systematic
      review, we aimed to examine whether physical activity could reduce fatigue among
      survivors of colorectal cancer. METHODS: The databases of Medline, CINAHL, and
      PsycINFO were systematically searched, using combinations of MeSH and free-text
      terms for colorectal cancer, physical activity, and fatigue. Randomized
      controlled trials and cohort studies with longitudinal data collection were
      included. We performed a random-effect meta-analysis. RESULTS: Seven studies were
      included, five were randomized controlled trials, and two were cohort studies. A
      meta-analysis of the randomized controlled trials, which comprised 630 survivors
      in total, failed to show that physical activity had a significant effect on
      fatigue (standardized mean difference = 0.21 (- 0.07 to 0.49)); however, reduced
      levels of fatigue were observed in all studies. The results for the cohort
      studies were inconclusive: one showed that increasing levels of physical activity
      were significantly associated with decreasing levels of fatigue; the other showed
      that decreasing levels of fatigue were not associated with increasing levels of
      physical activity. CONCLUSIONS: Based on the data reviewed, we cannot draw
      definitive conclusions about the effects of physical activity on fatigue. None of
      the included studies were performed among fatigued survivors of colorectal
      cancer. More research is needed in this population, ensuring that the trials are
      appropriately powered to find differences in fatigue.

PMID- 29058129
TI  - Does grip strength decrease in the very early stages of hematological treatment?
AB  - Muscle weakness in hematological cancer patients undergoing acute stages of
      treatment is an important concern and strong predictor of poor outcomes. However,
      evidence of strength loss in the very early stages of cancer treatment is not
      addressed. Here, we found that grip strength was compromised within the first 7
      days of hematological treatment (- 2.3 kg, P = 0.002). These findings are novel
      in elucidating lower handgrip strength in the first week of hematological
      treatment and encourage additional research focusing on handgrip strength in
      oncology patients under initial high-dose chemotherapy routine.

PMID- 29058128
TI  - Measurements and status of sleep quality in patients with cancers.
AB  - Sleep disturbance is identified as a prominent concern in cancer patients with
      detrimental effect on health outcome, which accompanies a decline in functional
      status, reduces quality of life, and even accelerates deterioration of disease.
      Therefore, in order to design safe and effective therapy, and improve the quality
      of life in cancer patients, it is necessary to seek the optimal measures of sleep
      quality evaluation, which include the objective assessments (e.g.,
      polysomnography [PSG], the bispectral index [BIS], actigraphy) and subjective
      assessments (e.g., Pittsburgh Sleep Quality Index [PSQI], Insomnia Severity Index
      [ISI], Epworth Sleepiness Scale [ESS], Consensus Sleep Diary [CSD]) and
      understand the status of sleep quality in cancer patients, especially patients
      with cancers in the breast, lung, head and neck, ovaries, and uterus. This review
      summarizes the common methods used to measure sleep quality and compares the
      sensitivity, specificity, and practicability of these methods. In addition, the
      status of sleep disturbance in patients with cancer is analyzed.

PMID- 29058130
TI  - The distress thermometer in survivors of gynaecological cancer: accuracy in
      screening and association with the need for person-centred support.
AB  - PURPOSE: Unrecognised psychological distress among cancer survivors may be
      identified using short screening tools. We validated the accuracy of the distress
      thermometer (DT) to detect psychological distress on the Hospital Anxiety and
      Depression Scale (HADS) among early stage gynaecological cancer survivors and
      whether the women's DT and HADS scores were associated with the need of an
      individualised supportive intervention. METHODS: One hundred sixty-five
      gynaecological cancer survivors answered DT and HADS before randomisation in a
      trial testing a nurse-led, person-centred intervention using supportive
      conversations. The number of conversations was decided in the woman-nurse dyad
      based on the woman's perceived need. Nurses were unaware of the women's DT and
      HADS scores. We validated DT's accuracy for screening using HADS as gold standard
      and receiver operating characteristic curves. Associations between DT and HADS
      scores and the number of conversations received were investigated. RESULTS: For
      screening of distress (HADS >= 15), a DT score >= 2, had a sensitivity of 93%
      (95% CI 82-98%), a specificity of 40% (32-49%), and positive and negative
      predictive values of 36% (28-45%), and 94% (84-98%), respectively; area under
      curve was 0.73 (0.64-0.81). Higher DT and HADS scores were associated with more
      interventional conversations. CONCLUSIONS: In gynaecological cancer survivors, DT
      may perform fairly well as a first stage screening tool for distress, but a
      second stage is likely needed due to a high number of false positives. DT and
      HADS scores may predict the number of supportive conversations needed in an
      individualised intervention in gynaecological cancer survivors.

PMID- 29058131
TI  - Insulin and Its Cardiovascular Effects: What Is the Current Evidence?
AB  - PURPOSE OF REVIEW: In this article, we examine the nature of the complex
      relationship between insulin and cardiovascular disease. With metabolic
      abnormalities comes increased risk for cardiovascular complications. We discuss
      the key factors implicated in development and progression of cardiovascular
      disease, its relationship to insulin therapy, and what can be learned from large,
      recent cardiovascular outcome studies. RECENT FINDINGS: Preclinical studies
      suggest that insulin has positive effects of facilitating glucose entry into
      cells and maintaining euglycemia and negative effects of favoring obesity and
      atherogenesis under certain conditions. Confounding this relationship is that
      cardiovascular morbidity is linked closely to duration and control of diabetes,
      and insulin is often used in patients with diabetes of longer duration. However,
      more recent clinical studies examining the cardiovascular safety of insulin
      therapy have been reassuring. Diabetes and cardiovascular outcomes are closely
      linked. Many studies have implicated insulin resistance and hyperinsulinemia as a
      major factor for poor cardiovascular outcomes. Additional studies link the
      anabolic effects of therapeutic insulin to weight gain, along with hypoglycemia,
      which may further aggravate cardiovascular risk in this population. Though good
      glycemic control has been shown to improve microvascular risks in type 1 and type
      2 diabetes, what are the known cardiovascular effects of insulin therapy? The
      ORIGIN trial suggests at least a neutral effect of the basal insulin glargine on
      cardiovascular outcomes. Recent studies have demonstrated that ultra-long-acting
      insulin analogs like insulin degludec are non-inferior to insulin glargine with
      regard to cardiovascular outcomes.

PMID- 29058133
TI  - 12. Deutscher Wirbelsaulenkongress Jahrestagung der Deutschen
      Wirbelsaulengesellschaft 30. November - 2. Dezember 2017, Stuttgart.

PMID- 29058132
TI  - An evaluation of abdominal wall closure in general surgical and gynecological
      residents.
AB  - PURPOSE: To evaluate abdominal wall closure knowledge base and technical skills
      in surgical and OB/GYN residents. METHODS: Residents consented to participate in
      a skills laboratory and quiz. The skills portion involved closure of a 10-cm
      incision on a simulated abdominal wall. Participants were timed, filmed, and
      graded using a standardized grading system. RESULTS: Thirty surgical and OB/GYN
      residents participated. All residents reported closing the abdominal wall
      continuously, 97% preferred slowly absorbing sutures (28/29), 97% preferred
      taking 1-cm bites (29/30), and 93% spaced bites 1 cm apart (27/29). However, 77%
      (10/13) of surgery residents identified 4:1 as the ideal suture to wound length
      ratio; 47% (7/15) of OB/GYN residents believed it to be 2:1, and another 40%
      (6/15) indicated 3:1 (p < 0.0001). In the simulation, OB/GYN residents used
      significantly fewer stitches (p = 0.0028), significantly more distance between
      bites (p < 0.0001), and significantly larger bite size (p < 0.0001) than surgery
      residents. When graded, there was no significant difference between programs.
      CONCLUSIONS: Despite some knowledge regarding the principles of abdominal wall
      closure among surgical and OB/GYN residents, more instruction is needed. We
      identified some differences in knowledge base and techniques for abdominal wall
      closure among general surgery and OB/GYN residents, which are likely due to
      differences in educational curriculums.

PMID- 29058134
TI  - Distraction arthrodesis of the sacroiliac joint: 2-year results of a descriptive
      prospective multi-center cohort study in 171 patients.
AB  - PURPOSE: The aim of the given study was to evaluate the long-term outcomes of
      patients undergoing sacroiliac joint (SIJ) distraction arthrodesis to treat SIJ
      related pain. METHODS: Descriptive prospective multi-center cohort study
      involving 20 hospitals in Germany. Between January 2011 and June 2012, 171
      patients with chronic SIJ pain underwent indirect arthrodesis of the SIJ using a
      distraction implant. The patients were questioned prior to surgery, 6-weeks, and
      3-, 6-, 12- and 24-months postoperatively. Overall patient satisfaction was
      surveyed along with pain medication intake, the Million Visual Analogue Scale
      (MVAS), Oswestry Disability Index (ODI), Short-form McGill Pain Questionnaire (SF
      MPQ), 12-Item Short-Form Health Survey (SF-12), Visual Analogue Scale (VAS) and a
      pain drawing. Bony fusion of the SIJ was evaluated using X-ray and computed
      tomography (CT). RESULTS: A majority of patients (73%) reported to feel better or
      much better 24 months post-surgery, 49% of the patients reduced their pain
      medication intake. The MVAS dropped from 63 to 36%, the ODI improved from 51 to
      33%, the SF-MPQ decreased from 50 to 31%, the SF-12 physical component summary
      rose from 22 to 41%, the mental component summary increased from 40 to 55%, and
      pain as measured by the VAS decreased from 74 to 37 points (all comparisons p <
      0.001). In the follow-up CT scans 31% of the patients showed SIJ fusion.
      CONCLUSIONS: SIJ distraction arthrodesis has shown satisfactory outcomes in
      patients with SIJ-related pain for all scores reported in the surveys,
      accompanied by increased functionality.

PMID- 29058135
TI  - The value of patient global assessment in lumbar spine surgery: an evaluation
      based on more than 90,000 patients.
AB  - PURPOSE: There are two, principally different ways to obtain patient opinions
      regarding the outcome of spine surgery: using prospective multi-item
      questionnaires preoperatively and at follow-up, and using a retrospective single
      item question at follow-up-both methods have distinct advantages and limitations.
      The purpose of the study was to explore the utility of using the simple
      transition question global assessment, GA, ("How is your back/leg pain today as
      compared to before the surgery?") as an overall patient-reported outcome measure
      (PROM) based on the large real-life database in the Swedish spine registry
      (Swespine). METHODS: The correlation between GA and the score-changes and the
      final scores at 1 year of follow-up for the PROMs VAS, ODI, and EQ-5D was
      examined. The correlations between GA and item-specific domains within the ODI,
      EQ-5D and SF-36 as well as the discriminative ability of PROMs with GA as
      reference criterion were also analysed. The cohort consisted of 94,132 patients
      registered in Swespine who were surgically treated for disc herniation, spinal
      stenosis or degenerative disc disease. RESULTS: The correlation coefficients for
      GA vs. the score-changes were lower than for GA vs final scores. For VAS they
      ranged for the different diagnosis groups from 0.33 to 0.61 and from 0.50 to
      0.79, respectively. For ODI, the corresponding values ranged from 0.43 to 0.65
      and 0.63 to 0.76; for the EQ-5D from 0.32 to 0.45 and 0.54 to 0.71. Further, GA
      showed a somewhat stronger correlation to pain-specific PROMs than to quality-of
      life PROMs. CONCLUSIONS: The single-item outcome measure global assessment (GA)
      appears to be a feasible overall patient-reported outcome measure (PROM) and a
      useful reference for interpreting the scores of patient-reported outcome
      measures.

PMID- 29058136
TI  - Answer to the Letter to the Editor of Wang Kai et al. concerning "Radiographic
      evaluation of indirect decompression of mini-open anterior retroperitoneal lumbar
      interbody fusion: oblique lateral interbody fusion for degenerated lumbar
      spondylolisthesis" by Jun Sato et al. Eur Spine J (2017) 26:671-678.

PMID- 29058137
TI  - Zonal differences in risk and pattern of pedicle screw perforations in adolescent
      idiopathic scoliosis (AIS): a computerized tomography (CT) review of 1986 screws.
AB  - PURPOSE: To evaluate the zonal differences in risk and pattern of pedicle screw
      perforations in adolescent idiopathic scoliosis (AIS) patients. METHODS: The
      scoliosis curves were divided into eight zones. CT scans were used to assess
      perforations: Grade 0, Grade 1(< 2 mm), Grade 2(2-4 mm) and Grade 3(> 4 mm).
      Anterior perforations were classified into Grade 0, Grade 1(< 4 mm), Grade 2(4-6
      mm) and Grade 3(> 6 mm). Grade 2 and 3 (except lateral grade 2 and 3 perforation
      over thoracic vertebrae) were considered as 'critical perforations'. RESULTS:
      1986 screws in 137 patients were analyzed. The overall perforation rate was 8.4%
      after exclusion of the lateral perforation. The highest medial perforation rate
      was at the transitional proximal thoracic (PT)/main thoracic (MT) zone (6.9%),
      followed by concave lumbar (6.7%) and convex main thoracic (MT) zone (6.1%). The
      overall critical medial perforation rate was 0.9%. 33.3% occurred at convex MT
      and 22.2% occurred at transitional PT/MT zone. There were 39 anterior
      perforations (overall perforation rate of 2.0%). 43.6% occurred at transitional
      PT/MT zone, whereas 23.1% occurred at concave PT zone. The overall critical
      anterior perforation rate was 0.6%. 5/12 (41.7%) critical perforations occurred
      at concave PT zone, whereas four perforations occurred at the transitional PT/MT
      zone. There were only two symptomatic left medial grade 2 perforations (0.1%)
      resulting radiculopathy, occurring at the transitional main thoracic (MT)/Lumbar
      (L) zone. CONCLUSION: Overall pedicle perforation rate was 8.4%. Highest rate of
      critical medial perforation was at the convex MT zone and the transitional PT/MT
      zone, whereas highest rate of critical anterior perforation was at the concave PT
      zone and the transitional PT/MT zone. The rate of symptomatic perforations was
      0.1%.

PMID- 29058139
TI  - Consortia formed by yeasts and acetic acid bacteria Asaia spp. in soft drinks.
AB  - Yeast strains and acetic acid bacteria were isolated from spoiled soft drinks
      with characteristic flocs as a visual defect. Polymerase chain reaction and
      amplification of a partial region of the LSU rRNA gene identified the bacteria as
      Asaia spp. Sequence analysis of the D1/D2 region of the 26S rDNA in turn
      identified the yeast isolates as Wickerhamomyces anomalus, Dekkera bruxellensis
      and Rhodotorula mucilaginosa. The hydrophobicity and adhesion properties of the
      yeasts were evaluated in various culture media, taking into account the
      availability of nutrients and the carbon sources. The highest hydrophobicity and
      best adhesion properties were exhibited by the R. mucilaginosa cells. Our results
      suggest that Asaia spp. bacterial cells were responsible for the formation of
      flocs, while the presence of yeast cells may help to strengthen the structure of
      co-aggregates.

PMID- 29058140
TI  - Diversity and dynamics of lactic acid bacteria in Atole agrio, a traditional
      maize-based fermented beverage from South-Eastern Mexico, analysed by high
      throughput sequencing and culturing.
AB  - The purpose of this work was to analyse the diversity and dynamics of lactic acid
      bacteria (LAB) throughout the fermentation process in Atole agrio, a traditional
      maize based food of Mexican origin. Samples of different fermentation times were
      analysed using culture-dependent and -independent approaches. Identification of
      LAB isolates revealed the presence of members of the genera Pediococcus,
      Weissella, Lactobacillus, Leuconostoc and Lactococcus, and the predominance of
      Pediococcus pentosaceus and Weissella confusa in liquid and solid batches,
      respectively. High-throughput sequencing (HTS) of the 16S rRNA gene confirmed the
      predominance of Lactobacillaceae and Leuconostocaceae at the beginning of the
      process. In liquid fermentation Acetobacteraceae dominate after 4 h as pH
      decreased. In contrast, Leuconostocaceae dominated the solid fermentation except
      at 12 h that were overgrown by Acetobacteraceae. Regarding LAB genera,
      Lactobacillus dominated the liquid fermentation except at 12 h when Weissella,
      Lactococcus and Streptococcus were the most abundant. In solid fermentation
      Weissella predominated all through the process. HTS determined that Lactobacillus
      plantarum and W. confusa dominated in the liquid and solid batches, respectively.
      Two oligotypes have been identified for L. plantarum and W. confusa populations,
      differing in a single nucleotide position each. Only one of the oligotypes was
      detected among the isolates obtained from each species, the biological
      significance of which remains unclear.

PMID- 29058138
TI  - The Paradigms They Are a-Changin': past, present and future of PVC bacteria
      research.
AB  - These are exciting times for PVC researchers! The PVC superphylum is composed of
      the bacterial phyla Planctomycetes, Verrucomicrobia, Chlamydiae (those three
      founders giving it its name), Lentisphaerae and Kirimatiellaeota as well as some
      uncultured candidate phyla, such as the Candidatus Omnitrophica (previously known
      as OP3). Despite early debates, most of the disagreements that surround this
      group of bacteria have been recently resolved. In this article, we review the
      history of the study of PVC bacteria, with a particular focus on the
      misinterpretations that emerged early in the field and their resolution. We begin
      with a historical perspective that describes the relevant facts of PVC research
      from the early times when they were not yet termed PVC. Those were controversial
      times and we refer to them as the "discovery age" of the field. We continue by
      describing new discoveries due to novel techniques and data that combined with
      the reinterpretations of old ones have contributed to solve most of the
      discordances and we refer to these times as the "illumination age" of PVC
      research. We follow by arguing that we are just entering the "golden age" of PVC
      research and that the future of this growing community is looking bright. We
      finish by suggesting a few of the directions that PVC researches might take in
      the future.

PMID- 29058141
TI  - The Impact of Sentinel Node-Mapping in Staging High-Risk Endometrial Cancer.
AB  - BACKGROUND: This study aimed to determine the impact of sentinel lymph node (SLN)
      mapping on the staging of high-risk endometrial cancer (endometrioid grade 3,
      serous, clear cell, carcinosarcoma, deep myometrial invasion, or angiolymphatic
      invasion). METHODS: The study analyzed a series of 236 patients treated at AC
      Camargo Cancer Center from June 2007 to February 2017. The compared 75 patients
      who underwent SLN-mapping (SLN group) with 161 patients who received pelvic +/-
      para-aortic lymphadenectomy (N-SLN group). Patients with adnexal, peritoneal, or
      suspicious node metastases were excluded from the study. RESULTS: The groups did
      not differ in terms of age, histologic type, or presence of deep myometrial
      invasion. The overall detection rate for SLNs was 85.3%, and bilateral SLNs were
      observed in 60% of the patients. Of 20 positive SLNs, 8 (40%) were detected only
      after immunohistochemistry (IHC). The findings showed an overall sensitivity of
      90%, a negative predictive value of 95.7%, and a false-negative predictive value
      of 4.3%. The SLN group had more pelvic node metastases detected than the N-SLN
      group (26.7 vs 14.3%; p = 0.02). However, the rate of para-aortic node metastases
      did not differ between the two groups (13.5 vs 5.6%; p = 0.12). Five patients
      (3.5%) in the N-SLN group had isolated para-aortic node metastases versus none in
      the patients with SLN mapped. Additionally, the SLN group received more adjuvant
      chemotherapy (48 vs 33.5%; p = 0.03). CONCLUSIONS: The data suggest that SLN
      mapping identifies more pelvic node metastases than lymph node dissection alone
      and increases the node detection rate by 12.5% after IHC. Furthermore, no
      isolated para-aortic node metastases are observed when SLN is detected.

PMID- 29058142
TI  - Similar Significance of Lymphovascular Invasion with Different Treatment
      Modalities Among Esophageal Squamous Cell Carcinoma.

PMID- 29058143
TI  - Performance Analysis of the American Joint Committee on Cancer 8th Edition
      Staging System for Retroperitoneal Sarcoma and Development of a New Staging
      Algorithm for Sarcoma-Specific Survival.
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) recently published the
      8th edition of the AJCC Cancer Staging Manual. Major changes were made to the
      staging algorithm for retroperitoneal sarcoma; however, whether these changes
      improve staging system performance is questionable. METHODS: This retrospective
      cohort analysis of 3703 adult patients with retroperitoneal sarcoma in the
      Surveillance, Epidemiology, and End Results (SEER) database compares a novel
      staging system incorporating histologic subtype of sarcoma with current and prior
      AJCC soft tissue sarcoma staging systems using multiple statistical techniques.
      The effect of tumor size on sarcoma-specific survival was also assessed by
      flexible, non-linear Cox proportional hazard regression using restricted cubic
      splines and fractional polynomials. RESULTS: The relationship between the
      covariate-adjusted log hazard for disease-specific survival and tumor size is non
      linear. Although the new AJCC T classification approximates this hazard fairly
      well, the overall prognostic impact of tumor size is limited after accounting for
      other predictive factors. Predictive accuracy and concordance indices of the AJCC
      8th edition staging system for retroperitoneal sarcoma are significantly lower
      than the prior 7th edition. A proposed staging system incorporating histologic
      grade, tumor size, and histologic subtype is superior to both the AJCC 7th and
      8th editions in predicting sarcoma-specific survival. CONCLUSION: AJCC committees
      should not revise tumor staging algorithms unless the changes actually improve
      the staging system. A proposed staging scheme incorporating data regarding
      histologic subtype of sarcoma performs significantly better than both the 7th and
      8th AJCC staging systems.

PMID- 29058144
TI  - Rectal Gastrointestinal Stromal Tumor (GIST) in the Era of Imatinib: Organ
      Preservation and Improved Oncologic Outcome.
AB  - BACKGROUND: Approximately 5% of gastrointestinal stromal tumors (GISTs) originate
      in the rectum, and historically, radical resection was commonly performed. Little
      is known about the outcome for rectal GIST in the era of imatinib. METHODS: Using
      a prospectively maintained database, this study retrospectively analyzed 47
      localized primary rectal GISTs treated at our center from 1982 to 2016,
      stratified by when imatinib became available in 2000. Overall survival (OS),
      disease-specific survival (DSS), and recurrence-free survival (RFS) were analyzed
      by the Kaplan-Meier method. RESULTS: Rectal GISTs represented 7.1% of 663 primary
      GISTs. The findings showed 17 patients in the pre-imatinib era and 30 patients in
      the imatinib era. The two groups had similar follow-up evaluation, age, gender,
      Miettinen risk, and distance to the anal verge. In the imatinib era, tumors were
      smaller at diagnosis (median 4 vs. 5 cm; p = 0.029), and 24 of the 30 patients
      received perioperative imatinib. In the high-risk patients, organ preservation
      and negative margins were more common among the 13 patients treated with
      neoadjuvant imatinib than among the 21 patients treated directly with surgery.
      High-risk patients who received perioperative imatinib (n = 15) had greater (or
      nearly significantly greater) 5-year OS, DSS, local RFS, and distant RFS than
      those who did not (n = 19) (91, 100, 100, and 71% vs. 47, 65, 74, and 41%; p =
      0.049, 0.052, 0.077, 0.051, respectively). In the imatinib era, no patient has
      had a local recurrence or death due to GIST. CONCLUSIONS: The use of imatinib is
      associated with organ preservation and improved oncologic outcome for patients
      with rectal GIST.

PMID- 29058145
TI  - Vitamin Status and the Development of Postoperative Cognitive Decline in Elderly
      Surgical Oncologic Patients.
AB  - BACKGROUND: This study aimed to evaluate the influence that serum levels of
      vitamin B12, folate, and homocysteine have on the development of short-term
      postoperative cognitive decline in the elderly surgical oncology patient.
      METHODS: This study was part of a prospective cohort study focused on
      postoperative cognitive outcomes for patients 65 years of age or older undergoing
      surgery for a solid malignancy. Postoperative cognitive decline was defined as
      the change in the combined results of the Ruff Figural Fluency Test and the Trail
      Making Test Parts A and B. Patients with the highest change in scores 2 weeks
      postoperatively compared with baseline were considered to be patients with
      cognitive decline. Patients with the lowest change were considered to be patients
      without cognitive decline. To analyze the effect of vitamin levels on the changes
      in postoperative cognitive scores, uni- and multivariate logistic regression
      analysis were performed. RESULTS: The study enrolled 61 patients with and 59
      patients without postoperative cognitive decline. Hyperhomocysteinemia was
      present in 14.2% of the patients. Patients with postoperative cognitive decline
      more often had hyperhomocysteinemia (27.9 vs 10.2%). Hyperhomocysteinemia was
      associated with a higher chance for the development of postoperative cognitive
      decline (odds ratioadjusted, 11.9; 95% confidence interval, 2.4-59.4).
      Preoperative vitamin B12 or folate deficiency were not associated with the
      development of postoperative cognitive decline. CONCLUSION: Preoperative
      hyperhomocysteinemia is associated with the development of postoperative
      cognitive decline. The presence of preoperative hyperhomocysteinemia could be an
      indicator for an increased risk of postoperative cognitive decline developing in
      the elderly.

PMID- 29058147
TI  - Regulation of the chikungunya-virus-induced innate inflammatory response by
      protein tyrosine phosphatase non-receptor 6 in muscle cells.
AB  - Chikungunya virus (CHIKV)-induced myositis is an emerging affliction with high
      incidence globally. Given the essential regulatory role of protein tyrosine
      phosphatase non-receptor 6 (PTPN6) in virus-induced myositis, the expression of
      the PTPN6 and TNF-alpha genes in a CHIKV-infected muscle cell line was examined
      by quantitative PCR, and the expression of PTPN6 and STAT 3 was examined by
      immunoblotting. In addition, the effect of PTPN6 siRNA treatment on TNF-alpha
      gene expression was assessed. Increased higher expression of PTPN6 and TNF-alpha,
      and significant upregulation of TNF-alpha upon PTPN6 siRNA treatment were
      observed, suggesting that CHIKV has the ability to induce host PTPN6 gene
      expression, which may lead to a decreased pro-inflammatory immune response in the
      host.

PMID- 29058148
TI  - Complete genome sequence of two tomato-infecting begomoviruses in Venezuela:
      evidence of a putative novel species and a novel recombinant strain.
AB  - At least six begomovirus species have been reported infecting tomato in
      Venezuela. In this study the complete genomes of two tomato-infecting begomovirus
      isolates (referred to as Trujillo-427 and Zulia-1084) were cloned and sequenced.
      Both isolates showed the typical genome organization of New World bipartite
      begomoviruses, with DNA-A genomic components displaying 88.8% and 90.3%
      similarity with established begomoviruses, for isolates Trujillo-427 and Zulia
      1084, respectively. In accordance to the guidelines for begomovirus species
      demarcation, the Trujillo-427 isolate represents a putative new species and the
      name "Tomato wrinkled mosaic virus" is proposed. Meanwhile, Zulia-1084 represents
      a putative new strain classifiable within species Tomato chlorotic leaf
      distortion virus, for which a recombinant origin is suggested.

PMID- 29058146
TI  - Human nicotinic receptors in chromaffin cells: characterization and pharmacology.
AB  - During the last 10 years, we have been working on human chromaffin cells obtained
      from the adrenal gland of organ donors that suffered encephalic or cardiac death.
      We first electrophysiologically characterized the nicotinic acetylcholine
      receptors (nAChRs) activated by acetylcholine, and their contribution to the
      exocytosis of chromaffin vesicles and release of catecholamines. We have shown
      that these cells possess an adrenergic phenotype. This phenotype may contribute
      to an increased expression of alpha7 nAChRs in these cells, allowing for
      recording of alpha7 nAChR currents, something that had previously not been
      achieved in non-human species. The use of alpha-conotoxins allowed us to
      characterize non-alpha7 nAChR subtypes and, together with molecular biology
      experiments, conclude that the predominant nAChR subtype in human chromaffin
      cells is alpha3beta4* (asterisk indicates the posible presence of additional
      subunits). In addition, there is a minor population of alphaxbeta2 nAChRs. Both
      alpha7 and non-alpha7 nAChR subtypes contribute to the exocytotic process.
      Exocytosis mediated by nAChRs could be as large in magnitude as that elicited by
      calcium entry through voltage-dependent calcium channels. Finally, we have also
      investigated the effect of nAChR-targeted tobacco cessation drugs on
      catecholamine release in chromaffin cells. We have concluded that at therapeutic
      concentrations, varenicline alone does not increase the frequency of action
      potentials evoked by ACh. However, varenicline in the presence of nicotine does
      increase this frequency, and thus, in the presence of both drugs, the probability
      of increased catecholamine release in human chromaffin cells is high.

PMID- 29058149
TI  - Picornaviridae-the ever-growing virus family.
AB  - Picornaviruses are small, nonenveloped, icosahedral RNA viruses with positive
      strand polarity. Although the vast majority of picornavirus infections remain
      asymptomatic, many picornaviruses are important human and animal pathogens and
      cause diseases that affect the central nervous system, the respiratory and
      gastrointestinal tracts, heart, liver, pancreas, skin and eye. A stunning
      increase in the number of newly identified picornaviruses in the past decade has
      shown that picornaviruses are globally distributed and infect vertebrates of all
      classes. Moreover, picornaviruses exhibit a surprising diversity of both genome
      sequences and genome layouts, sometimes challenging the definition of taxonomic
      relevant criteria. At present, 35 genera comprising 80 species and more than 500
      types are acknowledged. Fifteen species within five new and three existing genera
      have been proposed in 2017, but more than 50 picornaviruses still remain
      unassigned.

PMID- 29058150
TI  - Next-generation sequencing of five new avian paramyxoviruses 8 isolates from
      Kazakhstan indicates a low genetic evolution rate over four decades.
AB  - Five avian paramyxoviruses of serotype 8 (APMV-8) were isolated during a study
      monitoring wild birds in Kazakhstan in 2013 and each was further characterized.
      The viruses were isolated from three White-fronted geese (Anser albifrons), one
      Whooper swan (Cygnus cygnus), and one Little stint (Calidris minuta). Before our
      study, only two complete APMV-8 sequences had been reported worldwide since their
      discovery in the USA and Japan in the 1970s. We report the complete genome
      sequences of the newly detected viruses and analyze the genetic evolution of the
      APMV-8 viruses over four decades.

PMID- 29058151
TI  - First detection of Nebovirus and Norovirus from cattle in China.
AB  - Neboviruses and genogroup III noroviruses (NoVsGIII) are causative agents of calf
      diarrhea. The purpose of this study was to investigate the presence of
      neboviruses and noroviruses in cattle in China. Twenty-eight diarrhea fecal
      samples collected from 5 different farms were analyzed by RT-PCR. The results
      showed that 3 nebovirus positive samples were detected on 2 farms, with two
      strains being related to Bo/DijonA216/06/FR strain and the other one clustering
      with NB-like strains. Meanwhile, 3 norovirus positive samples were detected on 3
      farms, all of which belonged to genotype 1. Our results confirmed the presence of
      neboviruses and NoVsGIII in China for the first time, and supported the presence
      of a novel "DijonA216-like" nebovirus genotype.

PMID- 29058152
TI  - Cystic renal mass in an infant with significant family history: Questions.

PMID- 29058153
TI  - Effects of growth hormone treatment on adult height in severely short children
      with X-linked hypophosphatemic rickets.
AB  - BACKGROUND: We recently showed that a 3-year growth hormone (GH) treatment
      improves linear growth in severely short children with X-linked hypophosphatemic
      rickets (XLH). It is unknown if GH therapy increases adult height in XLH
      patients. METHODS: We carried out a follow-up analysis of a randomized controlled
      open-label GH study in short prepubertal children with XLH on phosphate and
      active vitamin D treatment. The changes in SD scores (SDS) of height, sitting
      height, leg and arm length, and sitting height index (i.e., the ratio between
      sitting height and height) were analyzed in 11 out of 16 patients followed-up
      until adult height. RESULTS: At baseline, XLH patients showed disproportionately
      short stature with reduced standardized height (-3.2 +/- 0.6), sitting height (
      1.7 +/- 0.6), leg (-3.7 +/- 0.7) and arm (-2.5 +/- 0.8) length, and markedly
      elevated sitting height index (3.3 +/- 0.6; each p < 0.01 versus healthy
      children). In GH-treated patients, adult height, sitting height, leg length, and
      arm length exceeded baseline values by 0.7 SDS, 1.7 SDS, 0.7 SDS, and 1.2 SDS
      respectively, although this was only significant for sitting height. In controls,
      no significant changes in linear body dimensions were noted. Adult height did not
      statistically differ between groups (-2.4 +/- 0.7 vs -3.3 +/- 1.2, p = 0.082). GH
      did not exaggerate body disproportion. CONCLUSIONS: Growth hormone treatment did
      not significantly increase adult height in this group of short children with XLH,
      which may be at least partly due to the small number of patients included in our
      study.

PMID- 29058155
TI  - Preoperative levels of urinary uromodulin predict acute kidney injury after
      pediatric cardiopulmonary bypass surgery.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication of cardiopulmonary
      bypass surgery (CPB) in children. Several promising postoperative AKI biomarkers
      have been identified, but no preoperative biomarkers are available. We evaluated
      the association of urinary uromodulin (uUMOD) with postoperative AKI. METHODS:
      One hundred and one children undergoing CPB were enrolled. Urine was collected
      prior to CPB, and AKI was defined as ?50% increase in serum creatinine from
      preoperative baseline within 48 h of surgery. RESULTS: Forty-seven patients (47%)
      developed AKI, and 92% of participants in the lowest quartile of preoperative
      uUMOD concentrations developed AKI compared with 8% in the highest quartile.
      Patients with preoperative uUMOD levels in the lowest quartile had 132.3*
      increased risk of postoperative AKI versus the highest quartile. Raw uUMOD levels
      were significantly lower in patients with AKI vs. no AKI. Significance was
      unchanged after correcting uUMOD levels for urinary creatinine. Receiver
      operating characteristic analysis showed preoperative uUMOD strongly predicted
      postoperative AKI, with area under the curve (AUC) 0.90. Stepwise logistic
      regression analysis revealed a model combining uUMOD, and bypass time predicted
      AKI at p<0.001. Neither Risk Adjustment for Congenital Heart Surgery 1 (RACHS)
      score nor age improved the model's ability to predict AKI. Independent analysis
      demonstrated that while bypass time was associated with AKI, the predictive
      ability of bypass time (AUC 0.77) was less than that of preoperative uUMOD levels
      (AUC 0.9). CONCLUSIONS: Children with lowest preoperative levels of uUMOD have
      greatly increased risk of AKI post-CPB. If uUMOD were used to risk-stratify
      patients undergoing CPB, clinical measures could be taken to minimize AKI
      development.

PMID- 29058154
TI  - Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic
      syndrome.
AB  - BACKGROUND: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare
      condition. The disease pathophysiology remains elusive. However, bi-allelic
      mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1
      were linked to a high risk of developing the disease. METHODS: Clinical data were
      analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a
      potential autosomal recessive (AR) inheritance. Exome sequencing was performed in
      a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1
      were genotyped in the whole cohort. RESULTS: Transmission was compatible with an
      AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that
      familial SSNS is a monogenic trait. Clinical features did not differ between AR
      and AD groups. All patients, including primary (n = 7) and secondary steroid
      resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional
      immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly
      linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did
      not reveal any pathogenic mutation, neither did EMP2 sequencing. CONCLUSIONS:
      Taken together, these results highlight the clinical and genetic heterogeneity in
      familial SSNS. Clinical findings sustain an immune origin in all patients,
      whatever the initial steroid-sensitivity. The absence of a variant shared by two
      families and the HLA-DQA1 variation enrichments suggest a complex mode of
      inheritance.

PMID- 29058156
TI  - [Indications and contraindications for modern compression therapy].
AB  - Compression therapy is a physical therapy with few side effects, which is used
      especially in patients with edema of the lower extremities. The indication for
      compression therapy is given here for edema of very different origins such as,
      for example, venous or lymphatic disease symptoms as well as renal insufficiency,
      obesity or inflammation. However, different contraindications must be considered
      in these patients. Of particular importance are the advanced peripheral arterial
      occlusive disease and the polyneuropathy, which need special attention.Due to the
      large number of different compression materials and systems available today, in
      spite of these contraindications, compression therapy can be carried out with a
      large proportion of patients with edema of the lower extremities. The therapy
      should be adapted to the comorbidities and individual needs as well as personal
      abilities in the context of a patient-oriented care.

PMID- 29058157
TI  - Potential of asphericity as a novel diagnostic parameter in the evaluation of
      patients with 68Ga-PSMA-HBED-CC PET-positive prostate cancer lesions.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic value of the
      asphericity (ASP) as a novel quantitative parameter, reflecting the spatial
      heterogeneity of tracer uptake, in the staging process of patients with 68Ga-PSMA
      HBED-CC positron emission tomography (PET)-positive prostate cancer (PC). In this
      study, 37 patients (median age 72 years, range 52-82 years) with newly diagnosed
      PC, who received a 68Ga-PSMA-HBED-CC PET fused with computed tomography (68Ga
      PSMA-PET/CT), a magnetic resonance imaging (MRI) of the prostate, and a core
      needle biopsy (within 74.2 +/- 80.2 days) with an available Gleason score (GSc)
      were extracted from the local database. The ASP and the viable tumor volume (VTV)
      was calculated using the rover software (ABX GmbH, Radeberg, Germany), a
      segmentation tool for automated tumor volume delineation. Additionally,
      parameters including total lesion binding rate (TLB), maximum, mean and peak
      standardized uptake value (SUVmax/mean/peak), prostate-specific antigen (PSA),
      D'Amico classification, and prostate imaging reporting and data system (PI-RADS)
      were analyzed. RESULTS: The ASP mean differed significantly (p <= 0.05) between
      the different GSc groups: GSc 6-7: 11.9 +/- 4.8%, GSc 8: 25.5 +/- 4.8%, GSc 9-10:
      33.3 +/- 6.8%. A significant correlation between ASP and GSc (rho = 0.88; CI 0.78
      0.94; p < 0.05) was measured. The ASP enabled an independent (p > 0.05)
      prediction of the GSc. A moderate correlation was measured between ASP and the
      D'Amico classification (rho = 0.6; CI 0.32-0.78; p < 0.05). The VTV showed a
      moderate correlation with the SUVmax (rho = 0.58; CI 0.32-0.76; p < 0.05) and the
      GSc (rho = 0.51; CI 0.23-0.72; p < 0.05). CONCLUSION: The asphericity in 68Ga
      PSMA-PET could represent a promising novel quantitative parameter for an improved
      non-invasive tumor staging of patients with PC.

PMID- 29058159
TI  - Beliefs in and About God and Attitudes Toward Voluntary Euthanasia.
AB  - I use data from the General Social Survey to evaluate several hypotheses
      regarding how beliefs in and about God predict attitudes toward voluntary
      euthanasia. I find that certainty in the belief in God significantly predicts
      negative attitudes toward voluntary euthanasia. I also find that belief in a
      caring God and in a God that is the primary source of moral rules significantly
      predicts negative attitudes toward voluntary euthanasia. I also find that
      respondents' beliefs about the how close they are to God and how close they want
      to be with God predict negative attitudes toward voluntary euthanasia. These
      associations hold even after controlling for religious affiliation, religious
      attendance, views of the Bible, and sociodemographic factors. The findings
      indicate that to understand individuals' attitudes about voluntary euthanasia,
      one must pay attention to their beliefs in and about God.

PMID- 29058158
TI  - Religious Affiliation, Religiosity, and Spirituality in Pediatric Residents:
      Effects on Communication and Self-Efficacy with Adolescents in a Clinical
      Setting.
AB  - Religion and spirituality are known influences on medical providers' care of
      patients, but no studies have assessed resident beliefs related to patient
      perception of clinical care. The main objective of our study was to assess
      resident religious affiliation, religiosity, and spirituality in relation to self
      efficacy and communication with patients during adolescent clinic visits. We
      found that religious affiliation and religiosity appear to affect patient
      perception of communication with residents during adolescent visits; spirituality
      had little noted effect. Further research is warranted, especially regarding
      resident and patient gender correlations and differences in religious affiliation
      effects on patient perception of care.

PMID- 29058160
TI  - Equivalent Reduction in Greenhouse Gas Emissions by Mahayana Buddhists Practicing
      Vegetarian Diets.
AB  - The equivalent reduction in greenhouse gas emissions (GHGEs) by Mahayana
      Buddhists with vegetarian diets is quantitatively evaluated. The Buddhists in
      seven Mahayana-dominated countries or regions, i.e., China, Japan, Vietnam, South
      Korea, Taiwan, Hong Kong, and Singapore, are studied. Assessments of the
      vegetarian population among these Mahayana-dominated countries or regions are
      performed. Correlation formulas based on data from a national survey are
      developed to quantify the GHGEs of various dietary groups by using the meat
      consumption as the only required input. To demonstrate its reliability, the
      prediction from the formulas developed is first compared with the results of a
      food production-and-consumption study using a different approach. Then, the
      formulas are used to assess the GHGE reduction due to Mahayana Buddhists with
      vegetarian diets. The assessment indicates that Mahayana Buddhists with
      vegetarian diets account for the equivalent GHGE reduction of 48.83 million
      metric tons of carbon dioxide equivalent, which is a huge amount and is equal to
      11.3 or 8.9% of the GHGEs from France or the UK in 2012, respectively.

PMID- 29058161
TI  - Developing an Islamic Research Ethics Framework.
AB  - In surveying the medical literature on Islamic principles of research ethics, it
      is apparent that attempts to identify ethical principles are replete with issues
      of standards and gaps in knowledge of the uses of scriptural sources. Despite
      this, attempts at creating an Islamic ethical framework for research ethics may
      improve current practices in research in Muslim-majority countries and contribute
      to the growing canon of secular bioethics. This paper aims to identify principles
      and considerations within Islam that (1) overlap with current corpora on research
      ethics, and (2) further informs the current research ethics discourse.

PMID- 29058162
TI  - Correction to: Impact of a Structural Intervention to Address Alcohol Use Among
      Gay Bar Patrons in San Francisco: The PACE Study.
AB  - The original version of this article contains an omission in the list of authors
      for Dr. Adam W. Carrico. The corrected authors list for the article is given in
      this erratum.

PMID- 29058163
TI  - Pilot Evaluation of the Ability of Men Who Have Sex with Men to Self-Administer
      Rapid HIV Tests, Prepare Dried Blood Spot Cards, and Interpret Test Results,
      Atlanta, Georgia, 2013.
AB  - In the United States, an estimated 67% of new HIV diagnoses are among men who
      have sex with men (MSM), however 25% of HIV-positive MSM in the 2014 National HIV
      Behavioral Surveillance Survey were unaware of their infection. HIV self-testing
      (HIVST) with rapid diagnostic tests (RDTs) may facilitate access to HIV testing.
      We evaluated the ability of 22 MSM to conduct two HIV RDTs (OraQuick (r) In-Home
      HIV Test and a home-use prototype of Sure Check (r) HIV 1/2 Assay), interpret
      sample images of test results, and collect a dried blood spot (DBS) specimen.
      While some participants did not follow every direction, most participants were
      able to conduct HIVST and correctly interpret their results. Interpretation of
      panels of RDT images was especially difficult when the "control" line was
      missing, and 27% of DBS cards produced were rated as of bad quality.
      Modifications to the DBS instructions were necessary prior to evaluating the
      performance of these tests in real-world settings.

PMID- 29058164
TI  - Hand-assisted laparoscopic Hassab's procedure for esophagogastric varices with
      portal hypertension.
AB  - BACKGROUND: Laparoscopic surgery for patients with portal hypertension is
      considered to be contraindicated because of the high risk of massive
      intraoperative hemorrhaging. However, recent reports have shown hand-assisted
      laparoscopic surgery for devascularization and splenectomy to be a safe and
      effective method of treating esophagogastric varices with portal hypertension.
      The aim of this study is to evaluate the efficacy of hand-assisted laparoscopic
      devascularization and splenectomy (HALS Hassab's procedure) for the treatment of
      esophagogastric varices with portal hypertension. CASE PRESENTATION: From 2009 to
      2016, seven patients with esophagogastric varices with portal hypertension were
      treated with hand-assisted laparoscopic devascularization and splenectomy in our
      institute. Four men and three women with a median age of 61 years (range 35-71)
      were enrolled in this series. We retrospectively reviewed the medical records for
      the perioperative variables, postoperative mortality and morbidity, and
      postoperative outcomes of esophagogastric varices. The median operative time was
      455 (range 310-671) min. The median intraoperative blood loss was 695 (range 15
      2395) ml. The median weight of removed spleen was 507 (range 242-1835) g. The
      conversion rate to open surgery was 0%. The median postoperative hospital stay
      was 21 (range 13-81) days. During a median 21 (range 3-43) months of follow-up,
      the mortality rate was 0%. Four postoperative complications (massive ascites,
      enteritis, intra-abdominal abscess, and intestinal ulcer) were observed in two
      patients. Those complications were treated successfully without re-operation.
      Esophagogastric varices in all patients disappeared or improved. Bleeding from
      esophagogastric varices was not observed during the follow-up period. CONCLUSION:
      Although our data are preliminary, hand-assisted laparoscopic devascularization
      and splenectomy proved an effective procedure for treating esophagogastric
      varices in patients with portal hypertension.

PMID- 29058165
TI  - Clinical characteristics and risk factors associated with mortality in calcific
      uremic arteriolopathy.
AB  - BACKGROUND: Calcific uremic arteriolopathy (CUA) is an often-fatal condition in
      dialysis patients. The clinical descriptions and treatments of CUA patients have
      been confined mostly to case reports. We report a comprehensive characterization
      of CUA and its associated diagnosis, treatment patterns, and outcome. METHODS: An
      internet-based registry collected information about CUA in dialysis patients.
      Univariate analysis using Cox proportional hazards models estimated hazard ratios
      of the association between clinical characteristics, laboratory values, and
      treatments with all-cause mortality. RESULTS: A total of 117 CUA patients had
      adequate information for analysis. The majority of patients (56.7%) were
      diagnosed clinically, with only 32.5% biopsied. Debridement was undertaken in
      42.6% of cases. Intravenous sodium thiosulfate (STS) was initiated in 54.7% of
      patients; most received >= 12.5 g of STS (98.3%) for < 3 months (79.7%). Mean
      parathyroid hormone (PTH) and phosphorus (P) were 459 +/- 492 pg/mL and 6.3 +/-
      2.1 mg/dL, respectively. A total of 24 patients (21.6%, of 111 with information)
      died, with a median survival time of 2.9 months. In univariate analysis, higher
      mortality was observed in patients with cardiovascular disease (CVD; HR = 10.47;
      95% CI 1.40-78.38), those taking warfarin at time of diagnosis (HR = 2.74; 95% CI
      1.16-6.51), and those who had both diabetes (DM) and CVD and who were taking
      warfarin (HR = 13.41; 95% CI 1.66-109.29). CONCLUSIONS: In real-world clinical
      practice, there is substantial variability in the diagnosis and treatment of CUA.
      There is usually only modest derangement of bone and mineral parameters at the
      time of diagnosis. Death is common. The presence of CVD and use of warfarin may
      influence clinical outcome after diagnosis of CUA.

PMID- 29058166
TI  - Association between uremic toxin-anthranilic acid and fibrinolytic system
      activity in predialysis patients at different stages of chronic kidney disease.
AB  - PURPOSE: Chronic kidney disease (CKD) is an estimated risk factor for increased
      mortality and morbidity due to fibrinolytic system disturbances. Progressive loss
      of renal function leads to retention of uremic toxins. Anthranilic acid (AA) is a
      tryptophan-derived uremic toxin with multidirectional properties that can affect
      the hemostatic system. The goal of this study was to examine the association
      between AA and the parameters of fibrinolysis at different stages of CKD.
      METHODS: Patients with CKD were divided into two groups: mild-to-moderate (n =
      20) and severe-to-end-stage CKD (n = 28). Seventeen healthy volunteers served as
      an additional control group. Parameters of fibrinolysis, inflammation, and
      monocytes activation were determined by ELISA immune-enzymatic kits. AA levels
      were evaluated using high-performance liquid chromatography. RESULTS: AA
      concentration and parameters of fibrinolysis: urokinase-type plasminogen
      activator (uPA), its soluble receptor (suPAR), tissue plasminogen activator
      (tPA), tissue plasminogen activator inhibitor-1 (PAI-1) and plasmin-antiplasmin
      complex (PAP) were significantly elevated in the CKD groups compared with the
      controls. The markers of inflammation, monocyte activation, and impaired kidney
      function were also increased in those with CKD. AA was positively correlated with
      the uPA/suPAR system in the early stages of CKD, whereas during severe-to-end
      stage CKD, inverse relationships were observed between AA, tPA and PAI-1.
      Additionally, AA was an independent variable associated with tPA in patients with
      CKD overall and with uPA levels in the mild-to-moderate CKD group. CONCLUSIONS:
      Obtained results suggest for the first time the association between AA and the
      fibrinolytic system in CKD patients. The distinct relationship between AA and
      individual parameters of fibrinolysis appears to be dependent on CKD stage.

PMID- 29058167
TI  - A Meta-analytical Synthesis and Examination of Pathological and Problem Gambling
      Rates and Associated Moderators Among College Students, 1987-2016.
AB  - The problem of gambling addiction is especially noteworthy among college
      students, many of whom have the resources, proximity, free time, and desire to
      become involved in the myriad options of gambling now available. Although limited
      attention has been paid specifically to college student gambling in the body of
      literature, there have been three published meta-analyses estimating the
      prevalence of probable pathological gambling among college students. The research
      presented is the largest and most comprehensive, presenting an up-to-date
      proportion of those students worldwide exhibiting gambling pathology as assessed
      by the South Oaks Gambling Screen, and is the first to include estimates of sub
      clinical problem gambling. A thorough literature review and coding procedure
      resulted in 124 independent data estimates retrieved from 72 studies conducted
      between 1987 and the present, surveying 41,989 university students worldwide. The
      estimated proportion of probable pathological gamblers among students was
      computed at 6.13%, while the rate of problem gambling was computed at 10.23%.
      Statistical significance was found in the influence of the percentage of non
      white students on pathological gambling rates. The implications of this and other
      moderator analyses such as age and year of studies, as well as recommendations
      for future practice in dealing with college students and gambling disorder on
      campus are outlined and described in detail. Suggestions and rationales for
      future avenues of research in the area are also described.

PMID- 29058169
TI  - Chronic Exercise Reduces CETP and Mesterolone Treatment Counteracts Exercise
      Benefits on Plasma Lipoproteins Profile: Studies in Transgenic Mice.
AB  - Regular exercise and anabolic androgenic steroids have opposing effects on the
      plasma lipoprotein profile and risk of cardio-metabolic diseases in humans.
      Studies in humans and animal models show conflicting results. Here, we used a
      mice model genetically modified to mimic human lipoprotein profile and
      metabolism. They under-express the endogenous LDL receptor gene (R1) and express
      a human transgene encoding the cholesteryl ester transfer protein (CETP),
      normally absent in mice. The present study was designed to evaluate the
      independent and interactive effects of testosterone supplementation, exercise
      training and CETP expression on the plasma lipoprotein profile and CETP activity.
      CETP/R1 and R1 mice were submitted to a 6-week swimming training and mesterolone
      (MEST) supplementation in the last 3 weeks. MEST treatment increased markedly LDL
      levels (40%) in sedentary CETP/R1 mice and reduced HDL levels in exercised R1
      mice (18%). A multifactorial ANOVA revealed the independent effects of each
      factor, as follows. CETP expression reduced HDL (21%) and increased non-HDL (15%)
      fractions. MEST treatment increased the VLDL concentrations (42%) regardless of
      other interventions. Exercise training reduced triacylglycerol (25%) and free
      fatty acids (20%), increased both LDL and HDL (25-33%), and reduced CETP (19%)
      plasma levels. Significant factor interactions showed that the increase in HDL
      induced by exercise is explained by reducing CETP activity and that MEST blunted
      the exercise-induced elevation of HDL-cholesterol. These results reinforce the
      positive metabolic effects of exercise, resolved a controversy about CETP
      response to exercise and evidenced MEST potency to counteract specific exercise
      benefits.

PMID- 29058170
TI  - PAM, OLA, and LNA are Differentially Taken Up and Trafficked Via Different
      Metabolic Pathways in Porcine Adipocytes.
AB  - Dietary fatty acids have different effects on fat deposition in pigs. To clarify
      the underlying mechanisms of this difference, we compared the metabolism of
      palmitic (PAM, saturated), oleic (OLA, monounsaturated) and linoleic acid (LNA,
      polyunsaturated) in porcine adipocytes treated with 100 MUM PAM, OLA or LNA. We
      observed that the adipocytes incubated with LNA accumulated more lipids compared
      with those treated with PAM and OLA. We then probed the metabolism of these fatty
      acids in porcine adipocytes by using isotope-labelled fatty acids. The results
      showed that 42% of the [1-14C] LNA, 34% of the [1-14C] PAM and 28% of the [1-14C]
      OLA were recovered in the cellular lipids. The gene expression analyses showed
      that LNA significantly increased the expression of adipogenesis- and oxidation
      related genes including PPARgamma, C/EBPalpha, ap2 and NRF1. In addition, the
      cells incubated with LNA showed a decreased Ser112 phosphorylation in PPARgamma
      compared to those incubated with PAM and OLA. Furthermore, when PPARgamma Ser112
      phosphorylation was inhibited, no significant difference in the triacylglycerol
      contents in the adipocytes was observed. These results showed the dietary fatty
      acids had different metabolism pathways in porcine adipocytes, and LNA
      significantly promoted lipid accumulation, probably by regulating PPARgamma
      phosphorylation in adipocytes.

PMID- 29058168
TI  - Cognitive Deficits in Executive Functions and Decision-Making Impairments Cluster
      Gambling Disorder Sub-types.
AB  - To identify Gambling Disorder (GD) subtypes, in a population of men seeking
      treatment for GD, according to specific executive function domains (i.e.,
      cognitive flexibility, inhibition and working memory as well as decision making)
      which are usually impaired in addictive behaviors. A total of 145 males ranging
      from 18 to 65 years diagnosed with GD were included in this study. All
      participants completed: (a) a set of questionnaires to assess psychopathological
      symptoms, personality and impulsivity traits, and (b) a battery of
      neuropsychological measures to test different executive functioning domains. Two
      clusters were identified based on the individual performance on the
      neuropsychological assessment. Cluster 1 [n = 106; labeled as Low Impaired
      Executive Function (LIEF)] was composed by patients with poor results in the
      neuropsychological assessment; cluster 2 patients [n = 46; labeled as High
      Impaired Executive Function (HIEF)] presented significantly higher deficits on
      the assessed domains and performed worse than the ones of LIEF cluster. Regarding
      the characterization of these two clusters, patients in cluster 2 were
      significantly older, unemployed and registered higher mean age of GD onset than
      patients in cluster 1. Additionally, patients in cluster 2 also obtained higher
      psychopathological symptoms, impulsivity (in both positive and negative urgency
      as well as sensation seeking) and some specific personality traits (higher harm
      avoidance as well as lower self-directedness and cooperativeness) than patients
      in cluster 1. The results of this study describe two different GD subtypes based
      on different cognitive domains (i.e., executive function performance). These two
      GD subtypes display different impulsivity and personality traits as well as
      clinical symptoms. The results provide new insight into the etiology and
      characterization of GD and have the potential to help improving current
      treatments.

PMID- 29058171
TI  - Cavitary Pulmonary Sporotrichosis: Case Report and Literature Review.
AB  - A case of cavitary pulmonary sporotrichosis without mucocutaneous involvement
      caused by Sporothrix schenckii is reported in a sexagenarian woman with a long
      smoking history. The patient was hospitalized for septic shock with multiorgan
      failure from a respiratory focus. The diagnosis was delayed due to the fungal
      etiological agent was not initially considered in the differential diagnosis. A
      good clinical and radiological evolution was obtained with the antifungal
      therapy. Occasional cases of primary pulmonary sporotrichosis have been reported
      in the literature. Due to its low incidence, this is a less-known and
      underestimated clinical form. Both clinical suspicion and microbiological studies
      are needed to reach pulmonary sporotrichosis diagnosis.

PMID- 29058172
TI  - The Expression of Dectin-1, Irak1 and Rip2 During the Host Response to
      Aspergillus fumigatus.
AB  - BACKGROUND: C-type lectin receptors (CLRs), Toll-like receptors (TLRs), and Nod
      like receptors (NLRs) have the ability to recognize Aspergillus fumigatus (A.
      fumigates) and induce innate immune response. Dectin-1 is a well-described CLR,
      while interleukin-1 receptor-associated kinase 1 (Irak1) and receptor-interacting
      protein 2 (Rip2) are pivotal adaptor proteins of TLRs and NLRs signaling
      pathways, respectively. OBJECTIVES: Our primary aim is to elucidate whether
      Dectin-1 regulates the expression of Irak1 and Rip2, and confirm that CLRs, TLRs,
      and NLRs pathways act synergistically in response to A. fumigatus infection.
      METHODS: Pulmonary infection mouse models were established. Myeloid cells were
      differentiated in cell culture and examined by inverted microscopy, flow
      cytometry, and scanning electron microscopy. The relative mRNA levels were
      determined by qRT-PCR. The protein expression levels were determined by
      immunohistochemistry and Western blot. RESULTS: The expression of Dectin-1,
      Irak1, Rip2, and phosphorylation level of nuclear factor (NF)-kappaB p65 were
      induced by conidia in immunocompetent mice, while their expression and
      phosphorylation level were inhibited in immunocompromised mice after the
      administration of conidia. Conidia increased the expression of Dectin-1, Irak1,
      and Rip2 in myeloid cells, while Dectin-1 silencing significantly reduced their
      expression. CONCLUSION: Our findings demonstrate that Dectin-1, Irak1, and Rip2
      are involved in response to A. fumigatus infection. Dectin-1 modulates the
      expression of Irak1 and Rip2. Additionally, these three signaling pathways are
      interconnected, and CLRs pathway plays a dominant role against A. fumigatus
      invasion.

PMID- 29058173
TI  - Cardiovascular morbidity and mortality in patients with rheumatic disease:
      hyperuricemia, a forgotten puzzle piece?

PMID- 29058174
TI  - Does the elevation of CAMLs predict metastatic breast cancer patients' survival?

PMID- 29058176
TI  - Demonstration of subcellular migration of CK2alpha localization from nucleus to
      sarco(endo)plasmic reticulum in mammalian cardiomyocytes under hyperglycemia.
AB  - The cellular control of glucose uptake and glycogen metabolism in mammalian
      tissues is in part mediated through the regulation of protein-serine/threonine
      kinases including CK2. Although it participates to several cellular signaling
      processes, however, its subcellular localization is not well-defined while some
      documents mentioned its localization change under pathological conditions. The
      activation/phosphorylation of some proteins including Zn2+-transporter ZIP7 in
      cardiomyocytes is controlled with CK2alpha, thereby, inducing changes in the
      level of intracellular free Zn2+ ([Zn2+] i ). In this regard, we aimed to examine
      cellular localization of CK2alpha in cardiomyocytes and its possible subcellular
      migration under hyperglycemia. Our confocal imaging together with biochemical
      analysis in isolated sarco(endo)plasmic reticulum [S(E)R] and nuclear fractions
      from hearts have shown that CK2alpha localized highly to S(E)R and Golgi and
      weakly to nuclear fractions in physiological condition. However, it can migrate
      from nuclear fractions to S(E)R under hyperglycemia. This migration can further
      underlie phosphorylation of a target protein ZIP7 as well as some endogenous
      kinases and phosphatases including PKA, CaMKII, and PP2A. We also have shown that
      CK2alpha activation is responsible for hyperglycemia-associated [Zn2+] i increase
      in diabetic heart. Therefore, our present data demonstrated, for the first time,
      the physiological relevance of CK2alpha in cellular control of Zn2+-distribution
      via inducing ZIP7 phosphorylation and activation of these above endogenous actors
      in hyperglycemia/diabetes-associated cardiac dysfunction. Moreover, our present
      data also emphasized the multi-subcellular compartmental localizations of
      CK2alpha and a tightly regulation of these localizations in cardiomyocytes.
      Therefore, taken into consideration of all data, one can emphasize the important
      role of the subcellular localization of CK2alpha as a novel target-pathway for
      understanding of diabetic cardiomyopathy.

PMID- 29058177
TI  - Cross tolerance in beet armyworm: long-term selection by cadmium broadens
      tolerance to other stressors.
AB  - Long lasting exposure of animals to stressing factor may lead to the selection of
      population able to cope with the stressor at lower cost than unexposed
      individuals. The aim of this study was to assess whether 130-generational
      selection of a beet armyworm to cadmium in food might have induced tolerance also
      to other stressors. The potential tolerance was assessed by means of unspecific
      stress markers: HSP70 concentration, DNA damage level, and energy budget indices
      in L5 larval instars of beet armyworm. The animals originated from Cd-exposed and
      control strains exposed additionally in a short-term experiment to high/low
      temperature or pesticide-spinosad. The application of the additional stressors
      caused, in general, an increase in the levels of studied parameters, in a strain
      dependent manner. The most significant increase was found in HSP70 level in the
      individuals from the Cd-strain exposed to various spinosad concentration.
      Therefore, multigenerational contact with cadmium caused several changes that
      enable the insect to survive under a chronic stress, preparing the organism to
      the contact with an additional, new stressor. This relationship may be described
      as a sort of cross tolerance. This may, possibly, increase the probability of
      population survivorship and, at the same time, decrease the efficiency of
      pesticide-based plant protection efforts.

PMID- 29058175
TI  - Ribociclib with letrozole vs letrozole alone in elderly patients with hormone
      receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2
      trial.
AB  - PURPOSE: Determine the efficacy and safety of first-line ribociclib plus
      letrozole in elderly patients with HR+, HER2- advanced breast cancer. METHODS:
      668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior
      systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2
      trial (NCT01958021); 295 patients were aged >= 65 years. Patients were randomized
      to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or
      placebo plus letrozole until disease progression, unacceptable toxicity, death,
      or treatment discontinuation. The primary endpoint was PFS, which was evaluated
      in elderly (>= 65 years) and younger (< 65 years) patients. Secondary endpoints
      included response rates and safety. RESULTS: Ribociclib plus letrozole
      significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio:
      0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI
      0.378-0.723). Overall response rates were numerically higher in the ribociclib vs
      placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in
      elderly patients, with the safety profile similar to the overall study
      population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in
      the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups;
      most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue
      were > 10% more frequent in the ribociclib plus letrozole vs placebo plus
      letrozole arm and discontinuation rates were similar in both arms. CONCLUSIONS:
      Addition of ribociclib to letrozole is a valid therapeutic option for elderly
      patients with HR+, HER2- advanced breast cancer in the first-line setting.

PMID- 29058179
TI  - Manipulating Potassium Channel Expression and Function in Hippocampal Neurons by
      In Utero Electroporation.
AB  - In utero electroporation (IUE) of plasmid DNA into specific brain regions such as
      hippocampus and cortex has made it possible to reduce protein expression levels
      or even replace the endogenous protein with site-directed mutant proteins to
      reveal important physiological consequences. For example, shRNA can mediate
      targeted knockdown, and can be complemented by simultaneously expressing the
      shRNA immune wild-type protein to validate on-target effects, or by expression of
      an shRNA-immune protein harboring site-specific mutations. More recently, IUE has
      been adapted to express CRISPR/Cas9 components for targeted gene editing that
      abolishes protein expression. Utilizing these approaches via IUE results in
      transfected neurons that are interspersed with non-transfected control neurons in
      the same brain slices, allowing for direct comparisons. Because IUE is performed
      late in embryonic development and is confined to a relatively small percentage of
      neurons, developmental compensatory mechanisms that may compromise gene targeting
      via germ line transmission are minimized. Thus, IUE presents a powerful
      opportunity to rapidly and cost-effectively dissect molecular and cellular
      physiology in the context of the intact brain.

PMID- 29058178
TI  - Developmental exposure to the SSRI citalopram causes long-lasting behavioural
      effects in the three-spined stickleback (Gasterosteus aculeatus).
AB  - Selective Serotonin re-uptake inhibitors (SSRIs) are a class of psychotropic
      drugs used to treat depression in both adolescents and pregnant or breast-feeding
      mothers as well as in the general population. Recent research on rodents points
      to long-lasting behavioural effects of pre- and perinatal exposure to SSRIs which
      last into adulthood. In fish however, studies on effects of developmental
      exposure to SSRIs appears to be non-existent. In order to study effects of
      developmental SSRI exposure in fish, three-spine sticklebacks were exposed to 1.5
      ug/l of the SSRI citalopram in the ambient water for 30 days, starting two days
      post-fertilisation. After approximately 100 days of remediation in clean water
      the fish were put through an extensive battery of behavioural tests. Feeding
      behaviour was tested as the number of bites against a piece of food and found to
      be increased in the exposed fish. Aggression levels were measured as the number
      of bites against a mirror image during 10 min and was also found to be
      significantly increased in the exposed fish. Novel tank behaviour and locomotor
      activity was tested in an aquarium that had a horizontal line drawn half-way
      between the bottom and the surface. Neither the latency to the first transition
      to the upper half, nor the number of transitions or the total time spent in the
      upper half was affected by treatment. Locomotor activity was significantly
      reduced in the exposed fish. The light/dark preference was tested in an aquarium
      where the bottom and walls were black on one side and white on the other. The
      number of transitions to the white side was significantly reduced in the exposed
      fish but there was no effect on the latency to the first transition or the total
      time spent in the white half. The results in the current study indicate that
      developmental SSRI exposure causes long-lasting behavioural effects in fish and
      contribute to the existing knowledge about SSRIs as environmental pollutants.

PMID- 29058180
TI  - Studying KCNQ1 Mutation and Drug Response in Type 1 Long QT Syndrome Using
      Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
AB  - Patient-specific human induced pluripotent stem cell (hiPSC)-derived
      cardiomyocytes (hiPSC-CMs) are becoming a valuable model for studying inherited
      cardiac arrhythmias. Type 1 long-QT syndrome is associated with the genetic
      variants of KCNQ1 gene that encodes Kv7.1, the alpha-subunit of the voltage-gated
      potassium channel QKT subfamily member 1 that channels the slow component of the
      outwardly rectifying K+ channel current in cardiac myocytes. Patient- or disease
      specific hiPSC-CM model could facilitate the characterization of the genotype
      phenotype relationships and testing of individualized drug responses.Here, we
      describe the methods in the generation of hiPSC-CMs, molecular and
      electrophysiological characterizations of their cellular phenotypes associated
      with KCNQ1/Kv7.1 defects, and evaluation of the effects of K+ channel-specific
      drugs.

PMID- 29058181
TI  - Monitoring Changes in the Abundance of Endogenously Expressed ATP-Sensitive
      Potassium (KATP) Channels in the Plasma Membrane Using Surface Biotinylation.
AB  - The conductance of KATP channel activity can be regulated by gating and/or
      surface expression. Gating analysis is usually performed by electrophysiological
      recording. Analysis of surface KATP channel expression levels requires cell
      fractionation, protein separation, and quantification. Cell fractionation
      involves time-consuming high-speed centrifugation steps and skilled techniques
      for taking out specific layers. Moreover, contamination of intracellular
      membranes can confound results. Although commercial kits have been developed to
      make it easier for scientists, qualities of these kits vary which can give rise
      to variable results. Detection of membrane proteins using surface biotinylation
      technique consists of labeling cell surface proteins with a biotin reagent before
      lysing the cells, and isolating these tagged proteins by NeutrAvidin pulldown.
      Then, the samples are subjected to SDS-PAGE separation, transferred to PVDF
      membranes, and probed with specific antibodies. Quantification of cell surface
      expression is accomplished by densitometric measurement of the bands
      corresponding to the protein of interest and subsequent normalization by a
      membrane protein (as control). This alternative method for detecting expression
      of surface protein is relatively easy in steps and more economical in comparison
      to other methods such as cell fractionation.

PMID- 29058182
TI  - Nonsense-Mediated mRNA Decay of hERG Mutations in Long QT Syndrome.
AB  - Long QT syndrome type 2 (LQT2) is caused by mutations in the human ether-a-go-go
      related gene (hERG), which encodes the Kv11.1 potassium channel in the heart.
      Over 30% of identified LQT2 mutations are nonsense or frameshift mutations that
      introduce premature termination codons (PTCs). Contrary to intuition, the
      predominant consequence of LQT2 nonsense and frameshift mutations is not the
      production of truncated proteins, but rather the degradation of mutant mRNA by
      nonsense-mediated mRNA decay (NMD), an RNA surveillance mechanism that
      selectively eliminates the mRNA transcripts that contain PTCs. In this chapter,
      we describe methods to study NMD of hERG nonsense and frameshift mutations in
      long QT syndrome.

PMID- 29058183
TI  - Probing Subunits Interactions in KATP Channels Using Photo-Crosslinking via
      Genetically Encoded p-Azido-L-phenylalanine.
AB  - Potassium channels are multimeric protein complexes regulated by diverse
      physiological and pharmacological ligands. The key to understanding mechanisms of
      channel regulation is the ability to detect structural changes associated with
      ligand binding. While high-resolution structural methods such as X-ray
      crystallography and single-particle cryo-electron microscopy offer direct
      visualization of channel structures, these methods do have limitations and may
      not be suitable for the question of interest. In this chapter, we describe the
      use of a photo-cross-linker unnatural amino acid, p-azido-L-phenylalanine, to
      probe interactions between two proteins, the sulfonylurea receptor 1 and the
      inwardly rectifying potassium channel Kir6.2, that form the ATP-sensitive
      potassium (KATP) channel complex in the absence or presence of ligands. The
      difference in the extent of crosslinking between a liganded state and unliganded
      state can be used as a readout of ligand-induced structural changes. We
      anticipate that the protocol described here will also be applicable for other
      potassium channels and protein complexes.

PMID- 29058184
TI  - Hyper-SUMOylation of K+ Channels in Sudden Unexplained Death in Epilepsy:
      Isolation and Primary Culture of Dissociated Hippocampal Neurons from Newborn
      Mice for Subcellular Localization.
AB  - The physiological characteristics of rat and murine hippocampal neurons are
      widely studied, especially because of the involvement of the hippocampus in
      learning, memory, and neurological functions. Primary cultures of hippocampal
      neurons are commonly used to discover cellular and molecular mechanisms in
      neurobiology. By isolating and culturing individual hippocampal neurons,
      neuroscientists are able to investigate the activity of neurons at the individual
      cell and single synapse level, and to analyze properties related to cellular
      structure, cellular trafficking, and individual protein subcellular localization
      or protein-protein interaction using a variety of biochemical techniques.
      Conclusions addressed from such research are critical for testing theories
      related to memory, learning, and neurological functions. Here, we will describe
      how to isolate and culture primary hippocampal cells from newborn mice. The
      hippocampus may be isolated from newborn mice in as short as 2 min, and the cell
      cultures can be maintained for up to 2 weeks, and then ready for investigation of
      subcellular localization of K+ channel proteins and interaction with SUMO
      specific protease 2 (SENP2). The protocol provides a fast and efficient technique
      for the culture of neuronal cells from mouce hippocampal tissue, and will ensure
      the immunocytochemistry detection of subcellular localization or protein-protein
      interactions in neurological research.

PMID- 29058185
TI  - Simultaneous Real-Time Measurement of the beta-Cell Membrane Potential and Ca2+
      Influx to Assess the Role of Potassium Channels on beta-Cell Function.
AB  - Stimulus-secretion coupling in pancreatic beta-cells requires Ca2+ influx through
      voltage-dependent Ca2+ channels, whose activity is controlled by the plasma
      membrane potential (V m). Here, we present a method of measuring fluctuations in
      the beta-cell V m and Ca2+ influx simultaneously, which provides valuable
      information about the ionic signaling mechanisms that underlie insulin secretion.
      This chapter describes the use of perforated patch clamp electrophysiology on
      cells loaded with a fluorescent intracellular Ca2+ indicator, which permits the
      stable recording conditions needed to monitor the V m and Ca2+ influx in beta
      cells. Moreover, this chapter describes the protocols necessary for the
      preparation of mouse and human islet cells for the simultaneous recording of V m
      and Ca2+ as well as determining the specific islet cell type assessed in each
      experiment.

PMID- 29058186
TI  - Methods for Characterizing Disease-Associated ATP-Sensitive Potassium Channel
      Mutations.
AB  - The ATP-sensitive potassium (KATP) channel formed by the inwardly rectifying
      potassium channel Kir6.2 and the sulfonylurea receptor 1 (SUR1) plays a key role
      in regulating insulin secretion. Genetic mutations in KCNJ11 or ABCC8 which
      encode Kir6.2 and SUR1 respectively are major causes of insulin secretion
      disorders: those causing loss of channel function lead to congenital
      hyperinsulinism, whereas those causing gain of channel function result in
      neonatal diabetes and in some cases developmental delay, epilepsy, and neonatal
      diabetes, referred to as the DEND syndrome. Understanding how disease mutations
      disrupt channel expression and function is important for disease diagnosis and
      for devising effective therapeutic strategies. Here, we describe a workflow
      including several biochemical and functional assays to assess the effects of
      mutations on channel expression and function.

PMID- 29058187
TI  - Thallium Flux Assay for Measuring the Activity of Monovalent Cation Channels and
      Transporters.
AB  - Monovalent cation channels are critically important for physiological processes
      ranging from the control of neuronal excitability to the maintenance of solute
      balance. Mutations in these channels are associated with a multiplicity of
      diseases and monovalent cation channel-modulating drugs are used as therapeutics.
      Techniques that allow the measurement of the activity of these ion channels are
      useful for exploring their many biological roles as well as enabling the
      discovery and characterization of ion channel modulators for the purposes of drug
      discovery. Although there are numerous techniques for measuring the activity of
      monovalent cation channels, the thallium flux assay technique is a widely used
      fluorescence-based approach. Described herein is a method for using the thallium
      flux technique for detecting and quantifying the activity of small-molecule
      potassium channel modulators in 384-well plates.

PMID- 29058188
TI  - Nuclear Magnetic Resonance Approaches for Characterizing Protein-Protein
      Interactions.
AB  - The gating of potassium ion (K+) channels is regulated by various kinds of
      protein-protein interactions (PPIs). Structural investigations of these PPIs
      provide useful information not only for understanding the gating mechanisms of K+
      channels, but also for developing the pharmaceutical compounds targeting K+
      channels. Here, we describe a nuclear magnetic resonance spectroscopic method,
      termed the cross saturation (CS) method, to accurately determine the binding
      surfaces of protein complexes, and its application to the investigation of the
      interaction between a G protein-coupled inwardly rectifying K+ channel and a G
      protein alpha subunit.

PMID- 29058189
TI  - Studying Mechanosensitivity of Two-Pore Domain K+ Channels in Cellular and
      Reconstituted Proteoliposome Membranes.
AB  - Mechanical force sensation is fundamental to a wide breadth of biology from the
      classic senses of touch, pain, hearing, and balance to less conspicuous
      sensations of proprioception, blood pressure, and osmolarity and basic aspects of
      cell growth, differentiation, and development. These diverse and essential
      systems use force-gated (or mechanosensitive) ion channels that convert
      mechanical stimuli into cellular electrical signals. TRAAK, TREK1, and TREK2 are
      K+-selective ion channels of the two-pore domain K+ (K2P) family that are
      mechanosensitive: they are gated open by increasing membrane tension. TRAAK and
      TREK channels are thought to play roles in somatosensory and other mechanosensory
      processes in neuronal and non-neuronal tissues. Here, we present protocols for
      three assays to study mechanical activation of these channels in cell membranes:
      (1) cell swelling, (2) cell poking, and (3) patched membrane stretching. Patched
      membrane stretching is also applicable to the study of mechanosensitive K2P
      channel activity in a cell-free system and a procedure for proteoliposome
      reconstitution and patching is also presented. These approaches are also readily
      applicable to the study of other mechanosensitive ion channels.

PMID- 29058190
TI  - Migration of PIP2 on KCNQ2 Surface Revealed by Molecular Dynamics Simulations.
AB  - Lipids and membrane proteins are the main components of cell membranes. Lipid
      protein interactions are dynamic because these interactions typically occur on
      shallow protein surface clefts. Molecular dynamics (MD) simulations provide a
      tool for studying the dynamics of these interactions. Here, we describe the
      interactions of phosphatidylinositol-4,5-bisphosphate (PIP2) with both the open
      and closed states of a KCNQ2 channel. Through these methods, we show that a lipid
      can migrate between different binding sites in a protein and this migration
      modulates protein functions.

PMID- 29058191
TI  - Studying Structural Dynamics of Potassium Channels by Single-Molecule FRET.
AB  - Single-molecule FRET (smFRET) can visualize conformational dynamics of individual
      ion channels in lipid bilayers of defined composition. Dynamic and distance
      measurements from smFRET, combined with single channel recordings, can provide
      previously unattainable direct mechanistic insights into ion channel function and
      modulation. smFRET measurements require site-specific fluorophore labeling
      between two distinct sites, which is a major challenge for multimeric ion
      channels. This chapter aims to provide a step-by-step protocol: (1) to design
      concatemeric constructs with only two cysteine residues within a homotetrameric
      channel; (2) to express, purify, label, and reconstitute channel proteins; (3) to
      perform smFRET imaging on channel proteins in liposomes with an objective-based
      Total Internal Reflection (TIRF) microscope; and finally (4) to analyze the FRET
      distributions and dynamics that reflect the dynamic conformational transitions of
      ion channels in membranes.

PMID- 29058192
TI  - Patch-Clamp Recordings of the KcsA K+ Channel in Unilamellar Blisters.
AB  - Patch-clamp electrophysiology is the standard technique used for the high
      resolution functional measurements on ion channels. While studies using patch
      clamp are commonly carried out following ion channel expression in a heterologous
      system such as Xenopus oocytes or tissue culture cells, these studies can also be
      carried out using ion channels reconstituted into lipid vesicles. In this
      chapter, we describe the methodology for reconstituting ion channels into
      liposomes and the procedure for the generation of unilamellar blisters from these
      liposomes that are suitable for patch clamp. Here, we focus on the bacterial K+
      channel KcsA, although the methodologies described in this chapter should be
      applicable for the functional analysis of other ion channels.

PMID- 29058193
TI  - Combinatorial Assembly of Lumitoxins.
AB  - Ion channels are among the most important proteins in neuroscience and serve as
      drug targets for many brain disorders. During development, learning, disease
      progression, and other processes, the activity levels of specific ion channels
      are tuned in a cell-type specific manner. However, it is difficult to assess how
      cell-specific changes in ion channel activity alter emergent brain functions. We
      have developed a protein architecture for fully genetically encoded light
      activated modulation of endogenous ion channel activity. Fusing a genetically
      encoded photoswitch and an ion channel-modulating peptide toxin in a
      computationally designed fashion, this reagent, which we call Lumitoxins, can
      mediate light-modulation of specific endogenous ion channel activities in
      targeted cells. The modular lumitoxin architecture may be useful in a diversity
      of neuroscience tools. Here, we delineate how to construct lumitoxin genes from
      synthesized components, and provide a general outline for how to test their
      function in mammalian cell culture.

PMID- 29058194
TI  - Characterization of MC4R Regulation of the Kir7.1 Channel Using the Tl+ Flux
      Assay.
AB  - The family of inward rectifying potassium channels (Kir channels) plays crucial
      roles in the regulation of heart rhythms, renal excretion, insulin release, and
      neuronal activity. Their dysfunction has been attributed to numerous diseases
      such as cardiac arrhythmia, kidney failure and electrolyte imbalance, diabetes
      mellitus, epilepsy, retinal degeneration, and other neuronal disorders. We have
      recently demonstrated that the melanocortin-4 receptor (MC4R), a Galphas-coupled
      GPCR, regulates Kir7.1 activity through a mechanism independent of Galphas and
      cAMP. In contrast to the many other members of the Kir channel family, less is
      known about the biophysical properties, regulation, and physiological functions
      of Kir7.1. In addition to using conventional patch clamp techniques, we have
      employed a high-throughput Tl+ flux assay to further investigate the kinetics of
      MC4R-Kir7.1 signaling in vitro. Here, we discuss the employment of the Tl+ flux
      assay to study MC4R -mediated regulation of Kir7.1 activity and to screen
      compounds for drug discovery.

PMID- 29058195
TI  - Stopped-Flow Fluorometric Ion Flux Assay for Ligand-Gated Ion Channel Studies.
AB  - Quantitative investigations into functional properties of purified ion channel
      proteins using standard electrophysiological methods are challenging, in
      particular for the determination of average ion channel behavior following rapid
      changes in experimental conditions (e.g., ligand concentration). Here, we
      describe a method for determining the functional activity of liposome
      reconstituted K+ channels using a stopped-flow fluorometric ion flux assay.
      Channel activity is quantified by measuring the rate of fluorescence decrease of
      a liposome-encapsulated fluorophore, specifically quenched by thallium ions
      entering the liposomes via open channels. This method is well suited for studying
      the lipid bilayer dependence of channel activity, the activation and
      desensitization kinetics of ligand-dependent K+ channels, and channel modulation
      by channel agonists, blockers, or other antagonists.

PMID- 29058196
TI  - In Vivo Analysis of Potassium Channelopathies: Loose Patch Recording of Purkinje
      Cell Firing in Living, Awake Zebrafish.
AB  - Zebrafish is a lower vertebrate model organism that facilitates integrative
      analysis of the in vivo effects of potassium and other ion channel mutations at
      the molecular, cellular, developmental, circuit, systems, and behavioral levels
      of analysis. Here, we describe a method for extracellular, loose patch
      electrophysiological recording of electrical activity in cerebellar Purkinje
      cells in living, awake zebrafish, with the goal of investigating pathological
      mechanisms underlying channelopathies or other diseases that disrupt cerebellar
      function. Purkinje cell excitability and a functional cerebellar circuit develop
      rapidly in zebrafish and show strong conservation with the mammalian cerebellum.

PMID- 29058197
TI  - Site-Directed Unnatural Amino Acid Mutagenesis to Investigate Potassium Channel
      Pharmacology in Xenopus laevis Oocytes.
AB  - Unnatural amino acid mutagenesis is a useful tool enabling detailed investigation
      of ion channel structure-function relationships and pharmacology. Methods have
      been developed to apply this technique to different heterologous systems for
      electrophysiological studies, with each system offering unique advantages and
      limitations. Synthesis of aminoacylated-tRNA followed by injection into Xenopus
      laevis oocytes is beneficial because it allows for the incorporation of a wide
      range of unnatural sidechains, including amino acids with subtle structural
      differences. Here, we describe a protocol for unnatural amino acid mutagenesis
      implemented in our lab to study the pharmacology of KCNQ voltage-gated potassium
      channel opener compounds. This protocol should be applicable to other ion
      channels and receptor types amenable for functional studies in Xenopus laevis
      oocytes.

PMID- 29058198
TI  - Random Spherically Constrained Single-Particle (RSC) Method to Study Voltage
      Gated Ion Channels.
AB  - To study membrane protein structures using cryo-Electron Microscopy (cryo-EM),
      membrane proteins are usually extracted from cell membranes and solubilized in
      detergents. To restore the lipid bilayer environment of membrane proteins, a
      method called "random spherically constrained" (RSC) single-particle cryo-EM has
      been developed. The RSC platform establishes the lipid environment for membrane
      proteins and makes it possible, for the first time, to apply the desired
      transmembrane potential to trap voltage-gated ion channels in the desired
      functional states (e.g., deactivated voltage sensor at -120 mV) for structural
      analysis. No rupture or leakage was observed during the establishment of the
      transmembrane potential. The spherical geometry of liposomes is used as a
      constraint to accurately determine the orientation of the inserted membrane
      protein.

PMID- 29058199
TI  - CW-EPR Spectroscopy and Site-Directed Spin Labeling to Study the Structural
      Dynamics of Ion Channels.
AB  - Continuous-wave electron paramagnetic resonance spectroscopy (CW-EPR) and site
      directed spin labeling (SDSL) are proven experimental approaches to assess the
      structural dynamics of proteins in general (Hubbell et al., Curr Opin Struct Biol
      8(5):649-656, 1998; Kazmier et al., Curr Opin Struct Biol 45:100-108, 2016;
      Perozo et al., Science 285(5424):73-78, 1999). These techniques have been
      particularly effective assessing the structure of integral membrane proteins
      embedded in a lipid bilayer (Cortes et al., J Gen Physiol 117(2):165-180, 2001;
      Cuello et al., Science 306(5695):491-495, 2004; Dalmas et al., Structure
      18(7):868-878, 2010; Li et al., Proc Natl Acad Sci U S A 112(44):E5926-5935,
      2015; Perozo et al., J Gen Physiol 118(2):193-206, 2001), as well as determining
      the conformational changes associated with their biological function (Kazmier et
      al., Curr Opin Struct Biol 45:100-108, 2016; Perozo et al., Science 285(5424):73
      78, 1999; Arrigoni et al., Cell 164(5):922-936, 2016; Dalmas et al., Nat Commun
      5:3590, 2014; Dong et al., Science 308(5724):1023-1028, 2005; Farrens et al.,
      Science 274(5288):768-770, 1996; Perozo et al., Nat Struct Biol 5(6):459-469,
      1998; Perozo et al., Nature 418(6901):942-948, 2002). In this chapter, we
      described a practical guide for the spin-labeling, liposome reconstitution, and
      CW-EPR measurements of the prototypical bacterial K+ channel, KcsA.

PMID- 29058200
TI  - Ion Binding to Transport Proteins using Isothermal Titration Calorimetry.
AB  - Isothermal titration calorimetry (ITC) is an emerging, label-free technology used
      to measure ligand binding to membrane proteins. This technology utilizes a
      titration calorimeter to measure the heat exchange upon ligands binding to
      proteins, the magnitude of which is based on the overall enthalpy of the
      reaction. In this protocol, the steps we and others use to measure ion binding to
      ion transport proteins are described.

PMID- 29058201
TI  - Building Atomic Models of the Ion Channels Based on Low Resolution Electron
      Microscopy Maps and Homology Modeling.
AB  - Voltage-gated potassium channels play pivotal roles in excitable and non
      excitable cells. For many decades, structural properties and molecular mechanisms
      of these channels were inferred from functional observations. At the turn of the
      twenty-first century, structural biology revealed major aspects in the structural
      basis of ion channel organization, permeation, and gating. Among the available
      tools, homology modeling associated with low resolution microscopy helps in
      delineating the different structural elements of voltage-gated channels. Here, we
      describe in detail the methodology of homology modeling, using the 3D structure
      of the Kv2.1DeltaCTA ion channel as a reference.

PMID- 29058202
TI  - Studying Kv Channels Function using Computational Methods.
AB  - In recent years, molecular modeling techniques, combined with MD simulations,
      provided significant insights on voltage-gated (Kv) potassium channels intrinsic
      properties. Among the success stories are the highlight of molecular level
      details of the effects of mutations, the unraveling of several metastable
      intermediate states, and the influence of a particular lipid, PIP2, in the
      stability and the modulation of Kv channel function. These computational studies
      offered a detailed view that could not have been reached through experimental
      studies alone. With the increase of cross disciplinary studies, numerous
      experiments provided validation of these computational results, which endows an
      increase in the reliability of molecular modeling for the study of Kv channels.
      This chapter offers a description of the main techniques used to model Kv
      channels at the atomistic level.

PMID- 29058203
TI  - Low levels of lead and glutathione markers of redox status in human blood.
AB  - Exposure to lead (Pb) is implicated in a plethora of health threats in both
      adults and children. Increased exposure levels are associated with oxidative
      stress in the blood of workers exposed at occupational levels. However, it is not
      known whether lower Pb exposure levels are related to a shift toward a more
      oxidized state. To assess the association between blood lead level (BLL) and
      glutathione (GSH) redox biomarkers in a population of healthy adults, BLL and
      four GSH markers (GSH, GSSG, GSH/GSSG ratio and redox potential E h ) were
      measured in the blood of a cross-sectional cohort of 282 avid seafood-eating
      healthy adults living on Long Island (NY). Additionally, blood levels of two
      other metals known to affect GSH redox status, selenium (Se) and mercury (Hg),
      and omega-3 index were tested for effect modification. Regression models were
      further adjusted for demographic and smoking status. Increasing exposure to Pb,
      measured in blood, was not associated with GSSG, but was associated with lower
      levels of GSH/GSSG ratio and more positive GSH redox potential E h , driven by
      its association with GSH. No effect modification was observed in analyses
      stratified by Hg, Se, omega-3 index, sex, age, or smoking. Blood Pb is associated
      with lower levels of GSH and the GSH/GSSG ratio in this cross-sectional study of
      healthy adults.

PMID- 29058204
TI  - Valuing Healthcare Improvement: Implicit Norms, Explicit Normativity, and Human
      Agency.
AB  - I argue that greater attention to human agency and normativity in both
      researching and practicing service improvement may be one strategy for enhancing
      improvement science, illustrating with examples from cancer screening.
      Improvement science tends to deliberately avoid explicit normativity, for
      paradigmatically coherent reasons. But there are good reasons to consider
      including explicit normativity in thinking about improvement. Values and moral
      judgements are central to social life, so an adequate account of social life must
      include these elements. And improvement itself is unavoidably normative: it
      assumes that things could and should be better than they are. I seek to show that
      normativity will always be implicated in the creation of evidence, the design of
      programs, the practice of healthcare, and in citizens' judgements about that
      care, and to make a case that engaging with this normativity is worthwhile.

PMID- 29058206
TI  - Role of cardiovascular magnetic resonance in suspected cardiac amyloidosis: late
      gadolinium enhancement pattern as mortality predictor.
AB  - BACKGROUND: Cardiac magnetic resonance (CMR) has gained a central role in the
      diagnosis of cardiac amyloidosis (CA). While the diagnostic role of a typical
      late gadolinium enhancement (LGE) pattern (global subendocardial enhancement
      coupled with accelerated contrast washout) has been identified, evidence is still
      conflicting regarding the prognostic role of such examination. METHODS AND
      RESULTS: We retrospectively analysed all patients referring for CMR at Niguarda
      Hospital (Milan, Italy) from January 2006 to January 2015 for suspected CA.
      Primary outcome was all-cause mortality. We identified 42 patients and divided
      them into 2 groups, according to the presence (Group A) or absence (Group B) of a
      typical amyloidosis LGE pattern. At the end of the follow-up (median 37 months,
      interquartile range 10-50 months), 31 patients (74%) had died. The hazard ratio
      for all-cause death was 3.2 (95% confidence interval [CI] 1.5-6.4, p < 0.01) for
      Group A versus Group B. Median survival time was 17 months (95% CI 7-42 months)
      for Group A and 70 months (95% CI 49-94 months) for Group B (p < 0.01).
      Multivariate analysis did not find any adjunctive predictive role for
      biventricular volumes and ejection fraction, indexed left ventricular mass,
      transmitral E/e' at echocardiography, age at diagnosis or serum creatinine.
      CONCLUSION: In our population, a typical LGE pattern was significantly associated
      with higher mortality. Moreover, patients with a typical LGE pattern showed a
      globally worse prognosis. Our data suggest that the LGE pattern may play a
      central role in prognostic stratification of patients with suspected CA, thus
      prompting further diagnostic and therapeutic measures.

PMID- 29058205
TI  - Monocyte-mediated drug delivery systems for the treatment of cardiovascular
      diseases.
AB  - Major advances have been achieved in understanding the mechanisms and risk
      factors leading to cardiovascular disorders and consequently developing new
      therapies. A strong inflammatory response occurs with a substantial recruitment
      of innate immunity cells in atherosclerosis, myocardial infarction, and
      restenosis. Monocytes and macrophages are key players in the healing process that
      ensues following injury. In the inflamed arterial wall, monocytes, and monocyte
      derived macrophages have specific functions in the initiation and resolution of
      inflammation, principally through phagocytosis, and the release of inflammatory
      cytokines and reactive oxygen species. In this review, we will focus on delivery
      systems, mainly nanoparticles, for modulating circulating monocytes/monocyte
      derived macrophages. We review the different strategies of depletion or
      modulation of circulating monocytes and monocyte subtypes, using polymeric
      nanoparticles and liposomes for the therapy of myocardial infarction and
      restenosis. We will further discuss the strategies of exploiting circulating
      monocytes for biological targeting of nanocarrier-based drug delivery systems for
      therapeutic and diagnostic applications.

PMID- 29058207
TI  - Stroke risk in patients with device-detected atrial high-rate episodes.
AB  - Cardiovascular implantable electronic devices (CIEDs) can detect atrial
      arrhythmias, i. e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in
      patients showing AHRE appears to be lower than in patients with clinical atrial
      fibrillation (AF) and it is unclear whether the former will benefit from oral
      anticoagulants. Based on currently available evidence, it seems reasonable to
      consider antithrombotic therapy in patients without documented AF showing AHRE
      >24 hours and a CHA2DS2-VASc score (congestive heart failure, hypertension, age
      >=75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular
      disease, age 65-74 years and female sex) >=1, awaiting definite answers from
      ongoing randomised clinical trials. In patients with AHRE <24 hours, current
      literature does not support starting oral anticoagulation. In these patients,
      intensifying CIED read-outs can be considered to find progression in AHRE
      duration sooner, enhancing timely stroke prevention. The notion that AHRE and
      stroke coincide perseveres but should be abandoned since CIED data show a clear
      disconnect.

PMID- 29058208
TI  - Clinical correlates of trichuriasis diagnosed at colonoscopy.
AB  - Diagnosis of Trichuris trichiura infestations is usually based on identification
      of barrel-shaped ova in stool, but is frequently missed on stool microscopy. We
      describe the clinical profile of patients in whom Trichuris infection was
      incidentally diagnosed at colonoscopy. In a cross-sectional study, patients with
      colonoscopic diagnosis of trichuriasis were enrolled from the endoscopy unit in a
      tertiary care center. Blood and stool samples were collected from all those who
      were willing to participate and provide samples. Sixty-two patients participated,
      with mean (SD) age of 50.5 (13.6) years and male to female ratio of 40:22.
      Abdominal pain (61.2%) and/or altered bowel habits (32.2%) were the most common
      indication for colonoscopy. Most (66.6%) of the Trichuris were located in the
      cecum and ascending colon. Majority of the patients had live worms, either motile
      or adhering to the colonic mucosa. The number of worms was single or a few (<15)
      in 74.2% of patients. Out of 62 patients, 16 (25.8%) had relatively heavy load of
      parasites. Most patients had normal colonoscopic findings (80.6%).
      Periappendicular and/or cecal ulcerations/erosions were the most common (16.1%)
      abnormalities noted. Stool examination showed parasite ova only in four (6.4%)
      patients. In conclusion, colonoscopy was better than stool microscopy for the
      diagnosis of trichuriasis in our study.

PMID- 29058210
TI  - A plea to respect medical mistakes.

PMID- 29058209
TI  - The rs2910164 variant is associated with reduced miR-146a expression but not
      cytokine levels in patients with type 2 diabetes.
AB  - PURPOSE: Previous reports have demonstrated that genetic variations in microRNAs
      regulome could affect microRNAs-mediated regulation. Therefore, in the present
      study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral
      blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and
      controls, and (2) investigating the possible association of rs2910164 with miR
      146a and its related target genes expression and also serum cytokine levels.
      METHODS: The study population consisted of 60 subjects including 30 type 2
      diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164.
      The RNA expression levels were determined by real-time PCR. Moreover, TNF-alpha,
      IL-6, IL-10 and IL-1beta serum levels were measured using ELISA method. RESULTS:
      Our results showed that the miR-146a expression levels were significantly
      decreased in PBMCs (P = 0.004) and plasma (P = 0.008) samples of patients with
      T2D compared to healthy participants. In addition, we observed that IRAK1 mRNA
      expression-but not TLR4, TRAF6 and NFKB-was significantly increased in patients
      with T2D compared to controls (P = 0.028). The relative expression levels of miR
      146a in plasma and PBMCs samples of diabetic patients with the rs2910164 GG
      genotypes were significantly higher than that in CC (P < 0.05). Moreover, no
      significant differences were found in miR-146a targets and cytokine levels
      between the rs2910164 different genotypes. CONCLUSION: Our study demonstrated
      that miR-146a circulating levels were significantly elevated in controls compared
      with T2D patients. In addition, we identified that rs2910164-C allele is
      associated with reduced expression levels of the miR-146a but not its mRNAs
      targets and cytokine levels in diabetic patients.

PMID- 29058212
TI  - NAPR: a Cloud-Based Framework for Neuroanatomical Age Prediction.
AB  - The availability of cloud computing services has enabled the widespread adoption
      of the "software as a service" (SaaS) approach for software distribution, which
      utilizes network-based access to applications running on centralized servers. In
      this paper we apply the SaaS approach to neuroimaging-based age prediction. Our
      system, named "NAPR" (Neuroanatomical Age Prediction using R), provides access to
      predictive modeling software running on a persistent cloud-based Amazon Web
      Services (AWS) compute instance. The NAPR framework allows external users to
      estimate the age of individual subjects using cortical thickness maps derived
      from their own locally processed T1-weighted whole brain MRI scans. As a
      demonstration of the NAPR approach, we have developed two age prediction models
      that were trained using healthy control data from the ABIDE, CoRR, DLBS and NKI
      Rockland neuroimaging datasets (total N = 2367, age range 6-89 years). The
      provided age prediction models were trained using (i) relevance vector machines
      and (ii) Gaussian processes machine learning methods applied to cortical
      thickness surfaces obtained using Freesurfer v5.3. We believe that this
      transparent approach to out-of-sample evaluation and comparison of neuroimaging
      age prediction models will facilitate the development of improved age prediction
      models and allow for robust evaluation of the clinical utility of these methods.

PMID- 29058211
TI  - The Effects of One Amino Acid Substitutions at the C-Terminal Region of
      Thermostable L2 Lipase by Computational and Experimental Approach.
AB  - The substitutions of the amino acid at the predetermined critical point at the C
      terminal of L2 lipase may increase its thermostability and enzymatic activity, or
      even otherwise speed up the unfolding of the protein structure. The C-terminal of
      most proteins is often flexible and disordered. However, some protein functions
      are directly related to flexibility and play significant role in enzyme reaction.
      The critical point for mutation of L2 lipase structure was predicted at the
      position 385 of the L2 sequence, and the best three mutants were determined based
      on I-Mutant2.0 software. The best three mutants were S385E, S385I and S385V. The
      effects of the substitution of the amino acids at the critical point were
      analysed with molecular dynamics simulation by using Yet Another Scientific
      Artificial Reality Application software. The predicted mutant L2 lipases were
      found to have lower root mean square deviation value as compared to L2 lipase. It
      was indicated that all the three mutants had higher compactness in the structure,
      consequently enhanced the stability. Root mean square fluctuation analysis showed
      that the flexibility of L2 lipase was reduced by mutations. Purified S385E lipase
      had an optimum temperature of 80  degrees C in Tris-HCl pH 8. The highest
      enzymatic activity of purified S385E lipase was obtained at 80  degrees C
      temperature in Tris-HCl pH 8, while for L2 lipase it was at 70  degrees C in
      Glycine-NaOH pH 9. The thermal stability of S385V lipase was enhanced as compared
      to other protein since that the melting point (T m) value was at 85.96  degrees
      C. S385I lipase was more thermostable compared to recombinant L2 lipase and other
      mutants at temperature 60  degrees C within 16 h preincubation.

PMID- 29058213
TI  - How to Become a Smart Patient in the Era of Precision Medicine?
AB  - The objective of this paper is to define the definition of smart patients,
      summarize the existing foundation, and explore the approaches and system
      participation model of how to become a smart patient. Here a thorough review of
      the literature was conducted to make theory derivation processes of the smart
      patient; "data, information, knowledge, and wisdom (DIKW) framework" was
      performed to construct the model of how smart patients participate in the medical
      process. The smart patient can take an active role and fully participate in their
      own health management; DIKW system model provides a theoretical framework and
      practical model of smart patients; patient education is the key to the
      realization of smart patients. The conclusion is that the smart patient is
      attainable and he or she is not merely a patient but more importantly a captain
      and global manager of one's own health management, a partner of medical
      practitioner, and also a supervisor of medical behavior. Smart patients can
      actively participate in their healthcare and assume higher levels of
      responsibility for their own health and wellness which can facilitate the
      development of precision medicine and its widespread practice.

PMID- 29058214
TI  - Physiological Informatics: Collection and Analyses of Data from Wearable Sensors
      and Smartphone for Healthcare.
AB  - Physiological data from wearable sensors and smartphone are accumulating rapidly,
      and this provides us the chance to collect dynamic and personalized information
      as phenotype to be integrated to genotype for the holistic understanding of
      complex diseases. This integration can be applied to early prediction and
      prevention of disease, therefore promoting the shifting of disease care tradition
      to the healthcare paradigm. In this chapter, we summarize the physiological
      signals which can be detected by wearable sensors, the sharing of the
      physiological big data, and the mining methods for the discovery of disease
      associated patterns for personalized diagnosis and treatment. We discuss the
      challenges of physiological informatics about the storage, the standardization,
      the analyses, and the applications of the physiological data from the wearable
      sensors and smartphone. At last, we present our perspectives on the models for
      disentangling the complex relationship between early disease prediction and the
      mining of physiological phenotype data.

PMID- 29058215
TI  - Entropy for the Complexity of Physiological Signal Dynamics.
AB  - Recently, the rapid development of large data storage technologies, mobile
      network technology, and portable medical devices makes it possible to measure,
      record, store, and track analysis of biological dynamics. Portable noninvasive
      medical devices are crucial to capture individual characteristics of biological
      dynamics. The wearable noninvasive medical devices and the analysis/management of
      related digital medical data will revolutionize the management and treatment of
      diseases, subsequently resulting in the establishment of a new healthcare system.
      One of the key features that can be extracted from the data obtained by wearable
      noninvasive medical device is the complexity of physiological signals, which can
      be represented by entropy of biological dynamics contained in the physiological
      signals measured by these continuous monitoring medical devices. Thus, in this
      chapter I present the major concepts of entropy that are commonly used to measure
      the complexity of biological dynamics. The concepts include Shannon entropy,
      Kolmogorov entropy, Renyi entropy, approximate entropy, sample entropy, and
      multiscale entropy. I also demonstrate an example of using entropy for the
      complexity of glucose dynamics.

PMID- 29058216
TI  - Data Platform for the Research and Prevention of Alzheimer's Disease.
AB  - With the rapid increase in global aging, Alzheimer's disease has become a major
      burden in both social and economic costs. Substantial resources have been devoted
      to researching this disease, and rich multimodal data resources have been
      generated. In this chapter, we discuss an ongoing effort to build a data platform
      to harness these data to help research and prevention of Alzheimer's disease. We
      will detail this data platform in terms of its architecture, its data integration
      strategy, and its data services. Then, we will consider how to leverage this data
      platform to accelerate risk factor identification and pathogenesis study with its
      data analytics capability. This chapter will provide a concrete pathway for
      developing a data platform for studying and preventing insidious onset chronic
      diseases in this data era.

PMID- 29058217
TI  - Data Analysis for Gut Microbiota and Health.
AB  - In recent years, data mining and analysis of high-throughput sequencing of
      microbiomes and metagenomic data enable researchers to discover biological
      knowledge by characterizing the composition and variation of species across
      environmental samples and to accumulate a huge amount of data, making it feasible
      to infer the complex principle of species interactions. The interactions of
      microbes in a microbial community play an important role in microbial ecological
      system. Data mining provides diverse approachs to identify the correlations
      between disease and microbes and how microbial species coexist and interact in a
      host-associated or natural environment. This is not only important to advance
      basic microbiology science and other related fields but also important to
      understand the impacts of microbial communities on human health and diseases.

PMID- 29058218
TI  - Ontology-Based Vaccine Adverse Event Representation and Analysis.
AB  - Vaccine is the one of the greatest inventions of modern medicine that has
      contributed most to the relief of human misery and the exciting increase in life
      expectancy. In 1796, an English country physician, Edward Jenner, discovered that
      inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward
      Jenner and the history of smallpox and vaccination. Proceedings (Baylor
      University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide,
      we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine
      29:D7-D9, 2011). Other disabling and lethal diseases, like poliomyelitis and
      measles, are targeted for eradication (Bonanni, Vaccine 17:S120-S125,
      1999).Although vaccine development and administration are tremendously successful
      and cost-effective practices to human health, no vaccine is 100% safe for
      everyone because each person reacts to vaccinations differently given different
      genetic background and health conditions. Although all licensed vaccines are
      generally safe for the majority of people, vaccinees may still suffer adverse
      events (AEs) in reaction to various vaccines, some of which can be serious or
      even fatal (Haber et al., Drug Saf 32(4):309-323, 2009). Hence, the double-edged
      sword of vaccination remains a concern.To support integrative AE data collection
      and analysis, it is critical to adopt an AE normalization strategy. In the past
      decades, different controlled terminologies, including the Medical Dictionary for
      Regulatory Activities (MedDRA) (Brown EG, Wood L, Wood S, et al., Drug Saf
      20(2):109-117, 1999), the Common Terminology Criteria for Adverse Events (CTCAE)
      (NCI, The Common Terminology Criteria for Adverse Events (CTCAE). Available from:
      http://evs.nci.nih.gov/ftp1/CTCAE/About.html . Access on 7 Oct 2015), and the
      World Health Organization (WHO) Adverse Reactions Terminology (WHO-ART) (WHO, The
      WHO Adverse Reaction Terminology - WHO-ART. Available from: https://www.umc
      products.com/graphics/28010.pdf ), have been developed with a specific aim to
      standardize AE categorization. However, these controlled terminologies have many
      drawbacks, such as lack of textual definitions, poorly defined hierarchies, and
      lack of semantic axioms that provide logical relations among terms. A biomedical
      ontology is a set of consensus-based and computer and human interpretable terms
      and relations that represent entities in a specific biomedical domain and how
      they relate each other. To represent and analyze vaccine adverse events (VAEs),
      our research group has initiated and led the development of a community-based
      ontology: the Ontology of Adverse Events (OAE) (He et al., J Biomed Semant 5:29,
      2014). The OAE has been found to have advantages to overcome the drawbacks of
      those controlled terminologies (He et al., Curr Pharmacol Rep :1-16.
      doi:10.1007/s40495-016-0055-0, 2014). By expanding the OAE and the community
      based Vaccine Ontology (VO) (He et al., VO: vaccine ontology. In The 1st
      International Conference on Biomedical Ontology (ICBO-2009). Nature Precedings,
      Buffalo. http://precedings.nature.com/documents/3552/version/1 ; J Biomed Semant
      2(Suppl 2):S8; J Biomed Semant 3(1):17, 2009; Ozgur et al., J Biomed Semant
      2(2):S8, 2011; Lin Y, He Y, J Biomed Semant 3(1):17, 2012), we have also
      developed the Ontology of Vaccine Adverse Events (OVAE) to represent known VAEs
      associated with licensed vaccines (Marcos E, Zhao B, He Y, J Biomed Semant 4:40,
      2013).In this book chapter, we will first introduce the basic information of
      VAEs, VAE safety surveillance systems, and how to specifically query and analyze
      VAEs using the US VAE database VAERS (Chen et al., Vaccine 12(10):960-960, 1994).
      In the second half of the chapter, we will introduce the development and
      applications of the OAE and OVAE. Throughout this chapter, we will use the
      influenza vaccine Flublok as the vaccine example to launch the corresponding
      elaboration (Huber VC, McCullers JA, Curr Opin Mol Ther 10(1):75-85, 2008).
      Flublok is a recombinant hemagglutinin influenza vaccine indicated for active
      immunization against disease caused by influenza virus subtypes A and type B. On
      January 16, 2013, Flublok was approved by the FDA for the prevention of seasonal
      influenza in people 18 years and older in the USA. Now, more than 3 years later,
      an exploration of the reported AEs associated with this vaccine is urgently
      needed.

PMID- 29058219
TI  - LEMRG: Decision Rule Generation Algorithm for Mining MicroRNA Expression Data.
AB  - Recently, research on mining microRNA (or miRNA) expression data has received a
      lot of attention, mainly because of its role in gene regulation. However, such
      type of data - usually saved in the form of microarrays - are very specific,
      because they contain only a small number of cases (often less than 100) compared
      with large number of attributes (equal to several hundreds or even tens of
      thousand). The small number of cases available during the learning process can
      cause instability of the newly created classifiers. Secondly, the huge number of
      attributes imposes the necessity of selecting only a few dominant attributes
      strongly correlated with the decision. Thus, an application of fundamental
      machine learning approaches of mining microarray data and its further
      classification is problematic or even could just fail.Thus, the main goal of our
      research is to develop the generalized algorithm of mining microarray data
      (including miRNA data sets), mainly to improve stability and, consequently,
      accuracy of classification for the newly created learning classifiers. The main
      concept of the novel approach is based on iteratively inducing many subsequent
      decision rule sets - called decision rule generations - instead of inducing only
      a single decision rule set, as it is done routinely. The decision rules have been
      chosen as the baseline classifiers of the newly developed LEMRG (Learning from
      Examples Module based on Rule Generations) algorithm mainly because the decision
      rule-based knowledge representation is easier for humans to comprehend, rather
      than other learning models. In our research we used a miRNA expression level
      learning data set describing 11 types of human cancers, while the testing data
      set contained poorly differentiated cases of only four types of cancers. As
      expected, our new classifiers - saved in the form of so-called cumulative
      decision rule sets - had better stability and accuracy of classification than
      single decision rule sets induced in the traditional manner. Furthermore, the
      LEMRG was compared with other machine learning models. It was proven that only 3
      out of all 16 tested classifiers enabled so effective classification as our newly
      developed approach. Thus, using our cumulative set of decision rules, all cases
      of cancer from two selected concepts - colon and ovary - were correctly
      classified. Furthermore, we showed the role of these selected miRNAs as the
      potential biomarkers for diagnosis of tumors.A preliminary result of our research
      on decision rule generations was initially presented at the first International
      Conference of Digital Medicine and Medical 3D Printing (17-19.06.2016, Nanjing,
      China).

PMID- 29058220
TI  - Privacy Challenges of Genomic Big Data.
AB  - With the rapid advancement of high-throughput DNA sequencing technologies,
      genomics has become a big data discipline where large-scale genetic information
      of human individuals can be obtained efficiently with low cost. However, such
      massive amount of personal genomic data creates tremendous challenge for privacy,
      especially given the emergence of direct-to-consumer (DTC) industry that provides
      genetic testing services. Here we review the recent development in genomic big
      data and its implications on privacy. We also discuss the current dilemmas and
      future challenges of genomic privacy.

PMID- 29058221
TI  - Systems Health: A Transition from Disease Management Toward Health Promotion.
AB  - To date, most of the chronic diseases such as cancer, cardiovascular disease, and
      diabetes, are the leading cause of death. Current strategies toward disease
      treatment, e.g., risk prediction and target therapy, still have limitations for
      precision medicine due to the dynamic and complex nature of health. Interactions
      among genetics, lifestyle, and surrounding environments have nonnegligible
      effects on disease evolution. Thus a transition in health-care area is urgently
      needed to address the hysteresis of diagnosis and stabilize the increasing health
      care costs. In this chapter, we explored new insights in the field of health
      promotion and introduced the integration of systems theories with health science
      and clinical practice. On the basis of systems biology and systems medicine, a
      novel concept called "systems health" was comprehensively advocated. Two types of
      bioinformatics models, i.e., causal loop diagram and quantitative model, were
      selected as examples for further illumination. Translational applications of
      these models in systems health were sequentially discussed. Moreover, we
      highlighted the bridging of ancient and modern views toward health and put
      forward a proposition for citizen science and citizen empowerment in health
      promotion.

PMID- 29058222
TI  - Accuracy of the Garmin 920 XT HRM to perform HRV analysis.
AB  - Heart rate variability (HRV) analysis is widely used to investigate autonomous
      cardiac drive. This method requires periodogram measurement, which can be
      obtained by an electrocardiogram (ECG) or from a heart rate monitor (HRM), e.g.
      the Garmin 920 XT device. The purpose of this investigation was to assess the
      accuracy of RR time series measurements from a Garmin 920 XT HRM as compared to a
      standard ECG, and to verify whether the measurements thus obtained are suitable
      for HRV analysis. RR time series were collected simultaneously with an ECG
      (Powerlab system, AD Instruments, Castell Hill, Australia) and a Garmin XT 920 in
      11 healthy subjects during three conditions, namely in the supine position, the
      standing position and during moderate exercise. In a first step, we compared RR
      time series obtained with both tools using the Bland and Altman method to obtain
      the limits of agreement in all three conditions. In a second step, we compared
      the results of HRV analysis between the ECG RR time series and Garmin 920 XT
      series. Results show that the accuracy of this system is in accordance with the
      literature in terms of the limits of agreement. In the supine position, bias was
      0.01, - 2.24, + 2.26 ms; in the standing position, - 0.01, - 3.12, + 3.11 ms
      respectively, and during exercise, - 0.01, - 4.43 and + 4.40 ms. Regarding HRV
      analysis, we did not find any difference for HRV analysis in the supine position,
      but the standing and exercise conditions both showed small modifications.

PMID- 29058223
TI  - Protective effect of early low-dose hydrocortisone on ventilator-associated
      pneumonia in the cancer patients: a propensity score analysis.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is a care-related event that
      could be promoted by immune suppression caused by critical diseases, malignancies
      and cancer treatments. Low dose of hydrocortisone was proposed for modulation of
      immune response in the critically ill population. METHODS: In this monocentric
      observational study, all cancer patients mechanically ventilated for more than 48
      h were included. Effect of low-dose hydrocortisone administered during the first
      48 h of mechanical ventilation was evaluated applying inverse probability
      weighting analysis after propensity score assessment. VAP impact on 1-year
      mortality, ICU length of stay and mechanical ventilation duration was secondarily
      determined. RESULTS: Within this cohort, 190 cancer patients were followed. VAP
      was confirmed in 22.1% of cases in the early hydrocortisone group and confirmed
      in 42.6% of cases in the no or late hydrocortisone group. Early hydrocortisone
      exhibited a protective effect on the risk of VAP (OR 0.23; 95% CI 0.12-0.44; P <
      0.0001). VAP was associated with 1-year mortality (HR 1.60; 95% CI 1.10-2.34; P =
      0.017) and increased ICU length of stay (mean extra length of stay: 4.2 days; 95%
      CI 0.6-7.8). CONCLUSIONS: Immune modulation with low-dose hydrocortisone
      administered in the first days of mechanical ventilation could protect from VAP
      occurrence in cancer patients.

PMID- 29058224
TI  - Influence of region-of-interest determination on measurement of signal-to-noise
      ratio in liver on PET images.
AB  - OBJECTIVE: On 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography
      (PET), signal-to-noise ratio in the liver (SNRliver) is used as a metric to
      assess image quality. However, some regions-of-interest (ROIs) are used when
      measuring the SNRliver. The purpose of this study is to examine the different
      ROIs and volumes of interest (VOIs) to obtain a reproducible SNRliver. METHODS:
      This study included 108 patients who underwent 18F-FDG-PET/CT scans for the
      purpose of cancer screening. We examined four different ROIs and VOIs; a 3-cm
      diameter and a 4-cm-diameter circular ROI and a 3-cm-diameter and a 4-cm-diameter
      spherical VOI on the right lobe of the patients' livers. The average of SUV
      (SUVmean), standard deviation (SD) of SUV (SUVSD), SNRliver and SD of the
      SNRliver obtained using ROIs and VOIs were then compared. RESULTS: Although the
      SUVmean was not different among the ROIs and VOIs, the SUVSD was small with a 3
      cm-diameter ROI. The largest SUVSD was obtained with a 4-cm-diameter spherical
      VOI. The SNRliver and the SD of the SNRliver with a 4-cm-diameter spherical VOI
      were the smallest, while those with a 3-cm-diameter circular ROI were the
      largest. These results suggest that a small ROI may be placed on a relatively
      homogeneous region not representing whole liver unintentionally. CONCLUSION: The
      SNRliver varied according to the shape and size of ROIs or VOIs. A 4-cm-diameter
      spherical VOI is recommended to obtain stable and reproducible SNRliver.

PMID- 29058225
TI  - The Case for Transitioning to Pass/Fail Grading on Psychiatry Clerkships.

PMID- 29058228
TI  - MALDI Imaging Mass Spectrometry of N-glycans and Tryptic Peptides from the Same
      Formalin-Fixed, Paraffin-Embedded Tissue Section.
AB  - Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry
      (IMS) is a unique and well developed tool for probing the protein content of
      formalin-fixed, paraffin-embedded tissue (FFPE). Integral to this approach is the
      application of trypsin, and more recently peptide N-glycosidase F, to release
      tryptic peptides or N-glycans from tissue and report localization of distinct
      species. This is typically done on serial or adjacent tissue sections, and there
      is an emerging need to understand the colocalized protein population linked to
      the exact same regions of N-glycans. Here we describe an approach where N-glycans
      are first imaged from a tissue section followed by reprocessing of the same
      tissue section for tryptic peptide MALDI IMS. Strategies for colocalizing
      peptides to target N-glycans or N-glycan regions are described.

PMID- 29058227
TI  - Circulating levels of proinflammatory mediators as potential biomarkers of post
      traumatic knee osteoarthritis development.
AB  - BACKGROUND: The identification of biomarkers of post-traumatic osteoarthritis
      (PTOA) progression is of clinical importance. The aims of this study were: (1) to
      assess the abilities of various soluble proinflammatory mediators in plasma to
      distinguish patients with knee PTOA from controls; (2) to determine the
      correlations between the mediators in plasma and those mediators in synovial
      fluid (SF); and (3) to explore the associations of the mediators with
      radiographic PTOA severity. MATERIALS AND METHODS: The concentrations of IL
      1beta, IL-6, IL-18, TNFalpha, and leptin were measured using ELISA. Nitric oxide
      was determined as nitrite/nitrate (NO x ) using the Griess reaction. RESULTS: We
      included 171 subjects (134 PTOA patients and 37 controls) and excluded patients
      with rheumatoid arthritis or gout. The ROC curve of plasma NO x had the highest
      AUC, a specificity of 100%, and a sensitivity of 84.4%. The combination of IL-6
      and leptin proved to be the most discriminatory, with an AUC value of 0.933, a
      specificity of 96.7%, and a sensitivity of 85.7%. The levels of NO x , IL-6, IL
      18, and leptin in plasma were significantly correlated with their levels in SF.
      Leptin levels in both plasma (p = 0.036) and SF (p = 0.041) and the synovial IL
      18 level (p = 0.045) were correlated with the Kellgren-Lawrence (KL) grade. Early
      stage PTOA (KL 1-2) was associated with a high concentration of IL-1beta in
      plasma before and after (OR 6.235, 95% CI 1.362 to 28.552, p = 0.018) adjusting
      for age, gender, and BMI. CONCLUSIONS: Circulating NO x level and a combination
      of IL-6 and leptin permitted the strongest discrimination of patients with PTOA
      from controls. PTOA severity was correlated with leptin levels in plasma and SF
      and with the synovial IL-18 level. Early PTOA was associated with the circulating
      level of IL-1beta. LEVEL OF EVIDENCE: III (case-control study).

PMID- 29058226
TI  - Clinical guidelines for the prevention and treatment of osteoporosis: summary
      statements and recommendations from the Italian Society for Orthopaedics and
      Traumatology.
AB  - BACKGROUND: The Italian Society for Orthopaedics and Traumatology conceived this
      guidance-which is primarily addressed to Italian orthopedic surgeons, but should
      also prove useful to other bone specialists and to general practitioners-in order
      to improve the diagnosis, prevention, and treatment of osteoporosis and its
      consequences. MATERIALS AND METHODS: Literature reviews by a multidisciplinary
      team. RESULTS: The following topics are covered: the role of instrumental,
      metabolic, and genetic evaluations in the diagnosis of osteoporosis; appraisal of
      the risk of fracture and thresholds for intervention; general strategies for the
      prevention and treatment of osteoporosis (primary and secondary prevention); the
      pharmacologic treatment of osteoporosis; the setting and implementation of
      fracture liaison services for tertiary prevention. Grade A, B, and C
      recommendations are provided based on the main levels of evidence (1-3).
      Toolboxes for everyday clinical practice are provided. CONCLUSIONS: The first up
      to-date Italian guidelines for the primary, secondary, and tertiary prevention of
      osteoporosis and osteoporotic fractures are presented.

PMID- 29058229
TI  - Synthesis of functionalized dispiro[indoline-3,1[Formula: see text]-cyclopentane
      3[Formula: see text],3[Formula: see text]-indolines] via cyclodimerization of 3
      phenacylideneoxindolines with benzoylhydrazides and arylhydrazines.
AB  - The triethylamine-promoted domino cyclodimerization reaction of 3
      phenacylideneoxindolines with benzohydrazides in acetonitrile afforded densely
      substituted dispiro[indoline-3,1[Formula: see text]-cyclopentane-3[Formula: see
      text],3[Formula: see text]-indolines] in good yields and with high
      diastereoselectivity. The similar domino reaction of 3-phenacylideneoxindoles
      with arylhydrazines also gave corresponding dispiro[indoline-3,1[Formula: see
      text]-cyclopentane-3[Formula: see text],3[Formula: see text]-indolines] with
      hydrazinyl or arylazo groups according to the structures of arylhydrazines.

PMID- 29058230
TI  - A facile and regioselective one-pot synthesis of novel pyrazolo[1[Formula: see
      text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinoline-2,3-dicarboxylate hybrids
      via intramolecular Wittig reaction.
AB  - The regioselective syntheses of novel pyrazolo[1[Formula: see text],5[Formula:
      see text]:1,2]pyrrolo[3,4-b]quinoline-2,3-dicarboxylates (6a-l) from pyrrolo([3,4
      b]quinolin-2(3H)-yl)benzamides through an intramolecular Wittig reaction are
      described. This protocol takes advantages of mild conditions, simple workup and
      high yield which make this method attractive for the synthesis of these hybrid of
      pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinolines.

PMID- 29058231
TI  - Computational design of new protein kinase D 1 (PKD1) inhibitors: homology-based
      active site prediction, energy-optimized pharmacophore, docking and database
      screening.
AB  - Protein kinase D 1 (PKD1) overexpression has a well-validated role in cancer
      progression and its inhibitors have defined a protective role-play of PKD1 for
      various cancers such as prostate, pancreatic and noninvasive breast cancers, and
      more. Therefore, the current research was aimed at designing new PKD1 inhibitors
      combining different ligand- and structure-based computational drug designing
      methodologies. Initially, the three-dimensional structure of PKD1's active site
      was computationally modeled, corrected using molecular dynamic simulations and
      validated for docking experiments. The highest active PKD1 inhibitor was used to
      develop a structure-based energetic pharmacophore (e-pharmacophore) model, and a
      final model was selected with five structural features (Pmodel_AADHR).
      Pmodel_AADHR was validated and used for database screening to obtain new hits
      against PKD1. These newly retrieved hits were docked against our PKD1 protein
      model, and those displaying essential interactions are reported herein as new
      hits, which could serve as new leads for cancer research, especially pancreatic
      cancer.

PMID- 29058232
TI  - Iterative model reconstruction (IMR) algorithm for reduced radiation dose renal
      artery CT angiography with different tube voltage protocols.
AB  - PURPOSE: To investigate the image quality (IQ) of reduced radiation dose (RRD)
      renal artery CT angiography (CTA) using iterative model reconstruction (IMR)
      algorithm at different tube voltage. METHODS: Renal artery CTA scans were
      acquired with a 256-MDCT scanner on 84 patients assigned into four groups. Group
      4 was scanned as standard radiation dose (SRD) group: 120 kVp, automatic tube
      current modulation (ATCM) technique with an Image Quality Index of 20, and
      filtered back projection (FBP) algorithm. Tube voltage for three RRD groups was
      80 kVp in group 1, 100 kVp in group 2, and 120 kVp in group 3, and all three
      groups were with image quality index of 18 and IMR algorithm. Image noise, signal
      to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured. Subjective
      evaluation including diagnostic confidence, vessel artifact and intravascular
      contrast were performed. The effective radiation dose was recorded. RESULTS:
      Effective radiation dose was reduced in three RRD groups compared to group 4.
      Intravascular contrast was significantly better in group 1 and 2 than in group 3,
      and artifacts decreased in group 2 than in group 3 (P < 0.05). Vascular SNR, CNR
      and image noise improved in three IMR groups than those in FBP group (P < 0.05).
      Furthermore, among three IMR groups, group 1 and 2 achieved better objective
      evaluation than group 3 (P < 0.05). CONCLUSIONS: IMR along with RRD for renal
      artery CTA improved image quality compared to SRD protocol using FBP. On top of
      that, lower tube voltage tended to be more optimal.

PMID- 29058234
TI  - Does Size Matter? Correlation of Excised Gastric Specimen Size in Sleeve
      Gastrectomy to Postoperative Weight Loss and Comorbidities.
AB  - BACKGROUND: We present the correlation between excised specimen size in
      laparoscopic sleeve gastrectomy and patient demographics, comorbidities, and
      postoperative weight loss. OBJECTIVE: This study aims to address whether the size
      of gastric specimen excised during laparoscopic sleeve gastrectomy has any
      correlation with patient demographics, comorbidities, and postoperative percent
      of excess body weight lost. SETTING: Study was performed at a community teaching
      hospital in Michigan. METHODS: We examined data from 204 patients who underwent
      sleeve gastrectomy between August 2011 and January 2015. Data was collected
      retrospectively including demographics, comorbidities, body mass index (BMI),
      percent of excess body weight lost, and the size of the gastric specimen removed
      including specimen volume in cubic centimeters, length, width, and thickness in
      centimeters. RESULTS: We found that gastric specimen size does not correlate with
      initial BMI or change in BMI at 3, 6, or 12 months. Larger specimen sizes were
      found in males, increasing age, and patients with diabetes mellitus. CONCLUSIONS:
      There was no correlation between excised stomach size in laparoscopic sleeve
      gastrectomy and postoperative weight loss (percent of excess body weight lost) or
      change in BMI. Male gender, diabetes, and increasing patients' age correlated
      with larger excised stomach size. Initial BMI and having histological gastritis
      did not correlate with excised stomach size.

PMID- 29058233
TI  - Apparent diffusion coefficient for prediction of parametrial invasion in cervical
      cancer: a critical evaluation based on stratification to a Likert scale using T2
      weighted imaging.
AB  - PURPOSE: To evaluate the value of apparent diffusion coefficient (ADC) for
      determining parametrial invasion (PMI) in cervical cancer, by stratifying them
      into subgroups based on a Likert scale using T2-weighted imaging (T2WI).
      MATERIALS AND METHODS: This retrospective study included 87 patients with FIGO
      stage IA2-IIB cervical cancer who underwent preoperative MRI followed by radical
      hysterectomy. Radiological PMI was assessed on T2WI using a six-point Likert
      scale and ADC values of the tumors were measured. MRI findings were compared
      between patients with and without PMI. Differences in ADC according to the Likert
      scale were also assessed. RESULTS: 19 (21.8%) patients had pathological PMI. The
      prevalence of PMI was significantly associated with Likert scale (P < 0.001). ADC
      values significantly differed according to Likert scale (P < 0.001). However,
      only tumors with a Likert score of 0 (MRI-invisible) had significantly greater
      ADC than others (P < 0.001) while no significant difference was observed among
      tumors with Likert scores of 1-5 (P = 0.070-0.889). Patients with PMI had
      significantly lower ADC values than those without PMI (P = 0.034). However, no
      significant difference was seen between patients with and without PMI within each
      Likert score group (P = 0.180-0.857). CONCLUSION: T2WI-based Likert score for
      radiological PMI and ADC values of the tumor were significantly associated with
      pathological PMI. However, the apparent association seen between ADC values and
      PMI may be due to contribution of high ADC values of MRI-invisible tumors rather
      than reflecting their relationship.

PMID- 29058235
TI  - Risk of Metformin-Associated Lactic Acidosis (MALA) in Patients After Gastric
      Bypass Surgery.
AB  - BACKGROUND: Pharmacokinetic data suggest that the risk of metformin-associated
      lactic acidosis (MALA) may be increased after Roux-en-Y gastric bypass (RYGB)
      surgery. The aim of this study was to examine the impact of metformin on plasma
      lactate levels before and after RYGB surgery. METHODS: Retrospective study of
      plasma lactate levels before and 3 months after RYGB surgery in patients with
      type 2 diabetes mellitus (T2DM) not using metformin (MET-0, N = 58), on a stable
      dose (MET-S, N = 138), or on a decreasing dose (MET-D, N = 85) of metformin.
      RESULTS: Preoperatively, lactate levels were similar in patients on metformin
      (1.8 +/- 0.05 mmol/L) and those not on metformin (1.7 +/- 0.08 mmol/L), P = 0.21.
      Three months postoperatively, lactate levels had decreased in all groups (P <
      0.001) to 1.3 +/- 0.07 (SE), 1.4 +/- 0.05, and 1.2 +/- 0.05 mmol/l in MET-0, MET
      S, and MET-D, respectively. Lactate levels differed between the groups (P =
      0.03), with the lowest level in MET-D. The number of patients with
      hyperlactatemia (lactate > 2 mmol/l) decreased from 31 to 14%, from 22 to 8.6%,
      and from 26 to 4.7% in MET-S, MET-0, and MET-D, respectively. CONCLUSION: Mild
      hyperlactatemia (lactate > 2 mmol/l) is common in morbidly obese patients with
      T2DM. It is probably related to increase lactate production by adipocytes.
      Lactate levels decreased after RYGB-induced weight loss, irrespective of the use
      of metformin. We therefore conclude that there is no need for routinely lowering
      of the metformin dose after uncomplicated RYGB surgery, as long as normal renal
      function is preserved.

PMID- 29058236
TI  - Postoperative Care and Functional Recovery After Laparoscopic Sleeve Gastrectomy
      vs. Laparoscopic Roux-en-Y Gastric Bypass Among Patients Under ERAS Protocol.
AB  - BACKGROUND: The most commonly performed bariatric procedures are laparoscopic
      sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). There
      are major differences between LSG and LRYGB during postoperative period.
      Optimization of the postoperative care may be achieved by using enhanced recovery
      after surgery (ERAS) protocol, which allows earlier functional recovery. PURPOSE:
      The aim was to assess differences in the course of postoperative care conducted
      in accordance with ERAS protocol among patients after LSG and LRYGB. MATERIAL AND
      METHODS: Data concerning patients treated for morbid obesity were prospectively
      gathered in one academic center. Patients were divided into two groups: LSG (n =
      364, 63.41%) and LRYGB (n = 210, 36.59%). Multiple factors were used as endpoints
      to determine the influence of the type of bariatric procedure on postoperative
      course. RESULTS: The rate of postoperative nausea and vomiting and incidence of
      intravenous fluid administration during the operation was higher in LSG group.
      LRYGB patients were able to tolerate higher oral fluid intake volumes during the
      first and the second postoperative day. Mean diuresis during the second and the
      third postoperative day was significantly higher in LRYGB group. Administration
      of diuretics and painkillers was comparable between groups, while the risk of
      fever after the operation was higher in LRYGB group. Mean length of stay was
      higher in LSG group (LRYGB vs. LSG, 3.46 days +/- 1.58 vs. 3.64 days +/- 4.41, p
      = 0.039). CONCLUSIONS: In our opinion, postoperative treatment after LSG requires
      more supervision and longer time until functional recovery is achieved.

PMID- 29058237
TI  - Cardiac Remodeling Patterns in Severe Obesity According to Arterial Hypertension
      Grade.
AB  - PURPOSE: The purpose of this study is to correlate the left ventricular
      hypertrophy (LVH) patterns according to severe obesity and arterial hypertension
      (AHT) grades. METHODS: A cross-sectional prospective study was conducted in 379
      patients with severe obesity. Obesity was classified according to the BMI in the
      following: morbidly obese (MO; 40 < BMI < 50 kg/m2) and super obese (SO; BMI > 50
      kg/m2). The AHT was classified into classes 1 and 2 according to American Heart
      Association. The presence of LVH and the pattern of cardiac remodeling were
      determined by transthoracic echocardiography. RESULTS: LVH was present in 58.6%
      of patients. Obesity and AHT had additive effects in LVH prevalence. LVH was
      found in 32.9 and 46.7% of MO with AHT grades 1 and 2, respectively. LVH was
      diagnosed in 39.1% in SO with AHT grade 1 and in 50% of AHT grade 2. Patients
      with AHT presented a significantly higher risk of developing LVH (OR 1.97; p =
      0.003). Hypertension grade was also a determinant variable in the development of
      LVH. Patients with AHT 2 had 4.31-fold greater risk (p < 0.001) when compared to
      normotensive patients. BMI was only considered an independent risk factor for LVH
      in patients with BMI greater than 47.17 kg/m2 (OR 1.62; p = 0.023). CONCLUSION:
      AHT is a stronger predictive factor of LVH than obesity grade.

PMID- 29058239
TI  - Low-Purine Diet Is More Effective Than Normal-Purine Diet in Reducing the Risk of
      Gouty Attacks After Sleeve Gastrectomy in Patients Suffering of Gout Before
      Surgery: a Retrospective Study.
AB  - BACKGROUND: Obese patients with preoperative gout often suffer of gouty attacks
      after bariatric surgery (BS), probably due to the lack of an adequate
      postoperative diet. OBJECTIVES: The objectives of the study are to assess whether
      sleeve gastrectomy (SG) is effective in reducing the frequency of gouty attacks
      and also whether a postoperative low-purine diet (LPD) may further reduce these
      attacks as compared to a normal-purine diet (NPD) in a series of patients
      suffering of gout before SG. METHODS: In this retrospective study, we measured
      and compared total body weight (TBW), body mass index (BMI), uric acid levels
      (UAL), anti-gout medication (allopurinol) requirements, and frequency in gouty
      attacks in 40 patients that underwent SG and who received either a LPD (n = 24)
      or NPD (n = 16). Compliance in following the prescribed diet was assessed in both
      groups study. RESULTS: Before surgery, LPD and NPD patients had hyperuricemia and
      were receiving allopurinol. One year after SG, LPD and NPD groups showed a
      significant decrease in serum UAL (p < 0.001 and p = 0.00175, respectively).
      However, serum UAL decreased more significantly with the LPD compared to the NPD
      (p < 0.001). Furthermore, while NPD group showed a significant decrease in
      allopurinol requirements (p = 0.00130) and on the frequency in gouty attacks (p <
      0.001), LPD group were off allopurinol therapy and had no gouty attacks 12 months
      after SG. Both groups showed high compliance in following the prescribed diets.
      CONCLUSION: LPD is more effective in reducing the frequency of gouty attacks
      after SG compared with NPD in patients suffering of gout before surgery.

PMID- 29058240
TI  - How Can We Manage Long-Term Follow-up After Obesity and Metabolic Surgery?

PMID- 29058238
TI  - Bariatric Surgery Resistance: Using Preoperative Lifestyle Medicine and/or
      Pharmacology for Metabolic Responsiveness.
AB  - Bariatric surgery is an effective and durable treatment for individuals with
      obesity and its associated comorbidities. However, not all patients meet weight
      loss and/or cardiometabolic goals following bariatric surgery, suggesting that
      some people are bariatric surgery resistant. The reason for this resistance is
      unclear, but potential factors, such as adiposity-derived inflammation, insulin
      resistance, hyperglycemia, and aerobic fitness prior to surgery, have been
      related to blunted surgery responsiveness. Exercise, diet, and/or pharmacology
      are effective at reducing inflammation and improving insulin action as well as
      physical function. Herein, we present data that supports the novel hypothesis
      that intervening prior to surgery can enhance disease resolution in people who
      are resistant to bariatric surgery.

PMID- 29058241
TI  - The Factors Affecting Lower Urinary Tract Functions in Patients Undergoing
      Laparoscopic Sleeve Gastrectomy.
AB  - BACKGROUND: We prospectively assessed changes in the lower urinary system
      functions of women with morbid obesity following laparoscopic sleeve gastrectomy
      and the factors affecting these changes. METHODS: Data from 40 females who had
      undergone laparoscopic sleeve gastrectomy due to morbid obesity (body mass index,
      BMI >= 40 kg/m2) between January 2014-2016 at S.B.U. Bursa Yuksek Ihtisas
      Training and Research Hospital were prospectively evaluated. The presence of
      comorbidities, onset of obesity, smoking, American Society of Anesthesiologists
      (ASA) score, pre and 12-month postoperative weights and BMIs, fasting blood
      glucose (FBG), blood urea nitrogen, creatinine, insulin, homeostatic model
      assessment-insulin resistance (HOMA-IR) test results, overactive bladder survey
      (OAB-Q) scores, volume of urination, and Qmax values obtained from uroflowmetry
      studies were recorded and assessed. RESULTS: Statistically significant
      differences in weight, BMI, FBG, insulin, HOMA-IR score and creatinine values pre
      operation, and the corresponding values obtained at 12 months post-operation were
      observed (all, p < 0.001). OAB-Q scores were observed to be statistically
      significantly lower in the postoperative period relative to those in the
      preoperative period (p < 0.001). Urination volume was statistically significantly
      higher during the postoperative period (p = 0.048) than during the preoperative
      period. Non-smoking patients showed a reduction in OAB-Q score and a
      statistically significant increase in urination volume during the postoperative
      period (p < 0.001, p = 0.011, respectively); smoking patients indicated a
      statistically significant reduction in OAB-Q score only during the postoperative
      period; however, urination volume was not statistically significant between two
      groups (p = 0.013, p = 0.303). In patients with an ASA score of 1, preoperative
      OAB-Q scores were statistically significantly lower (p = 0.035) than those
      obtained post-operation. Patients with childhood-onset obesity showed
      statistically significantly increased urination volumes during postoperative
      period in comparison with values obtained pre-operation (p = 0.042). CONCLUSION:
      Improvements in lower urinary system functions were affected by patient-related
      factors, such as comorbidity, obesity onset, smoking, ASA score, and weight loss,
      following laparoscopic sleeve gastrectomy.

PMID- 29058243
TI  - Orbital fat volume in the inferolateral quadrant in Japanese: a guide for orbital
      fat decompression without injury to the oculomotor nerve.
AB  - PURPOSE: The inferior oblique muscle branch of the oculomotor nerve is
      susceptible to injury during orbital fat removal from the inferolateral quadrant
      of the orbit. Understanding the amount of removable orbital fat volume in this
      quadrant may be helpful in achieving maximum fat decompression without causing
      nerve injury. The aim of this study was to calculate the orbital fat volume in
      the inferolateral quadrant using computed tomographic (CT) images. METHODS: In
      this retrospective, observational study, contiguous 1-mm coronal CT images were
      obtained from 53 sides (30 patients). The cross-sectional areas of the orbital
      fat in the inferolateral quadrant were measured from the level just behind the
      inferior oblique muscle to the orbital apex. The cross-sectional areas reached
      the inferior oblique muscle branch medially, the lateral orbital wall laterally,
      the inferior edge of the lateral rectus muscle superiorly, and the orbital floor
      inferiorly. An integrated value between the cross-sectional areas and the CT
      slice thickness was calculated. RESULTS: The mean orbital fat volume in the
      inferolateral quadrant was 3.9 +/- 1.4 mL (range: 1.3-7.0 mL). Multiple
      regression analysis demonstrated a significant relationship between orbital fat
      volume and Hertel exophthalmometry measurement (adjusted r 2 = 0.101; P = 0.012),
      although the thickness of the lateral and inferior recti muscles was deleted from
      the regression equation by stepwise process. CONCLUSIONS: The orbital fat volume
      in the inferolateral quadrant can serve as a guide for orbital fat removal
      without causing injury to the inferior oblique muscle nerve branch.

PMID- 29058244
TI  - Long-term outcomes of Ahmed tube implantation in pediatric glaucoma after
      multiple surgeries.
AB  - PURPOSE: To report success of Ahmed glaucoma valve (AGV) implantation in eyes
      with pediatric glaucoma and subconjunctival scarring from previous surgeries.
      METHODS: A retrospective review of pediatric glaucoma patients who underwent AGV
      implantation after >= 2 previous surgeries with conjunctival scarring.
      Preoperative and postoperative parameters were recorded to study success, defined
      as intraocular pressure (IOP) < 22 mmHg with or without medications and without
      serious complications. RESULTS: Eleven eyes of 10 patients were included, and the
      mean age was 12.7 years. Diagnoses included primary childhood glaucoma, aphakic
      glaucoma, and anterior segment anomalies. Mean number of prior ocular surgeries
      was 3.3 (+/- 1.3). Final mean IOP was 17.5 (+/- 4.3) mmHg, significantly
      different from the preoperative mean of 24.8 (+/- 6.8) mmHg, p = 0.01. Mean
      number of anti-glaucoma medications also decreased significantly from 2.8 (+/-
      1.5) to 1.4 (+/- 1.5), p = 0.02. The success rate was 82% at a mean follow-up of
      51.6 (+/- 10.8) months. Complications were minor and transient. CONCLUSION:
      Subconjunctival scarring did not increase the risk of failure of tube shunt
      surgery.

PMID- 29058242
TI  - Effect of Myostatin SNP on muscle fiber properties in male Thoroughbred horses
      during training period.
AB  - Variants of the Myostatin gene have been shown to have an influence on muscle
      hypertrophy phenotypes in a wide range of mammalian species. Recently, a
      Thoroughbred horse with a C-Allele at the g.66493737C/T single-nucleotide
      polymorphism (SNP) has been reported to be suited to short-distance racing. In
      this study, we examined the effect of the Myostatin SNP on muscle fiber
      properties in young Thoroughbred horses during a training period. To investigate
      the effect of the Myostatin SNP on muscle fiber before training, several mRNA
      expressions were relatively quantified in biopsy samples from the middle gluteal
      muscle of 27 untrained male Thoroughbred horses (1.5 years old) using real-time
      RT-PCR analysis. The remaining muscle samples were used for immunohistochemical
      analysis to determine the population and area of each fiber type. All
      measurements were revaluated in biopsy samples of the same horses after a 5-month
      period of conventional training. Although the expressions of Myostatin mRNA
      decreased in all SNP genotypes, a significant decrease was found in only the C/C
      genotype after training. While, expression of VEGFa, PGC1alpha, and SDHa mRNAs,
      which relate to the biogenesis of mitochondria and capillaries, was significantly
      higher (54-82%) in the T/T than the C/C genotypes after training. It is suggested
      that hypertrophy of muscle fiber is directly associated with a decrease in
      Myostatin mRNA expression in the C/C genotype, and that increased expressions of
      VEGFa, PGC1alpha, and SDHa in the T/T genotype might be indirectly caused by the
      Myostatin SNP.

PMID- 29058245
TI  - Ocular findings in a patient with oculofaciocardiodental (OFCD) syndrome and a
      novel BCOR pathogenic variant.
AB  - PURPOSE: To report a case of OFCD associated with a de novo BCOR pathogenic
      variant and highlight the ocular findings and possible mechanisms. METHODS: A
      retrospective chart review of the patient's ocular and systemic findings was
      performed. The patient underwent diagnostic whole exome sequencing (WES).
      RESULTS: The patient had a comprehensive eye exam in infancy demonstrating
      bilateral congenital cataracts consisting of posterior lenticonus with a
      posterior cortical opacity. She also had blepharoptosis with a hooded appearance
      and retinal pigment hypertrophy of the inferior retina bilaterally. Systemic
      findings include atrial septal defect, patent ductus arteriosus, congenital
      clubfoot, syndactyly, tethered cord, and laryngeal cleft. WES identified a de
      novo heterozygous R1136X pathogenic variant in the BCOR gene. CONCLUSION: The
      typical ocular manifestation of OFCD syndrome is congenital cataracts, which can
      have a significant impact on visual development and so should be considered in
      patients with multiple medical issues that may fit the diagnosis. A comprehensive
      eye exam in these patients is thus warranted.

PMID- 29058247
TI  - Therapeutic effects of different drugs on obstructive sleep apnea/hypopnea
      syndrome in children.
AB  - BACKGROUND: This study aimed to compare the therapeutic effects of different
      drugs on obstructive sleep apnea/hypopnea syndrome (OSAHS) in children by using a
      network meta-analysis approach. METHODS: PubMed, Embase and Cochrane Library were
      searched from the inception of each database to November 2015. Randomized
      controlled trials (RCTs) concerning the comparisons in the therapeutic effects of
      eight placebo-controlled drugs on OSAHS in children were included in this study.
      Network meta-analysis combined direct evidence and indirect evidence to evaluate
      the weighted mean difference (WMD) and surface under the cumulative ranking
      curves (SUCRA) of therapeutic effects of eight drugs on OSAHS in children.
      RESULTS: A total of seven RCTs were finally incorporated into our network meta
      analysis. Pairwise meta-analysis results revealed that therapeutic effect of
      placebo was significantly poorer than that of intranasal mometasone furoate,
      montelukast, budesonide and fluticasone concerning apnea hypopnea index (AHI)
      value [WMD=1.40, 95% confidence interval (CI)=1.17-1.63; WMD=2.80, 95% CI=1.01
      4.59; WMD=3.50, 95% CI=3.34-3.66; WMD=7.20, 95% CI=5.26-9.14, respectively], and
      fluticasone is better than placebo concerning sleep efficiency (WMD=3.50, 95%
      CI=2.42-4.58); regarding visual analogue scale, the therapeutic effect of placebo
      was poorer compared with sucralfate and clindamycin (WMD=1.94, 95% CI=1.13-2.75;
      WMD=1.06, 95% CI=0.22-1.90), and sucralfate is better than clindamycin (WMD=
      0.88, 95% CI=-1.65 to -0.11). However, network meta-analysis results showed no
      obvious difference in the therapeutic effects of different drugs on OSAHS
      regarding AHI and sleep efficiency. Furthermore, the best SUCRA value was very
      high for fluticasone concerning AHI (86.6%) and budesonide concerning sleep
      efficiency (94.0%) for OSAHS treatment. CONCLUSIONS: Fluticasone and budesonide
      have relatively good effects in the treatment of OSAHS in children, thus
      providing an important guiding significance for the treatment of OSAHS in
      children.

PMID- 29058246
TI  - Factors relating caesarean section to persistent pulmonary hypertension of the
      newborn.
AB  - BACKGROUND: Several studies have clearly demonstrated a significantly higher
      incidence of persistent pulmonary hypertension of the newborn (PPHN) in neonates
      delivered by caesarean section (CS) compared to those delivered vaginally. The
      pathophysiological factors underlying the link between CS and PPHN are still
      poorly understood. In this review, we describe the mechanisms that could explain
      the association between CS delivery and subsequent PPHN, as well as potential
      preventive measures. DATA SOURCES: A literature search was conducted by
      electronic scanning of databases such as PubMed and Web of Science using the key
      words "persistent pulmonary hypertension of the newborn", "caesarean section",
      "iatrogenic prematurity", "oxidative stress", "late preterm", "labor" and
      "vasoactive agents". RESULTS: Iatrogenic prematurity, higher rates of late
      preterm delivery and lack of physiological changes of labor play an important
      role in the association between CS and PPHN. CS delivery also results in limited
      endogenous pulmonary vasodilator synthesis and lower levels of protective anti
      oxidants in the neonates. In addition, CS delivery exposes infants to a higher
      risk of respiratory distress syndrome and its concomitant increase in endothelin
      1 levels, which might indirectly lead to a higher risk of developing PPHN. We
      believe that neonates delivered by CS are exposed to a combination of these
      pathophysiological events, culminating in an endpoint of respiratory distress,
      hypoxia, acidosis, and delayed transition and thereby increased risks of PPHN.
      The use of antenatal corticosteroids prior to elective CS in late preterm
      deliveries, promoting accurate informedconsent process, delaying elective CS to
      39 weeks of gestation or beyond and antenatal maternal anti-oxidant
      supplementation could potentially mitigate the effects of CS delivery and
      minimize CS-related PPHN. CONCLUSIONS: The link between CS delivery and PPHN is
      complex. In view of the rising rates of CS worldwide, there is an urgent need to
      further explore the mechanisms linking CS to PPHN and experimentally test
      therapeutic options in order to allow effective targeted interventions.

PMID- 29058248
TI  - Ventilation during cardiopulmonary resuscitation in children: a survey on
      clinical practice.
AB  - BACKGROUND: This study aimed to investigate the ventilation practice during
      cardiopulmonary resuscitation (CPR) and after return of spontaneous circulation
      (ROSC) in children. METHODS: An online survey of CPR practices was designed and
      sent to healthcare professionals treating children. RESULTS: A total of 477
      healthcare professionals from 46 countries responded to this survey; 92.7% were
      physicians and 64.2% worked in pediatric intensive care units. Specific CPR
      guidelines were used by 97.7% of respondents. The respiratory rate most
      frequently used for children over 12 months was 13 to 20 respirations per minute
      (rpm) (46% in intubated and 41.8% in non-intubated). For infants under 12 months,
      the most frequently used respiratory rate was 21 to 30 rpm in intubated patients
      (37.3%): in non-intubated infants, 13 to 20 rpm (26.5%) and 21 to 30 rpm (26.5%)
      were used with the same frequency. In North America, the respiratory rate most
      widely used was 7 to 12 rpm; higher rates (13 to 20 rpm and 21 to 30 rpm) were
      used in Europe and Latin America (P<0.001). After ROSC, no significant
      differences in the respiratory rates used were found between the continents. More
      than 40% of healthcare professionals had a target oxygen saturation below 94%;
      more than 10% used a target arterial PCO2 below 35 mmHg and more than 13% above
      45 mmHg. CONCLUSIONS: There is considerable variation in the management of
      ventilation of children in cardiac arrest, and international recommendations are
      not being followed in a high percentage of cases.

PMID- 29058249
TI  - A 2-year step-down withdrawal from inhaled corticosteroids in asthmatic children
      receiving immunotherapy.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) for treating asthma are controversial
      because of their negative effects on the growth of asthmatic children and without
      clearly defined withdrawal strategy. A 2-year ICS step-down and withdrawal
      strategy has been developed for asthmatic children receiving 3-year subcutaneous
      immunotherapy (SCIT). METHODS: Eleven children were included into the SCIT group
      and 13 children into the ICS group. ICSs were discontinued when children met the
      following criteria: requiring only 1 puffper day, with good control, for at least
      6 months; having a forced expiratory volume in 1 second (FEV1)/forced vital
      capacity >=80%; and SCIT discontinued for >=24 months. The main endpoints were
      the results of both the childhood asthma control test (C-CAT) and the
      methacholine bronchial provocation test. RESULTS: In the SCIT group, all the 11
      children had ICS discontinued, with one child developed asthma attack after
      pneumonia and received ICS again after completion of SCIT. In the ICS group, five
      children discontinued ICS and developed asthma attacks later and received ICS
      again; the other eight children developed severe symptoms during ICS step-down.
      Thus, the discontinuation of ICS was only achieved in the SCIT group. The dose of
      methacholine that caused a decrease of 20% in FEV1 continued to improve after
      discontinuation of ICS for the SCIT group and presented better results than the
      ICS group (P=0.050). After completion of SCIT, the C-CAT had improved
      significantly after 30 months of treatment compared with the ICS group (P<0.05).
      CONCLUSIONS: In the present study, we developed a 2-year step-down and withdrawal
      strategy from ICSs strategy for allergic asthma children receiving SCIT; the
      strategy was efficacious and safe.

PMID- 29058250
TI  - Trends of childhood diabetes in Southern Thailand: 20-year experience in a
      tertiary medical center.
AB  - BACKGROUND: The incidence and/or prevalence of both childhood diabetes and the
      percent of type 2 diabetes mellitus (T2DM) cases in children and young
      adolescents have been increasing worldwide. This study aimed to examine the 20
      year trends of childhood diabetes in a single tertiary medical center in Southern
      Thailand. METHODS: The medical records of pediatric diabetic patients, aged 0-15
      years, diagnosed at Songklanagarind Hospital from 1995 to 2014 were
      retrospectively reviewed. RESULTS: During the 20-year period, 156 children were
      diagnosed with DM: 99 (63.4%) with T1DM, 43 (27.6%) with T2DM, 2 (1.3%) with
      neonatal diabetes, and 12 (7.7%) with secondary diabetes. The estimated incidence
      of new patients with diabetes per 100 000 per year doubled from 0.12 in 1995
      2000, to 0.24-0.28 in 2001-2004, and further increased to 0.39-0.48 in 2005-2012
      and 0.59-0.64 in 2013-2014; and also the proportion of T2DM cases increased from
      10%-15% during 1995-2003 to 25%-30% during 2004-2008, and 35%-40% during 2009
      2014. At the time of diagnosis, the fasting plasma glucose and glycated
      hemoglobin levels were significantly greater in T1DM than T2DM patients while the
      lipid profiles were more abnormal in T2DM than T1DM patients. CONCLUSIONS: The
      estimated incidences of both T1DM and T2DM in pediatric patients have increased
      markedly over the 20-year period, and also the percentage of T2DM cases, from 10%
      15% in 1995 to 35%-40% in 2014.

PMID- 29058251
TI  - Cutaneous lesions and disorders in healthy neonates and their relationships with
      maternal-neonatal factors: a cross-sectional study.
AB  - BACKGROUND: Cutaneous lesions are very common in neonates. Although a number of
      studies have reported on their incidence, very little is known about the factors
      that influence them. We set out to investigate a large population of neonates
      with the aims of achieving an overall picture of neonatal skin manifestations,
      and examining their relationships with various maternal, neonatal and perinatal
      factors. METHODS: This study was conducted on neonates born at the Department of
      Obstetrics and Gynaecology at the University of Szeged between June 2013 and July
      2015. A total of 4658 consecutive infants underwent a whole-body skin examination
      within the first 72 hours of extrauterine life. The official neonatal medical
      charts were used to collect data on the history of the participating neonates and
      on maternal factors. RESULTS: 74.35% of the neonates exhibited at least one skin
      manifestation. The major diagnosis groups were transient, benign cutaneous
      lesions; vascular lesions; traumatic, iatrogenic, congenital or acquired
      disorders with skin injuries; pigmented lesions; and developmental abnormalities
      or benign skin tumours. The relationships between the skin findings and six
      neonatal or maternal factors were examined: gender, gestational age and birth
      weight of the neonates; maternal age and the number of previous pregnancies of
      the mothers, and mode and circumstances of the delivery. CONCLUSIONS: We found
      several significant correlations between the examined maternal/neonatal factors
      and the occurrence of birthmarks and neonatal skin disorders. Of course, further
      studies are required to confirm and better understand these associations.

PMID- 29058252
TI  - A transversal pilot study of oropharyngeal carriage of Kingella kingae in healthy
      children younger than 6 months.
AB  - BACKGROUND: The aim of this pilot study was to investigate the extent of
      oropharyngeal Kingella kingae carriage during the first 6 months of life.
      METHODS: We conducted a monocentric transversal pilot study on healthy children
      younger than 6 months in order to define the oropharyngeal carriage rate.
      Participants were recruited between December 2013 and September 2015 among
      children without symptoms or signs of invasive infections. RESULTS: We
      demonstrated an oropharyngeal carriage rate of 0.67% in children younger than 6
      months. Due to the really low carriage rate, it was not possible to draw
      statistically significant conclusion about any other characteristic of our
      population. CONCLUSIONS: The present study suggests that the oropharyngeal
      carriage of Kingella kingae among a Swiss population of healthy infants younger
      than 6 months is exceptional. The scarcity of colonization and disease in the
      early months of life suggests thus that defense against mucosal carriage and
      invasive infection is above all provided by vertically acquired immunity. Limited
      exposure of the neonates due to limited social contacts may also represent
      another factor avoiding neonates' mucosal Kingella kingae carriage.

PMID- 29058253
TI  - Why We Still Need To Speak About Sex Differences and Sex Hormones in Pain.
AB  - In the world of pain, we must always consider the presence of gender. In
      nociception, as well as in pain, women are different from men in many, if not
      all, aspects of the system. Nociception is the sum of several events that occur
      from the periphery to the CNS, and there is much evidence that female nociception
      differs from male nociception. Moreover, it has to be considered that pain
      results from a male or a female cortex. Genetic, anatomical, physiological,
      hormonal, psychological, and social factors have been considered to explain the
      differences present at both levels. Notwithstanding all the evidence, it is still
      difficult to observe the application of this knowledge to the treatment of pain.
      Drugs are still given per kilogram, and clinical studies, albeit including women,
      often mix data from both sexes. Moreover, reports on these studies often fail to
      mention the women's age and reproductive status, i.e., sex hormones. Hormone
      levels vary from hour to hour, from day to day, and, as repeatedly confirmed, are
      affected by several pain killers commonly used in pain therapy. All the data
      confirm the urgent need to include sex differences and sex hormones among the key
      factors that play an important role in pain and pain treatment.

PMID- 29058254
TI  - Neuroprotective effects of Ginkgo biloba extract and Ginkgolide B against oxygen
      glucose deprivation/reoxygenation and glucose injury in a new in vitro
      multicellular network model.
AB  - Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is
      characterized by its high incidence, mortality rate, high incurred disability
      rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba
      extract (GBE) against several cerebral diseases have been reported in previous
      studies, but the underlying mechanisms of action are still unclear. Using a novel
      in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model,
      we investigated the neuroprotective effects of GBE and one of its important
      constituents, Ginkgolide B (GB), against oxygen-glucose deprivation/reoxygenation
      and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial
      cells, astrocytes, and neurons were cocultured so that they could be
      synchronously observed in the same system. Pretreatment with GBE or GB increased
      the neuron cell viability, ameliorated cell injury, and inhibited the cell
      apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury.
      Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical
      resistance of capillary endothelial monolayers, reduced the endothelial
      permeability coefficients for sodium fluorescein (Na-F), and increased the
      expression levels of tight junction proteins, namely, ZO-1 and occludin, in
      endothelial cells. Results demonstrated the preventive effects of GBE on neuronal
      cell death and enhancement of the function of brain capillary endothelial
      monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective
      neuroprotective agent for AIS/reperfusion, with GB as one of its significant
      constituents.

PMID- 29058255
TI  - Platelet-rich plasma: combinational treatment modalities for musculoskeletal
      conditions.
AB  - Current research on common musculoskeletal problems, including osteoarticular
      conditions, tendinopathies, and muscle injuries, focuses on regenerative
      translational medicine. Platelet-rich plasma therapies have emerged as a
      potential approach to enhance tissue repair and regeneration. Platelet-rich
      plasma application aims to provide supraphysiological concentrations of platelets
      and optionally leukocytes at injured/pathological tissues mimicking the initial
      stages of healing. However, the efficacy of platelet-rich plasma is controversial
      in chronic diseases because patients' outcomes show partial improvements.
      Platelet-rich plasma can be customized to specific conditions by selecting the
      most appropriate formulation and timing for application or by combining platelet
      rich plasma with synergistic or complementary treatments. To achieve this goal,
      researchers should identify and enhance the main mechanisms of healing. In this
      review, the interactions between platelet-rich plasma and healing mechanisms were
      addressed and research opportunities for customized treatment modalities were
      outlined. The development of combinational platelet-rich plasma treatments that
      can be used safely and effectively to manipulate healing mechanisms would be
      valuable and would provide insights into the processes involved in physiological
      healing and pathological failure.

PMID- 29058256
TI  - Simultaneous detection and characterization of toxigenic Clostridium difficile
      directly from clinical stool specimens.
AB  - We employed a multiplex polymerase chain reaction (PCR) coupled with capillary
      electrophoresis (mPCR-CE) targeting six Clostridium difficile genes, including
      tpi, tcdA, tcdB, cdtA, cdtB, and a deletion in tcdC for simultaneous detection
      and characterization of toxigenic C. difficile directly from fecal specimens. The
      mPCR-CE had a limit of detection of 10 colony-forming units per reaction with no
      cross-reactions with other related bacterial genes. Clinical validation was
      performed on 354 consecutively collected stool specimens from patients with
      suspected C. difficile infection and 45 isolates. The results were compared with
      a reference standard combined with BD MAX Cdiff, real-time cell analysis assay
      (RTCA), and mPCR-CE. The toxigenic C. difficile species were detected in 36
      isolates and 45 stool specimens by the mPCR-CE, which provided a positive rate of
      20.3% (81/399). The mPCR-CE had a specificity of 97.2% and a sensitivity of
      96.0%, which was higher than RTCA (x2 = 5.67, P = 0.017) but lower than BD MAX
      Cdiff (P = 0.245). Among the 45 strains, 44 (97.8%) were determined as
      nonribotype 027 by the mPCR-CE, which was fully agreed with PCR ribotyping. Even
      though ribotypes 017 (n = 8, 17.8%), 001 (n = 6, 13.3%), and 012 (n = 7, 15.6%)
      were predominant in this region, ribotype 027 was an important genotype monitored
      routinely. The mPCR-CE provided an alternative diagnosis tool for the
      simultaneous detection of toxigenic C. difficile in stool and potentially
      differentiated between RT027 and non-RT027.

PMID- 29058257
TI  - Kinetics and pathways of Bezafibrate degradation in UV/chlorine process.
AB  - UV/chlorine, as a novel disinfection method, has attracted great interest due to
      its effective removal for pathogenic microorganism and degradation of trace
      organic contaminants existed in water environment. This paper investigated the
      degradation kinetics and pathways of Bezafibrate (BZF), a typical antilipemic
      drug, during UV/chlorine process. The results showed that 92.3% of BZF was
      degraded after 20 min in UV/chlorine process. This indicated HO* and reactive
      chlorine species (RCSs) formed in UV/chlorine played the dominant role in
      degrading BZF. Observed rate constants of BZF degradation (k obs,BZF) in
      UV/chlorine process increased linearly in a wide chlorine dosage from 0.1 to 1.0
      mM, which implied that ClO* generated from the reactions of chlorine with HO* and
      Cl* could react with BZF rapidly. The steady-state kinetic modeling result proved
      this deduction and the rate constant of ClO* with BZF was fitted to be 5.0 * 108
      M-1 s-1. k obs,BZF was affected by Cl- and HA. The total contribution of RCSs
      (including Cl*, Cl2*-, and ClO*) to the degradation of BZF was determined to be ~
      80%, which is much higher than that of HO*. Thirteen degradation products of BZF
      were identified by LC-MS/MS. Initial degradation products were arisen from
      hydroxylation, chlorine substitution and cyclization by HO* and RCSs, and then
      further oxidized to generate acylamino cleavage and demethylation products.

PMID- 29058258
TI  - Historical accumulation of potentially toxic trace elements resulting from mining
      activities in estuarine salt marshes sediments of the Asturias coastline
      (northern Spain).
AB  - The extensive extraction activity of mercury ores in Asturias (northwest Spain),
      also rich in As and Sb, has impacted the Nalon river estuary. The objective of
      this research was to assess the historical evolution of As-Hg-Sb accumulation in
      the salt marsh sediments of this area. For this purpose, sediment cores were
      collected from two different salt marshes (eastern and western river banks) in
      the estuarine environment to evaluate the degree of anthropogenic enrichment and
      the geochronology of As-Hg-Sb accumulation. Core subsampling was performed by
      cutting 2-cm-thick slices of sediments. The subsamples were then analysed for
      several physical and chemical parameters. Sedimentation rate was assessed by
      measuring short-lived radionuclides (excess 210Pb and 137Cs). Pre-mining levels
      of As-Hg-Sb were observed at core depths below 50 cm. In the less extended salt
      marsh (eastern river bank), maximum As-Hg-Sb concentrations of 87.48, 3.66, and
      5.75 MUg.g-1, respectively, were found at the core top as a consequence of long
      term mining activity in the area. The vertical distribution of As-Hg-Sb was
      influenced by the single-point contamination sources, whereas grain-size
      variability and diagenetic remobilisation did not seem affected. Geochronological
      measurements showed that the depositional fluxes of As-Hg-Sb were influenced by
      anthropogenic input after 1900, when mining activity in the area was most
      intense. Hg mining ceased in 1969; however, the corresponding core profiles did
      not show a drastic decreasing trend in element fluxes, implying that the river
      drainage basin retains some "memory" of contamination which affects riverine
      sediments. A preliminary gross estimation of total As-Hg-Sb "trapped" in the
      Nalon river salt marsh sediments amounted to approximately 18.7, 1.0, and 0.7 t,
      respectively. These morphological structures suffer erosive processes, thus
      representing a potential source of these elements associated with sediments;
      consequently, management conservation and monitoring of salt marshes should be
      taken into consideration from this environmental point of view.

PMID- 29058260
TI  - Progression-Free Survival in Patients Receiving Chemotherapy Alone (C) or
      Chemotherapy with Bevacizumab (CB) for First-Line Treatment of KRAS Mutant
      Metastatic Colorectal Cancer in Community Oncology Settings.
AB  - PURPOSE: Bevacizumab is a standard first-line (L1) treatment for metastatic
      colorectal cancer (mCRC) patients regardless of RAS status. This retrospective
      study examined treatment patterns and outcomes in a community oncology sample of
      KRAS mutant mCRC patients treated with chemotherapy (C) or C plus bevacizumab
      (CB) in L1. METHODS: This study used medical records from the Vector Oncology
      Data Warehouse. Eligible patients were confirmed KRAS mutant mCRC and received L1
      C or CB. Kaplan-Meier analysis assessed L1 progression-free survival (PFS) and
      overall survival (OS). Cox regression models examined the interaction of tumor
      location (R/L) with treatment. RESULTS: CB (n = 264) compared to C (n = 109)
      patients were younger, less likely performance status (PS) impaired, and more
      likely with liver metastases. Median unadjusted PFS was 10.41 months (95% CI 9.0
      11.3) in CB and 7.66 months (95% CI 6.5-9.1) in C patients (p = 0.174). Median
      unadjusted OS was 26.91 months (95% CI 24.3-29.3) in CB and 23.33 months (95% CI
      19.7-29.2) in C patients (p = 0.571). For patients with right- vs. left-sided
      tumors, C (but not CB)-treated patients had higher adjusted risk for progression
      (HR = 1.715, 95% CI 1.108, 2.653; p = 0.015). CONCLUSIONS: CB- vs. C-treated KRAS
      mutant mCRC patients may have a meaningful PFS benefit. Patients with right-sided
      tumors treated with C were at higher risk for disease progression than patients
      with left-sided tumors. Tumor location had no significant effect on outcomes in
      the CB cohort.

PMID- 29058259
TI  - A device-specific prioritization strategy based on the potential for harm to
      human health in informal WEEE recycling.
AB  - In developing countries, the recovery of valuable materials from Waste Electrical
      and Electronic Equipment (WEEE) is carried out via uncontrolled practices, posing
      potentially severe risks both to human health and the environment. The assessment
      of the risk, which depends on both the kind and hazardous properties of the
      substances contained in WEEE, is currently limited as the exposure scenario for
      the single informal practice cannot be fully characterized for this purpose. In
      this context, this work proposes and evaluates a strategy to identify the
      relative potential harm of different kinds of WEEE by their content in metals,
      selected as the target substances of concern. This was based on the individual
      metal content, primarily located in the printed circuit boards (PCBs) of the
      different devices. The metal composition of the individual PCBs was identified
      and the dominant unregulated metal recovery practices were reviewed to identify
      the most suitable parameter to express the toxicity of these metals. Based on a
      mass-normalized cumulative toxicity, via the inhalation route, individual
      components were assessed from compositional variation found in the literature.
      The results is a semiquantitative ranking of individual components, revealing
      significant differences in potential harm posed by different electronic
      appliances and an opportunity to provide prioritization strategies in future
      management.

PMID- 29058261
TI  - Correction to: High expression of HO-1 predicts poor prognosis of ovarian cancer
      patients and promotes proliferation and aggressiveness of ovarian cancer cells.
AB  - n the original version of the article, Table 2 was incorrect. The corrected Table
      2 is shown here. Therefore, in Results (page 3 of original version, right column,
      line 13), the OR of non-optimal debulking should read OR = 3.036 with 95% CI
      1.452-6.348.

PMID- 29058262
TI  - PrediCTC, liquid biopsy in precision oncology: a technology transfer experience
      in the Spanish health system.
AB  - PURPOSE: Management of metastatic disease in oncology includes monitoring of
      therapy response principally by imaging techniques like CT scan. In addition to
      some limitations, the irruption of liquid biopsy and its application in
      personalized medicine has encouraged the development of more efficient
      technologies for prognosis and follow-up of patients in advanced disease.
      METHODS: PrediCTC constitutes a panel of genes for the assessment of circulating
      tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated
      improved efficiency compared to CT scan for the evaluation of early therapy
      response in a multicenter prospective study. In this work, we designed and
      developed a technology transfer strategy to define the market opportunity for an
      eventual implementation of PrediCTC in the clinical practice. RESULTS: This
      included the definition of the regulatory framework, the analysis of the
      regulatory roadmap needed for CE mark, a benchmarking study, the design of a
      product development strategy, a revision of intellectual property, a cost
      effectiveness study and an expert panel consultation. CONCLUSION: The definition
      and analysis of an appropriate technology transfer strategy and the correct
      balance among regulatory, financial and technical determinants are critical for
      the transformation of a promising technology into a viable technology, and for
      the decision of implementing liquid biopsy in the monitoring of therapy response
      in advanced disease.

PMID- 29058265
TI  - Recognizing the 75th anniversary of the Canadian Anesthesiologists' Society: a
      special series of "Images" from our past.

PMID- 29058263
TI  - Ki67 targeted strategies for cancer therapy.
AB  - Ki67 is a well-known proliferation marker for the evaluation of cell
      proliferation. Numerous studies have indicated that Ki67 index independently
      predicts cancer progression. Moreover, because Ki67 is highly expressed in
      malignant cells but almost could not be detected in normal cells, it has become a
      promising target for cancer therapy. In this review, we summarize recent advances
      in Ki67 targeted cancer therapy. In particular, we highlight recent development
      on the exploitation of Ki67 promoter to drive the expression of siRNAs or
      therapeutic genes in cancer cells specifically. The use of Ki67 as an attractive
      target opens a new avenue for cancer therapy.

PMID- 29058264
TI  - SEOM clinical guidelines for anaplastic gliomas (2017).
AB  - The SEOM/GEINO clinical guidelines provide recommendations for radiological, and
      molecular diagnosis, treatment and follow-up of adult patients with anaplastic
      gliomas (AG). We followed the 2016 WHO classification which specifies the major
      diagnostic/prognostic and predictive value of IDH1/IDH2 missense mutations and
      1p/19q codeletions in AG. The diagnosis of anaplastic oligoastrocytoma is
      discouraged. Surgery, radiotherapy and chemotherapy with PCV or TMZ are the first
      line standard of care for AG with slight modifications according to molecular
      variables. A multidisciplinary team is highly recommended in the management of
      these tumors.

PMID- 29058266
TI  - Limitations of pediatric supraglottic airway devices as conduits for intubation -
      an in vitro study.
AB  - PURPOSE: Supraglottic airway devices (SGAs) can be used as conduits for
      intubation, but data and manufacturers' recommendations for pediatric SGA are
      incomplete and sometimes misleading. This situation can result in the use of
      incompatible combinations of SGAs and endotracheal tubes (ETTs). To address this
      mismatch possibility, we performed an in vitro study to establish an overview of
      possible combinations of SGAs and ETTs. METHODS: We tested the passage of ETTs
      through SGAs in vitro and subsequent SGA removal with eight pediatric SGAs and
      six ETTs of different sizes in vitro. Results were compared with manufacturers'
      recommendations. Outcome parameters were the feasibility of passing the ETT
      through the SGA and then removing the SGA over the ETT. RESULTS: The Air-Q(r) and
      the Air-Q(r)spTM SGAs showed the best compatibility with ETTs across all sizes.
      Whenever intubation was possible, removal was possible for all SGAs with uncuffed
      ETTs. With many cuffed ETTs, however, SGA removal was impossible because the ETT
      cuff's pilot balloon was larger than the inner diameter of the SGA. Thus,
      although intubation was possible, removal of the SGA was not. The manufacturers'
      booklets do not warn of this limitation. CONCLUSIONS: The use of combinations of
      SGA and ETTs with a size mismatch can lead to airway complications during
      intubation or to accidental extubation and tearing of the cuff pilot balloon line
      when removing the SGA. To avoid these problems, we devised a table that
      simplifies the choice of an appropriate SGA and ETT combination.

PMID- 29058267
TI  - Robert R. Wilson (1914-2000): the first scientist to propose particle therapy-use
      of particle beam for cancer treatment.

PMID- 29058268
TI  - Early diagnosed cerebrotendinous xanthomatosis patients: clinical,
      neuroradiological characteristics and therapy results of a single center from
      Turkey.
AB  - Cerebrotendinous xanthomatosis (CTX) is a lipid storage disorder caused by
      defective sterol 27-hydroxylase activity. In spite of subtle clinical signs
      beginning from childhood, CTX is generally diagnosed lately. The aim of this
      study is to evaluate clinical, neuroradiological findings and therapy responses
      of pediatric CTX patients and raise awareness to early features of disease.
      Patients who were molecularly diagnosed as CTX before 18 years of age were
      included in study. Clinical, epidemiological, radiological and genotypic features
      of patients and chenodeoxycholic acid (CDCA) therapy responses were reviewed
      retrospectively. Six patients were enrolled in the study. The mean age of
      diagnosis was 11.1 +/- 4.5 years. Apart from previous studies, predominance of
      cerebellar signs over pyramidal signs, peripheral neuropathy with demyelinating
      neuropathy in majority of patients and pathological brain imaging findings
      despite young ages of patients were observed. Intention tremor was the consisting
      finding of all patients. Optic disc drusen was initially reported in one patient.
      Skeletal system involvement as coarse extremities, deformities and early
      osteoporosis was recognized in four patients. CDCA therapy improved or at least
      stabilized neurological functions in all patients. This study is the first CTX
      series from Turkey and performed among only in early diagnosed patients with a
      therapy follow-up contrary to limited data in the literature. We suggest that,
      awareness of intention tremor and ataxic gait in addition to mental retardation,
      peripheral neuropathy and early osteoporosis can be suspicious for CTX and lead
      diagnosis. Early treatment can provide stability and may also ameliorate existing
      neurological findings.

PMID- 29058269
TI  - Muscle strength, functional endurance, and health-related quality of life in
      active older female golfers.
AB  - BACKGROUND: Grip strength is a reliable predictor of whole body strength in older
      adults, but muscle characteristics of people with different activity levels have
      not been studied previously. The present study examined the relationship between
      grip strength (GS), quadriceps peak torque (QPT), functional endurance, and
      health-related quality of life (HRQoL) in older female golfers. METHODS: Twenty
      nine healthy female golfers (mean age 69.1 years, SD 3.4) participated. The
      ISOCOM and JAMAR dynamometers were used to assess QPT and GS, respectively.
      Functional endurance tests included 1-min sit-to-stand test (1MSTS), 30-s wall
      press (30SWP), and 2-min stair climb (2MSC). HRQol was assessed using the SF-36
      questionnaire. RESULTS: Mean GS and QPT were 27.5 +/- 4 kg/f and 103.7 +/- 25.1 N
      m, respectively. Mean scores for the 1MSTS, 30SWP, and 2MSC were 31 +/- 7.7, 17.4
      +/- 3.5, and 237.5 +/- 48.6 repetitions, respectively. GS was moderately
      correlated with QPT (r = 0.44), 1MSTS (r = 0.36), and 2MSC (r = 0.36), but had
      weak correlation with 30SWP (r = 0.003). Moderate correlation was observed
      between quadriceps peak torque and the 1MSTS (r = 0.50; p = 0.01), 2MSC (r =
      0.44; p = 0.02) and 30SWP (r = 0.33). 30SWP and 2MSC had moderate correlations
      with PF r = 0.41 (p = 0.03) and r = 0.61 (p < 0.0005) and general physical well
      being r = 0.47 (p = 0.01) and r = 0.39 (p = 0.04), respectively. CONCLUSION:
      Quadriceps strength was more closely associated with functional endurance than
      grip strength. A single strength measure may not reflect overall muscle
      characteristics in active older females, and hence, assessment of both upper and
      lower limb strengths may be appropriate.

PMID- 29058270
TI  - Double standards in body evaluation? The influence of identification with body
      stimuli on ratings of attractiveness, body fat, and muscle mass.
AB  - Although it is well documented that women evaluate their own body differently
      from other bodies, it remains unclear whether this discrepancy is based on double
      standards because of identity or on objective differences between these bodies.
      The aim of this study was therefore to test whether women apply double standards
      depending on a body's identity when evaluating the same bodies presented with
      different faces. Average-weight women (N = 104) rated body attractiveness, body
      fat, and muscle mass of thin, average-weight, overweight, athletic, and
      hypermuscular bodies with either another female's face or their own face. With
      their own face, subjects rated overweight bodies as more unattractive, higher in
      body fat and lower in muscle mass than with another female's face. However, for
      non-overweight bodies, body ratings did not differ depending on body identity.
      Based on the self-deprecating double standards for overweight bodies, a body
      related identity bias might be considered in theoretical models of body image.
      Level of evidence Level V, descriptive study.

PMID- 29058272
TI  - Personality traits and dysfunctional construal of online health promotion
      messages.
AB  - PURPOSE: With the Internet becoming increasingly popular as a source of
      information, blogs offering healthy lifestyle techniques and knowledge have
      become popular and accessible. Despite their focus on health, these blogs portray
      content that may be negatively construed by viewers, especially those with or at
      risk for eating disorders. The present study investigated changes in affect and
      self-esteem after viewing a prototypic health blog. Personality traits,
      specifically neuroticism and conscientiousness, were also investigated. METHODS:
      A prototypic health blog was constructed after extensive review of existing
      blogs. A parallel format was then followed to create a home decor website for a
      control condition. Female undergraduate students were randomly assigned to one of
      two blog sites, and participants completed an earlier personality assessment and
      post-viewing study questionnaires. RESULTS: Contrary to the hypothesis that
      readers of the health blog will report more negative outcomes, no main effect of
      blog condition was found. However, individuals high in trait neuroticism
      experienced greater differences in negative affect, but not self-esteem, when
      viewing the health blog versus the control blog. CONCLUSIONS: This study found
      that viewing health blogs did not have immediate effects on affect and self
      esteem, but more neurotic individuals were more inclined to experience negative
      affect when viewing health promotion messages. Personality traits assessed prior
      to the experiment were more predictive of negative affect and self-esteem during
      the experiment than blog viewing conditions. No level of evidence, experimental
      study.

PMID- 29058271
TI  - Excessive physical activity in young girls with restrictive-type anorexia
      nervosa: its role on cardiac structure and performance.
AB  - PURPOSE: The aim of this study was to investigate the influence of hyperactivity
      on left ventricular mass (LVM) in Anorexia Nervosa restricting-type (AN-R) and
      the correlation between LVM and auxologic parameters/circulating hormones.
      METHODS: Echocardiography was performed in 44 AN-R girls, subgrouped in 24
      hyperactive (ANH+) and 20 non-hyperactive (ANH-), and in 20 controls (HC). LVM
      indexed to Body Surface Area (LVMi) and LVM indexed to height (LVMh) were
      calculated. RESULTS: LVMi and LVMh were significantly lower in the AN-R subjects
      compared to HC. Moreover, both LVMi and LVMh were higher in the ANH+ than in the
      ANH-. In the HC, LVMi was higher when compared to the ANH- subjects than to the
      ANH+. Stepwise analysis revealed that in the ANH+ group, fT4 was the only
      independent predictor of LVMh, while in the ANH- group, height was the only
      independent predictors of LVMi. CONCLUSIONS: Despite its negative influence on
      disease severity and outcome, hyperactivity from the standpoint of cardiac
      function makes the LVM of AN-R young girls more similar to HC. LEVEL OF EVIDENCE:
      Level III, case-control study.

PMID- 29058273
TI  - How do warmth, safeness and connectedness-related memories and experiences
      explain disordered eating?
AB  - : Literature suggested that the recall of early positive experiences have a major
      impact on the promotion of feelings of connectedness and social safeness, and
      seems to protect individuals against psychopathology. Recent research has also
      demonstrated that the absence of these positive rearing memories play a key role
      on disordered eating-related behaviours. The impact of early affiliative memories
      on disordered eating do not seem to be direct, and the mechanisms underlying this
      relationship are scarcely investigated. The present study aimed to clarify how
      memories of warmth and safeness explain the adoption of disordered eating
      attitudes, and tested the mediator role of social safeness, external shame and
      appearance-focused social comparison on aforementioned relationship, in a sample
      of 277 young women. The tested model explained 36% of eating psychopathology's
      variance and presented an excellent fit. Path analysis results indicated that the
      impact of rearing memories on eating psychopathology was fully mediated through
      the mechanisms of social safeness, external shame and appearance-focused social
      comparison. Specifically, these findings suggested that the extent to which
      positive rearing memories are associated with lower levels of disordered eating
      attitudes is influenced by the current feelings of social safeness and
      connectedness, which in turn are totally carried by decreased feelings of
      external shame and by lower endorsement on unfavourable comparison based on
      physical appearance with proximal targets (peers). These results seem to offer
      important insights for research and clinical work on body image and eating
      related difficulties, suggesting the relevance of promoting warm and safe
      interactions with others. LEVEL OF EVIDENCE: Level V, descriptive study.

PMID- 29058274
TI  - Carbon nanotubes-based drug delivery to cancer and brain.
AB  - Current treatments for cancer and the central nervous system diseases are
      limited, partly due to the difficulties posed by the insolubility, poor
      distribution of drugs among cells and lack of selectivity of drugs, the inability
      of drugs to cross cellular barriers and blood brain barrier (BBB). Carbon
      nanotubes (CNTs) possess many distinct properties including good electronic
      properties, remarkably penetrating capability on the cell membrane, high drug
      loading and pH-dependent therapeutic unloading capacities, thermal properties,
      large surface area and easy modification with molecules, which render them as a
      suitable candidate to deliver drugs to cancer and brain. CNTs as a drug delivery
      could achieve a high efficacy, enhance specificity and diminish side effects.
      Whereas CNTs have been primarily employed in cancer treatment, a few studies have
      focused on the treatment and diagnosis of the central nervous system diseases
      using CNTs. Here, we review the current progress of in vitro and in vivo
      researches of CNTs-based drug delivery to cancer involving CNTs-based tumor
      targeted drug delivery systems (DDS), photodynamic therapy (PDT) and photothermal
      therapy (PTT). Meanwhile, we also review the current progress of in vitro and in
      vivo researches of CNTs-based drug delivery to brain.

PMID- 29058275
TI  - Effect of recurrent severe hypoglycemia on cognitive performance in adult
      patients with diabetes: A meta-analysis.
AB  - The purpose of this study was to investigate the existence and extent of
      cognitive impairment in adult diabetes mellitus (DM) patients with episodes of
      recurrent severe hypoglycemia, by using meta-analysis to synthesize data across
      studies. PubMed, EMBASE and Cochrane library search engines were used to identify
      studies on cognitive performance in DM patients with recurrent severe
      hypoglycemia. Random-effects meta-analysis was performed on seven eligible
      studies using an inverse-variance method. Effect sizes, which are the
      standardized differences between the experimental group and the control group,
      were calculated. Of the 853 studies, 7 studies met the inclusion criteria.
      Compared with control subjects, the adult DM patients with episodes of recurrent
      severe hypoglycemia demonstrated a significantly lowered performance on memory in
      both types of DM patients, and poor performance of processing speed in type 2 DM
      patients. There was no significant difference between adult DM patients with and
      those without severe hypoglycemia in other cognitive domains such as general
      intelligence, executive function, processing speed and psychomotor efficiency.
      Our results seem to confirm the hypothesis that cognitive dysfunction is
      characterized by worse memory and processing speed in adult DM patients with a
      history of recurrent severe hypoglycemia, whereas general intelligence, executive
      function, and psychomotor efficiency are spared.

PMID- 29058276
TI  - Comparison of diagnosing and staging accuracy of PET (CT) and MIBG on patients
      with neuroblastoma: Systemic review and meta-analysis.
AB  - To perform a systemic review and meta-analysis of the diagnostic accuracy of PET
      (CT) and metaiodobenzylguanidine (MIBG) for diagnosing neuroblastoma (NB),
      electronic databases were searched as well as relevant references and conference
      proceedings. The diagnostic accuracy of MIBG and PET (CT) was calculated for NB,
      primary NB, and relapse/metastasis of NB based on their sensitivity, specificity,
      and area under the summary receiver operating characteristic curve (AUSROC) in
      terms of per-lesion and per-patient data. A total of 40 eligible studies
      comprising 1134 patients with 939 NB lesions were considered for the meta
      analysis. For the staging of NB, the per-lesion AUSROC value of MIBG was lower
      than that of PET (CT) [0.8064+/-0.0414 vs. 0.9366+/-0.0166 (P<0.05)]. The per
      patient AUSROC value of MIBG and PET (CT) for the diagnosis of NB was 0.8771+/
      0.0230 and 0.6851+/-0.2111, respectively. The summary sensitivity for MIBG and
      PET (CT) was 0.79 and 0.89, respectively. The summary specificity for MIBG and
      PET (CT) was 0.84 and 0.71, respectively. PET (CT) showed higher per-lesion
      accuracy than MIBG and might be the preferred modality for the staging of NB. On
      the other hand, MIBG has a comparable diagnosing performance with PET (CT) in per
      patient analysis but shows a better specificity.

PMID- 29058278
TI  - Cable pin system versus K-wire tension band fixation for patella fractures in
      Chinese Han population: A meta-analysis.
AB  - This meta-analysis compared the therapeutic effect of cable pin system (CPS) with
      K-wire tension band (KTB) in the treatment of patella fractures among Chinese Han
      population. The databases of PubMed, Cochrane library, China National Knowledge
      Infrastructure (CNKI), Chinese WanFang and Chinese VIP were searched for studies
      on CPS versus KTB in the treatment of patella fractures among Chinese Han
      population. Literatures were screened according to the inclusion and exclusion
      criteria. The quality of the studies was assessed, and meta-analysis was
      performed using the Cochrane Collaboration's REVMAN 5.3 software. A total of 932
      patients from 15 studies were included in this meta-analysis (426 fractures
      treated with CPS and 506 fractures treated with KTB). There were significant
      differences in duration of hospital stay [mean difference (MD)=-1.07; 95%
      confidence interval (CI):-1.71 to-0.43], fracture healing time (MD=-1.23; 95% CI:
      1.68 to-0.77), flexion degree of knee joint at 6th month after operation
      (MD=14.82; 95% CI: 10.93 to 18.71), incidence of postoperative complication [risk
      ratio (RR)=0.16; 95% CI: 0.09 to 0.27] and excellent-good rate of Bostman score
      (RR=1.09; 95% CI: 1.03 to 1.16) between the CPS group and KTB group, while no
      significant difference was found in operative time between the two groups (MD=
      4.52; 95% CI:-11.70 to 2.67). For the treatment of patella fractures among
      Chinese Han population, limited evidence suggests that the CPS is more suitable
      than the KTB when considering the hospital stay, fracture healing time, flexion
      degree of knee at 6th month after operation, incidence of postoperative
      complication and excellent-good rate of Bostman joint score. Due to the
      limitation of high quality evidence and sample size, more large-scale randomized
      controlled trials are needed to validate the findings in the future.

PMID- 29058277
TI  - Relationship between expression of vascular endothelial growth factor and
      cervical lymph node metastasis in papillary thyroid cancer: A meta-analysis.
AB  - The aim of the present study was to examine the relationship between the protein
      expression of vascular endothelial growth factor (VEGF) and lymph node metastasis
      (LNM) in papillary thyroid cancer (PTC). VEGF-related articles that had been
      published until August 2016 were searched from the PubMed, EMBASE, and MEDLINE to
      identify the risk factors of LNM in PTC. RevMan 5.3 software was used for the
      meta-analysis. Finally, 9 articles met the inclusion criteria and were included
      in our meta-analysis. LNM was found to be present in 176 of 318 patients (57.8%)
      with high VEGF expression and in 71 of 159 patients (47.0%) with low VEGF
      expression. The overall OR was 2.81 (95% confidence interval, 1.49-5.29). LNM
      occurred more frequently in patients with high VEGF expression than in those with
      low VEGF expression (P=0.001). Heterogeneity was markedly decreased in the
      subgroup analyses of LNM in terms of the patients' country of origin and the
      detection methods. Our meta- analysis concluded that the VEGF protein expression
      is associated with LNM in PTC.

PMID- 29058279
TI  - Comparison of treatment outcomes of ticagrelor and clopidogrel among patients
      undergoing percutaneous coronary intervention: A meta-analysis.
AB  - We performed a meta-analysis of randomized controlled trials (RCTs) to
      investigate the efficacy and safety of ticagrelor (TIC) vs. clopidogrel (CLO) in
      patients undergoing percutaneous coronary intervention (PCI). In Jun 2016, a
      literature search was started and all the studies were conducted from 2010 to
      2015. We systematically searched the literature through the MEDLINE database,
      Cochrane library, and EMBASE database. Quality assessments were evaluated with
      Jadad quality scale. Data were extracted considering the characteristics of
      efficacy and safety designs. Six RCTs enrolling 26 244 participants and
      satisfying the inclusion criteria were finally analyzed. There was a significant
      decrease of all-cause mortality (MD=0.83, 95%CI=0.74-0.93, P=0.001) and
      myocardial infarction (MI) (MD=0.78, 95%CI=0.70-0.88, P=0.000). There were no
      significant differences in stroke (MD=1.34, 95%CI=0.99-1.79, P=0.06), total
      bleeding (MD=0.97, 95%CI=0.84-1.12, P=0.66), minor or major bleeding (MD=1.06,
      95%CI=0.94-1.19, P=0.35) in patients undergoing PCI after treatment with TIC vs.
      CLO. TIC could be more significant in decreasing all-cause mortality and MI than
      CLO, but there were no significant differences between TIC and CLO in inhibiting
      stroke, major bleeding, major or minor bleeding in patients undergoing PCI.

PMID- 29058280
TI  - Bootstrapping data envelopment analysis of efficiency and productivity of county
      public hospitals in Eastern, Central, and Western China after the public hospital
      reform.
AB  - China implemented the public hospital reform in 2012. This study utilized
      bootstrapping data envelopment analysis (DEA) to evaluate the technical
      efficiency (TE) and productivity of county public hospitals in Eastern, Central,
      and Western China after the 2012 public hospital reform. Data from 127 county
      public hospitals (39, 45, and 43 in Eastern, Central, and Western China,
      respectively) were collected during 2012-2015. Changes of TE and productivity
      over time were estimated by bootstrapping DEA and bootstrapping Malmquist. The
      disparities in TE and productivity among public hospitals in the three regions of
      China were compared by Kruskal-Wallis H test and Mann-Whitney U test. The average
      bias-corrected TE values for the four-year period were 0.6442, 0.5785, 0.6099,
      and 0.6094 in Eastern, Central, and Western China, and the entire country
      respectively, with average non-technical efficiency, low pure technical
      efficiency (PTE), and high scale efficiency found. Productivity increased by
      8.12%, 0.25%, 12.11%, and 11.58% in China and its three regions during 2012-2015,
      and such increase in productivity resulted from progressive technological changes
      by 16.42%, 6.32%, 21.08%, and 21.42%, respectively. The TE and PTE of the county
      hospitals significantly differed among the three regions of China. Eastern and
      Western China showed significantly higher TE and PTE than Central China. More
      than 60% of county public hospitals in China and its three areas operated at
      decreasing return scales. There was a considerable space for TE improvement in
      county hospitals in China and its three regions. During 2012-2015, the hospitals
      experienced progressive productivity; however, the PTE changed adversely.
      Moreover, Central China continuously achieved a significantly lower efficiency
      score than Eastern and Western China. Decision makers and administrators in China
      should identify the causes of the observed inefficiencies and take appropriate
      measures to increase the efficiency of county public hospitals in the three areas
      of China, especially in Central China.

PMID- 29058281
TI  - Decitabine for relapsed acute lymphoblastic leukemia after allogeneic
      hematopoietic stem cell transplantation.
AB  - Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT)
      remains a main question on treatment failure. Current strategies for management
      that usually include salvage chemotherapy, donor lymphocytic infusion and second
      transplantation. Our study assessed the efficacy of decitabine (DAC) for treating
      patients with acute lymphoblastic leukemia (ALL) who relapsed after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed
      the outcomes of 12 patients with relapsed ALL after allo-HSCT who received DAC
      therapy. Nine patients received DAC combined with chemotherapy and donor stem
      cell infusion, and 3 patients received single- agent DAC. Ten of the 12 patients
      achieved complete remission (CR), 1 achieved a partial remission (PR), and 1 had
      no response (NR) after treatment at the latest follow-up (LFU), the median
      survival was 11.2 months (range, 3.8-34, 7 months). The 1- and 2-year overall
      survival (OS) rates were 50% (6/12) and 25% (3/12), respectively. Five patients
      were still alive; 4 had maintained CR and 1 was alive with disease. Patients with
      Philadelphia chromosome-positive ALL had higher survival rate than patients with
      Philadelphia chromosome-negative ALL (57.1% vs. 20%). No aggravated flares of
      graft-versus-host disease (GVHD) were observed during DAC treatment. Therefore,
      DAC may be a promising therapeutic agent for ALL recurrence after allo-HSCT.

PMID- 29058282
TI  - Roles of TGF-beta signaling pathway in endoplasmic reticulum stress in
      endothelial cells stimulated with cigarette smoke extract.
AB  - To investigate the role of signaling pathway in the effect of endoplasmic
      reticulum stress (ER stress) in endothelial cells stimulated with cigarette smoke
      extract (CSE). Human umbilical vein endothelial cells (HUVECs) were cultured and
      divided into 3 groups: CSE-stimulated group, CSE-stimulated with 4-PBA group, and
      negative control group. HUVECs were cultured and stimulated with CSE at
      concentrations of 5%, 10% and 20%, respectively, mRNA of CXCL-8 and GRP78 was
      detected by real-time PCR. ELISA was performed to test the expression of CXCL-8
      protein, and neutrophils migration was detected by Transwell board test. The NF
      kappaB, ERK, p38MAPK and transforming growth factor beta (TGF-beta) were detected
      by flow cytometry. The mRNA of CXCL-8 and GRP78 increased in CSE-stimulated
      HUVECs (P<0.05). Furthermore, it was concentration-dependent. 4-PBA significantly
      reduced the expression of CXCL-8 protein (P<0.05) and neutrophil migration
      (P<0.05). The TGF-beta, rather than the NF-kappaB, ERK and P38MAPK pathway might
      be involved in ER stress stimulated by CSE. CSE induced neutrophils migration by
      increasing the expression of CXCL-8 in endothelial cells. ER stress might play a
      role in the effect of neutrophils migration stimulated with CSE, and TGF-beta
      pathway may contribute to the ER stress in HUVECs.

PMID- 29058283
TI  - Changes in hydrogen sulfide in rats with hepatic cirrhosis in different stages.
AB  - This study aimed to observe changes in the hydrogen sulfide (H2S) system in the
      blood and liver tissue of rats with hepatic cirrhosis at different stages by
      studying the effect of H2S on the course of hyperdynamic circulation in rats with
      hepatic cirrhosis. H2S concentration in the blood from the portal vein and
      inferior vena cava of hepatic cirrhosis rat model induced with carbon
      tetrachloride was detected on the 15th, 30th, and 52nd day. The expression of
      cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) protein,
      and CBS and CSE mRNA in the liver was detected by immunohistochemistry and
      reverse transcriptase polymerase chain reaction (RT-PCR), respectively. The
      results indicated that H2S concentration in the blood from the portal vein and
      inferior vena cava of rats with hepatic cirrhosis was significantly lower than
      that in the control group. H2S was gradually decreased with the development of
      the disease and significantly lower in the blood from portal vein than in the
      blood of inferior vena cava at the mid-stage and the late stage groups. The
      expression levels of CBS and CSE protein, and CBS and CSE mRNA in the livers with
      hepatic cirrhosis at different stages were all higher than those in the control
      group, and the expression gradually increased with the development of the
      disease. The expression of CBS was lower than CSE in the same stages. The results
      indicated that the CSE mRNA was expressed predominantly in the cirrhosis groups
      as compared with CBS mRNA. Among experimental rats, the H2S system has an
      important effect on the occurrence and development of hyperdynamic circulation in
      rats with hepatic cirrhosis. This finding adds to the literature by demonstrating
      that H2S protects vascular remodelling in the liver, and that CSE is
      indispensable in this process.

PMID- 29058284
TI  - Glycemic index, glycemic load, and glycemic response to pomelo in patients with
      type 2 diabetes.
AB  - Food intake has a great influence on blood glucose in patients with diabetes.
      This study was to determine the glycemic index (GI) and glycemic load (GL) of a
      particular pomelo named Majia pomelo and its effects on postprandial glucose
      (PPG) in patients with type 2 diabetes (T2D). Twenty healthy subjects and 20 T2D
      patients (controlled on lifestyle measures and/or metformin) were tested on 2
      separate days with 50 g of glucose and 50 g equivalent of carbohydrates from
      Majia pomelo for GI measurement. To test effects of Majia pomelo on PPG, 19
      hospitalized T2D patients (controlled on insulin therapy) were selected for a 9
      day study. The dose of insulin for each patient was adjusted on the first 3 days.
      A total of 100 mg Majia pomelo was consumed per meal in the last 3 tested days.
      Blood glucose was measured to evaluate the glycemic excursions. The GIs for Majia
      pomelo in healthy individuals and T2D patients were 78.34+/-1.88 and 72.15+/-1.95
      respectively. The value of GL was as low as 4.23 in diabetic patients with
      serving size of 100 g pomelo, indicting Majia pomelo as a high GI but low GL
      fruit. Consumption of Majia pomelo in hospitalized T2D patients did not cause
      significant glucose fluctuation. It was concluded that high GI pomelo can serve
      as a low GL fruit if it is consumed with a limited daily amount and thus can be
      supplied to diabetic patients. These results may mean more varieties of food
      choices for T2D patients.

PMID- 29058285
TI  - Notch4 inhibition suppresses invasion and vasculogenic mimicry formation of
      hepatocellular carcinoma cells.
AB  - Vasculogenic mimicry (VM) is a process by which aggressive tumor cells generate
      non-endothelial cell-lined channels in malignant tumors including hepatocellular
      carcinoma (HCC). It has provided new insights into tumor behavior and has
      surfaced as a potential target for drug therapy. The molecular events underlying
      the process of VM formation are still poorly understood. In this study, we
      attempted to elucidate the relationship between Notch4 and VM formation in HCC.
      An effective siRNA lentiviral vector targeting Notch4 was constructed and
      transfected into Bel7402, a HCC cell line. VM networks were observed with a
      microscope in a 3 dimensional cell culture system. Cell migration and invasion
      were evaluated using wound healing and transwell assays. Matrix
      metalloproteinases (MMPs) activity was detected by gelatin zymography.
      Furthermore, the role of Notch4 inhibition in Bel7402 cells in vivo was examined
      in subcutaneous xenograft tumor model of mice. The results showed that
      downregulation of Notch4 destroyed VM network formation and inhibited migration
      and invasion of tumor cells in vitro (P<0.05). In vivo, tumor growth was also
      inhibited in subcutaneous xenograft model (P<0.05). The potential mechanisms
      might be related with down-regulation of MT1-MMP, MMP-2, MMP-9 expression and
      inhibition of the activation of MMP2 and MMP9. These results indicated that
      Notch4 may play an important role in VM formation and tumor invasion in HCC.
      Related molecular pathways may be used as novel therapeutic targets for HCC
      antiangiogenesis therapy.

PMID- 29058286
TI  - Treatment of retrogastric pancreatic pseudocysts by laparoscopic transgastric
      cystogastrostomy.
AB  - This paper discusses variations of laparoscopic transgastric cystogastrostomy in
      management of retrogastric pancreatic pseudocysts for 8 patients with symptom or
      pseudocysts (larger than 6 cm) companied with clinical manifestations. Using a
      Harmonic scalpel, two 3-5-cm incisions were made in the anterior and posterior
      gastric wall respectively. In the last step, the anterior gastrotomy was closed
      with an Endo-GIA stapler. All cases were successfully treated without large blood
      loss and without conversion to open surgery. The mean operative time was 114.29+/
      19.24 min, blood loss was 157.14+/-78.70 mL, and mean hospital stay was 8.29+/
      2.98 days. Gastric fistula occurred in one case on the postoperative day 7, and
      closed 1 month later. No bleeding was seen in all patients during the
      perioperative follow-up period. CT scans, given one month after the surgeries,
      displayed that the pancreatic pseudocysts disappeared or decreased in size, and
      ultrasounds showed no fluid or food residue in stomas at the third and fifth
      month following surgery. No patient experienced a recurrence during the follow-up
      period. Transgastric laparoscopic cystogastrostomy is a minimally invasive
      surgical procedure with a high rate of success and a low rate of recurrence,
      accompanied by rapid recovery. It is easy to master, safe to perform and may be
      the preferred option to treat retrogastric pancreatic pseudocysts.

PMID- 29058287
TI  - Aberrant activation of Cdc2/cyclin B1 is involved in initiation of cytoskeletal
      pathology in murine Niemann-Pick disease type C.
AB  - Niemann-Pick disease type C (NPC) is a fatal, neurovisceral lipid storage
      disease, neuropathologically characterized by cytoplasmic sequestration of
      glycolipids in neurons, progressive neuronal loss, neurofibrillary tangles (NFTs)
      formation, and axonal spheroids (AS). Cytoskeletal pathology including
      accumulation of hyperphosphorylated cytoskeletal proteins is a neuropathological
      hallmark of the mouse model of NPC (npc mice). With a goal of elucidating the
      mechanisms underlying the lesion formation, we investigated the temporal and
      spatial characteristics of cytoskeletal lesions and the roles of cdc2, cdk4, and
      cdk5 in lesion formation in young npc mice. Cytoskeletal lesions were detectable
      in npc mice at three weeks of age. Importantly, concomitant activation of
      cdc2/cyclin B1 kinase and accumulation of a subsequently generated cohort of
      phospho-epitopes were detected. The activation of cdk4/cyclin D1 and cdk5/p25
      kinases was observed during the fourth week of life in npc mice, and this
      activation contributed to the lesion formation. We concluded that the progression
      of cytoskeletal pathology in npc mice older than four weeks is accelerated by the
      cumulative effect of cdc2, cdk4, and cdk5 activation. Furthermore, cdc2/cyclin B1
      may act as a key initial player one week earlier. Targeting cell cycle activation
      may be beneficial to slow down the NPC pathogenesis.

PMID- 29058288
TI  - Correlation between UGT1A1 polymorphism and neonatal hyperbilirubinemia of
      neonates in Wuhan.
AB  - This study attempts to discuss the correlation between UGT1A1*28 as uridine
      diphosphate glucuronosyltransferase gene promoter and coding region Gly71Arg gene
      polymorphism with neonatal hyperbilirubinemia of neonates in Wuhan. A total of
      168 neonates were divided into the hyperbilirubinemia group (case group, n=108)
      and healthy neonates group (control group, n=60). Their DNA was obtained through
      blood extraction. The gene exon mutation of UGT1A1 was detected by Sanger
      sequencing, which revealed the relationship between UGT1A1*28 and Gly71Arg
      polymorphism with neonatal hyperbilirubinemia of neonates. The results showed
      that: (1) The frequency of UGT1A1*28 allele mutation in the case group and the
      control group was 9.3% and 10% respectively, with the difference being not
      significant between the two groups (P>0.05). (2) The frequency of Gly71Arg allele
      mutation in the case group and the control group was 35.1% and 21.7%
      respectively, with the difference being significant between the two groups
      (P<0.01). (3) The serum bilirubin level of Gly71Arg mutant homozygous and
      heterozygous subgroups (n=66) in the case group was 302.7+/-31.4 MUmol/L, which
      was significantly higher than 267.3+/-28.5 MUmol/L of the wild subgroup (n=42)
      (P<0.01). It was suggested that the occurrence of neonatal hyperbilirubinemia of
      neonates in Wuhan was not associated with UGT1A1*28 gene polymorphism, but
      closely with the Gly71Arg gene polymorphism. Meanwhile, the Arg allele mutation
      was related to the degree of jaundice.

PMID- 29058289
TI  - Down-regulation of NOX4 by betulinic acid protects against cerebral ischemia
      reperfusion in mice.
AB  - Ischemic stroke leads to high potentiality of mortality and disability. The
      current treatment for ischemic stroke is mainly focused on intravenous
      thrombolytic therapy. However, ischemia/ reperfusion induces neuronal damage,
      which significantly influences the outcome of patients with ischemic stroke, and
      the exact mechanism implicated in ischemia/reperfusion injury remains unclear,
      although evidence shows that oxidative stress is likely to be involved. Betulinic
      acid is mainly known for its anti-tumor and anti-inflammatory activities. Our
      previous study showed that betulinic acid could decrease the reactive oxygen
      species (ROS) production by regulating the expression of NADPH oxidase. Thus, we
      hypothesized that betulinic acid may protect against brain ischemic injury in the
      animal model of stroke. Focal cerebral ischemia was achieved by using the
      standard intraluminal occlusion method and reperfusion enabled after 2 h
      ischemia. Neurological deficits were scored. Infarct size was determined with
      2,3,5-triphenyltetrazolium chloride monohydrate (TTC) staining and the mRNA
      expression of NADPH oxidase 4 (NOX4) was determined by RT-PCR in infarct tissue.
      ROS generation and apoptosis in ischemic tissue were analyzed by measuring the
      oxidative conversion of cell permeable 2',7'-dichloro-fluorescein diacetate (DCF
      DA) to fluorescent dichlorofluorescein (DCF) in fluorescence microplate reader
      and TUNEL assay, respectively. In Kunming mice, 2 h of middle cerebral artery
      (MCA) occlusion followed by 24 or 72 h of reperfusion led to an enhanced NOX4
      expression in the ischemic hemisphere. This was associated with elevated levels
      of ROS generation and neuronal apoptosis. Pre-treatment with betulinic acid (50
      mg/kg/day for 7 days via gavage) prior to MCA occlusion prevented the
      ischemia/reperfusion-induced up-regulation of NOX4 and ROS production. In
      addition, treatment with betulinic acid could markedly blunt the
      ischemia/reperfusion-induced neuronal apoptosis. Finally, betulinic acid reduced
      infarct volume and ameliorated the neurological deficit in this stroke mouse
      model. Our results suggest that betulinic acid protects against cerebral
      ischemia/reperfusion injury in mice and the down-regulation of NOX4 may represent
      a mechanism contributing to this effect.

PMID- 29058290
TI  - Mental health status assessment in polycystic ovarian syndrome infertility
      patients: A pilot study.
AB  - Polycystic ovary syndrome (PCOS) is a major endocrine disorder afflicting women
      of reproductive age. Women with PCOS are more likely to suffer from mental health
      disturbances than healthy women. The "infertility" suffered by PCOS patients
      would also lead to mental health disturbances. Symptom Checklist 90 (SCL-90) and
      questionnaire which includes patients' socio-economic and demographic data were
      used to assess the mental health status of PCOS (n=103) and non-PCOS (n=110)
      infertile patients. Logistic regression analysis and t-tests were used for
      comparative analysis. The data demonstrated that scores of depression,
      interpersonal sensitivity, obsessive-compulsive, and hostility symptoms in PCOS
      infertile patients were significantly higher than those in the non-PCOS infertile
      patients (P<0.05). Logistic regression analysis revealed that acne had negative
      effect on mental health status (P<0.05). Secondary infertile PCOS patients were
      more easily to suffer from somatization, interpersonal sensitivity, obsessive
      compulsive, anxiety, hostility and paranoid ideation symptoms than the primary
      infertile PCOS patients (P<0.05). The results suggested that the PCOS patients
      especially the secondary infertile PCOS patients had obvious mental health
      disturbances. The acne might play an importance role in the occurrence of mental
      health disturbances in PCOS patients. PCOS related symptoms may be risk factors
      of mental health status in PCOS patients with infertility. More attention should
      be paid to the PCOS infertile patients, and mental health therapy should be
      considered if necessary.

PMID- 29058291
TI  - Association of mRNA expression level of IP-10 in peripheral blood mononuclear
      cells with HBV-associated acute-on-chronic liver failure and its prognosis.
AB  - HBV-associated acute-on-chronic liver failure is prevalent in mainland China. The
      prognosis of HBV-ACLF is poor. The mortality of HBV-ACLF is approximately 80%.
      Therefore, a prognostic indicator was needed in order to allow us to intervene as
      soon as possible. The model for end-stage liver disease (MELD) scoring system is
      widely used to predict the prognosis of liver failure. However, the assessment is
      too complex to restrict its application. This study aimed to investigate the
      expression of IP-10 in peripheral blood mononuclear cells (PBMC), in order to
      explore the relationship between the expression and prognosis of patients with
      HBV-ACLF. The mRNA level of IP-10 in PBMCs were analyzed in 80 patients with HBV
      ACLF, 40 patients with chronic hepatitis B (CHB) and 40 healthy people by
      fluorescent quantitative PCR. IP-10 mRNA level was significantly higher in the
      HBV-ACLF group than in the other two groups (P<0.01). Group with MELD score below
      30 had lower IP-10 mRNA level than group with MELD score over 30 (P<0.05). The IP
      10 mRNA level in PBMCs in positive group was higher than that in negative group
      (P<0.01). With a threshold of 0.925, the area under the receiver operating
      characteristic (ROC) curves was 0.815. These findings suggest that assessment of
      IP-10 mRNA level in the PBMCs would be helpful for evaluating the disease
      severity and prognosis in patients with HBV-ACLF.

PMID- 29058293
TI  - Chinese medicine formula "Shenqi San" extract inhibits proliferation of human
      lung adenocarcinoma A549 cells via inducing apoptosis.
AB  - The main purpose of this study was to investigate the active components of the
      Chinese medicine formula Shenqi San (SS) by high performance liquid
      chromatography with diode array detector and electrospray ionization-hybrid
      quadrupole time-of-flight mass spectrum (HPLC-DADESI- QTOF-MS), and demonstrate
      the anticancer mechanism of SS on human lung adenocarcinoma A549 cells by
      evaluating the cell proliferation and apoptosis induction. The chloroform
      extraction of SS (CE-SS) was extracted from SS, while HPLC-DAD-ESI-QTOF-MS assay
      was performed to identify components of CE-SS. MTT assay was used to quantify the
      proliferation of A549 cells with the treatment of CE-SS. Apoptosis analysis was
      carried out by detecting phosphatidylserine (PS) externalization using the
      Annexin V-FITC Apoptosis Detection Kit and the stained cells were analyzed with a
      flow cytometer. DAPI staining assay was carried out to observe morphological
      characteristics of apoptotic cells. Western blotting was used to detect the
      expression of important signaling proteins including caspase-3, -8, -9, p53, Bax
      and Bcl-2. Eight compounds were identified through HPLC-DAD-ESI-QTOF-MS analysis
      and 3-pyridine carboxylic acid, barbatin C, scutebarbatine F and barbatine D
      might be the main compounds responsible for the antitumor effect of CE-SS. CE-SS
      suppressed the proliferation of lung cancer A549 cells in a time- and dose
      dependent manner. By Annexin V-FITC/PI double staining, we found that treatment
      with CE-SS induced apoptosis in A549 cells. After 24-h exposure to CE-SS, the
      expression of cleaved-caspase-9, cleaved-caspase-8 and cleaved-caspase-3 protein
      was activated, the expression of p53 protein increased while the ratio of Bax/Bcl
      2 also increased. This study identified the eight compounds of CE-SS, and
      demonstrated their anticancer effect on human lung adenocarcinoma A549 cells via
      induction of apoptosis.

PMID- 29058292
TI  - Danshen modulates Nrf2-mediated signaling pathway in cisplatin-induced renal
      injury.
AB  - Danshen, an efficacious agent for cardiovascular diseases, has been found to play
      an essential role in kidney injury. In the present study, the effect of Danshen
      on cisplatin-induced renal dysfunction was investigated in a mouse model. Danshen
      was administered to mice at a dose of 3 g/kg 4 days before and 3 days after
      cisplatin treatment. A single intraperitoneal injection of 20 mg/kg cisplatin was
      used to induce nephrotoxicity. The mice were sacrificed 72 h after cisplatin
      intoxication. Biochemical parameters including serum creatinine and blood urea
      nitrogen were analyzed. Histopathological changes of kidney tissues were detected
      using HE staining. Antioxidant enzymes (GSH-Px and SOD) and peroxidative product
      (MDA) were detected. Protein expressions of Nrf2 and its target genes including
      HO-1 and NQO1 were measured by Western blotting. The results showed that
      pretreatment with Danshen significantly reduced serum creatinine and blood urea
      nitrogen in the cisplatin-treated mice. Histopathological examination showed that
      Danshen mitigated the renal damage induced by cisplatin. Moreover, Danshen
      restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized
      the MDA contents in renal tissues. Western blotting revealed that Danshen
      enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice.
      It was suggested that Danshen protects against the cisplatin-induced renal
      impairment in the mice, which is potentially associated with the upregulation of
      Nrf2-mediated signaling pathway.

PMID- 29058294
TI  - A novel gene mutation of Runx2 in cleidocranial dysplasia.
AB  - Haploinsufficiency of the runt-related transcription factor 2 (Runx2) gene is
      widely known to be responsible for cleidocranial dysplasia (CCD). To date, more
      than 190 mutations in Runx2 gene have been reported to be related to CCD. In this
      study, a novel mutation of Runx2 gene was observed in a female with CCD. Genomic
      DNA was extracted from peripheral venous blood of the proband and eleven members
      of her family. Genetic testing on these twelve people identified a novel missense
      mutation (c.895 T>C, Y299H) in exon 5 of the RUNX2 gene in the proband. This
      mutation results in an amino acid change at codon 895 (P.Tyr 299 His.) from a
      tryptophan codon (TAT) to a histidine codon (CAT). Our finding may further extend
      the known mutation spectrum of the RUNX2 gene, and facilitate prenatal genetic
      diagnosis of CCD in the future.

PMID- 29058296
TI  - Research and application of transnasal transesophageal echocardiography probe.
AB  - The intubation of conventional transesophageal echocardiography (TEE) probes into
      patients causes serious esophagus irritation, and thus the use of TEE probes in
      pediatric practice is limited. In this study, we aimed at the development of a
      special probe which could be inserted through the nasopharyngeal cavity into the
      esophagus to obtain the same high-quality echocardiography images as those
      obtained by conventional TEE and improve patients' experience. During the
      examination, the patients felt relaxed for a longer time and cooperated with the
      sonographers in the process of cardiac catheterization conducted in the surgery
      room or the intensive care unit (ICU), resulting in improved accuracy of the
      diagnosis and timely administration of appropriate treatment. Two years ago,
      Prof. Xin-fang WANG put theories into practice by inserting the probe through the
      nasal cavity and pharynx into the esophagus of volunteers to successfully detect
      the heart and great vessels at the retrocardiac space. Later, Prof. Ming-xing XIE
      performed the transnasal TEE examination in 12 atrial septal defect (ASD)
      patients and proved the safety and reliability of this method, which could become
      a new way for clinical diagnosis and treatment.

PMID- 29058295
TI  - Effects of high frequency repetitive transcranial magnetic stimulation on KCC2
      expression in rats with spasticity following spinal cord injury.
AB  - The effect of high-frequency repetitive transcranial magnetic stimulation (rTMS)
      on potassium- chloride cotransporter-2 (KCC2) protein expression following spinal
      cord injury (SCI) and the action mechanism were investigated. SCI models were
      established in SD rats. Five groups were set up randomly: normal control group,
      SCI 7-day (7D) model group, SCI 14-day (14D) model group, SCI-7D rTMS group and
      SCI-14D rTMS group (n=5 each). The rats in SCI rTMS groups were treated with 10
      Hz rTMS from 8th day and 15th day after SCI respectively, once every day, 5 days
      every week, a total of 4 weeks. After the model establishment, motor recovery and
      spasticity alleviation were evaluated with BBB scale once a week till the end of
      treatment. Finally, different parts of tissues were dissected out for detection
      of variations of KCC2 protein using Western blotting and polymerase chain
      reaction (PCR) technique. The results showed that the BBS scores after treatment
      were significantly higher in SCI-7D rTMS group than in SCI-14D rTMS group
      (P<0.05). As compared with normal control groups, The KCC2 protein in SCI model
      groups was down-regulated after SCI, and the decrease was much more significant
      in SCI-14D model group than in SCI-7D group (P<0.05). As compared with SCI model
      groups, KCC2 protein in rTMS groups was up-regulated after the treatment
      (P<0.05). The up-regulation of KCC2 protein content and expression was more
      obvious in SCI-7D rTMS group than in SCI-14D rTMS group (P<0.05). It was
      concluded that 10 Hz rTMS can alleviate spasticity in rats with SCI, which might
      be attributed to the up-regulation of KCC2 protein. It was also suggested that
      the high-frequency rTMS treatment after SCI at early stage might achieve more
      satisfactory curative effectiveness.

PMID- 29058297
TI  - Does hospital ownership influence hand hygiene compliance?
AB  - The issue as to whether hospital ownership has an impact on the quality of care
      has long been a serious concern. Hand hygiene (HH) compliance is regarded as an
      important indicator of the quality of care in the control of hospital-acquired
      infections. However, little information is available on whether hospital
      ownership influences HH compliance. In this study, of 229 hospitals selected from
      Hubei province in China, 152 were public and 77 were private hospitals. A total
      of 23 652 healthcare workers (HCWs) were surveyed, using a convenience sampling.
      HH compliance, the WHO's "My Five Moments for hand hygiene" (5MHH), among HCWs,
      together with the factors of hospital ownership, training frequency, bed
      occupancy rates, etc. were collected. Univariate analysis and ordinal logistic
      regression analysis were used to analyze factors affecting HH compliance.
      Overall, HH compliance rates were 67% and 79% for public and private hospitals,
      respectively. The HH compliance rates of HCWs and 5MHH were between 55% and 95%,
      and influenced by hospital ownership (P<0.05), excluding compliance rate at the
      moment after body fluid exposure, and other influence factors included training
      frequency and bed occupancy rate (P<0.05). HH compliance is better in private
      than in public hospitals. Hospital ownership is a significant factor affecting HH
      compliance, in addition to training frequency and bed occupancy rate.

PMID- 29058298
TI  - Pharmacokinetics and tolerability of oral dosage forms of huperzine a in healthy
      Chinese male volunteers: a randomized, single dose, three-period, six-sequence
      crossover study.
AB  - Huperzine A is a potent, reversible, and blood-brain barrier permeable
      acetylcholinesterase inhibitor. The aim of this study was to compare the
      pharmacokinetics, tolerability, and bioavailability of two formulations with the
      established reference formulation of huperzine A in a fasting, healthy Chinese
      male population. This was a randomized, single-dose, 3-period, 6-sequence
      crossover study. The plasma concentrations of huperzine A were determined by
      liquid chromatography tandem mass spectrometry. Tolerability was assessed based
      on subject interview, vital sign monitoring, physical examination, and routine
      blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference
      drug were Cmax, 1.550 (0.528) ng/mL; t1/2, 12.092 (1.898) h; AUC0-72h, 17.550
      (3.794) ng.h/mL. Those of the test formulation A and test formulation B were
      Cmax, 1.412 (0.467), 1.521 (0.608) ng/mL; t1/2, 12.073 (2.068), 12.271 (1.678) h;
      AUC0-72h, 15.286 (3.434) ng.h/mL, 15.673 (3.586) ng.h/mL. The 90% confidence
      intervals for the AUC0-72h and Cmax were between 0.80 and 1.25. No adverse events
      were reported by the subjects or found with results of clinical laboratory test.
      The test and reference products met the regulatory criteria for bioequivalence in
      these fasting, healthy Chinese male volunteers. All three formulations appeared
      to be well tolerated.

PMID- 29058299
TI  - Detection of low-abundance point mutations by competitive strand assisted
      endonuclease IV signal amplification system.
AB  - Genetic mutations are important molecular biomarkers for cancer diagnosis and
      surveillance. Therefore, the development of methods for mutation detection
      characterized with straightforward, highly specific and sensitive to low-level
      mutations within various sequence contexts is extremely needed. Although some of
      the currently available methods have shown very encouraging results, their
      discrimination efficiency is still very low. Herein, we demonstrate a fluorescent
      probe coupled with blocker and property of melting temperature discrimination,
      which is able to identify the presence of known or unknown single-base variations
      at abundances down to 0.1% within 20 min. The discrimination factors between the
      perfect-match target and single-base mismatched target are determined to be 10.15
      38.48. The method is sequence independent, which assures a wide range of
      application. The new method would be an ideal choice for high-throughput in vitro
      diagnosis and precise clinical treatment.

PMID- 29058300
TI  - Trisomy 21 with t(5; 11) chromosomal translocation as new unfavorable cytogenetic
      abnormalities in pediatric acute myeloid leukemia type M2: One case report of
      nine-year follow-up and literature review.
AB  - We report one case of pediatric acute myeloid leukemia type 2 (AML-M2) who
      presented with karyotypic aberration of trisomy 21 with the t(5;11) chromosomal
      translocation. The patient achieved complete remission after two cycles of
      chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up
      cytogenetic analysis from bone marrow cell cultures demonstrated a normal
      karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic
      abnormalities of trisomy 21 with t(5;11) reappeared. It was concluded that
      trisomy 21 with t(5; 11) is a new unfavorable cytogenetic aberration in AML-M2.

PMID- 29058301
TI  - Cancer-Testis Antigens as New Candidate Diagnostic Biomarkers for Transitional
      Cell Carcinoma of Bladder.
AB  - To evaluate the diagnostic potential of 23 candidate genes, belonging to a
      category of tumor-specific antigens known as cancer-testis antigens (CTAs), in
      transitional cell carcinoma (TCC) patients. The expression of 16 known candidate
      CTAs and seven testis restricted/selective genes, predominantly expressed in the
      testis, was evaluated by reverse transcriptase-polymerase chain reaction (RT
      PCR). Urinary exfoliated cells (UECs) and cancerous tissues of 73 TCC patients
      were used as cases, while 25 tumor-free adjacent bladder tissue specimens along
      with bladder tissue specimens and UECs of five non-TCC individuals were analyzed
      as controls. Among the known CTAs only MAGEA3, MAGEB4, TSGA10, PIWIL2, OIP5, and
      ODF4 were expressed specifically in TCC tissues and UEC samples. ACTL7A, AURKC,
      and CGB2 were testis-restricted/selective genes that indicated specific
      expression in cases in comparison to controls. MAGEA3, MAGEB4, and ODF4 mRNA was
      detectable in more than 50% of both TCC tissues, and UEC samples. Slight
      differences were detected in the mRNA expression pattern of candidate genes
      between the UEC samples and tumor tissues. Different panels formed by
      combinations of these genes can show up to 95.9% and 94.5% of positivity in TCC
      tissues and UEC samples, respectively, suggesting their diagnostic and
      surveillance potential. Meanwhile the RT-PCR assay of at least MAGEA3, MAGEB4,
      and ODF4 may be particularly useful for diagnostic and surveillance of TCC in the
      form of a multi-biomarker panel.

PMID- 29058302
TI  - Switching Between Biological Treatments in Psoriatic Arthritis: A Review of the
      Evidence.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy. Therapy with
      anti-tumor necrosis factor (TNF)-alpha agents represents the first therapeutic
      choice for moderate and severe forms; however, PsA patients can experience anti
      TNFalpha failure, lack of efficacy, or adverse events. Several evidences exist on
      the effectiveness of switching among different TNFalpha inhibitors, and we
      reviewed the published data on the effectiveness of anti-TNFalpha first-, second-
      and third-line. Most of the studies report that the main reason for switching to
      a second anti-TNFalpha agent is represented by lack of efficacy (primary or
      secondary) and, more rarely, adverse events. Switchers receiving their second
      anti-TNFalpha agent have considerably poorer responses compared with non
      switchers. Survival of anti-TNFalpha treatment appears to be superior in PsA
      patients when compared with rheumatoid arthritis patients. Switching from anti
      TNF agents to ustekinumab or secukinumab or apremilast can represent a valid
      alternative therapeutic strategy.

PMID- 29058303
TI  - Transmucosal Delivery of Nicotine in Combination with Tincture of Benzoin
      Inhibits Apoptosis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to test the hypothesis that
      tincture of benzoin (TOB) facilitates immediate transmucosal nicotine absorption
      while simultaneously promoting a safe and sustained delivery of the nicotine.
      METHODS: In combination with TOB, nicotine toxicity and diffusion across human
      mucosal cells were measured using a 3-D human mucosal tissue model. RESULTS:
      Nicotine was delivered 2.1 times more quickly in combination with TOB than in
      combination with saline (p < 0.05). Despite the increased diffusion, nicotine in
      combination with TOB significantly increased mucosal cell survival (p < 0.05) by
      reducing the release of mitochondrial cytochrome c into the cytoplasm when
      compared with nicotine without TOB. The average percentage distribution of
      cytochrome c in the cytosolic fraction over time of nicotine + 79% ethyl alcohol
      (ETOH) versus nicotine plus TOB (79% ETOH) was significantly different over 120
      min (60.0 +/- 29.9% cytosol, 16.1 +/- 9.4% cytosol, p = 0.03). Related to the
      reduction of cytochrome c release into the cytoplasm, TOB suppressed caspase-3
      and -9 activity, thereby preventing intrinsic apoptosis and providing
      cytoprotection of the mucosal cells (ETOH + nicotine vs ETOH + nicotine + TOB: p
      = 0.008 for caspase 3, p < 0.001 for caspase 9). CONCLUSION: Two hours of TOB (17
      24% benzoin, 79% ETOH) plus nicotine promotes diffusion of nicotine across human
      mucosal cells and simultaneously prevents human mucosal cell toxicity by
      inhibiting cytochrome c release into the cytosol, thereby preventing caspase 3
      and 9 activity and subsequent intrinsic apoptosis.

PMID- 29058304
TI  - Serious Adverse Events Among SPRINT Trial Participants Taking Statins at
      Baseline.
AB  - BACKGROUND: Real-world evidence of statin side effects is potentially biased
      because statin use is neither randomized nor unblinded. An innovative study
      design can mitigate these biases. For example, in the recent ASCOT-LLA trial,
      patient-reported adverse events such as muscle pain and weakness were higher in
      the non-randomized and non-blinded setting than in the randomized, blinded
      setting. Less optimally, secondary re-analysis of clinical trials in which statin
      use is recorded and in which serious adverse events (SAEs) are adjudicated may be
      conducted. OBJECTIVE: The objective of this study was to evaluate SAEs by statin
      use at baseline among participants in the SPRINT blood pressure (BP) management
      trial. METHODS: Unadjusted overall SAE and treatment-related SAE rates by statin
      use as well as adjusted hazard ratios for statin use were computed in four
      cohorts [by baseline clinical cardiovascular disease (CVD), by intervention arm].
      RESULTS: Statin use at baseline was not associated with higher overall or
      treatment-related SAE rates among (1) those without pre-existing CVD, regardless
      of BP arm, nor among (2) those randomized to standard BP management, regardless
      of pre-existing CVD. Among higher risk patients with existing clinical CVD
      randomized to intensive BP management, a small but significant increase in
      overall SAE rate was found among those taking statin at baseline. CONCLUSIONS: In
      SPRINT, generally statin use was not associated with increased risk of reporting
      SAEs. Only statin use by higher risk patients was associated with more overall
      SAEs. Confounding by clinical CVD and the polytherapy of intensive BP management
      may explain this.

PMID- 29058305
TI  - Erratum to &#8220;Adaptation of the Nomophobia Questionnaire (NMP-Q) to Spanish
      in a sample of adolescents&#8221.

PMID- 29058306
TI  - Digital image analysis of the tissue surface areas of site-designated and
      bilaterally pooled prostate biopsies.
AB  - Initial reports about the length of bilaterally pooled biopsies showed alarming
      tissue loss compared to individual biopsies, but the current understanding of
      "noodle biopsies" and better embedding techniques may have improved their
      quality. Here, we implemented digital image analysis to study the differences in
      tissue surface areas between individual and pooled cores. Prostate biopsy reports
      from 1242 consecutive patients were reviewed. Urologist-dependent bias on the
      biopsy quality was eliminated by identifying four urologists who submitted
      equally individual and bilaterally pooled biopsies. Digital image analysis was
      applied to the tissue surface areas of 936 virtual slides containing 1440 biopsy
      cores (12 cores per patient x 120 patients) taken by the four urologists. The
      median (range) surface areas were 73.8 mm2 (40.1-102.5) for the site-designated
      (n=57) and 77.1 mm2 (49.5-119.2) for the bilaterally pooled biopsies (n=63)
      (p=0.19). For three urologists, the median surface areas were 69.5 mm2 (60.4
      93.2), 75.5 mm2 (48.2-98.7) and 78.2 mm2 (47.1-92.7) for the site-designated and
      79.2 mm2 (49.5-116.4), 69.3mm2 (49.6-119.2) and 79.2 mm2 (55.1-96.7) for the
      pooled biopsies, respectively (p=0.58-0.75). For one urologist, the median
      surface area was marginally higher for the pooled biopsies, 68.1 mm2 (40.1-102.5)
      vs. 81.6 mm2 (62.7-108.8) (p=0.03). In conclusion, the histological yields of
      individual and pooled prostate biopsies were practically equal. The results
      should not be considered as a recommendation to increasingly submit unspecified
      bilateral cores but to encourage pathology laboratories to embed and cut all
      received prostate biopsies with special attention, regardless of submission type.

PMID- 29058307
TI  - Genetic immunization with mouse thyrotrophin hormone receptor plasmid breaks self
      tolerance for a murine model of autoimmune thyroid disease and Graves'
      orbitopathy.
AB  - Experimental models of Graves' hyperthyroid disease accompanied by Graves'
      orbitopathy (GO) can be induced efficiently in susceptible inbred strains of mice
      by immunization by electroporation of heterologous human TSH receptor (TSHR) A
      subunit plasmid. In this study, we report on the development of a bona fide
      murine model of autoimmune Graves' disease induced with homologous mouse TSHR A
      subunit plasmid. Autoimmune thyroid disease in the self-antigen model was
      accompanied by GO and characterized by histopathology of hyperplastic glands with
      large thyroid follicular cells. Examination of orbital tissues showed significant
      inflammation in extra-ocular muscle with accumulation of T cells and macrophages
      together with substantial deposition of adipose tissue. Notably, increased levels
      of brown adipose tissue were present in the orbital tissue of animals undergoing
      experimental GO. Further analysis of inflammatory loci by 19 F-magnetic resonance
      imaging showed inflammation to be confined to orbital muscle and optic nerve, but
      orbital fat showed no difference in inflammatory signs in comparison to control
      beta-Gal-immunized animals. Pathogenic antibodies induced to mouse TSHR were
      specific for the self-antigen, with minimal cross-reactivity to human TSHR.
      Moreover, compared to other self-antigen models of murine Graves' disease induced
      in TSHR knock-out mice, the repertoire of autoantibodies to mouse TSHR generated
      following the breakdown of thymic self-tolerance is different to those that arise
      when tolerance is not breached immunologically, as in the knock-out models.
      Overall, we show that mouse TSHR A-subunit plasmid immunization by
      electroporation overcomes tolerance to self-antigen to provide a faithful model
      of Graves' disease and GO.

PMID- 29058309
TI  - Interplay between silica deposition and viability during the life span of sorghum
      silica cells.
AB  - Silica cells are specialized epidermal cells found on both surfaces of grass
      leaves, with almost the entire lumen filled with solid silica. The mechanism
      precipitating silicic acid into silica is not known. Here we investigate this
      process in sorghum (Sorghum bicolor) leaves. Using fluorescent confocal
      microscopy, we followed silica cells' ontogeny, aiming to understand the fate of
      vacuoles and nuclei. Correlating the confocal and scanning electron microscopy,
      we timed the initiation of silica deposition in relation to cell's viability.
      Contrary to earlier reports, silica cells did not lose their nucleus before
      silica deposition. Vacuoles in silica cells did not concentrate silicic acid.
      Instead, postmaturation silicification initiated at the cell periphery in live
      cells. Less than 1% silica cells showed characteristics of programmed cell death
      in the cell maturation zone. In fully elongated mature leaves, 2.4% of silica
      cells were nonsilicified and 1.6% were partially silicified. Silica deposition
      occurs in the paramural space of live silica cells. The mineral does not kill the
      cells. Instead, silica cells are genetically programmed to undergo cell death
      independent of silicification. Fully silicified cells seem to have nonsilicified
      voids containing membrane remains after the completion of the cell death
      processes.

PMID- 29058308
TI  - Analysis of the regulatory function of natural killer cells from patients with
      systemic lupus erythematosus.
AB  - Natural killer (NK) cells participate in the regulation of the immune response.
      However, the immunomodulatory function of NK cells in systemic lupus
      erythematosus (SLE) is not well understood. The aim of this study was to evaluate
      the regulatory function of NK cells in SLE patients and to identify the NK cells
      involved in the pathogenesis of this complex disease. We analysed the expression
      of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3- CD56+ )
      from SLE patients, as well as the numbers of human leucocyte antigen D-related
      (HLA-DR)/CD11c+ NK cells. In addition, NK cell regulatory function was assessed
      by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE
      patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2)+ ,
      CD86+ and CD134+ NK cells. Furthermore, NK cells from SLE patients induced higher
      levels of DC lysis. We were able to identify a new subset of NK cells co
      expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE
      patients when compared with controls. We have identified an expanded new subset
      of NK cells in SLE patients. This is the first study, to our knowledge, which
      demonstrates that NK cells in SLE patients have an altered phenotype with a high
      expression of receptors characteristic of dendritic cells. Our results suggest
      that the impairment in the regulatory function of NK cells, together with the
      increased number of DC-like NK cells, could play an important role in the
      development of SLE and highlight the importance of NK cells as a future
      therapeutic target.

PMID- 29058311
TI  - APETALA 2-domain-containing transcription factors: focusing on abscisic acid and
      gibberellins antagonism.
AB  - The phytohormones abscisic acid (ABA) and gibberellin (GA) antagonistically
      mediate diverse plant developmental processes including seed dormancy and
      germination, root development, and flowering time control, and thus the optimal
      balance between ABA and GA is essential for plant growth and development.
      Although more than a half and one century have passed since the initial
      discoveries of ABA and GA, respectively, the precise mechanisms underlying ABA-GA
      antagonism still need further investigation. Emerging evidence indicates that two
      APETALA 2 (AP2)-domain-containing transcription factors (ATFs), ABI4 in
      Arabidopsis and OsAP2-39 in rice, play key roles in ABA and GA antagonism. These
      two transcription factors precisely regulate the transcription pattern of ABA and
      GA biosynthesis or inactivation genes, mediating ABA and GA levels. In this
      Viewpoint article, we try to shed light on the effects of ATFs on ABA-GA
      antagonism, and summarize the overlapping but distinct biological functions of
      these ATFs in the antagonism between ABA and GA. Finally, we strongly propose
      that further research is needed into the detailed roles of additional numerous
      ATFs in ABA and GA crosstalk, which will improve our understanding of the
      antagonism between these two phytohormones.

PMID- 29058310
TI  - A novel risk score for severe ARDS patients undergoing ECMO after retrieval from
      peripheral hospitals.
AB  - BACKGROUND: Extracorporeal Membrane Oxygenation in severe ARDS unresponsive to
      conventional protective ventilation is associated with elevated costs, resource
      and complications, and appropriate risk stratification of candidate patients
      could be useful to recognize those more likely to benefit from ECMO. We aimed to
      derive a new outcome prediction score for patients retrieved by our ECMO team
      from peripheral centers, including systematic echocardiographic evaluation before
      ECMO start. METHODS: Sixty-nine consecutive patients with refractory ARDS
      requiring ECMO transferred from peripheral centers to our ICU (a tertiary ECMO
      referral center), from 1 October 2009 to 31 December 2015, were assessed.
      RESULTS: All patients were transported on ECMO (distance, median 77, range 4-456
      km) The mortality rate was 41% (28/69). Our new risk score included age >= 42
      years, BMI < 31 kg/m2 , RV dilatation, and pH < 7.35. The proposed cut off
      (Youden's index method) of nine had a sensitivity of 96% and a specificity of 30%
      (AUC-ROC: 0.85, 95% CI: 0.76-0.94, P < 0.001). When assessing the discriminatory
      ability of our risk score in the population of local patients, survivors had a
      mean value of 15.4 +/- 8.6, whereas non-survivors showed a mean value of 20.1 +/-
      7.4 (P < 0.001). CONCLUSIONS: Our new risk score shows good discriminatory
      ability both in patients retrieved from peripheral centers and in those implanted
      at our center. This score includes variables easily available at bedside, and,
      for the first time, a pathophysiologic element, RV dilatation.

PMID- 29058312
TI  - Tree size and climatic water deficit control root to shoot ratio in individual
      trees globally.

PMID- 29058313
TI  - The role of social risk in an early preventative care programme for infants born
      very preterm: a randomized controlled trial.
AB  - AIM: To examine the differential effects of an early intervention programme for
      infants born preterm on neurodevelopment and parental mental health according to
      family social risk. METHOD: One hundred and twenty infants born earlier than 30
      weeks' gestation were randomized to early intervention (n=61) or control groups
      (n=59). Cognitive, language, and motor outcomes were assessed by blinded
      assessors at 2 years, 4 years, and 8 years, and primary caregivers completed
      questionnaires on their anxiety and depression. Outcomes at each time point were
      compared between groups using linear regression with an interaction term for
      social risk (higher/lower). RESULTS: There was evidence of interactions between
      intervention group and social risk for cognition at 2 years and 4 years, motor
      function at 4 years, and language at 8 years, with a greater intervention effect
      in children from higher social risk environments. In contrast, the impact of
      early intervention on parental depressive symptoms was greater for parents of
      lower social risk than for those of higher social risk. INTERPRETATION: Effects
      of early intervention on outcomes for children born preterm and their caregivers
      varied according to family social risk. Family social risk should be considered
      when implementing early intervention programmes for children born preterm and
      their families. WHAT THIS PAPER ADDS: Intervention is associated with better
      early cognitive functioning for children in higher social risk families. Positive
      effects of intervention for the high risk group were not sustained at school-age.
      Intervention has a greater effect on primary caregiver mental health in the lower
      social risk group compared with higher social risk.

PMID- 29058314
TI  - T cell suppression in the bone marrow of visceral leishmaniasis patients: impact
      of parasite load.
AB  - Visceral leishmaniasis (VL) is a disseminated and lethal disease of reticulo
      endothelial system caused by protozoan parasites Leishmania donovani and L.
      infantum, which are known to induce host T cell suppression. To understand the
      impact of parasite load on T cell function, the present was focused on parasite
      load with T cell function in bone marrow of 26 VL patients. We observed
      significant enrichment of forkhead box protein 3 (FoxP3)+ (P = 0.0003) and
      interleukin (IL)-10+ FoxP3+ regulatory T cells (Treg ) (P = 0.004) in the bone
      marrow (BM) of patients with high parasite load (HPL) compared with low parasite
      load (LPL). Concordantly, T effector cells producing interferon (IFN)-gamma (P =
      0.005) and IL-17A (P = 0.002) were reduced in the BM of HPL. Blocking of Treg 
      cell derived suppressive cytokines [(IL-10 and transforming growth factor (TGF)
      beta] rescued the effector T cells and their functions. However, it was observed
      that TGF-beta levels were dominant, favouring Treg cell differentiation.
      Furthermore, the low ratio of IL-6/TGF-beta favours the suppressive milieu in HPL
      patients. Here we show the change in levels of various cytokines with the
      parasitic load during active VL, which could be helpful in devising newer
      immunotherapeutic strategies against this disease.

PMID- 29058315
TI  - Atelectasis is inversely proportional to transpulmonary pressure during weaning
      from ventilator support in a large animal model.
AB  - BACKGROUND: In mechanically ventilated, lung injured, patients without
      spontaneous breathing effort, atelectasis with shunt and desaturation may appear
      suddenly when ventilator pressures are decreased. It is not known how such a
      formation of atelectasis is related to transpulmonary pressure (PL ) during
      weaning from mechanical ventilation when the spontaneous breathing effort is
      increased. If the relation between PL and atelectasis were known, monitoring of
      PL might help to avoid formation of atelectasis and cyclic collapse during
      weaning. The main purpose of this study was to determine the relation between PL
      and atelectasis in an experimental model representing weaning from mechanical
      ventilation. METHODS: Dynamic transverse computed tomography scans were acquired
      in ten anaesthetized, surfactant-depleted pigs with preserved spontaneous
      breathing, as ventilator support was lowered by sequentially reducing inspiratory
      pressure and positive end expiratory pressure in steps. The volumes of gas and
      atelectasis in the lungs were correlated with PL obtained using oesophageal
      pressure recordings. Work of breathing (WOB) was assessed from Campbell diagrams.
      RESULTS: Gradual decrease in PL in both end-expiration and end-inspiration caused
      a proportional increase in atelectasis and decrease in the gas content (linear
      mixed model with an autoregressive correlation matrix; P < 0.001) as the WOB
      increased. However, cyclic alveolar collapse during tidal ventilation did not
      increase significantly. CONCLUSION: We found a proportional correlation between
      atelectasis and PL during the 'weaning process' in experimental mild lung injury.
      If confirmed in the clinical setting, a gradual tapering of ventilator support
      can be recommended for weaning without risk of sudden formation of atelectasis.

PMID- 29058316
TI  - Does Enrollment in High-Deductible Health Plans Encourage Price Shopping?
AB  - OBJECTIVE: To investigate whether enrollment in high-deductible health plans
      (HDHPs) led enrollees to choose lower-priced providers for office visits and
      laboratory tests. STUDY SETTING: Claims data from more than 40 large employers.
      STUDY DESIGN: We compared the change in price for office visits and laboratory
      tests for enrollees who switched to HDHPs versus enrollees who remained in
      traditional plans. We estimated separate models for enrollees who changed
      providers versus those who remained with the same provider to disentangle the
      effects of HDHPs on provider choice and negotiated prices. DATA COLLECTION:
      Claims data from 2004 to 2010 on 1.8 million enrollees. PRINCIPAL FINDINGS: After
      enrollment in HDHPs, 28 percent of enrollees changed physicians for office visits
      (compared to 19 percent in the Traditional Plan group, p < .01); however, this
      did not result in a statistically significant reduction in price for office
      visits. About 25 percent of enrollees changed providers for laboratory tests
      (compared to 23 percent in the Traditional Plan group, p < .01), resulting in
      savings of about $2.09 or a 12.8 percent reduction in price per laboratory test.
      We found that HDHPs had lower negotiated prices for office visits but not for
      laboratory tests. CONCLUSIONS: High-deductible health plan enrollment may shift
      enrollees to lower cost providers, resulting in modest savings.

PMID- 29058317
TI  - Doxorubicin hinders DNA condensation promoted by the protein bovine serum albumin
      (BSA).
AB  - In this work, we have studied the interaction between the anticancer drug
      doxorubicin (doxo) and condensed DNA, using optical tweezers. To perform this
      task, we use the protein bovine serum albumin (BSA) in the working buffer to
      mimic two key conditions present in the real intracellular environment: the
      condensed state of the DNA and the abundant presence of charged macromolecules in
      the surrounding medium. In particular, we have found that, when doxo is
      previously intercalated in disperse DNA, the drug hinders the DNA condensation
      process upon the addition of BSA in the buffer. On the other hand, when bare DNA
      is firstly condensed by BSA, doxo is capable to intercalate and to unfold the DNA
      condensates at relatively high concentrations. In addition, a specific
      interaction between BSA and doxo was verified, which significantly changes the
      chemical equilibrium of the DNA-doxo interaction. Finally, the presence of BSA in
      the buffer stabilizes the double-helix structure of the DNA-doxo complexes,
      preventing partial DNA denaturation induced by the stretching forces.

PMID- 29058318
TI  - Seizure outcome after corpus callosotomy in a large paediatric series.
AB  - AIM: To describe 20 years of experience with corpus callosotomy at Great Ormond
      Street Hospital for Children, London and the Children's Hospital at Westmead,
      Sydney. METHOD: Records of patients who underwent corpus callosotomy between
      January 1995 and December 2015 were reviewed. Complications of surgery and
      changes in seizure type and frequency, injuries, and use of antiepileptic drugs
      were recorded. Drop attacks were analysed using Kaplan-Meier event-free survival
      curves. Multivariable regression analysis was used to assess the effect of
      clinical characteristics on outcome at last follow-up. RESULTS: Inclusion
      criteria were met for 55 patients younger than 18 years of age. Median follow-up
      length was 36 months. At the last follow-up, 26 out of 55 patients (47%) had rare
      or no drop attacks. In those without a good outcome at final follow-up, 26 out of
      29 (90%) had drop attacks return within 12 months of surgery. There were no
      preoperative predictors of developing drop attacks postoperatively. The median
      number of antiepileptic drugs significantly reduced from three to two. Transient
      neurological complications were experienced by 11 out of 55 patients (20%) and 6
      out of 55 patients had surgical complications (11%). INTERPRETATION: Corpus
      callosotomy is a well-tolerated procedure that is effective at reducing the
      severity of drop attacks in paediatric patients. Drop attacks that do return are
      likely to do so within 12 months and the number of antiepileptic drugs can be
      significantly reduced. WHAT THIS PAPER ADDS: Corpus callosotomy is an effective
      palliative treatment and well tolerated in children. Good outcomes for the first
      12 months after surgery were likely to continue. The number of antiepileptic
      drugs can be significantly reduced after corpus callosotomy. Patients with fewer
      than three types of seizure had better outcomes. There were fewer injuries from
      drop attacks after surgery.

PMID- 29058319
TI  - How many cases of disease in a pedigree imply familial disease?
AB  - The ability to perform whole-exome and, increasingly, whole-genome sequencing on
      large numbers of individuals has led to increased efforts to identify rare
      genetic variants that affect the risk of both common and rare diseases. In such
      applications, it is important to identify families that are segregating the rare
      variants of interest. For rare diseases or rare familial forms of common
      diseases, pedigrees with multiple affected members are clearly harbouring risk
      variants. For more common diseases, however, it may be unclear whether a family
      with a few affected members is segregating a familial disease, is the result of
      multiple sporadic cases, or is a mixture of familial cases and phenocopies. We
      provide calculations for the probability that a family is harbouring familial
      disease, presented in general terms that admit working guidelines for selecting
      families for current sequencing studies. Using examples motivated by our own
      studies of thyroid cancer and published studies of colorectal cancer, we show
      that for common diseases, families with exactly two affected first-degree
      relatives have only a moderate probability of segregating familial disease, but
      this probability is higher for families with three or more affected relatives,
      and those families should therefore be prioritised in sequencing studies.

PMID- 29058320
TI  - The transfer of Crel contextual control (same, opposite, less than, more than)
      through equivalence relations.
AB  - According to Relational Frame Theory (RFT) Crel denotes a contextual stimulus
      that controls a particular type of relational response (sameness, opposition,
      comparative, temporal, hierarchical etc.) in a given situation. Previous studies
      suggest that contextual functions may be indirectly acquired via transfer of
      function. The present study investigated the transfer of Crel contextual control
      through equivalence relations. Experiment 1 evaluated the transfer of Crel
      contextual functions for relational responses based on sameness and opposition.
      Experiment 2 extended these findings by evaluating transfer of function using
      comparative Crel stimuli. Both experiments followed a similar sequence of phases.
      First, abstract forms were established as Crel stimuli via multiple exemplar
      training (Phase 1). The contextual cues were then applied to establish arbitrary
      relations among nonsense words and to test derived relations (Phase 2). After
      that, equivalence relations involving the original Crel stimuli and other
      abstract forms were trained and tested (Phase 3). Transfer of function was
      evaluated by replacing the directly established Crel stimuli with their
      equivalent stimuli in the former experimental tasks (Phases 1 and 2). Results
      from both experiments suggest that Crel contextual control may be extended via
      equivalence relations, allowing other arbitrarily related stimuli to indirectly
      acquire Crel functions and regulate behavior by evoking appropriate relational
      responses in the presence of both previously known and novel stimuli.

PMID- 29058321
TI  - Synthesis and structure analysis of ferrocene-containing pseudopeptides.
AB  - Ferrocene with its aromaticity and facile redox properties is an attractive
      moiety to be incorporated into functional moieties. Medicinal applications of
      ferrocene are well known and ferrocene itself shows cytotoxic and antianemic
      properties. In this article, we will describe the synthesis and the structure
      analysis of two pseudopeptides containing a ferrocene moiety as N-terminal group.
      After purification, Fc-l-Phe-d-Oxd-OBn [l-Phe?l-phenylalanine; d-Oxd?(4R,5S)-4
      Methyl-5-carboxy-oxazolidin-2-one] appears as bright brown solid that
      spontaneously forms brown needles. The X-ray diffraction of the crystals shows
      the presence of strong pi interactions between the ferrocenyl moiety and the
      phenyl rings, while no N?H***O?C hydrogen bonds are formed. This result is
      confirmed by FT-IR and 1 H NMR analysis. In contrast, both FT-IR and 1 H NMR
      analysis suggest that Fc-(l-Phe-d-Oxd)2 -OBn forms a turn conformation stabilized
      by intramolecular N?H***O?C hydrogen bonds in solution. Chiroptical
      spectroscopies (ECD and VCD) substantially confirmed the absence of a well
      defined folded structure. The presence of the Fc moiety is responsible for
      specific ECD signals, one of which displayed pronounced temperature dependence
      and is directly related with the helicity assumed by the Fc core. Solid-state ECD
      spectra were recorded and rationalized on the basis of the X-ray geometry and
      quantum-mechanical calculations.

PMID- 29058322
TI  - Influence of different functional ingredients on physical properties, rheology,
      tribology, and oral perceptions of no fat stirred yoghurt.
AB  - : Effects of adding four functional ingredients: inulin, pectin, galacto
      oligosaccharides (GOS), and beta glucan on physical, rheology, tribology, and
      sensory characteristics of skim (0.1% fat) stirred yoghurt were studied. Three
      levels of each ingredient were chosen: inulin (7, 8, and 9%), pectin (0.2, 0.25,
      and 0.3%), GOS (9.1, 11.3, and 13.6%), and beta glucan (0.1, 0.2, and 0.3%).
      Among the investigated ingredients, inulin and GOS appeared to be preferable
      choices due to their ability to both reduce syneresis and slightly increase
      sample lubrication while maintaining texture, rheology, and sensory
      characteristics of skim yoghurt. Pectin and beta glucan, conversely, increased
      viscosity and gel strength, slightly increased sample lubrication for the skim
      yoghurt but created large particles (i.e., greater than 100 MUm) in the product
      body. This led to the increase in lumpiness and residual coating while reducing
      smoothness and creaminess of the sample. The observed tribology behaviors of the
      stirred yoghurts were similar to the previous study of pot-set yoghurt whose
      friction curves comprised four friction zones (Nguyen, Kravchuk, Bhandari, and
      Prakash). The sensory characteristics of six selected samples for various texture
      and mouthfeel attributes obtained from a trained panel were in agreement with
      particle size, rheology, and tribology characteristics of the yoghurt samples.
      PRACTICAL APPLICATIONS: With the increasing demand for low fat and functional
      food, there is a need to understand the impact of adding functional ingredients
      in low fat yoghurt to satisfy consumers' requirements. This study investigates
      the effects of these functional ingredients at different dosages on physical,
      rheology, tribology, and sensory characteristics of skim (0.1% fat) stirred
      yoghurt. The results from this study may guide use of functional ingredients in
      yoghurt production.

PMID- 29058323
TI  - CD1a-positive cutaneous mastocytosis: Electron microscopic evidence of
      pleomorphic mast cell proliferation.

PMID- 29058324
TI  - Treatment of molluscum contagiosum with hydrogen peroxide.

PMID- 29058325
TI  - Itching for nail fashion: chronic urticaria and chronic hand dermatitis secondary
      to acrylate and methacrylate allergy in gel nail varnish.
AB  - Allergic contact dermatitis (ACD) secondary to acrylates and methacrylates is a
      well- described occurrence, particularly in those who wear or handle gel nail
      varnish. Management involves avoidance of the identified allergen. The cause of
      chronic urticaria (CI) is often not identified, and CU is not known to be
      associated with acrylates or methacrylates. We report a case of a 50-year-old
      woman who initially presented with hand dermatitis exacerbated by gel nail
      varnish on a background of CU. Avoiding all nail varnishes because of her ACD
      also resulted in improvement of her CU. To our knowledge, this is the first
      documented case of CU secondary to the acrylates and methacrylates found in nail
      cosmetics.

PMID- 29058326
TI  - Pemphigus vegetans with the manifestations of acrodermatitis continua: A rare
      variant.

PMID- 29058327
TI  - Painful, violaceous plaques in a patient with pruritus.

PMID- 29058328
TI  - Pigmented Bowen disease: A challenging dermoscopic feature due to a traumatic
      disfigurement.

PMID- 29058329
TI  - Presymptomatic genetic diagnosis of two siblings with hereditary angioedema,
      presenting with unusual normal levels of serum C4.

PMID- 29058330
TI  - A congenital naevus in a blaschkoid distribution.

PMID- 29058331
TI  - A relative weights comparison of trauma-related shame and guilt as predictors of
      DSM-5 posttraumatic stress disorder symptom severity among US veterans and
      military members.
AB  - OBJECTIVES: Veterans and military service members have increased risk for post
      traumatic stress disorder (PTSD) and consequent problems with health,
      psychosocial functioning, and quality of life. In this population and others,
      shame and guilt have emerged as contributors to PTSD, but there is a considerable
      need for research that precisely demonstrates how shame and guilt are associated
      with PTSD. This study examined whether a) trauma-related shame predicts PTSD
      severity beyond the effects of trauma-related guilt and b) shame accounts for a
      greater proportion of variance in PTSD symptoms than guilt. DESIGN: We collected
      cross-sectional self-report data on measures of PTSD symptom severity based on
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
      criteria, trauma-related shame, and trauma-related guilt via online survey.
      METHOD: Participants included 61 US veterans and active duty service members.
      Hierarchical multiple regression and relative weights analysis were used to test
      hypotheses. RESULTS: In step 1 of regression analysis, guilt was significantly
      associated with PTSD. However, when shame was added to the model, the effect of
      guilt became non-significant, and only shame significant predicted PTSD. Results
      from relative weights analysis indicated that both shame and guilt predicted
      PTSD, jointly accounting for 46% of the variance in PTSD. Compared to guilt,
      trauma-related shame accounted for significantly more explained variance in PTSD.
      CONCLUSIONS: This study provided evidence that among US veterans and service
      members, trauma-related shame and guilt differ in their association with PTSD and
      that trauma-related shame, in particular, is associated with the severity of
      PTSD. PRACTITIONER POINTS: Trauma-related shame and guilt explained almost half
      of the observed variance in PTSD symptom severity among this sample of US
      military veterans and service members. Trauma-related shame and guilt each made a
      unique contribution to PTSD severity after accounting for the similarity between
      these two emotions; however, shame was particularly associated with increased
      PTSD severity. These results highlight the importance of assessing and addressing
      trauma-related shame and guilt in PTSD treatment among military populations. We
      suggest that emotion- and compassion-focused techniques may be particularly
      relevant for addressing trauma-related shame and guilt. Limitations of the study
      Cross-sectional data does not allow for determination of causal relationships.
      Although sufficiently powered, the sample size is small. The present sample self
      selected to participate in a study about stress and emotions.

PMID- 29058332
TI  - Learning support interventions for Year 1 medical students: a review of the
      literature.
AB  - CONTEXT: The journey through medical school can be challenging, especially for
      undergraduate medical students who must deal with a demanding curriculum, coupled
      with the demands of transitioning into adulthood. Despite experiencing learning
      challenges, most students succeed with appropriate learning support. Many medical
      schools offer learning support programmes, particularly in the latter years, but
      it has been suggested that such support could be more beneficial, especially
      during the initial years. OBJECTIVES: This review explores learning support
      intervention programmes used to address learning challenges and deficits in the
      first year of medical school. Additionally, we propose a potential framework for
      supporting learning during the first year of medical school. METHODS: We searched
      PubMed, Web of Science, MEDLINE, CINAHL (Cumulative Index to Nursing and Allied
      Health Literature), ERIC (Educational Resources Information Centre), Academic
      Search Premier and Google Scholar using the search terms 'learning support',
      'learning challenge', 'remediation', 'change', 'medical education' and 'first
      year'. We developed and used a review matrix to record the main elements of each
      article. We also coded the matrix to identify emerging themes. RESULTS: The main
      themes that emerged from the study were 'intervention approaches', 'area of
      intervention', 'intervention strategies', 'intervention dose' and 'intervention
      outcomes'. INTERVENTIONS: (i) used proactive-deficit, reactive-deficit and
      proactive-developmental approaches; (ii) addressed content knowledge, academic
      success skills, personal and professional skills and programme-related elements;
      (iii) utilised faculty staff-facilitated, peer-facilitated, support staff
      facilitated, experiential placement, self-study and reduced-load strategies; (iv)
      varied in length from 5 weeks to 2 years, and (v) generally showed positive
      results. CONCLUSIONS: This review has identified the main components of learning
      support interventions used for Year 1 medical students. Interventions, however,
      are generally not grounded on empirical assessment that elucidates the nature of
      the challenges faced by students. Future research should provide empirical
      understanding of the learning challenges to be addressed.

PMID- 29058333
TI  - Ecthyma gangrenosum, an important cutaneous infection to recognize in the
      immunosuppressed patient.

PMID- 29058334
TI  - Dyskeratosis congenita associated with congenital hypothyroidism.

PMID- 29058335
TI  - Generalized eruptive keratoacanthoma with vitiligo followed by the development of
      prurigo nodularis: A case report and published work review.
AB  - Herein, we report a unique case of generalized eruptive keratoacanthoma (GEKA) in
      a 47-year-old Chinese man presenting with extensive pruritic papules and nodules
      accompanied by oral lesions. He also had a 2-year history of vitiligo and long
      term experience of working outdoors. Biopsies were consistent with
      keratoacanthoma . Interestingly, prurigo nodularis (PN) was found in
      histopathology at 1-year follow up. To our knowledge, this is the first report
      describing a case of GEKA with oral lesions complicated with vitiligo and
      developed with PN.

PMID- 29058336
TI  - Localized cluster of nodules in childhood.

PMID- 29058337
TI  - When I say ... affordance perception.

PMID- 29058338
TI  - Broad Chromatin Domains: An Important Facet of Genome Regulation.
AB  - Chromatin composition differs across the genome, with distinct compositions
      characterizing regions associated with different properties and functions.
      Whereas many histone modifications show local enrichment over genes or regulatory
      elements, marking can also span large genomic intervals defining broad chromatin
      domains. Here we highlight structural and functional features of chromatin
      domains marked by histone modifications, with a particular emphasis on the
      potential roles of H3K27 methylation domains in the organization and regulation
      of genome activity in metazoans.

PMID- 29058339
TI  - Linking Mitochondria and Synaptic Transmission: The CB1 Receptor.
AB  - CB1 receptors are functionally present within brain mitochondria (mtCB1),
      although they are usually considered specifically targeted to plasma membrane.
      Acute activation of mtCB1 alters mitochondrial ATP generation, synaptic
      transmission, and memory performance. However, the detailed mechanism linking
      disrupted mitochondrial metabolism and synaptic transmission is still
      uncharacterized. CB1 receptors are among the most abundant G protein-coupled
      receptors in the brain and impact on several processes, including fear coping,
      anxiety, stress, learning, and memory. Mitochondria perform several key
      physiological processes for neuronal homeostasis, including production of ATP and
      reactive oxygen species, calcium buffering, metabolism of neurotransmitters, and
      apoptosis. It is therefore possible that acute activation of mtCB1 impacts on
      these different mitochondrial functions to modulate synaptic transmission. In
      reviewing and integrating across the literature in this area, we describe the
      possible mechanisms involved in the regulation of brain physiology by mtCB1
      receptors.

PMID- 29058340
TI  - Molecular typing and occurrence of beta-lactam resistance genes of Shigella
      sonnei strains isolated from 1983 to 2014 in the Sao Paulo state of Brazil.
AB  - Shigella sonnei, which has generally been associated with dysentery in developed
      countries, has recently been emerging in developing countries. Specifically, in
      Brazil few published studies have that molecularly characterized this species.
      The aims of this study were to analyze the efficacy of typing using multiple
      locus variable-number tandem-repeat analysis (MLVA), study the phylogeny by multi
      locus sequence typing (MLST) and assess the presence of some beta-lactam
      resistance genes in S. sonnei strains isolated from human diarrhoeic faeces in
      the Sao Paulo State in Brazil between 1983 and 2014. Seventy-two such S. sonnei
      strains were typed by MLVA and grouped into two clusters. The discrimination
      index of MLVA was found to be 0.996. Twenty strains were typed by MLST as ST152.
      In addition, the blaTEM gene was detected in eight (72.7%) of the 11 S. sonnei
      strains that had previously been shown to be resistant to beta-lactams. However,
      blaCTX-M-1group , blaCTX-M-9group and blaSHV genes were not found. MLVA results
      suggested the existence of two prevalent subtypes in the S. sonnei strains
      studied, confirming previous results. Moreover, MLVA efficiently discriminated
      monomorphic S. sonnei species. Because the S. sonnei strains studied belonged to
      clonal complex 152 and all isolates were typed as ST152, MLST is not a suitable
      method for studying the population structure of S. sonnei. Although, the rates of
      beta-lactam resistance were not high in the present study, the frequency of
      blaTEM may represent a risk for patients receiving antimicrobial treatment. Taken
      together, the results provide better molecular characterization of this globally
      clinically important pathogen.

PMID- 29058341
TI  - Multichannel wearable fNIRS-EEG system for long-term clinical monitoring.
AB  - Continuous brain imaging techniques can be beneficial for the monitoring of
      neurological pathologies (such as epilepsy or stroke) and neuroimaging protocols
      involving movement. Among existing ones, functional near-infrared spectroscopy
      (fNIRS) and electroencephalography (EEG) have the advantage of being noninvasive,
      nonobstructive, inexpensive, yield portable solutions, and offer complementary
      monitoring of electrical and local hemodynamic activities. This article presents
      a novel system with 128 fNIRS channels and 32 EEG channels with the potential to
      cover a larger fraction of the adult superficial cortex than earlier works, is
      integrated with 32 EEG channels, is light and battery-powered to improve
      portability, and can transmit data wirelessly to an interface for real-time
      display of electrical and hemodynamic activities. A novel fNIRS-EEG stretchable
      cap, two analog channels for auxiliary data (e.g., electrocardiogram), eight
      digital triggers for event-related protocols and an internal accelerometer for
      movement artifacts removal contribute to improve data acquisition quality. The
      system can run continuously for 24 h. Following instrumentation validation and
      reliability on a solid phantom, performance was evaluated on (1) 12 healthy
      participants during either a visual (checkerboard) task at rest or while
      pedalling on a stationary bicycle or a cognitive (language) task and (2) 4
      patients admitted either to the epilepsy (n = 3) or stroke (n = 1) units. Data
      analysis confirmed expected hemodynamic variations during validation recordings
      and useful clinical information during in-hospital testing. To the best of our
      knowledge, this is the first demonstration of a wearable wireless multichannel
      fNIRS-EEG monitoring system in patients with neurological conditions. Hum Brain
      Mapp 39:7-23, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29058342
TI  - Radiation-induced brain structural and functional abnormalities in presymptomatic
      phase and outcome prediction.
AB  - Radiation therapy, a major method of treatment for brain cancer, may cause severe
      brain injuries after many years. We used a rare and unique cohort of
      nasopharyngeal carcinoma patients with normal-appearing brains to study possible
      early irradiation injury in its presymptomatic phase before severe, irreversible
      necrosis happens. The aim is to detect any structural or functional imaging
      biomarker that is sensitive to early irradiation injury, and to understand the
      recovery and progression of irradiation injury that can shed light on outcome
      prediction for early clinical intervention. We found an acute increase in local
      brain activity that is followed by extensive reductions in such activity in the
      temporal lobe and significant loss of functional connectivity in a distributed,
      large-scale, high-level cognitive function-related brain network. Intriguingly,
      these radiosensitive functional alterations were found to be fully or partially
      recoverable. In contrast, progressive late disruptions to the integrity of the
      related far-end white matter structure began to be significant after one year.
      Importantly, early increased local brain functional activity was predictive of
      severe later temporal lobe necrosis. Based on these findings, we proposed a
      dynamic, multifactorial model for radiation injury and another preventive model
      for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29058344
TI  - Identifying Variability in Patient Characteristics and Prevalence of Emergency
      Department Utilization for Mental Health Diagnoses in Rural and Urban
      Communities.
AB  - PURPOSE: In order to redirect at-risk patients to more appropriate, cost
      effective behavioral health care, research must identify the prevalence, and
      common characteristics, of patients presenting to the emergency department (ED)
      for mental disorders. QUESTION: Are large, small, and/or isolated rural patients
      presenting to the ED for mental disorders in greater proportion than urban ED
      patients? METHODS: Analyses included data from the Health Care Cost and
      Utilization Project State Emergency Department Databases (2013) provided by 7
      states, covering all Census regions. Variables included patient demographics, ZIP
      code, and primary and secondary ED diagnoses. ZIP codes were linked to the Rural
      Urban Commuting Areas, aggregating into 4 categories. Prevalence rates were
      compared within and between groups (P < .05). FINDINGS: Nearly 1 in 20 ED visits
      carried a primary/secondary diagnosis of mental disorder. Large, small, and
      isolated rural patients were not more likely than urban patients to present to
      the ED for mental disorders. Large, small, and isolated rural residents diagnosed
      with a primary/secondary mental disorder in the ED were more likely than urban to
      be female, 65 years of age or older, covered by Medicaid or Medicare, and dual
      eligible. The top 3 diagnoses for mental disorders in the ED were anxiety-state,
      unspecified; depressive disorder; and suicidal ideation. CONCLUSIONS: EDs
      treating large, small, or isolated rural patients with mental disorders are more
      likely to treat populations identified in the literature at greater risk of
      preventable visits, readmitting, and more costly care. Recommendations are made
      for policy, community interventions, workforce, and training.

PMID- 29058343
TI  - GenoType(r) HelicoDR test in comparison with histology and culture for
      Helicobacter pylori detection and identification of resistance mutations to
      clarithromycin and fluoroquinolones.
AB  - BACKGROUND: There are several methods for Helicobacter pylori infection
      diagnosis. AIM: The efficacies of three methods for H. pylori identification
      directly from a biopsy were compared: histology, culture, and molecular
      GenoType(r) HelicoDR test. MATERIALS & METHODS: Eighty-five triplicates of
      stomach antrum biopsies were obtained during gastroscopy procedures for culture,
      histology, and molecular assay. In addition, we performed molecular
      identification of genes encoding resistance to clarithromycin and
      fluoroquinolones. RESULTS: The results have shown that the most specific method
      with the highest number of positive specimens was by molecular kit, compared to
      culture and histology (94.3%, 77.1%, and 71.4%, respectively). There was a higher
      rate of resistance mutations to clarithromycin than to fluoroquinolones (68.26%
      vs 20%). The most common mutations for clarithromycin and fluoroquinolones
      resistance were found in alleles A2143G and N87K, respectively. The highest rate
      of positive specimens was identified by the molecular. DISCUSSION: GenoType
      HelicoDR kit (94.3%), which has several advantages: direct identification, strain
      resistance characterization, mixture of genotypes detection, and no transport or
      storage limitations; thus, it is an excellent epidemiological screening tool.
      This work has demonstrated a lower resistance rate to fluoroquinolones; it is
      possible that in the investigated geographic area treatment with fluoroquinolones
      may be preferable to clarithromycin. GenoType(r) HelicoDR test eliminates the
      need for culture performance and susceptibility tests for several common
      antibiotic agents and enables optimal and specific antibiotic treatment
      adjustment. CONCLUSION: We recommend a combination of PCR assay and bacterial
      culture for a quick method of screening and more efficient identification of H.
      pylori strains and resistance patterns.

PMID- 29058345
TI  - Recent Advances in Functional Polymer Decorated Two-Dimensional Transition-Metal
      Dichalcogenides Nanomaterials for Chemo-Photothermal Therapy.
AB  - Novel nanomaterials and advanced nanotechnologies continue to promote the fast
      development of new approaches for efficient tumor therapy. As an alternative
      choice to various traditional therapies, non-invasive photothermal therapy (PTT)
      has attracted significant attention mainly due to its low cost, highly
      localizing, specific tumor treatment and minimal side effects on healthy tissues.
      PTT induced by photo-absorbing agents which can absorb and convert the external
      NIR laser into heat to ablate tumors. Plenty of studies have shown the
      significant potential of PTT to treat tumors in future practical applications.
      However, PTT alone usually could not eradicate tumors considering the intensity
      of laser gradual attenuates in biological tissues and the heat generated tends to
      distribute inhomogeneous within tumors tissues. Combination of chemotherapy with
      photothermal therapy into one system for tumor therapy is an effective strategy
      to further improve the therapy efficiency. In this Minireview, we focus on the
      recent advances in constructing PTT therapeutic and multi-model combination
      therapeutic via integrating nanomaterials and functional polymers.

PMID- 29058347
TI  - Nacre-Inspired Structural Composites: Performance-Enhancement Strategy and
      Perspective.
AB  - For modern material engineering, one of the most ambitious goals is to develop
      lightweight structural materials with superior strength and toughness. Nacre, a
      typical biomaterial with high mechanical performance, has always inspired
      synthesis of high-performance structural composites. Here, the synthesis
      strategies for further enhancing the strength and toughness of novel nacre
      inspired structural composites, including ternary artificial nacre, artificial
      nacre reinforced by bridges, and those with an ultrahigh content of a hard phase,
      are reviewed. Also, the challenges and outlook for preparing lighter, stronger,
      and tougher structural composites are discussed.

PMID- 29058346
TI  - Highly Efficient and Stable Water-Oxidation Electrocatalysis with a Very Low
      Overpotential using FeNiP Substitutional-Solid-Solution Nanoplate Arrays.
AB  - The development of efficient water-oxidation electrocatalysts based on
      inexpensive and earth-abundant materials is significant to enable water splitting
      as a future renewable energy source. Herein, the synthesis of novel FeNiP solid
      solution nanoplate (FeNiP-NP) arrays and their use as an active catalyst for high
      performance water-oxidation catalysis are reported. The as-prepared FeNiP-NP
      catalyst on a 3D nickel foam substrate exhibits excellent electrochemical
      performance with a very low overpotential of only 180 mV to reach a current
      density of 10 mA cm-2 and an onset overpotential of 120 mV in 1.0 m KOH for the
      oxygen evolution reaction (OER). The slope of the Tafel plot is as low as 76.0 mV
      dec-1 . Furthermore, the long-term electrochemical stability of the FeNiP-NP
      electrode is investigated by cyclic voltammetry (CV) at 1.10-1.55 V versus
      reversible hydrogen electrode (RHE), demonstrating very stable performance with
      negligible loss in activity after 1000 CV cycles. This present FeNiP-NP solid
      solution is thought to represent the best OER catalytic activity among the non
      noble metal catalysts reported so far.

PMID- 29058348
TI  - Functional rhythmogenic domains defined by astrocytic networks in the trigeminal
      main sensory nucleus.
AB  - Stimuli that induce rhythmic firing in trigeminal neurons also increase
      astrocytic coupling and reveal networks that define the boundaries of this
      particular population. Rhythmic firing depends on astrocytic coupling which in
      turn depends on S100beta. In many nervous functions that rely on the ability of
      neuronal networks to generate a rhythmic pattern of activity, coordination of
      firing is an essential feature. Astrocytes play an important role in some of
      these networks, but the contribution of astrocytic coupling remains poorly
      defined. Here we investigate the modulation and organization of astrocytic
      networks in the dorsal part of the trigeminal main sensory nucleus (NVsnpr),
      which forms part of the network generating chewing movements. Using whole-cell
      recordings and the dye coupling approach by filling a single astrocyte with
      biocytin to reveal astrocytic networks, we showed that coupling is limited under
      resting conditions, but increases importantly under conditions that induce
      rhythmic firing in NVsnpr neurons. These are: repetitive electrical stimulation
      of the sensory inputs to the nucleus, local application of NMDA and decrease of
      extracellular Ca2+ . We have previously shown that rhythmic firing induced in
      NVsnpr neurons by these stimuli depends on astrocytes and their Ca2+ -binding
      protein S100beta. Here we show that extracellular blockade of S100beta also
      prevents the increase in astrocytic coupling induced by local application of
      NMDA. Most of the networks were small and remained confined to the functionally
      distinct area of dorsal NVsnpr. Disrupting coupling by perfusion with the
      nonspecific gap junction blocker, carbenoxolone or with GAP26, a selective
      inhibitor of connexin 43, mostly expressed in astrocytes, abolished NMDA-induced
      rhythmic firing in NVsnpr neurons. These results suggest that astrocytic coupling
      is regulated by sensory inputs, necessary for neuronal bursting, and organized in
      a region specific manner.

PMID- 29058349
TI  - The bumps under the hippocampus.
AB  - Shown in every neuroanatomy textbook, a key morphological feature is the bumpy
      ridges, which we refer to as hippocampal dentation, on the inferior aspect of the
      hippocampus. Like the folding of the cerebral cortex, hippocampal dentation
      allows for greater surface area in a confined space. However, examining numerous
      approaches to hippocampal segmentation and morphology analysis, virtually all
      published 3D renderings of the hippocampus show the inferior surface to be quite
      smooth or mildly irregular; we have rarely seen the characteristic bumpy
      structure on reconstructed 3D surfaces. The only exception is a 9.4T postmortem
      study (Yushkevich et al. [2009]: NeuroImage 44:385-398). An apparent question is,
      does this indicate that this specific morphological signature can only be
      captured using ultra high-resolution techniques? Or, is such information buried
      in the data we commonly acquire, awaiting a computation technique that can
      extract and render it clearly? In this study, we propose an automatic and robust
      super-resolution technique that captures the fine scale morphometric features of
      the hippocampus based on common 3T MR images. The method is validated on 9.4T
      ultra-high field images and then applied on 3T data sets. This method opens
      possibilities of future research on the hippocampus and other sub-cortical
      structural morphometry correlating the degree of dentation with a range of
      diseases including epilepsy, Alzheimer's disease, and schizophrenia. Hum Brain
      Mapp 39:472-490, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29058350
TI  - Synthesis of Large-Size 1T' ReS2x Se2(1-x) Alloy Monolayer with Tunable Bandgap
      and Carrier Type.
AB  - Chemical vapor deposition growth of 1T' ReS2x Se2(1-x) alloy monolayers is
      reported for the first time. The composition and the corresponding bandgap of the
      alloy can be continuously tuned from ReSe2 (1.32 eV) to ReS2 (1.62 eV) by
      precisely controlling the growth conditions. Atomic-resolution scanning
      transmission electron microscopy reveals an interesting local atomic distribution
      in ReS2x Se2(1-x) alloy, where S and Se atoms are selectively occupied at
      different X sites in each Re-X6 octahedral unit cell with perfect matching
      between their atomic radius and space size of each X site. This structure is much
      attractive as it can induce the generation of highly desired localized electronic
      states in the 2D surface. The carrier type, threshold voltage, and carrier
      mobility of the alloy-based field effect transistors can be systematically
      modulated by tuning the alloy composition. Especially, for the first time the
      fully tunable conductivity of ReS2x Se2(1-x) alloys from n-type to bipolar and p
      type is realized. Owing to the 1T' structure of ReS2x Se2(1-x) alloys, they
      exhibit strong anisotropic optical, electrical, and photoelectric properties. The
      controllable growth of monolayer ReS2x Se2(1-x) alloy with tunable bandgaps and
      electrical properties as well as superior anisotropic feature provides the
      feasibility for designing multifunctional 2D optoelectronic devices.

PMID- 29058351
TI  - Health and Well-Being Among Young People From Canadian Farms: Associations With a
      Culture of Risk-Taking.
AB  - PURPOSE: To determine whether patterns of adolescent risk behavior in rural
      populations, and especially farm populations, are associated with negative
      indicators of adolescent health and well-being, beyond an established association
      between risk-taking and injury. METHODS: The study base was Cycle 7 (2014) of the
      Canadian Health Behaviour in School-Aged Children study. Children aged 11-16
      years (n = 2,565; 2,533 weighted) who reported living or working on farms were
      matched within schools in a 1:1 ratio with other rural children. We related a
      scale describing engagement in multiple risk behavior to a series of indicators
      of adolescent health and well-being. FINDINGS: Farm children, particularly male
      farm children, showed the highest levels of risk behavior. Multiple risk behavior
      was strongly and consistently associated with negative indicators of general
      health, mental health (life satisfaction, psychosomatic symptoms), and academic
      performance in all subpopulations. CONCLUSIONS: Adolescent risk behavior in rural
      populations, and especially farm populations, is common and associated with a
      variety of negative indicators of adolescent health and well-being. We speculate
      that the origins of this risk-taking lifestyle surround cultural definitions of
      self and identity, which have both protective and negative effects.

PMID- 29058352
TI  - Affective creativity meets classic creativity in the scanner.
AB  - The investigation of neurocognitive processes underlying more real-life creative
      behavior is among the greatest challenges in creativity research. In this fMRI
      study, we addressed this issue by investigating functional patterns of brain
      activity while participants were required to be creative in an affective context.
      Affective creativity was assessed in terms of individual's inventiveness in
      generating alternative appraisals for anger-evoking events, which has recently
      emerged as a new ability concept in cognitive reappraisal research. In addition,
      a classic divergent thinking task was administered. Both creativity tasks yielded
      strong activation in left prefrontal regions, indicating their shared cognitive
      processing demands like the inhibition of prepotent responses, shifting between
      different perspectives and controlled memory retrieval. Regarding task-specific
      differences, classic creative ideation activated a characteristic divergent
      thinking network comprising the left supramarginal, inferior temporal, and
      inferior frontal gyri. Affective creativity on the other hand specifically
      recruited the right superior frontal gyrus, presumably involved in the
      postretrieval monitoring of reappraisal success, and core hubs of the default
      mode network, which are also implicated in social cognition. As a whole, by
      taking creativity research to the realm of emotion, this study advances our
      understanding of how more real-life creativity is rooted in the brain. Hum Brain
      Mapp 39:393-406, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29058353
TI  - Fast Ca2+ responses in astrocyte end-feet and neurovascular coupling in mice.
AB  - Cerebral blood flow (CBF) is regulated by the activity of neurons and astrocytes.
      Understanding how these cells control activity-dependent increases in CBF is
      crucial to interpreting functional neuroimaging signals. The relative importance
      of neurons and astrocytes is debated, as are the functional implications of fast
      Ca2+ changes in astrocytes versus neurons. Here, we used two-photon microscopy to
      assess Ca2+ changes in neuropil, astrocyte processes, and astrocyte end-feet in
      response to whisker pad stimulation in mice. We also developed a pixel-based
      analysis to improve the detection of rapid Ca2+ signals in the subcellular
      compartments of astrocytes. Fast Ca2+ responses were observed using both chemical
      and genetically encoded Ca2+ indicators in astrocyte end-feet prior to dilation
      of arterioles and capillaries. A low dose of the NMDA receptor antagonist
      (5R,10s)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine
      hydrogen-maleate (MK801) attenuated fast Ca2+ responses in the neuropil and
      astrocyte processes, but not in astrocyte end-feet, and the evoked CBF response
      was preserved. In addition, a low dose of 4,5,6,7-tetrahydroisoxazolo[5,4
      c]pyridin-3-ol (THIP), an agonist for the extrasynaptic GABAA receptor (GABAA R),
      increased CBF responses and the fast Ca2+ response in astrocyte end-feet but did
      not affect Ca2+ responses in astrocyte processes and neuropil. These results
      suggest that fast Ca2+ increases in the neuropil and astrocyte processes are not
      necessary for an evoked CBF response. In contrast, as local fast Ca2+ responses
      in astrocyte end-feet are unaffected by MK801 but increase via GABAA R-dependent
      mechanisms that also increased CBF responses, we hypothesize that the fast Ca2+
      increases in end-feet adjust CBF during synaptic activity.

PMID- 29058354
TI  - The practice of diagnosing and reporting transfusion-associated circulatory
      overload: a national survey among physicians and haemovigilance officers.
AB  - OBJECTIVES: This study aims at identifying factors that disciplines consider when
      diagnosing and reporting transfusion-associated circulatory overload ('TACO').
      BACKGROUND: TACO is a clinical diagnosis based mainly on subjective factors.
      Therefore, TACO could be an underreported complication of blood transfusion.
      METHODS: A survey was conducted among critical care physicians,
      anaesthesiologists, haematologists, transfusion medicine physicians and
      haemovigilance officers using case vignettes and a questionnaire. Factors that
      may affect diagnosing TACO were investigated using conjoint analysis. A positive
      B-coefficient indicates a positive preference for diagnosing TACO. Participants
      rated factors influencing reporting TACO on a 0- to 100-point scale. RESULTS: One
      hundred and seven surveys were returned (62%). Vignettes showed preferences in
      favour of diagnosing TACO with the onset of symptoms within 2 h [beta 0.4(-0.1
      1.0)], positive fluid balance [beta 0.9(0.4-1.5)] and history of renal failure
      [beta 0.6(0.1-1.2)]. Compared with transfusion of a single unit of red blood
      cells (RBC), respondents showed a preference for diagnosing TACO following a
      single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate
      (PPC) [beta 0.3(-0.2-0.7) resp. 0.5(-0.1-1.2)]. Multiple transfusion (6 RBC + 4
      S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1
      S/D plasma [beta 0.3(-0.8-1.3)]. Respondents did not fully take into account new
      hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60
      (IQR 50-80)]. No differences were observed between disciplines involved.
      CONCLUSION: When diagnosing and reporting TACO, physicians and haemovigilance
      officers do consider known risk factors for TACO. Reporting could be improved by
      increasing the awareness of haemodynamic variables in future education
      programmes.

PMID- 29058355
TI  - Functional subdivisions within the human intraparietal sulcus are involved in
      visuospatial transformation in a non-context-dependent manner.
AB  - Object-based visuospatial transformation is important for the ability to interact
      with the world and the people and objects within it. In this preliminary
      investigation, we hypothesized that object-based visuospatial transformation is a
      unitary process invoked regardless of current context and is localized to the
      intraparietal sulcus. Participants (n = 14) performed both antisaccade and mental
      rotation tasks while scanned using fMRI. A statistical conjunction confirmed that
      both tasks activated the intraparietal sulcus. Statistical parametric anatomical
      mapping determined that the statistical conjunction was localized to
      intraparietal sulcus subregions hIP2 and hIP3. A Gaussian naive Bayes classifier
      confirmed that the conjunction in region hIP3 was indistinguishable between
      tasks. The results provide evidence that object-based visuospatial transformation
      is a domain-general process that is invoked regardless of current context. Our
      results are consistent with the modular model of the posterior parietal cortex
      and the distinct cytoarchitectonic, structural, and functional connectivity
      profiles of the subregions in the intraparietal sulcus. Hum Brain Mapp 39:354
      368, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29058356
TI  - Predicting auditory feedback control of speech production from subregional shape
      of subcortical structures.
AB  - Although a growing body of research has focused on the cortical sensorimotor
      mechanisms that support auditory feedback control of speech production, much less
      is known about the subcortical contributions to this control process. This study
      examined whether subregional anatomy of subcortical structures assessed by
      statistical shape analysis is associated with vocal compensations and cortical
      event-related potentials in response to pitch feedback errors. The results
      revealed significant negative correlations between the magnitudes of vocal
      compensations and subregional shape of the right thalamus, between the latencies
      of vocal compensations and subregional shape of the left caudate and pallidum,
      and between the latencies of cortical N1 responses and subregional shape of the
      left putamen. These associations indicate that smaller local volumes of the basal
      ganglia and thalamus are predictive of slower and larger neurobehavioral
      responses to vocal pitch errors. Furthermore, increased local volumes of the left
      hippocampus and right amygdala were predictive of larger vocal compensations,
      suggesting that there is an interplay between the memory-related subcortical
      structures and auditory-vocal integration. These results, for the first time,
      provide evidence for differential associations of subregional morphology of the
      basal ganglia, thalamus, hippocampus, and amygdala with neurobehavioral
      processing of vocal pitch errors, suggesting that subregional shape measures of
      subcortical structures can predict behavioral outcome of auditory-vocal
      integration and associated neural features. Hum Brain Mapp 39:459-471, 2018. (c)
      2017 Wiley Periodicals, Inc.

PMID- 29058357
TI  - Identifying disease foci from static and dynamic effective connectivity networks:
      Illustration in soldiers with trauma.
AB  - Brain connectivity studies report group differences in pairwise connection
      strengths. While informative, such results are difficult to interpret since our
      understanding of the brain relies on region-based properties, rather than on
      connection information. Given that large disruptions in the brain are often
      caused by a few pivotal sources, we propose a novel framework to identify the
      sources of functional disruption from effective connectivity networks. Our
      approach integrates static and time-varying effective connectivity modeling in a
      probabilistic framework, to identify aberrant foci and the corresponding aberrant
      connectomics network. Using resting-state fMRI, we illustrate the utility of this
      novel approach in U.S. Army soldiers (N = 87) with posttraumatic stress disorder
      (PTSD), mild traumatic brain injury (mTBI) and combat controls. Additionally, we
      employed machine-learning classification to identify those significant
      connectivity features that possessed high predictive ability. We identified three
      disrupted foci (middle frontal gyrus [MFG], insula, hippocampus), and an aberrant
      prefrontal-subcortical-parietal network of information flow. We found the MFG to
      be the pivotal focus of network disruption, with aberrant strength and temporal
      variability of effective connectivity to the insula, amygdala and hippocampus.
      These connectivities also possessed high predictive ability (giving a
      classification accuracy of 81%); and they exhibited significant associations with
      symptom severity and neurocognitive functioning. In summary, dysregulation
      originating in the MFG caused elevated and temporally less-variable connectivity
      in subcortical regions, followed by a similar effect on parietal memory-related
      regions. This mechanism likely contributes to the reduced control over traumatic
      memories leading to re-experiencing, hyperarousal and flashbacks observed in
      soldiers with PTSD and mTBI. Hum Brain Mapp 39:264-287, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29058359
TI  - High-Performance Nanocomposites Inspired by Nature.
AB  - Natural materials, including nacre, bone, and the lobster cuticle, exhibit
      excellent mechanical properties, combining high strength and toughness. Such
      materials have the added benefit of being light in weight. These advantageous
      features are due to such natural materials' orderly hierarchical architectures
      and abundant interface interactions. How to utilize these design principles
      created by nature to fabricate high-performance bioinspired nanocomposites
      remains a great research challenge. A logical roadmap for developing these
      nanocomposites can be described as "discovery, invention, and creation." Here,
      the discovery of the relationship between natural materials' design principles
      and such materials' extraordinary mechanical properties is discussed. Then, the
      invention of bioinspired strategies for mimicking natural materials is considered
      and representative strategies addressed. Next, the creation of multifunctional
      nanocomposites is discussed and bioinspired nanocomposites, including fiber
      nanocomposites, 2D film nanocomposites, and 3D bulk nanocomposites reviewed.
      Finally, a perspective and outlook for future directions in making bioinspired
      nanocomposites is provided to offer inspiration to the community and a clear
      vision for future research.

PMID- 29058358
TI  - An investigation of regional cerebral blood flow and tissue structure changes
      after acute administration of antipsychotics in healthy male volunteers.
AB  - Chronic administration of antipsychotic drugs has been linked to structural brain
      changes observed in patients with schizophrenia. Recent MRI studies have shown
      rapid changes in regional brain volume following just a single dose of these
      drugs. However, it is not clear if these changes represent real volume changes or
      are artefacts ("apparent" volume changes) due to drug-induced physiological
      changes, such as increased cerebral blood flow (CBF). To address this, we
      examined the effects of a single, clinical dose of three commonly prescribed
      antipsychotics on quantitative measures of T1 and regional blood flow of the
      healthy human brain. Males (n = 42) were randomly assigned to one of two parallel
      groups in a double-blind, placebo-controlled, randomized, three-period cross-over
      study design. One group received a single oral dose of either 0.5 or 2 mg of
      risperidone or placebo during each visit. The other received olanzapine (7.5 mg),
      haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1
      weighted images were acquired at the estimated peak plasma concentration of the
      drug. All three drugs caused localized increases in striatal blood flow, although
      drug and region specific effects were also apparent. In contrast, all assessments
      of T1 and brain volume remained stable across sessions, even in those areas
      experiencing large changes in CBF. This illustrates that a single clinically
      relevant oral dose of an antipsychotic has no detectable acute effect on T1 in
      healthy volunteers. We further provide a methodology for applying quantitative
      imaging methods to assess the acute effects of other compounds on structural MRI
      metrics. Hum Brain Mapp 39:319-331, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29058360
TI  - Design of a New Small-Molecule Electron Acceptor Enables Efficient Polymer Solar
      Cells with High Fill Factor.
AB  - Improving the fill factor (FF) is known as a challenging issue in organic solar
      cells (OSCs). Herein, a strategy of extending the conjugated area of end-group is
      proposed for the molecular design of acceptor-donor-acceptor (A-D-A)-type small
      molecule acceptor (SMA), and an indaceno[1,2-b:5,6-b']dithiophene-based SMA,
      namely IDTN, by end-capping with the naphthyl fused 2-(3
      oxocyclopentylidene)malononitrile is synthesized. Benefiting from the pi
      conjugation extension by fusing two phenyls, IDTN shows stronger molecular
      aggregation, more ordered packing structure, thus over one order of magnitude
      higher electron mobility relative to its counterpart. By utilizing the
      fluorinated polymer (PBDB-TF) as the electron donor, the corresponding device
      exhibits a high efficiency of 12.2% with a record-high FF of 0.78, which is
      approaching the theoretical limit of OSCs. Compared with the reference molecule,
      such a high FF in the IDTN system can be mainly attributed to the more ordered pi
      pi packing of acceptor aggregates, higher domain purity and symmetric carrier
      transport in the blend. Hence, enlarging the conjugated area of the terminal
      group in these A-D-A-type SMAs is a promising approach not only for enhancing the
      electron mobility, but also for improving the blend morphology, and both of them
      are conducive to the fill-factor breakthrough.

PMID- 29058361
TI  - Pain Remission at One-Year Follow-Up With Spinal Cord Stimulation.
AB  - OBJECTIVES: Spinal Cord Stimulation (SCS) is an effective treatment for chronic
      pain. How often pain remission follows SCS has not been evaluated. This is a
      retrospective analysis of patients who underwent an implantation of spinal cord
      stimulators for various chronic pain conditions. The objective of the study was
      to elucidate characteristics and features of patients with pain relief greater
      than 80% after one year of treatment. METHODS: A total of 86 patients with
      thoracic SCS and 12-month follow-up data were identified. Patients were divided
      into a remission group (>80% improvement in Numeric Pain Rating Scale [NRS] pain
      scale), average responders (20-80% improvement) and a non-responder group (less
      than 20% improvement). These patient groups were compared via the following
      outcome measures: NRS, Oswestry Disability Index (ODI), Pain Catastrophizing
      Scale (PCS), McGill Pain Questionnaire (MPQ), and Insomnia Severity Index (ISI).
      Correlations with age, body mass index (BMI), tobacco and alcohol usage, patient
      satisfaction with SCS, disability status, and opioid usage were assessed.
      RESULTS: Nineteen of 86 patients (22%) were remitters at one year follow-up,
      including 17 patients who had an NRS = 0 at that time. Upon analyzing the three
      patient groups (non-responders, average responders, and remitters), remitter
      patients showed the greatest change over the one-year post-operative period in
      ODI (F(2) = 8.101, p < 0.01) and PCS (F(2) = 7.607, p < 0.01). Moreover,
      remission was less likely when the patients were on disability prior to implant
      (chi2 (2) = 6.469, p < 0.05) and on opioids pre-operatively (chi2 (2) = 17.688, p
      < 0.01). CONCLUSIONS: Our study demonstrates a remission rate of 22% with SCS at
      one-year follow with a total of 19.8% of our total patient cohort having an NRS
      of 0. Greater decreases in PCS and ODI correlate with remission. Further, pre
      operative disability and opioid use correlate with lower likelihood of remission.

PMID- 29058362
TI  - The ketone body metabolite beta-hydroxybutyrate induces an antidepression
      associated ramification of microglia via HDACs inhibition-triggered Akt-small
      RhoGTPase activation.
AB  - Direct induction of macrophage ramification has been shown to promote an
      alternative (M2) polarization, suggesting that the ramified morphology may
      determine the function of immune cells. The ketone body metabolite beta
      hydroxybutyrate (BHB) elevated in conditions including fasting and low
      carbohydrate ketogenic diet (KD) can reduce neuroinflammation. However, how
      exactly BHB impacts microglia remains unclear. We report that BHB as well as its
      producing stimuli fasting and KD induced obvious ramifications of murine
      microglia in basal and inflammatory conditions in a reversible manner, and these
      ramifications were accompanied with microglial profile toward M2 polarization and
      phagocytosis. The protein kinase B (Akt)-small RhoGTPase axis was found to
      mediate the effect of BHB on microglial shape change, as (i) BHB activated the
      microglial small RhoGTPase (Rac1, Cdc42) and Akt; (ii) Akt and Rac1-Cdc42
      inhibition abolished the pro-ramification effect of BHB; (iii) Akt inhibition
      prevented the activation of Rac1-Cdc42 induced by BHB treatment. Incubation of
      microglia with other classical histone deacetylases (HDACs) inhibitors, but not G
      protein-coupled receptor 109a (GPR109a) activators, also induced microglial
      ramification and Akt activation, suggesting that the BHB-induced ramification of
      microglia may be triggered by HDACs inhibition. Functionally, Akt inhibition was
      found to abrogate the effects of BHB on microglial polarization and phagocytosis.
      In neuroinflammatory models induced by lipopolysaccharide (LPS) or chronic
      unpredictable stress (CUS), BHB prevented the microglial process retraction and
      depressive-like behaviors, and these effects were abolished by Akt inhibition.
      Our findings for the first time showed that BHB exerts anti-inflammatory actions
      via promotion of microglial ramification.

PMID- 29058363
TI  - Minimally invasive esophagectomy in the lateral-prone position: Experience of 124
      cases in a single center.
AB  - BACKGROUND: Minimally invasive esophagectomy was first introduced as a new
      technique for esophageal cancer treatment 20 years ago. Performing this procedure
      in the lateral-prone position is the most appropriate method. Since May 2013, our
      center has performed 124 esophageal cancer operations using this procedure.
      Herein, we share our experience. METHODS: We retrospectively reviewed 124
      consecutive patients who had received minimally invasive esophagectomy in the
      lateral-prone position from May 2013 to June 2017. The procedure, operative
      variables, postoperative complications, and oncology outcomes were assessed.
      RESULTS: The surgery was successful in all 124 patients; three cases converted to
      an abdominal opening procedure during surgery. The mean total lymph node harvest
      was 19.2: 12.9 in the thoracic cavity and 6.0 in the abdominal cavity. The
      average total operation duration was 376 minutes and blood loss was 156 mL. No
      mortality occurred within 30 postoperative days. Forty-three cases of
      postoperative morbidity occurred in 38 patients (30.6%), including 11 anastomotic
      leakages (8.9%), 1 chyle leak (0.8%), 12 lateral recurrent nerve palsies (9.7%),
      11 pulmonary complications (8.9%), and 8 other complications (6.5%). A learning
      curve indicated that blood loss, operation duration, and the number of lymph
      nodes harvested would improve with time. CONCLUSIONS: Surgical and oncological
      outcomes following minimally invasive esophagectomy for esophageal cancer were
      acceptable. There are some advantages to this technique compared to previous
      reports of opening procedures.

PMID- 29058364
TI  - Enhanced red emission from BaMoO4 : Eu3+ by Bi3+ co-doping.
AB  - A series of Bi3+ ,Eu3+ -doped BaMoO4 phosphors was synthesized using a
      hydrothermal method. The crystal structure, morphology and optical properties of
      the phosphors were studied using X-ray diffraction (XRD), scanning electron
      microscope (SEM) and photoluminescence (PL) measurements. Three different
      particle morphologies were detected in the SEM observation. The energy dispersive
      spectroscopy (EDS) results indicated that the solubility of Bi3+ in spherical or
      rugby-like BaMoO4 particles was very low and the excess Bi3+ element was
      cumulated in the irregular particles. Characteristic emissions of Eu3+ ions (5 D0
      -> 7 FJ ; J = 0, 1, 2, 3, 4) were observed under excitation in ultraviolet (UV)
      light, with the most intense transition being the 5 D0  -> 7 F2 transition.
      Energy transfer from MoO42- and Bi3+ to Eu3+ can be readily achieved. Red
      emission intensity of Eu3+ was enhanced by a factor of two by co-doping with a
      small amount of Bi3+ . Optical properties as a function of Bi3+ content were
      studied and the optimum Bi3+ content in BaMoO4 nanocrystals was determined to be
      0.4 mol%.

PMID- 29058365
TI  - Spheroids Formation on Non-Adhesive Surfaces by Liquid Overlay Technique:
      Considerations and Practical Approaches.
AB  - Scalable and reproducible production of 3D cellular spheroids is highly demanded,
      by pharmaceutical companies, for drug screening purposes during the pre-clinical
      evaluation phase. These 3D cellular constructs, unlike the monolayer culture of
      cells, can mimic different features of human tissues, including cellular
      organization, cell-cell and cell-extracellular matrix (ECM) interactions. Up to
      now, different techniques (scaffold-based and -free) have been used for spheroids
      formation, being the Liquid Overlay Technique (LOT) one of the most explored
      methodologies, due to its low cost and easy handling. Additionally, during the
      last few decades, this technique has been widely investigated in order to enhance
      its potential for being applied in high-throughput analysis. Herein, an overview
      of the LOT advances, practical approaches, and troubleshooting is provided for
      those researchers that intend to produce spheroids using LOT, for drug screening
      purposes. Moreover, the advantages of the LOT over the other scaffold-free
      techniques used for the spheroids formation are also addressed. Highlights * 2D
      cell culture drawbacks are summarized; * spheroids mimic the features of human
      tissues; * scaffold-based and scaffold-free technologies for spheroids production
      are discussed; * advantages of LOT over other scaffold-free techniques are
      highlighted; * LOT advances, practical approaches and troubleshooting are
      underlined.

PMID- 29058366
TI  - Understanding LiOH Chemistry in a Ruthenium-Catalyzed Li-O2 Battery.
AB  - Non-aqueous Li-O2 batteries are promising for next-generation energy storage. New
      battery chemistries based on LiOH, rather than Li2 O2 , have been recently
      reported in systems with added water, one using a soluble additive LiI and the
      other using solid Ru catalysts. Here, the focus is on the mechanism of Ru
      catalyzed LiOH chemistry. Using nuclear magnetic resonance, operando
      electrochemical pressure measurements, and mass spectrometry, it is shown that on
      discharging LiOH forms via a 4 e- oxygen reduction reaction, the H in LiOH coming
      solely from added H2 O and the O from both O2 and H2 O. On charging, quantitative
      LiOH oxidation occurs at 3.1 V, with O being trapped in a form of dimethyl
      sulfone in the electrolyte. Compared to Li2 O2 , LiOH formation over Ru incurs
      few side reactions, a critical advantage for developing a long-lived battery. An
      optimized metal-catalyst-electrolyte couple needs to be sought that aids LiOH
      oxidation and is stable towards attack by hydroxyl radicals.

PMID- 29058367
TI  - CRISPR/Cas9-Based Counterselection Boosts Recombineering Efficiency in
      Pseudomonas putida.
AB  - While adoption of single-stranded DNA recombineering techniques has greatly eased
      genetic design of the platform strain Pseudomonas putida KT2440, available
      methods still produce the desired modifications/deletions at low frequencies.
      This makes isolation of mutants that do not display selectable or conspicuous
      phenotypes considerably difficult. To overcome this limitation, the authors have
      merged ssDNA recombineering with CRISPR/Cas9 technology in this bacterium for
      efficient killing of unmodified cells and thus non-phenotypic selection of
      bacteria bearing the mutations of interest. After incorporating the system into
      standardized pSEVA plasmids the authors tested its functional efficiency by
      targeting different types of changes that ranged from single nucleotide
      substitutions to one-gene deletions-to even the removal of the large flagellar
      cluster (~69 kb). Simultaneous introduction of two independent gene deletions was
      tested as well. In all cases, directing the crRNA/Cas9 complexes toward non
      modified, wild-type genomic sequences boosted dramatically the appearance of the
      mutants at stake in the absence of any phenotypic selection. The results
      presented here upgrade the engineering possibilities of the genome of this
      environmental bacterium (and possibly other Gram-negatives) to obtain
      modifications that are otherwise cumbersome to generate.

PMID- 29058368
TI  - Modified method for distinguishing the intersegmental border for lung
      segmentectomy.
AB  - This paper analyzed the results of a modified and simpler technique for
      distinguishing the intersegmental border during lung segmentectomy surgery. From
      January 2013 to December 2015, 539 patients with screening-detected lung nodules
      <2 cm in maximum diameter underwent anatomic segmentectomy. With the guidance of
      preoperative three-dimensional computed tomography bronchography and angiography,
      the bronchus, artery, and intrasegmental vein of the targeted segment could be
      precisely dissected under unilateral differential ventilation, and then
      intersegmental demarcation was confirmed by the modified inflation-deflation
      method. The demarcation presented by this method was highly coincident with the
      real intersegmental border. Dissection along the border between the collapsed and
      inflated segments using either electrocautery or staples was safe, with almost no
      air leak or bleeding. This technique is a simple and effective alternative to
      previously described intersegmental border marking methods.

PMID- 29058369
TI  - Association of the alcohol dehydrogenase gene polymorphism rs1789891 with gray
      matter brain volume, alcohol consumption, alcohol craving and relapse risk.
AB  - Alcohol metabolizing enzymes, such as the alcohol dehydrogenases and the aldehyde
      dehydrogenases, regulate the levels of acetaldehyde in the blood and play an
      important role in the development and maintenance of alcohol addiction. Recent
      genome-wide systematic searches found associations between a single nucleotide
      polymorphism (rs1789891, risk allele: A, protective allele: C) in the alcohol
      dehydrogenase gene cluster and the risk of alcohol dependence. The current study
      investigated the effect of this single nucleotide polymorphism on alcohol
      consumption, craving for alcohol, relapse risk and brain gray matter volume.
      Alcohol-dependent patients (n = 74) and controls (n = 43) were screened,
      genotyped and underwent magnetic resonance imaging scanning, and relapse data
      were collected during 3 months following the experiment. Alcohol-dependent A
      allele carriers reported increased alcohol craving and higher alcohol consumption
      compared with the group of alcohol-dependent individuals homozygous for the C
      allele, which displayed craving values similar to the control group. Further,
      follow-up data indicated that A allele carriers relapsed earlier to heavy
      drinking compared with individuals with two C alleles. Analyses of gray matter
      volume indicated a significant genotype difference in the patient group:
      individuals with two C alleles had reduced gray matter volume in the left and
      right superior, middle and inferior temporal gyri. Findings of the current study
      further support the relevance of genetic variants in alcohol metabolizing enzymes
      to addictive behavior, brain tissue volume and relapse risk. Genotype-dependent
      differences in acetaldehyde formation, implicated by earlier studies, might be
      the biological substrate of the genotype differences.

PMID- 29058370
TI  - Proton therapy for pediatric head and neck malignancies.
AB  - PURPOSE: Pediatric head and neck malignancies are managed with intensive
      multimodality therapy. Proton beam therapy (PBT) may reduce toxicity by limiting
      exposure of normal tissue to radiation. In this study, we report acute toxicities
      and early outcomes following PBT for pediatric head and neck malignancies.
      MATERIALS AND METHODS: Between 2010 and 2016, pediatric patients with
      nonhematologic malignancies of the head and neck were treated with PBT. Clinical
      and dosimetric data were abstracted from the medical record and treatment
      planning system with institutional review board approval. RESULTS: Sixty-nine
      consecutive pediatric patients were treated with proton-based radiotherapy for
      head and neck malignancies. Thirty-five were treated for rhabdomyosarcoma to a
      median dose of 50.4 Gy relative biological effectiveness [RBE]. Ten patients were
      treated for Ewing sarcoma to a median dose of 55.8 Gy[RBE]. Twenty-four patients
      were treated for other histologies to a median dose of 63.0 Gy[RBE]. Grade 3 oral
      mucositis, anorexia, and dysphagia were reported to be 4, 22, and 7%,
      respectively. Actuarial 1-year freedom from local recurrence was 92% (95% CI 80
      97). Actuarial 1-year overall survival was 93% (95% CI 79-98) in the entire
      cohort. Oral cavity mucositis was significantly correlated with oral cavity dose
      (D80 and D50 [P < 0.05], where D80 and D50 are dose to 50% of the volume and dose
      to 80% of the volume, respectively). CONCLUSIONS: In this study, we report low
      rates of acute toxicity in a cohort of pediatric patients with head and neck
      malignancies. PBT appears safe for this patient population, with local control
      rates similar to historical reports. Longer follow-up will be required to
      evaluate late toxicity and long-term disease control.

PMID- 29058371
TI  - Integrative review of cervical cancer screening in Western Asian and Middle
      Eastern Arab countries.
AB  - Population-based screening programs have resulted in minimizing mortality and
      morbidity from cervical cancer. The aim of this integrative review was to explore
      the factors influencing access of women from Western Asian and Middle Eastern
      Arab countries to cervical cancer screening. A systematic search for studies
      conducted in Arab countries in those regions, and published in English between
      January 2002 and January 2017, was undertaken. Thirteen papers were selected and
      subjected to quality appraisal. A three step analysis was used, which involved a
      summary of the evidence, analysis of both quantitative and qualitative data, and
      integration of the results in narrative form. Few population-based cervical
      cancer screening programs had been implemented in the relevant countries, with
      low knowledge of, and perceptions about, cervical screening among Arab women, the
      majority of whom are Muslim. Factors affecting the uptake of cervical cancer
      screening practices were the absence of organized, systematic programs, low
      screening knowledge among women, healthcare professionals' attitudes toward
      screening, pain and embarrassment, stigma, and sociocultural beliefs. Policy
      changes are urgently needed to promote population-based screening programs.
      Future research should address the promotion of culturally-sensitive strategies
      to enable better access of Arab Muslim women to cervical cancer screening.

PMID- 29058372
TI  - Minimal residual disease in multiple myeloma: Benefits of flow cytometry.
AB  - Over the last 20 years, the approaches to the treatment of multiple myeloma (MM)
      have changed considerably, which led to an increase in remission rate. Using new
      diagnostic methods has made it possible to assess the response to treatment more
      reliably and forecast disease recurrence: allele-specific polymerase chain
      reaction, new-generation sequencing and multicolor flow cytometry enable minimal
      residual disease (MRD) detection of with sensitivity of 10-5 to 10-6 . MRD
      assessment with flow cytometry using is a rapidly developing area of research.
      The goal of multicenter groups that use flow cytometry as a tool to detect MRD in
      patients with MM is achieving standardization and increasing sensitivity and
      specificity of this method. This article provides data about the methods used for
      MRD monitoring and describes the advances in the field of flow cytometry.

PMID- 29058373
TI  - Impact on major CBC parameters caused by different types of lipids in patient
      plasma.

PMID- 29058374
TI  - Magnetic Separation on a New Level: Characterization and Performance Prediction
      of a cGMP Compliant "Rotor-Stator" High-Gradient Magnetic Separator.
AB  - The growing market of biopharmaceuticals and the constant developments in
      upstream fermentation have generated a strong demand for new downstream
      purification methods. Magnetic separation in combination with functional magnetic
      particles has been known for many years as a promising candidate for a direct
      capturing tool in protein purification but the lack of suitable GMP-compliant
      purification equipment has prevented the launch of this technology in large scale
      bioprocessing. To tackle this bottle-neck, the principle of a "rotor-stator" high
      gradient magnetic separator is fully redesigned to meet the rigorous requirements
      of modern cGMP biotechnology purification processes. In order to fulfill
      regulatory requirements, the separation chamber is reengineered to allow
      effective cleaning and sterilization in place while maintaining excellent
      separation capacities and efficiencies. Two kinds of commercially available
      magnetic particles are used to validate key performance data and determine system
      related parameters in order to calculate process performance figures for process
      optimization of the new magnetic separation device. With separation capacities of
      over 400 g of magnetic particles per liter of separation chamber volume and
      separation efficiencies as well as recovery rates over 99%, the system is able to
      process more than 200 l crude feedstock per day and capture more than 1.6 kg
      target compounds.

PMID- 29058377
TI  - Genome-wide association study of alcohol use disorder identification test (AUDIT)
      scores in 20 328 research participants of European ancestry.
AB  - Genetic factors contribute to the risk for developing alcohol use disorder (AUD).
      In collaboration with the genetics company 23andMe, Inc., we performed a genome
      wide association study of the alcohol use disorder identification test (AUDIT),
      an instrument designed to screen for alcohol misuse over the past year. Our final
      sample consisted of 20 328 research participants of European ancestry (55.3%
      females; mean age = 53.8, SD = 16.1) who reported ever using alcohol. Our results
      showed that the 'chip-heritability' of AUDIT score, when treated as a continuous
      phenotype, was 12%. No loci reached genome-wide significance. The gene ADH1C,
      which has been previously implicated in AUD, was among our most significant
      associations (4.4 * 10-7 ; rs141973904). We also detected a suggestive
      association on chromosome 1 (2.1 * 10-7 ; rs182344113) near the gene KCNJ9, which
      has been implicated in mouse models of high ethanol drinking. Using linkage
      disequilibrium score regression, we identified positive genetic correlations
      between AUDIT score, high alcohol consumption and cigarette smoking. We also
      observed an unexpected positive genetic correlation between AUDIT and educational
      attainment and additional unexpected negative correlations with body mass
      index/obesity and attention-deficit/hyperactivity disorder. We conclude that
      conducting a genetic study using responses to an online questionnaire in a
      population not ascertained for AUD may represent a cost-effective strategy for
      elucidating aspects of the etiology of AUD.

PMID- 29058375
TI  - Patterns of infectious complications in acute myeloid leukemia and
      myelodysplastic syndromes patients treated with 10-day decitabine regimen.
AB  - Decitabine has been explored as a reduced-intensity therapy for older or unfit
      patients with acute myeloid leukemia (AML). To better understand the risk of
      infections during decitabine treatment, we retrospectively examined the culture
      results from each infection-related serious adverse event that occurred among 85
      AML and myelodysplastic syndromes (MDS) patients treated in a prospective
      clinical study using 10-day cycles of decitabine at Washington University School
      of Medicine. Culture results were available for 163 infection-related
      complications that occurred in 70 patients: 90 (55.2%) events were culture
      negative, 32 (19.6%) were gram-positive bacteria, 20 (12.3%) were gram-negative
      bacteria, 12 (7.4%) were mixed, 6 (3.7%) were viral, 2 (1.2%) were fungal, and 1
      (0.6%) was mycobacterial. Infection-related mortality occurred in 3/24 (13%) of
      gram-negative events, and 0/51 gram-positive events. On average, nearly one third
      of patients experienced an infection-related complication with each cycle, and
      the incidence did not decrease during later cycles. In summary, in patients
      receiving 10-day decitabine, infectious complications are common and may occur
      during any cycle of therapy. Although febrile events are commonly culture
      negative, gram-positive infections are the most frequent source of culture
      positive infections, but gram-negative infections represent a significant risk of
      mortality in AML and MDS patients treated with decitabine.

PMID- 29058376
TI  - Prognostic role of tumor necrosis in patients undergoing curative resection for
      gastric gastrointestinal stromal tumor: a multicenter analysis of 740 cases in
      China.
AB  - Tumor necrosis is associated with poor clinical outcomes in many malignancies. We
      aimed to determine whether tumor necrosis was an independent predictor of
      outcomes in gastric gastrointestinal stromal tumors (GISTs). We retrospectively
      analyzed data from 740 patients undergoing curative resection for gastric GIST at
      four centers between 2001 and 2015. Disease-free survival (DFS) was estimated
      with the Kaplan-Meier method, and associations with prognosis were assessed with
      Cox regression models. Tumor necrosis was present in 122 cases (16.5%). The
      prevalence of tumor necrosis increased with higher risk-stratification, including
      0.7%, 7.4%, 17.3%, and 39.3% for very low-, low-, intermediate- and high-risk
      tumors, respectively (P < 0.001). Tumor necrosis was associated with aggressive
      tumor biology, such as larger tumor size, higher mitotic index, tumor rupture,
      and presence of nuclear atypia (all P < 0.05). Multivariate analysis revealed
      that tumor necrosis was an independent predictor of unfavorable DFS (HR: 2.641;
      95% CI: 1.359-5.131; P = 0.004). When stratified by the modified National
      Institutes of Health (NIH) classification, tumor necrosis still independently
      predicted DFS in high-risk patients (P = 0.001) but not in non-high-risk patients
      (P = 0.349). The 5-year DFS rate in high-risk patients with and without tumor
      necrosis was 56.5% and 82.9%, respectively (P = 0.004). Notably, the prognostic
      significance of tumor necrosis was maintained when the patients were stratified
      by age, sex, tumor location, tumor size, and mitotic index (All P < 0.05). Tumor
      necrosis is a useful predictor of outcomes in gastric GIST, especially in high
      risk patients. Based on these results, we recommend that the current NIH
      classification should be further improved and expanded to include tumor necrosis
      as a valuable prognostic indicator.

PMID- 29058378
TI  - Effects of Dairy Products Consumption on Body Weight and Body Composition Among
      Adults: An Updated Meta-Analysis of 37 Randomized Control Trials.
AB  - SCOPE: Effects of dairy consumption on body weight and body composition have been
      inconsistently observed in randomized control trials (RCTs). Our meta-analysis
      aims to systematically evaluate the effects of dairy consumption on body weight
      and body composition among the adults. METHODS AND RESULTS: We conducted a
      comprehensive search of the Cochrane Library, PubMed, and Embase databases of the
      relevant studies from 1966 to Mar 2017 regarding dairy consumption on body weight
      and body composition including body fat, lean mass, and waist circumference (WC).
      The summary results are pooled by using a random-effects meta-analysis. Thirty
      seven RCTs with 184 802 participants are included in this meta-analysis. High
      dairy intervention increased body weight (0.01, 95% CI: -0.25, 0.26, I2 = 78.3%)
      and lean mass (0.37, 95% CI: 0.11, 0.62, I2 = 83.4%); decreased body fat (-0.23,
      95% CI: -0.48, 0.02, I2 = 78.2%) and WC (-1.37, 95% CI: -2.28, -0.46, I2 = 98.9%)
      overall. In the subgroup analysis, we found that consumption of dairy products
      increases body weight (0.36, 95% CI: 0.01, 0.70, I2 = 83.1%) among participants
      without energy restriction. Dairy consumption decreases body weight (-0.64, 95%
      CI: -1.05, -0.24, I2 = 60.2%), body fat (-0.56, 95%CI: -0.95, -0.17, I2 = 66.6%),
      and waist circumference (-2.18, 95%CI: -4.30, -0.06, I2 = 99.0%) among the adults
      with energy restriction. CONCLUSIONS: This meta-analysis suggests a beneficial
      effect of energy-restricted dairy consumption on body weight and body
      composition. However, high dairy consumption in the absence of caloric
      restriction may increase body weight.

PMID- 29058379
TI  - A novel framework for automated, intelligent extraction and analysis of online
      support group discussions for cancer related outcomes.

PMID- 29058380
TI  - Urological outcomes in Australia and New Zealand: who's watching?

PMID- 29058381
TI  - Global assays of fibrinolysis.

PMID- 29058382
TI  - Risk factors of Leptospira infection in Mediterranean periurban micromammals.
AB  - Urbanization of natural areas can change abiotic factors, providing artificial
      sources of humidity in summer and decreasing variation of temperatures in winter.
      Our study aimed at document risk factors of infection in mammal reservoirs of
      pathogenic Leptospira in the human/wildlife interface of a large metropolitan
      area. We hypothesize that survival of Leptospira and thus their prevalence in
      animal reservoirs should be higher in residential areas than in natural habitats,
      especially after the hot, dry Mediterranean summers. We established the
      prevalence of Leptospira spp. and identified the serovars in 353 urine samples
      from micromammals (chiefly the wood mouse Apodemus sylvaticus, n = 266) using
      direct immunofluorescence and PCR. Animals were captured in spring and autumn,
      2011-2012, in two natural parks and two adjacent residential areas in periurban
      Barcelona (NE Spain). Overall observed prevalence of infection was 11%, ranking
      between 8% and 13% in the better represented host species. We observed marked
      differences between seasons; the probability of finding a micromammal infected in
      spring was three times greater than in autumn (almost four times for wood mouse).
      Prevalence was not related with type of habitat, micromammal relative abundance
      or sex of the animal. Three Leptospira species were confirmed: Leptospira
      interrogans (47% of cases), Leptospira borgpetersenii (41%) and Leptospira
      kirschneri (12%). The serovars most commonly detected were those typically hosted
      by rodents, and serovars Ballum and Icterohemorrhagiae were the only ones found
      in autumn. People living in periurban Barcelona and those visiting the natural
      areas of the metropolitan area face hazard of infection with rodent-borne
      Leptospira, especially during spring.

PMID- 29058383
TI  - CRISPR/Cas9-mediated PBP1 and PBP3 mutagenesis induced significant reduction in
      electrophysiological response to sex pheromones in male Chilo suppressalis.
AB  - Pheromone-binding proteins (PBPs) are thought to bind and transport sex
      pheromones onto the olfactory receptors on the dendrite membrane of olfactory
      neurons, and thus play a vital role in sex pheromone perception. However, the
      function of PBPs has rarely been demonstrated in vivo. In this study, two PBPs
      (PBP1 and PBP3) of Chilo suppressalis, one of the most notorious pyralid pests,
      were in vivo functionally characterized using insects with the PBP gene knocked
      out by the CRISPR/Cas9 system. First, through direct injection of PBP-single
      guide RNA (sgRNA)/Cas9 messenger RNA into newly laid eggs, a high rate of target
      gene editing (checked with polled eggs) was induced at 24 h after injection,
      21.3% for PBP1-sgRNA injected eggs and 19.5% for PBP3-sgRNA injected eggs.
      Second, by an in-crossing strategy, insects with mutant PBP1 or PBP3 (both with a
      premature stop codon) were screened, and homozygous mutants were obtained in the
      G3 generation. Third, the mutant insects were measured for electroantennogram
      (EAG) response to female sex pheromones. As a result, both PBP mutant males
      displayed significant reduction in EAG response, and this reduction in PBP1
      mutants was higher than that in PBP3 mutants, indicating a more important role of
      PBP1. Finally, the relative importance of two PBPs and the possible off target
      effect induced by sgRNA-injection are discussed. Taken together, our study
      provides a deeper insight into the function of and interaction between different
      PBP genes in sex pheromone perception of C. suppressalis, as well as a valuable
      reference in methodology for gene functional study in other genes and other moth
      species.

PMID- 29058384
TI  - Nitric oxide for the treatment of preterm infants with severe RDS and pulmonary
      hypertension.
AB  - BACKGROUND: Inhaled nitric oxide (iNO) cannot be recommended for the routine
      treatment of respiratory failure in premature neonates, but it has been suggested
      that the effectiveness of iNO therapy should be further studied in more select
      preterm infants, such as those with persistent pulmonary hypertension of the
      newborn (PPHN). OBJECTIVE: To evaluate the frequency of PPHN in very preterm
      infants with severe respiratory distress syndrome (RDS), to assess the
      effectiveness of iNO in these patients, and to individuate possible predictive
      factors for the response to iNO in preterm infants with RDS. STUDY DESIGN: We
      retrospectively studied infants <30 weeks of gestational age or birth weight
      <1250 g, who were affected by severe RDS and treated with iNO during the first
      week of life. Clinical characteristics of infants with or without
      echocardiographic diagnosis of PPHN were compared, as well as those of responder
      or no responder to iNO therapy. Effectiveness of iNO was evaluated by recording
      changes of MAP, FiO2 , SpO2 /FiO2 ratio, and oxygenation index (OI) before, and 3
      +/- 1, 6 +/- 1, 12 +/- 3, 24 +/- 6, 48 +/- 6, and 72 +/- 12 h after beginning
      therapy. RESULTS: We studied 42 (4.6%) infants, of whom 28 (67%) had PPHN and 14
      (33%) did not. iNO therapy was associated with improved oxygenation in both the
      groups but it was quicker in the PPHN than in the no PPHN group. Multivariate
      analysis showed that FiO2 >0.65, diagnosis of PPHN, and birth weight >750 g
      independently predicts effectiveness of iNO in very preterm infants with RDS.
      CONCLUSION: We found that PPHN is a frequent complication of severe RDS in very
      preterm infants and iNO therapy can improve their oxygenation earlier than in
      infants without PPHN. iNO therapy is not recommended for the routinely treatment
      of RDS in premature neonates but in cases of concurrent diagnosis of PPHN it
      should be considered carefully.

PMID- 29058387
TI  - New Estimates of the Impact of Child Disability on Maternal Employment.

PMID- 29058386
TI  - New mutations in the SLC7A7 gene of two chinese sisters with lysinuric protein
      intolerance.
AB  - Lysinuric protein intolerance (LPI) is an inherited aminoaciduria with an
      autosomal recessive mode of inheritance.The first two cases of sisters being
      diagnosed with LPI in China is contained within this report. In our cases, there
      were two heterozygous mutations in the SLC7A7 gene of the two sisters: deletion
      of c.1387: del C and IVS4+1C>T. One patient was treated with inhaled rGM-CSF for
      1.5 years at 5 MUg/kg two times a day. Her condition is improving with no side
      effects.

PMID- 29058388
TI  - The Impact of Economic Conditions on Participation in Disability Programs:
      Evidence from the Coal Boom and Bust.
AB  - We examine the impact of the coal boom of the 1970's and the coal bust of the
      1980's on disability program participation. These shocks provide clear evidence
      that as the value of labor-market participation increases, disability program
      participation falls. For the Disability Insurance program, the elasticity of
      payments with respect to local earnings is between -0.3 and -0.4 and for
      Supplemental Security Income the elasticity is between -0.4 and -0.7. Consistent
      with a model where qualifying for disability programs is costly, the relationship
      between economic conditions and program participation is much stronger for
      permanent than for transitory economic shocks.

PMID- 29058390
TI  - Benefits of Using Lasers in Dental Treatment Validated.

PMID- 29058389
TI  - Insuring Consumption Against Illness.
AB  - One of the most sizable and least predictable shocks to economic opportunities in
      developing countries is major illness. We investigate the extent to which
      families are able to insure consumption against major illness using a unique
      panel data set from Indonesia that combines excellent measures of health status
      with consumption information. We find that there are significant economic costs
      associated with major illness, and that there is very imperfect insurance of
      consumption over illness episodes. These estimates suggest that public disability
      insurance or subsidies for medical care may improve welfare by providing
      consumption insurance.

PMID- 29058391
TI  - Women: The Changing Face of Dentistry.

PMID- 29058392
TI  - California Women in Dentistry: A  Look Back.
AB  - California's female dentists have experienced many professionaland societal
      challenges. Their earliest achievements and successes are examined,including
      their history in the early California schools of dentistry and dentalsocieties,
      their service and professional practice. A diverse selection of femaledentists
      from California with different professional career paths is profiled.

PMID- 29058393
TI  - The Rise in Old-Age Longevity and the Market for Long-Term Care.

PMID- 29058394
TI  - Female Leaders Essential to Organized Dentistry.

PMID- 29058395
TI  - Changes in the Academe: Women in Dental Education.
AB  - More than 150 years ago, Lucy Hobbs became the first woman in thecountry to enter
      dental school. Today, women represent nearly half of the nation'sentering class,
      more than a third of the faculty and a growing number of administrativeleaders,
      including deans. Evidence illustrates a developing pipeline toward greaternumbers
      and strength of women in dental education, creating a far-reaching impact
      onteaching, learning and patient care in academia, practice and the profession.

PMID- 29058396
TI  - Child Abuse and Abortion Availability.

PMID- 29058397
TI  - Economic Status and Health in Childhood: The Origins of the Gradient.
AB  - The well-known positive association between health and income in adulthood has
      antecedents in childhood. Not only is children's health positively related to
      household income, but the relationship between household income and children's
      health becomes more pronounced as children age. Part of the relationship can be
      explained by the arrival and impact of chronic conditions. Children from lower
      income households with chronic conditions have worse health than do those from
      higher-income households. The adverse health effects of lower income accumulate
      over children's lives. Part of the intergenerational transmission of
      socioeconomic status may work through the impact of parents' income on children's
      health.

PMID- 29058398
TI  - Does California Project the Future of Dentistry?
AB  - If trends continue, the majority of U.S. dental students will soon bewomen.
      However, there is little empirical analysis examining gender differences inthe
      labor supply of dentists and the potential effects on the dental care sector.
      Wehelp fill this data void by examining differences in dentists' hours worked by
      gender,how this has changed over time and the potential implications for the
      current andfuture aggregate labor supply of dentists in California.

PMID- 29058399
TI  - The Evolution of Human Life Expectancy and Intelligence in Hunter-Gatherer
      Economies.
AB  - The economics of hunting and gathering must have driven the biological evolution
      of human characteristics, since hunter-gatherer societies prevailed for the two
      million years of human history. These societies feature huge intergenerational
      resource flows, suggesting that these resource flows should replace fertility as
      the key demographic consideration. It is then theoretically expected that life
      expectancy and brain size would increase simultaneously, as apparently occurred
      during our evolutionary history. The brain here is considered as a direct form of
      bodily investment, but also crucially as facilitating further indirect investment
      by means of learning-by-doing.

PMID- 29058400
TI  - Women in the Boardroom: Reflecting the Changing Gender Demographics of Dentists.
AB  - Even though there are more women in the workplace today thanever before and more
      women than men are now graduating from college, there arerelatively few women who
      hold leadership positions, be it in government, academicsor on corporate boards.

PMID- 29058401
TI  - Access to Food and the Biological Standard of Living: Perspectives on the
      Nutritional Status of Native Americans.

PMID- 29058402
TI  - Employing Calcination as a Facile Strategy to Reduce the Cytotoxicity in CoFe2O4
      and NiFe2O4 Nanoparticles.
AB  - CoFe2O4 and NiFe2O4 nanoparticles (NPs) represent promising candidates for
      biomedical applications. However, in these systems, the knowledge over how
      various physical and chemical parameters influence their cytotoxicity remains
      limited. In this article, we investigated the effect of different calcination
      temperatures over cytotoxicity of CoFe2O4 and NiFe2O4 NPs, which were synthesized
      by a sol-gel proteic approach, toward L929 mouse fibroblastic cells. More
      specifically, we evaluated and compared CoFe2O4 and NiFe2O4 NPs presenting low
      crystallinity (that were calcined at 400 and 250  degrees C, respectively) with
      their highly crystalline counterparts (that were calcined at 800  degrees C). We
      found that the increase in the calcination temperature led to the reduction in
      the concentration of surface defect sites and/or more Co or Ni atoms located at
      preferential crystalline sites in both cases. A reduction in the cytotoxicity
      toward mouse fibroblast L929 cells was observed after calcination at 800  degrees
      C. Combining with inductively coupled plasma mass spectrometry data, our results
      indicate that the calcination temperature can be employed as a facile strategy to
      reduce the cytotoxicity of CoFe2O4 and NiFe2O4, in which higher temperatures
      contributed to the decrease in the dissolution of Co2+ or Ni2+ from the NPs. We
      believe these results may shed new insights into the various parameters that
      influence cytotoxicity in ferrite NPs, which may pave the way for their
      widespread applications in biomedicine.

PMID- 29058403
TI  - Traced on the Timeline: Discovery of Acetylcholine and the Components of the
      Human Cholinergic System in a Primitive Unicellular Eukaryote Acanthamoeba spp.
AB  - Acetylcholine (ACh) is the neurotransmitter of cholinergic signal transduction
      that affects the target cells via muscarinic (mAChR) and nicotinic (nAChR)
      cholinergic receptors embedded in the cell membrane. Of the cholinergic receptors
      that bind to ACh, the mAChRs execute several cognitive and metabolic functions in
      the human central nervous system (CNS). Very little is known about the origins
      and autocrine/paracrine roles of the ACh in primitive life forms. With the recent
      report of the evidence of an ACh binding mAChR1 like receptor in Acanthamoeba
      spp., it was tempting to investigate the origin and functional roles of
      cholinergic G-Protein coupled receptors (GPCRs) in the biology of eukaryotes. We
      inferred the presence of ACh, its synthetic, degradation system, and a signal
      transduction pathway in an approximately ~2.0 billion year old primitive
      eukaryotic cell Acanthamoeba castellanii. Bioinformatics analysis, ligand binding
      prediction, and docking methods were used to establish the origins of enzymes
      involved in the synthesis and degradation of ACh. Notably, we provide evidence of
      the presence of ACh in A. castellanii by colorimetric analysis, which to date is
      the only report of its presence in this primitive unicellular eukaryote. We show
      the evidence for the presence of homology of evolutionary conserved key enzymes
      of the cholinergic system like choline acetyltransferase (ChAT) and
      acetylcholinesterase (AChE) in A. castellanii spp., which were found to be near
      identical to their human counterparts. Tracing the origin, functions of ACh, and
      primeval mAChRs in primitive eukaryotic cells has the potential of uncovering
      covert cholinergic pathways that can be extended to humans in order to understand
      the states of cholinergic deficiency in neurodegenerative diseases (ND).

PMID- 29058404
TI  - Exploring Alkyl Chains in Benzobisthiazole-Naphthobisthiadiazole Polymers: Impact
      on Solar-Cell Performance, Crystalline Structures, and Optoelectronics.
AB  - The shapes and lengths of the alkyl chains of conjugated polymers greatly affect
      the efficiencies of organic photovoltaic devices. This often results in a trade
      off between solubility and self-organizing behavior; however, each material has
      specific optimal chains. Here we report on the effect of alkyl side chains on the
      film morphologies, crystallinities, and optoelectronic properties of new
      benzobisthiazole-naphthobisthiadiazole (PBBT-NTz) polymers. The power conversion
      efficiencies (PCEs) of linear-branched and all-branched polymers range from 2.5%
      to 6.6%; the variations in these PCEs are investigated by atomic force
      microscopy, two-dimensional X-ray diffraction (2D-GIXRD), and transient
      photoconductivity techniques. The best-performing linear-branched polymer,
      bearing dodecyl and decyltetradecyl chains (C12-DT), exhibits nanometer-scale
      fibers along with the highest crystallinity, comprising predominant edge-on and
      partial face-on orientations. This morphology leads to the highest
      photoconductivity and the longest carrier lifetime. These results highlight the
      importance of long alkyl chains for inducing intermolecular stacking, which is in
      contrast to observations made for analogous previously reported polymers.

PMID- 29058405
TI  - Fast on-Site Visual Detection of Active Ricin Using a Combination of Highly
      Efficient Dual-Recognition Affinity Magnetic Enrichment and a Specific Gold
      Nanoparticle Probe.
AB  - Ricin, a highly toxic protein, is a controlled substance by both the Chemical
      Weapons Convention (CWC) and the Biological Weapons Convention (BWC). Therefore,
      fast precaution of potential ricin toxin plays an important role in national
      security and public safety. Herein, a simple, sensitive, and accurate visual
      detection of active ricin in complex samples is presented by combining magnetic
      affinity enrichment with a specific gold nanoparticle (AuNP) probe. In the first
      step, a dual-recognition magnetic absorbent was fabricated by simultaneously
      incorporating two different affinity ligands (concanavalin A and galactosamine)
      on low-foul polymer brushes grafted magnetic beads, which showed remarkable
      multivalent synergy binding capacity for ricin even under complex interfering
      environments. Subsequently, a homoadenine-constituted oligodeoxynucleotide named
      poly(21dA) was conjugated to AuNPs (the poly(21dA)-AuNPs), which served as a
      specific depurination substrate of active ricin. Coralyne can trigger the intact
      poly(21dA)-AuNPs aggregate by forming a non-Watson-Crick homoadenine/coralyne
      complex, but the poly(21dA)-AuNPs after reacting with active ricin failed to form
      this complex due to the loss of adenines. Based on these facts, active ricin can
      be detected as low as 12.5 ng mL-1 with the naked eyes. This detection strategy
      could be well-applied in various ricin-spiked complex matrices. The features such
      as ready operation, facile readout, and easy accessibility make the assay a
      better choice for fast on-site active ricin detection.

PMID- 29058406
TI  - Characterization of Raman Scattering in Solid Samples with Different Particle
      Sizes and Elucidation on the Trends of Particle Size-Dependent Intensity
      Variations in Relation to Changes in the Sizes of Laser Illumination and
      Detection Area.
AB  - We have systematically characterized Raman scatterings in solid samples with
      different particle sizes and investigated subsequent trends of particle size
      induced intensity variations. For this purpose, both lactose powders and pellets
      composed of five different particle sizes were prepared. Uniquely in this study,
      three spectral acquisition schemes with different sizes of laser illuminations
      and detection windows were employed for the evaluation, since it was expected
      that the experimental configuration would be another factor potentially
      influencing the intensity of the lactose peak, along with the particle size
      itself. In both samples, the distribution of Raman photons became broader with
      the increase in particle size, as the mean free path of laser photons, the
      average photon travel distance between consecutive scattering locations, became
      longer under this situation. When the particle size was the same, the Raman
      photon distribution was narrower in the pellets since the individual particles
      were more densely packed in a given volume (the shorter mean free path). When the
      size of the detection window was small, the number of photons reaching the
      detector decreased as the photon distribution was larger. Meanwhile, a large
      window detector was able to collect the widely distributed Raman photons more
      effectively; therefore, the trends of intensity change with the variation in
      particle size were dissimilar depending on the employed spectral acquisition
      schemes. Overall, the Monte Carlo simulation was effective at probing the photon
      distribution inside the samples and helped to support the experimental
      observations.

PMID- 29058407
TI  - Antifungal Phenothiazines: Optimization, Characterization of Mechanism, and
      Modulation of Neuroreceptor Activity.
AB  - New classes of antifungal drugs are an urgent unmet clinical need. One approach
      to the challenge of developing new antifungal drugs is to optimize the antifungal
      properties of currently used drugs with favorable pharmacologic properties, so
      called drug or scaffold repurposing. New therapies for cryptococcal meningitis
      are particularly important given its worldwide burden of disease and limited
      therapeutic options. We report the first systematic structure-activity study of
      the anticryptococcal properties of the phenothiazines. We also show that the
      antifungal activity of the phenothiazine scaffold correlates well with its
      calmodulin antagonism properties and, thereby, provides the first insights into
      the mechanism of its antifungal properties. Guided by this mechanism, we have
      generated improved trifluoperazine derivatives with increased anticryptococcal
      activity and, importantly, reduced affinity for receptors that modulate undesired
      neurological effects. Taken together, these data suggest that phenothiazines
      represent a potentially useful scaffold for further optimization in the search
      for new antifungal drugs.

PMID- 29058408
TI  - Tuning Mobility Separation Factors of Chemical Warfare Agent Degradation Products
      via Selective Ion-Neutral Clustering.
AB  - Combining experimental data with computational modeling, we illustrate the
      capacity of selective gas-phase interactions using neutral gas vapors to yield an
      additional dimension of gas-phase ion mobility separation. Not only are the
      mobility shifts as a function of neutral gas vapor concentration reproducible,
      but also the selective alteration of mobility separation factors is closely
      linked to existing chemical functional groups. Such information may prove
      advantageous in elucidating chemical class and resolving interferences. Using a
      set of chemical warfare agent simulants with nominally the same reduced mobility
      values as a test case, we illustrate the ability of the drift-gas doping approach
      to achieve separation of these analytes. In nitrogen, protonated forms of
      dimethyl methyl phosphonate (DMMP) and methyl phosphonic acid (MPA) exhibit the
      reduced mobility values of 1.99 +/- 0.01 cm2 V-1s-1 at 175  degrees C. However,
      when the counter current drift gas of the system is doped with 2-propanol at 20
      MUL/h, full baseline resolution of the two species is possible. By varying the
      concentration of the neutral modifier, the separation factor of the respective
      clusters can be adjusted. For the two species examined and at a 2-propanol flow
      rate of 160 MUL/h, MPA demonstrated the greatest shift in mobility (1.58 cm2V-1s
      1) compared the DMMP monomer (1.63 cm2V-1s-1). Meanwhile, the DMMP dimer
      experienced no change in mobility (1.45 cm2V-1s-1). The enhancement of separation
      factors appears to be brought about by the differential clustering of neutral
      modifiers onto different ions and can be explained by a model which considers the
      transient binding of a single 2-propanol molecule during mobility measurements.
      Furthermore, the application of the binding models not only provides a
      thermodynamic foundation for the results obtained but also creates a predictive
      tool toward a quantitative approach.

PMID- 29058409
TI  - New Emission Factors and Efficiencies from in-Field Measurements of Traditional
      and Improved Cookstoves and Their Potential Implications.
AB  - Household cooking using solid biomass fuels is a major global health and
      environmental concern. As part of the Research on Emissions Air quality Climate
      and Cooking Technologies in Northern Ghana study, we conducted 75 in-field
      uncontrolled cooking tests designed to assess emissions and efficiency of the
      Gyapa woodstove, Philips HD4012, threestone fire and coalpot (local charcoal
      stove). Emission factors (EFs) were calculated for carbon monoxide (CO), carbon
      dioxide (CO2), and particulate matter (PM). Moreover, modified combustion (MCE),
      heat transfer (HTE) and overall thermal efficiencies (OTE) were calculated across
      a variety of fuel, stove and meal type combinations. Mixed effect models suggest
      that compared to traditional stove/fuel combinations, the Philips burning wood or
      charcoal showed significant fuel and energy based EF differences for CO, but no
      significant PM changes with wood fuel. MCEs were significantly higher for Philips
      wood and charcoal-burning stoves compared to the threestone fire and coalpot. The
      Gyapa emitted significantly higher ratios of elemental to organic carbon. Fuel
      moisture, firepower and MCE fluctuation effects on stove performance were
      investigated with mixed findings. Results show agreement with other in-field
      findings and discrepancies with some lab-based findings, with important
      implications for estimated health and air quality impacts.

PMID- 29058411
TI  - Molecularly Imprinted Photo-electrochemical Sensor for Human Epididymis Protein 4
      Based on Polymerized Ionic Liquid Hydrogel and Gold Nanoparticle/ZnCdHgSe Quantum
      Dots Composite Film.
AB  - A novel ionic liquid, 3-{[{4-[((carbamoyl)amino)ethyl methacrylate]butyl}
      ((carbamoyl)amino)ethyl methacrylate]propyl}-1-ethenyl-1H-imidazol-3-ium bromide
      (CCPEimBr) functionalized with vinyl, amino, and methacrylate groups, was
      synthesized and characterized with 1H NMR, FTIR, and HPLC-MS techniques. CCPEimBr
      was adopted as the functional monomer to prepare a molecularly imprinted
      polymerized ionic liquid hydrogel film on a glassy carbon electrode surface for
      human epididymis protein 4 (HE4) sensing. Gold nanoparticles (AuNPs) and ZnCdHgSe
      QDs were incorporated into the imprinted film as photo-electric active materials.
      The photocurrent response was measured to investigate the sensing performance of
      the imprinted sensors toward HE4. The imprinted photo-electrochemical sensor
      shows excellent selectivity, sensitivity, stability, and accuracy for HE4
      determination. Experimental conditions including incubation time and pH value for
      determining HE4 were optimized in this study. The photocurrent variation (DeltaI)
      decreased with increasing HE4 concentration (cHE4), and it was linearly
      proportional to cHE4 varied from 25 pg mL-1 to 4.0 ng mL-1. The detection limit
      of the imprinted sensor for determining HE4 was estimated to be 15.4 pg mL-1 (S/N
      = 3). The imprinted photo-electrochemical sensor was used to determine HE4 in
      human serum samples accurately.

PMID- 29058410
TI  - Spin System Modeling of Nuclear Magnetic Resonance Spectra for Applications in
      Metabolomics and Small Molecule Screening.
AB  - The exceptionally rich information content of nuclear magnetic resonance (NMR)
      spectra is routinely used to identify and characterize molecules and molecular
      interactions in a wide range of applications, including clinical biomarker
      discovery, drug discovery, environmental chemistry, and metabolomics. The set of
      peak positions and intensities from a reference NMR spectrum generally serves as
      the identifying signature for a compound. Reference spectra normally are
      collected under specific conditions of pH, temperature, and magnetic field
      strength, because changes in conditions can distort the identifying signatures of
      compounds. A spin system matrix that parametrizes chemical shifts and coupling
      constants among spins provides a much richer feature set for a compound than a
      spectral signature based on peak positions and intensities. Spin system matrices
      expand the applicability of NMR spectral libraries beyond the specific conditions
      under which data were collected. In addition to being able to simulate spectra at
      any field strength, spin parameters can be adjusted to systematically explore
      alterations in chemical shift patterns due to variations in other experimental
      conditions, such as compound concentration, pH, or temperature. We present
      methodology and software for efficient interactive optimization of spin
      parameters against experimental 1D-1H NMR spectra of small molecules. We have
      used the software to generate spin system matrices for a set of key mammalian
      metabolites and are also using the software to parametrize spectra of small
      molecules used in NMR-based ligand screening. The software, along with optimized
      spin system matrix data for a growing number of compounds, is available from
      http://gissmo.nmrfam.wisc.edu/ .

PMID- 29058412
TI  - Electronic Conductivity in a Porous Vanadyl Prussian Blue Analogue upon Air
      Exposure.
AB  - Exposure to humid O2 or ambient air affords a 5-order-of-magnitude increase in
      electronic conductivity of a new Prussian blue analogue incorporating CoII and
      VIV-oxo units. Oxidation produces a mixed-valence framework, where the O2
      exposure time controls the VIV/VV ratio and thereby the material's conductivity.
      The oxidized framework shows an intervalence charge-transfer band at ca. 4200 cm
      1, consistent with mixed valence. The mixed-valence frameworks show
      semiconducting behavior with conductivity values of 10-5 S.cm-1 at room
      temperature and 10-4 S.cm-1 at 100  degrees C and activation energies of ca. 0.3
      eV. N2 adsorption measurements at 77 K show that these materials possess
      permanent porosity before and after oxidation with Brunauer-Emmett-Teller surface
      areas of 340 and 370 m2.g-1, respectively.

PMID- 29058414
TI  - Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry Characterization
      of Gangliosides in Biological Samples.
AB  - The hydrophilic interaction liquid chromatography (HILIC) coupled to a negative
      ion electrospray ionization tandem mass spectrometry (ESI-MS/MS) method has been
      developed for the identification of a wide range of gangliosides in biological
      samples. Gangliosides consist of a backbone of sphingoid base and a polar
      oligosaccharide chain containing at least one sialic acid. Gangliosides are
      extracted by chloroform-methanol-water mixture, where an upper aqueous layer
      containing gangliosides and other polar lipid subclasses is further purified by
      C18 solid-phase extraction. The optimization of chromatographic conditions
      includes the column selection, mobile-phase composition, pH value, buffer type,
      and concentration with the goal to achieve the best chromatographic resolution
      and MS sensitivity. The identification of gangliosides and other polar lipids is
      based on accurate m/z values of [M-H]- ions and fragment ions as well measured by
      high-resolution MS. The detailed interpretation of MS/MS spectra enables the
      generalization of fragmentation pathways, which is then used for the
      differentiation of a, b, and c series of gangliosides. The structural assignment
      is further confirmed by agreement with the predicted retention behavior in HILIC
      mode on the basis of the correlation among the ganglioside retention, the number
      of saccharide units, and their sequence. The final HILIC/ESI-MS/MS method is
      applied for the analysis of porcine brain, human kidney, lungs, plasma, and
      erythrocytes resulting in unambiguous identification of 145 ganglioside species
      from 19 subclasses, which represents the highest number of reported gangliosides.
      Moreover, 71 sulfatides and 59 polar phospholipids (phosphatidylserines,
      phosphatidylinositols, lysophosphatidylinositols, and phosphatidylglycerols) are
      detected within a 15 min run.

PMID- 29058413
TI  - Mining High-Complexity Motifs in Glycans: A New Language To Uncover the Fine
      Specificities of Lectins and Glycosidases.
AB  - Knowledge of lectin and glycosidase specificities is fundamental to the study of
      glycobiology. The primary specificities of such molecules can be uncovered using
      well-established tools, but the complex details of their specificities are
      difficult to determine and describe. Here we present a language and algorithm for
      the analysis and description of glycan motifs with high complexity. The language
      uses human-readable notation and wildcards, modifiers, and logical operators to
      define motifs of nearly any complexity. By applying the syntax to the analysis of
      glycan-array data, we found that the lectin AAL had higher binding where fucose
      groups are displayed on separate branches. The lectin SNA showed gradations in
      binding based on the length of the extension displaying sialic acid and on
      characteristics of the opposing branches. A new algorithm to evaluate changes in
      lectin binding upon treatment with exoglycosidases identified the primary
      specificities and potential fine specificities of an alpha1-2-fucosidase and an
      alpha2-3,6,8-neuraminidase. The fucosidase had significantly lower action where
      sialic acid neighbors the fucose, and the neuraminidase showed statistically
      lower action where alpha1-2 fucose neighbors the sialic acid or is on the
      opposing branch. The complex features identified here would have been
      inaccessible to analysis using previous methods. The new language and algorithms
      promise to facilitate the precise determination and description of lectin and
      glycosidase specificities.

PMID- 29058415
TI  - Online Simultaneous Hydrogen/Deuterium Exchange of Multitarget Gas-Phase
      Molecules by Electrospray Ionization Mass Spectrometry Coupled with Gas
      Chromatography.
AB  - In this study, a hydrogen/deuterium (H/D) exchange method using gas
      chromatography-electrospray ionization/mass spectrometry (GC-ESI/MS) was first
      investigated as a novel tool for online H/D exchange of multitarget analytes. The
      GC and ESI source were combined with a homemade heated column transfer line. GC
      ESI/MS-based H/D exchange occurs in an atmospheric pressure ion source as a
      result of reacting the gas-phase analyte eluted from GC with charged droplets of
      deuterium oxide infused as the ESI spray solvent. The consumption of the
      deuterated solvent at a flow rate of 2 MUL min-1 was more economical than that in
      online H/D exchange methods reported to date. In-ESI-source H/D exchange by GC
      ESI/MS was applied to 11 stimulants with secondary amino or hydroxyl groups.
      After H/D exchange, the spectra of the stimulants showed unexchanged, partially
      exchanged, and fully exchanged ions showing various degrees of exchange. The
      relative abundances corrected for naturally occurring isotopes of the fully
      exchanged ions of stimulants, except for etamivan, were in the range 24.3-85.5%.
      Methylephedrine and cyclazodone showed low H/D exchange efficiency under acidic,
      neutral, and basic spray solvent conditions and nonexchange for etamivan with an
      acidic phenolic OH group. The in-ESI-source H/D exchange efficiency by GC-ESI/MS
      was sufficient to determine the number of hydrogen by elucidation of
      fragmentation from the spectrum. Therefore, this online H/D exchange technique
      using GC-ESI/MS has potential as an alternative method for simultaneous H/D
      exchange of multitarget analytes.

PMID- 29058416
TI  - Complete NMR Assignment of Succinimide and Its Detection and Quantification in
      Peptides and Intact Proteins.
AB  - Detecting and quantifying post-translational modifications (PTMs) in full-length
      proteins is a challenge, especially in the case of spontaneously occurring,
      nonenzymatic PTMs. Such a PTM is the formation of succinimide (Snn) in a protein
      that occurs spontaneously in prone primary sequences and leads typically to an
      equilibrium between Snn and its hydrolysis products isoaspartate (isoAsp) and
      aspartate. In order to detect these modifications in proteins by NMR
      spectroscopy, chemical shift assignments of reference compounds are required. We
      used peptide synthesis and 2D NMR spectroscopy to assign all 1H and 13C chemical
      shifts of Snn and isoAsp and found characteristic chemical shift correlations. To
      provide chemical shift reference data suitable for comparison with data of
      denatured proteins, we repeated the assignment in 7 M urea (pH 2.3) and in DMSO.
      Most characteristic of Snn are the two downfield shifted carbonyl chemical
      shifts, the chemical shift correlations of Cbeta-Hbeta of Snn and Calpha-Halpha
      of the succeeding residue which are clearly distinct from random coil chemical
      shift correlations. The characteristic 2D NMR fingerprints of Snn were used to
      detect and quantify this PTM in the model protein lysozyme, the biotherapeutic
      filgrastim, and the Fc part of immunoglobulin G1. Mass spectrometry (MS) was
      applied as an additional independent method. The orthogonality of the NMR and MS
      techniques allows cross-validation, which is especially important to search for
      subtle PTMs in proteins. Studying PTMs by NMR spectroscopy is a promising method
      to analyze proteins and peptides from natural sources, recombinant expression, or
      chemical synthesis.

PMID- 29058417
TI  - Cell-Permeable, MMP-2 Activatable, Nickel Ferrite and His-Tagged Fusion Protein
      Self-Assembled Fluorescent Nanoprobe for Tumor Magnetic-Targeting and Imaging.
AB  - Matrix metalloproteinases (MMPs) activatable imaging probe has been explored for
      tumor detection. However, activation of the probe is mainly done in the
      extracellular space without intracellular uptake of the probe for more
      sensitivity. Although cell-penetrating peptides (CPPs) have been demonstrated to
      enable intracellular delivery of the imaging probe, they nevertheless encounter
      off-target delivery of the cargos to normal tissues. Herein, we have developed a
      dual MMP-2-activatable and tumor cell-permeable magnetic nanoprobe to
      simultaneously achieve selective and intracellular tumor imaging. This novel
      imaging probe was constructed by self-assembling a hexahistidine-tagged (His
      tagged) fluorescent fusion protein chimera and nickel ferrite nanoparticles via a
      chelation mechanism. The His-tagged fluorescent protein chimera consisted of a
      red fluorescent protein mCherry that acted as the fluorophore, the low-molecular
      weight protamine peptide as the CPP, and the MMP-2 cleavage sequence fused with
      the hexahistidine tag, whereas the nickel ferrite nanoparticles functioned as the
      His-tagged protein binder and also the fluorescent quencher. Both in vitro and in
      vivo results revealed that this imaging probe would not only remain nonpermeable
      to normal tissues, thereby offsetting the nonselective cellular uptake, but was
      also suppressed of fluorescent signals during magnetic tumor-targeting in the
      circulation, primarily because of the masking of the CPP activity and quenching
      of the fluorophore by the associated NiFe2O4 nanoparticles. However, these
      properties were recovered or "turned on" by the action of tumor-associated MMP-2
      stimuli, leading to cell penetration of the nanoprobes as well as fluorescence
      restoration and visualization within the tumor cells. In this regard, the
      presented tumor-activatable and cell-permeable system deems to be an appealing
      platform to achieve selective tumor imaging and intracellular protein delivery.
      Its impact is therefore significant, far-reaching, and wide-spread.

PMID- 29058418
TI  - Allosteric Control of Oxidative Catalysis by a DNA Rotaxane Nanostructure.
AB  - DNA is a versatile construction material for the bottom-up assembly of structures
      and functional devices in the nanoscale. Additionally, there are specific
      sequences called DNAzymes that can fold into tertiary structures that display
      catalytic activity. Here we report the design of an interlocked DNA nanostructure
      that is able to fine-tune the oxidative catalytic activity of a split DNAzyme in
      a highly controllable manner. As scaffold, we employed a double-stranded DNA
      rotaxane for its ability to undergo programmable and predictable conformational
      changes. Precise regulation of the DNAzyme's oxidative catalysis can be achieved
      by external stimuli (i.e., addition of release oligos) that modify the spatial
      arrangement within the system, without interfering with the catalytic core,
      similar to structural rearrangements that occur in allosterically controlled
      enzymes. We show that multiple switching steps between the active and inactive
      conformations can be performed consistent with efficient regulation and robust
      control of the DNA nanostructure.

PMID- 29058419
TI  - Strain-Promoted Nitration of 3-Cyclopropylideneprop-2-en-1-ones and the
      Application for the Synthesis of Pyrroles.
AB  - The tunable nucleophilic nitration of 3-cyclopropylideneprop-2-en-1-ones with
      cheap sodium nitrite is described. This transformation proceeds with the
      assistance of a strained cyclopropane ring and allows for a divergent route to
      various synthetically useful beta,gamma-dinitro or gamma-mononitro adducts in
      high yields with exclusive regio- and stereoselectivity. Additionally, a wide
      array of valuable functionalized N-unprotected pyrroles is achieved from the
      resulting beta,gamma-dinitro compounds via reductive cyclization strategy.

PMID- 29058420
TI  - Exploration of Biological Markers of Feed Efficiency in Young Bulls.
AB  - The efficiency with which ruminants convert feed to desirable products is
      difficult to measure under normal commercial settings. We explored the use of
      potential biological markers from easily obtainable samples, that is, blood,
      hair, and feces, to characterize potential causes of divergent efficiency when
      considered as residual feed intake (RFI) or feed conversion efficiency (FCE). A
      total of 54 Charolais bulls, 20 in period 1 and 34 in period 2, were examined for
      individual dry matter intake (DMI) and growth. Bulls were offered a diet of 70:30
      wrapped grass silage to concentrate for 99 d. At the conclusion of the test
      period, blood samples were collected for the determination of vitamins B2 and B6,
      and plasma used for the determination of metabolites, natural isotopic 15N
      abundance (15N NIA, expressed as delta15N 0/00) and fractionation (Delta15Nplasma
      proteins-diet and Delta13Cplasma proteins-diet) and near-infrared spectroscopy
      (NIRS). Feces were analyzed by NIRS. Bulls were slaughtered at 15-17 months of
      age and carcass characteristics determined. Bulls were ranked according to RFI
      with extremes (SD +/- 0.5; n = 31) classified as either efficient (Neg-RFI) or
      inefficient (Pos-RFI). Extreme bulls were then classified for FCE (high vs low
      FCE), changing the groups. Pos-RFI bulls consumed 14% more feed than Neg-RFI
      bulls for the same level of weight gain. Low FCE bulls tended to eat more, but
      had lower weight gains than high FCE bulls. No differences were detected in
      carcass conformation, fat scores, hot carcass weight, or dressing percentage.
      Yet, heart and bladder weights were heavier in Pos-RFI, and rumen weight tended
      to be heavier in Pos-RFI bulls. RFI did not affect bulk 15N or 13C fractionation.
      A negative correlation was observed between FCE and Delta15Nplasma proteins-diet.
      Inefficient bulls (Pos-RFI) had higher delta15N in glycine compared to Neg-RFI
      bulls. Similarly, metabolomic analysis showed a tendency for concentrations of
      glycine and sarcosine to be elevated in Pos-RFI bulls, whereas aspartic acid and
      carnosine tended to be elevated, and serine tended to be lower in High FCE. Among
      vitamins, only flavin adenine dinucleotide concentration was higher in the blood
      of bulls with High FCE. These results suggest that the two feed efficiency
      metrics differ in the underlying mechanisms of metabolism, where RFI is driven by
      differences in the energetic requirements of visceral organs and the extent of AA
      catabolism.

PMID- 29058421
TI  - Authentication of Zanthoxylum Species Based on Integrated Analysis of Complete
      Chloroplast Genome Sequences and Metabolite Profiles.
AB  - We performed chloroplast genome sequencing and comparative analysis of two
      Rutaceae species, Zanthoxylum schinifolium (Korean pepper tree) and Z. piperitum
      (Japanese pepper tree), which are medicinal and culinary crops in Asia. We
      identified more than 837 single nucleotide polymorphisms and 103
      insertions/deletions (InDels) based on a comparison of the two chloroplast
      genomes and developed seven DNA markers derived from five tandem repeats and two
      InDel variations that discriminated between Korean Zanthoxylum species.
      Metabolite profile analysis pointed to three metabolic groups, one with Korean Z.
      piperitum samples, one with Korean Z. schinifolium samples, and the last
      containing all the tested Chinese Zanthoxylum species samples, which are
      considered to be Z. bungeanum based on our results. Two markers were capable of
      distinguishing among these three groups. The chloroplast genome sequences
      identified in this study represent a valuable genomics resource for exploring
      diversity in Rutaceae, and the molecular markers will be useful for
      authenticating dried Zanthoxylum berries in the marketplace.

PMID- 29058422
TI  - Foldamer-Mediated Structural Rearrangement Attenuates Abeta Oligomerization and
      Cytotoxicity.
AB  - The conversion of the native random coil amyloid beta (Abeta) into amyloid fibers
      is thought to be a key event in the progression of Alzheimer's disease (AD). A
      significant body of evidence suggests that the highly dynamic Abeta oligomers are
      the main causal agent associated with the onset of AD. Among many potential
      therapeutic approaches, one is the modulation of Abeta conformation into off
      pathway structures to avoid the formation of the putative neurotoxic Abeta
      oligomers. A library of oligoquinolines was screened to identify antagonists of
      Abeta oligomerization, amyloid formation, and cytotoxicity. A dianionic
      tetraquinoline, denoted as 5, was one of the most potent antagonists of Abeta
      fibrillation. Biophysical assays including amyloid kinetics, dot blot, ELISA, and
      TEM show that 5 effectively inhibits both Abeta oligomerization and fibrillation.
      The antagonist activity of 5 toward Abeta aggregation diminishes with sequence
      and positional changes in the surface functionalities. 5 binds to the central
      discordant alpha-helical region and induces a unique alpha-helical conformation
      in Abeta. Interestingly, 5 adjusts its conformation to optimize the antagonist
      activity against Abeta. 5 effectively rescues neuroblastoma cells from Abeta
      mediated cytotoxicity and antagonizes fibrillation and cytotoxicity pathways of
      secondary nucleation induced by seeding. 5 is also equally effective in
      inhibiting preformed oligomer-mediated processes. Collectively, 5 induces strong
      secondary structure in Abeta and inhibits its functions including
      oligomerization, fibrillation, and cytotoxicity.

PMID- 29058423
TI  - Spectrally Selective Spectroscopy of Native Ca-Containing and Ba-Substituted LH1
      RC Core Complexes from Thermochromatium tepidum.
AB  - The LH1-RC core complex from the thermophilic photosynthetic purple sulfur
      bacterium Thermochromatium tepidum has recently attracted interest of many
      researchers because of its several unique properties, such as increased
      robustness against environmental hardships and the much red-shifted near-infrared
      absorption spectrum of the LH1 antenna exciton polarons. The known near-atomic
      resolution crystal structure of the complex well supported this attention. Yet
      several mechanistic aspects of the complex prominence remained to be understood.
      In this work, samples of the native, Ca2+-containing core complexes were
      investigated along with those destabilized by Ba2+ substitution, using various
      spectrally selective steady-state and picosecond time-resolved spectroscopic
      techniques at physiological and cryogenic temperatures. As a result, the current
      interpretation of exciton spectra of the complex was significantly clarified.
      Specifically, by evaluating the homogeneous and inhomogeneous compositions of the
      spectra, we showed that there is little to no effect of cation substitution on
      the dynamic or kinetic properties of antenna excitons. Reasons of the extra red
      shift of absorption/fluorescence spectra observed in the Ca-LH1-RC and not in the
      Ba-LH1-RC complex should thus be searched in subtle structural differences
      following the inclusion of different cations into the core complex scaffold.

PMID- 29058424
TI  - Site-Selective, Copper-Mediated O-Arylation of Carbohydrate Derivatives.
AB  - Site-selective functionalization of hydroxy groups in sugar derivatives is a
      major challenge in carbohydrate synthesis. Methods for achieving this goal will
      provide efficient access to new sugar-derived chemical building blocks and will
      facilitate the preparation or late-stage modification of complex oligosaccharides
      for applications in glycobiology research and drug discovery. Here, we describe
      site-selective, copper-promoted couplings of boronic acids with carbohydrate
      derivatives. These reactions generate sugar-derived aryl ethers, a structural
      class that is challenging to generate by other means and has not previously been
      accessed in a site-selective fashion. Experimental evidence and computational
      modeling suggest that the formation of a sugar-derived boronic ester intermediate
      is crucial to the selectivity of these processes, accelerating the arylation of
      an adjacent hydroxy group. The results demonstrate how the interactions of sugars
      with boron compounds can be combined with transition metal catalysis to achieve
      new chemical reactivity.

PMID- 29058425
TI  - Sophoridine from Sophora Flower Attenuates Ovariectomy Induced Osteoporosis
      through the RANKL-ERK-NFAT Pathway.
AB  - An imbalance in osteogenesis and osteoclastogenesis is a crucial pathological
      factor in the development of osteoporosis. Osteoclasts (OCs) play a pivotal role
      in osteoporosis, whose new therapy exploration has been focused on the
      suppression of OC formation. Sophoridine is found from the Chinese traditional
      food sophora flower to exhibit anti-osteoporosis capacity by screening. This
      study is focused on its anti-osteoporosis mechanism evaluation. The anti
      osteoporosis effect of sophoridine, (15 mg kg-1 body), was evaluated in
      ovariectomized (OVX) mice by monitoring changes in bone histomorphometry index,
      formation of osteoclasts from blood-derived mononuclear cells, and changes in the
      synthesis of pro-osteoclastogenic cytokines. Signal pathways were investigated by
      QPCR, Western blot, and immunofluorescence. Sophoridine has a significant anti
      osteoporosis effect in vivo, which can inhibit RANKL-induced OC formation, the
      appearance of OC-specific marker genes, and OC marker protein in vitro.
      Mechanistically, sophoridine dose- and time-dependently blocks the RANKL-induced
      OC formation and the activation of ERK and c-Fos as well as the induction and
      nucleus translocation of NFATc1. Sophora flower might be a useful alternative
      functional food in preventing or treating osteoporosis.

PMID- 29058426
TI  - Reversible Redox Switching of Chromophoric Phenylmethylenepyrans by Carbon-Carbon
      Bond Making/Breaking.
AB  - Electrochromic organic systems that can undergo substantial variation of their
      optical properties upon electron stimulus are of high interest for the
      development of functional materials. In particular, devices based on radical
      dimerization are appropriate because of the effectiveness and speed of carbon
      carbon bond making/breaking. Phenylmethylenepyrans are organic chromophores which
      are well suited for such purposes since their oxidation leads to the reversible
      formation of bispyrylium species by radical dimerization. In this paper, we show
      that the redox and spectroscopic properties of phenylmethylenepyrans can be
      modulated by adequate variation of the substituting group on the para position of
      the phenyl moiety, as supported by DFT calculations. This redox switching is
      reversible over several cycles and is accompanied by a significant modification
      of the UV-vis spectrum of the chromophore, as shown by time-resolved
      spectroelectrochemistry in thin-layer conditions.

PMID- 29058427
TI  - Tracking Changes of Hexabromocyclododecanes during the Refining Process in
      Peanut, Corn, and Soybean Oils.
AB  - Hexabromocyclododecanes (HBCDs) are harmful compounds, which could be taken up by
      plants and occur in vegetable oils. In this study, we systematically tracked the
      changes of HBCDs during different refining processes in peanut, corn, and soybean
      oils in China. The refining processes were efficient at removing the
      concentrations of total HBCDs (?HBCDs), although the levels did increase for
      peanut and corn oils during the neutralization and bleaching steps. Quite
      significant reductions in the ?HBCD concentrations were observed for soybean oils
      (71-100%) through refining. alpha-HBCD and ?HBCD levels were significantly and
      positively correlated with the peroxidation value (PV), suggesting that PV might
      be an indicator reflecting the changes of alpha-HBCD and ?HBCDs during the oil
      refining processes. HBCD intakes from vegetable oils represented a low concern
      for public health. The results might be helpful for quality and process control
      with a view to minimize the levels of HBCDs in vegetable oils.

PMID- 29058428
TI  - Effect of Germination and Fermentation on Carbohydrate Composition of Australian
      Sweet Lupin and Soybean Seeds and Flours.
AB  - This study investigated the effect of germination and fermentation on the
      composition of carbohydrates in Australian sweet lupin. Specifically, the amount
      of sugars (sucrose, fructose, and glucose), starch, oligosaccharides (verbascose,
      stachyose, and raffinose), and dietary fiber were measured in germinated lupin
      seeds and fermented lupin flour, and compared with those in soy. High performance
      liquid chromatography coupled with refractive index was employed for quantitation
      of sugars, starch, and oligosaccharides, and gas chromatography coupled with a
      flame ionization detector was used for quantitation of simple sugars in total,
      and soluble, and insoluble dietary fiber. The enzyme activities of alpha-amylase
      and alpha-glucosidase were compared before and after germination or fermentation.
      The alpha-amylase activity in germinated lupin increased to  ~17 nmol/mL/min/0.1
      g and in germinated soy~32; in fermented lupin, the activity increased to ~52,
      while in fermented soy it decreased to ~20. In general, germination or
      fermentation decreased the oligosaccharide content, and increased the total sugar
      in samples (p < 0.05). Total oligosaccharides in lupin after uncontrolled
      germination were reduced by 98% to 6 mg/g, and after controlled germination
      reduced by 44% to 86 mg/g. Fermentation with yogurt culture lowered the content
      of total oligosaccharides due to 94% decrease in stachyose. Total
      oligosaccharides in soy flour prior to fermentation were 180 mg/g and
      significantly decreased to ~124 mg/g in fermented soy. Germination did not affect
      the starch content. There was no significant change in the amounts of total,
      soluble, and insoluble dietary fiber after germination or fermentation of lupin
      except for galactose, which was significantly reduced in germinated lupin seeds.
      Soluble dietary fiber in germinated soy significantly increased. Germination and
      fermentation are simple and effective techniques to reduce the oligosaccharides
      while maintaining the composition of dietary fibers.

PMID- 29058429
TI  - Manipulating Ferroelectrics through Changes in Surface and Interface Properties.
AB  - Ferroelectric materials are used in many applications of modern technologies
      including information storage, transducers, sensors, tunable capacitors, and
      other novel device concepts. In many of these applications, the ferroelectric
      properties, such as switching voltages, piezoelectric constants, or stability of
      nanodomains, are crucial. For any application, even for material
      characterization, the material itself needs to be interfaced with electrodes. On
      the basis of the structural, chemical, and electronic properties of the
      interfaces, the measured material properties can be determined by the interface.
      This is also true for surfaces. However, the importance of interfaces and
      surfaces and their effect on experiments are often neglected, which results in
      many dramatically different experimental results for nominally identical samples.
      Therefore, it is crucial to understand the role of the interface and surface
      properties on internal bias fields and the domain switching process. Here, the
      nanoscale ferroelectric switching process and the stability of nanodomains for
      Pb(Zr,Ti)O3 thin films are investigated by using scanning probe microscopy.
      Interface and surface properties are modulated through the selection/redesign of
      electrode materials as well as tuning the surface-near oxygen vacancies, which
      both can result in changes of the electric fields acting across the sample, and
      consequently this controls the measured ferroelectric and domain retention
      properties. By understanding the role of surfaces and interfaces, ferroelectric
      properties can be tuned to eliminate the problem of asymmetric domain stability
      by combining the effects of different electrode materials. This study forms an
      important step toward integrating ferroelectric materials in electronic devices.

PMID- 29058430
TI  - Nucleation and Growth of Covalent Organic Frameworks from Solution: The Example
      of COF-5.
AB  - The preparation of two-dimensional covalent organic frameworks (2D COFs) with
      large crystalline domains and controlled morphology is necessary for realizing
      the full potential of their atomically precise structures and uniform, tailorable
      porosity. Currently 2D COF syntheses are developed empirically, and most
      materials are isolated as insoluble and unprocessable powders with typical
      crystalline domain sizes smaller than 50 nm. Little is known about their
      nucleation and growth processes, which involve a combination of covalent bond
      formation, degenerate bond exchange, and noncovalent stacking processes. A deeper
      understanding of the chemical processes that lead to COF polymerization and
      crystallization is key to achieving improved materials quality and control. Here,
      we report a kinetic Monte Carlo (KMC) model that describes the formation of a
      prototypical boronate-ester linked 2D COF known as COF-5 from its 2,3,6,7,10,11
      hexahydroxytriphenylene and 1,4-phenylene bis(boronic acid) monomers in solution.
      The key rate parameters for the KMC model were derived from experimental
      measurements when possible and complemented with reaction pathway analyses,
      molecular dynamics simulations, and binding free-energy calculations. The
      essential features of experimentally measured COF-5 growth kinetics are
      reproduced well by the KMC simulations. In particular, the simulations
      successfully captured a nucleation process followed by a subsequent growth
      process. The nucleating species are found to be relatively small, multilayer
      structures that form through multiple pathways. During the growth of COF-5,
      extensions in the lateral (in-plane) and vertical (stacking) directions are both
      seen to be linear with respect to time and are dominated by monomer addition and
      oligomer association, respectively. Finally, we show that the experimental
      observations of increased average crystallite size with the addition of water are
      modeled accurately by the simulations. These results will inform the rational
      development of 2D COF polymerizations by controlling the rate of nucleation,
      thereby increasing their materials quality.

PMID- 29058431
TI  - Concise Synthesis of (-)-Hodgkinsine, (-)-Calycosidine, (-)-Hodgkinsine B, (-)
      Quadrigemine C, and (-)-Psycholeine via Convergent and Directed Modular Assembly
      of Cyclotryptamines.
AB  - The enantioselective total synthesis of (-)-hodgkinsine, (-)-calycosidine, (-)
      hodgkinsine B, (-)-quadrigemine C, and (-)-psycholeine through a diazene-directed
      assembly of cyclotryptamine fragments is described. Our synthetic strategy
      enables multiple and directed assembly of intact cyclotryptamine subunits for
      convergent synthesis of highly complex bis- and tris-diazene intermediates.
      Photoextrusion of dinitrogen from these intermediates enables completely
      stereoselective formation of all C3a-C3a' and C3a-C7' carbon-carbon bonds and all
      the associated quaternary stereogenic centers. In a representative example,
      photoextrusion of three dinitrogen molecules from an advanced intermediate in a
      single-step led to completely controlled introduction of four quaternary
      stereogenic centers and guided the assembly of four cyclotryptamine monomers en
      route to (-)-quadrigemine C. The synthesis of these complex diazenes was made
      possible through a new methodology for synthesis of aryl-alkyl diazenes using
      electronically attenuated hydrazine-nucleophiles for a silver-promoted addition
      to C3a-bromocyclotryptamines. The application of Rh- and Ir-catalyzed C-H
      amination reactions in complex settings were used to gain rapid access to C3a-
      and C7-functionalized cyclotryptamine monomers, respectively, used for diazene
      synthesis. This convergent and modular assembly of intact cyclotryptamines offers
      the first solution to access these alkaloids through completely stereoselective
      union of monomers at challenging linkages and the associated quaternary
      stereocenters as illustrated in our synthesis of five members of the
      oligocyclotryptamine family of alkaloids.

PMID- 29058432
TI  - Stereoselective Hydrolysis of Epoxides by reVrEH3, a Novel Vigna radiata Epoxide
      Hydrolase with High Enantioselectivity or High and Complementary
      Regioselectivity.
AB  - To provide more options for the stereoselective hydrolysis of epoxides, an
      epoxide hydrolase (VrEH3) gene from Vigna radiata was cloned and expressed in
      Escherichia coli. Recombinant VrEH3 displayed the maximum activity at pH 7.0 and
      45  degrees C and high stability at pH 4.5-7.5 and 55  degrees C. Notably,
      reVrEH3 exhibited high and complementary regioselectivity toward styrene oxides
      1a-3a and high enantioselectivity (E = 48.7) toward o-cresyl glycidyl ether 9a.
      To elucidate these interesting phenomena, the interactions of the three
      dimensional structure between VrEH3 and enantiomers of 1a and 9a were analyzed by
      molecular docking simulation. Using E. coli/vreh3 whole cells, gram-scale
      preparations of (R)-1b and (R)-9a were performed by enantioconvergent hydrolysis
      of 100 mM rac-1a and kinetic resolution of 200 mM rac-9a in the buffer-free water
      system at 25  degrees C. These afforded (R)-1b with >99% eep and 78.7% overall
      yield after recrystallization and (R)-9a with >99% ees, 38.7% overall yield, and
      12.7 g/L/h space-time yield.

PMID- 29058433
TI  - Effects of P25 TiO2 Nanoparticles on the Free Radical-Scavenging Ability of
      Antioxidants upon Their Exposure to Simulated Sunlight.
AB  - Although nanosized ingredients, including TiO2 nanoparticles (NPs), can be found
      in a wide range of consumer products, little is known about the effects these
      particles have on other active compounds in product matrices. These NPs can
      interact with reactive oxygen species (ROS), potentially disrupting or canceling
      the benefits expected from antioxidants. We used electron spin resonance
      spectrometry to assess changes in the antioxidant capacities of six dietary
      antioxidants (ascorbic acid, alpha-tocopherol, glutathione, cysteine,
      epicatechin, and epicatechin gallate) during exposure to P25 TiO2 and/or
      simulated sunlight. Specifically, we determined the ability of these antioxidants
      to scavenge 1-diphenyl-2-picryl-hydrazyl radical, superoxide radical, and
      hydroxyl radical. Exposure to simulated sunlight alone did not lead to noticeable
      changes in radical-scavenging abilities; however, in combination with P25 TiO2
      NPs, the scavenging abilities of most antioxidants were weakened. We found
      glutathione to be the most resistant to treatment with sunlight and NPs among
      these six antioxidants.

PMID- 29058434
TI  - Direct Determination of Six Cytokinin Nucleotide Monophosphates in Coconut Flesh
      by Reversed-Phase Liquid Chromatography-Tandem Mass Spectrometry.
AB  - Coconut contains many uncharacterized cytokinins that have important
      physiological effects in plants and humans. In this work, a method based on
      liquid chromatography-tandem mass spectrometry was developed for identification
      and quantification of six cytokinin nucleotide monophosphates in coconut flesh.
      Excellent separation was achieved using a low-coverage C18 bonded-phase column
      with an acidic mobile phase, which greatly improved the retention of target
      compounds. To enable high-throughput analysis, a single-step solid-phase
      extraction using mixed-mode anion-exchange cartridges was employed for sample
      preparation. This proved to be an effective method to minimize matrix effects and
      ensure high selectivity. The limits of detection varied from 0.06 to 0.3 ng/mL,
      and the limits of quantification ranged from 0.2 to 1.0 ng/mL. The linearity was
      statistically verified over 2 orders of magnitude, giving a coefficient of
      determination (R2) greater than 0.9981. The mean recoveries were from 81 to 108%;
      the intraday precision (n = 6) was less than 11%; and the interday precision (n =
      11) was within 14%. The developed method was applied to the determination of
      cytokinin nucleotide monophosphates in coconut flesh samples, and four of them
      were successfully identified and quantified. The results showed that trans-zeatin
      riboside-5'-monophosphate was the dominant cytokinin, with a concentration of 2.7
      34.2 ng/g, followed by N6-isopentenyladenosine-5'-monophosphate (<=12.9 ng/g),
      while the concentrations of cis-zeatin riboside-5'-monophosphate and
      dihydrozeatin riboside-5'-monophosphate were less than 2.2 and 4.9 ng/g,
      respectively.

PMID- 29058435
TI  - Efficient Hydrogen Evolution on Cu Nanodots-Decorated Ni3S2 Nanotubes by
      Optimizing Atomic Hydrogen Adsorption and Desorption.
AB  - Low-cost transition-metal dichalcogenides (MS2) have attracted great interest as
      alternative catalysts for hydrogen evolution. However, a significant challenge is
      the formation of sulfur-hydrogen bonds on MS2 (S-Hads), which will severely
      suppress hydrogen evolution reaction (HER). Here we report Cu nanodots (NDs)
      decorated Ni3S2 nanotubes (NTs) supported on carbon fibers (CFs) (Cu NDs/Ni3S2
      NTs-CFs) as efficient electrocatalysts for HER in alkaline media. The electronic
      interactions between Cu and Ni3S2 result in Cu NDs that are positively charged
      and can promote water adsorption and activation. Meanwhile, Ni3S2 NTs are
      negatively charged and can weaken S-Hads bonds formed on catalyst surfaces.
      Therefore, the Cu/Ni3S2 hybrids can optimize H adsorption and desorption on
      electrocatalysts and can promote both Volmer and Heyrovsky steps of HER. The
      strong interactions between Cu and Ni3S2 cause the Cu NDs/Ni3S2 NTs-CFs
      electrocatalysts to exhibit the outstanding HER catalytic performance with low
      onset potential, high catalytic activity, and excellent stability.

PMID- 29058436
TI  - Silicon Nanocrystal Superlattice Nucleation and Growth.
AB  - Colloidal dodecene-passivated silicon (Si) nanocrystals were dispersed in hexane
      or chloroform and deposited onto substrates as face-centered cubic superlattices
      by slowly evaporating the solvent. The uniformity of the nanocrystals enables
      extended order; however, the solvent and the evaporation protocol significantly
      influence the self-assembly process, determining the morphology of the films, the
      extent of order, and the superlattice orientation on the substrate. Chloroform
      yielded superlattices with step-flow growth morphologies and (111)SL, (100)SL,
      and (110)SL orientations. Hexane led to mostly island morphologies when
      evaporated at room temperature with exclusively (111)SL orientations. Higher
      evaporation temperatures led to more extensive step-flow deposition. A model for
      the surface diffusion of nanocrystals adsorbed on the superlattice surface is
      developed.

PMID- 29058437
TI  - Band Transport and Trapping in Didodecyl[1]benzothieno[3,2-b][1]benzothiophene
      Probed by Terahertz Spectroscopy.
AB  - Terahertz electromodulation spectroscopy provides insight into the material
      inherent transport properties of charge carriers in organic semiconductors.
      Experiments on didodecyl[1]benzothieno[3,2-b][1]benzothiophene (C12-BTBT-C12)
      devices yield for holes an intraband mobility of 9 cm2 V-1 s-1. The short
      duration of the THz pulses advances the understanding of the hole transport on
      the molecular scale. The efficient screening of Coulomb potentials leads to a
      collective response of the hole gas to external fields, which can be well
      described by the Drude model. Bias stress of the devices generates deep traps
      that capture mobile holes. Although the resulting polarization across the device
      hinders the injection of mobile holes, the hole mobilities are not affected.

PMID- 29058439
TI  - Rh(II)-Catalyzed Denitrogenative Reaction of N-Sulfonyl-1,2,3-triazoles with
      Isatins for the Construction of Indigoids.
AB  - A convenient, Rh(II)-catalyzed, denitrogenative reaction of N-sulfonyl-1,2,3
      triazoles and isatins to access (E)-2-(1-amino-2-oxo-2-phenylethylidene)indolin-3
      ones, the core structure of indigo dyes, was achieved under operationally simple
      conditions with high levels of diastereoselectivity. Moreover, photophysical and
      electrochemical studies were conducted to understand their applicability in
      optoelectronic applications.

PMID- 29058438
TI  - Self-Assembly of Fluorinated Sugar Amino Acid Derived alpha,gamma-Cyclic Peptides
      into Transmembrane Anion Transport.
AB  - Syntheses of fluorinated sugar amino acid derived alpha,gamma-cyclic tetra- and
      hexapeptides are reported. The IR, NMR, ESI-MS, CD, and molecular modeling
      studies of cyclic tetra- and hexapeptides showed C2 and C3 symmetric flat oval-
      and triangular-ring shaped beta-strand conformations, respectively, which appear
      to self-assemble into nanotubes. The alpha,gamma-cyclic hexapeptide (EC50 = 2.14
      MUM) is found to be a more efficient ion transporter than alpha,gamma-cyclic
      tetrapeptide (EC50 = 14.75 MUM). The anion selectivity and recognition of
      alpha,gamma-cyclic hexapeptide with NO3- ion is investigated.

PMID- 29058440
TI  - Direct Amplitude-Phase Near-Field Observation of Higher-Order Anapole States.
AB  - Anapole states associated with the resonant suppression of electric-dipole
      scattering exhibit minimized extinction and maximized storage of electromagnetic
      energy inside a particle. Using numerical simulations, optical extinction
      spectroscopy, and amplitude-phase near-field mapping of silicon dielectric disks,
      we demonstrate high-order anapole states in the near-infrared wavelength range
      (900-1700 nm). We develop the procedure for unambiguously identifying anapole
      states by monitoring the normal component of the electric near-field and
      experimentally detect the first two anapole states as verified by far-field
      extinction spectroscopy and confirmed with the numerical simulations. We
      demonstrate that higher-order anapole states possess stronger energy
      concentration and narrower resonances, a remarkable feature that is advantageous
      for their applications in metasurfaces and nanophotonics components, such as
      nonlinear higher-harmonic generators and nanoscale lasers.

PMID- 29058441
TI  - Acid-Group-Content-Dependent Proton Conductivity Mechanisms at the Interlayer of
      Poly(N-dodecylacrylamide-co-acrylic acid) Copolymer Multilayer Nanosheet Films.
AB  - The effect of the content of acid groups on the proton conductivity at the
      interlayer of polymer-nanosheet assemblies was investigated. For that purpose,
      amphiphilic poly(N-dodecylacrylamide-co-acrylic acid) copolymers [p(DDA/AA)] with
      varying contents of AA were synthesized by free radical polymerization. Surface
      pressure (pi)-area (A) isotherms of these copolymers indicated that stable
      polymer monolayers are formed at the air/water interface for AA mole fraction (n)
      <= 0.49. In all cases, a uniform dispersion of the AA groups in the polymer
      monolayer was observed. Subsequently, polymer monolayers were transferred onto
      solid substrates using the Langmuir-Blodgett (LB) technique. X-ray diffraction
      (XRD) analyses of the multilayer films showed strong Bragg diffraction peaks,
      suggesting a highly uniform lamellar structure for the multilayer films. The
      proton conductivity of the multilayer films parallel to the direction of the
      layer planes were measured by impedance spectroscopy, which revealed that the
      conductivity increased with increasing values of n. Activation energies for
      proton conduction of ~0.3 and 0.42 eV were observed for n >= 0.32 and n = 0.07,
      respectively. Interestingly, the proton conductivity of a multilayer film with n
      = 0.19 did not follow the Arrhenius equation. These results were interpreted in
      terms of the average distance between the AA groups (lAA), and it was concluded
      that, for n >= 0.32, an advanced 2D hydrogen bonding network was formed, while
      for n = 0.07, lAA is too long to form such hydrogen bonding networks. The lAA for
      n = 0.19 is intermediate to these extremes, resulting in the formation of
      hydrogen bonding networks at low temperatures, and disruption of these networks
      at high temperatures due to thermally induced motion. These results indicate that
      a high proton conductivity with low activation energy can be achieved, even under
      weakly acidic conditions, by arranging the acid groups at an optimal distance.

PMID- 29058442
TI  - Non-Faradaic Li+ Migration and Chemical Coordination across Solid-State Battery
      Interfaces.
AB  - Efficient and reversible charge transfer is essential to realizing high
      performance solid-state batteries. Efforts to enhance charge transfer at critical
      electrode-electrolyte interfaces have proven successful, yet interfacial
      chemistry and its impact on cell function remains poorly understood. Using X-ray
      photoelectron spectroscopy combined with electrochemical techniques, we elucidate
      chemical coordination near the LiCoO2-LIPON interface, providing experimental
      validation of space-charge separation. Space-charge layers, defined by local
      enrichment and depletion of charges, have previously been theorized and modeled,
      but the unique chemistry of solid-state battery interfaces is now revealed. Here
      we highlight the non-Faradaic migration of Li+ ions from the electrode to the
      electrolyte, which reduces reversible cathodic capacity by ~15%. Inserting a
      thin, ion-conducting LiNbO3 interlayer between the electrode and electrolyte,
      however, can reduce space-charge separation, mitigate the loss of Li+ from
      LiCoO2, and return cathodic capacity to its theoretical value. This work
      illustrates the importance of interfacial chemistry in understanding and
      improving solid-state batteries.

PMID- 29058445
TI  - Future of Nano Letters Early Career Board.

PMID- 29058443
TI  - Enhanced Triggering of Local Anesthetic Particles by Photosensitization and
      Photothermal Effect Using a Common Wavelength.
AB  - On-demand pain relief systems would be very helpful additions to the
      armamentarium of pain management. Near-infrared triggered drug delivery systems
      have demonstrated the potential to provide such care. However, challenges remain
      in making such systems as stimulus-sensitive as possible, to enhance depth of
      tissue penetration, repeatability of triggering, and safety. Here we developed
      liposomes containing the local anesthetic tetrodotoxin and also containing a
      photosensitizer and gold nanorods that were excitable at the same near-infrared
      wavelength. The combination of triggering mechanisms enhanced the
      photosensitivity and repeatability of the system in vitro when compared with
      liposomes with a single photoresponsive component. In vivo, on-demand local
      anesthesia could be induced with a low irradiance and short irradiation duration,
      and liposomes containing both photosensitizer and gold nanorods were more
      effective than those containing just one photoresponsive component. Tissue
      reaction was benign.

PMID- 29058444
TI  - Combining in Vitro and in Silico Single-Molecule Force Spectroscopy to
      Characterize and Tune Cellulosomal Scaffoldin Mechanics.
AB  - Cellulosomes are polyprotein machineries that efficiently degrade cellulosic
      material. Crucial to their function are scaffolds consisting of highly homologous
      cohesin domains, which serve a dual role by coordinating a multiplicity of
      enzymes as well as anchoring the microbe to its substrate. Here we combined two
      approaches to elucidate the mechanical properties of the main scaffold ScaA of
      Acetivibrio cellulolyticus. A newly developed parallelized one-pot in vitro
      transcription-translation and protein pull-down protocol enabled high-throughput
      atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS)
      measurements of all cohesins from ScaA with a single cantilever, thus promising
      improved relative force comparability. Albeit very similar in sequence, the
      hanging cohesins showed considerably lower unfolding forces than the bridging
      cohesins, which are subjected to force when the microbe is anchored to its
      substrate. Additionally, all-atom steered molecular dynamics (SMD) simulations on
      homology models offered insight into the process of cohesin unfolding under
      force. Based on the differences among the individual force propagation pathways
      and their associated correlation communities, we designed mutants to tune the
      mechanical stability of the weakest hanging cohesin. The proposed mutants were
      tested in a second high-throughput AFM SMFS experiment revealing that in one case
      a single alanine to glycine point mutation suffices to more than double the
      mechanical stability. In summary, we have successfully characterized the force
      induced unfolding behavior of all cohesins from the scaffoldin ScaA, as well as
      revealed how small changes in sequence can have large effects on force resilience
      in cohesin domains. Our strategy provides an efficient way to test and improve
      the mechanical integrity of protein domains in general.

PMID- 29058446
TI  - Nanotube Alignment Mechanism in Floating Evaporative Self-Assembly.
AB  - The challenge of assembling semiconducting single-wall carbon nanotubes (s
      SWCNTs) into densely packed, aligned arrays has limited the scalability and
      practicality of high-performance nanotube-based electronics technologies. The
      aligned deposition of s-SWCNTs via floating evaporative self-assembly (FESA) has
      promise for overcoming this challenge; however, the mechanisms behind FESA need
      to be elucidated before the technique can be improved and scaled. Here, we gain a
      deeper understanding of the FESA process by studying a stationary analogue of
      FESA and optically tracking the dynamics of the organic ink/water/substrate and
      ink/air/substrate interfaces during the typical FESA process. We observe that the
      ink/water interface serves to collect and confine the s-SWCNTs before alignment
      and that the deposition of aligned bands of s-SWCNTs occurs at the
      ink/water/substrate contact line during the depinning of both the
      ink/air/substrate and ink/water/substrate contact lines. We also demonstrate
      improved control over the interband spacing, bandwidth, and packing density of
      FESA-aligned s-SWCNT arrays. The substrate lift rate (5-15 mm min-1) is used to
      tailor the interband spacing from 90 to 280 MUm while maintaining a constant
      aligned s-SWCNT bandwidth of 50 MUm. Varying the s-SWCNT ink concentration (0.75
      10 MUg mL-1) allows the control of the bandwidth from 2.5 to 45 MUm. A steep
      increase in packing density is observed from 11 s-SWCNTs MUm-1 at 0.75 MUg mL-1
      to 20 s-SWCNTs MUm-1 at 2 MUg mL-1, with a saturated packing density of ~24 s
      SWCNTs MUm-1. We also demonstrate the scaling of FESA to align s-SWCNTs on a 2.5
      * 2.5 cm2 scale while preserving high-quality alignment on the nanometer scale.
      These findings help realize the scalable fabrication of well-aligned s-SWCNT
      arrays to serve as large-area platforms for next-generation semiconductor
      electronics.

PMID- 29058447
TI  - Detection and Characterization of Hydride Ligands in Iron Complexes by High
      Resolution Hard X-ray Spectroscopy and Implications for Catalytic Processes.
AB  - Two hydride catalysts [Fe(CO)(dppp)H(NO)] (dppp = 1,3
      bis(diphenylphosphino)propane) and [Fe(CO)H(NO)(PPh3)2] in comparison with
      nonhydride analogues [Fe(dppe)(NO)2] (dppe = 1,3-bis(diphenylphosphino)ethane)
      and [Fe(NO)2(PPh3)2] are investigated with a combination of valence-to-core X-ray
      emission spectroscopy (VtC-XES) and high-energy resolution fluorescence detected
      X-ray absorption near-edge structure (HERFD-XANES). To fully understand the
      experiments and to obtain precise information about molecular levels being
      involved in the spectral signals, time-dependent density functional theory (TD
      DFT) calculations and ground state density functional theory (DFT) calculations
      are necessary. An excellent agreement between experiment and theory allows the
      identification of particular spectral signals of the Fe-H group. Antibonding Fe-H
      interactions clearly contribute to pre-edge signals in HERFD-XANES spectra, while
      bonding Fe-H interactions cause characteristic signatures in the VtC-XES spectra.
      The sensitivity of both methods with respect to the Fe-H distance is demonstrated
      by a scanning simulation approach. The results open the way to study metal
      hydride complexes in situ, their formation, and their fate during catalytic
      reactions, using high-resolution XANES and valence-to-core X-ray emission
      spectroscopy.

PMID- 29058448
TI  - Improving Care for Patients with Interstitial Lung Disease Using Machine Learning
      Requires Transparency and Reproducibility.

PMID- 29058449
TI  - Response to Ward et al. re: "ABM Clinical Protocol #3: Supplementary Feedings in
      the Healthy Term Breastfed Neonate, Revised 2017".

PMID- 29058450
TI  - Range of Motion of the First Metatarsophalangeal Joint after Different
      Capsulorrhaphies: A Comparative Cadaver Study.
AB  - BACKGROUND: Capsulorrhaphy restricts the motion of the first metatarsophalangeal
      joint (1st MTPJ) in hallux valgus surgery. However, changes in motion of the
      first MTPJ immediately after surgery that resulted from different capsulorrhaphy
      methods have not been compared. The primary aim of this study was to compare the
      immediate effect of Y-shaped and inverted L capsulorrhaphy methods on the range
      of motion (ROM) of the 1st MTPJ. METHODS: Y-shaped and inverted L
      capsulorrhaphies were performed on sixteen human cadaveric feet. Passive
      dorsiflexion (DF) and plantarflexion (PF) of the 1st MTPJ were then compared pre
      and postoperatively. RESULTS: In the current cadaveric study, the inverted L
      capsulorrhaphy methods can lead to a ROM loss in the first MTPJ; the joint
      stiffness from the Y-shaped capsulorrhaphy is significantly less than the
      inverted L capsulorrhaphy. CONCLUSIONS: The inverted L capsulorrhaphy may lead to
      a ROM loss of the 1st MTPJ immediately after surgery. We recommend surgeons close
      the capsule of the 1st MTPJ with Y-shaped capsulorrhaphy, which is less likely to
      result in a ROM loss in the first MTPJ in early postoperative period.

PMID- 29058451
TI  - Reply: Improving Care for Patients with Interstitial Lung Disease, Using Machine
      Learning, Requires Transparency and Reproducibility.

PMID- 29058452
TI  - Investigation of the Geochemical Preservation of ca. 3.0 Ga Permineralized and
      Encapsulated Microfossils by Nanoscale Secondary Ion Mass Spectrometry.
AB  - Observations of Archean organic-walled microfossils suggest that their
      fossilization took place through both encapsulation and permineralization. In
      this study, we investigated microfossils from the ca. 3.0 Ga Farrel Quartzite
      (Pilbara, Western Australia) using transmitted light microscopy, scanning
      electron microscopy, Raman microspectrometry, and nanoscale secondary ion mass
      spectrometry (NanoSIMS) ion microprobe analyses. In contrast to previous studies,
      we demonstrated that permineralized microfossils were not characterized by the
      micrometric spatial relationships between Si and C-N as observed in thin
      sections. Permineralized microfossils are composed of carbonaceous globules that
      did not survive the acid treatment, whereas encapsulated microfossils were
      characterized due to their resistance to the acid maceration procedure. We also
      investigated the microscale relationship between the 12C14N- and 12C2- ion
      emission as a proxy of the N/C atomic ratio in both permineralized and
      encapsulated microfossils. After considering any potential matrix and
      microtopography effects, we demonstrate that the encapsulated microfossils
      exhibit the highest level of geochemical preservation. This finding shows that
      the chemical heterogeneity of the microfossils, observed at a spatial resolution
      of a few hundreds of micrometers, can be related to fossilization processes. Key
      Words: Carbonaceous matter-Farrel Quartzite-Fossilization-NanoSIMS-Nitrogen
      Permineralization. Astrobiology 17, 1192-1202.

PMID- 29058453
TI  - Long-Term Acupuncture Therapy for Low-Income Older Adults with Multimorbidity: A
      Qualitative Study of Patient Perceptions.
AB  - OBJECTIVES: Multimorbidity is common, but often poorly managed, among the rapidly
      growing population of older adults. The existing guidelines followed by
      physicians frequently lead to polypharmacy and a complex treatment burden. The
      objective of this study was to explore what benefits are perceived by older
      adults with multimorbidity as a result of long-term, regular acupuncture
      treatment. DESIGN: A qualitative design with inductive thematic analysis of
      semistructured interviews. SETTINGS/LOCATION: Participants were recruited from a
      no-cost, college-affiliated acupuncture clinic for low-income older adults in an
      urban, racially/ethnically diverse neighborhood in southern California.
      PARTICIPANTS: Fifteen patients aged 60 years and older suffering from at least
      two chronic conditions. RESULTS: Five themes were identified: (1) mind-body
      effects, (2) the enhanced therapeutic alliance, (3) what they liked best, (4) the
      conventional healthcare system, and (5) importance of regular schedule. A notable
      mind-body effect, reported by a substantial number of participants, was
      medication reduction. Participants also cited changes in mood, energy, and well
      being as important benefits. In addition, they voiced widespread dissatisfaction
      with conventional healthcare. Keeping up regular treatments as a way to deal with
      new complaints and encourage a healthier lifestyle was seen an important aspect
      of care at the clinic. CONCLUSIONS: This cohort of older adults with
      multimorbidity valued acupuncture as a way to reduce medication as well as a
      means to maintain physical and mental health. In addition, they developed a
      strong trust in the clinic's ability to support the totality of their health as
      individuals, which they contrasted to the specialized and impersonal approach of
      the conventional medical clinic.

PMID- 29058454
TI  - Anti-bacterial and anti-biofilm activity of commercial organic acid products
      against Salmonella enterica isolates recovered from an egg farm environment.
AB  - This study evaluated the antibacterial activity of commercially available organic
      acid water additives against Salmonella enterica isolates and examined the
      susceptibility of Salmonella Typhimurium biofilms to these products. Three
      commercial organic acid products (A, B, and C) were evaluated for minimum
      inhibitory and bactericidal concentrations against isolates of S. enterica
      serovars. Three- and five-day-old S. Typhimurium biofilms were formed at 22 +/- 2
      degrees C using an MBECTM assay system and exposed for 30 min or 90 min at 0.2%
      and 0.4% concentrations. No significant difference among serovars for inhibitory
      and bactericidal concentrations was detected. Two products (A and C)
      significantly reduced viable cells from biofilms of both ages in a dose- and time
      dependent manner. Increased biofilm age did not enhance resistance towards
      organic acid treatments. None of the products completely eliminated biofilm cells
      at any concentration or exposure time. Product composition, exposure time, and
      concentration of organic acid products were important factors in reducing viable
      biofilm cells. This study has expanded our understanding about the susceptibility
      of Salmonella biofilms to commercial organic acid products. These findings have
      implications in the usage, development, and optimization of organic acid
      products.

PMID- 29058455
TI  - Newborn Neurons Are Damaged In Vitro by a Low Concentration of Silver
      Nanoparticles Through the Inflammatory Oxidative Stress Pathway.
AB  - With increasing applications of nanomaterials, including silver nanoparticles
      (AgNPs), unknown potential risks are present against humans and the environment,
      especially to the fetus and neonates, which are more sensitive to the
      cytotoxicity of such agents. This study focused on the effects of AgNP exposure
      on newborn neurons differentiated from neural stem cells (NSCs) in vitro. We
      isolated NSCs from fetal rat hippocampus and incubated them in neural
      differentiation medium for 3-7 days to form newborn neurons and networks. After
      exposure to 2 MUg/mL AgNPs, cell viability was reduced, and early neuronal
      processes and extensions were fragmented. Furthermore, AgNP treatment increased
      cellular superoxide dismutase activity and decreased the mitochondrial membrane
      potential, leading to neuronal death. AgNPs also increased the expression of
      FOXO3 and decreased nuclear factor-erythroid 2-related factor-2, as well as
      stimulated the formation of autophagosomes. Therefore, even a low concentration
      of AgNPs can interrupt early neuronal processes, and facilitate neuron apoptosis
      by increased cellular oxidative stress and mitochondrial disruption. Thus, it is
      necessary to note the daily exposure of nanomaterials (e.g., AgNPs) to pregnant
      women and infants, which may cause neurodevelopmental disorders.

PMID- 29058456
TI  - Cholera control and anti-Haitian stigma in the Dominican Republic: from migration
      policy to lived experience.
AB  - As cholera spread from Haiti to the Dominican Republic, Haitian migrants, a
      largely undocumented and stigmatized population in Dominican society, became a
      focus of public health concern. Concurrent to the epidemic, the Dominican
      legislature enacted new documentation requirements. This paper presents findings
      from an ethnographic study of anti-Haitian stigma in the Dominican Republic from
      June to August 2012. Eight focus group discussions (FGDs) were held with Haitian
      and Dominican community members. Five in-depth interviews were held with key
      informants in the migration policy sector. Theoretical frameworks of stigma's
      moral experience guided the analysis of how cholera was perceived, ways in which
      blame was assigned and felt and the relationship between documentation and
      healthcare access. In FGDs, both Haitians and Dominicans expressed fear of
      cholera and underscored the importance of public health messages to prevent the
      epidemic's spread. However, health messages also figured into experiences of
      stigma and rationales for blame. For Dominicans, failure to follow public health
      advice justified the blame of Haitians and seemed to confirm anti-Haitian
      sentiments. Haitians communicated a sense of powerlessness to follow public
      health messages given structural constraints like lack of safe water and
      sanitation, difficulty accessing healthcare and lack of documentation. In effect,
      by making documentation more difficult to obtain, the migration policy undermined
      cholera programs and contributed to ongoing processes of moral disqualification.
      Efforts to eliminate cholera from the island should consider how policy and
      stigma can undermine public health campaigns and further jeopardize the everyday
      'being-in-the-world' of vulnerable groups.

PMID- 29058457
TI  - Community outreach programs and major adherence lapses with antiretroviral
      therapy in rural Kakamega, Kenya.
AB  - We investigated features of major adherence lapses in antiretroviral therapy
      (ART) at public Emusanda Health Centre in rural Kakamega County, Kenya using
      medical records from 2008 to 2015 for all 306 eligible patients receiving ART.
      Data were modelled using survival analysis. Patients were more likely to lapse if
      they received stavudine (hazard ratio (HR) 2.54, 95% confidence interval
      (95%CI):1.44-4.47) or zidovudine (HR 1.64, 95%CI:1.02-2.63) relative to
      tenofovir. Each day a patient slept hungry per month increased risk of major
      adherence lapse by 3% (95%CI:0-7%). Isolated home visits by community health
      workers (CHWs) were more effective to assist patients to return to the health
      centre than isolated phone calls (HR 2.52, 95%CI:1.02-6.20).

PMID- 29058458
TI  - Clemochinenosides C and D, two new macrocyclic glucosides from Clematis
      chinensis.
AB  - The EtOH extract of the roots and rhizomes of Clematis chinensis afforded two new
      macrocyclic glucosides clemochinenosides C (1) and D (2). Their structures were
      elucidated on the basis of spectroscopic means and hydrolysis products. These
      compounds were evaluated for inhibitory activity against lipopolysaccharides
      induced TNF-alpha production in RAW 246.7 macrophages. Compounds 1 and 2 showed
      moderate inhibitory activity with IC50 values of 12.9 +/- 2.3 and 18.4 +/- 2.7
      MUM, respectively. In addition, a proliferation study was used to evaluate the
      anti-angiogenic effects of these compounds in vitro (VEGF-induced human umbilical
      vein endothelial cell proliferation). Compounds 1 and 2 displayed weak inhibitory
      effects with inhibition rates of 26.3 +/- 1.8 and 19.2 +/- 2.6% at 50 MUM,
      respectively.

PMID- 29058459
TI  - Secondary collisions and injury severity: A joint analysis using structural
      equation models.
AB  - OBJECTIVE: This study aims to investigate the contributing factors to secondary
      collisions and the effects of secondary collisions on injury severity levels.
      Manhattan, which is the most densely populated urban area of New York City, is
      used as a case study. In Manhattan, about 7.5% of crash events become involved
      with secondary collisions and as high as 9.3% of those secondary collisions lead
      to incapacitating and fatal injuries. METHODS: Structural equation models (SEMs)
      are proposed to jointly model the presence of secondary collisions and injury
      severity levels and adjust for the endogeneity effects. The structural
      relationship among secondary collisions, injury severity, and contributing
      factors such as speeding, alcohol, fatigue, brake defects, limited view, and rain
      are fully explored using SEMs. In addition, to assess the temporal effects, we
      use time as a moderator in the proposed SEM framework. RESULTS: Due to its better
      performance compared with other models, the SEM with no constraint is used to
      investigate the contributing factors to secondary collisions. Thirteen
      explanatory variables are found to contribute to the presence of secondary
      collisions, including alcohol, drugs, inattention, inexperience, sleep, control
      disregarded, speeding, fatigue, defective brakes, pedestrian involved, defective
      pavement, limited view, and rain. Regarding the temporal effects, results
      indicate that it is more likely to sustain secondary collisions and severe
      injuries at night. CONCLUSIONS: This study fully investigates the contributing
      factors to secondary collisions and estimates the safety effects of secondary
      collisions after adjusting for the endogeneity effects and shows the advantage of
      using SEMs in exploring the structural relationship between risk factors and
      safety indicators. Understanding the causes and impacts of secondary collisions
      can help transportation agencies and automobile manufacturers develop effective
      injury prevention countermeasures.

PMID- 29058460
TI  - Ginsenoside Rg1 Activates Dendritic Cells and Acts as a Vaccine Adjuvant Inducing
      Protective Cellular Responses Against Lymphomas.
AB  - Ginsenoside, a natural triterpenoid saponin, exhibits immunomodulatory and
      anticancer activities. In the present study, we demonstrated that ginsenoside Rg1
      induced secretion of cytokines, including interleukin (IL)-6, tumor necrosis
      factor-alpha (TNF-alpha), and IL-1beta, and chemokines such as IL-8 and IP-10 in
      a dose-dependent manner by human peripheral blood mononuclear cell (PBMC)-derived
      dendritic cells. Rg1 stimulated the expression of the surface molecules CD83,
      CD80, and human leukocyte antigen - antigen D related (HLA-DR) and decreased the
      expression of CD14. In in vivo experiments, C57BL/6 mice were divided into four
      groups, immunized with ovalbumin (OVA), OVA plus Rg1, Rg1, and phosphate-buffered
      saline (PBS), respectively. Splenocytes from C57BL/6 mice immunized with OVA plus
      Rg1 produced more antigen-specific splenocyte proliferation activity. The level
      of IFN-gamma and IL-4 in the splenocytes was also upregulated when in vitro
      stimulated with OVA257-264 or OVA. After in vivo injection of tumor-forming E.G7
      OVA cells, the survival rate of mice immunized intraperitoneally in OVA plus Rg1
      immunized mice was higher than that in OVA immunized mice or PBS immunized mice.
      Thus, Rg1 induced a potent vaccine adjuvant effect and elicited antitumor
      immunity that polarized a Th1 type immune response. Rg1 could have potential as a
      prophylactic vaccine adjuvant to control lymphomas.

PMID- 29058461
TI  - Caregiver role in HIV medication adherence among HIV-infected orphans in
      Tanzania.
AB  - Youth living with HIV in sub-Saharan Africa face numerous challenges in adhering
      to HIV treatment. The AIDS epidemic has left many of these youth orphaned due to
      AIDS-related death of one or both parents. It is imperative to understand the
      family context of youth living with HIV in order to develop responsive
      interventions to improve adherence to antiretroviral therapy. We conducted
      qualitative in-depth interviews with 17 HIV-infected AIDS orphans, ages 13-24
      years, screened positive for mental health difficulties according to the Patient
      Health Questionaire-9 (PHQ-9) or UCLA PTSD Reaction Index (PTSD-RI), and
      receiving outpatient HIV care at an adolescent medical clinic in Moshi, Tanzania.
      Treatment-related support varied by orphan status. Paternal orphans cared for by
      their biological mothers and maternal orphans cared for by grandmothers described
      adherence support such as assistance taking medication and attending clinic.
      Double orphans did not report adherence support. Several maternal and double
      orphans faced direct interference from caregivers and household members when they
      attempted to take their medications. Caregivers play a significant role in
      treatment adherence and must be considered in interventions to increase
      medication adherence in HIV-infected orphans. Findings from this study informed
      caregiver participation in Sauti ya Vijana (The Voice of Youth), a mental health
      intervention for youth living with HIV in Tanzania.

PMID- 29058462
TI  - The effect of eubiotic feed additives on the performance of growing pigs and the
      activity of intestinal microflora.
AB  - The aim of this study was to compare the effect of probiotic bacteria,
      prebiotics, phytobiotics and their combinations on performance and microbial
      activity in the digestive tract of growing pigs. The experiment was conducted
      over 28 d on 48 male pigs of about 12 kg body weight (BW), which were allocated
      to following treatments.: (1) Control Group (Con) without additive, (2) Group I,
      addition of a prebiotic (inulin), (3) Group Ph, a phytobiotic (herbal water
      extracts), (4) Group P, a probiotic composed of four strains of lactic acid
      bacteria, (5) Group PhP, phytobiotic and probiotic bacteria and (6) Group PhPI, a
      phytobiotic, probiotic bacteria and a prebiotic. Animal performance was recorded
      and at d 28 six pigs from each group were euthanised to collect digesta samples.
      In all groups except for Group I, diarrhoea incidents were observed. Groups Ph
      and P had significantly higher daily gains and final BW, and Group Ph utilised
      feed better than other groups. The pH of ileal digesta was significantly lower in
      Group PhPI. In the caecal digesta of Groups I, P and PhP, the pH level was lower
      than in the other groups but dry matter contents was significantly higher in
      Groups Con and I. The short-chain fatty acids and particular acid content
      differed significantly only in the colonic digesta. The yeast and mould numbers
      in caecal digesta was highest in Group Con. No treatment effects were observed
      for the number of lactic acid bacteria, coli group bacteria or Clostridium.
      However, the observed significantly higher number of total bacteria suggests that
      a multi-component eubiotic treatment changes the bacterial composition and
      distribution more effectively. Our findings indicated that all used additives
      changed the intestinal microflora, but the multi-component eubiotics were not
      beneficial as feed additives offered separately. Moreover, supplementation of
      phytobiotics and probiotic bacteria also improved the animal performance
      significantly.

PMID- 29058463
TI  - Genetic Analysis of Dent's Disease and Functional Research of CLCN5 Mutations.
AB  - Dent's disease is an X-linked inherited renal disease. Patients with Dent's
      disease often carry mutations in genes encoding the Cl-/H+ exchanger ClC-5 and/or
      inositol polyphosphate 5-phosphatase (OCRL1). However, the mutations involved and
      the biochemical effects of these mutations are not fully understood. To
      characterize genetic changes in Dent's disease patients, in this study, samples
      from nine Chinese patients were subjected to genetic analysis. Among the nine
      patients, six were classified as having Dent-1 disease, one had Dent-2 disease,
      and two could not be classified. Expression of ClC-5 carrying Dent's disease
      associated mutations in HEK293 cells had varying effects: (1) no detectable
      expression of mutant protein; (2) retention of a truncated protein in the
      endoplasmic reticulum; or (3) diminished protein expression with normal
      distribution in early endosomes. Dent's disease patients showed genetic
      heterogeneity and over 20% of patients did not have CLCN5 or OCRL1 mutations,
      suggesting the existence of other genetic factors. Using next-generation
      sequencing, we identified possible modifier genes that have not been previously
      reported in Dent's disease patients. Heterozygous variants in CFTR, SCNN1A, and
      SCNN1B genes associated with cystic fibrosis (CF) or CF-like disease were
      detected in four of our nine patients. These results may form the basis for
      future characterization of Dent's disease and genetic counseling approaches.

PMID- 29058464
TI  - Prediction of Central Nervous System Side Effects Through Drug Permeability to
      Blood-Brain Barrier and Recommendation Algorithm.
AB  - Drug side effects are one of the public health concerns. Using powerful machine
      learning methods to predict potential side effects before the drugs reach the
      clinical stages is of great importance to reduce time consumption and protect the
      security of patients. Recently, researchers have proved that the central nervous
      system (CNS) side effects of a drug are closely related to its permeability to
      the blood-brain barrier (BBB). Inspired by this, we proposed an extended
      neighborhood-based recommendation method to predict CNS side effects using drug
      permeability to the BBB and other known features of drug. To the best of our
      knowledge, this is the first attempt to predict CNS side effects considering drug
      permeability to the BBB. Computational experiments demonstrated that drug
      permeability to the BBB is an important factor in CNS side effects prediction.
      Moreover, we built an ensemble recommendation model and obtained higher AUC score
      (area under the receiver operating characteristic curve) and AUPR score (area
      under the precision-recall curve) on the data set of CNS side effects by
      integrating various features of drug.

PMID- 29058465
TI  - Positional synchronization affects physical and physiological responses to
      preseason in professional football (soccer).
AB  - This study aimed to identify changes in tactical, physical and physiological
      performances in large-sided games during the preseason of elite footballers.
      Thirty professional football players participated in several GK+8vs.8+GK large
      sided games across the first four weeks of the season. Players were monitored by
      GPS units and heart rate monitors to quantify physical, physiological and
      tactical performances. The variables were compared according to the preseason
      period, players' positioning and professional experience. The training situation
      promoted similar physiological responses during the first and the last training
      period. However, players were revealed to have higher levels of positional
      synchronization during the last preseason period, indicating an improved tactical
      performance. Tactical variables seem to reflect the improvement of players'
      performance during the preseason, measured in large-sided games situation, while
      affecting both physical and physiological demands. These results highlight the
      potential of positioning derived variables, concurrently to physical and
      physiological variables, for football training optimization.

PMID- 29058466
TI  - Changes in cardiac and muscle biomarkers following an uphill-only marathon.
AB  - The aim of the study was to evaluate changes in cardiac troponin I levels (cTnI)
      and the main biomarkers of skeletal muscle damage after an uphill-only marathon,
      along with its relationship with athletes' physiological parameters. Twenty-two
      runners participated in the "Supermaratona dell'Etna" (43 km, 0-2850 m AMSL).
      Before and immediately after the race, body mass and hydration status were
      measured together with blood sampling. At the end of the race, mean cTnI
      increased significantly in all athletes (mean +900%), and in 52% of them the cTnI
      values were over the normal range. Mean creatinine and cortisol increased
      significantly (by 30.5% and 291.4%), while C-reactive protein levels did not
      change significantly. Then, an uphill-only marathon showed a significant increase
      in cardiac and skeletal muscle blood biomarkers of injury, and cTnI levels were
      not significantly correlated with age, body mass index, VO2max, training status,
      ultra-endurance training experience, race time and blood parameters.

PMID- 29058467
TI  - Utility of matrix reasoning as an embedded performance validity indicator in
      pediatric mild traumatic brain injury.
AB  - The present study examined the utility of the Wechsler Abbreviated Scale of
      Intelligence, Second Edition (WASI-II) Matrix Reasoning (MR) subtest in detecting
      suspect effort among a pediatric mild traumatic brain injury (mTBI) sample. The
      sample consisted of 526 clinically referred patients aged 8-16 years. Sixteen
      percent of participants failed the Medical Symptom Validity Test, which was used
      to categorize the sample into adequate and suspect effort groups. No background
      or injury-related variables differentiated the two groups. Comparisons between
      the adequate and suspect effort groups revealed significant differences in MR
      performance (p < .001; d = 1.46). A subsample (n = 206) where first item missed
      data were available was also analyzed; suspect effort participants missed their
      first item significantly earlier than adequate effort participants. In the entire
      sample, a MR cutoff T-score of 43 resulted in sensitivity of 57% and specificity
      of 90%. Receiver operating characteristic area under the curve for MR T-score was
      .804. Within this relatively high-functioning pediatric population with mTBI, MR
      appeared to have good utility as an embedded validity indicator, with
      classification statistics comparable to many of the most commonly used embedded
      indices used with adults.

PMID- 29058469
TI  - Preliminary validation study of the Sydney Post-Traumatic Amnesia Scale (SYPTAS)
      in children with traumatic brain injury aged 4 to 7 years.
AB  - The aim of this study was to assess the validity (developmental, concurrent, and
      predictive) of the Sydney Post-Traumatic Amnesia Scale (SYPTAS) for assessment of
      post-traumatic amnesia (PTA) in 4 to 7 year old children with traumatic brain
      injury (TBI). The design of this study is a retrospective cohort study. The
      SYPTAS was administered to 35 children (26 boys) aged 4.0 to 7.8 years who were
      consecutively admitted to a children's hospital with mild (n = 26), moderate (n =
      3), or severe (n = 7) TBI. Concurrent validity of the SYPTAS was assessed against
      the Glasgow Coma Scale Scores (GCS). Predictive validity of the SYPTAS for
      functional outcomes was evaluated against the King's Outcome Scale for Childhood
      Head Injury (KOSCHI) at discharge and outpatient follow-ups. The length of PTA,
      measured by the SYPTAS, was invariant of children's chronological age, confirming
      the scale's developmental validity. Longer PTA was associated with lower GCS,
      endorsing concurrent validity of PTA duration measured by the SYPTAS, as a
      clinical indicator of TBI severity. PTA duration measured by the SYPTAS was a
      significant predictor of functional outcomes on the KOSCHI at discharge and
      follow-ups. This study provides evidence that the SYPTAS has good developmental,
      concurrent and predictive validity for assessment of PTA in children aged 4 to 7
      years. PTA duration assessed by the SYPTAS is a clinical indicator of TBI
      severity and can aid rehabilitation planning post TBI.

PMID- 29058468
TI  - Screening and identification of major phytochemical compounds in seeds, sprouts
      and leaves of Tuscan black kale Brassica oleracea (L.) ssp acephala (DC) var.
      sabellica L.
AB  - We report the spectrophotometric determination of total polyphenols, flavonoids,
      glucosinolates and antioxidant activity in seeds, seedlings and leaves of Tuscan
      black kale. The highest content of phytochemicals was observed in 10 days sprouts
      and antioxidant activity was maximum in 2, 4 days seedlings. Identification and
      characterisation of phytochemicals were performed by mass spectrometry (MS), high
      resolution and tandem MS with electrospray ionisation mode. Low-molecular-weight
      metabolites were evidenced in seeds while metabolites at high m/z range were
      detected in cotyledons and leaves. MS spectra evidenced different phenolic
      compounds (flavonoid caffeoyl glucose, hydroxycinnamic acid sinapine) and
      glucosinolates (glucoerucin, glucobrassicin and glucoraphanin) in function of
      developmental stage; galactolipids omega3 and omega6 were observed in leaves.
      Identification of stages with the highest phytochemicals content encourages the
      consumption of black kale sprouts and young leaves. Our research can support food
      and pharmaceutical industries for production of health promoting products from
      black kale.

PMID- 29058470
TI  - Combined visual and dribbling performance in young soccer players of different
      expertise.
AB  - We aimed to evaluate dribbling performance in terms of technique and visual
      skills assessment of both young experienced (EX, n = 24) and novice (NO, n = 24)
      soccer players. Both groups performed two dribbling tests with four levels of
      difficulty in visual signals (A1-A4 and B1-B4; B - half distance of A; 1 - no
      visual signal; 4 - signal with the shorter flashing time). All players performed
      slower when visual signals were added to the testing process (~2.5 s; p < 0.01).
      EX completed all tests faster than NO (~3 s, p < 0.01). The average number of
      visual mistakes was significantly lower for EX than NO in all tests (p < 0.01).
      These results demonstrated the importance of evaluating dribbling along with
      visual stimuli in young soccer EX and NO players.

PMID- 29058472
TI  - A case control association study of ACE gene polymorphism (I/D) with hypertension
      in Punjabi population from Faisalabad, Pakistan.
AB  - Angiotensin converting enzyme (ACE) is a key component of renin angiotensin
      aldosterone system. It converts angiotensin I to angiotensin II.
      Insertion/deletion (I/D) polymorphism of ACE gene is found associated with
      several complications. However, its association with hypertension and related
      metabolic diseases is still controversial. So, the aim of the present study was
      to check this association for Punjabi population from Faisalabad, Pakistan. For
      this purpose, blood samples (patients = 100, controls = 48) were collected and
      several biochemical parameters were measured. Genotyping for ACE (I/D)
      polymorphism was performed by polymerase chain reaction (PCR) assay. ID genotype
      is found prevalent in the studied population as 41% in control subjects and 61%
      in patients. Furthermore, chi-square analysis showed significant (p = 0.005)
      difference for genotypic frequencies between both groups. One-way ANOVA for
      association of II, ID, and DD genotypes with anthropometric, clinical, and
      biochemical parameters showed that in patient group, DD genotype is significantly
      (p = 0.041) associated with systolic blood pressure (SBP). Moreover, ID genotype
      is found associated with the presence of cardiovascular diseases. This study
      concludes that DD genotype is strongly associated with higher SBP in hypertensive
      patients.

PMID- 29058471
TI  - Assessment of the validity of the CUDIT-R in a subpopulation of cannabis users.
AB  - BACKGROUND: The Cannabis Use Disorders Identification Test-Revised (CUDIT-R) is
      an 8-item measure used to screen for cannabis use disorders (CUD). Despite
      widespread use of the tool, assessments of the CUDIT-R's validity in
      subpopulations are limited. OBJECTIVES: The current study tested the structural
      validity and internal consistency of one of the most widely used screening
      measures for CUD (i.e., CUDIT-R) among a sample of military veterans who use
      cannabis for medicinal purposes. METHODS: The present study used confirmatory
      factor analysis (CFA) to test the internal consistency and validity of the single
      factor structure of the original screener among a sample of veterans who use
      cannabis for medicinal purposes (n = 90 [90% male]; Mage = 55.31, SD = 15.37).
      Measures included demographics and the CUDIT-R, obtained from the baseline
      assessment of an ongoing longitudinal study. RESULTS: The CFA revealed that the
      single-factor model previously validated in recreational using samples only
      accounted for 38.34% of total variance in responses on the CUDIT-R (chi2 = 66.09,
      df = 28, p < 0.05; RMSEA = 0.06) and demonstrated acceptable but modest internal
      consistency (Cronbach's alpha = 0.73). CONCLUSION: More psychometric work is
      needed to determine the reliability and validity of using the CUDIT-R to screen
      for CUD among military veterans who use medicinal cannabis and other
      subpopulations of cannabis users.

PMID- 29058473
TI  - Structural Validation and Multiple Group Assessment of the Short Internalized
      Homonegativity Scale in Homosexual and Bisexual Men in 38 European Countries:
      Results From the European MSM Internet Survey.
AB  - Internalized homonegativity (IH) is the internalization of negative attitudes and
      assumptions about homosexual people by homosexual people themselves. To measure
      IH, Smolenski, Diamond, Ross, and Rosser (2010) and Ross, Rosser, and Smolenski
      (2010) revised the Reactions to Homosexuality Scale (RHS) to develop the Short
      Internalized Homonegativity Scale (SIHS) with eight items. Using the European Men
      Who Have Sex With Men Internet Survey (EMIS) data, with an analytic sample of
      130,718 gay and bisexual men in 38 European countries, we confirmed the validity
      of the SIHS scale in both training and validation data, in strata of Ross, Berg,
      et al.'s (2013) three "homosexual discrimination" country clusters, of age, and
      of education level. However, the performance was less adequate in comparison of
      gay versus bisexually identified individuals. The latent SIHS structure contains
      only minor variations across these three strata. The seven-item scale performed
      as well as the eight-item scale. The SIHS is a promising candidate for standard
      IH measures, which is invariant across cultural, age, and educational strata.

PMID- 29058474
TI  - Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from
      Human Gingiva-Derived Mesenchymal Stem Cells.
AB  - Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues
      received considerable interest in regenerative medicine, particularly in nerve
      regeneration owing to their embryonic origin and ease of harvest. Proliferation
      efficacy and differentiation capacity into diverse cell lineages propose dental
      MSCs as an in vitro tool for disease modeling. In this study, we investigated the
      spontaneous differentiation efficiency of dental MSCs obtained from human gingiva
      tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage
      41, the morphology of hGMSCs changed from typical fibroblast-like shape into
      sphere-shaped cells with extending processes. Next-generation transcriptomics
      sequencing showed increased expression of neural progenitor markers such as NES,
      MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such
      as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41.
      Immunocytochemistry results showed suppression of neurogenesis repressors TP53
      and p21, whereas Western blot results revealed the expression of neurotrophic
      factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy
      of hGMSCs to differentiate into neural precursor cells over prolonged passages
      and that these cells may assist in producing novel in vitro disease models that
      are associated with neural development.

PMID- 29058475
TI  - Needing to Belong: First Practice Placement Experiences of Children's Nursing
      Students.
AB  - This study examines first year children's nursing students' anxieties before
      their first practice placement and their support needs during that time.
      Strategies to address needs are highlighted. A questionnaire was completed by
      children's nursing students (n = 21) before their initial practice placement to
      establish their expectations and concerns. A subgroup (n = 5) took part in a
      focus group following placement to establish consensus around the support that
      helped and what could help future students prepare for first placement. The
      resultant data indicated the importance of students having a sense of belonging
      to their practice placement, trusting website information, induction days, and
      the involvement of a more senior student in their preparation, in addition to
      facilitative mentors. Using similar methodology to that used with students, a
      subgroup of professional staff took part in two focus groups (FG1 n = 5, FG2 n =
      4) to establish consensus around support initiatives using areas identified by
      students as priorities that could better facilitate this initial practice
      placement. Although commonalities existed within both students and professionals,
      some differences were highlighted. A student's first practice placement is of
      utmost importance in affirming their choice to study nursing. Academic and
      clinical staff play a crucial part in this decision-making.

PMID- 29058476
TI  - Iridoid glycosides and polyphenolic compounds from Teucrium chamaedrys L.
AB  - In this work, the phytochemical analysis of Teucrium chamaedrys L. collected in
      Italy was reported. Eight compounds were isolated and identified by means of
      classical column chromatography and spectroscopic techniques, such as NMR and MS.
      In detail, these compounds were: verbascoside (1), forsythoside b (2), samioside
      (3), alyssonoside (4), harpagide (5), 8-O-acetyl-harpagide (6), cirsiliol (7) and
      beta-arbutin (8). The presence of these compounds, in particular iridoids and
      phenyl-ethanoid glycosides, has a chemotaxonomic relevance and results to be in
      perfect accordance with the current botanical classification of the species. In
      addition, it provides a phytochemical rationale for the use of this particular
      plant in the ethno-pharmacological field. Conversely, it is worth of mention the
      absence of potentially toxic components, unlike to what observed in other species
      of the genus which can no longer be used for ethno-medicinal purposes.

PMID- 29058478
TI  - Improving the quality of discrete-choice experiments in health: how can we assess
      validity and reliability?
AB  - INTRODUCTION: The recent endorsement of discrete-choice experiments (DCEs) and
      other stated-preference methods by regulatory and health technology assessment
      (HTA) agencies has placed a greater focus on demonstrating the validity and
      reliability of preference results. Areas covered: We present a practical overview
      of tests of validity and reliability that have been applied in the health DCE
      literature and explore other study qualities of DCEs. From the published
      literature, we identify a variety of methods to assess the validity and
      reliability of DCEs. We conceptualize these methods to create a conceptual model
      with four domains: measurement validity, measurement reliability, choice
      validity, and choice reliability. Each domain consists of three categories that
      can be assessed using one to four procedures (for a total of 24 tests). We
      present how these tests have been applied in the literature and direct readers to
      applications of these tests in the health DCE literature. Based on a stakeholder
      engagement exercise, we consider the importance of study characteristics beyond
      traditional concepts of validity and reliability. Expert commentary: We discuss
      study design considerations to assess the validity and reliability of a DCE,
      consider limitations to the current application of tests, and discuss future work
      to consider the quality of DCEs in healthcare.

PMID- 29058477
TI  - An Effective Intervention for Diabetic Lipohypertrophy: Results of a Randomized,
      Controlled, Prospective Multicenter Study in France.
AB  - BACKGROUND: Lipohypertrophy (LH) is highly prevalent and is potentially harmful
      to insulin-injecting patients. METHODS: In this study, we assessed the impact of
      injection technique (IT) education, including use of a 4-mm pen needle on insulin
      treated patients with clinically observed LH in a randomized, controlled,
      prospective multicenter study in France with follow-up of 6 months. Intensive
      education and between-visit reinforcement were given to the intervention group.
      Control patients received similar messages at study outset. RESULTS: A total of
      123 patients were recruited (age 52.1 +/- 15.7 years; men 70.7%; body mass index
      >30 kg/m2: 34.2%; type 1: 53.7%; years with diabetes mellitus: 18.1 +/- 10.5), of
      which 109 patients were included in the final analysis. The intervention group (n
      = 53) showed a significant decrease of total daily dose of insulin (average at
      baseline: 54.1 IU) at 3 months (T-3) and 6 months (T-6), reaching just over 5 IU
      versus baseline (P = 0.035). Corresponding, although not significant, decreases
      occurred in controls (n = 56); between-group differences were not significant.
      There were significant decreases in HbA1c (up to 0.5%) at T-3 and T-6 in both
      groups, with no significant differences between groups. A significant number of
      intervention patients improved their IT habits; about half achieved ideal IT
      habits by T-3 versus a quarter of control patients. By T-6, 2/3 of intervention
      patients achieved either ideal or acceptable IT habits, while only 1/3 of control
      patients did. CONCLUSIONS: Our intervention was effective in both study arms,
      however, to a greater degree and more rapidly in the intervention group.
      Widespread application of this intervention could be highly cost-effective.

PMID- 29058479
TI  - Simultaneous Detection of Multiple Salmonella Serovars from Milk and Chicken Meat
      by Real-Time PCR Using Unique Genomic Target Regions.
AB  - A novel genomic and plasmid target-based PCR platform was developed for the
      detection of Salmonella serovars Heidelberg, Dublin, Hadar, Kentucky, and
      Enteritidis. Unique genome loci were obtained through extensive genome mining of
      protein databases and comparative genomic analysis of these serovars. Assays
      targeting Salmonella serovars Hadar, Heidelberg, Kentucky, and Dublin had 100%
      specificity and sensitivity, whereas those for Salmonella Enteritidis had 97%
      specificity and 88% sensitivity. The limits of detection for Salmonella serovars
      Heidelberg, Kentucky, Hadar, Enteritidis, and Dublin were 12, 9, 40, 13, and
      5,280 CFU, respectively. A sensitivity assay was also performed by using milk
      artificially inoculated with pooled Salmonella serovars, yielding a detection
      limit of 1 to10 CFU/25 mL of milk samples after enrichment. The minimum DNA
      detected using the multiplexed TaqMan assay was 75.8 fg (1.53 * 101 genomic
      equivalents [GE]) for Salmonella Heidelberg, 140.8 fg (2.8 * 101 GE) for
      Salmonella Enteritidis, and 3.48 pg (6.96 * 102 GE) for Salmonella Dublin. PCR
      efficiencies were 89.8% for Salmonella Heidelberg, 94.5% for Salmonella
      Enteritidis, and 75.5% for Salmonella Dublin. Four types of 30 pasteurized milk
      samples were tested negative by culture techniques and with a genus-specific
      Salmonella invA gene PCR assay. Among 30 chicken samples similarly tested, 12
      (40%) were positive by both culture and the invA PCR. Testing of these 12 samples
      with the serovar-specific PCR assay detected single and mixed contamination with
      Salmonella Kentucky, Salmonella Enteritidis, and Salmonella Heidelberg. Five
      unique primers were designed and tested by multiplex conventional PCR in
      conjunction with the use of the multiplex TaqMan assay with three of the primers.
      The diagnostic assays developed in this study could be used as tools for routine
      detection of these five Salmonella serovars and for epidemiological
      investigations of foodborne disease outbreaks.

PMID- 29058480
TI  - Clinical and demographic predictors of concussion resolution in adolescents: A
      retrospective study.
AB  - Concussions in adolescents are a growing public health concern. The aim of this
      study was to identify clinical (e.g., concussion history, migraine history,
      learning disabilities/ADHD) and demographic factors (e.g., age, sex, race, health
      insurance status, mechanism of injury, education) that predict concussion
      recovery times. In a retrospective cohort study of 118 adolescents 13-19 years
      old who were evaluated for an acute concussion (<=10 days from injury), recovery
      times were calculated from the date of concussive injury to the date of clearance
      to return to play and/or normal activities. The median time to recovery was 17
      days. Predictors of longer recovery included ADHD (HR = .221, 95% CI = .095 -
      .514, p < .001) and prior concussion (HR = .564, 95% CI = .332 - .959, p = .03).
      Student athletic insurance and public insurance were predictors of shorter
      recovery times (HR = 3.98, 95% CI = 1.25 - 12.65, p = .02 and HR = 3.33, 95% CI =
      1.09 - 10.15, p = .03, respectively). In adolescents with prior concussion or
      ADHD, clearance to return to play/ normal activities may be delayed. Further
      research is needed to validate the impact of SES/health insurance on concussion
      recovery time.

PMID- 29058481
TI  - Effects of antiretroviral treatment and nadir CD4 count in progression to
      cardiovascular events and related comorbidities in a HIV Brazilian cohort: a
      multi-stage approach.
AB  - The use of highly active antiretroviral therapy has resulted in changes of
      comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS
      related events. The occurrence of cardiovascular events is greater in PLHIV, but
      the mechanism responsible for it is still controversial. This article aimed to
      investigate factors associated with the progression to cardiovascular events in
      PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio
      de Janeiro-Brazil. Clinical progression was stratified in five states: No
      comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3),
      hypertension and lipid abnormalities (s4) and major cardiovascular events
      (stroke, coronary artery disease, thrombosis or death) (s5). Semi-Markov models
      evaluated the effects of cardiovascular traditional factors, treatment and
      clinical covariates on transitions between these states. Hazard Ratios (HR) and
      95% confidence intervals (CI) were provided. In addition to traditional factors
      (age, sex, educational level and skin color), the development of one comorbidity
      (lipid abnormalities or hypertension) increased in patients with low nadir CD4
      (<50 cells/mm3), (HR = 1.59, CI 1.11-2.28 and 1.36, CI 1.11-1.66, respectively).
      The risk to experience a second comorbidity (s3->s4) increased 75% with low nadir
      CD4. Age was the only factor that increased the risk of major cardiovascular
      events once having lipid abnormalities with or without hypertension (s3,s4->s5).
      The prolonged use of certain antiretroviral drugs (abacavir, didanosine,
      ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct
      transition (s1->s5) to major cardiovascular events (HR = 5.29, CI 1.16-24.05).
      This analysis suggests that prolonged use of certain antiretroviral drugs led
      directly to major cardiovascular events, while low nadir CD4 only affected the
      occurrence of lipid abnormalities and hypertension. Management strategies,
      including rational use of complex exams (such as, computed-tomography
      angiography), statins and antihypertensives, should be developed based on the
      distinct roles of antiretroviral use and of HIV infection itself on the
      progression to cardiovascular events.

PMID- 29058482
TI  - Identification and determination of naturally occurring folates in grains of rice
      (Oryza sativa L.) by UPLC-MS/MS analysis.
AB  - The genetic potential and biofortification of India-grown rice with bioavailable
      folate has not been studied yet. The objectives of this study were to determine
      the folates concentration in four cultivars of rice through UPLC-MS/MS. Total
      folate concentration in rice cultivars ranged from 11.0 to 51 MUg/100 g with a
      mean of 26.0 MUg/100 g. Among the four rice cultivars, the pigmented grain
      cultivar Nootripathu possesses two-fold rich sources of total folates than the
      other three non-pigmented grain cultivars. The average value of 100 g serving of
      rice grains could provide the amount of recommended daily allowance (% RDA) of
      dietary folates (6.5%) for adults, which ranged from 2.7-12.7%. Among the 5
      individual forms of folates, 5-methyltetrahydrofolate was most abundant in rice
      cultivars followed by 10-Formylfolic acid and folic acid. The result of this
      study has been useful for biofortification of folates in rice.

PMID- 29058483
TI  - Fear-Mongering or Fact-Driven? Illuminating the Interplay of Objective Risk and
      Emotion-Evoking Form in the Response to Epidemic News.
AB  - This study examined the veracity of the common assumption that news coverage of
      epidemic outbreaks spawns heightened fears and risk perceptions. An online
      experiment with 1,324 participants investigated the interplay of the form of news
      coverage (factual/emotion-laden) and key aspects of actual risk (low/high
      vulnerability, low/high severity) on audience responses. Participants read one of
      eight versions of a newspaper article followed by measures on risk perceptions,
      negative affect, behavioral intentions, and perceived sensationalism. Risk
      perceptions and fear were primarily driven by objective risk characteristics,
      whereas emotion-laden news form only increased perceptions of disease severity,
      not of fear or personal vulnerability.

PMID- 29058484
TI  - Neurite Outgrowth Inhibitor B Receptor: A Versatile Receptor with Multiple
      Functions and Actions.
AB  - Members of the reticulon protein family are predominantly distributed within the
      endoplasmic reticulum. The neurite outgrowth inhibitor (Nogo) has three subtypes,
      including Nogo-A (200 kDa), Nogo-B (55 kDa), and Nogo-C (25 kDa). Nogo-A and Nogo
      C are potent Nogos that are predominantly expressed in the central nervous
      system. Nogo-B, the splice variant of reticulon-4, is expressed widely in
      multiple human organ systems, including the liver, lung, kidney, blood vessels,
      and inflammatory cells. Moreover, the Nogo-B receptor (NgBR) can interact with
      Nogo-B and can independently affect nervous system regeneration, the chemotaxis
      of endothelial cells, proliferation, and apoptosis. In recent years, it has been
      demonstrated that NgBR plays an important role in human pathophysiological
      processes, including lipid metabolism, angiogenesis, N-glycosylation, cell
      apoptosis, chemoresistance in human hepatocellular carcinoma, and epithelial
      mesenchymal transition. The pathophysiologic effects of NgBR have garnered
      increased attention, and the detection and enhancement of NgBR expression may be
      a novel approach to monitor the development and to improve the prognosis of
      relevant human clinical diseases.

PMID- 29058485
TI  - Accuracy analysis of line-based registration for image guided neurosurgery at
      different operating areas - a phantom study.
AB  - Space registration is the primary function of neuronavigation systems. According
      to the stage of the operation, the registration could be classified as rigid and
      non-rigid methods. Scientists have proposed three types of rigid registration
      methods: point-based registration (PBR), line-based registration (LBR), and
      surface-based registration (SBR). PBR has been widely used in clinical
      applications. Recently, LBR was proposed as a new spacing registration method.
      However, the range and accuracy of LBR are still not defined for clinical
      applications. In this paper, LBR has been evaluated directly with target
      registration error (TRE) in different operating areas: sphenoid-frontal, parietal
      temporal, and occipital areas. We used two head phantoms: elastic and rigid
      phantoms. After scanning with computerized tomography (CT), the difference
      between the TRE of the elastic and rigid phantom had been evaluated based on LBR
      method. Then, LBR had been employed at the rigid phantom using different line
      patterns: single (100 points), double (200 points), triple (300 points), and
      quartic lines (400 points). TRE were directly measured on the phantom. Then, t
      tests were applied to evaluate the difference between the TRE of LBR of both the
      phantoms and line patterns. Results indicate that there is no statistical
      difference in TRE between the phantoms. TRE were reduced to less than 3 mm after
      the use of double lines which was significantly less than those after the use of
      single lines. Except for sphenoid tumor, the other operating areas showed
      statistical differences in TRE between double and triple lines. Except for
      temporal tumor, the differences between the TRE of triple and quartic lines are
      not significant.

PMID- 29058486
TI  - High-quality mesh generation for human hip based on ideal element size: methods
      and evaluation.
AB  - The objective of this work was to obtain high-quality mesh generation results for
      the human hip. This study adopted an edge-collapse algorithm based on quadric
      error metrics to simplify the hip model. The adjacent triangular areas and a cost
      function that considered the mean value of error were introduced to avoid error
      accumulation and ensure invariant geometric features. Local mesh refinement was
      achieved by constructing a comprehensive size field. Finally, high-quality
      surface and volume meshes were generated using the advancing-front technique
      (AFT) and Delaunay algorithms. Two human hipbones, 13 muscles, and one articular
      cartilage sample were modelled. The hip model was simplified and the mesh was
      generated using the method proposed in this study. The smallest angle of most
      surface mesh elements was greater than 45 degrees , and the triangular numbers in
      this optimal angle interval were superior to those generated by the AFT
      algorithms. Eight quality evaluation parameters of the mesh model were tested
      using the check-elems tool. The femoral meshing results in this work were more
      accurate than those obtained with the AFT algorithms. The results of the vastus
      lateralis mesh generation were superior to the results obtained with the existing
      algorithm, except for the volume skew parameter. The proportions for the high
      quality tetrahedral elements obtained using Wang's algorithm for the femur and
      the vastuslateralis muscle were 17.81% and 24.50%, respectively. The proportions
      obtained using the hypermesh software were 16.31% and 22.87% for the femoral and
      vastuslateralis models, respectively. The proposed method had better adaptability
      to the complex model. The generated mesh was uniform and contained smooth
      transitions. The mesh generation result was similar to the original geometric
      model, which made the assembly model fit more accurately. This was significant
      for the convergence of the finite-element analysis program.

PMID- 29058487
TI  - LC3-Dependent Autophagy in Pig 2-Cell Cloned Embryos Could Influence the
      Degradation of Maternal mRNA and the Regulation of Epigenetic Modification.
AB  - In this study, the distribution as well as the effect of autophagy on
      reprogramming in pig cloned embryos were observed immediately after somatic cell
      nuclear transfer. Results showed that the LC3 was at the highest level in cloned
      embryos at 2-cell stage, and it decreased with the development from 2-cell stage
      to blastocyst. Different to cloned embryos, the intensity of LC3 in
      parthenogenetic activation (PA) embryos was at the highest level at 4-cell stage.
      A markedly higher level of Bmp15, H1foo, and Dppa3 was shown in cloned embryos at
      2-cell stage (p < 0.05 or p < 0.01), but a significantly lower level of LC3,
      Sox2, and eIF1A was observed at 4-cell stage (p < 0.05), compared with PA
      embryos. When the efficient interfering by the LC3 siRNA was performed on the
      cloned embryos (p < 0.01), not only the mRNA level of maternal Cyclin B, Bmp15,
      Gdf9, c-mos, H1foo, and Dppa3 was increased significantly (p < 0.05), but also
      the expression of Dnmt1 and Dnmt3b was obviously upregulated (p < 0.05). Although
      the expression of Sox2 and Oct4 is not changed, the expression of Stat3 decreased
      significantly (p < 0.05). Furthermore with the treatment of 200 nM rapamycin, the
      expression of eIF1A and Stat3 was significantly increased at 4-cell stage. In
      conclusion, the LC3-dependent autophagy mainly occurred in cloned embryos at 2
      cell stage, but at 4-cell stage in PA embryos. In addition, the modulation of
      autophagy could affect genome activation by influencing the degradation of
      maternal mRNA and regulating the expression of DNA methyltransferase.

PMID- 29058488
TI  - Evaluation of different metrics as an index for the assessment of arterial
      stiffness.
AB  - Elevated intravascular pressure is a contributing factor to increased arterial
      stiffness, and is a risk factor for cardiovascular morbidity and mortality.
      Assessment of arterial stiffness is of importance in evaluating cardiovascular
      risk. Pulse wave velocity (PWV) has been broadly used in the assessment of
      arterial stiffness. We compared three different metrics of arterial stiffness to
      PWV. Hemodynamic recordings were carried out in anesthetized hypertensive and
      normotensive rats (n = 25; 13-14 weeks old). Four parameters were calculated
      (PWV, elastic modulus (Einc), stiffness index (beta), and pressure-strain modulus
      (Ep)) as metrics of arterial stiffness. Hypertensive in comparison to
      normotensive rats had significantly higher systolic and diastolic blood
      pressures. Metric for arterial stiffness were significantly (p < 0.002) higher in
      hypertensive animals: PWV (8.46 +/- 2.01 vs. 6.39 +/- 1.28 m/s), Ep (0.246 +/-
      0.019 vs. 0.137 +/- 0.010 dyn/cm2 * 10-6), Einc (17.5 +/- 1.8 vs. 10.1 +/- 0.9
      dyn/cm2 * 10-6), and beta (2.43 +/- 0.11 vs. 1.98 +/- 0.08) (mean+/-SE). Bland
      Altman analysis revealed beta as the only metric aligned with PWV in hypertensive
      state. We find in state of reduced arterial compliance associated with high
      systemic pressure, beta but not Einc or Ep is an index of arterial stiffness
      showing agreement with PWV.

PMID- 29058489
TI  - Genome-wide association study for white coat effect in Japanese middle-aged to
      elderly people: The HOMED-BP study.
AB  - BACKGROUND: White coat effect (WCE), the blood pressure (BP) difference between
      clinical and non-clinical settings, can lead to clinical problems such as
      misdiagnosis of hypertension. Etiology of WCE has been still unclear, especially
      from genetic aspects. The present article investigated association between genome
      wide single nucleotide polymorphisms (SNPs) and WCE in patients with essential
      hypertension. METHODS: The present cross-sectional analyses were based on 295
      Japanese essential hypertensive outpatients aged ?40 years enrolled in randomized
      control study, Hypertension Objective Treatment Based on Measurement by
      Electrical Devices of Blood Pressure (HOMED-BP) study, who were not taking
      antihypertensive medications before the randomization. Home and clinic BP were
      measured. WCE was defined by subtracting home BP from clinic BP. Genotyping was
      conducted with 500K DNA microarray chips. Association between genome-wide SNPs
      and WCE were analyzed. For replication (p < 10-4), we analyzed participants from
      Ohasama study who took no antihypertension medications and whose SNPs were
      collected. RESULTS: Genome-wide SNPs were not significantly associated with WCE
      of systolic and diastolic BP after corrections of multiple comparisons (p < 2 *
      10-7). We found suggestive SNPs associated with WCE of systolic and diastolic BP
      (p < 10-4). However, the consistent results were not obtained in the replication
      study. CONCLUSION: The present article showed no significant association between
      genome-wide SNPs and WCE. Since there were several suggestive SNPs associated
      with WCE, the present study warrants a further study with bigger sample size for
      investigating the genetic influence on WCE.

PMID- 29058491
TI  - A Review of Primary Thyroid Lymphoma: Molecular Factors, Diagnosis and
      Management.
AB  - : Purpose/aim: To focus on current aspects of primary thyroid lymphoma (PTL),
      which is a rare clinical entity usually manifested by a rapidly growing mass in
      the neck that can cause pressure symptoms. MATERIALS AND METHODS: Relevant papers
      in PubMed published through June 2017 were selected to track updated information
      about PTL with an emphasis on diagnosis and novel therapeutic management.
      RESULTS: The most frequent cases include non-Hodgkin lymphoma derived from B
      cells, mainly diffuse large B-cell lymphoma (DLBCL) followed by mucosa-associated
      lymphoid tissue (MALT) lymphoma or a mixed type. Other subtypes are less common.
      Lymphomas derived from T-cells and Hodgkin lymphomas are extremely rare.
      Hashimoto's autoimmune thyroiditis has been implicated as a risk factor for
      lymphoma. At the molecular level, the Wnt5a protein and its receptor Ror2 are
      involved in the course of the disease. Ultrasonography, fine needle aspiration
      (FNA) biopsy, and core or open biopsy combined with new diagnostic facilities
      contribute to an accurate diagnosis. An increased potential exists for a cure
      without the need for a radical surgical procedure. Modern chemoradiation therapy
      plus the monoclonal antibody rituximab, which acts against CD20, have limited the
      need for surgical interventions and provide an excellent outcome in most cases.
      However, some cases have resulted in treatment failure or recurrence.
      CONCLUSIONS: A multidisciplinary approach must be used to define the management
      policy in each case. Future efforts by researchers are likely to be focused on
      the molecular level.

PMID- 29058490
TI  - Incidence, diagnostic, treatment and outcome of patients diagnosed with cancer of
      the pancreas during 1986-2009: a population-based study.
AB  - OBJECTIVE: Limited data exist on the changes in the epidemiology of pancreatic
      cancer and outcomes over the last decades in population-based cohorts. We aimed
      to compare the incidence of pancreatic cancer, diagnostic, treatment and survival
      among patients diagnosed over the period 1986-2009. MATERIALS AND METHODS: A
      retrospective, nationwide, population-based study. All patients diagnosed with
      pancreatic cancer in Iceland in two periods, 1986-1997 (P1) and 1998-2009 (P2)
      were identified through the Icelandic Cancer Registry and relevant clinical
      information obtained from medical records. RESULTS: A total of 645 patients were
      identified, 296 in P1 and 349 in P2 (NS). The incidence during P1 was 6.8 per
      100,000 inhabitants and 6.2 during P2 (NS). Among biopsy-proven cancers,
      adenocarcinoma was diagnosed in 89% of the cases in P1 and in P2 in 93% of the
      cases. Overall 38 (14%) in P1 underwent resection and 22 (7%) in P2 (p < .0004).
      Patients diagnosed in P2 had longer survival at 6 months (p = .015, log-rank
      test) and one year (p = .0206) after diagnosis. A total of 4/296 (1.4%) in P1
      survived more than 5 years and 3/349 (0.9%) in P2 (NS). CONCLUSIONS: The
      incidence among patients with pancreatic cancer in Iceland did not show major
      changes during the last 20 years. Diagnostic approach has changed considerably
      demonstrating more patients that are not 'resectable'. Survival rate at 6 months
      and one year has improved over the last two decades whereas the 5-year prognosis
      has not improved.

PMID- 29058492
TI  - Association between the soluble epoxide hydrolase gene and preeclampsia.
AB  - OBJECTIVE: In this study the association between K55R polymorphism, methylation
      level of the EPHX2 promoter region, and PE was investigated in 520 individuals
      including 260 PE patients and 260 healthy pregnant women. METHODS: K55R
      polymorphism and methylation level of the EPHX2 promoter were determined by the
      real-time PCR using double-dye hydrolysis probes and methylation-sensitive high
      resolution melting analysis, respectively. RESULTS: The presence of the K55R
      polymorphism was significantly higher in cases (28.1%) than controls (17.3%), and
      was associated with increased risk of PE (OR: 1.86; 95% CI: 1.09-2.63).
      Methylation levels of the EPHX2 promoter region in cases were significantly lower
      than controls. A 2.83 times increased PE risk was observed in pregnant women with
      EPHX2 promoter methylation levels of <25% (OR: 2.83; 95% CI: 1.15-6.91).
      CONCLUSION: In conclusion, hypomethylation of the promoter region of EPHX2 and
      K55R polymorphism were associated with significant increased risk of PE. sEH
      enzyme may play a role in the pathogenesis of PE by contributing to reduction of
      the vasodilatator, anti-hypertensive, and anti-inflammatory effects of EETs by
      rapid degradation of these molecules.

PMID- 29058493
TI  - Induction of labour: clinical predictive factors for success and failure.
AB  - Induction of labour (IOL) is a widely-used practice in obstetrics. Our aim was to
      evaluate predictors of vaginal delivery in postdate pregnancies induced with
      prostaglandins. We conducted a retrospective cross-sectional study with analytic
      component. A total of 145 women, admitted for IOL after the 41st week of
      gestation, were induced with a vaginal pessary releasing prostaglandins. Type of
      delivery, whether vaginal or caesarean, was the outcome. Several maternal and
      foetal variables were investigated. The Kaplan-Maier curves, monovariate and a
      multivariate logistic regression were carried out. In our population, 80.7% of
      women had vaginal delivery after the induction. Multiparity and a high Bishop
      score at the beginning of the IOL were protective factors for a vaginal delivery
      (respectively OR 0.16, p = .028 and OR 0.62, p = .034) while age >35 years, and
      the foetal birth weight >3500 g at the birth, resulted in being risk factors for
      caesarean section (respectively OR 4.20, p = .006 and OR 3.63, p = .013). IMPACT
      STATEMENT What is already known on this subject: Induction of labour (IOL) is a
      widely used practice in obstetrics. Scientific literature shows several
      predictors of successful induction, although there is no unanimity except for
      'multiparity' and 'favourable Bishop score' which are associated with positive
      outcome of the induction. The main difficulty in finding other predictive factors
      is the heterogeneity of this field (different local protocols in each hospital,
      type of induction, populations and outcomes chosen in each study). In addition to
      that, populations are not always comparable due to the different gestation. For
      this reason, we decided to select a specific population of women, such as low
      risk postterm pregnancies induced with prostaglandins, in order to detect
      possible predictive factors for the success of the IOL for women with
      uncomplicated pregnancies. What the results of this study add: Our study agrees
      with existing literature that 'multiparity' and 'Bishop score' are linked with
      the success of IOL and adds that 'maternal age' and 'foetal birth weight' are
      significant risk factors for the population of uncomplicated post term
      pregnancies induced with prostaglandins. What the implications are of these
      findings for clinical practice and/or further research: Our results agreed with
      the existing literature regarding parity and Bishop score but not for maternal
      age and birth weight. This adds new precious data to the literature which could
      be used for systematic reviews and for implementing IOL guidelines and protocols,
      nationally and internationally. Our findings could be also used for guiding
      future research in this field. It will be interesting to investigate the
      existence of not just specific factors but also any combination of variables
      which could predict the success of the procedure. At the moment these information
      cannot be used in terms of decision making for healthcare professionals as no
      variable is 100% predictive but once further research will be added, we may be
      able to know when is best time to start the IOL, how to facilitate the success of
      the procedure and how to best support the woman throughout the whole experience.

PMID- 29058494
TI  - Sentinel Lymph Node Status is a Main Prognostic Parameter Needful for the Correct
      Staging of Patients with Melanoma Thicker than 4 mm: Single-Institution
      Experience and Literature Meta-Analysis.
AB  - PURPOSE OF THE STUDY: The usefulness of sentinel lymph node biopsy in thick
      melanomas is debated. The aim of this study was to evaluate the possible
      prognostic significance of sentinel lymph node biopsy in T4 melanoma patients and
      to verify whether this was a homogeneous group of patients with similar poor
      behavior. MATERIALS AND METHODS: A retrospective observational study was
      performed. Data were extracted from the Tuscan Regional Referral Center database.
      The outcome of sentinel lymph node-negative and sentinel lymph node-positive T4
      melanomas were compared. A systematic review of published series on this issue
      and a meta-analysis were performed. RESULTS: Among 125 T4 melanoma patients, 53
      patients (42.4%) were sentinel lymph node-positive and 72 (57.6%) patients were
      sentinel lymph node-negative. The 5-year and the 10-year melanoma specific
      survival were 81.9% and 72.3% for sentinel lymph node-negative patients and 42.4%
      and 17.9% (P < 0.001) for sentinel lymph node-positive patients. A positive
      sentinel lymph node showed an HR of 3.08. The meta-analysis confirmed that there
      was a significantly greater risk of death for patients with thick melanoma and
      positive sentinel lymph node (RR 1.75). CONCLUSIONS: The results of the study
      point out that the sentinel lymph node biopsy is required for the correct staging
      of patients with melanoma thicker than 4 mm and that the status of sentinel lymph
      node is a significant predictor of melanoma specific survival. This knowledge
      allows early surgical and adjuvant treatment as well as appropriate trial
      enrollment and tailored follow-up.

PMID- 29058495
TI  - New workflows for clinical video recordings in cleft care.
AB  - The Cleft team at Cambridge University Hospitals (CUH), Cleft.NET.East (CNE),
      were experiencing many technical issues with their video recording systems and
      processes, resulting in poor record keeping and audit performance. It became
      apparent that the equipment needed to be updated and replaced, with new workflows
      implemented to improve the quality and consistency in patients' records.
      Following a review carried out with the Cleft team, equipment was identified and
      workflows were implemented which improved the processes already in place. These
      changes have resulted in improved quality of records, better audit performance;
      time saved for key clinicians, more efficient running of clinics and improved
      patient experience.

PMID- 29058496
TI  - A protocol for interagency collaboration and family participation: Practitioners'
      perspectives on the Client Network Consultation.
AB  - Interagency collaboration has many advantages, but seems hard to realise in
      practice. In Belgium, the need for collaboration between the practitioners in the
      field of child welfare and child psychiatry, especially for children and
      adolescents with complex health care needs, was identified. Children with complex
      health care needs require coordinated care and collaboration between the
      different sectors in child mental health care (child welfare, child psychiatry,
      disability care). The authors have developed a standardised protocol based on the
      wraparound principles, which support interagency collaboration with family
      participation, named Client Network Consultation (CNC). Focus groups evaluated
      the CNC by eliciting practitioners' views on the structure, content and impact of
      collaborative interagency protocols with family involvement. Thematic analysis
      revealed four core themes: (1) Empowering the child and the family; (2) Utilising
      the strength of the collective; (3) Being considerate versus constructive a
      dilemma for participants in CNC; and (4) The structure of a protocol offers
      opportunities and challenges. Results of the study offer implications for daily
      practice. Several challenges for interprofessional (IP) practice in the complex
      field of child and adolescent mental health care are described. The value of the
      CNC protocol to engage families in a clinical process is also discussed.

PMID- 29058497
TI  - The occurrence of early impaired self-awareness after traumatic brain injury and
      its relationship with emotional distress and psychosocial functioning.
AB  - OBJECTIVE: To describe the occurrence of impaired self-awareness (ISA) after
      traumatic brain injury (TBI) and its association with emotional distress and
      psychosocial functioning following discharge. DESIGN: Prospective cohort design
      with data collection at discharge and 1-, 3- and 6-month follow-up. PARTICIPANTS:
      81 adults with TBI. MEASURES: Self-awareness was measured using a discrepancy
      score generated from the Mayo-Portland Adaptability Index (MPAI-4) Ability
      subscale, and significant other's ratings of Item 20 on the MPAI-4. Other
      measures were the Depression Anxiety Stress Scale-21 and Sydney Psychosocial and
      Reintegration Scale. RESULTS: The discrepancy score method identified more cases
      of ISA than the single-item rating by significant others. Using discrepancy
      scores, the occurrence of ISA was 69.1% at discharge, and for those remaining in
      the study 6 months later, it was 54.3%. Better self-awareness was associated with
      greater anxiety at discharge, and stress at discharge, 3 and 6 months later, and
      better psychosocial functioning at all time points. Participants with ISA had
      significantly poorer relationships at 6 months post-discharge after controlling
      for injury severity. CONCLUSION: Whilst self-awareness is associated with greater
      stress in patients with TBI, it is also associated with better outcomes,
      indicating the importance of targeting ISA in rehabilitation.

PMID- 29058498
TI  - Prospective health students' perceptions of the pharmacist role in the
      interprofessional team.
AB  - Negative perceptions or underdeveloped understanding of healthcare team member
      roles can impact the functionality of the team and stunt innovations in
      interprofessional practice and education. Therefore, the intent of this study was
      to explore the perception of pharmacists' role on the healthcare team by future
      team members: prospective health professional students. The study utilised a
      survey to examine these perceptions in prospective health professional students
      (n = 34) nearing the application process to health professional school. A coding
      process was used to explore open-ended text responses through a line-by-line
      analysis and identify emerging themes regarding perception of pharmacists' roles,
      responsibilities, and practice settings. Quantitative data examined perception of
      pharmacists by intended prospective profession, healthcare experience, and
      pharmacy experience. Results indicate that while prospective health professional
      students find pharmacists to be an important part of the healthcare team, they
      lack a developed understanding of pharmacists' roles, responsibilities, and
      practice settings. Identifying and addressing prospective health professional
      students' misperceptions surrounding pharmacists' roles and responsibilities may
      encourage them to make informed career decisions and shape them into more
      knowledgeable future professionals with the ability to better impact patient care
      on interprofessional teams.

PMID- 29058500
TI  - Recall of Fertility Discussion by Adolescent Female Cancer Patients: A Survey
      Based Pilot Study.
AB  - Many adolescent female cancer patients will survive into their reproductive
      years. Pediatric oncologists are advised to discuss oncofertility during
      treatment planning. In this pilot study, 19 adolescent females completed a
      retrospective survey assessing recall of a fertility discussion, satisfaction
      with fertility knowledge, and multiple factors that may influence recall,
      including parental involvement in decision-making. Eleven respondents (58%)
      remembered a discussion about infertility risk and 9 (47%) about fertility
      preservation. Most who recalled a discussion were satisfied with their fertility
      knowledge (10/11, 90.9%). In this study, we validated the feasibility of survey
      administration and identified trends in oncofertility counseling at our center.

PMID- 29058499
TI  - Direct fluorescent labeling for efficient biological assessment of inhalable
      particles.
AB  - Labeling of aerosol particles with a radioactive, magnetic, or optical tracer has
      been employed to confirm particle localization in cell compartments, which has
      provided useful evidence for correlating toxic effects of inhaled particles.
      However, labeling requires several physicochemical steps to identify
      functionalities of the inner or outer surfaces of particles, and moreover, these
      steps can cause changes in size, surface charge, and bioactivity of the
      particles, resulting in misinterpretations regarding their toxic effects. This
      study addresses this challenging issue with a goal of introducing an efficient
      strategy for constantly supplying labeled aerosol particles in a single-pass
      configuration without any pre- or post-physicochemical batch treatments of
      aerosol particles. Carbon black (CB, simulating combustion-generated soot) or
      calcium carbonate (CC, simulating brake-wear fragments) particles were constantly
      produced via spark ablation or bubble bursting, respectively. These minute
      particles were incorporated with fluorescein isothiocyanate-poly(ethylene glycol)
      2-aminoethyl ether acetic acid solution at the orifice of a collison atomizer to
      fabricate hybrid droplets. The droplets successively entered a diffusion dryer
      containing 254-nm UV irradiation; therefore, the droplets were dynamically
      stiffened by UV to form fluorescent probes on particles during solvent extraction
      in the dryer. Particle size distributions, morphologies, and surface charges
      before and after labeling were measured to confirm fluorescence labeling without
      significant changes in the properties. In vitro assays, including confocal
      imaging, were conducted to confirm the feasibility of the labeling approach
      without inducing significant differences in bioactivity compared with untreated
      CB or CC particles.

PMID- 29058501
TI  - Review of IL-17 inhibitors for psoriasis.
AB  - BACKGROUND: The development of biologic agents directed against distinct
      cytokines and receptors has advanced the therapeutic options available for
      psoriasis patients. Evidence from preclinical studies suggests that IL-17 may
      contribute to the pathogenesis of psoriasis. OBJECTIVE: The objective was to
      review the safety and efficacy profile for each IL-17 inhibitor by evaluating
      phase III clinical trial data. METHODS: We reviewed the results of phase III
      clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab.
      RESULTS: At week 12, the proportion of patients reaching Psoriasis Area and
      Severity Index (PASI 75) was above 60% for the most efficacious dose of each
      agent with favorable and comparable safety profiles. The most commonly reported
      adverse events were nasopharyngitis, headache, and upper respiratory tract
      infection. CONCLUSIONS: The clinical improvement among psoriasis patients on IL
      17 inhibitors is similar or superior to the improvement seen with commercially
      produced biologic agents available accompanied by a favorable short-term safety
      profile. The results of the phase III trials indicate that IL-17 inhibitors are
      effective therapeutic options for psoriasis patients.

PMID- 29058502
TI  - Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL.
AB  - The development of clinically functional chimeric antigen receptor (CAR) T cell
      therapy is the culmination of multiple advances over the last three decades.
      Axicabtagene ciloleucel (formerly KTE-C19) is an anti-CD19 CAR T cell therapy in
      development for patients with refractory diffuse large B cell lymphoma (DLBCL),
      including transformed follicular lymphoma (TFL) and primary mediastinal B cell
      lymphoma (PMBCL). Axicabtagene ciloleucel is manufactured from patients' own
      peripheral blood mononuclear cells (PBMC) during which T cells are engineered to
      express a CAR that redirects them to recognize CD19-expressing cells. Clinical
      trials have demonstrated the feasibility of manufacturing axicabtagene ciloleucel
      in a centralized facility for use in multicenter clinical trials and have
      demonstrated potent antitumor activity in patients with refractory DLBCL. Main
      acute toxicities are cytokine release syndrome and neurologic events.
      Axicabtagene ciloleucel holds promise for the treatment of patients with CD19
      positive malignancies, including refractory DLBCL.

PMID- 29058503
TI  - Development of a rapid and sensitive HPLC method for the identification and
      quantification of cavoxin and cavoxone in Phoma cava culture filtrates.
AB  - Cavoxin is a tetrasubstituted phytotoxic chalcone and cavoxone is the
      corresponding chroman-4-one, both produced in vitro by Phoma cava, a fungus
      isolated from chestnut. Cavoxin showed biofungicide potential against fungal
      species responsible for food moulding. Therefore, cavoxin has potential to be
      incorporated into biopolymer to generate 'intelligent food packaging'. To reach
      this objective, large-scale production of cavoxin by P. cava fermentation needs
      to be optimized. A rapid and efficient method for cavoxin analysis, as well as of
      cavoxone, in the fungal culture filtrates and the corresponding organic extracts
      is the first experimental step. Thus, a HPLC method was developed and applied to
      quantify cavoxin and cavoxone production in two different fungal culture
      conditions. The analysis proved that cavoxin production in stirred culture
      filtrates is significantly higher than in static ones.

PMID- 29058504
TI  - End-of-Life Palliative Care Practices and Referrals in Uganda.
AB  - BACKGROUND: While early involvement and integration of palliative care with
      oncology can positively impact quality of life and survival of patients with
      advanced cancer, there is a dearth of information regarding this integration in
      sub-Saharan Africa. OBJECTIVE: We sought to describe the rate and factors
      predicting specialist palliative referrals among cancer patients in Uganda.
      DESIGN: We examined the rate of referrals of cancer patients to palliative
      specialists via a chart review, while also surveying and interviewing doctors at
      the Uganda Cancer Institute (UCI) about their approaches to palliative care.
      SETTING: All adult patients at the UCI who died in a 20-month interval from 2014
      to 2015. All UCI doctors were approached for the survey and 25 (96%)
      participated. Seven of these doctors were also individually interviewed.
      MEASUREMENTS: Number of referrals to palliative specialists and qualitative
      responses to questions about end-of-life care management. RESULTS: Sixty-six
      (11.1%) of 595 patients were referred to palliative care specialists. Patients
      with worse ECOG performance statuses were more likely to be referred to
      palliative specialists (odds ratio 2.23, p = 0.03); no other factors were
      predictive of a referral. Median number of days lived after referral was 5 days
      (interquartile range 2-13). Doctors explained the low referral rate and short
      life expectancy after referral by limited palliative resources and a reticence to
      have end-of-life management conversations with patients due to cultural taboos.
      CONCLUSION: Despite recognized benefits of palliative collaboration, doctors at
      the UCI seldom refer patients to palliative care specialists due to limited
      staffing, cultural barriers, and difficult interservice communication.

PMID- 29058505
TI  - A case series of anophthalmic socket cysts excised utilising fibrin sealant.
AB  - Anophthalmic socket cysts are challenging to remove and incomplete excision has
      been shown to increase the risk of recurrence. This case series describes a novel
      technique utilising the fibrin sealant Tisseel (Baxter AG, Vienna, Austria) to
      retain the socket cyst integrity during surgical removal to facilitate its
      complete excision. Five patients were included and followed up for a minimum of 1
      year, and there were no signs of recurrence in any of the cases. The surgical
      technique is described and illustrated. This technique is a safe way of
      simplifying challenging socket cyst surgery.

PMID- 29058506
TI  - Adaptation of a Voice-Centered Relational Framework to Explore the Perspective of
      Parents Who Have Transitioned to Home with a Child With Complex Care Needs.
AB  - Parents of children with complex care needs are generally willing to participate
      in research studies about their experiences; however, they are often challenged
      in their capacity to participate as they struggle to find time for family life.
      In our research with parents to explore their experience of transitioning to
      home, we deliberately sought an approach that would reduce the imposition on
      parents, while gaining insightful interpretations of their experiences. This
      article reflects on our experience of the process of discovering, analyzing, and
      interpreting parents' perspectives of their journey to home, when interviewed by
      telephone. Applying the voice-centered relational method of qualitative analysis,
      accounts from parents were explored by the research team using 4 perspectives:
      the plot and evaluator responses to the narrative; the voice of the "I";
      relationships; and placing people within cultural contexts and social structures.
      Parents interviewed were very receptive to being interviewed by phone. We found
      that this enhanced their trust in the interview process and subsequently led to
      our ability to gather rich data. The use of multiple lenses of analysis gave
      insightful interpretations of their journey to home.

PMID- 29058507
TI  - Proximal Predictors of Alcohol Use among Japanese College Students.
AB  - BACKGROUND AND OBJECTIVES: This study investigated how negative social
      interactions (e.g., disagreeing with a friend) predicted subsequent drinking
      behaviors among Japanese college students. Because of social influences on
      drinking, and cultural norms for maintaining social harmony and making amends in
      response to social transgressions in Japanese culture, the authors hypothesized
      that students would consume more alcohol socially following increases in negative
      social interactions. Drinking refusal self-efficacy and social self-efficacy were
      also studied as moderators of social drinking. METHODS: Fifty-five college
      students (79% women) of legal drinking age completed a once-daily Internet survey
      for 30 days, providing 1195 daily reports of drinking and social interaction.
      Prior to the daily survey, participants reported on Drinking Refusal Self
      Efficacy and Social Self-Efficacy in an initial Internet-based assessment.
      RESULTS: Students drank more socially in the evening following daytime increases
      in negative social interactions, relative to evenings following fewer such
      exchanges (b = .23, p < .001). At the between-person level, students who reported
      stronger confidence in refusing to drink drank less socially compared to those
      who reported less confidence in drinking refusal (b = -.53, p < .001). Yet, those
      with higher social self-efficacy, which is typically a health-protective factor,
      drank more socially compared to their counterparts (b = .32, p < .05).
      Conclusions and Importance: Japanese college students increased their social
      drinking in response to daily negative social interactions, consistent with the
      notion that this drinking pattern represents efforts to make amends to others.
      Interventions targeted toward increasing students' confidence in refusing to
      drink may be beneficial in reducing social drinking in this population.

PMID- 29058509
TI  - Assessing an Intervention Focused on Enhancing Interpersonal Communication Skills
      and Humor: A Multi-Method Quasi-Experiential Study Among Medical Students.
AB  - Teaching and applying interpersonal communication skills (ICS) and humor in
      medicine is challenging. The present study assessed an innovative course focused
      on enhancing ICS and humor based on the Four Habits Model and theater concepts.
      Medical students enrolled in the course (the study group) were assessed pre- and
      post-intervention, as well as compared with their peers (the control group) using
      quantitative methods to measure attitudes, self-efficacy, and behaviors.
      Qualitative methods were used to learn about students' change in perceptions
      related to ICS and humor following the course, as well as their experiences of
      developing these skills during the course. Post-intervention study group
      participants scored significantly higher on all ICS measurements and on humor
      behavior compared with pre-intervention, and significantly higher on all humor
      measurements compared with control group participants. Interviews indicated
      students' increased understanding and difficulties in learning these skills.
      Analyses showed how framing humor as one possible ICS and focusing on specific
      parts of the medical encounter can promote patient-centered care.

PMID- 29058508
TI  - Translation and psychometric evaluation of the Swedish version of the
      Interdisciplinary Education Perception Scale.
AB  - Interprofessional education (IPE) is widely accepted worldwide, as a key part of
      training for health professionals and critical to an effective, patient-centred
      healthcare system. Several tools have been developed to evaluate IPE programmes
      and interventions globally. Many of the widely-used tools have been successfully
      adapted to suit specific cohorts and different languages; the Interdisciplinary
      Education Perception Scale (IEPS), however, has not yet been translated and
      validated for use in Sweden. The aim of this study was to translate the IEPS into
      Swedish and validate the psychometric properties of this new version. The 12-item
      IEPS underwent translation into Swedish and back-translation into English by
      suitable independent translators to ensure items retained their meaning. The new
      Swedish version was completed by 164 medical and nursing, occupational therapy
      and physiotherapy students on clinical placements in Stockholm. Principal Axis
      Factoring (PAF) and Oblique Oblimin Rotation confirmed a three-factor structure,
      that explained 77.4% of variance. The new 10-item Swedish version IEPS displayed
      good internal consistency with an overall Cronbach's alpha of a = .88 and
      subscale values of .89, .88 and .66. The exclusion of two-items limits the
      transferability of this scale; however, the factor makeup was very similar to the
      original 12-item English version. It is suspected that minor differences were due
      to unavoidable deviations in meaning following translation (i.e. certain English
      words have no equivalent in Swedish). Nevertheless, the results imply that the
      Swedish version of the IEPS is a valid and reliable tool for assessing students'
      perceptions and attitudes towards IPE within the Swedish health education system.

PMID- 29058510
TI  - Medical student perceptions of an initial collaborative immersion experience.
AB  - Recent reviews of interprofessional education (IPE) highlight the need for
      innovative curricula focused on longitudinal clinical learning. We describe the
      development and early outcomes of the initial clinical experience (ICE), a
      longitudinal practice-based course for first-year medical students. While IPE
      courses focus on student-to-student interaction, ICE focuses on introducing
      students to interprofessional collaboration. Students attend 14 sessions at one
      of 18 different clinical sites. They work directly with different health
      professionals from among 17 possible professions, including nurses, pharmacists,
      social workers, and respiratory, occupational, and physical therapists. Between
      2015 and 2016, 167 students completed the course, and 81 completed the end-of
      course evaluation. Students agreed or strongly agreed that ICE meaningfully
      contributed to their understanding of healthcare teams and different professional
      roles (86%), improved their understanding of healthcare systems (84%), improved
      their ability to communicate with healthcare professionals (61%), and improved
      their ability to work on interprofessional teams (65%). Select themes from
      narrative comments suggest that clinical immersion improves understanding of
      professional roles, helps students understand their own future roles in
      healthcare teams, and increases awareness of and respect for other professionals,
      with the potential to change future practice. ICE may be a template for other
      schools wishing to expand their current educational offerings, by engaging
      learners in more authentic, longitudinal clinical experiences with practicing
      healthcare professionals.

PMID- 29058511
TI  - Pregnancy in a non-communicating rudimentary horn: a cause of failed medical and
      surgical management of second trimester pregnancy loss.
AB  - OBJECTIVES: We present the management of a case of failed medical and surgical
      management of second trimester pregnancy loss due to pregnancy in a non
      communicating rudimentary horn. CASE: A 16-week intrauterine fetal death
      singleton pregnancy was referred to us after failed medical and surgical
      termination of pregnancy. Ultrasound confirmed the diagnosis and showed minimal
      blood clots and fluid in the pouch of Douglas. Laparoscopy showed a soft,
      enlarged right uterine horn not communicating with the cervix and containing the
      pregnancy, and a left uterine horn communicating with the cervix and showing a
      posterior wall perforation. The procedure was converted to laparotomy, and the
      right uterine horn and adjacent tube were excised. The patient made an uneventful
      recovery and was discharged after 3 days. CONCLUSION: Pregnancy in a non
      communicating horn is rare and usually presents with serious complications. Any
      case of failed medical termination of pregnancy after repeated doses of
      misoprostol should be carefully assessed to exclude the possibility of uterine
      anomalies (especially in a primigravida), before proceeding with dilatation and
      evacuation to minimise the risk of complications.

PMID- 29058512
TI  - Maternal serum autotaxin levels in early- and late-onset preeclampsia.
AB  - PURPOSE: We aimed to compare the serum autotaxin levels in early- and late-
      preeclamptic and healthy pregnant patients at a university hospital. METHODS: A
      total of 55 singleton preeclamptic women who delivered at Cerrahpasa Medical
      Faculty were included in the study. The patients were subdivided into two groups:
      early-onset preeclampsia (n = 31) and late-onset preeclampsia (n = 24).
      Demographic and clinical data were compared between early-onset and late-onset
      preeclamptic patients. The control group was composed of 32 healthy pregnant
      patients. RESULTS: The mean autotaxin levels were 1.16 +/- 0.97 and 0.7 +/- 0.35
      ng/ml in the early- and late-onset preeclampsia groups, respectively. Autotaxin
      levels were significantly higher in early-onset preeclampsia group compared with
      late-onset preeclampsia group. Autotaxin levels were found to be significantly
      higher in preeclamptic patients compared with control group. Serum autotaxin
      levels showed a significant positive correlation with maternal systolic,
      diastolic blood pressures and uric acid levels. CONCLUSION: Autotaxin might be a
      promising marker for detecting early-onset preeclampsia. However, further studies
      are necessary to confirm this hypothesis.

PMID- 29058513
TI  - Accurate detection of low-level mosaic mutations in pediatric acute lymphoblastic
      leukemia using single molecule tagging and deep-sequencing.
AB  - Pathogenic mutations in relapse-associated genes in pediatric acute lymphoblastic
      leukemia may improve risk stratification when detected at subclonal levels at
      primary diagnosis. However, to detect subclonal mutations upfront, a deep
      sequencing approach with high specificity and sensitivity is required. Here, we
      performed a proof-of-principle study to detect low-level mosaic RAS pathway
      mutations by deep sequencing using random tagging-based single molecule Molecular
      Inversion Probes (smMIPs). The smMIP-based approach could sensitively detect
      variants with allele frequency as low as 0.4%, which could all be confirmed by
      other techniques. In comparison, with standard deep-sequencing techniques we
      reached a detection threshold of only 2.5%, which hampered detection of seven low
      level mosaic mutations representing 24% of all detected mutations. We conclude
      that smMIP-based deep-sequencing outperforms standard deep-sequencing techniques
      by showing lower background noise and high specificity, and is the preferred
      technology for detecting mutations upfront, particularly in genes in which
      mutations show limited clustering in hotspots.

PMID- 29058514
TI  - Transmissible Plasmids and Integrons Shift Escherichia coli Population Toward
      Larger Multiple Drug Resistance Numbers.
AB  - Transmissible plasmids and integrons may play important roles in the persistence
      and spread of antibiotic-resistant bacteria throughout aquatic environment by
      accumulating antibiotic resistance genes (ARG). Class 1 and class 2 integron
      (intI), mobilization (mob), sulfamethoxazole resistance (sul), and trimethoprim
      resistance (dfr) genes were PCR-amplified and confirmed through DNA sequencing
      following plasmid extraction from 139 antibiotic-resistant Escherichia coli. E.
      coli had previously been recovered from wastewater treatment plant effluent and
      receiving stream water in Northwest Arkansas and isolates had expressed
      resistance to one to six antibiotics. Almost half of the total isolates (47%)
      carried putatively transmissible plasmids with mobF12 gene as the most frequently
      detected mobilization gene. When two or three mob genes were detected per
      isolate, there was a significant shift in the population toward larger multiple
      drug resistance (MDR) number. Class 1 and/or 2 integrons were prevalent (46%),
      and the presence of integron significantly shifted the isolate population toward
      larger MDR number. More isolates carried single or coexistence of two or three
      sul genes (99.3%), and single or a combination up to five dfr genes (89.3%) than
      had exhibited in vitro resistance to the respective antibiotics. These findings
      indicate not only the role of the wastewater treatment effluent and the stream
      environment in coaccumulation of ARG with transmissible plasmids and integrons in
      multiple antibiotic-resistant E. coli populations but also suggest that density
      of sul and dfr resistance genes within an isolate may serve as a biomarker for
      mobile MDR in general.

PMID- 29058515
TI  - Prevalence and Molecular Characterization of New Delhi Metallo-Beta-Lactamases in
      Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii from
      India.
AB  - New Delhi metallo-beta-lactamase (NDM)-mediated carbapenem resistance in
      Pseudomonas aeruginosa and Acinetobacter baumannii is a major concern. We
      investigated the presence of NDM and its variants in P. aeruginosa and A.
      baumannii at a tertiary hospital in North India. A total of 236 isolates (130 P.
      aeruginosa and 106 A. baumannii) were included; 38 (29.23%) P. aeruginosa and 20
      A. baumannii isolates (18.8%) were resistant to carbapenems and all of them were
      blaNDM positive. All 38 carbapenem-resistant P. aeruginosa harbored blaNDM-1,
      while 12 (60%) of 20 A. baumannii harbored blaNDM-2. Pulsed-field gel
      electrophoresis showed that all 58 isolates were clonally unrelated. By Southern
      blot analysis, blaNDM-2 was located on chromosome. The blaNDM-2-positive isolates
      were more frequently recovered from tracheal aspirate (67% vs.16%; p = 0.02) and
      intensive care unit (67% vs. 20%; p = 0.001) than blaNDM-1. Among other
      carbapenemases, VIM was significantly associated with blaNDM-1 than blaNDM-2 (61%
      vs. 17%; p = 0.006). Mortality between blaNDM-1- and blaNDM-2-infected patients
      was comparable. When expressed in Escherichia coli, blaNDM-2 transformant
      conferred one doubling dilution higher MIC value for cefotaxime,
      piperacillin/tazobactam than blaNDM-1. The study shows the emergence of blaNDM
      mediated resistance among P. aeruginosa and A. baumannii and rapid evolution of
      blaNDM-2 in A. baumannii with its chromosomal localization.

PMID- 29058516
TI  - Clinician-initiated research on treating the host response to pandemic influenza.
AB  - To prepare for the next influenza pandemic and other emerging virus diseases,
      scientists and health officials are focused on developing new vaccines and
      treatments that target these viruses. Ideally, these interventions could be
      highly effective, but for many practical reasons these "top down" efforts are
      unlikely to provide clinicians with what they will need to manage their patients.
      As a "bottom up" alternative, combinations of generic drugs like statins and
      angiotensin receptor blockers (ARBs) might be used to treat the host response to
      infection. These drugs counteract endothelial dysfunction, a central abnormality
      in these diseases. Observational studies in patients with influenza, pneumonia,
      sepsis and Ebola suggest they might work. During the 1918 influenza pandemic,
      children were infected more frequently than adults, but their mortality rate was
      much lower. Their survival was probably due to better tolerance (reduced pathogen
      damage), not greater resistance (reduced pathogen burden). The same pattern of
      susceptibility characterizes other infectious diseases, and it probably reflects
      the heritage of human evolution. Drugs like statins and ARBs can metabolically
      reprogram the host response and improve tolerance to infection. Treating the host
      response is not on the research agendas of international agencies responsible for
      pandemic preparedness. Consequently, clinicians might have to undertake clinical
      trials in patients hospitalised with seasonal influenza, pneumonia and sepsis in
      order to show convincingly whether treating the host response would work. Most
      candidate generic drugs are inexpensive, widely available, known to be safe and
      used by clinicians every day. Demonstrating their efficacy would mean that
      patients in all countries would have access to treatment on the first pandemic or
      epidemic day.

PMID- 29058517
TI  - Abducens nerve palsy after orbital decompression.
AB  - INTRODUCTION: Double vision after decompression surgery for Thyroid Eye Disease
      (TED) is well described in the literature and the incidence ranges from 0 to 64%.
      The Mechanisms for new onset diplopia after orbital decompression are poorly
      understood. Common theories include: Fibrosis of muscles, displacement of the
      muscle cone, and reactivation of the TED. AIM: We present two cases with Abducens
      nerve palsy after uncomplicated secondary orbital decompression surgery. RESULTS:
      Two patients with inactive TED, who were followed for an average of 2 years prior
      to uneventful secondary decompression surgery, presented at the first
      postoperative visit with double vision and limitation of abduction in the
      recently operated eye. Magnetic resonance imaging(MRI) was done in both cases and
      revealed no abnormal bleeding or scaring. DISCUSSION: Our two cases of Abducens
      palsy following reoperative orbital decompression may be due to ischemic
      neuropathy caused by postoperative hemorrhage or inflammation.

PMID- 29058518
TI  - Recent Evidence on the Inclusion of Hospice and Palliative Care Physicians in
      Medicare Shared Savings Program Accountable Care Organization Networks.
AB  - OBJECTIVE: To document the presence of hospice and palliative physicians in
      Medicare Shared Savings Program (MSSP) ACOs. BACKGROUND: End-of-life care
      exhibits extreme variation in quality, cost, and patient experience. This
      baseline creates opportunities for improvements that would be financially
      rewarded in the new value-based reimbursement environment, such as the
      accountable care organization (ACO) model. Little is known about how ACOs have
      responded to this opportunity by including hospice and palliative providers in
      their formal provider networks. DESIGN: This is a cross-sectional analysis of
      2014 MSSP ACO provider networks assessing inclusion of a hospice or palliative
      physician. SETTING/SUBJECTS: This study included MSSP ACO provider networks.
      RESULTS: Approximately three-quarters of MSSP ACOs did not formally contract with
      a hospice or palliative care physician in 2014. Inclusion of a hospice or
      palliative physician was associated with other specialists that commonly refer to
      hospice and palliative care, such as oncologists. DISCUSSION: By rewarding
      innovation that lowers expenditures, the ACO model encourages attention to care
      that exhibits high variation and expense. Both hospice and palliative care have
      been shown to reduce costs and improve the patient experience, making them
      potentially powerful tools in an ACO's arsenal. However, the MSSP ACO model has
      not emphasized care of seriously and terminally ill individuals, and thus it is
      not surprising that there has been consistently low inclusion of hospice and
      palliative care physicians in MSSP provider networks.

PMID- 29058520
TI  - Multiresidue method for detection of pesticides in beef meat using liquid
      chromatography coupled to mass spectrometry detection (LC-MS) after QuEChERS
      extraction.
AB  - Beef meat is an important food that can be contaminated by pesticides. This study
      aimed to optimize a multiresidue method for identification and quantification of
      pesticides in beef meat by liquid chromatography coupled to mass spectrometry
      detection (LC-MS). The extraction and clean-up procedures were adapted from the
      QuECHERS method. From the 188 analytes tested, the method was validated as
      qualitative method for 19 compounds and as quantitative method for 152 compounds.
      The results were satisfactory, yielding coefficients of variation of less than
      20% and recoveries ranging from 70% to 120% and expanded uncertainty of less than
      50%. The quantification limit was typically 10 ug kg-1 (but 25 ug kg-1 for 12 of
      the compounds) and the detection limit was 5.0 ug kg-1. Thirty-two real samples
      of commercialized beef meat were analyzed without any residual pesticide being
      found. Thus, the results showed that the multiresidue method for detecting 171
      pesticides, using adapted QuECHERS for extraction and LC-MS for detection, is
      suitable for analyzing beef meat.

PMID- 29058519
TI  - Longitudinal changes in cognition in young adult cannabis users.
AB  - INTRODUCTION: Adolescent cannabis use (CU) is associated with impaired attention,
      executive function, and verbal learning/memory. These associations are generally
      observed in cross-sectional studies. Longitudinal studies of cannabis users are
      lacking. METHOD: The present study examines associations between CU and cognition
      over time in chronic daily adolescent-onset CUs, as compared to nonusing
      controls. Both groups completed a neuropsychological battery at study intake and
      again 2 years later. RESULTS: Baseline group differences have been published and
      indicated deficits in verbal learning and memory, motivated decision-making,
      planning, and working memory in CUs. In this follow-up report, the longitudinal
      performance of users is compared to that of sustained nonusers using the same
      battery. At follow-up, the majority of CUs continued to report regular and heavy
      cannabis use. Relative impairments in the domains of working memory, planning and
      verbal memory remained stable, suggesting that these are enduring vulnerabilities
      associated with continued CU during young adulthood. Improvements in motivated
      decision-making were evident in both groups. In addition, CUs demonstrated
      relatively better performance on short-duration speeded tasks. An earlier age of
      CU onset was associated with poorer verbal learning and memory and planning
      performance over time. CONCLUSIONS: Verbal learning and memory and planning
      processes, as well as their neural correlates, merit further scrutiny within
      etiological models of cannabis-induced cognitive impairments.

PMID- 29058522
TI  - A new surgical technique for congenital distichiasis.
AB  - PURPOSE: To describe a new technique to treat congenital distichiasis. METHODS:
      Case series of three distichiatic patients undergoing a novel surgical technique
      combining splitting of the lid margin with the distichiatic lashes, marginal
      tarsectomy in the affected area, and tarsoconjunctival graft obtained from the
      upper region of the tarsus. The graft was sutured at the exposed region of the
      marginal tarsectomy. RESULTS: Good cosmesis was obtained in all cases and the
      lids margins healed completely with good surgical outcome and no lashes contacted
      the cornea postoperatively. CONCLUSIONS: The split lamellae with a composite
      tarsoconjunctival graft results in satisfactory functional and cosmetic outcomes.
      The upper tarsal region represents an ideal donor site.

PMID- 29058523
TI  - Orbitofacial dermatofibrosarcoma protuberans with intranasal extension.
AB  - A 25-year-old Chinese woman presented with recurrent painless swelling over the
      left medial canthus region for 3 months and intranasal mass for an indeterminate
      duration. Initial incision biopsy of the mass was reported as nodular fasciitis
      but the lesion recurred 3 weeks later. Intraoperative findings during repeat
      biopsy showed a mass extending from the deep dermal tissue into the anterior
      orbit and polyp-like nasal mass. Histopathology findings were that of
      dermatofibrosarcoma protuberans (DFSP). The mass recurred 4 months later without
      orbital or intranasal recurrence. Wide excision biopsy under frozen section
      guidance was attempted however; clear surgical margins could not be achieved
      despite extensive resection. She was subsequently referred for adjuvant
      radiotherapy. We report an exceptionally rare case of local recurrence of DFSP in
      an unusual anatomic location. This case was surgically challenging in achieving
      negative margins, and thus neoadjuvant therapy may improve overall outcome to
      prevent local relapse.

PMID- 29058521
TI  - Examining the Validity of Self-reported Primary and Secondary Exposure to
      Cigarette Smoke in Adolescent Girls: The Utility of Salivary Cotinine as a
      Biomarker.
AB  - BACKGROUND: Studies of cigarette use and exposure often rely on either self
      report or cotinine assay. In adolescence it is not clear how well assays and self
      report correspond, or what effect estrogen exposure has on cotinine. OBJECTIVES:
      This study sought to identify optimal cut-points for salivary cotinine thresholds
      for girls with primary, secondary, and no smoke exposure, and whether menarche
      and hormone contraceptive use are important for interpreting salivary cotinine.
      METHODS: This longitudinal prospective study recruited 262 healthy adolescent
      girls who participated in three annual interviews across 24 months. Salivary
      cotinine assays and self-report of primary and secondary smoke exposure,
      menarcheal status, and hormone contraceptive use were collected. RESULTS: No
      adolescents reported primary smoke exposure without secondary exposure. Optimal
      cut-points for distinguishing primary smoke exposure from secondary-only and no
      smoke exposure were 1.05 and 3.01 ng/ml, respectively based on receiver operator
      curves (ROC); no reliable cut-point for secondary-only versus no smoke exposure
      was identified. The ideal salivary cotinine cut-point to distinguish primary
      smoke exposure varied by hormone contraceptive use and was 2.14 ng/ml for those
      using progesterone contraceptives, higher than that of girls using estrogen
      contraceptives and those not using hormone contraceptives. CONCLUSIONS: This
      study is the first to examine variance in salivary cotinine cut-points based on
      hormone exposure for adolescent girls, with findings indicating that hormone
      contraceptive use in particular may be a key consideration when identifying
      adolescent smoking. The use of previously recommended salivary cotinine cut
      points of 3.85 ng/ml or higher may overestimate nonsmokers.

PMID- 29058524
TI  - Considerable interest in pre-exposure prophylaxis uptake among men who have sex
      with men recruited from a popular geosocial-networking smartphone application in
      London.
AB  - Men who have sex with men (MSM) who use smartphone applications (apps) to meet
      sexual partners represent a high-risk subset of MSM. As such, the use of pre
      exposure prophylaxis (PrEP) may be highly suitable. The purpose of the study was
      to evaluate awareness of and willingness to use PrEP among 179 HIV-uninfected MSM
      recruited in London who use these apps. Regression models were fit to assess the
      associations between perceived barriers and willingness to use PrEP in the
      future. Most (84.9%) had heard of PrEP and more than half (57.1%) were willing to
      use PrEP in the future if it were to become available. Low perceived risk for
      acquiring HIV (prevalence ratio (PR): 0.11; 95% confidence interval (CI): 0.04,
      0.33) and concerns about PrEP-related side effects (PR: 0.01; 95% CI: 0.00, 0.04)
      were associated with being unwilling to use PrEP. Efforts to make PrEP widely
      available should be continued. Uptake interventions should focus on correcting
      self-perceptions of HIV risk and educate MSM about the potential side effects of
      PrEP use so that MSM can make more informed decisions about prevention options.

PMID- 29058525
TI  - Caregiving Load and Respite Service Use: A Comparison between Older Caregivers
      and Younger Caregivers.
AB  - Study aims were to explore differences in predictors of respite care use between
      older (aged 65+) and younger caregivers (aged 18-64 years), and associations
      between caregiving load and respite care use using multivariate logistic
      regression analysis and unpaid caregiver (n= 10,500) data from the 2009
      California Health Interview Survey. Caregiving load comprised number of care
      recipients, weekly hours in caregiving, and caregiving duration. Variables with a
      significant association with respite care for older caregivers were female
      gender, income, and health insurance. For younger caregivers, respite care use
      associations were with ethnicity, caregiving relationship, education, and
      availability of substitute help.

PMID- 29058526
TI  - Mycobacterium tuberculosis of the Beijing Genotype in Iran and the World Health
      Organization Eastern Mediterranean Region: A Meta-Analysis.
AB  - OBJECTIVE: The Beijing genotype is a distinct genetic lineage of Mycobacterium
      tuberculosis, which is distributed worldwide, and may cause large outbreaks of
      multidrug resistance-tuberculosis (MDR-TB). The distribution of such strains in
      the Eastern Mediterranean region (EMR) is unclear, and clarifying the data is our
      purpose apart from the presence of Beijing TB in Iran. METHODS: We searched
      Published literature from CINAHL Cochrane Library, Current Contents, Database of
      Abstracts of Reviews of Effects (DARE), ProQuest Google Scholar PubMed, PsycINFO,
      Thomson Reuters, (SID), and Medical Library (MedLib) to detect relevant studies
      from the year 2000 to July 2015 with the following keywords: M. tuberculosis,
      Beijing genotype, EMR, and drug resistance. Random-effect models were used to
      estimate the proportion of Beijing strains in STATA 14. Heterogeneity was
      investigated by subgroup analysis and meta-regression. RESULTS AND CONCLUSION:
      The meta-prevalence of Beijing strains was 4% (CI 95% = 3-5). The prevalence was
      different based on types of detection techniques (spoligotyping = 4% vs. other
      techniques = 6%; p = 0.003) and years of study (before the year 2000 = 2% vs.
      after year 2000 = 4%, p = 0.004). The Beijing family was most prevalent in Iran
      and Pakistan. A strong relationship with drug resistance was reported in Pakistan
      and Iran, and an increasing trend was seen in Pakistan. Additional studies of
      drug-resistant TB distribution among Beijing strains in EMR countries are needed
      as well as a time-trend analysis of the Beijing strain infection in the region.

PMID- 29058527
TI  - Gender differences in prevalence and correlates of high sexual self-efficacy
      among adolescents in Soweto, South Africa: implications for gender-sensitive
      research and programming.
AB  - Sexual self-efficacy (SSE) - one's confidence in their ability to perform given
      sexual behaviours, has been shown to predict adolescents' HIV-prevention
      practices (e.g., Condom use). Few studies within sub-Saharan Africa, where HIV
      incidence and prevalence disproportionately affects young women, have examined
      gendered differences in SSE. We used multivariable logistic regression to
      identify correlates of high-SSE separately among adolescent men and women (aged
      14-19) in Soweto, South Africa using a previously validated SSE scale (high-SSE
      [>3/6 items]; study-alpha = 0.75). SSE scale items assessed self-efficacy related
      to sexual refusal and condom use. Adolescent women were significantly more likely
      to report high-SSE than adolescent men (72.3% versus 49.5%; p < 0.01). High-SSE
      among adolescent men was associated with more positive beliefs about sexual
      relationships and negatively associated with probable depression. High-SSE among
      adolescent women was associated with increased HIV knowledge, more positive
      beliefs about condom use and sexual relationships, having an adult in the home,
      and negatively associated with being an older adolescent (16-17 versus <=15), and
      ever experiencing physical violence. Differences in prevalence and correlates of
      SSE among adolescent men and women in South Africa highlight important areas for
      gender-sensitive interventions. Targeted efforts to reduce negative sexual
      beliefs, improve HIV knowledge and mental well-being may improve SSE and thus the
      uptake of HIV-prevention practices among adolescent men. For adolescent women,
      findings indicate programming should move beyond individual-levels determinants
      of behaviour to focus on improving enabling environments (e.g., Reduced violence
      and improved family relationships) in which sexual agency can be enacted.

PMID- 29058529
TI  - Social Support and Self-Rated Health of African American Women Informal
      Caregivers: Urban and Rural Differences.
AB  - In this study, we examined how geographic location might differently influence
      social support and self-rated health for rural and urban African American women
      caregivers. We used cross-sectional data from 253 urban and 263 rural women
      primary caregivers. Controlling for key demographic factors, we regressed
      caregivers' self-rated health on social engagement, structural, and functional
      aspects of social support for urban and rural caregivers separately. The
      perception of family functioning was positively associated with urban and rural
      caregivers' self-rated health. Urban caregivers reported having significantly
      more contact with their family and more informal helpers compared to rural
      caregivers. Furthermore, church attendance, a measure of social engagement, was
      significant for urban caregivers' self-rated health, but not rural caregivers.
      Our findings affirmed the importance of foregrounding context and disaggregating
      social support, and point to the need for interventions targeting family
      functioning and paying attention to geographic location.

PMID- 29058528
TI  - Clinical Q & A: Translating Therapeutic Temperature Management from Theory to
      Practice.

PMID- 29058530
TI  - Australian Queer Science Fiction Fans.
AB  - Science fiction (sf) does more than provide a fleeting moment of entertainment;
      it has many personal and social functions. In addition to offering audiences
      "romantic escapism" (Gerrold, 1996, pp. 5-6), sf also enables the "postulation of
      an alternative reality from which to contemplate this one" (Gerrold, 1996, pp. 5
      6); as such, it is especially important "for groups which have had limited stakes
      in the status quo" (Jenkins, 1995, p. 242). To date, no research has been
      undertaken on the relationship between Australian queers and sf fandom. This
      article reports the findings of an online survey and explores the psycho-social
      features of Australian queer sf fans and why they like the genre. While the
      characteristics of this sample mirror those of Australian queers generally, they
      also have slightly higher rates of mental illness and are far more likely to
      state they have "no religion." Furthermore, while enjoying the "sciency" (P10,
      bisexual woman) aspects of sf, Australian queers also like the "poignant
      metaphors for our own civilization" (P45, asexual man).

PMID- 29058531
TI  - Biophysical and computational comparison on the binding affinity of three
      important nutrients to beta-lactoglobulin: folic acid, ascorbic acid and vitamin
      K3.
AB  - Small globular protein, beta-lactoglobulin (betaLG), which has significant
      affinity toward many drugs, is the most abundant whey protein in milk. In this
      study, the interaction of betaLG with three important nutrients, ascorbic acid
      (ASC), folic acid (FOL), and vitamin K3 (VK3) was investigated by spectroscopic
      methods (UV-visible and fluorescence) along with molecular docking technique. The
      results of fluorescence measurements showed that studied nutrients strongly
      quenched betaLG fluorescence in static (FOL and ACS) or static-dynamic combined
      quenching (VK3) mode. The values of binding constants (KbetaLG-ASC ~ 4.34 * 104 M
      1, KbetaLG-FOL ~ 1.67 * 104 M-1and KbetaLG-VK3 ~ 13.49 * 104 M-1 at 310 K)
      suggested that VK3 and FOL had stronger binding affinity toward betaLG than ASC.
      Thermodynamic analysis indicated that hydrophobic interactions are the major
      forces in the stability of FOL-betaLG complex with enthalpy- and entropy-driving
      mode while, hydrogen bonds and van der Waals interactions play a major role for
      betaLG-ASC and betaLG-VK3 associations. The results of 3D fluorescence FT-IR and
      UV-Visible measurements indicated that the binding of above nutrients to betaLG
      may induce conformational and micro-environmental changes of protein. Also, there
      is a reciprocal complement between spectroscopic techniques and molecular docking
      modeling. The docking results indicate that the ASC, FOL, and VK3 bind to
      residues located in the subdomain B of betaLG. Finally, this report suggests that
      betaLG could be used as an effective carrier of above nutrients in functional
      foods.

PMID- 29058532
TI  - "Will they be good enough parents?": Ethical dilemmas, views, and decisions among
      assisted reproductive technology (ART) providers.
AB  - BACKGROUND: Many adults may make less-than-ideal parents, but important ethical
      questions arise concerning whether assisted reproductive technology (ART)
      providers should thus ever refuse treatment to certain patients, and if so, when,
      and how to decide. METHODS: In-depth interviews of approximately 1 hour each were
      conducted with 27 ART providers (17 physicians, and 10 other health providers).
      RESULTS: Clinicians often struggle with whether to attempt to assess and predict
      patients' potential future parenting abilities, and if so, how, and how to
      proceed if doubts arise. Providers face profound ethical tensions between adults'
      rights to reproduce and best interests of the eventual children (i.e., to be born
      into "stable" homes), and questions about the extent of professional
      responsibilities toward potential parents versus toward future offspring.
      Providers generally feel uncomfortable with this role, and hence don't want it,
      partly since they lack training for it, but also because of inherent empirical
      and ethical uncertainties. Concerns about discrimination based on the mere
      presence or history of certain diagnoses or traits (e.g., single marital status
      or past depression) also arise. Clinicians frequently seek to resolve these
      tensions through various strategies-for example, referring these decisions to
      others; hoping that patients drop out of treatment; assessing and increasing
      social support (e.g., arranging for possible co-parents); assisting the patient
      psychotherapeutically; or seeking to communicate concerns to patients only
      indirectly or implicitly. Clinics vary in how they make and approach these
      decisions-whether they rely on a formal ethics or other committee. CONCLUSIONS:
      These data, the first to explore several critical aspects of in vitro
      fertilization (IVF) providers' views and decision making about assessing the
      quality of patients' potential future parenting, have critical implications for
      future practice, education, research, and guidelines. Further empirical and
      normative scholarship and guidelines are needed to help clarify expectations,
      processes, and possible approaches to aid providers and patients.

PMID- 29058533
TI  - Exploring undergraduate students' attitudes towards interprofessional learning,
      motivation-to-learn, and perceived impact of learning conflict resolution skills.
AB  - Conflict resolution skills are important for all healthcare professionals as
      conflict and mis-communication can have detrimental effects on decision-making,
      potentially impacting significantly on patient care, morbidity, and mortality.
      Interprofessional learning (IPL) has been found to increase collaboration and
      improve collegial relationships and hence may be an appropriate way to increase
      conflict resolution skills among healthcare graduates. This study examined
      transference of conflict resolution skills, motivation-to-learn, and attitudes to
      IPL of medical (n = 52) and nursing (n = 74) undergraduate students who undertook
      an IPL conflict resolution program. Results indicated that motivation-to-learn,
      attitudes to IPL, and transfer of conflict resolution skills were significantly
      related to each other, even when controlling for other variables, such as age and
      gender. When comparing the two groups, undergraduate nursing students were found
      to have statistically higher motivation-to-learn and transference of conflict
      resolution skills, and reported a more positive attitude to IPL than medical
      students. Some of these differences may be attributed to lack of clinical
      placements for medical students in the first half of their degree at their
      university, giving them less opportunity to apply the conflict resolution skills
      taught, as well as less contextual relevance. This may potentially affect their
      motivation-to-learn and attitude to IPL thus impacting on how they perceive the
      relevance of learning conflict resolution skills. Without the contextual
      relevancy of placements at the time of learning for medical students, the newly
      acquired conflict resolution skills are less likely to transfer to practice in an
      optimal fashion.

PMID- 29058534
TI  - Comparative assessment of respiratory and other occupational health effects among
      elementary workers.
AB  - OBJECTIVE: This study was conducted to assess hazards faced by elementary
      workers. METHODS: A questionnaire survey and a respiratory function test
      (spirometry) were carried out on 150 respondents. RESULTS: Major hazards
      identified related to sharp objects, heavy weight lifting, thermally harsh
      conditions, working at height, whole body vibration, chemicals, pathogens,
      increased noise levels and confined space entry. Workers suffered from upper and
      lower respiratory disorder symptoms, digestive problems, optical and
      musculoskeletal issues, etc. Spirometric measurement showed obstructive lung
      disorders to be highest among construction workers (CW) (48%) followed by
      sanitation workers (SW) (32%) and solid waste pickers (SWP) (28%). Restrictive
      lung pattern was dominant among SW (56%) followed by SWP (46%) and CW (42%). The
      observed FEV1/FVC in diseased SWP, SW and CW ranged from 51 to 96%, from 52 to
      98% and from 31 to 99% respectively while observed mean FEV1 was 2.15, 1.79 and
      1.70 L, respectively. CONCLUSION: The study findings show that occupational
      exposure can significantly influence respiratory system impairment and contribute
      to other ailments among elementary workers. The study recommends use of
      appropriate protective equipment and regular medical examination for early
      recognition of any health risk so that timely interventions for effective
      management may be undertaken.

PMID- 29058535
TI  - Transplanting the Body: Preliminary Ethical Considerations.
AB  - A dissociated area of medical research warrants bioethical consideration: a
      proposed transplantation of a donor's entire body, except head, to a patient with
      a fatal degenerative disease. The seeming improbability of such an operation can
      only underscore the need for thorough bioethical assessment: Not assessing a case
      of such potential ethical import, by showing neglect instead of facing the issue,
      can only compound the ethical predicament, perhaps eroding public trust in
      ethical medicine. This article discusses the historical background of full-body
      transplantation, documents the seriousness of its current pursuit, and builds an
      argument for why prima facie this type of transplant is bioethically distinct.
      Certainly, this examination can only be preliminary, indicating what should be a
      wide and vigorous discussion among practitioners and ethicists. It concludes with
      practical suggestions for how the medical and bioethics community may proceed
      with ethical assessment.

PMID- 29058536
TI  - Reactions to Transgender Women and Men in Public Restrooms: Correlates and Gender
      Differences.
AB  - This study examined reactions to transgender people in public restrooms.
      Participants (n = 158) completed measures of essentialism and trait aggression
      and read scenarios where they imagined sharing a restroom with a transwoman or a
      transman. Participants indicated which restroom targets should use and rated
      potential negative reactions. Results indicate that targets were assigned to
      restrooms corresponding to birth sex rather than chosen identity. Women's
      reactions to transgender women were more negative than men's; men were more
      negative in reactions toward transmen. Essentialism predicted some (but not all)
      reactions for all participants. Among women, trait aggression predicted negative
      reactions, but only to transmen. Among men, aggression predicted negative
      reactions, but only toward transwomen. This suggests that despite views that
      transgender people belong in birth-sex restrooms, men and women's trait
      aggression predicts negative reactions toward them in such instances.

PMID- 29058537
TI  - The Influence of an Acute Bout of Whole Body Vibration on Human Postural Control
      Responses.
AB  - The use of vibrating platforms has become increasingly available, and popular at
      sports and rehabilitation institutes. Given the discrepancies in the literature
      regarding whole body vibration (WBV) and human reflexive responses, the purpose
      of this study was to examine the acute effects of WBV on postural response
      latencies, as well as associated electromyography measures of the lower
      extremities during balance perturbations. Reflexive responses during backward and
      forward balance perturbations were examined before, after, and 10 min after a
      bout of WBV. The findings suggest that following an acute bout of whole body
      vibration, muscle activity of the lower extremities is decreased during a
      reflexive response to an unexpected perturbation, and may be associated with
      faster reaction time.

PMID- 29058538
TI  - Down Syndrome and Alzheimer's Disease: Issues and Implications for Social Work
      Practice.
AB  - Owing to recent medical advancements, people with Down Syndrome (DS) are now able
      to live considerably longer lives and thus experience a variety of complex issues
      as they age. Alzheimer's Disease (AD) frequently occurs in older adults who have
      DS, but few practice guidelines exist to inform social work practice with older
      adults who have this dual diagnosis. This commentary will highlight the
      connection between these two conditions within a neurobiological framework and
      discuss implications for practice based on the available literature on this
      intersection of ability status, cognitive status, and age.

PMID- 29058539
TI  - Belgian consensus statement on the diagnosis and management of patients with
      atypical hemolytic uremic syndrome.

PMID- 29058540
TI  - In vivo toxicity assessment of aflatoxin B1-contaminated corn after ozone
      degradation.
AB  - Corn is an important food and feedstuff in China and worldwide. The problems
      caused by aflatoxin B1-contaminated corn (ACC) are of great concern. Our previous
      studies have demonstrated that ozone can effectively degrade AFB1 in corn,
      prompting us to investigate the in vivo toxicity of treated ACC. In this study,
      35 Kunming mice were used to assess the in vivo toxicity of ozone treated ACC.
      Results indicated that compared to mice fed with basal feedstuff (provided by the
      Shanghai SLAC Laboratory), those fed with ACC have significantly decreased mean
      weight as well as total protein (TP), albumin (ALB), and globulin (GLB) contents
      (p < 0.05). On the other hand, the liver and kidney/body weight ratio as well as
      the serum alanine transaminase (ALT), aspartate aminotransferase (AST), and
      alkaline phosphatase (ALP) levels significantly increased (p < 0.05). Obvious
      histopathological changes were found in the liver and kidney. When mice were fed
      with the ozone-treated ACC, no significant differences were observed in the mean
      weight, the liver and kidney/body weight ratio and in the major serum indexes
      ALT, TP, ALB, and GLB (p > 0.05). However, AST and ALP significantly increased (p
      < 0.05), and slight histopathological changes were found in liver tissues. This
      study indicated that ACC may lead to significant changes in various physiological
      characteristics and biochemical indexes in liver and kidney tissues, but ozone
      treatment of ACC could significantly reduce these changes.

PMID- 29058541
TI  - Anesthetic Immunomodulation of the Neuroinflammation in Postoperative Cognitive
      Dysfunction.
AB  - Postoperative delirium and cognitive dysfunction are phenomena that are
      associated with increases in morbidity, mortality, and resource utilization after
      surgery. This review scrutinized a number of studies in order to better
      characterize the biochemical basis for associated cognitive dysfunction and
      delirium, with particular focus paid to the interactions of the cholinergic
      system with innate immunity and how the modulation of the immune system
      contributes to associated neuroinflammation. Despite the clinical impact of
      postoperative cognitive dysfunction, evidence-based protocols for the prevention
      and treatment of these disorders are still lacking. Several previous trials have
      attempted to prevent or treat clinical manifestation by modulation of the
      cholinergic system with acetylcholinesterase inhibitors, the results of which
      have been largely ambiguous at best. As the biochemical basis of postoperative
      cognitive dysfunction becomes more clearly defined, future research into
      therapeutics based on immune modulation and treatment of neuroinflammation may
      prove to be very promising.

PMID- 29058542
TI  - Regulatory roles of micro-RNAs in T cell autoimmunity.
AB  - MicroRNAs (miRNAs) are short conserved non-coding RNA molecules that have
      recently emerged as post-transcriptional gene expression regulators. miRNAs
      degrade or repress target mRNAs by targeting the 3' UTR region. miRNA-mediated
      gene regulation is crucial for regular biological processes such as immune cell
      lineage commitment, differentiation, maturation, and maintenance of immune
      homeostasis and regular function. Changes in miRNA expression patterns have been
      recorded in a wide range of human diseases, including autoimmunity, especially in
      T cell-related autoimmunity. This review discusses recent progress in miRNA
      mediated regulation of T cell-related autoimmunity. Specifically, we discuss the
      modality of T cell-related autoimmunity regulation by miRNAs through affecting
      molecular and biological processes.

PMID- 29058543
TI  - Letter from the Editor 2017.

PMID- 29058544
TI  - Immunomodulatory Effects of Antimicrobial Drugs.

PMID- 29058545
TI  - MicroRNAs in the Diagnosis and Treatment of Cancer.
AB  - Immune cells are recruited into the tumor microenvironment and regulate anti- and
      pro-tumor signals. MicroRNAs (miRNAs) markedly control the immune system
      responses in cancer development. miRNAs that affect the immune system could be
      interesting targets for immunomodulation against cancer, either through the
      activation of effector cells or through the down-regulation of regulatory cells.
      Bioinformatic calculations can predict the immune system and miRNA interactions.
      In this review, we discuss the most recent studies about miRNA as the main
      regulator of recruitment and the activation of the immune system in the tumor
      microenvironment and finally we propose several miRNAs that could serve as
      therapeutic molecules in the immunotherapy of cancer.

PMID- 29058546
TI  - Immunomodulatory interplay of the microbiome and therapy of rheumatic diseases.
AB  - Modulation of the immune system by microbes, especially from the gastrointestinal
      tract, is increasingly considered a key factor in the onset, course and outcome
      of rheumatic diseases. The interplay of the microbiome, along with genetic
      predisposition and environmental exposure, is thought to be an important trigger
      for rheumatic diseases. Improved identification of the relationship of disease
      specific genetic alterations and rheumatic diseases has potential diagnostic and
      therapeutic applications. Treatment of rheumatic disorders is influenced by
      microbial actions but this interplay can be challenging due to variable and
      unpredictable responses to therapies. Expanded knowledge of the microbiome now
      allows clinicians to more precisely select ideal medication regimens and to
      predict response to and toxicity from drugs. Rheumatic diseases and associated
      therapies were among the earliest microbiome interactions investigated, yet it is
      notable that current research is focused on clinical and immunological
      associations but, in comparison, a limited number of studies regarding the
      microbiome's impact on treatment for rheumatic diseases have been published. In
      the coming years, further knowledge of immunomodulating interactions between the
      microbiome and the immune system will aid our understanding of autoimmunity and
      will be increasingly important in selection of therapeutic agents for patients
      with autoimmune and rheumatic diseases. In this review, recent literature
      regarding the bidirectional immunomodulatory effects of the microbiome with
      rheumatic diseases and current understanding and gaps regarding the drug
      microbiome interface in the management of these disorders is presented.

PMID- 29058548
TI  - Immunomodulation Mechanisms in Disease and in the Surgical Patient.

PMID- 29058547
TI  - Volatile Anesthetics and Immunity.
AB  - Historically, volatile anesthetics have demonstrated interesting interactions
      with both the innate and adaptive immune systems. This review organizes these
      interactions into four phases: recognition, recruitment, response, and
      resolution. These phases represent a range of proinflammatory, inflammatory, and
      innate and adaptive immune regulatory responses. The interaction between volatile
      anesthetics and the immune system is discussed in the context of pathogenesis of
      infectious disease.

PMID- 29058550
TI  - Immunomodulatory Role of Complement Proteins in the Neuropathology Associated
      with Opiate Abuse and HIV-1 Co-Morbidity.
AB  - The complement system which is a critical mediator of innate immunity plays
      diverse roles in the neuropathogenesis of HIV-1 infection such as clearing HIV-1
      and promoting productive HIV-1 replication. In the development of HIV-1
      associated neurological disorders (HAND), there may be an imbalance between
      complement activation and regulation, which may contribute to the neuronal damage
      as a consequence of HIV-1 infection. It is well recognized that opiate abuse
      exacerbates HIV-1 neuropathology, however, little is known about the role of
      complement proteins in opiate induced neuromodulation, specifically in the
      presence of co-morbidity such as HIV-1 infection. Complement levels are
      significantly increased in the HIV-1-infected brain, thus HIV-induced complement
      synthesis may represent an important mechanism for the pathogenesis of AIDS in
      the brain, but remains underexplored. Anti-HIV-1 antibodies are able to initiate
      complement activation in HIV-1 infected CNS cells such as microglia and
      astrocytes during the course of disease progression; however, this complement
      activation fails to clear and eradicate HIV-1 from infected cells. In addition,
      the antiretroviral agents used for HIV therapy cause dysregulation of lipid
      metabolism, endothelial, and adipocyte cell function, and activation of pro
      inflammatory cytokines. We speculate that both HIV-1 and opiates trigger a
      cytokine-mediated pro-inflammatory stimulus that modulates the complement cascade
      to exacerbate the virus-induced neurological damage. We examined the expression
      levels of C1q, SC5b-9, C5L2, C5aR, C3aR, and C9 key members of the complement
      cascade both in vivo in post mortem brain frontal cortex tissue from patients
      with HAND who used/did not use heroin, and in vitro using human microglial
      cultures treated with HIV tat and/or heroin. We observed significant expression
      of C1q and SC5b-9 by immunofluorescence staining in both the brain cortical and
      hippocampal region in HAND patients who abused heroin. Additionally, we observed
      increased gene expression of C5aR, C3aR, and C9 in the brain tissue of both HIV-1
      infected patients with HAND who abused and did not abuse heroin, as compared to
      HIV negative controls. Our results show a significant increase in the expression
      of complement proteins C9, C5L2, C5aR, and C3aR in HIV transfected microglia and
      an additional increase in the levels of these complement proteins in heroin
      treated HIV transfected microglia. This study highlights the a) potential roles
      of complement proteins in the pathogenesis of HIV-1-related neurodegenerative
      disorders; b) the combined effect of an opiate, like heroin, and HIV viral
      protein like HIV tat on complement proteins in normal human microglial cells and
      HIV transfected microglial cells. In the context of HAND, targeting selective
      steps in the complement cascade could help ameliorating the HIV burden in the
      CNS, thus investigations of complement-related therapeutic approaches for the
      treatment of HAND are warranted.

PMID- 29058549
TI  - Immunomodulatory activities of curcumin-stabilized silver nanoparticles: Efficacy
      as an antiretroviral therapeutic.
AB  - We synthesized and characterized curcumin-stabilized silver nanoparticles (Cur
      AgNP) and found them to be 45 nm by dynamic light scattering with a maximum
      absorbance at 406 nm. We evaluated Cur-AgNP for immunomodulatory activities and
      their potential as an antiretroviral agent. The antiretroviral effects of Cur
      AgNP were determined in ACH-2 cells latently infected with human immunodeficiency
      virus (HIV)-1. ACH-2 cells, 200,000/ml, were treated with Cur-AgNP for 24-48 h.
      Expression of HIV-1 LTR and p24, the pro-inflammatory cytokines, IL-1beta, TNF
      alpha, and NF-kappaB was quantitated. Treatment of ACH-2 cells latently infected
      with HIV-1 with Cur-AgNP produced no toxic effects but significantly inhibited
      the expression of HIV-1 LTR (-73%, P < 0.01) and p24 (-57%, P < 0.05), IL
      1betaalpha (-61%, P < 0.01), TNF-alphaalpha (-54%, P < 0.05), IL-6 (-68%, P <
      0.01), and NF-kappaB (-79%, P < 0.0001) as compared to untreated controls. Thus,
      Cur-AgNP have therapeutic potential as direct antiretroviral agents, as well as
      having immunomodulatory activities inhibiting the expression of pro-inflammatory
      mediators induced by infection with HIV-1. Experimental controls, such as
      curcumin alone, and conventional silver nanoparticles capped with citric acid,
      produced no similar biological effects. We conclude that treatment of HIV-1
      infected cells with Cur-AgNP significantly reduced replication of HIV by
      inhibition of NF-kappaB nuclear translocation and the downstream expression of
      the pro-inflammatory cytokines IL-1beta, TNF-alpha, and IL-6. Subsequent in vivo
      studies with Cur-AgNP using a humanized mouse model of HIV infection are
      underway.

PMID- 29058551
TI  - Aging in community and local NGOs: Empowering marginalized older women in South
      Korea.
AB  - This article is based on an embedded case study of selected older people's self
      help groups in urban South Korea, which aim to assist community-dwelling older
      adults, particularly poor and marginalized women, to age in their community and
      remain active and contributing members. The study highlights the importance of
      the role and capacity of nongovernmental organizations (NGOs) as partner
      organizations. Implications are important for other aging societies, particularly
      in Asia, where older women have been often confined by patriarchal oppression.

PMID- 29058552
TI  - Executive and nonexecutive demands of constructional measures within a children's
      psychiatric inpatient setting.
AB  - This study examined the role of executive functioning in constructional task
      performance (measured with the Rey Complex Figure Test-Copy Condition [RCFT] and
      Beery-Buktenica Developmental Test of Visual-Motor Integration [Beery-VMI])
      within a children's psychiatric inpatient setting. A chart review was conducted
      for 88 children (aged 6-12) who received a neuropsychological evaluation during a
      psychiatric inpatient hospitalization. Multiple regression analyses investigated
      the role of executive and nonexecutive demands on RCFT and Beery-VMI performance.
      Forty-three percent of the sample displayed a constructional weakness. Children
      with a constructional weakness had lower FSIQ scores and a higher rate of
      executive dysfunction. Performance on the RCFT was independently predicted by
      perceptual ability (i.e., Matrix Reasoning; p = .008; beta = .340) and
      attention/executive dysfunction (p = .003; beta = -.342; 9.4% of variance), while
      performance on the Beery-VMI was independently predicted by constructional
      ability (i.e., Block Design; p = .004, beta = .338). Results of this study
      demonstrate that the RCFT has greater executive demand than the VMI and yields a
      greater rate of impaired performance in an inpatient child sample as compared to
      the VMI. Clinical and research practices should consider the distinct differences
      between various constructional measures to ensure their proper use and
      interpretation with consideration to their varying executive and nonexecutive
      demands.

PMID- 29058553
TI  - Effects of body weight-support treadmill training on postural sway and gait
      independence in patients with chronic spinal cord injury.
AB  - OBJECTIVE: To examine the effects of a six-week body weight-support treadmill
      training (BWSTT) program on center-of-mass control and gait independence in
      chronic, incomplete spinal cord injury (iSCI) patients. DESIGN: Descriptive.
      SETTING: Clinica Los Coihues. Neurorehabilitation center in Santiago, Chile.
      PARTICIPANTS: 17 chronic iSCI patients and 17 healthy subjects. OUTCOME MEASURES:
      An instrumented sway (ISway) test was performed before and after the
      implementation of a six-week BWSTT program. The standing balance of participants
      was measured by Normalized jerk (NJ) and root mean square (RMS). These values
      were used to assess the standing balance of participants, and were correlated
      with the scores obtained on the Walking Index Spinal Cord Injury (WISCI) II test.
      RESULTS: Significant differences were found in standing balance (i.e., through
      NJ) after the BWSTT program (P = 0.016), but no significant differences were
      found in RMS values for postural sway (P = 0.693). None of the patients obtained
      improved WISCI II scores pre- vs. post-intervention. CONCLUSION: While a BWSTT
      program can improve center-of-mass control in iSCI patients, no effects were
      recorded for gait independence. TRIAL REGISTRATION: National Clinical Trials,
      registry number NCT02703883.

PMID- 29058554
TI  - Re: "Assessing the Detection of Middle East Respiratory Syndrome Coronavirus IgG
      in Suspected and Proven Cases of Middle East Respiratory Syndrome Coronavirus
      Infection" by Alhetheel et al. (Viral Immunol 2017;30:649-653.).

PMID- 29058556
TI  - Feasibility of a Miniature Esophageal Heat Exchange Device for Rapid Therapeutic
      Cooling in Newborns: Preliminary Investigations in a Piglet Model.
AB  - Therapeutic hypothermia (TH) after neonatal encephalopathy, commonly provided by
      72 hours of whole-body cooling using a wrap, limits parents' physical contact
      with their infants affecting bonding and may not be suitable for encephalopathic
      preterm infants with fragile skin. Alternative cooling methods are unavailable
      for this population. We investigated in a neonatal pig model the feasibility of
      achieving a 3.5 degrees C reduction in rectal temperature (Trectal) similar to
      clinical TH protocols from 38.5 degrees C (normothermia for pigs) to a target of
      35 degrees C +/- 0.2 degrees C, using a novel neonatal esophageal heat exchanger
      (NEHE), compared its efficacy to passive cooling, and investigated its ability to
      maintain target Trectal. Ventilated and anesthetized Landrace/Large white newborn
      pigs had the NEHE inserted. Water at adjustable temperatures and rates flowed
      down a central tube, returning up a surrounding distensible blind ending latex
      tube in a continuous loop. An initial experiment guided four subsequent cycles of
      passive cooling (30 minutes), rewarming to 38.5 degrees C, active esophageal
      cooling to 35 degrees C +/- 0.2 degrees C, active maintenance of target Trectal
      (30 minutes), and rewarming. We compared surface, rectal temperature, and
      hemodynamic changes among passive, active, and maintenance phases, and esophageal
      histopathology against control. Compared with passive cooling, esophageal cooling
      achieved target Trectal significantly earlier (71.3 minutes vs. 17.25 minutes, p
      = 0.003) with significantly greater rates of reduction in rectal (p = 0.0002) and
      surface (p = 0.005) temperatures and heart rate (p = 0.04). A water temperature
      of 39.1 degrees C-40.2 degrees C at a flow of 108-120 mL/min maintained Trectal
      around 35 degrees C +/- 0.2 degrees C. The higher peak heart rate and blood
      pressure within 8 minutes of the maintenance phase (p = 0.04) subsequently
      stabilized. Histopathology showed congestion, edema, and neutrophil infiltration
      with increasing cycles. Esophageal cooling is feasible and effective in achieving
      rapid cooling in newborns. Subsequent maintenance at this temperature required
      continued circulation of warm water. Esophageal histopathology needs further
      evaluation after 72 hours servo-control cooling with a narrower range of water
      temperatures in a larger group of animals.

PMID- 29058555
TI  - Auditory verbal habilitation is associated with improved outcome for children
      with cochlear implant.
AB  - OBJECTIVES: To study the impact of (re)habilitation strategy on speech-language
      outcomes for early, cochlear implanted children enrolled in different
      intervention programmes post implant. METHODS: Data relate to a total of 130
      children representing two pediatric cohorts consisting of 94 and 36 subjects,
      respectively. The two cohorts had different speech and language intervention
      following cochlear implantation, i.e. standard habilitation vs. auditory verbal
      (AV) intervention. Three tests of speech and language were applied covering
      language areas of receptive and productive vocabulary and language understanding.
      RESULTS: Children in AV intervention outperformed children in standard
      habilitation on all three tests of speech and language. When effect of
      intervention was adjusted with other covariates children in AV intervention still
      had higher odds at performing at age equivalent speech and language levels.
      CONCLUSION: Compared to standard intervention, AV intervention is associated with
      improved outcome for children with CI. Based on this finding, we recommend that
      all children with HI should be offered this intervention and it is, therefore,
      highly relevant when National boards of Health and Social Affairs recommend
      basing the habilitation on principles from AV practice. It should be noted, that
      a minority of children use spoken language with sign support. For this group it
      is, however, still important that educational services provide auditory skills
      training.

PMID- 29058557
TI  - Epidemiology of traumatic spinal cord injury in childhood and adolescence in
      Galicia, Spain: report of the last 26-years.
AB  - OBJECTIVE: To analyze the characteristics of traumatic spinal cord injury in
      children of Galicia (Spain). DESIGN: Descriptive and retrospective study.
      METHODS: Data extracted from the internal registry of the Spinal Cord Injury Unit
      and the patient's medical records, between March 1988 and December 2014.
      INCLUSION CRITERIA: patients aged <= 17 years with a traumatic spinal cord
      injury. OUTCOME MEASURES: Total patients, percentages, incidence, ASIA scale
      results and improvement. RESULTS: A total of 68 patients were included. The
      incidence was 5.6 cases/1,000,000 inhabitants/year. The mean age was 14.4 years
      (median: 16). Only 25% were younger than 15. Male patients accounted for 73.5% of
      the total. The main cause were traffic accidents (60.3%; n = 41), being higher
      (77.8%) in children <= 10 years. Other etiologies included falls (19.1%), diving
      accidents (16.2%) and other causes (4.4%). Eleven patients (16.2%) had injuries
      classified as SCIWORA, 8 (72.7%) of them aged <= 10 years. The mean age of the
      SCIWORA group was 7.5 years versus 15.7 years in the non-SCIWORA group (P <
      0.001). Half (50%) of these patients had a complete spinal cord injury and, of
      these, 64.6% were paraplegic. CONCLUSIONS: Traumatic spinal cord injuries are
      rare in children, and most cases occur between 15 and 17 years. Unlike in adults,
      SCIs in children mostly involve the thoracic spine. Most patients aged <= 10
      years have SCIWORA. The most common etiology continues to be traffic accidents,
      although sports accidents prevail among adolescent patients.

PMID- 29058558
TI  - Solution-Focused Coaching in Pediatric Rehabilitation: Investigating
      Transformative Experiences and Outcomes for Families.
AB  - AIMS: A qualitative study was conducted to investigate family experiences and
      outcomes of Solution-Focused Coaching in pediatric rehabilitation (SFC-peds).
      METHODS: Two interviews (5 months apart) were conducted with nine sets of family
      members who had received SFC-peds, within the past 6 months, from therapists with
      3-10 years of experience using the approach. Transcripts were analyzed using
      thematic analysis and a phenomenological approach. RESULTS: Participants
      experienced a goal-oriented collaborative process, high engagement, enhanced
      capacity and community participation, and empowered mindsets. The therapy process
      was seen as a collaborative solution-focused conversation, situated in the
      client's world, and involving individualized and co-created goals and plans. SFC
      peds provided families with a supportive, structured, and paced goal-setting
      process. Reported enhancements to capacity included child/youth skill
      development, enhanced parent skills, enhanced parent knowledge of their child and
      options, and changes in parenting. Increased community participation was also
      reported. Empowered mindsets involved increased confidence, increased self
      efficacy and self-determination, and broadened perspectives and expectations.
      CONCLUSIONS: The study provides evidence for the utility of SFC-peds and the
      importance of engaging families in a goal-oriented collaborative process.
      Implications concern greater understanding of transactional dynamics in therapy
      and real-world client change, and the need to develop measures of client/family
      resiliency.

PMID- 29058559
TI  - Evaluation of an active rehabilitation program for concussion management in
      children and adolescents.
AB  - OBJECTIVE: To estimate the extent to which post-concussion symptoms were
      influenced by participation in an Active Rehabilitation (AR) program (aerobic
      exercise, coordination drills, visualization and education) for children and
      adolescents who are slow to recover from concussion. A secondary exploratory
      objective included examining the influence of sex on symptom evolution. METHODS:
      Analysis of prospectively collected data was performed on 277 youth who initiated
      an AR program, between three and four weeks post-injury at a Concussion Clinic in
      a tertiary care paediatric teaching hospital. MAIN OUTCOME MEASURE: Post
      concussion symptom scale (PCSS) from Sport Concussion Assessment Tool-3 (SCAT 3).
      RESULTS: Children and adolescents participating in an active rehabilitation
      program displayed improved post-concussion symptom severity at follow-up (median
      = 9.5) compared to pre-intervention (median = 18) (p < .05). Patients
      demonstrated improved physical, cognitive, emotional and sleep-related post
      concussion symptoms (p < .05). Female sex was associated with an increased post
      concussion symptom severity at follow-up. CONCLUSIONS: Youth experiencing
      persisting symptoms three to four weeks post-concussion demonstrated improved
      post-concussion symptoms scores (physical, cognitive, emotional and sleep
      related) with participation in an active rehabilitation program.

PMID- 29058560
TI  - Vancomycin-Resistant Enterococci: A Review of Antimicrobial Resistance Mechanisms
      and Perspectives of Human and Animal Health.
AB  - Vancomycin-resistant enterococci (VRE) are both of medical and public health
      importance associated with serious multidrug-resistant infections and persistent
      colonization. Enterococci are opportunistic environmental inhabitants with a
      remarkable adaptive capacity to evolve and transmit antimicrobial-resistant
      determinants. The VRE gene operons show distinct genetic variability and
      apparently continued evolution leading to a variety of antimicrobial resistance
      phenotypes and various environmental and livestock reservoirs for the most common
      van genes. Such complex diversity renders a number of important therapeutic
      options including "last resort antibiotics" ineffective and poses a particular
      challenge for clinical management. Enterococci resistance to glycopeptides and
      multidrug resistance warrants attention and continuous monitoring.

PMID- 29058561
TI  - Implementing a multi-sectoral response to HIV: a case study of AIDS councils in
      the Mpumalanga Province, South Africa.
AB  - BACKGROUND: A multi-sectoral response is advocated by international organisations
      as a good strategy to address the multiple drivers and impact of human
      immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and was
      historically mandated as a condition of funding. In March 2017, the South African
      National AIDS Council (SANAC) launched the latest 5 year National Strategic Plan
      (NSP) to address HIV, sexually transmitted infections and tuberculosis. As with
      previous iterations, the NSP calls for multi-sectoral action (MSA) and mandates
      AIDS councils (ACs) at different levels to coordinate its implementation. Efforts
      have been made to advocate for the adoption of MSA in South Africa, yet
      evaluation of these efforts is currently limited. OBJECTIVE: This paper assesses
      the implementation of a multi-sectoral response to HIV in South Africa, through a
      case study of the Mpumalanga Province. METHODS: We identified and reviewed key
      policy documents, conducted 12 interviews and held six focus group discussions.
      We also drew on our involvement, through participant observation, in the
      development of NSPs and in AC meetings. RESULTS: SANAC is struggling to provide
      much-needed support to provincial, district and local ACs. Therefore, most ACs
      are generally weak and failing to implement MSA. Membership is voluntary, there
      is a lack of sustained commitment and they do not include representatives from
      all sectors. There is little capacity to undertake the activities necessary for
      coordinating the implementation of MSA, and unclear roles and responsibilities
      within ACs result in divisions and tension between sectors. There is inadequate
      senior political leadership and funding to facilitate effective implementation of
      MSA. CONCLUSION: We identified three interventions that we argue are required to
      support the effective implementation of MSA: strengthening and stabilising the
      SANAC structure; building capacity of ACs; and creating an enabling environment
      for effective implementation of MSA through political leadership, support and
      resourcing of the HIV response.

PMID- 29058562
TI  - Does L-Tryptophan supplementation reduce chewing deficits in an experimental
      model of cerebral palsy?
AB  - Children with cerebral palsy commonly present with feeding difficulties that
      result from multiple orofacial sequelae, especially deficits in mastication. A
      previous study demonstrated that perinatal protein undernutrition accentuated the
      chewing impact in an experimental model of cerebral palsy. Therefore, the present
      study investigated whether nutritional manipulation reversed or minimized the
      chewing sequelae in cerebral palsy. We emphasized the relevance of evaluating the
      therapeutic potential of nutrients, especially tryptophan supplementation, to
      reduce the chewing deficits that are typical of this syndrome. Clarification of
      the role of nutrients may help in the development of new treatment strategies for
      these children.

PMID- 29058563
TI  - Osmotic Concentration of Zebrafish (Danio rerio) Body Fluids Is Lower in Larvae
      than in Adults.
AB  - We intended to perform optical and structural measurements on larval zebrafish
      eyes at 5 days post fertilization, that is, the earliest age at which zebrafish
      show visually guided behavior. However, excised larval crystalline lenses
      deteriorated quickly if immersed in a medium that gives good results with adult
      lenses from a variety of fish species. We suspected that the larvae have body
      fluids of lower osmolality and tested a medium with 240 mOsm, which is 75% of the
      established adult value of 320 mOsm. The optical quality of freshly excised and
      immersed lenses was used to judge the osmotic matches. In addition, we tested how
      well the shape of the eye is preserved in fixatives of different osmolalities. In
      both cases, 240 mOsm produced the best results. Immersed lenses performed better
      and the fixed eyes had a more natural shape. Our findings indicate that zebrafish
      body fluids have lower osmolality in larvae than in adults. This is probably due
      to an unfavorable body surface-to-volume ratio and incompletely developed
      regulatory mechanisms. Body fluid osmolality deviating from the adult value has
      to be taken into account in optical and histological work.

PMID- 29058564
TI  - Developing standards for an integrated approach to workplace facilitation for
      interprofessional teams in health and social care contexts: a Delphi study.
AB  - Integration of health and social care forms part of health and social care policy
      in many countries worldwide in response to changing health and social care needs.
      The World Health Organization's appeal for systems to manage the global
      epidemiologic transition advocates for provision of care that crosses boundaries
      between primary, community, hospital, and social care. However, the focus on
      structural and process changes has not yielded the full benefit of expected
      advances in care delivery. Facilitating practice in the workplace is a widely
      recognised cornerstone for developments in the delivery of health and social care
      as collaborative and inclusive relationships enable frontline staff to develop
      effective workplace cultures that influence whether transformational change is
      achieved and maintained. Workplace facilitation embraces a number of different
      purposes which may not independently lead to better quality of care or improved
      patient outcomes. Holistic workplace facilitation of learning, development, and
      improvement supports the integration remit across health and social care systems
      and avoids duplication of effort and waste of valuable resources. To date, no
      standards to guide the quality and effectiveness of integrated facilitation have
      been published. This study aimed to identify key elements constitute standards
      for an integrated approach to facilitating work-based learning, development,
      improvement, inquiry, knowledge translation, and innovation in health and social
      care contexts using a three rounds Delphi survey of facilitation experts from 10
      countries. Consensus about priority elements was determined in the final round,
      following an iteration process that involved modifications to validate content.
      The findings helped to identify key qualities and skills facilitators need to
      support interprofessional teams to flourish and optimise performance. Further
      research could evaluate the impact of skilled integrated facilitation on health
      and social care outcomes and the well-being of frontline interprofessional teams.

PMID- 29058565
TI  - Twelve tips for using clinical cases to teach medical ethics.
AB  - The essential role of clinical case discussions in the teaching of medical ethics
      is well recognized. Based upon published literature and the authors' curricular
      development experience, the following 12 tips cover all major aspects of the case
      method for teaching clinical ethics and offer practical suggestions for designing
      and conducting case discussions.

PMID- 29058566
TI  - Effect of sterilisation and storage conditions on the migration of bisphenol A
      from tinplate cans of the Lebanese market.
AB  - The use of bisphenol A (BPA) in lacquer coating of food cans has been restricted
      by different authorities in many countries, such as in Europe. However, such
      regulation does not exist in many other countries including Lebanon. Due to the
      lack of data on the quality of Lebanese can production; this study investigates
      the migration of BPA from two types of tinplate cans manufactured in Lebanon,
      before and after sterilisation. Cans were analysed under different storage
      conditions (time and temperature) and filled with an aqueous simulant. The
      determination of BPA was carried out using UPLC with fluorescence detection, and
      further confirmed by MS detection. After sterilisation BPA levels drastically
      increased from an average of 0.15 to 109 ug/kg, giving a BPA migration around
      10.5 ug/dm2 for both types of cans. Storage temperature and time had no
      significant influence on BPA levels in sterilised cans (p-value > 0.05); however,
      these factors significantly affected BPA levels in non-sterilised cans.

PMID- 29058567
TI  - An interprofessional objective structured teaching experience (iOSTE): An
      interprofessional preceptor professional development activity.
AB  - There has been a recent shift to develop and implement interprofessional
      education for learners during their "clinical" years. With this shift comes a
      specific need to develop preceptors in the area of interprofessional precepting.
      The interprofessional objective structured teaching experience (iOSTE) is one
      method for developing preceptors. The iOSTE was developed from experience with an
      interprofessional teaching clinic. Full and short versions of the iOSTE were
      implemented across multiple universities. The iOSTE gives preceptors an
      opportunity to gain experience with key skills associated with precepting
      interprofessional learners in clinical settings. Participants evaluated the iOSTE
      after the session using Likert scale ratings and open-ended questions.
      Descriptive statistics, independent samples T-tests, and content analysis were
      used to analyse the data. A total of 96 individuals from 15 different professions
      and three different universities participated in the iOSTE, with 59.4% (n = 57)
      completing the iOSTE evaluation. The iOSTE was highly rated with significant
      differences between the full and short versions of the iOSTE for three evaluation
      items. Content analysis revealed common themes that preceptors took away from the
      experience were of "all voices included" and "interprofessional precepting
      skills". Overall, the iOSTE appears to a feasible and effective method for
      developing interprofessional preceptors.

PMID- 29058568
TI  - Retention and use of newborn resuscitation skills following a series of helping
      babies breathe trainings for midwives in rural Ghana.
AB  - BACKGROUND: The Helping Babies Breathe (HBB) program teaches basic newborn
      resuscitation techniques to birth attendants in low-resource settings. Previous
      studies have demonstrated a decrease in mortality following training, mostly in
      large hospitals. However, low-volume clinics in rural regions with no physician
      immediately available likely experience a greater relative burden of newborn
      mortality. This study aimed to determine the impact of HBB trainings provided to
      rural Ghanaian midwives on their skills retention and on first 24 hour mortality
      of the newborns they serve. METHODS: American Acadamy of Paediatrics (AAP)
      trained Master Trainers conducted two 2-day HBB trainings and 2-day refresher
      courses one year later for 48 midwives from Ghanaian rural health clinics.
      Trainee skills were evaluated by Objective Structured Clinical Examination (OSCE)
      at three time points: immediately after training, four months after training, and
      four months after the refresher. Midwives recorded the single highest level of
      resuscitation performed on each newborn delivered for one year. RESULTS: 48
      midwives attended the two trainings, 32 recorded data from 2,383 deliveries, and
      13 completed OSCE simulations at all three time points. The midwives' OSCE scores
      decreased from immediately after training (94.9%) to four months later (81.2%, p
      < 0.00001). However, four months following the refresher course, scores improved
      to the same high level attained initially (92.7%, p = 0.0013). 5.0% of neonates
      required bag-mask ventilation and 0.71% did not survive, compared with a
      nationwide first 24 hour mortality estimate of 1.7%. CONCLUSIONS: The midwives'
      performance on the simulation exercise indicates that an in-depth refresher
      course provided one year after the initial training likely slows the decay in
      skills that occurs after initial training. Our finding that 5.0% of newborns
      required bag-mask ventilation is consistent with global estimates. Our observed
      first 24 hour mortality rate of 0.71% is lower than nationwide estimates,
      indicating the training likely prevented deaths due to birth asphyxia.

PMID- 29058569
TI  - Surgical Site Infections after Appendectomy Performed in Low and Middle Human
      Development-Index Countries: A Systematic Review.
AB  - BACKGROUND: Acute appendicitis is a common surgical emergency worldwide. Early
      intervention is associated with better outcomes. In low and middle Human
      Development-Index Countries (LMHDICs), late presentation and poor access to
      healthcare facilities can contribute to greater illness severity and higher
      complication rates, such as post-operative surgical site infections (SSIs). The
      current rate of SSIs post-appendectomy in low- and middle-index settings has yet
      to be described. METHODS: We performed a systemic review of the literature
      describing the incidence and management of SSIs after appendectomy in LMHDICs. We
      conducted qualitative and quantitative analysis of the data in manuscripts
      describing patients undergoing appendectomy to establish a baseline SSI rate for
      this procedure in these settings. RESULTS: Four hundred twenty-three abstracts
      were initially identified. Of these, 35 studies met the criteria for qualitative
      and quantitative analysis. The overall weighted, pooled SSI rated were 17.9
      infections/100 open appendectomies (95% confidence interval [CI] 10.4-25.3
      infections/100 open appendectomies) and 8.8 infections/100 laparoscopic
      appendectomies (95% CI 4.5-13.2 infections/100 laparoscopic appendectomies). The
      SSI rates were higher in complicated appendicitis and when pre-operative
      antibiotic use was not specified. CONCLUSIONS: Observed SSI rates after
      appendectomy in LMHDICs are dramatically higher than rates in high Human
      Development-Index Countries. This is particularly true in cases of open
      appendectomy, which remains the most common surgical approach in LMHDICs. These
      findings highlight the need for SSI prevention in LMHDICs, including prompt
      access to medical and surgical care, routine pre-operative antibiotic use, and
      implementation of bundled care packages and checklists.

PMID- 29058570
TI  - Occupational noise exposure and hearing defects among sawmill workers in the
      south of Thailand.
AB  - The aim of this study was to investigate occupational noise exposure and hearing
      defects among sawmill workers in the south of Thailand. Seven hundred sawmill
      workers participated, of which 335 (47.9%) were male. The mean age of the sawmill
      workers was 33.5 years (SD 10.2), and more than 60% were <35 years old; 75.1% of
      the workers had less than 5 years of work experience. Only about one in four
      workers (25%) had been trained in use of personal protective equipment (PPE), and
      half of the participants never or rarely wore PPE while working. The prevalence
      rate of noise-induced hearing loss (NIHL) was 22.8% (N = 42). Male workers had
      significantly higher risk than female workers (odds ratio [OR] = 2.21). Workers
      aged older than 25 years had significantly higher risks for NIHL (OR = 3.51
      12.42) than workers younger than 25 years. Sawing workers had higher risk for
      NIHL than office workers (OR = 3.07).

PMID- 29058571
TI  - The Moral Inadequacy of Cremation.
AB  - Cremation has substantial practical benefits. Not only is it much cheaper than
      traditional burial, but it also comes without its ecological burden. Despite
      this, we argue that cremation is an inadequate way of disposing of the dead
      because it entails the destruction of community memory, and, by extension,
      community and individual identity. It deprives the living of these benefits,
      while also treating the dead in way which goes against common intuitions about
      personhood, anthropology and respect for the will of the deceased. Death is
      perhaps one of the most important subjects in philosophy, and by marginalising it
      through cremation and related practices, we deprive ourselves of its didactic and
      social uses. The case we make against cremation is not absolute, but we hope it
      succeeds in casting doubt on the presumed neutrality of cremation. Our essay is
      under three heads: (1) we consider the practical benefits of cremation; (2) we
      reconsider the value of cremation in light of what it deprives individuals and
      communities of and; (3) we analyse the significance of the corpse in regard to
      cremation.

PMID- 29058574
TI  - Second Chances: Accepting a Dismissed Patient Back Into Your Practice.

PMID- 29058575
TI  - Impact of Immigration on Prenatal Care Use and Birth Weight: Evidence from
      California in the 1990's.

PMID- 29058572
TI  - Lifetime marijuana and alcohol use, and cognitive dysfunction in people with
      human immunodeficiency virus infection.
AB  - BACKGROUND: Substance use is common among people with human immunodeficiency
      virus (HIV) infection. Alcohol, marijuana, and HIV can have negative effects on
      cognition. Associations between current and lifetime marijuana and alcohol use
      and cognitive dysfunction in people with HIV infection were examined. METHODS:
      Some 215 HIV-infected adults with Diagnostic and Statistical Manual of Mental
      Disorders Fourth Edition (DSM-IV) substance dependence or ever injection drug use
      were studied. In adjusted cross-sectional regression analyses associations were
      assessed between current marijuana use, current heavy alcohol use, lifetime
      marijuana use, lifetime alcohol use, duration of heavy alcohol use (the
      independent variables), and 3 measures of cognitive dysfunction (dependent
      variables): both the (i) memory and (ii) attention domains from the Montreal
      Cognitive Assessment (MoCA) and the (iii) 4-item cognitive function scale (CF4)
      from the Medical Outcomes Study HIV Health Survey (MOS-HIV). Analyses were
      adjusted for demographics, primary language, depressive symptoms, anxiety,
      comorbidities, antiretroviral therapy, hepatitis C virus (ever), duration of HIV
      infection (years), HIV-viral load (log copies/mL), CD4 cell count, lifetime and
      recent cocaine use, and recent illicit and prescribed opioid use. RESULTS:
      Current marijuana use was significantly and negatively associated with the MOS
      HIV CF4 score (adjusted mean difference = -0.40, P = .01). Current marijuana use
      was not significantly associated with either MoCA score. Lifetime marijuana use
      and current heavy and lifetime alcohol use and duration of heavy alcohol use were
      not associated with any measure of cognitive dysfunction. CONCLUSION: Current
      marijuana use was associated with one measure of cognitive dysfunction, but there
      was not a consistent pattern of association with lifetime marijuana use or
      alcohol use and measures of cognitive dysfunction. Understanding the mechanism by
      which marijuana, with and without alcohol, are associated with worse cognition
      warrants larger, longer studies with more precise and diverse measurements of
      cognitive function.

PMID- 29058576
TI  - LCS-TA to identify similar fragments in RNA 3D structures.
AB  - BACKGROUND: In modern structural bioinformatics, comparison of molecular
      structures aimed to identify and assess similarities and differences between them
      is one of the most commonly performed procedures. It gives the basis for
      evaluation of in silico predicted models. It constitutes the preliminary step in
      searching for structural motifs. In particular, it supports tracing the molecular
      evolution. Faced with an ever-increasing amount of available structural data,
      researchers need a range of methods enabling comparative analysis of the
      structures from either global or local perspective. RESULTS: Herein, we present a
      new, superposition-independent method which processes pairs of RNA 3D structures
      to identify their local similarities. The similarity is considered in the context
      of structure bending and bonds' rotation which are described by torsion angles.
      In the analyzed RNA structures, the method finds the longest continuous segments
      that show similar torsion within a user-defined threshold. The length of the
      segment is provided as local similarity measure. The method has been implemented
      as LCS-TA algorithm (Longest Continuous Segments in Torsion Angle space) and is
      incorporated into our MCQ4Structures application, freely available for download
      from http://www.cs.put.poznan.pl/tzok/mcq/ . CONCLUSIONS: The presented approach
      ties torsion-angle-based method of structure analysis with the idea of local
      similarity identification by handling continuous 3D structure segments. The first
      method, implemented in MCQ4Structures, has been successfully utilized in RNA
      Puzzles initiative. The second one, originally applied in Euclidean space, is a
      component of LGA (Local-Global Alignment) algorithm commonly used in assessing
      protein models submitted to CASP. This unique combination of concepts implemented
      in LCS-TA provides a new perspective on structure quality assessment in local and
      quantitative aspect. A series of computational experiments show the first results
      of applying our method to comparison of RNA 3D models. LCS-TA can be used for
      identifying strengths and weaknesses in the prediction of RNA tertiary
      structures.

PMID- 29058579
TI  - Breach Management Flowchart.

PMID- 29058578
TI  - Temporal dynamic of malaria in a suburban area along the Niger River.
AB  - BACKGROUND: Even if rainfall and temperature are factors classically associated
      to malaria, little is known about other meteorological factors, their variability
      and combinations related to malaria, in association with river height variations.
      Furthermore, in suburban area, urbanization and growing population density should
      be assessed in relation to these environmental factors. The aim of this study was
      to assess the impact of combined environmental, meteorological and hydrological
      factors on malaria incidence through time in the context of urbanization.
      METHODS: Population observational data were prospectively collected. Clinical
      malaria was defined as the presence of parasites in addition to clinical
      symptoms. Meteorological and hydrological factors were measured daily. For each
      factors variation indices were estimated. Urbanization was yearly estimated
      assessing satellite imaging and field investigations. Principal component
      analysis was used for dimension reduction and factors combination. Lags between
      malaria incidences and the main components were assessed by cross-correlation
      functions. Generalized additive model was used to assess relative impact of
      different environmental components, taking into account lags, and modelling non
      linear relationships. Change-point analysis was used to determine transmission
      periods within years. RESULTS: Malaria incidences were dominated by annual
      periodicity and varied through time without modification of the dynamic, with no
      impact of the urbanization. The main meteorological factor associated with
      malaria was a combination of evaporation, humidity and rainfall, with a lag of 3
      months. The relationship between combined temperature factors showed a linear
      impact until reaching high temperatures limiting malaria incidence, with a lag
      3.25 months. Height and variation of the river were related to malaria incidence
      (respectively 6 week lag and no lag). CONCLUSIONS: The study emphasizes no
      decreasing trend of malaria incidence despite accurate access to care and control
      strategies in accordance to international recommendations. Furthermore, no
      decreasing trend was showed despite the urbanization of the area. Malaria
      transmission remain increase 3 months after the beginning of the dry season.
      Addition to evaporation versus humidity/rainfall, nonlinear relationship for
      temperature and river height and variations have to be taken into account when
      implementing malaria control programmes.

PMID- 29058577
TI  - Knowledge, attitudes, and practices of pediatricians on infantile colic in the
      Middle East and North Africa region.
AB  - BACKGROUND: Regional evidence-based guidelines for the prophylaxis and management
      of infantile colic are not available for the Middle East and North Africa (MENA)
      region. The Allied Against Infantile Functional GI Disorders (ACT) Working Group
      was created in January, 2015 to determine the knowledge gaps and the current
      management practices of infantile colic by physicians in the MENA region. The ACT
      group determined the need for a survey to address these questions. The objectives
      of the survey were to highlight current clinical practices on the management of
      infantile colic and to raise awareness on colic severity in the MENA region.
      METHODS: The ACT working group developed the survey which included respondent
      characteristics and closed questions on practice in colic prevention. The survey
      was subject to validation and ethics committee approval in all countries.
      RESULTS: A total of 1628 physicians (mostly pediatricians (75.4%), neonatologists
      (2.4%) and general practitioners (19.8%)) responded to the survey. The 5 most
      represented countries were KSA (27.9%), Kuwait (22.1%), Morocco (13.8%), Lebanon
      (10.6%), and Iraq (7.4%). Most of the respondents (77.8%) practiced in
      governmental settings. A majority of respondents (91.7%) reported that colic is
      diagnosed predominantly by clinical examination. Above 63%, of pediatricians
      surveyed, believed that the colic prevalence rate was >40%, which is greater than
      the 20% rate reported in worldwide surveys. Yet, most of the responding
      physicians (73%) prefer to simply reassure parents rather than prescribe a
      therapeutic agent. Most physicians were either neutral (58%) or did not endorse
      (18.4%) colic prophylaxis. Of those who prescribed formulae for non-breastfed
      children, a majority (64.3%) chose "Comfort" formulae over hydrolyzed or lactose
      free formulae or formulae with probiotics. CONCLUSIONS: The results of this
      survey suggest that a substantial proportion of responding physicians from the
      selected MENA countries do not advocate for prophylaxis of colic. The findings of
      this survey suggest that more educational efforts are required to increase
      awareness of the strong body of evidence supporting the efficacy of probiotics in
      the prevention and management of infantile colic.

PMID- 29058580
TI  - Sleeping with the enemy: Clostridium difficile infection in the intensive care
      unit.
AB  - Over the last years, there was an increase in the number and severity of
      Clostridium difficile infections (CDI) in all medical settings, including the
      intensive care unit (ICU). The current prevalence of CDI among ICU patients is
      estimated at 0.4-4% and has severe impact on morbidity and mortality. An
      estimated 10-20% of patients are colonized with C. difficile without showing
      signs of infection and spores can be found throughout ICUs. It is not yet
      possible to predict whether and when colonization will become infection.
      Figuratively speaking, our patients are sleeping with the enemy and we do not
      know when this enemy awakens.Most patients developing CDI in the ICU show a mild
      to moderate disease course. Nevertheless, difficult-to-treat severe and
      complicated cases also occur. Treatment failure is particularly frequent in ICU
      patients due to comorbidities and the necessity of continued antibiotic
      treatment. This review will give an overview of current diagnostic, therapeutic,
      and prophylactic challenges and options with a special focus on the ICU
      patient.First, we focus on diagnosis and prognosis of disease severity. This
      includes inconsistencies in the definition of disease severity as well as
      diagnostic problems. Proceeding from there, we discuss that while at first glance
      the choice of first-line treatment for CDI in the ICU is a simple matter guided
      by international guidelines, there are a number of specific problems and
      inconsistencies. We cover treatment in severe CDI, the problem of early
      recognition of treatment failure, and possible concepts of intensifying
      treatment. In conclusion, we mention methods for CDI prevention in the ICU.

PMID- 29058581
TI  - Opsoclonus myoclonus syndrome in a patient with Japanese encephalitis: a case
      report.
AB  - BACKGROUND: Opsoclonus myoclonus syndrome is a rare neurological disorder that
      usually manifests as a paraneoplastic phenomenon. Although some viruses are
      reported to cause this condition, opsoclonus myoclonus syndrome by Japanese
      encephalitis has not been reported previously. CASE PRESENTATION: Here we present
      the case of a 31-year-old Sri Lankan woman who presented with fever, altered
      level of consciousness, opsoclonus, and facial myoclonus. She was diagnosed as
      having Japanese encephalitis based on cerebrospinal fluid and serum Japanese
      encephalitis-specific immunoglobulin M antibody and characteristic magnetic
      resonance imaging abnormalities. She was given intravenously administered
      methylprednisolone pulses (1000 mg per day) for 5 days. With this she improved
      gradually with reduction in opsoclonus and myoclonic movements. Her limb muscle
      power and speech also improved slowly. CONCLUSIONS: We intended to highlight the
      fact that opsoclonus myoclonus syndrome can be a feature of infection with
      Japanese encephalitis and that it can be added to the list of viruses which cause
      opsoclonus. Currently there is no well-accepted treatment for opsoclonus
      myoclonus syndrome and intravenously administered methylprednisolone pulses and
      immunosuppressants can be used successfully in these patients for early recovery.

PMID- 29058582
TI  - An Arabidopsis introgression zone studied at high spatio-temporal resolution:
      interglacial and multiple genetic contact exemplified using whole nuclear and
      plastid genomes.
AB  - BACKGROUND: Gene flow between species, across ploidal levels, and even between
      evolutionary lineages is a common phenomenon in the genus Arabidopsis. However,
      apart from two genetically fully stabilized allotetraploid species that have been
      investigated in detail, the extent and temporal dynamics of hybridization are not
      well understood. An introgression zone, with tetraploid A. arenosa introgressing
      into A. lyrata subsp. petraea in the Eastern Austrian Forealps and subsequent
      expansion towards pannonical lowlands, was described previously based on
      morphological observations as well as molecular data using microsatellite and
      plastid DNA markers. Here we investigate the spatio-temporal context of this
      suture zone, making use of the potential of next-generation sequencing and whole
      genome data. By utilizing a combination of nuclear and plastid genomic data, the
      extent, direction and temporal dynamics of gene flow are elucidated in detail and
      Late Pleistocene evolutionary processes are resolved. RESULTS: Analysis of
      nuclear genomic data significantly recognizes the clinal structure of the
      introgression zone, but also reveals that hybridization and introgression is more
      common and substantial than previously thought. Also tetraploid A. lyrata and A.
      arenosa subsp. borbasii from outside the previously defined suture zone show
      genomic signals of past introgression. A. lyrata is shown to serve usually as the
      maternal parent in these hybridizations, but one exception is identified from
      plastome-based phylogenetic reconstruction. Using plastid phylogenomics with
      secondary time calibration, the origin of A. lyrata and A. arenosa lineages is
      pre-dating the last three glaciation complexes (approx. 550,000 years ago).
      Hybridization and introgression followed during the last two glacial-interglacial
      periods (since approx. 300,000 years ago) with later secondary contact at the
      northern and southern border of the introgression zone during the Holocene.
      CONCLUSIONS: Footprints of adaptive introgression in the Northeastern Forealps
      are older than expected and predate the Last Glaciation Maximum. This correlates
      well with high genetic diversity found within areas that served as refuge area
      multiple times. Our data also provide some first hints that early introgressed
      and presumably preadapted populations account for successful and rapid
      postglacial re-colonization and range expansion.

PMID- 29058583
TI  - IL-17 signalling restructures the nasal microbiome and drives dynamic changes
      following Streptococcus pneumoniae colonization.
AB  - BACKGROUND: The bacterial pathogen Streptococcus pneumoniae colonizes the
      nasopharynx prior to causing disease, necessitating successful competition with
      the resident microflora. Cytokines of the IL-17 family are important in host
      defence against this pathogen but their effect on the nasopharyngeal microbiome
      is unknown. Here we analyse the influence of IL-17 on the composition and
      interactions of the nasopharyngeal microbiome before and after pneumococcal
      colonization. RESULTS: Using a murine model and 16S rRNA profiling, we found that
      a lack of IL-17 signalling led to profound alterations in the nasal but not lung
      microbiome characterized by decreased diversity and richness, increases in
      Proteobacteria and reduction in Bacteroidetes, Actinobacteria and Acidobacteria.
      Following experimental pneumococcal nasal inoculation, animals lacking IL-17
      family signalling showed increased pneumococcal colonization, though both wild
      type and knockout animals showed as significant disruption of nasal microbiome
      composition, with increases in the proportion of Proteobacteria, even in animals
      that did not have persistent colonization. Sparse correlation analysis of the
      composition of the microbiome at various time points after infection showed
      strong positive interactions within the Firmicutes and Proteobacteria, but strong
      antagonism between members of these two phyla. CONCLUSIONS: These results show
      the powerful influence of IL-17 signalling on the composition of the nasal
      microbiome before and after pneumococcal colonization, and apparent lack of
      interspecific competition between pneumococci and other Firmicutes. IL-17 driven
      changes in nasal microbiome composition may thus be an important factor in
      successful resistance to pneumococcal colonization and potentially could be
      manipulated to augment host defence against this pathogen.

PMID- 29058584
TI  - Radiographic characteristics in congenital scoliosis associated with split cord
      malformation: a retrospective study of 266 surgical cases.
AB  - BACKGROUND: Vertebrae, ribs, and spinal cord are anatomically adjacent
      structures, and their close relationships are clinically important for planning
      better corrective surgical approach. The objective is to identify the
      radiographic characteristics in surgical patients with congenital scoliosis (CS)
      and coexisting split cord malformation (SCM). METHODS: A total of 266 patients
      with CS and SCM underwent surgical treatment at our hospital between May 2000 and
      December 2015 was retrospectively identified. The demographic distribution and
      radiographic data were collected to investigate the characteristics of spine
      curve, vertebral, rib, and intraspinal anomalies. According to Pang's
      classification, all patients were divided into two groups: type I group is
      defined as two hemicords, each within a separate dural tube separated by a bony
      or cartilaginous medial spur, while type II group is defined as two hemicords
      within a single dural tube separated by a nonrigid fibrous septum. RESULTS: There
      were 104 patients (39.1%) in Type I group and 162 patients (60.9%) in Type II
      group. SCM was most commonly found in the lower thoracic and lumbar regions. The
      mean length of the septum in Type I SCM was significantly shorter than Type II
      SCM (2.7 vs. 5.2 segments). Patients in Type I group had a higher proportion of
      kyphotic deformity (22.1%). The vertebral deformities were simple in only 16.5%
      and multiple in 83.5% of 266 cases. Patients in Type I group presented higher
      prevalence of multiple (90.4%) and extensive (5.1 segments) malformation of
      vertebrae. In addition, hypertrophic lamina and bulbous spinous processes were
      more frequent in Type I group (29.7%), even developing into the "volcano-shape"
      deformities. Rib anomalies occurred in 62.8% of all patients and 46.1% of them
      were complex anomalies. The overall prevalence of other intraspinal anomalies was
      42.9%. The most common coexisting intraspinal anomalies was syringomyelia
      (30.5%). CONCLUSION: The current study, with the largest cohort to date,
      demonstrated that patients with CS and coexisting SCM presented high prevalence
      of multiple vertebral deformities, rib and intraspinal anomalies. The length of
      the split segment in Type I SCM was shorter than that in Type II SCM. Compared
      with Type II SCM, patients with Type I SCM presented with higher incidence of
      kyphotic deformity, more extensive and complicated vertebral anomalies, and more
      complex rib anomalies.

PMID- 29058586
TI  - Self-reported needs for improving the supervision competence of PhD supervisors
      from the medical sciences in Denmark.
AB  - BACKGROUND: Quality of supervision is a major predictor for successful PhD
      projects. A survey showed that almost all PhD students in the Health Sciences in
      Denmark indicated that good supervision was important for the completion of their
      PhD study. Interestingly, approximately half of the students who withdrew from
      their program had experienced insufficient supervision. This led the Research
      Education Committee at the University of Copenhagen to recommend that supervisors
      further develop their supervision competence. The aim of this study was to
      explore PhD supervisors' self-reported needs and wishes regarding the content of
      a new program in supervision, with a special focus on the supervision of PhD
      students in medical fields. METHODS: A semi-structured interview guide was
      developed, and 20 PhD supervisors from the Graduate School of Health and Medical
      Sciences at the Faculty of Health and Medical Sciences at the University of
      Copenhagen were interviewed. Empirical data were analysed using qualitative
      methods of analysis. RESULTS: Overall, the results indicated a general interest
      in improved competence and development of a new supervision programme. Those who
      were not interested argued that, due to their extensive experience with
      supervision, they had no need to participate in such a programme. The analysis
      revealed seven overall themes to be included in the course. The clinical context
      offers PhD supervisors additional challenges that include the following sub
      themes: patient recruitment, writing the first article, agreements and scheduled
      appointments and two main groups of students, in addition to the main themes.
      CONCLUSIONS: The PhD supervisors reported the clear need and desire for a
      competence enhancement programme targeting the supervision of PhD students at the
      Faculty of Health and Medical Sciences. Supervision in the clinical context
      appeared to require additional competence. TRIAL REGISTRATION: The Scientific
      Ethical Committee for the Capital Region of Denmark. Number: H-3-2010-101, date:
      2010.09.29.

PMID- 29058585
TI  - Preliminary comparative genomics revealed pathogenic potential and international
      spread of Staphylococcus argenteus.
AB  - BACKGROUND: Staphylococcus argenteus and S. schweitzeri, were recently proposed
      as novel species within S. aureus complex (SAC). S. argenteus has been reported
      in many countries and can threaten human health. S. schweitzeri has not been
      associated with human infections, but has been isolated from non-human primates.
      Questions regarding the evolution of pathogenicity of these two species will
      remain elusive until an exploratory evolutionary framework is established.
      RESULTS: We present genomic comparison analysis among members of SAC based on a
      pan-genome definition, which included 15 S. argenteus genomes (five newly
      sequenced), six S. schweitzeri genomes and 30 divergent S. aureus genomes. The
      three species had divergent core genomes and rare interspecific recombination was
      observed among the core genes. However, some subtypes of staphylococcal cassette
      chromosome mec (SCCmec) elements and prophages were present in different species.
      Of 111 tested virulence genes of S. aureus, 85 and 86 homologous genes were found
      in S. argenteus and S. schweitzeri, respectively. There was no difference in
      virulence gene content among the three species, but the sequence of most core
      virulence genes was divergent. Analysis of the agr locus and the genes in the
      capsular polysaccharides biosynthetic operon revealed that they both diverged
      before the speciation of SAC members. Furthermore, the widespread geographic
      distribution of S. argenteus, sequence type 2250, showed ambiguous
      biogeographical structure among geographically isolated populations,
      demonstrating an international spread of this pathogen. CONCLUSIONS: S. argenteus
      has spread among several countries, and invasive infections and persistent
      carriage may be not limited to currently reported regions. S. argenteus probably
      had undergone a recent host adaption and can cause human infections with a
      similar pathogenic potential.

PMID- 29058587
TI  - Is sedentary behaviour just physical inactivity by another name?
AB  - The relationship between sedentary behaviour and physical activity and their role
      in the development of health conditions is an ongoing topic of research. This
      debate paper presents arguments in favour and against the statement: "Is
      sedentary behaviour just physical inactivity by another name?" The paper finishes
      with recommendations for future research in the field of sedentary behaviour,
      physical activity and public health.

PMID- 29058588
TI  - Effect of Infla-Kine supplementation on the gene expression of inflammatory
      markers in peripheral mononuclear cells and on C-reactive protein in blood.
AB  - BACKGROUND: Chronic inflammation is a predisposing factor to numerous
      degenerative diseases including cancer, heart failure and Alzheimer's disease.
      Infla-Kine is a natural supplement comprised of a proprietary blend of
      Lactobacillus fermentum extract, burdock seed (arctigenin), zinc, alpha lipoic
      acid, papaya enzyme and an enhanced absorption bio-curcumin complex (BCM-95(r)).
      METHODS: Infla-Kine was administered twice daily to 24 health volunteers for 4
      weeks. Quantitative RT-PCR was used to assess mRNA transcripts of IL-1b, IL8, IL
      6, NF-kappaB, and TNF-alpha from peripheral blood mononuclear cells (PBMC). C
      reactive protein (CRP) was measured from serum. Additionally, quality of life
      questionnaires were employed to assess general feeling of well-being. Assessments
      were made before treatment and at conclusion of treatment (4 weeks). RESULTS: As
      compared to pre-treatment, after 4 weeks, a statistically significant reduction
      of IL8, IL-6, NF-kappaB, and TNF-alpha transcripts was observed in PBMC.
      Furthermore, reduction of IL-1b transcript and serum CRP was observed but did not
      reach statistical significance. Quality of life improvements were most prevalent
      in muscle and joint pains. CONCLUSIONS: Overall, our data demonstrate that twice
      daily administration of Infla-Kine for 4 weeks reduces inflammatory markers and
      quality of life in healthy volunteers.

PMID- 29058590
TI  - Left ventricular geometry predicts ventricular tachyarrhythmia in patients with
      left ventricular systolic dysfunction: a comprehensive cardiovascular magnetic
      resonance study.
AB  - BACKGROUND: Most patients with implantable cardioverter-defibrillator (ICD)
      implantation fail to utilize the device resulting in increasing societal costs
      and patient exposure to device morbidity. We sought to determine whether
      volumetric cardiovascular magnetic resonance (CMR) left ventricular (LV)
      spherical remodeling predicts future ventricular arrhythmias in primary ICD
      patients with reduced LV ejection fraction (EF). METHODS: Sixty-eight consecutive
      patients with transthoracic echocardiographic LVEF <35% referred for CMR prior to
      ICD implantation for primary prevention of sudden death were identified.
      Sphericity index was measured as the ratio of LV end-diastolic volume (from cine
      short axis stack) to the volume of a sphere with a LV end-diastolic 4-chamber
      length diameter. RESULTS: During a median follow-up of 55 months (interquartile
      range; 28-88), 15 patients (22%) received appropriate ICD therapy. Multivariable
      Cox's proportional hazard modeling identified increased CMR-derived sphericity
      index as the strongest independent predictor of appropriate ICD therapy (hazard
      ratio [HR], 1.09; 95% confidence interval [CI], 1.02 to 1.16; p = 0.007). In
      addition, dichotomized volumetric CMR-derived sphericity index >=0.57 carried a 4
      fold hazard risk for appropriate ICD therapy, controlling for age and LVEF (HR,
      4.49; 95% CI, 1.53 to 13.21; p = 0.006). When sphericity index, LVEF and mass
      index were used in combination, important incremental prognostic information was
      achieved (net reclassification improvement, 0.42; 95% CI, 0.06 to 0.77).
      CONCLUSIONS: The combined assessment of LV geometry, mass index and systolic
      function may provide incremental prognostic information regarding ventricular
      arrhythmia requiring appropriate ICD therapy in primary prevention patients with
      reduced LVEF.

PMID- 29058589
TI  - Translational evidence for two distinct patterns of neuroaxonal injury in sepsis:
      a longitudinal, prospective translational study.
AB  - BACKGROUND: Brain homeostasis deteriorates in sepsis, giving rise to a mostly
      reversible sepsis-associated encephalopathy (SAE). Some survivors experience
      chronic cognitive dysfunction thought to be caused by permanent brain injury. In
      this study, we investigated neuroaxonal pathology in sepsis. METHODS: We
      conducted a longitudinal, prospective translational study involving (1)
      experimental sepsis in an animal model; (2) postmortem studies of brain from
      patients with sepsis; and (3) a prospective, longitudinal human sepsis cohort
      study at university laboratory and intensive care units (ICUs). Thirteen ICU
      patients with septic shock, five ICU patients who died as a result of sepsis,
      fourteen fluid-resuscitated Wistar rats with fecal peritonitis, eleven sham
      operated rats, and three human and four rat control subjects were included.
      Immunohistologic and protein biomarker analysis were performed on rat brain
      tissue at baseline and 24, 48, and 72 h after sepsis induction and in sham
      treated rats. Immunohistochemistry was performed on human brain tissue from
      sepsis nonsurvivors and in control patients without sepsis. The clinical
      diagnostics of SAE comprised longitudinal clinical data collection and magnetic
      resonance imaging (MRI) and electroencephalographic assessments. Statistical
      analyses were performed using SAS software (version 9.4; SAS Institute, Inc.,
      Cary, NC, USA). Because of non-Gaussian distribution, the nonparametric Wilcoxon
      test general linear models and the Spearman correlation coefficient were used.
      RESULTS: In postmortem rat and human brain samples, neurofilament phosphoform,
      beta-amyloid precursor protein, beta-tubulin, and H&E stains distinguished
      scattered ischemic lesions from diffuse neuroaxonal injury in septic animals,
      which were absent in controls. These two patterns of neuroaxonal damage were
      consistently found in septic but not control human postmortem brains. In
      experimental sepsis, the time from sepsis onset correlated with tissue
      neurofilament levels (R = 0.53, p = 0.045) but not glial fibrillary acidic
      protein. Of 13 patients with sepsis who had clinical features of SAE, MRI
      detected diffuse axonal injury in 9 and ischemia in 3 patients. CONCLUSIONS:
      Ischemic and diffuse neuroaxonal injury to the brain in experimental sepsis,
      human postmortem brains, and in vivo MRI suggest these two distinct lesion types
      to be relevant. Future studies should be focused on body fluid biomarkers to
      detect and monitor brain injury in sepsis. The relationship of neurofilament
      levels with time from sepsis onset may be of prognostic value. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02442986 . Registered on May 13, 2015.

PMID- 29058591
TI  - Proteomic analysis of trochophore and veliger larvae development in the small
      abalone Haliotis diversicolor.
AB  - BACKGROUND: Haliotis diversicolor is commercially important species. The
      trochophore and veliger are distinct larval stages in gastropod development.
      Their development involves complex morphological and physiological changes. We
      studied protein changes during the embryonic development of H. diversicolor using
      two dimensional electrophoresis (2-DE) and label-free methods, tandem mass
      spectrometry (MS/ MS), and Mascot for protein identification. RESULTS: A total of
      150 2-DE gel spots were identified. Protein spots showed upregulation of 15
      proteins and downregulation of 28 proteins as H. diversicolor developed from
      trochophore to veliger larvae. Trochophore and veliger larvae were compared using
      a label-free quantitative proteomic approach. A total of 526 proteins were
      identified from both samples, and 104 proteins were differentially expressed (>
      1.5 fold). Compared with trochophore larvae, veliger larvae had 55 proteins
      upregulated and 49 proteins downregulated. These differentially expressed
      proteins were involved in shell formation, energy metabolism, cellular and stress
      response processes, protein synthesis and folding, cell cycle, and cell fate
      determination. Compared with the 5 protein (fructose-bisphosphate aldolase, 14-3
      3epsilon, profilin, actin-depolymerizing factor (ADF)/cofilin) and calreticulin)
      expression patterns, the mRNA expression exhibited similar patterns except gene
      of fructose-bisphosphate aldolase. CONCLUSION: Our results provide insight into
      novel aspects of protein function in shell formation, torsion, and nervous system
      development, and muscle system differentiation in H. diversicolor larvae.
      "Quality control" proteins were identified to be involved in abalone larval
      development.

PMID- 29058592
TI  - Ureteral reconstruction using a tapered non-vascularized bladder graft: an
      experimental study in a canine animal model.
AB  - BACKGROUND: Reconstruction of ureteral defects and strictures remains problematic
      for urologists. We aimed to investigate the possibility of a tapered non
      vascularized bladder graft as a novel substitute for ureteral reconstruction.
      METHODS: This experimental study was conducted on nine beagles. Under general
      anesthesia, a full-thickness graft with 5-6 cm in length was disassociated from
      the anterior upper wall of the bladder, and tapered into 1/3 to 1/2 thickness,
      remaining the urothelial surface. After removal of 5 cm of right-sided mid
      ureter, the tapered bladder graft was tubularized along the long axis and then
      respectively anastomosed to the upper and lower stumps of the ureter. A
      retrograde urography through a cystostomy was performed 8 weeks after the
      ureteral reconstruction. The animals were euthanized, and histopathologic
      examinations of the neoureters were performed. RESULTS: There were no severe
      complications during postoperative follow-up. The urography indicated patent
      urine excretion and no fistula or stenosis. Histopathologic examinations of the
      neoureters showed open lumen with urothelial lining. Nutrient vessels were
      observed in healthy submucosa, lamina muscularis and peripheral connective
      tissue. CONCLUSIONS: Our study implied that ureteral reconstruction by a tapered
      non-vascularized bladder graft was anatomically possible in our animal model.
      Further studies are expected to confirm long-term and functional outcomes.

PMID- 29058593
TI  - Brain donation in psychiatry: results of a Dutch prospective donor program among
      psychiatric cohort participants.
AB  - BACKGROUND: Human brain tissue is crucial to study the molecular and cellular
      basis of psychiatric disorders. However, the current availability of human brain
      tissue is inadequate. Therefore, the Netherlands Brain Bank initiated a program
      in which almost 4.000 participants of 15 large Dutch psychiatric research cohorts
      were asked to register as prospective brain donors. METHODS: We approached
      patients with schizophrenia, bipolar disorder, major depressive disorder,
      obsessive-compulsive disorder, post-traumatic stress disorder, families with a
      child with autism or Attention Deficit Hyperactivity Disorder, healthy relatives
      and healthy unrelated controls, either face-to-face or by post. We investigated
      whether diagnosis, method of approach, age, and gender were related to the
      likelihood of brain-donor registration. RESULTS: We found a striking difference
      in registration efficiency between the diagnosis groups. Patients with bipolar
      disorder and healthy relatives registered most often (25% respectively 17%),
      followed by unrelated controls (8%) and patients with major depressive disorder,
      post-traumatic stress disorder, and obsessive-compulsive disorder (9%, 6% resp.
      5%). A face-to-face approach was 1.3 times more effective than a postal approach
      and the likelihood of registering as brain donor significantly increased with
      age. Gender did not make a difference. CONCLUSIONS: Between 2013 and 2016, our
      prospective brain-donor program for psychiatry resulted in an almost eightfold
      increase (from 149 to 1149) in the number of registered psychiatric patients at
      the Netherlands Brain Bank. Based on our results we recommend, when starting a
      prospective brain donor program in psychiatric patients, to focus on face to face
      recruitment of people in their sixties or older.

PMID- 29058594
TI  - From action planning and plan enactment to fruit consumption: moderated mediation
      effects.
AB  - OBJECTIVES: Sufficient fruit consumption is beneficial for a healthy live. While
      many Dutch adults intent to eat the recommended amount of fruit, only 5-10% of
      the population actually adheres to the recommendation. One mechanism that can
      help to narrow this gap between intention and actual fruit consumption is action
      planning. However, action planning is only assumed to be effective if plans are
      enacted. This study assessed which action plans are made and enacted, and further
      aimed to investigate two main hypotheses: 1. the effect of action planning (at
      T1) on fruit consumption (at T2) is mediated by plan enactment (at T3); 2.
      positive intentions (2a), high self-efficacy (2b) and a strong habit to eat fruit
      (2c) enhance the mediation of plan enactment, whereas a strong habit to eat
      snacks (2d) hinders the mediation of plan enactment. METHODS: This study was a
      self-reported longitudinal online survey study. A total of 428 participants
      filled in a survey, measuring demographic factors (e.g. gender, age, education
      level), several socio-cognitive constructs (i.e. attitudes, self-efficacy, habit,
      action planning, plan enactment), and fruit consumption, at three points in time
      (baseline, after 1 month, and after 3 months). Mediation and moderated mediation
      analyses were used to investigate the planning-plan enactment- fruit consumption
      relationship. RESULTS: Up to 70% of the participants reported to have enacted
      their T1 action plans at T2. Action planning on fruit consumption was fully
      mediated by plan enactment (Hypothesis 1). All four proposed moderators (i.e.
      intention, self-efficacy, habit to consume fruit, and habit to consume snacks)
      significantly influenced the mediation (Hypotheses 2a-2d). Mediation of plan
      enactment was only present with high levels of intention, high levels of self
      efficacy, strong habits to eat fruit, and weak habits to eat snacks. CONCLUSION:
      The study suggests the importance of plan enactment for fruit consumption.
      Furthermore, it emphasizes the necessity of facilitating factors. High levels of
      intention, self-efficacy and a strong habit to consume fruit clearly aid the
      enactment of action plans. This suggests that when these factors are moderately
      low, plan enactment may fail and thus an intervention may require first steps to
      foster these moderating factors.

PMID- 29058595
TI  - World-Wide Immunoscore Task Force: meeting report from the "Melanoma Bridge",
      Napoli, November 30th-December 3rd, 2016.
AB  - The predictive accuracy of the traditional staging system is based on disease
      progression as a tumour cell-autonomous process, but it fails to incorporate the
      effects of the host immune response. A precise analysis of the immune component
      of the tumour microenvironment by computer-based analysis may be essential to
      managing patients better, opening the road to an expertise in this new emerging
      field. The Immunoscore as a new possible approach in the classification of
      cancer, designated TNM-Immune, studied in colon cancer patients with predictive
      and prognostic value. This new scoring system is derived from the immune
      contexture, and is based on the numeration of lymphocyte populations, both in the
      core of the tumour and in the invasive margin of tumours. The Immunoscore
      demonstrated to be quantitative, reproducible and robust. The usefulness of
      Immunoscore in advanced melanoma cancer patients has been as well demonstrated;
      the correlation of marker expression profile with clinical outcome is ongoing.
      More recently, the Immunoscore could be a useful prognostic marker in patients
      with rectal cancer treated by primary surgery. A multivariable Cumulative
      "Suppression Index" scoring system has been also studied in Oral Squamous Cell
      Carcinoma patients: it evaluates both the tumor and stromal microcompartments at
      the invasive margin and summarizes them into the score, providing an accurate
      stratification, independent of stage, tumour classification. The introduction of
      Immunoscore requires a redefinition of the Laboratory system according to the
      LEAN Management process, which has been already implemented in referral research
      labs. The definition and test of hundreds of biomarkers, in the tumour contexture
      represents a definitive scientific progression. However, there is still a need of
      substantial body of work to reach the end of the tunnel to assure a personalize
      treatment.

PMID- 29058596
TI  - Efficacy of inhaled HYdrogen on neurological outcome following BRain Ischemia
      During post-cardiac arrest care (HYBRID II trial): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Hydrogen gas inhalation (HI) improved survival and neurological
      outcomes in an animal model of post-cardiac arrest syndrome (PCAS). The
      feasibility and safety of HI for patients with PCAS was confirmed in a pilot
      study. The objective of this study is to evaluate the efficacy of HI for patients
      with PCAS. METHODS/DESIGN: The efficacy of inhaled HYdrogen on neurological
      outcome following BRain Ischemia During post-cardiac arrest care (HYBRID II)
      trial is an investigator-initiated, randomized, double-blind, placebo-controlled
      trial designed to enroll 360 adult comatose (Glasgow Coma Scale score < 8)
      patients who will be resuscitated following an out-of-hospital cardiac arrest of
      a presumed cardiac cause. The patients will be randomized (1:1) to either the HI
      or control group. Patients in the HI group will inhale 2% hydrogen with 24% to
      50% oxygen, and those in the control group will inhale 24% to 50% oxygen for 18 h
      after admission via mechanical ventilation. Multidisciplinary post-arrest care,
      including targeted temperature management (TTM) between 33  degrees C and 36 
      degrees C, will be provided in accordance with the latest guidelines. The primary
      outcome of interest is the 90-day neurological outcome, as evaluated using the
      Cerebral Performance Categories scale (CPC). The secondary outcomes of interest
      are the 90-day survival rate and other neurological outcomes. This study will
      provide 80% power to detect a 15% change in the proportion of patients with good
      neurological outcomes (CPCs of 1 and 2), from 50% to 65%, with an overall
      significance level of 0.05. DISCUSSION: The first multicenter randomized trial is
      underway to confirm the efficacy of HI on neurological outcomes in comatose out
      of-hospital cardiac arrest survivors. Our study has the potential to address HI
      as an appealing and innovative therapeutic strategy for PCAS in combination with
      TTM. TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN),
      000019820 . Registered on 17 November 2015.

PMID- 29058597
TI  - Correction to: Disruption of endothelial adherens junctions by high glucose is
      mediated by protein kinase C-beta-dependent vascular endothelial cadherin
      tyrosine phosphorylation.
AB  - This article was unintentionally published twice in this journal, by the same
      authors. The following should be considered the version of record and used for
      citation purposes: "Mehran Haidari, Wei Zhang, James T Willerson and Richard AF
      Dixon, Disruption of endothelial adherens junctions by high glucose is mediated
      by protein kinase C-beta-dependent vascular endothelial cadherin tyrosine
      phosphorylation, Cardiovascular Diabetology, Volume 13, Issue 1, doi:
      10.1186/1475-2840-13-112 ". The duplicate "Mehran Haidari, Wei Zhang, James T
      Willerson and Richard AF Dixon, Disruption of endothelial adherens junctions by
      high glucose is mediated by protein kinase C-beta-dependent vascular endothelial
      cadherin tyrosine phosphorylation, Cardiovascular Diabetology, Volume 13, Issue
      1, doi: 10.1186/1475-2840-13-105 " is to be ignored. The Publisher apologizes to
      the readers of the journal for not detecting the duplication during the
      publication process.

PMID- 29058598
TI  - Validity of self-reported breast cancer characteristics in a nationwide cohort of
      women with a family history of breast cancer.
AB  - BACKGROUND: Women may have incomplete understanding of a breast cancer diagnosis,
      leading to inaccurate reporting in epidemiological studies. However, it is not
      feasible to obtain consent for medical records from all women participating in a
      study. Therefore, it is important to determine how well self-reported breast
      cancer characteristics correspond with what is found in medical records, but few
      studies have evaluated agreement of self-reported breast cancer characteristics
      with abstracted medical records. METHODS: We calculated the positive predictive
      value (PPV) of self-reports compared to medical records and explored whether
      participant characteristics may have influenced reporting accuracy. We analyzed
      data from 2518 reported breast cancer cases from the Sister Study, a large
      nationwide cohort of women with a family history of breast cancer. RESULTS:
      Medical records or pathology reports were obtained for 2066 of 2518 (82%) women
      who reported incident breast cancer. Breast cancer was confirmed for over 99% (n
      = 2054) of women with medical records. Confirmation rates were high for invasive,
      ductal, hormone receptor positive, and HER2 negative breast cancers, with little
      variation by race/ethnicity or age. Self-reported in situ breast cancer had a
      lower PPV (64.2%), with medical records showing invasive breast cancer instead,
      especially for older and Hispanic women. Hormone receptor (ER and PR) negative
      and HER2 positive self-reports had lower PPVs (83.0%, 71.6%, and 66.1%
      respectively). Hispanic women and women ages 65 or older at diagnosis were less
      able to accurately report breast cancer stage, excluding stage I. CONCLUSIONS:
      Accuracy of reporting overall breast cancer and common subtypes is high. Despite
      having a family history of breast cancer and voluntarily enrolling in a study
      evaluating breast cancer risk factors, participants may have greater difficulty
      distinguishing between in situ and invasive breast cancer and may less accurately
      report other less common subtypes. Discrepancies may reflect women's poor
      understanding of information conveyed by health care providers or lack of
      consistent terminology used to describe subtypes.

PMID- 29058600
TI  - Finding the precision to improve outcome in patients after cardiac arrest.

PMID- 29058599
TI  - Evidence of reduced recombination rate in human regulatory domains.
AB  - BACKGROUND: Recombination rate is non-uniformly distributed across the human
      genome. The variation of recombination rate at both fine and large scales cannot
      be fully explained by DNA sequences alone. Epigenetic factors, particularly DNA
      methylation, have recently been proposed to influence the variation in
      recombination rate. RESULTS: We study the relationship between recombination rate
      and gene regulatory domains, defined by a gene and its linked control elements.
      We define these links using expression quantitative trait loci (eQTLs),
      methylation quantitative trait loci (meQTLs), chromatin conformation from
      publicly available datasets (Hi-C and ChIA-PET), and correlated activity links
      that we infer across cell types. Each link type shows a "recombination rate
      valley" of significantly reduced recombination rate compared to matched control
      regions. This recombination rate valley is most pronounced for gene regulatory
      domains of early embryonic development genes, housekeeping genes, and
      constitutive regulatory elements, which are known to show increased evolutionary
      constraint across species. Recombination rate valleys show increased DNA
      methylation, reduced doublestranded break initiation, and increased repair
      efficiency, specifically in the lineage leading to the germ line. Moreover, by
      using only the overlap of functional links and DNA methylation in germ cells, we
      are able to predict the recombination rate with high accuracy. CONCLUSIONS: Our
      results suggest the existence of a recombination rate valley at regulatory
      domains and provide a potential molecular mechanism to interpret the interplay
      between genetic and epigenetic variations.

PMID- 29058601
TI  - Role of renal function in risk assessment of target non-attainment after standard
      dosing of meropenem in critically ill patients: a prospective observational
      study.
AB  - BACKGROUND: Severe bacterial infections remain a major challenge in intensive
      care units because of their high prevalence and mortality. Adequate antibiotic
      exposure has been associated with clinical success in critically ill patients.
      The objective of this study was to investigate the target attainment of standard
      meropenem dosing in a heterogeneous critically ill population, to quantify the
      impact of the full renal function spectrum on meropenem exposure and target
      attainment, and ultimately to translate the findings into a tool for practical
      application. METHODS: A prospective observational single-centre study was
      performed with critically ill patients with severe infections receiving standard
      dosing of meropenem. Serial blood samples were drawn over 4 study days to
      determine meropenem serum concentrations. Renal function was assessed by
      creatinine clearance according to the Cockcroft and Gault equation (CLCRCG).
      Variability in meropenem serum concentrations was quantified at the middle and
      end of each monitored dosing interval. The attainment of two
      pharmacokinetic/pharmacodynamic targets (100%T>MIC, 50%T>4*MIC) was evaluated for
      minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard
      meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we
      assessed the impact of CLCRCG on meropenem concentrations and target attainment
      and developed a tool for risk assessment of target non-attainment. RESULTS: Large
      inter- and intra-patient variability in meropenem concentrations was observed in
      the critically ill population (n = 48). Attainment of the target 100%T>MIC was
      merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and
      similar for the target 50%T>4*MIC. A hyperbolic relationship between CLCRCG (25
      255 ml/minute) and meropenem serum concentrations at the end of the dosing
      interval (C8h) was derived. For infections with pathogens of MIC 2 mg/L, mild
      renal impairment up to augmented renal function was identified as a risk factor
      for target non-attainment (for MIC 8 mg/L, additionally, moderate renal
      impairment). CONCLUSIONS: The investigated standard meropenem dosing regimen
      appeared to result in insufficient meropenem exposure in a considerable fraction
      of critically ill patients. An easy- and free-to-use tool (the MeroRisk
      Calculator) for assessing the risk of target non-attainment for a given renal
      function and MIC value was developed. TRIAL REGISTRATION: Clinicaltrials.gov,
      NCT01793012 . Registered on 24 January 2013.

PMID- 29058604
TI  - Correction to: medical students can teach communication skills - a mixed methods
      study of cross-year peer tutoring.

PMID- 29058602
TI  - The crosstalk between autophagic and endo-/exosomal pathways in antigen
      processing for MHC presentation in anticancer T cell immune responses.
AB  - T cells recognize antigen fragments from proteolytic products that are presented
      to them in the form of peptides on major histocompatibility complex (MHC)
      molecules, which is crucial for the T cell to identify infected or transformed
      cells. Autophagy, a process that delivers cytoplasmic constituents for lysosomal
      degradation, has been observed to provide a substantial source of intra- and
      extracellular antigens for MHC presentation to T cells, which will impact the
      tumor-specific immune response. Meanwhile, extracellular components are
      transported to cytoplasm for the degradation/secretion process by the endo
      /exosomal pathway and are thus involved in multiple physiological and
      pathological processes, including immune responses. Autophagy and endo-/exosomal
      pathways are intertwined in a highly intricate manner and both are closely
      involved in antigen processing for MHC presentation; thus, we propose that they
      may coordinate in antigen processing and presentation in anticancer T cell immune
      responses. In this article, we discuss the molecular and functional crosstalk
      between autophagy and endo-/exosomal pathways and their contributions to antigen
      processing for MHC presentation in anticancer T cell immune responses.

PMID- 29058603
TI  - Incorporating religion and spirituality into the design of community-based
      physical activity programs for African American women: a qualitative inquiry.
AB  - OBJECTIVE: Limited research has examined how aspects of religion and spirituality
      can be incorporated into community-based physical activity programs delivered
      outside of religious institutions. The purpose of this study was to qualitatively
      explore how spirituality and religion can be leveraged in the design of community
      based physical activity programs for African American women delivered outside of
      faith-based or faith-placed settings. RESULTS: Three focus groups were conducted
      were conducted with 23 African American women (M age = 37.8 years, M BMI = 39.6
      kg m2). Results showed that incorporating aspects of spirituality (i.e., words
      encouraging connectedness to a higher power, meditation, mind-body activities)
      into a physical activity program was universally accepted among participants,
      regardless of religious affiliation. In contrast, including concepts of religion
      (i.e., bible verses and/or quotes from religious leaders) was controversial and
      not recommended among women who did not identify with a religious faith. Findings
      indicate that when developing community-based physical activity interventions
      that will not be delivered through faith-based or faith-placed settings,
      researchers should avoid references to specific religious beliefs. Instead,
      interventions should focus on spirituality and emphasize the mind-body
      relationship between physical activity and an African American women's inner
      being and her connectedness with a higher power. Trial Registration
      ClinicalTrials.gov NCT02823379. Registered July 1, 2016.

PMID- 29058605
TI  - Important knowledge gaps among pastoralists on causes and treatment of udder
      health problems in livestock in southern Ethiopia: results of qualitative
      investigation.
AB  - BACKGROUND: Ethiopia has high prevalences of udder health problems including
      clinical and subclinical mastitis across production systems in different
      livestock species. Previous studies on udder health problems have largely focused
      on identification of mastitis causing microbial pathogens and associated risk
      factors. However, relatively little is known about the knowledge and beliefs of
      livestock keepers regarding udder health problems. An understanding of the
      beliefs on the other hand would facilitate effective communication between
      livestock keepers and animal health professionals. Therefore, this study aimed at
      exploring the knowledge and belief surrounding the causes, clinical signs and
      treatments for udder health problems in (agro-) pastoral communities in southern
      Ethiopia using qualitative investigation. RESULTS: The result showed that udder
      health problem, locally known as 'dhukkuba muchaa', which translates to 'disease
      of teats', was classified into three main types: (1) tick infestation
      (dirandisa), (2) swelling of udder often with pus discharge (nyaqarsa) and (3)
      acute mastitis caused by evil eye (buda) with 'bloody milk'. Tick infestation was
      perceived to directly cause mechanical damage to udder tissue or to resulting in
      swelling leading to nyaqarsa. Our analysis also revealed the strong misperception
      that acute and severe swelling of udder was caused by evil eye. According to the
      pastoralists, cows with large udders in the late pregnancy are prone to evil eye
      infliction upon giving birth. The pastoralists often treat udder health problems
      by combining both modern and traditional methods. Removal of ticks by hand and
      acarcide application were the preferred methods for limiting tick infestation
      while swelling and evil eye cases were treated with antibiotics (e.g.
      oxytetracycline). The study also revealed that specific herbs, only known by the
      herbalists, were used for traditional treatment of udder health. Although this
      information could not be divulged at the time, it should form the subject of
      further investigation. Traditional treatment for evil eye was often administered
      through nostrils, raising questions about its effectiveness. CONCLUSION: The
      narration given by the pastoralists in associating tick infestation with udder
      health problems was compatible with existing scientific evidences. In this
      respect, such local knowledge can be better utilized for the educational messages
      targeting control and management of tick infestation in livestock. However, the
      misperception of causes for acute udder swelling as evil eye can be problematic
      as far as the application of appropriate treatment and management of the problem
      is concerned. The misperception can significantly impact the welfare of animals
      and highlights the need for capacity building of the pastoralists on the causes
      and treatment of udder health problems.

PMID- 29058606
TI  - Accuracy of serum luteinizing hormone and serum testosterone measurements to
      assess the efficacy of medical castration in prostate cancer patients.
AB  - BACKGROUND: Luteinizing hormone-releasing hormone (LH-RH) agonists are the
      standard for androgen deprivation therapy (ADT) in prostate cancer (PCa)
      patients. Current guidelines recommend serum testosterone measurement to assess
      the efficacy of ADT and to define castration resistance. However, serum
      testosterone does not reflect the exclusive effect of castration due to its
      extratesticular production. The aim of this study is to analyze if serum LH
      reflects better than serum testosterone the activity of LH-RH agonists. METHODS:
      Serum LH and serum testosterone were measured with chemiluminescent immunoassay
      (CLIA) in a cohort study of 1091 participants: 488 PCa patients "on LH-RH
      agonists", 303 "off LH-RH agonist" in whom LH-RH agonists were withdrawn, and 350
      men with PCa suspicion "no LH-RH agonist" who never received LH-RH agonists. In a
      validation cohort of 147 PCa patients, 124 on "LH-RH agonists" and 19 "off LH-RH
      agonists", serum testosterone was also measured with liquid chromatography and
      tandem mass spectrometry (LC MSMS). RESULTS: The area under the curve (AUC) to
      distinguish patients "on versus off LH-RH agonists" was 0.997 for serum LH and
      0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in
      patients "on LH-RH agonists" was 0.97 U/L, been the most efficient threshold 1.1
      U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in
      the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The
      efficacy to distinguish patients "on versus off LH-RH agonists" was 98.6%, 78.3%,
      and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for
      serum testosterone regardless the method. CONCLUSIONS: Serum LH is more accurate
      than serum testosterone regardless the method, to distinguish patients "on versus
      off LH-RH agonists". The castrate level of serum LH is 1.1 U/l. These findings
      suggest that assessment of LH-RH agonist efficacy and castration resistance
      definition should be reviewed.

PMID- 29058607
TI  - Aerosol delivery during invasive mechanical ventilation: a systematic review.
AB  - BACKGROUND: This systematic review aimed to assess inhaled drug delivery in
      mechanically ventilated patients or in animal models. Whole lung and regional
      deposition and the impact of the ventilator circuit, the artificial airways and
      the administration technique for aerosol delivery were analyzed. METHODS: In vivo
      studies assessing lung deposition during invasive mechanical ventilation were
      selected based on a systematic search among four databases. Two investigators
      independently assessed the eligibility and the risk of bias. RESULTS: Twenty-six
      clinical and ten experimental studies were included. Between 30% and 43% of
      nominal drug dose was lost to the circuit in ventilated patients. Whole lung
      deposition of up to 16% and 38% of nominal dose (proportion of drug charged in
      the device) were reported with nebulizers and metered-dose inhalers,
      respectively. A penetration index inferior to 1 observed in scintigraphic studies
      indicated major proximal deposition. However, substantial concentrations of
      antibiotics were measured in the epithelial lining fluid (887 (406-12,819) MUg/mL
      of amikacin) of infected patients and in sub-pleural specimens (e.g., 197 MUg/g
      of amikacin) dissected from infected piglets, suggesting a significant distal
      deposition. The administration technique varied among studies and may explain a
      degree of the variability of deposition that was observed. CONCLUSIONS: Lung
      deposition was lower than 20% of nominal dose delivered with nebulizers and
      mostly occurred in proximal airways. Further studies are needed to link
      substantial concentrations of antibiotics in infected pulmonary fluids to
      pulmonary deposition. The administration technique with nebulizers should be
      improved in ventilated patients in order to ensure an efficient but safe,
      feasible and reproducible technique.

PMID- 29058609
TI  - Characterization of the development of Haemonchus contortus ZJ strain from
      gerbils.
AB  - BACKGROUND: Haemonchus contortus is a serious parasitic nematode in domestic
      ruminants around the world, including China. Haemonchus contortus has developed
      extensive resistance to commercial anthelmintics, which has produced a demand for
      new control methods, such as more effective drugs. Gerbils infected with H.
      contortus have previously been used as a model for anthelmintics selections, and
      the growth of H. contortus had been briefly examined. To enhance the model, this
      study provides an additional description of the development of H. contortus ZJ
      strain in gerbils. RESULTS: Gerbils were infected with H. contortus ZJ strain at
      a dose of 2000 exsheathed infective larvae (xL3s) and sacrificed at 4, 7 and 18
      days post-infection (dpi). Only fourth-stage larvae were found in the stomachs.
      About 2% of the inoculums were obtained at each of the three sampling time
      points. Larvae grew more slowly in gerbils than in sheep, but presented almost
      the same morphology. Rod-like crystalline inclusions were present in the
      intestinal cells of larvae, indicating that the metabolic rate of larvae was
      probably greatly reduced. Histological examination of stomach sections showed
      that larvae are located in the lumens or at the mucosal surfaces, with few
      inflammatory changes evident. CONCLUSIONS: The development and features of H.
      contortus ZJ strain in gerbils were described. Our results provide supplementary
      information of H. contortus growth in gerbils, especially the presence of rod
      like crystalline inclusions, and may contribute to improve the anthelmintic
      selection system.

PMID- 29058608
TI  - In vivo phosphoproteome characterization reveals key starch granule-binding
      phosphoproteins involved in wheat water-deficit response.
AB  - BACKGROUND: Drought stress during grain development causes significant yield loss
      in cereal production. The phosphorylated modification of starch granule-binding
      proteins (SGBPs) is an important mechanism regulating wheat starch biosynthesis.
      In this study, we performed the first proteomics and phosphoproteomics analyses
      of SGBPs in elite Chinese bread wheat (Triticum aestivum L.) cultivar Jingdong 17
      under well-watered and water-stress conditions. RESULTS: Water stress treatment
      caused significant reductions in spike grain numbers and weight, total starch and
      amylopectin content, and grain yield. Two-dimensional gel electrophoresis
      revealed that the quantity of SGBPs was reduced significantly by water-deficit
      treatment. Phosphoproteome characterization of SGBPs under water-deficit
      treatment demonstrated a reduced level of phosphorylation of main starch
      synthesis enzymes, particularly for granule-bound starch synthase (GBSS I),
      starch synthase II-a (SS II-a), and starch synthase III (SS III). Specifically,
      the Ser34 site of the GBSSI protein, the Tyr358 site of SS II-a, and the Ser837
      site of SS III-a exhibited significant less phosphorylation under water-deficit
      treatment than well-watered treatment. Furthermore, the expression levels of
      several key genes related with starch biosynthesis detected by qRT-PCR were
      decreased significantly at 15 days post-anthesis under water-deficit treatment.
      Immunolocalization showed a clear movement of GBSS I from the periphery to the
      interior of starch granules during grain development, under both water-deficit
      and well-watered conditions. CONCLUSIONS: Our results demonstrated that the
      reduction in gene expression or transcription level, protein expression and
      phosphorylation levels of starch biosynthesis related enzymes under water-deficit
      conditions is responsible for the significant decrease in total starch content
      and grain yield.

PMID- 29058610
TI  - Whole genome population genetics analysis of Sudanese goats identifies regions
      harboring genes associated with major traits.
AB  - BACKGROUND: Sudan is endowed with a variety of indigenous goat breeds which are
      used for meat and milk production and which are well adapted to the local
      environment. The aim of the present study was to determine the genetic diversity
      and relationship within and between the four main Sudanese breeds of Nubian,
      Desert, Taggar and Nilotic goats. Using the 50 K SNP chip, 24 animals of each
      breed were genotyped. RESULTS: More than 96% of high quality SNPs were
      polymorphic with an average minor allele frequency of 0.3. In all breeds, no
      significant difference between observed (0.4) and expected (0.4) heterozygosity
      was found and the inbreeding coefficients (FIS) did not differ from zero. Fst
      coefficients for the genetic distance between breeds also did not significantly
      deviate from zero. In addition, the analysis of molecular variance revealed that
      93% of the total variance in the examined population can be explained by
      differences among individuals, while only 7% result from differences between the
      breeds. These findings provide evidence for high genetic diversity and little
      inbreeding within breeds on one hand, and low diversity between breeds on the
      other hand. Further examinations using Nei's genetic distance and STRUCTURE
      analysis clustered Taggar goats distinct from the other breeds. In a principal
      component (PC) analysis, PC1 could separate Taggar, Nilotic and a mix of Nubian
      and Desert goats into three groups. The SNPs that contributed strongly to PC1
      showed high Fst values in Taggar goat versus the other goat breeds. PCA allowed
      us to identify target genomic regions which contain genes known to influence
      growth, development, bone formation and the immune system. CONCLUSIONS: The
      information on the genetic variability and diversity in this study confirmed that
      Taggar goat is genetically different from the other goat breeds in Sudan. The
      SNPs identified by the first principal components show high Fst values in Taggar
      goat and allowed to identify candidate genes which can be used in the development
      of breed selection programs to improve local breeds and find genetic factors
      contributing to the adaptation to harsh environments.

PMID- 29058611
TI  - Adiponectin is required for maintaining normal body temperature in a cold
      environment.
AB  - BACKGROUND: Thermogenic impairment promotes obesity and insulin resistance.
      Adiponectin is an important regulator of energy homeostasis. While many
      beneficial metabolic effects of adiponectin resemble that of activated
      thermogenesis, the role of adiponectin in thermogenesis is not clear. In this
      study, we investigated the role of adiponectin in thermogenesis using adiponectin
      null mice (Adipoq -/-). METHODS: Body composition was measured using EchoMRI.
      Metabolic parameters were determined by indirect calorimetry. Insulin sensitivity
      was evaluated by glucose- and insulin- tolerance tests. Core body temperature was
      measured by a TH-8 temperature monitoring system. Gene expression was assessed by
      real-time PCR and protein levels were analyzed by Western blotting and
      immunohistochemistry. The mitochondrial density of brown adipose tissue was
      quantified by calculating the ratio of mtDNA:total nuclear DNA. RESULTS: Under
      normal housing temperature of 24  degrees C and ad libitum feeding condition, the
      body weight, body composition, and metabolic profile of Adipoq -/- mice were
      unchanged. Under fasting condition, Adipoq -/- mice exhibited reduced energy
      expenditure. Conversely, under cold exposure, Adipoq -/- mice exhibited reduced
      body temperature, and the expression of thermogenic regulatory genes was
      significantly reduced in brown adipose tissue (BAT) and subcutaneous white
      adipose tissue (WAT). Moreover, we observed that mitochondrial content was
      reduced in BAT and subcutaneous WAT, and the expression of mitochondrial fusion
      genes was decreased in BAT of Adipoq -/- mice, suggesting that adiponectin
      ablation diminishes mitochondrial biogenesis and altered mitochondrial dynamics.
      Our study further revealed that adiponectin deletion suppresses adrenergic
      activation, and down-regulates beta3-adrenergic receptor, insulin signaling, and
      the AMPK-SIRT1 pathway in BAT. CONCLUSIONS: Our findings demonstrate that
      adiponectin is an essential regulator of thermogenesis, and adiponectin is
      required for maintaining body temperature under cold exposure.

PMID- 29058613
TI  - Effect of interscalene block on intraocular pressure and ocular perfusion
      pressure.
AB  - BACKGROUND: Interscalene block (ISB) is commonly associated with Horner's
      syndrome due to spread of local anesthetic to the cervical sympathetic chain.
      Postganglionic neurons that originate from superior cervical ganglia form the
      sympathetic innervation of eye. Decrease in sympathetic tone may change
      intraocular pressure (IOP) and ocular perfusion pressure (OPP). The aim of the
      study was to investigate whether ISB affects IOP and/or OPP. METHODS: Thirty
      patients scheduled for ambulatory shoulder surgery under regional anesthesia with
      a single-shot ISB (15 mL 0.5% bupivacaine and 15 mL 2% lidocaine) were recruited.
      The IOP and OPP in both eyes, mean arterial pressure (MAP), heart rate (HR) and
      end-tidal CO2 (ETCO2) were measured before ISB and 5, 10, 20, 30 and 60 min after
      ISB in the beach-chair position. RESULTS: The baseline IOP and OPP were similar
      in the blocked and unblocked sides (IOP 17.60 +/- 1.69 and 17.40 +/- 1.96
      respectively p = 0.432; OPP 49.80 +/- 8.20 and 50 +/- 8.07 respectively p =
      0.432). The IOP in the blocked side significantly decreased between 10th to 60th
      min following ISB, compared to the baseline values (p < 0.001). The OPP in the
      blocked side significantly increased from 10th to 60th min (p < 0.001) whereas,
      there were no significant changes in IOP and OPP throughout the measurement
      period in the unblocked side. CONCLUSIONS: ISB decreased IOP in the blocked side.
      ISB could be considered as a safe regional technique of choice in elderly
      patients at high risk for developing glaucoma.

PMID- 29058612
TI  - Skeletal muscle mechanics, energetics and plasticity.
AB  - The following papers by Richard Lieber (Skeletal Muscle as an Actuator), Thomas
      Roberts (Elastic Mechanisms and Muscle Function), Silvia Blemker (Skeletal Muscle
      has a Mind of its Own: a Computational Framework to Model the Complex Process of
      Muscle Adaptation) and Sabrina Lee (Muscle Properties of Spastic Muscle (Stroke
      and CP) are summaries of their representative contributions for the session on
      skeletal muscle mechanics, energetics and plasticity at the 2016 Biomechanics and
      Neural Control of Movement Conference (BANCOM 2016). Dr. Lieber revisits the
      topic of sarcomere length as a fundamental property of skeletal muscle
      contraction. Specifically, problems associated with sarcomere length non
      uniformity and the role of sarcomerogenesis in diseases such as cerebral palsy
      are critically discussed. Dr. Roberts then makes us aware of the (often
      neglected) role of the passive tissues in muscles and discusses the properties of
      parallel elasticity and series elasticity, and their role in muscle function.
      Specifically, he identifies the merits of analyzing muscle deformations in three
      dimensions (rather than just two), because of the potential decoupling of the
      parallel elastic element length from the contractile element length, and reviews
      the associated implications for the architectural gear ratio of skeletal muscle
      contraction. Dr. Blemker then tackles muscle adaptation using a novel way of
      looking at adaptive processes and what might drive adaptation. She argues that
      cells do not have pre-programmed behaviors that are controlled by the nervous
      system. Rather, the adaptive responses of muscle fibers are determined by sub
      cellular signaling pathways that are affected by mechanical and biochemical
      stimuli; an exciting framework with lots of potential. Finally, Dr. Lee takes on
      the challenging task of determining human muscle properties in vivo. She
      identifies the dilemma of how we can demonstrate the effectiveness of a
      treatment, specifically in cases of muscle spasticity following stroke or in
      children with cerebral palsy. She then discusses the merits of ultrasound based
      elastography, and the clinical possibilities this technique might hold. Overall,
      we are treated to a vast array of basic and clinical problems in skeletal muscle
      mechanics and physiology, with some solutions, and many suggestions for future
      research.

PMID- 29058614
TI  - Psychometric characteristics of the chronic Otitis media questionnaire 12 (COMQ -
      12): stability of factor structure and replicability shown by the Serbian
      version.
AB  - BACKGROUND: Recently, demand for and supply of short-form patient-reported
      outcome measures (PROMs) have risen throughout the world healthcare. Our
      contribution to meeting that demand has been translating and culturally adapting
      the Chronic Otitis Media Questionnaire-12 (COMQ-12) for adults into Serbian and
      enhancing its psychometric base on the relatively large Serbian COM caseload.
      Chronic otitis media can seriously affect quality of life progressively and in
      long-term, and it remains the major source of hearing problems in the developing
      world. METHODS: The translated questionnaire was given twice to 60 adult patients
      with chronic otitis media of three types (inactive, active mucosal and active
      squamous disease) and to 60 healthy volunteers. Both patients and volunteers also
      filled the generic Short-Form 36 questionnaire (SF-36). Conventional statistical
      procedures were used in strategically driven development of scoring.
      Additionally, item responses were scaled by linear mapping against the
      provisional total score. Generalizability, detailed factor interpretation and
      supportability of scores were criteria, for the best compromise factor solution.
      RESULTS: Test-retest reliability was very high (0.924 to 0.989, depending on
      score). The a priori content dimensions of the questionnaire were strongly
      supported by 3-factor exploratory and confirmatory factor analyses for content
      validity, separating (i) ear symptoms from (ii) hearing problems, from (iii)
      daily activity restriction plus healthcare uptake. The 3-factor structure was
      furthermore highly stable on replication. The very large effect sizes when
      contrasting patients with healthy volunteers, and active with inactive disease
      established construct validity for the total score. A strong association with
      disease activity and a moderate one with generic health-related quality of life
      (HRQoL), the SF-36, supported construct validity for two of three factors
      extracted (ear symptoms, and impact on daily activities plus healthcare uptake).
      CONCLUSIONS: Given the minimal psychometric work to date on COMQ-12, this interim
      sample with 120 data points adds materially to knowledge of its reliability,
      several forms of validity and the feasibility of profile sub-scores to supplement
      total scores. The good psychometric properties shown for COMQ-12 justify both its
      routine clinical use and acquisition of the necessarily larger sample for
      generality, score optimisation and the evaluation of responsiveness.

PMID- 29058616
TI  - Correction to: Novel SNP markers in InvGE and SssI genes are associated with
      natural variation of sugar contents and frying color in Solanum tuberosum Group
      Phureja.

PMID- 29058615
TI  - Defatting of acetone leaf extract of Acacia karroo (Hayne) enhances its
      hypoglycaemic potential.
AB  - BACKGROUND: Conventional drugs used to treat diabetes are too expensive, toxic
      and rarely available to rural communities. This study was aimed at investigating
      the phytochemical differences and hypoglycaemic effects (alpha-amylase enzyme
      inhibition, glucose uptake, GLUT4 translocation and phosphorylation of MAPKs) of
      non-defatted and defatted acetone leaf extract of Acacia karroo. METHODS:
      Qualitative phytochemical analyses of extracts were determined using standard
      chemical tests and total phenolic contents using the Folin-Ciocalteu reagent
      method. Presence of antioxidant constituents was determined using DPPH scavenging
      and ferric reducing power assays. Alpha amylase enzyme inhibitory potential was
      determined chromogenically and cytotoxicity of the extracts on C2C12 muscle and
      3T3-L1 cells using the MTT assay. Glucose uptake by the cells was determined
      colorimetrically and the most active extract was evaluated for its ability to
      translocate GLUT4 and MAPKs phosphorylation potential using immunofluorescence
      microscopy and dot blot analysis, respectively. RESULTS: Phenols, flavonoids,
      tannins, saponins and cardiac glycosides were detected in both extracts.
      Defatting of the plant material resulted in low amounts of phenols (0.432 +/-
      0.014 TAE/mg), DPPH scavenging activity (EC50 0.40 +/- 0.012 mg/ml), low toxicity
      and high ferric reducing power (EC50 1.13 +/- 0.017 mg/ml), alpha-amylase enzyme
      inhibition (IC50 30.2 +/- 3.037 MUg/ml) and glucose uptake by both cells. The
      defatted extract showed an increase in GLUT4 translocation (at 25 MUg/ml) with
      decrease in Akt expression while in combination with insulin showed a decrease in
      GLUT4 translocation. A finding, that is implicative that the effect of the
      extract on GLUT4 translocation in C2C12 cells was not Akt dependent. The defatted
      extract in the absence and presence of insulin show varying phosphorylation
      levels of CREB, p38, GSK-3 and ERK2 which are important in cell survival and
      metabolism. CONCLUSION: This study represents the first report on the
      hypoglycemic potential of A. karroo and presence of compounds that can be
      exploited in the search for therapeutics with antidiabetic effect.

PMID- 29058617
TI  - Diagnostic accuracy of VIKIA(r) Rota-Adeno and PremierTM Rotaclone(r) tests for
      the detection of rotavirus in Niger.
AB  - OBJECTIVE: We conducted a parallel evaluation of the diagnostic accuracy of
      VIKIA(r) Rota-Adeno, a rapid diagnostic test (RDT) and PremierTM Rotaclone(r) an
      enzyme immunoassay (EIA) using reverse transcription polymerase chain reaction
      (RT-PCR) as the reference standard. The study was part of a rotavirus
      surveillance project in Niger. RESULTS: The sensitivity of both tests was 80.7%.
      After exclusion of one indeterminate result by visual reading, the specificity of
      the PremierTM Rotaclone(r) was 100% by visual or optical density readings and
      that of VIKIA(r) Rota-Adeno test was 95.5%. Inter-reader agreement was excellent
      for both tests (kappa = 1). Our results showed almost similar performance of the
      EIA and RDT when compared to RT-PCR. Hence, the VIKIA(r) Rota-Adeno could be a
      good alternative for use in peripheral health centres where laboratory capacity
      is limited.

PMID- 29058619
TI  - A large bladder stone caused by the intravesical migration of an intrauterine
      contraceptive device: a case report.
AB  - BACKGROUND: A wide variety of complications due to the extrauterine migration of
      intrauterine contraceptive devices have been reported in the literature. Here we
      describe the case of a large bladder stone formed around a migrated Copper T380A
      device that was neglected and detected 15 years after insertion. CASE
      PRESENTATION: A 48-year-old Sri Lankan woman underwent a workup for lower urinary
      tract symptoms and recurrent urinary tract infections over the previous 6 months.
      The radiographs showed a large bladder stone with an imprint of an intrauterine
      contraceptive device in the center of it. The device had been inserted 15 years
      previously. Two years after the insertion, it was considered to be missing, but
      our patient did not comply with the recommended follow-up. She had been
      completely asymptomatic until she developed lower urinary tract symptoms. After
      confirming the location of the stone via ultrasonography, a vesicolithotomy was
      performed, revealing a stone with three limbs corresponding to the shape of the
      Copper T380A device. The device and the threads were fully covered with the stone
      material. Our patient was asymptomatic following the surgery. CONCLUSIONS: A
      migrated intrauterine contraceptive device can act as the nidus for the formation
      of a secondary bladder stone. The detailed imprint of the device inside the stone
      and the laminated appearance of the stone material were characteristic of a
      secondary bladder stone formed around an intrauterine contraceptive device.
      Radiography and ultrasonography are adequate for the diagnosis of intravesical
      migration of intrauterine contraceptive devices.

PMID- 29058618
TI  - In silico analysis of the grapefruit sRNAome, transcriptome and gene regulation
      in response to CTV-CDVd co-infection.
AB  - BACKGROUND: Small RNA (sRNA) associated gene regulation has been shown to play a
      significant role during plant-pathogen interaction. In commercial citrus orchards
      co-infection of Citrus tristeza virus (CTV) and viroids occur naturally. METHODS:
      A next-generation sequencing-based approach was used to study the sRNA and
      transcriptional response in grapefruit to the co-infection of CTV and Citrus
      dwarfing viroid. RESULTS: The co-infection resulted in a difference in the
      expression of a number of sRNA species when comparing healthy and infected
      plants; the majority of these were derived from transcripts processed in a phased
      manner. Several RNA transcripts were also differentially expressed, including
      transcripts derived from two genes, predicted to be under the regulation of
      sRNAs. These genes are involved in plant hormone systems; one in the abscisic
      acid, and the other in the cytokinin regulatory pathway. Additional analysis of
      virus- and viroid-derived small-interfering RNAs (siRNAs) showed areas on the
      pathogen genomes associated with increased siRNA synthesis. Most interestingly,
      the starting position of the p23 silencing suppressor's sub-genomic RNA generated
      a siRNA hotspot on the CTV genome. CONCLUSIONS: This study showed the involvement
      of various genes, as well as endogenous and exogenous RNA-derived sRNA species in
      the plant-defence response. The results highlighted the role of sRNA-directed
      plant hormone regulation during biotic stress, as well as a counter-response of
      plants to virus suppressors of RNA-silencing.

PMID- 29058620
TI  - POWERS forID: Personalized Online Weight and Exercise Response System for
      Individuals with Intellectual Disability: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Intellectual disability (ID) is characterized by limitations in
      intellectual functioning and adaptive behavior. Adults with ID exhibit higher
      rates of obesity and poorer health status compared to the general population.
      Continuity of care and barriers to health-related activities may contribute to
      the poorer health status observed in this population. To address this problem, a
      tailored weight management online health information and communication technology
      platform, known as POWERSforID, was developed and is being tested to determine if
      this delivery mechanism can improve weight maintenance/weight loss in adults with
      ID. METHODS: Obese adults with mild-to-moderate ID (n = 70) are randomized to the
      POWERS forID intervention or control group for a 24-week trial. Each group
      undergoes an assessment that includes body weight, waist circumference, and
      percent body fat at baseline and at weeks 6, 12, and 24. Physical activity
      barriers, healthy eating barriers, food frequency, and psychosocial wellbeing are
      measured at baseline and at weeks 12 and 24. Blood lipids are assessed at
      baseline and 24 weeks. Participants randomized to POWERS forID receive access to
      the POWERS forID website and calls from a health coach (weekly during weeks 1-12,
      biweekly during weeks 13-24). The health coach employs motivational interviewing
      techniques adapted for individuals with ID to promote behavior change.
      Participants randomized to the control group receive standard clinical weight
      loss care. Differences in weight, waist circumference, blood lipids, percent body
      fat, and psychosocial self-report will be assessed. Barriers and facilitators of
      implementation as well as perception of study outcomes will be conducted via
      qualitative analysis. DISCUSSION: POWERS forID is a novel information and
      communication technology platform designed to address health needs for adults
      with ID. This article describes the development and components of POWERS forID.
      The overall aim is to assess usability and feasibility of POWERS forID for
      promoting weight loss for obese adults with ID over the course of a 24-week
      randomized control trial. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03139760 .
      Registered on XXX.

PMID- 29058622
TI  - Adverse drug effects observed with vildagliptin versus pioglitazone or
      rosiglitazone in the treatment of patients with type 2 diabetes mellitus: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Vildagliptin and pioglitazone/rosiglitazone are emerging Oral
      Hypoglycemic Agents (OHAs) which are used to treat patients suffering from Type 2
      Diabetes Mellitus (T2DM). In this analysis, we aimed to systematically compare
      the adverse drug events which were observed with the use of vildagliptin versus
      pioglitazone or rosiglitazone respectively. METHODS: Online databases were
      searched for studies comparing vildagliptin with pioglitazone/rosiglitazone.
      Adverse drug events were considered as the clinical endpoints in this analysis.
      We calculated Odds Ratios (OR) with 95% Confidence Intervals (CIs) using the
      RevMan 5.3 software. All the authors had full access to the data which were used
      and approved the final version of the manuscript. RESULTS: A total number of 2396
      patients were analyzed (1486 and 910 patients were treated with vildagliptin and
      pioglitazone/rosiglitazone respectively). Vildagliptin and
      pioglitazone/rosiglitazone were both associated with similar overall adverse drug
      events (OR: 1.00, 95% CI: 0.81-1.24; P = 1.00). Headache (OR: 0.88, 95% CI: 0.60
      1.27; P = 0.49) and upper respiratory tract infection (OR: 0.95, 95% CI: 0.71
      1.27; P = 0.75) were similarly observed. However, dizziness was significantly
      lower with pioglitazone/rosiglitazone (OR: 0.63, 95% CI: 0.43-0.92; P = 0.02).
      Back pain, diarrhea and nausea were insignificantly lower with
      pioglitazone/rosiglitazone (OR: 0.81, 95% CI: 0.49-1.33; P = 0.40), (OR: 0.83,
      95% CI: 0.48-1.44; P = 0.52) and (OR: 0.52, 95% CI: 0.25-1.05; P = 0.07)
      respectively, whereas peripheral edema and weight gain were insignificantly
      higher (OR: 1.21, 95% CI: 0.56-2.62; P = 0.63) and (OR: 2.29, 95% CI: 0.51-10.34;
      P = 0.28) respectively. Nevertheless, when pioglitazone and rosiglitazone were
      separately compared with vildagliptin, peripheral edema and weight gain were
      significantly higher with rosiglitazone (OR: 2.36, 95% CI: 1.40-3.99; P = 0.001)
      and (OR: 5.20, 95% CI: 2.47-10.92; P = 0.0001) respectively. CONCLUSION: Both
      vildagliptin and pioglitazone/rosiglitazone are acceptable for the treatment of
      patients with T2DM on the basis that they are not significantly different in
      terms of overall adverse drug events. However, weight gain and peripheral edema
      would have to be re-assessed in further larger randomized controlled trials.

PMID- 29058621
TI  - A systematic review and synthesis of the strengths and limitations of measuring
      malaria mortality through verbal autopsy.
AB  - BACKGROUND: Lack of valid and reliable data on malaria deaths continues to be a
      problem that plagues the global health community. To address this gap, the verbal
      autopsy (VA) method was developed to ascertain cause of death at the population
      level. Despite the adoption and wide use of VA, there are many recognized
      limitations of VA tools and methods, especially for measuring malaria mortality.
      This study synthesizes the strengths and limitations of existing VA tools and
      methods for measuring malaria mortality (MM) in low- and middle-income countries
      through a systematic literature review. METHODS: The authors searched PubMed,
      Cochrane Library, Popline, WHOLIS, Google Scholar, and INDEPTH Network Health and
      Demographic Surveillance System sites' websites from 1 January 1990 to 15 January
      2016 for articles and reports on MM measurement through VA. INCLUSION CRITERIA:
      article presented results from a VA study where malaria was a cause of death;
      article discussed limitations/challenges related to measurement of MM through VA.
      Two authors independently searched the databases and websites and conducted a
      synthesis of articles using a standard matrix. RESULTS: The authors identified
      828 publications; 88 were included in the final review. Most publications were VA
      studies; others were systematic reviews discussing VA tools or methods;
      editorials or commentaries; and studies using VA data to develop MM estimates.
      The main limitation were low sensitivity and specificity of VA tools for
      measuring MM. Other limitations included lack of standardized VA tools and
      methods, lack of a 'true' gold standard to assess accuracy of VA malaria
      mortality. CONCLUSIONS: Existing VA tools and methods for measuring MM have
      limitations. Given the need for data to measure progress toward the World Health
      Organization's Global Technical Strategy for Malaria 2016-2030 goals, the malaria
      community should define strategies for improving MM estimates, including
      exploring whether VA tools and methods could be further improved. Longer term
      strategies should focus on improving countries' vital registration systems for
      more robust and timely cause of death data.

PMID- 29058623
TI  - Trends in domain-specific physical activity and sedentary behaviors among Chinese
      school children, 2004-2011.
AB  - BACKGROUND: Dramatic increases in child overweight have occurred in China. A
      comprehensive look at trends in physical activity and sedentary behaviors among
      Chinese youth is needed. The study aimed to examine trends in domain-specific
      physical activity and sedentary behaviors, explore mean and distributional
      changes in predicted behaviors over time, and investigate how behaviors vary by
      residence. METHODS: Using 2004-2011 China Health and Nutrition Survey data,
      adjusted means for MET-hours/week from physical activity and hours/week from
      sedentary behaviors were determined for school children (6-18 years), stratifying
      by gender, age group, and residence. Physical activity domains included in-school
      physical activity, active leisure (out-of-school physical activity), active
      travel (walking or biking), and domestic activity (cooking, cleaning, and child
      care). For each physical activity domain, the MET-hours/week measure was
      determined from the total weekly time spent (hours) in domain-specific activities
      and corresponding MET-values using the Compendium of Energy Expenditures for
      Youth. Sedentary behaviors included television, computer use, homework, and other
      behaviors (board games, toys, extracurricular reading and writing). For each
      sedentary behavior, the hours/week measure was determined from total weekly time
      spent in specific sedentary behaviors. Residence groups included megacities
      (population >= 20million), cities/towns (300,000 <= population < 20million), and
      rural/suburban areas (population < 300,000). Repeated measure linear mixed and
      quantile regression models were used to predict adjusted means. RESULTS: Little
      change in physical activity behaviors occurred over time, with the exception of
      statistically significant trends toward increased domestic activity among male
      children (p < .05). Across all gender and age groups, statistically significant
      trends over time toward an average increase in computer use were seen (p < .01);
      these increases were largely driven by those >=50th percentile on the
      distribution. Children living in megacities (versus rural areas) reported higher
      levels of physical activity, homework, and computer use. CONCLUSIONS:
      Intensified, systematic intervention and policy efforts promoting physical
      activity and reducing sedentary behaviors among children are needed.

PMID- 29058624
TI  - Husk to caryopsis adhesion in barley is influenced by pre- and post-anthesis
      temperatures through changes in a cuticular cementing layer on the caryopsis.
AB  - BACKGROUND: At ripeness, the outer husk of "covered" barley grains firmly adheres
      to the underlying caryopsis. A cuticular cementing layer on the caryopsis is
      required for husk adhesion, however the quality of adhesion varies significantly
      among cultivars which produce the cementing layer, resulting in the economically
      important malting defect, grain skinning. The composition of the cementing layer,
      and grain organ development have been hypothesised to influence the quality of
      husk adhesion. Plants of Hordeum vulgare 'Concerto' were grown at different
      temperatures pre- and post-anthesis to effect changes in the development of the
      husk, caryopsis and cuticular cementing layer, to determine how these variables
      influence the quality of husk-to-caryopsis adhesion. RESULTS: Warm conditions pre
      anthesis decreased the quality of husk adhesion, and consequently increased the
      incidence of grain skinning. Cool post-anthesis conditions further decreased the
      quality of husk adhesion. The composition of the cementing layer, rather than its
      structure, differed with respect to husk adhesion quality. This cementing layer
      was produced at the late milk stage, occurring between nine and 29 days post
      anthesis, conditional on the temperature-dependent growth rate. The compounds
      octadecanol, tritriacontane, campesterol and beta-sitosterol were most abundant
      in caryopses with high-quality husk adhesion. The differences in adhesion quality
      were not due to incompatible husk and caryopsis dimensions affecting organ
      contact. CONCLUSIONS: This study shows that husk-to-caryopsis adhesion is
      dependent on cementing layer composition, and implies that this composition is
      regulated by temperature before, and during grain development. Understanding this
      regulation will be key to improving husk-to-caryopsis adhesion.

PMID- 29058625
TI  - The impact of patient advisors on healthcare outcomes: a systematic review.
AB  - BACKGROUND: Patient advisory councils are a way for healthcare organizations to
      promote patient engagement. Despite mandates to implement patient advisory
      councils through programs like the Patient-Centered Medical Home (PCMH), there is
      a paucity of data measuring the impact of patients functioning in advisory roles.
      Our objective is to investigate whether patient engagement in patient advisory
      councils is linked to improvements in clinical quality, patient safety or patient
      satisfaction. METHODS: We searched PubMed, SCOPUS, CINAHL and Google Scholar for
      English language publications between November 2002 to August 2015, using a
      combination of "patient advisor" and "care outcomes" search terms. Article
      selection utilized dual screening facilitated by DistillerSR software, with group
      discussion to resolve discordance. Observational studies, randomized controlled
      trials, and case studies were included that described patients serving in an
      advisory role where primary outcomes were mentioned. Reference lists of included
      studies and grey literature searches were conducted. Qualitative thematic
      analysis was performed to synthesize results. RESULTS: Database searching yielded
      639 articles total after removing duplicates, with 129 articles meeting full text
      inclusion criteria. 32 articles were identified for final review, 16 of which
      were case studies. Advisory roles included patient advisory councils, ad-hoc
      patient committees, community advisory councils, experience-based co-design, and
      other. Four practice-based studies from one research group, involving community
      advisors in the design of public health interventions, found improved clinical
      outcomes. No prospective experimental studies assessed the impact of patient
      advisors on patient safety or patient satisfaction. One cluster-randomized RCT
      showed that patient advisors helped health care planning efforts identify
      priorities more aligned with the PCMH. Ten case studies reported anecdotal
      benefit to individual patient advisors. CONCLUSION: Five included studies
      demonstrate promising methods for evaluating patient engagement in healthcare
      delivery and describe impacts on clinical outcomes and priority setting. Based on
      the case studies found, patient advisors tend to contribute to patient-facing
      services that may affect clinical care but are not easily evaluated. As clinics
      and hospitals implement patient advisory councils, rigorous evaluation of their
      programs is needed to support the expansion of system-level patient engagement.
      TRIAL REGISTRATION: This systematic review was registered in the PROSPERO
      database of the University of York Centre for Reviews and Dissemination (ID:
      2015: CRD42015030020 ).

PMID- 29058626
TI  - Combined platelet-rich plasma and lipofilling treatment provides great
      improvement in facial skin-induced lesion regeneration for scleroderma patients.
AB  - BACKGROUND: The use of stem cells, including mesenchymal stem cells (MSCs), for
      regenerative medicine is gaining interest for the clinical benefits so far
      obtained in patients. This study investigates the use of adipose autologous
      tissue in combination with platelet-rich plasma (PRP) to improve the clinical
      outcome of patients affected by systemic sclerosis (SSc). METHODS: Adipose
      derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy
      donors and SSc patients. The multilineage differentiation potential of AD-MSCs
      and their genotypic-phenotypic features were investigated. A cytokine production
      profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc
      patients. The adipose tissue-derived cell fraction, the so-called stromal
      vascular fraction (SVF), was coinjected with PRP in the perioral area of SSc
      patients. RESULTS: Histopathological and phenotypical analysis of adipose tissue
      from SSc patients revealed a disorganization of its distinct architecture coupled
      with an altered cell composition. Although AD-MSCs derived from SSc patients
      showed high multipotency, they failed to sustain a terminally differentiated
      progeny. Furthermore, SVFs derived from SSc patients differed from healthy donors
      in their MSC-like traits coupled with an aberrant cytokine production profile.
      Finally, the administration of PRP in combination with autologous SVF improved
      buccal's rhyme, skin elasticity and vascularization for all of the SSc patients
      enrolled in this study. CONCLUSIONS: This innovative regenerative therapy could
      be exploited for the treatment of chronic connective tissue diseases, including
      SSc.

PMID- 29058627
TI  - Urethrovaginal fistula following vaginal prolapse of a pedunculated uterine
      myoma: a case report.
AB  - BACKGROUND: Urethrovaginal fistulas are usually secondary to a foreign body in
      the vagina or to vaginal gynecologic surgeries. We present a case of an
      urethrovaginal fistula secondary to vaginal prolapse of a huge pedunculated
      submucosal uterine myoma. CASE PRESENTATION: A 25-year-old black African woman
      with a past history of huge uterine fibroids and an uncomplicated vaginal
      delivery 5 weeks prior to presentation consulted for a difficult micturition that
      occurred 2 days earlier. A vaginally prolapsed huge uterine myoma was diagnosed.
      The fibroid was easily twisted off per vagina. Around 9 days after prolapse of
      the fibroid or 5 days after its removal, she complained of a vaginal leaking of
      urine during micturition. An urethrovaginal fistula was diagnosed using a blue
      dye test. The fistula was successfully repaired with polyglactin and she was
      discharged on day 15. CONCLUSIONS: To the best of our knowledge, this is the
      first case of urethrovaginal fistula secondary to delivered uterine myoma. We
      recommend close postpartum follow-up of women carrying huge uterine fibroid and
      urgent management of a vaginally prolapsed uterine fibroid to reduce the risk of
      urethrovaginal fistula.

PMID- 29058629
TI  - 'I felt the world crash down on me': Women's experiences being denied legal
      abortion in Colombia.
AB  - BACKGROUND: In 2006, Colombia's constitutional court overturned a complete ban on
      abortion, liberalizing the procedure. Despite a relatively liberal new law, women
      still struggle to access safe and legal abortion services. We aimed to understand
      why women are denied services in Colombia, and what factors determine if and how
      they ultimately terminate pregnancies. METHODS: We recruited women denied
      abortion at a private facility in Bogota. Twenty-one participants completed an
      initial interview and eight completed a second longer interview. Two researchers
      documented themes and developed and applied a codebook to transcripts using
      ATLAS.ti. RESULTS: Participants faced barriers, such as lack of knowledge of
      service availability and delayed pregnancy recognition, leading to denial. Five
      out of eight participants ultimately received abortions in public hospitals, due
      to support from partners and a robust referral system; nevertheless, they
      received poor care. Those who continued pregnancies endured stigmatizing events
      and inaccurate medical counselling at referral facilities. Several women
      contemplated illegal abortion though were afraid to attempt it. CONCLUSION: We
      propose the following recommendations: 1) increase awareness about availability
      and legality of abortion services to prevent delay and consequent denial; 2)
      provide counseling and referral upon denial; and 3) train providers in
      interpersonal quality abortion care.

PMID- 29058628
TI  - Effect of strength training on sleep apnea severity in the elderly: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) occurs due to sleep-induced upper
      airway muscle relaxation resulting in increased pharyngeal collapsibility.
      Clinical trials have shown a favorable effect of exercise training on OSA
      severity in middle-aged adults. Aging is characterized by motor-unit loss. Force
      training may affect the whole body muscle tone. We hypothesize that interventions
      increasing muscle strength might propagate to motor units at the abductor
      pharyngeal muscles, reducing collapsibility and, hence, sleep apnea severity in
      elderly patients with obstructive sleep apnea. METHODS/DESIGN: This is a
      randomized clinical trial including patients between 65 and 80 years of age, with
      obstructive sleep apnea, and an apnea-hypopnea index (AHI) between 20 and 50
      events/hour, diagnosed by out-of-center in-home type III polysomnography. Forty
      subjects will be included and randomly assigned to two equal sized groups. The
      participants allocated to the intervention group will attend two sessions per
      week of one-hour strength training for the legs, arms, chest, back, and abdomen
      and the controls will receive advice on lifestyle change. The primary outcome
      measure of the study will be the change in apnea-hypopnea index and the secondary
      outcomes will be the body composition, evaluated by anthropometric and
      bioelectrical impedance variables; maximum dynamic force, appraised by one
      repetition maximum strength test; muscle quality and thickness by ultrasound;
      physical function assessed by sit-to-stand test, timed up and go test, handgrip
      strength test. The study duration will be 12 weeks. Intention-to-treat and per
      protocol analyses will be performed. DISCUSSION: The high prevalence of
      obstructive sleep apnea in elderly people is a public health issue. OSA is a
      recognized cause of cardiovascular disease and reduces quality of life due to
      sleepiness and fatigue. Exercise is a low-cost intervention that could help to
      detain the trend towards age-dependent loss of pharyngeal motor units and
      progressive severity of obstructive sleep apnea. Home-based strength exercises
      may represent a more practical approach than aerobic exercise for elderly
      patients. If the results confirm our hypothesis, further research on the clinical
      application of our findings will be warranted. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02742792 . Registered on 1 April 2016.

PMID- 29058630
TI  - Unsupervised gene expression analyses identify IPF-severity correlated
      signatures, associated genes and biomarkers.
AB  - BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a fatal fibrotic lung disease
      occurring predominantly in middle-aged and older adults. The traditional
      diagnostic classification of IPF is based on clinical, radiological, and
      histopathological features. However, the considerable heterogeneity in IPF
      presentation suggests that differences in gene expression profiles can help to
      characterize and distinguish disease severity. METHODS: We used data-driven
      unsupervised clustering analysis, combined with a knowledge-based approach to
      identify and characterize IPF subgroups. RESULTS: Using transcriptional profiles
      on lung tissue from 131 patients with IPF/UIP and 12 non-diseased controls, we
      identified six subgroups of IPF that generally correlated with the disease
      severity and lung function decline. Network-informed clustering identified the
      most severe subgroup of IPF that was enriched with genes regulating inflammatory
      processes, blood pressure and branching morphogenesis of the lung. The
      differentially expressed genes in six subgroups of IPF compared to healthy
      control include transcripts of extracellular matrix, epithelial-mesenchymal cell
      cross-talk, calcium ion homeostasis, and oxygen transport. Further, we compiled
      differentially expressed gene signatures to identify unique gene clusters that
      can segregate IPF from normal, and severe from mild IPF. Additional validations
      of these signatures were carried out in three independent cohorts of IPF/UIP.
      Finally, using knowledge-based approaches, we identified several novel candidate
      genes which may also serve as potential biomarkers of IPF. CONCLUSIONS: Discovery
      of unique and redundant gene signatures for subgroups in IPF can be greatly
      facilitated through unsupervised clustering. Findings derived from such gene
      signatures may provide insights into pathogenesis of IPF and facilitate the
      development of clinically useful biomarkers.

PMID- 29058633
TI  - Proper Utilization of Auxiliaries.

PMID- 29058631
TI  - Exercise and cancer-related fatigue in adults: a systematic review of previous
      systematic reviews with meta-analyses.
AB  - BACKGROUND: Conduct a systematic review of previous systematic reviews with meta
      analysis to determine the effects of exercise (aerobic, strength or both) on
      cancer-related-fatigue (CRF) in adults with any type of cancer. METHODS:
      Systematic reviews with meta-analyses of previous randomized controlled trials
      published through July of 2016 were included by searching six electronic
      databases and cross-referencing. Dual-selection and data abstraction were
      conducted. Methodological quality was assessed using the Assessment of Multiple
      Systematic Reviews (AMSTAR) instrument. Standardized mean differences (SMD) that
      were pooled using random-effects models were included as the effect size. In
      addition, 95% prediction intervals (PI), number needed-to-treat (NNT) and
      percentile improvements were calculated. RESULTS: Sixteen studies representing 2
      to 48 SMD effect sizes per analysis (mean +/- SD, 7 +/- 8, median = 5) and 37 to
      3254 participants (mean +/- SD, 633 +/- 690, median = 400) were included. Length
      of training lasted from 3 to 52 weeks (mean +/- SD, 14.6 +/- 3.1, median = 14),
      frequency from 1 to 10 times per week (mean +/- SD, 3.4 +/- 0.8, median = 3), and
      duration from 10 to 120 min per session (mean +/- SD, 44.3 +/- 5.5, median = 45).
      Adjusted AMSTAR scores ranged from 44.4% to 80.0% (mean +/- SD, 68.8% +/- 12.0%,
      median = 72.5%). Overall, mean SMD improvements in CRF ranged from -1.05 to 
      0.01, with 22 of 55 meta-analytic results (52.7%) statistically significant (non
      overlapping 95% CI). When PI were calculated for results with non-overlapping 95%
      CI, only 3 of 25 (12%) yielded non-overlapping 95% PI favoring reductions in CRF.
      Number needed-to-treat and percentile improvements ranged from 3 to 16 and 4.4 to
      26.4, respectively. CONCLUSIONS: A lack of certainty exists regarding the
      benefits of exercise on CRF in adults. However, exercise does not appear to
      increase CRF in adults. TRIAL REGISTRATION: PROSPERO Registration #
      CRD42016045405 .

PMID- 29058632
TI  - Implementation and effects of Movement-oriented Restorative Care in a nursing
      home - a quasi-experimental study.
AB  - BACKGROUND: The prevalence of dementia is expected to increase rapidly, and
      institutionalization is a common consequence of the disease. Dependence in
      activities of daily living (ADL) is a predictor for institutionalization and a
      determinant for the quality of life (QoL). A promising method to increase
      functional independence in nursing homes is a restorative care or function
      focused care (FFC) approach. Movement-oriented restorative care (MRC) is derived
      from the concept of FFC and restorative care and focuses on the integration of
      physical activity in the daily lives of nursing home residents with dementia
      using a multidisciplinary approach. The objective of this study was to assess the
      effectiveness of MRC in preservation of ADL independence and QoL in nursing home
      residents with dementia. METHODS: In this quasi-experimental 12-month study, the
      effects of MRC were compared to care as usual in 61 nursing home residents with
      moderate to severe dementia. The outcome measures were ADL independence and QoL.
      These outcomes were measured five times (i.e. at baseline, and after 3, 6, 9, and
      12 months). Additionally, data was collected regarding the degree of
      implementation, and the barriers to the implementation process. The effect of the
      intervention was analyzed using linear mixed model analyses. RESULTS: There was
      no significant overall intervention effect on ADL independence and QoL. A
      significant group-by-time interaction was found for the QoL subscale positive
      self-image: after a 12 month intervention period, the MRC group scored
      significantly better than the control group on positive self-image. Regarding the
      other subscales and the total score of the QoL, as well as ADL, no significant
      group-by-time interactions were found. CONCLUSIONS: MRC did not demonstrate
      significant improvements in ADL or QoL. After a 12-month intervention period,
      residents who received MRC showed higher scores on positive self-image compared
      to the control group. This study contributes to the limited research regarding
      the effect of MRC on resident outcomes. Further large-scale studies are
      recommended. TRIAL REGISTRATION: The trial was retrospectively registered in
      http://clinicaltrials.gov on February 2, 2017: NCT03001232 .

PMID- 29058634
TI  - Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal
      and experimental endotoxemic conditions.
AB  - BACKGROUND: Sugar-protein glycocalyx coats healthy endothelium, but its
      ultrastructure is not well described. Our aim was to determine the three
      dimensional ultrastructure of capillary endothelial glycocalyx in the heart,
      kidney, and liver, where capillaries are, respectively, continuous, fenestrated,
      and sinusoidal. METHODS: Tissue samples were processed with lanthanum-containing
      alkaline fixative, which preserves the structure of glycocalyx. RESULTS: Scanning
      and transmission electron microscopy revealed that the endothelial glycocalyx
      layer in continuous and fenestrated capillaries was substantially thicker than in
      sinusoids. In the heart, the endothelial glycocalyx presented as moss- or
      broccoli-like and covered the entire luminal endothelial cell surface. In the
      kidney, the glycocalyx appeared to nearly occlude the endothelial pores of the
      fenestrated capillaries and was also present on the surface of the renal
      podocytes. In sinusoids of the liver, glycocalyx covered not only the luminal
      side but also the opposite side, facing the space of Disse. In a mouse
      lipopolysaccharide-induced experimental endotoxemia model, the capillary
      endothelial glycocalyx was severely disrupted; that is, it appeared to be peeling
      off the cells and clumping. Serum concentrations of syndecan-1, a marker of
      glycocalyx damage, were significantly increased 24 h after administration of
      lipopolysaccharide. CONCLUSIONS: In the present study, we visualized the three
      dimensional ultrastructure of endothelial glycocalyx in healthy continuous,
      fenestrated, and sinusoidal capillaries, and we also showed their disruption
      under experimental endotoxemic conditions. The latter may provide a morphological
      basis for the microvascular endothelial dysfunction associated with septic injury
      to organs.

PMID- 29058635
TI  - Licit and illicit substance use patterns among university students in Germany
      using cluster analysis.
AB  - BACKGROUND: The use of multiple licit and illicit substances plays an important
      role in many university students' lives. Previous research on multiple substance
      use patterns of university students, however, often fails to examine use of
      different illicit substances and/or hookah. Our objective was to complement and
      advance the current knowledge about common consumption patterns regarding illicit
      substances and hookah use in this group. METHODS: Students from eight German
      universities completed an online survey as part of the INSIST study ('INternet
      based Social norms Intervention for the prevention of substance use among
      STudents') regarding their consumption of alcohol, tobacco, hookah, cannabis and
      other illicit substances. Cluster analysis identified distinct consumption
      patterns of concurrent and non-concurrent substance use and multinomial logistic
      regressions described key sociodemographic factors associated with these
      clusters. RESULTS: Six homogeneous groups were identified: 'Alcohol Abstainers'
      (10.8%), 'Drinkers Only' (48.2%), 'Drinkers and Cigarette Smokers' (14.6%),
      'Cannabis and Licit Substance Users' (11.2%), 'Hookah Users with Co-Use' (9.8%)
      and 'Illicit Substance Users with Co-Use' (5.4%). Illicit substance use clustered
      with the consumption of alcohol, tobacco and cannabis. Hookah use was regularly
      associated with alcohol consumption, less commonly associated with tobacco or
      cannabis use and very rarely associated with use of other illicit substances.
      Individuals consuming licit and illicit substances or hookah were mostly male and
      lived together with other students. Characteristics such as the number of years
      an individual had spent studying at a university, subject of study, immigrant
      background and religious affiliation were less commonly associated with cluster
      membership. CONCLUSIONS: Although we found substance use patterns in our sample
      largely similar to previous reports, we identified an important subgroup of
      individuals using both illicit and licit substances. These individuals may
      benefit especially from targeted interventions that focus on modifying addictive
      behavior patterns. TRIAL REGISTRATION: DRKS00007635 . Registered 17 December 2014
      (retrospectively registered).

PMID- 29058636
TI  - Clinical trials of CAR-T cells in China.
AB  - Novel immunotherapeutic agents targeting tumor-site microenvironment are
      revolutionizing cancer therapy. Chimeric antigen receptor (CAR)-engineered T
      cells are widely studied for cancer immunotherapy. CD19-specific CAR-T cells,
      tisagenlecleucel, have been recently approved for clinical application. Ongoing
      clinical trials are testing CAR designs directed at novel targets involved in
      hematological and solid malignancies. In addition to trials of single-target CAR
      T cells, simultaneous and sequential CAR-T cells are being studied for clinical
      applications. Multi-target CAR-engineered T cells are also entering clinical
      trials. T cell receptor-engineered CAR-T and universal CAR-T cells represent new
      frontiers in CAR-T cell development. In this study, we analyzed the
      characteristics of CAR constructs and registered clinical trials of CAR-T cells
      in China and provided a quick glimpse of the landscape of CAR-T studies in China.

PMID- 29058637
TI  - Exploring the clinically orientated roles of the general practice receptionist: a
      systematic review protocol.
AB  - BACKGROUND: The receptionist is the focal point of the practice, undertaking an
      array of clinically orientated roles such as triaging patients for GP
      consultations or managing repeat prescribing. However, the full nature and extent
      of the receptionist's clinical activities is unknown as are the implications for
      patients. The aim of the proposed review is to explore the nature of the
      receptionist's clinical roles, their extent and their implications for patients.
      In doing so, we will highlight any gaps in the evidence base which future
      research may explore. METHODS: The databases Medline/PubMed, Ovid, Cinahl, ASSIA,
      Cochrane, EMBASE and Science Direct will be searched for relevant literature. We
      will look at both qualitative and quantitative research on GP receptionists,
      based within primary care to explore their roles within the primary care team,
      the clinically relevant roles they undertake, the extent of these roles and any
      implications these roles might have. No limits are placed on the date or place of
      publication; however, only research published in English will be included.
      Screening, quality assessments and data extraction will be carried out by two
      reviewers, who are not blinded to study characteristics. Analysis follows a four
      stage method, established by Whittemore and Knafl (2005). DISCUSSION: The review
      will explore existing research covering the clinically orientated roles of the GP
      receptionist. The findings of the review will be important for healthcare
      professionals and academics working within primary healthcare. It will highlight
      and for the first time synthesise research relating to the complex and essential
      work of the GP receptionist. Our findings will inform the direction and focus of
      further research, as gaps in the knowledge base will be uncovered. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO registration no: CRD42016048957 .

PMID- 29058638
TI  - Use of social network analysis methods to study professional advice and
      performance among healthcare providers: a systematic review.
AB  - BACKGROUND: Social network analysis quantifies and visualizes relationships
      between and among individuals or organizations. Applications in the health sector
      remain underutilized. This systematic review seeks to analyze what social network
      methods have been used to study professional communication and performance among
      healthcare providers. METHODS: Ten databases were searched from 1990 through
      April 2016, yielding 5970 articles screened for inclusion by two independent
      reviewers who extracted data and critically appraised each study. Inclusion
      criteria were study of health care worker professional communication, network
      methods used, and patient outcomes measured. The search identified 10 systematic
      reviews. The final set of articles had their citations prospectively and
      retrospectively screened. We used narrative synthesis to summarize the findings.
      RESULTS: The six articles meeting our inclusion criteria described unique health
      sectors: one at primary healthcare level and five at tertiary level; five
      conducted in the USA, one in Australia. Four studies looked at multidisciplinary
      healthcare workers, while two focused on nurses. Two studies used mixed methods,
      four quantitative methods only, and one involved an experimental design. Four
      administered network surveys, one coded observations, and one used an existing
      survey to extract network data. Density and centrality were the most common
      network metrics although one study did not calculate any network properties and
      only visualized the network. Four studies involved tests of significance, and two
      used modeling methods. Social network analysis software preferences were evenly
      split between ORA and UCINET. All articles meeting our criteria were published in
      the past 5 years, suggesting that this remains in clinical care a nascent but
      emergent research area. There was marked diversity across all six studies in
      terms of research questions, health sector area, patient outcomes, and network
      analysis methods. CONCLUSION: Network methods are underutilized for the purposes
      of understanding professional communication and performance among healthcare
      providers. The paucity of articles meeting our search criteria, lack of studies
      in middle- and low-income contexts, limited number in non-tertiary settings, and
      few longitudinal, experimental designs, or network interventions present clear
      research gaps. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019328.

PMID- 29058639
TI  - Hospital acquired Acute Kidney Injury is associated with increased mortality but
      not increased readmission rates in a UK acute hospital.
AB  - BACKGROUND: Acute Kidney Injury (AKI) has evoked much interest over the past
      decade and is reported to be associated with high inpatient mortality.
      Preventable death and increased readmission rates related to AKI have been the
      focus of considerable interest. METHODS: We studied hospital acquired AKI in all
      emergency hospital admissions, except transfers from ICU to ICU or patients known
      to renal services, to ascertain mortality and readmission rates, and trackable
      modifiable factors for death, using cox regression and Kaplan Meier survival
      curves. Data was extracted from the electronic patient records and a series of
      case notes reviewed. Admissions were included between April 2006 and March 2010
      (and patients followed up until September 2011). RESULTS: Overall incidence of
      AKI was 2.2%, (AKI stage 1, 61%, stage 2,27% and stage 3, 12%). In patients who
      sustain in-hospital AKI, 34% die in hospital, 42% are dead at 90 days and 48% at
      1 year post discharge, compared to 12% 1 year mortality in patients without AKI.
      In multivariable analyses, AKI is an independent risk factor for in-hospital
      mortality (Hazard Ratio 1.6: 95% confidence intervals 1.43-1.75: P < 0.001),
      death within 90 days of discharge (Hazard Ratio 1.5: 95% confidence intervals 1.3
      1.9: P < 0.001) and subsequent mortality beyond 90 days (Hazard Ratio 2.9: 95%
      confidence intervals 2.7-3.1: P < 0.001) after adjustment for co-morbidities and
      peak C-reactive protein. Thirty percent of the patients who died in the first 90
      days post discharge and had AKI, also had malignancy. Readmission rates at 30 and
      90 days were not increased by AKI after adjustment for co-morbidities and peak C
      reactive protein. CONCLUSIONS: A significant proportion of deaths in the first 90
      days post-discharge may not be avoidable, due to malignancy and other end-stage
      disease. Readmission rates were not higher in patients who had had AKI.

PMID- 29058640
TI  - Implementation and dissemination of a transition of care program for rural
      veterans: a controlled before and after study.
AB  - BACKGROUND: Adapting promising health care interventions to local settings is a
      critical component in the dissemination and implementation process. The Veterans
      Health Administration (VHA) rural transitions nurse program (TNP) is a nurse-led,
      Veteran-centered intervention designed to improve transitional care for rural
      Veterans funded by VA national offices for dissemination to other VA sites
      serving a predominantly rural Veteran population. Here, we describe our novel
      approach to the implementation and evaluation = the TNP. METHODS: This is a
      controlled before and after study that assesses both implementation and
      intervention outcomes. During pre-implementation, we assessed site context using
      a mixed method approach with data from diverse sources including facility-level
      quantitative data, key informant and Veteran interviews, observations of the
      discharge process, and a group brainstorming activity. We used the Practical
      Robust Implementation and Sustainability Model (PRISM) to inform our inquiries,
      to integrate data from all sources, and to identify factors that may affect
      implementation. In the implementation phase, we will use internal and external
      facilitation, paired with audit and feedback, to encourage appropriate contextual
      adaptations. We will use a modified Stirman framework to document adaptations.
      During the evaluation phase, we will measure intervention and implementation
      outcomes at each site using the RE-AIM framework (Reach, Effectiveness, Adoption,
      Implementation, and Maintenance). We will conduct a difference-in-differences
      analysis with propensity-matched Veterans and VA facilities as a control. Our
      primary intervention outcome is 30-day readmission and Emergency Department visit
      rates. We will use our findings to develop an implementation toolkit that will
      inform the larger scale-up of the TNP across the VA. DISCUSSION: The use of PRISM
      to inform pre-implementation evaluation and synthesize data from multiple
      sources, coupled with internal and external facilitation, is a novel approach to
      engaging sites in adapting interventions while promoting fidelity to the
      intervention. Our application of PRISM to pre-implementation and midline
      evaluation, as well as documentation of adaptations, provides an opportunity to
      identify and address contextual factors that may impede or enhance implementation
      and sustainability of health interventions and inform dissemination.

PMID- 29058641
TI  - A systematic review protocol on the effectiveness of therapeutic exercises
      utilised by physiotherapists to improve function in patients with burns.
AB  - BACKGROUND: Therapeutic exercises play a crucial role in the management of burn
      injuries. The broad objective of this review is to systematically evaluate the
      effectiveness, safety and applicability to low-income countries of therapeutic
      exercises utilised by physiotherapists to improve function in patients with
      burns. Population = adults and children/adolescents with burns of any aspect of
      their bodies. Interventions = any aerobic and/or strength exercises delivered as
      part of a rehabilitation programme by anyone (e.g. physiotherapists, occupational
      therapists, nurses, doctors, community workers and patients themselves).
      Comparators = any comparator. Outcomes = any measure of outcome (e.g. quality of
      life, pain, muscle strength, range of movement, fear or quality of movement).
      Settings = any setting in any country. METHODS/DESIGN: A systematic review will
      be conducted by two blinded independent reviewers who will search articles on
      PubMed, CiNAHL, Cochrane library, Medline, Pedro, OTseeker, EMBASE, PsychINFO and
      EBSCOhost using predefined criteria. Studies of human participants of any age
      suffering from burns will be eligible, and there will be no restrictions on total
      body surface area. Only randomised controlled trials will be considered for this
      review, and the methodological quality of studies meeting the selection criteria
      will be evaluated using the Cochrane Collaboration tool for assessing risk of
      bias. The PRISMA reporting standards will be used to write the review. A
      narrative analysis of the findings will be done, but if pooling is possible, meta
      analysis will be considered. DISCUSSION: Burns may have a long-lasting impact on
      both psychological and physical functioning and thus it is important to identify
      and evaluate the effects of current and past aerobic and strength exercises on
      patients with burns. By identifying the characteristics of effective exercise
      programmes, guidelines can be suggested for developing intervention programmes
      aimed at improving the function of patients with burns. The safety and
      precautions of exercise regimes and the optimal frequency, duration, time and
      intensity will also be examined to inform further intervention. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CDR42016048370 .

PMID- 29058642
TI  - The effectiveness of universal parenting programmes: the CANparent trial.
AB  - BACKGROUND: There is substantial evidence for the efficacy and effectiveness of
      targeted parenting programmes but much less evidence regarding universal
      parenting programmes. The aim of the present study was to evaluate the
      effectiveness of the CANparent Trial of 12 universal parenting programmes, which
      were made available to parents of all children aged 0-6 years in three local
      authorities in England. To the best of our knowledge, this is the first study of
      universal parenting programmes on this scale. METHODS: Parents accessed a
      voucher, value L100, to attend an accredited programme of parenting classes.
      Parents completed measures of their mental well-being, parenting efficacy,
      parenting satisfaction, and parenting stress, at pre- and post-course.
      Comparative data were derived from a sample of non-participant parents in 16
      local authorities not providing CANparent programmes. A quasi-experimental design
      was adopted following estimation of propensity scores to balance the two groups
      on socio-demographic variables. RESULTS: Following their programme, changes in
      parenting stress were small and nonsignificant (Cohen's d frequency 0.07;
      intensity, 0.17). Participating parents showed significantly greater improvements
      than the comparison group for parenting efficacy (0.89) but not parenting
      satisfaction (-0.01). Mental well-being improved from 0.29 SD below the national
      norm to the national norm after the course. Parents were overwhelmingly positive
      about their course (88-94%) but this was lower for improvement in their
      relationship with their child (74%) and being a better parent (76%). CONCLUSIONS:
      The CANparent Trial demonstrated that universal parenting programmes can be
      effective in improving parents' sense of parenting efficacy and mental well-being
      when delivered to the full range of parents in community settings. However, there
      was no evidence of a reduction in levels of parenting stress; nor was there a
      significant improvement in satisfaction with being a parent. This is the first
      study of its kind in the UK; although the results point to a population benefit,
      more research is needed to determine whether benefits can be maintained in the
      longer term and whether they will translate into better parenting practices.

PMID- 29058643
TI  - The sibling sRNAs NgncR_162 and NgncR_163 of Neisseria gonorrhoeae participate in
      the expression control of metabolic, transport and regulatory proteins.
AB  - Neisseria gonorrhoeae is the causative agent of gonorrhoea, the second most
      common bacterial sexually transmitted disease. Riboregulation mediated by small
      regulatory RNAs (sRNAs) is increasingly recognized as an important means of gene
      expression control in this human-restricted pathogen. sRNAs act at the post
      transcriptional level by base-pairing with their target mRNAs which affects
      translation initiation and/or mRNA stability. In this study we initiated the
      characterization of a pair of highly conserved sRNAs of N. gonorrhoeae which
      exhibit redundant functions in the control of a common set of target genes. The
      identified targets of the sibling sRNAs NgncR_162 and NgncR_163 participate in
      basic metabolic processes including the methylcitrate and citrate cycle, aa
      uptake and degradation, and also in transcription regulation. Our data indicate
      that the sibling sRNAs control their targets via direct base-pairing between the
      same single-stranded domain(s) of the sRNA and the ribosome binding site in the
      5'-untranslated region of the mRNA.

PMID- 29058644
TI  - Undibacterium amnicola sp. nov., isolated from a freshwater stream.
AB  - Strain KYPY9T, isolated from the Funglin Stream in Taiwan, was characterized
      using a polyphasic taxonomy approach. Cells of KYPY9T were Gram-staining
      negative, strictly aerobic, motile by means of a single polar flagellum, rod
      shaped and formed light yellow colonies. Optimal growth occurred at 20-25 
      degrees C, at pH 7 and with 0 % NaCl. The results of phylogenetic analyses based
      on 16S rRNA gene sequences indicated that KYPY9T represented a member of the
      genus Undibacterium and the sequence similarity between the 16S rRNA genes of
      KYPY9T and of the type strains of other species of the genus Undibacterium ranged
      from 94.1 to 98.0 %. The closest relatives of KYPY9T were Undibacterium
      seohonense SHS5-24T (98.0 %) and Undibacterium macrobrachii CMJ-9T (97.0 %).
      KYPY9T had summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and C16 : 0 as
      the predominant fatty acids. The major cellular hydroxy fatty acid was C10 : 0 3
      OH. KYPY9T had phosphatidylethanolamine, phosphatidylglycerol and
      diphosphatidylglycerol as the predominant polar lipids. The polyamine profile was
      composed of the major compound 2-hydroxyputrescine and moderate amounts of
      putrescine. The major respiratory quinone was Q-8 and the DNA G+C content was
      47.4 mol%. The DNA-DNA relatedness of KYPY9T with respect to Undibacterium
      seohonense SHS5-24T and Undibacterium macrobrachii CMJ-9T was less than 35 %. On
      the basis of the phylogenetic inference and phenotypic data, KYPY9T was
      recognized as a representative of a novel species within the genus Undibacterium.
      The name Undibacterium amnicola sp. nov. is proposed, with KYPY9T (=BCRC
      81009T=LMG 29730T=KCTC 52442T) as the type strain.

PMID- 29058645
TI  - Two novel species of rapidly growing mycobacteria: Mycobacterium lehmannii sp.
      nov. and Mycobacterium neumannii sp. nov.
AB  - Two rapidly growing mycobacteria with identical 16S rRNA gene sequences were the
      subject of a polyphasic taxonomic study. The strains formed a well-supported
      subclade in the mycobacterial 16S rRNA gene tree and were most closely associated
      with the type strain of Mycobacterium novocastrense. Single and multilocus
      sequence analyses based on hsp65, rpoB and 16S rRNA gene sequences showed that
      strains SN 1900T and SN 1904T are phylogenetically distinct but share several
      chemotaxonomic and phenotypic features that are are consistent with their
      classification in the genus Mycobacterium. The two strains were distinguished by
      their different fatty acid and mycolic acid profiles, and by a combination of
      phenotypic features. The digital DNA-DNA hybridization (dDDH) and average
      nucleotide identity (ANI) values for strains SN 1900T and SN 1904T were 61.0 %
      and 94.7 %, respectively; in turn, the corresponding dDDH and ANI values with M.
      novocastrense DSM 44203T were 41.4 % and 42.8 % and 89.3 % and 89.5 %,
      respectively. These results show that strains SN1900T and SN 1904T form new
      centres of taxonomic variation within the genus Mycobacterium. Consequently,
      strains SN 1900T (40T=CECT 8763T=DSM 43219T) and SN 1904T (2409T=CECT 8766T=DSM
      43532T) are considered to represent novel species, for which the names
      Mycobacteriumlehmannii sp. nov. and Mycobacteriumneumannii sp. nov. are proposed.
      A strain designated as 'Mycobacteriumacapulsensis' was shown to be a bona fide
      member of the putative novel species, M. lehmannii.

PMID- 29058646
TI  - Vaccinia virus protein A49 activates Wnt signalling by targetting the E3 ligase
      beta-TrCP.
AB  - Vaccinia virus (VACV) encodes multiple proteins inhibiting the NF-kappaB
      signalling pathway. One of these, A49, targets the E3 ubiquitin ligase beta-TrCP,
      which is responsible for the ubiquitylation and consequential proteosomal
      degradation of IkappaBalpha and the release of the NF-kappaB heterodimer. beta
      TrCP is a pleiotropic enzyme ubiquitylating multiple cellular substrates,
      including the transcriptional activator beta-catenin. Here we demonstrate that
      A49 can activate the Wnt signalling pathway, a critical pathway that is involved
      in cell cycle and cell differentiation, and is controlled by beta-catenin. The
      data presented show that the expression of A49 ectopically or during VACV
      infection causes accumulation of beta-catenin, and that A49 triggering of Wnt
      signalling is dependent on binding beta-TrCP. This is consistent with A49
      blocking the ability of beta-TrCP to recognise beta-catenin and IkappaBalpha, and
      possibly other cellular targets. Thus, A49 targetting of beta-TrCP affects
      multiple cellular pathways, including the NF-kappaB and Wnt signalling cascades.

PMID- 29058647
TI  - Unravelling the transcriptional regulation of Saccharomyces cerevisiae UGA genes:
      the dual role of transcription factor Leu3.
AB  - Yeast cells can use gamma-aminobutyric acid (GABA), a non-protein amino acid, as
      a nitrogen source that is mainly imported by the permease Uga4 and catabolized by
      the enzymes GABA transaminase and succinate-semialdehyde dehydrogenase, encoded
      by the UGA1 and UGA2 genes, respectively. The three UGA genes are inducible by
      GABA and subject to nitrogen catabolite repression. Hence, their regulation
      occurs through two mechanisms, one dependent on the inducer and the other on
      nitrogen source quality. The aim of this work was to better understand the
      molecular mechanisms of transcription factors acting on different regulatory
      elements present in UGA promoters, such as Uga3, Dal81, Leu3 and the GATA
      factors, and to establish the mechanism of the concerted action between them. We
      found that Gat1 plays an important role in the induction of UGA4 transcription by
      GABA and that Gzf3 has an effect in cells grown in a poor nitrogen source such as
      proline and that this effect is positive on UGA4 expression. We also found that
      Gln3 and Dal80 affect the interaction of Uga3 and Dal81 on UGA promoters.
      Moreover, our results indicated that the repressing activity of Leu3 on UGA4 and
      UGA1 occurs through Dal80 since we demonstrated that Leu3 facilitates Dal80
      interaction with DNA. However, when the expression of GATA factors is null or
      negligible, Leu3 functions as an activator.

PMID- 29058648
TI  - Lactobacillus musae sp. nov., a novel lactic acid bacterium isolated from banana
      fruits.
AB  - Two Gram-stain-positive, catalase-negative, rod-shaped, bacterial strains (313T
      and 311) were isolated from banana fruits in Taiwan. Phylogenetic analysis based
      on 16S rRNA gene sequences revealed that the highest similarity to both strains
      corresponded to the type strain of Lactobacillus nantensis (99.19 %), followed by
      Lactobacillus crustorum (98.99 %), Lactobacillus heilongjiangensis (98.59 %) and
      Lactobacillus farciminis (98.52 %). Phylogenetic analysis based on the sequences
      of two housekeeping genes, pheS and rpoA, revealed that these two strains were
      well separated from the Lactobacillus reference strains. DNA-DNA relatedness
      values revealed genotype separation of the two strains from the above four
      species. The DNA G+C content of strain 313T was 35.5 mol%. The strains were
      homofermentative and mainly produced l-lactic acid from glucose. The major
      cellular fatty acids of strain 313T were 18 : 1omega6c and/or 18 : 1omega7c, 16 :
      0, and 19 : 1omega6c and/or 19 : 0 cyclo omega10c. Based on their physiological
      and genotypic characteristics, the isolates represent a novel species of the
      genus Lactobacillus, for which the name Lactobacillusmusae sp. nov. is proposed.
      The type strain is 313T=NBRC 112868T=BCRC 81020T).

PMID- 29058649
TI  - The emergence and evolution of influenza A (H1alpha) viruses in swine in Canada
      and the United States.
AB  - Swine are a key reservoir host for influenza A viruses (IAVs), with the potential
      to cause global pandemics in humans. Gaps in surveillance in many of the world's
      largest swine populations impede our understanding of how novel viruses emerge
      and expand their spatial range in pigs. Although US swine are intensively
      sampled, little is known about IAV diversity in Canada's population of ~12
      million pigs. By sequencing 168 viruses from multiple regions of Canada, our
      study reveals that IAV diversity has been underestimated in Canadian pigs for
      many years. Critically, a new H1 clade has emerged in Canada (H1alpha-3), with a
      two-amino acid deletion at H1 positions 146-147, that experienced rapid growth in
      Manitoba's swine herds during 2014-2015. H1alpha-3 viruses also exhibit a higher
      capacity to invade US swine herds, resulting in multiple recent introductions of
      the virus into the US Heartland following large-scale movements of pigs in this
      direction. From the Heartland, H1alpha-3 viruses have disseminated onward to both
      the east and west coasts of the United States, and may become established in
      Appalachia. These findings demonstrate how long-distance trading of live pigs
      facilitates the spread of IAVs, increasing viral genetic diversity and
      complicating pathogen control. The proliferation of novel H1alpha-3 viruses also
      highlights the need for expanded surveillance in a Canadian swine population that
      has long been overlooked, and may have implications for vaccine design.

PMID- 29058650
TI  - Significant spread of extensively drug-resistant Acinetobacter baumannii
      genotypes of clonal complex 92 among intensive care unit patients in a university
      hospital in southern Iran.
AB  - PURPOSE: Infections associated with Acinetobacter baumannii represent an
      increasing threat in healthcare settings. Therefore, we investigated the
      epidemiological relationship between clinical isolates of A. baumannii obtained
      from patients in a university hospital in Bandar Abbas in southern Iran.
      METHODOLOGY: Sixty-four consecutive non-duplicate clinical isolates collected
      during 2014-2015 were subjected to susceptibility testing, clonal relationship
      analysis using PFGE, multilocus variable-number tandem-repeat analysis (MLVA) and
      multilocus sequence typing (MLST), and examined for the presence of
      carbapenemases and integrons. RESULTS: Almost all A. baumannii isolates were
      extensively drug-resistant (XDR; 98 %) and carried an OXA carbapenemase gene
      (blaOXA-23-like; 98 %) and class 1 integrons (48 %). PFGE and MLST analysis
      identified three major genotypes, all belonging to clonal complex 92 (CC92):
      sequence type 848 (ST848) (n=23), ST451 (n=16) and ST195 (n=8). CC92 has
      previously been documented in the hospital setting in northern Iran, and ST195
      has been reported in Arab States of the Persian Gulf. These data suggest national
      and global transmission of A. baumannii CC92. CONCLUSION: This report
      demonstrates the occurrence and potential spread of closely related XDR genotypes
      of A. baumannii CC92 within a university hospital in southern Iran. These
      genotypes were found in the majority of the investigated isolates, showed high
      prevalence of blaOXA-23 and integron class 1, and were associated with stay in
      the intensive care unit. Very few treatment options remain for healthcare-adapted
      XDR A. baumannii, and hence effective measures are desperately needed to reduce
      the spread of these strains and resultant infections in the healthcare setting.

PMID- 29058651
TI  - Estimating chronic wasting disease susceptibility in cervids using real-time
      quaking-induced conversion.
AB  - In mammals, susceptibility to prion infection is primarily modulated by the
      host's cellular prion protein (PrPC) sequence. In the sheep scrapie model, a
      graded scale of susceptibility has been established both in vivo and in vitro
      based on PrPC amino acids 136, 154 and 171, leading to global breeding programmes
      to reduce the prevalence of scrapie in sheep. Chronic wasting disease (CWD)
      resistance in cervids is often characterized as decreased prevalence and/or
      protracted disease progression in individuals with specific alleles; at present,
      no PrPC allele conferring absolute resistance in cervids has been identified. To
      model the susceptibility of various naturally occurring and hypothetical cervid
      PrPC alleles in vitro, we compared the amplification rates and amyloid extension
      efficiencies of eight distinct CWD isolates in recombinant cervid PrPC substrates
      using real-time quaking-induced conversion. We hypothesized that the in vitro
      conversion characteristics of these isolates in cervid substrates would correlate
      to in vivo susceptibility - permitting susceptibility prediction for the rare
      alleles found in nature. We also predicted that hypothetical alleles with
      multiple resistance-associated codons would be more resistant to in vitro
      conversion than natural alleles with a single resistant codon. Our studies
      demonstrate that in vitro conversion metrics align with in vivo susceptibility,
      and that alleles with multiple amino acid substitutions, each influencing
      resistance independently, do not necessarily contribute additively to conversion
      resistance. Importantly, we found that the naturally occurring whitetail deer
      QGAK substrate exhibited the slowest amplification rate among those evaluated,
      suggesting that further investigation of this allele and its resistance in vivo
      is warranted.

PMID- 29058652
TI  - VerZ, a Zn(II)2Cys6 DNA-binding protein, regulates the biosynthesis of
      verticillin in Clonostachys rogersoniana.
AB  - Verticillins are the dimeric epipolythiodioxopiperazines (ETPs) produced by the
      fungus Clonostachys rogersoniana. Despite their profound biological effects, they
      are commonly produced in rice medium as complex mixtures that are difficult to
      separate, limiting further study and evaluation for this class of metabolites.
      Therefore, there is an urgent need to understand the regulation of verticillin
      biosynthesis. Recently, we cloned the biosynthetic gene cluster of verticillin
      (ver), and identified the only regulatory gene verZ in this cluster. The deduced
      product of verZ contains a basic Zn(II)2Cys6 DNA-binding domain. Disruption of
      verZ significantly reduced the production of 11'-deoxyverticillin A (C42) and
      decreased the transcriptional level of the verticillin biosynthetic genes. To
      further reveal its function, a recombinant gene encoding the DNA-binding domain
      of VerZ was expressed in E. coli and the His6-tagged VerZbd was purified to
      homogeneity by Ni-NTA chromatography. Electrophoretic mobility shift assays
      (EMSAs) showed that VerZbd bound specifically to the promoter regions of the
      verticillin biosynthetic genes. Bioinformatic analysis of the VerZbd-binding
      regions revealed a conserved palindromic sequence of
      (T/C)(C/A)(G/T)GN3CC(G/T)(A/G)(G/C). Base substitution of the conserved sequence
      completely abolished the binding activity of VerZbd to its targets. These results
      suggested that VerZ controls verticillin production through directly activating
      transcription of the biosynthetic genes in C. rogersoniana.

PMID- 29058653
TI  - Spirosoma koreense sp. nov., a species of the family Cytophagaceae isolated from
      beach soil.
AB  - A Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, aerobic
      bacterium, designated 15J8-5T, was isolated from beach soil on Jeju Island,
      Republic of Korea. The isolate grew at 10-37  degrees C (optimal 25  degrees C),
      pH 6-8 (optimal pH 7) and in the presence of 0-1 % (w/v) NaCl. The results of
      comparative 16S rRNA gene sequence analysis indicated that strain 15J8-5T
      represented a member of the family Cytophagaceae, phylum Bacteroidetes and was
      most closely related to Spirosoma knui 15J8-12T (93.1 % similarity), Spirosoma
      spitsbergense SPM-9T (93.1 %) and Spirosoma endophyticum EX36T (93.1 %). The G+C
      content of the genomic DNA of the novel strain was 48.0 mol%. The isolate
      contained menaquinone MK-7 as the predominant respiratory quinone,
      phosphatidylethanolamine as the major polar lipid, and summed feature 3 (C16 :
      1omega7c/C16 : 1omega6c; 32.8 %), C16 : 1omega5c (24.8 %) and C16 : 0 (11.7 %) as
      the major fatty acids, which supported the affiliation of strain 15J8-5T to the
      genus Spirosoma. The results of physiological and biochemical tests allowed
      genotypic and phenotypic differentiation of strain 15J8-5T from members of the
      genus Spirosoma. Based on its phenotypic properties and phylogenetic
      distinctiveness, strain 15J8-5T represents a novel species of the genus
      Spirosoma, for which the name Spirosomakoreense sp. nov. is proposed. The type
      strain is 15J8-5T (=KCTC 52027T=JCM 31992T).

PMID- 29058654
TI  - Exogenous polyunsaturated fatty acids (PUFAs) alter phospholipid composition,
      membrane permeability, biofilm formation and motility in Acinetobacter baumannii.
AB  - Acinetobacter baumannii is a ubiquitous multidrug-resistant bacteria that is
      found on a variety of surfaces, including skin, hair and soil. During the past
      decade, A. baumannii has emerged as a significant cause of nosocomial infections
      in the United States. Recent studies have highlighted the ability of some
      bacteria to utilize a wide variety of fatty acids as a membrane remodelling
      strategy. Considering this, we hypothesized that fatty acids may have an effect
      on the emerging pathogen A. baumannii. Thin-layer chromatography indicated
      structural alterations to major phospholipids. Liquid chromatography/mass
      spectrometry confirmed the assimilation of numerous exogenous polyunsaturated
      fatty acids (PUFAs) into the phospholipid species of A. baumannii. The
      incorporation of fatty acids affected several bacterial phenotypes, including
      membrane permeability, biofilm formation, surface motility and antimicrobial
      peptide resistance.

PMID- 29058655
TI  - The discovery of Halictivirus resolves the Sinaivirus phylogeny.
AB  - By providing pollination services, bees are among the most important insects,
      both in ecological and economical terms. Combined next-generation and classical
      sequencing approaches were applied to discover and study new insect viruses
      potentially harmful to bees. A bioinformatics virus discovery pipeline was used
      on individual Illumina transcriptomes of 13 wild bees from three species from the
      genus Halictus and 30 ants from six species of the genera Messor and
      Aphaenogaster. This allowed the discovery and description of three sequences of a
      new virus termed Halictus scabiosae Adlikon virus (HsAV). Phylogenetic analyses
      of ORF1, RNA-dependent RNA-polymerase (RdRp) and capsid genes showed that HsAV is
      closely related to (+)ssRNA viruses of the unassigned Sinaivirus genus but
      distant enough to belong to a different new genus we called Halictivirus. In
      addition, our study of ant transcriptomes revealed the first four sinaivirus
      sequences from ants (Messor barbarus, M. capitatus and M. concolor). Maximum
      likelihood phylogenetic analyses were performed on a 594 nt fragment of the
      ORF1/RdRp region from 84 sinaivirus sequences, including 31 new Lake Sinai
      viruses (LSVs) from honey bees collected in five countries across the globe and
      the four ant viral sequences. The phylogeny revealed four main clades potentially
      representing different viral species infecting honey bees. Moreover, the ant
      viruses belonged to the LSV4 clade, suggesting a possible cross-species
      transmission between bees and ants. Lastly, wide honey bee screening showed that
      all four LSV clades have worldwide distributions with no obvious geographical
      segregation.

PMID- 29058656
TI  - Bursal transcriptome profiling of different inbred chicken lines reveals key
      differentially expressed genes at 3 days post-infection with very virulent
      infectious bursal disease virus.
AB  - Infectious bursal disease is a highly contagious disease in the poultry industry
      and causes immunosuppression in chickens. Genome-wide regulations of immune
      response genes of inbred chickens with different genetic backgrounds, following
      very virulent infectious bursal disease virus (vvIBDV) infection are poorly
      characterized. Therefore, this study aims to analyse the bursal tissue
      transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following
      infection with vvIBDV strain UK661 using strand-specific next-generation
      sequencing, by highlighting important genes and pathways involved in the infected
      chicken during peak infection at 3 days post-infection. All infected chickens
      succumbed to the infection without major variations among the different lines.
      However, based on the viral loads and bursal lesion scoring, lines P and 6 can be
      considered as the most susceptible lines, while lines 15 and N were regarded as
      the least affected lines. Transcriptome profiling of the bursa identified 4588
      genes to be differentially expressed, with 2985 upregulated and 1642
      downregulated genes, in which these genes were commonly or uniquely detected in
      all or several infected lines. Genes that were upregulated are primarily pro
      inflammatory cytokines, chemokines and IFN-related. Various genes that are
      associated with B-cell functions and genes related to apoptosis were
      downregulated, together with the genes involved in p53 signalling. In conclusion,
      bursal transcriptome profiles of different inbred lines showed differential
      expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT
      signalling genes, MAPK signalling genes, and their related pathways following
      vvIBDV infection.

PMID- 29058657
TI  - Nitrogen regulator GlnR directly controls transcription of genes encoding lysine
      deacetylases in Actinobacteria.
AB  - N-Lysine acetylation is a dynamic, reversible and regulatory post-translational
      modification (PTM) in prokaryotes, which integrates and coordinates metabolisms
      responding to environmental clues. However, the molecular mechanism underlying
      the signalling pathway from nutrient sensing to protein acetylation remains
      incompletely understood in micro-organisms. Here we found that global nitrogen
      regulator GlnR directly controls transcription of genes encoding lysine
      deacetylases in Actinobacteria. Electrophoretic mobility shift assays and real
      time PCR (RT-PCR) in three Actinobacteria species (Saccharopolyspora erythraea,
      Streptomyces coelicolor and Mycobacterium smegmatis) revealed that GlnR regulator
      protein is able to interact with the promoter regions of these genes and activate
      their transcription. Furthermore, it was demonstrated that cellular acetylation
      status (acetylome) is modulated by extracellular nitrogen availability. Our
      results present an example of the novel complete signal transduction mechanism of
      regulating protein deacetylation through a nutrient-sensing pleiotropic regulator
      in response to nutrient availability.

PMID- 29058658
TI  - Winogradskyella haliclonae sp. nov., isolated from a marine sponge of the genus
      Haliclona.
AB  - A yellow-pigmented, Gram-stain-negative, motile and rod-shaped bacterium, strain
      M1A16T, was isolated from the internal tissue of a sponge of the genus Haliclona,
      which was long-term cultured in the CEMarin aquaria system at Justus Liebig
      University of Giessen. The strain grew well at 20-32  degrees C (optimum 25 
      degrees C), in the presence of 0-6 % NaCl (optimum 3 %), and at pH 5.5-9.0
      (optimum pH 7.0-8.0). Phylogenetic analysis based on its 16S rRNA gene sequence
      placed the strain within the monophyletic cluster of the genus Winogradskyella
      with highest sequence similarity to Winogradskyella jejuensis CP32T (98.3 % 16S
      rRNA gene sequence similarity). Sequence similarities to all other type strains
      were 98.0 % or less. DNA-DNA hybridization of strain M1A16T with W. jejuensis
      CP32T resulted in hybridization values of 44.1 % (reciprocal 68.1 %). Major
      cellular fatty acids of strain M1A16T were iso-C15 : 1 G (18.1 %), iso-C15 : 0
      (13.7 %), C16 : 1omega7c (12.9 %), iso-C17 : 0 3-OH (10.6 %) and iso-C16 : 0 3-OH
      (10.2 %). The overall polyamine content was very low with major components being
      cadaverine, spermidine and sym-homospermidine. The major quinone was menaquinone
      MK-6. The polar lipid profile contained predominantly phosphatidylethanolamine,
      two unidentified aminolipids and two unidentified lipids devoid of a detectable
      functional group. The genomic DNA G+C content was 32.7 mol%. Based on the
      phylogenetic, chemotaxonomic and phenotypic analyses, strain M1A16T represents a
      novel species of the genus Winogradskyella, for which the name Winogradskyella
      haliclonae sp. nov. is proposed. The type strain is M1A16T (=DSM 103138T=CCM
      8681T=LMG 29588T=CIP 111091T).

PMID- 29058659
TI  - Spirosoma litoris sp. nov., a bacterium isolated from beach soil.
AB  - A Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, aerobic
      bacterium, designated 15J16-2T3AT, was isolated from beach soil on Jeju Island,
      South Korea. Strain 15J16-2T3AT grew at 10-37  degrees C (optimum growth at 25 
      degrees C) and pH 6.5-8.5 (optimum growth at pH 7). Based on 16S rRNA gene
      phylogenetic analysis, the novel strain was closely related to members of the
      genus Spirosoma(94.8-89.9 % similarities) and formed a separate branch within the
      genus together with Spirosoma luteolum 16F6ET in neighbour-joining, maximum
      likelihood and maximum-parsimony phylogenetic trees. The G+C content of the
      genomic DNA of strain 15J16-2T3AT was 47.6 mol%. The detection of menaquinone MK
      7 as the predominant respiratory quinone, a fatty acid profile with summed
      feature 3 (C16 : 1omega7c/C16 : 1omega6c; 35.5 %), C16 : 1omega5c (26.6 %), and
      iso C15 : 0 (10.1 %) as the major components, phosphatidylethanolamine and
      unidentified aminophospholipid as the major polar lipids also support the
      affiliation of strain 15J16-2T3AT with the genus Spirosoma. The results of
      physiological and biochemical tests allowed genotypic and phenotypic
      differentiation of strain 15J16-2T3AT from members the genus Spirosoma. On the
      basis of its phenotypic properties and phylogenetic distinctiveness, strain 15J16
      2T3AT represents a novel species of the genus Spirosoma, for which the name
      Spirosoma litoris sp. nov. is proposed. The type strain is 15J16-2T3AT (=KCTC
      52029T=JCM 31999T).

PMID- 29058660
TI  - Soonwooa purpurea sp. nov., isolated from a fresh water river.
AB  - A pale-brown-coloured, rod-shaped, non-motile, and Gram-reaction-negative
      bacterium, strain I54T, was isolated from a water sample of a freshwater river in
      Iksan, Republic of Korea. The phylogenetic affiliation based on 16S rRNA gene
      sequence analysis showed that strain I54T belonged to the genus Soonwooa of the
      family Flavobacteriaceae with a sequence similarity of 97.5 % to Soonwooa
      buanensis HM0024T. The major fatty acids (>5 %) of strain I54T were iso-C15 : 0,
      anteiso-C15 : 0, summed feature 3 (C16 : 1omega7c/C16 : 1omega6c) and iso-C17 : 0
      3-OH. Phosphatidylethanolamine, one aminolipid and two unknown lipids were the
      major polar lipids. The G+C content of the genomic DNA was 34.2 (+/-0.3)mol% and
      MK6 was the sole respiratory quinone. On the basis of its molecular and
      phenotypic characteristics, strain I54T represents a novel species in the genus
      Soonwooa, for which the name Soonwooapurpurea sp. nov. is proposed. The type
      strain is I54T (=KCTC 52722T=JCM 31880T).

PMID- 29058661
TI  - The cellular endosomal protein stannin inhibits intracellular trafficking of
      human papillomavirus during virus entry.
AB  - Human papillomaviruses (HPVs) are the most common sexually transmitted viruses
      and one of the most important infectious causes of cancers worldwide. While
      prophylactic vaccines are effective against certain strains of HPV, established
      infections still cause deadly cancers in both men and women. HPV traffics to the
      nucleus via the retrograde transport pathway, but the mechanism of intracellular
      transport of non-enveloped viruses such as HPV is incompletely understood. Using
      an overexpression screen, we identify several genes that control HPV16 entry. We
      focused on the mechanism by which one of the screen hits, stannin, blocks HPV16
      infection. Stannin has not been previously implicated in virus entry.
      Overexpression of stannin specifically inhibits infection by several HPV types,
      but not other viruses tested. Stannin is constitutively expressed in human
      keratinocytes, and its basal levels limit entry by HPV16. Stannin is localized to
      the endolysosomal compartment and does not affect HPV16 binding to cells, virus
      uptake, or virus uncoating, but inhibits the entry of HPV into the trans-Golgi
      network (TGN) and stimulates HPV degradation. We further show that stannin
      interacts with L1 major capsid protein and impairs the interaction of the L2
      minor capsid protein with retromer, which is required for virus trafficking to
      the TGN. Our findings shed light on a novel cellular protein that interferes with
      HPV entry and highlight the role of retrograde transport in HPV entry.

PMID- 29058662
TI  - Spirosoma flavum sp. nov., isolated from Arctic tundra soil.
AB  - A yellow-pigmented strain, designated Y4AR-5T, was characterized by using a
      polyphasic approach. The strain was isolated from a tundra soil from near
      Longyearbyen, Svalbard Islands, Norway. The cells were Gram-stain-negative,
      aerobic, rod-shaped and non-motile. Growth occurred at 4-28  degrees C (optimum
      20  degrees C) and pH 6.0-9.0 (optimum pH 8.0) and with 0-0.5 % (w/v) NaCl
      (optimum 0 %). The major respiratory quinone was MK-7. The polar lipids were
      phosphatidylethanolamine (PE), an aminophospholipid (APL), a phospholipid (PL),
      an unidentified aminolipid (AL) and two unidentified lipids. The results of
      analysis of the 16S rRNA gene indicated that the novel strain was most closely
      related to members of the genus Spirosoma (96.2 % sequence similarity with
      Spirosoma endophyticum). The genomic DNA G+C content was 45.9 mol%. The major
      cellular fatty acids were summed feature 3 (C16 : 1omega7c and/or C16 :
      1omega6c), C16 : 1omega5c, iso-C17 : 0 3-OH and iso-C15 : 0. On the basis of its
      phenotypic and genotypic properties, strain Y4AR-5T should be classified as
      representing a novel species of the genus Spirosoma, for which the name
      Spirosomaflavum sp. nov. is proposed. The type strain is Y4AR-5T (=CCTCC AB
      2015352T=KCTC 52490T).

PMID- 29058663
TI  - Yellow Fever Virus RNA in Urine and Semen of Convalescent Patient, Brazil.
AB  - Yellow fever virus RNA is usually detected in blood of infected humans. We
      detected virus RNA in urine and semen samples from a convalescent patient. A
      complete virus genome was sequenced for an isolate from a urine sample. This
      virus had a South American I genotype and unique synapomorphic changes.

PMID- 29058664
TI  - Expected Duration of Adverse Pregnancy Outcomes after Zika Epidemic.
AB  - Evidence is increasing that Zika virus-related adverse outcomes can occur
      throughout pregnancy. Mathematical modeling analysis using reported outcome data
      suggests that surveillance for these outcomes should begin as soon as an outbreak
      is detected and should continue for 40 weeks after the outbreak ends.

PMID- 29058665
TI  - Real-time modelling of a pandemic influenza outbreak.
AB  - BACKGROUND: Real-time modelling is an essential component of the public health
      response to an outbreak of pandemic influenza in the UK. A model for epidemic
      reconstruction based on realistic epidemic surveillance data has been developed,
      but this model needs enhancing to provide spatially disaggregated epidemic
      estimates while ensuring that real-time implementation is feasible. OBJECTIVES:
      To advance state-of-the-art real-time pandemic modelling by (1) developing an
      existing epidemic model to capture spatial variation in transmission, (2)
      devising efficient computational algorithms for the provision of timely
      statistical analysis and (3) incorporating the above into freely available
      software. METHODS: Markov chain Monte Carlo (MCMC) sampling was used to derive
      Bayesian statistical inference using 2009 pandemic data from two candidate
      modelling approaches: (1) a parallel-region (PR) approach, splitting the pandemic
      into non-interacting epidemics occurring in spatially disjoint regions; and (2) a
      meta-region (MR) approach, treating the country as a single meta-population with
      long-range contact rates informed by census data on commuting. Model
      discrimination is performed through posterior mean deviance statistics alongside
      more practical considerations. In a real-time context, the use of sequential
      Monte Carlo (SMC) algorithms to carry out real-time analyses is investigated as
      an alternative to MCMC using simulated data designed to sternly test both
      algorithms. SMC-derived analyses are compared with 'gold-standard' MCMC-derived
      inferences in terms of estimation quality and computational burden. RESULTS: The
      PR approach provides a better and more timely fit to the epidemic data. Estimates
      of pandemic quantities of interest are consistent across approaches and, in the
      PR approach, across regions (e.g. R0 is consistently estimated to be 1.76-1.80,
      dropping by 43-50% during an over-summer school holiday). A SMC approach was
      developed, which required some tailoring to tackle a sudden 'shock' in the data
      resulting from a pandemic intervention. This semi-automated SMC algorithm
      outperforms MCMC, in terms of both precision of estimates and their timely
      provision. Software implementing all findings has been developed and installed
      within Public Health England (PHE), with key staff trained in its use.
      LIMITATIONS: The PR model lacks the predictive power to forecast the spread of
      infection in the early stages of a pandemic, whereas the MR model may be limited
      by its dependence on commuting data to describe transmission routes. As demand
      for resources increases in a severe pandemic, data from general practices and on
      hospitalisations may become unreliable or biased. The SMC algorithm developed is
      semi-automated; therefore, some statistical literacy is required to achieve
      optimal performance. CONCLUSIONS: Following the objectives, this study found that
      timely, spatially disaggregate, real-time pandemic inference is feasible, and a
      system that assumes data as per pandemic preparedness plans has been developed
      for rapid implementation. FUTURE WORK RECOMMENDATIONS: Modelling studies
      investigating the impact of pandemic interventions (e.g. vaccination and school
      closure); the utility of alternative data sources (e.g. internet searches) to
      augment traditional surveillance; and the correct handling of test sensitivity
      and specificity in serological data, propagating this uncertainty into the real
      time modelling. TRIAL REGISTRATION: Current Controlled Trials ISRCTN40334843.
      FUNDING: This project was funded by the National Institute for Health Research
      (NIHR) Health Technology programme and will be published in full in Health
      Technology Assessment; Vol. 21, No. 58. See the NIHR Journals Library website for
      further project information. Daniela De Angelis was supported by the UK Medical
      Research Council (Unit Programme Number U105260566) and by PHE. She received
      funding under the NIHR grant for 10% of her time. The rest of her salary was
      provided by the MRC and PHE jointly.

PMID- 29058666
TI  - COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin
      sorting signal.
AB  - The COPI coat forms transport vesicles from the Golgi complex and plays a poorly
      defined role in endocytic trafficking. Here we show that COPI binds K63-linked
      polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated
      yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles
      with the plasma membrane, and then recycles through the endocytic pathway to the
      Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a
      beta'-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts
      Snc1 recycling causing aberrant accumulation in internal compartments. Moreover,
      replacement of the beta'-COP propeller domain with unrelated ubiquitin-binding
      domains restores Snc1 recycling. These results indicate that ubiquitination, a
      modification well known to target membrane proteins to the lysosome or vacuole
      for degradation, can also function as recycling signal to sort a SNARE into COPI
      vesicles in a non-degradative pathway.

PMID- 29058667
TI  - Control of plant cell fate transitions by transcriptional and hormonal signals.
AB  - Plant meristems carry pools of continuously active stem cells, whose activity is
      controlled by developmental and environmental signals. After stem cell division,
      daughter cells that exit the stem cell domain acquire transit amplifying cell
      identity before they are incorporated into organs and differentiate. In this
      study, we used an integrated approach to elucidate the role of HECATE (HEC) genes
      in regulating developmental trajectories of shoot stem cells in Arabidopsis
      thaliana. Our work reveals that HEC function stabilizes cell fate in distinct
      zones of the shoot meristem thereby controlling the spatio-temporal dynamics of
      stem cell differentiation. Importantly, this activity is concomitant with the
      local modulation of cellular responses to cytokinin and auxin, two key
      phytohormones regulating cell behaviour. Mechanistically, we show that HEC
      factors transcriptionally control and physically interact with MONOPTEROS (MP), a
      key regulator of auxin signalling, and modulate the autocatalytic stabilization
      of auxin signalling output.

PMID- 29058668
TI  - E3 ubiquitin ligase Bre1 couples sister chromatid cohesion establishment to DNA
      replication in Saccharomyces cerevisiae.
AB  - Bre1, a conserved E3 ubiquitin ligase in Saccharomyces cerevisiae, together with
      its interacting partner Lge1, are responsible for histone H2B monoubiquitination,
      which regulates transcription, DNA replication, and DNA damage response and
      repair, ensuring the structural integrity of the genome. Deletion of BRE1 or LGE1
      also results in whole chromosome instability. We discovered a novel role for
      Bre1, Lge1 and H2Bub1 in chromosome segregation and sister chromatid cohesion.
      Bre1's function in G1 and S phases contributes to cohesion establishment, but it
      is not required for cohesion maintenance in G2 phase. Bre1 is dispensable for the
      loading of cohesin complex to chromatin in G1, but regulates the localization of
      replication factor Mcm10 and cohesion establishment factors Ctf4, Ctf18 and Eco1
      to early replication origins in G1 and S phases, and promotes cohesin subunit
      Smc3 acetylation for cohesion stabilization. H2Bub1 epigenetically marks the
      origins, potentially signaling the coupling of DNA replication and cohesion
      establishment.

PMID- 29058669
TI  - CRISPRi is not strand-specific at all loci and redefines the transcriptional
      landscape.
AB  - CRISPRi, an adapted CRISPR-Cas9 system, is proposed to act as a strand-specific
      roadblock to repress transcription in eukaryotic cells using guide RNAs (sgRNAs)
      to target catalytically inactive Cas9 (dCas9) and offers an alternative to
      genetic interventions for studying pervasive antisense transcription. Here, we
      successfully use click chemistry to construct DNA templates for sgRNA expression
      and show, rather than acting simply as a roadblock, sgRNA/dCas9 binding creates
      an environment that is permissive for transcription initiation/termination, thus
      generating novel sense and antisense transcripts. At HMS2 in Saccharomyces
      cerevisiae, sgRNA/dCas9 targeting to the non-template strand for antisense
      transcription results in antisense transcription termination, premature
      termination of a proportion of sense transcripts and initiation of a novel
      antisense transcript downstream of the sgRNA/dCas9-binding site. This
      redefinition of the transcriptional landscape by CRISPRi demonstrates that it is
      not strand-specific and highlights the controls and locus understanding required
      to properly interpret results from CRISPRi interventions.

PMID- 29058670
TI  - Action history influences subsequent movement via two distinct processes.
AB  - The characteristics of goal-directed actions tend to resemble those of previously
      executed actions, but it is unclear whether such effects depend strictly on
      action history, or also reflect context-dependent processes related to predictive
      motor planning. Here we manipulated the time available to initiate movements
      after a target was specified, and studied the effects of predictable movement
      sequences, to systematically dissociate effects of the most recently executed
      movement from the movement required next. We found that directional biases due to
      recent movement history strongly depend upon movement preparation time,
      suggesting an important contribution from predictive planning. However predictive
      biases co-exist with an independent source of bias that depends only on recent
      movement history. The results indicate that past experience influences movement
      execution through a combination of temporally-stable processes that are strictly
      use-dependent, and dynamically-evolving and context-dependent processes that
      reflect prediction of future actions.

PMID- 29058671
TI  - Preferential assembly of heteromeric kainate and AMPA receptor amino terminal
      domains.
AB  - Ion conductivity and the gating characteristics of tetrameric glutamate receptor
      ion channels are determined by their subunit composition. Competitive homo- and
      hetero-dimerization of their amino-terminal domains (ATDs) is a key step
      controlling assembly. Here we measured systematically the thermodynamic
      stabilities of homodimers and heterodimers of kainate and AMPA receptors using
      fluorescence-detected sedimentation velocity analytical ultracentrifugation.
      Measured affinities span many orders of magnitude, and complexes show large
      differences in kinetic stabilities. The association of kainate receptor ATD
      dimers is generally weaker than the association of AMPA receptor ATD dimers, but
      both show a general pattern of increased heterodimer stability as compared to the
      homodimers of their constituents, matching well physiologically observed receptor
      combinations. The free energy maps of AMPA and kainate receptor ATD dimers
      provide a framework for the interpretation of observed receptor subtype
      combinations and possible assembly pathways.

PMID- 29058672
TI  - A corticostriatal deficit promotes temporal distortion of automatic action in
      ageing.
AB  - The acquisition of motor skills involves implementing action sequences that
      increase task efficiency while reducing cognitive loads. This learning capacity
      depends on specific cortico-basal ganglia circuits that are affected by normal
      ageing. Here, combining a series of novel behavioural tasks with extensive
      neuronal mapping and targeted cell manipulations in mice, we explored how ageing
      of cortico-basal ganglia networks alters the microstructure of action throughout
      sequence learning. We found that, after extended training, aged mice produced
      shorter actions and displayed squeezed automatic behaviours characterised by
      ultrafast oligomeric action chunks that correlated with deficient reorganisation
      of corticostriatal activity. Chemogenetic disruption of a striatal subcircuit in
      young mice reproduced age-related within-sequence features, and the introduction
      of an action-related feedback cue temporarily restored normal sequence structure
      in aged mice. Our results reveal static properties of aged cortico-basal ganglia
      networks that introduce temporal limits to action automaticity, something that
      can compromise procedural learning in ageing.

PMID- 29058673
TI  - Risk of punishment influences discrete and coordinated encoding of reward-guided
      actions by prefrontal cortex and VTA neurons.
AB  - Actions motivated by rewards are often associated with risk of punishment. Little
      is known about the neural representation of punishment risk during reward-seeking
      behavior. We modeled this circumstance in rats by designing a task where actions
      were consistently rewarded but probabilistically punished. Spike activity and
      local field potentials were recorded during task performance simultaneously from
      VTA and mPFC, two reciprocally connected regions implicated in reward-seeking and
      aversive behaviors. At the single unit level, we found that ensembles of putative
      dopamine and non-dopamine VTA neurons and mPFC neurons encode the relationship
      between action and punishment. At the network level, we found that coherent theta
      oscillations synchronize VTA and mPFC in a bottom-up direction, effectively phase
      modulating the neuronal spike activity in the two regions during punishment-free
      actions. This synchrony declined as a function of punishment probability,
      suggesting that during reward-seeking actions, risk of punishment diminishes VTA
      driven neural synchrony between the two regions.

PMID- 29058674
TI  - Conserved neural circuit structure across Drosophila larval development revealed
      by comparative connectomics.
AB  - During postembryonic development, the nervous system must adapt to a growing
      body. How changes in neuronal structure and connectivity contribute to the
      maintenance of appropriate circuit function remains unclear. Previously , we
      measured the cellular neuroanatomy underlying synaptic connectivity in Drosophila
      (Schneider-Mizell et al., 2016). Here, we examined how neuronal morphology and
      connectivity change between first instar and third instar larval stages using
      serial section electron microscopy. We reconstructed nociceptive circuits in a
      larva of each stage and found consistent topographically arranged connectivity
      between identified neurons. Five-fold increases in each size, number of terminal
      dendritic branches, and total number of synaptic inputs were accompanied by cell
      type-specific connectivity changes that preserved the fraction of total synaptic
      input associated with each pre-synaptic partner. We propose that precise patterns
      of structural growth act to conserve the computational function of a circuit, for
      example determining the location of a dangerous stimulus.

PMID- 29058675
TI  - Dendritic small conductance calcium-activated potassium channels activated by
      action potentials suppress EPSPs and gate spike-timing dependent synaptic
      plasticity.
AB  - Small conductance calcium-activated potassium channels (SK channels) are present
      in spines and can be activated by backpropagating action potentials (APs). This
      suggests they may play a critical role in spike-timing dependent synaptic
      plasticity (STDP). Consistent with this idea, EPSPs in both cortical and
      hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent
      manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended
      on their precise timing as well as the distance of activated synapses from the
      soma, was dendritic in origin, and involved SK-dependent suppression of NMDA
      receptor activation. As a result SK channel activation by backpropagating APs
      gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD
      absent under control conditions but present after SK channel block. These
      findings indicate that activation of SK channels in spines by backpropagating APs
      plays a key role in regulating both EPSP amplitude and STDP induction.

PMID- 29058676
TI  - Model-based local density sharpening of cryo-EM maps.
AB  - Atomic models based on high-resolution density maps are the ultimate result of
      the cryo-EM structure determination process. Here, we introduce a general
      procedure for local sharpening of cryo-EM density maps based on prior knowledge
      of an atomic reference structure. The procedure optimizes contrast of cryo-EM
      densities by amplitude scaling against the radially averaged local falloff
      estimated from a windowed reference model. By testing the procedure using six
      cryo-EM structures of TRPV1, beta-galactosidase, gamma-secretase, ribosome-EF-Tu
      complex, 20S proteasome and RNA polymerase III, we illustrate how local
      sharpening can increase interpretability of density maps in particular in cases
      of resolution variation and facilitates model building and atomic model
      refinement.

PMID- 29058677
TI  - Coupling chemosensory array formation and localization.
AB  - Chemotaxis proteins organize into large, highly ordered, chemotactic signaling
      arrays, which in Vibrio species are found at the cell pole. Proper localization
      of signaling arrays is mediated by ParP, which tethers arrays to a cell pole
      anchor, ParC. Here we show that ParP's C-terminus integrates into the core-unit
      of signaling arrays through interactions with MCP-proteins and CheA. Its
      intercalation within core-units stimulates array formation, whereas its N
      terminal interaction domain enables polar recruitment of arrays and facilitates
      its own polar localization. Linkage of these domains within ParP couples array
      formation and localization and results in controlled array positioning at the
      cell pole. Notably, ParP's integration into arrays modifies its own and ParC's
      subcellular localization dynamics, promoting their polar retention. ParP serves
      as a critical nexus that regulates the localization dynamics of its network
      constituents and drives the localized assembly and stability of the chemotactic
      machinery, resulting in proper cell pole development.

PMID- 29058678
TI  - Computer assisted detection of axonal bouton structural plasticity in in vivo
      time-lapse images.
AB  - The ability to measure minute structural changes in neural circuits is essential
      for long-term in vivo imaging studies. Here, we propose a methodology for
      detection and measurement of structural changes in axonal boutons imaged with
      time-lapse two-photon laser scanning microscopy (2PLSM). Correlative 2PLSM and 3D
      electron microscopy (EM) analysis, performed in mouse barrel cortex, showed that
      the proposed method has low fractions of false positive/negative bouton
      detections (2/0 out of 18), and that 2PLSM-based bouton weights are correlated
      with their volumes measured in EM (r = 0.93). Next, the method was applied to a
      set of axons imaged in quick succession to characterize measurement uncertainty.
      The results were used to construct a statistical model in which bouton addition,
      elimination, and size changes are described probabilistically, rather than being
      treated as deterministic events. Finally, we demonstrate that the model can be
      used to quantify significant structural changes in boutons in long-term imaging
      experiments.

PMID- 29058680
TI  - Two-dimensional thio- and seleno-cyanates of Mo and W.
AB  - The stability of two-dimensional (2D) transition metal di-chalcogenides (TMDC) is
      controlled by the fact that sulfur or selenium atoms can cap the 2D layers
      without exposing highly reactive bonds. Here we use first-principles calculations
      to show that a similar structural motif can stabilize Mo- and W-based 2D
      materials with thio- or seleno-cyanate groups. In particular, we show that the
      formation of Mo(SeCN)2, W(SCN)2 and W(SeCN)2 sheets is energetically favorable
      and can lead to various configurations that resemble the well-known polymorphs of
      TMDCs. The lowest-energy structures are small-gap semiconductors, while certain
      polytypes bear Dirac-like cones close to the Fermi energy, demonstrating the
      potential of these new 2D materials for applications in modern electronic
      devices.

PMID- 29058681
TI  - Optimization of binding B-lymphocytes in a microfluidic channel: surface
      modification, stasis time and shear response.
AB  - Binding and maintaining cells inside microfluidic channels is a challenging task
      due to the potential release of cells from the channels with the flow and
      accompanying shear stress. In this work we optimized the binding of human B
      lymphocyte cells (HR1K) inside a microfluidic channel and determined the strength
      of this binding under shear stress of flowing liquid. In order to determine the
      parameters required for a live/dead test in microfluidic devices, populations of
      both living and dead cells were tested separately. Channels were prepared in
      glass-polydimethylsiloxane hybrid chips, with a self-assembled monolayer of 3
      (glycidyloxypropyl)trimethoxysilane (GPTMS) before covalently immobilizing anti
      CD20 antibody. Without GPTMS linker, ~90% of the CD20-expressing cells detached
      at 200 MUl min-1 (the highest flow rate studied). With GPTMS linker, the bonding
      method proved critical for sustained immobilization of HR1K cells under flow.
      Masking the channel area during plasma bonding preserves the antibody
      functionality; the masked surface gives 15% cell detachment at 200 MUl min-1
      compared with 80% for an unmasked surface. Sealing the chip via clamping (without
      plasma treatment) was similar to masked plasma treatment (20% detachment) and
      allowing a post-adhesion stasis time (30 min) did not significantly change the
      relative cell detachment for the flow rates studied. Membrane integrity and
      calcium spiking behaviour were measured fluorescently, and demonstrated that the
      live cells retained comparable functionality to unanchored cells for the duration
      of the flow experiments. Non-viable HR1K cells were found to detach more readily,
      exhibiting only 20% cell retention at 200 MUl min-1 compared with >80% for live
      cells.

PMID- 29058679
TI  - Inter-dependent apical microtubule and actin dynamics orchestrate centrosome
      retention and neuronal delamination.
AB  - Detachment of newborn neurons from the neuroepithelium is required for correct
      neuronal architecture and functional circuitry. This process, also known as
      delamination, involves adherens-junction disassembly and acto-myosin-mediated
      abscission, during which the centrosome is retained while apical/ciliary
      membranes are shed. Cell-biological mechanisms mediating delamination are,
      however, poorly understood. Using live-tissue and super-resolution imaging, we
      uncover a centrosome-nucleated wheel-like microtubule configuration, aligned with
      the apical actin cable and adherens-junctions within chick and mouse
      neuroepithelial cells. These microtubules maintain adherens-junctions while actin
      maintains microtubules, adherens-junctions and apical end-foot dimensions. During
      neuronal delamination, acto-myosin constriction generates a tunnel-like actin
      microtubule configuration through which the centrosome translocates. This
      movement requires inter-dependent actin and microtubule activity, and we identify
      drebrin as a potential coordinator of these cytoskeletal dynamics. Furthermore,
      centrosome compromise revealed that this organelle is required for delamination.
      These findings identify new cytoskeletal configurations and regulatory
      relationships that orchestrate neuronal delamination and may inform mechanisms
      underlying pathological epithelial cell detachment.

PMID- 29058682
TI  - Small composite field correction factors for the CyberKnife radiosurgery system:
      clinical and PCSR plans.
AB  - A formalism has been proposed for small and non-standard photon fields in which
      [Formula: see text] correction factors are used to correct dosimeter response in
      small fields (indiviual or composite) relative to that in a larger machine
      specific reference (MSR) field. For clinical plans consisting of several fields,
      a plan-class specific reference (PCSR) plan can also be defined, serving as an
      intermediate calibration field between the MSR and clinical plans within a
      certain plan-class. In this work, the formalism was applied in the calculation of
      [Formula: see text] for 21 clinical plans delivered by the [Formula: see text]
      radiosurgery system, each plan employing one or two of the smallest diameter
      collimators: 5 mm, 7.5 mm, and 10 mm. Three detectors were considered: the
      Exradin A16 and A26 micro chambers, and the W1 plastic scintillator. The clinical
      plans were grouped into 7 plan-classes according to commonly shared
      characteristics. The suitability of using a PCSR plan to represent the detector
      response of each plan within the plan-class was investigated. Total and
      intermediate correction factors were calculated using the [Formula: see text]
      Monte Carlo user code. The corrections for the micro chambers were large,
      primarily due to the presence of the low-density air cavity and the volume
      averaging effect. The correction for the scintillator was found to be close to
      unity for most plans, indicating that this detector may be used to measure small
      clinical plan correction factors in any plan except for those using the 5 mm
      collimator. The PCSR plan was shown to be applicable to plan-classes comprising
      isocentric plans only, with plan-classes divided according to collimator size.
      For non-isocentric plans, the variation of [Formula: see text] as a function of
      the point of measurement within a single plan, as well as the high inter-plan
      class variability of the correction factor, precludes the use of a PCSR plan.

PMID- 29058683
TI  - Cooperative mechanosensitivity and allostery of focal adhesion clusters.
AB  - We analyse the role of cooperative interaction between neighbouring adhesion
      mechanosensor complexes by constructing an Ising-like Hamiltonian describing the
      free energy of cell adhesion on a substrate as a lattice of 3-state
      mechanosensing sites involving focal adhesion kinase (FAK). We use a Monte Carlo
      stochastic algorithm to find equilibrium configurations of these mechanosensors
      in two representative geometries: on a 1D ring representing the rim of a cell on
      a flat surface, and a 2D bounded surface representing the whole area of cell
      contact with a flat surface. The level of FAK activation depends on the pulling
      force applied to the individual FAK-integrin via actin-myosin contractile
      networks, and the details of the coupling between individual sensors in a
      cluster. Strong coupling is shown to make the FAK sensors experience a sharp on
      off behaviour in their activation, while at low coupling the
      activation/autoinhibition transition occurs over a broad range of pulling force.
      We find that the activation/autoinhibition transition of FAK in the 2D system
      with strong coupling occurs with a hysteresis, the width of which depends on the
      rate of change of force. The effect of introducing a regulating protein (such as
      Src) in a limited quantity to control FAK activation is explored, and
      visualizations of clustering in both topologies are presented. In particular the
      results on the bounded 2D surface indicate that clustering of active FAK occurs
      preferentially at the boundary, in agreement with experimental observations of
      focal adhesions in cells.

PMID- 29058684
TI  - Electrospun polycaprolactone nanofibres decorated by drug loaded chitosan nano
      reservoirs for antibacterial treatments.
AB  - The main limitation of conventional antibiotic therapies concerns the low
      efficacy to fight bacteria attacks during long treatment times. In this context,
      the integrated use of electrofluidodynamics (EFDs)-basically electrospinning and
      electrospraying-may represent an interesting route for designing nanostructured
      platforms with controlled release to prevent the formation of bacterial biofilms
      in oral implant sites. They allow for the deposition of nanofibres and
      nanoparticles by different modes-i.e. sequential, simultaneous-for the
      fabrication of more efficacious systems in terms of degradation protection,
      pharmacokinetic control and drug distribution to the surrounding tissues. Herein,
      we will investigate EFDs processing modes and conditions to decorate
      polycaprolactone nanofibres surfaces by chitosan nano-reservoirs for the
      administration of Amoxicillin Trihydrate as an innovative antibacterial treatment
      of the periodontal pocket.

PMID- 29058685
TI  - Study for online range monitoring with the interaction vertex imaging method.
AB  - Ion beam therapy enables a highly accurate dose conformation delivery to the
      tumor due to the finite range of charged ions in matter (i.e. Bragg peak (BP)).
      Consequently, the dose profile is very sensitive to patients anatomical changes
      as well as minor mispositioning, and so it requires improved dose control
      techniques. Proton interaction vertex imaging (IVI) could offer an online range
      control in carbon ion therapy. In this paper, a statistical method was used to
      study the sensitivity of the IVI technique on experimental data obtained from the
      Heidelberg Ion-Beam Therapy Center. The vertices of secondary protons were
      reconstructed with pixelized silicon detectors. The statistical study used the
      [Formula: see text] test of the reconstructed vertex distributions for a given
      displacement of the BP position as a function of the impinging carbon ions.
      Different phantom configurations were used with or without bone equivalent tissue
      and air inserts. The inflection points in the fall-off region of the longitudinal
      vertex distribution were computed using different methods, while the relation
      with the BP position was established. In the present setup, the resolution of the
      BP position was about 4-5 mm in the homogeneous phantom under clinical conditions
      (106 incident carbon ions). Our results show that the IVI method could therefore
      monitor the BP position with a promising resolution in clinical conditions.

PMID- 29058686
TI  - Single-source PPG-based local pulse wave velocity measurement: a potential
      cuffless blood pressure estimation technique.
AB  - OBJECTIVE: A novel photoplethysmograph probe employing dual photodiodes excited
      using a single infrared light source was developed for local pulse wave velocity
      (PWV) measurement. The potential use of the proposed system in cuffless blood
      pressure (BP) techniques was demonstrated. APPROACH: Initial validation
      measurements were performed on a phantom using a reference method. Further, an in
      vivo study was carried out in 35 volunteers (age  =  28  +/-  4.5 years). The
      carotid local PWV, carotid to finger pulse transit time (PTTR) and pulse arrival
      time at the carotid artery (PATC) were simultaneously measured. Beat-by-beat
      variation of the local PWV due to BP changes was studied during post-exercise
      relaxation. The cuffless BP estimation accuracy of local PWV, PATC, and PTTR was
      investigated based on inter- and intra-subject models with best-case calibration.
      MAIN RESULTS: The accuracy of the proposed system, hardware inter-channel delay
      (<0.1 ms), repeatability (beat-to-beat variation  =  4.15%-11.38%) and
      reproducibility of measurement (r  =  0.96) were examined. For the phantom
      experiment, the measured PWV values did not differ by more than 0.74 m s-1
      compared to the reference PWV. Better correlation was observed between brachial
      BP parameters versus local PWV (r  =  0.74-0.78) compared to PTTR (|r|  =  0.62
      0.67) and PATC (|r|  =  0.52-0.68). Cuffless BP estimation using local PWV was
      better than PTTR and PATC with population-specific models. More accurate
      estimates of arterial BP levels were achieved using local PWV via subject
      specific models (root-mean-square error  ?2.61 mmHg). SIGNIFICANCE: A reliable
      system for cuffless BP measurement and local estimation of arterial wall
      properties.

PMID- 29058687
TI  - Planning, guidance, and quality assurance of pelvic screw placement using
      deformable image registration.
AB  - Percutaneous pelvic screw placement is challenging due to narrow bone corridors
      surrounded by vulnerable structures and difficult visual interpretation of
      complex anatomical shapes in 2D x-ray projection images. To address these
      challenges, a system for planning, guidance, and quality assurance (QA) is
      presented, providing functionality analogous to surgical navigation, but based on
      robust 3D-2D image registration techniques using fluoroscopy images already
      acquired in routine workflow. Two novel aspects of the system are investigated:
      automatic planning of pelvic screw trajectories and the ability to account for
      deformation of surgical devices (K-wire deflection). Atlas-based registration is
      used to calculate a patient-specific plan of screw trajectories in preoperative
      CT. 3D-2D registration aligns the patient to CT within the projective geometry of
      intraoperative fluoroscopy. Deformable known-component registration (dKC-Reg)
      localizes the surgical device, and the combination of plan and device location is
      used to provide guidance and QA. A leave-one-out analysis evaluated the accuracy
      of automatic planning, and a cadaver experiment compared the accuracy of dKC-Reg
      to rigid approaches (e.g. optical tracking). Surgical plans conformed within the
      bone cortex by 3-4 mm for the narrowest corridor (superior pubic ramus) and  >5
      mm for the widest corridor (tear drop). The dKC-Reg algorithm localized the K
      wire tip within 1.1 mm and 1.4 degrees  and was consistently more accurate than
      rigid-body tracking (errors up to 9 mm). The system was shown to automatically
      compute reliable screw trajectories and accurately localize deformed surgical
      devices (K-wires). Such capability could improve guidance and QA in orthopaedic
      surgery, where workflow is impeded by manual planning, conventional tool trackers
      add complexity and cost, rigid tool assumptions are often inaccurate, and
      qualitative interpretation of complex anatomy from 2D projections is prone to
      trial-and-error with extended fluoroscopy time.

PMID- 29058688
TI  - Small GTPase ARF6 controls VEGFR2 trafficking and signaling in diabetic
      retinopathy.
AB  - The devastating sequelae of diabetes mellitus include microvascular permeability,
      which results in retinopathy. Despite clinical and scientific advances, there
      remains a need for new approaches to treat retinopathy. Here, we have presented a
      possible treatment strategy, whereby targeting the small GTPase ARF6 alters
      VEGFR2 trafficking and reverses signs of pathology in 4 animal models that
      represent features of diabetic retinopathy and in a fifth model of ocular
      pathological angiogenesis. Specifically, we determined that the same signaling
      pathway utilizes distinct GEFs to sequentially activate ARF6, and these GEFs
      exert distinct but complementary effects on VEGFR2 trafficking and signal
      transduction. ARF6 activation was independently regulated by 2 different ARF GEFs
      - ARNO and GEP100. Interaction between VEGFR2 and ARNO activated ARF6 and
      stimulated VEGFR2 internalization, whereas a VEGFR2 interaction with GEP100
      activated ARF6 to promote VEGFR2 recycling via coreceptor binding. Intervening in
      either pathway inhibited VEGFR2 signal output. Finally, using a combination of in
      vitro, cellular, genetic, and pharmacologic techniques, we demonstrated that ARF6
      is pivotal in VEGFR2 trafficking and that targeting ARF6-mediated VEGFR2
      trafficking has potential as a therapeutic approach for retinal vascular diseases
      such as diabetic retinopathy.

PMID- 29058689
TI  - Deficiency of tumor suppressor NDRG2 leads to attention deficit and hyperactive
      behavior.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric
      disorder in children. Although an imbalance of excitatory and inhibitory inputs
      has been proposed as contributing to this disorder, the mechanisms underlying
      this highly heterogeneous disease remain largely unknown. Here, we show that N
      myc downstream-regulated gene 2 (NDRG2) deficiency is involved in the development
      of ADHD in both mice and humans. Ndrg2-knockout (Ndrg2-/-) mice exhibited ADHD
      like symptoms characterized by attention deficits, hyperactivity, impulsivity,
      and impaired memory. Furthermore, interstitial glutamate levels and excitatory
      transmission were markedly increased in the brains of Ndrg2-/- mice due to
      reduced astroglial glutamate clearance. We developed an NDRG2 peptide that
      rescued astroglial glutamate clearance and reduced excitatory glutamate
      transmission in NDRG2-deficient astrocytes. Additionally, NDRG2 peptide treatment
      rescued ADHD-like hyperactivity in the Ndrg2-/- mice, while routine
      methylphenidate treatment had no effect on hyperactivity in these animals.
      Finally, children who were heterozygous for rs1998848, a SNP in NDRG2, had a
      higher risk of ADHD than children who were homozygous for rs1998848. Our results
      indicate that NDRG2 deficiency leads to ADHD phenotypes and that impaired
      astroglial glutamate clearance, a mechanism distinct from the well-established
      dopamine deficit hypothesis for ADHD, underlies the resultant behavioral
      abnormalities.

PMID- 29058690
TI  - Advillin acts upstream of phospholipase C epsilon1 in steroid-resistant nephrotic
      syndrome.
AB  - Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney
      disease. Here, we identified recessive mutations in the gene encoding the actin
      binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL
      mutations resulted in a marked loss of its actin-bundling ability, truncation of
      AVIL also disrupted colocalization with F-actin, thereby leading to impaired
      actin binding and severing. Additionally, AVIL colocalized and interacted with
      the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex.
      Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell
      periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked
      EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the
      podocyte migration rate (PMR). These effects were reversed by overexpression of
      WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants.
      The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF
      stimulation; however, this increased PMR was ameliorated by inhibition of the
      ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs
      downstream of AVIL and PLCE1 function. Together, these results delineate a
      comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with
      alterations in the action of PLCE1, an established SRNS protein.

PMID- 29058692
TI  - Microscopy of Common Nail Cosmetics.
AB  - Nail clipping specimens are commonly submitted for the microscopic evaluation of
      nail disease; however, there may be missing clinical history regarding nail
      polish or other adornments present on the nail at the time of specimen retrieval.
      For this study, 6 types of nail cosmetics were chosen and applied to the nail
      plate of a volunteer. After a period of at least 24 hours, the nail plates with
      adornments and a control nail plate were clipped and placed in formalin.
      Specimens were processed using a standard nail protocol. All of the specimens,
      except the sticker applique, survived the fixation process. The glitter nail
      polish was the only specimen found to be polarizable. None of the specimens that
      survived fixation were found to be PAS-positive. Cosmetic nail enhancements are
      easily differentiated from the nail plate microscopically; nail cosmetics appear
      as a distinct layer of inorganic material lying atop the nail plate. There were 2
      main microscopic patterns noted on the specimens: those with 2 layers and those
      with 3 layers.

PMID- 29058691
TI  - Endothelial jagged-2 sustains hematopoietic stem and progenitor reconstitution
      after myelosuppression.
AB  - Angiocrine factors, such as Notch ligands, supplied by the specialized
      endothelial cells (ECs) within the bone marrow and splenic vascular niche play an
      essential role in modulating the physiology of adult hematopoietic stem and
      progenitor cells (HSPCs). However, the relative contribution of various Notch
      ligands, specifically jagged-2, to the homeostasis of HSPCs is unknown. Here, we
      show that under steady state, jagged-2 is differentially expressed in tissue
      specific vascular beds, but its expression is induced in hematopoietic vascular
      niches after myelosuppressive injury. We used mice with EC-specific deletion of
      the gene encoding jagged-2 (Jag2) to demonstrate that while EC-derived jagged-2
      was dispensable for maintaining the capacity of HSPCs to repopulate under steady
      state conditions, by activating Notch2 it did contribute to the recovery of HSPCs
      in response to myelosuppressive conditions. Engraftment and/or expansion of HSPCs
      was dependent on the expression of endothelial-derived jagged-2 following
      myeloablation. Additionally, jagged-2 expressed in bone marrow ECs regulated HSPC
      cell cycle and quiescence during regeneration. Endothelial-deployed jagged-2
      triggered Notch2/Hey1, while tempering Notch2/Hes1 signaling in HSPCs.
      Collectively, these data demonstrate that EC-derived jagged-2 activates Notch2
      signaling in HSPCs to promote hematopoietic recovery and has potential as a
      therapeutic target to accelerate balanced hematopoietic reconstitution after
      myelosuppression.

PMID- 29058693
TI  - Pathological Sampling of Basal Cell Carcinoma Re-excision Specimens: How Much is
      Enough?
AB  - Basal cell carcinoma (BCC) is the most common cutaneous malignancy, comprising
      approximately 75%-80% of all skin cancers. Surgical excision is the most common
      first line treatment modality, with the intent of obtaining clear margins. If the
      initial excision is incomplete or inadequate, a re-excision will often be
      performed in an attempt to achieve histological clearance. The pathological
      examination of these specimens requires a balance between the need for adequate
      assessment and efficient use of laboratory resources. In this study, we sought to
      systematically compare different approaches to the pathological sampling of these
      specimens in the hope of providing an evidential basis for a rational approach.
      Seventy-four BCC re-excision specimens were entirely sampled and retrospectively
      examined to determine the rate of detection of residual BCC which would have been
      achieved using different sampling methodologies. Residual BCC was identified in
      37 specimens (50%). Limited transverse sections through the centre of the ellipse
      resulted in a sensitivity for detection of residual BCC of 78% (or 85% if only
      "significant" residual tumor is considered). By including the entire scar or the
      remainder of the specimen except the polar pieces, the sensitivity improved to
      95% and 97%, respectively. Only one case showed residual tumor in the apical
      sections alone, with tumor extending to the new surgical margin in that case. We
      hope that this data may help laboratories develop sampling protocols appropriate
      to their own cost-benefit analyses and patient populations.

PMID- 29058694
TI  - Nail Matrix Pathology in Cronkhite-Canada Syndrome: The First Case Report.
AB  - Cronkhite-Canada Syndrome (CCS) presents with gastrointestinal polyposis and the
      triad of cutaneous abnormalities including nail dystrophy, alopecia, and
      hyperpigmentation of the skin. The etiology is not well understood. The histology
      of skin lesion in CCS has not been routinely described. Especially, the nail
      matrix pathology has not been reported. In this study, the authors report the
      nail matrix pathology in a patient with CCS. Interestingly, the histologic
      evaluation revealed matrix hypergranulosis. Because matrix hypergranulosis is
      commonly found in several inflammatory nail diseases, this discovery points out
      that an inflammatory process is probably one of the important pathogeneses in
      CCS.

PMID- 29058696
TI  - Donor and recipient plasma follistatin levels are associated with acute GvHD in
      Blood and Marrow Transplant Clinical Trials Network 0402.
AB  - Follistatin is an angiogenic factor elevated in the circulation after allogeneic
      hematopoietic cell transplantation (HCT). Elevations in follistatin plasma
      concentrations are associated with the onset of and poor survival after acute
      GvHD (aGvHD). Using data from the Blood and Marrow Transplant Clinical Trials
      Network 0402 study (n=247), we sought to further quantify the longitudinal
      associations between plasma follistatin levels in transplant recipients, as well
      as baseline HCT donor follistatin levels, and allogeneic HCT outcomes. Higher
      recipient baseline follistatin levels were predictive of development of aGvHD
      (P=0.04). High donor follistatin levels were also associated with the incidence
      of aGvHD (P<0.01). Elevated follistatin levels on day 28 were associated with the
      onset of grade II-IV aGvHD before day 28, higher 1-year non-relapse mortality
      (NRM) and lower overall survival. In multivariate analyses, individuals with
      follistatin levels >1088 pg/mL at day 28 had a 4-fold increased risk for NRM
      (relative risk (RR)=4.3, 95% confidence interval (CI) 1.9-9.9, P<0.01) and a
      nearly three-fold increased overall risk for mortality (RR=2.8, 95% CI 1.5-5.2,
      P<0.01). Given the multiple roles of follistatin in tissue inflammation and
      repair, and the confirmation that this biomarker is predictive of important HCT
      outcomes, the pathobiology of these relationships need further study.

PMID- 29058695
TI  - DNA methylation signal has a major role in the response of human breast cancer
      cells to the microenvironment.
AB  - Breast cancer-associated fibroblasts (CAFs) have a crucial role in tumor
      initiation, metastasis and therapeutic resistance by secreting various growth
      factors, cytokines, protease and extracellular matrix components. Soluble factors
      secreted by CAFs are involved in many pathways including inflammation,
      metabolism, proliferation and epigenetic modulation, suggesting that CAF
      dependent reprograming of cancer cells affects a large set of genes. This
      paracrine signaling has an important role in tumor progression, thus deciphering
      some of these processes could lead to relevant discoveries with subsequent
      clinical implications. Here, we investigated the mechanisms underlying the
      changes in gene expression patterns associated with the cross-talk between breast
      cancer cells and the stroma. From RNAseq data obtained from breast cancer cell
      lines grown in presence of CAF-secreted factors, we identified 372 upregulated
      genes, exhibiting an expression level positively correlated with the stromal
      content of breast cancer specimens. Furthermore, we observed that gene expression
      changes were not mediated through significant DNA methylation changes.
      Nevertheless, CAF-secreted factors but also stromal content of the tumors
      remarkably activated specific genes characterized by a DNA methylation pattern:
      hypermethylation at transcription start site and shore regions. Experimental
      approaches (inhibition of DNA methylation, knockdown of methyl-CpG-binding domain
      protein 2 and chromatin immunoprecipitation assays) indicated that this set of
      genes was epigenetically controlled. These data elucidate the importance of
      epigenetics marks in the cancer cell reprogramming induced by stromal cell and
      indicated that the interpreters of the DNA methylation signal have a major role
      in the response of the cancer cells to the microenvironment.

PMID- 29058697
TI  - Viral-specific T-cell transfer from HSCT donor for the treatment of viral
      infections or diseases after HSCT.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option
      for treatment of some malignant and non-malignant hematological diseases.
      However, post-HSCT patients are severely immunocompromised and susceptible to
      viral infections, which are a major cause of morbidity and mortality. Although
      antiviral agents are now available for most types of viral infections, they are
      not devoid of side effects and their efficacy is limited when there is no
      concomitant antiviral immune reconstitution. In recent decades, adoptive transfer
      of viral-specific T cells (VSTs) became an alternative treatment for viral
      infection after HSCT. However, two major issues are concerned in VST transfer:
      the risk of GVHD and antiviral efficacy. We report an exhaustive review of the
      published studies that focus on prophylactic and/or curative therapy by donor VST
      transfer for post-HSCT common viral infections. A low incidence of GVHD and a
      good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT
      donor. Viral-specific T-cell transfer is a promising approach for a broad
      clinical application. Nevertheless, a randomized controlled study in a large
      cohort of patients comparing antiviral treatment alone to antiviral treatment
      combined with VSTs is still needed to demonstrate efficacy and safety.

PMID- 29058698
TI  - Foiling fungal disease post hematopoietic cell transplant: review of prophylactic
      strategies.
AB  - Hematopoietic cell transplantation (HCT) offers definitive management for a wide
      variety of malignant and nonmalignant diseases. Conditioning regimens and
      therapies used to prevent and treat GvHD are immune suppressive, often increasing
      the risk of developing fungal disease due to yeasts or molds. Antifungal
      prophylaxis may be useful in preventing morbidity and mortality during and after
      HCT. In this article, we review the epidemiology and current literature regarding
      strategies for prevention of invasive fungal disease (IFD) in the pre-engraftment
      and post-engraftment settings, and propose future direction for scientific
      discovery.

PMID- 29058699
TI  - Transbronchial biopsy in the management of pulmonary complications of
      hematopoietic stem cell transplantation.
AB  - The utility of transbronchial biopsy in the management of pulmonary complications
      following hematopoietic stem cell transplantation (HSCT) has shown variable
      results. Herein, we examine the largest case series of patients undergoing
      transbronchial biopsy following HSCT. We performed a retrospective analysis of
      130 transbronchial biopsy cases performed in patients with pulmonary
      complications post HSCT. Logistic regression models were applied to examine
      diagnostic yield, odds of therapy change and complications. The most common
      histologic finding on transbronchial biopsy was a nonspecific interstitial
      pneumonitis (n=24 cases, 18%). Pathogens identified by transbronchial biopsy were
      rare, occurring in <5% of cases. A positive transbronchial biopsy significantly
      increased the odds of a subsequent change in corticosteroid therapy (odds ratio
      (OR)=3.12; 95% confidence interval (CI) 1.18-8.23; P=0.02) but was not associated
      with a change in antibiotic therapy (OR=1.01; 95% CI 0.40-2.54; P=0.98) or
      changes in overall therapy (OR=1.92; 95% CI 0.79-4.70; P=0.15). Patients who
      underwent a transbronchial biopsy had increased odds of complications related to
      the bronchoscopy (OR=3.33, 95% CI 1.63-6.79; P=0.001). In conclusion,
      transbronchial biopsy may contribute to the diagnostic management of
      noninfectious lung injury post HSCT, whereas its utility in the management of
      infectious pulmonary complications of HSCT remains low.

PMID- 29058700
TI  - Correlation between pediatric donor characteristics and cell compositions in
      mixture allografts of combined G-CSF-mobilized PBSCs and bone marrow allografts.

PMID- 29058701
TI  - NSAID treatment with meloxicam enhances peripheral stem cell mobilization in
      myeloma.
AB  - Chemotherapy with G-CSF is used to mobilize peripheral stem cells in multiple
      myeloma (MM) patients, with plerixafor as a rescue strategy for poorly mobilizing
      patients. Preclinical studies suggested that the nonsteroidal anti-inflammatory
      drug meloxicam enhances the mobilization of CD34+ cells. In this single-center
      study, we evaluated whether adding meloxicam to chemotherapy/G-CSF mobilization
      increases peripheral hematopoietic CD34+ cell levels and reduces the need of
      using plerixafor. We prospectively compared two consecutive cohorts of MM
      patients in first remission mobilized with G-CSF and non-myelosuppressive
      chemotherapy with vinorelbine or gemcitabine. The second cohort additionally
      received oral meloxicam. The cohorts comprised 84 patients without meloxicam (-M)
      and 66 patients with meloxicam (+M). Meloxicam was well tolerated and associated
      with similar hematologic engraftment after transplantation and equal survival
      rates. However, the meloxicam group had higher CD34+ cell levels on day 8 of the
      mobilization procedure (53 200 versus 35 600 CD34+ cells/mL; P=0.007), and fewer
      patients needed >1 collection day (+M: 6 (9%) patients versus -M: 16 (19%)
      patients; P=0.04). This resulted in reduced plerixafor administrations (+M: 7
      (11%) patients versus -M: 18 (21%) patients; P=0.03) and less costs. Our data
      suggest that meloxicam enhances the mobilization of hematopoietic CD34+ blood
      cells in MM patients.

PMID- 29058702
TI  - Direction of leukocyte polarization and migration by the phosphoinositide
      transfer protein TIPE2.
AB  - The polarization of leukocytes toward chemoattractants is essential for the
      directed migration (chemotaxis) of leukocytes. How leukocytes acquire polarity
      after encountering chemical gradients is not well understood. We found here that
      leukocyte polarity was generated by TIPE2 (TNFAIP8L2), a transfer protein for
      phosphoinositide second messengers. TIPE2 functioned as a local enhancer of
      phosphoinositide-dependent signaling and cytoskeleton remodeling, which promoted
      leading-edge formation. Conversely, TIPE2 acted as an inhibitor of the GTPase
      Rac, which promoted trailing-edge polarization. Consequently, TIPE2-deficient
      leukocytes were defective in polarization and chemotaxis, and TIPE2-deficient
      mice were resistant to leukocyte-mediated neural inflammation. Thus, the
      leukocyte polarizer is a dual-role phosphoinositide-transfer protein and
      represents a potential therapeutic target for the treatment of inflammatory
      diseases.

PMID- 29058703
TI  - Metabolic shift induced by systemic activation of T cells in PD-1-deficient mice
      perturbs brain monoamines and emotional behavior.
AB  - T cells reorganize their metabolic profiles after being activated, but the
      systemic metabolic effect of sustained activation of the immune system has
      remained unexplored. Here we report that augmented T cell responses in Pdcd1-/-
      mice, which lack the inhibitory receptor PD-1, induced a metabolic serum
      signature characterized by depletion of amino acids. We found that the depletion
      of amino acids in serum was due to the accumulation of amino acids in activated
      Pdcd1-/- T cells in the lymph nodes. A systemic decrease in tryptophan and
      tyrosine led to substantial deficiency in the neurotransmitters serotonin and
      dopamine in the brain, which resulted in behavioral changes dominated by anxiety
      like behavior and exacerbated fear responses. Together these data indicate that
      excessive activation of T cells causes a systemic metabolomic shift with
      consequences that extend beyond the immune system.

PMID- 29058704
TI  - Nuclear functions of NME proteins.
AB  - The NME family of proteins is composed of 10 isoforms, designated NME1-10, which
      are diverse in their enzymatic activities and patterns of subcellular
      localization. Each contains a conserved domain associated with a nucleoside
      diphosphate kinase (NDPK) function, although not all are catalytically active.
      Several of the NME isoforms (NME1, NME5, NME7, and NME8) also exhibit a 3'-5'
      exonuclease activity, suggesting roles in DNA proofreading and repair. NME1 and
      NME2 have been shown to translocate to the nucleus, although they lack a
      canonical nuclear localization signal. Binding of NME1 and NME2 to DNA does not
      appear to be sequence-specific in a strict sense, but instead is directed to
      single-stranded regions and/or other non-B-form structures. NME1 and NME2 have
      been identified as potential canonical transcription factors that regulate gene
      transcription through their DNA-binding activities. Indeed, the NME1 and NME2
      isoforms have been shown to regulate gene expression programs in a number of
      cellular settings, and this regulatory function has been proposed to underlie
      their well-recognized ability to suppress the metastatic phenotype of cancer
      cells. Moreover, NME1 and, more recently, NME3, have been implicated in repair of
      both single- and double-stranded breaks in DNA. This suggests that reduced
      expression of NME proteins could contribute to the genomic instability that
      drives cancer progression. Clearly, a better understanding of the nuclear
      functions of NME1 and possibly other NME isoforms could provide critical insights
      into mechanisms underlying malignant progression in cancer. Indeed, clinical data
      indicate that the subcellular localization of NME1 may be an important prognostic
      marker in some cancers. This review summarizes putative functions of nuclear NME
      proteins in DNA binding, transcription, and DNA damage repair, and highlights
      their possible roles in cancer progression.

PMID- 29058705
TI  - Identification of a gene expression signature associated with the metastasis
      suppressor function of NME1: prognostic value in human melanoma.
AB  - Although NME1 is well known for its ability to suppress metastasis of melanoma,
      the molecular mechanisms underlying this activity are not completely understood.
      Herein, we utilized a bioinformatics approach to systematically identify genes
      whose expression is correlated with the metastasis suppressor function of NME1.
      This was accomplished through a search for genes that were regulated by NME1, but
      not by NME1 variants lacking metastasis suppressor activity. This approach
      identified a number of novel genes, such as ALDOC, CXCL11, LRP1b, and XAGE1 as
      well as known targets such as NETO2, which were collectively designated as an
      NME1-Regulated Metastasis Suppressor Signature (MSS). The MSS was associated with
      prolonged overall survival in a large cohort of melanoma patients in The Cancer
      Genome Atlas (TCGA). The median overall survival of melanoma patients with
      elevated expression of the MSS genes was >5.6 years longer compared with that of
      patients with lower expression of the MSS genes. These data demonstrate that NMEl
      represents a powerful tool for identifying genes whose expression is associated
      with metastasis and survival of melanoma patients, suggesting their potential
      applications as prognostic markers and therapeutic targets in advanced forms of
      this lethal cancer.

PMID- 29058708
TI  - Histone propionylation is a mark of active chromatin.
AB  - Histones are highly covalently modified, but the functions of many of these
      modifications remain unknown. In particular, it is unclear how histone marks are
      coupled to cellular metabolism and how this coupling affects chromatin
      architecture. We identified histone H3 Lys14 (H3K14) as a site of propionylation
      and butyrylation in vivo and carried out the first systematic characterization of
      histone propionylation. We found that H3K14pr and H3K14bu are deposited by
      histone acetyltransferases, are preferentially enriched at promoters of active
      genes and are recognized by acylation-state-specific reader proteins. In
      agreement with these findings, propionyl-CoA was able to stimulate transcription
      in an in vitro transcription system. Notably, genome-wide H3 acylation profiles
      were redefined following changes to the metabolic state, and deletion of the
      metabolic enzyme propionyl-CoA carboxylase altered global histone propionylation
      levels. We propose that histone propionylation, acetylation and butyrylation may
      act in combination to promote high transcriptional output and to couple cellular
      metabolism with chromatin structure and function.

PMID- 29058706
TI  - Histidine kinases and the missing phosphoproteome from prokaryotes to eukaryotes.
AB  - Protein phosphorylation is the most common type of post-translational
      modification in eukaryotes. The phosphoproteome is defined as the complete set of
      experimentally detectable phosphorylation sites present in a cell's proteome
      under various conditions. However, we are still far from identifying all the
      phosphorylation sites in a cell mainly due to the lack of information about
      phosphorylation events involving residues other than Ser, Thr and Tyr. Four types
      of phosphate-protein linkage exist and these generate nine different
      phosphoresidues-pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu and pCys. Most of
      the effort in studying protein phosphorylation has been focused on Ser, Thr and
      Tyr phosphorylation. The recent development of 1- and 3-pHis monoclonal
      antibodies promises to increase our understanding of His phosphorylation and the
      kinases and phosphatases involved. Several His kinases are well defined in
      prokaryotes, especially those involved in two-component system (TCS) signaling.
      However, in higher eukaryotes, NM23, a protein originally characterized as a
      nucleoside diphosphate kinase, is the only characterized protein-histidine
      kinase. This ubiquitous and conserved His kinase autophosphorylates its active
      site His, and transfers this phosphate either onto a nucleoside diphosphate or
      onto a protein His residue. Studies of NM23 protein targets using newly developed
      anti-pHis antibodies will surely help illuminate the elusive His phosphorylation
      based signaling pathways. This review discusses the role that the NM23/NME/NDPK
      phosphotransferase has, how the addition of the pHis phosphoproteome will expand
      the phosphoproteome and make His phosphorylation part of the global
      phosphorylation world. It also summarizes why our understanding of
      phosphorylation is still largely restricted to the acid stable phosphoproteome,
      and highlights the study of NM23 histidine kinase as an entree into the world of
      histidine phosphorylation.

PMID- 29058707
TI  - Balance of cardiac and systemic hepcidin and its role in heart physiology and
      pathology.
AB  - Hepcidin is the main regulator of iron metabolism in tissues. Its serum levels
      are mostly correlated with the levels of hepcidin expression from the liver, but
      local hepcidin can be important for the physiology of other organs as well. There
      is an increasing evidence that this is the case with cardiac hepcidin. This has
      been confirmed by studies with models of ischemic heart disease and other heart
      pathologies. In this review the discussion dissects the role of cardiac hepcidin
      in cellular homeostasis. This review is complemented with examination of the role
      of systemic hepcidin in heart disease and its use as a biochemical marker. The
      relationship between systemic vs local hepcidin in the heart is important because
      it can help us understand how the fine balance between the actions of two
      hepcidins affects heart function. Manipulating the axis systemic/cardiac hepcidin
      could serve as a new therapeutic strategy in heart diseases.

PMID- 29058709
TI  - Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by
      RNA.
AB  - Many studies have revealed pathways of epigenetic gene silencing by Polycomb
      repressive complex 2 (PRC2) in vivo, but understanding the underlying molecular
      mechanisms requires biochemistry. Here we analyze interactions of reconstituted
      human PRC2 with nucleosome complexes. Histone modifications, the H3K27M cancer
      mutation, and inclusion of JARID2 or EZH1 in the PRC2 complex have unexpectedly
      minor effects on PRC2-nucleosome binding. Instead, protein-free linker DNA
      dominates the PRC2-nucleosome interaction. Specificity for CG-rich sequences is
      consistent with PRC2 occupying CG-rich DNA in vivo. PRC2 preferentially binds
      methylated DNA regulated by its AEBP2 subunit, suggesting how DNA and histone
      methylation collaborate to repress chromatin. We find that RNA, known to inhibit
      PRC2 activity, is not a methyltransferase inhibitor per se. Instead, RNA
      sequesters PRC2 from nucleosome substrates, because PRC2 binding requires linker
      DNA, and RNA and DNA binding are mutually exclusive. Together, we provide a model
      for PRC2 recruitment and an explanation for how actively transcribed genomic
      regions bind PRC2 but escape silencing.

PMID- 29058710
TI  - DNA binding by PHF1 prolongs PRC2 residence time on chromatin and thereby
      promotes H3K27 methylation.
AB  - Polycomb repressive complex 2 (PRC2) trimethylates histone H3 at lysine 27 to
      mark genes for repression. We measured the dynamics of PRC2 binding on
      recombinant chromatin and free DNA at the single-molecule level using total
      internal reflection fluorescence (TIRF) microscopy. PRC2 preferentially binds
      free DNA with multisecond residence time and midnanomolar affinity. PHF1, a PRC2
      accessory protein of the Polycomblike family, extends PRC2 residence time on DNA
      and chromatin. Crystallographic and functional studies reveal that Polycomblike
      proteins contain a winged-helix domain that binds DNA in a sequence-nonspecific
      fashion. DNA binding by this winged-helix domain accounts for the prolonged
      residence time of PHF1-PRC2 on chromatin and makes it a more efficient H3K27
      methyltranferase than PRC2 alone. Together, these studies establish that
      interactions with DNA provide the predominant binding affinity of PRC2 for
      chromatin. Moreover, they reveal the molecular basis for how Polycomblike
      proteins stabilize PRC2 on chromatin and stimulate its activity.

PMID- 29058711
TI  - The helicase domain of Poltheta counteracts RPA to promote alt-NHEJ.
AB  - Mammalian polymerase theta (Poltheta) is a multifunctional enzyme that promotes
      error-prone DNA repair by alternative nonhomologous end joining (alt-NHEJ). Here
      we present structure-function analyses that reveal that, in addition to the
      polymerase domain, Poltheta-helicase activity plays a central role during double
      strand break (DSB) repair. Our results show that the helicase domain promotes
      chromosomal translocations by alt-NHEJ in mouse embryonic stem cells and also
      suppresses CRISPR-Cas9- mediated gene targeting by homologous recombination (HR).
      In vitro assays demonstrate that Poltheta-helicase activity facilitates the
      removal of RPA from resected DSBs to allow their annealing and subsequent joining
      by alt-NHEJ. Consistent with an antagonistic role for RPA during alt-NHEJ,
      inhibition of RPA1 enhances end joining and suppresses recombination. Taken
      together, our results reveal that the balance between HR and alt-NHEJ is
      controlled by opposing activities of Poltheta and RPA, providing further insight
      into the regulation of repair-pathway choice in mammalian cells.

PMID- 29058712
TI  - Molecular basis of lipid-linked oligosaccharide recognition and processing by
      bacterial oligosaccharyltransferase.
AB  - Oligosaccharyltransferase (OST) is a membrane-integral enzyme that catalyzes the
      transfer of glycans from lipid-linked oligosaccharides (LLOs) onto asparagine
      side chains, the first step in protein N-glycosylation. Here, we report the X-ray
      structure of a single-subunit OST, PglB from Campylobacter lari, trapped in an
      intermediate state bound to an acceptor peptide and a synthetic LLO analog. The
      structure reveals the role of the external loop EL5, present in all OST enzymes,
      in substrate recognition. Whereas the N-terminal half of EL5 binds LLO, the C
      terminal half interacts with the acceptor peptide. The glycan moiety of LLO must
      thread under EL5 to access the active site. Reducing EL5 mobility decreases the
      catalytic rate of OST when full-size heptasaccharide LLO is provided, but not for
      a monosaccharide-containing LLO analog. Our results define the chemistry of a
      ternary complex state, assign functional roles to conserved OST motifs, and
      provide opportunities for glycoengineering by rational design of PglB.

PMID- 29058713
TI  - Dynamic regulation of CD28 conformation and signaling by charged lipids and ions.
AB  - CD28 provides an essential costimulatory signal for T cell activation, and its
      function is critical in antitumor immunity. However, the molecular mechanism of
      CD28 transmembrane signaling remains elusive. Here we show that the conformation
      and signaling of CD28 are regulated by two counteractive charged factors, acidic
      phospholipids and Ca2+ ions. NMR spectroscopy analyses showed that acidic
      phospholipids can sequester CD28 signaling motifs within the membrane, thereby
      limiting CD28 basal signaling. T cell receptor (TCR) activation induced an
      increase in the local Ca2+ concentration around CD28, and Ca2+ directly disrupted
      CD28-lipid interaction, leading to opening and signaling of CD28. We observed
      that the TCR, Ca2+, and CD28 together form a dual-positive-feedback circuit that
      substantially amplifies T cell signaling and thus increases antigen sensitivity.
      This work unravels a new regulatory mechanism for CD28 signaling and thus
      contributes to the understanding of the dependence of costimulation signaling on
      TCR signaling and the high sensitivity of T cells.

PMID- 29058714
TI  - Predicting causal variants affecting expression by using whole-genome sequencing
      and RNA-seq from multiple human tissues.
AB  - Genetic association mapping produces statistical links between phenotypes and
      genomic regions, but identifying causal variants remains difficult. Whole-genome
      sequencing (WGS) can help by providing complete knowledge of all genetic
      variants, but it is financially prohibitive for well-powered GWAS studies. We
      performed mapping of expression quantitative trait loci (eQTLs) with WGS and RNA
      seq, and found that lead eQTL variants called with WGS were more likely to be
      causal. Through simulations, we derived properties of causal variants and used
      them to develop a method for identifying likely causal SNPs. We estimated that 25
      70% of causal variants were located in open-chromatin regions, depending on the
      tissue and experiment. Finally, we identified a set of high-confidence causal
      variants and showed that these were more enriched in GWAS associations than other
      eQTLs. Of those, we found 65 associations with GWAS traits and provide examples
      in which genes implicated by expression are functionally validated as being
      relevant for complex traits.

PMID- 29058715
TI  - Estimating the causal tissues for complex traits and diseases.
AB  - How to interpret the biological causes underlying the predisposing markers
      identified through genome-wide association studies (GWAS) remains an open
      question. One direct and powerful way to assess the genetic causality behind GWAS
      is through analysis of expression quantitative trait loci (eQTLs). Here we
      describe a new approach to estimate the tissues behind the genetic causality of a
      variety of GWAS traits, using the cis-eQTLs in 44 tissues from the Genotype
      Tissue Expression (GTEx) Consortium. We have adapted the regulatory trait
      concordance (RTC) score to measure the probability of eQTLs being active in
      multiple tissues and to calculate the probability that a GWAS-associated variant
      and an eQTL tag the same functional effect. By normalizing the GWAS-eQTL
      probabilities by the tissue-sharing estimates for eQTLs, we generate relative
      tissue-causality profiles for GWAS traits. Our approach not only implicates the
      gene likely mediating individual GWAS signals, but also highlights tissues where
      the genetic causality for an individual trait is likely manifested.

PMID- 29058717
TI  - ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ
      fibrosis.
AB  - Maladaptive wound healing responses to chronic tissue injury result in organ
      fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition
      and tissue remodeling by activated myofibroblasts, leads to loss of proper tissue
      architecture and organ function; however, the molecular mediators of
      myofibroblast activation have yet to be fully identified. Here we identify
      soluble ephrin-B2 (sEphrin-B2) as a new profibrotic mediator in lung and skin
      fibrosis. We provide molecular, functional and translational evidence that the
      ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar
      airspace after lung injury. Shedding of sEphrin-B2 promotes fibroblast chemotaxis
      and activation via EphB3 and/or EphB4 receptor signaling. We found that mice
      lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and
      that a disintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2
      sheddase in fibroblasts. ADAM10 expression is increased by transforming growth
      factor (TGF)-beta1, and ADAM10-mediated sEphrin-B2 generation is required for TGF
      beta1-induced myofibroblast activation. Pharmacological inhibition of ADAM10
      reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in
      mice. Consistent with the mouse data, ADAM10-sEphrin-B2 signaling is upregulated
      in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These
      results uncover a new molecular mechanism of tissue fibrogenesis and identify
      sEphrin-B2, its receptors EphB3 and EphB4 and ADAM10 as potential therapeutic
      targets in the treatment of fibrotic diseases.

PMID- 29058718
TI  - PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis.
AB  - Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key
      glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform
      PKM1, is methylated by co-activator-associated arginine methyltransferase 1
      (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from
      oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative
      phosphorylation depends on mitochondrial calcium concentration, which becomes
      critical for cancer cell survival when PKM2 methylation is blocked. By
      interacting with and suppressing the expression of inositol-1,4,5-trisphosphate
      receptors (InsP3Rs), methylated PKM2 inhibits the influx of calcium from the
      endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a
      competitive peptide delivered by nanoparticles perturbs the metabolic energy
      balance in cancer cells, leading to a decrease in cell proliferation, migration
      and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic
      reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation
      generates metabolic vulnerability to InsP3R-dependent mitochondrial functions.

PMID- 29058719
TI  - Synthetic hydrogels for human intestinal organoid generation and colonic wound
      repair.
AB  - In vitro differentiation of human intestinal organoids (HIOs) from pluripotent
      stem cells is an unparalleled system for creating complex, multicellular three
      dimensional structures capable of giving rise to tissue analogous to native human
      tissue. Current methods for generating HIOs rely on growth in an undefined tumour
      derived extracellular matrix (ECM), which severely limits the use of organoid
      technologies for regenerative and translational medicine. Here, we developed a
      fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated
      poly(ethylene glycol) macromer that supports robust and highly reproducible in
      vitro growth and expansion of HIOs, such that three-dimensional structures are
      never embedded in tumour-derived ECM. We also demonstrate that the hydrogel
      serves as an injection vehicle that can be delivered into injured intestinal
      mucosa resulting in HIO engraftment and improved colonic wound repair. Together,
      these studies show proof-of-concept that HIOs may be used therapeutically to
      treat intestinal injury.

PMID- 29058721
TI  - EGFR signalling controls cellular fate and pancreatic organogenesis by regulating
      apicobasal polarity.
AB  - Apicobasal polarity is known to affect epithelial morphogenesis and cell
      differentiation, but it remains unknown how these processes are mechanistically
      orchestrated. We find that ligand-specific EGFR signalling via PI(3)K and Rac1
      autonomously modulates apicobasal polarity to enforce the sequential control of
      morphogenesis and cell differentiation. Initially, EGF controls pancreatic
      tubulogenesis by negatively regulating apical polarity induction. Subsequently,
      betacellulin, working via inhibition of atypical protein kinase C (aPKC), causes
      apical domain constriction within neurogenin3+ endocrine progenitors, which
      results in reduced Notch signalling, increased neurogenin3 expression, and beta
      cell differentiation. Notably, the ligand-specific EGFR output is not driven at
      the ligand level, but seems to have evolved in response to stage-specific
      epithelial influences. The EGFR-mediated control of beta-cell differentiation via
      apical polarity is also conserved in human neurogenin3+ cells. We provide insight
      into how ligand-specific EGFR signalling coordinates epithelial morphogenesis and
      cell differentiation via apical polarity dynamics.

PMID- 29058720
TI  - The impact of cellular metabolism on chromatin dynamics and epigenetics.
AB  - The substrates used to modify nucleic acids and chromatin are affected by
      nutrient availability and the activity of metabolic pathways. Thus, cellular
      metabolism constitutes a fundamental component of chromatin status and thereby of
      genome regulation. Here we describe the biochemical and genetic principles of how
      metabolism can influence chromatin biology and epigenetics, discuss the
      functional roles of this interplay in developmental and cancer biology, and
      present future directions in this rapidly emerging area.

PMID- 29058722
TI  - Deciphering lipid structures based on platform-independent decision rules.
AB  - We achieve automated and reliable annotation of lipid species and their molecular
      structures in high-throughput data from chromatography-coupled tandem mass
      spectrometry using decision rule sets embedded in Lipid Data Analyzer (LDA;
      http://genome.tugraz.at/lda2). Using various low- and high-resolution mass
      spectrometry instruments with several collision energies, we proved the method's
      platform independence. We propose that the software's reliability, flexibility,
      and ability to identify novel lipid molecular species may now render current
      state-of-the-art lipid libraries obsolete.

PMID- 29058723
TI  - Electrophilic probes for deciphering substrate recognition by O-GlcNAc
      transferase.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential
      human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins.
      However, little is known about the mechanism with which OGT recognizes various
      protein substrates. Here we report on GlcNAc electrophilic probes (GEPs) to
      expedite the characterization of OGT-substrate recognition. Data from mass
      spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic
      assays support the application of GEPs to rapidly report the impacts of OGT
      mutations on protein substrate or sugar binding and to discover OGT residues
      crucial for protein recognition. Interestingly, we found that the same residues
      on the inner surface of the N-terminal domain contribute to OGT interactions with
      different protein substrates. By tuning reaction conditions, a GEP enables
      crosslinking of OGT with acceptor substrates in situ, affording a unique method
      to discover genuine substrates that weakly or transiently interact with OGT.
      Hence, GEPs provide new strategies to dissect OGT-substrate binding and
      recognition.

PMID- 29058726
TI  - Artificial spin ice: A ratchet made of tiny magnets.

PMID- 29058724
TI  - A CRISPR screen identifies a pathway required for paraquat-induced cell death.
AB  - Paraquat, a herbicide linked to Parkinson's disease, generates reactive oxygen
      species (ROS), which causes cell death. Because the source of paraquat-induced
      ROS production remains unknown, we conducted a CRISPR-based positive-selection
      screen to identify metabolic genes essential for paraquat-induced cell death. Our
      screen uncovered three genes, POR (cytochrome P450 oxidoreductase), ATP7A (copper
      transporter), and SLC45A4 (sucrose transporter), required for paraquat-induced
      cell death. Furthermore, our results revealed POR as the source of paraquat
      induced ROS production. Thus, our study highlights the use of functional genomic
      screens for uncovering redox biology.

PMID- 29058725
TI  - Rational design of proteins that exchange on functional timescales.
AB  - Proteins are intrinsically dynamic molecules that can exchange between multiple
      conformational states, enabling them to carry out complex molecular processes
      with extreme precision and efficiency. Attempts to design novel proteins with
      tailored functions have mostly failed to yield efficiencies matching those found
      in nature because standard methods do not allow the design of exchange between
      necessary conformational states on a functionally relevant timescale. Here we
      developed a broadly applicable computational method to engineer protein dynamics
      that we term meta-multistate design. We used this methodology to design
      spontaneous exchange between two novel conformations introduced into the global
      fold of Streptococcal protein G domain beta1. The designed proteins, named
      DANCERs, for dynamic and native conformational exchangers, are stably folded and
      switch between predicted conformational states on the millisecond timescale. The
      successful introduction of defined dynamics on functional timescales opens the
      door to new applications requiring a protein to spontaneously access multiple
      conformational states.

PMID- 29058727
TI  - Emergent dynamic chirality in a thermally driven artificial spin ratchet.
AB  - Modern nanofabrication techniques have opened the possibility to create novel
      functional materials, whose properties transcend those of their constituent
      elements. In particular, tuning the magnetostatic interactions in geometrically
      frustrated arrangements of nanoelements called artificial spin ice can lead to
      specific collective behaviour, including emergent magnetic monopoles, charge
      screening and transport, as well as magnonic response. Here, we demonstrate a
      spin-ice-based active material in which energy is converted into unidirectional
      dynamics. Using X-ray photoemission electron microscopy we show that the
      collective rotation of the average magnetization proceeds in a unique sense
      during thermal relaxation. Our simulations demonstrate that this emergent chiral
      behaviour is driven by the topology of the magnetostatic field at the edges of
      the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a
      bias field can be used to modify the sense of rotation of the average
      magnetization. This opens the possibility of implementing a magnetic Brownian
      ratchet, which may find applications in novel nanoscale devices, such as magnetic
      nanomotors, actuators, sensors or memory cells.

PMID- 29058728
TI  - Non-volatile memories: Organic memristors come of age.

PMID- 29058730
TI  - Unpicking the determinants of amide NHO[double bond, length as m-dash]C hydrogen
      bond strength with diphenylacetylene molecular balances.
AB  - Hydrogen bonding plays an essential part in dictating the properties of natural
      and synthetic materials. Secondary amides are well suited to cross-strand
      interactions through the display of both hydrogen bond donors and acceptors and
      are prevalent in polymers such as proteins, nylon, and KevlarTM. In attempting to
      measure hydrogen bond strength and to delineate the stereoelectronic components
      of the interaction, context frequently becomes vitally important. This makes
      molecular balances - systems in which direct comparison of two groups is possible
      - an appealing bottom up approach that allows the complexity of larger systems to
      be stripped away. We have previously reported a family of single molecule
      conformational switches that are responsive to diverse stimuli including Bronsted
      and Lewis acids, anions, and redox gradients. In this work we assess the ability
      of the scaffold, based on a 2,6-disubstituted diphenylacetylene, to measure
      accurately the difference in hydrogen bond strength between variously
      functionalised amides. In all of the examples investigated hydrogen bond strength
      closely correlate to measures of Bronstead acidity suggesting that the scaffold
      is well-suited as a platform for the accurate determination of bond strength in
      variously substituted systems.

PMID- 29058729
TI  - Robust resistive memory devices using solution-processable metal-coordinated azo
      aromatics.
AB  - Non-volatile memories will play a decisive role in the next generation of digital
      technology. Flash memories are currently the key player in the field, yet they
      fail to meet the commercial demands of scalability and endurance. Resistive
      memory devices, and in particular memories based on low-cost, solution
      processable and chemically tunable organic materials, are promising alternatives
      explored by the industry. However, to date, they have been lacking the
      performance and mechanistic understanding required for commercial translation.
      Here we report a resistive memory device based on a spin-coated active layer of a
      transition-metal complex, which shows high reproducibility (~350 devices), fast
      switching (<=30 ns), excellent endurance (~1012 cycles), stability (>106 s) and
      scalability (down to ~60 nm2). In situ Raman and ultraviolet-visible spectroscopy
      alongside spectroelectrochemistry and quantum chemical calculations demonstrate
      that the redox state of the ligands determines the switching states of the device
      whereas the counterions control the hysteresis. This insight may accelerate the
      technological deployment of organic resistive memories.

PMID- 29058731
TI  - Self-spreading of the wetting ridge during stick-slip on a viscoelastic surface.
AB  - Dynamic wetting behaviors on soft solids are important to interpret complex
      biological processes from cell-substrate interactions. Despite intensive research
      studies over the past half-century, the underlying mechanisms of spreading
      behaviors are not clearly understood. The most interesting feature of wetting on
      soft matter is the formation of a "wetting ridge", a surface deformation by a
      competition between elasticity and capillarity. Dynamics of the wetting ridge
      formed at the three-phase contact line underlies the dynamic wetting behaviors,
      but remains largely unexplored mostly due to limitations in indirect observation.
      Here, we directly visualize wetting ridge dynamics during continuous- and stick
      slip motions on a viscoelastic surface using X-ray microscopy. Strikingly, we
      discover that the ridge spreads spontaneously during stick and triggers contact
      line depinning (stick-to-slip transition) by changing the ridge geometry which
      weakens the contact line pinning. Finally, we clarify 'viscoelastic-braking',
      'stick-slipping', and 'stick-breaking' spreading behaviors through the ridge
      dynamics. In stick-breaking, no ridge-spreading occurs and contact line pinning
      (hysteresis) is enhanced by cusp-bending while preserving a microscopic
      equilibrium at the ridge tip. We have furthered the understanding of spreading
      behaviors on soft solids and demonstrated the value of X-ray microscopy in
      elucidating various dynamic wetting behaviors on soft solids as well as puzzling
      biological issues.

PMID- 29058732
TI  - Selenium-mediated arsenic excretion in mammals: a synchrotron-based study of
      whole-body distribution and tissue-specific chemistry.
AB  - Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking
      water, currently affects millions of people in South-East Asia and elsewhere.
      Previous animal studies revealed that the toxicity of arsenite essentially can be
      abolished if selenium is co-administered as selenite. Although subsequent studies
      have provided some insight into the biomolecular basis of this striking
      antagonism, many details of the biochemical pathways that ultimately result in
      the detoxification and excretion of arsenic using selenium supplements have yet
      to be thoroughly studied. To this end and in conjunction with the recent Phase
      III clinical trial "Selenium in the Treatment of Arsenic Toxicity and Cancers",
      we have applied synchrotron X-ray techniques to elucidate the mechanisms of this
      arsenic-selenium antagonism at the tissue and organ levels using an animal model.
      X-ray fluorescence imaging (XFI) of cryo-dried whole-body sections of laboratory
      hamsters that had been injected with arsenite, selenite, or both chemical
      species, provided insight into the distribution of both metalloids 30 minutes
      after treatment. Co-treated animals showed strong co-localization of arsenic and
      selenium in the liver, gall bladder and small intestine. X-ray absorption
      spectroscopy (XAS) of freshly frozen organs of co-treated animals revealed the
      presence in liver tissues of the seleno bis-(S-glutathionyl) arsinium ion, which
      was rapidly excreted via bile into the intestinal tract. These results firmly
      support the previously postulated hepatobiliary excretion of the seleno bis-(S
      glutathionyl) arsinium ion by providing the first data pertaining to organs of
      whole animals.

PMID- 29058733
TI  - Visible-light-mediated direct difluoromethylation of alkynoates: synthesis of 3
      difluoromethylated coumarins.
AB  - A photoredox-catalyzed direct difluoromethylation of alkynoates has been
      developed. A well-designed photoredox system induces a single-step,
      regioselective installation of CF2H onto alkynes. Difluoromethyl sulfone was used
      as an easy to handle CF2H radical source to afford the desired 3
      difluoromethylated coumarins in moderate to good yields via a radical-triggered
      tandem difluoromethylation/5-exo cyclization/ester migration process.

PMID- 29058736
TI  - Real-time visualization and sub-diffraction limit localization of nanometer-scale
      pore formation by dielectric breakdown.
AB  - Herein, we introduce synchronous, real-time, electro-optical monitoring of
      nanopore formation by DB. Using the same principle as sub-diffraction microscopy,
      our nanopore localization platform based on wide-field microscopy and calcium
      indicators provides nanoscale sensitivity. This enables us to establish critical
      limitations of the fabrication process and improve its reliability. In
      particular, we find that under certain conditions, multiple nanopores may form
      and that nanopores may preferentially localize at the membrane junction, either
      of which potentially render nanopore sensing ineffective. As the breakdown
      parameters of silicon materials are highly manufacturer-specific, we anticipate
      that our visualization platform will enable users to easily optimize DB
      fabrication according to specific needs. Furthermore, our technique furthers the
      applicability of DB to more complicated architectures, such as membranes with
      selectively thinned regions and plasmonic nanowells.

PMID- 29058737
TI  - On-demand electrically controlled drug release from resorbable nanocomposite
      films.
AB  - Electroresponsive materials are promising carriers for developing drug delivery
      systems (DDSs) with excellent spatial, temporal, and dosage control over drug
      release. Current electroresponsive systems use high voltages (2-25 V), are not
      bioresorbable, or use materials with unknown long-term biocompatibility. We
      report here a nanocomposite film that is resorbable, electroresponsive at low
      voltages (<-2 V), and composed of entirely FDA-approved materials. Our DDS is
      based on poly(methyl methacrylate-co-methacrylic acid), commercially marketed as
      Eudragit S100 (EGT), which has pH-dependent aqueous solubility. Nanometric films
      of drug-loaded EGT were designed, synthesized, and coated with a protective layer
      of chitosan. We hypothesized that electric stimuli would cause local pH changes
      on the working electrode, leading to pH-responsive dissolution of EGT with
      concomitant drug release. Our results confirm that local pH changes impart
      electroresponsive release behavior to the films. Furthermore, drug release scales
      linearly with voltage, current, and time. The generalizability of the system is
      shown through the release of several molecules of varying hydrophobicity, pKa,
      and size, including fluorescein (free acid and sodium salt), curcumin, meloxicam,
      and glucagon. The ability to modulate drug release with the applied stimulus can
      be utilized to design minimally invasive drug delivery devices based on
      bioresorbable electronics. Such devices would allow for personalized medicine in
      the treatment of chronic diseases.

PMID- 29058738
TI  - Surface potential and morphology mapping to investigate analyte adsorption
      effects on surface enhanced Raman scattering (SERS).
AB  - We demonstrate the power of Kelvin probe force microscopy (KPFM) in enabling a
      comprehensive study of enhancement mechanisms of surface enhanced Raman
      scattering (SERS) through the correlation of surface electrical and topographical
      effects. Local electric fields generated on Au/ZnO nanohybrid films impact
      analyte adsorption, while roughness is linked to hotspot generation. Optimizing
      the interplay between these two effects yields SERS enhancement factors (EFs) of
      106, enabling ppb detection of polycyclic aromatic hydrocarbons (PAHs) in water.

PMID- 29058740
TI  - NIR-absorbing dye functionalized hollow mesoporous silica nanoparticles for
      combined photothermal-chemotherapy.
AB  - Multifunctional hollow mesoporous silica nanoparticles were constructed by
      firstly loading with doxorubicin and then capping with disulfide linked beta
      cyclodextrin followed by complexation with adamantane functionalized indocyanine
      dye, showing improved anticancer efficacy through combined photothermal
      chemotherapy.

PMID- 29058739
TI  - The nucleosomal surface is the main target of histone ADP-ribosylation in
      response to DNA damage.
AB  - ADP-ribosylation is a protein post-translational modification catalyzed by ADP
      ribose transferases (ARTs). ART activity is critical in mediating many cellular
      processes, and is required for DNA damage repair. All five histone proteins are
      extensively ADP-ribosylated by ARTs upon induction of DNA damage. However, how
      these modifications aid in repair processes is largely unknown, primarily due to
      lack of knowledge about where they site-specifically occur on histones. Here, we
      conduct a comprehensive analysis of histone Asp/Glu ADP-ribosylation sites upon
      DNA damage induced by dimethyl sulfate (DMS). We also demonstrate that incubation
      of cell nuclei with NAD+, as has been done previously in the literature, leads to
      spurious ADP-ribosylation levels of histone proteins. Altogether, we were able to
      identify 30 modification sites, 20 of which are novel. We also quantify the
      abundance of these modification sites during the course of DNA damage insult to
      identify which sites are critical for mediating repair. We found that every
      quantifiable site increases in abundance over time and that each identified ADP
      ribosylation site is located on the surface of the nucleosome. Together, the data
      suggest specific Asp/Glu residues are unlikely to be critical for DNA damage
      repair and rather that this process is likely dependent on ADP-ribosylation of
      the nucleosomal surface in general.

PMID- 29058741
TI  - Electronic properties of single-layer tungsten disulfide on epitaxial graphene on
      silicon carbide.
AB  - This work reports an electronic and micro-structural study of an appealing system
      for optoelectronics: tungsten disulfide (WS2) on epitaxial graphene (EG) on
      SiC(0001). The WS2 is grown via chemical vapor deposition (CVD) onto the EG. Low
      energy electron diffraction (LEED) measurements assign the zero-degree
      orientation as the preferential azimuthal alignment for WS2/EG. The valence-band
      (VB) structure emerging from this alignment is investigated by means of
      photoelectron spectroscopy measurements, with both high space and energy
      resolution. We find that the spin-orbit splitting of monolayer WS2 on graphene is
      of 462 meV, larger than what is reported to date for other substrates. We
      determine the value of the work function for the WS2/EG to be 4.5 +/- 0.1 eV. A
      large shift of the WS2 VB maximum is observed as well, due to the lowering of the
      WS2 work function caused by the donor-like interfacial states of EG. Density
      functional theory (DFT) calculations carried out on a coincidence supercell
      confirm the experimental band structure to an excellent degree. X-ray
      photoemission electron microscopy (XPEEM) measurements performed on single WS2
      crystals confirm the van der Waals nature of the interface coupling between the
      two layers. In virtue of its band alignment and large spin-orbit splitting, this
      system gains strong appeal for optical spin-injection experiments and opto
      spintronic applications in general.

PMID- 29058742
TI  - A pyrene-functionalized foldamer: structural impact and recognition properties
      supported by donor-acceptor interactions.
AB  - An electroactive and luminescent foldamer based on an oligopyridine
      biscarboxamide skeleton was synthesized and characterised. Its conformation in
      the solid state proved to be strongly affected by the peripheral pyrene units.
      The latter also endow the target derivative with recognition abilities toward
      electron-withdrawing molecules, which allow tuning of the spectroscopic
      properties of the foldamer.

PMID- 29058743
TI  - A novel multimode sensor showing cation-dependent fluorescence colour.
AB  - A novel sensor, 4-[2-(9-anthryl)ethynyl]-1,10-phenanthroline (1), exhibits highly
      intense fluorescent in the wavelength region of 440-600 nm (maximum wavelength
      (lambdaf) = 470 nm) with the quantum yield (Phif) and lifetime (tauf) being 0.90
      and 4.2 ns, respectively, in CH3CN at 298 K. In the presence of a divalent cation
      (M2+ = Ba2+, Ca2+, Mg2+, or Zn2+) in CH3CN, sensor 1 can tightly bind M2+ and
      shows intense fluorescent (Phif = 0.90-0.19, tauf = 2.1-6.9 ns) with the color
      being dependent on the nature of M2+ (lambdaf = 514-584 nm). The results
      demonstrate that a single fluorescent sensor 1 is capable of simultaneous
      identification and quantitation of M2+ based on lambdaf and the fluorescent
      intensity (Phif), respectively. The fluorescence maximum energy of the [1-M2+]
      complex is shown to correlate linearly with the pKa value of M2+. The
      spectroscopic and photophysical properties of sensor 1 in the absence and
      presence of M2+ are also discussed.

PMID- 29058716
TI  - Identification of ten variants associated with risk of estrogen-receptor-negative
      breast cancer.
AB  - Most common breast cancer susceptibility variants have been identified through
      genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)
      positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594
      controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer),
      all of European origin. We identified independent associations at P < 5 * 10-8
      with ten variants at nine new loci. At P < 0.05, we replicated associations with
      10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation
      carrier GWAS and observed consistent associations with ER-negative disease for
      105 susceptibility variants identified by other studies. These 125 variants
      explain approximately 16% of the familial risk of this breast cancer subtype.
      There was high genetic correlation (0.72) between risk of ER-negative breast
      cancer and breast cancer risk for BRCA1 mutation carriers. These findings may
      lead to improved risk prediction and inform further fine-mapping and functional
      work to better understand the biological basis of ER-negative breast cancer.

PMID- 29058744
TI  - Hybrid deterministic/stochastic simulation of complex biochemical systems.
AB  - In a biological cell, cellular functions and the genetic regulatory apparatus are
      implemented and controlled by complex networks of chemical reactions involving
      genes, proteins, and enzymes. Accurate computational models are indispensable
      means for understanding the mechanisms behind the evolution of a complex system,
      not always explored with wet lab experiments. To serve their purpose,
      computational models, however, should be able to describe and simulate the
      complexity of a biological system in many of its aspects. Moreover, it should be
      implemented by efficient algorithms requiring the shortest possible execution
      time, to avoid enlarging excessively the time elapsing between data analysis and
      any subsequent experiment. Besides the features of their topological structure,
      the complexity of biological networks also refers to their dynamics, that is
      often non-linear and stiff. The stiffness is due to the presence of molecular
      species whose abundance fluctuates by many orders of magnitude. A fully
      stochastic simulation of a stiff system is computationally time-expensive. On the
      other hand, continuous models are less costly, but they fail to capture the
      stochastic behaviour of small populations of molecular species. We introduce a
      new efficient hybrid stochastic-deterministic computational model and the
      software tool MoBioS (MOlecular Biology Simulator) implementing it. The
      mathematical model of MoBioS uses continuous differential equations to describe
      the deterministic reactions and a Gillespie-like algorithm to describe the
      stochastic ones. Unlike the majority of current hybrid methods, the MoBioS
      algorithm divides the reactions' set into fast reactions, moderate reactions, and
      slow reactions and implements a hysteresis switching between the stochastic model
      and the deterministic model. Fast reactions are approximated as continuous
      deterministic processes and modelled by deterministic rate equations. Moderate
      reactions are those whose reaction waiting time is greater than the fast reaction
      waiting time but smaller than the slow reaction waiting time. A moderate reaction
      is approximated as a stochastic (deterministic) process if it was classified as a
      stochastic (deterministic) process at the time at which it crosses the threshold
      of low (high) waiting time. A Gillespie First Reaction Method is implemented to
      select and execute the slow reactions. The performances of MoBios were tested on
      a typical example of hybrid dynamics: that is the DNA transcription regulation.
      The simulated dynamic profile of the reagents' abundance and the estimate of the
      error introduced by the fully deterministic approach were used to evaluate the
      consistency of the computational model and that of the software tool.

PMID- 29058745
TI  - Quantum confinement induced ultra-high intensity interfacial radiative
      recombination in nanolaminates.
AB  - Al2O3/ZnO, Al2O3/TiO2, TiO2/ZnO and MgO/ZnO nanolaminates (NLs) were prepared
      using atomic layer deposition to explore the dependence of luminescence
      characterization on the sublayer width and constituents. When the ZnO sublayer
      width is larger than the Bohr radius in Al2O3/ZnO NLs, the UV luminescence
      arising from ZnO is reduced and even quenched with decreasing the ZnO width due
      to the nonradiative recombination (NR) caused by the existence of interface
      states, while for the ZnO width smaller than the Bohr radius, a visible
      luminescence rather than UV emission is observed and further enhanced with
      decreasing the ZnO width. It is also found that the visible luminescence needs a
      certain width of Al2O3 and is extinguished by the replacement of Al2O3 with TiO2.
      A theoretical model based on the configuration coordination and quantum
      confinement effect is proposed to understand the physical origin underlying the
      intriguing optical behaviour. The mechanism has generality and is applicable for
      other NLs as well, such as Al2O3/TiO2 and MgO/ZnO NLs with ultra-thin sublayers
      in which similar luminescence enhancements are also observed. This work may
      provide a promising approach for realizing high performance luminescence with
      various wavelengths for electro- and photo-luminescence applications in NLs.

PMID- 29058746
TI  - NHC-catalyzed regiodivergent syntheses of difunctionalized 3-pyrazolidinones from
      alpha-bromoenal and monosubstituted hydrazine.
AB  - A formal [3 + 2] annulation of alpha-bromoenal with monosubstituted hydrazine
      could give 1,5 or 2,5-difunctionalized 3-pyrazolidinone regiodivergently by
      tuning the structure of the N-Heterocyclic Carbene (NHC) catalyst. Moderate to
      high yields, mild reaction conditions, good regioselectivity and potential
      biological significance of the final product have made this protocol attractive
      for the assembly of 3-pyrazolidinone.

PMID- 29058747
TI  - Cobalt and nickel impair DNA metabolism by the oxidative stress independent
      pathway.
AB  - The oxidative stress that evolves under cobalt and nickel exposure is thought to
      exert toxicity, though the exact routes of such metal poisoning remain ambiguous.
      We revisited the metal toxicity in Escherichia coli to show that cobalt and
      nickel exposure at levels as low as 0.5 and 1 mM, respectively, visibly inhibits
      growth. We also observed that acidic conditions aggravated, while alkaline
      conditions alleviated the metal toxicity. Besides, 1 mM manganese, which is non
      cytotoxic, as judged by the growth of E. coli, synergistically elevated cobalt
      and nickel stress. However, the metal toxicity did not lead to oxidative stress
      in E. coli. On the other hand, we show that cobalt and nickel, but not manganese,
      reduced the rate of DNA replication to 50% within 2 hours. Interestingly, the
      metal ions promoted DNA double-strand breaks but did not induce SOS repair
      pathways, indicating that the metal ions could block SOS induction. To test this,
      we show that cobalt and nickel, but not manganese, suppressed the nalidixic acid
      induced SOS response. Finally, using an in vitro assay system, we demonstrated
      that cobalt and nickel inhibit RecBCD function, which is essential for SOS
      induction. Therefore, our data indicate that cobalt and nickel affect DNA
      replication, damage DNA, and inhibit the SOS repair pathway to exert toxicity.

PMID- 29058748
TI  - Experimental and mechanistic insights into copper(ii)-dioxygen catalyzed
      oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine and its derivatives.
AB  - A di-(2-pyridylmethyl)phenylamine ((PyCH2)2NPh) supported Cu(ii)/O2 catalytic
      system was explored with the synthesis of pyridylmethyl-based compounds of
      carboxylate (PyCOOH), amide (PyC(O)NHPh), and imine (PyCH[double bond, length as
      m-dash]NPh) from the oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine
      (PyCH2NHPh) and its derivatives, by means of controlling the addition of a base
      and/or water to the reaction system under a dioxygen atmosphere at room
      temperature. Experimental studies showed that the imine and amide species could
      be precursors in succession in the way to the final oxidation state of
      carboxylates. A cyclic catalytic mechanism was proposed including the base
      triggered C-H bond activation of the 2-pyridylmethyl group (PyCH2-) and the
      intermolecular Cu-OOH alpha-hydrogen atom abstraction from the coordinated imine
      substrate (PyCH[double bond, length as m-dash]NPh).

PMID- 29058750
TI  - The one-pot synthesis of quinolines via Co(iii)-catalyzed C-H
      activation/carbonylation/cyclization of anilines.
AB  - We herein disclose a novel Co(iii)-catalyzed C-H
      activation/carbonylation/cyclization of anilines with ketones using
      paraformaldehyde as the carbonyl source, giving direct access to diverse
      quinolines with broad functional group tolerance and in good to excellent yields.
      Moreover, exclusive site-/region-selectivity was observed in this versatile
      transformation.

PMID- 29058752
TI  - Anionic ribose related species explored through PES experiments, DFT
      calculations, and through comparison with anionic fructose species.
AB  - Ribose related species, (ribose-H)- and (ribose-H2O)-, are investigated through
      anion photoelectron spectroscopy (PES) combined with density functional theory
      (DFT) calculations. Their vertical detachment energies (VDEs) are experimentally
      determined and their anionic structures with positional and conformational
      isomers are definitively assigned. The ribose- parent anion is not detected in
      the present experiments. (ribose-H)- and (ribose-H2O)- anions can be accessed as
      the characteristic fragmentation ions of the parent species. Generation of
      (ribose-H)- through the matrix assisted laser desorption ionization (MALDI)
      process is sample desorption substrate dependent, while generation of (ribose
      H2O)- is independent of a wide range of desorption substrates. Both
      conformational and positional isomers of (ribose-H)- are identified in the gas
      phase. Two types of positional isomers of (ribose-H2O)- (both from open chain
      structures) are assigned to contribute to two different components of the
      observed PES feature. The dehydration process can be thermodynamically accessed
      through both the parent anion and the neutral. A comparison between the PES and
      DFT results of ribose and fructose leads to the general conclusions: (1) ribose-
      open chain structures are more likely to lose hydrogen from C atoms than fructose
      open chain structures, especially from (2)C and (4)C positions; (2) ribofuranose
      has a relatively higher propensity for loss of H than does fructofuranose- in
      our MALDI/ablation process; and (3) the ribofuranose- anion has lower
      decomposition probability through loss of water compared to the fructofuranose-
      anion.

PMID- 29058753
TI  - N-Heterocyclic carbene-induced transmethylation in tungsten imido alkylidene
      bistriflates: unexpected formation of an N-heterocyclic olefin complex.
AB  - The reaction of [W(N-2,6-iPr2C6H3)(CHCMe2Ph)(OTf)2(DME)] (DME = 1,2
      dimethoxyethane, OTf = CF3SO3) with the N-heterocyclic carbene (NHC) 1,3
      bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene (IMesH2) leads to DME activation
      followed by transmethylation and in due consequence to the formation of the N
      heterocyclic olefin complex [W(N-2,6-iPr2C6H3)(CHCMe2Ph)(OTf)2(IMesH2CH2)] along
      with [W(N-2,6-iPr2C6H3)(CHCMe2Ph)(OTf)(IMesH2)(kappa2-O(CH2)2OMe)], [1,3
      bis(2,4,6-trimethylphenyl)-2-methylimidazolidinium+ (OTf-)] and [1,3-bis(2,4,6
      trimethylphenyl)-2-H-imidazolidinium+ (OTf-)]. A reaction pathway is proposed and
      confirmed by the use of 13C-labelled compounds; structures of the products were
      verified by NMR and/or single-crystal X-ray analysis.

PMID- 29058754
TI  - Partial Resurfacing for Humeral Head Defects Associated With Recurrent Shoulder
      Instability.
AB  - Recurrent traumatic shoulder instability is a complex clinical entity that
      commonly affects young, active patients. Humeral head defects are frequently
      associated with this condition, but specific treatment to stabilize the shoulder
      is rarely needed. Management options for defects of the humeral head that do
      necessitate treatment carry various risks and disadvantages, including the need
      for bone or soft tissue healing, complications related to hardware, and loss of
      motion. Partial prosthetic resurfacing has been reported as a treatment option.
      The current study retrospectively reviewed a cohort of patients with recurrent or
      locked anterior and posterior instability who underwent partial prosthetic
      humeral head resurfacing for significant Hill-Sachs and reverse Hill-Sachs
      lesions. At an average of 36.4 months after the index procedure, 16 patients were
      contacted by mail and telephone. Of the study group, 13 patients underwent
      partial resurfacing for anterior instability and 3 patients underwent partial re
      surfacing for posterior instability. No patient had a repeat dislocation. In
      addition, 77% of patients in the anterior instability cohort and all of the
      patients in the posterior instability cohort returned to their full preinjury
      activity level. For the anterior instability cohort, significant improvements
      from preoperatively to final follow-up occurred for mean Musculoskeletal Review
      of System score (4.54, P<.0001) and Short Form-12 physical component score (9.52,
      P=.002). For the combined cohort, the Penn Shoulder Score improved by 36.4 points
      (P=.059). This study showed the effectiveness of partial humeral head resurfacing
      for preventing redislocation for patients with significant Hill-Sachs and reverse
      Hill-Sachs lesions. [Orthopedics. 2017; 40(6):e996-e1003.].

PMID- 29058755
TI  - Functional Outcomes for Nonoperatively Treated Proximal Fifth Metatarsal
      Fractures.
AB  - Fractures of the proximal fifth metatarsal are relatively common and can be
      treated with a variety of treatment modalities. The goals of the current study
      were to answer the following questions: (1) Is there a difference in functional
      outcomes with different nonoperative treatment modalities for avulsion and Jones
      fractures? (2) What is the long-term functional impairment? This study included
      53 patients who were treated for proximal fifth metatarsal fracture at 1
      university health care system between 2004 and 2013. Treatment methods included
      shoe modification, cast, and boot. Patients completed a telephone questionnaire
      that included selected questions from the Musculoskeletal Outcomes Data
      Evaluation and Management System (MODEMS). Treatment groups were stratified as
      shoe modification or immobilization, and the results of the MODEMS survey were
      compared. At most recent follow-up, no significant difference was found between
      the 2 patient groups (P=.062) for self-reported effects of the injury on work and
      quality of life. No significant difference was found for frequency of use of pain
      medication (P=.157), patient satisfaction with current symptoms (P=.633),
      ambulatory status (P=.281), or pain level with strenuous activity (P=.772). Obese
      patients were more likely to have severe pain with strenuous activity (P=.015).
      Most (87%) patients were able to ambulate without the need for assistive devices.
      Of the study patients, 79% could wear dress shoes, excluding high heels,
      comfortably. The findings showed that patients who were treated with a variety of
      nonoperative methods for closed proximal fifth metatarsal fracture had acceptable
      functional outcomes, regardless of treatment method. [Orthopedics. 2017;
      40(6):e1030-e1035.].

PMID- 29058756
TI  - Low Incidence of Neurovascular Complications After Placement of Proximal Tibial
      Traction Pins.
AB  - Skeletal tibial traction is a temporizing measure used preoperatively for femoral
      fractures to improve the length and alignment of the limb and provide pain
      relief. The goal of this study was to identify possible neurovascular morbidity
      associated with the use of bedside skeletal tibial traction to treat femur
      fractures. All femoral fractures treated with proximal tibial traction during a
      10-year period at an urban level I trauma center were retrospectively reviewed.
      The medical record was reviewed to determine whether a pin-related complication
      had occurred. Records also were reviewed to identify ipsilateral multi
      ligamentous knee injuries that were not diagnosed until after the application of
      traction. In total, 303 proximal tibial traction pins were placed. A total of 7
      (2.3%; 95% confidence interval, 0.60%-4.0%) pin-related neurologic complications
      and zero vascular complications were noted. All complications involved motor
      and/or sensory deficits in the distribution of the peroneal nerve. Of the 7
      complications, 6 resolved fully after surgery and removal of the pin. After
      traction placement, 6 (2.0%) ipsilateral multiligamentous knee injuries were
      diagnosed. None of these patients had a neurovascular complication. This study
      suggests that bedside placement of proximal tibial traction for femoral fractures
      is associated with a low incidence of neurovascular complications and that
      traction can be safely placed at the bedside by residents. A thorough
      neurovascular examination should be performed before insertion, and care should
      be taken to identify the proper starting point and reduce soft tissue trauma
      during pin placement. [Orthopedics. 2017; 40(6):e1004-e1008.].

PMID- 29058757
TI  - Outcomes and Predictors of Success for Arthroscopic Lysis of Adhesions for the
      Stiff Total Knee Arthroplasty.
AB  - A stiff total knee arthroplasty (TKA) can manifest as pain and decreased range of
      motion (ROM). When conservative management including physical therapy and
      manipulation under anesthesia fails, arthroscopic lysis of adhesions (LOA) is
      frequently pursued. The authors examined the efficacy of LOA for the stiff TKA.
      They retrospectively reviewed the records of 18 patients who underwent LOA for
      stiff TKA between April 2013 and June 2016 and who failed to meet 90 degrees  ROM
      at 6 weeks postoperatively. They recorded patient demographics, ROM prior to TKA,
      and incidence of manipulation under anesthesia between initial TKA and LOA as
      well as pre- and postoperative outcomes of ROM, pain, and Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) scores. The mean time from TKA
      to LOA was 117 days, with a mean follow-up of 449 days. Mean improvements in ROM
      flexion contracture, flexion, and arc were 6.11 degrees  (P<.05), 29.45 degrees 
      (P<.001), and 35.56 degrees  (P<.001), respectively. Range of motion improved for
      17 of 18 patients. The WOMAC was completed by 15 of 18 patients, with a mean
      improvement in scores of 32.23% (P<.001); all 15 patients with available WOMAC
      scores improved. Pain score improved by a mean of 2.17 (P<.001), with 14 of 18
      patients reporting decreased pain. Improvements in flexion contracture, flexion,
      ROM arc, WOMAC scores, and pain were all statistically significant (P<.05). Age,
      weight, body mass index, and time to LOA were found to be statistically
      significant predictors of outcome. Finally, pre-TKA and pre-LOA ROM parameters
      were found to be statistically significant predictors of post-LOA ROM outcomes.
      [Orthopedics. 2017; 40(6):e1062-e1068.].

PMID- 29058758
TI  - Features of 921 Patients With Spinal Tuberculosis: A 16-Year Investigation of a
      General Hospital in Southwest China.
AB  - Southwest China has a high burden of spinal tuberculosis (TB). Few large case
      studies of spinal TB in southwest China have been conducted. This study
      investigated the features of 921 patients who were treated for spinal TB at a
      general hospital in southwest China between 2001 and 2016. Demographic data,
      clinical data, laboratory data, imaging findings, treatment methods, and outcomes
      of patients who were admitted to the hospital for spinal TB were reviewed
      retrospectively. The annual incidence of spinal TB increased throughout the study
      period. The greatest number of patients were 41 to 50 years old (22.04%). Local
      pain was the most common symptom (97.8%). A significant difference in the
      duration of symptoms was observed between rural populations (28.40 months) and
      urban populations (10.17 months) (P=.041). Of the patients, 32.68% had a normal
      erythrocyte sedimentation rate and 25.84% had a normal C-reactive protein level.
      The lumbar spine was the most commonly involved spinal site (44.77%), followed by
      the thoracic spine (43.60%). All of the patients underwent chemotherapy, and
      77.10% of patients underwent surgery. Most of the patients were cured, with the
      exception of 2.19% of patients who discontinued chemotherapy after early
      improvement of clinical status. Spinal TB is still a major public health problem
      in southwest China. Chemotherapy and surgery can yield satisfactory outcomes with
      timely diagnosis and long-term treatment. It is urgent to increase the attention
      paid to spinal TB and improve knowledge of this disease among the general public,
      especially in southwest China. [Orthopedics. 2017; 40(6):e1017-e1023.].

PMID- 29058759
TI  - Implant Failure Rates and Cost Analysis of Contoured Locking Versus Conventional
      Plate Fixation of Distal Fibula Fractures.
AB  - The authors analyzed 330 consecutive Weber B distal fibula fractures that
      occurred during a 3-year period and were treated with either a contoured locking
      plate or a conventional one-third tubular plate to compare the cost and failure
      rates of the 2 constructs. The primary outcomes were failure of the distal
      fibular implant and loss of reduction. Secondary outcomes were surgical wound
      infection requiring surgical debridement and/or removal of the fibular implant,
      and removal of the fibular plate for persistent implant-related symptoms. No
      failure of the fibular plates or distal fibular fixation occurred in either
      group. A total of 5 patients required surgical revision of syndesmotic fixation
      within 4 weeks of the index surgery. Of these patients, 1 was in the contoured
      locking plate group and 4 were in the one-third tubular plate group (P=.610). The
      rate of deep infection requiring surgical debridement and/or implant removal was
      6.2% in the contoured locking plate group and 1.4% in the one-third tubular plate
      group (P=.017). The rate of lateral implant removal for either infection or
      symptomatic implant was 9.3% in the contoured locking plate group and 2.3% in the
      one-third tubular plate group (P=.005). A typical contoured locking plate
      construct costs $800 more than a comparable one-third tubular plate construct.
      Based on a calculated estimate of 60,000 locking plates used annually in the
      United States, this difference translates to a potential avoided annual cost of
      $50 million nationally. This study demonstrates that it is possible to treat
      Weber B distal fibula fractures with one-third tubular plates at a substantially
      lower cost than that of contoured locking plates without increasing
      complications. [Orthopedics. 2017; 40(6):e1024-e1029.].

PMID- 29058760
TI  - Identification of novel inhibitors against UDP-galactopyranose mutase to combat
      leishmaniasis.
AB  - Leishmania, a protozoan parasite that causes leishmaniasis, affects 1-2 million
      people every year worldwide. Leishmaniasis is a vector born disease and
      characterized by a diverse group of clinical syndromes. Current treatment is
      limited because of drug resistance, high cost, poor safety, and low efficacy. The
      urgent need for potent agents against Leishmania has led to significant advances
      in the development of novel antileishmanial drugs. beta-galactofuranose (beta
      Galf) is an important component of Leishmanial cell surface matrix and plays a
      critical role in the pathogenesis of parasite. UDP-galactopyranose mutase (UGM)
      converts UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf) which
      acts as the precursor for beta-Galf synthesis. Due to its absence in human, this
      enzyme is selected as the potential target in search of new antileishmanial
      drugs. Three dimensional protein structure model of Leishmania major UGM (LmUGM)
      has been homology modeled using Trypanosoma cruzi UGM (TcUGM) as a template. The
      stereochemistry was validated further. We selected already reported active
      compounds from PubChem database to target the LmUGM. Three compounds (6064500,
      44570814, and 6158954) among the top hit occupied the UDP binding site of UGM
      suggested to work as a possible inhibitor for it. In vitro antileishmanial
      activity assay was performed with the top ranked inhibitor, 6064500. The 6064500
      molecule has inhibited the growth of Leishmania donovani promastigotes
      significantly. Further, at similar concentrations it has exhibited significantly
      lesser toxicity than standard drug miltefosine hydrate in mammalian cells.

PMID- 29058761
TI  - c-Abl tyrosine kinase regulates neutrophil crawling behavior under fluid shear
      stress via Rac/PAK/LIMK/cofilin signaling axis.
AB  - The excessive recruitment and improper activation of polymorphonuclear
      neutrophils (PMNs) often induces serious injury of host tissues, leading to
      inflammatory disorders. Therefore, to understand the molecular mechanism on
      neutrophil recruitment possesses essential pathological and physiological
      importance. In this study, we found that physiological shear stress induces c-Abl
      kinase activation in neutrophils, and c-Abl kinase inhibitor impaired neutrophil
      crawling behavior on ICAM-1. We further identified Vav1 was a downstream effector
      phosphorylated at Y174 and Y267. Once activated, c-Abl kinase regulated the
      activity of Vav1, which further affected Rac1/PAK1/LIMK1/cofilin signaling
      pathway. Here, we demonstrate a novel signaling function and critical role of c
      Abl kinase during neutrophil crawling under physiological shear by regulating
      Vav1. These findings provide a promising treatment strategy for inflammation
      related disease by inactivation of c-Abl kinase to restrict neutrophil
      recruitment.

PMID- 29058762
TI  - Planned caesarean section versus planned vaginal birth for severe pre-eclampsia.
AB  - BACKGROUND: Pre-eclampsia is a very frequent complication of pregnancy, and
      anticipation of birth is often necessary. However, the best mode of giving birth
      remains to be established, although observational studies suggest better maternal
      and perinatal outcomes with vaginal birth. OBJECTIVES: To assess the effects of a
      policy of planned caesarean section versus planned vaginal birth for women with
      severe pre-eclampsia on mortality and morbidity for mother and baby. SEARCH
      METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register,
      ClinicalTrials.gov, the World Health Organization (WHO) International Clinical
      Trials Registry Platform (ICTRP) (6 September 2017) and reference lists of
      retrieved studies. SELECTION CRITERIA: We planned to include all randomised
      trials of planned caesarean section versus planned vaginal birth for pregnant
      women with severe pre-eclampsia. Quasi-randomised and non-randomised studies are
      not eligible for inclusion in this review.The focus of this review is severe pre
      eclampsia; studies of planned caesarean section versus planned vaginal birth in
      pregnant women with eclampsia are not eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: We identified no studies that met the inclusion criteria. We excluded
      two studies. MAIN RESULTS: There are no included studies in this review. AUTHORS'
      CONCLUSIONS: There is a lack of robust evidence from randomised controlled trials
      that can inform practice regarding planned caesarean section versus planned
      vaginal birth for women with severe pre-eclampsia. There is a need for high
      quality randomised controlled trials to assess the short- and long-term effects
      of caesarean section and vaginal birth for these women and their babies.

PMID- 29058763
TI  - S14G-humanin alleviates insulin resistance and increases autophagy in neurons of
      APP/PS1 transgenic mouse.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized
      by Abeta plaque deposition in the brain, which is related to the disorder of
      autophagosome maturation, transport, and formation of autolysosome. Notably,
      abnormal insulin signaling is connected with cognitive dysfunction in AD. In this
      study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism
      by which S14G-humanin (HNG) improved autophagy and insulin signaling in AD brain.
      Immunohistochemistry was used to determine the levels of mTOR and Abeta
      deposition, and Western blot analysis was used to determine IRS-1, IRS-1 pSEr636,
      ULK1, p62, LC3 I/LC3 II protein levels. Our results demonstrated that HNG could
      improve the learning ability and memory in APP/PS1 transgenic mice, possibly
      through decreasing IRS-1 Ser636 phosphorylation and mTOR protein expression in
      the hippocampus, thus improving insulin resistance in the brain. In addition, HNG
      increased ULK1 expression, decreased p62 and LC3 I/LC3 II protein levels, thus
      enhancing autophagy and decreasing Abeta deposition in the brain. Taken together,
      our results suggest that through the regulation of IRS-1/mTOR insulin signaling
      in the hippocampus, HNG increases the activity of autophagy and decreases Abeta
      deposition in the brain, and improves learning ability and memory of AD mice.

PMID- 29058765
TI  - Cumulative effects of wildfires on forest dynamics in the eastern Cascade
      Mountains, USA.
AB  - Wildfires pose a unique challenge to conservation in fire-prone regions, yet few
      studies quantify the cumulative effects of wildfires on forest dynamics (i.e.,
      changes in structural conditions) across landscape and regional scales. We
      assessed the contribution of wildfire to forest dynamics in the eastern Cascade
      Mountains, USA from 1985 to 2010 using imputed maps of forest structure (i.e.,
      tree size and canopy cover) and remotely sensed burn severity maps. We addressed
      three questions: (1) How do dynamics differ between the region as a whole and the
      unburned portion of the region? (2) How do dynamics vary among vegetation zones
      differing in biophysical setting and historical fire frequency? (3) How have
      forest structural conditions changed in a network of late successional reserves
      (LSRs)? Wildfires affected 10% of forests in the region, but the cumulative
      effects at this scale were primarily slight losses of closed-canopy conditions
      and slight gains in open-canopy conditions. In the unburned portion of the region
      (the remaining 90%), closed-canopy conditions primarily increased despite other
      concurrent disturbances (e.g., harvest, insects). Although the effects of fire
      were largely dampened at the regional scale, landscape scale dynamics were far
      more variable. The warm ponderosa pine and cool mixed conifer zones experienced
      less fire than the region as a whole despite experiencing the most frequent fire
      historically. Open-canopy conditions increased slightly in the mixed conifer
      zone, but declined across the ponderosa pine zone even with wildfires. Wildfires
      burned 30% of the cold subalpine zone, which experienced the greatest increase in
      open-canopy conditions and losses of closed-canopy conditions. LSRs were more
      prone to wildfire than the region as a whole, and experienced slight declines in
      late seral conditions. Despite losses of late seral conditions, wildfires
      contributed to some conservation objectives by creating open habitats (e.g.,
      sparse early seral and woodland conditions) that otherwise generally decreased in
      unburned landscapes despite management efforts to increase landscape diversity.
      This study demonstrates the potential for wildfires to contribute to regional
      scale conservation objectives, but implications for management and biodiversity
      at landscape scales vary geographically among biophysical settings, and are
      contingent upon historical dynamics and individual species habitat preferences.

PMID- 29058764
TI  - Protective effects of PPAR-gamma against pregnancy-induced hypertension by
      differential ETR expression in rat models.
AB  - This study aims to investigate the effects of PPAR-gamma on rats with pregnancy
      induced hypertension (PIH) by regulating endothelin receptor (ETR). A total of 60
      pregnant Wistar rats were selected, and 50 rats were used to establish endotoxin
      induced PIH rat models. Rats were equally assigned into PIH-NS, PIH-5 mg/kg RM,
      PIH-10 mg/kg RM, PIH-100 mg/kg ETR, and PIH-200 mg/kg ETR groups, and the rest 10
      rats were assigned to a the control group. Reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) and Western blotting were used for
      determining mRNA and protein expressions of PPAR-gamma and ETA R, respectively.
      Protein expression of ET-1 was detected by immunohistochemistry. Results show
      that On the 22nd day of pregnancy, compared with the PIH-NS group, SBP decreased
      in other groups, and platelet concentration increased most significantly in the
      PIH-10 mg/kg RM and PIH-200 mg/kg ETR groups. Compared with the control, PIH-10
      mg/kg RM and PIH-200 mg/kg ETR groups, the increase in the expression of ET-1 and
      ETA R was most significant in the PIH-NS group. Compared with the control and PIH
      10 mg/kg RM groups, expression of PPAR-gamma was lower in the PIH-NS, PIH-5 mg/kg
      RM, PIH-100 mg/kg ETR, and PIH-200 mg/kg ETR groups. Compared with the PIH-NS,
      PIH-100 mg/kg ETR and PIH-200 mg/kg ETR groups, PPAR-gamma expression was
      significantly higher in the PIH-5 mg/kg RM group (all P < 0.05). Based on our
      findings, we conclude that PPAR-gamma activation inhibits ETR expression and
      reduces the effect of ET-1 on vascular contraction thereby delaying PIH
      progression.

PMID- 29058766
TI  - Fabrication and Optimization of Self-Microemulsions to Improve the Oral
      Bioavailability of Total Flavones of Hippophae rhamnoides L.
AB  - : The purpose of this work was to improve the oral bioavailability of a poorly
      soluble functional food ingredient, the total flavones of Hippophae rhamnoides L.
      (TFH). A self-microemulsion drug delivery system (SMEDDS) was developed to
      overcome the problems of poor absorption of TFH in vivo. The optimal SMEDDS
      significantly enhanced the solubility of TFH up to 530 times compared to that in
      water. The mean droplet size was 61.76 nm with uniform distribution. And the
      loaded system was stable at 25  degrees C for 3 mo with transparent appearance.
      The in vitro release of TFH from SMEDDS was faster and more complete than that
      from suspension. After oral administration of TFH-SMEDDS in rats, the relative
      bioavailability of TFH was dramatically improved for 3.09 times compared with the
      unencapsulated form. The investigation indicated the potential application of
      SMEDDS as a vehicle to improve the oral bioavailability of TFH. PRACTICAL
      APPLICATION: The lipid-based nanotechnology, namely self-microemulsion drug
      delivery system (SMEDDS) was used to improve the bioavailability and oral
      delivery of total flavones of Hippophae rhamnoides L. (TFH). The relevant
      bioavailability of TFH could be remarkably 3-fold improved by the optimized
      SMEDDS. The SMEDDS produced via a simple one-step process for poorly soluble TFH
      to achieve a significant improvement in the bioavailability, may endorse the
      promising utilization of TFH in functional foods as well as pharmaceutical fields
      with an enhanced absorption in vivo.

PMID- 29058767
TI  - Bioinspired Surfaces with Superwettability for Anti-Icing and Ice-Phobic
      Application: Concept, Mechanism, and Design.
AB  - Ice accumulation poses a series of severe issues in daily life. Inspired by the
      nature, superwettability surfaces have attracted great interests from fundamental
      research to anti-icing and ice-phobic applications. Here, recently published
      literature about the mechanism of ice prevention is reviewed, with a focus on the
      anti-icing and ice-phobic mechanisms, encompassing the behavior of condensate
      microdrops on the surface, wetting, ice nucleation, and freezing. Then, a
      detailed account of the innovative fabrication and fundamental research of anti
      icing materials with special wettability is summarized with a focus on recent
      progresses including low-surface energy coatings and liquid-infused layered
      coatings. Finally, special attention is paid to a discussion about advantages and
      disadvantages of the technologies, as well as factors that affect the anti-icing
      and ice-phobic efficiency. Outlooks and the challenges for future development of
      the anti-icing and ice-phobic technology are presented and discussed.

PMID- 29058769
TI  - Lewis Rat Model of Experimental Autoimmune Encephalomyelitis.
AB  - In this unit, we describe in detail the most common methods used to break
      immunological tolerance for central myelin antigens and induce experimental
      autoimmune encephalomyelitis (EAE) in Lewis rats as an animal model of multiple
      sclerosis. The resulting disease course ranges from an acute monophasic disease
      to a chronic relapsing or chronic progressive course, which strongly resembles
      the human disease. These models enable the study of cellular and humoral
      autoimmunity against major antigenic epitopes of the myelin basic protein, myelin
      oligodendrocyte glycoprotein, or proteolipid protein. We provide an overview of
      common immunization protocols for induction of active and passive EAE, assessment
      and analysis of clinical score, preparation and purification of myelin basic
      protein, and derivation of neuroantigen-specific rat T cell lines. Finally, we
      describe the major clinical characteristics of these models. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 29058770
TI  - Suppression of Red Blood Cell Autofluorescence for Immunocytochemistry on Fixed
      Embryonic Mouse Tissue.
AB  - Autofluorescence is a problem that interferes with immunofluorescent staining and
      complicates data analysis. Throughout the mouse embryo, red blood cells naturally
      fluoresce across multiple wavelengths, spanning the emission and excitation
      spectra of many commonly used fluorescent reporters, including antibodies, dyes,
      stains, probes, and transgenic proteins, making it difficult to distinguish assay
      fluorescence from endogenous fluorescence. Several tissue treatment methods have
      been developed to bypass this issue with varying degrees of success. Sudan Black
      B dye has been commonly used to quench autofluorescence, but can also introduce
      background fluorescence. Here we present a protocol for an alternative called
      TrueBlack Lipofuscin Autofluorescence Quencher. The protocol described in this
      unit demonstrates how TrueBlack efficiently quenches red blood cell
      autofluorescence across red and green wavelengths in fixed embryonic tissue
      without interfering with immunofluorescent signal intensity or introducing
      background staining. We also identify optimal incubation, concentration, and
      multiple usage conditions for routine immunofluorescence microscopy. (c) 2017 by
      John Wiley & Sons, Inc.

PMID- 29058768
TI  - The impact of endogenous content, replicates and pooling on genome capture from
      faecal samples.
AB  - Target-capture approach has improved over the past years, proving to be very
      efficient tool for selectively sequencing genetic regions of interest. These
      methods have also allowed the use of noninvasive samples such as faeces
      (characterized by their low quantity and quality of endogenous DNA) to be used in
      conservation genomic, evolution and population genetic studies. Here we aim to
      test different protocols and strategies for exome capture using the Roche SeqCap
      EZ Developer kit (57.5 Mb). First, we captured a complex pool of DNA libraries.
      Second, we assessed the influence of using more than one faecal sample, extract
      and/or library from the same individual, to evaluate its effect on the molecular
      complexity of the experiment. We validated our experiments with 18 chimpanzee
      faecal samples collected from two field sites as a part of the Pan African
      Programme: The Cultured Chimpanzee. Those two field sites are in Kibale National
      Park, Uganda (N = 9) and Loango National Park, Gabon (N = 9). We demonstrate that
      at least 16 libraries can be pooled, target enriched through hybridization, and
      sequenced allowing for the genotyping of 951,949 exome markers for population
      genetic analyses. Further, we observe that molecule richness, and thus, data
      acquisition, increase when using multiple libraries from the same extract or
      multiple extracts from the same sample. Finally, repeated captures significantly
      decrease the proportion of off-target reads from 34.15% after one capture round
      to 7.83% after two capture rounds, supporting our conclusion that two rounds of
      target enrichment are advisable when using complex faecal samples.

PMID- 29058771
TI  - Bioluminescence Resonance Energy Transfer Assay to Characterize Gi-Like G Protein
      Subtype-Dependent Functional Selectivity.
AB  - G protein-coupled receptors (GPCRs) comprise the single most targeted protein
      class in pharmacology. G protein signaling transduces extracellular stimuli such
      as neurotransmitters into cellular responses. Although preference for a specific
      GPCR among different G protein families (e.g., Gs-, Gi-, or Gq-like proteins) is
      often well studied, preference for a specific G protein subtype (e.g., Gi1, Gi2,
      Gi3, Go1, and Go2) has received little attention. Due to tissue expression
      differences and potentially exploitable functional differences, G protein subtype
      dependent functional selectivity is an attractive framework to expand GPCR drug
      development. Herein we present a bioluminescence resonance energy transfer (BRET)
      based method to characterize functional selectivity among Gi-like protein
      subtypes. (c) 2017 by John Wiley & Sons, Inc.

PMID- 29058772
TI  - Controlled Cortical Impact in the Rat.
AB  - Traumatic brain injury (TBI) is a major cause of death and disability world-wide.
      Following initial injury, TBI patients can face long-term disability in the form
      of cognitive, physical, and psychological deficits, depending on the severity and
      location of injury. This results in an economic burden in the United States
      estimated to be $60 billion due to health-care costs and loss of productivity.
      TBI is a significant area of active research interest for both military and
      civilian medicine. Numerous pre-clinical animal models of TBI are used to
      characterize the anatomical and physiological pathways involved and to evaluate
      therapeutic interventions. Due to its flexibility and scalability, controlled
      cortical impact (CCI) is one of the most commonly used preclinical TBI models.
      This unit provides a basic CCI protocol performed in the rat. (c) 2017 by John
      Wiley & Sons, Inc.

PMID- 29058773
TI  - The role of innate lymphoid cells in health and disease.
AB  - Innate lymphoid cells (ILCs) are kind of innate immune cells which can be divided
      into three main subsets according to their cytokine release profile,
      transcription factors, and surface markers. ILCs affect the initial stages of
      immunity in response to microbes and participate in immunity, inflammation, and
      tissue repair. ILCs modulate immunity through resistance to the pathogens and
      regulation of autoimmune inflammation and metabolic homeostasis. Therefore
      dysregulation of ILCs may lead to chronic pathologies such as allergies (i.e.,
      asthma), inflammation (i.e., inflammatory bowel disease), and autoimmunity (i.e.,
      psoriasis, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, and
      ankylosing spondylitis). Regarding the critical role of ILCs in the regulation of
      immune system, the elucidation of their function in different conditions makes an
      interesting target for improvement of novel therapeutic approach to modulate an
      immune response in different disease context.

PMID- 29058775
TI  - Comparative Molecular Dynamics Simulation of Aggregating and Non-Aggregating
      Inhibitor Solutions: Understanding the Molecular Basis of Promiscuity.
AB  - The presence of false positives in enzyme inhibition assays is a common problem
      in early drug discovery, especially for compounds that form colloid aggregates in
      solution. The molecular basis of these aggregates could not be thoroughly
      explored because of their transient stability. In this study we conducted
      comparative molecular dynamics (MD) simulations of miconazole, a strong
      aggregator, and fluconazole, a known non-aggregator. Interestingly, miconazole
      displays full aggregation within only 50 ns, whilst fluconazole shows no
      aggregation over the 500 ns simulation. The simulations indicate that the center
      of the aggregate is densely packed by the hydrophobic groups of miconazole,
      whereas polar and nonpolar groups comprise the surface to form a micelle-like
      colloid. The amphiphilic moment and planar nature of the miconazole structure
      appear to promote its aggregating behavior. The simulations also predict rapid
      aggregate formation for a second known promiscuous inhibitor, nicardipine. Thus,
      MD appears to be a useful tool to characterize aggregate-prone inhibitors at
      molecular-level detail and has the potential to provide useful information for
      drug discovery and formulation design.

PMID- 29058774
TI  - Mesoderm-specific transcript localization in the ER and ER-lipid droplet
      interface supports a role in adipocyte hypertrophy.
AB  - Highly variable expression of mesoderm-specific transcript (Mest) in adipose
      tissue among genetically homogeneous mice fed an obesogenic diet, and its
      positive association with fat mass expansion, suggests that Mest is an epigenetic
      determinant for the development of obesity. Although the mechanisms by which MEST
      augments fat accumulation in adipocytes have not been elucidated, it has sequence
      homology and catalytic peptide motifs which suggests that it functions as an
      epoxide hydrolase or as a glycerol- or acylglycerol-3-phosphate acyltransferase.
      To better understand MEST function, detailed studies were performed to precisely
      define the intracellular organelle localization of MEST using immunofluorescence
      confocal microscopy. Lentiviral-mediated expression of a C-terminus Myc-DDK
      tagged MEST fusion protein expressed in 3T3-L1 preadipocytes/adipocytes, and ear
      derived mesenchymal stem cells (EMSC) from mice was observed in the endoplasmic
      reticulum (ER) membranes and is consistent with previous studies showing
      endogenous MEST in the membrane fraction of adipose tissue. MEST was not
      associated with the Golgi apparatus or mitochondria; however, frequent contacts
      were observed between MEST-positive ER and mitochondria. MEST-positive domains
      were also shown on the plasma membrane (PM) of non-permeabilized cells but they
      did not co-localize with ER-PM bridges. Post-adipogenic differentiated 3T3-L1
      adipocytes and EMSC showed significant co-localization of MEST with the lipid
      droplet surface marker perilipin at contact points between the ER and lipid
      droplet. Identification of MEST as an ER-specific protein that co-localizes with
      lipid droplets in cells undergoing adipogenic differentiation supports a function
      for MEST in the facilitation of lipid accumulation and storage in adipocytes.

PMID- 29058777
TI  - MicroRNA-103 confers the resistance to long-treatment of adriamycin to human
      leukemia cells by regulation of COP1.
AB  - Adriamycin (ADR) is an anti-cancer drug which offers improvement in survival for
      acute myeloid leukemia (AML) patients. However, the drug resistance is almost
      inevitable. Increasing evidences suggested that microRNAs (miRNAs) were
      associated with cancer chemo-resistance. Here, we aimed to explore the possible
      mechanism of miR-103 affected resistance to ADR in AML cells. Different
      concentrations of ADR were used to induce K562 and KASUMI-1 cells, and miR-103
      mimic, inhibitor were transfected into K562 and KASUMI-1 cells. Cell viability
      and proliferation were determined by trypan blue staining and MTT assays for
      evaluating K562 and KASUMI-1 cells drug resistance. The relationship of miR-103
      and COP1, Trib1, and C/EBPalpha were analyzed by qRT-PCR and Western blot. Cell
      proliferation, viability were detected again. Besides, the expressions of main
      factors of cell cycle and PI3K/AKT signal pathway were analyzed by Western blot.
      Results showed that ADR inhibited cell viability and proliferation in K562 and
      KASUMI-1 cells. However, K562 and KASUMI-1 cells appeared drug resistance for 50
      passages at 0.8 uM of ADR. In addition, miR-103 expression was up-regulated in
      ADR-resistant K562 cells (K562/ADR) and overexpression of miR-103 increased K562
      cells drug resistance via promoting cell viability and cell cycle-related factors
      expressions. COP1 was positively regulated by miR-103, suppression of miR-103
      recovered K562/ADR cells drug resistance by regulation of COP1, Trib1, and
      C/EBPalpha. Besides, miR-103 blocked PI3K/AKT signal pathway by regulation of
      COP1. These data indicated that miR-103 was up-regulated in drug resistant cells
      and it may regulate ADR-resistance by regulation of COP1 in AML cells.

PMID- 29058776
TI  - Osteophytes and fracture calluses share developmental milestones and are
      diminished by unloading.
AB  - Osteophytes are a typical radiographic finding during osteoarthritis (OA), but
      the mechanisms leading to their formation are not well known. Comparatively,
      fracture calluses have been studied extensively; therefore, drawing comparisons
      between osteophytes and fracture calluses may lead to a deeper understanding of
      osteophyte formation. In this study, we compared the time courses of osteophyte
      and fracture callus formation, and investigated mechanisms contributing to
      development of these structure. Additionally, we investigated the effect of
      mechanical unloading on the formation of both fracture calluses and osteophytes.
      Mice underwent either transverse femoral fracture or non-invasive anterior
      cruciate ligament rupture. Fracture callus and osteophyte size and ossification
      were evaluated after 3, 5, 7, 14, 21, or 28 days. Additional mice were subjected
      to hindlimb unloading after injury for 3, 7, or 14 days. Protease activity and
      gene expression profiles after injury were evaluated after 3 or 7 days of normal
      ambulation or hindlimb unloading using in vivo fluorescence reflectance imaging
      (FRI) and quantitative PCR. We found that fracture callus and osteophyte growth
      achieved similar developmental milestones, but fracture calluses formed and
      ossified at earlier time points. Hindlimb unloading ultimately led to a threefold
      decrease in chondro/osteophyte area, and a twofold decrease in fracture callus
      area. Unloading was also associated with decreased inflammation and protease
      activity in injured limbs detected with FRI, particularly following ACL rupture.
      qPCR analysis revealed disparate cellular responses in fractured femurs and
      injured joints, suggesting that fracture calluses and osteophytes may form via
      different inflammatory, anabolic, and catabolic pathways. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:699-710,
      2018.

PMID- 29058778
TI  - Conversion of Triple Bonds into Single Bonds in a Domino Carbopalladation with
      Norbornene.
AB  - A domino carbopalladation reaction of haloalkynes is presented. Remarkably, the
      four-time carbopalladation process converts the carbon-carbon triple bonds of
      haloalkynes stepwise into carbon-carbon double bonds, and finally to carbon
      carbon single bonds. Features of this reaction are that the carbon-carbon double
      bonds of stable vinyl palladium intermediates are transformed into carbon-carbon
      single bonds with the generation of unstable alkyl palladium intermediates. The
      subsequently formed pi-allylpalladium species are independently trapped by N
      tosylhydrazones, boronic acids, and B2 pin2 in a highly diastereoselective
      manner, delivering the corresponding polycyclic and twisted products with a
      bicyclo[3.2.1]oct-2-en-3-yl)tricyclo[3.2.1.02,4 ]octane core skeleton in moderate
      to good yields via C-C and C-B bond formations. Significantly, the dual roles of
      norbornenes, ring construction and ring expansion, and the identification of
      electron-rich tri(2-furyl)phosphine as the ligand are found to be critical for
      the success of these transformations.

PMID- 29058779
TI  - The Combination of icariin and constrained dynamic loading stimulation attenuates
      bone loss in ovariectomy-induced osteoporotic mice.
AB  - Osteoporosis is a disease characterized by low bone mass and progressive
      destruction of bone microstructure, resulting in increasing the risk of fracture.
      Icariin (ICA) as a phytoestrogen shows osteogenic effects, and the mechanical
      stimulation has been demonstrated the improving effect on osteoporosis. The
      objective of this study was to investigate the effect of ICA in combination with
      constrained dynamic loading (CDL) stimulation on osteoporosis in ovariectomized
      (OVX) mice. The serum hormone levels, bone turnover markers, trabecular
      architecture, ulnar biomechanical properties, and the expression of osteoblast
      related gene (alkaline phosphatase, ALP; osteocalcin, OCN; bone morphogenetic
      protein-2, BMP-2; Collagen I (alpha1), COL1; osteoprotegerin, OPG) and osteoclast
      related genes (receptor activators of NF-kappaB ligand, RANKL; tartrate-resistant
      acid phosphatase, TRAP) were analyzed. The results showed that ICA + CDL
      treatment could increase the osteocalcin (20.85%), estradiol levels (20.61%) and
      decrease the TRAP activity (26.27%) significantly than CDL treatment. The
      combined treatment attenuated bone loss and biomechanical decrease more than
      single use of CDL treatment. ICA + CDL treatment significantly up-regulated the
      level of osteoblast-related gene expression and down-regulated the osteoclast
      related genes expression; moreover, the combined treatment increased the ratio of
      OPG/RANKL significantly compared to ICA (72.83%) or CDL (65.63%) treatment alone.
      The present study demonstrates that icariin in combination with constrained
      dynamic loading treatment may have a therapeutic advantage over constrained
      dynamic loading treatment alone for the treatment of osteoporosis, which would
      provide new evidence for the clinical treatment of osteoporosis. (c) 2017
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:1415-1424, 2018.

PMID- 29058781
TI  - Access to alpha-Amino Acid Esters through Palladium-Catalyzed Oxidative Amination
      of Vinyl Ethers with Hydrogen Peroxide as the Oxidant and Oxygen Source.
AB  - A novel and convenient palladium catalytic system for the synthesis of alpha
      amino acid esters from simple starting materials is reported. Hydrogen peroxide
      not only acts as the green oxidant, but also as the oxygen source. This strategy
      for the conversion of amines and vinyl ethers into highly functionalized and
      structurally diverse alpha-amino acid esters is characterized by the simplicity
      of the experimental procedure, mild reaction conditions, high atom economy,
      scalability, and practicability.

PMID- 29058780
TI  - Effective and efficient lymphaticovenular anastomosis using preoperative
      ultrasound detection technique of lymphatic vessels in lower extremity
      lymphedema.
AB  - BACKGROUND: Identification of functional lymphatic vessels and localization of
      lymphatic vessels are important for lymphaticovenular anastomosis (LVA).
      Indocyanine green (ICG) lymphography is useful for localization of superficial
      lymphatic vessels where dermal backflow is not observed, but not for lymphatic
      vessels in deep layer or where dermal backflow is observed. Ultrasound has been
      applied in LVA and is considered useful for localization of lymphatic vessels
      with ICG lymphography cannot be visualized. METHODS: Fifty-five secondary lower
      extremity lymphedema (LEL) patients who underwent LVA were classified into two
      groups, ultrasound-detection-of-lymphatic group (US group, n = 29) and non
      ultrasound-detection-of-lymphatic group (non-US group, n = 26), and assessed.
      Sensitivity and specificity to detect lymphatic vessel were evaluated in US
      group. Intraoperative findings, required time for dissecting lymphatic vessels
      and veins, length of skin incision, and postoperative lymphedematous volume
      reduction were compared between the groups. RESULTS: Lymphatic vessels were
      detected in all incisions in both groups. LVA resulted in 232 anastomoses in US
      group and 210 anastomoses in non-US group. Sensitivity and specificity of
      ultrasound for detection of lymphatic vessels were 88.2% and 92.7%, respectively.
      Diameter of lymphatic vessels found in US group was significantly larger than
      that in non-US group (0.66 +/- 0.18 vs 0.45 +/- 0.20 mm; P = 0.042). Time
      required for dissecting lymphatic vessels and veins in US group was shorter than
      that in non-US group (9.2 +/- 1.7 vs 14.7 +/- 2.4 min; P = 0.026). LEL index
      reduction was significantly greater in US group than that in non-US group (26.7
      +/- 13.6 vs 7.8 +/- 11.3; P = 0.031). CONCLUSIONS: Ultrasound-guided detection of
      lymphatic vessels for lymphedema was performed with high precision, and allows
      easier and more effective LVA surgery.

PMID- 29058782
TI  - The Relation Between Walking and Language in Infant Siblings of Children With
      Autism Spectrum Disorder.
AB  - In typical development, walk onset is accompanied by increased language growth
      (e.g., Walle & Campos, 2014). The present study explored whether this relation
      may be disrupted in the infant siblings of children with autism spectrum disorder
      (ASD; heightened risk of receiving an ASD diagnosis; HR), a population exhibiting
      substantial variability in motor and language development (e.g., Gamliel,
      Yirmiya, & Sigman, 2007; Landa & Garrett-Mayer, 2006). Receptive and expressive
      language were examined across the transition to walking in three groups of HR
      infants (no diagnosis, language delay, and ASD; N = 91, 8-18 months) and in
      infants with no family history of ASD (N = 25; 9-15 months). Only infants with an
      eventual ASD diagnosis did not show increased language growth following walk
      onset.

PMID- 29058783
TI  - From mutational inactivation to aberrant gain-of-function: Unraveling the
      structural basis of mutant p53 oncogenic transition.
AB  - Various evidence has revealed that mutations in p53 exert activities that go
      beyond simply inactivation of wildtype functions but rather elicits downstream
      interactions that promote malignancy described as mutant p53 gain-of-function
      (GOF). Here we report the first account of the dynamics of mutation-induced
      structural transition of native p53 to an aberrant gain-of-function state,
      studying the wildtype (WT) and high incidence contact (R273C) and structural
      (R175H) mutant p53 (mutp53) through molecular dynamics simulation. Result
      analysis revealed that both mutants exhibited structural distortion and reduced
      flexibility, indicative of rigidity and kinetic stability. In addition, surface
      analysis revealed an increase in the accessible surface area in the p53 mutants.
      This suggests that the GOF transition involves protein unfolding and exposure of
      buried hydrophobic surface essential for interaction with HSF-1 oncogenic partner
      and wildtype p63, and p73 homologs. Further validation revealed binding cavities,
      similar in the mutants but dissimilar to the WT. Taken together, this study
      complements experimental findings and reveals the interplay between mutation
      induced structural distortion, loss of flexibility, rigidity, enhanced stability,
      protein unfolding and ultimately, exposure of binding surfaces as conformational
      attributes that characterize mutP53 structure-GOF activities. This insight is,
      therefore, of great importance as it opens up a novel therapeutic approach toward
      the structure based targeting of mutP53 oncogenic involvement beyond wildtype
      inactivation. Furthermore, "exposed" binding site information obtained from this
      study can be explored for structure-based design of substances best described as
      "destabilizers" to disrupt the GOF interaction of mutp53.

PMID- 29058784
TI  - MicroRNA-21 antisense oligonucleotide improves the sensitivity of A375 human
      melanoma cell to Cisplatin: An in vitro study.
AB  - This study explored Cisplatin resistance effect of microRNA-21 (miR-21) antisense
      oligonucleotide (AS-ODN) in human melanoma A375 cell. AS-ODN was transfected in
      melanoma A375 cells and Cisplatin-resistant cell line A375/CDDP, and divided into
      the AS-ODN, nonsense oligonucleotide (NS-ODN) and normal groups. Cell
      ultrastructure changes were observed through transmission electron microscope.
      MiR-21 AS-ODN could be tested cell growth effect in different time periods by
      trypan blue exclusion. MiR-21 mRNA expression change was detected by quantitative
      fluorescence PCR. Cell apoptosis, cycle distribution and miR-21 AS-ODN effect on
      proliferation and Cisplatin sensitivity were tested by flow cytometry, MTT assay,
      TUNEL, and Clonogenic assay. Cell apoptosis was observed after transfection 24 h
      with the AS-ODN group, while the NS-ODN and normal group cells had no apoptotic
      symptoms; Compared with the normal group, the AS-ODN group began to show obvious
      cell growth inhibition effect after transfection 24 h lasting 72 h (all P <
      0.05), but the NS-ODN group had no significant difference (P > 0.05). miR-21 mRNA
      expression in the AS-ODN group was obviously decreased with rising apoptosis rate
      (all P < 0.05) and there was no significant difference in the NS-ODN group (P >
      0.05). MiR-21 AS-ODN could remarkably increase A375 cell and A375/CDDP cell
      sensitivity to Cisplatin (P < 0.05), while A375 cell sensitivity to Cisplatin
      between the NS-ODN group and the normal group had no difference. MiR-21 AS-ODN
      decreased IC50 and increased Cisplatin sensitivity for A375 cells and A375/CDDP
      cells, which would be a new target of melanoma treatment.

PMID- 29058785
TI  - Piezo-Phototronic Matrix via a Nanowire Array.
AB  - Piezoelectric semiconductors, such as ZnO and GaN, demonstrate multiproperty
      coupling effects toward various aspects of mechanical, electrical, and optical
      excitation. In particular, the three-way coupling among semiconducting,
      photoexcitation, and piezoelectric characteristics in wurtzite-structured
      semiconductors is established as a new field, which was first coined as piezo
      phototronics by Wang in 2010. The piezo-phototronic effect can controllably
      modulate the charge-carrier generation, separation, transport, and/or
      recombination in optical-electronic processes by modifying the band structure at
      the metal-semiconductor or semiconductor-semiconductor heterojunction/interface.
      Here, the progress made in using the piezo-phototronic effect for enhancing
      photodetectors, pressure sensors, light-emitting diodes, and solar cells is
      reviewed. In comparison with previous works on a single piezoelectric
      semiconducting nanowire, piezo-phototronic nanodevices built using nanowire
      arrays provide a promising platform for fabricating integrated optoelectronics
      with the realization of high-spatial-resolution imaging and fast responsivity.

PMID- 29058786
TI  - Jasmonate signaling makes flowers attractive to pollinators and repellant to
      florivores in nature.
AB  - Flowers are required for the Darwinian fitness of flowering plants, but flowers'
      advertisements for pollination services can attract florivores. Previous
      glasshouse work with Nicotiana attenuata revealed the role of jasmonate (JA)
      signaling in flower development, advertisement and defense. However, whether JA
      signaling mediates flowers' filtering of floral visitors in nature remained
      unknown. This field study revealed that silencing JA signaling resulted in
      flowers that produce less nectar and benzyl acetone, two pollinator-attractive
      traits. Meanwhile, flowers of defenseless plants were highly attacked by a suite
      of native herbivores, and damage to buds in native plants correlated negatively
      with their JA-Ile levels.

PMID- 29058787
TI  - Drug repurposing: An approach to tackle drug resistance in S. typhimurium.
AB  - Drug resistant S. typhimurium pose important public health problem. The
      development of effective drugs with novel mechanism(s) of action is needed to
      overcome issues pertaining to drug resistance. Drug repurposing based on
      computational analyses is considered a viable alternative strategy to circumvent
      this issue. In this context, 1309 FDA-approved drugs molecules from Mantra 2.0
      database were analyzed for this study, against S. typhimurium. Sixteen compounds
      having similar profiles of gene expression as quinolones were identified from the
      database, Mantra 2.0. Further, the pharmacophore characteristics of each
      resultant molecule were identified and compared with the features of nalidixic
      acid, using the PharamGist program. Subsequently, the activities of these
      compounds against S. typhimurium DNA gyrase were identified, using molecular
      docking study. Side effects analysis was also performed for the identified
      compounds. Molecular dynamics simulation was carried out for the compound to
      validate its binding efficiency. Further, characterization of screened compound
      revealed IC50 values in micromolar concentration range, of which flufenamic acid
      showed comparable in vitro activity alongside ciprofloxacin and nalidixic acid.
      Thus represent interesting starting points for further optimization against S.
      typhimurium infections. It may be noted that the results we have obtained are the
      first experimental evidence of flufenamic acid activity against S. typhimurium.

PMID- 29058788
TI  - Significant skin-tightening by closure of fractional ablative laser holes.
AB  - BACKGROUND AND OBJECTIVE: Ablative fractional laser treatment uses thousands of
      very small laser beam wounds to damage a fraction of the skin, which stimulates
      tissue remodeling. Each open micro-wound heals without scarring, but the amount
      of skin tightening achieved is limited. This animal study was performed to test
      the hypothesis that immediate temporary closure of fractional laser wounds could
      increase skin tightening after fractional ablative laser treatment. MATERIALS AND
      METHODS: Four adult swine were used for the study; 98 square test sites (3 * 3
      cm) were tattooed on the abdomen and flanks of each pig. An ablative fractional
      Erbium:YAG laser (Sciton Profile, Sciton Inc, Palo Alto, CA) was used to treat
      the test areas. A laser micro-spot fluence of 375 J/cm2 was delivered in 150-250
      microseconds pulses, resulting in an array of ablation channels extending 1.5 mm
      deep into the skin, with a spot size of 250 um, with 10% treatment density.
      Immediately following laser exposure the resulting holes were closed using a
      stretched elastic adhesive dressing, which, when applied, recoiled and compressed
      the diameter of the ablation holes. The compressive dressings were removed after
      7 days. This procedure was compared to removing the same amount of skin (10%)
      mechanically by specially designed 19 gauge coring needles, as well as to the
      same laser and coring methods without compression closure. Area and shape of test
      sites were measured by digital photography before and 28 days after treatment.
      Data analysis included compensation for animal growth, as measured by increase in
      the area of the untreated control sites. RESULTS: All treated and control sites
      healed within a week, without scarring evident at 28 days. Laser treatment
      combined with compressive wound closure caused significant shrinkage at 28 days
      compared with untreated control sites. The treated skin area was reduced by 11.5%
      (P = 0.0001). Needle coring with wound closure produced similar, significant
      shrinkage (8%, P < 0.0021), whereas laser and needle coring treatment without
      closure did not result in significant area reduction (P = 0.1289) compared with
      untreated control sites. CONCLUSION: Significant skin tightening can be achieved
      by immediate temporary non-invasive wound closure after short pulse Er:YAG
      fractional ablative laser treatment, as well as after mechanically removing skin
      with a coring needle. This approach may improve skin tightening after ablative
      laser treatments. Further clinical studies are necessary to confirm successful
      application in humans. Lasers Surg. Med. 50:64-69, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29058790
TI  - Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical
      cancer.
AB  - Aberrant activation of the HGF/c-Met signalling pathway is reported to be
      associated with cell proliferation, progression, and metastasis features of
      several tumor types, including cervical cancer, suggesting that it may be of
      potential value as a novel therapeutic target. Furthermore, HPV-positive patients
      had a higher serum level of HGF or c-Met protein, compared with HPV-negative
      patients. c-Met or HGF overexpression in lesions of cervical cancer is reported
      to be related to a poorer prognosis, and hence this may be of value as a
      prognostic and predictive biomarker. Several approaches have been developed for
      targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK
      inhibitor). This has been approved by FDA for the treatment of lung-cancer.
      Further investigations are required to evaluate and optimize the use of c-Met
      inhibitors in cervical cancer or parallel targeting signalling pathway
      associated/activated via MET/HGF pathway. The main aim of current review was to
      give an overview of the potential of the c-Met/HGF pathway as a prognostic, or
      predictive biomarker in cervical cancer.

PMID- 29058789
TI  - Sleep, biological stress, and health among toddlers living in socioeconomically
      disadvantaged homes: A research protocol.
AB  - Healthy sleep is important to behavioral, neurobiological, and physiologic
      health. In older children and adults, stress biomarkers, such as cortisol and C
      reactive protein, increase when they do not practice healthy sleep habits.
      However, little is known about the relationships among sleep health, stress, and
      health outcomes among very young children living with socioeconomic adversity, a
      group that is particularly at risk for poor future health. The NIH-funded study
      described in this protocol addresses this scientific gap to improve understanding
      of these relationships during a critical developmental period in children's lives
      toddlerhood. We will use a longitudinal design with repeated measures to
      prospectively examine the relationships among sleep health, stress, and toddlers'
      health from age 12 to 24 months, to address the following aims: i) examine
      changes in subjective and objective sleep health measures; ii) examine changes in
      stress biomarkers; iii) examine the cross-sectional and longitudinal
      relationships between sleep health measures and stress response; and iv) examine
      the cross-sectional and longitudinal relationships between sleep health measures,
      stress biomarkers, and toddlers' behavioral health. The sample will include 113
      toddlers and their caregivers. We are collecting subjective and objective data on
      sleep health, multi-systemic biomarkers of stress, and toddlers' behavioral
      health. Generalized linear models will be used in the data analyses. Results from
      this study will be used to support development and testing of interventions, such
      as those that may improve sleep, among young children at risk for toxic stress.

PMID- 29058791
TI  - In vitro and in vivo effect of PD-1/PD-L1 blockade on microglia/macrophage
      activation and T cell subset balance in cryptococcal meningitis.
AB  - This study aimed to investigate the PD-1/ PD-L1 signaling pathway and its effects
      the activation of microglia/macrophage and balancing T cell subsets in
      cryptococcal meningitis (CM). A total of 126 CM patients and 126 healthy
      individuals were recruited for the study. The CM patients were treated with
      amphotericin B (AmB). Seventy five C57BL/6 mice were grouped into the normal
      control, CM model, CM + AmB, sham, and CM + PD-1 antibodies (Ab) groups. CD4+ and
      CD8+ T cells as well as microglia/macrophages were analyzed by means of flow
      cytometry. Ionized calcium-binding adaptor molecule 1 (Ibal) expression was
      detected using western blotting and immunohistochemistry techniques. And the
      expression of Rab5 and Rab11 were detected using an immunofluorescence assay.
      Both PD-1 and PD-L1 mRNA and protein expression among the mice in the study were
      evaluated by qRT-PCR and western blotting methods. Compared to the CM model
      group, the CM + AmB and CM + PD-1 Ab groups exhibited increased levels of Th1
      cytokines and chemokines expression, and reduced levels of Th2 cytokines
      expressions. Elevated cell purity and viability of CD4+ T cell were recorded as
      well as increases in microglia, however, there were reductions in the number of
      CD8+ T cells. Depleted expressions of Ibal, Rab5, and Rab11 as well as reduced
      mRNA expressions of PD-1 and PD-L1 in CD4+ , microglia, and macrophage cells. The
      findings suggested that suppression of the PD-1/PD-L1 signaling pathway restricts
      the proliferation of CM by down-regulating the expressions of Th2 cells and
      suppressing microglia and macrophage activation.

PMID- 29058792
TI  - Association between oxidized low-density lipoprotein and cognitive impairment in
      patients with ischemic stroke.
AB  - BACKGROUND AND PURPOSE: The association between oxidized low-density lipoprotein
      (oxLDL) and cognitive impairment is unclear. This study aimed to investigate the
      potential association between oxLDL and cognitive impairment among patients with
      acute ischemic stroke. METHODS: We measured the levels of oxLDL and recorded the
      Mini-Mental State Examination (MMSE) score in patients with acute ischemic stroke
      who were recruited from the Study of Oxidative Stress in Patients with Acute
      Ischemic Stroke. Cognitive impairment was defined as an MMSE score of <24. The
      association between oxLDL and cognitive impairment was assessed by multivariate
      logistic or linear regression analysis. Other clinical variables of interest were
      also studied. RESULTS: A total of 3726 patients [1287 (34.54%) female] were
      included in this study, with a mean age of 63.62 +/- 11.96 years. After adjusting
      for potential confounders in our logistic regression model, each SD increase in
      oxLDL was associated with a 26% increase in the prevalence of cognitive
      impairment (odds radio, 1.26; 95% confidence interval, 1.13-1.39; P < 0.0001).
      Similarly, higher oxLDL was associated with lower MMSE scores, with a 0.56-point
      decrease in MMSE score for every SD increase in oxLDL in a linear regression
      analysis (beta = -0.56; 95% confidence interval, -0.81 to -0.32; P < 0.0001).
      There were no significant interactions between oxLDL and age, sex or education
      levels for cognitive impairment (all interactions, P > 0.05). CONCLUSIONS:
      Elevated levels of oxLDL were associated with a higher prevalence of cognitive
      impairment in patients with ischemic stroke.

PMID- 29058793
TI  - Photovoltaic-Pyroelectric Coupled Effect Induced Electricity for Self-Powered
      Photodetector System.
AB  - Ferroelectric materials have demonstrated novel photovoltaic effect to scavenge
      solar energy. However, most of the ferroelectric materials with wide bandgaps
      (2.7-4 eV) suffer from low power conversion efficiency of less than 0.5% due to
      absorbing only 8-20% of solar spectrum. Instead of harvesting solar energy, these
      ferroelectric materials can be well suited for photodetector applications,
      especially for sensing near-UV irradiations. Here, a ferroelectric BaTiO3 film
      based photodetector is demonstrated that can be operated without using any
      external power source and a fast sensing of 405 nm light illumination is enabled.
      As compared with photovoltaic effect, both the responsivity and the specific
      detectivity of the photodetector can be dramatically enhanced by larger than 260%
      due to the light-induced photovoltaic-pyroelectric coupled effect. A self-powered
      photodetector array system can be utilized to achieve spatially resolved light
      intensity detection by recording the output voltage signals as a mapping figure.

PMID- 29058794
TI  - Erythematous and hypopigmented streaks of thinned dermis along Blaschko's lines.

PMID- 29058795
TI  - Fatty acid synthase knockout impairs early embryonic development via induction of
      endoplasmic reticulum stress in pigs.
AB  - Fatty acid synthase (FAS) is an important enzyme involved in the de novo
      synthesis of long-chain fatty acids. During development, the function of FAS in
      growth is greater than that in energy storage pathways; therefore, we
      hypothesized that knockout of FAS would affect early embryonic development owing
      to the induction of endoplasmic reticulum (ER) stress. In the present study, the
      function of FAS was studied using the CRISPR (clustered regularly interspaced
      short palindromic repeats)/ CRISPR-associated protein 9 (Cas9) system. Cas9 and
      single-guide RNA (sgRNA) were injected into parthenotes to decrease the number of
      FAS-positive embryos. The efficiency of knockout was assayed by DNA sequencing.
      We found that FAS knockout caused excessive production of reactive oxygen species
      (ROS). Excess ROS induced ER stress, resulting in activation of the adaptive
      unfolded protein response (UPR). FAS knockout caused splicing of the X-box
      binding protein 1 gene (XBP1) and expression of spliced XBP1 mRNA. In addition,
      FAS knockout caused phosphorylation of PKR-like ER kinase (PERK), and an increase
      in the mRNA expression of the ER stress-regulated genes, activating transcription
      factor 4 (ATF4), and C/EBP homologous protein (CHOP). Finally, Ca2+ was released
      from the ER and taken up by the mitochondria. As the ER stress became
      intolerable, apoptosis was initiated. These results demonstrate that FAS knockout
      induced ROS generation, which mediated the activation of UPR via the ER stress,
      ultimately leading to apoptosis induction.

PMID- 29058796
TI  - Evolutionary Metal Oxide Clusters for Novel Applications: Toward High-Density
      Data Storage in Nonvolatile Memories.
AB  - Because of current fabrication limitations, miniaturizing nonvolatile memory
      devices for managing the explosive increase in big data is challenging. Molecular
      memories constitute a promising candidate for next-generation memories because
      their properties can be readily modulated through chemical synthesis. Moreover,
      these memories can be fabricated through mild solution processing, which can be
      easily scaled up. Among the various materials, polyoxometalate (POM) molecules
      have attracted considerable attention for use as novel data-storage nodes for
      nonvolatile memories. Here, an overview of recent advances in the development of
      POMs for nonvolatile memories is presented. The general background knowledge of
      the structure and property diversity of POMs is also summarized. Finally, the
      challenges and perspectives in the application of POMs in memories are discussed.

PMID- 29058798
TI  - Antiadhesion Organogel Materials: From Liquid to Solid.
AB  - Various organogel materials with either a liquid or solid surface layer have
      recently been designed and prepared. These surface materials can substantially
      reduce the adhesion of foreign deposits such as water, blood, paint, ice, and so
      on; therefore, they exhibit great potential for the easy removal of foreign
      deposits. Here, a brief discussion about the mechanism of organogel materials in
      reducing adhesion is given; then, examples of liquid organogels for fighting
      against varieties of complex fluidic deposits are presented, and efforts in
      preventing the depletion of liquid are discussed. Finally, applications of
      antiadhesion organogels with multifunctionality, and the strategy of replacing
      liquids with solids are presented.

PMID- 29058797
TI  - The fabrication of 3D surface scaffold of collagen/poly (L-lactide-co
      caprolactone) with dynamic liquid system and its application in urinary
      incontinence treatment as a tissue engineered sub-urethral sling: In vitro and in
      vivo study.
AB  - AIMS: To fabricate a novel nanoyarn biomaterial via a dynamic liquid
      electrospinning system, and to simultaneously evaluate whether nanoyarn is
      capable of being applied as a urinary sling for future clinical transfer.
      METHODS: Nanoyarn was cultured with adipose-derived stem cells (ADSCs). Cell
      morphology and function were observed on nanoyarn. Female rats that underwent
      vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the
      urinary incontinence model. After 2 weeks, the cells-sling was fixed to the
      suburethra. A commercial sling that tension-free vaginal tape-obturator (TVT-O)
      was used as a control. The urodynamic test for leak point pressure (LPP) and
      histological tests were used to evaluate the sling's performance in vivo.
      RESULTS: The nanoyarn possessed beneficial properties and the actin filament from
      ADSCs, which is very similar to muscle. Rats that underwent VD and BOR maintained
      a low LPP, whereas the LPP in rats with VD alone recovered to normal levels
      within 2 weeks. LPP in the nanoyarn group gradually decreased on the three
      urodynamic tests post-suburethral surgery, however, the cell-laden nanoyarn
      maintained LPP at normal levels for 8 weeks; the TVT-O group showed a significant
      increase in LPP at 8 weeks. Cell-laden nanoyarn was infiltrated with more cells,
      collagen, and vessels than the controls. CONCLUSIONS: The nanoyarn showed
      sufficient efficacy to maintain LPP in urinary incontinence rat model. In
      addition, it improved cell infiltration, collagen and muscle development compared
      to TVT-O. Thus, the combination of ADSCs and a nanoyarn scaffold could be a
      promising tissue-engineered sling for the treatment of urinary incontinence.

PMID- 29058799
TI  - A Supramolecular Nanocomposite as a Near-Infrared-Transmitting Optical Filter for
      Security and Forensic Applications.
AB  - Visibly opaque but near-infrared (NIR)-transparent materials are an essential
      component for night-vision photography, security imaging, and forensic
      applications. Herein, the development of a novel supramolecular black dye from a
      diketopyrrolopyrrole (DPP)-based low-molecular-weight organogelator is described.
      In the solution state, the monomer of DPP-Amide exhibits a deep green color with
      a broad absorption in the visible region due to firm intramolecular charge
      transfer from the donor to the acceptor unit. Interestingly, due to the
      synergistic effect of H-bonding and pi-stacking, DPP-Amide can form a black
      organogel in toluene with complete spectral coverage from 300 to 800 nm, and
      transmits beyond 850 nm. In the gel state, complete visible-spectrum coverage is
      achieved due to the simultaneous formation of both H- and J-type aggregates,
      which is confirmed via absorption studies. To create a free-standing NIR
      transmitting elastomeric black filter, nanoscopic molecular aggregates of DPP
      Amide (0.15 wt%) are embedded into a poly(dimethylsiloxane) matrix. This
      nanocomposite possesses high NIR transparency with good thermal and
      photostability for practical applications. Finally, the use of the developed
      material for NIR photography, security, and forensic-related applications is
      demonstrated.

PMID- 29058800
TI  - On-Skin Triboelectric Nanogenerator and Self-Powered Sensor with Ultrathin
      Thickness and High Stretchability.
AB  - Researchers have devoted a lot of efforts on pursuing light weight and high
      flexibility for the wearable electronics, which also requires the related energy
      harvesting devices to have ultrathin thickness and high stretchability. Hence, an
      elastic triboelectric nanogenerator (TENG) is proposed that can serve as the
      second skin on human body. The total thickness of this TENG is about 102 um and
      the device can work durably under a strain of 100%. The carbon grease is painted
      on the surface of elastomer film to work as stretchable electrode and thus the
      fine geometry control of the electrode can be achieved. This elastic TENG can
      even work on the human fingers without disturbing body movement. The open-circuit
      voltage and short-circuit current from the device with a contact area of 9 cm2
      can reach 115 V and 3 uA, respectively. Two kinds of self-powered sensor systems
      with optimized identification strategies are also designed to demonstrate the
      application possibility of this elastic TENG. The superior characteristics of
      ultrathin thickness, high stretchability, and fine geometry control of this TENG
      can promote many potential applications in the field of wearable self-powered
      sensory system, electronics skin, artificial muscles, and soft robotics.

PMID- 29058801
TI  - Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects.
AB  - Venetoclax has been approved in the United States, Europe, Canada, and Australia
      for appropriate patients with difficult-to-treat chronic lymphocytic leukemia
      (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics
      of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a
      phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve
      healthy first-generation Han Chinese subjects received a single 100-mg dose of
      venetoclax following a low-fat breakfast. Pharmacokinetic parameters were
      estimated using noncompartmental methods. After a single dose of venetoclax in
      healthy Chinese subjects, the median time to peak concentration was 6 hours
      (range, 4 to 6 hours), and the mean +/- SD Cmax , AUCinf , and terminal half-life
      were 1.0 +/- 0.32 MUg/mL, 12.6 +/- 5.4 MUg.h/mL, and 18.4 +/- 2.97 hours,
      respectively. On average, venetoclax Cmax and AUCinf values were 94% and 66%
      higher, respectively, in Chinese subjects compared with those observed
      historically for non-Asian subjects receiving the same dose. Based on these
      pharmacokinetic results and the established exposure-response relationship of
      venetoclax in non-Asian CLL subjects, a 400-mg once-daily dosage regimen was
      selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in
      the venetoclax phase 2 open-label study in Chinese subjects with R/R CLL.

PMID- 29058802
TI  - Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration
      via activation of the Wnt/beta-catenin pathway.
AB  - Atherosclerosis is the major cause of stroke and heart disease. However, the
      course and pathogenesis of atherosclerosis remains unknown. The proliferation and
      migration of endothelial cell play important roles in the inition and
      pathological progression of atherosclerosis. In this study, we demonstrated that
      long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) expression
      level was higher in coronary artery disease (CAD) tissues than in normal arterial
      tissues. The expression level of HOTTIP was upregulated in the proliferating
      endothelial cells induced by TNF-alpha or PDGF-BB. Ectopic expression of HOTTIP
      promoted endothelial cell proliferation and also increased the expression of
      proliferating makers cyclin D1 and PCNA. Moreover, elevated expression of HOTTIP
      promoted endothelial cell migration. Downregulation expression of HOTTIP
      suppressed endothelial cell proliferation and migration. Furthermore, we
      determined that overexpression of HOTTIP induced beta-catenin expression and
      enhanced the downstream protein c-Myc expression in the endothelial cell. Ectopic
      expression of HOTTIP increased endothelial cell proliferation and migration via
      activation of the Wnt/beta-catenin pathway. These results suggested that HOTTIP
      might manipulate the endothelial cell proliferation and migration via activation
      of the Wnt/beta-catenin pathway.

PMID- 29058803
TI  - Teaching Geriatric Concepts in Internal Medicine Residency Continuity Clinic Did
      Not Affect Practice.

PMID- 29058805
TI  - Prolidase deficiency in two sisters with recurrent ulcerations of the lower
      extremities.

PMID- 29058804
TI  - Price and Spouse's Coverage in Employee Demand for Health Insurance.

PMID- 29058806
TI  - An 'epidemic' of multiple sclerosis and falling infection rates? Reflecting on
      comparisons made and the rising multiple sclerosis incidence in Bach's 2002 New
      England Journal of Medicine figure.
AB  - BACKGROUND AND PURPOSE: We set out to revisit and comment on the evidence
      surrounding a popular figure published in the New England Journal of Medicine
      (2002), which suggests that the incidence of immune-mediated diseases, including
      multiple sclerosis (MS), is increased by reduced exposure to infections. METHODS:
      Commentary. RESULTS: We found that, to date (May 2017), this influential article
      has been cited >2000 times. However, on close investigation of the figure, we
      noticed some problems. Specifically, we observed several challenges inherent in
      using ecological data from disparate studies and countries to make conclusions
      surrounding the temporal patterns and relationships between diseases. For
      example, the figure depicts incidence data for MS based solely on a limited group
      of individuals with MS (n = 637; 455 women and 182 men) living within the region
      of Sassari on the island of Sardinia, known for its unique genealogy and risk of
      MS. However, the infectious-related data were based primarily on large population
      studies from the USA, with one derived from army recruits in France. CONCLUSIONS:
      We encourage the scientific community to apply rigorous, consistent methods in
      order to confirm or refute whether a strong, direct relationship does or does not
      exist between the incidence of MS and infectious diseases. Further, our article
      highlights a major knowledge gap that would benefit from a thorough review of the
      temporal trends related to MS incidence. Collation of this wide body of knowledge
      may provide a balanced understanding of this important topic and would best serve
      the progress of MS research.

PMID- 29058807
TI  - ABIN1 inhibits HDAC1 ubiquitination and protects it from both proteasome- and
      lysozyme-dependent degradation.
AB  - ABIN1, an important immune regulator, has been shown to be involved in various
      cellular functions, such as immunity, development, tissue homeostasis, and tumor
      progression. It inhibits TNF- and TLR-induced NF-kappaB signaling activation and
      the consequent gene expression. Despite its functional significance, the
      mechanism of ABIN1 in the regulation of various cellular functions remains
      unclear. In this study, we identified HDAC1, a key regulator of eukaryotic gene
      expression and many important cellular events, including cell proliferation,
      differentiation, cancer and immunity, as an interacting partner of ABIN1. The
      results showed that ABIN1 acted as a modulator to down-regulate HDAC1
      ubiquitination via three different linkages, thereby stabilizing HDAC1 by
      inhibiting its lysosomal and proteasomal degradation. Interestingly, the
      inhibitory function of ABIN1 required direct binding with HDAC1. Moreover, the
      level of p53, which was a tumor suppressor and a well-studied substrate of HDAC1,
      was under the regulation of ABIN1 via the modulation of HDAC1 levels, suggesting
      that ABIN1 was physiologically significant in tumor progression. This study has
      revealed a new function of ABIN1 in mediating HDAC1 modification and stability.

PMID- 29058808
TI  - Polypyrrole-coated electrodes show thickness-dependent stability in different
      conditions during 42-day follow-up in vitro.
AB  - Electroconductive polypyrrole/dodecylbenzenesulphonate (PPy/DBS) has been
      proposed as novel electrode coating for biomedical applications. However, as yet,
      little is known about its long-term stability in moist conditions. This study
      compares the stability of PPy/DBS-coated platinum electrodes that are either dry
      stored, incubated, or both incubated and electrically stimulated. The electrical
      and material properties of three different coating thicknesses were monitored for
      42 days. Initially, the PPy/DBS-coating decreased the low frequency impedance of
      the platinum electrodes by 52% to 79%. The dry-stored electrodes remained stable
      during the follow-up, whereas the properties of all the incubated electrodes were
      altered in three stages with thickness-dependent duration: stabilization, stable,
      and degradation. The coated electrodes would be applicable for short-term, low
      frequency in vitro measurements of up to 14 days without electrical stimulation,
      and up to 7 days with stimulation. The coating thickness is bound to other
      coating properties, and should therefore be selected according to the specific
      target application. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 106B: 2202-2213, 2018.

PMID- 29058809
TI  - Combining noninvasive genetics and a new mammalian sex-linked marker provides new
      tools to investigate population size, structure and individual behaviour: An
      application to bats.
AB  - Monitoring wild populations is crucial for their effective management.
      Noninvasive genetic methods provide robust data from individual free-ranging
      animals, which can be used in capture-mark-recapture (CMR) models to estimate
      demographic parameters without capturing or disturbing them. However, sex- and
      status-specific behaviour, which may lead to differences in detection
      probabilities, is rarely considered in monitoring. Here, we investigated
      population size, sex ratio, sex- and status-related behaviour in 19 Rhinolophus
      hipposideros maternity colonies (Northern France) with a noninvasive genetic CMR
      approach (using faeces) combined with parentage assignments. The use of the
      DDX3X/Y-Mam sexual marker designed in this study, which shows inter- and
      intrachromosomal length polymorphism across placental mammals, together with
      eight polymorphic microsatellite markers, produced high-quality genetic data with
      limited genotyping errors and allowed us to reliably distinguish different
      categories of individuals (males, reproductive and nonreproductive females) and
      to estimate population sizes. We showed that visual counts represent well-adult
      female numbers and that population composition in maternity colonies changes
      dynamically during the summer. Before parturition, colonies mainly harbour
      pregnant and nonpregnant females with a few visiting males, whereas after
      parturition, colonies are mainly composed of mothers and their offspring with a
      few visiting nonmothers and males. Our approach gives deeper insight into sex-
      and status-specific behaviour, a prerequisite for understanding population
      dynamics and developing effective monitoring and management strategies. Provided
      sufficient samples can be obtained, this approach can be readily applied to a
      wide range of species.

PMID- 29058810
TI  - miR-302a-3p regulates RANKL expression in human mandibular osteoblast-like cells.
AB  - Receptor activator of nuclear factor kappa-B ligand (RANKL) is important
      substance during osteoclastogenesis that resulted in alveolar bone loss of
      periodontitis. MicroRNAs (miRNAs) regulate gene expression in several biological
      processes including osteoclastogenesis. We investigated the function of microRNA
      302a-3p (miR-302a-3p) to regulate receptor activator of nuclear factor kappa-B
      ligand (RANKL) expression in human mandibular osteoblast-like cells (HMOBs).
      HMOBs were incubated with prostaglandin E2 (PGE2 ) to mimic inflammation, or with
      PGE2 and interferon gamma (IFNgamma) to mimic homeostasis. MicroRNA (miRNA)
      profiles related to RANKL expression were demonstrated by PCR array, and miR-302a
      3p was identified. Using TargetScanHuman 7.0, a target of miR-302a-3p was
      predicted. To confirm its function, miR-302a-3p was overexpressed, or silenced,
      by transfection with miR-302a-3p mimic, or inhibitor, respectively. Level of miR
      302a-3p and RANKL mRNA was assessed by qRT-PCR. Soluble RANKL (sRANKL), and
      membrane-bound RANKL (mRANKL) were measured by ELISA and by Western blot,
      respectively. When PGE2 stimulated RANKL in HMOBs, miR-302a-3p was lower than
      baseline level. However, upregulation of miR-302a-3p is observed when IFNgamma
      suppressed RANKL expression in PGE2 -stimulated HMOBs. miR-302a-3p was predicted
      to target PRKACB mRNA encoding the catalytic subunit in cAMP/PKA pathway.
      Overexpression of miR-302a-3p could decrease RANKL expression during PGE2
      stimulation. In contrast, silencing of miR-302a-3p by its inhibitor increased
      RANKL expression in PGE2 -IFNgamma conditioned HMOBs. miR-302a-3p regulates RANKL
      expression in HMOBs within PGE2 -IFNgamma regulatory network.

PMID- 29058811
TI  - Consumer Perception of Retail Pork Bacon Attributes Using Adaptive Choice-based
      Conjoint Analysis and Maximum Differential Scaling.
AB  - : Bacon is one of the most recognizable consumer pork products and is
      differentiated by appearance, flavor, thickness, and several possible product
      claims. The objective of this study was to explore the attributes of retail bacon
      that influence consumers to purchase and consume bacon. An Adaptive Choice-Based
      Conjoint (ACBC) survey was designed for attributes of raw American-style bacon.
      An ACBC survey (N = 1410 consumers) and Kano questioning were applied to
      determine the key attributes that influenced consumer purchase. Attributes
      included package size, brand, thickness, label claims, flavor, price, and images
      of the bacon package displaying fat:lean ratio. Maximum Difference Scaling
      (MaxDiff) was used to rank appeal of 20 different bacon images with variable
      fat:lean ration and slice shape. The most important attribute for bacon purchase
      was price followed by fat:lean appearance and then flavor. Three consumer
      clusters were identified with distinct preferences. For 2 clusters, price was not
      the primary attribute. Understanding preferences of distinct consumer clusters
      will enable manufacturers to target consumers and make more appealing bacon.
      PRACTICAL APPLICATIONS: Adaptive Choice-Based Conjoint (ACBC) is a research
      technique that allows consumers to react to assembled products and identify
      product attributes that they prefer. Kano questions allow researchers to look at
      the individual aspects of a product and understand consumer sentiment and
      expectations towards those product qualities while Maximum Difference scaling
      allows consumers to directly rank single attributes of a product relative to one
      another. A combination of these 3 approaches can provide key understandings on
      consumer perception of retail bacon allowing companies to optimize and maximize
      their development and advertising resources.

PMID- 29058812
TI  - The effects of Curcumin on HCT-116 cells proliferation and apoptosis via the miR
      491/PEG10 pathway.
AB  - Paternally expressed gene-10 (PEG10) could participate in several carcinomas and
      might be regulated by miR-491. To now, miR-491 was found to play an important
      role in the sensitivity and mechanism of drug usage in the treatment of
      colorectal cancer, and drug resistance is a key factor to affect the disease
      healing. In this study, miR-491, PEG10, Wnt1, and beta-catenin expression levels
      and their correlation with colorectal cancer were assessed in cancer tissues and
      adjacent parts. And the target relationship between PEG10 and miR-491 was
      verified. Meanwhile, the impaction of Curcumin on miR-491, PEG10, and Wnt/beta
      catenin signaling pathway were analyzed in HCT-116 cells. The effects of PEG10
      and Curcumin on human HCT-116 cells proliferation and apoptosis were investigated
      by MTT and flow cytometry assay. Results showed that the expression of miR-491 in
      colon cancer tissues was decreased, but PEG10, Wnt1, and beta-catenin were higher
      than that in adjacent tissues. The PEG10 gene 3' UTR could combine with miR-491
      seed sequence and miR-491 overexpression could cause a decrease in PEG10, Wnt1,
      and beta-catenin levels in human HCT-116 cells. Furthermore, PEG10 overexpression
      increased the expression levels of Wnt1 and beta-catenin, thereby promoting cell
      proliferation and inhibiting apoptosis. In addition, Curcumin could up-regulate
      miR-491, inhibit PEG10, and Wnt/beta-catenin signaling pathway. Consequently,
      Curcumin reduced HCT-116 cells proliferation and promoted cells apoptosis via the
      miR-491/PEG10 pathway. In conclusion, PEG10 was a target gene of miR-491, miR
      491/PEG10 strengthen the sensitivity of Curcumin in HCT-116 cells proliferation
      and apoptosis, which might act as an ideal diagnostic biomarker treatment
      methods.

PMID- 29058813
TI  - Characterization of Terminators in Saccharomyces cerevisiae and an Exploration of
      Factors Affecting Their Strength.
AB  - Terminators in eukaryotes play an important role in regulating the transcription
      process by influencing mRNA stability, translational efficiency, and
      localization. Herein, the strengths of 100 natural terminators in Saccharomyces
      cerevisiae have been characterized by inserting each terminator downstream of the
      TYS1p-enhanced green fluorescent protein (eGFP) reporter gene and measuring the
      fluorescent intensity (FI) of eGFP. Within this library, there are 45 strong
      terminators, 31 moderate terminators, and 24 weak terminators. The strength of
      these terminators, relative to that of PGK1t standard terminator, ranges from
      0.0613 to 1.8002, with a mean relative FI of 0.9945. Mutating the control
      elements of terminators further suggests that the efficiency element has an
      important effect on terminator strength. The use of strong terminators will
      result in an enhanced level of mRNA and protein production; this indicates that
      gene expression can be directly influenced by terminator selection. Pairing a
      terminator with an inducible promoter or a strong constitutive promoter has less
      effect on gene expression; however, pairing with a week promoter will
      significantly increase the level of gene expression. Through exchange of the
      reporter genes, it can be demonstrated that the terminator functions as a genetic
      component and is independent of the coding region. This work demonstrates that
      the terminator is an important regulatory element and can be considered in
      applications for the fine-tuning of gene expression and metabolic pathways.

PMID- 29058814
TI  - New barcoded primers for efficient retrieval of cercozoan sequences in high
      throughput environmental diversity surveys, with emphasis on worldwide biological
      soil crusts.
AB  - We describe the performance of a new metabarcoding approach to investigate the
      environmental diversity of a prominent group of widespread unicellular organisms,
      the Cercozoa. Cercozoa is an immensely large group of protists, and although it
      may dominate in soil and aquatic ecosystems, its environmental diversity remains
      undersampled. We designed PCR primers targeting the hypervariable region V4 of
      the small subunit ribosomal RNA (SSU or 18S) gene, which is the recommended
      barcode marker for Cercozoa. The length of the amplified fragment (c. 350 bp) is
      suitable for Illumina MiSeq, the most cost-effective platform for molecular
      environmental surveys. We provide barcoded primers, an economical alternative to
      multiple libraries for multiplex sequencing of over a hundred samples. In silico,
      our primers matched 68% of the cercozoan sequences of the reference database and
      performed better than previously proposed new-generation sequencing primers. In
      mountain grassland soils and in biological soil crusts from a variety of climatic
      regions, we were able to detect cercozoan sequences encompassing nearly the whole
      range of the phylum. We obtained 901 operational taxonomic units (OTUs) at 97%
      similarity threshold from 26 samples, with c. 50,000 sequences per site, and only
      8% of noncercozoan sequences. We could report a further increase in the diversity
      of Cercozoa, as only 43% of the OTUs were 97%-100% similar to any known sequence.
      Our study thus provides an advanced tool for cercozoan metabarcoding and to
      investigate their diversity and distribution in the environment.

PMID- 29058815
TI  - Differentiation of MSC and annulus fibrosus cells on genetically engineered silk
      fleece-membrane-composites enriched for GDF-6 or TGF-beta3.
AB  - Intervertebral disc (IVD) repair is a high-priority topic in our active and
      increasingly ageing society. Since a high number of people are affected by low
      back pain treatment options that are able to restore the biological function of
      the IVD are highly warranted. Here, we investigated whether the feasibility of
      genetically engineered (GE)-silk from Bombyx mori containing specific growth
      factors to precondition human bone-marrow derived mesenchymal stem cells (hMSC)
      or to activate differentiated human annulus fibrosus cells (hAFC) prior
      transplantation or for direct repair on the IVD. Here, we tested the hypothesis
      that GE-silk fleece can thrive human hMSC towards an IVD-like phenotype. We aimed
      to demonstrate a possible translational application of good manufacturing
      practice (GMP)-compliant GE-silk scaffolds in IVD repair and regeneration. GE
      silk with growth and differentiation factor 6 (GDF-6-silk) or transforming growth
      factor beta3 (TGF-beta3, TGF-beta3-silk) and untreated silk (cSilk) were
      investigated by DNA content, cell activity assay and glycosaminoglycan (GAG)
      content and their differentiation potential by qPCR analysis. We found that all
      silk types demonstrated a very high biocompatibility for both cell types, that
      is, hMSC and hAFC, as revealed by cell activity, and DNA proliferation assay.
      Further, analyzing qPCR of marker genes revealed a trend to differentiation
      toward an NP-like phenotype looking at the Aggrecan/Collagen 2 ratio which was
      around 10:1. Our results support the conclusion that our GE-silk scaffold
      treatment approach can thrive hMSC towards a more IVD-like phenotype or can
      maintain the phenotype of native hAFC. (c) 2017 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:1324-1333, 2018.

PMID- 29058816
TI  - Absolute Bioavailability of Bosutinib in Healthy Subjects From an Open-Label,
      Randomized, 2-Period Crossover Study.
AB  - This study evaluated the absolute bioavailability of bosutinib and assessed its
      safety and tolerability after single-dose oral and intravenous administration. In
      this phase 1 open-label, 2-sequence, 2-period crossover study, healthy, fed
      subjects aged 18-55 years were randomized to 1 of 2 treatment sequences (n =
      7/sequence): oral bosutinib (100 mg * 5) followed by intravenous bosutinib (120
      mg in approximately 240 mL over 1 hour), with a >=14-day washout, or intravenous
      bosutinib and then oral bosutinib. Results of plasma pharmacokinetics analyses
      demonstrated that exposure to intravenous bosutinib was 3-fold higher than for
      oral bosutinib (16.2 and 5.5 ng.h/mL/mg, respectively), and mean terminal half
      life was similar (35.5 and 31.7 hours). The ratio of adjusted geometric means
      (90%CI) for the dose-normalized area under the plasma concentration-time profile
      (AUC0-infinity /D) was 33.85% (30.65%-37.38%). Most treatment-emergent adverse
      events (AEs) were mild in severity. Gastrointestinal (GI) AEs occurred in 9 of 13
      subjects given oral bosutinib, whereas no subjects given intravenous bosutinib
      experienced GI AEs, suggesting bosutinib present in the GI tract had an effect.
      Bosutinib exhibited an absolute bioavailability of 33.85% based on the ratio of
      AUC0-infinity /D. Both oral and intravenous bosutinib were safe and well
      tolerated in healthy, fed adult subjects.

PMID- 29058818
TI  - Prognostic significance of long non-coding RNA MALAT1 for predicting the
      recurrence and metastasis of gallbladder cancer and its effect on cell
      proliferation, migration, invasion, and apoptosis.
AB  - The objective of this study is to explore the role of MALAT1 as a molecular
      indicator in predicting the recurrence, metastasis, and prognosis of gallbladder
      cancer (GBC) and its effect on the proliferation, invasion, migration, and
      apoptosis of GBC cells in vitro. GBC tissues and adjacent normal tissues were
      collected from 102 patients. MALAT1 short hairpin RNA (shRNA) plasmids were first
      constructed to transfect the GBC-SD cells. Reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) was applied to detect MALAT1 expression. CCK
      8 assay, flow cytometry, and Transwell assay were applied to testify the cell
      proliferation, cell cycle, apoptosis, invasion, and migration. A receiver
      operating characteristic (ROC) curve was used to evaluate the values of MALAT1 in
      GBC recurrence, metastasis, and prognosis. COX regression analysis was applied to
      analyze the independent influencing factors of GBC patients' survival status. ROC
      curve results showed that the MALAT1 expression could be a predictor of the GBC
      recurrence, metastasis, and prognosis. According to the COX regression analysis,
      MALAT1 expression, tumor size, and TNM stage were independent influencing factors
      of GBC patients' survival condition. Compared with the GBC-SD cells transfected
      with empty plasmids, those transfected with MALAT1 shRNA plasmids showed higher
      apoptosis rates, weakened proliferation, migration, and invasion. In conclusion,
      our findings demonstrate that lncRNA MALAT1 can be considered as an indicator for
      evaluating the recurrence, metastasis, and prognosis of GBC patients. We also
      demonstrate how the overexpression of MALAT1 confers an oncogenic function in
      GBC.

PMID- 29058817
TI  - Dasatinib cessation after deep molecular response exceeding 2 years and natural
      killer cell transition during dasatinib consolidation.
AB  - Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic
      myelogenous leukemia (CML) by inducing substantial deep molecular responses
      (DMR); some patients have successfully discontinued TKI therapy after maintaining
      DMR for >=1 year. In this cessation study, we investigated the optimal conditions
      for dasatinib discontinuation in patients who maintained DMR for >=2 years. This
      study included 54 patients with CML who were enrolled in a D-STOP multicenter
      prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year
      consolidation. Peripheral lymphocyte profiles were analyzed by flow cytometry.
      The estimated 12-month treatment-free survival (TFS) was 62.9% (95% confidence
      interval: 48.5%-74.2%). During dasatinib consolidation, the percentage of total
      lymphocytes and numbers of CD3- CD56+ natural killer (NK) cells, CD16+ CD56+ NK
      cells and CD56+ CD57+ NK-large granular lymphocytes (LGL) were significantly
      higher in patients with molecular relapse after discontinuation but remained
      unchanged in patients without molecular relapse for >7 months. At the end of
      consolidation, patients whose total lymphocytes comprised <41% CD3- CD56+ NK
      cells, <35% CD16+ CD56+ NK cells, or <27% CD56+ CD57+ NK-LGL cells had higher TFS
      relative to other patients (77% vs 18%; P < .0008; 76% vs 10%; P < .0001; 84% vs
      46%; P = .0059, respectively). The increase in the number of these NK cells
      occurred only during dasatinib consolidation. In patients with DMR, dasatinib
      discontinuation after 2-year consolidation can lead to high TFS. This outcome
      depends significantly on a smaller increase in NK cells during dasatinib
      consolidation.

PMID- 29058819
TI  - Involvement of dying beta cell originated messenger molecules in differentiation
      of pancreatic mesenchymal stem cells under glucotoxic and glucolipotoxic
      conditions.
AB  - Beta cell mass regulation represents a critical issue for understanding and
      treatment of diabetes. The most important process in the development of diabetes
      is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and
      the regeneration mechanism of new beta cells that will replace dead beta cells is
      still not fully understood. The aim of this study was to investigate the
      generation mechanism of new beta cells by considering the compensation phase of
      type 2 diabetes mellitus. In this study, pancreatic islet derived mesenchymal
      stem cells (PI-MSCs) were isolated from adult rats and characterized. Then, beta
      cells isolated from rats were co-cultured with PI-MSCs and they were exposed to
      glucotoxicity, lipotoxicity and glucolipotoxicity conditions for 72 hr. As the
      results apoptotic and necrotic cell death were increased in both PI-MSCs and beta
      cells especially by the exposure of glucotoxic and glucolipotoxic conditions to
      the co-culture systems. Glucotoxicity induced-differentiated beta cells were
      functional due to their capability of insulin secretion in response to rising
      glucose concentrations. Moreover, beta cell proliferation was induced in the
      glucotoxicity-treated co-culture system whereas suppressed in lipotoxicity or
      glucolipotoxicity-treated co-culture systems. In addition, 11 novel proteins,
      that may release from dead beta cells and have the ability to stimulate PI-MSCs
      in the direction of differentiation, were determined in media of glucotoxicity or
      glucolipotoxicity-treated co-culture systems. In conclusion, these molecules were
      considered as important for understanding cellular mechanism of beta cell
      differentiation and diabetes. Thus, they may be potential targets for diagnosis
      and cellular or therapeutic treatment of diabetes.

PMID- 29058820
TI  - Anterior colporrhaphy plus inside-out tension-free vaginal tape for associated
      stress urinary incontinence and cystocele: 10-year follow up results.
AB  - AIMS: We report the success rate and complications rate of combined ultralateral
      anterior Colporrhaphy plus Tension-free Vaginal Tape (TVT-O) in a long-term (10
      year) follow-up prospective survey. METHODS: Patients previously treated for
      associated stress urinary incontinence (SUI) and cystocele were subjected to
      annual follow-up for 10 year with a complete urogynecologic evaluation.
      Furthermore, an urodynamic assessment and a quality of life questionnaire (ICIQ
      UI SF) were recorded at the 5th and 10th year of follow up. RESULTS: Fifty
      patients treated between June 2004 and May 2006 were included in the analysis.
      Five patients did not return to 5-yr follow-up: two patients developed a median
      tape erosion and three patients withdraw. At 10-yr follow-up two more patients
      withdraw for a total of seven patients lost to follow-up. After 10 years patients
      objectively cured from cystocele were 41 (95%) while patients objectively cured
      from SUI were 39 (91%). At 10th year follow-up 38 patients (89%) result cured
      from both SUI and cystocele, 3 (7%) patients result cured only from prolapse, 1
      (2%) patient only from SUI, and 1 (2%) patient result objectively failed for both
      SUI and cystocele. The ICIQ-UI SF scores at 10th year follow-up was 6.2 +/- 3.7.
      The late complication rate at 10th year follow-up was 32% (OAB symptoms 20%;
      Mixed incontinence 2%; Bladder outlet obstruction 0%; Dyspareunia 6%; Chronic
      pelvic pain 0%; Vaginal tape erosion 4%; Detrusor hyperactivity 0%). CONCLUSIONS:
      The combined procedures shown proved to be an effective and safe procedure to
      treat concomitant SUI and cystocele.

PMID- 29058821
TI  - A Thorough QT Study to Evaluate the Effects of Supratherapeutic Doses of
      Ledipasvir on the QTc Interval in Healthy Subjects.
AB  - This study evaluated the effect of supratherapeutic exposure of the anti-HCV drug
      ledipasvir on the QTc interval in healthy subjects. Sixty healthy volunteers were
      randomized to receive twice-daily blinded ledipasvir (120 mg) or placebo,
      administered for 10 days each, or single doses of open-label moxifloxacin (400
      mg). Serial plasma samples for ledipasvir concentration analysis were collected
      after each treatment. Triplicate time-matched electrocardiograms were collected
      at baseline and after each treatment. Change from baseline in the QTc for
      ledipasvir or moxifloxacin versus placebo was determined using several correction
      formulas (primary: QTcF [Fridericia's]; secondary: QTcN [population] and QTcI
      [individual]). Pharmacokinetics and exposure-QTc relationships were evaluated.
      Ledipasvir AUC0-24 and Cmax achieved approximately 3.7-fold and 4.2-fold,
      respectively, above exposures observed following administration of
      ledipasvir/sofosbuvir (90/400 mg) to HCV-infected patients. There was a lack of
      effect of supratherapeutic ledipasvir on QTc intervals using all correction
      methods (upper bound of the 2-sided 90%CIs for the mean difference in time
      matched baseline-corrected QTc between ledipasvir versus placebo < 10
      milliseconds at all times). The lower bound of the 2-sided 96.67%CI for the mean
      difference in moxifloxacin versus placebo was >5 milliseconds, thereby
      establishing assay sensitivity. Categorical analyses did not demonstrate
      clinically relevant effects of ledipasvir on QTc intervals or other
      electrocardiogram parameters. No relationships between ledipasvir plasma
      concentration and QTc interval were observed. Ledipasvir does not prolong QTc
      interval. Based on these results and a previous TQT evaluation for sofosbuvir,
      the fixed-dose combination regimen of ledipasvir/sofosbuvir is not expected to
      prolong the QTc interval.

PMID- 29058822
TI  - Omalizumab rapidly improves angioedema-related quality of life in adult patients
      with chronic spontaneous urticaria: X-ACT study data.
AB  - BACKGROUND: The X-ACT study aimed to examine the effect of omalizumab treatment
      on quality of life (QoL) in chronic spontaneous urticaria (CSU) patients with
      angioedema refractory to high doses of H1 -antihistamines. METHODS: In X-ACT, a
      phase III, double-blind, placebo-controlled study, CSU patients (18-75 years)
      with >=4 angioedema episodes during the 6 months before inclusion were randomized
      (1:1) to receive omalizumab 300 mg or placebo every 4 weeks for 28 weeks.
      Angioedema-related QoL, skin-related QoL impairment, and psychological well-being
      were assessed. RESULTS: Ninety-one patients were randomized and 68 (omalizumab, n
      = 35; placebo, n = 33) completed the 28-week treatment period. At baseline, the
      mean (SD) total Angioedema QoL (AE-QoL; 56.2 [18.7] and 59.9 [19.2]) and
      Dermatology Life Quality Index (DLQI; 14.6 [5.7] and 16.6 [7.3]) score were high
      in the omalizumab and placebo group, respectively. At Week 4 (after the first
      treatment), the least squares mean difference in the AE-QoL and DLQI score
      between groups was -17.6 (P < .001) and -7.2 (P < .001), respectively.
      Significant QoL improvements in the omalizumab vs placebo groups continued until
      Week 28, but returned to placebo levels at the follow-up visit. The mean (SD)
      baseline 5-item World Health Organization Well-being Index was 10.0 (5.5,
      omalizumab) and 7.7 (5.3, placebo), which increased above the depression
      threshold (<13) from Week 4 and throughout with omalizumab but not placebo
      treatment. Compared to placebo, omalizumab was also associated with decreased
      fear of suffocation due to angioedema. CONCLUSIONS: Our findings support
      omalizumab treatment in patients with severe H1-antihistamine-refractory CSU with
      angioedema.

PMID- 29058823
TI  - Single-dose bone pharmacokinetics of vancomycin in a porcine implant-associated
      osteomyelitis model.
AB  - The increasing incidence of orthopaedic methicillin-resistant Staphylococcus
      aureus (MRSA) infections represents a significant therapeutic challenge. Being
      effective against MRSA, the role of vancomycin may become more important in the
      orthopaedic setting in the years to come. Nonetheless, vancomycin bone and soft
      tissue penetration during infection remains unclear. In eight pigs, implant
      associated osteomyelitis was induced on day 0, using a Staphylococcus aureus
      strain. Following administration of 1,000 mg of vancomycin on day 5, vancomycin
      concentrations were obtained with microdialysis for 8 h in the implant bone
      cavity, in cancellous bone adjacent to the implant cavity, in subcutaneous
      adipose tissue (SCT) adjacent to the implant cavity, and in healthy cancellous
      bone and healthy SCT in the contralateral leg. Venous blood samples were also
      obtained. The extent of infection and inflammation was evaluated by post-mortem
      computed tomography scans, C-reactive protein serum levels and cultures of blood
      and swabs. In relation to all the implant cavities, bone destruction was found.
      Ranging from 0.20 to 0.74, tissue penetration, expressed as the ratio of the area
      under the concentration-time curve from 0 to the last measured value, was
      incomplete for all compartments except for healthy SCT. The lowest penetration
      was found in the implant cavity. In conclusion, Staphylococcus aureus implant
      associated osteomyelitis was found to reduce vancomycin bone penetration,
      especially in the implant cavity. These findings suggest that it may be unsafe to
      rely solely on vancomycin therapy when treating acute osteomyelitis. Particularly
      when metaphyseal cavities are present, surgical debridement seems necessary. (c)
      2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 36:1093-1098, 2018.

PMID- 29058825
TI  - Structure Formation in Soft-Matter Solutions Induced by Solvent Evaporation.
AB  - Solvent evaporation in soft-matter solutions (solutions of colloidal particles,
      polymers, and their mixtures) is an important process in material making and in
      the printing and coating industries. The solvent-evaporation process determines
      the structure of materials and strongly affects their performance. Solvent
      evaporation involves many physicochemical processes: flow, diffusion,
      crystallization, gelation, glass transition, etc. and is quite complex. Here,
      recent progress in this important process is reported, with a special focus on
      theoretical and simulation studies.

PMID- 29058824
TI  - Synthesis and Biological Evaluation of Stilbene Analogues as Hsp90 C-Terminal
      Inhibitors.
AB  - The design, synthesis, and biological evaluation of stilbene-based novobiocin
      analogues is reported. Replacement of the biaryl amide side chain with a triazole
      side chain produced compounds that exhibited good antiproliferative activities.
      Heat shock protein 90 (Hsp90) inhibition was observed when N-methylpiperidine was
      replaced with acyclic tertiary amines on the stilbene analogues that also contain
      a triazole-derived side chain. These studies revealed that ~24 A is the optimal
      length for compounds that exhibit good antiproliferative activity as a result of
      Hsp90 inhibition.

PMID- 29058827
TI  - Stakeholder value-linked sustainability assessment: Evaluating remedial
      alternatives for the Portland Harbor Superfund Site, Portland, Oregon, USA.
AB  - Regulatory decisions on remediation should consider affected communities' needs
      and values, and how these might be impacted by remedial options; this process
      requires that diverse stakeholders are able to engage in a transparent
      consideration of value trade-offs and of the distribution of risks and benefits
      associated with remedial actions and outcomes. The Stakeholder Values Assessment
      (SVA) tool was developed to evaluate remedial impacts on environmental quality,
      economic viability, and social equity in the context of stakeholder values and
      priorities. Stakeholder values were linked to the pillars of sustainability and
      also to a range of metrics to evaluate how sediment remediation affects these
      values. Sediment remedial alternatives proposed by the US Environmental
      Protection Agency (USEPA) for the Portland Harbor Superfund Site were scored for
      each metric, based upon data provided in published feasibility study (FS)
      documents. Metric scores were aggregated to generate scores for each value; these
      were then aggregated to generate scores for each pillar of sustainability. In
      parallel, the inferred priorities (in terms of regional remediation, restoration,
      planning, and development) of diverse stakeholder groups (SGs) were used to
      evaluate the sensitivity and robustness of the values-based sustainability
      assessment to diverse SG priorities. This approach, which addresses social
      indicators of impact and then integrates them with indicators of environmental
      and economic impacts, goes well beyond the Comprehensive Environmental Response,
      Compensation and Liability Act's (CERCLA) 9 criteria for evaluating remedial
      alternatives because it evaluates how remedial alternatives might be ranked in
      terms of the diverse values and priorities of stakeholders. This approach
      identified trade-offs and points of potential contention, providing a systematic,
      semiquantitative, transparent valuation tool that can be used in community
      engagement. Integr Environ Assess Manag 2018;14:43-62. (c) 2017 The Authors.
      Integrated Environmental Assessment and Management published by Wiley
      Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry
      (SETAC).

PMID- 29058826
TI  - Cathepsin K activity controls cardiotoxin-induced skeletal muscle repair in mice.
AB  - BACKGROUND: Cathepsin K (CatK) is a widely expressed cysteine protease that has
      gained attention because of its enzymatic and non-enzymatic functions in
      signalling. Here, we examined whether CatK-deficiency (CatK-/- ) would mitigate
      injury-related skeletal muscle remodelling and fibrosis in mice, with a special
      focus on inflammation and muscle cell apoptosis. METHODS: Cardiotoxin (CTX, 20
      MUM/200 MUL) was injected into the left gastrocnemius muscle of male wild-type
      (CatK+/+ ) and CatK-/- mice, and the mice were processed for morphological and
      biochemical studies. RESULTS: On post-injection Day 14, CatK deletion ameliorated
      muscle interstitial fibrosis and remodelling and performance. At an early time
      point (Day 3), CatK-/- reduced the lesion macrophage and leucocyte contents and
      cell apoptosis, the mRNA levels of monocyte chemoattractant protein-1, toll-like
      receptor-2 and toll-like receptor-4, and the gelatinolytic activity related to
      matrix metalloproteinase-2/-9. CatK deletion also restored the protein levels of
      caspase-3 and cleaved caspase-8 and the ratio of the BAX to the Bcl-2. Moreover,
      CatK deficiency protected muscle fibre laminin and desmin disorder in response to
      CTX injury. These beneficial muscle effects were mimicked by CatK-specific
      inhibitor treatment. In vitro experiments demonstrated that pharmacological CatK
      inhibition reduced the apoptosis of C2C12 mouse myoblasts and the levels of BAX
      and caspase-3 proteins induced by CTX. CONCLUSIONS: These results demonstrate
      that CatK plays an essential role in skeletal muscle loss and fibrosis in
      response to CTX injury, possibly via a reduction of inflammation and cell
      apoptosis, suggesting a novel therapeutic strategy for the control of skeletal
      muscle diseases by regulating CatK activity.

PMID- 29058828
TI  - How Large Can We Build a Cyclic Assembly? Impact of Ring Size on Chelate
      Cooperativity in Noncovalent Macrocyclizations.
AB  - Self-assembled systems rely on intramolecular cooperative effects to control
      their growth and regulate their shape, thus yielding discrete, well-defined
      structures. However, as the size of the system increases, cooperative effects
      tend to dissipate. We analyze here this situation by studying a set of oligomers
      of different lengths capped with guanosine and cytidine nucleosides, which
      associate in cyclic tetramers by complementary Watson-Crick H-bonding
      interactions. As the monomer length increases, and thus the number of C(sp)-C(sp2
      ) sigma-bonds in the pi-conjugated skeleton, the macrocycle stability decreases
      due to a notable reduction in effective molarity (EM), which has a clear entropic
      origin. We determined the relationship between EM or DeltaS and the number of
      sigma-bonds, which allowed us to predict the maximum monomer lengths at which
      cyclic species would still assemble quantitatively, or whether the cyclic species
      would not able to compete at all with linear oligomers over the whole
      concentration range.

PMID- 29058829
TI  - Large-Scale Fabrication of Core-Shell Structured C/SnO2 Hollow Spheres as Anode
      Materials with Improved Lithium Storage Performance.
AB  - Due to the high theoretical capacity as high as 1494 mAh g-1 , SnO2 is considered
      as a potential anode material for high-capacity lithium-ion batteries (LIBs).
      Therefore, the simple but effective method focused on fabrication of SnO2 is
      imperative. To meet this, a facile and efficient strategy to fabricate core-shell
      structured C/SnO2 hollow spheres by a solvothermal method is reported. Herein,
      the solid and hollow structure as well as the carbon content can be controlled.
      Very importantly, high-yield C/SnO2 spheres can be produced by this method, which
      suggest potential business applications in LIBs field. Owing to the dual buffer
      effect of the carbon layer and hollow structures, the core-shell structured
      C/SnO2 hollow spheres deliver a high reversible discharge capacity of 1007 mAh g
      1 at a current density of 100 mA g-1 after 300 cycles and a superior discharge
      capacity of 915 mAh g-1 at 500 mA g-1 after 500 cycles. Even at a high current
      density of 1 and 2 A g-1 , the core-shell structured C/SnO2 hollow spheres
      electrode still exhibits excellent discharge capacity in the long life cycles.
      Consideration of the superior performance and high yield, the core-shell
      structured C/SnO2 hollow spheres are of great interest for the next-generation
      LIBs.

PMID- 29058831
TI  - JCD Editorial - June, 2017.

PMID- 29058830
TI  - Clinical efficacy of utilizing Ultrapulse CO2 combined with fractional CO2 laser
      for the treatment of hypertrophic scars in Asians-A prospective clinical
      evaluation.
AB  - BACKGROUND AND OBJECTIVE: Hypertrophic scarring is seen regularly. Tissue
      penetration of laser energy into hypertrophic scars using computer defaults from
      some lasers may be insufficient and penetration not enough. We have developed a
      treatment with an interrupted laser "drilling" by the Ultrapulse CO2 (Manual
      Fractional Technology, MFT) and, a second pass, with fractional CO2 . The MFT
      with fractional CO2 lasers to treat hypertrophic scars is evaluated. STUDY
      DESIGN/MATERIALS AND METHODS: A total of 158 patients with hypertrophic scars had
      three sessions of MFT with fractional CO2 laser at 3-month intervals. Evaluations
      made before and 6 months after the 3rd treatment: (1) the Vancouver Scar Scale
      (VSS), (2) the University of North Carolina (UNC) Scar Scale, and (3) a survey of
      patient satisfaction. RESULTS: All data were analyzed using a t-test before and
      after treatment. The VSS score decreased from 9.35 to 3.12 (P<.0001), and the UNC
      Scar Scale score decreased from 8.03 to 1.62 (P<.0001). The overall satisfaction
      rate was 92%. No long-term complications occurred in the clinical trial.
      CONCLUSION: The interrupted laser drilling by MFT and a fractional CO2 laser had
      profound effects on the hypertrophic scars treated. It works by increasing the
      penetration depth of the CO2 laser in the scar tissue, exerting more precise
      effects on the hypertrophic scars. MFT combined with fractional CO2 laser has the
      potential to be a major advance in the treatment of hypertrophic scars.

PMID- 29058832
TI  - [Image of the month: Travel souvenir].

PMID- 29058833
TI  - [Upper extremity deep venous effort thrombosis : management of the Paget
      Schroetter syndrome in the emergency department].
AB  - We report a case of upper extremity deep venous effort thrombosis complicating a
      thoracic outlet syndrome in a 44-year-old patient. The appearance of this
      complication was sudden. A clinical examination followed by imaging with
      phlebography leads to a quick diagnosis. Effort thrombosis is a classic example
      of an entity which, if treated correctly, has minimal long-term sequelae but, if
      ignored, is associated with significant long-term morbidity. An appropriate
      medical and interventional care has been implemented as soon as possible. Once
      primary thrombosis is recognized, catheter-directed thrombolytic therapy is
      usually successful if initiated early, but often unmasks an underlying problem.

PMID- 29058834
TI  - [Difficult diagnosis of Erdheim Chester disease revealed by central diabetes
      insipidus].
AB  - The Erdheim Chester disease is a rare form of non Langerhans cell histiocytosis.
      Its rarity and its unspecific clinical presentation, make that its diagnosis is
      often delayed. We report the case of a 50 years old female who has an Erdheim
      Chester disease, revealed by a central diabetes insipidus with thickening of the
      pituitary stalk, with associated gonadotropin deficiency. The Erdheim Chester
      disease was suspected because of the association with other evocative systemic
      lesions: eyelid xanthelasmas and bone lesions in metaphyseal-diaphyseal region of
      the upper and lower ends of both femurs and tibias on bone scan. Confirmation of
      the diagnosis was initially difficult and delayed, with initially inconclusive
      cutaneous and bone biopsies. It is the histological re-reading with
      immunohistochemical study of the bone biopsies which allowed the diagnosis by
      showing histiocytes positive for the CD68 and negative for the CD1a and the
      protein S100. The diagnosis was made with a delay of 3 years. In conclusion,
      although rare, Erdheim Chester disease should be suspected in front of a set of
      clinical and radiological arguments. Diagnostic confirmation is based on
      histological and especially immunohistochemical studies.

PMID- 29058835
TI  - [Diabetes and Ramadan : consequences of fasting and practical aspects of
      management].
AB  - A lot of diabetic Muslims choose to fast during Ramadan, despite recommendations
      that advise some patients to abstain according to established risk factors.
      Fasting exposes the diabetic subject to acute major complications, including
      diabetic ketoacidosis and severe hypoglycaemia. Patients with diabetes,
      therefore, had to benefit from individualized care already before Ramadan,
      including a risk assessment, a specific education integrating in particular the
      adaptation of the pharmacological treatment in order to limit the occurrence of
      these acute complications.

PMID- 29058836
TI  - [The major SCAR syndromes].
AB  - Some drug eruptions are frequent and follow an indolent course, while others
      prove to be life-threatening. By contrast, SCAR syndromes are serious skin drug
      reactions that are rare but their vital prognosis is affected. The three distinct
      entities of importance are the former Lyell's syndrome, now identified as SJS-TEN
      syndrome (Stevens-Johnson syndrome/toxic epidermal necrolysis), the DRESS
      syndrome (drug reaction with eosinophilia and systemic symptoms), and the AGEP
      syndrome (acute generalized exanthematous pustulosis).

PMID- 29058837
TI  - [Oxynorm(r) instant versus Tradonal(r) odis as level 2 analgesic in an emergency
      service : a monocentric double blind randomized non-inferiority study].
AB  - Pain is one of the most common reasons for consultation in the ER. As far as
      class II analgesics are concerned, tramadol is most usually used. According to
      some data from the literature, it would seem that oxycodone and tramadol are
      equivalent in terms of analgesia. We have tried to prove that oxycodone
      (Oxynorm(r) instant) is not less effective than tramadol (Tradonal(r) odis) in an
      emergency unit. This is a prospective, monocentric, randomized study carried out
      amongst ambulatory patients. Those included in the study were given 1 g of
      paracetamol and a weight-ajusted dose of either tramadol or oxycodone. Every 30
      minutes, a simple numerical scale (NS) was established and the clinical
      parameters were checked. We studied a total of 121 patients divided into 2
      groups. There is an average difference of -1.47 between the average ?NS of the
      oxycodone group and the average ?NS of the tramadol group, with a confidence
      interval of 95 % (-9.42 - 6.48). The confidence interval does not cross the -10
      line considered as the acceptable loss of efficiency, which allows us to conclude
      that oxycodone is not inferior to tramadol. As far as the adverse effects studied
      are concerned, there is no significant link between the treatment and the
      appearance of any side effect.

PMID- 29058839
TI  - [Cone Beam CT New tool in diagnostic imaging].
AB  - The goal of this article is to show the advantages of the Cone Beam Computerized
      Tomography (CBCT) compared to classical Computerized Tomography (CT) and to
      describe several clinical applications of interest with this rather new
      technology. Invented practically for dentistry, in particular in implantology,
      the CBCT found major indications in paranasal sinus imaging, in maxillofacial and
      oral surgery, in periodontology, endodontics and orthodontics. CBCT is very
      useful to characterize various lesions of jaws with a reserve concerning the
      study of soft tissues (in that case, an MRI or CT with contrast injection should
      be preferred). Recently, CBCT is more and more used for temporal bone imaging and
      studies of small peripheral articulations.

PMID- 29058838
TI  - [Early implantation of a penile prosthesis as an optimal treatment of retractory
      low flow priapism].
AB  - Low flow priapism is a urologic emergency because it leads to erectile
      dysfunction due to cavernosal fibrosis. Several treatments exist, including
      cavernosal aspiration, washing with or without alpha-mimetic agent or shunting
      surgery. In case of failure of these methods or prolonged priapism (superior to
      36 hours), the option of early penile prostheses implantation should be discussed
      with a motivated patient in order to improve sexual satisfaction.

PMID- 29058840
TI  - [Use of oral glucose-lowering agents in patients with renal impairment].
AB  - Patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) are
      increasingly numerous, especially in the elderly population. Surprisingly, this
      situation is often under-recognized or even neglected in clinical practice. Yet,
      most oral antidiabetic (OAD) agents have limitations in case of renal impairment,
      either because they require a dose reduction, or are contra-indicated mainly for
      safety reasons. This clinical case gives the opportunity to discuss the
      modalities of prescription and cautions to be taken when using most commonly
      prescribed OAD, metformin, insulin secretagogues (sulfonylureas, repaglinide),
      DPP-4 inhibitors (gliptins) and SGLT2 inhibitors, in a patient with T2D and CKD.

PMID- 29058841
TI  - Tech Trends. A look into the latest dental and general technology on the market.

PMID- 29058842
TI  - Evaluating Alternative Approaches to Incremental Health-Insurance Expansion.

PMID- 29058843
TI  - A New Approach to Risk-Spreading via Coverage-Expansion Subsidies.

PMID- 29058844
TI  - Reinsuring Risk to Increase Access to Health Insurance.

PMID- 29058846
TI  - The Importance of Group Coverage: How Tax Policy Shaped U.S. Health Insurance.

PMID- 29058845
TI  - The mobility of elite life scientists: Professional and personal determinants
AB  - As scientists' careers unfold, mobility can allow researchers to find
      environments where they are more productive and more effectively contribute to
      the generation of new knowledge. In this paper, we examine the determinants of
      mobility of elite academics within the life sciences, including individual
      productivity measures and for the first time, measures of the peer environment
      and family factors. Using a unique data set compiled from the career histories of
      10,051 elite life scientists in the U.S., we paint a nuanced picture of mobility.
      Prolific scientists are more likely to move, but this impulse is constrained by
      recent NIH funding. The quality of peer environments both near and far is an
      additional factor that influences mobility decisions. We also identify a
      significant role for family structure. Scientists appear to be unwilling to move
      when their children are between the ages of 14-17, and this appears to be more
      pronounced for mothers than fathers. These results suggest that elite scientists
      find it costly to disrupt the social networks of their children during
      adolescence and take these costs into account when making career decisions.

PMID- 29058847
TI  - Socioeconomic Status and Child Health: Why Is the Relationship Stronger for Older
      Children?

PMID- 29058849
TI  - Doing Our Part.

PMID- 29058850
TI  - The Argument From Perfection.

PMID- 29058851
TI  - Stem Cell Delivery Approach Regenerates Dental Pulp-Like Tissue in Rats.

PMID- 29058852
TI  - Mouth Cancer Rates in UK Soar.

PMID- 29058853
TI  - Patients Should Stop e-Cigarette Use Before Plastic Surgery.

PMID- 29058854
TI  - Study Concludes Most Nursing Home Patients Refuse Dental Care.

PMID- 29058855
TI  - Crown Lengthening Needs and Outcomes in Adults Attending a Predoctoral Clinic.
AB  - In this retrospective study of 5,536 patients admitted over four yearsat a
      predoctoral dental clinic for comprehensive care, general dentists
      identifiedcrown lengthening needs in 584 patients and 760 teeth. Only 51 patients
      and68 teeth actually received crown lengthening procedures. For the other
      cases,patients discontinued treatment or chose extraction or restoration without
      crownlengthening procedures. Teeth that received crown lengthening procedures
      weremost likely restored and functioning for at least one year.

PMID- 29058856
TI  - Giant Cell Tumor of Mandibular Condyle: A Rarity.

PMID- 29058858
TI  - Final Notice: Sending an Account to Collections.

PMID- 29058857
TI  - California Dentists' Opinions of the Interface Between Oral and Overall Health.
AB  - This cross-sectional study investigated California dentists' knowledgeand opinion
      of the interface between oral and overall health. A questionnaire andcover letter
      explaining the purpose of the study were mailed to 1,100 randomlyselected
      California licensed general dentists. The survey measured dentists'knowledge and
      opinions of the interface between oral and overall health as well astheir
      recommendations for strengthening this interface. Dentists believed that therewas
      minimal interface between oral and overall health care.

PMID- 29058859
TI  - Don't Get Caught by Phishing

PMID- 29058860
TI  - Tech Trends. A look into the latest dental and general technology on the market.

PMID- 29058861
TI  - Dr. Bob: Worm's Eye View.

PMID- 29058862
TI  - It's Time to Stop Using Bite Marks in Forensics, Experts Argue.

PMID- 29058863
TI  - Participative Facility Planning for Obstetrical and Neonatal Care Processes:
      Beginning of Life Process
AB  - Introduction: Old hospitals may promote inefficient patient care processes and
      safety. A new, functionally planned hospital presents a chance to create an
      environment that supports streamlined, patient-centered healthcare processes and
      adapts to users' needs. This study depicts the phases of a facility planning
      project for pregnant women and newborn care processes (beginning of life process)
      at Turku University Hospital. Materials and Methods: Project design reports and
      meeting documents were utilized to assess the beginning of life process as well
      as the work processes of the Women's and Children's Hospital. Results: The main
      elements of the facility design (FD) project included rigorous preparation for
      the FD phase, functional planning throughout the FD process, and setting key
      values: (1) family-centered care, (2) Lean thinking and Lean tools as the
      framework for the FD process, (3) safety, and (4) cooperation. Conclusions: A
      well-prepared FD project with sufficient insight into functional planning, Lean
      thinking, and user-centricity seemed to facilitate the actual FD process.
      Although challenges occurred, the key values were not forgone and were
      successfully incorporated into the new hospital building.

PMID- 29058864
TI  - Controllable Self-Assembly of Micro-Nanostructured Si-Embedded Graphite/Graphene
      Composite Anode for High-Performance Li-Ion Batteries.
AB  - Si-containing graphite-based composites are considered as promising high-capacity
      anodes for lithium-ion batteries (LIBs). Here, a controllable and scalable self
      assembly strategy is developed to produce micro-nanostructured
      graphite/Si/reduced graphene oxides composite (SGG). The self-assembly procedure
      is realized by the hydrogen bond interaction between acylamino-modified graphite
      and graphene oxides (GO); Si nanoparticles are in situ embedded between graphite
      and GO sheets uniformly. This architecture is able to overcome the
      incompatibility between Si nanoparticles and microsized graphite. Accordingly,
      the as-prepared SGG anode (Si 8 wt %) delivers a reversible Li-storage capacity
      of 572 mAh g-1 at 0.2 C, 502.2 mAh g-1 after 600 cycles at 0.8 C with a retention
      of 92%, and a capacity retention of 64% even at 10 C. The impressive
      electrochemical properties are ascribed to the stable architecture and three
      dimensional conductive network constructed by graphite and graphene sheets, which
      can accommodate the huge volume change of Si, keep the conductive contact and
      structural integrity, and suppress side reactions with electrolyte. Additionally,
      the full-cell (LiFePO4 cathode/SGG anode) delivers a specific capacity of 550 mAh
      g-1 with a working potential beyond 3.0 V.

PMID- 29058866
TI  - Is There a Threshold in the Antibacterial Action of Superhydrophobic Surfaces?
AB  - The realization of antibacterial surfaces is an important scientific problem,
      which may be addressed by the use of superhydrophobic surfaces, reducing
      bacterial adhesion. However, there are several limitations and contradicting
      reports on the antibacterial efficacy of such surfaces. Moreover, achieving
      antibacterial action through minimization of adhesion does not ensure complete
      protection against bacteria. Here, we identify the important factors affecting
      antibacterial action on superhydrophobic surfaces, emphasizing the role of
      bacterial concentration, and observing an upper concentration threshold above
      which antibacterial action of any surface is compromised. Finally, we propose
      metal enriched, superhydrophobic surfaces, as the "ultimate" "hybrid"
      antibacterial surfaces for in vitro applications.

PMID- 29058865
TI  - Melanocortin-1 Receptor-Targeting Ultrasmall Silica Nanoparticles for Dual
      Modality Human Melanoma Imaging.
AB  - The poor prognosis associated with malignant melanoma has not changed
      substantially over the past 30 years. Targeted molecular therapies, such as
      immunotherapy, have shown promise but suffer from resistance and off-target
      toxicities, underscoring the need for alternative therapeutic strategies that can
      be used in combination with existing protocols. Moreover, peptides targeting
      melanoma-specific markers, like the melanocortin-1 receptor (MC1-R), for imaging
      and therapy exhibit high renal uptake that limits clinical translation. In the
      current study, the application of ultrasmall fluorescent (Cy5) silica
      nanoparticles (C' dots), conjugated with MC1-R targeting alpha melanocyte
      stimulating hormone (alphaMSH) peptides on the polyethylene glycol (PEG) coated
      surface, is examined for melanoma-selective imaging. alphaMSH peptide sequences,
      evaluated for conjugation to the PEG-Cy5-C' dot nanoparticles, bound to MC1-R
      with high affinity and targeted melanoma in syngenetic and xenografted melanoma
      mouse models. Results demonstrated a 10-fold improvement in MC1-R affinity over
      the native peptide alone following surface attachment of the optimal alphaMSH
      peptide. Systematic in vivo studies further demonstrated favorable in vivo renal
      clearance kinetics as well as receptor-mediated tumor cell internalization of as
      developed radiolabeled particle tracers in B16F10 melanoma bearing mice. These
      findings highlight the ability of alphaMSH-PEG-Cy5-C' dots to overcome previous
      hurdles that prevented clinical translation of peptide and antibody-based
      melanoma probes and reveal the potential of alphaMSH-PEG-Cy5-C' dots for melanoma
      selective imaging, image-guided surgery, and therapeutic applications.

PMID- 29058867
TI  - Directionally Aligned Amorphous Polymer Chains via Electrohydrodynamic-Jet
      Printing: Analysis of Morphology and Polymer Field-Effect Transistor
      Characteristics.
AB  - Electrohydrodynamic-jet (EHD-jet) printing provides an opportunity to directly
      assembled amorphous polymer chains in the printed pattern. Herein, an EHD-jet
      printed amorphous polymer was employed as the active layer for fabrication of
      organic field-effect transistors (OFETs). Under optimized conditions, the field
      effect mobility (MUFET) of the EHD-jet printed OFETs was 5 times higher than the
      highest MUFET observed in the spin-coated OFETs, and this improvement was
      achieved without the use of complex surface templating or additional pre- or post
      deposition processing. As the chain alignment can be affected by the surface
      energy of the dielectric layer in EHD-jet printed OFETs, dielectric layers with
      varying wettability were examined. Near-edge X-ray absorption fine structure
      measurements were performed to compare the amorphous chain alignment in OFET
      active layers prepared by EHD-jet printing and spin coating.

PMID- 29058868
TI  - Detection of Dithiocarbamate Pesticides with a Spongelike Surface-Enhanced Raman
      Scattering Substrate Made of Reduced Graphene Oxide-Wrapped Silver Nanocubes.
AB  - Dithiocarbamate (DTC) pesticides are widely used for fruits, vegetables, and
      mature crops to control fungal diseases. Their residues in food could pose a
      threat to human health. Therefore, a surface-enhanced Raman scattering-based
      (SERS-based) sensor is developed to detect DTC pesticides because SERS can
      provide the characteristic spectrum of pesticides and avoid the use of a
      molecular recognition probe in the sensor. For the acquisition of high
      sensitivity, good anti-interference ability, and robustness of the SERS sensor, a
      silver nanocube-reduced graphene oxide (AgNC-rGO) sponge is devised. In the AgNC
      rGO sponge, the rGO sheets form a porous scaffold that physically holds the
      AgNCs, which create narrow gaps between the neighboring AgNCs, leading to the
      formation of "hot spots" for SERS-signal amplification. When DTC pesticides
      coexist with aromatic pesticides in a sample matrix, the AgNC-rGO sponge can
      selectively detect DTC pesticides because of the preferential adsorption of DTC
      pesticides on the Ag surface and aromatic pesticides on the rGO surface, which
      can effectively eliminate the interference of the SERS signals of aromatic
      pesticides, and facilitate the qualitative and quantitative analysis of DTC
      pesticides. The AgNC-rGO sponge shows great potential as a SERS substrate for
      selective detection of DTC pesticides.

PMID- 29058869
TI  - Robust 2D Room-Temperature Dilute Ferrimagnetism Enhancement in Freestanding
      Ammoniated Atom-Thin [0001] h-BN Nanoplates.
AB  - The author reports an anthracene vapor-assisted transport growth (~4.8% in yield)
      of freestanding atomically thin pristine two-dimensional (2D) hexagonal boron
      nitride (h-BN) nanoplates directly from bulk powders. A room-temperature dilute
      magnetism was first observed in the pyrolytic 2D [0001] h-BN nanoplates, which is
      attributed to the missing N atom numbers (NN) or existence of a nitrogen-vacancy
      (Nv) with volume fraction ~1.46%. Upon the postannealing in ammonia, the
      unsupported ammoniated 2D h-BN nanoplates showed an enhanced robust
      ferrimagnetism with the effective magnetic moment as high as 0.024 MUB/per N, and
      Neel temperature at 174.9 K. At 295 K, a symmetric electron paramagnetic
      resonance peak signal was experimentally measured at g ~ 2.1267, revealing the
      presence of an unpaired electron trapped at a B atom site in B-rich h-BN. As a
      promising 2D dilute magnetic semiconductor candidate, our finding favors the
      ammoniated atom-thin h-BN nanoplate for realization of spintronic nanodevices
      operating at room temperature.

PMID- 29058870
TI  - Using a Specific RNA-Protein Interaction To Quench the Fluorescent RNA Spinach.
AB  - RNAs are involved in interaction networks with other biomolecules and are crucial
      for proper cell function. Yet their biochemical analysis remains challenging. For
      Forster Resonance Energy Transfer (FRET), a common tool to study such interaction
      networks, two interacting molecules have to be fluorescently labeled. "Spinach"
      is a genetically encodable RNA aptamer that starts to fluoresce upon binding of
      an organic molecule. Therefore, it is a biological fluorophore tag for RNAs.
      However, spinach has never been used in a FRET assembly before. Here, we describe
      how spinach is quenched when close to acceptors. We used RNA-DNA hybridization to
      bring quenchers or red organic dyes in close proximity to spinach. Furthermore,
      we investigate RNA-protein interactions quantitatively on the example of
      Pseudomonas aeruginosa phage coat protein 7 (PP7) and its interacting pp7-RNA. We
      utilize spinach quenching as a fully genetically encodable system even under
      lysate conditions. Therefore, this work represents a direct method to analyze RNA
      protein interactions by quenching the spinach aptamer.

PMID- 29058871
TI  - Small-Molecule Organic Photovoltaic Modules Fabricated via Halogen-Free Solvent
      System with Roll-to-Roll Compatible Scalable Printing Method.
AB  - For the first time, the photovoltaic modules composed of small molecule were
      successfully fabricated by using roll-to-roll compatible printing techniques. In
      this study, blend films of small molecules, BTR and PC71BM were slot-die coated
      using a halogen-free solvent system. As a result, high efficiencies of 7.46% and
      6.56% were achieved from time-consuming solvent vapor annealing (SVA) treatment
      and roll-to-roll compatible solvent additive approaches, respectively. After
      successful verification of our roll-to-roll compatible method on small-area
      devices, we further fabricated large-area photovoltaic modules with a total
      active area of 10 cm2, achieving a power conversion efficiency (PCE) of 4.83%.
      This demonstration of large-area photovoltaic modules through roll-to-roll
      compatible printing methods, even based on a halogen-free solvent, suggests the
      great potential for the industrial-scale production of organic solar cells
      (OSCs).

PMID- 29058872
TI  - Bile Acid Recognition by Mouse Ileal Bile Acid Binding Protein.
AB  - Ileal bile acid binding protein (I-BABP, gene name FABP6) is a component of the
      bile acid recycling system, expressed in the ileal enterocyte. The physiological
      role of I-BABP has been hypothesized to be either an intracellular buffering
      agent to protect against excess intracellular bile acids or separately as a
      modulator of bile acid controlled transcription. We investigated mouse I-BABP (mI
      BABP) to understand the function of this protein family. Here, we studied
      energetics and site selectivity of binding with physiological bile acids using a
      combination of isothermal calorimetric analysis and NMR spectroscopy. We found
      that the most abundant bile acid in the mouse (beta-muricholic acid) binds with
      weak affinity individually and in combination with other bile acids. Further
      analysis showed that mI-BABP like human I-BABP (hI-BABP) specifically recognizes
      the conjugated form of cholic acid:chenodeoxycholic acid (CA:CDCA) in a site
      selective manner, displaying the highest affinity of any bile acid combination
      tested. These results indicate that I-BABP specifically recognizes the ligand
      combination of CDCA and CA, even in a species such as the mouse where CDCA only
      represents a trace component of the physiological pool. Specific and conserved
      recognition of the CDCA and CA ligand combination suggests that I-BABP may play a
      critical role in the regulation of bile acid signaling in addition to its
      proposed role as a buffering agent.

PMID- 29058874
TI  - Multibranched Gold Nanoparticles with Intrinsic LAT-1 Targeting Capabilities for
      Selective Photothermal Therapy of Breast Cancer.
AB  - Because of the critical role of the large neutral amino acid transporter-1 (LAT
      1) in promoting tumor growth and proliferation, it is fast emerging as a highly
      attractive biomarker for the imaging and treatment of human malignancies,
      including breast cancer. While multibranched gold nanoparticles (AuNPs) have
      emerged as a promising modality in the photothermal therapy (PTT) of cancers,
      some of the key challenges limiting their clinical translation lie in the need to
      develop reproducible and cost-effective synthetic methods as well as the
      selective accumulation of sufficient AuNPs at tumor sites. In this study, we
      report a simple and direct seed-mediated synthesis of monodispersed multibranched
      AuNPs using the catechol-containing LAT-1 ligands, L- and D-dopa, to confer
      active cancer targeting. This route obviates the need for additional conjugation
      with targeting moieties such as peptides or antibodies. Nanoflower-like AuNPs
      (AuNF) with diameters of approximately 46, 70, and 90 nm were obtained and were
      found to possess excellent colloidal stability and biocompatibility. A
      significantly higher intracellular accumulation of the L- and D-dopa
      functionalized AuNFs was observed in a panel of breast cancer cell lines (MCF-7,
      MDA-MB-231, MDA-MB-468, and MDA-MB-453) when compared to the nontargeting control
      AuNFs synthesized with dopamine and 4-ethylcatechol. Importantly, no significant
      difference in uptake between the targeting and nontargeting AuNFs was observed in
      a non-tumorigenic MCF-10A breast epithelial cell line, hence demonstrating tumor
      selectivity. For PTT of breast cancer, Ag+ was introduced during synthesis to
      obtain L-dopa functionalized nanourchin-like AuNPs (AuNUs) with strong near
      infrared (NIR) absorbance. The L-dopa functionalized AuNUs mediated selective
      photothermal ablation of the triple negative MDA-MB-231 breast cancer cell line
      and sensitized the cells to the anticancer drugs cisplatin and docetaxel. This
      work brings forward an effective strategy for the facile preparation of cancer
      targeting multibranched AuNPs with potential for the in vivo PTT of breast
      cancer.

PMID- 29058873
TI  - Radiation-Induced Damage and Recovery of Ultra-Nanocrystalline Diamond: Toward
      Applications in Harsh Environments.
AB  - Ultra-nanocrystalline diamond (UNCD) is increasingly being used in the
      fabrication of devices and coatings due to its excellent tribological properties,
      corrosion resistance, and biocompatibility. Here, we study its response to
      irradiation with kiloelectronvolt electrons as a controlled model for extreme
      ionizing environments. Real time Raman spectroscopy reveals that the radiation
      damage mechanism entails dehydrogenation of UNCD grain boundaries, and we show
      that the damage can be recovered by annealing at 883 K. Our results have
      significant practical implications for the implementation of UNCD in extreme
      environment applications, and indicate that the films can be used as radiation
      sensors.

PMID- 29058875
TI  - Large Scale Mutational and Kinetic Analysis of a Self-Hydrolyzing Deoxyribozyme.
AB  - Deoxyribozymes are catalytic DNA sequences whose atomic structures are generally
      difficult to elucidate. Mutational analysis remains a principal approach for
      understanding and engineering deoxyribozymes with diverse catalytic activities.
      However, laborious preparation and biochemical characterization of individual
      sequences severely limit the number of mutants that can be studied biochemically.
      Here, we applied deep sequencing to directly measure the activities of self
      hydrolyzing deoxyribozyme sequences in high throughput. First, all single and
      double mutants within the 15-base catalytic core of the deoxyribozyme I-R3 were
      assayed to unambiguously determine the tolerated and untolerated mutations at
      each position. Subsequently, 4096 deoxyribozyme variants with tolerated base
      substitutions at seven positions were kinetically assayed in parallel. We
      identified 533 active mutants whose first-order rate constants and activation
      energies were determined. The results indicate an isolated and narrow peak in the
      deoxyribozyme sequence space and provide a quantitative view of the effects of
      multiple mutations on the deoxyribozyme activity for the first time.

PMID- 29058876
TI  - Synthetic Xylosides: Probing the Glycosaminoglycan Biosynthetic Machinery for
      Biomedical Applications.
AB  - Glycosaminoglycans (GAGs) are polysaccharides ubiquitously found on cell surfaces
      and in the extracellular matrix (ECM). They regulate numerous cellular signaling
      events involved in many developmental and pathophysiological processes. GAGs are
      composed of complex sequences of repeating disaccharide units, each of which can
      carry many different modifications. The tremendous structural variations account
      for their ability to bind many proteins and thus, for their numerous functions.
      Although the sequence of GAG biosynthetic events and the enzymes involved mostly
      were deduced a decade ago, the emergence of tissue or cell specific GAGs from a
      nontemplate driven process remains an enigma. Current knowledge favors the
      hypothesis that macromolecular assemblies of GAG biosynthetic enzymes termed
      "GAGOSOMEs" coordinate polymerization and fine structural modifications in the
      Golgi apparatus. Distinct GAG structures arise from the differential channeling
      of substrates through the Golgi apparatus to various GAGOSOMEs. As GAGs perform
      multiple regulatory roles, it is of great interest to develop molecular
      strategies to selectively interfere with GAG biosynthesis for therapeutic
      applications. In this Account, we assess our present knowledge on GAG
      biosynthesis, the manipulation of GAG biosynthesis using synthetic xylosides, and
      the unrealized potential of these xylosides in various biomedical applications.
      Synthetic xylosides are small molecules consisting of a xylose attached to an
      aglycone group, and they compete with endogenous proteins for precursors and
      biosynthetic enzymes to assemble GAGs. This competition reduces endogenous
      proteoglycan-bound GAGs while increasing xyloside-bound free GAGs, mostly
      chondroitin sulfate (CS) and less heparan sulfate (HS), resulting in a variety of
      biological consequences. To date, hundreds of xylosides have been published and
      the importance of the aglycone group in determining the structure of the primed
      GAG chains is well established. However, the structure-activity relationship has
      long been cryptic. Nonetheless, xylosides have been designed to increase HS
      priming, modified to inhibit endogenous GAG production without priming, and
      engineered to be more biologically relevant. Synthetic xylosides hold great
      promise in many biomedical applications and as therapeutics. They are small,
      orally bioavailable, easily excreted, and utilize the host cell biosynthetic
      machinery to assemble GAGs that are likely nonimmunogenic. Various xylosides have
      been shown, in different biological systems, to have anticoagulant effects,
      selectively kill tumor cells, abrogate angiogenic and metastatic pathways,
      promote angiogenesis and neuronal growth, and affect embryonic development.
      However, most of these studies utilized the commercially available one or two
      beta-D-xylosides and focused on the impact of endogenous proteoglycan-bound GAG
      inhibition on biological activity. Nevertheless, the manipulation of cell
      behavior as a result of stabilizing growth factor signaling with xyloside-primed
      GAGs is also reckonable but underexplored. Recent advances in the use of
      molecular modeling and docking simulations to understand the structure-activity
      relationships of xylosides have opened up the possibility of a more rational
      aglycone design to achieve a desirable biological outcome through selective
      priming and inhibitory activities. We envision these advances will encourage more
      researchers to explore these fascinating xylosides, harness the GAG biosynthetic
      machinery for a wider range of biomedical applications, and accelerate the
      successful transition of xyloside-based therapeutics from bench to bedside.

PMID- 29058877
TI  - Overcoming Catalyst Residue Inhibition of the Functionalization of Single-Walled
      Carbon Nanotubes via the Billups-Birch Reduction.
AB  - The Billups-Birch Reduction chemistry has been shown to functionalize single
      walled carbon nanotubes (SWCNTs) without damaging the sidewalls, but has
      challenges in scalability. Currently published work uses a large mole ratio of Li
      to carbon atoms in the SWCNT (Li:C) to account for lithium amide formation,
      however this increases the cost and hazard of the reaction. We report here the
      systematic understanding of the effect of various parameters on the extent of
      functionalization using resonant Raman spectroscopy. Addition of 1-iodododecane
      yielded alkyl-functionalized SWCNTs, which were isolated by solvent extraction
      and evaporation, and purified by a hydrocarbon wash. The presence of SWCNT growth
      catalyst residue (Fe) was shown to have a strong adverse effect on SWCNT
      functionalization. Chlorination-based SWCNT purification reduced the amount of
      residual Fe, and achieve a maximum ID/IG ratio using a Li:C ratio of 6:1 in a
      reaction time of 30 min. This result is consistent with published literature
      requiring 20-fold mole equivalents of Li per mole SWCNT with a reaction time of
      over 12 h. This new understanding of the factors influencing the
      functionalization chemistry will help cut down material and process costs, and
      also increase the selectivity of the reaction toward the desired product.

PMID- 29058878
TI  - Influence of Porosity and Pore-Size Distribution in Ti6Al4 V Foam on
      Physicomechanical Properties, Osteogenesis, and Quantitative Validation of Bone
      Ingrowth by Micro-Computed Tomography.
AB  - Cementless fixation for orthopedic implants aims to obviate challenges associated
      with bone cement, providing long-term stability of bone prostheses after
      implantation. The application of porous titanium and its alloy-based implants is
      emerging for load-bearing applications due to their high specific strength, low
      stiffness, corrosion resistance, and superior osteoconductivity. In this study,
      coagulant-assisted foaming was utilized for the fabrication of porous Ti6Al4 V
      using egg-white foam. Samples with three different porosities of 68.3%, 75.4%,
      and 83.1% and average pore sizes of 92, 178, and 297 MUm, respectively, were
      prepared and subsequently characterized for mechanical properties, osteogenesis,
      and tissue ingrowth. A microstructure-mechanical properties relationship study
      revealed that an increase of porosity from 68.3 to 83.1% increased the average
      pore size from 92 to 297 MUm with the subsequent reduction of compresive strength
      by 85% and modulus by 90%. Samples with 75.4% porosity and a 178 MUm average pore
      size produced signifcant osteogenic effects on human mesenchymal stem cells,
      which was further supported by immunocytochemistry and real-time polymerase chain
      reaction data. Quantitative assessment of bone ingrowth by micro-computed
      tomography revealed that there was an approximately 52% higher bone formation and
      more than 90% higher bone penetration at the center of femoral defects in rabbit
      when implanted with Ti6Al4 V foam (75.4% porosity) compared to the empty defects
      after 12 weeks. Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining
      along with energy-dispersive X-ray mapping on the sections obtained from the
      retrieved bone samples support bone ingrowth into the implanted region.

PMID- 29058879
TI  - Critical Overview of the Use of Ru(II) Polypyridyl Complexes as Photosensitizers
      in One-Photon and Two-Photon Photodynamic Therapy.
AB  - Photodynamic Therapy (PDT) is an emerging technique to treat certain types of
      cancer, bacterial, fungal, and viral infections, and skin diseases. In past
      years, different research groups developed new ruthenium-containing
      photosensitizers (PSs) with tuned photophysical and biological properties to
      better fit the requirements of PDT. In this Account, we report and discuss the
      latest results in this research area, emphasizing particularly our own research.
      For example, inspired by the DNA intercalating complex [Ru(bpy)2(dppz)]2+ (bpy =
      2,2'-bipyridine; dppz = (dipyrido[3,2-a:2',3'-c]phenazine), a series of ruthenium
      complexes bearing differently functionalized dppz ligands were synthesized to
      target DNA. The introduction of the substituents on the dppz ligand did not
      reduce much the affinity of the complexes to DNA but highly affected their
      cellular uptake. The most effective complex in this series, [Ru(bpy)2(dppz-7
      OMe)]2+, showed IC50 values in the low micromolar range against several types of
      cancer cells upon light irradiation and, importantly, a high phototoxic index
      (PI) of >150. This value is comparable to or even better than several PSs used in
      clinics under comparable experimental conditions. This compound was found to
      localize in the nucleus and to induce DNA damage in HeLa cells upon light
      irradiation. Interestingly, cells in the mitotic phase were found to be more
      affected and to have a different mechanism of cell death (apoptosis) upon light
      irradiation than those in the interphase (paraptosis). To take advantage of that,
      the PS was combined with a cell cycle inhibitor to synchronize cells in the
      mitotic phase, further improving the phototoxicity by a factor of 3.6. In
      addition, our group recently demonstrated that [Ru(bphen)2(benzene-1,2
      dislufinate)] (bphen = 4,7-diphenyl-1,10-phenanthroline) localizes in
      mitochondria and has an IC50 value of 0.62 MUM with a PI of over 80 in HeLa cells
      upon light irradiation at 420 nm. Interestingly, this complex was also found to
      efficiently kill Gram-positive Staphylococcus aureus under light irradiation.
      Antimicrobial PDT (aPDT) is another field of research where Ru(II) polypyridyl
      complexes can play an interesting role to fight antibiotics resistance.
      [Ru(dqpCO2Me)(ptpy)]2+ (dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8
      yl)pyridine), ptpy = 4'-phenyl-2,2':6',2"-terpyridine) is additionally efficient
      against Gram-negative Escherichia coli. The efficacy of positively charged Ru(II)
      PSs is related to their affinity to the negatively charged membrane of Gram
      negative bacteria. A drawback of many Ru(II) polypyridyl PSs is their low
      absorption in the biological optical window (600-900 nm) where light penetration
      depth into tissue is the highest. The lowest energy transition in the UV/Vis
      spectra of Ru(II) polypyridyl complexes is usually a metal-to-ligand charge
      transfer band. To shift the absorption into this range, tuning of the ligand
      system, for example, by extending pi-systems, has been described in the
      literature. Another approach to make excitation in the optical biological window
      possible is Two-Photon Absorption (2PA). High photon density is needed and
      usually confocal laser beams are used for excitation. In collaboration with the
      Chao group, a series of homoleptic Ru(II) complexes bearing tertiary alkyl
      ammonium substituted bipyridine ligands with two photon cross sections between
      185 and 250 GM at around 800 nm was tested in vitro. They showed IC50 values in
      the micromolar range and PIs between 103 and 313. The highly positive-charged
      complexes were found to enter the cell via endocytosis and to target lysosomes.
      Studies on 3D tumor cell spheroids, a model closer to real tumors than commonly
      used 2D cell monolayers, were also performed. It could be demonstrated that 2P
      PDT treatment with 800 nm laser irradiation was significantly more effective than
      that with 450 nm laser irradiation.

PMID- 29058881
TI  - Chiral Pincer Carbodicarbene Ligands for Enantioselective Rhodium-Catalyzed
      Hydroarylation of Terminal and Internal 1,3-Dienes with Indoles.
AB  - Catalytic enantioselective addition of N-heteroarenes to terminal and internal
      1,3-dienes is reported. Reactions are promoted by 5 mol % of Rh catalyst
      supported by a new chiral pincer carbodicarbene ligand that delivers allylic
      substituted arenes in up to 95% yield and up to 98:2 er. Mechanistic and X-ray
      evidence is presented that supports that the reaction proceeds via a Rh(III)-eta3
      allyl.

PMID- 29058880
TI  - Hydroxyapatite as a Vehicle for the Selective Effect of Superparamagnetic Iron
      Oxide Nanoparticles against Human Glioblastoma Cells.
AB  - Despite the early promises of magnetic hyperthermia (MH) as a method for treating
      cancer, it has been stagnating in the past decade. Some of the reasons for the
      low effectiveness of superparamagnetic nanoparticles (SPIONs) in MH treatments
      include (a) low uptake in cancer cells; (b) generation of reactive oxygen species
      that cause harm to the healthy cells; (c) undeveloped targeting potential; and
      (d) lack of temperature sensitivity between cancer cells and healthy cells. Here
      we show that healthy cells, including human mesenchymal stem cells (MSCs) and
      primary mouse kidney and lung fibroblasts, display an unfavorably increased
      uptake of SPIONs compared to human brain cancer cells (E297 and U87) and mouse
      osteosarcomas cells (K7M2). Hydroxyapatite (HAP), the mineral component of our
      bones, may offer a solution to this unfavorably selective SPION delivery. HAP
      nanoparticles are commended not only for their exceptional biocompatibility but
      also for the convenience of their use as an intracellular delivery agent. Here we
      demonstrate that dispersing SPIONs in HAP using a wet synthesis method could
      increase the uptake in cancer cells and minimize the risk to healthy cells.
      Specifically, HAP/SPION nanocomposites retain the superparamagnetic nature of
      SPIONs, increase the uptake ratio between U87 human brain cancer cells and human
      MSCs versus their SPION counterparts, reduce migration in a primary brain cancer
      spheroid model compared to the control, reduce brain cancer cell viability
      compared to the treatment with SPIONs alone, and retain the viability of healthy
      human MSCs. A functional synergy between the two components of the nanocomposites
      was established; as a result, the cancer versus healthy cell (U87/MSC)
      selectivity in terms of both the uptake and the toxicity was higher for the
      composite than for SPIONs or HAP alone, allowing it to be damaging to cancer
      cells and harmless to the healthy ones. The analysis of actin cytoskeleton order
      at the microscale revealed that healthy MSCs and primary cancer cells after the
      uptake of SPIONs display reduced and increased anisotropy in their cytoskeletal
      arrangement, respectively. In contrast, the uptake of SPION/HAP nanocomposites
      increased the cytoskeletal anisotropy of both the healthy MSCs and the primary
      cancer cells. In spite of the moderate specific magnetization of HAP/SPION
      nanohybrids, reaching 15 emu/g for the 28.6 wt % SPION-containing composite, the
      cancer cell treatment in an alternating magnetic field resulted in an intense
      hyperthermia effect that increased the temperature by ca. 1  degrees C per minute
      of exposure and reduced the cell population treated for 30 min by more than 50%,
      while leaving the control populations unharmed. These findings on nanocomposites
      of HAP and SPIONs may open a new avenue for cancer therapies that utilize MH.

PMID- 29058882
TI  - Reaction Mechanism of Low-Spin Iron(III)- and Cobalt(III)-Containing Nitrile
      Hydratases: A Quantum Mechanics Investigation.
AB  - To elucidate the catalytic mechanism of cobalt(III)-benzonitrile and iron(III)-
      pivalonitrile hydratases, we have performed at density functional level a study
      using the cluster model approach. Computations were made in a protein framework.
      Following the suggestions given in a recent work on the analogous enzyme Fe(III)
      NHase, we have explored the feasibility of a new working mechanism of examined
      enzymes. According to our results, after the formation of enzyme substrate
      complex, the reaction evolves toward product in only three steps. The first one
      is the nucleophilic attack, led by the -OH group of the alphaCys113-S-OH on the
      nitrile carbon atom, followed by the amide formation and by the enzyme restoring
      phase that our computations indicate as the most expensive step from the
      energetic point of view in both catalytic processes.

PMID- 29058883
TI  - Substituent Effect of the Bridging Ligand in the Trinuclear Ru Complexes on
      Photocatalytic Oxygenation of a Sulfide and Alkenes.
AB  - To examine the effect of tuning the electron transfer ability between
      photosensitizers and reaction centers on the activity of visible-light-driven
      catalysts, a series of trinuclear Ru photocatalysts containing two Ru(II)
      photosensitizers and a Ru(II) reaction center bridged by a substituted
      bipyrimidine was prepared. The introduction of electron-donating or electron
      withdrawing groups on the ligands was found to affect the photophysical and
      electrochemical properties of these catalysts. Density functional theory
      calculations of the mononuclear Ru complexes with nonsubstituted and substituted
      bipyrimidine ligands, which correspond to the reaction center of the trinuclear
      complexes, revealed how the electronic effect of the substituents affect the
      frontier orbital energies. For photocatalytic oxygenation of a sulfide and
      terminal alkenes, the catalyst with a 5,5'-dibromo-2,2'-bipyrimidine ligand
      showed higher activity than the catalyst with 5,5'-dimethyl-2,2'-bipyrimidine and
      nonsubstituted bipyrimidine ligands, as expected according to the electronic
      effects of these ligands. In contrast, the catalyst with the nonsubstituted
      bipyrimidine ligand showed the highest activity toward inner alkenes, which may
      be due to steric effects.

PMID- 29058884
TI  - Dye-Sensitized Hydrobromic Acid Splitting for Hydrogen Solar Fuel Production.
AB  - Hydrobromic acid (HBr) has significant potential as an inexpensive feedstock for
      hydrogen gas (H2) solar fuel production through HBr splitting. Mesoporous thin
      films of anatase TiO2 or SnO2/TiO2 core-shell nanoparticles were sensitized to
      visible light with a new RuII polypyridyl complex that served as a photocatalyst
      for bromide oxidation. These thin films were tested as photoelectrodes in dye
      sensitized photoelectrosynthesis cells. In 1 N HBr (aq), the photocatalyst
      undergoes excited-state electron injection and light-driven Br- oxidation. The
      injected electrons induce proton reduction at a Pt electrode. Under 100 mW cm-2
      white-light illumination, sustained photocurrents of 1.5 mA cm-2 were measured
      under an applied bias. Faradaic efficiencies of 71 +/- 5% for Br- oxidation and
      94 +/- 2% for H2 production were measured. A 12 MUmol h-1 sustained rate of H2
      production was maintained during illumination. The results demonstrate a
      molecular approach to HBr splitting with a visible light absorbing complex
      capable of aqueous Br- oxidation and excited-state electron injection.

PMID- 29058885
TI  - A Deep Insight into the Photoluminescence Properties of Schiff Base CdII and ZnII
      Complexes.
AB  - A tridentate N,N,O donor ligand 2,4-dichloro-2-[(2-piperazine-4-yl-ethylimino)
      methyl]-phenol (HL) was designed, and eight new ZnII and CdII complexes, namely,
      [Zn(LH)(SCN)2] (1), [Zn(LH)(N3)2] (2), [Zn(LH)(NO2)2] (3), [Zn(LH)(dca)(OAc)]
      (4), [Cd2(LH)2(SCN)4] (5), [Cd(LH)(N3)2] (6), [Cd(LH)(NO2)2] (7), and
      [Cd(LH)(dca)(OAc)] (8) [where dca = dicyanamide anion] were synthesized. Five of
      them (1, 2, 4, 5, 7) were structurally characterized through single-crystal X-ray
      diffraction analysis. H-Bonding interactions are found to be the major
      stabilizing factor for crystallization in the solid state. Experimental and
      computational studies were performed in cooperation to provide a rationalization
      of the photoluminescence properties of those complexes. The quantum yields are
      anion-dependent, with enhanced efficiencies in the following order: LH < Cd
      SCN(5) < Cd-dca(8) < Cd-N3(6) < Cd-NO2(7) < Zn-dca(4) < Zn-N3(2) < ZnNO2(3) <
      ZnSCN(1). By using quantum chemical calculations we rationalized the above
      trends. Moreover, the diverse lifetimes observed for those eight complexes were
      also quantitatively explained by considering the subtle competition between
      different photo-deactivation pathways.

PMID- 29058886
TI  - Nanoscale Structure Dynamics within Electrocatalytic Materials.
AB  - Electrochemical interfaces used for sensing, (electro)catalysis, and energy
      storage are usually nanostructured to expose particular surface sites, but
      probing the intrinsic activity of these sites is often beyond current
      experimental capability. Herein, it is demonstrated how a simple meniscus imaging
      probe of just 30 nm in size can be deployed for direct electrochemical and
      topographical imaging of electrocatalytic materials at the nanoscale. Spatially
      resolved topographical and electrochemical data are collected synchronously to
      create topographical images in which step-height features as small as 2 nm are
      easily resolved and potential-resolved electrochemical activity movies composed
      of hundreds of images are obtained in a matter of minutes. The technique has been
      benchmarked by investigating the hydrogen evolution reaction on molybdenum
      disulfide, where it is shown that the basal plane possesses uniform activity,
      while surface defects (i.e., few to multilayer step edges) give rise to a
      morphology-dependent (i.e., height-dependent) enhancement in catalytic activity.
      The technique was then used to investigate the electro-oxidation of hydrazine at
      the surface of electrodeposited Au nanoparticles (AuNPs) supported on glassy
      carbon, where subnanoentity (i.e., sub-AuNP) reactivity mapping has been
      demonstrated. We show, for the first time, that electrochemical reaction rates
      vary significantly across an individual AuNP surface and that these single
      entities cannot be considered as uniformly active. The work herein provides a
      road map for future studies in electrochemical science, in which the activity of
      nanostructured materials can be viewed as quantitative movies, readily obtained,
      to reveal active sites directly and unambiguously.

PMID- 29058887
TI  - Noneffervescent Method for Catalysis-Based Palladium Detection with Color or
      Fluorescence.
AB  - Palladium is a highly valuable metal in automobile, chemical, and pharmaceutical
      industries. The metal is generally quantified by atomic absorption spectrometry
      or inductively coupled plasma mass spectrometry. These techniques are tedious and
      require expensive instruments that are operated mostly off site. As cost
      effective and user-friendly alternatives to these techniques, we previously
      reported two practical fluorometric or colorimetric methods to quantify
      palladium. Both methods rely on the use of NaBH4, which cannot be stored in
      solution for more than 10 days. Commercially available solutions of NaBH4 are
      partially or fully degraded to di- or triborohydride species and cannot be used
      for palladium(0)-catalyzed allylic C-O bond cleavage for quantification purposes.
      Here, we report a new method that replaces NaBH4 with NH2NH2 for the palladium
      catalyzed deallylation of fluorogenic and colorimetric chemodosimeter resorufin
      allyl ether. This method is slower but as sensitive as the most recent method
      from our laboratory. The method is selective for palladium and depends on the
      presence of tri(2-furyl)phosphine as a palladium ligand and NH2NH2 as a palladium
      reducing reagent.

PMID- 29058888
TI  - Directional Growth of Ultralong CsPbBr3 Perovskite Nanowires for High-Performance
      Photodetectors.
AB  - Directional growth of ultralong nanowires (NWs) is significant for practical
      application of large-scale optoelectronic integration. Here, we demonstrate the
      controlled growth of in-plane directional perovskite CsPbBr3 NWs, induced by
      graphoepitaxial effect on annealed M-plane sapphire substrates. The wires have a
      diameter of several hundred nanometers, with lengths up to several millimeters.
      Microstructure characterization shows that CsPbBr3 NWs are high-quality single
      crystals, with smooth surfaces and well-defined cross section. The NWs have very
      strong band-edge photoluminescence (PL) with a long PL lifetime of ~25 ns and can
      realize high-quality optical waveguides. Photodetectors constructed on these
      individual NWs exhibit excellent photoresponse with an ultrahigh responsivity of
      4400 A/W and a very fast response speed of 252 MUs. This work presents an
      important step toward scalable growth of high-quality perovskite NWs, which will
      provide promising opportunities in constructing integrated nanophotonic and
      optoelectronic systems.

PMID- 29058889
TI  - Remote Cooperative Group Strategy Enables Ligands for Accelerative Asymmetric
      Gold Catalysis.
AB  - An accelerative asymmetric gold catalysis is achieved for the first time via
      chiral ligand metal cooperation. An asymmetrically positioned remote amide group
      in the designed chiral binaphthyl-based ligand plays the essential role of a
      general base catalyst and selectively accelerates the cyclizations of 4-allen-1
      ols into one prochiral allene face. The reactions are mostly highly
      enantioselective with achiral substrates, and due to the accelerated nature of
      the catalysis catalyst loadings as low as 100 ppm are allowed. With a pre
      existing chiral center at any of the backbone sp3-carbons, the reaction remained
      highly efficient and most importantly maintained excellent allene facial
      selectivities regardless of the substrate stereochemistry. By using different
      combinations of ligand and substrate enantiomers, it is now possible to access
      all four stereoisomers of versatile 2-vinyltetrahydrofurans with exceedingly high
      selectivity. The underpinning design of this chemistry reveals a novel and
      conceptually distinctive strategy to tackle challenging asymmetric gold
      catalysis, which to date has relied on decelerative asymmetric steric hindrance
      approaches.

PMID- 29058890
TI  - Direct Observation on Reaction Intermediates and the Role of Bicarbonate Anions
      in CO2 Electrochemical Reduction Reaction on Cu Surfaces.
AB  - Cu is the only monometallic catalyst that produces a large amount of hydrocarbon
      fuels during the CO2 electrochemical reduction reaction (CO2RR). However, the
      CO2RR mechanism and the impact of electrolyte are unclear. In this communication,
      two important issues regarding the CO2RR on Cu surfaces are studied: (1) the
      direct observation on reaction intermediates and (2) the role of the electrolyte
      (KHCO3) in the reaction. Surface-enhanced infrared absorption spectroscopy allows
      direct observation of several reaction intermediates that have never been
      detected before, except for the commonly detected CO. Another important finding
      is that CO2 molecules are mediated to the Cu surface via their equilibrium with
      bicarbonate anions instead of direct adsorption from the solution. These results
      shed light on the full understanding of the CO2RR on Cu surfaces and developing
      more advanced catalysts.

PMID- 29058891
TI  - Enzyme Architecture: Erection of Active Orotidine 5'-Monophosphate Decarboxylase
      by Substrate-Induced Conformational Changes.
AB  - Orotidine 5'-monophosphate decarboxylase (OMPDC) catalyzes the decarboxylation of
      5-fluoroorotate (FO) with kcat/Km = 1.4 * 10-7 M-1 s-1. Combining this and
      related kinetic parameters shows that the 31 kcal/mol stabilization of the
      transition state for decarboxylation of OMP provided by OMPDC represents the sum
      of 11.8 and 10.6 kcal/mol stabilization by the substrate phosphodianion and the
      ribosyl ring, respectively, and an 8.6 kcal/mol stabilization from the orotate
      ring. The transition state for OMPDC-catalyzed decarboxylation of FO is
      stabilized by 5.2, 7.2, and 9.0 kcal/mol, respectively, by 1.0 M phosphite
      dianion, d-glycerol 3-phosphate and d-erythritol 4-phosphate. The stabilization
      is due to the utilization of binding interactions of the substrate fragments to
      drive an enzyme conformational change, which locks the orotate ring of the whole
      substrate, or the substrate pieces in a caged complex. We propose that enzyme
      activation is a possible, and perhaps probable, consequence of any substrate
      induced enzyme conformational change.

PMID- 29058892
TI  - Efficient and Rapid Mechanochemical Assembly of Platinum(II) Squares for Guanine
      Quadruplex Targeting.
AB  - We present a rapid and efficient method to generate a family of platinum
      supramolecular square complexes, including previously inaccessible targets,
      through the use of ball milling mechanochemistry. This one-pot, two-step process
      occurs in minutes and enables the synthesis of the squares
      [Pt4(en)4(N?N)4][CF3SO3]8 (en= ethylenediamine, N?N = 4,4'-bipyridine
      derivatives) from commercially available precursor K2PtCl4 in good to excellent
      yields. In contrast, solution-based assembly requires heating the reagents for
      weeks and gives lower yields. Mechanistic investigations into this remarkable
      rate acceleration revealed that solution-based assembly (refluxing for days)
      results in the formation of large oligomeric side-products that are difficult to
      break down into the desired squares. On the other hand, ball milling in the solid
      state is rapid and appears to involve smaller intermediates. We examined the
      binding of the new supramolecular squares to guanine quadruplexes, including
      oncogene and telomere-associated DNA and RNA sequences. Sub-micromolar binding
      affinities were obtained by fluorescence displacement assays (FID) and isothermal
      titration calorimetry (ITC), with binding preference to telomere RNA (TERRA)
      sequences. ITC showed a 1:1 binding stoichiometry of the metallosquare to TERRA,
      while the stoichiometry was more complex for telomeric quadruplex DNA and a
      double-stranded DNA control.

PMID- 29058893
TI  - Detection of Amphipathic Viral Peptide on Screen-Printed Electrodes by Liposome
      Rupture Impact Voltammetry.
AB  - Detection of infectious viruses and disease biomarkers is of utmost importance in
      clinical screening for effective identification and treatment of diseases. We
      demonstrate here the use of liposome rupture impact voltammetry for the
      qualitative detection of model amphipathic viral peptide on a screen-printed
      electrode. This novel, proof-of-concept method was proposed for the quick and
      reliable detection of viruses by nonfaradaic liposome rupture impact voltammetry
      with the aid of 1,2-dioleoyl-sn-glycero-3-phosphocholine liposomes. This provides
      an avenue for the development of future on-site, point-of-care detection devices
      for medical and biological applications.

PMID- 29058894
TI  - Nucleophilic Addition of Ketones To Acetylenes and Allenes: A Quantum-Chemical
      Insight.
AB  - A CBS-Q//B3 based study has been carried out to elucidate the mechanism of the
      KOH/DMSO superbase catalyzed ketones nucleophilic addition to alkyl propargyl and
      alkyl allenyl ethers yielding, along with (Z)-monoadducts, up to 26% of
      unexpected (E)-diadducts. The impact of different substrates (alkynes versus
      allenes) on the reaction mechanism has been discussed in detail. Along with the
      model reaction of acetone addition to propyne and allene, the addition of acetone
      and acetophenone to methyl propargyl and methyl allenyl ethers is considered. The
      limiting reaction stage of the starting ketone carbanion addition to propargyl
      and allenyl systems occurs with activation energies typical for vinylation of
      ketones. In contrast, the addition of intermediate alpha-carbanions to the
      terminal position of methyl allenyl ether is associated with unusually low
      activation barriers. The results obtained explain the composition of the reaction
      products and indicate the participation of mainly the allene form in the
      reaction.

PMID- 29058895
TI  - Metal-Ion- and Hydrogen-Bond-Mediated Interstellar Prebiotic Chemistry: The First
      Step in the Formose Reaction.
AB  - The formose reaction, which offers a feasible chemical pathway for the prebiotic
      synthesis of sugars, is a well-studied reaction for over two hundred and 50
      years. Yet huge knowledge gaps exist even in the very first step of the formose
      reaction. In this work, we provide a new and otherwise unintuitive reaction
      pathway for the gas-phase conversion of formaldehyde to glycolaldehyde (the first
      step in the formose reaction) occurring in the interstellar medium (ISM).
      Employing electronic structure calculations (CCSD(T) and DFT methods), we
      exhaustively probe the role of various metal ions and small molecules detected in
      the ISM to propose a new mechanism wherein metal-oxygen interactions and hydrogen
      bonds cooperatively facilitate an otherwise implausible chemical reaction. The
      reactions involving Mg2+ are throughout found to be barrierless, and those
      featuring Al+ ions are noted to only have a small barrier. The proton affinities
      of the small molecules, metal-oxygen interactions, and the extent of C-C-bond
      formation are found to be the significant factors that influence the barrier
      heights. The mechanism is also shown to be consistent with well-known
      experimental details in the terrestrial formose reaction (which could, however,
      proceed through a different mechanism). Future experimental and theoretical scope
      arising out of this paper are subsequently discussed.

PMID- 29058896
TI  - Comprehensive Lipidome-Wide Profiling Reveals Dynamic Changes of Tea Lipids
      during Manufacturing Process of Black Tea.
AB  - As important biomolecules in Camellia sinensis L., lipids undergo substantial
      changes during black tea manufacture, which is considered to contribute to tea
      sensory quality. However, limited by analytical capacity, detailed lipid
      composition and its dynamic changes during black tea manufacture remain unclear.
      Herein, we performed tea lipidome profiling using high resolution liquid
      chromatography coupled to mass spectrometry (LC-MS), which allows simultaneous
      and robust analysis of 192 individual lipid species in black tea, covering 17
      (sub)classes. Furthermore, dynamic changes of tea lipids during black tea
      manufacture were investigated. Significant alterations of lipid pattern were
      revealed, involved with chlorophyll degradation, metabolic pathways of
      glycoglycerolipids, and other extraplastidial membrane lipids. To our knowledge,
      this report presented most comprehensive coverage of lipid species in black tea.
      This study provides a global and in-depth metabolic map of tea lipidome during
      black tea manufacture.

PMID- 29058897
TI  - Size-Dependent Level Alignment between Rutile and Anatase TiO2 Nanoparticles:
      Implications for Photocatalysis.
AB  - Motivated by the enormous importance of nanoscale TiO2 in a wide range of
      photocatalytic applications and the ill-understood high activity of the
      commercial nano-TiO2 photocatalysts, we provide a predictive map of how the
      anatase-rutile level alignment varies from the smallest nanoparticles (NPs) to
      the bulk. Specifically, we compute the size dependence of the energies of vacuum
      referenced electronic levels in a range of realistically structured rutile and
      anatase TiO2 NPs employing accurate all-electron density functional calculations.
      In agreement with most recent work, a staggered type II anatase level alignment
      is predicted for the bulk phases, which we further find to persist into the
      regime of large NPs. We predict that other level alignments will emerge when the
      diameter of the TiO2 NPs is reduced below ~15 nm. Our results suggest how
      experiment could test the widely debated importance of the bulk-like type II
      anatase level alignment for enhanced photoactivity of nano-TiO2.

PMID- 29058898
TI  - Reaction of CO2 with Groups 4 and 6 Transition Metal Oxide Clusters.
AB  - Density functional theory (DFT) and coupled cluster theory (CCSD(T)) were used to
      study the addition of CO2 to group 4 (MO2)n and group 6 (MO3)n (n = 1, 2, 3)
      nanoclusters. The structures and energetics arising from Lewis acid-base addition
      (physisorption) and formation of CO32- (chemisorption) of CO2 to these clusters
      were predicted. Physisorption and chemisorption of CO2 are predicted to be
      thermodynamically allowed for group 4 (MO2)n clusters, with chemisorption being
      more favored energetically. Correlations of the ligand binding energies (LBEs)
      for the group 4 clusters are made with the fluoride affinities and M-O and M?O
      bond strengths of the clusters. The LBEs for chemisorption on the Zr and Ti
      clusters are consistent with published experimental and computational studies of
      bulk solids. Physisorption LBEs for the Ti and Zr clusters are more exothermic
      than the bulk values, as the cluster models allow for better relaxation at the
      metal sites. Chemisorption is not predicted to occur with group 6 (MO3)n
      clusters, as the larger chemisorbed structures were all found to be metastable.
      CO2 is predicted to weakly physisorb to (WO3)n with physisorption correlating
      with the Lewis acidity of the metal site.

PMID- 29058899
TI  - Theoretical Investigation of Distributions of Run Lengths for Biological
      Molecular Motors.
AB  - Motor proteins, also known as biological molecular motors, are active enzymatic
      molecules that support a variety of fundamental biological processes, including
      cellular transport, cell division, and cell motility. They usually function by
      transforming chemical energy into mechanical motion, which propels them along
      linear structures such as protein filaments and nucleic acids. Recent single
      molecule experiments measured with high-precision distributions of various
      dynamic properties of molecular motors. However, it is difficult to utilize these
      observations to obtain a better description of molecular mechanisms in motor
      proteins because of the lack of corresponding theoretical methods. To fill this
      gap, we developed a new theoretical framework to describe the distributions of
      dynamic properties of biological molecular motors. It is based on the method of
      first-passage processes. To illustrate our approach, the distributions of run
      lengths of motor proteins are analyzed. It is found that these distributions
      depend on the finite length of linear tracks along which the motors move, on the
      initial position of the motor proteins along the filaments, and on the
      intermediate chemical transitions during the enzymatic cycle. The physical
      mechanisms of the observed phenomena are discussed.

PMID- 29058900
TI  - Optical and Structural Properties of ESIPT Inspired HBT-Fluorene Molecular
      Aggregates and Liquid Crystals.
AB  - In bulk materials, positional isomers not only help in understanding how slight
      difference in molecular structure alters the crystal packing and optical
      properties, but also play a key role in developing new type of materials for
      functional applications. A detailed study on the photophysical properties of
      fluorene-HBT positional isomers in solution and in the solid state providing a
      molecular level understanding of the factors which influence fluorescence
      behavior is reported. Two molecules Ia and IIa were synthesized by Suzuki
      coupling reaction and their photophysical properties were compared to positional
      isomers Ib and IIb. Crystal structure analyses and density functional theory
      (DFT) computation studies were performed to understand structure-properties
      relation and the results reveal that changing substitution pattern has a marked
      influence on their packing modes and luminescence properties. Strong noncovalent
      interactions (pi-pi) in the solid state hamper the excited state intramolecular
      proton transfer (ESIPT) process which causes fluorescence quenching in the solid
      state (Ia and IIa = Phif, 28-40%; Ib and IIb = Phif, 55-67%). Compounds show
      solvent-responsive and aggregation induced emission (AIE) properties. Bent
      structures of Ia with double and symmetric substitution of ESIPT motifs exhibit
      particularly unique condensed phase upon heating, confirmed as a nematic liquid
      crystalline phase, and this is the first report on the ESIPT and AIE active
      liquid crystalline materials with a banana-shaped molecule.

PMID- 29058901
TI  - Impact of Lattice Water on Solid-State Electron Transfer in Viologen
      Pseudopolymorphs: Modulation of Photo- and Piezochromism.
AB  - Stimuli-induced solid-state electron transfer (ET) underlies the use of viologen
      compounds as responsive materials, but unequivocal structure-property
      correlations for solid-state ET are still lacking. With different
      pseudopolymorphic solids derived from N,N'-bis(4-carboxylphenyl)viologen
      ([H2bcpV]2+), here we report a systematic study on photo- and piezochromic
      properties associated with ET. We show that the higher the water content in the
      lattice, the less sensitively the compounds respond to light and pressure. It is
      proposed that the lattice water does not act as an electron donor but serves to
      change the ET energetics through its unique polarity and hydrogen bonding
      capability. The impedimental impact of water on solid-state ET of viologen
      compounds has not yet been recognized and elucidated prior to this work. The
      study also suggests that pressure is more powerful than light in inducing ET.

PMID- 29058902
TI  - In Situ Monitoring of Chemical Reactions at a Solid-Water Interface by
      Femtosecond Acoustics.
AB  - Chemical reactions at a solid-liquid interface are of fundamental importance.
      Interfacial chemical reactions occur not only at the very interface but also in
      the subsurface area, while existing monitoring techniques either provide limited
      spatial resolution or are applicable only for the outmost atomic layer. Here,
      with the aid of the time-domain analysis with femtosecond acoustics, we
      demonstrate a subatomic-level-resolution technique to longitudinally monitor
      chemical reactions at solid-water interfaces, capable of in situ monitoring even
      the subsurface area under atmospheric conditions. Our work was proven by
      monitoring the already-known anode oxidation process occurring during
      photoelectrochemical water splitting. Furthermore, whenever the oxide layer
      thickness equals an integer  number of the effective atomic layer thickness, the
      measured acoustic echo will show higher signal-to-noise ratios with reduced
      speckle noise, indicating the quantum-like behavior of this coherent-phonon-based
      technique.

PMID- 29058903
TI  - Infrared Fingerprints of nN -> sigma*NH Hyperconjugation in Hydrazides.
AB  - An earlier study demonstrated that hyperconjugation operates in hydrazides by
      analyzing the N-H stretching mode in gas phase infrared (IR) spectroscopy, and
      then observing two very distinct bands corresponding to isolated isomers
      experiencing or not the nN -> sigma*N-H electron delocalization. The present work
      reports a chemical method to obtain insight on the hyperconjugation in hydrazide
      derivatives from solution IR spectroscopy. The analogous amides did not show a
      nuN-H red-shifted band, as the electron donor orbital in the above
      hyperconjugative interaction does not exist. In addition, the effect of electron
      withdrawing groups bonded to a nitrogen atom, namely the trifluoroacetyl and the
      methanesulfonyl groups, was analyzed on the conformational isomerism and on the
      ability to induce a stronger hyperconjugation in the resulting compounds.

PMID- 29058904
TI  - Formation of a Hydroxymethylfurfural-Cysteine Adduct and Its Absorption and
      Cytotoxicity in Caco-2 Cells.
AB  - Adducts of 5-hydroxymethylfurfural (HMF)-amino acids are formed during food
      processing and digestion; the elimination capacity of in vitro intestinal digests
      of biscuits, instant noodles, and potato crisps for HMF is 652, 727, and 540
      MUg/g, respectively. However, the safety of these adducts is unknown. In this
      study, an HMF-cysteine adduct named 1-dicysteinethioacetal-5
      hydroxymehtylfurfural (DCH), which was found to be produced in the
      gastrointestinal tract after HMF intake, was prepared to test its effect toward
      Caco-2 cells. Compared with HMF, the adduct displayed lower cytotoxicity against
      Caco-2 cells with an IC50 value of 31.26 mM versus 14.95 mM (HMF). The DCH did
      not induce cell apoptosis, whereas HMF significantly increased the apoptosis rate
      after incubation at concentrations of 16, 32, and 48 mM for 72 h. DCH showed an
      absorption rate considerably lower than that of HMF by Caco-2 cells. Lower
      absorption of DCH may result in lower toxicity compared with HMF against Caco-2
      cells. Intracellular transformation of DCH has been observed.

PMID- 29058905
TI  - Multiple Water-in-Oil-in-Water Emulsion Gels Based on Self-Assembled Saponin
      Fibrillar Network for Photosensitive Cargo Protection.
AB  - A gelled multiple water-in-oil-in-water (W1/O/W2) emulsion was successfully
      developed by the unique combination of emulsifying and gelation properties of
      natural glycyrrhizic acid (GA) nanofibrils, assembling into a fibrillar hydrogel
      network in the continuous phase. The multiple emulsion gels had relatively
      homogeneous size distribution, high yield (85.6-92.5%), and superior storage
      stability. The multilayer interfacial fibril shell and the GA fibrillar hydrogel
      in bulk can effectively protect the double emulsion droplets against
      flocculation, creaming, and coalescence, thus contributing to the multiple
      emulsion stability. Particularly, the highly viscoelastic bulk hydrogel had a
      high storage modulus, which was found to be able to strongly prevent the osmotic
      driven water diffusion from the internal water droplets to the external water
      phase. We show that these multicompartmentalized emulsion gels can be used to
      encapsulate and protect photosensitive water-soluble cargos by loading them into
      the internal water droplets. These stable multiple emulsion gels based on
      natural, sustainable saponin nanofibrils have potential applications in the food,
      pharmaceutical, and personal care industries.

PMID- 29058906
TI  - Predicting Counterion Effects Using a Gold Affinity Index and a Hydrogen Bonding
      Basicity Index.
AB  - We have developed a gold affinity index and hydrogen bonding basicity index for
      counterions and have used these indexes to forecast their reactivity in cationic
      gold catalysis.

PMID- 29058907
TI  - Doping-Driven Wettability of Two-Dimensional Materials: A Multiscale Theory.
AB  - Engineering molecular interactions at two-dimensional (2D) materials interfaces
      enables new technological opportunities in functional surfaces and molecular
      epitaxy. Understanding the wettability of 2D materials represents the crucial
      first step toward quantifying the interplay between the interfacial forces and
      electric potential of 2D materials interfaces. Here we develop the first
      theoretical framework to model the wettability of the doped 2D materials by
      properly bridging the multiscale physical phenomena at the 2D interfaces,
      including (i) the change of 2D materials surface energy (atomistic scale, several
      angstroms), (ii) the molecular reorientation of liquid molecules adjacent to the
      interface (molecular scale, 100-101 nm), and (iii) the electrical double layer
      (EDL) formed in the liquid phase (mesoscopic scales, 100-104 nm). The latter two
      effects are found to be the major mechanisms responsible for the contact angle
      change upon doping, while the surface energy change of a pure 2D material has no
      net effect on the wetting property. When the doping level is electrostatically
      tuned, we demonstrate that 2D materials with high quantum capacitances (e.g.,
      transition metal dichalcogenides, TMDCs) possess a wider range of tunability in
      the interfacial tension, under the same applied gate voltage. Furthermore,
      practical considerations such as defects and airborne contamination are also
      quantitatively discussed. Our analysis implies that the doping level can be
      another variable to modulate the wettability at 2D materials interfaces, as well
      as the molecular packing behavior on a 2D material-coated surface, essentially
      facilitating the interfacial engineering of 2D materials.

PMID- 29058908
TI  - Intracellular Fate of Nanoparticles with Polydopamine Surface Engineering and a
      Novel Strategy for Exocytosis-Inhibiting, Lysosome Impairment-Based Cancer
      Therapy.
AB  - Polydopamine (PDA) coating as a bioinspired strategy for nanoparticles (NPs) has
      been extensively applied in cancer theranostics. However, a cellular-level
      understanding of nano-biointeraction of these PDA-coated NPs (PDNPs), which
      drives the fate of them and acts as a critical step to determine their efficacy,
      still remains unknown. Herein, we utilized the representative mesoporous silica
      NPs (MSNs) to be coated with PDA and study their nano-bioactivities in cancer
      cells. HeLa cell line was utilized as a model in this study. The PDNPs were
      discovered to be internalized through three specific pathways, that is, Caveolae
      , Arf6-dependent endocytosis, and Rab34-mediated macropinocytosis (55%, 20% and
      37% of uptake inhibition by nystatin, Arf6 knockdown, and rottlerin,
      respectively). Autophagy-mediated accumulation of PDNPs in lysosomes was observed
      and the formed PDA shells shedded in the lysosomes. Almost 40% of the NPs were
      transported out of cells via Rab8/10- and Rab3/26-mediated exocytosis pathways at
      our tested level. On the basis of these results, a novel combined cancer
      treatment strategy was further proposed using drug-loaded MSNs-PDA by (i)
      utilizing naturally intracellular mechanism-controlled PDA shedding for organelle
      targeted release of drugs in lysosomes to generate lysosome impairment and (ii)
      blocking the demonstrated exocytosis pathways for enhanced therapeutic efficacy.

PMID- 29058909
TI  - Switchable Surfactants for the Preparation of Monodisperse, Supported
      Nanoparticle Catalysts.
AB  - Synthesis methods for the preparation of monodisperse, supported nanoparticles
      remain problematic. Traditional synthesis methods require calcination following
      nanoparticle deposition to remove bound ligands and expose catalytic active
      sites. Calcination leads to significant and unpredictable growth of the
      nanoparticles resulting in polydisperse size populations. This undesired increase
      in nanoparticle size leads to a decrease in catalytic activity due to a loss of
      total surface area. In this work, we present the use of silylamines, a class of
      switchable solvents, for the preparation of monodisperse, supported
      nanoparticles. Silylamines are switchable molecules that convert between
      molecular and ionic forms by reaction with CO2. Upon addition of an alkane, the
      switchable solvent behaves as a switchable surfactant (SwiS). The SwiS is used to
      template nanoparticles to aid in synthesis and subsequently used to release
      nanoparticles for deposition onto a support material. The use of SwiS allowed for
      the preservation of nanoparticle diameter throughout the deposition process.
      Finally, it is demonstrated that supported gold nanoparticle catalysts prepared
      using SwiS are up to 300% more active in the hydrogenation of 4-nitrophenol than
      their traditionally prepared analogues.

PMID- 29058910
TI  - N-Deoxycholic acid-N,O-hydroxyethyl Chitosan with a Sulfhydryl Modification To
      Enhance the Oral Absorptive Efficiency of Paclitaxel.
AB  - Currently, the most prominent barrier to the success of orally delivered
      paclitaxel (PTX) is the extremely limited bioavailability of delivered
      therapeutic. In light of this issue, an amphiphilic sulfhydrylated N-deoxycholic
      acid-N,O-hydroxyethyl chitosan (TGA-DHC) was synthesized to improve the oral
      bioavailability of PTX. First, TGA-DHC demonstrated substantial loading of PTX
      into the inner hydrophobic core. A desirable enhancement in the bioavailability
      of PTX by TGA-DHC was verified by pharmacokinetic studies on rats against Taxol
      and non-sulfhydrylated DHC micelles. Moreover, cellular uptake studies revealed
      significant accumulation of TGA-DHC micelles encapsulating PTX or rhodamine-123
      into Caco-2 cells via clathrin/caveolae-mediated endocytosis and inhibition of P
      gp efflux of substrates. The results of the Caco-2 transport study further
      confirmed the mechanistic basis of TGA-DHC efficacy; which was attributed to
      permeabilized tight junctions, clathrin-mediated transcytosis across the
      endothelium, and inhibition of P-gp. Finally, in vitro mucoadhesion
      investigations on freshly excised rat intestine intuitively confirmed increased
      intestinal retention of drug-loaded TGA-DHC through thiol-mediated mucoadhesion.
      TGA-DHC has demonstrated the capability to overcome what is perhaps the most
      prominent barrier to oral PTX efficacy, low bioavailability, and serves as a
      prominent platform for oral delivery of P-gp substrates.

PMID- 29058911
TI  - Ruthenium-Catalyzed Remote C-H Sulfonylation of N-Aryl-2-aminopyridines with
      Aromatic Sulfonyl Chlorides.
AB  - A ruthenium-catalyzed remote sulfonylation at the C5 position of the pyridine
      group of N-aryl-2-aminopyridines with aromatic sulfonyl chlorides is described.
      The mechanistic and deuterium labeling studies clearly reveal that the
      ruthenametallacycle is a key intermediate in the reaction, which forms via the C
      H bond activation. The DFT calculation supports that the C5 position of the 2
      aminopyridine group carries a more negative charge (-0.304) as compared with
      other carbons in the metalacycle intermediate.

PMID- 29058912
TI  - Quantifying the Selective Modification of Au(111) Facets via Electrochemical and
      Electroless Treatments for Manipulating Gold Nanorod Surface Composition.
AB  - Manipulating the composition of a mixed alkylthiol self-assembled monolayer (SAM)
      modified gold surface using both electrochemical and electroless methods is
      demonstrated. Through the use of fluorophore labeled thiolated DNA and in situ
      fluorescence microscopy with a gold single crystal bead electrode, a procedure
      was developed to study and quantify the selective desorption of an alkylthiolate
      SAM. This method enabled a self-consistent measurement of the removal of the SAM
      from the 111 surface compared to the 100 surface region at various potentials. A
      20-fold increase in the electrochemical removal and replacement of the SAM from
      the 111 surface over the 100 surface was realized at -0.8 V/AgAgCl. A related
      procedure was developed for the solution-based electroless removal of the SAM
      using NaBH4 achieving a similar selectivity at the same potential. Unfortunately,
      in the electroless process fine control over the reducing potential was difficult
      to achieve. In addition, working in the presence of O2 complicates the solution
      potential measurement due to depolarization by the reduction of O2, resulting in
      a less clear relationship between selectivity and measured solution potential.
      Interestingly, the electrochemical method was not disturbed by the presence of
      O2. In preparation for work with Au nanorods, electrochemical measurements were
      performed in electrolyte that included 1 mM CTAB and was found to not interfere
      with this method. Preliminary results are promising for using this methodology
      for treatment of acid-terminated alkylthiol modified Au nanorods.

PMID- 29058913
TI  - Drug-Excipient Interactions in the Solid State: The Role of Different Stress
      Factors.
AB  - Understanding properties and mechanisms that govern drug degradation in the solid
      state is of high importance to ensure drug stability and safety of solid dosage
      forms. In this study, we attempt to understand drug-excipient interactions in the
      solid state using both theoretical and experimental approaches. The model active
      pharmaceutical ingredients (APIs) under study are carvedilol (CAR) and codeine
      phosphate (COP), which are known to undergo esterification with citric acid (CA)
      in the solid state. Starting from the crystal structures of two different
      polymorphs of each compound, we calculated the exposure and accessibility of
      reactive hydroxyl groups for a number of relevant crystal surfaces, as well as
      descriptors that could be associated with surface stabilities using molecular
      simulations. Accelerated degradation experiments at elevated temperature and
      controlled humidity were conducted to assess the propensity of different solid
      forms of the model APIs to undergo chemical reactions with anhydrous CA or CA
      monohydrate. In addition, for CAR, we studied the solid state degradation at
      varying humidity levels and also under mechano-activation. Regarding the relative
      degradation propensities, we found that variations in the exposure and
      accessibility of molecules on the crystal surface play a minor role compared to
      the impact of molecular mobility due to different levels of moisture. We further
      studied drug-excipient interactions under mechano-activation (comilling of API
      and CA) and found that the reaction proceeded even faster than in physical powder
      mixtures kept at accelerated storage conditions.

PMID- 29058914
TI  - TiO2-Based Nanomaterials for the Production of Hydrogen and the Development of
      Lithium-Ion Batteries.
AB  - The photocatalytic activity of different titanium oxide nanowires containing gold
      (Au@TiO2NWs), and gold-graphene (Au@TiO2NWs-graphene), was evaluated by studying
      the reaction of hydrogen production by water splitting under UV-vis light. The
      composites showed high surface areas, with values above 300 m2 per gram, even
      after the incorporation of gold and graphene on the surface of titanium oxide
      nanowires. The highest hydrogen production of Au@TiO2NWs was 1436 MUmol h-1 g-1,
      under irradiation at 400 nm, and with a gold loading of 10 wt %. This
      photocatalytic activity was 11.5 times greater than that shown by the unmodified
      TiO2NWs. For the Au@TiO2NWs-graphene composites, the highest hydrogen amount
      obtained was 1689 MUmol h-1 g-1, at loadings of 10 and 1 wt % of gold and
      graphene, respectively. The photocatalytic activity of the gold-graphene
      compounds was 1.2 times greater than that shown by the titanium oxide catalysts
      and 13.5 times higher than the bare TiO2NWs. Even at wavelengths greater than 500
      nm, the compounds exhibited yields of hydrogen above 1000 MUmol h-1 g-1,
      demonstrating the high catalytic activity of the compounds. In addition, TiO2
      based materials are of great interest for energy storage and conversion devices,
      in particular for rechargeable lithium ion batteries. TiO2 has a significant
      advantage due to its low volume change (<4%) during the Li ion
      insertion/desertion process, short paths for fast lithium ion diffusion, and
      large exposed surface, offering more lithium insertion channels. However, the
      relatively low theoretical capacity and electrical conductivity of TiO2 greatly
      hamper its practical application. In this work, free-standing electrodes composed
      by TiO2NWs and carbon nanotubes, CNT@TiO2NWs, were used as anode materials for Li
      ion batteries. As a result, the electronic conductivity and mechanical properties
      of the composite were greatly improved and a good cycling performance was
      obtained in these batteries. This research shows the potential of TiO2-based
      materials for the development of new catalysts for hydrogen production and energy
      storage systems.

PMID- 29058915
TI  - Mass Spectrometric Approaches for the Analysis of Phytosterols in Biological
      Samples.
AB  - Plant sterols (phytosterols) are important structural components of plant
      cellular membranes, and they play a major role during development and metabolism.
      They have health-associated benefits, especially in lowering blood cholesterol
      levels. Because of their many health claims, there is a growing interest in their
      analysis. Although various analytical strategies have been employed in analyzing
      phytosterols, chromatography linked to mass spectrometry (MS) is superior due to
      its sensitivity. Furthermore, specificity and selectivity are enhanced by
      utilizing tandem mass spectrometry (MS/MS). This article reviews the various mass
      spectrometric strategies used for the analysis of phytosterols. It highlights the
      applications and limitations associated with each MS strategy in various sample
      matrixes such as plant, human, animal, food, and dietary supplements. GC-MS was
      historically the method of choice for analysis; however, the derivatization step
      rendered it tedious and time-consuming. On the other hand, liquid chromatography
      coupled to MS (LC-MS) simplifies the analysis. Many ionization techniques have
      been used, namely, electrospray ionization (ESI), atmospheric pressure chemical
      ionization (APCI), and atmospheric pressure photoionization (APPI). APCI showed
      superiority in terms of ion intensity and consistency in ion formation, primarily
      forming [M + H - H2O]+ ions rather than [M + H]+. In addition, matrix assisted
      laser desorption ionization (MALDI) as well as ambient mass spectrometry such as
      direct analysis in real time (DART) have also been evaluated.

PMID- 29058917
TI  - On-Demand Spin-Orbit Interaction from Which-Layer Tunability in Bilayer Graphene.
AB  - Spin-orbit interaction (SOI) that is gate-tunable over a broad range is essential
      to exploiting novel spin phenomena. Achieving this regime has remained elusive
      because of the weakness of the underlying relativistic coupling and lack of its
      tunability in solids. Here we outline a general strategy that enables
      exceptionally high tunability of SOI through creating a which-layer spin-orbit
      field inhomogeneity in graphene multilayers. An external transverse electric
      field is applied to shift carriers between the layers with strong and weak SOI.
      Because graphene layers are separated by subnanometer scales, exceptionally high
      tunability of SOI can be achieved through a minute carrier displacement. A
      detailed analysis of the experimentally relevant case of bilayer graphene on a
      semiconducting transition metal dichalchogenide substrate is presented. In this
      system, a complete tunability of SOI amounting to its ON/OFF switching can be
      achieved. New opportunities for spin control are exemplified with electrically
      driven spin resonance and topological phases with different quantized intrinsic
      valley Hall conductivities.

PMID- 29058918
TI  - Spatial Factors for Triplet Fusion Reaction of Singlet Oxygen Photosensitization.
AB  - First-principles quantum-chemical description of photosensitized singlet oxygen
      generation kinetics is challenging because of the intrinsic complexity of the
      underlying triplet fusion process in a floppy molecular complex with open-shell
      character. With a quantum-chemical kinetic model specifically tailored to deal
      with this problem, the reaction rates are investigated as a function of
      intermolecular incidence direction, orientation, and distance between O2 and the
      photosensitizer. The adopted photosensitizer, 6-azo-2-thiothymine, combines
      practical interest and prototypical variability. The study quantitatively
      determined maximum singlet oxygen generation rates for 15 incidence/orientation
      directions, showing that they span 5 orders of magnitude between the largest and
      the smallest rate. Such information may provide a hands-on guideline for the
      experimental molecular design of new photosensitizers as well as further higher
      level theoretical research.

PMID- 29058916
TI  - Resolubilization of Protein from Water-Insoluble Phlorotannin-Protein Complexes
      upon Acidification.
AB  - Marine phlorotannins (PhT) from Laminaria digitata might protect feed proteins
      from ruminal digestion by formation of insoluble non-covalent tannin-protein
      complexes at rumen pH (6-7). Formation and disintegration of PhT-protein
      complexes was studied with beta-casein (random coil) and bovine serum albumin
      (BSA, globular) at various pH. PhT had similar binding affinity for beta-casein
      and BSA as pentagalloyl glucose, as studied by fluorescence quenching. The
      affinity of PhT for both proteins was independent of pH (3.0, 6.0, and 8.0). In
      the presence of PhT, the pH range for precipitation of tannin-protein complexes
      widened to 0.5-1.5 pH units around the isoelectric point (pI) of the protein.
      Complete protein resolubilization from insoluble PhT-protein complexes was
      achieved at pH 7 and 2 for beta-casein and BSA, respectively. It was demonstrated
      that PhT modulate the solubility of proteins at neutral pH and that
      resolubilization of PhT-protein complexes at pH deviating from pI is mainly
      governed by the charge state of the protein.

PMID- 29058919
TI  - Capillary-Force-Assisted Clean-Stamp Transfer of Two-Dimensional Materials.
AB  - A simple and clean method of transferring two-dimensional (2D) materials plays a
      critical role in the fabrication of 2D electronics, particularly the
      heterostructure devices based on the artificial vertical stacking of various 2D
      crystals. Currently, clean transfer techniques rely on sacrificial layers or
      bulky crystal flakes (e.g., hexagonal boron nitride) to pick up the 2D materials.
      Here, we develop a capillary-force-assisted clean-stamp technique that uses a
      thin layer of evaporative liquid (e.g., water) as an instant glue to increase the
      adhesion energy between 2D crystals and polydimethylsiloxane (PDMS) for the pick
      up step. After the liquid evaporates, the adhesion energy decreases, and the 2D
      crystal can be released. The thin liquid layer is condensed to the PDMS surface
      from its vapor phase, which ensures the low contamination level on the 2D
      materials and largely remains their chemical and electrical properties. Using
      this method, we prepared graphene-based transistors with low charge-neutral
      concentration (3 * 1010 cm-2) and high carrier mobility (up to 48 820 cm2 V-1 s-1
      at room temperature) and heterostructure optoelectronics with high operation
      speed. Finally, a capillary-force model is developed to explain the experiment.

PMID- 29058920
TI  - [Is it possible to avoid axillary dissection?]
AB  - The essential aim of oncology surgery including breast cancer is to remove the
      malignant tumour and lymph nodes. For many decades, dissection of axillary lymph
      nodes has been a common part of mastectomy, virtually the only surgical procedure
      in breast cancer treatment until the 90ies of the previous century. Although
      mastectomy has been replaced with breast preserving procedures, axillary
      dissection remained an integral part of the surgery. Sentinel lymph node biopsy
      (SLNB) has introduced a revolutionary change in breast cancer treatment in the
      axilla, replacing dissection in clinically negative axillary nodes. As a result,
      the number of radical procedures in the axilla was significantly limited, as well
      as the incidence of serious complications that may have a negative impact on the
      quality of life of the patients. As shown by other studies, the number of
      dissections can be reduced even further. Subsequent axillary dissection is
      unnecessary where the sentinel nodes contain only malignant cells,
      micrometastases and even a limited number of macrometastases. SLNB can also be
      used in a selected group of patients after neoadjuvant chemotherapy.Key words:
      breast carcinoma - axillary dissection - sentinel lymph node - micrometastases -
      macrometastases.

PMID- 29058921
TI  - [Internal mammary lymph nodes in early stage breast cancer].
AB  - Internal mammary nodes (IMN) in early stage breast cancer are a still unresolved
      issue. Their involvement has a crucial impact on the staging as well as prognosis
      of the breast cancer patients. The reported incidence of IMN drainage in the
      process of detecting the axillary sentinel node is about 20% depending on the
      tracer application technique. However, the IMN drainage itself apparently has no
      effect on the prognosis even when the nodes are left without biopsy or
      radiotherapy. The major predictive factor for the presence of metastases in IMN
      is the presence of metastases in axillary lymph nodes. Studies evaluating
      adjuvant IMN radiotherapy have shown inconsistent outcomes. The generally
      accepted trend towards less extensive locoregional procedures in breast cancer
      treatment will apparently affect the IMN, as well, given that new systemic
      treatment will probably compensate for uncertainties in IMN management.Key words:
      breast cancer internal mammary nodes radiotherapy.

PMID- 29058922
TI  - [Satisfaction and overall quality of life in BRCA positive women after
      prophylactic surgeries].
AB  - INTRODUCTION: Genetic mutations are responsible for 5-10% of all breast and
      ovarian carcinomas, while most of them are caused by a mutation of the BRCA gene.
      Women with this type of mutation have a lifetime risk of breast and ovarian
      cancer and therefore, they require very intensive medical care, including
      surgical prevention. Specifically, prophylactic bilateral mastectomy and
      prophylactic salpingo-oophorectomy are done, which undoubtedly decrease the
      riskof cancer. The aim of this review article is to inform healthcare
      professionals and the general public about the satisfaction of BRCA positive
      women with their decision to undergo these prophylactic surgeries, and also about
      the impact of these procedures on sexuality, menopausal symptoms, mental health
      and the overall quality of life. METHODS: Search of original studies and review
      articles onthe influence of prophylactic surgeries on the life of women with BRCA
      genemutation. RESULTS: In general, although some changes are observed after the
      prophylactic surgeries, the overall quality of life does not change. A
      significant reduction in anxiety and fear of cancer is observed after both
      prophylactic bilateral mastectomy andprophylactic bilateral salpingo
      oophorectomy, providing great psychological relief to the affected women.
      However, prophylactic bilateral salpingo-oophorectomy causes premature menopause
      in premenopausal women at the time of surgery and the associated occurrence of
      menopausal symptoms. Some of the symptoms can be significantly reduced by hormone
      replacement therapy but will not be eliminated altogether. In postmenopausal
      women, no or minimal worsening of menopausal symptoms was reported. After
      prophylactic bilateral mastectomy, particularly appearance-related problems were
      observed. In both types of surgery, sexual problems were also observed.
      CONCLUSION: The relief of reducingthe risk of cancerappears to be so great and so
      important for women that it outweighs the other negative effects of these
      prophylactic procedures.Key words: BRCA1/2 mutation - breast cancer - ovarian
      cancer - prophylactic bilateral salpingo-oophorectomy - prophylactic bilateral
      mastectomy.

PMID- 29058923
TI  - [Microscopic tumor cells in re-excision tissue by conservative surgery in breast
      cancer].
AB  - INTRODUCTION: Conservative procedures in early breast carcinoma are a safe
      alternative to mastectomy. The resection line is controversial, as well as the
      presence of residual malignant cells in the breast after excision and their
      influence on local recurrence. The aim of the study was to assess the presence of
      residual cells in re-excised tissues near positive resection lines, in the
      distance up to 2 mm, and 2-5 mm. The distance of more than 5 mm was evaluated as
      free margin. METHOD: All patients operated on in Atlas Hospital from 2004 to 2008
      using conservative surgery were included in study. The resection line and the
      presence of residual malignant cells were followed in positive margins and in the
      distance of the resection line from the tumour up to 2 mm, and 2-5 mm. RESULTS:
      The conservative procedure was indicated 330 times, and 78 patients were re
      operated for insufficiently free margins. The conservative procedure was
      completed 311 times, and mastectomy was done as the final procedure in 19 cases.
      Positive resection line was found 10 times. Distance up to 2 mm occurred 12 times
      and 25 mm 56 times. In all re-operated patients, presence of malignant cells in
      the re-excised tissue was found 31 times (39.7%). Repeated surgery for positive
      line, i.e. tumour present in the resection line, was done 10 times while
      malignant cells were found in all patients; for the distance up 2 mm, repeated
      surgery was done 12 times and 3 cases were positive (25%). For the distance of 2
      5 mm, repeated excision occurred 56 times and 18 cases were positive, i.e. 32.1%.
      CONCLUSION: For the resection line "no tumour in contact with ink", presence of
      malignant cells in breast tissue must be expected in one third of the cases.Key
      words: breast carcinoma - conservative surgery - residual malignant cells.

PMID- 29058924
TI  - [Magnetic resonance imaging in preoperative diagnosis of invasive lobular
      carcinomas of the breast - analysis of 230 cases].
AB  - INTRODUCTION: In breast cancer patients, magnetic resonance imaging (MRI) is a
      supportive method characterized by high sensitivity. Its indications in the
      preoperative assessment are not clearly defined. More likely to benefit from
      preoperative MRI are younger women, women with a dense breast on mammography and
      patients with invasive lobular carcinoma (ILC). The aim of this study was to
      assess utilization of MRI and resulting benefits in preoperative tumour staging
      of ILC in patients treated in our institution. METHODS: A retrospective
      evaluation of medical records of all patients with bioptically proven and
      primarily surgically treated ILC through the years 20142016. RESULTS: Overall,
      230 patients were evaluated, among them 131 (57.0%) underwent MRI. These patients
      were significantly younger than patients without MRI. The results of MRI were as
      follows: in 28.2% a small unicentric lesion, in 41.2% large infiltration or
      multifocality, and in 30.5% suspicion of multicentricity. The proportion of
      conservative surgeries and re-resections did not differ between the patients with
      and without MRI. The subgroup of patients with a small unicentric lesion on MRI
      showed a higher proportion of conservative surgeries and fewer re-resections
      compared to the other subgroups. In 41 women (31.3%) the MRI finding resulted in
      further assessments; in 29 (22.1%) an additional biopsy was done, with a
      malignant result in the ipsilateral breast in 8 cases and in the contralateral
      breast in 3 cases. The MRI finding had a substantial impact on surgery in 35
      patients (26.7%) of whom it was evaluated as clinically beneficial in 23 (65.7%)
      cases. CONCLUSION: At our institution, more than a half of patients with ILC
      undergo MRI preoperatively. The finding has an impact on the scope of the surgery
      in approximately one fourth of the cases, being clinically beneficial in most of
      them. However, a high frequency of additional imaging assessments and biopsies
      should be taken into account. Due to the low specificity of MRI, every suspicious
      lesion has to be bioptically verified to avoid inappropriate surgery and patient
      harm.Key words: breast cancer - invasive lobular carcinoma - magnetic resonance
      imaging - occult lesion - biopsy.

PMID- 29058925
TI  - [A new perspective on axillary dissection in situations of metastatic sentinel
      node].
AB  - INTRODUCTION: Breast cancer is the most common malignant disease in women and
      represents a worldwide problem. Up-to-date diagnostics methods, mammography
      screening and complex treatments have resulted in a substantial reduction of
      mortality rates. However, the incidence of the disease keeps growing constantly,
      although in a moderate way. The struggle against this disease has several levels,
      such as prevention, primary tumour therapy as well as the management of recurrent
      or generalized disease. Therefore, it is very significant to evaluate the
      prognosis on the basis of biological characteristics of the tumour and to
      determine the right individual therapy in each patient. AIM OF THE STUDY: Our aim
      was to determine a group of patients with malignant breast disease based on
      biological characteristics of the tumour who can be treated without axillary
      exenteration even with a metastasis in the sentinel lymph node, thereby reducing
      the morbidity associated with this surgery, without worsening the prognosis.
      METHOD: The research project lasted from June 2012 to June 2015. It was a
      prospective randomized study where the main investigated group consisted of women
      with primarily surgically treated mammary cancer undergoing sentinel lymph node
      biopsy (SNB) during their surgery. These patients were divided into three groups:
      group 1 - positive SNB without axillary exenteration (axillary dissection - AD);
      group 2 - positive SNB with AD; and group 3 - negative SNB. Group 4 consisted of
      patients with primarily performed AD. We investigated statistically significant
      prognostic factors of metastatic lymph nodes and early disease progression. The
      results were statistically processed and differences between individual groups
      were evaluated, determining prognostically usable biological characteristics of
      the tumour in connection with metastases in lymph nodes and progression-free
      survival. RESULTS: The study included 214 patients with breast cancer. No
      metastases of axillary lymph nodes were found in 136 patients (64%); on the other
      hand, 78 patients (36%) had positive axillary lymph nodes and included: 28 (13%)
      patients with a micrometastasis in the sentinel lymph node; 38 (17%) patients
      with 13 positive lymph nodes; 8 (4%) patients with 49 positive lymph nodes; and 4
      (2%) patients had more than 10 metastatic lymph nodes. A statistically
      significant difference with respect to metastatic lymph node involvement was
      found for the tumour size, expression of oestrogen receptors, proliferative
      activity and grading. CONCLUSION: The following prognostic factors of metastatic
      lymph nodes and early disease progression were shown to be statistically
      significant: tumour size over 2 cm, negative expression of oestrogen receptors,
      tumours with moderate and high proliferative activity, and tumour grades G2 and
      G3. In the course of the three years of this study, no regional recurrence was
      found in axillary lymph nodes in any patient, and therefore, it clearly follows
      that the completion of axillary exenteration can be omitted in the case of tumour
      sizes below 2 cm, present expression of oestrogen receptors, low proliferative
      activity and grade 1 even if one or two positive sentinel lymph nodes are
      present, provided that adjuvant radiation therapy can be used. Also, axillary
      exenteration is not needed if a micrometastasis or isolated tumour cells are
      found in the sentinel lymph node.Key words: breast cancer - sentinel lymph node
      biopsy - axillary exenteration - prognostic factors.

PMID- 29058926
TI  - [Breast angiosarcoma induced by radiotherapy - surgical treatment options and
      review of literature].
AB  - INTRODUCTION: Radiation-induced angiosarcoma is a rare but very aggressive
      tumour. The highest risk of sarcoma development is in patients after breast
      conserving surgery.Case 1: The 66 years old patient underwent radical mastectomy
      with axillary dissection because of ductal carcinoma with consequent
      radiotherapy, chemotherapy and hormonal therapy. After 6 years, high-grade
      angiosarcoma was diagnosed and resected with negative resection margins. Within
      subsequent 24 months, additional three radical re-excisions were performed
      because of repeated sarcoma recurrence. 29 months from the diagnosis of the first
      sarcoma, another radical re-excision was performed, this time with positive
      resection margins and with consequent disease progression. The patient died three
      years after the first angiosarcoma diagnosis.Case 2: The 68 years old patient
      underwent breast-conserving surgery with axillary dissection because of ductal
      carcinoma and radiotherapy. Breast colour changes were observed 6 years later;
      radical mastectomy was performed after additional 16 months due to locally
      advanced angiosarcoma. Given positive resection margin, radical re-excision with
      musculocutaneous musculus latissimus dorsi flap was done. 24 months later, a
      small sarcoma recurrence was detected near the upper resection margin, which was
      managed by radical re-excision. 52 months after radical operation, a metastasis
      was diagnosed by means of PET/CT in the contralateral axilla. Radical axillary
      dissection was performed (two metastases were found in axillary lymph nodes).
      According to follow-up, the patient has been free of any recurrence for 66 months
      from the radical surgery. CONCLUSION: Recommendations regarding the management of
      radiotherapy induced breast angiosarcoma are very vague due to limited evidence.
      Radical surgical excision with negative resection margins (potentially with
      complementary flap reconstruction) presents the fundamental approach to breast
      angiosarcoma.Key words: radiation-induced angiosarcoma - breast cancer - surgery.

PMID- 29058927
TI  - Perceived entitlement causes discrimination against attractive job candidates in
      the domain of relatively less desirable jobs.
AB  - People generally hold positive stereotypes of physically attractive people and
      because of those stereotypes often treat them more favorably. However, we propose
      that some beliefs about attractive people, specifically, the perception that
      attractive individuals have a greater sense of entitlement than less attractive
      individuals, can result in negative treatment of attractive people. We examine
      this in the context of job selection and propose that for relatively less
      desirable jobs, attractive candidates will be discriminated against. We argue
      that the ascribed sense of entitlement to good outcomes leads to perceptions that
      attractive individuals are more likely to be dissatisfied working in relatively
      less desirable jobs. When selecting candidates for relatively less desirable
      jobs, decision makers try to ascertain whether a candidate would be satisfied in
      those jobs, and the stereotype of attractive individuals feeling entitled to good
      outcomes makes decision makers judge attractive candidates as more likely to be
      dissatisfied in relatively less (but not more) desirable jobs. Consequently,
      attractive candidates are discriminated against in the selection for relatively
      less desirable jobs. Four experiments found support for this theory. Our results
      suggest that different discriminatory processes operate when decision makers
      select among candidates for relatively less desirable jobs and that attractive
      people might be systematically discriminated against in a segment of the
      workforce. (PsycINFO Database Record

PMID- 29058928
TI  - A brief parent-focused intervention to improve preschoolers' conversational
      skills and school readiness.
AB  - Preschool children's use of decontextualized language, or talk about abstract
      topics beyond the here-and-now, is predictive of their kindergarten readiness and
      is associated with the frequency of parents' own use of decontextualized
      language. Does a brief, parent-focused intervention conveying the importance of
      decontextualized language cause parents to increase their use of these
      conversations, and as a result, their children's? We examined this question by
      randomly assigning 36 parents of 4-year-old children into a decontextualized
      language training condition or a no-treatment control condition and used mixed
      effects modeling to measure change (from baseline) in parent and child
      decontextualized language at 4 subsequent home mealtimes during the following
      month (N = 174 interactions including the baseline). Compared with the control
      condition, training condition dyads significantly increased their
      decontextualized talk and maintained these gains for the month following
      implementation. Furthermore, trained dyads generalized the program content to
      increase their use of similarly decontextualized, yet untrained conversations.
      These results demonstrate that an abstract feature of the input is malleable, and
      introduces a simple, scalable, and replicable approach to increase a feature of
      child language known to be foundational for children's school readiness.
      (PsycINFO Database Record

PMID- 29058929
TI  - Selectivity in toddlers' behavioral and emotional reactions to prosocial and
      antisocial others.
AB  - Whereas some evidence suggests that toddlers consider targets' deservingness when
      deciding whom to help, other research demonstrates that toddlers help
      indiscriminately. The present findings shed light on this discrepancy by
      demonstrating that although toddlers do exhibit selectivity in giving behaviors,
      their emotional responses are comparatively indiscriminate. Specifically, in
      Experiment 1, 20-month-olds (N = 64) were more likely to give preferred toys to
      prosocial versus antisocial puppets, and more likely to withhold toys from
      antisocial versus prosocial puppets. Experiment 2 (N = 64) ruled out low-level
      explanations for the effects observed in Experiment 1, demonstrating that
      toddlers do not show the same effects when puppets' toy preferences are unclear.
      Despite providing evidence for selectivity in giving behaviors, across both
      experiments, toddlers were happier after giving than before giving, regardless of
      what they gave or whom they gave to. These results reveal the possibility of a
      divergence in early prosociality: Toddlers' giving behaviors are responsive to
      recipient deservingness, but their after-the-fact emotional reactions are
      responsive to giving acts themselves. Results are discussed in terms of their
      relevance to the debate regarding whether toddlers' early prosocial behaviors are
      discriminate versus indiscriminate. (PsycINFO Database Record

PMID- 29058930
TI  - NR3C1 methylation as a moderator of the effects of maternal support and stress on
      insecure attachment development.
AB  - We examined the prediction that the interaction between Glucocorticoid Receptor
      Gene (NR3C1) methylation, stress, and experienced maternal support predicts
      anxious and avoidant attachment development. This was tested in a general
      population sample of 487 children and adolescents (44% boys, Mage = 11.84, SDage
      = 2.4). These children were followed over a period of 18 months. In line with the
      prediction, we found that NR3C1 methylation moderates the effect of maternal
      support during stress on anxious attachment development 18 months later. More
      stressed children who experienced less maternal support reported increased
      anxious attachment when their NR3C1 gene was highly methylated. This effect could
      not be explained by children's level of psychopathology. No effects were found
      for attachment avoidance. These data provide the first prospective evidence that
      epigenetic processes are involved in attachment development. (PsycINFO Database
      Record

PMID- 29058931
TI  - Genetic and environmental contributions to the development of childhood
      aggression.
AB  - Longitudinal data from a large sample of twins participating in the Netherlands
      Twin Register (n = 42,827, age range 3-16) were analyzed to investigate the
      genetic and environmental contributions to childhood aggression. Genetic auto
      regressive (simplex) models were used to assess whether the same genes are
      involved or whether new genes come into play as children grow up. The authors
      compared 2 different simplex models to disentangle potentially changing
      behavioral expressions from changes in genetic and environmental effects. One
      model provided estimates of genetic and environmental effects at the level of
      individual aggression questionnaire items, and the other model assessed the
      effects at the level of an aggression sum score computed from the individual
      items. The results from both models provided evidence for largely stable genetic
      effects throughout childhood. The results also highlighted the differential
      heritability of the different indicators of aggression measured with the
      Childhood Behavior Checklist, with destruction of property showing a very high
      genetic component during early childhood and fighting behaviors being more
      heritable in early adolescence. (PsycINFO Database Record

PMID- 29058932
TI  - Intergenerational continuity in high-conflict family environments: Investigating
      a mediating depressive pathway.
AB  - Emerging evidence suggests that family conflict shows continuity across
      generations and that intergenerational family conflict can be more intense and
      deleterious than conflict experienced in a single generation. However, few
      investigations have identified etiological mechanisms by which family conflict is
      perpetuated across generations. Addressing this limitation, we sampled 246
      families from a multigenerational, high-risk, longitudinal study of parents (G1s)
      and their children (G2s), followed from adolescence to adulthood as well as the
      children (G3s) of G2 targets. Specifically, the current study examined whether
      G2s' depressive symptoms measured at multiple time points across development
      explained continuity in family conflict from 1 generation (G1-G2) to the next (G2
      G3). Results revealed that after controlling for externalizing symptoms,
      depressive symptoms served as mediators of intergenerational family conflict in
      both men and women, but in different ways. Specifically, G2 women's young
      adulthood represented a period of vulnerability in which G2 depressive symptoms
      were especially likely to mediate intergenerational continuity in family
      conflict. Additionally, in both men and women, higher G1-G2 family conflict was
      associated with higher depressive symptoms that persisted from adolescence into
      young adulthood and then subsequently predicted the development of G2-G3 family
      conflict. Results did not support the hypothesis that G2 partner depressive
      symptoms moderated the relation between G2 depressive symptoms and G2-G3 family
      conflict. Implications of findings regarding the roles that G2 gender and G2
      depressive symptoms play in the intergenerational transmission of family conflict
      are discussed. (PsycINFO Database Record

PMID- 29058933
TI  - Fitting handled objects into apertures by 17- to 36-month-old children: The
      dynamics of spatial coordination.
AB  - Handled artifacts are ubiquitous in human technology, but how young children
      engage in spatially coordinated behaviors with these artifacts is not well
      understood. To address this issue, children (N = 30) from 17-36 months were
      studied with motion tracking technology as they fit the distal segment of a
      handled artifact into a slot. The handle was orthogonal to the distal segment.
      Results revealed developmental differences in prospective control tied to the
      artifact's spatial structure. Although all children accomplished fitting, younger
      children first oriented the handle and then the distal segment (and only after
      the distal segment contacted the slot), whereas children by 3 years of age
      oriented the handle and distal segment simultaneously in different spatial
      planes, prior to the distal segment contacting the slot. Choosing an effective
      grip posture proved difficult for all children. Results are discussed in terms of
      how children begin to relate their actions to the 3-dimensional spatial structure
      of handled objects and the prospective control of object movement in multiple
      spatial planes. (PsycINFO Database Record

PMID- 29058934
TI  - Interparental conflict and children's social problems: Insecurity and friendship
      affiliation as cascading mediators.
AB  - Although social difficulties have been identified as sequelae of children's
      experiences with interparental conflict and insecurity, little is known about the
      specific mechanisms underlying their vulnerability to social problems. Guided by
      emotional security theory, this study tested the hypothesis that children's
      emotional insecurity mediates associations between interparental conflict and
      their social difficulties by undermining their affiliative goals in best
      friendships. Participants included 235 families with the first of 5 measurement
      occasions over a 10-year period occurring when children were in kindergarten
      (mean age = 6 years). Findings from the lagged latent difference score analyses
      indicated that intensification of multi-method assessment of interparental
      conflict during the early school years predicted subsequent increases in
      children's emotional insecurity 5 years later in adolescence. In the latter part
      of the cascade, rises in emotional insecurity predicted decreases in adolescent
      friendship affiliation, which, in turn, were specifically associated with
      declines in social competence. The specificity of this cascade of changing
      processes in predicting social problems was supported by the robustness of the
      findings after the inclusion of static measures of each construct as predictors,
      parent-child relationship insecurity as a covariate, and increases in children's
      internalizing symptoms as an alternative outcome. (PsycINFO Database Record

PMID- 29058935
TI  - Perceived age discrimination across age in Europe: From an ageing society to a
      society for all ages.
AB  - Ageism is recognized as a significant obstacle to older people's well-being, but
      age discrimination against younger people has attracted less attention. We
      investigate levels of perceived age discrimination across early to late
      adulthood, using data from the European Social Survey (ESS), collected in 29
      countries (N = 56,272). We test for approximate measurement invariance across
      countries. We use local structural equation modeling as well as moderated
      nonlinear factor analysis to test for measurement invariance across age as a
      continuous variable. Using models that account for the moderate degree of
      noninvariance, we find that younger people report experiencing the highest levels
      of age discrimination. We also find that national context substantially affects
      levels of ageism experienced among older respondents. The evidence highlights
      that more research is needed to address ageism in youth and across the life span,
      not just old adulthood. It also highlights the need to consider factors that
      differently contribute to forms of ageism experienced by people at different life
      stages and ages. (PsycINFO Database Record

PMID- 29058936
TI  - Mothers' dispositional distress reactivity as a predictor of maternal support
      following momentary fluctuations in children's aversive behavior.
AB  - Given that maternal support promotes healthy social and emotional development in
      early childhood, it is important to understand the predictors of such support,
      especially during emotional challenges. In this study, mothers' dispositional
      distress reactivity (i.e., the tendency toward experiencing distress in response
      to children's negative emotions and behavior) was assessed as a predictor of
      maternal support in a given moment when children showed within-person
      fluctuations in aversive behavior (i.e., negative affect and disruptive
      behaviors) in concurrent and prior moments. Data were collected when children
      were 33 months of age. Mothers (N = 128) reported on their distress reactivity,
      and maternal support and child aversive behavior were coded in 15-s intervals
      during a 5-min snack-delay task. As hypothesized, multilevel models revealed that
      mothers' dispositional distress reactivity predicted decreases in maternal
      support when children showed within-person increases in aversive behavior in the
      prior 15-s interval but not in the concurrent interval. Findings highlight the
      importance of investigating the contributions of maternal dispositional
      tendencies to moment-to-moment changes in parenting behavior during moderate,
      everyday challenges with young children. (PsycINFO Database Record

PMID- 29058938
TI  - The reasons young children give to peers when explaining their judgments of moral
      and conventional rules.
AB  - Moral justifications work, when they do, by invoking values that are shared in
      the common ground of the interlocutors. We asked 3- and 5-year-old peer dyads (N
      = 144) to identify and punish norm transgressors. In the moral condition, the
      transgressor violated a moral norm (e.g., by stealing); in the social rules
      condition, she/he violated a context-specific rule (e.g., by placing a yellow toy
      in a green box, instead of a yellow box). Children in both age groups justified
      their punishment in the social rules condition mostly by referring to the rule
      (e.g., "He must put yellow toys in the yellow box"). In contrast, in the moral
      condition they mostly justified their punishment by simply referring to the
      observed fact (e.g., "He stole"), seeing no need to state the norm involved
      (e.g., "He must not steal"), presumably because they assumed this as part of
      their moral common ground with their partner. These results suggest that
      preschoolers assume certain common ground moral values with their peers and use
      these in formulating explicit moral judgments and justifications. (PsycINFO
      Database Record

PMID- 29058939
TI  - Tests of an exemplar-memory model of classification learning in a high
      dimensional natural-science category domain.
AB  - Experiments were conducted in which novice participants learned to classify
      pictures of rocks into real-world, scientifically defined categories. The
      experiments manipulated the distribution of training instances during an initial
      study phase, and then tested for correct classification and generalization
      performance during a transfer phase. The similarity structure of the to-be
      learned categories was also manipulated across the experiments. A low-parameter
      version of an exemplar-memory model, used in combination with a high-dimensional
      feature-space representation for the rock stimuli, provided good overall accounts
      of the categorization data. The successful accounts included (a) predicting how
      performance on individual item types within the categories varied with the
      distributions of training examples, (b) predicting the overall levels of
      classification accuracy across the different rock categories, and (c) predicting
      the patterns of between-category confusions that arose when classification errors
      were made. The work represents a promising initial step in scaling up the
      application of formal models of perceptual classification learning to complex
      natural-category domains. We discuss further steps for making use of the model
      and its associated feature-space representation to search for effective
      techniques of teaching categories in the science classroom. (PsycINFO Database
      Record

PMID- 29058937
TI  - Inhibitory control in siblings discordant for exposure to maternal smoking during
      pregnancy.
AB  - Maternal smoking during pregnancy (SDP) has been linked to poorer offspring
      executive function across development, but SDP does not occur independent of
      other familial risk factors. As such, poor and inconsistent control for potential
      confounds, notably shared familial (i.e., genetic and environmental) confounds,
      preclude concluding causal effects of SDP on child outcomes. We examined the
      within-family association between SDP and one component of executive function,
      inhibitory control, in a sample of families (N = 173) specifically selected for
      sibling pairs discordant for exposure to SDP. Thus, the present study examines if
      the SDP-inhibitory control association withstands rigorous control for potential
      child and familial confounds. 79% of the variation in child inhibitory control
      was attributable to within-family differences and 21% was attributable to
      differences between families, indicating that the variability in inhibitory
      control was primarily a function of differences between siblings rather than
      differences across families. Further, the association between SDP and inhibitory
      control was fully attenuated when confounds were considered. These findings
      suggest that co-occurring vulnerabilities act as more salient risk factors for
      poorer child inhibitory control than SDP and may serve as effective targets of
      interventions seeking to improve children's inhibitory control in families with
      nicotine dependent mothers. (PsycINFO Database Record

PMID- 29058940
TI  - Much ado about aha!: Insight problem solving is strongly related to working
      memory capacity and reasoning ability.
AB  - A battery comprising 4 fluid reasoning tests as well as 13 working memory (WM)
      tasks that involved storage, recall, updating, binding, and executive control,
      was applied to 318 adults in order to evaluate the true relationship of reasoning
      ability and WM capacity (WMC) to insight problem solving, measured using 40
      verbal, spatial, math, matchstick, and remote associates problems (insight
      problems). WMC predicted 51.8% of variance in insight problem solving and
      virtually explained its almost isomorphic link to reasoning ability (84.6% of
      shared variance). The strong link between WMC and insight pertained generally to
      most WM tasks and insight problems, was identical for problems solved with and
      without reported insight, was linear throughout the ability levels, and was not
      mediated by age, motivation, anxiety, psychoticism, and openness to experience.
      In contrast to popular views on the sudden and holistic nature of insight, the
      solving of insight problems results primarily from typical operations carried out
      by the basic WM mechanisms that are responsible for the maintenance, retrieval,
      transformation, and control of information in the broad range of intellectual
      tasks (including fluid reasoning). Little above and beyond WM is unique about
      insight. (PsycINFO Database Record

PMID- 29058941
TI  - Implications of individual differences in on-average null effects.
AB  - Most psychological models are intended to describe processes that operate within
      each individual. In many research areas, however, models are tested by looking at
      results averaged across many individuals, despite the fact that such averaged
      results may give a misleading picture of what is true for each one. We consider
      this conundrum with respect to the interpretation of on-average null effects.
      Specifically, even though an experimental manipulation might have no effect on
      average across individuals, it might still have demonstrable effects-albeit in
      opposite directions-for many or all of the individuals tested. We discuss several
      examples of research questions for which it would be theoretically crucial to
      determine whether manipulations really have no effect at the individual level,
      and we present a method of testing for individual-level effects. (PsycINFO
      Database Record

PMID- 29058942
TI  - The effects of bedtime writing on difficulty falling asleep: A polysomnographic
      study comparing to-do lists and completed activity lists.
AB  - Bedtime worry, including worrying about incomplete future tasks, is a significant
      contributor to difficulty falling asleep. Previous research showed that writing
      about one's worries can help individuals fall asleep. We investigated whether the
      temporal focus of bedtime writing-writing a to-do list versus journaling about
      completed activities-affected sleep onset latency. Fifty-seven healthy young
      adults (18-30) completed a writing assignment for 5 min prior to overnight
      polysomnography recording in a controlled sleep laboratory. They were randomly
      assigned to write about tasks that they needed to remember to complete the next
      few days (to-do list) or about tasks they had completed the previous few days
      (completed list). Participants in the to-do list condition fell asleep
      significantly faster than those in the completed-list condition. The more
      specifically participants wrote their to-do list, the faster they subsequently
      fell asleep, whereas the opposite trend was observed when participants wrote
      about completed activities. Therefore, to facilitate falling asleep, individuals
      may derive benefit from writing a very specific to-do list for 5 min at bedtime
      rather than journaling about completed activities. (PsycINFO Database Record

PMID- 29058943
TI  - A re-examination of "bias" in human randomness perception.
AB  - Human randomness perception is commonly described as biased. This is because when
      generating random sequences humans tend to systematically under- and
      overrepresent certain subsequences relative to the number expected from an
      unbiased random process. In a purely theoretical analysis we have previously
      suggested that common misperceptions of randomness may actually reflect genuine
      aspects of the statistical environment, once cognitive constraints are taken into
      account which impact on how that environment is actually experienced (Hahn &
      Warren, Psychological Review, 2009). In the present study we undertake an
      empirical test of this account, comparing human-generated against unbiased
      process-generated binary sequences in two experiments. We suggest that comparing
      human and theoretically unbiased sequences using metrics reflecting the
      constraints imposed on human experience provides a more meaningful picture of lay
      people's ability to perceive randomness. Finally, we propose a simple generative
      model of human random sequence generation inspired by the Hahn and Warren
      account. Taken together our results question the notion of bias in human
      randomness perception. (PsycINFO Database Record

PMID- 29058944
TI  - Statin drug interactions and related adverse reactions: an update.
AB  - INTRODUCTION: Statins reduce the risk of cardiovascular morbidity and mortality
      in patients with or at risk for cardiovascular disease and their use is
      expanding, especially in elderly. Statins are prescribed on a long-term basis and
      may undergo drug-drug interactions (DDIs) with other drugs. Statins have
      different safety and tolerability, and this might affect the possibility of DDIs
      with other cardiovascular drugs, increasing the risk of statin-associated
      myopathy and hepatotoxicity. Polypharmacy and pharmacogenetic variability are
      potential causes of statin DDIs. Thus, the safety and adverse effects of statins,
      particularly in patients receiving multiple medications at risk of DDIs, are a
      matter of special concern. Areas covered: The purpose of this manuscript is to
      give an update on the potential statin DDIs and related adverse drug reactions
      (myopathy and hepatotoxicity), with special considerations on polypharmacy in
      elderly population, HIV patients, cardiovascular drugs and liver toxicities. The
      potential DDIs among statins and monoclonal antibodies including the recently
      approved PCSK9 inhibitors are also extensively discussed in the present review.
      Expert opinion: A better understanding of the incidence and clinical significance
      of statin DDIs will help physicians in fine-tuning the lipid-lowering therapeutic
      interventions thus providing their patients with an evidence-based, safe and cost
      effective clinical support.

PMID- 29058945
TI  - The Role of Controlled Substance Use in Diversion Outcomes Among Mentally Ill
      Offenders: A Pilot Study.
AB  - Diversion programs offer opportunities to offenders with substance abuse or
      mental illness to attend treatment as an alternative to incarceration. The
      present study identified variables associated with drug relapse and recidivism
      and the moderating role of substance use on recidivism in a diversion sample.
      Data were collected from 80 clients with psychotic disorders from a diversion
      program in New York City. Outcomes were examined after 6 and 12 months of program
      participation. Individuals who used controlled substances other than alcohol or
      cannabis were more likely to have a positive toxicology result than those who
      used alcohol or cannabis only or those with no alcohol/drug history. Individuals
      with schizoaffective disorder were more likely to be rearrested than individuals
      with other diagnoses, as were those with a violent offense (e.g., assault,
      robbery). Positive toxicology results were unrelated to rearrest and did not
      moderate recidivism, suggesting substance abuse may be only indirectly related to
      rearrest among diverted offenders.

PMID- 29058946
TI  - Impact of a novel interprofessional dental and pharmacy student tobacco cessation
      education programme on dental patient outcomes.
AB  - The dental setting presents a unique opportunity to assist patients with tobacco
      cessation. Many dental providers do not feel prepared to provide tobacco
      cessation, particularly with regard to education on pharmacological treatments.
      An interprofessional practice experience with dental and pharmacy students
      provides a novel approach to tobacco cessation in the dental setting, but it is
      not known whether such methods affect patient outcomes. The goal of the study was
      to examine the impact of a novel dental and pharmacy student tobacco cessation
      education programme on patient knowledge gained, barriers to utilising cessation
      medications, quit intentions, and quit behaviours as compared to standard care.
      Dental patients who were seen at the dental admissions clinic of a dental school
      on interprofessional care (IPC) days and received tobacco cessation education
      from the dental-pharmacy student team (N = 25) were compared with dental patients
      at the clinic seen on Standard Care (SC) days (N = 25). Patients completed a post
      appointment survey and a 4-week follow-up survey. IPC patients reported greater
      perceived knowledge post-appointment and at follow-up regarding tobacco cessation
      compared with SC patients and had greater intentions to utilise medication to
      assist with tobacco cessation. At follow-up there were no differences between
      groups in terms of quit attempts. Among patients who made a quit attempt those in
      the IPC group were more likely to have set a quit date and contacted a provider
      for assistance regarding tobacco cessation. Dental-pharmacy student
      interprofessional tobacco cessation may be an innovative way to provide tobacco
      cessation education to dental patients and provide students with
      interprofessional practice experiences.

PMID- 29058947
TI  - The oxidative stability of omega-3 oil-in-water nanoemulsion systems suitable for
      functional food enrichment: A systematic review of the literature.
AB  - There is growing demand for functional food products enriched with long chain
      omega-3 polyunsaturated fatty acids (LComega3PUFA). Nanoemulsions, systems with
      extremely small droplet sizes have been shown to increase LComega3PUFA
      bioavailability. However, nanoemulsion creation and processing methods may impact
      on the oxidative stability of these systems. The present systematic review
      collates information from studies that evaluated the oxidative stability of
      LComega3PUFA nanoemulsions suitable for use in functional foods. The systematic
      search identified seventeen articles published during the last 10 years.
      Researchers used a range of surfactants and antioxidants to create systems which
      were evaluated from 7 to 100 days of storage. Nanoemulsions were created using
      synthetic and natural emulsifiers, with natural sources offering equivalent or
      increased oxidative stability compared to synthetic sources, which is useful as
      consumers are demanding natural, cleaner label food products. Equivalent
      vegetarian sources of LComega3PUFA found in fish oils such as algal oils are
      promising as they provide direct sources without the need for conversion in the
      human metabolic pathway. Quillaja saponin is a promising natural emulsifier that
      can produce nanoemulsion systems with equivalent/increased oxidative stability in
      comparison to other emulsifiers. Further studies to evaluate the oxidative
      stability of quillaja saponin nanoemulsions combined with algal sources of
      LComega3PUFA are warranted.

PMID- 29058948
TI  - PACE study: real-life Psoriasis Area and Severity Index (PASI) 100 response with
      biological agents in moderate-severe psoriasis.
AB  - BACKGROUND: Few studies have compared the use of different biologics in a real
      life setting in plaque psoriasis patients. OBJECTIVE: To compare the efficacy of
      biologics in psoriasis/psoriatic arthritis patients. METHODS: Patients treated
      with adalimumab, etanercept and ustekinumab for at least 16 weeks were included.
      Achievement of Psoriasis Area Severity Index (PASI), PASI 90/100 response and
      time taken to achieve PASI 90/100 response were measured. Logistic regression was
      used to evaluate the effect of psoriasis localization on achievement of PASI 100
      response. RESULTS: Two hundred and fifty five patients were included. No
      difference was observed in PASI 90 response between etanercept and ustekinumab
      (65.5 vs. 55.4%), while adalimumab-treated patients had a higher response
      versusustekinumab (71.6 vs. 55.4%, p = .02). More patients achieved complete
      remission (PASI 100 response) with adalimumab versus etanercept (65.7 vs. 23%, p
      < .001) or ustekinumab (65.7 vs. 44.6%, p = .003). Adalimumab-treated patients
      achieving PASI 90 responded more quickly (by three and six months) versus
      ustekinumab or etanercept. PASI100 response was achieved in ~43% of adalimumab
      and ustekinumab treated-patients by three months versus etanercept (14.3%),
      increasing to 92.5, 85.4 and 35.7%, respectively by six months. PASI100 response
      was associated with psoriasis nail involvement or genital psoriasis. CONCLUSION:
      In the real-life setting, adalimumab was the most effective biological agent for
      the treatment of plaque psoriasis.

PMID- 29058949
TI  - Lipomas of the Brachial Plexus: A Case Series and Review of the Literature.
AB  - BACKGROUND: Lipomas are common benign tumors. When they develop in proximity to
      peripheral nerves, they can cause neurologic symptoms secondary to mass effect.
      Previous reports have shown symptom resolution after removal of lipomas
      compressing various upper extremity peripheral nerves. However, brachial plexus
      lipomas are relatively rare. Our multidisciplinary experience with brachial
      plexus lipoma resection is reviewed in the largest case series to date. METHODS:
      A retrospective chart review of all patients undergoing resection of brachial
      plexus lipomatous tumors between 2006 and 2016 was performed. Patient demographic
      data, diagnostic imaging, clinical presentation, operative details, surgical
      pathology, and clinical outcomes were reviewed. RESULTS: Twelve brachial plexus
      lipomatous tumors were resected in 11 patients: 10 lipomas, 1 hibernoma, and 1
      atypical lipomatous tumor. The most common tumor location was supraclavicular
      (50%), followed by axillary (42%), and proximal medial arm (8%). The most common
      brachial plexus segment involved was the upper trunk (50%), followed by posterior
      cord (25%), lateral pectoral nerve (8%), lower trunk (8%), and proximal median
      nerve (8%). Most patients presented with an enlarging painless mass (58%). Of the
      patients who presented with neurologic symptoms, symptoms resolved in the
      majority (80%). CONCLUSIONS: Brachial plexus lipomas are rare causes of
      compression neuropathy in the upper extremity. Careful resection and knowledge of
      brachial plexus anatomy, which may be distorted by the tumor, are critical to
      achieving a successful surgical outcome with predictable symptom resolution.
      Finally, surveillance magnetic resonance imaging may be warranted for atypical
      lesions.

PMID- 29058950
TI  - Development of a Seating Comfort Questionnaire for Motorcycles.
AB  - Objective The aim of this study is to develop a reliable and valid Motorcycle
      Seating Comfort Questionnaire (MSCQ). Background Motorcycle seat development is
      an iterative process based on subjective evaluations; however, there are no
      established subjective tools for evaluation of seating comfort. Research also
      suggests that seating comfort in motorcycles is poor and needs improvement. The
      development of a MSCQ therefore is an important step that can enable further
      research and aid in improving the design of motorcycle seats. Method The MSCQ is
      developed following guidelines available in literature and referring to
      established questionnaires for seating comfort in passenger cars. The MSCQ is
      further refined based on pilot studies and interviews with experts. The final
      version of the MSCQ is then statistically evaluated for reliability and validity.
      The reliability is evaluated using a test-retest protocol with 31 volunteers. The
      validity is evaluated by comparing the ratings of the MSCQ with that of the
      Category Partitioning Scale (CP50 scale). The validity test is carried out with
      15 volunteers evaluating five motorcycles using both scales. Results The results
      show that the MSCQ is reliable with a significant test-retest reliability
      coefficient ( r = 0.72, p < .01, n = 31) and internal consistency (Cronbach's
      alpha = 0.81, n = 31). The results also show that ratings of the MSCQ have a
      significant correlation ( r = -0.765, p < .05, n = 15) with that of CP50,
      establishing its validity. Conclusions A Motorcycle Seating Comfort Questionnaire
      is developed in this study with statistically established reliability and
      validity. Applications The MSCQ can be used as a tool for evaluation of seating
      comfort in motorcycles. The MSCQ can also form a basis for further research on
      motorcycle seating to develop prediction models and guidelines for the design of
      motorcycle seats.

PMID- 29058951
TI  - Stability of the Syndesmosis After Posterior Malleolar Fracture Fixation.
AB  - BACKGROUND: We sought to define the rate of syndesmotic instability after
      anatomic reduction of the posterior malleolus when posterior stabilization of a
      trimalleolar or trimalleolar equivalent ankle fracture was chosen vs when a
      supine position and initially conservative management of the posterior elements
      was chosen. METHODS: The types of syndesmotic and posterior malleolar fixation
      used to treat adult patients with ankle fractures involving the posterior
      malleolus at our level I trauma center were retrospectively assessed (N = 198).
      Specifically, both bimalleolar and trimalleolar fractures were included.
      Exclusion criteria included pilon fractures, trimalleolar fractures with Chaput
      fragments, and neurologic injury. Demographics, fracture classification, initial
      operative position, medial clear space, and posterior malleolar fragment size
      were recorded for each fracture. RESULTS: In total, 151 patients (76.3%) were
      initially positioned supine, 27.2% of whom had syndesmotic instability requiring
      operative stabilization. Almost 25% of supine patients also underwent posterior
      malleolar stabilization for posterior instability. Overall, 73 (48.3%) patients
      who were initially treated in the supine position needed some form of additional
      stabilization. Forty-seven patients (23.7%) were initially positioned prone.
      Syndesmotic stability was restored in 97.9% of these patients. This 2.1% rate of
      instability vastly differs from the 13-fold higher syndesmotic instability rate
      observed in the supine group ( P < .001). CONCLUSION: Our data demonstrate that
      the rate of syndesmotic instability was reduced in trimalleolar and trimalleolar
      equivalent fractures when prone positioning and direct fixation of the posterior
      malleolus were first performed. Using traditional preoperative estimates of
      posterior stability to determine the need for posterior malleolar fixation may be
      inadequate since almost a quarter of patients treated supine received posterior
      stabilization. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

PMID- 29058954
TI  - Migraine and cognitive function: Baseline findings from the Brazilian
      Longitudinal Study of Adult Health: ELSA-Brasil.
AB  - Background The association between migraine and cognitive performance is unclear.
      We analyzed whether migraine is associated with cognitive performance among
      participants of the Brazilian Longitudinal Study of Adult Health, ELSA-Brasil.
      Methods Cross-sectional analysis, including participants with complete
      information about migraine and aura at baseline. Headache status (no headaches,
      non-migraine headaches, migraine without aura and migraine with aura), based on
      the International Headache Society classification, was used as the dependent
      variable in the multilinear regression models, using the category "no headache"
      as reference. Cognitive performance was measured with the Consortium to Establish
      a Registry for Alzheimer's Disease word list memory test (CERAD-WLMT), the
      semantic fluency test (SFT), and the Trail Making Test version B (TMTB). Z-scores
      for each cognitive test and a composite global score were created and analyzed as
      dependent variables. Multivariate models were adjusted for age, gender,
      education, race, coronary heart disease, heart failure, hypertension, diabetes,
      dyslipidemia, body mass index, smoking, alcohol use, physical activity,
      depression, and anxiety. In women, the models were further adjusted for hormone
      replacement therapy. Results We analyzed 4208 participants. Of these, 19%
      presented migraine without aura and 10.3% presented migraine with aura. All
      migraine headaches were associated with poor cognitive performance (linear
      coefficient beta; 95% CI) at TMTB -0.083 (-0.160; -0.008) and poorer global z
      score -0.077 (-0.152; -0.002). Also, migraine without aura was associated with
      poor cognitive performance at TMTB -0.084 (-0.160, -0.008 and global z-score 
      0.077 (-0.152; -0.002). Conclusion In participants of the ELSA-study, all
      migraine headaches and migraine without aura were significantly and independently
      associated with poorer cognitive performance.

PMID- 29058952
TI  - Increased arterial stiffness in children with congenital heart disease.
AB  - Objective Central systolic blood pressure (SBP) is a measure of arterial
      stiffness and strongly associated with atherosclerosis and end-organ damage. It
      is a stronger predictor of cardiovascular events and all-cause mortality than
      peripheral SBP. In particular, for children with congenital heart disease, a
      higher central SBP might impose a greater threat of cardiac damage. The aim of
      the study was to analyse and compare central SBP in children with congenital
      heart disease and in healthy counterparts. Patients and methods Central SBP was
      measured using an oscillometric method in 417 children (38.9% girls, 13.0 +/- 3.2
      years) with various congenital heart diseases between July 2014 and February
      2017. The test results were compared with a recent healthy reference cohort of
      1466 children (49.5% girls, 12.9 +/- 2.5 years). Results After correction for
      several covariates in a general linear model, central SBP of children with
      congenital heart disease was significantly increased (congenital heart disease:
      102.1 +/- 10.2 vs. healthy reference cohort: 100.4 +/- 8.6, p < .001). The
      analysis of congenital heart disease subgroups revealed higher central SBP in
      children with left heart obstructions (mean difference: 3.6 mmHg, p < .001),
      transpositions of the great arteries after arterial switch (mean difference: 2.2
      mmHg, p = .017) and univentricular hearts after total cavopulmonary connection
      (mean difference: 2.1 mmHg, p = .015) compared with the reference. Conclusion
      Children with congenital heart disease have significantly higher central SBP
      compared with healthy peers, predisposing them to premature heart failure.
      Screening and long-term observations of central SBP in children with congenital
      heart disease seems warranted in order to evaluate the need for treatment.

PMID- 29058955
TI  - MTC Sadism Scale: Toward a Dimensional Assessment of Severe Sexual Sadism With
      Behavioral Markers.
AB  - Sadism was initially described as the experience of sexual pleasure produced by
      acts of cruelty and bodily punishment. Sadism was conceptualized as if sadists
      were fundamentally different from nonsadists. Recent studies have suggested that
      sadism is distributed as a dimension rather than as a category. The aim of the
      current study was to assess the psychometric properties the MTC Sexual Sadism
      Scale. Our analyses were conducted on a sample of 486 sexual offenders assessed
      at a correctional institution in Massachusetts. In summary, the results indicate
      that the MTC Sexual Sadism Scale possesses good psychometric properties for the
      dimensional assessment of severe sexual sadism with behavioral markers. Moreover,
      the scale captures a wide range of intensity of sadism among sexual offenders.
      These results are consistent with prior research and support the current
      consensus to move toward a dimensional interpretation of sadism. Implications
      both for clinical assessment and for research on the development of sadism are
      discussed.

PMID- 29058956
TI  - Assessing Capacity of Faith-Based Organizations for Health Promotion Activities.
AB  - BACKGROUND: Faith-based organizations (FBOs) are important venues for health
      promotion, particularly in medically underserved communities. These organizations
      vary considerably in their structural capacities, which may be linked to
      variability in implementation success for health promotion initiatives. Lacking
      an existing validated assessment of organizational capacity specific to FBOs, an
      initial prototype assessment was developed. METHOD: The Faith-Based Organization
      Capacity Inventory (FBO-CI) assesses three structural areas of capacity: Staffing
      and Space, Health Promotion Experience, and External Collaboration. The
      multidisciplinary team, including FBO leaders, codeveloped the initial
      instrument. The initial reliability from a convenience sample of 34 African
      American churches including descriptions of FBOs representing three capacity
      levels is reported. RESULTS: The FBO-CI demonstrated feasibility of
      administration using an in-person interview format, and the three subscales had
      acceptable internal reliability (alpha ~ .70). Most churches had an established
      health ministry (n = 23) and had conducted activities across an average of seven
      health areas in the previous 2 years. CONCLUSIONS: This initial FBO-CI prototype
      is promising, and future work should consider validation with a larger sample of
      churches and domain expansion based on the conceptual model. The FBO-CI has a
      number of potential uses for researchers, FBO leaders, and practitioners working
      with FBOs in health promotion initiatives.

PMID- 29058958
TI  - Biomarkers in mesothelioma.
AB  - Mesothelioma is an aggressive cancer of pleural and peritoneal cells that is
      difficult to diagnose and monitor. Numerous studies have attempted to identify a
      blood- or pleural fluid-based biomarker that could be used in the diagnostic
      pathway. More recently, there has been interest in the ability of serum/plasma
      biomarkers to monitor mesothelioma, given the development of newer treatments and
      limitations of radiological assessment. The majority of research has focused on
      soluble mesothelin, a soluble glycoprotein expressed by mesothelial cells.
      Although soluble mesothelin lacks the sensitivity to be used as a standalone
      diagnostic marker, serial measurements may be informative, with rising
      concentrations indicating disease progression and poor survival. High
      concentrations of other soluble glycoproteins, such as osteopontin, fibulin-3 and
      vascular endothelial growth factor are independently associated with poor
      prognosis at baseline, although further research is required to ascertain any
      role outside of clinical trials. More recent literature has focused on the
      development of novel biomarkers from discovery cohorts. Although many DNA and
      mRNA biomarkers show promise in the diagnosis or screening of mesothelioma, none
      have been prospectively evaluated for use in clinical practice. In this review
      article, we highlight the potential utility of biomarkers and evaluate the
      existing literature.

PMID- 29058957
TI  - CTGF Is Expressed During Cystic Remodeling in the PKD/Mhm (cy/+) Rat Model for
      Autosomal-Dominant Polycystic Kidney Disease (ADPKD).
AB  - Connective tissue growth factor (CTGF, also named CCN2) plays an important role
      in the development of tubulointerstitial fibrosis, which most critically
      determines the progression to end-stage renal failure in autosomal-dominant
      polycystic kidney disease (ADPKD), the most common genetically caused renal
      disease. We determined CTGF expression in a well-characterized animal model of
      human ADPKD, the PKD/Mhm (cy/+) rat. Kidneys of 12 weeks old (cy/+) as well as
      (+/+) non-affected rats were analyzed for CTGF RNA and protein expression by RT
      PCR, Northern and Western blot analyses, in situ hybridization, and IHC. Besides
      the established expression of CTGF in glomerular cells in kidneys of wild-type
      (+/+) animals, in (cy/+) rats, CTGF mRNA and protein were robustly expressed in
      interstitial, stellate-shaped cells, located in a scattered pattern underlying
      the cystic epithelium and in focal areas of advanced tubulointerstitial
      remodeling. Renal CTGF mRNA and protein expression levels were significantly
      higher in (cy/+) rats compared with their (+/+) littermates. Detection of CTGF
      expression in cells adjacent to cystic epithelium and in areas of marked fibrosis
      suggests a role in the local response to cyst development and indicates that CTGF
      may be a relevant factor contributing to tubulointerstitial fibrosis in
      polycystic kidney disease.

PMID- 29058959
TI  - Impact of economic crisis on the social representation of mental health: Analysis
      of a decade of newspaper coverage.
AB  - BACKGROUND: Mass media plays a fundamental role in how communities understand
      mental health and its treatment. However, the effect of major events such as
      economic crises on the depiction of mental health is still unclear. AIMS: This
      study aimed at analyzing representations of mental health and its treatment and
      the impact of the 2008 economic crisis. METHODS: In total, 1,000 articles were
      randomly selected from two newspapers from a period before and after the economic
      crisis. These articles were analyzed with a closed coding system that classified
      the news as good or bad news according to the presence of themes associated with
      positive or stigmatizing representations. RESULTS: The results show a positive
      representation of mental health and a negative representation of treatment.
      Furthermore, the economic crisis had a negative impact on the representation of
      mental health, but not on treatment. CONCLUSION: These findings suggest that the
      representation of mental health is multifaceted and may be affected differently
      in its dimensions. There is a need for stigma-reducing interventions that both
      account for this complexity and are sensitive to context and period.

PMID- 29058960
TI  - Beneficial and detrimental effects of genetic explanations for addiction.
AB  - BACKGROUND: Addictions are highly stigmatized and increasingly construed as
      biomedical diseases caused by genes, partly to reduce stigma by deflecting blame.
      However, genetic explanations may have negative effects, which have been
      understudied in the context of addiction. How the effects of genetic explanations
      might differ for substance addictions versus behavioral addictions is also
      unknown. AIMS: This study examined the impact of genetic explanations for
      addiction on measures of treatment expectancies, blame, and perceived agency and
      self-control, as well as whether these varied depending on whether the addiction
      was to a substance or a behavior. METHODS: Participants read about a person
      ('Charlie') with either alcohol use disorder or gambling disorder, receiving
      either a genetic or nongenetic explanation of Charlie's problem. They rated how
      much they blamed Charlie for his disorder, his likelihood of benefitting from
      medication or psychotherapy, and how much agency and self-control they ascribed
      to him. RESULTS: Compared to the nongenetic explanation, the genetic explanation
      reduced blame and increased confidence in the effectiveness of pharmacotherapy.
      However, it also decreased the expected effectiveness of psychotherapy and
      reduced ascriptions of agency and self-control. CONCLUSION: Genetic explanations
      for addiction appear to be a 'double-edged sword', with beneficial effects that
      come at a cost.

PMID- 29058961
TI  - "Who Are You From?": The Importance of Family Stories.
AB  - This article emphasizes the importance of family stories, or intergenerational
      narratives, and their health benefits across the lifespan. Knowing and sharing
      the story of who you are from complements the current focus on knowing and
      sharing one's geographic heritage, or where you are from. Knowing one's family
      stories creates meaning that goes beyond the individual to provide a sense of
      self, through time, and in relation to family. This expanded sense of self is
      referred to as our intergenerational self, which not only grounds an individual
      but also provides a larger context for understanding and dealing with life's
      experience(s) and challenges. This connection across generations appears to
      contribute to resilience at all stages of life. This shift in focus challenges
      family nurses to rethink and/or prioritize the use of family stories as a key
      health-promoting intervention for not only children but also their parents, and
      their parents' parents.

PMID- 29058962
TI  - Performance of shear-wave elastography for breast masses using different region
      of-interest (ROI) settings.
AB  - Background Various size and shape of region of interest (ROI) can be applied for
      shear-wave elastography (SWE). Purpose To investigate the diagnostic performance
      of SWE according to ROI settings for breast masses. Material and Methods To
      measure elasticity for 142 lesions, ROIs were set as follows: circular ROIs 1 mm
      (ROI-1), 2 mm (ROI-2), and 3 mm (ROI-3) in diameter placed over the stiffest part
      of the mass; freehand ROIs drawn by tracing the border of mass (ROI-M) and the
      area of peritumoral increased stiffness (ROI-MR); and circular ROIs placed within
      the mass (ROI-C) and to encompass the area of peritumoral increased stiffness
      (ROI-CR). Mean (Emean), maximum (Emax), and standard deviation (ESD) of
      elasticity values and their areas under the receiver operating characteristic
      (ROC) curve (AUCs) for diagnostic performance were compared. Results Means of
      Emean and ESD significantly differed between ROI-1, ROI-2, and ROI-3 ( P <
      0.0001), whereas means of Emax did not ( P = 0.50). For ESD, ROI-1 (0.874) showed
      a lower AUC than ROI-2 (0.964) and ROI-3 (0.975) ( P < 0.002). The mean ESD was
      significantly different between ROI-M and ROI-MR and between ROI-C and ROI-CR ( P
      < 0.0001). The AUCs of ESD in ROI-M and ROI-C were significantly lower than in
      ROI-MR ( P = 0.041 and 0.015) and ROI-CR ( P = 0.007 and 0.004). Conclusion Shear
      wave elasticity values and their diagnostic performance vary based on ROI
      settings and elasticity indices. Emax is recommended for the ROIs over the
      stiffest part of mass and an ROI encompassing the peritumoral area of increased
      stiffness is recommended for elastic heterogeneity of mass.

PMID- 29058963
TI  - Contrast-enhanced spectral mammography in patients with MRI contraindications.
AB  - Background Contrast-enhanced spectral mammography (CESM) is a novel breast
      imaging technique providing comparable diagnostic accuracy to breast magnetic
      resonance imaging (MRI). Purpose To show that CESM in patients with MRI
      contraindications is feasible, accurate, and useful as a problem-solving tool,
      and to highlight its limitations. Material and Methods A total of 118 patients
      with MRI contraindications were examined by CESM. Histology was obtained in 94
      lesions and used as gold standard for diagnostic accuracy calculations. Imaging
      data were reviewed retrospectively for feasibility, accuracy, and technical
      problems. The diagnostic yield of CESM as a problem-solving tool and for therapy
      response evaluation was reviewed separately. Results CESM was more accurate than
      mammography (MG) for lesion categorization (r = 0.731, P < 0.0001 vs. r = 0.279,
      P = 0.006) and for lesion size estimation (r = 0.738 vs. r = 0.689, P < 0.0001).
      Negative predictive value of CESM was significantly higher than of MG (85.71% vs.
      30.77%, P < 0.0001). When used for problem-solving, CESM changed patient
      management in 2/8 (25%) cases. Superposition artifacts and timing problems
      affected diagnostic utility in 3/118 (2.5%) patients. Conclusion CESM is a
      feasible and accurate alternative for patients with MRI contraindications, but it
      is necessary to be aware of the method's technical limitations.

PMID- 29058964
TI  - Short report letter: Combined bilateral carpal coalition of the scaphoid and
      trapezium and of the lunate and triquetrum.

PMID- 29058965
TI  - Congenital longitudinal cleavage of the forearm.

PMID- 29058966
TI  - High-Level Isolation Unit Infection Control Procedures.
AB  - The 2014-2016 Ebola outbreak in West Africa prompted a select group of US
      hospitals to establish high-level isolation units equipped with advanced
      engineering controls, trained staff, and stringent protocols to safely treat
      highly infectious disease patients. This survey details the comprehensive
      infection control protocols developed by these units, including for
      decontamination of units, post-mortem management, liquid waste disposal, and
      personal protective equipment (PPE) use. In spring 2016, a survey was
      electronically distributed to the 56 original Centers for Disease Control and
      Prevention (CDC)-designated high-level isolation units. Responses were collected
      via a fillable PDF and analyzed using descriptive statistics. Thirty-six (64%)
      high-level isolation units responded; 33 completed the survey, and 3 reported
      they no longer maintained high-level isolation unit capabilities. Nearly all
      responding units had written procedures for decontamination, liquid waste
      disposal, and PPE use; however, infection control protocols varied between units.
      High-level isolation units implemented multiple strategies in promoting hand
      hygiene among staff and in monitoring correct PPE use. Maximum time allowed in
      full PPE was restricted in all but 2 units (average of 3.45 hours per shift).
      Almost all (94%) had written procedures for the management of human remains,
      although only 2 units had written protocols for an autopsy of a patient with a
      highly infectious disease. While the vast majority of high-level isolation units
      reported having written protocols for infection control practices, staff
      compliance and procedural application are the true indicators of the state of
      preparedness. Therefore, rigorous training and staff adherence to infection
      control practices is critical to minimizing exposure risks.

PMID- 29058967
TI  - A Public Health Preparedness Logic Model: Assessing Preparedness for Cross-border
      Threats in the European Region.
AB  - Improving preparedness in the European region requires a clear understanding of
      what European Union (EU) member states should be able to do, whether acting
      internally or in cooperation with each other or the EU and other multilateral
      organizations. We have developed a preparedness logic model that specifies the
      aims and objectives of public health preparedness, as well as the response
      capabilities and preparedness capacities needed to achieve them. The
      capabilities, which describe the ability to effectively use capacities to
      identify, characterize, and respond to emergencies, are organized into 5
      categories. The first 3 categories-(1) assessment; (2) policy development,
      adaptation, and implementation; and (3) prevention and treatment services in the
      health sector-represent what the public health system must accomplish to respond
      effectively. The fourth and fifth categories represent a series of interrelated
      functions needed to ensure that the system fulfills its assessment, policy
      development, and prevention and treatment roles: (4) coordination and
      communication regards information sharing within the public health system,
      incident management, and leadership, and (5) emergency risk communication focuses
      on communication with the public. This model provides a framework for identifying
      what to measure in capacity inventories, exercises, critical incident analyses,
      and other approaches to assessing public health emergency preparedness, not how
      to measure them. Focusing on a common set of capacities and capabilities to
      measure allows for comparisons both over time and between member states, which
      can enhance learning and sharing results and help identify both strengths and
      areas for improvement of public health emergency preparedness in the EU.

PMID- 29058968
TI  - Reporting of False Data During Ebola Virus Disease Active Monitoring-New York
      City, January 1, 2015-December 29, 2015.
AB  - The New York City Department of Health and Mental Hygiene (DOHMH) began to
      actively monitor people potentially exposed to Ebola virus on October 25, 2014.
      Active monitoring was critical to the Ebola virus disease (EVD) response and
      mitigated risk without restricting individual liberties. Noncompliance with
      active monitoring procedures has been reported. We conducted a survey of 4,075
      eligible persons to evaluate (1) the frequency of reporting of false data during
      active monitoring, and (2) factors associated with reporting of false temperature
      data. A total of 393 persons (9.6%) responded to the survey. Fifty-five (14.0%)
      provided false temperature data, 5 (1.3%) did not report EVD-like symptoms that
      they had experienced, and 2 (0.5%) did not report a hospital or emergency room
      visit. Having visited Liberia (OR: 3.4, 95% CI: 1.4-7.9), Sierra Leone (OR: 3.4,
      95% CI: 1.6-7.5), or multiple EVD-affected countries (OR: 12.9, 95% CI: 3.5
      47.7); being aged <50 years (OR: 7.5, 95% CI: 1.7-33.1); and rating the
      importance of active monitoring as low (OR: 1.4, 95% CI: 1.1-1.8) were associated
      with increased odds of reporting false temperature data. Over 10% of respondents
      reported providing false data during EVD active monitoring. However, it remains
      unclear whether reporting of false data during active monitoring impedes the
      ability to rapidly identify EVD cases in settings with a low burden of EVD.

PMID- 29058969
TI  - Public Health and the Pope's Visit to Philadelphia, 2015.
AB  - Pope Francis visited Philadelphia for 2 days during September 2015. Preparedness
      functions managed by the Philadelphia Department of Public Health (PDPH) were
      similar to those of other mass gatherings but also required accommodation of
      special security arrangements and the location of public events in central areas
      of the city. Public health planning involved collaborations with multiple city,
      state, and federal agencies and neighboring jurisdictions. PDPH preparations
      encompassed incident command procedures, contingency planning, disease
      surveillance and prevention, food safety, vector control, BioWatch air sampling,
      volunteer management for first-aid services, and continuity of operations. These
      were based on, or informed by, existing emergency plans and prior experiences in
      responding to public health crises, supporting large public events, managing
      regional preparedness exercises, engaging Medical Reserve Corps volunteers, and
      executing routine functions. Although the papal visit concluded without the
      occurrence of a substantial public health or healthcare emergency, lessons
      learned have and will continue to improve coordination with partner agencies in
      planning and executing large-scale events, as well as managing regional disease
      surveillance procedures and medical volunteer engagement. Another area identified
      for improvement concerns enhancing the role of local health departments in
      planning for responses to possible BioWatch alerts.

PMID- 29058970
TI  - Cerebrospinal fluid drainage and thoracic endovascular aneurysm repair.
AB  - Spinal cord complications including paraplegia and partial neurologic deficits
      remain a frequent problem during repair of descending thoracic or
      thoracoabdominal aortic aneurysms. Effective prevention of this dreaded
      complication is of paramount importance. Among the many adjuncts that have been
      proposed to prevent spinal cord complications, spinal fluid drainage is one that
      has been used by numerous teams. The aim of this review is to answer the
      following question: does spinal fluid drainage afford spinal cord protection
      during both open and endovascular repair of thoracic or thoracoabdominal aortic
      aneurysms?

PMID- 29058971
TI  - Retraction notice.

PMID- 29058972
TI  - Retraction notice.

PMID- 29058973
TI  - Post-recurrence survival analysis of stage I non-small-cell lung cancer.
AB  - Background The aim of this retrospective study was to review recurrence patterns
      of stage I non-small-cell lung cancer and identify prognostic factors for post
      recurrence survival. Methods Among 940 patients with pathological stage I non
      small-cell lung cancer who underwent curative resection, 261 experienced a
      recurrence; of these, 188 had adenocarcinoma and 62 had squamous cell carcinoma.
      Oligo-recurrence was defined as 1-3 recurrent lesions restricted to a single
      organ. Potentially curative local treatment included surgery, stereotactic
      radiotherapy, and photodynamic therapy. Results The median follow-up duration was
      65 months (range 4-186 months). The most common site of recurrence was the lung
      in 145 patients, followed by mediastinal lymph nodes in 49, pleura in 30, and
      brain in 27. Local treatment for recurrent tumors included surgery in 59
      patients, stereotactic radiotherapy in 46, photodynamic therapy in 2, and other
      radiotherapy in 41. Seventy-eight patients received chemotherapy only, and 35
      received conservative treatment. Among 125 patients who were evaluated for an
      epidermal growth factor receptor gene mutation, 31 were treated with epidermal
      growth factor receptor-tyrosine kinase inhibitor. The 3- and 5-year post
      recurrence survival rates were 49.1% and 33.8%, respectively. Age at recurrence,
      adenocarcinoma cell type, disease-free interval, epidermal growth factor receptor
      tyrosine kinase inhibitor treatment, and potentially curative local treatment
      were independent prognostic factors for survival in multivariate analysis.
      Conclusions Local treatment for recurrence should be considered in selected
      candidates, and use of epidermal growth factor receptor-tyrosine kinase inhibitor
      I is reasonable if an epidermal growth factor receptor mutation is detected.

PMID- 29058974
TI  - Inflammatory myofibroblastic tumor of heart in a 4-month-old infant.
AB  - Primary tumors of heart are rare in infants. We report a case of inflammatory
      myofibroblastic tumor in a 4-month-old baby girl who presented with a massive
      pericardial effusion. She underwent complete surgical excision of the tumor. This
      is the first reported case from the Middle Eastern region. The clinical behavior
      and management of these rare infantile cardiac tumors are discussed briefly in
      this report.

PMID- 29058975
TI  - True congenital atresia of the left main coronary ostium: delayed presentation.
AB  - Congenital atresia of the left main coronary ostium is a rare coronary anomaly
      presenting in adulthood. A 48-year-old man presented with unstable angina.
      Coronary angiography showed an absent left coronary ostium with a super-dominant
      right coronary artery retrogradely filling the left system. Computed tomography
      angiography with 3-dimensional reconstruction confirmed the absence of the left
      main coronary artery. In view of ongoing chest pain, the patient was offered
      coronary artery bypass surgery. Total arterial revascularization was performed
      with a left internal mammary artery-left radial artery Y-graft.

PMID- 29058976
TI  - Alien Invasion: Biology of Philornis Flies Highlighting Philornis downsi, an
      Introduced Parasite of Galapagos Birds.
AB  - The muscid genus Philornis comprises approximately 50 described species of flies,
      nearly all of which are obligate parasites of nestling birds. Philornis species
      are native to the Neotropics and widely distributed from Florida to Argentina.
      Most research on this group has focused on P. downsi, which was introduced to the
      Galapagos Islands in the late twentieth century. Although Philornis parasitism
      kills nestlings in several native host species, nowhere do the effects seem more
      severe than in P. downsi in the Galapagos. Here, we review studies of native and
      introduced Philornis in an attempt to identify factors that may influence
      virulence and consider implications for the conservation of hosts in the
      Galapagos.

PMID- 29058977
TI  - Management of Western North American Bark Beetles with Semiochemicals.
AB  - We summarize the status of semiochemical-based management of the major bark
      beetle species in western North America. The conifer forests of this region have
      a long history of profound impacts by phloem-feeding bark beetles, and species
      such as the mountain pine beetle (Dendroctonus ponderosae) and the spruce beetle
      (D. rufipennis) have recently undergone epic outbreaks linked to changing
      climate. At the same time, great strides are being made in the application of
      semiochemicals to the integrated pest management of bark beetles. In this review,
      we synthesize and interpret these recent advances in applied chemical ecology of
      bark beetles for scientists and land managers.

PMID- 29058978
TI  - Advances in Attract-and-Kill for Agricultural Pests: Beyond Pheromones.
AB  - Attract-and-kill has considerable potential as a tactic in integrated management
      of pests of agricultural crops, but the use of sex pheromones as attractants is
      limited by male multiple mating and immigration of mated females into treated
      areas. Attractants for both sexes, and particularly females, would minimize these
      difficulties. Volatile compounds derived from plants or fermentation of plant
      products can attract females and have been used in traps for monitoring and
      control, and in sprayable attract-and-kill formulations or bait stations. Recent
      advances in fundamental understanding of insect responses to plant volatiles
      should contribute to the development of products that can help manage a wide
      range of pests with few impacts on nontarget organisms, but theory must be
      tempered with pragmatism in the selection of volatiles and toxicants and in
      defining their roles in formulations. Market requirements and regulatory factors
      must be considered in parallel with scientific constraints if successful products
      are to be developed.

PMID- 29058979
TI  - Systematics, Biology, and Evolution of Microgastrine Parasitoid Wasps.
AB  - The braconid parasitoid wasp subfamily Microgastrinae is perhaps the most species
      rich subfamily of animals on Earth. Despite their small size, they are familiar
      to agriculturalists and field ecologists alike as one of the principal groups of
      natural enemies of caterpillars feeding on plants. Their abundance and nearly
      ubiquitous terrestrial distribution, their intricate interactions with host
      insects, and their historical association with mutualistic polydnaviruses have
      all contributed to Microgastrinae becoming a key group of organisms for studying
      parasitism, parasitoid genomics, and mating biology. However, these rich sources
      of data have not yet led to a robust genus-level classification of the group, and
      some taxonomic confusion persists as a result. We present the current status of
      understanding of the general biology, taxonomic history, diversity, geographical
      patterns, host relationships, and phylogeny of Microgastrinae as a stimulus and
      foundation for further study. Current progress in elucidating the biology and
      taxonomy of this important group is rapid and promises a revolution in the
      classification of these wasps in the near future.

PMID- 29058980
TI  - Regulatory Pathways Controlling Female Insect Reproduction.
AB  - The synthesis of vitellogenin and its uptake by maturing oocytes during egg
      maturation are essential for successful female reproduction. These events are
      regulated by the juvenile hormones and ecdysteroids and by the nutritional
      signaling pathway regulated by neuropeptides. Juvenile hormones act as
      gonadotropins, regulating vitellogenesis in most insects, but ecdysteroids
      control this process in Diptera and some Hymenoptera and Lepidoptera. The complex
      crosstalk between the juvenile hormones, ecdysteroids, and nutritional signaling
      pathways differs distinctly depending on the reproductive strategies adopted by
      various insects. Molecular studies within the past decade have revealed much
      about the relationships among, and the role of, these pathways with respect to
      regulation of insect reproduction. Here, we review the role of juvenile hormones,
      ecdysteroids, and nutritional signaling, along with that of microRNAs, in
      regulating female insect reproduction at the molecular level.

PMID- 29058981
TI  - Entomological Collections in the Age of Big Data.
AB  - With a million described species and more than half a billion preserved
      specimens, the large scale of insect collections is unequaled by those of any
      other group. Advances in genomics, collection digitization, and imaging have
      begun to more fully harness the power that such large data stores can provide.
      These new approaches and technologies have transformed how entomological
      collections are managed and utilized. While genomic research has fundamentally
      changed the way many specimens are collected and curated, advances in technology
      have shown promise for extracting sequence data from the vast holdings already in
      museums. Efforts to mainstream specimen digitization have taken root and have
      accelerated traditional taxonomic studies as well as distribution modeling and
      global change research. Emerging imaging technologies such as microcomputed
      tomography and confocal laser scanning microscopy are changing how morphology can
      be investigated. This review provides an overview of how the realization of big
      data has transformed our field and what may lie in store.

PMID- 29058982
TI  - A comparative study of negative life events and depressive symptoms among healthy
      older adults and older adults with chronic disease.
AB  - OBJECTIVE: This study aims to study internal relations and functionary mechanism
      between social support, coping style, negative life events and depressive
      symptoms and compare these relations in healthy older adults and older adults
      with chronic disease. DESIGN: A cross-sectional study was conducted in 2015. In
      total, 1,264 older adults with chronic disease and 749 healthy older adults
      participated in this investigation which consist of socio-demographic characters,
      negative life events, social support, coping style and depressive symptoms.
      RESULTS: The path and direction of variable function in healthy older adults were
      inconsistent with older adults with chronic disease. Older adults with chronic
      disease had more severe depressive symptoms and negative life events, and lower
      social support and positive coping style. Negative life events, subjective
      support, positive coping style and negative coping style were significantly
      predicted depressive symptoms. Objective support may weaken the influence of
      negative life events on depressive symptoms in chronic disease group. Utilization
      of support and positive coping style worsen the effect of negative life events on
      depressive symptoms in healthy older adults. CONCLUSION: This study implied that
      to improve their mental health, attention should be paid to the role of
      biological, psychological and social stress factors and its inherent law of
      interaction.

PMID- 29058983
TI  - Participant characteristics in autism intervention studies.
AB  - The purpose of this Letter to the Editor is to discuss the recent paper, "Lessons
      learned: Engaging culturally diverse families in neurodevelopmental disorders
      intervention research" by Ratto et al. Specifically, we are interested in further
      exploring the question of "who participates in autism spectrum disorder
      intervention research," and how this question may impact interpretation of Ratto
      and colleagues' paper.

PMID- 29058984
TI  - Impact of histological thrombus composition on preinterventional thrombus
      migration in patients with acute occlusions of the middle cerebral artery.
AB  - Purpose The occurrence of thrombus migration (TM) in middle cerebral arteries
      (MCAs) prior to mechanical thrombectomy (MT) in patients suffering from acute
      ischemic strokes is a crucial aspect as TM is associated with lower rates of
      complete reperfusion and worse clinical outcomes. In this study, we sought to
      clarify whether histological thrombus composition influences TM. Methods We
      included 64 patients with acute MCA occlusions who had undergone MT. In 11 of the
      cases (17.2%) we identified TM prior to the interventions. The extracted clots
      were collected and histologically examined. The hematoxylin and eosin-stained
      specimens were quantitatively analyzed in terms of the relative fractions of the
      main constituents (red and white blood cells and fibrin/platelets). The
      histologic patterns were correlated with the occurrence of TM. Results Patients
      in whom TM could be observed were more often treated in a drip-and-ship fashion
      (90.9% vs 41.5%, p = 0.003). Stroke etiology did not differ between migrated and
      stable thrombi. A weak tendency for higher RBC and lower F/P content could be
      observed in thrombi that had migrated when compared with stable thrombi (RBC:
      median 41% vs 37%, p = 0.022 and F/P: median 54% vs 57%, p = 0.024). When using a
      cut-off of 60% RBC content for the definition of RBC-rich thrombi, a higher
      portion of RBC-rich thrombi could be identified in the migrated group as opposed
      to the stable group (36.4% vs 5.7%, p = 0.003). Conclusion Preinterventional TM
      may be influenced by the histological thrombus composition in a way that RBC-rich
      thrombi are more prone to migrate.

PMID- 29058985
TI  - Seven years' follow-up of comparative study between stenting and medication for
      treatment of symptomatic vertebrobasilar artery stenosis.
AB  - Objective Endovascular stent-assistant angioplasty (ESAA) is a valid treatment
      for symptomatic vertebrobasilar artery stenosis (SVAS), but the long-term effect
      and the improvement of condition compared with medication treatment are unknown.
      This study investigated the long-term efficacy of ESAA in patients with moderate
      and severe SVAS, and compared the efficacy with medication treatment. Materials
      and methods We conducted a retrospective analysis of clinical data of 43 patients
      with moderate and severe SVAS hospitalized in our department. According to
      different treatment methods they were divided into 29 cases in an ESAA group and
      14 cases in a medication treatment group. During the follow-up period, the degree
      of vascular stenosis, vascular blood flow velocity, restenosis rate, recovery of
      neurological function and the incidence of cerebral ischemic events in the two
      groups were analyzed. Results The average clinical follow-up period was 89.4 +/-
      10.2 months. Before treatment, the stenosis rate and average blood flow velocity
      of the two groups were not statistically significant ( p > 0.05). During the
      follow-up period, both were significantly lower than the medication treatment
      group ( p < 0.01). In the ESAA group, three cases of stent stenosis, and three
      cases in the medication treatment group were completely occluded. The total
      ischemic events in ESAA group were three cases, compared with nine cases in the
      medication treatment group; the difference was statistically significant ( p <
      0.05). Conclusion ESAA has a long-term effect in the treatment of symptomatic
      moderate and severe vertebrobasilar artery stenosis. It is superior to medication
      therapy in preventing posterior circulation ischemia (PCI), but a larger sample
      size is still needed to confirm the study.

PMID- 29058987
TI  - Association between intraoperative blood product transfusions and acute kidney
      injury following cardiac surgery.

PMID- 29058986
TI  - Identification of Clinical and Biologic Correlates Associated With Outcome in
      Children With Adrenocortical Tumors Without Germline TP53 Mutations: A St Jude
      Adrenocortical Tumor Registry and Children's Oncology Group Study.
AB  - Purpose The clinical features, pathogenesis, and outcomes in children with
      adrenocortical tumors (ACTs) without germline TP53 mutations have not been
      systematically studied. Herein, we describe these correlates and analyze their
      association with outcome. Patients and Methods Genomic DNA was analyzed for TP53,
      CTNNB1, CDKN1C, ATRX, and chromosome 11p15 abnormalities. beta-catenin expression
      and Ki-67 labeling index (LI) were evaluated by immunostaining. Primary end
      points were progression-free (PFS) and overall survival. Results Median age of 42
      girls and 18 boys was 3.3 years (range, 0.25 to 21.7 years). Complete resection
      (stages I and II) was achieved in 32 patients, and 28 patients had stage III or
      IV disease. Constitutional abnormalities of chromosome 11p15 occurred in nine of
      40 patients, with six patients not showing phenotype of Beckwith-Wiedemann
      syndrome. Three-year PFS and overall survival for all patients were 71.4% and
      80.5%, respectively. In single-predictor Cox regression analysis, age, disease
      stage, tumor weight, somatic TP53 mutations, and Ki-67 LI were associated with
      prognosis. Ki-67 LI and age remained significantly associated with PFS after
      adjusting for stage and tumor weight. Three-year PFS for 27 patients with Ki-67
      LI >= 15% was 48.5% compared with 96.2% for 29 patients with Ki-67 LI < 15% (log
      rank P = .002), and the rate of relapse increased by 24% with each 1-year
      increase in age at diagnosis (hazard ratio, 1.24; P = .0057). Conclusion
      Clinicopathologic features and outcomes of children with ACTs without germline
      TP53 mutations overlapped those reported for children with germline TP53
      mutations. Our findings highlight the central role of genetic or epigenetic
      alterations on chromosome 11p15 in pediatric ACTs. Ki-67 LI is a strong
      prognostic indicator and should be investigated to improve the histologic
      classification of pediatric ACTs.

PMID- 29058988
TI  - Understanding "understanding" in Public Understanding of Science.
AB  - This study examines the conflation of terms such as "knowledge" and
      "understanding" in peer-reviewed literature, and tests the hypothesis that little
      current research clearly distinguishes between importantly distinct epistemic
      states. Two sets of data are presented from papers published in the journal
      Public Understanding of Science. In the first set, the digital text analysis
      tool, Voyant, is used to analyze all papers published in 2014 for the use of
      epistemic success terms. In the second set of data, all papers published in
      Public Understanding of Science from 2010-2015 are systematically analyzed to
      identify instances in which epistemic states are empirically measured. The
      results indicate that epistemic success terms are inconsistently defined, and
      that measurement of understanding, in particular, is rarely achieved in public
      understanding of science studies. We suggest that more diligent attention to
      measuring understanding, as opposed to mere knowledge, will increase efficacy of
      scientific outreach and communication efforts.

PMID- 29058989
TI  - Unstressed Vowel Reduction Across Majorcan Catalan Dialects: Production and
      Spoken Word Recognition.
AB  - This study investigates the production and auditory lexical processing of words
      involved in a patterned phonological alternation in two dialects of Catalan
      spoken on the island of Majorca, Spain. One of these dialects, that of Palma,
      merges /o/ and /o/ as [o] in unstressed position, and it maintains /u/ as an
      independent category, [u]. In the dialect of Soller, a small village, speakers
      merge unstressed /o/, /o/, and /u/ to [u]. First, a production study asks whether
      the discrete, rule-based descriptions of the vowel alternations provided in the
      dialectological literature are able to account adequately for these processes:
      are mergers complete? Results show that mergers are complete with regards to the
      main acoustic cue to these vowel contrasts, that is, F1. However, minor
      differences are maintained for F2 and vowel duration. Second, a lexical decision
      task using cross-modal priming investigates the strength with which words
      produced in the phonetic form of the neighboring (versus one's own) dialect
      activate the listeners' lexical representations during spoken word recognition:
      are words within and across dialects accessed efficiently? The study finds that
      listeners from one of these dialects, Soller, process their own and the
      neighboring forms equally efficiently, while listeners from the other one, Palma,
      process their own forms more efficiently than those of the neighboring dialect.
      This study has implications for our understanding of the role of lifelong
      linguistic experience on speech performance.

PMID- 29058990
TI  - Introduction to the Theme "New Approaches for Studying Drug and Toxicant Action:
      Applications to Drug Discovery and Development".
AB  - The theme "New Approaches for Studying Drug and Toxicant Action: Applications to
      Drug Discovery and Development" links 13 articles in this volume of the Annual
      Review of Pharmacology and Toxicology (ARPT). The engaging prefatory articles by
      Arthur Cho and Robert Lefkowitz set the stage for this theme and for the reviews
      that insightfully describe new approaches that advance research and discovery in
      pharmacology and toxicology. Examples include the progress being made in
      developing Organs-on-Chips/microphysiological systems and human induced
      pluripotent stem cell-derived cells to aid in understanding cell and tissue
      pharmacokinetics, action, and toxicity; the recognition of the importance of
      circadian rhythm, the microbiome, and epigenetics in drug and toxicant responses;
      and the application of results from new types of patient-derived information to
      create personalized/precision medicine, including therapeutics for pain, which
      may perhaps provide help in dealing with the opioid epidemic in the United
      States. Such new information energizes discovery efforts in pharmacology and
      toxicology that seek to improve the efficacy and safety of drugs in patients and
      to minimize the consequences of exposure to toxins.

PMID- 29058991
TI  - The involvement of galectin-3 in skin injury in systemic lupus erythematosus
      patients.
AB  - Objective Our previous research suggested that anti-galectin-3 antibody was
      highly associated with the development of lupus skin lesions in systemic lupus
      erythematosus (SLE). In this study we aimed to investigate the involvement of
      galectin-3 in SLE skin damage. Methods The study consisted of 49 patients with
      SLE, 16 with dermatomyositis and 11 with systemic scleroderma and 20 healthy
      controls. Galectin-3 was examined by ELISA and immunohistochemical staining in
      serum and skin, respectively. Results Serum galectin-3 was significantly higher
      in patients with SLE than in those with dermatomyositis ( P < 0.01), systemic
      scleroderma ( P < 0.001) and healthy controls ( P < 0.001); however, it was
      comparable between SLE patients with and without skin lesions ( P = 0.2010 and
      was not correlated with cutaneous disease activity ( r = -0.020, P = 0.93) or
      damage score ( r = -0.380, P = 0.09). Galectin-3 expression was reduced in
      epidermis in lesional skin from patients with SLE, dermatomyositis and systemic
      scleroderma compared to healthy controls ( P = 0.0055), whereas it was comparable
      among diseases ( P > 0.05). As for subtypes of skin lesions in SLE, galectin-3
      expression was lower in chronic cutaneous lupus erythematosus than in acute
      cutaneous lupus erythematosus ( P = 0.0439). Conclusion Serum galectin-3 is
      unlikely to play a role in the pathogenesis of lupus skin damage, but can be a
      potential biomarker for the measurement of SLE disease activity. Galectin-3 is
      greatly reduced in patients with lupus lesions compared with healthy controls,
      which may contribute to the recruitment of inflammatory cells in the skin.

PMID- 29058992
TI  - ANCA in lupus nephritis.

PMID- 29058993
TI  - Neutrophilic urticarial dermatosis and Sweet-like neutrophilic dermatosis: under
      recognized neutrophilic dermatoses in lupus erythematosus.
AB  - Background/Objectives Neutrophilic dermatoses can be associated with autoimmune
      connective tissue diseases such as systemic lupus erythematosus (SLE). We
      analyzed clinical and histological features of neutrophilic urticarial dermatosis
      (NUD) and Sweet-like neutrophilic dermatosis (SLND)-the most recently delineated
      entities of the neutrophilic dermatoses. Methods We retrieved database medical
      records of patients with SLE whose skin biopsy demonstrated a neutrophilic
      predominant infiltrate of the skin, and included those whose biopsies revealed
      findings of SLND or NUD. Results SLND skin lesions lasted longer than those of
      NUD and were localized to sun-exposed areas. All NUD cases resolved within one
      week either spontaneously or with treatment such as antihistamines, but SLND skin
      lesions lasted longer than one week; prednisone was used in four of these five
      patients. All NUD cases were found in existing SLE patients and were not
      associated with systemic signs of flare-up of SLE. However, 80% of SLND cases
      experienced flare-up of SLE; and in 60%, SLND developed concomitantly with SLE as
      a presenting sign. Conclusion Different clinical courses and relationships with
      SLE suggest that NUD and SLND have different pathogeneses for neutrophilic
      inflammatory reactions.

PMID- 29058994
TI  - The optic nerve should be included as one of the typical CNS regions for
      establishing dissemination in space when diagnosing MS - Commentary.

PMID- 29058995
TI  - Regulation of autophagy through SnRK1 and TOR signaling pathways.
AB  - Autophagy is important for degradation and recycling of cytoplasmic materials in
      all eukaryotes and is often triggered by environmental stress. How autophagy is
      activated in plants under different environmental conditions is still poorly
      understood. Our recent studies show that induction of autophagy by different
      abiotic stress conditions can occur via either a TOR-dependent or -independent
      pathway, depending on the stress. The SnRK1 protein kinase complex acts upstream
      of TOR in regulation of autophagy during nutrient deficiency, salt and osmotic
      stresses. In contrast, oxidative and ER stress regulate autophagy in a SnRK1
      dependent but TOR-independent manner. Here we summarize and discuss these
      distinct pathways for activation of autophagy under different environmental
      stress conditions.

PMID- 29058996
TI  - Successful use of extracorporeal membrane oxygenation in a child with obstructive
      shock due to massive bilateral pulmonary embolism.
AB  - BACKGROUND: Acute massive pulmonary embolism (PE) is a very rare condition in
      children. We report the successful use of veno-arterial extracorporeal membrane
      oxygenation (VA ECMO) as a lifesaving modality in a child with acute massive PE.
      CASE PRESENTATION: A nine-year-old female with spinal muscular atrophy type 1,
      chronic respiratory failure with tracheostomy and ventilator dependence presented
      with tachypnea and hypoxia. She had recent coiling of her pulmonary arterio
      venous malformation. A chest computerized tomography scan showed massive
      bilateral PE. Urgent catheter-directed thrombolysis failed. She was placed on VA
      ECMO with stabilization of hemodynamics. She underwent surgical thrombo
      embolectomy followed by weaning of ECMO support. DISCUSSION: The use of VA ECMO
      supported the cardio-respiratory status and perfusion to facilitate surgical
      embolectomy.

PMID- 29058997
TI  - Nonalcoholic Steatohepatitis (NASH) and Hepatic Fibrosis: Emerging Therapies.
AB  - Nonalcoholic fatty liver disease remains a major cause of liver-related morbidity
      and mortality worldwide. It is a complex disease associated with obesity,
      diabetes, and dyslipidemia but is increasingly recognized in normal-weight
      individuals. Its progressive inflammatory phenotype, nonalcoholic steatohepatitis
      (NASH), currently has no effective treatment apart from lifestyle interventions.
      Multiple pathogenic pathways are involved in disease progression, and targets for
      intervention have been identified. These targets mediate glucose, lipid, and bile
      acid metabolism; inflammation; apoptosis; and fibrosis. Novel therapeutic agents
      are being developed in each of these pathways, and several have shown promise in
      early phase testing. Given the complexity of the disease, intervention trials are
      large and long and require histologic confirmation as a primary endpoint for
      disease improvement or regression. We highlight active Phase 2 and 3 therapeutic
      trials for NASH as this field rapidly expands in development.

PMID- 29058998
TI  - Liquid chromatography tandem-mass spectrometry (LC-MS/MS) and dried blood spot
      sampling applied to pharmacokinetics studies in animals: Correlation of classic
      and block design.
AB  - A relative bioavailability study (RBA) of two phenytoin (PHT) formulations was
      conducted in rabbits, in order to compare the results obtained from different
      matrices (plasma and blood from dried blood spot (DBS) sampling) and different
      experimental designs (classic and block). The method was developed by liquid
      chromatography tandem-mass spectrometry (LC-MS/MS) in plasma and blood samples.
      The different sample preparation techniques, plasma protein precipitation and
      DBS, were validated according to international requirements. The analytical
      method was validated with ranges 0.20-50.80 and 0.12-20.32 ug ml-1, r > 0.999 for
      plasma and blood, respectively. Accuracy and precision were within acceptance
      criteria for bioanalytical assay validation (< 15 for bias and CV% and < 20 for
      limit of quantification (LOQ)). PHT showed long-term stability, both for plasma
      and blood, and under refrigerated and room temperature conditions. Haematocrit
      values were measured during the validation process and RBA study. Finally, the
      pharmacokinetic parameters (Cmax, Tmax and AUC0-t) obtained from the RBA study
      were tested. Results were highly comparable for matrices and experimental
      designs. A matrix correlation higher than 0.975 and a ratio of (PHT blood) =
      1.158 (PHT plasma) were obtained. The results obtained herein show that the use
      of classic experimental design and DBS sampling for animal pharmacokinetic
      studies should be encouraged as they could help to prevent the use of a large
      number of animals and also animal euthanasia. Finally, the combination of DBS
      sampling with LC-MS/MS technology showed to be an excellent tool not only for
      therapeutic drug monitoring but also for RBA studies.

PMID- 29058999
TI  - Feasibility of transthoracic echocardiographic imaging in non-sedated ovine
      subjects using a commercial restraint device.
AB  - Transthoracic echocardiography (TTE) is a valuable non-invasive imaging research
      technique. In ovine models of cardiac disease, restraint for TTE often involves
      sedation even with currently available restraint equipment; our goal was to
      determine the feasibility of using a commercial restraint device, commonly known
      as the sheep chair, in minimizing animal stress and the need for sedation while
      achieving a complete TTE examination. A total of 10 healthy adult Dorset sheep
      were restrained in a sheep chair for TTE and observed for signs of stress. No
      animals displayed overt evidence of stress and none required sedation. While
      individual anatomic variation existed, image quality was sufficient to determine
      cardiac function. These observations suggest that a sheep chair is a useful aid
      in minimizing the need for sedation to acquire a full TTE study in ovine
      subjects.

PMID- 29059000
TI  - The optic nerve should be included as one of the typical CNS regions for
      establishing dissemination in space when diagnosing MS - No.

PMID- 29059001
TI  - Activation of the TRPV1 Thermoreceptor Induced by Modulated or Unmodulated 1800
      MHz Radiofrequency Field Exposure.
AB  - The existence of effects of radiofrequency field exposure at environmental levels
      on living tissues and organisms remains controversial, in particular regarding
      potential "nonthermal" effects produced in the absence of temperature elevation.
      Therefore, we investigated whether TRPV1, one of the most studied thermosensitive
      channels, can be activated by the heat produced by radiofrequency fields and by
      some specific nonthermal interaction with the fields. We have recently shown that
      TRPV1 activation can be assessed in real-time on live cells using the
      bioluminescence resonance energy transfer technique. Taking advantage of this
      innovative assay, we monitored TRPV1 thermal and chemical modes of activation
      under radiofrequency exposure at 1800 MHz using different signals (CW, GSM, UMTS,
      LTE, Wi-Fi and WiMAX) at specific absorption rates between 8 and 32 W/kg. We
      showed that, as expected, TRPV1 channels were activated by the heat produced by
      radiofrequency field exposure of transiently-transfected HEK293T cells, but found
      no evidence of TRPV1 activation in the absence of temperature elevation under
      radiofrequency field exposure. There was no evidence either that, at fixed
      temperature, radiofrequency exposure altered the maximal efficacy of the agonist
      Capsaicin to activate TRPV1.

PMID- 29059003
TI  - The optic nerve should be included as one of the typical CNS regions for
      establishing dissemination in space when diagnosing MS - Yes.

PMID- 29059002
TI  - Deactivation of cisplatin-resistant human lung/ovary cancer cells with
      pyropheophorbide-alpha methyl ester-photodynamic therapy.
AB  - The aim of this study was to determine whether photodynamic therapy (PDT) alone
      or combined with cisplatin (DDP), can deactivate cisplatin-resistant cancer
      cells. Human cancer cell lines A549 and SKOV3, and chemoresistant sublines
      A549/DDP and SKOV3/DDP, were subjected to PDT, DDP, or PDT combined with DDP.
      Cell viability and apoptosis were analyzed, and then intracellular reactive
      oxygen species (ROS) and proteins related to apoptosis were determined. PDT
      caused cell death, and PDT combined with DDP led to the highest percentage of
      dead cells in 4 cell lines; similar results were detected in ROS; a
      quantification evaluation manifested that the combined effect was addition. DDP
      increased the percentage of apoptotic cells, and the ROS level in A549 and SKOV3
      cells, which was not observed in A549/DDP and SKOV3/DDP cells. Western blot
      revealed an increase of caspase 3 and Bax, and a decrease of Bcl-2, demonstrating
      the occurrence of apoptosis. The data suggest that PDT can efficiently deactivate
      resistant cells and enhance the action of DDP against resistant cancer cells.

PMID- 29059004
TI  - The appropriateness of the use of influenza vaccines: Recommendations from the
      latest seasons in Italy.
AB  - Influenza is one of the major infectious causes of excess mortality,
      hospitalization, and an increase in healthcare expenditure in all countries. In
      an increasingly ageing population, many members are exposed to flu-related
      complications. Vaccination coverage rates for the elderly in most European
      countries, such as Italy, are not satisfactory, and have been decreasing with
      time due to a sense of skepticism toward vaccination. Nowadays, many types of
      vaccines are available on the Italian market to prevent influenza illness. Many
      studies have proven their effectiveness in preventing influenza-related
      complications in specific risk groups. Any vaccine can be crucial to avoid
      complications, hospitalizations and death, but use of the most appropriate
      vaccine could optimize the result at a very modest cost. General practitioners
      (GPs) should encourage their patients to take the influenza vaccination to
      prevent complications or deaths. Health authorities should give GPs the
      opportunity to choose the appropriate vaccines tailored to specific patients.

PMID- 29059005
TI  - A hand-held robotic device for peripheral intravenous catheterization.
AB  - Intravenous catheterization is frequently required for numerous medical
      treatments. However, this process is characterized by a high failure rate,
      especially when performed on difficult patients such as newborns and infants.
      Very young patients have small veins, and that increases the chances of
      accidentally puncturing the catheterization needle directly through them. In this
      article, we present the design, development and experimental evaluation of a
      novel hand-held robotic device for improving the process of peripheral
      intravenous catheterization by facilitating the needle insertion procedure. To
      our knowledge, this design is the first hand-held robotic device for assisting in
      the catheterization insertion task. Compared to the other available technologies,
      it has several unique advantages such as being compact, low-cost and able to
      reliably detect venipuncture. The system is equipped with an electrical impedance
      sensor at the tip of the catheterization needle, which provides real-time
      measurements used to supervise and control the catheter insertion process. This
      allows the robotic system to precisely position the needle within the lumen of
      the target vein, leading to enhanced catheterization success rate. Experiments
      conducted to evaluate the device demonstrated that it is also effective to
      deskill the task. Naive subjects achieved an average catheterization success rate
      of 88% on a 1.5 mm phantom vessel with the robotic device versus 12% with the
      traditional unassisted system. The results of this work prove the feasibility of
      a hand-held assistive robotic device for intravenous catheterization and show
      that such device has the potential to greatly improve the success rate of these
      difficult operations.

PMID- 29059006
TI  - Lower attendance rates in immigrant versus non-immigrant women in the Norwegian
      Breast Cancer Screening Programme.
AB  - OBJECTIVE: The Norwegian Breast Cancer Screening Programme invites women aged 50
      69 to biennial mammographic screening. Although 84% of invited women have
      attended at least once, attendance rates vary across the country. We investigated
      attendance rates among various immigrant groups compared with non-immigrants in
      the programme. METHODS: There were 4,053,691 invitations sent to 885,979 women
      between 1996 and 2015. Using individual level population-based data from the
      Cancer Registry and Statistics Norway, we examined percent attendance and
      calculated incidence rate ratios, comparing immigrants with non-immigrants, using
      Poisson regression, following women's first invitation to the programme and for
      ever having attended. RESULTS: Immigrant women had lower attendance rates than
      the rest of the population, both following the first invitation (53.1% versus
      76.1%) and for ever having attended (66.9% versus 86.4%). Differences in
      attendance rates between non-immigrant and immigrant women were less pronounced,
      but still present, when adjusted for sociodemographic factors. We also identified
      differences in attendance between immigrant groups. Attendance increased with
      duration of residency in Norway. A subgroup analysis of migrants' daughters
      showed that 70.0% attended following the first invitation, while 82.3% had ever
      attended. CONCLUSIONS: Immigrant women had lower breast cancer screening
      attendance rates. The rationale for immigrant women's non-attendance needs to be
      explored through further studies targeting women from various birth countries and
      regions.

PMID- 29059007
TI  - National study of the prevalence of gestational diabetes mellitus among Danish
      women from 2004 to 2012.
AB  - AIMS: The prevalence of gestational diabetes mellitus (GDM) is increasing
      worldwide. We studied the prevalence of GDM from 2004 to 2012 in Danish women
      aged 15-49 years using registries with records of the diagnosis of GDM at
      delivery. METHODS: We conducted a national register-based study of 12,538 women
      with a diagnosis of GDM during a pregnancy leading to a live birth in the period
      2004-2012. The diagnosis of GDM was taken from the National Patient Registry and
      combined with the total number of births at the national level from Statistics
      Denmark. Prevalence estimates were reported as crude and age-standardized using
      Danish and international data for women aged 15-49 years. RESULTS: A total of
      566,083 live births was registered in Denmark from 2004 to 2012. The age
      standardized prevalence of GDM increased from 1.7% (1095/63,465) of the total
      births in 2004 to 2.9% (1721/56,894) of the total births in 2012. During the
      period 2004-2012, the age-stratified prevalence increased from 1.1 to 1.8% among
      women aged 15-24 years, from 1.5 to 2.6% among women aged 25-34 years and from
      2.9 to 4.7% among women aged 35-49 years. The prevalence was higher among
      immigrants and their descendants than in native Danish women (4.06 and 2.09% in
      2007 vs. 4.51 and 2.72% in 2012, respectively). CONCLUSIONS: The prevalence of
      GDM in Denmark has increased across all age groups. Although the prevalence is
      low on a global scale, attention should be paid to this development by preventive
      health services.

PMID- 29059009
TI  - Inappropriate Expression of an NLP Effector in Colletotrichum orbiculare Impairs
      Infection on Cucurbitaceae Cultivars via Plant Recognition of the C-Terminal
      Region.
AB  - The hemibiotrophic pathogen Colletotrichum orbiculare preferentially expresses a
      necrosis and ethylene-inducing peptide 1 (Nep1)-like protein named NLP1 during
      the switch to necrotrophy. Here, we report that the constitutive expression of
      NLP1 in C. orbiculare blocks pathogen infection in multiple Cucurbitaceae
      cultivars via their enhanced defense responses. NLP1 has a cytotoxic activity
      that induces cell death in Nicotiana benthamiana. However, C. orbiculare
      transgenic lines constitutively expressing a mutant NLP1 lacking the cytotoxic
      activity still failed to infect cucumber, indicating no clear relationship
      between cytotoxic activity and the NLP1-dependent enhanced defense. NLP1 also
      possesses the microbe-associated molecular pattern (MAMP) sequence called nlp24,
      recognized by Arabidopsis thaliana at its central region, similar to NLPs of
      other pathogens. Surprisingly, inappropriate expression of a mutant NLP1 lacking
      the MAMP signature is also effective for blocking pathogen infection, uncoupling
      the infection block from the corresponding MAMP. Notably, the deletion analyses
      of NLP1 suggested that the C-terminal region of NLP1 is critical to enhance
      defense in cucumber. The expression of mCherry fused with the C-terminal 32 amino
      acids of NLP1 was enough to trigger the defense of cucurbits, revealing that the
      C-terminal region of the NLP1 protein is recognized by cucurbits and, then,
      terminates C. orbiculare infection.

PMID- 29059008
TI  - Narrative review of contemporary treatment options in the care of patients with
      obstructive sleep apnoea.
AB  - Snoring and obstructive sleep apnoea (OSA) are increasingly common conditions,
      and confer a significant health and socioeconomic burden. Furthermore, untreated
      OSA represents a significant mortality risk. Patients require careful assessment,
      including detailed clinical history and examination, sleep study and drug-induced
      sleep endoscopy (DISE). Although nasal continuous positive airway pressure
      (nCPAP) is the gold standard treatment for moderate and severe OSA,
      multidisciplinary team assessment is often required to develop the best treatment
      plan for an individual, especially when nasal CPAP is poorly tolerated. There is
      a wide range of medical and surgical treatment options, and following appropriate
      patient selection and assessment, a focused site-specific, often multilevel,
      intervention is indicated. There is an increasing body of evidence in the
      literature supporting these multilevel interventions and with agreement on
      standardized outcome measures more trials are likely to improve the robustness of
      these data further.

PMID- 29059011
TI  - PROGNOSTIC INDICATORS OF REHABILITATION OUTCOMES FOR ADULT AFRICAN PENGUINS (
      SPHENISCUS DEMERSUS).
AB  - :  The Southern African Foundation for the Conservation of Coastal Birds facility
      near Cape Town, South Africa, receives ~900 African Penguins ( Spheniscus
      demersus) for rehabilitation every year. Data were analyzed from 3,657 adult
      African Penguins over a 12-yr period (2002-13), and multivariate logistic
      regression analysis was used to evaluate whether individual history and clinical
      parameters upon admission could predict the outcome of rehabilitation. Penguins
      admitted due to molt or debilitation were more likely to die during
      rehabilitation than those admitted due to oiling. Individuals admitted during
      summer and spring were more likely to die during rehabilitation than those
      admitted during winter. Penguins diagnosed with Plasmodium infection at some
      point during rehabilitation were more likely to die than those that were
      consistently negative, and no significant effect was found for other blood
      parasite infections. Penguins admitted with low body mass, low total plasma
      protein, or low hematocrit were more likely to die during rehabilitation than
      those with normal values. With regard to euthanasia, penguins admitted due to
      molt, debilitation, injury, or other causes and those admitted during spring or
      with low plasma protein were more likely to be euthanized.

PMID- 29059010
TI  - Stem Cell Pathology.
AB  - Rapid advances in stem cell biology and regenerative medicine have opened new
      opportunities for better understanding disease pathogenesis and the development
      of new diagnostic, prognostic, and treatment approaches. Many stem cell niches
      are well defined anatomically, thereby allowing their routine pathological
      evaluation during disease initiation and progression. Evaluation of the
      consequences of genetic manipulations in stem cells and investigation of the
      roles of stem cells in regenerative medicine and pathogenesis of various diseases
      such as cancer require significant expertise in pathology for accurate
      interpretation of novel findings. Therefore, there is an urgent need for
      developing stem cell pathology as a discipline to facilitate stem cell research
      and regenerative medicine. This review provides examples of anatomically defined
      niches suitable for evaluation by diagnostic pathologists, describes neoplastic
      lesions associated with them, and discusses further directions of stem cell
      pathology.

PMID- 29059012
TI  - MAMMALIAN HOSTS, VECTORS, AND BACTERIAL PATHOGENS IN COMMUNITIES WITH AND WITHOUT
      BLACK-TAILED PRAIRIE DOGS ( CYNOMYS LUDOVICIANUS) IN NORTHWESTERN MEXICO.
AB  - :  The presence of keystone species can influence disease dynamics through
      changes in species diversity and composition of vector and host communities. In
      this study, we compared 1) the diversity of small mammals; 2) the prevalence,
      abundance, and intensity of arthropod vectors; and 3) the prevalence of Yersinia
      pestis, Francisella tularensis, and Bartonella spp. in vectors, between two
      grassland communities of northern Sonora, Mexico, one with (La Mesa [LM]) and one
      without (Los Fresnos [LF]) black-tailed prairie dogs ( Cynomys ludovicianus). The
      mammal community in LF exhibited higher species richness and diversity than LM,
      and species composition was different between the two communities. Flea species
      richness, prevalence, abundance, and intensity, were higher in LM than in LF. The
      most abundant fleas were Oropsylla hirsuta and Pulex simulans, and C.
      ludovicianus was the host with the highest flea intensity and richness. There was
      no serologic evidence for the presence of Y. pestis and F. tularensis in any
      community, but Bartonella spp. was present in 18% of the total samples. Some
      specificity was observed between Bartonella species, flea species, and mammal
      species. Although prairie dogs can indirectly affect the diversity and abundance
      of hosts and vectors, dynamics of vector-borne diseases at these spatial and
      temporal scales may be more dependent on the vector and pathogen specificity.

PMID- 29059013
TI  - A life in translation.

PMID- 29059014
TI  - Computational DNA binding studies of (-)-epigallocatechin-3-gallate.
AB  - The catechin family of molecules that are present in the leaves of green tea has
      been under investigation since the antioxidant and anti-inflammatory properties
      of tea were discovered. Among multiple proposed therapeutic targets of these
      molecules, the direct interaction with nucleic acids has been proposed and
      experimentally observed but without clear knowledge about the potential binding
      modes between these ligands and DNA. One of these catechin structures, (-)
      epigallocatechin gallate (EGCG), has three aromatic rings that could interact
      with double-stranded DNA via terminal base-pair stacking, intercalation, or
      through groove binding. Using enhanced sampling techniques and molecular dynamics
      simulations, we have found a stable complex between the EGCG ligand and DNA
      through intercalation of the trihydroxybenzoate aromatic ring and an ApC step.
      Moreover, we have calculated the absorption spectra of four possible binding
      modes and compared these to absorption profiles reported in the literature, and
      explored the possible DNA sequence preference for the EGCG ligand to bind. Our
      results suggest that an intercalative mode of interaction through the major
      groove is possible between the EGCG ligands and DNA with apparently very little
      DNA sequence selectivity.

PMID- 29059015
TI  - Toward Hospital Implementation of Advance Care Planning: Should Hospital
      Professionals Be Involved?
AB  - In Belgium, Advance Care Planning (ACP) is not well implemented in hospital
      practice. One of the premises for successful implementation is involving the
      adopters in the implementation process. In hospital, important adopters of ACP
      are physicians, nurses, social workers, and psychologists. First, this study
      wants to understand what the characteristics are of ACP in hospital, according to
      professionals. Second, this study aims to give an insight in the experienced
      value of ACP. Third, the experienced barriers to have ACP conversations are
      explored. Twenty-four interviews were taken and analyzed with Content Analysis
      based on Grounded Theory. Three independent external auditors surveilled the
      analysis. ACP in hospital exists by the grace of the initiative of the actors
      involved in the case. Professionals perceive fields of tension between one
      another; barriers to ACP communication. ACP is mainly considered valuable because
      it is a process that creates time for exploration and reflection.

PMID- 29059016
TI  - Determinants of working until retirement compared to a transition to early
      retirement among older workers with and without chronic diseases: Results from a
      Dutch prospective cohort study.
AB  - AIM: The ageing society and recent policy changes may lead to an increase of
      older workers with chronic diseases in the workforce. To date, it is unclear
      whether workers with chronic diseases have specific needs while employed. The aim
      of this study is to explore the differences in determinants of working until
      retirement compared to a reference group who have transitioned to early
      retirement among workers with and without chronic diseases. METHODS: Dutch
      workers aged 57-62 years ( n = 2445) were selected from an existing prospective
      cohort study, 'STREAM'. The potential determinants were categorized into:
      individual, health, work-related and social factors. Logistic regression analyses
      were performed to determine the associations between these determinants and
      working until retirement - once for workers with and once for those without
      chronic diseases. To test differences, we included an interaction term between
      the determinant and the covariate 'having a chronic disease yes/no' in the
      analyses of the total population. RESULTS: In total, 1652 (68%) persons were
      employed from 2011 to 2013. The majority of the determinants appeared to be
      similar for workers with or without a chronic disease; the interaction terms for
      these determinants and the covariate 'having a chronic disease' showed a p-value
      higher than 0.05, except for one individual factor (i.e. mastery) and one work
      related factor (i.e. autonomy), which showed a p-value below 0.05. Higher mastery
      and higher autonomy were statistically significantly associated with working
      until retirement for those with chronic diseases, whereas they were not for those
      without chronic diseases. CONCLUSIONS: Differences between workers with and
      without chronic diseases may exist for working until a statutory retirement age.
      Interventions aimed at encouraging work participation of older workers should
      make a distinction between the two groups. Autonomy at work and mastery were
      found to be factors that may promote work participation until higher age,
      specifically for older workers with chronic diseases.

PMID- 29059017
TI  - Baseline Characteristics and Technology Training of Underserved Adults With Type
      2 Diabetes in the Mobile Diabetes Detective (MoDD) Randomized Controlled Trial.
AB  - Purpose The purpose of this study is to describe the characteristics and
      technology training needs of underserved adults with type 2 diabetes mellitus
      (T2DM) who participated in a health information technology (HIT) diabetes self
      management education (DSME) intervention. Methods The baseline physiological,
      psychosocial, and technology use characteristics for 220 adults with poorly
      controlled T2DM were evaluated. Intervention participants received a 1-time
      intervention training, which included basic technology help, introduction to the
      Mobile Diabetes Detective (MoDD) website and text message features, and account
      activation that included subject-specific tailoring. Four additional on-site
      sessions for participants needing computer or Internet access or technology
      support were made available based on need. Data regarding on-site visits for
      usual care were collected. Data were analyzed using descriptive statistics and
      bivariate analysis. Results The participants were predominately Hispanic and
      female with a baseline mean A1C of 10% (86 mmol/mol). Only half of the
      participants regularly used computers or text messages in daily life. The average
      introductory MoDD training session lasted 73.6 minutes. Following training,
      approximately one-third (35%) of intervention participants returned for basic and
      MoDD-specific technology assistance at their federally qualified health center.
      The most frequently reported duration for the extra training sessions was 30 to
      45 minutes. Conclusions Training and support needs were greater than anticipated.
      Diabetes educators should assess technology abilities prior to implementing
      health information technology (HIT) diabetes self-management education (DSME) in
      underserved adults. Future research must invest resources in technology access,
      anticipate subject training, and develop new training approaches to ensure HIT
      DSME use and engagement.

PMID- 29059018
TI  - Evaluation of thromboelastography in bitches with pyometra.
AB  - We investigated the effect of pyometra on kaolin-activated thromboelastography
      (TEG). Eighteen client-owned dogs with pyometra and 8 healthy spayed dogs were
      recruited. TEG parameters and packed cell volume were determined. Results from
      spayed females and from intact females with pyometra were compared using a
      Student t-test and Wilcoxon rank sum test. Bitches with pyometra were
      hypercoagulable compared to spayed bitches as evidenced by elevated maximum
      amplitude, G, and alpha angle. There were no significant group differences in R
      time, K time, or clot lysis at 30 or 60 min. Dogs with pyometra should be
      anticipated to have hypercoagulable TEG variables, and this should be addressed
      when planning surgical and medical therapy.

PMID- 29059019
TI  - Evaluating optical hazards from plasma arc cutting.
AB  - The Health Hazard Evaluation Program of the National Institute for Occupational
      Safety and Health evaluated a steel building materials manufacturer. The employer
      requested the evaluation because of concerns about optical radiation hazards from
      a plasma arc cutting system and the need to clarify eye protection requirements
      for plasma operators, other employees, and visitors. The strength of the
      ultraviolet radiation, visible radiation (light), and infrared radiation
      generated by the plasma arc cutter was measured at various distances from the
      source and at different operating amperages. Investigators also observed
      employees performing the plasma arc cutting. Optical radiation above safe levels
      for the unprotected eyes in the ultraviolet-C, ultraviolet-B, and visible light
      ranges were found during plasma arc cutting. In contrast, infrared and
      ultraviolet-A radiation levels during plasma arc cutting were similar to
      background levels. The highest non-ionizing radiation exposures occurred when no
      welding curtains were used. A plasma arc welding curtain in place did not
      eliminate optical radiation hazards to the plasma arc operator or to nearby
      employees. In most instances, the measured intensities for visible light, UV-C,
      and UV-B resulted in welding shade lens numbers that were lower than those
      stipulated in the OSHA Filter Lenses for Protection Against Radiant Energy table
      in 29 CFR 1910.133(a)(5). [1] Investigators recommended using a welding curtain
      that enclosed the plasma arc, posting optical radiation warning signs in the
      plasma arc cutter area, installing audible or visual warning cues when the plasma
      arc cutter was operating, and using welding shades that covered the plasma arc
      cutter operator's face to protect skin from ultraviolet radiation hazards.

PMID- 29059020
TI  - Determinants of respirable quartz exposure in farming.
AB  - The objectives of this article are to quantify personal respirable quartz
      exposure on sandy, sandy loam, and clay soil farms and to identify exposure
      determinants. The methods applied included observing and examining the variables
      soil type, commodity farmed, activity, process, quartz % in respirable dust, and
      weather variables. Multiple linear regression was used to identify determinants
      of respirable quartz concentration and logistic regression was applied to
      identify determinants of respirable quartz concentration > 50 ug.m-3 (a commonly
      used reference value of over-exposure). The highest quartz concentration was 626
      ug.m-3 and 30%, 22%, and 31% of measurements were > 50 ug.m-3 for sandy, sandy
      loam, and clay soil farms, respectively. In general, the commodities livestock
      farming and cereal grains as well as the activity cereal planter operator,
      decreased humidity on the day of measurement, the mechanical processes, and
      quartz % in respirable dust (in a confounding way) were associated with higher
      respirable quartz concentrations (p <= 0.10) as well as season (p = 0.14).
      Variables associated with quartz levels above 50 ug.m-3 were cereal planter
      operator, increased quartz % in respirable dust, decreased humidity on day of
      measurement, and increased respirable dust concentration. Cereal planter operator
      (Multivariate Odds Ratio (OR) 4.56, 95% CI: 1.79-8.89) and levels of quartz % >
      10 ug.m-3 (Multivariate OR 6.01, 95% CI: 3.52-9.71 if quartz % > 10 but <= 20
      ug.m-3, and Multivariate OR 5.32, 95% CI: 2.56-8.34 if quartz % > 20 ug.m-3) were
      clear determinants of quartz over-exposure. It can therefore be concluded that
      over-exposure to quartz in farming is possible. Joint influences of more farming
      characteristics and weather variables should be included, together with soil type
      in future farming exposure assessments.

PMID- 29059021
TI  - Self-assembled supramolecular thermoreversible beta-cyclodextrin/ethylene glycol
      injectable hydrogels with difunctional Pluronic(r)127 as controlled delivery
      depot of curcumin. Development, characterization and in vitro evaluation.
AB  - This study aimed to design a novel thermoreversible compact self-assembled host
      macromolecule based on beta-cyclodextrin and low molecular weight ethylene glycol
      with a difunctional guest molecule i.e. poly (ethylene oxide)-poly (propylene
      oxide)-poly (ethylene oxide) tri-block co-polymer (Pluronic(r) 127) through host
      guest inclusion complexation in aqueous media using cold method. The injectable
      thermoreversible self-assembled supramolecular hydrogel was developed to
      encapsulate hydrophobic curcumin as anti-malignant agent and for controlled
      delivery to systemic circulation after in vivo application through subcutaneous
      route. As reversible supramolecular assembly, the thermoresponsive gels showed a
      unique structure-related reversible gel to sol transition above and below LCST
      determined via tube titling method. The rheological measurements of the
      supramolecular hydrogels showed a viscoelastic structure. Optical transmittance
      of supramolecular assembly also confirmed the thermoreversible sol-gel
      transitions. The strong potential of supramolecular assembly as injectable
      controlled delivery was assessed using curcumin as model active pharmaceutical
      ingredient for in vitro release experiments. The release experiments conducted in
      various dissolution medias and at different temperature programs showed maximum
      curcumin release in phosphate buffer solution (7.4) at 35  degrees C. methyl
      thiazolyl tetrazolium assay was used to assess the safety and efficacy of self
      assembled supramolecular injectable hydrogels. In vitro cytotoxicity study showed
      that blank supramolecular gels are non-toxic to the L929 cells. While curcumin
      released from supramolecular injectable hydrogels (Cur-beta-CD/EG-PF127) has the
      ability to show pharmacological activity and kill the cancer cells. Furthermore
      the formation of channel type inclusion complex was studied through Fourier
      transformed infra-red spectroscopy, X-ray diffraction, thermogravimetric
      analysis, differential scanning calorimetric and scanning electron microscopic
      analysis.

PMID- 29059022
TI  - Anatomical abnormalities of the pelvic venous system and their implications for
      endovascular management of pelvic venous reflux.
AB  - Background Pelvic venous reflux is often treated with pelvic vein embolisation;
      however, atypical pelvic venous anatomy may provide therapeutic challenges.
      Methods We retrospectively reviewed seven patient files and reported symptoms,
      diagnostic imaging, aberrant anatomy and means by which the interventional
      radiologist successfully completed the procedure. Any follow-up data were
      included if available. Results Four anatomical abnormalities were found: internal
      iliac veins draining into the contralateral common iliac vein, duplicated
      inferior vena cava, reverse-angle renal veins with atypical left ovarian vein
      drainage and direct drainage of the internal iliac vein to the inferior vena
      cava. All patients were successfully treated with pelvic vein embolisation.
      Conclusion Abnormal embryologic development may cause variable pelvic venous
      anatomy. Knowledge of this will enable interventional radiologists to
      successfully treat such patients.

PMID- 29059023
TI  - New data for venous thromboembolism in patients with small cell lung cancer: A
      review.
AB  - Malignancy is an important predisposing factor for thromboembolic disease.
      Patients with malignancy display 4 to 10 times greater risk than the general
      population. As for lung cancer, that risk seems to further increase and become up
      to 20 times higher. The aim of this article is to review the International
      literature in order to highlight for the first time, the correlation between
      thromboembolic disease and small cell lung cancer. PubMed, Medline and Embase
      databases were searched from 1990 up to 2016, for retrospective and prospective
      studies that investigate the correlation between thromboembolic disease and small
      cell lung cancer. The incidence rate of thromboembolic disease found in these
      studies ranged between 6.8% and 11.5%. Thromboembolic disease is associated with
      a reduced survival in patients with small cell lung cancer and six factors seemed
      to increase the risk of thromboembolism: chemotherapy, cisplatin treatment,
      smoking, extensive disease, the infiltration of the superior vena cava and
      multiple concomitant diseases. Thromboembolic disease shows an increased
      incidence in patients with small cell lung cancer and more research with well
      designed studies is required in order to study in detail the anticoagulation
      treatment and the survival in small cell lung cancer patients.

PMID- 29059024
TI  - Effect of aminaphtone on in vitro vascular permeability and capillary-like
      maintenance.
AB  - Objectives Aminaphtone, a naphtohydrochinone used in the treatment of capillary
      disorders, may affect oedema in chronic venous insufficiency. Aim of study is to
      investigate the effect of aminaphtone on vascular endothelial permeability in
      vitro and its effects on three-dimensional capillary-like structures formed by
      human umbilical vein endothelial cells. Method Human umbilical vein endothelial
      cells were treated with 50 ng/ml VEGF for 2 h and aminaphtone for 6 h.
      Permeability assay, VE-cadherin expression and Matrigel assay were performed.
      Results VEGF-induced permeability was significantly decreased by aminaphtone in a
      range concentration of 1-20 ug/ml. Aminaphtone restored VE-cadherin expression.
      Finally, 6 h pre-treatment with aminaphtone significantly preserved capillary
      like structures formed by human umbilical vein endothelial cells on Matrigel up
      to 48 h compared to untreated cells. Conclusions Aminaphtone significantly
      protects endothelium permeability and stabilises endothelial cells organised in
      capillary-like structures, modulating VE-cadherin expression. These data might
      explain the clinical benefit of aminaphtone on chronic venous insufficiency.

PMID- 29059025
TI  - Change in perception of sclerotherapy results after exposure to pre-post
      intervention photographs.
AB  - Objective: To evaluate patients' self-perception of cosmetic improvement before
      and after they were presented with pre- and postprocedure photographs after
      sclerotherapy with 75% dextrose. Methods: Treatments included sclerotherapy of
      reticular and varicose veins using 75% dextrose. All treated limbs were
      photographed and classified according to Clinical, Etiology, Anatomy, and
      Pathology classification and Venous Clinical Severity Score pre- and
      posttreatment. The patients were queried before and after viewing the photos
      during these visits and indicated if they were very unsatisfied, dissatisfied,
      satisfied, or very satisfied. Nonparametric kappa correlation coefficient and a
      Chi square test were used to measure associations among agreement (p < 0.05
      indicated statistical significance). The paired Wilcoxon test was used to compare
      statistical differences in mean Venous Clinical Severity Scores measured at
      different times (p < 0.05 indicated statistical significance). Data were analyzed
      using STATA software (version 12). Results: Individuals were more satisfied with
      the results of sclerotherapy after exposure to images portraying their limbs two
      months after the procedure (p < 0.0028) [corrected]. This effect was maintained
      six months after sclerotherapy (p = 0.0027). Conclusion: Patient exposure to pre-
      and postsurgical photographs is a simple intervention with the potential of
      improving patient satisfaction up to six months after treatment with
      sclerotherapy

PMID- 29059026
TI  - Impact of fluoroquinolone prophylaxis on infectious-related outcomes after
      hematopoietic cell transplantation.
AB  - Background Patients immediately post-hematopoietic cell transplantation are at
      high risk for bacteremia. Judicious prophylactic antimicrobial utilization must
      balance anticipated benefits (reduction infections) versus risk (bacterial
      resistance, Clostridium difficile) . Objective To compare infectious outcomes
      (primary: incidence bacteremia; secondary: febrile neutropenia, C. difficile,
      susceptibility of bacteremia, time to discharge and 30-day mortality) between
      hematopoietic cell transplantation who received fluoroquinolone prophylaxis to
      those who did not. Methods A local institutional review board-approved
      retrospective study was conducted on all hematopoietic cell transplantation
      patients ( n = 171) comparing those who received fluoroquinolone prophylaxis ( n
      = 105) to those who did not ( n = 66). Data included infectious outcomes and
      mortality for the first 30 days post-hematopoietic cell transplantation. Chi
      squared was performed for categorical variables (GraphPad Software Inc., 2015).
      Secondary analysis compared outcomes within autologous and allogeneic sub-groups.
      Results Bacteremia was significantly lower for the overall cohort receiving
      fluoroquinolone (median duration eight days) versus those without fluoroquinolone
      (15.2% vs. 31.8%; P < 0.01). No difference was seen in C. difficile infection ( P
      = 0.81) or 30-day mortality (2.9% vs. 4.5%; P = 0.67). In the autologous sub
      group ( n = 115), bacteremia was significantly lower in the fluoroquinolone
      cohort (8.5% vs. 27.3%; P = 0.0069), while no differences were seen in C.
      difficile infection ( P = 1) or 30-day mortality ( P = 1). In the allogeneic sub
      group ( n = 56), there was no difference between those with and without
      fluoroquinolone in bacteremia (29.4% vs. 40.9%; P = 0.4) or C. difficile ( P =
      0.72); however, there was a trend toward improved 30-day mortality (2.9% vs.
      9.1%; P = 0.55). Conclusions Fluoroquinolone prophylaxis reduces incidence of
      bacteremia in autologous hematopoietic cell transplantation without increasing C.
      difficile after hematopoietic cell transplantation.

PMID- 29059027
TI  - Physicochemical stability of carfilzomib (Kyprolis(r)) containing solutions in
      glass vials, ready-to-administer plastic syringes and infusion bags over a 28-day
      storage period.
AB  - Centralized aseptic preparation of ready-to-administer carfilzomib containing
      parenteral solutions in plastic syringes and polyolefine (PO) infusion bags needs
      profound knowledge about the physicochemical stability in order to determine the
      beyond-use-date of the preparations. Therefore, the purpose of this study was to
      determine the physicochemical stability of carfilzomib solution marketed as
      Kyprolis(r) powder for solution for infusion. Reconstituted solutions and ready
      to-administer preparations of Kyprolis(r) stored under refrigeration (2-8C) or at
      room temperature (25C) were analyzed at predetermined intervals over a maximum
      storage period of 28 days. Chemical stability of carfilzomib was planned to be
      determined with a stability-indicating reversed-phase high-performance liquid
      chromatography assay. Physicochemical stability was planned to be determined by
      visual inspection of clarity and color as well as pH measurement. The study
      results show that reconstituted carfilzomib containing parenteral solutions are
      stable in glass vials as well as diluted solutions in plastic syringes and PO
      infusion bags over a period of at least 28 days when stored light protected under
      refrigeration. When stored at room temperature, reconstituted and diluted
      carfilzomib solutions are physicochemically stable over 14 days and 10 days,
      respectively. The physicochemical stability of carfilzomib infusion solutions
      allows cost-saving pharmacy-based centralized preparation of ready-to-administer
      preparations.

PMID- 29059028
TI  - Introduction of a dose-banding system for parenteral chemotherapy on a
      haematology-oncology day ward.
AB  - Introduction The increasing incidence of cancer and the finite capacity of
      hospital aseptic compounding units pose a serious challenge to the provision of
      cancer care. Chemotherapy dose-banding is a method of rationalising parenteral
      chemotherapy dosing and supply, whereby patient-individualised doses are rounded
      to predetermined banded doses. The banded doses may be outsourced as stock items
      which increases the supply capacity of the aseptic compounding unit. Methods
      Kotter's 8-step change management model was used to structure the implementation
      of dose-banding of 5-fluorouracil 46-h infusers on the haematology-oncology day
      ward in St. James's Hospital, Dublin. The impact of dose-banding on local
      practice was assessed through pre- and post-implementation surveys of
      stakeholders. Results In-house surveys of pharmacy, medical and nursing staff
      identified a generally favourable attitude towards implementing changes in the
      parenteral chemotherapy supply system, with some resistance to change evident.
      Dose-banding of 5-fluorouracil 46-h infusers was implemented successfully on the
      haematology-oncology day ward. Dose rationalisation and flexibility of re
      allocation of standard banded doses between patients were the primary benefits of
      dose-banding found. Post-implementation surveys showed that clinical staff were
      in favour of adopting dose-banding into standard practice; however, they were
      cautious about the degree to which the results of this limited study would be
      translated into substantive benefits if dose-banding was adopted for all suitable
      preparations. Conclusion The success of the implementation process and the
      favourable opinions of stakeholders shown in the post-implementation survey
      enabled the dose-banding service to be extended to a further nine drugs. Kotter's
      8-step change management model was a useful tool for structuring this process
      change in St. James's Hospital.

PMID- 29059029
TI  - Uptake of HIV testing during antenatal care in Honduras.
AB  - In order to interrupt vertical transmission of HIV, the WHO recommends universal
      HIV testing during antenatal care (ANC), a policy that has been adopted by the
      Ministry of Health in Honduras. We examined HIV counseling and testing practices
      during ANC in the Honduras Demographic and Health Survey to understand compliance
      with this established standard of care. Among currently married women with a
      child aged five years or younger who attended ANC, only 66% recalled being
      offered HIV testing during ANC, yet 95% of those got tested. Older, less literate
      women who lived in a rural area, a small household, or had an older husband were
      significantly less likely to recall being offered HIV testing. These findings
      highlight necessary revisions to ANC protocols to ensure that all women in
      Honduras get HIV testing to interrupt mother-to-child transmission.

PMID- 29059030
TI  - Sexually active students' acceptability of providing saline oral samples for
      future human papillomavirus testing.

PMID- 29059031
TI  - Dolutegravir-induced liver injury leading to sub-acute liver failure requiring
      transplantation: a case report and review of literature.
AB  - A patient with human immunodeficiency virus-1 infection presented with sub-acute
      liver failure, temporally related to commencement of an antiretroviral therapy
      regimen containing dolutegravir (Triumeq). The patient was not a carrier of HLA
      B5701, and abacavir hypersensitivity was unlikely. We believe this is the first
      report of severe dolutegravir-related hepatotoxicity resulting in sub-acute liver
      failure and transplantation and highlights a potential need for closer monitoring
      after drug initiation.

PMID- 29059032
TI  - Rapid testing and treatment for sexually transmitted infections improve patient
      care and yield public health benefits.
AB  - : A service evaluation of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae
      (NG) testing and result notification in patients attending a rapid testing
      service (Dean Street Express [DSE]) compared with those attending an existing
      'standard' sexual health clinic (56 Dean Street [56DS]), and modelling the impact
      of the new service from 1 June 2014 to 31 May 2015. PRIMARY OUTCOME: time from
      patients' sample collection to notification of test results at DSE compared with
      56DS. Secondary outcomes estimated using a model: number of transmissions
      prevented and the number of new partner visits avoided and associated cost
      savings achieved due to rapid testing at DSE. In 2014/15, there were a total of
      81,352 visits for CT/NG testing across 56DS (21,086) and DSE (60,266). Rapid
      testing resulted in a reduced mean time to notification of 8.68 days: 8.95 days
      for 56DS (95% CI 8.91-8.99) compared to 0.27 days for DSE (95% CI 0.26-0.28). Our
      model estimates that rapid testing at DSE would lead to 196 CT and/or NG
      transmissions prevented (2.5-97.5% centile range = 6-956) and lead to annual
      savings attributable to reduced numbers of partner attendances of L124,283 (2.5
      97.5% centile range = L4260-590,331). DSE, a rapid testing service for
      asymptomatic infections, delivers faster time to result notification for CT
      and/or NG which enables faster treatment, reduces infectious periods and leads to
      fewer transmissions, partner attendances and clinic costs.

PMID- 29059033
TI  - Patients' perspectives on the development of HIV services to accommodate ageing
      with HIV: a qualitative study.
AB  - The objective of this study was to identify the aspects of healthcare that are
      most valued by people with HIV and to describe their concerns and preferences for
      the future delivery of services for non-HIV-related illness. Twelve focus groups
      of people receiving HIV care were conducted in community settings in South-East
      England. Groups were quota sampled based on age, gender, sexual orientation and
      ethnicity. Data were analysed using Framework Analysis. The results showed that
      among the 74 respondents (61% male), a preference for maintaining all care within
      specialist HIV clinics was commonplace, but was highest among participants with
      more extensive histories of HIV and comorbidities. Participants valued care
      coordination, inter-service communication and timely updates to medical notes.
      There were high levels of concern around HIV skills in general practices and the
      capacity of general practitioners to manage patient confidentiality or deal
      appropriately with the emotional and social challenges of living with HIV.
      Participants valued, and had an overall preference for, the specialist knowledge
      and skills of HIV services, suggesting that non-HIV-specialist services will need
      to build their appeal if they are to have a greater future role in the care of
      people with HIV. Particular concerns that should be addressed include: patient
      confidence in the HIV knowledge and skills of non-specialist service providers;
      clear processes for prescribing and referrals; improved levels of care
      coordination and communication between services and increased patient confidence
      in the capacity of primary care to maintain confidentiality and to appreciate the
      stigma associated with HIV.

PMID- 29059034
TI  - The use of technology to find sexual health information online among men who have
      sex with men in Hanoi, Vietnam, 2016.
AB  - In an era where mobile phones and computers are ubiquitous, technology-based
      interventions to reduce HIV and other sexually transmitted infections (STIs) have
      great potential to reach high-risk groups, including men who have sex with men
      (MSM). This study aimed to examine technology usage to find sexual health
      information online among MSM in Hanoi, Vietnam. A cross-sectional study of 205
      MSM in Hanoi was conducted from February to May 2016. Overall, 50.7% of
      participants reported having used a smartphone, computer, or tablet to find
      HIV/STI testing locations in the past year, and 75.1% reported having used such
      devices to find other HIV/STI information online. Unemployment (adjusted
      prevalence ratio [aPR]: 1.13, 95%CI: 1.00-1.28) and having been tested for HIV
      (aPR: 1.27, 95%CI: 1.07-1.51) were significantly associated with using technology
      to find online sexual health information. MSM who had ever exchanged sex for
      money or drugs (aPR: 0.80; 95%CI: 0.68-0.94) were less likely to use technology
      to find sexual health information online. Technology is a promising platform for
      HIV/STI prevention programs among MSM, with the potential to reach different
      subgroups. Further efforts to develop technology-based interventions tailored to
      the needs of the MSM communities in Hanoi and to encourage MSM who were not
      currently seeking sexual health information and testing services online to do so
      are necessary.

PMID- 29059035
TI  - Nocardia beijingensis pericarditis presenting with cardiac tamponade: A case
      report.
AB  - We report the first case of Nocardia beijingensis pericarditis in a 32-year-old
      HIV-infected patient. He presented with cardiac tamponade after failing to
      respond to treatment for smear-negative pulmonary and pericardial tuberculosis
      (TB). The pericardial fluid was examined several times before it eventually
      revealed filamentous branching organisms in Gram and modified acid-fast bacilli
      stain. The culture grew Nocardia spp. and was identified by 16s rRNA sequencing
      as N. beijingensis. Eight previously reported cases of Nocardia pericarditis in
      HIV-infected patients were caused by Nocardia asteroides. All patients had low
      CD4 cell count (range: 17-239 cells/mm3) and 50% of patients were treated for
      tuberculous pericarditis prior to making the correct diagnosis of Nocardia
      pericarditis. This report revisits the issue of nocardiosis as a great TB
      mimicker. It should always be considered in the differential diagnosis among HIV
      infected patients suspected of having pericardial TB that is failing treatment.

PMID- 29059036
TI  - Deep Learning with Convolutional Neural Network for Differentiation of Liver
      Masses at Dynamic Contrast-enhanced CT: A Preliminary Study.
AB  - Purpose To investigate diagnostic performance by using a deep learning method
      with a convolutional neural network (CNN) for the differentiation of liver masses
      at dynamic contrast agent-enhanced computed tomography (CT). Materials and
      Methods This clinical retrospective study used CT image sets of liver masses over
      three phases (noncontrast-agent enhanced, arterial, and delayed). Masses were
      diagnosed according to five categories (category A, classic hepatocellular
      carcinomas [HCCs]; category B, malignant liver tumors other than classic and
      early HCCs; category C, indeterminate masses or mass-like lesions [including
      early HCCs and dysplastic nodules] and rare benign liver masses other than
      hemangiomas and cysts; category D, hemangiomas; and category E, cysts).
      Supervised training was performed by using 55 536 image sets obtained in 2013
      (from 460 patients, 1068 sets were obtained and they were augmented by a factor
      of 52 [rotated, parallel-shifted, strongly enlarged, and noise-added images were
      generated from the original images]). The CNN was composed of six convolutional,
      three maximum pooling, and three fully connected layers. The CNN was tested with
      100 liver mass image sets obtained in 2016 (74 men and 26 women; mean age, 66.4
      years +/- 10.6 [standard deviation]; mean mass size, 26.9 mm +/- 25.9; 21, nine,
      35, 20, and 15 liver masses for categories A, B, C, D, and E, respectively).
      Training and testing were performed five times. Accuracy for categorizing liver
      masses with CNN model and the area under receiver operating characteristic curve
      for differentiating categories A-B versus categories C-E were calculated. Results
      Median accuracy of differential diagnosis of liver masses for test data were
      0.84. Median area under the receiver operating characteristic curve for
      differentiating categories A-B from C-E was 0.92. Conclusion Deep learning with
      CNN showed high diagnostic performance in differentiation of liver masses at
      dynamic CT. (c) RSNA, 2017 Online supplemental material is available for this
      article.

PMID- 29059037
TI  - Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input
      Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum
      based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups.
AB  - Purpose To determine whether dual-input perfusion computed tomography (CT) can
      predict therapeutic response and prognosis in patients who underwent chemotherapy
      for non-small cell lung cancer (NSCLC). Materials and Methods The institutional
      review board approved this study and informed consent was obtained. Sixty-six
      patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who
      underwent chemotherapy were enrolled. Patients were separated into three groups:
      those who received chemotherapy with bevacizumab (BV) (n = 20), those who
      received two-agent platinum-based therapy without BV (n = 25), and those who
      received other non-BV treatment (n = 21). Before treatment, pulmonary artery
      perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were
      calculated. Predictors of tumor reduction after two courses of chemotherapy and
      prognosis were identified by using univariate and multivariate analyses.
      Covariates included were age, sex, patient's performance status, baseline maximum
      diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP.
      For multivariate analyses, multiple linear regression analysis for tumor
      reduction rate and Cox proportional hazards model for prognosis were performed,
      respectively. Results Pretreatment BAP was independently correlated with tumor
      reduction rate after two courses of chemotherapy in the BV treatment group (P =
      .006). Pretreatment BAP was significantly associated with a highly cumulative
      risk of death (P = .006) and disease progression after chemotherapy (P = .015) in
      the BV treatment group. Pretreatment PAP and clinical parameters were not
      significant predictors of therapeutic effect or prognosis in three treatment
      groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to
      be a promising tool to help predict responses to chemotherapy with BV in patients
      with NSCLC. (c) RSNA, 2017.

PMID- 29059038
TI  - Comprehensive Assessment of Coronary Artery Disease by Using First-Pass Analysis
      Dynamic CT Perfusion: Validation in a Swine Model.
AB  - Purpose To retrospectively validate a first-pass analysis (FPA) technique that
      combines computed tomographic (CT) angiography and dynamic CT perfusion
      measurement into one low-dose examination. Materials and Methods The study was
      approved by the animal care committee. The FPA technique was retrospectively
      validated in six swine (mean weight, 37.3 kg +/- 7.5 [standard deviation])
      between April 2015 and October 2016. Four to five intermediate-severity stenoses
      were generated in the left anterior descending artery (LAD), and 20 contrast
      material-enhanced volume scans were acquired per stenosis. All volume scans were
      used for maximum slope model (MSM) perfusion measurement, but only two volume
      scans were used for FPA perfusion measurement. Perfusion measurements in the LAD,
      left circumflex artery (LCx), right coronary artery, and all three coronary
      arteries combined were compared with microsphere perfusion measurements by using
      regression, root-mean-square error, root-mean-square deviation, Lin concordance
      correlation, and diagnostic outcomes analysis. The CT dose index and size
      specific dose estimate per two-volume FPA perfusion measurement were also
      determined. Results FPA and MSM perfusion measurements (PFPA and PMSM) in all
      three coronary arteries combined were related to reference standard microsphere
      perfusion measurements (PMICRO), as follows: PFPA_COMBINED = 1.02 PMICRO_COMBINED
      + 0.11 (r = 0.96) and PMSM_COMBINED = 0.28 PMICRO_COMBINED + 0.23 (r = 0.89). The
      CT dose index and size-specific dose estimate per two-volume FPA perfusion
      measurement were 10.8 and 17.8 mGy, respectively. Conclusion The FPA technique
      was retrospectively validated in a swine model and has the potential to be used
      for accurate, low-dose vessel-specific morphologic and physiologic assessment of
      coronary artery disease. (c) RSNA, 2017.

PMID- 29059039
TI  - Ambulance disinfection using Ultraviolet Germicidal Irradiation (UVGI): Effects
      of fixture location and surface reflectivity.
AB  - Ambulances are frequently contaminated with infectious microorganisms shed by
      patients during transport that can be transferred to subsequent patients and
      emergency medical service workers. Manual decontamination is tedious and time
      consuming, and persistent contamination is common even after cleaning.
      Ultraviolet germicidal irradiation (UVGI) has been proposed as a terminal
      disinfection method for ambulance patient compartments. However, no published
      studies have tested the use of UVGI in ambulances. The objectives of this study
      were to investigate the efficacy of a UVGI system in an ambulance patient
      compartment and to examine the impact of UVGI fixture position and the UV
      reflectivity of interior surfaces on the time required for disinfection. A UVGI
      fixture was placed in the front, middle, or back of an ambulance patient
      compartment, and the UV irradiance was measured at 49 locations. Aluminum sheets
      and UV-reflective paint were added to examine the effects of increasing surface
      reflectivity on disinfection time. Disinfection tests were conducted using
      Bacillus subtilis spores as a surrogate for pathogens. Our results showed that
      the UV irradiance varied considerably depending upon the surface location. For
      example, with the UVGI fixture in the back position and without the addition of
      UV-reflective surfaces, the most irradiated location received a dose of UVGI
      sufficient for disinfection in 16 s, but the least irradiated location required
      15 hr. Because the overall time required to disinfect all of the interior
      surfaces is determined by the time required to disinfect the surfaces receiving
      the lowest irradiation levels, the patient compartment disinfection times for
      different UVGI configurations ranged from 16.5 hr to 59 min depending upon the
      UVGI fixture position and the interior surface reflectivity. These results
      indicate that UVGI systems can reduce microbial surface contamination in
      ambulance compartments, but the systems must be rigorously validated before
      deployment. Optimizing the UVGI fixture position and increasing the UV
      reflectivity of the interior surfaces can substantially improve the performance
      of a UVGI system and reduce the time required for disinfection.

PMID- 29059040
TI  - Pilot Test of a Culturally Appropriate Diabetes Prevention Intervention for At
      Risk Latina Women.
AB  - Purpose The purpose of the study was to test the preliminary effectiveness,
      feasibility, and acceptability of a peer-led, culturally appropriate, Diabetes
      Prevention Program (DPP)-based lifestyle intervention for Latina women at high
      risk for type 2 diabetes (T2DM). Methods Participants (N = 61) were
      overweight/obese (body mass index [BMI] >=25) Latina women with no diabetes, at
      elevated risk either due to midlife age (45-65 years; n = 37) or history of
      gestational diabetes mellitus (n = 24). The study used a 1-group pretest-posttest
      design and offered 12 weeks of peer-led education sessions in a community
      setting. The intervention targeted physical activity and dietary behaviors to
      facilitate weight reduction and included culturally appropriate content, age
      specific health information, and stress/emotion management strategies. Clinical
      and self-report assessments were conducted at baseline, month 3, and month 6.
      Results Mean participant age was 47.8 years (SD = 10.8). Most (91.2%) were born
      in Mexico, and 43.3% had a ninth-grade education or less. At month 6,
      participants achieved a mean reduction of 4.1% body weight (7 lb [3.2 kg]).
      Statistically significant improvements were observed for dietary behaviors,
      stress, and depression symptoms. Attrition was low, 5% (3 women). Focus groups
      indicated that intervention content increased knowledge, was applicable, highly
      valued, culturally relevant, and would be recommended to others. Conclusions This
      culturally tailored DPP adaptation was feasible and acceptable for 2 groups of
      Latina women at high-risk for T2DM and showed preliminary effectiveness in
      reducing weight and modifying self-reported dietary behaviors, stress, and
      depression symptoms. Further research is needed to identify ways to enhance
      weight loss and diabetes prevention in this at-risk, underserved population.

PMID- 29059041
TI  - Seroprevalence of hepatitis E virus among blood donors in northern Italy
      (Sondrio, Lombardy) determined by three different assays.

PMID- 29059042
TI  - K-antigen blocking in a case of haemolytic disease of the foetus and newborn.

PMID- 29059043
TI  - The Urology Residency Program in Israel-Results of a Residents Survey and
      Insights for the Future.
AB  - OBJECTIVE: Urology practice has undergone several changes in recent years mainly
      related to novel technologies introduced. We aimed to get the residents'
      perspective on the current residency program in Israel and propose changes in it.
      METHODS: A web-based survey was distributed among urology residents. RESULTS: 61
      residents completed the survey out of 95 to whom it was sent (64% compliance). A
      total of 30% replied that the 9 months of mandatory general surgery rotation
      contributed to their training, 48% replied it should be shortened/canceled, and
      43% replied that the Step A exam (a mandatory written certifying exam) in general
      surgery was relevant to their training. A total of 37% thought that surgical
      exposure during the residency was adequate, and 28% considered their training
      "hands-on." Most non-junior residents (post-graduate year 3 and beyond) reported
      being able to perform simple procedures such as circumcision and transurethral
      resections but not complex procedures such as radical and laparoscopic
      procedures. A total of 41% of non-junior residents practice at a urology clinic.
      A total of 62% of residents from centers with no robotics replied its absence
      harmed their training, and 85% replied they would benefit from a robotics
      rotation. A total of 61% of residents from centers with robotics replied its
      presence harmed their training, and 72% replied they would benefit from an open
      surgery rotation. A total of 82% of the residents participated in post-graduate
      courses, and 81% replied they would engage in a clinical fellowship. CONCLUSION:
      Given the survey results we propose some changes to be considered in the
      residency program. These include changes in the general surgery rotation and
      exam, better surgical training, possible exchange rotations to expose residents
      to robotic and open surgery (depending on the availability of robotics in their
      center), greater out-patient urology clinic exposure, and possible changes in the
      basic science period.

PMID- 29059044
TI  - Expanding the Utilization of Robotic Procedures in Urologic Surgery.
AB  - Although the word "robot" was coined in 1921, only close to 70 years later were
      robotic devices developed to assist during surgery. Urology has always been at
      the forefront of endoscopic, minimally invasive, and robotic developments in
      medicine. Robotic prostatectomy signaled the emerging role of robotic surgery in
      urology, but since then it has been applied to every urologic laparoscopic
      procedure.

PMID- 29059045
TI  - Update on Screening for Urological Malignancies.
AB  - Urological malignancies are a major source of morbidity and mortality in men over
      40. Screening for those malignancies has a potential benefit of reducing both.
      However, even after more than two decades of screening for prostate cancer, the
      implications of most resulting information are still a matter of debate.
      Controversy extends over several aspects of prostate cancer screening programs,
      including age of onset, defining populations at risk, most appropriate intervals,
      as well as the optimal methods to be used for screening. The medical community is
      still divided regarding the effectiveness of prostate cancer-related death
      prevention and its benefits-to-harms ratio, reflecting an inconsistency regarding
      screening recommendations. Similarly, benefits of screening for urothelial and
      kidney tumors are yet lacking high-level evidence, although recent evidence
      supports screening of populations at risk. Clearly, the current era of evolving
      molecular and genetic biomarkers harbors the potential to change screening
      practice. In this paper, we review current guidelines as well as giving an update
      on new developments which might influence screening strategies in common
      urological malignancies.

PMID- 29059046
TI  - Artificial Sperm: New Horizons in Procreation.
AB  - Azoospermia, the absence of any sperm cells from the ejaculated semen, poses a
      real challenge to the fertility urologist. While there are options to create
      happy families for azoospermic couples, such as the use of donor sperm and
      adoption, most couples still want to have genetically related offspring. Advances
      in urology, gynecology, and fertility laboratory technologies allow surgical
      sperm retrieval in azoospermic men and achievement of live births for many, but
      not all azoospermic couples. At present, there are extensive research efforts in
      several directions to create new fertility options by creating "artificial sperm
      cells." While these new horizons are exciting, there are significant obstacles
      that must be overcome before such innovative solutions can be offered to
      azoospermic couples. The present review article defines the problem, describes
      the theoretical basis for creation of artificial genetically related sperm cells,
      and provides an update on current successes and challenges in the long tortuous
      path to achieve the ultimate goal: enabling every azoospermic couple to have
      their own genetically related offspring. Hopefully, these research efforts will
      ripen in the foreseeable future, resulting in the ability to create artificial
      sperm cells and provide such couples with off-the-shelf solutions and fulfilling
      their desire to parent genetically related healthy babies.

PMID- 29059047
TI  - Peas in a Pod? The Similarities between UFPs and Nanoparticles Yield Research
      Opportunities.

PMID- 29059048
TI  - Short-wavelength free-electron laser sources and science: a review.
AB  - This review is focused on free-electron lasers (FELs) in the hard to soft x-ray
      regime. The aim is to provide newcomers to the area with insights into: the basic
      physics of FELs, the qualities of the radiation they produce, the challenges of
      transmitting that radiation to end users and the diversity of current scientific
      applications. Initial consideration is given to FEL theory in order to provide
      the foundation for discussion of FEL output properties and the technical
      challenges of short-wavelength FELs. This is followed by an overview of existing
      x-ray FEL facilities, future facilities and FEL frontiers. To provide a context
      for information in the above sections, a detailed comparison of the photon pulse
      characteristics of FEL sources with those of other sources of high brightness x
      rays is made. A brief summary of FEL beamline design and photon diagnostics then
      precedes an overview of FEL scientific applications. Recent highlights are
      covered in sections on structural biology, atomic and molecular physics,
      photochemistry, non-linear spectroscopy, shock physics, solid density plasmas. A
      short industrial perspective is also included to emphasise potential in this
      area.

PMID- 29059049
TI  - Catalytic chemical vapor deposition of large-area uniform two-dimensional
      molybdenum disulfide using sodium chloride.
AB  - The effective synthesis of atomically thin molybdenum disulfides (MoS2) of high
      quality and uniformity over a large area is essential for their use in electronic
      and optical devices. In this work, we synthesize MoS2 that exhibit a high quality
      and large area uniformity using chemical vapor deposition (CVD) with volatile S
      organic compound and NaCl catalysts. In the latter process, the NaCl enhances the
      growth rate (5 min for synthesis of monolayer MoS2) and purity of the synthesized
      MoS2. The optical microscopy, Raman spectroscopy, x-ray photoemission
      spectroscopy, photoluminescence, and transmission electron microscopy
      measurements indicate that the NaCl-CVD MoS2 has a large grain size, clear Raman
      shift, strong photoluminescence, good stoichiometry, and 6-fold coordination
      symmetry. Moreover, we demonstrate that the electron mobility (10.4 cm2 V-1 s-1)
      and on/off current ratio (3 * 107) of monolayer MoS2 measured using a field
      effect transistor are comparable to those of previously reported MoS2 synthesized
      using CVD.

PMID- 29059050
TI  - Improvement of SET variability in TaO x based resistive RAM devices.
AB  - Improvement or at least control of variability is one of the key challenges for
      Redox based resistive switching memory technology. In this paper, we investigate
      the impact of a serial resistor as a voltage divider on the SET variability in
      Pt/Ta2O5/Ta/Pt nano crossbar devices. A partial RESET in a competing
      complementary switching (CS) mode is identified as a possible failure mechanism
      of bipolar switching SET in our devices. Due to a voltage divider effect, serial
      resistance value shows unequal impact on switching voltages of both modes which
      allows for a selective suppression of the CS mode. The impact of voltage divider
      on SET variability is demonstrated. A combination of appropriate write voltage
      and serial resistance allows for a significant improvement of the SET
      variability.

PMID- 29059051
TI  - Extension of the Fermi-Eyges most-likely path in heterogeneous medium with prior
      knowledge information.
AB  - Particle imaging suffers from poor spatial resolution due to the multiple Coulomb
      scattering deflections undergone by the particles throughout their path. To
      account for these deflections, a most-likely path (MLP) formalism was developed
      based on a Bayesian adaption of the Fermi-Eyges theory. Previous work calculated
      the MLP formalism in a homogeneous water medium as an initial estimate. However,
      this potentially reduces the accuracy of the MLP estimate as well as the
      achievable resolution of the subsequent tomographic reconstruction. This work
      investigates the potential gain of introducing prior-knowledge on the medium
      composition and density to improve the MLP accuracy. To do so, a Monte Carlo (MC)
      Geant4 algorithm was used to simulate protons ([Formula: see text]) crossing
      three different anthropomorphic phantoms representing the lung, abdomen, and
      head. The prior-knowledge information is gathered from (1) the MC simulation for
      ground-truth (MLP-GT), or from (2) a recent DECT material decomposition technique
      (MLP-DECT). The reconstructed path accuracy using prior-knowledge methods is
      compared with (3) the path reconstructed in homogeneous water (MLP-Water) and (4)
      a path reconstruction method where the proton path is projected onto a Hull at
      the boundary of the phantom with a subsequent MLP-Water calculation (MLP-Hull).
      For each path reconstruction method, the maximal root-mean-square error (RMSmax)
      is compared between the reconstructed and the MC path. In every phantom, the
      RMSmax is decreased between the MLP-Water and the three other path algorithms
      that take into account heterogeneities ([Formula: see text] for the lung,
      [Formula: see text] for the abdomen and [Formula: see text] for the head), with
      no significant differences between each (MLP-DECT, MLP-GT and MLP-Hull). In
      conclusion, the introduction of prior-knowledge in the MLP formalism decreases
      the RMS uncertainty to the MC path, but no further than the use of a simpler Hull
      contour algorithm. The use of this Hull algorithm is suggested for future
      particle imaging applications.

PMID- 29059052
TI  - Synthesis of 3D-MoO2 microsphere supported MoSe2 as an efficient electrocatalyst
      for hydrogen evolution reaction.
AB  - Many efforts have been devoted to the exploration of non-noble-metal
      electrocatalysts for the hydrogen evolution reaction (HER) in recent years. Here,
      we have developed a 3D-MoO2 microsphere supported MoSe2 for HER, via a facile
      hydrothermal approach followed by selenylation treatment. Loosely stacked MoSe2
      layers are formed on the conductive MoO2 surface, and act as active sites for
      HER. Meanwhile, the metallic inner MoO2 facilitates electron transport for proton
      reduction. In addition, the MoSe2 could protect the inner MoO2 from the acidic
      electrolyte in the HER precess. Significantly, the as-synthesized MoO2/MoSe2
      exhibits excellent catalytic activity for HER, characterised by a low onset
      potential of -101 mV vs reversible hydrogen electrode, a small overpotential of
      167 mV at a current density of 10 mA cm-2, along with Tafel slope values of 68 mV
      dec-1, as well as outstanding stability in 0.5 mol L-1 H2SO4.

PMID- 29059053
TI  - Phase imaging and nanoscale energy dissipation of supported graphene using
      amplitude modulation atomic force microscopy.
AB  - We investigate the phase imaging of supported graphene using amplitude modulation
      atomic force microscopy (AFM), the so-called tapping mode. The phase contrast
      between graphene and the neighboring substrate grows in hard tapping conditions
      and the contrast is enhanced compared to the topographic one. Therefore, phase
      measurements could enable the high-contrast imaging of graphene and related two
      dimensional materials and heterostructures, which is not achievable with
      conventional AFM based topographic measurements. Obtained phase maps are then
      transformed into energy dissipation maps, which are important for graphene
      applications in various nano-mechanical systems. From a fundamental point of
      view, energy dissipation gives further insight into mechanical properties.
      Reliable measurements, obtained in the repulsive regime, show that the energy
      dissipation on a graphene-covered substrate is lower than that on a bare one, so
      graphene provides certain shielding in tip-substrate interaction. Based on the
      obtained phase curves and their derivatives, as well as on correlation
      measurements based on AFM nanoindentation and force modulation microscopy, we
      conclude that the main dissipation channels in graphene-substrate systems are
      short-range hysteresis and long-range interfacial forces.

PMID- 29059054
TI  - Correspondence model-based 4D VMAT dose simulation for analysis of local
      metastasis recurrence after extracranial SBRT.
AB  - The purpose of this study is to introduce a novel approach to incorporate patient
      specific breathing variability information into 4D dose simulation of volumetric
      arc therapy (VMAT)-based stereotactic body radiotherapy (SBRT) of extracranial
      metastases. Feasibility of the approach is illustrated by application to
      treatment planning and motion data of lung and liver metastasis patients. The
      novel 4D dose simulation approach makes use of a regression-based correspondence
      model that allows representing patient motion variability by breathing signal
      steered interpolation and extrapolation of deformable image registration motion
      fields. To predict the internal patient motion during treatment with only
      external breathing signal measurements being available, the patients' internal
      motion information and external breathing signals acquired during 4D CT imaging
      were correlated. Combining the correspondence model, patient-specific breathing
      signal measurements during treatment and time-resolved information about dose
      delivery, reconstruction of a motion variability-affected dose becomes possible.
      As a proof of concept, the proposed approach is illustrated by a retrospective 4D
      simulation of VMAT-based SBRT treatment of ten patients with 15 treated lung and
      liver metastases and known clinical endpoints for the individual metastases
      (local metastasis recurrence yes/no). Resulting 4D-simulated dose distributions
      were compared to motion-affected dose distributions estimated by standard 4D CT
      only dose accumulation and the originally (i.e. statically) planned dose
      distributions by means of GTV [Formula: see text] indices (dose to 98% of the GTV
      volume). A potential linkage of metastasis-specific endpoints to differences
      between GTV [Formula: see text] indices of planned and 4D-simulated dose
      distributions was analyzed.

PMID- 29059055
TI  - Quantum yield in polymer wrapped single walled carbon nanotubes: a computational
      model.
AB  - Quantum yield in polymer wrapped single walled carbon nanotubes (SWCNTs) has been
      computationally investigated using a 2D model of exciton decay with non-radiative
      channels due to the diffusive motion across the nanotube surface. Beside the role
      of SWCNT's ends as the exciton quenchers, we have considered the influence of the
      wrapping polymer through its chemistry and wrapping angle. The model has been
      solved exactly for zero-angle wrapping, a particular case when the polymer
      interfaces the nanotube along its axis. The general case has been treated
      numerically and it has been concluded that the wrapping angle has no relevant
      influence upon the quantum yield values which are of experimental interest. A
      wide range of quantum yield values computed in the present contribution can be
      helpful in understanding potentially available photoluminescence data of SWCNTs
      wrapped with a variety of polymer families.

PMID- 29059056
TI  - Determination of absorbed dose to water from a miniature kilovoltage x-ray source
      using a parallel-plate ionization chamber.
AB  - Electronic brachytherapy sources are widely accepted as alternatives to
      radionuclide-based systems. Yet, formal dosimetry standards for these devices to
      independently complement the dose protocol provided by the manufacturer are
      lacking. This article presents a formalism for calculating and independently
      verifying the absorbed dose to water from a kV x-ray source (The INTRABEAM
      System) measured in a water phantom with an ionization chamber calibrated in
      terms of air-kerma. This formalism uses a Monte Carlo (MC) calculated chamber
      conversion factor, [Formula: see text], to convert air-kerma in a reference beam
      to absorbed dose to water in the measurement beam. In this work [Formula: see
      text] was determined for a PTW 34013 parallel-plate ionization chamber. Our
      results show that [Formula: see text] was sensitive to the chamber plate
      separation tolerance, with differences of up to 15%. [Formula: see text] was also
      found to have a depth dependence which varied with chamber plate separation (0 to
      10% variation for the smallest and largest cavity height, over 3 to 30 mm depth).
      However for all chamber dimensions investigated, [Formula: see text] was found to
      be significantly larger than the manufacturer reported value, suggesting that the
      manufacturer recommended method of dose calculation could be underestimating the
      dose to water.

PMID- 29059057
TI  - Lateral response heterogeneity of Bragg peak ionization chambers for narrow-beam
      photon and proton dosimetry.
AB  - Large area ionization chambers (LAICs) can be used to measure output factors of
      narrow beams. Dose area product measurements are proposed as an alternative to
      central-axis point dose measurements. Using such detectors requires detailed
      information on the uniformity of the response along the sensitive area. Eight
      LAICs were investigated in this study: four of type PTW-34070 (LAICThick) and
      four of type PTW-34080 (LAICThin). Measurements were performed in an x-ray unit
      using peak voltages of 100-200 kVp and a collimated beam of 3.1 mm (FWHM). The
      LAICs were moved with a step size of 5 mm to measure the chamber response at
      lateral positions. To account for beam positions where only a fraction of the
      beam impinged within the sensitive area of the LAICs, a corrected response was
      calculated which was the basis to calculate the relative response. The impact of
      a heterogeneous LAIC response, based on the obtained response maps was henceforth
      investigated for proton pencil beams and small field photon beams. A pronounced
      heterogeneity of the responses was observed in the investigated LAICs. The
      response of LAICThick generally decreased with increasing radius, resulting in a
      response correction of up to 5%. This correction was more pronounced and more
      diverse (up to 10%) for LAICThin. Considering a proton pencil beam the systematic
      offset for reference dosimetry was 2.4-4.1% for LAICThick and  -9.5 to 9.4% for
      LAICThin. For relative dosimetry (e.g. integral depth-dose curves) systematic
      response variation by 0.8-1.9% were found. For a decreasing photon field size the
      systematic offset for absolute dose measurements showed a 2.5-4.5% overestimation
      of the response for 6  *  6 mm2 field sizes for LAICThick. For LAICThin the
      response varied even over a range of 20%. This study highlights the need for
      chamber-dependent response maps when using LAICs for absolute and relative
      dosimetry with proton pencil beams or small photon beams.

PMID- 29059058
TI  - The challenge of bimaxillary protrusion.

PMID- 29059059
TI  - Hybrid hyrax distalizer and mentoplate for rapid palatal expansion, class III
      treatment, and upper molar distalization.

PMID- 29059060
TI  - Intrusion of Maxillary Posterior Teeth to Correct a Severe Anterior Open Bite.

PMID- 29059061
TI  - Step-By-Step Traction of a Palatally Impacted Canine.

PMID- 29059062
TI  - Forsus Appliance for Treatment of Class II, Division 2 Malocclusion in Adults.

PMID- 29059063
TI  - Correction of Bimaxillary Protrusion after Extraction of Hopeless Mandibular
      Posterior Teeth and Molar Protraction.

PMID- 29059064
TI  - A Simple Glue-Tray Guide for Precise Miniscrew Insertion.

PMID- 29059065
TI  - Postmortem Vitreous Humor Magnesium Does Not Elevate in Salt Water Drowning When
      the Immersion Time Is Less Than an Hour.
AB  - BACKGROUND: Elevation in postmortem vitreous humor sodium and chloride (PMVSC) in
      salt water drowning (SWD) when the immersion time is less than 1 hour (SWD1) is
      hypothesized to result from electrolyte changes in blood from salt water
      inhalation/ingestion during drowning. After approximately 1 hour after death,
      electrolytes may diffuse into the vitreous humor via the eye coverings. Another
      abundant element in salt water is magnesium, which is approximately 50 times
      higher in concentration than the blood and vitreous humor magnesium levels.
      Magnesium is able to diffuse across the eye coverings but not as easily through
      the blood-ocular barrier. With these properties, we hypothesize that postmortem
      vitreous magnesium (PMVM) would not be elevated in SWD1 but become elevated in
      SWD with immersion times greater than 1 hour (SWD>1). AIM: The aim of this
      article was to investigate the differences in PMVM and PMVSC between nonimmersion
      deaths, SWD1, and SWD>1. METHODS: This is a 1-year retrospective study comparing
      PMVM and PMVSC in nonimmersion deaths, SWD1, and SWD>1. RESULTS: Postmortem
      vitreous magnesium is significantly higher in SWD>1 than SWD1 and nonimmersion
      deaths, with no significant difference between SWD1 and nonimmersion deaths.
      Postmortem vitreous humor sodium chloride is statistically higher in SWD1 and
      SWD>1 than nonimmersion deaths. CONCLUSIONS: As a conclusion, PMVSC elevates and
      PMVM does not elevate in SWD1.

PMID- 29059066
TI  - Transition to Cancer Survivorship: A Concept Analysis.
AB  - Transition to cancer survivorship is frequent lexicon denoting the posttreatment
      phase of cancer treatment. The concept of being in transition to survivorship is
      not well defined. To critically analyze this concept, data sources (n = 63) (from
      1985 to 2016) from nursing, sociology, medicine, and psychology were evaluated
      employing Rodgers evolutionary method. Transition to cancer survivorship is a
      turning point with a variable time period one passes through after treatment. It
      is an individualized experience with degrees of liminality, changes, and
      challenging consequences. Understanding this concept helps identify patient needs
      for targeted nursing interventions that can bridge safe passage to cancer
      survivorship.

PMID- 29059067
TI  - Former Work Life and People With Dementia.
AB  - Twelve persons with dementia were interviewed about their former work lives.
      Their motivation for choosing their past work was influenced by values of their
      contemporary culture. Those who had come to terms with their illness had positive
      feelings about their past contributions in their former paid work. However, they
      often felt that unpaid work was taken for granted and not fully recognized by
      family or society. Some wrestled with accepting their illness; they were grieving
      their losses, regardless of former success. Caregivers may use parts of work
      narratives to elevate the self-esteem and quality of life of persons with
      dementia.

PMID- 29059068
TI  - Efficacy of Armeo(r) Robotic Therapy Versus Conventional Therapy on Upper Limb
      Function in Children With Hemiplegic Cerebral Palsy.
AB  - OBJECTIVE: The aim of this study was to examine the efficacy of Armeo robotic
      therapy, compared with conventional therapy, on upper limb function in children
      with hemiplegic cerebral palsy. DESIGN: Thirty children with hemiplegic cerebral
      palsy, with ages ranging from 6 to 8 yrs, were selected for this randomized
      controlled study and randomly assigned to two groups. The study group (n = 15)
      received 12 wks of Armeo robotic therapy (45 min/session, 3 days/wk) and the
      control group (n = 15) received conventional therapy for the same period. The
      measured outcomes were the Modified Ashworth Scale and the Quality of Upper
      Extremity Skills Test, measured at baseline and after 12 wks of intervention.
      RESULTS: Children in the study group showed significant improvement in the mean
      values of all the measured variables, compared with those in the control group (P
      < 0.05). Postintervention Modified Ashworth Scale scores for the study and
      control groups were 1.6 (0.3) and 2 (0.5), respectively. Postinterventional
      Quality of Upper Extremity Skills Test total scores for the study and control
      groups were 84.6 (2.7) and 79.1 (2), respectively. CONCLUSIONS: Armeo robotic
      therapy is significantly more effective than conventional therapy in improving
      the upper limb quality of movement in children with hemiplegic cerebral palsy.

PMID- 29059069
TI  - NICU Bereavement Care and Follow-up Support for Families and Staff.
AB  - BACKGROUND: Experiencing the death of an infant in the neonatal intensive care
      unit (NICU) affects both families and staff, creating challenges and
      opportunities for best practices. PURPOSE: This practice-based article describes
      a comprehensive approach to delivering bereavement services to NICU families, as
      well as education and support to NICU staff. METHODS: Bereaved NICU parent and
      staff survey feedback, including quotes describing individual experiences and
      suggestions for improved service delivery. RESULTS: Bereaved NICU families and
      caregivers find meaning and purpose in the act of creating keepsake memories at
      the time of the infant's death. Mutual healing takes place with subsequent,
      individualized follow-up contacts by staff familiar to the bereaved parents over
      the course of a year. IMPLICATIONS FOR PRACTICE: Those staff involved in the care
      of a NICU infant and family, during and after the infant's death, attest to the
      value in providing tangible keepsakes as well as continuing their relationship
      with the bereaved parents. An effective administrative infrastructure is key to
      efficient program operations and follow-through. IMPLICATIONS FOR RESEARCH:
      Studying different methods of in-hospital and follow-up emotional support for
      NICU bereaved families. Identifying strategies for staff support during and after
      NICU infant loss, and the impact a formal program may have on staff satisfaction
      and retention.

PMID- 29059070
TI  - The evolution of antimicrobial resistance in Salmonella Typhi.
AB  - PURPOSE OF REVIEW: Increasing antimicrobial resistance in Salmonella Typhi is a
      serious public health concern, especially in industrializing countries. Here we
      review recent clinical and laboratory data concerning the evolution of
      antimicrobial resistance, with particular reference to the emergence resistance
      against fluoroquinolones, third generation cephalosporins, and azithromycin.
      RECENT FINDINGS: The last 40 years have witnessed the sequential emergence of
      resistance to all first-line antimicrobials used in the treatment of S. Typhi
      infections. Multidrug resistance (MDR), defined by resistance to chloramphenicol,
      amoxicillin, and co-trimoxazole, emerged in the 1990s, followed rapidly by
      reduced susceptibility to fluoroquinolones. In the current decade, high-level
      fluoroquinolone resistance has emerged in south Asia and threatens to spread
      worldwide. Increasing reliance is now being placed on the activity of third
      generation cephalosporins and azithromycin, but resistance against these agents
      is developing. Carbapenems and tigecycline may be alternatives, although clinical
      data are sparse, and in some settings reversion to chloramphenicol and co
      trimoxazole susceptibility is occurring. Therefore, older drugs may yet have a
      role in the treatment of S. Typhi infections. SUMMARY: Good surveillance,
      improved diagnostics, more prudent use of antimicrobials, and effective vaccines
      will all be critical to reducing the burden of disease caused by S. Typhi.

PMID- 29059071
TI  - A rational approach to the patient with hematochezia.
AB  - PURPOSE OF REVIEW: Hematochezia is a common clinical presentation, with
      significant morbidity and economic burden. These patients often require costly
      interventions including hospitalization, blood transfusions, and radiologic or
      endoscopic procedures. The purpose of this review is to give a rational, concise
      approach to the patient with hematochezia, with special consideration of recent
      advances in the literature. RECENT FINDINGS: Recent studies pertaining to
      hematochezia have evaluated risk stratification, endoscopic intervention,
      evaluation of small bowel bleeding, and management of anticoagulation. SUMMARY: A
      step-wise approach to hematochezia helps determine the cause and provide the
      appropriate management of these patients. We propose five steps beginning with
      hemodynamic assessment and risk stratification, then focused history and physical
      examination, endoscopic intervention when warranted, and consideration of small
      bowel bleeding in selected instances.

PMID- 29059072
TI  - Teaching Medical Students to Communicate With Empathy and Clarity Using
      Improvisation.
AB  - PROBLEM: Medical educators widely accept that health care providers need strong
      communication skills. The authors sought to develop a course incorporating
      improvisation to teach health professions students communication skills and build
      empathy. APPROACH: Teaching health care professionals to communicate more
      effectively with patients, the public, and each other is a goal of the Alan Alda
      Center for Communicating Science at Stony Brook University. The authors designed
      an interprofessional elective for medical, nursing, and dental students that
      differed in several respects from traditional communication training. The
      Communicating Science elective, which was offered by the Alda Center from 2012 to
      2016, used verbal and nonverbal exercises, role-playing, and storytelling,
      including improvisation exercises, to teach students to communicate with empathy
      and clarity. OUTCOMES: In course evaluations completed by 76 students in 2012 and
      2013, 100% said they would recommend the course to fellow students, saw the
      relevance of the course content to their careers, and desired more of the course
      content in their school's curriculum. As a result of this positive feedback, from
      2014 to 2016, 10 hours of instruction pairing empathy and communication training
      was embedded in the preclinical curriculum at the Stony Brook University School
      of Medicine. NEXT STEPS: This course could be an effective model, and one that
      other institutions could employ, for improving communication skills and empathy
      in the next generation of health care professionals. Next steps include
      advocating for communication skills training to be embedded throughout the
      curriculum of a four-year medical school program.

PMID- 29059073
TI  - The role of nutrition in geriatric rehabilitation.
AB  - PURPOSE OF REVIEW: To highlight the importance of nutrition in older adults
      undergoing a rehabilitation program. Geriatric rehabilitation aims at the
      recovery of physical abilities for a largely independent life in the community.
      The term 'geriatric rehabilitation' is wide and includes inpatient and ambulatory
      care as well as rehabilitation programs in hospitals, also outside geriatric
      wards. The role of nutrition is therefore not clearly defined, but an association
      between declined functional status and low nutritional status is evident. RECENT
      FINDINGS: An association has been identified between malnutrition and low
      physical function or lower rehabilitation effect, respectively. In intervention
      trials with nutritional care (additional energy or protein), a number of benefits
      for muscle mass, muscle strength, physical function, or the outcomes quality of
      life and rehospitalization were identified. In this context, the combination of
      exercise and adequate nutrition seems to be beneficial. SUMMARY: Geriatric
      patients undergoing a rehabilitation program outside inpatient, ambulatory, or
      hospitalization care need an adequate supply of energy and nutrients.
      Malnutrition must be avoided, ideally before starting rehabilitation. Nutritional
      interventions are most beneficial in combination with exercise training.

PMID- 29059074
TI  - Hereditary arrhythmias and cardiomyopathies: decision-making about genetic
      testing.
AB  - PURPOSE OF REVIEW: The modern field of clinical genetics has advanced beyond the
      traditional teachings familiar to most practicing cardiologists. Increased
      understanding of the roles of genetic testing may improve uptake and
      appropriateness of use. RECENT FINDINGS: Clinical genetics has become integral to
      the management of patients with hereditary arrhythmia and cardiomyopathy
      diagnoses. Depending on the condition, genetic testing may be useful for
      diagnosis, prognosis, treatment, family screening, and reproductive planning.
      However, genetic testing is a powerful tool with potential for underuse, overuse,
      and misuse. In the absence of a substantial body of literature on how these
      guidelines are applied in clinical practice, we use a case-based approach to
      highlight key lessons and pitfalls. Importantly, in many scenarios genetic
      testing has become the standard of care supported by numerous class I
      recommendations; genetic counselors can improve accessibility to and appropriate
      use and application of testing. SUMMARY: Optimal management of hereditary
      arrhythmias and cardiomyopathies incorporates genetic testing, applied as per
      consensus guidelines, with involvement of a multidisciplinary team.

PMID- 29059075
TI  - Extracorporeal membrane oxygenation, Berlin, and ventricular assist devices: a
      primer for the cardiologist.
AB  - PURPOSE OF REVIEW: Mechanical circulatory support (MCS) has become an
      indispensable tool in the management of children with impending respiratory and
      cardiac failure. Though extracorporeal membrane oxygenation (ECMO) was
      classically the only form of support available to pediatric patients,
      considerable advances have allowed ventricular assist devices (VADs) to become
      increasingly utilized in children. This review provides an update of recent
      advances in ECMO and VAD management in children. RECENT FINDINGS: The options for
      mechanical support in infants and small children with end-stage heart failure are
      limited. As such, the greatest advances in the past decade have come in the
      successful adoption of the Berlin Heart EXCOR device, with a marked improvement
      in survival to transplant over ECMO. Further advances have been made in the use
      of adult VADs in children. For instance, the HeartWare HVAD has been utilized in
      children as young as 3 years of age, despite being designed for use in adult
      patients. SUMMARY: The availability of mechanical support options for children
      remains limited to ECMO and a small number of VADs. While outcomes of VAD support
      in pediatric patients have been promising, further study in smaller and more
      complex pediatric patients is necessary.

PMID- 29059076
TI  - Remote monitoring of implantable cardiac devices: current state and future
      directions.
AB  - PURPOSE OF REVIEW: Recent evidence has demonstrated substantial benefits
      associated with remote monitoring of cardiac implantable electronic devices
      (CIEDs), and treatment guidelines have endorsed the use of remote monitoring.
      Familiarity with the features of remote monitoring systems and the data
      supporting its use are vital for physicians' care for patients with CEIDs. RECENT
      FINDINGS: Remote monitoring remains underutilized, but its use is expanding
      including in new practice settings including emergency departments. Patient
      experience and outcomes are positive, with earlier detection of clinical events
      such as atrial fibrillation, reductions in inappropriate implantable cardioverter
      defibrillator (ICD) shocks and potentially a decrease in mortality with frequent
      remote monitoring utilizaiton. Rates of hospitalization are reduced among remote
      monitoring users, and the replacement of outpatient follow-up visits with remote
      monitoring transmissions has been shown to be well tolerated. In addition, health
      resource utilization is lower and remote monitoring has been associated with
      considerable cost savings. A dose relationship exists between use of remote
      monitoring and patient outcomes, and those with early and high transmission rates
      have superior outcomes. SUMMARY: Remote monitoring provides clinicians with the
      ability to provide comprehensive follow-up care for patients with CIEDs. Patient
      outcomes are improved, and resource utilization is decreased with appropriate use
      of remote monitoring. Future efforts must focus on improving the utilization and
      efficiency of remote monitoring.

PMID- 29059077
TI  - The microbiome and HIV prevention strategies in women.
AB  - PURPOSE OF REVIEW: HIV prevention approaches that women can use and control are a
      priority. Results from topical and oral preexposure prophylaxis (PrEP) HIV
      prevention trials have produced inconsistent results in women. One of the main
      behavioural factors impacting effectiveness of PrEP has been suboptimal
      adherence. In this review, we examine biological factors that modulate topical
      PrEP efficacy, with particular focus on the vaginal microbiome. RECENT FINDINGS:
      Genital inflammation is an independent risk factor for HIV acquisition in women.
      Using 16S rRNA sequencing of the vaginal microbiota, anaerobic bacteria linked
      with bacterial vaginosis have been shown to be associated with both genital
      inflammation and HIV risk. Using proteomics, it was recently discovered that a
      dysbiotic vaginal microbiome, comprising less than 50% Lactobacillus spp.,
      directly influenced topical PrEP efficacy. Gardnerella vaginalis, the dominant
      vaginal species in dysbiotic women, was able to directly degrade tenofovir, but
      not dapivirine, an antiretroviral also being developed for topical PrEP. SUMMARY:
      The link between bacterial vaginosis-associated organisms with HIV risk and
      altered tenofovir gel effectiveness underscores the importance of good vaginal
      health and good adherence for women to benefit maximally from topical PrEP.
      Altering the vaginal microbiome is one of the new directions being pursued for
      HIV prevention.

PMID- 29059078
TI  - Macitentan Use in a Neurofibromatosis Type 1 Patient With Pulmonary Hypertension
      and External Jugular Phlebectasia.

PMID- 29059079
TI  - Management of Gastric Cancer With Umbilical Metastasis: A Case Report.

PMID- 29059081
TI  - The role of toll-like receptors in diabetic kidney disease.
AB  - PURPOSE OF REVIEW: Involved in innate immunity, toll-like receptors (TLRs)
      recognize pathogenic and endogenous ligands. Ligand binding initiates an
      inflammatory cascade which if sustained leads to fibrosis. This review summarizes
      the role of TLRs in diabetic kidney disease (DKD) with particular emphasis on
      TLR2 and TLR4. RECENT FINDINGS: Collectively, preclinical evidence to date
      supports the causative role of TLR2 and TLR4 in both type I and type II DKD. The
      relative importance of each is still unclear. In experimental models, there are
      increased TLR2 and TLR4 ligands, expression and signalling. Functional studies
      using inhibitors or knockout animal models confirm causality. Clinical evidence
      also supports increased ligands and TLR2 and TLR4 expression in diabetes however
      there are no clinical studies examining whether interruption of these pathways
      confer renoprotection. SUMMARY: Preclinical evidence to date supports the role of
      TLR2 and TLR4 in DKD. It will be useful to examine the value of interrupting
      these signalling pathways in clinical trials.

PMID- 29059082
TI  - Risks and management of long-term corticosteroid use in chronic rhinosinusitis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the use
      and risks of long-term corticosteroids in the management of chronic
      rhinosinusitis (CRS). RECENT FINDINGS: Long-term use of systemic corticosteroids
      is not indicated in the management of CRS due to the associated side effects and
      potential complications. Therefore, recent research has focused on the safety and
      efficacy of topical corticosteroid, particularly second-generation
      corticosteroids, and their modes of administration. Second-generation
      corticosteroids are more potent and have less systemic bioavailability than their
      first-generation counterparts. However, caution must be taken with concomitant
      use of more than two types of corticosteroids (topical, systemic, inhaled etc.)
      and also with their dosage and frequency of administration to avoid adrenal
      suppression, growth suppression in children, elevated intraocular pressure or
      epistaxis. Research is ongoing into therapies that may reduce corticosteroid
      resistance which has been demonstrated in some nasal polyps. SUMMARY:
      Corticosteroids play an essential role in the management of CRS; however, use
      must be tailored to the patient-specific disease and requires ongoing review and
      regular reevaluation by their physician.

PMID- 29059080
TI  - Leukotrienes and kidney diseases.
AB  - PURPOSE OF REVIEW: This review will critically highlight the role of leukotrienes
      as mediators of renal diseases and drug nephrotoxicity. It will also discuss the
      recently identified mechanism of cysteinyl leukotrienes induction and action, and
      will propose clinical implementation of these findings. RECENT FINDINGS: Since
      last reviewed in 1994, leukotrienes were shown to mediate drug-associated
      nephrotoxicity, transplant rejection and morbidity in several models of renal
      diseases. Although leukotrienes may be released by various infiltrating
      leukocytes, a recent study demonstrated that cytotoxic agents trigger production
      of leukotriene C4 (LTC4) in mouse kidney cells by activating a biosynthetic
      pathway based on microsomal glutathione-S-transferase 2 (MGST2). LTC4 then
      elicits nuclear accumulation of hydrogen peroxide-generating NADPH oxidase 4,
      leading to oxidative DNA damage and cell death. LTC4 inhibitors, commonly used as
      systemic asthma drugs, alleviated drug-associated damage to proximal tubular
      cells and attenuated mouse morbidity. SUMMARY: Cysteinyl leukotrienes released by
      mast cells trigger the symptoms of asthma, including bronchoconstriction and
      vasoconstriction. Therefore, effective leukotriene inhibitors were approved as
      orally administered asthma drugs. The findings that leukotrienes mediate the
      cytotoxicity of nephrotoxic drugs, and are involved in numerous renal diseases,
      suggest that such asthma drugs may ameliorate drug-induced nephrotoxicity, as
      well as some renal diseases.

PMID- 29059083
TI  - Current opinions in office-based rhinology.
AB  - PURPOSE OF REVIEW: The care of rhinologic patients has undergone a remarkable
      transformation in recent years. With the advent of endoscopic sinus surgery and
      high-tech image-guided computer systems, the surgical care of patients with
      benign sinonasal disease has successfully transitioned from the main hospital
      operating room to the outpatient ambulatory surgical center. Currently, there is
      yet another movement underway, in an attempt to care for these patients in the
      office setting. RECENT FINDINGS: As the medical device sector continues to
      innovate at rapid speed, new technologies such as the radiofrequency ablator,
      microdebrider, balloon sinus dilator, and steroid-eluting stent have propelled
      the care of rhinologic patients into the clinic setting. SUMMARY: In conjunction
      with an overall increased attention toward cost and time savings, the push to
      modernize instrumentation is now enabling the otolaryngologist to keep both the
      medical and surgical treatment of rhinologic patients, particularly those with
      chronic disease, within the office setting.

PMID- 29059084
TI  - A Qualitative Exploration of the Shift Work Experience: The Perceived Barriers
      and Facilitators to a Healthier Lifestyle and the Role of the Workplace
      Environment.
AB  - OBJECTIVES: The study aimed to understand lifestyle practices among shift
      workers, including an exploration of workers' perceptions of their workplace
      environment (WPE). METHODS: Fifteen focus groups (FGs) were conducted by two
      researchers, with a total of 109 participants. A pilot FG was carried out with
      both researchers present, to ensure consistency in facilitation. To ensure
      quality control, both researchers analyzed all data collected. RESULTS: Two
      overarching themes were observed: barriers to leading a healthier lifestyle, and
      facilitators to leading a healthier lifestyle. The influence of WPE was central
      to both themes. CONCLUSION: Investing in employee health is beneficial,
      particularly among shift workers, who are at an increased health risk. Adopting
      organizational policies and environmental changes as a core strategy for
      workplace health promotion may create an environment that makes healthier choices
      more accessible to all employees.

PMID- 29059085
TI  - Multicentric Reticulohistiocytosis: A Multicenter Case Series and Review of
      Literature.

PMID- 29059086
TI  - Rituximab for Sight-Threatening Lupus-Related Retinal Vasculitis.

PMID- 29059087
TI  - Controversies and opportunities in severe asthma.
AB  - PURPOSE OF REVIEW: Despite currently available treatments, many asthma patients
      remain inadequately controlled, but identifying distinct patient populations
      (phenotypes/endotypes) may optimize their management. This review discusses some
      of the controversies and opportunities for improved disease control in severe
      asthma. RECENT FINDINGS: Currently approved anti-immunoglobulin E and anti
      interleukin 5 biologics, which target specific pathways instead of using a 'one
      size fits all' strategy, are efficacious and well tolerated therapies for severe
      asthma. The appropriate use of these biologics, and of those in development
      (e.g., benralizumab and dupilumab), should be aided by further understanding of
      asthma phenotypes and endotypes, utilizing appropriate biomarkers.Oral
      corticosteroids are often added as maintenance therapy for patients with severe
      uncontrolled asthma, but their use is associated with significant adverse effects
      and should be considered a last option. The true cost of this therapy, including
      the cost of morbidities associated with its use, remains to be determined.Severe
      asthma in pediatrics poses a unique opportunity for possible prevention
      strategies and the potential for primary prevention. Although several avenues for
      primary prevention are being explored and are out of the scope of this review, we
      focus our discussion on the use of omalizumab, which has been recently explored
      in clinical trials. SUMMARY: Appropriate use of biologics in severe asthma should
      be supported by further understanding of biomarkers predicting response to
      targeted therapy. Because of their association with significant adverse effects,
      add-on oral corticosteroids should be considered a last treatment option for
      patients with uncontrolled severe asthma. Finally, severe asthma in pediatrics
      poses a unique opportunity for potential prevention strategies.

PMID- 29059088
TI  - Metabolomics in asthma: where do we stand?
AB  - PURPOSE OF REVIEW: Metabolomics has been used to uncover the metabolic signatures
      of asthma, both for biomarker identification and pathophysiologic mechanisms
      research. We aimed to review recent advances in this field, published since 2016,
      and discuss these findings implications to future research and application into
      clinical practice. RECENT FINDINGS: Experimental asthma models and clinical
      studies in both children and adults supported independent metabolic signatures of
      asthma. Common reported pathways included purine, glycerophospholipid,
      glutathione, fatty acids, and arginine and proline metabolism. Metabolomics-based
      studies identified candidate biomarkers related to asthma severity and
      corticosteroid resistance, and supported the definition of the obesity-related
      phenotype at the molecular level. A systematic review with meta-analysis and
      recent prospective studies favored exhaled volatile organic compounds as one of
      the most promising biomarkers in asthma diagnosis and monitoring. SUMMARY:
      Metabolomics has provided unique and novel insights into asthma profiling at the
      molecular level. Current challenges include procedures standardization and
      control of potentially confounding variables for external validation. Point-of
      care technology developments bring metabolomics closer to clinical practice. In
      addition to biomarkers identification, relating metabolites to their biologic
      role will serve as critical foundations for understanding the biology
      underpinning asthma heterogeneity and for specific-targeted therapies. VIDEO
      ABSTRACT.

PMID- 29059089
TI  - Refractory Giant Cell Arteritis Complicated by Vision Loss From Optic Atrophy and
      Maculopathy Associated With Pachymeningitis.
AB  - BACKGROUND: We describe a 75-year-old woman who experienced vision loss in her
      left eye due to biopsy-proven giant cell arteritis (GCA). She subsequently
      developed pachymeningitis causing refractory headaches and bilateral optic
      neuropathy and maculopathy. METHODS: Case report with literature review. RESULTS:
      Eighteen months after the initial diagnosis of GCA, imaging studies in our
      patient demonstrated pachymeningeal enhancement, and meningeal biopsy confirmed
      lymphoplasmacytic tissue infiltrates with low frequencies of IgG4+ plasma cells.
      Laboratory investigation revealed the presence of 3 antiretinal antibodies and
      antimyeloperoxidase antibodies, consistent with autoimmune retinopathy. Treatment
      with B-cell-depleting anti-CD20 antibodies suppressed meningeal inflammation and
      prevented further vision loss. CONCLUSIONS: This case illustrates that bilateral
      vision loss and chronic headaches in patients with GCA may result from retina
      directed autoimmunity and pachymeningitis.

PMID- 29059090
TI  - Aldosterone-to-renin ratio depends on age and sex in children attending a clinic
      for cardiovascular risk assessment.
AB  - OBJECTIVE: To determine plasma aldosterone concentration (PAC) and plasma renin
      concentration (PRC) and aldosterone-to-renin ratio (ARR) values in a population
      attending a Clinic for Cardiovascular Risk Assessment in Children. METHODS: We
      assessed ARR and associated factors in a cohort of 287 children (137 female, 4-18
      years). Weight and blood pressure (BP) were recorded. PAC (ng/dl) and PRC (mU/l)
      were measured using direct immunochemiluminescent assays. Data were examined by
      sex and according to four age classes. RESULTS: Median PAC was similar from the
      youngest to the oldest age class ranging from 7.5 to 9.9 ng/dl in males and from
      11.0 to 12.6 ng/dl in females. Median PRC was also similar across age classes in
      males ranging from 58.2 to 55.5 mU/l, whereas it progressively decreased from
      61.5 to 36.6 mU/l in females (P < 0.01). Median PRC was higher in prepubertal
      than in pubertal females only (53.6 vs. 40.2 mU/l, P < 0.03). As a result ARR was
      unchanged with increasing age in males (from 0.18 to 0.19), whereas in females it
      increased from 0.19 to 0.36 (P < 0.03). After adjusting for body weight, BP and
      other possible confounders, age was inversely related with PRC and directly with
      PAC and ARR (P < 0.001 for all), in females only. No relationship was found in
      both sexes between ARR values, BP, weight and family history of hypertension.
      CONCLUSION: In our children population, ARR is lower than in adults and diverges
      with increasing age between sexes, due to the age and puberty driven fall in PRC
      observed only in females. BP and weight are not associated with ARR distribution.

PMID- 29059091
TI  - Contact Allergy to Neem Oil.
AB  - A case of allergic contact dermatitis from neem oil is presented. Neem oil
      (synonyms: Melia azadirachta seed oil [INCI name], nim oil, margosa oil) is a
      vegetable (fixed) oil obtained from the seed of the neem tree Azadirachta indica
      by cold pressing. Contact allergy to neem oil has been described previously in
      only 3 patients. The allergen(s) is/are unknown.

PMID- 29059092
TI  - Propylene Glycol.
AB  - Propylene glycol (PG), an emollient and emulsifier found in cosmetics,
      medications, and food, has been granted the dubious honor of being named the
      American Contact Dermatitis Society's Allergen of the Year for 2018. Allergic and
      irritant contact dermatitis and systemic cutaneous reactions to PG, which has
      become an increasingly common ingredient, have been documented. Propylene glycol
      is as contentious as it is ubiquitous because it acts as both a weak sensitizer
      and an irritant, confounding the results of positive patch tests. This report
      serves to increase awareness about PG sensitization and appropriate testing and
      evaluation of PG patch tests.

PMID- 29059093
TI  - Tan in a Can: Proceed With Patch Testing.

PMID- 29059094
TI  - Sulfites: No Longer a Zebra?

PMID- 29059095
TI  - Predictors of Hospitalization, Length of Stay, and Costs of Care Among Adult and
      Pediatric Inpatients With Atopic Dermatitis in the United States.
AB  - INTRODUCTION: Little is known about the risk factors of hospitalization for
      atopic dermatitis (AD). OBJECTIVES: We sought to determine associations of
      hospitalization for AD in the United States. METHODS: Data were analyzed from the
      2002 to 2012 National Inpatient Sample. Atopic dermatitis hospitalizations were
      compared with controls, which included all hospitalizations without any diagnosis
      of AD excluding normal pregnancy/delivery, yielding a representative cohort of US
      hospitalizations. RESULTS: Both adults and children, who were admitted for AD or
      eczema, were more likely to have nonwhite race/ethnicity, lowest-quartile annual
      household income, Medicaid or no insurance, and fewer chronic conditions.
      Increased cost of care and prolonged length of stay were also associated with
      nonwhite race/ethnicities, lowest-quartile annual household income, Medicaid or
      no insurance, and having a higher number of chronic conditions. CONCLUSIONS:
      There are significant racial/ethnic and socioeconomic differences between
      patients hospitalized with AD versus without it, suggesting that there may be
      racial/ethnic and/or health care disparities in AD.

PMID- 29059096
TI  - Dermoscopic Findings of Irritant "Poral" Reactions to Cobalt During Patch
      Testing.

PMID- 29059097
TI  - Preoperative Risk Stratification of Endometrial Carcinoma: L1CAM as a Biomarker.
AB  - OBJECTIVE: Preoperative or intraoperative risk assessment models are used to
      stratify patients with endometrial carcinoma to lymphadenectomy. Our aim was to
      determine whether preoperative analysis of L1 cell adhesion molecule (L1CAM) can
      improve risk assessment. METHODS: Immunohistochemical L1CAM staining was
      performed on endometrial biopsies of 241 patients and paired hysterectomy samples
      of 75 patients. Risk assessment models based on preoperative histologic type and
      grade, myometrial invasion, and/or tumor diameter and alternative models
      incorporating preoperative L1CAM were compared with regard to their capability of
      predicting lymph nodal or distant metastasis. Soluble L1 levels were measured by
      enzyme-linked immunosorbent assay in serum samples of 40 patients with
      endometrial carcinoma. RESULTS: The concordance rate between L1CAM staining
      results of preoperative and hysterectomy samples was moderate (kappa = 0.586, P <
      0.0001). Preoperative L1CAM expression was associated with nonendometrioid
      histology, lymph node involvement, advanced stage, and positive peritoneal
      cytology. Receiver operating characteristic curve analyses showed that L1CAM did
      not significantly improve risk stratification algorithms based on traditional
      risk factors. Intraoperative tumor diameter was an effective surrogate for
      myometrial invasion. There was no statistical difference between L1 serum levels
      of patients with an L1CAM-positive or L1CAM-negative endometrial carcinoma (P =
      0.786). CONCLUSIONS: L1 cell adhesion molecule expression in endometrial biopsy
      correlates with high-risk features of endometrial carcinoma but does not
      significantly improve risk stratification algorithms based on traditional
      factors. Soluble L1 detected in the serum of patients with endometrial carcinoma
      does not correlate with tumoral L1CAM expression.

PMID- 29059098
TI  - Proliferative Melanocytic Nodule on Small Congenital Nevus During Treatment With
      Etanercept.

PMID- 29059099
TI  - Cutaneous Presentation of Mesothelioma With a Sarcomatoid Transformation.
AB  - Malignant pleural mesothelioma is a rare neoplasm of mesodermal origin. Cutaneous
      involvement of malignant pleural mesothelioma is a very rare entity, with only 11
      cases reported in the literature. Here, we describe the case of a 75-year-old man
      with stage IV epithelioid pleural mesothelioma, presenting with a cutaneous
      eruption 5 months after initial diagnosis, which revealed sarcomatoid features on
      skin biopsy. Histological analysis of malignancy progression through
      immunohistochemical staining of the pleural, lymph node, and skin tissue revealed
      gradual loss of calretinin and gain of desmin, supporting a transformation from
      epithelioid to sarcomatoid tissue. To our knowledge, this is the first reported
      case of an epithelioid to sarcomatoid transformation of malignant pleural
      mesothelioma manifesting in a cutaneous presentation.

PMID- 29059101
TI  - PREVALENCE OF POLYPOIDAL CHOROIDAL VASCULOPATHY IN WHITE PATIENTS WITH EXUDATIVE
      AGE-RELATED MACULAR DEGENERATION: Systematic Review and Meta-Analysis.
AB  - PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a disease with significant
      inter-ethnical differences. In this study, we systematically review the
      literature on the prevalence of PCV in whites referred with a diagnosis of
      exudative age-related macular degeneration (AMD). METHODS: We searched PubMed,
      Embase, the Cochrane Library, and the Web of Science on 24 March, 2017 for
      studies evaluating the prevalence of PCV in white patients with exudative AMD.
      Data extraction and risk of bias assessments were performed in duplicate. Studies
      were included for a qualitative review and a meta-analysis, including subgroup
      analysis for differences in age and sex. RESULTS: We included data from 11
      studies (>2,200 participants). For diagnosis, indocyanine green angiography was
      used together with a set of supporting criteria on fundus examination and optical
      coherence tomography. Extramacular location was more prevalent in eyes with PCV.
      Drusen was present in the fellow eye in 17% to 27%. Pooled prevalence of PCV in
      white patients with exudative AMD was 8.7% (confidence interval 95%: 7.2%-10.3%).
      Patients with PCV were 3.7 years (confidence interval 95%: 2.1 years-5.3 years)
      younger than those with other exudative AMD. Sex did not differ significantly.
      CONCLUSION: Polypoidal choroidal vasculopathy is not a rare subtype of exudative
      AMD in whites-it is present in approximately one in 11 patients.

PMID- 29059100
TI  - RESIDUAL CHOROIDAL VESSELS IN ATROPHY CAN MASQUERADE AS CHOROIDAL
      NEOVASCULARIZATION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Introducing a
      Clinical and Software Approach.
AB  - PURPOSE: To present a postprocessing approach in optical coherence tomography
      angiography (OCTA) to facilitate the visualization and interpretation of lesions
      in age-related macular degeneration with coexisting atrophy and choroidal
      neovascularization (CNV). METHODS: This retrospective study included 32 eyes of
      26 patients with atrophy and treated CNV and 8 eyes with treatment-naive
      geographic atrophy. En face optical coherence tomography slabs highlighting
      atrophy were pseudocolored and merged with the corresponding OCTA. Cross
      sectional optical coherence tomography and postprocessed OCTA were analyzed to
      identify CNV and normal choroidal vessels in relationship to the atrophy. We
      correlate the OCTA findings with those in a donor eye with treatment-naive
      geographic atrophy studied with transmission electronic microscopy. RESULTS:
      Medium-sized choroidal vessels were displaced anteriorly in areas of atrophy in
      all 40 eyes (100%), visualized in the choriocapillaris slab in all eyes, and in
      the outer retinal slab in 30 of 40 eyes (75.0%). Cross-sectional OCTA was used to
      confirm the presence of CNV. Postprocessing successfully highlighted the CNV and
      distinguished it from choroidal vessels in atrophy. Donor eye transmission
      electronic microscopy confirmed the anterior displacement of medium-sized
      choroidal vessels in geographic atrophy. CONCLUSION: The anterior displacement of
      larger choroidal vessels in atrophy requires clinician vigilance to avoid
      misinterpreting these vessels as CNV on en face OCTA. Our proposed postprocessing
      approach offers a potential solution to facilitate the interpretation of en face
      OCTA in these cases. In the absence of other tools, clinicians are encouraged to
      rely on the location of flow relative to Bruch membrane on cross-sectional OCTA
      flow images.

PMID- 29059102
TI  - Carotid Body Paraganglioma Extending to the Middle Ear Cavity.

PMID- 29059103
TI  - Prevention of kidney cancer incidence and recurrence: lifestyle, medication and
      nutrition.
AB  - PURPOSE OF REVIEW: The incidence of kidney cancer rises globally with the highest
      rates in developed countries. This demonstrates the impact of advanced diagnostic
      imaging but also rising prevalence of modifiable risk factors such as smoking,
      obesity and hypertension. A literature search was performed with focus on recent
      studies on risk factors related to lifestyle, medication and nutrition. Further
      we searched for the effect of cancer prevention strategies. RECENT FINDINGS:
      Overall, we included 76 studies of the past 5 years. Based on current evidence
      smoking tobacco, obesity and hypertension remain established risk factors for
      kidney cancer. Certain analgesics and consumption of processed meat have been
      linked to increase development of renal cell carcinoma, although data are
      limited. Fruits, fiber-rich vegetables, coffee and physical activity may have a
      protective effect against kidney cancer but causal conclusions are not yet
      supported. Significantly, there is an increasing evidence of inverse association
      between moderate alcohol consumption. SUMMARY: Overall evidence confirms an
      effective way to prevent the risk of kidney cancer is maintaining a healthy
      weight and avoid smoking. State policies should further ensure strategies to
      raise public awareness and support to adopt healthy lifestyles.

PMID- 29059104
TI  - Transfusion Strategies are Associated with Epigenetic Changes Following Blunt
      Trauma.
AB  - INTRODUCTION: Epigenetics has been identified in multiple diseases. The effect of
      transfusion strategy on epigenetics is unknown. We hypothesized that expression
      of epigenetic regulating genes would be associated with resuscitation strategy
      following blunt trauma. METHODS: Retrospective study using the inflammation in
      host response to injury (glue grant) dataset. Volume transfused over 24 h of
      packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (PLT) as well
      as crystalloids was extracted along with leucocyte microarray data of genes with
      known epigenetic modulating activity from day 1 after injury.Principal component
      analysis (PCA) was used to identify principal components (PC) within the
      transcriptomic dataset. Multiple regression associated these with volume of blood
      products and crystalloids while controlling for confounders. Genes co-expressed
      with genes central genes in the identified PCs were furthermore subjected to
      pathway analysis using the reactome database. RESULTS: PCA identified seven
      components. PRBC and crystalloid volumes were positively associated with PC1,
      implicating histone acetylation (HAT1), DNA and histone methylation (KDM6B,
      SET1DB) and histone phosphorylation (RPS6KA5). Conversely, PLT volume was
      negatively associated with PC1,5 and 6, implicating DNA methylation (DNMT1) as
      well as histone acetylation (HAT1) and phosphorylation (RPSKA3).FFP was
      negatively associated with PC3, implicating histone methylation (SETD1B) and
      phosphorylation (RPS6KA5).Co-expression network analysis identified downstream
      pathways relevant to inflammation and the innate immune response, including Toll
      like receptor, interleukin and mitogen activated protein kinase activation.
      CONCLUSIONS: Resuscitation strategy was associated with epigenetic transcriptomic
      alterations, especially for PRBC and PLT transfusions. Downstream effects may
      include pertubations of pathways involved in immune signaling and cellular
      survival.

PMID- 29059105
TI  - Recent advances in small pupil cataract surgery.
AB  - PURPOSE OF REVIEW: To highlight the existing and emerging cataract surgery trends
      in patients with insufficient mydriasis. Discuss the latest pharmacological
      approaches for pre and intraoperative pupil dilatation. Present the variety of
      newest pupil expansion devices; critically review their advantages and possible
      limitations to be considered by the surgeon. RECENT FINDINGS: The intracameral
      use of various mydriatic combinations augmenting the preoperative mydriatic
      instillations is currently gaining popularity in cataract surgery. Two main
      options are available: bolus injection of pharmacological agent or its constant
      irrigation during the phacoemulsification procedure. The former is aimed to
      expand the pupil, whereas the latter is mostly preventing the pupil from
      constriction. Introduction of femtosecond-assisted cataract surgery, apart from
      some benefits was followed by a variety of adverse effects including
      prostaglandin release into the aqueous humor causing pupil constriction.
      Preoperative administration of nonsteroidal anti-inflammatory drugs at least 1
      day prior to surgery significantly decreases the chance of pupil constriction
      after laser energy is applied to the eye. However, pupil expansion devices may be
      needed in up to 10% of cases. Following the success of the Malyugin ring
      (MicroSurgical Technology Inc., Redmond, Washington, USA) several manufacturers
      introduced pupil expansion devices of various designs. They are differing with
      materials, pupillary margin fixation mechanisms, and easiness of manipulations
      during implantation and removal. SUMMARY: Combination of proper use of pre and
      intraoperative pharmacological pupil dilatation protocols combined with pupil
      expander rings allow for well tolerated and effective cataract surgery in the
      vast majority of patients with insufficient mydriasis.

PMID- 29059106
TI  - Personality disorder and treatment outcome in alcohol use disorder.
AB  - PURPOSE OF REVIEW: As personality disorder impacts the outcome of most major
      mental disorders, it would be consistent for it to impact negatively on the
      outcome of alcohol use disorders (AUDs). This update is to provide an up-to-date
      overview of the recent literature examining the impact of personality disorder
      and personality traits on the treatment outcome of AUDs. RECENT FINDINGS:
      Comorbidity between personality disorder and AUD is significant and approaches
      50%. Patients with AUD and comorbid personality disorder are substantially less
      likely to remain in treatment, drink more per drinking day and drink more
      frequently. If retained in treatment, comorbidity does not, however, lead to
      poorer outcomes. Relapse to drinking is more common in patient with high novelty
      seeking and lower reward dependence and persistence. Reporting from most studies
      is of moderate-to-poor quality and a single high-quality study may alter these
      findings. Landmark alcohol studies are notably quiet on the impact of personality
      on AUD treatment outcome. SUMMARY: Both personality disorder and higher novelty
      seeking impact negatively on the treatment outcome of AUD. As personality
      disorder is common in this group, clinicians engaged in AUD treatment should
      screen for personality disturbance, either disorder or high novelty seeking.

PMID- 29059107
TI  - Sensor-enabled Activity Class Recognition in Preschoolers: Hip versus Wrist Data.
AB  - PURPOSE: Pattern recognition approaches to accelerometer data processing have
      emerged as viable alternatives to cut-point methods. However, few studies have
      explored the validity of pattern recognition approaches in preschoolers, and none
      have compared supervised learning algorithms trained on hip and wrist data.
      Purpose of this study was to develop, test, and compare activity class
      recognition algorithms trained on hip, wrist, and combined hip and wrist
      accelerometer data in preschoolers. METHODS: Eleven children 3-6 yr of age (mean
      age, 4.8 +/- 0.9 yr) completed 12 developmentally appropriate physical activity
      (PA) trials while wearing an ActiGraph GT3X+ accelerometer on the right hip and
      nondominant wrist. PA trials were categorized as sedentary, light activity games,
      moderate-to-vigorous games, walking, and running. Random forest (RF) and support
      vector machine (SVM) classifiers were trained using time and frequency domain
      features from the vector magnitude of the raw signal. Features were extracted
      from 15-s nonoverlapping windows. Classifier performance was evaluated using
      leave-one-out cross-validation. RESULTS: Cross-validation accuracy for the hip,
      wrist, and combined hip and wrist RF models was 0.80 (95% confidence interval
      (CI), 0.79-0.82), 0.78 (95% CI, 0.77-0.80), and 0.82 (95% CI, 0.80-0.83),
      respectively. Accuracy for hip, wrist, and combined hip and wrist SVM models was
      0.81 (95% CI, 0.80-0.83), 0.80 (95% CI, 0.79-0.80), and 0.85 (95% CI, 0.84-0.86),
      respectively. Recognition accuracy was consistently excellent for sedentary
      (>90%); moderate for light activity games, moderate-to-vigorous games, and
      running (69%-79%); and modest for walking (61%-71%). CONCLUSIONS: Machine
      learning algorithms such as RF and SVM are useful for predicting PA class from
      accelerometer data collected in preschool children. Although classifiers trained
      on hip or wrist data provided acceptable recognition accuracy, the combination of
      hip and wrist accelerometer delivered better performance.

PMID- 29059108
TI  - Neuromuscular Electrical Stimulation Superimposed on Movement Early after ACL
      Surgery.
AB  - PURPOSE: Quadriceps weakness and asymmetrical loading of lower limbs are two
      major issues after anterior cruciate ligament reconstruction (ACLR). The aim of
      this study was to evaluate the effectiveness of a 6-wk training protocol
      involving neuromuscular electrical stimulations (NMES) of the quadriceps muscle
      superimposed on repeated sit-to-stand-to-sit exercises (STSTS), as an additional
      treatment to standard rehabilitation, from the 15th to the 60th day after ACLR.
      METHODS: Sixty-three ACLR patients were randomly allocated to one of the three
      treatment groups: NMES superimposed on STSTS (NMES + STSTS), STSTS only, or no
      additional treatment (NAT) to standard rehabilitation. Maximal isometric strength
      of the knee extensor and flexor muscles was measured 60 and 180 d after surgery.
      Asymmetry in lower extremity loading was measured during a sit-to-stand movement
      at 15, 30, 60, and 180 d after surgery and during a countermovement jump 180 d
      after surgery by means of two adjacent force platforms placed under each foot.
      RESULTS: The NMES + STSTS participants showed higher muscle strength of the knee
      extensors, which was accompanied by lower perception of pain and higher symmetry
      in lower extremity loading compared with STSTS-only and NAT participants after
      both 60 and 180 d from surgery. Participants in the STSTS-only treatment group
      showed higher symmetry in lower extremity loading compared with those in the NAT
      group 60 d after surgery. CONCLUSIONS: These results suggest that an early
      intervention based on NMES superimposed to repeated STSTS exercises is effective
      for recovering quadriceps strength and symmetry in lower extremity loading by the
      time of return to sport.

PMID- 29059109
TI  - Metabolic Bone Diseases and Total Hip Arthroplasty: Preventing Complications.
AB  - Metabolic bone diseases are a diverse group of conditions characterized by
      abnormalities in calcium metabolism and/or bone cell physiology. These unbalanced
      processes can eventually lead to bony deformities and altered joint biomechanics,
      resulting in degenerative joint disease. Not infrequently, patients with
      metabolic bone diseases have restricting hip joint pain that ultimately
      necessitates hip arthroplasty. To minimize complications, the surgeon must
      consider the particular characteristics of these patients. The surgical and
      medical management of patients with metabolic bone diseases undergoing hip
      arthroplasty requires appropriate preoperative diagnosis, careful attention to
      the technical challenges of surgery, and strategies to maximize the long-term
      results of the surgical intervention, such as the use of bone anabolic and
      anticatabolic agents.

PMID- 29059110
TI  - Discoid Lateral Meniscus in Children: Diagnosis, Management, and Outcomes.
AB  - Discoid meniscus is a congenital variant of the knee joint that typically
      involves abnormal morphology and potential instability of the lateral meniscus.
      Some discoid menisci have abnormal peripheral attachments and are unstable.
      Discoid menisci are prone to tearing secondary to increased thickness, poor
      tissue quality, and instability. Patients may or may not be symptomatic. Torn or
      unstable discoid menisci cause mechanical symptoms, pain, and swelling.
      Symptomatic patients in whom nonsurgical management fails most frequently are
      treated with arthroscopic surgery. Historically, complete meniscectomy has
      successfully alleviated symptoms but has resulted in poor midterm results, with
      degenerative changes to the knee joint. Current treatment emphasizes the
      saucerization of the meniscus, with removal of the central disk and retention of
      the peripheral crescent. Peripheral meniscal repair is performed when instability
      is present. Short-term results are good; however, degenerative changes have been
      reported at intermediate follow-up.

PMID- 29059111
TI  - Pedicled Rotational Medial and Lateral Gastrocnemius Flaps: Surgical Technique.
AB  - Gastrocnemius flaps have been used for decades to reconstruct defects of the
      proximal tibia and knee. They have proven to be useful in the soft-tissue
      reconstruction of defects caused by trauma, tumors, and infections about the
      knee, and the reconstruction of extensor mechanism discontinuity with and without
      total joint arthroplasty. The flaps have low failure rates and a distinct
      proximally based blood supply that allows them to be elevated and rotated up to
      15 cm above the level of the knee joint. The vascular anatomy is reproducible
      because rotational flaps do not require microvascular anastomosis. An
      understanding of the applied surgical anatomy, approaches, and utility of the
      gastrocnemius flap makes the technique a useful tool for the orthopaedic surgeon
      when plastic surgery assistance is not readily available.

PMID- 29059112
TI  - The Posteromedial Corner of the Knee: Anatomy, Pathology, and Management
      Strategies.
AB  - The posteromedial corner of the knee encompasses five medial structures posterior
      to the medial collateral ligament. With modern MRI systems, these structures are
      readily identified and can be appreciated in the context of multiligamentous knee
      injuries. It is recognized that anteromedial rotatory instability results from an
      injury that involves both the medial collateral ligament and the posterior
      oblique ligament. Like posterolateral corner injuries, untreated or concurrent
      posteromedial corner injuries resulting in rotatory instability place additional
      strain on anterior and posterior cruciate ligament reconstructions, which can
      ultimately contribute to graft failure and poor clinical outcomes. Various
      options exist for posteromedial corner reconstruction, with early results
      indicating that anatomic reconstruction can restore valgus stability and improve
      patient function. A thorough understanding of the anatomy, physical examination
      findings, and imaging characteristics will aid the physician in the management of
      these injuries.

PMID- 29059113
TI  - The Diagnostic Utility of Synovial Fluid Markers in Periprosthetic Joint
      Infection: A Systematic Review and Meta-analysis.
AB  - INTRODUCTION: This study is a systematic review of all reported synovial fluid
      markers for the diagnosis of periprosthetic joint infection and a meta-analysis
      of the most frequently reported markers to identify those of greatest diagnostic
      utility. METHODS: A search of six databases was conducted to identify all studies
      evaluating the utility of synovial fluid markers in the diagnosis of
      periprosthetic joint infection. Two observers assessed methodologic quality and
      extracted data independently. A meta-analysis of the most frequently reported
      markers was performed. RESULTS: Twenty-three studies were included in the meta
      analysis. The most common markers (and their respective area under the curve)
      were interleukin-17 (0.974), leukocyte esterase (0.968), alpha-defensin (0.958),
      interleukin-6 (0.956), interleukin-1beta (0.948), and C-reactive protein (0.927).
      Among these markers, alpha-defensin had the highest diagnostic odds ratio but did
      not achieve statistically significant superiority. CONCLUSION: The most
      frequently studied synovial fluid markers for the diagnosis of periprosthetic
      joint infection are C-reactive protein, leukocyte esterase, interleukin-6,
      interleukin-1beta, alpha-defensin, and interleukin-17, all of which have high
      diagnostic utility. LEVEL OF EVIDENCE: Level II.

PMID- 29059114
TI  - Findings Associated With Knee Pathology on MRI in Patients Without
      Osteoarthritis.
AB  - INTRODUCTION: We conducted a retrospective study in patients with minimal or no
      radiographically evident knee osteoarthritis to determine whether presenting
      signs and symptoms were predictive of knee pathology that was evident on MRI and
      could be treated with nonarthroplasty knee surgery or could alter nonsurgical
      treatment. METHODS: We reviewed records of patients for whom sports medicine
      orthopaedic surgeons had ordered an MRI of the knee. Univariate analysis
      identified factors that were associated with positive MRI findings (eg,
      surgically treatable lesion, meniscal tear) or a finding that could alter
      treatment. We used multivariate logistic regression to determine independent
      predictors of evidence of pathology on MRI. RESULTS: Of the 434 patients in the
      study, 281 (64.7%) had evidence of knee pathology on MRI. Acute injury, effusion,
      and ligamentous instability were among the independent predictors of positive MRI
      results. Patients with evidence of knee pathology on MRI were more likely to have
      undergone surgery. DISCUSSION: Specific aspects of patient history and physical
      examination are associated with evidence of knee pathology on MRI. CONCLUSIONS:
      In patients without osteoarthritis, positive findings on knee MRI could be
      associated with a number of presenting signs and symptoms, and this information
      could aid physicians in deciding which patients should undergo knee MRIs.
      Additional prospective research is needed to validate the relationships
      discovered in our study. LEVEL OF EVIDENCE: Level III retrospective study.

PMID- 29059115
TI  - Using Lean Process Improvement to Enhance Safety and Value in Orthopaedic
      Surgery: The Case of Spine Surgery.
AB  - Lean methodology was developed in the manufacturing industry to increase output
      and decrease costs. These labor organization methods have become the mainstay of
      major manufacturing companies worldwide. Lean methods involve continuous process
      improvement through the systematic elimination of waste, prevention of mistakes,
      and empowerment of workers to make changes. Because of the profit and
      productivity gains made in the manufacturing arena using lean methods, several
      healthcare organizations have adopted lean methodologies for patient care. Lean
      methods have now been implemented in many areas of health care. In orthopaedic
      surgery, lean methods have been applied to reduce complication rates and create a
      culture of continuous improvement. A step-by-step guide based on our experience
      can help surgeons use lean methods in practice. Surgeons and hospital centers
      well versed in lean methodology will be poised to reduce complications, improve
      patient outcomes, and optimize cost/benefit ratios for patient care.

PMID- 29059116
TI  - Management of Failed Rotator Cuff Repair in Young Patients.
AB  - Management of failed rotator cuff repair may be difficult, especially in young
      patients. Various nonmodifiable and modifiable patient factors, including age,
      tendon quality, rotator cuff tear characteristics, acute or chronic rotator cuff
      tear, bone quality, tobacco use, and medications, affect rotator cuff repair
      healing. Surgical variables, such as the technique, timing, tension on the
      repair, the biomechanical construct, and fixation, as well as the postoperative
      rehabilitation strategy also affect rotator cuff repair healing. Variable
      outcomes have been reported in patients who undergo revision rotator cuff repair;
      however, a systematic surgical approach may increase the likelihood of a
      successful outcome. Numerous cellular and mechanical biologic augments, including
      platelet-rich plasma, platelet-rich fibrin matrix, mesenchymal stem cells, and
      acellular dermal matrix grafts, have been used in rotator cuff repair; however,
      conflicting or inconclusive outcomes have been reported in patients who undergo
      revision rotator cuff repair with the use of these augments. A variety of tendon
      transfer options, including latissimus dorsi, teres major, lower trapezius,
      pectoralis minor, pectoralis major, combined pectoralis major and latissimus
      dorsi, and combined latissimus dorsi and teres major, are available for the
      management of massive irreparable rotator cuff tears. Ultimately, the
      optimization of surgical techniques and the use of appropriate biologic/tendon
      transfer techniques, if indicated, is the best method for the management of
      failed rotator cuff repair.

PMID- 29059117
TI  - Reconstruction Following Tumor Resections in Skeletally Immature Patients.

PMID- 29059118
TI  - Early haemorrhage control and management of trauma-induced coagulopathy: the
      importance of goal-directed therapy.
AB  - PURPOSE OF REVIEW: The aim of this study was to discuss the recent developments
      in trauma-induced coagulopathy and the evolvement of goal-directed therapy.
      RECENT FINDINGS: Mortality from major trauma continues to be a worldwide problem,
      and massive haemorrhage remains a major cause in 40% of potentially preventable
      trauma deaths. Development of trauma-induced coagulopathy challenges 25-35% of
      the patients further increasing trauma mortality. The pathophysiology of
      coagulopathy in trauma reflects at least two distinct mechanisms: Acute traumatic
      coagulopathy, consisting of endogenous heparinization, activation of the protein
      C pathway, hyperfibrinolysis and platelet dysfunction, and resuscitation
      associated coagulopathy. Clear fluid resuscitation with crystalloids and colloids
      is associated with dilutional coagulopathy and poor outcome in trauma.
      Haemostatic resuscitation is now the backbone of trauma resuscitation using a
      ratio-driven strategy aiming at 1:1:1 of red blood cells, plasma and platelets
      while applying goal-directed therapy early and repeatedly to control trauma
      induced coagulopathy. SUMMARY: Trauma resuscitation should focus on early goal
      directed therapy with use of viscoelastic haemostatic assays while initially
      applying a ratio 1:1:1 driven transfusion therapy (with red blood cells, plasma
      and platelets) in order to sustain normal haemostasis and control further
      bleeding.

PMID- 29059119
TI  - Early management of acute cerebrovascular accident.
AB  - PURPOSE OF REVIEW: Stroke is common and often presents as a neurologic emergency
      that requires rapid evaluation and treatment to minimize debilitation. Recent
      advances in therapy expanded time windows for intra-arterial thrombectomy in
      ischemic stroke, and surgical interventions for clot evacuation in large
      intracranial hemorrhage have recently proven feasible. This review discusses
      recent data regarding new therapeutic options in both ischemic and hemorrhagic
      stroke, notably in scenarios in which therapy was previously limited to
      supportive care. RECENT FINDINGS: Recent data show that intra-arterial therapy in
      ischemic stroke provides both benefit in outcomes and potential for further
      advancements in care. Therapeutic windows for endovascular treatment of a
      cerebral vessel occlusion now extend to 6 h, and recent data suggest this may
      increase further to 24 h. Intervention in hemorrhagic stroke remains limited to
      reversal of coagulopathy and hypertension; however, surgical techniques are
      underway and may prove beneficial in some cases. SUMMARY: Advancing therapeutics
      in ischemic and hemorrhagic stroke are changing acute care intervention and
      broadening potential candidates for what were once thought to be nonintervenable
      conditions. Execution of best practices in stroke will continue to evolve and
      will require understanding advanced imaging techniques, as well as selection
      criteria for procedural and surgical interventions.

PMID- 29059120
TI  - Change in Depression, Confidence, and Physical Function Among Older Adults With
      Mild Cognitive Impairment.
AB  - BACKGROUND AND PURPOSE: Nearly a quarter of those in the United States older than
      71 years experience mild cognitive impairment. Persons with mild cognitive
      impairment battle depression and progressive disengagement from daily activities,
      which contribute to participation restriction and activity limitation. Daily
      engagement in meaningful activity (DEMA) is a tailored intervention designed to
      benefit persons with mild cognitive impairment and their caregivers through
      preserved engagement and supported adjustment to cognitive changes. This
      secondary analysis was guided by the International Classification of Functioning,
      Disability and Health (ICF) model. Aims were to (i) explore the extent to which
      change in self-rated activity performance and physical function can predict
      change in depressive symptoms, (ii) evaluate for difference in confidence and
      depressive symptoms at ICF levels of activity and participation, and (iii)
      quantify the impact of daily engagement at the ICF level of participation on
      physical function. METHODS: A secondary analysis was conducted using data from
      the parent study, which was a 2-group randomized trial involving persons with
      mild cognitive impairment and their informal caregivers participating in the
      Indiana Alzheimer Disease Center DEMA program. Quantitative analysis (dyads: DEMA
      N = 20, Information Support N = 20) examined outcomes at posttest and follow-up.
      Analysis employed linear regression to model the relationship between explanatory
      and dependent variables and independent t test to examine for difference in
      confidence, depression, and physical function. RESULTS AND DISCUSSION: At
      posttest, change in self-rated performance predicted change in depressive
      symptoms. Those in the DEMA group who engaged in activity at the ICF level of
      participation demonstrated a significant increase in confidence and physical
      function. Although not significant, the control group posttest results showed a
      mean decrease in confidence. CONCLUSIONS: Results demonstrate a positive impact
      of DEMA on depressive symptoms, confidence, and physical function. Change in
      occupational performance predicted change in depressive symptoms. Confidence
      significantly improved among those who engaged at the ICF participation level. A
      larger, randomized controlled longitudinal trial is needed to better assess the
      impact of DEMA on physical function, activity, participation restriction, and
      quality of life.

PMID- 29059121
TI  - Reliability and Validity of the Floor Transfer Test as a Measure of Readiness for
      Independent Living Among Older Adults.
AB  - BACKGROUND AND PURPOSE: The ability to get up from the floor after a fall is a
      basic skill required for functional independence. Consequently, the inability to
      safely get down and up from the floor or to perform a floor transfer (FT) may
      indicate decreased mobility and/or increased frailty. A reliable and valid test
      of FT ability is a critical part of the clinical decision-making process. The FT
      test is a simple, performance-based test that can be administered quickly and
      easily to determine a patient's ability to safely and successfully get down and
      up from the floor using any movement strategy and without time restriction. The
      primary purpose of this cross-sectional study was to determine the intrarater
      reliability and validity of the FT test as a practical alternative to several
      widely used yet time-consuming measures of physical disability, frailty, and
      functional mobility. METHODS: A total of 61 community-dwelling older adults (65
      96 years of age) participated in the study divided into 2 separate subsamples: 15
      of them in the intrarater reliability part, while the other 46 in the concurrent
      validity one. In both subsamples, the participants were stratified on the basis
      of the self-reported levels of FT ability as independent, assisted, and
      dependent. Intrarater reliability was assessed in 2 separate occasions and scores
      were analyzed by intraclass correlation coefficient and kappa statistics.
      Concurrent validity of the FT test was assessed against the self-reported FT
      ability questionnaire, Physical Functioning Scale, Phenotype of Physical Frailty,
      and the Short Physical Performance Battery. Known-groups validity was tested by
      determining whether the FT test distinguished between (1) community-dwelling
      older adults with physical disabilities versus those who without physical
      disabilities; and (2) community-dwelling older adults who were functionally
      dependent versus those who were independent. Participants were also categorized
      on the basis of FT test outcome as independent, assisted, or dependent. The
      Spearman correlation coefficients were calculated to examine the strength of the
      relationships between the FT test and physical status measures. The Kruskal
      Wallis test was used to determine whether the FT test significantly discriminated
      between groups as categorized by the Physical Functioning Scale and Short
      Physical Performance Battery, and to examine the significance level of the
      sociodemographic data across the 3 FT test outcome groups. RESULTS: The
      intrarater reliabilities of the measures were good (0.73-1.00). There were
      statistically positive and strong correlations between the FT test and all
      physical status measures (rho ranged from 0.86 to 0.93, P < .001). Older adults
      who passed the FT test were collectively categorized as those without physical
      disabilities and functionally independent, whereas older adults who failed the FT
      test were categorized as those with physical disabilities and functionally
      dependent (P < .001). CONCLUSION: The FT test is a reliable and valid measure for
      screening for physical disability, frailty, and functional mobility. It can
      determine which older adults have physical disabilities and/or functional
      dependence and hence may be useful in assessing readiness for independent living.
      Inclusion of the FT test at initial evaluation may reveal the presence of these
      conditions and address the safety of older adults in the community.

PMID- 29059122
TI  - Response to the Letters Regarding the North American Society of Pediatric
      Gastroenterology, Hepatology and Nutrition NAFLD Guidelines.

PMID- 29059123
TI  - Implant Density at the Apex Is More Important Than Overall Implant Density for 3D
      Correction in Thoracic Adolescent Idiopathic Scoliosis Using Rod Derotation and
      En Bloc Vertebral Derotation Technique.
AB  - STUDY DESIGN: Biomechanical analysis of 3D correction and bone-screw forces
      through numerical simulations of scoliosis instrumentation with different pedicle
      screw patterns. OBJECTIVE: To analyze the effect of different screw densities and
      distributions on 3D correction and bone-screw forces in adolescent idiopathic
      scoliosis (AIS) instrumentation. SUMMARY OF BACKGROUND DATA: Instrumentation
      constructs with various numbers of pedicle screws and patterns have been proposed
      for thoracic AIS instrumentation. However, systematic biomechanical studies have
      not yet been completed on the appropriate screw patterns for optimal 3D
      correction. METHODS: Patient-specific biomechanical models of the spine were
      created for 10 AIS cases (Lenke 1). For each case, surgical instrumentation
      patterns were computationally simulated using respectively a reference screw
      pattern (two screws per level fused) and six alternative screw patterns with
      fewer screws. Simulated surgical maneuvers and model definition were unchanged
      between simulations except the number and distribution of screws. 3D correction
      and bone-screw forces were compared. RESULTS: A total of 140 posterior
      instrumentations were computationally simulated. Mean corrections in the coronal
      and sagittal planes with alternative screw patterns were within 4 degrees  to the
      reference pattern. Increasing screw density in the apical region from one to two
      screws per level improved percent apical vertebral rotation (AVR) correction (r =
      0.887, P < 0.05). Average bone-screw force associated with the reference screw
      pattern was 243N +/- 54N and those with the alternative screw patterns were 11%
      to 48% lower. CONCLUSION: Compared with the reference maximal screw density
      pattern, alternative screw patterns allowed similar corrections in the coronal
      and sagittal planes. AVR correction was strongly correlated with screw density in
      the apical region; AVR correction varied significantly with screw patterns of the
      same overall screw density when an en bloc vertebral derotation technique was
      simulated. High screw density tended to overconstrain the instrumented spine and
      resulted in higher forces at the bone-screw interface. LEVEL OF EVIDENCE: N/A.

PMID- 29059125
TI  - In View: Research Highlights.

PMID- 29059126
TI  - Ginny L. Bumgardner, MD, PhD.

PMID- 29059127
TI  - Organ Donation in the Era of the Opioid Crisis: A Clinical Strategy to Maximize
      Transplantation.

PMID- 29059128
TI  - The 2017 Transplantation Awards: Recognizing a Landmark Clinical Trial and a
      Basic Science Discovery With Far-Reaching Implications.

PMID- 29059129
TI  - Expanding the Toolkit for the Study of Allospecific B and T Cell Responses.

PMID- 29059130
TI  - The Authors' Reply.

PMID- 29059131
TI  - The Author's Reply.

PMID- 29059132
TI  - Medical Cannabis in Parkinson Disease: Real-Life Patients' Experience.
AB  - BACKGROUND: The use of medical cannabis (MC) is controversial. Support for its
      benefits is based on small clinical series. OBJECTIVE: The aim of this study was
      to report the results of a standardized interview study that retrospectively
      assessed the effects of MC on symptoms of Parkinson disease (PD) and its adverse
      effects in patients treated for at least 3 months. METHODS: The survey used
      telephone interviews using a structured questionnaire based on subjective global
      impressions of change for various parkinsonian symptoms and yes/no questions on
      adverse effects. RESULTS: Forty-seven nondemented patients with PD (40 men)
      participated. Their mean age was 64.2 +/- 10.8 years, mean disease duration was
      10.8 +/- 8.3 years, median Hoehn and Yahr (H&Y) was stage III. The duration of MC
      use was 19.1 +/- 17.0 months, and the mean daily dose was 0.9 +/- 0.5 g. The
      delivery of MC was mainly by smoking cigarettes (38 cases, 80.9%). Effect size
      (r) improvement for falls was 0.89, 0.73 for pain relief, 0.64 for depression,
      0.64 for tremor, 0.62 for muscle stiffness, and 0.60 for sleep. The most
      frequently reported adverse effects from MC were cough (34.9%) in those who used
      MC by smoking and confusion and hallucinations (reported by 17% each) causing 5
      patients (10.6%) to stop treatment. CONCLUSIONS: Medical cannabis was found to
      improve symptoms of PD in the initial stages of treatment and did not cause major
      adverse effects in this pilot, 2-center, retrospective survey. The extent of use
      and the reported effects lend support to further development of safer and more
      effective drugs derived from Cannabis sativa.

PMID- 29059133
TI  - A Phase Ib Randomized Controlled Study to Evaluate the Effectiveness of a Single
      Dose of the NR2B Selective N-Methyl-D-Aspartate Antagonist MK-0657 on Levodopa
      Induced Dyskinesias and Motor Symptoms in Patients With Parkinson Disease.
AB  - OBJECTIVES: Blockade of N-methyl-D-aspartate receptors containing the NR2B
      subunit has been shown to be therapeutic in animal models of Parkinson disease
      (PD). However, findings with investigational NR2B receptor antagonists in PD
      patients have been mixed. The objective of this study was to evaluate the effects
      of the NR2B selective N-methyl-D-aspartate receptor antagonist MK-0657 on
      levodopa-induced dyskinesias and motor symptoms in PD patients. METHODS: A
      randomized, double-blind, single-dose, 2-period crossover study was conducted in
      22 patients with PD and levodopa-induced peak-dose dyskinesias. Patients received
      oral MK-0657 (7 mg) or placebo, in randomized order, on each of 2 test days. On
      both days, levodopa was administered as a 2-hour intravenous infusion at greater
      than or equal to 1 mg/kg per hour with frequent assessments of dyskinesia, motor
      function, and pharmacokinetics. RESULTS: MK-0657 7 mg had no significant effect
      on dyskinesias (difference versus placebo in modified Abnormal Involuntary
      Movement Scale mean change from baseline area under the curve over 5 hours, -2.3;
      95% confidence interval, -5.1 to 0.4) or motor function (difference versus
      placebo in Unified Parkinson's Disease Rating Scale Part III mean change from
      baseline area under the curve over 5 hours, 13.9; 95% confidence interval, -1.7
      to 29.5). MK-0657 7 mg achieved the target mean maximum plasma concentration of
      400 nM. CONCLUSIONS: These data suggest that a single dose of MK-0657 7 mg is not
      effective in improving levodopa-induced dyskinesias and motor symptoms in PD
      patients. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT00505843.

PMID- 29059134
TI  - Aripiprazole for Post-traumatic Stress Disorder: A Systematic Review.
AB  - OBJECTIVE: The aim of this study was to review the safety and efficacy of
      aripiprazole as monotherapy and adjunct therapy for the treatment of post
      traumatic stress disorder (PTSD). METHODS: A search of both MEDLINE (1956 to May
      2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole"
      and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD."
      Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole
      as monotherapy or adjunct therapy were analyzed for relevance. Those that met the
      objective of this study were included for evaluation: 1 placebo-controlled trial;
      4 open-label trials; and 1 retrospective chart review. RESULTS: In patients with
      a history of PTSD, aripiprazole resulted in significant improvements in the
      primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD
      Checklist-Military scores, in all but 1 study analyzed. Study durations ranged
      from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily
      that could be titrated up or down in the range of 2 to 30 mg daily based on
      efficacy and tolerability. Overall, aripiprazole was well tolerated with the most
      common treatment-related study discontinuations attributed to the adverse events
      of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence.
      CONCLUSIONS: Based on the reviewed literature, aripiprazole is a reasonable
      therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger
      randomized controlled trials are needed to better understand the role of this
      atypical antipsychotic in patients with PTSD.

PMID- 29059135
TI  - Pramipexole and Electroconvulsive Therapy in Treatment-Resistant Depression.
AB  - BACKGROUND: Major depressive disorder (MDD) is a common disease. Despite
      appropriate antidepressant treatment, approximately one third of patients do not
      achieve adequate response. In these patients, electroconvulsive therapy (ECT) is
      a possible option. Nevertheless, some symptoms may persist even after ECT.
      METHOD: This is a comparative retrospective study assessing the efficacy and
      safety of pramipexole in the treatment of resistant depression, in combination to
      ECT or after a partial ECT efficacy. RESULTS: We recruited 14 patients with
      severe MDD. Nine patients received ECT and pramipexole conjointly, the latter
      being introduced after a mean number of 18 ECT sessions. Five patients received
      pramipexole after failure of ECT. Montgomery-Asberg Depression Rating Scale and
      Clinical Global Impression scores all improved significantly after the initiation
      of pramipexole (jointly with ECT or alone). Moreover, the combination of ECT plus
      pramipexole was well tolerated. Only 1 patient presented a hypomanic episode,
      which resolved spontaneously. CONCLUSIONS: Pramipexole is a therapeutic option
      for MDD resistant to ECT. It could be used jointly to ECT or after a partial
      remission with ECT. More studies are needed to precisely describe the optimal
      combination of sequential use of ECT and pramipexole in treatment-resistant MDD.

PMID- 29059136
TI  - Successful Use of Escitalopram for the Treatment of Visual Hallucinations in
      Patients With Parkinson Disease.
AB  - INTRODUCTION: Patients with Parkinson disease (PD) frequently experience visual
      hallucinations (VH). Visual hallucinations are most often viewed as an adverse
      effect of antiparkinsonian treatment. Possible treatments for this disturbance
      include a reduction of antiparkinsonian medications, adding atypical
      antipsychotics, or cholinesterase inhibitors. Some studies demonstrated that
      selective serotonin reuptake inhibitors may be an optional treatment for patients
      experiencing psychosis or agitation in dementia. Currently, there is no standard
      recommended treatment for VH in patients with PD. We present here our clinical
      experience with escitalopram (selective serotonin reuptake inhibitor) for
      treating this disturbance. METHODS: Thirteen patients with PD (8 men and 5 women;
      age range 67-83 years) experiencing VH were openly treated with escitalopram 10
      or 15 mg/d as add-on. Efficacy was assessed at baseline, then after 4 and 8 weeks
      of treatment using Clinical Global Impression-Severity and Clinical Global
      Impression-Improvement. RESULTS: At the end of the 4th week of treatment, of 13
      patients, 11 subjects demonstrated improvement, and in only 2 patients were there
      no changes in their condition. After an additional 4 weeks, 2 of the responders
      showed very significant improvement, 6 demonstrated much improvement, and 3
      patients demonstrated minimal improvement. Only 1 patient showed no change in his
      condition. One additional patient stopped taking escitalopram after 5 weeks
      because of an absence of improvement in his state. CONCLUSIONS: Escitalopram was
      well tolerated as treatment of VH in PD patients. This medication could be a
      promising optional therapy for this disturbance; however, further randomized
      controlled and bigger studies are necessary.

PMID- 29059137
TI  - Cohesion of Hyaluronic Acid Fillers: Correlation Between Cohesion and Other
      Physicochemical Properties.
AB  - BACKGROUND: There are several published articles on characterization of fillers,
      describing methods for both chemical and physicochemical characterization.
      Recently a lot of focus has been on the development of methods for measuring
      cohesion of hyaluronic acid (HA) fillers. OBJECTIVE: The aim of this study is to
      investigate and compare the drop-weight method and the correlation between
      cohesion and other physicochemical properties using a variety of HA fillers.
      MATERIALS AND METHODS: HA fillers covering several product families and
      manufacturing techniques were used. The HA fillers also covered a range of HA
      concentrations from 12 to 24 mg/mL. Cohesion was determined using sensory
      evaluation and the drop-weight method. Other physicochemical properties evaluated
      were rheology and the swelling factor. RESULTS: In this study, it was verified
      that values obtained by the drop-weight method reflect the perceived cohesion
      very well. The correlation with rheology is affected by the HA concentration in
      the products. A remarkably good correlation between swelling factor and cohesion
      was found. CONCLUSION: Cohesion correlates with other physicochemical methods. It
      could be discussed whether there is a need for a separate cohesion method because
      other already established physicochemical methods such as rheology and swelling
      factor can describe the underlying properties that affect cohesion.

PMID- 29059138
TI  - Repair of a Large Dorsal Hand Defect With Exposed Tendons.

PMID- 29059139
TI  - Hyaluronic Acid Gel With (HARRL) and Without Lidocaine (HAJU) for the Treatment
      of Moderate-to-Severe Nasolabial Folds: A Randomized, Evaluator-Blinded, Phase
      III Study.
AB  - BACKGROUND: Hyaluronic acid (HA) dermal fillers are frequently used to correct or
      smooth facial wrinkles and folds such as nasolabial folds. OBJECTIVE: To compare
      the efficacy and safety of 2 HA gels, formulated by 2 different manufacturing
      processes: XpresHAn Technology (HARRL [with lidocaine]) and Hylacross technology
      (HAJU-a comparator product without lidocaine). PATIENTS AND METHODS: One hundred
      seventy subjects with bilateral nasolabial folds rated as moderate or severe,
      according to the Wrinkle Severity Rating Scale (WSRS), received injections of
      HARRL in the nasolabial folds on one side of the face and HAJU on the other side.
      Investigator- and subject-assessed wrinkle severity was measured up to 48 weeks
      after final injection. RESULTS: HARRL exhibited a similar safety and efficacy
      profile compared with HAJU. Noninferiority of HARRL was demonstrated at 24 weeks
      (WSRS mean change from baseline mean difference -0.1 [95% confidence interval: 
      0.15, 0.01], p = .090). Incidence of adverse events was 40% for both treatments.
      CONCLUSION: HARRL exhibited a similar safety and efficacy profile compared with
      HAJU.

PMID- 29059140
TI  - Use of 3-Dimensional Imaging in Submental Fat Reduction After Deoxycholic Acid
      Injection.

PMID- 29059141
TI  - Use of 3-Dimensional Imaging in Submental Fat Reduction After Cryolipolysis.

PMID- 29059142
TI  - Impact of National Comprehensive Cancer Network Guidelines on Case Selection and
      Outcomes for Sentinel Lymph Node Biopsy in Thin Melanoma.
AB  - BACKGROUND: In 2010, the National Comprehensive Cancer Network (NCCN) recommended
      sentinel lymph node biopsy (SLNB) for thin melanomas <=1 mm with mitotic rate
      (MR) >=1. In 2016, the criteria were changed to Breslow depth >0.75 mm and MR
      >=1. OBJECTIVE: To compare the impact of 2010 and 2016 NCCN guidelines on SLNB
      case selection and thin melanoma outcomes. MATERIALS AND METHODS: Ten-year
      retrospective cohort of primary thin melanomas at an academic hospital was
      retroactively stratified for SLNB eligibility using the 2010 and 2016 NCCN
      guidelines. Nodal recurrence-free survival (NRFS) and disease-free survival (DFS)
      were compared. RESULTS: Eight hundred two patients with 859 tumors and median
      follow-up of 79 months were included. Eleven percent fewer tumors qualified for
      SLNB under 2016 versus 2010 NCCN guidelines (19% vs 8%, p < .001). The 2016
      qualifying cases also had lower 10-year NRFS (70.7% vs 95.2%, p < .001) and DFS
      (64.7% vs 91.4%, p < .001). Among 2016-qualifying cases, those that received SLNB
      had improved NRFS (85.6% vs 35.3%, p = .001) and DFS (80.2% vs 30.5%, p < .001)
      as compared to those that did not receive SLNB. CONCLUSION: The 2016 NCCN
      guidelines reduced the number of thin melanomas qualifying for SLNB and more
      accurately selected cases with higher risks of nodal recurrence and death.

PMID- 29059143
TI  - Polyalkylimide: A Nonstable Filler Over Time.
AB  - BACKGROUND: Polyalkylimide hydrogel is supposed to be a permanent, biocompatible
      implant. However, years after subcutaneous implantation clinical complications
      are seen. OBJECTIVE: To increase the understanding of the changes that occur over
      time in this subdermal implanted filler. MATERIALS AND METHODS: The extruded
      filler material of 34 patients was evaluated by histologic examination. RESULTS:
      In most patients who had cosmetic disturbances but no complaints, histology
      showed no immune cells in or around the filler material. In patients with an
      acute inflammatory response, giant cell invasion was seen in and around the
      filler material. Patients with chronic complaints showed a neutrophilic cell
      influx in the extruded filler. In all patients, degeneration and calcification of
      the material was noted. The polyalkylimide hydrogel changed over time, both
      macroscopically and microscopically. As in most of the patients no immune
      response was seen around the filler material, this may indicate that the material
      is biocompatible. CONCLUSION: The authors conclude that a dermal filler should
      not be judged solely on its biocompatible characteristics but also on the
      degradation process over time in the human body.

PMID- 29059144
TI  - Commentary on ATX-101 (Deoxycholic Acid Injection) for Paradoxical Adipose
      Hyperplasia Secondary to Cryolipolysis.

PMID- 29059145
TI  - Commentary on Improving Sun-Protective Behaviors and Self-Skin Examinations Among
      African Americans.

PMID- 29059146
TI  - Randomized, Evaluator-Blinded Study Comparing Safety and Effect of Two Hyaluronic
      Acid Gels for Lips Enhancement.
AB  - BACKGROUND: Hyaluronic acid (HA) fillers may differ in terms of gel
      characteristics and ease of use and it is of interest whether this might affect
      safety and duration of effect. OBJECTIVE: To compare the long-term safety and
      effect of 2 HA fillers produced by 2 different technologies for lip enhancement.
      MATERIALS AND METHODS: Subjects with very thin to moderately thick lips were
      randomized and treated with HA-RK (N = 31) or HA-JV (N = 29) to improve lip
      fullness by >= 1 grade on a 5-point scale, using a maximum of 3 mL of product.
      RESULTS: A smaller volume of HA-RK compared with HA-JV was required to improve
      lip fullness by >= 1 grade (mean: 1.54 mL vs 1.94 mL, p < .001). Despite the
      smaller volume, lip fullness and global aesthetic improvement were comparably
      sustained in both groups. At 6 months, 60.0% versus 57.7% of subjects (HA-RK vs
      HA-JV) had improved lip fullness. At 12 months, 71.4% versus 76.0% had aesthetic
      improvement (blinded evaluations) and 85.7% versus 86.2% felt more attractive.
      Both products were well tolerated. CONCLUSION: Both products achieved durable
      improvement in lip fullness and aesthetic appearance. A significantly smaller
      amount of HA-RK was required compared with HA-JV to achieve optimal treatment
      effect.

PMID- 29059147
TI  - Atypical Melanocytic Proliferations: A Review of the Literature.
AB  - BACKGROUND: Ambiguous histopathologic diagnoses represent a challenge for
      clinicians because of a lack of definitive diagnosis and related uncertainty
      about management. OBJECTIVE: To review the literature on atypical melanocytic
      proliferations and detail synonymous terms, epidemiology, diagnostic work-up,
      histopathology, treatment, and prognosis. METHODS: Databases from PubMed and Web
      of Science were searched for articles related to atypical melanocytic
      proliferations. RESULTS: Intraepidermal melanocytic proliferations with features
      worrisome for possible melanoma in situ (MIS) are generally excised as for MIS.
      Reported rates of upstaging of such cases to invasive melanoma on review of the
      excision are very low. Because invasion, lymph node spread, and metastasis can
      occur in atypical melanocytic lesions with a thick intradermal component, these
      are often treated as for malignant melanoma. CONCLUSION: Because the diagnosis
      dictates treatment, it is incumbent to establish a diagnosis as definitive as
      possible, obtaining second or third opinions and using ancillary studies when
      appropriate. When the diagnosis remains uncertain, it is difficult to provide
      guidelines for treatment. Clinical care decisions for patients with an uncertain
      diagnosis are best done on a case-by-case basis weighing probabilities of adverse
      outcomes against potential benefits and risks from various treatment options.

PMID- 29059148
TI  - Effect of Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Blockade in
      Rats with Cecal Ligation and Puncture (CLP)-Induced Sepsis.
AB  - BACKGROUND Blocking of TREM-1 signaling improves survival of mice with sepsis
      induced by Pseudomonas aeruginosa. However, whether TREM-1 blockade has
      beneficial effects in polymicrobial sepsis is poorly understood. Here, we aimed
      to investigate the effect of modulation of the TREM-1 pathway in rats with
      polymicrobial sepsis induced by cecal ligation and puncture (CLP). MATERIAL AND
      METHODS Normal Sprague-Dawley (SD) rats with sepsis induced by CLP were allocated
      randomly to received scramble peptide or LP17 via the jugular vein. Serum level
      of sTREM-1, IL6, TNF-alpha, and IL-1beta were detected by ELISA assay. The mRNA
      and protein levels of JAK2 and STAT3 were detected by real-time PCR and Western
      blot analysis. RESULTS STREM-1 concentration was greatly and progressively
      increased in rats with CLP-induced sepsis, and the increase was attenuated by
      TREM-1 inhibitory peptide LP17. More than 60% survival was observed in rats at
      the experiment endpoint after LP17 treatment. TREM-1 blockade also attenuated the
      increased level of pro-inflammatory cytokines TNF-alpha, IL-6, and IL-1beta, and
      thus attenuated systematic and distant inflammatory responses. Furthermore, TREM
      1 blockade significantly attenuated the increased levels of pJAK2 and pSTAT3.
      CONCLUSIONS TREM-1 blockade by the use of an inhibitory peptide LP17 could
      prolong survival of rats with polymicrobial sepsis and attenuate systematic
      inflammatory responses through the JAK2/STAT3 signaling pathway. Our results
      suggest that modulation of TREM-1 by a synthetic peptide might be a potential
      therapeutic option for polymicrobial sepsis.

PMID- 29059150
TI  - Protein phosphatase 1 regulatory subunit 1A in ewing sarcoma tumorigenesis and
      metastasis.
AB  - Protein phosphatase inhibitors are often considered as tumor promoters. Protein
      phosphatase 1 regulatory subunit 1A (PPP1R1A) is a potent protein phosphatase 1
      (PP1) inhibitor; however, its role in tumor development is largely undefined.
      Here we characterize, for the first time, the functions of PPP1R1A in Ewing
      sarcoma (ES) pathogenesis. We found that PPP1R1A is one of the top ranked target
      genes of EWS/FLI, the master regulator of ES, and is upregulated by EWS/FLI via a
      GGAA microsatellite enhancer element. Depletion of PPP1R1A resulted in a
      significant decrease in oncogenic transformation and cell migration in vitro as
      well as xenograft tumor growth and metastasis in an orthotopic mouse model. RNA
      sequencing and functional annotation analyses revealed that PPP1R1A regulates
      genes associated with various cellular functions including cell junction,
      adhesion and neurogenesis. Interestingly, we found a significant overlap of
      PPP1R1A-regulated gene set with that of ZEB2 and EWS, which regulates metastasis
      and neuronal differentiation in ES, respectively. Further studies for
      characterization of the molecular mechanisms revealed that activation of PPP1R1A
      by PKA phosphorylation at Thr35, and subsequent PP1 binding and inhibition, was
      required for PPP1R1A-mediated tumorigenesis and metastasis, likely by increasing
      the phosphorylation levels of various PP1 substrates. Furthermore, we found that
      a PKA inhibitor impaired ES cell proliferation, tumor growth and metastasis,
      which was rescued by the constitutively active PPP1R1A. Together, these results
      offered new insights into the role and mechanism of PPP1R1A in tumor development
      and identified an important kinase and phosphatase pathway, PKA/PPP1R1A/PP1, in
      ES pathogenesis. Our findings strongly suggest a potential therapeutic value of
      inhibition of the PKA/PPP1R1A/PP1 pathway in the treatment of primary and
      metastatic ES.

PMID- 29059149
TI  - Targeting immunosuppressive adenosine in cancer.
AB  - Despite the success of anti-programmed cell death protein 1 (PD1), anti-PD1
      ligand 1 (PDL1) and anti-cytotoxic T lymphocyte antigen 4 (CTLA4) therapies in
      advanced cancer, a considerable proportion of patients remain unresponsive to
      these treatments (known as innate resistance). In addition, one-third of patients
      relapse after initial response (known as adaptive resistance), which suggests
      that multiple non-redundant immunosuppressive mechanisms coexist within the
      tumour microenvironment. A major immunosuppressive mechanism is the adenosinergic
      pathway, which now represents an attractive new therapeutic target for cancer
      therapy. Activation of this pathway occurs within hypoxic tumours, where
      extracellular adenosine exerts local suppression through tumour-intrinsic and
      host-mediated mechanisms. Preclinical studies in mice with adenosine receptor
      antagonists and antibodies have reported favourable antitumour immune responses
      with some definition of the mechanism of action. Currently, agents targeting the
      adenosinergic pathway are undergoing first-in-human clinical trials as single
      agents and in combination with anti-PD1 or anti-PDL1 therapies. In this Review,
      we describe the complex interplay of adenosine and adenosine receptors in the
      development of primary tumours and metastases and discuss the merits of targeting
      one or more components that compose the adenosinergic pathway. We also review the
      early clinical data relating to therapeutic agents inhibiting the adenosinergic
      pathway.

PMID- 29059151
TI  - Neurotensin receptor type 2 protects B-cell chronic lymphocytic leukemia cells
      from apoptosis.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) cells are resistant to apoptosis, and
      consequently accumulate to the detriment of normal B cells and patient immunity.
      Because current therapies fail to eradicate these apoptosis-resistant cells, it
      is essential to identify alternative survival pathways as novel targets for
      anticancer therapies. Overexpression of cell-surface G protein-coupled receptors
      drives cell transformation, and thus plays a critical role in malignancies. In
      this study, we identified neurotensin receptor 2 (NTSR2) as an essential driver
      of apoptosis resistance in B-CLL. NTSR2 was highly expressed in B-CLL cells,
      whereas expression of its natural ligand, neurotensin (NTS), was minimal in both
      B-CLL cells and patient plasma. Surprisingly, NTSR2 remained in a constitutively
      active phosphorylated state, caused not by a mutation-induced gain-of-function
      but rather by an interaction with the oncogenic tyrosine kinase receptor TrkB.
      Functional and biochemical characterization revealed that the NTSR2-TrkB
      interaction acts as a conditional oncogenic driver requiring the TrkB ligand
      brain-derived neurotrophic factor (BDNF), which unlike NTS is highly expressed in
      B-CLL cells. Together, NTSR2, TrkB and BDNF induce autocrine and/or paracrine
      survival pathways that are independent of mutation status and indolent or
      progressive disease course. The NTSR2-TrkB interaction activates survival
      signaling pathways, including the Src and AKT kinase pathways, as well as
      expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL. When NTSR2 was
      downregulated, TrkB failed to protect B-CLL cells from a drastic decrease in
      viability via typical apoptotic cell death, reflected by DNA fragmentation and
      Annexin V presentation. Together, our findings demonstrate that the NTSR2-TrkB
      interaction plays a crucial role in B-CLL cell survival, suggesting that
      inhibition of NTSR2 represents a promising targeted strategy for treating B-CLL
      malignancy.

PMID- 29059152
TI  - MiR-22 sustains NLRP3 expression and attenuates H. pylori-induced gastric
      carcinogenesis.
AB  - Chronic inflammation is the primary cause of gastric cancer (GC). NLRP3, as an
      important inflammasome component, has crucial roles in initiating inflammation.
      However, the potential roles of NLRP3 in GC is unknown. Here, we show that NLRP3
      expression is markedly upregulated in GC, which promotes NLRP3 inflammasome
      activation and interleukin-1beta (IL-1beta) secretion in macrophages. In
      addition, NLRP3 binds to cyclin-D1 (CCND1) promoter and promotes its
      transcription in gastric epithelial cells. Consequently, NLRP3 enhances
      epithelial cells proliferation and GC tumorigenesis. Furthermore, we identify miR
      22, which is constitutively expressed in gastric mucosa, as a suppressor of
      NLRP3. MiR-22 directly targets NLRP3 and attenuates its oncogenic effects in
      vitro and in vivo. However, Helicobacter pylori (H. pylori) infection suppresses
      miR-22 expression, while enhances NLRP3 expression, and that triggers
      uncontrolled proliferation of epithelial cells and the emergence of GC. Thus, our
      research describes a mechanism by which miR-22 suppresses NLRP3 and maintains
      homeostasis of gastric microenvironments and suggests miR-22 as a potential
      target for the intervention of GC.

PMID- 29059153
TI  - Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1
      regulation.
AB  - Elevated O-GlcNAcylation is associated with disease states such as diabetes and
      cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition
      of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we
      show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT
      regulates expression of the master lipid regulator the transcription factor
      sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional
      targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein
      expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT
      mediated regulation of cell survival and of lipid synthesis, as overexpression of
      SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor
      growth in vitro and in vivo. These results unravel a previously unidentified link
      between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer
      and suggests a crucial role for O-GlcNAc signaling in transducing nutritional
      state to regulate lipid metabolism.

PMID- 29059154
TI  - Fibroblast growth factor 13 regulates glioma cell invasion and is important for
      bevacizumab-induced glioma invasion.
AB  - Glioblastoma has the poorest prognosis, and is characterized by excessive
      invasion and angiogenesis. To determine the invasive mechanisms, we previously
      used two glioma cell lines (J3T-1 and J3T-2) with different invasive phenotypes.
      The J3T-1 showed abundant angiogenesis and tumor cell invasion around
      neovasculature, while J3T-2 showed diffuse cell infiltration into surrounding
      healthy parenchyma. Microarray analyses were used to identify invasion-related
      genes in J3T-2 cells, and the expressed genes and their intracellular and
      intratumoral distribution patterns were evaluated in J3T-2 cell lines, human
      glioma cell lines, human glioblastoma stem cells and human glioblastoma
      specimens. To determine the role of the invasion-related genes, invasive
      activities were evaluated in vitro and in vivo. Fibroblast growth factor 13
      (FGF13) was overexpressed in J3T-2 cells compared to J3T-1 cells, and in human
      glioma cell lines, human glioblastoma stem cells and human glioblastoma
      specimens, when compared to that of normal human astrocytes. Immunohistochemical
      staining and the RNA-seq (sequencing) data from the IVY Glioblastoma Atlas
      Project showed FGF13 expression in glioma cells in the invasive edges of tumor
      specimens. Also, the intracellular distribution was mainly in the cytoplasm of
      tumor cells and colocalized with tubulin. Overexpression of FGF13 stabilized
      tubulin dynamics in vitro and knockdown of FGF13 decreased glioma invasion both
      in vitro and in vivo and prolonged overall survival of several xenograft models.
      FGF13 was negatively regulated by hypoxic condition. Silencing of FGF13 also
      decreased in vivo bevacizumab-induced glioma invasion. In conclusion, FGF13
      regulated glioma cell invasion and bevacizumab-induced glioma invasion, and could
      be a novel target for glioma treatment.

PMID- 29059155
TI  - Reactivation of androgen receptor-regulated lipid biosynthesis drives the
      progression of castration-resistant prostate cancer.
AB  - Androgen receptor (AR) is a transcriptional activator that, in prostate cells,
      stimulates gene expression required for various cellular functions, including
      metabolisms and proliferation. AR signaling is also essential for the development
      of hormone-dependent prostate cancer (PCa) and its activity can be blocked by
      androgen-deprivation therapies (ADTs). Although PCa patients initially respond
      well to ADTs, the cancer inevitably relapses and progresses to lethal castration
      resistant prostate cancer (CRPC). Although AR activity is generally restored in
      CRPC despite the castrate level of androgens, it is unclear whether AR signaling
      is significantly reprogrammed. In this study, we examined the AR cistrome in a
      PCa cell line-derived CRPC model using integrated bioinformatical analyses.
      Significantly, we found that the AR cistrome is largely retained in the CRPC
      stage. In particular, AR-mediated lipid biosynthesis is highly conserved and
      reactivated during the progression to CRPC, and increased level of lipid
      synthesis is associated with poor prognosis. The restoration of lipid
      biosynthetic pathways is partially due to the increased expression of AR splice
      variants. Blocking lipid/cholesterol synthesis in AR variants-expressing CRPC
      cell line and xenograft models markedly reduces tumor growth through inhibition
      of mTOR pathway. Silencing the expression of a fatty acid elongase, ELOVL7, also
      leads to the regression of CRPC xenograft tumors. These results demonstrate the
      importance of reactivation of AR-regulated lipid biosynthetic pathways in driving
      CRPC progression, and suggest that ADTs may be therapeutically enhanced by
      blocking lipid biosynthetic pathways.

PMID- 29059156
TI  - Extracellular matrix protein 1 promotes cell metastasis and glucose metabolism by
      inducing integrin beta4/FAK/SOX2/HIF-1alpha signaling pathway in gastric cancer.
AB  - Extracellular matrix protein 1 (ECM1) is related to strong invasiveness and poor
      prognosis in major malignancies, but the underlying mechanism remains unknown.
      Here we aimed to elucidate the function of ECM1 on cell metastasis and glucose
      metabolism in gastric cancer (GC). The level of ECM1 in sera and tissues of
      patient with GC were positively correlated with tumor invasion and recurrence.
      Genetic manipulation of ECM1 expression affected cell metastasis and glucose
      metabolism in GC cell lines. Enhanced ECM1 expression facilitated gene expression
      levels associated with epithelial-mesenchymal transition (EMT) and glucose
      metabolism. Interestingly, our results indicated that ECM1 directly interacted
      with integrin beta4 (ITGB4) and activated ITGB4/focal adhesion kinase
      (FAK)/glycogen synthase kinase 3beta signaling pathway, which further induced the
      expression of transcription factor SOX2. Aberrant expression of SOX2 altered gene
      expression of EMT factors and glucose metabolism enzymes. Furthermore, SOX2
      enhanced hypoxia-inducible factor alpha (HIF-1alpha) promoter activity to
      regulate glucose metabolism. The micro-positron emission tomography/computed
      tomography imaging of xenograft model showed that ECM1 substantially increased
      18F-fluorodeoxyglucose uptake in xenograft tumors. Using in vivo mouse tail vein
      injection experiments, ECM1 was also found to increase in lung surface
      metastasis. These findings provide evidence that ECM1 regulates GC cell
      metastasis and glucose metabolism by inducing ITGB4/FAK/SOX2/HIF-1alpha signal
      pathway and have important implications for the development of therapeutic target
      to prevent tumor metastasis and recurrence.

PMID- 29059157
TI  - EphrinB1 promotes cancer cell migration and invasion through the interaction with
      RhoGDI1.
AB  - Eph receptors and their corresponding ephrin ligands have been associated with
      regulating cell-cell adhesion and motility, and thus have a critical role in
      various biological processes including tissue morphogenesis and homeostasis, as
      well as pathogenesis of several diseases. Aberrant regulation of Eph/ephrin
      signaling pathways is implicated in tumor progression of various human cancers.
      Here, we show that a Rho family GTPase regulator, Rho guanine nucleotide
      dissociation inhibitor 1 (RhoGDI1), can interact with ephrinB1, and this
      interaction is enhanced upon binding the extracellular domain of the cognate
      EphB2 receptor. Deletion mutagenesis revealed that amino acids 327-334 of the
      ephrinB1 intracellular domain are critical for the interaction with RhoGDI1.
      Stimulation with an EphB2 extracellular domain-Fc fusion protein (EphB2-Fc)
      induces RhoA activation and enhances the motility as well as invasiveness of wild
      type ephrinB1-expressing cells. These Eph-Fc-induced effects were markedly
      diminished in cells expressing the mutant ephrinB1 construct (Delta327-334) that
      is ineffective at interacting with RhoGDI1. Furthermore, ephrinB1 depletion by
      siRNA suppresses EphB2-Fc-induced RhoA activation, and reduces motility and
      invasiveness of the SW480 and Hs578T human cancer cell lines. Our study connects
      the interaction between RhoGDI1 and ephrinB1 to the promotion of cancer cell
      behavior associated with tumor progression. This interaction may represent a
      therapeutic target in cancers that express ephrinB1.

PMID- 29059158
TI  - RAF inhibitor LY3009120 sensitizes RAS or BRAF mutant cancer to CDK4/6 inhibition
      by abemaciclib via superior inhibition of phospho-RB and suppression of cyclin
      D1.
AB  - KRAS, NRAS and BRAF mutations are among the most important oncogenic drivers in
      many major cancer types, such as melanoma, lung, colorectal and pancreatic
      cancer. There is currently no effective therapy for the treatment of RAS mutant
      cancers. LY3009120, a pan-RAF and RAF dimer inhibitor advanced to clinical study
      has been shown to inhibit both RAS and BRAF mutant cell proliferation in vitro
      and xenograft tumor growth in vivo. Abemaciclib, a CDK4/6-selective inhibitor, is
      currently in phase III studies for ER-positive breast cancer and KRAS mutant lung
      cancer. In this study, we found that combinatory treatment with LY3009120 and
      abemaciclib synergistically inhibited proliferation of tumor cells in vitro and
      led to tumor growth regression in xenograft models with a KRAS, NRAS or BRAF
      mutation at the doses of two drugs that were well tolerated in combination.
      Further in vitro screen in 328 tumor cell lines revealed that tumor cells with
      KRAS, NRAS or BRAF mutation, or cyclin D activation are more sensitive, whereas
      tumor cells with PTEN, PIK3CA, PIK3R1 or retinoblastoma (Rb) mutation are more
      resistant to this combination treatment. Molecular analysis revealed that
      abemaciclib alone inhibited Rb phosphorylation partially and caused an increase
      of cyclin D1. The combinatory treatment cooperatively demonstrated more complete
      inhibition of Rb phosphorylation, and LY3009120 suppressed the cyclin D1
      upregulation mediated by abemaciclib. These results were further verified by
      CDK4/6 siRNA knockdown. Importantly, the more complete phospho-Rb inhibition and
      cyclin D1 suppression by LY3009120 and abemaciclib combination led to more
      significant cell cycle G0/G1 arrest of tumor cells. These preclinical findings
      suggest that combined inhibition of RAF and d-cyclin-dependent kinases might
      provide an effective approach to treat patients with tumors harboring mutations
      in RAS or RAF genes.

PMID- 29059159
TI  - Wild-type KRAS is a novel therapeutic target for melanoma contributing to primary
      and acquired resistance to BRAF inhibition.
AB  - Malignant melanoma reveals rapidly increasing incidence and mortality rates
      worldwide. By now, BRAF inhibition is the standard therapy for advanced melanoma
      in patients carrying BRAF mutations. However, only approximately 50% of melanoma
      patients harbor therapeutically attackable BRAF mutations, and overall survival
      after treatment with BRAF inhibitors is modest. KRAS (Kirsten Rat sarcoma)
      proteins are acting upstream of BRAF and have a major role in human cancer.
      Recent approaches awaken the hope to use KRAS inhibition (KRASi) as a clinical
      tool. In this study, we identified wild-type KRAS as a novel therapeutic target
      in melanoma. KRASi functions synergistically with BRAF inhibition to reduce
      melanoma proliferation and to induce apoptosis independently of BRAF mutational
      status. Moreover, acquired resistance to BRAF inhibitors in melanoma is dependent
      on dynamic regulation of KRAS expression with subsequent AKT and extracellular
      signal regulated kinase activation and can be overcome by KRASi. This suggests
      KRASi as novel approach in melanoma-alone or in combination with other
      therapeutic regimes.

PMID- 29059160
TI  - IL6 derived from cancer-associated fibroblasts promotes chemoresistance via CXCR7
      in esophageal squamous cell carcinoma.
AB  - Various factors and cellular components in the tumor microenvironment are key
      drivers associated with drug resistance in many cancers. Here, we analyzed the
      factors and molecular mechanisms involved in chemoresistance in patients with
      esophageal squamous cell carcinoma (ESCC). We found that interleukin 6 (IL6)
      derived mainly from cancer-associated fibroblasts played the most important role
      in chemoresistance by upregulating C-X-C motif chemokine receptor 7 (CXCR7)
      expression through signal transducer and activator of transcription 3/nuclear
      factor-kappaB pathway. CXCR7 knockdown resulted in the inhibition of IL6-induced
      proliferation and chemoresistance. In addition, CXCR7 silencing significantly
      decreased gene expression associated with stemness, chemoresistance and
      epithelial-mesenchymal transition and suppressed the proliferation ability of
      ESCC cells in three-dimensional culture systems and angiogenesis assay. In
      clinical samples, ESCC patients with high expression of CXCR7 and IL6 presented a
      significantly worse overall survival and progression-free survival upon receiving
      cisplatin after operation. These results suggest that the IL6-CXCR7 axis may
      provide a promising target for the treatment of ESCC.

PMID- 29059161
TI  - Plk1 phosphorylation of Numb leads to impaired DNA damage response.
AB  - Although Numb is well-recognized as a cell-fate determinant in stem/progenitor
      cells, accumulating evidence supports that Numb also has a critical role in adult
      tissues and cancers, in particular, in the context of regulation of tumor
      suppressor p53. Herein, we identified Numb as a novel substrate of Polo-like
      kinase 1 (Plk1). Of significance, we showed that Plk1-mediated phosphorylation of
      Numb leads to its enhanced proteasomal degradation and impaired Numb/p53 pathway,
      thus providing another mechanism how Plk1 antagonizes p53 during DNA damage
      response. In addition, the novel phosphorylation event identified by us further
      supports the notion that post-translational modifications of Numb uncouple Numb
      from p53 and lead to p53 destabilization. Finally, our data generated from both
      human cancer cell lines and mouse xenograft model showed that cancer cells
      carrying the unphosphorylated form of Numb by Plk1 are more sensitive to
      doxorubicin, a classical chemotherapeutic drug. Therefore, our work may provide
      future strategies for improving the efficacy of chemotherapy by targeting Numb
      phosphorylation by Plk1.

PMID- 29059162
TI  - Activation of PPARalpha by clofibrate sensitizes pancreatic cancer cells to
      radiation through the Wnt/beta-catenin pathway.
AB  - Radiotherapy is emerging as an important modality for the local control of
      pancreatic cancer, but pancreatic cancer cell radioresistance remains a serious
      concern. Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member
      of the PPAR nuclear hormone receptor superfamily, which can be activated by
      fibrate ligands. The clinical relevance of PPARalpha and its biological function
      in pancreatic cancer radiosensitivity have not been previously described. In this
      study, we examined PPARalpha expression in tissue samples of pancreatic cancer
      patients. We found significantly higher expression of PPARalpha in pancreatic
      cancer tissues than in tumor-adjacent tissues and that the PPARalpha expression
      level is inversely associated with higher overall patient survival rate. We
      further observed that PPARalpha activation by its agonist clofibrate sensitizes
      pancreatic cancer cells to radiation by modulating cell cycle progression and
      apoptosis in several pancreatic cancer cell lines. Small interfering RNA-mediated
      PPARalpha silencing and PPARalpha blockade by the antagonist GW6471 abolish the
      effect of clofibrate on radiosensitization. An in vivo study showed that PANC1
      xenografts treated with clofibrate are more sensitive to radiation than untreated
      xenografts. mRNA profiling by microarray analysis revealed that the expression of
      PTPRZ1 and Wnt8a, two core components of the beta-catenin pathway, is
      downregulated by clofibrate. Chromatin immunoprecipitation analysis confirmed
      that clofibrate abrogates the binding of nuclear factor-kappaB to the PTPRZ1 and
      Wnt8a promoters, ultimately decreasing Wnt/beta-catenin signaling activity, which
      is associated with radiosensitivity. Overall, we demonstrate that PPARalpha is
      overexpressed in pancreatic cancer tissues and clofibrate-mediated PPARalpha
      activation sensitizes pancreatic cancer cells to radiation through the Wnt/beta
      catenin pathway.

PMID- 29059163
TI  - Molecular genetics and cellular events of K-Ras-driven tumorigenesis.
AB  - Cellular transformation and the accumulation of genomic instability are the two
      key events required for tumorigenesis. K-Ras (Kirsten-rat sarcoma viral oncogene
      homolog) is a prominent oncogene that has been proven to drive tumorigenesis. K
      Ras also modulates numerous genetic regulatory mechanisms and forms a large
      tumorigenesis network. In this review, we track the genetic aspects of K-Ras
      signaling networks and assemble the sequence of cellular events that constitute
      the tumorigenesis process, such as regulation of K-Ras expression (which is
      influenced by miRNA, small nucleolar RNA and lncRNA), activation of K-Ras
      (mutations), generation of reactive oxygen species (ROS), induction of DNA damage
      and apoptosis, induction of DNA damage repair pathways and ROS detoxification
      systems, cellular transformation after apoptosis by the blebbishield emergency
      program and the accumulation of genomic/chromosomal instability that leads to
      tumorigenesis.

PMID- 29059165
TI  - Thirty years of Oncogene.

PMID- 29059164
TI  - FAM49B, a novel regulator of mitochondrial function and integrity that suppresses
      tumor metastasis.
AB  - Mitochondrial dysregulation plays a central role in cancers and drives reactive
      oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral
      roles of mitochondrial dynamics and altered intracellular ROS levels in
      pancreatic ductal adenocarcinoma (PDAC). We identified 'family with sequence
      similarity 49 member B' (FAM49B) as a mitochondria-localized protein that
      regulates mitochondrial fission and cancer progression. Silencing FAM49B in PDAC
      cells resulted in increased fission and mitochondrial ROS generation, which
      enhanced PDAC cell proliferation and invasion. Notably, FAM49B expression levels
      in PDAC cells were downregulated by the tumor microenvironment. Overall, the
      results of this study show that FAM49B acts as a suppressor of cancer cell
      proliferation and invasion in PDAC by regulating tumor mitochondrial redox
      reactions and metabolism.

PMID- 29059166
TI  - mTORC2/AKT/HSF1/HuR constitute a feed-forward loop regulating Rictor expression
      and tumor growth in glioblastoma.
AB  - Overexpression of Rictor has been demonstrated to result in increased mechanistic
      target of rapamycin C2 (mTORC2) nucleation and activity leading to tumor growth
      and increased invasive characteristics in glioblastoma multiforme (GBM). However,
      the mechanisms regulating Rictor expression in these tumors is not clearly
      understood. In this report, we demonstrate that Rictor is regulated at the level
      of mRNA translation via heat-shock transcription factor 1 (HSF1)-induced HuR
      activity. HuR is shown to directly bind the 3' untranslated region of the Rictor
      transcript and enhance translational efficiency. Moreover, we demonstrate that
      mTORC2/AKT signaling activates HSF1 resulting in a feed-forward cascade in which
      continued mTORC2 activity is able to drive Rictor expression. RNAi-mediated
      blockade of AKT, HSF1 or HuR is sufficient to downregulate Rictor and inhibit GBM
      growth and invasive characteristics in vitro and suppress xenograft growth in
      mice. Modulation of AKT or HSF1 activity via the ectopic expression of mutant
      alleles support the ability of AKT to activate HSF1 and demonstrate continued
      HSF1/HuR/Rictor signaling in the context of AKT knockdown. We further show that
      constitutive overexpression of HuR is able to maintain Rictor expression under
      conditions of AKT or HSF1 loss. The expression of these components is also
      examined in patient GBM samples and correlative associations between the relative
      expression of these factors support the presence of these signaling relationships
      in GBM. These data support a role for a feed-forward loop mechanism by which
      mTORC2 activity stimulates Rictor translational efficiency via an AKT/HSF1/HuR
      signaling cascade resulting in enhanced mTORC2 activity in these tumors.

PMID- 29059167
TI  - Loss of RhoA promotes skin tumor formation and invasion by upregulation of RhoB.
AB  - Cellular movement is controlled by small GTPases, such as RhoA. Although
      migration is crucial for cancer cell invasion, the specific role of RhoA in tumor
      formation is unclear. Inducing skin tumors in mice with a keratinocyte-restricted
      loss of RhoA, we observed increased tumor frequency, growth and invasion. In
      vitro invasion assays revealed that in the absence of RhoA cell invasiveness is
      increased in a Rho-associated protein kinase (ROCK) activation and cell
      contraction-dependent manner. Surprisingly, loss of RhoA causes increased Rho
      signaling via overcompensation by RhoB because of reduced lysosomal degradation
      of RhoB in Gamma-aminobutyric acid receptor-associated protein (GABARAP)+
      autophagosomes and endosomes. In the absence of RhoA, RhoB relocalized to the
      plasma membrane and functionally replaced RhoA with respect to invasion,
      clonogenic growth and survival. Our data demonstrate for the first time that RhoA
      is a tumor suppressor in 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol
      13-acetate skin carcinogenesis and identify Rho signaling dependent on RhoA and
      RhoB as a potent driver of tumor progression.

PMID- 29059168
TI  - Oncogenic FLT3-ITD supports autophagy via ATF4 in acute myeloid leukemia.
AB  - In acute myeloid leukemia (AML), internal tandem duplication mutations in the
      FLT3 tyrosine kinase receptor (FLT3-ITD) account for up to 25% of cases and are
      associated with a poor outcome. In order to better target this AML subtype, a
      comprehensive view of how FLT3-ITD impacts AML cell biology is required. Here, we
      found that FLT3-ITD expression increased basal autophagy in AML cells, and that
      both pharmacological and genetic inhibition of the receptor reduced autophagy in
      primary AML samples and cell lines. Conditional expression of shRNAs against key
      autophagy proteins demonstrated that autophagy is required for AML cell
      proliferation in vitro and for leukemic cells survival in a mouse model of
      xenograft. Importantly, autophagy inhibition also overcame FLT3 inhibitor
      resistance both in vitro and in vivo. The transcription factor ATF4 was
      identified as an essential actor of FLT3-ITD-induced autophagy. Cellular levels
      of ATF4 were highly dependent on FLT3-ITD activity, and downregulation of ATF4
      inhibited autophagy-dependent AML cell proliferation and improved overall mouse
      survival similarly to autophagy inhibition. These results suggest that targeting
      autophagy or ATF4 in patients expressing FLT3 mutations may represent a novel
      promising and innovative therapeutic strategy for AML.

PMID- 29059169
TI  - Metformin regulates global DNA methylation via mitochondrial one-carbon
      metabolism.
AB  - The anti-diabetic biguanide metformin may exert health-promoting effects via
      metabolic regulation of the epigenome. Here we show that metformin promotes
      global DNA methylation in non-cancerous, cancer-prone and metastatic cancer cells
      by decreasing S-adenosylhomocysteine (SAH), a strong feedback inhibitor of S
      adenosylmethionine (SAM)-dependent DNA methyltransferases, while promoting the
      accumulation of SAM, the universal methyl donor for cellular methylation. Using
      metformin and a mitochondria/complex I (mCI)-targeted analog of metformin
      (norMitoMet) in experimental pairs of wild-type and AMP-activated protein kinase
      (AMPK)-, serine hydroxymethyltransferase 2 (SHMT2)- and mCI-null cells, we
      provide evidence that metformin increases the SAM:SAH ratio-related methylation
      capacity by targeting the coupling between serine mitochondrial one-carbon flux
      and CI activity. By increasing the contribution of one-carbon units to the SAM
      from folate stores while decreasing SAH in response to AMPK-sensed energetic
      crisis, metformin can operate as a metabolo-epigenetic regulator capable of
      reprogramming one of the key conduits linking cellular metabolism to the DNA
      methylation machinery.

PMID- 29059170
TI  - SPSB3 targets SNAIL for degradation in GSK-3beta phosphorylation-dependent manner
      and regulates metastasis.
AB  - Epithelial-mesenchymal transition (EMT) is a process during which normal
      epithelial cells acquire mesenchymal characteristics. EMT has a critical role in
      various human diseases especially in cancer. EMT facilitates tumor initiation and
      progression by mediating cancer cell stemness and motility. Zinc finger
      transcription factor SNAIL is one of the most important initiators of EMT.
      Therefore, it is of great significance to understand the regulating mechanism of
      SNAIL. In this study, we carried out a luciferase-based genome-wide screening
      using small interfering RNA library against ~200 of E3 ligases and ubiquitin
      related genes and identified SOCS box protein SPSB3 as a novel E3 ligase
      component that targets SNAIL into polyubiquitination and degradation in response
      to GSK-3beta phosphorylation of SNAIL. Functionally, we observed that SPSB3
      overexpression greatly inhibits tumor metastasis by regulating SNAIL degradation
      both in vitro and in vivo. The expression of SPSB3 and SNAIL are negatively
      correlated in human esophageal squamous cell carcinoma tissues, and low SPSB3
      expression indicates lymph node metastasis. Moreover, high SPSB3 expression
      indicates good survivals in various kinds of cancer. Collectively, these findings
      suggest that SPSB3-mediated SNAIL degradation has a vital role in regulating EMT
      and cancer progression.

PMID- 29059171
TI  - Suppression of RAC1-driven malignant melanoma by group A PAK inhibitors.
AB  - Activating mutations in the RAC1 gene have recently been discovered as driver
      events in malignant melanoma. Expression of this gene is associated with
      melanocyte proliferation, and melanoma cells bearing this mutation are
      insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may
      evade immune surveillance due to enhanced expression of PD-L1. Activating
      mutations in RAC1 are of special interest, as small-molecule inhibitors for the
      RAC effector p21-activated kinase (PAK) are in late-stage clinical development
      and might impede oncogenic signaling from mutant RAC1. In this work, we explore
      the effects of PAK inhibition on RAC1P29S signaling in zebrafish embryonic
      development, in the proliferation, survival and motility of RAC1P29S-mutant human
      melanoma cells, and on tumor formation and progression from such cells in mice.
      We report that RAC1P29S evokes a Rasopathy-like phenotype on zebrafish
      development that can be blocked by inhibitors of PAK or MEK. We also found and
      that RAC1-mutant human melanoma cells are resistant to clinical inhibitors of
      BRAF but are uniquely sensitive to PAK inhibitors. These data suggest that
      suppressing the PAK pathway might be of therapeutic benefit in this type of
      melanoma.

PMID- 29059172
TI  - Neuropilin-1 contributes to esophageal squamous cancer progression via promoting
      P65-dependent cell proliferation.
AB  - Neuropilin-1 (NRP1) is a non-kinase receptor recently implicated in tumor
      progression. Here we revealed that over-expression of NRP1 correlates with poor
      prognosis in esophageal squamous cell carcinoma (ESCC). NRP1-knockdown suppressed
      ESCC cell proliferation and xenograft tumor growth. Reduced NRP1 expression
      downregulated P65 mRNA and protein expression, and ectopic expression of P65
      restored cell proliferation in NRP1-silenced cells. NRP1 regulates P65
      transcription by activating cAMP responsive element binding protein (CREB). NRP1
      interacted with and activated epidermal growth factor receptor (EGFR), and b1/b2
      domain of NRP1 is responsible for the activation of EGFR. We also found that EGFR
      regulated CREB transcriptional activity via AKT. These data suggest that NRP1 is
      an upstream regulator in the P65-dependent proliferation signaling pathway and a
      candidate therapeutic target for ESCC.

PMID- 29059173
TI  - SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in
      pancreatic cancer.
AB  - SRY (sex determining region Y)-box 9 (SOX9) is required for oncogenic Kras
      mediated acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasias
      (PanINs) and ultimately pancreatic ductal adenocarcinoma (PDAC). However, how
      oncogenic Kras affects SOX9 activity is not yet understood, and SOX9-associated
      genes in PDAC are also unknown at all. Here, we investigated the mechanistic link
      between SOX9 and oncogenic Kras, studied biological function of SOX9, and
      identified SOX9-related genes and their clinical significance in patients with
      PDAC. Our studies reveal that oncogenic Kras induces SOX9 mRNA and protein
      expression as well as phosphorylated SOX9 expression in human pancreatic ductal
      progenitor cells (HPNE) and pancreatic ductal cells (HPDE). Moreover, oncogenic
      Kras promoted nuclear translocation and transcriptional activity of SOX9 in these
      cells. TAK1/IkappaBalpha/NF-kappaB pathway contributed to induction of SOX9 by
      oncogenic Kras, and SOX9 in turn enhanced NF-kappaB activation. SOX9 promoted the
      proliferation of HPNE and PDAC cells, and correlated with minichromosome
      maintenance complex components (MCMs) and mediator of DNA damage checkpoint 1
      (MDC1) expression. The overexpressive MDC1 was associated with less perineural
      and lymph node invasion of tumors and early TNM-stage of patients. Our results
      indicate that oncogenic Kras induces constitutive activation of SOX9 in HPNE and
      HPDE cells, and Kras/TAK1/IkappaBalpha/NF-kappaB pathway and a positive feedback
      between SOX9 and NF-kappaB are involved in this inducing process. SOX9
      accelerates proliferation of cells and affects MCMs and MDC1 expression. MDC1 is
      associated negatively with invasion and metastasis of PDAC.

PMID- 29059174
TI  - Kinesin superfamily: roles in breast cancer, patient prognosis and therapeutics.
AB  - Breast cancer pathobiology is known to be influenced by the differential
      expression of a group of proteins called the kinesin superfamily (KIFs), which is
      instrumental in the intracellular transport of chromosomes along microtubules
      during mitosis. During cellular division, kinesins are strictly regulated through
      temporal synthesis so that they are present only when needed. However, their
      misregulation may contribute to uncontrolled cell growth owing to premature
      sister chromatid separation, highlighting their importance in cancer. This review
      covers the functions of kinesins in normal and breast cancer cells, the use of
      kinesins for breast cancer patient prognosis, and the targeting of these
      molecules for therapeutics. A better understanding of KIF proteins may be pivotal
      to improved disease outcomes for breast cancer patients.

PMID- 29059175
TI  - Induction of anti-VEGF therapy resistance by upregulated expression of
      microseminoprotein (MSMP).
AB  - Anti-vascular endothelial growth factor (VEGF) therapy has demonstrated efficacy
      in treating human metastatic cancers, but therapeutic resistance is a practical
      limitation and most tumors eventually become unresponsive. To identify
      microenvironmental factors underlying the resistance of cancer to
      antiangiogenesis therapy, we conducted genomic analyses of intraperitoneal
      ovarian tumors in which adaptive resistance to anti-VEGF therapy (B20 antibody)
      developed. We found that expression of the microseminoprotein, prostate
      associated (MSMP) gene was substantially upregulated in resistant compared with
      control tumors. MSMP secretion from cancer cells was induced by hypoxia,
      triggering MAPK signaling in endothelial cells to promote tube formation in
      vitro. Recruitment of the transcriptional repressor CCCTC-binding factor (CTCF)
      to the MSMP enhancer region was decreased by histone acetylation under hypoxic
      conditions in cancer cells. MSMP siRNA, delivered in vivo using the DOPC
      nanoliposomes, restored tumor sensitivity to anti-VEGF therapy. In ovarian cancer
      patients treated with bevacizumab, serum MSMP concentration increased
      significantly only in non-responders. These findings imply that MSMP inhibition
      combined with the use of antiangiogenesis drugs may be a new strategy to overcome
      resistance to antiangiogenesis therapy.

PMID- 29059176
TI  - Candidate genes-based investigation of susceptibility to Human African
      Trypanosomiasis in Cote d'Ivoire.
AB  - Human African Trypanosomiasis (HAT) or sleeping sickness is a Neglected Tropical
      Disease. Long regarded as an invariably fatal disease, there is increasing
      evidence that infection by T. b. gambiense can result in a wide range of clinical
      outcomes, including latent infections, which are long lasting infections with no
      parasites detectable by microscopy. The determinants of this clinical diversity
      are not well understood but could be due in part to parasite or host genetic
      diversity in multiple genes, or their interactions. A candidate gene association
      study was conducted in Cote d'Ivoire using a case-control design which included a
      total of 233 subjects (100 active HAT cases, 100 controls and 33 latent
      infections). All three possible pairwise comparisons between the three phenotypes
      were tested using 96 SNPs in16 candidate genes (IL1, IL4, IL4R, IL6, IL8, IL10,
      IL12, IL12R, TNFA, INFG, MIF, APOL1, HPR, CFH, HLA-A and HLA-G). Data from 77
      SNPs passed quality control. There were suggestive associations at three loci in
      IL6 and TNFA in the comparison between active cases and controls, one SNP in each
      of APOL1, MIF and IL6 in the comparison between latent infections and active
      cases and seven SNP in IL4, HLA-G and TNFA between latent infections and
      controls. No associations remained significant after Bonferroni correction, but
      the Benjamini Hochberg false discovery rate test indicated that there were strong
      probabilities that at least some of the associations were genuine. The excess of
      associations with latent infections despite the small number of samples available
      suggests that these subjects form a distinct genetic cluster different from
      active HAT cases and controls, although no clustering by phenotype was observed
      by principle component analysis. This underlines the complexity of the
      interactions existing between host genetic polymorphisms and parasite diversity.

PMID- 29059177
TI  - Automated deconvolution of structured mixtures from heterogeneous tumor genomic
      data.
AB  - With increasing appreciation for the extent and importance of intratumor
      heterogeneity, much attention in cancer research has focused on profiling
      heterogeneity on a single patient level. Although true single-cell genomic
      technologies are rapidly improving, they remain too noisy and costly at present
      for population-level studies. Bulk sequencing remains the standard for population
      scale tumor genomics, creating a need for computational tools to separate
      contributions of multiple tumor clones and assorted stromal and infiltrating cell
      populations to pooled genomic data. All such methods are limited to coarse
      approximations of only a few cell subpopulations, however. In prior work, we
      demonstrated the feasibility of improving cell type deconvolution by taking
      advantage of substructure in genomic mixtures via a strategy called simplicial
      complex unmixing. We improve on past work by introducing enhancements to automate
      learning of substructured genomic mixtures, with specific emphasis on genome-wide
      copy number variation (CNV) data, as well as the ability to process quantitative
      RNA expression data, and heterogeneous combinations of RNA and CNV data. We
      introduce methods for dimensionality estimation to better decompose mixture model
      substructure; fuzzy clustering to better identify substructure in sparse, noisy
      data; and automated model inference methods for other key model parameters. We
      further demonstrate their effectiveness in identifying mixture substructure in
      true breast cancer CNV data from the Cancer Genome Atlas (TCGA). Source code is
      available at https://github.com/tedroman/WSCUnmix.

PMID- 29059178
TI  - Associations of aerobic and strength exercise with clinical laboratory test
      values.
AB  - OBJECTIVES: Physical exercise may affect levels of blood-based biomarkers.
      However, exercise status is seldom considered in the interpretation of laboratory
      results. This study reports the associations between habitual exercise
      participation and clinical laboratory test results. METHODS: The effects of days
      per week of aerobic and strength exercise participation on laboratory test
      results for 26 biomarkers in young adults aged 18 to 34 years (n = 80,111) were
      evaluated using percentile distribution analyses and multivariate regression.
      RESULTS: In both men and women, more days per week of either aerobic or strength
      exercise were significantly associated with lower levels of glucose, hemoglobin
      A1c, LDL cholesterol, total cholesterol, triglycerides, estimated glomerular
      filtration rate, globulin, and C-reactive protein, and significantly higher
      levels of HDL cholesterol, creatinine, iron, and percent saturation (all p <
      .05). Type of exercise or gender influenced the observed relationships with
      exercise frequency for total cholesterol, aspartate aminotransferase, gamma
      glutamyl transferase, alkaline phosphatase, uric acid, bilirubin, and iron
      binding capacity. CONCLUSIONS: Physical exercise shifted the distribution of
      results into the direction suggestive of better health. Reported relationships
      may help clinicians and patients to better understand and interpret laboratory
      results in athletic populations and possibly re-evaluate interpretation of
      reference intervals for physically active populations.

PMID- 29059179
TI  - Cost-effectiveness of adding indoor residual spraying to case management in
      Afghan refugee settlements in Northwest Pakistan during a prolonged malaria
      epidemic.
AB  - INTRODUCTION: Financing of malaria control for displaced populations is limited
      in scope and duration, making cost-effectiveness analyses relevant but difficult.
      This study analyses cost-effectiveness of adding prevention through targeted
      indoor residual spraying (IRS) to case management in Afghan refugee settlements
      in Pakistan during a prolonged malaria epidemic. METHODS/FINDINGS: An
      intervention study design was selected, taking a societal perspective. Provider
      and household costs of vector control and case management were collected from
      provider records and community survey. Health outcomes (e.g. cases and DALYs
      averted) were derived and incremental cost-effectiveness ratios (ICERs) for cases
      prevented and DALYs averted calculated. Population, treatment cost, women's time,
      days of productivity lost, case fatality rate, cases prevented, and DALY
      assumptions were tested in sensitivity analysis. Malaria incidence peaked at
      44/1,000 population in year 2, declining to 14/1,000 in year 5. In total, 370,000
      malaria cases, 80% vivax, were diagnosed and treated and an estimated 67,988
      vivax cases and 18,578 falciparum and mixed cases prevented. Mean annual
      programme cost per capita was US$0.56. The additional cost of including IRS over
      five years per case prevented was US$39; US$50 for vivax (US$43 in years 1-3,
      US$80 in years 4-5) and US$182 for falciparum (US$139 in years 1-3 and US$680 in
      years 4-5). Per DALY averted this was US$266 (US$220 in years 1-3 and US$486 in
      years 4-5) and thus 'highly cost-effective' or cost-effective using WHO and
      comparison thresholds. CONCLUSIONS: Adding IRS was cost-effective in this
      moderate endemicity, low mortality setting. It was more cost-effective when
      transmission was highest, becoming less so as transmission reduced. Because vivax
      was three times more common than falciparum and the case fatality rate was low,
      cost-effectiveness estimations for cases prevented appear reliable and more
      definitive for vivax malaria.

PMID- 29059180
TI  - Diverse type 2 diabetes genetic risk factors functionally converge in a phenotype
      focused gene network.
AB  - Type 2 Diabetes (T2D) constitutes a global health burden. Efforts to uncover
      predisposing genetic variation have been considerable, yet detailed knowledge of
      the underlying pathogenesis remains poor. Here, we constructed a T2D phenotypic
      linkage network (T2D-PLN), by integrating diverse gene functional information
      that highlight genes, which when disrupted in mice, elicit similar T2D-relevant
      phenotypes. Sensitising the network to T2D-relevant phenotypes enabled
      significant functional convergence to be detected between genes implicated in
      monogenic or syndromic diabetes and genes lying within genomic regions associated
      with T2D common risk. We extended these analyses to a recent multiethnic T2D case
      control exome of 12,940 individuals that found no evidence of T2D risk
      association for rare frequency variants outside of previously known T2D risk
      loci. Examining associations involving protein-truncating variants (PTV), most at
      low population frequencies, the T2D-PLN was able to identify a convergent set of
      biological pathways that were perturbed within four of five independent T2D
      case/control ethnic sets of 2000 to 5000 exomes each. These same pathways were
      found to be over-represented among both known monogenic or syndromic diabetes
      genes and genes within T2D-associated common risk loci. Our study demonstrates
      convergent biology amongst variants representing different classes of T2D genetic
      risk. Although convergence was observed at the pathway level, few of the
      contributing genes were found in common between different cohorts or variant
      classes, most notably between the exome variant sets which suggests that future
      rare variant studies may be better focusing their power onto a single population
      of recent common ancestry.

PMID- 29059181
TI  - Magnetoreception-A sense without a receptor.
AB  - Evolution has equipped life on our planet with an array of extraordinary senses,
      but perhaps the least understood is magnetoreception. Despite compelling
      behavioral evidence that this sense exists, the cells, molecules, and mechanisms
      that mediate sensory transduction remain unknown. So how could animals detect
      magnetic fields? We introduce and discuss 3 concepts that attempt to address this
      question: (1) a mechanically sensitive magnetite-based magnetoreceptor, (2) a
      light-sensitive chemical-based mechanism, and (3) electromagnetic induction
      within accessory structures. In discussing the merits and issues with each of
      these ideas, we draw on existing precepts in sensory biology. We argue that
      solving this scientific mystery will require the development of new genetic tools
      in magnetosensitive species, coupled with an interdisciplinary approach that
      bridges physics, behavior, anatomy, physiology, molecular biology, and genetics.

PMID- 29059182
TI  - Profiling RNA-Seq at multiple resolutions markedly increases the number of causal
      eQTLs in autoimmune disease.
AB  - Genome-wide association studies have identified hundreds of risk loci for
      autoimmune disease, yet only a minority (~25%) share genetic effects with changes
      to gene expression (eQTLs) in immune cells. RNA-Seq based quantification at whole
      gene resolution, where abundance is estimated by culminating expression of all
      transcripts or exons of the same gene, is likely to account for this observed
      lack of colocalisation as subtle isoform switches and expression variation in
      independent exons can be concealed. We performed integrative cis-eQTL analysis
      using association statistics from twenty autoimmune diseases (560 independent
      loci) and RNA-Seq data from 373 individuals of the Geuvadis cohort profiled at
      gene-, isoform-, exon-, junction-, and intron-level resolution in lymphoblastoid
      cell lines. After stringently testing for a shared causal variant using both the
      Joint Likelihood Mapping and Regulatory Trait Concordance frameworks, we found
      that gene-level quantification significantly underestimated the number of causal
      cis-eQTLs. Only 5.0-5.3% of loci were found to share a causal cis-eQTL at gene
      level compared to 12.9-18.4% at exon-level and 9.6-10.5% at junction-level. More
      than a fifth of autoimmune loci shared an underlying causal variant in a single
      cell type by combining all five quantification types; a marked increase over
      current estimates of steady-state causal cis-eQTLs. Causal cis-eQTLs detected at
      different quantification types localised to discrete epigenetic annotations. We
      applied a linear mixed-effects model to distinguish cis-eQTLs modulating all
      expression elements of a gene from those where the signal is only evident in a
      subset of elements. Exon-level analysis detected disease-associated cis-eQTLs
      that subtly altered transcription globally across the target gene. We dissected
      in detail the genetic associations of systemic lupus erythematosus and
      functionally annotated the candidate genes. Many of the known and novel genes
      were concealed at gene-level (e.g. IKZF2, TYK2, LYST). Our findings are provided
      as a web resource.

PMID- 29059183
TI  - Machine learning to design integral membrane channelrhodopsins for efficient
      eukaryotic expression and plasma membrane localization.
AB  - There is growing interest in studying and engineering integral membrane proteins
      (MPs) that play key roles in sensing and regulating cellular response to diverse
      external signals. A MP must be expressed, correctly inserted and folded in a
      lipid bilayer, and trafficked to the proper cellular location in order to
      function. The sequence and structural determinants of these processes are complex
      and highly constrained. Here we describe a predictive, machine-learning approach
      that captures this complexity to facilitate successful MP engineering and design.
      Machine learning on carefully-chosen training sequences made by structure-guided
      SCHEMA recombination has enabled us to accurately predict the rare sequences in a
      diverse library of channelrhodopsins (ChRs) that express and localize to the
      plasma membrane of mammalian cells. These light-gated channel proteins of
      microbial origin are of interest for neuroscience applications, where expression
      and localization to the plasma membrane is a prerequisite for function. We
      trained Gaussian process (GP) classification and regression models with
      expression and localization data from 218 ChR chimeras chosen from a 118,098
      variant library designed by SCHEMA recombination of three parent ChRs. We use
      these GP models to identify ChRs that express and localize well and show that our
      models can elucidate sequence and structure elements important for these
      processes. We also used the predictive models to convert a naturally occurring
      ChR incapable of mammalian localization into one that localizes well.

PMID- 29059184
TI  - Wide Distribution and Genetic Diversity of Babesia microti in Small Mammals from
      Yunnan Province, Southwestern China.
AB  - BACKGROUND: Babesia, usually found in wild and domestic mammals worldwide, have
      recently been responsible for emerging malaria-like zoonosis in infected
      patients. Human B. microti infection has been identified in China, primarily in
      the Southwest along the Myanmar border but little direct surveillance of B.
      microti infection in rodents has been carried out here (Yunnan province). In this
      region, a diverse topographic range combined with tropical moisture sustains a
      high biodiversity of small mammals, which might play important role on Babesia
      transmission. METHODS: Small mammals were captured in 141 sample locations from
      18 counties located Yunnan Province, and screened for B. microti-like parasites
      infection by a nested PCR to target 18S rRNA gene of Babesia, plus directly
      sequencing for positive samples. Univariate and multivariate forward stepwise
      logistic regression analysis was used to access the association between
      infections and some related risk factors. RESULTS: Infection with Babesia microti
      was confirmed in 2.4% (53/ 2204) of small mammals. Significant differences in
      prevalence rates of B. microti were observed based on variations in forest,
      agricultural, and residential landscapes. Furthermore, adult small mammals had
      higher prevalence rates than younger, pubertal mammals. The near full-length 18S
      rRNA gene revealed that there were two types of B. microti, Kobe and Otsu, which
      demonstrate the genetic diversity and regional distribution. CONCLUSIONS: There
      exists a wide distribution and genetic diversity of endemic B. microti in
      Southwestern China, warranting further investigations and monitoring of clinical
      disease in individuals presenting with Babesia like symptoms in these areas.

PMID- 29059185
TI  - Decoding brain activity using a large-scale probabilistic functional-anatomical
      atlas of human cognition.
AB  - A central goal of cognitive neuroscience is to decode human brain activity-that
      is, to infer mental processes from observed patterns of whole-brain activation.
      Previous decoding efforts have focused on classifying brain activity into a small
      set of discrete cognitive states. To attain maximal utility, a decoding framework
      must be open-ended, systematic, and context-sensitive-that is, capable of
      interpreting numerous brain states, presented in arbitrary combinations, in light
      of prior information. Here we take steps towards this objective by introducing a
      probabilistic decoding framework based on a novel topic model-Generalized
      Correspondence Latent Dirichlet Allocation-that learns latent topics from a
      database of over 11,000 published fMRI studies. The model produces highly
      interpretable, spatially-circumscribed topics that enable flexible decoding of
      whole-brain images. Importantly, the Bayesian nature of the model allows one to
      "seed" decoder priors with arbitrary images and text-enabling researchers, for
      the first time, to generate quantitative, context-sensitive interpretations of
      whole-brain patterns of brain activity.

PMID- 29059186
TI  - Lymphatic pathology in asymptomatic and symptomatic children with Wuchereria
      bancrofti infection in children from Odisha, India and its reversal with DEC and
      albendazole treatment.
AB  - BACKGROUND: Once interruption of transmission of lymphatic filariasis is
      achieved, morbidity prevention and management becomes more important. A study in
      Brugia malayi filariasis from India has shown sub-clinical lymphatic pathology
      with potential reversibility. We studied a Wuchereria bancrofti infected
      population, the major contributor to LF globally. METHODS: Children aged 5-18
      years from Odisha, India were screened for W. bancrofti infection and disease.
      102 infected children, 50 with filarial disease and 52 without symptoms were
      investigated by lymphoscintigraphy and then randomized to receive a supervised
      single oral dose of DEC and albendazole which was repeated either annually or
      semi-annually. The lymphatic pathology was evaluated six monthly for two years.
      FINDINGS: Baseline lymphoscintigraphy showed abnormality in lower limb lymphatics
      in 80% of symptomatic (40/50) and 63.5% (33/52) of asymptomatic children.
      Progressive improvement in baseline pathology was seen in 70.8, 87.3, 98.6, and
      98.6% of cases at 6, 12, 18, and 24 months follow up, while in 4.2, 22.5, 47.9
      and 64.8%, pathology reverted to normal. This was independent of age (p = 0.27),
      symptomatic status (p = 0.57) and semi-annual/bi-annual dosing (p = 0.46). Six of
      eleven cases showed clinical reduction in lymphedema of legs. INTERPRETATION: A
      significant proportion of a young W. bancrofti infected population exhibited
      lymphatic pathology which was reversible with annual dosage of DEC and
      albendazole. This provides evidence for morbidity prevention & treatment of early
      lymphedema. It can also be used as a tool to improve community compliance during
      mass drug administration. TRIAL REGISTRATION: ClinicalTrials.gov No
      CTRI/2013/10/004121.

PMID- 29059187
TI  - Correction: The WAGR syndrome gene PRRG4 is a functional homologue of the
      commissureless axon guidance gene.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006865.].

PMID- 29059188
TI  - Intraspecific variation in feeding strategies of Galapagos sea lions: A case of
      trophic specialization.
AB  - The trophic behavior of marine predators varies according to the level of
      competition to which they are exposed. In general, populations that inhabit lower
      productivity systems face a strong intraspecific competition, which contributes
      to the development of different foraging strategies to maximize nutritional
      efficiency. Given the high trophic flexibility of Zalophus wollebaeki, this
      species is considered appropriate for the analysis of such behavior. Furthermore,
      this trophic flexibility has allowed them to persist in a seemingly marginal
      ecosystem. In this study, we used a comparative analysis of variables (diet and
      dive behavior) related to Z. wollebaeki trophic niche plasticity to better
      understand their foraging ecology, using techniques such scat analysis, satellite
      telemetry and complementarily an isotopic analysis. Scat analysis revealed intra
      population variation in their diet, represented by prey from different
      environments (epipelagic and benthic). These results are supported by the
      animals' locations at sea and diving profiles. Global Positioning System (GPS)
      and time-depth recorder (TDR) records showed the existence of two groups, with
      differing feeding areas and diving behavior. Also the delta15N values showed
      differences in the trophic level at which the species fed. These results
      constitute a relevant finding in the evolutionary behavior of the species,
      showing that Z. wollebaeki has developed a high degree of foraging flexibility,
      thus increasing its survival rate in an ecosystem that is highly demanding in
      terms of resource availability.

PMID- 29059189
TI  - Inhibition of miR-142-5P ameliorates disease in mouse models of experimental
      colitis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are epigenetically involved in regulating gene
      expression. They may be of importance in the pathogenesis of inflammatory bowel
      disease (IBD). The aim of this study was to determine the role of miRNAs by their
      specific blocking in the CD4+CB45RBhi T-cell transfer model of chronic
      experimental colitis. METHODS: Colitis caused by transfer of WT CD4+CD45RBhi T
      cells in severe combined immunodeficiency (SCID) mice shares many features with
      human IBD. Colonic miRNA expression levels were measured at three time points in
      colitic mice, where a time-dependent upregulation of multiple miRNAs was seen. To
      inhibit these miRNAs, specific locked-nucleic-acid-modified (LNA)
      oligonucleotides were administered in further experiments at the moment the mice
      demonstrated the first signs of colitis. As controls, PBS and a scrambled
      sequence of anti-miRNA were used. Genome-wide expression analyses were also
      performed in order to detect candidate target genes of miR-142-5p, of which
      inhibition resulted in most effective amelioration of colitis. RESULTS: Anti-miR
      142-5p reduced colitis and related wasting disease when administered in the T
      cell transfer model, reflected in reduced weight loss and a lower disease
      activity index (DAI). In further validation experiments we also observed a higher
      survival rate and less colonic histological inflammation in the antagomir-treated
      mice. Moreover, by genome-wide expression analyses, we found downstream
      activation of the anti-inflammatory IL10RA pathway, including three genes also
      found in the top-20 candidate target genes of miR-142-5p. CONCLUSION: In
      conclusion, CD4+CD45RBhi-transfer colitis induces miR-142-5p. Blocking miR-142-5p
      reduced colitis and prevented wasting disease, possibly by activation of the
      IL10RA pathway.

PMID- 29059190
TI  - Cluster randomized trial comparing school-based mass drug administration
      schedules in areas of western Kenya with moderate initial prevalence of
      Schistosoma mansoni infections.
AB  - BACKGROUND: Mass drug administration (MDA) using praziquantel is the WHO
      recommended approach for control of schistosomiasis. However, few studies have
      compared the impact of different schedules of MDA on the resultant infection
      levels. We wished to evaluate whether annual MDA was more effective than less
      frequent treatments for reducing community-level prevalence and intensity of
      Schistosoma mansoni infections. METHODS: We performed a cluster randomized trial
      (ISRCTN 14849830) of 3 different MDA frequencies over a 5 year period in 75
      villages with moderate (10%-24%) initial prevalence of S. mansoni in school
      children in western Kenya. Praziquantel was distributed by school teachers to
      students either annually, the first 2 years, or every other year over a 4 year
      period. Prevalence and intensity of infection were measured by stool examination
      in 9-12 year old students using the Kato-Katz method at baseline, each treatment
      year, and for the final evaluation at year 5. S. mansoni prevalence and intensity
      were also measured in first year students at baseline and year 5. RESULTS: Twenty
      five schools were randomly assigned to each arm. S. mansoni prevalence and
      infection intensity in 9-12 year old students significantly decreased within each
      arm from baseline to year 5 but there were no differences between arms. There
      were no differences in infection levels in first year students either within or
      between arms. CONCLUSIONS: Strategies employing 2 or 4 rounds of MDA had a
      similar impact in schools with moderate initial prevalence, suggesting that
      schistosomiasis control can be sustained by school-based MDA, even if provided
      only every other year.

PMID- 29059192
TI  - Correction: Chlamydomonas DYX1C1/PF23 is essential for axonemal assembly and
      proper morphology of inner dynein arms.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006996.].

PMID- 29059191
TI  - Validation of a pregnancy planning measure for Arabic-speaking women.
AB  - BACKGROUND: The prevalence of unplanned pregnancy in Saudi Arabia has not been
      thoroughly investigated. OBJECTIVE: To conduct a psychometric evaluation study of
      the Arabic version of the London Measure of Unplanned Pregnancy (LMUP). METHODS:
      To evaluate the psychometric properties of the LMUP, we conducted a self
      administered online survey among 796 ever-married Saudi women aged 20-49 years,
      and a re-test survey among 24 women. The psychometric properties evaluated
      included content validity measured by content validity index (CVI), structural
      validity assessed by exploratory factor analysis (EFA), substantive validity
      assessed by hypothesis testing, contextual stability for the test-retest assessed
      by weighted Kappa, and internal consistency assessed by Cronbach's alpha.
      RESULTS: The psychometric analysis of the Arabic version of LMUP exhibited valid
      and reliable properties. The CVIs for individual items and at the scale level
      were >0.7. EFA confirmed a unidimensional extraction of the scale item.
      Hypothesis testing confirmed expected associations. The tool was stable with
      weighted kappa = 0.78 and Cronbach's alpha = 0.88. CONCLUSION AND
      RECOMMENDATIONS: In this study, the validity and reliability of the Arabic
      version of the LMUP were confirmed according to well-known psychometric criteria.
      This LMUP version can be used in research studies among Arabic-speaking women to
      measure unplanned pregnancy and investigate correlates and outcomes related to
      unplanned pregnancy.

PMID- 29059193
TI  - Safe corridor for the implantation of thoracolumbar pedicle screws in growing
      pigs: A morphometric study.
AB  - The pig spine is widely used as a large animal model for preclinical research in
      human medicine to test new spinal implants and surgical procedures. Among them,
      pedicle screw is one of the most common method of fixation of those implants.
      However, the pedicle of the porcine vertebra is not as well defined and not as
      large as the pedicle of the human vertebra. Therefore, the position of the screw
      should be adapted to the pig and not merely transposed based on the literature on
      humans. The purpose of this study is to determine the characteristics of the
      optimum implantation corridors for pedicle screws in the thoracolumbar spine of
      piglets of different ages using computed tomography (CT) and to determine the
      size and length of these corridors in pigs of different ages. CT scans from five
      groups of age: 6, 10, 14, 18, and 26 weeks were reviewed. For each thoracolumbar
      vertebrae, the pedicle width, pedicle axis length, and the pedicle angle was
      measured for the left and right pedicle. A total of 326 thoracic vertebrae and
      126 lumbar vertebrae were included in the study. Pedicles are statistically
      larger but not longer for the lumbar vertebrae. An important variation of the
      pedicle angle is observed along the spine. In all pigs, an abrupt modification of
      the pedicle angle between T10 and T11 was observed, which corresponds to the
      level of the anticlinal vertebra which is the vertebra for which the spinous
      process is nearly perpendicular to the vertebral body. In conclusion, this study
      provides a quantitative database of pedicle screw implantation corridors in pigs
      of different ages. When using pedicle screws in experimental studies in pigs,
      these results should be considered for selecting the most suitable implants for
      the study but also to ensure a correct and safer screw position. Improving study
      procedures may limit postoperative complications and pain, thereby limiting the
      use of live animals.

PMID- 29059194
TI  - Role of Neuropilin-1/Semaphorin-3A signaling in the functional and morphological
      integrity of the cochlea.
AB  - Neuropilin-1 (Nrp1) encodes the transmembrane cellular receptor neuropilin-1,
      which is associated with cardiovascular and neuronal development and was within
      the peak SNP interval on chromosome 8 in our prior GWAS study on age-related
      hearing loss (ARHL) in mice. In this study, we generated and characterized an
      inner ear-specific Nrp1 conditional knockout (CKO) mouse line because Nrp1
      constitutive knockouts are embryonic lethal. In situ hybridization demonstrated
      weak Nrp1 mRNA expression late in embryonic cochlear development, but increased
      expression in early postnatal stages when cochlear hair cell innervation patterns
      have been shown to mature. At postnatal day 5, Nrp1 CKO mice showed disorganized
      outer spiral bundles and enlarged microvessels of the stria vascularis (SV) but
      normal spiral ganglion cell (SGN) density and presynaptic ribbon body counts;
      however, we observed enlarged SV microvessels, reduced SGN density, and a
      reduction of presynaptic ribbons in the outer hair cell region of 4-month-old
      Nrp1 CKO mice. In addition, we demonstrated elevated hearing thresholds of the 2
      month-old and 4-month-old Nrp1 CKO mice at frequencies ranging from 4 to 32kHz
      when compared to 2-month-old mice. These data suggest that conditional loss of
      Nrp1 in the inner ear leads to progressive hearing loss in mice. We also
      demonstrated that mice with a truncated variant of Nrp1 show cochlear axon
      guidance defects and that exogenous semaphorin-3A, a known neuropilin-1 receptor
      agonist, repels SGN axons in vitro. These data suggest that Neuropilin
      1/Semaphorin-3A signaling may also serve a role in neuronal pathfinding in the
      developing cochlea. In summary, our results here support a model whereby
      Neuropilin-1/Semaphorin-3A signaling is critical for the functional and
      morphological integrity of the cochlea and that Nrp1 may play a role in ARHL.

PMID- 29059196
TI  - Exogenous dietary lysozyme improves the growth performance and gut microbiota in
      broiler chickens targeting the antioxidant and non-specific immunity mRNA
      expression.
AB  - Supplementation of exogenous enzymes in chickens has been widely practiced, yet
      mechanisms responsible are not fully delineated. To investigate the effects of
      the dietary lysozyme on the growth performance and immunity of broiler chickens,
      a total of 120 one-day-old Ross 308 chicks were randomly allocated into four
      groups, each having three replicates (30 birds/group). The chicks were fed the
      starter (1-21 d) and grower (22-35 d) diets supplemented with 0 (control), 70
      (LYZ70), 90 (LYZ90) and 120 (LYZ120) g of lysozyme 10%(r) per ton of basal diet
      for five weeks. The results revealed significant improvement in the growth
      performance and gut environment. There were significant decreases (P < 0.05 or
      0.01) in the harmful fecal Coliform and Clostridia and an increase (P ? 0.05) in
      the beneficial Lactobacillus in the lysozyme-supplemented groups, especially in
      LYZ90. Moreover, the mRNA expressions of Cu, Zn-superoxide dismutase (SOD1),
      glutathione peroxidase (GSH-Px), interferon-gamma (IFN-gamma), interleukin-10 (IL
      10), and interleukin-18 (IL-18) were upregulated in response to lysozyme
      supplementation. In comparison to control, LYZ90 fed birds had a significant
      increase (P < 0.01) in the GSH-Px gene expression that enhances the antioxidant
      status of the gut. Expression of the biomarkers involved in the gut non-specific
      immunity indicated significant increases in the mRNA expression of INF-gamma (P <
      0.001), IL-10 (P < 0.001), and IL-18 (P < 0.05) in LYZ90 group. Also, serum
      globulin levels were significantly elevated (P ? 0.05) in lysozyme-supplemented
      groups. Histologically, the intestinal villi length and crypts depth were also
      enhanced (P ? 0.05) by dietary lysozyme supplementation. In conclusion,
      supplementation of broiler chickens with exogenous lysozyme, especially at 90 g
      of lysozyme per ton of basal diet dose rate, improved the growth performance, gut
      antioxidant status, and nonspecific immunity of broiler chickens.

PMID- 29059195
TI  - Strongyloides stercoralis is associated with significant morbidity in rural
      Cambodia, including stunting in children.
AB  - BACKGROUND: Strongyloides stercoralis is a soil-transmitted nematode that can
      replicate within its host, leading to long-lasting and potentially fatal
      infections. It is ubiquitous and highly prevalent in Cambodia. The extent of
      morbidity associated with S. stercoralis infection is difficult to assess due to
      the broad spectrum of symptoms and, thus, remains uncertain.
      METHODOLOGY/PRINCIPAL FINDINGS: Clinical signs were compared among S. stercoralis
      infected vs. non-infected participants in a cross-sectional survey conducted in
      2012 in eight villages of Northern Cambodia, and before and after treatment with
      a single oral dose of ivermectin (200MUg/kg BW) among participants harboring S.
      stercoralis. Growth retardation among schoolchildren and adolescents was assessed
      using height-for-age and thinness using body mass index-for-age. S. stercoralis
      prevalence was 31.1% among 2,744 participants. Urticaria (55% vs. 47%, OR: 1.4,
      95% CI: 1.1-1.6) and itching (52% vs. 48%, OR: 1.2, 95% CI: 1.0-1.4) were more
      frequently reported by infected participants. Gastrointestinal, dermatological,
      and respiratory symptoms were less prevalent in 103 mono-infected participants
      after treatment. Urticaria (66% vs. 11%, OR: 0.03, 95% CI: 0.01-0.1) and
      abdominal pain (81 vs. 27%, OR: 0.07, 95% CI: 0.02-0.2) mostly resolved by
      treatment. S. stercoralis infection was associated with stunting, with 2.5-fold
      higher odds in case of heavy infection. CONCLUSIONS/SIGNIFICANCE: The morbidity
      associated with S. stercoralis confirmed the importance of gastrointestinal and
      dermatological symptoms unrelated to parasite load, and long-term chronic effects
      when associated with malnutrition. The combination of high prevalence and
      morbidity calls for the integration of S. stercoralis into ongoing STH control
      measures in Cambodia.

PMID- 29059197
TI  - An email-based intervention to improve the number and timeliness of letters sent
      from the hospital outpatient clinic to the general practitioner: A pair
      randomized controlled trial.
AB  - OBJECTIVE: Letters from the hospital to the general practitioner are important
      for maintaining continuity of care. Although doctors feel letters are important,
      they are often not written on time. To improve the number and timeliness of
      letters sent from the hospital outpatient department to the general practitioner
      using an email-based intervention evaluated in a randomized controlled trial.
      MATERIALS AND METHODS: Users were interviewed to determine the requirements for
      the intervention. Due to high between-doctor variation at baseline, doctors were
      matched for baseline performance and pair-randomized. The effectiveness of the
      intervention was assessed using meta-analytic methods. The primary outcome was
      the number of patient visits which should have generated a letter that had a
      letter by 90 days after the visit. Satisfaction was assessed with an anonymous
      survey. RESULTS: The intervention consisted of a monthly email reminder for each
      doctor containing a list of his or her patients who were (over)due for a letter.
      Doctors in the intervention group had 21% fewer patient visits which did not have
      a letter by 90 days (OR = 5.7, p = 0.0020). Satisfaction with the system was very
      high. DISCUSSION: This study examines the effect of a simple reminder in absence
      of other interventions, and provides an example of an effective non-interruptive
      decision support intervention. CONCLUSION: A simple email reminder improved the
      number and timeliness of letters from the outpatient department to the general
      practitioner, and was viewed as a useful service by its users.

PMID- 29059198
TI  - Optimal stride frequencies in running at different speeds.
AB  - During running at a constant speed, the optimal stride frequency (SF) can be
      derived from the u-shaped relationship between SF and heart rate (HR). Changing
      SF towards the optimum of this relationship is beneficial for energy expenditure
      and may positively change biomechanics of running. In the current study, the
      effects of speed on the optimal SF and the nature of the u-shaped relation were
      empirically tested using Generalized Estimating Equations. To this end, HR was
      recorded from twelve healthy (4 males, 8 females) inexperienced runners, who
      completed runs at three speeds. The three speeds were 90%, 100% and 110% of self
      selected speed. A self-selected SF (SFself) was determined for each of the speeds
      prior to the speed series. The speed series started with a free-chosen SF
      condition, followed by five imposed SF conditions (SFself, 70, 80, 90, 100
      strides.min-1) assigned in random order. The conditions lasted 3 minutes with 2.5
      minutes of walking in between. SFself increased significantly (p<0.05) with speed
      with averages of 77, 79, 80 strides.min-1 at 2.4, 2.6, 2.9 m.s-1, respectively).
      As expected, the relation between SF and HR could be described by a parabolic
      curve for all speeds. Speed did not significantly affect the curvature, nor did
      it affect optimal SF. We conclude that over the speed range tested, inexperienced
      runners may not need to adapt their SF to running speed. However, since SFself
      were lower than the SFopt of 83 strides.min-1, the runners could reduce HR by
      increasing their SFself.

PMID- 29059199
TI  - Effectiveness of beta-blockers depending on the genotype of congenital long-QT
      syndrome: A meta-analysis.
AB  - BACKGROUND: Beta-blockers are first-line therapy in patients with congenital long
      QT syndrome (LQTS). OBJECTIVE: This study sought to determine the differences in
      effectiveness of beta-blockers on risk reduction according to LQTS genotype.
      METHODS: We searched MEDLINE, EMBASE, and CENTRAL databases to investigate the
      use of beta-blockers (atenolol, nadolol, propranolol, and metoprolol) in patients
      with LQTS. Hazard ratio (HR) and relative risk (RR) were extracted or calculated
      from studies reporting cardiac events (syncope, aborted cardiac arrest (ACA), or
      sudden cardiac death (SCD)). RESULTS: Among 2,113 articles searched, 10 studies
      (7 registry-based cohort studies (Cohort) and 3 interrupted time series studies
      (ITS)) involving 9,727 patients were included. In a meta-analysis using a random
      effect model, the use of beta-blocker was associated with significant risk
      reduction of all cardiac events (HR 0.49, p<0.001 in Cohort; RR 0.39, p<0.001 in
      ITS) and serious cardiac events (ACA or SCD) (HR 0.47, p<0.001 in Cohort). In
      both LQT1 and LQT2, the risk was reduced with beta-blocker therapy in Cohort (HR
      0.59 in LQT1; HR 0.39 in LQT2) as well as ITS (RR 0.29 in LQT1; RR 0.48 in LQT2).
      Among the beta-blockers, nadolol showed a significant risk reduction in both LQT1
      and LQT2 (HR 0.47 and 0.27, respectively), whereas atenolol and propranolol
      decreased the risk only in LQT1 (HR 0.36 and 0.46, respectively). Metoprolol
      showed no significant reduction in either genotype. In LQT3, beta-blocker therapy
      was not as effective as LQT1 or LQT2; however, it was inconclusive due to data
      insufficiency. CONCLUSION: This meta-analysis showed that beta-blockers were
      effective in reducing risk of cardiac events in patients with LQTS. Among them,
      nadolol was effective in LQT1 and LQT2, whereas other drugs showed different
      effectiveness depending on LQT genotype.

PMID- 29059200
TI  - De novo RNA sequencing transcriptome of Rhododendron obtusum identified the early
      heat response genes involved in the transcriptional regulation of photosynthesis.
AB  - Rhododendron spp. is an important ornamental species that is widely cultivated
      for landscape worldwide. Heat stress is a major obstacle for its cultivation in
      south China. Previous studies on rhododendron principally focused on its
      physiological and biochemical processes, which are involved in a series of stress
      tolerance. However, molecular or genetic properties of rhododendron's response to
      heat stress are still poorly understood. The phenotype and chlorophyll
      fluorescence kinetics parameters of four rhododendron cultivars were compared
      under normal or heat stress conditions, and a cultivar with highest heat
      tolerance, "Yanzhimi" (R. obtusum) was selected for transcriptome sequencing. A
      total of 325,429,240 high quality reads were obtained and assembled into 395,561
      transcripts and 92,463 unigenes. Functional annotation showed that 38,724
      unigenes had sequence similarity to known genes in at least one of the proteins
      or nucleotide databases used in this study. These 38,724 unigenes were
      categorized into 51 functional groups based on Gene Ontology classification and
      were blasted to 24 known cluster of orthologous groups. A total of 973 identified
      unigenes belonged to 57 transcription factor families, including the stress
      related HSF, DREB, ZNF, and NAC genes. Photosynthesis was significantly enriched
      in the Kyoto Encyclopedia of Genes and Genomes pathway, and the changed
      expression pattern was illustrated. The key pathways and signaling components
      that contribute to heat tolerance in rhododendron were revealed. These results
      provide a potentially valuable resource that can be used for heat-tolerance
      breeding.

PMID- 29059201
TI  - Comparison of fMRI paradigms assessing visuospatial processing: Robustness and
      reproducibility.
AB  - The development of brain imaging techniques, in particular functional magnetic
      resonance imaging (fMRI), made it possible to non-invasively study the
      hemispheric lateralization of cognitive brain functions in large cohorts.
      Comprehensive models of hemispheric lateralization are, however, still missing
      and should not only account for the hemispheric specialization of individual
      brain functions, but also for the interactions among different lateralized
      cognitive processes (e.g., language and visuospatial processing). This calls for
      robust and reliable paradigms to study hemispheric lateralization for various
      cognitive functions. While numerous reliable imaging paradigms have been
      developed for language, which represents the most prominent left-lateralized
      brain function, the reliability of imaging paradigms investigating typically
      right-lateralized brain functions, such as visuospatial processing, has received
      comparatively less attention. In the present study, we aimed to establish an fMRI
      paradigm that robustly and reliably identifies right-hemispheric activation
      evoked by visuospatial processing in individual subjects. In a first study, we
      therefore compared three frequently used paradigms for assessing visuospatial
      processing and evaluated their utility to robustly detect right-lateralized brain
      activity on a single-subject level. In a second study, we then assessed the test
      retest reliability of the so-called Landmark task-the paradigm that yielded the
      most robust results in study 1. At the single-voxel level, we found poor
      reliability of the brain activation underlying visuospatial attention. This
      suggests that poor signal-to-noise ratios can become a limiting factor for test
      retest reliability. This represents a common detriment of fMRI paradigms
      investigating visuospatial attention in general and therefore highlights the need
      for careful considerations of both the possibilities and limitations of the
      respective fMRI paradigm-in particular, when being interested in effects at the
      single-voxel level. Notably, however, when focusing on the reliability of
      measures of hemispheric lateralization (which was the main goal of study 2), we
      show that hemispheric dominance (quantified by the lateralization index, LI, with
      |LI| >0.4) of the evoked activation could be robustly determined in more than 62%
      and, if considering only two categories (i.e., left, right), in more than 93% of
      our subjects. Furthermore, the reliability of the lateralization strength (LI)
      was "fair" to "good". In conclusion, our results suggest that the degree of right
      hemispheric dominance during visuospatial processing can be reliably determined
      using the Landmark task, both at the group and single-subject level, while at the
      same time stressing the need for future refinements of experimental paradigms and
      more sophisticated fMRI data acquisition techniques.

PMID- 29059202
TI  - Projections of non-communicable disease and health care costs among HIV-positive
      persons in Italy and the U.S.A.: A modelling study.
AB  - BACKGROUND: Country-specific forecasts of the growing non-communicable disease
      (NCD) burden in ageing HIV-positive patients will be key to guide future HIV
      policies. We provided the first national forecasts for Italy and the Unites
      States of America (USA) and quantified direct cost of caring for these
      increasingly complex patients. METHODS AND SETTING: We adapted an individual
      based model of ageing HIV-positive patients to Italy and the USA, which followed
      patients on HIV-treatment as they aged and developed NCDs (chronic kidney
      disease, diabetes, dyslipidaemia, hypertension, non-AIDS malignancies, myocardial
      infarctions and strokes). The models were parameterised using data on 7,469 HIV
      positive patients from the Italian Cohort Naive to Antiretrovirals Foundation
      Study and 3,748 commercially-insured patients in the USA and extrapolated to
      national level using national surveillance data. RESULTS: The model predicted
      that mean age of HIV-positive patients will increase from 46 to 59 in Italy and
      from 49 to 58 in the USA in 2015-2035. The proportion of patients in Italy and
      the USA diagnosed with >=1 NCD is estimated to increase from 64% and 71% in 2015
      to 89% and 89% by 2035, respectively, driven by moderate cardiovascular disease
      (CVD) (hypertension and dyslipidaemia), diabetes and malignancies in both
      countries. NCD treatment costs as a proportion of total direct HIV costs will
      increase from 11% to 23% in Italy and from 40% to 56% in the USA in 2015-2035.
      CONCLUSIONS: HIV patient profile in Italy and the USA is shifting to older
      patients diagnosed with multiple co-morbidity. This will increase NCD treatment
      costs and require multi-disciplinary patient management.

PMID- 29059203
TI  - Continuous high and low temperature induced a decrease of photosynthetic activity
      and changes in the diurnal fluctuations of organic acids in Opuntia
      streptacantha.
AB  - Opuntia plants grow naturally in areas where temperatures are extreme and highly
      variable in the day during the entire year. These plants survive through
      different adaptations to respond to adverse environmental conditions. Despite
      this capability, it is unknown how CAM photosynthetic activity and growth in
      Opuntia plantlets is affected by constant heat or cold. Therefore, the main
      objective of this research was to evaluate the short-term effect of high (40
      degrees C) and low (4 degrees C) continuous temperatures on the photosynthetic
      efficiency, the organic acid content (malic acid) and the relative growth rate
      (RGR) in seven-month-old Opuntia streptacantha plantlets during 5, 10, and 15
      days. Chlorophyll fluorescence analysis allowed us to determine that high
      temperatures negatively impact the photosynthetic efficiency of O. streptacantha
      plantlets, which exhibited the lowest values of maximum quantum efficiency of the
      photosystem II (Fv/Fm = 52%, Fv/F0 = 85%), operational quantum yield of PS
      (PhiPSII = 65%) and relative electron transport rate (rETR = 65%), as well as
      highest values of basal fluorescence (F0 = 226%) during 15 days of treatment.
      Similarly, low temperatures decreased Fv/Fm (16%), Fv/F0 (50%), PhiPSII and rETR
      (16%). High temperatures also decreased nocturnal acidification in approximately
      34-50%, whereas low temperatures increased it by 30-36%. Additionally, both
      continuous temperatures affected drastically diurnal consumption of malic acid,
      which was related to a significant RGR inhibition, where the specific
      photosynthetic structure area component was the most affected. Our results
      allowed determining that, despite the high tolerance to extreme temperatures
      described for Opuntia plants, young individuals of O. streptacantha suffered
      photosynthetic impairment that led to the inhibition of their growth. Thus, the
      main findings reported in this study can help to predict the potential impact of
      climatic change on the establishment and survival of succulent species of arid
      and semiarid regions of Mexico.

PMID- 29059204
TI  - Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency.
AB  - BACKGROUND: Sirtuins are NAD+ dependent deacetylases, which regulate
      mitochondrial energy metabolism as well as cellular response to stress. The
      NAD/NADH-system plays a crucial role in oxidative phosphorylation linking
      sirtuins and the mitochondrial respiratory chain. Furthermore, sirtuins are able
      to directly deacetylate and activate different complexes of the respiratory
      chain. This prompted us to analyse sirtuin levels in skin fibroblasts from
      patients with cytochrome c-oxidase (COX) deficiency and to test the impact of
      different pharmaceutical activators of sirtuins (SRT1720, paeonol) to modulate
      sirtuins and possibly respiratory chain enzymes in patient cells in vitro.
      METHODS: We assayed intracellular levels of sirtuin 1 and the mitochondrial
      sirtuins SIRT3 and SIRT4 in human fibroblasts from patients with COX- deficiency.
      Furthermore, sirtuins were measured after inhibiting complex IV in healthy
      control fibroblasts by cyanide and after incubation with activators SRT1720 and
      paeonol. To determine the effect of sirtuin inhibition at the cellular level we
      measured total cellular acetylation (control and patient cells, with and without
      treatment) by Western blot. RESULTS: We observed a significant decrease in
      cellular levels of all three sirtuins at the activity, protein and
      transcriptional level (by 15% to 50%) in COX-deficient cells. Additionally, the
      intracellular concentration of NAD+ was reduced in patient cells. We mimicked the
      biochemical phenotype of COX- deficiency by incubating healthy fibroblasts with
      cyanide and observed reduced sirtuin levels. A pharmacological activation of
      sirtuins resulted in normalized sirtuin levels in patient cells. Hyper
      acetylation was also reversible after treatment with sirtuin activators.
      Pharmacological modulation of sirtuins resulted in altered respiratory chain
      complex activities. CONCLUSIONS: We found inhibition of situins 1, 3 and 4 at
      activity, protein and transcriptional levels in fibroblasts from patient with COX
      deficiency. Pharmacological activators were able to restore reduced sirtuin
      levels and thereby modulate respiratory chain activities.

PMID- 29059205
TI  - Determinants of dog owner-charged rabies vaccination in Kinshasa, Democratic
      Republic of Congo.
AB  - Rabies is a preventable fatal disease that causes about 61,000 human deaths
      annually around the world, mostly in developing countries. In Africa, several
      studies have shown that vaccination of pets is effective in controlling the
      disease. An annual vaccination coverage of 70% is recommended by the World Health
      Organization as a control threshold. The effective control of rabies requires
      vaccination coverage of owned dogs. Identification of the factors determining dog
      owners' choice to vaccinate is necessary for evidence-based policy-making.
      However, for the Democratic Republic of Congo (DRC), the limited data on rabies
      vaccination coverage makes it difficult for its control and formulation of
      appropriate policies. A cross-sectional study was conducted in Kinshasa (Lemba
      commune) with dog-owning households and owned dogs as study populations. The
      association between dog vaccination and independent factors (household socio
      demographics characteristics, dog characteristics, knowledge of rabies and
      location of veterinary offices/clinics) was performed with Epi-info 7. The Odds
      Ratio (OR) and p-value < 0.05 were used to determine levels of significance. A
      total of 166 households owning dogs and 218 owned dogs were investigated. 47% of
      the dogs had been vaccinated within one year preceding the survey which is higher
      than the critical coverage (25 to 40%) necessary to interrupt rabies transmission
      but below the 70% threshold recommended by WHO for control. The determinants of
      vaccination included socio-economic level of the household (OR = 2.9, p<0.05),
      formal education level of the dog owner (OR = 4, p<0.05), type of residence (OR =
      4.6, p<0.05), knowledge of rabies disease (OR = 8.0, p<0.05), knowledge of
      location of veterinary offices/clinics (OR = 3.4, p<0.05), dog gender (OR = 1.6,
      p<0.05) and dog breed (OR = 2.1, p<0.05). This study shows that the vaccination
      coverage in this area can easily reach the WHO threshold if supplemented by mass
      vaccination campaigns.

PMID- 29059206
TI  - Use of immunohistochemical biomarkers as independent predictor of neoplastic
      progression in Barrett's oesophagus surveillance: A systematic review and meta
      analysis.
AB  - INTRODUCTION: The low incidence of oesophageal adenocarcinoma (EAC) in Barrett's
      oesophagus (BE) patients reinforces the need for risk stratification tools to
      make BE surveillance more effective. Therefore, we have undertaken a systematic
      review and meta-analysis of published studies on immunohistochemical (IHC)
      biomarkers in BE to determine the value of IHC biomarkers as neoplastic
      predictors in BE surveillance. MATERIALS AND METHODS: We searched MEDLINE,
      EMBASE, Web of Science, CENTRAL, Pubmed publisher, and Google scholar. All
      studies on IHC biomarkers in BE surveillance were included. ORs were extracted
      and meta-analyses performed with a random effects model. RESULTS: 16 different
      IHC biomarkers were studied in 36 studies. These studies included 425 cases and
      1835 controls. A meta- analysis was performed for p53, aspergillus oryzae lectin
      (AOL), Cyclin A, Cyclin D and alpha-methylacyl-CoA racemase. Aberrant p53
      expression was significantly associated with an increased risk of neoplastic
      progression with an OR of 3.18 (95% CI 1.68 to 6.03). This association was
      confirmed for both non-dysplastic BE and BE with low-grade dysplasia (LGD).
      Another promising biomarker to predict neoplastic progression was AOL, with an OR
      of 3.04 (95% CI 2.05 to 4.49). DISCUSSION: Use of p53 IHC staining may improve
      risk stratification in BE surveillance. Aberrant p53 expression in BE patients
      appeared to be associated with a significantly increased risk of neoplastic
      progression for both non-dysplastic and LGD BE patients.

PMID- 29059207
TI  - Targeting mesothelin receptors with drug-loaded bacterial nanocells suppresses
      human mesothelioma tumour growth in mouse xenograft models.
AB  - Human malignant mesothelioma is a chemoresistant tumour that develops from
      mesothelial cells, commonly associated with asbestos exposure. Malignant
      mesothelioma incidence rates in European countries are still rising and Australia
      has one of the highest burdens of malignant mesothelioma on a population basis in
      the world. Therapy using systemic delivery of free cytotoxic agents is associated
      with many undesirable side effects due to non-selectivity, and is thus dose
      limited which limits its therapeutic potential. Therefore, increasing the
      selectivity of anti-cancer agents has the potential to dramatically enhance drug
      efficacy and reduce toxicity. EnGeneIC Dream Vectors (EDV) are antibody-targeted
      nanocells which can be loaded with cytotoxic drugs and delivered to specific
      cancer cells via bispecific antibodies (BsAbs) which target the EDV and a cancer
      cell-specific receptor, simultaneously. BsAbs were designed to target doxorubicin
      loaded EDVs to cancer cells via cell surface mesothelin (MSLN). Flow cytometry
      was used to investigate cell binding and induction of apoptosis, and confocal
      microscopy to visualize internalization. Mouse xenograft models were used to
      assess anti-tumour effects in vivo, followed by immunohistochemistry for ex vivo
      evaluation of proliferation and necrosis. BsAb-targeted, doxorubicin-loaded EDVs
      were able to bind to and internalize within mesothelioma cells in vitro via MSLN
      receptors and induce apoptosis. In mice xenografts, the BsAb-targeted,
      doxorubicin-loaded EDVs suppressed the tumour growth and also decreased cell
      proliferation. Thus, the use of MSLN-specific antibodies to deliver encapsulated
      doxorubicin can provide a novel and alternative modality for treatment of
      mesothelioma.

PMID- 29059208
TI  - Psychological well-being in elderly adults with extraordinary episodic memory.
AB  - OBJECTIVES: The Northwestern University SuperAging Program studies a rare cohort
      of individuals over age 80 with episodic memory ability at least as good as
      middle-age adults to determine what factors contribute to their elite memory
      performance. As psychological well-being is positively correlated with cognitive
      performance in older adults, the present study examined whether aspects of
      psychological well-being distinguish cognitive SuperAgers from their cognitively
      average-for-age, same-age peers. METHOD: Thirty-one SuperAgers and 19 cognitively
      average-for-age peers completed the Ryff 42-item Psychological Well-Being
      questionnaire, comprised of 6 subscales: Autonomy, Positive Relations with
      Others, Environmental Mastery, Personal Growth, Purpose in Life, and Self
      Acceptance. RESULTS: The groups did not differ on demographic factors, including
      estimated premorbid intelligence. Consistent with inclusion criteria, SuperAgers
      had better episodic memory scores. Compared to cognitively average-for-age peers,
      SuperAgers endorsed greater levels of Positive Relations with Others. The groups
      did not differ on other PWB-42 subscales. DISCUSSION: While SuperAgers and their
      cognitively average-for-age peers reported similarly high levels of psychological
      well-being across multiple dimensions, SuperAgers endorsed greater levels of
      positive social relationships. This psychological feature could conceivably have
      a biological relationship to the greater thickness of the anterior cingulate
      gyrus and higher density of von Economo neurons previously reported in
      SuperAgers.

PMID- 29059209
TI  - Neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial
      ovarian cancer: A meta-analysis of peri-operative outcome.
AB  - OBJECTIVE: To assess whether neoadjuvant chemotherapy (NACT) is superior to
      primary debulking surgery (PDS) with regard to optimal cytoreduction, peri
      operative morbidity, mortality, and quality of life (QOL) in advanced epithelial
      ovarian cancer (EOC). METHODS: We searched the PubMed, Embase, Cochrane Central
      Register of Controlled Trials, Web of Science, Registers of Clinical Trials for
      randomized controlled trials (RCTs) comparing NACT to PDS in women with
      Federation of International Gynaecologists and Obstetricians stage III-IV EOC.
      RevMan 5.3 software was utilized for statistical analysis. RESULTS: Four RCTs
      involving 1,607 women with advanced EOC were included. Compared with PDS, NACT
      provided a higher rate of complete cytoreduction (risk ratio [RR], 1.95; 95%
      confidence interval [CI], 1.33 to 2.87), optimal cytoreduction (RR: 1.61 [95%CI:
      1.05 to 2.47]), but there was no significant difference in residual disease 0-1
      cm (p = 0.49). NACT was associated with lower peri-operative morbidity with
      respect to infection (RR: 0.30 [95% CI: 0.16 to 0.56]), gastrointestinal fistula
      (RR: 0.24 [95% CI: 0.06 to 0.95]), any grade 3 or 4 adverse event (RR: 0.29 [95%
      CI: 0.11 to 0.78]), and less post-surgical death within 28 days (RR: 0.14 [95%
      CI: 0.04 to 0.49]). NACT provided better QOL in terms of fatigue (weight mean
      difference [WMD], -3.28; [95% CI: -3.99 to -2.57]), role functioning (WMD: 5.29
      [95% CI: 4.44 to 6.14]), emotional functioning (WMD: 6.19 [95% CI: 5.57 to
      6.82]), and cognitive functioning (WMD: 1.02 [95% CI: 0.43 to 1.61]) at 6-month
      follow-up compared with PDS. CONCLUSIONS: NACT is associated with superior
      optimal cytoreduction, lower peri-operative morbidity as well as post-surgical
      mortality, and better QOL compared to initial surgery in patients with advanced
      EOC. Future research should focus on improving the efficacy of NACT.

PMID- 29059210
TI  - Measures of cardiovascular autonomic activity in insomnia disorder: A systematic
      review.
AB  - BACKGROUND: Insomnia disorder is a widespread sleep disorder with a prevalence of
      approximately 10%. Even though the link between insomnia and cardiovascular
      activity is not exactly clear, it is generally assumed that cardiovascular
      autonomic modifications could occur as a result of sleeplessness, or,
      alternatively, that autonomic alterations could be an expression of a hyper
      arousal state. This review investigates whether cardiovascular measures are
      different between insomniacs and controls. METHODS: Electronic databases were
      systematically searched, and 34 studies were identified. Heart rate variability
      features, the association of cardiac and EEG activity, physiologic complexity
      measures, and cardiovascular activity, assessed by measures such as pre-ejection
      time, blood pressure, and heart rate dynamics were studied. Given the
      heterogeneity of the studies, a narrative synthesis of the findings was
      performed. RESULTS: This review study found overall differences in cardiovascular
      activity between insomniacs and controls in most of the observational studies
      (21/26), while the expression of cardiovascular regulation varied between the
      examined insomniac groups. All the studies that investigated the association of
      cardiac activity and EEG power reported an altered relation between autonomic
      activity and EEG parameters in insomniacs. CONCLUSION: Autonomic regulation tends
      to be consistent between insomniacs, as long as they are grouped according to
      their respective phenotype, as shown in the insomnia subgroup with objectively
      short sleep duration. Our hypothesis is that these differences in the expression
      of cardiovascular activity could be explained by the heterogeneity of the
      disorder. Therefore, the determination of insomnia phenotypes, and the study of
      cardiovascular measures, rather than heart rate variability alone, will give more
      insight into the link between insomnia and cardiovascular regulation. This study
      suggests that cardiovascular activity differs between insomniacs and controls.
      These new findings are of interest to clinicians and researchers for a more
      accurate insomnia assessment, and the development of personalized technological
      solutions in insomnia.

PMID- 29059211
TI  - Screening differential miRNAs responsible for permeability increase in HUVECs
      infected with influenza A virus.
AB  - Severe influenza infections are featured by acute lung injury, a syndrome of
      increased pulmonary microvascular permeability. A growing number of evidences
      have shown that influenza A virus induces cytoskeletal rearrangement and
      permeability increase in endothelial cells. Although miRNA's involvement in the
      regulation of influenza virus infection and endothelial cell (EC) function has
      been well documented, little is known about the miRNA profiles in influenza
      infected endothelial cells. Using human umbilical vein endothelial cells (HUVECs)
      as cell models, the present study aims to explore the differential miRNAs in
      influenza virus-infected ECs and analyze their target genes involved in EC
      permeability regulation. As the results showed, permeability increased and F
      actin cytoskeleton reorganized after HUVECs infected with influenza A virus (CA07
      or PR8) at 30 MOI. MicroRNA microarray revealed a multitude of miRNAs
      differentially expressed in HUVECs after influenza virus infection. Through
      target gene prediction, we found that a series of miRNAs were involved in PKC,
      Rho/ROCK, HRas/Raf/MEK/ERK, and Ca2+/CaM pathways associated with permeability
      regulation, and most of these miRNAs were down-regulated after flu infection. It
      has been reported that PKC, Rho/ROCK, HRas/Raf/MEK/ERK, and Ca2+/CaM pathways are
      activated by flu infection and play important roles in permeability regulation.
      Therefore, the cumulative effects of these down-regulated miRNAs which
      synergistically enhanced activation of PKC, Rho/ROCK, Ras/Raf/MEK/ERK, and
      Ca2+/CaM pathways, can eventually lead to actin rearrangement and
      hyperpermeability in flu-infected HUVECs.

PMID- 29059212
TI  - De novo transcriptome sequencing of two cultivated jute species under salinity
      stress.
AB  - Soil salinity, a major environmental stress, reduces agricultural productivity by
      restricting plant development and growth. Jute (Corchorus spp.), a commercially
      important bast fiber crop, includes two commercially cultivated species,
      Corchorus capsularis and Corchorus olitorius. We conducted high-throughput
      transcriptome sequencing of 24 C. capsularis and C. olitorius samples under salt
      stress and found 127 common differentially expressed genes (DEGs); additionally,
      4489 and 492 common DEGs were identified in the root and leaf tissues,
      respectively, of both Corchorus species. Further, 32, 196, and 11 common
      differentially expressed transcription factors (DTFs) were detected in the leaf,
      root, or both tissues, respectively. Several Gene Ontology (GO) terms were
      enriched in NY and YY. A Kyoto Encyclopedia of Genes and Genomes analysis
      revealed numerous DEGs in both species. Abscisic acid and cytokinin signal
      pathways enriched respectively about 20 DEGs in leaves and roots of both NY and
      YY. The Ca2+, mitogen-activated protein kinase signaling and oxidative
      phosphorylation pathways were also found to be related to the plant response to
      salt stress, as evidenced by the DEGs in the roots of both species. These results
      provide insight into salt stress response mechanisms in plants as well as a basis
      for future breeding of salt-tolerant cultivars.

PMID- 29059213
TI  - Endothelial CaMKII as a regulator of eNOS activity and NO-mediated
      vasoreactivity.
AB  - The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a
      serine/threonine kinase important in transducing intracellular Ca2+ signals.
      While in vitro data regarding the role of CaMKII in the regulation of endothelial
      nitric oxide synthase (eNOS) are contradictory, its role in endothelial function
      in vivo remains unknown. Using two novel transgenic models to express CaMKII
      inhibitor peptides selectively in endothelium, we examined the effect of CaMKII
      on eNOS activation, NO production, vasomotor tone and blood pressure. Under
      baseline conditions, CaMKII activation was low in the aortic wall. Consistently,
      systolic and diastolic blood pressure, heart rate and plasma NO levels were
      unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII
      inhibition had no significant effect on NO-dependent vasodilation. These results
      were confirmed in studies of aortic rings transduced with adenovirus expressing a
      CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment
      produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS
      activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179
      and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO
      production in vitro were decreased under CaMKII inhibition. Our results
      demonstrate that CaMKII plays an important role in transient bradykinin-driven
      eNOS activation in vitro, but does not regulate NO production, vasorelaxation or
      blood pressure in vivo under baseline conditions.

PMID- 29059214
TI  - Effect of glycemic control and type of diabetes treatment on unsuccessful TB
      treatment outcomes among people with TB-Diabetes: A systematic review.
AB  - BACKGROUND: Stringent glycemic control by using insulin as a replacement or in
      addition to oral hypoglycemic agents (OHAs) has been recommended for people with
      tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO
      2016:CRD42016039101) analyses whether this improves TB treatment outcomes.
      OBJECTIVES: Among people with drug-susceptible TB and DM on anti-TB treatment, to
      determine the effect of i) glycemic control (stringent or less stringent)
      compared to poor glycemic control and ii) insulin (only or with OHAs) compared to
      'OHAs only' on unsuccessful TB treatment outcome(s). We looked for unfavourable
      TB treatment outcomes at the end of intensive phase and/or end of TB treatment
      (minimum six months and maximum 12 months follow up). Secondary outcomes were
      development of MDR-TB during the course of treatment, recurrence after 6 months
      and/or after 1 year post successful treatment completion and development of
      adverse events related to glucose lowering treatment (including hypoglycemic
      episodes). METHODS: All interventional studies (with comparison arm) and cohort
      studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM
      treatment details and TB treatment outcomes were eligible. We searched electronic
      databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and
      April 2017. Screening, data extraction and risk of bias assessment were done
      independently by two investigators and recourse to a third investigator, for
      resolution of differences. RESULTS: After removal of duplicates from 2326
      identified articles, 2054 underwent title and abstract screening. Following full
      text screening of 56 articles, nine cohort studies were included. Considering
      high methodological and clinical heterogeneity, we decided to report the results
      qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic
      control, of which only two were free of the risk of bias (with confounder
      adjusted measures of effect). An Indian study reported 30% fewer unsuccessful
      treatment outcomes (aOR (0.95 CI): 0.72 (0.64-0.81)) and 2.8 times higher odds of
      'no recurrence' (aOR (0.95 CI): 2.83 (2.60-2.92)) among patients with optimal
      glycemic control at baseline. A Peruvian study reported faster culture conversion
      among those with glycemic control (aHR (0.95 CI): 2.2 (1.1,4)). Two poor quality
      studies reported the effect of insulin on TB treatment outcomes. CONCLUSION: We
      identified few studies that were free of the risk of bias. There were limited
      data and inconsistent findings among available studies. We recommend robustly
      designed and analyzed studies including randomized controlled trials on the
      effect of glucose lowering treatment options on TB treatment outcomes.

PMID- 29059215
TI  - DNA metabarcoding reveals diverse diet of the three-spined stickleback in a
      coastal ecosystem.
AB  - The three-spined stickleback (Gasterosteus aculeatus L., hereafter 'stickleback')
      is a common mesopredatory fish in marine, coastal and freshwater areas. In large
      parts of the Baltic Sea, stickleback densities have increased >10-fold during the
      last decades, and it is now one of the dominating fish species both in terms of
      biomass and effects on lower trophic levels. Still, relatively little is known
      about its diet-knowledge which is essential to understand the increasing role
      sticklebacks play in the ecosystem. Fish diet analyses typically rely on visual
      identification of stomach contents, a labour-intensive method that is made
      difficult by prey digestion and requires expert taxonomic knowledge. However,
      advances in DNA-based metabarcoding methods promise a simultaneous identification
      of most prey items, even from semi-digested tissue. Here, we studied the diet of
      stickleback from the western Baltic Sea coast using both DNA metabarcoding and
      visual analysis of stomach contents. Using the cytochrome oxidase (CO1) marker we
      identified 120 prey taxa in the diet, belonging to 15 phyla, 83 genera and 84
      species. Compared to previous studies, this is an unusually high prey diversity.
      Chironomids, cladocerans and harpacticoids were dominating prey items. Large
      sticklebacks were found to feed more on benthic prey, such as amphipods,
      gastropods and isopods. DNA metabarcoding gave much higher taxonomic resolution
      (median rank genus) than visual analysis (median rank order), and many taxa
      identified using barcoding could not have been identified visually. However, a
      few taxa identified by visual inspection were not revealed by barcoding. In
      summary, our results suggest that the three-spined stickleback feeds on a wide
      variety of both pelagic and benthic organisms, indicating that the strong
      increase in stickleback populations may affect many parts of the Baltic Sea
      coastal ecosystem.

PMID- 29059216
TI  - Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters.
AB  - Oral mucositis (OM) is an important side effect of cancer treatment,
      characterized by ulcerative lesions in the mucosa of patients undergoing
      radiotherapy or chemotherapy, which has marked effects on patient quality of life
      and cancer therapy continuity. Considering that few protocols have demonstrated
      efficacy in preventing this side effect, the aim of this study was to examine the
      effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters
      by studying signaling pathways. OM was induced in hamsters by 5-FU followed by
      mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The
      experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg).
      Macroscopic, histopathological, and immunohistochemical analyses as well as
      immunofluorescence experiments were performed on the oral mucosa of the animals.
      The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and
      quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg)
      reduced inflammation and ulceration of the oral mucosa of hamsters. In addition,
      DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, and macrophage migration inhibitory factor (MIF). DEX (1
      mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix
      metalloproteinase (MMP)-2, transforming growth factor (TGF)-beta, MIF, Smad 2/3,
      Smad 2/3 phosphorylated and NFkappaB p65 in the jugal mucosa. Finally, DEX (1
      mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M),
      glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein
      kinase (MKP1) gene expression and reduced NFkappaB p65 and serine threonine
      kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM
      induced by 5-FU in hamsters.

PMID- 29059217
TI  - Prohibition of antibiotic growth promoters has affected the genomic profiles of
      Lactobacillus salivarius inhabiting the swine intestine.
AB  - After the introduction of a ban on the use of antibiotic growth promoters (AGPs)
      for livestock, the feeding environment, including the composition of animal
      intestinal microbiota, has changed rapidly. We hypothesized that the microbial
      genomes have also been affected by this legal prohibition, and investigated an
      important member of the swine gut microbiota, Lactobacillus salivarius, with a
      pan-genomic approach. Here, we isolated 21 L. salivarius strains composed of 6
      strains isolated before the AGP prohibition (SBPs) and 15 strains isolated after
      the AGP prohibition (SAPs) at an interval of a decade, and the draft genomes were
      generated de novo. Several genomic differences between SBPs and SAPs were
      identified, although the number and function of antibiotic resistance genes were
      not different. SBPs showed larger genome size and a higher number of orthologs,
      as well as lower genetic diversity, than SAPs. SBPs had genes associated with the
      utilization of L-rhamnose and D-tagatose for energy production. Because these
      sugars are also used in exopolysaccharide (EPS) synthesis, we tried to identify
      differences in biofilm formation-associated genes. The genes for the production
      of EPSs and extracellular proteins were different in terms of amino acid
      sequences. Indeed, SAPs formed dense biofilm and survived better than SBPs in the
      swine intestinal environment. These results suggest that SAPs have evolved and
      adapted to protect themselves from new selection pressure of the swine intestinal
      microenvironment by forming dense biofilms, adopting a distinct antibiotic
      resistance strategy. This finding is particularly important to understand the
      evolutionary changes in host-microbe interaction and provide detailed insight for
      the development of effective probiotics for livestock.

PMID- 29059218
TI  - Mapping and predictive variations of soil bacterial richness across France.
AB  - Although numerous studies have demonstrated the key role of bacterial diversity
      in soil functions and ecosystem services, little is known about the variations
      and determinants of such diversity on a nationwide scale. The overall objectives
      of this study were i) to describe the bacterial taxonomic richness variations
      across France, ii) to identify the ecological processes (i.e. selection by the
      environment and dispersal limitation) influencing this distribution, and iii) to
      develop a statistical predictive model of soil bacterial richness. We used the
      French Soil Quality Monitoring Network (RMQS), which covers all of France with
      2,173 sites. The soil bacterial richness (i.e. OTU number) was determined by
      pyrosequencing 16S rRNA genes and related to the soil characteristics, climatic
      conditions, geomorphology, land use and space. Mapping of bacterial richness
      revealed a heterogeneous spatial distribution, structured into patches of about
      111km, where the main drivers were the soil physico-chemical properties (18% of
      explained variance), the spatial descriptors (5.25%, 1.89% and 1.02% for the
      fine, medium and coarse scales, respectively), and the land use (1.4%). Based on
      these drivers, a predictive model was developed, which allows a good prediction
      of the bacterial richness (R2adj of 0.56) and provides a reference value for a
      given pedoclimatic condition.

PMID- 29059219
TI  - The fate of lysine: Non-targeted stable isotope analysis reveals parallel ways
      for lysine catabolization in Phaeobacter inhibens.
AB  - For a detailed investigation of the degradation of lysine in Phaeobacter inhibens
      DSM 17395, stable isotope experiments with uniformly 13C labeled L-lysine were
      carried out with lysine adapted cells and the metabolites were analyzed using
      GC/MS and HPLC/MS. A non-targeted stable isotope analysis was used which compares
      labeled and not labeled samples to determine the Mass Isotopomer Distribution not
      only for known metabolites but for all labeled compounds in our GC/MS analysis.
      We show that P. inhibens uses at least two parallel pathways for the first
      degradation steps of lysine. Further investigations identified L-pipecolate as an
      L-lysine degradation intermediate in P. inhibens. The analysis of HPLC/MS data as
      well as the labeling data of tricarboxylic acid (TCA) cycle intermediates show
      that L-lysine is not only catabolized directly to acetyl-CoA but also via the
      ethylmalonyl-CoA-pathway, leading to entry points into the TCA cycle via acetyl
      CoA, succinyl-CoA, and malate. Altogether the presented data give a detailed
      insight into the catabolization of L-lysine following the fate of 13C labeled
      carbon via several ways into the TCA cycle.

PMID- 29059220
TI  - Statistical analysis for masked hybrid system lifetime data in step-stress
      partially accelerated life test with progressive hybrid censoring.
AB  - In this paper, we investigate a step-stress partially accelerated lifetime test
      for the four-component hybrid systems with Type-II progressive hybrid censoring
      scheme while the life time of system component follows exponential failure rate.
      In many cases, the exact component causing the system failure cannot be
      identified and the cause of failure is masked. Based on Type-II progressively
      hybrid censored and masked data, the maximum likelihood estimations for unknown
      parameters and acceleration factor are obtained. In addition, approximate
      confidence interval and bootstrap confidence interval are presented by using the
      asymptotic distributions of the maximum likelihood estimations for unknown
      parameters and bootstrap method, respectively. Finally, the proposed method is
      illustrated through the simulation studies.

PMID- 29059221
TI  - Reduction in skeletal muscle fibrosis of spontaneously hypertensive rats after
      laceration by microRNA targeting angiotensin II receptor.
AB  - Regeneration of injured skeletal muscles is affected by fibrosis, which can be
      improved by the administration of angiotensin II (AngII) receptor (ATR) blockers
      in normotensive animals. However, the role of ATR in skeletal muscle fibrosis in
      hypertensive organisms has not been investigated yet. The tibialis anterior (TA)
      muscle of spontaneously hypertensive (SHR) and Wistar rats (WR) were lacerated
      and a lentivector encoding a microRNA targeting AngII receptor type 1 (At1) (Lv
      mirAT1a) or control (Lv-mirCTL) was injected. The TA muscles were collected after
      30 days to evaluate fibrosis by histology and gene expression by real-time
      quantitative PCR (RT-qPCR) and Western blot. SHR's myoblasts were analyzed by RT
      qPCR, 48 h after transduction. In the SHR's TA, AT1 protein expression was 23.5
      fold higher than in WR without injury, but no difference was observed in the
      angiotensin II receptor type 2 (AT2) protein expression. TA laceration followed
      by suture (LS) produced fibrosis in the SHR (23.3+/-8.5%) and WR (7.9+/-1.5%). Lv
      mirAT1 treatment decreased At1 gene expression in 50% and reduced fibrosis to 7%
      30 days after. RT-qPCR showed that reduction in At1 expression is due to
      downregulation of the At1a but not of the At1b. RT-qPCR of myoblasts from SHR
      transduced with Lv-mirAT1a showed downregulation of the Tgf-b1, Tgf-b2, Smad3,
      Col1a1, and Col3a1 genes by mirAT1a. In vivo and in vitro studies indicate that
      hypertension overproduces skeletal muscle fibrosis, and AngII-AT1a signaling is
      the main pathway of fibrosis in SHR. Moreover, muscle fibrosis can be treated
      specifically by in loco injection of Lv-mirAT1a without affecting other organs.

PMID- 29059222
TI  - Correction: Enhanced Gene Expression Rather than Natural Polymorphism in Coding
      Sequence of the OsbZIP23 Determines Drought Tolerance and Yield Improvement in
      Rice Genotypes.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0150763.].

PMID- 29059223
TI  - Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving
      postoperative pain in a rat model.
AB  - This study evaluates the sustained analgesic effect of ketorolac-eluting
      thermosensitive biodegradable hydrogel in the plantar incisional pain model of
      the rat hind-paw. A ketorolac-embedded 2, 2'-Bis (2-oxazolin) (BOX) linking
      methoxy-poly(ethylene glycol) and poly(lactide-co-glycolide) (mPEG-PLGA) diblock
      copolymer (BOX copolymer) was synthesized as keto-hydrogel based on optimal sol
      gel phase transition and in vitro drug release profile. The effect of keto
      hydrogel on postoperative pain (POP) was assessed using the established plantar
      incisional pain model in hind-paw of rats and compared to that of ketorolac
      solution. Pain and sensory threshold, as well as pain scoring, were evaluated
      with behavioral tests by means of anesthesiometer and incapacitance apparatus,
      respectively. Pro-inflammatory cytokine levels (TNF-alpha, IL-6, VEGF, and IL
      1beta) around incisional wounds were measured by ELISA. Tissue histology was
      assessed using hematoxylin and eosin and Masson's trichrome staining. Ten mg/mL
      (25 wt%) keto-hydrogel showed a sol-gel transition at 26.4 degrees C with a 10
      day sustained drug release profile in vitro. Compared to ketorolac solution
      group, the concentration of ketorolac in tissue fluid was higher in the keto
      hydrogel group during the first 18 h of application. Keto-hydrogel elevated pain
      and sensory threshold, increased weight-bearing capacity, and significantly
      reduced the levels of TNF-alpha, IL-6, and IL-1beta while enhanced VEGF in tissue
      fluid. Histologic analysis reveals greater epithelialization and collagen
      deposition around wound treated with keto-hydrogel. In conclusion, our study
      suggests that keto-hydrogel is an ideal compound to treat POP with a secondary
      gain of improved incisional wound healing.

PMID- 29059225
TI  - Adaptation to dislodgement risk on wave-swept rocky shores in the snail Littorina
      saxatilis.
AB  - The periwinkle Littorina saxatilis has repeatedly evolved both a small, fragile
      and globose "wave ecotype" confined to wave-swept shores and a large, robust and
      elongated "crab ecotype" found in nearby crab-rich but less-exposed shores. This
      phenotypic divergence is assumed to reflect, in some part, local adaptation to
      wave exposure, but this hypothesis has received incomplete experimental testing.
      Here, we report a test of the prediction that the wave ecotype has a higher
      capacity to resist water flow than the crab ecotype. We sampled snails along a
      crab-wave transect and measured their resistance to dislodgement in a high-speed
      water flume with water speeds that match those of breaking waves in a range of
      relevant field conditions. Snails from the wave environment were consistently
      more resistant to water flow than snails from the crab environment and high
      resistance was positively correlated with the surface area of the foot and the
      area of the outer aperture contour both relative to shell size, and to the extent
      of lateral shell compression. In a separate experiment, we found that snails
      raised in still water in a common garden showed higher resistance to water flow
      if originating from a wave environment than from a crab environment, and this was
      true both at juvenile (2 weeks) and adult (10 months) developmental stages. This
      result suggests genetic control of a distinct "wave adapted" phenotype, likely to
      be maintained under strong divergent selection between the two adjacent habitats.

PMID- 29059224
TI  - Netrin-1 is a novel regulator of vascular endothelial function in diabetes.
AB  - BACKGROUND: Netrin-1, a secreted laminin-like protein identified as an axon
      guidance molecule, has been shown to be of critical importance in the
      cardiovascular system. Recent studies have revealed pro-angiogenic, anti
      apoptotic and anti-inflammatory properties of netrin-1 as well as
      cardioprotective actions against myocardial injury in diabetic mice. AIM: To
      examine the role of netrin-1 in diabetes-and high glucose (HG)-induced vascular
      endothelial dysfunction (VED) using netrin-1 transgenic mice (Tg3) and cultured
      bovine aortic endothelial cells (BAEC). MAIN OUTCOME: Overexpression of netrin-1
      prevented diabetes-induced VED in aorta from diabetic mice and netrin-1 treatment
      attenuated HG-induced impairment of nitric oxide synthase (NOS) function in
      BAECs. METHODS AND RESULTS: Experiments were performed in Tg3 and littermate
      control (WT) mice rendered diabetic with streptozotocin (STZ) and in BAECs
      treated with HG (25 mmol/L). Levels of netrin-1 and its receptor DCC, markers of
      inflammation and apoptosis and vascular function were assessed in aortas from
      diabetic and non-diabetic Tg3 and WT mice. Vascular netrin-1 in WT mice was
      reduced under diabetic conditions. Aortas from non-diabetic Tg3 and WT mice
      showed similar maximum endothelium-dependent relaxation (MEDR) (83% and 87%,
      respectively). MEDR was markedly impaired in aorta from diabetic WT mice (51%).
      This effect was significantly blunted in Tg3 diabetic aortas (70%). Improved
      vascular relaxation in Tg3 diabetic mice was associated with increased levels of
      phospho-ERK1/2 and reduced levels of oxidant stress, NFkappaB, COX-2, p16INK4A,
      cleaved caspase-3 and p16 and p53 mRNA. Netrin-1 treatment prevented the HG
      induced decrease in NO production and elevation of oxidative stress and apoptosis
      in BAECs. CONCLUSIONS: Diabetes decreases aortic levels of netrin-1. However,
      overexpression of netrin-1 attenuates diabetes-induced VED and limits the
      reduction of NO levels, while increasing expression of p-ERK1/2, and suppressing
      oxidative stress and inflammatory and apoptotic processes. Enhancement of netrin
      1 function may be a useful therapeutic means for preventing vascular dysfunction
      in diabetes.

PMID- 29059226
TI  - Successful selection of rainbow trout (Oncorhynchus mykiss) on their ability to
      grow with a diet completely devoid of fishmeal and fish oil, and correlated
      changes in nutritional traits.
AB  - In the context of limited marine resources, the exponential growth of aquaculture
      requires the substitution of fish oil and fishmeal, the traditional components of
      fish feeds by terrestrial plant ingredients. High levels of such substitution are
      known to negatively impact fish performance such as growth and survival in
      rainbow trout (Oncorhynchus mykiss) as in other salmonids. In this respect,
      genetic selection is a key enabler for improving those performances and hence for
      the further sustainable development of aquaculture. We selected a rainbow trout
      line over three generations for its ability to survive and grow on a 100% plant
      based diet devoid of both fish oil and fishmeal (V diet) from the very first
      meal. In the present study, we compared the control line and the selected line
      after 3 generations of selection, both fed either the V diet or a marine
      resources-based diet (M diet). The objective of the study was to assess the
      efficiency of selection and the consequences on various correlated nutritional
      traits: feed intake, feed efficiency, digestibility, composition of whole fish,
      nutrient retention and fatty acid (FA) profile. We demonstrated that the genetic
      variability present in our rainbow trout population can be selected to improve
      survival and growth. The major result of the study is that after only three
      generations of selection, selected fish fed the V diet grew at the same rate as
      the control line fed the M diet, whilst the relative reduction of body weight was
      36.8% before the selection. This enhanced performance on the V diet seems to be
      mostly linked to a higher feed intake for the selected fish.

PMID- 29059227
TI  - Exergaming: Feels good despite working harder.
AB  - Strategies to encourage exercise have led to research on cycle ergometer
      'exergaming', as a means of enhancing exercise enjoyment. This research has
      typically prescribed the exercise intensity and used one exercise mode. The aim
      of this study was to compare self-selected exercise intensity on a cycle
      ergometer with and without exergaming modes activated. A total of 20 participants
      aged between 18-40 years (M = 24.2 +/- 5.9) completed a sub-maximal exercise
      test. Participants returned two days later to complete one 45 minute session of
      self-selected exercise with 15 minutes in each of 'control' (standard ergometer),
      'track', and 'game' modes, with order randomized. Heart rate, work rate,
      perceived exertion, and affective valence were recorded during exercise.
      Dissociation and enjoyment were recorded in the rest interval between each mode.
      Participants exercised above ventilatory threshold (VT) in all three modes
      (track, M = 9.5 +/- 12%; game, M = 6.2 +/- 12%; and control, M = 4.4 +/- 14%
      above VT) and at higher work rates (P < 0.05) exergaming (track, M = 94.5 +/-
      27.9; game, M = 96.2 +/- 32.8 watts) than control (M = 86.6 +/- 26.5 watts).
      Despite exercising at a higher intensity, participants perceived exercise during
      the exergaming modes to be most pleasant (P < 0.01), with greater enjoyment (P <
      0.01) and dissociation (P < 0.01) in the game than track mode, and both modes
      higher on these variables than the control mode. Findings support the use of
      exergaming as a strategy to encourage individuals to exercise, with participants
      choosing to work harder physiologically, but reporting more positive
      psychological responses during and following the exercise.

PMID- 29059228
TI  - Retraction: Enhancement of Lipid Productivity in Oleaginous Colletotrichum Fungus
      through Genetic Transformation Using the Yeast CtDGAT2b Gene under Model
      Optimized Growth Condition.

PMID- 29059229
TI  - Association between a history of periodontitis and the risk of systemic lupus
      erythematosus in Taiwan: A nationwide, population-based, case-control study.
AB  - OBJECTIVE: To examine the association between a history of periodontitis (PD) and
      incident systemic lupus erythematosus (SLE). METHODS: We used 2003-2012 claims
      data from the Taiwanese National Health Insurance Database to identify 7,204
      incident SLE patients during 2007-2012 as the study group, along with randomly
      selecting 72,040 non-SLE patients matched (1:10) for age, gender, and first
      diagnosis date (index date) as the control group. The correlation between PD and
      SLE risk was estimated using conditional logistic regression analysis, after
      making adjustments for confounders (including a history of diabetes and number of
      non-PD related dental visits before the index date). To evaluate the effects of
      PD severity and the lag time which occurred since the last PD visit on SLE
      development, odds ratios (ORs) with 95% confidence intervals (CIs) were
      calculated for subgroups of patients with PD according to their number of visits,
      cumulative cost and also the time gaps between their last PD-related visit and
      the index date. RESULTS: A statistically significant association between a
      history of PD and newly diagnosed SLE was observed (OR, 1.21; 95% CI, 1.14-1.28;
      p-value, <0.001). The association was both dose- and time-dependent and was found
      to be strongest when the interval between the last PD-related visit and the index
      date was less than three months (OR, 1.83; 95% CI, 1.61-2.09; p-value, <0.001).
      The association between PD exposure and SLE risk was consistently significant
      among subgroups stratified based on age, gender, or DM status. CONCLUSIONS: The
      results of this nationwide, population-based, case-control study suggest that
      there is a significant association between a history of PD and incident SLE in
      Taiwan. This weak association is limited to lack of information on individual
      smoking status in the database.

PMID- 29059230
TI  - A structural explanation for the low effectiveness of the seasonal influenza H3N2
      vaccine.
AB  - The effectiveness of the annual influenza vaccine has declined in recent years,
      especially for the H3N2 component, and is a concern for global public health. A
      major cause for this lack in effectiveness has been attributed to the egg-based
      vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA)
      often arise during virus passaging that change its antigenicity and hence vaccine
      effectiveness. Here, we characterize the effect of a prevalent substitution,
      L194P, in egg-passaged H3N2 viruses. X-ray structural analysis reveals that this
      substitution surprisingly increases the mobility of the 190-helix and neighboring
      regions in antigenic site B, which forms one side of the receptor binding site
      (RBS) and is immunodominant in recent human H3N2 viruses. Importantly, the L194P
      substitution decreases binding and neutralization by an RBS-targeted broadly
      neutralizing antibody by three orders of magnitude and significantly changes the
      HA antigenicity as measured by binding of human serum antibodies. The receptor
      binding mode and specificity are also altered to adapt to avian receptors during
      egg passaging. Overall, these findings help explain the low effectiveness of the
      seasonal vaccine against H3N2 viruses, and suggest that alternative approaches
      should be accelerated for producing influenza vaccines as well as isolating
      clinical isolates.

PMID- 29059231
TI  - Leader evaluation and team cohesiveness in the process of team development: A
      matter of gender?
AB  - Leadership positions are still stereotyped as masculine, especially in male
      dominated fields (e.g., engineering). So how do gender stereotypes affect the
      evaluation of leaders and team cohesiveness in the process of team development?
      In our study participants worked in 45 small teams (4-5 members). Each team was
      headed by either a female or male leader, so that 45 leaders (33% women)
      supervised 258 team members (39% women). Over a period of nine months, the teams
      developed specific engineering projects as part of their professional
      undergraduate training. We examined leaders' self-evaluation, their evaluation by
      team members, and team cohesiveness at two points of time (month three and month
      nine, the final month of the collaboration). While we did not find any gender
      differences in leaders' self-evaluation at the beginning, female leaders
      evaluated themselves more favorably than men at the end of the projects.
      Moreover, female leaders were evaluated more favorably than male leaders at the
      beginning of the project, but the evaluation by team members did not differ at
      the end of the projects. Finally, we found a tendency for female leaders to build
      more cohesive teams than male leaders.

PMID- 29059232
TI  - Leukemia-associated gene MLAA-34 reduces arsenic trioxide-induced apoptosis in
      HeLa cells via activation of the Wnt/beta-catenin signaling pathway.
AB  - Our laboratory previously used the SEREX method in U937 cells and identified a
      novel leukemia-associated gene MLAA-34, a novel splice variant of CAB39L
      associated with acute monocytic leukemia, that exhibited anti-apoptotic
      activities in U937 cells. Whether MLAA-34 has an anti-apoptotic role in other
      tumor cells has not yet been reported. We explored whether MLAA-34 exhibited anti
      apoptotic effects in HeLa cervical cancer cells and the possible mechanism of
      action. We generated a HeLa cell line stably expressing MLAA-34 and found that
      MLAA-34 overexpression had no effect on the growth, apoptosis and cell cycle of
      HeLa cells. However, upon treatment with arsenic trioxide (ATO) to induce
      apoptosis, the cell viability and colony formation ability of ATO-treated MLAA-34
      stable HeLa cells were significantly higher than that of ATO-treated controls,
      and the apoptosis rate and proportion of G2/M cells also decreased. We found that
      ATO treatment of HeLa cells resulted in significant decreases in the expression
      of beta-catenin mRNA and protein and the downstream target factors c-Myc, cyclin
      B1, and cyclin D1 in the Wnt signaling pathway. Notably, ATO-treated MLAA-34
      stable HeLa cells showed a significant reduction in the ATO-mediated
      downregulation of these factors. In addition, MLAA-34 overexpression
      significantly increased the expression of nuclear beta-catenin protein in ATO
      treated cells compared with HeLa cells treated only with ATO. Thus, here we have
      found that the Wnt/beta-catenin signaling pathway is involved in ATO-induced
      apoptosis in HeLa cells. MLAA-34 reduces ATO-induced apoptosis and G2/M arrest,
      and the anti-apoptotic effect may be achieved by activating the Wnt/beta-catenin
      signaling pathway in HeLa cells.

PMID- 29059233
TI  - Business cycles' correlation and systemic risk of the Japanese supplier-customer
      network.
AB  - This work aims to study and explain the business cycle correlations of the
      Japanese production network. We consider the supplier-customer network, which is
      a directed network representing the trading links between Japanese firms (links
      from suppliers to customers). The community structure of this network is
      determined by applying the Infomap algorithm. Each community is defined by its
      GDP and its associated business cycle. Business cycle correlations between
      communities are estimated based on copula theory. Then, based on firms'
      attributes and network topology, these correlations are explained through linear
      econometric models. The results show strong evidence of business cycle
      correlations in the Japanese production network. A significant systemic risk is
      found for high negative or positive shocks. These correlations are explained
      mainly by the sector and by geographic similarities. Moreover, our results
      highlight the higher vulnerability of small communities and small firms, which is
      explained by the disassortative mixing of the production network.

PMID- 29059234
TI  - Neonicotinoid pesticides can reduce honeybee colony genetic diversity.
AB  - Neonicotinoid insecticides can cause a variety of adverse sub-lethal effects in
      bees. In social species such as the honeybee, Apis mellifera, queens are
      essential for reproduction and colony functioning. Therefore, any negative effect
      of these agricultural chemicals on the mating success of queens may have serious
      consequences for the fitness of the entire colony. Queens were exposed to the
      common neonicotinoid pesticides thiamethoxam and clothianidin during their
      developmental stage. After mating, their spermathecae were dissected to count the
      number of stored spermatozoa. Furthermore, their worker offspring were genotyped
      with DNA microsatellites to determine the number of matings and the genotypic
      composition of the colony. Colonies providing the male mating partners were also
      inferred. Both neonicotinoid and control queens mated with drones originating
      from the same drone source colonies, and stored similar number of spermatozoa.
      However, queens reared in colonies exposed to both neonicotinoids experienced
      fewer matings. This resulted in a reduction of the genetic diversity in their
      colonies (i.e. higher intracolonial relatedness). As decreased genetic diversity
      among worker bees is known to negatively affect colony vitality, neonicotinoids
      may have a cryptic effect on colony health by reducing the mating frequency of
      queens.

PMID- 29059235
TI  - Creation of a pediatric mature B-cell non-Hodgkin lymphoma cohort within the
      Pediatric Health Information System Database.
AB  - Mature B-cell non-Hodgkin lymphoma (B-NHL) constitutes a collection of relatively
      rare pediatric malignancies. In order to utilize administrative data to perform
      large-scale epidemiologic studies within this population, a two-step process was
      used to assemble a 12-year cohort of B-NHL patients treated between 2004 and 2015
      within the Pediatric Health Information System database. Patients were identified
      by ICD-9 codes, and their chemotherapy data were then manually reviewed against
      standard B-NHL treatment regimens. A total of 1,409 patients were eligible for
      cohort inclusion. This process was validated at a single center, utilizing both
      an institutional tumor registry and medical record review as the gold standards.
      The validation demonstrated appropriate sensitivity (91.5%) and positive
      predictive value (95.1%) to allow for the future use of this cohort for
      epidemiologic and comparative effectiveness research.

PMID- 29059236
TI  - Effect of iRoot Fast Set root repair material on the proliferation, migration and
      differentiation of human dental pulp stem cells in vitro.
AB  - The present study investigated the effect of iRoot Fast Set root repair material
      (iRoot FS) on the proliferation, migration and differentiation of human dental
      pulp stem cells (hDPSCs). The hDPSCs were treated with eluates of iRoot FS at
      concentrations of 0.2 and 2 mg/mL, referred to as FS0.2 and FS2, respectively,
      and Biodentine (BD; Septodont, Saint Maur des Fausses, France) eluates at the
      corresponding concentrations as positive controls. A CCK8 assay was performed to
      determine cell proliferation. Wound healing and transwell assays were conducted
      to examine cell migration. Osteogenic differentiation was evaluated based on
      alkaline phosphatase activity, Alizarin Red S staining and quantitative real-time
      reverse-transcriptase polymerase chain reaction (qRT-PCR) to analyze the mRNA
      expression of differentiation gene markers. Cell proliferation was higher in the
      FS and BD groups than in the blank controls at 3 and 7 days. Moreover, FS0.2
      enhanced cell migration and significantly promoted the osteogenic differentiation
      of hDPSCs. These findings suggested that iRoot FS is a bioactive material that
      promotes the proliferation, migration and osteogenic differentiation of hDPSCs.

PMID- 29059237
TI  - Audiovisual communication of object-names improves the spatial accuracy of
      recalled object-locations in topographic maps.
AB  - Knowing the correct location of a specific object learned from a (topographic)
      map is fundamental for orientation and navigation tasks. Spatial reference
      systems, such as coordinates or cardinal directions, are helpful tools for any
      geometric localization of positions that aims to be as exact as possible.
      Considering modern visualization techniques of multimedia cartography, map
      elements transferred through the auditory channel can be added easily.
      Audiovisual approaches have been discussed in the cartographic community for many
      years. However, the effectiveness of audiovisual map elements for map use has
      hardly been explored so far. Within an interdisciplinary (cartography-cognitive
      psychology) research project, it is examined whether map users remember object
      locations better if they do not just read the corresponding place names, but also
      listen to them as voice recordings. This approach is based on the idea that
      learning object-identities influences learning object-locations, which is crucial
      for map-reading tasks. The results of an empirical study show that the additional
      auditory communication of object names not only improves memory for the names
      (object-identities), but also for the spatial accuracy of their corresponding
      object-locations. The audiovisual communication of semantic attribute information
      of a spatial object seems to improve the binding of object-identity and object
      location, which enhances the spatial accuracy of object-location memory.

PMID- 29059238
TI  - Bacillus anthracis lethal toxin negatively modulates ILC3 function through
      perturbation of IL-23-mediated MAPK signaling.
AB  - Bacillus anthracis, the causative agent of anthrax, secretes lethal toxin that
      down-regulates immune functions. Translocation of B. anthracis across mucosal
      epithelia is key for its dissemination and pathogenesis. Group 3 innate
      lymphocytes (ILC3s) are important in mucosal barrier maintenance due to their
      expression of the cytokine IL-22, a critical regulator of tissue responses and
      repair during homeostasis and inflammation. We found that B. anthracis lethal
      toxin perturbed ILC3 function in vitro and in vivo, revealing an unknown IL-23
      mediated MAPK signaling pathway. Lethal toxin had no effects on the canonical
      STAT3-mediated IL-23 signaling pathway. Rather lethal toxin triggered the loss of
      several MAP2K kinases, which correlated with reduced activation of downstream
      ERK1/2 and p38, respectively. Inhibition studies showed the importance of MAPK
      signaling in IL-23-mediated production of IL-22. Our finding that MAPK signaling
      is required for optimal IL-22 production in ILC3s may lead to new approaches for
      targeting IL-22 biology.

PMID- 29059239
TI  - Co-opting ATP-generating glycolytic enzyme PGK1 phosphoglycerate kinase
      facilitates the assembly of viral replicase complexes.
AB  - The intricate interactions between viruses and hosts include exploitation of host
      cells for viral replication by using many cellular resources, metabolites and
      energy. Tomato bushy stunt virus (TBSV), similar to other (+)RNA viruses, induces
      major changes in infected cells that lead to the formation of large replication
      compartments consisting of aggregated peroxisomal and ER membranes. Yet, it is
      not known how TBSV obtains the energy to fuel these energy-consuming processes.
      In the current work, the authors discovered that TBSV co-opts the glycolytic ATP
      generating Pgk1 phosphoglycerate kinase to facilitate the assembly of new viral
      replicase complexes. The recruitment of Pgk1 into the viral replication
      compartment is through direct interaction with the viral replication proteins.
      Altogether, we provide evidence that the ATP generated locally within the
      replication compartment by the co-opted Pgk1 is used to fuel the ATP-requirement
      of the co-opted heat shock protein 70 (Hsp70) chaperone, which is essential for
      the assembly of new viral replicase complexes and the activation of functional
      viral RNA-dependent RNA polymerase. The advantage of direct recruitment of Pgk1
      into the virus replication compartment could be that the virus replicase assembly
      does not need to intensively compete with cellular processes for access to ATP.
      In addition, local production of ATP within the replication compartment could
      greatly facilitate the efficiency of Hsp70-driven replicase assembly by providing
      high ATP concentration within the replication compartment.

PMID- 29059240
TI  - Formation of the chaperonin complex studied by 2D NMR spectroscopy.
AB  - We studied the interaction between GroES and a single-ring mutant (SR1) of GroEL
      by the NMR titration of 15N-labeled GroES with SR1 at three different
      temperatures (20, 25 and 30 degrees C) in the presence of 3 mM ADP in 100 mM KCl
      and 10 mM MgCl2 at pH 7.5. We used SR1 instead of wild-type double-ring GroEL to
      precisely control the stoichiometry of the GroES binding to be 1:1
      ([SR1]:[GroES]). Native heptameric GroES was very flexible, showing well resolved
      cross peaks of the residues in a mobile loop segment (residue 17-34) and at the
      top of a roof hairpin (Asn51) in the heteronuclear single quantum coherence
      spectra. The binding of SR1 to GroES caused the cross peaks to disappear
      simultaneously, and hence it occurred in a single-step cooperative manner with
      significant immobilization of the whole GroES structure. The binding was thus
      entropic with a positive entropy change (219 J/mol/K) and a positive enthalpy
      change (35 kJ/mol), and the binding constant was estimated at 1.9*105 M-1 at 25
      degrees C. The NMR titration in 3 mM ATP also indicated that the binding constant
      between GroES and SR1 increased more than tenfold as compared with the binding
      constant in 3 mM ADP. These results will be discussed in relation to the
      structure and mechanisms of the chaperonin GroEL/GroES complex.

PMID- 29059241
TI  - Highly heterogeneous diazotroph communities in the Kuroshio Current and the
      Tokara Strait, Japan.
AB  - In this study, we used 454-pyrosequencing to report the highly diverse diazotroph
      communities in the Kuroshio and its adjacent waters along a transect across the
      Tokara Strait, Japan. Terrestrial input from the islands resulted in a highly
      heterogeneous diazotroph community within a relatively small geographic region,
      which was presumably caused by the remarkably different responses of UCYN-A2,
      UCYN-C and Trichodesmium to the steep environmental gradient. On the other hand,
      most major cyanobacterial OTUs found in this study were also detected in an
      unpublished dataset from the upstream Kuroshio, which suggests transportation of
      diazotrophs by the Kuroshio in large geographic scale. A significant amount of
      UCYN-C was found in the Kuroshio and offshore stations, suggesting the importance
      of this potentially overlooked group in the western North Pacific Ocean (WNPO).
      Moreover, a novel sublineage of UCYN-B was defined, which was predominant in an
      oligotrophic water sample; and it was also found to be widely distributed in
      oceanic waters. In addition, the apparent increase in relative abundance of UCYN
      A2 from offshore to near-shore water provides evidence for the earlier and under
      debating view that UCYN-A2 prefers coastal conditions. Our report provides new
      knowledge for understanding the phylogeny and ecology of unicellular
      cyanobacterial diazotrophs in WNPO.

PMID- 29059242
TI  - Inhibition of human cytomegalovirus immediate early gene expression and growth by
      a novel RNase P ribozyme variant.
AB  - We have previously engineered new RNase P-based ribozyme variants with improved
      in vitro catalytic activity. In this study, we employed a novel engineered
      variant to target a shared mRNA region of human cytomegalovirus (HCMV) immediate
      early proteins 1 (IE1) and 2 (IE2), which are essential for the expression of
      viral early and late genes as well as viral growth. Ribozyme F-R228-IE represents
      a novel variant that possesses three unique base substitution point mutations at
      the catalytic domain of RNase P catalytic RNA. Compared to F-M1-IE that is the
      ribozyme derived from the wild type RNase P catalytic RNA sequence, the
      functional variant F-R228-IE cleaved the target mRNA sequence in vitro at least
      100 times more efficiently. In cultured cells, expression of F-R228-IE resulted
      in IE1/IE2 expression reduction by 98-99% and in HCMV production reduction by
      50,000 folds. In contrast, expression of F-M1-IE resulted in IE1/IE2 expression
      reduction by less than 80% and in viral production reduction by 200 folds.
      Studies of the ribozyme-mediated antiviral effects in cultured cells suggest that
      overall viral early and late gene expression and viral growth were inhibited due
      to the ribozyme-mediated reduction of HCMV IE1 and IE2 expression. Our results
      provide direct evidence that engineered RNase P ribozymes, such as F-R228-IE, can
      serve as a novel class of inhibitors for the treatment and prevention of HCMV
      infection. Moreover, these results suggest that F-R228-IE, with novel and unique
      mutations at the catalytic domain to enhance ribozyme activity, can be a
      candidate for the construction of effective agents for anti-HCMV therapy.

PMID- 29059243
TI  - Muscle oxygenation in Type 1 diabetic and non-diabetic patients with and without
      chronic compartment syndrome.
AB  - BACKGROUND: Type 1 diabetic patients and non-diabetic patients were referred for
      evaluation for chronic exertional compartment syndrome (CECS) based on clinical
      examination and complaints of activity-related leg pain in the region of the
      tibialis anterior muscle. Previous studies using near-infrared spectroscopy
      (NIRS) showed greater deoxygenation during exercise for CECS patients versus
      healthy controls; however, this comparison has not been done for diabetic CECS
      patients. METHODS: We used NIRS to test for differences in oxygenation kinetics
      for Type 1 diabetic patients diagnosed with (CECS-diabetics, n = 9) versus
      diabetic patients without (CON-diabetics, n = 10) leg anterior chronic exertional
      compartment syndrome. Comparisons were also made between non-diabetic CECS
      patients (n = 11) and healthy controls (CON, n = 10). The experimental protocol
      consisted of thigh arterial cuff occlusion (AO, 1-minute duration), and treadmill
      running to reproduce symptoms. NIRS variables generated were resting StO2%, and
      oxygen recovery following AO. Also, during and following treadmill running the
      magnitude of deoxygenation and oxygen recovery, respectively, were determined.
      RESULTS: There was no difference in resting StO2% between CECS-diabetics (78.2+/
      12.6%) vs. CON-diabetics (69.1+/-20.8%), or between CECS (69.3+/-16.2) vs. CON
      (75.9+/-11.2%). However, oxygen recovery following AO was significantly slower
      for CECS (1.8+/-0.8%/sec) vs. CON (3.8+/-1.7%/sec) (P = 0.002); these data were
      not different between the diabetic groups. StO2% during exercise was lower
      (greater deoxygenation) for CECS-diabetics (6.3+/-8.6%) vs. CON-diabetics (40.4+/
      22.0%), and for CECS (11.3+/-16.8%) vs. CON (34.1+/-21.2%) (P<0.05 for both). The
      rate of oxygen recovery post exercise was faster for CECS-diabetics (3.5+/
      2.6%/sec) vs. CON-diabetics (1.4+/-0.8%/sec) (P = 0.04), and there was a tendency
      of difference for CECS (3.1+/-1.4%/sec) vs. CON (1.9+/-1.3%/sec) (P = 0.05).
      CONCLUSION: The greater deoxygenation during treadmill running for the CECS
      diabetics group (vs. CON-diabetics) is in line with previous studies (and with
      the present study) that compared non-diabetic CECS patients with healthy
      controls. Our findings could suggest that NIRS may be useful as a diagnostic tool
      for assessing Type 1 diabetic patients suspected of CECS.

PMID- 29059244
TI  - Retraction: Functional Characterization of Two Structurally Novel Diacylglycerol
      Acyltransferase2 Isozymes Responsible for the Enhanced Production of Stearate
      Rich Storage Lipid in Candida tropicalis SY005.

PMID- 29059245
TI  - Fungal and bacterial successions in the process of co-composting of organic
      wastes as revealed by 454 pyrosequencing.
AB  - Composting is viewed as one of the primary methods to treat organic wastes. Co
      composting may improve the efficiency of this treatment by establishing the most
      suitable conditions for decomposers than those present in the individual wastes.
      Given that bacteria and fungi are the driving agents of composting, information
      about the composition of their communities and dynamics during composting may
      improve reproducibility, performance and quality of the final compost as well as
      help to evaluate the potential human health risk and the choice of the most
      appropriate application procedure. In this study, the co-composting of mixtures
      containing two similar components (organic fraction of municipal solid waste and
      sawdust polluted by oil) and one discriminate component (sewage sludges of
      different origin) were investigated. Bacterial and fungal community successions
      in the two mixtures were analyzed during the composting process by determining
      the change in their structural dynamics using qPCR and 454 pyrosequencing methods
      in a lab experiment for a period of 270 days. During the initial composting
      stage, the number of 16S bacterial copies was (3.0+/-0.2) x 106 and (0.4+/-0.0) x
      107 g-1, and the Rhodospiralles and Lactobacialles orders dominated. Fungal
      communities had (2.9+/-0.0) x105 and (6.1+/-0.2) x105 ITS copies g-1, and the
      Saccharomycetales order dominated. At the end of the thermophilic stage on the
      30th day of composting, bacterial and fungal communities underwent significant
      changes: dominants changed and their relative abundance decreased. Typical
      compost residents included Flavobacteriales, Chitinophagaceae and Bacterioidetes
      for bacteria and Microascaceae, Dothideomycetes, Eurotiomycetes, Sordariomycetes,
      and Agaricomycetes for fungi. During the later composting stages, the dominating
      taxa of both bacterial and fungal communities remained, while their relative
      abundance decreased. In accordance with the change in the dominating OTUs, it was
      concluded that the dynamics of the bacterial and fungal communities were not
      similar. Analysis by non-metric multidimensional scaling (NMDS) revealed that the
      bacterial communities of the two composts became progressively more similar; a
      similar trend was followed by the fungal community.

PMID- 29059246
TI  - Macavirus latency-associated protein evades immune detection through regulation
      of protein synthesis in cis depending upon its glycin/glutamate-rich domain.
AB  - Alcelaphine herpesvirus 1 (AlHV-1) is a gamma-herpesvirus (gamma-HV) belonging to
      the macavirus genus that persistently infects its natural host, the wildebeest,
      without inducing any clinical sign. However, cross-transmission to other ruminant
      species causes a deadly lymphoproliferative disease named malignant catarrhal
      fever (MCF). AlHV-1 ORF73 encodes the latency-associated nuclear antigen (LANA)
      homolog protein (aLANA). Recently, aLANA has been shown to be essential for viral
      persistence in vivo and induction of MCF, suggesting that aLANA shares key
      properties of other gamma-HV genome maintenance proteins. Here we have
      investigated the evasion of the immune response by aLANA. We found that a
      glycin/glutamate (GE)-rich repeat domain was sufficient to inhibit in cis the
      presentation of an epitope linked to aLANA. Although antigen presentation in
      absence of GE was dependent upon proteasomal degradation of aLANA, a lack of GE
      did not affect protein turnover. However, protein self-synthesis de novo was
      downregulated by aLANA GE, a mechanism directly associated with reduced antigen
      presentation in vitro. Importantly, codon-modification of aLANA GE resulted in
      increased antigen presentation in vitro and enhanced induction of antigen
      specific CD8+ T cell responses in vivo, indicating that mRNA constraints in GE
      rather than peptidic sequence are responsible for cis-limitation of antigen
      presentation. Nonetheless, GE-mediated limitation of antigen presentation in cis
      of aLANA was dispensable during MCF as rabbits developed the disease after virus
      infection irrespective of the expression of full-length or GE-deficient aLANA.
      Altogether, we provide evidence that inhibition in cis of protein synthesis
      through GE is likely involved in long-term immune evasion of AlHV-1 latent
      persistence in the wildebeest natural host, but dispensable in MCF pathogenesis.

PMID- 29059247
TI  - Nutrikinetic study of genistein metabolites in ovariectomized mice.
AB  - This study was designed to evaluate the effect of ovariectomy on nutrikinetics of
      genistein metabolites. To characterize the time-dependent changes in genistein
      metabolite concentrations, we identified 13 genistein metabolites using ultra
      performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
      The nutrikinetics of the individual metabolites at different time points were
      analyzed. Nutrikinetic analysis showed that genistein, genistein 4'-glucuronide,
      genistein 7-glucuronide, 3-hydroxygenistein, and hippuric acid showed relatively
      high bioavailability in the sham group compared to that in the ovariectomy group,
      suggesting that ovariectomy likely results in lower genistein bioavailability.
      These results may be related to alteration of gut microbiota by ovariectomy. The
      relative abundance of species of the Parabacteroides, Dorea, and Butyricimonas
      genera, and Desulfovibrionaceae_unclassified, Lachnospiraceae_unclassified, and
      Rikenellaceae_unclassified families increased in the ovariectomy group while the
      relative abundance of 523_7_unclassified and Y52_unclassified_unclassified
      increased in the sham group. These results suggest that gut microbiota alteration
      by ovariectomy may affect genistein bioavailability.

PMID- 29059248
TI  - Clock-dependent and system-driven oscillators interact in the suprachiasmatic
      nuclei to pace mammalian circadian rhythms.
AB  - Circadian clocks drive biological rhythms with a period of approximately 24 hours
      and keep in time with the outside world through daily resetting by environmental
      cues. While this external entrainment has been extensively investigated in the
      suprachiasmatic nuclei (SCN), the role of internal systemic rhythms, including
      daily fluctuations in core temperature or circulating hormones remains debated.
      Here, we show that lactating mice, which exhibit dampened systemic rhythms,
      possess normal molecular clockwork but impaired rhythms in both heat shock
      response gene expression and electrophysiological output in their SCN. This
      suggests that body rhythms regulate SCN activity downstream of the clock.
      Mathematical modeling predicts that systemic feedback upon the SCN functions as
      an internal oscillator that accounts for in vivo and ex vivo observations. Thus
      we are able to propose a new bottom-up hierarchical organization of circadian
      timekeeping in mammals, based on the interaction in the SCN between clock
      dependent and system-driven oscillators.

PMID- 29059249
TI  - The complex relationship between oligoclonal bands, lymphocytes in the
      cerebrospinal fluid, and immunoglobulin G antibodies in multiple sclerosis:
      Indication of serum contribution.
AB  - INTRODUCTION: Intrathecal immunoglobulin G (IgG) and oligoclonal bands (OCBs) are
      the most consistent and characteristic features of Multiple Sclerosis (MS). OCBs
      in MS are considered products of clonally expanded B cells in the cerebrospinal
      fluid (CSF), representing the sum of contributions from B cells in the brain.
      However, large amounts of IgG can be eluted from MS plaques in which lymphocytes
      are absent, and there is no correlation between levels of plaque-associated IgG
      and the presence of lymphocytes. It is calculated that it would take 3.2 billion
      lymphocytes to generate such large amounts of intrathecal IgG (30 mg in 500 ml
      CSF) in MS patients. Therefore, circulating lymphocytes in CSF could only account
      for <0.1% of the extra IgG in MS. METHODS: We analyzed clinical laboratory
      parameters from sera and CSF of 115 patients including 91 patients with MS and 24
      patients with other inflammatory central nervous system (CNS) disorders (IC). We
      investigated the relationship between oligoclonal bands, IgG antibodies, CSF
      cells, IgG Index, albumin, and total protein. RESULTS: MS patients have
      significantly elevated serum concentrations of IgG antibodies, albumin, and total
      protein, lower levels of lymphocytes, albumin, and total protein in the
      cerebrospinal fluid, but no difference in CSF IgG concentration compared to those
      with other inflammatory neurological disorders. Furthermore, in MS there was no
      linear relationship between the numbers of OCBs, CSF lymphocytes, CSF IgG, and
      IgG Index, and between serum IgG and serum albumin, but significant correlation
      between IgG in CSF and serum, and between CSF IgG and CSF albumin. CONCLUSION:
      There are unique differences between MS and patients with other inflammatory
      neurological disorders. Our data suggest that in MS patient (a) B cells and their
      products in the CSF may not be the sole source of intrathecal IgG; (b)
      oligoclonal bands may not be the products of single B cell clones in the CSF; and
      (c) there is a strong connection between serum components in the peripheral
      circulation and the central nervous system.

PMID- 29059250
TI  - Causative species of nontuberculous mycobacterial lung disease and comparative
      investigation on clinical features of Mycobacterium abscessus complex disease: A
      retrospective analysis for two major hospitals in a subtropical region of Japan.
AB  - Nontuberculous mycobacteria (NTM) lung disease is increasing globally. Although
      the etiological epidemiology of NTM is different across regions, Mycobacterium
      avium complex (MAC) is the leading cause of NTM lung disease in most countries,
      including mainland Japan. Okinawa is located in the southernmost region of Japan
      and is the only prefecture categorized as a subtropical region in Japan, it is
      therefore likely the etiological epidemiology of NTM lung disease is different
      from mainland Japan. From 2009 to 2015, the medical records of patients, with
      respiratory specimens positive for NTMs, visiting or admitted to two Okinawan
      hospitals, were retrospectively analyzed. NTM lung disease cases were defined
      according to the American Thoracic Society criteria and patient epidemiology and
      clinical information were evaluated. Results indicate four hundred sixteen
      patients had bacterial cultures positive for NTM. The most common NTM was M.
      abscessus complex (MABC) (n = 127; 30.5%), followed by M. intracellulare (n = 85;
      20.4%). NTM lung disease was diagnosed in 114 patients. Of these cases, MABC was
      most common (n = 41; 36.0%), followed by M. intracellulare (n = 31; 27.2%).
      Chronic obstructive pulmonary disease (COPD) and tracheostomy patients were more
      likely to develop MABC than MAC lung disease. Multivariate analysis showed a
      probable association between COPD and MABC lung disease. Chest computed
      tomography (CT) evaluation revealed bronchiectasis, nodules, and consolidation
      were less frequently observed in MABC patients compared with MAC patients. Our
      data suggests Okinawa may be one of the few places where MABC is the predominant
      pathogen causing NTM lung disease and our results add new insight to MABC lung
      disease, which is not yet well understood.

PMID- 29059252
TI  - Temperate grassland songbird species accumulate incrementally along a gradient of
      primary productivity.
AB  - Global analyses of bird communities along elevation gradients suggest that bird
      diversity on arid mountains is primarily limited by water availability, not
      temperature or altitude. However, the mechanism by which water availability, and
      subsequently primary productivity, increases bird diversity is still unclear.
      Here we evaluate two possible mechanisms from species-energy theory. The more
      individuals hypothesis proposes that a higher availability of resources increases
      the total number of individuals that can be supported, and therefore the greater
      number of species that will be sampled. By contrast, the more specialization
      hypothesis proposes that increasing resource availability will permit specialists
      to exploit otherwise rare resources, thus increasing total diversity. We used 5
      years of surveys of grassland songbird communities along an elevational gradient
      in British Columbia, Canada, to distinguish between these hypotheses. Vegetation
      changed markedly in composition along the gradient and contrary to the
      expectations of the more specialization hypothesis, bird community composition
      was remarkably constant. However, both total abundance and species richness of
      birds increased with increasing water availability to plants. When we used
      rarefaction to correct species richness for differences in total abundance, much
      of the increase in bird diversity was lost, consistent with the expectations of
      the more individuals hypothesis. Furthermore, high species richness was
      associated with reductions in territory size of common bird species, rather than
      the fine-scale spatial partitioning of the landscape. This suggests that bird
      diversity increases when greater resource availability allows higher densities
      rather than greater habitat specialization. These results help explain a
      pervasive global pattern in bird diversity on arid mountains, and suggest that in
      such landscapes conservation of grassland birds is strongly linked to climate and
      hydrology.

PMID- 29059251
TI  - Advancing the sleep/wake schedule impacts the sleep of African-Americans more
      than European-Americans.
AB  - There are differences in sleep duration between Blacks/African-Americans and
      Whites/European-Americans. Recently, we found differences between these ancestry
      groups in the circadian system, such as circadian period and the magnitude of
      phase shifts. Here we document the role of ancestry on sleep and cognitive
      performance before and after a 9-h advance in the sleep/wake schedule similar to
      flying east or having a large advance in sleep times due to shiftwork, both of
      which produce extreme circadian misalignment. Non-Hispanic African and European
      Americans (N = 20 and 17 respectively, aged 21-43 years) were scheduled to four
      baseline days each with 8 h time in bed based on their habitual sleep schedule.
      This sleep/wake schedule was then advanced 9 h earlier for three days. Sleep was
      monitored using actigraphy. During the last two baseline/aligned days and the
      first two advanced/misaligned days, beginning 2 h after waking, cognitive
      performance was measured every 3 h using the Automated Neuropsychological
      Assessment Metrics (ANAM) test battery. Mixed model ANOVAs assessed the effects
      of ancestry (African-American or European-American) and condition
      (baseline/aligned or advanced/misaligned) on sleep and cognitive performance.
      There was decreased sleep and impaired performance in both ancestry groups during
      the advanced/misaligned days compared to the baseline/aligned days. In addition,
      African-Americans obtained less sleep than European-Americans, especially on the
      first two days of circadian misalignment. Cognitive performance did not differ
      between African-Americans and European-Americans during baseline days. During the
      two advanced/misaligned days, however, African-Americans tended to perform
      slightly worse compared to European-Americans, particularly at times
      corresponding to the end of the baseline sleep episodes. Advancing the sleep/wake
      schedule, creating extreme circadian misalignment, had a greater impact on the
      sleep of African-Americans than European-Americans. Ancestry differences in sleep
      appear to be exacerbated when the sleep/wake schedule is advanced, which may have
      implications for individuals undertaking shiftwork and transmeridian travel.

PMID- 29059253
TI  - A novel electronic algorithm using host biomarker point-of-care tests for the
      management of febrile illnesses in Tanzanian children (e-POCT): A randomized,
      controlled non-inferiority trial.
AB  - BACKGROUND: The management of childhood infections remains inadequate in resource
      limited countries, resulting in high mortality and irrational use of
      antimicrobials. Current disease management tools, such as the Integrated
      Management of Childhood Illness (IMCI) algorithm, rely solely on clinical signs
      and have not made use of available point-of-care tests (POCTs) that can help to
      identify children with severe infections and children in need of antibiotic
      treatment. e-POCT is a novel electronic algorithm based on current evidence; it
      guides clinicians through the entire consultation and recommends treatment based
      on a few clinical signs and POCT results, some performed in all patients (malaria
      rapid diagnostic test, hemoglobin, oximeter) and others in selected subgroups
      only (C-reactive protein, procalcitonin, glucometer). The objective of this trial
      was to determine whether the clinical outcome of febrile children managed by the
      e-POCT tool was non-inferior to that of febrile children managed by a validated
      electronic algorithm derived from IMCI (ALMANACH), while reducing the proportion
      with antibiotic prescription. METHODS AND FINDINGS: We performed a randomized (at
      patient level, blocks of 4), controlled non-inferiority study among children aged
      2-59 months presenting with acute febrile illness to 9 outpatient clinics in Dar
      es Salaam, Tanzania. In parallel, routine care was documented in 2 health
      centers. The primary outcome was the proportion of clinical failures (development
      of severe symptoms, clinical pneumonia on/after day 3, or persistent symptoms at
      day 7) by day 7 of follow-up. Non-inferiority would be declared if the proportion
      of clinical failures with e-POCT was no worse than the proportion of clinical
      failures with ALMANACH, within statistical variability, by a margin of 3%. The
      secondary outcomes included the proportion with antibiotics prescribed on day 0,
      primary referrals, and severe adverse events by day 30 (secondary
      hospitalizations and deaths). We enrolled 3,192 patients between December 2014
      and February 2016 into the randomized study; 3,169 patients (e-POCT: 1,586;
      control [ALMANACH]: 1,583) completed the intervention and day 7 follow-up. Using
      e-POCT, in the per-protocol population, the absolute proportion of clinical
      failures was 2.3% (37/1,586), as compared with 4.1% (65/1,583) in the ALMANACH
      arm (risk difference of clinical failure -1.7, 95% CI -3.0, -0.5), meeting the
      prespecified criterion for non-inferiority. In a non-prespecified superiority
      analysis, we observed a 43% reduction in the relative risk of clinical failure
      when using e-POCT compared to ALMANACH (risk ratio [RR] 0.57, 95% CI 0.38, 0.85,
      p = 0.005). The proportion of severe adverse events was 0.6% in the e-POCT arm
      compared with 1.5% in the ALMANACH arm (RR 0.42, 95% CI 0.20, 0.87, p = 0.02).
      The proportion of antibiotic prescriptions was substantially lower, 11.5%
      compared to 29.7% (RR 0.39, 95% CI 0.33, 0.45, p < 0.001). Using e-POCT, the most
      common indication for antibiotic prescription was severe disease (57%, 103/182
      prescriptions), while it was non-severe respiratory infections using the control
      algorithm (ALMANACH) (70%, 330/470 prescriptions). The proportion of clinical
      failures among the 544 children in the routine care cohort was 4.6% (25/544);
      94.9% (516/544) of patients received antibiotics on day 0, and 1.1% (6/544)
      experienced severe adverse events. e-POCT achieved a 49% reduction in the
      relative risk of clinical failure compared to routine care (RR 0.51, 95% CI 0.31,
      0.84, p = 0.007) and lowered antibiotic prescriptions to 11.5% from 94.9% (p <
      0.001). Though this safety study was an important first step to evaluate e-POCT,
      its true utility should be evaluated through future implementation studies since
      adherence to the algorithm will be an important factor in making use of e-POCT's
      advantages in terms of clinical outcome and antibiotic prescription. CONCLUSIONS:
      e-POCT, an innovative electronic algorithm using host biomarker POCTs, including
      C-reactive protein and procalcitonin, has the potential to improve the clinical
      outcome of children with febrile illnesses while reducing antibiotic use through
      improved identification of children with severe infections, and better targeting
      of children in need of antibiotic prescription. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02225769.

PMID- 29059254
TI  - Anhedonia and anxiety underlying depressive symptomatology have distinct effects
      on reward-based decision-making.
AB  - Depressive pathology, which includes both heightened negative affect (e.g.,
      anxiety) and reduced positive affect (e.g., anhedonia), is known to be associated
      with sub-optimal decision-making, particularly in uncertain environments. Here,
      we use a computational approach to quantify and disambiguate how individual
      differences in these affective measures specifically relate to different aspects
      of learning and decision-making in reward-based choice behavior. Fifty-three
      individuals with a range of depressed mood completed a two-armed bandit task, in
      which they choose between two arms with fixed but unknown reward rates. The
      decision-making component, which chooses among options based on current
      expectations about reward rates, is modeled by two different decision policies: a
      learning-independent Win-stay/Lose-shift (WSLS) policy that ignores all previous
      experiences except the last trial, and Softmax, which prefers the arm with the
      higher expected reward. To model the learning component for the Softmax choice
      policy, we use a Bayesian inference model, which updates estimated reward rates
      based on the observed history of trial outcomes. Softmax with Bayesian learning
      better fits the behavior of 55% of the participants, while the others are better
      fit by a learning-independent WSLS strategy. Among Softmax "users", those with
      higher anhedonia are less likely to choose the option estimated to be most
      rewarding. Moreover, the Softmax parameter mediates the inverse relationship
      between anhedonia and overall monetary gains. On the other hand, among WSLS
      "users", higher state anxiety correlates with increasingly better ability of
      WSLS, relative to Softmax, to explain subjects' trial-by-trial choices. In
      summary, there is significant variability among individuals in their reward
      based, exploratory decision-making, and this variability is at least partly
      mediated in a very specific manner by affective attributes, such as hedonic tone
      and state anxiety.

PMID- 29059255
TI  - Prevalence and predictors of dual antiplatelet therapy prolongation beyond one
      year in patients with acute coronary syndrome.
AB  - There are limited real-world data on prevalence and predictors of dual
      antiplatelet therapy (DAPT) prolongation beyond one year after acute coronary
      syndrome (ACS). We have explored such issue in the START ANTIPLATELET Registry,
      which is a prospective, observational, multicenter, Italian registry performed in
      seven Italian cardiology institutions including patients admitted for ACS and
      followed up to one year. Out of a total population of 840 ACS patients, 596
      patients had completed 12-month follow-up being on DAPT. Decision to prolong DAPT
      beyond one year was taken in 79 patients (13%), whereas in 517 patients DAPT was
      stopped. The strongest predictors of DAPT continuation were a new cardiovascular
      events after the index admission event (OR 3.3, 95% CI 1.4-7.7), no bleeding
      complications (OR 3.2, 95% CI 1.2-8.3) and no anemia during one-year follow-up
      (OR 2.6, 95% CI 1.1-5.9); other independent predictors were renal failure (OR
      2.5, 95% CI 1.3-5.0) and peripheral artery disease (OR 1.8, 95% CI 1.1-3.0). The
      choice of DAPT prolongation was not correlated with younger ager, presence of
      diabetes mellitus, coronary angioplasty as initial treatment strategy or type of
      implanted stent (drug-eluting vs bare metal). In conclusion, this study provides
      a real-world snapshot on the factors influencing the option to continue DAPT
      beyond one year after ACS; a low bleeding risk seems to influence the choice to
      prolong DAPT more than a high ischemic risk.

PMID- 29059256
TI  - Identification of two immortalized cell lines, ECV304 and bEnd3, for in vitro
      permeability studies of blood-brain barrier.
AB  - To identify suitable cell lines for a mimetic system of in vivo blood-brain
      barrier (BBB) for drug permeability assessment, we characterized two immortalized
      cell lines, ECV304 and bEnd3 in the respect of the tightness, tight junction
      proteins, P-glycoprotein (P-gp) function and discriminative brain penetration.
      The ECV304 monoculture achieved higher transendothelial electrical resistance
      (TEER) and lower permeability to Lucifer yellow than bEnd3. However, co-culture
      with rat glioma C6 cells impaired the integrity of ECV304 and bEnd3 cell layers
      perhaps due to the heterogeneity among C6 cells in inducing BBB characteristics.
      The immunostaining of ZO-1 delivered distinct bands along cell borders on both
      cell lines while those of occludin and claudin-5 were diffused and weak. P-gp
      functionality was only proved in bEnd3 by Rhodamine 123 (R123) uptake assay. A
      permeability test of reference compounds displayed a similar rank order (digoxin
      < R123 < quinidine, verapamil < propranolol) in ECV304 and bEnd3 cells. In
      comparison with bEnd3, ECV304 developed tighter barrier for the passage of
      reference compounds and higher discrimination between transcellular and
      paracellular transport. However, the monoculture models of ECV304 and bEnd3 fail
      to achieve the sufficient tightness of in vitro BBB permeability models with high
      TEER and evident immunostaining of tight junction proteins. Further strategies to
      enhance the paracellular tightness of both cell lines to mimic in vivo BBB tight
      barrier deserve to be conducted.

PMID- 29059257
TI  - Fully-automated segmentation of fluid regions in exudative age-related macular
      degeneration subjects: Kernel graph cut in neutrosophic domain.
AB  - A fully-automated method based on graph shortest path, graph cut and neutrosophic
      (NS) sets is presented for fluid segmentation in OCT volumes for exudative age
      related macular degeneration (EAMD) subjects. The proposed method includes three
      main steps: 1) The inner limiting membrane (ILM) and the retinal pigment
      epithelium (RPE) layers are segmented using proposed methods based on graph
      shortest path in NS domain. A flattened RPE boundary is calculated such that all
      three types of fluid regions, intra-retinal, sub-retinal and sub-RPE, are located
      above it. 2) Seed points for fluid (object) and tissue (background) are
      initialized for graph cut by the proposed automated method. 3) A new cost
      function is proposed in kernel space, and is minimized with max-flow/min-cut
      algorithms, leading to a binary segmentation. Important properties of the
      proposed steps are proven and quantitative performance of each step is analyzed
      separately. The proposed method is evaluated using a publicly available dataset
      referred as Optima and a local dataset from the UMN clinic. For fluid
      segmentation in 2D individual slices, the proposed method outperforms the
      previously proposed methods by 18%, 21% with respect to the dice coefficient and
      sensitivity, respectively, on the Optima dataset, and by 16%, 11% and 12% with
      respect to the dice coefficient, sensitivity and precision, respectively, on the
      local UMN dataset. Finally, for 3D fluid volume segmentation, the proposed method
      achieves true positive rate (TPR) and false positive rate (FPR) of 90% and 0.74%,
      respectively, with a correlation of 95% between automated and expert manual
      segmentations using linear regression analysis.

PMID- 29059258
TI  - The Inventory of Depressive Symptomatology Self Report (IDS-SR): Psychometric
      properties of the Indonesian version.
AB  - BACKGROUND: Depression screening and examination in Indonesia are highly
      challenging due to the disproportionately low number of mental health
      professionals in comparison to the Indonesian population. Self-report
      questionnaires on depression are cost-effective and time-efficient. The current
      study investigates the psychometric properties of the Indonesian Inventory of
      Depressive Symptomatology Self Report (IDS-SR). METHODS: The participants were
      904 Indonesians (aged 16-61; 50.2% female), recruited via an online survey using
      Qualtrics. Confirmatory factor analysis of the one-factor, three-factor, and four
      factor model were explored. Convergent and divergent validity of the total score
      of the Indonesian IDS-SR and each factor were examined, as well as the Cronbach's
      Alpha reliability. In addition, an optimal cut-off score for the Indonesian IDS
      SR was established using ROC curve analysis. RESULTS: The three-factor model of
      "cognitive/mood", "anxiety/arousal", and "sleep disturbance" was the best fit
      with the Indonesian IDS-SR data. Convergent and divergent validity were good.
      Cronbach's Alpha reliability was excellent for the total score, good for the
      factors "cognitive/mood" and "anxiety/arousal", but insufficient for the factor
      "sleep disturbance". The optimal cut-off score of the Indonesian IDS-SR was 14,
      with 87% sensitivity and 86% specificity. CONCLUSIONS: As a multifactorial
      instrument to measure depression that has good validity and reliability, the
      Indonesian IDS-SR can be used to assess depressive symptoms for the purpose of
      research and clinical practice. The optimal cut-off score of the Indonesian IDS
      SR is in accordance with the internationally used cut-off score.

PMID- 29059260
TI  - Motivating Health Behaviors in Adolescents Through Behavioral Economics.

PMID- 29059259
TI  - Sclerostin and bone metabolism markers in hyperthyroidism before treatment and
      interrelations between them.
AB  - Sclerostin, which is a glycoprotein produced by osteocytes, reduces the formation
      of bones by inhibiting the Wnt signal pathway. Thyroid hormones are related with
      Wnt signal pathway and it has been reported that increased thyroid hormones in
      hyperthyroidism fasten epiphysis maturation in childhood, and increase the risk
      of bone fractures by stimulating the bone loss in adults. The aim of this study
      was to examine the sclerostin serum levels, the relation between sclerostin and
      thyroid hormones as well as the biochemical markers of the bone metabolism in
      patients with hyperthyroidism (including multinodular goiter and Graves'
      disease), whose treatments have not started yet. No difference was found in the
      serum sclerostin levels between the hyperthyroidism group (n=24) and the control
      group (n=24) (p=0.452). The serum osteocalcin levels and 24-hour urinary
      phosphorus excretion were found to be higher in the hyperthyroid group than in
      the control group (p<0.001, p=0.009). A positive correlation was determined
      between the sclerostin and bone alkaline phosphatase levels (p<0.001); a negative
      correlation between the osteocalcin and thyroid stimulating hormone (TSH)
      (p<0.05); a positive correlation between the osteocalcin and thyroid hormones
      (FT3,FT4) (p<0.001); and a positive correlation between the deoxypyridinoline and
      hydroxyproline (p<0.001). No correlation was determined between sclerostin and
      TSH,FT3,FT4 (p>0.05). Therefore, we consider that a long-term study that covers
      the pre-post treatment stages of hyperthyroidism, including both the destruction
      and construction of the skeleton would be more enlightening. Moreover, the
      assessment of the synthesis of sclerostin in the bone tissue and in the serum
      level might show differences.

PMID- 29059261
TI  - Associations of Electronic Cigarette Nicotine Concentration With Subsequent
      Cigarette Smoking and Vaping Levels in Adolescents.
AB  - Importance: Research indicates that electronic cigarette (e-cigarette) use
      (vaping) among adolescents is associated with the initiation and progression of
      combustible cigarette smoking. The reasons for this association are unknown.
      Objective: To evaluate whether use of e-cigarettes with higher nicotine
      concentrations is associated with subsequent increases in the frequency and
      intensity of combustible cigarette smoking and vaping. Design, Setting, and
      Participants: In this prospective cohort study involving students from 10 high
      schools in the Los Angeles, California, metropolitan area, surveys were
      administered during 10th grade in the spring (baseline) and 11th grade in the
      fall (6-month follow-up) of 2015 to students who reported using e-cigarettes
      within the past 30 days and the nicotine concentration level they used at
      baseline. Exposures: Self-report of baseline e-cigarette nicotine concentration
      of none (0 mg/mL), low (1-5 mg/mL), medium (6-17 mg/mL), or high (>=18 mg/mL)
      typically used during the past 30 days. Main Outcomes and Measures: Frequency of
      combustible cigarette smoking and e-cigarette use within the past 30 days (0 days
      [none], 1-2 days [infrequent], or >=3 days [frequent]) and daily intensity of
      smoking and vaping (number of cigarettes smoked per day, number of vaping
      episodes per day, and number of puffs per vaping episode) at the 6-month follow
      up. Results: The analytic sample included 181 students (96 boys [53.0%] and 85
      girls [47.0%]; mean [SD] age, 16.1 [0.4] years). Each successive increase in
      nicotine concentration (none to low, low to medium, and medium to high) vaped was
      associated with a 2.26 (95% CI, 1.28-3.98) increase in the odds of frequent (vs
      no) smoking and a 1.65 (95% CI, 1.09-2.51) increase in the odds of frequent (vs
      no) vaping at follow-up after adjustment for baseline frequency of smoking and
      vaping and other relevant covariates. Use of e-cigarettes with high (vs no)
      nicotine concentration was associated with a greater number of cigarettes smoked
      per day at follow-up (adjusted rate ratio [RR], 7.03; 95% CI, 6.11-7.95). An
      association with a significantly greater number of vaping episodes per day was
      found with use of low (adjusted RR, 3.32; 95% CI, 2.61-4.03), medium (adjusted
      RR, 3.32; 95% CI, 2.54-4.10), and high (adjusted RR, 2.44; 95% CI, 1.63-3.24)
      nicotine concentrations (vs no nicotine) at baseline. Similar results were found
      for the number of puffs per vaping episode for low (adjusted RR, 2.05; 95% CI,
      1.41-2.70), medium (adjusted RR, 3.39; 95% CI, 2.66-4.11), and high (adjusted RR,
      2.23; 95% CI, 1.42-3.03) nicotine concentrations. Conclusions and Relevance: The
      results of this study provide preliminary evidence that use of e-cigarettes with
      higher nicotine concentrations by youths may increase subsequent frequency and
      intensity of smoking and vaping.

PMID- 29059262
TI  - Quantifying Microvascular Abnormalities With Increasing Severity of Diabetic
      Retinopathy Using Optical Coherence Tomography Angiography.
AB  - Purpose: We quantified retinal and choriocapillaris microvascular changes in
      healthy control eyes and different stages of diabetic retinopathy (DR) using
      optical coherence tomography angiography (OCTA). Methods: This retrospective
      cross-sectional study included 137 eyes of 86 patients with different stages of
      DR and 44 eyes of 26 healthy age-matched controls. Participants were imaged with
      a commercial OCTA device (RTVue-XR Avanti). We analyzed the superficial (SCP) and
      deep (DCP) retinal capillary plexus, the full retina, and choriocapillaris for
      the following OCTA parameters: foveal avascular zone, vessel density, percent
      area of nonperfusion (PAN), and adjusted flow index (AFI). We adjusted for age,
      sex, and the correlation between eyes of the same study participant in our
      statistical models. Results: All OCTA parameters showed a significant linear
      correlation with DR severity (P < 0.05) in the univariate models except for AFI
      measured in the SCP and these correlations remained significant after correcting
      for covariates. Compared to the other capillary layers, the AFI at the DCP
      decreased significantly with DR severity. When comparing individual disease
      severity groups as categories, eyes of subjects with diabetes without DR had
      significantly increased PAN and AFI in the SCP compared to healthy subjects (P <
      0.05). Conclusions: Retinal and choriocapillaris vascular nonperfusion in OCTA is
      correlated significantly with disease severity in eyes with DR. Higher flow in
      the SCP may be an early marker of diabetic microvascular changes before clinical
      signs of DR. The steep decline of blood flow in the DCP with increasing DR
      severity suggests that alterations at the DCP warrant further investigation.

PMID- 29059264
TI  - Challenges in Communicating and Understanding Predictive Biomarker Imaging for
      Alzheimer Disease.

PMID- 29059263
TI  - Effect of Financial Incentives on Glucose Monitoring Adherence and Glycemic
      Control Among Adolescents and Young Adults With Type 1 Diabetes: A Randomized
      Clinical Trial.
AB  - Importance: Glycemic control often deteriorates during adolescence and the
      transition to young adulthood for patients with type 1 diabetes. The inability to
      manage type 1 diabetes effectively during these years is associated with poor
      glycemic control and complications from diabetes in adult life. Objective: To
      determine the effect of daily financial incentives on glucose monitoring
      adherence and glycemic control in adolescents and young adults with type 1
      diabetes. Design, Setting, and Participants: The Behavioral Economic Incentives
      to Improve Glycemic Control Among Adolescents and Young Adults With Type 1
      Diabetes (BE IN CONTROL) study was an investigator-blinded, 6-month, 2-arm
      randomized clinical trial conducted between January 22 and November 2, 2016, with
      3-month intervention and follow-up periods. Ninety participants (aged 14-20) with
      suboptimally controlled type 1 diabetes (hemoglobin A1c [HbA1c] >8.0%) were
      recruited from the Diabetes Center for Children at the Children's Hospital of
      Philadelphia. Interventions: All participants were given daily blood glucose
      monitoring goals of 4 or more checks per day with 1 or more level within the goal
      range (70-180 mg/dL) collected with a wireless glucometer. The 3-month
      intervention consisted of a $60 monthly incentive in a virtual account, from
      which $2 was subtracted for every day of nonadherence to the monitoring goals.
      During a 3-month follow-up period, the intervention was discontinued. Main
      Outcomes and Measures: The primary outcome was change in HbA1c levels at 3
      months. Secondary outcomes included adherence to glucose monitoring and change in
      HbA1c levels at 6 months. All analyses were by intention to treat. Results: Of
      the 181 participants screened, 90 (52 [57.8%] girls) were randomized to the
      intervention (n = 45) or control (n = 45) arms. The mean (SD) age was 16.3 (1.9)
      years. The intervention group had significantly greater adherence to glucose
      monitoring goals in the incentive period (50.0% vs 18.9%; adjusted difference,
      27.2%; 95% CI, 9.5% to 45.0%; P = .003) but not in the follow-up period (15.3% vs
      8.7%; adjusted difference, 3.9%; 95% CI, -2.0% to 9.9%; P = .20). The change in
      HbA1c levels from baseline did not differ significantly between groups at 3
      months (adjusted difference, -0.08%; 95% CI, -0.69% to 0.54%; P = .80) or 6
      months (adjusted difference, 0.03%; 95% CI, -0.55% to 0.60%; P = .93).
      Conclusions and Relevance: Among adolescents and young adults with type 1
      diabetes, daily financial incentives improved glucose monitoring adherence during
      the incentive period but did not significantly improve glycemic control. Trial
      Registration: clinicaltrials.gov Identifier: NCT02568501.

PMID- 29059265
TI  - What Parents Need to Know About Electronic Cigarettes.

PMID- 29059267
TI  - A Clear Speech Approach to Accent Management.
AB  - Purpose: A 5-session twice-weekly clear speech protocol with daily home practice
      was developed to enable Spanish-accented speakers of English to code-switch for
      increased listener ease of understanding. This study provides preliminary data to
      test the hypothesis that this protocol results in increased ease of understanding
      for native English listeners, not in decreased talker accentedness. Method: Using
      a single-case experimental design, 6 adult native Spanish speakers with English
      proficiency participated in the protocol. Ease of understanding and accentedness
      were probed at least 5 times pretraining, at each training session, and once per
      week for 5 weeks posttraining. Thirty native English-speaking listeners assessed
      the probes using 7-point scales for each measure. Results: Ease of understanding
      improved for all participants (mean improvement = 3.5 points; effect size range =
      6.98 to 15.33). Accentedness improved for 4 of 6 participants (mean improvement =
      2.3 points; effect size range = 4.04 to 10.48). At the outset, most participants
      expressed concern that this approach would highlight speech errors. Upon follow
      up, all participants reported confidence in using the approach and found it
      helpful in daily communication. Conclusions: Further research should explore the
      effects of this protocol on intelligibility and acoustic metrics and their
      relationship to ease of understanding and accentedness.

PMID- 29059268
TI  - Evaluation of a Reflex Testing Algorithm for Suspected Heparin-Induced
      Thrombocytopenia.
AB  - Objectives: We implemented a policy of reflex serotonin-release assay (SRA)
      testing for all patients with a positive heparin-induced thrombocytopenia (HIT)
      immunoassay. Methods: We identified all patients who had SRA testing sent as a
      consequence of a positive HIT immunoassay test. We reviewed charts of patients to
      calculate the 4Ts clinical score, determined the effect of testing on clinical
      management, and documented the change in utilization of direct thrombin
      inhibitors (DTIs). Results: The likelihood of a positive SRA varied with the
      optical density (OD) of the immunoassay. The performance of the immunoglobulin G
      (IgG)-specific and polytypic enzyme-linked immunosorbent assay was not
      statistically different. Both OD and 4Ts score correlated with the likelihood of
      a positive SRA but demonstrated poor specificity. Discontinuation of DTIs in
      patients with negative SRAs resulted in decreased drug utilization. Conclusions:
      The IgG-specific HIT immunoassay OD correlates with the likelihood of a positive
      SRA but does not achieve high specificity. The reflex testing algorithm allows
      for definitive classification of patients, and the cost of such a reflex testing
      program may be offset by decreased utilization of DTIs.

PMID- 29059266
TI  - Disability Trajectories Before and After Stroke and Myocardial Infarction: The
      Cardiovascular Health Study.
AB  - Importance: Ischemic strokes may accelerate long-term functional decline apart
      from their acute effects on neurologic function. Objective: To test whether the
      increase in long-term disability is steeper after than before the event for
      ischemic stroke but not myocardial infarction (MI). Design, Settings, and
      Participants: In the population-based, prospective cohort Cardiovascular Health
      Study (1989-2013), longitudinal follow-up was conducted for a mean (SD) of 13
      (6.2) years. Follow-up data were used until September 1, 2013; data analysis was
      performed from August 1, 2013, to June 1, 2016. Models based on generalized
      estimating equations adjusted for baseline covariates and included a test for
      different slopes of disability before and after the event. Participants included
      5888 Medicare-eligible individuals 65 years or older who were not
      institutionalized, expected to reside in the area for 3 or more years, and able
      to provide informed consent. Exclusions were needing a wheelchair, receiving
      hospice care, and undergoing radiotherapy or chemotherapy. Exposures: Ischemic
      stroke and MI. Main Outcomes and Measures: Annual assessments with a disability
      scale (measuring activities of daily living [ADLs] and instrumental ADLs). The
      number of ADLs and instrumental ADLs (range, 0-12) that the participant could not
      perform was analyzed continuously. Results: The mean (SD) age of the entire
      cohort (n = 5888) was 72.8 (5.6) years; 2495 (42.4%) were male. During follow-up,
      382 (6.5%) participants had ischemic stroke and 395 (6.7%) had MI with 1 or more
      disability assessment after the event. There was a mean of 3.7 (2.4) visits
      before stroke and 3.7 (2.3) visits after stroke; there was a mean of 3.8 (2.5)
      visits before MI and 3.8 (2.4) visits after MI. The increase in disability near
      the time of the event was greater for stroke (0.88 points on the disability
      scale; 95% CI, 0.57 to 1.20; P < .001) than MI (0.20 points on the disability
      scale; 95% CI, 0.06 to 0.35; P = .006). The annual increase in disability before
      stroke (0.06 points per year; 95% CI, 0.002 to 0.12; P = .04) more than tripled
      after stroke (0.15 additional points per year; 95% CI, 0.004 to 0.30; P = .04).
      The annual increase in disability before MI (0.04 points per year; 95% CI, 0.004
      to 0.08; P = .03) did not change significantly after MI (0.02 additional points
      per year; 95% CI, -0.07 to 0.11; P = .69). Conclusions and Relevance: In this
      large, population-based study, a trajectory of increasing disability became
      significantly steeper after stroke but not after MI. Thus, in addition to the
      acute brain injury and consequent impairment, ischemic stroke may also be
      associated with potentially treatable long-term adverse effects on the brain that
      lead to accelerated functional decline.

PMID- 29059269
TI  - The Practice and Implications of Finding Fluid During Point-of-Care
      Ultrasonography: A Review.
AB  - Importance: Point-of-care ultrasonography (POCUS) is an increasingly affordable
      and portable technology that is an important part of 21st-century medicine. When
      appropriately used, POCUS has the potential to expedite diagnosis and improve
      procedural success and safety. POCUS is now being adopted in medical education as
      early as the first year of medical school. While potentially powerful and
      versatile, POCUS is a user-dependent technology that has not been formalized or
      standardized yet within internal medicine residency training programs. Physicians
      and residency directors are trying to determine whether to incorporate POCUS, and
      if so, how. In this systematic review, basic concepts and applications of POCUS
      are examined, as are issues surrounding training and implementation.
      Observations: A key use of POCUS is to detect fluid, and this is a cornerstone of
      POCUS teaching. Even in inexperienced hands, POCUS has shown to be more sensitive
      and specific than physical examination for conditions such as ascites, pleural
      effusion, and pericardial effusion. Detecting fluid requires a basic
      understanding of ultrasonography operation, sonographic anatomy, and probe
      orientation. Once fluid is localized, ultrasonographic guidance can increase
      success and decrease complications of common procedures such as thoracentesis or
      paracentesis. Conclusions and Relevance: POCUS can augment physical examination
      and procedural efficacy but requires appropriate education and program setup. As
      POCUS continues to spread, internal medicine physicians need to clarify how they
      intend to use this technology. Equipment is now increasingly accessible, but
      programs need to determine how to allocate time and resources to training,
      clinical use, and quality assurance. Programs that develop robust implementation
      processes that establish proper scope of practice and include quality assurance
      that use image archival and feedback can ensure POCUS will positively impact
      patient care across hospital systems.

PMID- 29059270
TI  - Comprehension of an Elevated Amyloid Positron Emission Tomography Biomarker
      Result by Cognitively Normal Older Adults.
AB  - Importance: The goal of Alzheimer disease (AD) prevention together with advances
      in understanding the pathophysiology of AD have led to clinical trials testing
      drugs in cognitively unimpaired persons who show evidence of AD biomarkers. Data
      are needed to inform the processes of describing AD biomarkers to cognitively
      normal adults and assessing their understanding of this knowledge. Objective: To
      determine the comprehension of an elevated amyloid positron emission tomographic
      (PET) biomarker result by cognitively unimpaired adults. Design, Setting, and
      Participants: The Study of Knowledge and Reactions to Amyloid Testing, a substudy
      of an AD prevention trial, involved 2 semistructured telephone interviews with 80
      participants recruited from 9 study sites: 50 received elevated and 30 received
      not elevated amyloid PET scan results. Interviews were conducted 4 to 12 weeks
      after result disclosure and again 1 year later. Data presented here were
      collected from November 5, 2014, through December 10, 2015. The 50 participants
      included in this study were cognitively normal, aged 65 to 85 years, evenly
      distributed by gender, and had elevated amyloid PET results. Subsequent reports
      will examine persons with "not elevated" results and compare the influence of the
      different results. Main Outcomes and Measures: Participant comprehension of an
      elevated amyloid result was assessed by analyzing their responses to the
      following questions: "What was the result of your amyloid PET scan?" (followed by
      "Can you tell me in your own words what that means?" or "How would you explain it
      to a friend?"), "Was it the result you expected?" and "Did the result teach you
      anything or clarify anything for you?" Results: Of the 50 participants aged 65 to
      85 years, 49 (98%) were white, 40 (80%) reported a family history of AD, and 30
      (60%) had a postgraduate educational level. Most participants (31 [62%])
      understood that elevated amyloid conferred an increased but uncertain risk of
      developing AD. Some desired understanding of the term elevated other than its
      being a categorical result enabling trial entry eligibility; they wanted
      information regarding how elevated their amyloid was, how close to the study
      threshold they were, or percentages, numbers, or a scale to help them make sense
      of the result. Conclusions and Relevance: Including an explanation of how and why
      a dimensional biomarker is converted to a categorical classification would
      enhance future AD biomarker clinical trials and educational materials.

PMID- 29059271
TI  - The Value of Preterm Infant Environmental Health Cohorts: The Canary in the Coal
      Mine.

PMID- 29059272
TI  - Erratum: "Reporting the Fatigue Life of 316L Stainless Steel Locking Compression
      Plate Implants: The Role of the Femoral and Tibial Biomechanics During the Gait"
      [ASME J. Biomech. Eng., 2017, 139(10), p. 104502; DOI: 10.1115/1.4037561].

PMID- 29059274
TI  - Music and Medicine: Something Important.

PMID- 29059275
TI  - Health and Wealth in the United States and England-Two Very Different Countries
      With Similar Findings.

PMID- 29059273
TI  - A randomized, double-blind, placebo-controlled phase II study of maintenance
      therapy with tasquinimod in patients with metastatic castration-resistant
      prostate cancer responsive to or stabilized during first-line docetaxel
      chemotherapy.
AB  - Background: This phase II study was conducted to assess clinical efficacy of
      tasquinimod maintenance therapy in patients with metastatic castrate-resistant
      prostate cancer not progressing during first-line docetaxel-based therapy.
      Patients and methods: Patients were randomly assigned (1 : 1) to receive
      tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was
      radiologic progression-free survival (rPFS); secondary efficacy end points
      included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic
      PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic
      use. Quality of life was measured by the Functional Assessment of Cancer Therapy
      Prostate (FACT-P) questionnaire and by the EuroQol-5 Dimension Quality of Life
      Instrument (EQ-5D). Adverse events were recorded. Results: A total of 219
      patients were screened and 144 patients randomized. The median duration of
      treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2
      weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7
      (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms,
      respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0.0162]. The median OS was not
      reached because only 14 deaths occurred by the cut-off date. No statistically
      significant differences between treatment arms were noted for symptomatic PFS,
      PFS 2, BPI score, FACT-P score, or EQ-5D. The incidence of any treatment emergent
      adverse event (TEAE) was similar in the tasquinimod and placebo arms (97.2%
      versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence
      was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized
      trials testing new drugs as maintenance can be successfully conducted after
      chemotherapy in castrate-resistant prostate cancer. Maintenance tasquinimod
      therapy significantly reduced the risk of rPFS by 40%. ClinicalTrials: gov
      identifier NCT01732549.

PMID- 29059276
TI  - Treating the "Wake-up Call" of Alcohol Use: A Teachable Moment.

PMID- 29059278
TI  - Data Error, Missing Sentence, and Misnumbered References.

PMID- 29059277
TI  - Intervention With Brief Cessation Advice Plus Active Referral for Proactively
      Recruited Community Smokers: A Pragmatic Cluster Randomized Clinical Trial.
AB  - Importance: Most smoking cessation (SC) clinics are costly, passive, and
      underused. Objective: To compare the SC effect of a combined intervention
      involving brief, model-guided SC advice plus active referral to SC services
      (active referral group) with those of brief, model-guided SC advice only (brief
      advice group) and general SC advice only (control group). Design, Setting, and
      Participants: A single-blind, 3-arm, pragmatic cluster randomized clinical trial
      was conducted including 1226 adult daily smokers in the general Hong Kong
      community proactively recruited to participate in the Quit-to-Win Contest held in
      2015. The study was conducted from June 20 to September 24, 2015. Participants
      were randomly allocated to the active referral (n = 402), brief advice (n = 416),
      and control (n = 408) groups. Intention-to-treat analysis was used.
      Interventions: Brief telephone counseling was offered to the active referral and
      brief advice groups at 1 and 2 months. Interventions were delivered by SC
      ambassadors who had undergone a short training period. Main Outcomes and
      Measures: The primary outcome was the self-reported past 7-day point prevalence
      of abstinence (PPA) at 6 months. The secondary outcomes were carbon monoxide
      level-validated abstinence, smoking reduction, and SC service use. Results:
      Participants included 991 (80.8%) men; mean (SD) age was 42.0 (14.8) years. The
      response rate was 68.2% at 3 and 72.3% at 6 months. The corresponding PPAs were
      18.9% and 17.2% in the active referral group-higher than in the brief advice
      (8.9% and 9.4%; both P <= .001) or control (14.0% and 11.5%; P = .03 at 6 months)
      groups. Compared with the other 2 groups, the active referral group had
      significantly higher validated abstinence rates (10.2% at 3 months and 9.0% at 6
      months, all P < .05) with odds ratios of 2.84 (95% CI, 1.57-5.15) and 2.61 (95%
      CI, 1.46-4.68) at 3 months, and 1.85 (95% CI, 1.06-3.23) and 1.81 (95% CI, 1.04
      3.16) at 6 months in the brief advice and control groups, respectively. The SC
      service use rate was significantly higher in the active referral group (25.1%)
      than in either brief advice (2.4%) or control (3.4%) groups at 6 months (P <
      .001). Conclusions and Relevance: An intervention involving brief advice and
      active referral delivered to smokers in the community by volunteers can increase
      quitting in places where SC services are available but underused. Trial
      Registration: clinicaltrials.gov Identifier: NCT02539875.

PMID- 29059279
TI  - Wealth-Associated Disparities in Death and Disability in the United States and
      England.
AB  - Importance: Low income has been associated with poor health outcomes. Owing to
      retirement, wealth may be a better marker of financial resources among older
      adults. Objective: To determine the association of wealth with mortality and
      disability among older adults in the United States and England. Design, Setting,
      and Participants: The US Health and Retirement Study (HRS) and English
      Longitudinal Study of Aging (ELSA) are nationally representative cohorts of
      community-dwelling older adults. We examined 12 173 participants enrolled in HRS
      and 7599 enrolled in ELSA in 2002. Analyses were stratified by age (54-64 years
      vs 66-76 years) because many safety-net programs commence around age 65 years.
      Participants were followed until 2012 for mortality and disability. Exposures:
      Wealth quintile, based on total net worth in 2002. Main Outcomes and Measures:
      Mortality and disability, defined as difficulty performing an activity of daily
      living. Results: A total of 6233 US respondents and 4325 English respondents aged
      54 to 64 years (younger cohort) and 5940 US respondents and 3274 English
      respondents aged 66 to 76 years (older cohort) were analyzed for the mortality
      outcome. Slightly over half of respondents were women (HRS: 6570, 54%; ELSA:
      3974, 52%). A higher proportion of respondents from HRS were nonwhite compared
      with ELSA in both the younger (14% vs 3%) and the older (13% vs 3%) age cohorts.
      We found increased risk of death and disability as wealth decreased. In the
      United States, participants aged 54 to 64 years in the lowest wealth quintile
      (Q1) (<=$39 000) had a 17% mortality risk and 48% disability risk over 10 years,
      whereas in the highest wealth quintile (Q5) (>$560 000) participants had a 5%
      mortality risk and 15% disability risk (mortality hazard ratio [HR], 3.3; 95% CI,
      2.0-5.6; P < .001; disability subhazard ratio [sHR], 4.0; 95% CI, 2.9-5.6; P <
      .001). In England, participants aged 54 to 64 years in Q1 (<=L34,000) had a 16%
      mortality risk and 42% disability risk over 10 years, whereas Q5 participants
      (>L310,550) had a 4% mortality risk and 17% disability risk (mortality HR, 4.4;
      95% CI, 2.7-7.0; P < .001; disability sHR, 3.0; 95% CI, 2.1-4.2; P < .001). In 66
      to 76-year-old participants, the absolute risks of mortality and disability were
      higher, but risk gradients across wealth quintiles were similar. When adjusted
      for sex, age, race, income, and education, HR for mortality and sHR for
      disability were attenuated but remained statistically significant. Conclusions
      and Relevance: Low wealth was associated with death and disability in both the
      United States and England. This relationship was apparent from age 54 years and
      continued into later life. Access to health care may not attenuate wealth
      associated disparities in older adults.

PMID- 29059280
TI  - Using Spatial and Temporal Mapping to Identify Nosocomial Disease Transmission of
      Clostridium difficile.

PMID- 29059281
TI  - The Evolution of Procedural Competency in Internal Medicine Training.

PMID- 29059282
TI  - Gorenek B, et al. Device-detected subclinical atrial tachyarrhythmias:
      definition, implications and management-an European Heart Rhythm Association
      (EHRA) consensus document, endorsed by Heart Rhythm Society (HRS), Asia Pacific
      Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulacion
      Cardiaca y Electrofisiologia (SOLEACE).

PMID- 29059283
TI  - iSmaRT: a toolkit for a comprehensive analysis of small RNA-Seq data.

PMID- 29059284
TI  - CaMKII blockade, cardiac conduction, and arrhythmia.

PMID- 29059285
TI  - Computational tools for plant small RNA detection and categorization.
AB  - Small RNAs (sRNAs) are important short-length molecules with regulatory functions
      essential for plant development and plasticity. High-throughput sequencing of
      total sRNA populations has revealed that the largest share of sRNA remains
      uncategorized. To better understand the role of sRNA-mediated cellular
      regulation, it is necessary to create accurate and comprehensive catalogues of
      sRNA and their sequence features, a task that currently relies on nontrivial
      bioinformatic approaches. Although a large number of computational tools have
      been developed to predict features of sRNA sequences, these tools are mostly
      dedicated to microRNAs and none integrates the functionalities necessary to
      describe units from all sRNA pathways thus far discovered in plants. Here, we
      review the different classes of sRNA found in plants and describe available
      bioinformatics tools that can help in their detection and categorization.

PMID- 29059286
TI  - Advantages of sacubitril/valsartan beyond blood pressure control in arterial
      hypertension.

PMID- 29059287
TI  - Early anterior crossbite correction through posterior bite opening: a 3D
      superimposition prospective cohort study.
AB  - Objectives: To assess the effectiveness, clinical performance, and potential
      adverse effects of early anterior crossbite correction through opening of the
      bite. Subjects and methods: The sample consisted of 16 consecutive patients (8.0
      +/- 0.9, range: 6.2-9.3 years) with dental anterior crossbite in the mixed
      dentition who were treated through posterior bite opening. Patients were
      prospectively followed until a minimum of 6 months post-treatment and there were
      no drop-outs. Results: In 14 patients (87.5 per cent), the anterior crossbite was
      corrected. Results remained stable without any retention regime. Active treatment
      of the successfully treated cases lasted 2.5 months (range: 0.6-8.9). Crossbite
      correction of central incisors was achieved by a 2.05 mm (range: 0.97-5.45)
      forward movement and 9.25 degrees  (range: 2.32-14.52 degrees ) buccal
      inclination of the crowns (P < 0.05). The antagonists showed spontaneous
      adaptation of their position in the opposite direction (P < 0.05). No important
      adverse effects were recorded. Limitations: This was a non-comparative controlled
      study, on a limited sample. Conclusions: Bite opening is a promising, simple, and
      non-compliance approach for early dental anterior crossbite correction. The
      technique of 3D superimposition and analysis of digital models used here, allowed
      precise evaluation of single tooth movement in all three planes of space.

PMID- 29059289
TI  - Bonded versus vacuum-formed retainers: a randomized controlled trial. Part 1:
      stability, retainer survival, and patient satisfaction outcomes after 12 months.
AB  - Background: There is a shortage of evidence on the best type of retainer.
      Objectives: Evaluate upper and lower bonded retainers (BRs) versus upper and
      lower vacuum-formed retainers (VFRs) over 12 months, in terms of stability,
      retainer survival, and patient satisfaction. Trial design: Two-arm parallel group
      multi-centre randomized controlled clinical trial. Methods: Sixty consecutive
      patients completing fixed appliance therapy and requiring retainers were
      recruited from 3 hospital departments. They were randomly allocated to either
      upper and lower labial segment BRs (n = 30) or upper and lower full-arch VFRs (n
      = 30). Primary outcome was stability. Secondary outcomes were retainer survival
      and patient satisfaction. A random sequence of treatment allocation was computer
      generated and implemented by sealing in sequentially numbered opaque sealed
      envelopes independently prepared in advance. Patients, operators and outcome
      could not be blinded due to the nature of the intervention. Results: Thirty
      patients received BRs (median [Mdn] age 16 years, inter-quartile range [IQR] = 2)
      and 30 received VFRs (Mdn age 17 years, IQR = 4). Baseline characteristics were
      similar between groups. At 12 months, there were no statistically significant
      inter-group differences in post-treatment change of maxillary labial segment
      alignment (BR = 1.1 mm, IQR = 1.56, VFR = 0.76 mm, IQR = 1.55, P = 0.61);
      however, there was greater post-treatment change in the mandibular VFR group (BR
      = 0.77 mm, IQR = 1.46, VFR = 1.69mm, IQR = 2.00, P = 0.008). The difference in
      maxillary retainer survival rates were statistically non-significant, P = 0.34
      (BR = 63.6%, 239.3 days, 95% confidence interval [CI] = 191.1-287.5, VFR = 73.3%,
      311.1 days, 95% CI = 278.3-344.29). The mandibular BR had a lower survival rate
      (P = 0.01) at 12 months (BR = 50%, 239.3 days 95% CI = 191.1-287.5, VFR = 80%,
      324.9 days 95% CI = 295.4-354.4). More subjects with VFRs reported discomfort (P
      = 0.002) and speech difficulties (P = 0.004) but found them easier to clean than
      those with BRs (P = 0.001). Limitations: Results are after 1 year and we do not
      know how much the removable retainers were worn. Conclusions: After 1 year, there
      is no evidence of a significant difference in stability or retainer survival in
      the maxilla. In the mandible, BRs are more effective at maintaining mandibular
      labial segment alignment, but have a higher failure rate. In comparison with
      patients wearing VFRs, patients wearing BRs reported that they caused less
      interference with speech, required less compliance to wear them, and were more
      comfortable to wear than VFRs. Patients found the BRs harder to keep clean. Trial
      registration: The trail was not registered.

PMID- 29059288
TI  - Neural Encoding and Decoding with Deep Learning for Dynamic Natural Vision.
AB  - Convolutional neural network (CNN) driven by image recognition has been shown to
      be able to explain cortical responses to static pictures at ventral-stream areas.
      Here, we further showed that such CNN could reliably predict and decode
      functional magnetic resonance imaging data from humans watching natural movies,
      despite its lack of any mechanism to account for temporal dynamics or feedback
      processing. Using separate data, encoding and decoding models were developed and
      evaluated for describing the bi-directional relationships between the CNN and the
      brain. Through the encoding models, the CNN-predicted areas covered not only the
      ventral stream, but also the dorsal stream, albeit to a lesser degree; single
      voxel response was visualized as the specific pixel pattern that drove the
      response, revealing the distinct representation of individual cortical location;
      cortical activation was synthesized from natural images with high-throughput to
      map category representation, contrast, and selectivity. Through the decoding
      models, fMRI signals were directly decoded to estimate the feature
      representations in both visual and semantic spaces, for direct visual
      reconstruction and semantic categorization, respectively. These results
      corroborate, generalize, and extend previous findings, and highlight the value of
      using deep learning, as an all-in-one model of the visual cortex, to understand
      and decode natural vision.

PMID- 29059291
TI  - Cardiomyopathy in Friedreich's Ataxia.

PMID- 29059290
TI  - Regeneration of Functional Adrenal Tissue Following Bilateral Adrenalectomy.
AB  - It is assumed that after complete bilateral adrenalectomy (ADX), no adrenal
      tissue will redevelop and adrenal hormone levels will remain low and unaffected
      by stress. However, anecdotal observations in animals and in patients suggest
      that under some unknown circumstances the opposite can occur. Herein, we studied
      whether adrenalectomized rats can develop an alternative source of systemic
      corticosterone after complete bilateral ADX with minimal replacement therapy.
      Male and female rats underwent either a standard ADX, in which the glands were
      removed with minimal surrounding adipose tissue, or an extensive ADX, in which
      glands were removed with most surrounding adipose tissue. Excised glands were
      histologically tested for completeness, and corticosterone replacement was
      nullified within 1 to 3 weeks postoperatively. In four experiments and in both
      excision approaches, some rats gradually reestablished baseline corticosterone
      levels and stress response in a time-dependent manner, but differences were
      observed in the reestablishing rates: 80% in standard ADX vs 20% in extensive
      ADX. Upon searching for the source of corticosterone secretion, we were surprised
      to find functional macroscopic foci of adrenocortical tissue without medullary
      tissue, mostly proximal to the original location. Chronic stress accelerated
      corticosterone level reestablishment. We hypothesized that underlying this
      phenomenon were preexisting ectopic microscopic foci of adrenocortical-like
      tissue or a few adrenal cells that were pre-embedded in surrounding tissue or
      detached from the excised gland upon removal. We concluded that adrenalectomized
      animals may develop compensatory mechanisms and suggest that studies employing
      ADX consider additional corticosterone supplementation, minimize stress, and
      verify the absence of circulating corticosterone.

PMID- 29059292
TI  - Additional value of native T1 mapping in tissue characterization of cardiac
      aspergillosis.

PMID- 29059293
TI  - Bonded versus vacuum-formed retainers: a randomized controlled trial. Part 2:
      periodontal health outcomes after 12 months.
AB  - Background: Retainer have the potential to compromise periodontal health.
      Objectives: Evaluate the periodontal health implications of upper and lower
      bonded retainers (BRs) versus upper and lower vacuum-formed retainers (VFRs) over
      12 months. Trial design: Two-arm parallel group multicentre randomized controlled
      clinical trial. Methods: Sixty consecutive patients completing upper and lower
      fixed appliance therapy and requiring retainers were recruited from three
      hospital orthodontic departments. They were randomly allocated to either upper
      and lower labial segment BRs (n = 30) or upper and lower full-arch VFRs (n = 30).
      Periodontal health was assessed using the plaque and gingival indices of Silness
      and Loe, and the calculus index of Greene and Vermillion. Data were collected at
      debond and placement of the retainers (T0), 3 months (T1), 6 months (T2), and 12
      months (T3). A random sequence of treatment allocation was computer-generated and
      implemented by sealing in sequentially numbered opaque sealed envelopes
      independently prepared in advance. Patients, operators, and outcome could not be
      blinded due to the nature of the intervention. Results: Thirty patients received
      BRs (median age 16 years, interquartile range [IQR] = 2, 50% female, 50% male)
      and 30 received VFRs (median age 17 years, IQR = 4, 60% female, 40% male).
      Gingival inflammation decreased from baseline for both types of retainer. There
      was significantly less plaque and calculus accumulation and better gingival
      health with VFRs than BRs over the evaluated 12 months. No serious harm was
      observed. Limitations: It is not known how much the patients chose to wear their
      removable retainers. The results reported are after 1 year only. Conclusions:
      After 1 year, BRs were associated with greater accumulation of plaque and
      calculus than VFRs and minimally worse gingival inflammation than VFRs, but this
      did not appear to produce any clinically significant, adverse periodontal health
      problems. Trial registration: This trial was not registered. Funding: There was
      no funding.

PMID- 29059294
TI  - Europeanization process impacts the patterns of alcohol consumption in the
      Western Balkans.
AB  - Background: Western Balkan countries exhibit high levels of alcohol consumption,
      which constitutes a serious public health concern. We aimed to quantitatively
      assess the influence of the Europeanization process on levels of alcohol
      consumption in Western Balkans, an issue that has been under-researched. Methods:
      The process of Europeanization was defined as the penetration of European
      dimension, procedures, policy paradigms, beliefs and norms in national arenas of
      politics and policy development. Data about alcohol consumption in six Western
      Balkan countries from 1991 to 2011 were gathered from the World Bank and World
      Health Organization databases. Azerbaijan and Georgia were considered control
      countries. A difference-in-differences approach was used to assess the impact of
      Europeanization process on levels of alcohol consumption. Results: The
      Europeanization process impacts alcohol consumption in Western Balkan countries
      through the European Union directives and tax policies. After starting the
      Europeanization process, the spirits consumption in Croatia and The Former
      Yugoslav Republic of Macedonia decreased by 1.06 litter per capita (95% CI: from 
      1.63 to - 0.49) and 1.02 litter per capita in Serbia (95% CI: from -1.9 to -
      0.1). Conclusion: Our analysis provides useful evidence about the possible
      influence of Europeanization process especially on spirits consumption levels in
      Western Balkans. These findings draw attention to the need to implement new
      policies in order to prevent alcohol health-related harm due to the possible
      increase of wine and beer consumption.

PMID- 29059295
TI  - Treatment with facemask and removable upper appliance versus modified tandem
      traction bow appliance: the effects on mandibular space.
AB  - Objective: The aim of this study was to evaluate and compare the mandibular arch
      posterior space changes in Class III patients treated with facemask (FM) with
      removable upper appliance or modified tandem traction bow appliance (MTTBA).
      Methods: Pre- and post-treatment and pre- and post-observation lateral
      cephalograms of 76 subjects with skeletal and dental Class III malocclusion from
      the period 2000-10 years formed the materials of this study. In the first group,
      25 patients (10 girls, 15 boys; mean age: 10 years, 1 month) were treated with
      MTTBA. The average treatment time was 12 months. In the second group, 26 patients
      were treated (13 girls, 13 boys; mean age: 10 years, 4 months) with a Delaire
      type FM. The average treatment time was 13 months. The remaining 25 children (9
      girls, 16 boys; mean age: 9 years, 8 months) were observed without treatment for
      10 months. ANOVA, Duncan, and paired t-tests were used for statistical
      evaluation. Results: Although ramus width and mandibular posterior space
      increased significantly in all groups, no significant differences were found
      among the groups. Significant increase in tipping of lower molar (L6/GoMe) in the
      MTTBA group showed a significant difference compared with the FM and control
      groups. Significant retroclination of the lower incisors (L1/NB) in the MTTBA and
      FM treatment groups was significantly different compared with the control group.
      Retroclination of lower incisors in the MTTBA group was significantly greater
      than that in the FM group. Conclusions: FM and MTTBA treatment approaches did not
      affect the dimensions of posterior space. Limitations: To generalize the results
      of this study, long term evaluation by considering the third molar position
      should be done.

PMID- 29059296
TI  - Carotid plaque thickness and carotid plaque burden predict future cardiovascular
      events in asymptomatic adult Americans.
AB  - Introduction: Prediction of cardiovascular events improves using imaging, i.e.
      coronary calcium score and ultrasound assessment of carotid plaque. This study
      analysed the predictive value of two ultrasound measures of carotid plaque size:
      carotid plaque thickness and carotid and intima-media thickness (IMT). Methods
      and results: A total of 6102 asymptomatic persons underwent assessment of
      conventional risk factors and imaging by carotid ultrasound. Carotid plaque
      burden (cPB) and maximum carotid plaque thickness (cPTmax) were measured from
      'cross-sectional sweep' video acquisition of the carotid artery. IMT was measured
      from distal common carotid artery images. All participants were followed up for
      ~3 years, and major cardiovascular events (MACE) were collected and adjudicated.
      All data were available for 5808 participants, in whom 216 first MACE events were
      observed. Increasing both cPB and cPTmax were associated with increasing the risk
      of future MACE when compared with participants without carotid atherosclerosis.
      Fully adjusted for risk factors, hazard ratios for cPTmax were 1.96 [95%
      confidence interval (CI) 0.91-4.25, P = 0.015] for primary MACE and 3.13 (95% CI
      1.80-5.51, P < 0.001) for secondary MACE, similar to that of cPB. IMT did not
      improve risk prediction significantly. Non-categorical net reclassification index
      (NRI) for cPTmax was 0.178 (95% CI 0.027-0.299, P = 0.032) for primary MACE and
      0.173 (95% CI 0.109-0.243, P < 0.001) for secondary MACE, which is almost similar
      to cPB. IMT assessment did not result in significant NRI. Conclusion: The simpler
      cPTmax predicted cardiovascular events similarly to the more comprehensive cPB,
      whereas IMT did not. Awaiting true 3D ultrasound technology cPTmax may be a
      simple useful measure for prediction of future ASCVD.

PMID- 29059297
TI  - Association analysis between rs6184 and rs6180 polymorphisms of growth hormone
      receptor gene regarding skeletal-facial profile in a Colombian population.
AB  - Background/Objective: There is strong evidence that genetic factors may affect
      the craniofacial morphology. This study aimed to examine the association between
      the rs6184 and rs6180 polymorphic variants of the growth hormone receptor (GHR)
      gene and skeletal-facial profile in a Colombian population. Subjects/Methods:
      Saliva samples from 306 individuals ranging in age from 15 to 53 (mean 24.33)
      years were collected. Cephalometric parameters were used to categorize the
      participants as Class I, Class II, or Class III skeletal-facial profile. The
      polymerase chain reaction-restriction fragment length polymorphism method was
      used to identify genotypes of the rs6184 and rs6180 single nucleotide
      polymorphisms (SNPs). The association of polymorphisms with the skeletal-facial
      profile was assessed separately and adjusted for confounding using a multivariate
      binary logistic regression model, alongside with analysis of linkage
      disequilibrium and haplotype associations. Results: Although individuals carrying
      the CA genotype of the rs6184 SNP showed both significantly decreased values for
      ANB angle and increased measures concerning mandibular body length and mandibular
      length, no significant differences amongst genotype groups of rs6180 SNP were
      observed. Moreover, chi-square test and logistic regression analysis revealed
      that the CA genotype of rs6184 SNP and the A-A haplotype were highly associated
      with Class III skeletal-facial profile. Conclusions: Although these results do
      not support that rs6180 SNP could be identified as a predictor for skeletal
      facial profile, they suggest that the allele A of rs6184 SNP alone or in
      combination with other SNPs in the GHR gene yields significant horizontal and
      longitudinal variations of the mandibular morphology and might be a
      strong/independent prognostic indicator for Class III skeletal-facial profile in
      the present population.

PMID- 29059298
TI  - Glycemic Control and the Prevalence of Tuberculosis Infection: A Population-based
      Observational Study.
AB  - Background: Several cohort studies demonstrate that diabetics are at increased
      risk for active tuberculosis, and poor glycemic control may exacerbate this risk.
      A higher prevalence of tuberculosis infection at baseline among diabetics may
      partially explain these results; however, no population-based studies have
      investigated this association. Furthermore, whether glycemic control modifies the
      relationship between diabetes and tuberculosis infection, as it does with active
      tuberculosis, is unknown. Methods: Diabetics were diagnosed through physician
      evaluation and using 3 laboratory tests including hemoglobin A1C (HbA1C), fasting
      plasma glucose (FPG), or 2-hour plasma glucose (PG). Tuberculosis infection was
      diagnosed through tuberculin skin tests, and glycemic control was assessed
      linearly and categorically using recommended targets. Results: Among 4215
      participants, the prevalence of tuberculosis infection was 4.1%, 5.5%, and 7.6%
      in nondiabetic, prediabetic, and diabetic participants (Ptrend = .012). In
      multivariate analysis, diabetes was associated with tuberculosis infection
      (adjusted odds ratio [AOR], 1.5; 95% confidence interval [CI], 1.0-2.2). Compared
      to nondiabetics, diabetics who were undiagnosed (AOR, 2.2 and 1.2 in diagnosed
      diabetics), FPG >130 mg/dL (AOR, 2.6 and 1.3 in diabetics with FPG <=130 mg/dL),
      or not on insulin (AOR, 1.7 and 0.8 in diabetics on insulin) had elevated
      tuberculosis infection rates. In a linear dose-response analysis, increasing
      values of FPG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.03), PG (AOR, 1.02 per 1
      mg/dL; 95% CI, 1.01-1.04), and HbA1C (AOR, 1.13 per 1%; 95% CI, 1.04-1.22) all
      predicted tuberculosis infection. Conclusions: Our results suggest glycemic
      control may modify the relationship between tuberculosis infection and diabetes.

PMID- 29059299
TI  - A cautionary tale of sense-antisense gene pairs: independent regulation despite
      inverse correlation of expression.
AB  - Long non-coding RNAs (lncRNAs) have been proven to play important roles in
      diverse cellular processes including the DNA damage response. Nearly 40% of
      annotated lncRNAs are transcribed in antisense direction to other genes and have
      often been implicated in their regulation via transcript- or transcription
      dependent mechanisms. However, it remains unclear whether inverse correlation of
      gene expression would generally point toward a regulatory interaction between the
      genes. Here, we profiled lncRNA and mRNA expression in lung and liver cancer
      cells after exposure to DNA damage. Our analysis revealed two pairs of mRNA
      lncRNA sense-antisense transcripts being inversely expressed upon DNA damage. The
      lncRNA NOP14-AS1 was strongly upregulated upon DNA damage, while the mRNA for
      NOP14 was downregulated, both in a p53-dependent manner. For another pair, the
      lncRNA LIPE-AS1 was downregulated, while its antisense mRNA CEACAM1 was
      upregulated. To test whether as expected the antisense genes would regulate each
      other resulting in this highly significant inverse correlation, we employed
      antisense oligonucleotides and RNAi to study transcript-dependent effects as well
      as dCas9-based transcriptional modulation by CRISPRi/CRISPRa for transcription
      dependent effects. Surprisingly, despite the strong stimulus-dependent inverse
      correlation, our data indicate that neither transcript- nor transcription
      dependent mechanisms explain the inverse regulation of NOP14-AS1:NOP14 or LIPE
      AS1:CEACAM1 expression. Hence, sense-antisense pairs whose expression is strongly
      positively or negatively-correlated can be nonetheless regulated independently.
      This highlights the requirement of individual experimental studies for each
      antisense pair and prohibits drawing conclusions on regulatory mechanisms from
      expression correlations.

PMID- 29059301
TI  - Steady State vs. Pulsatile Blood Pressure Component and Regional Cerebral
      Perfusion.
AB  - BACKGROUND: Arterial blood pressure (BP) can be divided into steady state
      component that is determined by mean arterial pressure and pulsatile component
      that is explored by pulse pressure (PP). We determined relationships between BP
      components and regional cerebral perfusion. METHODS: A total of 52 apparently
      healthy and cognitively normal adults aged 40-60 years were studied. Regional
      cerebral perfusion was measured using functional magnetic resonance imaging (MRI)
      arterial spin labeling technique in 10 a priori regions of interest. RESULTS:
      There were 5 regions with cerebral perfusion values significantly associated with
      either pulsatile BP component (i.e., hippocampus, posterior insula, and central
      white matter) or both steady and pulsatile components (i.e., anterior white
      matter, and occipitoparietal area). After controlling for body mass index,
      education, age, and sex, associations between pulsatile BP components and
      regional cerebral perfusion remained significant in 2 regions (i.e., hippocampus
      and anterior white matter). Multiple linear regression analyses revealed that
      brachial systolic pressure (beta = -0.35, P = 0.03) and PP (beta = -0.36, P =
      0.02) explained 11 and 12% of the variability in hippocampus perfusion,
      independent of the entered covariates. CONCLUSIONS: The present preliminary study
      indicated that pulsatile component of BP was more strongly related to regional
      cerebral perfusion in areas susceptible to cerebrovascular diseases than steady
      state component.

PMID- 29059300
TI  - Thioflavin T binds dimeric parallel-stranded GA-containing non-G-quadruplex DNAs:
      a general approach to lighting up double-stranded scaffolds.
AB  - A molecular rotor thioflavin T (ThT) is usually used as a fluorescent ligand
      specific for G-quadruplexes. Here, we demonstrate that ThT can tightly bind non-G
      quadruplex DNAs with several GA motifs and dimerize them in a parallel double
      stranded mode, accompanied by over 100-fold enhancement in the fluorescence
      emission of ThT. The introduction of reverse Watson-Crick T-A base pairs into
      these dimeric parallel-stranded DNA systems remarkably favors the binding of ThT
      into the pocket between G*G and A*A base pairs, where ThT is encapsulated thereby
      restricting its two rotary aromatic rings in the excited state. A similar
      mechanism is also demonstrated in antiparallel DNA duplexes where several motifs
      of two consecutive G*G wobble base pairs are incorporated and serve as the active
      pockets for ThT binding. The insight into the interactions of ThT with non-G
      quadruplex DNAs allows us to introduce a new concept for constructing DNA-based
      sensors and devices. As proof-of-concept experiments, we design a DNA triplex
      containing GA motifs in its Hoogsteen hydrogen-bonded two parallel strands as a
      pH-driven nanoswitch and two GA-containing parallel duplexes as novel metal
      sensing platforms where C-C and T-T mismatches are included. This work may find
      further applications in biological systems (e.g. disease gene detection) where
      parallel duplex or triplex stretches are involved.

PMID- 29059303
TI  - Prognosis of Masked and White Coat Uncontrolled Hypertension Detected by
      Ambulatory Blood Pressure Monitoring in Elderly Treated Hypertensive Patients.
AB  - BACKGROUND: Prognosis of masked and white coat uncontrolled hypertension (MUCH
      and WCUCH, respectively) detected by ambulatory blood pressure (BP) monitoring is
      incompletely clear in elderly treated hypertensive patients. We evaluated
      prognosis of MUCH and WCUCH identified by ambulatory BP monitoring in this
      setting. METHODS: The occurrence of a composite endpoint was evaluated in 1,191
      elderly treated hypertensive patients. Controlled hypertension (CH) was defined
      as clinic BP <140/90 mm Hg and 24-hour BP <130/80 mm Hg, MUCH as clinic BP
      <140/90 mm Hg and 24-hour BP >=130 and/or >=80 mm Hg, WCUCH as clinic BP >=140
      and/or >=90 mm Hg and 24-hour BP <130/80 mm Hg and sustained uncontrolled
      hypertension (SUCH) as clinic BP >=140 and/or >=90 mm Hg and 24-hour BP >=130
      and/or >=80 mm Hg. RESULTS: MUCH was identified in 142 patients (12% of all the
      population, 34% of those with normal clinic BP) and WCUCH in 230 patients (19% of
      all the population, 30% of those with high clinic BP). During the follow-up (9.1
      +/- 4.9 years, range 0.4-20 years), 392 events occurred. After adjustment for
      various covariates, patients with MUCH (hazard ratio (HR) 1.60, 95% confidence
      interval (CI) 1.12-2.29, P = 0.01) and SUCH (HR 1.81, 95% CI, 1.35-2.42, P <
      0.001) had significantly higher cardiovascular risk than those with CH, whereas
      those with WCUCH (HR 1.09, 95% CI, 0.74-1.60, P = 0.66) had not significantly
      higher risk. CONCLUSIONS: In elderly treated hypertensive patients evaluated by
      ambulatory BP monitoring, compared to individuals with CH, those with MUCH have
      significantly higher risk and those with WCUCH have slightly and not
      significantly higher risk.

PMID- 29059304
TI  - The Etiology of Arteriolar Injury in Malignant Hypertension.

PMID- 29059302
TI  - Office and Home Blood Pressures as Determinants of Electrocardiographic Left
      Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish.
AB  - BACKGROUND: The association of electrocardiographic left ventricular hypertrophy
      (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains
      poorly documented. METHODS: In 225 Black Nigerians and 729 White Flemish, we
      analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of
      ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP
      (duplicate morning and evening readings averaged over 1 week). RESULTS: In
      multivariable analyses, QRS voltage and voltage-duration indexes were generally
      higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more
      prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference
      among women (17.1%). Precordial voltages and voltage-duration products increased
      with office and home systolic BP (SBP), and increases were up to 3-fold steeper
      in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated
      with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26)
      vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for
      office and home BP, respectively, with a significant ethnic gradient (P < 0.05).
      The risk of ECG-LVH increased more with office and home BP in Blacks than Whites.
      CONCLUSIONS: Associations of ECG voltages and voltage-duration products and risk
      of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference
      population. In resource-poor settings of sub-Saharan Africa, the ECG in
      combination with office and home BP is an essential instrument in risk
      stratification across the entire BP range.

PMID- 29059305
TI  - Corrigendum.

PMID- 29059306
TI  - AJH Peer Review 2016.

PMID- 29059307
TI  - Erratum.

PMID- 29059308
TI  - Potential of high-dose cefepime/tazobactam against multiresistant Gram-negative
      pathogens.
AB  - Background: Early beta-lactamase inhibitors were combined with established
      penicillins, but different combinations may be more appropriate to counter
      current beta-lactamase threats, with development facilitated by the US Generating
      Antibiotic Incentives Now (GAIN) Act. Cefepime/tazobactam is especially
      attractive, combining an AmpC-stable cephalosporin with a clinically established
      inhibitor, active against ESBLs and suitable for high-dose administration.
      Methods: Organisms (n = 563) were clinical isolates submitted to the UK national
      reference laboratory. MICs were determined by CLSI agar dilution with tazobactam
      at 4 mg/L and, for a subset, at 8 mg/L. Results: Cefepime/tazobactam 8 + 4 mg/L
      achieved coverage of 96%-100% of Enterobacteriaceae with penicillinases, AmpC,
      ESBL, K1 or OXA-48 beta-lactamases. Even at 1 + 4 mg/L, the combination inhibited
      >94% of isolates with penicillinases, AmpC enzymes or ESBLs. Most
      Enterobacteriaceae with KPC and NDM carbapenemase were resistant at current
      cefepime breakpoints but 80% of those with VIM types were susceptible at 8 + 4
      mg/L. Tazobactam did little to potentiate cefepime against non-fermenter groups,
      though gains were seen against AmpC-producing Acinetobacter spp. and
      Stenotrophomonas maltophilia. Increasing the tazobactam concentration to 8 mg/L
      gave further small increases in activity against Enterobacteriaceae groups.
      Conclusions: High-dose cefepime/tazobactam, justifying an 8 + 4 or 8 + 8 mg/L
      breakpoint, can achieve a carbapenem-like spectrum, with some additional coverage
      of OXA-48 (and maybe VIM) Enterobacteriaceae. Clinical evaluation is warranted.

PMID- 29059309
TI  - Elevated Intraocular Pressure Induces Amyloid-beta Deposition and Tauopathy in
      the Lateral Geniculate Nucleus in a Monkey Model of Glaucoma.
AB  - Purpose: Recent evidence has suggested a potential association between
      Alzheimer's disease (AD) and glaucoma and found significant deposition of amyloid
      beta (Abeta) and Tau protein in the retinas of glaucoma patients. However, no
      coherent finding has emerged regarding the AD-like changes in the central visual
      system (CVS). Studies confirming the presence of Abeta and Tau neuropathology are
      warranted to identify the underlying mechanism that contributes to the visual
      impairment observed in glaucoma. Methods: A chronic glaucoma model was
      established in rhesus monkeys. The retina, optic nerve, CVS including the lateral
      geniculate nucleus (LGN) and primary visual cortex (V1), and cognitive areas
      including the hippocampus (Hpp) were evaluated. Abeta 1-42 and phosphorylated-Tau
      (p-Tau) were tested in the aforementioned structure using immunohistochemistry,
      Western blotting and ELISA, and the neuritic plaques and argyrophilic
      structures/neurofilaments were observed using silver staining and transmission
      electron microscopy (TEM). Results: Immunohistochemistry revealed positive Abeta
      and p-Tau labeling in the LGN. According to Western blotting assay and ELISA,
      Abeta and p-Tau were present in the LGN. Abeta also was expressed weakly in the
      primary visual cortex. In contrast, the hippocampus, which is the most severely
      affected region in AD, showed no positive labeling. Structurally, silver staining
      and TEM revealed neuritic plaques and argyrophilic structures/neurofibrillary
      tangles, in the LGN. Conclusions: For the first time to our knowledge, these data
      collectively establish the existence of hallmark AD-like pathologies in the
      glaucomatous LGN. Our results may provide new targets for developing research
      therapies that will enhance neuroprotection in glaucoma patients.

PMID- 29059310
TI  - Letter to the Editor: Comparison of Alternative Tumor Size Classifications for
      Posterior Uveal Melanomas.

PMID- 29059311
TI  - SOX10 Expression as Well as BRAF and GNAQ/11 Mutations Distinguish Pigmented
      Ciliary Epithelium Neoplasms From Uveal Melanomas.
AB  - Purpose: Adenocarcinomas or adenomas derived from pigmented ciliary epithelium
      (APCE) are exceptionally rare ocular tumors. These tumors have pigmented and
      epithelioid features, and some APCEs are negative for keratin markers and
      positive for melanocytic markers. It is especially difficult to distinguish APCEs
      from uveal melanoma (UM). Accordingly, we examined protein expression and genetic
      mutations associated with APCE to facilitate diagnosis. Methods: Five APCE and 11
      UM samples were obtained from patients during surgical resection at our
      institute. APCE and UM ocular structures were compared comprehensively. Protein
      expression and genetic alterations involved in malignant melanoma were evaluated.
      Results: SOX10 was expressed diffusely in all 11 UMs and in surrounding uveal or
      choroidal melanocytes, but not in the APCEs or nontumorous pigmented epithelia.
      Additionally, the expression patterns of cytokeratins and melanocytic markers
      differed between UMs and APCEs. We identified BRAF V600E mutations in four of
      five APCE samples, but not in the 11 UM samples. Moreover, GNAQ or GNA11
      mutations were found in 10 of the 11 UM samples, but not in APCE samples. NRAS
      mutations were not observed in either tumor group examined. Conclusions: APCE is
      a separate entity distinguished from UM by the absence of SOX10 expression and
      presence of the BRAF V600E mutation. These results have implications for
      diagnosis, providing a means to distinguish between UM and APCE.

PMID- 29059312
TI  - Conjunctival Melanoma in Chinese Patients: Local Recurrence, Metastasis,
      Mortality, and Comparisons With Caucasian Patients.
AB  - Purpose: To evaluate the prognosis in Chinese patients with conjunctival melanoma
      and determine its predictors. Further, to explore the racial differences in
      clinical characteristics and outcomes between Chinese and Caucasian patients.
      Methods: This cohort study included 57 eyes of 57 consecutive patients with
      pathologically verified conjunctival melanoma between 1996 and 2016. Medical
      records were reviewed for factors associated with the local recurrence,
      metastasis, and tumor-related mortality. All eligible patients were followed up
      for these three outcome measures. The demographic data, clinical characteristics,
      and outcomes were compared between Chinese and Caucasian patients. Results: The
      mean follow-up period was 52.2 +/- 49.4 months. Among the total 57 patients, 29
      (51%) patients experienced local recurrence. The 1-, 5-, and 10-year recurrence
      rate was 31.0%, 59.7%, and 66.4%, respectively. Treatment complications detected
      in the follow-up included dry eye (32, 56.1%), irregular eyelid margin (25,
      43.9%), eyelid retraction (18, 31.6%), blepharoptosis (9, 15.8%), mixed
      pigmentation of the tarsus reconstructed by mucosal membrane graft, corneal
      opacities (6, 10.5%), and symblepharon (2, 3.5%). Twenty (35%) patients developed
      metastasis. The 1-, 5-, and 10-year metastasis rate was 16.7%, 38.7%, and 50.9%,
      respectively. Fourteen (25%) patients died of conjunctival melanoma, with a
      median survival time of 24 months. The 1-, 5-, and 10-year tumor-related
      mortality was 3.8%, 30.5%, and 37.4%, respectively. Tumor hemorrhage is an
      independent risk factor for tumor-related death (hazard ratio [HR]: 18.81, P =
      0.01) and metastasis (HR: 4.57, P = 0.02). Significant differences were noted
      between Chinese and Caucasians patients from America, Germany, and England in
      demographics, clinical characteristics, and outcomes. Compared to Caucasians,
      Chinese patients tended to have more male cases (P < 0.01) and to be younger (P =
      0.03). At initial presentation, more Chinese patients had de novo tumor origin (P
      < 0.01), epithelioid cell type (P < 0.01), nonbulbar tumor location (P < 0.01),
      greater basal diameter (P = 0.04), multifocal tumor (P < 0.01), feeder vessels (P
      < 0.01), eyelid (P < 0.01) and orbit involvement (P < 0.01), and advanced T
      stages (P < 0.01). Over a similar follow-up period with Caucasians patients (52.2
      vs. 52 months, P = 0.97), a significantly larger proportion of Chinese patients
      exhibited eyelid invasion (P = 0.04) and orbital invasion (P < 0.01) at follow
      up, local recurrence (P < 0.01), metastasis (P < 0.01), and tumor-related death
      (P < 0.01). Conclusions: Conjunctival melanoma is a rare malignancy with great
      potential for mortality in Chinese. Special attention should be paid to patients
      with tumor hemorrhage. Compared to Caucasians, Chinese patients exhibit more
      aggressive clinical signs with compromised prognosis.

PMID- 29059313
TI  - Hypoxic, Hypercapnic, and Hyperoxic Responses of the Optic Nerve Head and
      Subfoveal Choroid Blood Flow in Healthy Humans.
AB  - Purpose: To investigate the impact of different gas mixtures (hyperoxia, hypoxia,
      and hypercapnia) on the optic nerve head (ONH) and choroidal (Ch) hemodynamics.
      Methods: Twenty-three healthy subjects (28 +/- 6 years) took part in the study.
      Variations in inspired oxygen and carbon dioxide fraction were produced by a gas
      mixing device. Arterial oxygen saturation (SpO2) was measured continuously using
      a transcutaneous sensor and end-tidal carbon dioxide partial pressure by
      capnography. The experiment comprised three successive periods: 3-minute baseline
      (room air breathing), 15-minute gas mixture inhalation (normocapnic hypoxia,
      hypercapnia, or hyperoxia), and 15-minute recovery (room air breathing). Laser
      Doppler flowmeter parameters-velocity (VEL), volume (VOL), and flow (BF) of red
      blood cells-were measured. Two-way ANOVAs were performed for statistical
      analysis. Results: In response to hyperoxia, ONHBF significantly decreased by 
      18% +/- 6% (P = 0.04) from baseline, due to significant changes in VEL (-12% +/-
      3% P = 0.0002). During hypoxia at 85% SpO2, ONH VEL increased by +12% +/- 3% (P =
      0.0009), whereas VOL and BF did not change significantly. ChBF significantly
      increased by +7% +/- 2% (P = 0.004) in response to hypoxia, due to significant
      changes in VEL +5% +/- 2% (P = 0.03). Both Ch and ONHBFs did not vary
      significantly in response to hypercapnia. Conclusions: The magnitude of the blood
      flow response is the most significant during hyperoxia for ONH and hypoxia for
      ChBF. For ONHBF, a 37% difference between hyperoxia and hypoxia can be useful
      when vasoreactivity to O2 will be tested in patients.

PMID- 29059314
TI  - Foveal and Peripapillary Vascular Decrement in Migraine With Aura Demonstrated by
      Optical Coherence Tomography Angiography.
AB  - Purpose: Migraine, particularly with aura, has been associated with ocular and
      systemic ischemic complications, but there are limited data on the ocular
      vasculature in migraine. We used optical coherence tomography angiography (OCTA)
      to assess perfusion of the macula and optic nerve in migraine patients, with (MA)
      and without (MO) aura, compared to healthy controls (HC). Methods: We recruited
      15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39
      years) participants from neurology and neuro-ophthalmology clinics. Participants
      underwent optical coherence tomography and 3 * 3 mm OCTA of the macula and optic
      nerve. Foveal avascular zone area was automatically measured using AngioVue
      software, and vessel density was calculated as blood vessel length divided by
      scan area (mm-1) after skeletonization of OCTA images. Results: On macular OCTA,
      MA participants had an enlarged foveal avascular zone area when compared with HC
      (0.300 +/- 0.019 vs. 0.220 +/- 0.066 mm2, P = 0.006). In addition, superficial
      foveal vessel density was decreased in MA participants when compared with MO
      participants (7.8 +/- 0.31 vs. 9.3 +/- 0.44, P = 0.04) and HC (7.8 +/- 0.31 vs.
      9.4 +/- 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had
      reduced superior peripapillary vessel density when compared with the MO
      participants (12.0 +/- 0.45 vs. 14.0 +/- 0.38 mm-1, P = 0.031) and HC (12.0 +/-
      0.45 vs. 14.1 +/- 0.53 mm-1, P = 0.035). There were no significant differences
      between the MO and HC groups. Conclusions: Migraine with, but not without, aura
      was associated with foveal and peripapillary vascular decrements, which may
      possibly mediate increased risk of ocular and systemic vascular complications in
      these patients. OCTA could potentially be useful as a biomarker for migraine with
      aura.

PMID- 29059315
TI  - The Use of Botulinum Toxin to Treat Infantile Esotropia: A Systematic Review With
      Meta-Analysis.
AB  - Purpose: The purpose of this review was to examine the efficacy of botulinum
      toxin in the treatment of infantile esotropia and to evaluate the average
      response of BT and its complication rates. Methods: A research was performed in
      the Latin American and Caribbean Literature on Health Sciences (LILACS), MEDLINE,
      and Cochrane Central Register of Controlled Trial (CENTRAL). The database was
      searched between December 28, 2016 and January 30, 2017. The selection was
      restricted to articles published in English, Spanish, or Portuguese. There were
      no date restrictions in the search. Results: Nine studies were eligible for
      inclusion. The grouped success rate of BT treatment in infantile esotropia was
      76% (95% confidence interval [CI]: 61%-89%). For the success rate, I2 of 94.25%
      was observed, indicating a high heterogeneity (P < 0.001). The complication rates
      were also analyzed. The grouped consecutive exotropia (XT) rate was 1% (95% CI:
      0%-2%). The grouped ptosis rate was 27% (95% CI: 21%-33%). The grouped vertical
      deviation rate was 12% (95% CI: 4%-22%). The mean change of the deviation after
      BT injection was -30.7 (95% CI: -37.7, -23.8), demonstrating a significant
      improvement in alignment. Conclusions: Botulinum toxin injection into medial
      recti muscles reveals to be a safe procedure and a valuable alternative to
      strabismus surgery in congenital esotropia, especially in moderate deviations.

PMID- 29059316
TI  - Inter-genotypic differences in drought tolerance of maritime pine are modified by
      elevated [CO2].
AB  - Background and Aims: Despite the importance of growth [CO 2 ] and water
      availability for tree growth and survival, little information is available on how
      the interplay of these two factors can shape intraspecific patterns of functional
      variation in tree species, particularly for conifers. The main objective of the
      study was to test whether the range of realized drought tolerance within the
      species can be affected by elevated [CO 2 ]. Methods: Intraspecific variability
      in leaf gas exchange, growth rate and other leaf functional traits were studied
      in clones of maritime pine. A factorial experiment including water availability,
      growth [CO 2 ] and four different genotypes was conducted in growth rooms. A
      'water deficit' treatment was imposed by applying a cycle of progressive soil
      water depletion and recovery at two levels of growth [CO 2 ]: 'ambient [CO 2 ]'
      (aCO 2 400 MUmol mol -1 ) and 'elevated [CO 2 ]' (eCO 2 800 MUmol mol -1 ). Key
      Results: eCO2 had a neutral effect on the impact of drought on growth and leaf
      gas exchange of the most drought-sensitive genotypes while it aggravated the
      impact of drought on the most drought-tolerant genotypes at aCO2. Thus, eCO2
      attenuated genotypic differences in drought tolerance as compared with those
      observed at aCO2. Genotypic variation at both levels of growth [CO2] was found in
      specific leaf area and leaf nitrogen content but not in other physiological leaf
      traits such as intrinsic water use efficiency and leaf osmotic potential. eCO2
      increased Delta 13 C but had no significant effect on delta 18 O. This effect did
      not interact with the impact of drought, which increased delta 18 O and decreased
      Delta 13 C. Nevertheless, correlations between Delta 13 C and delta 18 O
      indicated the non-stomatal component of water use efficiency in this species can
      be particularly sensitive to drought. Conclusions: Evidence from this study
      suggests elevated [CO 2 ] can modify current ranges of drought tolerance within
      tree species.

PMID- 29059317
TI  - Flood tolerance of Glyceria fluitans: the importance of cuticle hydrophobicity,
      permeability and leaf gas films for underwater gas exchange.
AB  - Background and Aims: Floating sweet-grass ( Glyceria fluitans ) can form aerial
      as well as floating leaves, and these both possess superhydrophobic cuticles, so
      that gas films are retained when submerged. However, only the adaxial side of the
      floating leaves is superhydrophobic, so the abaxial side is directly in contact
      with the water. The aim of this study was to assess the effect of these different
      gas films on underwater net photosynthesis ( P N ) and dark respiration ( R D ).
      Methods: Evolution of O 2 was used to measure underwater P N in relation to
      dissolved CO 2 on leaf segments with or without gas films, and O 2
      microelectrodes were used to assess cuticle resistance of floating leaves to O 2
      uptake in the dark. Key Results: The adaxial side of aerial leaves was more
      hydrophobic than the abaxial side and also initially retained a thicker gas film
      when submerged. Underwater P N vs. dissolved CO 2 of aerial leaf segments with
      gas films had a K m of 172 mmol CO 2 m -3 and a P max of 7.1 MUmol O 2 m -2 s -1
      , and the leaf gas films reduced the apparent resistance to CO 2 uptake 12-fold.
      Underwater P N of floating leaves measured at 700 mmol CO 2 m -3 was 1.5-fold
      higher than P N of aerial leaves. The floating leaves had significantly lower
      cuticle resistance to dark O 2 uptake on the wettable abaxial side compared with
      the superhydrophobic adaxial side. Conclusions: Glyceria fluitans showed high
      rates of underwater P N and these were obtained at environmentally relevant CO 2
      concentrations. It appears that the floating leaves possess both aquatic and
      terrestrial properties and thus have 'the best of both worlds' so that floating
      leaves are particularly adapted to situations where the plant is partially
      submerged and occasionally experiences complete submergence.

PMID- 29059318
TI  - Plant Cuttings: news in Botany.

PMID- 29059319
TI  - Political priorities and public health services in English local authorities: the
      case of tobacco control and smoking cessation services.
AB  - Background: Since 2013, local authorities in England have been responsible for
      public health including smoking cessation services. Methods: Online surveys of
      tobacco control leads in English local authorities were conducted in 2014 (76%
      response rate, n = 116), 2015 (82% response rate, n = 124) and 2016 (85% response
      rate, n = 129). Results: A high priority for tobacco control was reported in 17%
      of local authorities in 2014, rising to 27% in 2016. A low priority for tobacco
      control was reported in 4% of local authorities in 2014, rising to 11% in 2016.
      Budgets for smoking cessation services were cut in 16% of local authorities in
      2014, 39% in 2015 and 59% in 2016. In 2016, budgets were cut in all local
      authorities where the priority given to tobacco control was perceived to be low
      and in 40% of the local authorities where it was perceived to be high. Cuts in
      smoking cessation budgets were principally due to cuts to the public health grant
      and wider cuts to local authority budgets. Conclusions: At a time of significant
      cost pressure, political support for tobacco control in English local authorities
      mitigates but does not remove the risk of cuts to budgets for smoking cessation
      services.

PMID- 29059320
TI  - DiseaseEnhancer: a resource of human disease-associated enhancer catalog.
AB  - Large-scale sequencing studies discovered substantial genetic variants occurring
      in enhancers which regulate genes via long range chromatin interactions.
      Importantly, such variants could affect enhancer regulation by changing
      transcription factor bindings or enhancer hijacking, and in turn, make an
      essential contribution to disease progression. To facilitate better usage of
      published data and exploring enhancer deregulation in various human diseases, we
      created DiseaseEnhancer (http://biocc.hrbmu.edu.cn/DiseaseEnhancer/), a manually
      curated database for disease-associated enhancers. As of July 2017,
      DiseaseEnhancer includes 847 disease-associated enhancers in 143 human diseases.
      Database features include basic enhancer information (i.e. genomic location and
      target genes); disease types; associated variants on the enhancer and their
      mediated phenotypes (i.e. gain/loss of enhancer and the alterations of
      transcription factor bindings). We also include a feature on our website to
      export any query results into a file and download the full database.
      DiseaseEnhancer provides a promising avenue for researchers to facilitate the
      understanding of enhancer deregulation in disease pathogenesis, and identify new
      biomarkers for disease diagnosis and therapy.

PMID- 29059321
TI  - Confronting the catalytic dark matter encoded by sequenced genomes.
AB  - The post-genomic era has provided researchers with a deluge of protein sequences.
      However, a significant fraction of the proteins encoded by sequenced genomes
      remains without an identified function. Here, we aim at determining how many
      enzymes of uncertain or unknown function are still present in the Saccharomyces
      cerevisiae and human proteomes. Using information available in the Swiss-Prot,
      BRENDA and KEGG databases in combination with a Hidden Markov Model-based method,
      we estimate that >600 yeast and 2000 human proteins (>30% of their proteins of
      unknown function) are enzymes whose precise function(s) remain(s) to be
      determined. This illustrates the impressive scale of the 'unknown enzyme
      problem'. We extensively review classical biochemical as well as more recent
      systematic experimental and computational approaches that can be used to support
      enzyme function discovery research. Finally, we discuss the possible roles of the
      elusive catalysts in light of recent developments in the fields of enzymology and
      metabolism as well as the significance of the unknown enzyme problem in the
      context of metabolic modeling, metabolic engineering and rare disease research.

PMID- 29059322
TI  - Cis-regulatory landscapes of four cell types of the retina.
AB  - The retina is composed of ~50 cell-types with specific functions for the process
      of vision. Identification of the cis-regulatory elements active in retinal cell
      types is key to elucidate the networks controlling this diversity. Here, we
      combined transcriptome and epigenome profiling to map the regulatory landscape of
      four cell-types isolated from mouse retinas including rod and cone photoreceptors
      as well as rare inter-neuron populations such as horizontal and starburst
      amacrine cells. Integration of this information reveals sequence determinants and
      candidate transcription factors for controlling cellular specialization.
      Additionally, we refined parallel reporter assays to enable studying the
      transcriptional activity of large collection of sequences in individual cell
      types isolated from a tissue. We provide proof of concept for this approach and
      its scalability by characterizing the transcriptional capacity of several hundred
      putative regulatory sequences within individual retinal cell-types. This
      generates a catalogue of cis-regulatory regions active in retinal cell types and
      we further demonstrate their utility as potential resource for cellular tagging
      and manipulation.

PMID- 29059324
TI  - Xenbase: a genomic, epigenomic and transcriptomic model organism database.
AB  - Xenbase (www.xenbase.org) is an online resource for researchers utilizing Xenopus
      laevis and Xenopus tropicalis, and for biomedical scientists seeking access to
      data generated with these model systems. Content is aggregated from a variety of
      external resources and also generated by in-house curation of scientific
      literature and bioinformatic analyses. Over the past two years many new types of
      content have been added along with new tools and functionalities to reflect the
      impact of high-throughput sequencing. These include new genomes for both
      supported species (each with chromosome scale assemblies), new genome
      annotations, genome segmentation, dynamic and interactive visualization for RNA
      Seq data, updated ChIP-Seq mapping, GO terms, protein interaction data, ORFeome
      support, and improved connectivity to other biomedical and bioinformatic
      resources.

PMID- 29059323
TI  - FANCI and FANCD2 have common as well as independent functions during the cellular
      replication stress response.
AB  - Fanconi anemia (FA) is an inherited cancer predisposition syndrome characterized
      by cellular hypersensitivity to DNA interstrand crosslinks (ICLs). To repair
      these lesions, the FA proteins act in a linear hierarchy: following ICL detection
      on chromatin, the FA core complex monoubiquitinates and recruits the central
      FANCI and FANCD2 proteins that subsequently coordinate ICL removal and repair of
      the ensuing DNA double-stranded break by homology-dependent repair (HDR). FANCD2
      also functions during the replication stress response by mediating the restart of
      temporarily stalled replication forks thereby suppressing the firing of new
      replication origins. To address if FANCI is also involved in these FANCD2
      dependent mechanisms, we generated isogenic FANCI-, FANCD2- and FANCI:FANCD2
      double-null cells. We show that FANCI and FANCD2 are partially independent
      regarding their protein stability, nuclear localization and chromatin recruitment
      and contribute independently to cellular proliferation. Simultaneously, FANCD2
      but not FANCI-plays a major role in HDR-mediated replication restart and in
      suppressing new origin firing. Consistent with this observation, deficiencies in
      HDR-mediated DNA DSB repair can be overcome by stabilizing RAD51 filament
      formation in cells lacking functional FANCD2. We propose that FANCI and FANCD2
      have partially non-overlapping and possibly even opposing roles during the
      replication stress response.

PMID- 29059325
TI  - Dormant origins and fork protection mechanisms rescue sister forks arrested by
      transcription.
AB  - The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of
      replication forks encountering transcription by removing RNA-DNA hybrids. Here we
      show that, in sen1 mutants, when a replication fork clashes head-on with
      transcription is arrested and, as a consequence, the progression of the sister
      fork moving in the opposite direction within the same replicon is also impaired.
      Therefore, sister forks remain coupled when one of the two forks is arrested by
      transcription, a fate different from that experienced by forks encountering
      Double Strand Breaks. We also show that dormant origins of replication are
      activated to ensure DNA synthesis in the proximity to the forks arrested by
      transcription. Dormant origin firing is not inhibited by the replication
      checkpoint, rather dormant origins are fired if they cannot be timely inactivated
      by passive replication. In sen1 mutants, the Mre11 and Mrc1-Ctf4 complexes
      protect the forks arrested by transcription from processing mediated by the Exo1
      nuclease. Thus, a harmless head-on replication-transcription clash resolution
      requires the fine-tuning of origin firing and coordination among Sen1, Exo1,
      Mre11 and Mrc1-Ctf4 complexes.

PMID- 29059326
TI  - Kinetics of Human Mutant Tau Prion Formation in the Brains of 2 Transgenic Mouse
      Lines.
AB  - Importance: Accumulation of the protein tau is a defining characteristic of
      several neurodegenerative diseases. Thorough assessment of transgenic (Tg) mouse
      lines that replicate this process is critical for establishing the models used
      for testing anti-tau therapeutics in vivo. Objective: To define a consistent
      mouse model of disease for use in future compound efficacy studies. Design,
      Setting, and Participants: In this time course study, cohorts of Tg and control
      mice were euthanized at defined intervals. Collected brains were bisected down
      the midline. One half was frozen and used to measure the tau prion content, while
      the other half was fixed for immunostaining with anti-tau antibodies. All mice
      were maintained at the Hunters Point Animal Facility at the University of
      California, San Francisco, and all experiments were performed at the Mission Bay
      Campus of the University of California, San Francisco. Study animals were PS19,
      homozygous and hemizygous Tg(MAPT*P301S), and B6/J mice. The study dates were
      August 9, 2010, to October 3, 2016. Main Outcomes and Measures: Tau prions were
      measured using a cell-based assay. Neuropathology was measured by determining the
      percentage area positive for immunostaining in defined brain regions. A separate
      cohort of mice was aged until each mouse developed neurological signs as
      determined by trained animal technicians to assess mortality. Results: A total of
      1035 mice were used in this time course study. These included PS19 mice (51.2%
      [126 of 246] male and 48.8% [120 of 246] female), Tg(MAPT*P301S+/+) mice (52.3%
      [216 of 413] male, 43.8% [181 of 413] female, and 3.9% [16 of 413] undetermined),
      Tg(MAPT*P301S+/-) mice (51.8% [101 of 195] male and 48.2% [94 of 195] female),
      and B6/J mice (49.7% [90 of 181] male and 50.3% [91 of 181] female). While
      considerable interanimal variability in neuropathology, disease onset, and tau
      prion formation in the PS19 mice was observed, all 3 measures of disease were
      more uniform in the Tg(MAPT*P301S+/+) mice. Comparing tau prion formation in
      Tg(MAPT*P301S+/+) mice with B6/J controls, the 95% CIs for the 2 mouse lines
      diverged before age 5 weeks, and significant (P < .05) neuropathology in the
      hindbrain of 24-week-old mice was quantifiable. Conclusions and Relevance: The
      assessment of disease progression using 3 criteria showed that disease onset in
      PS19 mice is too variable to obtain reliable measurements for drug discovery
      research. However, the reproducibility of tau prion formation in young
      Tg(MAPT*P301S+/+) mice establishes a rapid assay for compound efficacy in vivo.

PMID- 29059327
TI  - Evaluation of fluorescence in situ hybridization techniques to study long non
      coding RNA expression in cultured cells.
AB  - Deciphering the functions of long non-coding RNAs (lncRNAs) is facilitated by
      visualization of their subcellular localization using in situ hybridization (ISH)
      techniques. We evaluated four different ISH methods for detection of MALAT1 and
      CYTOR in cultured cells: a multiple probe detection approach with or without
      enzymatic signal amplification, a branched-DNA (bDNA) probe and an LNA-modified
      probe with enzymatic signal amplification. All four methods adequately stained
      MALAT1 in the nucleus in all of three cell lines investigated, HeLa, NHDF and
      T47D, and three of the methods detected the less expressed CYTOR. The sensitivity
      of the four ISH methods was evaluated by image analysis. In all three cell lines,
      the two methods involving enzymatic amplification gave the most intense MALAT1
      signal, but the signal-to-background ratios were not different. CYTOR was best
      detected using the bDNA method. All four ISH methods showed significantly reduced
      MALAT1 signal in knock-out cells, and siRNA-induced knock-down of CYTOR resulted
      in significantly reduced CYTOR ISH signal, indicating good specificity of the
      probe designs and detection systems. Our data suggest that the ISH methods allow
      detection of both abundant and less abundantly expressed lncRNAs, although the
      latter required the use of the most specific and sensitive probe detection
      system.

PMID- 29059329
TI  - Short-Term Repeatability of Noninvasive Aortic Pulse Wave Velocity Assessment:
      Comparison Between Methods and Devices.
AB  - BACKGROUND: Aortic pulse wave velocity (PWV) is an indirect index of arterial
      stiffness and an independent cardiovascular risk factor. Consistency of PWV
      assessment over time is thus an essential feature for its clinical application.
      However, studies providing a comparative estimate of the reproducibility of PWV
      across different noninvasive devices are lacking, especially in the elderly and
      in individuals at high cardiovascular risk. METHODS: Aimed at filling this gap,
      short-term repeatability of PWV, estimated with 6 different devices (Complior
      Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph),
      was evaluated in 102 high cardiovascular risk patients hospitalized for suspected
      coronary artery disease (72 males, 65 +/- 13 years). PWV was measured in a single
      session twice, at 15-minute interval, and its reproducibility was assessed though
      coefficient of variation (CV), coefficient of repeatability, and intraclass
      correlation coefficient. RESULTS: The CV of PWV, measured with any of these
      devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV =
      5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral
      PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and
      SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in
      subjects with higher carotid-femoral PWV. The differences in PWV between repeated
      measurements, except for the Mobil-O-Graph, did not depend on short-term
      variations of mean blood pressure or heart rate. CONCLUSIONS: Our study shows
      that the short-term repeatability of PWV measures is good but not homogenous
      across different devices and at different PWV values. These findings, obtained in
      patients at high cardiovascular risk, may be relevant when evaluating the
      prognostic importance of PWV.

PMID- 29059330
TI  - Sex Differences in Subjective Responses To Moderate Versus Very Low Nicotine
      Content Cigarettes.
AB  - Introduction: Men and women may be differentially sensitive to the acute
      perceptual responses to smoking cigarettes that vary in nicotine content ("dose")
      but are matched on non-nicotine constituents. Methods: Dependent adult smokers
      (43 M, 31 F) took four controlled puffs from Spectrum research cigarettes that
      were moderate (16-17 mg/g) or very low (0.4 mg/g) in nicotine content, and
      matched on "tar." To ensure reliable responses, each cigarette was administered
      singly five times in random order under blind conditions, with one or the other
      provided every 15 minutes over a 2.5-hour session following overnight abstinence.
      Subjective perceptions (eg, "satisfying", "how much nicotine") were rated after
      each cigarette. Results: Subjective ratings differed due to cigarette nicotine
      content, as expected, and did so differentially between men and women. The
      interaction of nicotine content by sex was significant for most rated subjective
      perceptions of the cigarette, as multivariate analyses showed that differences
      due to nicotine content were highly significant for men (p < .001) but only
      marginal for women (p = .08). Conclusions: Relative to men, women's subjective
      responses to acute smoking are less sensitive to differences in cigarette
      nicotine content. To our knowledge, this is the first comparison of sex
      differences in response to very carefully controlled doses of smoked nicotine per
      se. Further research should examine possible sex differences in nicotine dosing
      administered by other smoked and nonsmoked methods, as well as the developmental
      pattern of these differences during onset and during cessation of dependent
      smoking. Implications: Subjective perceptions of smoking cigarettes varying in
      nicotine contents differ between men and women. These results with research
      cigarettes are similar to other studies with carefully dosed nicotine
      administration by other means, supporting the notion that women, relative to men,
      are less sensitive to pharmacological factors and more sensitive to
      nonpharmacological factors in acute cigarette smoking. Future studies are
      warranted to examine sex differences in other responses to controlled nicotine
      intake via smoking, and via other smoked and nonsmoked methods of administering
      nicotine doses.

PMID- 29059331
TI  - Automated influenza case detection for public health surveillance and clinical
      diagnosis using dynamic influenza prevalence method.
AB  - Objectives: To assess the performance of a Bayesian case detector (BCD) for
      influenza surveillance and clinical diagnosis. Methods: BCD uses a Bayesian
      network classifier to compute the posterior probability of a patient having
      influenza based on 31 findings from narrative clinical notes. To assess the
      potential for disease surveillance, we calculated area under the receiver
      operating characteristic curve (AUC) to indicate BCD's ability to differentiate
      between influenza and non-influenza encounters in emergency department settings.
      To assess the potential for clinical diagnosis, we measured AUC for diagnosing
      influenza cases among encounters having influenza-like illnesses. We also
      evaluated the performance of BCD using dynamically estimated influenza
      prevalence, and measured sensitivity, specificity and positive predictive value.
      Results: For influenza surveillance, BCD differentiated between influenza and non
      influenza encounters well with an AUC of 0.90 and 0.97 with dynamic influenza
      prevalence (P < 0.0001). For clinical diagnosis, the addition of dynamic
      influenza prevalence to BCD significantly improved AUC from 0.63 to 0.85 to
      distinguish influenza from other causes of influenza-like illness. Conclusions
      and policy implications: BCD can serve as an influenza surveillance and a
      differential diagnosis tool via our dynamic prevalence approach. It enhances the
      communication between public health and clinical practice.

PMID- 29059328
TI  - RecQ helicase triggers a binding mode change in the SSB-DNA complex to
      efficiently initiate DNA unwinding.
AB  - The single-stranded DNA binding protein (SSB) of Escherichia coli plays essential
      roles in maintaining genome integrity by sequestering ssDNA and mediating DNA
      processing pathways through interactions with DNA-processing enzymes. Despite its
      DNA-sequestering properties, SSB stimulates the DNA processing activities of some
      of its binding partners. One example is the genome maintenance protein RecQ
      helicase. Here, we determine the mechanistic details of the RecQ-SSB interaction
      using single-molecule magnetic tweezers and rapid kinetic experiments. Our
      results reveal that the SSB-RecQ interaction changes the binding mode of SSB,
      thereby allowing RecQ to gain access to ssDNA and facilitating DNA unwinding.
      Conversely, the interaction of RecQ with the SSB C-terminal tail increases the on
      rate of RecQ-DNA binding and has a modest stimulatory effect on the unwinding
      rate of RecQ. We propose that this bidirectional communication promotes efficient
      DNA processing and explains how SSB stimulates rather than inhibits RecQ
      activity.

PMID- 29059332
TI  - Combining IVUS and Optical Coherence Tomography for More Accurate Coronary Cap
      Thickness Quantification and Stress/Strain Calculations: A Patient-Specific Three
      Dimensional Fluid-Structure Interaction Modeling Approach.
AB  - Accurate cap thickness and stress/strain quantifications are of fundamental
      importance for vulnerable plaque research. Virtual histology intravascular
      ultrasound (VH-IVUS) sets cap thickness to zero when cap is under resolution
      limit and IVUS does not see it. An innovative modeling approach combining IVUS
      and optical coherence tomography (OCT) is introduced for cap thickness
      quantification and more accurate cap stress/strain calculations. In vivo IVUS and
      OCT coronary plaque data were acquired with informed consent obtained. IVUS and
      OCT images were merged to form the IVUS + OCT data set, with biplane angiography
      providing three-dimensional (3D) vessel curvature. For components where VH-IVUS
      set zero cap thickness (i.e., no cap), a cap was added with minimum cap thickness
      set as 50 and 180 MUm to generate IVUS50 and IVUS180 data sets for model
      construction, respectively. 3D fluid-structure interaction (FSI) models based on
      IVUS + OCT, IVUS50, and IVUS180 data sets were constructed to investigate cap
      thickness impact on stress/strain calculations. Compared to IVUS + OCT, IVUS50
      underestimated mean cap thickness (27 slices) by 34.5%, overestimated mean cap
      stress by 45.8%, (96.4 versus 66.1 kPa). IVUS50 maximum cap stress was 59.2%
      higher than that from IVUS + OCT model (564.2 versus 354.5 kPa). Differences
      between IVUS and IVUS + OCT models for cap strain and flow shear stress (FSS)
      were modest (cap strain <12%; FSS <6%). IVUS + OCT data and models could provide
      more accurate cap thickness and stress/strain calculations which will serve as
      basis for further plaque investigations.

PMID- 29059333
TI  - The AraGWAS Catalog: a curated and standardized Arabidopsis thaliana GWAS
      catalog.
AB  - The abundance of high-quality genotype and phenotype data for the model organism
      Arabidopsis thaliana enables scientists to study the genetic architecture of many
      complex traits at an unprecedented level of detail using genome-wide association
      studies (GWAS). GWAS have been a great success in A. thaliana and many SNP-trait
      associations have been published. With the AraGWAS Catalog
      (https://aragwas.1001genomes.org) we provide a publicly available, manually
      curated and standardized GWAS catalog for all publicly available phenotypes from
      the central A. thaliana phenotype repository, AraPheno. All GWAS have been
      recomputed on the latest imputed genotype release of the 1001 Genomes Consortium
      using a standardized GWAS pipeline to ensure comparability between results. The
      catalog includes currently 167 phenotypes and more than 222 000 SNP-trait
      associations with P < 10-4, of which 3887 are significantly associated using
      permutation-based thresholds. The AraGWAS Catalog can be accessed via a modern
      web-interface and provides various features to easily access, download and
      visualize the results and summary statistics across GWAS.

PMID- 29059334
TI  - The MetaCyc database of metabolic pathways and enzymes.
AB  - MetaCyc (https://MetaCyc.org) is a comprehensive reference database of metabolic
      pathways and enzymes from all domains of life. It contains more than 2570
      pathways derived from >54 000 publications, making it the largest curated
      collection of metabolic pathways. The data in MetaCyc is strictly evidence-based
      and richly curated, resulting in an encyclopedic reference tool for metabolism.
      MetaCyc is also used as a knowledge base for generating thousands of organism
      specific Pathway/Genome Databases (PGDBs), which are available in the BioCyc
      (https://BioCyc.org) and other PGDB collections. This article provides an update
      on the developments in MetaCyc during the past two years, including the expansion
      of data and addition of new features.

PMID- 29059335
TI  - Health Care Utilization and Expenditures Attributable to Smokeless Tobacco Use
      Among US Adults.
AB  - Introduction: This study estimated the health care utilization and expenditures
      attributable to the use of smokeless tobacco (ST) which includes chewing tobacco,
      snuff, dip, snus, and dissolvable tobacco among US adults aged 18 and older.
      Methods: We used data from the 2012-2015 National Health Interview Surveys (n =
      139451 adults) to estimate a zero-inflated Poisson (ZIP) regression model on four
      health care utilization measures among US adults (hospital nights, emergency room
      [ER] visits, doctor visits, and home care visits) specified as a function of
      tobacco use status, and other covariates. Tobacco use status was classified into
      four categories: current ST users, former ST users, non-ST tobacco users, and
      never tobacco users. ST-attributable utilization was calculated based on the
      estimated ZIP model using an "excess utilization" approach. It was then
      multiplied by the unit cost estimated from the 2014 Medical Expenditures Panel
      Survey data to derive ST-attributable health care expenditures. Results: During
      2012-2015, 2.1% of adults were current ST users and 7.7% were former ST users. ST
      attributable health care utilization amounted to 681000 hospital nights, 624000
      ER visits, and 4.6 million doctor visits per year (home care visits results were
      not significant). This resulted in annual excess expenditures of $1.8 billion for
      hospitalizations, $0.7 billion for ER visits, and $0.9 billion for doctor visits,
      totaling over $3.4 billion (in 2014 dollars). Conclusion: Comprehensive tobacco
      control policies and interventions are needed to reduce ST use and the associated
      health care burden. Implications: This is the first study to assess the impact of
      ST use on health care burden in the United States. Findings indicate that excess
      annual health care expenditures attributable to ST use for US adults were $3.4
      billion in 2014 dollars.

PMID- 29059336
TI  - Friday Music With Paul.

PMID- 29059337
TI  - Understanding personal risk of oropharyngeal cancer: risk-groups for oncogenic
      oral HPV infection and oropharyngeal cancer.
AB  - Background: Incidence of human papillomavirus (HPV)-related oropharyngeal cancer
      is increasing. There is interest in identifying healthy individuals most at risk
      for development of oropharyngeal cancer to inform screening strategies. Patients
      and methods: All data are from 2009 to 2014, including 13 089 people ages 20-69
      in the National Health and Nutrition Examination Survey (NHANES), oropharyngeal
      cancer cases from the Surveillance, Epidemiology, and End Results (SEER 18)
      registries (representing ~28% of the US population), and oropharyngeal cancer
      mortality from National Center for Health Statistics (NCHS). Primary study
      outcomes are (i) prevalence of oncogenic HPV DNA in an oral rinse and gargle
      sample, and (ii) incident oropharyngeal squamous cell cancer. Results: Oncogenic
      oral HPV DNA is detected in 3.5% of all adults age 20-69 years; however, the
      lifetime risk of oropharyngeal cancer is low (37 per 10 000). Among men 50-59
      years old, 8.1% have an oncogenic oral HPV infection, 2.1% have an oral HPV16
      infection, yet only 0.7% will 'ever' develop oropharyngeal cancer in their
      lifetime. Oncogenic oral HPV prevalence was higher in men than women, and
      increased with number of lifetime oral sexual partners and tobacco use. Men who
      currently smoked and had >=5 lifetime oral sexual partners had 'elevated risk'
      (prevalence = 14.9%). Men with only one of these risk factors (i.e. either smoked
      and had 2-4 partners or did not smoke and had >=5 partners) had 'medium risk'
      (7.3%). Regardless of what other risk factors participants had, oncogenic oral
      HPV prevalence was 'low' among those with only <=1 lifetime oral sexual partner
      (women = 0.7% and men = 1.7%). Conclusions: Screening based upon oncogenic oral
      HPV detection would be challenging. Most groups have low oncogenic oral HPV
      prevalence. In addition to the large numbers of individuals who would need to be
      screened to identify prevalent oncogenic oral HPV, the lifetime risk of
      developing oropharyngeal caner among those with infection remains low.

PMID- 29059338
TI  - Burden of Tobacco in Pakistan: Findings From Global Adult Tobacco Survey 2014.
AB  - Introduction: The Global Adult Tobacco Survey (GATS) is the global standard for
      systematically monitoring adult tobacco use and tracking key tobacco control
      indicators. Methods: Using a multistage stratified cluster design, 9856
      households were sampled, and one individual was randomly selected from each
      household. Standard GATS questionnaire was used to collect information on tobacco
      use, cessation, second-hand smoke, knowledge, attitudes, and perceptions. Data
      were analyzed per standard GATS protocol. Results: Of 9856 individuals, 7831
      individuals completed the interview. The response rate was 81%. Overall, 19.1%
      adults were currently using tobacco products and among them, 12.4% smoked
      tobacco, and 7.7% smokeless tobacco. Exposure to second-hand smoke was seen in
      86% in a restaurant while it was 76% on public transportation. A total of 24.7%
      smokers made a quit attempt in the past 12 months. Anticigarette smoking
      information was observed by 37.7% adults, while 29.7% current smokers thought
      about quitting after reading health warning labels on cigarette packages. Most
      (85%) adults favored no smoking in public places, and 74.8% favored increasing
      taxes on tobacco products. Current cigarette smokers spent Pakistani Rupees 767.3
      per month (7.78 USD) on manufactured cigarettes and consumed 4500 cigarette
      sticks (225 packs) annually. Conclusions: Besides 19.1% tobacco users, the
      majority (86%) were exposed to second-hand smoke at public places indicating that
      ban on tobacco use in public places is not being followed. A quarter of current
      smokers wants to quit smoking who may be provided assistance to reduce tobacco
      burden. Implications: This study provides national-level data about tobacco use
      and its burden and also indicates weak implantation of tobacco control laws.
      There is need to devise a strategy for proper implementation of these laws to
      reduce the tobacco burden in the country.

PMID- 29059339
TI  - The Association Between State Value-Added Taxes and Tobacco Use in India-Evidence
      From GATS and TCP India Survey.
AB  - Introduction: State value-added taxes (VAT) on tobacco products have been
      increased significantly in recent years in India. Evidence on how these VATs were
      associated with smoking is highly needed. Methods: State bidi and cigarette VAT
      rates were linked to Global Adult Tobacco Survey (GATS) India 2009-2010 and
      Tobacco Control Policy (TCP) India Survey waves 1 (2010-2011) and 2 (2012-2013),
      respectively. These linked data were used to analyze the associations between
      bidi VAT rates and bidi smoking, between cigarette VAT rates and cigarette
      smoking, and between the two VAT rates and dual use of bidis and cigarettes.
      Weighted logistic regressions were employed to examine GATS cross-sectional data,
      whereas generalized estimating equations (GEE) were employed to examine
      longitudinal TCP data. We further stratified the analyses by gender. Results: A
      10% increase in cigarette VAT rates was associated with a 6.5% (p < .001)
      decrease in dual use of cigarettes and bidis among adults and a 0.9% decrease (p
      < .05) in cigarette smoking among males in TCP; and with a 21.6% decrease (p <
      .05) in dual use among adults and a 17.2% decrease (p < .001) in cigarette
      smoking among males in GATS. TCP analyses controlling for state fixed effects are
      less likely to be biased and indicate a cigarette price elasticity of -0.44. As
      female smoking prevalence was extremely low, these associations were
      nonsignificant for females. Conclusions: Higher state cigarette VAT rates in
      India were significantly associated with lower cigarette smoking and lower dual
      use of cigarettes and bidis. Increasing state VAT rates may significantly reduce
      smoking in India. Implications: Both Global Adult Tobacco Survey and Tobacco
      Control Policy (TCP) India datasets suggest that higher state cigarette value
      added tax rates were significantly associated with lower male cigarette smoking
      and lower dual use of cigarettes and bidis among all adults in India. TCP
      analyses indicate a cigarette price elasticity of -0.44. As shown in this study,
      state tobacco taxes in the current taxation system are likely effective in
      reducing smoking. Given this, a future central goods and service tax (GST) system
      could consider keeping states' authority in implementing local tobacco taxes or
      designing a GST system that is equally or more effective in reducing tobacco use.

PMID- 29059340
TI  - Trajectories of Responses to Pictorial Cigarette Pack Warnings.
AB  - Background: Pictorial warnings on cigarette packs are a cost-effective policy
      level intervention for smoking cessation; however, little research has examined
      changes in the impact of warnings over time, especially shortly following the
      first exposure to pictorial warnings. We sought to characterize the trajectories
      of responses to pictorial cigarette pack warnings soon after first exposure.
      Methods: Participants were 2149 adult smokers in North Carolina and California,
      United States. In 2014-2015, we randomized smokers to have pictorial
      (intervention) or text-only (control) warnings on their cigarette packs for 4
      weeks. Weekly surveys assessed psychosocial and behavioral outcomes. Results:
      After 1 week, smokers in the intervention arm reported higher levels of most
      outcomes, compared with the control arm. Over subsequent weeks, smokers in both
      trial arms had decreases in thinking about the harms of smoking (beta = -0.046),
      positive (beta = -0.036), and negative (beta = -0.042) smoking reinforcement
      attitudes, and increases in quit intentions (beta = 0.070) and cigarette forgoing
      (beta = 0.137) (all p < .05). Only negative affective reactions decreased more in
      the intervention versus control condition (pinteraction < .01). Conclusions: The
      impact of pictorial cigarette pack warnings on emotions and cognitions may wane
      over time. In contrast, quit intentions and cigarette forgoing may continue to
      increase, at least during the initial period after introduction. Rotation of
      pictorial warnings may help prevent warning wear-out. Implications: Cigarette
      smoking is the leading cause of preventable morbidity and mortality and warnings
      on cigarette packs are a cost-effective policy-level intervention. Prior studies
      reporting on cigarette pack warning "wear out" have been limited by being short
      term single-session experimental studies. Ours are the first study to
      experimentally examine the trajectories of several outcomes after first exposure
      and report that the impact of pictorial cigarette pack warnings on emotions and
      cognitions may wane over time while quit intentions and cigarette forgoing may
      continue to increase. Trials Registration: ClinicalTrials.gov identifier:
      NCT02247908; https://clinicaltrials.gov/ct2/show/NCT02247908.

PMID- 29059341
TI  - The Relationship of E-Cigarette Use to Cigarette Quit Attempts and Cessation:
      Insights From a Large, Nationally Representative U.S. Survey.
AB  - Objectives: While cessation from cigarettes is a top priority for public health,
      controversy surrounds the role of e-cigarettes for quitting cigarettes. This
      study examines the role of e-cigarettes in quit attempts and 3-month cigarette
      abstinence using a large, recent nationally representative US sample. Methods:
      Data from the 2014/15 Tobacco Use Supplement-Current Population Survey (TUS-CPS)
      on cigarette and e-cigarette use and individual characteristics were supplemented
      with information on state tobacco control policies. We estimated frequencies and
      multivariate logistic equations for making a quit attempt among those who smoked
      1 year earlier and for remaining abstinent at least 3 months among those making a
      quit attempt. These two outcomes were related to demographic characteristics,
      tobacco control policies and different frequency measures of e-cigarette use
      (ever, at least 1, 5, 20 of the last 30 days, a continuous measure of days use).
      Results: Having made a quit attempt was more likely among smokers using e
      cigarettes than non-users. Among those making at least one quit attempt, quit
      success was lower among ever users, but higher among those with at least 5 days
      use of e-cigarettes in the last month. Both quit attempts and quit success were
      linearly related to the frequency of e-cigarette use. Conclusions: Consistent
      with randomized trials and those observational studies that measure frequency of
      e-cigarette use, both quit attempts and quit success were positively associated
      with increased frequency of e-cigarette use. Frequency of e-cigarette use was
      important in gauging the nature of these relationships. Implications: Previous
      studies have obtained mixed results regarding the relationship of e-cigarette use
      to cigarette smoking cessation. This study provides a more precise methodology
      for considering the relationship of e-cigarette use to quit attempts and to quit
      success, and finds that quit attempts and quit success increase with the number
      of days use in the past month.

PMID- 29059342
TI  - Mathematical model of calcium exchange during haemodialysis using a citrate
      containing dialysate.
AB  - Calcium has two important roles in haemodialysis. It participates in the
      activation of blood coagulation and calcium intakes have a major impact on
      patient mineral and bone metabolism. The aim of this article is to propose a
      mathematical model for calcium ions concentration in a dialyzer during
      haemodialysis using a citrate dialysate. The model is composed of two elements.
      The first describes the flows of blood and dialysate in a dialyzer fibre. It was
      obtained by asymptotic analysis and takes into account the anisotropy of the
      fibres forming a dialyzer. Newtonian and non-Newtonian blood rheologies were
      tested. The second part of the model predicts the evolution of the concentration
      of five chemical species present in these fluids. The fluid velocity field drives
      the convective part of a convection-reaction-diffusion system that models the
      exchange of free and complexed calcium. We performed several numerical
      experiments to calculate the free calcium concentration in the blood in a
      dialyzer using dialysates with or without citrate. The choice of blood rheology
      had little effect on the fluid velocity field. Our model predicts that only a
      citrate based dialysate without calcium can decrease free calcium concentration
      at the blood membrane interface low enough to inhibit blood coagulation. Moreover
      for a given calcium dialysate concentration, adding citrate to the dialysate
      decreases total calcium concentration in the blood at the dialyzer outlet. This
      decrease of the calcium concentration can be compensated by infusing in the
      dialyzed blood a quantity of calcium computed from the model.

PMID- 29059343
TI  - Arrhythmogenic right ventricular cardiomyopathy vs. dilated cardiomyopathy:
      implications for next-generation sequencing and microRNA regulation in
      appropriate diagnosis-Authors' reply.

PMID- 29059344
TI  - A Qualitative Evaluation of Mental Health Clinic Staff Perceptions of Barriers
      and Facilitators to Treating Tobacco Use.
AB  - Introduction: Veterans with mental health disorders smoke at high rates, but
      encounter low rates of tobacco treatment. We sought to understand barriers and
      facilitators to treating tobacco use in VA mental health clinics. Methods: This
      qualitative study was part of a trial evaluating a telephone care coordination
      program for smokers using mental health services at six VA facilities. We
      conducted semi-structured interviews with 14 staff: 12 mental health clinic staff
      working at the parent study's intervention sites (n = 6 psychiatrists, three
      psychologists, two social workers, one NP), as well as one psychiatrist and one
      psychologist on the VA's national tobacco advisory committee. Interviews were
      transcribed and inductively coded to identify themes. Results: Five "barriers"
      themes emerged: (1) competing priorities, (2) patient challenges/resistance, (3)
      complex staffing/challenging cross-discipline coordination, (4) mixed perceptions
      about whether tobacco is a mental health care responsibility, and (5) limited
      staff training/comfort in treating tobacco. Five "facilitators" themes emerged:
      (1) reminding mental health staff about tobacco, (2) staff belief in the
      importance of addressing tobacco, (3) designating a cessation medication
      prescriber, (4) linking tobacco to mental health outcomes and norms, and (5)
      limiting mental health staff burden. Conclusions: VA mental health staff struggle
      with knowing that tobacco use is important, but they face competing priorities,
      encounter patient resistance, are conflicted on their role in addressing tobacco,
      and lack tobacco training. They suggested strategies at multiple levels that
      would help overcome those barriers that can be used to design interventions that
      improve tobacco treatment delivery for mental health patients. Implications: This
      study builds upon the existing literature on the high rates of smoking, but low
      rates of treatment, in people with mental health diagnoses. This study is one of
      the few qualitative evaluations of mental health clinic staff perceptions of
      barriers and facilitators to treating tobacco. The study results provide a multi
      level framework for developing strategies to improve the implementation of
      tobacco treatment programs in mental health clinics.

PMID- 29059345
TI  - State Tobacco Policies as Predictors of Evidence-Based Cessation Method Usage:
      Results From a Large, Nationally Representative Dataset.
AB  - Introduction: Evidence-based cessation methods including nicotine replacement
      therapy (NRT), non-NRT medications, quitlines, and behavioral treatments are
      underutilized by smokers attempting to quit. Although a number of studies have
      demonstrated a relationship between state-level tobacco policies (eg, taxation,
      appropriations) and cessation, whether such state-level factors influence
      likelihood of using an evidence-based treatment is unclear. Accordingly, the aims
      of the present study were: (1) to describe evidence-based cessation method
      utilization by state and (2) to examine the effect of state-level factors on
      cessation method utilization above and beyond individual-level predictors.
      Methods: Data were utilized from the 2010-2011 Tobacco Use Supplement to the
      Current Population Survey (TUS-CPS). Participants included 9232 smokers who
      reported a past-year quit attempt. Data on 11 state-level predictors were
      collated from national datasets. Analyses were based on: (1) descriptive
      characterization of quit method usage, (2) logistic regression models to
      determine state-level factors as predictors of quit method utilization,
      controlling for individual-level predictors, (3) cluster analyses grouping states
      with similar state-level factors, and (4) examination of cluster as a predictor
      of cessation method. Results: Tobacco control appropriations significantly
      predicted NRT, quitline, and behavioral treatment utilization. Additional state
      level factors that demonstrated significant relationships included Medicaid
      coverage of non-NRT medications and behavioral treatment, tobacco tax rate,
      smoking prevalence, and percentage of population uninsured. State clustering
      significantly predicted quit method across all four methods. Conclusions: State
      level factors influence the likelihood of residents utilizing evidence-based quit
      methods. Results are discussed in terms of implications for tobacco policy at the
      state level. Implications: Results from the present study highlight state tobacco
      control appropriations as a robust predictor of evidence-based cessation method
      utilization. Other significant state-level predictors of evidence-based cessation
      method utilization included Medicaid coverage of non-NRT medications and
      behavioral treatment, tobacco tax rate, smoking prevalence, and percentage of
      population uninsured. Moreover, state-level predictors clustered together to
      significantly predict evidence-based cessation method utilization. Thus,
      increasing tobacco control appropriations, extending health insurance coverage,
      maximizing revenue from tobacco taxation and tobacco settlements, and ultimately
      decreasing smoking prevalence are important targets for individual states to
      promote utilization of evidence-based cessation methods.

PMID- 29059346
TI  - Regiospecific Acetylation of Xylan is Mediated by a Group of DUF231-Containing O
      Acetyltransferases.
AB  - Xylan is a major hemicellulose in the secondary walls of vessels and fibers, and
      its acetylation is essential for normal secondary wall assembly and properties.
      The acetylation of xylan can occur at multiple positions of its backbone xylosyl
      residues, including 2-O-monoacetylation, 3-O-monoacetylation, 2,3-di-O
      acetylation and 3-O-acetylation of 2-O-glucuronic acid (GlcA)-substituted xylosyl
      residues, but the biochemical mechanism controlling the regiospecific acetylation
      of xylan is largely unknown. Here, we present biochemical characterization of a
      group of Arabidopsis thaliana DUF231-containing proteins, namely TBL28,
      ESK1/TBL29, TBL30, TBL3, TBL31, TBL32, TBL33, TBL34 and TBL35, for their roles in
      catalyzing the regiospecific acetylation of xylan. Acetyltransferase activity
      assay of recombinant proteins demonstrated that all of these proteins possessed
      xylan acetyltransferase activities catalyzing the transfer of acetyl groups from
      acetyl-CoA onto xylooligomer acceptors albeit with differential specificities.
      Structural analysis of their reaction products revealed that TBL28, ESK1, TBL3,
      TBL31 and TBL34 catalyzed xylan 2-O- and 3-O-monoacetylation and 2,3-di-O
      acetylation with differential positional preference, TBL30 carried out 2-O- and 3
      O-monoacetylation, TBL35 catalyzed 2,3-di-O-acetylation, and TBL32 and TBL33
      mediated 3-O-acetylation of 2-O-GlcA-substituted xylosyl residues. Furthermore,
      mutations of the conserved GDS and DXXH motifs in ESK1 were found to result in a
      complete loss of its acetyltransferase activity. Together, these results
      establish that these nine DUF231-containing proteins are xylan acetyltransferases
      mediating the regiospecific acetylation of xylan and that the conserved GDS and
      DXXH motifs are critical for their acetyltransferase activity.

PMID- 29059348
TI  - Understanding differences in cervical cancer incidence in Western Europe:
      comparing Portugal and England.
AB  - Background: Cervical cancer incidence has decreased over time in England
      particularly after the introduction of organized screening. In Portugal, where
      opportunistic screening has been widely available with only slightly lower
      coverage than that of the organized programme in England, rates of cervical
      cancer have been higher than in England. We compared the burden of cervical
      cancer, risk factors and preventive interventions over time in both countries, to
      identify elements hindering the further decline in incidence and mortality in
      Portugal. Methods: We used joinpoint regression to identify significant changes
      in rate time-trends. We also analyzed individual-level Portuguese data on sexual
      behaviour and human papillomavirus prevalence, and recent aggregate data on
      organized and opportunistic screening coverage. We compared published estimates
      of survival, risk factors and historical screening coverage for both countries.
      Results: Despite stable incidence, cervical cancer mortality has declined in both
      countries in the last decade. The burden has been 4 cases and 1 death per 100 000
      women annually higher in Portugal than in England. Differences in human
      papillomavirus prevalence and risk factors for infection and disease progression
      do not explain the difference found in cervical cancer incidence. Significant
      mortality declines in both countries followed the introduction of different
      screening policies, although England showed a greater decline than Portugal over
      nearly 2 decades after centralizing organized screening. Conclusion: The higher
      rates of cervical cancer in Portugal compared to England can be explained by
      differences in screening quality and coverage.

PMID- 29059349
TI  - Using Elastic Net Penalized Cox Proportional Hazards Regression to Identify
      Predictors of Imminent Smoking Lapse.
AB  - Introduction: Machine learning algorithms such as elastic net regression and
      backwards selection provide a unique and powerful approach to model building
      given a set of psychosocial predictors of smoking lapse measured repeatedly via
      ecological momentary assessment (EMA). Understanding these predictors may aid in
      developing interventions for smoking lapse prevention. Methods: In a randomized
      controlled smoking cessation trial, smartphone-based EMAs were collected from 92
      participants following a scheduled quit date. This secondary analysis utilized
      elastic net penalized cox proportional hazards regression and model approximation
      via backward elimination to (a) optimize a predictive model of time to first
      lapse and (b) simplify that model to its core constituent predictors to maximize
      parsimony and generalizability. Results: Elastic net proportional hazards
      regression selected 17 of 26 possible predictors from 2065 EMAs to model time to
      first lapse. The predictors with the highest magnitude regression coefficients
      were having consumed alcohol in the past hour, being around and interacting with
      a smoker, and having cigarettes easily available. This model was reduced using
      backward elimination, retaining five predictors and approximating to 93.9% of
      model fit. The retained predictors included those mentioned above as well as
      feeling irritable and being in areas where smoking is either discouraged or
      allowed (as opposed to not permitted). Conclusions: The strongest predictors of
      smoking lapse were environmental in nature (e.g., being in smoking-permitted
      areas) as opposed to internal factors such as psychological affect. Interventions
      may be improved by a renewed focus of interventions on these predictors.
      IMPLICATIONS: The present study demonstrated the utility of machine learning
      algorithms to optimize the prediction of time to smoking lapse using EMA data.
      The two models generated by the present analysis found that environmental factors
      were most strongly related to smoking lapse. The results support the use of
      machine learning algorithms to investigate intensive longitudinal data, and
      provide a foundation for the development of highly tailored, just-in-time
      interventions that can target upon multiple antecedents of smoking lapse.

PMID- 29059350
TI  - Smoking Among Hispanic/Latino Nationality Groups and Whites, Comparisons Between
      California and the United States.
AB  - Introduction: Although California is home to the largest Hispanic/Latino
      population, few studies have compared smoking behavior trends of Hispanic/Latino
      nationality groups in California to the remaining United States, which may
      identify the impact of the states antitobacco efforts on these groups. This study
      compared smoking status, frequency, and intensity among Mexican Americans,
      Central/South Americans, and non-Hispanic Whites in California to the remaining
      United States in the 1990s and 2000s. Methods: Data were analyzed using the 1992
      2011 Current Population Survey Tobacco Use Supplement to report the estimated
      prevalence of smoking status, frequency, and intensity by decade, race/ethnicity,
      and state residence. Weighted logistic regression explored sociodemographic
      factors associated with never and heavy smoking (>=20 cigarettes per day).
      Results: There were absolute overall increases from 6.8% to 9.6% in never smoking
      across all groups. Compared to the remaining United States, there was a greater
      decrease in heavy smoking among Mexican American current smokers in California
      (5.1%) and a greater increase in light and intermittent smokers among
      Central/South American current smokers in California (9.3%) between decades.
      Compared to those living in the remaining United States, smokers living in
      California had lower odds of heavy smoking (1990s: odds ratio [OR] = 0.64, 95%
      confidence interval [CI] = 0.62, 0.66; 2000s: 0.54, 95% CI = 0.52, 0.55).
      Conclusions: California state residence significantly impacted smoking behaviors
      as indicated by significant differences in smoking intensity between California
      and the remaining United States among Hispanic/Latino nationality groups.
      Understanding smoking behaviors across Hispanic/Latino nationality groups in
      California and the United States can inform tobacco control and smoking
      prevention strategies for these groups. Implications: The present study explored
      the differences in smoking behaviors between Whites, Mexican Americans, and
      Central South/Americans living in California versus the rest of the United States
      in the 1990s and the 2000s. The results contribute to our current knowledge as
      there have been minimal efforts to provide disaggregated cigarette consumption
      information among Hispanic/Latino nationality groups. Additionally, by comparing
      cigarette consumption between those in California and the remaining United
      States, our data may provide insight into the impact of California's antitobacco
      efforts in reaching Hispanic/Latino subpopulations relative to the remaining US
      states, many of which have had less tobacco control policy implementation.

PMID- 29059347
TI  - Sim1 Neurons Are Sufficient for MC4R-Mediated Sexual Function in Male Mice.
AB  - Sexual dysfunction is a poorly understood condition that affects up to one-third
      of men around the world. Existing treatments that target the periphery do not
      work for all men. Previous studies have shown that central melanocortins, which
      are released by pro-opiomelanocortin neurons in the arcuate nucleus of the
      hypothalamus, can lead to male erection and increased libido. Several studies
      specifically implicate the melanocortin 4 receptor (MC4R) in the central control
      of sexual function, but the specific neural circuitry involved is unknown. We
      hypothesized that single-minded homolog 1 (Sim1) neurons play an important role
      in the melanocortin-mediated regulation of male sexual behavior. To test this
      hypothesis, we examined the sexual behavior of mice expressing MC4R only on Sim1
      positive neurons (tbMC4Rsim1 mice) in comparison with tbMC4R null mice and wild
      type controls. In tbMC4Rsim1 mice, MC4R reexpression was found in the medial
      amygdala and paraventricular nucleus of the hypothalamus. These mice were paired
      with sexually experienced females, and their sexual function and behavior was
      scored based on mounting, intromission, and ejaculation. tbMC4R null mice showed
      a longer latency to mount, a reduced intromission efficiency, and an inability to
      reach ejaculation. Expression of MC4R only on Sim1 neurons reversed the sexual
      deficits seen in tbMC4R null mice. This study implicates melanocortin signaling
      via the MC4R on Sim1 neurons in the central control of male sexual behavior.

PMID- 29059351
TI  - Differences in Subjective Experiences to First Use of Menthol and Nonmenthol
      Cigarettes in a National Sample of Young Adult Cigarette Smokers.
AB  - Purpose: Menthol has been hypothesized to ease the harshness of cigarette smoke.
      Thus, sensory experiences at first cigarette use may be one mechanism by which
      menthol facilitates progression to regular smoking. This study examined
      differences in subjective experiences to the first use of a menthol versus
      nonmenthol cigarette among new young adult smokers. Methods: Data were drawn from
      waves 5-8 of the Truth Initiative Young Adult Cohort Study, a national sample of
      18-34 year olds assessed every 6 months. Analyses included a subset of young
      adult current smokers (n = 251) who initiated smoking in the past 6 months.
      Subjective responses to first cigarette use were assessed across menthol and
      nonmenthol initiators in bivariate analyses and adjusted models controlling for
      smoking correlates. Results: Fifty-two percent of new young adult smokers used a
      menthol cigarette at first use. First use of a menthol cigarette was higher in
      those aged 18-24 (vs. 25-34). Most black smokers (93.1%) were menthol initiators
      compared to 43.9% of white smokers. More than half of menthol and nonmenthol
      initiates felt relaxed or calm, dizzy, lightheaded, liking the taste and a rush
      or buzz at first use. Menthol initiators were less likely in bivariate and
      multivariable analyses to experience feeling nauseated at first use (adjusted
      odds ratio = 0.45; p = .020) compared to nonmenthol initiators. Conclusions:
      While few differences were found between menthol and nonmenthol initiators in
      their subjective experiences, fewer menthol initiates felt nauseated at first
      cigarette use. Future research needs to identify additional mechanisms linking
      menthol initiation to smoking progression. Implications: Menthol initiators were
      more likely to be younger (18-24 vs. 25-34), and black (vs. white) compared to
      nonmenthol initiators. Our finding that menthol initiators were less likely to
      feel nauseated at first cigarette use compared to nonmenthol initiators suggests
      that menthol may reduce aversion to early cigarette use among young smokers and
      thus has the potential to facilitate continued experimentation. Interventions and
      policy approaches to reduce tobacco use initiation and progression are urgently
      needed in young people.

PMID- 29059353
TI  - Leucocyte immunoglobulin-like receptor subfamily-B5 (LILRB5) genetic variation
      and statin-associated muscle symptoms: another piece in a puzzling puzzle.

PMID- 29059352
TI  - Believability of Cigarette Warnings About Addiction: National Experiments of
      Adolescents and Adults.
AB  - Introduction: We conducted two experiments to examine the believability of three
      addiction-focused cigarette warnings and the influence of message source on
      believability among adolescents and adults in the United States. Methods:
      Experimental data were collected using national phone surveys of adolescents (age
      13-17; n = 1125; response rate, 66%) and adults (age 18+; n = 5014; response
      rate, 42%). We assessed the believability of three cigarette warnings about
      addiction attributed to four message sources (Food and Drug Administration [FDA],
      Surgeon General, Centers for Disease Control and Prevention [CDC], no source).
      Results: The majority of adolescents and adults reported the three cigarette
      warnings were very believable (49%-81% for adolescents; 47%-76% for adults). We
      found four to five times higher odds of adolescents believing a warning that
      cigarettes are addictive (warning 1) or that nicotine was an addictive chemical
      (warning 2) compared to a warning that differentiated the addictive risks of
      menthol versus traditional cigarettes (warning 3), warning 1 adjusted odds ratio
      (aOR): 4.53, 95% confidence interval (CI): 3.10, 6.63; warning 2 aOR: 3.87, 95%
      CI: 2.70, 5.50. Similarly, we found three to five times higher odds of adults
      (including current smokers) believing the same warnings, warning 1 aOR: 3.74, 95%
      CI: 2.82, 4.95; warning 2 aOR: 3.24, 95% CI: 2.45, 4.28. Message source had no
      overall impact on the believability of warnings for either population.
      Conclusions: Our findings support the implementation of FDA's required warnings
      that cigarettes are addictive and that nicotine is an addictive chemical. These
      believable warnings may deter adolescents from initiating smoking and encourage
      adults to quit smoking. Implications: This article describes, for the first time,
      the believability of different cigarette warnings about addiction. We now know
      that the majority of adolescents and adults believe cigarette warnings that
      highlight cigarettes as addictive and that nicotine is an addictive chemical in
      tobacco. However, a warning that highlighted the relative risk of addiction for
      menthol cigarettes compared to traditional cigarettes was not as believable among
      either population. Our findings support the implementation of FDA's required
      warnings that cigarettes are addictive and that nicotine is an addictive chemical
      that may deter adolescents from initiating smoking and encourage adults to quit
      smoking.

PMID- 29059354
TI  - Inflammation and Fibrosis in Perirenal Adipose Tissue of Patients With
      Aldosterone-Producing Adenoma.
AB  - The prevalence of primary aldosteronism is much higher than previously thought.
      Recent studies have shown that primary aldosteronism is related to a higher risk
      of cardiovascular events. However, the underlying mechanism is not yet clear.
      Here we investigate the characteristics, including inflammation, fibrosis, and
      adipokine expression, of adipose tissues from different deposits in patients with
      aldosterone-producing adenoma (APA). Inflammation and fibrosis changes were
      evaluated in perirenal and subcutaneous adipose tissues obtained from patients
      with APA (n = 16), normotension (NT; n = 10), and essential hypertension (EH; n =
      5) undergoing laparoscopic surgery. We also evaluated the effect of aldosterone
      in isolated human perirenal adipose tissue stromal vascular fraction (SVF) cells
      and investigated the effect of aldosterone in mouse 3T3-L1 and brown
      preadipocytes. Compared with the EH group, significantly higher levels of
      interleukin-6 (IL-6) and tumor necrosis factor-alpha messenger RNA (mRNA) and
      protein were observed in perirenal adipose tissue of patients with APA.
      Expression of genes related to fibrosis and adipogenesis in perirenal adipose
      tissue was notably higher in patients with APA than in patients with NT and EH.
      Aldosterone significantly induced IL-6 and fibrosis gene mRNA expression in
      differentiated SVF cells. Aldosterone treatment enhanced mRNA expression of genes
      associated with inflammation and fibrosis and stimulated differentiation of 3T3
      L1 and brown preadipocytes. In conclusion, these data indicate that high
      aldosterone in patients with APA may induce perirenal adipose tissue dysfunction
      and lead to inflammation and fibrosis, which may be involved in the high risk of
      cardiovascular events observed in patients with primary aldosteronism.

PMID- 29059355
TI  - Smokers' Understandings of Addiction to Nicotine and Tobacco: A Systematic Review
      and Interpretive Synthesis of Quantitative and Qualitative Research.
AB  - Background: Despite the centrality of addiction in academic accounts of smoking,
      there is little research on smokers' beliefs about addiction to smoking, and the
      role of nicotine in tobacco dependence. Smokers' perspectives on nicotine's role
      in addiction are important given the increasing prevalence of nontobacco nicotine
      products such as e-cigarettes. We conducted a systematic review of studies
      investigating smokers' understandings and lay beliefs about addiction to smoking
      and nicotine. Method: We searched PubMed, Embase, CINAHL, and PsycINFO for
      studies investigating lay beliefs about addiction to smoking. Twenty-two
      quantitative and 24 qualitative studies met inclusion criteria. Critical
      interpretive synthesis was used to analyze the results. Results: Very few studies
      asked about addiction to nicotine. Quantitative studies that asked about
      addiction to smoking showed that most smokers believe that cigarettes are an
      addictive product, and that they are addicted to smoking. Across qualitative
      studies, nicotine was not often mentioned by participants. Addiction to smoking
      was most often characterized as a feeling of "need" for cigarettes resulting from
      an interplay between physical, mental, and social processes. Overall, we found
      that understandings of smoking were more consistent with the biopsychosocial
      model of addiction than with more recent models that emphasize the biological
      aspects of addiction. Conclusion: Researchers should not treat perceptions of
      addiction to smoking interchangeably with perceptions of addiction to nicotine.
      More research on lay beliefs about nicotine is required, particularly considering
      the increasing use of e-cigarettes and their potential for long-term nicotine
      maintenance for harm reduction. Implications: Quantitative studies show that most
      smokers believe that smoking is addictive and that they are addicted. A feeling
      of "need" for cigarettes was central to qualitative accounts of addiction, but
      nicotine was not often discussed. Overall, smokers' understandings of addiction
      reflect a biopsychosocial model rather than a neurobiological one. Given the
      growing market for e-cigarettes and therapeutic nicotine, more research is
      required on lay beliefs about nicotine and addiction.

PMID- 29059356
TI  - Implementing an Evidence-based Tobacco Control Program at Five 2-1-1 Call
      Centers: An Evaluation Using the Consolidated Framework for Implementation
      Research.
AB  - Introduction: The Smoke-Free Homes Program (SFH) is an evidence-based
      intervention offered within 2-1-1 information and referral call centers to
      promote smoke-free homes in low-income populations. We used the Consolidated
      Framework for Implementation Research to conduct a mixed-methods analysis of
      facilitators and barriers to scaling up SFH to five 2-1-1 sites in the United
      States. Methods: Data were collected from staff in 2015-2016 via online surveys
      administered before (N = 120) and after SFH training (N = 101) and after SFH
      implementation (N = 79). Semi-structured telephone interviews were conducted in
      2016 with 25 staff to examine attitudes towards SFH, ways local context affected
      implementation, and unintended benefits and consequences of implementing SFH.
      Results: Post-implementation, 79% of respondents reported SFH was consistent with
      their 2-1-1's mission, 70% thought it led to more smoke-free homes in their
      population, 62% thought it was easy to adapt, and 56% thought participants were
      satisfied. Composite measures of perceived appropriateness of SFH for 2-1-1
      callers and staff positivity toward SFH were significantly lower post
      implementation than pre-implementation. In interviews, staff said SFH fit with
      their 2-1-1's mission but expressed concerns about intervention sustainability,
      time and resources needed for delivery, and how SFH fit into their workflow.
      Conclusions: Sites' SFH implementation experiences were affected both by demands
      of intervention delivery and by SFH's perceived effectiveness and fit with
      organizational mission. Future implementation of SFH and other tobacco control
      programs should address identified barriers by securing ongoing funding,
      providing dedicated staff time, and ensuring programs fit with staff workflow.
      Implications: Smoke-free homes policies reduce exposure to second-hand smoke.
      Partnering with social service agencies offers a promising way to scale up
      evidence-based smoke-free homes interventions among low-income populations. We
      found that the SFH intervention was acceptable and feasible among multiple 2-1-1
      delivery sites. There were also significant challenges to implementation,
      including site workflow, desire to adapt the intervention, time needed for
      intervention delivery, and financial sustainability. Addressing such challenges
      will aid future efforts to scale up evidence-based tobacco control interventions
      to social service agencies such as 2-1-1.

PMID- 29059357
TI  - Combined off-pump minimally invasive coronary artery bypass grafting and mitral
      valve repair with NeoChord via a left anterolateral small thoracotomy.
AB  - Off-pump direct coronary artery bypass grafting through a left anterior small
      thoracotomy is widely utilized for minimally invasive myocardial
      revascularization. More recently, a novel technique for transapical off-pump
      mitral valve repair with the NeoChord device is demonstrating its efficacy. This
      report describes a case of an 84-year-old male patient with coronary artery
      disease involving the left anterior descending coronary artery and acute severe
      mitral regurgitation secondary to posterior leaflet flail who underwent both off
      pump coronary artery bypass and mitral valve repair with the transapical
      implantation of artificial chordae using the NeoChord DS 1000 system through the
      same anterolateral small thoracotomy.

PMID- 29059358
TI  - Daptomycin.
AB  - Daptomycin is a cyclic lipopeptide antibiotic used for the treatment of Gram
      positive infections including complicated skin and skin structure infections,
      right-sided infective endocarditis, bacteraemia, meningitis, sepsis and urinary
      tract infections. Daptomycin has distinct mechanisms of action, disrupting
      multiple aspects of cell membrane function and inhibiting protein, DNA and RNA
      synthesis. Although daptomycin resistance in Gram-positive bacteria is uncommon,
      there are increasing reports of daptomycin resistance in Staphylococcus aureus,
      Enterococcus faecium and Enterococcus faecalis. Such resistance is seen largely
      in the context of prolonged treatment courses and infections with high bacterial
      burdens, but may occur in the absence of prior daptomycin exposure. Furthermore,
      use of inadequate treatment regimens, irregular drug supply and poor drug quality
      have also been recognized as other important risk factors for emergence of
      daptomycin-resistant strains. Antimicrobial susceptibility testing of Gram
      positive bacteria, communication between clinicians and laboratories,
      establishment of internet-based reporting systems, development of better and more
      rapid diagnostic methods and continuous monitoring of drug resistance are urgent
      priorities.

PMID- 29059359
TI  - Cigarette constituent health communications for smokers: impact of chemical,
      imagery, and source.
AB  - Introduction: Communication campaigns are incorporating tobacco constituent
      messaging to reach smokers, yet there is a dearth of research on how such
      messages should be constructed or will be received by smokers. Methods: In a
      2x2x2 experiment, we manipulated three cigarette constituent message components:
      (1) the toxic constituent of tobacco (arsenic vs. lead) with a corresponding
      health effect, (2) the presence or absence of an evocative image, and (3) the
      source of the message (FDA vs. no source). We recruited smokers (N = 1,669, 55.4%
      women) via an online platform and randomized them to 1 of the 8 message
      conditions. Participants viewed the message and rated its believability and
      perceived effectiveness, the credibility of the message source, and action
      expectancies (i.e., likelihood of seeking additional information and help with
      quitting as a result of seeing the message). Results: We found significant main
      effects of image, constituent, and source on outcomes. The use of arsenic as the
      constituent, the presence of an evocative image, and the FDA as the source
      increased the believability, source credibility, and perceived effectiveness of
      the tobacco constituent health message. Conclusions: Multiple elements of a
      constituent message, including type of constituent, imagery, and message source,
      impact their reception among smokers. Specifically, communication campaigns
      targeting smokers that utilize arsenic as the tobacco constituent, visual
      imagery, and the FDA logo may be particularly effective in changing key outcomes
      that are associated with subsequent attitude and behavioral changes.
      Implications: This paper describes how components of communication campaigns
      about cigarette constituents are perceived. Multiple elements of a tobacco
      constituent message, including type of constituent, image, and message source may
      influence the reception of messages among current smokers. Communication
      campaigns targeting smokers that utilize arsenic as the tobacco constituent,
      visual imagery, and the FDA logo may be particularly effective in changing key
      outcomes among smokers. The effects of such campaigns should be examined, as well
      as the mechanisms through which such campaigns affect change.

PMID- 29059360
TI  - Clinical Management of Insomnia Disorder.

PMID- 29059361
TI  - Surgical treatment of an extracranial carotid artery aneurysm in a child by an
      arterial autograft.
AB  - We report a symptomatic aneurysm of the left common carotid artery (LCCA) in a 6
      year-old boy. The patient had been diagnosed and treated 3 years earlier for an
      isolation of the LCCA with a right-sided aortic arch. At the age of 3 years, the
      LCCA was reimplanted in the ascending aorta. Three years later, the patient
      developed a voluminous aneurysm of the LCCA complicated by stroke. An arterial
      graft was used for the carotid reconstruction with good long-term patency and no
      aneurysm evolution.

PMID- 29059363
TI  - Consortium on Methods Evaluating Tobacco: Research Tools to Inform US Food and
      Drug Administration Regulation of Snus.
AB  - Introduction: The US Food and Drug Administration (FDA) has purview over tobacco
      products. To set policy, the FDA must rely on sound science, yet most existing
      tobacco research methods have not been designed to specifically inform
      regulation. The NCI and FDA-funded Consortium on Methods Evaluating Tobacco
      (COMET) was established to develop and assess valid and reliable methods for
      tobacco product evaluation. The goal of this article is to describe these
      assessment methods using a US manufactured "snus" as the test product. Methods:
      In designing studies that could inform FDA regulation, COMET has taken a
      multidisciplinary approach that includes experimental animal models and a range
      of human studies that examine tobacco product appeal, addictiveness, and
      toxicity. This article integrates COMET's findings over the last 4 years.
      Results: Consistency in results was observed across the various studies, lending
      validity to our methods. Studies showed low abuse liability for snus and low
      levels of consumer demand. Toxicity was less than cigarettes on some biomarkers
      but higher than medicinal nicotine. Conclusions: Using our study methods and the
      convergence of results, the snus that we tested as a potential modified risk
      tobacco product is likely to neither result in substantial public health harm nor
      benefit. Implications: This review describes methods that were used to assess the
      appeal, abuse liability, and toxicity of snus. These methods included animal,
      behavioral economics, consumer perception studies, and clinical trials. Across
      these varied methods, study results showed low abuse-liability and appeal of the
      snus product we tested. In several studies, demand for snus was lower than for
      less toxic nicotine gum. The consistency and convergence of results across a
      range of multi-disciplinary studies lends validity to our methods and suggests
      that promotion of snus as a modified risk tobacco products is unlikely to produce
      substantial public health benefit or harm.

PMID- 29059364
TI  - US Adult Interest in Less Harmful and Less Addictive Hypothetical Modified Risk
      Tobacco Products.
AB  - Introduction: Tobacco companies have a history of making health claims about
      their new products. Such claims are now regulated by the US Food and Drug
      Administration. We examined consumer interest in hypothetical modified risk
      tobacco products (MRTPs) among current, former, and never established smokers and
      examined whether interest was associated with beliefs about tobacco and cancer.
      Methods: Data were analyzed from the US nationally representative 2015 Health
      Information National Trends Survey (HINTS-FDA 2015; N = 3738). Interest in
      hypothetical MRTPs was assessed by asking participants their likelihood of using
      tobacco products claiming to be less addictive and less harmful than other
      products. Results: About half of current smokers and a tenth of both former and
      never smokers reported they were "somewhat" or "very" likely to try hypothetical
      MRTPs claiming to be less harmful or less addictive. Female smokers, former
      smokers with lower smoking harm perceptions, and never smokers who are young
      adults or without college education expressed more interest in these products.
      Interest in using these products was positively associated with believing that
      smoking status is a changeable individual characteristic and that it is possible
      for tobacco products to be made without some harmful chemicals. Conclusion: We
      identified several subgroups of current, former, and never smokers who may be
      particularly affected by the marketing of MRTPs and therefore important to study
      to inform models of the potential population health impact of authorizing the
      marketing of MRTPs. Implications: Findings about interest in hypothetical MRTPs
      can inform models of how the marketing of MRTPs could affect population health.
      Understanding which subgroups are particularly interested in MRTPs can help
      determine who might be important to study to inform these models. We identified
      several groups who may warrant specific attention: smokers who are female, former
      smokers who hold low harm perceptions of smoking, never smokers who are young
      adults or have a high school education or less, people who believe that smoking
      is a changeable individual characteristic, and people who believe that it is
      possible to make low chemical tobacco products.

PMID- 29059365
TI  - The SIN3A histone deacetylase complex is required for a complete transcriptional
      response to hypoxia.
AB  - Cells adapt to environmental changes, including fluctuations in oxygen levels,
      through the induction of specific gene expression programs. To identify genes
      regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells
      with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome
      wide binding profiles from the ENCODE project for factors that correlated with
      changes in transcription and identified binding of several components of the
      Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes
      repressed by hypoxia. SIN3A interference revealed that it participates in the
      downregulation of 75% of the hypoxia-repressed genes in endothelial cells.
      Unexpectedly, it also blunted the induction of 47% of the upregulated genes,
      suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq
      experiments showed that SIN3A preferentially localizes to the promoter region of
      actively transcribed genes and that SIN3A signal was enriched in hypoxia
      repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was
      not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our
      results reveal a prominent role for SIN3A in the transcriptional response to
      hypoxia and suggest a model where modulation of the associated histone
      deacetylase activity, rather than its recruitment, determines the transcriptional
      output.

PMID- 29059366
TI  - SBCDDB: Sleeping Beauty Cancer Driver Database for gene discovery in mouse models
      of human cancers.
AB  - Large-scale oncogenomic studies have identified few frequently mutated cancer
      drivers and hundreds of infrequently mutated drivers. Defining the biological
      context for rare driving events is fundamentally important to increasing our
      understanding of the druggable pathways in cancer. Sleeping Beauty (SB)
      insertional mutagenesis is a powerful gene discovery tool used to model human
      cancers in mice. Our lab and others have published a number of studies that
      identify cancer drivers from these models using various statistical and
      computational approaches. Here, we have integrated SB data from primary tumor
      models into an analysis and reporting framework, the Sleeping Beauty Cancer
      Driver DataBase (SBCDDB, http://sbcddb.moffitt.org), which identifies drivers in
      individual tumors or tumor populations. Unique to this effort, the SBCDDB
      utilizes a single, scalable, statistical analysis method that enables data to be
      grouped by different biological properties. This allows for SB drivers to be
      evaluated (and re-evaluated) under different contexts. The SBCDDB provides visual
      representations highlighting the spatial attributes of transposon mutagenesis and
      couples this functionality with analysis of gene sets, enabling users to
      interrogate relationships between drivers. The SBCDDB is a powerful resource for
      comparative oncogenomic analyses with human cancer genomics datasets for driver
      prioritization.

PMID- 29059367
TI  - Nicotine Metabolism-informed Care for Smoking Cessation: A Pilot Precision RCT.
AB  - Introduction: Varenicline doubles cessation over nicotine replacement therapy
      (NRT) patch for "normal," but not "slow," nicotine metabolizers, as assessed by
      the nicotine metabolite ratio (NMR). Metabolism-informed care (MIC) could improve
      outcomes by matching normal metabolizers with non-nicotine medication (e.g.,
      varenicline) and slow metabolizers with NRT patch. Methods: We conducted a
      feasibility randomized controlled trial of MIC versus guideline based care (GBC)
      among 81 outpatient adult daily smokers with medical comorbidity. Participants
      reported perceptions of MIC, underwent blood draw for NMR, and received expert
      cessation counseling. For MIC participants, medication selection was informed by
      NMR result (normal (>=0.31) vs. slow (< 0.31)). The primary outcome was MIC
      feasibility, reflected by attitudes toward MIC and by match rates between NMR and
      medication. Secondary endpoints (cessation confidence, medication use, smoking
      status) were assessed over 6 months to inform future studies. Results:
      Participants were median age 53 years, 46% female, 28% black, and ~90% endorsed
      MIC. Despite high varenicline prescription rates (~60%) in both arms, NMR
      medication matching was higher in MIC (84%) versus GBC (58%) participants
      (p=0.02); unadjusted odds ratio (OR) 3.67, 95% confidence interval [1.33, 11.00;
      p-value=0.02]. Secondary endpoints were similar at 1, 3, and 6 months.
      Conclusions: MIC, an NMR-based precision approach to smoking cessation, was
      acceptable to 90% of smokers and improved NMR-medication match rates more than 3
      fold compared to GBC, even with generally high use of varenicline. These data
      support the feasibility of MIC, which could maximize efficacy of smoking
      cessation medication while minimizing side effects and cost. Implications: Among
      treatment-seeking daily smokers with medical comorbidity, most viewed metabolism
      informed care (MIC), guided by the nicotine metabolism ratio (NMR), favorably,
      and were willing to accept MIC-guided medication. Compared to GBC participants
      (58%), more MIC participants (84%) were prescribed NMR-matched medication (i.e.,
      normal metabolizers received varenicline; slow metabolizers received NRT patch).
      MIC increased the odds of optimized matching between NMR and medication more than
      3-fold over GBC. Because the number needed to treat (NNT) to help one normal
      metabolizer quit smoking is only 4.9 for varenicline versus 26 for patch, broad
      implementation of MIC will improve drug efficacy in normal metabolizers as well
      as minimize side effects in slow metabolizers.

PMID- 29059368
TI  - Happiness as a Buffer of the Association Between Dependence and Acute Tobacco
      Abstinence Effects in African American Smokers.
AB  - Introduction: African American (AA) smokers are at disproportionate risk of
      tobacco dependence, utilizing smoking to regulate stress, and poor cessation
      outcomes. Positive emotional traits may function as coping factors that buffer
      the extent to which dependence increases vulnerability to adverse responses to
      acute tobacco abstinence (ie, tobacco withdrawal). This laboratory study examined
      subjective happiness (SH; dispositional orientation towards frequent and intense
      positive affect [PA] and life satisfaction) as a moderator of the relation
      between tobacco dependence and subjective and behavioral abstinence effects among
      AA smokers. Methods: AA smokers (N = 420, 39.0% female) completed self-report
      measures of tobacco dependence and SH followed by two counterbalanced
      experimental sessions (nonabstinent vs. 16-hour abstinent) involving self-report
      measures of composite withdrawal, urge to smoke, and mood, and a behavioral
      smoking task in which participants could: (1) earn money to delay smoking
      reinstatement, and (2) subsequently purchase cigarettes to smoke. Results:
      Tobacco dependence was positively associated with increased abstinence effects in
      composite withdrawal, urge to smoke, PA, and latency to smoking reinstatement (ps
      < .04). SH significantly moderated the relation between dependence and abstinence
      induced increases in composite withdrawal (beta = -.17, p < .001), such that the
      predictive power of dependence on withdrawal severity grew proportionately weaker
      as levels of SH increased. Conclusions: SH may insulate against adverse effects
      of dependence on withdrawal during acute smoking abstinence, particularly
      withdrawal symptom clusters that are craving- and mood-based. Consideration of
      positive emotional traits as stress-coping factors in the dependence-withdrawal
      link may be warranted in research and practice with AA smokers. Implications: The
      current study contributes to a growing body of literature examining the
      potentially advantageous role of positive emotional traits to smokers. We do so
      by identifying a relatively understudied psychological construct within tobacco
      research-subjective happiness-that may suppress the extent to which more severe
      tobacco dependence increases risk for subjective withdrawal-related distress
      during acute smoking abstinence in AA smokers. In doing so, the study provides a
      primer for future targeting of subjective happiness and other positive emotional
      traits as means to understand and treat acute tobacco abstinence effects among
      dependent AA smokers.

PMID- 29059369
TI  - Public Knowledge and Credibility Perceptions of the FDA as a Tobacco Regulator.
AB  - Introduction: Since the U.S. Food and Drug Administration (FDA) was granted
      regulatory authority over tobacco products in 2009, few studies have examined
      perceived credibility of the FDA in this role. The current study assessed
      knowledge and credibility of the FDA as a regulator of tobacco products. Methods:
      In a nationally representative survey of U.S. adults (N = 4758), we assessed
      knowledge that the FDA regulates the manufacture, distribution, and marketing of
      cigarettes, and credibility of the FDA as a tobacco regulator. We examined
      demographic differences in knowledge and credibility, and associations of
      knowledge and trust in government with credibility perceptions. Results: Less
      than half of respondents reported knowing the FDA regulates how cigarettes are
      sold (46.8%) and advertised (49.7%), and only 36.0% knew the FDA regulates how
      cigarettes are made, with few demographic differences. Respondents reported that
      the FDA was moderately credible in regulating tobacco. Knowledge of the FDA as a
      tobacco regulator and trust in government were the strongest predictors of
      credibility. Being of younger age, being White (compared to African American),
      and being male were associated with higher credibility ratings of the FDA.
      Conclusions: Much of the public still does not know that the FDA regulates
      tobacco products, and credibility perceptions are moderate. Greater knowledge of
      the FDA's regulatory role was associated with higher credibility; efforts that
      increase the public's understanding of the FDA's role as a tobacco regulator may
      positively impact views of the agency's credibility. This may in turn improve
      public reception to the FDA's messages and regulations. Implications: This study
      is the first to show nationally representative estimates of both knowledge and
      credibility of the FDA as a tobacco regulator. Our research shows further that
      knowledge of the FDA's tobacco regulatory roles is likely to be an important
      factor related to perceived credibility of the FDA. Increasing the public's
      knowledge of the FDA's roles may enhance the agency's credibility, which can
      improve public reception to messages and regulations.

PMID- 29059370
TI  - Faster family-wise error control for neuroimaging with a parametric bootstrap.
AB  - In neuroimaging, hundreds to hundreds of thousands of tests are performed across
      a set of brain regions or all locations in an image. Recent studies have shown
      that the most common family-wise error (FWE) controlling procedures in imaging,
      which rely on classical mathematical inequalities or Gaussian random field
      theory, yield FWE rates (FWER) that are far from the nominal level. Depending on
      the approach used, the FWER can be exceedingly small or grossly inflated. Given
      the widespread use of neuroimaging as a tool for understanding neurological and
      psychiatric disorders, it is imperative that reliable multiple testing procedures
      are available. To our knowledge, only permutation joint testing procedures have
      been shown to reliably control the FWER at the nominal level. However, these
      procedures are computationally intensive due to the increasingly available large
      sample sizes and dimensionality of the images, and analyses can take days to
      complete. Here, we develop a parametric bootstrap joint testing procedure. The
      parametric bootstrap procedure works directly with the test statistics, which
      leads to much faster estimation of adjusted p-values than resampling-based
      procedures while reliably controlling the FWER in sample sizes available in many
      neuroimaging studies. We demonstrate that the procedure controls the FWER in
      finite samples using simulations, and present region- and voxel-wise analyses to
      test for sex differences in developmental trajectories of cerebral blood flow.

PMID- 29059372
TI  - Disparities in the Receipt of Tobacco Treatment Counseling within the US Context
      of the Affordable Care Act and Meaningful Use Implementation.
AB  - Introduction: Disparities in receiving advice to quit smoking and other tobacco
      use from health professionals may contribute to the continuing gap in smoking
      prevalence among priority populations. Under the Affordable Care Act (ACA),
      beginning in 2010, tobacco cessation services are currently covered in private
      and public health insurance plans. Providers and hospitals are also incentivized
      through the Meaningful Use of Electronic Health Records (EHRs) to screen and
      document patients' tobacco use and deliver brief cessation counseling. This study
      analyzes trends and correlates of receiving health professionals' advice to quit
      and potential disparities among US adult smokers from 2010 to 2015. Methods: Data
      were from the National Health Interview Survey in 2010 and 2015. We analyzed the
      weighted prevalence of smokers' receipt of advice to quit smoking and other
      tobacco use from a health professional in 2010 and 2015 and correlates of
      receiving advice to quit. Results: Prevalence of receiving advice to quit from a
      health professional increased from 51.4% in 2010 to 60.6% in 2015. This positive
      trend was observed across tobacco disparity population groups. Survey year
      (2015), age (older), ethnicity (non-Hispanic), region (Northeast), poverty level
      (above 100% poverty level), past quit attempt, daily smoking, cigarettes per day
      (11+ per day), and psychological distress were associated with higher odds of
      receiving advice to quit. Conclusion: Based on national level data, receipt of
      advice to quit from health professionals increased between 2010 and 2015.
      However, disparities in receiving advice to quit from health professionals
      persist in certain populations. Implications: This study provides important data
      on the national trends in receipt of health professional advice to quit smoking
      and other tobacco use in the context of the ACA and Meaningful Use implementation
      and whether these policies helped to narrow the gaps in receipt of health
      professional advice among vulnerable populations.

PMID- 29059371
TI  - Randomized comparison of the clinical outcome of single versus multiple arterial
      grafts: the ROMA trial-rationale and study protocol.
AB  - SUMMARY: The primary hypothesis of the ROMA trial is that in patients undergoing
      primary isolated non-emergent coronary artery bypass grafting, the use of 2 or
      more arterial grafts compared with a single arterial graft (SAG) is associated
      with a reduction in the composite outcome of death from any cause, any stroke,
      post-discharge myocardial infarction and/or repeat revascularization. : The
      secondary hypothesis is that in these patients, the use of 2 or more arterial
      grafts compared with a SAG is associated with improved survival. The ROMA trial
      is a prospective, unblinded, randomized event-driven multicentre trial comprising
      at least 4300 subjects. Patients younger than 70 years with left main and/or
      multivessel disease will be randomized to a SAG or multiple arterial grafts to
      the left coronary system in a 1:1 fashion. Permuted block randomization
      stratified by the centre and the type of second arterial graft will be used. The
      primary outcome will be a composite of death from any cause, any stroke, post
      discharge myocardial infarction and/or repeat revascularization. The secondary
      outcome will be all-cause mortality. The primary safety outcome will be a
      composite of death from any cause, any stroke and any myocardial infarction. In
      all patients, 1 internal thoracic artery will be anastomosed to the left anterior
      descending coronary artery. For patients randomized to the SAG group, saphenous
      vein grafts will be used for all non-left anterior descending target vessels. For
      patients randomized to the multiple arterial graft group, the main target vessel
      of the lateral wall will be grafted with either a radial artery or a second
      internal thoracic artery. Additional grafts for the multiple arterial graft group
      can be saphenous veins or supplemental arterial conduits. To detect a 20%
      relative reduction in the primary outcome, with 90% power at 5% alpha and
      assuming a time-to-event analysis, the sample size must include 845 events (and
      3650 patients). To detect a 20% relative reduction in the secondary outcome, with
      80% power at 5% alpha, the sample size must include 631 events (and 3650
      patients). To be conservative, the sample size will be set at 4300 patients. The
      primary outcome will be tested according to the intention-to-treat principle. The
      primary analysis will be a Cox proportional hazards regression model, with the
      treatment arm included as a covariate. If non-proportional hazards are observed,
      alternatives to Cox proportional hazards regression will be explored.

PMID- 29059374
TI  - The Pancreatic Expression Database: 2018 update.
AB  - The Pancreatic Expression Database (PED, http://www.pancreasexpression.org)
      continues to be a major resource for mining pancreatic -omics data a decade after
      its initial release. Here, we present recent updates to PED and describe its
      evolution into a comprehensive resource for extracting, analysing and integrating
      publicly available multi-omics datasets. A new analytical module has been
      implemented to run in parallel with the existing literature mining functions.
      This analytical module has been created using rich data content derived from
      pancreas-related specimens available through the major data repositories (GEO,
      ArrayExpress) and international initiatives (TCGA, GENIE, CCLE). Researchers have
      access to a host of functions to tailor analyses to meet their needs. Results are
      presented using interactive graphics that allow the molecular data to be
      visualized in a user-friendly manner. Furthermore, researchers are provided with
      the means to superimpose layers of molecular information to gain greater insight
      into alterations and the relationships between them. The literature-mining module
      has been improved with a redesigned web appearance, restructured query platforms
      and updated annotations. These updates to PED are in preparation for its
      integration with the Pancreatic Cancer Research Fund Tissue Bank (PCRFTB), a
      vital resource of pancreas cancer tissue for researchers to support and promote
      cutting-edge research.

PMID- 29059373
TI  - Genome-wide interaction study of smoking behavior and non-small cell lung cancer
      risk in Caucasian population.
AB  - Non-small cell lung cancer is the most common type of lung cancer. Both
      environmental and genetic risk factors contribute to lung carcinogenesis. We
      conducted a genome-wide interaction analysis between single nucleotide
      polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a
      European-descent population. We adopted a two-step analysis strategy in the
      discovery stage: we first conducted a case-only interaction analysis to assess
      the relationship between SNPs and smoking behavior using 13336 non-small cell
      lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using
      a standard case-control interaction analysis including 13970 controls. The
      significant SNPs with P-value <3.5 * 10-5 (correcting for multiple tests) from
      the case-control analysis in the discovery stage were further validated using an
      independent replication dataset comprising 5377 controls and 3054 non-small cell
      lung cancer cases. We further stratified the analysis by histological subtypes.
      Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer
      risk. The interaction odds ratio and meta-analysis P-value for these two SNPs
      were 1.24 with 6.96 * 10-7 and 1.37 with 3.49 * 10-7, respectively. In addition,
      interaction of smoking with rs4751674 was identified in squamous cell lung
      carcinoma with an odds ratio of 0.58 and P-value of 8.12 * 10-7. This study is by
      far the largest genome-wide SNP-smoking interaction analysis reported for lung
      cancer. The three identified novel SNPs provide potential candidate biomarkers
      for lung cancer risk screening and intervention. The results from our study
      reinforce that gene-smoking interactions play important roles in the etiology of
      lung cancer and account for part of the missing heritability of this disease.

PMID- 29059376
TI  - Association of body size metrics with left atrial phasic volumes and reservoir
      function in the elderly.
AB  - Aims: General obesity, defined by increased body mass index (BMI), is associated
      with left atrial (LA) enlargement, a marker of cardiovascular risk in the general
      population. The association between abdominal adiposity, defined by increased
      waist circumference (WC) or waist-to-hip ratio (WHR), and LA phasic volumes and
      reservoir function is not well known. The aim of this study was to evaluate the
      association between different body size metrics and LA phasic volumes and
      reservoir function in the elderly. Methods and results: Participants from the
      CABL (Cardiovascular Abnormalities and Brain Lesions) study underwent measurement
      of BMI, WC, and WHR. The LA maximum (LAVmax) and minimum (LAVmin) volumes, and LA
      reservoir function, measured as total emptying volume index (LAEVI), total
      emptying fraction (LAEF), and expansion index (LAEI), were assessed by real-time
      3D echocardiography. The study population included 629 participants (mean age 71
      +/- 9 years, 61% women). Mean BMI was 27.9 +/- 4.6 kg/m2, WC was 95.0 +/- 11.7
      cm, WHR was 0.91 +/- 0.08. After adjusting for multiple potential confounders
      (demographics, cardiovascular risk factors, left ventricular mass index, and
      diastolic function), higher WC was significantly associated with higher LA phasic
      volumes (LAVmax, beta = 0.10, P = 0.007 and LAVmin, beta = 0.12, P = 0.002) and
      reduced reservoir function (LAEVI, beta = -0.15, P = 0.001 and LAEI, beta = 
      0.09, P = 0.027). WHR was significantly associated only with reduced reservoir
      function (LAEVI, beta = -0.11, P = 0.012), whereas BMI was not associated with
      either LA phasic volumes or reservoir function. Conclusion: In the elderly, WC
      may have more impact on LA phasic volumes and reservoir function, and therefore
      risk for cardiovascular events, than WHR and BMI.

PMID- 29059375
TI  - Translational co-regulation of a ligand and inhibitor by a conserved RNA element.
AB  - In many organisms, transcriptional and post-transcriptional regulation of
      components of pathways or processes has been reported. However, to date, there
      are few reports of translational co-regulation of multiple components of a
      developmental signaling pathway. Here, we show that an RNA element which we
      previously identified as a dorsal localization element (DLE) in the 3'UTR of
      zebrafish nodal-related1/squint (ndr1/sqt) ligand mRNA, is shared by the related
      ligand nodal-related2/cyclops (ndr2/cyc) and the nodal inhibitors, lefty1 (lft1)
      and lefty2 mRNAs. We investigated the activity of the DLEs through functional
      assays in live zebrafish embryos. The lft1 DLE localizes fluorescently labeled
      RNA similarly to the ndr1/sqt DLE. Similar to the ndr1/sqt 3'UTR, the lft1 and
      lft2 3'UTRs are bound by the RNA-binding protein (RBP) and translational
      repressor, Y-box binding protein 1 (Ybx1), whereas deletions in the DLE abolish
      binding to Ybx1. Analysis of zebrafish ybx1 mutants shows that Ybx1 represses
      lefty1 translation in embryos. CRISPR/Cas9-mediated inactivation of human YBX1
      also results in human NODAL translational de-repression, suggesting broader
      conservation of the DLE RNA element/Ybx1 RBP module in regulation of Nodal
      signaling. Our findings demonstrate translational co-regulation of components of
      a signaling pathway by an RNA element conserved in both sequence and structure
      and an RBP, revealing a 'translational regulon'.

PMID- 29059377
TI  - Changes in Puffing Topography and Nicotine Consumption Depending on the Power
      Setting of Electronic Cigarettes.
AB  - Introduction: The study purpose was to evaluate changes in puffing topography of
      experienced electronic cigarette users (vapers) when changing power settings in
      electronic cigarette battery devices. Methods: Experienced adult vapers (n = 21)
      were recruited. Participants used their own liquids and an atomizer and battery
      provided by the researchers. Two 30-minute sessions were performed, with the
      device power set at 6 W and 10 W, in a randomized, crossover, participant-blinded
      design. Puff number and duration (mean [SD]) were recorded in the provided
      electronic cigarette battery device, whereas the atomizers were weighted before
      and after use to determine liquid and nicotine consumption. Results: Puff number
      and puff duration were lower at 10 W (46 [16] puffs and 3.8 [0.8] s) compared
      with 6 W (57 [20] puffs and 4.6 [1.0] s). Liquid and nicotine consumption was
      higher at 10 W (373 [176] mg and 4.2 [2.4] mg, respectively) compared with 6 W
      (308 [165] mg and 3.5 [2.3] mg, respectively). Vapers reported more aerosol
      volume and ease of use at 10 W compared with 6 W. Conclusions: The study
      identified an attempt for compensatory puffing patterns and nicotine self
      titration, with a change in puffing patterns (puff number and duration) observed
      when changing the power settings of an e-cigarette device. Implications:
      Compensatory smoking behavior and nicotine self-titration is a well-established
      phenomenon. In electronic cigarettes, changing nicotine concentration in the
      liquid has been shown to trigger a compensatory puffing pattern. Herein, power
      setting of the electronic cigarette device was found to be a parameter associated
      with changes in puffing behavior, whereas higher power was preferable for the
      participants. These findings could contribute to the understanding of patterns of
      electronic cigarette use and could explain the preference of dedicated vapers to
      higher power devices. Additionally, laboratory studies evaluating aerosol
      emissions should consider using different puffing patterns according to the power
      settings tested.

PMID- 29059378
TI  - Characterization of the APLF FHA-XRCC1 phosphopeptide interaction and its
      structural and functional implications.
AB  - Aprataxin and PNKP-like factor (APLF) is a DNA repair factor containing a
      forkhead-associated (FHA) domain that supports binding to the phosphorylated FHA
      domain binding motifs (FBMs) in XRCC1 and XRCC4. We have characterized the
      interaction of the APLF FHA domain with phosphorylated XRCC1 peptides using
      crystallographic, NMR, and fluorescence polarization studies. The FHA-FBM
      interactions exhibit significant pH dependence in the physiological range as a
      consequence of the atypically high pK values of the phosphoserine and
      phosphothreonine residues and the preference for a dianionic charge state of FHA
      bound pThr. These high pK values are characteristic of the polyanionic peptides
      typically produced by CK2 phosphorylation. Binding affinity is greatly enhanced
      by residues flanking the crystallographically-defined recognition motif,
      apparently as a consequence of non-specific electrostatic interactions,
      supporting the role of XRCC1 in nuclear cotransport of APLF. The FHA domain
      dependent interaction of XRCC1 with APLF joins repair scaffolds that support
      single-strand break repair and non-homologous end joining (NHEJ). It is suggested
      that for double-strand DNA breaks that have initially formed a complex with PARP1
      and its binding partner XRCC1, this interaction acts as a backup attempt to
      intercept the more error-prone alternative NHEJ repair pathway by recruiting Ku
      and associated NHEJ factors.

PMID- 29059379
TI  - CirGRDB: a database for the genome-wide deciphering circadian genes and
      regulators.
AB  - Circadian rhythms govern various kinds of physiological and behavioral functions
      of the living organisms, and disruptions of the rhythms are highly detrimental to
      health. Although several databases have been built for circadian genes, a
      resource for comprehensive post-transcriptional regulatory information of
      circadian RNAs and expression patterns of disease-related circadian RNAs is still
      lacking. Here, we developed CirGRDB (http://cirgrdb.biols.ac.cn) by integrating
      more than 4936 genome-wide assays, with the aim of fulfilling the growing need to
      understand the rhythms of life. CirGRDB presents a friendly web interface that
      allows users to search and browse temporal expression patterns of interested
      genes in 37 human/mouse tissues or cell lines, and three clinical disorders
      including sleep disorder, aging and tumor. More importantly, eight kinds of
      potential transcriptional and post-transcriptional regulators involved in the
      rhythmic expression of the specific genes, including transcription factors,
      histone modifications, chromatin accessibility, enhancer RNAs, miRNAs, RNA
      binding proteins, RNA editing and RNA methylation, can also be retrieved.
      Furthermore, a regulatory network could be generated based on the regulatory
      information. In summary, CirGRDB offers a useful repository for exploring disease
      related circadian RNAs, and deciphering the transcriptional and post
      transcriptional regulation of circadian rhythms.

PMID- 29059380
TI  - Expression of Arabidopsis class 1 phytoglobin (AtPgb1) delays death and
      degradation of the root apical meristem during severe PEG-induced water deficit.
AB  - Maintenance of a functional root is fundamental to plant survival in response to
      some abiotic stresses, such as water deficit. In this study, we found that
      overexpression of Arabidopsis class 1 phytoglobin (AtPgb1) alleviated the growth
      retardation of polyethylene glycol (PEG)-induced water stress by reducing
      programmed cell death (PCD) associated with protein folding in the endoplasmic
      reticulum (ER). This was in contrast to PEG-stressed roots down-regulating AtPgb1
      that exhibited extensive PCD and reduced expression of several attenuators of ER
      stress, including BAX Inhibitor-1 (BI-1). The death program experienced by the
      suppression of AtPgb1 in stressed roots was mediated by reactive oxygen species
      (ROS) and ethylene. Suppression of ROS synthesis or ethylene perception reduced
      PCD and partially restored root growth. The PEG-induced cessation of root growth
      was preceded by structural changes in the root apical meristem (RAM), including
      the loss of cell and tissue specification, possibly as a result of alterations in
      PIN1- and PIN4-mediated auxin accumulation at the root pole. These events were
      attenuated by the overexpression of AtPgb1 and aggravated when AtPgb1 was
      suppressed. Specifically, suppression of AtPgb1 compromised the functionality of
      the WOX5-expressing quiescent cells (QCs), leading to the early and premature
      differentiation of the adjacent columella stem cells and to a rapid reduction in
      meristem size. The expression and localization of other root domain markers, such
      as SCARECROW (SCR), which demarks the endodermis and QCs, and WEREWOLF (WER),
      which specifies the lateral root cap, were also most affected in PEG-treated
      roots with suppressed AtPgb1. Collectively, the results demonstrate that AtPgb1
      exercises a protective role in roots exposed to lethal levels of PEG, and suggest
      a novel function of this gene in ensuring meristem functionality through the
      retention of cell fate specification.

PMID- 29059381
TI  - Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype,
      Inheritance, Sex, Age, Hormonal Status, and BMI.
AB  - Context: Albright hereditary osteodystrophy (AHO) is caused by heterozygous
      inactivating mutations in GNAS. Depending on the parental origin of the mutated
      allele, patients develop either pseudohypoparathyroidism type 1A (PHP1A), with
      multihormone resistance and severe obesity, or pseudopseudohypoparathyroidism
      (PPHP), without hormonal abnormalities or marked obesity. Subcutaneous
      ossifications (SCOs) are a source of substantial morbidity in both PHP1A and
      PPHP. Objective: This study investigated the previously undetermined prevalence
      of SCO formation in PHP1A vs PPHP as well as possible correlations with genotype,
      sex, age, hormonal resistance, and body mass index (BMI). Design: This study
      evaluated patients with AHO for SCOs by physical examination performed by one
      consistent physician over 16 years. Setting: Albright Clinic, Kennedy Krieger
      Institute; Institute for Clinical and Translational Research, Johns Hopkins
      Hospital; Albright Center, Connecticut Children's Medical Center. Patients: We
      evaluated 67 patients with AHO (49 with PHP1A, 18 with PPHP) with documented
      mutations in GNAS. Main Outcome Measures: Relationships of SCOs to genotype, sex,
      age, hormonal resistance, and BMI. Results: Forty-seven of 67 participants
      (70.1%) had SCOs. Patients with PHP1A and PPHP had similar prevalences and
      degrees of ossification formation. Patients with frameshift and nonsense
      mutations had much more extensive SCOs than those with missense mutations. Males
      were affected more than females. There was no correlation with hormonal status or
      BMI. Conclusions: There is a similar prevalence of SCOs in PHP1A and PPHP, and
      the extent of SCO formation correlates with the severity of the mutation. Males
      are affected more extensively than females, and the SCOs tend to worsen with age.

PMID- 29059382
TI  - dreamBase: DNA modification, RNA regulation and protein binding of expressed
      pseudogenes in human health and disease.
AB  - Although thousands of pseudogenes have been annotated in the human genome, their
      transcriptional regulation, expression profiles and functional mechanisms are
      largely unknown. In this study, we developed dreamBase
      (http://rna.sysu.edu.cn/dreamBase) to facilitate the investigation of DNA
      modification, RNA regulation and protein binding of potential expressed
      pseudogenes from multidimensional high-throughput sequencing data. Based on ~5500
      ChIP-seq and DNase-seq datasets, we identified genome-wide binding profiles of
      various transcription-associated factors around pseudogene loci. By integrating
      ~18 000 RNA-seq data, we analysed the expression profiles of pseudogenes and
      explored their co-expression patterns with their parent genes in 32 cancers and
      31 normal tissues. By combining microRNA binding sites, we demonstrated complex
      post-transcriptional regulation networks involving 275 microRNAs and 1201
      pseudogenes. We generated ceRNA networks to illustrate the crosstalk between
      pseudogenes and their parent genes through competitive binding of microRNAs. In
      addition, we studied transcriptome-wide interactions between RNA binding proteins
      (RBPs) and pseudogenes based on 458 CLIP-seq datasets. In conjunction with
      epitranscriptome sequencing data, we also mapped 1039 RNA modification sites onto
      635 pseudogenes. This database will provide insights into the transcriptional
      regulation, expression, functions and mechanisms of pseudogenes as well as their
      roles in biological processes and diseases.

PMID- 29059383
TI  - FlavorDB: a database of flavor molecules.
AB  - Flavor is an expression of olfactory and gustatory sensations experienced through
      a multitude of chemical processes triggered by molecules. Beyond their key role
      in defining taste and smell, flavor molecules also regulate metabolic processes
      with consequences to health. Such molecules present in natural sources have been
      an integral part of human history with limited success in attempts to create
      synthetic alternatives. Given their utility in various spheres of life such as
      food and fragrances, it is valuable to have a repository of flavor molecules,
      their natural sources, physicochemical properties, and sensory responses.
      FlavorDB (http://cosylab.iiitd.edu.in/flavordb) comprises of 25,595 flavor
      molecules representing an array of tastes and odors. Among these 2254 molecules
      are associated with 936 natural ingredients belonging to 34 categories. The
      dynamic, user-friendly interface of the resource facilitates exploration of
      flavor molecules for divergent applications: finding molecules matching a desired
      flavor or structure; exploring molecules of an ingredient; discovering novel food
      pairings; finding the molecular essence of food ingredients; associating chemical
      features with a flavor and more. Data-driven studies based on FlavorDB can pave
      the way for an improved understanding of flavor mechanisms.

PMID- 29059384
TI  - Strategies for radiation dose reduction in nuclear cardiology and cardiac
      computed tomography imaging: a report from the European Association of
      Cardiovascular Imaging (EACVI), the Cardiovascular Committee of European
      Association of Nuclear Medicine (EANM), and the European Society of
      Cardiovascular Radiology (ESCR).

PMID- 29059385
TI  - Snail1 transcription factor controls telomere transcription and integrity.
AB  - Besides controlling epithelial-to-mesenchymal transition (EMT) and cell invasion,
      the Snail1 transcriptional factor also provides cells with cancer stem cell
      features. Since telomere maintenance is essential for stemness, we have examined
      the control of telomere integrity by Snail1. Fluorescence in situ hybridization
      (FISH) analysis indicates that Snail1-depleted mouse mesenchymal stem cells (MSC)
      have both a dramatic increase of telomere alterations and shorter telomeres.
      Remarkably, Snail1-deficient MSC present higher levels of both telomerase
      activity and the long non-coding RNA called telomeric repeat-containing RNA
      (TERRA), an RNA that controls telomere integrity. Accordingly, Snail1 expression
      downregulates expression of the telomerase gene (TERT) as well as of TERRA 2q,
      11q and 18q. TERRA and TERT are transiently downregulated during TGFbeta-induced
      EMT in NMuMG cells, correlating with Snail1 expression. Global transcriptome
      analysis indicates that ectopic expression of TERRA affects the transcription of
      some genes induced during EMT, such as fibronectin, whereas that of TERT does not
      modify those genes. We propose that Snail1 repression of TERRA is required not
      only for telomere maintenance but also for the expression of a subset of
      mesenchymal genes.

PMID- 29059386
TI  - Monitoring Tobacco Brand Websites to Understand Marketing Strategies Aimed at
      Tobacco Product Users and Potential Users.
AB  - Introduction: Limited information exists about strategies and methods used on
      brand marketing websites to transmit pro-tobacco messages to tobacco users and
      potential users. This study compared age verification methods, themes,
      interactive activities and links to social media across tobacco brand websites.
      Methods: This study examined 12 tobacco brand websites representing four tobacco
      product categories: cigarettes, cigar/cigarillos, smokeless tobacco, and e
      cigarettes. Website content was analyzed by tobacco product category and data
      from all website visits (n = 699) were analyzed. Adult smokers (n = 32) coded
      websites during a one-year period, indicating whether or not they observed any of
      53 marketing themes, seven interactive activities, or five external links to
      social media sites. Results: Most (58%) websites required online registration
      before entering, however e-cigarette websites used click-through age
      verification. Compared to cigarette sites, cigar/cigarillo sites were more likely
      to feature themes related to "party" lifestyle, and e-cigarette websites were
      much more likely to feature themes related to harm reduction. Cigarette sites
      featured greater levels of interactive content compared to other tobacco
      products. Compared to cigarette sites, cigar/cigarillo sites were more likely to
      feature activities related to events and music. Compared to cigarette sites, both
      cigar and e-cigarette sites were more likely to direct visitors to external
      social media sites. Conclusion: Marketing methods and strategies normalize
      tobacco use by providing website visitors with positive themes combined with
      interactive content, and is an area of future research. Moreover, all tobacco
      products under federal regulatory authority should be required to use more
      stringent age verification gates. Implications: Findings indicate that the Food
      and Drug Administration (FDA) should require brand websites of all tobacco
      products under its regulatory authority use more stringent age verification gates
      by requiring all visitors be at least 18 years of age and register online prior
      to entry. This is important given that marketing strategies may encourage
      experimentation with tobacco or deter quit attempts among website visitors.
      Future research should examine the use of interactive activities and social media
      on a wide variety of tobacco brand websites as interactive content is associated
      with more active information processing.

PMID- 29059387
TI  - Parental Perceptions and Misconceptions of Child Tobacco Smoke Exposure.
AB  - Introduction: Forty percent of young children worldwide are exposed to the
      harmful effects of tobacco smoke, predominantly by parental smoking. Little is
      known about why parents regularly expose their children to these risks; perhaps
      parents underestimate the degree of exposure. Qualitative methods were used to
      investigate parental perceptions of tobacco smoke exposure. Methods: Sixty-five
      in-depth interviews were conducted with parents of young children in smoking
      families in central Israel. Parents were asked to explain what "exposure to
      smoking" meant. Thematic analysis was performed, a conceptual model of
      perceptions was built, and misconceptions were identified. Results: Parents
      reported that exposure occurs when smoke or smokers are visible, when smoke can
      be smelled, felt, or inhaled, or when it "reaches" an individual. Conversely,
      some believed that exposure does not occur in the absence of odor, visible smoke,
      or smokers or if smoking occurs outdoors or in indoor ventilated environments.
      Proximity in space and time affected perceptions of exposure; some parents
      believed that smoke does not spread far but dissipates rapidly. There was some
      uncertainty regarding whether or not exposure was occurring. Conclusions:
      Awareness of child exposure to tobacco smoke among parents in this study was
      based on sensory perceptions in the context of the physical environment. The
      limited capacity of humans to perceive tobacco smoke can lead to misconceptions
      about exposure. In order to protect children, parents must be convinced that
      exposure can occur even in situations where they are unable to sense it.
      Implications: Parents use sensory perceptions (sight, smell, and feel) in the
      context of the physical environment to assess whether or not their children are
      exposed to tobacco smoke. Because 85% of smoke is invisible and the sense of
      smell is unreliable, assessments based on sensory perceptions cannot provide
      accurate information about the presence of tobacco smoke. In order to protect
      children, parents must be convinced that exposure can occur even in situations
      where they are unable to sense it. The scientific information summarized here
      about exposure in common situations should be useful in persuading parents to
      protect their children. Clinical Trial Registration: This study is registered as
      a Phase I study which is part of a larger research endeavor entitled: A program
      to protect young children from tobacco smoke exposure. Registration number:
      NCT01335178.

PMID- 29059388
TI  - Optimization of folic acid supplementation in the prevention of neural tube
      defects.
AB  - Background: We examined the relationship between timing and duration of folic
      acid (FA) supplementation in achieving red blood cell (RBC) folate levels in
      early pregnancy which are optimal (>906 nmol/l) for the prevention of neural tube
      defects (NTDs). Methods: Clinical, FA supplementation and dietary folate details
      were computerized at the first antenatal visit. Maternal blood samples were
      analysed for RBC and serum folate. Results: Of the 502 women, 98.2% (n = 493)
      reported taking FA. There was a positive correlation between duration of
      supplementation and both RBC folate (r = 0.43, P < 0.001) and serum folate (rho =
      0.29, P < 0.001). The optimal RBC folate level was achieved in 80.4% (n = 46) of
      women who started FA 400 MUg 4-8 weeks before their LMP compared with only 53.6%
      (n = 153) in women who started 4-8 weeks after their LMP (P < 0.001).
      Conclusions: This study provides, for the first time, information on both the
      timing and duration of FA that will achieve the optimum RBC folate levels
      associated with the prevention of NTDs. Women who are taking FA (400 MUg) need to
      start before they conceive.

PMID- 29059389
TI  - Pilot Study of a Tailored Smoking Cessation Intervention for Individuals in
      Treatment for Opioid Dependence.
AB  - Introduction: Over 85% of opioid-dependent individuals in methadone treatment
      smoke cigarettes; however, smoking cessation interventions are minimally
      effective in this population. To better help opioid-dependent individuals quit
      smoking, we developed and pilot-tested an intervention, based in the Information
      Motivation-Behavioral Skills (IMB) model of behavior change, which could be
      tailored to address individual barriers to smoking cessation in this population.
      Methods: We randomized participants (n = 83) in methadone treatment to the eight
      session, IMB model-based, intervention plus nicotine replacement therapy
      (intervention, n = 41) or a facilitated referral to the state Quitline (control,
      n = 42). All participants completed assessments at baseline, 3 months, and 6
      months. Results: Intervention participants completed a median of five sessions
      (interquartile range [IQR] 3-8) and had significantly higher intervention
      satisfaction than control participants. Intervention participants reported
      smoking significantly fewer cigarettes per day at 3 months (median [IQR] = 6 [4
      15]) and 6 months (median [IQR] = 8 [4-14]) as compared control participants at 3
      months (median [IQR] = 10 [5-20]) and 6 months (median [IQR] = 10 [6-20]). Fifty
      six percent of the intervention group and 41% of the control group a made a quit
      attempt during the study (p = .16). At 3 months, 7% (n = 3) of intervention
      participants and none of the control participants were abstinent from smoking (p
      = .23). At 6 months, 2% of participants in both groups were abstinent. Twenty
      four percent and 10% of the intervention and control group participants,
      respectively, reported 20 or more smoke-free days (p = .43). Conclusions: An IMB
      model-based smoking cessation intervention for opioid-dependent smokers is
      feasible and acceptable in methadone treatment and may help methadone maintained
      smokers cut down on their smoking. Implications: This is the first study of a
      tailored, IMB Model-based, smoking cessation intervention for opioid dependent
      smokers. Results showed that opioid dependent smokers are willing and able to
      participate in an IMB model-based smoking cessation intervention, and this
      intervention may help this population cut down on their smoking. Also, the
      Quitline seems less feasible and acceptable for this population than a face-to
      face intervention. Further research is needed to determine how to integrate
      smoking cessation treatment into methadone programs and how to improve
      interventions so that treatment gains can lead to long-term abstinence in this
      population.

PMID- 29059390
TI  - Cracking the Betel Nut: Cholinergic Activity of Areca Alkaloids and Related
      Compounds.
AB  - Introduction: The use of betel quid is the most understudied major addiction in
      the world. The neuropsychological activity of betel quid has been attributed to
      alkaloids of Areca catechu. With the goal of developing novel addiction
      treatments, we evaluate the muscarinic and nicotinic activity of the four major
      Areca alkaloids: arecoline, arecaidine, guvacoline, and guvacine and four
      structurally related compounds. Methods: Acetylcholine receptors were expressed
      in Xenopus oocytes and studied with two-electrode voltage clamp. Results: Both
      arecoline- and guvacoline-activated muscarinic acetylcholine receptors (mAChR),
      while only arecoline produced significant activation of nicotinic AChR (nAChR).
      We characterized four additional arecoline-related compounds, seeking an analog
      that would retain selective activity for a alpha4* nAChR, with diminished effects
      on mAChR and not be a desensitizer of alpha7 nAChR. We show that this profile is
      largely met by isoarecolone. Three additional arecoline analogs were
      characterized. While the quaternary dimethyl analog had a broad range of
      activities, including activation of mAChR and muscle-type nAChR, the methyl
      analog only activated a range of alpha4* nAChR, albeit with low potency. The
      ethyl analog had no detectable cholinergic activity. Conclusions: Evidence
      indicates that alpha4* nAChR are at the root of nicotine addiction, and this may
      also be the case for betel addiction. Our characterization of isoarecolone and 1
      (4-methylpiperazin-1-yl) ethanone as truly selective alpha4*nAChR selective
      partial agonists with low muscarinic activity may point toward a promising new
      direction for the development of drugs to treat both nicotine and betel
      addiction. Implications: Nearly 600 million people use Areca nut, often with
      tobacco. Two of the Areca alkaloids are muscarinic acetylcholine receptor
      agonists, and one, arecoline, is a partial agonist for the alpha4* nicotinic
      acetylcholine receptors (nAChR) associated with tobacco addiction. The profile of
      arecoline activity suggested its potential to be used as a scaffold for
      developing new tobacco cessation drugs if analogs can be identified that retain
      the same nicotinic receptor selectivity without muscarinic activity. We report
      that isoarecolone is a selective partial agonist for alpha4* nAChR with minimal
      muscarinic activity and 1-(4-methylpiperazin-1-yl) ethanone has similar nAChR
      selectivity and no detectable muscarinic action.

PMID- 29059391
TI  - The Power of Product Innovation: Smokers' Perceptions of Capsule Cigarettes.
AB  - Introduction: Since being brought to market in 2007, cigarettes with capsules in
      the filter that can be burst to change the flavor have had remarkable global
      success, highlighting the importance of product innovation for tobacco companies.
      Very few studies have explored how these products are perceived by smokers
      however. This paper sought to address this gap by exploring smokers' awareness of
      cigarettes with one or two flavor-changing capsules in the filter and the appeal
      of these products. Methods: Twenty focus groups were conducted in Glasgow and
      Edinburgh in 2015 with current smokers (N = 120), segmented by age (16-17, 18-24,
      25-35, 36-50, >50), gender, and social grade. Results: Awareness, use and appeal
      of capsule cigarettes was greater among younger adults (16-35 years), who showed
      most interest in these products. Those who perceived capsules positively
      mentioned multiple benefits: the ability to burst the capsule, convenience of
      being able to share cigarettes among menthol and nonmenthol smokers, better
      taste, fresher breath, reduced smell, and greater discretion. It was suggested
      that capsule cigarettes, particularly the double capsule cigarette (which had two
      differently flavored capsules in the filter), would encourage nonsmokers to
      experiment with smoking and discourage smokers from quitting. Conclusions: The
      findings offer some reasons behind the global growth of the capsule cigarette
      segment. Implications: Cigarettes with flavor-changing capsules in the filter
      have been one of the most successful product innovations of the last decade for
      tobacco companies. They have received very little academic attention however.
      Employing focus groups with 120 smokers aged 16 and over, we found that capsule
      cigarettes held most appeal to, and were considered to be targeted at, younger
      people, with it suggested that these products would encourage initiation and
      discourage cessation. This study provides some understanding of how these
      products are viewed by smokers.

PMID- 29059393
TI  - Tobacco Use and Socioeconomically Disadvantaged Groups.

PMID- 29059392
TI  - Molecular mechanism of DNA association with single-stranded DNA binding protein.
AB  - During DNA replication, the single-stranded DNA binding protein (SSB) wraps
      single-stranded DNA (ssDNA) with high affinity to protect it from degradation and
      prevent secondary structure formation. Although SSB binds ssDNA tightly, it can
      be repositioned along ssDNA to follow the advancement of the replication fork.
      Using all-atom molecular dynamics simulations, we characterized the molecular
      mechanism of ssDNA association with SSB. Placed in solution, ssDNA-SSB assemblies
      were observed to change their structure spontaneously; such structural changes
      were suppressed in the crystallographic environment. Repeat simulations of the
      SSB-ssDNA complex under mechanical tension revealed a multitude of possible
      pathways for ssDNA to come off SSB punctuated by prolonged arrests at
      reproducible sites at the SSB surface. Ensemble simulations of spontaneous
      association of short ssDNA fragments with SSB detailed a three-dimensional map of
      local affinity to DNA; the equilibrium amount of ssDNA bound to SSB was found to
      depend on the electrolyte concentration but not on the presence of the acidic
      tips of the SSB tails. Spontaneous formation of ssDNA bulges and their diffusive
      motion along SSB surface was directly observed in multiple 10-us-long
      simulations. Such reptation-like motion was confined by DNA binding to high
      affinity spots, suggesting a two-step mechanism for SSB diffusion.

PMID- 29059395
TI  - Moderator's view: High-volume plasma exchange: pro, con and consensus.
AB  - I have been asked to comment on the pro and con opinions regarding high-volume
      plasma exchange. The authors of both positions have provided cogent arguments and
      a reasonable approach to choosing the exchange volume for any given therapeutic
      plasma exchange. The major issue of relevance in this discussion is the nature of
      the toxins targeted for removal. These parameters include molecular weight, the
      apparent volume of distribution, the degree of protein binding, the biologic and
      chemical half-life, and the severity and rapidity of its toxicity.

PMID- 29059394
TI  - Adherence to Pharmacological Smoking Cessation Interventions: A Literature Review
      and Synthesis of Correlates and Barriers.
AB  - Introduction: Efficacious pharmacological interventions for smoking cessation are
      available, but poor adherence to these treatments may limit these interventions
      overall impact. To improve adherence to smoking cessation interventions, it is
      first necessary to identify and understand smoker-level characteristics that
      drive nonadherence (ie, nonconformance with a provider's recommendation of
      timing, dosage, or frequency of medication-taking during the prescribed length of
      time). Methods: We present a literature review of studies examining correlates
      of, or self-reported reasons for, nonadherence to smoking cessation
      pharmacotherapies. Studies were identified through PubMed-using MeSH terms,
      Embase-using Emtree terms, and ISI Web of Science. Results and Conclusions: This
      literature review included 50 studies that examined nonpreventable (eg,
      sociodemographics) and preventable (eg, forgetfulness) factors associated with
      adherence to smoking cessation medication and suggestions for overcoming some of
      the identified barriers. Systematic study of this topic would be facilitated by
      consistent reporting of adherence and correlates thereof in the literature,
      development of consistent definitions of medication adherence across studies,
      utilization of more objective measures of adherence (eg, blood plasma levels vs.
      self-report) in addition to reliance on self-reported adherence. Implications:
      This article provides the most comprehensive review to date on correlates of
      adherence to pharmacological smoking cessation interventions. Challenges and
      specific gaps in the literature that should be a priority for future research are
      discussed. Future priorities include additional research, particularly among
      vulnerable populations of smokers, developing standardized definitions of
      adherence and methods for measuring adherence, regular assessment of cessation
      pharmacotherapy adherence in the context of research and clinical practice, and
      development of novel treatments aimed at preventable barriers to medication
      adherence.

PMID- 29059397
TI  - Pro: High dose of therapeutic plasma exchange-mind the gap!
AB  - 'Mind the gap' is a recorded warning phrase used in the London Tube since 1969.
      The following article is meant to be a warning of an increasing knowing-doing gap
      in routine practice of therapeutic plasma exchange (TPE), a treatment method that
      is used more and more throughout the world. The American Society of Apheresis
      recommendations, including the most recent ones from 2016, suggest using a TPE
      volume of 1.0-1.5 times the actual calculated plasma volume of the patient. There
      are only a few exceptions to that rule, such as the recommnded exchange volume in
      vasculitis or mushroom poisoning. The published literature suggests that in
      routine clinical practice in many institutions in several countries the exchanged
      volume might in fact be lower than recommended by the guidelines. In the
      following article we argue for a high dose of exchanged plasma volume, yet sketch
      different scenarios on how this time-averaged high dose can be delivered in
      various ways depending on the underlying disease, refuting a one-size-fits-all
      strategy that might facilitate the procedure but may result in 'underpheresis' in
      many patients. Further, the objectives underlying the use of smaller exchange
      volumes, especially the gap between the cost of blood products and the
      reimbursement of TPE are discussed. Lastly, the knowing-guiding gap is described,
      which can only be overcome by collecting high-quality data and conducting
      prospective clinical trials in the field of TPE.

PMID- 29059396
TI  - Renal safety of catheter-based renal denervation: systematic review and meta
      analysis.
AB  - Background: Catheter-based renal denervation (RDN) is a possible treatment to
      lower blood pressure. The invasive nature of RDN and the use of contrast agents
      raise concerns about potential consequent kidney damage. Our objective was to
      determine the change in renal function after RDN by performing a systematic
      review on hypertensive patients treated with RDN. Methods: A systematic search
      was performed in the Embase and MEDLINE databases to identify studies reporting
      on the effects of catheter-based RDN on renal outcome. Studies published between
      January 2009 and May 2016, irrespective of study design, device used or
      indication for treatment were included. We performed random effects meta-analyses
      on the change in estimated glomerular filtration rate (eGFR), serum creatinine,
      serum cystatin C and albumin:creatinine ratio after RDN. We only extracted and
      meta-analysed data from patients treated with RDN. Results: From 1034 citations,
      52 studies (38 cohort studies, 4 non-randomized comparative studies and 10
      randomized controlled trials) reporting on 56 RDN cohorts were included in meta
      analyses and another 14 studies in a qualitative review. Of these 56 cohorts, 48
      were specifically eligible for determining the change in eGFR after RDN, totaling
      2381 patients. There was no statistically significant change in eGFR after a mean
      follow-up time of 9.1 +/- 7.0 months [0.64 mL/min/1.73 m 2 (95% confidence
      interval -0.47 to 1.76), P = 0.26]. The pooled mean change in serum creatinine
      and the results of the qualitative review further supported these findings.
      Conclusions: Based on meta-analyses of 52 studies and a qualitative review of an
      additional 14 studies, reporting on 2898 patients in total, we conclude that
      renal function does not significantly change up to at least 9 months after RDN.

PMID- 29059398
TI  - Opponent's comments.

PMID- 29059399
TI  - Con: High-volume plasma exchange application in nephrology and beyond.
AB  - The rationale behind the use of plasma exchange (PE) includes the removal of
      autoantibodies and other plasma constituents, such as cytokines, complement
      components, neutrophil extracellular traps, and microparticles, and the
      substitution of missing plasma factors. The more established indications are
      associated with the beneficial effects of PE of reducing the plasma levels of
      pathogenic agents, although the efficiency of this process decreases during the
      course of the procedure as the substituted replacement fluid dilutes the
      patient's original plasma. Thus, removal can be more effective by repeating
      sessions rather than continuing so-called high-volume PE. The kinetics of PE
      efficiency have been extensively investigated and exchange between body
      compartments of substances to be removed is of considerable importance.

PMID- 29059400
TI  - Opponent's comments.

PMID- 29059401
TI  - Completeness of reporting of adverse events in trials of maintenance
      immunosuppression in kidney transplantation: a systematic review.
AB  - Background: Decision-making regarding immunosuppression after transplantation
      relies on robust evidence on the benefits and harms of available drugs. We aimed
      to evaluate the reporting of adverse events (AEs) in trials of maintenance
      immunosuppression in kidney transplantation. Methods: We conducted a systematic
      review of published randomized controlled trials of maintenance immunosuppression
      following kidney transplantation in the Cochrane Kidney and Transplant Register
      (January 2003-December 2015). Appraisal against the 23-item harms extension of
      the Consolidated Standards of Reporting Trials statement was conducted. Results:
      Of 233 trials, 163 (69%) reported at least one AE. Only 17 (10%) provided
      definitions or justified the AEs, 13 (8%) described methods and 27 (17%) measured
      severity. Forty AE types were reported, with gastrointestinal being the most
      common [116 (71%)]. The frequency of reporting did not reflect known drug side
      effect profiles. For example, of 90 calcineurin inhibitor trials, only 22%
      reported tremors, 3% paresthesia and none anxiety, aggression or mood swings.
      Trials that reported at least one adverse effect were more likely to be industry
      funded {adjusted odds ratio [OR] 7.6 [95% confidence interval (CI) 3.4-17.1]},
      multicenter [OR 5.9 (95% CI 1.7-18.7)] and with follow-up time <24 months [OR 3.7
      (95% CI 1.4-10.2)]. Conclusions: AEs in kidney transplant immunosuppression
      trials appear to be selectively reported and may be unreliable for clinical
      decisions. Adherence to the Consolidated Standards of Reporting Trials harms
      extension should be mandatory to ensure transparent reporting of AEs that are
      important to patients and clinicians.

PMID- 29059402
TI  - Efficacy and safety of nicotinamide in haemodialysis patients: the NICOREN study.

PMID- 29059404
TI  - Catheter-based renal denervation and renal function: no evidence of harm but is
      there a hope of nephroprotection?

PMID- 29059403
TI  - Incidence of hyperglycemia and diabetes and association with electrolyte
      abnormalities in pediatric solid organ transplant recipients.
AB  - Background: Posttransplant hyperglycemia is an important predictor of new-onset
      diabetes after transplantation, and both are associated with significant
      morbidity and mortality. Precise estimates of posttransplant hyperglycemia and
      diabetes in children are unknown. Low magnesium and potassium levels may also
      lead to diabetes after transplantation, with limited evidence in children.
      Methods: We conducted a cohort study of 451 pediatric solid organ transplant
      recipients to determine the incidence of hyperglycemia and diabetes, and the
      association of cations with both endpoints. Hyperglycemia was defined as random
      blood glucose levels >=11.1 mmol/L on two occasions after 14 days of transplant
      not requiring further treatment. Diabetes was defined using the American Diabetes
      Association Criteria. For magnesium and potassium, time-fixed, time-varying and
      rolling average Cox proportional hazards models were fitted to evaluate the
      association with hyperglycemia and diabetes. Results: Among 451 children, 67
      (14.8%) developed hyperglycemia and 27 (6%) progressed to diabetes at a median of
      52 days (interquartile range 22-422) from transplant. Multi-organ recipients had
      a 9-fold [hazard ratio (HR) 8.9; 95% confidence interval (CI) 3.2-25.2] and lung
      recipients had a 4.5-fold (HR 4.5; 95% CI 1.8-11.1) higher risk for hyperglycemia
      and diabetes, respectively, compared with kidney transplant recipients. Both
      magnesium and potassium had modest or no association with the development of
      hyperglycemia and diabetes. Conclusions: Hyperglycemia and diabetes occur in 15
      and 6% children, respectively, and develop early posttransplant with lung or
      multi-organ transplant recipients at the highest risk. Hypomagnesemia and
      hypokalemia do not confer significantly greater risk for hyperglycemia or
      diabetes in children.

PMID- 29059405
TI  - Vasculitis-when can biopsy be avoided?

PMID- 29059406
TI  - Dynamic site-specific recruitment of RBP2 by pocket protein p130 modulates H3K4
      methylation on E2F-responsive promoters.
AB  - The Histone 3 lysine 4 methylation (H3K4me3) mark closely correlates with active
      transcription. E2F-responsive promoters display dynamic changes in H3K4
      methylation during the course of cell cycle progression. However, how and when
      these marks are reset, is not known. Here we show that the retinoblastoma binding
      protein RBP2/KDM5A, capable of removing tri-methylation marks on H3K4, associates
      with the E2F4 transcription factor via the pocket protein-p130-in a cell-cycle
      stage specific manner. The association of RBP2 with p130 is LxCxE motif
      dependent. RNAi experiments reveal that p130 recruits RBP2 to E2F-responsive
      promoters in early G1 phase to bring about H3K4 demethylation and gene
      repression. A point mutation in LxCxE motif of RBP2 renders it incapable of p130
      interaction and hence, repression of E2F-regulated gene promoters. We also
      examine how RBP2 may be recruited to non-E2F responsive promoters. Our studies
      provide insight into how the chromatin landscape needs to be adjusted rapidly and
      periodically during cell-cycle progression, concomitantly with temporal
      transcription, to bring about expression/repression of specific gene sets.

PMID- 29059407
TI  - State-Level Support for Tobacco 21 Laws: Results of a Five-State Survey.
AB  - Introduction: Legal strategies to raise the minimum age of purchase for tobacco
      from 18 to 21, known as "Tobacco 21 laws" are a promising means to reduce
      adolescent tobacco initiation and use. Tobacco 21 laws are enacted at the local
      and state level, yet prior studies have examined national support. To address
      this gap, we assessed attitudes of residents in five states toward Tobacco 21
      laws, and how attitudes varied by demographic, political, and health status
      characteristics. Methods: The data are derived from the 2016 Texas Medical Center
      (TMC) Consumer Health Report, a survey of 5007 adults from five states:
      California, Florida, Ohio, New York, and Texas. Bivariate and multivariate
      logistic regression analyses were used to assess differences in support. Results:
      Eight in 10 respondents supported Tobacco 21. Support was high across all five
      states, ranging from 78% in Texas to 85% in New York. Tobacco 21 was supported by
      a majority of respondents in all racial, educational, age, and income groups
      assessed. While support was generally strong, chi-square analyses revealed
      differences across states in support by demographic and health status
      characteristics. Support was generally higher among older individuals, whites,
      and those with more education, although the size and even direction of the
      relationship by population subgroup varied across states. Conclusion: Tobacco 21
      laws enjoy overwhelming majority support in all five states and across all
      sociodemographic subgroups assessed. However, the strength of support by
      population subgroup varies across states. Implications: While earlier studies had
      found strong support for Tobacco 21 laws at the national level, little data were
      available about attitudes at the state level, where current Tobacco 21
      policymaking efforts are concentrated. Our data indicate that legislators from
      both liberal and conservative states should feel confident in advancing Tobacco
      21 laws to protect the current and future health of adolescents. However,
      patterns of support vary by population subgroup across states. Understanding
      variations in support by population subgroup at the state level can guide
      policymakers in targeted efforts to advance public health laws aimed at reducing
      adolescent tobacco initiation and use.

PMID- 29059408
TI  - PopHuman: the human population genomics browser.
AB  - The 1000 Genomes Project (1000GP) represents the most comprehensive world-wide
      nucleotide variation data set so far in humans, providing the sequencing and
      analysis of 2504 genomes from 26 populations and reporting >84 million variants.
      The availability of this sequence data provides the human lineage with an
      invaluable resource for population genomics studies, allowing the testing of
      molecular population genetics hypotheses and eventually the understanding of the
      evolutionary dynamics of genetic variation in human populations. Here we present
      PopHuman, a new population genomics-oriented genome browser based on JBrowse that
      allows the interactive visualization and retrieval of an extensive inventory of
      population genetics metrics. Efficient and reliable parameter estimates have been
      computed using a novel pipeline that faces the unique features and limitations of
      the 1000GP data, and include a battery of nucleotide variation measures,
      divergence and linkage disequilibrium parameters, as well as different tests of
      neutrality, estimated in non-overlapping windows along the chromosomes and in
      annotated genes for all 26 populations of the 1000GP. PopHuman is open and freely
      available at http://pophuman.uab.cat.

PMID- 29059409
TI  - Facilitated Extinction Training to Improve Pharmacotherapy for Smoking Cessation:
      A Pilot Feasibility Trial.
AB  - Introduction: Varenicline reduces smoking satisfaction during the pre-cessation
      run-in period, which may contribute to extinction of cravings and smoking
      behavior. Research indicates that efficacy is enhanced when the run-in period is
      increased from 1 to 4 weeks, providing a longer extinction opportunity. We
      hypothesized that efficacy could be further enhanced by harnessing basic and
      applied research on extinction. We developed a pre-cessation extinction
      facilitating intervention and tested its feasibility in a pilot trial. Methods:
      The facilitated extinction (FE) intervention comprised brief counseling and
      workbook-recommending strategies to maximize extinction processes during the run
      in, including instructions to smoke at a normal rate across contexts and cues,
      and use of an extinction cue to enhance generalization. Participants were
      randomly assigned to one of three varenicline interventions: standard (1-week run
      in), extended (4-week run-in), and extended + FE. Interventions were delivered
      prior to the target quit date (TQD). Assessments were conducted in weeks 1 and 4
      pre-TQD and 1 and 3 months post-TQD, with focus on feasibility indices. Results:
      Recruitment and retention goals were met (N = 58). Treatment satisfaction was
      high across groups. The majority of FE participants adhered to instructions and
      maintained their usual smoking rate during the run-in period. Greater decreases
      in craving and smoking satisfaction were observed among participants in both
      extended groups versus the standard group (p < .005). Conclusions: Feasibility
      was demonstrated. Participants adhered to the FE intervention, thereby optimizing
      the number and variety of extinction trials. Findings support testing the novel
      FE smoking cessation intervention in a fully powered trial. Implications: This
      study expands the research on the clinical benefits of extending the pre
      cessation run-in period of varenicline. It introduces the hypothesis that further
      benefit might be achieved by translating basic behavioral research, as well as
      cue-exposure research and therapy for other disorders, to improve the extinction
      and generalization processes thought to underlie much of varenicline's effect. A
      FE intervention was developed and found acceptable to smokers and feasible to
      implement in a research setting. The study sets the stage for a subsequent
      randomized controlled trial.

PMID- 29059411
TI  - Clinical and Laboratory Factors Associated with Severe Dengue: A Case-Control
      Study of Hospitalized Children.
AB  - Background: More than half of the hospitalizations because of dengue in Brazil
      occurred in children <15 years of age in 2007 and 2008, an unexpected change in
      the epidemiological pattern. We sought to determine clinical and laboratory
      parameters associated with severity. Methods: A case-control study was conducted
      in three pediatric hospitals in Rio de Janeiro, Brazil; 233 laboratory-confirmed
      dengue patients were included: 69 cases and 164 controls. Specific clinical and
      laboratory factors were assessed using univariate and multivariate logistic
      regression models. Results: Lethargy [adjusted odds ratio (ORa): 9.15, 95%
      confidence interval (CI): 3.08-27.12], dyspnea (ORa: 8.24, 95% CI: 3.27-20.72)
      and abdominal pain (ORa: 6.78, 95% CI: 1.44-31.84) were independently associated
      with severe dengue in children. Lethargy and dyspnea presented as early as 72 and
      48 h, respectively, before shock. Conclusions: Abdominal pain and lethargy
      confirmed their role as warning signs, which along with dyspnea might be helpful
      in identifying cases progressing to severe dengue.

PMID- 29059410
TI  - Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female
      Adult Smokers: A Preliminary Study.
AB  - Background: The goal of this study was to conduct a preliminary network analysis
      (using graph-theory measures) of intrinsic functional connectivity in adult
      smokers, with an exploration of sex differences in smokers. Methods: Twenty-seven
      adult smokers (13 males; mean age = 35) and 17 sex and age-matched controls (11
      males; mean age = 35) completed a blood oxygen level-dependent resting state
      functional magnetic resonance imaging experiment. Data analysis involved
      preprocessing, creation of connectivity matrices using partial correlation, and
      computation of graph-theory measures using the Brain Connectivity Toolbox.
      Connector hubs and additional graph-theory measures were examined for differences
      between smokers and controls and correlations with nicotine dependence. Sex
      differences were examined in a priori regions of interest based on prior
      literature. Results: Compared to nonsmokers, connector hubs in smokers emerged
      primarily in limbic (parahippocampus) and salience network (cingulate cortex)
      regions. In addition, global influence of the right insula and left nucleus
      accumbens was associated with higher nicotine dependence. These trends were
      present in male but not female smokers. Conclusions: Network communication was
      altered in smokers, primarily in limbic and salience network regions. Network
      topology was associated with nicotine dependence in male but not female smokers
      in regions associated with reinforcement (nucleus accumbens) and craving
      (insula), consistent with the idea that male smokers are more sensitive to the
      reinforcing aspects of nicotine than female smokers. Implications: Identifying
      alterations in brain network communication in male and female smokers can help
      tailor future behavioral and pharmacological smoking interventions. Male smokers
      showed alterations in brain networks associated with the reinforcing effects of
      nicotine more so than females, suggesting that pharmacotherapies targeting
      reinforcement and craving may be more efficacious in male smokers.

PMID- 29059412
TI  - Barriers to Using Nonpharmacologic Approaches and Reducing Opioid Use in Primary
      Care.
AB  - Background: Opioid prescribing for chronic pain, including the potential for over
      reliance and misuse, is a public health concern. Objective: In the context of
      Veterans Administration (VA) primary care team-based pain management, we aimed to
      understand providers' perceptions of barriers to reducing opioid use and
      improving the use of nonpharmacologic pain management therapies (NPTs) for
      chronic pain. Design: A semistructured interview elucidated provider experiences
      with assessing and managing pain. Emergent themes were mapped to known dimensions
      of VA primary care access. Subjects: Informants included 60 primary care
      providers, registered nurses, licensed practical nurses, clerks, psychologists,
      and social workers at two VA Medical Centers. Methods: Nine multidisciplinary
      focus groups. Results: Provider perceptions of barriers to reducing opioids and
      improving use of NPTs for patients with chronic pain clustered around
      availability and access. Barriers to NPT access included the following subthemes:
      geographical (patient distance from service), financial (out-of-pocket cost to
      patient), temporal (treatment time delays), cultural (belief that NPTs increased
      provider workload, perception of insufficient training on NPTs, perceptions of
      patient resistance to change, confrontation avoidance, and insufficient
      leadership support), and digital (measure used for pain assessment, older
      patients hesitant to use technology, providers overwhelmed by information).
      Conclusions: Decreasing reliance on opioids for chronic pain requires a
      commitment to local availability and provider-facing strategies that increase
      efficacy in prescribing NPTs. Policies and interventions for decreasing
      utilization of opioids and increasing use of NPTs should comprehensively consider
      access barriers.

PMID- 29059413
TI  - The Time-Varying Relations Between Risk Factors and Smoking Before and After a
      Quit Attempt.
AB  - Introduction: Intensive longitudinal data (ILD) collected with ecological
      momentary assessments (EMAs) can provide a rich resource for understanding the
      relations between risk factors and smoking in the time surrounding a cessation
      attempt. Methods: Participants (N = 142) were smokers seeking treatment at a
      safety-net hospital smoking cessation clinic who were randomly assigned to
      receive standard clinic care (ie, counseling and cessation medications) or
      standard care plus small financial incentives for biochemically confirmed smoking
      abstinence. Participants completed EMAs via study provided smartphones several
      times per day for 14 days (1 week prequit through 1 week postquit). EMAs assessed
      current contextual factors including environmental (eg, easy access to
      cigarettes, being around others smoking), cognitive (eg, urge to smoke, stress,
      coping expectancies, cessation motivation, cessation self-efficacy,
      restlessness), behavioral (ie, recent smoking and alcohol consumption), and
      affective variables. Temporal relations between risk factors and smoking were
      assessed using a logistic time-varying effect model. Results: Participants were
      primarily female (57.8%) and Black (71.8%), with an annual household income of
      <$20000 per year (71.8%), who smoked 17.6 cigarettes per day (SD = 8.8).
      Individuals assigned to the financial incentives group had decreased odds of
      smoking compared with those assigned to usual care beginning 3 days before the
      quit attempt and continuing throughout the first week postquit. Environmental,
      cognitive, affective, and behavioral variables had complex time-varying impacts
      on smoking before and after the scheduled quit attempt. Conclusions: Knowledge of
      time-varying effects may facilitate the development of interventions that target
      specific psychosocial and behavioral variables at critical moments in the weeks
      surrounding a quit attempt. Implications: Previous research has examined time
      varying relations between smoking and negative affect, urge to smoke, smoking
      dependence, and certain smoking cessation therapies. We extend this work using
      ILD of unexplored variables in a socioeconomically disadvantaged sample of
      smokers seeking cessation treatment. These findings could be used to inform
      ecological momentary interventions that deliver treatment resources (eg, video-
      or text-based content) to individuals based upon critical variables surrounding
      their attempt.

PMID- 29059414
TI  - Nicotine Metabolism in Adults with Type 2 Diabetes.
AB  - Introduction: Metabolism of nicotine has implications for addiction and may be
      altered in people with type 2 diabetes. Thus, our objective was to analyze
      nicotine metabolism in adults with and without type 2 diabetes who smoke.
      Methods: From an existing cross-sectional study, we analyzed nicotine metabolism
      in urine of 148 smokers, 36 type 2 diabetics (insulin or antidiabetic medication
      use and/or fasting glucose >126 mg/dL), and 112 non-diabetics. Nicotine
      metabolism was quantified as the nicotine metabolite ratio (NMR) = trans-3'
      hydroxycotinine (3HC) divided by COT. COT and 3HC were measured in the
      participant urine by ultra-performance liquid chromatography tandem mass
      spectrometry (UPLC MS-MS). Generalized linear models were used to assess whether
      NMR was associated with diabetic status (yes/no). Results: Participants
      categorized as high NMR smoked more cigarettes per day (p=0.002) and were more
      likely to be diabetic (p=0.022) compared to low NMR. We found no significant
      difference in total nicotine equivalents (TNE) defined as the sum of the
      nicotine, COT and 3HC (p>0.05). In unadjusted models, NMR was 42.5% higher in
      diabetics versus non-diabetics (95% CI: 12.9, 79.8; p=0.003). In models adjusted
      for factors significantly different between low versus high NMR participants,
      mean NMR was 36.5% higher in the diabetics versus non-diabetics (95% CI: 7.8,
      72.8; p=0.010). Additionally, in models adjusted for known confounders of NMR,
      NMR was 40.6% higher in diabetics versus non-diabetics (95% CI: 9.9, 80.0;
      p=0.007). Conclusions: From these data, we infer that type 2 diabetics metabolize
      nicotine faster, which may increase the potential for nicotine addiction.
      IMPLICATIONS: Smoking is addictive and this addiction may be related to tobacco
      metabolism. Individuals with faster metabolism of nicotine tend to smoke more
      cigarettes for longer periods of time. People with type 2 diabetes may metabolize
      nicotine faster, which could lead to higher lifetime tobacco burden, increasing
      the adverse health outcomes associated with increased exposure to tobacco.

PMID- 29059415
TI  - Frequency and Content of Conversations About Pictorial Warnings on Cigarette
      Packs.
AB  - Introduction: Social interactions are a key mechanism through which health
      communication efforts, including pictorial cigarette pack warnings, may exert
      their effects. We sought to better understand social interactions elicited by
      pictorial cigarette pack warnings. Methods: A controlled trial randomly assigned
      US adult smokers (n = 2149) to have their cigarette packs labeled with pictorial
      or text-only warnings for 4 weeks. Smokers completed surveys during the baseline
      visit and each of the subsequent 4 weekly visits. Results: Smokers with pictorial
      warnings on their packs had more conversations throughout the trial compared to
      those with text-only warnings (8.2 conversations vs 5.0, p<.01). The highest
      number of conversations occurred during the first week. Smokers with pictorial
      warnings were more likely than those with text-only warnings to discuss the
      health effects of smoking, whether the warnings would make them want to quit and
      whether the warnings would make others want to quit (all p < .05). Smokers were
      more likely to describe pictorial warnings as scary, gross, or depressing and
      gloomy during conversations than text-only warnings (all p < .05). Conclusions:
      Pictorial warnings sparked more conversations about the warnings, the health
      effects of smoking, and quitting smoking than text-only warnings. These social
      interactions may extend the reach of pictorial warnings beyond the targeted
      smoker and may be one of the processes by which pictorial warnings have impact.
      Implications: Health communication can influence behavior by changing social
      interactions. Our trial characterized social interactions about pictorial
      cigarette pack warnings with a large longitudinal sample in a real-world setting.
      Understanding these conversations can inform the United States and other
      countries as they improve existing warnings and help tobacco control policy
      makers and health communication theorists understand how social interactions
      triggered by warnings affect smoking.

PMID- 29059416
TI  - Examining Daily Electronic Cigarette Puff Topography Among Established and
      Nonestablished Cigarette Smokers in their Natural Environment.
AB  - Introduction: Understanding exposures and potential health effects of e
      cigarettes is complex. Users' puffing behavior, or topography, affects function
      of e-cigarette devices (eg, coil temperature) and composition of their emissions.
      Users with different topographies are likely exposed to different amounts of any
      harmful or potentially harmful constituents (HPHCs). In this study, we compare e
      cigarette topographies of established cigarette smokers and nonestablished
      cigarette smokers. Methods: Data measuring e-cigarette topography were collected
      using a wireless hand-held monitoring device in users' everyday lives over 1
      week. Young adult (aged 18-25) participants (N = 20) used disposable e-cigarettes
      with the monitor as they normally would and responded to online surveys.
      Topography characteristics of established versus nonestablished cigarette smokers
      were compared. Results: On average, established cigarette smokers in the sample
      had larger first puff volume (130.9 mL vs. 56.0 mL, p < .05) and larger puff
      volume per session (1509.3 mL vs. 651.7 mL, p < .05) compared with nonestablished
      smokers. At marginal significance, they had longer sessions (566.3 s vs. 279.7 s,
      p = .06) and used e-cigarettes more sessions per day (5.3 s vs. 3.5 s, p = .14).
      Established cigarette smokers also used e-cigarettes for longer puff durations
      (3.3 s vs. 1.8 s, p < .01) and had larger puff volume (110.3 mL vs. 54.7 mL, p <
      .05) compared with nonestablished smokers. At marginal significance, they had
      longer puff interval (38.1 s vs. 21.7 s, p = .05). Conclusions: Our results
      demonstrate that topography characteristics differ by level of established
      cigarette smoking. This suggests that exposure to constituents of e-cigarettes
      depends on user characteristics and that specific topography parameters may be
      needed for different user populations when assessing e-cigarette health effects.
      Implications: A user's topography affects his or her exposure to HPHCs. As this
      study demonstrates, user characteristics, such as level of smoking, can influence
      topography. Thus, it is crucial to understand the topography profiles of
      different user types to assess the potential for population harm and to identify
      potentially vulnerable populations. This study only looked at topography of
      cigarette smokers using disposable e-cigarettes. Further research is needed to
      better understand potential variation in e-cigarette topography and resulting
      exposures to HPHCs among users of different e-cigarette devices and liquids.

PMID- 29059417
TI  - Brief Web-Based Interventions for Young Adult Smokers With Severe Mental
      Illnesses: A Randomized, Controlled Pilot Study.
AB  - Significance: About 50% of young adults with schizophrenia, bipolar disorder, and
      other severe mental illnesses smoke tobacco, but few studies have evaluated
      interventions for this group. Methods: We conducted a randomized pilot study
      among 58 young adult smokers with severe mental illnesses comparing a brief
      interactive web-based motivational tool, Let's Talk About Smoking, to
      computerized standard education from the National Cancer Institute. An additional
      23 subjects received minimal tobacco assessment at baseline and no intervention,
      providing a comparison condition for naturalistic cessation behavior. All
      participants (total n = 81) were assessed for smoking and breath carbon monoxide
      at baseline and 14 weeks and had access to standard cessation treatments.
      Results: The 81 participants were stable outpatients ages 18-30 (mean 24.8
      years): 43.2% were diagnosed with schizophrenia-spectrum disorders, the remainder
      with severe mood and anxiety disorders. They smoked 14.6 +/- 10.2 cigarettes per
      day. All participants completed their assigned intervention; 83.4% of Let's Talk
      About Smoking users and 71.4% of standard education users rated their
      intervention "good" or "very good." At 14 weeks, less than 15% of participants in
      all conditions had used additional cessation treatment. Let's Talk About Smoking
      users were more likely to have biologically verified abstinence at 14 weeks than
      standard education users (14.8% vs. 0%; X2 = 3.7, p = .05). None of the
      participants in the naturalistic comparison condition were abstinent at 14 weeks.
      Conclusions: Interactive, web-based motivational interventions are feasible and
      promising for smoking cessation among young smokers with severe mental illnesses.
      Such interventions warrant further study among this group of smokers.
      Implications: Young adult smokers with severe mental illnesses are a vulnerable
      population that, without intervention, goes on to experience disparate morbidity
      and mortality. Brief, easily disseminable interventions are needed to facilitate
      cessation in this group. This pilot research indicates that brief, technology
      delivered, motivational interventions that are tailored for this group may be
      able to activate a significant number to quit without additional cessation
      intervention.

PMID- 29059418
TI  - Differences in Adolescent E-cigarette and Cigarette Prevalence in Two Policy
      Environments: South Korea and the United States.
AB  - Introduction: In the context of different regulatory environments, different
      patterns of e-cigarette use have emerged among adolescents worldwide. The United
      States and South Korea are two examples, the latter of which has maintained much
      more extensive regulation of e-cigarettes. Methods: This analysis compares the
      prevalence of e-cigarette and conventional cigarette use between 2011 and 2015
      from the Korean Youth Risk Behavior Web-based Survey and the U.S. National Youth
      Tobacco Survey, both nationally representative samples of middle and high school
      students that use similar questions. Results: E-cigarette prevalence (past 30
      days) among South Korean adolescents decreased from 4.7% in 2011 (95% confidence
      interval [CI]: 4.4-5.0) to 4.0% (3.7-4.3) in 2015 but increased dramatically
      among US adolescents from 0.9% (0.7-1.2) to 11.2% (9.9-12.7). Cigarette
      prevalence (past 30 days) decreased in South Korea from 12.1% (11.6-12.7) to 7.8%
      (CI: 7.3-8.3) and in the United States from 11.1% (9.5-12.6) to 6.1% (5.1-7.3).
      Combined prevalence of cigarette and e-cigarette use (adjusting for dual users)
      decreased in South Korea from 13.2% (12.7-13.8) to 8.5% (8.0-9.1) but increased
      in the United States from 11.3% (9.7-12.9) to 14.0% (12.4-15.7). Conclusions: In
      South Korea, where e-cigarettes are extensively regulated, adolescent e-cigarette
      use remained stable at a low level, whereas in the United States, where e
      cigarette regulation has been limited, e-cigarette use increased. Combined e
      cigarette plus cigarette use declined in South Korea whereas it increased in the
      United States. The restrictive policies in South Korea likely contributed to
      lower overall product use. Implications: This paper compared the strength of
      regulation of South Korea and the United States with the prevalence of
      adolescents' e-cigarette and cigarette use and suggests that more restrictive
      policies likely to contribute to lower e-cigarette use and overall use of e
      cigarette and cigarette.

PMID- 29059419
TI  - A Meta-Analysis of Brief Tobacco Interventions for Use in Integrated Primary
      Care.
AB  - Introduction: The integration of behavioral health services in primary care
      settings presents an opportunity to enhance the delivery of tobacco cessation
      interventions in the primary care setting, but guidance on evidence-based
      treatments for tobacco use disorder that fits the brief format of integrated
      primary care (IPC) is limited. This meta-analysis summarizes the outcomes of
      brief behavioral interventions targeting tobacco use that can be delivered in IPC
      settings. Methods: A literature search was conducted to locate empirical studies
      examining tobacco cessation interventions that could be implemented in an IPC
      setting. A random effects meta-analytic approach was utilized with odds ratios as
      the effect size. Subgroup analyses were conducted to determine the extent to
      which a number of study, participant, and intervention characteristics affected
      treatment outcome. Results: A total of 36 studies were included (n = 12975
      patients). Patients in the intervention groups exhibited significantly greater
      odds of smoking cessation compared with those in the comparison groups (OR =
      1.78, p < .001). Subgroup analyses did not reveal significant sources of
      heterogeneity attributable to moderators such as methodological quality, gender,
      bioverification, follow-up time period, or intervention characteristics (such as
      setting, type, or length of intervention). Conclusions: Brief tobacco cessation
      interventions that can be delivered in IPC settings were found to be effective.
      Future research in this area might evaluate ways to improve the dissemination and
      implementation of these types of interventions in IPC settings. Implications: The
      integration of behavioral health services into primary care presents a unique
      opportunity to increase the delivery of tobacco cessation interventions, as
      behavioral health providers in these settings are experts in behavior change
      interventions and may have more time to deliver these interventions than primary
      care providers. Results from the current meta-analysis demonstrate that brief
      tobacco cessation interventions that can be implemented in the IPC setting are
      effective. Future research in this area might examine ways to improve the
      dissemination and implementation of brief interventions for tobacco use in IPC
      settings.

PMID- 29059421
TI  - Erratum.

PMID- 29059420
TI  - Changes in Self-Reported Smokefree Workplace Policy Coverage Among Employed
      Adults-United States, 2003 and 2010-2011.
AB  - Introduction: The workplace is a major source of exposure to secondhand smoke
      from combustible tobacco products. Smokefree workplace policies protect
      nonsmoking workers from secondhand smoke and help workers who smoke quit. This
      study examined changes in self-reported smokefree workplace policy coverage among
      U.S. workers from 2003 to 2010-2011. Methods: Data came from the 2003 (n =
      74,728) and 2010-2011 (n = 70,749) waves of the Tobacco Use Supplement to the
      Current Population Survey. Among employed adults working indoors, a smokefree
      workplace policy was defined as a self-reported policy at the respondent's
      workplace that did not allow smoking in work areas and public/common areas.
      Descriptive statistics were used to assess smokefree workplace policy coverage at
      two timepoints overall, by occupation, and by state. Results: The proportion of
      U.S. workers covered by smokefree workplace policies increased from 77.7% in 2003
      to 82.8% in 2010-2011 (p < .00001). The proportion of workers reporting smokefree
      workplace policy coverage increased in 21 states (p < .001) and decreased in two
      states (p < .001) over this period. In 2010-2011, by occupation, this proportion
      ranged from 74.3% for blue collar workers to 84.9% for white collar workers; by
      state, it ranged from 63.3% in Nevada to 92.6% in Montana. Conclusions: From 2003
      to 2010-2011, self-reported smokefree workplace policy coverage among indoor
      adult workers increased nationally, and occupational coverage disparities
      narrowed. However, coverage remained unchanged in half of states, and disparities
      persisted across occupations and states. Accelerated efforts are warranted to
      ensure that all workers are protected by smokefree workplace policies.
      Implications: This study assessed changes in the proportion of indoor workers
      reporting being covered by smokefree workplace policies from 2003 to 2010-2011
      overall and by occupation and by state, using data from the Tobacco Use
      Supplement to the Current Population Survey. The findings indicate that smokefree
      workplace policy coverage among U.S. indoor workers has increased nationally,
      with occupational coverage disparities narrowing. However, coverage remained
      unchanged in half of states, and disparities persisted across occupations and
      states. Accelerated efforts are warranted to ensure that all workers are
      protected by smokefree workplace policies.

PMID- 29059422
TI  - Reversal of Nicotine Withdrawal Signs Through Positive Allosteric Modulation of
      alpha4beta2 Nicotinic Acetylcholine Receptors in Male Mice.
AB  - Introduction: Nicotine withdrawal symptoms are important factors in determining
      the relapse rate to tobacco smoking and drugs that diminish these symptoms would
      potentially have a higher success rate as smoking cessation aids. Unlike US Food
      and Drug administration approved smoke cessation aids (nicotine and varenicline)
      which act as nicotinic acetylcholine receptors (nAChRs) agonists,
      desformylflustrabromine (dFBr) acts as a nAChR positive allosteric modulator with
      higher selectivity to the alpha4beta2 nAChR. In animal studies, dFBr was well
      tolerated and reduced intravenous nicotine self-administration. In this study, we
      use behavioral test in mouse model of spontaneous nicotine withdrawal to assess
      the effect of dFBr on nicotine withdrawal symptoms. Methods: Spontaneous nicotine
      withdrawal in nicotine-dependent ICR male mice was established 18-24 h after
      termination (minipump removal) of 14 days infusion of nicotine. After that (day
      15), spontaneous signs of nicotine withdrawal were examined in the following
      order: anxiety-like behaviors, somatic signs, and then hyperalgesia using
      previously published behavioral protocols. Fifteen minutes before withdrawal
      signs testing, mice received a subcutaneous acute injection of vehicle or dFBr at
      the doses of 0.02, 0.1, and 1 mg/kg to determine the effect of dFBr on nicotine
      withdrawal symptoms. Results: dFBr produced dose-dependent reversal of nicotine
      withdrawal signs in mouse model of spontaneous nicotine withdrawal. Implications:
      Positive allosteric modulators of nAChR such as dFBr reduce nicotine withdrawal
      symptoms supporting the potential clinical use of this novel class of nAChR-based
      therapeutics as smoking cessation aid.

PMID- 29059423
TI  - US Adult Cigar Smoking Patterns, Purchasing Behaviors, and Reasons for Use
      According to Cigar Type: Findings From the Population Assessment of Tobacco and
      Health (PATH) Study, 2013-2014.
AB  - Introduction: The US cigar market is diverse, yet until recently most research
      studies and tobacco surveillance systems have not reported behavioral and related
      outcomes by cigar type. Methods: The 2013-2014 Population Assessment of Tobacco
      and Health Study collected data separately for filtered cigars (FCs), cigarillos,
      and traditional cigars, which were further distinguished as premium or
      nonpremium. Descriptive statistics for adult established current smokers of each
      cigar type and cigarettes were calculated for demographic characteristics,
      tobacco use patterns, purchasing behaviors and reasons for use. Adjusted
      prevalence ratios (APRs) using a marginal predictions approach with logistic
      regression assessed correlates of dual cigar and cigarette smoking. Results: Age,
      sex, race/ethnicity, education level, and poverty status of smokers varied
      according to cigar type. Daily cigar smoking prevalence and number of cigars
      smoked per day were higher for FCs (37.3%; median: 1.6 cigars/day, respectively),
      than all other cigar types (6.7%-25.3%, all p < .01; 0.1-0.4 cigars/day, all p <
      .01, respectively); daily smoking and cigars per day were similar for nonpremium
      cigars and cigarillos (p = .11; p = .33, respectively). Cigarette smoking was
      twice as common among smokers of nonpremium cigars, cigarillos, and FCs (58.0%
      66.0%) than among premium cigars (29.9%). Among current cigar smokers, FC smokers
      (APR = 1.23, 95% confidence interval [CI] = 1.09-1.39), other tobacco product
      users (APR = 1.27, 95% CI = 1.15-1.41), and those with a GED/high school diploma
      or less (APR = 1.20, 95% CI = 1.09-1.33) were more likely to also smoke
      cigarettes. Conclusion: User characteristics, cigar smoking patterns, and dual
      smoking with cigarettes varied by cigar type highlighting the importance of
      adequately describing the cigar type studied and, where appropriate,
      differentiating results by cigar type. Implications: Despite the diversity of the
      cigar market place, historically many research studies and tobacco surveillance
      systems have treated cigars as a single product type. This study describes
      similarities and differences in the user characteristics, tobacco use patterns,
      and purchasing behaviors of premium, nonpremium, cigarillo, and filtered cigar
      smokers. To enhance tobacco regulatory science, sufficient descriptions of the
      cigar type(s) studied and, where appropriate, differentiation of the particular
      cigar type(s) studied should be undertaken to improve the interpretation of study
      findings, understanding of cigar use patterns and related behaviors and future
      approaches to reducing cigar-attributable morbidity and mortality.

PMID- 29059424
TI  - HIV Care Initiation: A Teachable Moment for Smoking Cessation?
AB  - Introduction: Tobacco use among persons living with HIV represents an important
      risk factor for poor treatment outcomes, morbidity, and mortality. Thus, efforts
      designed to inform the development of appropriate smoking cessation programs for
      this population remains a public health priority. To address this need, a study
      was conducted to longitudinally assess the relationship between intention to quit
      smoking and cessation over the 12-month period following initiation of HIV care.
      Methods: Patients initiating HIV care at a large inner city safety net clinic
      were enrolled (n = 378) in a 12-month prospective study. Audio computer-assisted
      self-interviews were conducted at baseline, and at 3, 6, 9, and 12 months post
      enrollment, and HIV-related clinical data were collected from participants'
      electronic medical records. Variables of interest included intention to quit
      smoking, 7-day point prevalence smoking abstinence (biochemically verified), and
      stage of HIV. Data were collected in Houston, Texas from 2009 to 2015. Results:
      The sample was 75% male and 62% Black. Findings indicated that intention to quit
      smoking increased between baseline and 3 months, and subsequently trended
      downward from 3 to 12 months. Results from linear and generalized linear mixed
      models indicated that participants with advanced HIV disease (vs. not advanced)
      reported significantly (p < .05) higher intention to quit smoking at 3, 6, and 12
      months post-study enrollment. A similar though nonsignificant pattern was
      observed in the smoking abstinence outcome. Conclusions: HIV treatment initiation
      appears to be associated with increases in intention to quit smoking thus serves
      as a potential teachable moment for smoking cessation intervention. Implications:
      This study documents significant increases in intention to quit smoking in the 3
      month period following HIV care initiation. Moreover, quit intention trended
      downward following the 3-month follow-up until the 12-month follow-up. In
      addition, a marked effect for HIV disease stage was observed, whereby
      participants with advanced HIV disease (vs. those without) experienced a greater
      increase in intention to quit. HIV treatment initiation appears to be associated
      with increases in intention to quit smoking, thus serves as a crucial teachable
      moment for smoking cessation intervention for people living with HIV.

PMID- 29059425
TI  - Snus and Snuff Use in Switzerland Among Young Men: Are There Beneficial Effects
      on Smoking?
AB  - Introduction: There are few recent longitudinal studies on smokeless tobacco
      (SLT) products and smoking outside the United States or European Nordic
      countries. The present longitudinal study tests whether Swedish-type snus and
      nasal snuff use decreases smoking incidence and prevalence in a central European
      country. Methods: The sample consisted of 5198 Swiss men (around 20 years of
      age). Retention rate was 91.5% over 15 months. Regression models, adjusting for a
      variety of psychosocial, smoking-related, and other risk factors, assessed
      whether no, low (less than weekly), and high (weekly or more) use baseline groups
      showed changes or maintenance in snus and snuff use related to smoking
      initiation, cessation, and reduction. Results: Among baseline nonsmokers, snus
      initiators (OR = 1.90, p = .003) and low baseline maintainers (OR = 4.51, p <
      .001) were more likely to start smoking (reference: persistent nonusers of snus).
      Among baseline smokers, initiators (OR = 2.79, p < .001) and low baseline
      maintainers (OR = 2.71, p = .005) more often continued smoking, whereas snus
      quitters less frequently continued smoking (OR = 0.57, p = .009). High baseline
      maintainers were non-significantly less likely to continue smoking (OR = 0.71, p
      = .315). Among continuing smokers, only snus quitters significantly reduced the
      number of cigarettes smoked per day (b = -1.61, p = .002) compared with
      persistent nonusers of snus. Results were similar for snuff. Conclusions: SLT use
      did not have any significant beneficial effects on young men in Switzerland but
      significantly increased the likelihood of smoking initiation and continuation,
      independent of whether the substance is legally sold (snuff) or not (snus). This
      does not exclude that there may be beneficial effects at older ages.
      Implications: Our research provides evidence that SLT use has no benefits for
      cigarette smoking initiation, cessation, or reduction among young men in a
      central European country, where SLT is not highly promoted or receives tax
      incentives. This is true for both legally sold nasal snuff and Swedish-type snus
      that cannot be legally sold. Results indicate that without incentives for using
      it, among young people shifts from smoking to SLT use are questionable and
      confirms the need for country-specific studies before the global public health
      community engages in promoting SLT.

PMID- 29059427
TI  - Microvascular Density as a Predictive Biomarker for Bevacizumab Survival Benefit
      in Ovarian Cancer: Back to First Principles?

PMID- 29059426
TI  - Tumor Microvessel Density as a Potential Predictive Marker for Bevacizumab
      Benefit: GOG-0218 Biomarker Analyses.
AB  - Background: Combining bevacizumab with frontline chemotherapy statistically
      significantly improved progression-free survival (PFS) but not overall survival
      (OS) in the phase III GOG-0218 trial. Evaluation of candidate biomarkers was an
      exploratory objective. Methods: Patients with stage III (incompletely resected)
      or IV ovarian cancer were randomly assigned to receive six chemotherapy cycles
      with placebo or bevacizumab followed by single-agent placebo or bevacizumab. Five
      candidate tumor biomarkers were assessed by immunohistochemistry. The biomarker
      evaluable population was categorized into high or low biomarker-expressing
      subgroups using median and quartile cutoffs. Associations between biomarker
      expression and efficacy were analyzed. All statistical tests were two-sided.
      Results: The biomarker-evaluable population (n = 980) comprising 78.5% of the
      intent-to-treat population had representative baseline characteristics and
      efficacy outcomes. Neither prognostic nor predictive associations were seen for
      vascular endothelial growth factor (VEGF) receptor-2, neuropilin-1, or MET.
      Higher microvessel density (MVD; measured by CD31) showed predictive value for
      PFS (hazard ratio [HR] for bevacizumab vs placebo = 0.40, 95% confidence interval
      [CI] = 0.29 to 0.54, vs 0.80, 95% CI = 0.59 to 1.07, for high vs low MVD,
      respectively, P interaction = .003) and OS (HR = 0.67, 95% CI = 0.51 to 0.88, vs
      1.10, 95% CI = 0.84 to 1.44, P interaction = .02). Tumor VEGF-A was not
      predictive for PFS but showed potential predictive value for OS using a third
      quartile cutoff for high VEGF-A expression. Conclusions: These retrospective
      tumor biomarker analyses suggest a positive association between density of
      vascular endothelial cells (the predominant cell type expressing VEGF receptors)
      and tumor VEGF-A levels and magnitude of bevacizumab effect in ovarian cancer.
      The potential predictive value of MVD (CD31) and tumor VEGF-A is consistent with
      a mechanism of action driven by VEGF-A signaling blockade.

PMID- 29059428
TI  - Cost-effectiveness Analysis Comparing Conventional, Hypofractionated, and
      Intraoperative Radiotherapy for Early-Stage Breast Cancer.
AB  - Background: Early-stage breast cancer is among the most prevalent and costly
      malignancies treated in the American health care system. Adjuvant radiotherapy
      after lumpectomy represents a substantial portion of breast cancer expenditures.
      The relative value of novel radiotherapeutic approaches such as intraoperative
      radiotherapy (IORT) and hypofractionated whole breast irradiation (HF-WBI)
      compared with conventionally fractionated whole breast irradiation (CF-WBI) is
      unknown. Therefore, we used prospectively collected outcomes from randomized
      clinical trials (RCTs) to compare the cost-effectiveness of these approaches.
      Methods: We constructed a decision-analytic model that followed women who were
      treated with lumpectomy for early-stage breast cancer. Recurrence, mortality,
      complication rates, and utilities (five-year radiation-associated quality of life
      scores), were extracted from RCTs. Costs were based on Medicare reimbursement
      rates. Cost-effectiveness from societal and health care sector perspectives was
      estimated considering two scenarios-the first assumes that radiation-associated
      disutility persists five years after treatment, and the second assumes that
      disutility discontinues. Lifetime outcomes were summarized using incremental cost
      effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity
      analyses evaluated the robustness of the results. Results: HF-WBI dominated CF
      WBI (ie, resulted in higher quality-adjusted life-years [QALYs] and lower cost)
      in all scenarios. HF-WBI also had a greater likelihood of cost-effectiveness
      compared with IORT; under a societal perspective that assumes that radiation
      associated disutility persists, HF-WBI results in an ICER of $17 024 per QALY
      compared with IORT with a probability of cost-effectiveness of 80% at the $100
      000 per QALY willingness-to-pay threshold. If radiation-associated disutility is
      assumed to discontinue, the ICER is lower ($11 461/QALY), resulting in an even
      higher (83%) probability of relative cost-effectiveness. The ICER was most
      sensitive to the probability of metastasis and treatment cost. Conclusions: For
      women with early-stage breast cancer requiring adjuvant radiotherapy, HF-WBI is
      cost-effective compared with CF-WBI and IORT.

PMID- 29059429
TI  - The Dollars and Sense of Hypofractionated Breast Radiation.

PMID- 29059431
TI  - Genetic Determinants of Breast Cancer Risk in Childhood Cancer Survivors.

PMID- 29059432
TI  - A Phamacoeconomic Analysis of Personalized Dosing vs Fixed Dosing of
      Pembrolizumab in Firstline PD-L1-Positive Non-Small Cell Lung Cancer.
AB  - Background: In October 2016, pembrolizumab became the new standard of care for
      firstline treatment of patients with metastatic non-small cell lung cancer
      (mNSCLC) whose tumors express programmed death ligand 1 in at least 50% of cells.
      The US Food and Drug Administration-recommended dose is 200 mg every three weeks.
      Multiple studies have demonstrated equivalent efficacy with weight-based doses
      between 2 mg/kg and 10 mg/kg. The objective of this study was to compare the
      economic impact of using personalized dosing (2 mg/kg) vs fixed dosing (200 mg)
      in the firstline setting of mNSCLC. Methods: We performed a budget impact
      analysis from the US societal perspective to compare fixed dosing with
      personalized dosing. We calculated the target population and weight of patients
      who would be treated with pembrolizumab annually in the firstline setting. Using
      survival curves from the KEYNOTE 024 trial with Weibull extrapolation, we
      estimated the mean number of cycles that patients would receive. Using the
      Medicare average sales price, we calculated the difference in cost between
      personalized and fixed dosing. Results: Our base case model demonstrates that the
      total annual cost of pembrolizumab with fixed dosing is US $3 440 127 429, and
      with personalized dosing it is US $2 614 496 846. The use of personalized dosing
      would lead to a 24.0% annual savings of US $825 630 583 in the United States.
      Conclusions: Personalized dosing of pembrolizumab may have the potential to save
      approximately $0.825 billion annually in the United States, likely without
      impacting outcomes. This option should be considered for the firstline management
      of PD-L1-positive advanced lung cancer.

PMID- 29059434
TI  - Breaking Mitochondrial Fasting for Cancer Treatment: Old Wine in New Bottles.

PMID- 29059430
TI  - Genome-Wide Association Study to Identify Susceptibility Loci That Modify
      Radiation-Related Risk for Breast Cancer After Childhood Cancer.
AB  - Background: Childhood cancer survivors treated with chest-directed radiotherapy
      have substantially elevated risk for developing breast cancer. Although genetic
      susceptibility to breast cancer in the general population is well studied, large
      scale evaluation of breast cancer susceptibility after chest-directed
      radiotherapy for childhood cancer is lacking. Methods: We conducted a genome-wide
      association study of breast cancer in female survivors of childhood cancer,
      pooling two cohorts with detailed treatment data and systematic, long-term follow
      up: the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. The study
      population comprised 207 survivors who developed breast cancer and 2774 who had
      not developed any subsequent neoplasm as of last follow-up. Genotyping and
      subsequent imputation yielded 16 958 466 high-quality variants for analysis. We
      tested associations in the overall population and in subgroups stratified by
      receipt of lower than 10 and 10 or higher gray breast radiation exposure. We
      report P values and pooled per-allele risk estimates from Cox proportional
      hazards regression models. All statistical tests were two-sided. Results: Among
      survivors who received 10 or higher gray breast radiation exposure, a locus on
      1q41 was associated with subsequent breast cancer risk (rs4342822, nearest gene
      PROX1 , risk allele frequency in control subjects [RAF controls ] = 0.46, hazard
      ratio = 1.92, 95% confidence interval = 1.49 to 2.44, P = 7.09 * 10 -9 ). Two
      rare variants also showed potentially promising associations (breast radiation
      >=10 gray: rs74949440, 11q23, TAGLN , RAF controls = 0.02, P = 5.84 * 10 -8 ; <10
      gray: rs17020562, 1q32.3, RPS6KC1 , RAF controls = 0.0005, P = 6.68 * 10 -8 ).
      Associations were restricted to these dose subgroups, with consistent findings in
      the two survivor cohorts. Conclusions: Our study provides strong evidence that
      germline genetics outside high-risk syndromes could modify the effect of
      radiation exposure on breast cancer risk after childhood cancer.

PMID- 29059433
TI  - An ERBB1-3 Neutralizing Antibody Mixture With High Activity Against Drug
      Resistant HER2+ Breast Cancers With ERBB Ligand Overexpression.
AB  - Background: Plasticity of the ERBB receptor network has been suggested to cause
      acquired resistance to anti-human epidermal growth factor receptor 2 (HER2)
      therapies. Thus, we studied whether a novel approach using an ERBB1-3
      neutralizing antibody mixture can block these compensatory mechanisms of
      resistance. Methods: HER2+ cell lines and xenografts (n >= 6 mice per group) were
      treated with the ERBB1-3 antibody mixture Pan-HER, trastuzumab/lapatinib (TL),
      trastuzumab/pertuzumab (TP), or T-DM1. Downregulation of ERBB receptors was
      assessed by immunoblot analysis and immunohistochemistry. Paired pre- and post-T
      DM1 tumor biopsies from patients (n = 11) with HER2-amplified breast cancer were
      evaluated for HER2 and P-HER3 expression by immunohistochemistry and/or
      fluorescence in situ hybridization. ERBB ligands were measured by quantitative
      reverse transcription polymerase chain reaction. Drug-resistant cells were
      generated by chronic treatment with T-DM1. All statistical tests were two-sided.
      Results: Treatment with Pan-HER inhibited growth and promoted degradation of
      ERBB1-3 receptors in a panel of HER2+ breast cancer cells. Compared with TL, TP,
      and T-DM1, Pan-HER induced a similar antitumor effect against established BT474
      and HCC1954 tumors, but was superior to TL against MDA-361 xenografts (TL mean =
      2026 mm 3 , SD = 924 mm 3 , vs Pan-HER mean = 565 mm 3 , SD = 499 mm 3 , P =
      .04). Pan-HER-treated BT474 xenografts did not recur after treatment
      discontinuation, whereas tumors treated with TL, TP, and T-DM1 did. Post-TP and
      post-T-DM1 recurrent tumors expressed higher levels of neuregulin-1 (NRG1), HER3
      and P-HER3 (all P < .05). Higher levels of P-HER3 protein and NRG1 mRNA were also
      observed in HER2+ breast cancers progressing after T-DM1 and trastuzumab (NRG1
      transcript fold change +/- SD; pretreatment = 2, SD = 1.9, vs post-treatment =
      11.4, SD = 10.3, P = .04). The HER3-neutralizing antibody LJM716 resensitized the
      drug-resistant cells to T-DM1, suggesting a causal association between the NRG1
      HER3 axis and drug resistance. Finally, Pan-HER treatment inhibited growth of HR6
      trastuzumab- and T-DM1-resistant xenografts. Conclusions: These data suggest that
      upregulation of a NRG1-HER3 axis can mediate escape from anti-HER2 therapies.
      Further, multitargeted antibody mixtures, such as Pan-HER, can simultaneously
      remove and/or block targeted ERBB receptor and ligands, thus representing an
      effective approach against drug-sensitive and -resistant HER2+ cancers.

PMID- 29059435
TI  - Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate
      Dehydrogenase Kinase (PDC/PDK) Axis in Cancer.
AB  - The mitochondrial pyruvate dehydrogenase complex (PDC) irreversibly
      decarboxylates pyruvate to acetyl coenzyme A, thereby linking glycolysis to the
      tricarboxylic acid cycle and defining a critical step in cellular bioenergetics.
      Inhibition of PDC activity by pyruvate dehydrogenase kinase (PDK)-mediated
      phosphorylation has been associated with the pathobiology of many disorders of
      metabolic integration, including cancer. Consequently, the PDC/PDK axis has long
      been a therapeutic target. The most common underlying mechanism accounting for
      PDC inhibition in these conditions is post-transcriptional upregulation of one or
      more PDK isoforms, leading to phosphorylation of the E1alpha subunit of PDC. Such
      perturbations of the PDC/PDK axis induce a "glycolytic shift," whereby affected
      cells favor adenosine triphosphate production by glycolysis over mitochondrial
      oxidative phosphorylation and cellular proliferation over cellular quiescence.
      Dichloroacetate is the prototypic xenobiotic inhibitor of PDK, thereby
      maintaining PDC in its unphosphorylated, catalytically active form. However,
      recent interest in the therapeutic targeting of the PDC/PDK axis for the
      treatment of cancer has yielded a new generation of small molecule PDK
      inhibitors. Ongoing investigations of the central role of PDC in cellular energy
      metabolism and its regulation by pharmacological effectors of PDKs promise to
      open multiple exciting vistas into the biochemical understanding and treatment of
      cancer and other diseases.

PMID- 29059436
TI  - Raising the Dose and Raising the Cost: The Case of Pembrolizumab in Lung Cancer.

PMID- 29059437
TI  - Obstetrical Care in Survivors of Childhood Cancer: Utilization of Unique Linked
      Databases to Further Refine Consensus Guidelines.

PMID- 29059439
TI  - Real-world Data for Clinical Evidence Generation in Oncology.
AB  - Conventional cancer clinical trials can be slow and costly, often produce results
      with limited external validity, and are difficult for patients to participate in.
      Recent technological advances and a dynamic policy landscape in the United States
      have created a fertile ground for the use of real-world data (RWD) to improve
      current methods of clinical evidence generation. Sources of RWD include
      electronic health records, insurance claims, patient registries, and digital
      health solutions outside of conventional clinical trials. A definition focused on
      the original intent of data collected at the point of care can distinguish RWD
      from conventional clinical trial data. When the intent of data collection at the
      point of care is research, RWD can be generated using experimental designs
      similar to those employed in conventional clinical trials, but with several
      advantages that include gains in efficient execution of studies with an
      appropriate balance between internal and external validity. RWD can support
      active pharmacovigilance, insights into the natural history of disease, and the
      development of external control arms. Prospective collection of RWD can enable
      evidence generation based on pragmatic clinical trials (PCTs) that support
      randomized study designs and expand clinical research to the point of care. PCTs
      may help address the growing demands for access to experimental therapies while
      increasing patient participation in cancer clinical trials. Conducting valid real
      world studies requires data quality assurance through auditable data abstraction
      methods and new incentives to drive electronic capture of clinically relevant
      data at the point of care.

PMID- 29059440
TI  - US Medical Schools' Awareness of Their Students Who Smoke, Cessation Programs
      Available, and the Potential Impact on Residency Match.

PMID- 29059438
TI  - Loss of DNA Damage Response in Neuroblastoma and Utility of a PARP Inhibitor.
AB  - Background: Neuroblastoma (NB) is the most common solid tumor found in children,
      and deletions within the 11q region are observed in 11% to 48% of these tumors.
      Notably, such tumors are associated with poor prognosis; however, little is known
      regarding the molecular targets located in 11q. Methods: Genomic alterations of
      ATM , DNA damage response (DDR)-associated genes located in 11q ( MRE11A, H2AFX ,
      and CHEK1 ), and BRCA1, BARD1, CHEK2, MDM2 , and TP53 were investigated in 45 NB
      derived cell lines and 237 fresh tumor samples. PARP (poly [ADP-ribose]
      polymerase) inhibitor sensitivity of NB was investigated in in vitro and invivo
      xenograft models. All statistical tests were two-sided. Results: Among 237 fresh
      tumor samples, ATM, MRE11A, H2AFX , and/or CHEK1 loss or imbalance in 11q was
      detected in 20.7% of NBs, 89.8% of which were stage III or IV. An additional 7.2%
      contained ATM rare single nucleotide variants (SNVs). Rare SNVs in DDR-associated
      genes other than ATM were detected in 26.4% and were mutually exclusive. Overall,
      samples with SNVs and/or copy number alterations in these genes accounted for
      48.4%. ATM-defective cells are known to exhibit dysfunctions in homologous
      recombination repair, suggesting a potential for synthetic lethality by PARP
      inhibition. Indeed, 83.3% NB-derived cell lines exhibited sensitivity to PARP
      inhibition. In addition, NB growth was markedly attenuated in the xenograft group
      receiving PARP inhibitors (sham-treated vs olaprib-treated group; mean [SD] tumor
      volume of sham-treated vs olaprib-treated groups = 7377 [1451] m 3 vs 298 [312] m
      3 , P = .001, n = 4). Conclusions: Genomic alterations of DDR-associated genes
      including ATM, which regulates homologous recombination repair, were observed in
      almost half of NBs, suggesting that synthetic lethality could be induced by
      treatment with a PARP inhibitor. Indeed, DDR-defective NB cell lines were
      sensitive to PARP inhibitors. Thus, PARP inhibitors represent candidate NB
      therapeutics.

PMID- 29059441
TI  - A Survey of Nicotine Yields in Small Cigar Smoke: Influence of Cigar Design and
      Smoking Regimens.
AB  - Introduction: Although the popularity of small cigar brands that resemble
      cigarettes, including both little cigars (LC) and filtered cigars (FC), has been
      on the rise, little is known about the delivery of nicotine from these products.
      Our objective was to determine the nicotine yields of small cigars in comparison
      to cigarettes. Methods: Nicotine yields from LC, FC, and 3R4F and 1R6F research
      cigarettes were determined from mainstream smoke generated on a smoking machine
      under the International Organization of Standardization (ISO) and Canadian
      Intense (CI) methods. Market characteristics (price and package label) and
      physical features (filter ventilation, product weight and filter weight, product
      length, and diameter) were also determined for eight brands of small cigars.
      Results: Nicotine yields in small cigars averaged 1.24 and 3.49 mg/unit on ISO
      and CI regimens, respectively, compared with 0.73 and 2.35 mg/unit, respectively,
      for the research cigarettes. Nicotine yields per puff were similar between small
      cigars and cigarettes. We also found that FC did not differ from LC in nicotine
      yields. FC and LC differ from each other in many physical design features (unit
      weight, filter weight, and filter length), but are similar in others (unit
      length, diameter, and filter ventilation). Conclusions: Nicotine delivery from
      small cigars is similar to or greater than that from cigarettes. Thus, for future
      research and regulatory purposes, standard definitions need to be developed for
      small cigars, and FC and LC should be evaluated as separate entities.
      Implications: Small cigars are similar to cigarettes in their design and use.
      Although nicotine yields per puff were similar between products, small cigars
      delivered substantially higher amounts of nicotine per unit than cigarettes.
      These findings support the growing body of evidence to justify regulating all
      small cigars, including LC and FC in a similar fashion as cigarettes.

PMID- 29059442
TI  - Financial Incentives for Smoking Abstinence in Homeless Smokers: A Pilot
      Randomized Controlled Trial.
AB  - Introduction: Three-quarters of homeless people smoke cigarettes. Financial
      incentives for smoking abstinence have appeared promising in nonexperimental
      studies of homeless smokers, but randomized controlled trial (RCT) data are
      lacking. Methods: We conducted a pilot RCT of financial incentives for homeless
      smokers. Incentive arm participants (N = 25) could earn escalating $15-$35
      rewards for brief smoking abstinence (exhaled carbon monoxide <8 parts per
      million) assessed 14 times over 8 weeks. Control arm participants (N = 25) were
      given $10 at each assessment regardless of abstinence. All participants were
      offered nicotine patches and counseling. The primary outcome was a repeated
      measure of brief smoking abstinence across 14 assessments. The secondary outcome
      was brief abstinence at 8 weeks. Exploratory outcomes were self-reported 1-day
      and 7-day abstinence from (1) any cigarette and (2) any puff of a cigarette.
      Other outcomes included 24-hour quit attempts, nicotine patch use, counseling
      attendance, and changes in alcohol and drug use. Results: Compared to control,
      incentive arm participants were more likely to achieve brief abstinence overall
      (odds ratio 7.28, 95% confidence interval 2.89 to 18.3) and at 8 weeks (48% vs.
      8%, p = .004). Similar effects were seen for 1-day abstinence, but 7-day puff
      abstinence was negligible in both arms. Incentive arm participants made more quit
      attempts (p = .03). Nicotine patch use and counseling attendance were not
      significantly different between the groups. Alcohol and drug use did not change
      significantly in either group. Conclusions: Among homeless smokers, financial
      incentives increased brief smoking abstinence and quit attempts without worsening
      substance use. This approach merits further development focused on promoting
      sustained abstinence. Registration: ClinicalTrials.gov (NCT02565381).
      Implications: Smoking is common among homeless people, and conventional tobacco
      treatment strategies have yielded modest results in this population. This pilot
      RCT suggests that financial incentives may be a safe way to promote brief smoking
      abstinence and quit attempts in this vulnerable group of smokers. However,
      further development is necessary to translate this approach into real-world
      settings and to promote sustained periods of smoking abstinence.

PMID- 29059443
TI  - Availability and Placement of Electronic Nicotine Delivery Systems at the Point
      of-Sale.
AB  - Introduction: Electronic nicotine delivery systems (ENDS) are widely available
      and come in a variety of forms, including disposable cigalikes and refillable
      tank systems. However, little is known about their placement at the point-of
      sale. We explored the placement of various ENDS types among tobacco retailers.
      Methods: Systematic assessments at the point-of-sale were completed by trained
      data collectors in 90 tobacco retailers, including grocery stores, convenience
      stores, and pharmacies in North Carolina, United States. Availability and
      placement of various ENDS types including cigalikes, e-hookahs, tank systems, and
      e-liquids was recorded. Results: Almost all retailers (97.8%) sold cigalikes;
      41.4% sold devices labeled as e-hookahs; 54.4% sold tank systems; and 56.2% sold
      e-liquids. Fewer than half of stores placed ENDS exclusively behind the counter;
      significant differences in ENDS placement were found by store type. Grocery
      stores carried cigalikes, tank systems, and e-liquids and placed them exclusively
      behind the counter. Pharmacies only sold cigalikes; most placed them exclusively
      behind the counter (91.7%) with cessation aids and other tobacco products.
      Convenience stores carried all ENDS types and placed them with other tobacco
      products (55.1%) and candy (17.4%). Only about one-third of convenience stores
      placed ENDS exclusively behind the counter. Conclusions: This exploratory study
      shows ENDS availability and placement at the point-of-sale varies by retailer
      type. Pharmacies placed cigalikes with cessation aids behind the counter
      suggesting their ability to aid in smoking cessation. Most convenience stores
      placed ENDS in self-service locations, making them easily accessible to youth.
      Findings highlight the need for ENDS regulation at the point-of-sale.
      Implications: Our study highlights the need for regulatory efforts aimed at ENDS
      placement at the point-of-sale. While pharmacies and grocery stores offered fewer
      ENDS types and typically placed them in clerk-assisted locations, all ENDS types
      were found at convenience stores, some of which were placed in youth-friendly
      locations. Regulatory efforts to control ENDS placement and limit youth exposure
      should be examined, such as requiring products be placed in clerk-assisted
      locations and banning ENDS placement next to candy.

PMID- 29059444
TI  - Increases in Cigarette Consumption and Decreases in Smoking Intensity When
      Nondaily Smokers Are Provided With Free Cigarettes.
AB  - Introduction: Studies testing novel tobacco products often provide participants
      with free product and assess consumption. Some, but not all, studies find that
      providing free cigarettes increases smoking. We tested changes in smoking when
      free cigarettes were provided to nondaily, intermittent smokers, who constitute
      one-third of US adult smokers. Methods: Cigarette consumption was assessed by
      Time-Line Follow-Back in 235 intermittent smokers for two 2-week periods: when
      providing their own cigarettes and when provided own-brand cigarettes for free.
      Smoking topography and carbon monoxide boost were assessed for one cigarette at
      the end of each period. Results: Cigarette consumption increased significantly,
      by 66% (from 1.98 to 3.28 cigarettes per day), when cigarettes were available for
      free; both the number of days the subjects smoked and the number of cigarettes on
      those days increased. The increases were significantly greater among African
      Americans, those Fagerstrom Tobacco Nicotine Dependence scores >0, those with
      incomes less than US $25,000 per year, those who engaged in greater conscious
      restraint of smoking, and for smokers of menthol cigarettes, or "longs." Smoking
      intensity (smoke volume, by topography) and carbon monoxide boost decreased
      significantly when cigarettes were provided for free. Conclusions: Providing
      intermittent smokers with free cigarettes substantially increased their smoking
      while decreasing smoking intensity. The increases in smoking varied according to
      multiple individual and cigarette-type differences. These phenomena may
      complicate interpretation of studies that compare consumption of a free test
      product with cigarette consumption or constituent exposure when smokers are
      providing their own cigarettes. They also suggest that cigarette cost and
      variations in low-level dependence and in smoking restraint are factors in
      nondaily smoking. Implications: The study shows that providing nondaily smokers
      with free cigarettes increases cigarette consumption, but does differentially for
      different subgroups and cigarette types, while also decreasing smoking intensity.
      This suggests the value of using free-cigarette baseline data in studies where
      interventions provide free cigarettes.

PMID- 29059445
TI  - Elevated CO2 Induces Root Defensive Mechanisms in Tomato Plants When Dealing with
      Ammonium Toxicity.
AB  - An adequate carbon supply is fundamental for plants to thrive under ammonium
      stress. In this work, we studied the mechanisms involved in tomato (Solanum
      lycopersicum L.) response to ammonium toxicity when grown under ambient or
      elevated CO2 conditions (400 or 800 p.p.m. CO2). Tomato roots were observed to be
      the primary organ dealing with ammonium nutrition. We therefore analyzed nitrogen
      (N) and carbon (C) metabolism in the roots, integrating the physiological
      response with transcriptomic regulation. Elevated levels of CO2 preferentially
      stimulated root growth despite the high ammonium content. The induction of
      anaplerotic enzymes from the tricarboxylic acid (TCA) cycle led to enhanced amino
      acid synthesis under ammonium nutrition. Furthermore, the root transcriptional
      response to ammonium toxicity was improved by CO2-enriched conditions, leading to
      higher expression of stress-related genes, as well as enhanced modulation of
      genes related to signaling, transcription, transport and hormone metabolism.
      Tomato roots exposed to ammonium stress also showed a defense-like
      transcriptional response according to the modulation of genes related to
      detoxification and secondary metabolism, involving principally terpenoid and
      phenolic compounds. These results indicate that increasing C supply allowed the
      co-ordinated regulation of root defense mechanisms when dealing with ammonium
      toxicity.

PMID- 29059446
TI  - Action Spectrum of Photoinhibition in the Diatom Phaeodactylum tricornutum.
AB  - Light-dependent electron transfer is necessary for photosynthesis, but light also
      damages PSII. Light-induced damage to PSII is called photoinhibition, and the
      damaging reactions of photoinhibition are still under debate. Diatoms possess an
      exotic combination of light-harvesting pigments, Chls a/c and fucoxanthin, making
      them an interesting platform for studying the photoreceptors of photoinhibition.
      We first confirmed the direct proportionality of photoinhibition to the photon
      flux density of incident light in the diatom Phaeodactylum tricornutum.
      Phaeodactylum is known for its efficient non-photochemical quenching, and the
      effect of this photoprotective mechanism on photoinhibition was tested.
      Photoinhibition proceeded essentially at the same rate in blue-light-grown
      Phaeodactylum cells that are capable of non-photochemical quenching and in red
      light-grown, non-photochemical quenching-deficient cells. To obtain more insight
      into how the pigment composition of diatoms affects photoinhibition, we measured
      the action spectrum of photoinhibition in Phaeodactylum. In visible light, the
      action spectrum resembled the absorption spectrum of Phaeodactylum, and UV
      radiation caused much more photoinhibition than visible light. Comparison of the
      action spectrum of photoinhibition with the absorption spectrum and the
      excitation spectrum of 77 K PSII fluorescence emission confirmed that
      photosynthetic pigments are involved in photoinhibition, but the photoinhibitory
      efficiency of red light is weak, suggesting that the role of light-harvesting
      pigments as light receptors of photoinhibition is secondary. Finally, we compared
      photoinhibition in Phaeodactylum with that in other photosynthetic organisms, and
      our data indicate that the PSII reaction centers of Phaeodactylum are not
      particularly well protected against the primary damage of photoinhibition.

PMID- 29059447
TI  - EGFRvIII vaccine in glioblastoma-InACT-IVe or not ReACTive enough?

PMID- 29059448
TI  - Meeting Update-World Federation of Neuro-Oncology Societies (WFNOS) Meeting 2017.

PMID- 29059449
TI  - Smoking and Tobacco-Free Policies in Women's Residential Substance Use Disorder
      Treatment Facilities: A Community-Engaged Approach.
AB  - Introduction: The purpose of this study was to (1) describe the role of smoking
      in the lives of women in residential substance use disorder (SUD) treatment and
      (2) explore perceptions of the facilitators and barriers to tobacco-free policy
      among women in residential SUD treatment. Methods: This was a community-engaged
      study using qualitative descriptive methods. We first recruited women in a
      residential SUD treatment facility to participate on a community research team.
      Interviews with staff (N = 10) and focus groups with clients (N = 42) were
      conducted using guides informed by the community research team. Interviews and
      focus groups were analyzed using content analysis. Results: There were two themes
      related to the role of smoking in the women's lives: (1) smoking facilitates
      socialization and (2) smoking as a coping mechanism. There were three themes
      related to the benefits of tobacco-free policy: (1) improved health, (2) support
      for continued abstinence from a previous tobacco-free placement (eg, prison), and
      (3) less grounds up-keep. Barriers to tobacco-free policy included (1) lack of an
      alternative coping mechanism to smoking, (2) fear that a tobacco-free policy
      would drive clients away, and (3) anticipation of implementation challenges.
      Conclusions: Many women in residential SUD treatment smoke, which they attribute
      to the fact that smoking is used to facilitate socialization and cope with
      stress. Future research is needed to develop and test messages to counter the
      misperception that smoking is an effective method to cope with stress.
      Ultimately, evidence-based tobacco-free policies are needed to reduce tobacco
      related disease among women with SUDs. Implications: To promote smoking cessation
      among women with substance use disorders through evidence-based tobacco policy,
      it is necessary to first understand the role of smoking in their lives as well as
      facilitators and barriers to tobacco-free policy in residential treatment
      facilities. Participants reported that smoking facilitated socialization and
      served as a coping mechanism. Tobacco-free policies have many benefits, including
      improved health, support for continued abstinence from a previous tobacco-free
      placement (eg, prison), and less grounds up-keep. Barriers include the lack of an
      alternative coping mechanism, fear that a tobacco-free policy would drive away
      clients and anticipation of implementation challenges. To reduce the burden of
      tobacco-related morbidity and mortality among women and their children, it is
      necessary to catalyze a culture change in behavioral health settings to
      prioritize the treatment of tobacco alongside treatment of other addictions.

PMID- 29059450
TI  - Prenatal Nicotine Exposure Disrupts Infant Neural Markers of Orienting.
AB  - Introduction: Prenatal nicotine exposure (PNE) from maternal cigarette smoking is
      linked to developmental deficits, including impaired auditory processing,
      language, generalized intelligence, attention, and sleep. Fetal brain undergoes
      massive growth, organization, and connectivity during gestation, making it
      particularly vulnerable to neurotoxic insult. Nicotine binds to nicotinic
      acetylcholine receptors, which are extensively involved in growth, connectivity,
      and function of developing neural circuitry and neurotransmitter systems. Thus,
      PNE may have long-term impact on neurobehavioral development. The purpose of this
      study was to compare the auditory K-complex, an event-related potential
      reflective of auditory gating, sleep preservation and memory consolidation during
      sleep, in infants with and without PNE and to relate these neural correlates to
      neurobehavioral development. Methods: We compared brain responses to an auditory
      paired-click paradigm in 3- to 5-month-old infants during Stage 2 sleep, when the
      K-complex is best observed. We measured component amplitude and delta activity
      during the K-complex. Results: Infants with PNE demonstrated significantly
      smaller amplitude of the N550 component and reduced delta-band power within
      elicited K-complexes compared to nonexposed infants and also were less likely to
      orient with a head turn to a novel auditory stimulus (bell ring) when awake.
      Conclusions: PNE may impair auditory sensory gating, which may contribute to
      disrupted sleep and to reduced auditory discrimination and learning, attention re
      orienting, and/or arousal during wakefulness reported in other studies.
      Implications: Links between PNE and reduced K-complex amplitude and delta power
      may represent altered cholinergic and GABAergic synaptic programming and possibly
      reflect early neural bases for PNE-linked disruptions in sleep quality and
      auditory processing. These may pose significant disadvantage for language
      acquisition, attention, and social interaction necessary for academic and social
      success.

PMID- 29059451
TI  - Nicotine Increases Activation to Anticipatory Valence Cues in Anterior Insula and
      Striatum.
AB  - Introduction: Smoking is associated with significant morbidity and mortality.
      Understanding the neurobiology of the rewarding effects of nicotine promises to
      aid treatment development for nicotine dependence. Through its actions on
      mesolimbic dopaminergic systems, nicotine engenders enhanced responses to drug
      related cues signaling rewards, a mechanism hypothesized to underlie the
      development and maintenance of nicotine addiction. Methods: We evaluated the
      effects of acute nicotine on neural responses to anticipatory cues signaling
      (nondrug) monetary reward or loss among 11 nonsmokers who had no prior history of
      tobacco smoking. In a double-blind, crossover design, participants completed
      study procedures while wearing nicotine or placebo patches at least 1 week apart.
      In each drug condition, participants underwent functional magnetic resonance
      imaging while performing the monetary incentive delay task and performed a
      probabilistic monetary reward task, probing reward responsiveness as measured by
      response bias toward a more frequently rewarded stimulus. Results: Nicotine
      administration was associated with enhanced activation, compared with placebo, of
      right fronto-anterior insular cortex and striatal regions in response to cues
      predicting possible rewards or losses and to dorsal anterior cingulate for
      rewards. Response bias toward rewarded stimuli correlated positively with insular
      activation to anticipatory cues. Conclusion: Nicotinic enhancement of monetary
      reward-related brain activation in the insula and striatum in nonsmokers
      dissociated acute effects of nicotine from effects on reward processing due to
      chronic smoking. Reward responsiveness predicted a greater nicotinic effect on
      insular activation to salient stimuli. Implications: Previous research
      demonstrates that nicotine enhances anticipatory responses to rewards in regions
      targeted by midbrain dopaminergic systems. The current study provides evidence
      that nicotine also enhances responses to rewards and losses in the anterior
      insula. A previous study found enhanced insular activation to rewards and losses
      in smokers and ex-smokers, a finding that could be due to nicotine sensitization
      or factors related to current or past smoking. Our finding of enhanced anterior
      insula response after acute administration of nicotine in nonsmokers provides
      support for nicotine-induced sensitization of insular response to rewards and
      losses.

PMID- 29059452
TI  - First-Trimester Crown-Rump Length and Risk of Chromosomal Aberrations-A
      Systematic Review and Meta-analysis.
AB  - Importance: Lower than expected first-trimester crown-rump length (CRL) is a
      common sonographic finding, usually leading to reassessment of gestational age.
      Objective: The aim of this study was to perform a meta-analysis defining the risk
      of chromosomal aberrations in pregnancies with decreased first-trimester CRL.
      Evidence Acquisition: A search was conducted by a research librarian in 5
      databases, with no time or language restrictions. Original researches examining
      the risk of chromosomal aberrations in pregnancies with low CRL were selected.
      The effect estimates were presented as odds ratios with 95% confidence
      intervals). Results: Following screening of 3894 references, 12 articles were
      selected. Only 2 articles directly fulfilled the review goals, comparing the
      rates of chromosomal aberrations in small-CRL versus normal-CRL fetuses. Combined
      analysis of these 2 studies, encompassing a total of 403 fetuses with small CRL
      and 4047 control pregnancies, yielded an odds ratio of 5.54 (95% confidence
      interval, 1.2-26.1) for abnormal karyotype in small-CRL fetuses. Ten studies
      compared CRL in fetuses with specific chromosomal aberrations to pregnancies with
      normal karyotype, yielding a significant growth delay in fetuses with trisomy 18
      (6 of 7 articles) and triploidy, but not in fetuses with trisomy 21. Overall
      quality of evidence was rated as "very low" using Grading of Recommendations
      Assessment, Development and Evaluation criteria. Conclusions and Relevance: Our
      review results indicate that low first-trimester CRL might be associated with a
      significantly increased risk of chromosomal anomalies. Thus, invasive prenatal
      testing or cell-free DNA screening might be offered in such pregnancies,
      particularly if dating is certain.

PMID- 29059453
TI  - What's New in Prenatal Genetics? A Review of Current Recommendations and
      Guidelines.
AB  - Importance: The rapid development of prenatal genetic testing and screening tools
      and choices constantly challenges clinicians to stay up to date on current best
      practice. Objective: We sought to review, compare, and summarize recent national
      society guidelines on prepregnancy genetic screening and prenatal diagnosis for
      aneuploidy with a focus on changes and additions to previous guidelines. Evidence
      Acquisition: We performed a descriptive review of 8 recently published (2016
      2017) national guidelines and updates on prenatal genetic screening and testing
      including American Congress of Obstetricians and Gynecologists committee opinions
      and practice bulletins, Society for Maternal-Fetal Medicine consult series
      publications, and an American College of Medical Genetics and Genomics position
      statement. Topics included carrier screening, cell-free DNA screening,
      chromosomal microarray analysis, next-generation sequencing, and prenatal
      diagnostic testing. The recommendations in these publications were compared, and
      the additions and changes to previous recommendations and guidelines were
      summarized. Results: Recent publications contain many updates and changes to
      previous screening and testing strategies, most of which are consistent between
      professional societies. Although many new technologies have been integrated into
      prenatal diagnosis, some newer technologies are not yet routinely recommended for
      widespread use, often because of lack of clinical trials and validation studies.
      Conclusions: Prenatal screening and testing options are rapidly expanding. To
      provide best-practice prenatal care, obstetric care providers should educate
      themselves about the most up-to-date recommendations and be prepared to interpret
      and apply these guidelines to their patients. Society guidelines are largely in
      agreement.

PMID- 29059454
TI  - New Evidence to Guide Ectopic Pregnancy Diagnosis and Management.
AB  - Importance: Ectopic pregnancy is a leading source of morbidity and mortality in
      pregnancy, accounting for 1% to 2% of all pregnancies. Timely diagnosis and
      management of these abnormal gestations are vital to patient safety. Objective:
      The objective of this study was to describe recent evidence in the risk factors,
      diagnosis, and management of ectopic pregnancy. Evidence Acquisition:
      Comprehensive review of the published literature. Results: Recent literature
      describes newly identified risk factors for ectopic pregnancy, particularly those
      specific to assisted reproduction. Furthermore, evidence mounts for the utility
      of endometrial sampling for the diagnosis of pregnancy location, allowing a
      significant proportion of women to avoid methotrexate by diagnosing failing
      intrauterine pregnancies instead. Finally, recent, high-level evidence supports
      (in women with normal contralateral fallopian tubes) the equivalence of
      salpingectomy and salpingostomy regarding rates of subsequent intrauterine
      pregnancy and recurrent ectopic pregnancy. Conclusions and Relevance: While
      serial serum human chorionic gonadotropin levels and transvaginal ultrasound are
      the mainstays of ectopic pregnancy diagnosis, recent publications revisit the
      utility of endometrial sampling in diagnosing pregnancy location, using manual
      vacuum aspiration instead of the criterion-standard dilation and curettage.
      Expectant management of ectopic pregnancies is the subject of ongoing research,
      and in the meantime, treatment remains medical or surgical (dependent on clinical
      parameters and patient preference); salpingostomy and salpingectomy provide
      equivalent subsequent pregnancy outcomes in women with contralateral fallopian
      tubes in place.

PMID- 29059455
TI  - Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice.
AB  - : Postnatal liver development is characterized by hepatocyte growth,
      proliferation, and functional maturation. Notably, canonical Wnt signaling in
      hepatocytes has been identified as an important regulator of final adult liver
      size and metabolic liver zonation. The cellular origin of Wnt ligands responsible
      for homeostatic liver/body weight ratio (LW/BW) remained unclear, which was also
      attributable to a lack of suitable endothelial Cre driver mice. To
      comprehensively analyze the effects of hepatic angiocrine Wnt signaling on liver
      development and metabolic functions, we used endothelial subtype-specific Stab2
      Cre driver mice to delete Wls from hepatic endothelial cells (HECs). The
      resultant Stab2-Cretg/wt ;Wlsfl/fl (Wls-HECKO) mice were viable, but showed a
      significantly reduced LW/BW. Specifically, ablation of angiocrine Wnt signaling
      impaired metabolic zonation in the liver, as shown by loss of pericentral, beta
      catenin-dependent target genes such as glutamine synthase (Glul), RhBg, Axin2,
      and cytochrome P450 2E1, as well as by extended expression of periportal genes
      such as arginase 1. Furthermore, endothelial subtype-specific expression of a c
      terminally YFP-tagged Wls fusion protein in Wls-HECKO mice (Stab2-Cretg/wt
      ;Wlsfl/fl ;Rosa26:Wls-YFPfl/wt [Wls-rescue]) restored metabolic liver zonation.
      Interestingly, lipid metabolism was altered in Wls-HECKO mice exhibiting
      significantly reduced plasma cholesterol levels, while maintaining normal plasma
      triglyceride and blood glucose concentrations. On the contrary, zonal expression
      of Endomucin, LYVE1, and other markers of HEC heterogeneity were not altered in
      Wls-HECKO livers. CONCLUSION: Angiocrine Wnt signaling controls liver growth as
      well as development of metabolic liver zonation in mice, whereas intrahepatic HEC
      zonation is not affected. (Hepatology 2017).

PMID- 29059456
TI  - Case definitions for inclusion and analysis of endpoints in clinical trials for
      nonalcoholic steatohepatitis through the lens of regulatory science.
AB  - Nonalcoholic steatohepatitis (NASH) is an important cause of liver-related
      morbidity and mortality. There are no approved therapies, and the results of
      clinical trials have been difficult to compare due to inconsistent definitions of
      relevant disease parameters in patients with NASH. The natural course of the
      disease has not been rigorously characterized, particularly with respect to the
      contributions of underlying obesity, type 2 diabetes, and other comorbidities and
      the treatments provided for these comorbidities. Efforts to perform analyses of
      pooled data are limited by heterogeneous case definitions used across studies to
      define disease states. There remains a major unmet need in the field to develop
      standardized definitions for populations for interventional trials. Such
      definitions are expected to impact how endpoints for clinical trials are
      constructed. The Liver Forum is a multistakeholder effort including US and
      European regulatory agencies, academic investigators, professional and patient
      representative organizations, and industry to catalyze therapeutic development
      for NASH by developing potential solutions to barriers to development. The Case
      Definitions Working Group was established by The Liver Forum to evaluate the
      validity of case definitions for populations to be included in clinical trials
      for NASH from a regulatory science perspective. Based on such analyses, specific
      recommendations are provided noting the strengths and weaknesses of the case
      definitions along with knowledge gaps that require additional study. (Hepatology
      2018;67:2001-2012).

PMID- 29059458
TI  - Regorafenib for treatment of hepatocellular carcinoma.

PMID- 29059457
TI  - Systemic regulation of bilirubin homeostasis: Potential benefits of
      hyperbilirubinemia.
AB  - Neurotoxic bilirubin is the end product of heme catabolism in mammals. Bilirubin
      is solely conjugated by uridine diphospho-glucuronosyltransferase 1A1, which is a
      membrane-bound enzyme that catalyzes the transfer of glucuronic acid. Due to low
      function of hepatic and intestinal uridine diphospho-glucuronosyltransferase 1A1
      during the neonatal period, human neonates develop mild to severe physiological
      hyperbilirubinemia. Accumulation of bilirubin in the brain leads to the onset of
      irreversible brain damage, termed kernicterus. Breastfeeding is one of the most
      significant factors that increase the risk of developing kernicterus in infants.
      Why does this most natural way of feeding increase the risk of brain damage or
      even death? This question leads to the hypothesis that breast milk-induced
      hyperbilirubinemia might bring certain benefits that outweigh those risks. While
      bilirubin is neurotoxic and cytotoxic, this compound is also a potent
      antioxidant. There are studies showing improved clinical conditions in patients
      with hyperbilirubinemia. Accumulating evidence also shows that genetic
      polymorphisms linked to hyperbilirubinemia are beneficial against various
      diseases. In this review article, we first introduce the production, metabolism,
      and transport of bilirubin. We then discuss the potential benefits of neonatal
      and adult hyperbilirubinemia. Finally, epigenetic factors as well as metabolomic
      information associated with hyperbilirubinemia are described. This review article
      advances the understanding of the physiological importance of the paradoxical
      compound bilirubin. (Hepatology 2018;67:1609-1619).

PMID- 29059459
TI  - Molecular cloning and tissue distribution of a novel marmoset ABC transporter.
AB  - Common marmosets (Callithrix jacchus) have been recognized as a useful small non
      human primate model in preclinical testing for drug development. In this study, a
      cDNA of novel ATP-dependent efflux transporter ABCB1 was cloned from marmoset
      liver tissue. Marmoset ABCB1 cDNA encodes a protein of 1279 amino acid residues
      (MW = 141.4 kDa) containing characteristic regions of an ATP-binding cassette
      (ABC) protein, two hydrophobic transmembrane regions and two cytoplasmic
      nucleotide-binding regions, similar to human ABCB1. The deduced amino acid
      sequences were more highly identical (95%) to those of human ABCB1 compared with
      non-primate species such as dogs, pigs and rodents (79-90%). A close evolutionary
      relationship of ABCB1 among marmosets, cynomolgus and rhesus monkeys and humans
      was evident from a phylogenetic analysis using ABCB1 amino acid sequences from
      primates, dogs, pigs and rodents. Tissue distribution analyses by quantitative
      reverse transcription-polymerase chain reaction indicated that marmoset ABCB1
      mRNA was most abundant in kidneys, followed by small intestines and livers,
      similar to human ABCB1, and marmoset ABCB1 proteins in these tissues were also
      detected by immunoblotting. These results indicated that the primary structure
      and tissue distribution of ABCB1 in marmosets were similar to those of humans,
      suggesting similar molecular characteristics of ABCB1 between marmosets and
      humans.

PMID- 29059460
TI  - New presentation of autoimmune hepatitis with erythema multiforme.

PMID- 29059462
TI  - Benefit-risk assessment for sofosbuvir/velpatasvir/voxilaprevir based on patient
      population and hepatitis C virus genotype: U. S. Food and Drug Administration's
      evaluation.
AB  - : On July 18, 2017, the U.S. Food and Drug Administration (FDA) approved
      sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (Vosevi) fixed-dose combination
      (FDC), an interferon-free, complete regimen for adult patients with chronic
      hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis
      (Child-Pugh A) who have: * genotype 1, 2, 3, 4, 5, or 6 infection and have
      previously been treated with an HCV regimen containing a nonstructural protein 5A
      (NS5A) inhibitor; and * genotype 1a or 3 infection and have previously been
      treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor.
      Approval was based on an acceptable safety profile and high sustained virological
      response rates 12 weeks after the end of treatment (SVR12) in two phase 3
      clinical trials in subjects previously treated with a direct-acting antiviral
      (DAA) regimen. In POLARIS-1, 96% of SOF/VEL/VOX-treated subjects achieved SVR12.
      In POLARIS-4, 98% of SOF/VEL/VOX-treated subjects achieved SVR12. A key and
      challenging question in evaluating the data was determining the contribution of
      VOX to SOF/VEL and how this differed depending on the genotype and patient
      population. In this article, we provide our perspective on the issues considered
      in making these determinations, especially regarding the POLARIS-4 data in
      subjects who have previously been treated with a chronic HCV regimen containing
      sofosbuvir without an NS5A inhibitor. CONCLUSION: We seek to provide context as
      to why a broad indication was given for NS5A inhibitor-experienced patients (HCV
      genotypes 1-6) while the indication for NS5A inhibitor- naive patients was
      limited to HCV genotypes 1a and 3 only. (Hepatology 2017).

PMID- 29059463
TI  - Partial splenic artery embolization for severe hepatic myelopathy in cirrhosis.
AB  - Hepatic myelopathy (HM) is a devastating but rare complication of cirrhosis and
      portal hypertension that profoundly affects quality of life and improves only
      with liver transplantation. We present a case where progressive severe spastic
      paraparesis due to HM was substantially reversed with partial splenic artery
      emobilization (PSAE). (Hepatology 2018;67:1169-1171).

PMID- 29059461
TI  - Should we treat acute hepatitis C? A decision and cost-effectiveness analysis.
AB  - : It is not standard practice to treat patients with acute hepatitis C virus
      (HCV) infection. However, as the incidence of HCV in the United States continues
      to rise, it may be time to re-evaluate acute HCV management in the era of direct
      acting antiviral (DAA) agents. In this study, a microsimulation model was
      developed to analyze the trade-offs between initiating HCV therapy in the acute
      versus chronic phase of infection. By simulating the lifetime clinical course of
      patients with acute HCV infection, we were able to project long-term outcomes
      such as quality-adjusted life years (QALYs) and costs. We found that treating
      acute HCV versus deferring treatment until the chronic phase increased QALYs by
      0.02 and increased costs by $483 in patients not at risk of transmitting HCV. The
      resulting incremental cost-effectiveness ratio was $19,991 per QALY,
      demonstrating that treatment of acute HCV was cost-effective using a willingness
      to-pay threshold of $100,000 per QALY. In patients at risk of transmitting HCV,
      treating acute HCV became cost-saving, increasing QALYs by 0.03 and decreasing
      costs by $3,655. CONCLUSION: Immediate treatment of acute HCV with DAAs can
      improve clinical outcomes and be highly cost-effective or cost-saving compared
      with deferring treatment until the chronic phase of infection. If future studies
      continue to demonstrate effective HCV cure with shorter 6-week treatment
      duration, then it may be time to revisit current HCV guidelines to incorporate
      recommendations that account for the clinical and economic benefits of treating
      acute HCV in the era of DAAs. (Hepatology 2018;67:837-846).

PMID- 29059464
TI  - Fluoride supplementation (with tablets, drops, lozenges or chewing gum) in
      pregnant women for preventing dental caries in the primary teeth of their
      children.
AB  - BACKGROUND: Dental caries (tooth decay) is one of the most common chronic
      childhood diseases. Caries prevalence in most industrialised countries has
      declined among children over the past few decades. The probable reasons for the
      decline are the widespread use of fluoride toothpaste, followed by artificial
      water fluoridation, oral health education and a slight decrease in sugar
      consumption overall. However, in regions without water fluoridation, fluoride
      supplementation for pregnant women may be an effective way to increase fluoride
      intake during pregnancy. If fluoride supplements taken by pregnant women improve
      neonatal outcomes, pregnant women with no access to a fluoridated drinking water
      supply can obtain the benefits of systemic fluoridation. OBJECTIVES: To evaluate
      the effects of women taking fluoride supplements (tablets, drops, lozenges or
      chewing gum) compared with no fluoride supplementation during pregnancy to
      prevent caries in the primary teeth of their children. SEARCH METHODS: Cochrane
      Oral Health's Information Specialist searched the following databases: Cochrane
      Oral Health's Trials Register (to 25 January 2017); the Cochrane Central Register
      of Controlled Trials (CENTRAL; 2016, Issue 11) in the Cochrane Library (searched
      25 January 2017); MEDLINE Ovid (1946 to 25 January 2017); Embase Ovid (1980 to 25
      January 2017); LILACS BIREME Virtual Health Library (Latin American and Caribbean
      Health Science Information database; 1982 to 25 January 2017); and CINAHL EBSCO
      (Cumulative Index to Nursing and Allied Health Literature; 1937 to 25 January
      2017). We searched the US National Institutes of Health Ongoing Trials Register
      (ClinicalTrials.gov) and the World Health Organization International Clinical
      Trials Registry Platform for ongoing trials to 25 January 2017. No restrictions
      were placed on the language or date of publication when searching the electronic
      databases. SELECTION CRITERIA: Randomised controlled trials (RCTs) of fluoride
      supplements (tablets, drops, lozenges or chewing gum) administered to women
      during pregnancy with the aim of preventing caries in the primary teeth of their
      children. DATA COLLECTION AND ANALYSIS: Two review authors independently screened
      the titles and abstracts (when available) of all reports identified through
      electronic searches. Two review authors independently extracted data and assessed
      risk of bias, as well as evaluating overall quality of the evidence utilising the
      GRADE approach. We could not conduct data synthesis as only one study was
      included in the analysis. MAIN RESULTS: Only one RCT met the inclusion criteria
      for this review. This RCT showed no statistical difference on decayed or filled
      primary tooth surfaces (dfs) and the percentage of children with caries at 3
      years (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.75 to 2.85;
      participants = 938, very low quality of evidence) and 5 years old (RR 0.84, 95%
      CI 0.53 to 1.33; participants = 798, very low quality of evidence). The incidence
      of fluorosis at 5 years was similar between the group taking fluoride supplements
      (tablets) during the last 6 months of pregnancy and the placebo group. AUTHORS'
      CONCLUSIONS: There is no evidence that fluoride supplements taken by women during
      pregnancy are effective in preventing dental caries in their offspring.

PMID- 29059465
TI  - What Is Old Is New Again: Delafloxacin, a Modern Fluoroquinolone.
AB  - Delafloxacin is a new fluoroquinolone antimicrobial approved for the treatment of
      acute bacterial skin and skin structure infections (ABSSSIs) in adults using
      dosage regimens of 300 mg intravenously every 12 hours, 450 mg orally every 12
      hours, or switching from intravenous to oral regimens for a 5- to 14-day
      treatment duration. Dosage adjustments in patients with severe renal dysfunction
      (estimated glomerular filtration rate [eGFR] = 15-29 ml/min/1.73 m2 ) are not
      required for oral doses but should be decreased to 200 mg intravenously every 12
      hours in patients requiring parenteral therapy. Due to insufficient data, use of
      delafloxacin is not recommended for patients on hemodialysis or with end-stage
      renal disease (eGFR < 15 ml/min/1.73 m2 ). Delafloxacin works through inhibition
      of DNA gyrase (topoisomerase II) and topoisomerase IV, which are essential
      enzymes for bacterial DNA transcription, replication, repair, and recombination
      and exhibits bactericidal activity against gram-positive and gram-negative
      organisms through a concentration-dependent matter. Delafloxacin has a very broad
      spectrum of activity against atypical, anaerobic, and resistant gram-negative and
      gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and
      Pseudomonas aeruginosa. During phase 3 trials, the most common side effects
      associated with delafloxacin were gastrointestinal (nausea, diarrhea). Unlike
      other fluoroquinolones, there does not seem to be a risk of QTc prolongation or
      phototoxicity with delafloxacin. The availability of both parenteral and oral
      formulations for delafloxacin distinguishes it from many of the currently
      available agents approved for ABSSSIs. Phase 3 studies for the treatment of
      respiratory infections are currently under way, and future results of these
      studies will further help delineate the role of delafloxacin.

PMID- 29059466
TI  - Increase in liver stiffness after transjugular intrahepatic portosystemic shunt
      is associated with inflammation and predicts mortality.
AB  - : Transjugular intrahepatic portosystemic shunt (TIPS) efficiently treats
      complications of portal hypertension. Liver and spleen stiffness might predict
      clinically significant portal hypertension. This prospective study investigated
      liver stiffness in patients receiving TIPS regardless of indication. Of 83
      included patients, 16 underwent transient elastography immediately before and 30
      minutes after TIPS (acute group), while 67 received shear wave elastography of
      liver and spleen 1 day before and 7 days after TIPS (chronic group) and were
      followed further. In blood samples obtained before TIPS from cubital, portal, and
      hepatic veins, levels of several interleukins (IL1b, IL6, IL8, IL10, IL18) and
      interferon-gamma were analyzed. In 27 patients (5 acute, 22 chronic), it resulted
      in an increase in liver stiffness of >10%. In 56 patients, liver stiffness
      decreased or remained unchanged (<10%). Importantly, spleen stiffness measured by
      shear wave elastography decreased in all patients (chronic group). None of the
      clinical or laboratory parameters differed between patients with increase in
      liver stiffness and those without. Of note, patients with increased liver
      stiffness showed higher overall and/or hepatic venous levels of proinflammatory
      cytokines at TIPS and higher incidence of organ failure and worse survival after
      TIPS. C-reactive protein values and increase of >10% in liver stiffness after
      TIPS were the only independent predictors of mortality in these patients.
      CONCLUSION: This study demonstrates that the presence of systemic inflammation
      predisposes patients to develop increased liver stiffness after TIPS, a predictor
      of organ failure and death. (NCT03072615) (Hepatology 2018;67:1472-1484).

PMID- 29059467
TI  - Telomere length and reactive oxygen species levels are positively associated with
      a high risk of mortality and recurrence in hepatocellular carcinoma.
AB  - : Telomeres protect chromosomal ends from deterioration and have been shown to be
      susceptible to shortening by reactive oxygen species (ROS)-induced damage. ROS
      levels increase during the progression from early to advanced hepatocellular
      carcinoma (HCC). An independent study found that the telomeres in most HCC
      tissues lengthened during carcinogenic advancement. Activated telomerase has been
      hypothesized to elongate telomeres during the progression of malignant HCC, but
      it remains unclear which signaling pathway is necessary for telomerase activation
      in HCC. Here, we showed using cell lines derived from human HCC that H2 O2 ,
      which is a major component of ROS in living organisms, elongates telomeres by
      increasing telomerase activity through protein kinase B (AKT) activation. The AKT
      inhibitor, perifosine, decreased telomere length, cellular viability, and H2 O2 
      mediated migration and invasion capacity in HCC cells while also inhibiting AKT
      activation, telomere maintenance, and tumor growth in nude mice. Advanced HCC
      tissues showed a positive correlation among ROS levels, phosphorylated AKT (pAKT)
      levels, and telomere length. Furthermore, patients with HCC tumors that have high
      ROS levels and long telomeres displayed poorer survival rates. These data
      demonstrate the significant utilities of ROS levels, pAKT levels, and telomere
      length for predicting a poor prognosis in patients with HCC. Taken together, AKT
      activation could be essential for telomere maintenance in advanced HCC tumors as
      well as being an important contributor to malignant HCC progression. CONCLUSION:
      We showed that H2 O2 contributes to telomere elongation through AKT activation in
      advanced HCC, suggesting that an AKT inhibitor such as perifosine may be useful
      for treating patients with malignant HCC. (Hepatology 2018;67:1378-1391).

PMID- 29059468
TI  - Hepatitis B virus sensitivity to interferon-alpha in hepatocytes is more
      associated with cellular interferon response than with viral genotype.
AB  - : Interferon-alpha (IFN-alpha) is used to treat chronic hepatitis B virus (HBV)
      infection, but only 20%-40% of patients respond well. Clinical observations have
      suggested that HBV genotype is associated with the response to IFN therapy;
      however, its role in viral responsiveness to IFN in HBV-infected hepatocytes
      remains unclear. Here, we produced infectious virions of HBV genotypes A to D to
      infect three well-recognized cell-culture-based HBV infection systems, including
      primary human hepatocytes (PHH), differentiated HepaRG (dHepaRG), and HepG2-NTCP
      cells to quantitatively compare the antiviral effect of IFN-alpha on HBV across
      genotypes and cell models. The efficacy of IFN-alpha against HBV in hepatocytes
      was generally similar across genotypes A2, B5, C2, and D3; however, it was
      significantly different among the infection models given that the half maximal
      inhibitory concentration value of IFN-alpha for inhibition of viral DNA
      replication in PHH (<20 U/mL) and dHepaRG cells were much lower than that in
      HepG2-NTCP cells (>500 U/mL). Notably, even in PHH, IFN-alpha did not reduce HBV
      covalently closed circular DNA at the concentrations for which viral antigens and
      DNA replication intermediates were strongly reduced. The three cell-culture
      models exhibited differential cellular response to IFN-alpha. The genes reported
      to be associated with responsiveness to IFN-alpha in patients were robustly
      induced in PHH while weakly induced in HepG2-NTCP cells upon IFN-alpha treatment.
      Reduction or promotion of IFN response in PHH or HepG2-NTCP cells significantly
      attenuated or improved the inhibitory capacity of IFN-alpha on HBV replication,
      respectively. CONCLUSION: In the cell-culture-based HBV infection models, the
      sensitivity of HBV to IFN-alpha in hepatocytes is determined more by the cell
      intrinsic IFN response than by viral genotype, and improvement of the IFN
      response in HepG2-NTCP cells promotes the efficacy of IFN-alpha against HBV.
      (Hepatology 2018;67:1237-1252).

PMID- 29059469
TI  - Fat-free muscle mass in magnetic resonance imaging predicts acute-on-chronic
      liver failure and survival in decompensated cirrhosis.
AB  - : Muscle mass seems to be a prognostic marker in patients with liver cirrhosis.
      However, reported methods to quantify muscle mass are heterogeneous, consented
      cutoff values are missing, and most studies have used computed tomography. This
      study evaluated fat-free muscle area (FFMA) as a marker of sarcopenia using
      magnetic resonance imaging (MRI) in patients with decompensated cirrhosis with
      transjugular intrahepatic portosystemic shunt (TIPS). The total erector spinae
      muscle area and the intramuscular fat tissue area were measured and subtracted to
      calculate the FFMA in 116 patients with cirrhosis by TIPS and MRI. The training
      cohort of 71 patients compared computed tomography-measured transversal psoas
      muscle thickness with FFMA. In 15 patients MRI was performed before and after
      TIPS, and in 12 patients follistatin serum measurements were carried out. The
      results on FFMA were confirmed in a validation cohort of 45 patients. FFMA
      correlated with follistatin and transversal psoas muscle thickness and showed
      slightly better association with survival than transversal psoas muscle
      thickness. Gender-specific cutoff values for FFMA were determined for sarcopenia.
      Decompensation (ascites, overt hepatic encephalopathy) persisted after TIPS in
      the sarcopenia group but resolved in the nonsarcopenia group. Sarcopenic patients
      showed no clinical improvement after TIPS as well as higher mortality, mainly due
      to development of acute-on-chronic liver failure. FFMA was an independent
      predictor of survival in these patients. CONCLUSION: This study offers an easy-to
      apply MRI-based measurement of fat-free muscle mass as a marker of sarcopenia in
      decompensated patients; while TIPS might improve sarcopenia and thereby survival,
      persistence of sarcopenia after TIPS is associated with a reduced response to
      TIPS and a higher risk of acute-on-chronic liver failure development and
      mortality. (Hepatology 2018;67:1014-1026).

PMID- 29059471
TI  - Preparation and evaluation of a chiral HPLC stationary phase based on cone
      calix[4]arene functionalized at the upper rim with l-alanine units.
AB  - Here we report a new chiral stationary phase (CSP) immobilized on silica gel
      based on cone calix[4]arene functionalized at the upper rim with two l-alanine
      units as new chiral selector that has been used in high-performance liquid
      chromatography. The CSP was prepared by covalently bonding the allyl groups at
      the lower rim of calix[4]arene to silica gel by thiol-ene click chemistry
      reaction. Elemental analysis of the CSP showed that 120 MUmol of chiral selector
      bonded per gram of silica gel. 1-Hexene was used for end-capping of unreacted
      mercapto groups on silica gel. Since the CSP is chemically bonded to the silica,
      it can be used in the normal-phase and reversed-phase mode and with halogenated
      solvents as mobile phases, if desired. The chromatographic performance of the CSP
      was evaluated in the enantioseparation of the 3,5-dinitrobenzoyl derivatives of
      some amino acids, diclofop-methyl and dl-mandelic acid.

PMID- 29059470
TI  - Barrier to autointegration factor 1, procollagen-lysine, 2-oxoglutarate 5
      dioxygenase 3, and splicing factor 3b subunit 4 as early-stage cancer decision
      markers and drivers of hepatocellular carcinoma.
AB  - : An accurate tool enabling early diagnosis of hepatocellular carcinoma (HCC) is
      clinically important, given that early detection of HCC markedly improves
      survival. We aimed to investigate the molecular markers underlying early
      progression of HCC that can be detected in precancerous lesions. We designed a
      gene selection strategy to identify potential driver genes by integrative
      analysis of transcriptome and clinicopathological data of human multistage HCC
      tissues, including precancerous lesions, low- and high-grade dysplastic nodules.
      The gene selection process was guided by detecting the selected molecules in both
      HCC and precancerous lesion. Using various computational approaches, we selected
      10 gene elements as a candidate and, through immunohistochemical staining, showed
      that barrier to autointegration factor 1 (BANF1), procollagen-lysine, 2
      oxoglutarate 5-dioxygenase 3 (PLOD3), and splicing factor 3b subunit 4 (SF3B4)
      are HCC decision markers with superior capability to diagnose early-stage HCC in
      a large cohort of HCC patients, as compared to the currently popular trio of HCC
      diagnostic markers: glypican 3, glutamine synthetase, and heat-shock protein 70.
      Targeted inactivation of BANF1, PLOD3, and SF3B4 inhibits in vitro and in vivo
      liver tumorigenesis by selectively modulating epithelial-mesenchymal transition
      and cell-cycle proteins. Treatment of nanoparticles containing small-interfering
      RNAs of the three genes suppressed liver tumor incidence as well as tumor growth
      rates in a spontaneous mouse HCC model. We also demonstrated that SF3B4
      overexpression triggers SF3b complex to splice tumor suppressor KLF4 transcript
      to nonfunctional skipped exon transcripts. This contributes to malignant
      transformation and growth of hepatocyte through transcriptional inactivation of
      p27Kip1 and simultaneously activation of Slug genes. CONCLUSION: The findings
      suggest molecular markers of BANF1, PLOD3, and SF3B4 indicating early-stage HCC
      in precancerous lesion, and also suggest drivers for understanding the
      development of hepatocarcinogenesis. (Hepatology 2018;67:1360-1377).

PMID- 29059472
TI  - Adding care to cure for patients with liver disease: A cultural shift.

PMID- 29059474
TI  - Ducts in a dish: Bioengineered biliary scaffolds for regenerative medicine.

PMID- 29059473
TI  - Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review
      25.
AB  - The calcitonin/CGRP family of peptides includes calcitonin, alpha and beta CGRP,
      amylin, adrenomedullin (AM) and adrenomedullin 2/intermedin (AM2/IMD). Their
      receptors consist of one of two GPCRs, the calcitonin receptor (CTR) or the
      calcitonin receptor-like receptor (CLR). Further diversity arises from
      heterodimerization of these GPCRs with one of three receptor activity-modifying
      proteins (RAMPs). This gives the CGRP receptor (CLR/RAMP1), the AM1 and AM2
      receptors (CLR/RAMP2 or RAMP3) and the AMY1, AMY2 and AMY3 receptors (CTR/RAMPs1
      3 complexes, respectively). Apart from the CGRP receptor, there are only peptide
      antagonists widely available for these receptors, and these have limited
      selectivity, thus defining the function of each receptor in vivo remains
      challenging. Further challenges arise from the probable co-expression of CTR with
      the CTR/RAMP complexes and species-dependent splice variants of the CTR (CT(a)
      and CT(b) ). Furthermore, the AMY1(a) receptor is activated equally well by both
      amylin and CGRP, and the preferred receptor for AM2/IMD has been unclear.
      However, there are clear therapeutic rationales for developing agents against the
      various receptors for these peptides. For example, many agents targeting the CGRP
      system are in clinical trials, and pramlintide, an amylin analogue, is an
      approved therapy for insulin-requiring diabetes. This review provides an update
      on the pharmacology of the calcitonin family of peptides by members of the
      corresponding subcommittee of the International Union of Basic and Clinical
      Pharmacology and colleagues.

PMID- 29059476
TI  - Influence of Apolipoprotein E polymorphism on susceptibility of Wilson disease.
AB  - Wilson disease (WD) is an autosomal-recessive disorder caused by mutations in the
      ATP7B gene leading to abnormal copper deposition in liver and brain. WD manifests
      diverse neurological and hepatic phenotypes and different age of onset, even
      among the siblings, with same mutational background suggesting complex nature of
      the disease and involvement of other candidate genes. In that context,
      Apolipoprotein E (APOE) and Prion Protein (PRNP) have been proposed to be
      potential candidates for modifying the WD phenotype and age of onset. This study
      aims to identify the contribution of APOE and PRNP polymorphisms on the variable
      phenotypic expression of Indian WD patients. A total of 171 WD patients and 291
      controls from Indian population were included in this study. Two APOE cSNPs
      (rs429358 and rs7412) resulting in three isoforms and M129V (rs1799990)
      polymorphism of PRNP were examined for their association with WD and its clinical
      phenotypes. The APOE ?4 allele was found to be significantly overrepresented in
      WD patients compared to controls. However, the frequency of the APOE ?3 allele
      and ?3/?3 genotype was significantly higher in WD patients without cognitive
      behavior impairment compared to the ones with the impairment. On the contrary,
      the PRNP allele representing Val129 was found to be present in higher proportion
      in WD patients with cognitive behavioral decline. Our data suggest that the APOE
      ?4 allele could act as a potential risk for the pathogenesis of WD. Also, APOE
      and PRNP might contribute toward the cognitive behavioral decline in a section of
      WD patients.

PMID- 29059475
TI  - Incidence of and Risk Factors for Severe Adverse Events in Elderly Patients
      Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor
      Blockers after an Acute Myocardial Infarction.
AB  - STUDY OBJECTIVE: To assess the incidence of and risk factors associated with
      severe adverse events in elderly patients who used angiotensin-converting enzyme
      inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) after an acute
      myocardial infarction (AMI). DESIGN: Retrospective cohort study. DATA SOURCES:
      Centers for Medicare & Medicaid Services Chronic Conditions Data Warehouse
      (Medicare service claims database), American Community Survey of the U.S. Census
      Bureau, and Multum Lexicon Drug database. PATIENTS: A total of 101,588 eligible
      Medicare fee-for-service beneficiaries 66 years or older, who were hospitalized
      for AMI between January 1, 2008, and December 31, 2009, and used ACEIs or ARBs
      within 30 days after discharge. MEASUREMENTS AND MAIN RESULTS: Primary outcomes
      were hospitalizations for acute renal failure (ARF) and hyperkalemia. The
      secondary outcome was discontinuation or suspension of ACEI/ARB therapy after a
      visit to a health care provider. The primary risk factors of interest were age,
      sex, race/ethnicity, and chronic kidney disease (CKD). Cumulative incidence
      curves and multivariable Fine-Gray proportional hazards models with 95%
      confidence intervals (CIs) were used with death as a competing risk in both
      intention-to-treat (ITT) and as-treated (AT) analyses. In the study cohort, 2.8%
      experienced ARF, 0.5% experienced hyperkalemia, and 63.7% discontinued ACEI/ARB
      therapy within 1 year after hospital discharge. Approximately half of the
      incidence of ARF and hyperkalemia occurred within 6 months after hospital
      discharge, but the cumulative incidence increased after 6 months. Patients older
      than 85 years had a higher rate of ARF (ITT hazard ratio [HR] 1.15, 95% CI 1.04
      1.28) and hyperkalemia (ITT HR 1.33, 95% CI 1.05-1.68) compared with those aged
      65-74 years. Patients with baseline CKD had higher rates of ARF (ITT HR 1.61, 95%
      CI 1.42-1.82), hyperkalemia (ITT HR 1.41, 95% CI 1.11-1.77), and ACEI/ARB therapy
      discontinuation or suspension (ITT HR 1.05, 95% CI 1.02-1.09). CONCLUSION: We
      found a low incidence of ARF and hyperkalemia in elderly patients treated with
      ACEIs or ARBs after AMI hospitalization. However, a high rate of treatment
      discontinuation might prevent a higher rate of occurrence of these events. Long
      term careful monitoring of severe adverse events and timely discontinuation of
      ACEIs or ARBs among elderly patients with advancing age and CKD after an AMI is
      warranted in clinical practice.

PMID- 29059477
TI  - Interdependency of efficient nodulation and arbuscular mycorrhization in
      Piptadenia gonoacantha, a Brazilian legume tree.
AB  - Tripartite interactions between legumes and their root symbionts (rhizobia and
      arbuscular mycorrhizal fungi, AMF) are poorly understood, although it is well
      established that only specific combinations of symbionts lead to optimal plant
      growth. A classic example in which to investigate such interactions is the
      Brazilian legume tree Piptadenia gonoacantha (Caesalpinioideae), for which
      efficient nodulation has been described as dependent on the presence of AMF
      symbiosis. In this study, we compared the nodulation behaviour of several
      rhizobial strains with or without AMF inoculation, and performed analyses on
      nodulation, nodule cytology, N-fixing efficiency, and plant growth response.
      Nodulation of P. gonoacantha does not rely on the presence of AMF, but
      mycorrhization was rhizobial strain-dependent, and nodule effectiveness and plant
      growth were dependent on the presence of specific combinations of rhizobial
      strains and AMF. The co-occurrence of both symbionts within efficient nodules and
      the differentiation of bacteroids within nodule cells were also demonstrated.
      Novel close interactions and interdependency for the establishment and/or
      functioning of these symbioses were also revealed in Piptadenia, thanks to
      immunocytochemical analyses. These data are discussed in terms of the
      evolutionary position of the newly circumscribed mimosoid clade within the
      Caesalpinioid subfamily and its relative proximity to non-nodulated (but AMF
      associated) basal subfamilies.

PMID- 29059478
TI  - Does water temperature influence the performance of key survival skills?
AB  - Aquatic survival skills may be compromised in cold water thereby increasing the
      likelihood of drowning. This study compared physiological, psychological, and
      behavioral responses of humans treading water and swimming in cold and temperate
      water. Thirty-eight participants were classified as inexperienced (n = 9),
      recreational (n = 15), or skilled (n = 10) swimmers. They performed 3 tasks:
      treading water (120 seconds), swim at "comfortable" pace, and swim at "fast" pace
      in 2 water conditions (28 degrees C vs 10 degrees C). Heart rate, oxygen uptake,
      psychometric variables, spatio-temporal (swim speed, stroke rate, and stroke
      length), and coordination type were examined as a function of expertise. Tasks
      performed in cold water-generated higher cardiorespiratory responses (HR = 145 +/
      16 vs 127 +/- 21 bpm) and were perceived about 2 points more strenuous on the
      Borg scale on average (RPE = 14.9 +/- 2.8 vs 13.0 +/- 2.0). The voluntary
      durations of both treading water (60 +/- 32 vs 91 +/- 33 seconds) and swimming at
      a comfortable pace (66 +/- 22 vs 103 +/- 34 seconds) were significantly reduced
      in cold water. However, no systematic changes in movement pattern type could be
      determined in either the treading water task or the swimming tasks. Water
      temperature influences the physical demands of these aquatic skills but not
      necessarily the behavior. Training treading water and swimming skills in
      temperate water seems to transfer to cold water, but we recommend training these
      skills in a range of water conditions to help adapt to the initial "cold-shock"
      response.

PMID- 29059479
TI  - Anti-TNF therapy is not associated with an increased risk of post-colectomy
      complications, a population-based study.
AB  - AIM: Previous studies have raised concerns that the use of anti-tumour necrosis
      factor (anti-TNF) therapy in patients with ulcerative colitis (UC) undergoing
      surgery may increase the risk of postoperative complications. We have taken a
      population-based approach to investigate whether there is an association between
      anti-TNF therapy and postoperative complications in UC patients undergoing
      subtotal colectomy. METHOD: Hospital Episode Statistics (HES) data and procedural
      coding were used to identify all patients in England between April 2006 and March
      2015 undergoing subtotal colectomy for UC. Patients were grouped into those who
      received anti-TNF therapy within 12 or 4 weeks of surgery and those who did not.
      The incidence of postoperative complications was evaluated by HES coding and
      compared between groups. RESULTS: In all, 6225 UC patients underwent subtotal
      colectomy. 753 patients received anti-TNF therapy within 12 weeks prior to
      surgery (418 within 4 weeks). There was no difference in postoperative
      complications between groups although groups were not comparable for age and
      comorbidities. Logistic regression with complications as the outcome variable did
      not show any significant association between anti-TNF therapy and complications.
      Colectomy performed during an unplanned admission (vs planned admission) and
      smoking were associated with complications. CONCLUSION: This large population
      based study does not demonstrate any association between preoperative anti-TNF
      therapy and postoperative complications in UC patients undergoing subtotal
      colectomy. The only variables associated with complications were colectomy
      performed during an unplanned admission and smoking.

PMID- 29059480
TI  - Renal insufficiency mimicking glutaric acidemia type 1 on newborn screening.
AB  - BACKGROUND: Glutaryl carnitine (C5DC) in dried blood spots is used as a biomarker
      for glutaric aciduria type 1 (GA-1) screening. C5DC, however, is the only
      screening marker for this condition, and various pathological conditions may
      interfere with C5DC metabolism. Recently, C5DC elevation has been reported in
      cases of renal insufficiency. METHOD: Five patients who were positive for GA-1 on
      newborn screening with tandem mass spectrometry between September 2012 and March
      2015 at Kobe University Hospital were enrolled in this study. RESULTS: GA-1 was
      not confirmed on urinary organic acids analysis in any of the patients. C5DC
      decreased immediately in four patients, but one patient, who had high C5DC for at
      least 4 months, was diagnosed with bilateral renal hypoplasia. CONCLUSION: In the
      case of persistently elevated C5DC, renal insufficiency should be considered as a
      differential diagnosis.

PMID- 29059482
TI  - Bioinspired Nanocomposite Hydrogels with Highly Ordered Structures.
AB  - In the human body, many soft tissues with hierarchically ordered composite
      structures, such as cartilage, skeletal muscle, the corneas, and blood vessels,
      exhibit highly anisotropic mechanical strength and functionality to adapt to
      complex environments. In artificial soft materials, hydrogels are analogous to
      these biological soft tissues due to their "soft and wet" properties, their
      biocompatibility, and their elastic performance. However, conventional hydrogel
      materials with unordered homogeneous structures inevitably lack high mechanical
      properties and anisotropic functional performances; thus, their further
      application is limited. Inspired by biological soft tissues with well-ordered
      structures, researchers have increasingly investigated highly ordered
      nanocomposite hydrogels as functional biological engineering soft materials with
      unique mechanical, optical, and biological properties. These hydrogels
      incorporate long-range ordered nanocomposite structures within hydrogel network
      matrixes. Here, the critical design criteria and the state-of-the-art fabrication
      strategies of nanocomposite hydrogels with highly ordered structures are
      systemically reviewed. Then, recent progress in applications in the fields of
      soft actuators, tissue engineering, and sensors is highlighted. The future
      development and prospective application of highly ordered nanocomposite hydrogels
      are also discussed.

PMID- 29059481
TI  - Neonatal Eating Outcome Assessment: tool development and inter-rater reliability.
AB  - AIM: To define the process of tool development and revision for the Neonatal
      Eating Outcome (NEO) Assessment and to report preliminary inter-rater
      reliability. METHODS: Tool development consisted of a review of the literature
      and observations of feeding performance among 178 preterm infants born <=32 weeks
      gestation. 11 neonatal therapy feeding experts provided structured feedback to
      establish content validity and define the scoring matrix. The tool was then used
      to evaluate feeding in 50 preterm infants born <=32 weeks of gestation and 50
      full-term infants. Multiple revisions occurred at each stage of development.
      Finally, six neonatal occupational therapists participated in reliability testing
      by independently scoring five videos of oral feeding of preterm infants using
      version 4 of the tool. RESULTS: The intraclass correlation for the 'prefeeding'
      score was 0.71 (0.37-0.96), and the intraclass correlation for the 'total' score
      was 0.83 (0.56-0.98). CONCLUSION: The 'total' score had good to excellent
      reliability. Fleiss' Kappa scores for all 18 scorable items ranged from slight
      agreement to moderate agreement. Items with the lowest Kappa scores were revised,
      and additional feedback from therapists engaged in reliability testing was
      incorporated, resulting in final version 5.

PMID- 29059483
TI  - Surgical management of colonic basidiobolomycosis among adolescent and adult
      patients: presentation and outcome.
AB  - AIM: The aim of this study was to review retrospectively the clinical
      presentations, indications for surgery and surgical outcomes of adolescent and
      adult patients who were diagnosed with colonic basidiobolomycosis in the last 10
      years. METHOD: The study was carried out in Aseer Central Hospital, Abha, Saudi
      Arabia by reviewing the medical files of all patients in the last 10 years who
      were diagnosed with colonic basidiobolomycosis and required surgical
      intervention. RESULTS: There were 22 patients. Common findings in all patients
      were weight loss, abdominal pain and an abdominal mass. The right colon was
      affected in 21 patients. The initial diagnosis was correct in seven patients
      while nine were thought to be malignant. All patients underwent colonic resection
      followed by at least 1 year of antifungal medical treatment. Intra-operatively,
      all patients had moderate or dense adhesions, an abdominal mass and
      lymphadenopathy. Most surgeons had the impression intra-operatively that the
      diagnosis was inflammatory rather than malignant. Postoperatively, three patients
      died within 6 months of the operation due to progression of the disease. Four
      patients developed severe wound infections, three of whom had abdominal
      dehiscence and required re-closure. CONCLUSION: Colonic basidiobolomycosis is a
      life-threatening fungal infection that should be considered a surgical condition.
      A high index of suspicion including basidiobolomycosis in the differential
      diagnosis for the acute abdomen with a colonic mass is required for a proper
      diagnosis. Early aggressive surgical management followed by a prolonged course of
      itraconazole postoperatively could improve the outcome of the condition.

PMID- 29059484
TI  - Imaging characteristics of papillary muscle site of origin of ventricular
      arrhythmias in patients with mitral valve prolapse.
AB  - BACKGROUND: Mitral valve prolapse has been associated with increased risk of
      ventricular arrhythmias. We aimed to examine whether certain cardiac imaging
      characteristics are associated with papillary muscle origin of ventricular
      arrhythmias in these patients. METHODS AND RESULTS: We screened electronic
      medical records of all patients documented to have mitral valve prolapse on
      either transthoracic echocardiogram (TTE) or cardiac magnetic resonance imaging
      (CMR) in our center, who also underwent an electrophysiologic study (EPS) between
      2007 and 2016. Anterior and posterior mitral leaflet thickness and prolapsed
      distance were measured on TTE and late gadolinium enhancement (LGE) was assessed
      on CMR. Patients were categorized as papillary muscle positive (pap (+)) or
      negative (pap (-)) using EPS. Eighteen patients were included in this study. Of
      the 15 patients who underwent TTE, a significantly higher proportion of patients
      in the pap (+) group had an anterior to posterior leaflet prolapse ratio of >0.45
      indicating more symmetric leaflet prolapse. There were no differences in anterior
      or posterior leaflet thickness or prolapse distance between the groups. Patients
      in the pap (+) group were more likely to be women. Of the 7 patients who
      underwent CMR, those who were pap (+) were more likely to have LGE in the region
      of the papillary muscles than those who were pap (-). CONCLUSION: Female gender,
      more symmetric bileaflet prolapse on TTE, and the presence of papillary muscle
      LGE on CMR may be associated with papillary muscle origin of ventricular
      arrhythmias in patients with mitral valve prolapse.

PMID- 29059486
TI  - Skin-to-skin hospital transfers are physiologically sound and empower parents.

PMID- 29059485
TI  - Clinical assessment and comparison of annotation algorithms in high-density
      mapping of regular atrial tachycardias.
AB  - BACKGROUND: High-density automated mapping of regular atrial tachycardias (ATs)
      requires accurate assessment of local activation times (LATs). OBJECTIVE: To
      evaluate high-density mapping of ATs and compare the accuracy of different
      automated LAT annotation algorithms. METHODS: Fifteen patients underwent AT
      ablation guided by the automated ConfiDENSE? high-density mapping module (Carto 3
      v4) allowing manual reannotation (edited maps). For each AT, unedited automated
      maps were reconstructed offline by three algorithms: maximum unipolar slope
      (LATSlope ), bipolar peak (LATPeak ), and a new hybrid annotation algorithm
      (LATHybrid ). Five blinded experts were asked to define the (1) tachycardia
      mechanism, (2) ablation target, and (3) level of difficulty of these unedited
      maps. RESULTS: Twenty-one ATs (cycle length 300 +/- 46 ms, activation points 955
      +/- 421) were successfully ablated using LATHybrid guided ablation with manual
      editing in a small number of points. At 6 months, 14 (93%) of the patients were
      free of AT recurrences. Unedited LATHybrid maps showed the highest accuracy in
      defining the tachycardia mechanism (LATHybrid : 49% vs. LATPeak : 27% vs.
      LATSlope : 28%, P < 0.001) and ablation target (LATHybrid : 65% vs. LATPeak : 39%
      vs. LATSlope : 31%, P < 0.001). Overall, LATHybrid -annotated maps were graded as
      "easier to interpret" by the experts (difficulty score 2.3 +/- 0.9) versus
      LATPeak (2.8 +/- 1) and LATSlope (3.2 +/- 0.8) (P < 0.001). Only 12% of the
      LATHybrid maps were annotated as uninterpretable compared to 31% of LATSlope and
      45% of the LATPeak maps (P < 0.001). CONCLUSION: Automated LATHybrid annotation
      allows better and easier recognition of the tachycardia mechanism compared to
      automated LATPeak and LATSlope algorithms, although fully automated mapping still
      requires further improvements.

PMID- 29059487
TI  - From childhood adversity to problem behaviors: Role of psychological and
      structural social integration.
AB  - BACKGROUND: Childhood adversity (CA) is associated with problem behaviors in
      adolescence, but the mediators, that is, those factors that help build resilience
      and prevent some children who experience CA from engaging in problem behaviors,
      await more exploration, including social integration. The aim of this study was
      to identify the association between CA and adolescent problem behaviors, and to
      further examine the mediating role of social integration distinctly as
      psychological and structural integration. METHODS: Data used were from the Taiwan
      Education Panel Survey, a core panel of 4,261 students (age 13) surveyed in 2001
      and followed for three more waves until age 18. For psychological integration, an
      average score was calculated to represent adolescents' feelings about their
      school. Structural integration was constructed using several items about
      adolescents' school and extracurricular activities. We used structural equation
      modeling with the diagonally weighted least squares method to examine the effect
      of CA on the primary outcome: adolescent problem behaviors via social
      integration. RESULTS: The hypothesized structural equation model specifying the
      path from CA to adolescent problem behavior had good fit. Respondents with one CA
      were indirectly linked to problem behaviors via psychological but not structural
      integration (e.g. the level of participation in school and non-school
      activities). On mediation analysis, psychological integration significantly
      mediated the paths from one CA to all six problem behaviors (all P < 0.05).
      CONCLUSION: The presence of only one CA was indirectly associated with problem
      behavior via psychological integration; two or more CA were not associated with
      significant paths to problem behaviors. The contribution of social integration is
      crucial to an adolescent's development from CA to problem behaviors. To form
      supportive social relationships to achieve better health, we suggest that those
      adolescents who have been exposed to CA should be helped to join more teams and
      take part in more activities, thereby increasing their opportunities for social
      interaction, and improving their communication skills.

PMID- 29059488
TI  - Stereoelectroencephalography and surgical outcome in polymicrogyria-related
      epilepsy: A multicentric study.
AB  - OBJECTIVE: We aimed to (1) assess the concordance between various polymicrogyria
      (PMG) types and the associated epileptogenic zone (EZ), as defined by
      stereoelectroencephalography (SEEG), and (2) determine the postsurgical seizure
      outcome in PMG-related drug-resistant epilepsy. METHODS: We retrospectively
      analyzed 58 cases: 49 had SEEG and 39 corticectomy or hemispherotomy. RESULTS:
      Mean age at SEEG or surgery was 28.3 years (range, 2-50). PMG was bilateral in 9
      (16%) patients and unilateral in 49, including 17 (29%) unilobar, 12 (21%)
      multilobar, 15 (26%) perisylvian, and only 5 (9%) hemispheric. Twenty-eight (48%)
      patients additionally had schizencephaly, heterotopia, or focal cortical
      dysplasia. The SEEG-determined EZ was fully concordant with the PMG in only 8
      (16%) cases, partially concordant in 74%, and discordant in 10%. The EZ included
      remote cortical areas in 21 (43%) cases and was primarily localized in those in 5
      (10%), all related to the mesial temporal structures. All but 1 PMG patient with
      corticectomy or hemispherotomy had a unilateral PMG. At last follow-up (mean, 4.6
      years; range, 1-16), 28 (72%) patients remained seizure free. Shorter epilepsy
      duration to surgery was an independent predictor of seizure freedom.
      INTERPRETATION: PMG-related drug-resistant epilepsy warrants a comprehensive
      presurgical evaluation, including SEEG investigations in most cases, given that
      the EZ may only partially overlap with the PMG or include solely remote cortical
      areas. Seizure freedom is feasible in a large proportion of patients. PMG extent
      should not deter from exploring the possibility of epilepsy surgery. Our data
      support the early consideration of epilepsy surgery in this patient group. Ann
      Neurol 2017;82:781-794.

PMID- 29059489
TI  - Risk factors for anastomotic leakage following ileosigmoid or ileorectal
      anastomosis.
AB  - AIM: Reconstruction with an ileosigmoidal anastomosis (ISA) or ileorectal
      anastomosis (IRA) is a surgical option after a subtotal colectomy. Anastomotic
      leakage (AL) is a problematic complication and high rates have been reported, but
      there is limited understanding of the risk factors involved. The aim of this
      study was to assess the established and potential predictors of AL following ISA
      and IRA. METHOD: This was a retrospective cohort study including all patients who
      had undergone ISA or IRA at three Swedish referral centres for colorectal surgery
      between January 2007 and March 2015. Data regarding clinical characteristics,
      treatment and outcome were collected from medical records. Univariate and
      multivariate logistic regression models were used to determine the association
      between patient and treatment related factors and the cumulative incidence of AL.
      RESULTS: In total, 227 patients were included. Overall, AL was detected amongst
      30 patients (13.2%). Amongst patients undergoing colectomy with synchronous ISA
      or IRA (one-stage procedure), AL occurred in 23 out of 120 (19.2%) compared with
      seven out of 107 (6.5%) after stoma reversal with ISA or IRA (two-stage
      procedure) (P = 0.004). In addition, the multivariate analyses revealed a
      statistically significantly lower odds ratio for AL following a two-stage
      procedure (OR 0.10, 95% CI 0.03-0.41, P = 0.001). CONCLUSIONS: This study
      confirms high rates of AL following ISA and IRA. In particular, a synchronous
      procedure with colectomy and ISA/IRA carries a high risk of AL.

PMID- 29059490
TI  - What we do in neonatal analgesia overshadows how we do it.

PMID- 29059491
TI  - Does smoking impact dopamine neuronal loss in de novo Parkinson disease?
AB  - This study analyzed data from dopamine transporter (DAT) positron emission
      tomographic scans of 282 male patients with de novo Parkinson disease to
      investigate whether smoking impacts striatal dopamine neuronal degeneration. Mean
      DAT activity in the posterior (p = 0.016) and ventral putamen (p = 0.028) was
      higher in 44 current smokers in comparison to 105 ex-smokers and 133 never
      smokers. The severity of baseline motor deficits and the longitudinal increases
      in levodopa-equivalent doses during follow-up were similar among the 3 groups.
      These results suggest that current smoking, but not past smoking, protects
      dopamine neuronal degeneration in the sensorimotor striatum with no additional
      clinical benefits. Ann Neurol 2017;82:850-854.

PMID- 29059492
TI  - Phase I study of single-agent ribociclib in Japanese patients with advanced solid
      tumors.
AB  - The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers.
      Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary
      clinical activity in a phase I study in the USA and Europe for patients with
      solid tumors and lymphomas. The present study aimed to determine the single-agent
      maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese
      patients with advanced solid tumors. Ribociclib safety, tolerability,
      pharmacokinetic profile, and preliminary antitumor activity were also assessed.
      Japanese patients with solid tumors that had progressed on prior therapies
      received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off
      schedule. Treatment continued until the development of toxicity or disease
      progression. A dose escalation was planned for patients with esophageal cancer.
      In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13
      patients received 600 mg ribociclib. Four patients experienced dose-limiting
      toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600
      mg, and the MTD was not determined. The most frequent adverse events were
      hematologic and gastrointestinal. Four patients achieved stable disease at the
      600 mg dose; no patients achieved complete or partial response. All patients
      discontinued the study, the majority due to disease progression. No patients
      discontinued due to adverse events. Dose escalation was not pursued due to lack
      of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks
      on/1-week-off schedule, ribociclib showed acceptable safety and tolerability
      profiles in Japanese patients with advanced solid tumors.

PMID- 29059493
TI  - Wakayama Medical University Hospital perinatal helicopter ambulance service: 14
      year review.
AB  - BACKGROUND: In 2003, a perinatal helicopter air ambulance service was introduced
      for remote areas of Wakayama and Mie prefectures, Japan, but its long-term impact
      on perinatal medicine has not yet been analyzed. METHODS: A retrospective
      observational study was conducted on helicopter air ambulance cases recorded
      between January 2003 and December 2016 at Wakayama Medical University Hospital
      (WMUH). RESULTS: During that period, 61 pregnant mothers were transferred by
      helicopter air ambulance to WMUH. Between 2003 and 2009, the mean period from
      transfer to birth was 0.6 weeks, whereas between 2008 and 2016, this increased to
      1.6 weeks, and the survival rate of infants born after transfer did not differ
      significantly (84.2%, 32/38 versus 82.1%, 23/28). Seventy-three neonates were
      transferred. The number transferred between 2003 and 2009 was 46, whereas this
      decreased to 27 between 2010 and 2016. The neonatal mortality rate in south
      Wakayama plus south Mie gradually decreased. The reasons for the longer period
      from transfer to birth, and the decrease in the rate of very low-birthweight
      infants after transfer may be due to development in the management of threatened
      premature labor, and the earlier transfer of such cases by regional
      obstetricians. The reasons for the decline in neonatal transfer may have included
      the development of fetal diagnostic techniques and improved efficiency of
      neonatal ground-transport in the South Wakayama region. CONCLUSION: The
      helicopter air ambulance is an important form of medical transportation in the
      south Kii peninsula.

PMID- 29059494
TI  - Molecular-based diagnosis of multiple sclerosis and its progressive stage.
AB  - OBJECTIVE: Biomarkers aid diagnosis, allow inexpensive screening of therapies,
      and guide selection of patient-specific therapeutic regimens in most internal
      medicine disciplines. In contrast, neurology lacks validated measurements of the
      physiological status, or dysfunction(s) of cells of the central nervous system
      (CNS). Accordingly, patients with chronic neurological diseases are often treated
      with a single disease-modifying therapy without understanding patient-specific
      drivers of disability. Therefore, using multiple sclerosis (MS) as an example of
      a complex polygenic neurological disease, we sought to determine whether
      cerebrospinal fluid (CSF) biomarkers are intraindividually stable, cell type-,
      disease- and/or process-specific, and responsive to therapeutic intervention.
      METHODS: We used statistical learning in a modeling cohort (n = 225) to develop
      diagnostic classifiers from DNA-aptamer-based measurements of 1,128 CSF proteins.
      An independent validation cohort (n = 85) assessed the reliability of derived
      classifiers. The biological interpretation resulted from in vitro modeling of
      primary or stem cell-derived human CNS cells and cell lines. RESULTS: The
      classifier that differentiates MS from CNS diseases that mimic MS clinically,
      pathophysiologically, and on imaging achieved a validated area under the receiver
      operating characteristic curve (AUROC) of 0.98, whereas the classifier that
      differentiates relapsing-remitting from progressive MS achieved a validated AUROC
      of 0.91. No classifiers could differentiate primary progressive from secondary
      progressive MS better than random guessing. Treatment-induced changes in
      biomarkers greatly exceeded intraindividual and technical variabilities of the
      assay. INTERPRETATION: CNS biological processes reflected by CSF biomarkers are
      robust, stable, disease specific, or even disease stage specific. This opens
      opportunities for broad utilization of CSF biomarkers in drug development and
      precision medicine for CNS disorders. Ann Neurol 2017;82:795-812.

PMID- 29059495
TI  - 2D Spherulites of a Semi-Fluorinated Alkane: Controlled Access to Either Radial
      Or Ring-Banded Morphologies.
AB  - Thin films of a semi-fluorinated alkane cast onto solid substrates consist of
      well-formed two-dimensional non-birefringent ring-banded and/or radial
      spherulites. Controlling the experimental conditions allows orientation of the
      crystallization toward either radial-only or ring-banded-only morphologies.
      Intermediate states were also captured in which both radial and ring-banded
      spherulites coexist. Monitoring of the formation of these intermediate states
      brought evidence for a first crystallization mode that sweeps radially outwards
      from a central nucleus until the propagating front edge experiences a second
      crystallization mode that proceeds through a diffusion-controlled rhythmic
      crystallization mechanism that leads to high (~2 MUm) concentric ridges. These 2D
      spherulites were investigated by optical and atomic force microscopies,
      interferometric profilometry, and off-specular neutron scattering.

PMID- 29059496
TI  - Increased T-helper 17 cell differentiation mediated by exosome-mediated microRNA
      451 redistribution in gastric cancer infiltrated T cells.
AB  - MicroRNA (miR)-451 is a cell metabolism-related miRNA that can mediate cell
      energy-consuming models by several targets. As miR-451 can promote mechanistic
      target of rapamycin (mTOR) activity, and increased mTOR activity is related to
      increased differentiation of T-helper 17 (Th17) cells, we sought to investigate
      whether miR-451 can redistribute from cancer cells to infiltrated T cells and
      enhance the distribution of Th17 cells through mTOR. Real-time PCR was used for
      detecting expression of miR-451 in gastric cancer, tumor infiltrated T cells and
      exosomes, and distribution of Th17 was evaluated by both flow cytometry and
      immunohistochemistry (IHC). Immunofluorescence staining was used in monitoring
      the exosome-enveloped miR-451 from cancer cells to T cells with different
      treatments, and signaling pathway change was analyzed by western blot. miR-451
      decreased significantly in gastric cancer (GC) tissues but increased in
      infiltrated T cells and exosomes; tumor miR-451 was negatively related to
      infiltrated T cells and exosome miR-451. Exosome miR-451 can not only serve as an
      indicator for poor prognosis of post-operation GC patients but is also related to
      increased Th17 distribution in gastric cancer. miR-451 can redistribute from
      cancer cells to T cells with low glucose treatment. Decreased 5' AMP-activated
      protein kinase (AMPK) and increased mTOR activity was investigated in miR-451
      redistributed T cells and the Th17 polarized differentiation of these T cells
      were also increased. Exosome miR-451 derived from tumor tissues can serve as an
      indicator for poor prognosis and redistribution of miR-451 from cancer cells to
      infiltrated T cells in low glucose treatment can enhance Th17 differentiation by
      enhancing mTOR activity.

PMID- 29059498
TI  - Respiratory reflex generated by movement of the arms.

PMID- 29059499
TI  - Oligomeric proanthocyanidins protect myocardium by mitigating left ventricular
      remodeling in isoproterenol-induced postmyocardial infarction.
AB  - Extracellular matrix (ECM) remodeling is a major pathophysiological process
      during post-myocardial infarction (MI). The activation, differentiation, and
      proliferation of cardiac fibroblasts to myofibroblasts regulate the expression of
      ECM proteins. The signaling by bone morphogenetic protein (BMP-4), an
      extracellular ligand of the TGF-beta family, has recently been identified as an
      essential pathway in regulating cardiovascular dysfunctions including myocardial
      fibrosis. Oligomeric proanthocyanidins (OPC) are well known for their
      cardioprotective activity. The primary aim of the study was to investigate BMP-4
      mediated ECM turnover in cardiac fibrosis during isoproterenol-induced post-MI
      and its downregulation by OPC. Myocardial injury was evaluated by assaying serum
      markers LDH and CK. Oxidative stress and the enzymatic and nonenzymatic
      antioxidant levels were assessed to support the cardioprotective nature of OPC.
      The total collagen level was analyzed by measuring hydroxyproline levels. The ISO
      induced group showed a significant decrease in the levels of antioxidants due to
      severe oxidative stress and increased expression of BMP-4 which reflects the
      increased expression of MMP 2 and 9 with a concomitant increase and deposition of
      fibrillary collagens type I and III responsible for the fibrotic scar formation
      as evidenced in the histological analysis.BMP-4 activation, thus, is strongly
      associated with cardiac fibrosis which was downregulated upon OPC
      supplementation. This study provides an evidence supporting the antifibrotic
      effect of OPC via regulation of BMP-4-mediated ECM turnover and also
      substantiates the remarkable antioxidant efficacy of OPC against isoproterenol
      induced severe oxidative stress and subsequent post-MI cardiac fibrosis.

PMID- 29059497
TI  - A recessive ataxia diagnosis algorithm for the next generation sequencing era.
AB  - OBJECTIVE: Differential diagnosis of autosomal recessive cerebellar ataxias can
      be challenging. A ranking algorithm named RADIAL that predicts the molecular
      diagnosis based on the clinical phenotype of a patient has been developed to
      guide genetic testing and to align genetic findings with the clinical context.
      METHODS: An algorithm that follows clinical practice, including patient history,
      clinical, magnetic resonance imaging, electromyography, and biomarker features,
      was developed following a review of the literature on 67 autosomal recessive
      cerebellar ataxias and personal clinical experience. Frequency and specificity of
      each feature were defined for each autosomal recessive cerebellar ataxia, and
      corresponding prediction scores were assigned. Clinical and paraclinical features
      of patients are entered into the algorithm, and a patient's total score for each
      autosomal recessive cerebellar ataxia is calculated, producing a ranking of
      possible diagnoses. Sensitivity and specificity of the algorithm were assessed by
      blinded analysis of a multinational cohort of 834 patients with molecularly
      confirmed autosomal recessive cerebellar ataxia. The performance of the algorithm
      was assessed versus a blinded panel of autosomal recessive cerebellar ataxia
      experts. RESULTS: The correct diagnosis was ranked within the top 3 highest
      scoring diagnoses at a sensitivity and specificity of >90% for 84% and 91% of the
      evaluated genes, respectively. Mean sensitivity and specificity of the top 3
      highest-scoring diagnoses were 92% and 95%, respectively. The algorithm
      outperformed the panel of ataxia experts (p = 0.001). INTERPRETATION: Our
      algorithm is highly sensitive and specific, accurately predicting the underlying
      molecular diagnoses of autosomal recessive cerebellar ataxias, thereby guiding
      targeted sequencing or facilitating interpretation of next-generation sequencing
      data. Ann Neurol 2017;82:892-899.

PMID- 29059501
TI  - Head-to-Tail Cyclic Peptide Inhibitors of the Interaction between Human von
      Willebrand Factor and Collagen.
AB  - The development of peptide-based therapeutics is on the rise, with macrocyclic
      compounds providing the added stability and drug-like characteristics sought
      after. Currently, therapies and preventatives for pathogenic thrombosis target
      platelet interactions at the site of the clot and have many complications. Herein
      we describe novel cyclic peptides as moderate inhibitors of the protein-protein
      interaction between von Willebrand factor (vWF) and collagen that initiates blood
      clot formation. We based our designs on two known disulfide-containing, peptide
      based inhibitors of the vWF-collagen interaction. Replacing the disulfide with a
      head-to-tail cyclization strategy confers remarkable stability to the peptides
      when treated with a panel of proteases. Our peptides also showed moderate
      activity in our developed fluorescently linked immunosorbent assay (FLISA),
      similar to the most active disulfide-containing peptide. These peptides provide a
      springboard for future advances in exceptionally stable, active cyclic peptides
      as drugs.

PMID- 29059500
TI  - Role of extracytoplasmic function sigma factor PG1660 (RpoE) in the oxidative
      stress resistance regulatory network of Porphyromonas gingivalis.
AB  - In Porphyromonas gingivalis, the protein PG1660, composed of 174 amino acids, is
      annotated as an extracytoplasmic function (ECF) sigma factor (RpoE homologue
      sigma24). Because PG1660 can modulate several virulence factors and responds to
      environmental signals in P. gingivalis, its genetic properties were evaluated.
      PG1660 is co-transcribed with its downstream gene PG1659, and the transcription
      start site was identified as adenine residue 54-nucleotides upstream of the ATG
      translation start codon. In addition to binding its own promoter, using the
      purified rPG1660 and RNAP core enzyme from Escherichia coli with the PG1660
      promoter DNA as template, the function of PG1660 as a sigma factor was
      demonstrated in an in vitro transcription assay. Transcriptome analyses of a P.
      gingivalis PG1660-defective isogenic mutant revealed that under oxidative stress
      conditions 176 genes including genes involved in secondary metabolism were
      downregulated more than two-fold compared with the parental strain. The rPG1660
      protein also showed the ability to bind to the promoters of the highly
      downregulated genes in the PG1660-deficient mutant. As the ECF sigma factor
      PG0162 has a 29% identity with PG1660 and can modulate its expression, the cross
      talk between their regulatory networks was explored. The expression profile of
      the PG0162PG1660-deficient mutant (P. gingivalis FLL356) revealed that the type
      IX secretion system genes and several virulence genes were downregulated under
      hydrogen peroxide stress conditions. Taken together, we have confirmed that
      PG1660 can function as a sigma factor, and plays an important regulatory role in
      the oxidative stress and virulence regulatory network of P. gingivalis.

PMID- 29059502
TI  - Effects of the Protonation State of Titratable Residues and the Presence of Water
      Molecules on Nocodazole Binding to beta-Tubulin.
AB  - Regulation of microtubule assembly by antimitotic agents is a potential
      therapeutic strategy for the treatment of cancer, parasite infections, and
      neurodegenerative diseases. One of these agents is nocodazole (NZ), which
      inhibits microtubule polymerization by binding to beta-tubulin. NZ was recently
      co-crystallized in Gallus gallus tubulin, providing new information about the
      features of interaction for ligand recognition and stability. In this work, we
      used state-of-the-art computational approaches to evaluate the protonation
      effects of titratable residues and the presence of water molecules in the binding
      of NZ. Analysis of protonation states showed that residue E198 has the largest
      modification in its pKa value. The resulting E198 pKa value, calculated with pH
      REMD methodology (pKa =6.21), was higher than the isolated E amino acid (pKa
      =4.25), thus being more likely to be found in its protonated state at the binding
      site. Moreover, we identified an interaction between a water molecule and C239
      and G235 as essential for NZ binding. Our results suggest that the protonation
      state of E198 and the structural water molecules play key roles in the binding of
      NZ to beta-tubulin.

PMID- 29059504
TI  - Intersection of Proteomics and Genomics to "Solve the Unsolved" in Rare Disorders
      such as Neurodegenerative and Neuromuscular Diseases.
AB  - Despite recent rapid advances in sequencing technologies, a significant
      proportion of patients with rare genetic disorders do not receive a genetic
      diagnosis after exhaustive testing, and even fewer have a potential therapeutic
      target identified. Taking rare neuromuscular and neurodegenerative disorders as a
      paradigm that can be extended to other rare Mendelian disorders, this viewpoint
      explores the opportunities that are brought about by the integration of genomics
      and proteomics, as well as the limitations and remaining challenges of this newly
      emerging field of proteogenomics. The relevance of combining proteomic findings
      with genetic results for diagnosis and gene discovery is illustrated,
      highlighting the insights the combined analysis provides into the underlying
      biology and aetiology as well as the limitations of the experimental techniques.
      A final discussion focuses on the importance of mechanisms to enable the sharing,
      reuse, and analysis of source experimental data and describes some of the
      international initiatives that are making progress in this area.

PMID- 29059505
TI  - Scandium-Catalyzed Self-Assisted Polar Co-monomer Enchainment in Ethylene
      Polymerization.
AB  - Direct coordinative copolymerization of ethylene with functionalized co-monomers
      is a long-sought-after approach to introducing polyolefin functionality. However,
      functional-group Lewis basicity typically depresses catalytic activity and co
      monomer incorporation. Finding alternatives to intensively studied group 4 d0 and
      late-transition-metal catalysts is crucial to addressing this long-standing
      challenge. Shown herein is that mono- and binuclear organoscandium complexes with
      a borate cocatalyst are active for ethylene + amino olefin [AO; H2 C=CH(CH2 )n
      NR2 ] copolymerizations in the absence of a Lewis-acidic masking reagent. Both
      activity (up to 4.2*102  kg mol-1 ?h-1>  atm-1> ) and AO incorporation (up to 12
      % at 0.2 m [AO]) are appreciable. Linker-length-dependent (n) AO incorporation
      and mechanistic probes support an unusual functional-group-assisted enchainment
      mechanism. Furthermore, the binuclear catalysts exhibit enhanced AO tolerance and
      enhanced long chain AO incorporation.

PMID- 29059506
TI  - The Spotted Gar: Genomic Journeys into a Lost World.

PMID- 29059503
TI  - Optimization of Substrate-Analogue Furin Inhibitors.
AB  - The proprotein convertase furin is a potential target for drug design, especially
      for the inhibition of furin-dependent virus replication. All effective synthetic
      furin inhibitors identified thus far are multibasic compounds; the highest
      potency was found for our previously developed inhibitor 4
      (guanidinomethyl)phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148). An
      initial study in mice revealed a narrow therapeutic range for this tetrabasic
      compound, while significantly reduced toxicity was observed for some tribasic
      analogues. This suggests that the toxicity depends at least to some extent on the
      overall multibasic character of this inhibitor. Therefore, in a first approach,
      the C-terminal benzamidine of MI-1148 was replaced by less basic P1 residues.
      Despite decreased potency, a few compounds still inhibit furin in the low
      nanomolar range, but display negligible efficacy in cells. In a second approach,
      the P2 arginine was replaced by lysine; compared to MI-1148, this furin inhibitor
      has slightly decreased potency, but exhibits similar antiviral activity against
      West Nile and Dengue virus in cell culture and decreased toxicity in mice. These
      results provide a promising starting point for the development of efficacious and
      well-tolerated furin inhibitors.

PMID- 29059507
TI  - The non-visual opsins: eighteen in the ancestor of vertebrates, astonishing
      increase in ray-finned fish, and loss in amniotes.
AB  - Non-visual opsins were discovered in the early 1990s. These genes play roles in
      circadian rhythm in mammals, seasonal reproduction in birds, light avoidance in
      amphibian larvae, and neural development in fish. However, the interpretation of
      such studies and the success of future work are compromised by the fact that non
      visual opsin repertoires have not been properly characterized in any of these
      lineages. Here, we show that non-visual opsins from tetrapods and ray-finned fish
      are distributed among 18 monophyletic subfamilies. An amphibian sequence occurs
      in every subfamily, whereas mammalian orthologs occur in only seven. Species in
      the major ray-finned fish lineages, Holostei, Osteoglossomorpha, Otomorpha,
      Protacanthopterygii, and Neoteleostei, have large numbers of non-visual opsins
      (22-32 genes) as a result of gene duplication events including, but not limited
      to, the teleost genome duplication (TGD). In contrast to visual opsins, where
      lineage-specific duplication is common, the ray-finned fish non-visual opsin
      repertoire appears to have stabilized shortly after the TGD event and
      consequently even distantly related species have repertoires of similar size and
      composition. Most non-visual opsins have been named without the benefit of a
      phylogenetic perspective and, accordingly, major revisions are proposed.

PMID- 29059508
TI  - Large-Scale, Long-Range-Ordered Patterning of Nanocrystals via Capillary-Bridge
      Manipulation.
AB  - Deterministic assembly of nanoparticles with programmable patterns is a core
      opportunity for property-by-design fabrication and large-scale integration of
      functional materials and devices. The wet-chemical-synthesized colloidal
      nanocrystals are compatible with solution assembly techniques, thus possessing
      advantages of high efficiency, low cost, and large scale. However, conventional
      solution process suffers from tradeoffs between spatial precision and long-range
      order of nanocrystal assembly arising from the uncontrollable dewetting dynamics
      and fluid flow. Here, a capillary-bridge manipulation method is demonstrated for
      directing the dewetting of nanocrystal inks and deterministically patterning long
      range-ordered superlattice structures. This is achieved by employing micropillars
      with programmable size, arrangement, and shape, which permits deterministic
      manipulation of geometry, position, and dewetting dynamics of capillary bridges.
      Various superlattice structures, including one-dimensional (1D), circle, square,
      pentagon, hexagon, pentagram, cross arrays, are fabricated. Compared to the
      glassy thin films, long-range-ordered superlattice arrays exhibit improved
      ferroelectric polarization. Coassembly of nanocrystal superlattice and organic
      functional molecule is further demonstrated. Through introducing azobenzene into
      superlattice arrays, a switchable ferroelectric polarization is realized, which
      is triggered by order-disorder transition of nanocrystal stacking in reversible
      isomerization process of azobenzene. This method offers a platform for patterning
      nanocrystal superlattices and fabricating microdevices with functionalities for
      multiferroics, electronics, and photonics.

PMID- 29059509
TI  - Gene therapy for neuropathic pain induced by spared nerve injury with naked
      plasmid encoding hepatocyte growth factor.
AB  - BACKGROUND: Neuropathic pain (NP) is a refractory disease in the clinic with a
      tremendous impact on the quality of life of patients. Gene therapy is a potential
      strategy for the management of NP. In the present study, we examined the
      analgesic effect and mechanism of hepatocyte growth factor (HGF) in vitro and in
      vivo. METHODS: We examined the proinflammatroy gene changes in lipopolysaccharide
      (LPS)-induced microglia BV2 cells with a quantitative real-time polymerase chain
      reaction of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha and
      inducible nitric oxide synthase (iNOS). Mechanical stimulation tests were
      performed five times at 5-min intervals to assess pain thresholds using Von Frey
      Hair in mice following spared nerve injury (SNI). The glial cell activation of
      spinal cord was examined by western blotting. Statistical significance was
      determined by a Tukey's test and a paired t-test. RESULTS: We found that
      recombinant human HGF protein suppressed LPS-induced BV2 cell activation in
      vitro, marked by the down-regulation of IL-1beta, IL-6, TNF-alpha and iNOS
      expression, as well as decrease of nitric oxide production. Moreover, intrathecal
      injection of naked plasmid encoding HGF gene (pUDK-HGF) significantly attenuated
      SNI-induced pain behaviors in mice by direct inhibition of spinal cord microglia
      and astrocyte activation. CONCLUSIONS: The results of the present study indicate
      that pUDK-HGF can reduce cytotoxicity products released from activated glial
      cells, which may provide a promising therapeutic strategy for treating NP.

PMID- 29059510
TI  - Glucose response to exercise in the post-prandial period is independent of
      exercise intensity.
AB  - This study investigated the acute glucose response to low-intensity, moderate
      intensity, and high-intensity interval exercise compared to no-exercise in
      healthy insufficiently active males using a four-arm, randomized, crossover
      design. Ten males (age: 37.3 +/- 7.3 years, BMI: 29.3 +/- 6.5 kg.m-2 ) completed
      four 30-minute interventions at weekly intervals comprising low-intensity
      exercise (LIE) at ~35% VO2 R, moderate-intensity exercise (MIE) at ~50% VO2 R,
      high-intensity interval exercise (HIIE) at ~80% VO2 R, and a no-exercise control.
      Participants performed cycle ergometer exercise 30 minutes after finishing
      breakfast. Glucose response was assessed using a continuous glucose monitor under
      free-living conditions with dietary intake replicated. A significant effect for
      intensity on energy expenditure was identified (P < .001) with similar energy
      cost in MIE (mean +/- SD: 869 +/- 148 kJ) and HIIE (806 +/- 145 kJ), which were
      both greater than LIE (633 +/- 129 kJ). The pattern of glucose response between
      the interventions over time was different (P = .02). Glucose was lower 25 minutes
      into each of the HIIE, MIE and LIE trials respectively (mean difference +/- SD: 
      0.7 +/- 1.1; -0.9 +/- 1.1; -0.6 +/- 0.9 mmol.L-1 ; P < .05) than in the no
      exercise trial. Glucose response was not different between exercise intensities
      (P > .05). Twenty-four-hour AUC was not affected by exercise intensity (P = .75).
      There was a significant effect for exercise enjoyment (P = .02), with LIE (69 +/-
      4) preferred less than HIIE (mean +/- SD: 84 +/- 14; P = .02), MIE (73 +/- 5; P =
      .03), and no-exercise (75 +/- 4; P = .03). Exercise at any intensity 30 minutes
      after a meal affects glycemic regulation equally in insufficiently active males.
      Moderate to vigorous exercise intensities were preferred, and therefore, the
      exercise guidelines appear appropriate for the prevention of cardiometabolic
      disease.

PMID- 29059511
TI  - New biologics in psoriasis - progress and problems.

PMID- 29059512
TI  - Corrigendum.

PMID- 29059513
TI  - The increasing incidence of frontal fibrosing alopecia. In search of triggering
      factors.

PMID- 29059514
TI  - Organic Solvent-Free Fabrication of Durable and Multifunctional Superhydrophobic
      Paper from Waterborne Fluorinated Cellulose Nanofiber Building Blocks.
AB  - In view of a great demand for paper-based technologies, nonwettable fibrous
      substrates with excellent durability have drawn much attention in recent years.
      In this context, the use of cellulose nanofibers (CNFs), the smallest unit of
      cellulosic substrates (5-20 nm wide and 500 nm to several microns in length), to
      design waterproof paper can be an economical and smart approach. In this study,
      an eco-friendly and facile methodology to develop a multifunctional waterproof
      paper via the fabrication of fluoroalkyl functionalized CNFs in the aqueous
      medium is presented. This strategy avoids the need for organic solvents, thereby
      minimizing cost as well as reducing safety and environmental concerns. Besides,
      it widens the applicability of such materials as nanocellulose-based aqueous
      coatings on hard and soft substrates including paper, in large areas. Water
      droplets showed a contact angle of 160 degrees  (+/-2 degrees ) over these
      surfaces and rolled off easily. While native CNFs are extremely hydrophilic and
      can be dispersed in water easily, these waterborne fluorinated CNFs allow the
      fabrication of a superhydrophobic film that does not redisperse upon submersion
      in water. Incorporated chemical functionalities provide excellent durability
      toward mechanochemical damages of relevance to daily use such as knife scratch,
      sand abrasion, spillage of organic solvents, etc. Mechanical flexibility of the
      chemically modified CNF composed paper remains intact despite its enhanced
      mechanical strength, without additives. Superhydrophobicity induced excellent
      microbial resistance of the waterproof paper which expands its utility in various
      paper-based technologies. This includes waterproof electronics, currency, books,
      etc., where the integrity of the fibers, as demonstrated here, is a much-needed
      criterion.

PMID- 29059515
TI  - Effectiveness of Germination on Protein Hydrolysis as a Way To Reduce Adverse
      Reactions to Wheat.
AB  - In this work, the aim is to study the effectiveness of germination on wheat
      protein degradation, with a specific focus on proteins involved in adverse
      reactions to wheat. The effects of 8 days of germination at 25  degrees C on the
      chemical composition and the protein profile were determined. Germination did not
      have a significant effect on starch, protein, lipid, and ash contents. General
      protein profile, as indicated by SDS-PAGE analysis, revealed that germination
      induced a relevant degradation in protein fraction. After in vitro
      gastrointestinal digestion, gluten peptides involved in celiac disease (CD) were
      identified and quantified using UPLC/ESI-MS technique. Also, CM3 protein,
      involved in baker's asthma and intestinal inflammation, was quantified by
      measuring a marker peptide. Statistical analysis underlined that germination and
      genotype had significant impact on the amount of both components. Regarding
      gluten peptides related to CD, germination enabled an average reduction of 47% in
      peptides eliciting adaptive immune response and 46% in peptides eliciting innate
      immune response. CM3 protein showed also a high average reduction (56%). Thus,
      this study suggests that germination might be a good bioalternative to provide a
      low "impact" raw ingredient for special wheat-based foodstuffs.

PMID- 29059516
TI  - Electrospun Micropatterned Nanocomposites Incorporated with Cu2S Nanoflowers for
      Skin Tumor Therapy and Wound Healing.
AB  - Surgical excision of skin cancers can hardly remove the tumor tissues completely
      and simultaneously result in cutaneous defects. To avoid tumor recurrence and
      heal the tumor-induced wounds, we designed a tissue engineering membrane
      possessing bifunctions of tumor therapy and skin tissue regeneration. The
      micropatterned nanocomposite membrane was successfully fabricated by
      incorporating Cu2S nanoflowers into biopolymer fibers via a modified
      electrospinning method. With uniformly embedded Cu2S nanoparticles, the membranes
      exhibited excellent and controllable photothermal performance under near-infrared
      irradiation, which resulted in high mortality (>90%) of skin tumor cells and
      effectively inhibited tumor growth in mice. Moreover, the membranes supported the
      adhesion, proliferation, and migration of skin cells as well as significantly
      stimulated angiogenesis and healed full-thickness skin defects in vivo. This
      proof-of-concept study offers a facile and reliable strategy for localized skin
      tumor therapy and tissue regeneration using bifunctional tissue engineering
      biomaterials, showing great promise for tumor-induced wound healing applications.

PMID- 29059517
TI  - Preparation and Characterization of Hypoglycemic Nanoparticles for Oral Insulin
      Delivery.
AB  - Polymeric nanoparticles have been widely investigated as insulin delivery systems
      for oral administration. However, the toxic nature of many artificial polymers
      hampers their effective application, creating a demand for the further
      exploration of alternative natural polymers. In addition, ethnobotanical research
      has reported that over 800 plant species have a hypoglycemic function, some of
      which are polymers. For the advantages of both areas to be combined, the aim of
      this work was to choose an organic hypoglycemic polymer and prepare it into an
      insulin carrier to build a dual-functional oral insulin delivery system. We found
      that the insulin loading rate, release mode, thermostability, and both in vitro
      and in vivo absorption and efficacy varied with the different modifications of
      polygalacturonic acid (PGLA) nanoparticulate backbones. By in vivo pharmaceutical
      testing and constantly monitoring the symptoms of type 1 diabetic (T1D) rats, we
      ascertained the hypoglycemic function of the nanoparticles and showed that
      overall diabetic symptoms were ameliorated after the long-term daily
      administration of nanoparticles with no significant damage to organ structure or
      cell viability.

PMID- 29059518
TI  - Nature of Active Sites and Surface Intermediates during SCR of NO with NH3 by
      Supported V2O5--WO3/TiO2 Catalysts.
AB  - Time-resolved in situ IR was performed during selective catalytic reduction of NO
      with NH3 on supported V2O5-WO3/TiO2 catalysts to examine the distribution and
      reactivity of surface ammonia species on Lewis and Bronsted acid sites. While
      both species were found to participate in the SCR reaction, their relative
      population depends on the coverage of the surface vanadia and tungsta sites,
      temperature, and moisture. Although the more abundant surface NH4+,ads
      intermediates dominate the overall SCR reaction, especially for hydrothermally
      aged catalysts, the minority surface NH3,ads intermediates exhibit a higher
      specific SCR activity (TOF). The current study serves to resolve the long
      standing controversy about the active sites for SCR of NO with NH3 by supported
      V2O5-WO3/TiO2 catalysts.

PMID- 29059519
TI  - Manipulation of Contents of Nitrate, Phenolic Acids, Chlorophylls, and
      Carotenoids in Lettuce (Lactuca sativa L.) via Contrasting Responses to Nitrogen
      Fertilizer When Grown in a Controlled Environment.
AB  - This study aimed to use different nitrogen fertilizer regimes to produce
      Butterhead lettuce with such large differences in nitrate content that they could
      be used as treatment and placebo to study the effect of inorganic nitrate on
      human health. Plants were grown under controlled conditions at 27/23  degrees C
      day/night with a relatively low photosynthetically active radiation (PAR) of 150
      MUmol m-2 s-1 for 14 h day-1 and nitrogen supplies ranging from 26 to 154 ppm of
      N as ammonium nitrate in the fertigation solution. This resulted in contrasting
      high (~1078 mg nitrate 100 g-1 FW) or low (~6 mg 100 g-1) nitrate contents in the
      leaves. Contents of carotenoids and chlorophylls in fresh weight did not differ
      significantly between the highest and the lowest N-supply levels. However,
      increased nitrogen supply reduced contents of phenolic compounds from 154 to 22
      mg 100 g-1 FW, dry matter content from 8.9% to 4.6%, and fresh weight per plant
      from 108.52 to 47.57 g/plant FW (all P < 0.001). Thus, while fertilizer
      treatments can provide lettuce with substantially different nitrate contents,
      maintaining similar pigment contents (color), they also strongly influence the
      contents of phenolic acids and flavones.

PMID- 29059520
TI  - Thermodynamic Description of Synergy in Solvent Extraction: II Thermodynamic
      Balance of Driving Forces Implied in Synergistic Extraction.
AB  - In the second part of this study, we analyze the free energy of transfer in the
      case of synergistic solvent extraction. This free energy of the transfer of an
      ion in dynamic equilibrium between two coexisting phases is decomposed into four
      driving forces combining long-range interactions with the classical complexation
      free energy associated with the nearest neighbors. We demonstrate how the
      organometallic complexation is counterbalanced by the cost in free energy related
      to structural change on the colloidal scale in the solvent phase. These molecular
      forces of synergistic extraction are driven not only by the entropic term
      associated with the tight packing of electrolytes in the solvent and by the free
      energy cost of coextracting water toward the hydrophilic core of the reverse
      aggregates present but also by the entropic costs in the formation of the reverse
      aggregate and by the interfacial bending energy of the extractant molecules
      packed around the extracted species. Considering the sum of the terms, we can
      rationalize the synergy observed, which cannot be explained by classical
      extraction modeling. We show an industrial synergistic mixture combining an amide
      and a phosphate complexing site, where the most efficient/selective mixture is
      observed for a minimal bending energy and maximal complexation energy.

PMID- 29059521
TI  - Synthesis of (+)-Pancratistatins via Catalytic Desymmetrization of Benzene.
AB  - A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from
      benzene using an enantioselective, dearomative carboamination strategy has been
      achieved. This approach, in combination with the judicious choice of subsequent
      olefin-type difunctionalization reactions, permits rapid and controlled access to
      a hexasubstituted core. Finally, minimal use of intermediary steps as well as
      direct, late stage C-7 hydroxylation provides both natural products in six and
      seven operations.

PMID- 29059522
TI  - Impact of Microplastic Beads and Fibers on Waterflea (Ceriodaphnia dubia)
      Survival, Growth, and Reproduction: Implications of Single and Mixture Exposures.
AB  - There is limited knowledge regarding the adverse effects of wastewater-derived
      microplastics, particularly fibers, on aquatic biota. In this study, we examined
      the acute (48 h) and chronic (8 d) effects of microplastic polyester fibers and
      polyethylene (PE) beads on freshwater zooplankton Ceriodaphnia dubia. We also
      assessed the acute response of C. dubia to a binary mixture of microplastic beads
      and fibers for the first time. Acute exposure to fibers and PE beads both showed
      a dose-dependent effect on survival. An equitoxic binary mixture of beads and
      fibers resulted in a toxic unit of 1.85 indicating less than additive effects.
      Chronic exposure to lower concentrations did not significantly affect survival of
      C. dubia, but a dose-dependent effect on growth and reproduction was observed.
      Fibers showed greater adverse effects than PE beads. While ingestion of fibers
      was not observed, scanning electron microscopy showed carapace and antenna
      deformities after exposure to fibers, with no deformities observed after exposure
      to PE beads. While much of the current research has focused on microplastic
      beads, our study shows that microplastic fibers pose a greater risk to C. dubia,
      with reduced reproductive output observed at concentrations within an order of
      magnitude of reported environmental levels.

PMID- 29059523
TI  - Conversion of Alcohols to Phosphorothiolates Using a Thioiminium Salt as Coupling
      Agent.
AB  - We report a method for the direct and rapid conversion of primary and secondary
      alcohols to the corresponding phosphorothiolates in yields ranging from 64% to
      97%, using as a coupling agent the iminium salt prepared from N,N
      dimethylthioformamide and Meerwein's salt. Selective reaction of primary alcohols
      in the presence of secondary alcohols is possible. The reaction of secondary
      alcohols proceeds stereospecifically with inversion of configuration.

PMID- 29059524
TI  - Computing Prediction and Functional Analysis of Prokaryotic Propionylation.
AB  - Identification and systematic analysis of candidates for protein propionylation
      are crucial steps for understanding its molecular mechanisms and biological
      functions. Although several proteome-scale methods have been performed to
      delineate potential propionylated proteins, the majority of lysine-propionylated
      substrates and their role in pathological physiology still remain largely
      unknown. By gathering various databases and literatures, experimental prokaryotic
      propionylation data were collated to be trained in a support vector machine with
      various features via a three-step feature selection method. A novel online tool
      for seeking potential lysine-propionylated sites (PropSeek) (
      http://bioinfo.ncu.edu.cn/PropSeek.aspx ) was built. Independent test results of
      leave-one-out and n-fold cross-validation were similar to each other, showing
      that PropSeek is a stable and robust predictor with satisfying performance.
      Meanwhile, analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes
      pathways, and protein-protein interactions implied a potential role of
      prokaryotic propionylation in protein synthesis and metabolism.

PMID- 29059525
TI  - Dynamic Histogram Analysis To Determine Free Energies and Rates from Biased
      Simulations.
AB  - We present an algorithm to calculate free energies and rates from molecular
      simulations on biased potential energy surfaces. As input, it uses the
      accumulated times spent in each state or bin of a histogram and counts of
      transitions between them. Optimal unbiased equilibrium free energies for each of
      the states/bins are then obtained by maximizing the likelihood of a master
      equation (i.e., first-order kinetic rate model). The resulting free energies also
      determine the optimal rate coefficients for transitions between the states or
      bins on the biased potentials. Unbiased rates can be estimated, e.g., by imposing
      a linear free energy condition in the likelihood maximization. The resulting
      "dynamic histogram analysis method extended to detailed balance" (DHAMed) builds
      on the DHAM method. It is also closely related to the transition-based
      reweighting analysis method (TRAM) and the discrete TRAM (dTRAM). However, in the
      continuous-time formulation of DHAMed, the detailed balance constraints are more
      easily accounted for, resulting in compact expressions amenable to efficient
      numerical treatment. DHAMed produces accurate free energies in cases where the
      common weighted-histogram analysis method (WHAM) for umbrella sampling fails
      because of slow dynamics within the windows. Even in the limit of completely
      uncorrelated data, where WHAM is optimal in the maximum-likelihood sense, DHAMed
      results are nearly indistinguishable. We illustrate DHAMed with applications to
      ion channel conduction, RNA duplex formation, alpha-helix folding, and rate
      calculations from accelerated molecular dynamics. DHAMed can also be used to
      construct Markov state models from biased or replica-exchange molecular dynamics
      simulations. By using binless WHAM formulated as a numerical minimization
      problem, the bias factors for the individual states can be determined efficiently
      in a preprocessing step and, if needed, optimized globally afterward.

PMID- 29059526
TI  - p-Sulfonatocalix[6]arene-dodecyltrimethylammonium Supramolecular Amphiphilic
      System: Relationship between Calixarene and Micelle Concentration.
AB  - In this work, the formation of supramolecular mixed micelles from a
      hexamethylated p-sulfonatocalix[6]arene (SC6HM) derivative and a conventional
      cationic surfactant (dodecyltrimethylammonium bromide, C12TAB) was investigated
      by surface tension and using pyrene as a micropolarity fluorescent probe to gain
      insights into the role of the calixarene concentration on the aggregation
      behavior. The formation of micelles at a concentration well below the critical
      micelle concentration of pure surfactant was observed in the presence of very low
      concentrations of SC6HM (below the micromolar range). Interestingly, the critical
      micelle concentration of the mixed system was shown to be rather insensitive to
      the concentration of SC6HM. On the other hand, the concentration of mixed
      micellar aggregates was demonstrated to be highly dependent on the macrocycle
      concentration and less dependent on the C12TAB concentration in the range between
      the critical micelle concentrations of the mixed systems and pure surfactant.

PMID- 29059527
TI  - Control of the Porous Structure of Polystyrene Particles Obtained by Nonsolvent
      Induced Phase Separation.
AB  - Porous polystyrene microspheres were produced by a process of nonsolvent induced
      phase separation (NIPS) from ternary polymer-solvent-nonsolvent (polystyrene
      toluene-ethanol) systems and characterized by scanning electron microscopy (SEM)
      and small-angle X-ray scattering (SAXS) techniques. This study provides evidence
      for a link between the structural morphology of the porous polystyrene particles
      and the polystyrene concentration in the initial solutions. A reciprocal
      relationship between pore diameter and polymer concentration was observed for the
      systems with the polymer amount below the critical chain overlap concentration,
      C*. Above C*, this relationship breaks down. The reciprocal relationship between
      porosity and polymer concentration can be used to facilitate the fine control of
      the void size. We demonstrate that the observed reciprocal relationship between
      pore diameter and polymer concentration correlates well with the relative amount
      of nonsolvent present in the system at the onset of the phase separation process.
      The pore size can be reduced and, consequently, the pore surface area can be
      increased either by reducing the polymer concentration in the initial solution or
      by decreasing the polymer molecular weight in the sample composition.

PMID- 29059528
TI  - Glycosylated Reversible Addition-Fragmentation Chain Transfer Polymers with
      Varying Polyethylene Glycol Linkers Produce Different Short Interfering RNA
      Uptake, Gene Silencing, and Toxicity Profiles.
AB  - Achieving efficient and targeted delivery of short interfering (siRNA) is an
      important research challenge to overcome to render highly promising siRNA
      therapies clinically successful. Challenges exist in designing synthetic carriers
      for these RNAi constructs that provide protection against serum degradation,
      extended blood retention times, effective cellular uptake through a variety of
      uptake mechanisms, endosomal escape, and efficient cargo release. These
      challenges have resulted in a significant body of research and led to many
      important findings about the chemical composition and structural layout of the
      delivery vector for optimal gene silencing. The challenge of targeted delivery
      vectors remains, and strategies to take advantage of nature's self-selective
      cellular uptake mechanisms for specific organ cells, such as the liver, have
      enabled researchers to step closer to achieving this goal. In this work, we
      report the design, synthesis, and biological evaluation of a novel polymeric
      delivery vector incorporating galactose moieties to target hepatic cells through
      clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation
      into the density of carbohydrate functionality and its distance from the polymer
      backbone is conducted using reversible addition-fragmentation chain transfer
      polymerization and postpolymerization modification.

PMID- 29059529
TI  - Self-Assembled Polypeptide Nanogels with Enzymatically Transformable Surface as a
      Small Interfering RNA Delivery Platform.
AB  - Nanometer-size gel particles, or nanogels, have potential for delivering
      therapeutic macromolecules. A cationic surface promotes cellular internalization
      of nanogels, but undesired electrostatic interactions, such as with blood
      components, cause instability and toxicities. Poly(ethylene glycol) coating has
      been used to shield charges, but this decreases delivery efficiency. Technical
      difficulties in synthesis and controlling molecular weights make it unfeasible
      to, instead, coat with biodegradable polymers. Our proposed solution is
      cationized nanogels enzymatically functionalized with branched polysaccharide
      chains, forming a shell to shield charges and increase stability. Biodegradation
      of the polysaccharides by an endogenous enzyme would then expose the cationic
      charges, allowing cellular internalization and cargo delivery. We tested this
      concept, preparing maltopentaose functionalized cholesteryl poly(l-lysine)
      nanogel and using tandem enzymatic polymerization with glycogen phosphorylase and
      glycogen branching enzyme, to add branched amylose moieties, forming a CbAmyPL
      nanogel. We characterized CbAmyPL nanogels and investigated their suitability as
      small interfering RNA (siRNA) carriers in murine renal carcinoma (Renca) cells.
      The nanogels had neutral zeta potential values that became positive after
      degradation by alpha-amylase. Foster resonance energy transfer demonstrated that
      the nanogels formed stable complexes with siRNA, even in the presence of bovine
      serum albumin and after alpha-amylase exposure. The nanogels, with or without
      alpha-amylase, were not cytotoxic. Complexes of CbAmyPL with siRNA against
      vascular endothelial growth factor (VEGF), when incubated alone with Renca cells
      decreased VEGF mRNA levels by only 20%. With alpha-amylase added, however, VEGF
      mRNA knockdown by the siRNA/nanogels complexes was 50%. Our findings strongly
      supported the hypothesis that enzyme-responsive nanogels are promising as a
      therapeutic siRNA delivery platform.

PMID- 29059530
TI  - Enhanced Antimicrobial Efficacy of Bimetallic Porous CuO Microspheres Decorated
      with Ag Nanoparticles.
AB  - The antimicrobial action of porous CuO microspheres (MUCuO), Ag nanoparticles
      (nAg), and bimetallic porous CuO microspheres decorated with Ag nanoparticles
      (MUCuO/nAg) was evaluated against surrogate microorganisms representative of
      pathogens commonly implicated in foodborne and healthcare-associated human
      infections. This work addressed the Gram-negative bacteria E. coli (Escherichia
      coli O157:H7-GFP B6-914), Salmonella (Salmonella enterica serovar enteritidis
      phage-type PT21), and the Gram-positive bacteria Listeria (Listeria innocua), as
      well as environmental microorganisms derived from local river water. Compared to
      particles composed only of CuO or Ag, the bimetallic porous MUCuO/nAg particle
      exhibits enhanced antimicrobial efficacy. The antimicrobial action of bimetallic
      porous MUCuO/nAg particles is dose-dependent, with 50 MUg/mL particle
      concentration completely inhibiting the growth of both the Gram-negative
      (Salmonella) and the Gram-positive (Listeria) bacteria after 6 h. To assess the
      mechanism of antimicrobial action, the changes in surface morphologies of
      bacteria treated with the particles were observed using scanning electron
      microscopy. In the case of the Gram-negative bacteria, the bacterial cell
      membrane is damaged, likely due to the release of metal ions from the particles;
      however, particle-induced cell membrane damage is not observed for Gram-positive
      bacteria. Collectively, results from this work shed further light on possible
      mechanisms of antimicrobial action of micro-/nanoparticles and highlight the
      potential for bimetallic particle-based inhibition of microbial infections.

PMID- 29059531
TI  - Creatine Use in Sports.
AB  - CONTEXT: The use of creatine as a dietary supplement has become increasingly
      popular over the past several decades. Despite the popularity of creatine,
      questions remain with regard to dosing, effects on sports performance, and
      safety. EVIDENCE ACQUISITION: PubMed was searched for articles published between
      1980 and January 2017 using the terms creatine, creatine supplementation, sports
      performance, and dietary supplements. An additional Google search was performed
      to capture National Collegiate Athletic Association-specific creatine usage data
      and US dietary supplement and creatine sales. STUDY DESIGN: Clinical review.
      LEVEL OF EVIDENCE: Level 4. RESULTS: Short-term use of creatine is considered
      safe and without significant adverse effects, although caution should be advised
      as the number of long-term studies is limited. Suggested dosing is variable, with
      many different regimens showing benefits. The safety of creatine supplementation
      has not been studied in children and adolescents. Currently, the scientific
      literature best supports creatine supplementation for increased performance in
      short-duration, maximal-intensity resistance training. CONCLUSION: While creatine
      appears to be safe and effective for particular settings, whether creatine
      supplementation leads to improved performance on the field of play remains
      unknown.

PMID- 29059533
TI  - Factors associated with self-reported inattentive driving at highway-rail grade
      crossings.
AB  - This research identified factors associated with inattentive driving at Highway
      Rail Grade Crossings (HRGCs) by investigating drivers' self-reported inattentive
      driving experiences and factors pertaining to their socioeconomic, personality,
      attitudinal, and other characteristics. A random selection of 2500 households in
      Nebraska received a survey questionnaire designed for licensed motor vehicle
      drivers; respondents returned 980 questionnaires. Factor analysis identified
      latent variables evaluating drivers' patience and inclination to wait for trains,
      attitudes toward new technology, law enforcement or education regarding HRGC
      safety, and the propensity to commit serious traffic violations at HRGCs. The
      investigation utilized a structural equation model for analysis. This model
      indicated that drivers with a higher risk of inattentive driving at HRGCs were:
      female, younger in age, from households with higher incomes, with shorter tenure
      (in years) in their current city of residence, more frequently used HRGCs,
      received less information on safety at HRGCs, had less patience to wait for
      trains to pass and had less interest in safety improvement technology, law
      enforcement or safety education at HRGCs. These research findings provide useful
      information for future research and to policy makers for improving public safety.
      Additionally, the results are useful for safety educational program providers for
      targeted program delivery to drivers that are more vulnerable to distracted
      driving at HRGCs.

PMID- 29059532
TI  - Site-directed mutagenesis to deactivate two nitrogenase isozymes of Kosakonia
      radicincitans DSM16656T.
AB  - Biological nitrogen fixation (BNF) is considered one of the key plant-growth
      promoting (PGP) factors for diazotrophic organisms. Whether the iron and iron
      molybdenum nitrogenases of Kosakonia radicincitans contribute to its PGP effect
      is yet to be proven. Hence, for the first time, we conducted site-directed
      mutagenesis in K. radicincitans to knock out anfH and (or) nifH as a mean to
      deactivate BNF in this strain. We used 15N2-labeled air to trace BNF activities
      in DeltaanfH, DeltanifH, and DeltaanfHDeltanifH mutants. Assessing bacterial
      growth, nitrogen content, and 15N incorporation revealed that BNF is impaired in
      K. radicincitans DSM16656T DeltanifH and DeltaanfHDeltanifH. However, we detected
      no significant contribution of the Fe nitrogenase to biological dinitrogen
      assimilation under our pure bacterial culture experimental conditions. Such
      nondiazotrophic K. radicincitans DSM16656T mutants represent excellent tools for
      investigating nitrogen nutrition in K. radicincitans-inoculated plants.

PMID- 29059534
TI  - Use of prescription opioids and motor vehicle crashes: A meta analysis.
AB  - OBJECTIVES: Opioid analgesics are a major driver of the ongoing opioid epidemic
      in the United Sates, accounting for about two thirds of drug overdose fatalities.
      There are conflicting reports regarding the effects of prescription opioids on
      driving safety. A meta-analysis was performed to assess the epidemiologic
      evidence for the association between use of prescription opioids and the risk of
      motor vehicle crashes. METHODS: Studies examining the association between driver
      prescription opioid use and motor vehicle crash involvement or crash culpability
      and published in English were identified through a comprehensive search of 15
      bibliographic databases. Eligible articles were fully reviewed and summarized.
      Study quality was assessed using the Newcastle-Ottawa Scale. Overall summary odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated through random
      effects models. RESULTS: Overall, 15 studies were included in the meta-analysis;
      of them, 10 assessed the association of prescription opioid use with the risk of
      crash involvement and 5 assessed the association of prescription opioid use with
      the risk of crash culpability. Reported crude ORs associated with prescription
      opioid use ranged from 1.15 to 8.19 for the risk of crash involvement and from
      0.75 to 2.78 for the risk of crash culpability. Summary ORs based on pooled data
      were 2.29 (95% CI: 1.51, 3.48) for crash risk and 1.47 (95% CI: 1.01, 2.13) for
      crash culpability. CONCLUSIONS: The existent epidemiologic evidence indicates
      that use of prescription opioids by drivers is associated with significantly
      increased risks of crash involvement and crash culpability. Further research is
      needed to understand the epidemiologic patterns of prescription opioid use in the
      driver population and the interaction effects between opioids and alcohol on
      driving safety.

PMID- 29059535
TI  - Human reconstructed skin xenografts on mice to model skin physiology.
AB  - Xenograft models to study skin physiology have been popular for scientific use
      since the 1970s, with various developments and improvements to the techniques
      over the decades. Xenograft models are particularly useful and sought after due
      to the lack of clinically relevant animal models in predicting drug effectiveness
      in humans. Such predictions could in turn boost the process of drug discovery,
      since novel drug compounds have an estimated 8% chance of FDA approval despite
      years of rigorous preclinical testing and evaluation, albeit mostly in non-human
      models. In the case of skin research, the mouse persists as the most popular
      animal model of choice, despite its well-known anatomical differences with human
      skin. Differences in skin biology are especially evident when trying to dissect
      more complex skin conditions, such as psoriasis and eczema, where interactions
      between the immune system, epidermis and the environment likely occur. While the
      use of animal models are still considered the gold standard for systemic toxicity
      studies under controlled environments, there are now alternative models that have
      been approved for certain applications. To overcome the biological limitations of
      the mouse model, research efforts have also focused on "humanizing" the mice
      model to better recapitulate human skin physiology. In this review, we outline
      the different approaches undertaken thus far to study skin biology using human
      tissue xenografts in mice and the technical challenges involved. We also describe
      more recent developments to generate humanized multi-tissue compartment mice that
      carry both a functioning human immune system and skin xenografts. Such composite
      animal models provide promising opportunities to study drugs, disease and
      differentiation with greater clinical relevance.

PMID- 29059536
TI  - Guaianolide sesquiterpene lactones and aporphine alkaloids from the stem bark of
      Guatteria friesiana.
AB  - Three guaianolide sesquiterpenes, denoted guatterfriesols A-C, and four aporphine
      alkaloid derivatives were isolated from the stem bark of the Amazonian plant
      Guatteria friesiana. Thus far, sesquiterpene lactones have not been described in
      Annonaceae. Structures of the previously undescribed compounds were established
      by using 1D and 2D NMR spectroscopy in combination with MS. The absolute
      stereochemistry was assigned via NOE NMR experiments, ECD spectroscopy, and
      theoretical calculations using the TDDFT approach. Among the isolated compounds,
      the alkaloid guatterfriesidine showed anti-glycation activity by inhibiting the
      formation of advanced glycation end-products (AGEs) through the prevention of
      oxidation in both BSA/methylglyoxal and BSA/fructose systems.

PMID- 29059537
TI  - Investigation of the flavan-3-ol patterns in willow species during one growing
      season.
AB  - Flavonoids, proanthocyanidins (PAs) and salicylic alcohol derivatives are the
      main groups of ingredients in Salix needed as defensive tools and signal
      molecules, but have also pharmaceutical importance. The present study
      investigated total PA content, complete PA pattern, the oligomeric/total PAs
      quotient and the contents of catechin and epicatechin during one growing-season
      for the leaves and this year's sprouts in ten willows (Salix pentandra L. ?, S.
      alba L. ?, S. fragilis L. ?, S. caprea L. ? & ?, S. cinerea L. ?, S. caprea x
      cinerea ?, S. daphnoidesVill. ? & ? and S. purpurea L. ?; all Salicaceae).
      Comparison of the different species revealed distinct seasonal fluctuations of
      the oligomeric and polymeric PA fractions, but the contents of both groups always
      developed in the same direction. All willows prefer the synthesis of PAs with DP
      2 - DP-4 within the oligomeric fraction (DP-2 - DP-10) and species with rather
      low PA contents like S. purpurea (0.1-2.6 mg/g) as well as species with rather
      high PA contents like S. alba (3.8-14.7 mg/g) were found. Only slight gender
      specific differences could be observed for both sexes of S. daphnoides and S.
      caprea. The PA pattern of the hybrid S. caprea x cinerea seems to be influenced
      by both parents. Thus, the accumulation of the oligomeric PAs accorded to S.
      caprea and the polymeric PAs matched S. cinerea resulting in an overall
      depression of PAs in the sprouts and a varying seasonal trend in the leaves. In
      contrast, the content of catechin remained high and seemed to be not influenced
      in the hybrid. Although only one individual of each Salix species could be
      considered in this screening study, the present results demonstrate the
      variability of the flavan-3-ol pattern within the genus Salix but also some
      preliminary correlations could be observed. Future studies with more Salix
      species will provide more insights into chemotaxonomic correlations.

PMID- 29059539
TI  - Rosemary distillation residues reduce lipid oxidation, increase alpha-tocopherol
      content and improve fatty acid profile of lamb meat.
AB  - The experiment studied the effects of rosemary distillation residues (RR) intake
      on lamb meat quality, oxidative stability and fatty acid (FA) profile. Barbarine
      lambs of Control group were fed 600g of hay, which was substituted by 600g of
      pellets containing 60 and 87% of RR for RR60 and RR87 groups; all animals
      received 600g of concentrate. Meat protein and fat content was similar for 3
      treatments. Lipid oxidation was strongly reduced with RR diets. Both RR diets
      resulted in a higher alpha- tocopherol content in muscle. The metmyoglobin and
      deoxymyoglobin percentages were similar for all groups; however oxymyoglobin was
      higher for RR groups. The saturated (SFA) and unsaturated FAs (UFA) were
      unaffected by the diets. However, the PUFA, n-6 and n-3 were higher for RR
      groups. In conclusion, rosemary residues resulted in higher vitamin E content, so
      it enhanced the oxidative status and improved the fatty acid profile of lamb
      meat.

PMID- 29059538
TI  - Effects of the Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor
      associated musculoskeletal symptoms: A randomized, controlled clinical trial.
AB  - : Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) are prevalent
      among patients on AI therapy, which leads to a lower quality of life and poor
      adherence to AI treatment. We evaluated whether Yi Shen Jian Gu granules (YSJG)
      is effective and safe to relieve AIMSS in patients with breast cancer. Eligible
      participants were randomly assigned to the YSJG group or the placebo group. Both
      groups had a 12-week treatment period and a 12-week follow-up period. Brief Pain
      Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities
      Osteoarthritis (WOMAC) Index, and the Modified Score for the Assessment and
      Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) were
      obtained at baseline and at 4, 8, 12 and 24 weeks. Of 146 participants enrolled,
      84 were randomly assigned, and 77 were evaluable at 12 weeks. Baseline
      characteristics were comparable between two groups. The primary outcome was the
      differences in mean BPI-SF scores at 12 weeks. The worst pain scores decreased by
      3.10 points (50.2%; 95% CI, 2.50 to 3.65) for YSJG group compared with a 1.63
      point decrease (26.9%; 95% CI, 3.86 to 4.97) for the placebo group (P = 0.001).
      Significantly improvements were also observed for the WOMAC and M-SACRAH.
      Possibly YSJG-related side effects were grade 1 nausea (10%) and grade 2 diarrhea
      (2%). Serum follicle-stimulating hormone and serum estradiol were kept in the
      postmenopausal range before and after YSJG treatment. Patients with AIMSS treated
      with YSJG granules had significant improvements in musculoskeletal symptoms. YSJG
      is effective, safe and well-tolerated in managing AIMSS. TRIAL REGISTRATION:
      ISCTN: ISRCTN06129599 (assigned 14 August 2013).

PMID- 29059540
TI  - Intratumoral injection of thermogelling and sustained-release carboplatin-loaded
      hydrogel simplifies the administration and remains the synergistic effect with
      radiotherapy for mice gliomas.
AB  - BACKGROUND: Carboplatin, an antineoplastic agent, binds DNA and enhances
      radiotherapy (RT) effects. Carboplatin-loaded hydrogel (oxidized hyaluronic
      acid/adipic acid dihydrazide) enables the sustained drug release and facilitates
      the synergistic effect with RT. PURPOSE: We investigated the effectiveness and
      convenience of hydrogel carboplatin combined with RT for mice glioma. MATERIALS
      AND METHODS: Mouse glioma cells (ALTS1C1) were subcutaneously implanted in the
      right thigh of C57BL/6 mice on Day 0. The mice were categorized by treatments:
      sham, hydrogel, hydrogel carboplatin, aqueous carboplatin, RT, hydrogel
      carboplatin/RT, and aqueous carboplatin/RT. Hydrogel carboplatin (300 MUg single
      dose on Day 7) or aqueous carboplatin (100 MUg daily dose on Days 7, 8, and 9)
      was administered via intratumoral injection. RT was delivered a daily dose of 10
      Gy on Days 8 and 9. RESULTS: For mice administered hydrogel carboplatin/RT versus
      those administered aqueous carboplatin/RT, the 24-day tumor growth control rate
      and 104-day recurrence-free survival rate were 100% and 50% versus 100% and 66.7%
      (p = 0.648), respectively. However, mice receiving other treatments showed tumor
      progression by Day 24 and died within 40 days of tumor cell implantation.
      CONCLUSIONS: Hydrogel carboplatin simplified intratumoral drug delivery and
      remained the synergistic effects with RT, which is potential for clinical
      applications.

PMID- 29059542
TI  - Perceived stress moderates the effects of a randomized trial of dance movement
      therapy on diurnal cortisol slopes in breast cancer patients.
AB  - Women with breast cancer are at risk of psychosocial distress and may suffer from
      aberrant diurnal cortisol rhythms. Dance movement therapy (DMT), a movement-based
      psychotherapy that incorporates exercise and artistic components, has
      demonstrated stress reduction effects. This study examined the effects of DMT on
      the diurnal cortisol rhythms of breast cancer patients undergoing radiotherapy
      treatment and the role of perceived stress in producing such effects. The study
      sample comprised 121 Chinese breast cancer patients randomized to the DMT (n=63)
      and control (n=58) groups. The intervention consisted of six 1.5-h group sessions
      held twice weekly over the course of radiotherapy. Participants completed
      validated self-report measures of perceived stress, fatigue, pain, and sleep
      disturbance and provided five salivary cortisol samples at baseline (Time 1) and
      post-intervention (Time 2). Moderated mediation analysis was used to evaluate the
      intervention effect on Time 2 diurnal cortisol slopes. Despite the absence of a
      significant DMT effect on diurnal cortisol slopes (B=-0.55, 95% CI=-1.20 to 0.08,
      beta=-0.14), baseline perceived stress significantly moderated the intervention
      effect (B=-0.18, 95% CI=-0.32 to -0.05, beta=-0.30). At high levels of baseline
      perceived stress (1 SD above the mean), the DMT group showed a steeper cortisol
      slope (M=-7.14) than the control group (M=-5.80) at Time 2. The present findings
      suggest that DMT might have a beneficial effect on diurnal cortisol slopes in
      breast cancer patients with high levels of distress.

PMID- 29059543
TI  - Spread the word: MMN brain response reveals whole-form access of discontinuous
      particle verbs.
AB  - The status of particle verbs such as rise (...) up as either lexically stored or
      combinatorially assembled is an issue which so far has not been settled
      decisively. In this study, we use the mismatch negativity (MMN) brain response to
      observe neurophysiological responses to discontinuous particle verbs. The MMN can
      be used to distinguish between whole-form storage and combinatorial processes, as
      it is enhanced to stored words compared to unknown pseudowords, whereas
      combinatorially legal strings elicit a reduced MMN relative to ungrammatical
      ones. Earlier work had found larger MMNs to congruent than to incongruent verb
      particle combinations when particle and verb appeared as adjacent elements, thus
      suggesting whole-form storage at least in this case. However, it is still
      possible that particle verbs discontinuously spread out across a sentence would
      elicit the combinatorial, grammar-violation response pattern instead. Here, we
      tested the brain signatures of discontinuous verb-particle combinations,
      orthogonally varying congruence and semantic transparency. The results show for
      the first time brain indices of whole-form storage for discontinuous
      constituents, thus arguing in favour of access to whole-form-stored lexical
      elements in the processing of particle verbs, irrespective of their semantic
      opacity. Results are discussed in the context of linguistic debates about the
      status of particle verbs as words, lexical elements or syntactically generated
      combinations. The explanation of the pattern of results within a neurobiological
      language model is highlighted.

PMID- 29059541
TI  - Creation of a nanoformulated cabotegravir prodrug with improved antiretroviral
      profiles.
AB  - Long-acting parenteral (LAP) antiretroviral drugs have generated considerable
      interest for treatment and prevention of HIV-1 infection. One new LAP is
      cabotegravir (CAB), a highly potent integrase inhibitor, with a half-life of up
      to 54 days, allowing for every other month parenteral administrations. Despite
      this excellent profile, high volume dosing, injection site reactions and low body
      fluid drug concentrations affect broad use for virus infected and susceptible
      people. To improve the drug delivery profile, we created a myristoylated CAB
      prodrug (MCAB). MCAB formed crystals that were formulated into nanoparticles
      (NMCAB) of stable size and shape facilitating avid monocyte-macrophage entry,
      retention and reticuloendothelial system depot formulation. Drug release kinetics
      paralleled sustained protection against HIV-1 challenge. After a single 45 mg/kg
      intramuscular injection to BALB/cJ mice, the NMCAB pharmacokinetic profiles was 4
      times greater than that recorded for CAB LAP. These observations paralleled
      replicate measurements in rhesus macaques. The results coupled with improved
      viral restriction in human adult lymphocyte reconstituted NOD/SCID/IL2Rgammac-/-
      mice led us to conclude that NMCAB can improve biodistribution and viral
      clearance profiles upon current CAB LAP formulations.

PMID- 29059544
TI  - Neural oscillatory mechanisms during novel grammar learning underlying language
      analytical abilities.
AB  - The goal of the present study was to investigate the initial phases of novel
      grammar learning on a neural level, concentrating on mechanisms responsible for
      individual variability between learners. Two groups of participants, one with
      high and one with average language analytical abilities, performed an Artificial
      Grammar Learning (AGL) task consisting of learning and test phases. During the
      task, EEG signals from 32 cap-mounted electrodes were recorded and epochs
      corresponding to the learning phases were analysed. We investigated spectral
      power modulations over time, and functional connectivity patterns by means of a
      bivariate, frequency-specific index of phase synchronization termed Phase Locking
      Value (PLV). Behavioural data showed learning effects in both groups, with a
      steeper learning curve and higher ultimate attainment for the highly skilled
      learners. Moreover, we established that cortical connectivity patterns and
      profiles of spectral power modulations over time differentiated L2 learners with
      various levels of language analytical abilities. Over the course of the task, the
      learning process seemed to be driven by whole-brain functional connectivity
      between neuronal assemblies achieved by means of communication in the beta band
      frequency. On a shorter time-scale, increasing proficiency on the AGL task
      appeared to be supported by stronger local synchronisation within the right
      hemisphere regions. Finally, we observed that the highly skilled learners might
      have exerted less mental effort, or reduced attention for the task at hand once
      the learning was achieved, as evidenced by the higher alpha band power.

PMID- 29059545
TI  - The effect of without using anisodamine during CT enterography on image quality,
      diagnostic performance and latent side effects.
AB  - OBJECTIVE: To examine whether no anisodamine injection before CTE was feasible
      without impairing image quality and diagnostic performance. MATERIALS: The change
      of mural thickness and luminal diameter were compared between using and no using
      anisodamine. The diagnostic performance of small-bowel disease was analyzed and
      compared. RESULTS: No motion artifact was detected in two groups. There was no
      significant difference regarding the change of luminal diameter and mural
      thickness (all P>0.05). The diagnostic accuracy of small-bowel disease was no
      significant difference (P=0.63). CONCLUSION: Lack of anisodamine injection before
      CTE did not impair image quality and diagnostic performance compared with CTEs
      performed with anisodamine injection.

PMID- 29059546
TI  - Mimics of acute appendicitis-Alternative diagnoses at sonography, CT, and MRI;
      specific imaging findings that can help in differential diagnosis.

PMID- 29059547
TI  - Forensic DNA typing from teeth using demineralized root tips.
AB  - Teeth are widely used samples in forensic human genetic identification due to
      their persistence and practical sampling and processing. Their processing,
      however, has changed very little in the last 20 years, usually including
      powdering or pulverization of the tooth. The objective of this study was to
      present demineralized root tips as DNA sources while, at the same time, not
      involving powdering the samples or expensive equipment for teeth processing. One
      to five teeth from each of 20 unidentified human bodies recovered from midwest
      Brazil were analyzed. Whole teeth were demineralized in EDTA solution with daily
      solution change. After a maximum of approximately seven days, the final
      millimeters of the root tip was excised. This portion of the sample was used for
      DNA extraction through a conventional organic protocol. DNA quantification and
      STR amplification were performed using commercial kits followed by capillary
      electrophoresis on 3130 or 3500 genetic analyzers. For 60% of the unidentified
      bodies (12 of 20), a full genetic profile was obtained from the extraction of the
      first root tip. By the end of the analyses, full genetic profiles were obtained
      for 85% of the individuals studied, of which 80% were positively identified. This
      alternative low-tech approach for postmortem teeth processing is capable of
      extracting DNA in sufficient quantity and quality for forensic casework, showing
      that root tips are viable nuclear DNA sources even after demineralization.

PMID- 29059548
TI  - Enhanced pseudocapacitance performance of conductive polymer electroactive film
      in the presence of green compound of 1-Butyl-3-methylimidazolium Chloride:
      Electrochemical and DFT study.
AB  - In present work, for improving the electrochemical performance of conductive
      polymer, poly ortho aminophenol (POAP)/1-Butyl-3-methylimidazolium Chloride,
      [bmim]Cl composite films have been fabricated by POAP electropolymerization in
      the presence of [bmim]Cl as active electrodes for electrochemical
      supercapacitors. Different electrochemical methods including galvanostatic charge
      discharge experiments, cyclic voltammetry and electrochemical impedance
      spectroscopy have been applied to study the system performance. Analysis of DFT
      B3LYP/6-31G* computational results, and AIM (atom-in-molecule) theory
      calculations, show that the atomic-scale electronic properties are generally
      depend on the bonding and electronic molecular structures (and thus their
      variation with the external bias in real nano-electrochemical circuits). The
      supercapacity behavior of the composite film was attributed to the (i) high
      active surface area of the composite, (ii) charge transfer along the polymer
      chain due to the conjugation form of the polymer and finally (iii) synergism
      effect between conductive polymer and [bmim]Cl.

PMID- 29059549
TI  - Synthesis of high volumetric capacity graphene oxide-supported tellurantimony Na-
      and Li-ion battery anodes by hydrogen peroxide sol gel processing.
AB  - High-charge-capacity sodium-ion battery anodes made of Sb2Te3@reduced graphene
      oxide are reported for the first time. Uniform nano-coating of graphene oxide is
      carried out from common sol of peroxotellurate and peroxoantimonate under room
      temperature processing. Reduction by hydrazine under glycerol reflux yields
      Sb2Te3@reduced graphene oxide. The electrodes exhibit exceptionally high
      volumetric charge capacity, above 2300mAhcm-3 at 100mAg-1 current density,
      showing very good rate capabilities and retaining 60% of this capacity even at
      2000mAg-1. A comparison of sodiation and lithiation shows that lithiation
      exhibits better volumetric charge capacity, but surprisingly only marginally
      better relative rate capability retention at 2000mAg-1. Tellurium-based
      electrodes are attractive due to the high volumetric charge capacity of Te, its
      very high electric conductivity, and the low relative expansion upon
      lithiation/sodiation.

PMID- 29059550
TI  - Catalytic decomposition of 2-chlorophenol using an ultrasonic-assisted Fe3O4
      TiO2@MWCNT system: Influence factors, pathway and mechanism study.
AB  - As a reusable sonocatalyst, magnetically separable Fe3O4-TiO2@MWCNT (FMT) was
      synthesized by an ultrasound-assisted wet impregnation method and was evaluated
      in the removal of 2-chlorophenol (2CP). Physical and chemical properties of the
      catalyst composite materials were investigated by all catalysts were
      systematically characterized using Transmission Electron Microscopy (TEM), X-ray
      diffraction (XRD), Scanning Electron Microscopy (SEM), X-ray Photoelectron
      Spectroscopy (XPS), Energy Dispersive X-ray Analysis (EDX), Dynamic light
      scattering (DLS), and N2-physisorption. The efficiency and kinetics of 2CP
      removal by FMT-assisted sonocatalysis (FMT-US) was systematically investigated
      under various operational parameters i.e. pH, FMT and 2CP concentration,
      temperature and ultrasonic power. The results indicated that 0.4gL-1 FMT dosage,
      pH 5, temperature of 35 degrees C as well as 50 w ultrasound power are the most
      favorable conditions for the degradation of the 2CP. Furthermore, both of the
      superoxide and hydroxyl radicals were produced in the reaction, however,
      superoxide radicals were assumed to be the dominating reactive species for the
      2CP degradation, according to the scavenging tests and electron paramagnetic
      resonance tests. Moreover, the FMT catalyst exhibited a high reusability and
      stability in the US/FMT system during the five repetitive experiments. The
      intermediate products were identified by GC-MS, thereby a possible degradation
      pathway is proposed. The chemical oxygen demand (COD) and corresponding total
      organic carbon (TOC) removal efficiencies were 64.9% and 56.7%, respectively.
      Finally, toxicity tests showed that the toxicity of the solution increased during
      the first 5min and then decreased significantly with the progress of the
      oxidation. The mechanisms of ultrasound irritation enhanced FMT activation were
      also proposed.

PMID- 29059551
TI  - Treatment of methylene blue containing wastewater by a cost-effective micro-scale
      biochar/polysulfone mixed matrix hollow fiber membrane: Performance and mechanism
      studies.
AB  - Dye containing wastewater has increasingly become an important contamination due
      to operation of various industries such as textile industry. In this study, a
      micro-scale biochar particles/polysulfone mixed matrix hollow fiber membrane
      (MMM) was applied for the removal of methylene blue from water. The static and
      dynamic adsorption performance was investigated. We found that the MMM exhibited
      a high removal efficiency of methylene blue under a wide pH range of 4-10. The
      adsorption process on biochar and MMM obeyed the intraparticle surface diffusion
      model and Langmuir isotherm model. At neutral pH, the maximum adsorption capacity
      was 544.459 mg/g for biochar and 165.808 mg/g for MMM. Better regeneration with a
      desorption rate above 92% was achieved by 1-M NaCl in 90% ethanol aqueous
      solution. Furthermore, the MMM displayed good performance in treating methylene
      blue containing wastewater through a continuous filtration mode. More
      importantly, the MMM showed an excellent reusability for methylene blue removal;
      it was able to achieve 81% of the permeate yield of the fresh MMM after three
      regeneration cycles. Finally, the adsorption mechanism studies indicated that the
      removal of methylene blue was associated with electrostatic interaction, hydrogen
      bonding and hydrophobic interaction.

PMID- 29059552
TI  - Protective composite silica/polyelectrolyte shell with enhanced tolerance to
      harsh acid and alkali conditions.
AB  - Here we report a facile method to fabricate composite polymeric/inorgainc shells
      consisting of poly(allylamine hydrochloride) (PAH)/poly-(sodium 4
      styrenesulfonate) (PSS) multilayers strengthed by the in situ formed silica
      (SiO2) nanoparticles (NPs), achieving an enhanced stability under harsh acidic
      and basic conditions. While the unsiliconised PAH/PSS multilayers show a pH
      dependent stability and permeability, the composite PAH/PSS/SiO2 shells display
      significantly higher chemical tolerance towards a variety of harsh conditions (1
      <= pH <= 13, high salinity). Upon treatment with either hydrochloric acid (HCl,
      pH=1) or 0.2 M ethylenediaminetetraacetic acid disodium salt (EDTA, weak acid,
      chelator), the (PAH/PSS)6/SiO2 shells are able to maintain the integrity of most
      calcium carbonate (CaCO3) particles, as the shells are tickened and densified by
      sufficient SiO2 NPs. When treated with NaOH solution at pH=13, the
      (PAH/PSS)6/SiO2 shells also display an intact morphology and maintain the ability
      to intercept rhodamin B (Rh-B) molecules, which is quite different to that
      observed with the unsiliconised (PAH/PSS)6 shells. Ultrasound is proved to
      rapidly break the composite shells, hence can be used as a potential stimulus to
      trigger the release of encapsulated substances. All the results demonstrate the
      fact that the composite (PAH/PSS)6/SiO2 shells have a higher chemical stability,
      lower permeability for small molecules and a greater sensitivity to ultrasound,
      which is promising for many applications where protecting the activity of small
      molecules is required, such as the delivery of encapsulated drugs in an
      unhindered form to their specific destination within the human body.

PMID- 29059553
TI  - Design and construction of a quadruple-resonance MAS NMR probe for investigation
      of extensively deuterated biomolecules.
AB  - Extensive deuteration is frequently used in solid-state NMR studies of
      biomolecules because it dramatically reduces both homonuclear (1H-1H) and
      heteronuclear (1H-13C and 1H-15N) dipolar interactions. This approach greatly
      improves resolution, enables low-power rf decoupling, and facilitates 1H-detected
      experiments even in rigid solids at moderate MAS rates. However, the resolution
      enhancement is obtained at some cost due the reduced abundance of protons
      available for polarization transfer. Although deuterium is a useful spin-1 NMR
      nucleus, in typical experiments the deuterons are not directly utilized because
      the available probes are usually triple-tuned to 1H,13C and 15N. Here we describe
      a 1H/13C/2H/15N MAS ssNMR probe designed for solid-state NMR of extensively
      deuterated biomolecules. The probe utilizes coaxial coils, with a modified
      Alderman-Grant resonator for the 1H channel, and a multiply resonant solenoid for
      13C/2H/15N. A coaxial tuning-tube design is used for all four channels in order
      to efficiently utilize the constrained physical space available inside the magnet
      bore. Isolation among the channels is likewise achieved using short, adjustable
      transmission line elements. We present benchmarks illustrating the tuning of each
      channel and isolation among them and the magnetic field profiles at each
      frequency of interest. Finally, representative NMR data are shown demonstrating
      the performance of both the detection and decoupling circuits.

PMID- 29059555
TI  - Comparison of the effects of chloramine and chlorine on the aromaticity of
      dissolved organic matter and yields of disinfection by-products.
AB  - This study compared effects of chlorination and chloramination on the
      chromophores of dissolved organic matter (DOM) and attendant formation of
      disinfection by-products (DBPs) in raw and treated surface waters. Comparison of
      the differential absorbance spectra of chloraminated and chlorinated waters shows
      that interactions of chloramine with DOM chromophores result in changes that are
      in many respects similar to those observed for chlorine although the extent of
      degradation of DOM chromophores and the attendant decrease of DOM aromaticity by
      chloramine are less pronounced than that caused by free chlorine. The degradation
      of DOM chromophores caused by the examined disinfectants indicated that in both
      cases a gradual decrease of DOM took place. Decreases of DOM aromaticity
      estimated based on the changes of DOM absorbance at 254 or 280 nm were correlated
      with chlorine consumption in a similar way for both examined disinfectants.
      Correlations between changes of DOM absorbance and yields of dihaloacetic acids
      (DHAA) were also similar for chlorination and chloramination. This was
      interpreted to indicate that the generation of DHAA proceeds via the degradation
      of the reactive sites associated with DOM chromophores irrespective of whether
      these sites are engaged by chlorine or chloramine. Correlations between the
      decrease of DOM aromaticity and formation of other DBP (e.g. trihalomethanes -
      THM, trihaloacetic acids - THAA and dihaloacetonitriles - DHAN) for chloramine
      and chlorine were also observed but, as opposed to the observations for DHAA, the
      correlations between degradation of DOM aromaticity and yields of THM, THAA or
      DHAN were different for chlorination and chloramination.

PMID- 29059554
TI  - Regulation by S-nitrosylation of the Calvin-Benson cycle fructose-1,6
      bisphosphatase in Pisum sativum.
AB  - Redox regulation is of great importance in chloroplasts. Many chloroplast
      enzymes, such as those belonging to the Calvin-Benson cycle (CBC), have conserved
      regulatory cysteines which form inhibitory disulphide bridges when physiological
      conditions become unfavourable. Amongst these enzymes, cFBP1, the CBC fructose
      1,6-bisphosphatase (FBPase) isoform, is well known to be redox activated by
      thioredoxin f through the reduction of a disulphide bridge involving Cys153 and
      Cys173. Moreover, data obtained during recent years point to S-nitrosylation as
      another redox post-translational modification putatively regulating an increasing
      number of plant enzymes, including cFBP1. In this study we have shown that the
      Pisum sativum cFBP1 can be efficiently S-nitrosylated by GSNO and SNAP,
      triggering the formation of the regulatory disulphide. Using in vivo experiments
      with P. sativum we have established that cFBP1 S-nitrosylation only occurs during
      the light period and we have elucidated by activity assays with Cys-to-Ser
      mutants that this enzyme may be inactivated through the S-nitrosylation of
      Cys153. Finally, in the light of the new data, we have proposed an extended redox
      regulation model by integrating the S-nitrosylation and the TRX f-mediated
      regulation of cFBP1.

PMID- 29059556
TI  - Permanganate with a double-edge role in photodegradation of sulfamethoxazole:
      Kinetic, reaction mechanism and toxicity.
AB  - In this study, the double-edge role of permanganate in sulfamethoxazole (SMX)
      photodegradation with a recyclable catalyst was revealed for the first time. The
      role of the catalyst under different UV wavelength, the role of permanganate in
      the treatment process, the effects of permanganate dosage and solution pH on the
      removal efficiency were investigated. Moreover, the transformation products, TOC
      reduction and the toxicity of the treated final product to Chlorella vulgaris and
      Artemia salina were determined. Sole permanganate showed no effect in SMX
      degradation, while its introduction to the photocatalytic process doubled the
      reaction rate at the optimal dosage. It is interesting to find that the reaction
      rate showed a fluctuation trend in terms of permanganate dosage due to the
      summation of positive effect of permanganate oxidation and the negative effect of
      the formed MnO2 at the surface of the catalyst, as well as the light attenuation
      due to overdosed permanganate. The determined intermediates, the higher inorganic
      ions release and TOC reduction provided a clue on a higher mineralization
      compared to SMX degradation in the same process without permanganate.
      Permanganate above 1 MUM may pose a threat to the algae growth, therefore a good
      monitoring and control of residual permanganate dosage should be incorporated
      into the process design. A good toxicity reduction to A. salina was observed in
      the treated effluent; a longer detention is suggested for the complete removal of
      toxicity.

PMID- 29059557
TI  - Magnetic Fe3O4@V2O5/rGO nanocomposite as a recyclable photocatalyst for dye
      molecules degradation under direct sunlight irradiation.
AB  - Reduced graphene oxide nanosheets decorated with Fe3O4 and V2O5 nanoparticles as
      a magnetically recoverable nanocomposite (Fe3O4@V2O5/rGO) was synthesized by a
      simple solution chemistry approach. The synthesized nanocomposite was
      characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS),
      vibrating sample magnetometer (VSM), Fourier transform infrared (FTIR),
      fluorescence, and zeta potential measurements. The narrow band gap and different
      band gap energies of Fe3O4 and V2O5 proved to be suitable for the absorption of
      visible light in the solar spectrum. The Fe3O4@V2O5/rGO displayed indeed
      excellent photocatalytic activity towards the degradation of harmful cationic
      Bismarck Brown (BB) as well as anionic Acid Orange 7 (AO) dyes under direct
      sunlight irradiation. The photocatalytic activity of the Fe3O4@V2O5/rGO is
      influenced by solution pH, catalyst loading, initial dye concentration and the
      presence of different inorganic ions (NH4+, Na+, Mg2+, Ca2+, SO42-, Br-, NO3-, Cl
      , HCO3-). This study provides a new scientific knowledge on the sunlight driven
      photocatalytic degradation of dye molecules using novel mixed metal oxide/rGO
      nanocomposite photocatalyst.

PMID- 29059558
TI  - Dioxin concentrations in dietary supplements containing animal oil on the
      Japanese market between 2007 and 2014.
AB  - We determined the concentrations of dioxins (polychlorinated dibenzo-p-dioxins,
      dibenzofurans and dioxin-like polychlorinated biphenyls) in 46 dietary supplement
      products, containing the oil of fish, marine mammals, or egg yolk, on the
      Japanese market between 2007 and 2014. Dioxins were detected in 43 of the 46
      products tested at concentrations from 0.00015 to 67 pg TEQ/g. The highest
      concentration of dioxins was found in a shark liver oil product which varied
      insignificantly in five batches collected over a two-year period. The dioxin
      intakes from these five batches reached 2.3-2.8 pg TEQ/kg bw/day, or 58%-70%,
      respectively, of the Japanese tolerable daily intake (TDI) of 4 pg TEQ/kg bw/day.
      However, the dioxin intakes from most of the other products tested were less than
      5% of the TDI. Although rare, supplements based on animal oils may contain
      relatively high concentrations of dioxins, leading to a substantial increase in
      dioxin intakes.

PMID- 29059559
TI  - Releasing characteristics and fate of heavy metals from phytoremediation crop
      residues during anaerobic digestion.
AB  - In this study, lab-scale batch tests were conducted to investigate releasing
      characteristics of heavy metals according to degradation of heavy metal
      containing biomass. The fate of heavy metals after released from biomass was also
      determined through adsorption tests and Visual MINTEQ simulation. According to
      the anaerobic batch test results as well as volatile solids and carbon balance
      analyses, maximum of 60% by wt. of biomass was degraded. During the anaerobic
      biodegradation, among Cd, Cu, Ni, Pb, and Zn, only Cu and Zn were observed in
      soluble form (approximately 40% by wt. of input mass). The discrepancy between
      degradation ratio of biomass and ratio of released heavy metals mass from biomass
      was observed. It seems that this discordance was caused by the fate (i.e.,
      precipitated with sulfur/hydroxide or adsorbed onto sorbents) of each heavy metal
      types in solution after being released from biomass. Thus, releasing
      characteristics and fate of heavy metal should be considered carefully to predict
      stability of anaerobic digestion process for heavy metal-containing biomass.

PMID- 29059560
TI  - Simultaneous removal of Cr(VI) and acid orange 7 from water solution by
      dielectric barrier discharge plasma.
AB  - A feasibility study was conducted for simultaneous removal of hexavalent chromium
      (Cr(VI)) and azo dye acid orange 7 (AO7) by the dielectric barrier discharge
      (DBD) plasma. The results showed that there was a synergistic effect between
      Cr(VI) reduction and AO7 degradation. The presence of Cr(VI) enhanced the
      degradation efficiency of AO7. Meanwhile, the removal efficiency of Cr(VI) also
      increased in the presence of AO7. Under acidic conditions (pH = 3.0), the
      reduction efficiency of Cr(VI) was higher (approximately 94%). However, the
      presence of Cr(VI) diminished the effect of pH on the AO7 degradation efficiency.
      By increasing the input voltage from 80 to 120 V, the removal efficiencies of
      Cr(VI) and AO7 were observably increased from 54% to 88% and 62% to 89%,
      respectively. Adding organic matters inhibited the degradation of AO7 and
      promoted the reduction of Cr(VI). The addition of Cu(II), Co(II), Ni(II), Mn(II)
      and Fe(III) could inhibit the Cr(VI) reduction, but not significantly affect the
      degradation of AO7. The degradation intermediates of AO7 were identified by LC
      MS/MS system and a possible degradation pathway was proposed. This study showed
      that the DBD plasma can simultaneously remove Cr(VI) and AO7, which provided a
      new idea for the actual wastewater treatment.

PMID- 29059561
TI  - Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney
      cells.
AB  - Chlorpyrifos (CPF) [O, O-diethyl -O-3, 5, 6-trichloro-2-pyridyl phosphorothioate]
      is an organophosphate insecticide widely used for agricultural and urban pest
      control. Trichloropyridinol (TCP; 3,5,6-trichloro-2-pyridinol), the primary
      metabolite of CPF, is often used as a generic biomarker of exposure for CPF and
      related compounds. Human embryonic kidney 293 (HEK 293) cells were exposed to CPF
      and TCP with varying concentrations and exposure periods. Cell cultures enable
      the cost-effective study of specific biomarkers to help determine toxicity
      pathways to predict the effects of chemical exposures without relying on whole
      animals. Both CPF and TCP were found to induce cytotoxic effects with CPF being
      more toxic than TCP with EC50 values of 68.82 MUg/mL and 146.87 MUg.ml-1
      respectively. Cell flow cytometric analyses revealed that exposure to either CPF
      or TCP leads to an initial burst of apoptotic induction followed by a slow
      recruitment of cells leading towards further apoptosis. CPF produced a strong
      induction of IL6, while TCP exposure resulted in a strong induction of IL1alpha.
      Importantly, the concentrations of CPF and TCP required for these cytokine
      inductions were higher than those required to induce apoptosis. These data
      suggest CPF and TCP are cytotoxic to HEK 293 cells but that the mechanism may not
      be related to an inflammatory response. CPF and TCP also varied in their effects
      on the HEK 293 proteome with 5 unique proteins detected after exposure to CPF and
      31 unique proteins after TCP exposure.

PMID- 29059562
TI  - Analytical transmission cross-coefficients for pink beam X-ray microscopy based
      on compound refractive lenses.
AB  - Analytical expressions for the transmission cross-coefficients for x-ray
      microscopes based on compound refractive lenses are derived based on Gaussian
      approximations of the source shape and energy spectrum. The effects of partial
      coherence, defocus, beam convergence, as well as lateral and longitudinal
      chromatic aberrations are accounted for and discussed. Taking the incoherent
      limit of the transmission cross-coefficients, a compact analytical expression for
      the modulation transfer function of the system is obtained, and the resulting
      point, line and edge spread functions are presented. Finally, analytical
      expressions for optimal numerical aperture, coherence ratio, and bandwidth are
      given.

PMID- 29059563
TI  - A quantitative method for measuring small residual beam tilts in high-resolution
      transmission electron microscopy.
AB  - In a transmission electron microscope, electron illumination beam tilt, or the
      degree of deviation of electron beam from its optical axis, is an important
      parameter that has a significant impact on image contrast and image
      interpretation. Although a large beam tilt can easily be noticed and corrected by
      the standard alignment procedure, a small residual beam tilt is difficult to
      measure and, therefore, difficult to account for quantitatively. Here we report a
      quantitative method for measuring small residual beam tilts, including its
      theoretical schemes, numerical simulation testing and experimental verification.
      Being independent of specimen thickness and taking specimen drifts into account
      in measurement, the proposed method is supplementary to the existing "rotation
      center" and "coma-free" alignment procedures. It is shown that this method can
      achieve a rather good accuracy of 94% in measuring small residual beam tilts of
      about 0.1 degrees  or less.

PMID- 29059564
TI  - Concept and design of a beam blanker with integrated photoconductive switch for
      ultrafast electron microscopy.
AB  - We present a new method to create ultrashort electron pulses by integrating a
      photoconductive switch with an electrostatic deflector. This paper discusses the
      feasibility of such a system by analytical and numerical calculations. We argue
      that ultrafast electron pulses can be achieved for micrometer scale dimensions of
      the blanker, which are feasible with MEMS-based fabrication technology. According
      to basic models, the design presented in this paper is capable of generating 100
      fs electron pulses with spatial resolutions of less than 10 nm. Our concept for
      an ultrafast beam blanker (UFB) may provide an attractive alternative to perform
      ultrafast electron microscopy, as it does not require modification of the
      microscope nor realignment between DC and pulsed mode of operation. Moreover,
      only low laser pulse energies are required. Due to its small dimensions the UFB
      can be inserted in the beam line of a commercial microscope via standard entry
      ports for blankers or variable apertures. The use of a photoconductive switch
      ensures minimal jitter between laser and electron pulses.

PMID- 29059565
TI  - Sludge reduction by ozone: Insights and modeling of the dose-response effects.
AB  - Applying ozone to the return flow in an activated sludge (AS) process is a way
      for reducing the residual solids production. To be able to extend the activated
      sludge models to the ozone-AS process, adequate prediction of the tri-atoms
      effects on the particulate COD fractions is needed. In this study, the biomass
      inactivation, COD mineralization, and solids dissolution were quantified in batch
      tests and dose-response models were developed as a function of the reacted ozone
      doses (ROD). Three kinds of model-sludge were used. S1 was a lab-cultivated
      synthetic sludge with two components (heterotrophs XH and XP). S2 was a digestate
      of S1 almost made by the endogenous residues, XP. S3 was from a municipal
      activated sludge plant. The specific ozone uptake rate (SO3UR, mgO3/gCOD.h) was
      determined as a tool for characterizing the reactivity of the sludges. SO3UR
      increased with the XH fraction and decreased with more XP. Biomass inactivation
      was exponential (e-beta.ROD) as a function of the ROD doses. The percentage of
      solids reduction was predictable through a linear model (CMiner + Ysol ROD), with
      a fixed part due to mineralization (CMiner) and a variable part from the
      solubilization process. The parameters of the models, i.e. the inactivation and
      the dissolution yields (beta, 0.008-0.029 (mgO3/mgCODini)-1 vs Ysol, 0.5-2.8 mg
      CODsol/mgO3) varied in magnitude, depending on the intensity of the scavenging
      reactions and potentially the compactness of the flocs for each sludge.

PMID- 29059566
TI  - Landscape biodiversity correlates with respiratory health in Australia.
AB  - Megatrends of urbanisation and reducing contact with natural environments may
      pose a largely unappreciated risk to human health, particularly in children,
      through declining normal (healthy) immunomodulatory environmental exposures. On
      the other hand, building knowledge of connections between environments,
      biodiversity and human health may offer new integrated ways of addressing global
      challenges of rising population health costs and declining biodiversity. In this
      study we are motivated to build insight and provide context and priority for
      emerging research into potential protective (e.g. immunomodulatory) environmental
      exposures. We use respiratory health as a test case to explore whether some types
      and qualities of environment may be more beneficial than others, and how such
      exposures may compare to known respiratory health influences, via a cross
      sectional ecological epidemiology study for the continent of Australia. Using
      Lasso penalized regression (to interpret key predictors from many candidate
      variables) and 10-fold cross-validation modelling (to indicate reproducibility
      and uncertainty), within different socio-geographic settings, our results show
      surrogate measures of landscape biodiversity correlate with respiratory health,
      and rank amongst known predictors. A range of possible drivers for this
      relationship are discussed. Perhaps most novel and interesting of these is the
      possibility of protective immunomodulatory influence from microbial diversity
      (suggested by the understudied 'biodiversity hypothesis') and other bioactive
      agents associated with biodiverse environments. If beneficial influences can be
      demonstrated from biodiverse environments on immunomodulation and human health,
      there may be potential to design new cost-effective nature-based health
      intervention programs to reduce the risk of immune-related disease at a
      population level. Our approach and findings are also likely to have use in the
      evaluation of environment and health associations elsewhere.

PMID- 29059567
TI  - Cultural dimensions of risk perceptions: A case study on cross-strait driftage
      pollution in a coastal area of Taiwan.
AB  - Constant exploitations of the ocean render numerous present challenges as the
      ocean is linked to human development. The study focused on cross-strait driftage
      pollution that poses a great threat to coastal environment under climate change.
      Several hundred packs of herbicides drifting across the Taiwan Strait were
      discovered along the coastline of Guanyin District of Taiwan. We compared risk
      perceptions of the local ethnic groups, Hakka and Fulao, residing in a coastal
      area of Taiwan and exposed to the herbicide coastal incident under climate
      change. It is of concern that society's response to every dimension of global
      climate change is mediated by culture. The Driver-Pressure-State-Impact-Response
      (DPSIR) cause-effect framework was applied in semi-structured interviews to
      explore coastal sensitivity and human adaptability. As a result, we indicated
      that despite the presence of two ethnic groups in the same place exposed to the
      incident they presented very different risk perceptions on both environmental
      degradation (ED) and adaptive capacity (AC) due to cultural values. We argued
      that the herbicide coastal incident involved people's risk perceptions and
      subsequently influenced their opinions and attitudes towards environmental
      problems. We concluded that the ethnic trait contributed to adaptive behaviors
      during environmental change. Culturally appropriate adaptations appeared to
      enhance risk perceptions and adaptation actions, suggesting a need for more
      rigorous cultural adaptation guidelines towards climate resilience when designing
      adaptation interventions for different ethnic groups.

PMID- 29059568
TI  - Regional analysis and derivation of copula-based drought Severity-Area-Frequency
      curve in Lake Urmia basin, Iran.
AB  - Droughts are extreme events characterized by temporal duration and spatial large
      scale effects. In general, regional droughts are affected by general circulation
      of the atmosphere (at large-scale) and regional natural factors, including the
      topography, natural lakes, the position relative to the center and the path of
      the ocean currents (at small-scale), and they don't cover the exact same effects
      in a wide area. Therefore, drought Severity-Area-Frequency (S-A-F) curve
      investigation is an essential task to develop decision making rule for regional
      drought management. This study developed the copula-based joint probability
      distribution of drought severity and percent of area under drought across the
      Lake Urmia basin, Iran. To do this end, one-month Standardized Precipitation
      Index (SPI) values during the 1971-2013 were applied across 24 rainfall stations
      in the study area. Then, seven copula functions of various families, including
      Clayton, Gumbel, Frank, Joe, Galambos, Plackett and Normal copulas, were used to
      model the joint probability distribution of drought severity and drought area.
      Using AIC, BIC and RMSE criteria, the Frank copula was selected as the most
      appropriate copula in order to develop the joint probability distribution of
      severity-percent of area under drought across the study area. Based on the Frank
      copula, the drought S-A-F curve for the study area was derived. The results
      indicated that severe/extreme drought and non-drought (wet) behaviors have
      affected the majority of study areas (Lake Urmia basin). However, the area
      covered by the specific semi-drought effects is limited and has been subject to
      significant variations.

PMID- 29059569
TI  - Analysis and modelling of surface Urban Heat Island in 20 Canadian cities under
      climate and land-cover change.
AB  - Surface Urban Heat Island (SUHI) is an urban climate phenomenon that is expected
      to respond to future climate and land-use land-cover change. It is important to
      further our understanding of physical mechanisms that govern SUHI phenomenon to
      enhance our ability to model future SUHI characteristics under changing
      geophysical conditions. In this study, SUHI phenomenon is quantified and modelled
      at 20 cities distributed across Canada. By analyzing MODerate Resolution Imaging
      Spectroradiometer (MODIS) sensed surface temperature at the cities over 2002
      2012, it is found that 16 out of 20 selected cities have experienced a positive
      SUHI phenomenon while 4 cities located in the prairies region and high elevation
      locations have experienced a negative SUHI phenomenon in the past. A
      statistically significant relationship between observed SUHI magnitude and city
      elevation is also recorded over the observational period. A Physical Scaling
      downscaling model is then validated and used to downscale future surface
      temperature projections from 3 GCMs and 2 extreme Representative Concentration
      Pathways in the urban and rural areas of the cities. Future changes in SUHI
      magnitudes between historical (2006-2015) and future timelines: 2030s (2026
      2035), 2050s (2046-2055), and 2090s (2091-2100) are estimated. Analysis of future
      projected changes indicate that 15 (13) out of 20 cities can be expected to
      experience increases in SUHI magnitudes in future under RCP 2.6 (RCP 8.5). A
      statistically significant relationship between projected future SUHI change and
      current size of the cities is also obtained. The study highlights the role of
      city properties (i.e. its size, elevation, and surrounding land-cover) towards
      shaping their current and future SUHI characteristics. The results from this
      analysis will help decision-makers to manage Canadian cities more efficiently
      under rapidly changing geophysical and demographical conditions.

PMID- 29059570
TI  - Mapping wildfire vulnerability in Mediterranean Europe. Testing a stepwise
      approach for operational purposes.
AB  - Vulnerability assessment is a vital component of wildfire management. This
      research focused on the development of a framework to measure and map
      vulnerability levels in several areas within Mediterranean Europe, where
      wildfires are a major concern. The framework followed a stepwise approach to
      evaluate its main components, expressed by exposure, sensitivity and coping
      capacity. Data on population density, fuel types, protected areas location, roads
      infrastructure and surveillance activities, among others, were integrated to
      create composite indices, representing each component and articulated in multiple
      dimensions. Maps were created for several test areas, in northwest Portugal,
      southwest Sardinia in Italy and northeast Corsica in France, with the
      contribution of local participants from civil protection institutions and forest
      services. Results showed the influence of fuel sensitivity levels, population
      distribution and protected areas coverage for the overall vulnerability classes.
      Reasonable levels of accuracy were found on the maps provided through the
      validation procedure, with an overall match above 72% for the several sites. The
      systematic and flexible approach applied allowed for adjustments to local
      circumstances with regards to data availability and fire management procedures,
      without compromising its consistency and with substantial operational
      capabilities. The results obtained and the positive feedback of end-users
      encourage its further application, as a means to improve wildfire management
      strategies at multiple levels with the latest scientific outputs.

PMID- 29059571
TI  - Associating potential 1,4-dioxane biodegradation activity with groundwater
      geochemical parameters at four different contaminated sites.
AB  - 1,4-Dioxane (dioxane) is a groundwater contaminant of emerging concern for which
      bioremediation may become a practical remediation strategy. Therefore, it is
      important to advance our heuristic understanding of geochemical parameters that
      are most influential on the potential success of intrinsic bioremediation of
      dioxane-impacted sites. Here, Pearson's and Spearman's correlation and linear
      regression analyses were conducted to discern associations between 1,4-dioxane
      biodegradation activity measured in aerobic microcosms and groundwater
      geochemical parameters at four different contaminated sites. Dissolved oxygen,
      which is known to limit dioxane biodegradation, was excluded as a limiting factor
      in this analysis. Biodegradation activity was positively associated with dioxane
      concentrations (p < 0.01; R < 0.70) as well as the number of catabolic thmA gene
      copies (p < 0.01; R = 0.80) encoding dioxane monooxygenase. Thus, whereas
      environmental factors such as pH, temperature, and nutrients may influence
      dioxane biodegradation, these parameters did not exert as strong of an influence
      on potential biodegradation activity as the in situ concentration of substrate
      dioxane at the time of sampling. This analysis infers that aerobic sites with
      higher dioxane concentrations are more likely to select and sustain a thriving
      population of dioxane degraders, while sites with relatively low dioxane
      concentrations would be more difficult to attenuate naturally and may require
      alternative remediation strategies.

PMID- 29059572
TI  - Evaluation of fire severity via analysis of photosynthetic pigments: Oak,
      eucalyptus and cork oak leaves in a Mediterranean forest.
AB  - Few studies to date have examined the effect of the high temperatures attained
      during wildfire events on the pigments present in forest foliage. Here, we seek
      to analyse the main photosynthetic pigments in the leaves of the oak, cork oak
      and eucalyptus following a wildfire. We also subject leaves of these last two
      species to a range of contact temperatures (100-500  degrees C) in the laboratory
      using a muffle furnace. The samples were left in the muffle for two hours at 100,
      150, 200, 250, 300, 350, 400 and 500  degrees C, in line with other soil study
      models (Ubeda et al., 2009; Dudaite et al., 2013). At temperatures above 250 
      degrees C, chromatography fails to detect any pigments. A minimal increase in
      temperature degrades chlorophyll, the process being more rapid in eucalyptus than
      in cork oak, while it increases pheophytin concentrations.

PMID- 29059573
TI  - Removal of high concentration of sulfate from pigment industry effluent by
      chemical precipitation using barium chloride: RSM and ANN modeling approach.
AB  - Sulfate ions pose a major threat and challenge in the treatment of industrial
      effluents. The sample of wastewater obtained from a pigment industry contained
      large quantities of sulfate in the form of sodium sulfate which resulted in high
      TDS. As the removal of sulfate from pigment industry effluent was not reported
      previously, this work was focused on removing the sulfate ions from the effluent
      by chemical precipitation using barium chloride. The efficiency of sulfate
      removal was nearly 100% at an excess dosage of barium chloride, which
      precipitates the dissolved sulfate ions in the form of barium sulfate.
      Optimization of the parameters was done using Response Surface Methodology (RSM).
      This work is the first attempt for modeling the removal of sulfate from pigment
      industry effluent using RSM and Artificial Neural Network (ANN). Prediction by
      both the models was evaluated and both of them exhibited good performance (R2
      value > 0.99). It was observed that the prediction by RSM (R2 value 0.9986) was
      closer to the experimental results than ANN prediction (R2 value 0.9955). The
      influence on the pH and conductivity of the solution by dosage of precipitant was
      also studied. The formation of barium sulfate was confirmed by characterization
      of the precipitate. Therefore, the sulfate removed from the effluent was
      converted into a commercially valuable precipitate.

PMID- 29059574
TI  - Synchronized methylene blue removal using Fenton-like reaction induced by
      phosphorous oxoanion and submerged plasma irradiation process.
AB  - In this study, a combination of phosphorus (PP) oxoanions in a submerged plasma
      irradiation (SPI) system was used to enhance the removal efficiency of dyes from
      wastewater. The SPI system showed synergistic methylene blue removal efficiency,
      due to the plasma irradiation and Fenton-like oxidation. The ferrous ions
      released from the iron electrode in the SPI system under plasmonic conditions
      form complexes with the PP anions, which can then react with dissolved oxygen
      (O2) or hydrogen peroxide (H2O2) via Fenton-like reactions. The experimental
      results revealed that a sodium triphosphate (TPP) combined SPI system has a
      higher dye removal efficiency than a tetrasodium pyrophosphate (DP) or a sodium
      hexametaphosphate (HMP) combined SPI system under similar dissolved iron ion
      concentrations. To confirm the accuracy of the proposed removal mechanism via
      Fenton-like oxidation, it was compared to SPI systems under an oxygen environment
      (TPP/SPI/O2 (k = 0.0182 s-1)) and a nitrogen environment (TPP/SPI/N2 (k = 0.0062
      s-1)). The results indicate that the hydroxyl radical (OH) in the TPP/SPI/O2
      system is the major oxidant in methylene blue removal, because the dye
      degradation rates dramatically decreased with the addition of radical scavengers
      such as tert-butanol (k = 0.0023 s-1) and methanol (k = 0.0021 s-1). On the other
      hand, no change was observed in the methylene blue removal efficiency of the
      TPP/SPI/O2 system when it was subjected to a wide range of pHs (3-9). In
      addition, it was proved that this system could be used to eliminate six different
      commercial dyes. The results of this study indicated that the TPP/SPI/O2 system
      is a promising advanced oxidation approach for dye wastewater treatment.

PMID- 29059575
TI  - Impact of energy taxation on economy, environmental and public health quality.
AB  - This paper argues computable general equilibrium model and assess impact of
      energy taxation on economy, environmental and public health quality in Tianjin.
      In order to investigate different energy taxation based on medical cost and labor
      loss, the computable general equilibrium model integrating with input-output
      table and social accounting matrix (SAM) was constructed. The medical expense
      caused by air pollution of Tianjin in 2007 is 396 million yuan and death for
      18104 people, which accounted for the total GDP and population 0.7540/00 and
      1.60/00, respectively. The results show that the enery taxes levy can improve the
      GDP, but it is only slightly. The energy taxes have adverse impact on energy
      sector because that the energy cost is increased. The scale of production is
      reduced, and the capital and labor resources are transferred to low energy
      consumption low emissions sector. The energy tax levy can reduce air pollutants
      concentration and improve air environmental quality. The PM10, SO2 and NO2
      concentration in the energy taxes 5%-30% was reduced by 0.24%-0.24%, 0.09-0.52%
      and 0.29%-0.52% respectively. The medical expense has little impact on GDP, but
      labor loss has a certain effect on GDP. For higher energy taxes rate, the health
      effects on GDP can reach 0.06%-0.16%. This simultaneous economic and
      environmental improvement and health effect would thus have positive implications
      regarding energy taxes of the country.

PMID- 29059576
TI  - Biodegradation of sulfamethoxazole in bacteria from three different origins.
AB  - Sulfamethoxazole (SMX) is a common medicine prescribed to treat infections. Due
      to vast use, SMX has been detected in different parts of the world. Hence, it has
      become a high risk because of its long term persistence with high biological
      activity in the ecosystem. Therefore, it is necessary to understand the mechanism
      of SMX degradation in different genus of bacteria, which is presently unclear. In
      the present study, degradation of 5 mg L-1 SMX was studied in three isolated pure
      bacterial cultures, Ochrobactrum sp. SMX-PM1-SA1, Labrys sp. SMX-W1-SC11 and
      Gordonia sp. SMX-W2-SCD14 and results showed up to 45.2%, 62.2% and 51.4%
      degradation, respectively within 288 h. Additionally, strain SA1 and strain SCD14
      showed up to 66.2% and 69.2% of 4-aminophenol degradation at an initial
      concentration of 5 mg L-1 within 216 h whereas Labrys sp. SMX-W1-SC11 completely
      degraded 4-aminophenol at the same concentration within 120 h. Moreover, all
      three pure bacteria also completely degraded 3-amino-5-methylisoxazole at initial
      concentration of 4 mg L-1 within 120 h. Furthermore, gas chromatography-mass
      spectrometry and quadrupole time-of-flight mass spectrometry analysis results
      revealed that 3-amino-5-methylisoxazole, 4-aminophenol and hydroquinone were the
      three main by-products of SMX catabolism. In addition, cell free extracts of both
      Labrys sp. SMX-W1-SC11 and Gordonia sp. SMX-W2-SCD14 showed hydroquinone
      dioxygenase activity. Besides, all three bacterial strains showed resistance to
      different heavy metals. Moreover, all three pure bacterial cultures also showed
      positive chemotactic response toward 3-amino-5-methylisoxazole and hydroquinone
      based on the drop plate assay. The results of this study recommend these
      microorganisms for bioremediation of SMX contaminated sites.

PMID- 29059577
TI  - Integrating developmental aspects in current thinking about personality
      pathology.
AB  - The current review outlines some recent highlights from the developmental
      literature on personality pathology with regard to its conceptualization,
      development, assessment and clinical utility. Notable parallels with adult
      evidence are described, but also unique and age-specific issues are discussed.
      Finally, suggestions for future research that may stimulate a life-span and
      integrative perspective on personality pathology from childhood onwards are
      proposed.

PMID- 29059578
TI  - Issues resolved and unresolved in pathological narcissism.
AB  - Narcissism is one of the oldest personality constructs, and yet debates about its
      definition and structure have been a topic of intense debate over the past
      decade. Recent independent reviews of the literature have proposed conceptually
      identical triarchic structural models of individual differences in pathological
      narcissism. In each model entitlement serves as the core of the construct, and
      its expression is moderated by basic personality/temperament to manifest in
      exhibitionism or vulnerability. However, the clinical observation that
      individuals high in pathological narcissism vacillate between grandiose and
      vulnerable states remains understudied and poorly understood. We review the
      recent research that has driven the contentious debates, emerging points of
      consensus, and necessary future directions for research.

PMID- 29059579
TI  - Metabolic solutions to the biosynthesis of some diaminomonocarboxylic acids in
      nature: Formation in cyanobacteria of the neurotoxins 3-N-methyl-2,3
      diaminopropanoic acid (BMAA) and 2,4-diaminobutanoic acid (2,4-DAB).
AB  - The non-encoded diaminomonocarboxylic acids, 3-N-methyl-2,3-diaminopropanoic acid
      (syn: alpha-amino-beta-methylaminopropionic acid, MeDAP; beta-N
      methylaminoalanine, BMAA) and 2,4-diaminobutanoic acid (2,4-DAB), are distributed
      widely in cyanobacterial species in free and bound forms. Both amino acids are
      neurotoxic in whole animal and cell-based bioassays. The biosynthetic pathway to
      2,4-DAB is well documented in bacteria and in one higher plant species, but has
      not been confirmed in cyanobacteria. The biosynthetic pathway to BMAA is unknown.
      This review considers possible metabolic routes, by analogy with reactions used
      in other species, by which these amino acids might be biosynthesised by
      cyanobacteria, which are a widespread potential environmental source of these
      neurotoxins. Where possible, the gene expression that might be implicated in
      these biosyntheses is discussed.

PMID- 29059580
TI  - Characteristics of peripheral blood NK and NKT-like cells in euthyroid and
      subclinical hypothyroid women with thyroid autoimmunity experiencing reproductive
      failure.
AB  - Thyroid autoimmunity (TAI) appears to play a crucial role in female infertility,
      recurrent pregnancy loss and IVF failure. Thyroid autoantibodies against thyroid
      peroxidase and thyroglobulin have been shown to represent an independent risk
      factor for infertility and miscarriage. Moreover, thyroxin hormone administration
      reduces the risk of obstetrical complications in TAI positive women. The aim of
      our present study was to investigate the immunological background of female
      infertility and recurrent pregnancy loss in euthyroid and subclinical hypothyroid
      women with TAI focusing on innate immunity. Phenotypic and functional analysis
      was carried out on peripheral blood mononuclear cells from healthy donors and TAI
      patients by flow cytometry. Our findings show Th1 oriented changes of innate
      immunity in the peripheral blood of women suffering from thyroid autoimmunity.
      Elevated NK and NKT-like cells ratios and enhanced natural cytotoxicity of TAI
      positive women reveal an altered immune status with possible negative impact on
      pregnancy outcome. It is important to notice that immune alterations are already
      established in the euthyroid phase of autoimmune thyroiditis before endocrine
      dysfunction develops and only the presence of thyroid autoantibodies indicate TAI
      condition. For this reason, screening of healthy women of reproductive age for
      the presence of thyroid autoantibodies would be beneficial not only from the
      endocrinological aspect but from the reproductive point of view since, although
      yet unexplained, thyroid hormone administration may improve pregnancy outcome.

PMID- 29059581
TI  - Direct PCR amplification of forensic touch and other challenging DNA samples: A
      review.
AB  - DNA evidence sample processing typically involves DNA extraction, quantification,
      and STR amplification; however, DNA loss can occur at both the DNA extraction and
      quantification steps, which is not ideal for forensic evidence containing low
      levels of DNA. Direct PCR amplification of forensic unknown samples has been
      suggested as a means to circumvent extraction and quantification, thereby
      retaining the DNA typically lost during those procedures. Direct PCR
      amplification is a method in which a sample is added directly to an amplification
      reaction without being subjected to prior DNA extraction, purification, or
      quantification. It allows for maximum quantities of DNA to be targeted, minimizes
      opportunities for error and contamination, and reduces the time and monetary
      resources required to process samples, although data analysis may take longer as
      the increased DNA detection sensitivity of direct PCR may lead to more instances
      of complex mixtures. ISO 17025 accredited laboratories have successfully
      implemented direct PCR for limited purposes (e.g., high-throughput databanking
      analysis), and recent studies indicate that direct PCR can be an effective method
      for processing low-yield evidence samples. Despite its benefits, direct PCR has
      yet to be widely implemented across laboratories for the processing of
      evidentiary items. While forensic DNA laboratories are always interested in new
      methods that will maximize the quantity and quality of genetic information
      obtained from evidentiary items, there is often a lag between the advent of
      useful methodologies and their integration into laboratories. Delayed
      implementation of direct PCR of evidentiary items can be attributed to a variety
      of factors, including regulatory guidelines that prevent laboratories from
      omitting the quantification step when processing forensic unknown samples, as is
      the case in the United States, and, more broadly, a reluctance to validate a
      technique that is not widely used for evidence samples. The advantages of direct
      PCR of forensic evidentiary samples justify a re-examination of the factors that
      have delayed widespread implementation of this method and of the evidence
      supporting its use. In this review, the current and potential future uses of
      direct PCR in forensic DNA laboratories are summarized.

PMID- 29059583
TI  - Darwin was right: where now for experimental evolution?
AB  - Over the last two decades interest in direct realisation of evolutionary process
      and the possibilities presented by real time evolution experiments with microbes
      have escalated. Long-term selection experiments with bacteria have made
      increasingly transparent the process of evolution by natural selection. In this
      short article we consider what next for the field and do so by highlighting two
      areas of interest: the genotype-to-phenotype map and the constraints it imposes
      on evolution, and studies on major evolutionary transitions and in particular the
      importance of selection working over more than one timescale. The latter we
      discuss in light of new technologies that allow imposition of Darwinian
      properties on populations and communities and how this allows exploration of new
      avenues of research. We conclude by commenting on microbial communities and the
      operation of evolutionary processes that are likely intrinsic-and specific-to
      communities.

PMID- 29059582
TI  - The effect of loss of O-antigen ligase on phagocytic susceptibility of motile and
      non-motile Pseudomonas aeruginosa.
AB  - The bacterial pathogen Pseudomonas aeruginosa undergoes adaptation and selection
      over the course of chronic respiratory tract infections which results in
      repeatedly-observed phenotypic changes that are proposed to enable its
      persistence. Two of the clinically significant P. aeruginosa phenotypic changes
      are loss of flagellar motility and modifications to LPS structure, including loss
      of O-antigen expression. The effect of loss of O-antigen, frequently described as
      conversion from smooth to rough LPS, and the combined effect of loss of motility
      and O-antigen on phagocytic susceptibility by immune cells remain unknown. To
      address this, we generated genetic deletion mutants of waaL, which encodes the O
      antigen ligase responsible for linking O-antigen to lipid A-core oligosaccharide,
      in both motile and non-motile P. aeruginosa strains. With the use of these
      bacterial strains we provide the first demonstration that, despite a progressive
      selection for P. aeruginosa with rough LPS during chronic pulmonary infections,
      loss of the LPS O-antigen does not confer phagocytic resistance in vitro.
      However, use of the waaLmotABmotCD mutant revealed that loss of motility confers
      resistance to phagocytosis regardless of the smooth or rough LPS phenotype. These
      findings reveal how the O-antigen of P. aeruginosa can influence bacterial
      clearance during infection and expand our current knowledge about the impact of
      bacterial phenotypic changes during chronic infection.

PMID- 29059584
TI  - Lactoferrin or ferrous salts for iron deficiency anemia in pregnancy: A meta
      analysis of randomized trials.
AB  - This systematic review and meta-analysis aimed to evaluate the efficacy of daily
      oral bovine lactoferrin versus daily oral ferrous iron preparations for treatment
      of iron deficiency anemia (IDA) during pregnancy. Searches were conducted on
      PubMed, ScienceDirect, ClinicalTrials.gov and CENTRAL databases from inception to
      February 2017 and the bibliographies of retrieved articles were screened. The
      PRISMA Statement was followed. Published English language randomized trials
      comparing lactoferrin with oral ferrous iron preparations in pregnant women with
      iron deficiency anemia were included. Quasi-randomized, non- randomized or
      studies including other known cause of anemia, gestational or pre-existent
      maternal diseases were excluded. Accordingly, 4 eligible trials (600 women) were
      analyzed. Primary outcome was change in hemoglobin level at 4 weeks of treatment.
      Secondary outcomes were; change in serum ferritin and iron, rates of
      gastrointestinal side effects, preterm birth, low birthweight, neonatal death and
      mean birthweight. Quality assessment was performed by the Cochrane risk of bias
      tool. Odds ratio and mean difference were used to integrate dichotomous and
      continuous outcomes respectively. Pooled estimates for change in hemoglobin
      levels at four weeks favored daily oral lactoferrin over daily oral ferrous
      sulphate (mean difference 0.77; 95% confidence interval [CI] 0.04-1.55; P=0.04, 4
      trials, 600 women). However, after subgroup analysis (degree of anemia), no
      significant difference in hemoglobin levels were found between both groups in
      mild anemia (mean difference 0.80; 95% CI -0.21 to 1.82, 3 trials, 372 women),
      but a significant increase favoring lactoferrin was reported in moderate anemia
      (mean difference 0.68; 95% CI 0.53-0.83; P<0.00001, one trial, 228 women).
      Significantly less gastrointestinal side effects were reported with lactoferrin
      treatment. No significant differences existed with regard to other outcomes. In
      conclusion, for pregnant women with IDA, daily oral bovine lactoferrin is just as
      good as ferrous sulfate in improving hematological parameters with fewer
      gastrointestinal side effects. Thereby, lactoferrin should be the iron
      replacement agent of choice for treatment of IDA in pregnancy.

PMID- 29059585
TI  - Cyclic and non-cyclic breast-pain: A systematic review on pain reduction, side
      effects, and quality of life for various treatments.
AB  - CYCLIC AND NON-CYCLIC BREAST-PAIN: A systematic review on pain reduction, side
      effects, and quality of life for various treatments. BACKGROUND: No clear
      systematic-review on all the various treatment regimen for (Non-) cyclical-breast
      pain currently exists. OBJECTIVES: The aim of this study was to assess the
      various forms of therapy for treatment of breast-pain and the evidence for their
      effectiveness. SEARCH STRATEGY: Search-terms included 'mastalgia' and 'therapy'
      or 'hormones' or 'nsaid' or 'psychotherapy' or 'analgesia' or 'surgery', and
      synonyms. SELECTION CRITERIA: The review was conducted according to the Preferred
      Reporting Items for Systematic-reviews and Meta-Analysis guidelines. RCT's and
      pro-/retrospective studies reporting on treatment of breast-pain were considered
      eligible. Minimal follow-up and sample-size criteria were 6 months and 10
      patients respectively. DATA COLLECTION AND ANALYSIS: Data was extracted using
      standardized tables and encompassed number of subjects, type of breast-pain and
      treatment, efficacy of treatment and clinical complications/side-effects. No
      pooling of data could be achieved due to heterogeneity amongst studies. MAIN
      RESULTS: Twenty-three studies were included, that reported on 2100 patients in
      total. Topical-Diclofenac was found to reduce pain by 58.7 and 63.3 on a Visual
      Analogue-Scale (VAS) in cyclical and non-cyclical-breast-pain respectively.
      Persistent cyclical-breast-pain can be treated with short courses (2-6 months) of
      either Bromocryptine (VAS?=25.4) or Danazol (VAS?=33.6) as long as benefits
      outweigh the side-effects. Last-resort options for unresponsive and severe
      debilitating breast-pain include surgery in the form of bilateral mastectomy with
      reconstruction. CONCLUSIONS: Pain reduction in patients with breast-pain can be
      achieved with analgesics, hormonal-regimen and possibly surgery as a last resort.
      Additional studies are needed with well-described patient-characteristics, robust
      study set-up, and longer follow-up times.

PMID- 29059586
TI  - An LC-MS/MS method for quantification of the active abiraterone metabolite
      Delta(4)-abiraterone (D4A) in human plasma.
AB  - Delta(4)-Abiraterone (D4A) is a recently discovered active metabolite of the oral
      anti-androgen drug abiraterone acetate. For quantification of this metabolite in
      human plasma, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      was developed and validated. Human plasma samples of patients treated with
      abiraterone acetate were prepared by protein precipitation with acetonitrile. The
      method was validated over a linear range of 0.2-20ng/mL. Intra-assay and inter
      assay variabilities were within +/-15% of the nominal concentrations for quality
      control (QC) samples at medium and high concentrations and within +/-20% at the
      lower limit of quantification (LLOQ), respectively. The described method for
      quantification of D4A was validated successfully and implemented to support
      therapeutic drug monitoring in patients treated with abiraterone acetate.

PMID- 29059587
TI  - A high-throughput UHPLC method for the analysis of 5-nitroimidazole residues in
      milk based on salting-out assisted liquid-liquid extraction.
AB  - A novel salting-out assisted liquid-liquid extraction (SALLE) method has been
      developed for the extraction of eight 5-NDZ antibiotics from milk samples prior
      to their analysis by UHPLC. An exhaustive study of the parameters involved in the
      SALLE procedure has been carried out, optimizing the extraction solvent volume,
      the amount of the salt agent, and the centrifugation and vortex timing by an
      experimental design. After sample treatment, the obtained extract was
      reconstituted in the mobile phase (6:94 (v/v) acetonitrile/water containing 0.1%
      (v/v) of formic acid) and analyzed by the proposed UHPLC-UV method. Separation
      was accomplished in a C18 Zorbax Eclipse Plus (50mm*2.1mm, 1.8MUm) column at 45
      degrees C within 8min. Gradient mode was considered using a mobile phase
      consisting of 0.1% (v/v) formic acid aqueous solution and acetonitrile containing
      0.1% (v/v) formic acid at a flow rate of 0.45mL/min. Analytical signals were
      monitored at 320nm. Matrix-matched calibration curves showed satisfactory
      linearity (R2>=0.996). LODs, ranging from 2 to 4MUg/L, were achieved and
      precision studies showed RSDs lower than 12.8% in terms of peak height.
      Additionally, recoveries higher than 62.8% were obtained for all studied
      compounds in milk samples.

PMID- 29059588
TI  - Enablement of the direct analysis of excipients in monoclonal antibody
      formulations through the incorporation of a wide pore C18 protein trap with
      hydrophilic interaction liquid chromatography.
AB  - Establishing and maintaining the correct formulation composition is essential for
      ensuring the stability of biopharmaceutical drug products. A barrier to the
      routine assessment of excipient concentration is the lack of convenient and
      robust methods for the direct analysis of solutions containing high protein
      concentrations. To address this need an HPLC method was developed utilizing a
      wide-pore C18 guard column to trap proteins in-line with a hydrophilic
      interaction liquid chromatographic column to separate excipients. This method
      allows for a simple and direct analysis of excipients such as amino acids,
      carboxylic acids, simple carbohydrates, and inorganic ions across multiple drug
      formulations and process streams containing different therapeutic antibodies. The
      method was successfully validated for specificity, precision, accuracy,
      linearity, and robustness.

PMID- 29059589
TI  - High-frequency burst vagal nerve simulation therapy in a natural primate model of
      genetic generalized epilepsy.
AB  - PURPOSE: Since the approval of Vagal Nerve Stimulation (VNS) Therapy for
      medically refractory focal epilepsies in 1997, it has been also reported to be
      effective for a wide range of generalized seizures types and epilepsy syndromes.
      Instead of conventional VNS Therapy delivered at 20-30Hz signal frequencies, this
      study evaluates efficacy and tolerability of high-frequency burst VNS in a
      natural animal model for genetic generalized epilepsy (GGE), the epileptic
      baboon. METHODS: Two female baboons (B1 P.h. Hamadryas and B2 P.h. Anubis x
      Cynocephalus) were selected because of frequently witnessed generalized tonic
      clonic seizures (GTCS) for VNS implantation. High-frequency burst VNS Therapy was
      initiated after a 4-5 week baseline; different VNS settings (0.25, 2 or 2.5mA,
      300Hz, 4 vs 7 pulses, 0.5-2.5s interburst interval, and intermittent stimulation
      for 1-2 vs for 24h per day) were tested over the subsequent 19 weeks, which
      included a 4-6 week wash-out period. GTCS frequencies were quantified for each
      setting, while seizure duration and postictal recovery times were compared to
      baseline. Scalp EEG studies were performed at almost every setting, including
      intermittent light stimulation (ILS) to evaluate photosensitivity. Pre-ILS ictal
      and interictal discharge rates, as well as ILS responses were compared between
      trials. The Novel Object test was used to assess potential treatment effects on
      behavior. RESULTS: High-frequency burst VNS Therapy reduced GTCS frequencies at
      all treatment settings in both baboons, except when output currents were reduced
      (0.25mA) or intermittent stimulation was restricted (to 1-2h/day). Seizure
      duration and postictal recovery times were unchanged. Scalp EEG studies did not
      demonstrate treatment-related decrease of ictal or interictal epileptic
      discharges or photosensitivity, but continuous treatment for 120-180s during ILS
      appeared to reduce photoparoxysmal responses. High-frequency burst VNS Therapy
      was well-tolerated by both baboons, without cardiac or behavioral changes.
      Repetitive muscle contractions involving the neck and left shoulder girdle were
      observed intermittently, most commonly at 0.5 interburst intervals, but these
      were transient, resolving with a few cycles of stimulation and not noted in
      wakefulness. CONCLUSIONS: This preclinical pilot study demonstrates efficacy and
      tolerability of high-frequency burst VNS Therapy in the baboon model of GGE. The
      muscle contractions may be due to aberrant propagation of the stimulus along the
      vagal nerve or to the ansa cervicalis, but can be reduced by minimal adjustment
      of current output or stimulus duration.

PMID- 29059590
TI  - Quality assessment for wireless capsule endoscopy videos compressed via HEVC:
      From diagnostic quality to visual perception.
AB  - Maintaining the quality of medical images and videos is an essential part of the
      e-services provided by the healthcare sector. The convergence of modern
      communication systems and the healthcare industry necessitates the provision of
      better quality of service and experience by the service provider. Recent
      inclusion and standardization of the high efficiency video coder (HEVC) has made
      it possible for medical data to be compressed and transmitted over wireless
      networks with minimal compromise of the quality. Quality evaluation and
      assessment of these medical videos transmitted over wireless networks is another
      important research area that requires further exploration and attention. In this
      paper, we have conducted an in-depth study of video quality assessment for
      compressed wireless capsule endoscopy (WCE) videos. Our study includes the
      performance evaluation of several state-of-the-art objective video quality
      metrics in terms of determining the quality of compressed WCE videos. Subjective
      video quality experiments were conducted with the assistance of experts and non
      experts in order to predict the diagnostic and visual quality of these medical
      videos, respectively. The evaluation of the metrics is based on three major
      performance metrics that include, correlation between the subjective and
      objective scores, relative statistical performance and computation time. Results
      show that the metrics information fidelity criterion (IFC), visual information
      fidelity-(VIF) and especially pixel based VIF stand out as best performing
      metrics. Furthermore, our paper reports the performance of HEVC compression on
      medical videos and according to the results, it performs optimally in preserving
      the diagnostic and visual quality of WCE videos at Quantization Parameter (QP)
      values of up to 35 and 37 respectively.

PMID- 29059591
TI  - Features based on the percolation theory for quantification of non-Hodgkin
      lymphomas.
AB  - Non-Hodgkin lymphomas are a health problem that affects over 70,000 people per
      year in the United States alone. The early diagnosis and the identification of
      this lymphoma are essential for an effective treatment. The classification of non
      Hodgkin lymphomas is a task that continues to rank as one of the main challenges
      faced by hematologists, pathologists, as well as in the producing of computer
      vision methods due to its inherent complexity. In this paper, we present a new
      method to quantify and classify tissue samples of non-Hodgkin lymphomas based on
      the percolation theory. The method consists of associating multiscale and
      multidimensional approaches in order to divide the image into smaller regions and
      then verifying color similarity between pixels. A cluster labeling algorithm was
      applied to each region of interest to obtain the values for the number of
      clusters, occurrence of percolation and coverage ratio of the largest cluster.
      The method was tested on different classifiers aiming to differentiate three
      different groups of non-Hodgkin lymphomas. The obtained results (AUC rates
      between 0.940 and 0.993) were compared to those provided by methods consolidated
      in the Literature, which indicates that the percolation theory is a suitable
      approach for identifying these three classes of non-Hodgkin lymphomas, those
      being: mantle cell lymphoma, follicular lymphoma and chronic lymphocytic
      leukemia.

PMID- 29059592
TI  - Classification of the trabecular bone structure of osteoporotic patients using
      machine vision.
AB  - Osteoporosis is a common bone disease which often leads to fractures. Clinically,
      the major challenge for the automatic diagnosis of osteoporosis is the complex
      architecture of bones. The clinical diagnosis of osteoporosis is conventionally
      done using Dual-energy X-ray Absorptiometry (DXA). This method has specific
      limitations, however, such as the large size of the instrument, a relatively high
      cost and limited availability. The method proposed here is based on the automatic
      processing of X-ray images. The bone X-ray image was statistically processed and
      strategically reformed to extract discriminatory statistical features of
      different orders. These features were used for machine learning for the
      classification of two populations composed of osteoporotic and healthy subjects.
      Four classifiers - support vector machine (SVM), k-nearest neighbors, Naive Bayes
      and artificial neural network - were used to test the performance of the proposed
      method. Tests were performed on X-ray images of the calcaneus bone collected from
      the hospital of Orleans. The results are significant in terms of accuracy and
      time complexity. Experimental results indicate a classification rate of 98% using
      an SVM classifier which is encouraging for automatic osteoporosis diagnosis using
      bone X-ray images. The low time complexity of the proposed method makes it
      suitable for real time applications.

PMID- 29059594
TI  - The age-related slow increase in amyloid pathology in APP.V717I mice activates
      microglia, but does not alter hippocampal neurogenesis.
AB  - In Alzheimer's disease, the hippocampus is characterized by abundant deposition
      of amyloid peptides (amyloid beta [Abeta]) and neuroinflammation. Adult
      hippocampal neurogenesis (AHN) is a form of plasticity that contributes to
      cognition and can be influenced by either or both pathology and
      neuroinflammation. Their interaction has been studied before in rapidly
      progressing transgenic mouse models with strong overexpression of amyloid
      precursor protein (APP) and/or presenilin 1. So far, changes in AHN and
      neuroinflammation remain poorly characterized in slower progressing models at
      advanced age, which approach more closely sporadic Alzheimer's disease. Here, we
      analyzed 10- to 26-month-old APP.V717I mice for possible correlations between
      Abeta pathology, microglia, and AHN. The age-related increase in amyloid
      pathology was closely paralleled by microglial CD68 upregulation, which was
      largely absent in age-matched wild-type littermates. Notably, aging reduced the
      AHN marker doublecortin, but not calretinin, to a similar extent in wild-type and
      APP.V717I mice between 10 and 26 months. This demonstrates that AHN is influenced
      by advanced age in the APP.V717I mouse model, but not by Abeta and microglial
      activation.

PMID- 29059593
TI  - Splenectomy protects aged mice from injury after experimental stroke.
AB  - Elderly stroke patients and aged animals subjected to experimental stroke have
      significantly worse functional recovery and higher mortality compared to younger
      subjects. Activation of the peripheral immune system is known to influence stroke
      outcome. Prior studies have shown that splenectomy reduces ischemic brain injury
      in young mice. As immune function changes with aging, it is unclear whether
      splenectomy will confer similar benefits in aged animals. We investigated the
      contribution of spleen to brain injury after cerebral ischemia in aged male mice.
      Splenic architecture and immune cell composition were altered in aged mice.
      Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and
      infarct outcomes in aged male mice. In addition, there was a reduction in
      peripheral immune cell infiltration into the brain and decreased levels of
      peripheral inflammatory cytokines after stroke in aged splenectomized mice.
      Splenectomy immediately after reperfusion also improved behavioral and infarct
      outcomes. This study suggests that inhibition of the splenic immune response is a
      translationally relevant target to pursue for stroke treatment in aged
      individuals.

PMID- 29059595
TI  - White-matter microstructure and hearing acuity in older adults: a population
      based cross-sectional DTI study.
AB  - To study the relation between the microstructure of white matter in the brain and
      hearing function in older adults we carried out a population-based, cross
      sectional study. In 2562 participants of the Rotterdam Study, we conducted
      diffusion tensor imaging to determine the microstructure of the white-matter
      tracts. We performed pure-tone audiogram and digit-in-noise tests to quantify
      hearing acuity. Poorer white-matter microstructure, especially in the association
      tracts, was related to poorer hearing acuity. After differentiating the separate
      white-matter tracts in the left and right hemisphere, poorer white-matter
      microstructure in the right superior longitudinal fasciculus and the right
      uncinate fasciculus remained significantly associated with worse hearing. These
      associations did not significantly differ between middle-aged (51-69 years old)
      and older (70-100 years old) participants. Progressing age was thus not found to
      be an effect modifier. In a voxel-based analysis no voxels in the white matter
      were significantly associated with hearing impairment.

PMID- 29059596
TI  - Association of postoperative delirium with markers of neurodegeneration and brain
      amyloidosis: a pilot study.
AB  - The aim of the study was to investigate the association between postoperative
      delirium (POD) and in vivo markers of Alzheimer's disease pathology in
      nondemented hip fracture surgery patients. POD was assessed with the Confusion
      Assessment Method. Amyloid load was quantified on 18F-Flutemetamol positron
      emission tomography images as standardized uptake value ratio. Secondary outcome
      measures were gray matter volumes, white matter integrity, and functional
      connectivity at rest. All the patients with POD (POD+, N = 5) were amyloid
      negative (standardized uptake value ratio <0.59), whereas 6 out of 11 patients
      without POD (POD-) showed brain amyloid positivity. POD+ compared to POD-
      displayed: lower gray matter volumes in the amygdala (p = 0.003), in the middle
      temporal gyrus and in the anterior cingulate cortex (p < 0.001), increased
      diffusivity in the genu of the corpus callosum and in the anterior corona radiata
      (p < 0.05), and higher functional connectivity within the default mode network (p
      < 0.001). POD patients showed altered gray and white matter integrity in the
      fronto-limbic regions in absence of brain amyloidosis. Based on this preliminary
      investigation, delirium pathophysiology might be independent of Alzheimer's
      disease. Future studies on larger samples are needed to confirm this hypothesis.

PMID- 29059597
TI  - Justification and authority in institutional review board decision letters.
AB  - While ethnographic study has described the discussions that occur during human
      subjects research ethics review, investigators have minimal access to the
      interactions of ethics oversight committees. They instead receive letters
      stipulating changes to their proposed studies. Ethics committee letters are
      central to the practice of research ethics: they change the nature of research,
      alter the knowledge it produces, and in doing so construct what ethical research
      is and how it is pursued. However, these letters have rarely been objects of
      analysis. Accordingly, we conducted a qualitative analysis of letters written by
      American institutional review boards (IRBs) overseeing biomedical and health
      behavioral research. We sought to clarify how IRBs exercise their authority by
      assessing the frequency with which they provided reasons for their stipulations
      as well as the nature of these reasons. We found that IRBs frequently do not
      justify their stipulations; rather, they often leave ethical or regulatory
      concerns implicit or frame their comments as boilerplate language replacements,
      procedural instructions, or demands for missing information. When they do provide
      justifications, their rationales exhibit substantial variability in explicitness
      and clarity. These rhetorical tendencies indicate that the authority of IRBs is
      grounded primarily in their role as bureaucratic gatekeepers. We conclude by
      suggesting that greater attention to justification could help shift the basis of
      the IRB-researcher relationship from compliance to mutual accountability.

PMID- 29059598
TI  - Assessment of biochemical mechanisms of tolerance to chlorpyrifos in ancient and
      contemporary Daphnia pulicaria genotypes.
AB  - The evolution of tolerance to environmental contaminants in non-target taxa has
      been largely studied by comparing extant populations experiencing contrasting
      exposure. Previous research has demonstrated that "resurrected" genotypes from a
      population of Daphnia pulicaria express temporal variation in sensitivity to the
      insecticide chlorpyrifos. Ancient genotypes (1301-1646AD.) were on average more
      sensitive to this chemical compared to the contemporary genotypes (1967-1977AD.).
      To determine the physiological mechanisms of tolerance, a series of biochemical
      assays was performed on three ancient and three contemporary genotypes; these six
      genotypes exhibited the most sensitive and most tolerant phenotypes within the
      population, respectively. Metabolic tolerance mechanisms were evaluated using
      acute toxicity testing, while target-site tolerance was assessed via in vitro
      acetylcholinesterase (AChE) assays. Acute toxicity tests were conducted using i)
      the toxic metabolite chlorpyrifos-oxon (CPF-oxon) and ii) CPF-oxon co-applied
      with piperonyl butoxide (PBO), a known Phase-I metabolic inhibitor. Both series
      of toxicity tests reduced the mean variation in sensitivity between tolerant and
      sensitive genotypes. Exposure to CPF-O reduced the disparity from a 4.7-fold to
      1.6-fold difference in sensitivity. The addition of PBO further reduced the
      variation to a 1.2-fold difference in sensitivity. In vitro acetylcholinesterase
      assays yielded no significant differences in constitutive activity or target-site
      sensitivity. These findings suggest that pathways involving Phase-I
      detoxification and/or bioactivation of chlorpyrifos play a significant role in
      dictating the microevolutionary trajectories of tolerance in this population.

PMID- 29059599
TI  - A comparison of progesterone assays for determination of peripheral pregnane
      concentrations in the late pregnant mare.
AB  - During the latter half of gestation in mares, there is a complex milieu of
      pregnanes in peripheral blood. Progesterone concentrations are often assessed by
      immunoassay during late gestation as a measure of pregnancy well-being; however,
      interpretation of results is complicated by the numerous cross-reacting pregnanes
      present in high concentrations during late gestation. Further, many mares are
      supplemented with an exogenous progestin, altrenogest, which may also cross-react
      with existing assays and further confound interpretation. The objectives of this
      study were: 1) to compare differences in pregnane concentrations determined with
      four immunoassays compared to LC-MS/MS and 2) to assess cross-reactivity observed
      with the same immunoassays, specifically considering pregnenolone (P5),
      progesterone (P4), 5alpha-dihydroprogesterone (DHP), allopregnanolone, and
      altrenogest. Blood samples from four healthy mares in late gestation were
      evaluated by immunoassay and by LC-MS/MS. Measured immuno-reactive progesterone
      (ir-progesterone) concentrations differed (p < 0.0001) between immunoassays,
      although results were highly correlated (r = 0.85-1.0; p < 0.001). Measured ir
      progesterone concentrations by immunoassay were linearly associated (r2 = 0.68
      0.76; p < 0.001) with concentrations of P5, P4, DHP, and allopregnanolone
      determined by LC-MS/MS. There was no detectable cross-reaction of altrenogest in
      any immunoassay, but varying degrees of cross-reactivity was observed with other
      pregnanes analyzed. These data confirm ir-progesterone concentrations during late
      gestation vary depending upon the assay used and the cross-reactivity to other
      pregnanes present in late gestation, although the synthetic progestin altrenogest
      did not affect the results of any immunoassay tested.

PMID- 29059600
TI  - 17alpha-Methyltestosterone implants accelerate spermatogenesis in common snook,
      Centropomus undecimalis, during first sexual maturation.
AB  - The common snook, Centropomus undecimalis, is an emerging species for intensive
      fish culture, however, some reproductive aspects of this species, especially the
      development of the testes and the action of androgen hormones on spermatogenesis
      have not been studied. The objective of this study was to evaluate the effects of
      17alpha-methyltestosterone (MT) on spermatogenesis and steroidogenesis during the
      first sexual maturation of the common snook. The fish, which were reproduced in
      captivity, had a body weight of 305.80 +/- 35.60 g and a total length of 34,11 +/
      1,08 cm. We used ethylene-vinyl-acetate (EVAc) implants with four concentrations
      of the hormone MT: T1 (0.3 mg/kg); T2 (3.0 mg/kg); T3 (15.0 mg/kg) and T4 (30.0
      mg/kg), and a control group that did not receive the hormone. The gonads
      increased (P < 0.05) in relation to the concentrations of MT. Histological
      analysis revealed a progression of spermatogenesis in the MT treatments,
      especially in T3 and T4. Sperm release was attained in some fish treated with MT.
      However, there was a partial suppression of the levels of testosterone (T) and 11
      ketotestosterone (11-KT) in plasma in the MT treatments, indicating a negative
      feedback on steroidogenesis. However, this suppression of T and 11-KT in plasma
      did not prevent an increase in the gonadosomatic index and the progression of
      gametogenesis. There was also an increase of estradiol (E2) in plasma in the
      treatments with the highest MT concentrations. The results suggest that the
      application of EVAc implants with MT at concentrations of 15 and 30 mg/kg
      stimulates the development and growth of the testes and accelerates
      spermatogenesis.

PMID- 29059601
TI  - Effects of pregnancy and short-lasting acute feed restriction on total ghrelin
      concentration and metabolic parameters in dairy cattle.
AB  - The aims of this study were: to compare total ghrelin concentration throughout
      pregnancy between lactating cows and heifers, and to study the response to acute
      feed restriction in pregnant or non-pregnant heifers. Blood samples were
      collected each month of pregnancy from cows (n = 5) and heifers (n = 5) and
      analyzed for total ghrelin concentration. Compared to pre-conception values,
      ghrelin concentrations tended to be greater during 3rd month of pregnancy in
      heifers, whereas they were higher in the 7th, 8th and 9th months in lactating
      cows, but no difference was detected between lactating cows and heifers. In
      experiment two, pregnant (n = 4) and non-pregnant (n = 4) heifers were fasted for
      24 h. Blood samples were collected 0, 4, 8, 12, 16 and 24 h of fasting and were
      assayed for, insulin, glucose, cortisol, BHBA and NEFA concentrations, and at
      time points 0, 8, 16 and 24 for total ghrelin determination. Compared to satiety,
      ghrelin concentrations were higher at 8th, 16th and 24th hour of fasting in
      pregnant and at 8th hour in non-pregnant animals, but no difference was detected
      between pregnant and non-pregnant heifers. Pregnant heifers had lower glucose
      concentrations than non-pregnant ones. Insulin concentrations were reduced at 4
      and 8 h of fasting in pregnant heifers, and stayed unaffected in non-pregnant
      ones. Cortisol concentrations increased after 4th hour and remained elevated
      throughout the sampling period in pregnant heifers, while they increased at 24th
      h in non-pregnant animals. Here, we provide evidence that total ghrelin
      concentrations rise in response to feed restriction. Albeit no group effect was
      evident, our results imply that a) during the last trimester of pregnancy total
      ghrelin is secreted in different pattern between lactating cows and heifers, b)
      pregnant animals are more responsive than non-pregnant ones to hunger induced
      stress.

PMID- 29059602
TI  - Superovulatory response following FSH, eCG-FSH and hMG and pregnancy rates
      following transfer of hatched blastocyst embryos with different diameter and
      shape in dromedary camel.
AB  - The objectives of this study were to compare three superovulation protocols and
      to investigate the effect of embryo diameter and shape on pregnancy rates in
      dromedary camel. In Experiment 1, following follicular wave synchronization of
      donors using two injections of GnRH (25 MUg, im), superovulation was initiated 2
      days after the second GnRH (Day 0 of experiment). Then, donors were assigned into
      three groups (n = 5) and received 1) FSH alone (390 mg), 2) eCG (1000 IU; single
      dose on Day 0) and FSH (330 mg) and 3) hMG (17.5 ampules). FSH and hMG were
      administered twice daily, in decreasing doses, for 5.5 days. Thirty-six hours
      after the last dose of FSH or hMG, donors were mated once. On Day 4 of
      superovulation, the diameter and number of follicles and on Day 7.5 after mating,
      total number of corpora lutea and follicles >=9 mm were recorded using ultrasound
      examination. On Day 8.5 after mating, embryos were recovered non-surgically. In
      Experiment 2, on Day 6.5 after inducing ovulation, recipients (n = 139) received
      a single 7.5 days old hatched blastocyst. The diameter and shape (round, oval,
      collapsed) of transferred embryos were recorded. Pregnancy was detected on Day 25
      after embryo transfer. Data were analyzed using Proc GLM, Proc FREG, Proc CORR
      and Proc Genmod of SAS. The number of corpora lutea was greater in FSH (22.4 +/-
      2.25) than eCG-FSH (11.6 +/- 2.58) and hMG (7 +/- 3.19; P < 0.01). Total number
      of embryos was higher in FSH (16.2 +/- 2.72) than hMG (1.6 +/- 1.17; P < 0.01).
      In FSH group, there was correlation between the ratio of follicles >6
      mm/follicles <=6 mm on Day 4 of superovulation and total number of corpora lutea
      (r = 0.9; P < 0.05) and embryos (r = 0.91; P < 0.05). In the latter group, there
      was also correlation between corpora lutea and number of embryos (r = 0.92; P <
      0.05). Transfer of embryos collected from different superovulation protocols did
      not affect pregnancy rates (P > 0.05). The diameter of hatched blastocysts had
      significant effect on pregnancy rates (P < 0.05). Medium size embryos (601-985
      MUm) produced greater pregnancy rates (50.8%) compared to small (275-600 MUm;
      25%) and large (986-1571 MUm; 32%) embryos (P < 0.05). In conclusion, FSH
      protocol provided better and predictable superovulatory response. Greater
      pregnancy rates could be achieved by transferring medium size hatched blastocysts
      in dromedary camel.

PMID- 29059603
TI  - Suitability of the hemi-zona assay for the evaluation of the effect of the length
      of the equilibration period before cryopreservation.
AB  - The aim of this study was to test the suitability of the interspecific hemizona
      assay (HZA) to predict the fertilizing capacity of bovine sperm after modifying
      the length of the equilibration period before freezing and thawing. Ejaculates
      from 10 proven fertile bulls were split after dilution, equilibrated at 4 
      degrees C for either 24 h (control sperm = CS) or 6, 48, 72 or 96 h (test sperm =
      TS) and cryopreserved. Hemizona (HZ) pairs from in vitro matured pig oocytes were
      used for the heterologous HZA: After thawing and swim-up (1 h) CS and TS were co
      incubated with matching HZ (125,000 S/HZ in 25 MUL Fert-TALP) for 4 h.
      Spermatological analyses (progressive motile sperm (PMS), plasma membrane- and
      acrosome-intact sperm (PMAI), sperm showing a high degree of DNA fragmentation
      (%DFI)) were performed after 0 and 3 h of incubation after thawing. After an
      equilibration time of 48 h and 72 h values for PMAI0h were higher (P < 0.05)
      compared to PMAI0h values of sperm equilibrated for 6 h, and %DFI3h values were
      higher after 96 h (P < 0.05) compared to 6 h equilibration. Between 12 and 90 TS
      and 13-97 CS were tightly bound to each HZ, respectively. The mean Hemizona Index
      (HZI) after a sperm equilibration for 48 h (HZI = 92.3 +/- 12.7) or 72 h (HZI =
      98.9 +/- 16.23) was higher (P < 0.01) than after an equilibration for 6 h (HZI =
      73.3 +/- 13.93) or 96 h (HZI = 81.3 +/- 11.41). The HZI for 96 h equilibration
      was moderately negatively related to PMS0h and PMS3h (r < -0.35, P < 0.05).
      Furthermore the HZI for 6 h equilibration was highly negatively correlated with
      DFI0h (r = -0,46, P < 0.01). On the basis of these results it can be concluded
      that the hemi-zona assay is a suitable test to detect alterations in the
      fertilizing capacity of bovine sperm after modifying the equilibration period.

PMID- 29059604
TI  - The imbalance between C and N metabolism during high nitrate supply inhibits
      photosynthesis and overall growth in maize (Zea mays L.).
AB  - Nitrogen (N) is an important regulator of photosynthetic carbon (C) flow in
      plants, and an adequate balance between N and C metabolism is needed for correct
      plant development. However, an excessive N supply can alter this balance and
      cause changes in specific organic compounds associated with primary and secondary
      metabolism, including plant growth regulators. In previous work, we observed that
      high nitrate supply (15 mM) to maize plants led to a decrease in leaf expansion
      and overall biomass production, when compared with low nitrate supply (5 mM).
      Thus, the aim of this work is to study how overdoses of nitrate can affect
      photosynthesis and plant development. The results show that high nitrate doses
      greatly increased amino acid production, which led to a decrease in the
      concentration of 2-oxoglutarate, the main source of C skeletons for N
      assimilation. The concentration of 1-aminocyclopropane-1-carboxylic acid (and
      possibly its product, ethylene) also rose in high nitrate plants, leading to a
      decrease in leaf expansion, reducing the demand for photoassimilates by the
      growing tissues and causing the accumulation of sugars in source leaves. This
      accumulation of sugars, together with the decrease in 2-oxoglutarate levels and
      the reduction in chlorophyll concentration, decreased plant photosynthetic rates.
      This work provides new insights into how high nitrate concentration alters the
      balance between C and N metabolism, reducing photosynthetic rates and disrupting
      whole plant development. These findings are particularly relevant since negative
      effects of nitrate in contexts other than root growth have rarely been studied.

PMID- 29059605
TI  - The interplay between sharing behavior and beliefs about others in children
      during dictator games.
AB  - Previous studies in adults demonstrated that beliefs and sharing decisions in
      social scenarios are closely related. However, to date, little is known about the
      development of this relationship in children. By using a modified dictator game,
      we assessed sharing behavior and beliefs about others in children between 3 and
      12 years old. We performed four studies (N = 376) aimed to assess whether
      decisions were related to beliefs (Studies 1 and 2) and whether information about
      the recipient's forced sharing behavior would shape decisions and beliefs
      (Studies 3 and 4). Results of Studies 1 and 2 showed that beliefs about others'
      generosity were related to children's sharing behavior. In Studies 3 and 4, we
      found that only children older than 9 years shared more pieces of candy when they
      knew that the recipient would be forced to share (cooperative context) than when
      they knew that the recipient would be forced not to share (noncooperative
      context). Besides, children older than 6 years did not modify their beliefs about
      others' generosity according to these social contexts. These results suggest that
      normative or preconceived beliefs about the functioning of the social world may
      guide social behavior in children.

PMID- 29059607
TI  - Dynamic pathway regulation: recent advances and methods of construction.
AB  - Microbial cell factories are a renewable source for the production of biofuels
      and valuable chemicals. Dynamic pathway regulation has proved successful in
      improving production of molecules by balancing flux between growth of cells and
      production of metabolites. Systems for autonomous induction of pathway regulation
      are increasingly being developed, which include metabolite responsive promoters,
      biosensors, and quorum sensing systems. Since engineering such systems are
      dependent on the available methods for controlling protein abundance in the
      desired host, we review recent tools used for gene repression at the
      transcriptional, post-transcriptional and post-translational levels in
      Escherichia coli and Saccharomyces cerevisiae. These approaches may facilitate
      pathway engineering for biofuel and biochemical production.

PMID- 29059606
TI  - Mutations in RNA methylating enzymes in disease.
AB  - RNA methylation is an abundant modification identified in various RNA species in
      both prokaryotic and eukaryotic organisms. However, the functional roles for the
      majority of these methylations remain largely unclear. In eukaryotes, many RNA
      methylations have been suggested to participate in fundamental cellular
      processes. Mutations in eukaryotic RNA methylating enzymes, and a consequent
      change in methylation, can lead to the development of diseases and disorders. In
      contrast, loss of RNA methylation in prokaryotes can be beneficial to
      microorganisms, especially under antibiotic pressure. Here we discuss several
      recent advances in understanding mutational landscape of both eukaryotic and
      prokaryotic RNA methylating enzymes and their relevance to disease and antibiotic
      resistance.

PMID- 29059608
TI  - Use of biologic mesh at ostomy takedown to prevent incisional hernia: A case
      series.
AB  - INTRODUCTION: Incisional hernias are a relatively common occurrence after ostomy
      takedown with a incidence of 30-35%. The use of biologic mesh offers a means to
      bolster the stoma incision site with a lower risk of infection than synthetic
      mesh. METHODS: This study represents a retrospective chart review of six patients
      who underwent stoma takedown and had biologic mesh placed in the retrorectus
      position during repair from March 2015 until March 2016. RESULTS: There has been
      a zero-rate of hernia occurrence for the six patients who underwent stoma
      takedown. No incisional hernias were noted on physical exam with follow up
      ranging from 11 to 25 months. CONCLUSION: We conclude that placement of biologic
      mesh is a safe and effective way of preventing incisional hernias at stoma sites.

PMID- 29059609
TI  - A case of laparoscopy-assisted vaginal cuff suturing for vaginal cuff dehiscence
      after total laparoscopic hysterectomy.
AB  - INTRODUCTION: Vaginal cuff dehiscence after hysterectomy is a rare complication
      and occurs in less than 1% of patients. It can present with serious
      complications, such as bowel evisceration and peritonitis. PRESENTATION OF CASE:
      A 51-year-old multigravida Korean woman underwent total laparoscopic hysterectomy
      for leiomyoma. Six months later, she reported lower abdominal pain and vaginal
      bleeding. Physical examination revealed rebound tenderness in the lower abdomen,
      and pelvic examination showed a small amount of vaginal bleeding with an
      evisceration of the small intestine through the vagina that exhibited healthy
      peristalsis. The eviscerated bowel, which seemed to be a part of the ileum, was
      carefully manually reduced transvaginally into the abdominal cavity. Laparoscopic
      observation revealed adhesions between the omentum, small intestine, and the
      peritoneum. Specifically, the small intestine was adhered around the vaginal
      cuff. An abdominal abscess was found in the left lower abdominal cavity. An
      adhesiotomy was performed and the abdominal abscess was removed and irrigated.
      Complete separation of the anterior and posterior vaginal cuff edges was
      obtained. The vaginal cuff was closed with interrupted 0-polydioxanone absorbable
      sutures without bowel injury. A 6-month follow-up examination revealed complete
      healing of the vaginal cuff. DISCUSSION: In this case, we were able to make use
      of both laparoscopic and transvaginal methods to perform a successful repair with
      a minimally invasive and safe technique. CONCLUSION: Laparoscopically assisted
      vaginal cuff suturing for vaginal cuff dehiscence after total laparoscopic
      hysterectomy was found to be effective, safe, and minimally invasive.

PMID- 29059610
TI  - Diagnosis and operative management of a perforated de Garengeot hernia.
AB  - INTRODUCTION: A de Garengeot hernia, a femoral hernia containing the appendix, is
      a difficult diagnosis often made intra-operatively when the hernia sac is opened.
      It is a rare finding, and complications are more frequent with a de Garengeot
      hernia. PRESENTATION OF CASE: A 92 year-old female presented to the emergency
      department (ED) complaining of abdominal pain. A computed tomographic (CT) scan
      of the abdomen and pelvis demonstrated a hernia anterior to the inguinal ligament
      without strangulation. Two weeks later the patient returned to the ED with
      worsening abdominal pain in the right lower quadrant. Repeat CT scan demonstrated
      a 7*4cm complex fluid collection in the right inguinal region, and the patient
      was taken to the operating room for exploration. The hernia sac was entered and
      found to contain the appendix with evidence of distal perforation. The appendix
      was taken out, and the hernia defect was repaired. The patient tolerated the
      procedure well. DISCUSSION: Femoral hernias have a high risk of incarceration due
      to the tightness of the femoral canal (Talini et al. 2015 [4]). Due to anatomic
      location of the appendix, de Garengeot hernias are most often seen on the right.
      Incarceration of the appendix is a clear etiology for appendicitis secondary to
      ischemia. CONCLUSION: Full preoperative workup for a femoral hernia often fails
      to diagnose the presence of the appendix within the hernia. It is important to
      have a high clinical suspicion for a de Garengeot's hernia in patients with
      incarcerated or strangulated right femoral hernias.

PMID- 29059612
TI  - Export of microplastics from land to sea. A modelling approach.
AB  - Quantifying the transport of plastic debris from river to sea is crucial for
      assessing the risks of plastic debris to human health and the environment. We
      present a global modelling approach to analyse the composition and quantity of
      point-source microplastic fluxes from European rivers to the sea. The model
      accounts for different types and sources of microplastics entering river systems
      via point sources. We combine information on these sources with information on
      sewage management and plastic retention during river transport for the largest
      European rivers. Sources of microplastics include personal care products,
      laundry, household dust and tyre and road wear particles (TRWP). Most of the
      modelled microplastics exported by rivers to seas are synthetic polymers from
      TRWP (42%) and plastic-based textiles abraded during laundry (29%). Smaller
      sources are synthetic polymers and plastic fibres in household dust (19%) and
      microbeads in personal care products (10%). Microplastic export differs largely
      among European rivers, as a result of differences in socio-economic development
      and technological status of sewage treatment facilities. About two-thirds of the
      microplastics modelled in this study flow into the Mediterranean and Black Sea.
      This can be explained by the relatively low microplastic removal efficiency of
      sewage treatment plants in the river basins draining into these two seas. Sewage
      treatment is generally more efficient in river basins draining into the North
      Sea, the Baltic Sea and the Atlantic Ocean. We use our model to explore future
      trends up to the year 2050. Our scenarios indicate that in the future river
      export of microplastics may increase in some river basins, but decrease in
      others. Remarkably, for many basins we calculate a reduction in river export of
      microplastics from point-sources, mainly due to an anticipated improvement in
      sewage treatment.

PMID- 29059611
TI  - Validating epilepsy diagnoses in routinely collected data.
AB  - PURPOSE: Anonymised, routinely-collected healthcare data is increasingly being
      used for epilepsy research. We validated algorithms using general practitioner
      (GP) primary healthcare records to identify people with epilepsy from anonymised
      healthcare data within the Secure Anonymised Information Linkage (SAIL) databank
      in Wales, UK. METHOD: A reference population of 150 people with definite epilepsy
      and 150 people without epilepsy was ascertained from hospital records and linked
      to records contained within SAIL (containing GP records for 2.4 million people).
      We used three different algorithms, using combinations of GP epilepsy diagnosis
      and anti-epileptic drug (AED) prescription codes, to identify the reference
      population. RESULTS: Combining diagnosis and AED prescription codes had a
      sensitivity of 84% (95% ci 77-90) and specificity of 98% (95-100) in identifying
      people with epilepsy; diagnosis codes alone had a sensitivity of 86% (80-91) and
      a specificity of 97% (92-99); and AED prescription codes alone achieved a
      sensitivity of 92% (70-83) and a specificity of 73% (65-80). Using AED codes only
      was more accurate in children achieving a sensitivity of 88% (75-95) and
      specificity of 98% (88-100). CONCLUSION: GP epilepsy diagnosis and AED
      prescription codes can be confidently used to identify people with epilepsy using
      anonymised healthcare records in Wales, UK.

PMID- 29059613
TI  - Capillary electrophoresis separation of phenethylamine enantiomers using amino
      acid based ionic liquids.
AB  - In recent years increasing interest was drawn towards ionic liquids in analytical
      separation science, such as capillary electrophoresis. Ionic liquids combining
      tetrabutylammonium cations with chiral amino acid based anions were prepared and
      investigated as capillary electrophoresis background electrolyte additives for
      the enantioseparation of ephedrine, pseudoephedrine, and methylephedrine isomers.
      For the optimization of buffer pH and ionic liquid concentration a design of
      experiments approach was performed. The best results for the separation of all
      enantiomers were achieved using 125mmol/L tetrabutylammonium l-argininate in a
      75mmol/L phosphate buffer pH 1.5 containing 30mmol/L beta-cyclodextrin.

PMID- 29059614
TI  - A liquid chromatography and tandem mass spectrometry method to determine 28 non
      volatile drugs of abuse in exhaled breath.
AB  - Exhaled breath carries aerosol micro-particles containing nonvolatile organic
      substances. Recently, the analysis of drugs of abuse (DOA) have become of
      interest in exhaled breath particles (EBP). In this study, a liquid
      chromatography - tandem mass spectrometry (LC-MS/MS) method was developed and
      validated to analyze 28 DOA in 30L of EBP collected on a permeable polymer
      filter. After extraction, the chromatographic separation was achieved on a UPLC
      BEH phenyl column using a mobile phase consisting of methanol and water both
      containing 4mmol/L ammonium formate and 0.05% ammonia. The column temperature was
      set at 50 degrees C and mobile phase flow rate 0.5mL/min in gradient mode with a
      total run time of 5min. The mass spectrometer was operated in positive
      electrospray ionization and selected reaction monitoring mode. Acquired limits of
      quantification were in the range of 1-66pg/filter for all substances except DM
      tramadol. Excellent linearity over the concentration range from LLOQs -
      15ng/filter with r2 values >0.99 and satisfactory recoveries (70-116% at
      100pg/filter) were achieved. During method application a total 26 samples were
      analyzed of which 24 were found to be positive for 13 analytes. The highest
      amount was found for methadone (56ng/filter) and the lowest amount was found for
      the methadone metabolite EDDP (2pg/filter) in two different samples.

PMID- 29059615
TI  - Development and validation of a high-performance liquid chromatography-tandem
      mass spectrometry assay for the quantification of Dexamphetamine in human plasma.
AB  - Dexamphetamine is registered for the treatment of attention deficit hyperactivity
      disorder and narcolepsy. Current research has highlighted the possible
      application of dexamphetamine in the treatment of cocaine addiction. To support
      clinical pharmacologic trials a new simple, fast, and sensitive assay for the
      quantification of dexamphetamine in human plasma using liquid chromatography
      tandem mass spectrometry (LC-MS/MS) was developed. Additionally, it is the first
      reported LC-MS assay with these advantages to be fully validated according to
      current US FDA and EMA guidelines. Human plasma samples were collected on an
      outpatient basis and stored at nominally -20 degrees C. The analyte and the
      internal standard (stable isotopically labeled dexamphetamine) were extracted
      using double liquid-liquid extraction (plasma-organic and organic-water) combined
      with snap-freezing. The aqueous extract was filtered and 2MUL was injected on a
      C18-column with isocratic elution and analyzed with triple quadrupole mass
      spectrometry in positive ion mode. The validated concentration range was from 2.5
      250ng/mL and the calibration model was linear. A weighting factor of 1 over the
      squared concentration was applied and correlation coefficients of 0.997 or better
      were obtained. At all concentrations the bias was within +/-15% of the nominal
      concentrations and imprecision was <=15%. All results were within the acceptance
      criteria of the latest US FDA guidance and EMA guidelines on method validation.
      In conclusion, the developed method to quantify dexamphetamine in human plasma
      was fit to support a clinical study with slow-release dexamphetamine.

PMID- 29059616
TI  - DRIFTS-based multivariate calibration and prediction of low-concentration
      polymorphic impurities in multiple lots of an active pharmaceutical ingredient,
      and outlier criteria.
AB  - Mixtures of two polymorphic impurities with one lot of the desired form of an
      Active Pharmaceutical Ingredient (API), mostly binary mixtures, with up to 2%
      wt/wt of an impurity, were used for multivariate modeling via Diffuse Reflectance
      Infrared Fourier Transform (DRIFT) spectra. The two obtained cross-validated
      models, significantly differing in accuracy, were used to predict the
      concentrations of these impurities in independent API lots. The predictions were
      found to be biased and with outliers, as revealed by the Q residuals criterion
      but not the other two outlier criteria. Updating the models with the spectra from
      the mixtures using multiple API lots produced very different calibration results:
      the model of the impurity with the strong IR response became noticeably worse,
      while the model of the impurity with less responsive IR signal changed only
      marginally. The updated models performed much better in the prediction as the
      bias for both polymorphs was reduced and the outlier-related issues mostly
      disappeared.

PMID- 29059617
TI  - The combination of four analytical methods to explore skeletal muscle
      metabolomics: Better coverage of metabolic pathways or a marketing argument?
AB  - OBJECTIVES: Metabolomics is an emerging science based on diverse high throughput
      methods that are rapidly evolving to improve metabolic coverage of biological
      fluids and tissues. Technical progress has led researchers to combine several
      analytical methods without reporting the impact on metabolic coverage of such a
      strategy. The objective of our study was to develop and validate several
      analytical techniques (mass spectrometry coupled to gas or liquid chromatography
      and nuclear magnetic resonance) for the metabolomic analysis of small muscle
      samples and evaluate the impact of combining methods for more exhaustive
      metabolite covering. DESIGN AND METHODS: We evaluated the muscle metabolome from
      the same pool of mouse muscle samples after 2 metabolite extraction protocols.
      Four analytical methods were used: targeted flow injection analysis coupled with
      mass spectrometry (FIA-MS/MS), gas chromatography coupled with mass spectrometry
      (GC-MS), liquid chromatography coupled with high-resolution mass spectrometry (LC
      HRMS), and nuclear magnetic resonance (NMR) analysis. We evaluated the global
      variability of each compound i.e., analytical (from quality controls) and
      extraction variability (from muscle extracts). We determined the best extraction
      method and we reported the common and distinct metabolites identified based on
      the number and identity of the compounds detected with low analytical variability
      (variation coefficient<30%) for each method. Finally, we assessed the coverage of
      muscle metabolic pathways obtained. RESULTS: Methanol/chloroform/water and
      water/methanol were the best extraction solvent for muscle metabolome analysis by
      NMR and MS, respectively. We identified 38 metabolites by nuclear magnetic
      resonance, 37 by FIA-MS/MS, 18 by GC-MS, and 80 by LC-HRMS. The combination led
      us to identify a total of 132 metabolites with low variability partitioned into
      58 metabolic pathways, such as amino acid, nitrogen, purine, and pyrimidine
      metabolism, and the citric acid cycle. This combination also showed that the
      contribution of GC-MS was low when used in combination with other mass
      spectrometry methods and nuclear magnetic resonance to explore muscle samples.
      CONCLUSION: This study reports the validation of several analytical methods,
      based on nuclear magnetic resonance and several mass spectrometry methods, to
      explore the muscle metabolome from a small amount of tissue, comparable to that
      obtained during a clinical trial. The combination of several techniques may be
      relevant for the exploration of muscle metabolism, with acceptable analytical
      variability and overlap between methods However, the difficult and time-consuming
      data pre-processing, processing, and statistical analysis steps do not justify
      systematically combining analytical methods.

PMID- 29059618
TI  - Development of a robust reporter gene based assay for the bioactivity
      determination of IL-5-targeted therapeutic antibodies.
AB  - Eosinophilic asthma is characterized by the eosinophilic inflammation with the
      allergen independent activation of Th2 lymphocytes. Since IL-5 plays an important
      role in the maturation, survival and migration of eosinophils, hence the
      pathogenesis of eosinophilic asthma, biotherapeutics targeting IL-5/IL-5Ralpha
      have been developed and/or marketed, including Mepolizumab, Reslizumab, and
      Benralizumab. Accurate determination of bioactivity is crucial for the safety and
      efficacy of therapeutic antibodies. The current mode of action (MOA) based method
      used in the quality control and stability tests for anti-IL-5 mAbs is anti
      proliferation assay, which is tedious with long duration and high variation. We
      describe here the development and validation of a reporter gene assay (RGA),
      based on an IL-5-dependent TF-1 cell line variant we established that stably
      expresses the luciferase reporter under the control of STAT5 response elements.
      After careful optimization, we demonstrate the excellent specificity, precision,
      accuracy and linearity of the established RGA. Our study also proves that the
      assay is superior on precision, sensitivity and assay simplicity to the anti
      proliferation assay. The established RGA is also applicable to another anti-IL
      5Ralpha mAb. These results show for the first time that this novel RGA, based on
      the IL-5-IL-5R-STAT5 pathway, can be a valuable supplement to the anti
      proliferation assay and employed in the bioactivity determination of anti-IL
      5/anti-IL-5Ralpha biotherapeutics.

PMID- 29059620
TI  - Analysis of potential risks from the bacterial communities associated with air
      contact surfaces from tilapia (Oreochromis niloticus) fish farming.
AB  - Tilapia farming is a promising growing sector in aquaculture. Yet, there are
      limited studies on microbiological risks associated to tilapia farms. The aim of
      the present study was to analyse the bacterial communities from solid surfaces in
      contact with air in a tilapia farm in order to evaluate the presence of bacteria
      potentially toxinogenic or pathogenic to humans or animals. Samples from a local
      tilapia farm (tank wall, aerator, water outlets, sink and floor) were analyzed by
      high throughput sequencing technology. Sequences were assigned to operational
      taxonomic units (OTUs). Proteobacteria was the main phylum represented in most
      samples (except for one). Cyanobacteria were a relevant phylum in the inner wall
      from the fattening tank and the wet floor by the pre-fattening tank.
      Bacteroidetes were the second phylum in relative abundance for samples from the
      larval rearing tank and the pre-fattening tank and one sample from the fattening
      tank. Fusobacteria showed highest relative abundances in samples from the larval
      rearing tank and pre-fattening tank. Other phyla (Verrucomicrobia,
      Actinobacteria, Firmicutes, Planktomycetes, Acidobacteria, Chloroflexi, Chlorobi,
      Gemmatiomonadetes or Fibrobacters) had lower relative abundances. A large
      fraction of the reads (ranging from 43.67% to 72.25%) were assigned to uncultured
      bacteria. Genus Acinetobacter (mainly A. calcoaceticus/baumanni) was the
      predominant OTU in the aerator of the fattening tank and also in the nearby sink
      on the floor. The genera Cetobacterium and Bacteroides showed highest relative
      abundances in the samples from the larval rearing tank and the pre-fattening
      tank. Genera including fish pathogens (Fusobacterium, Aeromonas) were only
      detected at low relative abundances. Potential human pathogens other than
      Acinetobacter were either not detected or had very low relative abundances (<
      0.01%). The results of the study suggest that the main risk factors to be
      monitored in tilapia farm are putative human pathogenic Acinetobacter and
      potential cyanotoxin-producing cyanobacteria.

PMID- 29059619
TI  - Association of residential greenness with obesity and physical activity in a US
      cohort of women.
AB  - There is evidence of several health benefits associated with neighborhood
      greenness, but reasons for this are unclear. Studies have found that those who
      live in greener neighborhoods are more physically active, and have lower rates of
      obesity. Relatively few studies have attempted to characterize associations
      between greenness and both obesity and physical activity concurrently, or among
      women who are at higher risk of developing cancer and for whom physical activity
      may be important for primary prevention. To address these gaps, we undertook a
      cross-sectional analysis of data from 50,884 women who enrolled in the Sister
      Study between 2003 and 2009. This cohort includes women aged 35-74 whose sister
      had been diagnosed with breast cancer. Residential measures of greenness were
      determined using the US National Land Cover database. Logistic regression was
      used to characterize associations between greenness, obesity, and physical
      activity. Adjustments were made for other possible confounders. Women who lived
      in areas with the highest tertile of greenness (based on a 500m buffer) had a
      reduced risk of obesity (body mass index (BMI) >= 30) relative to those in the
      lowest tertile (odds ratio (OR) = 0.83, 95% CI = 0.79-0.87). We also found that
      those the upper tertile of greenness were 17% more likely to expend more than
      67.1 metabolic equivalent (MET) hours per week when compared to those in the
      lowest tertile (OR = 1.17, 95% CI = 1.10-1.23). Beneficial associations between
      greenness and both obesity and physical activity were observed in urban and rural
      areas, and regionally, stronger associations were observed in the western census
      region in the US. Mediation analyses indicated that physical activity attenuated
      the association between greenness and obesity by 32%. Our findings indicate that,
      amongst US adult women at higher risks of breast cancer, residential proximity to
      greenness may help mitigate against sedentary behaviors that increase the risk of
      chronic disease.

PMID- 29059621
TI  - Short-term ozone exposure and asthma severity: Weight-of-evidence analysis.
AB  - To determine whether evidence indicates that short-term exposure to ambient
      concentrations of ozone in the United States can affect asthma severity, we
      systematically reviewed published controlled human exposure, epidemiology, and
      animal toxicity studies. The strongest evidence for a potential causal
      relationship came from epidemiology studies reporting increased emergency
      department visits and hospital admissions for asthma following elevated ambient
      ozone concentrations. However, while controlled exposure studies reported lung
      function decrements and increased asthma symptoms following high ozone exposures
      160-400 parts per billion [ppb]), epidemiology studies evaluating similar
      outcomes reported less consistent results. Animal studies showed changes in
      pulmonary function at high ozone concentrations (> 500ppb), although there is
      substantial uncertainty regarding the relevance of these animal models to human
      asthma. Taken together, the weight of evidence indicates that there is at least
      an equal likelihood that either explanation is true, i.e., the strength of the
      evidence for a causal relationship between short-term exposure to ambient ozone
      concentrations and asthma severity is "equipoise and above."

PMID- 29059622
TI  - FeCl3-catalyzed ethanol pretreatment of sugarcane bagasse boosts sugar yields
      with low enzyme loadings and short hydrolysis time.
AB  - An organosolv pretreatment system consisting of 60% ethanol and 0.025 mol.L-1
      FeCl3 under various temperatures was developed in this study. During the
      pretreatment, the highest xylose yield was 11.4 g/100 g raw material,
      representing 49.8% of xylose in sugarcane bagasse. Structural features of raw
      material and pretreated substrates were characterized to better understand how
      hemicellulose removal and delignification affected subsequent enzymatic
      hydrolysis. The 160  degrees C pretreated solid presented a remarkable glucose
      yield of 93.8% for 72 h. Furthermore, the influence of different additives on the
      enzymatic hydrolysis of pretreated solid was investigated. The results indicated
      that the addition of Tween 80 shortened hydrolysis time to 6 h and allowed a 50%
      reduction of enzyme loading to achieve the same level of glucose yield. This work
      suggested that FeCl3-catalyzed organosolv pretreatment could improve the
      enzymatic hydrolysis significantly and reduce the hydrolysis time and enzyme
      dosage with the addition of Tween 80.

PMID- 29059624
TI  - Biosorption performance evaluation of heavy metal onto aerobic granular sludge
      derived biochar in the presence of effluent organic matter via batch and
      fluorescence approaches.
AB  - In present study, the biosorption process of Cu(II) onto aerobic granular sludge
      derived biochar was evaluated in the absence and presence of effluent organic
      matter (EfOM) by using batch and fluorescence approaches. It was found that EfOM
      gave rise to enhancement of Cu(II) removal efficiency onto biochar, and the
      sorption data were better fitted with pseudo-second order model and Freundlich
      equation, in despite of the absence and presence of EfOM. According to excitation
      emission matrix (EEM), EfOM was mainly comprised by humic-like substances and
      fulvic-like substances and their intensities were reduced in the addition of
      biochar and Cu(II) from batch biosorption process. Synchronous fluorescence
      spectra coupled to two-dimensional correlation spectroscopy (2D-COS) further
      implied that a successive fluorescence quenching was observed in various EfOM
      fractions with the increasing Cu(II) concentration. Moreover, fulvic-like
      fraction was more susceptibility than other fractions for fluorescence quenching
      of EfOM.

PMID- 29059623
TI  - Optimization of membrane unit location in a full-scale membrane bioreactor using
      computational fluid dynamics.
AB  - The location of membrane units in the membrane tank is a key factor in the
      construction of a full-scale membrane bioreactor (MBR), as it would greatly
      affect the hydrodynamics in the tank, which could in turn affect the membrane
      fouling rate while running. Yet, in most cases, these units were empirically
      installed in tanks, no theory guides were currently available for the design of a
      proper location. In this study, the hydrodynamics in the membrane tank of a full
      scale MBR was simulated using computational fluid dynamics (CFD). Five indexes
      (iLu, iLa, iLb, iLint, iLw) were used to indicate the unit location, and each of
      them was discussed for their individual impact on the risk water velocity (v0.05)
      in the membrane unit region. An optimal design with all the indexes equaling 0.6
      was proposed, and was found to have a promotion of 146.9% for v0.05.

PMID- 29059625
TI  - Association of PM2.5 with sleep-disordered breathing from a population-based
      study in Northern Taiwan urban areas.
AB  - Recent studies suggest that exposure to air pollution might be associated with
      severity of sleep-disordered breathing (SDB). However, the association between
      air pollution exposure, especially particulate matter with aerodynamic diameters
      <= 2.5 MUm (PM2.5), and SDB is still unclear. We collected 4312 participants'
      data from the Taipei Medical University Hospital's Sleep Center and air pollution
      data from the Taiwan Environmental Protection Administration. Associations of
      particulate matter with aerodynamic diameters <=10 MUm (PM10), PM2.5, nitrogen
      dioxide (NO2), ozone (O3) and sulfur dioxide (SO2) with apnea-hypopnea index
      (AHI) and oxygen desaturation index (ODI) were investigated by generalized
      additive models. We found that an interquartile range (IQR) increase in 1-year
      mean PM2.5 (3.4 MUg/m3) and NO2 (2.7 ppb) was associated with a 4.7% and 3.6%
      increase in AHI, respectively. We also observed the association of an IQR
      increase in 1-year mean PM2.5 with a 2.5% increase in ODI. The similar pattern
      was found in the association of daily mean PM2.5 exposure with increased AHI.
      Moreover, participants showed significant AHI and ODI responses to air pollution
      levels in spring and winter. We concluded that exposure to PM2.5 was associated
      with SDB. Effects of air pollution on AHI and ODI were significant in spring and
      winter.

PMID- 29059626
TI  - Contamination of short-chain chlorinated paraffins to the biotic and abiotic
      environments in the Bohai Sea.
AB  - Short-chain chlorinated paraffins (SCCPs) have been produced and emitted
      intensively around the Bohai Sea, potentially causing risks to this unique
      ecosystem and one of primary fishery resources in China and busiest seaways in
      the world. Little is known about fate, cycling, and sources of SCCPs in the Bohai
      Sea biotic and abiotic environment. In this study, we combined a marine food web
      model with a comprehensive atmospheric transport-multiple phase exchange model to
      quantify SCCPs in the biotic and abiotic environment in the Bohai Sea. We
      performed multiple modeling scenario investigations to examine SCCP levels in
      water, sediment, and phytoplankton. We assessed numerically dry and wet
      depositions, biomagnification and bioaccumulation of SCCPs in the Bohai Sea
      marine food web. Results showed declining SCCP levels in water and sediment with
      increasing distance from the coastline, and so do dry and wet depositions. The
      net deposition overwhelmed the water-air exchange of SCCPs due to their current
      use in China, though the diffusive gas deposition fluctuated monthly subject to
      mean wind speed and temperature. A risk assessment manifests that SCCPs levels in
      the Bohai Sea fish species are at present not posing risks to the residents in
      the Bohai Sea Rim region. We identified that the SCCP emission sources in the
      south of the Bohai Sea made a primary contribution to its loadings to the
      seawater and fish contamination associated with the East Asian summer monsoon. In
      contrast, the SCCP emissions from the north and northwest regions of the Bohai
      Sea were major sources contributing to their loading and contamination to Bohai
      Sea food web during the wintertime, potentially driven by the East Asian winter
      monsoon.

PMID- 29059627
TI  - Adsorption and co-adsorption of graphene oxide and Ni(II) on iron oxides: A
      spectroscopic and microscopic investigation.
AB  - Graphene oxide (GO) may strongly interact with toxic metal ions and mineral
      particles upon release into the soil environment. We evaluated the mutual effects
      between GO and Ni (Ni(II)) with regard to their adsorption and co-adsorption on
      two minerals (goethite and hematite) in aqueous phase. Results indicated that GO
      and Ni could mutually facilitate the adsorption of each other on both goethite
      and hematite over a wide pH range. Addition of Ni promoted GO co-adsorption
      mainly due to the increased positive charge of minerals and cation-pi
      interactions, while the presence of GO enhanced Ni co-adsorption predominantly
      due to neutralization of positive charge and strong interaction with oxygen
      containing functional groups on adsorbed GO. Increasing adsorption of GO and Ni
      on minerals as they coexist may thus reduce their mobility in soil. Extended X
      ray absorption fine structure (EXAFS) spectroscopy data revealed that GO altered
      the microstructure of Ni on minerals, i.e., Ni formed edge-sharing surface
      species (at RNi-Fe~3.2 A) without GO, while a GO-bridging ternary surface
      complexes (at RNi-C~2.49 A and RNi-Fe~4.23 A) was formed with GO. These findings
      improved the understanding of potential fate and toxicity of GO as well as the
      partitioning processes of Ni ions in aquatic and soil environments.

PMID- 29059628
TI  - Co-selection of antibiotic resistance via copper shock loading on bacteria from a
      drinking water bio-filter.
AB  - Heavy metal contamination of source water frequently occurred in developing
      countries as a result of accidents. To address the problems, most of the previous
      studies have focused on engineering countermeasures. In this study, we
      investigated the effects of heavy metals, particularly copper, on the development
      of antibiotic resistance by establishing a copper shock loading test. Results
      revealed that co-selection occurred rapidly within 6 h. Copper, at the levels of
      10 and 100 mg/L, significantly increased bacterial resistance to the antibiotics
      tested, including rifampin, erythromycin, kanamycin, and a few others. A total of
      117 antimicrobial-resistance genes were detected from 12 types of genes, and the
      relative abundance of most genes (particularly mobile genetic elements intIand
      transposons) was markedly enriched by at least one fold. Furthermore, the copper
      shock loading altered the bacterial community. Numerous heavy metal and
      antibiotic resistant strains were screened out and enriched. These strains are
      expected to enhance the overall level of resistance. More noticeably, the
      majority of the co-selected antibiotic resistance could sustain for at least 20 h
      in the absence of copper and antimicrobial drugs. Resistance to vancomycin,
      erythromycin and lincomycin even could remain for 7 days. The prominent selection
      pressure by the copper shock loading implies that a real accident most likely
      poses similar impacts on the water environment. An accidental release of heavy
      metals would not only cause harm to the ecological environment, but also
      contribute to the development of bacterial antibiotic resistance. Broader
      concerns should be raised about the biological risks caused by sudden releases of
      pollutants by accidents.

PMID- 29059629
TI  - Chemical composition and source apportionment of PM10 at an urban background site
      in a high-altitude Latin American megacity (Bogota, Colombia).
AB  - Bogota registers frequent episodes of poor air quality from high PM10
      concentrations. It is one of the main Latin American megacities, located at 2600
      m in the tropical Andes, but there is insufficient data on PM10 source
      contribution. A characterization of the chemical composition and the source
      apportionment of PM10 at an urban background site in Bogota was carried out in
      this study. Daily samples were collected from June 2015 to May 2016 (a total of
      311 samples). Organic carbon (OC), elemental carbon (EC), water soluble compounds
      (SO42-, Cl-, NO3-, NH4+), major elements (Al, Fe, Mg, Ca, Na, K, P) and trace
      metals (V, Cd, Pb, Sr, Ba, among others) were analyzed. The results were
      interpreted in terms of their variability during the rainy season (RS) and the
      dry season (DS). The data obtained revealed that the carbonaceous fraction (~51%)
      and mineral dust (23%) were the main PM10 components, followed by others (15%),
      Secondary Inorganic Compounds (SIC) (11%) and sea salt (0.4%). The average
      concentrations of soil, SIC and OC were higher during RS than DS. However, peak
      values were observed during the DS due to photochemical activity and forest
      fires. Although trace metals represented <1% of PM10, high concentrations of
      toxic elements such as Pb and Sb on RS, and Cu on DS, were obtained. By using a
      PMF model, six factors were identified (~96% PM10) including fugitive dust, road
      dust, metal processing, secondary PM, vehicles exhaust and industrial emissions.
      Traffic (exhaust emissions + road dust) was the major PM10 source, accounting for
      ~50% of the PM10. The results provided novel data about PM10 chemical
      composition, its sources and its seasonal variability during the year, which can
      help the local government to define control strategies for the main emission
      sources during the most critical periods.

PMID- 29059630
TI  - Anthropogenic nitrogen deposition alters growth responses of European beech
      (Fagus sylvativa L.) to climate change.
AB  - Global change affects the functioning of forest ecosystems and the services they
      provide, but little is known about the interactive effects of co-occurring global
      change drivers on important functions such as tree growth and vitality. In the
      present study we quantified the interactive (i.e. synergistic or antagonistic)
      effects of atmospheric nitrogen (N) deposition and climatic variables
      (temperature, precipitation) on tree growth (in terms of tree-ring width, TRW),
      taking forest ecosystems with European beech (Fagus sylvatica L.) as an example.
      We hypothesised that (i) N deposition and climatic variables can evoke non
      additive responses of the radial increment of beech trees, and (ii) N loads have
      the potential to strengthen the trees' sensitivity to climate change. In young
      stands, we found a synergistic positive effect of N deposition and annual mean
      temperature on TRW, possibly linked to the alleviation of an N shortage in young
      stands. In mature stands, however, high N deposition significantly increased the
      trees' sensitivity to increasing annual mean temperatures (antagonistic effect on
      TRW), possibly due to increased fine root dieback, decreasing mycorrhizal
      colonization or shifts in biomass allocation patterns (aboveground vs.
      belowground). Accordingly, N deposition and climatic variables caused both
      synergistic and antagonistic effects on the radial increment of beech trees,
      depending on tree age and stand characteristics. Hence, the nature of
      interactions could mediate the long-term effects of global change drivers
      (including N deposition) on forest carbon sequestration. In conclusion, our
      findings illustrate that interaction processes between climatic variables and N
      deposition are complex and have the potential to impair growth and performance of
      European beech. This in turn emphasises the importance of multiple-factor studies
      to foster an integrated understanding and models aiming at improved projections
      of tree growth responses to co-occurring drivers of global change.

PMID- 29059631
TI  - Mode of action characterization for adverse effect of propranolol in Daphnia
      magna based on behavior and physiology monitoring and metabolite profiling.
AB  - Studies are underway to gather information about the mode of action (MOA) of
      emerging pollutants that could guide practical environmental decision making.
      Previously, we showed that propranolol, an active pharmaceutical ingredient, had
      adverse effects on Daphnia magna that were similar to its pharmaceutical action.
      In order to characterize the mode of action of propranolol in D. magna, which is
      suspected to be organ-specific pharmaceutical action or baseline toxicity, we
      performed time-series monitoring of behavior along with heart rate measurements
      and nuclear magnetic resonance (NMR) based metabolite profiling. Principle
      component analysis (PCA) and hierarchical clustering were used to categorize the
      mode of action of propranolol among 5 chemicals with different modes of action.
      The findings showed that the mode of action of propranolol in D. magna is organ
      specific and vastly different from those of narcotics, even though metabolite
      regulation is similar between narcotic and non-narcotic candidates. The method
      applied in this study seems applicable to rapid characterization of the MOA of
      other cardiovascular pharmaceutical ingredients.

PMID- 29059632
TI  - Consistency of commonly used orthopedic special tests of the shoulder when used
      with the McKenzie system of mechanical diagnosis and therapy.
AB  - BACKGROUND: Shoulder Orthopedic Special Tests (OSTs) are used to assist with
      diagnosis in shoulder disorders. Issues with reliability and validity exist,
      making their interpretation challenging. Exploring OST results on repeated
      testing within Mechanical Diagnosis and Therapy (MDT) shoulder classifications
      may offer insight into the poor performance of these tests. OBJECTIVES: To
      investigate in patients with shoulder complaints, whether MDT classifications
      affect the agreement of OST results over the course of treatment. METHODS: An
      international group of MDT clinicians recruited 105 patients with shoulder
      problems. Three commonly used OSTs (Empty Can, Hawkins-Kennedy, and Speed's
      tests) were utilized. Results of the OSTs were collected at sessions 1, 3, 5 and
      8, or at discharge from an MDT classification-based treatment. The Kappa
      statistic was utilized to determine the agreement of the OST results over time
      for each of the MDT classifications. RESULTS: The overall Kappa values for Empty
      Can, Hawkins-Kennedy and Speed's tests were 0.28 (SE = 0.07), 0.28 (SE = 0.07)
      and 0.29 (SE = 0.07), respectively. The highest level of agreement was for
      Articular Dysfunction for the Empty Can test (0.84, SE = 0.19). For shoulder
      Derangements, there was no agreement for any of the OSTs (P values > 0.05).
      CONCLUSION: The lack of agreement when the OSTs were consecutively tested in the
      presence of the MDT Derangement classification contrasted with the other MDT
      classifications. The presence of Derangement was responsible for reducing the
      overall agreement of commonly used OSTs and may explain the poor consistency for
      OSTs.

PMID- 29059633
TI  - Validity of clinical measures of smooth pursuit eye movement control in patients
      with idiopathic neck pain.
AB  - BACKGROUND: Electrooculography is useful in detecting smooth pursuit neck torsion
      (SPNT) abnormalities in patients with neck pain, however, a validated, clinically
      relevant measure is lacking. OBJECTIVES: To explore the validity of visual
      assessment of formal and clinical videotaped SPNT tests in comparison to
      electrooculography. DESIGN: Cross-sectional observational study. METHOD: Twenty
      patients with idiopathic neck pain (INP) and twenty healthy controls performed
      the electrooculography SPNT test: first in neutral, then 45 degrees  trunk-under
      head torsion to the left then right. The formal video test involved the
      participant following a horizontal laser stimulus simultaneous to
      electrooculography. The clinical video test was then performed where the
      participant followed the clinician's finger in the horizontal direction. One
      blinded investigator interpreted and analysed the electrooculography trace and
      two others interpreted the videos. RESULTS: Patients with INP had a significantly
      (p < 0.05) greater SPNT difference than healthy controls. Visual observation of
      the formal test had 82.5% agreement with electrooculography and showed fair
      sensitivity (63.5%) and good specificity (89.6) whilst the clinical test had 65%
      agreement with electrooculography and showed poor sensitivity (27.3%) and good
      specificity (79.3%). There was an 82.5% agreement between investigators for the
      formal video taped measure. CONCLUSIONS: Visual analysis of assessment of SPNT is
      sufficient for detecting SPNT abnormalities in patients with INP. Accuracy of the
      clinical method could be improved by, altering how the visual stimulus is
      presented and including subjective reporting of symptoms to aid diagnosis
      resulting in implications for future research.

PMID- 29059634
TI  - The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial
      cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in
      the tumour microenvironment.
AB  - BACKGROUND: Human Leucocyte Antigen- E (HLA-E) has been reported as both a
      positive and negative prognostic marker in cancer. This apparent discrepancy may
      be due to opposing actions of HLA-E on tumour-infiltrating immune cells.
      Therefore, we evaluated HLA-E expression and survival in relation to the presence
      of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). METHODS:
      Tissue microarrays (TMAs) of endometrial tumours were used for
      immunohistochemical staining of parameters of interest. The combined impact of
      clinical, pathological and immune parameters on survival was analysed using log
      rank testing and Cox regression analyses. RESULTS: Upregulation of HLA-E was
      associated with an improved disease-free and disease-specific survival in
      univariate analysis (HR 0.58 95% CI 0.37-0.89; HR 0.42 95% CI 0.25-0.73,
      respectively). In multivariate analysis, the presence of NK cells predicts
      survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09-0.91)
      when HLA-E expression is upregulated; but it is associated with a worse prognosis
      when HLA-E expression is normal (HR 13.43, 95% CI 1.70-106.14). By contrast, the
      prognostic benefit of T cells was not modulated by HLA-E expression. CONCLUSIONS:
      Taken together, we demonstrate that the prognostic benefit of NK cells, but not T
      cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a
      model to explain our observations.

PMID- 29059635
TI  - Phase II randomised discontinuation trial of cabozantinib in patients with
      advanced solid tumours.
AB  - BACKGROUND: Cabozantinib is an inhibitor of tyrosine kinases, including MET,
      vascular endothelial growth factor receptor, AXL and RET. This multi-cohort phase
      II randomised discontinuation trial explored anticancer activity of cabozantinib
      in nine tumour types. PATIENTS AND METHODS: Cabozantinib was administered (100
      mg, once daily) to patients with advanced, recurrent or metastatic cancers. Those
      with stable disease at week 12 were randomised 1:1 to cabozantinib or placebo.
      Primary end-points were objective response rate (ORR) at week 12 and progression
      free survival (PFS) in the randomised phase. RESULTS: A total of 526 patients
      were enrolled. The highest ORR was observed in ovarian cancer (OC) (21.7%); the
      largest PFS benefit was observed in castration-resistant prostate cancer (CRPC)
      (median 5.5 versus 1.4 months for placebo; hazard ratio 0.14, 95% confidence
      interval: 0.04, 0.52). Disease control rates were >40% for CRPC, OC, melanoma,
      metastatic breast cancer (MBC), hepatocellular carcinoma (HCC) and non-small cell
      lung cancer. Median duration of response ranged from 3.3 (MBC) to 11.2 months
      (OC). Encouraging efficacy results and symptomatic improvements prompted early
      suspension of the randomised stage and conversion to open-label non-randomised
      expansion cohorts. Dose reductions to manage adverse events (AEs) occurred in
      48.7% of patients. The most frequent grade III-IV AEs were fatigue (12.4%),
      diarrhoea (10.5%), hypertension (10.5%) and palmar-plantar erythrodysesthesia
      syndrome (8.7%). CONCLUSIONS: Clinical antitumour activity of cabozantinib was
      observed in a subset of tumour types: CRPC and OC were evaluated further in
      expansion cohorts. Phase III programs were initiated in CRPC and HCC.
      Interpretation of efficacy outcomes was limited by early termination of the
      randomised portion of the trial. TRIAL REGISTRATION NUMBER: NCT00940225.

PMID- 29059636
TI  - Knowledge, attitude, and practices regarding miscarriage: A cross-sectional study
      among Flemish midwives.
AB  - OBJECTIVE: to examine the knowledge, attitude and practices (KAP) of Flemish
      midwives regarding miscarriage. DESIGN AND SETTING: a cross-sectional KAP study
      was conducted in 28 hospitals in Flanders (Northern region of Belgium) from
      September 2015 to January 2016. PARTICIPANTS: a total of 647 out of 1200 midwives
      (53.9%) working on maternity, labour and gynaecological wards, maternal and
      neonatal (intensive) care units, antenatal consultations, and reproductive
      medicine were recruited. MEASUREMENTS: data were collected using a semi
      structured, self-administered questionnaire. FINDINGS: the mean knowledge score
      was 6.31 out of 10. Of all participants, 47% recently cared for couples with
      miscarriage, and the majority (97%) indicated a key role for midwives in the
      psychosocial support of those couples. Lack of time, incapability and fear of
      being overwhelmed by their own feelings were identified as main barriers for
      psychosocial support. Knowledge was more often evaluated as adequate when
      miscarriage was included in the midwifery education (31% vs. 17.3%, chi2 =
      12.965, df = 1, p<0.001). Midwives trained for the topic 'miscarriage' more often
      valued their role in miscarriage care (98.8% vs. 94.1%, chi2 = 11.002, df = 1, p
      = 0.001). They considered themselves being more capable to provide adequate
      psychosocial support when feeling sufficiently trained in communicative skills
      (77.7% vs. 33.8%, chi2 = 96.574, df = 1, p<0.001). The majority (72.4%) indicated
      a lack of knowledge regarding miscarriage. Almost 89% expressed a need for extra
      training. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: midwives in Flanders assist
      in the care for couples with miscarriage and consider themselves as a key
      healthcare provider in the psychosocial support. This study highlighted several
      barriers regarding miscarriage care, e.g. a lack of knowledge and incapability.
      Adequate training in knowledge and communication skills is important and
      necessary in order to promote appropriate care to couples experiencing pregnancy
      loss and increase awareness among all health professionals involved in obstetric
      care. Further research should investigate to what extent miscarriage is included
      in the educational midwifery programmes, and how the current healthcare practice
      regarding miscarriage care is organised.

PMID- 29059637
TI  - Visualizing spatially decomposed intermolecular correlations in the infrared
      spectra of aprotic liquids.
AB  - Infrared (IR) spectroscopy is commonly used to study intermolecular interactions
      in the liquid phase, including solvation phenomena. On the other hand, ab initio
      molecular dynamics (AIMD) simulations offer the possibility to obtain IR spectra
      from first principles. Surpassing the experiment, AIMD simulations can deliver
      additional information on the spatial intermolecular correlations underlying the
      IR spectrum of the liquid. Although such correlations contribute significantly to
      the IR spectra of associated liquids, such as water, they are equally important
      in the case of aprotic solvents, where dipole-dipole interactions are dominant.
      Here, the extent and non-trivial character of the spatial correlations in the IR
      spectra are demonstrated on the example of gamma-butyrolactone (GBL), an
      important solvent in the rechargeable cell industry.

PMID- 29059638
TI  - High quality rendering of protein dynamics in space filling mode.
AB  - Producing high quality depictions of molecular structures has been an area of
      academic interest for years, with visualisation tools such as UCSF Chimera,
      Yasara and PyMol providing a huge number of different rendering modes and
      lighting effects. However, no visualisation program supports per-pixel lighting
      effects with shadows whilst rendering a molecular trajectory in space filling
      mode. In this paper, a new approach to rendering high quality visualisations of
      molecular trajectories is presented. To enhance depth, ambient occlusion is
      included within the render. Shadows are also included to help the user perceive
      relative motions of parts of the protein as they move based on their
      trajectories. Our approach requires a regular grid to be constructed every time
      the molecular structure deforms allowing per-pixel lighting effects and ambient
      occlusion to be rendered every frame, at interactive refresh rates. Two different
      regular grids are investigated, a fixed grid and a memory efficient compact grid.
      The algorithms used allow trajectories of proteins comprising of up to 300,000
      atoms in size to be rendered at ninety frames per second on a desktop computer
      using the GPU for general purpose computations. Regular grid construction was
      found to only take up a small proportion of the total time to render a frame. It
      was found that despite being slower to construct, the memory efficient compact
      grid outperformed the theoretically faster fixed grid when the protein being
      rendered is large, owing to its more efficient memory access patterns. The
      techniques described could be implemented in other molecular rendering software.

PMID- 29059639
TI  - [Complexity of the phenomenon of life - the challenge for medicine].
AB  - The human organism presents a complex biological system that has hierarchical
      organization. The lowest, basal hierarchical level is composed of chemical
      molecules. The system's structure as "the whole" is maintained by complex
      interactions of its parts (molecules). New forms and functions, not present in
      molecules themselves emerge from their orchestrated and coordinated interaction,
      creating the novel "whole". The "whole" is not a simple summation of its parts.
      Therefore, on the basis of reductionist analysis and solely on the list of
      component elements of biological systems it is not possible to predict the future
      form and function of the "whole". The information included in genes is not
      directly or proportionally expressed as the phenotype. The phenotype is based on
      secondary information and arises from the complex interaction of component
      elements of the system. On a basal (molecular) level, biological systems function
      according to self-organization rules. No central regulatory device is providing
      instruction for molecular interaction. Regulatory centers that coordinate the
      system are dispersed all over the system from molecular level up, keeping it in
      order and preventing a system to enter the chaos space. Advances in biology and
      development of new research technologies, as well as bioinformatics, computer
      sciences and mathematical modeling have enabled research on interaction of
      cellular macromolecules (proteins, DNA, RNA, etc.) that in a living cell are
      organized into large dynamic network. Some rules of a structural and functional
      networks' properties, as well as their organization were discovered. The above
      research area is regarded as a new academic field termed systems biology. Based
      on systems biology, many new concepts in medicine, particularly the mechanisms of
      biogenesis and development of diseases have emerged have potential application
      for early diagnostics and therapy.

PMID- 29059640
TI  - Assessment of release factors of b-type natriuretic peptide during the exercise
      test in patients with diabetes and after myocardial infarction with preserved
      left ventricular systolic function.
AB  - INTRODUCTION: The increased concentration of B-type natriuretic peptide (BNP) is
      an expression of overload of the heart, regardless of the cause. Exercise test is
      a helpful method of assessing the exercise tolerance and myocardial ischemia. THE
      AIM: The aim of the study is to determine the factors that cause the release of
      BNP during the exercise test. MATERIAL AND METHODS: The study included 99
      patients with diabetes and after myocardial infarction with preserved left
      ventricular ejection fraction (EF>=40%). Before performing the exercise test
      (ExT) echocardiography was performed and blood sample was taken to determine BNP.
      Immediately after the exercise test another blood sample was taken to determine
      BNP. RESULTS: In 22 patients (22%) an increase in BNP >=35pg/ml after the
      exercise test was observed. In patients with EF.

PMID- 29059641
TI  - [Attitudes of polish physicians towards extending competencies of nurses and
      midwives with respect to prescribing medicines].
AB  - INTRODUCTION: Due to the amendment of the Nurse and Midwife professions Act,
      since 1st of January 2016 Polish nurses and midwives with certain qualifications
      are able to prescribe medicines and referral for diagnostic tests. THE AIM: To
      analyse attitudes of physicians on new professional competencies of nurses and
      midwives regarding: prescribing medicines and referring patients for certain
      diagnostic tests. MATERIAL AND METHODS: In the study took part 436 physicians
      (245 women, 193 man). The average age was 36,6 years old (min.: 21; max.: 76; SD:
      11,65; median: 31). 274 people lived in a city with over 500 thousand citizens,
      70 people - city below 100 thousand citizens, 54 people - city between 100-500
      thousands citizens and 14 people lived in a country. Most of people lived in
      masovian district. Authors prepared and validated own questionnaire, which
      contained statements assessed in Likert scale (1-strongly disagree, 5-stronlgy
      agree). It contained 22 questions about opinions of new abilities of nurses and
      midwives. The questionnaire was sent three times to Regional Medical Chamber in
      Warsaw via an online questionnaire:
      https://docs.google.com/forms/d/1cxiaJFPxDVphByhBTk4gDIBsm6bQsxGLVXDK-RtpGnk/ The
      reliability of the questionnaire used was tested in a pilot study by the
      coefficient alpha-Cronbach, which amounted to 0.937. Due to the fact that the
      study was performed in a group of doctors they did not require the consent of the
      Bioethics Committee, of Medical University of Warsaw to carry them out. The
      results are presented using descriptive statistics, which were obtained through
      statistical analysis using Microsoft Excel and StatSoft Statistica 12.0 (license
      Medical University of Warsaw). RESULTS: 53% of doctors claim that the new powers
      do not improve patient care. 35% of respondents disagreed with the opinion that
      the new powers will raise the prestige of professional nurses and midwives. At
      the same time 49% believe that prescriptions for nurses and midwives reduce the
      responsibilities of doctors. Only 9% agreed that the new abilities are needed in
      Poland. 65% of doctors have expressed the opinion that nurses and midwives should
      not have permission to prescriptions and 81% believe that they are not prepared
      for those abilities. CONCLUSION: Doctors have divided opinion about the benefits
      of the introduction of the nursing prescriptions for the patient. It is
      therefore, considered an information campaign through the mass media, or training
      in the workplace, where they will be presented in an objective manner the
      consequences of the introduction of new regulations.

PMID- 29059642
TI  - Diagnostic algorithm and peculiarities of monitoring for infants with disorders
      of the gastrointestinal tract.
AB  - INTRODUCTION: The most common medical conditions in infants, which belong to
      pediatric and gastroenterological disease areas, are functional gastrointestinal
      disorders, food hypersensitivity and food allergy. First of all, these symptoms
      can disguise lactase deficiency, cow's milk protein allergy, eosinophilic
      gastroenteritis, allergic proctocolitis, gastrointestinal manifestations of
      atopic dermatitis, functional disorders of gastrointestinal and biliary tract,
      etc. The aim of our study was to develop an algorithm of monitoring for infants
      with disorders of the gastrointestinal tract and to study the efficacy of
      probiotic and enzyme replacement therapy. Materials and metods: 47 children aged
      1 to 3 years with gastrointestinal and atopic dermatitis symptoms underwent
      clinical and laboratory examinations. RESULTS: Analysis of additional examination
      revealed the causes of gastrointestinal disorders, and the following diagnoses
      were made: 15 children (32 %) had secondary lactase deficiency, 9 children (19 %)
      had sensitization to cow's milk protein and caseins. Molecular-genetic analysis
      of S > T polymorphism at position 13910 of lactase gene (LST) demonstrated that
      C/C-13910 genotype was observed in 44.7 % of children, S/T-13910 heterozygous
      genotype was found in 36.2 %, and 19.1 % of children had T/T-13910 genotype;
      these were interpreted in conjunction with other clinical criteria for
      verification of secondary lactase deficiency diagnosis. CONCLUSIONS: Assessment
      of children over time during their treatment showed that combined therapy using
      lactase preparation and probiotics contributed to relief of clinical symptoms.
      All patients had their fecal pH increased (> 5.5), whereas the majority of
      children demonstrated improvement yet on days 2-3 (i.e., decrease in pain
      syndrome, flatulency, and stool frequency; restoration of normal stool
      consistency). Based on the obtained data, we proposed a practical algorithm for
      verification and monitoring of children with gastrointestinal disorders.

PMID- 29059643
TI  - Assessment of rehabilitation potential in patients with vascular dysfunction
      caused by undifferentiated connective tissue dysplasia.
AB  - INTRODUCTION: Degradation of collagen, inherent to undifferentiated connective
      tissue dysplasia (UCTD) syndrome, also influences the changes in the structure of
      vascular walls. This contributes to the development of configured vascular
      anomalies, which are an independent predictor of vascular accident risk. Such
      diversity of UCTD manifestations requires development of prognostic criteria for
      rehabilitation potential, correction of which may contribute to recovery process
      in case of development of vascular catastrophe. Study aim is to evaluate the
      rehabilitation potential in patients with vascular dysfunction and underlying
      UCTD. MATERIALS AND METHODS: The study involved 150 male patients with confirmed
      diagnosis of UCTD (average age - 26.4 +/- 0.6 years). All patients had a complex
      clinical and instrumental examination. Phenotypic and UCTD visceral stigmas, UCTD
      biochemical markers were analyzed, followed by statistical processing of the
      results by method of variotional statistics. RESULTS: We revealed the high degree
      of direct correlation between the presence of vascular dysfunction and myxomatous
      degeneration of the mitral valve (r = + 0.76, p.

PMID- 29059644
TI  - Resveratrol has a positive effect on parameters of central hemodynamics and
      myocardial ischemia in patients with stable coronary heart disease.
AB  - INTRODUCTION: Cardiovascular diseases, and primarily coronary heart disease
      (CHD), are the leading cause of mortality in the developing countries, including
      Ukraine. Prognosis for patients with CHD depends mainly on progression of
      coronary atherosclerosis (ASVD). Molecular mechanisms of atherogenesis are
      studied in detail in order to find new targets of pharmacological intervention.
      THE AIM: to study the effect of resveratrol on parameters of central hemodynamics
      and myocardial ischemia in patients with stable coronary heart disease (CHD).
      MATERIAL AND METHODS: The research involved 85 patients with CHD: stable angina
      pectoris, FC II, and 30 healthy individuals made up the control group. Patients
      with CHD were randomized into the research group (30 people) and the comparison
      group (55 people). Patients of the comparison group were prescribed the standard
      therapy (Beta-blockers, statins, aspirin). Resveratrol at a dose of 100 mg per os
      daily was added to standard treatment of the patients of the research group. The
      day before randomization and 2 months after the prescribing therapy to the
      patients, echocardiography (echo) and 24 hour Holter ECG monitoring were made.
      RESULTS: Diastolic dysfunction of the left ventricle (LV) in the form of
      violation of relaxation (type I) had been found in 100 % of patients with CHD.
      The 24 hour Holter ECG monitoring revealed episodes of myocardial ischemia
      (sigmat ST depr) (11.07+2.81 episodes a day), premature atrial contractions
      (PACs) and premature ventricular contractions (PVCs) in patients with stable CHD.
      After a two-month term of therapy in all patients with CHD, left ventricular
      systolic function in terms of ejection fraction (EF) of LV significantly improved
      (by 9.7 % in the research group and by 3.2 % in the comparison group). LV
      diastolic function improved in both groups in terms of the ratio of the phases of
      the transmitral flow E/A, dominating in the research group (r=0.004). DT value
      dropped significantly influenced by resveratrol (by 13 %), in the comparison
      group it didn't change. In both groups IVRT significance decreased (r < 0.05).
      According to the 24 hour Holter ECG monitoring, in patients, additionally taking
      resveratrol, sigmat ST depr decreased by 45.9 %, that prevailed the result of the
      comparison group by 25.2 %. Under the influence of resveratrol, unlike in the
      comparison group, the number of PACs and PVCs was significantly reduced.
      CONCLUSIONS: The data have shown cardioprotective properties of resveratrol and
      its applicability in the treatment of patients with CHD.

PMID- 29059645
TI  - [Prevention postpartum hemorrhage].
AB  - INTRODUCTION: Postpartum hemorrhage remains a leading cause of maternal morbidity
      and mortality. THE AIM: To evaluate the effectiveness of oxytocin into the
      umbilical vein for the prevention of postpartum hemorrhage. MATERIALS AND
      METHODS: A total of 105 women were included. Formed two groups. In group, I (n =
      51) - as prevention of bleeding was administered oxytocin in the umbilical cord
      vein. In group, II (n = 54) 10 IU oxytocin was carried out by intramuscular
      injection in the thigh during the first minute after birth. RESULTS: The duration
      of III stage of labor - 7,47 +/- 1,39 minutes in group, I, 9,5 +/- 1 minutes - in
      II (p>0,05). Pathology III stage of labor and the early postpartum period
      (placenta defect, tight attachment of the placenta, early hypo tonic bleeding)
      was observed in 9 (17,6%) in group, I and in 6 (11%) - II. Total blood loss
      during labor: in group, I - 57,19 +/- 189 ml in the II - 221,6 +/- 30,14 ml
      (p>0,05). In group, I, the mean hemoglobin content in peripheral blood before
      birth was 117 +/- 2,55 g / l, in II - 123 +/- 3,56 g / l (p>0,05). After birth,
      the average level of hemoglobin in the group, I was down to 112 +/- 3,93 g / l,
      in II - up to 116 +/- 3,46 g / l (p>0,05). CONCLUSIONS: The administration of
      oxytocin in the vein of the umbilical cord as a means of prevention of bleeding
      can be used to reduce the duration of the III stage of labor and the amount of
      blood loss.

PMID- 29059646
TI  - Kocuria rosea, kocuria kristinae, leuconostoc mesenteroides as caries-causing
      representatives of oral microflora.
AB  - INTRODUCTION: Recently, opportunistic microflora are increasingly known to be
      involved in the development of pathological processes in various systems and
      organs. This situation promotes interest in their detailed study as causative
      agents of bacterial infections. THE AIM: To study the microbial species residing
      in carious cavities in acute profound caries. MATERIALS AND METHODS: The study
      involved 14 people with a diagnosis of acute profound caries. Microbiological
      methods included determining species of microorganisms' cultures from carious
      cavities in acute profound caries. Final identification was carried out by
      automatic bacteriological analyzer Vitec-2compact bioMerieux. CONCLUSION: Among
      the bacteria isolated, Kocuria rosae, Kocuria kristinae, and Leuconostoc
      mesenteroides are the focus of the authors' attention due to their identification
      rate in the patients. These microbial species are little studied due to the lack
      of data on their cariogenic associations.The meticulous study of the
      microorganisms, isolated from carious cavities in patients with acute profound
      caries by automatic bacteriological analyzer Vitec-2 Systems bioMerieux, and
      findings on their biochemical properties allow us to conclude that Kocuria rosae,
      Kocuria kristinae, and Leuconostoc mesenteroides are among the microorganisms
      making up the microflora of carious cavities under acute profound caries and are
      involved in the development of the caries process.

PMID- 29059647
TI  - Monitoring of awareness level in dispensary patients with arterial hypertension.
AB  - INTRODUCTION: Results of monitoring of awareness level in dispensary patients
      with arterial hypertension (AH) are given in the article. The objective of the
      study was to investigate awareness level of dispensary patients with hypertension
      in Sumy as for the course of their disease, implementation of preventive
      measures, diagnosis and treatment, and to use the obtained information in the
      process of management of healthcare quality. MATERIALS AND METHODS: The results
      of close-ended questionnaires were used in the capacity of materials. A total of
      2019 patients were surveyed. RESULTS: Despite the high level of patients'
      awareness of AH course and possible complications, the survey showed insufficient
      level of their own responsibility for their health. CONCLUSIONS: The main reasons
      for poor adherence to doctor's recommendations are forgetfulness, lack of time,
      reluctance. Measures were developed to increase awareness level in patients with
      AH by means of strengthening awareness-raising activities and communications, as
      well as creation and implementation of effective targeted health-and-social
      programs.

PMID- 29059648
TI  - Determine the effectiveness of lipid-lowering therapy in patients with chronic
      obstructive pulmonary disease combined with coronary heart disease.
AB  - INTRODUCTION: In complex treatment of chronic obstructive pulmonary disease
      (COPD) combined with ischemic heart disease (IHD) more and more attention is
      drawn to pleiotropic effect of statins. The aim of our researches became
      determining the effectivity of utilization of rosuvastatin (CRESTOR(r), IPR
      PHARMACEUTICALS, Inc.) in complex treatment of COPD combined with IHD. MATERIALS
      AND METHODS: Basing on pulmonology department of Poltava regional clinical
      hospital, 30 patients with COPD combined with IHD have been examined (stable
      effort angina FC II) aged from 51 to 67 y.o. (average age was 57,03 +/- 3,51).
      The patients were divided into two age compatible groups. Patients of the main
      group (n = 15) underwent regular COPD and IHD treatment, addind 20 mg of
      rosuvastatin per night. The observed group (n = 15) didn't receive rosuvastatin.
      The examination of patients was held before and half year of treatment, included
      the estimation of respiratory symptoms of the disease, the degree of intensity of
      dyspnea (Medical Research Council Dyspnea Scale). The tolerance to physical
      exercise was studied with 6 minute walking test. The cholesterine level, HDL,
      LDL, function of ventilation have been tested as well. The average frequency of
      aggravations during the year was estimated through retrospective examination of
      anamnesis. RESULTS: After the treatment the improvement of clinical state has
      been noticed at both groups due to decrease of intensity of respiratory symptoms
      of the disease, such as cough, amount of expectoration, dyspnea and also increase
      of tolerance to physical exercise and improvement of laboratory-instrumental
      indexes. Though the patients of the main group were noticed to have significantly
      less amount of expectoration and cough. The distance covered in 6 minutes was
      positively longer (r < 0,05). It has to be noted that the patients of the main
      group had positive decrease of wheezing after treatment, due to increase of FEV1,
      GI (r < 0,01). The retrospective studying of the anamnesis revealed that the
      frequency of arrogations during the year was 1-2 times a year (1,6 +/- 0,48).
      CONCLUSIONS: Including rosuvastatin into the treatment scheme allows to decrease
      and stabilize the main clinical symptoms of this constellation of diseases,
      improving the quality of life, reduce the frequency of exacerbations.

PMID- 29059649
TI  - [The overall assessment of psychological well - being of patients with multiple
      sclerosis after the application of physical therapy. Part 2].
AB  - INTRODUCTION: Multiple sclerosis is a chronic demyelinating disease of the
      central nervous system, which results a progressive disability. The disease
      reduces the quality of life of patients, changes the general health perceptions,
      and also limits performing social roles because of emotional problems. THE AIM:
      Evaluation of the impact of the methods of rehabilitation to improve the mental
      health of patients with multiple sclerosis, and also to change individual
      parameters included in the overall assessment of mental health. MATERIAL AND
      METHODS: The study was conducted in 2010-2014 at the Department of Physical
      Medicine and Rehabilitation in Lodz. The study included 120 patients with
      multiple sclerosis. Patients were classified into 4 test groups: in the first was
      used the laser, in the second - laser and magnetostimulation, in the third -
      kinesiotherapy, and in the fourth - magnetostimulation. The tests were carried
      out three times. To evaluate the quality of life was used Quality of Life
      Questionnaire (MSQOL-54), analyzed the overall assessment of mental health.
      RESULTS: The improvement in a range of parameters, an overall assessment of the
      quality of mental health has allowed to get a better overall psychological well
      being. ,There was oserved a statistically significant difference at the level of
      p<0.001 between groups in 4/5 investigated parameters, statistically significant
      differences weren't obserwed at the evaluation of cognitive functions. The
      greatest improvement was observed in Group II and Group IV. CONCLUSIONS: In the
      examination it was confirmed an effectiveness of physical treatment, such a the
      laser radiation and magnetostimulation. Synergism of both methods in their
      biological activity, allows for evoke of hysteresis fenomenon, resulting in the
      maintenance of the treatment effects after cessation of rehabilitation. Applying
      the classical kinesiotherapy only doesn't allow to get long-term effects.

PMID- 29059650
TI  - [Large trade clusters as areas of intensified occurrences of states of rapid
      health worsening in Poland].
AB  - INTRODUCTION: In the modern world, people gather more increasingly in large
      clusters such as shopping centres, markets, cinema centres, operas, ferries,
      liners, recreation areas and resorts. Such clusters predispose to intensified
      occurrences of states of rapid health worsening and health hazard. THE AIM: The
      main aim is to indicate that in trade space, especially in municipal markets,
      states of rapid health worsening and health hazard appear, as well as to
      characterize the individual incidents and types of medical interventions.
      MATERIAL AND METHODS: The empirical material originates from the sheets of
      records of first-aid concerning life-saving actions, the nurse work register, as
      well as the security agency reports. Records of first-aid of events taking place
      during one selected weekend day, for 6 hours of highest population density,
      underwent a retrospective analysis. The analysis of the material was carried out
      in terms of reasons of interventions, in states of rapid health worsening and
      health hazard, as well as the frequency of calls of medical first-aid service.
      RESULTS: During 2011, there were approximately 100 such states in the municipal
      markets which underwent the study. In shopping centres there were 95% of such
      states. In each of the three analysed areas, the internal factors responsible for
      rapid health worsening constitute over 60%. Among interventions caused by a
      disease, states related to circulatory system and nervous system occurred most
      frequently. Big municipal market themselves are potential areas of an increased
      occurrence of states of rapid health worsening and health hazard. They can be
      compared to religious ceremonies described in the subject bibliography.
      CONCLUSIONS: Large trade spaces, especially municipal markets in city centres,
      generate a high risk of occurrences of states of rapid health worsening and
      health hazard, in comparison to shopping malls. The risk increases with the age
      of customers. The incidences related to sicknesses are the majority of
      interventions in trade areas.

PMID- 29059651
TI  - [The features of a functional state of the coronary circulation in women-smokers
      with non st elevation acute coronary syndrome].
AB  - INTRODUCTION: Acute coronary syndrome is one of the most adverse prognostic
      clinical forms of ischemic heart disease. In recent years, attention of
      researchers and cardiologists practical attract female patients due to a
      substantial increase in the prevalence including acute coronary syndrome,
      differences in the causes and features of its course. Women often diagnosed
      myocardial infarction without ST elevation and nonobstructive coronary heart
      disease associated with coronary spasm or stratification of coronary artery. The
      study of the pathophysiological mechanisms of myocardial infarction also showed
      the existence of certain gender differences. However, the available literature
      contains little data on the impact of smoking on morphological and functional
      condition of the coronary arteries in women with severe forms of coronary heart
      disease. AIM: to conduct contrastive analysis of coronary circulation state
      according to data of coronarography (CAG) in women with non ST elevation acute
      coronary syndrome. MATERIALS AND METHODS: 61 women aged 35-77 were examined
      (middle age 57, 9+/-1,2) who were hospitalized because of non ST elevation acute
      coronary syndrome. Depending on smoking habit all the patients of general group
      were divided into two subgroups. First subgroup (n=29, middle age 54,3+/-1,5)
      consisted of smoking women who had been smoking for 5 years >=5 cigarettes a day
      (an average number of smoked cigarettes per day was 9,8) Second subgroup (n=32,
      middle age 61,8+/-1,3) consisted of ill non-smoking women. We studied a type of
      coronary circulation? its nature, localization and evidence of coronary arteria
      damage and characteristics of microvascular and collateral blood flow. RESULTS:
      smoking women with non ST elevation acute coronary syndrome more often have
      bigger damages of coronary arteria: hemodynamically relevant and diffusive
      damages mostly located in proximal medial segments often with connected damage of
      distal segments especially of the left coronary arteria and its interventricular
      branch that causes a compensatory hypernormal development collateral blood flow
      and predominance of right blood supply type. Approximately 59,02% of women have
      sustainable violation of coronary microcirculation and myocardial perfusion,
      especially in cases of absence of coronary arteria hemodynamically relevant
      stenosis; much more often (by half) it is observed in smoking women (75,86%) that
      can be recognized on a coronarography as rather delayed blood flow and retention
      of contrast release. One-third of women occurs in the setting of almost unchanged
      coronary red vessels. CONCLUSION: durable smoking causes hard vessel damages with
      the occurrence of hemodynamic stenosis in proximal and medial segments of
      magistral coronary arteries, which are often connected with their distal
      (diffusive) changes and more frequent violation in microcirculation system.

PMID- 29059653
TI  - Blood motion: turbulent or laminar?
AB  - INTRODUCTION: The issue on the mode of blood motion in the bloodstream, where the
      arterial and venous flow is significantly different, has been of greater concern
      recently. However, the conclusions are largely based on the analysis of the
      geometric orientation in the wall of arteries of smooth muscle elements. The aim
      of our study was to examine the characteristics of the prominent configuration of
      cardial cavities and arterial vessels. MATERIALS AND METHODS: The material for
      study were specimens of human heart, rabbit aorta and arterial microvessels of
      rat salivary glands, examined by injection and corrosive methods, scanning and
      transmission electron microscopy. RESULTS: Specific attachments are to be
      involved to transform the laminar flow of blood into the turbulent one. We
      hypothesize that appendages in the atria and muscular trabeculae of heart in the
      ventricles with particular orientation to the bloodstream from the atria into the
      aorta and pulmonary trunk should be assigned to such attachments. The
      longitudinal axes of the auricles are at the right angle to the axial blood flow
      from the atria to the ventricles. Compound relief of the right auricle is caused
      by the pectineal muscles and compound relief of the left auricle by the coral
      like processes. Vortex flow is formed due to configuration of such relief in
      auricular systole, which is superimposed on the main bloodstream from the atria
      to the ventricles, making it turbulent. Ventricles of the heart, due to
      contractive activity of muscular trabeculae are the place of origination of
      vortex motion of blood in the initial parts of pulmonary and systemic
      circulations. Muscular trabeculae in the left ventricle have right-handed helical
      path with large slope of turns from the apex of the heart to its base, whereas in
      the right ventricle they are of left-handed flabelliform orientation from the
      cardiac apex to cardiac base. Such position suggests that the turbulence of blood
      flow, originating in the cardial cavities, is dictated by the need for even
      mixing of blood corpuscles while moving on the arteries. We believe that consumed
      energy could be enough for overcoming a resistance in the main arteries, in the
      wall of which there is a lack of active contraction elements. Intimal relief of
      the rabbit aorta is representad by the distinctly pronounced folds,
      longitudinally oriented on the steep spiral. They acquire especially steep
      (whirlpool or vortex) nature in the area of the opening into the intercostal
      arteries, which, as it is well known, in contrast to the aorta, are assigned into
      the arteries of the mixed type. Minor arterial microvessels (metarterioles-like
      type) have similar internal relief of the wall, which must extrude into the inner
      lumen of nuclear zones of endothelial cells. But the motion of blood in the
      arterial microvessels will greatly depend on the wave myogenic activity of smooth
      myocytes in their wall. Specific orientation of smooth muscle elements in the
      arterial microvessels is directed onto the formation of turbulent blood flow,
      contributing to its better mixing and ten-time increase in the intensity of
      metabolic processes. Sonclusion: The findings show that the conditions of
      hemodynamics in the great blood vessels suppose turbulent motion of blood that
      emerges in the cardial cavities, which is necessary for even mixing of blood
      corpuscles and their orderly distribution in homogeneous erythrocytic mass that
      would have been impossible in conditions of laminar motion of blood.

PMID- 29059652
TI  - Gerd: clinical solutions of problems in general practice.
AB  - INTRODUCTION: A systematic review of the results of 15 epidemiological studies
      showed that the prevalence of GERD in the population of Western Europe and North
      America is 10-20%. The frequency of GERD prevalence in the population is
      obviously higher than that according to the data of statistics, due to the fact
      that only a small amount of patients with heartburn apply for medical care, and
      the fact that not all doctors, especially general practitioners, devote
      sufficient attention to this problem. However, one of the features of modern
      clinical medicine is that diseases lose their mono- morbid character and more
      often becomes comorbid. THE AIM: To explore the features of acid production and
      level of acid influence in the stomach and esophagus in patients with isolated
      GERD, hypertension and their comorbidity. MATERIALS AND METHODS: For this study 4
      groups were selected: group of patients with GERD, a group of patients with
      hypertension, the group of patients with comorbid hypertension and GERD and group
      without GERD and hypertension (total 78 patients). To all the patients 3-channel
      gastro esophageal pH monitoring was performed. In our case, we conducted a 3-hour
      version of the survey with standardized provoking breakfast. All patients
      underwent assessment of gastric secretion by original integrative indicators that
      reflect basal pH, number of different types of refluxes, duration of alkalization
      in stomach after meal. RESULTS: GERD patients with hypertension and without are
      demonstrating an equal number of acid and all (nonacid + acid) reflux which is
      18.9 against 19,8 (p > 0.05). But the difference between the two groups was that
      in patients with concomitant hypertension longer refluxes 309.3 to 179,1 (p <
      0.05) were observed and the total acid exposure tends to be prolonged - 25.9 to
      20.9 (p > 0.05). Our analysis of the state of gastric secretion on the results of
      200-minute intra gastric pH monitoring, showed as expected more intensive acid in
      both groups of patients with GERD. The most "acidic" patients were GERD patients
      with hypertension, but compared with similar patients without hypertension, the
      difference was false due to the relatively small size of the samples. CONCLUSION:
      Comorbidity of GERD and hypertension is characterized by severe pathological
      dysmotility in the lower third of the esophagus, unlike isolated GERD, which
      affects the increase in acid exposure and susceptibility to long reflux. A factor
      that may add to burden of GERD in combination with hypertension may be gastric
      hyperacidity and a clear predisposition to obesity.

PMID- 29059654
TI  - [Hyperuricemia in obese patients with pharmacologically treated essential
      hypertension].
AB  - INTRODUCTION: Hyperuricemia and gout are a growing health problem worldwide.
      Their etiology is complex, and usually caused by excessive production of uric
      acid and/or impaired excretion. Some drugs used in the treatment of high blood
      pressure furthermore increase the risk of hyperuricemia. An additional risk
      factor for hyperuricemia is obesity. Thus far, there is no consensus on the
      treatment of patients with asymptomatic hyperuricemia, despite a large number of
      studies conducted worldwide. THE AIM: To evaluate the prevalence of hyperuricemia
      among patients with essential hypertension and obesity, pharmacologically treated
      with combination therapy. MATERIAL AND METHODS: A total of 109 obese patients
      (mean BMI=34.6+/-3.5 kg/m2) were included in this study, selected from the
      outpatients at the Clinic of Arterial Hypertension, the unit of the Cardinal
      Stefan Wyszynski Institute of Cardiology in Warsaw. Patients were treated with at
      least two antihypertensive drugs. Blood pressure, uric acid and insulin levels
      were measured among patients. RESULTS: The average systolic blood pressure and
      diastolic blood pressure were of 131+/-5,9 and 84.6+/-3.6 mmHg respectively, the
      average uric acid level of 6.4+/-1.5 mg/dl, and the average level of insulin
      17.6+/-11.0 mU/L. Hyperuricemia was found in 33 patients (27.5% of subjects). The
      uric acid level was significantly higher among men. A positive correlation
      between the serum uric acid concentration of serum insulin (r = 0.27, p <0.001),
      age (r = 0.21, p <0.002) and BMI patients (r = 0.26, p <0.002) has been shown.
      There were no significant differences in the concentration of uric acid among
      patients receiving multiple antihypertensive agents. CONCLUSION: The incidence of
      hyperuricemia demonstrated in this study confirms the findings of other authors
      and indicates a fairly common prevalence of this phenomenon among a population of
      patients with hypertension. Individually adjusted multidrug antihypertensive
      therapy does not seem to affect significantly the concentration of uric acid, but
      further research is needed in this respect.

PMID- 29059655
TI  - [analysis of adherence and compliance to methotrexate therapy in rheumatoid
      arthritis patients].
AB  - Rheumatoid arthritis is chronic inflammatory disease leading to disability and
      increasing the risk of premature death. Early treatment is crucial for remission
      and maintaining it for a maximal time. Adherence of the patient to the
      therapeutic recommendations is necessary. Although this issue is important, its
      role in achieving of therapeutic success is not fully noted by patients as well
      as medical stuff. Patients with RA are often non-adherent to rheumatologist's
      recommendations and non-compliance to the therapy regimen. The causes of this
      phenomenon are numerous and lie in the patient's attitude to therapy or are
      patient-independent. To effectively increase the level of adherence and
      compliance, the detailed medical care, including education of the patient, as
      well as adaptation of the drug form, by concentrating the active compound, is
      essential.

PMID- 29059656
TI  - Vat rates on medical devices: foreign experience and Ukrainian practice.
AB  - INTRODUCTION: In Ukraine differentiated VAT rates is a matter of debate. Today
      the Cabinet approved a list of medical products that has been changed three times
      resulting in changed VAT rates for specific products. European Union provides
      another method of regulation of VAT rates on medical devices. The abovementioned
      demonstrates the relevance of this study. MATERIAL AND METHODS: Comparative
      analysis of Ukrainian and European Union legislation based on dialectical,
      comparative, analytic, synthetic and comprehensive research methods were used in
      this article. DISCUSSION: In Ukraine general rate of VAT for all business
      activities is 20 %. But for medical devices, Tax Code of Ukraine provides special
      rules. VAT rate of 7% for transactions supplies into Ukraine and imported into
      the customs territory of Ukraine of medical products on the list approved by the
      Cabinet. The list generated by the medical product name and nomenclature code
      that does not correspond to European experience and Council Directive
      2006/112/EC. CONCLUSION: In our opinion, reduced VAT rates should to be
      established for all medical devices that are in a stream of commerce, have all
      necessary documents, that proved their quality and safety and fall under
      definition of medical devices.

PMID- 29059657
TI  - [The information-analytical provision of the analysis of the indicators of
      morbidity among children's population of Ukraine].
AB  - INTRODUCTION: Children's health is the future of the Ukrainian nation, the
      intellectual and labor potential of our society. The study of the state of health
      of the child population, the identification of features and trends in different
      age groups, in different areas of residence makes it possible to identify
      priority problems and determine the policy of prevention. The aim: The study of
      the health indicators of the child population, the specifics of the formation of
      data on the health of children and adolescents, the identification of the
      appropriateness of recording and analyzing the risk factors for the occurrence of
      the most common diseases. MATERIALS AND METHODS: To achieve this goal, the annual
      reports (f.12, f.20, f.21-a, f.31, f.70) were analyzed, the records of medical
      institutions were analyzed. RESULTS: With a decrease in the number of children,
      the rates of morbidity and prevalence remain quite high. The increase in the
      incidence of general morbidity is due to the accumulation of chronic diseases and
      is confirmed by the age-related dynamics of the incidence of diseases newly
      diagnosed, among all those registered: among children from 0 to 6, 87.0%; Among 7
      14 years old - 67.3%; Among adolescents - 57.06%. CONCLUSIONS: When monitoring
      the state of children's health, it is advisable to determine not only the
      structure of the incidence, but the main risk factors for each age group in
      general, and certain groups of diseases in particular, and thus predict the level
      of public health in order to create preventive measures in advance.

PMID- 29059658
TI  - Road safety in Poland: magnitude, causes and injuries.
AB  - Road accidents are a serious problem of the modern world. They are one of the
      main causes of injuries and are the third most frequent cause of death. Every
      year, about one million people, adults and children, die on the roads and several
      millions get injured. Mortality rate due to injuries from road accidents amounts
      to 2.2% of all deaths in the world. The research presents epidemiology of road
      accidents in the period 2004-2015 with particular emphasis on the key issues of
      road safety in Poland, related to the dangerous behaviour of road users
      (disregard toward traffic rules). Between years 2004 and 2015 on Polish roads
      took place more than 508000 accidents with 53155 fatalities and more then 572000
      casualties. Despite the various measures which are taken to improve safety on
      Polish roads, the number of dead and wounded in the vehicle mishap is still
      large, and losses borne by society are high. To improve safety on Polish roads,
      it is necessary to continue multi- action plan to systematically progress in the
      level of road safety.

PMID- 29059659
TI  - [Post-stroke spasticity management including a chosen physiotherapeutic methods
      and improvements in motor control - review of the current scientific evidence.]
AB  - Cerebrovascular diseases based on stroke etiology concern millions of people
      worldwide, and annual rates of disease are still increasing. In the era of an
      aging society and suffering from a number of risk factors, in particular those
      modifiable, strokes and muscles' spastic paresis, subsequently resulting in
      damage of upper motor neuron structures will become a serious problem for the
      entire health care system. Effective management and physiotherapy treatment for
      post-stroke spasticity persisted, both in the acute and chronic, is still a
      significant medical problem in the interdisciplinary aspect. Care procedures for
      this type of patient becomes a kind of challenge for specialists in neurology,
      internal medicine, cardiology, dermatology or neurosurgery, but also for
      physiotherapists in their everyday clinical practice. The aim of this paper is to
      present the issues of cerebral stroke and resulting spastic hypertonia in terms
      of current pharmacological treatment and surgery, and primarily through the use
      of effective physiotherapy methods, the use of which was confirmed in the way of
      reliable scientific research in accordance with the principles of Evidence Based
      Medicine and Physiotherapy (EBMP).

PMID- 29059660
TI  - Legal restraints of pesticide effect on human organism and environment under
      international legislation.
AB  - INTRODUCTION: Human health depends on many factors: a level of medicine, quality
      of medical preparations, state of the environment, food safety, lifestyle and
      others. Phytosanitary products including pesticides used by farmers to kill,
      control reproduction and prevent animal, microbial or plant pests in the
      cultivation of agricultural products, which are the basis of human food, are one
      of the factors that may have an unfavourable effect on human health. AIM: To
      analyze provisions of international legislation for presence of effective means
      to prevent a negative pesticide effect on human health and the environment.
      MATERIALS AND METHODS: International acts, data of international organizations
      and conclusions of scientists have been examined and used in the study. The
      article also summarizes information from scientific journals and monographs from
      a medical and legal point of view with scientific methods. As a part of a
      systematic approach, issues of the pesticide effect in the course of their use on
      human health and the environment are analyzed. RESULTS: Based on the undertaken
      study, it has been found that developed countries take much better care of
      prevention and reduction of the negative pesticide effect on human health and the
      environment in the course of their use than developing countries. CONCLUSIONS:
      The pesticide effect has a dual nature. On the one hand, it is positive to ensure
      efficient development of agriculture, but on the other hand, it is negative that
      is expressed in potential possibilities of harm to humans and the environment.

PMID- 29059661
TI  - [Constipation - natural methods of the treatment with regard to physiotherapeutic
      procedures].
AB  - The constipations belong to the most frequent intestinal dyspepsia ailments in
      the industrialized populations. Alimentary canal answers for the correct
      admission and digesting foods, their absorption and dismissing. In case of
      disorders relating dismissing the names a constipation, discomfort in everyday
      life constrain ill's to modification style of life and nourishing, as well as the
      frequent contact with a doctor or the specialist medical care. The etiology of
      constipations stool is multifactorial, what requires multidirectional therapeutic
      conduction. The name of constipation is dismissing of stool defines (seldom than
      3 days), be unusually the made difficult of act defecation connected with the
      presence sale hard and compact stool. Not infrequently the dismissing of
      incomplete evacuation lace-up by ill with feeling of dysfunction. The
      constipations most often step out in relationship with excessive contractibility
      of intestine - spastic constipations, be with reason of excessive atony of
      intestine - atonic constipations where sale weak peristalsis is the creature of
      constipations. In this work was the selected non - pharmacological methods in the
      treatment of constipation with regard a physiotherapeutic conduct introduced.

PMID- 29059662
TI  - [Euthyroid sick syndrome: an important clinical problem].
AB  - Despite absence of thyroid disease, patients with non-thyroidal illness
      frequently have changes in serum thyroid hormone measurements that may suggest
      thyroid dysfunction. These abnormalities include low serum triiodothyronine, high
      reverse triiodothyronine and usually normal or inappropriately low thyrotropin
      and thyroxine levels. The degree of thyroid function impairment correlates with
      disease severity and low levels of thyroid hormones, particularly thyroxine,
      predict a poor prognosis. Considerable controversy exists on whether the fall in
      thyroid hormone levels is adaptive and simply a normal, physiologic response to
      conserve energy, or whether it is maladaptive and requires treatment.
      Interpretation of thyroid function tests in the critically ill patient can be
      difficult and differential diagnosis of euthyroid sick syndrome is challenging,
      particularly in patients in whom no test results from before the onset of a
      critical illness are available. In recent years, some questions associated with
      euthyroid sick syndrome have been better understood. The purpose of this article
      is to review the present state of knowledge on the pathogenesis, diagnosis and
      clinical consequences of euthyroid sick syndrome to discuss pros and cons of its
      treatment.

PMID- 29059663
TI  - [Current issues in etiology, diagnostics and management in pulmonary
      hypertension].
AB  - Pulmonary hypertension (PH) is a pathophysiological disorder that may involve
      multiple clinical conditions characterizing with by an abnormal increase in mean
      pulmonary arterial pressure. It is a rare, debilitating disease with a poor
      prognosis. Despite significant progress in diagnosis and management, including
      disease-targeted therapies as well as development of specialized centres, PH
      remains a chronic disease without a cure. If untreated, it leads to right heart
      failure and premature death, and a multifactorial pathomechanism impacts
      negatively on further prognosis. Insufficient social awareness or non-specific
      initial symptoms accompany to delayed diagnosis and specialist treatment. In the
      following pages, we will review the currently classification, etiology as well as
      and diagnostic algorithms in PH. We discuss approved treatments, especially
      specific dug therapy for pulmonary arterial hypertension, and recently approved
      strategies for its refund. We also summarize the general measures for patients
      and their caregivers, as well as the role of support groups, and specialized
      centers in Poland.

PMID- 29059664
TI  - [guidelines for HIV testing in Poland].
AB  - Including HIV disease in the differential diagnosis is the responsibility of the
      treating physician. Unfortunately, despite 35 years passed from the description
      of the first cases of Acquired Immune Deficiency Syndrome, AIDS testing for HIV
      is offered sporadically in Poland. The aim of this paper is to present the
      current recommendations for HIV testing.

PMID- 29059665
TI  - [Dyspnea in a patient after open reduction of fracture of the femur].
AB  - Acute dyspnoea in the postoperative period requires quick consideration of all
      possible causes and implementation of the proper treatment. During the
      differential diagnostic process, other than the most common cardio-pneumological
      and otolaryngological reasons, we should consider a whole array of rare causes
      such as neuromuscular illnesses, renal failure, and gastrointestinal diseases.
      This case is an example of sudden onset of dyspnoea presenting in a 67 year old
      woman with COPD. The dyspnoea occurred in first postoperative day after open
      reduction of fracture of the femur. Onset of respiratory insufficiency symptoms
      and circulatory instability appeared suddenly and advanced quickly, as result of
      a large Morgagni type retrosternal hernia, requiring urgent thoraco-surgical
      intervention. In the long term, the effects of this operation were very good.

PMID- 29059666
TI  - [Interdisciplinary surgical and prosthetic treatment of adenocarcinoma of the
      palate].
AB  - INTRODUCTION: The palatal mucosa requires careful testing prior to prosthetic
      treatment. Pathological changes may occur during the period of use of a dental
      prosthetic, especially when worn constantly. Aim of the report: We describe the
      case of a patient who experienced extensive changes in the mucosa of the hard
      palate over 12 years of dentures used. CASE PRESENTATION: The 78-year-old female
      patient was referred to the Department of Otolaryngology of the Jagiellonian
      University Hospital in Krakow with a diagnosis of adenocarcinoma of the palate.
      In connection with the planned extensive surgery, there was indication for the
      use of a palatal plate with an obturator in order to close the expected gap in
      the palate structure. No recurrence of the tumor was seen in the period examined.
      Summation: Despite the extensive tumor, two small defects in the palate remained
      after surgery. These were effectively sealed and the patient reached the five
      year survival point.

PMID- 29059667
TI  - [Life-saving cricothyroidotomy in throat and laryngeal injuries - case study].
AB  - The percentage of laryngeal injuries managed by hospital emergency departments is
      low. Currently, with the Emergency Medical Services working more efficiently,
      diagnostic imaging tools being more available and more precise surgical
      procedures after the injury, the mortality and disability rate among trauma
      victims is systematically decreasing. The given paper presents a case of a
      multiple organ trauma, including trauma to the larynx and throat, experienced
      during agricultural works. Life-saving surgical cricothyroidotomy using a
      tracheal tube was performed after preliminary diagnosis of the patient. This
      procedure, despite extensive traumatic injuries to the airways, led to airway
      management, patient stabilization and allowed to perform further diagnostic and
      therapeutic procedures.

PMID- 29059668
TI  - [Early complications of extracorporeal rewarming].
AB  - BACKGROUND: Application of appropriate method of rewarming is the key issue in
      the management of hypothermia. Severely hypothermic, life-threatened patients
      require advanced extracorporeal rewarming. Such procedure is not free of possible
      complications, yet, if the qualification for extracorporeal rewarming is correct,
      it guarantees restoration of hemodynamic stability, and what is the most
      important, leads to full neurologic recovery, even with long resuscitation times.
      THE AIM: The summary of complications observed during extracorporeal rewarming
      with ECMO in severely hypothermic patients and analysis of their prevalence in
      managed group. Presentation of possible etiology and means of prevention of
      anticipated complications and suggested strategies of their treatment. MATERIALS
      AND METHODS: Retrospective analysis of medical records of all 33 patients with
      severe accidental hypothermia, accepted for extracorporeal rewarming with
      venoarterial ECMO. CONCLUSIONS: Based on reviewed medical records of severely
      hypothermic patients subjected to extracorporeal rewarming it was possible to
      identify these complications of management, that are hypothermia related, and
      which are not to be seen in patients treated with ECMO for other reasons.

PMID- 29059669
TI  - Clinical investigation of the Nucleus Slim Modiolar Electrode.
AB  - AIMS: The Nucleus CI532 cochlear implant incorporates a new precurved electrode
      array, i.e., the Slim Modiolar electrode (SME), which is designed to bring
      electrode contacts close to the medial wall of the cochlea while avoiding trauma
      due to scalar dislocation or contact with the lateral wall during insertion. The
      primary aim of this prospective study was to determine the final position of the
      electrode array in clinical cases as evaluated using flat-panel volume computed
      tomography. METHODS: Forty-five adult candidates for unilateral cochlear
      implantation were recruited from 8 centers. Eleven surgeons attended a temporal
      bone workshop and received further training with a transparent plastic cochlear
      model just prior to the first surgery. Feedback on the surgical approach and use
      of the SME was collected via a questionnaire for each case. Computed tomography
      of the temporal bone was performed postoperatively using flat-panel digital
      volume tomography or cone beam systems. The primary measure was the final scalar
      position of the SME (completely in scala tympani or not). Secondly, medial
      lateral position and insertion depth were evaluated. RESULTS: Forty-four subjects
      received a CI532. The SME was located completely in scala tympani for all
      subjects. Pure round window (44% of the cases), extended round window (22%), and
      inferior and/or anterior cochleostomy (34%) approaches were successful across
      surgeons and cases. The SME was generally positioned close to the modiolus.
      Overinsertion of the array past the first marker tended to push the basal
      contacts towards the lateral wall and served only to increase the insertion depth
      of the first electrode contact without increasing the insertion depth of the most
      apical electrode. Complications were limited to tip fold-overs encountered in 2
      subjects; both were attributed to surgical error, with both reimplanted
      successfully. CONCLUSIONS: The new Nucleus CI532 cochlear implant with SME
      achieved the design goal of producing little or no trauma as indicated by
      consistent scala tympani placement. Surgeons should be carefully trained to use
      the new deployment method such that tip fold-overs and over insertion may be
      avoided.

PMID- 29059670
TI  - The Impact of Cysteine-Rich Intestinal Protein 1 (CRIP1) on Thyroid Carcinoma.
AB  - BACKGROUND/AIMS: CRIP1 (cysteine-rich intestinal protein 1) has been found in
      several tumor types; however, its prognostic impact and role in cellular
      processes, particularly in thyroid carcinoma, are still unclear. METHODS: To
      elucidate the prognostic impact of CRIP1, we analyzed tissues from 58 primary
      invasive thyroid carcinomas using immunohistochemistry. Western blotting was
      performed to investigate CRIP1 protein expression in the thyrocyte cell line Nthy
      ori 3-1 and four different thyroid carcinoma cell lines, K1, TPC-1, TT, and
      SW579. Endogenous expression of CRIP1 was suppressed using a siRNA (si-CRIP1).
      The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used
      to investigate cell viability. Flow cytometric analysis was used to detect cell
      cycle progression and cell apoptosis. The effects of silencing CRIP1 on cell
      migration and invasion were detected using the transwell assay. RESULTS: The
      immunohistochemistry results showed that CRIP1 was overexpressed in thyroid
      carcinoma. CRIP1 expression was associated with tumor size, TNM stage, and
      lymphatic metastasis, but not with age, gender, and tumor location. In addition,
      the expression of CRIP1 in K1, TPC-1, TT, and SW529 cells was higher than that in
      the Nthy-ori 3-1 cells. The highest expression was observed in the SW579 and TT
      cells. Furthermore, silencing CRIP1 inhibited the proliferation, migration, and
      invasion of thyroid carcinoma cell lines SW579 and TT. We also found that
      silencing CRIP1 induced G1 arrest and apoptosis of thyroid carcinoma cell lines
      SW579 and TT. CONCLUSION: In conclusion, CRIP1 acts as an oncogene in the cell
      proliferation, migration, and invasion processes of thyroid carcinoma. CRIP1 may
      serve well as an independent prognostic marker with significant predictive power
      for use in thyroid carcinoma therapy.

PMID- 29059671
TI  - Polymorphisms in Sex Hormone Metabolism Genes and Risk of Preeclampsia in
      Taiyuan, China.
AB  - OBJECTIVE: Aberrant synthesis and metabolism of sex hormone are likely to be
      associated with alterations in vascular function in preeclampsia (PE). The study
      aims to investigate whether single nucleotide polymorphisms (SNPs) in sex hormone
      related genes are associated with PE. METHOD: We performed a nested case-control
      study including 436 pregnant women (203 PE and 233 healthy or normal pregnant
      women) to investigate associations between 96 SNPs in 28 sex hormone-related
      genes and risk of PE. RESULTS: TXNRD2/COMT rs3788314 and SULT1A2/SULT1A1
      rs4788073 were associated with an increased risk of PE overall (ptrend = 0.004
      and 0.003, respectively), early-onset PE (ptrend = 0.007 and 0.009,
      respectively), and severe PE (ptrend = 0.002 and 0.005, respectively).
      Additionally, CYP17A1 rs4919690 and rs4919687 and LHCGR rs10180731 were
      associated with an increased risk of severe PE (ptrend = 0.005, 0.006, and 0.014,
      respectively), while GNRHR rs2630488 was associated with a decreased risk of
      severe PE (ptrend = 0.014). We also observed that HSD17B3 rs8190512 was
      associated with a decreased risk of early-onset PE (ptrend = 0.003). We observed
      strong linkage disequilibrium in SULF1 (rs10106958, rs7813987, and rs6990375).
      CONCLUSIONS: Our study suggested that genetic polymorphisms in TXNRD2/COMT,
      SULT1A2/SULT1A1, CYP17A1, HSD17B3, GNRHR, LHCGR, and SULF1 might play a role in
      PE, especially in early-onset PE and severe PE. Future studies are warranted to
      replicate the observed associations and their functional mechanisms.

PMID- 29059672
TI  - Lack of Association between BMP2/DLX3 Gene Polymorphisms and Dental Caries in
      Primary and Permanent Dentitions.
AB  - The aim of this study was to analyze the association between BMP2 (rs1884302) and
      DLX3 (rs2278163) gene polymorphisms and dental caries in primary and permanent
      dentitions. A total of 914 subjects were genotyped by the TaqMan methods: 176
      caries-free children (with Decayed/Missing/Filled Teeth, DMFT = 0), 542 patients
      with dental caries in permanent dentition (DMFT >=1), 83 caries-free children
      with primary teeth (with decayed/missing/filled teeth, dmft = 0), and 113
      children with early childhood caries (ECC, dmft >=1). There were no significant
      differences in allele/genotype frequencies between patients with caries in
      permanent dentition/ECC and caries-free children or between patients with very
      low (DMFT = 0-2), low (DMFT = 3-5), moderate (DMFT = 6-8), or high (DMFT >=9)
      caries experience. Variability in BMP2 and DLX3 was not associated with caries in
      the Czech population.

PMID- 29059673
TI  - Efficacy of Buffered Hypertonic Saline Nasal Irrigation for Nasal Symptoms in
      Children with Seasonal Allergic Rhinitis: A Randomized Controlled Trial.
AB  - BACKGROUND: Saline nasal irrigation is labelled as an add-on treatment in
      patients with allergic rhinitis (AR). The primary aim of this study was to
      compare the efficacy of 21-day use of buffered hypertonic saline (BHS) versus
      normal saline solution (NSS) on reducing nasal symptoms in children with seasonal
      AR (SAR). Comparing their efficacy on nasal cytology counts (NCC), quality of
      life, and sleep quality was the secondary aim. METHODS: In this 21-day, open
      label, randomized controlled study, 36 SAR children (aged 6-13 years) with a
      Total 5 Symptom Score (T5SS) >=5 received twice-daily BHS or NSS delivered
      through a nasal douche. Efficacy measures were least square mean changes (LSmc)
      in T5SS, NCC, Paediatric Rhinoconjunctivitis Quality of Life Questionnaire
      (PRQLQ), and Pittsburgh Sleep Quality Index (PSQI) scores. RESULTS: BHS improved
      the T5SS total score to a greater extent than NSS (LSmc -6.45 vs. -5.45, p <
      0.001). Concerning NCC, BHS significantly reduced the scores of neutrophils (LSmc
      -0.76, p = 0.004) and eosinophils (LSmc -0.46, p = 0.018), while NSS did not.
      Similarly, only BHS yielded a significant improvement in the PRQLQ score (LSmc 
      0.57, p = 0.009), whereas the improvement in PSQI score was comparable between
      the BHS (LSmc -0.77, p = 0.025) and NSS (LSmc -1.39, p < 0.001) groups. Overall,
      BHS was well tolerated. CONCLUSIONS: In children with SAR, BHS is effective in
      improving nasal symptoms and NCC, with an associated beneficial effect on quality
      of life.

PMID- 29059674
TI  - Chromosome Banding in Amphibia. XXXV. Highly Mobile Nucleolus Organizing Regions
      in Craugastor fitzingeri (Anura, Craugastoridae).
AB  - A 7-year cytogenetic study on the leaf litter frog Craugastor fitzingeri from
      Costa Rica and Panama revealed the existence of highly mobile nucleolus
      organizing regions (NORs) in their genomes. Silver (Ag)-staining of the active
      NORs demonstrated an exceptional interindividual pattern of NOR distribution at
      the telomeres of the chromosomes. All individuals examined showed a different and
      specific NOR location in their karyotypes. Furthermore, intraindividual variation
      in the NOR sites was found. This observation suggested the existence of mobile
      NORs in C. fitzingeri. Confirmation of this phenomenon was possible by systematic
      FISH analysis using an 18S + 28S rDNA probe. The extremely variable number and
      position of the NORs in C. fitzingeri is best explained by highly mobile NORs
      that move freely between the telomeres of the chromosomes. These transpositions
      must occur preferentially in premeiotic, meiotic, or postmeiotic stages, but also
      at a lower incidence in the somatic tissues of the animals. It is hypothesized
      that transposable (mobile) elements are closely linked to the NORs or are
      inserted into the major 18S + 28S rDNA spacers of C. fitzingeri. When such
      transposable elements spread by transpositions, they can carry with them complete
      or partial NORs. The present study provides detailed information on various
      differential chromosome banding techniques, in situ hybridization experiments,
      chromosomal hypermethylation patterns, determination of the genome size, and
      analyses of restriction fragment length polymorphisms of the DNA.

PMID- 29059675
TI  - Nasonia Parasitic Wasps Escape from Haller's Rule by Diphasic, Partially
      Isometric Brain-Body Size Scaling and Selective Neuropil Adaptations.
AB  - Haller's rule states that brains scale allometrically with body size in all
      animals, meaning that relative brain size increases with decreasing body size.
      This rule applies both on inter- and intraspecific comparisons. Only 1 species,
      the extremely small parasitic wasp Trichogramma evanescens, is known as an
      exception and shows an isometric brain-body size relation in an intraspecific
      comparison between differently sized individuals. Here, we investigated if such
      an isometric brain-body size relationship also occurs in an intraspecific
      comparison with a slightly larger parasitic wasp, Nasonia vitripennis, a species
      that may vary 10-fold in body weight upon differences in levels of scramble
      competition during larval development. We show that Nasonia exhibits diphasic
      brain-body size scaling: larger wasps scale allometrically, following Haller's
      rule, whereas the smallest wasps show isometric scaling. Brains of smaller wasps
      are, therefore, smaller than expected and we hypothesized that this may lead to
      adaptations in brain architecture. Volumetric analysis of neuropil composition
      revealed that wasps of different sizes differed in relative volume of multiple
      neuropils. The optic lobes and mushroom bodies in particular were smaller in the
      smallest wasps. Furthermore, smaller brains had a relatively smaller total
      neuropil volume and larger cellular rind than large brains. These changes in
      relative brain size and brain architecture suggest that the energetic constraints
      on brain tissue outweigh specific cognitive requirements in small Nasonia wasps.

PMID- 29059677
TI  - Parasitic Hematuria: Six Cases in a Row in a Single Centre in Spain.
AB  - Most cases of urogenital parasitosis are registered in Africa. However, migration
      movements and travellers moving from developed to developing countries are
      responsible for leading to an increased incidence of genitourinary infections
      caused by parasites in the western world including Spain having serious economic
      and health implications. The importance of its early detection and treatment also
      results from its potential risk for infertility, susceptibility for HIV infection
      and the development of bladder cancer. The most common presentation symptom is
      terminal haematuria, and when diagnosed, praziquantel is the treatment of choice.
      We report a series of 6 cases of urinary schistosomiasis that happened in a
      single centre in Spain and reminds the importance of having the infection in mind
      in certain cases of haematuria study.

PMID- 29059676
TI  - The Androgen Receptor Promotes Cellular Proliferation by Suppression of G-Protein
      Coupled Estrogen Receptor Signaling in Triple-Negative Breast Cancer.
AB  - BACKGROUND/AIMS: The targeted therapy for triple-negative breast cancer (TNBC) is
      still challenging due to poor understanding on its molecular etiology. The
      androgen receptor (AR) has recently emerged as a prognostic and treatment
      predictive marker in breast cancer. However, the role of AR in TNBC remained
      elusive. METHODS: Immunohistochemistry (IHC) was used to detect AR and G-protein
      coupled estrogen receptor (GPER) expression in tissue microarrays of 165 TNBC
      patients. Microarray analysis of mRNAs was performed to identify downstream
      regulators of AR. TNBC cells were cultured with dihydrotestosterone (DHT) alone
      or in combination with AR knockdown performed with AR shRNA. Cell viability and
      colony formation were assessed. Western blotting and qRT-PCR were used to examine
      protein and mRNA expression, respectively. The potential mechanism of AR-mediated
      GPER suppression was identified by Chromatin immunoprecipitation (ChIP) assay. AR
      and GPER expressions were also assessed in nude mouse xenografts by IHC. RESULTS:
      IHC staining showed that the expression of AR was positively associated with
      tumor size, lymph node metastasis and high-grade tumor in TNBC patients. AR
      activation triggered by DHT suppressed GPER expression, to promote cell growth of
      TNBC. G-1, a GPER agonist, inhibited DHT-stimulated proliferation. Further
      experiments illustrated that AR suppressed GPER activation via binding directly
      to the promoter of GPER. Moreover, a negative correlation between AR and GPER was
      observed in MDA-MB-231 tumor cell xenografts and TNBC patient samples.
      CONCLUSIONS: The suppression of GPER via AR may be involved in the positive
      actions towards the TNBC progression, making it a promising therapeutic target
      for TNBC treatment.

PMID- 29059678
TI  - Endocan: A Novel Marker of Endothelial Dysfunction in C1-Inhibitor-Deficient
      Hereditary Angioedema.
AB  - BACKGROUND: Hereditary angioedema (HAE) related to C1-inhibitor deficiency is a
      rare autosomal dominant disorder. Vascular cell adhesion molecules (VCAM) are
      known as endothelial activation markers. Endocan (also called ESM-1) is proposed
      as an endothelial dysfunction indicator. We aimed to investigate endothelial
      activation in attack-free periods in HAE patients by measuring their levels of
      endocan and VCAM-1. METHODS: Twenty-six HAE patients (22 female, mean age 40 +/-
      13 years) and 38 healthy control patients (13 female, mean age 36.9 +/- 12 years)
      were included in the study. Peripheral blood samples were collected from HAE
      patients during symptom-free periods and control subjects. Endocan and VCAM-1
      levels were measured using the enzyme-linked immunosorbent assay method. RESULTS:
      The median serum levels of endocan (647 +/- 101 ng/mL) and VCAM-1 (500 +/- 79
      ng/mL) in the HAE patients were significantly higher than in the control patients
      (391 +/- 41 and 325 +/- 4; p < 0.001 for both). CONCLUSION: The increased endocan
      and VCAM-1 levels may reflect an endothelial activation even in attack-free
      periods in HAE patients.

PMID- 29059679
TI  - Cannabinoids Regulate the Diameter of Pericyte-Containing Retinal Capillaries in
      Rats.
AB  - BACKGROUND/AIMS: Cannabinoids are vasoactive substances that act as key
      regulators of arterial tone in the blood vessels supplying peripheral tissues and
      the central nervous system. We therefore investigated the effect of cannabinoids
      on retinal capillaries and pericytes. METHODS: The effects of cannabinoids on
      capillary diameters were determined using an ex vivo whole-mount rat retinal
      model. Western blotting, quantitative PCR, and immunohistochemistry were
      performed to explore the underlying mechanism. RESULTS: Endogenous cannabinoid 2
      arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2)
      dilated the noradrenaline-precontracted capillaries in a concentration-dependent
      manner (1 uM to 0.1 mM). The extent of vasorelaxation was positively correlated
      with changes in pericyte width. The effects of R-(+)-WIN55212-2 on vasorelaxation
      and pericyte width were inhibited by a cannabinoid receptor type-1 (CB1)
      antagonist, AM251 or rimonabant (SR141716A), the nitric oxide synthase inhibitor
      l-NAME, and the guanylate cyclase inhibitor ODQ. They were also abolished by the
      removal of the endothelium, but not by the cannabinoid receptor-2 antagonist
      SR144528, the endothelial cannabinoid receptor antagonist O-1918, or the
      cyclooxygenase inhibitor indomethacin. CONCLUSION: The exogenous cannabinoid R
      (+)-WIN55212-2 promotes the vasorelaxation of pericyte-containing rat retinal
      capillaries. This effect of R-(+)-WIN55212-2 is dependent on CB1 and the nitric
      oxide-cyclic guanosine monophosphate pathway, and requires an intact endothelium.

PMID- 29059680
TI  - Altered Biological Properties in Dp71 Over-Expressing HBE Cells.
AB  - BACKGROUND/AIMS: In order to further characterize the biological traits of Dp71,
      HBE over expressing two most abundantly expressed Dp71 spliced isoforms, Dp71d
      and Dp71f, were established and their biological traits were explored. METHODS:
      The proliferation, migration and invasion capabilities of HBE-Dp71d and HBE-Dp71f
      cells were evaluated by MTT, colony formation, transwell and scratch assay. Cell
      cycle and apoptosis induced by H2O2 were measured by flow cytometer. Co-IP was
      performed to prove the interaction between lamin B1, FAK and Dp71. Western blot
      was performed to detect lamin B1, FAK, ERK and Cyclin D expression in HBE-Dp71d
      and HBE-Dp71f cells. RESULTS: HBE-Dp71d and HBE-Dp71f cells proliferated faster
      than their mock and blank controls; shortened their G0/G1 phase; enhanced their
      invasion and migration capabilities; reduced their apoptosis induced by H2O2. Co
      IP proved Dp71 directly interacting with focal adhesion kinase (FAK) and lamin B1
      in HBE cells. Increased lamin B1, FAK mRNA and protein expression, over
      activation of integrin/focal adhesion kinase/extracellular signal-regulated
      kinase (ERK)/cyclin D pathway were observed in HBE-Dp71d and HBE-Dp71f cells.
      CONCLUSIONS: Via increasing FAK in the cytoplasmic FAK-Dp71 , lamin B1 of nucleus
      laminB1-Dp71 complex, HBE-Dp71d and HBE-Dp71f cells alter their proliferation,
      migration, invasion, cell cycle and apoptosis rate induced by H2O2.

PMID- 29059681
TI  - Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in
      Zebrafish.
AB  - BACKGROUND/AIMS: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in
      traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and
      oedema. Antibacterial and anti-inflammatory activities have been reported for
      phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro.
      However, the underlying mechanisms in vivo remain poorly defined. In this study,
      we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS
      induced neutrophil inflammation by suppressing the MyD88-dependent signalling
      pathway in zebrafish. METHODS: LPS-yolk microinjection was used to induce a
      lethal LPS-infected zebrafish model. The effect of PHN on the survival of
      zebrafish challenged with lethal LPS was evaluated using survival analysis. The
      effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking
      neutrophils with a transgenic line. The effects of PHN on neutrophil production
      and migration were analysed by SB+ cell counts during consecutive hours after
      modelling. Additionally, key cytokines and members of the MyD88 signalling
      pathway that are involved in inflammatory response were detected using
      quantitative RT-PCR. To assess gene expression changes during consecutive hours
      after modelling, the IL-1beta, IL-6, TNF-alpha, MyD88, TRIF, ERK1/2, JNK,
      IkappaBa and NF-kappaB expression levels were measured. RESULTS: PHN could
      protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as
      indicated by decreased neutrophil infltration, reduced tissue necrosis and
      increased survival rates. Up-regulated IL-1beta, IL-6 and TNF-alpha expression
      also showed the same tendencies of depression by PHN. Critically, PHN
      significantly inhibited the LPS-induced activation of MyD88, IkappaBa, and NF
      kappaB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS
      stimulated zebrafish. Additionally, PHN regulated the MyD88/IkappaBalpha/NF
      kappaB signalling pathway by controlling IkappaBalpha, IL-1beta, IL-6, and TNF
      alpha expression. CONCLUSION: This study provides a rationale for the clinical
      application of PHN as an anti-inflammatory agent.

PMID- 29059682
TI  - Locomotor speed control circuits in the caudal brainstem.
AB  - Locomotion is a universal behaviour that provides animals with the ability to
      move between places. Classical experiments have used electrical microstimulation
      to identify brain regions that promote locomotion, but the identity of neurons
      that act as key intermediaries between higher motor planning centres and
      executive circuits in the spinal cord has remained controversial. Here we show
      that the mouse caudal brainstem encompasses functionally heterogeneous neuronal
      subpopulations that have differential effects on locomotion. These subpopulations
      are distinguishable by location, neurotransmitter identity and connectivity.
      Notably, glutamatergic neurons within the lateral paragigantocellular nucleus
      (LPGi), a small subregion in the caudal brainstem, are essential to support high
      speed locomotion, and can positively tune locomotor speed through inputs from
      glutamatergic neurons of the upstream midbrain locomotor region. By contrast,
      glycinergic inhibitory neurons can induce different forms of behavioural arrest
      mapping onto distinct caudal brainstem regions. Anatomically, descending pathways
      of glutamatergic and glycinergic LPGi subpopulations communicate with distinct
      effector circuits in the spinal cord. Our results reveal that behaviourally
      opposing locomotor functions in the caudal brainstem were historically masked by
      the unexposed diversity of intermingled neuronal subpopulations. We demonstrate
      how specific brainstem neuron populations represent essential substrates to
      implement key parameters in the execution of motor programs.

PMID- 29059684
TI  - Public Opinion About the Relationship Between Firearm Availability and Suicide:
      Results From a National Survey.

PMID- 29059685
TI  - Rethinking Rates of Undiagnosed Diabetes: The Value of a Confirmatory Test.

PMID- 29059686
TI  - Firearm Injury After Gun Shows: Evidence to Gauge the Potential Impact of
      Regulatory Interventions.

PMID- 29059687
TI  - Synopsis of the 2017 U.S. Department of Veterans Affairs/U.S. Department of
      Defense Clinical Practice Guideline: Management of Type 2 Diabetes Mellitus.
AB  - Description: In April 2017, the U.S. Department of Veterans Affairs (VA) and the
      U.S. Department of Defense (DoD) approved a joint clinical practice guideline for
      the management of type 2 diabetes mellitus. Methods: The VA/DoD Evidence-Based
      Practice Work Group convened a joint VA/DoD guideline development effort that
      included a multidisciplinary panel of practicing clinician stakeholders and
      conformed to the Institute of Medicine's tenets for trustworthy clinical practice
      guidelines. The guideline panel developed key questions in collaboration with the
      ECRI Institute, which systematically searched and evaluated the literature
      through June 2016, developed an algorithm, and rated recommendations by using the
      GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.
      Recommendations: This synopsis summarizes key features of the guideline in 7
      areas: patient-centered care and shared decision making, glycemic biomarkers,
      hemoglobin A1c target ranges, individualized treatment plans, outpatient
      pharmacologic treatment, glucose targets for critically ill patients, and
      treatment of hospitalized patients.

PMID- 29059688
TI  - When Clinical Practice Guidelines Collide: Finding a Way Forward.

PMID- 29059689
TI  - In-State and Interstate Associations Between Gun Shows and Firearm Deaths and
      Injuries: A Quasi-experimental Study.
AB  - Background: Gun shows are an important source of firearms, but no adequately
      powered studies have examined whether they are associated with increases in
      firearm injuries. Objective: To determine whether gun shows are associated with
      short-term increases in local firearm injuries and whether this association
      differs by the state in which the gun show is held. Design: Quasi-experimental.
      Setting: California. Participants: Persons in California within driving distance
      of gun shows. Measurements: Gun shows in California and Nevada between 2005 and
      2013 (n = 915 shows) and rates of firearm-related deaths, emergency department
      visits, and inpatient hospitalizations in California. Results: Compared with the
      2 weeks before, postshow firearm injury rates remained stable in regions near
      California gun shows but increased from 0.67 injuries (95% CI, 0.55 to 0.80
      injuries) to 1.14 injuries (CI, 0.97 to 1.30 injuries) per 100 000 persons in
      regions near Nevada shows. After adjustment for seasonality and clustering,
      California shows were not associated with increases in local firearm injuries
      (rate ratio [RR], 0.99 [CI, 0.97 to 1.02]) but Nevada shows were associated with
      increased injuries in California (RR, 1.69 [CI, 1.16 to 2.45]). The pre-post
      difference was significantly higher for Nevada shows than California shows (ratio
      of RRs, 1.70 [CI, 1.17 to 2.47]). The Nevada association was driven by
      significant increases in firearm injuries from interpersonal violence (RR, 2.23
      [CI, 1.01 to 4.89]) but corresponded to a small increase in absolute numbers.
      Nonfirearm injuries served as a negative control and were not associated with
      California or Nevada gun shows. Results were robust to sensitivity analyses.
      Limitation: Firearm injuries were examined only in California, and gun show
      occurrence was not randomized. Conclusion: Gun shows in Nevada, but not
      California, were associated with local, short-term increases in firearm injuries
      in California. Differing associations for California versus Nevada gun shows may
      be due to California's stricter firearm regulations. Primary Funding Source:
      National Institutes of Health; University of California, Berkeley; and Heising
      Simons Foundation.

PMID- 29059690
TI  - Introducing a Patient Portal and Electronic Tablets to Inpatient Care.

PMID- 29059691
TI  - Identifying Trends in Undiagnosed Diabetes in U.S. Adults by Using a Confirmatory
      Definition: A Cross-sectional Study.
AB  - Background: A common belief is that one quarter to one third of all diabetes
      cases remain undiagnosed. However, such prevalence estimates may be overstated by
      epidemiologic studies that do not use confirmatory testing, as recommended by
      clinical diagnostic criteria. Objective: To provide national estimates of
      undiagnosed diabetes by using a confirmatory testing strategy, in line with
      clinical practice guidelines. Design: Cross-sectional study. Setting: National
      Health and Nutrition Examination Survey results from 1988 to 1994 and 1999 to
      2014. Participants: U.S. adults aged 20 years and older. Measurements: Confirmed
      undiagnosed diabetes was defined as elevated levels of fasting glucose (>=7.0
      mmol/L [>=126 mg/dL]) and hemoglobin A1c (>=6.5%) in persons without diagnosed
      diabetes. Results: The prevalence of total (diagnosed plus confirmed undiagnosed)
      diabetes increased from 5.5% (9.7 million adults) in 1988 to 1994 to 10.8% (25.5
      million adults) in 2011 to 2014. Confirmed undiagnosed diabetes increased during
      the past 2 decades (from 0.89% in 1988 to 1994 to 1.2% in 2011 to 2014) but has
      decreased over time as a proportion of total diabetes cases. In 1988 to 1994, the
      percentage of total diabetes cases that were undiagnosed was 16.3%; by 2011 to
      2014, this estimate had decreased to 10.9%. Undiagnosed diabetes was more common
      in overweight or obese adults, older adults, racial/ethnic minorities (including
      Asian Americans), and persons lacking health insurance or access to health care.
      Limitation: Cross-sectional design. Conclusion: Establishing the burden of
      undiagnosed diabetes is critical to monitoring public health efforts related to
      screening and diagnosis. When a confirmatory definition is used, undiagnosed
      diabetes is a relatively small fraction of the total diabetes population; most
      U.S. adults with diabetes (about 90%) have received a diagnosis of the condition.
      Primary Funding Source: National Institutes of Health, National Institute of
      Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood
      Institute.

PMID- 29059692
TI  - Technology and Medicine: Reimagining Provider Visits as the New Tertiary Care.

PMID- 29059693
TI  - [Ethics Consultation on the ICU: The Clinically Oriented Method of Counselling].
AB  - When ethical conflicts arise on the ICU, an ethics case consultation is useful.
      The aim of this consult is a qualified reflection of the moral values,
      convictions and assumptions involved in the case. The "clinically oriented method
      of counselling" provides an adequate structure for case consultations on the ICU.
      The moral assumptions and estimations contained in medical indications,
      prognosis, therapeutic aims, risk-benefit assessment and issues of quality of
      life are discussed and a consensus is sought for. This method is familiar to
      hospital staff and will effectively support mutual understanding and agreement
      among physicians, nursing staff and family members. A consensus, facilitated by
      ethics consultation, expresses the shared belief, that the therapeutic options in
      question are both scientifically sound and humane. On the one hand the consensus
      assures the appropriateness of therapeutic goals and therapeutic means, on the
      other hand it proves the assessment, that patient wishes and preferences have
      been considered as conclusive as possible.

PMID- 29059694
TI  - [Reduction of post-surgical pain by Manual Medicine following tonsillectomy in
      adults].
AB  - Objective Postoperative pain after tonsillectomy (TE) can usually be treated
      sufficiently by non-steroidal anti-inflammatory drugs (NSAIDs). In some patients,
      however, postoperative pain is more prominent on one side of the neck. Our
      clinical experience has demonstrated that these patients often show a segmental
      hypomobility of the upper cervical joints that can be successfully treated by
      manual medicine (MM). The analgetic effectiveness of this treatment was
      investigated in a prospective, randomized, placebocontrolled, single-blind study.
      Material and Methods 52 adults with exceptionally strong (visual analog scale VAS
      > 4) and/or unilateral pain after TE (between day 1 and 4) were included in this
      study. Postoperatively (TE) pain scores were immediately evaluated by VAS before
      (t0) and after (t1) the treatment (MM) as well as 4 hours (t2) and 1 day later
      (t3). Results Results show a significantly higher reduction in pain in the verum
      group compared to the placebo group (t1: p = 0.012, t3: p = 0.012, both
      Bonferroni-adjusted). The difference to t2 was not significant (p = 0.54
      Conclusion This study has demonstrated effective pain reduction by manual
      medicine in adults with exceptionally strong and/or unilateral pain after TE and
      cervical hypomobolity.

PMID- 29059695
TI  - [Auditory Processing Disorder: Is The Diagnosis Already Possible In First
      Graders?]
AB  - OBJECTIVE: Significant differences in performance on an eclectic German test
      battery for Auditory Processing Disorders (APD) was found in the most diagnostic
      tools between children with APD and controls in the 2nd, 3rd and 4th school year
      of primary education. Aim of the present study was to examine whether it is also
      the case for first graders. MATERIAL AND METHODS: The performance in the
      behavioral test battery (including 14 specific auditory tests) was compared in
      two subject groups (aged 6-8 yrs): 41 first graders with APD of a clinical
      database, 37 typically developing first graders without APD (controls). RESULTS:
      Significant mean group differences were detected in the performance on 12 of 14
      tests, because children with APD showed lower scores (excepted from two PaTsy
      subtests: sound frequencies; sound intensities). The significance concerning the
      monaural threshold values narrowly retained statistical significance with
      Bonferroni correction. The controls mastered the PaTsy-subtests only in 86-89 %
      of all cases, children with APD in 73-83 %. The test scores of both boys and
      girls with APD were lower than those of their peers without APD. CONCLUSIONS:
      First graders with versus without APD could be significantly distinguished.
      Generally, there was seen a trend that in first graders the same performance was
      reduced as in elementary school pupils of higher grade level. For use in clinical
      diagnosis of APD, nonverbal auditory tests for the investigated specific age
      segment appears debatable.

PMID- 29059696
TI  - Social Morbidity in Relation to Bowel Functional Outcomes and Quality of Life in
      Anorectal Malformations and Hirschsprung's Disease.
AB  - BACKGROUND:  Anorectal malformations (ARMs) and Hirschsprung's disease (HD) are
      chronic bowel conditions associated with varying degrees of fecal incontinence.
      We aimed to discuss the contemporary status of social morbidity associated with
      ARMs and HD in the long term after contemporary treatments. MATERIALS AND
      METHODS:  The bowel functional outcomes of our recent institutional series up to
      adulthood were reviewed and compared for ARMs and HD. The Rintala score was used
      to evaluate bowel function, which includes an assessment of the social effects of
      the condition. In this study, the social outcomes in our population of patients
      with ARMs and HD were specifically analyzed in relation to the surveyed
      functional outcomes, our previously collected data on quality of life (QoL) and
      the current literature. RESULTS:  Mild ARMs were associated with a minimal risk
      of social morbidity consistent with good outcomes. In severe ARMs and HD, social
      problems were reported steadily among all age groups studied. Impairment of
      domains of fecal control were present among 53 to 89% of patients with social
      problems, including frequent symptoms (>1/week) in up to 39%. Involuntary gas
      leakage contributed to social morbidity in 15 to 27%. Comparison with QoL data
      suggested that social morbidity experienced during childhood may continue to
      affect emotional domains of QoL in later life, despite improvements in bowel
      function by adulthood. CONCLUSION:  Patients with severe ARMs and HD are at risk
      of social restrictions from impairment of bowel function despite contemporary
      surgical treatments. However, the QoL outcomes in adulthood may be more
      influenced by self-perceptions of illness formed from childhood than disease
      specific factors. Strategies to reduce the psychological morbidity associated
      with these conditions that includes parental involvement from the outset may
      improve outcomes.

PMID- 29059697
TI  - Stimulation of the mesencephalic locomotor region for gait recovery after stroke.
AB  - OBJECTIVE: One-third of all stroke survivors are unable to walk, even after
      intensive physiotherapy. Thus, other concepts to restore walking are needed.
      Because electrical stimulation of the mesencephalic locomotor region (MLR) is
      known to elicit gait movements, this area might be a promising target for
      restorative neurostimulation in stroke patients with gait disability. The present
      study aims to delineate the effect of high-frequency stimulation of the MLR (MLR
      HFS) on gait impairment in a rodent stroke model. METHODS: Male Wistar rats
      underwent photothrombotic stroke of the right sensorimotor cortex and chronic
      implantation of a stimulating electrode into the right MLR. Gait was assessed
      using clinical scoring of the beam-walking test and video-kinematic analysis
      (CatWalk) at baseline and on days 3 and 4 after experimental stroke with and
      without MLR-HFS. RESULTS: Kinematic analysis revealed significant changes in
      several dynamic and static gait parameters resulting in overall reduced gait
      velocity. All rats exhibited major coordination deficits during the beam-walking
      challenge and were unable to cross the beam. Simultaneous to the onset of MLR
      HFS, a significantly higher walking speed and improvements in several dynamic
      gait parameters were detected by the CatWalk system. Rats regained the ability to
      cross the beam unassisted, showing a reduced number of paw slips and misses.
      INTERPRETATION: MLR-HFS can improve disordered locomotor function in a rodent
      stroke model. It may act by shielding brainstem and spinal locomotor centers from
      abnormal cortical input after stroke, thus allowing for compensatory and
      independent action of these circuits. Ann Neurol 2017;82:828-840.

PMID- 29059698
TI  - Communicating Geographical Risks in Crisis Management: The Need for Research.
AB  - In any crisis, there is a great deal of uncertainty, often geographical
      uncertainty or, more precisely, spatiotemporal uncertainty. Examples include the
      spread of contamination from an industrial accident, drifting volcanic ash, and
      the path of a hurricane. Estimating spatiotemporal probabilities is usually a
      difficult task, but that is not our primary concern. Rather, we ask how analysts
      can communicate spatiotemporal uncertainty to those handling the crisis. We
      comment on the somewhat limited literature on the representation of spatial
      uncertainty on maps. We note that many cognitive issues arise and that the
      potential for confusion is high. We note that in the early stages of handling a
      crisis, the uncertainties involved may be deep, i.e., difficult or impossible to
      quantify in the time available. In such circumstance, we suggest the idea of
      presenting multiple scenarios.

PMID- 29059699
TI  - Identification of the genomic region under epigenetic regulation during non
      alcoholic fatty liver disease progression.
AB  - AIM: The progression of non-alcoholic fatty liver disease (NAFLD) is affected by
      epigenetics. We undertook co-methylation and differentially methylated region
      (DMR) analyses to identify the genomic region that is under epigenetic regulation
      during NAFLD progression. METHODS: We collected liver biopsy specimens from 60
      Japanese patients with NAFLD and classified these into mild (fibrosis stages 0-2)
      or advanced (fibrosis stages 3-4) NAFLD. We carried out a genome-wide DNA
      methylation analysis and identified the differentially methylated CpGs between
      mild and advanced NAFLD. Differentially methylated regions with multiple
      consecutive differentially methylated CpGs between mild and advanced NAFLD were
      extracted. RESULTS: Co-methylation analysis showed that individual differentially
      methylated CpG sites were clustered into three modules. The CpG sites clustered
      in one module were hypomethylated in advanced NAFLD and their annotated genes
      were enriched for "immune system" function. The CpG sites in another module were
      hypermethylated and their annotated genes were enriched for "mitochondria" or
      "lipid particle", and "lipid metabolism" or "oxidoreductase activity".
      Hypomethylated DMRs included tumorigenesis-related genes (FGFR2, PTGFRN, and
      ZBTB38), the expressions of which are upregulated in advanced NAFLD. Tumor
      suppressor MGMT had two DMRs and was downregulated. Conversely, FBLIM1 and CYR61,
      encoding proteins that reduce cell proliferation, showed hypomethylated DMRs and
      were upregulated. Expression of the antioxidant gene NQO1 was upregulated, with a
      hypomethylated DMR. The DMR containing cancer-related MIR21 was hypomethylated in
      advanced NAFLD. CONCLUSIONS: Co-methylation and DMR analyses suggest that the
      NAFLD liver undergoes mitochondrial dysfunction, decreased lipid metabolism, and
      impaired oxidoreductase activity, and acquires tumorigenic potential at the
      epigenetic level.

PMID- 29059700
TI  - Favorable response to immunosuppressive combination therapy with mizoribine and
      azathioprine in children with primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC), with no curative intervention, can progress
      to end-stage liver disease. Mizoribine, a purine antimetabolite, has never been
      used for the management of PSC. To evaluate the role of mizoribine with
      azathioprine we undertook a preliminary clinical study in children with PSC.
      Children with PSC and autoimmune features were simultaneously treated with
      mizoribine and azathioprine. Ursodeoxycholic acid or mesalazine were not
      regulated. The primary end-points of our study included improvement of aspartate
      aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase. Liver
      histology, immunostaining studies of the liver, and magnetic resonance
      cholangiopancreatography (MRCP) were also assessed. We have treated four PSC
      children: two treatment-naive patients (cases 1 and 2), and two with established
      liver cirrhosis (cases 3 and 4). Both case 1 and 2 showed a normalization of
      liver enzymes and case 2 showed an improvement in MRCP findings. Cases 3 and 4
      also showed an improvement in varices, MRCP findings, and liver histology. The
      combination therapy may be effective for some children with PSC and autoimmune
      features. By ameliorating both parenchymal inflammation and cholangiopathy of
      PSC, the therapy might improve the prognosis for patients. It awaits further
      prospective studies to confirm the efficacy of this therapy in patients with PSC.

PMID- 29059702
TI  - Perceptions of Risk and Vulnerability Following Exposure to a Major Natural
      Disaster: The Calgary Flood of 2013.
AB  - Many studies have examined the general public's flood risk perceptions in the
      aftermath of local and regional flooding. However, relatively few studies have
      focused on large-scale events that affect tens of thousands of people within an
      urban center. Similarly, in spite of previous research on flood risks, unresolved
      questions persist regarding the variables that might influence perceptions of
      risk and vulnerability, along with management preferences. In light of the
      opportunities presented by these knowledge gaps, the research reported here
      examined public perceptions of flood risk and vulnerability, and management
      preferences, within the city of Calgary in the aftermath of extensive flooding in
      2013. Our findings, which come from an online survey of residents, reveal that
      direct experience with flooding is not a differentiating factor for risk
      perceptions when comparing evacuees with nonevacuees who might all experience
      future risks. However, we do find that judgments about vulnerability-as a
      function of how people perceive physical distance-do differ according to one's
      evacuation experience. Our results also indicate that concern about climate
      change is an important predictor of flood risk perceptions, as is trust in
      government risk managers. In terms of mitigation preferences, our results reveal
      differences in support for large infrastructure projects based on whether
      respondents feel they might actually benefit from them.

PMID- 29059701
TI  - Interferon regulatory factor 1-Rab27a regulated extracellular vesicles promote
      liver ischemia/reperfusion injury.
AB  - : The role and regulators of extracellular vesicle (EV) secretion in hepatic
      ischemia/reperfusion (IR) injury have not been defined. Rab27a is a guanosine
      triphosphatase known to control EV release. Interferon regulatory factor 1 (IRF
      1) is a transcription factor that plays an important role in liver IR and
      regulates certain guanosine triphosphatases. However, the relationships among IRF
      1, Rab27a, and EV secretion are largely unknown. Here, we show induction of IRF-1
      and Rab27a both in vitro in hypoxic hepatocytes and in vivo in warm IR and
      orthotopic liver transplantation livers. Interferon gamma stimulation, IRF-1
      transduction, or IR promoted Rab27a expression and EV secretion. Meanwhile,
      silencing of IRF-1 decreased Rab27a expression and EV secretion. Rab27a silencing
      decreased EV secretion and liver IR injury. Ten putative IRF-1 binding motifs in
      the 1,692-bp Rab27a promoter region were identified. Chromatin
      immunoprecipitation and electrophoretic mobility shift assay verified five
      functional IRF-1 binding motifs, which were confirmed by a Rab27a promoter
      luciferase assay. IR-induced EVs contained higher oxidized phospholipids (OxPL).
      OxPLs on the EV surface activated neutrophils through the toll-like receptor 4
      pathway. OxPL-neutralizing E06 antibody blocked the effect of EVs and decreased
      liver IR injury. CONCLUSION: These findings provide a novel mechanism by which
      IRF-1 regulates Rab27a transcription and EV secretion, leading to OxPL activation
      of neutrophils and subsequent hepatic IR injury. (Hepatology 2018;67:1056-1070).

PMID- 29059703
TI  - Cutaneous metastasis as the first presentation of hepatocellular carcinoma.

PMID- 29059704
TI  - Toward Probabilistic Prediction of Flash Flood Human Impacts.
AB  - This article focuses on conceptual and methodological developments allowing the
      integration of physical and social dynamics leading to model forecasts of
      circumstance-specific human losses during a flash flood. To reach this objective,
      a random forest classifier is applied to assess the likelihood of fatality
      occurrence for a given circumstance as a function of representative indicators.
      Here, vehicle-related circumstance is chosen as the literature indicates that
      most fatalities from flash flooding fall in this category. A database of flash
      flood events, with and without human losses from 2001 to 2011 in the United
      States, is supplemented with other variables describing the storm event, the
      spatial distribution of the sensitive characteristics of the exposed population,
      and built environment at the county level. The catastrophic flash floods of May
      2015 in the states of Texas and Oklahoma are used as a case study to map the
      dynamics of the estimated probabilistic human risk on a daily scale. The results
      indicate the importance of time- and space-dependent human vulnerability and risk
      assessment for short-fuse flood events. The need for more systematic human impact
      data collection is also highlighted to advance impact-based predictive models for
      flash flood casualties using machine-learning approaches in the future.

PMID- 29059683
TI  - Association analysis identifies 65 new breast cancer risk loci.
AB  - Breast cancer risk is influenced by rare coding variants in susceptibility genes,
      such as BRCA1, and many common, mostly non-coding variants. However, much of the
      genetic contribution to breast cancer risk remains unknown. Here we report the
      results of a genome-wide association study of breast cancer in 122,977 cases and
      105,974 controls of European ancestry and 14,068 cases and 13,104 controls of
      East Asian ancestry. We identified 65 new loci that are associated with overall
      breast cancer risk at P < 5 * 10-8. The majority of credible risk single
      nucleotide polymorphisms in these loci fall in distal regulatory elements, and by
      integrating in silico data to predict target genes in breast cells at each locus,
      we demonstrate a strong overlap between candidate target genes and somatic driver
      genes in breast tumours. We also find that heritability of breast cancer due to
      all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched
      relative to the genome-wide average, with strong enrichment for particular
      transcription factor binding sites. These results provide further insight into
      genetic susceptibility to breast cancer and will improve the use of genetic risk
      scores for individualized screening and prevention.

PMID- 29059705
TI  - Low synovial double negative T and gammadelta T cells predict longer free-disease
      survival in oligoarticular JIA.
AB  - BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oJIA) is the most
      frequent form of chronic arthritis in children; the clinical course is extremely
      variable. In this study we have characterized by flow cytometry synovial B and T
      cells subsets in patients with oJIA in order to identify any parameters that
      could predict a more aggressive course of disease. METHODS: B and T cells from
      synovial fluid (SF) of 39 patients with oJIA were characterized by flow
      cytometry. In 22 patients SF was analysed at the onset of the disease (GroupA),
      in 17 SF was analysed at articular relapse (Group B). All patients in Group A
      were followed up for at least for 2 years after SF analysis: 13 patients relapsed
      during the follow-up period. RESULTS: Comparison of SF from Group A and Group B
      demonstrated an activated phenotype in relapsed patients, with higher Switched
      Memory B cells (58.53 vs 36.07% of CD19+, P-value 0.004) and lower Naive B cells
      (8.53 vs 25.9 of CD19+, P-value 0.002) in Group B. Furthermore, patients from
      Group A who did not relapse showed lower percentages of synovial DNT (2.38 vs
      1.50% of CD3 + TCRalpha/beta+, P-value 0.025) and gammadelta T cells (19.1 vs
      15.0% of CD3+ cells, P-value 0.004) at the onset, if compared with other Group A
      patients. CONCLUSIONS: In oJIA relapse SF present an activated B phenotype.
      Patients at disease onset with DNTs <1.8% and/or gammadelta T cells <16% of CD3+
      in synovial fluid have longer free-disease survival. (c) 2017 International
      Clinical Cytometry Society.

PMID- 29059707
TI  - Judicial Murder-Suicides in Van Diemen's Land.
AB  - On the morning of December 17, 1827, nine convicts were executed by public
      hanging in Hobart Town, the capital of the British colony of Van Diemen's Land
      (now the Australian state of Tasmania). Two months previously they had drowned
      senior Constable George Rex on Small Island, which was part of the penal
      settlement at Macquarie Harbor, in front of five bound and gagged witnesses. They
      offered no defence at their trial. Examination of the Tasmanian colonial convict
      records shows that "suicide by lottery" involved convicts choosing two men, one
      to die and the other to kill him. The witnesses would earn a respite when taken
      away for the trial, and the murderer would be executed. "Death by gallows" could
      be considered a nineteenth-century version of an orchestrated suicide reminiscent
      of more modern "death by cop." This category of "judicial" murder-suicide expands
      the range of contemporary classifications of dyadic deaths.

PMID- 29059706
TI  - Pacinian Corpuscles in the Human Fetal Finger and Thumb: A Study Using 3D
      Reconstruction and Immunohistochemistry.
AB  - The detailed distribution of Pacinian corpuscles was evaluated by viewing the
      transverse sections of all fingers and thumbs, including the interdigital areas,
      from eight hands of five fetuses of gestational age 28-33 weeks (crown-rump
      length 230-290 mm). Among the 40 fingers and thumbs, serial sections were
      prepared for 3D reconstructions of nerve elements in the distal and middle
      phalangeal segments of three fifth fingers; in these three fingers, the distal
      segment contained 45-75 Pacinian corpuscles. These Pacinian corpuscles were 0.2
      1.0 mm in length and 0.05-0.3 mm in thickness, oriented along the proximodistal
      axis and arranged along the palmar digital nerve branches. Other than beneath the
      digital skin, small corpuscles (<0.1 mm in thickness) were observed within the
      tendon sheath of the flexors in the middle or distal segment of five fetuses and
      in the nail beds of four fetuses. Clusters of 5-20 corpuscles formed bouquet- or
      tree-like arrangements along neurovascular bundles in the fingers, thumbs and
      interdigital areas. Because the space beneath the skin was thick and loose in the
      interdigital area, trees in the interdigital area were up to 2 mm long.
      Regardless of site, the central core of each corpuscle was positive for S100
      protein, while the core and parts of the capillaries in the corpuscle were weakly
      positive for nestin. Because corpuscles in the tendon sheath and nail bed, as
      well as bouquet- and tree-like arrangements of corpuscles, have not been reported
      in adults, these morphologies are likely specific to fetuses. Anat Rec, 2017. (c)
      2017 Wiley Periodicals, Inc. Anat Rec, 301:154-165, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29059708
TI  - Self-restraint spillover: Inhibitory control disrupts appetite regulation among
      ruminators.
AB  - OBJECTIVE: People can use inhibitory control to temporarily inhibit their
      personal preferences to achieve their long-term goals. According to the ego
      fixation model (Koole et al., 2014), ruminators have difficulties relaxing
      inhibitory control, leading them to continue inhibiting their personal needs,
      even when this is no longer required by the situation. Inhibitory control may
      thus disrupt healthy appetite regulation among ruminators. METHOD: Among 324
      Dutch undergraduate students (218 women; Mage  = 21.5), different inhibitory
      control states were manipulated by varying whether or not participants exerted
      inhibitory control (Study 1) or priming high versus low inhibitory control (Study
      2). All participants then performed a food-tasting task. Healthy appetite
      regulation was defined as a positive correlation between level of food
      deprivation and preference for high-calorie foods. RESULTS: For taste ratings,
      the interaction between inhibitory control and rumination was significant in each
      study: Inhibitory control disrupted healthy appetite regulation in taste
      preferences among ruminators, but not among non-ruminators. For eating behavior,
      the same interaction effect was significant when the two studies were combined.
      CONCLUSIONS: Inhibitory control disrupts healthy appetite regulation among
      ruminators. These findings suggest the need for caution in interventions that
      rely on inhibitory control, especially among samples with compulsive thought
      tendencies.

PMID- 29059710
TI  - Correlation of Noncancer Benchmark Doses in Short- and Long-Term Rodent
      Bioassays.
AB  - This study investigated whether, in the absence of chronic noncancer toxicity
      data, short-term noncancer toxicity data can be used to predict chronic toxicity
      effect levels by focusing on the dose-response relationship instead of a critical
      effect. Data from National Toxicology Program (NTP) technical reports have been
      extracted and modeled using the Environmental Protection Agency's Benchmark Dose
      Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits
      (BMDLs) have been modeled for all NTP pathologist identified significant
      nonneoplastic lesions, final mean body weight, and mean organ weight of 41
      chemicals tested by NTP between 2000 and 2012. Models were then developed at the
      chemical level using orthogonal regression techniques to predict chronic (two
      years) noncancer health effect levels using the results of the short-term (three
      months) toxicity data. The findings indicate that short-term animal studies may
      reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can
      allow for faster development of human health toxicity values for risk assessment
      for chemicals that lack chronic toxicity data.

PMID- 29059711
TI  - Author's response to Letter to the Editor.

PMID- 29059709
TI  - Microglial dysfunction as a key pathological change in adrenomyeloneuropathy.
AB  - OBJECTIVE: Mutations in ABCD1 cause the neurodegenerative disease,
      adrenoleukodystrophy, which manifests as the spinal cord axonopathy
      adrenomyeloneuropathy (AMN) in nearly all males surviving into adulthood.
      Microglial dysfunction has long been implicated in pathogenesis of brain disease,
      but its role in the spinal cord is unclear. METHODS: We assessed spinal cord
      microglia in humans and mice with AMN and investigated the role of ABCD1 in
      microglial activity toward neuronal phagocytosis in cell culture. Because
      mutations in ABCD1 lead to incorporation of very-long-chain fatty acids into
      phospholipids, we separately examined the effects of lysophosphatidylcholine
      (LPC) upon microglia. RESULTS: Within the spinal cord of humans and mice with
      AMN, upregulation of several phagocytosis-related markers, such as MFGE8 and
      TREM2, precedes complement activation and synapse loss. Unexpectedly, this occurs
      in the absence of overt inflammation. LPC C26:0 added to ABCD1-deficient
      microglia in culture further enhances MFGE8 expression, aggravates phagocytosis,
      and leads to neuronal injury. Furthermore, exposure to a MFGE8-blocking antibody
      reduces phagocytic activity. INTERPRETATION: Spinal cord microglia lacking ABCD1
      are primed for phagocytosis, affecting neurons within an altered metabolic
      milieu. Blocking phagocytosis or specific phagocytic receptors may alleviate
      synapse loss and axonal degeneration. Ann Neurol 2017;82:813-827.

PMID- 29059713
TI  - Lone Actor Terrorist Attack Planning and Preparation: A Data-Driven Analysis.
AB  - This article provides an in-depth assessment of lone actor terrorists' attack
      planning and preparation. A codebook of 198 variables related to different
      aspects of pre-attack behavior is applied to a sample of 55 lone actor
      terrorists. Data were drawn from open-source materials and complemented where
      possible with primary sources. Most lone actors are not highly lethal or
      surreptitious attackers. They are generally poor at maintaining operational
      security, leak their motivations and capabilities in numerous ways, and generally
      do so months and even years before an attack. Moreover, the "loneness" thought to
      define this type of terrorism is generally absent; most lone actors uphold social
      ties that are crucial to their adoption and maintenance of the motivation and
      capability to commit terrorist violence. The results offer concrete input for
      those working to detect and prevent this form of terrorism and argue for a re
      evaluation of the "lone actor" concept.

PMID- 29059714
TI  - Using a Web-Based Diary Method to Estimate Risks and Benefits from Fish
      Consumption.
AB  - Accurate estimates of the amount and type of fish people eat are necessary to
      determine the health benefits and risks of consuming fish, and to assess
      compliance with fish consumption guidelines issued for fish affected by chemical
      contaminants. We developed a web-based and mobile-phone-enabled diary methodology
      to collect detailed fish consumption information for two 16-week periods in the
      summers of 2014 and 2015. We recruited study participants from two populations
      living in the Great Lakes region-women of childbearing age (WCBA) and urban
      residents who had purchased fishing licenses. In this article, we describe the
      methodology in detail and provide evidence related to participation rates, the
      representativeness of our sample over time, and both convergent validity and
      reliability of the data collection methods. Overall, 56% of WCBA and 50% of urban
      anglers provided complete data across both data collection periods. Among those
      who provided information at the beginning of Year 2, 97% of both audiences
      provided information throughout the entire 16-week period. Those who participated
      throughout the two-year period were slightly older on average (1.9-2.5 years)
      than other members of our original samples. We conclude that using diaries with
      web and smartphone technology, combined with incentives and persistent
      communication, has strong potential for assessing fish consumption in other areas
      of the country or for situations where the potential risks associated with fish
      consumption are substantial and the cost can be justified.

PMID- 29059712
TI  - Selectivity, cell permeability and oral availability studies of novel bromophenol
      derivative HPN as protein tyrosine phosphatase 1B inhibitor.
AB  - BACKGROUND AND PURPOSE: Protein tyrosine phosphatase 1B (PTP1B) negatively
      regulates insulin signalling by tyrosine dephosphorylation of the insulin
      receptor. It is a highly validated target for type 2 diabetes therapeutics. Here,
      the anti-diabetic effects of HPN were evaluated in the diabetic BKS db mice.
      EXPERIMENTAL APPROACH: The mode of inhibition of PTP1B by HPN was determined
      according to the Lineweaver-Burk plot. A surface plasmon resonance assay and
      molecular docking were used to study the interaction between HPN and PTP1B. C2C12
      skeletal muscle cells were used to investigate the cell permeability of HPN and
      the effect of HPN on insulin signalling pathways. Long-term effects of HPN on
      glycaemic control were investigated in diabetic BKS db mice. Glycogen contents in
      liver and muscle were determined. Furthermore, changes in the number of beta
      cells were evaluated by Gomori staining. KEY RESULTS: HPN was identified as a
      specific PTP1B inhibitor. HPN directly interacted with PTP1B by binding to the
      catalytic domain through hydrogen bonds in a competitive mode. Approximately
      56.98% of HPN entered into the cultured C2C12 myotubes. HPN ameliorated the
      impaired insulin signalling in palmitate-treated C2C12 myocytes. Notably, oral
      administration of HPN significantly protected mice from hyperglycaemia,
      dyslipidemia and hyperinsulinaemia. HPN also enhanced the storage of glycogen in
      liver and muscle. Moreover, HPN obviously improved the beta cell numbers of the
      pancreatic islets. CONCLUSION AND IMPLICATIONS: Our results indicate that HPN is
      a specific PTP1B inhibitor, with anti-diabetic properties and good cell
      permeability and oral availability.

PMID- 29059715
TI  - Suicide by Medication Overdose in Prison: A Study of Three Cases.
AB  - Suicide is one of the principal causes of mortality in a prison environment.
      Although suicide by medication overdose is less frequent than suicide by hanging,
      self-strangulation, or vein cutting, it raises questions as to how the
      medications are obtained, particularly in view of the specific organization of
      the medication circuit in prisons. We present three cases of suicide by
      medication overdose involving different therapeutic classes with different
      distribution circuits and review the regulatory requirements and the measures
      that could be taken to prevent such suicides.

PMID- 29059716
TI  - Morphological Characterization of the Myenteric Plexus of the Ileum and Distal
      colon of Dogs Affected by Muscular Dystrophy.
AB  - Duchenne-like muscular dystrophy (canine dystrophinopathy) is a hereditary
      degenerative disease characterized by muscle changes similar to those described
      for Duchenne muscular dystrophy (DMD) and by alterations in the smooth muscles of
      the gastrointestinal tract. Some authors have suggested that these abnormalities
      may be associated with intestinal motility. This study analyzed the nitrergic and
      cholinergic neurons and P2X7 receptor expression in the myenteric plexus of the
      ileum and distal colon of dogs with muscular dystrophy. Immunohistochemical
      techniques were used to detect nitric oxide synthase (NOS) and acetylcholine
      transferase (ChAT) expression and to label all HuC/D- and P2X7 receptor
      immunoreactive (IR) neurons. Transmission electron microscopy and basic histology
      were performed for further analysis. The results showed that nitrergic neurons
      exhibited a Dogiel type I morphology in the ileum and distal colon. The neuronal
      profile results showed that there were fewer NOS-, ChAT-, and HuC/D-IR neurons in
      the ileum than in the distal colon in the dystrophic (DT) dogs. Additionally,
      there were more NOS-, ChAT- and HuC/D-IR neurons per ganglion in the distal colon
      than in the ileum. The P2X7 receptor-expressing neurons colocalized with
      nitrergic and cholinergic neurons. Transmission and light microscopy revealed
      collagen between the muscle fibers, between the circular and longitudinal muscle
      layers and within the myenteric ganglia of dogs with muscular dystrophy. These
      findings provide a morphological description of the myenteric neurons in the
      ileum and distal colon of these DT dogs and may contribute to a better
      understanding of the gastrointestinal disorders found in patients with DMD. Anat
      Rec, 301:673-685, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29059717
TI  - Weapon Use in Korean Homicide: Differences Between Homicides Involving Sharp and
      Blunt Instruments.
AB  - On the basis of information regarding 276 homicides committed in South Korea
      between 1987 and 2008, we compared offenders' and victims' characteristics,
      injury locations, weapon-related behavior, and offending behavior between
      homicides involving sharp and blunt instruments. The victims of sharp-force
      homicide were much younger relative to those of blunt-force homicide. In
      addition, homicides involving blunt instruments were more likely to be committed
      by offenders who lived with the victims. Most sharp-force homicides involved
      injuries to the torso, while blunt-force homicides involved mainly head injuries.
      Furthermore, perpetrators of sharp-force homicides tended to preselect their
      weapons, while those of blunt-force homicides were likely to use weapons of
      opportunity. Logistic regression analysis identified a number of factors,
      including injury location and body transportation, which significantly predicted
      weapon type. As this was the first South Korean study to compare sharp- and blunt
      force homicides, the results have practical implications for homicide
      investigations.

PMID- 29059718
TI  - The First Record of Incidences of Ankylosis in Seven Triplefin Fishes (Pisces:
      Tripterygiidae) from New Zealand.
AB  - Different cases of vertebral ankylosis were examined in seven tripterygiid
      species obtained from waters around New Zealand. The skeletal deformities
      observed are located in the caudal region of the vertebral column. Those occurred
      in Forsterygion nigripenne, Matanui bathytaton and in one specimen of Ruanoho
      whero were severe cases. The mechanism of the formation of vertebral ankylosis
      and the causes behind such anomaly were discussed. Further studies are needed to
      relate specific pollutants with the observed types of deformities. Anat Rec,
      2017. (c) 2017 Wiley Periodicals, Inc. Anat Rec, 301:39-45, 2018. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29059719
TI  - Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer
      according to Tumorigenicity in Patient-Derived Xenograft Models.
AB  - Purpose: Although the use of xenograft models is increasing, few studies have
      compared the clinical features or outcomes of epithelial ovarian cancer (EOC)
      patients according to the tumorigenicity of engrafted specimens. The purpose of
      this study was to evaluate whether tumorigenicity was associated with the
      clinical features and outcomes of EOC patients. Materials and Methods: Eighty
      eight EOC patients who underwent primary or interval debulking surgery from June
      2014 to December 2015 were included. Fresh tumor specimens were implanted
      subcutaneously on each flank of immunodeficient mice. Patient characteristics,
      progression-free survival (PFS), and germline mutation spectra were compared
      according to tumorigenicity. Results: Xenografts were established successfully
      from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular
      invasion and there was a propensity to engraft successfully with high-grade
      tumors. Tumors from patientswho underwent non-optimal (residual disease >= 1 cm)
      primary orinterval debulking surgery had a significantly greater propensity to
      achieve tumorigenicity than those who received optimal surgery. In addition,
      patients whose tumors became engrafted seemed to have a shorter PFS and more
      frequent germline mutations than patients whose tumors failed to engraft.
      Tumorigenicity was a significant factor for predicting PFS with advanced
      International Federation of Gynecology and Obstetrics stage and high-grade
      cancers. Conclusions: Tumorigenicity in a xenograft model was a strong prognostic
      factor and was associated with more aggressive tumors in EOC patients. Xenograft
      models can be useful as a preclinical tool to predict prognosis and could be
      applied to further pharmacologic and genomic studies on personalized treatments.

PMID- 29059720
TI  - Sugarcane bagasse as exclusive roughage for dairy cows in smallholder livestock
      system.
AB  - OBJECTIVE: The study aimed to evaluate sugarcane bagasse as roughage in lactating
      cow on feed intake, digestibility, ingestive behavior, milk production and
      composition, and microbial protein synthesis. METHODS: Ten Girolando cows at
      initial body weight of 450+/-25.6 kg and at 143.7+/-30.7 days in milk were
      assigned in two 5*5 Latin square designs. Five 21-day experimental periods were
      adopted (1 degrees  to 14-day: diets adaptation period; 15 degrees  to 21-day:
      data collection and sampling period). The diets consisted of four different
      levels of sugarcane bagasse (45%, 50%, 55%, and 60%) and a control diet, commonly
      adopted in the region, based on spineless cactus (25% sugarcane bagasse),
      formulated to meet 12 kg/d milk yield. RESULTS: The dry matter (DM), organic
      matter (OM), and total digestible nutrients intakes and DM and OM digestibilities
      observed for 45% and 50% bagasse inclusion were similar to control diet, while
      that 55% and 60% bagasse inclusion were lower. Cows fed control diet, and bagasse
      diets of 45%, and 50% levels had the nutritional requirements attended, that
      guaranteed 12 kg/d of milk yield. The crude protein intake and digestibility of
      cows fed 45%, 50%, and 55% of bagasse inclusion were similar to control diet. The
      neutral detergent fiber (NDF) intake and digestibility differ for all bagasse
      diets related to control diet, while the non-fiber carbohydrates intake and
      digestibility for cows fed 45% of bagasse were similar for control diet. The
      intakes and digestibilities of nutrients decreased linearly in function of
      bagasse inclusion; NDF and indigestible NDF intakes did not vary. The ruminating
      time, feeding and rumination efficiency, microbial protein synthesis and milk
      yield decreased linearly with sugarcane bagasse inclusion. CONCLUSION: Sugarcane
      bagasse decreases milk production; however, its inclusion level in between 45% to
      50% associated to concentrate could replace diets based on spineless cactus for
      crossbred dairy cow's producing 12 kg/d of milk.

PMID- 29059721
TI  - Short-term grazing behavior of cattle under indoor housing for a new-bred
      tetraploid ruzigrass (Brachiaria ruziziensis Germain et Everard).
AB  - OBJECTIVE: The preference evaluation of cattle is an important factor for
      estimation and improvement of the grazing amounts of newly introduced or bred
      grasses or cultivars in barn. This study was performed to assess the grazing
      behavior (the amount of grazing and/or the grazing speed) of cattle as indirect
      method using newly bred Brachiaria ruziziensis tetraploid strain 'OKI-1'(BR) hay
      as treatment group and Cloris gayana 'Callide' (CG) hay as control group. It also
      compared the feasibility of using behavioral differences between two groups as
      one criteria for evaluating preference by Japanese black cattle in barn. METHODS:
      Three experiments were carried out using 12 growing Japanese Black cattle
      including 6 males and 6 females. In each experiment, the four Japanese Black
      cattle (2 males and 2 females) were placed in separated stall and allowed to
      graze BR and CG in manger that was separated into two portions for about 30 min.
      The position and behavior of the cattle were recorded, and weighed the residual
      of each gay at 15 and 30 minutes after experiment start. RESULTS: The BR was
      superior to CG in chemical composition such as protein, fibers and non-fibrous
      carbohydrate. The cattle, over all, tended to prefer BR over CG in the first half
      15 minutes in terms of the time spent and amount of grazing. Additionally,
      growing cattle exhibited neophilia for BR bred newly. CONCLUSION: These findings
      indicated the current approach could be applied for one of criteria to evaluate
      the preference of hay by Japanese black cattle under indoor housing environment.

PMID- 29059722
TI  - Genome-wide association study reveals genetic loci and candidate genes for
      average daily gain in Duroc pigs.
AB  - OBJECTIVE: Average daily gain (ADG) is an important target trait of pig breeding
      programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic
      regions that are associated with ADG in the Duroc pig population. METHODS: We
      performed a genome-wide association study involving 390 Duroc boars and by using
      the PorcineSNP60K Beadchip and two linear models. RESULTS: After quality control,
      we detected 3,5971 SNPs, which included seven SNPs that are significantly
      associated with the ADG of pigs. We identified six quantitative trait loci (QTL)
      regions for ADG. These QTLs included four previously reported QTLs on Sus scrofa
      chromosome (SSC) 1, SSC5, SSC9, and SSC13, as well as two novel QTLs on SSC6 and
      SSC16. In addition, we selected six candidate genes (general transcription factor
      3C polypeptide 5, high mobility group AT-hook 2, nicotinamide
      phosphoribosyltransferase, oligodendrocyte transcription factor 1, pleckstrin
      homology and RhoGEF domain containing G4B, and ENSSSCG00000031548) associated
      with ADG on the basis of their physiological roles and positional information.
      These candidate genes are involved in skeletal muscle cell differentiation, diet
      induced obesity, and nervous system development. CONCLUSION: This study
      contributes to the identification of the casual mutation that underlies QTLs
      associated with ADG and to future pig breeding programs based on marker-assisted
      selection. Further studies are needed to elucidate the role of the identified
      candidate genes in the physiological processes involved in ADG regulation.

PMID- 29059723
TI  - Whole-genome association and genome partitioning revealed variants and explained
      heritability for total number of teats in a Yorkshire pig population.
AB  - OBJECTIVE: The study was designed to perform a genome-wide association (GWA) and
      partitioning of genome using Illumina's PorcineSNP60 Beadchip in order to
      identify variants and determine the explained heritability for the total number
      of teats in Yorkshire pig. METHODS: After screening with the following criteria:
      minor allele frequency, MAF<=0.01; Hardy-Weinberg equilibrium, HWE<=0.000001, a
      pair-wise genomic relationship matrix was produced using 42,953 single nucleotide
      polymorphisms (SNPs). A genome-wide mixed linear model-based association analysis
      (MLMA) was conducted. And for estimating the explained heritability with genome-
      or chromosome-wide SNPs the genetic relatedness estimation through maximum
      likelihood approach was used in our study. RESULTS: The MLMA analysis and false
      discovery rate p-values identified three significant SNPs on two different
      chromosomes (rs81476910 and rs81405825 on SSC8; rs81332615 on SSC13) for total
      number of teats. Besides, we estimated that 30% of variance could be explained by
      all of the common SNPs on the autosomal chromosomes for the trait. The maximum
      amount of heritability obtained by partitioning the genome were 0.22+/-0.05,
      0.16+/-0.05, 0.10+/-0.03 and 0.08+/-0.03 on SSC7, SSC13, SSC1, and SSC8,
      respectively. Of them, SSC7 explained the amount of estimated heritability along
      with a SNP (rs80805264) identified by genome-wide association studies at the
      empirical p value significance level of 2.35E-05 in our study. Interestingly,
      rs80805264 was found in a nearby quantitative trait loci (QTL) on SSC7 for the
      teat number trait as identified in a recent study. Moreover, all other
      significant SNPs were found within and/or close to some QTLs related to ovary
      weight, total number of born alive and age at puberty in pigs. CONCLUSION: The
      SNPs we identified unquestionably represent some of the important QTL regions as
      well as genes of interest in the genome for various physiological functions
      responsible for reproduction in pigs.

PMID- 29059724
TI  - Effects of harvest time and added molasses on nutritional content, ensiling
      characteristics and in vitro degradation of whole crop wheat.
AB  - OBJECTIVE: Wheat is an alternative to corn silage for ruminant feeding in
      northern China. This study examined the effects of harvest time and added
      molasses on nutritional content, ensiling characteristics and in vitro
      degradation of whole crop wheat (WCW). METHODS: Fresh WCW at the milk-ripe stage
      was harvested at 0700 h (i.e., in the morning [Mo]) and 1700 h (i.e., in the
      afternoon [Af]), and then immediately used to prepare silage and make hay.
      Commercial molasses was added to Af WCW at 0%, 2%, 4%, and 6% (fresh weight)
      proportions. The WCW treated with molasses was mixed thoroughly prior to
      ensiling. RESULTS: Dry matter (DM), neutral detergent fiber, water soluble
      carbohydrate (WSC) content (p<0.01), accumulative gas production in 72 h (GP72h,
      77.46 mL/g vs 95.15 mL/g) and dry matter disappearance in vitro (69.15% vs
      76.77%) were lower (p<0.05), while crude protein (CP) content was higher for WCW
      silage (WCWS) compared to WCW (p<0.01). The propionic acid and butyric acid
      concentrations in WCWS from Mo WCW were 1.47% and 0.26%, respectively. However,
      the propionic and butyric acid concentrations were negligible, while the ammonia
      nitrogen/total nitrogen (NH3-N/TN, p<0.01) concentration was lower and the rate
      of gas production at 50% of the maximum (17.05 mL/h vs 13.94 mL/h, p<0.05) was
      higher for Af WCWS compared to Mo WCWS. The incubation fluid's NH3-N
      concentration was lower in WCWS and Af WCW compared to Mo WCW (p<0.05). The CP
      and WSC content increased with increasing molasses levels (p<0.05). Furthermore,
      the pH (p<0.01) and time when gas production was 50% of the maximum (2.78 h vs
      3.05 h, p<0.05) were lower in silage treated with 4% molasses than silage without
      molasses. CONCLUSION: Harvesting wheat crops in the afternoon and adding molasses
      at 4% level to WCW optimally improved ensiling characteristics, leading to well
      preserved silage.

PMID- 29059726
TI  - Porcine growth hormone induces the nuclear localization of porcine growth hormone
      receptor in vivo.
AB  - OBJECTIVE: Recent studies have challenged the traditional paradigm that growth
      hormone receptor (GHR) displays physiological functions only in the cell
      membrane. It has been demonstrated that GHR localizes to the cell nucleus and
      still exhibits important physiological roles. The phenomenon of nuclear
      localization of growth hormone (GH)-induced GHR has previously been described in
      vitro. However, until recently, whether GH could induce nuclear localization of
      GHR in vivo was unclear. METHODS: In the present study, we used pig as an animal
      model, and porcine growth hormone (pGH) or saline was injected into the inferior
      vena cava. We subsequently observed the localization of porcine growth hormone
      receptor (pGHR) using multiple techniques, including, immunoprecipitation and
      Western-blotting, indirect immunofluorescence assay and electronmicroscopy.
      RESULTS: The results showed that pGH could induce nuclear localization of pGHR.
      Taken together, the results of the present study provided the first demonstration
      that pGHR was translocated to cell nuclei under pGH stimulation in vivo.
      CONCLUSION: Nuclear localization of pGHR induced by the in vivo pGH treatment
      suggests new functions and/or novel roles of nuclear pGHR, which deserve further
      study.

PMID- 29059725
TI  - Bio-protective potential of lactic acid bacteria: Effect of Lactobacillus sakei
      and Lactobacillus curvatus on changes of the microbial community in vacuum
      packaged chilled beef.
AB  - OBJECTIVE: This study was to determine the bacterial diversity and monitor the
      community dynamic changes during storage of vacuum-packaged sliced raw beef as
      affected by Lactobacillus sakei and Lactobacillus curvatus. METHODS: L. sakei and
      L. curvatus were separately incubated in vacuumed-packaged raw beef as bio
      protective cultures to inhibit the naturally contaminating microbial load.
      Dynamic changes of the microbial diversity of inoculated or non-inoculated
      (control) samples were monitored at 4 degrees C for 0 to 38 days, using
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE).
      RESULTS: The DGGE profiles of DNA directly extracted from non-inoculated control
      samples highlighted the order of appearance of spoilage bacteria during storage,
      showing that Enterbacteriaceae and Pseudomonas fragi emerged early, then
      Brochothrix thermosphacta shared the dominant position, and finally, Pseudomonas
      putida showed up became predominant. Compared with control, the inoculation of
      either L. sakei or L. curvatus significantly lowered the complexity of microbial
      diversity and inhibited the growth of spoilage bacteria (p<0.05). Interestingly,
      we also found that the dominant position of L. curvatus was replaced by
      indigenous L. sakei after 13 d for L. curvatus-inoculated samples. Plate counts
      on selective agars further showed that inoculation with L. sakei or L. curvatus
      obviously reduced the viable counts of Enterbacteraceae, Pseudomonas spp. and B.
      thermosphacta during later storage (p< 0.05), with L. sakei exerting greater
      inhibitory effect. Inoculation with both bio-protective cultures also
      significantly decreased the total volatile basic nitrogen values of stored
      samples (p<0.05). CONCLUSION: Taken together, the results proved the benefits of
      inoculation with lactic acid bacteria especially L. sakei as a potential way to
      inhibit growth of spoilage-related bacteria and improve the shelf life of vacuum
      packaged raw beef.

PMID- 29059728
TI  - Re: Open Suprapubic versus Retropubic Prostatectomy in the Treatment of Benign
      Prostatic Hyperplasia during Resident's Learning Curve: A Randomized Controlled
      Trial.

PMID- 29059729
TI  - Re: Effect of Transurethral Split of the Prostate Using a Double-Columnar Balloon
      Catheter for Benign Prostatic Hyperplasia: A Single-Center Experience of 565
      Consecutive Patients.

PMID- 29059727
TI  - Hemicastration induced spermatogenesis-related DNA methylation and gene
      expression changes in mice testis.
AB  - OBJECTIVE: Hemicastration is a unilateral orchiectomy to remove an injured
      testis, which can induce hormonal changes and compensatory hypertrophy of the
      remaining testis, and may influence spermatogenesis. However, the underlying
      molecular mechanisms are poorly understood. Here, we investigated the impact of
      hemicastration on remaining testicular function. METHODS: Prepubertal mice (age
      24 days) were hemicastrated, and their growth was monitored until they reached
      physical maturity (age 72 days). Subsequently, we determined testis DNA
      methylation patterns using reduced representation bisulfite sequencing of normal
      and hemicastrated mice. Moreover, we profiled the testicular gene expression
      patterns by RNA sequencing (RNA-seq) to examine whether methylation changes
      affected gene expression in hemicastrated mice. RESULTS: Hemicastration did not
      significantly affect growth or testosterone (p>0.05) compared with control. The
      genome-wide DNA methylation pattern of remaining testis suggested that
      substantial genes harbored differentially methylated regions (1,139) in gene
      bodies, which were enriched in process of protein binding and cell adhesion.
      Moreover, RNA-seq results indicated that 46 differentially expressed genes (DEGs)
      involved in meiotic cell cycle, synaptonemal complex assembly and spermatogenesis
      were upregulated in the hemicastration group, while 197 DEGs were downregulated,
      which were related to arachidonic acid metabolism. Integrative analysis revealed
      that proteasome 26S subunit ATPase 3 interacting protein gene, which encodes a
      protein crucial for homologous recombination in spermatocytes, exhibited promoter
      hypomethylation and higher expression level in hemicastrated mice. CONCLUSION:
      Global profiling of DNA methylation and gene expression demonstrated that
      hemicastration-induced compensatory response maintained normal growth and
      testicular morphological structure in mice.

PMID- 29059730
TI  - Re: Association of Suicidality and Depression with 5alpha-Reductase Inhibitors.

PMID- 29059731
TI  - Re: Prevalence of Proteinuria and Other Abnormalities in Urinalysis Performed in
      the Urology Clinic.

PMID- 29059732
TI  - Re: Identifying Prevalence and Risk Factors for Mild Cognitive Impairment in
      Adults Presenting for Urological Evaluation.

PMID- 29059733
TI  - Re: The Near-Future Impact of Retirement on the Urologic Workforce: Results from
      the American Urological Association Census.

PMID- 29059734
TI  - Re: Evaluation and Establishment of a Ward-Based Geriatric Liaison Service for
      Older Urological Surgical Patients: Proactive Care of Older People Undergoing
      Surgery (POPS)-Urology.

PMID- 29059735
TI  - Re: Psychological Stress in Geriatric Patients with Genito-Urinary Cancers.

PMID- 29059736
TI  - Re: Who Gets Testosterone? Patient Characteristics Associated with Testosterone
      Prescribing in the Veteran Affairs System: A Cross-Sectional Study.

PMID- 29059737
TI  - Re: Differentiating Renal Neoplasms from Simple Cysts on Contrast-Enhanced CT on
      the Basis of Attenuation and Homogeneity.

PMID- 29059738
TI  - Re: Management of Bacteriuria in Veterans Affairs Hospitals.

PMID- 29059740
TI  - Re: Has Sliding-Clip Renorrhaphy Eliminated the Need for Collecting System Repair
      during Robot-Assisted Partial Nephrectomy?

PMID- 29059739
TI  - Re: Etiology of Symptomatic Urethritis in Men and Association with Sexual
      Behaviors.

PMID- 29059741
TI  - Re: Male Sexual Function in New Zealand: A Population-Based Cross-Sectional
      Survey of the Prevalence of Erectile Dysfunction in Men Aged 40-70 Years.

PMID- 29059742
TI  - Re: Selective Arterial Clamping Does Not Improve Outcomes in Robot-Assisted
      Partial Nephrectomy: A Propensity-Score Analysis of Patients without Impaired
      Renal Function.

PMID- 29059743
TI  - Re: Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients
      with Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham
      Controlled Trial.

PMID- 29059744
TI  - Re: A Retrospective Analysis of Risk Factors for IPP Reservoir Entry into the
      Peritoneum after Abdominal Wall Placement.

PMID- 29059745
TI  - Re: Neurovascular Bundle Size Measured on 3.0-T Magnetic Resonance Imaging is
      Associated with the Recovery of Erectile Function after Robot-Assisted Radical
      Prostatectomy.

PMID- 29059746
TI  - Re: Relationship between Sexual Position and Severity of Penile Fracture.

PMID- 29059747
TI  - Re: Microsurgical Identification and Excision of an Intratesticular Mass.

PMID- 29059748
TI  - Re: Vasectomy Reversal Semen Analysis: New Reference Ranges Predict Pregnancy.

PMID- 29059750
TI  - Re: Posttranslational Modifications in Spermatozoa and Effects on Male Fertility
      and Sperm Viability.

PMID- 29059749
TI  - Re: Sperm Aneuploidy after Testicular Cancer Treatment: Data from a Prospective
      Multicenter Study Performed within the French Centre d'Etude et de Conservation
      des Oeufs et du Sperme Network.

PMID- 29059751
TI  - Re: Regulation of the Sperm Calcium Channel CatSper by Endogenous Steroids and
      Plant Triterpenoids.

PMID- 29059752
TI  - Re: Changes in Cajal Cell Density in Ureteropelvic Junction Obstruction in
      Children.

PMID- 29059753
TI  - Re: Evidence for a Delay in Diagnosis of Wilms' Tumour in the UK Compared with
      Germany: Implications for Primary Care for Children.

PMID- 29059754
TI  - Re: Differences between Intrinsic and Extrinsic Ureteropelvic Junction
      Obstruction Related to Crossing Vessels: Histology and Functional Analyses.

PMID- 29059755
TI  - Re: Use of Muscle Pedicle Flaps for Failed Bladder Neck Closure in the Exstrophy
      Spectrum.

PMID- 29059756
TI  - Re: Use of Human Acellular Dermal Matrix during Classic Bladder Exstrophy Repair.

PMID- 29059757
TI  - Re: Remote Ischemic Conditioning on Recipients of Deceased Renal Transplants Does
      Not Improve Early Graft Function: A Multicenter Randomized, Controlled Clinical
      Trial.

PMID- 29059758
TI  - Re: Big Data, Predictive Analytics, and Quality Improvement in Kidney
      Transplantation: A Proof of Concept.

PMID- 29059759
TI  - Re: Public Perceptions of Overlapping Surgery.

PMID- 29059760
TI  - Re: Types and Distribution of Payments from Industry to Physicians in 2015.

PMID- 29059761
TI  - Re: Changes in Hospital Quality Associated with Hospital Value-Based Purchasing.

PMID- 29059762
TI  - Re: Small Intestinal Submucosa Grafting for Peyronie Disease: Outcomes and
      Patient Satisfaction.

PMID- 29059763
TI  - Re: Anterior Urethroplasty Has Transitioned to an Outpatient Procedure without
      Serious Rise in Complications: Data from the National Surgical Quality
      Improvement Program.

PMID- 29059764
TI  - Re: Safety and Surgical Outcomes of Same-Day Anterior Urethroplasty.

PMID- 29059766
TI  - Re: Oxalobacter formigenes Colonization Normalizes Oxalate Excretion in a Gastric
      Bypass Model of Hyperoxaluria.

PMID- 29059765
TI  - Re: Effects of Juice Processing on Oxalate Contents in Carambola Juice Products.

PMID- 29059767
TI  - Re: A Survey of Patient Preferences Regarding Medical Expulsive Therapy following
      the SUSPEND Trial.

PMID- 29059768
TI  - Re: alpha-Lipoic Acid Treatment Prevents Cystine Urolithiasis in a Mouse Model of
      Cystinuria.

PMID- 29059769
TI  - Re: Urinary Collecting System Invasion is Associated with Poor Survival in
      Patients with Clear-Cell Renal Cell Carcinoma.

PMID- 29059770
TI  - Re: Clear Cell Type A and B Molecular Subtypes in Metastatic Clear Cell Renal
      Cell Carcinoma: Tumor Heterogeneity and Aggressiveness.

PMID- 29059771
TI  - Re: Anti-Inflammatory Use May Not Negatively Impact Oncologic Outcomes following
      Intravesical BCG for High-Grade Non-Muscle-Invasive Bladder Cancer.

PMID- 29059772
TI  - Re: Refraining from Smoking for 15 Years or More Reduced the Risk of Tumor
      Recurrence in Non-Muscle Invasive Bladder Cancer Patients.

PMID- 29059773
TI  - Re: Clinical and Therapeutic Factors Associated with Adverse Pathological
      Outcomes in Clinically Node-Negative Patients Treated with Neoadjuvant Cisplatin
      Based Chemotherapy and Radical Cystectomy.

PMID- 29059774
TI  - Re: Treatment Decision Regret among Long-Term Survivors of Localized Prostate
      Cancer: Results from the Prostate Cancer Outcomes Study.

PMID- 29059775
TI  - Re: Prognostic Utility of Biopsy-Derived Cell Cycle Progression Score in Patients
      with National Comprehensive Cancer Network Low-Risk Prostate Cancer Undergoing
      Radical Prostatectomy: Implications for Treatment Guidance.

PMID- 29059776
TI  - Re: Effective Combinatorial Immunotherapy for Castration-Resistant Prostate
      Cancer.

PMID- 29059777
TI  - Re: Weight Change, Obesity and Risk of Prostate Cancer Progression among Men with
      Clinically Localized Prostate Cancer.

PMID- 29059778
TI  - Re: Second Malignant Neoplasms and Cause of Death in Patients with Germ Cell
      Cancer: A Danish Nationwide Cohort Study.

PMID- 29059779
TI  - Re: Profiling of Long Non-Coding RNAs Identifies LINC00958 and LINC01296 as
      Candidate Oncogenes in Bladder Cancer.

PMID- 29059780
TI  - Re: Loss of Tumor Suppressor KDM6A Amplifies PRC2-Regulated Transcriptional
      Repression in Bladder Cancer and Can be Targeted through Inhibition of EZH2.

PMID- 29059781
TI  - Re: ARF Confers a Context-Dependent Response to Chemotherapy in Muscle-Invasive
      Bladder Cancer.

PMID- 29059782
TI  - Re: Cost Profiles and Budget Impact of Rechargeable versus Non-Rechargeable
      Sacral Neuromodulation Devices in the Treatment of Overactive Bladder Syndrome.

PMID- 29059783
TI  - Re: Effect of Continuous Positive Airway Pressure on Nocturnal Urine Production
      in Patients with Obstructive Sleep Apnea Syndrome.

PMID- 29059784
TI  - Re: Urinary Neurotrophic Peptides in Postmenopausal Women with and without
      Overactive Bladder.

PMID- 29059785
TI  - Re: Association between Joint Hypermobility and Pelvic Organ Prolapse in Women: A
      Systematic Review and Meta-Analysis.

PMID- 29059786
TI  - Re: Evaluation of the Urinary Microbiota of Women with Uncomplicated Stress
      Urinary Incontinence.

PMID- 29059787
TI  - Letter to the Editor Regarding "The Extended Lateral Supraorbital Approach and
      Extradural Anterior Clinoidectomy Through a Frontopterio-Orbital Window:
      Technical Note and Pilot Surgical Series".

PMID- 29059788
TI  - Letter to the Editor Regarding "Extent of T1+C Intensity Is a Predictor of Blood
      Loss in Resection of Meningioma".

PMID- 29059789
TI  - Letter to the Editor Regarding "Burr-Hole Drainage for Chronic Subdural Hematoma
      under Low-Dose Acetylsalicylic Acid: a Comparative Risk Analysis Study".

PMID- 29059790
TI  - Meningocele and Meningoencephalocele of the Lateral Wall of Sphenoidal Sinus.

PMID- 29059791
TI  - Imaging Classification and Treatment of Spontaneous Intracranial Fusiform and
      Dissecting Aneurysms.

PMID- 29059792
TI  - In Reply to the Letter to the Editor "Imaging Classification and Treatment of
      Spontaneous Intracranial Fusiform and Dissecting Aneurysms".

PMID- 29059794
TI  - Workshops and tutorials.
AB  - Provides an abstract for each of the tutorial and workshop presentations and a
      list of presenters. The complete presentations were not made available for
      publication as part of the conference proceedings.

PMID- 29059795
TI  - Wearable health monitoring using capacitive voltage-mode Human Body
      Communication.
AB  - Rapid miniaturization and cost reduction of computing, along with the
      availability of wearable and implantable physiological sensors have led to the
      growth of human Body Area Network (BAN) formed by a network of such sensors and
      computing devices. One promising application of such a network is wearable health
      monitoring where the collected data from the sensors would be transmitted and
      analyzed to assess the health of a person. Typically, the devices in a BAN are
      connected through wireless (WBAN), which suffers from energy inefficiency due to
      the high-energy consumption of wireless transmission. Human Body Communication
      (HBC) uses the relatively low loss human body as the communication medium to
      connect these devices, promising order(s) of magnitude better energy-efficiency
      and built-in security compared to WBAN. In this paper, we demonstrate a health
      monitoring device and system built using Commercial-Off-The-Shelf (COTS) sensors
      and components, that can collect data from physiological sensors and transmit it
      through a) intra-body HBC to another device (hub) worn on the body or b) upload
      health data through HBC-based human-machine interaction to an HBC capable
      machine. The system design constraints and signal transfer characteristics for
      the implemented HBC-based wearable health monitoring system are measured and
      analyzed, showing reliable connectivity with >8* power savings compared to
      Bluetooth low-energy (BTLE).

PMID- 29059796
TI  - Keynote & Plenary Speakers.
AB  - Lists the Keynote or Plenary speakers and provides an abstract of the
      presentations with a brief professional biography of each presenter. The complete
      presentations were not made available for publication as part of the conference
      proceedings.

PMID- 29059797
TI  - A self-powered glucose biosensor based on pyrolloquinoline quinone glucose
      dehydrogenase and bilirubin oxidase operating under physiological conditions.
AB  - A novel biosensing system capable of simultaneously sensing glucose and powering
      portable electronic devices such as a digital glucometer is described. The
      biosensing system consists of enzymatic glucose biofuel cell bioelectrodes
      functionalized with pyrolloquinoline quinone glucose dehydrogenase (PQQ-GDH) and
      bilirubin oxidase (BOD) at the bioanode and biocathode, respectively. A dual
      stage power amplification circuit is integrated with the single biofuel cell to
      amplify the electrical power generated. In addition, a capacitor circuit was
      incorporated to serve as the transducer for sensing glucose. The open circuit
      voltage of the optimized biofuel cell reached 0.55 V, and the maximum power
      density achieved was 0.23 mW/ cm2 at 0.29 V. The biofuel cell exhibited a
      sensitivity of 0.312 mW/mM.cm2 with a linear dynamic range of 3 mM - 20 mM
      glucose. The overall self-powered glucose biosensor is capable of selectively
      screening against common interfering species, such as ascorbate and urate and
      exhibited an operational stability of over 53 days, while maintaining 90 % of its
      activity. These results demonstrate the system's potential to replace the current
      glucose monitoring devices that rely on external power supply, such as a battery.

PMID- 29059798
TI  - Detection of needle to nerve contact based on electric bioimpedance and machine
      learning methods.
AB  - In an ongoing project for electrical impedance-based needle guidance we have
      previously showed in an animal model that intraneural needle positions can be
      detected with bioimpedance measurement. To enhance the power of this method we in
      this study have investigated whether an early detection of the needle only
      touching the nerve also is feasible. Measurement of complex impedance during
      needle to nerve contact was compared with needle positions in surrounding tissues
      in a volunteer study on 32 subjects. Classification analysis using Support-Vector
      Machines demonstrated that discrimination is possible, but that the sensitivity
      and specificity for the nerve touch algorithm not is at the same level of
      performance as for intra-neuralintraneural detection.

PMID- 29059799
TI  - Testing the need for carbon in salt/adhesive electrodes for surface
      electromyography measurements: Preliminary results.
AB  - We compared previously carbon/salt/adhesive (CSA) electrodes with Ag/AgCl
      electrodes for surface electromyography (sEMG) signals collection. We found no
      differences in amplitude, but CSA electrodes exhibited a significantly better
      response to noise and motion artifacts. However, the carbon component may not be
      needed, and the salt/adhesive (SA) mixture might be as good as CSA for such a
      task. Either CSA or SA mixtures have the potential to provide the unique
      advantages of having longer (theoretically infinite) shelf life and potentially
      lower cost, compared to the gold standard Ag/AgCl hydrogel electrodes. In order
      to determine if carbon contribution is necessary for effective sEMG measuring
      capabilities the mixture, the functionality of SA electrodes utilizing different
      levels of salt concentration were compared to the capabilities of CSA electrodes.
      The levels consisted of 10%, 15%, and 25% salt concentration. Six subjects have
      been recruited so far to collect simultaneous recordings of sEMG signals using
      CSA and SA electrodes, side-by-side on triceps brachii, tibial anterior muscles,
      biceps brachii and quadriceps femoris. For all three levels of salt concentration
      in the SA electrodes, high correlation was found to the CSA electrodes on the
      estimated linear envelopes, RMS envelope and power spectrum density. Furthermore,
      no significant differences in amplitude, compared to CSA electrodes, were found
      for the three concentrations. Based on signal-to-noise and signal-to-motion
      measures on the preliminary data set, it seems like adding carbon to the mixture
      improves the response to motion, but impairs the noise corruption of the sEMG
      signals.

PMID- 29059800
TI  - A rapid quantitative determination method of Luteinizing hormone with gold
      immunochromatographic strip.
AB  - Measurement of Luteinizing hormone (LH) levels is of great importance in guidance
      for pregnancy, diagnosis of ovarian diseases and evaluation of clinical effect.
      Gold immunochromatographic strip(GICS) assay is a rapid, simple, low-costs, and
      on-site technology. Quantitative detection of GICS has advantage over the
      traditional qualitative or semi-quantitative strip assay. In this paper, we
      developed a novel quantitative detection method for GICS based on smart-phone.
      First, smart-phone was used to acquire GICS image. Then, we applied the canny
      edge detection operator to extract the reading window from GICS image, and the
      fuzzy c-means (FCM) clustering algorithm to locate the test and control lines in
      the reading window. In order to reduce environmental interference, luminance
      compensation based on color constancy algorithms was applied. Finally, the
      property of the developed quantitative method is demonstrated by the detection of
      LH sample and clinical serum sample. Experimental results revealed that this
      method could achieve a low detection limit of 1.0 mIU/mL in a linear range from
      1.0 to 125.0 mIU/mL. Furthermore, the proposed method could be used for the
      determination of clinical serum samples and its corresponding correlation
      coefficients were 0.964. Results showed that this novel method could be an
      effective tool for the rapid quantitative determination of LH.

PMID- 29059801
TI  - Integration of piezo-capacitive and piezo-electric nanoweb based pressure sensors
      for imaging of static and dynamic pressure distribution.
AB  - Recently, highly flexible and soft pressure distribution imaging sensor is in
      great demand for tactile sensing, gait analysis, ubiquitous life-care based on
      activity recognition, and therapeutics. In this study, we integrate the piezo
      capacitive and piezo-electric nanowebs with the conductive fabric sheets for
      detecting static and dynamic pressure distributions on a large sensing area.
      Electrical impedance tomography (EIT) and electric source imaging are applied for
      reconstructing pressure distribution images from measured current-voltage data on
      the boundary of the hybrid fabric sensor. We evaluated the piezo-capacitive
      nanoweb sensor, piezo-electric nanoweb sensor, and hybrid fabric sensor. The
      results show the feasibility of static and dynamic pressure distribution imaging
      from the boundary measurements of the fabric sensors.

PMID- 29059802
TI  - Problem Based Learning for engineering.
AB  - the role of Problem Based Learning (PBL) is relative clear in domains such as
      medicine but its efficacy in engineering is as yet less certain. To clarify the
      role of PBL in engineering, a 3 day workshop was conducted for senior Brazilian
      engineering academics where they were given the theory and then an immersive PBL
      experience. One major purpose for running this workshop was for them to identify
      suitable courses where PBL could be considered. During this workshop, they were
      split in teams and given a diverse range of problems. At the conclusion of the
      workshop, a quantifiable survey was conducted and the results show that PBL can
      deliver superior educational outcomes providing the student group is drawn from
      the top 5% of the year 12 students, and that significantly higher resources are
      made available. Thus, any proposed PBL program in engineering must be able to
      demonstrate that it can meet these requirements before it can move forward to
      implementation.

PMID- 29059803
TI  - A course in prosthetics for the developing world: Merging education, research,
      and industry to teach biomedical design for social impact.
AB  - Under the auspices of the MIT D-Lab, a team of graduate students has instructed a
      course since 2008 that centers around teaching low-cost prosthetic design for
      resource-constrained environments. Recently, the course has evolved into a fully
      immersive design experience that pairs student teams with real-life international
      stakeholders and industry partners. Following this structure, projects initiated
      as part of the course have been tested at field sites around the world,
      stimulated further research, advanced student careers, raised additional grant
      money, and generated peer-reviewed publications and intellectual property.

PMID- 29059804
TI  - The role of a creative "joint assignment" project in biomedical engineering
      bachelor degree education.
AB  - Biomedical Engineering (BME) bachelor education aims to train qualified engineers
      who devote themselves to addressing biological and medical problems by
      integrating the technological, medical and biological knowledge. Design thinking
      and teamwork with other disciplines are necessary for biomedical engineers. In
      the current biomedical engineering education system of Shanghai University (SHU),
      however, such design thinking and teamwork through a practical project is
      lacking. This paper describes a creative "joint assignment" project in Shanghai
      University, China, which has provided BME bachelor students a two-year practical
      experience to work with students from multidisciplinary departments including
      sociology, mechanics, computer sciences, business and art, etc. To test the
      feasibility of this project, a twenty-month pilot project has been carried out
      from May 2015 to December 2016. The results showed that this pilot project
      obviously enhanced competitive power of BME students in Shanghai University, both
      in the capabilities of design thinking and teamwork.

PMID- 29059805
TI  - Design and development of an intelligent nursing bed - a pilot project of "joint
      assignment".
AB  - The "joint assignment" is a creative bachelor education project for Biomedical
      Engineering (BME) in Shanghai University (SHU), China. The objective of this
      project is to improve students' capabilities in design thinking and teamwork
      through practices in the process of the design and development of complex medical
      product. As the first step, a pilot project "design and development of
      intelligent nursing bed" was set up in May 2015. This paper describes details of
      how project organization and management, various teaching methods and scientific
      evaluation approaches were achieved in this pilot project. For example, a method
      containing one main line and four branches is taken to manage the project and
      "prototyping model" was used as the main research approach. As a result a multi
      win situation was achieved. The results showed, firstly, 62 bachelor students
      including 16 BME students were well trained. They improved themselves in use of
      practical tools, communication skills and scientific writing; Secondly,
      commercial companies received a nice product design on intelligent nursing bed,
      and have been working on industrializing it; Thirdly, the university and
      associated schools obtained an excellent practical education experience to
      supplement traditional class education; Fourthly and most importantly,
      requirements from end-users will be met. The results also showed that the "joint
      assignment" task could become a significant component in BME bachelor education.

PMID- 29059806
TI  - A hybrid, low-cost tissue-like epidural needle insertion simulator.
AB  - Epidural and spinal anesthesia are mostly performed "blind" without any medical
      imaging. Currently, training of these procedures is performed on human specimens,
      virtual reality systems, manikins and mostly in clinical practice supervised by a
      professional. In this study a novel hybrid, low-cost patient simulator for the
      training of needle insertion into the epidural space was designed. The patient
      phantom provides a realistic force feedback comparable with biological tissue and
      enables sensing of the needle tip position during insertion. A display delivers
      the trainee a real-time feedback of the needle tip position.

PMID- 29059807
TI  - Novel synthetic vertebrae provide realistic haptics for pedicle screw placement.
AB  - During vertebral surgery, misplaced pedicle screws can harm vital neural and
      vascular structures. Haptic distinction between cortical and cancellous bone
      structures is therefore essential for correct screw placement. This tactile
      experience during pedicle screw placement can be obtained by training on human or
      animal specimens even if expensive or ethically questionable. In this study,
      novel synthetic vertebrae were evaluated within a hybrid simulator to provide
      realistic haptics for the training of spine surgeries. Synthetic vertebrae were
      custommade of calcium powder-based composites imitating both, cancellous and
      cortical bone. The mechanical properties of synthetic surrogates were validated
      for pedicle screw placement and cement augmentation and were compared with those
      obtained from human vertebrae and insertion torques were analyzed. In human
      vertebrae pedicle screw torque measurements resulted in mean torque slopes of
      82+/-33Nm/m. Calcium carbonate-based materials achieved lower torques than the
      human bone whereas calcium phosphate-based bone surrogates showed comparable
      results. A further differentiation of the calcium phosphate-based vertebrae
      revealed, that synthetic vertebrae with lower amounts of blowing agent, achieved
      suitable torques (83 +/- 28Nm/m) in comparison to the human reference (p = 0.39).
      Cement application and subsequent fluoroscopy images confirmed, that the
      cancellous core of the synthetic vertebrae enabled cement augmentation. In
      conclusion, our findings suggest, that the artificial bone samples mimic the
      properties of human bone during pedicle screw placement and cement augmentation
      and are therefore suitable as synthetic vertebrae in a hybrid surgical simulator.

PMID- 29059808
TI  - Characterizing dynamic balance during adaptive locomotor learning.
AB  - In recent years, adaptation to walking on a split-belt treadmill has been used as
      a common paradigm to explore how humans and other vertebrates adapt to walking in
      an asymmetric environment. When people walk on a split-belt treadmill, they
      initially walk with an asymmetry characterized by steps of unequal length, then
      gradually adopt a symmetric walking pattern characterized by steps of the same
      length. Although it has been proposed that the adoption of a symmetric walking
      pattern may result from a desired to maintain dynamic balance, this has yet to be
      investigated. Therefore, we used a model and experiment to explore how dynamic
      balance is influenced by spatiotemporal asymmetry during walking on a split-belt
      treadmill. The model was constructed based on a two-state exponential model which
      updates foot placement at each step based on the asymmetry from the previous. In
      the experiment, participants adapted to walking on a split-belt treadmill with
      the left belt moving at 1.5 m/s and the right belt moving at 0.5 m/s.
      Retroreflective markers were used to measure lower extremity kinematics and to
      compute spatiotemporal metrics such as step length, dynamic margins of stability,
      and time-to-contact. We found that people showed greater margins of stability on
      the fast belt than on the slow belt during adaptation. This was accomplished by
      adjusting the angle of the leading limb, which determined the placement of their
      feet relative to the body's center of mass. The results also showed greater times
      to contact on the slow belt than on the fast belt during adaptation and the
      difference between the fast and slow belt decayed during adaptation. These
      experimental results were consistent with the simulation using the computational
      model. Our results help to improve our understanding of the role of biomechanics
      in driving adaptive changes to coordination when walking in novel environments.

PMID- 29059809
TI  - Early prediction of future hand movements using sEMG data.
AB  - We study in this work the feasibility of early prediction of hand movement based
      on sEMG signals to overcome the time delay issue of the conventional
      classification. Opposed to the classification task, the objective of early
      prediction is to predict a hand movement that is going to occur in the future
      given the information up to the current time point. The ability of early
      prediction may allow a hand prosthesis control system to compensate for the time
      delay and, as a result, improve the usability. Experimental results on the
      Ninapro database show that we can predict up to 300 ms ahead in the future while
      the prediction accuracy remains very close to that of the standard
      classification, i.e. it is just marginally lower. Furthermore, historical data
      prior the current time window is shown to be very important to improve
      performance, not only for the prediction but also the classification task.

PMID- 29059810
TI  - Muscle contractions in cyclic movements: Optimization of CIMAP algorithm.
AB  - During cyclic movements, the number of muscle activations and their timing are
      different from cycle to cycle. In a previous study, the CIMAP algorithm was
      proposed for grouping cycles showing similar EMG activation intervals, using
      dendrogram clustering. Even if the algorithm demonstrated good performances on a
      healthy population, the intra-cluster variability decreased when applied to
      datasets from pathological subjects. In this work we propose an optimized version
      of the CIMAP, comparing the performances of 8 different combinations of
      parameters used for the dendrogram construction. The cut-off point is also
      modified. The new and the original version of the algorithm are compared, in
      terms of intra-cluster variability, considering a population of 60 subjects, both
      healthy and pathological. The results show that the new CIMAP allows for
      obtaining clusters with lower variability with respect to the original version of
      the algorithm (p <; 0.001).

PMID- 29059811
TI  - Simple space-domain features for low-resolution sEMG pattern recognition.
AB  - In recent years, low-cost, low-power myoelectric control systems such as the Myo
      armband from Thalmic Labs have become available and unlocked tremendous
      possibilities for myoelectric controlled applications. However, due to the
      embedded system constraints, such sEMG control devices typically samples sEMG
      signals at a lower frequency. It is in doubt whether existing sEMG feature
      extraction methods are still valid on such low-resolution sEMG data. In addition,
      the feature extraction algorithms implemented on embedded devices must have low
      computational complexity in order to meet the real-time requirement. This paper
      aims to investigate effective features for low-resolution EMG pattern
      recognition. In particular, a set of novel computational efficient space-domain
      (SD) features (referred to as simple SD (SSD) features) have been developed to
      exploit the spatial relationships of sEMG signals recorded from the sensor array
      on the Myo armband. The proposed SSD feature set was evaluated with a linear
      discriminant analysis (LDA)-based classifier on a 9-gesture dataset. The
      experimental results indicate that using the SSD features increased the
      classification accuracy by 5% compared to using Hudgins' time-domain features.

PMID- 29059812
TI  - Movement augmentation to evaluate human control of locomotor stability.
AB  - Controlling center of mass (COM) position and velocity within a dynamic base of
      support is essential for gait stability. This skill is often compromised
      following neurologic injury, creating a need to develop effective interventions
      to enhance gait stability. A movement augmentation paradigm applied to walking
      could potentially be used to improve control of COM dynamics. We have developed a
      cable robot system, the Agility Trainer, to apply continuous frontal-plane forces
      to the pelvis during treadmill walking. This cable robot system uses a set of
      series elastic actuators powered by linear motors to create bilateral forces.
      Here we use the Agility Trainer to create a negative viscosity force field
      proportional to the subject's lateral velocity. Two healthy young subjects
      performed two 10-minute walking trials, Baseline and Negative Viscosity. During
      the first minute of walking in the Negative Viscosity field, participants'
      lateral COM motion became less controlled when compared to the rhythmic
      sinusoidal motion observed during Baseline walking. By the 10th minute of walking
      in the Negative Viscosity field the participants had adapted their gait patterns,
      decreasing their variation in peak lateral COM speed each stride. These results
      demonstrate that it is feasible to use the Agility Trainer to apply a movement
      augmentation paradigm to human walking.

PMID- 29059813
TI  - Ankle intrinsic stiffness is modulated by postural sway.
AB  - Dynamic ankle stiffness, which defines the relationship between joint position
      and the torque acting about it, determines the joint resistance to external
      perturbations. The contribution of joint stiffness to stance control is usually
      assumed to be constant; however, the stiffness may be modulated due to the
      ongoing sway during stance. This paper describes the results of the direct
      estimation of ankle intrinsic stiffness and its modulation with background torque
      during stance. Three subjects stood on a standing apparatus, while subjected to
      pulse perturbations of ankle position. The angle of center of mass, and ankle
      torque and angle were measured and individual torque responses to each position
      perturbation were analyzed. Each response lasted 90 milliseconds, where the mean
      of the torque record in the first 25 milliseconds was considered as its
      background torque. Ensemble of the responses with similar background torques were
      used to estimate the joint intrinsic stiffness. The estimated parameters showed
      that elastic element of the ankle intrinsic stiffness varied significantly (by a
      factor of 3) with background torque, i.e. the higher the background torque, the
      higher the stiffness. Thus ankle stiffness is not constant but varies greatly
      with postural sway.

PMID- 29059814
TI  - Predicting the outcome for patients in a heart transplantation queue using deep
      learning.
AB  - Heart transplantations have made it possible to extend the median survival time
      to 12 years for patients with end-stage heart diseases. This operation is
      unfortunately limited by the availability of donor organs and patients have to
      wait on average about 200 days in a waiting list before being operated. This
      waiting time varies considerably across the patients. In this paper, we studied
      the outcome for patients entering a transplantation waiting list using deep
      learning techniques. We implemented a model in the form of two-layer neural
      networks and we predicted the outcome as still waiting, transplanted or dead in
      the waiting list, at three different time points: 180 days, 365 days, and 730
      days. As data source, we used the United Network for Organ Sharing (UNOS)
      registry, where we extracted adult patients (>17 years) from January 2000 to
      December 2011. We trained our model using the Keras framework, and we report F1
      macro scores of respectively 0.674, 0.680, and 0.680 compared to a baseline of
      0.271. We also applied a backward elimination procedure, using our neural
      network, to extract the 10 most significant parameters predicting the patient
      status for the three different time points.

PMID- 29059815
TI  - Staged Inference using Conditional Deep Learning for energy efficient real-time
      smart diagnosis.
AB  - Recent progress in biosensor technology and wearable devices has created a
      formidable opportunity for remote healthcare monitoring systems as well as real
      time diagnosis and disease prevention. The use of data mining techniques is
      indispensable for analysis of the large pool of data generated by the wearable
      devices. Deep learning is among the promising methods for analyzing such data for
      healthcare applications and disease diagnosis. However, the conventional deep
      neural networks are computationally intensive and it is impractical to use them
      in real-time diagnosis with low-powered on-body devices. We propose Staged
      Inference using Conditional Deep Learning (SICDL), as an energy efficient
      approach for creating healthcare monitoring systems. For smart diagnostics, we
      observe that all diagnoses are not equally challenging. The proposed approach
      thus decomposes the diagnoses into preliminary analysis (such as healthy vs
      unhealthy) and detailed analysis (such as identifying the specific type of cardio
      disease). The preliminary diagnosis is conducted real-time with a low complexity
      neural network realized on the resource-constrained on-body device. The detailed
      diagnosis requires a larger network that is implemented remotely in cloud and is
      conditionally activated only for detailed diagnosis (unhealthy individuals). We
      evaluated the proposed approach using available physiological sensor data from
      Physionet databases, and achieved 38% energy reduction in comparison to the
      conventional deep learning approach.

PMID- 29059816
TI  - Classifying osteosarcoma patients using machine learning approaches.
AB  - Metabolomic data analysis presents a unique opportunity to advance our
      understanding of osteosarcoma, a common bone malignancy for which genomic and
      proteomic studies have enjoyed limited success. One of the major goals of
      metabolomic studies is to classify osteosarcoma in early stages, which is
      required for metastasectomy treatment. In this paper we subject our metabolomic
      data on osteosarcoma patients collected by the SJTU team to three classification
      methods: logistic regression, support vector machine (SVM) and random forest
      (RF). The performances are evaluated and compared using receiver operating
      characteristic curves. All three classifiers are successful in distinguishing
      between healthy control and tumor cases, with random forest outperforming the
      other two for cross-validation in training set (accuracy rate for logistic
      regression, support vector machine and random forest are 88%, 90% and 97%
      respectively). Random forest achieved overall accuracy rate of 95% with 0.99 AUC
      on testing set.

PMID- 29059817
TI  - Development of a three dimensional, multiscale agent-based model of ductal
      carcinoma in situ.
AB  - Ductal carcinoma in situ (DCIS) is the most commonly diagnosed form of non
      invasive breast cancer, constituting 20% of all new breast cancer cases in the
      United States. Although non-invasive, DCIS is usually treated surgically through
      resection. Interestingly, long-term survival studies have shown that patient
      survival rates are not significantly impacted by the type or resection,
      indicating that increased breast conservation through minimized surgical
      resection may indeed be possible. This requires a greater understanding of
      disease development, so that clinicians may more accurately determine surgical
      margins which minimize patient impact while maintaining survival rates. To this
      end, we have developed a three-dimensional, lattice-free multiscale agent based
      model of DCIS designed to help quantify ductal invasion rates, in order to allow
      clinicians to better estimate disease age and extent of invasion, and to predict
      surgical margins based on parameters obtainable from non-invasive testing (i.e.,
      mammography). Here, we present the model development to date, and discuss some
      preliminary results.

PMID- 29059818
TI  - Elucidating the biophysical processes responsible for the chromatic attributes of
      peripheral cyanosis.
AB  - The purple or blue coloration of hands and feet, known as peripheral cyanosis,
      can represent one of the initial signs of potentially life threatening medical
      conditions. Consequently, procedures aimed at its early detection and
      interpretation can help health-care professionals to select the appropriate
      treatment for these conditions. The effectiveness of such procedures, in turn,
      depends on the correct assessment of the biophysical processes responsible for
      eliciting this abnormal skin appearance. However, despite the diverse body of
      existing clinical research involving cyanosis, the interplay between
      physiological changes and the optical phenomena leading to cyanotic responses
      remains not fully understood. In this paper, we methodically examine this
      interplay through controlled in silico experiments. Among other relevant aspects,
      the results of our experiments demonstrate that Rayleigh scattering, a light
      attenuation phenomenon overlooked by previous studies on peripheral cyanosis,
      plays a pivotal role in the manifestation of cyanotic chromatic attributes. We
      believe that the insights derived from our experiments can contribute to the
      development of more effective protocols for the screening of medical conditions
      associated with peripheral cyanosis etiology.

PMID- 29059819
TI  - SMARTool: A tool for clinical decision support for the management of patients
      with coronary artery disease based on modeling of atherosclerotic plaque process.
AB  - SMARTool aims to the development of a clinical decision support system (CDSS) for
      the management and stratification of patients with coronary artery disease (CAD).
      This will be achieved by performing computational modeling of the main processes
      of atherosclerotic plaque growth. More specifically, computed tomography coronary
      angiography (CTCA) is acquired and 3-dimensional (3D) reconstruction is performed
      for the arterial trees. Then, blood flow and plaque growth modeling is employed
      simulating the major processes of atherosclerosis, such as the estimation of
      endothelial shear stress (ESS), the lipids transportation, low density
      lipoprotein (LDL) oxidation, macrophages migration and plaque development. The
      plaque growth model integrates information from genetic and biological data of
      the patients. The SMARTool system enables also the calculation of the virtual
      functional assessment index (vFAI), an index equivalent to the invasively
      measured fractional flow reserve (FFR), to provide decision support for patients
      with stenosed arteries. Finally, it integrates modeling of stent deployment. In
      this work preliminary results are presented. More specifically, the
      reconstruction methodology has mean value of Dice Coefficient and Hausdorff
      Distance is 0.749 and 1.746, respectively, while low ESS and high LDL
      concentration can predict plaque progression.

PMID- 29059820
TI  - Coronary artery disease detection using photoplethysmography.
AB  - This paper presents a technique for coronary artery disease (CAD) detection
      through photoplethysmography (PPG). This work is aimed at developing a non
      invasive, inexpensive screening technique suitable for home monitoring. Time
      domain analysis of PPG signal and its second derivative has been carried out to
      extract distinguishing features. Support Vector Machine based classifier has been
      used to classify CAD patients. ICU patient data from MIMIC-II dataset has been
      used for performance evaluation. Sensitivity of 85% and specificity of 78% has
      been achieved for the analysed data.

PMID- 29059821
TI  - Computationally efficient algorithm for photoplethysmography-based atrial
      fibrillation detection using smartphones.
AB  - Atrial fibrillation (AF) is one of the major causes of stroke, heart failure,
      sudden death, and cardiovascular morbidity and the most common type of
      arrhythmia. Its diagnosis and the initiation of treatment, however, currently
      requires electrocardiogram (ECG)-based heart rhythm monitoring. The
      photoplethysmogram (PPG) offers an alternative method, which is convenient in
      terms of its recording and allows for self-monitoring, thus relieving clinical
      staff and enabling early AF diagnosis. We introduce a PPG-based AF detection
      algorithm using smartphones that has a low computational cost and low memory
      requirements. In particular, we propose a modified PPG signal acquisition,
      explore new statistical discriminating features and propose simple classification
      equations by using sequential forward selection (SFS) and support vector machines
      (SVM). The algorithm is applied to clinical data and evaluated in terms of
      receiver operating characteristic (ROC) curve and statistical measures. The
      combination of Shannon entropy and the median of the peak rise height achieves
      perfect detection of AF on the recorded data, highlighting the potential of PPG
      for reliable AF detection.

PMID- 29059822
TI  - A novel method for accurate estimation of HRV from smartwatch PPG signals.
AB  - Photoplethysmography(PPG) as a non-invasive tool for monitoring various
      cardiovascular parameters, has become popular due to the ease of wearable
      integration and pervasive nature. Due to unobtrusive nature of sensor placement
      at wrist, smartwatches and wrist based fitness bands have gained popularity.
      However, any movement of the wrist along with frequent loose contacts
      significantly corrupts the PPG signal. Reliable peak detection from the corrupted
      PPG signal is essential for any further processing, as many physiological
      quantities such as heart rate variability (HRV) depends on the peak-to-peak
      distances in the PPG signal, known as the RR Series. This paper attempts to
      provide a robust algorithm for peak detection in noise & motion artefact
      corrupted PPG signals. The algorithm consists of steps to remove the baseline
      drift in the PPG signal using wavelet filtering and trend removal and subsequent
      peak detection using autocorrelation for each pseudo-periodic segment of the
      signal. The validation of the method is done by comparing the PPG peaks detected
      by the algorithm with RR series extracted from simultaneously captured ECG
      signal.

PMID- 29059823
TI  - Cardiac arrhythmia detection using photoplethysmography.
AB  - Cardiovascular Diseases (CVDs) cause a very large number of casualties around the
      world every year and cardiac arrhythmias contribute to significant proportion of
      CVD related deaths. Bedside cardiac activity monitors in hospitals are based on
      electrocardiogram (ECG) processing and are known to produce too many false
      alarms. Moving beyond bedside care, ECG is not very suitable for use in wearable
      devices. Photoplethysmography (PPG) on the other hand provides an inexpensive and
      more wearable device-friendly alternative. This work presents a technique to
      detect life threatening arrhythmias using only PPG waveforms. PhysioNet Challenge
      2015 data is used to detect five types of arrhythmias namely, tachycardia,
      bradycardia, asystole, ventricular tachycardia and ventricular fibrillation. A
      novel technique is employed to assign pulse quality index to every PPG pulse and
      highest quality portion of the signal is used for detection. Results indicate
      that PPG provides a viable alternative for conventional ECG based detection. An
      overall true positive rate (TPR) of 93% was achieved with true negative rate
      (TNR) of 53.78% suggesting that PPG is a viable option for arrhythmia detection.

PMID- 29059824
TI  - Photoplethysmography beat detection and pulse morphology quality assessment for
      signal reliability estimation.
AB  - Photoplethysmography (PPG) is one of the key technologies for unobtrusive
      physiological monitoring, with ongoing attempts to use it in several medical
      fields, ranging from night to night sleep analysis to continuous cardiac
      arrhythmia monitoring. However, the PPG signals are susceptible to be corrupted
      by noise and artifacts, caused, e.g., by limb or sensor movement. These artifacts
      affect the morphology of PPG waves and prevent the accurate detection and
      localization of beats and subsequent cardiovascular feature extraction. In this
      paper a new algorithm for beat detection and pulse quality assessment is
      described. The algorithm segments the PPG signal in pulses, localizes each beat
      and grades each segment with a quality index. The obtained index results from a
      comparison between each pulse and a template derived from the surrounding pulses,
      by mean of dynamic time warping barycenter averaging. The quality index is used
      to discard corrupted pulse beats. The algorithm is evaluated by comparing the
      detected beats with annotated PPG signals and the results are published over the
      same data. The described method achieves an improved sensitivity and a higher
      predictive value.

PMID- 29059825
TI  - Enhanced detection of sleep apnoea using heart-rate, respiration effort and
      oxygen saturation derived from a photoplethysmography sensor.
AB  - This paper presents a study on identifying sleep apnoea using the
      photoplethysmography (PPG) measurements, which is obtained from the SpO2 sensor.
      Using a database of polysomnogram (PSG) records of 52 patients, the heart rate
      and breathing effort information was derived from the PPG measurements and then
      features are extracted and processed by a classifier to detect one-minute epochs
      of sleep apnoea. The ground truth labels for the epochs were determined by
      trained technicians using the full PSG signal. Pulse oximetry (SpO2) measurements
      from the same sensor are also used in the classification process for comparison
      and in combination with the PPG results. The results show that both the heart
      rate and respiratory effort information derived from the PPG signal were able to
      detect apnoeic epochs with some success. The best classification performance of
      87% for correctly labelling the epochs was obtained when the SpO2 features and
      the PPG features were combined.

PMID- 29059826
TI  - An elderly fall detection using a wrist-worn accelerometer and barometer.
AB  - As the world population is growing toward an aging society, elderly fall becomes
      a serious problem. Automatic fall detection and alert systems could shorten their
      waiting time after a fall and mitigate its physical and mental negative
      consequences. This work proposes a method that integrates a 3-axis accelerometer
      and a barometer on a wrist-worn device for the fall detection task. The method
      focuses on the use of noisy signals from a barometer in both pre-processing steps
      and feature extractions. A use of free falling events to address the lack of
      training data in a learning process is also explored. An evaluation using
      simulated falls and various activities shows a high classification performance
      except for a few false alarms occurring when sitting on the floor from a standing
      pose.

PMID- 29059827
TI  - Using measurements from wearable sensors for automatic scoring of Parkinson's
      disease motor states: Results from 7 patients.
AB  - The objective of this study was to investigate the validity of an objective gait
      measure for assessment of different motor states of advanced Parkinson's disease
      (PD) patients. Seven PD patients performed a gait task up to 15 times while
      wearing sensors on their upper and lower limbs. Each task was performed at
      specific points during a test day, following a single dose of levodopa-carbidopa.
      At the time of the tasks the patients were video recorded and three movement
      disorder experts rated their motor function on three clinical scales: a treatment
      response scale (TRS) that ranged from -3 (very bradykinetic) to 0 (ON) to +3
      (very dyskinetic), a dyskinesia score that ranged from 0 (no dyskinesia) to 4
      (extreme dyskinesia), and a bradykinesia score that ranged from 0 (no
      bradykinesia) to 4 (extreme bradykinesia). Raw accelerometer and gyroscope data
      of the sensors were processed and analyzed with time series analysis methods to
      extract features. The utilized features quantified separate limb movements as
      well as movement symmetries between the limbs. The features were processed with
      principal component analysis and the components were used as predictors for
      separate support vector machine (SVM) models for each of the three scales. The
      performance of each model was evaluated in a leave-one-patient out setting where
      the observations of a single patient were used as the testing set and the
      observations of the other 6 patients as the training set. Root mean square error
      (RMSE) and correlation coefficients for the predictions showed a good ability of
      the models to map the sensor data into the rating scales. There were strong
      correlations between the SVM models and the mean ratings of TRS (0.79;
      RMSE=0.70), bradykinesia score (0.79; RMSE=0.47), and bradykinesia score (0.78;
      RMSE=0.46). The results presented in this paper indicate that the use of wearable
      sensors when performing gait tasks can generate measurements that have a good
      correlation to subjective expert assessments.

PMID- 29059828
TI  - Artifact detection in accelerometer signals acquired from the carotid.
AB  - Manual pulse palpation is the common procedure to assess pulse in unconscious
      patients. This is an error prone procedure during cardiopulmonary resuscitation
      and therefore automatic pulse detection techniques are being investigated.
      Accelerometry is an interesting sensing modality for this type of applications.
      However, accelerometers are highly prone to movement artifacts. Hence, one
      challenge in designing a solution using accelerometers is to handle motion
      artifacts properly. In this paper we investigate computationally simple features
      and classifier to capture movement artifacts in accelerometer signals acquired
      from the carotid. In particular, based on data obtained from health subjects we
      show that it is possible to use simple features to achieve an artifact detection
      sensitivity and specificity higher than 90%.

PMID- 29059829
TI  - Development of a wearable plantar force measurement device for gait analysis in
      remote conditions.
AB  - The pressure field that exists between the foot and the supporting surface is
      identified as the foot plantar pressure. The information obtained from foot
      plantar pressure measurements has useful applications that include diagnosis of
      gait disturbances, optimization of footwear design, sport biomechanics and
      prevention of injury. Using wearable technology to measure foot plantar pressure
      continuously allows the collection of comprehensive real-life data sets while
      interfering minimally with the subject's daily activities. This paper presents
      the design of a wearable device to measure foot plantar pressure. Mechanical and
      electrical design considerations as well as data analysis are discussed. A pilot
      study involving 20 physically fit volunteers (15 males and 5 females, ageing from
      20 - 45) performing a variety of physical activities (such as standing, walking,
      jumping and climbing up and down stairs) illustrate the potential of the device
      in terms of its wearability, and suitability for unobtrusive long-term
      monitoring.

PMID- 29059830
TI  - Weakly-supervised learning for Parkinson's Disease tremor detection.
AB  - Continuous, automated monitoring of Parkinsons Disease (PD) symptoms would
      provide clinicians with more information to understand their patients' disease
      progression and adjust treatment protocols, thereby improving PD care. Collecting
      precisely labeled data for Parkinson's symptoms, such as tremor, is difficult.
      Therefore, algorithms for monitoring should only require weakly-labeled training
      data. In this paper, we evaluate five standard weakly-supervised algorithms and
      propose a "stratified" version of three of the algorithms, which take advantage
      of knowing the approximate amount of tremor within each segment. In particular,
      we analyze PD tremor detection performance as training segments increase in
      length from 30 seconds to 10 minutes, and labels thereby become less precise. As
      segment length increases to 10 minutes, standard algorithms are not able to
      discriminate tremor from non-tremor. However, our stratified algorithms, which
      can make use of more nuanced labels, show little decrease in performance as
      segment length increases.

PMID- 29059831
TI  - Real-time gait analysis with accelerometer-based smart shoes.
AB  - In this paper, we present the evaluation of a new smart shoe capable of
      performing gait analysis in real time. The system is exclusively based on
      accelerometers which minimizes the power consumption. The estimated parameters
      are activity class (rest/walk/run), step cadence, ground contact time, foot
      impact (zone, strength, and balance), forward distance, and speed. The different
      parameters have been validated with a customized database of 26 subjects on a
      treadmill and video data labeled manually. Key measures for running analysis such
      as the cadence is retrieved with a maximum error of 2%, and the ground contact
      time with an average error of 3.25%. The classification of the foot impact zone
      achieves a precision between 72% and 91% depending of the running style. The
      presented algorithm has been licensed to ICON Health & Fitness Inc. for their
      line of wearables under the brand iFit.

PMID- 29059832
TI  - End-inspiratory occlusion in the presence of intrinsic PEEP.
AB  - Typical modern mechanical ventilators offer the clinician the possibility of
      automatically performing end-inspiratory occlusion maneuvers. The static
      conditions induced by such maneuvers are indeed favorable to estimating patient's
      respiratory mechanics in terms of total resistance (R) and elastance (E). These
      are parameters of wide clinical interest. However, in the presence of intrinsic
      PEEP, the standard formula used to compute E via the occlusion maneuver is known
      to be inaccurate. In this paper we propose an alternative method for the
      estimation of E via the occlusion maneuver that eliminates the bias by leveraging
      concepts derived from physiological modeling of the respiratory system dynamics.
      The proposed method is also capable of accounting for respiratory efforts
      triggering the breath, and hence can be applied in both passive and spontaneously
      breathing conditions.

PMID- 29059833
TI  - Two-parameter leak estimation in non-invasive ventilation.
AB  - In this paper we present a method for the estimation of leaks in non-invasive
      ventilation. Accurate estimation of leaks is a key component of a ventilator,
      since it determines the ventilator performance in terms of patient-ventilator
      synchrony and air volume delivery. In particular, in non-invasive ventilation,
      the patient flow is significantly different from the flow measured at the
      ventilator outlet. This is mostly due to the vent orifice along the tube that is
      used for exhalation, but also to the non-intentional leaks that occur elsewhere
      in the circuit (e.g., at the mask). Such leaks are traditionally quantified via a
      model with two parameters, but only one of them is continually updated - the
      other is fixed. The new algorithm allows for breath-by-breath update of both
      parameters. This was made possible by leveraging a model describing the patient
      respiratory mechanics.

PMID- 29059834
TI  - Electrical properties of phantoms for mimicking breast tissue.
AB  - In order to test and calibrate an EIT (Electrical Impedance Tomography) system,
      many researchers rely on phantoms mimicking breast tissues. These phantoms are
      usually made of saline solutions, agar and/or vegetables, allowing the user to
      set the conductivity of the material by changing the salt concentration. Due to
      that fact that the dispersion behavior in the vicinity of megahertz is
      fundamental to detect carcinoma, this work aims to propose a phantom composed by
      a mixture of agar and gelatin (emulating the normal tissue) and a piece of carrot
      (emulating the carcinoma). It also investigates the frequency dependence from 1
      to 10,000 kHz. The proposed phantom showed capability to mimic some absolute and
      relative electrical parameters used to detect cancer according to the literature.
      The differences in the impedance modulus were found to be more dispersive in the
      mimic carcinoma tissue type than the normal mimic one. It is simple to prepare,
      low cost, has similar electrical properties to the ones that have been used in
      the literature, better mechanical properties and longer life time. It can be
      concluded that gelatin-agar gel may have a high potential to be used as a breast
      tissue phantom.

PMID- 29059835
TI  - Central sulcus development in early childhood.
AB  - Mapping out the development of the brain in early childhood is a critical part of
      understanding neurological disorders. The brain grows rapidly in early life,
      reaching 95% of the final volume by age 6. A normative atlas containing
      structural parameters that indicate development would be a powerful tool in
      understanding the progression of neurological diseases. Although some studies
      have begun exploring cortical development in pediatric imaging, sulci have not
      been examined extensively. Here, we study the changes in the Central Sulcus (CS),
      which is one of the earliest sulci to develop from the fetal stage, at early
      developmental age 1-3 years old using high resolution magnetic resonance images.
      Parameterization of the central sulcus was performed and results show us that the
      CS change corresponds to the development of the mouth and tongue regions.

PMID- 29059836
TI  - Design of patient-specific concentric tube robots using path planning from 3-D
      ultrasound.
AB  - Percutaneous techniques and robot-assisted surgical systems have enabled
      minimally invasive procedures that offer reduced scarring, recovery time, and
      complications compared to traditional open surgeries. Despite these improvements,
      access to diseased sites using the standard, straight needle-based percutaneous
      techniques is still limited for certain procedures due to intervening tissues.
      These limitations can be further exacerbated in specific patient groups,
      particularly pediatric patients, whose anatomy does not fit the traditional tools
      and systems. We therefore propose a patient-specific paradigm to design and
      fabricate dexterous, robotic tools based on the patient's preoperative images. In
      this paper, we present the main steps of our proposed paradigm - image-based path
      planning, robot design, and fabrication - along with an example case that focuses
      on a class of dexterous, snake-like tools called concentric tube robots. We
      demonstrate planning a safe path using a patient's preoperative ultrasound
      images. We then determine the concentric tube robot parameters needed to achieve
      this path, and finally, we use 3-D printing to fabricate the patient-specific
      robot.

PMID- 29059837
TI  - Cranial ultrasound-based prediction of post hemorrhagic hydrocephalus outcome in
      premature neonates with intraventricular hemorrhage.
AB  - Premature neonates with intraventricular hemorrhage (IVH) followed by post
      hemorrhagic hydrocephalus (PHH) are at high risk for brain injury. Cranial
      ultrasound (CUS) is used for monitoring of premature neonates during the first
      weeks after birth to identify IVH and follow the progression to PHH. However, the
      lack of a standardized method for CUS evaluation has led to significant
      variability in decision making regarding treatment. We propose a quantitative
      imaging tool for the evaluation of PHH on CUS for premature neonates based on
      morphological features of the cerebral ventricles. We retrospectively studied 64
      extremely premature neonates born less than 29 weeks gestational age, less than
      1,500 grams weight at birth, admitted to our center within two weeks of life, and
      diagnosed with different grades of IVH. We extracted morphological features of
      the lateral ventricles from CUS imaging using image analysis techniques to
      compare neonates who needed a temporizing intervention to treat PHH to the ones
      who did not. From the original set of features, an optimal ranking was obtained
      based on linear support vector machine. A subset of features was subsequently
      selected that maximizes the overall accuracy level. Regarding whether or not
      there was a need for temporizing intervention, we predicted the outcome of PHH
      with an improved accuracy level of 84%, compared to the 76% rate obtained by
      linear manual measurement. The proposed imaging tool allowed us to establish a
      quantitative method for PHH evaluation on CUS in extremely premature neonates
      with IVH. Further studies will help standardize the evaluation of CUS in those
      neonates to institute treatments earlier and improve outcomes.

PMID- 29059838
TI  - A low power flash-FPGA based brain implant micro-system of PID control.
AB  - In this paper, we demonstrate that a low power flash FPGA based micro-system can
      provide a low power programmable interface for closed-loop brain implant inter-
      faces. The proposed micro-system receives recording local field potential (LFP)
      signals from an implanted probe, performs closed-loop control using a first order
      control system, then converts the signal into an optogenetic control stimulus
      pattern. Stimulus can be implemented through optoelectronic probes. The long term
      target is for both fundamental neuroscience applications and for clinical use in
      treating epilepsy. Utilizing our device, closed-loop processing consumes only
      14nJ of power per PID cycle compared to 1.52MUJ per cycle for a micro-controller
      implementation. Compared to an application specific digital integrated circuit,
      flash FPGA's are inherently programmable.

PMID- 29059839
TI  - Smart mat system with pressure sensor array for unobtrusive sleep monitoring.
AB  - To improve the unobtrusiveness and comfortableness of sleep monitoring, we
      proposed the design and implementation of a smart mat which utilized flexible
      pressure sensor array and printed electrodes to monitor physiological and
      behavioral data during sleep. With the proposed novel soft seven-layer structure,
      the smart mat system can measure pressure distribution images and calculate
      respiratory rate of subjects. The function of this system was realized with
      pressure acquisition circuit controlled by Arduino processor. Experiments for
      pressure distribution tests and respiratory rate measurements were carried out to
      validate the performance of the proposed system. The experimental results
      demonstrated that the smart mat could be a viable option for unobtrusive sleep
      monitoring in the future.

PMID- 29059840
TI  - Design of a microfluidic paper-based device for analysis of biomarkers from urine
      samples on diapers.
AB  - Among all infections, urinary tract infections (UTI) are one of the most common.
      Nowadays the procedures to analyze urine and consequently detect UTI are often
      painful and time-consuming. Recent studies about microfluidic paper-based devices
      have developed the interest of researchers due their outstanding characteristics.
      In this paper is presented a novel design for a microfluidic paper-based device
      for screening and analysis of multiple biomarkers from urine samples on diapers.
      The device consists on a set of eight layers. It was designed based on the
      previous attempts to improve and overcome some problems detected as the
      continuous entrance of fluids, the possibility of contamination and the
      invalidity of results due to communication between different reagent pads. One
      approach was create a "self-locking" mechanism that closes the sample inlet in
      approximately four minutes solving the first two problems. Furthermore, is
      important that comfort is guaranteed, hence a device with a total thickness of
      5,3 mm is presented. This device can keep the results for eight hours and can be
      used as a low-cost and more effective alternative than conventional methods being
      a strategy with potential for the diagnostic and analysis of biological samples
      in the future improving healthcare.

PMID- 29059841
TI  - Stability of colorimetric results in the detection of urine biomarkers using a
      paper-based analytical device.
AB  - Urinalysis allows obtaining information about many of the body's functions.
      Normally, urine is a very easily collected specimen, but in some cases, it can be
      an uncomfortable process. Moreover, standard methods such as microscopic
      examination or urine culturing represent time-consuming procedures. In this
      regard, this work explores the design of a device that combines disposable
      diapers, as a platform for sample collection, with part of the dipsticks method.
      Even though this is a desirable combination for a faster and comfortable
      approach, it is also convenient to extend the prescribed time, provided by the
      dipstick manufacturer, to read the results. This allows the stability and
      validity of the results for longer, preferably until the moment of the diaper
      changing, and it was also considered in the design. The desired conditions were
      reproduced for the reagent pads of glucose and nitrite. The results show that the
      RGB profile, obtained in glucose detection, varied after approximately 60 min.
      However, when the developed colors are visually compared with the reference
      colors, the results suggest that there were not significant variations. In the
      nitrite assay, by analyzing the RGB profile or by visual comparison with the
      reference colors, the color does not appear to change over time, but the results
      were not the expected. It seems that the proposed design is promising regarding
      results stability, but more experiments need to be done to check if the
      variations are constant for more biomarkers in the conditions provided by the
      device.

PMID- 29059842
TI  - Injection moulded microneedle sensor for real-time wireless pH monitoring.
AB  - This paper describes the development of an array of individually addressable pH
      sensitive microneedles using injection moulding and their integration within a
      portable device for real-time wireless recording of pH distributions in
      biological samples. The fabricated microneedles are subjected to gold patterning
      followed by electrodeposition of iridium oxide to sensitize them to 0.07 units of
      pH change. Miniaturised electronics suitable for the sensors readout, analog-to
      digital conversion and wireless transmission of the potentiometric data are
      embodied within the device, enabling it to measure real-time pH of soft
      biological samples such as muscles. In this paper, real-time recording of the
      cardiac pH distribution, during ischemia followed by reperfusion cycles in
      cardiac muscles of male Wistar rats has been demonstrated by using the
      microneedle array.

PMID- 29059843
TI  - Carbon nanospikes for biosensing applications.
AB  - In this paper, we discuss the structure and characteristics of carbon nanospikes.
      We also compare carbon nanospikes with previously grown carbon nanostructures
      known as vertically aligned carbon nanofibers (VACNF). Plasma enhanced chemical
      vapor deposition (PECVD) is used to fabricate both the nanospikes and VACNF.
      However, carbon nanospikes do not require a catalyst for the growth process,
      whereas VACNF requires a catalyst in the growth process. This facilitates batch
      fabrication with greater reproducibility. Scanning electron microscope images and
      Raman spectroscopy show that carbon nanospikes fabricated on silver wires will
      show superior performance.

PMID- 29059844
TI  - Multiscale decoding for reliable brain-machine interface performance over time.
AB  - Recordings from invasive implants can degrade over time, resulting in a loss of
      spiking activity for some electrodes. For brain-machine interfaces (BMI), such a
      signal degradation lowers control performance. Achieving reliable performance
      over time is critical for BMI clinical viability. One approach to improve BMI
      longevity is to simultaneously use spikes and other recording modalities such as
      local field potentials (LFP), which are more robust to signal degradation over
      time. We have developed a multiscale decoder that can simultaneously model the
      different statistical profiles of multi-scale spike/LFP activity (discrete spikes
      vs. continuous LFP). This decoder can also run at multiple time-scales
      (millisecond for spikes vs. tens of milliseconds for LFP). Here, we validate the
      multiscale decoder for estimating the movement of 7 major upper-arm joint angles
      in a non-human primate (NHP) during a 3D reach-to-grasp task. The multiscale
      decoder uses motor cortical spike/LFP recordings as its input. We show that the
      multiscale decoder can improve decoding accuracy by adding information from LFP
      to spikes, while running at the fast millisecond time-scale of the spiking
      activity. Moreover, this improvement is achieved using relatively few LFP
      channels, demonstrating the robustness of the approach. These results suggest
      that using multiscale decoders has the potential to improve the reliability and
      longevity of BMIs.

PMID- 29059845
TI  - An unsupervised learning algorithm for multiscale neural activity.
AB  - Technological advances have enabled the simultaneous recording of multiscale
      neural activity consisting of spikes, local field potential (LFP), and
      electrocorticogram (ECoG). Developing models that describe the encoding of
      behavior within multiscale activity is essential both for understanding neural
      mechanisms and for various neurotechnologies such as brain-machine interfaces
      (BMI). Multiscale recordings consist of signals with different statistical
      profiles and time-scales. While encoding models have been developed for each
      scale of activity alone, developing statistical models that simultaneously
      characterize discrete spike and continuous LFP/ECoG recordings and their various
      time-scales is a major challenge. To address this challenge, we have recently
      proposed a multiscale state-space encoding model for combined spike/LFP/ECoG
      recordings. However, methods to learn these state-space models from data are
      still lacking. Here, we develop an unsupervised learning algorithm for multiscale
      state-space models. Given a multiscale dataset, our algorithm finds the maximum
      likelihood estimate of the state-space model parameters using a new expectation
      maximization (EM) technique. We show that the new algorithm can learn the
      encoding model accurately from simulated multiscale data. We also show that the
      learned model can be used to decode arm movement trajectories from simulated
      multiscale activity. These multiscale models have the potential to improve the
      performance and robustness of various neurotechnologies.

PMID- 29059846
TI  - Electromyographic Bridge-a multi-movement volitional control method for
      functional electrical stimulation: prototype system design and experimental
      validation.
AB  - The voluntary participation of the paralyzed patients is crucial for the
      functional electrical stimulation (FES) therapy. In this study, we developed a
      strategy called "EMG Bridge" (EMGB) for volitional control of multiple movements
      using FES technique. The surface electromyography (sEMG) signals of the agonist
      muscles were transformed to stimulation pulses with various pulse width and
      frequency to stimulate the target paralyzed muscles using MAV/NSS co-modulation
      (MNDC) algorithm we proposed recently. Motion pattern classification based on
      linear discriminant analysis (LDA) was included to recognize the motion status
      and mapping the sEMG detection channel to the corresponding stimulation channel.
      A prototype EMGB system was built for real-time control of four hand movements.
      The test results showed that the movements can be reproduced with a successful
      rate of 92.5+/-3.5%. The angle trajectory of wrist joint and metacarpal
      phalangeal joint can be mimicked with a maximum cross-correlation coefficient >
      0.84 and a latency less than 300 ms.

PMID- 29059847
TI  - Low-intensity focused ultrasound stimulator using focal depth controller for
      improved targeting in neuromuscular rehabilitation.
AB  - Low-intensity ultrasound can be used for noninvasive neuromuscular stimulation to
      enhance the recovery of injured peripheral nerves and muscles. In order to
      improve the stimulation efficiency, focused ultrasound (FUS) with a high energy
      density should be used. Because the FUS is concentrated at a miniaturized focal
      area, deliberate targeting with focal depth control is required to achieve the
      accurate stimulation. In this study, a low-intensity focused ultrasound (LIFU)
      stimulator with a focal depth controller is presented as an effective ultrasound
      stimulation system for the neuromuscular rehabilitation. In the developed
      stimulator, the target depth is adjusted by the focal depth controller with the
      brief structure. The experimental results show that the developed stimulator can
      generate the high quality LIFU stimulation with the spatial average-pulse average
      intensity (ISAPA) of 496 mW/cm2, which is sufficient to improve the
      rehabilitation of injured peripheral nerves and muscles. In the in vivo
      experiment, a rat's sciatic nerve was successfully targeted by the developed
      stimulator. These results indicate that the developed stimulator can be used to
      improve the quality of the ultrasound stimulation for neuromuscular
      rehabilitation by targeting a specific area.

PMID- 29059848
TI  - Towards a wearable hand exoskeleton with embedded synergies.
AB  - Numerous hand exoskeletons have been proposed in the literature with the aim of
      assisting or rehabilitating victims of stroke, brain/spinal cord injury, or other
      causes of hand paralysis. In this paper a new 3D printed soft hand exoskeleton,
      HEXOES (Hand Exoskeleton with Embedded Synergies), is introduced and mechanically
      characterized. Metacarpophalangeal (MCP) and proximal
      interphalangeal/interphalangeal (PIP/IP) joints had measured maximum flexion
      angles of 53.7 +/- 16.9 degrees  and 39.9 +/- 13.4 degrees , respectively; and
      maximum MCP and PIP angular velocities of 94.5 +/- 41.9 degrees/s and 74.6 +/-
      67.3 degrees/s, respectively. These estimates indicate that the mechanical design
      has range of motion and angular velocity characteristics that meet the
      requirements for synergy-based control. When coupled with the proposed control
      loop, HEXOES can be used in the future as a test-bed for synergy-based clinical
      hand rehabilitation.

PMID- 29059849
TI  - An integrated multichannel neural recording analog front-end ASIC with area
      efficient driven right leg circuit.
AB  - This paper describes an integrated multichannel neural recording analog front end
      (AFE) with a novel area-efficient driven right leg (DRL) circuit to improve the
      system common mode rejection ratio (CMRR). The proposed AFE consists of an AC
      coupled low-noise programmable-gain amplifier, an area-efficient DRL block and a
      10-bit SAR ADC. Compared to conventional DRL circuit, the proposed capacitor-less
      DRL design achieves 90% chip area reduction with enhanced CMRR performance,
      making it ideal for multichannel biomedical recording applications. The AFE
      circuit has been designed in a standard 0.18-MUm CMOS process. Post-layout
      simulation results show that the AFE provides two gain settings of 54dB/60dB
      while consuming 1 MUA per channel under a supply voltage of 1 V. The input
      referred noise of the AFE integrated from 1 Hz to 10k Hz is only 4 MUVrms and the
      CMRR is 110 dB.

PMID- 29059851
TI  - A handheld device for magnetically inserting a neural interface into a peripheral
      nervous system.
AB  - This paper proposes a compact handheld device for magnetically inserting a neural
      interface into a peripheral nervous system (PNS). Users can pull and hold a
      flexible peripheral nerve (e.g., sciatic nerve) at the front of the device for
      the accurate and stable targeting process. The device automatically inserts a
      neural interface using magnetic impacts that are generated by a miniature motor
      and a pair of magnets. We investigate the characteristics of the employed
      mechanism, and present the preliminary experimental results.

PMID- 29059850
TI  - Rodent wearable ultrasound system for wireless neural recording.
AB  - Advances in minimally-invasive, distributed biological interface nodes enable
      possibilities for networks of sensors and actuators to connect the brain with
      external devices. The recent development of the neural dust sensor mote has shown
      that utilizing ultrasound backscatter communication enables untethered sub-mm
      neural recording devices. These implanted sensor motes require a wearable
      external ultrasound interrogation device to enable in-vivo, freely-behaving
      neural interface experiments. However, minimizing the complexity and size of the
      implanted sensors shifts the power and processing burden to the external
      interrogator. In this paper, we present an ultrasound backscatter interrogator
      that supports real-time backscatter processing in a rodent-wearable, completely
      wireless device. We demonstrate a generic digital encoding scheme which is
      intended for transmitting neural information. The system integrates a front-end
      ultrasonic interface ASIC with off-the-shelf components to enable a highly
      compact ultrasound interrogation device intended for rodent neural interface
      experiments but applicable to other model systems.

PMID- 29059852
TI  - Unidirectional ephaptic stimulation between two myelinated axons.
AB  - Providing realistic sensory feedback for prosthetic devices strongly relies on an
      accurate modelling of machine-nerve interfaces. Models of these interfaces in the
      peripheral nervous system usually neglect the effects that ephaptic coupling can
      have on the selectivity of stimulating electrodes. In this contribution, we study
      the ephaptic stimulation between myelinated axons and show its relation with the
      separation between fibers and the conductivity of the medium that surrounds them.

PMID- 29059853
TI  - Novel integration and packaging concepts of highly miniaturized inductively
      powered neural implants.
AB  - This work proposes solutions to the current bulky packaged neural implants. We
      describe the next generation of miniaturized wirelessly powered neural interface
      that are distributed and free floating in the nervous system. This paper focuses
      on the microassembly, hermetic packaging and its effect on the inductive power
      link.

PMID- 29059854
TI  - Design of contact zone topography for implantable high-channel electrical
      connectors.
AB  - Detachable high-channel electrical connections pose a bottleneck on the path to
      active implants with higher numbers of electrode contacts and miniaturized
      geometries. Not only low-resistance, reproducible and reliable contacts have to
      be realized but also seals that ensure electrical insulation in the harsh body
      environment. Using planar contact arrangements one can resort to laser
      microprocessing leading to minimal size connectors. However, this poses the need
      to carefully design the topographies within the contact zone. In this study, we
      assess different methods to design the topography of planar contact pad arrays.
      Using topographical analysis and evaluation of electrical functionality,
      influential mechanisms were identified and two functional ones have been
      selected.

PMID- 29059855
TI  - Difference in voice analysis result by pre- and post- processing of telephone
      line.
AB  - The purpose of this study is to verify the impact of a deterioration of the sound
      quality of voice by a telephone line on estimating Vitality as the extent of
      depressive tendency based on voice analysis using MIMOSYS. First, the voices of
      about 1,000 people recorded using a recorder were prepared. Next, each voice was
      coded and resampled in preparation for transmission over a phone line. Vitalities
      obtained by analyzing the voices before and after these processes were compared.
      The results showed high correlation between the Vitality after coding and
      Vitality before coding, revealing that using a telephone would be an effective
      way to obtain voices.

PMID- 29059856
TI  - Reproducibility of photoplethysmography-based local pulse transit time
      measurement.
AB  - There are several previously published approaches of measuring local pulse
      transit time (PTT). One of these approaches is to use two optical sensors based
      on photoplethysmography (PPG). However, little information about reproducibility
      in PPG based PTT measurement is available. Therefore, we performed a small sample
      size study (n = 5) to investigate quantitative criteria for reproducible PTT
      measurement. The inflection point as a characteristic feature of the pulse wave
      showed the most stabile results under varying conditions. Furthermore, we found
      that correlation between related pulse waves could be used as a threshold for
      signal quality. We suggest to implement a real-time operator feedback based on
      the found criteria to ensure reproducible PTT measurements.

PMID- 29059857
TI  - Pulse arrival time (PAT) measurement based on arm ECG and finger PPG signals -
      comparison of PPG feature detection methods for PAT calculation.
AB  - In this study, pulse arrival time (PAT) was measured using a simple measurement
      setup consisting of arm electrocardiogram (ECG) and finger photoplethysmogram
      (PPG). Four methods to calculate PAT from the measured signals were evaluated.
      PAT was calculated as the time delay between ECG R peak and one of the following
      points in the PPG waveform: peak (maximum value of PPG waveform), foot (minimum
      value of PPG waveform), dpeak (maximum value of the first derivative of PPG
      waveform) and ddpeak (maximum value of the second derivative of PPG waveform). In
      addition to PAT calculation, pulse period (PP) intervals based on the detected
      features were determined and compared to RR intervals derived from ECG signal.
      Based on the results obtained here, the most promising method to be used in PAT
      or PP calculation seems to be the dpeak detection method.

PMID- 29059858
TI  - Pulse arrival time measurement with coffee provocation.
AB  - This study investigated the effect of coffee intake in pulse arrival time (PAT)
      and pulse wave velocity (PWV) measured with electrocardiogram (ECG) from arms and
      photoplethysmogram (PPG) from fingertip. In addition, correlation of PWV with
      blood pressure (BP) is analyzed. 30 healthy participants were recruited to two
      measurement sessions, one arranged before and another one after the coffee
      intake. During each session, ECG and PPG were measured continuously for six
      minutes and PAT values calculated from ECG R-peak to the maximum of the first
      derivative of the PPG pulse. In addition, blood pressure was measured twice
      during each session with cuff based method. Coffee intake had statistically
      significant influence on both systolic and diastolic blood pressure, but not on
      PAT or PWV. Correlation between systolic blood pressure and PWV was 0.44.
      Individual calibration, additional derivatives of ECG and PPG such as heart rate,
      pulse pressure, or waveform characteristics could improve the correlation.

PMID- 29059859
TI  - Increased arterial stiffness does not respond to renal denervation in an animal
      model of secondary hypertension.
AB  - Renal denervation is a novel device based therapy promoted to reduce high blood
      pressure. We examined the impact of renal denervation on systolic blood pressure,
      renal function, and arterial stiffness in the Lewis Polycystic Kidney disease
      (LPK) rodent model of kidney disease. Animals were subjected to bilateral renal
      denervation or sham surgeries at age 6 and 12 weeks. Systolic blood pressure was
      monitored by tail-cuff plethysmography and renal function by urinalysis and
      creatinine clearance. At age 16 weeks, beat-to-beat aortic pulse wave velocity as
      a functional indicator of arterial stiffness was determined. Renal denervation
      produced an overall reduction in blood pressure in the LPK [(denervated 164+/-4
      vs. sham-operated 180+/-6 mmHg, n = 6 per group, P=0.003)] and delayed, but did
      not prevent, the decline in renal function. Aortic pulse wave velocity was
      markedly elevated in the LPK compared with Lewis and was not altered by renal
      denervation in the LPK however a reduction was seen in the control Lewis animals.
      These results support the hypothesis that renal nerves contribute to secondary
      hypertension in conditions such as kidney disease.

PMID- 29059860
TI  - Brachial artery stiffness estimation using ARTSENS.
AB  - Central and peripheral arteries stiffening prominently affect hemodynamics thus
      increasing the risk of coronary heart disease, chronic kidney disease and end
      stage renal disease. There are several commercially available non-invasive
      measurement technologies for the evaluation of stiffness that are expensive,
      demand dedicated expertise and fall short for mass screening. Considering this,
      we have developed ARTSENS(r), a highly compact and portable image-free ultrasound
      device for evaluation of arterial stiffness. The capability of the device to
      perform accurate measurements of carotid artery stiffness has been validated
      through extensive in-vivo studies. In this paper we demonstrate the feasibility
      of using ARTSENS(r) for measuring brachial artery stiffness. An inter-operator
      repeatability study was done based on in-vivo experiments on 9 young healthy
      subjects. The study included measurement of distension, end diastolic lumen
      diameter, arterial compliance and stiffness index performed both on carotid
      artery and brachial artery by two operators successively. The degree of agreement
      between the measurements made by operators has been investigated based on Bland
      Altman plots and paired t-test. The measurements were populated within the limits
      of agreement. No statistically significant difference (p-values from paired t
      test for end-diastolic diameter, distension, stiffness index, arterial compliance
      were 0.36, 0.24, 0.47 and 0.11 respectively) was seen for the brachial artery
      measurements performed by the two operators. The correlation between the
      measurement made by the operators was highly significant (r=0.86, p-value=0.003).

PMID- 29059861
TI  - Modeling young and adult patients with cirrhosis through a three element
      windkessel (WK3e).
AB  - INTRODUCTION: Measurement of hemodynamic parameters constitutes an important tool
      in the management of patients with cirrhosis. In recent years, non-invasive
      measurements have gain attention, due to the potential complications associated
      to invasive procedures. OBJECTIVE: To characterize the hemodynamic alterations of
      cirrhosis in young and adult subjects, through a three element windkessel (WK3e).
      METHODS: Individuals were divided in three age groups: Young Healthy group
      (control, CG), Young Cirrhotic Group (YCG) and Adult Cirrhotic Group (ACG). A
      Finapres(r) Nova device was used to obtain cardiac output (CO), heart rate and
      arterial blood pressure. Systemic arterial compliance (C), peripheral resistance
      (R) and characteristic impedance (Zc) were also provided. Effective arterial
      elastance (Ea), left ventricular work (LVW), input impedance, efficiency and
      model cutoff frequency (WKCF) were assessed based on the provided data. RESULTS:
      CO resulted to be higher in ACG than in CG and YGC. LVW, C and WKcf showed an
      increase, while R and Ea showed a decrease. However, this behavior was not
      observed in YCG. CONCLUSION: Cirrhosis was properly modeled in young and adult
      subjects in terms of non-invasive measurements and a WK3e.

PMID- 29059862
TI  - SVM classifier on chip for melanoma detection.
AB  - Support Vector Machine (SVM) is a common classifier used for efficient
      classification with high accuracy. SVM shows high accuracy for classifying
      melanoma (skin cancer) clinical images within computer-aided diagnosis systems
      used by skin cancer specialists to detect melanoma early and save lives. We aim
      to develop a medical low-cost handheld device that runs a real-time embedded SVM
      based diagnosis system for use in primary care for early detection of melanoma.
      In this paper, an optimized SVM classifier is implemented onto a recent FPGA
      platform using the latest design methodology to be embedded into the proposed
      device for realizing online efficient melanoma detection on a single system on
      chip/device. The hardware implementation results demonstrate a high
      classification accuracy of 97.9% and a significant acceleration factor of 26 from
      equivalent software implementation on an embedded processor, with 34% of
      resources utilization and 2 watts for power consumption. Consequently, the
      implemented system meets crucial embedded systems constraints of high performance
      and low cost, resources utilization and power consumption, while achieving high
      classification accuracy.

PMID- 29059863
TI  - Developing interactive and simple electromyogram PONG game for foot dorsiflexion
      and plantarflexion rehabilitation exercise.
AB  - Gaming systems have been proven to be able to improve physical and cognitive
      skills. Several studies have integrated games to be part of rehabilitation
      program to improve functional ability of human limbs in performing activities of
      daily living. This paper presents the development of an interactive
      electromyogram (EMG) based PONG game for foot dorsifexion and plantarflexion
      exercise. PONG game is selected because it is a classical game that can be easily
      comprehended and can be played by young and old people. Two surface EMG sensors
      were used in this work to acquire muscle activity of tibialis anterior muscle and
      gastrocnemius muscle. An experimental study was carried out to examine the
      viability of this sensor as input to play the game. The results were
      satisfactory. This study further strengthens the viability of using muscle
      activity as an input for gaming system and as a mean to monitor patient
      rehabilitation progress.

PMID- 29059864
TI  - Automatic detection and labeling of self-stimulatory behavioral patterns in
      children with Autism Spectrum Disorder.
AB  - An infrastructure to record, detect and label the behavioral patterns of children
      with Autism Spectrum Disorder (ASD) has been developed. The system incorporates 2
      different sensor platforms which are wearable and static. The wearable system is
      based on accelerometer which detects behavioral patterns of a subject, while the
      static sensors are microphones and cameras which captures the sounds, images and
      videos of the subjects within a room. The video also provides ground truth for
      wearable sensor data analysis. The system labels the segment of video data upon
      detection of the autistic behavior. That is, it stores the time of the video when
      the activities are detected. Time-Frequency methods are used to extract features
      and Hidden Markov Model (HMM) are used for analyzing the accelerometer signal.
      Using these methods, we are able to achieve 91.5% of classification rate for
      behavioral patterns studied in this paper which is used to label and save data.

PMID- 29059865
TI  - Design of focal brain cooling system for suppressing epileptic seizures.
AB  - Epilepsy is a group of diseases caused by excessive neuronal activities, and one
      quarter of the patients do not become seizure-free by the existing treatments.
      The potential treatments include focal brain cooling, which aims to cool the
      region where the excessive neuronal activities begin. We are developing a focal
      brain cooling system. The system delivers cold saline to a cranially implanted
      cooling device. The outflow is cooled by a Peltier device and pumped for
      circulation. The Peltier device and the pump are activated only when a seizure is
      predicted. In this research, the length of time for cooling the brain was
      calculated with a computational fluid dynamics (CFD)-based model of the focal
      brain cooling system. As a result, it takes less than 10 minutes for the average
      temperature 2 mm below the cooling device to reach 25.0  degrees C. It is much
      shorter than the time from seizure prediction to seizure onset when an existing
      algorithm for prediction is used.

PMID- 29059866
TI  - Smartphone app to investigate the relationship between social connectivity and
      mental health.
AB  - Interpersonal relationships are necessary for successful daily functioning and
      wellbeing. Numerous studies have demonstrated the importance of social
      connectivity for mental health, both through direct peer-to-peer influence and by
      the location of individuals within their social network. Passive monitoring using
      smartphones provides an advanced tool to map social networks based on the
      proximity between individuals. This study investigates the feasibility of using a
      smartphone app to measure and assess the relationship between social network
      metrics and mental health. The app collected Bluetooth and mental health data in
      63 participants. Social networks of proximity were estimated from Bluetooth data
      and 95% of the edges were scanned at least every 30 minutes. The majority of
      participants found this method of data collection acceptable and reported that
      they would be likely to participate in future studies using this app. These
      findings demonstrate the feasibility of using a smartphone app that participants
      can install on their own phone to investigate the relationship between social
      connectivity and mental health.

PMID- 29059867
TI  - Spatial targeting of tumor-associated macrophage and tumor cells with a designer
      nanocarrier for cancer chemo-immunotherapy.
AB  - Chemo-immunotherapy which combines chemotherapeutics with immune-modulating
      agents represents an appealing approach to improving cancer therapy [1, 2]. To
      maximize its efficacy, differential and precise targeting of the multiple
      therapeutics into corresponding cells is desirable. Here we develop an
      immunostimulatory nanocarrier that simultaneously loads platinum (Pt)-based
      chemotherapeutic prodrug and BLZ-945, a small molecule inhibitor of colony
      stimulating factor 1 receptor (CSF-1R) of tumor-associated macrophages (TAMs)
      [3], to spatially target tumor cells and TAMs for cancer chemo-immunotherapy. The
      nanoparticles (denoted as BLZ-945SCNs/Pt) undergo supersensitive structure
      collapse through responding to tumor acidity, along with instantaneous release of
      BLZ-945 and Pt-prodrug conjugated small particles. The extracellularly released
      BLZ-945 could be taken up by TAMs, which locate preferentially in the
      perivascular region [4], to directly disturb CSF-1/CSF-1R signaling pathway to
      suppress TAMs and modulate the tumor immune microenvironment, while the released
      small particles carrying Pt-prodrug could penetrate deeply into bulk tumor to
      kill more cancer cells [5], realizing synergistic antitumor effect of chemo- and
      immunotherapy (Fig. 1). Our in vivo studies demonstrate that the co-delivery
      nanocarrier outperforms monotherapy in varying tumor models.

PMID- 29059868
TI  - Needle-free small-volume liquid injection system powered by a rotary actuator.
AB  - Controllable jet injection could provide a fast, repeatable method for delivery
      of small volume, high viscosity drugs to the dermis. We have developed a compact,
      lightweight jet injector that uses a small commercial rotary motor and
      differential screw to create a jet of fluid with sufficient force to deliver drug
      into tissue. Clear tissue analogue and ex vivo tissue were used to demonstrate
      repeatable delivery of <;10 MUL of fluid using the device. The fluid when forced
      through a narrow orifice (108 MUm) reaches a velocity of >250 m/s with an
      injection time of <;3 ms.

PMID- 29059869
TI  - High-speed X-ray analysis of liquid delivery during jet injection.
AB  - The effect of varying velocity during jet injection on the dispersion of fluid
      into tissue is investigated using a custom-built X-ray imaging system. Injections
      are performed into ex-vivo porcine abdominal tissue using a voice coil actuated
      injection device. Single velocity and two-phase velocity injections reveal the
      complex nature of the dispersion of the fluid jet in layered tissue and highlight
      the effects of changing the jet velocity following the initial penetration of the
      liquid into the tissue.

PMID- 29059870
TI  - Nonlithographic fabrication of inflatable and deflatable polydimethylsiloxane
      (PDMS) micro-channels for magnetic actuation.
AB  - An implantable drug delivery device with an inflatable/deflatable reservoir, a
      release rate controlling micro-channel, a syringe attachable inlet, a
      unidirectional channel preventing drug substances from flowing back into the
      inlet, and a magnetic polydimethylsiloxane (PDMS) outlet capable of on-demand
      drug release was designed and fabricated to realize effective drug therapy. The
      reservoir is refillable through the inlet. Therefore, the device is reusable. The
      device does not employ photolithography patterning. Vapor coating, a precise
      cutting plotter, a vinyl adhesive material, and oxygen plasma treatment were
      employed to fabricate the device. Drug release rate was controlled by the micro
      channel attached to the reservoir. Micro-channels with widths 300MUm, 400MUm,
      500MUm and depth 95MUm were tested. Drug release is executed by deflecting the
      magnetic membrane outlet by an external electromagnetic field generating source:
      a permanent magnet or a planar copper coil.

PMID- 29059871
TI  - Ampoule and nozzle development for needle-free injections.
AB  - A rigid, compact, multi-piece ampoule has been designed and fabricated as a
      platform to conveniently house different nozzle inserts one at a time to offer
      increased jet consistency and functional flexibility. Three different nozzle
      geometries that respectively produce a single axial jet, radial jets, and
      intersecting jets are designed and fabricated. Through high-speed imaging and
      injection into tissue analog and ex vivo porcine tissue, these nozzles are
      demonstrated to have potential for a range of injection applications including
      intradermal, intratympanic, and traditional uses. The presented ampoule is more
      successful than a commercial jet injection ampoule in adhering to desired
      position and velocity trajectories and the energy efficiencies of jet ejections
      are compared.

PMID- 29059873
TI  - Rodent brain extraction using B-spline based deformable model.
AB  - Accurate rodent brain extraction is one of the basic steps for many translational
      study using Magnetic Resonance Imaging (MRI). In this paper, we present a new
      approach to model the rodent brain variation using non-rigid B-spline image
      registration for the brain extraction in MRI images. We model the shape and
      appearance with the B-spline parameters together with a mean brain image.
      Followed by a method using multi-expert, we refine the brain extraction region.
      Compared with the image-based template model using cross-correlation, the
      performance for rodent brain extraction has shown much improvement on one data
      set while maintaining the similar yet more consistent performance for another.
      Both template based methods however outperform the voxel based method (3D PCNN)
      and a modified BET version for rodent brain extraction.

PMID- 29059872
TI  - Nanoparticle-based delivery of an anti-proliferative metal chelator to tumor
      cells.
AB  - This paper describes the preparation and characterization of polymeric
      nanoparticles loaded with a potent anti-tumor metal chelator, Di-2-pyridylketone
      4,4-dimethyl-3-thiosemicarbazone (Dp44mT) for delivery to cancer cells. Metal
      chelators have been increasingly studied for their anti-cancer properties that
      rely on the high demand of neoplastic cells for iron. Dp44mT has previously shown
      great antiproliferative characteristics in several cancers including breast
      cancer and melanoma. To further expand the application of this highly cytotoxic
      agent for cancer treatment and to enable its specific delivery to malignant
      cells, here we apply nano-scale particles (NPs) of biodegradable poly(lactic-co
      glycolide) (PLGA) for encapsulation of Dp44mT and evaluate its effectiveness in
      vitro. The results demonstrated that Dp44mT was efficiently encapsulated in PLGA
      particles. Resulting NPs were uniform in size and shape and had good colloidal
      stability. Moreover, Dp44mT encapsulation in PLGA enhanced the water solubility
      of this agent. Lastly, the present formulation showed high level of cytotoxicity
      in glioma cells. Together, these results show the potential of PLGA NPs as a nano
      carrier for Dp44mT with no apparent impact on the anti-tumor activity of this
      compound.

PMID- 29059874
TI  - Individual muscle segmentation in MR images: A 3D propagation through 2D non
      linear registration approaches.
AB  - Manual and automated segmentation of individual muscles in magnetic resonance
      images have been recognized as challenging given the high variability of shapes
      between muscles and subjects and the discontinuity or lack of visible boundaries
      between muscles. In the present study, we proposed an original algorithm allowing
      a semi-automatic transversal propagation of manually-drawn masks. Our strategy
      was based on several ascending and descending non-linear registration approaches
      which is similar to the estimation of a Lagrangian trajectory applied to manual
      masks. Using several manually-segmented slices, we have evaluated our algorithm
      on the four muscles of the quadriceps femoris group. We mainly showed that our 3D
      propagated segmentation was very accurate with an averaged Dice similarity
      coefficient value higher than 0.91 for the minimal manual input of only two
      manually-segmented slices.

PMID- 29059875
TI  - A novel non-rigid registration algorithm for zebrafish larval images.
AB  - Precise three-dimensional mapping of a large number of gene expression patterns,
      neuronal types and connections to an anatomical reference helps us to understand
      the vertebrate brain and its development. Zebrafish has evolved as a model
      organism for such study. In this paper, we propose a novel non-rigid registration
      algorithm for volumetric zebrafish larval image datasets. A coarse affine
      registration using the L-BFGS algorithm is applied first on the moving dataset.
      We then divide this coarsely registered moving image and the reference image into
      a union of overlapping patches. Minimum weight bipartite graph matching algorithm
      is employed to find the correspondence between the two sets of patches. The
      corresponding patches are then registered using the diffeomorphic demons method
      with proper intra-patch regularization. For each voxel lying in the overlapping
      regions, we impose inter-patch regularization through a composite transformation
      obtained from the adjacent transformation fields. Experimental results on four
      multi-view confocal 3D datasets show the advantage of the proposed solution over
      the existing ViBE-Z software.

PMID- 29059876
TI  - Parallel implementation of a nonrigid image registration algorithm for lung tumor
      boundary tracking in quasi real-time MRI.
AB  - This study presents an accelerated implementation of a two-dimensional moving
      mesh point correspondence algorithm using a GPU for tracking mobile tumor
      boundaries during radiation therapy. Normal CPU implementation of this algorithm
      is computationally intensive and time-consuming which limits its clinical
      utility, hence the need for a faster GPU implementation. One of the
      computationally intensive parts of the registration algorithm involves
      numerically solving a partial differential equation. In this paper we demonstrate
      that the computational performance of the algorithms can be improved by utilizing
      a shared memory implementation on the GPU. Evaluations in comparison to 600
      manually drawn contours showed that the proposed GPU-based tracking of the tumor
      boundaries yielded similar level of accuracy as the CPU based approach with
      improved computational efficiency.

PMID- 29059877
TI  - Characterization of single cell dynamic morphology by local deformation pattern
      modeling.
AB  - Computational analysis of cell dynamic morphology in time-lapse images has become
      a new topic of biomedical research. For single cell, it is a challenging task to
      consider the spatial inconsistency and the temporal accumulation of cell
      deformation. This paper introduces an innovative automate analysis method, in
      which temporal features of contour point deformation are captured and then local
      deformation pattern is modeled to characterize cell dynamic morphology and
      predict cell activation statue. We applied the method to classify lymphocyte
      videos of multiple groups. Experimental results demonstrate that the proposed
      method overcomes existing methods in accuracy and robustness.

PMID- 29059878
TI  - A statistical shape model of the skull developed from a South African population.
AB  - This paper discusses the development of a statistical shape model (SSM) of the
      skull from a South African population. A total of 16 skulls is used together with
      a reference from the Basel Face Model. A free-form deformation model is built
      using the reference model and the squared exponential kernel. The freeform model
      is used to establish dense correspondence across the skull sample and the in
      correspondence skulls are then used to build an SSM. The validity of the SSM is
      assessed using leave-one-out cross-validation with its generality ranging between
      1.47 mm and 1.84 mm and, the specificity ranging between 1.74 mm and 2.11 mm.

PMID- 29059879
TI  - Investigating the effect of cardiac oscillations and deadspace gas mixing during
      apnea using computer simulation.
AB  - Gaseous mixing in the anatomical deadspace with stimulation of respiratory
      ventilation through cardiogenic oscillations is an important physiological
      mechanism at the onset of apnea, which has been credited with various beneficial
      effects, e.g. reduction of hypercapnia during the use of low flow ventilation
      techniques. In this paper, a novel method is proposed to investigate the effect
      of these mechanisms in silico. An existing computational model of cardio
      pulmonary physiology is extended to include the apneic state, gas mixing within
      the anatomical deadspace, insufflation into the trachea and cardiogenic
      oscillations. The new model is validated against data published in an
      experimental animal (dog) study that reported an increase in arterial partial
      pressure of carbon dioxide (PaCO2) during apnea. Computational simulations
      confirm that the model outputs accurately reproduce the available experimental
      data. This new model can be used to investigate the physiological mechanisms
      underlying clearance of carbon dioxide during apnea, and hence to develop more
      effective ventilation strategies for apneic patients.

PMID- 29059880
TI  - Evaluation of indirect measures of neural inspiratory time from invasive and
      noninvasive recordings of respiratory activity.
AB  - Measuring diaphragmatic electromyography (EMGdi) provides an indirect
      quantification of neural respiratory drive and allows the delimitation of
      diaphragm neural activation and deactivation during inspiration. EMGdi recordings
      have been incorporated in novel modes of assisted mechanical ventilation, such as
      neurally adjusted ventilatory assist (NAVA), to trigger and cycle-off the
      ventilator. The EMGdi signal improves the assistance delivered by more
      conventional ventilatory modes, in which the ventilator is synchronized with the
      patient employing a pneumatic triggering. In this work, we evaluate the time
      delay between the onset and offset of inspiratory activity estimated from EMGdi
      and three respiratory mechanical signals: the respiratory flow (FL), the
      transdiaphragmatic pressure (Pdi) and the diaphragm length (Ldi) signals. To this
      purpose, these signals were acquired in three mongrel dogs surgically
      instrumented under general anesthesia. Onsets and offsets were estimated manually
      and by automatic algorithms on these signals. The highest delays were obtained
      between EMGdi and FL (100 ms) while the lowest delays were obtained between EMGdi
      and Pdi (8 ms). Moreover, differences between manual and automatic estimations
      showed a mean absolute error lower than 45 ms. In conclusion, our study points
      out that both EMGdi and Pdi signals detect the onset and offset of inspiratory
      activity earlier than the FL signal, and would therefore be better for the
      improvement of patient-ventilator synchrony.

PMID- 29059881
TI  - Statistical analysis of the age dependence of the normal capnogram.
AB  - The age dependence of the time-based capnogram from normal, healthy subjects has
      not been quantitatively characterized. The existence of age dependence would
      impact the development and operation of automated quantitative capnographic
      tools. Here, we quantitatively assess the relationship between normal capnogram
      shape and age. Capnograms were collected from healthy subjects, and
      physiologically-based features (exhalation duration, end-tidal CO2 and time spent
      at this value, normalized time spent at end-tidal CO2, end-exhalation slope, and
      instantaneous respiratory rate) were computationally extracted. The mean values
      of the individual features over 30 exhalations were linearly regressed against
      subject age, accounting for inter-feature correlation. After data collection, 154
      of 178 subjects were eligible for analysis, with an age range of 3-78 years (mean
      age 39, std. dev. 20 years). The Bonferroni-corrected joint 95% confidence
      intervals (CIs) of the regression line slopes contained the origin for five of
      six features (the remaining CI was only slightly offset from the origin). The
      associated individual r2 values for the regressions were all below 0.07. We
      conclude that age is not a significant explanatory factor in describing
      variations in the shape of the normal capnogram. This finding could be exploited
      in the design of automated methods for quantitative capnogram analysis across a
      range of ages.

PMID- 29059882
TI  - Imaging of regional air distributions in porcine lungs using high-performance
      electrical impedance tomography system.
AB  - Electrical impedance tomography (EIT) allows functional imaging of regional lung
      ventilation for real-time bedside monitoring of mechanically ventilated patients.
      Images showing time-changes of regional air distributions in the lungs can
      provide valuable diagnostic information for lung protective mechanical
      ventilation. This paper reports in vivo porcine imaging experiments of regional
      lung ventilation using a 16-channel parallel EIT system. Real-time time
      difference chest images of 10 animals were reconstructed during mechanical
      ventilations with a temporal resolution of 50 frame/s. Analyzing the images
      together with the airway volume-pressure information from the mechanical
      ventilator, we could successfully produce regional compliance images at PEEP
      (positive end expiratory pressure) titration. From in vivo animal experiments, we
      propose the method as a continuous monitoring means for LPV (lung protective
      ventilation).

PMID- 29059883
TI  - Monitoring of cardiac output and lung ventilation by Electrical Impedance
      Tomography in a porcine model of acute lung injury.
AB  - Adequate medical treatment of the Acute Respiratory Distress Syndrome is still
      challenging since patient-individual aspects have to be taken into account. Lung
      protective ventilation and hemodynamic stability have always been two of the most
      crucial aims of intensive care therapy. For both aspects, a continuous -
      preferably non-invasive - monitoring is desirable that is available at the
      bedside. Unfortunately, there is no technique clinically established yet, that
      provides both measurement of cardiac stroke volume and ventilation dynamics in
      real-time. Electrical Impedance Tomography (EIT) is a promising technique to
      close this gap. The aim of the study was to investigate if stroke volume can be
      estimated by a self-developed software using EIT-based image analysis. In
      addition, two EIT-derived parameters, namely Global Inhomogeneity Index (GII) and
      Impedance Ratio (IR), were calculated to evaluate homogeneity of air
      distribution. Experimental acute lung injury (ALI) was provoked in seven female
      pigs (German Landrace) by lipopolysaccharide (LPS). All animals suffered from
      experimental ALI 3 to 4 hours after LPS infusion. At defined time points,
      respiratory and hemodynamic parameters, blood gas analyses and EIT-recordings
      were performed. Eight hours after ALI, animals were euthanized. Stroke volume,
      derived from pulmonary artery catheter (PAC), decreased continuously up to four
      hours after ALI. Then, stroke volume increased slightly. Stroke volume, derived
      from the self-developed tool, showed the same characteristics (p=0.047, r =
      0.365). In addition to the GII and IR individually, both classified scores showed
      a high correlation with the Horowitz Index, defined as paO2/FiO2. To conclude,
      EIT-derived measures enabled a reliable estimation of cardiac stroke volume and
      regional distribution of ventilation.

PMID- 29059884
TI  - A novel method for segmentation of Infrared Scanning Laser Ophthalmoscope (IR
      SLO) images of retina.
AB  - Retinal vessel segmentation forms an essential element of automatic retinal
      disease screening systems. The development of multimodal imaging system with IR
      SLO and OCT could help in studying the early stages of retinal disease. The
      advantages of IR-SLO to examine the alterations in the structure of retina and
      direct correlation with OCT can be useful for assessment of various diseases.
      This paper presents an automatic method for segmentation of IR-SLO fundus images
      based on the combination of morphological filters and image enhancement
      techniques. As a first step, the retinal vessels are contrasted using
      morphological filters followed by background exclusion using Contrast Limited
      Adaptive Histogram Equalization (CLAHE) and Bilateral filtering. The final
      segmentation is obtained by using Isodata technique. Our approach was tested on a
      set of 26 IR-SLO images and results were compared to two set of gold standard
      images. The performance of the proposed method was evaluated in terms of
      sensitivity, specificity and accuracy. The system has an average accuracy of 0.90
      for both the sets.

PMID- 29059885
TI  - A fluid-dynamic based approach to reconnect the retinal vessels in fundus
      photography.
AB  - This paper introduces the use of fluid-dynamic modeling to determine the
      connectivity of overlapping venous and arterial vessels in fundus images.
      Analysis of the retinal vascular network may provide information related to
      systemic and local disorders. However, the automated identification of the
      vascular trees in retinal images is a challenging task due to the low signal-to
      noise ratio, nonuniform illumination and the fact that fundus photography is a
      projection on to the imaging plane of three-dimensional retinal tissue. A zero
      dimensional model was created to estimate the hemodynamic status of candidate
      tree configurations. Simulated annealing was used to search for an optimal
      configuration. Experimental results indicate that simulated annealing was very
      efficient on test cases that range from small to medium size networks, while
      ineffective on large networks. Although for large networks the nonconvexity of
      the cost function and the large solution space made searching for the optimal
      solution difficult, the accuracy (average success rate = 98.35%), and simplicity
      of our novel approach demonstrate its potential effectiveness in segmenting
      retinal vascular trees.

PMID- 29059886
TI  - Vessel extraction in retinal images using automatic thresholding and Gabor
      Wavelet.
AB  - Retinal image analysis has been widely used for early detection and diagnosis of
      multiple systemic diseases. Accurate vessel extraction in retinal image is a
      crucial step towards a fully automated diagnosis system. This work affords an
      efficient unsupervised method for extracting blood vessels from retinal images by
      combining existing Gabor Wavelet (GW) method with automatic thresholding. Green
      channel image is extracted from color retinal image and used to produce Gabor
      feature image using GW. Both green channel image and Gabor feature image undergo
      vessel-enhancement step in order to highlight blood vessels. Next, the two vessel
      enhanced images are transformed to binary images using automatic thresholding
      before combined to produce the final vessel output. Combining the images results
      in significant improvement of blood vessel extraction performance compared to
      using individual image. Effectiveness of the proposed method was proven via
      comparative analysis with existing methods validated using publicly available
      database, DRIVE.

PMID- 29059887
TI  - A new two-dimensional matched filter based on the modified Chebyshev type I
      function for retinal vessels detection.
AB  - Retinal vessel segmentation takes a significant part in an automated diabetic
      retinopathy screening task. However, this can be a challenging job because of the
      low contrast retinal images and the presences of retinal pathologies. Hence, in
      this paper, we propose a novel matched filter based on the modified Chebyshev
      type I function for retinal blood vessels candidates detection. The proposed
      method is combined with the pre-processing and the post-processing phases to have
      a complete retinal vessel segmentation scheme. The retinal images from the DRIVE
      and STARE databases, which are equipped with the ground truths are used to
      evaluate our proposed method in the segmentation scheme. Using our method, the
      achieved average levels of sensitivity, specificity, and accuracy are 0.756,
      0.973, and 0.954, for the DRIVE database, and 0.731, 0.972, and 0.953, for the
      STARE database, being better than other presented methods. The high results
      indicate that our method is reliable to be used in an automated detection tool
      for diabetic retinopathy.

PMID- 29059888
TI  - Retinal biometrics based on Iterative Closest Point algorithm.
AB  - The pattern of blood vessels in the eye is unique to each person because it
      rarely changes over time. Therefore, it is well known that retinal blood vessels
      are useful for biometrics. This paper describes a biometrics method using the
      Jaccard similarity coefficient (JSC) based on blood vessel regions in retinal
      image pairs. The retinal image pairs were rough matched by the center of their
      optic discs. Moreover, the image pairs were aligned using the Iterative Closest
      Point algorithm based on detailed blood vessel skeletons. For registration,
      perspective transform was applied to the retinal images. Finally, the pairs were
      classified as either correct or incorrect using the JSC of the blood vessel
      region in the image pairs. The proposed method was applied to temporal retinal
      images, which were obtained in 2009 (695 images) and 2013 (87 images). The 87
      images acquired in 2013 were all from persons already examined in 2009. The
      accuracy of the proposed method reached 100%.

PMID- 29059889
TI  - An experimental evaluation of the accuracy of keypoints-based retinal image
      registration.
AB  - This work regards an investigation of the accuracy of a state-of-the-art,
      keypoint-based retinal image registration approach, as to the type of keypoint
      features used to guide the registration process. The employed registration
      approach is a local method that incorporates the notion of a 3D retinal surface
      imaged from different viewpoints and has been shown, experimentally, to be more
      accurate than competing approaches. The correspondences obtained between SIFT,
      SURF, Harris-PIIFD and vessel bifurcations are studied, either individually or in
      combinations. The combination of SIFT features with vessel bifurcations was found
      to perform better than other combinations or any individual feature type, alone.
      The registration approach is also comparatively evaluated against representative
      methods of the state-of-the-art in retinal image registration, using a benchmark
      dataset that covers a broad range of cases regarding the overlap of the acquired
      images and the anatomical characteristics of the imaged retinas.

PMID- 29059890
TI  - Design of sEMG-detecting circuit for EMG-Bridge.
AB  - A surface electromyography (sEMG) signal typically results from the electrical
      activities of many muscle fibers, and can be utilized as a signal source in
      prostheses due to its abundance of movement information. This paper proposes an
      sEMG-detection circuit for the acquisition of the controlling signal in EMG
      Bridge (EMGB) systems. The detection circuit mainly comprises a preamplifier, a
      driven right leg (DRL) circuit, a high-pass filter (HPF), a low-pass filter
      (LPF), and a gain adjustable amplifying circuit. The common-mode rejection ratio
      (CMRR) of the circuit is higher than 120 dB, the input impedance is greater than
      100 MOmega, the passband range is 20~450 Hz, and the frequency attenuation in
      stopband is not less than 120dB/dec.

PMID- 29059891
TI  - The effect of the preparation instruction on the functional connectivity between
      forearm muscles during movement's initiation.
AB  - This study investigates the effect of preparation warning on the functional
      connectivity between forearm muscles during movement's initiation. The Normalized
      Mutual Information (NMI) is the used indicator. It is calculated for muscle pairs
      activated during a handgrip exercice. They are innervated by the same nerve or by
      different nerves. Results show that: i) NMI is more important when muscles pairs
      are stimulated by the same nerve during both preparation and motor activities.
      ii) NMI is higher during preparation comparing to motor activity. iii) The
      functional connectivity during contraction's beginning increases when a
      preparation warning is given. We conclude that muscles put together their effort
      to initiate the movement especially when participants prepare in advance their
      activity.

PMID- 29059892
TI  - sEMG feature selection and classification using SVM-RFE.
AB  - It is challenging to obtain good results for hand movements classification.
      Previous studies expended efforts on filters for sEMG data, feature extraction
      and classifier algorithms to achieve the best results. This paper proposes the
      insertion of a step in the classification process that selects which features to
      use in training aiming to increase accuracy and performance. Feature selection
      was previously used in other classification tasks but is new in wrist/fingers
      movements classification. Obtained results were positives as the performance gain
      is huge (39 to 53 features out of 144 are used for classification) and accuracy
      reach promising values (above 90% for some subjects).

PMID- 29059893
TI  - EMG-based energy expenditure optimization for active prosthetic leg tuning.
AB  - In recent years, active prosthetic legs have been developed and deployed
      commercially that help amputees to initiate gait with less effort and more
      symmetry in the pattern. However, the process of initial set up and tuning is
      highly time and cost consuming. It requires prosthetic experts to observe the
      gait and the feedback from amputees to manually tune the parameters subjectively.
      In this study, an electromyography (EMG)-based energy expenditure optimization
      method was presented to automatically tune the prosthetic limb. For this purpose,
      a wide variety of lower body muscles were observed and the energy expenditure was
      modeled based on their electrical activity. The tuning optimization was
      implemented based on a grid-searching protocol designed in this study. This
      method resulted in a power value comparable to manual tuning, which provided
      enough force to facilitate gait for amputees. This study shows the feasibility of
      automatic tuning and removal of the need for referral to an expert.

PMID- 29059894
TI  - Muscle fatigue assessment through electrodermal activity analysis during
      isometric contraction.
AB  - We studied the effects of muscle fatigue on the Autonomic Nervous System (ANS)
      dynamics. Specifically, we monitored the electrodermal activity (EDA) on 32
      healthy subjects performing isometric biceps contraction. As assessed by means of
      an electromyography (EMG) analysis, 15 subjects showed muscle fatigue and 17 did
      not. EDA signals were analyzed using the recently proposed cvxEDA model in order
      to decompose them into their phasic and tonic components and extract effective
      features to study ANS dynamics. A statistical comparison between the two groups
      of subjects was performed. Results revealed that relevant phasic EDA features
      significantly increased in the fatigued group. Moreover, a pattern recognition
      system was applied to the EDA dataset in order to automatically discriminate
      between fatigued and non-fatigued subjects. The proposed leave-one-subject-out
      KNN classifier showed an accuracy of 75.69%. These results suggest the use of EDA
      as correlate of muscle fatigue, providing integrative information to the standard
      indices extracted from the EMG signals.

PMID- 29059895
TI  - Consistency of surface electromyography assessment at lower limb selected muscles
      during vertical countermovement.
AB  - Given the difficulty of invasive methods to assess muscle action during natural
      human movement, surface electromyography (sEMG) has been increasingly used to
      capture muscle activity in relation to kinesiological analysis of specific tasks.
      Isolated isometric, concentric and eccentric forms of muscle action have been
      receiving the most attention for research purposes. Nevertheless natural muscle
      action frequently involves the use of a preceding eccentric muscle action as a
      form of potentiation of immediate muscle concentric action, in what is designated
      as muscle stretch-shortening cycle (SSC). The most frequently applied protocols
      for the evaluation of SSC on vertical jumps are by virtue of their
      reproducibility and control of experimental conditions, squat jump (SJ) without
      countermovement (CM), countermovement jump (CMJ) with long CM and drop jump (DJ)
      with short CM. The methods used to extract information and relationship of the
      captured signals also present a high diversity, with the question about the
      consistency of the methods and obtained results. The objective of this study is
      to evaluate the consistency of the analysis and results by applying different
      EMGs signal analysis techniques related to strategic muscle groups of the lower
      limbs at different countermovement evaluated in vertical jumps. Raw sEMG signals
      of 5 lower limb muscles of 6 subjects during SJ, CMJ and DJ were rectified,
      filtered and obtained their envelope, and then correlated (CR) for detection of
      synergistic, agonist and antagonist activity, applied principal component
      analysis (PCA) for the detection of uncorrelated components explaining maximum
      variability and normalized cross-correlation (CCRN) for detection of maximum
      correlations and time lag. CR of EMG envelopes presented higher coactivities
      (CoA) in DJ relative to SJ and these CoA superior to CMJ with greater synergy in
      DJ relative to SJ and CMJ that present several loop cycles corresponding to time
      lag of activity. CCRN of the EMG envelopes presented also higher CoA in DJ when
      compared to SJ and both higher CoA to CMJ. PCA allowed to detect a principal
      component (PC) explaining 92.2% of the variability of EMG in DJ, 90.6% in SJ and
      78.7% in CMJ, the second PC responsible for the explanation of 4.9% variability
      in DJ, 6.7% in SJ and 15.3% in CMJ.

PMID- 29059896
TI  - Increasing the robustness against force variation in EMG motion classification by
      common spatial patterns.
AB  - In the practical use of an electromyography (EMG) pattern-recognition based
      myoelectric prosthesis, the variation of force levels to do a motion would be
      inevitable, which will cause a change of EMG patterns. Therefore, the force
      variation will decay the performance of a trained classifier. In this study, the
      common spatial pattern (CSP) method was proposed with an attempt to improve the
      robustness of EMG-PR based classifier against force variation. The EMG signals
      were acquired from three able-bodied subjects when they were performing the
      motions at low, medium, and high force levels, respectively. And in the pattern
      recognition, CSP features were extracted from the EMG signals for motion
      classification. By comparing the classification accuracies between the CSP and
      the commonly used time-domain (TD) features, the CSP features showed a better
      robustness against force variation with an increment of 5.3% of the average
      classification accuracy. Especially, the classification accuracy of a classifier
      was 84.2% when tested at low force level by using CSP features, which was 18.5%
      higher than that of the TD features. These preliminary results suggest that using
      CSP features may increase the robustness of EMG-based myoelectric control.

PMID- 29059897
TI  - Capacitively coupled EMG detection via ultra-low-power microcontroller STFT.
AB  - As motion artefacts are a major problem with electromyography sensors, a new
      algorithm is developed to differentiate artefacts to contraction EMG. The
      performance of myoelectric prosthesis is increased with this algorithm. The
      implementation is done for an ultra-low-power microcontroller with limited
      calculation resources and memory. Short Time Fourier Transformation is used to
      enable real-time application. The sum of the differences (SOD) of the currently
      measured EMG to a reference contraction EMG is calculated. The SOD is a new
      parameter introduced for EMG classification. The satisfactory error rates are
      determined by measurements done with the capacitively coupling EMG prototype,
      recently developed by the research group.

PMID- 29059898
TI  - Personalized features for attention detection in children with Attention Deficit
      Hyperactivity Disorder.
AB  - Measuring attention from electroencephalogram (EEG) has found applications in the
      treatment of Attention Deficit Hyperactivity Disorder (ADHD). It is of great
      interest to understand what features in EEG are most representative of attention.
      Intensive research has been done in the past and it has been proven that
      frequency band powers and their ratios are effective features in detecting
      attention. However, there are still unanswered questions, like, what features in
      EEG are most discriminative between attentive and non-attentive states? Are these
      features common among all subjects or are they subject-specific and must be
      optimized for each subject? Using Mutual Information (MI) to perform subject
      specific feature selection on a large data set including 120 ADHD children, we
      found that besides theta beta ratio (TBR) which is commonly used in attention
      detection and neurofeedback, the relative beta power and theta/(alpha+beta)
      (TBAR) are also equally significant and informative for attention detection.
      Interestingly, we found that the relative theta power (which is also commonly
      used) may not have sufficient discriminative information itself (it is
      informative only for 3.26% of ADHD children). We have also demonstrated that
      although these features (relative beta power, TBR and TBAR) are the most
      important measures to detect attention on average, different subjects have
      different set of most discriminative features.

PMID- 29059899
TI  - Modular framework for detection of inter-ictal spikes in iEEG.
AB  - In this paper, we present a new modular approach for detection of inter-ictal
      spikes in intracranial iEEG recordings from patients that are suffering from
      pharmaco-resistant form of epilepsy. This new approach is presented in the form
      of a detection framework consisting of three primary modules: first level
      detector, second level feature extractor, and third level detection classifier,
      where each module is responsible for a specific functionality. This detection
      framework can be perceived as a three slot system, where modules can be easily
      plugged in their slots and replaced by a different module or implementation on
      demand, in order to adapt the quality of detection (measured in terms of
      sensitivity, precision or inter-recording adaptability) and computational cost.
      Using complex real-world data sets it was confirmed that the proposed framework
      provides highly sensitive and precise detection, while it also significantly
      reduces the computation time.

PMID- 29059900
TI  - Bispectral analysis of spontaneous EEG activity from patients with moderate
      dementia due to Alzheimer's disease.
AB  - Dementia due to Alzheimer's disease (AD) is a common disorder with a great impact
      on the patients' quality of life. The aim of this pilot study was to characterize
      spontaneous electroencephalography (EEG) activity in dementia due to AD using
      bispectral analysis. Five minutes of EEG activity were recorded from 17 patients
      with moderate dementia due to AD and 19 age-matched controls. Bispectrum results
      revealed that AD patients are characterized by an increase of phase coupling at
      low frequencies in comparison with controls. Additionally, some bispectral
      features calculated from the bispectrum showed significant differences between
      both groups (p <; 0.05, Mann-Whitney U test with Bonferroni's correction).
      Finally, a stepwise logistic regression analysis with a leave-one-out cross
      validation procedure was used for classification purposes. An accuracy of 86.11%
      (sensitivity = 88.24%; specificity =84.21%) was achieved. This study suggests the
      usefulness of bispectral analysis to provide further insights into the underlying
      brain dynamics associated with AD.

PMID- 29059901
TI  - A fully automated method for segmentation and classification of local field
      potential recordings. Preliminary results.
AB  - Identification of brain states measured with electrophysiological methods such as
      electroencephalography and local field potential (LFP) recordings is of great
      importance in numerous neuroscientific applications. For instance, in Brain
      Computer Interface, in the diagnosis of neurological disorders as well as to
      investigate how brain rhythms stem from synchronized physiological mechanisms
      (e.g., memory and learning). In this work, we propose a fully automated method
      with the aim of partitioning LFP signals into stationary segments as well as
      classifying each detected segment into three different classes (delta, regular
      theta or irregular theta rhythms). Our approach is computationally efficient
      since the process of detection and partition of signals into stationary segments
      is only based on two features (the variance and the so-called spectral error
      measure) and allow the classification at the same time. We developed the
      algorithm upon analyzing six anesthetized rats, resulting in a true positive rate
      of 97.5%, 91.8% and 79.1% in detecting delta, irregular theta and regular theta
      rhythms, respectively. This preliminary quantitative evaluation offers
      encouraging results for further research.

PMID- 29059902
TI  - On the impact of spike segmentation on motor unit identification in dynamic
      surface electromyograms.
AB  - We discuss the adaptation of preexisting Convolution Kernel Compensation (CKC)
      surface electromyogram (EMG) decomposition technique to dynamic muscle
      contractions. In particular, three different algorithms for segmentation of motor
      unit (MU) spike trains into MU firings are discussed and mutually compared on
      synthetic dynamic surface EMG. The first segmentation algorithm employs a priori
      knowledge of the regularity of MU firings. The second one builds on K-means
      classification of MU spikes, whereas the third one combines both the regularity
      of MU firings and the previously introduced Pulse-to-Noise Ratio (PNR). On
      average, 5.5 +/- 0.6 MUs were identified with sensitivity of 88.4 % +/- 17.0 %,
      83.8 % +/- 16.7 % and 90.7 % +/- 15.1 % for the first, the second and the third
      segmentation algorithm, respectively, demonstrating the feasibility of MU
      identification in moderate dynamic muscle contractions. In our tests, the third
      segmentation approach demonstrated superior accuracy in MU identification.

PMID- 29059903
TI  - Automated diagnosis of Coronary Artery Disease using pattern recognition
      approach.
AB  - Coronary Artery Disease (CAD) is the most leading Cardiovascular Disease (CVD),
      which results due to buildup of plaque inside the coronary arteries. The CAD and
      Normal Sinus Rhythm (NSR) heartbeats can be discriminated and diagnosed
      noninvasively using the standard tool Electrocardiogram (ECG). However, manual
      diagnosis of ECG is tiresome and time consuming task, due to complex nature and
      unseen nonlinearities of ECG. Hence an automated system plays a substantial role.
      In this study, CAD and NSR heartbeats are discriminated and diagnosed using
      Higher-Order Statistics (HOS) cumulants features. Further, the cumulants
      coefficients dimensionality reduced using Principal Components Analysis (PCA) and
      the medically significant features (p-value<;0.05) Principal Components (PCs) are
      subjected for classification using Random Forest (RAF) and Rotation Forest (ROF)
      ensemble classifiers. Proposed system is robust which helps in screening CAD risk
      factors and telemonitoring applications.

PMID- 29059904
TI  - Irregular heartbeat classification using Kronecker Product Equations.
AB  - Cardiac arrhythmia or irregular heartbeats are an important feature to assess the
      risk on sudden cardiac death and other cardiac disorders. Automatic
      classification of irregular heartbeats is therefore an important part of ECG
      analysis. We propose a tensor-based method for single- and multi-channel
      irregular heartbeat classification. The method tensorizes the ECG data matrix by
      segmenting each signal beat-by-beat and then stacking the result into a third
      order tensor with dimensions channel * time * heartbeat. We use the multilinear
      singular value decomposition to model the obtained tensor. Next, we formulate the
      classification task as the computation of a Kronecker Product Equation. We apply
      our method on the INCART dataset, illustrating promising results.

PMID- 29059905
TI  - Classification of respiratory disturbances in Rett Syndrome patients using
      Restricted Boltzmann Machine.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder that can cause
      pervasive wakeful respiratory disturbances that include tachypnea, breath
      holding, and central apnea. Quantitative analysis of these respiratory
      disturbances in RTT is considered a promising outcome measure for clinical
      trials. Currently, machine learning methodologies have not been employed to
      automate the classification of RTT respiratory disturbances. In this paper, we
      propose using temporal, flow, and autocorrelation features taken from the
      respiratory inductance plethsymography chest signal. We tested the performance of
      six classifiers including: Support Vector Machine, Restricted-Boltzmann-Machine,
      Back-propagation, Levenberg-Marquardt, and Decision-Fusion. We evaluate this
      classification in two modalities: (1) a subject-independent modality (leave-one
      subject-out) obtaining the best F1 score in 93.67%, and (2) a trial-independent
      modality (leave-one-trial-out per subject) obtaining the best F1 score in 78.21%.

PMID- 29059906
TI  - ECG authentication in post-exercise situation.
AB  - Human authentication based on electrocardiogram (ECG) has been a remarkable issue
      for recent ten years. This paper proposed an authentication technology with the
      ECG data recorded after the harsh exercise. 55 subjects voluntarily attended to
      this experiment. A stepper was used as an exercise equipment. The subjects are
      asked to do stepper for 5 minutes and their ECG signals are acquired before and
      after the exercise in rest, sitting posture. Linear discriminant analysis (LDA)
      was used for both feature extraction and classification. Even though, within the
      first 1 minute recording, the subject recognition accuracy was 59.64%, which is
      too low to utilize, after one minute the accuracy was higher than 90% and it
      increased up to 96.22% within 5 minutes, which is plausible to use in
      authentication circumstances. Therefore, we have concluded that ECG
      authentication techniques will be able to be used after 1 minute of catching
      breath.

PMID- 29059907
TI  - Bivariate empirical mode decomposition for ECG-based biometric identification
      with emotional data.
AB  - Emotions modulate ECG signals such that they might affect ECG-based biometric
      identification in real life application. It motivated in finding good feature
      extraction methods where the emotional state of the subjects has minimum impacts.
      This paper evaluates feature extraction based on bivariate empirical mode
      decomposition (BEMD) for biometric identification when emotion is considered.
      Using the ECG signal from the Mahnob-HCI database for affect recognition, the
      features were statistical distributions of dominant frequency after applying BEMD
      analysis to ECG signals. The achieved accuracy was 99.5% with high consistency
      using kNN classifier in 10-fold cross validation to identify 26 subjects when the
      emotional states of the subjects were ignored. When the emotional states of the
      subject were considered, the proposed method also delivered high accuracy, around
      99.4%. We concluded that the proposed method offers emotion-independent features
      for ECG-based biometric identification. The proposed method needs more evaluation
      related to testing with other classifier and variation in ECG signals, e.g.
      normal ECG vs. ECG with arrhythmias, ECG from various ages, and ECG from other
      affective databases.

PMID- 29059908
TI  - Cancelable ECG biometrics using GLRT and performance improvement using guided
      filter with irreversible guide signal.
AB  - Biometrics such as ECG provides a convenient and powerful security tool to verify
      or identify an individual. However, one important drawback of biometrics is that
      it is irrevocable. In other words, biometrics cannot be re-used practically once
      it is compromised. Cancelable biometrics has been investigated to overcome this
      drawback. In this paper, we propose a cancelable ECG biometrics by deriving a
      generalized likelihood ratio test (GLRT) detector from a composite hypothesis
      testing in randomly projected domain. Since it is common to observe performance
      degradation for cancelable biometrics, we also propose a guided filtering (GF)
      with irreversible guide signal that is a non-invertibly transformed signal of ECG
      authentication template. We evaluated our proposed method using ECG-ID database
      with 89 subjects. Conventional Euclidean detector with original ECG template
      yielded 93.9% PD1 (detection probability at 1% FAR) while Euclidean detector with
      10% compressed ECG (1/10 of the original data size) yielded 90.8% PD1. Our
      proposed GLRT detector with 10% compressed ECG yielded 91.4%, which is better
      than Euclidean with the same compressed ECG. GF with our proposed irreversible
      ECG template further improved the performance of our GLRT with 10% compressed ECG
      up to 94.3%, which is higher than Euclidean detector with original ECG. Lastly,
      we showed that our proposed cancelable ECG biometrics practically met cancelable
      biometrics criteria such as efficiency, re-usability, diversity and non
      invertibility.

PMID- 29059909
TI  - Similarity based hierarchical clustering of physiological parameters for the
      identification of health states - a feasibility study.
AB  - This paper introduces a new unsupervised method for the clustering of
      physiological data into health states based on their similarity. We propose an
      iterative hierarchical clustering approach that combines health states according
      to a similarity constraint to new arbitrary health states. We applied our method
      to experimental data in which the physical strain of subjects was systematically
      varied. We derived health states based on parameters extracted from ECG data. The
      occurrence of health states shows a high temporal correlation to the experimental
      phases of the physical exercise. We compared our method to other clustering
      algorithms and found a significantly higher accuracy with respect to the
      identification of health states.

PMID- 29059910
TI  - EEG emotion recognition using reduced channel wavelet entropy and average wavelet
      coefficient features with normal Mutual Information method.
AB  - Recognizing emotion from EEG signals is a complicated task that requires complex
      features and a substantial number of EEG channels. Simple algorithms to analyse
      the feature and reduce the EEG channel number will give an indispensable
      advantages. Therefore, this study explores a combination of wavelet entropy and
      average wavelet coefficient (WEAVE) as a potential EEG-emotion feature to
      classify valence and arousal emotions with the advantage of the ability to
      identify the occurrence of a pattern while at the same time identify the shape of
      a pattern in EEG emotion signal. The complexity of the feature was reduced using
      the Normalized Mutual Information (NMI) method to obtain a reduced number of
      channels. Classification with the WEAVE feature achieved 76.8% accuracy for
      valence and 74.3% for arousal emotion, respectively. The analysis with NMI shows
      that the WEAVE feature has linear characteristics and offers possibilities to
      reduce the EEG channels to a certain number. Further analysis also reveals that
      detection of valence emotion with reduced EEG channels has a different
      combination of EEG channels compared to arousal emotion.

PMID- 29059911
TI  - Fast spike detection in EEG using eigenvalue analysis and clustering of spatial
      amplitude distribution.
AB  - In the current study, we tested a proposed method for fast spike detection using
      a general-purpose computer. First, we performed eigenvalue analysis using a
      gradient calculated from two neighboring samples to detect high-amplitude
      negative peaks. Clustering was performed to classify detected peaks by
      considering amplitude distribution at scalp electrodes. Negative peaks were
      scored by considering electrodes in the detection process and the cluster to
      which each peak belonged. Spikes were detected using two parameters: score
      threshold, and the number of clusters. We then used precision and recall to
      eliminate overestimation of the performance of the method. The results revealed a
      tradeoff between precision and recall. Recall showed a maximum average value of
      0.90 in two subjects. In contrast, average precision was 0.21, and the false
      positive rate was almost four times higher than the true positive rate on the
      condition that 64 and 54 spikes were included in two subjects. Analysis of
      required processing time revealed that our method could complete spike detection
      in approximately one-eighth of the recording time.

PMID- 29059912
TI  - Rotational data augmentation for electroencephalographic data.
AB  - MOTIVATION: For deep learning on image data, a common approach is to augment the
      training data by artificial new images, using techniques like moving windows,
      scaling, affine distortions, and elastic deformations. In contrast to image data,
      electroencephalographic (EEG) data suffers even more from the lack of sufficient
      training data. METHODS: We suggest and evaluate rotational distortions similar to
      affine/rotational distortions of images to generate augmented data. RESULTS: Our
      approach increases the performance of signal processing chains for EEG-based
      brain-computer interfaces when rotating only around y- and z-axis with an angle
      around +/-18 degrees to generate new data. CONCLUSION: This shows that our
      processing efficient approach generates meaningful data and encourages to look
      for further new methods for EEG data augmentation.

PMID- 29059913
TI  - Surface and intracranial EEG spike detection based on discrete wavelet
      decomposition and random forest classification.
AB  - Epilepsy is a neurological disorder for which the electroencephalogram (EEG) is
      the most important diagnostic tool. In particular, this diagnosis heavily depends
      on the detection of interictal (between seizures) paroxysmal epileptic discharges
      (IPED) in the EEG. This is a time-consuming task requiring significant training
      and experience. Automatic detection of these EEG patterns would greatly assist
      visual inspections of human readers. We present a new method, which allows
      automatic detection of IPED based on discrete wavelet decomposition and a random
      forest classifier. The algorithm was trained and cross validated using 17
      subjects with scalp EEG and 10 subjects with intracranial EEG. The performance of
      this method reached 62% recall and 26% precision for surface EEG subjects and 63%
      recall and 53% precision for intracranial EEG subjects. Thus, the method hereby
      proposed has great potential for diagnosis support in clinical environments.

PMID- 29059914
TI  - Analysis of Electroencephalogram of patients with specific low back pain with the
      massage treatment.
AB  - Through the investigation of the difference of approximate entropy (ApEn) and
      Hilbert-Huang Transform Marginal spectrum entropy (HHTMSEn) of the
      Electroencephalogram (EEG) signals of specific low back pain (SLBP) patients
      before and after the massage, we wanted to reveal the impact of the massage in
      the brain, and provided the basis for the massage treatment of SLBP patients. We
      recruited twenty-six SLBP patients and collected their spontaneous EEG signals
      before and after the massage. Firstly, we analyzed the ApEn and HHTMSEn of
      fourteen channels before and after the massage, and results showed that values of
      ApEn and HHTMSEn after the massage were less than the values before the massage
      significantly. And then, we extracted delta, theta, alpha and beta rhythms of the
      EEG signal, and analyzed the ApEn and HHTMSEn of the four rhythms before and
      after the massage. The results showed that the ApEn values of delta and alpha
      rhythm after the massage were significantly less than the values before the
      massage, and the HHTMSEn values of beta rhythms were significantly less than the
      values before the massage. The results of this study suggested the complexity of
      EEG signals was reduced with the relief of the pain after the massage therapy,
      and the change of pain of the SLBP patients was closely related to the change of
      the rhythms of the brain in the massage therapy, and the ApEn and the HHTMSEn
      features could serve as a base for quantitative assessment of SLBP condition
      after the massage therapy.

PMID- 29059915
TI  - EEG-based auditory attention decoding using unprocessed binaural signals in
      reverberant and noisy conditions?
AB  - To decode auditory attention from single-trial EEG recordings in an acoustic
      scenario with two competing speakers, a least-squares method has been recently
      proposed. This method however requires the clean speech signals of both the
      attended and the unattended speaker to be available as reference signals. Since
      in practice only the binaural signals consisting of a reverberant mixture of both
      speakers and background noise are available, in this paper we explore the
      potential of using these (unprocessed) signals as reference signals for decoding
      auditory attention in different acoustic conditions (anechoic, reverberant,
      noisy, and reverberant-noisy). In addition, we investigate whether it is possible
      to use these signals instead of the clean attended speech signal for filter
      training. The experimental results show that using the unprocessed binaural
      signals for filter training and for decoding auditory attention is feasible with
      a relatively large decoding performance, although for most acoustic conditions
      the decoding performance is significantly lower than when using the clean speech
      signals.

PMID- 29059916
TI  - EEG-based emotion classification using innovative features and combined SVM and
      HMM classifier.
AB  - Emotion classification is one of the state-of-the-art topics in biomedical signal
      research, and yet a significant portion remains unknown. This paper offers a
      novel approach with a combined classifier to recognise human emotion states based
      on electroencephalogram (EEG) signal. The objective is to achieve high accuracy
      using the combined classifier designed, which categorises the extracted features
      calculated from time domain features and Discrete Wavelet Transform (DWT). Two
      innovative designs are involved in this project: a novel variable is established
      as a new feature and a combined SVM and HMM classifier is developed. The result
      shows that the joined features raise the accuracy by 5% on valence axis and 1.5%
      on arousal axis. The combined classifier can improve the accuracy by 3% comparing
      with SVM classifier. One of the important applications for high accuracy emotion
      classification system is offering a powerful tool for psychologists to diagnose
      emotion related mental diseases and the system developed in this project has the
      potential to serve such purpose.

PMID- 29059917
TI  - A radiomics evaluation of 2D and 3D MRI texture features to classify brain
      metastases from lung cancer and melanoma.
AB  - Brain metastases are occasionally detected before diagnosing their primary site
      of origin. In these cases, simple visual examination of medical images of the
      metastases is not enough to identify the primary cancer, so an extensive
      evaluation is needed. To avoid this procedure, a radiomics approach on magnetic
      resonance (MR) images of the metastatic lesions is proposed to classify two of
      the most frequent origins (lung cancer and melanoma). In this study, 50 T1
      weighted MR images of brain metastases from 30 patients were analyzed: 27 of lung
      cancer and 23 of melanoma origin. A total of 43 statistical texture features were
      extracted from the segmented lesions in 2D and 3D. Five predictive models were
      evaluated using a nested cross-validation scheme. The best classification results
      were achieved using 3D texture features for all the models, obtaining an average
      AUC > 0.9 in all cases and an AUC = 0.947 +/- 0.067 when using the best model
      (naive Bayes).

PMID- 29059919
TI  - Atlas based sparse logistic regression for Alzheimer's Disease classification.
AB  - Sparse methods are an effective way to alleviate the curse of dimensionality in
      neuroimaging applications. By imposing sparsity inducing regularization terms
      these methods are able to perform feature selection jointly with
      classification.They have been used for Alzheimer's Disease (AD) and Mild
      cognitive impairment (MCI) classification using different approaches such as
      Lasso, Group Lasso and treestructured Group Lasso. The Group Lasso approaches
      have relied mainly on grouping contiguous voxels, either spatially or temporally.
      In this paper we propose two grouping approaches where feature groups are more
      disease related. We propose that features are grouped according to anatomically
      defined regions of the brain, as provided by a labeled atlas, and in a hierarchy
      that joins corresponding regions in the left and right hemispheres, so as to take
      into account the bilateral symmetry which typically occurs in AD. We apply our
      methods to MRI images from the ADNI and compare their performance with that of
      other sparse methods developed for AD. Evaluation includes classification
      performance and the stability of the obtained feature weights when several runs
      of these algorithms are performed. The proposed methods attained better or equal
      performance but generated more stable feature weights.

PMID- 29059918
TI  - Investigating the BOLD spectral power of the intrinsic connectivity networks in
      fibromyalgia patients: A resting-state fMRI study.
AB  - Recent advances in multivariate statistical analysis of blood oxygen level
      dependent (BOLD) functional magnetic resonance imaging (fMRI) have provided novel
      insights into the network organization of the human brain. Here, we applied group
      independent component analysis, a well-established approach for detecting brain
      intrinsic connectivity networks, to examine the spontaneous BOLD fluctuations in
      patients with fibromyalgia and healthy controls before and after exposure to a
      stressor. The BOLD spectral power characteristics of component time courses were
      calculated using the fast Fourier transform (FFT) algorithm, and group comparison
      was performed at six frequency bins between 0 and 0.24 Hz at 0.04 Hz intervals.
      Relative to controls, patients with fibromyalgia displayed significant BOLD
      spectral power differences in the default-mode, salience, and subcortical
      networks at the baseline level (PBon ferroni-corrected <; 0.05). Multivariate
      analysis of covariance (MANCOVA) further revealed significant effects of the cold
      water temperature, and pain rating on the spectral power of the sensorimotor,
      salience, and prefrontal networks, while the diagnosis of fibromyalgia influenced
      the BOLD spectral power of the salience and subcortical networks (PFDR-corrected
      <; 0.05). Since the BOLD spectral power reflects the degree of fluctuations
      within a network, future studies of the correlation between BOLD spectral power
      and pain processing can cast additional light on the nature of the central
      nervous system dysfunction in patients with chronic pain syndromes.

PMID- 29059920
TI  - PEAR: PEriodic and ApeRiodic signal separation for fast FMRI.
AB  - Undersampling of functional MRI (fMRI) data leads to increased temporal
      resolution, as it allows shorter acquisition time per frame. High quality
      reconstruction of fMRI data from undersampled measurements requires proper
      modeling of the fMRI data. Recent publications suggest that the fMRI signal is a
      superposition of periodic and aperiodic signals. In this paper we develop an fMRI
      reconstruction approach based on this modeling. The fMRI data is assumed to be
      composed of two components: a component that holds a sum of periodic signals
      which is sparse in the temporal Fourier domain and an component that holds the
      remaining imaging information (consisting of the background and aperiodic
      signals) which has low rank. Data reconstruction is done by solving a constrained
      problem that enforces a fixed, moderate rank on one of the components, and a
      limited number of temporal frequencies on the other. Our approach is coined PEAR 
      PEriodic and ApeRiodic signal separation for fast fMRI. Experimental results are
      based on fMRI reconstruction using realistic timecourses. Evaluation was
      performed both quantitatively and visually versus ground truth. Results
      demonstrate PEAR's improvement in estimating the realistic timecourses versus
      state-of-the-art approaches at acceleration ratio of R=16.6.

PMID- 29059921
TI  - Cortical response of the projected-thumb tactile sensation under TENS by MEG.
AB  - The existence of projected finger territories (PFTs) near the stump provides an
      essential way to realize the tactile sensation of lost fingers by transcutaneous
      electrical nerve stimulation (TENS). After amputation, the somatosensory cortex
      corresponding to lost fingers might be invaded by other cortical areas due to
      cortical plasticity. However, it was seldom observed how the amputees could feel
      the projected or lost finger tactile sensation in the cerebral cortex under TENS.
      To answer this question, by using magnetoencephalography (MEG), we investigated
      the cortical response under TENS of the projected thumb territory and normal
      thumb with 2 Hz current pulses. One subject with long-term left forearm
      amputation was recruited. The temporal and spatial characteristics of the
      activated cortical magnetic signals were analyzed. The Equivalent Current Dipoles
      (ECDs) corresponding to the strongest strength were mapped in the cerebral
      cortex, and the current density distribution were clearly illustrated. We found
      that the latencies at the maximum ECD strength were 60 +/- 1.41 ms for the
      projected thumb and 46 +/- 1.25 ms for the normal counterpart. The strongest ECD
      corresponding to projected thumb was located in the central sulcus near the
      mirror location of the normal thumb counterpart. And the response strengths of
      projected thumb cortex were stronger than normal thumb counterpart.

PMID- 29059922
TI  - Precise localization of silicone-based intercranial planar electrodes in magnetic
      resonance imaging.
AB  - Intercranial planar electrodes enable neural recordings with high spatial
      resolution in diagnosis as well as for treatments. The value of the measurements
      increases with the precision of localization of the electrodes related to the
      individual anatomy. In this context, post-implantation MRI provides excellent
      soft tissue contrast, but the accurate localization of electrodes is impaired by
      magnetic susceptibility artifacts. We have addressed this problem without adding
      a substantial burden to the electrode fabrication process. Simple silicone
      reference structures were strategically placed on the implant surface to
      visualize the electrodes position in MRI. These reference structures allowed high
      precision electrode localization independently of electrode imaging artifacts.
      This implant manufacturing approach could prove extremely useful in combination
      with existing image processing pipelines.

PMID- 29059923
TI  - A study of feature extraction for Alzheimer's disease based on resting-state
      fMRI.
AB  - The Alzheimer's Disease (AD) has become a major threat of human health with its
      incidence rate ascending year by year. Early diagnosis of AD is very important
      for AD patients to keep life quality. The resting-state fMRI (rs-fMRI) which
      precisely reflects the brain changes on the resting state of individuals provides
      a quantitative approach, which has been introduced to distinguish AD patients
      from normal population. In this study, we proposed a method to find the most
      distinctive features identifying AD patients from rs-fMRI images. The ALFF and
      ReHo parameters based on pre-processed rs-fMRI data were extracted, and some key
      parameters of the brain functional network based on graph theory were calculated.
      Then we tested the recognition performance of different classifiers, and the best
      classification algorithm, that is, Support Vector Machine (SVM) with linear
      kernel are selected. Finally through a recursive feature selection procedure, we
      got the most distinctive feature set. Additionally, this study also implies that
      there may be several changes in some particular ROIs of the brain during the AD
      development.

PMID- 29059924
TI  - Music and the brain - design of an MEG compatible piano.
AB  - Magnetoencephalography (MEG) neuroimaging has been used to study subjects'
      responses when listening to music, but research into the effects of playing music
      has been limited by the lack of MEG compatible instruments that can operate in a
      magnetically shielded environment without creating electromagnetic interference.
      This paper describes the design and preliminary testing of an MEG compatible
      piano keyboard with 25 full size keys that employs a novel 3-state optical
      encoder design and electronics to provide realistic velocity-controlled volume
      modulation. This instrument will allow researchers to study musical performance
      on a finer timescale than fMRI and enable a range of MEG studies.

PMID- 29059925
TI  - Three-way ROC validation of rs-fMRI visual information propagation transfer
      functions used to differentiate between RRMS and CIS optic neuritis patients.
AB  - Resting-state fMRI (rs-fMRI) measures the temporal synchrony between different
      brain regions while the subject is at rest. We present an investigation using
      visual information propagation transfer functions as potential optic neuritis
      (ON) markers for the pathways between the lateral geniculate nuclei, the primary
      visual cortex, the lateral occipital cortex and the superior parietal cortex. We
      investigate marker reliability in differentiating between healthy controls and ON
      patients with clinically isolated syndrome (CIS), and relapsing-remitting
      multiple sclerosis (RRMS) using a three-way receiver operating characteristics
      analysis. We identify useful and reliable three-way ON related metrics in the rs
      fMRI low-frequency band 0.0 Hz to 0.1 Hz, with potential markers associated with
      the higher frequency harmonics of these signals in the 0.1 Hz to 0.2 Hz and 0.2
      Hz to 0.3 Hz bands.

PMID- 29059926
TI  - Feasibility study of imaging fast neural activity in retinal tissue using
      Electrical Impedance Tomography.
AB  - Electrical Impedance Tomography has been recently applied to image fast neural
      activity in the somatosensory cerebral cortex. This non-invasive imaging modality
      has the unique advantage of high spatial-temporal resolution in millimeters over
      milliseconds. This work was designed to test an existing 32-channel EIT system, a
      modified UCL ScouseTom, and to discuss the feasibility of imaging neural activity
      in retinal tissue through computer simulation. The finite element method was used
      to model a retinal slice with a realistic conductivity-depth profile of the
      macaque eye. The conductivity perturbation was simulated in five different layers
      of the model. 5MUVRMS white noise was added to boundary voltages. Simulation
      results showed that it is feasible to apply EIT in retinal tissue but the
      injection current is near threshold of unwanted phosphenes induction. Therefore
      the suggested future work are validating threshold current through animal
      experiments, developing electrodes with low contact impedance and mitigating
      noise through averaging.

PMID- 29059927
TI  - Evaluating network brain connectivity in alcohol postdependent state using
      Network-Based Statistic.
AB  - The use of functional magnetic resonance imaging (fMRI) to measure spontaneous
      fluctuations in blood oxygen level dependent (BOLD) signals has become an
      indispensable tool to investigate how brain regions interact and form long-range
      networks. Statistical dependency measures between brain regions obtained from
      BOLD signals can inform about brain functional states in longitudinal studies of
      neurological and psychiatric disorders. Furthermore, its non-invasive nature
      allows comparable measurements in clinical and animal studies, providing
      excellent translational capabilities. In the present study, we apply Network
      Based Statistic (NBS) to investigate alterations in the functional connectivity
      (FC) of the rat brain in a post-dependent (PD) state, an established animal model
      of clinical relevant features in alcoholism. In contrast to mass-univariate
      tests, in which comparisons are performed at single link-level, NBS enhances the
      statistical power by assuming that the connections comprising the effect of
      interest are interconnected. Brain-wide resting-state fMRI signals were collected
      in 14 controls and 13 PD rats, and Pearson correlations computed between 47 brain
      regions of interest (ROIs). The NBS analysis revealed statistically significant
      differences in a connected network of structures including hippocampus, amygdala,
      lateral hypothalamus and the raphe nucleus, all regions with known relevance for
      addictive behaviors. In contrast, no individual connection could be found
      significant by univariate comparisons with false discovery rate (FDR) correction.
      Correlations between the structures in the identified subnetwork tend to decrease
      or become negative (anti-correlated) in the PD state compared to controls. We
      interpret this result as evidence for a disconnected subnetwork in the PD state.

PMID- 29059928
TI  - Relationship between amplitude of resting-state fNIRS global signal and EEG
      vigilance measures.
AB  - Most of the prior studies of functional connectivity in both healthy and diseased
      brain utilized resting-state functional magnetic resonance imaging (fMRI) as a
      measure to represent the temporal synchrony in blood oxygenation level dependent
      (BOLD) signals across brain regions. To eliminate the impact of widely
      distributed global signal component across the brain, many studies have adopted
      global signal regression (GSR) as a pre-processing approach to regress the global
      signal component out of BOLD signals followed by computing hemodynamic
      connectivity. However, the procedure of global signal regression has been debated
      as physiologically relevant component may be present in global signal. In this
      study, we aimed to address the controversy of global signal using functional non
      invasive neuroimaging technology, i.e. functional near-infrared spectroscopy
      (fNIRS), which measures hemodynamic signals by probing local changes in oxygen
      consumption, a common imaging contrast measured by BOLD fMRI. In the current
      study, we acquired simultaneous EEG and fNIRS signals, both in high-density
      configuration and whole-brain coverage, in healthy individuals at eyes-open and
      eyes-closed resting state and at three different body positions. We explored the
      underlying relationship between fNIRS global signal and EEG vigilance, and have
      identified negative correlation between fNIRS global signal and EEG vigilance
      across the physiological variations of measurements.

PMID- 29059929
TI  - Assessment of chemoradiotherapy response in glioma with magnetic resonance amide
      proton transfer imaging in a rodent model.
AB  - Magnetic resonance amide proton transfer (APT) imaging has proved its potential
      for detecting tumors and evaluating treatment response by depicting chemical
      exchange saturation transfer effect between the endogenous protein/peptide amide
      proton and bulk water. However, conventional asymmetry analysis for APT effect
      measurement is susceptible to concomitant contributions, particular semisolid
      magnetic transfer (MT) and nuclear overhauser effect. In this study, dominant
      saturation transfer (ST) effects, including direct water saturation and MT, were
      estimated from a sum of two Lorentzian functions. APT effect was then quantified
      by subtracting the Z-spectrum with the two ST effects. Feasibility of the method
      in the assessment of glioma therapeutic response was investigated in a rodent
      model at 3 Tesla.

PMID- 29059930
TI  - EEG source estimation accuracy in presence of simulated cortical lesions.
AB  - Methods to reconstruct the neuroelectrical activity in the brain source space can
      be used to improve the spatial resolution of scalp-recorded EEG and to estimate
      the locations of electrical sources in the brain. This procedure can improve the
      investigation of the functional organization of the human brain, exploiting the
      high temporal resolution of EEG to follow the temporal dynamics of information
      processing. As for today, the uncertainties about the effects of inhomogeneities
      due to brain lesions preclude the adoption of EEG functional mapping on patients
      with lesioned brain. The aim of this work is to quantify the accuracy of a
      distributed source localization method in recovering extended sources of
      activated cortex when cortical lesions of different dimensions are introduced in
      simulated data. For this purpose, EEG source-distributed activity estimated from
      real data was modified including silent lesion areas. Then, for each simulated
      lesion, forward and inverse calculations were carried out to localize the
      produced scalp activity and the reconstructed cortical activity. Finally, the
      error induced in the reconstruction by the presence of the lesion was computed
      and analyzed in relation to the number of electrodes and to the size of the
      simulated lesion. Results returned values of global error in the whole cortex and
      of error in the non-lesioned area which are strongly dependent on the number of
      recorded scalp sensors, as they increase when a lower spatial sampling is
      performed on the scalp (64 versus 32 EEG channels). For increasing spatial
      sampling frequencies, the accuracy of the source reconstruction improves and even
      the presence of small lesions induces significantly higher error levels with
      respect to the lesion-free condition.

PMID- 29059931
TI  - Structure and location preserving topological representation with applications on
      CT segmentation.
AB  - Contour tree represents the nesting relations of the individual components in the
      image; however, it neglects the geometric structure of the terrain. In this
      paper, we propose a new topological representation that provides the nesting and
      spatial relations of regions for CT image interpretation. The tree is constructed
      based on the signed distance transformation of binary CT image, and combines
      intensity based contour tree and a new gradient based topology tree. We also
      investigate the application of the topological representation as a constraint in
      target object segmentation. Ten non-small cell lung tumor CT studies were used
      for segmentation accuracy evaluation. The image representation results showed
      that the proposed tree structure retained the nesting and spatial relations of
      the tissues or objects in the CT image. The segmentation results demonstrated its
      usability in the separation of adjacent objects with similar intensity
      distributions.

PMID- 29059932
TI  - Monte Carlo simulation of radiation dose distribution in X-ray imaging at
      Shanghai Synchrotron Radiation Facility.
AB  - The aim of this study is to investigate the dose distribution in the process of X
      ray imaging at Shanghai Synchrotron Radiation Facility. We used the Monte Carlo
      software EGSnrc based on the statistics of the beamline BL13W to simulate the
      actual irradiation environment and calculate the dose distribution. Three
      different sizes of sources and two different tomographic models were created to
      predict the dose distribution at different regions of interest (ROI) with
      different fields of view (FOV). The simulation results showed that the dose in
      ROI is higher. The dose accumulated in the ROI with smaller FOV was more
      concentrated and relatively smaller compared with the larger FOV. This calculated
      dose distribution provides guidance for in-vivo animal experiments and other
      applications such as microbeam therapy.

PMID- 29059933
TI  - A novel pixel value space statistics map of the pulmonary nodule for
      classification in computerized tomography images.
AB  - Accurate assessment of pulmonary nodules can help to diagnose the serious degree
      of lung cancer. In most computed aided diagnosis (CADx) systems, the feature
      extraction module plays quite an important role in classifying pulmonary nodules
      based on different attributes of them. To precisely evaluate the malignancy of an
      unknown pulmonary nodule, this paper first proposes a novel pixel value space
      statistics map (PVSSM) for pulmonary nodules classification. By means of PVSSM
      this study can transform an original two-dimensional (2D) or three-dimensional
      (3D) pulmonary nodule into a 2D feature matrix, which contributes to better
      classifying a pulmonary nodule. To validate the proposed method, this study
      assembled 5385 valid 3D nodules from 1006 cases in LIDC-IDRI database. This study
      extracts sets of features from the created feature matrixes by singular value
      decomposition (SVD) method. Using several popular classifiers including KNN,
      random forest and SVM, we acquire the classification accuracies of 77.29%, 80.07%
      and 84.21%, respectively. Moreover, this study also utilizes the convolutional
      neural network (CNN) to assess the malignancy of nodules and the sensitivity,
      specificity and area under the curve (AUC) reach up to 86.0%, 88.5% and 0.913,
      respectively. Experiments demonstrate that the PVSSM has a benefit for nodules
      classification.

PMID- 29059934
TI  - Dose calculation in computerized tomography.
AB  - The purpose of this work is to develop an automatic methodology to obtain the
      dose received by a patient, (classified by organs), after being subjected to
      ionizing radiation because of CT images acquisition. The methodology starts from
      CT images, these images are automatically segmented and voxelized taking into
      account the CT numbers in order to obtain a 3D model used in Monte Carlo
      Simulations to calculate the dose inside the patient.Monte Carlo codes used in
      this work are MCNP.6.1.1, (whose results will be taken as a reference values) and
      MC-GPU, which appears to be a good candidate to be implemented in the methodology
      since his GPU parallelization offers a high speed calculation. Results show good
      agreement between simulated values obtained by MC-GPU and MCNP6.1.1.

PMID- 29059935
TI  - Intervertebral disc detection in X-ray images using faster R-CNN.
AB  - Automatic identification of specific osseous landmarks on the spinal radiograph
      can be used to automate calculations for correcting ligament instability and
      injury, which affect 75% of patients injured in motor vehicle accidents. In this
      work, we propose to use deep learning based object detection method as the first
      step towards identifying landmark points in lateral lumbar X-ray images. The
      significant breakthrough of deep learning technology has made it a prevailing
      choice for perception based applications, however, the lack of large annotated
      training dataset has brought challenges to utilizing the technology in medical
      image processing field. In this work, we propose to fine tune a deep network,
      Faster-RCNN, a state-of-the-art deep detection network in natural image domain,
      using small annotated clinical datasets. In the experiment we show that, by using
      only 81 lateral lumbar X-Ray training images, one can achieve much better
      performance compared to traditional sliding window detection method on hand
      crafted features. Furthermore, we fine-tuned the network using 974 training
      images and tested on 108 images, which achieved average precision of 0.905 with
      average computation time of 3 second per image, which greatly outperformed
      traditional methods in terms of accuracy and efficiency.

PMID- 29059936
TI  - Extract-and-match geometric corner and step pattern approach for registration of
      fluoroscopic X-ray sequences.
AB  - This paper presents a method to extract-and-match robust corner features based on
      connecting edges from the edge maps, mainly formed by coronary vascular junctions
      in fluoroscopic x-ray sequence images. Such images are challenging due to the
      aperture problem. To overcome this, existing approaches attempt to extract
      vessels for registration. However, they are ineffective in poor quality images.
      Our approach describes the extracted robust corner features in a rotation
      invariant manner using step patterns, followed by matching them effectively.
      Experimental results show that our approach performs very well (above 80%) in a
      dataset of poor quality fluoroscopic x-ray image sequences without extensive
      processing such as segmentation or learning.

PMID- 29059937
TI  - Non-local means filter denoising for DEXA images.
AB  - Dual high and low energy images of Dual Energy X-ray Absorptiometry (DEXA) suffer
      from noises due to the use of weak amount of X-rays. Denoising these DEXA images
      could be a key process to enhance and improve a Bone Mineral Density (BMD) map
      which is derived from a pair of high and low energy images. This could further
      improve the accuracy of diagnosis of bone fractures, osteoporosis, and etc. In
      this paper, we present a denoising technique for dual high and low energy images
      of DEXA via non-local means filter (NLMF). The noise of dual DEXA images is
      modeled based on both source and detector noises of a DEXA system. Then, the
      parameters of the proposed NLMF are optimized for denoising utilizing the
      experimental data from uniform phantoms. The optimized NLMF is tested and
      verified with the DEXA images of the uniform phantoms and real human spine. The
      quantitative evaluation shows the improvement of Signal-to-Noise Ratio (SNR) for
      the high and low phantom images on the order of 30.36% and 27.02% and for the
      high and low real spine images on the order of 22.28% and 33.43%, respectively.
      Our work suggests that denoising via NLMF could be a key preprocessing process
      for clinical DEXA imaging.

PMID- 29059938
TI  - Automatic vertebrae localization from CT scans using volumetric descriptors.
AB  - The localization and identification of vertebrae in spinal CT images plays an
      important role in many clinical applications, such as spinal disease diagnosis,
      surgery planning, and post-surgery assessment. However, automatic vertebrae
      localization presents numerous challenges due to partial visibility, appearance
      similarity of different vertebrae, varying data quality, and the presence of
      pathologies. Most existing methods require prior information on which vertebrae
      are present in a scan, and perform poorly on pathological cases, making them of
      little practical value. In this paper we describe three novel types of local
      information descriptors which are used to build more complex contextual features,
      and train a random forest classifier. The three features are progressively more
      complex, systematically addressing a greater number of limitations of the current
      state of the art.

PMID- 29059939
TI  - Development of semi-automatic procedure for detection and tracking of fiducial
      markers for orofacial kinematics during natural feeding.
AB  - Feeding is a highly complex, essential behavior for survival in all species.
      Characterization of feeding behaviors has implications in basic science and
      translational medicine. We have been developing methods to study feeding
      behaviors using high speed videofluoroscopy (XROMM) in rats while self-feeding
      radiopaque flavored kibble. The rat is a popular model in translational medicine;
      however, it has not been studied using this methodology. Towards this goal, we
      surgically implanted radiopaque fiducial markers into the skull, mandible, and
      tongue of rats to enable motion tracking. We are developing computer vision tools
      to extract kinematics and behavioral features from XROMM videos to overcome
      barriers of current analysis methods. By understanding feeding dynamics, we will
      gain basic scientific knowledge and translational insights for feeding disorders
      caused by neurological conditions such as ALS, Parkinson's disease, and stroke.

PMID- 29059940
TI  - Patient-specific respiratory motion estimation using Sparse Motion Field
      Presentation.
AB  - Respiratory motion estimation plays a significant role in radiation therapy.
      Previous motion estimation approaches usually depended on 4DCT, which introduced
      extra radio dose for patients, and the local motion details were ignored in the
      statistical model. In this paper, we propose a novel estimation framework, which
      employs the Sparse Motion Field Presentation (SMFP) method to obtain a coarse
      motion estimation which preserves patient-specific respiratory motion details and
      an Adaptive Variable Coefficient (AVC) motion prior registration approach is
      applied for the accurate estimation. The experimental results show that the
      proposed framework effectively preserved the local motion details and achieved
      more accurate motion estimations compared to the Mean Motion Model (MMM) and the
      Principal Component Analysis (PCA) model. We achieved motion estimations for
      diaphragmatic breathing type, thoracic breathing type and mixed type,
      respectively. The accuracy measured in the average symmetric surface distance
      (standard deviation) were 1.9(0.9) mm, 2.4(1.1) mm and 2.2(1.0) mm, when the sum
      of squared intensity difference (SSD) were 5.0, 6.1 and 5.6, respectively.

PMID- 29059941
TI  - A novel hybrid approach for reconstruction of coronary bifurcations using
      angiography and OCT.
AB  - The aim of this study is to present a new method for three-dimensional (3D)
      reconstruction of coronary bifurcations using biplane Coronary Angiographies and
      Optical Coherence Tomography (OCT) imaging. The method is based on a five step
      approach by improving a previous validated work in order to reconstruct coronary
      arterial bifurcations. In the first step the lumen borders are detected on the
      Frequency Domain (FD) OCT images. In the second step a semi-automated method is
      implemented on two angiographies for the extraction of the 2D bifurcation
      coronary artery centerline. In the third step the 3D path of the bifurcation
      artery is extracted based on a back projection algorithm. In the fourth step the
      lumen borders are placed onto the 3D catheter path. Finally, in the fifth step
      the intersection of the main and side branches produces the reconstructed model
      of the coronary bifurcation artery. Data from three patients are acquired for the
      validation of the proposed methodology and the results are compared against a
      reconstruction method using quantitative coronary angiography (QCA). The
      comparison between the two methods is achieved using morphological measures of
      the vessels as well as comparison of the wall shear stress (WSS) mean values.

PMID- 29059942
TI  - Characterization of dental pathologies using digital panoramic X-ray images based
      on texture analysis.
AB  - Dental caries and the cysts of jaws are frequently occurring pathologies
      encountered in a dental practice. Imaging of these dental anomalies is done with
      radiographic examination. Panoramic radiography/ Orthopantomography (OPG) is a
      common modality to screen patients with an advantage of ease of imaging and
      reduced exposure to patients. The panoramic images obtained with this equipment
      are exploited by noise embedded during its acquisition making the detection of
      this dental caries difficult. Detection and characterization of dental caries and
      various other maxilla-facial pathologies can be achieved by the application of
      computer aided image processing algorithms applied on dental panoramic images.
      This paper presents two distinct image processing algorithms for detection of
      dental anomalies. The first part of this paper presents a novel approach for
      detection of dental caries using hybridized negative transformation. The second
      part of paper presents, statistical texture analysis for the dental images
      containing cysts along with dental caries. The texture analysis is used when the
      objects to be segmented based on texture content rather than intensities. The
      texture of panoramic image is characterized by Gray Level Co-occurrence Matrix
      (GLCM). The texture features obtained from the GLCM are energy, entropy,
      homogeneity, contrast and correlation. These texture features can be used to find
      texture boundaries to obtain segmentation about the region of cysts. Results
      obtained by both the methods were satisfactory correlating with the diagnosis
      made by the maxillofacial radiologists.

PMID- 29059943
TI  - Glaucoma classification from retina optical coherence tomography angiogram.
AB  - This paper presents a new method for classification of retina into glaucoma and
      non-glaucoma cases based on optical coherence tomography angiogram (OCTA). The
      key idea here is to analyze the retinal microvasculature in the optic disc area
      of an enface OCTA for glaucoma classification. To facilitate this analysis, we
      propose a way to extract a so-called "optic disc microvasculature" region and
      then propose several features that will be extracted from this microvasculature
      region. A machine classifier is then trained using the designated features and
      subsequently used to classify the OCTA data. We show that our proposed approach
      works well on the tested dataset.

PMID- 29059945
TI  - Hair and bare skin discrimination for laser-assisted hair removal systems.
AB  - Laser-assisted hair removal devices aim to remove body hair permanently. In most
      cases, these devices irradiate the whole area of the skin with a homogenous power
      density. Thus, a significant portion of the skin, where hair is not present, is
      burnt unnecessarily causing health risks. Therefore, methods that can distinguish
      hair regions automatically would be very helpful avoiding these unnecessary
      applications of laser. This study proposes a new system of algorithms to detect
      hair regions with the help of a digital camera. Unlike previous limited number of
      studies, our methods are very fast allowing for real-time application. Proposed
      methods are based on certain features derived from histograms of hair and skin
      regions. We compare our algorithm with competing methods in terms of localization
      performance and computation time and show that a much faster real-time accurate
      localization of hair regions is possible with the proposed method. Our results
      show that the algorithm we have developed is extremely fast (around 45
      milliseconds) allowing for real-time application with high accuracy hair
      localization ( 96.48 %).

PMID- 29059944
TI  - Analyzing orientation patterns of human skin fibroblasts using image gradient
      information.
AB  - Fibroblasts are the cells within the dermis layer of skin which are responsible
      for generating connective tissue, where collagen is the main component. However,
      the effects of collagen on the motion behavior of human skin fibroblasts were not
      studied well. We therefore propose an image analysis method to quantify the
      effects of collagen on the motion characteristics of fibroblasts. Images are
      divided into disjoint blocks and three gradient based descriptors, namely
      histogram of oriented gradients (HOG), the modified HOG (modiHOG), and the
      gradient direction histogram (GDH) are then applied to each block. These features
      can extract the orientation and shape or orientation only information of the skin
      fibroblasts from images. An orientation similarity function and a quantitative
      index, called first minimum similarity distance, are defined to quantify the
      orientation behavior of fibroblasts. An experiment with two sets of fibroblasts
      images, obtained from cell culture with and without collagen coating,
      demonstrates that the skin fibroblasts produce smaller orientation patterns, when
      they are cultured in the presence of collagen proteins. A statistical t-test is
      then performed, which validates the significant differences in the orientation
      behavior of the skin fibroblasts in the two cases mentioned.

PMID- 29059946
TI  - Fully automated detection of lamina cribrosa in optical coherence tomography:
      Framework and illustrative examples.
AB  - We present an algorithm for automated detection of lamina cribrosa (LC) using
      optical coherence tomography scans. To the best of our knowledge, it is the first
      algorithm of this type, as previous attempts relied heavily on characteristic
      points marked a priori by a human expert and were hence semi-automated at best.
      First, we highlight the unwanted, yet unavoidable, influence of image rescaling
      necessary to provide the detection algorithm with real-world image proportions.
      Next, we simulate an LC phantom and test the influence of various combinations of
      the rescaling method and SNRs on the LC detection efficacy. Finally, we present
      some illustrative results from real-data analysis.

PMID- 29059947
TI  - Stability assessment of first order statistics features computed on ADC maps in
      soft-tissue sarcoma.
AB  - Radiomics extracts a large number of features from medical images to perform a
      quantitative characterization. Aim of this study was to assess radiomic features
      stability and relevance. Apparent diffusion coefficient (ADC) maps were computed
      from diffusion-weighted magnetic resonance images (DW-MRI) of 18 patients
      diagnosed with soft-tissue sarcomas (STSs). Thirty-seven intensity-based features
      were computed on the regions of interest (ROIs). First, ROIs of the images were
      subjected to translations and rotations in specific ranges. The 37 features
      computed on the original and transformed ROIs were compared in terms of
      percentage of variations. The intra-class correlation coefficient (ICC) was
      computed. To be accepted, a feature should satisfy the following conditions: the
      ICC after a minimum entity transformation is > 0.6 and the ICC after a maximum
      entity translation is <; 0.4. In total, 31 features out of 37 were accepted by
      the algorithm. This stability analysis can be used as a first step in the
      features selection process.

PMID- 29059948
TI  - A mRMRMSRC feature selection method for radiomics approach.
AB  - Radiomics can convert digital images to mineable data by extracting a huge number
      of image features. Because of the high dimensions of radiomics features, feature
      selection is a very important step which affects the performance of the final
      prediction or classification. In this paper, we propose a feature selection
      criterion for radiomics analysis of glioma based on Magnetic Resonance Image
      (MRI). The proposed method named as minimum Redundancy, Maximum Relevance and
      Maximum Sparse Representation Coefficient (mRMRMSRC) criterion, which take three
      factors into consideration at the same time: relevance between features and
      labels with or without the influence of all other features, and redundancy
      between each couple of features. Different from traditional feature selection
      method, the mRMRMSRC manifests the best performance compared with the methods
      based on sparse representation coefficient (SRC), minimum redundancy maximum
      relevance (mRMR), F_score and ReliefF. We conducted our methods on glioma
      Isocitrate Dehydrogenase 1 (IDH1) estimation. The experiment showed that mRMRMSRC
      produced area under the ROC curve (AUC) of 90% compared with 77%-89% of state-of
      art methods.

PMID- 29059949
TI  - Application of MRI texture analysis in the study of the posterior fossa tumors
      growing trend in children.
AB  - In order to analyze the growing trend of the posterior fossa tumor in children
      and provide assistant basis for the treatment or surgery of tumors, a variety of
      texture analysis methods were comprehensive used to analyze and identify three
      kinds of brain tissues, tumor region, tumor diffusion region and normal brain
      tissue region. The MRIs of tumor patients were collected to extract texture
      features. Then feature selection method CFS and feature compression method
      partial least squares regression (PLSR) were used to process these feature space.
      Finally, different classification methods were used to identify three classes
      samples expressed in different forms. The classification results of all features
      show that texture analysis can be used to analyze the growing trend of the tumor
      and provide sufficient support for the prediction of it. The CFS subsets results
      show that the specific texture features have important value for qualitative
      analysis and discrimination of three kinds of tissues. PLSR compressed sets
      results confirm the above results and provide intuitive display of compressed
      sample space distribution.

PMID- 29059950
TI  - Preoperative parathyroid localization using joint planar imaging.
AB  - The conventional approach for preoperative parathyroid localization with the dual
      99mTc-sestamibi (99mTc-MIBI) and 99mTc-pertechnetate (99mTcO4- ) scintigraphy
      technique obtains the differential image by subtracting images from the two
      scans; the former depicts both the thyroid and parathyroid glands while the
      latter depicts the thyroid only. In this study, we developed a novel method based
      on Poisson noise modeling and maximum-likelihood estimation to generate the
      differential image in an iterative fashion using both planar images jointly. We
      demonstrated improved performance of our joint method as compared with the
      subtraction method in both phantom and patient studies. In the phantom study, we
      acquired two noise-free planar datasets using 99mTc on an in-house thyroid
      phantom and a "lesion" bead (representing a parathyroid gland) with the same
      attenuation background as the thyroid phantom. These two planar datasets were
      combined and scaled to simulate noise-free clinical MIBI (four lesion-to
      background contrast (LBC) values: 1.2, 1.3, 1.4 and 1.5), and 99mTcO4- datasets.
      One-hundred Poisson noise realizations were generated for each datasets. The mean
      and standard deviation (SD) of the lesion contrast in the differential images
      were computed for both the subtraction and the joint methods. We also applied
      both the subtraction and the joint methods to one parathyroid patient dataset.
      The voxel-wise mean-to-SD ratios in four hyperfunctioning parathyroid lesions
      were calculated. The phantom results showed that the joint method at the 50th
      iteration yielded a significant SD reduction compared with the subtraction method
      ranging from 20% to 45% (p <; 0.05). Similarly, the voxel-wise mean-to-SD ratios
      were substantially improved in the patient study from 0.40-1.60 (subtraction) to
      2.68-3.16 (joint).

PMID- 29059951
TI  - Fully automated blink detection for uveal melanoma radiotherapy.
AB  - Uveal melanoma is a widespread neoplasm in the eye that cause vision defects. The
      disease may result in loss of eye, even loss of life with a risk of metastasis to
      other tissues. There have been proposed various treatment methods to overcome the
      disease including enucleation and radiotherapy. Radiotherapy treatment is
      certainly preferable since it avoids the loss of eye. The treatment is applied
      with radioactive beam directed to the tumor, and thus the eye must be kept steady
      usually with local anesthesia. However, anesthesia has many health risks;
      therefore it is preferable to perform this operation without it. This paper
      presents an approach where a camera will be recording the eye and the
      radiotherapy will immediately be halted when the eye is closed to avoid
      unnecessary beams directed to healthy regions of the eye. System is based on the
      classification of the acquired image frames as "eye open" and "eye closed". The
      speed of the algorithm is aimed as close as possible to real time so that it can
      respond instantly to any change in present eye state. A total of 480 video
      frames, 120 frames for each open and closed eyes in bright and dark lighting
      conditions separately, were used for experimentation. Test results indicate that
      developed features are successful in terms of being very fast providing no
      classification error.

PMID- 29059952
TI  - Automated ovarian follicular monitoring: A novel real-time approach.
AB  - Ovarian follicular monitoring is an essential diagnostic tool in obstetrics and
      gynecology to evaluate ovarian reserve and to estimate follicular and ovarian
      response to fertility treatment. Given the significant time requirement,
      inconvenience measuring follicles and estimating follicular development during
      multiple examinations, and variable results of different clinicians performing
      monitoring, complete automation of follicular monitoring is necessary.
      Computerized follicle detection is currently either semi-automated or has low
      performance due to limiting factors: (1) noise, (2) detecting multiple follicles
      very close to each other as one follicle region without finding the boundary of
      individual follicles, and (3) not being fast enough to be used in real-time
      clinical practice. To overcome these limitations, we handle noise by singular
      value decomposition based image compression followed by an anisotropic diffusion
      scheme for multiplicative speckle, and detect follicles by performing different
      segmentation techniques depending on features of the image (such as pixel
      intensity level) and features of the detected follicle areas (such as roundness).
      This approach allows for rapid identification and measurement of individual
      follicles with the ability to differentiate between the borders of adjacent
      follicles and the boundary between the follicle and ovarian stroma.

PMID- 29059953
TI  - An embedded system for image segmentation and multimodal registration in
      noninvasive skin cancer screening.
AB  - We present a heterogeneous architecture for image registration and multimodal
      segmentation on an embedded system for noninvasive skin cancer screening. The
      architecture combines Otsu thresholding and the random walker algorithm to
      perform image segmentation, and features a hardware implementation of the Harris
      corner detection algorithm to perform region-of-interest detection and image
      registration. Running on a Xilinx XC7Z020 reconfigurable system-on-a-chip, our
      prototype computes the initial segmentation of a 400*400-pixel region of interest
      in the visible spectrum in 12.1 seconds, and registers infrared images against
      this region at 540 frames per second, while consuming 1.9W.

PMID- 29059954
TI  - Automated lesion segmentation and dermoscopic feature segmentation for skin
      cancer analysis.
AB  - Segmentation is the first and most important task in computer-based diagnosis of
      skin cancer since other tasks are relied mainly on accurately segmented lesions.
      Recently, deep learning as a mainstream method in machine learning has shown
      promising results on semantic image segmentation. In this paper, we demonstrate
      applying deep convolutional networks to two main segmentation tasks in melanoma
      diagnosis, a lesion segmentation task followed by a lesion dermoscopic feature
      segmentation task. The proposed method is evaluated on a database from ISBI
      challenge 2016. By using a hybrid model, computation load for the second task
      decreases and masks provided by lesion segmentation have been used to enhance the
      results for the feature segmentation task as well. The results are close to the
      best results of ISBI challenge 2016. The proposed model yields quite promising
      results although it is based on very initial hybrid model without an aggressive
      fine-tuning that is heavily required in Deep Learning implementations. Therefore,
      there is a room for further improvements.

PMID- 29059955
TI  - Robust MR image segmentation using the trimmed likelihood estimator in asymmetric
      Student's-t mixture model.
AB  - Finite mixture model (FMM) has been widely used for unsupervised segmentation of
      magnetic resonance (MR) images in recent years. However, in real applications,
      the distribution of the observed data usually contains an unknown fraction of
      outliers, which would interfere with the estimation of the parameters of the
      mixture model. The statistical model-based technique which provides a
      theoretically well segmentation criterion in presence of outliers is the mixture
      modeling and the trimming approach. Therefore, in this paper, a robust estimation
      of asymmetric Student's-t mixture model (ASMM) using the trimmed likelihood
      estimator for MR image segmentation has been proposed. The proposed method is
      supposed to discard the outliers, and then to estimate the parameters of the ASMM
      with the remaining samples. The advantages of the proposed algorithm are that its
      robustness to dispose the disturbance of outliers and its flexibility to describe
      various shapes of data. Finally, expectation-maximization (EM) algorithm is
      adopted to maximize the log-likelihood and to obtain the estimation of the
      parameters. The experimental results show that the proposed method has a better
      performance on the segmentation of synthetic data and real MR images.

PMID- 29059956
TI  - Semi-automated enhanced breast tumor segmentation for CT image.
AB  - Accurate detection of breast cancer region is essential for treatment. X-ray
      computed tomography (CT) is an effective diagnostic method of breast cancer
      besides MRI and ultrasound. In this paper, a semi-automated breast cancer
      segmentation method was proposed to CT images. First, maximum region searching
      was used to find the rough boundary of the lesion. Then, a modified Histogram
      Equalization with Iterative-Filling was adopted to enhance the lesion and avoid
      the unbalanced intensity in the target region. Finally, a four-seeds Random Walk
      was used for accurate segmentation. The method was validated on a clinical
      dataset with 50 cases containing 630 slices in total. The experiments showed that
      the Dice Coefficient of our method was 88.6%, which was higher than that of
      Random Walk (76.9%) and Graph-Cut (79.8%).

PMID- 29059957
TI  - Cardiac image segmentation using generalized polynomial chaos expansion and level
      set function.
AB  - Cardiovascular Magnetic Resonance (CMR) images involves a great amount of
      uncertainties. Such uncertainties may originate from either intrinsic measurement
      limitations or heterogeneities among patients. Without properly considering these
      uncertainties, image analysis may provide inaccurate estimations of cardiac
      functions, and ultimately lead to false diagnosis and inappropriate treatment
      strategy. In this work, a stochastic image segmentation algorithm is developed to
      separate cardiac chambers from the background of CMR images. To account for noise
      and uncertainties in pixel values, a generalized polynomial chaos (gPC) expansion
      is integrated with a level set function to dynamically evolve boundaries of
      cardiac chambers. Two consecutive steps are developed: a deterministic
      segmentation to identify an immediate neighborhood of boundary, of which pixel
      values are used to calibrate the gPC model; and a stochastic segmentation applied
      to the neighborhood region to evolve boundaries of cardiac chambers in a
      stochastic manner. The proposed method can provide a probabilistic description of
      the segmented heart boundary, which will greatly improve the reliability of image
      analysis, and potentially enhanced cardiac function evaluation.

PMID- 29059958
TI  - Using cystoscopy to segment bladder tumors with a multivariate approach in
      different color spaces.
AB  - Nowadays the diagnosis of bladder lesions relies upon cystoscopy examination and
      depends on the interpreter's experience. State of the art of bladder tumor
      identification are based on 3D reconstruction, using CT images (Virtual
      Cystoscopy) or images where the structures are exalted with the use of
      pigmentation, but none uses white light cystoscopy images. An initial attempt to
      automatically identify tumoral tissue was already developed by the authors and
      this paper will develop this idea. Traditional cystoscopy images processing has a
      huge potential to improve early tumor detection and allows a more effective
      treatment. In this paper is described a multivariate approach to do segmentation
      of bladder cystoscopy images, that will be used to automatically detect and
      improve physician diagnose. Each region can be assumed as a normal distribution
      with specific parameters, leading to the assumption that the distribution of
      intensities is a Gaussian Mixture Model (GMM). Region of high grade and low grade
      tumors, usually appears with higher intensity than normal regions. This paper
      proposes a Maximum a Posteriori (MAP) approach based on pixel intensities read
      simultaneously in different color channels from RGB, HSV and CIELab color spaces.
      The Expectation-Maximization (EM) algorithm is used to estimate the best
      multivariate GMM parameters. Experimental results show that the proposed method
      does bladder tumor segmentation into two classes in a more efficient way in RGB
      even in cases where the tumor shape is not well defined. Results also show that
      the elimination of component L from CIELab color space does not allow definition
      of the tumor shape.

PMID- 29059959
TI  - Retinal hemorrhage detection by rule-based and machine learning approach.
AB  - Robust detection of hemorrhages (HMs) in color fundus image is important in an
      automatic diabetic retinopathy grading system. Detection of the hemorrhages that
      are close to or connected with retinal blood vessels was found to be challenge.
      However, most methods didn't put research on it, even some of them mentioned this
      issue. In this paper, we proposed a novel hemorrhage detection method based on
      rule-based and machine learning methods. We focused on the improvement of
      detection of the hemorrhages that are close to or connected with retinal blood
      vessels, besides detecting the independent hemorrhage regions. A preliminary test
      for detecting HM presence was conducted on the images from two databases. We
      achieved sensitivity and specificity of 93.3% and 88% as well as 91.9% and 85.6%
      on the two datasets.

PMID- 29059960
TI  - Image quality classification for DR screening using deep learning.
AB  - The quality of input images significantly affects the outcome of automated
      diabetic retinopathy (DR) screening systems. Unlike the previous methods that
      only consider simple low-level features such as hand-crafted geometric and
      structural features, in this paper we propose a novel method for retinal image
      quality classification (IQC) that performs computational algorithms imitating the
      working of the human visual system. The proposed algorithm combines unsupervised
      features from saliency map and supervised features coming from convolutional
      neural networks (CNN), which are fed to an SVM to automatically detect high
      quality vs poor quality retinal fundus images. We demonstrate the superior
      performance of our proposed algorithm on a large retinal fundus image dataset and
      the method could achieve higher accuracy than other methods. Although retinal
      images are used in this study, the methodology is applicable to the image quality
      assessment and enhancement of other types of medical images.

PMID- 29059961
TI  - Deep Convolutional Neural Networks for left ventricle segmentation.
AB  - Left ventricle (LV) segmentation is crucial for quantitative cardiac function
      analysis. Manual segmentation of the endocardium and epicardium is highly
      cumbersome; physicians limit delineation to the end-diastolic and end-systolic
      phases. A fully automated system could provide an analysis of cardiac morphology
      for all phases in a much shorter time. Most of the current LV segmentation
      methods are semi-automated and require error prone manual initialization. A fully
      automated LV segmentation method would expedite the functional analysis of the
      LV, reduce subjectivity and improve patient experience. We automatically segment
      the LV wall in cardiac MRI images with a Deep Convolutional Neural Network
      (DCNN). This algorithm first calculates the probability of a pixel belonging to
      the LV wall or background and then generates a label based on those probabilities
      without manual initialization. We then compare these results to the results
      obtained with another DCNN initialization method using Gabor filters. With Gabor
      DCNN we obtain an accuracy of 0.97, specificity of 0.984, sensitivity of 0.841
      and mean accuracy of 0.902. This shows that Gabor filters perform better than
      random filters in the DCNN for LV segmentation.

PMID- 29059963
TI  - Deep tessellated retinal image detection using Convolutional Neural Networks.
AB  - Tessellation in fundus is not only a visible feature for aged-related and myopic
      maculopathy but also confuse retinal vessel segmentation. The detection of
      tessellated images is an inevitable processing in retinal image analysis. In this
      work, we propose a model using convolutional neural network for detecting
      tessellated images. The input to the model is pre-processed fundus image, and the
      output indicate whether this photograph has tessellation or not. A database with
      12,000 colour retinal images is collected to evaluate the classification
      performance. The best tessellation classifier achieves accuracy of 97.73% and AUC
      value of 0.9659 using pretrained GoogLeNet and transfer learning technique.

PMID- 29059962
TI  - Deep learning based Nucleus Classification in pancreas histological images.
AB  - Tumor specimens contain a variety of healthy cells as well as cancerous cells,
      and this heterogeneity underlies resistance to various cancer therapies. But this
      problem has not been thoroughly investigated until recently. Meanwhile,
      technological breakthroughs in imaging have led to an explosion of molecular and
      cellular profiling data from large numbers of samples, and modern machine
      learning approaches including deep learning have been shown to produce
      encouraging results by finding hidden structures and make accurate predictions.
      In this paper, we propose a Deep learning based Nucleus Classification (DeepNC)
      approach using paired histopathology and immunofluorescence images (for label),
      and demonstrate its classification prediction power. This method can solve
      current issue on discrepancy between genomic- or transcriptomic-based and
      pathology-based tumor purity estimates by improving histological evaluation. We
      also explain challenges in training a deep learning model for huge dataset.

PMID- 29059964
TI  - Development of automatic retinal vessel segmentation method in fundus images via
      convolutional neural networks.
AB  - The analysis of fundus photograph is one of useful diagnosis tools for diverse
      retinal diseases such as diabetic retinopathy and hypertensive retinopathy.
      Specifically, the morphology of retinal vessels in patients is used as a measure
      of classification in retinal diseases and the automatic processing of fundus
      image has been investigated widely for diagnostic efficiency. The automatic
      segmentation of retinal vessels is essential and needs to precede computer-aided
      diagnosis system. In this study, we propose the method which implements patch
      based pixel-wise segmentation with convolutional neural networks (CNNs) in fundus
      images for automatic retinal vessel segmentation. We construct the network
      composed of several modules which include convolutional layers and upsampling
      layers. Feature maps are made by modules and concatenated into a single feature
      map to capture coarse and fine structures of vessel simultaneously. The
      concatenated feature map is followed by a convolutional layer for performing a
      pixel-wise prediction. The performance of the proposed method is measured on
      DRIVE dataset. We show that our method is comparable to the results of other
      state-of-the-art algorithms.

PMID- 29059965
TI  - Iterative deep convolutional encoder-decoder network for medical image
      segmentation.
AB  - In this paper, we propose a novel medical image segmentation using iterative deep
      learning framework. We have combined an iterative learning approach and an
      encoder-decoder network to improve segmentation results, which enables to
      precisely localize the regions of interest (ROIs) including complex shapes or
      detailed textures of medical images in an iterative manner. The proposed
      iterative deep convolutional encoder-decoder network consists of two main paths:
      convolutional encoder path and convolutional decoder path with iterative
      learning. Experimental results show that the proposed iterative deep learning
      framework is able to yield excellent medical image segmentation performances for
      various medical images. The effectiveness of the proposed method has been proved
      by comparing with other state-of-the-art medical image segmentation methods.

PMID- 29059966
TI  - Ensemble of convolutional neural networks for classification of breast
      microcalcification from mammograms.
AB  - Human level recall performance in detecting breast cancer considering
      microcalcifications from mammograms has a recall value between 74.5% and 92.3%.
      In this research, we approach to breast microcalcification classification problem
      using convolutional neural networks along with various preprocessing methods such
      as contrast scaling, dilation, cropping etc. and decision fusion using ensemble
      of networks. Various experiments on Digital Database for Screening Mammography
      dataset showed that preprocessing poses great importance on the classification
      performance. The stand-alone models using the dilation and cropping preprocessing
      techniques achieved the highest recall value of 91.3%. The ensembles of the stand
      alone models surpass this recall value and a 97.3% value of recall is achieved.
      The ensemble having the highest F1 Score (harmonic mean of precision and recall),
      which is 94.5%, has a recall value of 94.0% and a precision value of 95.0%. This
      recall is still above human level performance and the models achieve competitive
      results in terms of accuracy, precision, recall and F1 score measures.

PMID- 29059967
TI  - Comparison of the impedance cardiogram with continuous wave radar using body
      contact antennas.
AB  - This paper describes a continuous wave (CW) radar system with body-contact
      antennas and basic signal processing. The goal is to assess the signals'
      reproducibility across different subjects as well as a respiration cycle. Radar
      signals using body-contact antennas with a carrier frequency of 868 MHz are used
      to acquire the cardiac activity at the sternum. The radar I and Q channel signals
      are combined to form their magnitude. Signals are collected from six healthy
      males during paced breathing conditions. The electrocardiogram (ECG) and
      impedance cardiogram (ICG) signals are acquired simultaneously as reference. The
      chosen feature in the radar signal is the maximum of its second derivative, which
      is closest to the ICG B-point. The median and mean absolute errors in pre
      ejection period (PEP) in milliseconds between the ICG's B-point and chosen
      feature in the radar signal range from -6-119.7 ms and 7.8-62.3 ms for all
      subjects. The results indicate that a reproducible radar signal is obtained from
      all six subjects. More work is needed on understanding the origin of the radar
      signals using ultrasound as a comparison.

PMID- 29059968
TI  - A MAC protocol with high scalability for motion capture based on frequency
      division multiple and time division multiple access.
AB  - A good performance of motion capture, which belongs to body sensor network,
      depends on a reasonable design of MAC protocol. The purpose of this study is to
      design a reliable and highly extensible protocol for applying in motion capture.
      The proposed MAC protocol can easily be actualized by the timer in the chip. With
      this MAC protocol, the network would be built quickly. One or more nodes could be
      added easily in the net or deleted randomly from the net. In order to verify the
      superiority of this protocol, a series of experiments were designed. The results
      showed that the mean of simulation receive frames for node1-node7 from each stage
      were very close to the original frames. In addition, the final Pocket Loss Rates
      for node1-node7 were 0.081%, 0.175%, 0.143%, 0.249%, 0.248%, 0.044% and 1.897%,
      which could be in the error-allowed range. Thus, this protocol is stable and
      reliable, which can be widely used to capture human movement signal.

PMID- 29059969
TI  - Modeling and characterization of different channels based on human body
      communication.
AB  - Human body communication (HBC), which uses the human body as a transmission
      medium for electrical signals, provides a prospective communication solution for
      body sensor networks (BSNs). In this paper, an inhomogeneous model which includes
      the tissue layers of skin, fat, and muscle is proposed to study the propagation
      characteristics of different HBC channels. Specifically, the HBC channels,
      namely, the on-body to on-body (OB-OB)channel, on-body to in-body (OB-IB)
      channel, in-body to on-body (IB-OB) channel, and in-body to in-body (IB
      IB)channel, are studied over different frequencies (from 1MHz to 100MHz) through
      numerical simulations with finite-difference time-domain (FDTD) method. The
      results show that the gain of OB-IB channel and IB-OB channel is almost the same.
      The gain of IB-IB channel is greater than other channels in the frequency range
      1MHz to 70MHz. In addition, the gain of all channels is associated with the
      channel length and communication frequency. The simulations are verified by
      experimental measurements in a porcine tissue sample. The results show that the
      simulations are in agreement with the measurements.

PMID- 29059970
TI  - Reever control: A biosignal controlled interface.
AB  - With the development of new technologies, new accessibility solutions have
      emerged to increase the inclusion of user with disabilities. This paper details
      the development of Reever Control, an interface based on inertial sensors and
      sEMG signal processing to control a cursor in a virtual environment. The metrics
      of time, number of false clicks and average absolute error were used to
      characterize the system and compare it with Camera Mouse, an image processing
      based interface. The Reever Control showed improvements compared to uniaxial
      control, robustness to artifacts, support of right click and runtime compatible
      with Camera Mouse.

PMID- 29059971
TI  - A 274uW clock synchronized wireless body area network IC with super-regenerative
      RSSI for biomedical ad-hoc network system.
AB  - A clock synchronized multi-node wireless body area network (WBAN) transceiver IC
      with super-regenerative RSSI is proposed for biomedical ad-hoc network system.
      The ad-hoc network makes stable communication even in the harsh human body
      channel condition (<;-50 dB attenuation) with low-power consumption. The proposed
      system consists of two types of IC - a hub and node IC. The hub IC broadcasts the
      240 MHz clock signal to the whole node ICs and gather the measured data through
      body channel communication (BCC). In the node IC, it has 2 key building blocks;
      1) Injection locking clock synchronization receiver, and 2) Super-regenerative
      RSSI (SR-RSSI) and OOK receiver. As a result, the 240 MHz clock is exactly
      synchronized in the node IC with 90 MUW power consumption. And a channel
      condition-adapted ad-hoc network is constructed based on the SR-RSSI data. SR
      RSSI consumes 184 MUW concurrent achieving OOK receiver functionality for the ad
      hoc network. The proposed WBAN IC is fabricated in 0.18 MUm CMOS technology.

PMID- 29059972
TI  - A wearable multi-pad electrode prototype for selective functional electrical
      stimulation of upper extremities.
AB  - In this paper, a surface multi-pad stimulation electrode with selective
      characteristics was designed, it was safe to use and easy to mount. Then a
      wearable and distributed multi-pad functional electrical stimulation (FES)
      prototype combined with sensing, communication and smart technology was designed,
      which can achieve a fast, intelligent optimization to determine stimulation
      electrode sites and comfortable stimulation. In addition, in order to improve the
      application and convenience of FES in the rehabilitation at clinical and home
      setting, an Android application (APP) based on smart phone was designed for
      running an algorithm of searching optimal stimulation site. The prototype has
      been validated by performing selective stimulation on one healthy subject, and
      showed that the FES system can automatically determine the stimulation site.

PMID- 29059973
TI  - A Quad-Cantilevered Plate micro-sensor for intracranial pressure measurement.
AB  - This paper proposes a new design for pressure-sensing micro-plate platform to
      bring higher sensitivity to a pressure sensor based on piezoresistive MEMS
      sensing mechanism. The proposed design is composed of a suspended plate having
      four stepped cantilever beams connected to its corners, and thus defined as Quad
      Cantilevered Plate (QCP). Finite element analysis was performed to determine the
      optimal design for sensitivity and structural stability under a range of applied
      forces. Furthermore, a piezoresistive analysis was performed to calculate sensor
      sensitivity. Both the maximum stress and the change in resistance of the
      piezoresistor associated with the QCP were found to be higher compared to
      previously published designs, and linearly related to the applied pressure as
      desired. Therefore, the QCP demonstrates greater sensitivity, and could be
      potentially used as an efficient pressure sensor for intracranial pressure
      measurement.

PMID- 29059974
TI  - A sub 125 nW sub-threshold analog adaptive sampler in 180 nm CMOS.
AB  - We present an ultra low power analogue adaptive sampler for extraction of
      features from an arterial blood pressure signal, prior to ADC operation or
      conversion. The architecture is implemented and simulated in UMC 180 nm
      technology. A worst case power consumption across process variation of 124.6 nW
      was achieved, with a process invariant key-point timing error of approximately
      2.31 ms, corresponding to a sample error of magnitude less than 0.1 mmHg,
      simulated at body temperature of 37 degrees C. This is significantly below the
      standard clinical recording accuracy of 1 mmHg for electronic measurement tools.

PMID- 29059975
TI  - A novel hardware implementation for detecting respiration rate using
      photoplethysmography.
AB  - Asthma is a serious public health problem. Continuous monitoring of breathing may
      offer an alternative way to assess disease status. In this paper we present a
      novel hardware implementation for the capture and storage of a
      photoplethysmography (PPG) signal. The LED duty cycle was altered to determine
      the effect on respiratory rate accuracy. The oximeter was mounted to the left
      index finger of ten healthy volunteers. The breathing rate derived from the
      oximeter was validated against a nasal airflow sensor. The duty cycle of a pulse
      oximeter was changed between 5%, 10% and 25% at a sample rate of 500 Hz. A PPG
      signal and reference signal was captured for each duty cycle. The PPG signals
      were post processed in Matlab to derive a respiration rate using an existing
      Matlab toolbox. At a 25% duty cycle the RMSE was <;2 breaths per minute for the
      top performing algorithm. The RMSE increased to over 5 breaths per minute when
      the duty cycle was reduced to 5%. The power consumed by the hardware for a 5%,
      10% and 25% duty cycle was 5.4 mW, 7.8 mW, and 15 mW respectively. For clinical
      assessment of respiratory rate, a RSME of <;2 breaths per minute is recommended.
      Further work is required to determine utility in asthma management. However for
      non-clinical applications such as fitness tracking, lower accuracy may be
      sufficient to allow a reduced duty cycle setting.

PMID- 29059976
TI  - A video/IMU hybrid system for movement estimation in infants.
AB  - Cerebral palsy is a non-progressive neurological disorder occurring in early
      childhood affecting body movement and muscle control. Early identification can
      help improve outcome through therapy-based interventions. Absence of so-called
      "fidgety movements" is a strong predictor of cerebral palsy. Currently, infant
      limb movements captured through either video cameras or accelerometers are
      analyzed to identify fidgety movements. However both modalities have their
      limitations. Video cameras do not have the high temporal resolution needed to
      capture subtle movements. Accelerometers have low spatial resolution and capture
      only relative movement. In order to overcome these limitations, we have developed
      a system to combine measurements from both camera and sensors to estimate the
      true underlying motion using extended Kalman filter. The estimated motion
      achieved 84% classification accuracy in identifying fidgety movements using
      Support Vector Machine.

PMID- 29059977
TI  - Running wavelet archetype aids the determination of heart rate from the video
      photoplethysmogram during motion.
AB  - The extraction of heart rate from a video-based biosignal during motion using a
      novel wavelet-based ensemble averaging method is described. Running Wavelet
      Archetyping (RWA) allows for the enhanced extraction of pulse information from
      the time-frequency representation, from which a video-based heart rate (HRvid)
      can be derived. This compares favorably to a reference heart rate derived from a
      pulse oximeter.

PMID- 29059978
TI  - Using a new PPG indicator to increase the accuracy of PTT-based continuous
      cuffless blood pressure estimation.
AB  - Pulse transit time (PTT) has been identified as a potential indicator to estimate
      blood pressure (BP) continuously and cufflessly in the previous studies, but it
      is still unsatisfactory for clinical uses. In order to improve the BP estimation
      accuracy, another candidate signal, photoplethysmogram (PPG) has been used to
      estimate continuous BP. In this study, a new PPG indicator, the intensity ratio
      of the first derivative wave of PPG (1st dPIR), was proposed and a novel BP
      estimation algorithm by using both PTT and 1st dPIR was developed with an attempt
      to further increase the BP estimation accuracy. The performance of the proposed
      algorithm was examined and validated using the ECG and PPG recordings from 22
      healthy subjects when they performed both mental arithmetic stress and Valsalva's
      manoeuvre tests that could induce their BP fluctuations. The continuous
      Finapres(r) BP were measured with a finger cuff as a referenced BP value. Our
      results showed that using the proposed BP estimation algorithm, the grand
      absolute mean and standard deviation (SD) errors between the estimated and
      referenced BP were 3.22+/-8.02 mmHg for systolic BP (SBP) and 3.13+/-4.82mmHg for
      diastolic BP (DBP). It could achieve a decrease of 0.34+/-0.27 mmHg in SBP and
      0.33+/-0.44 mmHg in DBP on the grand absolute mean and SD estimation errors in
      comparison to the state-of-the-art PPT-based method. Findings from this study
      suggest that the newly proposed PPG indicator would be promising for improving
      the accuracy of current PTT-based continuous and cuffless BP estimation
      algorithms.

PMID- 29059979
TI  - Predicting food nutrition facts using pocket-size near-infrared sensor.
AB  - Diet monitoring is one of the most important aspects in preventative health care
      that aims to reduce various health risks. Manual recording has been a prevalence
      among all approaches yet it is tedious and often end up with a low adherence
      rate. Several existing techniques that have been developed to monitor food intake
      suffer too with accuracy, efficiency, and user acceptance rate. In this paper we
      propose a novel approach on measuring food nutrition facts, through a pocket-size
      non-intrusive near-infrared (NIR) scanner. We build efficient regression models
      that can make quantitative prediction on food nutrition contents, such as energy
      and carbohydrate. Our extensive experiments on off-the-shelf liquid foods
      demonstrates the accuracy of these regression models and proves the applicability
      of using NIR spectra that are collected by small hand-held scanner, on food
      nutrition prediction.

PMID- 29059980
TI  - Affordable sensor based gaze tracking for realistic psychological assessment.
AB  - Eye movement analysis finds tremendous usefulness in various medical screening
      applications and rehabilitation. Infrared sensor based eye trackers are becoming
      popular but these are expensive and need repeated calibration. Moreover, with
      multiple calibration also, there persists some noises called, variable and
      systematic, resulting in inaccurate gaze tracking. This study aims to build an
      one time calibration module to avoid the overhead of multiple calibration and to
      design an algorithm to remove both the types of errors effectively. The proposed
      approach is used for correcting the gaze tracking data for Digit Gazing task and
      standard recall-recognition test, where an accuracy of 90% and 82% are achieved
      respectively for detecting the gaze positions against the raw eye gaze data.
      Results also show that it is possible to perform accurate gaze tracking with one
      time calibration method provided the experimental setup is not altered.

PMID- 29059981
TI  - Towards precise tracking of electric-mechanical cardiac time intervals through
      joint ECG and BCG sensing and signal processing.
AB  - Automatic tracking of intra-beat cardiac activities in ballistocardiogram (BCG)
      is a highly interesting yet technically challenging topic for cardiac monitoring,
      due to the signal's high susceptibility to various forms of distortions. In this
      paper, we aim to further investigate the BCG waveform detection from a signal
      processing and analysis viewpoint. We collect synchronized
      electrocardiography(ECG) and BCG recordings from four healthy human subjects
      using an in-house built multi-physiological monitoring device. Particularly, we
      study post-exercise ECG-BCG signals that embed considerable variation in the
      heart beat during the post-exercise recovery phase. Furthermore, we develop an
      efficient and interactive tool for detecting and marking ECG-BCG waveforms in
      each heart beat. Through analyzing the detected time interval signals, we explore
      new interesting patterns of dynamic associations between different time interval
      signals. At the same time, we call for development of improved detection
      algorithms to address robustness and accuracy issues.

PMID- 29059982
TI  - Ambulatory gastric mucosal slow wave recording for chronic experimental studies.
AB  - Dysrhythmic bioelectric slow wave activity have been implicated in major
      functional motility disorders such as gastroparesis and chronic unexplained
      nausea and vomiting, but its correlation to symptoms is still unclear. For
      patients with severe gastroparesis, high-frequency gastric stimulation is offered
      as a therapy in some centers. Temporary gastric electrical stimulation has also
      been proposed an approach to screen patients who would benefit from the
      implantation of a permanent stimulator. In this study we introduced novel methods
      for recording slow wave activity from the gastric mucosa during the entire
      temporary stimulation phase of 5 days, in 3 patients. An ambulatory recording
      system was applied to record 3 channels of mucosal slow wave activity, as well as
      three axis accelerometer data to monitor when the patient was mobile. Techniques
      were developed to detect large movements and these time periods were excluded
      from analyses of mucosal slow waves. The frequency and amplitude of the slow
      waves was calculated in a 5 min segment, with 75% overlap, for the entire
      duration. In feasibility studies, the slow wave frequency and amplitude for the
      patients were 3.0+/-0.96 cpm and 1.43+/-1.75 mV. Large variations in slow wave
      amplitude were seen in comparsion to slow wave frequency, which were concordant
      with previous studies. The use of the ambulatory system will allow for
      investigation of pathophysiology, correlation of electrophysiology data to
      patient symptoms and to determine the effects of post-prandial and noctural slow
      wave patterns. We anticipate that future use of slow wave information alongside
      patient symptoms may allow improved selection of patients for stimulaton
      techniques.

PMID- 29059983
TI  - Ex vivo animal-model assessment of a non-invasive system for loss of resistance
      detection during epidural blockade.
AB  - During recent decades epidural analgesia has gained widespread recognition in
      many applications. In this complex procedure, anaesthetist uses a specific needle
      to inject anesthetic into the epidural space. It is crucial the appropriate
      insertion of the needle through inhomogeneous tissues placed between the skin and
      the epidural space to minimize anesthetic-related complications (e.g., nausea,
      headache, and dural puncture). Usually, anaesthetists perform the procedure
      without any supporting tools, and stop pushing the syringe when they sense a loss
      of resistance (LOR). This phenomenon is caused by the physical properties of the
      epidural space: the needle breaks the ligamentum flavum and reaches the epidural
      space, in this stage the anaesthetist perceives a LOR because the epidural space
      is much softer than the ligamentum flavum. To support the clinician in this
      maneuver we designed a non-invasive system able to detect the LOR by measuring
      the pressure exerted on the syringe plunger to push the needle up to the epidural
      space. In a previous work we described the system and its assessment during in
      vitro tests. This work aims at assessing the feasibility of the system for LOR
      detection on a more realistic model (ex vivo pig model). The system was assessed
      by analyzing: its ability to hold a constant value (saturation condition) during
      the insertion of the needle, and its ability to detect the entrance within the
      epidural space by a decrease of the system's output. Lastly, the anaesthetist was
      asked to assess how the ex vivo procedure mimics a clinical scenario. The system
      reached the saturation condition during the needle insertion; this feature is
      critical to avoid false positive during the procedure. However, it was not easy
      to detect the entrance within the epidural space due to its small volume in the
      animal model. Lastly, the practitioner found real the model, and performed the
      procedures in a conventional manner because the system did not influence his
      actions.

PMID- 29059984
TI  - Overnight non-contact continuous vital signs monitoring using an intelligent
      automatic beam-steering Doppler sensor at 2.4 GHz.
AB  - Doppler-based non-contact vital signs (NCVS) sensors can monitor heart rates,
      respiration rates, and motions of patients without physically touching them. We
      have developed a novel single-board Doppler-based phased-array antenna NCVS
      biosensor system that can perform robust overnight continuous NCVS monitoring
      with intelligent automatic subject tracking and optimal beam steering algorithms.
      Our NCVS sensor achieved overnight continuous vital signs monitoring with an
      impressive heart-rate monitoring accuracy of over 94% (i.e., within +/-5 Beats
      Per-Minute vs. a reference sensor), analyzed from over 400,000 data points
      collected during each overnight monitoring period of ~ 6 hours at a distance of
      1.75 meters. The data suggests our intelligent phased-array NCVS sensor can be
      very attractive for continuous monitoring of low-acuity patients.

PMID- 29059985
TI  - Permanency analysis on human electroencephalogram signals for pervasive Brain
      Computer Interface systems.
AB  - Brain-Computer Interface (BCI) systems use some permanent features of brain
      signals to recognize their corresponding cognitive states with high accuracy.
      However, these features are not perfectly permanent, and BCI system should be
      continuously trained over time, which is tedious and time consuming. Thus,
      analyzing the permanency of signal features is essential in determining how often
      to repeat training. In this paper, we monitor electroencephalogram (EEG) signals,
      and analyze their behavior through continuous and relatively long period of time.
      In our experiment, we record EEG signals corresponding to rest state (eyes open
      and closed) from one subject everyday, for three and a half months. The results
      show that signal features such as auto-regression coefficients remain permanent
      through time, while others such as power spectral density specifically in 5-7 Hz
      frequency band are not permanent. In addition, eyes open EEG data shows more
      permanency than eyes closed data.

PMID- 29059986
TI  - Energy efficient LoRa GPS tracker for dementia patients.
AB  - Continuous GPS tracking devices always suffer short battery life when used by
      caregivers to reduce the risk of wandering to dangerous areas by dementia
      patients. Currently the best existing tracker for dementia patients on the market
      only supports less than 10 hours battery life with a gigantic battery. It not
      only requires daily battery charging from patients/caregivers, but also becomes a
      very restrictive device. In this paper we inspected individual energy consumption
      of the components in a GPS tracker and proposed a novel energy efficient, small
      wristband by integrating the latest LoRa communication and GPS duty cycling
      technologies. We verify our prototype's communication distance and energy
      efficiency through extensive experiments in the real world. Our model and data
      show the GPS wristband is able to support up to 40 hours continuous GPS tracking
      with a frequent 60 seconds location update rate. Its range also spans 3km,
      effectively monitoring patient locations.

PMID- 29059987
TI  - Charge pumping with finger capacitance for body sensor energy harvesting.
AB  - Sensors are becoming ubiquitous and increasingly integrated with and on the human
      body; powering such "body network" devices remains an outstanding problem. In
      this paper, we demonstrate a touch interrogation powered energy harvesting
      system. This system transforms the kinetic energy of a human finger to electric
      energy, with each tap producing approximately 1 nJ of energy at a storage
      capacitor. As is well known for touch display devices, the proximity of a finger
      can alter the effective value of small capacitances; we demonstrate that these
      capacitance changes can drive a current which is rectified to charge a capacitor.
      As a demonstration, an untethered circuit charged this way can deliver enough
      instantaneous power to light a red LED every ~ 10 seconds. This technology
      illustrates the ability to communicate with and operate low-power sensors with
      motions already used for interfacing to devices.

PMID- 29059988
TI  - Polypyrrole RVC biofuel cells for powering medical implants.
AB  - Batteries for implanted medical devices such as pacemakers typically require
      surgical replacement every 5 to 10 years causing stress to the patient and their
      families. A Biofuel cell uses two electrodes with enzymes embedded to convert
      sugar into electricity. To evaluate the power producing capabilities of biofuel
      cells to replace battery technology, polypyrrole electrodes were fabricated by
      compression with Glucose oxidase and Laccase. Vitreous carbon was added to
      increase the conductivity, whilst glutaraldehyde acted as a crosslinking
      molecule. A maximum open circuit potential of 558.7 mV, short circuit current of
      1.09 mA and maximum power of 0.127 mW was obtained from the fuel cells. This was
      able to turn on a medical thermometer through a TI BQ25504 energy harvesting
      circuit, hence showing the powering potential for biomedical devices.

PMID- 29059989
TI  - Development of a wearable support system to aid the visually impaired in
      independent mobilization and navigation.
AB  - Visually impaired individuals have great difficulty in navigating unfamiliar
      environments. Conventional methods of obstacle detection are not always
      sufficient, thus a need exists for a low-cost device which could aid the visually
      impaired in navigating indoor environments. The aim of this study is to develop a
      wearable prototype support system which aids the visually impaired in independent
      navigation and mobilization. It utilizes ultrasonic sensors to detect obstacles
      and transmits feedback to the user through an array of vibration motors. The
      prototype device was evaluated by detecting the sensor signatures of various
      common static household obstacles. Trends were identified in these signatures
      which can be used to give feedback to the user of the type of obstacle
      encountered. The results show the basic feasibility of the device in static
      indoor obstacle detection and identification for the visually impaired. However,
      further refinement is needed to extend the system's functionality by detecting
      dynamic obstacles.

PMID- 29059990
TI  - Application of infrared scanning of the neck muscles to control a cursor in Human
      Computer Interface.
AB  - The feasibility of using infrared (IR) spectroscopy of the neck muscles in
      controlling a cursor in a 2-dimensional screen was assessed. The proposed
      technique utilizes two IR photoplethysmography sensors (lambda = 940nm) to
      monitor the morphological changes of the Scalene and Sternocleidomastoid muscles.
      Since the reflection of the light has valuable information about the type of
      contraction, the direction of the movement (right/left, up/down) can be simply
      derived using two sensors. A MATLAB platform was developed in which a cursor
      moves using the recorded signal. Three scenarios of high/low sensitivity and
      joystick mode were tested. The results from 4 different healthy subjects shows
      the feasibility of control in terms of throughput, overshoot, and path
      efficiency.

PMID- 29059991
TI  - An MRI-compatible force sensor for measuring differential isometric precision
      grip force.
AB  - Investigating neural correlates of fine motor control in a magnetically sensitive
      environment requires special considerations in sensor design. Our application
      requires measurement of forefinger and thumb forces during precision grip in a
      relatively low (<; 20 N) force range. This work describes the design,
      characterization and performance evaluation of an MR-compatible precision grip
      sensor that independently measures forefinger and thumb forces. We selective
      laser sintered Nylon 12 into a flexure, measuring deformation using optic fibers
      which matches our finite element model simulation. We found that the device was
      capable of measuring forces within the desired range, with some hysteresis at
      higher frequencies as expected. We conclude that the device performs well
      compared to specifications.

PMID- 29059992
TI  - Using point cloud data to improve three dimensional gaze estimation.
AB  - This paper addresses the problem of estimating gaze location in the 3D
      environment using a remote eye tracker. Instead of relying only on data provided
      by the eye tracker, we investigate how to integrate gaze direction with the point
      cloud-based representation of the scene provided by a Kinect sensor. The
      algorithm first combines the gaze vectors for the two eyes provided by the eye
      tracker into a single gaze vector emanating from a point in between the two eyes.
      The gaze target in the three dimensional environment is then identified by
      finding the point in the 3D point cloud that is closest to the gaze vector. Our
      experimental results demonstrate that the estimate of the gaze target location
      provided by this method is significantly better than that provided when
      considering gaze information alone. It is also better than two other methods for
      integrating point cloud information: (1) finding the 3D point closest to the gaze
      location as estimated by triangulating the gaze vectors from the two eyes, and
      (2) finding the 3D point with smallest average distance to the two gaze vectors
      considered individually. The proposed method has an average error of 1.7 cm in a
      workspace of 25 * 23 * 24 cm located at a distance of 60 cm from the user.

PMID- 29059993
TI  - Efficient color correction method for smartphone camera-based health monitoring
      application.
AB  - Smartphone health monitoring applications are recently highlighted due to the
      rapid development of hardware and software performance of smartphones. However,
      color characteristics of images captured by different smartphone models are
      dissimilar each other and this difference may give non-identical health
      monitoring results when the smartphone health monitoring applications monitor
      physiological information using their embedded smartphone cameras. In this paper,
      we investigate the differences in color properties of the captured images from
      different smartphone models and apply a color correction method to adjust
      dissimilar color values obtained from different smartphone cameras. Experimental
      results show that the color corrected images using the correction method provide
      much smaller color intensity errors compared to the images without correction.
      These results can be applied to enhance the consistency of smartphone camera
      based health monitoring applications by reducing color intensity errors among the
      images obtained from different smartphones.

PMID- 29059994
TI  - Quantification assessment of bradykinesia in Parkinson's disease based on a
      wearable device.
AB  - Bradykinesia is one of the primary characteristic symptoms of Parkinson's disease
      (PD). Ten-second whole-hand-grasps action was chosen to assess bradykinesia
      severity in this study. A quantification assessment system based on a self
      developed wearable device was proposed to assess the severity of the parkinsonian
      bradykinesia. The proposed assessment method used an attitude-estimation
      algorithm to extract the parkinsonian bradykinesia parameters. A regression model
      was adopted to fit the characteristic parameters with the clinical UPDRS ratings
      judged by neurologists. Clinical experiment with 15 PD patients and 5 age-matched
      healthy controls demonstrated that the predicted bradykinesia scores by proposed
      model correlated well with the judgments of neurologists (r2=0.99). The proposed
      quantification model demonstrated the greater goodness-of-fit compared with the
      related works.

PMID- 29059995
TI  - Recovery of forearm occluded trajectory in Kinect using a wrist-mounted Inertial
      Measurement Unit.
AB  - Kinect sensor is a successful device that lets 3D human motion capture be used in
      a general residential setting. This work aims to fulfill some missing
      capabilities in Kinect, which are forearm orientation estimation and forearm
      tracking in occlusion. By using a wrist-mounted Inertial Measurement Unit and
      Kinect's built-in skeleton tracking, we have developed a fusion procedure that
      improves the upper limb motion tracking without adding too many obtrusive devices
      to the user.

PMID- 29059996
TI  - Effect of electrode material on the sensitivity of interdigitated electrodes used
      for Electrical Cell-Substrate Impedance Sensing technology.
AB  - This study explores the effect of the electrode material on the sensitivity of
      interdigitated electrodes (IDEs) used in Electrical Cell-Substrate Impedance
      Sensing (ECIS) technology. This technique is a label-free method to evaluate
      cellular activity of adherent cells. IDEs of gold (Au), indium tin oxide (ITO)
      and ITO functionalized with iridium oxide (IrOx) were characterized with
      impedance spectroscopy and their interfacial impedances were evaluated in
      potassium chloride (KCl) solutions. In parallel, ECIS measurements were performed
      on these three electrode materials during the proliferation of the human breast
      cancer cell line, MCF-7. The results indicate that the difference in sensitivity
      to MCF-7 of the three materials might be strongly correlated to their interfacial
      impedances. We found that ITO electrodes coated with IrOx show slightly higher
      sensitivity to MCF-7 breast cancer cells while still offering transparency
      compared to gold, which is considered the conventional material in ECIS devices.

PMID- 29059997
TI  - The SPLENDID chewing detection challenge.
AB  - Monitoring of eating behavior using wearable technology is receiving increased
      attention, driven by the recent advances in wearable devices and mobile phones.
      One particularly interesting aspect of eating behavior is the monitoring of
      chewing activity and eating occurrences. There are several chewing sensor types
      and chewing detection algorithms proposed in the bibliography, however no
      datasets are publicly available to facilitate evaluation and further research. In
      this paper, we present a multi-modal dataset of over 60 hours of recordings from
      14 participants in semi-free living conditions, collected in the context of the
      SPLENDID project. The dataset includes raw signals from a photoplethysmography
      (PPG) sensor and a 3D accelerometer, and a set of extracted features from audio
      recordings; detailed annotations and ground truth are also provided both at
      eating event level and at individual chew level. We also provide a baseline
      evaluation method, and introduce the "challenge" of improving the baseline
      chewing detection algorithms. The dataset can be downloaded from http:
      //dx.doi.org/10.17026/dans-zxw-v8gy, and supplementary code can be downloaded
      from https://github. com/mug-auth/chewing-detection-challenge.git.

PMID- 29059998
TI  - Wireless chest wearable vital sign monitoring platform for hypertension.
AB  - Hypertension, a silent killer, is the biggest challenge of the 21st century in
      public health agencies worldwide [1]. World Health Organization (WHO) statistic
      shows that the mortality rate of hypertension is 9.4 million per year and causes
      55.3% of total deaths in cardiovascular (CV) patients [2]. Early detection and
      prevention of hypertension can significantly reduce the CV mortality. We are
      presenting a wireless chest wearable vital sign monitoring platform. It measures
      Electrocardiogram (ECG), Photoplethsmogram (PPG) and Ballistocardiogram (BCG)
      signals and sends data over Bluetooth low energy (BLE) to mobile phone-acts as a
      gateway. A custom android application relays the data to thingspeak server where
      MATLAB based offline analysis estimates the blood pressure. A server reacts on
      the health of subject to friends & family on the social media - twitter. The
      chest provides a natural position for the sensor to capture legitimate signals
      for hypertension condition. We have done a clinical technical evaluation of
      prototypes on 11 normotensive subjects, 9 males 2 females.

PMID- 29059999
TI  - Performance of compressive sensing for the reconstruction of different QRS pulses
      in ECG signals.
AB  - Compressive sensing (CS) is studied for the acquisition of different QRS
      complexes in ECG signals. By applying sparse binary measurement matrix and by
      applying regularization for promoting temporal correlation, performance of CS
      techniques for the reconstruction of ECG segments containing different QRS
      complexes, such as, normal QRS, paced QRS, right bundle branch block beat, left
      bundle branch block beat, and ventricular flutter beat, has been studied.
      Simulation results demonstrate that performance of CS differs with the types of
      beats, and ECG segments with well-known beats can be reconstructed with signal-to
      noise ratio (SNR) approximately equal to 25dB for the realization of CS systems
      with compression ratio as high as 95%; for lower compression ratio much higher
      SNR can be attained.

PMID- 29060000
TI  - Respiratory rate measurements via Doppler radar for health monitoring
      applications.
AB  - This paper presents experimental results for measuring respiratory rate using non
      contact and low power system for health-monitoring applications. The system is
      based on a Doppler effect. A mechanical setup with controllable movement
      frequency and displacement was built to mimic the human chest movements while
      breathing. A Doppler radar system was used to measure the frequency of the
      proposed system. Three different antennas were used to study the effect of
      antenna radiation pattern, gain, and cross-polarization on the accuracy of the
      measurements. An error analysis was conducted for different frequencies and
      displacements. Results demonstrated that the antenna of a moderate directivity
      and gain values, and of the least cross-polarization components has higher
      accuracy compared to other proposed antennas. It can be concluded that with a
      good selection of antenna it is possible to measure respiratory rate with a small
      error using the proposed radar system.

PMID- 29060001
TI  - Development of wearable muscle fatigue detection system using capacitance
      coupling electrodes.
AB  - Bio-information is important to confirm the body condition. Especially, the
      muscle fatigue is related to injury or decrease of concentration. Therefore, it
      is required to evaluate muscle fatigue to make subject enjoy sports. In previous
      study, muscle fatigue is evaluated by using electromyogram (EMG). However, the
      electrode for EMG measurement is generally used for contact manor. The electrodes
      are disposable and it might cause the irritation of skin. Therefore, it isn't
      fitted for measurement of muscle fatigue. We developed wearable muscle fatigue
      detection system using capacitance coupling electrodes. Developed system isn't
      caused the irritation by electrodes and can reuse it. We compared the
      conventional system using disposable electrode system and our system to evaluate
      performance. We evaluated muscle fatigue from electromyogram before and after
      futsal. An integrated electromyogram and an intermediate frequency were used for
      the evaluation of muscle fatigue. As a result, half of subjects showed tendency
      of muscle fatigue. Therefore, we showed the possibility as muscle fatigue
      detection system using the capacity coupling electrodes.

PMID- 29060002
TI  - A tracking algorithm for cell motility assays in CMOS systems.
AB  - This work proposes a method for the study and real-time monitoring of a single
      cell on a 2D electrode matrix, of great interest in cell motility assays and in
      the characterization of cancer cell metastasis. A CMOS system proposal for cell
      location based on occupation maps data generated from Electrical Cell-substrate
      Impedance Spectroscopy (ECIS) has been developed. From experimental assays data,
      an algorithm based on the analysis of the eight nearest neighbours has been
      implemented to find the cell center of mass. The path followed by a cell,
      proposing a Brownian route, has been simulated with the proposed algorithm. The
      presented results give an accuracy over 95% in the determination of the
      coordinates (x, y) from the expected cell center of mass.

PMID- 29060003
TI  - Proof of concept Laplacian estimate derived for noninvasive tripolar concentric
      ring electrode with incorporated radius of the central disc and the widths of the
      concentric rings.
AB  - Tripolar concentric ring electrodes are showing great promise in a range of
      applications including braincomputer interface and seizure onset detection due to
      their superiority to conventional disc electrodes, in particular, in accuracy of
      surface Laplacian estimation. Recently, we proposed a general approach to
      estimation of the Laplacian for an (n + 1)-polar electrode with n rings using the
      (4n + 1)-point method for n >= 2 that allows cancellation of all the truncation
      terms up to the order of 2n. This approach has been used to introduce novel
      multipolar and variable inter-ring distances concentric ring electrode
      configurations verified using finite element method. The obtained results suggest
      their potential to improve Laplacian estimation compared to currently used
      constant interring distances tripolar concentric ring electrodes. One of the main
      limitations of the proposed (4n + 1)-point method is that the radius of the
      central disc and the widths of the concentric rings are not included and
      therefore cannot be optimized. This study incorporates these two parameters by
      representing the central disc and both concentric rings as clusters of points
      with specific radius and widths respectively as opposed to the currently used
      single point and concentric circles. A proof of concept Laplacian estimate is
      derived for a tripolar concentric ring electrode with non-negligible radius of
      the central disc and non-negligible widths of the concentric rings clearly
      demonstrating how both of these parameters can be incorporated into the (4n + 1)
      point method.

PMID- 29060004
TI  - Non-invasive sensor based automated smoking activity detection.
AB  - Although smoking prevalence is declining in many countries, smoking related
      health problems still leads the preventable causes of death in the world. Several
      smoking intervention mechanisms have been introduced to help smoking cessation.
      However, these methods are inefficient since they lack in providing real time
      personalized intervention messages to the smoking addicted users. To address this
      challenge, the first step is to build an automated smoking behavior detection
      system. In this study, we propose an accelerometer sensor based non-invasive and
      automated framework for smoking behavior detection. We built a prototype device
      to collect data from several participants performing smoking and other five
      confounding activities. We used three different classifiers to compare activity
      detection performance using the extracted features from accelerometer data. Our
      evaluation demonstrates that the proposed approach is able to classify smoking
      activity among the confounding activities with high accuracy. The proposed system
      shows the potential for developing a real time automated smoking activity
      detection and intervention framework.

PMID- 29060006
TI  - Home-based upper extremity rehabilitation support using a contactless ultrasonic
      sensor.
AB  - Home-based rehabilitation protocols have been shown to improve outcomes amongst
      individuals with limited upper-extremity (UE) functionality. While approaches
      employing both video conferencing technologies and gaming platforms have been
      successfully demonstrated for such applications, concerns regarding patient
      privacy and technological complexity may limit further adoption. As an
      alternative solution for assessing adherence to prescribed UE rehabilitation
      protocols, the Echolocation Activity Detector, a linear array of first-reflection
      ultrasonic distance sensors, is proposed herein. To demonstrate its utility for
      home-based rehabilitation, a controlled experiment exploring the ability of the
      system to distinguish between various parameters of UE motion, including motion
      plane, range, and speed, was conducted for five participants. Activity
      classification is accomplished using a quadratic support vector machine
      classifier using time-domain features which exploit the known geometric
      relationships between the patient and the device, along with the ideal kinematics
      of the activities of interest. Average classification accuracy for the five
      classes of UE motion considered herein exceeds 91%.

PMID- 29060005
TI  - Rich context information for just-in-time adaptive intervention promoting
      physical activity.
AB  - Sedentary lifestyle and inadequate levels of physical activity represent two
      serious health risk factors. Nevertheless, within developed countries, 60% of
      people aged over 60 are deemed to be sedentary. Consequently, interest in
      behavior change to promote physical activity is increasing. In particular, the
      role of emerging mobile apps to facilitate behavior change has shown promising
      results. Smart technologies can help in providing rich context information
      including an objective assessment of the level of physical activity and
      information on the emotional and physiological state of the person. Collectively,
      this can be used to develop innovative persuasive solutions for adaptive behavior
      change. Such solutions offer potential in reducing levels of sedentary behavior.
      This work presents a study exploring new ways of employing smart technologies to
      facilitate behavior change. It is achieved by means of (i) developing a knowledge
      base on sedentary behaviors and recommended physical activity guidelines, and
      (ii) a context model able to combine information on physical activity, location,
      and a user's diary to develop a context-aware virtual coach with the ability to
      select the most appropriate behavior change strategy on a case by case basis.

PMID- 29060007
TI  - MuSeSe - A multisensor armchair for unobtrusive vital sign estimation and motion
      artifact analysis.
AB  - Unobtrusive vital sign estimation with sensors integrated into objects of
      everyday living can substantially advance the field of remote monitoring. At the
      same time, motion artifacts cause severe problems and have to be dealt with.
      Here, the fusion of multimodal sensor data is a promising approach. In this
      paper, we present an armchair equipped with capacitively coupled
      electrocardiogram, two types of ballistocardiographic sensors,
      photoplethysmographic and two high-frequency impedance sensors. In addition, a
      video-based sensor for motion analysis is integrated. Using a defined motion
      protocol, the feasibility of the system is demonstrated in a self
      experimentation. Moreover, the influence of different movements on different
      modalities is analyzed. Finally, robust beat-to-beat interval estimation
      demonstrates the benefits of multimodal sensor fusion for vital sign estimation
      in the presence of motion artifacts.

PMID- 29060008
TI  - A low-power high-sensitivity analog front-end for PPG sensor.
AB  - This paper presents a low-power analog front-end (AFE) photoplethysmography (PPG)
      sensor fabricated in 0.35 MUm CMOS process. The AFE amplifies the weak
      photocurrent from the photodiode (PD) and converts it to a strong voltage at the
      output. In order to decrease the power consumption, the circuits are designed in
      subthreshold region; so the total biasing current of the AFE is 10 MU A. Since
      the large input DC photocurrent is a big issue for the PPG sensing circuit, we
      apply a DC photocurrent rejection technique by adding a DC current-cancellation
      loop to reject the large DC photocurrent up to 10 MUA. In addition, a pseudo
      resistor is used to reduce the high-pass corner frequency below 0.5 Hz and Gm-C
      filter is adapted to reject the out-of-band noise higher than 16 Hz. For the
      whole sensor, the amplifier chain can achieve a total gain of 140 dBMU and an
      input integrated noise current of 68.87 pArms up to 16 Hz.

PMID- 29060009
TI  - Ultrasonic thermal dust: A method to monitor deep tissue temperature profiles.
AB  - We demonstrate a tetherless, sub-millimeter implantable temperature sensing
      system employing ultrasonic powering and ultrasonic backscatter modulation
      assembled using commercially available components. We demonstrate two sizes of
      sensors based on available components with volumes of 1.45 mm3 and 0.118 mm3.
      Individual sensors are able to resolve +/-0.5 degrees C changes in temperature,
      suitable for medical diagnostic and monitoring purposes. We verify less than 0.3
      degrees C drift in temperature readings over 14 days in physiological conditions.
      This approach is compatible with more sophisticated temperature sensors such as
      classic proportional to absolute temperature (PTAT) integrated circuits, as well
      as digital backscatter approaches. Our goal is to solve a long-standing issue:
      chronic and tetherlessly monitoring deep tissue temperature with high spatial
      accuracy.

PMID- 29060010
TI  - A ROIC for Mn(TPP)Cl-DOP-THF-Polyhema PVC membrane modified n-channel Si3N4 ISFET
      sensitive to histamine.
AB  - Intolerance of histamine could lead to scombroid poisoning with fatal
      consequences. Current detection methods for histamine are wet laboratory
      techniques which employ expensive equipment that depends on skills of seasoned
      technicians and produces delayed test analysis result. Previous works from our
      group has established that ISFETs can be adapted for detecting histamine with the
      use of a novel membrane. However, work to integrate ISFETs with a readout
      interfacing circuit (ROIC) circuit to display the histamine concentration has not
      been reported so far. This paper concerns the development of a ROIC specifically
      to integrate with a Mn(TPP)Cl-DOP-THF-Polyhema PVC membrane modified n-channel
      Si3N4 ISFET to display the histamine concentration. It embodies the design of
      constant voltage constant current (CVCC) circuit, amplification circuit and micro
      controller based display circuit. A DC millivolt source is used to substitute the
      membrane modified ISFET as preliminary work. Input is histamine concentration
      corresponding to the safety level designated by the Food and Drugs Administration
      (FDA). Results show the CVCC circuit makes the output follows the input and keeps
      VDS constant. The amplification circuit amplifies the output from the CVCC
      circuit to the range 2.406-4.888V to integrate with the microcontroller, which is
      programmed to classify and display the histamine safety level and its
      corresponding voltage on a LCD panel. The ROIC could be used to produce direct
      output voltages corresponding to histamine concentrations, for in-situ
      applications.

PMID- 29060011
TI  - Novel carbon fiber probe for temperature monitoring during thermal therapies.
AB  - Thermal treatments are a valid clinical option in the management of several solid
      tumors. The difficulties to perform an accurate prediction improve the
      selectivity of the treatment effects represent the main hurdles in the spread of
      these techniques. Among other solutions, thermometric techniques are gaining
      acceptance in monitoring the effects of thermal treatments because they provide a
      clear end-point to obtain the complete removal of cancer without damaging the
      surrounding healthy tissue. This paper proposes a custom needle-like probe made
      of carbon fibers to embed seven fiber Bragg grating (FBG) sensors. This tool aims
      at a multiple points monitoring the tissue temperature during the thermal
      procedures, streamlining the FBG sensors insertion within the organ. After the
      description of the probe manufacturing, we reported the calibration of the seven
      sensors embedded within the probe, their step response, and the feasibility
      assessment of the probe for temperature monitoring during laser ablation on
      animal model (both in vivo and ex vivo). Results show that the proposed probe is
      easily maneuverable by the clinician, the sensors have a linear response with the
      temperature and a short step response; moreover, the probe allows measuring the
      temperature in seven points of the tissue; finally, it can be used during CTand
      MR-guided procedures without causing any artifact to the images. Thanks to these
      features the probe may be an useful solution to improve the safety and the
      outcomes of minimally invasive thermal ablation procedures, so to spread these
      procedures in the clinical field.

PMID- 29060012
TI  - Pulse oximetry in the neck - a proof of concept.
AB  - Oxygen saturation levels are routinely monitored in clinical settings. Pulse
      oximetry, in transmittance operation mode, is the most common method of
      estimating oxygen saturation (SpO2). This is inexpensive and non-invasive and
      thus allows for long-term monitoring. However, it suffers from issues such as
      signal integrity, reliability and patient comfortability. As a result, there is
      an interest in exploring other locations on the body where oxygen saturation can
      be measured reliably. In this paper, a wearable device has been designed to study
      the feasibility of extracting photoplethysmogram (PPG) signals at the neck in
      reflectance pulse oximetry mode. It explores the signal integrity and strength
      compared to other locations as well as the presence of motion artefacts in that
      location. The results demonstrate that the PPG signals acquired at the neck show
      a very strong correlation (r=0.82) with the SpO2 values obtained using a
      commercial device. Further, the SpO2 values are calculated with an accuracy of
      98.6%.

PMID- 29060013
TI  - Temperature influence on the response at low airflow of a variable orifice
      flowmeter.
AB  - In mechanical ventilation, in particular when neonates are ventilated, it is
      crucial to accurately control the amount of the gas delivered to the patients.
      Mechanical ventilators are equipped with one of more flowmeters. The signal of
      the flowmeter is used as feedback to control the amount of gas delivered to the
      patients. Therefore, the accuracy of the flowmeter plays a crucial role in the
      accurate adjustment of the gas amount delivered by the ventilator. Among several
      solutions, variable area orifice meters (VAOMs) have several valuable features
      (e.g., good accuracy, and adequate frequency response), moreover they have the
      main advantage, with respect to orifice meters, related to the linearity of the
      response. Despite of their spread in this field, there are not studies focused on
      the analysis of the air temperature influence on VAOMs response. This study
      focuses on this topic by investigating the gas temperature influence on the
      response of a commercial VAOM. Experiments have been performed at low airflow (up
      to 1.5 L.min-1) and at four different temperatures (i.e., from 22 degrees C to 38
      degrees C) covering the range of interest in the field of artificial ventilation.
      Results show that the response of the VAOM under test is sensitive to
      temperature: at constant airflow the higher the temperature the higher the sensor
      output. This analysis may be useful to add correction to sensor output in order
      to reject the influence of temperature, so to minimize the measurement error due
      to this factor.

PMID- 29060014
TI  - Functionalized electromagnetic actuation method for aggregated nanoparticles
      steering.
AB  - Despite the promising results in magnetic nanoparticles (MNPs) based targeted
      drug delivery (TDD), the aggregation of the magnetic nanoparticles deteriorates
      targeting performance. This paper aims to introduce a magnetic actuation function
      for aggregated nanoparticles steering in vascular network. To improve the drug
      delivery performance, first the governing dynamics has been introduced, next the
      modified field function (MFF) concept has been proposed and finally a
      computational platform for a Y-shape channel has been used to simulate the
      particles steering performance. The results showed an acceptable agreement with
      the experimental results. The proposed actuation method enables us to more
      accurately steer aggregated nanoparticles and improves targeting performance.

PMID- 29060015
TI  - Dynamic electromechanical control of biomolecules using a nano virtual cathode
      display.
AB  - The dynamic electromechanical control of spatial structures of biomolecules in
      aqueous solutions was demonstrated using a nano virtual cathode display. By
      generating a focused electric field around the biomolecules using an electron
      beam (EB), the molecules' spatiotemporal responses to the electrical stimuli,
      such as globule transition of DNA random coils and deformation of planar lipid
      bilayers and vesicles, were successfully observed. The proposed system may be
      applied to high resolution and high degree-of-freedom manipulations to measure
      the mechanical and structural properties of bio-nanomaterials.

PMID- 29060016
TI  - Development and testing of a new cognitive technological tool for episodic
      memory: A feasibility study.
AB  - Cognitive Rehabilitation Therapy refers to any systemic therapy specifically
      designed to enhance cognitive performance. Recent studies have shown that
      physical exercise is beneficial for cognitive activity in patients with
      degenerative diseases. Therefore, the objective of the present study is to
      provide training for cognitive functions that take advantage of the physical
      activity in the execution of the task. A feasibility study concerning the
      application of a new bioengineering technique in cognitive rehabilitation is
      presented and it divided into two parts. The first one aims at developing a new
      cognitive tool, called SmartTapestry (ST), for motor and cognitive
      rehabilitation. The second part aims at understanding its technical viability and
      its level of sensitivity in measuring the same cognitive domains covered by the
      standardized tests. The hypothesis of this study is that, despite the
      introduction of this new variable, the proposed system has the same sensitivity
      of the traditional tests. The results suggest a good correlation between the two
      approaches and that SmartTapestry can train the same cognitive functions of
      traditional cognitive tasks.

PMID- 29060017
TI  - Feasibility study on the assessment of auditory sustained attention through
      walking motor parameters in mild cognitive impairments and healthy subjects.
AB  - Dementia and other cognitive disorders affect more than 35 million people
      worldwide. Over the last years, cognitive training tools were used to improve the
      brain functioning, thus to slow down the cognitive decline. Recently, research
      studies have demonstrated that aerobic exercise could play an important
      restorative role toward cognitive impairments. Therefore, the aim of this work is
      to present an innovative sensorized approach which combines aerobic exercise and
      traditional cognitive tools for daily training.

PMID- 29060018
TI  - Modeling and analysis of individual with lower extremity amputation locomotion
      using prosthetic feet and running-specific prostheses.
AB  - Prostheses have enabled individuals with lower extremity amputation (ILEAs) to
      accomplish many daily activities. Prosthetic feet allow ILEA to locomote and
      improves their quality of life. Carbon-fiber running-specific prostheses (RSPs)
      with energy storing capabilities support ILEAs to perform sprinting by partly
      providing spring-like properties in their amputated legs. Previous studies
      declare the spring-like RSP behavior and stiffness regulation during ILEA
      sprinting using RSP, though little is known about the behavior of the whole
      system that is a complex combination of human body and prostheses. This paper
      models this combined system with human and prosthetic foot and RSP using the
      digital human technology, then, analyzes the ILEA walking using the prosthetic
      foot and sprinting using RSP. We develop models that are combinations of human
      and prostheses by individualizing a linkage structure and inertial parameters of
      the digital human model. Then, locomotion of ILEA is analyzed based on
      measurements with optical motion capture system and force plates, and kinematics
      and dynamics computation. This modeling and computational technique can be
      applied to the locomotion of ILEA as well as a human motion using tools, and
      expanded to an analysis and improvement of system involving human.

PMID- 29060019
TI  - A multimodal interface to resolve the Midas-Touch problem in gaze controlled
      wheelchair.
AB  - Human-computer interaction (HCI) research has been playing an essential role in
      the field of rehabilitation. The usability of the gaze controlled powered
      wheelchair is limited due to Midas-Touch problem. In this work, we propose a
      multimodal graphical user interface (GUI) to control a powered wheelchair that
      aims to help upper-limb mobility impaired people in daily living activities. The
      GUI was designed to include a portable and low-cost eye-tracker and a soft-switch
      wherein the wheelchair can be controlled in three different ways: 1) with a
      touchpad 2) with an eye-tracker only, and 3) eye-tracker with soft-switch. The
      interface includes nine different commands (eight directions and stop) and
      integrated within a powered wheelchair system. We evaluated the performance of
      the multimodal interface in terms of lap-completion time, the number of commands,
      and the information transfer rate (ITR) with eight healthy participants. The
      analysis of the results showed that the eye-tracker with soft-switch provides
      superior performance with an ITR of 37.77 bits/min among the three different
      conditions (p<;0.05). Thus, the proposed system provides an effective and
      economical solution to the Midas-Touch problem and extended usability for the
      large population of disabled users.

PMID- 29060020
TI  - Design, implementation and performance validation of UOMPro artificial hand:
      Towards affordable hand prostheses.
AB  - In this paper, an anthropometric, active artificial prosthetic hand named UOMPro
      (University of Moratuwa Prosthetic) is proposed. The UOMPro hand is realized
      during research on developing affordable hand prostheses for use by people mainly
      in developing countries where purchasing high cost state-of-the-art commercial
      hand prostheses may be beyond their capacity. The proposed hand is developed with
      an affordable cost (<; 850 USD) and it consists of 6 Degrees of Freedom (DOF)
      including flexion/extension motions of five fingers and abduction/adduction
      motion of the thumb finger. Under actuated fingers are fabricated using a
      combination of 3D printed parts and CNC machined aluminum which addresses
      drawbacks in fully 3D printed hands. All components of the electronic control
      circuit which are responsible for low-level controlling of the hand are placed
      inside the hand where a simple serial communication interface is provided to link
      with high-level control methods. The implemented low-level controller can
      communicate with either a high-level controller that sends individual fingers
      position commands or a high-level controller which sends hand grip pattern
      commands. A set of experiments are conducted to validate the performance of the
      overall system and results are presented with potential future directions.

PMID- 29060021
TI  - Construction of a soft wearable body cooling system for persons with spinal cord
      injury.
AB  - This paper describes the construction of a body cooling system to avoid
      heatstroke for survivors of cervical spinal cord injury. For accomplishment of
      this purpose, we chose the neck as a cooling point of the body, and we
      constructed a prototype neck cooling head with a refrigerated circulator. The
      neck cooling head was made by thin heat-welding thermoplastic films with high
      thermal conductivity. To test our proposed system, we conducted experiments on
      two unimpaired participants in a room which simulated a hot summer day (33 [
      degrees C], relative humidity 40%). Reduction of sweating were observed, and the
      average skin temperatures and the core temperature of the head with cooling
      increased more slowly than those without cooling. The estimated cooling power of
      the proposed system was about 10 [W] with 50 [W] total power consumption of the
      cooling head.

PMID- 29060022
TI  - Wireless navigation of pigeons using polymer-based fully implantable stimulator:
      A pilot study using depth electrodes.
AB  - A polymer-based implantable stimulator for wirelessly navigating pigeons was
      conceptually suggested and a pilot study using depth electrodes was conducted. In
      this study, depth electrodes based on liquid crystal polymer (LCP) with eight
      channels were designed and fabricated. Electrochemical impedance spectrum (EIS)
      assessments were performed to measure impedances of the electrodes. The average
      value of the measured impedances was 16.8?15.8  degrees  kMU. The electrodes were
      then advanced to a target nucleus (formatio reticularis medialis mesencephalic,
      FRM) of a pigeon to prove their in vivo feasibilities. Biphasic current pulses
      were generated by a custom-made stimulator and delivered to the electrodes to
      stimulate the FRM electrically. Pulses with an amplitude level of 0.567 MUA, a
      rate of 58.0 Hz, and a duration of 1.00 ms were applied with inter-stimulus
      intervals of three minutes. Turning and circling behaviors were consistently
      shown when the FRM was stimulated. The feasibilities of the electrodes were
      proved in both in vitro and in vivo tests, as a pilot study for the suggested
      scheme. Finally, several discussions of the assessments and extensions for a
      fully implantable stimulator were described.

PMID- 29060023
TI  - A novel hidden Markov model-based pattern discrimination method with the anomaly
      detection for EMG signals.
AB  - This paper proposes a novel sequential pattern recognition method enabling
      calculation of a posteriori probability for learned and unlearned classes. In
      this approach, probability density functions of unlearned classes are
      incorporated in a hiddenMarkov model to classify undefined classes via model
      parameter estimation using given learning samples. The technique can be applied
      to various pattern recognition problems such as motion classification with
      electromyogram (EMG) signals and in support for disease diagnosis. In the
      experiments conducted, motion classification from EMG signals was implemented
      with three subjects for eight learned/unlearned forearm motions. The proposed
      method produced higher levels of classification performance (learned motions:
      90.13%; unlearned motions: 91.25%) than previous approaches. The results
      demonstrated the effectiveness of the technique.

PMID- 29060024
TI  - Robust tracking of dexterous continuum robots: Fusing FBG shape sensing and
      stereo vision.
AB  - Robust and efficient tracking of continuum robots is important for improving
      patient safety during space-confined minimally invasive surgery, however, it has
      been a particularly challenging task for researchers. In this paper, we present a
      novel tracking scheme by fusing fiber Bragg grating (FBG) shape sensing and
      stereo vision to estimate the position of continuum robots. Previous visual
      tracking easily suffers from the lack of robustness and leads to failure, while
      the FBG shape sensor can only reconstruct the local shape with integral
      cumulative error. The proposed fusion is anticipated to compensate for their
      shortcomings and improve the tracking accuracy. To verify its effectiveness, the
      robots' centerline is recognized by morphology operation and reconstructed by
      stereo matching algorithm. The shape obtained by FBG sensor is transformed into
      distal tip position with respect to the camera coordinate system through
      previously calibrated registration matrices. An experimental platform was set up
      and repeated tracking experiments were carried out. The accuracy estimated by
      averaging the absolute positioning errors between shape sensing and stereo vision
      is 0.67+/-0.65 mm, 0.41+/-0.25 mm, 0.72+/-0.43 mm for x, y and z, respectively.
      Results indicate that the proposed fusion is feasible and can be used for closed
      loop control of continuum robots.

PMID- 29060025
TI  - A distributed cerebellar-inspired learning model for robotic arm control.
AB  - The cerebellum plays a big role in motor control and motor coordination in
      mammals, especially for limbs control. Therefore, many cerebellar models were
      proposed to be applied in the field of robotic arm control. However, some
      problems exist in the current cerebellar modeling approach, such as lack of the
      expression of bio-characteristics, limited learning ability et al. Therefore, a
      distributed cerebellar-inspired learning model was proposed to mimic the
      physiology and anatomy features of the cerebellum. Meanwhile, this model could
      learn to adjust the motor command according to the error information provided by
      the inferior olive to achieve control goal. To test the performance of the
      cerebellar model, a robotic arm control system was implemented. The results
      showed that our model was able to complete the robotic arm control tasks
      successfully.

PMID- 29060026
TI  - A theoretical study and implementation of spinal traction system with real-time
      biosignal feedback system.
AB  - A large number of people suffer from spinal diseases, or so called back pain.
      Although numerous medical devices and therapies have been developed for
      treatment, back illnesses remain a problematic issue. Recently, the spinal
      traction has been reported to have a positive effect on spinal diseases, and an
      intelligent machine which stimulates the spine has been developed. This paper
      presents a theoretical study of how appropriate force can be applied from the
      spinal traction system to the spine. The system is designed to stimulate the
      spine, and the scale of force is controlled by the patient's biological status,
      such as blood pressure or heart rate. The theoretical force is compared to
      experimental results, and shows that the force is highly correlated to the
      theoretical derivation. The proposed approach can be utilized to customize the
      force on the spine based on the patients' weight and the angle of the spinal
      traction machine.

PMID- 29060028
TI  - Efficacy of a knee orthosis that uses an elastic element.
AB  - In this study, we evaluate the support effect of a knee orthosis that uses the
      elasticity element from the perspective of human motor control. The speeds during
      level-ground walking and the angles during slope walking were varied during the
      experiments. It was observed that the support effect was remarkable at 4 km/h
      during the level-ground walking. In particular, at 12 degrees  during slope
      walking, the strength of the stretching muscle decreased for the knee joint in
      the stance phase and the hip joint in the swing phase. The results show that this
      orthosis exhibits a different effect from the conventional type adjustment to
      damping in the swing phase.

PMID- 29060027
TI  - Augmented marker tracking for peri-acetabular osteotomy surgery.
AB  - We developed and validated a small, easy to use and cost-effective augmented
      marker-based hybrid navigation system for peri-acetabular osteotomy (PAO)
      surgery. The hybrid system consists of a tracking unit directly placed on the
      patient's pelvis, an augmented marker with an integrated inertial measurement
      unit ('MU) attached to the patient's acetabular fragment and the host computer.
      The tracking unit sends a live video stream of the marker to the host computer
      where the marker's pose is estimated. The augmented marker with the 'MU sends its
      pose estimate to the host computer where we apply sensor fusion to compute the
      final marker pose estimate. The host computer then tracks the orientation of the
      acetabular fragment during peri-acetabular osteotomy surgery. Anatomy
      registration is done using a previously developed registration device. A Kalman
      filter-based sensor fusion was added to complete the system. A plastic bone study
      was performed for validation between an optical tracking-based navigation system
      and our proposed system. Mean absolute difference for inclination and anteversion
      was 1.63 degrees and 1.55 degrees, respectively. The results show that our system
      is able to accurately measure the orientation of the acetabular fragment.

PMID- 29060029
TI  - Design and development of platform ankle rehabilitation robot with Shape Memory
      Alloy based actuator.
AB  - Various ankle rehabilitation robots have been developed in the recent decade to
      improve ankle strength and mobility and to alleviate the burdens on clinicians
      and physiotherapists. However, existing designs have stiff actuating mechanism,
      heavy and bulky electromagnetic or pneumatic actuators. This paper introduces
      ankle rehabilitation robot that utilizes Shape Memory Alloy (SMA) wire actuator
      to provide foot plantarflexion and dorsiflexion during rehabilitation exercise.
      SMA wire is a smart material that can contract when it is heated and expand back
      to its original shape when it is cooled. It also has high power to weight ratio.
      However, the SMA wire has low cooling rate thus limits its operating frequency. A
      periodical cooling mechanism is proposed here. Its efficacy is then evaluated
      against natural cooling and continuous forced convection. The experimental study
      shows promising results and demonstrates that periodical cooling has both the
      advantages of natural cooling and forced convection and can improve the cooling
      rate of SMA wire actuator.

PMID- 29060030
TI  - Shape memory effect of nano-ferromagnetic particle doped NiTi for orthopedic
      devices and rehabilitation techniques.
AB  - This paper introduces a novel shape memory alloy (SMA) material for the
      controllability in the shape recovery of traditional SMA for orthopedic devices
      and rehabilitation techniques. The proposed material is formed by doping nano
      ferromagnetic particle into porous NiTi alloy. The finite element analysis of
      shape memory effect property of the different distribution of nano-ferromagnetic
      particle is done and compared for same load and boundary conditions. The
      comparative analysis of the percentage change in volume deformation when load is
      released (for 2nd step) shows an average of 2.55 % with standard deviation of
      1.69 whereas on thermal loading (for 3rd step) shows an average of 94.94% with
      standard deviation of 7.75 for all heterogeneous distribution of nano-particles
      in porous NiTi alloy. Our findings are, all the different conditions of
      heterogeneous distributions of nano-ferromagnetic particle doped NiTi alloy
      exhibits its inherent SME property.

PMID- 29060031
TI  - Effects of wide step walking on swing phase hip muscle forces and spatio-temporal
      gait parameters.
AB  - Human walking can be viewed essentially as a continuum of anterior balance loss
      followed by a step that re-stabilizes balance. To secure balance an extended base
      of support can be assistive but healthy young adults tend to walk with relatively
      narrower steps compared to vulnerable populations (e.g. older adults and
      patients). It was, therefore, hypothesized that wide step walking may enhance
      dynamic balance at the cost of disturbed optimum coupling of muscle functions,
      leading to additional muscle work and associated reduction of gait economy. Young
      healthy adults may select relatively narrow steps for a more efficient gait. The
      current study focused on the effects of wide step walking on hip abductor and
      adductor muscles and spatio-temporal gait parameters. To this end, lower body
      kinematic data and ground reaction forces were obtained using an Optotrak motion
      capture system and AMTI force plates, respectively, while AnyBody software was
      employed for muscle force simulation. A single step of four healthy young male
      adults was captured during preferred walking and wide step walking. Based on
      preferred walking data, two parallel lines were drawn on the walkway to indicate
      50% larger step width and participants targeted the lines with their heels as
      they walked. In addition to step width that defined walking conditions, other
      spatio-temporal gait parameters including step length, double support time and
      single support time were obtained. Average hip muscle forces during swing were
      modeled. Results showed that in wide step walking step length increased, Gluteus
      Minimus muscles were more active while Gracilis and Adductor Longus revealed
      considerably reduced forces. In conclusion, greater use of abductors and loss of
      adductor forces were found in wide step walking. Further validation is needed in
      future studies involving older adults and other pathological populations.

PMID- 29060032
TI  - Change in functional networks for transitions between states of consciousness
      during midazolam-induced sedation.
AB  - How brain dynamics change across conscious states, including reliable signatures
      of the transitions between unconsciousness and consciousness, remains unclear. In
      this work, we addressed the changes in functional brain networks during self
      titrated midazolam sedation using high-density electroencephalography (EEG) in
      ten subjects. We were particularly interested in the underlying network
      alterations, identified with graph theory, associated with transitions between
      states of consciousness. The weighted Phase Lag Index (wPLI) was used as the
      connectivity estimator between two signals. Based on wPLI, we calculated network
      properties such as characteristic path length, clustering coefficient, and small
      worldness for measuring the integration and segregation of the brain network. We
      found significant changes in power and wPLI at different levels of consciousness.
      During unconsciousness, wPLI over the parietal region was higher in the delta
      band (1-4Hz). The frontal-parietal interaction in the delta band was also
      stronger during the transition from consciousness to unconsciousness. There was
      the significant difference of wPLI over the frontal region between consciousness
      and unconsciousness in the sigma band (12-15Hz). The topological properties
      across conscious states were significantly changed in the delta band and sigma
      band. Our results showed parietal brain dynamics is associated with
      consciousness. Our data also suggest that reversible changes in delta power and
      connectivity underlie changes in conscious state.

PMID- 29060033
TI  - Neuronal activity in human anterior cingulate cortex modulates with internal
      cognitive state during multi-source interference task.
AB  - The dorsal anterior cingulate cortex (dACC) is thought to be essential for normal
      adaptation of one's behavior to difficult decisions, errors, and reinforcement.
      Here we examine single neurons from the human dACC in the context of a
      statistical model, including a cognitive state that varies with changes in
      cognitive interference induced by a Stroop-like task. We then include this
      cognitive state in point process models of single unit activity and subject
      reaction time. These results suggest that consideration of a latent cognitive
      state can explain additional variance in neural and behavioral dynamics.

PMID- 29060034
TI  - Spatial constraints of binocularly matched information on perceived depth
      resulted from temporal interocular asynchrony.
AB  - Quantitative depth of a subjective occluding surface could only be perceived when
      binocularly matched information is presented along with temporal interocular
      unmatched (IOUM) information [1]. However, it is still unclear whether the
      horizontal separation that binocularly matched information is presented from the
      occluding surface edge would affect the quantitative depth perception. In the
      present study we aim to answer this question by manipulating the distance between
      binocularly matched and IOUM information in spatial domains. In Experiment 1, we
      examined the spatial limitation of binocular matched information along horizontal
      axes by measuring the threshold for quantitatively perceiving depth from temporal
      interocular asynchrony. In Experiment 2, within the threshold, temporal IOUM
      information was presented at three distances from the matched information along
      horizontal axes, respectively. Our results from these experiments showed a robust
      effect of binocular information in generating quantitative perceived depth from
      IOUM information in spatial domains. Moreover, the perceived depth of the
      subjective surface can be significantly influenced by spatial separations along
      horizontal axes. This may help to propose a computational theory of the
      mechanisms underlying "da Vinci stereopsis" in motion and other stereoscopic
      percepts.

PMID- 29060035
TI  - An input-output linear time invariant model captures neuronal firing responses to
      external and behavioral events.
AB  - Investigating how neurons in different motor regions respond to external stimuli
      and behavioral events provides insight into motor control. A recent approach to
      studying neuronal activity is to construct a zero-input linear time invariant (ZI
      LTI) state-space model, wherein the state vector consists of firing rate signals
      for different populations of neurons across motor regions. This approach allows
      for the populations to influence each other in a dynamical manner given an
      initial firing rate condition, and the model can accurately reconstruct firing
      rates within a limited epoch in the motor task during which no event occurs.
      Here, we generalize this LTI modeling approach to characterize firing responses
      of neurons to two events (a go cue and movement onset) in a movement task with a
      non-zero input LTI state-space model, herein referred to as input-output LTI (IO
      LTI). Specifically, responses from 196 neurons in the primary motor (M1), ventral
      premotor (PMv), and dorsal premotor cortex (PMd) were recorded and modeled in two
      nonhuman primates executing a reach-to-grasp task. We found that a single IO-LTI
      model can reconstruct neuronal firing rate patterns of six populations of these
      neurons across the three areas in the presence of multiple events (go cue,
      movement onset). This is the first step towards constructing generative models of
      neuronal firing rates in the presence of multiple events, which then can be used
      to construct better decoders for brain machine interactive control.

PMID- 29060036
TI  - Localizing neuronal somata from Multi-Electrode Array in-vivo recordings using
      deep learning.
AB  - With the latest development in the design and fabrication of high-density Multi
      Electrode Arrays (MEA) for in-vivo neural recordings, the spatiotemporal
      information in the recorded signals allows for refined estimation of a neuron's
      location around the probe. In parallel, advances in computational models for
      neural activity enables simulation of recordings from neurons with detailed
      morphology. Our approach uses deep learning algorithms on a large set of such
      simulation data to extract the 3D position of the neuronal somata. Multi
      compartment models from 13 different neural morphologies in layer 5 (L5) of the
      rat's neocortex are placed at random locations and with different alignments with
      respect to the MEA. The sodium trough and repolarisation peak images on the MEA
      serve as input features for a Convolutional Neural Network (CNN), which predicts
      the neural location robustly and with low error rates. The forward
      modeling/machine learning approach yields very accurate results for the different
      morphologies and is able to cope with different neuron alignments.

PMID- 29060037
TI  - Electro-mechanical response of a 3D nerve bundle model to mechanical loads
      leading to axonal injury.
AB  - Axonal damage is one of the most common pathological features of traumatic brain
      injury, leading to abnormalities in signal propagation for nervous systems. We
      present a 3D fully coupled electro-mechanical model of a nerve bundle, made with
      the finite element software Abaqus 6.13-3. The model includes a real-time
      coupling, modulated threshold for spiking activation and independent alteration
      of the electrical properties for each 3-layer fibre within the bundle.
      Compression and tension are simulated to induce damage at the nerve membrane.
      Changes in strain, stress distribution and neural activity are investigated for
      myelinated and unmyelinated nerve fibres, by considering the cases of an intact
      and of a traumatized nerve membrane. Results show greater changes in transmitting
      action potential in the myelinated fibre.

PMID- 29060038
TI  - EEG alpha power change during working memory encoding in adults with different
      memory performance levels.
AB  - Working memory (WM) capacity affects our daily life in many ways, and its
      decrease often associates with neural disorders (e.g. Alzheimer's disease).
      Several studies have confirmed that alpha rhythms play an active role in memory
      mechanism. In the present study, we designed a digit verbal span experiment to
      find out that how the alpha power change during working memory encoding, and the
      relationship between alpha power and individual WM performance. Consistent with
      previous studies, our results confirm that alpha power is positively related to
      WM performance. Participants who had higher alpha power during WM encoding
      achieved better memory performance. We can conclude that the reason is alpha
      rhythms reflect inhibition of task-irrelevant information. Howbeit, a linear
      relationship between WM load and alpha power amplitude during memory encoding
      cannot be deduced in our experiment.

PMID- 29060039
TI  - Finger movements are mainly represented by a linear transformation of energy in
      band-specific ECoG signals.
AB  - Electrocardiogram (ECoG) recordings are very attractive for Brain Machine
      Interface (BMI) applications due to their balance between good signal to noise
      ratio and minimal invasiveness. The design of ECoG signal decoders is an open
      research area to date which requires a better understanding of the nature of
      these signals and how information is encoded in them. In this study, a linear and
      a non-linear method, Linear Regression Model (LRM) and Artificial Neural Network
      (ANN) respectively, were used to decode finger movements from energy in band
      specific ECoG signals. It is shown that the ANN only slightly outperformed the
      LRM, which suggests that finger movements are mainly represented by a linear
      transformation of energy in band-specific ECoG signals. In addition, comparing
      our results to similar Electroencephalogram (EEG) studies illustrated that the
      spatio-temporal summation of multiple neural signals is itself linearly
      correlated with movement, and is not an artifact introduced by the scalp or
      cranium. Furthermore, a new algorithm was employed to reduce the number of
      spectral features of the input signals required for either of the decoding
      methods.

PMID- 29060040
TI  - Active brainwave pattern generation for brain-to-machine communication.
AB  - Over the years of research, Electroencephalogram (EEG) signal study has grown to
      give promising outcomes. A lot of research has been done on implementing brain
      computer-interfaces, and the brain-computer interface (BCI) algorithm as well as
      the study of the effects of different stimuli on brain signals. This paper
      intends to make progress toward that goal by developing a responsive real-time
      EEG-based brain-to-machine communication system by generating distinct EEG
      signals at will and identification of the explicit pattern that they reflect for
      the presented self-induced internal visual and auditory stimuli. The brain-to
      machine communication system delivers the real-time capture, analysis, and
      visualization of the brain signal patterns that can be used for smart medical
      applications such as rehabilitation robotic control, smart wheelchair, etc.

PMID- 29060041
TI  - A sLORETA study for gaze-independent BCI speller.
AB  - EEG-based BCI (brain-computer-interface) speller, especially gaze-independent BCI
      speller, has become a hot topic in recent years. It provides direct spelling
      device by non-muscular method for people with severe motor impairments and with
      limited gaze movement. Brain needs to conduct both stimuli-driven and stimuli
      related attention in fast presented BCI paradigms for such BCI speller
      applications. Few researchers studied the mechanism of brain response to such
      fast presented BCI applications. In this study, we compared the distribution of
      brain activation in visual, auditory, and audio-visual combined stimuli paradigms
      using sLORETA (standardized low-resolution brain electromagnetic tomography).
      Between groups comparisons showed the importance of visual and auditory stimuli
      in audio-visual combined paradigm. They both contribute to the activation of
      brain regions, with visual stimuli being the predominate stimuli. Visual stimuli
      related brain region was mainly located at parietal and occipital lobe, whereas
      response in frontal-temporal lobes might be caused by auditory stimuli. These
      regions played an important role in audio-visual bimodal paradigms. These new
      findings are important for future study of ERP speller as well as the mechanism
      of fast presented stimuli.

PMID- 29060042
TI  - The effect of semantic congruence for visual-auditory bimodal stimuli.
AB  - It is commonly believed that brain has faster reaction speed and higher reaction
      accuracy on visual-auditory bimodal stimuli than single modal stimuli in current
      neuropsychological researches, while visual-auditory bimodal stimuli (VABS) do
      not show corresponding superiority in BCI system. This paper aims at
      investigating whether semantically congruent stimuli could also get better
      performance than semantically incongruent stimuli in Brain Computer Interface
      (BCI) system. Two VABS based paradigms (semantically congruent or incongruent)
      were conducted in this study. 10 healthy subjects participated in the experiment
      in order to compare the two paradigms. The results indicated that the higher
      Event-related potential (ERP) amplitude of semantic incongruent paradigm were
      observed both in target and non-target stimuli. Nevertheless, we didn't observe
      significant difference of classification accuracy between congruent and
      incongruent conditions. Most participants showed their preference on semantically
      congruent condition for less workload needed. This finding demonstrated that
      semantic congruency has positive effect on behavioral results (less workload) and
      insignificant effect on system efficiency.

PMID- 29060043
TI  - A Brain Machine Interface for command based control of a wheelchair using
      conditioning of oscillatory brain activity.
AB  - In this research a new method of wheelchair control using a Brain Computer
      Interface (BCI) is proposed, in an attempt to bridge the gap between in-lab and
      real life applications, we believe it would provide a high level control over the
      BCI instead of the normal low level commands. It is anticipated to emphasis on mu
      rhythm to provide the control signals. The wheelchair is equipped with a mapping
      system, which scans the area and provides a map containing information about the
      user's current location and next possible destinations, then provides an
      optimized list of possible trajectories to reach the destination. The paradigm
      allows users to control the interface using motor imagery and issue commands to
      switch between possible trajectories and then confirm the choice. Commands
      trigger the motion of the wheelchair to the intended destination using a user
      selected path with speed up to 0.5 m/s. The interface also allows the user to
      interact with different robots through a common robotic system. Evaluation
      results indicate that this paradigm is indeed usable and could lead to promising
      outcomes.

PMID- 29060044
TI  - A hybrid BCI web browser based on EEG and EOG signals.
AB  - In this study, we propose a new web browser based on a hybrid brain computer
      interface (BCI) combining electroencephalographic (EEG) and electrooculography
      (EOG) signals. Specifically, the user can control the horizontal movement of the
      mouse by imagining left/right hand motion, and control the vertical movement of
      the mouse, select/reject a target, or input text in an edit box by blinking eyes
      in synchrony with the flashes of the corresponding buttons on the GUI. Based on
      mouse control, target selection and text input, the user can open a web page of
      interest, select an intended target in the web and read the page content. An
      online experiment was conducted involving five healthy subjects. The experimental
      results demonstrated the effectiveness of the proposed method.

PMID- 29060045
TI  - A real-time spike sorting method based on the embedded GPU.
AB  - Microelectrode arrays with hundreds of channels have been widely used to acquire
      neuron population signals in neuroscience studies. Online spike sorting is
      becoming one of the most important challenges for high-throughput neural signal
      acquisition systems. Graphic processing unit (GPU) with high parallel computing
      capability might provide an alternative solution for increasing real-time
      computational demands on spike sorting. This study reported a method of real-time
      spike sorting through computing unified device architecture (CUDA) which was
      implemented on an embedded GPU (NVIDIA JETSON Tegra K1, TK1). The sorting
      approach is based on the principal component analysis (PCA) and K-means. By
      analyzing the parallelism of each process, the method was further optimized in
      the thread memory model of GPU. Our results showed that the GPU-based classifier
      on TK1 is 37.92 times faster than the MATLAB-based classifier on PC while their
      accuracies were the same with each other. The high-performance computing features
      of embedded GPU demonstrated in our studies suggested that the embedded GPU
      provide a promising platform for the real-time neural signal processing.

PMID- 29060046
TI  - Performance predictors of motor imagery brain-computer interface based on spatial
      abilities for upper limb rehabilitation.
AB  - Motor Imagery based BCIs (MI-BCIs) allow the control of devices and communication
      by imagining different mental tasks. Despite many years of research, BCIs are
      still not the most accurate systems to control applications, due to two main
      factors: signal processing with classification, and users. It is admitted that
      BCI control involves certain characteristics and abilities in its users for
      optimal results. In this study, spatial abilities are evaluated in relation to MI
      BCI control regarding flexion and extension mental tasks. Results show
      considerable correlation (r=0.49) between block design test (visual motor
      execution and spatial visualization) and extension-rest tasks. Additionally,
      rotation test (mental rotation task) presents significant correlation (r=0.56) to
      flexion-rest tasks.

PMID- 29060047
TI  - Facial expression classification using EEG and gyroscope signals.
AB  - In this paper muscle and gyroscope signals provided by a low cost EEG headset
      were used to classify six different facial expressions. Muscle activities
      generated by facial expressions are seen in EEG data recorded from scalp. Using
      the already present EEG device to classify facial expressions allows for a new
      hybrid brain-computer interface (BCI) system without introducing new hardware
      such as separate electromyography (EMG) electrodes. To classify facial
      expressions, time domain and frequency domain EEG data with different sampling
      rates were used as inputs of the classifiers. The experimental results showed
      that with sampling rates and classification methods optimized for each
      participant and feature set, high accuracy classification of facial expressions
      was achieved. Moreover, adding information extracted from a gyroscope embedded
      into the used EEG headset increased the performance by an average of 9 to 16%.

PMID- 29060048
TI  - EEG-based classification of bilingual unspoken speech using ANN.
AB  - The ability to interpret unspoken or imagined speech through
      electroencephalography (EEG) is of therapeutic interest for people suffering from
      speech disorders and 'lockedin' syndrome. It is also useful for brain-computer
      interface (BCI) techniques not involving articulatory actions. Previous work has
      involved using particular words in one chosen language and training classifiers
      to distinguish between them. Such studies have reported accuracies of 40-60% and
      are not ideal for practical implementation. Furthermore, in today's multilingual
      society, classifiers trained in one language alone might not always have the
      desired effect. To address this, we present a novel approach to improve accuracy
      of the current model by combining bilingual interpretation and decision making.
      We collect data from 5 subjects with Hindi and English as primary and secondary
      languages respectively and ask them 20 'Yes'/'No' questions ('Haan'/'Na' in
      Hindi) in each language. We choose sensors present in regions important to both
      language processing and decision making. Data is preprocessed, and Principal
      Component Analysis (PCA) is carried out to reduce dimensionality. This is input
      to Support Vector Machine (SVM), Random Forest (RF), AdaBoost (AB), and
      Artificial Neural Networks (ANN) classifiers for prediction. Experimental results
      reveal best accuracy of 85.20% and 92.18% for decision and language
      classification respectively using ANN. Overall accuracy of bilingual speech
      classification is 75.38%.

PMID- 29060049
TI  - A pilot study on the evaluation of normal phonating function based on high
      density sEMG topographic maps.
AB  - Phonation is controlled by complex synergism of muscles over the front neck
      region. Proper evaluation of the muscular activities in this region would not
      only help to estimate phonation function, but may also provide characteristics to
      diagnose dysphonia. While surface electromyography (sEMG) technique has been used
      to study the physiological aspects of phonation in previous studies, it remains
      unclear if the phonating function could be dynamically characterized by the sEMG
      signals of the neck muscles associated with phonation. In this study, almost 80
      channels of high-density (HD) sEMG signals were acquired from four healthy
      subjects when the vowel /a/ was phonated across different pitches by them. The
      root mean square (RMS) of the HD sEMG signals was computed within a series of
      segmented analysis windows and used to construct dynamic sEMG topographic maps.
      And the RMS maps represented the energy distribution of the front neck muscles,
      which would provide both the temporal and spatial information in accordance with
      the physiological and biomechanical principles of phonation. Our pilot results
      from the sEMG topographic maps across different pitch levels showed that the
      muscular activities consistently increased with the enhancement of the pitch
      levels. This pilot study suggests that HD sEMG might be a potential tool to
      visualize the distribution of the muscular activities and observe the
      coordination of muscular contractions during phonation. Also, it might pave way
      for proper screening and diagnosis of dysphonia as well as its associated
      pathologies.

PMID- 29060050
TI  - Classification of multi-class motor imagery EEG using four band common spatial
      pattern.
AB  - Brain Computer Interfaces (BCIs) serve as an integration tool between acquired
      brain signals and external devices. Precise classification of the acquired brain
      signals with the least misclassification error is an arduous task. Existing
      techniques for classification of multi-class motor imagery electroencephalogram
      (EEG) have low accuracy and are computationally inefficient. This paper
      introduces a classification algorithm, which uses two frequency ranges, mu and
      beta rythms, for feature extraction using common spatial pattern (CSP) along with
      support vector machine (SVM) for classification. The technique uses only four
      frequency bands with no feature reduction and consequently less computational
      cost. The implementation of this algorithm on BCI competition III dataset IIIa,
      resulted in the highest classification accuracy in comparison to existing
      algorithms. A mean accuracy of 85.5 for offline classification has been achieved
      using this technique.

PMID- 29060051
TI  - Information processing of passive joint motion to spinal nervous system.
AB  - The purpose of this work was to investigate the information processing of passive
      joint motion of the rat hindlimb in the spinal nervous system in vivo. Action
      potentials using intracellular recordings and joint kinematics using video
      analysis were measured. The results show that the action potentials of the spinal
      nervous system-evoked passive joint motion were significantly changed. Therefore,
      physical therapy is one of the useful methods for the treatment of joint position
      and angular position sensitivity and spinal nervous system disorders.

PMID- 29060052
TI  - Comparative evaluation of different wavelet thresholding methods for neural
      signal processing.
AB  - Neural signal decoding is the basis for the development of neuroprosthetic
      devices and systems. Depending on the part of the nervous system these signals
      are picked up from, different signal-to-noise ratios (SNR) can be experienced.
      Wavelet denoising is often adopted due to its capability of reducing, to some
      extent, the noise falling within the signal spectrum. Several variables influence
      the denoising quality, but usually the focus in on the selection of the best
      performing mother wavelet. However, the threshold definition and the way it is
      applied to the signal have a significant impact on the denoising quality,
      determining the amount of noise removed and the distortion introduced on the
      signal. This work presents a comparative analysis of different threshold
      definition and thresholding mechanisms on neural signals, either largely adopted
      for neural signal processing or not. In order to evaluate the quality of the
      denoising in terms of the introduced distortion, which is important when decoding
      is implemented through spike-sorting algorithms, a synthetic dataset built on
      real action potentials was used, creating signals with different SNR and
      characterized by an additive white Gaussian noise (AWGN). The obtained results
      reveal the superiority of an approach, originally conceived for noisy non-linear
      time series, over the more typical ones. When compared to the original signal, a
      correlation above 0.9 was obtained, while in terms of root mean square error
      (RMSE) an improvement of 13% and 33% was reported with respect to the Minimax and
      Universal thresholds respectively.

PMID- 29060053
TI  - Multi-resolution multi-trial sparse classification model for decoding visual
      memories from hippocampal spikes in human.
AB  - To understand how memories are encoded in the hippocampus, we build memory
      decoding models to classify visual memories based on hippocampal activities in
      human. Model inputs are spatio-temporal patterns of spikes recorded in the
      hippocampal CA3 and CA1 regions of epilepsy patients performing a delayed match
      to-sample (DMS) task. Model outputs are binary labels indicating categories and
      features of sample images. To solve the super high-dimensional estimation problem
      with short data length, we develop a multi-trial, sparse model estimation method
      utilizing B-spline basis functions with a large range of temporal resolutions and
      a regularized logistic classifier. Results show that this model can effectively
      avoid overfitting and provide significant amount of prediction to memory
      categories and features using very limited number of data points. Stable
      estimation of sparse classification function matrices for each label can be
      obtained with this multi-resolution, multi-trial procedure. These classification
      models can be used not only to predict memory contents, but also to design
      optimal spatio-temporal patterns for eliciting specific memories in the
      hippocampus, and thus have important implications to the development of
      hippocampal memory prostheses.

PMID- 29060054
TI  - Performance analysis of risk-aware control in upper limb of patients with post
      stroke hemiparesis.
AB  - Evidence suggests that humans tune their motor behavior in response to
      environmental uncertainty. Such risk-aware sensorimotor performance is
      hypothetically affected in stroke due to impaired sensorimotor control, but its
      existence and the detailed pattern of impairment remain unclear - particularly
      due to lack of approaches for measurement of dynamic performance in stroke. Here
      we present the design and implementation of a platform for testing the upper-limb
      control in presence of motor uncertainty. The platform monitors how a patient
      with stroke, exclusively with the affected arm, navigates a virtual car by
      adjusting the hand position. We focus on how the control behavior changes when
      the car is perturbed with progressively larger Gaussian noise. Using this
      platform, we successfully collected data from 4 healthy subjects and 4 patients
      with post-stroke hemiparesis. Initial evidence suggests that patients with stroke
      failed to tune their performance with increasing level of Gaussian perturbation.
      The results imply that the risk-aware behavior potentially provides a new
      modality of biofeedback useful in therapeutic interventions.

PMID- 29060055
TI  - A novel HFO-based method for unsupervised localization of the seizure onset zone
      in drug-resistant epilepsy.
AB  - High frequency oscillations (HFOs) are potential biomarkers of epileptic areas.
      In patients with drug-resistant epilepsy, HFO rates tend to be higher in the
      seizure onset zone (SOZ) than in other brain regions and the resection of HFO
      generating areas positively correlates with seizure-free surgery outcome.
      Nonetheless, the development of robust unsupervised HFO-based tools for SOZ
      localization remains challenging. Current approaches predict the SOZ by
      processing small samples of intracranial EEG (iEEG) data and applying patient
      specific thresholds on the HFO rate. The HFO rate, though, varies largely over
      time with the patient's conditions (e.g., sleep versus wakefulness) and across
      patients. We propose a novel localization method for SOZ that uses a time
      varying, HFO-based index to estimate the epileptic susceptibility of the iEEG
      channels. The method is insensitive to the average HFO rate across channels
      (which is both patient- and condition-specific), tracks the channel
      susceptibility over time, and predicts the SOZ based on the temporal evolution of
      the HFO rate. Tested on a preliminary dataset of continuous multi-day
      multichannel interictal iEEG recordings from two epileptic patients (117+/-97.6
      h/per patient, mean +/- S.D.), the reported SOZ prediction had an average 0.70+/
      0.18 accuracy and 0.67+/-0.07 area under the ROC curve (mean +/- S.D.) across
      patients.

PMID- 29060056
TI  - Nanostructured platinum as an electrochemically and mechanically stable electrode
      coating.
AB  - Nanostructured materials exhibit large electrochemical surface areas and are thus
      of high interest for neural interfaces where low impedance and high charge
      transfer characteristics are desired. While progress in nanotechnology
      successively enabled smaller feature sizes and thus improved electrochemical
      properties, concerns were raised with respect to the mechanical stability of such
      nano structures for use in neural applications. In our study we address these
      concerns by investigating the mechanical and electrochemical stability of
      nanostructured platinum. Neural probes with nano-Pt were exposed to exaggerated
      stress tests resembling insertion into neural tissue over 60 mm distance or long
      term stimulation over 240 M biphasic current pulses. Thereby only insignificant
      changes in electrochemical properties and morphological appearance could be
      observed in response to the test, proving that nanostructured platinum exhibits
      outstanding stability. With this finding, a major concern in using nanostructured
      materials for interfacing neural tissue could be eliminated, demonstrating the
      high potential of nanostructured platinum for neuroprosthetic devices.

PMID- 29060057
TI  - Signal correlation between wet and original dry electrodes in
      electroencephalogram according to the contact impedance of dry electrodes.
AB  - The development of dry electroencephalogram (EEG) electrodes is a topic of
      interest. A benefit of using dry EEG electrodes is that they do not require any
      skin preparation. As a result, the condition of the skin with which the dry
      electrodes come in contact is always different among experiments. Thus, in order
      to quantify the performance of EEG recordings using dry electrodes, we need an
      indicator of signal quality for these electrodes. In this study, we showed that
      signal quality changed according to the contact impedance between the skin and
      our dry electrodes. The results indicate that our dry electrodes could record EEG
      signals with high quality when the contact impedance was less than 350 kMU.
      However, contact between the skin and an electrode often changes even during
      experiments, and therefore, we contend that the contact impedance should be
      reduced to less than 300 kMU for safety reasons.

PMID- 29060058
TI  - Design of experiment evaluation of sputtered thin film platinum surface
      metallization on alumina substrate for implantable conductive structures.
AB  - Reliability and reproducibility of implants and their fabrication are highly
      depending on the assembly and packaging procedures. Individual fabrication skills
      like soldering introduce inaccuracies and should be avoided as much as possible.
      Screen printing is often utilized for the metallization of ceramics. Using
      platinum/gold (Pt/Au) paste liquidus diffusion leads to a low adhesion strength
      of the Pt/Au pads after soldering. As an alternative, sputtering of thin film
      surface metallization was investigated. However, this alternative comes with a
      huge amount of different layer and parameter setups. In order to keep the amount
      of experiments and data acquisition in a reasonable magnitude, the Design of
      Experiment (DoE) evaluation displays a powerful tool. We found an optimal layer
      setup that maximizes the adhesion strength of the layer, while simultaneously
      minimizing the sheet resistance and removing the dependency of soldering time.

PMID- 29060059
TI  - High-performance iridium oxide/platinum nano-leaf composite coatings on
      microelectrodes for neural stimulation/recording.
AB  - A novel platinum (Pt) nano-leaf interfacial layer between the Pt substrate and
      iridium oxide (IrOx) coating, significantly reduced impedance and increased
      cathodic charge storage capacity (CSCc) for neural microelectrodes. Combining the
      advantages of both materials, herein a lower impedance and higher CSCc of IrOx/Pt
      nano-leaf composite coatings than each simple coating was fabricated with
      nanoscale roughness. Furthermore, it demonstrated excellent mechanical and
      electrochemical stability, which was beneficial for effective neural
      stimulation/recording in various applications.

PMID- 29060060
TI  - Low SNR neural spike detection using scaled energy operators for implantable
      brain circuits.
AB  - Real time on-chip spike detection is the first step in decoding neural spike
      trains in implantable brain machine interface systems. Nonlinear Energy Operator
      (NEO) is a transform widely used to distinguish neural spikes from background
      noise. In this paper we define a general form of energy operators, of which NEO
      is a specific example, which gives better spike-noise separation than NEO and its
      derivatives. This is because of a non-linear scaling applied to the general
      discrete energy operator. Using two well-known publically available datasets, the
      performance of several operators is compared. On data sets that contain multi
      unit spikes with low Signal to Noise ratio, the detection accuracy was improved
      by approximately 15%.

PMID- 29060061
TI  - Building wireless implantable neural interfaces within weeks for neuroscientists.
AB  - The variety of "'ready-to-use'" implantable recording and stimulation systems
      commercially available for neuroscience is very limited and fabrication of custom
      made implants is commonly considered expensive and time consuming. We present a
      circuit design that allows cost efficient and fast translation of available
      components into fully wireless implants. As demonstration fully wireless
      implantable bidirectional neural interfaces are presented which are made of
      commercial off-the-shelf components (COTS) only. It is demonstrated that they are
      competitive to currently available state-of-the-art systems regarding size and
      performance.

PMID- 29060062
TI  - Safe Direct Current Stimulator design for reduced power consumption and increased
      reliability.
AB  - Current state of the art neural prosthetics, such as cochlear implants, spinal
      cord stimulators, and deep brain stimulators use implantable pulse generators
      (IPGs) to excite neural activity. Inhibition of neural firing is typically
      indirect and requires excitation of neurons that then have inhibitory projections
      downstream. Safe Direct Current Stimulator (SDCS) technology is designed to
      convert electronic pulses delivered to electrodes embedded within an implantable
      device to ionic direct current (iDC) at the output of the device. iDC from the
      device can then control neural extracellular potential with the intent of being
      able to not only excite, but also inhibit and sensitize neurons, thereby greatly
      expanding the possible applications of neuromodulation therapies and neural
      interface mechanisms. While the potential applications and proof of concept of
      this device have been the focus of previous work, the published descriptions of
      this technology leave significant room for power and reliability optimization. We
      describe and model a novel device construction designed to reduce power
      consumption by a factor of 12 and to improve its reliability by a factor of 8.

PMID- 29060064
TI  - 3D printed wire electrode carrier for a pilot study of the functional brain
      mapping.
AB  - In this paper, brain-machine interface (BMI) was adopted to investigate the motor
      area in the animal brain. Stainless steel wire electrodes were implanted to
      search the brain area for rotation, forward movement, and flapping. In
      continuation of our search for optimized coordinates for stimulation, we designed
      electrode case for safer transport and for a more accurate fabrication of the
      electrode array. The cases are customized for each set of coordinates, and
      quickly built using a 3D printer. The case reduced the surgery time and increased
      accuracy in electrode placement. Stimulation of various sites in the brain
      derived the pigeon to move as we have anticipated.

PMID- 29060063
TI  - A miniaturized UWB antenna for implantable data telemetry.
AB  - This paper presents a miniaturized impulse radio ultra-wideband (IR-UWB) antenna
      which is designed for transcutaneous, short-distance data communication used in
      multichannel neural recording. In these systems, with the increasing number of
      recording channels, data rates of 10-100 Mbit/s must be transmitted with very
      limited power and area. Therefore, the antennas are designed as planar,
      ellipsoidal dipoles on a high permittivity substrate with epsilonr = 10.2 to
      achieve high radiation efficiency with small physical size. In order to increase
      the robustness against misalignment, a circularly polarized antenna is used at
      the external receiver unit, reducing the signal power variation under angular
      misalignment. For the transmitting antenna a miniaturized prototype with an
      integrated pulse generator was designed on a round shaped PCB with a diameter of
      only 14mm. Measurements through porcine skin in the frequency domain show an
      attenuation of less than 30dB in the intended frequency band between 6 and
      8.5GHz. Additional evaluations in the time domain prove possible pulse repetition
      rates of up to 100MHz at a transmission distance of 1.5cm.

PMID- 29060065
TI  - A convex-shaped, PDMS-parylene hybrid multichannel ECoG-electrode array.
AB  - Long-term electrode implant is a challenge for successful brain-computer
      interfaces (BCIs). It is well known that electrocorticography (ECoG) using
      flexible planar electrodes is more suitable for long-term implants than
      intracortical neural recordings using penetrative electrodes. In this study, we
      propose a convex-shaped, PDMS-parylene hybrid multi-electrode array for long-term
      stable ECoG recording on the brain or the spinal cord. The electrode array
      consists of 10 gold recording sites which show impedance values between 50 and 70
      kOhm at 1 kHz with a diameter of 100 MUm. It is designed like octopus's leg to
      tightly adhere to the ellipsoidal brain. To assess its performance, epidural ECoG
      recordings were performed from the main olfactory bulb (MOB) of an anesthetized
      rat during odor stimulation. The odor-evoked response was shown with an increase
      of the power in the beta band.

PMID- 29060066
TI  - Flexible microelectrode array for retinal prosthesis.
AB  - fMEA (flexible microelectrode array) is one of the key implantable components for
      neural stimulating and recording. For its specific implanted environment, it
      should be designed and fabricated to meet following requirements such as
      biocompatibility, high-resolution, flexible and low impedance to ensure safety
      and long-term effective stimulation. Here we proposed a high resolution (1025
      channel) fMEA for artificial retina. The adhesion between its substrate polyimide
      (PI) and metal was enhanced by using plasma treatment. The stimulation spots were
      electroplated with Pt-gray, which significantly reduced the electrochemical
      impedance from 110 kMU to 16 kMU at 1 kHz, and also provided larger charge
      storage capacity up to 83.2 mC/cm2. It shows a promising application for neural
      stimulation and recording.

PMID- 29060067
TI  - A comparative study of light and electrically evoked response of retinal ganglion
      cells.
AB  - Understanding of the evoked neural discharges from retinal tissues is vital for
      designing of any retinal prosthesis. In this study, retinal ganglion cell
      activity to light and electrical stimulus is recorded using multielectrode
      arrays. For an effective epiretinal prosthetic device, the electrical stimulus
      through the prosthesis should be able to evoke responses similar to those of
      light response in normal condition. This pilot study was intended to design the
      experimental protocol for in-vitro retinal stimulation. Light and electrical
      stimulus of same duration to normal goat retina evoked different responses.
      Electrical stimulus produces greater number of spikes as compared with light
      response of same duration. With the experimental set up and the analysis
      technique presented here, stimulation parameters such as frequency of input
      pulse, amplitude, type of pulse required to generate responses close to that of
      light response can be optimized.

PMID- 29060068
TI  - Imaging of population spikes induced by repetitive stimulus pulses in mouse
      cerebral slices in vitro.
AB  - Effects of the repetitive current pulses of microstimulation on spatio-temporal
      neuronal excitations in the primary visual cortex in mouse cerebral slices in
      vitro were examined by utilizing the voltage-sensitive dye imaging technique. The
      amplitude and spatial extent of the population spike directly induced by the
      stimulus pulse was significantly reduced in response to successive stimulus
      pulses at 200 Hz. This suggested that the high-frequency microstimulation may not
      be efficient for inducing the neuronal spiking, at least, in vitro.

PMID- 29060069
TI  - Subdural recordings from an awake human brain for measuring current intensity
      during transcranial direct current stimulation.
AB  - Transcranial direct current stimulation (tDCS) is an emerging method, used for
      non-invasively stimulating the brain in normal healthy subjects and in patients
      with neurological disorders. However, the pattern of the spatial distribution of
      the current intensity induced by tDCS is poorly understood. In this study, we
      directly measured the spatial characteristics of the current intensity induced by
      tDCS using an intracranial strip electrode array implanted over the motor cortex
      in patients with Parkinson's disease undergoing deep brain stimulation lead
      placement surgery. We used a bilateral stimulation configuration for the tDCS
      electrode placement and measured the amount of electric current passing through
      the contacts along the implanted strip electrode contacts. Our results showed
      significant changes of the current flow induced by the tDCS in some of the
      contacts during stimulation with respect to baseline activities. These results
      may provide vital information regarding the biophysical effects of tDCS
      stimulation and might be potentially useful for developing more effective
      stimulation strategies.

PMID- 29060070
TI  - Effects of anode position on the responses elicited by transcutaneous spinal cord
      stimulation.
AB  - The purpose of this study was to investigate the effect of anode position on the
      spinal reflex responses evoked by transcutaneous spinal cord stimulation. Healthy
      males participated in two experiments. In Experiment 1 (Exp. 1, n = 3), we
      investigated the effect of anode position on the spinal reflex responses in
      multiple lower-limb muscles. Experiment 2 (Exp. 2, n = 8) focused on the effect
      of anode position on the spinal reflex response in the vastus medialis (VM)
      muscle. In each experiment, electromyographic signals were recorded in the right
      leg muscle(s). The cathode was placed over the area between the spinous processes
      of the L1 and L2 vertebrae. The anode was placed over (1) the abdomen (ABD), (2)
      the ipsilateral (right) anterior superior iliac spine (iASIS), or (3) the
      contralateral (left) anterior superior iliac spine (cASIS). A double pulse
      stimulation test was conducted to confirm that the response was due to activation
      of sensory fibers (i.e. spinal reflex). The results showed that the anode
      position was critical for inducing the spinal reflex in the VM (Exp. 1). The
      ratio of second to first responses was smaller when the anode was placed over the
      ABD or cASIS than when the anode was placed over the iASIS (Exp. 2). In addition,
      the onset latency of the first response was longer when the anode was placed over
      the ABD or cASIS than when the anode was placed over the iASIS (Exp. 2). These
      results showed that the anode should be placed over the ABD or cASIS to
      effectively elicit spinal reflexes in lower-limb muscles.

PMID- 29060071
TI  - A pilot study of planar coil based magnetic stimulation using acute hippocampal
      slice in mice.
AB  - Micromagnetic stimulation using small-sized implantable coils has recently been
      studied. The main advantage of this method is that it can provide sustainable
      stimulation performance even if a fibrotic encapsulation layer is formed around
      the implanted coil by inflammation response, because indirectly induced currents
      are used to induce neural responses. In previous research, we optimized the
      geometrical and control parameters used in implantable magnetic stimulation.
      Based on those results, we fabricated the planar coil and studied the LTP effect
      in the hippocampal slice by two different magnetic stimulation protocols using
      the quadripulse stimulation (QPS) pattern. We found that direct magnetic
      stimulation (DMS) induced insignificant LTP effect and priming magnetic
      stimulation (PMS) occluded LTP effect after tetanic stimulation, when QPS
      patterned magnetic stimulation with 1 A current pulse was applied to the planar
      coil.

PMID- 29060072
TI  - Localization of ultrasound waveform for low intensity ultrasound-induced
      neuromodulation in a mouse model.
AB  - A collimator design was investigated to localize ultrasound stimulation using a
      flat ultrasound transducer for ultrasound-induced neuromodulation in a mouse
      model. In brain stimulation, the specific location of stimulation must be
      specified, as the region responsible for motor or sensory function is clustered
      in a narrow brain area. To localize ultrasound stimulation, three types of
      collimator design were simulated to determine the optimal collimator design. The
      performance of the simulated optimal collimator was compared to that of an
      unmounted collimator in a transducer in both in vivo and in vitro experiments.
      Throughout the experiments, the localized ultrasound waveform was shaped using
      the optimized collimator, which elicited neural spike activity in the targeted
      motor cortex. The optimized collimator shows potential for controlling a
      localized ultrasound waveform for ultrasound-induced neuromodulation in a small
      animal model.

PMID- 29060073
TI  - Research on the synchronous detection of neuronal signals under a nerve
      stimulation system control.
AB  - Deep brain stimulation (DBS) provides a recognized research intervention for
      neurological disease currently. However, there is a lack of traditional
      electrical stimulator to observe neuronal firing activity synchronously. The aim
      of the present study was to realize concurrent detection of neuronal signals
      better under a nerve stimulation system control. Herein, we designed an
      integrated software, which could control not only neuro-stimulator but also
      detection instrument at the same time. Moreover, the actual stimulation signals
      applied to the experiment object could be collected back to data acquisition card
      and in consistent with the electrophysiological signals. As to basic performance
      of self-building stimulator, the accuracy of output square signal was verified to
      be greater than 99.05 % with the change of voltage amplitude. Practicably,
      combined with homemade microelectrode array (MEA) detecting device, medial
      forebrain bundle (MFB) DBS effects were observed significantly through the
      changes of electrophysiological signals in caudate putamen (CPu) of Sprague
      Dawley (SD) rat, and the signal-to-noise ratio (SNR) was 5:1 after stimulation.
      Therefore, the comprehensive nerve stimulation system, which consists of neuro
      stimulator and integrated software, could be widely used in the field of
      neuroscience research with high precision and synchronization.

PMID- 29060074
TI  - In-vitro validation of a closed-loop optogenetic stimulation device.
AB  - Closed-loop optogenetic stimulation (CLOS) involves real-time neural data
      collection and analysis, feedback control, and optical neuromodulation. Despite
      emergence of the CLOS devices, methods for validating such devices in-vitro are
      limited. This paper presents a CLOS device and introduces an in-vitro setup for
      validating CLOS devices. The CLOS device consists of an electrode, a neural
      detector, a control algorithm, and an optogenetic stimulator. The in-vitro setup
      consists of saline solution, a neural signal emitter, a photodiode and its
      amplifier, and a closed-loop simulation program. Synthetic neural signals are
      delivered to the CLOS device, and based on the sensed optical stimulations from
      the light source, the properties of the delivered neural signals are changed.
      Experiments are conducted to evaluate the closed-loop operation of the CLOS
      device, and verify the capability of the in-vitro setup to for validating the
      CLOS devices. The in-vitro setup enables refinement of CLOS devices before
      arduous in-vivo trials.

PMID- 29060075
TI  - Optimal inter-stimulus interval for paired associative stimulation with
      mechanical stimulation.
AB  - In this paper, inter-stimulus interval (ISI) of paired associative stimulation
      (PAS) with mechanical stimulation was analyzed. PAS is a prominent therapeutic
      intervention for individuals after stroke and helps to improve limb function by
      strengthening excitatory synapses and inducing neural plasticity. This
      intervention involves repeated application of transcranial magnetic stimulation
      (TMS) followed by peripheral stimulation. When responses to both stimulations are
      overlapped in the brain at the same time, this successful PAS is expected to
      induce long term potentiation (LTP) which leads to a neural plasticity
      phenomenon. Therefore ISI between these two stimulations is very crucial in this
      treatment. Instead of electrical stimulation in general PAS, mechanical
      stimulation was used in this study due to some promising aspects of mechanical
      stimulation. Long latency stretch response (LLSR) was observed in
      electromyography (EMG) during the PAS with mechanical stimulation, since LLSR
      reflects successful overlapping of two stimulations. Each subject had specific
      range of ISIs, or a time window, that leads to successful overlapping of paired
      stimulations. These time window lengths varied between 5ms and 105 ms, and within
      this range it can be guaranteed to obtain LLSR in EMG at least 40% among the all
      PAS trials. In addition, normally distributed responses within time window
      suggests that the optimal ISI which results in the highest number of LLSRs is the
      average of the time window. This result suggests that PAS with mechanical
      stimulation could lead to a rehabilitation effect by regaining motor
      functionality when the two stimulations are paired with the optimal ISI and it
      could provide a significant advancement in neuromodulation.

PMID- 29060076
TI  - Restoring proper task mechanics of the hand post-stroke by targeted assistance of
      hand muscles.
AB  - Significant impairment in hand function is found prevalent among stroke
      survivors, but its effective restoration is challenging due to the complexity of
      the functional tasks of the hand. In this study, we proposed a novel approach to
      improve functionality of the hand post-stroke by providing 'subject-specific'
      patterns of targeted assistance to impaired musculotendon of the hand during
      functional task performance. Eleven chronic stroke survivors participated in the
      experiment in which a biomimetic device provided targeted assistance to the
      impaired hand musculotendons. The proposed subject-specific approach was found to
      restore proper mechanics of two functional tasks, hand open and palmar pinch, as
      quantified by the joint kinematics and fingertip force direction. The range of
      motion and joint coordination was improved for the hand open task, and the
      fingertip force was directed towards normal direction by the targeted assistance
      of impaired muscles. The assistance pattern was significantly different across
      subjects, indicating significant between-subject variability in the impairment
      characteristics that affect task performance. The proposed method could enable an
      effective 'subject-specific' training method that restores proper mechanics of
      functional hand tasks for stroke survivors.

PMID- 29060077
TI  - Weight drop impact system and its output signal analysis for inducing large
      animal spinal cord injury model.
AB  - Weight drop style impact systems can be used as a tool to induce the acute spinal
      cord injury (SCI) in large animals. We introduce our cost-effective impact system
      for the SCI modeling without using an expensive high speed camera and a vision
      system. And the practical output signals obtained in porcine in-vivo experiments
      using our system have been analyzed to check the effects of surrounding bones,
      tissues, and bleedings over the impacting target position in the spinal cord. By
      analyzing the output signals, the abnormal impact results hindered by the
      surrounding structures could have been separated from the normally impacted ones.

PMID- 29060078
TI  - Motor imagery enhancement paradigm using moving rubber hand illusion system.
AB  - Motor imagery (MI) has been widely used in neurorehabilitation and brain computer
      interface. The size of event-related desynchronization (ERD) is a key parameter
      for successful motor imaginary rehabilitation and BCI adaptation. Many studies
      have used visual guidance for enhancement/ amplification of motor imagery ERD
      amplitude, but their enhancements were not significant. We propose a novel ERD
      enhancing paradigm using body-ownership illusion, or also known as rubber hand
      illusion (RHI). The system was made by motorized, moving rubber hand which can
      simulate wrist extension. The amplifying effects of the proposed RHI paradigm
      were evaluated by comparing ERD sizes of the proposed paradigm with motor imagery
      and actual motor execution paradigms. The comparison result shows that the
      improvement of ERD size due to the proposed paradigm was statistically
      significant (p<;0.05) compared with the other paradigms.

PMID- 29060079
TI  - The impact of an anti-gravity treadmill (AlterG) training on walking capacity and
      corticospinal tract structure in children with cerebral palsy.
AB  - We studied the effects of an anti-gravity treadmill (AlterG) training on walking
      capacity and corticospinal tract structure in children with Cerebral Palsy (CP).
      AlterG can help CP children walk on the treadmill by reducing their weights up to
      80% and maintain their balance during locomotion. AlterG training thus has the
      potential to improve walking capacity permanently as it can provide systematic
      and intense locomotor training for sufficiently long period of time and produce
      brain neuroplasticity. AlterG training was given for 45 minutes, three times a
      week for two months. The neuroplasticity of corticospinal tract was evaluated
      using Diffusion Tensor Imaging (DTI). The fractional Anisotropy (FA) feature was
      extracted to quantify structural changes of the corticospinal tract. Walking
      capacity was evaluated using popular clinical measurements of gait; i.e., walking
      speed, mobility and balance. The evaluations were done before and after training.
      Our results revealed that AlterG training resulted in an increase in average FA
      value of the corticospinal tract following the training. The outcome measures of
      clinical assessments of gait presented enhanced walking capacity of the CP
      subjects. Our findings indicated that the improved walking capacity was
      concurrent with the enhancement of the corticospinal tract structure. The
      clinical implication is that AlterG training may be considered as a therapeutic
      tool for permanent gait improvement in CP children.

PMID- 29060080
TI  - Quantitative assessment test for upper-limb motor function by using EMG and
      kinematic analysis in the practice of occupational therapy.
AB  - This paper proposes a quantitative assessment test of stroke patients' upper limb
      motor functions during occupational therapy. Conventional assessments are
      performed based on therapists' observations and subjective judgments which make
      it hard to recognize the qualitative functional changes. To suggest quantitative
      function indices, we measured electromyogram and kinematic parameters from 6
      stroke patients during the 'stacking cones' task and the 'ROM arc' task using
      motion sensors and EMG sensor attached on the brachial, and analyzed motor
      functions. The selected indices that represent the motor function were the mean
      of angular velocity, the number of extrema, and the difference between tension of
      flexor (FCU, FCR and Brachioradialis m.) and extensor ECU, ECR and EDM). We
      compared the indices of affected and less affected upper limbs of each subject
      and it showed statistical significance during the given tasks (p<;0.05).
      Therefore, the quantitative assessment is expected to integrate the process of
      treatment and evaluation.

PMID- 29060081
TI  - A preliminary study to identify a neurophysiological correlate of electroacoustic
      pitch matching in cochlear implant users.
AB  - One challenge facing postlingually-deafened cochlear implant (CI) users is the
      frequency mismatch between the incoming acoustic signal and the characteristic
      frequency of the electrically stimulated neurons. Current CI is an open-loop
      system and it requires extensive fine-tuning to help users to adapt to this
      mismatch over time. Electric-acoustic pitch matching in unilateral cochlear
      implant (CI) participants who has residual hearing in the non-implanted ear had
      been shown to serve as a useful metric to monitor adaptation process. The goal of
      this study was to identify a potential neurophysiological correlate to this
      electroacoustic pitch matching for a possible metric to track the adaptation
      process of CI users over time and a possible feedback for a closed-loop CI system
      design. This study utilized a method of presenting electrical and acoustic
      stimuli that were continuously alternating across ears. The stimuli were either
      matched or mismatched in pitch. Auditory Evoked Potentials (AEP) were recorded
      from 10 CI users and 10 normal hearing (NH) participants. For NH participants, an
      acoustic tone at a fixed frequency was presented in place of electrical
      stimulation. Results with CI participants indicated that N1 latency decreases
      when the acoustic frequency of the tone presented in the non-implanted ear
      increases. More importantly, there was an additional shortening of N1 latency in
      the pitch matched condition. These two patterns were repeated with NH
      participants. These results indicate the potential utility of N1 latency as an
      index of pitch matching in both normal hearing listeners and cochlear implant
      user.

PMID- 29060082
TI  - Retinal electrostimulation in rats: Activation thresholds from superior
      colliculus and visual cortex recordings.
AB  - Retinal neuromodulation is an emerging therapeutic approach to restore functional
      vision to those suffering retinal photoreceptor degeneration. The retina encodes
      visual information and transmits it to the brain. Replicating this retinal code
      through electrical stimulation is essential to improving the performance of
      visual prostheses. In doing so, the first step relies on precise neural
      recordings from visual centers that allow studying the response of these neurons
      to electrical stimulation of the retina. This paper demonstrates the feasibility
      of a rat model to conduct highly reliable electrophysiological studies in the
      field of retinal neuromodulation. A disc electrode, implanted in the retrobulbar
      space was used to stimulate the retina of Long-Evans rats. Buzsaki multi-electro
      arrays were inserted in the superior colliculus (SC) to record electrical
      activity propagated from the retinal ganglion cells (RGCs). Activation thresholds
      calculated from local field potentials (visual cortex) and from neural spikes
      (SC) were contrasted. Both values were comparable to those in humans and in other
      animal models, and were slightly higher when estimated from SC recordings.
      However, differences were not statistically significant.

PMID- 29060083
TI  - Testing stimulus protocols in retinal-prosthesis patients.
AB  - Retinal prostheses have demonstrated the capability to give blind patients the
      ability to detect motion and locate large objects. High-resolution retinal
      prostheses require precise activation of retinal cells to elicit a small visual
      phosphine that can serve as a building block to make patterns. Each electrode
      should activate only nearby cells, however patients receiving single electrode
      stimulation often report a streak-shaped phosphene rather than a focal spot. It
      is important to investigate stimulus paradigms that will provide better control
      over the spatial patterns of activation. During this study a 55 year old patient
      implanted with the Argus II system on August 2015 was tested with single
      electrode stimulation and pattern stimulation experiments. Tasks were performed
      using Argus II normal parameters.

PMID- 29060085
TI  - Video analysis of "YouTube funnies" to aid the study of human gait and falls -
      preliminary results and proof of concept.
AB  - Because falls are funny, YouTube and other video sharing sites contain a large
      repository of real-life falls. We propose extracting gait and balance information
      from these videos to help us better understand some of the factors that
      contribute to falls. Proof-of-concept is explored in a single video containing
      multiple (n=14) falls/non-falls in the presence of an unexpected obstacle. The
      analysis explores: computing spatiotemporal parameters of gait in a video
      captured from an arbitrary viewpoint; the relationship between parameters of gait
      from the last few steps before the obstacle and falling vs. not falling; and the
      predictive capacity of a multivariate model in predicting a fall in the presence
      of an unexpected obstacle. Homography transformations correct the perspective
      projection distortion and allow for the consistent tracking of gait parameters as
      an individual walks in an arbitrary direction in the scene. A synthetic top view
      allows for computing the average stride length and a synthetic side view allows
      for measuring up and down motions of the head. In leave-one-out cross-validation,
      we were able to correctly predict whether a person would fall or not in 11 out of
      the 14 cases (78.6%), just by looking at the average stride length and the range
      of vertical head motion during the 1-4 most recent steps prior to reaching the
      obstacle.

PMID- 29060084
TI  - Identifying personal health experience tweets with deep neural networks.
AB  - Twitter, as a social media platform, has become an increasingly useful data
      source for health surveillance studies, and personal health experiences shared on
      Twitter provide valuable information to the surveillance. Twitter data are known
      for their irregular usages of languages and informal short texts due to the 140
      character limit, and for their noisiness such that majority of the posts are
      irrelevant to any particular health surveillance. These factors pose challenges
      in identifying personal health experience tweets from the Twitter data. In this
      study, we designed deep neural networks with 3 different architectural
      configurations, and after training them with a corpus of 8,770 annotated tweets,
      we used them to predict personal experience tweets from a set of 821 annotate
      tweets. Our results demonstrated a significant amount of improvement in
      predicting personal health experience tweets by deep neural networks over that by
      conventional classifiers: 37.5% in accuracy, 31.1% in precision, and 53.6% in
      recall. We believe that our method can be utilized in various health surveillance
      studies using Twitter as a data source.

PMID- 29060086
TI  - 3-year risk prediction of Coronary Heart Disease in hypertension patients: A
      preliminary study.
AB  - Hypertension is associated with increased morbidity and mortality in Coronary
      Heart Disease (CHD). However, the risk factors that cause hypertension patients
      develop into CHD remain unclear. This paper aims to study traditional and
      nontraditional risk factors of CHD in hypertension population. Data were
      extracted from the regional medical big data system of Shenzhen, a big city of
      China. In this study, we included 3395 hypertension patients aged from 30 to 79
      years old. Among them, 1153 CHD events occurred within 3 years after they were
      first followed-up. A logistic regression model was used to evaluate the risk
      factors quantitatively and predict 3-year risk of CHD events. The results showed
      that traditional general-population-based CHD risk factors such as age, body mass
      index, diabetes, hyperlipemia, and chronic kidney disease still remained
      predictive in hypertension patients. In addition, the odds ratio (95% confidence
      interval) of CHD was 1.54 (1.19 to 2.01) for emotional or mental disorders, and
      1.69 (1.21 to 2.34) for sleep disorders. And the model showed a good
      discriminative performance with an AUC of 0.839. It offered a new insight for
      hypertension patients that keeping psychological health and maintaining a good
      sleep quality could be helpful in preventing CHD. Given the high risk for CHD in
      patients with hypertension, control of these risk factors may have a substantial
      preventive effect on CHD.

PMID- 29060087
TI  - Prediction of Influenza A virus infections in humans using an Artificial Neural
      Network learning approach.
AB  - The Influenza type A virus can be considered as one of the most severe viruses
      that can infect multiple species with often fatal consequences to the hosts. The
      Haemagglutinin (HA) gene of the virus has the potential to be a target for
      antiviral drug development realised through accurate identification of its sub
      types and possible the targeted hosts. In this paper, to accurately predict if an
      Influenza type A virus has the capability to infect human hosts, by using only
      the HA gene, is therefore developed and tested. The predictive model follows
      three main steps; (i) decoding the protein sequences into numerical signals using
      EIIP amino acid scale, (ii) analysing these sequences by using Discrete Fourier
      Transform (DFT) and extracting DFT-based features, (iii) using a predictive
      model, based on Artificial Neural Networks and using the features generated by
      DFT. In this analysis, from the Influenza Research Database, 30724, 18236 and
      8157 HA protein sequences were collected for Human, Avian and Swine respectively.
      Given this set of the proteins, the proposed method yielded 97.36% (+/- 0.04%),
      97.26% (+/- 0.26%), 0.978 (+/- 0.004), 0.963 (+/- 0.005) and 0.945 (+/-0.005) for
      the training accuracy validation accuracy, precision, recall and Mathews
      Correlation Coefficient (MCC) respectively, based on a 10-fold cross-validation.
      The classification model generated by using one of the largest dataset, if not
      the largest, yields promising results that could lead to early detection of such
      species and help develop precautionary measurements for possible human
      infections.

PMID- 29060088
TI  - Data quality improvement of a multicenter clinical trial dataset.
AB  - Medical datasets are usually affected by several problems, such as missing
      values, inconsistencies, redundancies, that can influence the data mining process
      and the extraction of useful knowledge. For these reasons, a preprocessing phase
      should be performed for improving the overall quality of data and, consequently,
      of the information that may be discovered from them. In this study we applied
      five steps of data preprocessing to improve the quality of a large dataset
      derived from a multicenter clinical trial. Our dataset included 298 patients
      enrolled in a prospective, multicenter, clinical trial, characterized by 22 input
      variables and one class variable (MIPI value). In particular, data coming from
      different medical centers were firstly integrated to obtain a homogeneous
      dataset. The latter was normalized to scale all variables into smaller and
      similar intervals. Then, all missing values were estimated by means of an
      imputation step. The complete dataset was finally discretized and reduced to
      remove redundant variables and decrease the amount of data to be managed. The
      improvement of data quality after each step was evaluated by means of the
      patients' classification accuracy using the KNN classifier. Our results showed
      that the proposed pipeline produced an increment of more than 20% of the
      classification performances. Moreover, the highest growth of accuracy was
      obtained after missing value imputation, whereas the discretization and feature
      selection steps allowed for a significant reduction of variables to be managed,
      without any deterioration of the information contained in data.

PMID- 29060089
TI  - Discovering explanatory models to identify relevant tweets on Zika.
AB  - Zika virus has caught the worlds attention, and has led people to share their
      opinions and concerns on social media like Twitter. Using text-based features,
      extracted with the help of Parts of Speech (POS) taggers and N-gram, a classifier
      was built to detect Zika related tweets from Twitter. With a simple logistic
      classifier, the system was successful in detecting Zika related tweets from
      Twitter with a 92% accuracy. Moreover, key features were identified that provide
      deeper insights on the content of tweets relevant to Zika. This system can be
      leveraged by domain experts to perform sentiment analysis, and understand the
      temporal and spatial spread of Zika.

PMID- 29060090
TI  - Fast segmentation and modeling of hepatic components for the planning of robot
      assisted liver tumor ablation.
AB  - Segmentation and modeling of hepatic components from pre-operative images is very
      important for treatment planning and guidance in robot-assisted liver tumor
      ablation. An in-house developed system for hepatic component segmentation and
      modeling using CT data is presented in this paper. This system includes gross
      liver segmentation by a 3D mesh deformation model, liver vasculature segmentation
      by a vessel context-based voting and grouping method, liver tumor segmentation by
      a support vector machine framework, and other segmentation/modeling tool. This
      system was tested using 20 data sets from human patients and 5 sets of porcine CT
      scan. It is suggested by experimental results that the developed system is able
      to conduct fast segmentation and modeling of hepatic components for both human
      and large animal, with a satisfying accuracy, to support treatment planning.

PMID- 29060091
TI  - Cloud solution for histopathological image analysis using region of interest
      based compression.
AB  - Recent technological gains have led to the adoption of innovative cloud based
      solutions in medical imaging field. Once the medical image is acquired, it can be
      viewed, modified, annotated and shared on many devices. This advancement is
      mainly due to the introduction of Cloud computing in medical domain. Tissue
      pathology images are complex and are normally collected at different focal
      lengths using a microscope. The single whole slide image contains many multi
      resolution images stored in a pyramidal structure with the highest resolution
      image at the base and the smallest thumbnail image at the top of the pyramid.
      Highest resolution image will be used for tissue pathology diagnosis and
      analysis. Transferring and storing such huge images is a big challenge.
      Compression is a very useful and effective technique to reduce the size of these
      images. As pathology images are used for diagnosis, no information can be lost
      during compression (lossless compression). A novel method of extracting the
      tissue region and applying lossless compression on this region and lossy
      compression on the empty regions has been proposed in this paper. The resulting
      compression ratio along with lossless compression on tissue region is in
      acceptable range allowing efficient storage and transmission to and from the
      Cloud.

PMID- 29060092
TI  - Analysis of computerized optokinetic nystagmus induction and effect of contrast
      on ocular fatigue.
AB  - Optokinetic nystagmus (OKN) is useful in evaluating visual function objectively,
      and the classical black-and-white-striped OKN drum is being replaced by video or
      computer monitor. However, the examinee may feel fatigue during test because of
      high contrast of luminous pattern from monitor. This paper suggests a plan to
      reduce eye fatigue of participant by decreasing contrast of patterns without
      reducing OKN response. Alternating black and white stripes are shown on flat
      panel liquid-crystal display monitor and moved horizontally to evoke OKN of the
      examinee, and the OKN wasW observed through electrooculography (EOG). Eye fatigue
      was estimated from the number of eye blinking, along with dry eye questionnaire
      according to the contrast of the black and white stripes. White stripes are shown
      as 300cd/m2, and gradual decrement in contrast by 75%, 50%, and 25% were given to
      investigate the effect of the contrast on the eye fatigue and the OKN. Blinking
      of the eye was recorded as a video clip and was analyzed by image processing to
      count the number of blinks while measuring OKN. Experimental results show that
      incidence of nystagmus does not substantially change with the change of contrast
      in stimulus pattern but the eye fatigue decreased by the reduction of the
      contrast. In conclusion, the examinee may choose the contrast option for the OKN
      test to reduce the stress onto their eye, without affecting the test result.

PMID- 29060093
TI  - MRI based automated diagnosis of Alzheimer's: Fusing 3D wavelet-features with
      clinical data.
AB  - This paper presents a novel algorithm for classification of patients with
      Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) from the healthy
      controls (HC) using structural MRI. Feature extraction is based on discrete 3D
      wavelet transform followed by PCA for transforming the feature space into
      linearly uncorrelated variables. Linear SVM is used for classification purposes
      with clinical dementia rating used as the target vector. Proposed methodology is
      fully automated and independent of the annotation of region of interest. The
      importance of MRI, demographical data, neuro-psychiatric test scores and
      statistics calculated over the wavelet coefficients for the classification is
      studied. Proposed methodology is applied on 197 subjects from a public database.
      A classification accuracy of 95% was achieved for the case of HC vs AD. For the
      case of HC vs MCI, and MCI vs AD the classification accuracy of 78% and 81% were
      achieved. The results are compared with an existing state of the art technique.

PMID- 29060094
TI  - Semi-automated nasal PAP mask sizing using facial photographs.
AB  - We present a semi-automated system for sizing nasal Positive Airway Pressure
      (PAP) masks based upon a neural network model that was trained with facial
      photographs of both PAP mask users and non-users. It demonstrated an accuracy of
      72% in correctly sizing a mask and 96% accuracy sizing to within 1 mask size
      group. The semi-automated system performed comparably to sizing from manual
      measurements taken from the same images which produced 89% and 100% accuracy
      respectively.

PMID- 29060095
TI  - A hybrid approach for nucleus stain separation in histopathological images.
AB  - Difficulties in automation of histology image analysis are caused due to varying
      stain colors in the histology slides and the interaction of stains. Incorrect
      stain separation results in incorrect nucleus segmentation. A new hybrid
      algorithm has been proposed combining de-staining and wedge separation
      algorithms, which provides better stain separation and maintains color integrity
      of the input image. The proposed algorithm is tested on 36 histopathological
      images covering varying tissues and compared with popular methods in the area
      with excellent results in high nuclei density category.

PMID- 29060096
TI  - Assisting people with Nystagmus through image stabilization: Using an ARX model
      to overcome processing delays.
AB  - Pathological Nystagmus is characterized by an unintended and involuntary eye
      movement, which tends to impact on visual acuity. Today only view therapies (for
      instance medication or surgeries) to treat nystagmus are at hand and the existing
      therapies only show partial improvement. Only general Assistive Technology (AT)
      solutions like glasses, screen magnifiers, speech output, display adaptation and
      concepts holders are at hand to support daily living. More specific ATs to reduce
      the impact of nystagmus are missing. This paper presents conceptual research and
      feasibility studies with the attempt to reduce the impact of nystagmus by
      stabilizing the image on the retina (digital Retinal Image Stabilization) by
      moving the digital image synchronal with the unintended eye movement using gaze
      contingent display technology. Further an identification and validation process
      using recorded eye-movements is presented since the synchronization approach
      relies on predicting eye-movements to reduce the impact of delays due to
      processing time.

PMID- 29060097
TI  - Software implementation and hardware acceleration of retinal vessel segmentation
      for diabetic retinopathy screening tests.
AB  - Screening tests are an effective tool for the diagnosis and prevention of several
      diseases. Unfortunately, in order to produce an early diagnosis, the huge number
      of collected samples has to be processed faster than before. In particular this
      issue concerns image processing procedures, as they require a high computational
      complexity, which is not satisfied by modern software architectures. To this end,
      Field Programmable Gate Arrays (FPGAs) can be used to accelerate partially or
      entirely the computation. In this work, we demonstrate that the use of FPGAs is
      suitable for biomedical application, by proposing a case of study concerning the
      implementation of a vessels segmentation algorithm. The experimental results,
      computed on DRIVE and STARE databases, show remarkable improvements in terms of
      both execution time and power efficiency (6X and 5.7X respectively) compared to
      the software implementation. On the other hand, the proposed hardware approach
      outperforms literature works (3X speedup) without affecting the overall accuracy
      and sensitivity measures.

PMID- 29060098
TI  - Detection and classification of the breast abnormalities in digital mammograms
      via regional Convolutional Neural Network.
AB  - Automatic detection and classification of the masses in mammograms are still a
      big challenge and play a crucial role to assist radiologists for accurate
      diagnosis. In this paper, we propose a novel computer-aided diagnose (CAD) system
      based on one of the regional deep learning techniques: a ROI-based Convolutional
      Neural Network (CNN) which is called You Only Look Once (YOLO). Our proposed YOLO
      based CAD system contains four main stages: mammograms preprocessing, feature
      extraction utilizing multi convolutional deep layers, mass detection with
      confidence model, and finally mass classification using fully connected neural
      network (FC-NN). A set of training mammograms with the information of ROI masses
      and their types are used to train YOLO. The trained YOLO-based CAD system detects
      the masses and classifies their types into benign or malignant. Our results show
      that the proposed YOLO-based CAD system detects the mass location with an overall
      accuracy of 96.33%. The system also distinguishes between benign and malignant
      lesions with an overall accuracy of 85.52%. Our proposed system seems to be
      feasible as a CAD system capable of detection and classification at the same
      time. It also overcomes some challenging breast cancer cases such as the mass
      existing in the pectoral muscles or dense regions.

PMID- 29060099
TI  - Evaluation of NISHIJIN e-textile for 12-lead ECG measurement through automatic
      ECG analyzer.
AB  - The authors are developing e-textile measuring 12-lead ECG signal based using a
      historical brocade developing technique, NISHIJIN-ORI. In this paper, a NISHIJIN
      e-textile sensor belt prototype designed for ambulatory measurement (pre-hospital
      12-lead ECG measurement) was tested on twenty volunteers. The recorded data was
      evaluated through the result of commercial automatic ECG analyzer. The obtained
      results are almost equivalent with the ones obtained through conventional ECG
      electrodes. However, the results suggest slight modification of the prototype.

PMID- 29060100
TI  - Edge caching and Dynamic Vision Sensing for low delay access to visual medical
      information.
AB  - A new system is proposed to reduce the transmission delay of visual and non
      visual medical records by using edge caching and Dynamic Vision Sensing (DVS)
      technologies. The results of simulation show that the proposed scheme can
      decrease the transmission delay by 36.35% to 86.88% compared to a system with
      edge caching only.

PMID- 29060101
TI  - Recognizing cigarette smoke inhalations using hidden Markov models.
AB  - Previous studies with the Personal Automatic Cigarette Tracker (PACT) wearable
      system have found that smoking presents a distinct temporal breathing pattern,
      which might be well-suited for recognition by hidden Markov models (HMMs). In
      this work, we explored the feasibility of using HMMs to characterize the temporal
      information of smoking inhalations contained in the respiratory signals such as
      tidal volume, airflow, and the signal from the hand-to-mouth proximity sensor.
      Left-to-right HMMs were built to classify smoking and non-smoking inhalations
      using either only the respiratory signals, or both respiratory and hand proximity
      signals. Using a data set of 20 subjects, a leave-one-out cross-validation was
      performed on each HMM. In the recognition of smoke inhalations, the highest
      average recall, precision and F-score perceived by the HMMs was 42.39%, 88.19%
      and 56.38%, respectively, providing a 7.3% improvement in recall against a
      previously reported Support Vector Machines.

PMID- 29060102
TI  - Electromyogram-based method to secure wireless body sensor networks for
      rehabilitation systems.
AB  - Wireless body sensor networks (WBSNs) provide a platform to track and monitor
      human health status as well as feedback to the user by capturing and processing
      certain physiological signals. Since WBSNs need to provide efficient health
      information privacy, their security has been identified as one of the major
      challenges, especially for rehabilitation systems. Conventionally, the random
      numbers (RNs) based on the inter-pulse intervals (IPIs) from electrocardiogram
      (ECG) recordings have been widely used to secure the data in WBSNs. However, this
      method is limited in real-time applications such as human posture control. In
      this study, we proposed a novel electromyogram (EMG) based RN generation method
      to secure the data acquired from WBSNs systems for rehabilitation. The newly
      proposed security scheme was tested on EMG signals acquired from 15 healthy
      subjects by using EMG features. These features were coded into 128-bit RNs with
      entropy values ranging from 0.96 to 1.00, and hamming distances (HDs) that ranged
      from 41 to 83. These preliminary results showed that randomness and
      distinctiveness of those RNs are good enough for authentication and encryption.
      Findings from the current study suggest that the EMG-based RN generation method
      would be potential in securing the health information in WBSNs.

PMID- 29060103
TI  - A tapping device for recording and quantitative characterization of
      rhythmic/auditory sequences.
AB  - The processing of auditory stimuli is essential for the correct perception of
      language and deficits in this ability are often related to the presence or
      development of language disorders. The motor imitation (e.g. tapping or beating)
      of rhythmic sequences can be a very sensitive correlate of deficits in auditory
      processing. Thus, the study of the tapping performance, with the investigation of
      both temporal and intensity information, might be very useful. The present work
      is aimed at the development and preliminary testing of a tapping device to be
      used for the imitation and/or the production of rhythmic sequences, allowing the
      recording of both tapping duration and intensity. The device is essentially made
      up of a Force Sensing Resistor and an Arduino UNO board. It was validated using
      different sampling frequencies (fs) in a group of 10 young healthy adults
      investigating its efficacy in terms of touch and intensity detection by means of
      two testing procedures. Results demonstrated a good performance of the device
      when programmed with fs equal to 50 and 100Hz. Moreover, both temporal and
      intensity parameters were extracted, thus supporting the potential use of the
      device for the analysis of the imitation or production of rhythmic sequences.
      This work represents a first step for the development of a useful, low cost tool
      to support the diagnosis, training and rehabilitation of language disorders.

PMID- 29060104
TI  - Development of the viewing distance measuring device in smartphone use.
AB  - In this paper, a low-cost lens fabrication method using a micro chamber produced
      by a three-dimensional (3-D) printer is presented. The shape of
      polydimethylsiloxane (PDMS) membrane was controlled by adjusting the pressure
      inside the chamber. On top of the shaped membrane, an ultraviolet-curable resin
      was poured. Depending on the pressure inside the chamber and the shape of the
      chamber lid, three types of lenses could be made: a bi-convex lens, a plano
      convex lens, and a concave lens. This method can reduce the cost of making pilot
      or evaluation devices in healthcare service.

PMID- 29060105
TI  - Chewing detection from an in-ear microphone using convolutional neural networks.
AB  - Detecting chewing sounds from a microphone placed inside the outer ear for eating
      behaviour monitoring still remains a challenging task. This is mainly due the
      difficulty in discriminating non-chewing sounds (e.g. speech or sounds caused by
      walking) from chews, as well as due to to the high variability of the chewing
      sounds of different food types. Most approaches rely on detecting distictive
      structures on the sound wave, or on extracting a set of features and using a
      classifier to detect chews. In this work, we propose to use feature-learning in
      the time domain with 1-dimensional convolutional neural networks for for chewing
      detection. We apply a network of convolutional layers followed by fully connected
      layers directly on windows of the audio samples to detect chewing activity, and
      then aggregate individual chews to eating events. Experimental results on a
      large, semi-free living dataset collected in the context of the SPLENDID project
      indicate high effectiveness, with an accuracy of 0.980 and F1 score of 0.883.

PMID- 29060106
TI  - Automated long-term contactless temperature monitoring in animals via a
      thermographic camera.
AB  - The paper deals with a problem of a remote prolonged temperature monitoring of
      biological objects. It presents an algorithm for automatic analysis and
      processing of video recording from a thermographic camera. Special attention is
      paid to the limitation of the method taking into account the possibility of its
      utilizing in laboratory conditions. The proposed algorithm of video analysis has
      three looped stages: animal location tracking, detecting specific points in the
      region of interest, and estimation of temperature in these points. The presented
      method for measuring temperature of the biological object has the following
      advantage: it minimizes influence on the object of the interest, and thus allows
      clearer understanding of animal reaction to medication or treatment.

PMID- 29060107
TI  - Segmentation of gait sequences using inertial sensor data in hereditary spastic
      paraplegia.
AB  - Gait analysis is an important tool for diagnosis, monitoring and treatment of
      neurological diseases. Among these are hereditary spastic paraplegias (HSPs)
      whose main characteristic is heterogeneous gait disturbance. So far HSP gait has
      been analysed in a limited number of studies, and within a laboratory set up
      only. Although the rarity of orphan diseases often limits larger scale studies,
      the investigation of these diseases is still important, not only to the affect
      population, but also for other diseases which share gait characteristics.

PMID- 29060108
TI  - Effects of electrophysiological heterogeneity on vulnerability to re-entry in
      human ventricular tissue: A simulation study.
AB  - In this study, we constructed a two-dimensional ventricular tissue sheet with
      cellular electrophysiology modified from the Ten Tusscher 2006 Model.
      Heterogeneity was created by dividing the tissue into endocardium, midmyocardium
      and epicardium, further enhanced by a central ischemic zone. Subsequently, we
      investigated how electrophysiological heterogeneity affects re-entry initiation
      and maintenance in this tissue. Furthermore, we analyzed the vulnerable window
      (VW) under several conditions and concluded that heterogeneity across various
      myocardia expands the VW further than the monolayer myocardium model does.

PMID- 29060110
TI  - Replication of pressure-volume loop with controllable ESPVR and EDPVR curves on a
      personalized mock circulatory loop based on elastance function.
AB  - In the development of a left ventricular assist device (LVAD), it is important to
      evaluate the LVAD's hemodynamic effect on the compromised left ventricle (LV)
      before surgical implantation. The mock circulatory loop (MCL) is widely accepted
      as an in vitro test platform to evaluate LVADs across a wide range of operational
      conditions as a way to examine how the device and the cardiovascular system
      interact. Unfortunately, most MCLs represent an oversimplified model of cardiac
      function, with disease states simulated through generalized changes in heart rate
      and stroke volume. Because heart failure (HF) severity varies substantially among
      patients, an MCL is needed that can mimic the pressure-volume loop of an
      individual patient. In this work, two numerical elastance models, derived from a
      specific pressure volume loop template, were used to control the LV simulator of
      the MCL to simulate different degrees of HF. The numerical elastance model was
      then scaled to change the slopes of the end-systolic (ESPVR) and end-diastolic
      (EDPVR) pressure volume relationship curves to simulate systolic and diastolic
      dysfunction. The resulting experimental pressure volume loops are consistent with
      theoretical loops, demonstrating the feasibility of creating an MCL that can be
      customized for the patient.

PMID- 29060109
TI  - Physiologically motivated detection of Atrial Fibrillation.
AB  - Atrial Fibrillation (AF) is the most common arrhythmia and it is estimated to
      affect 33.5 million people worldwide. AF is associated with an increased risk of
      mortality and morbidity, such as heart failure and stroke and affects mostly
      older persons and persons with other conditions (e.g. heart failure and coronary
      artery disease). In order to prevent such life threatening and life quality
      reducing conditions it is essential to provide better algorithms, capable of
      being integrated in low-cost personalized health systems. This paper presents a
      new algorithm for AF detection, which is based on the analysis of the three
      physiological characteristics of AF: 1) Irregularity of heart rate and; 2)
      Absence of P-waves and 3) Presence of fibrillatory waves. Based on these
      characteristics several features were extracted from 12-lead electrocardiograms
      (ECG) and selected according to their discrimination ability. The classification
      between AF and non-AF episodes was performed using a Support Vector Machine (SVM)
      classification model. Our results show that the identification of the
      fibrillatory patterns, using the proposed features, extracted from the analysis
      of 12-lead ECG improves the performance of the algorithm to a sensitivity of
      88.5% and specificity 92.9%, when compared to our previous single-channel
      approach, in the same database.

PMID- 29060111
TI  - Real-time model-based control of afterload for in vitro cardiac tissue
      experimentation.
AB  - The performance of mechanical work by isolated cardiac muscle samples has
      typically been studied by subjecting their tissues to an isotonic shortening
      protocol, which results in "flat-topped" work-loop profiles. In order to better
      replicate the forces experienced by these tissues in vivo, we have developed a
      system for imposing a model-based, time-varying, load on isolated cardiac tissue
      preparations. A model of systemic afterload was developed from the combination of
      a Windkessel-type model of vascular fluid impedance, and the Laplace law of the
      heart, and encoded into a hardware-based control system. The model-predicted
      length change was then imposed on an isolated cardiac trabecula in a work-loop
      calorimeter, giving rise to force-length work-loops that more closely resemble
      those experienced by these tissues in vivo.

PMID- 29060112
TI  - Synergy of first principles modelling with predictive control for a biventricular
      assist device: In silico evaluation study.
AB  - Control for dual rotary left ventricular assist devices (LVADs) used as a
      biventricular assist device (BiVAD) is challenging. If the control system fails,
      flow imbalance between the systemic and the pulmonary circulations would result,
      subsequently leading to ventricular suction or pulmonary congestion. With the
      expectation that advanced control approaches such as model predictive control
      could address the challenges naturally and effectively, we developed a
      synergistic first principles model predictive controller (MPC) for the BiVAD. The
      internal model of the MPC is a simplified state-space model that has been
      developed and validated in a previous study. A single Frank-Starling (FS) control
      curve was used to define the target pump flow corresponding to the preload on
      each side of the heart. The MPC was evaluated in a validated numerical model
      using three clinical scenarios: blood loss, myocardial recovery, and exercise.
      Simulation results showed that the MPC was effective in adapting to changes in
      physiological states without causing ventricular suction or pulmonary congestion.
      The use of MPC for a BiVAD eliminates the need for two controllers of dual LVADs
      thus making the task of controller tuning easier.

PMID- 29060113
TI  - Monte Carlo method applied to the evaluation of the relationship between ejection
      fraction and its constituent components.
AB  - Ventricular function is routinely assessed by applying the clinically accepted
      metric ejection fraction (EF). The numerical value of EF depends on the interplay
      between end-systolic volume (ESV) and end-diastolic volume (EDV). The relative
      impact of the two constitutive components has received little attention.
      Pediatric cardiologists are interested in EF vs ESV when evaluating various
      congenital abnormalities. Following successful surgical intervention of Fallot
      tetralogy, many of these patients receive follow-up, not only during childhood,
      but also when being adults. Cardiologists diagnosing and treating elderly
      patients often analyze EF vs EDV, notably for phenotyping heart failure patients.
      Therefore, we study EF vs ESV as well as EF vs EDV in more detail. We explore the
      fundamentals of EF while analyzing a Fallot patient group. Three routes were
      followed, namely nonlinear regression, by implementing a Monte Carlo approach to
      generate EDV on the basis of known ESV values, and by using a theoretical
      graphical derivation. Our MRI-based post Fallot repair study includes left (LV)
      and right ventricular (RV) data (N=124). Using a robust approach we employed
      nonlinear regression with ESV as an independent variable. EDV was also assessed
      by Monte Carlo generated values for stroke volume within a physiological range.
      In all cases ESV emerges as the dominant component of EF, with less (P<;0.0001)
      impact of EDV. Using three independent routes we demonstrate that values for EF
      primarily depend on the corresponding ESV. This relationship is nonlinear, and
      correlation is always better with ESV compared to EDV in these patients, and
      confirmed in random number modeling studies.

PMID- 29060114
TI  - An in vitro study of the influence of monocusp patch size on the hemodynamics for
      reconstructing right ventricular outflow tract in tetralogy of Fallot.
AB  - For relief of right ventricular outflow tract obstruction in the operative
      treatment of tetralogy of Fallot and other complex congenital heart disease, it
      is often necessary to perform transannular monocusp patch to prevent right
      ventricular pressure overload and reduce pulmonary regurgitation. But the the
      geometric relationship between a monocusp patch length and the size of RVOT is
      not well defined. Five 20 mm sized monocusp patches were tested in simulated
      RVOTs which sized from 18 mm to 22 mm at 1 mm interval, respectively. The
      hydrodynamics of the patches were assessed through a quasi-physiological artery
      pulsatile flow duplicator system. The transvalvular pressure difference,
      effective orifice area and regurgitation flow were determined. The results showed
      that the regurgitation fraction increased with the diameter of RVOT increased
      (from 6.25% at 18 mm RVOT to 26.63% at 22 mm RVOT). Implant an oversized monocusp
      patch in RVOT reconstruction can effectively decrease the regurgitation but
      increase the transvalvular pressure and may reduce the longevity of leaflet.

PMID- 29060115
TI  - Sex-specific aspects of left and right ventricular volume regulation in patients
      following tetralogy of Fallot repair.
AB  - Ejection fraction (EF) is applied as a clinically relevant metric to assess both
      left (LV) and right ventricular (RV) function. EF depends on the interplay
      between end-systolic volume (ESV) and end-diastolic volume (EDV). The role of the
      two constitutive components is of particular interest for the follow-up study of
      Fallot patients at risk for RV volume overload. The volume regulation graph (VRG)
      relates ESV to EDV and has been advanced as a central tool to describe LV and RV
      function. The method permits additional analysis of the impact of clinically
      relevant determinants such as sex and age. Following Fallot repair and using MRI
      we evaluated LV and RV volumes in 124 patients (50 females), who were not taking
      any medication. Volumes were indexed for body surface area (BSA). The VRG
      regression lines are similar for both sexes, also when stratified for age (i.e.
      younger or older than 18 years), and different for LV and RV. However, RV ESV is
      larger (P=0.039) for adult males, as is RV EDV (P=0.026) in boys, relative to
      their female counterparts. For LV ESV we also found larger volumes, but only in
      boys (P=0.023) compared to girls. Average EF (only for RV) is lower in adult men
      compared to women (P=0.012), and to boys (P=0.007). These findings are partly in
      contrast with common observations made in individuals without a history of
      cardiac disease, where (with BSA indexation) LV and RV volumes are similar in
      children, but consistently larger in adult males. These results highlight the age
      and sex-specific volumetric aspects of remodeling following surgery in Fallot
      patients, and emphasize the pivotal role of ESV size in both RV and LV.

PMID- 29060116
TI  - Reliability evaluation of R-R interval measurement status for time domain heart
      rate variability analysis with wearable ECG devices.
AB  - Electrocardiograms (ECGs) captured by wearable ECG devices easily contain
      artifacts because of measurement faults. Since the frequency characteristics of
      artifacts are quite similar to those of R waves, it may result in R-R interval
      (RRI) miscalculations. To enable accurate heart rate variability (HRV) analysis
      in daily life, this paper proposes a method to reliably evaluate RRI measurement
      status, one that uses the electric potential characteristics of the QRS complex.
      Initial evaluation results show that it has the potential to distinguish
      miscalculated RRIs. Also proposed is a new RRI outlier exclusion method that uses
      the aforementioned method. Time domain measures of HRV derived from the proposed
      RRI outlier exclusion method are found to be more accurate than those derived
      from the conventional one.

PMID- 29060117
TI  - Real-time identification of heart rate responses via auxiliary-model-based damped
      RLS scheme.
AB  - This study was devoted to developing a new auxiliary-model-based damped recursive
      least squares (AMB-DRLS) by which the heart rate dynamics can be identified in a
      real-time manner. Unlike the current conventional schemes for heart rate dynamics
      modeling, the proposed scheme can simultaneously identify the HR response
      dynamics and compensate for the existing HR variability while it can also cope
      with the blowup phenomenon. The performance of the proposed AMB-DRLS scheme was
      experimentally verified using fifteen healthy male participants who performed
      treadmill trials following single-cycle square wave protocol. The obtained
      results revealed a significant difference in goodness-of-fit for the considered
      parameter estimation schemes. As a result, we conclude that the proposed AMB-DRLS
      method is able to identify the heart rate response dynamics in a real-time manner
      while preventing the blowup phenomenon.

PMID- 29060118
TI  - Simple and objective screening of major depressive disorder by heart rate
      variability analysis during paced respiration and mental task conditions.
AB  - Since objective biomarkers for major depressive disorder (MDD) are not readily
      available, clinical psychiatrists diagnose patients with MDD subjectively based
      on clinical interviews and diagnostic criteria. It often raises various concerns,
      including false responses by patients, subjective factors, and inexperience of
      the attendants leading to incorrect diagnosis. Here, we developed a self
      monitoring system for simple and objective screening of MDD using a
      photoplethysmography (PPG) sensor and a 24-GHz microwave radar, which was based
      on the analysis of heart rate variability (HRV) during paced respiration and
      mental task conditions. In our previous study, we assessed the reactivity of HRV
      measurements during a mental task (random number generation) condition in
      patients with MDD and healthy control subjects. The HRV indices are less reactive
      in patients with MDD compared to healthy subjects during the mental task, which
      enabled us to identify the patients at risk for depression. In this study, the
      reactivity of HRV was measured not only in the mental task but also during paced
      respiration (i.e., 5-s inhalation and 5-s exhalation) conditions, thereby
      assessing more detailed autonomic nervous system (ANS) activity via HRV indices.
      To investigate the effect of paced respiration on MDD screening, we compared the
      ANS activity via HRV indices in with/without paced respiration conditions in 28
      drug-naive patients with MDD and 27 healthy control subjects. The result showed
      that ANS significantly activated during the paced respiration condition
      (p<;0.05). The sensitivity in detecting patients with MDD was 86% under paced
      respiration and mental task conditions, which was higher than the sensitivity
      (68%) under mental task condition alone.

PMID- 29060119
TI  - The role of nonlinear coupling in Human-Horse Interaction: A preliminary study.
AB  - This study focuses on the analysis of human-horse dynamic interaction using
      cardiovascular information exclusively. Specifically, the Information Theoretic
      Learning (ITL) approach has been applied to a Human-Horse Interaction paradigm,
      therefore accounting for the nonlinear information of the heart-heart interplay
      between humans and horses. Heartbeat dynamics was gathered from humans and horses
      during three experimental conditions: absence of interaction, visual-olfactory
      interaction, and brooming. Cross Information Potential, Cross Correntropy, and
      Correntropy Coefficient were computed to quantitatively estimate nonlinear
      coupling in a group of eleven subjects and one horse. Results showed a
      statistical significant difference on all of the three interaction phases.
      Furthermore, a Support Vector Machine classifier recognized the three conditions
      with an accuracy of 90:9%. These preliminary and encouraging results suggest that
      ITL analysis provides viable metrics for the quantitative evaluation of human
      horse interaction.

PMID- 29060120
TI  - Heart rate variability analysis during muscle fatigue due to prolonged isometric
      contraction.
AB  - Fatigue can be defined as the muscular condition occurring before the inability
      to perform a task. It can be assessed through the evaluation of the median and
      mean frequency of the spectrum of the surface electromyography series. Previous
      studies investigated the relationship between heartbeat dynamics and muscular
      activity. However, exploitation of such cardiovascular measures to automatically
      identify muscle fatigue during fatiguing exercises is still missing. To this
      extent, HRV signals were gathered from 32 subjects during an isometric
      contraction task, and features defined in the time, frequency and nonlinear
      domains were investigated. We used surface electromyography to label the
      occurrence of muscle fatigue. Statistically significant differences were observed
      by comparing features related to fatigued subjects with the non-fatigued ones.
      Moreover, a pattern recognition system capable to achieve an average accuracy of
      78.24% was implemented. These results confirmed the hypothesis that a
      relationship between heartbeat dynamics and muscle fatigue might exist.

PMID- 29060121
TI  - Increased beat-to-beat variation in diastolic phase percentages in patients with
      congestive heart failure.
AB  - Diastolic time (DT) may reflect the functioning status of cardiac
      relaxation/diastolic filling. Previous studies shown that beat-to-beat variation
      in RR interval (i.e., HRV) is preferentially expressed in the variation in DT
      series, raising up a question that whether DT possesses intrinsic variation, or
      whether the DT variation is simply a surrogate of HRV without additional
      information. In this study, we defined the diastolic phase percentages (DP) by
      correcting DT by the corresponding RR interval and proposed to analyze DP
      variation (DPV) in order to eliminate the masking effect of HRV. We studied DPV
      of 60 patients with congestive heart failure (CHF) and 60 healthy control
      subjects. Radial artery pressure (RAP) was monitored in synchrony with
      electrocardiography (ECG) for 5 min in order to extract the proposed DPV.
      Additionally, DPV was corrected by the individual mean DP level which resulted in
      the coefficient of DPV (cDPV). The differences in DPV and cDPV between the two
      groups were determined by linear regression models controlled for age and sex.
      Results showed that both DPV and cDPV increased significantly in CHF patients
      compared with healthy control subjects (both p <; 0.05). Those results, highly
      endorsing the existence of intrinsic physiological variation in DT, may suggest
      that CHF patients have less stable cardiac relaxation (that is not due to HRV)
      or/and less stable contractility (since the diastolic and systolic phases are
      mutually complementary). This study may provide helpful reference for the
      noninvasive evaluation of cardiac functionality and for the further understanding
      of multiple physiological variabilities.

PMID- 29060122
TI  - Characterization and classification of patients with different levels of cardiac
      death risk by using Poincare plot analysis.
AB  - Cardiac death risk is still a big problem by an important part of the population,
      especially in elderly patients. In this study, we propose to characterize and
      analyze the cardiovascular and cardiorespiratory systems using the Poincare plot.
      A total of 46 cardiomyopathy patients and 36 healthy subjets were analyzed. Left
      ventricular ejection fraction (LVEF) was used to stratify patients with low risk
      (LR: LVEF > 35%, 16 patients), and high risk (HR: LVEF <= 35%, 30 patients) of
      heart attack. RR, SBP and TTot time series were extracted from the ECG, blood
      pressure and respiratory flow signals, respectively. Parameters that describe the
      scatterplott of Poincare method, related to short- and long-term variabilities,
      acceleration and deceleration of the dynamic system, and the complex correlation
      index were extracted. The linear discriminant analysis (LDA) and the support
      vector machines (SVM) classification methods were used to analyze the results of
      the extracted parameters. The results showed that cardiac parameters were the
      best to discriminate between HR and LR groups, especially the complex correlation
      index (p = 0.009). Analising the interaction, the best result was obtained with
      the relation between the difference of the standard deviation of the cardiac and
      respiratory system (p = 0.003). When comparing HR vs LR groups, the best
      classification was obtained applying SVM method, using an ANOVA kernel, with an
      accuracy of 98.12%. An accuracy of 97.01% was obtained by comparing patients
      versus healthy, with a SVM classifier and Laplacian kernel. The morphology of
      Poincare plot introduces parameters that allow the characterization of the
      cardiorespiratory system dynamics.

PMID- 29060123
TI  - A novel acoustic catheter stethoscope based acquisition and signal processing
      framework to extract multiple bio signals.
AB  - In this study, a novel acoustic stethoscope based on an intravenous catheter was
      introduced to measure vascular pressures from a Yorkshire pig. Our hypothesis is
      that by means of this single device (measurement system) and by applying signal
      analysis and processing framework, multiple vital bio signals can be extracted.
      In contrast, current conventional state-of-the-art technologies use multiple
      devices to provide the same information. The framework used to extract these bio
      signals consisted of a noise cancellation technique and wavelet based source
      separation. The preliminary results obtained from the acquired pressure data
      revealed the presence of acoustic heart and respiratory pulses. Finally, the
      computed heart and respiratory rates were benchmarked with actual values measured
      using conventional devices to validate our hypothesis.

PMID- 29060124
TI  - Tomographic particle image velocimetry for the validation of hemodynamic
      simulations in an intracranial aneurysm.
AB  - Image-based blood flow simulations can provide detailed hemodynamic information
      in diseased vessels such as intracranial aneurysms. However, validation is
      essential to evaluate the accuracy of these computations and further improve
      their acceptance among physicians. In this regard, tomographic particle image
      velocimetry was used to measure the flow characteristics in a patient specific
      aneurysm phantom model. Additionally, computational fluid dynamics (CFD)
      simulations were carried out using a well accepted commercial software package
      and a clinical research prototype, respectively. The comparison between in-vitro
      measurement and in-silico computations reveals a good qualitative agreement.
      Further, computations based on classical CFD agreed well with results from a
      clinical research prototype. Hence, the results of this study demonstrate the
      usability of numerical methods to obtain realistic blood flow predictions in a
      clinical context.

PMID- 29060125
TI  - In search for a better stent: Surrogate based multi-objective optimization of
      stent design under influence of vessel wall deformation.
AB  - Stenting is known as one of the main treatment procedure for some intravascular
      abnormalities such as stenosis and aneurysm. In recent years, stent optimization
      has been conducted by several research groups in order to increase its treatment
      efficacy. If we can observe post-deployment behavior on the blood vessel with
      respect to different stent designs, this observation will be useful in the design
      process. Kriging surrogate model based on fluid flow simulation on a deformed
      vessel wall was developed in order to observe this behavior. Multi-objectives
      optimization was performed with configurations of gap and size as design
      variables. In this research, percentage of low wall shear stress (WSS) area and
      average mechanical stress along the deployment area were set as the objective
      functions. We can recommend that strut with medium size around 100 - 250 micron
      with a relatively big inter-strut gap is suitable for achieving the optimize
      criteria. This is because on this range, acceptable optimized value of both
      objectives functions are successfully obtained.

PMID- 29060126
TI  - Computational estimation of the hemodynamic significance of coronary stenoses in
      arterial branches deriving from CCTA: A proof-of-concept study.
AB  - The development of non-invasive methods for the accurate hemodynamic assessment
      of the coronary vasculature has become a non-trivial matter for the everyday
      clinical practice. Virtual Functional Assessment Index has already been suggested
      as a valid alternative to the invasively measured FFR but only on coronary
      arterial segments. In this work, we propose a novel method for the estimation of
      the severity of coronary lesions in arterial branches from CCTA derived images.
      Four left arterial branches were reconstructed in 3D using our in-house developed
      3D reconstruction algorithm, and were subjected to computational blood flow
      simulations for the final calculation of the vFAI through the whole arterial
      branch. Strong correlation was found (r=0.82) between the two methods. A small
      relative error of 3.2% and a small trend of overestimation (0.023, SD=0.088) were
      also observed. All pathological cases presenting ischemia, were correctly
      discriminated by our method as hemodynamically significant lesions.

PMID- 29060127
TI  - Development of hand blood circulation measurement system for Raynaud syndrome
      using infrared imaging.
AB  - Raynaud syndrome refers to a medical condition where arterial smooth muscle
      contraction induces blood flow reduction. Thermal images and questionnaires have
      been used to assess the efficacy of treatment. In this research, a potential way
      to measure whole-hand blood circulation in real-time using infrared image is
      introduced. Normalized average pixel intensity of the regions of interest in hand
      was measured during or after blood circulation changes brought by temperature
      alteration and pressure applied to the hand or forearm. The intensity of regions
      has shown the tendency of the expected amount of blood in the hand in each blood
      circulation changes. Possible uses of this system are measuring severity of
      Raynaud syndrome and the efficacy of treatments.

PMID- 29060128
TI  - Acute effects of incremental exercise on central hemodynamics in young basketball
      athletes.
AB  - Acute effects of competitive sports on central hemodynamics are controversial.
      This study was aimed to evaluate acute effects of incremental exercise on central
      hemodynamics in young basketball athletes during 1-hour recovery. Fifteen young
      basketball athletes and fifteen controls underwent the acquisition of peripheral
      and central blood pressure before exercise and at 0, 5, 10, 15, 20, 30, 40, 50,
      60 min after incremental exercise. The incremental exercise was performed by
      Bruce test. Aortic systolic pressure (ASP), sub-endocardial viability ratio and
      stroke volume were significantly higher in athletes at all time points measured
      before and after exercise (P<;0.05). Heart rate and ejection duration were
      significantly lower in athletes (P<;0.01 for all). Augmentation index (AIx) was
      higher in athletes than that in controls at rest. AIx significantly reduced in
      athletes at 0 min after exercise (P<;0.01), but not in controls. Both Cardiac
      output and total peripheral resistance significantly changed in athletes at 0 min
      after exercise (P<;0.01). Cardiac functions to incremental exercise at all time
      points in basketball athletes are stronger than those in controls. However,
      potential mechanism of vascular functions should be further explored because
      basketball athletes have higher ASP and AIx than those in controls.

PMID- 29060129
TI  - IMU-based Real-time Pose Measurement system for Anterior Pelvic Plane in Total
      Hip Replacement Surgeries.
AB  - With the aging of population, the number of Total Hip Replacement Surgeries (THR)
      increased year by year. In THR, inaccurate position of the implanted prosthesis
      may lead to the failure of the operation. In order to reduce the failure rate and
      acquire the real-time pose of Anterior Pelvic Plane (APP), we propose a
      measurement system in this paper. The measurement system includes two parts:
      Initial Pose Measurement Instrument (IPMI) and Real-time Pose Measurement
      Instrument (RPMI). IPMI is used to acquire the initial pose of the APP, and RPMI
      is used to estimate the real-time pose of the APP. Both are composed of an
      Inertial Measurement Unit (IMU) and magnetometer sensors. To estimate the
      attitude of the measurement system, the Extended Kalman Filter (EKF) is adopted
      in this paper. The real-time pose of the APP could be acquired together with the
      algorithm designed in the paper. The experiment results show that the Root Mean
      Square Error (RMSE) is within 1.6 degrees, which meets the requirement of THR
      operations.

PMID- 29060130
TI  - Asthma Academy: Developing educational technology to improve Asthma medication
      adherence and intervention efficiency.
AB  - Asthma is a leading chronic disorder among children and adolescents. Although
      some children outgrow asthma while transitioning into adulthood, there are others
      who continue to suffer from life-threatening asthmatic exacerbations. Teenagers
      tend to have certain misconceptions about their asthmatic condition and treatment
      which are rarely recognized or addressed in regular clinical consultations. After
      reviewing the literature in this field, we have identified that improving patient
      knowledge can be effective in augmenting engagement, and considerably improving
      their clinical outcomes. It is necessary to develop an effective educational
      intervention that can help Asthma patients change their perception about self
      efficacy and ultimately reduce the total health care costs incurred. Hence, a
      sound transfer of knowledge during the transition from childcare to adult care is
      highly recommended. On these very lines, Georgia Institute of Technology designed
      an interactive educational application called Asthma Academy in conjunction with
      Children's Healthcare of Atlanta. This website resides in the public cloud and
      uses a novel animation video-based curriculum to deliver essential healthcare
      education to asthmatic adolescents in an interactive manner. What distinguishes
      it from similar initiatives is the use of a cost-effective technique to simulate
      caregiver-patient interactions and the ability to cater to a wide range of socio
      economic statuses and educational levels. A group-based study with twenty asthma
      adolescents was conducted to evaluate the user acceptance and performance of
      Asthma Academy supplemented by regular check-ups over a period of eight to ten
      weeks. Observations recorded post the study clearly indicate higher levels of
      engagement and the systematic dissemination of information offered by Asthma
      Academy.

PMID- 29060131
TI  - The first Transthyretin Familial Amyloid Polyneuropathy gait quantification study
      - preliminary results.
AB  - Transthyretin Familial Amyloid Polyneuropathy (TTR-FAP) is a rare neurological
      disease caused by a genetic mutation with a variable presentation and consequent
      challenging diagnosis, complex follow-up and treatment. At this moment, this
      condition has no cure and treatment options are under development. One of the
      disease's implications is a definite and progressive motor impairment that from
      the early stages compromises walking ability and daily life activities. The
      detection of this impairment is key for the disease onset diagnosis. With the
      goal of improving diagnosis of the symptoms and patients' quality of life, the
      authors have assessed the gait characteristics of subjects suffering from this
      condition. This contribution shows the results of a preliminary study, using a
      non-intrusive, markerless vision-based gait analysis tool. To the best of our
      knowledge, the reported results constitute the first gait analysis data of TTR
      FAP mutation carriers.

PMID- 29060132
TI  - Automatic positioning device for cutting three-dimensional tissue in living or
      fixed samples. Proof of concept.
AB  - The study and analysis of tissues has always been an important part of the
      subject in biology. For this reason, obtaining specimens of tissue has been vital
      to morphological and functionality research. Historically, the main tools used to
      obtain slices of tissue have been microtomes and vibratomes. However, they are
      largely unsatisfactory. This is because it is impossible to obtain a full, three
      dimensional structure of a tissue sample with these devices. This paper presents
      an automatic positioning device for a three-dimensional cut in living or fixed
      tissue samples, which can be applied mainly in histology, anatomy, biochemistry
      and pharmacology. The system consists of a platform on which the tissue samples
      can be deposited, plus two containers. An electromechanical system with motors
      and gears gives the platform the ability to change the orientation of a sample.
      These orientation changes were tested with movement sensors to ensure that
      accurate changes were made. This device paves the way for researchers to make
      cuts in the sample tissue along different planes and in different directions by
      maximizing the surface of the tract that appears in a slice.

PMID- 29060133
TI  - Comparison of the onset of uterine contractions determined from tocodynamometry
      and maternal perception.
AB  - The aim of this study was to investigate the time difference (TD) between the
      onset of uterine contraction (UC) determined from tocodynamometry (TOCO) and
      identified by maternal perception. The online available Icelandic database was
      used to calculate TD, which was defined as the difference between when it was
      felt by a pregnant woman and the starting point on the UC signal recorded by a
      TOCO. A total of 295 TDs from 78 recordings (from a total of 33 participants;
      among them, 13 participants included at least 3 recordings from different
      gestational weeks) were analyzed with the overall mean+/-SD of TD calculated. For
      each individual participant with at least 3 recordings, regression analysis was
      then performed to investigate the relationship between the mean TD from each
      recording with gestational week, with their overall slope calculated. The results
      showed that 85.4% of TDs was within [-40, 40] s, with an overall mean TD of 3.04
      s (p>0.05), indicating that there was no significant difference between the UC
      onset determined from TOCO and maternal perception. It was also noticed that
      61.5% recordings (48 out of 78 recordings) had all positive or negative TD for
      all the UCs analyzed within a recording. Furthermore, the regression analysis
      showed that the regression line slope was negative for 10 out of the 13
      participants with at least 3 recordings from different gestational weeks,
      resulting in that the overall slope (-2.85+/-5.58) was significantly negative
      (p<;0.05), and indicating that UC onset TD decreased with gestational weeks. In
      summary, this study quantitatively investigated the TD between the onset of UCs
      determined from TOCO and maternal perception, providing scientific evidence for
      future studies to understand the underlying mechanism of the time sequence of UC
      activity determined from different techniques.

PMID- 29060134
TI  - ARTSENS(r) orientation navigation system: A study towards faster arterial
      stiffness measurements.
AB  - ARTSENS(r) (ARTerial Stiffness Evaluation for Non-invasive Screening) is a
      technology for image-free evaluation of carotid artery stiffness with intelligent
      real time ultrasound signal processing algorithms for arterial wall
      identification and tracking. However, the influence of the ultrasound probe
      orientation on the clarity of the artery wall echoes makes measurement a
      challenge for inexperienced operators. We present an orientation navigation
      system (ONS), which performs real time tracking of the probe orientation and
      gives feedback to the user to help take faster readings with more ease for novice
      ARTSENS(r) operators. An controlled usability study on seven operators
      demonstrated that the ONS could reduce the average measurement time in ARTSENS(r)
      by nearly 50%. The usability of the system was rated positive with a score of
      75.4/100 and a grading of 8.3/10 by the operators. The ONS system makes
      ARTSENS(r) easier to operate thus enables it to be used for quick and reliable
      measurements in vascular screening scenarios.

PMID- 29060135
TI  - An electrical impedance tomography (EIT) multi-electrode needle-probe device for
      local assessment of heterogeneous tissue impeditivity.
AB  - Electrical Impedance Tomography (EIT) is an image reconstruction technique
      applied in medicine for the electrical imaging of living tissues. In literature
      there is the evidence that a large resistivity variation related to the
      differences of the human tissues exists. As a result of this interest for the
      electrical characterization of the biological samples, recently the attention is
      also focused on the identification and characterization of the human tissue, by
      studying the homogeneity of its structure. An 8 electrodes needle-probe device
      has been developed with the intent of identifying the structural inhomogeneities
      under the surface layers. Ex-vivo impeditivity measurements, by placing the
      needle-probe in 5 different patterns of fat and lean porcine tissue, were
      performed, and impeditivity maps were obtained by EIDORS open source software for
      image reconstruction in electrical impedance. The values composing the maps have
      been analyzed, pointing out a good tissue discrimination, and the conformity with
      the real images. We conclude that this device is able to perform impeditivity
      maps matching to reality for position and orientation. In all the five patterns
      presented is possible to identify and replicate correctly the heterogeneous
      tissue under test. This new procedure can be helpful to the medical staff to
      completely characterize the biological sample, in different unclear situations.

PMID- 29060136
TI  - Estimation of peripheral blood volume and interstitial volume in hemodialysis
      patients using bioimpedance techniques.
AB  - This paper describes a method to estimate interstitial fluid volume and
      peripheral blood volume (BVP) in hemodialysis (HD) patients using whole body
      (wBIS) and calf (cBIS) bioimpedance spectroscopy techniques. The aim of this
      study was to evaluate the usefulness of the technique. Thirty five HD patients
      were studied pre and post HD. Extracellular volume (ECV) and total body water
      (TBW) were measured using wBIS and cBIS. The calf resistances at 5 kHz (R5) and
      at 1000 kHz (R1000) respectively reflect ECV and TBW in the calf. A blood
      pressure cuff was placed over the area of cBIS. Regional and whole body plasma or
      BVP and interstitial (VIT) or total fluid volume are measured at R5 or R1000 when
      the cuff was inflated to just above the systolic blood pressure. According to
      calf normalized resistivity (CNR) post HD, patients were divided into two groups:
      overhydration (OH, CNR<;18.5, 10-2*Omegam3/kg) and normal hydration (NH,
      CNR>=18.5, 10-2*Omegam3/kg). BVP was higher in OH than in NH group which can be
      explained by the low ratio of change in VIT to ultrafiltration volume in the OH
      group (0.57+/-0.23 vs 0.83+/-0.45 L, p<;0.05). In conclusion, the method could be
      useful to better understand fluid dynamics during HD.

PMID- 29060137
TI  - Large dynamic range optical cavity based sensor using a low cost three-laser
      system.
AB  - An optical cavity based biosensor using a differential detection method has been
      proposed to provide a novel approach to point-of-care diagnostics. A two-laser
      based optical cavity based sensor system is designed and experimentally
      demonstrated. While the calculated differential value of the two-laser system
      shows larger responsivity compared to individual wavelengths, the dynamic range
      of the system is rather small. Because of that, it turned out its fabrication
      tolerance is also small based on the simulation. We employed a three-laser system
      and redesigned the optical cavity to increase the dynamic range and improve the
      fabrication tolerance. In this presentation, we report the measurement results of
      the three-laser system for the first time. This system increases the dynamic
      range threefold by a chaining action. Because of this large dynamic range, this
      three-laser system is anticipated to have a larger fabrication tolerance.

PMID- 29060138
TI  - Biomechanical procedure to assess sleep restriction on motor control and
      learning.
AB  - The analysis of sleep quality during long periods and its impact on motor control
      and learning performance are crucial aspects for human health. The aim of this
      study is to analyze effects of chronic sleep restriction on motor performance. It
      is intended to establish motor control indicators in sleep quality analysis. A
      wearable actigraphy that records accelerometry, ambient light, and body
      temperature was used to monitor the sleep habits of 12 healthy subjects for two
      weeks before performing motor control and learning tests. The day of the motor
      test, the subjects filled two questionnaires about the quality of sleep
      (Pittsburgh Sleep Quality Index - PSQI) and sleepiness (Epworth Sleepiness Scale 
      ESS). Afterwards they performed a coincident timing task that consisted of
      hitting a virtual target falling on the screen with the hand. An elbow flexion in
      the horizontal plane had to be performed on the correct time to reach the real
      target on a table at the same time as the virtual target on the screen. The
      subjects performed three sets of acquisition and transfer blocks of the
      coincident timing task. The subjects were clustered in two groups based on the
      PSQI and ESS scores. Actigraphy and motor control parameters (L5, correct
      responses, time variance) were compared between groups and experimental sets. The
      group with better sleep parameters did show a constant performance across blocks
      of task acquisition while the bad sleeper group improved from the first to the
      second acquisition block. Despite of this improvement, their performance is not
      better than the one of the good sleepers group. Although the number of subjects
      is low and it should be increased, these results indicate that the subjects with
      better sleep converged rapidly to a high level of performance, while the worse
      sleepers needed more trials to learn the task and their performance was not
      superior to the other group.

PMID- 29060139
TI  - A general descriptor for detecting abnormal action performance from skeletal
      data.
AB  - We propose an action-independent descriptor for detecting abnormality in motion,
      based on medically-inspired skeletal features. The descriptor is tested on four
      actions/motions captured using a single depth camera: sit-to-stand, stand-to-sit,
      flat-walk, and climbing-stairs. For each action, a Gaussian Mixture Model (GMM)
      trained on normal motions is built using the action-independent feature
      descriptor. Test sequences are evaluated based on their fitness to the normal
      motion models, with a threshold over the likelihood, to assess abnormality.
      Results show that the descriptor is able to detect abnormality with accuracy
      ranging from 0.97 to 1 for the various motions.

PMID- 29060140
TI  - Degree of RF MRI coil detuning for an anatomically realistic respiratory cycle
      modeled with the finite element method.
AB  - Respiratory motion is an important problem in Magnetic Resonance Imaging (MRI),
      contributing to image blurring during data acquisition and coil detuning. Using
      the concept of an ideal (perfectly matched and tuned at all available ports) RF
      transmit coil and the VHP-Female v4.0 dynamic CAD model, we numerically model and
      estimate the detuning of a full-body RF coil during the respiratory cycle.

PMID- 29060141
TI  - Design of the wearable device for hemiplegic gait detection using an
      accelerometer and a gyroscope.
AB  - Hemiplegic walking is the main symptom of hemiplegia and is the basis for judging
      the outcome or severity of hemiplegia. In this study, we developed a wearable
      measurement module for measuring the inertia signal generated during walking and
      evaluated the possibility of gait measurement as a basic study of the new
      hemiplegia diagnosis technology using wearable device. The developed measurement
      module is worn on the waist. It is equipped with 3-axis acceleration sensor and 3
      axis angular velocity sensor and has the function to transmit and record data
      through wireless communication. As a result of measuring the gait signals using
      the developed measurement module, specific patterns are shown for each axis
      according to each step, and it is confirmed that gait signals can be
      distinguished intuitively.

PMID- 29060142
TI  - Classification of voluntary coughs applied to the screening of respiratory
      disease.
AB  - Pulmonary and respiratory diseases (e.g. asthma, COPD, allergies, pneumonia,
      tuberculosis, etc.) represent a large proportion of the global disease burden,
      mortality, and disability. In this context of creating automated diagnostic
      tools, we explore how the analysis of voluntary cough sounds may be used to
      screen for pulmonary disease. As a clinical study, voluntary coughs were recorded
      using a custom mobile phone stethoscope from 54 patients, of which 7 had COPD, 15
      had asthma, 11 had allergic rhinitis, 17 had both asthma and allergic rhinitis,
      and four had both COPD and allergic rhinitis. Data were also collected from 33
      healthy subjects. These patients also received full auscultation at 11 sites,
      given a clinical questionnaire, and underwent full pulmonary function testing
      (spirometer, body plethysmograph, DLCO) which culminated in a diagnosis provided
      by an experienced pulmonologist. From machine learning analysis of these data, we
      show that it is possible to achieve good classification of cough sounds in terms
      of Wet vs Dry, yielding an ROC curve with AUC of 0.94, and show that voluntary
      coughs can serve as an effective test for determining Healthy vs Unhealthy
      (sensitivity=35.7% specificity=100%). We also show that the use of cough sounds
      can enhance the performance of other diagnostic tools such as a patient
      questionnaire and peak flow meter; however voluntary coughs alone provide
      relatively little value in determining specific disease diagnosis.

PMID- 29060143
TI  - Noninvasive evaluation of corneal viscoelasticity based on displacement in
      response to acoustic radiation force.
AB  - Noninvasive assessment of corneal mechanical properties in vivo will help to the
      understanding of the pathogenesis and early diagnosis of ectatic corneal
      disorders. This study presented a noninvasive method that assesses the corneal
      biomechanical properties by exciting the cornea with acoustic radiation force and
      monitoring its displacement using a dual-frequency confocal transducer. A 3.85
      MHz pushing element was used to induce localized tissue displacement, and the
      displacement was detected by the 12.8-MHz detecting elements using pulse-echo
      methods. Under constant acoustic radiation force, 0the tissue displacement are
      directly correlated with tissue biomechanical properties, a set of parameters
      were extracted from local displacement waveform, including relaxation time
      constant (tau), relative elasticity (RE) and relative viscosity (RV). In order to
      obtain corneal samples with different mechanical properties, the fresh bovine
      eyes were performed by collagen cross-linking (CXL). The result indicated that
      the estimated tau in untreated corneas were statistically significantly different
      (p<;0.05) from those of treated corneas and the estimation of tau varied
      significantly with different degrees of CXL. It is possible to develop a non
      invasive, effective and efficient method with high spatial resolution.

PMID- 29060144
TI  - The motion influence on respiration rate estimation from low-resolution thermal
      sequences during attention focusing tasks.
AB  - Global aging has led to a growing expectancy for creating home-based platforms
      for indoor monitoring of elderly people. A motivation is to provide a non
      intrusive technique, which does not require special activities of a patient but
      allows for remote monitoring of elderly people while assisting them with their
      daily activities. The goal of our study was to evaluate motion performed by a
      person focused on a specific task and check if this motion disrupts estimation of
      respiration rate. The preliminary results show that it is possible to reliable
      estimate respiration rate by focusing attention of a patient on a certain
      activity. The respiratory rate analyzed for silent reading task was estimated
      with mean error 0.27 breaths per minute (bpm), while for reading aloud task with
      1.18 bpm. The observed head motion during the reading aloud task was 1.5 higher
      that for silent reading and about two times smaller for a case in which subjects
      were not focused on any task.

PMID- 29060145
TI  - Electroencephalographic Neurofeedback to up-regulate frontal Theta rhythms:
      Preliminary results.
AB  - Retrieval of positive Autobiographical Memory (AM) has been reported to increase
      positive emotions in healthy population. Evidence suggests that positive AM
      retrieval tasks are correlated with synchronisation of frontal Theta rhythms (4
      8Hz). The present study has developed the Electroencephalography (EEG) based
      Neurofeedback (NF) protocols to promote voluntary elevation or up-regulation of
      positive AM retrieval related Theta rhythms over F3, Fz, F4 electrode sites (10
      20 System). The protocols were evaluated with a human participant in 10-day NF
      training. It observed that the average amplitude of observed Theta rhythms in
      each NF regulation block gradually increased over days of training and most was
      prominent at Fz electrode site. Furthermore, a larger peak at 6Hz was present in
      the spectrum of the observed Theta with later trial day suggesting up-regulation
      of Frontal Midline Theta (FmT) rhythms.

PMID- 29060146
TI  - Implementation of a manually operated blood pressure monitor based on energy
      harvesting for use in resource-constrained settings.
AB  - Health workers who screen for hypertension in rural and resource-constrained
      settings face many challenges including limited training, difficulties in
      correctly performing blood pressure (BP) measurements, and electrical grid
      unreliability. The aim of this study is to present the implementation of a
      manually operated BP monitor which assists health workers in overcoming some of
      these challenges by harvesting energy during manual cuff inflation and then
      discharging it in a controlled manner to power BP data acquisition, storage and
      wireless transmission. A prototype device was fabricated using a rotary
      alternator, flywheel and capacitor which harvests and stores energy when the bulb
      is squeezed during cuff inflation. Testing of the prototype revealed that an
      average of 1.55 J of energy can be scavenged during 30 s of cuff inflation. This
      is sufficient for BP data acquisition, storage and wireless transmission to a
      near-by smartphone even when accounting for losses.

PMID- 29060147
TI  - Facial geometry and speech analysis for depression detection.
AB  - Depression is one of the most prevalent mental disorders, burdening many people
      world-wide. A system with the potential of serving as a decision support system
      is proposed, based on novel features extracted from facial expression geometry
      and speech, by interpreting non-verbal manifestations of depression. The proposed
      system has been tested both in gender independent and gender based modes, and
      with different fusion methods. The algorithms were evaluated for several
      combinations of parameters and classification schemes, on the dataset provided by
      the Audio/Visual Emotion Challenge of 2013 and 2014. The proposed framework
      achieved a precision of 94.8% for detecting persons achieving high scores on a
      self-report scale of depressive symptomatology. Optimal system performance was
      obtained using a nearest neighbour classifier on the decision fusion of
      geometrical features in the gender independent mode, and audio based features in
      the gender based mode; single visual and audio decisions were combined with the
      OR binary operation.

PMID- 29060148
TI  - A novel approach for quantification of contour irregularities of diabetic foot
      ulcers and its association with ischemic heart disease.
AB  - Diabetic Foot Ulcer (DFU) is a common and global health problem in patients
      suffering from Diabetes. Delayed healing of these ulcers lead to serious
      problems, such as infection and amputation, apart from the problems faced in
      carrying out daily activities. This work has hypothesized the change in
      irregularity of wound contour may be linked to patient's clinical conditions. So
      far, fractal dimension is known to describe the change in irregularity of the
      fractal objects with change in scale but it fails to show any relation with the
      medical conditions in case of DFUs. This work introduces a new approach to
      quantify the irregularity of the wound contour and studies its association with
      some medical conditions. It was found that the change in irregularity of the
      wound contour from week 1 to week 4 had a close relation with ischemic heart
      disease as an important factor affecting the healing of DFUs.

PMID- 29060149
TI  - Estimates of peak electric fields induced by Transcranial magnetic stimulation in
      pregnant women as patients using an FEM full-body model.
AB  - Transcranial magnetic stimulation (TMS) for treatment of depression during
      pregnancy is an appealing alternative to fetus-threatening drugs. However, no
      studies to date have been performed that evaluate the safety of TMS for a
      pregnant mother patient and her fetus. A full-body FEM model of a pregnant woman
      with about 100 tissue parts has been developed specifically for the present
      study. This model allows accurate computations of induced electric field in every
      tissue given different locations of a shape-eight coil, a biphasic pulse, common
      TMS pulse durations, and using different values of the TMS intensity measured in
      SMT (Standard Motor Threshold) units. Our simulation results estimate the maximum
      peak values of the electric field in the fetal area for every fetal tissue
      separately and for the TMS intensity of one SMT unit.

PMID- 29060150
TI  - Electric field characteristics of low-field synchronized transcranial magnetic
      stimulation (sTMS).
AB  - Low-field synchronized trancranial magnetic stimulation (sTMS) was hypothesized
      to have significant therapeutic effects in patients with major depressive
      disorder by entrainment of neural oscillations. The sTMS device is comprised of
      neodymium magnets mounted over multiple brain regions and set to rotate at the
      patients alpha frequency. We characterized the electric field strength and
      distribution of sTMS using the finite element method. We found that the maximum
      induced electric field strength on the surfaces of the head and cortex are
      approximately 0.06Vm-1 and 0.02Vm-1, respectively. These field strengths are an
      order of magnitude lower than that delivered by transcranial current stimulation.

PMID- 29060151
TI  - Optimization of transcostal phased-array refocusing using sparse semidefinite
      relaxation method.
AB  - Treating tumors in organs shadowed by the ribs is a challenge for high intensity
      focused ultrasound (HIFU). The ribs absorb energy from the ultrasound beams
      causing their temperature to rise, while also distorting the beams, and limiting
      the target heat deposition. Accordingly, it is necessary to devise focusing
      methods that address the difficulties presented by the ribs. In this paper, a new
      approach that reduces total power deposition on the region of interest (ROI) by
      removing transducer elements is introduced. The method builds on the limited
      power deposition (LPD) method, which took advantage of the semidefinite
      relaxation (SDR) method to relax nonconvex constraints into convex form. The
      method introduced in this paper induces sparsity using the one-norm squared. The
      results of using this method to focus a 1-MHz spherical phased array on a target
      in an inhomogeneous medium are presented and compared to the ray tracing
      (shadowing) approach [1]. A finite-difference time domain propagation model was
      used to model the wave propagation to the target. Temperature simulations that
      utilized the inhomogeneous bioheat transfer equation (BHTE) illustrate the
      advantages of the induced sparsity LPD method. Together, these simulation results
      illustrate the advantages of using optimization based on sparsity inducing
      techniques over the shadowing approach.

PMID- 29060152
TI  - Personalization of a compartmental physiological model for an artificial pancreas
      through integration of patient's state estimation.
AB  - Artificial Pancreas (AP) are developed for patients with Type 1 diabetes. This
      medical device system consists in the association of a subcutaneous continuous
      glucose monitor (CGM) providing a proxy of the patient's glycaemia and a control
      algorithm offering the real-time modification of the insulin delivery with an
      automatic command of the subcutaneous insulin pump. The most complex algorithms
      are based on a compartmental model of the glucoregulatory system of the patient
      coupled to an approach of MPC (Model-Predictive-Control) for the command. The
      automatic and unsupervised control of insulin regulation constitutes a major
      challenge in AP projects. A given model with its parameterization on the shelf
      will not directly represent the patient's data behavior and the personalization
      of the model is a prerequisite before using it in a MPC. The present paper
      focuses on the personalization of a compartmental showing a method where taking
      into account the estimation of the patient's state in addition to the parameter
      estimation improves the results in terms of mean quadratic error.

PMID- 29060153
TI  - An adaptive DC-balanced and multi-mode stimulator IC with 1GOmega output
      impedance for compact electro-acupuncture system.
AB  - A compact and low-power electro-acupuncture (EA) IC and its Premeasurement System
      as off-chip board for verification are proposed for medical treatment and
      experiment. The multi-mode stimulator EA IC can perform adaptive charge balancing
      with various load condition as well as programmable supply voltage for 5
      different stimulation modes. The proposed EA IC occupies 2.2 mm * 1.5 mm
      including pads manufactured through 0.11 MUm 1P6M CMOS technology and dissipates
      1.8 mW at 1.2 V supply supporting 256 different current level with >1G output
      impedance. The Premeasurement System with corresponding specification to the
      proposed fabricated EA IC is fully implemented and tested on the human body and
      animal.

PMID- 29060154
TI  - Long term monitoring of a pressure ulcer risk patient using thermal images.
AB  - Patients in an immobile state are susceptible to pressure ulcers, which are
      localized injuries to the skin and/or underlying tissues due to prolonged
      pressure. This paper builds upon a body of work examining in-hospital older adult
      patients at-risk of developing pedal pressure ulcers by examining thermal images
      of one patient, who was reporting pain in her right foot, over 112 days of a
      hospital stay. Thermal images of the patient's left and right heels and malleoli
      were subjected to image processing to remove noise and enhance contrast, region
      selection and feature extraction to observe changes in temperature over time.
      Mean intensity within each ROI was extracted, and the difference in temperature
      between the left and right heels was calculated over time. The resulting
      temperature pattern was consistent with the physical phenomenon related to ulcer
      development, intervention and recovery; the right heel was similar in temperature
      when starting the study and at the end of the study, but was drastically warmer
      when experiencing erythema and drastically colder when experiencing ischaemia.
      These results suggest that consistent thermal imaging, in conjunction with image
      processing may be able to detect the formation of pressure ulcers faster than can
      be visually observed. Early detection of pressure ulcers is critical in the
      prevention of pressure ulcers, and is of great importance to any hospital or
      nursing home.

PMID- 29060155
TI  - Impact of injection time on migration of SPECT seizure onset in temporal lobe
      epilepsy.
AB  - In this work, we investigated an impact of injection time on migration of seizure
      onset in ictal/interictal single photon emission computed tomography (SPECT)
      study for patients with temporal lobe epilepsy. We selected 33 patients with
      refractory temporal lobe epilepsy who underwent ictal/interictal SPECT studies
      and had preoperative intracranial EEG result or surgical resection which was used
      as reference for seizure location. We divided all patients into two groups, which
      are the fast and the delayed groups; the delayed group comprised patients with
      injection time more than a cutoff time and vice versa. Using the subtraction
      ictal-interictal SPECT co-registered with SPECT (SISCOS) with varied Z-threshold
      (1.0, 1.5, 2.0 and 2.5), a method similar to subtraction ictal SPECT co
      registered to magnetic resonance imaging (MRI) (SISCOM), a seizure-onset region
      in the SISCOS image was localized at the region with maximum sum of Z-scores. For
      each pair of cutoff time and Z-threshold, we determined the migratory proportion
      which was defined as the proportion of patients whose seizure-onset location
      based on SISCOS image was discordant with the reference. At cutoff time of 32-35
      seconds and the Z-threshold of 2.0, the migratory proportion values were 7/26
      (26.9%) and 5/7 (71.4%) in the fast and the delayed groups, respectively. At the
      same range of cutoff time with the Z-threshold of 2.5, the migratory proportion
      was 8/26 (30.8%) in the fast group while the proportion was 5/7 (71.4%) in the
      delayed group. Using Fisher's exact test, the migratory proportion values at the
      Z-threshold of 2.0 and 2.5 were significantly different between the fast and the
      delayed groups (p = 0.0709 and 0.0838, respectively), suggesting that patients
      with temporal lobe epilepsy who undergo an ictal/interictal SPECT study with
      injection time longer than 35 seconds tend to have seizure-onset zone migration
      in the SISCOS analysis with the traditionally-used Z-threshold of 2.0.

PMID- 29060156
TI  - Automated Age-related Macular Degeneration screening system using fundus images.
AB  - This work proposed an automated screening system for Age-related Macular
      Degeneration (AMD), and distinguishing between wet or dry types of AMD using
      fundus images to assist ophthalmologists in eye disease screening and management.
      The algorithm employs contrast-limited adaptive histogram equalization (CLAHE) in
      image enhancement. Subsequently, discrete wavelet transform (DWT) and locality
      sensitivity discrimination analysis (LSDA) were used to extract features for a
      neural network model to classify the results. The results showed that the
      proposed algorithm was able to distinguish between normal eyes, dry AMD, or wet
      AMD with 98.63% sensitivity, 99.15% specificity, and 98.94% accuracy, suggesting
      promising potential as a medical support system for faster eye disease screening
      at lower costs.

PMID- 29060157
TI  - Multi-scale locally low-rank noise reduction for high-resolution dynamic
      quantitative cardiac MRI.
AB  - Evaluation of myocardial T1 times is conventionally limited to a single temporal
      snapshot of the cardiac cycle, leaving the dependence between functional and
      tissue characterization unexplored. We recently proposed a technique that
      alleviates this limitation by acquiring dynamic quantitative myocardial T1 maps.
      However, tradeoffs between temporal resolution, scan duration and SNR limit the
      spatial resolution. In this work, we propose a multi-scale locally low rank noise
      reduction approach without parameter-tuning to enable high acceleration rates in
      the acquisition, facilitating superior spatial and temporal resolutions in
      dynamic myocardial T1 mapping.

PMID- 29060158
TI  - Comparative analysis of different versions of a human model located inside a 1.5T
      MRI whole body RF coil.
AB  - Power deposition in tissues of a person subject to MRI examination is a
      significant point of concern today. Numerical electromagnetic simulation offers a
      way to model this complex problem with a sufficient degree of accuracy.
      Assessment of power deposition due to presence of implantable leads has been
      widely applied using the transfer function method. It relays on the incident
      tangential electric field (Etan) along the lead trajectory. This paper
      investigates how the precision of a numerical human model influences calculated
      Etan.

PMID- 29060159
TI  - Investigating the effect of coil model losses on computational electromagnetic
      exposure of an ASTM phantom at 64 MHz MRI.
AB  - The goal of this work is to investigate the effect of coil losses on the
      electromagnetic field generated in an ASTM phantom by a birdcage coil. The study
      was based on different numerical implementations of an RF body coil at 64 MHz,
      using the same 3D EM and RF circuit co-simulation procedure. The coil quality
      factor was evaluated with respect to losses due to power feed mismatch and to
      resistive losses of the coil components. The results of the study showed that the
      magnetic field at the coil iso-center, normalized to the square root of the whole
      body specific absorption rate, depends on the coil quality factor.

PMID- 29060160
TI  - Automatic fetal body and amniotic fluid segmentation from fetal ultrasound images
      by encoder-decoder network with inner layers.
AB  - This paper explores the effectiveness of applying a deep learning based method to
      segment the amniotic fluid and fetal tissues in fetal ultrasound (US) images. The
      deeply learned model firstly encodes the input image into down scaled feature
      maps by convolution and pooling structures, then up-scale the feature maps to
      confidence maps by corresponded un-pooling and convolution layers. Additional
      convolution layers with 1*1 sized kernels are adopted to enhance the feature
      representations, which could be used to further improve the discriminative
      learning of our model. We effectively update the weights of the network by fine
      tuning on part of the layers from a pre-trained model. By conducting experiments
      using clinical data, the feasibility of our proposed approach is compared and
      discussed. The result proves that this work achieves satisfied results for
      segmentation of specific anatomical structures from US images.

PMID- 29060161
TI  - Automatic identification of blood vessel cross-section for central venous
      catheter placement using a cascading classifier.
AB  - This paper presents a system that is able to automatically identify, segment, and
      track the cross-section of the internal jugular vein (IJV) and the common carotid
      artery (CCA) in an ultrasound image feed during a central venous catheter (CVC)
      placement procedure. The goal is to provide assistance to the practitioner in
      order to decrease the probability of complications stemming from inadvertent
      punctures of the CCA during the procedure. In the system, a modified Star
      algorithm is implemented to segment and track the blood vessel throughout an
      ultrasound video feed. A novel algorithm based on a cascading classifier is used
      to identify the location of the IJV and the CCA for two main tasks: (1) selecting
      the initial seed point at the start of tracking and (2) validating the
      segmentation results at each subsequent frame. The classifier uses shape features
      (vessel area, ellipse fitting error, vessel depth, vessel eccentricity) and pixel
      based features (pixel intensity and the histogram of oriented gradients
      descriptor) to differentiate between vessel and non-vessel structures and also
      differentiate between the IJV and the CCA. Evaluated on a database of 800
      ultrasound images containing the cross-section of both vessels, the cascading
      classifier was able to identify the IJV and the CCA in 92.25% and 85.13% of the
      images respectively without any initialization from the user at a maximum
      processing rate of 40.65 frames per second. This allows identification to be
      conducted in real-time with existing ultrasound machines.

PMID- 29060162
TI  - GPU-based computation for brain spatio-temporal networks definition.
AB  - Nowadays, with the increase of computational analysis in sciences such as biology
      and neuroscience, the computational aspect is one of the most challenging. The
      purpose of this work is the achieve the possibility to apply spatio-temporal
      networks inference techniques on brain to perform network analysis. One of the
      problems of spatio-temporal network applications is the computational time, and
      it becomes impractical to keep developing studies when it takes a long time to
      analyze and compute the results. We present a GPU-based system used to speed up
      the computation of spatio-temporal networks applied to different brain data;
      thanks to the architecture of these devices we are able to obtain an average
      increase in the performances of ~ 35* on a single GPU and ~ 78* on multi GPU with
      the respect of CPU execution.

PMID- 29060163
TI  - Automatic detection of Hyperreflective Foci in optical coherence tomography B
      scans using Morphological Component Analysis.
AB  - Hyperreflective Foci (HF) is one of the most common complications distributed in
      cross-sectional images of patients with Diabetic Macular Edema (DME). Scanning
      Laser Ophthalmoscope (SLO) images usually consists of several B-scans that
      represent a cross-sectional reconstruction of a plane through the anterior or
      posterior regions of retina. In each B-scan, HFs are geometrically distinct
      constituents in different retinal layers. Since the intensity levels of HFs and
      many other subjects in B-scans are the same, in this paper we try to separate HFs
      from other objects by detection of the point and curve singularities in each B
      scan. The decomposition algorithm presented in this paper is based on sparse
      image representation of B-scans using Morphological Component Analysis (MCA)
      technique. By using curvelet transform and Daubechies wavelet basis, two
      different over-complete dictionaries are constructed which represent two various
      aspects of B-scans. The HFs are more distinguished in reconstructed image with
      wavelet dictionary and other objects are mostly detectable by curvelet
      dictionary. So, HFs can be detected by applying an optimum threshold criterion on
      reconstructed image by wavelet atoms. Finally, the false positive points are
      reduced by removing the candidate points in RNFL and RPE layers, which are
      automatically segmented based on ridgelet transform. Our simulation results on
      1924 HFs show that sensitivity and specificity for HF detection is 91.0% and
      100%, respectively.

PMID- 29060164
TI  - Fibroatheroma identification in Intravascular Optical Coherence Tomography images
      using deep features.
AB  - Identifying vulnerable plaque is important in coronary heart disease diagnosis.
      Recent emerged imaging modality, Intravascular Optical Coherence Tomography
      (IVOCT), has been proved to be able to characterize the appearance of vulnerable
      plaques. Comparing with the manual method, automated fibroatheroma identification
      would be more efficient and objective. Deep convolutional neural networks have
      been adopted in many medical image analysis tasks. In this paper, we introduce
      deep features to resolve fibroatheroma identification problem. Deep features
      which extracted using four deep convolutional neural networks, AlexNet,
      GoogLeNet, VGG-16 and VGG-19, are studied. And a dataset of 360 IVOCT images from
      18 pullbacks are constructed to evaluate these features. Within these 360 images,
      180 images are normal IVOCT images and the rest 180 images are IVOCT images with
      fibroatheroma. Here, one pullback belongs to one patient; leave-one-patient-out
      cross-validation is employed for evaluation. Data augmentation is applied on
      training set for each classification scheme. Linear support vector machine is
      conducted to classify the normal IVOCT image and IVOCT image with fibroatheroma.
      The experimental results show that deep features could achieve relatively high
      accuracy in fibroatheroma identification.

PMID- 29060165
TI  - Exact localization of breakpoints of Retinal pigment epithelium in Optical
      Coherence Tomography of Optic Nerve Head.
AB  - Automatic segmentation of retinal boundaries in Optical Coherence Tomography
      (OCT) acquired around Optic Nerve Head (ONH) is of high importance, due to
      anatomical structure of this area. Exclusion of this area from calculations is a
      prevalent method but for cases like calculation of disc margins, it is not
      applicable. The pro-posed method is designed for exact localization of Retinal
      pigment epithelium break points in ONH centered OCTs. The method is based on
      incorporation of ridgelet transform for determination of the ONH region and
      consequent identification of the end points. Incorrect localization in presence
      of shadow of retinal vessels has also been considered to obtain the high
      accuracy. Considering the mean value of disk diameter (145.07+/-38.96), the
      rational error of the algorithm is 0.07.

PMID- 29060166
TI  - The analysis of eye blinking pattern using high-frame-rate camera.
AB  - The purpose of this study is to analyze eye blinking patterns using high-speed
      camera without additional instructions and illuminations. The experimental video
      clips are taken at 240 frames per second, which is twice the flickering rate of
      room light. The eye blinking sequences are segmented from the whole video clip
      after reducing noise and baseline wander. The shapes and positions of the upper
      eyelid in blinking sequences are evaluated by a polynomial curve fitting
      algorithm and visualized to the eyelid position graph. The graph made it easy to
      recognize the eye blinking patterns. In order to analyze patterns, eye blinking
      parameters are calculated, and an eye blinking cycle is divided into three phases
      as 'Closing phase', 'Closed phase', and 'Opening phase'. In the experiments with
      forty volunteers, proposed method can analyze eye blinking patterns
      qualitatively.

PMID- 29060167
TI  - Blood oxygenation changes resulting from subthreshold high frequency repetitive
      transcranial magnetic stimulation.
AB  - Effects of high frequency repetitive transcranial magnetic stimulation (rTMS)
      with a subthreshold intensity on hemodynamic response in brain cortices (both
      motor and prefrontal cortices) was investigated using the functional near
      infrared spectroscopy (fNIRS) technique. FNIRS signals of the motor and
      prefrontal cortices were acquired in healthy volunteers (n=7) at rest and during
      rTMS intervention. A significant reduction in oxygenated hemoglobin (HbO)
      concentration during the entire stimulation process was observed from both motor
      and prefrontal cortices. Results showed that the fNIRS technique can provide a
      reliable measure of regional cortical brain activation that could be valuable in
      studying cortical excitability connectivity in combination with rTMS.

PMID- 29060168
TI  - Recognition of protozoan parasites from microscopic images: Eimeria species in
      chickens and rabbits as a case study.
AB  - Automated diagnosis and identification of diseases and conditions such as
      parasites from microscopic images have been mainly carried out by utilizing the
      object morphological characteristics. The extraction of morphometric features
      needs the use of highly complex techniques that require computational power.
      Therefore, in order to reduce this complexity, this paper presents an automated
      identification based on analyzing three groups of pixel-based feature sets:
      column features (CF), row features (RF), and the third one (CRF) obtained by
      merging CF and RF together. For the classification task, K-Nearest Neighbor (KNN)
      and Artificial Neural Networks (ANN) have been applied. The classification
      results have been evaluated by adapting a 5-fold cross validation. Additionally,
      a robust sub-set of the features has been selected by Relieff feature selection
      method to prevent overfitting, which in turn has improved the final results. Two
      microscopic image slide databases of a type of protozoan parasites genus called
      Eimeria in fowls and rabbits have been examined in order to assess the robustness
      of the proposed methods. The highest accuracy rates obtained when the entire
      features were used are 85.55% (+/-0.39%) and 96.6% (+/-0.82%) from grey-scale
      level and color images, respectively. These results have been increased by 5%
      when the feature size is reduced by two thirds when Relieff was utilized. The
      feature sets have yielded highly accurate results and are expected to make the
      automatic identification simpler than the analysis of morphological features.

PMID- 29060169
TI  - Development and validation of a computational simulator for pediatric acute
      respiratory distress syndrome patients.
AB  - This paper presents the adaptation of an advanced cardiorespiratory model of
      acute respiratory distress syndrome in adult patients to pediatric
      pathophysiology. We describe how model equations and parameters were revised to
      represent the physiological characteristics of pediatric Acute Respiratory
      Distress Syndrome (ARDS) patients. The adapted model was matched to data from
      twelve mechanically ventilated patients diagnosed with Pediatric Acute
      Respiratory Distress Syndrome (PARDS), and was shown to reproduce the available
      clinical data accurately for all patients. This new model constitutes the first
      detailed computational simulator specifically tailored to PARDS patients, and can
      be used as an investigational tool for developing and evaluating novel
      therapeutic strategies.

PMID- 29060170
TI  - Nonparametric modelling of VO2 response to exercise.
AB  - This paper investigates the modelling of oxygen consumption (VO2) response to
      jogging exercise on treadmill. Unlike most of the previous methods, which often
      use simple parametric models, e.g., first order linear time invariant model, this
      study applied a nonparametric kernel based regularised method to estimate VO2 to
      address the ill-conditioned modelling problem and achieve accurate estimation. In
      particular, it is worthy to be noted that the selection of kernels will affect
      the results for different modelling scenarios. Therefore, in this research, both
      radial basis kernel and stable spline kernel were selected for testing. In order
      to select the favourable kernel for this system, a simulation related to VO2
      jogging speed was carried out. The results of simulation indicated that spline
      kernel can achieve higher accuracy comparing to radial basis function kernel.
      Experimentally, the kernel based estimation method and spline kernel were tested
      using six participants. From the results, an average impulse response is
      obtained. It showed the VO2 estimation, based on the average finite impulse
      response, is fitted well to the six observations collected from the participants.

PMID- 29060171
TI  - Development of a real-time breathing-rate monitor using difference operation
      method and adaptive windowing on dry-electrode ECG signal.
AB  - Estimation of breathing rate (BR) along with electrocardiogram signal plays an
      important role in patient health monitoring. Continuous monitoring of BR is often
      required during diagnosis of many diseases. Traditional methods like nasal air
      flow equipments employ cumbersome methods of BR monitoring which is not suitable
      for continuous monitoring. Therefore, a non-invasive method of estimation is
      required. This paper proposes a non-invasive way of BR estimation using dry
      electrode ECG from the palm of a person. The paper uses Respiratory Peak
      Arrhythmia and Respiratory Sinus Arrhythmia based ECG derived respiratory rate
      estimation technique. We have developed an algorithm for real-time BR estimation
      which can be run on embedded platform having limited computation capability. The
      whole algorithm was first tested on MIT-BIH polysomnographic database and then
      later extended to obtained signal from developed analog circuitry and the
      embedded platform. Nasal airflow sensor is used for calculating reference BR. The
      developed setup was tested on volunteers and the obtained results show accuracy
      to be in between 2 breaths per minutes.

PMID- 29060172
TI  - Monitoring of nocturnal central sleep apnea in Heart failure patients using
      noncontact respiratory differences.
AB  - Monitoring of respiration patterns allows the early detection of various
      breathing disorders and may better identify those at risk for adverse acute
      outcomes in a variety of clinical settings. In this paper, we report on the use
      of SleepMinder (SM), a bedside non-contact Doppler-based biomotion recording
      sensor, to monitor remotely the nocturnal respiration patterns of 50 patients
      with systolic Heart failure (HF) while undergoing a lab based Polysomnography
      (PSG) test. A new respiration rate (RR) monitoring algorithm was developed based
      on the collected overnight radar signals. Two schemes of RR scoring were
      utilized: respiratory rate count (RRC) and instantaneous respiratory rates (IRR).
      Analysis of SM vs. PSG revealed that the mean/median IRR scored by SM is highly
      correlated with that scored on the nasal flow/effort signals from the
      corresponding PSG studies on all patients, with a significant correlation
      coefficient of 0.98 (average absolute difference of 0.31 breaths/min), and 0.97
      (p<;0.01, average absolute difference of 0.38 breaths/min) for the median and
      mean of RR respectively. Our experimental results also show that the difference
      between the RR estimations from IRR and RRC schemes can be utilized to identify
      central sleep apnea (CSA)/Cheyne-Stokes respiration (CSR) sections without
      additional apnea detection modules. As a result, with a sensitivity and
      specificity of 71% and 88% respectively, and an accuracy of 86%, our CSA/CSR
      screener, plugged with our RR estimation, can play an important role in the
      remote management of HF patients.

PMID- 29060173
TI  - Relationship between heart rate excursion and apnea duration in patients with
      Obstructive Sleep Apnea.
AB  - Obstructive Sleep Apnea (OSA) is a sleep disorder with a high prevalence in the
      general population. It is a risk factor for many cardiovascular diseases, and an
      independent risk factor for cerebrovascular diseases such as stroke. After an
      apnea episode, both arterial blood pressure and cerebral blood flow velocity
      change in function of the apnea duration (AD). We hypothesized that the relative
      excursion in heart rate (AHR), defined as the percentage difference between the
      maximum and the minimum heart rate values associated to an obstructive apnea
      event, is also related to AD. In this work we studied the relationship between
      apnea-related AHR and AD in a population of eight patients with severe OSA. AHR
      and AD showed a moderate but statistically significant correlation (p <; 0.0001)
      in a total of 1454 obstructive apneas analyzed. The average heart rate excursion
      for apneas with AD >= 30s (DeltaHR = 31.29 +/- 6.64%) was significantly greater
      (p = 0.0002) than for apneas with AD ? [10,20)s (DeltaHR = 18.14+/-3.08%). We
      also observed that patients with similar Apnea-Hypopnea Index (AHI) may exhibit
      remarkably different distributions of AHR and AD, and that patients with a high
      AHI need not have a higher average AHR than others with a lower severity index.
      We conclude that the overall apnea-induced heart rate excursion is partially
      explained by the duration of apnoeic episodes, and it may be a simple measure of
      the cardiovascular stress associated with OSA that is not directly reflected in
      the AHI.

PMID- 29060174
TI  - Characterization of a tooth microphone coupled to an oral appliance device: A new
      system for monitoring OSA patients.
AB  - Obstructive sleep apnea (OSA) is a highly prevalent chronic disease, especially
      in elderly and obese populations. Despite constituting a serious health, social
      and economic problem, most patients remain undiagnosed and untreated due to
      limitations in current equipment. In this work, we propose a novel method to
      diagnose OSA and monitor therapy adherence and effectiveness at home in a non
      invasive and inexpensive way: combining acoustic analysis of breathing and
      snoring sounds with oral appliance therapy (OA). Audiodontics has introduced a
      new sensor, a tooth microphone coupled to an OA device, which is the main pillar
      of this system. The objective of this work is to characterize the response of
      this sensor, comparing it with a commercial tracheal microphone (Biopac
      transducer). Signals containing OSA-related sounds were acquired simultaneously
      with the two microphones for that purpose. They were processed and analyzed in
      time, frequency and time-frequency domains, in a custom MATLAB interface. We
      carried out a single-event approach focused on breaths, snores and apnea
      episodes. We found that the quality of the signals obtained by both microphones
      was quite similar, although the tooth microphone spectrum concentrated more
      energy at the high-frequency band. This opens a new field of study about high
      frequency components of snores and breathing sounds. These characteristics,
      together with its intraoral position, wireless option and combination with
      customizable OAs, give the tooth microphone a great potential to reduce the
      impact of sleep disorders, by enabling prompt detection and continuous monitoring
      of patients at home.

PMID- 29060175
TI  - Characterization of microphones for snoring and breathing events analysis in
      mHealth.
AB  - Obstructive sleep apnea (OSA) is one of the most common sleep disorders,
      especially in elderly population. Despite its high prevalence and severe
      consequences, most patients remain undiagnosed due to serious limitations on the
      existing equipment. Efforts are being done to find cost-effective alternatives
      and mHealth solutions could play a key role. One promising approach in this
      context is the acoustic analysis of snoring. The sensor it requires is a
      microphone, which is widely available in different models and even integrated in
      smartphones. The objective of this work is to characterize and compare the
      responses of two commercial tracheal microphones and a mHealth-based microphone,
      as a proof-of-concept to evaluate their potential as sensors for OSA detection.
      To do that, we designed an experimental protocol to study OSA-related events
      (breaths, snores and apneas) simulated by 4 subjects. Test signals were
      simultaneously recorded with different microphones and posteriorly processed and
      analyzed. We accurately characterized the frequency response of the two
      commercial microphones, finding that one of them was too restrictive (bandwidth
      50-250 Hz) and thus not suitable as snoring sensor for high-frequency acoustic
      analysis. Regarding smartphones, we studied the Samsung Galaxy S5 microphone. We
      found that, when located over the thorax, it provided quality signals comparable
      to those of tracheal microphones, with a broader frequency response. Further work
      is required, but this preliminary study suggests that acoustic analysis of
      snoring through mHealth solutions can be a feasible alternative to screen and
      monitor OSA patients at home.

PMID- 29060176
TI  - Sleep apnoea diagnosis using respiratory effort-based signals - a comparative
      study.
AB  - A measure of the respiratory effort during a sleep study is an important
      contributor to the diagnosis of sleep apnoea. A common way of measuring
      respiratory effort is with bands with stretch sensors placed around the chest
      and/or abdomen. An alternative, and more convenient method from the patient's
      perspective, is via the ECG derived respiration (EDR) signal which provides an
      estimate of the respiratory effort at each heartbeat. In this study we performed
      a side-by-side comparison of the discrimination information for identifying
      epochs of sleep apnoea contained in the chest respiratory effort signal and three
      methods of calculating the EDR signal. Using simultaneously recorded chest band
      and ECG signals extracted from overnight polysomnogram (PSG) data from 8 subjects
      (4 controls, 4 apnoeas. MIT PhysioNet Apnea-ECG database), we extracted identical
      features from the two sensors and used the features to train a linear
      discriminant classifier to classify one-minute epochs as being apneic or normal.
      Ground truth labelling of each epoch was achieved with an expert using the full
      PSG as a reference. Our cross validation results revealed that the full
      respiratory effort signal resulted in an accuracy of 87% in correctly identifying
      the epoch label. When the respiratory signal was resampled at each heartbeat (as
      occurs with the EDR signal) the accuracy was 86%, suggesting that the sampling
      process inherent to the EDR signal does not materially affect its discrimination
      ability. The best EDR method was based on the calculating the QRS area for every
      heart and achieved an accuracy of 81%. Our results suggest that, while there is
      some information loss in the EDR estimation process, the EDR signal is a
      convenient and useful signal for sleep apnoea diagnosis.

PMID- 29060177
TI  - mHealth tools for monitoring Obstructive Sleep Apnea patients at home: Proof-of
      concept.
AB  - Obstructive Sleep Apnea (OSA) is a sleep disorder that affects mainly the adult
      and elderly population. Due to the high percentage of patients who remain
      undiagnosed and untreated because of limitations of current diagnosis methods,
      the management of OSA is an important social, scientific and economic problem
      that will be difficult to be assumed by health systems. On the other hand,
      smartphone platforms (mHealth systems) are being considered as an innovative
      solution, thanks to the integration of the essential sensors to obtain clinically
      relevant parameters in the same device or in combination with wireless wearable
      devices.

PMID- 29060178
TI  - Causal brain-heart information transfer during visual emotional elicitation in
      healthy subjects: Preliminary evaluations and future perspectives.
AB  - Complex heartbeat dynamics is known to reflect subject's emotional state, thanks
      to numerous links to brain cortical and subcortical regions. Likewise, specific
      brain regions are deeply involved in vagally-mediated emotional processing and
      regulation. Nevertheless, although the brain-heart interplay has been studied
      during visual emotion elicitation, directional interactions have not been
      investigated so far. To fill this gap, in this study we investigate brain-heart
      dynamics during emotional elicitation in healthy subjects through measures of
      Granger causality (GC) between the two physiological systems. Data were gathered
      from 22 healthy volunteers who underwent pleasant/ unpleasant affective
      elicitation using pictures from the International Affective Picture System.
      Neutral emotional stimuli were elicited as well. High density
      electroencephalogram (EEG) signals were processed to obtain time-varying maps of
      cortical activation, whereas the associated instantaneous cardiovascular dynamics
      was estimated through inhomogeneous point-process models. Concerning the
      information transfer brain-to-heart, GE highlighted significant valence-dependent
      lateralization with respect to resting states. Furthermore, as a proof of
      concept, the study of heart-to-brain dynamics considering EEG oscillations in the
      gamma band (30-45 Hz) highlighted differential information transfer between
      neutral and positive elicitations directed to the prefrontal cortex.

PMID- 29060179
TI  - Information transfer and information modification to identify the structure of
      cardiovascular and cardiorespiratory networks.
AB  - To fully elucidate the complex physiological mechanisms underlying the short-term
      autonomic regulation of heart period (H), systolic and diastolic arterial
      pressure (S, D) and respiratory (R) variability, the joint dynamics of these
      variables need to be explored using multivariate time series analysis. This study
      proposes the utilization of information-theoretic measures to measure causal
      interactions between nodes of the cardiovascular/cardiorespiratory network and to
      assess the nature (synergistic or redundant) of these directed interactions.
      Indexes of information transfer and information modification are extracted from
      the H, S, D and R series measured from healthy subjects in a resting state and
      during postural stress. Computations are performed in the framework of
      multivariate linear regression, using bootstrap techniques to assess on a single
      subject basis the statistical significance of each measure and of its transitions
      across conditions. We find patterns of information transfer and modification
      which are related to specific cardiovascular and cardiorespiratory mechanisms in
      resting conditions and to their modification induced by the orthostatic stress.

PMID- 29060180
TI  - Functional connectivity analysis of multiplex muscle network across frequencies.
AB  - Physiological networks reveal information about the interaction between
      subsystems of the human body. Here we investigated the interaction between the
      central nervous system and the musculoskeletal system by mapping functional
      muscle networks. Muscle networks were extracted using coherence analysis of
      muscle activity assessed using surface electromyography (EMG). Surface EMG was
      acquired from 36 muscles distributed throughout the body while participants were
      standing upright and performing a bimanual pointing task. Non-negative matrix
      factorization revealed functional connectivity in four frequency bands. The
      spatial arrangement differed considerably across frequencies supporting a
      multiplex network organisation. Graph-theory analysis of layer-specific network
      revealed a consistent fat-tail distribution of the edges weights, distinct
      efficiency values, and core-periphery properties. These frequency bands may be
      spectral fingerprints of different neural pathways that innervate the spinal
      motor neurons to control the musculoskeletal system.

PMID- 29060181
TI  - A new hand function assessment method using an infrared imaging device.
AB  - Many post-stroke patients suffer various degrees of hand function and fine motor
      skills impairment. Both passive and active hand rehabilitation training are
      beneficial in improving strength and dexterity of hands. However, hand
      rehabilitation programs should be prescribed, based on an accurate assessment of
      hand function. Here we propose a novel method for hand function assessment that
      can accurately measure multiple joint angles of a hand simultaneously using a
      portable infrared imaging device. Different from the traditional assessment
      methods that are often based on clinicians' subjective observation and ordinal
      charts, this method provides an accurate, fast and objective evaluation using
      infrared imaging sensors. This novel hand function assessment method can be used
      to replace the currently popularly used traditional method for fine hand function
      modeling and assessment in rehabilitation medicine and can play an important role
      in precision post-stroke function analysis.

PMID- 29060182
TI  - Frequency-range optimized preprocessing methods for quantitative analysis of
      glucose in blood serum from broadband dielectric spectra.
AB  - This paper presents the results of combining scatter correction and spectral
      derivation preprocessing methods with frequency-range optimization to improve the
      accuracy of blood glucose concentration prediction when using a Partial Least
      Square Regression model. Using broadband dielectric spectroscopy, absorption
      spectrums in the frequency range of 500 MHz to 50 GHz were gathered from blood
      serums. Partial Least Square Regression models were trained using data gathered
      from samples of varying glucose concentrations and temperatures, and the quality
      of the predictions were evaluated by performing leave-one-out cross validation.
      Potential improvements in prediction accuracy were assessed by finding the
      optimal frequency ranges of dielectric absorption spectrums through iteration, in
      addition to treatments using common preprocessing methods. The most effective
      combination of preprocessing method and its corresponding characteristic
      frequency range was determined from validation using several samples. Finally,
      among all the preprocessing methods and the frequency ranges explored, performing
      Savitzky-Golay filtering without derivations lowered the average root mean
      squared error amongst all the samples from 172 mg/dL without preprocessing, to
      143 mg/dL. Additionally, by focusing on a specific frequency range, the root mean
      squared error dropped to 80.2 mg/dL.

PMID- 29060183
TI  - Three-dimensional Electrodes formation using liquid metal in micro channels for 3
      axis Capacitive Force Sensor.
AB  - In this study, we propose three-dimensional formation of electrodes made of
      liquid metal. First, three-dimensional micro channels are formed by stacking PDMS
      layers. Second, liquid metal, galinstan, is introduced into the channels to form
      electrodes and wirings. This process is crucial to develop miniaturized 3-axis
      capacitive force sensor. In our previous work, we proposed a ball-point-pen like
      capacitive sensor, however, it was difficult to be miniaturized to be mounted
      onto an endoscope retaining the function. We successfully manufactured 3-axis
      cylindrical capacitive force sensor, 5 mm in diameter and small enough to be
      mounted onto an endoscope. We experimentally characterized the sensor. The
      proposed and demonstrated sensor can be readily applicable for endoscopic
      palpation.

PMID- 29060184
TI  - Monitoring voluntary blink magnitude through a wearable eye-tracking system: A
      preliminary study.
AB  - This study proposes a novel approach to measure the contractile force of eye
      blink that is generally obtained from the orbicularis oculi activity through
      Ocular ElectroMyo-Graphy (O-EMG). Here, O-EMG is compared with the eye
      information acquired through a wearable head-mounted eye-tracking system in order
      to investigate the possibility of using the eye-tracking in place of the O-EMG.
      Eight subjects were simultaneously monitored through an O-EMG and the eye-tracker
      while they were performing a structured protocol implying a variation in the
      blink contractile strength. Results showed that eye-tracking features were able
      to statistically discriminate three kinds of contractile forces similarly to EMG
      features. The consequent correlation analysis revealed that all the EMG-related
      features were significantly correlated with the eye-tracking ones with a p-value
      <;10-6. Moreover, considering the extracted eye-tracking features, i.e.
      Integrated Gaze Path (IGP) and Eye-closed Duration (ECD), IGP reported a higher
      Spearman's correlation values with eye-blink reflex magnitude (EBM) than ECD.
      These encouraging results suggest that the ocular information extracted from the
      eye-tracking could be profitably used in non-invasive ecological environments
      where wearability and comfortability play a crucial role in detecting spontaneous
      response.

PMID- 29060185
TI  - Can accelerometry data improve estimates of heart rate variability from wrist
      pulse PPG sensors?
AB  - A key prerequisite for precision medicine is the ability to assess metrics of
      human behavior objectively, unobtrusively and continuously. This capability
      serves as a framework for the optimization of tailored, just-in-time precision
      health interventions. Mobile unobtrusive physiological sensors, an important
      prerequisite for realizing this vision, show promise in implementing this quality
      of physiological data collection. However, first we must trust the collected
      data. In this paper, we present a novel approach to improving heart rate
      estimates from wrist pulse photoplethysmography (PPG) sensors. We also discuss
      the impact of sensor movement on the veracity of collected heart rate data.

PMID- 29060186
TI  - Flexible sensor sheet for real-time pressure monitoring in artificial knee joint
      during total knee arthroplasty.
AB  - As described in this paper, we propose a sheet-type pressure sensor to support
      assistive technology for artificial knee joint replacement. The proposed pressure
      sensor consists of two sheets: an electrode sheet with metal wiring and a
      flexible polymer-based insulating layer on 80 MUm polyimide film, as well as a
      pressure-sensitive conductive sheet that can function as a pressure-to-resistance
      sensor. We developed a 5 cm * 7 cm pressure sensor sheet with 116 sensing points.
      The multiple sensing sheet is expected to monitor the pressure distribution in an
      artificial knee joint during total knee arthroplasty to improve patients' quality
      of life.

PMID- 29060187
TI  - Micro-patterned films of bio-functionalized conducting polymers for cellular
      engineering.
AB  - Conducting polymers (CPs) are easy to process and have tunable physical and
      chemical properties including conductivity, volume, color, and hydrophobicity.
      Therefore, these organic polymers are attractive in a broad spectrum of
      bioelectronic applications ranging from implantable electrodes to biosensors and
      actuators. Patterned films of CPs, especially with various surface chemistries,
      provide versatile and sophisticated building-blocks for bioelectronics. In this
      context, we recently introduced a simple and efficient technique of hydrogel
      mediated electropolymerization to directly pattern films of PPy (polypyrrole)
      with spatially-addressable chemistries. This technique employs a topographically
      patterned hydrogel stamp to deliver polymer precursors to the surface of
      electrode during the PPy electropolymerization. This method enables easy
      incorporation of different molecules into CP film during the polymerization.
      Herein, we aim to extend the scope of hydrogel-mediated electropolymerization to
      pattern other types of CPs and to explore the potential of bio-functionalized CP
      films for cell adhesion studies. Using this method, patterned films of two
      distinct CPs, PPy and PEDOT, were generated with a number of dopants. The
      produced films were characterized for morphology, impedance, and chemical
      composition. Patterned CP films were bio-functionalized by incorporation of a
      laminin peptide into these films. Lastly, the resultant substrates were tested
      for cell adhesion where laminin-doped CP showed a higher level of cell adhesion
      compared to PSS (polystyrene sulfonate)-doped CP films. These results together
      demonstrate the potential application of patterned films of bio-functionalized
      CPs for cellular engineering.

PMID- 29060188
TI  - Visible light-based stereolithography bioprinting of cell-adhesive gelatin
      hydrogels.
AB  - Stereolithography-based bioprinting offers advantages in resolution and rapid
      printing time, and thus has received major attention in recent years. However,
      traditional stereolithography-based bioprinting utilizes an ultraviolet light
      which may cause mutagenesis and carcinogenesis of cells. In this paper, we
      present a new visible light crosslinkable bioink that is based on cell-adhesive
      gelatin. The bioink consists of Eosin Y (EY) based photoinitiator and gelatin
      methacrylate (GelMA) pre-polymer solution. We examined the feasibility of using
      visible light from a commercial beam projector to pattern the EY-GelMA bioink. We
      measured the absorbance of bioink to characterize its sensitivity to visible
      light and performed bioprinting to test its ability to promote cell adhesion. It
      is found that the EY-GelMA bioink has an absorption peak at roughly 522 nm, and
      that it can be successfully crosslinked by visible light from the commercial
      projector. We performed the bioprinting experiments and visualized the cell
      morphology using nuclei/F-actin staining. Experimental results show that most of
      the cells attached to the EY-GelMA bioink after five days' culturing. Ultimately,
      the EY-GelMA bioink can support both visible light crosslinking and cell
      adhesion, offering great potential in bioprinting and tissue engineering.

PMID- 29060189
TI  - Manual centrifuge system: Bearing-based hand spinner made with 3-D printer.
AB  - Compact disk (CD) Microfluidic platforms are being studied for medical
      applications such as blood tests. However, its size is bulky and electricity is
      needed to realize centrifuge force. In this paper, bearing-based hand spinner is
      designed using three-dimensional printer. This spinner does not need electricity
      and keeps rotating direction unlike paperfuge while it is spinning. The
      properties of spinner vary depending on bearing type which is positioned at the
      center. The type of weighting area also affects change in RPM over time. When a
      separation experiment is implemented, separating mixture into red ink and oil and
      whole blood into red blood cell and plasma are achieved properly with ceramic
      ball bearing.

PMID- 29060190
TI  - Directed cell migration in co-cultures by topographic curvature for heterogeneous
      tissue engineering.
AB  - Placing cells in the proper position is important for tissue engineering.
      Previous works addressed this subject in the way of controlling cell migration by
      micro- or nano-patterning the substrates. However, the problem of changing
      spatial cell density freely under co-culture conditions is remaining. To solve
      this problem, in this work, we report that C2C12 spatial cell density changes by
      the patterning geometric boundary of the topographical structures. In 48 h after
      seeding cells, at the linear boundary (ridge-groove) structures, C2C12
      Groove/Ridge ratio was under 0.70 both under monoculture conditions and under co
      culture conditions. In contrast, at the combining the linear boundary and the
      round boundary (ridge-groove + hole) structures, the ratio was over 0.89 under
      both culture conditions. This our finding will provide a new device which enables
      to manipulate spatial cell density under co-culture conditions for heterogeneous
      tissue engineering.

PMID- 29060191
TI  - Development of biomimetic system for scale up of cell spheroids - building blocks
      for cell transplantation.
AB  - Artificial assembly of mature tissues in vitro is challenging from many
      viewpoints. Therefore, production of intermediate building blocks - cell
      spheroids expected to be a viable alternative. The purpose of this research is to
      develop a biomimetic system for scale up maintenance of spheroids in vitro, and
      to confirm basic performance of the device. The system consists of a 3D culture
      unit and a medium perfusion unit. The 3D culture unit is dedicated for spheroid
      culture without using scaffolds, eliminating concerns about biocompatibility of
      artificial materials. our culture vessel allows easy disassembly and tissue
      extraction, as well as the resulting tissue can be formed into an any desirable
      shape. The spheroids are cultured in a sealed environment and their life are
      sustained by hollow fiber perfusion fluidics. We confirmed by visual and by
      microscopic examination that no contamination did occur before and after spheroid
      inoculation. Moreover, we confirmed growth and fusion between cells when C2C12
      spheroids were cultured in this system.

PMID- 29060192
TI  - Enabling 3D hepatocyte spheroids for microphysiometry.
AB  - Advances in the areas of tissue engineering and microfabrication techniques have
      enabled promising in vitro platforms, known as Organs-on-Chips, with the aim of
      mimicking complex in vivo conditions for more accurate toxicology studies. To
      analyze the physiological change induced by chemicals or toxic substances
      continuously, sensors can be used in order to measure the intracellular and
      extracellular environment of single cells, cell constructs, or tissue, and
      therefore the integration of monitoring techniques into 3D tissue culture
      platforms provides an essential step for the next generation Organ-on-Chip
      platforms. However, current in vitro platforms are not capable of combining the
      culture of 3D models with monitoring techniques. To address this, a novel
      spheroid encapsulation is designed for fluidic contact between 3D models in
      microwells and Intelligent Mobile Lab for In Vitro Diagnostics (IMOLA-IVD)
      BioChip sensors while preventing spheroid fusion. In this work, spheroid
      culturing protocols were developed for optimized spheroid growth and an
      evaluation of spheroid integrity on different porous layers was performed in
      order to provide a defined spheroid encapsulation on BioChip sensors.

PMID- 29060193
TI  - Gender difference of ankle stability in the sagittal and frontal planes.
AB  - This paper offers quantification of ankle stability in relation to simulated
      haptic environments of varying stiffness. This study analyzes the stability
      trends of male and female subjects independently over a wide range of simulated
      environments after subjects were exposed to vigorous position perturbation. Ankle
      stability was quantified for both degrees-of-freedom of the ankle in the sagittal
      and frontal planes. Subjects' stability consistently decreased when exposed to
      environments of negative simulated stiffness. In the frontal plane, male and
      female subjects exhibited nearly identical stability levels. In the sagittal
      plane, however, male subjects demonstrated marginally more stability than female
      subjects in environments with negative stiffness. Results of this study are
      beneficial to understanding situations in which the ankle is likely to lose
      stability, potentially resulting in injury.

PMID- 29060194
TI  - Effects of counteracting external valgus moment on lateral tibial cartilage
      contact conditions and tibial rotation.
AB  - Knee osteoarthritis that prevalently occurs at the medial compartment is a
      progressive chronic disorder affecting the articular cartilage of the knee joint,
      and lead to loss of joint functionality. Valgus braces have been used as a
      treatment procedure to unload the medial compartment for patients with medial
      osteoarthritis. Valgus braces through the application of counteracting external
      valgus moment shift the load from medial compartment towards the lateral
      compartment. Previous biomechanical studies focused only on the changes in varus
      moments before and after wearing the brace. The objective of this study was to
      investigate the influence of opposing external valgus moment applied by knee
      braces on the lateral tibial cartilage contact conditions using a 3D finite
      element model of the knee joint. Finite element simulations were performed on the
      knee joint model without and with the application of opposing valgus moment to
      mimic the unbraced and braced conditions. Lateral tibial cartilage contact
      pressures and contact area, and tibial rotation (varus-valgus and internal
      external) were estimated for the complete walking gait cycle. The opposing valgus
      moment increased the maximum contact pressure and contact area on the lateral
      tibial cartilage compared to the normal gait moment. A peak contact pressure of
      8.2 MPa and maximum cartilage loaded area of 28% (loaded cartilage nodes) on the
      lateral cartilage with the application of external valgus moment were induced at
      50% of the gait cycle. The results show that the use of opposing valgus moment
      may significantly increase the maximum contact pressures and contact area on the
      lateral tibial cartilage and increases the risk of articular cartilage damage on
      the lateral compartment.

PMID- 29060195
TI  - Assessment of 3D morphological characteristics of the shoulder bones using
      statistical shape modeling: Prospective application to handedness.
AB  - In this study we have described the use of statistical shape modeling (SSM)
      technique in evaluating the morphological variation of shoulder bones from a
      South African population. The anatomical landmark selections were carried out,
      followed by the registration of the meshes which were validated before
      establishing the dense correspondence. The SSMs were built and average shape
      comparison from each side for each bone were made in order to evaluate
      handedness. In general, there was no error found around the gleno-humeral region
      which may suggest that the usage of contralateral healthy shoulder could serve as
      an informed decision making tool for surgery and prosthesis design.

PMID- 29060196
TI  - The use of shear thickening polymer as a hip protecter.
AB  - External hip protectors are used by the elderly in preventing hip fracture due to
      sideway falls. There are some commercial hip protectors which has both energy
      absorbing and energy shunting properties. In this study, a novel hip protector
      using shear thickening polymer (STP) is studied. The purpose of this work is to
      determine the optimal thickness of STP needed for maximum force attenuation. A
      mechanical test rig to simulate a person falling with sufficient impact energy to
      fracture the greater trochanter if unprotected was used together with biofidelic
      femur model which simulates the layer of flesh with skin. 8mm of STP together
      with 5mm foam gives the best force attenuation. When comparing the overall
      thickness with commercial hip protectors, STP hip protectors tested have much
      less thickness. Reduced thickness increases the compliance and comfort of STP hip
      protectors.

PMID- 29060197
TI  - Risk estimation for intervertebral disc pressure through musculoskeletal joint
      reaction force simulation.
AB  - This research proposes a novel method that evaluates joint reaction forces by
      motion analysis using a musculoskeletal model. While general muscle tension
      estimations minimize the sum of the muscle tensions, the proposed method utilizes
      the joint reaction forces themselves in the objective function of the
      optimization problem in addition to conventional method. This method can estimate
      a pattern of the muscle tensions that maximizes or minimizes a specific joint
      force. As a typical outcome, the proposed method allows evaluating intervertebral
      disc compressive force caused by co-contraction of muscles while avoiding risk
      underestimation. We analyzed the actual lifting motion as an example and
      confirmed that the method can estimate the muscle tension distribution under
      different tension conditions.

PMID- 29060198
TI  - Subject-specific shoulder muscle attachment region prediction using statistical
      shape models: A validity study.
AB  - Subject-specific musculoskeletal models can predict accurate joint and muscle
      biomechanics thereby helping clinicians and surgeons. Current modeling strategies
      do not incorporate accurate subject-specific muscle parameters. This study
      reports a statistical shape model (SSM) based method to predict subject-specific
      muscle attachment regions on shoulder bones and illustrates the concurrent
      validity of the predictions. Augmented SSMs of scapula and humerus bones were
      built using bone meshes and five muscle attachment (origin/insertion) regions
      which play important role in the shoulder motion and function. Muscle attachments
      included Subscapularis, Supraspinatus, Infraspinatus, Teres Major and Teres Minor
      on both the bones. The regions were represented by subset of vertices on the bone
      meshes and were tracked using vertex identifiers. Subject-specific muscle
      attachment regions were predicted using external set of bones not used in
      building the SSMs. Validity of predictions was determined by visual inspection
      and also by using four similarity measures between predicted and manually
      segmented regions. Excellent concurrent validity was found indicating the higher
      accuracy of predictions. This method can be effectively employed in modeling
      pipelines or in automatic segmentation of medical images. Further validations are
      warranted on all the muscles of the shoulder complex.

PMID- 29060199
TI  - Neural decoding of attentional selection in multi-speaker environments without
      access to separated sources.
AB  - People who suffer from hearing impairments can find it difficult to follow a
      conversation in a multi-speaker environment. Modern hearing aids can suppress
      background noise; however, there is little that can be done to help a user attend
      to a single conversation without knowing which speaker is being attended to.
      Cognitively controlled hearing aids that use auditory attention decoding (AAD)
      methods are the next step in offering help. A number of challenges exist,
      including the lack of access to the clean sound sources in the environment with
      which to compare with the neural signals. We propose a novel framework that
      combines single-channel speech separation algorithms with AAD. We present an end
      to-end system that 1) receives a single audio channel containing a mixture of
      speakers that is heard by a listener along with the listener's neural signals, 2)
      automatically separates the individual speakers in the mixture, 3) determines the
      attended speaker, and 4) amplifies the attended speaker's voice to assist the
      listener. Using invasive electrophysiology recordings, our system is able to
      decode the attention of a subject and detect switches in attention using only the
      mixed audio. We also identified the regions of the auditory cortex that
      contribute to AAD. Our quality assessment of the modified audio demonstrates a
      significant improvement in both subjective and objective speech quality measures.
      Our novel framework for AAD bridges the gap between the most recent advancements
      in speech processing technologies and speech prosthesis research and moves us
      closer to the development of cognitively controlled hearing aids.

PMID- 29060200
TI  - TrueNorth-enabled real-time classification of EEG data for brain-computer
      interfacing.
AB  - Brain-computer interfaces are commonly proposed to assist individuals with locked
      in syndrome to interact with the world around them. In this paper, we present a
      pipeline to move from recorded brain signals to real-time classification on a low
      power platform, such as IBM's TrueNorth Neurosynaptic System. Our results on a
      EEG-based hand squeeze task show that using a convolutional neural network and a
      time preserving signal representation strategy provides a good balance between
      high accuracy and feasibility in a real-time application. This pathway can be
      adapted to the management of a variety of conditions, including spinal cord
      injury, epilepsy and Parkinson's disease.

PMID- 29060201
TI  - An eighty-target high-speed Chinese BCI speller.
AB  - A high-speed Chinese Brain-computer interface (BCI) speller was designed and
      implemented in this paper. A visual stimulation method called the motion
      checkerboard stimulation was used to elicit steady-state visual evoked potentials
      (SSMVEP). With a 10 * 8 high-density matrix interface, phonetic symbols or
      Chinese characters (sinograms) were presented for selection, and only two
      selections per character were required. According to experiment results, the ITR
      of the eighty-target motion checkerboard paradigm achieved 99.1 bits/min, the
      average accuracy of sinogram spelling system scored above 94.1% and the speed was
      up to one sinogram per 13.6 s. These results suggest that the proposed Chinese
      speller can input vast number of characters with higher speed and less
      operations, providing a high practicability communication method for people with
      motor disabilities.

PMID- 29060202
TI  - Cortical oscillatory dynamics of tactile selective sensation - for a novel type
      of somatosensory Brain-computer Interface.
AB  - In this study, cortical oscillatory dynamics with respect to tactile selective
      sensation tasks were investigated. Subjects were required to perform three
      tactile attention tasks, prompted by cues presented in random order and while
      both wrists were simultaneously stimulated: 1) selective sensation of the left
      hand (SS-L), 2) selective sensation of the right hand (SS-R), 3) bilateral
      selective sensation (SS-B). Even-related (de)synchronization (ERD/ERS) analysis
      revealed a clear contralateral activation of somatosensory cortex during the SS-L
      and SS-R tasks, and a bilateral activation during SS-B tasks. Additionally, we
      found a clear ERS in occipital region of the brain during all the SS tasks.
      Diverse activation pattern among SS-L, SS-R and SS-B offers novel brain signals
      for somatosensory Brain-computer Interfaces.

PMID- 29060203
TI  - Dynamic tracking of non-stationarity in human ECoG activity.
AB  - Modeling brain network dynamics is essential in understanding neural mechanisms
      and developing neurotechnologies such as closed-loop stimulation therapies for a
      wide range of neurological disorders. Brain network activity could have non
      stationary and time-variant dynamics, especially when the subject's brain is
      monitored for a long period, e.g., using the electrocorticogram (ECoG). This non
      stationarity makes the modeling of dynamics challenging. In our prior work, we
      developed a framework to identify time-invariant linear state-space models (SSMs)
      to describe both stationary spontaneous neural population dynamics and input
      output (IO) neural dynamics in response to electrical stimulation. Here, we
      develop an adaptive identification algorithm that estimates time-variant SSMs to
      track possible non-stationarity in brain network dynamics. We apply the adaptive
      algorithm to track high-density human ECoG dynamics in three subjects over a long
      time-period. We find that the adaptive identification algorithm can estimate time
      variant SSMs that significantly outperform time-invariant SSMs in all subjects.
      Our results demonstrate that non-stationary dynamics exist in high-dimensional
      human ECoG signals over long time-periods, and that the proposed adaptive SSM
      identification algorithm can successfully track these non-stationarities. These
      results have important implications for more accurate estimation of neural
      biomarkers for different brain states and for adaptive closed-loop stimulation
      therapy across a wide range of neurological disorders.

PMID- 29060204
TI  - Movement-related brain oscillations vary with lesion location in severely
      paralyzed chronic stroke patients.
AB  - In the past few years, innovative upper-limb rehabilitation methods have been
      proposed for chronic stroke patients. These methods aim at functional motor
      rehabilitation using Brain-machine interfaces to constitute an alternate pathway
      from the brain to the muscles. Even in patients with absence of residual finger
      movements, recovery could be achieved. The extent to which these interventions
      are affected by individual lesion topology is yet to be understood. In this study
      EEG was measured in 30 chronic stroke patients during movement attempts of the
      paretic arm. We show that the magnitude of the event-related desynchronization
      was smaller in patients presenting lesions with involvement of the motor cortex.
      This could have important implications on the design of new rehabilitation
      schemes for these patients, which might benefit from carefully tailored
      interventions.

PMID- 29060205
TI  - Prediction of adenocarcinoma development using game theory.
AB  - Recent research shows that gene expression changes appear to correlate well with
      the progression of many types of cancers. Using changes in gene expression as a
      basis, this paper proposes a data-driven 2-player game-theoretic model to predict
      the risk of adenocarcinoma based on Nash equilibrium. A key innovation in this
      work is the pay-off function which is a weighted composite of the expression of a
      cohort of tumor-suppressor genes (as one player) and an analogous cohort of
      oncogenes (as the other player). Another novelty of the model is its ability to
      predict the risk that a healthy sample will develop adenocarcinoma, if its
      associated gene expression is comparable to that of early-stage tumor samples.
      The model is validated using two of the largest publicly available adenocarcinoma
      datasets. The results show that i) the model is able to distinguish between
      healthy and cancerous samples with an accuracy of 93%, and ii) 95% of the healthy
      samples said to be at risk had gene expressions comparable to those of samples
      with stage I or stage II tumors, thereby predicting the imminent onset of
      adenocarcinoma.

PMID- 29060206
TI  - Learning from different perspectives: Robust cardiac arrest prediction via
      temporal transfer learning.
AB  - Predicting and preventing cardiac arrest is one of the biggest challenges of
      contemporary cardiology, as a patients survival depends on the effectiveness of
      the emergency response teams. While black-box models have shown to have better
      predictive accuracies for cardiac risk stratification, early warning scoring
      systems are more prominent in the hospital setting due to their ease of
      implementation and interpretability. We propose a temporal transfer learning
      approach to utilize information from adjacent time points to yield an early
      cardiac arrest prediction model that is robust in predictive accuracies as well
      as maintains the interpretability of the model coefficients. Our model estimates
      the logistic regression coefficients simultaneously for various time points to
      share knowledge from different observation windows. This framework can overcome
      small sample size issues, and result in robust estimation of the model
      coefficients. We find that our model consistently outperforms a logistic
      regression model fit only on vital sign data from a single time slice for 763
      intensive care unit patients. Moreover, we find that the estimated coefficients
      from our model captures temporal trends in the data.

PMID- 29060207
TI  - Predictive modeling for corrective maintenance of imaging devices from machine
      logs.
AB  - In the cost sensitive healthcare industry, an unplanned downtime of diagnostic
      and therapy imaging devices can be a burden on the financials of both the
      hospitals as well as the original equipment manufacturers (OEMs). In the current
      era of connectivity, it is easier to get these devices connected to a standard
      monitoring station. Once the system is connected, OEMs can monitor the health of
      these devices remotely and take corrective actions by providing preventive
      maintenance thereby avoiding major unplanned downtime. In this article, we
      present an overall methodology of predicting failure of these devices well before
      customer experiences it. We use data-driven approach based on machine learning to
      predict failures in turn resulting in reduced machine downtime, improved customer
      satisfaction and cost savings for the OEMs. One of the use-case of predicting
      component failure of PHILIPS iXR system is explained in this article.

PMID- 29060208
TI  - Data-driven strategies for robust forecast of continuous glucose monitoring time
      series.
AB  - Over the past decade, continuous glucose monitoring (CGM) has proven to be a very
      resourceful tool for diabetes management. To date, CGM devices are employed for
      both retrospective and online applications. Their use allows to better describe
      the patients' pathology as well as to achieve a better control of patients' level
      of glycemia. The analysis of CGM sensor data makes possible to observe a wide
      range of metrics, such as the glycemic variability during the day or the amount
      of time spent below or above certain glycemic thresholds. However, due to the
      high variability of the glycemic signals among sensors and individuals, CGM data
      analysis is a non-trivial task. Standard signal filtering solutions fall short
      when an appropriate model personalization is not applied. State-of-the-art data
      driven strategies for online CGM forecasting rely upon the use of recursive
      filters. Each time a new sample is collected, such models need to adjust their
      parameters in order to predict the next glycemic level. In this paper we aim at
      demonstrating that the problem of online CGM forecasting can be successfully
      tackled by personalized machine learning models, that do not need to recursively
      update their parameters.

PMID- 29060209
TI  - Prediction of temperature induced office worker's performance during typing task
      using EEG.
AB  - Understanding how indoor environment affects office worker's performance and
      developing methods to predict human performance in changing indoor environment
      have become highly important research topic bearing significant economic and
      sociological impact. While past research groups have attempted to find predictors
      for performance they do not provide satisfactory predictions. We conduct in this
      paper a study to predict human performance by developing a regression model using
      neurophysiological signals collected from electroencephalogram (EEG), during
      simulated office-work tasks under different indoor room temperatures (22 degrees
      C and 30 degrees C). We found that using brain power spectral densities (PSD)
      from EEG as predictors provides the higher R2 than predictors using skin
      temperature or heart rate by approximately over 3 folds. Finally, we showed that
      the predictor using EEG is more robust than regression models using skin
      temperature and heart rate. Our work shows the potential of using brain signals
      to accurately predict human office work performance.

PMID- 29060210
TI  - Consensus motifs as adaptive and efficient predictors for acute hypotensive
      episodes.
AB  - Acute hypotensive episodes (AHE) are characterized by continuously low blood
      pressure for prolonged time, and could be potentially fatal. We present a novel
      AHE detection system, by first quantizing the blood pressure data into clinically
      accepted severity ranges and then identifying most frequently occurring blood
      pressure pattern among these which we call consensus motifs. We apply machine
      learning techniques (support vector machine) on these consensus motifs. The
      results show that the use of consensus motifs instead of raw time series data
      extends the predictability by 45 minutes beyond the 2 hours that is possible
      using only the raw data, yielding a significant improvement without compromising
      the clinical accuracy. The system has been implemented as part of a new framework
      called RASPRO (Rapid Summarization for Effective Prognosis) that we have
      developed for Wireless Remote Health Monitoring.

PMID- 29060211
TI  - Model-based estimation of radial artery blood pressure from recordings of the
      Nexfin monitor.
AB  - We propose a model-based reconstruction technique to estimate radial artery blood
      pressure from measurements obtained by the Nexfin noninvasive blood pressure
      monitor. The Nexfin monitor provides brachial artery pressure estimates by
      transforming a pressure measured at the finger. The estimated brachial pressure
      differs significantly from the radial artery pressure commonly measured in
      intensive care applications. Our reconstruction method is based on a transmission
      line model of the arterial network and transforms brachial to radial pressure
      estimates. Applying the method to 22 records from six patients reduced mean pulse
      pressure differences between reconstructed and measured radial artery pressures
      from -17.9 (s.d. 12.1) mmHg to 1.8 (12.0) mmHg. Mean systolic and diastolic
      pressure differences changed from -18.7 (10.5) and -0.7 (6.2) to -0.8 (10.5) and 
      2.6 (6.9) mmHg, respectively. Our method can be applied to more general problems
      of estimating pressure waveforms downstream from an upstream measurement
      location.

PMID- 29060212
TI  - A simple method for reconstruction of continuous brachial artery pressure from
      continuous digital artery pressure in humans.
AB  - This paper presents a practical approach to reconstruct brachial artery pressure
      (BAP) distally from digital artery pressure (DAP). We hypothesize that continuous
      BAP can simply be approximated by sum of two halves of the continuous DAP shifted
      by the time delay. In order to test it, we enrolled 30 healthy volunteers for two
      experiments. We firstly showed that the pressure wave in the digital artery can
      be considered twice as much as the forward/backward wave in the finger. A
      simplified individualized transfer function was then derived so as to estimate
      BAP from DAP. Finally, by comparing with a reference BAP, we found that the
      proposed method can correct the DAP. The errors of the proposed method in
      estimating systolic and diastolic pressures are 2.82+/-3.58 and -2.32+/-4.06
      mmHg, respectively. These results agree with the standard of Association for the
      Advancement of Medical Instrumentation (AAMI). Our method is therefore promising
      in estimating continuous proximal blood pressure from peripheral blood pressure
      in practice.

PMID- 29060213
TI  - Measurement of carotid blood pressure and local pulse wave velocity changes
      during cuff induced hyperemia.
AB  - We present a prototype design of dual element photoplethysmograph (PPG) probe
      along with associated measurement system for carotid local pulse wave velocity
      (PWV) evaluation in a non-invasive and continuous manner. The PPG probe consists
      of two identical sensing modules placed 23 mm apart. Simultaneously measured
      blood pulse waveforms from these arterial sites were processed and the pulse
      transit time delay was resolved using the developed application-specific
      software. The ability of developed PPG probe and associated measurement system to
      detect acute changes in carotid local PWV due to blood pressure (BP) variations
      was experimentally validated by an in-vivo study. Intra-subject carotid BP
      elevation was achieved by an upper arm cuff based occlusion, which offered a
      controlled way of local PWV escalation. The elevated carotid BP values were also
      recorded by a calibrated pressure tonometer prior to the study, and was used as a
      reference. A significant increment (1.0 - 2.6 m/s) in local PWV was observed and
      was proportional to the BP increment induced by the occlusive reactive hyperemia.
      Study results demonstrated the feasibility of real-time signal acquisition and
      reliable local PWV evaluation under normal and elevated BP conditions using the
      developed measurement system.

PMID- 29060214
TI  - Analysis of a GMR-based plethysmograph transducer and its utility for real-time
      Blood Pressure measurement.
AB  - The paper presents study and analysis of a Giant Magneto Resistance (GMR)-based
      magneto plethysmograph and illustrates its efficacy as a tool for real-time cuff
      less measurement of Blood Pressure (BP). The proposed scheme employs two GMR
      sensors and associated biasing and signal conditioning in its architecture. The
      delay between output of the GMR sensors is used to estimate the BP. The
      methodology, circuits and signal processing stages used are described in the
      paper. A prototype of the GMR-sensing solution is developed and tested.
      Initially, tests are carried out to determine the quality and characteristics of
      the plethysmographs produced by developed sensor unit, in different conditions
      such as various body positions, bias current etc. Good quality bio-signals were
      obtained during the above tests. Then, the experiments were conducted on 29
      volunteers to find the feasibility of developed scheme as a BP monitor. The
      results obtained show that the performance of developed BP monitor is within
      acceptable limits.

PMID- 29060215
TI  - Regression analysis and transfer function in estimating the parameters of central
      pulse waves from brachial pulse wave.
AB  - This study mainly analyzed the parameters such as ascending branch slope
      (A_slope), dicrotic notch height (Hn), diastolic area (Ad) and systolic area (As)
      diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure
      (PP), subendocardial viability ratio (SEVR), waveform parameter (k), stroke
      volume (SV), cardiac output (CO) and peripheral resistance (RS) of central pulse
      wave invasively and non-invasively measured. These parameters extracted from the
      central pulse wave invasively measured were compared with the parameters measured
      from the brachial pulse waves by a regression model and a transfer function
      model. The accuracy of the parameters which were estimated by the regression
      model and the transfer function model was compared too. Our findings showed that
      in addition to the k value, the above parameters of the central pulse wave and
      the brachial pulse wave invasively measured had positive correlation. Both the
      regression model parameters including A_slope, DBP, SEVR and the transfer
      function model parameters had good consistency with the parameters invasively
      measured, and they had the same effect of consistency. The regression equations
      of the three parameters were expressed by Y'=a+bx. The SBP, PP, SV, CO of central
      pulse wave could be calculated through the regression model, but their accuracies
      were worse than that of transfer function model.

PMID- 29060216
TI  - Novel blood pressure estimation method using single photoplethysmography feature.
AB  - Continuous blood pressure (BP) monitoring has a significant meaning to the
      prevention and early diagnosis of cardiovascular disease. However, existing
      continuous BP monitoring approaches, especially cuff-less BP monitoring
      approaches, are all contraptions which complex and huge computation required. For
      example, for the most sophisticated cuff-less BP monitoring method using pulse
      transit time (PTT), the simultaneous record of photoplethysmography (PPG) signal
      and electrocardiography (ECG) are required, and various measurement of
      characteristic points are needed. These issues hindered widely application of
      cuff less BP measurement in the wearable devices. In this study, a novel BP
      estimation method using single PPG signal feature was proposed and its
      performance in BP estimation was also tested. The results showed that the new
      approach proposed in this study has a mean error -0.91 +/- 3.84 mmHg for SBP
      estimation and -0.36 +/- 3.36 mmHg for DBP estimation respectively. This approach
      performed better than the traditional PTT based BP estimation, which mean error
      for SBP estimation was -0.31 +/- 4.78 mmHg, and for DBP estimation was -0.18 +/-
      4.32 mmHg. Further investigation revealed that this new BP estimation approach
      only required measurement of one characteristic point, reducing much computation
      when implementing. These results demonstrated that this new approach might be
      more suitable implemented in the wearable BP monitoring devices.

PMID- 29060217
TI  - Chronic multi-region recording from the rat hippocampus in vivo with a flexible
      Parylene-based multi-electrode array.
AB  - Neural activities of free-moving animals provide valuable insights into behavior,
      memory formation and cognitive function of the hippocampus. Unitary activities
      simultaneously recorded from multiple sub-regions of the hippocampus enable
      detailed study of hippocampal neural circuits, but require high fidelity
      recordings with high temporal and spatial resolution. In this work, we explored
      the possibility of using Parylene-C as the structural material for a penetrating,
      multi-electrode array designed to record from multiple sub-region of the rat
      hippocampus. A 64-channel Parylene-based flexible electrode array was designed
      and fabricated. The layout of the electrode array was arranged to conform to the
      shape of cell body layers of the rat hippocampus. An insertion technique of
      temporarily reduce the effective length of the probe with polyethylene glycol
      (PEG) was developed and tested in vivo. The multi-electrode array was implanted
      into a rat hippocampus for chronic experimentation and unitary activities were
      collected both during the implantation and after recovery while the animal ran
      freely in an open field. Unitary activities with an average signal to noise
      ratios (SNR) of 3 to 4 were recorded with the Parylene probe over the period of
      one month after implantation.

PMID- 29060218
TI  - Development and characterization of a fully flexible stimulation system based on
      embedded liquid metal channels.
AB  - Neuronal stimulation systems design is highly impacted by the overall resolution
      and adaptability of the device to the targeted application and area to stimulate.
      In this study is proposed a novel design for neural micro-stimulation electrode
      presenting high resolution and adaptability to any targeted area via a high
      flexibility. The use of liquid metal micro-channels encapsulated into a polymer
      allowed micro-stimulation pads at the tip of the channels. It presented a high
      degree of patternability to match different possible applications, as well as
      flexibility and interesting mechanic properties to make it insertable and
      adaptable in soft tissues. The design, fabrication process, and study of the
      electrical and mechanical behavior and stability of the device are discussed.
      Conductive U-shaped micro-channels down to a total diameter of 110 MUm could be
      produced.

PMID- 29060219
TI  - Using impedance to track fracture healing rates in mice in vivo: A pilot study.
AB  - Fracture injuries are highly prevalent worldwide, with treatment of problematic
      fractures causing a significant burden on the U.S. healthcare system. Physicians
      typically monitor fracture healing by conducting physical examinations and taking
      radiographic images. However, nonunions currently take over 6 months to be
      diagnosed because these techniques are not sensitive enough to adequately assess
      fracture union. In this study, we display the utility of impedance spectroscopy
      to track different healing rates in a pilot study of an in vivo mouse tibia
      fracture model. We have developed small (56 MUm) sensors and implanted them in an
      externally-stabilized fracture for twice-weekly measurement. We found that
      impedance magnitude increases steadily over time in healing mice but stalls in
      non-healing mice, and phase angle displays frequency-dependent behavior that also
      reflects the extent of healing at the fracture site. Our results demonstrate that
      impedance can track differences in healing rates early on, highlighting the
      potential of this technique as a method for early detection of fracture nonunion.

PMID- 29060220
TI  - Effect of temperature variation on remote pressure readout in wirelessly powered
      intracranial pressure monitoring system.
AB  - An implantable pressure monitoring system is a compelling approach to home
      monitoring of intracranial pressure in the long term. In our approach, an on-body
      unit powers a cranially concealed system where a piezoresistive element senses
      the pressure. A data transmission unit built in the same platform emits a signal
      at a pressure dependent frequency through a miniature far field antenna. In this
      work, we focus on assessing the impact of variable temperature on the pressure
      readout at an off-body unit through in-vitro experiments.

PMID- 29060221
TI  - Implantable bladder volume sensor based on resistor ladder network composed of
      conductive hydrogel composite.
AB  - An accurate bladder volume monitoring system is a critical component in diagnosis
      and treatment of urological disorders. Here, we report an implantable bladder
      volume sensor with a multi-level resistor ladder which estimates the bladder
      volume through discrete resistance values. Discretization allows the sensor
      output to be resilient to the long-term drift, hysteresis, and degradation of the
      sensor materials. Our sensor is composed of biocompatible polypyrrole/agarose
      hydrogel composite. Because Young's modulus of this composite is comparable to
      that of the bladder wall, the effect of mechanical loading of the sensor on the
      bladder movement is minimized which allows more accurate volume monitoring. We
      also demonstrate the patterning and molding capability of this material by
      fabrication various structures. Lastly, we successfully demonstrate the
      functionality of the multi-level resistor ladder sensor as a bladder volume
      sensor by attaching the sensor on the pig's bladder and observing the impedance
      change of the sensor.

PMID- 29060222
TI  - Integrating coupled magnetoelastic sensors onto a flexible hernia mesh for high
      dynamic range strain measurements.
AB  - Despite better performance over primary repairs, tension-free ventral hernia
      repairs with mesh still suffer from a high recurrence rate. High stress gradients
      in the mesh are thought to contribute to hernia recurrence. We propose a
      postoperative monitoring system based on a coupled pair of magnetoelastic strain
      sensors to enable patients and physicians to non-invasively measure and track the
      strain distribution across the hernia mesh. Our design combines an encased
      resonator with a spring-loaded transducer to achieve high signal amplitude with a
      wide dynamic range. We also demonstrate a fabrication protocol to integrate the
      resonant strain sensors with a commercial polypropylene mesh. The packaged sensor
      is capable of detecting up to 37.5 millistrain, an order of magnitude greater
      than previously demonstrated.

PMID- 29060223
TI  - Abnormality detection of mammograms by discriminative dictionary learning on
      DSIFT descriptors.
AB  - Detection and classification of breast lesions using mammographic images are one
      of the most difficult studies in medical image processing. A number of learning
      and non-learning methods have been proposed for detecting and classifying these
      lesions. However, the accuracy of the detection/classification still needs
      improvement. In this paper we propose a powerful classification method based on
      sparse learning to diagnose breast cancer in mammograms. For this purpose, a
      supervised discriminative dictionary learning approach is applied on dense scale
      invariant feature transform (DSIFT) features. A linear classifier is also
      simultaneously learned with the dictionary which can effectively classify the
      sparse representations. Our experimental results show the superior performance of
      our method compared to existing approaches.

PMID- 29060224
TI  - Exudate detection for diabetic retinopathy with convolutional neural networks.
AB  - Exudate detection is an essential task for computer-aid diagnosis of diabetic
      retinopathy (DR), so as to monitor the progress of DR. In this paper, deep
      convolutional neural network (CNN) is adopted to achieve pixel-wise exudate
      identification. The CNN model is first trained with expert labeled exudates image
      patches and then saved as off-line classifier. In order to achieve pixel-level
      accuracy meanwhile reduce computational time, potential exudate candidate points
      are first extracted with morphological ultimate opening algorithm. Then the local
      region (64 * 64) surrounding the candidate points are forwarded to the trained
      CNN model for classification/identification. A pixel-wise accuracy of 91.92%,
      sensitivity of 88.85% and specificity of 96% is achieved with the proposed CNN
      architecture on the test database.

PMID- 29060225
TI  - CEUS-based classification of liver tumors with deep canonical correlation
      analysis and multi-kernel learning.
AB  - The contrast-enhanced ultrasound (CEUS) has been a widely accepted imaging
      modality for diagnosis of liver cancers. In clinical practice, several typical
      images selected from enhancement patterns of the arterial, portal venous and late
      phases can provide reliable information basis for diagnosis. In this work, we
      propose to develop a CEUS-based computer-aided diagnosis (CAD) for liver cancers
      with only three typical CEUS images selected from three phases, which simulates
      the clinical diagnosis mode of radiologists. In the proposed CAD, the deep
      canonical correlation analysis (DCCA) is first performed on three CEUS pairs
      between arterial and portal venous phases, arterial and late phases,
      respectively, due to the effectiveness of multi-view fusion of DCCA. The
      generated six-view features are then fed to a multiple kernel learning (MKL)
      classifier to further promote the predictive diagnosis result. The experimental
      results indicate that the proposed DCCA-MKL algorithm achieves best performance
      for discriminating benign liver tumors from malignant liver cancers.

PMID- 29060226
TI  - A multi-view deep convolutional neural networks for lung nodule segmentation.
AB  - We present a multi-view convolutional neural networks (MV-CNN) for lung nodule
      segmentation. The MV-CNN specialized in capturing a diverse set of nodule
      sensitive features from axial, coronal and sagittal views in CT images
      simultaneously. The proposed network architecture consists of three CNN branches,
      where each branch includes seven stacked layers and takes multi-scale nodule
      patches as input. The three CNN branches are then integrated with a fully
      connected layer to predict whether the patch center voxel belongs to the nodule.
      The proposed method has been evaluated on 893 nodules from the public LIDC-IDRI
      dataset, where ground-truth annotations and CT imaging data were provided. We
      showed that MV-CNN demonstrated encouraging performance for segmenting various
      type of nodules including juxta-pleural, cavitary, and non-solid nodules,
      achieving an average dice similarity coefficient (DSC) of 77.67% and average
      surface distance (ASD) of 0.24, outperforming conventional image segmentation
      approaches.

PMID- 29060227
TI  - Surgical-tools detection based on Convolutional Neural Network in laparoscopic
      robot-assisted surgery.
AB  - Laparoscopic surgery, a type of minimally invasive surgery, is used in a variety
      of clinical surgeries because it has a faster recovery rate and causes less pain.
      However, in general, the robotic system used in laparoscopic surgery can cause
      damage to the surgical instruments, organs, or tissues during surgery due to a
      narrow field of view and operating space, and insufficient tactile feedback. This
      study proposes real-time models for the detection of surgical instruments during
      laparoscopic surgery by using a CNN(Convolutional Neural Network). A dataset
      included information of the 7 surgical tools is used for learning CNN. To track
      surgical instruments in real time, unified architecture of YOLO apply to the
      models. So as to evaluate performance of the suggested models, degree of recall
      and precision is calculated and compared. Finally, we achieve 72.26% mean average
      precision over our dataset.

PMID- 29060228
TI  - Deep learning-based Diabetic Retinopathy assessment on embedded system.
AB  - Diabetic Retinopathy (DR) is a disease which affect the vision ability. The
      observation by an ophthalmologist usually conducted by analyzing the retinal
      images of the patient which are marked by some DR features. However some
      misdiagnosis are usually found due to human error. Here, a deep learning-based
      low-cost embedded system is established to assist the doctor for grading the
      severity of the DR from the retinal images. A compact deep learning algorithm
      named Deep-DR-Net which fits on a small embedded board is afterwards proposed for
      such purposes. In the heart of Deep-DR-Net, a cascaded encoder-classifier network
      is arranged using residual style for ensuring the small model size. The usage of
      different types of convolutional layers subsequently guarantees the features
      richness of the network for differentiating the grade of the DR. Experimental
      results show the capability of the proposed system for detecting the existence as
      well as grading the severity of the DR symptomps.

PMID- 29060229
TI  - Development of methods for sleep disordered breathing to identify phenotypes.
AB  - Sleep disordered breathing a very common disorder with prevalence rates of up to
      49% in large epidemiological studies on subjects older than 40 years. A recent
      study showed that applying CPAP treatment to patients with sleep disordered
      breathing recruited by their number of apnea and hypopnea events alone, does
      improve sleepiness but does not improve overall cardiovascular mortality. Based
      on older large studies however it is knownthat sleep disordered breathing is a
      cardiovascular risk and that treatment lowers mortality and morbidity. These
      results appear to be contradictory. However, they might be explained if patient
      population investigated are carefully reviewed further, and if sleep apnea
      severity metrics are reconsidered. According to this, it appears that studies
      speak of different populations. Whereas epidemiological studies use sampled
      subjects willing to participate, earlier studies used patients contacting a sleep
      center with complaints and symptoms. In this paper two studies are presented with
      an assessment of anatomical metrics for upper airway morphology in order to
      derive parameters for better prediction. Different phenotypes can explain why
      some people benefit from treatment and others do not benefit equally. Therefore
      more than just counting apnea and hypopnea events is needed in order to identify
      patients at risk and patients who have a lower risk when treated. This will
      require large data set evaluations with hard outcome data.

PMID- 29060230
TI  - Remote gaze tracking system for 3D environments.
AB  - Eye tracking systems are typically divided into two categories: remote and
      mobile. Remote systems, where the eye tracker is located near the object being
      viewed by the subject, have the advantage of being less intrusive, but are
      typically used for tracking gaze points on fixed two dimensional (2D) computer
      screens. Mobile systems such as eye tracking glasses, where the eye tracker are
      attached to the subject, are more intrusive, but are better suited for cases
      where subjects are viewing objects in the three dimensional (3D) environment. In
      this paper, we describe how remote gaze tracking systems developed for 2D
      computer screens can be used to track gaze points in a 3D environment. The system
      is non-intrusive. It compensates for small head movements by the user, so that
      the head need not be stabilized by a chin rest or bite bar. The system maps the
      3D gaze points of the user onto 2D images from a scene camera and is also located
      remotely from the subject. Measurement results from this system indicate that it
      is able to estimate gaze points in the scene camera to within one degree over a
      wide range of head positions.

PMID- 29060231
TI  - Estimation of blood pressure from non-invasive data.
AB  - Blood pressure (BP) is one of the most important physiological parameter that can
      provide crucial information for health care. The widely used cuff based
      technology is not very convenient or comfortable as it occludes the blood flow in
      the arteries during the time of measurement. In past, Phonocardiogram (PCG),
      Electrocardiogram (ECG) and Photoplethysmogram (PPG) signals have been used to
      predict the BP values. In this paper, we propose to estimate the blood pressure
      from PPG using Multi Task Gaussian Processes (MTGPs) and compare with Artificial
      Neural networks (ANNs). Both MTGPs and ANNs are evaluated on the clinical data
      obtained from MIMIC Database. The performance of the proposed method is found to
      be comparable or better than the existing methods of computing BP from non
      invasive data.

PMID- 29060232
TI  - Assessment of instantaneous cardiovascular dynamics from video plethysmography.
AB  - Although there is growing interest in estimating cardiovascular information using
      contactless video plethysmography (VP), an in-depth validation of time-varying,
      nonlinear dynamics of the related pulse rate variability is still missing. In
      this study we estimate the heartbeat through VP and standard ECG, and employ
      inhomogeneous point-process nonlinear models to assess instantaneous heart rate
      variability measures defined in the time, frequency, and bispectral domains.
      Experimental data were gathered from 60 young healthy subjects (age: 24+/-3
      years) undergoing postural changes (rest-to-stand maneuver). Video recordings are
      processed using our recently proposed method based on zero-phase component
      analysis. Results show that, at a group level, there is an overall agreement
      between linear and nonlinear indices computed from ECG and VP during resting
      state conditions. However, significant differences are found, especially in the
      bispectral domain, when considering data gathered while standing. Although
      significant differences exist between cardiovascular estimates from VP and ECG,
      results can be considered very promising as instantaneous sympatho-vagal changes
      were correctly identified. More research is indeed needed to improve on the
      precise estimation of nonlinear sympatho-vagal interactions.

PMID- 29060233
TI  - Towards VO2 monitoring: Validation of a heart rate based algorithm.
AB  - This article presents and validates a novel algorithm for the continuous
      monitoring of the VO2 during exercise. The algorithm relies on instantaneous HR
      measurements to provide a continuous estimation, and can be integrated in a
      wearable device (e.g., smartwatch, sensor patch). It can be customized by user's
      main anthropomorphic parameters and automatically learns from newly incoming data
      recalibrating itself if needed. The system is evaluated against a database of 14
      healthy subjects performing various maximal endurance tests. The proposed method
      provides a VO2 estimation with average RMSE of 4.63 ml/kg/min.

PMID- 29060234
TI  - A portable platform to collect and review behavioral data simultaneously with
      neurophysiological signals.
AB  - This paper presents a portable platform to collect and review behavioral data
      simultaneously with neurophysiological signals. The whole system is comprised of
      four parts: a sensor data acquisition interface, a socket server for real-time
      data streaming, a Simulink system for real-time processing and an offline data
      review and analysis toolbox. A low-cost microcontroller is used to acquire data
      from external sensors such as accelerometer and hand dynamometer. The micro
      controller transfers the data either directly through USB or wirelessly through a
      bluetooth module to a data server written in C++ for MS Windows OS. The data
      server also interfaces with the digital glove and captures HD video from webcam.
      The acquired sensor data are streamed under User Datagram Protocol (UDP) to other
      applications such as Simulink/Matlab for real-time analysis and recording.
      Neurophysiological signals such as electroencephalography (EEG),
      electrocorticography (ECoG) and local field potential (LFP) recordings can be
      collected simultaneously in Simulink and fused with behavioral data. In addition,
      we developed a customized Matlab Graphical User Interface (GUI) software to
      review, annotate and analyze the data offline. The software provides a fast, user
      friendly data visualization environment with synchronized video playback feature.
      The software is also capable of reviewing long-term neural recordings. Other
      featured functions such as fast preprocessing with multithreaded filters,
      annotation, montage selection, power-spectral density (PSD) estimate, time
      frequency map and spatial spectral map are also implemented.

PMID- 29060235
TI  - A simple, remote, video based breathing monitor.
AB  - Breathing monitors have become the all-important cornerstone of a wide variety of
      commercial and personal safety applications, ranging from elderly care to baby
      monitoring. Many such monitors exist in the market, some, with vital signs
      monitoring capabilities, but none remote. This paper presents a simple, yet
      efficient, real time method of extracting the subject's breathing sinus rhythm.
      Points of interest are detected on the subject's body, and the corresponding
      optical flow is estimated and tracked using the well known Lucas-Kanade algorithm
      on a frame by frame basis. A generalized likelihood ratio test is then utilized
      on each of the many interest points to detect which is moving in harmonic
      fashion. Finally, a spectral estimation algorithm based on Pisarenko harmonic
      decomposition tracks the harmonic frequency in real time, and a fusion maximum
      likelihood algorithm optimally estimates the breathing rate using all points
      considered. The results show a maximal error of 1 BPM between the true breathing
      rate and the algorithm's calculated rate, based on experiments on two babies and
      three adults.

PMID- 29060236
TI  - On the use of higher-order tensors to model muscle synergies.
AB  - The muscle synergy concept provides the best framework to understand motor
      control and it has been recently utilised in many applications such as prosthesis
      control. The current muscle synergy model relies on decomposing multi-channel
      surface Electromyography (EMG) signals into a synergy matrix (spatial mode) and
      its weighting function (temporal mode). This is done using several matrix
      factorisation techniques, with Non-negative matrix factorisation (NMF) being the
      most prominent method. Here, we introduce a 4th-order tensor muscle synergy model
      that extends the current state of the art by taking spectral information and
      repetitions (movements) into account. This adds more depth to the model and
      provides more synergistic information. In particular, we illustrate a proof-of
      concept study where the Tucker3 tensor decomposition model was applied to a
      subset of wrist movements from the Ninapro database. The results showed the
      potential of Tucker3 tensor factorisation in finding patterns of muscle synergies
      with information about the movements and highlights the differences between the
      current and proposed model.

PMID- 29060237
TI  - Exploring optimal myoelectric feature indices for forearm control strategy using
      robust principal component analysis.
AB  - Forearm movements realize various functions needed in daily life. For
      reproduction of the motion sequences, active myoelectric devices have been
      developed. Usually, feature indices are extracted from observed signals in
      control strategy; however, the optimal combination of indices is still unclear.
      This paper introduces sparsity-inducing penalty term in principal component
      analysis (PCA) to explore optimal myoelectric feature indices. An
      electromyographic database including seven forearm movements from 30 subjects was
      used for performance comparison. Linear classifier with sparse features showed
      best performance (7.86+/-3.82% error rate) that was significantly better than
      linear classifier with all features because of recovering low rank matrix in
      original data. Furthermore, the sparse features had a large contribution of
      underlying data structure with less number of principal components than PCA. Root
      mean-square, time-domain features, autoregressive coefficients, and Histogram
      purported to be important in projected feature space; therefore, the feature
      indices are important to myoelectric strategies.

PMID- 29060238
TI  - Coupling Scatter Correction with bandpass filtering for preprocessing in the
      quantitative analysis of glucose from near infrared spectra.
AB  - This paper proposes a novel pre-processing method based on combining bandpass
      filtering with scatter correction techniques Multiplicative Scatter Correction
      (MSC) and Standard Normal Variate (SNV) to enhance the prediction capability of
      the linear regression models Partial Least Squares Regression (PLSR) and
      Principal Component Regression (PCR) in near infrared (NIR) spectroscopy. The
      method is implemented into a calibration model, evaluated and then validated for
      the prediction of the glucose concentration from NIR spectra of an aqueous
      mixture of human serum albumin and glucose in a solution of distilled water and
      phosphate buffer. The results obtained demonstrate improved prediction
      performance for both PCR and PLSR. Compared to the efficient feature weighting
      pre-processing (RRelief), the proposed method is shown to yield better prediction
      reducing the Root Mean Square Error Prediction RMSEP.

PMID- 29060239
TI  - Modified thresholding technique of MMSPCA for extracting respiratory activity
      from short length PPG signal.
AB  - In this paper, we propose an automatic threshold selection of modified multi
      scale principal component analysis (MMSPCA) for reliable extraction of
      respiratory activity (RA) from short length photoplethysmographic (PPG) signals.
      MMSPCA was applied to the PPG signal with a varying data length, from 30 seconds
      to 60 seconds, to extract the respiratory activity. To examine the performance,
      we used 100 epochs of simultaneously recorded PPG and respiratory signals
      extracted from the MIMIC database (Physionet ATM data bank). The respiratory
      signal used as the ground truth and several performance measurement metrics such
      as magnitude squared coherence (MSC), correlation coefficients (CC), and
      normalized root mean square error (NRMSE) were used to compare the performance of
      MMSPCA based PPG derived RA. At the data length of 30 seconds, MSC, CC and NRMSE
      for proposed thresholding were 0.65, 0.62 and -0.82 dB respectively where as they
      were 0.68, 0.47 and 0.25 dB respectively for existing thresholding. These results
      illustrated that the proposed threshold selection performs better than existing
      threshold selection for short length data.

PMID- 29060240
TI  - Channels selection using independent component analysis and scalp map projection
      for EEG-based driver fatigue classification.
AB  - This paper presents a classification of driver fatigue with
      electroencephalography (EEG) channels selection analysis. The system employs
      independent component analysis (ICA) with scalp map back projection to select the
      dominant of EEG channels. After channel selection, the features of the selected
      EEG channels were extracted based on power spectral density (PSD), and then
      classified using a Bayesian neural network. The results of the ICA decomposition
      with the back-projected scalp map and a threshold showed that the EEG channels
      can be reduced from 32 channels into 16 dominants channels involved in fatigue
      assessment as chosen channels, which included AF3, F3, FC1, FC5, T7, CP5, P3, O1,
      P4, P8, CP6, T8, FC2, F8, AF4, FP2. The result of fatigue vs. alert
      classification of the selected 16 channels yielded a sensitivity of 76.8%,
      specificity of 74.3% and an accuracy of 75.5%. Also, the classification results
      of the selected 16 channels are comparable to those using the original 32
      channels. So, the selected 16 channels is preferable for ergonomics improvement
      of EEG-based fatigue classification system.

PMID- 29060241
TI  - Motion artifact reduction in photoplethysmogram signals based on Periodic
      Component Factorization.
AB  - Continuous blood pressure measurement based on pulse transit time (PTT) is a
      deeply research topic over recent decades. Advanced algorithms have been proposed
      by scholars to give satisfactory estimation in stationary position. Nevertheless,
      pulse transit time (PTT) is shown to be strongly affected by hand movement and
      the estimation of blood pressure is no longer accurate under strenuous exercise.
      Because of this, a novel algorithm called Periodic Component Factorization (PCF),
      which is an extension of Independent Component Analysis (ICA), for better removal
      of motion artifact (MA) from photoplethysmography (PPG) signals is proposed in
      this paper. Compared to FastICA algorithm based on nongaussianity such as
      kurtosis and skewness, PCF is able to extract dependent source components from
      noisy signals when the PPG signal shows quasi-periodicity or periodicity. This
      newly proposed algorithm undoubtedly shows its practicality and effectiveness in
      removing motion artifact of PPG signals.

PMID- 29060242
TI  - Interactive patient-specific 3D approximation of scapula bone shape from 2D X-ray
      images using landmark-constrained statistical shape model fitting.
AB  - We report on an interactive tool for patientspecific 3D approximation of scapula
      bone shape from 2D X-ray images using landmark-constrained statistical shape
      model (SSM) fitting. The 3D localization of points on the 2D X-ray images was
      done through X-ray stereophotogrammetry. The inferior angle, acromion and the
      coracoid process were identified as reliable landmarks from the anteroposterior
      (AP) and oblique lateral views in a landmark selection study. The 3D scapula
      surface was approximated through fitting the scapula SSM to the 3D reconstructed
      coordinates of the selected landmarks. 3D point localization yielded average (X,
      Y, Z) coordinate reconstruction errors of (X=0.14, Y=0.07, Z=0.04) mm. The
      landmark-constrained fitting algorithm yielded an average error between the mean
      posterior model landmarks and the corresponding target landmarks of 0.49 mm using
      the three landmarks, and later 0.19 mm with sixteen landmarks. Average surface to
      surface error between the CT ground truth model and approximated model from
      within the dataset improved from 3.20 mm to 2.46 mm using three landmarks and
      using sixteen landmarks, respectively. Average surface to surface error between
      the CT ground truth model and the approximated model from outside the dataset
      improved from 4.28 mm to 3.20 mm using three landmarks and using sixteen
      landmarks, respectively.

PMID- 29060243
TI  - Arytenoid cartilage feature point detection using laryngeal 3D CT images in
      Parkinson's disease.
AB  - Parkinson's disease is a neurodegenerative disorder that results in progressive
      degeneration of nerve cells. It is generally associated with the deficiency of
      dopamine, a neurotransmitter involved in motor control of humans and thus affects
      the motor system. This results in abnormal vocal fold movements in majority of
      the Parkinson's patients. Analysis of vocal fold abnormalities may provide useful
      information to assess the progress of Parkinson's disease. This is accomplished
      by measuring the distance between the arytenoid cartilages during phonation. In
      order to automate this process of identifying arytenoid cartilages from CT
      images, in this work, a rule-based approach is proposed to detect the arytenoid
      cartilage feature points on either side of the airway. The proposed technique
      detects feature points by localizing the anterior commissure and analyzing airway
      boundary pixels to select the optimal feature point based on detected pixels. The
      proposed approach achieved 83.33% accuracy in estimating clinically-relevant
      feature points, making the approach suitable for automated feature point
      detection. To the best of our knowledge, this is the first such approach to
      detect arytenoid cartilage feature points using laryngeal 3D CT images.

PMID- 29060244
TI  - Multiple mucociliary transit marker tracking in synchrotron X-ray images using
      the global nearest neighbor method.
AB  - Recent research has enabled in-vivo examination of mucociliary transit in live
      airways by analysing the movement patterns of micron-sized markers in high
      resolution synchrotron X-ray images. However, high levels of false positives and
      false negatives severely impact the performance of many automated tracking
      algorithms. This paper proposes an improved approach to track valid mucociliary
      transit markers using a modified gating region and cost matrix. The proposed
      method offers a more effective way to associate markers with the correct
      trackers. Improved visualization methods are also introduced to assist the
      interpretation of the tracking results. The tracking method has achieved a
      tracking accuracy of 81.7% track purity and 71.3% track effectiveness.

PMID- 29060245
TI  - A one-dimensional fluid simulation method of branching narrow vessel for real
      time angiography simulation.
AB  - This paper proposes a one-dimensional fluid simulation method for real-time
      simulation of the contrast medium in a narrow blood vessel. A narrow vessel is
      modeled with the branches organized in a hierarchy. The density of the contrast
      medium on each branch is computed using the one-dimensional fluid model. The
      density at the last point of branch is conveyed to the first point of the
      following branches. The position of the density computation is determined to
      continuously convey the simulation results from a large vessel to a narrow
      vessel. The average computation time with the proposed method is 16.18 ms that is
      less than 21.25 ms of the particle-based method.

PMID- 29060246
TI  - The use of subject-specific Finite Element analysis of L1-L4 vertebra to
      screening osteoporosis in postmenopausal women.
AB  - The aim of this work is to study Computed Tomography (CT)-based Finite Element
      (FE) modelling of lumbar vertebra to classify osteoporotic patients using dual
      energy x-ray absorptiometry (DXA) as reference. Cohort comprised 15
      postmenopausal female patients with CT-DXA pairs. Sixty subject-specific CT-based
      FE models were constructed of L1 to L4 vertebrae. Load-displacement in each node
      of the models was analyzed. Mean kurtosis values of displacement distributions
      between osteoporosis and healthy groups at L1 level showed a statistically
      significant difference (p<;0.005). The CT-based FE model of L1 vertebra with
      patient specific material properties can be used to identify osteoporosis
      patients.

PMID- 29060247
TI  - Environment effects at phantom-based X-ray pose measurements.
AB  - Image-based pose measurements relative to phantoms are used for various
      applications. Some examples are: tracking, registration or calibration. If highly
      precise measurements are needed, even changes of environment factors influence
      the measurements.

PMID- 29060248
TI  - Development of an intraluminal intestinal photoplethysmography sensor.
AB  - Intestinal ischemia is a serious medical condition and can lead to life
      threatening sepsis. Currently, there are no reliable techniques available for
      directly monitoring intestinal viability for prolonged periods of time, and
      intraoperatively, the majority of the surgeons still rely on subjective methods,
      such as visual inspection to assess viability of the intestine. The development
      of an intraluminal optical sensor for monitoring intestinal viability is being
      proposed. The sensor will continuously monitor changes in blood volume and oxygen
      saturation. The developed reflectance photoplethysmography/pulse oximetry sensor
      comprises of two emitters (red and infrared) and a photodiode. A
      photoplethysmography processing and data acquisition system was also utilized.
      The prototype sensor was evaluated in a pilot study in the buccal mucosa of 12
      healthy volunteers, given the locations similarity to the intestinal mucosa and
      its easy accessibility. Good quality photoplethysmography signals with high
      signal-to-noise ratio were acquired from the buccal mucosa in all the volunteers.
      Preliminary blood oxygen saturation values from the intraluminal sensor were in
      broad agreement with the standard finger pulse oximeter probes.

PMID- 29060249
TI  - Instrumentation, electrode choice and challenges in human skin memristor
      measurement.
AB  - Recording of the passive electrical properties of human skin is a well
      established method in clinical applications and research. By applying a small
      constant voltage or current to the skin, its conductance can be determined
      without changing it. If a strong electrical signal is applied, the conductance
      can change. In fact, such nonlinear effects in skin can be observed and it has
      been shown that the skin acts like a memristor. These nonlinear properties of
      human skin are not studied systematically yet and hence represent a new field of
      research. This paper presents a measurement system that is suitable for doing
      human skin memristor measurements including hardware, electrode choice and
      aspects that have to be considered.

PMID- 29060250
TI  - Flexible organic TFT bio-signal amplifier using reliable chip component assembly
      process with conductive adhesive.
AB  - This paper presents a flexible organic thin-film transistor (OTFT) amplifier for
      bio-signal monitoring and presents the chip component assembly process. Using a
      conductive adhesive and a chip mounter, the chip components are mounted on a
      flexible film substrate, which has OTFT circuits. This study first investigates
      the assembly technique reliability for chip components on the flexible substrate.
      This study also specifically examines heart pulse wave monitoring conducted using
      the proposed flexible amplifier circuit and a flexible piezoelectric film. We
      connected the amplifier to a bluetooth device for a wearable device
      demonstration.

PMID- 29060251
TI  - Continuous systolic and diastolic blood pressure estimation utilizing long short
      term memory network.
AB  - A novel blood pressure estimation method based on long short-term memory neural
      network, one of the recurrent neural networks being commonly used nowadays, is
      proposed in this paper for better chronic diseases monitoring. Along with the
      neural network, a newly proposed ambulatory blood pressure (ABP) processing
      technique called Two-stage Zero-order Holding (TZH) algorithm has also been
      presented in the paper. The proposed methodology has the advantages over
      traditional blood pressure estimation algorithms which are based on Pulse Transit
      time (PTT). The paper addresses the effectiveness of the algorithm by computing
      the Root-Mean-Squared Errors (RMSE) between the BP estimated and the ground
      truth. Our algorithm shows precise systolic blood pressure and diastolic blood
      pressure estimation with the average RMSE values in 2.751 mmHg and 1.604 mmHg
      respectively across the sample used. Experimental results suggest that BP
      estimation based on LSTM has great potential to be embedded into monitoring
      system for better accuracy and generalization.

PMID- 29060252
TI  - An in vivo MEMS sensor system for percutaneous measurement of urinary bladder.
AB  - An in vivo sensor system for direct measurement of pressure in the human urinary
      bladder is developed. The core component in the system is a small-sized and
      highly sensitive piezoresistive MEMS pressure sensor element integrated in a
      sensor catheter. The sensor catheter is wired to an external module for biasing,
      sampling, conversion and storage of sensor measurements. Our solution provides a
      target sensor placed directly into the urinary bladder and a reference sensor
      placed outside the bladder wall through a suprapubic and minimally invasive
      technique. Physiological recordings through natural filling and emptying cycles
      of the bladder are achievable. The case report from the first 17-hours
      investigation in a patient is presented in this paper. It reveals that the
      procedure was successful and no complications occurred. The patient expressed
      good experience during the participation. A functionality test shows that the
      percutaneous pressure sensor system responds immediately to external pressure
      stimuli.

PMID- 29060253
TI  - Performance assessment of dry electrodes for wearable long term cardiac rhythm
      monitoring: Skin-electrode impedance spectroscopy.
AB  - The use of wearable dry sensors for recording long term ECG signals is a
      requirement for certain studies of heart rhythm. Knowledge of the skin-electrode
      electrical performance of dry electrodes is necessary when seeking to improve
      various processing stages for signal quality enhancement. In this paper, methods
      for the assessment of dry skin-electrode impedance (ZSE) and its modelling are
      presented. Measurements were carried out on selected electrode materials such as
      silver, stainless steel, AgCl (dry) and polyurethane. These had ZSE values
      between 500 kOmega and 1 MOmega within the main ECG frequency range (1 Hz - 100
      Hz); in contrast to plain iron material which had a significantly higher
      impedance. However, in spite of the high ZSE values, open bandwidth ECG traces
      were of acceptable quality and stability; with dry AgCl material offering the
      best ECG trace performance.

PMID- 29060254
TI  - Protein patterning using germanium as a sacrificial layer.
AB  - With the rise of microfluidic diagnostics, there is a need for more efficient
      methods of patterning surface-attached moieties, including proteins like
      antibodies, onto microchannel surfaces. This arises because almost all of the
      solvents and processes used for surface-attachment chemistries (or their
      payloads) are incompatible with sacrificial layers usually photoresist during
      microfabrication, rendering it difficult to easily pattern active chemistry onto
      a surface in manufacture scale. We present a simple method, based on thin film
      germanium dissolution, which is compatible with both modern nanolithographic
      techniques and surface chemistries. Simply, because germanium thin films dissolve
      readily, controllably and rapidly in water (but not organic solvents), these
      films can be used to mask and protect areas of the substrate during the
      attachment of surface chemistries. We demonstrate the process and results using
      microscale patterns. The resolution and alignment of this method depends on the
      photolithography tool used; nanoscale patterning is not difficult to achieve. In
      addition, we show that with non-conformal germanium deposition (e.g. e-beam
      evaporation), the conjugation of surface chemistry on vertical side walls can be
      manipulated by controlling the thickness of the deposited germanium layer,
      opening another dimension for microfluidic devices and cell manipulation
      research.

PMID- 29060255
TI  - Conducting polymer microcontainers for biomedical applications.
AB  - Advancement in the development of metallic-based implantable micro-scale
      bioelectronics has been limited by low signal to noise ratios and low charge
      injection at electrode-tissue interfaces. Further, implantable electrodes lose
      their long-term functionality because of unfavorable reactive tissue responses.
      Thus, substantial incentive exists to produce bioelectronics capable of
      delivering therapeutic compounds while improving electrical performance. Here, we
      have produced hollow poly(pyrrole) microcontainers (MCs) using poly(lactic-co
      glycolic) acid (PLGA) as degradable templates. We demonstrate that the effective
      surface area of the electrode increases significantly as deposition charge
      density is increased, resulting in a 91% decrease in impedance and an 85%
      increase in charge storage capacity versus uncoated gold electrodes. We also
      developed an equivalent circuit model to quantify the effect of conducting
      polymer film growth on impedance. These MC-modified electrodes offer the
      potential to improve the electrical properties of implantable bioelectronics, as
      well as provide potential controlled release avenues for drug delivery
      applications.

PMID- 29060256
TI  - Mechanical properties of triply periodic minimal surface structures mimicking the
      microstructure of Woodpecker's cranial bone.
AB  - A new triply periodic minimal surface (TPMS) structure mimicking the
      microstructure of Great Spotted Woodpecker's cranial bone was designed,
      fabricated and tested in this study. It was found that the designed structures
      acquired better mechanical performance compared to the unit structures applied in
      heterogeneous porous scaffolds. The wall thickness mimicking the woodpecker's
      spongy bone and the TPMS surface structure were two contributors to the good
      mechanical performance of new designed bionic structures.

PMID- 29060257
TI  - Self-spreading method for forming lipid bilayer on a patterned agarose gel:
      Toward precise lipid bilayer patterning.
AB  - Forming artificial cell membranes is a suitable strategy for studying drug
      responses of membrane proteins. In order to form lipid bilayer with both
      mechanical stability and membrane protein functions, hydrogel supported bilayer
      has attracted attentions. Combinational use of self-extraction method for lipid
      bilayer formation and agarose gel patterning should realize hydrogel-supported
      bilayer with any shape and large area. In this study, we aimed to form a lipid
      bilayer on a patterned agarose gel and to characterize the membrane. First, lipid
      mixture was attached on an agarose gel, and lipid layers spread on the gel
      surface. With fluorescent observation, it is suggested that thin lipid layer was
      formed on the agarose gel, and their distance-dependent changes in spreading
      velocity was consistent with that in lipid bilayer. Next, the lipid layer was
      characterized with fluorescence recovery after photo breaching experiment. As a
      result, it is indicated that lipid molecules in the lipid layer on the agarose
      showed lateral diffusion, a typical characteristic of lipid bilayer. Taken
      together, we confirmed that lipid bilayer can be formed on the patterned agarose
      gel with self-spreading method. The hydrogel-supported bilayer will be a suitable
      tool for drug discovery.

PMID- 29060258
TI  - Tunable nanostructured conducting polymers for neural interface applications.
AB  - Advancement in the development of traditional metallic-based implantable
      electrodes for neural interfacing has reached a plateau in recent years in terms
      of their ability to provide safe, long-term, and high resolution stimulation
      and/or recording. The reduction of electrode size enables higher selectivity
      through increased electrodes per implant device; however, it also results in
      lower sensitivity at electrode-tissue interfaces. This limitation can be
      addressed through the utilization of conducting polymer (CP) coatings, which
      increase the effective surface area. In this work, we investigate the surface
      roughness of two common conducting polymers; poly(pyrrole) (PPy) and poly(3,4
      ethylenedioxythiophene) (PEDOT) in the form of films deposited using both
      potentiostatic (PSTAT) and galvanostatic (GSTAT) methods. We found that the
      surface roughness of both CP films can be increased by over 90% through control
      of both deposition time and applied electrical deposition (current for GSTAT and
      voltage for PSTAT). The impedance of PPy-modified electrodes was found to
      decrease by up to 88%. This study shows that the surface roughness of CPs can be
      modulated to control electrical properties of neural electrodes and may improve
      the cellular response of neurons.

PMID- 29060259
TI  - Simple and fast polydimethylsiloxane (PDMS) patterning using a cutting plotter
      and vinyl adhesives to achieve etching results.
AB  - Inhibition of polydimethylsiloxane (PDMS) polymerization could be observed when
      spin-coated over vinyl substrates. The degree of polymerization, partially curing
      or fully curing, depended on the PDMS thickness coated over the vinyl substrate.
      This characteristic was exploited to achieve simple and fast PDMS patterning
      method using a vinyl adhesive layer patterned through a cutting plotter. The
      proposed patterning method showed results resembling PDMS etching. Therefore,
      patterning PDMS over PDMS, glass, silicon, and gold substrates were tested to
      compare the results with conventional etching methods. Vinyl stencils with widths
      ranging from 200MUm to 1500MUm were used for the procedure. To evaluate the
      accuracy of the cutting plotter, stencil designed on the AutoCAD software and the
      actual stencil widths were compared. Furthermore, this method's accuracy was also
      evaluated by comparing the widths of the actual stencils and etched PDMS results.

PMID- 29060260
TI  - Human locomotion analysis: Identifying a dynamic mapping between upper and lower
      limb joints using the Koopman operator.
AB  - Human locomotion is a complex process that shows some inherent synergies and
      coordination, also called inter-joint coordination, between the upper and lower
      limbs. In this paper, we investigate the use of Koopman operator to identify a
      dynamic mapping between an upper limb and its contra-lateral lower limb in the
      human locomotion. We perform a human locomotion analysis in the sagittal plane
      and restrict the study to the forward motion; more specifically, a straight
      walking task at a constant speed. We use canes as walking aids to provide
      additional information about the terrain and enforce a frequency locking between
      the upper and lower body. This mapping will provide a model of the human
      locomotion.

PMID- 29060261
TI  - Fusing motion-capture and inertial measurements for improved joint state
      recovery: An application for sit-to-stand actions.
AB  - The estimate of joint angles, velocities, and accelerations is a key component of
      biomechanical modelling. The literature presents a variety of sensing modalities
      and algorithms to recover the full joint state, with tuning parameters varying
      between different applications, actions, and limbs. Comparisons between these
      methods are frequently limited to angles only, without comparison between the
      joint velocities and accelerations. This paper introduces an algorithm to fuse
      motion-capture and inertial measurements to recover the full state during a sit
      to-stand task. This algorithm is then compared to three other methods: Kalman
      filtering on motion-capture or inertial measurements alone and the standard
      angular recovery/differentiation method. It is shown that the fusion of both
      optical and inertial measurements reduce the ripple and offset artefacts which
      become pronounced in high acceleration human motions.

PMID- 29060262
TI  - Quantifying the effects of on-the-fly changes of seating configuration on the
      stability of a manual wheelchair.
AB  - In general, manual wheelchairs are designed with a fixed frame, which is not
      optimal for every situation. Adjustable on the fly seating allow users to rapidly
      adapt their wheelchair configuration to suit different tasks. These changes move
      the center of gravity (CoG) of the system, altering the wheelchair stability and
      maneuverability. To assess these changes, a computer simulation of a manual
      wheelchair was created with adjustable seat, backrest, rear axle position and
      user position, and validated with experimental testing. The stability of the
      wheelchair was most affected by the position of the rear axle, but adjustments to
      the backrest and seat angles also result in stability improvements that could be
      used when wheeling in the community. These findings describe the most influential
      parameters for wheelchair stability and maneuverability, as well as provide
      quantitative guidelines for the use of manual wheelchairs with on the fly
      adjustable seats.

PMID- 29060263
TI  - Simulation of oxygen uptake and leg joint reaction force during ergometer
      exercise under altered gravity.
AB  - Ergometers are safe devices for patients and elderly individuals, as the exercise
      intensity can be controlled. Moreover, ergometer exercises, which remove the load
      from body weight on the leg joint, would better reflect training conditions in
      locations where the force of gravity is lower than that on Earth, such as the
      International Space Station or on the surface of Mars. The purpose of this study
      was not only to validate an ergometer exercise model for measuring oxygen uptake
      and knee joint reaction force by comparison with experimental results, but also
      to consider a strategy for electrically stimulating leg joint muscles to modulate
      them under altered gravity.

PMID- 29060264
TI  - Analysis of gait pattern during stair walk for improvement of gait training
      robot.
AB  - This paper seeks stair gait patterns which can improve effectiveness of gait
      training by applying to robotic locomotion therapy system. To get applicable data
      for stair walking function of the system, the stair walk of five subjects were
      measured by a motion capture system. From the acquired data, trajectories of each
      joint angle and relative change of the joints were calculated in the anatomical
      sagittal plane. Also, we were attempt to create more natural stair gait pattern
      by analyzing the movement of hip on the transverse plane.

PMID- 29060265
TI  - Body pose estimation in depth images for infant motion analysis.
AB  - Motion analysis of infants is used for early detection of movement disorders like
      cerebral palsy. For the development of automated methods, capturing the infant's
      pose accurately is crucial. Our system for predicting 3D joint positions is based
      on a recently introduced pixelwise body part classifier using random ferns, to
      which we propose multiple enhancements. We apply a feature selection step before
      training random ferns to avoid the inclusion of redundant features. We introduce
      a kinematic chain reweighting scheme to identify and to correct misclassified
      pixels, and we achieve rotation invariance by performing PCA on the input depth
      image. The proposed methods improve pose estimation accuracy by a large margin on
      multiple recordings of infants. We demonstrate the suitability of the approach
      for motion analysis by comparing predicted knee angles to ground truth angles.

PMID- 29060266
TI  - Electrocortical amplitude modulations of human level-ground, slope, and stair
      walking.
AB  - This study investigates if the electrocortical amplitude modulations relative to
      the mean gait cycle are different across walking conditions (i.e., level-ground
      (LW), ramp ascent (RA), and stair ascent (SA)). Non-invasive
      electroencephalography (EEG) signals were recorded and a systematic EEG
      processing method was implemented to reduce artifacts. Source localization using
      independent component analysis and k-means clustering revealed the involvement of
      four clusters in the brain (Left and Right Occipital Lobe, Posterior Parietal
      Cortex (PPC), and Sensorimotor Area) during the walking tasks. We found that
      electrocortical amplitude modulations varied across different walking conditions.
      Specifically, our results showed that the modulations in the PPC shifted to
      higher frequency bands when the subjects walked in RA and SA conditions.
      Moreover, we found low gamma modulations in the sensorimotor area in LW walking
      and the modulations in this cluster shifted to lower frequency bands in RA and SA
      walking. These results are a promising step toward the development of a non
      invasive Neural-machine Interface (NMI) for locomotion mode recognition.

PMID- 29060267
TI  - EEG-guided robotic mirror therapy system for lower limb rehabilitation.
AB  - Lower extremity function recovery is one of the most important goals in stroke
      rehabilitation. Many paradigms and technologies have been introduced for the
      lower limb rehabilitation over the past decades, but their outcomes indicate a
      need to develop a complementary approach. One attempt to accomplish a better
      functional recovery is to combine bottom-up and top-down approaches by means of
      brain-computer interfaces (BCIs). In this study, a BCI-controlled robotic mirror
      therapy system is proposed for lower limb recovery following stroke. An
      experimental paradigm including four states is introduced to combine robotic
      training (bottom-up) and mirror therapy (top-down) approaches. A BCI system is
      presented to classify the electroencephalography (EEG) evidence. In addition, a
      probabilistic model is presented to assist patients in transition across the
      experiment states based on their intent. To demonstrate the feasibility of the
      system, both offline and online analyses are performed for five healthy subjects.
      The experiment results show a promising performance for the system, with average
      accuracy of 94% in offline and 75% in online sessions.

PMID- 29060268
TI  - Boosting performance in brain-machine interface by classifier-level fusion based
      on accumulative training models from multi-day data.
AB  - The nonstationarity of neural signal is still an unresolved issue despite the
      rapid progress made in brain-machine interface (BMI). This paper investigates how
      to utilize the rich information and dynamics in multi-day data to address the
      variability in day-to-day signal quality and neural tuning properties. For this
      purpose, we propose a classifier-level fusion technique to build a robust
      decoding model by jointly considering the classifier outputs from multiple base
      training models using multi-day data collected prior to test day. The data set
      used in this study consisted of recordings of 8 days from a non-human primate
      (NHP) during control of a mobile robot using a joystick. Offline analysis
      demonstrates the superior performance of the proposed method which results in
      4.4% and 13.10% improvements in decoding (significant by one-way ANOVA and post
      hoc t-test) compared with the two baseline methods: 1) concatenating data from
      multiple days based on common effective channels, and 2) averaging accuracies
      across all base-training models. These results further validate the effectiveness
      of proposed method without recalibration of the model.

PMID- 29060269
TI  - Stop state classification in intracortical brain-machine-interface.
AB  - Invasive brain-machine-interface (BMI) has the prospect to empower tetraplegic
      patients with independent mobility through the use of brain-controlled
      wheelchairs. For the practical and long-term use of such control systems, the
      system has to distinguish between stop and movement states and has to be robust
      to overcome non-stationarity in the brain signals. In this work, we investigates
      the non-stationarity of the stop state on neural data collected from a macaque
      trained to control a robotic platform to stop and move in left, right, forward
      directions We then propose a hybrid approach that employs both random forest and
      linear discriminant analysis (LDA). Using this approach, we performed offline
      decoding on 8 days of data collected over the course of three months during
      joystick control of the robotic platform. We compared the results of using the
      proposed approach with the use of LDA alone to perform direct classifications of
      stop, left, right and forward. The results showed an average performance
      increment of 22.7% using the proposed hybrid approach. The results yielded
      significant improvements during sessions where LDA showed a heavy bias towards
      the stop state. This suggests that the proposed hybrid approach addresses the non
      stationarity in the stop state and subsequently facilitates a more accurate
      decoding of the movement states.

PMID- 29060270
TI  - A frequency recognition method based on multitaper spectral analysis and SNR
      estimation for SSVEP-based brain-computer interface.
AB  - Over the past several years, steady-state visual evoked potential (SSVEP)-based
      brain-computer interfaces (BCIs) have attracted wide attention in the field of
      BCIs research due to high information transfer rate, little user training, and
      applicability to the majority. In conventional recognition methods for training
      free SSVEP-based BCIs, the energy difference between the frequencies of
      electroencephalogram (EEG) background noise is usually ignored, therefore, there
      is a significant variance among the recognition accuracy of different stimulus
      frequencies. In order to improve the performance of training-free SSVEP-based
      BCIs system and balance the accuracy of recognition between different stimulus
      frequencies, a recognition method based on multitaper spectral analysis and
      signal-to-noise ratio estimation (MTSA-SNR) is proposed in this paper. A 40-class
      SSVEP public benchmark SSVEP dataset recorded from 35 subjects was used to
      evaluate the performance of the proposed method. Under the condition of 2.25s
      data length, the accuracy of the three methods were 81.1% (MTSA-SNR), 74.5%
      (canonical correlation analysis, CCA) and 73.4% (multivariate synchronization
      index, MSI), and the corresponding ITRs were 101 bits/min (MTSA-SNR), 89 bits/min
      (CCA), 87 bits/min (MSI). In the low frequency range (8-9.8Hz), the average
      recognition accuracy of the three methods is 82.9% (MTSA-SNR), 82.0% (CCA), 83.3%
      (MSI). The average accuracy of the three methods was 78.6% (MTSA-SNR), 64.9%
      (CCA) and 61.8% (MSI) in the high frequency range (14-15.8Hz). According to the
      results, the proposed method can effectively improve the performance of training
      free SSVEP-based BCI system, and balance the recognition accuracy between
      different stimulation frequencies.

PMID- 29060271
TI  - Learning to control an SSVEP-based BCI speller in naive subjects.
AB  - High-speed steady-state visual evoked potential (SSVEP)-based brain-computer
      interface (BCI) has been demonstrated in several recent studies. This study aimed
      to investigate some issues regarding feasibility of learning to control an SSVEP
      based BCI speller in naive subjects. An experiment with new BCI users was
      designed to answer the following questions: (1) How many people can use the SSVEP
      BCI speller? (2) How much time is required to train the user? (3) Does continuous
      system use lead to user fatigue and deteriorated BCI performance? The experiment
      consisted of three tasks including a 40-class BCI spelling task, a psychomotor
      vigilance test (PVT) task, and a test of sleepiness scale. Subjects' reaction
      time (RT) in the PVT task and the fatigue rank in the sleepiness scale test were
      used as objective and subjective parameters to evaluate subjects' alertness
      level. Among 11 naive subjects, 10 of them fulfilled the 9-block experiment. Four
      of them showed clear learning effects (i.e., an increasing trend of
      classification accuracy and information transfer rate (ITR)) over time. The
      remaining subjects showed stable BCI performance during the whole experiment. The
      results of RT and fatigue rank showed a gradually increasing trend, which is not
      significant across blocks. In summary, the results of this study suggest that
      controlling an SSVEP-based BCI speller is in general feasible to learn by naive
      subjects after a short training procedure, showing no clear performance
      deterioration related to fatigue.

PMID- 29060272
TI  - A 64-channels neural interface for biopotentials recording and PNS stimulation.
AB  - A biomedical interface that combines into a single and compact device the
      recording of biopotentials and the electrical stimulation of neural fibres is
      presented. It is intended for enabling the control over a robotic hand and for
      restoring the sensory feedback in amputees by directly interfacing the peripheral
      nervous system (PNS) in closed-loop. A modular system consisting in one or more
      independent 16-channels bidirectional units was conceived. Each module is based
      on three 0.35MUm bulk-CMOS integrated circuits (ICs): a recording unit, a High
      Voltage (HV) stimulator and a HV booster. A tunable bandwidth (10Hz-8kHz) allows
      the recording IC to acquire both electroneurographyc (ENG) and electromiographyc
      (EMG) signals with a programmable gain up to 43.5dB. The signals are then
      converted into a digital domain by means of a SigmaDelta converter. Due to the
      typical high impedance at the electrode-tissue interface, a programmable HV
      booster that increases the stimulation voltage up to 19V was designed. It is
      directly controlled by the stimulation module that generates current-based pulses
      with a programmable amplitude and pulse-width. The whole system was validated by
      means of in-vivo experiments in rats.

PMID- 29060273
TI  - Auditory responses to short-wavelength infrared neural stimulation of the rat
      cochlear nucleus.
AB  - Pulsed Infrared laser is well-known for its high spatial resolution and contact
      free stimulation mode. In order to improve the current auditory brainstem
      implants (ABI), 980 nm-short-wavelength infrared light was applied to stimulate
      the cochlear nucleus of rats. Single neural activity from contralateral inferior
      colliculus was recorded during laser stimulation. Animal experimental results
      showed that 980 nm laser could not directly activate neurons in cochlear nucleus
      and a photo-acoustic response was observed during stimulation, however, 980 nm
      laser produces an inhibitory effect on neural responses to sounds; After we added
      carbon nanoparticles onto the surface of animal cochlear nucleus, 980 nm laser
      could directly stimulate neurons and no interference between adjacent recording
      channels was observed. These findings indicated that with the enhancement of
      carbon nanoparticles, short-wavelength infrared neural stimulation (SW-INS) might
      be an effective method to overcome the defects of current ABIs. With this method,
      a new type of optical ABI with transcutaneous stimulating method is quite
      promising.

PMID- 29060274
TI  - A computational study on effect of a transcranial channel as a skull/brain
      interface in the conventional rectangular patch-type transcranial direct current
      stimulation.
AB  - A conceptual model of a transcranial channel was recently proposed for conveying
      external currents of the skull to the brain; the effects of the transcranial
      channel combined with high-definition transcranial direct current stimulation (HD
      tDCS) was investigated, resulting in discovery of increased stimulus intensity
      and focality. In this work, rather than HD-tDCS using smaller disc-type
      electrodes, we proposed the use of the transcranial channel with conventional
      tDCS using larger patch electrodes. We used multi-scale computational models that
      couple an anatomically realistic head model with multi-compartmental models of
      cortical neurons. We then predicted the excitability in the hand knob (target
      area) based on stimulus-induced electric fields and steady-state membrane
      polarizations. Conventional tDCS without the transcranial channel resulted in
      diffuse distributions of electric fields that covered the frontal cortex, while
      the spatial focality and intensity of the excitability increased significantly at
      the target area in the presence of the transcranial channel. Thus, it is expected
      that conventional tDCS with the transcranial channel allows a better targeting
      neuromodulation with higher intensity and may be promising for applying prolonged
      and stabilized tDCS.

PMID- 29060275
TI  - Assessing rTMS effects in MdDS: Cross-modal comparison between resting state EEG
      and fMRI connectivity.
AB  - Repetitive transcranial magnetic stimulation (rTMS) has been increasingly
      explored for many neurological and neuropsychiatric conditions. However, the
      response rate is variable depending on baseline conditions. Optimizing rTMS
      protocols to improve treatment effects and response rates will depend on reliably
      assessing brain state conditions. In this regard, neural activity guided
      optimization has shown potential in several neuroimaging studies. In this paper,
      we present our ongoing work on optimizing rTMS treatment of a balance disorder
      called Mal de Debarquement Syndrome (MdDS), a motion perception disorder caused
      by entrainment to background motion. Our previous work has revealed that a
      neuroimaging marker of resting state functional connectivity may help predict
      therapeutic effect. Motivated by our previous pilot study with fMRI, the present
      study aims to extend the investigation to EEG data that were simultaneously
      acquired with fMRI, with the aim of transferring the fMRI imaging marker to a
      more accessible neural recording technology. Our current findings demonstrate
      that integrating EEG with fMRI measures of neural synchrony and functional
      connectivity may hold promise in optimizing rTMS protocols.

PMID- 29060276
TI  - Closed-loop low-frequency DBS restores thalamocortical relay fidelity in a
      computational model of the motor loop.
AB  - Closed-loop modulation of deep brain stimulation (DBS) of the subthalamic nucleus
      (STN) in Parkinson's disease (PD) is investigated to automatically adjust the
      stimulation to the patients' conditions, optimize the clinical outcomes, and
      reduce the energy requirements. This study proposes a closed-loop control system
      for real-time adaptation of the STN-DBS amplitude based on the neural activity in
      the motor thalamus. Population-averaged post-stimulus time histograms are used to
      measure the average effects of STN-DBS on the thalamocortical neurons and a L2
      norm minimization problem is solved to design the control algorithm, while the
      frequency of stimulation is kept constant. Applied on a large-scale,
      biophysically-based, anatomically-compliant model of the cortico-basal ganglia
      thalamo-cortical motor loop under PD conditions, our adaptive DBS significantly
      (P-value P<;0.05) improved the relay fidelity of the thalamocortical neurons and
      restored the average power of the thalamocortical spike trains in the band [3,
      100] Hz, two indicators of restored thalamocortical activity. Furthermore,
      adaptive-DBS significantly decreased the energy requirements when compared with
      non-adaptive-DBS at the same frequency. Finally, 30- and 60-Hz-adaptive-DBS
      determined the maximal restoration of thalamocortical activity and outperformed
      high-frequency, non-adaptive-DBS. Overall, results suggest that a feedback
      controlled, low-frequency DBS pattern may result in significant restoration of
      the thalamocortical encoding while lowering the energy requirements.

PMID- 29060277
TI  - Electric field stimulation protects injured spinal cord from secondary
      inflammatory response in rats.
AB  - OBJECTIVES: To investigate acute beneficial effects of electrical field
      stimulation (EFS) on secondary inflammatory response in spinal cord injury (SCI)
      rats. METHODS: Sprague-Dawley (SD) rats were divided into three groups,sham group
      rats received laminectomy only, control group rats were subjected to SCI only,
      and EFS group rats received EFS immediately after the injury. During the 30-min
      stimulation, the injury potential modulated to 0 +/- 0.5 mV by EFS. At 12h, 24h
      and 48h after the surgery, the rats in each group were sacrificed.
      Immunofluorescence staining for macrophage marker (ED-1), the tautomerase
      activity of macrophage inhibitory factor (MIF) assay and real-time PCR analysis
      for interleukin-1beta (IL-1beta) and matrix metalloproteinase-9 (MMP-9) were
      performed. RESULTS: Compared to the rats in control group, the rats treated with
      EFS presented less ED-1 positive cells 12h (P <; 0.05), 24h (P <; 0.01) and 48h
      (P <; 0.05) after the surgery and showed a lower MIF tautomerase activity 12h (P
      <; 0.01), 24h (P <; 0.01) and 48h (P <; 0.01) after the surgery. Moreover, EFS
      significantly decreased the mRNA levels of IL-beta (P <; 0.05) and MMP-9 at 48h
      (P <; 0.01) after the injury. CONCLUSIONS: EFS could attenuate secondary
      inflammatory response of injured spinal cord shortly after SCI, and EFS treatment
      could be a candidate for SCI therapy.

PMID- 29060278
TI  - A study on setting of the fatigue limit of temporary dental implants.
AB  - A temporary dental implant is a medical device which is temporarily used to
      support a prosthesis such as an artificial tooth used for restoring patient's
      masticatory function during implant treatment. It is implanted in the oral cavity
      to substitute for the role of tooth. Due to the aging and westernization of
      current Korean society, the number of tooth extraction and implantation
      procedures is increasing, leading to an increase in the use and development of
      temporary dental implants. Because an implant performs a masticatory function in
      place of a tooth, a dynamic load is repeatedly put on the implant. Thus, the
      fatigue of implants is reported to be the most common causes of the fracture
      thereof. According to the investigation and analysis of the current domestic and
      international standards, the standard for fatigue of implant fixtures is not
      separately specified. Although a test method for measuring the fatigue is
      suggested in an ISO standard, it is a standard for permanent dental implants.
      Most of the test standards for Korean manufacturers and importers apply 250 N or
      more based on the guidance for the safety and performance evaluation of dental
      implants. Therefore, this study is intended to figure out the fatigue standard
      which can be applied to temporary dental implants when measuring the fatigue
      according to the test method suggested in the permanent dental implant standard.
      The results determined that suitable fatigue standards of temporary dental
      implants should be provided by each manufacturer rather than applying 250 N. This
      study will be useful for the establishment of the fatigue standards and fatigue
      test methods of the manufacturers and importers of temporary dental implants.

PMID- 29060279
TI  - A wireless batteryless implantable radiofrequency lesioning device powered by
      intermediate-range segmented coil transmitter.
AB  - A batteryless implantable radiofrequency lesioning (RFL) device powered by
      magnetic coupling is presented. The implant is composed of bipolar RFL
      electrodes, an energy-receiving coil, and a resonant capacitor circuit for
      maximizing the received power and providing an appropriate voltage for the
      electrodes. A 40-cm transmitting coil designed to wrap around the patient's body
      is used to generate a uniform magnetic field in a large volume so precise coil
      alignment is not necessary. The transmitting coil is divided to 24 segments by
      resonant capacitors to significantly reduce the excitation voltage to a safe
      level. The system was tested using ex-vivo chicken muscle tissue. Experimental
      results show that with a transmitting coil excitation of 1.2 Arms, the implant
      can lesion the muscle tissue by achieving a temperature of 55  degrees C. When
      the excitation increased to 1.6 Arms, the tissue temperature was increased to 83 
      degrees C. FEA simulation results demonstrate that the human body SAR is lower
      than the safety limit of 2 W kg-1 suggested by international guidelines when the
      excitation is 1.6 Arms.

PMID- 29060280
TI  - An IC-based controllable stimulator for respiratory muscle stimulation
      investigations.
AB  - Functional Electrical Stimulation can be used to restore motor functions loss
      consecutive to spinal cord injury, such as respiratory deficiency due to
      paralysis of ventilatory muscles. This paper presents a fully configurable IC
      centered stimulator designed to investigate muscle stimulation paradigms. It
      provides 8 current stimulation channels with high-voltage compliance and real
      time operation capabilities, to enable a wide range of FES applications. The
      stimulator can be used in a standalone mode, or within a closed-loop setup.
      Primary in vivo results show successful drive of respiratory muscles stimulation
      using a computer-based dedicated controller.

PMID- 29060281
TI  - An intracardiac electrogram model to bridge virtual hearts and implantable
      cardiac devices.
AB  - Virtual heart models have been proposed to enhance the safety of implantable
      cardiac devices through closed loop validation. To communicate with a virtual
      heart, devices have been driven by cardiac signals at specific sites. As a
      result, only the action potentials of these sites are sensed. However, the real
      device implanted in the heart will sense a complex combination of near and far
      field extracellular potential signals. Therefore many device functions, such as
      blanking periods and refractory periods, are designed to handle these unexpected
      signals. To represent these signals, we develop an intracardiac electrogram
      (IEGM) model as an interface between the virtual heart and the device. The model
      can capture not only the local excitation but also far-field signals and pacing
      afterpotentials. Moreover, the sensing controller can specify unipolar or bipolar
      electrogram (EGM) sensing configurations and introduce various oversensing and
      undersensing modes. The simulation results show that the model is able to
      reproduce clinically observed sensing problems, which significantly extends the
      capabilities of the virtual heart model in the context of device validation.

PMID- 29060282
TI  - A wireless optical power system for medical implants using low power near-IR
      laser.
AB  - An alternative method of transcutaneous wireless optical energy supply to an
      artificial cardiac pacemaker has been conceived, thereby negating the possibility
      of electromagnetic interference. In this research, a comparative analysis is made
      between two distinct arrays of photovoltaic cells, consisting of two different
      geometries. Being powered by a 5 mW 750 nm laser, that has a different spot size
      for each topology; both models are tested by their ability to charge a 150 mAh
      rechargeable LiPo battery, while being embedded underneath a layer of skin
      tissue. This system in turn, regulates the power supplied to a low power medical
      implant (<; 10 mW), in the place of conventional batteries. For a charging period
      of 60 minutes, results indicate that a pacemaker utilizing this system can
      sustain operation for nearly 85 hours, without any noticeable side-effects or
      changes in temperature.

PMID- 29060283
TI  - Deep scattering convolution network based features for ultrasonic fatty liver
      tissue characterization.
AB  - Accumulation of excess fat in the liver tissue is the leading cause for
      dysfunction of liver, which can lead to the diseases from fibrosis to end stage
      cirrhosis. Hence, early detection of fatty liver becomes crucial in avoiding the
      liver from permanent failure. Depending on the concentration of fat in the
      tissue, the liver is classified as Normal, Grade 1, Grade 2 and Grade 3
      respectively. The texture of liver tissue in ultrasound image is so specific to
      the concentration of fat, hence classifying the fatty liver is formulated as a
      texture discrimination problem. In this paper, we present an automated algorithm
      for grading the tissue of a fatty liver based on the features obtained from the
      invariant scattering convolution network (ISCN). ISCN, which involves cascade of
      modulus complex wavelet transforms and averaging operations results in scattering
      coefficients (SC), these coefficients will give stable invariant representations
      and also maps the texture of fatty liver image to a discriminative manifold
      giving good features for classification. SC are of high dimension and hence a
      compact representation feature is obtained by summing all the SC coefficients.
      Summed SC features along with cubic SVM classifier gave an accuracy of 96.6% in
      automatically categorizing the fatty content present in the tissue of a liver.

PMID- 29060284
TI  - NucleiNet: A convolutional encoder-decoder network for bio-image denoising.
AB  - Generic and scalable data analysis procedures are highly demanded by the
      increasing number of multi-dimensional biomedical data. However, especially for
      time-lapse biological data, the high level of noise prevents for automated high
      throughput analysis methods. The rapid developing of machine-learning methods and
      particularly deep-learning methods provide new tools and methodologies that can
      help in the denoising of such data. Using a convolutional encoder-decoder
      network, one can provide a scalable bio-image platform, called NucleiNet, to
      automatically segment, classify and track cell nuclei. The proposed method can
      achieve 0.99 F-score and 0.99 pixel-wise accuracy on C. elegans dataset, which
      means that over 99% of nuclei can be successfully detected with no merging nuclei
      found.

PMID- 29060285
TI  - Automated discrimination of dementia spectrum disorders using extreme learning
      machine and structural T1 MRI features.
AB  - The classification of neuroimaging data for the diagnosis of Alzheimer's Disease
      (AD) is one of the main research goals of the neuroscience and clinical fields.
      In this study, we performed extreme learning machine (ELM) classifier to
      discriminate the AD, mild cognitive impairment (MCI) from normal control (NC). We
      compared the performance of ELM with that of a linear kernel support vector
      machine (SVM) for 718 structural MRI images from Alzheimer's Disease Neuroimaging
      Initiative (ADNI) database. The data consisted of normal control, MCI converter
      (MCI-C), MCI non-converter (MCI-NC), and AD. We employed SVM-based recursive
      feature elimination (RFE-SVM) algorithm to find the optimal subset of features.
      In this study, we found that the RFE-SVM feature selection approach in
      combination with ELM shows the superior classification accuracy to that of linear
      kernel SVM for structural T1 MRI data.

PMID- 29060287
TI  - Brain tumor segmentation using cascaded deep convolutional neural network.
AB  - Gliomas are the most common and threatening brain tumors with little to no
      survival rate. Accurate detection of such tumors is crucial for survival of the
      subject. Naturally, tumors have irregular shape and can be spatially located
      anywhere in the brain, which makes it a challenging task to segment them
      accurately enough for clinical purposes. In this paper, an automated segmentation
      algorithm for brain tumor using deep convolutional neural networks (DCNN) is
      proposed. Deep networks tend to have a lot of parameters thus over-fitting is
      almost always an issue especially when data are sparse. Max-out and drop-out
      layers are used to reduce the chances of over-fitting since data are scant. Patch
      based training method is used for the model where two types of patches sized
      37*37 and 19*19 with same center pixel are selected. The proposed algorithm
      includes preprocessing in which images are normalized and bias field corrected,
      and post processing where small false positives are removed using morphological
      operators. BRATS 2013 dataset is used for evaluation of the proposed method,
      where it outperforms state-of-the-art methods with similar settings in key
      performance indicators.

PMID- 29060286
TI  - Exploring transfer learning for gastrointestinal bleeding detection on small-size
      imbalanced endoscopy images.
AB  - The success of Convolutional Neural Network (CNN) is attributed to their ability
      to learn rich midlevel image representations as opposed to hand-crafted low-level
      features used in many natural image classification methods. Learning CNN,
      however, amounts to estimating millions of parameters and requires a very large
      number of annotated image samples. In this paper, we explored transfer learning
      for gastrointestinal bleeding detection on small-size imbalanced endoscopy
      images, and showed how image representations learned with CNN on large-scale
      annotated datasets can be efficiently transferred to other tasks with limited
      amount of training data. We first transferred pre-trained Inception V3 model
      trained on the ImageNet dataset to compute mid-level image representation, and
      then fine-tuned the trained model with labeled endoscopy images, and resumed
      training from already learned weights. Additionally, we introduce both data
      augmentation and image resampling to increase the size of the training database
      and the positive sample rate to perform the Transfer Learning. Our results showed
      that our transfer learning method produces the best performance on AUC (the area
      under the receiver operating curve), Precision, Recall and Accuracy as compared
      to both the hand-crafted feature based method and training CNN model from-scratch
      method.

PMID- 29060288
TI  - Surgical tool detection in cataract surgery videos through multi-image fusion
      inside a convolutional neural network.
AB  - The automatic detection of surgical tools in surgery videos is a promising
      solution for surgical workflow analysis. It paves the way to various
      applications, including surgical workflow optimization, surgical skill evaluation
      and real-time warning generation. A solution based on convolutional neural
      networks (CNNs) is proposed in this paper. Unlike existing solutions, the
      proposed CNN does not analyze images independently. it analyzes sequences of
      consecutive images. Features extracted from each image by the CNN are fused
      inside the network using the optical flow. For improved performance, this multi
      image fusion strategy is also applied while training the CNN. The proposed
      framework was evaluated in a dataset of 30 cataract surgery videos (6 hours of
      videos). Ten tool categories were defined by surgeons. The proposed system was
      able to detect each of these categories with a high area under the ROC curve
      (0.953 <= Az <= 0.987). The proposed detector, based on multi-image fusion, was
      significantly more sensitive and specific than a similar system analyzing images
      independently (p = 2.98 * 10-6 and p = 2.07 * 10-3, respectively).

PMID- 29060289
TI  - Screening patients for risk of sleep apnea using facial photographs.
AB  - We investigated using frontal and profile facial photographic images for
      screening patients for risk of sleep apnea. A 180 image pairs were used from
      patients who were diagnosed using an attended overnight polysomnogram test into
      controls (AHI<;10/h) and sleep apnea (AHI>=10/h). A series of 35 landmarks and 71
      features motivated by craniofacial structure pertinent to upper airway physiology
      were identified on the photographs. After reducing the dimension of the feature
      set using recursive feature selection, the features were processed by a Support
      Vector Machine (SVM). Classification was performed using linear kernel SVM. The
      accuracy and area under Receiver Operating Curve (ROC) improved when the number
      of features reduced from 71 to eight top-ranked features. Further improvement was
      achieved by adding clinical measurements to the selected features resulting in
      the accuracy of 80% and the area under ROC of 0.83.

PMID- 29060290
TI  - Automatic quiet sleep detection based on multifractality in preterm neonates:
      Effects of maturation.
AB  - This study investigates the multifractal formalism framework for quiet sleep
      detection in preterm babies. EEG recordings from 25 healthy preterm infants were
      used in order to evaluate the performance of multifractal measures for the
      detection of quiet sleep. Results indicate that multifractal analysis based on
      wavelet leaders is able to identify quiet sleep epochs, but the classifier
      performances seem to be highly affected by the infant's age. In particular, from
      the developed classifiers, the lowest area under the curve (AUC) has been
      obtained for EEG recordings at very young age (<= 31 weeks post-menstrual age),
      and the maximum at full-term age (>= 37 weeks post-menstrual age). The
      improvement in classification performances can be due to a change in the
      multifractality properties of neonatal EEG during the maturation of the infant,
      which makes the EEG sleep stages more distinguishable.

PMID- 29060291
TI  - Mutual information for intrapartum fetal heart rate analysis.
AB  - The analysis of the temporal dynamics in intrapartum fetal heart rate (FHR),
      aiming at early detection of fetal acidosis, constitutes an intricate signal
      processing task, that continuously receives significant research efforts. Entropy
      and entropy rates, envisaged as measures of complexity, often computed via
      popular implementations referred to as Approximate Entropy (ApEn) or Sample
      Entropy (SampEn), have regularly been reported as significant features for
      intrapartum FHR analysis. The present contribution aims to show how mutual
      information enhances characterization of FHR temporal dynamics and improves fetal
      acidosis detection performance. To that end, mutual information is first
      connected to ApEn and SampEn both conceptually and with respect to estimation
      procedure. Second, mutual information, ApEn and SampEn are computed on a large (?
      1000 subjects) and documented database of FHR data, collected in a French
      academic hospital. Reported results show that the use of mutual information
      permits to significantly outperform ApEn and SampEn for acidosis detection,
      during any stage of labor.

PMID- 29060292
TI  - Portable neonatal EEG monitoring and sonification on an Android device.
AB  - Clinical evaluation of electroencephalogram (EEG) is important for understanding
      and monitoring the electrical activity present in the brain. In collusion with
      engineering advances, the movement towards portable, rapid and low-cost EEG
      monitoring is growing. This will allow a greater availability of monitoring
      technologies for assessing brain function and health in disadvantaged
      communities. This paper presents an alternative method for interpreting neonatal
      brain health in real-time via the sonification of EEG on a smartphone. The paper
      discusses the implementation of the real-time EEG sonification using a phase
      vocoder and shows how the method is achievable using low-cost smartphone
      technologies with energy efficient algorithms.

PMID- 29060293
TI  - A semi-Markov chain approach to modeling respiratory patterns prior to extubation
      in preterm infants.
AB  - After birth, extremely preterm infants often require specialized respiratory
      management in the form of invasive mechanical ventilation (IMV). Protracted IMV
      is associated with detrimental outcomes and morbidities. Premature extubation, on
      the other hand, would necessitate reintubation which is risky, technically
      challenging and could further lead to lung injury or disease. We present an
      approach to modeling respiratory patterns of infants who succeeded extubation and
      those who required reintubation which relies on Markov models. We compare the use
      of traditional Markov chains to semi-Markov models which emphasize cross-pattern
      transitions and timing information, and to multi-chain Markov models which can
      concisely represent non-stationarity in respiratory behavior over time. The
      models we developed expose specific, unique similarities as well as vital
      differences between the two populations.

PMID- 29060295
TI  - Convolutional neural networks for event-related potential detection: impact of
      the architecture.
AB  - The detection of brain responses at the single-trial level in the
      electroencephalogram (EEG) such as event-related potentials (ERPs) is a difficult
      problem that requires different processing steps to extract relevant discriminant
      features. While most of the signal and classification techniques for the
      detection of brain responses are based on linear algebra, different pattern
      recognition techniques such as convolutional neural network (CNN), as a type of
      deep learning technique, have shown some interests as they are able to process
      the signal after limited pre-processing. In this study, we propose to investigate
      the performance of CNNs in relation of their architecture and in relation to how
      they are evaluated: a single system for each subject, or a system for all the
      subjects. More particularly, we want to address the change of performance that
      can be observed between specifying a neural network to a subject, or by
      considering a neural network for a group of subjects, taking advantage of a
      larger number of trials from different subjects. The results support the
      conclusion that a convolutional neural network trained on different subjects can
      lead to an AUC above 0.9 by using an appropriate architecture using spatial
      filtering and shift invariant layers.

PMID- 29060294
TI  - Influence of ECG sampling rate in fetal heart rate variability analysis.
AB  - Fetal hypoxia results in a fetal blood acidosis (pH<;7.10). In such a situation,
      the fetus develops several adaptation mechanisms regulated by the autonomic
      nervous system. Many studies demonstrated significant changes in heart rate
      variability in hypoxic fetuses. So, fetal heart rate variability analysis could
      be of precious help for fetal hypoxia prediction. Commonly used fetal heart rate
      variability analysis methods have been shown to be sensitive to the ECG signal
      sampling rate. Indeed, a low sampling rate could induce variability in the heart
      beat detection which will alter the heart rate variability estimation. In this
      paper, we introduce an original fetal heart rate variability analysis method. We
      hypothesize that this method will be less sensitive to ECG sampling frequency
      changes than common heart rate variability analysis methods. We then compared the
      results of this new heart rate variability analysis method with two different
      sampling frequencies (250-1000 Hz).

PMID- 29060296
TI  - Design of deep convolutional networks for prediction of image rapid serial visual
      presentation events.
AB  - We report in this paper an investigation of convolutional neural network (CNN)
      models for target prediction in time-locked image rapid serial visual
      presentation (RSVP) experiment. We investigated CNN models with 11 different
      designs of convolution filters in capturing spatial and temporal correlations in
      EEG data. We showed that for both within-subject and cross-subject predictions,
      the CNN models outperform the state-of-the-art algorithms: Bayesian linear
      discriminant analysis (BLDA) and xDAWN spatial filtering and achieved >6%
      improvement. Among the 11 different CNN models, the global spatial filter and our
      proposed region of interest (ROI) achieved best performance. We also implemented
      the deconvolution network to show how we can visualize from activated hidden
      units for target/nontarget events learned by the ROI-CNN. Our study suggests that
      deep learning is a powerful tool for RSVP target prediction and the proposed
      model is applicable for general EEG-based classifications in brain computer
      interaction research. The code of this project is available at
      https://github.com/ZijingMao/ROICNN.

PMID- 29060297
TI  - A novel approach for automatic detection of Atrial Fibrillation based on Inter
      Beat Intervals and Support Vector Machine.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with a
      major economic burden for the society. Automatic detection of AF in long term
      recordings can efficiently assist in early diagnosis and management of
      comorbidities associated with AF. This study presents a novel approach for AF
      detection based on Inter Beat Intervals (IBI) extracted from long term
      electrocardiogram (ECG) recordings. Five time-domain features are extracted from
      the IBIs and a Support Vector Machine (SVM) is used for classification. The
      results are compared to a state of the art algorithm based on raw ECG. Both
      algorithms are evaluated on the MIT-BIH Atrial Fibrillation database resulting in
      equally high classification performance (Sensitivity >= 95%). The proposed
      approach requires detection of R-peaks in the ECG signal but allows for
      significantly reduced computation time without loss of performance.

PMID- 29060298
TI  - Informative sensor selection and learning for prediction of lower limb kinematics
      using generative stochastic neural networks.
AB  - We propose a novel approach of selecting useful input sensors as well as learning
      a mathematical model for predicting lower limb joint kinematics. We applied a
      feature selection method based on the mutual information called the variational
      information maximization, which has been reported as the state-of-the-art work
      among information based feature selection methods. The main difficulty in
      applying the method is estimating reliable probability density of input and
      output data, especially when the data are high dimensional and real-valued. We
      addressed this problem by applying a generative stochastic neural network called
      the restricted Boltzmann machine, through which we could perform sampling based
      probability estimation. The mutual informations between inputs and outputs are
      evaluated in each backward sensor elimination step, and the least informative
      sensor is removed with its network connections. The entire network is fine-tuned
      by maximizing conditional likelihood in each step. Experimental results are shown
      for 4 healthy subjects walking with various speeds, recording 64 sensor
      measurements including electromyogram, acceleration, and foot-pressure sensors
      attached on both lower limbs for predicting hip and knee joint angles. For test
      set of walking with arbitrary speed, our results show that our suggested method
      can select informative sensors while maintaining a good prediction accuracy.

PMID- 29060299
TI  - Using non-iterative methods and random weight networks to classify upper-limb
      movements through sEMG signals.
AB  - This paper presents the use of two non-iterative methods to perform the
      classification of 17 different upper-limb movements through sEMG signal
      processing. The two methods were compared with a SVM classifier using three
      different databases involving amputee subjects. The non-iterative methods
      presented equivalent or superior classification accuracy than SVM method.
      Thereafter a stage of PCA pre-processing method was used in order to promote a
      better class separation prior the non-iterative classifiers. The best accuracy
      result without PCA was achieved by the Regularized Extreme Learning Machines
      algorithm (88,4% for non-amputee subjects and 79,4% for the amputee). The PCA
      method used boosted the accuracy of the two non-iterative methods which the mean
      accuracy was 94% for the non-amputee subjects and 85% for the amputee subjects.

PMID- 29060300
TI  - Exploration and validation of alternate sensing methods for wearable continuous
      pulse transit time measurement using optical and bioimpedance modalities.
AB  - In this work we explore the viability of a multimodal sensing device that can be
      integrated in a wearable form factor for daily, non-invasive ambulatory blood
      pressure (BP) monitoring. A common approach in previous research has been to rely
      on measuring the pulse transit time (PTT), which has been shown to be correlated
      with the BP. In this work, we look into the feasibility of measuring PTT using
      sensors separated by a small distance on one arm so that any eventual realization
      of the system is convenient to wear and use over long periods of time. Moreover,
      we investigate the combined use of two different modalities for cardiovascular
      measurement: the optical photoplethysmogram (PPG) as well as the bio-potential
      based impedance (Bio-Z) measurement. These two modalities have been previously
      only studied on their own or in conjunction with the electrocardiogram (ECG) for
      the purpose of estimating PTT. We measure the PTT from the wrist to the finger
      using Bio-Z and PPG sensors, and compare it to the conventional PTT measured from
      the ECG to PPG at the finger, in order to prove that it can be an effective
      replacement for existing PTT measurement strategies. Moreover, successful
      measurement of PTT with two different modalities of sensors at close proximity
      will allow designs with multiple heterogeneous sensors on a more versatile
      wearable sensing platform that is optimized for power and is more robust to
      environmental or skin contact changes. This will enable the next generation of
      smart watches that capture PTT and BP. Experiments were conducted in vivo with
      simultaneous ECG, Bio-Z and PPG sensors, and results indicate that the PTT
      calculated from the Bio-Z and PPG sensors placed at a close distance correlates
      well with the more established PTT measurement using the ECG in conjunction with
      PPG, with correlation coefficient as high as 0.92.

PMID- 29060301
TI  - In vitro cell culture study of the conditions of inhibition effect of tumors
      under alternating electric field.
AB  - In vitro cell culture device was developed for the investigation of inhibition
      effect of cell colonies using alternating electric field. Cancer cells were
      cultured in 3D hydrogel and cell colonies, or called tumor spheroids, were
      gradually formed in the culture device. During the culture course, alternating
      electric field was applied and the conditions were investigated to optimize the
      inhibition effect of cell colonies. Results showed that electric field at
      frequency of 130 kHz and 0.5 Vpp was the minimal effective conditions of the
      inhibition of cell colonies. The device was demonstrated to provide a practical
      tool for the investigation of the efficacy and the therapeutic conditions of
      inhibiting tumors.

PMID- 29060302
TI  - Evaluation of histological and biomechanical properties on engineered meniscus
      tissues using sonication decellularization.
AB  - Sonication decellularization treatment requires proper evaluations on its ability
      to decellularize meniscus tissue efficiently. This study was done to evaluate the
      histological and biomechanical properties within meniscus scaffolds. Van Gieson
      staining was done to evaluate the efficiency of cell removal in meniscus tissues.
      The consequences of treatment on viscoelastic properties are vital for scaffolds
      quality and were properly investigated. Picrosirius red and Safranin-O/Fast green
      staining was carried out to detect extracellular matrix materials (ECM).
      Sonication decellularization treatment has the ability to demonstrated complete
      nuclei removal compare to control samples as well as maintaining viscoelastic
      properties, namely stiffness, compression and residual force. Thus, sonication
      decellularization treatment had successfully produced and prepared a meniscus
      bioscaffold candidate in which its biomechanical strength is sustained through
      protection of ECM properties.

PMID- 29060303
TI  - Improve blood compatibility of bioresorbable magnesium stents coated with
      functionalized anti-CD34 antibody and heparin-collagen multiplayers.
AB  - Instentrestenosis and late stent thrombosis continue to be the greatest
      limitations of drug-eluting stents. In this study, an anti-CD34 antibody
      functionalized multilayer of heparin/collagen type I is developed by layer-by
      layer assemble to enhance biocompatibility and recruit endothelial progenitor
      cells. The SEM results demonstrate that (Hep/Col)5-coated samples have a rougher
      surface compared to (Hep/Col)2-coated samples and untreated samples. The EDX and
      FTIR results both confirmed the presence of heparin and collagen onto the
      modified samples. The immunofluorescence staining outcomes demonstrated that anti
      CD34 antibody has successfully immobilized onto modified Mg discs.

PMID- 29060304
TI  - Evaluation of recellularization on decellularized aorta scaffolds engineered by
      ultrasonication treatment.
AB  - Aortic scaffolds prepared using sonication decellularization treatment has
      provided a successful medium for repopulation with vascular smooth muscle cells
      (VSMCs). The objective of this study is to explore the potential of tissue
      decellularization using ultrasonication treatment and its recellularization
      before implantation of the cell-seeded scaffolds into host. Aorta tissue samples
      are decellularized in 2% SDS with sonication for 10 hours and compared with the
      native tissues. The 4',6-diamidino-2-phenylindole (DAPI) staining was used to
      evaluate the decellularization and Hematoxylin-Eosin (H-E) staining was used to
      compare the VSMCs infiltrations onto the decellularized tissues at day-0 and day
      6 after cell-seeding. The results histologically showed complete DNA removal from
      scaffolds after decellularization and subsequent recellularization resulted in
      successful VSMCs infiltration. Accordingly, the decellularized tissues treated
      with 2% SDS in sonication demonstrated successful VSMCs repopulation afterward
      and is speculated to have less toxicity and able to be effectively implanted into
      host.

PMID- 29060305
TI  - A three-dimensional cell culture device for simulation of hepatic hypertension.
AB  - Hepatic stellate cells (HSCs) play a crucial role in the development of liver
      fibrosis which is characterized by massive tissue scarring, elevated hepatic
      sinusoidal pressure, and portal hypertension. However, while a multitude of
      chemical factors have been investigated in the pathogenesis of liver fibrosis,
      physical factors such as elevated hydrostatic pressure and shear stress caused by
      blood flow in sinusoids remain unclear. In this study, we developed a three
      dimensional (3D) cell culture microfluidic platform that mimics the physical
      environments of hepatic sinusoids to investigate the effects of elevated
      hydrostatic pressure on HSCs phenotypes.

PMID- 29060306
TI  - Phase-based SSVEPs for real-time control of a motorised bed.
AB  - Brain-computer interface (BCI) systems have emerged as an augmentative technology
      that can provide a promising solution for individuals with motor dysfunctions and
      for the elderly who are experiencing muscle weakness. Steady-state visually
      evoked potentials (SSVEPs) are widely adopted in BCI systems due to their high
      speed and accuracy when compared to other BCI paradigms. In this paper, we apply
      combined magnitude and phase features for class discrimination in a real-time
      SSVEP-based BCI platform. In the proposed real-time system users gain control of
      a motorised bed system with seven motion commands and an idle state. Experimental
      results amongst eight participants demonstrate that the proposed real-time BCI
      system can successfully discriminate between different SSVEP signals achieving
      high information transfer rates (ITR) of 82.73 bits/min. The attractive features
      of the proposed system include noninvasive recording, simple electrode
      configuration, excellent BCI response and minimal training requirements.

PMID- 29060307
TI  - Hierarchical decoding of grasping commands from EEG.
AB  - Brain-Computer Interfaces may present an intuitive way for motor impaired end
      users to operate assistive devices of daily life. Recent studies showed that
      complex kinematics like grasping can be successfully decoded from low frequency
      electroencephalogram. In this work we present a hierarchical method to
      asynchronously discriminate two different grasps often used in daily life actions
      (palmar, pincer) from a combined set of motor execution and motor intention. We
      compared sensorimotor rhythms based features and time features from the low
      frequency spectrum for best discrimination results. Our results show not only the
      principle feasibility of the proposed method with detection of asynchronous motor
      intention at rates of 80% accuracy and subsequent grasping discrimination over
      60%, but also that low frequency time domain features provide a more consistent
      detection pattern. Although the basis of this results is still an off-line
      analysis we are confident that these results can be transferred to on-line use.

PMID- 29060308
TI  - Detection of self-paced movement intention from pre-movement electroencephalogram
      signals with Hilbert transform.
AB  - The movement related cortical potential (MRCP) is a well-known neural signature
      of human's self-paced movement intention, which can be exploited by future
      neuroprosthesis. Most existing studies have explored the amplitude representation
      for the movement intention. In this paper we investigate the Hilbert transformed
      MRCP, which implicitly includes phase information complementarily to amplitude
      information, for the detection of self-paced upper-limb movement intention. On
      the datasets in which 5 healthy subjects executed a self-initiated upper limb
      center-out reaching task in three sessions, we have evaluated the detection model
      with Hilbert transformed MRCP as features and the state-of-art one with the
      original MRCP amplitude as features. Results show that the Hilbert transformed
      MRCP based detector is more accurate than the original MRCP based one.

PMID- 29060309
TI  - The contribution of different frequency bands in class separability of covert
      speech tasks for BCIs.
AB  - Several recent studies demonstrate the possibility of using user initiated covert
      speech mental tasks in brain computer interfaces with varying degrees of success,
      but details of the best frequency features had not been investigated. In this
      work, ten volunteers in the age range of 22-70 years participated in the
      experiment. Eight of them were neurologically healthy, one user was dyslexic, and
      another was autistic. The four words "back", "forward", "left", and "right" were
      shortened into "BA", "FO", "LE", and "RY", which are phonetically dissimilar and
      cognitively relevant directional commands. Participants were asked to covertly
      speak each as soon as the letters appeared on a screen. Volunteers completed five
      recording runs. During each run the four words were presented in random
      succession to avoid sequence bias. The recorded EEG data from the ten users were
      analysed to discover the best features within a Gabor Transform of the signals,
      i.e., those yielding the highest word-pair classification accuracy for this
      specific type of linguistic mental activity. Using this BCI, suitable class
      separability of covert speech tasks is confirmed for all, including disabled
      users, with consistently high classification accuracy from 72% to 88% in all
      cases. Like motor imagery tasks, Alpha and Beta band activity were found to
      contain 12% and 31% of the most important features respectively. Gamma band
      activity, which indicates high mental functions, contains 57% of the most
      important features in this study.

PMID- 29060310
TI  - EEG classification for motor imagery BCI using phase-only features extracted by
      independent component analysis.
AB  - The accurate classification of the electroencephalography (EEG) signals is the
      most important task towards the development of a reliable motor imagery brain
      computer interface (MI-BCI) system. In this study, we utilized a publically
      available BCI Competition-IV 2008 dataset IIa. This study address to the binary
      classification problem of the motor imagery EEG data by using a sigmoid
      activation function-based extreme learning machines (ELM). We proposed a novel
      method of extracting the features from the EEG signals by first applying the
      independent component analysis (ICA) on the time series data and transforming the
      ICA time series data into Fourier domain and then extract the phase information
      from the Fourier spectrum. This phase information was further used to calculate
      the maximized cross-correlation connectivity matrix. The upper diagonal of this
      matrix was then vectorized and it serves as the basic feature for the ELM
      classification framework. By using the phase-only features we achieved 97.80% (p
      <; 0.0022) nested cross-validated classification accuracy. In addition, this
      process is relatively computationally inexpensive. Thus, it can be an excellent
      candidate for the motor imagery BCI applications.

PMID- 29060311
TI  - Speeding up SVM training in brain-computer interfaces.
AB  - Traditional Support Vector Machine (SVM) is widely used classification method for
      brain-computer interface (BCI). However, SVM has a high computational complexity.
      In this paper, Gaussian Mixture Model (GMM)-based training data reduction is
      proposed to reduce high computational complexity. The proposed method is
      configured as follows: First, wavelet-based combined feature vectors are applied
      for motor imagery electroencephalography (EEG) identification and principal
      component analysis (PCA) are used to reduce the dimension of feature vectors.
      Thereafter, the GMM is implemented to reduce training data sizes. Finally, a
      nonlinear SVM classifier is used to classify the reduced training data. The
      performance of the proposed method was evaluated using three different motor
      imagery datasets in terms of accuracy and training time. The results from the
      study indicate that the proposed method achieves high accuracy with faster
      computational time in motor imagery EEG classification.

PMID- 29060312
TI  - Predicting the stimulation effectiveness using pre-stimulation neural states via
      optogenetic activation of the medial septum glutamatergic neurons modulating the
      hippocampal neural activity.
AB  - In this study, we explored the role of pre-stimulation neural states on the
      effectiveness of optogenetic stimulation. Optogenetic stimulation was applied to
      the medial septum glutamatergic neurons to modulate the hippocampal neural
      activity in a rat tetanus toxin seizure model. The hippocampal local field
      potential was recorded using a multi electrode array in an awake and behaving
      rat. Optical stimulation with a 465nm light source was applied at 35Hz in a 20
      seconds off / 20 seconds on pattern with simultaneous recording from the
      hippocampus. Both the baseline and the stimulation period recordings were divided
      into 2 second segments and used for the further analysis. In the first
      experiment, a support vector machine (SVM) model classified the neural states by
      using spectral features between 0 and 50Hz. 447 out of 545 segments (82.02%) were
      correctly labeled as 'Baseline' while only 326 out of 544 (59.93%) segments from
      the stimulation period were correctly labeled as 'Stimulation.' As the ratio of
      mislabels is significantly higher for the stimulation period (chi-squared,
      p<;0.01), we concluded that the stimulation was not always effective. In the
      second experiment, an SVM model predicted the stimulation effectiveness using the
      spectral features of the pre-stimulation segments. The classification result
      shows that 63.7% of the pre-stimulation segments correctly predicted the
      stimulation effectiveness. These findings suggest that the prediction of the
      stimulation effectiveness may improve the stimulation efficacy by implementing a
      state-based stimulation protocol.

PMID- 29060313
TI  - Galvanic Vestibular Stimulation (GVS) effects on impaired interhemispheric
      connectivity in Parkinson's Disease.
AB  - Disrupted interhemispheric connectivity (IHC) is being increasingly recognized as
      a robust feature of a number of neurological diseases, including Parkinson's
      Disease (PD). We investigated whether or not Galvanic Vestibular Stimulation
      (GVS) - a proposed treatment for PD - affected IHC in 11 PD subjects (off
      medication). In order to avoid the confound of stimulation artifact disrupting
      the EEG, we investigated the immediate period (52 sec) after stimulation (72 sec)
      with noisy 1/f-type GVS stimuli. Partial Least Squares (PLS) regression was used
      to determine the subject-specific linear combination of EEG electrodes that
      maximized covariance between hemispheres and then computed coherence between the
      dominant PLS components. PD subjects had increased IHC <;~10 Hz and decreased IHC
      >13 Hz compared to 11 healthy, age-matched controls. After GVS in PD subjects, a
      significant increase in IHC was detected, especially above 30 Hz. We suggest that
      GVS may partially exert its beneficial effects in PD by "normalizing" impaired
      IHC.

PMID- 29060314
TI  - Network-mediated responses of ON ganglion cells to electric stimulation become
      less consistent across trials during retinal degeneration.
AB  - Microelectronic retinal prostheses are being developed to restore sight in
      individuals blinded by outer retinal degenerative diseases such as retinitis
      pigmentosa and age-related macular degeneration. Unfortunately, the quality of
      vision restored by these devices is still limited. To improve the quality of
      elicited vision, our group studies the responses of retinal neurons to electric
      stimulation. Our previous work showed that responses mediated through the retinal
      network are reproducible with high temporal precision, even for spikes that occur
      >100 ms after stimulus onset. Because they arise through the network, it is
      important to understand whether such reliability changes in the degenerate
      retina. Here, we examined response variability at several different stages of
      degeneration: postnatal day 14 (P14), P18, P31 and P60 in a well-established
      mouse model of degeneration (rd10). Spiking responses of ON alpha RGCs were
      recorded multiple times to an identical electric stimulus. We found that the
      trial-to-trial variability increased over the course of retinal degeneration.
      This finding may help to explain the reported variability in the quality of
      elicited vision across subjects using these devices.

PMID- 29060315
TI  - An artifact-suppressed stimulator for simultaneous neural recording and
      stimulation systems.
AB  - This paper proposes an artifact-suppressed stimulator with a referenced and tuned
      push-pull stimulation (RTPPS) scheme where a tri-polar electrode is employed. The
      stimulation pulses delivered to two working electrodes are complementary and thus
      one counteracts with the other to suppress the artifact at the recording site.
      The prototype stimulator chip is implemented in 0.18-MUm CMOS process technology.
      In-vivo experiments are carried out with the chip to demonstrate the proposed
      artifact-suppression technique in a simultaneous neural recording and stimulation
      system. The results show that the stimulation artifact can be greatly reduced.
      The amplitude of the measured stimulation artifact is therefore constrained in a
      negligible level (10%-20%) compared to recorded neural spikes.

PMID- 29060316
TI  - A machine learning approach to characterizing the effect of asynchronous
      distributed electrical stimulation on hippocampal neural dynamics in vivo.
AB  - Asynchronous distributed microelectrode theta stimulation (ADMETS) of the
      hippocampus has been shown to reduce seizure frequency in the tetanus toxin rat
      model of mesial temporal lobe epilepsy suggesting a hypothesis that ADMETS
      induces a seizure resistant state. Here we present a machine learning approach to
      characterize the nature of neural state changes induced by distributed
      stimulation. We applied the stimulation to two animals under sham and ADMETS
      conditions and used a combination of machine learning techniques on intra
      hippocampal recordings of Local Field Potentials (LFPs) to characterize the
      difference in the neural state between sham and ADMETS. By iteratively fitting a
      logistic regression with data from the inter-stimulation interval under sham and
      ADMETS condition we found that the classification performance improves for both
      animals until 90s post stimulation before leveling out at AUC of 0.64 +/- 0.2 and
      0.67 +/- 0.02 when all inter-stimulation data is included. The models for each
      animal were re-fit using elastic net regularization to force many of the model
      coefficients to 0, identifying those that do not optimally contribute to the
      classifier performance. We found that there is significant variation in the non
      zero coefficients between animals (p <; 0.01), suggesting that the ADMETS induced
      state is represented differently between subject. These findings lay the
      foundation for using machine learning to robustly and quantitatively characterize
      neural state.

PMID- 29060317
TI  - Effects of transcranial direct current stimulation on steady-state visual evoked
      potentials.
AB  - Recently, transcranial direct current stimulation (tDCS) has attracted increasing
      attention in the field of neuro-modulation because of its capacity to modulate
      cortical excitability noninvasively. Previous findings have demonstrated its
      effectiveness in visual studies. However, few studies have referred to steady
      state visual evoked potential (SSVEP), a promising visual evoked potential that
      has been widely used in brain-computer interfaces. The present work investigated
      the effects of tDCS on SSVEPs. Sham and 1 mA real tDCS (anodal and cathodal) in a
      PO7-PO8 montage were administered for 15 min in 12 healthy subjects. Compared
      with sham conditions, both anodal and cathodal tDCS significantly decreased 7-Hz
      SSVEP power. Also, anodal tDCS increased 10-Hz SSVEP power. Our study
      demonstrated that tDCS over occipital areas altered brain activity evoked by
      visual stimuli.

PMID- 29060318
TI  - A novel Blood Pressure estimation method combing Pulse Wave Transit Time model
      and neural network model.
AB  - Blood Pressure (BP) measurement can assist doctors to assess patients'
      cardiovascular status and diagnose heart diseases. Pulse Wave Transit Time (PWTT)
      model is one frequently used BP estimation method to monitor BP continuously in
      clinics. However, individual variations may influence the measurement accuracy of
      PWTT model. Focusing on above promble, this paper proposes a novel BP estimation
      method combining a classical PWTT model and a neural network model. The novel
      method is composed of five steps: signal pre-processing, feature extraction,
      initial PWTT model selection, model correction by neural network model, and final
      PWTT model identification. A validation experiment based on 10 patients from
      Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) database showed
      that the BP estimation results by our method had a minimum mean of error readout
      value 5 mmHg with a standard deviation of error readout value +/-8mmHg. As a
      result, both the diastolic blood pressure and systolic blood pressure estimation
      by our method can meet clinical requirements.

PMID- 29060319
TI  - Elastic modulus estimation based on local displacement observation of elastic
      body.
AB  - A method is proposed that provides estimates of the spatial variation of elastic
      moduli using local displacements of the elastic body. A central issue of
      elastography imaging has been the limited area of measurement. With the proposed
      method, stiffness parameter estimations are considered as minimization problems
      using finite-element models. The sparseness of the gradient of tissue elasticity
      is also exploited to improve estimation accuracy. Simulation experiments show
      that based on a 5% area of observation of a simple plate model with non-uniform
      elasticity the spatial variation of Young's modulus is reconstructed to within 5%
      accuracy. This result suggests that the proposed framework significantly extends
      the area of estimation overcoming the limitations of conventional elastography
      techniques.

PMID- 29060320
TI  - The classification for "equilibrium triad" sensory loss based on sEMG signals of
      calf muscles.
AB  - Surface Electromyography (sEMG) has been commonly applied for analysing the
      electrical activities of skeletal muscles. The sensory system of maintaining
      posture balance includes vision, proprioception and vestibular senses. In this
      work, an attempt is made to classify whether the body is missing one of the sense
      during balance control by using sEMG signals. A trial of combination with
      different features and muscles is also developed. The results demonstrate that
      the classification accuracy between vision loss and the normal condition is
      higher than the one between vestibular sense loss and normal condition. When
      using different features and muscles, the impact on classification results is
      also different. The outcomes of this study could aid the development of sEMG
      based classification for the function of sensory systems during human balance
      movement.

PMID- 29060321
TI  - Likelihood-based artefact detection in continuously-acquired patient vital signs.
AB  - Robust continuous monitoring of patient vital signs (VS) is limited by
      artefactual data yielding measurements that are not representative of the
      patient's physiology. These artefacts are typified by several distinct
      "archetypes". We present several of these archetypal artefacts for heart rate
      (HR) monitoring, and propose a light weight, real-time algorithm to remove the
      majority of these artefacts. Most artefacts are not identifiable by their values
      in absolute terms, but instead by their values relative to other measurements
      nearby in time. We model temporally-proximate measurements as independent and
      identically distributed (i.i.d.) samples from a Gamma distribution. Measurements
      with low likelihood with respect to the distribution are candidates for artefact
      removal. This lightweight algorithm is important for real-time deployment on
      wearable sensors, which are becoming increasingly common in hospital and home
      care. The clinical applicability of artefact-removal is demonstrated in its
      ability to enhance patient deterioration detection. A Kalman filter-based patient
      monitoring algorithm is shown to improve early warning of deterioration when the
      proposed artefact-removal algorithm is used. We demonstrate this real-time system
      with patient data from a clinical trial that we have undertaken.

PMID- 29060322
TI  - Accuracy of a wavelet-based fall detection approach using an accelerometer and a
      barometric pressure sensor.
AB  - GOAL: Falls are a major source of morbidity in older adults, and 50% of older
      adults who fall cannot rise independently after falling. Wearable sensor-based
      fall detection devices may assist in preventing long lies after falls. The goal
      of this study was to determine the accuracy of a novel wavelet-based approach to
      automatically detect falls based on accelerometer and barometric pressure sensor
      data. METHODS: Participants (n=15) mimicked a range of falls, near falls, and
      activities of daily living (ADLs) while wearing accelerometer and barometric
      pressure sensors on the lower back, chest, wrists and thighs. The wavelet
      transform using pattern adapted wavelets was applied to detect falls from the
      sensor data. RESULTS: In total, 525 trials (194 falls, 105 near-falls and 226
      ADLs) were included in our analysis. When we applied the wavelet-based method on
      only accelerometer data, classification accuracies ranged from 82% to 96%, with
      the chest sensor providing the highest accuracy. Accuracy improved by 3.4% on
      average (p=0.041; SD=3.0%) when we also included the barometric pressure sensor
      data. The highest classification accuracies (of 98%) were achieved when we
      combined wavelet-based features and traditional statistical features in a
      multiphase fall detection model using machine learning. CONCLUSION: We show that
      the wavelet-based approach accurately distinguishes falls from near-falls and
      ADLs, and that it can be applied on wearable sensor data generated from various
      body locations. Additionally, we show that the accuracy of a wavelet-based fall
      detection system can be further improved by combining accelerometer and
      barometric pressure sensor data, and by incorporating wavelet and statistical
      features in a machine learning classification algorithm.

PMID- 29060323
TI  - Arterial blood pressure estimation using ultrasound: Clinical results on healthy
      volunteers and a medicated hypertensive volunteer.
AB  - This study presents a non-occlusive and non-invasive ultrasound-based technique
      to measure blood pressure. Most popular clinically-used arterial blood pressure
      measurement techniques suffer from important weaknesses including being
      inaccurate, invasive, or occlusive. In the proposed technique, an ultrasound
      probe is placed on the patient's carotid artery and the contact force between the
      probe and the tissue is slowly increased while ultrasound images and contact
      force data are recorded. From this data, the artery is segmented and the
      segmentation data is sent into an optimization procedure; after post-processing,
      blood pressure is displayed to the user. This technique was applied to 24 healthy
      single-visit volunteers, one multi-visit healthy volunteer, and one multi-visit
      medicated hypertensive volunteer. Compared to the oscillometric cuff, the
      accuracy and precision of the algorithm-reported systolic pressure is -2.4 +/-
      10.2 mmHg, and for diastolic pressure is -0.3 +/- 8.2 mmHg. This method has the
      potential to occupy a clinical middle-ground between the arterial catheter and
      the oscillometric cuff.

PMID- 29060324
TI  - Transmit coil design for Wireless Power Transfer for medical implants.
AB  - A new design approach for the design of transmit coils for Wireless Power
      Transfer (WPT) is presented. The theoretical formulation involves a figure of
      merit that has to be maximized to solve for the surface current. Numerical
      predictions and comparisons with practical measurements for the coil parameters
      (inductance. resistance) underscore the success of this approach in terms of
      achieving strong coupling with a receive coil while maintaining low resistance.

PMID- 29060325
TI  - A comparison of two anatomical body models derived from the female visible human
      project data.
AB  - Two electromagnetic human body models independently developed from the same image
      dataset-the voxel-based AustinWoman and surface-based VHP-Female models- are
      compared. In addition to contrasting volumes and crosssection images of their
      tissues, the power absorbed by the two models under plane-wave excitation is also
      compared. Five different numerical methods are used to compute the absorbed power
      and to evaluate modeling and computational errors.

PMID- 29060326
TI  - Measurement of perception thresholds for electrical noise stimuli.
AB  - In previous research, the application of sub-threshold electrical nerve
      stimulation (SENS) to peripheral nerves has been shown to improve tactile
      sensitivity. SENS has applications in the symptomatic treatment of a wide array
      of conditions that result in the loss of peripheral nerve function. These include
      diabetes, stroke, and age related peripheral neuropathy. The technology is
      dependent on careful control of the amplitude of the intervention stimulation
      relative to the user's perception threshold. However, little is known about the
      factors that influence the perception threshold and whether it can be treated as
      a constant. Here we present a study where we applied a two alternate forced
      choice paradigm to determine electrical perception threshold. We investigated
      participant, noise frequency characteristics, electrode location, electrode type,
      and electrode impedance characteristics as explanatory factors for the
      variability seen in the threshold outcome. We find that the electrical perception
      threshold is dependent on the frequency characteristics of the signal applied,
      but varies widely without correlation to the remaining variables. It was also
      highly variable when re-tested under identical conditions. Our results cast doubt
      on the ability to treat the electrical threshold as a single value that holds
      constant for a particular participant and electrode placement. This finding has
      significant implications in SENS applications.

PMID- 29060327
TI  - New conducted electrical weapons: Finite element modeling of safety margins.
AB  - Introduction-We have previously published on the ventricular fibrillation (VF)
      risk with TASER(r) X26 conducted electrical weapon (CEW). Our risk model
      accounted for realistic body mass index distributions, modeled the effects of
      partial or oblique dart penetration, and used epidemiological CEW statistics. As
      new CEWs have become available to law enforcement, their cardiac safety profile
      was not quantified. Therefore, we applied our VF probability model to evaluate
      their cardiac risk. Methods and Results-An eXperimental Rotating-Field (XRF)
      waveform CEW and the X2 CEW are new 2-shot electrical weapon models designed to
      target a precise amount of delivered charge per pulse, 64 MUC and 62 MUC,
      respectively. They can deploy 1 or 2 probe pairs, delivered by 2 separate
      cartridges. New Smart Probes (SP), which carry 11.5 mm long CEW darts, can be
      used with XRF and X2 CEWs. Finite element modeling (FEM) was used to approximate
      the current and charge densities produced by XRF and X2 CEWs in tissues located
      in the vicinity of darts, including accounting for the effects of fat,
      anisotropic skeletal muscles, sternum, ribs, and lungs. Using our previous
      cardiac risk probabilistic model, the new XRF and X2 CEWs operated with 11.5 mm
      SPs, had an estimated overall theoretical VF risk of less than 1 in 1 300 000 and
      1 in 1 490 000 cases, respectively. We also found that the XRF and X2 CEWs had
      increased cardiac safety margins with respect to those previously reported for
      the X26 CEWs when all three CEW models were operated with 9 mm CEW darts. Lastly,
      the cardiac risk of these new CEWs (<; 0.76 ppm) was found to be much lower than
      reported levels of CEW non-cardiac fatal injuries (e.g. falls and burns, > 7.2
      ppm). Conclusions-While not risk-free, the new TASER XRF and X2 CEWs offer
      increased cardiac safety margins and extremely low cardiac risk profiles.

PMID- 29060328
TI  - System design and experimental research of lower esophageal sphincter stimulator
      for treatment of gastroesophageal reflux disease.
AB  - Electrical stimulation therapy (EST) of lower esophageal sphincters (LES) is a
      new technique for the treatment of gastroesophageal reflux disease (GERD). In
      this paper, an implantable LES stimulator with wireless power transmission is
      proposed for the treatment of GERD. The LES stimulator is composed of an
      implantable pulse generator (IPG), an external controller, and a wireless power
      transmission module. The IPG, whose area is 31*21 mm2, is designed to generate
      voltage-regulated constant-current stimulation pulses. The external controller
      allows for wireless programming of the IPG via a Bluetooth Low Energy (BLE)
      module. The wireless power transmission module provides power for the IPG.
      According to the measurement of output stimulus waveforms, the proposed LES
      stimulator is capable of delivering electrical stimulations with a current
      ranging between 0 and 8 mA. To evaluate the safety and efficacy of the proposed
      LES stimulator, experiments were performed on 12 male New Zealand white rabbits.
      Esophageal manometry was performed before and after the procedure and the LES
      pressure (LESP) has been recorded. The mean LESP is increased significantly in
      the stimulation group than the sham group (stimulation group: 9.25+/-1.24 mmHg vs
      13.99 +/-1.28 mmHg, p<;0.05; sham group: 9.00+/-1.22 mmHg vs 9.23+/-1.27 mmHg,
      p=0.267). The results show that the electrical stimulation delivered by the LES
      stimulator can safely and effectively increase resting LES pressure in acute
      animal models, suggesting that the implantable LES stimulator is a perspective
      approach for treating GERD in clinics.

PMID- 29060329
TI  - Design and application of a novel gastric pacemaker.
AB  - Omnipresent bioelectrical events known as slow waves are responsible for
      coordinating motility in the gastrointestinal tract. Functional motility
      diseases, such as gastroparesis, are associated with slow wave dysrhythmias.
      Electrical stimulation is a potential therapy to correct abnormal slow wave
      patterns. We present the design and application of a new gastric pacemaker. Real
      time changes to the stimulation parameters such as period, amplitude and pulse
      width were applied using a graphical user interface, which communicated with the
      microcontroller to deliver the stimulus. The new pacemaker allows the voltage,
      delivered current and resistance between pacing electrodes to be continuously
      monitored. The pacing device was applied experimentally and was able to modulate
      and entrain gastric slow wave activity. After the onset of pacing, the direction
      of slow wave propagation was altered. Furthermore, the mean velocity and
      amplitude of slow wave activity increased from 4.7+/-1.5 to 5.4+/-1.3 mm/s, and
      from 1.1+/-1.1 to 1.7+/-0.9 mV, respectively. A simplified bidomain electrical
      model was used to simulate the recorded stimulus artifact. The model illustrated
      a new approach to evaluate if the stimulus has been delivered to the gastric
      tissue. The new pacing device and model will be used to investigate the
      mechanisms that allow pacing to entrain slow wave activity.

PMID- 29060330
TI  - New conducted electrical weapons: Electrical safety relative to relevant
      standards.
AB  - INTRODUCTION: We have previously published about TASER(r) conducted electrical
      weapons (CEW) compliance with international standards. CEWs deliver electrical
      pulses that can inhibit a person's neuromuscular control or temporarily
      incapacitate. An eXperimental Rotating-Field (XRF) waveform CEW and the X2 CEW
      are new 2-shot electrical weapon models designed to target a precise amount of
      delivered charge per pulse. They both can deploy 1 or 2 dart pairs, delivered by
      2 separate cartridges. Additionally, the XRF controls delivery of incapacitating
      pulses over 4 field vectors, in a rotating sequence. As in our previous study, we
      were motivated by the need to understand the cardiac safety profile of these new
      CEWs. The goal of this paper is to analyze the nominal electrical outputs of
      TASER XRF and X2 CEWs in reference to provisions of all relevant international
      standards that specify safety requirements for electrical medical devices and
      electrical fences. Although these standards do not specifically mention CEWs,
      they are the closest electrical safety standards and hence give very relevant
      guidance. METHODS: The outputs of several TASER XRF and X2 CEWs were measured
      under normal operating conditions. The measurements were compared against
      manufacturer specifications. CEWs electrical output parameters were reviewed
      against relevant safety requirements of UL 69, IEC 60335-2-76 Ed 2.1, IEC 60479
      1, IEC 60479-2, AS/NZS 60479.1, AS/NZS 60479.2, IEC 60601-1 and BS EN 60601-1.
      RESULTS AND CONCLUSION: Our study confirmed that the nominal electrical outputs
      of TASER XRF and X2 CEWs lie within safety bounds specified by relevant
      standards.

PMID- 29060331
TI  - New conducted electrical weapons: Thoracic cage shielding effects.
AB  - INTRODUCTION: The TASER(r) conducted electrical weapon (CEW) delivers electrical
      pulses that can temporarily incapacitate subjects. For existing CEW models, we
      have previously presented the distribution of currents in tissues posterior to
      the sternum and their likelihood of triggering cardiac arrhythmias. New models,
      the eXperimental Rotating-Field (XRF) waveform CEW (in development) and the X2
      CEW (released) have not been investigated. Both the XRF and X2 CEWs target a
      precise amount of delivered charge per pulse, 64 MUC and 62 MUC, respectively.
      The goal of this study was to numerically model the thoracic cage attenuation of
      currents and electric fields delivered by the new CEWs and to find whether the
      heart is shielded from the induction of any dangerous arrhythmias. METHODS AND
      RESULTS: Finite element modeling (FEM) was used to approximate the current
      density and electric field strength in tissues around the thoracic cage. FEM
      boundary conditions were set to correspond to output waveforms of the new CEWs,
      the XRF and the X2. We analyzed a CEW dart deployment scenario that had both
      darts located over the anterior aspect of the sternum. We found that the sternum
      and thoracic cage provided significant attenuation of currents and electrical
      fields. CONCLUSION: The sternum and the thoracic cage significantly attenuated
      currents and electric fields delivered by XRF and X2 CEWs. These tissues
      'shielded' the heart against potentially dangerous cardiac arrhythmias. The
      shorter durations and reduced amount of charged delivered by the XRF and the X2
      CEWs resulted in increased cardiac safety margins.

PMID- 29060332
TI  - Investigating fetal myocardial function in heart anomalies by Doppler myocardial
      performance indices.
AB  - Fetal myocardial performance index are used to assess aspects of systolic and
      diastolic function in developing fetal heart. The aim of this study was to
      determine normal values of fetal left ventricular (LV) Tei Index (TI) for
      measuring systolic performance and K-Index (KI) for diastolic performance in
      early (<;32 weeks), Mid (32-35 weeks) and late trimester (35-41 weeks) normal
      fetuses and fetuses with congenital heart diseases (CHD). Simultaneous recordings
      of Doppler Ultrasound Signal (DUS) of the LV outflow tracts and fetal
      electrocardiogram signals were obtained in 57 normal and 14 fetuses with CHD.
      CHDs were categorized in two types (conduction pathway abnormalities [8 cases]
      and structural anomalies [6 cases]). The LV isovolumic contraction time (ICT),
      isovolumic relaxation time (IRT), ventricular ejection time (VET) and ventricular
      filling time (VFT) were measured from amplitudes and peaks of high frequency
      component of DUS signals by an automated model. The TI and the new index were
      calculated by using the formula (ICT + IRT)/VET and (ICT + IRT)/VFT respectively.
      The TI did not show any significant change from CHD (conduction) to CHD
      (structural) fetuses (0.72+/- 0.09 vs 0.76+/-0.02; NS). On the other hand, KI
      showed significant decline in values (0.82+/-0.24 vs 0.49+/-0.34; p<;0.05) during
      normal development period and CHD with structural anomalies particularly. The
      correlation of KI with gestational ages was found to be negative and significant
      (r=- 0.29; p=0.025). Both TI and KI can be easily obtained in the fetus from DUS
      recording without the need for precise anatomic imaging. In conclusion, KI may be
      a useful tool to explore the healthy development of fetal myocardial function and
      identify fetuses with CHD (structural). More research is needed to check if KI
      could recognize the compromised fetuses from normal ones in future.

PMID- 29060333
TI  - Detecting fetal heart sounds by means of Fractal Dimension analysis in the
      Wavelet domain.
AB  - Phonocardiography is a low-cost technique for the detection of fetal heart sounds
      (FHS) that can extend clinical auscultation in mobile and home care setups. The
      work presented here examines the transferability of a Wavelet Transform (WT)
      based method that combines also Fractal Dimension (FD) analysis, previously
      proposed as WT-FD for the cases of lung and bowel sound analysis [4], to the
      extraction of FHSs. The WT-FD method has been evaluated with 12 simulated FHS
      signals and has shown promising results in terms of accuracy and performance
      (89%) in identifying the location of heartbeat, even in cases of signals with
      additive noise up to (6dB). This robustness paves the way for WT-FD testing in
      real FHSs, recorded under clinical setting, clearly contributing to better
      evaluation of the fetal heart functionality.

PMID- 29060334
TI  - Self-reported well-being score modelling and prediction: Proof-of-concept of an
      approach based on linear dynamic systems.
AB  - Assessment and recognition of perceived well-being has wide applications in the
      development of assistive healthcare systems for people with physical and mental
      disorders. In practical data collection, these systems need to be less intrusive,
      and respect users' autonomy and willingness as much as possible. As a result,
      self-reported data are not necessarily available at all times. Conventional
      classifiers, which usually require feature vectors of a prefixed dimension, are
      not well suited for this problem. To address the issue of non-uniformly sampled
      measurements, in this study we propose a method for the modelling and prediction
      of self-reported well-being scores based on a linear dynamic system. Within the
      model, we formulate different features as observations, making predictions even
      in the presence of inconsistent and irregular data. We evaluate the proposed
      method with synthetic data, as well as real data from two patients diagnosed with
      cancer. In the latter, self-reported scores from three well-being-related scales
      were collected over a period of approximately 60 days. Prompted each day, the
      patients had the choice whether to respond or not. Results show that the proposed
      model is able to track and predict the patients' perceived well-being dynamics
      despite the irregularly sampled data.

PMID- 29060335
TI  - Removal of spurious phase variations in oscillatory signals.
AB  - The study of oscillatory electroencephalogram (EEG) data has been one of the main
      sources for the analysis of different brain functions and decoding a variety of
      cognitive processes. One of the interesting features that has been the focus of
      study in the last decades is the study of instantaneous phase information in EEG.
      Phase synchronization techniques are among the main analysis tools that measure
      the degree of phase re-organization in signals. In phase re-organization
      approach, the phase alignment in stimulus induced potentials has been shown to be
      informative for decoding cognitive processes. Despite the developments in this
      area, the precision of measures may vary based on the level of noise. Phase
      distortion due to artefacts and a variety of pre-processing steps that are
      applied on data, can introduce artificial phase alignment. These artificial phase
      variations (that is referred to spurious phase variations) are not correlated to
      any stimulus or event. In a new study, it has been showed that a low
      instantaneous envelope lead to abrupt changes in IP, which could distort the
      results of phase synchronization. In this work, we propose a method that is able
      to estimate the true phase based on the measurements and estimate a standard
      deviation for the computed phase. The method enables to remove the effect of
      artificial phase changes due to low envelope. In this approach the analytic
      signal is modeled by a Kalman smoother, and estimates a more reliable version of
      the IP from the measurements. At last, we evaluate the model on different
      synthetic data sets.

PMID- 29060336
TI  - Spatial projection as a preprocessing step for EEG source reconstruction using
      spatiotemporal Kalman filtering.
AB  - The reconstruction of brain sources from non-invasive electroencephalography
      (EEG) or magnetoencephalography (MEG) via source imaging can be distorted by
      information redundancy in case of high-resolution recordings. Dimensionality
      reduction approaches such as spatial projection may be used to alleviate this
      problem. In this proof-of-principle paper we apply spatial projection to solve
      the problem of information redundancy in case of source reconstruction via
      spatiotemporal Kalman filtering (STKF), which is based on state-space modeling.
      We compare two approaches for incorporating spatial projection into the STKF
      algorithm and select the best approach based on its performance in source
      localization with respect to accurate estimation of source location, lack of
      spurious sources, computational speed and small number of required optimization
      steps in state-space model parameter estimation. We use state-of-the-art
      simulated EEG data based on neuronal population models, for which the number and
      location of sources is known, to validate the source reconstruction results of
      the STKF. The incorporation of spatial projection into the STKF algorithm solved
      the problem of information redundancy, resulting in correct source localization
      with no spurious sources, and decreased the overall computational time in STKF
      analysis. The results help make STKF analyses of high-density EEG, MEG or
      simultaneous MEG-EEG data more feasible.

PMID- 29060337
TI  - Source reconstruction via the spatiotemporal Kalman filter and LORETA from EEG
      time series with 32 or fewer electrodes.
AB  - The clinical routine of non-invasive electroencephalography (EEG) is usually
      performed with 8-40 electrodes, especially in long-term monitoring, infants or
      emergency care. There is a need in clinical and scientific brain imaging to
      develop inverse solution methods that can reconstruct brain sources from these
      low-density EEG recordings. In this proof-of-principle paper we investigate the
      performance of the spatiotemporal Kalman filter (STKF) in EEG source
      reconstruction with 9-, 19- and 32- electrodes. We used simulated EEG data of
      epileptic spikes generated from lateral frontal and lateral temporal brain
      sources using state-of-the-art neuronal population models. For validation of
      source reconstruction, we compared STKF results to the location of the simulated
      source and to the results of low-resolution brain electromagnetic tomography
      (LORETA) standard inverse solution. STKF consistently showed less localization
      bias compared to LORETA, especially when the number of electrodes was decreased.
      The results encourage further research into the application of the STKF in source
      reconstruction of brain activity from low-density EEG recordings.

PMID- 29060338
TI  - Detecting dynamical changes in vital signs using switching Kalman filter.
AB  - Vital signs contain valuable information about patients' health status during
      their stay in general wards, when the deterioration process begins. The use of
      methods to predict and detect regime changes such as switching models can help to
      understand how vital sign dynamics are altered in disease conditions. However,
      time series of vital signs are remarkably non-stationary in these scenarios. The
      objective of this study is to quantify the potential bias of switching models in
      the presence of non-stationarities, when the inputs are spectral, symbolic and
      entropy indices. To distinguish stationary from non-stationary periods, a test
      was used to verify the stability of the mean and variance over short periods.
      Then, we compared the results from a switching Kalman filter (SKF) model trained
      using indices obtained over stationary periods with a model trained solely over
      non-stationary periods. It was observed that indices measured over stationary and
      non-stationary periods were significantly different. The results of switching
      models were highly dependent on the indices that were used as inputs. The multi
      scale entropy (MSE) approach presented the highest correlation values between non
      stationary and stationary switches, an average correlation coefficient of 38%.

PMID- 29060339
TI  - An extended Kalman filter with inequality constraints for real-time detection of
      intradialytic hypotension.
AB  - Intradialytic hypotension (IDH) is the most common complication of hemodialysis,
      affecting 15-50% of all dialysis sessions. Previously, we had presented a non
      invasive Polyvinylidene Fluoride (PVDF) based sensor in the form of a ring to
      measure vascular tone and we showed that the morphology of the signal can be
      utilized to predict IDH. This paper presents an approach for analyzing the PVDF
      signal using extended Kalman filter (EKF) and a synthetic model that has
      previously been used to model the ECG signal with Gaussian functions. Moreover, a
      novel approach for incorporating state inequality constraints into the EKF
      process using a gradient projection method is introduced. The taut string
      algorithm was first used to estimate the outline of the signal and remove it to
      highlight the reflection waves. Then, the EKF was used to characterize the
      morphology of the signal using Gaussian functions. The amplitudes of the Gaussian
      functions were used as features to train a classifier. The results indicated that
      the PPV and NPV for the prediction were 83.33% and 100%, respectively.

PMID- 29060340
TI  - EEG-based emotion estimation using adaptive tracking of discriminative frequency
      components.
AB  - EEG-based emotion recognition has received increasing attention in the past few
      decades. The frequency components that give effective discrimination between
      different emotion states are subject specific. Identification of these subject
      specific discriminative frequency components (DFCs) is important for the accurate
      classification of emotional activities. This paper investigated the potential of
      adaptive tracking of DFCs as an effective method for choosing the discriminative
      bands of EEG patterns and improving emotion recognition performance. 13 healthy
      volunteers were emotionally elicited by pictures selected from the International
      Affective Picture System (IAPS). Discriminative frequency components were tracked
      and analyzed for each subject and classification of three emotions (pleasant/high
      arousal, neutral, unpleasant/high arousal) was performed by employing a Hidden
      Markov Model (HMM) and a Support Vector Machine (SVM). Our results showed that
      adaptive tracking of DFCs improved classification accuracies significantly and
      the highest average accuracy of 82.85% was achieved by SVM.

PMID- 29060341
TI  - A template subtraction method for the removal of cardiogenic oscillations on
      esophageal pressure signals.
AB  - Esophageal pressure (Pes) is usually measured in patients receiving mechanical
      ventilation and is used for the assessment of lung mechanics. However, its
      interpretation is complicated by the presence of cardiogenic oscillations (CGO).
      In this article we present a novel method for the reduction of CGO based on the
      identification of pressure templates. Similar approaches are known for the
      removal of electrocardiographic (ECG) artifacts from the electromyogram (EMG).
      The proposed method is tested on clinical recordings of patients under assisted
      spontaneous ventilation. Besides the improvement of the respiratory signals, the
      identified CGO templates can be used diagnostically when viewed in relation to
      corresponding ECG data. This approach is illustrated on a few sample datasets.

PMID- 29060342
TI  - FPGA implementation of adaptive beamforming in hearing aids.
AB  - Beamforming is a spatial filtering technique used in hearing aids to improve
      target sound reception by reducing interference from other directions. In this
      paper we propose improvements in an existing architecture present for two
      omnidirectional microphone array based adaptive beamforming for hearing aid
      applications and implement the same on Xilinx Artix 7 FPGA using VHDL coding and
      Xilinx Vivado(r) 2015.2. The nulls are introduced in particular directions by
      combination of two fixed polar patterns. This combination can be adaptively
      controlled to steer the null in the direction of noise. The beamform patterns and
      improvements in SNR values obtained from experiments in a conference room
      environment are analyzed.

PMID- 29060343
TI  - Detection of user independent single trial ERPs in Brain Computer Interfaces: An
      adaptive spatial filtering approach.
AB  - Brain Computer Interfaces (BCIs) use brain signals to communicate with the
      external world. The main challenges to address are speed, accuracy and
      adaptability. Here, a novel algorithm for P300 based BCI spelling system is
      presented, specifically suited for single-trial detection of Event-Related
      Potentials (ERPs) by combining spatial filtering and new feature extraction
      methods. The adaptive spatial filtering technique, axDAWN, removes the need for
      calibration of the system thereby improving the overall speed of the system.
      Besides, axDAWN enhances the P300 response to target stimuli. The wavelet
      decomposition and entropy of the recorded ERPs are shown to be correlated with
      the presence of the P300 responses. The proposed scheme is validated thoroughly
      in a P300 speller and provides a solution to achieve high accuracy results for
      single-trial detection of ERPs, being the system user independent.

PMID- 29060344
TI  - Low-latency VLSI architecture for neural cross-frequency coupling analysis.
AB  - Growing evidence suggests that cross-frequency coupling (CFC) is a key mechanism
      in neuronal computation, communication, and learning in the brain. Abnormal CFC
      has been implicated in pathological brain states such as epilepsy and Parkinson's
      disease. A reduction in excessive coupling has been shown in effective
      neuromodulation treatments, suggesting that CFC may be a useful feedback measure
      in closed-loop neural stimulation devices. However, processing latency limits the
      responsiveness of such systems. A VLSI architecture is presented which implements
      three selectable measures of CFC to enable the application specific trade-off
      between low-latency and high-accuracy processing. The architecture is
      demonstrated using in-vitro human neocortical slice recordings, with a latency of
      48ms.

PMID- 29060345
TI  - Neuronal desynchronization as marker of an impaired brain network.
AB  - Synchronization is a central key feature of neural information processing and
      communication between different brain areas. Disturbance of oscillatory brain
      rhythms and decreased synchronization have been associated with different
      disorders including schizophrenia. The aim of this study was to investigate
      whether synchronization (in relaxed conditions with no stimuli) between different
      brain areas within the delta, theta, alpha (alpha1, alpha2), beta (beta1, beta2),
      and gamma bands is altered in patients with a neurological disorder in order to
      generate significant cortical enhancements. To achieve this, we investigated
      schizophrenic patients (SZO; N=17, 37.5+/-10.4 years, 15 males) and compared them
      to healthy subjects (CON; N=21, 36.7+/-13.4 years, 15 males) applying the phase
      locking value (PLV). We found significant differences between SZO and CON in
      different brain areas of the theta, alpha1, beta2 and gamma bands. These areas
      are related to the central and parietal lobes for the theta band, the parietal
      lobe for the alpha1, the parietal and frontal for the beta2 and the frontal
      central for the gamma band. The gamma band revealed the most significant
      differences between CON and SZO. PLV were 61.7% higher on average in SZO in most
      of the clusters when compared to CON. The related brain areas are directly
      related to cognition skills which are proved to be impaired in SZO. The results
      of this study suggest that synchronization in SZO is also altered when the
      patients were not asked to perform a task that requires their cognitive skills
      (i.e., no stimuli are applied - in contrast to other findings).

PMID- 29060346
TI  - Coherence analysis of invasive blood pressure and its noninvasive indicators for
      improvement of cuffless measurement accuracy.
AB  - Cuffless technology for blood pressure (BP) measurement offers great potential
      for unobtrusive monitoring of hypertension. However, the accuracy is still a
      challenging issue probably owning to the inadequacy of existing noninvasive BP
      indicators in tracking BP changes, i.e., either the poor trackability of the
      indicators or the lack of relationship to map the indicators to BP. To figure out
      the covariation of BP-related noninvasive indicators and BP, we propose to
      analyze the coherence of intra-arterial systolic BP (SBP) and a selected group of
      noninvasive indicators, including the mostly used pulse transit time (PTT),
      photoplethysmogram intensity ratio (PIR) and RR interval (RRI) of
      electrocardiogram (ECG), in both time domain, with singular spectrum analysis
      (SSA), and frequency domain, with cross-spectral analysis. Through SSA the SBP
      and the indicators are decomposed into fast oscillations superimposed on a slow
      time-varying component. It is found that the fast variation components oscillate
      at similar frequencies for the SBP and the indicators, while that their slow
      variation components are out of phase synchronization. Cross-spectra between SBP
      and the indicators further illustrate stronger coherence correlation at high
      frequencies (HF, 0.15-0.40 Hz) (PTT: 0.54+/-0.30, PIR: 0.73+/-0.25, RRI: 0.63+/
      0.25) than at low frequencies (LF, 0.04-0.15 Hz) (PTT: 0.24+/-0.19, PIR: 0.37+/
      0.23, RRI: 0.33+/-0.23). The results suggest that the widely used indicators are
      poor to track the LF component of BP. Our study reveals the importance of
      exploring LF-related BP indicators as well as new models to integrate LF and HF
      information for improvement of cuffless BP measurement accuracy.

PMID- 29060347
TI  - Phase-amplitude coupling analysis of spontaneous EEG activity in Alzheimer's
      disease.
AB  - This study was aimed at exploring phase-amplitude coupling (PAC) patterns of
      neural activity in dementia due to Alzheimer's disease (AD). For this task, five
      minutes of spontaneous electroencephalographic (EEG) activity from 22 patients
      with mild AD and 16 cognitively healthy controls were studied. To assess PAC
      patterns, phase-locking value was computed between the phase of low frequencies
      and the power of high frequencies within each sensor. Our results showed that
      high-frequency gamma power is phase-locked to the alpha peak in EEG signals.
      Furthermore, statistically significant differences (p<;0.05, permutation test)
      between patients with mild AD and elderly controls were observed at the lower
      left temporo-parietal area, suggesting that early stages of AD elicit a region
      specific decrease of PAC in the neural activity.

PMID- 29060348
TI  - Study on the effects of brightness contrast on steady-state motion visual evoked
      potential.
AB  - Traditional steady - state visual evoked potential (SSVEP) using light flicker
      stimulation may easy cause visual fatigue with a consequent reduction of
      recognition accuracy. In the previous study, we proposed a steady - state motion
      visual evoked potential (SSMVEP) brain - computer interface (BCI) method. A black
      - white ring - shaped checkerboard was used as the visual stimulus paradigm in
      this study. The movement patterns of the checkerboard included contraction and
      expansion. Based on the signal-to-noise ratio (SNR), recognition accuracy and
      anti-fatigue properties, the effects of black-white brightness contrast on the
      brain response were investigated. Experimental results indicated that when the
      contrast ratio was the highest, it could obtain higher recognition accuracy and
      SNR, yet it was easy to cause visual fatigue. When the contrast was the lowest,
      the sensitivity of the eyes against flicker reduced to the lowest, and it could
      reduce visual fatigue. However the recognition accuracy and SNR were low. In
      contrast, the appropriate contrast could guarantee high SNR and recognition
      accuracy, and as much as possible to reduce the visual fatigue.

PMID- 29060349
TI  - Template-DTW based on inertial signals: Preliminary results for step
      characterization.
AB  - In this paper, we present a method for the creation of a library of inertial
      signals based on Dynamic Time Warping (DTW) for step characterization, with
      preliminary results in control subjects and patients with neurological diseases.
      Subjects performed a protocol including a 10 m straight walking, then turn back
      and walking for additional 10 m. The library is constructed with inertial signals
      (acceleration and angular velocities recorded in three directions) aligned with
      the DTW. Templates in the library are obtained for a specific cohort and for the
      different walking phases of the protocol. They are compared to the signal of a
      single subject by calculating a Pearson correlation coefficient. The method has
      been tested on a database of 864 exercises, obtained from 71 healthy controls, 24
      patients with Parkinson disease and 48 patients with Radiation Induced
      Leukoencephalopathy (RIL). Pearson correlation classification reports a precision
      of about 85% for step detection. For exercise characterization the sensitivity is
      about 57%, 56% and 82% for Parkinson, RIL and control subjects respectively.

PMID- 29060350
TI  - Using spatial features for classification of combined motions based on common
      spatial pattern.
AB  - Motion recognition is an important application of electromyography (EMG)
      analysis. While discrete motions such as hand open, hand close and wrist
      pronation have been extensively investigated, studies on combined motions
      involving two or more degrees of freedom (DOFs) are relatively few and the
      classification accuracy of the combined motions reported in previous studies is
      barely satisfactory. To improve the accuracy of the combined motion recognition,
      common spatial pattern (CSP) was employed in this study to extract spatial
      features. 18 forearm motion classes, consisted of 8 discrete motions and 10
      combined motions, were classified by the proposed method. Our results showed that
      the accuracy rate of CSP features was 96.3%, which outperformed the commonly used
      time-domain (TD) features by 2.4% and TD combined with auto-regression
      coefficients (TDAR) by 0.6%. Moreover, CSP features cost noticeable much less
      time than TDAR and quite less time than TD in testing. These results suggest that
      CSP features could be a better feature set for multi-DOF myoelectric control than
      conventional features.

PMID- 29060351
TI  - Surgical gesture classification using Dynamic Time Warping and affine velocity.
AB  - Minimally Invasive Surgery (MIS) has become widespread as an important surgical
      technique due to its advantages related to pain relief and short recovery time
      periods. However, this approach implies the acquisition of special surgical
      skills, which represents a challenge in the objective assessment of surgical
      gestures. In this way, several studies shown that kinematics and kinetic analysis
      of hand movement is a valuable assessment tool of basic surgical skills in MIS.
      In addition, recent researches proved that human motion performed during surgery
      can be described as a sequence of constant affine velocity movements. In this
      paper, we present a novel method to classify gestures based on an affine velocity
      analysis of 3D motion and an implementation of the Dynamic Time Warping
      algorithm. In particular, affine velocity calculation correlates kinematics and
      geometrical variables such as curvature, torsion, and euclidean velocity,
      reducing the dimension of the conventional 3D problem. In this way, using the
      simplicity of dynamic time warping algorithm allows us to perform an accurate
      classification, easier to implement and understand. Experimental validation of
      the algorithm is presented based on the position and orientation data of a
      laparoscope instrument, determiMinimally Invasive Surgery (MIS) has become
      widespread as an important surgical technique due to its advantages related to
      pain relief and short recovery time periods. However, this approach implies the
      acquisition of special surgical skills, which represents a challenge in the
      objective assessment of surgical gestures. In this way, several studies shown
      that kinematics and kinetic analysis of hand movement is a valuable assessment
      tool of basic surgical skills in MIS. In addition, recent researches proved that
      human motion performed during surgery can be described as a sequence of constant
      affine velocity movements. In this paper, we present a novel method to classify
      gestures based on an affine velocity analysis of 3D motion and an implementation
      of the Dynamic Time Warping algorithm. In particular, affine velocity calculation
      correlates kinematics and geometrical variables such as curvature, torsion, and
      euclidean velocity, reducing the dimension of the conventional 3D problem. In
      this way, using the simplicity of dynamic time warping algorithm allows us to
      perform an accurate classification, easier to implement and understand.
      Experimental validation of the algorithm is presented based on the position and
      orientation data of a laparoscope instrument, determined by six cameras. Results
      show the advantages of the proposed method compared to conventional
      Multidimensional Dynamic Time Warping to classify surgical gestures in MIS.ned by
      six cameras. Results show the advantages of the proposed method compared to
      conventional Multidimensional Dynamic Time Warping to classify surgical gestures
      in MIS.

PMID- 29060352
TI  - Biological tissues identification from their spectral signals acquired by a Raman
      needle.
AB  - In this paper, biological tissues are discriminated based on their intrinsic
      Raman spectral features. First, a Raman needle, which comprises of a Raman probe
      and a puncture needle, is devised to insert into biological tissues and acquire
      their Raman spectral data. The Savitzky-Golay filter is used to remove the data
      noise, and an adaptive iterative penalized least squares method to rectify the
      baseline. To extract the spectral features from the data, the principal component
      analysis (PCA) is used. Then, a genetic algorithm (GA) based support vector
      machine (SVM) method is proposed to classify the biological tissues based on the
      spectral features. Experimental study was conducted with different animal
      specimens and approved that the proposed methods can identify efficiently the
      different biological tissues.

PMID- 29060353
TI  - Counting malaria parasites with a two-stage EM based algorithm using crowsourced
      data.
AB  - Malaria eradication of the worldwide is currently one of the main WHO's global
      goals. In this work, we focus on the use of human-machine interaction strategies
      for low-cost fast reliable malaria diagnostic based on a crowdsourced approach.
      The addressed technical problem consists in detecting spots in images even under
      very harsh conditions when positive objects are very similar to some artifacts.
      The clicks or tags delivered by several annotators labeling an image are modeled
      as a robust finite mixture, and techniques based on the Expectation-Maximization
      (EM) algorithm are proposed for accurately counting malaria parasites on thick
      blood smears obtained by microscopic Giemsa-stained techniques. This approach
      outperforms other traditional methods as it is shown through experimentation with
      real data.

PMID- 29060354
TI  - Elastic Net based sparse feature learning and classification for Alzheimer's
      disease identification.
AB  - Magnetic resonance imaging (MRI) has been successfully applied to investigate
      neuron pathological changes. Since the high dimension of observation data, sparse
      feature learning plays an important role in overcoming the challenge of high
      variable dimension and low sample size problem among the disease identification.
      In this paper, sparse Elastic Net (EN) was used to extract low dimension features
      and to identify the Alzheimer's disease (AD). Compare with principal component
      analysis (PCA) method, the EN method can solve the problems of less samples and
      high correlations between variables. For those variables sharing the same
      biological phenomenon, it selected whole groups into the model automatically once
      one variable among them was selected. Unlike other subspace learning methods, the
      proposed method used less man-made feature setting. The problems of dimension
      reduction and classification were conducted into a similar formulation.
      Experimental results illustrated the effectiveness of the proposed method.

PMID- 29060355
TI  - Reducing false asystole alarms in intensive care.
AB  - High rates of false monitoring alarms in intensive care can desensitize staff and
      therefore pose a significant risk to patient safety. Like other critical
      arrhythmia alarms, asystole alarms require immediate attention by the care
      providers as a true asystole event can be acutely life threatening. Here, it is
      illustrated that most false asystole alarms can be attributed to poor signal
      quality, and we propose and evaluate an algorithm to identify data windows of
      poor signal quality and thereby help suppress false asystole alarms. The
      algorithm combines intuitive signal-quality features (degree of signal saturation
      and baseline wander) and information from other physiological signals that might
      be available. Algorithm training and testing was performed on the MIMIC II and
      2015 PhysioNet/Computing in Cardiology Challenge databases, respectively. The
      algorithm achieved an alarm specificity of 81.0% and sensitivity of 95.4%,
      missing only one out of 22 true asystole alarms. On a separate neonatal data set,
      the algorithm was able to reject 89.7% (890 out of 992) of false asystole alarms
      while keeping all 22 true events. The results show that the false asystole alarm
      rate can be significantly reduced through basic signal quality evaluation.

PMID- 29060356
TI  - Elimination of power line interference from ECG signals using recurrent neural
      networks.
AB  - This study proposed a method for the elimination of 50-Hz power line interference
      (PLI) in electrocardiogram (ECG) signals, using recurrent neural networks (RNN).
      The method is to preliminarily train an RNN-based model to obtain the signal
      pattern of PLI. The ECG signals are then filtered by subtracting the PLI signals
      extracted by the trained model. The results suggest that the proposed method
      could significantly relieve the distortion of QRS complex while filtering the ECG
      signals efficiently. The method was evaluated by comparing with a traditional IIR
      notch filter and an adaptive filtering method.

PMID- 29060357
TI  - A novel Heart Rate Variability analysis using Lagged Poincare plot: A study on
      hedonic visual elicitation.
AB  - This paper reports on a novel method for the analysis of Heart Rate Variability
      (HRV) through Lagged Poincare Plot (LPP) theory. Specifically a hybrid method,
      LPPsymb, including LPP quantifiers and related symbolic dynamics was proposed.
      LPP has been applied to investigate the autonomic response to pleasant and
      unpleasant pictures extracted from the International Affective Picture System
      (IAPS). IAPS pictures are standardized in terms of level of arousal, i.e. the
      intensity of the evoked emotion, and valence, i.e. the level of
      pleasantness/unpleasantness, according to the Circumplex model of Affects (CMA).
      Twenty-two healthy subjects were enrolled in the experiment, which comprised four
      sessions with increasing arousal level. Within each session valence increased
      from positive to negative. An ad-hoc pattern recognition algorithm using a Leave
      One-Subject-Out (LOSO) procedure based on a Quadratic Discriminant Classifier
      (QDC) was implemented. Our pattern recognition system was able to classify
      pleasant and unpleasant sessions with an accuracy of 71.59%. Therefore, we can
      suggest the use of the LPPsymb for emotion recognition.

PMID- 29060358
TI  - Pressure ulcer risk detection from complexity of activity.
AB  - Activity levels in nursing home residents were measured with accelerometers over
      one week as part of a multicenter randomized controlled trial, and complexity of
      the resulting activity patterns were characterized. Among 813 study participants
      on whom activity data had been collected, 16 participants developed pressure
      ulcers by the end of the study. The fractal dimension D0 of the activity series
      was lower (p=0.039) in residents who developed pressure ulcers than in controls
      matched on the basis of race, randomization group, score on the Braden scale, and
      diagnoses of cardiovascular disease and dementia. Hurst exponents indicated that
      the scaling of the power spectrum was close to 1/f in pressure ulcer cases. At
      timescales exceeding 30 minutes, approximate entropy tended to be higher in the
      controls than in the pressure ulcer cases. The fractal structure of the activity
      time series and its information content offer the ability to predict higher risk
      of development of pressure ulcers in nursing home residents.

PMID- 29060359
TI  - Feature analysis of dysphonia speech for monitoring Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that has no
      known cure and no known prevention. Early detection is crucial in order to slow
      down the progress. In the past 10 years, interest in PD analysis has visibly
      increased. Speech impairment affects the majority of people with Parkinson's
      (PWP). New features and machine learning algorithms were proposed to help
      diagnose PD and to measure a patient's progress. Using sustained vowel /a/
      recordings, we identified a more prominent set of Mel-Frequency Cepstral
      Coefficient (MFCC) and Intrinsic Mode Functions (IMF), and other parameters that
      can best represent the characteristics of Parkinson's dysphonia to assist with
      the diagnosis process. For higher quality audio signals, there is a visible
      difference in the higher MFCC coefficients, the wider spectrum bandwidth in the
      first four IMFs of PWP, and higher power intensity in the healthy subjects. We
      also found that even when the signals are downsampled into toll-quality, the
      distinguishable MFCC and IMF features were largely maintained. This enabled a
      whole possibility of providing telemedicine for PWP.

PMID- 29060360
TI  - Heart rate variability in patients with major depressive disorder and healthy
      controls during non-REM sleep and REM sleep.
AB  - The objectives of this study are to investigate heart rate variability (HRV) in
      major depressive disorder patients (MDD) and healthy controls during different
      sleep stages, and to examine the association of HRV during sleep and depression
      severity. Polysomnography was recorded from 15 depressive patients with a higher
      beck depression inventory index (BDI > 25, H-BDI-D), 15 depressive patients with
      a lower BDI index (BDI <= 25, L-BDI-D) and 15 healthy controls. HRV was
      calculated during the first three rapid eye movements (REM) periods and non-REM
      stages (i.e. sleep stage 2 and 3) with time domain, power spectral and fractal
      analysis. As a result, H-BDI-D patients showed the highest short-term fractal
      alpha-1 exponent during first REM period and healthy controls had the lowest
      values. Our results suggest an association between the depression severity and
      the autonomic nerve function, especially during the first REM sleep. The
      pathophysiological analysis for this property should be conducted in future
      prospective studies.

PMID- 29060362
TI  - Higuchi fractal dimension of the electroencephalogram as a biomarker for early
      detection of Alzheimer's disease.
AB  - It is widely accepted that early diagnosis of Alzheimer's disease (AD) makes it
      possible for patients to gain access to appropriate health care services and
      would facilitate the development of new therapies. AD starts many years before
      its clinical manifestations and a biomarker that provides a measure of changes in
      the brain in this period would be useful for early diagnosis of AD. Given the
      rapid increase in the number of older people suffering from AD, there is a need
      for an accurate, low-cost and easy to use biomarkers that could be used to detect
      AD in its early stages. Potentially, the electroencephalogram (EEG) can play a
      vital role in this but at present, no reliable EEG biomarker exists for early
      diagnosis of AD. The gradual slowing of brain activity caused by AD starts from
      the back of the brain and spreads out towards other parts. Consequently,
      determining the brain regions that are first affected by AD may be useful in its
      early diagnosis. Higuchi fractal dimension (HFD) has characteristics which make
      it suited to capturing region-specific neural changes due to AD. The aim of this
      study is to investigate the potential of HFD of the EEG as a biomarker which is
      associated with the brain region first affected by AD. Mean HFD value was
      calculated for all channels of EEG signals recorded from 52 subjects (20-AD and
      32-normal). Then, p-values were calculated between the two groups (AD and normal)
      to detect EEG channels that have a significant association with AD. k-nearest
      neighbor (KNN) algorithm was used to compute the distance between AD patients and
      normal subjects in the classification. Our results show that AD patients have
      significantly lower HFD values in the parietal areas. HFD values for channels in
      these areas were used to discriminate between AD and normal subjects with a
      sensitivity and specificity values of 100% and 80%, respectively.

PMID- 29060361
TI  - Complexity analysis of EEG under magnetic stimulation on acupoint of
      Guangming(GB37).
AB  - Changes in electroencephalogram (EEG) signals under repetitive magnetic
      stimulation at the acupoint of Guangming (GB37) were analyzed using nonlinear
      dynamics complexity. C0 complexity is a statistical indicators which can quantify
      time dynamics of EEG signals. The study compared the C0 complexity under magnetic
      stimulation at GB37 with those at a mock point, as well as the C0 complexity
      under visual stimulation before and after magnetic stimulation at GB37. The
      results showed that the C0 complexity values of EEG signals in the electrode
      F3,Cz,C4 and P3 were different depending on whether magnetic stimulation was at
      the GB37 or a mock point (P <; 0.05),and the C0 complexity of magnetic
      stimulation on GB37 was generally higher than that on mock point. Moreover, EEG
      signals from visual stimulation before magnetic stimulation at GB37 were
      significantly different from those after magnetic stimulation at GB37 in two
      electrodes which were C4 and P3(P <; 0.05). The conclusion of the study is that
      magnetic stimulation at GB37 has a significant impact on EEG signals. First, EEG
      complexity during magnetic stimulation at GB37 was significantly higher than that
      at the mock point in frontal area, central area and parietal area (electrodes F3,
      Cz, C4 and P3). Second, EEG signals in central area and parietal area (electrodes
      C4 and P3) resulting from visual stimulation differed depending on whether
      magnetic stimulation at GB37 was given. The study has important significance for
      the application of magnetic stimulation on acupoints.

PMID- 29060363
TI  - Comparison of different shielding methods in acquisition of physiological
      signals.
AB  - Power line interference in the surrounding environment could usually introduce
      many difficulties when collecting and analyzing physiological signals. Since
      power line interference is usually several orders of amplitude larger than the
      physiological electrical signals, methods of suppressing power line interference
      should be considered during the signal acquisition. Many studies used a hardware
      or software band-stop filter to suppress power line interference but it could
      easily cause attenuations and distortions to the signal of interest. In this
      study, two kinds of methods that used different signals to drive the shields of
      the electrodes were proposed to reduce the impacts of power line interference.
      Three channels of two physiological signals (ECG and EMG) were simultaneously
      collected when the electrodes were not shielded (No-Shield), shielded by ground
      signals (GND-Shield) and shielded by buffered signals of the corresponding
      electrodes (Active-Shield), respectively, on a custom hardware platform based on
      TI ADS1299. The results showed that power line interference would be
      significantly suppressed when using shielding approaches, and the Active-Shield
      method could achieve the best performance with a power line interference
      reduction up to 36dB. The study suggested that the Active-Shield method at the
      analog front-end was a great candidate to reduce power line interference in
      routine acquisitions of physiological signals.

PMID- 29060364
TI  - Investigation of Lagged Poincare Plot reliability in ultra-short synthetic and
      experimental Heart Rate Variability series.
AB  - This study reports on the reliability of Lagged Poincare Plot (LPP) parameters
      calculated from ultra-short cardiovascular time series (from 30 to 180 seconds).
      ity (HRV) signals, whereas a few studies have studied nonlinear approaches.
      Particularly, methods derived from the phase-space theory, especially the ones
      employing multi-lag analyses, are usually considered to be inaccurate with a low
      number of samples. Here we propose a comprehensive study about LPP, using both
      synthetic and real RR series. Specifically, we considered 109 5-minutes HRV
      series: 60 synthetic series generated through the Integral Pulse Frequency
      Modulation (IPFM) model and 49 experimental series acquired from healthy subjects
      during resting-state. Three parameters have been extracted through the ellipse
      fitting method, SD1, SD2 and S, using ten values of lag. All LPP parameters were
      estimated by averaging estimates gathered from segments of 30, 120 and 180
      seconds, and compared with the once from 5-minute series. Results showed
      Spearman's correlation coefficients higher than 0.9 in both synthetic and real
      series. In conclusion, SD1 gave promising results in terms of percentage absolute
      error, when it was extracted from series with a duration less than three minutes.

PMID- 29060365
TI  - Noninvasive hemoglobin measurement using unmodified smartphone camera and white
      flash.
AB  - We show that a mobile phone can measure hemoglobin levels using the built-in RGB
      camera and white LED without modification. Prior work has demonstrated that a
      smartphone using the built-in RGB camera with the aid of visible and IR lights
      can achieve a Pearson correlation results between 0.69-0.82 and an RMSE value
      between 1.26-1.56 g/dL. Our system builds upon the prior work and demonstrates
      that with only the built-in white LED, the estimation of hemoglobin level has a
      Pearson correlation of 0.62 with an RMSE of 1.27 g/dL. This extension work
      demonstrates that it is feasible to measure hemoglobin without using an IR
      source.

PMID- 29060366
TI  - Development of a portable sensorised handle for the objective assessment of the
      effectiveness and concordance of intervention plans in dementia.
AB  - Dementia is a global issue which is rising rapidly, with 46.8 million people
      worldwide living with dementia in 2015. This number is expected to increase to
      74.7 million by 2030. Some researches show that some kinds of exercises, such as
      resistance band exercises, would help to improve the memory and other abilities
      in patients with dementia. However, the true effectiveness of these activities is
      not really known due to the lack of objective assessment of efforts done during
      the long intervention time. Moreover, there is no way of measuring the actual
      activities performed by the patient without direct observation. As a consequence,
      it is impossible to measure the concordance between the patient and the
      therapist.

PMID- 29060367
TI  - Personalized cumulative UV tracking on mobiles & wearables.
AB  - Maintaining a balanced Ultra Violet (UV) exposure level is vital for a healthy
      living as the excess of UV dose can lead to critical diseases such as skin cancer
      while the absence can cause vitamin D deficiency which has recently been linked
      to onset of cardiac abnormalities. Here, we propose a personalized cumulative UV
      dose (CUVD) estimation system for smartwatch and smartphone devices having the
      following novelty factors; (a) sensor orientation invariant measurement of UV
      exposure using a bootstrap resampling technique, (b) estimation of UV exposure
      using only light intensity (lux) sensor (c) optimal UV exposure dose estimation.
      Our proposed method will eliminate the need for a dedicated UV sensor thus widen
      the user base of the proposed solution, render it unobtrusive by eliminating the
      critical requirement of orienting the device in a direction facing the sun. The
      system is implemented on android mobile platform and validated on 1200 minutes of
      lux and UV index (UVI) data collected across several days covering morning to
      evening time frames. The result shows very impressive final UVI estimation
      accuracy. We believe our proposed solution will enable the future wearable and
      smartphone users to obtain a seamless personalized UV exposure dose across a day
      paving a way for simple yet very useful recommendations such as right skin
      protective measure for reducing risk factors of long term UV exposure related
      diseases like skin cancer and, cardiac abnormality.

PMID- 29060368
TI  - A Gaussian process regression model for walking speed estimation using a head
      worn IMU.
AB  - Miniature inertial sensors mainly worn on waist, ankle and wrist have been widely
      used to measure walking speed of the individuals for lifestyle and/or health
      monitoring. Recent emergence of head-worn inertial sensors in the form of a smart
      eyewear (e.g. Recon Jet) or a smart ear-worn device (e.g. Sensixa e-AR) provides
      an opportunity to use these sensors for estimation of walking speed in real-world
      environment. This work studies the feasibility of using a head-worn inertial
      sensor for estimation of walking speed. A combination of time-domain and
      frequency-domain features of tri-axial acceleration norm signal were used in a
      Gaussian process regression model to estimate walking speed. An experimental
      evaluation was performed on 15 healthy subjects during free walking trials in an
      indoor environment. The results show that the proposed method can provide
      accuracies of better than around 10% for various walking speed regimes.
      Additionally, further evaluation of the model for long (15-minutes) outdoor
      walking trials reveals high correlation of the estimated walking speed values to
      the ones obtained from fusion of GPS with inertial sensors.

PMID- 29060369
TI  - Wearable bio signal monitoring system applied to aviation safety.
AB  - Pilots are required to have the ability to evaluate their own physical and
      psychological status to operate high performance aircrafts effectively. Existing
      studies have lacked consideration of applying bio signal of pilots in real time
      flight situation. The purpose of this study is to develop a wearable bio signal
      monitoring system that can measure the condition of pilots under an extreme
      flight environment to ensure flight safety. The wearable bio signal monitoring
      system consists of an algorithm for evaluating pilots' physiological stability,
      algorithms for detecting Gravity-induced Loss of Consciousness (G-LOC) prognosis,
      pilots' interaction module, and pilots' context awareness platform. The algorithm
      for evaluating pilots' physiological stability uses psychomotor cognitive test
      (PCT) and heart rate variability (HRV) to measure pilots' mission performance
      before flight. The algorithms for detecting G-LOC prognosis utilizes
      electromyogram (EMG) to generate warning signal during flight. The pilots'
      interaction module was developed for pilots to operate the system efficiently
      under flight environment. The pilots' context awareness platform was designed for
      the system to process multiple sensor signals in real time. This wearable bio
      signal monitoring system is expected to enhance flight safety and mission
      performance of pilots.

PMID- 29060370
TI  - A simple algorithm for emotion recognition, using physiological signals of a
      smart watch.
AB  - Recently, it has become easier and more common to measure physiological signals
      through wearable devices such as smart watches. Extracting emotional states of
      individuals with problems expressing it, such as autistic individuals, can help
      their parents, friends, and therapists to obtain a better understanding of what
      they feel throughout their day. Although emotion recognition methods based on
      physiological signals have been studied for many years, there is a smaller body
      of literature about systems working with data obtained from wearable devices. In
      this paper, we present an emotion recognition system with a small footprint
      suitable for limited resources of wearable devices. Other than identifying the
      emotions (with a success rate of 65%), The proposed system also tags each
      recognition with a confidence value (on average 57%).

PMID- 29060371
TI  - A prospective study of examining physiological signals for estimating occurrence
      of nocturnal enuresis.
AB  - The nocturnal enuresis is challenging due to the increased social activities of
      the children. This disorder significantly bothers both the children and their
      parents in psychological, behavioral, social, and financial manners. However, the
      primary treatments have limitations and further are not able to completely cure
      the disorder. In order to reduce pain and burdens of patients and their parents,
      it is important to accurately estimate when the enuretic incident occurs in
      advance. For the estimation, we have comprehensively investigated various studies
      of the nocturnal enuresis in the diverse fields. Through the investigations, we
      have summarized four hypotheses of the physiological signals related to the
      enuretic moment. In order to conquer the nocturnal enuresis, we design a
      preliminary framework sensing and investigating the physiological signals with
      the sensors. Our synthesized approach to understand and estimate the moments of
      the enuretic incidents can establish a foothold to complete the promising
      prediction system.

PMID- 29060372
TI  - Wearable Internet of Things - from human activity tracking to clinical
      integration.
AB  - Wearable devices for human activity tracking have been emerging rapidly. Most of
      them are capable of sending health statistics to smartphones, smartwatches or
      smart bands. However, they only provide the data for individual analysis and
      their data is not integrated into clinical practice. Leveraging on the Internet
      of Things (IoT), edge and cloud computing technologies, we propose an
      architecture which is capable of providing cloud based clinical services using
      human activity data. Such services could supplement the shortage of staff in
      primary healthcare centers thereby reducing the burden on healthcare service
      providers. The enormous amount of data created from such services could also be
      utilized for planning future therapies by studying recovery cycles of existing
      patients. We provide a prototype based on our architecture and discuss its
      salient features. We also provide use cases of our system in personalized and
      home based healthcare services. We propose an International Telecommunication
      Union based standardization (ITU-T) for our design and discuss future directions
      in wearable IoT.

PMID- 29060373
TI  - Reconstructing physical activity monitoring outcome measures using an interval
      sampling approach.
AB  - Smart-watches and wearables are becoming more and more popular and this
      popularity is resulting in an increased interest in their use in research and
      clinical settings for monitoring physical activity. The battery life of these
      devices is of some concern, especially when they are put under increased duress
      through the need to constantly sample from their accelerometers. In this paper a
      novel approach to sampling from the accelerometer is explored whereby the
      accelerometer is sampled in intervals to avoid constant sampling. Results show
      that through reducing the sampling time and sampling in discontinuous intervals
      that outcome measures of time spent in sedentary, moderate and vigorous activity
      can be reconstructed to within acceptable error levels when compared to the same
      outcome measures calculated from continually sampled data.

PMID- 29060374
TI  - Levels of activity identification & sleep duration detection with a wrist-worn
      accelerometer-based device.
AB  - In this study, a model for identifying the levels of physical activity (PA) with
      a wrist-worn accelerometer-based device has been proposed. The levels of
      identified PA have been categorized into rest/sleep, sedentary, light, moderate,
      and vigorous activity states by analyzing the data collected from 10 normal
      subjects. An activity-based sleep duration detection algorithm has been proposed
      and implemented thereafter to further distinguish activities between short period
      of rest and sleep. The model and method proposed in this study could be further
      used to monitor subject's daily PA status and sleep quality assessment in the
      future for various home-based healthcare applications.

PMID- 29060375
TI  - A monitoring system for walking rehabilitation after THR or TKR surgeries.
AB  - After total hip replacement and total knee replacement, patients are highly
      recommended to take walking rehabilitation, during which time, the weight loads
      on the limb should be limited to a certain range, which is difficult for patients
      to control on their own. To improve the accuracy and reliability of the
      traditional method for walking rehabilitation, we proposed a monitoring system
      comprised of pressure sensors, an analog digital converter, a micro-control unit,
      Bluetooth modules and a smart-phone application. Except for this application, the
      system is embedded in the customized shoes. When patients wear the shoes, the
      weight load data will be detected by the pressure sensors, and transmitted to the
      smart-phone application wirelessly in real time. Whenever the system detects too
      much weight on a patient's limb or an impending patient fall and abnormal gait,
      an algorithm, also proposed in this study, instructs the smart phone to sound an
      alarm. In addition, we present and test a gait evaluation algorithm that analyzes
      the patient's gait. Measurement results show that the accuracy of the system is
      0.5kg.

PMID- 29060376
TI  - A wearable sensor based multi-criteria-decision-system for real-time seizure
      detection.
AB  - This paper presents a wireless, low power and low cost two part wearable for real
      time epileptic seizure detection. Using parameters of Electro-cardiograph (ECG),
      Electro-dermal Activity (EDA), body motion and breathing rate (BR), a novel multi
      criteria-decision-system (MCDS) is proposed that reduces false alarms and true
      negatives. The combination of a chest and hand worn wearable continuously senses
      these parameters transmitting the data to a smart phone application via BLE 4.0
      where long-short-term-memory (LSTM) based anomaly detection algorithms and
      logistic classifiers decide on the occurrence of the seizure in real time. A 96%
      precision and 90% recall is achieved through testing on synthetic data.

PMID- 29060377
TI  - A novel method to monitor human stress states using ultra-short-term ECG spectral
      feature.
AB  - Electrocardiogram (ECG) signal represents autonomous nervous system responses to
      human emotional states. This research demonstrates that the spectral ECG features
      within ultra-short-term window duration (10-sec) could be utilized to monitor
      human emotional states. Experiments were conducted with five different stress
      protocols including mental and physical tasks. Experimental results showed
      feasible classification performance of ECG spectral features compared to that of
      HRV parameters. The averaged classification accuracy across 13 subjects and all
      stress protocols was 81.16% using Naive Bayes algorithm. In addition, the results
      showed stress responses in mental arithmetic tasks was the most separable from
      those in resting states (87.31%) compared to the other stress situations.

PMID- 29060378
TI  - A wearable action recognition system based on acceleration and attitude angles
      using real-time detection algorithm.
AB  - Falls are a main cause of trauma and death. The purpose of this study is to adopt
      unique resultant acceleration and attitude angles to distinguish falls from
      activities of daily life before impact. In this study, we developed a wearable
      action recognition system to acquire action data. The moving average filter was
      employed to deal with raw data, and then complementary filter was adopted to
      compromise sensor data for attitude angles. The real-time detection algorithm
      embedded in this device was applied to recognize six actions based on processed
      data. Eight subjects (five males, three females) participated in the experiment.
      The optimal features and related thresholds were extracted. In addition, the real
      time action detection results indicated that the real-time action recognition
      model reached an accuracy of 96.25%, with 98% for male and 93.3% for female.
      Thus, our device potentially achieves a high sensitivity of fall-related actions
      recognition.

PMID- 29060379
TI  - IoT/M2M wearable-based activity-calorie monitoring and analysis for elders.
AB  - With the growth of aging population, elder care service has become an important
      part of the service industry of Internet of Things. Activity monitoring is one of
      the most important services in the field of the elderly care service. In this
      paper, we proposed a wearable solution to provide an activity monitoring service
      on elders for caregivers. The system uses wireless signals to estimate calorie
      burned by the walking and localization. In addition, it also uses wireless motion
      sensors to recognize physical activity, such as drinking and restroom activity.
      Overall, the system can be divided into four parts: wearable device, gateway,
      cloud server, and caregiver's android application. The algorithms we proposed for
      drinking activity are Decision Tree (J48) and Random Forest (RF). While for
      restroom activity, we proposed supervised Reduced Error Pruning (REP) Tree and
      Variable Order Hidden Markov Model (VOHMM). We developed a prototype service
      Android app to provide a life log for the recording of the activity sequence
      which would be useful for the caregiver to monitor elder activity and its calorie
      consumption.

PMID- 29060380
TI  - High-density ear-EEG.
AB  - Ear-EEG enables recording of EEG in real-life environments in an unprecedented
      discreet and minimal obtrusive way. As ear-EEG are recorded from electrodes
      placed in or around the ear, the spatial coverage of the potential field on the
      scalp is inherently limited. Despite the limited spatial coverage, the potential
      field in-the-ear can still be measured in multiple points and thereby provide
      spatial information. We present a method to perform and visualize high-density
      ear-EEG recordings, and illustrate the method through recordings of auditory and
      visually evoked steady-state responses, for a single subject. The auditory and
      visually evoked responses showed distinctive differences in the response field in
      the ear, reflecting the very different locations of the underlying cortical
      sources. In conclusion, high-density ear-EEG can be used to investigate how
      different cortical sources maps to the ear, and provides a way to select optimal
      electrode positions for given brain phenomena.

PMID- 29060381
TI  - A model based analysis of optimality of sit-to-stand transition.
AB  - Objective assessment of mobility and effectiveness of interventions remains an
      open issue. Timed Up and Go (TUG) and 30 Second Chair Stand (30SCS) tests are
      routinely used in assessing mobility of subjects, but they provide a single
      parameter. Instrumenting subjects with wearable sensors enables a detailed
      mobility assessment. Specifically, we argue that instrumented sit-to-stand (S2ST)
      posture transitions during the TUG and 30SCS tests can be used to assess the
      strength and balance of subjects. In this paper we develop a personalized three
      segment model that quantifies torques/forces on the body and assesses optimality
      of each sit-to-stand transition. To characterize a S2ST transition we calculate
      action defined as an integral of mechanical energy over time. The theoretical
      optimal transition time can thus be determined for each person by finding the
      minimum action necessary for a S2ST transition. Our model assesses action during
      the S2ST transition using inputs from smartphone's inertial sensors, and
      calculates optimum S2ST transition time for a given body composition of a
      subject. Our experimental evaluation shows that healthy young subjects have
      posture transition times close to the optimal transition time generated by the
      model. We hypothesize that the optimality of posture transition provides an
      objective and potentially more accurate estimation of the mobility. We tested the
      model by evaluating optimum action and optimum S2ST transition time for 10
      geriatric patients undergoing a mobility improvement program by comparing their
      performance with the optimum performance generated by the model. This paper
      presents the model and possible use of the results to assess long-term changes in
      mobility of users.

PMID- 29060382
TI  - A novel, low cost, wearable contact-based device for breathing frequency
      monitoring.
AB  - This paper presents a device for breathing frequency assessment over the long
      period, based on low cost, wearable inertial units. Performances of the device
      were evaluated in static conditions on 9 healthy subjects and the estimated
      parameters were compared to those obtained with an already validated method
      (Optoelectronic Plethysmography). We obtained good correlation values (R2> 0.88)
      and low percentage errors (<;5%) for all the time-based parameters extracted.

PMID- 29060383
TI  - Gait speed estimation using Kalman Filtering on inertial measurement unit data.
AB  - Gait speed measurement is vital for diagnosis of motor disorder and monitoring
      the progress of patient rehabilitation. This study presents an algorithm for
      moderate distance gait speed measurement from data acquired with inertial motion
      sensors comprised of a tri-axial accelerometer and a tri-axial gyroscope. Gait
      speed was measured in four different speed levels set by a treadmill: 0.5, 1, 2,
      and 3 miles/hour. The calculated speed was tuned by implementing Kalman Filter.
      The performance of the proposed algorithm was evaluated by calculating the mean
      square error between estimated speed and the actual treadmill speed. The
      preliminary results obtained from various treadmill speeds suggest that proposed
      algorithm estimated speed in a reasonable accuracy. The average error rate was
      0.23 m/h which is nearly similar to other studies in this area. Algorithm
      performance evaluation for various speeds implied that the best performance was
      exhibited when the speed was set at 1 mile/hour. Moreover, the use of Kalman
      Filter helped to fine-tune the estimated speed by removing uncertainty and
      eventually provided a better approximation of the speed measured from the
      inertial measurement unit.

PMID- 29060384
TI  - Patient cloth with motion recognition sensors based on flexible piezoelectric
      materials.
AB  - In this paper, we introduce a patient cloth for position monitoring using motion
      recognition sensors based on flexible piezoelectric materials. The motion
      recognition sensors are embedded in three parts, which are the knee, hip and
      back, in the patient cloth. We use polyvinylidene fluoride (PVDF) as the flexible
      piezoelectric material for the sensors. By using the piezoelectric effect of the
      PVDF, we detect electrical signals when the cloth is bent or extended. We analyze
      the sensing values for our human motions by processing the sensor outputs in a
      custom-made program. Specifically, we focus on the transitions between standing
      and sitting, and sitting knee extension and supine position, which are important
      motions for patient monitoring.

PMID- 29060385
TI  - Towards an IoT-based upper limb rehabilitation assessment system.
AB  - Rehabilitation of stroke survivors has been increasing in importance in recent
      years with increase in the occurrence of stroke. However, current clinical
      classification assessment is time-consuming while the result is not accurate and
      varies across physicians. This paper introduces an IoT-based upper limb
      rehabilitation assessment system for stroke survivors based on wireless sensing
      sub-system, data cloud, computing cloud and software based on Android platform.
      The system can automatically perform objective assessment. It is designed for
      home rehabilitation as well as for the concept of graded rehabilitation therapy.

PMID- 29060386
TI  - Experimental characterization and analysis of the BITalino platforms against a
      reference device.
AB  - Low-cost hardware platforms for biomedical engineering are becoming increasingly
      available, which empower the research community in the development of new
      projects in a wide range of areas related with physiological data acquisition.
      Building upon previous work by our group, this work compares the quality of the
      data acquired by means of two different versions of the multimodal physiological
      computing platform BITalino, with a device that can be considered a reference. We
      acquired data from 5 sensors, namely Accelerometry (ACC), Electrocardiography
      (ECG), Electroencephalography (EEG), Electrodermal Activity (EDA) and
      Electromyography (EMG). Experimental evaluation shows that ACC, ECG and EDA data
      are highly correlated with the reference in what concerns the raw waveforms. When
      compared by means of their commonly used features, EEG and EMG data are also
      quite similar across the different devices.

PMID- 29060387
TI  - Wearable PPG sensor based alertness scoring system.
AB  - Quantifying mental alertness in today's world is important as it enables the
      person to adopt lifestyle changes for better work efficiency. Miniaturized
      sensors in wearable devices have facilitated detection/monitoring of mental
      alertness. Photoplethysmography (PPG) sensors through Heart Rate Variability
      (HRV) offer one such opportunity by providing information about one's daily
      alertness levels without requiring any manual interference from the user. In this
      paper, a smartwatch based alertness estimation system is proposed. Data collected
      from PPG sensor of smartwatch is processed and fed to machine learning based
      model to get a continuous alertness score. Utility functions are designed based
      on statistical analysis to give a quality score on different stages of alertness
      such as awake, long sleep and short duration power nap. An intelligent data
      collection approach is proposed in collaboration with the motion sensor in the
      smartwatch to reduce battery drainage. Overall, our proposed wearable based
      system provides a detailed analysis of alertness over a period in a systematic
      and optimized manner. We were able to achieve an accuracy of 80.1% for
      sleep/awake classification along with alertness score. This opens up the
      possibility for quantifying alertness levels using a single PPG sensor for better
      management of health related activities including sleep.

PMID- 29060388
TI  - Impedance spectroscopy of tripolar concentric ring electrodes with Ten20 and
      TD246 pastes.
AB  - Electrodes are used to transform ionic currents to electrical currents in
      biological systems. Modeling the electrode-electrolyte interface could help to
      optimize the performance of the electrode interface to achieve higher signal to
      noise ratios. There are previous reports of accurate models for single-element
      biomedical electrodes. In this paper, we measured the impedance on both tripolar
      concentric ring electrodes and standard cup electrodes by electrochemical
      impedance spectroscopy (EIS) using both Ten20 and TD246 electrode paste.
      Furthermore, we applied the model to prove that the model can predict the
      performance of the electrode-electrolyte interface for tripolar concentric ring
      electrodes (TCRE) that are used to record brain signals.

PMID- 29060389
TI  - Using cognitive fit theory to evaluate patient understanding of medical images.
AB  - Patients are increasingly presented with their health data through patient
      portals in an attempt to engage patients in their own care. Due to the large
      amounts of data generated during a patient visit, the medical information when
      shared with patients can be overwhelming and cause anxiety due to lack of
      understanding. Health care organizations are attempting to improve transparency
      by providing patients with access to visit information. In this paper, we present
      our findings from a research study to evaluate patient understanding of medical
      images. We used cognitive fit theory to evaluate existing tools and images that
      are shared with patients and analyzed the relevance of such sharing. We discover
      that medical images need a lot of customization before they can be shared with
      patients. We suggest that new tools for medical imaging should be developed to
      fit the cognitive abilities of patients.

PMID- 29060390
TI  - Computing the variations in the self-similar properties of the various gait
      intervals in Parkinson disease patients.
AB  - This study has investigated the stride, swing, stance and double support
      intervals of gait for Parkinson's disease (PD) patients with different levels of
      severity. Self-similar properties of the gait signal were analyzed to investigate
      the changes in the gait pattern of the healthy and PD patients. To understand the
      self-similar property, detrended fluctuation analysis was performed. The analysis
      shows that the PD patients have less defined gait when compared to healthy. The
      study also shows that among the stance and swing phase of stride interval, the
      self-similarity is less for swing interval when compared to the stance interval
      of gait and decreases with the severity of gait. Also, PD patients show decreased
      self-similar patterns in double support interval of gait. This suggest that there
      are less rhythmic gait intervals and a sense of urgency to remain in support
      phase of gait by the PD patients.

PMID- 29060391
TI  - CNN based approach for activity recognition using a wrist-worn accelerometer.
AB  - In recent years, significant advancements have taken place in human activity
      recognition using various machine learning approaches. However, feature
      engineering have dominated conventional methods involving the difficult process
      of optimal feature selection. This problem has been mitigated by using a novel
      methodology based on deep learning framework which automatically extracts the
      useful features and reduces the computational cost. As a proof of concept, we
      have attempted to design a generalized model for recognition of three fundamental
      movements of the human forearm performed in daily life where data is collected
      from four different subjects using a single wrist worn accelerometer sensor. The
      validation of the proposed model is done with different pre-processing and noisy
      data condition which is evaluated using three possible methods. The results show
      that our proposed methodology achieves an average recognition rate of 99.8% as
      opposed to conventional methods based on K-means clustering, linear discriminant
      analysis and support vector machine.

PMID- 29060392
TI  - The timing of theta phase synchronization accords with vigilant attention.
AB  - Vigilant attention plays an important role in some industries and everyday life.
      However, its mechanism relating to phase synchronization of cortical oscillations
      is still unknown, which hinders the development of predicting and preventing
      vigilant attentional deficit. This study utilized psychomotor vigilance test
      (PVT) to elicit vigilance decrement. High and low levels of vigilant attention
      were represented by short and long reaction time, respectively.
      Electroencephalogram (EEG) was collected and phase synchronization between
      prefrontal and parietal cortices was analyzed by using debiased weighted phase
      lag index (dWPLI). The result suggests that vigilant attention of high level has
      earlier timing of theta (4-8Hz) phase synchronization, compared with that of low
      level. We concluded that phase synchronization may relate closely with the
      variation of vigilant attention.

PMID- 29060393
TI  - Role of multisensory stimuli in vigilance enhancement- a single trial event
      related potential study.
AB  - Development of interventions to prevent vigilance decrement has important
      applications in sensitive areas like transportation and defence. The objective of
      this work is to use multisensory (visual and haptic) stimuli for cognitive
      enhancement during mundane tasks. Two different epoch intervals representing
      sensory perception and motor response were analysed using minimum variance
      distortionless response (MVDR) based single trial ERP estimation to understand
      the performance dependency on both factors. Bereitschaftspotential (BP) latency
      L3 (r=0.6 in phase 1 (visual) and r=0.71 in phase 2 (visual and haptic)) was
      significantly correlated with reaction time as compared to that of sensory ERP
      latency L2 (r=0.1 in both phase 1 and phase 2). This implies that low performance
      in monotonous tasks is predominantly dependent on the prolonged neural
      interaction with the muscles to initiate movement. Further, negative relationship
      was found between the ERP latencies related to sensory perception and
      Bereitschaftspotential (BP) and occurrence of epochs when multisensory cues are
      provided. This means that vigilance decrement is reduced with the help of
      multisensory stimulus presentation in prolonged monotonous tasks.

PMID- 29060394
TI  - Automatic visual impairment detection system for age-related eye diseases through
      gaze analysis.
AB  - Visual impairment associated with Age-related Macular Degeneration (AMD) often
      results in a central scotoma which is an alteration in the central vision,
      leading to distortion or loss of vision. Current methods for assessing visual
      performance such as Amsler grid and Microperimetry are typically manual and have
      limitations as an indicator of visual field. In this paper, we present an
      automated system for detecting visual impairment through gaze tracking (AVIGA).
      Two types of assessments namely, Impulse Stimuli Response (ISR) test and Pursuit
      Stimuli Response (PSR) test were implemented in AVIGA system. A Support Vector
      Regression (SVR)-based approach is applied on the assessment results to
      differentiate the severity of visual impairment. The results show that AVIGA
      system is well-correlated to visual acuity test (VA) and performs better in
      identifying presence of visual impairments in eyes, compared to Microperimetry.

PMID- 29060395
TI  - Towards understanding addiction factors of mobile devices: An eye tracking study
      on effect of screen size.
AB  - Mobile devices addiction has been an important research topic in cognitive
      science, mental health, and human-machine interaction. Previous works observed
      mobile device addiction by logging mobile devices activity. Although immersion
      has been linked as a significant predictor of video game addiction, investigation
      on addiction factors of mobile device with behavioral measurement has never been
      done before. In this research, we demonstrated the usage of eye tracking to
      observe effect of screen size on experience of immersion. We compared subjective
      judgment with eye movements analysis. Non-parametric analysis on immersion score
      shows that screen size affects experience of immersion (p<;0.05). Furthermore,
      our experimental results suggest that fixational eye movements may be used as an
      indicator for future investigation of mobile devices addiction. Our experimental
      results are also useful to develop a guideline as well as intervention strategy
      to deal with smartphone addiction.

PMID- 29060396
TI  - Effects of galvanic skin response feedback on user experience in gaze-controlled
      gaming: A pilot study.
AB  - Eye-tracking (ET) is one of the most intuitive solutions for enabling people with
      severe motor impairments to control devices. Nevertheless, even such an effective
      assistive solution can detrimentally affect user experience during demanding
      tasks because of, for instance, the user's mental workload - using gaze-based
      controls for an extensive period of time can generate fatigue and cause
      frustration. Thus, it is necessary to design novel solutions for ET contexts able
      to improve the user experience, with particular attention to its aspects related
      to workload. In this paper, a pilot study evaluates the effects of a relaxation
      biofeedback system on the user experience in the context of a gaze-controlled
      task that is mentally and temporally demanding: ET-based gaming. Different
      aspects of the subjects' experience were investigated under two conditions of a
      gaze-controlled game. In the Biofeedback group (BF), the user triggered a command
      by means of voluntary relaxation, monitored through Galvanic Skin Response (GSR)
      and represented by visual feedback. In the No Biofeedback group (NBF), the same
      feedback was timed according to the average frequency of commands in BF. After
      the experiment, each subject filled out a user experience questionnaire. The
      results showed a general appreciation for BF, with a significant between-group
      difference in the perceived session time duration, with the latter being shorter
      for subjects in BF than for the ones in NBF. This result implies a lower mental
      workload for BF than for NBF subjects. Other results point toward a potential
      role of user's engagement in the improvement of user experience in BF. Such an
      effect highlights the value of relaxation biofeedback for improving the user
      experience in a demanding gaze-controlled task.

PMID- 29060397
TI  - Stimulation time determination for lower limb FES by using gait event and a
      "delay".
AB  - Lower limb neuroprostheses for motor function rehabilitation, especially the drop
      foot stimulator, uses sensors to turn on or off stimulus pulse sequence during
      hemiplegic patient's locomotion. This triggering method with fixed stimulus pulse
      output control may result in uncoordinated limb movement in the lower limb
      rehabilitation training. The purpose of this paper was to investigate the
      reliability of stimulus onset determination using inertial measurement units
      (IMUs), and a dynamic control algorithm based on gait event detection and walking
      speed was proposed. In our study, two different equipments were employed to
      record surface EMG (sEMG) of synergist muscles (tibialis anterior and medial
      gastrocnemius) and IMU sensor signals. Several detection methods for muscle
      activity onset-time were compared and analyzed to obtain a suitable onset
      detection method. A dynamic "Delay" time between heel strike event and muscle
      activity onset was obtained through an algorithm, and its relationship with
      walking speed was determined using data fitting.

PMID- 29060398
TI  - Characterization of the pierce two-node model under exercise load by parameter
      optimization toward construction of a modified thermal model for persons with
      spinal cord injury.
AB  - In this study, we attempted to develop a thermal model for estimating a body
      temperature in persons with spinal cord injury (SCI) during exercise. To clarify
      requisites for the SCI thermal model, we compared actual body temperature of SCI
      subjects with that calculated with a standard thermal model, that is, the Pierce
      two-node model. Model optimization by the parameter search method was able to fit
      the model-estimated skin and core temperature with those in able-bodied subjects
      during repeated exercise and rest. However, there remained a phase shift between
      actual and model-estimated core temperature trends in SCI subjects even after the
      optimization. The comparison of the optimized parameter combinations revealed
      that the Pierce two-node model was able to express loss of sweating in the SCI
      subjects, but unable to express delay in heat accumulation and dissipation. These
      results suggest that SCI thermal model requires additional nodes that express the
      speed and extent of heat transfer in the body of SCI persons.

PMID- 29060399
TI  - Evaluation of different cochlear implants in unilateral hearing patients during
      word listening tasks: A brain connectivity study.
AB  - Advanced methodologies used for the biomedical signal interpretation allow using
      cerebral signals to assess important cognitive functions in humans. In the
      present study, as parameter of cerebral effort, has been employed the isolated
      effective coherence, in order to estimate the effective connectivity and network
      organization. The hypothesis was that the lower the number of inter-connections
      engaged, the lower the cerebral effort induced by the experimental condition. In
      the present research this index has been applied to test the reaction to the use
      of different cochlear implant processors (Freedom, CP810 and CP910 - Cochlear
      Ltd), with the aim to identify the most performing device during a word in noise
      recognition task. Results support the capability of identifying the device
      eliciting less brain area connections. In particular, the CP910 was the processor
      inducing the lower number of inter-connections among the tested ones. This
      investigation appeared to be worthy, since representing a tool to identify
      devices that would make available user's cognitive resources for additional
      tasks, a matter susceptible of generalization to various fields of application.
      The employment of the cerebral signals therefore open the way to the evaluation
      of the impact of different sensors and prosthetic devices, also using
      connectivity measures.

PMID- 29060400
TI  - Estimation of joint position error.
AB  - Joint position error (JPE) is frequently used to assess proprioception in
      rehabilitation and sport science. During position-reposition tests the subject is
      asked to replicate a specific target angle (e.g. 30 degrees  of knee flexion) for
      a specific number of times. The aim of this study is to find an effective method
      to estimate JPE from the joint kinematic signal. Forty healthy subjects were
      tested to assess knee joint position sense. Three different methods of JPE
      estimation are described and compared using a hierarchical clustering approach.
      Overall, the 3 methods showed a high degree of similarity, ranging from 88% to
      100%. We concluded that it is preferable to use the more user-independent method,
      in which the operator does not have to manually place "critical" markers.

PMID- 29060401
TI  - Measuring vigilance decrement using computer vision assisted eye tracking in
      dynamic naturalistic environments.
AB  - Eye tracking offers a practical solution for monitoring cognitive performance in
      real world tasks. However, eye tracking in dynamic environments is difficult due
      to high spatial and temporal variation of stimuli, needing further and thorough
      investigation. In this paper, we study the possibility of developing a novel
      computer vision assisted eye tracking analysis by using fixations. Eye movement
      data is obtained from a long duration naturalistic driving experiment. Source
      invariant feature transform (SIFT) algorithm was implemented using VLFeat toolbox
      to identify multiple areas of interest (AOIs). A new measure called 'fixation
      score' was defined to understand the dynamics of fixation position between the
      target AOI and the non target AOIs. Fixation score is maximum when the subjects
      focus on the target AOI and diminishes when they gaze at the non-target AOIs.
      Statistically significant negative correlation was found between fixation score
      and reaction time data (r =-0.2253 and p<;0.05). This implies that with vigilance
      decrement, the fixation score decreases due to visual attention shifting away
      from the target objects resulting in an increase in the reaction time.

PMID- 29060402
TI  - Correlation of reaction time and EEG log bandpower from dry frontal electrodes in
      a passive fatigue driving simulation experiment.
AB  - Fatigue is one of the causes of falling asleep at the wheel, which can result in
      fatal accidents. Thus, it is necessary to have practical fatigue detection
      solutions for drivers. In literature, electroencephalography (EEG) along with the
      surrogate measure of reaction time (RT) has been used to develop fatigue
      detection algorithms. However, these solutions are often based upon wet multi
      channel EEG electrodes which are not feasible or practical for drivers. Using dry
      electrodes and headband like designs would be better. Hence, this study aims to
      investigate the correlation of EEG log bandpower against RT via a Muse headband
      which has dry frontal EEG electrodes. 31 subjects underwent an hour-long driving
      simulation experiment with car deviation events. Based on the video and EEG data,
      5 'Sleepy' and 5 'Alert' subjects are identified and analyzed. A differential
      signal between Fp1 and Fp2 is computed so as to remove the effects of eye blinks,
      and is analyzed for correlation with RT. Significant positive correlation is
      found for log delta (1-4 Hz) bandpower, and significant negative correlations for
      log theta (4-8 Hz) and alpha (8-12 Hz) bandpowers, but the positive correlation
      of log beta (12-30 Hz) bandpower with RT is not significant. This is a good first
      step towards building a practical fatigue detection solution for drivers in the
      future.

PMID- 29060403
TI  - Differences in lower limb muscle activation patterns during Sit to Stand Task for
      different heel heights.
AB  - The purpose of this study was to investigate differences in lower limb muscle
      activation patterns for females wearing shoes with different heel heights during
      Sit to Stand Task (STS). Ten female participants with no prior history of
      neurological disorders participated in this study. Surface electromyography
      (sEMG) characteristics were recorded for four different heel heights (ranging
      from 4cm to 10cm) while performing the STS task. Signal processing analysis
      suggests that muscle activities increases on elevated heel heights, which may
      induce muscle imbalance for frequent STS tasks. In addition, results of muscle
      utilisation (percentage) for different heel heights suggest that lower limb
      muscles tend to compensate in order to maintain postural balance.

PMID- 29060404
TI  - Learning classifier to evaluate movement quality in unassisted pick-and-place
      exercises for post-stroke patients: A preliminary study.
AB  - The use of service robots is gaining increasing interest in stroke rehabilitation
      research. In autonomous robot therapy sessions, it is important to monitor the
      qualitative motor performance of the patient and to evaluate if therapeutically
      desirable movements are reinforced as per the therapist's instructions. Research
      on computational means to address this issue has received little attention,
      despite the acknowledged importance thereof. This paper poses the question of
      whether the subjective evaluation of the therapist on the qualitative motor
      performance of the individual patient can be modelled. In an attempt to answer
      this question, we frame it as a supervised machine learning problem and
      investigate if kinematic sensor readings to the subjective evaluation of the
      therapist can be correlated. We further examine if the personalized classifier
      trained with the data of the individual patient should be favored over the
      general classifier. Our preliminary results suggest that, given kinematic
      observation, trained classifiers may be able to imitate the evaluation of the
      therapist for the movement quality of the post-stroke patient. In our
      experiments, the general classifier outperformed the personalized classifiers,
      however, further investigation is necessary to generalize this finding.

PMID- 29060405
TI  - EEG-based emergency braking intention prediction for brain-controlled driving
      considering one electrode falling-off.
AB  - This paper proposes a novel method of electroencephalography (EEG)-based driver
      emergency braking intention detection system for brain-controlled driving
      considering one electrode falling-off. First, whether one electrode falls off is
      discriminated based on EEG potentials. Then, the missing signals are estimated by
      using the signals collected from other channels based on multivariate linear
      regression. Finally, a linear decoder is applied to classify driver intentions.
      Experimental results show that the falling-off discrimination accuracy is 99.63%
      on average and the correlation coefficient and root mean squared error (RMSE)
      between the estimated and experimental data are 0.90 and 11.43 MUV, respectively,
      on average. Given one electrode falls off, the system accuracy of the proposed
      intention prediction method is significantly higher than that of the original
      method (95.12% VS 79.11%) and is close to that (95.95%) of the original system
      under normal situations (i. e., no electrode falling-off).

PMID- 29060406
TI  - The role of nonmotor brain regions during human motor control.
AB  - Neural prostheses have generally relied on signals from cortical motor regions to
      control reaching movements of a robotic arm. However, little work has been done
      in exploring the involvement of nonmotor cortical and associative regions during
      motor tasks. In this study, we identify regions which may encode direction during
      planning and movement of a center-out motor task. Local field potentials were
      collected using stereoelectroencephalography (SEEG) from nine epilepsy patients
      implanted with multiple depth electrodes for clinical purposes. Spectral analysis
      of the recorded data was performed using nonparametric statistical techniques to
      identify regions that may encode direction of movements during the motor task.
      The analysis revealed several nonmotor regions; including the right insular
      cortex, right temporal pole, right superior parietal lobule, and the right
      lingual gyrus, that encode directionality before and after movement onset. We
      observed that each of these regions encode direction in different frequency
      bands. This preliminary study suggests that nonmotor regions may be useful in
      assisting in neural prosthetic control.

PMID- 29060407
TI  - Influence of pre-processing in the extraction of muscle synergies during human
      locomotion.
AB  - The extraction of muscle synergies in human locomotion may be biased by the kind
      of pre-processing applied to electromyographic (EMG) data. The aim of this
      contribution is to analyze the differences in the muscle synergies extracted
      using a standard pre-processing procedure and a new procedure. The new procedure
      is based on the selection of the muscle's principal activations (necessary
      actuations of the muscle to accomplish its specific biomechanical task during
      gait), discarding secondary activations (with an auxiliary function in motor
      control). EMG signals were recorded from 12 muscles of a healthy volunteer who
      was asked to walk, at self-selected pace, for 5 minutes. A dataset of 193 gait
      cycles was collected and divided into 19 epochs of 10 concatenated gait cycles.
      The application of the new pre-processing procedure provided 5 instead of 6
      muscle synergies accurately reconstructing the original EMG data matrix, and
      clearer and more stable neural activation commands. The new preprocessing
      procedure may be easily extended to the extraction of muscle synergies in other
      cyclic movements, such as running, stair climbing, cyclo-ergometer exercising,
      and swimming.

PMID- 29060408
TI  - Features selection for Bayes classification of prolonged fatigue on rectus
      femoris muscle.
AB  - Sports training is very important to athletes in improving and maintaining their
      performances. It commonly involves high intensity exercise and requires longer
      time for fatigue to recover, compares to normal activity. During training,
      adequate rest is essential to allow recuperation and build body strength.
      Unfortunately, inadequate rest exposes the body to prolonged fatigue (PF). Hence,
      this condition needs to be managed accordingly to avoid chronic fatigue syndrome.
      Recent findings indicate that there are strong characteristics on surface EMG
      under PF conditions. Currently, the assessment is limited to glycogen breakdown,
      the existence of lactate and soreness. In this study, twenty participants were
      recruited to perform five days intensive training (IT) to induce more PF signs.
      The IT conducted was based on Bruce Protocol treadmill test. It was discovered
      that the IT successfully induces soreness, unexplained lethargy and performance
      decrement. Surface EMG were collected from rectus femoris muscle during daily pre
      and post treadmill tests. Four features were extracted from the surface EMG; mean
      frequency (Fmean), median frequency (Fmed), root mean square (RMS) and mean
      absolute value (MAV). The results indicated that all features during post
      exercise had greater value under PF condition and it was significant at P<;0.05.
      The features then were classified in accordance to Bayes. The results also showed
      that Fmed and MAV features offered good performance with 83.1% accuracy, 84.6%
      specificity and 80% of precision.

PMID- 29060409
TI  - Importance of muscle selection for EMG signal analysis during upper limb
      rehabilitation of stroke patients.
AB  - Current work highlights the importance of muscle selection to evaluate paralysis
      and recovery level of stroke patients when comparing synergies of affected and
      non-affected side of the body. The proposed method allows the selection of
      important muscles that highly contribute to the specific movements according to
      the power and frequency distribution of the electromyographic signals.. Users
      participating performed steering-wheel-based therapy focused on upper limb
      rehabilitation. Final results show that with the appropriate muscles selection,
      it is possible to compute a Similarity Index between right and left arms (during
      symmetric motion) associated to the level of paralysis and potential recovery of
      a given subject.

PMID- 29060410
TI  - Variance distribution analysis of surface EMG signals based on marginal maximum
      likelihood estimation.
AB  - This paper describes the estimation and analysis of variance distribution of
      surface electromyogram (EMG) signals based on a stochastic EMG model. With the
      assumption that EMG signals at a certain time follow Gaussian distribution, their
      variance is handled as a random variable that follows inverse gamma distribution,
      and noise superimposed onto this variance can be expressed accordingly. The paper
      proposes variance distribution estimation based on marginal likelihood
      maximization of EMG signals. A simulation experiment using artificially generated
      signals to verify its accuracy indicated that the method can estimate variance
      distribution with high accuracy for a wide range of variance distribution
      shaping. Analysis of variance distribution using measured EMG signals revealed
      the relationship between muscle force and variance distribution involving signal
      dependent noise.

PMID- 29060411
TI  - Influence of trans-spinal magnetic stimulation in electrophysiological recordings
      for closed-loop rehabilitative systems.
AB  - Recent studies have shown the feasibility of spinal cord stimulation (SCS) for
      motor rehabilitation. Currently, there is an increasing interest in developing
      closed-loop systems employing SCS for lower-limb recovery. These closed-loop
      systems are based on the use of neurophysiological signals to modulate the
      stimulation. It is known that electromagnetic stimulation can introduce
      undesirable noise to the electrophysiological recordings. However, there is
      little evidence about how electroencephalographic (EEG) or electromyographic
      (EMG) activities are corrupted when a trans-spinal magnetic stimulation is
      applied. This paper studies the effects of magnetic SCS in EEG and EMG activity.
      Furthermore, a median filter is proposed to ameliorate the effects of the
      artifacts, and to preserve the neural activity. Our results show that SCS can
      affect both EEG and EMG, and that, while the median filter works well to clean
      the EEG activity, it did not improve the contaminations of the EMG activity. The
      obtained results underline the need of cleaning EMG and EEG signals contaminated
      by SCS, which is essential for optimal closed-loop rehabilitation.

PMID- 29060412
TI  - Evaluation of postural instability in stroke patient during quiet standing.
AB  - This study was designed to investigate the postural instability in stroke
      survivals during quiet standing. Eleven stroke patients and 11 healthy volunteers
      (gender- and age-matched) were recruited for this experiment. The center of
      pressure (COP) signals from both planta in anterior-posterior (AP) and medial
      lateral (ML) directions were recorded using a three-dimensional motion capture
      system (BTS Bioengineering Corp, Italy) when subjects stood on the two adjacent
      force platforms quietly with their eyes open (EO) for 30 s and with their eyes
      close (EC) for another 30 s. The standard deviation (SD) for the two limbs and
      the inter-limb cross correlation-coefficient (CC) of COP series were calculated
      under EO and EC conditions, respectively. Patients showed significant differences
      in SD of AP-COP between two sides under EO (p <; 0.05) and EC (p <; 0.001)
      conditions. The SD of the ML-COP on non-paretic limb of patients was higher than
      that of controls under EC (p <; 0.05). Lower CC values of AP-COP was found in
      patients versus controls under two vision conditions (p <; 0.05), and the values
      in two groups increased significantly after removal of vision information (p <;
      0.05). Stroke led to an increased postural sway and decreased inter-limb
      coordination during quiet standing. This study may facilitate the evaluation of
      the standing instability in stroke survivors and may improve the strategies for
      rehabilitation.

PMID- 29060413
TI  - Influence of light finger touch on postural stability during upright stance with
      cold-induced plantar hypoesthesia.
AB  - The present study investigated the influence of light finger touch on postural
      stability during an upright stance with or without cold-induced plantar
      hypoesthesia. Participants were 21 healthy right-handed men (20-33 years),
      randomly assigned to a normal temperature group (NML-group; n = 11) or cold
      induced plantar hypoesthesia group (COLD-group; n = 10). Participants performed
      two standing tasks with their eyes closed: 1) stand upright with the feet
      comfortably apart (normal standing); and 2) with the feet together in a side-by
      side stance (Romberg standing). The order of the tasks was randomized across
      participants. After a rest period, they were asked to perform each standing task
      and let their right index finger lightly touch the fixed surface. Before the each
      task, participants in the COLD group were conducted a plantar intermediate
      hypothermic exposure. Postural sway was decreased by providing additional haptic
      sensory input through the light touching regardless of standing task difficulty
      with a normal plantar temperature. Although postural sway under plantar
      hypoesthesia is decreased by light touching, the effect was greater during the
      difficult posture task. These results suggest that, when the sensory information
      from the plantar surface is decreased, additional haptic input from the hand or
      finger might provide supplementary information about the relative changes in
      one's own body orientation. Therefore, sensory information provided by touching
      became relatively more important to maintaining postural control during the
      relatively difficult postural task performed under the reduced plantar
      sensitivity condition.

PMID- 29060414
TI  - Entropy of surface EMG reflects object weight in grasp-and-lift task.
AB  - Fingertip force coordination is crucial to the success of grasp-and-lift tasks.
      In the development of motor prosthesis for daily applications, the ability to
      accurately classify the desired grasp-and-lift from multi-channel surface
      electromyography (sEMG) is essential. In order to extract reliable indicators for
      fingertip force coordination, we searched an extensive set of sEMG features for
      the optimal subset of relevant features. Using mutual information based feature
      selection we found that a subset of not more than 10 sEMG features selected from
      over seven thousand, could effectively classify object weights in grasp-and-lift
      tasks. Average classification accuracies of 82.53% in the acceleration phase and
      88.61% in the isometric contraction phase were achieved. Furthermore, sEMG
      features associated with object weights and common across individuals were
      identified. These time-domain features (entropy, mean/median absolute deviation,
      pNNx) can be calculated efficiently, providing possible new indicators.

PMID- 29060415
TI  - Muscle synergy analysis in dart throwing.
AB  - This study aims to analyze muscle synergies in darts throwing movement to clarify
      how the central nervous system (CNS) controls muscle activation to produce
      complicated motion. Activities of 10 different muscles on upper limb were
      recorded through surface electromyography (EMG) electrodes from four participants
      with less experience of dart throwing. Subsequently, non-negative matrix
      factorization (NNMF) was applied to the collected EMG signals for muscle synergy
      analysis. Results showed that three muscle synergies could explain sufficiently
      the observed EMG data, with determination coefficient r2 = 0.91 +/- 0.02 across
      four subjects. However, it was found that there was significant difference in
      terms of patterns of both muscle synergies and activation coefficients between
      participants, which might reflect different neuromuscular control strategies in
      dart throwing.

PMID- 29060416
TI  - Estimation of joint angle based on surface electromyogram signals recorded at
      different load levels.
AB  - To control upper-limb exoskeletons and prostheses, surface electromyogram (sEMG)
      is widely used for estimation of joint angles. However, the variations in the
      load carried by the user can substantially change the recorded sEMG and
      consequently degrade the accuracy of joint angle estimation. In this paper, we
      aim to deal with this problem by training classification models using a pool of
      sEMG data recorded from all different loads. The classification models are
      trained as either subject-specific or subject-independent, and their results are
      compared with the performance of classification models that have information
      about the carried load. To evaluate the proposed system, the sEMG signals are
      recorded during elbow flexion and extension from three participants at four
      different loads (i.e. 1, 2, 4 and 6 Kg) and six different angles (i.e. 0, 30, 60,
      90, 120, 150 degrees). The results show while the loads were assumed unknown and
      the applied training data was relatively small, the proposed joint angle
      estimation model performed significantly above the chance level in both the
      subject-specific and subject-independent models. However, transferring from known
      to unknown load in the subject-specific classifiers leads to 20% to 32% loss in
      the average accuracy.

PMID- 29060417
TI  - Spatiotemporal properties of magnetic fields induced by auditory speech sound
      imagery and perception.
AB  - Brain computer interface (BCI) technologies, which enable direct communication
      between the brain and external devices, have been developed. BCI technology can
      be utilized in neural prosthetics to restore impaired movement, including speech
      production. However, most of the BCI systems that have been developed are the
      "P300-speller" type, which can only detect objects that users direct his/her
      attention at. To develop more versatile BCI systems that can detect a user's
      intention or thoughts, the brain responses associated with verbal imagery need to
      be clarified. In this study, the brain magnetic fields associated with auditory
      verbal imagery and speech hearing were recorded using magnetoencephalography
      (MEG) carried out on 8 healthy adults. Although the magnetic fields lagged
      slightly and were long-lasting, significant deflections were observed even for
      verbal imagery, in the temporal regions, as well as for actual speech hearing.
      Also, sources for the deflections were localized in the association auditory
      cortices. Cross-correlations were calculated between envelopes of the
      imagined/presented speech sound and the evoked brain responses in the temporal
      areas. Measurable correlations were obtained for the presented speech sound;
      however, no significant correlations were observed for the imagined speech sound.
      These results indicate that auditory verbal imagery undoubtedly activates the
      auditory cortex, at least, and generates some observable neural responses.

PMID- 29060418
TI  - Prefrontal cortical activation while viewing urban and garden scenes: A pilot
      fNIRS study.
AB  - Recent studies have shown that pleasant and unpleasant emotions could be detected
      through functional Near-Infrared Spectroscopy (fNIRS). This study investigates
      the prefrontal cortical activation in human subjects while they were viewing
      urban and garden scenes. A multi-channel continuous wave fNIRS system was used to
      record the prefrontal cortical activations from seven subjects. During the data
      collection, the subjects viewed 40 trials of video clips. In each trial, the
      subjects viewed a video of randomized urban or garden scenes for 30s followed by
      30s of idle scene which showed a dark blue progress bar on black background on
      the screen. NIRS-SPM is employed to work out the changes of hemoglobin response
      and the prefrontal cortical activations were generated using group analysis based
      on the contrasts of urban versus idle, garden versus idle and urban versus
      garden. The activation for the contrast of urban versus garden showed an increase
      of oxy-hemoglobin on the right area of the prefrontal cortex with p <; 0.05. This
      preliminary result showed that the garden scene might provide a pleasant and less
      stressful experience as compared to the urban scene for subjects. This suggests
      the possibility of using a NIRS-based Brain-Computer Interface to detect subject
      preferences of different scenes.

PMID- 29060419
TI  - Physiological fluctuations show frequency-specific networks in fNIRS signals
      during resting state.
AB  - Physiological fluctuations are commonly present in functional studies of
      hemodynamic response such as functional magnetic resonance imaging (fMRI) and
      functional near-infrared spectroscopy (fNIRS). However, the effects of these
      signals in neural mechanisms are not fully understood. Thus, the aim of this
      study is to propose that frequency-specific networks exist in the somatosensory
      region within the frequency range of physiological fluctuations. We used a
      wavelet coherence approach to identify functional connectivity between cortical
      regions. Based on the spectral response, four frequency bands were identified:
      cardiac (0.8-1.5 Hz), respiration (0.16-0.6 Hz), low frequency oscillations (LFO)
      (0.04-0.15 Hz), and very low frequency oscillations (VLFO) (0.0130.04 Hz). Eight
      cortical networks were revealed after ipsilateral and contralateral analysis to
      evaluate connectivity in each frequency band. The ANOVA analysis proved the
      adequacy of the connectivity map for all frequencies bands. Finally, these
      findings suggest possible frequency-specific organizations within the frequency
      bands of physiological fluctuations in the resting human brain.

PMID- 29060420
TI  - Analysis of cognitive fatigue using EEG parameters.
AB  - Continuous and repetitive performance of a task is likely to induce a drop in
      alertness levels of an individual. Changes in Electroencephalogram (EEG) have
      been proposed in literature as a marker of alertness during repeated performance
      of a cognitive task set. The present paper investigates the increase in fatigue
      levels and resultant drop in alertness of subjects during continuous performance
      of cognitive tasks by analyzing changes in energy of EEG frequency bands. The
      trends reflected in the EEG parameters correspond to a gradual increase in
      fatigue levels of subjects with increase in cognitive loading.

PMID- 29060421
TI  - Cortical activity changes as related to oral irritation-an fNIRS study.
AB  - We present the first investigation of how the cortical regions of the brain
      respond to the sensations related to oral irritation, using functional near
      infrared spectroscopy (fNIRS). fNIRS is used to record irritant-induced
      activities in the prefrontal and somatosensory regions of nine healthy
      individuals. Two types of solutions, irritant-free and soft tissue-irritant
      contained, are adopted as the stimuli for the control and task experiments,
      respectively. Our findings reveal that both somatosensory and prefrontal regions
      show activity as a result of oral irritation. Furthermore, using moving window
      analysis, we identify the time interval during which the largest number of
      channels (indicative of high involvement of cortical regions) show irritant
      induced activity. Our results indicate that fNIRS can be used to study brain
      activities related to oral irritation.

PMID- 29060422
TI  - Correlated alpha activity with the facial expression processing network in a
      simultaneous EEG-fMRI experiment.
AB  - The relationship between EEG and fMRI data is poorly covered in the literature.
      Extensive work has been conducted in resting-state and epileptic activity,
      highlighting a negative correlation between the alpha power band of the EEG and
      the BOLD activity in the default-mode-network. The identification of an
      appropriate task-specific relationship between fMRI and EEG data for predefined
      regions-of-interest, would allow the transfer of interventional paradigms (such
      as BOLD-based neurofeedback sessions) from fMRI to EEG, enhancing its application
      range by lowering its costs and improving its flexibility. In this study, we
      present an analysis of the correlation between task-specific alpha band
      fluctuations and BOLD activity in the facial expressions processing network. We
      characterized the network ROIs through a stringent localizer and identified two
      clusters on the scalp (one frontal, one parietal-occipital) with marked alpha
      fluctuations, related to the task. We then check whether such power variations
      throughout the time correlate with the BOLD activity in the network. Our results
      show statistically significant negative correlations between the alpha power in
      both clusters and for all the ROIs of the network. The correlation levels have
      still not met the requirements for transferring the protocol to an EEG setup, but
      they pave the way towards a better understand on how frontal and parietal
      occipital alpha relates to the activity of the facial expressions processing
      network.

PMID- 29060423
TI  - An artificial neural network model for the evaluation of carotid artery stenting
      prognosis using a national-wide database.
AB  - Stroke is a serious health problem in many countries. About 20% of ischemia
      stroke involves carotid stenosis. Neck carotid ultrasound is fast, secure and
      convenient way to detect carotid artery stenosis. Carotid artery stenting (CAS)
      has become a popular treatment for cerebrovascular stenosis in recent years.
      However, CAS may also induce the occurrence of major adverse cardiovascular
      events (MACE) in older patients. Hence the evaluation the CAS prognosis is
      important. In this study, we attempted to construct a model for the evaluation of
      CAS prognosis by artificial neural network (ANN). The data of 317 patients from
      Taiwan Nation Health Insurance Research Database (NHIRD) was used to train and
      test the constructed ANN model. The input features contain 13 clinical risk
      factors and the output is the occurrence of MACE. In results, an ANN model of
      multilayer perceptron with 18 neurons in hidden layer was developed. The
      performance of this model is with sensitivity 89.4%, specificity 57.4%, and
      accuracy 82.5% in testing group as well as with sensitivity 85.8%, specificity
      60.8% and accuracy 80.76% in overall patients. The results revealed that the
      created ANN model achieved a good performance in prediction of MACE in patients
      needing CAS treatment. Such a model will be helpful for prevention of high-risked
      patients with CAS and could serve as a reference of communication when
      neurologists refer patients and before patients are treated by cardiologists.

PMID- 29060424
TI  - Combination of static and temporal data analysis to predict mortality and
      readmission in the intensive care.
AB  - There are approximately 4 million intensive care unit (ICU) admissions each year
      in the United States with costs accounting for 4.1% of national health
      expenditures. Unforeseen adverse events contribute disproportionately to these
      costs. Thus, there has been substantial research in developing clinical decision
      support systems to predict and improve ICU outcomes such as ICU mortality,
      prolonged length of stay, and ICU readmission. However, the data in the ICU is
      collected at diverse time intervals and includes both static and temporal data.
      Common methods for static data mining such as Cox and logistic regression and
      methods for temporal data analysis such as temporal association rule mining do
      not model the combination of both static and temporal data. This work aims to
      overcome this challenge to combine static models such as logistic regression and
      feedforward neural networks with temporal models such as conditional random
      fields(CRF). We demonstrate the results using adult patient records from a
      publicly available database called Multi-parameter Intelligent Monitoring in
      Intensive Care - II (MIMIC-II). We show that the combination models outperformed
      individual models of logistic regression, feed-forward neural networks and
      conditional random fields in predicting ICU mortality. The combination models
      also outperform the static models of logistic regression and feed-forward neural
      networks for the prediction of 30 day ICU readmissions when tested using Matthews
      correlation coefficient and accuracy as the metrics.

PMID- 29060425
TI  - Functional hemispheric asymmetry in female prefrontal hemodynamics corresponding
      to changes in auditory sense during pregnancy and child raising.
AB  - We carried out further research into the prefrontal hemodynamics corresponding to
      changes in a women's auditory sense during pregnancy and child raising. A total
      of forty-six volunteers took part in our experiment, and we divided them into
      several groups in accordance with the progress of their child raising. For the
      auditory tasks performed by the volunteers, we used two auditory stimulations:
      the sound of baby crying, and a classical music as a control. Hemodynamic changes
      at the prefrontal regions were measured using a 2 ch functional near-infrared
      spectroscopy (fNIRS) along with a 47 ch fNIRS instrument equipped with 3*5 probes
      (22 ch). Judging the results of the female groups about their prefrontal
      hemodynamics, there were almost no significant differences across the groups in
      the dynamics with the music task. However, in the section of the baby crying
      task, their hemodynamics were regarded as significant compared to the control.
      Concerning the time scale of the changes in the hemodynamic response to the two
      tasks, especially in the postnatal group, we took notice of the possibility that
      higher activations were clearly observed at the right sides of their brains than
      their left sides. Our experimental results not only demonstrated that postnatal
      women within one and a half years of their childbearing might have acute ears,
      but also revealed the hemispheric asymmetry in their prefrontal hemodynamics, as
      compared to pregnant and nonpregnant volunteers. We inferred that the pregnancy
      inducing expression of such women's special capabilities is definitely due to a
      boost-up of a built-in female disposition, which is destined for expressions of
      maternal love.

PMID- 29060426
TI  - Queue-based modelling and detection of parameters involved in stroke outcome.
AB  - We designed a queue-based model, and investigated which parameters are of
      importance when predicting stroke outcome. Medical record forms have been
      collected for 57 ischemic stroke patients, including medical history and vital
      sign measurement along with neurological scores for the first twenty-four hours
      of admission. The importance of each parameter is identified using multiple
      regression combined with a circular queue to iteratively fit outcome. Out of 39
      parameters, the model isolated 14 which combined could estimate outcome with a
      root mean square error of 1.69 on the Scandinavian Stroke Scale, where outcome
      for patients were 36.75 +/- 10.99. The queue-based model integrating multiple
      linear regression shows promising results for automatic selection of significant
      medically relevant parameters.

PMID- 29060427
TI  - Pattern discovery and similarity assessment for robust heart sound segmentation.
AB  - Heart Sound Segmentation plays a fundamental role in pathology detection in
      Phonocardiogram (PCG) signals. This matter of study has been widely studied in
      the past decades, however the majority of algorithms' results correspond only to
      small databases, composed by only quality signals or signals specific to one
      acquisition system. In this work we proposed a robust segmentation algorithm
      integrated with clinical information, based on a pattern recognition approach for
      segmentation of the fundamental heart sounds, which is validated in several
      databases from different countries and with different acquisition
      instrumentations. The database comprises a total of 3153 recordings from 764
      patients with a variety of pathological conditions. The general results were 95%
      and 96% of sensitivity and positive predictivity, respectively. Based on the
      results the algorithm is able to perform with accuracy maintaining generalization
      capabilities.

PMID- 29060428
TI  - The application of individual virtual nostalgic game design to the evaluation of
      cognitive function.
AB  - The aim of this study was to develop a task set based on personalized material
      for nostalgic experience, which could detect cognitive ability via a virtual
      experience system combined with Kinect somatosensory interactive operation
      applications without the user wearing any accessory input device. Fifty-nine
      subjects participated in the experiment. The receiver operating characteristic
      curve of the game system was statistically analyzed for determining the best
      cutoff-point in the cognitive function assessment. Correlation analysis and
      regression analysis were used to explore the correlations between the results and
      the clinical cognitive assessment scales. According to the MoCA scores, the
      results showed that the accuracy of the system was 86.4% in evaluating mild
      cognitive impairment. The system seems feasible and was strongly correlated with
      clinical cognitive assessment scales. We anticipate that daily use of our system
      could keep track of changes of cognitive function of the elderly in home life.

PMID- 29060429
TI  - Correlation of P300 ERPs with visual stimuli and its application to vigilance
      detection.
AB  - Vigilance or sustained attention is defined as the ability to maintain
      concentrated attention over prolonged time periods. It is an important aspect in
      industries such as aerospace and nuclear power, which involve tremendous man
      machine interaction and where safety of any component/system or environment as a
      whole is extremely crucial. Many methods for vigilance detection, based on
      biological and behavioral characteristics, have been proposed in the literature.
      Nevertheless, the existing methods are associated with high time complexity,
      unhandy devices and incur huge equipment overhead. This paper aims to pave an
      alternative solution to the existing techniques using brain computing interface
      (BCI). EEG device being a non-invasive BCI technique is popular in many
      applications. In this work, we have utilized P300 component of ERPs of EEG signal
      for vigilance detection task as it can be detected fast and accurately. Through
      this work, we aim to establish the correlation between P300 ERP and vigilance. We
      have performed a number of experiments to substantiate the correctness of our
      proposal and have also proposed an approach to measure the vigilance level.

PMID- 29060430
TI  - Concussion management application for amateur sports.
AB  - Concussion management has become one of the most popular topics in sports
      medicine. Significant resources are being invested in developing protocols for
      professional sport associations such as the NFL and FIFA. These protocols are
      often expensive and require substantial resources to implement. The problem,
      however, runs much deeper than just professional sports. Currently there exists
      little infrastructure to effectively manage concussion in amateur settings such
      as high school, club and university sport. A more holistic approach is required
      to ensure that the same standard of concussion management is being implemented
      across the board, regardless of the available medical and financial resources. An
      application was developed that will allow for easily accessible baseline testing
      and access to a player's concussion history from anywhere in the world. The
      application will be used to monitor players from the day they start playing sport
      until they potentially become professional sport players.

PMID- 29060431
TI  - Efficient implementation of Stockwell Transform for real-time embedded processing
      of physiologic signals.
AB  - Physiologic monitoring enables scientists and physicians to study both normal and
      pathologic signals of the body. While wearable technologies are available today,
      many of these technologies are limited to data collection only. Embedded
      processors have minimal computational capabilities. We propose an efficient
      implementation of the Stockwell Transform which can enable real-time time
      frequency analysis of biological signals in a microcontroller. The method is
      built upon the fact that the Stockwell Transform can be implemented as a compact
      filter bank with pre-computed filter taps. Additionally, due to the long tails of
      the gaussian windowing function, low amplitude filter taps can be removed. The
      method was implemented on a TI MSP430 processor. Simulated ECG data was fed into
      the processor to demonstrate performance and evaluate computational efficiency.

PMID- 29060432
TI  - APEX_SCOPE: A graphical user interface for visualization of multi-modal data in
      inter-disciplinary studies.
AB  - In multi-disciplinary studies, different forms of data are often collected for
      analysis. For example, APEX, a study on the automated prediction of extubation
      readiness in extremely preterm infants, collects clinical parameters and
      cardiorespiratory signals. A variety of cardiorespiratory metrics are computed
      from these signals and used to assign a cardiorespiratory pattern at each time.
      In such a situation, exploratory analysis requires a visualization tool capable
      of displaying these different types of acquired and computed signals in an
      integrated environment. Thus, we developed APEX_SCOPE, a graphical tool for the
      visualization of multi-modal data comprising cardiorespiratory signals, automated
      cardiorespiratory metrics, automated respiratory patterns, manually classified
      respiratory patterns, and manual annotations by clinicians during data
      acquisition. This MATLAB-based application provides a means for collaborators to
      view combinations of signals to promote discussion, generate hypotheses and
      develop features.

PMID- 29060433
TI  - CTG Analyzer: A graphical user interface for cardiotocography.
AB  - Cardiotocography (CTG) is the most commonly used test for establishing the good
      health of the fetus during pregnancy and labor. CTG consists in the recording of
      fetal heart rate (FHR; bpm) and maternal uterine contractions (UC; mmHg). FHR is
      characterized by baseline, baseline variability, tachycardia, bradycardia,
      acceleration and decelerations. Instead, UC signal is characterized by presence
      of contractions and contractions period. Such parameters are usually evaluated by
      visual inspection. However, visual analysis of CTG recordings has a well
      demonstrated poor reproducibility, due to the complexity of physiological
      phenomena affecting fetal heart rhythm and being related to clinician's
      experience. Computerized tools in support of clinicians represents a possible
      solution for improving correctness in CTG interpretation. This paper proposes CTG
      Analyzer as a graphical tool for automatic and objective analysis of CTG
      tracings. CTG Analyzer was developed under MATLAB(r); it is a very intuitive and
      user friendly graphical user interface. FHR time series and UC signal are
      represented one under the other, on a grid with reference lines, as usually done
      for CTG reports printed on paper. Colors help identification of FHR and UC
      features. Automatic analysis is based on some unchangeable features definitions
      provided by the FIGO guidelines, and other arbitrary settings whose default
      values can be changed by the user. Eventually, CTG Analyzer provides a report
      file listing all the quantitative results of the analysis. Thus, CTG Analyzer
      represents a potentially useful graphical tool for automatic and objective
      analysis of CTG tracings.

PMID- 29060434
TI  - A comparative study of electronic stethoscopes for cardiac auscultation.
AB  - There are several electronic stethoscopes available on the market today, with a
      very high potential for healthcare namely telemedicine, assisted decision and
      education. However, there are no recent comparatives studies published about the
      recording quality of auscultation sounds. In this study we aim to: a) define a
      ranking, according to experts opinion of 6 of the most relevant electronic
      stethoscopes on the market today; b) verify if there are any relations between a
      stethoscope's performance and the type of pathology present; c) analyze if some
      pathologies are more easily identified than others when using electronic
      auscultation. Our methodology consisted in creating two study groups: the first
      group included 18 cardiologists and cardiology house officers, acting as the gold
      standard of this work. The second included 30 medical students. Using a database
      of heart sounds recorded in real hospital environments, we applied questionnaires
      to observers from each group. The first group listened to 60 cardiac
      auscultations recorded by the 6 stethoscopes, and each one was asked to identify
      the pathological sound present: aortic stenosis, mitral regurgitation or normal.
      The second group was asked to choose, between two auscultation recordings, using
      as criteria the best sound quality for the identification of pathological sounds.
      Results include a total of 1080 evaluations, in which 72% of cases were correctly
      diagnosed. A detailed breakdown of these results is presented in this paper. As
      conclusions, results showed that the impact of the differences between
      stethoscopes is very small, given that we did not find statistically significant
      differences between all pairs of stethoscopes. Normal sounds showed to be easier
      to identify than pathological sounds, but we did not find differences between
      stethoscopes in this identification.

PMID- 29060435
TI  - Symptom-based data preprocessing for the detection of disease outbreak.
AB  - Early warning systems for outbreak detection is a challenge topic for researchers
      in the epidemiology and biomedical informatics fields. We are proposing a new
      method for detecting disease epidemics using a symptom-based approach. The data
      was collected from developed mobile applications which include users' demographic
      information and a list of chief complaint symptoms. Deliberated outbreaks are
      differentiated from seasonal outbreak by specific symptoms that represent a sign
      of infection. These symptoms were grouped, classified, and then converted to a
      time-series digital signal using the consensus scoring approach. Through the
      syndromic grouping method, the system digitized each data package into a single
      independent variable that is ready for further one-dimensional signal processing
      to predict disease outbreaks in the future.

PMID- 29060436
TI  - Predictive modeling to identify scheduled radiology appointments resulting in non
      attendance in a hospital setting.
AB  - No-show appointments are a troublesome, but frequent, occurrence in radiology
      hospital departments and private practice. Prior work in medical appointment no
      show prediction has focused on general practice and has not considered features
      specific to the radiology environment. We collect data from 16 years of
      outpatient examinations in a multi-site hospital radiology department. Data from
      the radiology information system (RIS) are fused with patient income estimated
      from U.S. Census data. Features were categorized into three groups: Patient,
      Exam, and Scheduling. Models based on the total feature set and separately on
      each feature group were developed using logistic regression to assess the per
      appointment likelihood of no-show. After five-fold cross-validation, no-show
      prediction using the total feature set from 554,611 appointments yielded an area
      under the curve (AUC) of 0.770 +/- 0.003. Feature groups that were most
      informative in the prediction of no-show appointments were those based on the
      type of exam and on scheduling attributes such as the lead time of scheduling the
      appointment. A data-driven no-show prediction model like the one presented here
      could be useful to schedulers in the implementation of an automated scheduling
      policy or the assignment of examinations with a high risk of no-show to lower
      impact appointment slots.

PMID- 29060437
TI  - New tele-diagnostic model using volume sweep imaging for rural areas.
AB  - Advances in information and communications technologies provide a new opportunity
      to improve the access to healthcare in remote rural areas (RA) where there is a
      lack of infrastructure and medical experts. This paper implements a new model for
      tele-ultrasound (US) based on volumetric sweep imaging protocols specially
      designed for the acquisition of US. Non-physician health personnel from the RA
      are trained on the use of these protocols in a few days. The operator utilizes
      the medical box (MB), a specially designed telecommunication system, to guide,
      compress, encrypt and transmit the US sweeps through the cloud to the radiologist
      who performs the diagnosis remotely. The report is automatically sent back to the
      MB. The system was able to send US volumetric images with poor connectivity
      conditions in 6 minutes on average. These results of implementing this tele
      ultrasound model in RAs are encouraging and support future validations.

PMID- 29060438
TI  - Exploratory multivariate analysis of hospital admissions data in conjunction with
      workforce data.
AB  - The prevalence of electronic health data has brought us a step closer to
      understanding of the dynamics of hospital admissions. However, little research
      has investigated hospital admission data in conjunction with information about
      the environment where the patient was admitted, such as staffing level and
      hospital type. This paper studied this crucial but often neglected issue by
      investigating hospital admission records together with workforce data.
      Exploratory multivariate analysis methods, such as principal component analysis
      (PCA) and multiple correspondence analysis (MCA), were applied to study important
      variables associated with admission and workforce data. The exploratory results
      obtained shed light on the contribution of these variables to the typology of
      hospital admissions.

PMID- 29060439
TI  - Design of an mHealth System for Maternal and Children HIV care.
AB  - While progress has been made to slow down its spread and increase uptake of
      treatment, human immunodeficiency virus infection and acquired immune deficiency
      syndrome (HIV/AIDS) is still a highly significant health problem for many low-
      and middle-income countries (LMICs). Specifically, almost half of new HIV
      patients in Asia Pacific were children. The prevention of mother-to-child
      transmission faces complex socioeconomic and other problems. With the increasing
      growth of mobile technologies in LMICs, especially in Asia Pacific, mHealth, the
      application of mobile technology for health applications, has a significant
      potential to help alleviate these problems. In this paper, we propose the design
      of an mHealth System for Maternal and Children HIV care. It includes specialized
      portals for patients, family/community members, healthcare providers, healthcare
      referral system, payers and drug supply chain. While each portal is customized
      towards the needs of a particular actor, such as treatment scheduling and
      education for patients, and epidemiological data management for healthcare
      referrals, all the different elements are integrated through a central server to
      form an integrated system with a secured data exchange environment. This proposed
      integrative design is aimed to facilitate efficient, timely and coordinated
      information dissemination, analysis, and care across the healthcare system, and
      is intended for application in developing countries, especially in the Asia
      Pacific region.

PMID- 29060440
TI  - Modelling and analysis of four telemedicine Italian experiences.
AB  - In the last 10 years the European population aged 65 years and over grew of 2.3%,
      with Italy having the highest share of elderly persons in the total population.
      OPLON (OPportunities for active and healthy LONgevity) is a project supported by
      the Italian Ministry of Education, Universities, and Research aiming to identify
      and prevent frailty and to improve the life quality of elderly subjects. The main
      goal of OPLON is to develop a "Care&Cure" model for the management of subjects
      with different morbidities and co-morbidities, adaptable to the subject's risk
      level and to the regional contexts. In this study we analyzed four Italian
      telemedicine experiences addressed to chronic, geriatric or partially self
      sufficient subjects. Each of them was exhaustively described by means of three
      process modelling tools (synopsis, workflow and swimlane activity diagrams).
      Starting from this analysis, we defined a general model of tele-monitoring and
      tele-assistance of frail and pre-frail people with different needs and
      pathologies. The proposed model was characterized by three macro processes
      (enrollment, assessment and assistance) and four groups of actors (patient,
      general practitioner/specialist physician, multidisciplinary team, and healthcare
      professionals). Combining this model with a detailed analysis of regulations and
      legislations in force both at local and national level, it will be possible to
      design the complete and efficient "Care&Cure" model.

PMID- 29060441
TI  - Towards objective and reproducible study of patient-doctor interaction: Automatic
      text analysis based VR-CoDES annotation of consultation transcripts.
AB  - While increasingly appreciated for its importance, the interaction between health
      care professionals (HCP) and patients is notoriously difficult to study, with
      both methodological and practical challenges. The former has been addressed by
      the so-called Verona coding definitions of emotional sequences (VR-CoDES) - a
      system for identifying and coding patient emotions and the corresponding HCP
      responses - shown to be reliable and informative in a number of independent
      studies in different health care delivery contexts. In the preset work we focus
      on the practical challenge of the scalability of this coding system, namely on
      making it easily usable more widely and on applying it on larger patient cohorts.
      In particular, VR-CoDES is inherently complex and training is required to ensure
      consistent annotation of audio recordings or textual transcripts of
      consultations. Following up on our previous pilot investigation, in the the
      present paper we describe the first automatic, computer based algorithm capable
      of providing coarse level coding of textual transcripts. We investigate different
      representations of patient utterances and classification methodologies, and label
      each utterance as either containing an explicit expression of emotional distress
      (a 'concern'), an implicit one (a 'cue'), or neither. Using a data corpus
      comprising 200 consultations between radiotherapists and adult female breast
      cancer patients we demonstrate excellent labelling performance.

PMID- 29060442
TI  - An ordinal classification approach for CTG categorization.
AB  - Evaluation of cardiotocogram (CTG) is a standard approach employed during
      pregnancy and delivery. But, its interpretation requires high level expertise to
      decide whether the recording is Normal, Suspicious or Pathological. Therefore, a
      number of attempts have been carried out over the past three decades for
      development automated sophisticated systems. These systems are usually
      (multiclass) classification systems that assign a category to the respective CTG.
      However most of these systems usually do not take into consideration the natural
      ordering of the categories associated with CTG recordings. In this work, an
      algorithm that explicitly takes into consideration the ordering of CTG
      categories, based on binary decomposition method, is investigated. Achieved
      results, using as a base classifier the C4.5 decision tree classifier, prove that
      the ordinal classification approach is marginally better than the traditional
      multiclass classification approach, which utilizes the standard C4.5 algorithm
      for several performance criteria.

PMID- 29060443
TI  - An interpretable data-driven approach for rules construction: Application to
      cardiovascular risk assessment.
AB  - The development of models able to produce an understandable decision by the
      clinicians is of great importance to support their decision. Therefore, the
      research of methodologies able to extract useful knowledge from existing
      datasets, as well as to integrate this knowledge into the current clinical
      evidence, is a key aspect in the enhancement of the clinical decision. This work
      focuses on the development of interpretable models to assess the patient's
      condition based on supervised clustering theories, enabling the discovery of a
      set of features that best represents that condition. At the same time, the
      technique is supported on a structure that enables the formulation of simple and
      interpretable rules. Despite its general applicability, the proposed methodology
      is applied to coronary artery disease (CAD), particularly, in the risk of death
      assessment (30 days after the admission) of patients that have been admitted to
      the emergency unit. The validation is performed using a real dataset with Acute
      Coronary Syndromes, provided by the Portuguese Society of Cardiology. While the
      methodology produces simple and interpretable rules, the performance achieves an
      improvement of 7% in relation to geometric mean, when compared with GRACE model
      (commonly used in Portugal).

PMID- 29060444
TI  - Classification models to predict vasopressor administration for septic shock in
      the emergency department.
AB  - Optimal management of sepsis and septic shock in the emergency department (ED)
      involves timely decisions related to intravenous fluid resuscitation and
      initiation of vasoactive medication support. A decision-support tool trained on
      electronic health record data, can help improve this complex decision. We
      retrospectively extracted vital signs, lab measurements, and fluid administration
      information from 807 patient visits over a two-year period to a major ED.
      Patients selected for inclusion had a high likelihood of septic shock. We trained
      binary classifiers to discriminate between patients administered vasopressors in
      the ED and those not administered vasopressors at any point. Using features
      extracted from the entire ED visit record yielded a maximum area under the
      receiver-operating characteristic curve (AUC) of 0.798 (95% CI 0.725-0.849) in a
      hold-out test set. In a separate task, we used individual vital signs
      observations with lab results to predict vasopressor administration, yielding a
      maximum AUC of 0.762 (95% CI 0.748-0.777). Lastly, we trained separate
      classifiers for different subgroups of vital signs observations. These subgroups
      were defined by the cumulative number of fluid boluses delivered at the time of
      the observation. The maximum AUC achieved by any of these classifiers was 0.815
      (95% CI 0.784-0.853), occurring for vital signs observations made after 2 bolus
      administrations. Classifiers in all tasks significantly outperformed existing
      clinical tools for assessing prognosis in ED sepsis. This work shows how
      relatively few features can provide instantaneous and accurate prediction of need
      for an intervention that is typically a complex clinical decision.

PMID- 29060445
TI  - Reconciliation of SNOMED CT and domain clinical model for interoperable medical
      knowledge creation.
AB  - Use of heterogeneous data models in hospital information systems (HIS), obstructs
      the integration of clinical decision support system (CDSS) with clinical
      workflows. The diverse concepts diminish the interoperability level among the
      CDSS knowledge bases and data models of HIS. Standard terminology utilization in
      knowledge acquisition and its reconciliation with HIS data models are the
      candidate solution to overcome the interoperability barrier. We propose a
      reconciliation model to map concepts of diverse domain clinical models (DCM) with
      the standard terminology. In the proposed model, the implicit and explicit
      semantics are complemented to the word set of the targeted DCM concepts. The
      inclusion of semantics, mapped the DCM concepts to the SNOMED CT concepts with
      high accuracy. The results showed that the system correctly mapped 95% of
      concepts of DCM with standard terminology SNOMED CT concepts.

PMID- 29060446
TI  - Design and development of a customizable telemedicine platform for improving
      access to healthcare for underserved populations.
AB  - Telemedicine offers a method to bridge the healthcare access gap in low and
      middle income countries (LMICs) by connecting providers with patients using
      appropriate technology. Here we describe the design and development of a novel
      modular telemedicine platform, Intelehealth, that would enable health systems to
      connect remote doctors with patients in rural clinics using a customizable
      Android-based platform and a cloud-based electronic health record system at the
      backend (OpenMRS). This open source platform enables task shifting of medically
      relevant information gathering by a local health worker, transmission of this
      information to a remote doctor, and a telephonic conversation between the doctor
      and the patient that subsequently allows for delivery of an appropriate
      therapeutic plan. Intelehealth is designed to operate on a low bandwidth internet
      environment, and will be tested and validated in rural health clinics in India.

PMID- 29060447
TI  - Wireless gyroscope platform enabled by a portable media device for quantifying
      wobble board therapy.
AB  - The wobble board enables a therapy strategy for rehabilitation of the ankle foot
      complex. Quantification of therapy, such as through the use of a wobble board,
      can facilitate a therapist's acuity for advancing and optimizing the overall
      therapy strategy. The portable media device, such as an iPod, can be equipped
      with a software application to function as a wireless gyroscope platform.
      Integration of the wobble board with the portable media device functioning as a
      wireless gyroscope enables the potential for patient to therapist interaction
      through connectivity to the Internet. A patient can conduct wobble board therapy
      for the ankle foot complex from the convenient vantage point of a homebound
      setting with therapy data transmitted wirelessly as email attachments. The
      gyroscope signal of the wobble board therapy can be consolidated into a feature
      set for machine learning classification. Using a multilayer perceptron neural
      network considerable classification accuracy has been achieved for
      differentiating between a hemiplegic affected ankle and unaffected ankle while
      using a wobble board. The combination of machine learning, wireless systems, such
      as a portable media device functioning as a wireless gyroscope, and a
      conventional therapy device, such as a wobble board, are envisioned to advance
      the capability to optimally impact the rehabilitation experience.

PMID- 29060448
TI  - Improving the accuracy of existing camera based fall detection algorithms through
      late fusion.
AB  - Fall incidents remain an important health hazard for older adults. Fall detection
      systems can reduce the consequences of a fall incident by insuring that timely
      aid is given. Currently fall detection algorithms however suffer a reduction in
      accuracy when introduced in real-life situations. In this paper a late fusion
      technique is proposed that will improve the accuracy of existing fall detection
      systems. It combines the confidence levels of different single camera fall
      detection systems. Four different aggregation methods are compared to each other
      based on the Area Under the Curve (AUC) of precision-recall curves. Calculating
      the median of the confidence levels of five cameras an increase of 218% in the
      AUC of the precision-recall-curves is achieved compared to the AUC of the single
      camera fall detector. These results show that significant improvements can be
      made to the accuracy of single camera fall detectors in a relatively easy way.

PMID- 29060449
TI  - An integrated system for the monitoring of therapy and drug's side effects in
      Lymphoproliferative disorders.
AB  - The wide diffusion of telecommunication systems and the availability of cheap
      computational devices, such as smart wearable, PDA and smartphones, is
      multiplying the number of collaborative and remote-monitored applications
      accessible to a large mass of people. In particular, this scenario makes it
      possible the implementation of specific systems that improve the control of
      patients with minimal impact on the quality of their lives. This paper moves in
      this context and presents a general system for the continuous monitoring at home
      of therapy and disease symptoms. Indeed, starting from a specific application
      aiming at monitoring patients with Lymphoproliferative disorders and the side
      effects related to specific drugs used in treatment of these diseases, in this
      paper we present a more general framework easy customizable to the requirements
      of different applications. In particular, the proposed system has been designed
      to be easily tuned to a larger class of disorders and, in our opinion, it can be
      applied in almost all the scenarios where patients require a strict monitoring of
      their conditions in their home environment. The paper presents the model, the
      architecture and the implementation of the system.

PMID- 29060450
TI  - Real-time WebRTC-based design for a telepresence wheelchair.
AB  - This paper presents a novel approach to the telepresence wheelchair system which
      is capable of real-time video communication and remote interaction. The
      investigation of this emerging technology aims at providing a low-cost and
      efficient way for assisted-living of people with disabilities. The proposed
      system has been designed and developed by deploying the JavaScript with Hyper
      Text Markup Language 5 (HTML5) and Web Real-time Communication (WebRTC) in which
      the adaptive rate control algorithm for video transmission is invoked. We
      conducted experiments in real-world environments, and the wheelchair was
      controlled from a distance using the Internet browser to compare with existing
      methods. The results show that the adaptively encoded video streaming rate
      matches the available bandwidth. The video streaming is high-quality with
      approximately 30 frames per second (fps) and round trip time less than 20
      milliseconds (ms). These performance results confirm that the WebRTC approach is
      a potential method for developing a telepresence wheelchair system.

PMID- 29060452
TI  - Tracking of non-dividing cells by using generalized Voronoi diagram.
AB  - Cell tracking is an important technique to study cell migration. However, to
      obtain good tracking results is still a challenging task. False positives and
      false negatives are two main factors that affect cell tracking accuracy. It is
      desirable to have a good method to eliminate false positives and false negatives
      effectively. We propose to use generalized Voronoi diagrams (GVDs) to perform
      tracking for non-dividing cells in a key point evolving based algorithm. This
      method can realize tracking association for multiple objects based cell racking
      and eliminate false positives and false negatives effectively based on a defined
      cost function. We investigated under what conditions our algorithm would work,
      and what were the results when the assumptions for the algorithm were violated.
      This provides the relationship between the cell migration speed and movie
      temporal resolution. We further validated that our algorithm works well under
      reasonable assumptions. We tested our algorithm with both 2D+time and 3D+time
      data sets. In conclusion, the use of Generalized Voronoi Diagram in cell tracking
      is an effective technique to increase tracking accuracy. The temporal resolution
      when acquiring movies should be ensured in order to achieve good tracking
      results.

PMID- 29060451
TI  - Model evaluation-based approaches for endothelial function.
AB  - In order to develop an evaluation method for the endothelial function from blood
      flow information, a mathematical model and simulation technique that can
      simultaneously analyze hemodynamics and vessel wall dynamics were proposed.
      Experimental observations reveal that the proposed method adequately reproduced
      blood flow data. There was also confirmation that the method enables access of
      the internal state of the blood vessels, which is difficult to measure directly.

PMID- 29060453
TI  - A mathematical model of the effects of anoctamin-1 loss on intestinal slow wave
      entrainment.
AB  - The interstitial cells of Cajal (ICC) generate electrophysiological events called
      slow waves that regulate the motility of the gastrointestinal (GI) tract. Recent
      studies have demonstrated that the Ca2+-activated Cl- -channel, encoded by the
      anoctamin1 (Ano1) protein, has a major role in regulating intestinal slow waves
      and motility. The main aim of this study was to develop a multi-scale
      mathematical model capable of simulating both normal slow wave entrainment and
      the effects of Ano1 knockout (KO) on the normal activity. A biophysically-based
      cell model was adapted to simulate the effects of Ano1 KO at the cellular level.
      A 10mm one-dimensional (1D) model was then developed to simulate entrained
      intestinal slow wave propagation. Cellular KO at levels of 100% and 20% were
      applied to a varying-sized middle region of the 1D model. The main finding was
      that the level of loss of entrainment increased as both cellular and spatial Ano1
      KO levels increased, mostly manifesting as ectopic activation. In the future,
      this model will be extended and used in combination with Ca2+ -imaging data to
      quantitatively investigate the effects of Ano1 loss in ICC.

PMID- 29060454
TI  - A computational model of intracellular calcium oscillations in urinary bladder
      smooth muscle cells.
AB  - This paper presents a computational model for calcium (Ca2+) oscillations in
      detrusor smooth muscle (DSM) cells. The proposed model simulates the temporal
      profile of oscillations by incorporating various cellular and subcellular
      components. The cellular components include calcium influx via membrane and the
      plasma membrane calcium ATPase (PMCA) pump. The subcellular components include
      ryanodine receptors (RyRs), inositol 1, 4, 5 trisphosphate receptors (IP3Rs) and
      the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump. The use of both
      cellular and subcellular components provides a better estimation of the origin
      and factors affecting these oscillations. Moreover, our work correlates these
      computational findings with associated physiology of the smooth muscle cell that
      aids our understanding of intracellular calcium oscillations and its inception in
      DSM. A deeper insight into calcium signalling in DSM cells is expected to provide
      a firmer basis for understanding the mechanical contractile activity.

PMID- 29060455
TI  - A computational study of the role of mitochondrial organization on cardiac
      bioenergetics.
AB  - All cells in the body have a specific shape and internal organization which is
      specific to that cell's function. Heart cells are rod-shaped, and contain arrays
      of contractile protines (myofibrils) and mitochondria (organelles that produce
      energy) that are aligned along the length of the rod. This arrangement is
      presumed to allow the cell to generate maximal contractile force for each
      heartbeat and for energy metabolites to be readily available to generate this
      force. Heart disease phenotypes, such as diabetic cardiomyopathy and heart
      failure, exhibit altered organization of mitochondria. However, physiological and
      computational studies have predominantly investigated the effect of the
      biochemical changes that accompany the disease alone, such as reduced rates of
      ATP production by mitochondria. We present a modeling study that examines the
      effect of mitochondrial organization on energy metabolite distribution during the
      heartbeat. A 2D micrograph of the cell cross-section was selected from a 3D image
      stack of structural data of a cardiac cell. The image was used to generate a 2D
      finite element model, on which mitochondrial oxidative phosphorylation and energy
      metabolite diffusion was modelled. Results illustrate that mitochondrial density
      can induce heterogeneity in the distribution of metabolites across the cell area.
      We discuss the implications of these findings and avenues for future, more
      indepth studies.

PMID- 29060456
TI  - Cell dynamic morphology analysis by deep convolutional features.
AB  - Computational analysis of cell dynamic morphology in time-lapse image is a
      challenging task in biomedical research. Inspired by the recent success of deep
      learning, we investigate the possibility to apply a deep neural network to cell
      dynamic morphology analysis in this paper. Specifically, a contour spectrum is
      composed as the input of neural network to characterize cell spatiotemporal
      deformation, then a pre-trained convolutional neural network model is performed
      for automatic feature extraction. Finally, the extracted deep convolutional
      features are analyzed by SVM. Experimental results demonstrate that the proposed
      strategy outperforms existing methods on the live-cell database, and the features
      extracted by the last layer and classified by linear kernel SVM allows for the
      state-of-the-art performance.

PMID- 29060457
TI  - A pharmacokinetic model of drug-drug interaction between clopidogrel and
      omeprazole at CYP2C19 in humans.
AB  - BACKGROUND: Clopidogrel is a thienopryridine antiplatelet agent commonly used in
      the management of cardiovascular diseases. Clopidogrel is metabolized by hepatic
      CYP2C19 and CYP2B6, therefore, co-administration of clopidogrel and CYP2C19
      inhibitors can alter pharmacokinetics of clopidogrel. Omeprazole is a proton pump
      inhibitor used for decreasing gastric acid production. Omeprazole is known to be
      a potent inhibitor of CYP2C19. Thus when the drugs are simultaneously
      administered, clopidogrel plasma concentration levels can be increased. However,
      plasma levels of the active metabolite of clopidogrel can be significantly
      decreased, thereby, its antiplatelet activity is reduced. OBJECTIVES: We aimed to
      develop a mathematical model describing a drug-drug interaction between
      clopidogrel and omeprazole in humans. METHODS: Searching for pharmacokinetic
      interaction studies between clopidogrel and omeprazole in humans was performed in
      PubMed. Six studies were selected into our modeling purposes to develop 3
      mathematical models (i.e. 4 studies for clopidogrel alone, 1 study for omeprazole
      alone and 1 study for clopidogrel-omeprazole interaction). Subsequently,
      concentration-time course data from the selected studies were extracted. Computer
      codes and simulations were performed using the Advanced Continuous Simulating
      Language Extreme (ACSLX) program. RESULTS: We successfully developed 3
      mathematical models which are able to describe all of the datasets. CONCLUSIONS:
      Our clopidogrel-omeprazole pharmacokinetic interaction model with a description
      of competitive inhibition at CYP2C19 could successfully describe concentration
      time courses from the selected datasets. Our interaction model may be useful in
      predicting plasma levels of clopidogrel and its active metabolite.

PMID- 29060458
TI  - Improved microRNA biomarkers for pathological stages in lung adenocarcinoma via
      clustering of dysregulated microRNA-target associations.
AB  - Most of cancer-related deaths are due to lung cancer, and there is a need for
      reliable prognosis biomarkers to predict stages in lung adenocarcinoma cases.
      Recently, microRNAs are found to have potential as both biomarkers and
      therapeutic targets for lung cancer. As evidence suggests microRNA dysregulations
      are implicated in many cancer malignancies, it is important to consider the
      changes in miRNA-target associations among different lung cancer biological
      states. We proposed a novel clustering strategy to identify groups of miRNAs with
      similar dysregulated targets. Then, we incorporated the learned clusters of miRNA
      as prior knowledge to a Sparse Group Lasso classifier to improve classification
      results, thereby leading to more relevant selection of microRNA biomarkers. We
      apply the method to the TCGA Lung Adenocarcinoma dataset. In cross-validation
      tests, the AUC rate for each stages is 1.0, 0.71, 0.68, 0.64, and 0.90 for
      normal, Stage I, Stage II, Stage III, and Stage IV, respectively. Among the
      candidate miRNAs selected in the model, 87% are reported to be related to Lung
      Adenocarcinoma. Further result demonstrates that clustering miRNAs by considering
      the dysregulation between miRNAs and mRNA targets leads to biomarkers with higher
      precision and recall rate to known lung adenocarcinoma miRNAs.

PMID- 29060459
TI  - Multi-scale immunological and biomechanical model of emphysema progression.
AB  - This work presents a multi-scale agent-based model of emphysema progression that
      includes both the slow action of the immune system and the fast action of force
      redistribution and fracture propagation of the biological tissue. The two scales
      are coupled because the immune response causes inflammation and adaptation, which
      affects the biomechanical parameters of the tissue such as his elasticity. During
      repeated inflammation and breathing cycles, the tissue weakens and breaks down.
      We found that macrophages lifespan and cytokynes diffusion ratio are the
      parameters that influence the outcome of the model the most.

PMID- 29060460
TI  - A continuum model of electrical stimulation of multi-compartmental retinal
      ganglion cells.
AB  - A continuum multi-domain model of electrical stimulation of the retina is
      presented. Each point in the retinal ganglion cell layer could be thought of as
      representing a single cell, whose biophysics is described using a four
      compartment formulation incorporating varying ion channel expressions in the
      soma, axon initial segment, dendrites and axon. Our continuum model was validated
      against a discrete morphologically-realistic OFF RGC model, using intra- and
      extra-cellular electrical stimulation scenarios. Simulations from the continuum
      model reproduced the same results as that of the discrete model. Our continuum
      model is the first multi-domain model to represent all main RGC compartments, not
      just the soma. Moreover, we demonstrated that this model allows the investigation
      of axonal activation which has been observed to influence the perception of
      phosphenes.

PMID- 29060461
TI  - In silico investigation of the effects of hemolysis on the hyperspectral
      absorptance of blood in motion.
AB  - Measurement of the optical absorptance of blood can provide insight into its
      composition and behaviour. Accordingly, optical devices and sensors are commonly
      used in a clinical setting to measure the absorptance of blood, either directly
      or indirectly through measurement of skin spectral responses. These measurements
      enable the evaluation or constant monitoring of a patient's blood. In this paper,
      we perform predictive simulations to investigate the absorptance of blood and how
      it is affected by hemolysis. These simulations are performed using a cell-based
      light interaction model, known as CLBlood, which accounts for the orientation and
      distribution of red blood cells. This allows us to evaluate the effect of
      hemolysis under different flow conditions. Furthermore, we produce results in the
      ultraviolet, visible and infrared domains using CLBlood's hyperspectral
      capabilities. We then evaluate the sensitivity of the absorptance signature of
      blood to hemolysis in each of these domains under several experimental
      conditions. The observations in this paper enhance our understanding of the
      impact of hemolysis on the optical absorptance of blood, potentially leading to
      simplified and more accurate methods for its detection and monitoring.

PMID- 29060462
TI  - A physiologically-based pharmacokinetic model of methotrexate incorporating
      hepatic excretion via multidrug-resistance-associated protein 2 (Mrp2) in mice,
      rats, dogs, and humans.
AB  - An updated physiologically-based pharmacokinetic (PBPK) model of methotrexate
      (MTX) was built based on an earlier model developed by Bischoff et al. (1971).
      MTX has been known to be a substrate of multidrug-resistance-associated protein 2
      (Mrp2). A three-dimensional quantitative structure-activity relationship model
      (3D-QSAR) of Mrp2 was developed by Hirono et al. (2005). In our updated PBPK
      model of MTX, using the computational chemistry-derived binding affinity (Km), a
      Mrp2-mediated biliary excretion process was incorporated as the MTX excretory
      pathway. Our model simulation results are consistent with numerous datasets
      obtained from mice, rats, dogs, and humans, at a variety of dose levels.
      Comparisons were made between our updated PBPK model and the earlier one from
      Bischoff et al. using a PBPK Index approach. Our new PBPK model was further
      verified against additional pharmacokinetic datasets from rats under special
      experimental conditions (cannulated bile duct) and Eisai hyperbirilubinemic rats.

PMID- 29060463
TI  - Development of a physiologically based pharmacokinetic model of paraquat.
AB  - Paraquat (N, N'-dimethyl-4,4'-bipyridium dichloride) is a potent and widely used
      herbicide in agricultural countries, including Thailand. The presence of this
      chemical in the body can lead to toxic effects in the liver, kidney, and lung.
      Pulmonary toxicity has been identified as the main cause of acute toxicity in
      animals and humans. Chronic exposure to paraquat is associated with Parkinson's
      disease in humans. Paraquat is transported into the lungs by neutral amino acid
      transporter. Therefore, a physiologically based pharmacokinetic (PBPK) model of
      paraquat was developed with a description of the protein transporter mechanism.
      To develop a PBPK model of paraquat, a pharmacokinetic study of paraquat in rats
      was selected from the ThaiLIS and Pubmed database. The selected study contained
      tissue-specific concentration-time course information such as paraquat
      concentration levels in liver, kidney and lung. Physiologic parameters were
      acquired from the literature or determined using a Markov-Chain Monte Carlo
      (MCMC) technique. The developed PBPK model consisted of 5 organ compartments
      (i.e. kidney, liver, slowly perfused organs, richly perfuse organs and lung),
      featuring an incorporation of neutral amino acid transporter in the lung. Our
      model simulations could explain the data from the literature and adequately
      describe pharmacokinetics of paraquat in the rats. This developed PBPK model may
      be able help in understanding of paraquat-induced Parkinson's disease as well as
      in risk assessment of paraquat.

PMID- 29060464
TI  - ActiveMotif: Interactive motif discovery with human feedback.
AB  - Motif detection, which is to discover short patterns involved in many important
      biological processes, has been recently raised as an important task in
      bioinformatics. The traditional algorithms to find a sequence motif have been
      developed using machine learning only without involving the experience and domain
      knowledge of human experts effectively. In this paper, we propose an interactive
      motif discovery system by introducing a new learning algorithm, by generalizing a
      well-known statistical motif model, whose inference can be shepherded by human
      feedback.

PMID- 29060465
TI  - An in silico method to predict net calcium transfer during hemodialysis.
AB  - International guidelines for chronic hemodialysis patients suggest a dialysate
      calcium concentration between 1.25 and 1.5 mmol/L. However, it is not certain if
      these dialysate calcium levels result in net calcium transfer into the patient.
      With ubiquitous prevalence of vascular calcification in hemodialysis patients, it
      is pertinent to model the mass balance of calcium during dialysis. To this end,
      we developed a two compartmental patient model and spatiotemporal representation
      of dialyzer model to investigate and quantify the calcium mass balance during
      dialysis. The model accounts for calcium-albumin binding and varying protein
      concentration; the latter accounts for the Gibbs-Donnan effect. The model
      simulations suggest that despite a lower dialysate calcium concentration of 1.25
      mmol/L, some of our patients may be loaded with calcium during dialysis. This net
      calcium flux from dialysate to blood side may be a potential contributor to
      vascular calcification, a primary cause of cardiovascular mortality in
      hemodialysis patients.

PMID- 29060466
TI  - Remote monitoring, distress detection by slightest invasive systems: Sound
      recognition based on hierarchical i-vectors.
AB  - Europe has a growing aging population, leading to the need for adapted healthcare
      services. Our work aims at proposing a solution for falls detection of elderly
      people using sound recognition based on a hierarchical i-vectors system. The
      system presented in this paper improves significantly the accuracy of sound
      recognition compared to the state of the art methods. The latter provides a good
      recognition rate of 81.98% on noiseless sounds. This system needs to be tested in
      a noisy environment and this can be improved by using new sound descriptors.

PMID- 29060467
TI  - An anchored dynamic time-warping for alignment and comparison of swallowing
      acoustic signals.
AB  - Properties of signals captured by contact accelerometers assist the evaluation of
      human organs involved in the swallowing process. Here we present a novel method
      to account the alignment between two different swallowing signals based on two
      steps: first, a scaled cross-correlation determines an anchor point of maximum
      similarity between the signals, dividing both signals in two parts; next, dynamic
      time warping aligns the left and right parts of both signals. Additional
      filtering procedures are used smooth the swallowing signals due to their low SNR.
      The results show that this technique can be used to assess similarities between
      liquid and solid boluses of a subject.

PMID- 29060468
TI  - Analysis of phonocardiogram signals through proactive denoising using novel self
      discriminant learner.
AB  - Phonocardiogram (PCG) records heart sound and murmurs, which contains significant
      information of cardiac health. Analysis of PCG signal has the potential to detect
      abnormal cardiac condition. However, the presence of noise and motion artifacts
      in PCG hinders the accuracy of clinical event detection. Thus, noise detection
      and elimination are crucial to ensure accurate clinical analysis. In this paper,
      we present a robust denoising technique, Proclean that precisely detects the
      noisy PCG signal through pattern recognition, and statistical learning. We
      propose a novel self-discriminant learner that ensures to obtain distinct feature
      set to distinguish clean and noisy PCG signals without human-in-loop. We
      demonstrate that our proposed denoising leads to higher accuracy in subsequent
      clinical analytics for medical investigation. Our extensive experimentations with
      publicly available MIT-Physionet datasets show that we achieve more than 85%
      accuracy for noisy PCG signal detection. Further, we establish that physiological
      abnormality detection improves by more than 20%, when our proposed denoising
      mechanism is applied.

PMID- 29060470
TI  - Detection of explosive cough events in audio recordings by internal sound
      analysis.
AB  - We present a new method for the discrimination of explosive cough events, which
      is based on a combination of spectral content descriptors and pitch-related
      features. After the removal of near-silent segments, a vector of event boundaries
      is obtained and a proposed set of 9 features is extracted for each event. Two
      data sets, recorded using electronic stethoscopes and comprising a total of 46
      healthy subjects and 13 patients, were employed to evaluate the method. The
      proposed feature set is compared to three other sets of descriptors: a baseline,
      a combination of both sets, and an automatic selection of the best 10 features
      from both sets. The combined feature set yields good results on the cross
      validated database, attaining a sensitivity of 92.3+/-2.3% and a specificity of
      84.7+/-3.3%. Besides, this feature set seems to generalize well when it is
      trained on a small data set of patients, with a variety of respiratory and
      cardiovascular diseases, and tested on a bigger data set of mostly healthy
      subjects: a sensitivity of 93.4% and a specificity of 83.4% are achieved in those
      conditions. These results demonstrate that complementing the proposed feature set
      with a baseline set is a promising approach.

PMID- 29060469
TI  - A multichannel acoustic approach to define a pulmonary pathology as combined
      pulmonary fibrosis and emphysema syndrome.
AB  - Interstitial lung diseases (ILDs) have been increasing their relevance in loss of
      lives according to a recent world wide medical information. Idiopathic pulmonary
      fibrosis (IPF) and combined pulmonary fibrosis and emphysema syndrome (CPFES)
      belong to ILD class with the latter having a limited survival prognosis. In
      clinical environment high resolution computed tomography (HRCT) is used to detect
      CPFE; however, there is still controversy about the amount of emphysema observed
      in HRCT to declare CPFES. Consequently, to help in the diagnosis of CPFES to
      develop an alternative technique seems to be attractive. In this study, we
      propose a multichannel acoustic approach to discriminate between IPF and CPFES
      parameterizing the multichannel lung sounds information linearly and classifying
      it by neural networks (NN). The NN performance using different features provided
      values above 90% in the validation phase. Furthermore, to test the trained NN,
      the proposed approach was applied on new data from five patients 3 diagnosed by
      experts as CPFES and 2 with IPF. The univariate autoregressive model obtained the
      best classification followed by the feature vector formed by the percentile
      frequencies augmented by the total power of the acoustic information. Results
      indicate that multichannel acoustic analysis is promising to discern between
      these two ILDs.

PMID- 29060471
TI  - Kernel-based adaptive learning improves accuracy of glucose predictive modelling
      in type 1 diabetes: A proof-of-concept study.
AB  - This study aims at demonstrating the need for nonlinear recursive models to the
      identification and prediction of the dynamic glucose system in type 1 diabetes.
      Nonlinear regression is performed in a reproducing kernel Hilbert space, by the
      Approximate Linear Dependency Kernel Recursive Least Squares (KRLS-ALD)
      algorithm, such that a sparse model structure is accomplished. The method is
      evaluated on seven people with type 1 diabetes in free-living conditions, where a
      change in glycaemic dynamics is forced by increasing the level of physical
      activity in the middle of the observational period. The univariate input allows
      for short-term (<=30 min) predictions with KRLS-ALD reaching an average root mean
      square error of 15.22+/-5.95 mgdL-1 and an average time lag of 17.14+/-2.67 min
      for an horizon of 30 min. Its performance is considerably better than that of
      time-invariant (regularized) linear regression models.

PMID- 29060472
TI  - Suppression of ventilation artifacts for gastrointestinal slow wave recordings.
AB  - Gastrointestinal extracellular slow wave recordings are providing critical
      information about normal motility and pathophysiology of the gut. Processing the
      signals is an important adjunct to acquire clinically and physiologically
      meaningful analysis. In stomach and intestine in vivo slow wave recordings,
      ventilation (or respiratory) artifacts can be prominent, which hinders
      identification and analysis of slow wave profiles. Here, we introduce an
      algorithm to suppress these artifacts without distorting the slow wave
      morphology. The algorithm generates a cycle averaged ventilation signal by
      shifting the raw signal by its ventilation period. The cycle averaged ventilation
      signal is then subtracted from the slow wave recording. The algorithm was
      validated using signal to noise ratio (SNR) and Pearson correlation coefficient
      (PCC) on synthetic signals and SNR with experimental recordings. With synthetic
      data, SNR and PCC, improved by 7.29+/-1.14 dB and 0.23+/-0.15.With experimental
      data SNR improved by 2.66+/-0.60 dB. This method improves the slow wave signal
      content revealing a more accurate estimate of the slow wave morphology. The
      application of this method will lead to improved analysis of slow wave recordings
      to understand gut function.

PMID- 29060473
TI  - An adaptive prediction method for signal fusion.
AB  - Many biomedical signal processing applications include the significant challenge
      of sensor data fusion. In this work, an adaptive prediction method fuses a
      relatively higher bandwidth, lower absolute accuracy (fast) signal with a
      relatively lower bandwidth, higher absolute accuracy (accurate) signal of the
      same quantity into a combined signal that is both fast and accurate. Iterative
      estimates of model parameters minimize a regularized mean square prediction error
      that arises from using the fast signal to predict the accurate signal. We
      illustrate the method by fusing a lower bandwidth porcine thermal dilution
      cardiac output signal with a relatively higher bandwidth, less accurate
      peripheral arterial pressure pulse contour cardiac output signal. The combined
      cardiac output signal has both thermal dilution accuracy and pulse contour
      bandwidth.

PMID- 29060474
TI  - Establishing and validating a new source analysis method using phase.
AB  - Electroencephalogram (EEG) measures the brain oscillatory activity non
      invasively. The localization of deep brain generators of the electric fields is
      essential for understanding neuronal function in healthy humans and for damasking
      specific regions that cause abnormal activity in patients with neurological
      disorders. The aim of this study was to test whether the phase estimation from
      scalp data can be reliably used to identify the number of dipoles in source
      analyses. The steps performed included: i) modeling different phasic oscillatory
      signals using auto-regressive processes at a particular frequency, ii) simulation
      of two different noises, namely white and colored noise, having different signal
      to-noise ratios, iii) simulation of dipoles at different areas in the brain and
      iv) estimation of the number of dipoles by calculating the phase differences of
      the simulated signals. Moreover we applied this method of source analysis on real
      data from temporal lobe epilepsy (TLE) patients. The analytical framework was
      successful in identifying the sources and their orientations in the simulated
      data and identified the epileptogenic area in the studied patients which was
      confirmed by pathological studies after TLE surgery.

PMID- 29060475
TI  - Evaluating the effectiveness of different external cues on non-invasive brain
      computer interfaces.
AB  - Although BCI technology has vastly improved in the last few years, very little
      research has been done into how different types of cues may affect the resulting
      signal. We have conducted preliminary work to examine the effects of using
      auditory versus visual cues on MRCP signal detection. While our sample size was
      small (n=5), the data for auditory and visual cues were not statistically
      different for young, healthy participants, suggesting that they are comparable
      for the parameters analyzed. Our results indicated that audio and visual cues
      likely produce similar MRCP signals, which is useful information for designing
      non-invasive BCIs. Future work includes expanding the sample size and conducting
      work with special needs populations, such as children with Autism Spectrum
      Disorder (ASD), who are known to have strong preferences for different
      interfaces.

PMID- 29060476
TI  - Cortico-muscular coherence enhancement via coherent Wavelet enhanced Independent
      Component Analysis.
AB  - Functional coupling between the motor cortex and muscle activity is usually
      detected and characterized using the spectral method of cortico-muscular
      coherence (CMC) between surface electromyogram (sEMG) and electroencephalogram
      (EEG) recorded synchronously under motor control task. However, CMC is often weak
      and not easily detectable in all individuals. One of the reasons for the low
      levels of CMC is the presence of noise and components unrelated to the considered
      tasks in recorded sEMG and EEG signals. In this paper we propose a method for
      enhancing relative levels of sEMG components coherent with synchronous EEG
      signals via a variant of Wavelet Independent Component Analysis combined with a
      novel component selection algorithm. The effectiveness of the proposed algorithm
      is demonstrated using data collected in neurophysiologcal experiments.

PMID- 29060477
TI  - Reliable gradient search directions for kurtosis-based deflationary ICA:
      Application to physiological signal processing.
AB  - Efficient gradient search directions for the optimisation of the kurtosis-based
      deflationary RobustICA algorithm in the case of real-valued data are proposed in
      this paper. The proposed scheme employs, in the gradient-like algorithm typically
      used to optimise the considered kurtosis-based objective function, search
      directions computed from a more reliable approximation of the negentropy than the
      kurtosis. The proposed scheme inherits the exact line search of the conventional
      RobustICA for which a good convergence property through a given direction is
      guaranteed. The efficiency of the proposed scheme is evaluated in terms of
      estimation quality, the execution time and the iterations count as a function of
      the number of used sensors and for different signal to noise ratios in the
      contexts of non-invasive epileptic ElectroEncephaloGraphic (EEG) and Magnetic
      Resonance Spectroscopic (MRS) analysis. The obtained results show that the
      proposed approach offer the best estimation performance/iterations count and
      execution time trade-off, especially in the case of high number of sensors.

PMID- 29060478
TI  - Real-time fetal ECG extraction from multichannel abdominal ECG using compressive
      sensing and ICA.
AB  - An improved method for separation of fetal electrocardiogram (fECG) from
      abdominal electrocardiogram (abdECG) is proposed in this paper. Proposed method
      combines two widely used techniques i.e. compressive sensing (CS) and independent
      component analysis (ICA). Separation of fECG is carried out by applying ICA
      directly on the compressed signal. The efficient improved lp-regularized least
      sqaures (lp-RLS) algorithm is used for signal reconstruction, which provides
      better reconstruction quality and less processing time in comparison with other
      existing methods. The proposed algorithm is evaluated and tested on Physionet
      datasets which contain 75 records in set-A, 100 records in set-B and 6 records in
      Silesia dataset. The obtained outcomes reveal that proposed algorithm shows
      promising results (Sensitivity S=92%, Positive predictivity P+ = 93%, F1 measure
      = 92.5% with average percentage root-mean-square difference PRD =6.89% and
      Execution time= 2.91 sec.). The results also indicate that there is a substantial
      improvement in quality of reconstructed signal which is achieved by maintaining
      lowest PRD.

PMID- 29060479
TI  - A reliable brain-computer interface based on SSVEP using online recursive
      independent component analysis.
AB  - This paper presents a reliable brain-computer interface (BCI) based on a steady
      state visually evoked potential (SSEVP) method using online recursive independent
      component analysis (ORICA) with denoising. The proposed system includes a visual
      stimulator, a front-end data acquisition module, an ORICA module, a power
      spectrum density (PSD)-based noise channel detection module, a denoising module,
      and an EEG reconstruction module, and a detection module using canonical
      correlation analysis (CCA). The system with the proposed PSD-based denoising
      mechanism is simulated using test patterns of 9-Hz and 10-Hz SSEVP-based EEG raw
      data stream with an 8-second sliding window length with a 1-second step size
      under the condition of 128 Hz sampling rate. The accuracy of the detection is
      approximately 88% and 95% hit rate for 9-Hz and 10-Hz test patterns,
      respectively.

PMID- 29060480
TI  - Linear time-varying model characterizes invasive EEG signals generated from
      complex epileptic networks.
AB  - Electrocorticography (ECoG) and stereotactic electroencephalography (SEEG) are
      popular tools for studying neural mechanisms governing behavior and neural
      disorders, such as epilepsy. In particular, clinicians are interested in
      identifying brain regions that start seizures, i.e., the epileptogenic zone (EZ)
      from such invasive recordings. Currently, they visually inspect signals from each
      electrode to locate abnormal activity, and are not informed by predictive models
      that can characterize such recordings and potentially increase accuracy in
      localizing the EZ. In this paper, we test whether a simple linear time varying
      (LTV) model is sufficient to characterize both ECoG and SEEG activity.
      Specifically, we construct linear time invariant models in consecutive time
      windows before, during and after seizure events creating an LTV model from data
      collected in one ECoG and one SEEG patient. We find that these LTV models
      accurately reconstruct both ECoG and SEEG time series measured suggesting that
      these LTV models can be used for EZ localization.

PMID- 29060481
TI  - Functional Clustering approach for the analysis of Stereo-EEG activity patterns
      in correspondence of epileptic seizures.
AB  - In this study, a functional clustering approach is proposed and tested for the
      identification of brain functional networks emerging during sleep-related
      seizures. Stereo-EEG signals recorded in patients with Type II Focal Cortical
      Dysplasia (FCD type II), were analyzed. This novel approach is able to identify
      the network configuration changes in pre-ictal and early ictal periods, by
      grouping Stereo-EEG signals on the basis of the Cluster Index, after wavelet
      multiscale decomposition. Results showed that the proposed method is able to
      detect clusters of interacting leads, mainly overlapped on the Epileptogenic Zone
      (EZ) identified by a clinical expert, with distinctive configurations related to
      analyzed frequency ranges. This suggested the presence of coupling activities
      between the elements of the epileptic system at different frequency scales.

PMID- 29060482
TI  - Improved neonatal seizure detection using adaptive learning.
AB  - In neonatal intensive care units performing continuous EEG monitoring, there is
      an unmet need for around-the-clock interpretation of EEG, especially for
      recognizing seizures. In recent years, a few automated seizure detection
      algorithms have been proposed. However, these are suboptimal in detecting brief
      duration seizures (<; 30s), which frequently occur in neonates with severe
      neurological problems. Recently, a multi-stage neonatal seizure detector,
      composed of a heuristic and a data-driven classifier was proposed by our group
      and showed improved detection of brief seizures. In the present work, we propose
      to add a third stage to the detector in order to use feedback of the Clinical
      Neurophysiologist and adaptively retune a threshold of the second stage to
      improve the performance of detection of brief seizures. As a result, the false
      alarm rate (FAR) of the brief seizure detections decreased by 50% and the
      positive predictive value (PPV) increased by 18%. At the same time, for all
      detections, the FAR decreased by 35% and PPV increased by 5% while the good
      detection rate remained unchanged.

PMID- 29060483
TI  - Epileptic seizure detection based on expected activity measurement and Neural
      Network classification.
AB  - Epilepsy is known as the second reason to visit a neurophysiologist after
      migraine. In this paper, we propose a new approach to automatically detect crises
      of epilepsy in an Electroencephalogram (EEG). Our algorithm is based on image
      transformation, Wavelet Decomposition (DWT) and taking advantage of the
      correlation between wavelet coefficients in each sub-band. Therefore, an Expected
      Activity Measurement (EAM) is calculated for each coefficient as a feature
      extraction method. These features are fed into back propagation Neural Network
      (ANN) and the periods with epileptic seizures and non-seizures are classified.
      Our approach is validated using a public dataset and the results are very
      promising, reaching accuracy up to 99.44% for detection epileptic seizures.

PMID- 29060484
TI  - Respiration estimation and apnea detection using fuzzy logic.
AB  - This paper presents a fuzzy logic-based respiration monitoring algorithm that is
      capable of providing accurate respiration rate and detecting apnea episodes. The
      proposed algorithm employs several signal processing techniques to extract useful
      features that signify different respiratory behaviors. We implement a fuzzy logic
      based system that examines the extracted respiratory signal features and
      categorizes the respiratory signals into respiration, body motion, and apnea. The
      performance of the underlying algorithm is validated using both the MIT
      physiology database and in-house respiration measurements.

PMID- 29060485
TI  - Automatic picking of snore events from overnight breath sound recordings.
AB  - Snoring is one of the earliest symptoms of Obstructive Sleep Apnea (OSA).
      However, the unavailability of an objective snore definition is a major obstacle
      in developing automated snore analysis system for OSA screening. The objectives
      of this paper is to develop a method to identify and extract snore sounds from a
      continuous sound recording following an objective definition of snore that is
      independent of snore loudness. Nocturnal sounds from 34 subjects were recorded
      using a non-contact microphone and computerized data-acquisition system. Sound
      data were divided into non-overlapping training (n = 21) and testing (n = 13)
      datasets. Using training dataset an Artificial Neural Network (ANN) classifier
      were trained for snore and non-snore classification. Snore sounds were defined
      based on the key observation that sounds perceived as 'snores' by human are
      characterized by repetitive packets of energy that are responsible for creating
      the vibratory sound peculiar to snorers. On the testing dataset, the accuracy of
      ANN classifier ranged between 86 - 89%. Our results indicate that it is possible
      to define snoring using loudness independent, objective criteria, and develop
      automated snore identification and extraction algorithms.

PMID- 29060486
TI  - Characterizing the NREM/REM sleep specific obstructive sleep apnea severity using
      snore sounds.
AB  - Obstructive Sleep Apnea (OSA) patients have frequent breathing obstructions and
      upper airway (UA) collapse during sleep. It is clinically important to estimate
      OSA severity separately for Rapid Eye Movement (REM) and non-REM (NREM) sleep
      states, but the task requires Polysomnography (PSG) which uses about 15-20 body
      contact sensors and subjective assessment. Almost all OSA patients snore.
      Vibration in narrowed UA muscles cause snoring in OSA. Moreover, as sleep states
      are associated with distinct breathing patterns and UA muscle tone, REM/NREM
      specific information must be available via snore/breathing sounds. Our previous
      works have shown that snoring carries significant information related to REM/NREM
      sleep states and OSA. We hypothesized that such information from snoring sound
      could be used to characterize OSA specific to REM/NREM sleep states independent
      of PSG. We acquired overnight audio recording from 91 patients (56 males and 35
      females) undergoing PSG and labeled snore sounds as belonging to REM/NREM stages
      based on PSG. We then developed features to capture REM/NREM specific information
      and trained logistic regression (LR) classifier models to map snore features to
      OSA severity bands. Considering separate LR models for males and females, we
      achieved 94-100% sensitivity (84-89% specificity) for NREM stages at the OSA
      severity threshold of 30 events/h. Corresponding sensitivity for REM stages were
      92-97% with specificity 83-85%. Results indicate that it is feasible to estimate
      severe/non-severe OSA in REM/NREM sleep based on snore/breathing sounds alone,
      acquired using simple bedside sound acquisition devices such as mobile phones.

PMID- 29060487
TI  - Blood pressure and cardiovascular parameters during sleep arousals.
AB  - Sleep arousal is generally known as a transient episode of wakefulness into the
      sleepiness. Sleep arousals can be classified based on their association and
      accompany with pathological episodes. In this paper, our objective was to find
      out whether various types of sleep arousals influence on blood pressure and Heart
      Rate Variability (HRV). We analysed continuous Diastolic and Systolic Blood
      Pressures (DBP and SBP), Pulse Transit Time (PTT) as well as High and Low
      Frequency components (HF and LF) of HRV in different types of arousals. We
      developed Slope Index (SI) to determine whether a feature was ascending or
      descending before, during and after the occurrence of a sleep arousal. Slope
      Index Positive Percentage (SIPP) was created and computed for all features to
      find out the percentage of arousals with an ascending trend of a cardiovascular
      feature. In pre-arousal epochs, we obtained SIPPDBP= 48.9%, SIPPSBP = 48.2% and
      SIPPLF = 41%. Whilst during the arousal episodes, the SIPPDBP, SIPPSBP and SIPPLF
      increased to 57.2%, 57.4% and 78.9%, correspondingly. This means that during
      arousal occurrence these parameters were likelier to rise. Whereas SIPP of PTT
      and HF component of HRV during arousals were less than prearousal. This indicated
      PTT and HF were highly probable to drop during the arousal than to rise. The high
      SIPPDBP and SIPPSBP parameters, approximately 76%, during the arousals indicates
      that sleep arousals may cause a sudden increase in blood pressure.

PMID- 29060488
TI  - Serial fusion of Eulerian and Lagrangian approaches for accurate heart-rate
      estimation using face videos.
AB  - Camera-equipped devices are ubiquitous and proliferating in the day-to-day life.
      Accurate heart rate (HR) estimation from the face videos acquired from the low
      cost cameras in a non-contact manner, can be used in many real-world scenarios
      and hence, require rigorous exploration. This paper has presented an accurate and
      near real-time HR estimation system using these face videos. It is based on the
      phenomenon that the color and motion variations in the face video are closely
      related to the heart beat. The variations also contain the noise due to facial
      expressions, respiration, eye blinking and environmental factors which are
      handled by the proposed system. Neither Eulerian nor Lagrangian temporal signals
      can provide accurate HR in all the cases. The cases where Eulerian temporal
      signals perform spuriously are determined using a novel poorness measure and then
      both the Eulerian and Lagrangian temporal signals are employed for better HR
      estimation. Such a fusion is referred as serial fusion. Experimental results
      reveal that the error introduced in the proposed algorithm is 1.8+/-3.6 which is
      significantly lower than the existing well known systems.

PMID- 29060489
TI  - A simple non-contact vital sensing method using Doppler sensors applicable to
      multiple targets.
AB  - This paper proposed a new very simple method for non-contact vital sensing using
      Doppler sensors. It is emphasized that the proposed method can cope with multiple
      bodies even if they are closely located. The proposed method enables us to
      estimate (1) The number of signal (NOS), (2) the fundamental waveform, (3) the
      period, and (4) Direction of arrival (DOA), for each of the incoming signals. In
      addition, the proposed method is computationally effective so that it is
      advantageous for the hardware implementation. Some numerical examples are
      provided for performance verification.

PMID- 29060490
TI  - Automated analysis of in meal eating behavior using a commercial wristband IMU
      sensor.
AB  - Automatic objective monitoring of eating behavior using inertial sensors is a
      research problem that has received a lot of attention recently, mainly due to the
      mass availability of IMUs and the evidence on the importance of quantifying and
      monitoring eating patterns. In this paper we propose a method for detecting food
      intake cycles during the course of a meal using a commercially available
      wristband. We first model micro-movements that are part of the intake cycle and
      then use HMMs to model the sequences of micro-movements leading to mouthfuls.
      Evaluation is carried out on an annotated dataset of 8 subjects where the
      proposed method achieves 0:78 precision and 0:77 recall. The evaluation dataset
      is publicly available at http://mug.ee.auth.gr/intake-cycle-detection/.

PMID- 29060491
TI  - Non-contact acquisition of respiration and heart rates using Doppler radar with
      time domain peak-detection algorithm.
AB  - The non-contact measurement of the respiration rate (RR) and heart rate (HR)
      using a Doppler radar has attracted more attention in the field of home
      healthcare monitoring, due to the extremely low burden on patients,
      unconsciousness and unconstraint. Most of the previous studies have performed the
      frequency-domain analysis of radar signals to detect the respiration and
      heartbeat frequency. However, these procedures required long period time
      (approximately 30 s) windows to obtain a high-resolution spectrum. In this study,
      we propose a time-domain peak detection algorithm for the fast acquisition of the
      RR and HR within a breathing cycle (approximately 5 s), including inhalation and
      exhalation. Signal pre-processing using an analog band-pass filter (BPF) that
      extracts respiration and heartbeat signals was performed. Thereafter, the HR and
      RR were calculated using a peak position detection method, which was carried out
      via LABVIEW. To evaluate the measurement accuracy, we measured the HR and RR of
      seven subjects in the laboratory. As a reference of HR and RR, the persons wore
      contact sensors i.e., an electrocardiograph (ECG) and a respiration band. The
      time domain peak-detection algorithm, based on the Doppler radar, exhibited a
      significant correlation coefficient of HR of 0.92 and a correlation coefficient
      of RR of 0.99, between the ECG and respiration band, respectively.

PMID- 29060492
TI  - Effect of motion artifact on digital camera based heart rate measurement.
AB  - Remote health monitoring is an emerging field in biomedical technology. Digital
      camera based heart rate measurement method is a recent development which would
      make remote health monitoring reliable and sustainable in future. This paper
      presents an investigation on the effect of motion artifact on digital camera
      based heart rate measurement. The paper will discuss details on the principles
      and effects of motion artifacts on photoplethysmography signals. An experiment is
      conducted using publicly available MAHNOB-HCI database. We have investigated the
      effects of static scenarios, scenarios involving rigid motion and scenarios
      involving non-rigid motion. The experiment was tested on state of the art digital
      camera based heart rate measuring methods. The results showed the effectiveness
      of the methods and provide a direction to overcome/minimize the effect of motion
      artifacts for future research.

PMID- 29060493
TI  - Classifying hard and soft bone tissues using drilling sounds.
AB  - The purpose of this study was to investigate if the sounds generated during bone
      drilling could be used to classify between hard (cortical) and soft (cancellous)
      tissues. Bone drilling is performed in many surgical procedures throughout the
      world. Inadvertent deviation from the correct drill direction may result in
      injuries to sensitive anatomical structures such as nerve and vessels. Therefore,
      to increase the safety of such procedures, it is necessary to identify different
      bone tissues. The cortical and cancellous tissues of six bovine tibia pieces were
      drilled and the generated sounds were recorded. Each record was analyzed in
      different frequency regions based on the spectrograms. From each region, short
      time Fourier transform (STFT) coefficients were computed and averaged accordingly
      to obtain n bins. The total bins of all frequency regions were chosen as the
      features. A support vector machine (SVM) algorithm was selected for
      classification and the performance was evaluated in two training/testing
      scenarios: leave one bone out (LOBO) and bone specific (BSP). The average total
      accuracy on the testing data was 70.9% and 83% for LOBO and BSP respectively. The
      results indicated that the drilling sounds obtained from various bone pieces
      could be used to develop a classification model that had promising performance on
      identifying hard and soft components of a new bone piece.

PMID- 29060494
TI  - Predictive local receptive fields based respiratory motion tracking for motion
      adaptive radiotherapy.
AB  - Extracranial robotic radiotherapy employs external markers and a correlation
      model to trace the tumor motion caused by the respiration. The real-time tracking
      of tumor motion however requires a prediction model to compensate the latencies
      induced by the software (image data acquisition and processing) and hardware
      (mechanical and kinematic) limitations of the treatment system. A new prediction
      algorithm based on local receptive fields extreme learning machines (pLRF-ELM) is
      proposed for respiratory motion prediction. All the existing respiratory motion
      prediction methods model the non-stationary respiratory motion traces directly to
      predict the future values. Unlike these existing methods, the pLRF-ELM performs
      prediction by modeling the higher-level features obtained by mapping the raw
      respiratory motion into the random feature space of ELM instead of directly
      modeling the raw respiratory motion. The developed method is evaluated using the
      dataset acquired from 31 patients for two horizons in-line with the latencies of
      treatment systems like CyberKnife. Results showed that pLRF-ELM is superior to
      that of existing prediction methods. Results further highlight that the
      abstracted higher-level features are suitable to approximate the nonlinear and
      non-stationary characteristics of respiratory motion for accurate prediction.

PMID- 29060495
TI  - Motor imagery EEG classification with optimal subset of wavelet based common
      spatial pattern and kernel extreme learning machine.
AB  - Performance of motor imagery based brain-computer interfaces (MI BCIs) greatly
      depends on how to extract the features. Various versions of filter-bank based
      common spatial pattern have been proposed and used in MI BCIs. Filter-bank based
      common spatial pattern has more number of features compared with original common
      spatial pattern. As the number of features increases, the MI BCIs using filter
      bank based common spatial pattern can face overfitting problems. In this study,
      we used eigenvector centrality feature selection method, wavelet packet
      decomposition common spatial pattern, and kernel extreme learning machine to
      improve the performance of MI BCIs and avoid overfitting problems. Furthermore,
      the computational speed was improved by using kernel extreme learning machine.

PMID- 29060496
TI  - Freezing-of-Gait detection using temporal, spatial, and physiological features
      with a support-vector-machine classifier.
AB  - Freezing-of-Gait (FoG) is a syndrome of Parkinson's disease defined by episodes
      when patients show a complete inability to take a step or continue with their
      locomotion. In order to develop closed-loop therapeutic strategies, including
      deep brain stimulation, a reliable means of detecting freezing episodes is
      required. By using wearable accelerometers, freezing episodes can be detected
      with energy-based algorithms when the ratio of the energy in the freeze band (3
      to 8 Hz) to that of the locomotion band (0.5 to 3 Hz) is above a patient-specific
      threshold. However, due to the great variability in patient activity type,
      walking style, and freezing pattern, this detection method often does not work.
      Here we describe a new FoG-detection method that captures temporal, spatial, and
      physiological features and uses a support-vector-machine to classify freezing
      episodes. Since our method uses more diverse features, it is able to more
      robustly detect FoG events. We have shown that when the energy-based method fails
      (e.g., area under the receiver operator curve is ~0.5), our new method performs
      well (e.g., area under ROC curve is 0.96).

PMID- 29060497
TI  - Recognition physical activities with optimal number of wearable sensors using
      data mining algorithms and deep belief network.
AB  - Daily physical activities monitoring is benefiting the health care field in
      several ways, in particular with the development of the wearable sensors. This
      paper adopts effective ways to calculate the optimal number of the necessary
      sensors and to build a reliable and a high accuracy monitoring system. Three data
      mining algorithms, namely Decision Tree, Random Forest and PART Algorithm, have
      been applied for the sensors selection process. Furthermore, the deep belief
      network (DBN) has been investigated to recognise 33 physical activities
      effectively. The results indicated that the proposed method is reliable with an
      overall accuracy of 96.52% and the number of sensors is minimised from nine to
      six sensors.

PMID- 29060498
TI  - PCA-MLP SVM distinction of salivary Raman spectra of dengue fever infection.
AB  - Dengue fever (DF) is a disease of major concern caused by flavivirus infection.
      Delayed diagnosis leads to severe stages, which could be deadly. Of recent, non
      structural protein (NS1) has been acknowledged as a biomarker, alternative to
      immunoglobulins for early detection of dengue in blood. Further, non-invasive
      detection of NS1 in saliva makes the approach more appealing. However, since its
      concentration in saliva is less than blood, a sensitive and specific technique,
      Surface Enhanced Raman Spectroscopy (SERS), is employed. Our work here intends to
      define an optimal PCA-SVM (Principal Component Analysis-Support Vector Machine)
      with Multilayer Layer Perceptron (MLP) kernel model to distinct between positive
      and negative NS1 infected samples from salivary SERS spectra, which, to the best
      of our knowledge, has never been explored. Salivary samples of DF positive and
      negative subjects were collected, pre-processed and analyzed. PCA and SVM
      classifier were then used to differentiate the SERS analyzed spectra. Since
      performance of the model depends on the PCA criterion and MLP parameters, both
      are examined in tandem. Its performance is also compared to our previous works on
      simulated NS1 salivary samples. It is found that the best PCA-SVM (MLP) model can
      be defined by 95 PCs from CPV criterion with P1 and P2 values of 0.01 and -0.2
      respectively. A classification performance of [76.88%, 85.92%, 67.83%] is
      achieved.

PMID- 29060499
TI  - Classification of familiarity based on cross-correlation features between EEG and
      music.
AB  - An approach to recognize the familiarity of a listener with music using both the
      electroencephalogram (EEG) signals and the music signal is proposed in this
      paper. Eight participants listened to melodies produced by piano sounds as simple
      natural stimuli. We classified the familiarity of each participant using cross
      correlation values between EEG and the envelope of the music signal as features
      of the support vector machine (SVM) or neural network used. Here, we report that
      the maximum classification accuracy was 100% obtained by the SVM. These results
      suggest that the familiarity of music can be classified by cross-correlation
      values. The proposed approach can be used to recognize high-level brain states
      such as familiarity, preference, and emotion.

PMID- 29060500
TI  - Assessment of support vector machines and convolutional neural networks to detect
      snoring using Emfit mattress.
AB  - Snoring (SN) is an essential feature of sleep breathing disorders, such as
      obstructive sleep apnea (OSA). In this study, we evaluate epoch-based snoring
      detection methods using an unobtrusive electromechanical film transducer (Emfit)
      mattress sensor using polysomnography recordings as a reference. Two different
      approaches were investigated: a support vector machine (SVM) classifier fed with
      a subset of spectral features and convolutional neural network (CNN) fed with
      spectrograms. Representative 10-min normal breathing (NB) and SN periods were
      selected for analysis in 30 subjects and divided into thirty-second epochs. In
      the evaluation, average results over 10 fold Monte Carlo cross-validation with
      80% training and 20% test split were reported. Highest performance was achieved
      using CNN, with 92% sensitivity, 96% specificity, 94% accuracy, and 0.983 area
      under the receiver operating characteristics curve (AROC). Results showed a 6%
      average increase of performance of the CNN over SVM and greater robustness, and
      similar performance to ambient microphones.

PMID- 29060501
TI  - Using LSTMs to learn physiological models of blood glucose behavior.
AB  - For people with type 1 diabetes, good blood glucose control is essential to
      keeping serious disease complications at bay. This entails carefully monitoring
      blood glucose levels and taking corrective steps whenever they are too high or
      too low. If blood glucose levels could be accurately predicted, patients could
      take proactive steps to prevent blood glucose excursions from occurring. However,
      accurate predictions require complex physiological models of blood glucose
      behavior. Factors such as insulin boluses, carbohydrate intake, and exercise
      influence blood glucose in ways that are difficult to capture through manually
      engineered equations. In this paper, we describe a recursive neural network (RNN)
      approach that uses long short-term memory (LSTM) units to learn a physiological
      model of blood glucose. When trained on raw data from real patients, the LSTM
      networks (LSTMs) obtain results that are competitive with a previous state-of-the
      art model based on manually engineered physiological equations. The RNN approach
      can incorporate arbitrary physiological parameters without the need for
      sophisticated manual engineering, thus holding the promise of further
      improvements in prediction accuracy.

PMID- 29060502
TI  - Convolutional neural network classifier for distinguishing Barrett's esophagus
      and neoplasia endomicroscopy images.
AB  - Barrett's esophagus is a diseased condition with abnormal changes of the cells in
      the esophagus. Intestinal metaplasia (IM) and gastric metaplasia (GM) are two sub
      classes of Barrett's esophagus. As IM can progress to the esophageal cancer, the
      neoplasia (NPL), developing methods for classifying between IM and GM are
      important issues in clinical practice. We adopted a deep learning (DL) algorithm
      to classify three conditions of IM, GM, and NPL based on endimicroscopy images.
      We constructed a convolutional neural network (CNN) architecture to distinguish
      among three classes. A total of 262 endomicroscopy imaging data of Barrett's
      esophagus were obtained from the international symposium on biomedical imaging
      (ISBI) 2016 challenge. 155 IM, 26 GM and 55 NPL cases were used to train the
      architecture. We implemented image distortion to augment the sample size of the
      training data. We tested our proposed architecture using the 26 test images that
      include 17 IM, 4 GM and 5 NPL cases. The classification accuracy was 80.77%. Our
      results suggest that CNN architecture could be used as a good classifier for
      distinguishing endomicroscopy imaging data of Barrett's esophagus.

PMID- 29060503
TI  - A deep learning approach to adherence detection for type 2 diabetics.
AB  - Diabetes has become one of the biggest health problems in the world. In this
      context, adherence to insulin treatment is essential in order to avoid life
      threatening complications. In this pilot study, a novel adherence detection
      algorithm using Deep Learning (DL) approaches was developed for type 2 diabetes
      (T2D) patients, based on simulated Continuous Glucose Monitoring (CGM) signals. A
      large and diverse amount of CGM signals were simulated for T2D patients using a
      T2D adapted version of the Medtronic Virtual Patient (MVP) model for T1D. By
      using these signals, different classification algorithms were compared using a
      comprehensive grid search. We contrast a standard logistic regression baseline to
      Multi- Layer Perceptrons (MLPs) and Convolutional Neural Networks (CNNs). The
      best classification performance with an average accuracy of 77:5% was achieved
      with CNN. Hence, this indicates the potential of DL, when considering adherence
      detection systems for T2D patients.

PMID- 29060504
TI  - Character recognition from trajectory by recurrent spiking neural networks.
AB  - Spiking neural networks are biologically plausible and power-efficient on
      neuromorphic hardware, while recurrent neural networks have been proven to be
      efficient on time series data. However, how to use the recurrent property to
      improve the performance of spiking neural networks is still a problem. This paper
      proposes a recurrent spiking neural network for character recognition using
      trajectories. In the network, a new encoding method is designed, in which varying
      time ranges of input streams are used in different recurrent layers. This is able
      to improve the generalization ability of our model compared with general encoding
      methods. The experiments are conducted on four groups of the character data set
      from University of Edinburgh. The results show that our method can achieve a
      higher average recognition accuracy than existing methods.

PMID- 29060505
TI  - Three drowsiness categories assessment by electroencephalogram in driving
      simulator environment.
AB  - Traffic accidents remain one of the most critical issues in many countries. One
      of the major causes of traffic accidents is drowsiness while driving. Since
      drowsiness is related to human physiological conditions, drowsiness is hard to
      prevent. Several studies have been conducted in assessing drowsiness, especially
      in a driving environment. One of the common methods used is the
      electroencephalogram (EEG). It is known that drowsiness occurs in the central
      nervous system; thus, estimating drowsiness using EEG is the promising way to
      assess drowsiness accurately. In this study, we tried to estimate drowsiness
      using frequency-domain and time-domain analysis of EEG. To validate the
      physiological conditions of the subjects, the Karolinska sleepiness scale (KSS),
      a subject-based assessment of drowsiness condition; and an examiner-based
      assessment known as facial expression evaluation (FEE) were applied. Three
      categories were considered; alert (KSS <; 6; FEE <; 1), weak drowsiness (KSS 6-7;
      FEE 1-2) and strong drowsiness (KSS > 7; FEE > 2). The six parameters (absolute
      and relative power of alpha, ratio of beta/alpha and (theta+alpha)/beta, and
      Hjorth activity and mobility parameters) had statistically significant
      differences between the three drowsiness conditions (P <; 0.001). By using both
      KSS and FEE, these parameters showed high accuracy in detecting drowsiness (up to
      92.9%). Taken together, we suggest that EEG parameters can be used in detecting
      the three drowsiness conditions in a simulated driving environment.

PMID- 29060506
TI  - Objective assessment of perceived effort in listening by employing EEG feature.
AB  - The adjustment of hearing aid devices can heavily depend on the subjective
      feedback of the patients. Our aim is to investigate measures that can be used
      objectively to state a subject's listening effort. To obtain a comprehensive and
      reliable measure as an indicator for a person's listening effort, we need to have
      a better understanding of electroencephalograpic (EEG) activities. Decoding EEG
      signals specifically by the analysis of the instantaneous phase information has
      been a new trend in the last decades. Throughout many studies conducted in the
      past, it has been shown that the instantaneous phase of oscillatory signals reset
      in relation to various cognitive processes. This is based on a hypothesis
      presented for the generation of event related potentials. In this study, we
      measure the degree of phase re-organization through fitting a von Mises
      distribution to EEG recordings. The concentration parameter of a von Mises
      distribution has been shown as an informative feature for reflecting the level of
      attention. This feature has been used for predicting the listening effort and the
      results are compared among three different hearing aid settings.

PMID- 29060507
TI  - Measurement of human enamel mechanical characteristics with resonant ultrasound
      spectroscopy.
AB  - The measurement of enamel mechanical properties offers great significance for the
      design, development and evaluation of clinical dental restorative materials. In
      this paper, resonant ultrasound spectroscopy (RUS) was proposed to measure the
      full second-order elastic tensor of human enamel specimens, and the mechanical
      parameters of human enamel, including Young's moduli, shear moduli and Poisson's
      ratios, were further calculated, which ranged from 64.50 to 80.46 GPa, 26.63 to
      51.86 GPa and 0.18 to 0.40, separately. This study demonstrates that RUS shows
      feasibility on measuring the mechanical properties of human enamel with
      repeatable and nondestructive advantages.

PMID- 29060508
TI  - Estimation of pulse rate from ambulatory PPG using ensemble empirical mode
      decomposition and adaptive thresholding.
AB  - A new method for deriving pulse rate from PPG obtained from ambulatory patients
      is presented. The method employs Ensemble Empirical Mode Decomposition to
      identify the pulsatile component from noise-corrupted PPG, and then uses a set of
      physiologically-relevant rules followed by adaptive thresholding, in order to
      estimate the pulse rate in the presence of noise. The method was optimized and
      validated using 63 hours of data obtained from ambulatory hospital patients. The
      F1 score obtained with respect to expertly annotated data was 0.857 and the mean
      absolute errors of estimated pulse rates with respect to heart rates obtained
      from ECG collected in parallel were 1.72 bpm for "good" quality PPG and 4.49 bpm
      for "bad" quality PPG. Both errors are within the clinically acceptable margin-of
      error for pulse rate/heart rate measurements, showing the promise of the proposed
      approach for inclusion in next generation wearable sensors.

PMID- 29060509
TI  - Non-invasive diagnosis of non-alcoholic fatty liver disease (NAFLD) using
      ultrasound image echogenicity.
AB  - This paper introduces a non-invasive, quantitative technique to diagnose the
      progression of non-alcoholic fatty liver disease (NAFLD). The method is
      predicated on two fundamental principles: 1) the speed of sound in a fatty liver
      is lower than that in a healthy liver and 2) the quality of an ultrasound image
      is maximized when the beamformer's speed of sound matches the true speed of sound
      in the tissue being examined. The proposed method uses the echogenicity of an
      ultrasound image as a quantitative measure to estimate the true speed of sound
      within the liver parenchyma and capture its correlation with the underlying fat
      content. The proposed technique was evaluated in simulations and then tested ex
      vivo on sheep liver, mice liver (healthy and fatty) and tissue-mimicking
      phantoms. In the case of the phantom and sheep liver, the method was able to
      estimate the true speed of sound with errors of less than 0.5%; in the case of
      the mice livers, the method was able to accurately estimate the speed of sound
      within the livers (less than 1% error) and capture the correlation between fat
      content and speed of sound. Thereby, demonstrating the capability of ultrasound
      technology to non-invasively, quantitatively, and accurately diagnose NAFLD at
      point of care.

PMID- 29060510
TI  - Comparison of electrohysterogram characteristics during uterine contraction and
      non-contraction during labor.
AB  - Uterine contraction is one of the most important indication in the labor
      progression. Electrohysterogram (EHG) is a promising method for monitoring
      uterine contraction and discriminating efficient and inefficient contractions.
      This study aims to analyze the difference of EHG signals between two groups. EHG
      signals are recorded with abdominal electrodes from 20 pregnant women, including
      10 in term labor group and 10 in non-labor group. Typical linear and nonlinear
      characteristics of EHG signals, including root mean square (RMS), peak frequency
      (PF), median frequency (MDF), mean frequency (MNF), parameters from wavelet
      decomposition (W4, W5) and time reversibility (Tr) are extracted. These
      characteristics are compared between contraction and non-contraction in term
      labor group and non-labor group. The result shows that RMS, W4 and W5 of
      contraction are significantly larger than non-contraction both within term labor
      group and between two groups (all p<;0.001). However, MDF and MNF are
      significantly smaller (all p<;0.05). Furthermore, all characteristics of non
      contraction show no significant difference between two groups, except MNF. The
      variability of RMS, W4, W5 and Tr of contraction are significantly larger than
      non-contraction both within term labor group and between two groups (all p<;0.05,
      with p<;0.001 for W5 and Tr). However, the variability of MDF, PF and MNF are
      significantly smaller (all p<;0.05). Moreover, the variability of all
      characteristics of non-contraction shows no significant difference between two
      groups, except MNF. We have shown that characteristics of EHG signals and their
      variability during contraction are quite different from non-contraction.
      Therefore, it is feasible to separate uterine contractions and monitor uterine
      activity with EHG signals.

PMID- 29060511
TI  - Performance comparison of wavelet based denoising methods on discontinuous
      adventitious lung sounds.
AB  - Crackles and their time-domain characteristics provide important clues about
      different lung diseases. In this paper, we aim to de-noise synthetically produced
      crackles under various noise levels while preserving their information bearing
      parts which significantly affect crackle parameters. Classical wavelet based de
      noising algorithms are deteriorated by sharp-sudden noise changes and produce
      Gibbs like fluctuations. On the other hand, total variation based algorithms,
      which are capable of alleviating the drawbacks of the classical wavelet based
      algorithms, are failed when dealing with piecewise-smooth signals like crackles
      and generate unwanted flat regions on the de-noised signals. Proposed wavelet
      total variation based de-noising is succeed in removing undesired artefacts
      originating from both classical wavelet and total variation de-noising. The
      proposed method is compared with classical wavelet based de-noising methods in
      terms of root mean square error under various white Gaussian noise levels (0 - 20
      dB SNR). Moreover, in order to emphasize the de-noising ability of the methods,
      without deforming crackle waveform, time and frequency domain representation of a
      noisy and de-noised crackle is validated visually.

PMID- 29060512
TI  - Analysis of dynamic antral scintigraphy using empirical mode decomposition.
AB  - In this work, we proposed to use the empirical mode decomposition (EMD) to
      analyze signals from dynamic antral scintigraphy (DAS) for antral contraction
      rate estimation. The proposed EMD-Fourier method analyzes a DAS time-activity
      curve (TAC) which is called a DAS signal by estimating the frequency from the
      Fourier transform of each intrinsic mode function (IMF), thus yielding multiple
      frequency values for each TAC as opposed to one frequency value obtained from the
      conventional Fourier method. Twenty-three TACs extracted from DAS data acquired
      on twenty-three healthy volunteers were analyzed using both the EMD-Fourier
      method and the Fourier method. The mean and standard deviation of frequency
      across all volunteers were computed. The result showed that the EMD-Fourier
      method provided a reduction of SD-to-mean ratio from the Fourier method ranging
      from 64.3% to 85.8%. The mean frequencies from the third IMF in the EMD-Fourier
      method and from the Fourier method were 2.76 and 3.44 cycles per minute were
      close to a widely-used normal antral contraction rate (3.0 cycles per minute),
      while the EMD-Fourier method yielded significant SD reduction (from 4.77 to 0.57:
      p <; 0.0001). Moreover, it was found that the first IMF yielded a frequency
      estimate of 11.26 +/- 2.2 cycles per minute, while the second IMF yielded a
      frequency estimate of 4.3 +/- 1.3 cycles per minute, which are similar to the
      contraction rates of the duodenum and the large intestine, respectively.

PMID- 29060513
TI  - Feature reconstruction of LFP signals based on PLSR in the neural information
      decoding study.
AB  - To solve the problems of Signal-to-Noise Ratio (SNR) and multicollinearity when
      the Local Field Potential (LFP) signals is used for the decoding of animal motion
      intention, a feature reconstruction of LFP signals based on partial least squares
      regression (PLSR) in the neural information decoding study is proposed in this
      paper. Firstly, the feature information of LFP coding band is extracted based on
      wavelet transform. Then the PLSR model is constructed by the extracted LFP coding
      features. According to the multicollinearity characteristics among the coding
      features, several latent variables which contribute greatly to the steering
      behavior are obtained, and the new LFP coding features are reconstructed.
      Finally, the K-Nearest Neighbor (KNN) method is used to classify the
      reconstructed coding features to verify the decoding performance. The results
      show that the proposed method can achieve the highest accuracy compared to the
      other three methods and the decoding effect of the proposed method is robust.

PMID- 29060514
TI  - Gender differences in dynamic functional connectivity based on resting-state
      fMRI.
AB  - Many neuroscience studies have found brain differences lead to the gender
      differences in behavior and cognitive ability. Functional connectivity is a
      common and effective measure to characterize brain. Most current studies based on
      fMRI functional connectivity basically assumed temporal stationarity across the
      duration of scanning, and thought that brain functional connectivity was constant
      in a certain period of time. However, some studies revealed that the functional
      connectivity was dynamic and fluctuant over time. Dynamic functional connectivity
      could more accurately describe changes in neural activity. A high value of
      flexibility indicates frequent interactions between regions. In this article,
      gender differences in global brain flexibility were further investigated, and
      twelve brain regions with significantly flexibility differences were found. The
      female's flexibility is lower than male's in the amygdala, hippocampus, and
      parahippocampal gyrus. And in the temporal lobe, precuneus, middle cingulate
      gyrus, superior occipital gyrus, and inferior occipital gyrus the flexibility of
      male group is lower than female group. The findings may improve the understanding
      and provide new insights into gender differences on behaviors and cognition from
      the perspective of resting-state brain function.

PMID- 29060515
TI  - Physical activity classification using time-frequency signatures of motion
      artifacts in multi-channel electrical impedance plethysmographs.
AB  - Physical activities are known to introduce motion artifacts in electrical
      impedance plethysmographic (EIP) sensors. Existing literature considers motion
      artifacts as a nuisance and generally discards the artifact containing portion of
      the sensor output. This paper examines the notion of exploiting motion artifacts
      for detecting the underlying physical activities which give rise to the artifacts
      in question. In particular, we investigate whether the artifact pattern
      associated with a physical activity is unique; and does it vary from one human
      subject to another? Data was recorded from 19 adult human-subjects while
      conducting 5 distinct, artifact inducing, activities. A set of novel features
      based on the time-frequency signatures of the sensor outputs are then
      constructed. Our analysis demonstrates that these features enable high accuracy
      detection of the underlying physical activity. Using an SVM classifier we are
      able to differentiate between 5 distinct physical activities (coughing, reaching,
      walking, eating and rolling-on-bed) with an average accuracy of 85.46%.
      Classification is performed solely using features designed specifically to
      capture the time-frequency signatures of different physical activities. This
      enables us to measure both respiratory and motion information using only one type
      of sensor. This is in contrast to conventional approaches to physical activity
      monitoring; which rely on additional hardware such as accelerometers to capture
      activity information.

PMID- 29060516
TI  - Variation-based sparse source imaging in localizing uterine activity.
AB  - Electrohysterogram source imaging, i.e., moving from the electrode/sensor space
      to the source space using EHG signals, provide an estimate of spatial
      distributions of uterine activity at millisecond scale. This paper aims to study
      the ability of different distributed source localization methods to recover
      uterine electrical activity sources. Performance was quantified using a detection
      accuracy index. Our result suggests that the variation based method is able to
      reconstruct extended uterus sources with the overall high accuracy, where the
      increasing of the electrodes numbers and the decreasing of the fat thickness
      induce a better accuracy in localization.

PMID- 29060517
TI  - Respiratory sounds classification using statistical biomarker.
AB  - In this paper, we have proposed a new feature extraction technique based on
      statistical morphology of lung sound signal (LS). This work attempts to (i)
      generate certain intrinsic mode functions (IMFs), (ii) select a set of
      informative IMFs and (iii) extract relevant features from the selected IMFs and
      residue. Feature vector is formed by using the higher order moments: mean,
      standard deviation, skewness and kurtosis and employed as input to the classifier
      models for classification of three types of LS signals: crackle, wheeze and
      normal. The efficiency of these features is examined with an artificial neural
      network (ANN) classifier and compared the results with three baseline methods.
      The proposed method gives a superior performance in term of classification
      accuracy, sensitivity and specificity.

PMID- 29060518
TI  - Significance of modified empirical mode decomposition for ECG denoising.
AB  - The primary objective of the presented work is to exploit the power of modified
      empirical mode decomposition (M-EMD) for the denoising of ECG signals. It is well
      known that the ECG signals get corrupted by a number of noises during the
      recording process. Especially, during wireless ECG recording and ambulatory
      patient monitoring, the signal gets corrupted by additive white Gaussian noise
      (AWGN). Over the years, several techniques have been proposed for ECG denoising.
      Among those, empirical mode decomposition (EMD) and nonlocal means (NLM)
      algorithm are noted to be quite effective. Further, the NLM-based approach is
      better in retaining the morphological characteristics in comparison to the EMD.
      Consequently, the two approaches are effectively combined in this paper so that
      each one complements the other. In the proposed approach, the noisy ECG signal is
      first preprocessed using the NLM algorithm. This is followed by decomposition of
      the partially denoised output through M-EMD. The decomposed components are
      suitably thresholded and then reconstructed to obtain the final denoised signal.
      This largely addresses the issue of under-averaged regions noted in the case of
      NLM-based denoising. Furthermore, the proposed approach is noted to be superior
      to the other existing techniques.

PMID- 29060519
TI  - Evaluation of filtering techniques to extract movement intention information from
      low-frequency EEG activity.
AB  - Low-frequency electroencephalographic (EEG) activity provides relevant
      information for decoding movement commands in healthy subjects and paralyzed
      patients. Brainmachine interfaces (BMI) exploiting these signals have been
      developed to provide closed-loop feedback and induce neuroplasticity. Several
      offline and online studies have already demonstrated that discriminable
      information related to movement can be decoded from low-frequency EEG activity.
      However, there is still not a well-established procedure to guarantee that this
      activity is optimally filtered from the background noise. This work compares
      different configurations of non-causal (i.e., offline) and causal (i.e., online)
      filters to classify movement-related cortical potentials (MRCP) with six healthy
      subjects during reaching movements. Our results reveal important differences in
      MRCP decoding accuracy dependent on the selected frequency band for both offline
      and online approaches. In summary, this paper underlines the importance of
      optimally choosing filter parameters, since their variable response has an impact
      on the classification of low EEG frequencies for BMI.

PMID- 29060520
TI  - Reject option to reduce false prediction rates for EEG-motor imagery based BCI.
AB  - The Filter Bank Common Spatial Pattern (FBCSP) algorithm had been shown to be
      effective in performing multi-class Electroencephalogram (EEG) decoding of motor
      imagery using the one-versus-the-rest approach on the BCI Competition IV Dataset
      IIa. In this paper, we propose a method to reduce false detection rates of
      decoding through a rejection option based on the difference in the posterior
      probability computed by the Naive Bayesian classifier. We applied the proposed
      approach on the BCI Competition IV Dataset IIa, and the results showed a decrease
      in the false detection rates from 34.6 % to 6.9%, while average decoded trials
      decreased from 93.2% to 34.2% using a rejection threshold between 0.1 and 0.9. We
      subsequently formulated a method to optimize the rejection threshold based on the
      maximum F0.5 score. The optimal rejection threshold yielded an average decrease
      in false detection rate to 19.1% with an average of 67.5% of trials decoded. The
      results showed the feasibility of decreasing false detection rates at a cost of
      rejection. Nevertheless, the results suggest that the use of reject option (RO)
      may be used as a training feedback system to train subjects' overt and covert EEG
      control strategies for better (dexterity and safety) continuous control of
      external device.

PMID- 29060521
TI  - Decoding complex imagery hand gestures.
AB  - Brain computer interfaces (BCIs) offer individuals suffering from major
      disabilities an alternative method to interact with their environment.
      Sensorimotor rhythm (SMRs) based BCIs can successfully perform control tasks;
      however, the traditional SMR paradigms intuitively disconnect the control and
      real task, making them non-ideal for complex control scenarios. In this study we
      design a new, intuitively connected motor imagery (MI) paradigm using
      hierarchical common spatial patterns (HCSP) and context information to
      effectively predict intended hand grasps from electroencephalogram (EEG) data.
      Experiments with 5 participants yielded an aggregate classification accuracy
      intended grasp prediction probability-of 64.5% for 8 different hand gestures,
      more than 5 times the chance level.

PMID- 29060522
TI  - Context-aware recursive bayesian graph traversal in BCIs.
AB  - Noninvasive brain computer interfaces (BCI), and more specifically
      Electroencephalography (EEG) based systems for intent detection need to
      compensate for the low signal to noise ratio of EEG signals. In many
      applications, the temporal dependency information from consecutive decisions and
      contextual data can be used to provide a prior probability for the upcoming
      decision. In this study we proposed two probabilistic graphical models (PGMs),
      using context information and previously observed EEG evidences to estimate a
      probability distribution over the decision space in graph based decision-making
      mechanism. In this approach, user moves a pointer to the desired vertex in the
      graph in which each vertex represents an action. To select a vertex, a "Select"
      command, or a proposed probabilistic Selection criterion (PSC) can be used to
      automatically detect the user intended vertex. Performance of different PGMs and
      Selection criteria combinations are compared over a keyboard based on a graph
      layout. Based on the simulation results, probabilistic Selection criterion along
      with the probabilistic graphical model provides the highest performance boost for
      individuals with pour calibration performance and achieving the same performance
      for individuals with high calibration performance.

PMID- 29060523
TI  - Motor imagery classification of upper limb movements based on spectral domain
      features of EEG patterns.
AB  - Surface electromyography pattern recognition methods have been widely applied to
      decode limb movement intentions for prosthesis control. These methods generally
      require amputees to provide sufficient myoelectric signals from their residual
      limb muscles. Previous studies have shown that amputees with high level
      amputation or neuromuscular disorder usually do not have sufficient residual limb
      muscles to provide enough myoelectric signals for accurate identification of limb
      movements. Electroencephalography (EEG), another bioelectric signal associated
      with limb movements has also been proposed and used for decoding the limb motion
      intents of humans. With an attempt to improve the performance of EEG-based method
      in identifying multiple classes of upper limb movement intents, four spectral
      domain features of EEG were proposed in this study. Motor imagery patterns
      associated with five different classes of imagined upper limb movements were
      distinctively decoded based on the four features extracted from 64-channel EEG
      recordings in four transhumeral amputees. Experimental results show that an
      average accuracy of 97.81% was achieved across all the subjects and limb movement
      classes. By applying a sequential channel selection method, an accuracy of around
      95.00% was realized with about 20-channels of EEG. Thus, the proposed method
      might be potential for providing accurate control input for neuroprosthesis.

PMID- 29060524
TI  - A robust beamforming approach for early detection of readiness potential with
      application to brain-computer interface systems.
AB  - Early detection of intention to move, at self-paced voluntary movements from the
      activities of neural current sources on the motor cortex, can be an effective
      approach to brain-computer interface (BCI) systems. Achieving high sensitivity
      and pre-movement negative latency are important issues for increasing the speed
      of BCI and other rehabilitation and neurofeedback systems used by disabled and
      stroke patients and helps enhance their movement abilities. Therefore, developing
      high-performance extractors or beamformers is a necessary task in this regard. In
      this paper, for the sake of improving the beamforming performance in well
      reconstruction of sources of readiness potential, related to hand movement, one
      kind of surface spatial filter (spherical spline derivative on electrode space)
      and the linearly constrained minimum variance (LCMV) beamformer are utilized
      jointly. Moreover, in order to achieve better results, the real head model of
      each subject was created, using individual head MRI, and was used in beamformer
      algorithm. Also, few optimizations were done on reconstructed source signal
      powers to help our template matching classifier with detection of movement onset
      for five healthy subjects. Our classification results show an average true
      positive rate (TPR) of 77.1% and 73.1%, false positive rate (FPR) of 28.96% and
      28.74% and latency of -512.426 +/-396. 7ms and - 360.29 +/-252. 16 ms from
      signals of current sources of motor cortex and sensor space respectively. It can
      be seen that the proposed method has reliable sensitivity and is faster in
      prediction of movement onset and more reliable to be used for online BCI in
      future.

PMID- 29060525
TI  - ARFI variance of acceleration (VoA) for noninvasive characterization of human
      carotid plaques in vivo.
AB  - Rather than degree of stenosis, assessing plaque structure and composition is
      relevant to discerning risk for plaque rupture with downstream ischemic event.
      The structure and composition of carotid plaque has been assessed noninvasively
      using Acoustic Radiation Force Impulse (ARFI) ultrasound imaging. In particular,
      ARFI-derived peak displacement (PD) estimations have been demonstrated for
      discriminating soft (lipid rich necrotic core (LRNC) or intraplaque hemorrhage
      (IPH)) from stiff (collagen (COL) or calcium (CAL)) plaque features; however, PD
      did not differentiate LRNC from IPH or COL from CAL. The purpose of this study is
      to evaluate a new ARFI-based measurement, the variance of acceleration (VoA), for
      differentiating among soft and stiff plaque components. Both PD and VoA results
      were obtained in vivo for a human carotid plaque acquired in a previous study and
      matched to a histological standard analyzed by a pathologist. With VoA, plaque
      feature contrast was increased by an average of 60% in comparison to PD.

PMID- 29060526
TI  - The influence of hepatic steatosis on the evaluation of fibrosis with non
      alcoholic fatty liver disease by acoustic radiation force impulse.
AB  - Acoustic radiation force impulse (ARFI) elastography is a non-invasive method for
      the assessment of liver by measuring liver stiffness. The aim of this study is to
      evaluate the accuracy of ARFI for the diagnosis of liver fibrosis and to assess
      impact of steatosis on liver fibrosis stiffness measurement, in rats model of non
      alcoholic fatty liver disease (NAFLD). The rat models were conducted in 59 rats.
      The right liver lobe was processed and embedded in a fabricated gelatin solution.
      Liver mechanics were measured using shear wave velocity (SWV) induced by acoustic
      radiation force. In rats with NAFLD, the diagnostic performance of ARFI
      elastography in predicting severe fibrosis (F >= 3) and cirrhosis (F >= 4) had
      the areas under the receiver operating characteristic curves (AUROC) of 0.993 and
      0.985. Among rats mean SWV values were significantly higher in rats with severe
      steatosis by histology compared to those mild or without steatosis for F0-F2
      fibrosis stages (3.07 versus 2.51 m/s, P = 0.01). ARFI elastography is a
      promising method for staging hepatic fibrosis with NAFLD in rat models. The
      presence of severe steatosis is a significant factor for assessing the lower
      stage of fibrosis.

PMID- 29060527
TI  - Application of compressive sensing to portable ultrasound elastography.
AB  - Feasibility of applying compressive sensing (CS) to ultrasound radio-frequency
      (RF) data to produce elastography is investigated. The research also compares the
      performance of various CS frameworks associated with three common model bases
      (Fourier transform, discrete cosine transform (DCT), and wave atom (WA)) and two
      reconstruction algorithms (l1 minimization and block sparse Bayesian learning
      (BSBL)) using the quality of B-mode images and elastograms from the RF data
      subsampled and reconstructed by each framework. Results suggest that CS
      reconstruction adopting BSBL algorithm with DCT model basis can yield the best
      results for all the measures tested, and the maximum data reduction rate for
      producing readily discernable elastograms is around 60%.

PMID- 29060528
TI  - Radiofrequency ultrasound data acquisition with a 640-element array transducer
      for strain imaging: Experimental results with phantoms and biological tissue
      samples.
AB  - This paper presents ultrasound elastography results obtained with a 640-element
      array transducer we have recently developed. This probe allows the acquisition of
      series of three adjacent imaging planes over time and therefore makes possible
      the computation of 2-D elastograms, with consideration of out-of-plane motion. In
      this study, elastography experiments were conducted on phantoms and bovine tissue
      samples, and compression was manually applied to the media via the hand-held
      ultrasound transducer. The results obtained with the proposed data acquisition
      and 3-D processing are presented and compared to those from a classical 2-D
      approach.

PMID- 29060529
TI  - Measurement of surface acoustic waves in high-frequency ultrasound: Preliminary
      results.
AB  - Skin lesions change elastic properties near the surface. In the last decades,
      several non-invasive elastography techniques have been developed for detecting
      the mechanical properties of tissue. In particular, harmonic elastography is
      characterized for inducing shear wave propagation by an external vibrator in
      order to estimate shear modulus. However, near the boundary region, propagation
      is governed by surface acoustic waves (SAW). This paper combines crawling waves
      elastography with a high-frequency ultrasound (HFUS) system for the estimation of
      the SAW-to-shear compensation factor when ultrasound (US) gel is used as coupling
      interface. Experiments explore the SAWspeed in a homogeneous phantom with a solid
      water interface in order to corroborate theoretical findings. Subsequently,
      experiments in a solid-US gel interface are conducted in order to find the
      correct compensation factor. Preliminary results suggest that SAW propagation can
      be detected using HFUS, and shear velocity maps can be generated by applying the
      estimated empirical correction factor. This study will potentially avoid the
      underestimation of shear modulus when using SAW-based HFUS elastography which is
      promising for the better diagnosis of skin diseases.

PMID- 29060530
TI  - Shear wave estimation by using Shear Wave Holography with normal vibration:
      Preliminary results.
AB  - Mechanical properties of soft human tissue are linked to their pathological
      state. One way to assess these properties is through the Young modulus
      measurement, which is related to the shear wave speed in the medium when
      considering tissues as nearly incompressible. In order to characterize its
      elastic properties using sonoelastography, we introduce a new technique for shear
      wave estimation from a static interference pattern based on Shear Wave
      Holography. A relation between the mathematical representation of the
      interference pattern and the local shear speed is derived using the Phase
      Derivative approach. The experimental scheme is presented, detailing the
      advantages of the new configuration. Homogeneous and heterogeneous elastic media
      were simulated, generating an interference pattern on them. The shear speed
      estimation algorithm was explained and applied to obtain the speed map,
      calculating the mean value over each medium. The technique was tested on a nearly
      incompressible homogeneous elastic phantom, yielding a maximum and a mean
      estimation error of 6% and 4.6% respectively. Overall, Shear Wave Holography
      using normal vibration is feasible and shows promising results in estimating
      shear wave speed in elastic materials.

PMID- 29060531
TI  - Central sulcus depth and sulcal profile differences between congenitally blind
      and sighted individuals.
AB  - We used BrainVisa software in an exploratory analysis measuring the depth and
      sulcal profile of the central sulci of congenitally blind and sighted
      individuals. We found the greatest differences between the groups at locations on
      the central sulcus corresponding with the pli de passage fronto-parietal moyen
      (PPFM), suggesting a cortical reorganization of the primary sensorimotor area of
      the hand within the central sulcus. This may be in response to the congenitally
      blind individuals' mastery of Braille or general increase of hand use in everyday
      life.

PMID- 29060532
TI  - MRI based objective ischemic core-penumbra quantification in adult clinical
      stroke.
AB  - Objective and non-invasive quantification of ischemic stroke and differentiation
      of salvageable from non-salvageable tissue is critical to treatment planning.
      However current Magnetic Resonance Imaging(MRI) techniques are time consuming and
      rely on manual detection methods. Computer aided preliminary screening of the
      injured tissue could assist neuroradiologists in performing more detailed
      analysis of the lesion components. An established Hierarchical Region Splitting
      (HRS) method was extended to segment lesions from adult patients who suffered a
      clinical stroke using diffusion- and perfusion weighted image (DWI-PWI) maps and
      associated computed maps. Apart from lesion quantification PWI-DWI based HRS was
      also able to automatically quantify core (irrecoverable) the penumbra
      (potentially recoverable) which helped to estimate salvageable tissue. The PWI
      DWI/HRS results were validated by comparing with manually demarcated ground truth
      in terms of performance indices like lesion volume (82.1% accuracy), sensitivity
      (78.8%), specificity (99.3%) and similarity (78.54%) for a dataset of 10 acute
      adult stroke patients. Data sets were classified into severe, moderate and mild
      injuries based on total lesion volume. Proposed PWI-DWI/HRS method demonstrated
      accuracy close to manual lesion demarcation with high performance indices for
      core and penumbra in severe and moderate classes.

PMID- 29060533
TI  - Brain functional connectivity alterations in a rat model of excessive alcohol
      drinking: A resting-state network analysis.
AB  - Alcohol use disorders (AUD) are a major public health concern. Understanding the
      brain network alterations is of the utmost importance to diagnose and develop
      treatment strategies. Employing resting-state functional magnetic resonance
      imaging, we have performed a longitudinal study in a rat model of chronic
      excessive alcohol consumption, to identify functional alterations in brain
      networks triggered by alcohol drinking. Two time points were considered: 1)
      before alcohol consumption (control condition) and 2) after 30 days of alcohol
      drinking (alcohol condition). We first identified nine resting-state networks
      with group independent component analysis. Afterwards, dual regression was
      applied to obtain subject-specific time courses and spatial maps. L2-regularized
      partial correlation analysis between pairs of networks showed that functional
      connectivity (FC) between the retrosplenial-visual and striatal networks
      decreases due to alcohol consumption, whereas FC between the prefrontal-cingulate
      and striatal networks increases. Analysis of subject-specific spatial maps
      revealed FC decreases within networks after alcohol drinking, including the
      striatal, motor-parietal, prefrontal-cingulate, retrosplenial-visual and left
      motor-parietal networks. Overall, our results unveil a generalized decrease in
      brain FC induced by alcohol drinking in genetically predisposed animals, even
      after a relatively short period of exposure (1 month). The only exception to this
      hypo-connectivity state is the functional association between the striatal and
      prefrontal-cingulate networks, which increases after drinking, supporting
      evidence in human alcoholics.

PMID- 29060534
TI  - Difference of Alzheimer's disease sub-groups using two features from intensity
      size zone matrix.
AB  - Alzheimer's disease (AD) is known as one of the important diseases with worldwide
      impact. Unfortunately, we have not found the cause and treatment methods for AD.
      Magnetic resonance imaging (MRI) is an important research for AD research. Many
      recent studies focused on finding imaging biomarker associated with AD and mild
      cognitive impairment (MCI). Texture analysis jointly considers gray-level
      intensity and position of the voxels within a given region of interest (ROI). It
      can lead to better characterization of ROI than conventional approaches. We
      adopted one of the texture analysis methods called intensity size zone matrix
      (ISZM) to compare AD, late MCI (LMCI), early MCI (EMCI) and normal control (NC)
      subjects in both hemispheres of the hippocampus. As a result, we were able to
      distinguish among the sub-groups using the intensity variability feature and size
      zone variability feature computed from ISZM.

PMID- 29060535
TI  - Early axonal damage in normal appearing white matter in multiple sclerosis: Novel
      insights from multi-shell diffusion MRI.
AB  - Conventional diffusion-weighted MR imaging techniques provide limited specificity
      in disentangling disease-related microstructural alterations involving changes in
      both axonal density and myelination. By simultaneously probing multiple diffusion
      regimens, multi-shell diffusion MRI is capable of increasing specificity to
      different tissue sub-compartments and hence separate different contributions to
      changes in diffusion-weighted signal attenuation. Advanced multi-shell diffusion
      models impose significant requirements on the amount of diffusion weighting (i.e.
      gradient coil performance) and angular resolution (i.e. in-scanner subject time),
      which commonly limits their applicability in a clinical setting. In this paper,
      we apply a high-b-value, high angular resolution multi-shell diffusion MRI
      protocol to a population of early multiple sclerosis (MS) patients and healthy
      controls. Through the Composite Hindered and Restricted Model of Diffusion
      (CHARMED) model, we extract indices for axonal density as well as parameters
      sensitive to myelin. We demonstrate increased sensitivity to microstructural
      changes in normal appearing white matter and in lesions in MS as compared to
      traditional models like DTI. These changes appear to be predominantly in axonal
      density, pointing towards the existence of axonal damage mechanisms in early MS.

PMID- 29060536
TI  - Brain age estimation from T1-weighted images using effective local features.
AB  - Statistical analysis using large-scale brain magnetic resonance (MR) image
      databases has examined that brain tissues have age-related morphological changes.
      The age of a subject can be estimated from the brain MR image by evaluating
      morphological changes with healthy aging. This paper proposes an age estimation
      method using local features of T1-weighted MR images. The brain local features
      are defined by volumes of brain tissues parcellated into 1,024 local regions
      defined by the automated anatomical labeling atlas. This paper also proposes the
      effective local feature selection method to improve the accuracy of age
      estimation. We evaluate the accuracy of the proposed method using 1,099 T1
      weighted images from a Japanese MR image database. We also analyze effectiveness
      of each local region for age estimation and discuss its medical implication.

PMID- 29060537
TI  - Wideband phantoms of different body tissues for heterogeneous models in body area
      networks.
AB  - One of the key issues about wireless technologies is their interaction with the
      human body. The so-called internet of things will comprise many devices that will
      transmit either around or through the human body. These devices must be tested
      either in their working medium, when possible, or in the most realistic one. For
      this purpose, tissue-like phantoms are the best alternative to carry out
      realistic analyses of the performance of body area networks. In addition, they
      are the conventional way to certify the compliance of commercial standards by
      these devices. However, the number of phantoms that work in large bandwidths is
      limited in literature. This work aims at presenting chemical solutions that will
      be useful to prepare a variety of wideband tissue phantoms. Besides, the colon
      was mimicked in two ways, the healthy tissue and the malignant one, taking into
      account studies that relate changes on the relative permittivity with cancer.
      They were designed on the basis of acetonitrile in aqueous solutions as described
      in a previous work. Thus, many scenarios could be developed such as multilayers
      which imitate parts of the heterogeneous body.

PMID- 29060538
TI  - A wireless capsule endoscopy steering mechanism using magnetic field platform.
AB  - In this paper, a new steering mechanism for wireless capsule devices is
      presented. The proposed system consists of a platform generating a magnetic field
      to direct and control the motion of a capsule. The platform contains an upper and
      a lower set of electromagnets. A permanent magnet is implanted inside the capsule
      to initiate the movement, which is set by the magnetic field delivered by the
      electromagnets. The total magnetic field at the capsule's location is the sum of
      the contributions of each electromagnet. An experimental setup has been designed
      for testing and comparing between the performance of the capsule mobility in
      practice and simulations.

PMID- 29060539
TI  - A swallowable sensing device platform with wireless power feeding and chemical
      reaction actuator.
AB  - This paper presents a swallowable sensor device that can be ingested orally,
      later passing to the stomach, where the device can indwell for long periods.
      Using wireless communication, it can be egested at any time after it is
      triggered. This device can indwell using a silicone balloon in the
      gastrointestinal tract. A chemical reaction inflates the balloon inside the
      stomach. Then it is deflated to egest the sensor device using an actuator with
      electrolysis of water. Energy for the actuator with electrolysis can be fed
      wirelessly. Near field communication and a flexible antenna are used for power
      feeding and wireless data communication. Because of the flexible balloon and the
      flexible antenna, the device size can be minimized without performance
      degradation.

PMID- 29060540
TI  - Detection of turning freeze in Parkinson's disease based on S-transform
      decomposition of EEG signals.
AB  - Freezing of Gait (FOG) is a highly debilitating and poorly understood symptom of
      Parkinson's disease (PD), causing severe immobility and decreased quality of
      life. Turning Freezing (TF) is known as the most common sub-type of FOG, also
      causing the highest rate of falls in PD patients. During a TF, the feet of PD
      patients appear to become stuck whilst making a turn. This paper presents an
      electroencephalography (EEG) based classification method for detecting turning
      freezing episodes in six PD patients during Timed Up and Go Task experiments.
      Since EEG signals have a time-variant nature, time-frequency Stockwell Transform
      (S-Transform) techniques were used for feature extraction. The EEG sources were
      separated by means of independent component analysis using entropy bound
      minimization (ICA-EBM). The distinctive frequency-based features of selected
      independent components of EEG were extracted and classified using Bayesian Neural
      Networks. The classification demonstrated a high sensitivity of 84.2%, a
      specificity of 88.0% and an accuracy of 86.2% for detecting TF. These promising
      results pave the way for the development of a real-time device for detecting
      different sub-types of FOG during ambulation.

PMID- 29060541
TI  - Detection of gait initiation Failure in Parkinson's disease based on wavelet
      transform and Support Vector Machine.
AB  - Gait initiation Failure (GIF) is the situation in which patients with Parkinson's
      disease (PD) feel as if their feet get "stuck" to the floor when initiating their
      first steps. GIF is a subtype of Freezing of Gait (FOG) and often leads to falls
      and related injuries. Understanding of neurobiological mechanisms underlying GIF
      has been limited by difficulties in eliciting and objectively characterizing such
      gait phenomena in the clinical setting. Studies investigating the effects of GIF
      on brain activity using EEG offer the potential to study such behavior. In this
      preliminary study, we present a novel methodology where wavelet transform was
      used for feature extraction and Support Vector Machine for classifying GIF events
      in five patients with PD and FOG. To deal with the large amount of EEG data, a
      Principal Component Analysis (PCA) was applied to reduce the data dimension from
      15 EEG channels into 6 principal components (PCs), retaining 93% of the
      information. Independent Component Analysis using Entropy Bound Minimization (ICA
      EBM) was applied to 6 PCs for source separation with the aim of improving
      detection ability of GIF events as compared to the normal initiation of gait
      (Good Starts). The results of this analysis demonstrated the correct
      identification of GIF episodes with an 83.1% sensitivity, 89.5% specificity and
      86.3% accuracy. These results suggest that our proposed methodology is a
      promising non-invasive approach to improve GIF detection in PD and FOG.

PMID- 29060542
TI  - Posturography stability score generation for stroke patient using Kinect: Fuzzy
      based approach.
AB  - Aim of this paper is to formulate a posturography stability score for stroke
      patients using fuzzy logic. Postural instability is one of the prominent symptoms
      of stroke, dementia, parkinsons disease, myopathy, etc. and is the major
      precursor of fall. Conventional scoring techniques used to assess postural
      stability require manual intervention and are dependent on live interaction with
      physiotherapist. We propose a novel scoring technique to calculate static
      stability of a person using posturography features acquired by Kinect sensor,
      which do not require any manual intervention or expert guidance, is cost
      effective and hence are ideal for tele rehabilitation purpose. Stability analysis
      is done during Single Limb Stance (SLS) exercise. Kinect sensor is used to
      calculate three features, naming SLS duration, vibration index, calculated from
      mean vibration of twenty joints and sway area of Centre of Mass (CoM). Based on
      the variation of these features, a fuzzy rule base is generated which calculates
      a static stability score. One way analysis of variance (Anova) between a group of
      stroke population and healthy individuals under study validates the reliability
      of the proposed scorer. Generated fuzzy score are comparable with standard
      stability scorer like Berg Balance scale and fall risk assessment tool like Johns
      Hopkins scale. Stability score, besides providing an index of overall stability
      can also be used as a fall predictability index.

PMID- 29060543
TI  - Automated epileptiform spike detection via affinity propagation-based template
      matching.
AB  - Interictal epileptiform spikes are the key diagnostic biomarkers for epilepsy.
      The clinical gold standard of spike detection is visual inspection performed by
      neurologists. This is a tedious, time-consuming, and expert-centered process. The
      development of automated spike detection systems is necessary in order to provide
      a faster and more reliable diagnosis of epilepsy. In this paper, we propose an
      efficient template matching spike detector based on a combination of spike and
      background waveform templates. We generate a template library by clustering a
      collection of spikes and background waveforms extracted from a database of 50
      patients with epilepsy. We benchmark the performance of five clustering
      techniques based on the receiver operating characteristic (ROC) curves. In
      addition, background templates are integrated with existing spike templates to
      improve the overall performance. The affinity propagation-based template matching
      system with a combination of spike and background templates is shown to
      outperform the other four conventional methods with the highest area-under-curve
      (AUC) of 0.953.

PMID- 29060544
TI  - A new infarction detection method based on heart rate variability in rat middle
      cerebral artery occlusion model.
AB  - OBJECTIVE: The present study proposes a cerebral infarction detection algorithm
      based on heart rate variability (HRV). METHODS: It has been reported that
      infarction affects HRV. Therefore, infarction could be detected at an acute stage
      by monitoring HRV. This study uses multivariate statistical process control
      (MSPC), which is a well-known anomaly monitoring method. HRV data shortly after
      infarction onsets are collected by using the middle cerebral artery occlusion
      (MCAO) model in rats. This study prepares 11 MCAO-operated rats and 11 sham
      operated rats. Three sham-operated rats' data are used for model construction of
      MSPC, and the other 19 rats' data are used for its validation. RESULTS: The
      sensitivity and specificity of the proposed algorithm were 82 % and 75 %,
      respectively. CONCLUSION: An infarction onset could be detected at an acute stage
      by monitoring HRV.

PMID- 29060545
TI  - Stroke lesion location influences the decoding of movement intention from EEG.
AB  - Recent studies have demonstrated the efficacy of brain-machine interfaces (BMI)
      for motor rehabilitation after stroke, especially for those patients with severe
      paralysis. However, a cerebro-vascular accident can affect the brain in many
      different manners, and lesions in diverse areas, even from significantly
      different volumes, can lead to similar or equal motor deficits. The location of
      the insult influences the way the brain activates when moving or attempting to
      move a paralyzed limb. Since the essence of a rehabilitative BMI is to precisely
      decode motor commands from the brain, it is crucial to characterize how lesion
      location affects the measured signals and if and how it influences BMI
      performance. This paper compares the performances of an electroencephalography
      (EEG)-based movement intention decoder in two groups of severely paralyzed
      chronic stroke patients: 14 with subcortical lesions and 14 with mixed (i.e.,
      cortical and subcortical) lesions. We show that the lesion location influences
      the performance of the BMI when decoding the movement attempts of the paretic
      arm. The obtained results underline the need for further developments for a
      better individualization of BMI-based rehabilitative therapies for stroke
      patients.

PMID- 29060546
TI  - Automated subdural hematoma segmentation for traumatic brain injured (TBI)
      patients.
AB  - Traumatic brain injury is a serious public health problem in the U.S.
      contributing to a large portion of permanent disability. However, its early
      management and treatment could limit the impact of the injury, save lives and
      reduce the burden of cost for patients as well as healthcare systems. Subdural
      hematoma is one of the most common types of TBI, which its visual detection and
      quantitative evaluation are time consuming and prone to error. In this study, we
      propose a fully auto-mated machine learning based approach for 3D segmentation of
      convexity subdural hematomas. Textural, statistical and geometrical features of
      sample points from intracranial region are extracted based on head Computed
      Tomography (CT) images. Then, a tree bagger classifier is implemented to classify
      each pixel as hematoma or no-hematoma. Our method yields sensitivity, specificity
      and area under the receiver operating curve (AUC) of 85:02%, 73:74% and 0:87
      respectively.

PMID- 29060547
TI  - Compartmental sparse feature selection method for Alzheimer's disease
      identification.
AB  - For high-dimensional magnetic resonance imaging (MRI) data, many feature
      selection methods have been proposed to reduce feature dimension in the study of
      computer-aided Alzheimer's disease (AD) diagnosis. This paper presents a
      compartmental sparse feature selection method used for AD identification. Based
      on the derived atlas-based regions-of-interest (ROIs) of brain, the proposed
      method partitioned the T1-weighted MRI data into several compartments. It
      performs feature selection and classification compartmentally according to the
      local feature dimension estimation and local feature selection using sparse
      principal component analysis (SPCA) method followed with elastic-net logistic
      regression (ENLR) classifier. Experimental results showed that the proposed
      method improves the classification performance for small ROIs with high
      computational efficiency.

PMID- 29060548
TI  - Low grade glioma growth modeling considering chemotherapy and radiotherapy
      effects from magnetic resonance images.
AB  - Studying tumor growth using mathematical models from magnetic resonance (MR)
      images is an important application that is believed to play a major role in
      cancer treatment by predicting tumor evolution, quantifying the response to
      therapy, and treatment planning. Reaction diffusion is the most popular model
      because of its simplicity and consistency with the biological growth process.
      However, most of the current growth models focus on presurgical images and likely
      without treatment. In this paper, we propose a new reaction diffusion model to
      consider the chemotherapy and radiotherapy effects on the tumor growth modelling
      for patients with low grade glioma. The proposed model does not consider the
      tensor information from diffusion tensor imaging. Instead it uses a weighted
      parameter to promote higher diffusivity in white matter. The radiotherapy and
      chemotherapy effects are considered as a loss terms in the proposed model. The
      preliminary results of the proposed model on synthetic and 2 real MR images show
      that, our model can effectively simulate tumor growth with high accuracies when
      treatments are administrated to low grade glioma patients.

PMID- 29060549
TI  - Classification of low-grade and high-grade glioma using multi-modal image
      radiomics features.
AB  - Gliomas are primary brain tumors arising from glial cells. Gliomas can be
      classified into different histopathologic grades according to World Health
      Oraganization (WHO) grading system which represents malignancy. In this paper, we
      present a method to predict the grades of Gliomas using Radiomics imaging
      features. MICCAI Brain Tumor Segmentation Challenge (BRATs 2015) training data,
      its segmentation ground truth and the ground truth labels were used for this
      work. 45 radiomics features based on histogram, shape and gray-level co
      occurrence matrix (GLCM) were extracted from each FLAIR, T1, T1-Contrast, T2
      image to quantify the property of Gliomas. Significant features among 180
      features were selected through L1-norm regularization (LASSO). Based on LASSO
      coefficient and selected feature values, we computed a LASSO score and gliomas
      were classified into low-grade glimoa (LGG) or high-grade glimoa (HGG) through
      logistic regression. Classification result was validated by a 10-fold cross
      validation. Our method achieved accuracy of 0.8981, sensitivity of 0.8889,
      specificity of 0.9074, and area under the curve (AUC) = 0.8870.

PMID- 29060550
TI  - Contribution to speech development of the right anterior putamen revealed with
      multivariate tensor-based morphometry.
AB  - In our previous study1, we suggested that the difference between tensor-based
      metrics in the anterior part of the right putamen between 21 and 18 months age
      groups associated with speech development during this ages. Here we used a
      correlational analysis between verbal scores and determinant of the Jacobian
      matrix to confirm our hypothesis. Significant correlations in anterior part of
      the right putamen between verbal scores and surface metric were revealed in the
      18 and 21 age groups.

PMID- 29060551
TI  - Collision frequency locality-sensitive hashing for prediction of critical events.
AB  - We present a fast, efficient method to predict future critical events for a
      patient. The prediction method is based on retrieving and leveraging similar
      waveform trajectories from a large medical database. Locality-sensitive hashing
      (LSH), our theoretical foundation, is a model-free, sub-linear time, approximate
      search method enabling a fast retrieval of a nearest neighbor set for a given
      query. We propose a new variant of LSH, namely Collision Frequency LSH (CFLSH),
      to further improve the prediction accuracy without sacrificing any speed. The key
      idea is that the more frequently an element and a query collide across multiple
      LSH hash tables, the more similar they are. Unlike the standard LSH which only
      utilizes the linear distance calculation, in CFLSH, the short-listing step from a
      pool of pre-selected candidates filtered by hash functions to the final nearest
      neighbor set relies upon the frequency of collision along with distance
      information. We evaluate CFLSH versus the standard LSH using the L1 and cosine
      distances, for predicting acute hypotensive episodes on arterial blood pressure
      time series data extracted from the MIMIC II database. Our results show that
      CFLSH for the L1 distance has a higher prediction accuracy and further
      accelerates the sub-linear querying time obtained by the standard LSH.

PMID- 29060552
TI  - Optimized automatic sleep stage classification using the normalized mutual
      information feature selection (NMIFS) method.
AB  - Sleep is a very important physiological phenomenon for recovery of physical and
      mental fatigue. Recently, there has been a lot of interest in the quality of
      sleep and the research is actively under way. In particular, it is important to
      have a repetitive and regular sleep cycle for good sleep. However, it takes a lot
      of time to determine sleep stages using physiological signals by experts. In this
      study, we constructed an optimized classifier based on normalized mutual
      information feature selection (NMIFS) and kernel based extreme learning machine
      (K-ELM), and total 4 sleep stages (Awake, weak sleep (stage1+stage2), deep
      sleep(stage3+stage4) and rapid eye movement (REM)) were automatically classified.
      As a results, the average of the accuracy obtained by proposed method (NMIFS+K
      ELM) is 2~3% higher than that of simple method (K-ELM).

PMID- 29060553
TI  - Application of SsVGMM to medical data - classification with novelty detection.
AB  - There is a huge demand to apply classification in medical analysis. A traditional
      classifier requires having training samples from each class. However, in reality,
      it is possible that the testing set may include classes that are not in the
      training set. This inevitably causes an issue: data from a undefined class will
      be assigned to a predefined classes. To tackle this, we propose a semi-supervised
      variational Gaussian mixture model to perform multi-class classification with
      novelty detection. Comparing to some popular novelty detection methods, we
      demonstrate that it gets better performance on a thyroid disease data, by
      generating the distribution of predefined classes and undefined class, without
      explicitly setting a threshold.

PMID- 29060554
TI  - Ensemble transfer learning for Alzheimer's disease diagnosis.
AB  - There is considerable interest in developing inexpensive, nonintrusive diagnostic
      tests for Alzheimer's disease (AD), in the hope these tests will facilitate early
      diagnosis and support design of effective treatments. While tests based on blood
      borne biomarkers such as microRNAs have shown promise, work to date indicates
      these tests often do not generalize well: diagnostic models derived for one
      patient group are not accurate when applied to a new cohort. This paper presents
      a novel ensemble-based transfer learning methodology which induces models that
      provide accurate diagnoses across distinct patient groups without retraining. The
      algorithm combines information from supervised ensemble learning and unsupervised
      ensemble clustering to enable robust transfer learning. The efficacy of the
      approach is illustrated through a case study involving microRNA-based AD
      diagnosis. In this test, we use our algorithm to learn a diagnostic model on data
      from one patient group and then apply the model to a different target group,
      obtaining diagnostic accuracy which actually exceeds that of a state-of-the-art
      model trained directly on the target group.

PMID- 29060555
TI  - Learning about individuals' health from aggregate data.
AB  - There is growing awareness that user-generated social media content contains
      valuable health-related information and is more convenient to collect than
      typical health data. For example, Twitter has been employed to predict aggregate
      level outcomes, such as regional rates of diabetes and child poverty, and to
      identify individual cases of depression and food poisoning. Models which make
      aggregate-level inferences can be induced from aggregate data, and consequently
      are straightforward to build. In contrast, learning models that produce
      individual-level (IL) predictions, which are more informative, usually requires a
      large number of difficult-to-acquire labeled IL examples. This paper presents a
      new machine learning method which achieves the best of both worlds, enabling IL
      models to be learned from aggregate labels. The algorithm makes predictions by
      combining unsupervised feature extraction, aggregate-based modeling, and optimal
      integration of aggregate-level and IL information. Two case studies illustrate
      how to learn health-relevant IL prediction models using only aggregate labels,
      and show that these models perform as well as state-of-the-art models trained on
      hundreds or thousands of labeled individuals.

PMID- 29060556
TI  - Comparing deep neural network and other machine learning algorithms for stroke
      prediction in a large-scale population-based electronic medical claims database.
AB  - Electronic medical claims (EMCs) can be used to accurately predict the occurrence
      of a variety of diseases, which can contribute to precise medical interventions.
      While there is a growing interest in the application of machine learning (ML)
      techniques to address clinical problems, the use of deep-learning in healthcare
      have just gained attention recently. Deep learning, such as deep neural network
      (DNN), has achieved impressive results in the areas of speech recognition,
      computer vision, and natural language processing in recent years. However, deep
      learning is often difficult to comprehend due to the complexities in its
      framework. Furthermore, this method has not yet been demonstrated to achieve a
      better performance comparing to other conventional ML algorithms in disease
      prediction tasks using EMCs. In this study, we utilize a large population-based
      EMC database of around 800,000 patients to compare DNN with three other ML
      approaches for predicting 5-year stroke occurrence. The result shows that DNN and
      gradient boosting decision tree (GBDT) can result in similarly high prediction
      accuracies that are better compared to logistic regression (LR) and support
      vector machine (SVM) approaches. Meanwhile, DNN achieves optimal results by using
      lesser amounts of patient data when comparing to GBDT method.

PMID- 29060557
TI  - Evaluating the association between cardiac and peripheral resistance arms of the
      baroreflex.
AB  - The study proposes an extension of cardiac baroreflex (cBR) sequence analysis,
      traditionally performed over spontaneous fluctuations of heart period and
      systolic arterial pressure, to typify peripheral resistance baroreflex (prBR)
      from spontaneous variations of peripheral resistances and diastolic arterial
      pressure. The prBR baroreflex sensitivity (BRSprBR) and percentage of prBR
      sequences (SEQ%prBR) were computed along with analogous quantities assessed over
      cBR (i.e. BRScBR and SEQ%cBR). The cBR and prBR were typified in healthy subjects
      at rest (REST) and during light bicycle ergometer exercise at 10 percent of the
      maximal effort (EXE). Both cBR and prBR were affected by EXE: indeed, BRScBR and
      SEQ%prBR were significantly reduced. Moreover, while BRScBR and BRSprBR were not
      significantly associated, SEQ%cBR and SEQ%prBR were, and the correlation
      coefficient was positive. This study suggests that prBR can be typified from
      spontaneous variabilities along with the more traditional cBR, thus enlarging the
      possibility of monitoring human cardiovascular control mechanisms.

PMID- 29060558
TI  - Changes in heart rate variability of patients with delirium in intensive care
      unit.
AB  - Delirium is an important syndrome in intensive care unit (ICU) patients, however,
      its characteristics are still unclear. Many evidences showed that this syndrome
      can be related to the autonomic instability. In this study, we aimed to
      investigate the possible alterations of autonomic nervous system (ANS) in
      delirium patients in ICU. Electrocardiography (ECG) of every ICU patient was
      measured during routine daily ICU care, and the data were gathered to evaluate
      the heart rate variability (HRV). HRV of total 60 patients were analyzed in time,
      frequency and non-linear domains. As a result, we found that heart rates of
      delirium patients were more variable and irregular than non-delirium patients.
      These findings may facilitate early detection and prevention of delirium in ICU.

PMID- 29060559
TI  - A stochastic and mathematically integrative model of the control of human heart
      rate.
AB  - The innate variability of the heart rate contains both random and temporally
      scaled components. The objective of this study was to design a stochastic and
      mathematically integrative model (SIM) of the control of human heart rate that
      could replicate the cardiac rhythm during rest and two distinct states of
      exercise. Heartbeat-to-heartbeat interval (RRI) were recorded from 8 healthy
      subjects during rest and two exercise levels. Signal memory in RRI sequences was
      estimated with autocorrelation, and probability density functions (PDFs) were
      created by fitting polynomial curves to the normalized histograms of the RRI
      sequences. The SIM generated fictive RRI sequences by randomly selecting RRI
      values from a PDF and integrating the series using parameters derived from the
      autocorrelation analysis. Fractal-scaling in the model RRI sequences was
      quantified with detrended fluctuation analysis. After optimizing the model with
      the autocorrelation-based and PDF parameters, the SIM was able to produce fictive
      RRI sequences with significant fractal scaling (statistically assessed with
      surrogate analysis, p <; 0.001), and with fractal-scaling characteristics similar
      to the original human data (p = 0.62). Increasing the length of the SIM-generated
      sequences did not alter the temporal scaling of the model sequences. In
      conclusion, this research demonstrated a stochastic and integrative model that
      can replicate the temporally correlated characteristics of the human heart rate.

PMID- 29060561
TI  - Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) effects on
      autonomic outflow in hypertension.
AB  - Transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN) has
      been proposed as a non-invasive alternative to vagus nerve stimulation (VNS).
      However, its cardiovagal effects are inconsistent across studies, likely due to
      inhomogeneity in the stimulation parameters. Here, we evaluate respiratory-gated
      ABVN stimulation (Respiratory-gated Auricular Vagal Afferent Nerve Stimulation,
      RAVANS), where the stimuli are delivered in 1 s bursts during the exhalation
      phase of respiration, thus mimicking the breathing-induced modulation of cardiac
      vagal activity. In this study, we present preliminary results from an ongoing
      single-arm, open label trial investigating the effects of different intensities
      of RAVANS in hypertensive subjects. We found that a mid-intensity RAVANS
      stimulation (rated as a 5 on a 0-10 scale) increases the cardiovagal tone and
      reduces the sympathetic tone during a paced breathing task. The present results
      could contribute to optimize RAVANS as a non-invasive, low-cost therapeutic
      intervention for hypertension.

PMID- 29060560
TI  - Towards the identification of subjects prone to develop atrial fibrillation after
      coronary artery bypass graft surgery via univariate and multivariate complexity
      analysis of heart period variability.
AB  - The assessment of cardiovascular control complexity as derived from spontaneous
      heart period (HP) fluctuations can be improved by exploiting a multivariate (MV)
      approach. This work proposes the assessment of a normalized complexity index
      (NCI) of HP variability according to a k-nearest-neighbor approach based on local
      predictability performed in a MV nonuniform embedding space. The method allows
      the selection of the past components of HP, systolic arterial pressure (SAP) and
      respiration (R) most useful for the prediction of HP fluctuations. The NCI
      derived from the MV approach (NCIMV) was compared to a NCI computed via the same
      technique applied in a univariate (UV) embedding space (NCIUV) formed exclusively
      by HP past samples. Indexes were computed in 130 patients undergoing coronary
      artery bypass graft (CABG) surgery before and after the induction of general
      anesthesia. Thirty-eight subjects developed atrial fibrillation (AF) after
      surgery, while the remaining ones did not (noAF, n=92). Both NCIUV and NCIMV
      could separate AF from noAF patients and revealed a larger complexity of the AF
      subjects. However, the statistical power of the NCIMV was superior given that the
      probability of type I error was smaller than that of NCIUV. The assessment of
      cardiac control complexity could improve risk stratification of patients at risk
      of developing AF after CABG surgery.

PMID- 29060562
TI  - Multiscale sample entropy of heart rate and blood pressure: Methodological
      aspects.
AB  - The entropy of heart rate variability is one of the main features characterizing
      the complexity of the cardiovascular system. In order to take into account the
      multiscale nature of cardiovascular regulation, it was proposed to evaluate
      entropy with a multiscale approach, based on the estimation of Sample Entropy on
      progressively coarse-grained series (Multiscale Sample Entropy, MSE). Aim of this
      work is to investigate two methodological aspects related to MSE of
      cardiovascular signals. The first aspect regards the tolerance below which a
      couple of points are considered similar in a given embedding dimension, in
      particular how the way the tolerance is set at each level of coarse graining
      influences the MSE estimates. The second aspect regards whether heart rate and
      blood pressure (BP) signals are characterized by different MSE structures.To
      investigate these aspects, we analyzed 65 continuous BP recordings of more than
      90-minute duration in healthy volunteers sitting at rest, and applied MSE
      estimators to beat-by-beat series of systolic BP, diastolic BP and pulse interval
      (inverse of heart rate). Results indicate that the way the tolerance is set
      during coarse graining influences substantially the MSE profile of cardiovascular
      signals, modifying the relative level of their unpredictability.

PMID- 29060563
TI  - Computer-aided detection for prostate cancer detection based on multi-parametric
      magnetic resonance imaging.
AB  - Prostate cancer (CaP) is the second most diagnosed cancer in men all over the
      world. In the last decades, new imaging techniques based on magnetic resonance
      imaging (MRI) have been developed improving diagnosis. In practice, diagnosis is
      affected by multiple factors such as observer variability and visibility and
      complexity of the lesions. In this regard, computer-aided detection and diagnosis
      (CAD) systems are being designed to help radiologists in their clinical practice.
      We propose a CAD system taking advantage of all MRI modalities (i.e., T2-W-MRI,
      DCE-MRI, diffusion weighted (DW)-MRI, MRSI). The aim of this CAD system was to
      provide a probabilistic map of cancer location in the prostate. We extensively
      tested our proposed CAD using different fusion approaches to combine the features
      provided by each modality. The source code and the dataset have been released.

PMID- 29060564
TI  - Detecting impaired vision caused by AMD from gaze data.
AB  - Age Related Macular Degeneration (AMD) is the third leading cause of blindness
      and the first one in the elderly. AMD usually causes central blindness due to
      loss of photoreceptor cell . In this paper, we propose to detect AMD caused
      vision impairment from gaze data. Compared with the current methods, e.g., Amsler
      grid, Microperimetry and Preferential Hyperacuity Perimetry, to detect vision
      impairments, the proposed method has several advantages. 1) It does not require
      the patient to stare at a fixed position throughout the test. 2) It does not
      require the patient to orally or manually report / mark out the vision
      impairment. 3) It is easy to operate thus a trained nurse is capable of operating
      the test. We collect gaze data while the patient is performing fixation and
      smooth pursuit. Features describing the gaze properties are extracted and SVM
      with linear kernel is trained to detect AMD impaired vision. To implement the
      proposed method, we collected gaze data of 74 eyes of 57 patients, who are
      diagnosed as AMD patient by clinicians. Nidek Microperimetry is adopted as gold
      standard. 57 eyes with normal vision and 17 eyes with impaired vision (blind at
      more than half test points in Nidek test) are used for test. The result verifies
      the effectiveness of detecting vision impairment from gaze data.

PMID- 29060565
TI  - Gabor-based automatic spinal level identification in ultrasound.
AB  - This paper presents an automatic lumbar spine level identification system based
      on image processing of ultrasound images. The goal is to aid anesthetists in
      identifying the correct spinal level during epidural anesthesia. Spine level
      identification is initiated by detecting the location of the sacrum using a
      classifier based on a support vector machine. Image stitching is then conducted
      to produce a panorama image of the spinal area. During this process, the location
      of spinal processes are enhanced using a Gabor filter and detected through
      template matching. The locations of the spinal processes are tracked and used as
      an overlay on the ultrasound image in real-time. The system then informs the
      anesthetists when the correct spinal level has been reached. The system was
      evaluated on forty volunteers by two anesthetists with varying experience level
      and was able to detect the correct position of the L3-L4 spinal level in all of
      the volunteers. The average time taken to produce the location of the L3-L4
      spinal level was 30.92 seconds. The results show that the system can quickly and
      accurately detect the location of the target spinal level.

PMID- 29060566
TI  - Image recognition with missing-features based on gaussian mixture model and graph
      constrained nonnegative matrix factorization.
AB  - The demand for automatically recognizing medical images for screening, reference
      and management is growing faster than ever. Missing data phenomenon in medical
      image applications is common existence, and it could be inevitable. In this
      paper, we have addressed the problem of recognizing medical images with missing
      features via Gaussian mixture model (GMM)-based approach. Since training a GMM by
      directly using high-dimensional feature vectors will result in instability, we
      have proposed a novel strategy to train the GMM from the corresponding reduced
      dimensional one. The proposed method contains training and test phases. The
      former contains feature extraction, graph constrained nonnegative matrix
      factorization (NMF), GMM training, and the alternating expectation conditional
      maximization (AECM) for extending the reduced-dimensional GMM. In test phase, two
      methods, marginalizing GMM using Bayesian decision (MGBD) and conditional mean
      imputation (CMI), are applied to impute missing-features. Posterior probability
      of test images is calculated to identify objects. Experimental results on three
      real datasets demonstrate the feasibility and efficiency of the proposed scheme.

PMID- 29060567
TI  - Gastrointestinal bleeding detection in wireless capsule endoscopy images using
      handcrafted and CNN features.
AB  - Gastrointestinal (GI) bleeding detection plays an essential role in wireless
      capsule endoscopy (WCE) examination. In this paper, we present a new approach for
      WCE bleeding detection that combines handcrafted (HC) features and convolutional
      neural network (CNN) features. Compared with our previous work, a smaller-scale
      CNN architecture is constructed to lower the computational cost. In experiments,
      we show that the proposed strategy is highly capable when training data is
      limited, and yields comparable or better results than the latest methods.

PMID- 29060568
TI  - Automated angiodysplasia detection from wireless capsule endoscopy.
AB  - We present a novel system for the automatic detection of angiodysplasia lesions
      from capsule endoscopy images. The approach identifies potential regions of
      interest and classifies them using a combination of color-based, texture,
      statistical and morphological features. A boosted decision tree classification
      method is used in order to overcome the problem of unbalanced sampling between
      pathological and non-pathological regions. The lesion detection method has been
      designed and validated using a lesion database labelled by an expert. The
      approach achieves a sensitivity of 89.51% and a specificity of 96.8%, thus
      providing a high performance in the detection of angiodysplasia lesions.

PMID- 29060569
TI  - Intracardiac electrogram envelope detection during atrial fibrillation using fast
      orthogonal search.
AB  - The performance of any intracardiac electrogram processing method is limited by
      the accuracy of its activation detection approach. The most common activation
      detection approaches in the literature aim to find the highest peak in the
      activation envelope disregarding the start and end points. However, the duration
      of the activation can be used to extract useful information such as wave
      collisions. In this work, we propose a novel orthogonal based approach for fast
      and accurate estimation of the start and end of the activations (activation
      envelope) in intracardiac recordings during atrial fibrillation. Wavelet
      decomposition of the signals was used to create a pool of basis functions for the
      proposed modeling method. The database included 24 recordings of approximate
      length of 6s obtained from atrial endocardium of 5 patients who underwent
      catheter ablation therapy. The start and end of activations in each electrogram
      was manually annotated by an expert electrophysiologist and the annotations were
      used as a gold standard to calculate the performance of our envelope detection
      method. The results show promising performance and excellent robustness to
      training data for our proposed method with respect to envelope estimation error.

PMID- 29060570
TI  - Statistical baseline assessment in cardiotocography.
AB  - Cardiotocography (CTG) is the most common non-invasive diagnostic technique to
      evaluate fetal well-being. It consists in the recording of fetal heart rate (FHR;
      bpm) and maternal uterine contractions. Among the main parameters characterizing
      FHR, baseline (BL) is fundamental to determine fetal hypoxia and distress. In
      computerized applications, BL is typically computed as mean FHR+/-DeltaFHR, with
      DeltaFHR=8 bpm or DeltaFHR=10 bpm, both values being experimentally fixed. In
      this context, the present work aims: to propose a statistical procedure for
      DeltaFHR assessment; to quantitatively determine DeltaFHR value by applying such
      procedure to clinical data; and to compare the statistically-determined DeltaFHR
      value against the experimentally-determined DeltaFHR values. To these aims, the
      552 recordings of the "CTU-UHB intrapartum CTG database" from Physionet were
      submitted to an automatic procedure, which consisted in a FHR preprocessing phase
      and a statistical BL assessment. During preprocessing, FHR time series were
      divided into 20-min sliding windows, in which missing data were removed by linear
      interpolation. Only windows with a correction rate lower than 10% were further
      processed for BL assessment, according to which DeltaFHR was computed as FHR
      standard deviation. Total number of accepted windows was 1192 (38.5%) over 383
      recordings (69.4%) with at least an accepted window. Statistically-determined
      DeltaFHR value was 9.7 bpm. Such value was statistically different from 8 bpm
      (P<;10-19) but not from 10 bpm (P=0.16). Thus, DeltaFHR=10 bpm is preferable over
      8 bpm because both experimentally and statistically validated.

PMID- 29060571
TI  - Nonlinear analysis of heart rate variability for the assessment of Dysphoria.
AB  - Dysphoric patients show symptoms associated with Major Depression, although
      within a narrowed symptomatology spectrum. In prevailing practice, clinicians
      assess Dysphoria through psychological scores and questionnaires exclusively,
      therefore without taking into account objective biomarkers. In this study, we
      investigated heartbeat linear and nonlinear dynamics aiming to an objective
      assessment of Dysphoria. To this end, we derived standard and nonlinear measures
      from heart rate variability (HRV) series gathered from dysphoric (n=14) and
      nondysphoric (n=17) undergraduate students during 5 minutes of resting state. We
      performed both statistical and pattern recognition analyses in order to discern
      the two groups. Results showed significant group-wise differences in HRV
      nonlinear metrics exclusively, suggesting a crucial role of nonlinear sympatho
      vagal dynamics in Dysphoria. Furthermore, we achieved a classification accuracy
      of 77.52% for the automatic identification of Dysphoria at a single-subject
      level.

PMID- 29060572
TI  - Classification enhancement for post-stroke dementia using fuzzy neighborhood
      preserving analysis with QR-decomposition.
AB  - The aim of the present study was to discriminate the electroencephalogram (EEG)
      of 5 patients with vascular dementia (VaD), 15 patients with stroke-related mild
      cognitive impairment (MCI), and 15 control normal subjects during a working
      memory (WM) task. We used independent component analysis (ICA) and wavelet
      transform (WT) as a hybrid preprocessing approach for EEG artifact removal. Three
      different features were extracted from the cleaned EEG signals: spectral entropy
      (SpecEn), permutation entropy (PerEn) and Tsallis entropy (TsEn). Two
      classification schemes were applied - support vector machine (SVM) and k-nearest
      neighbors (kNN) - with fuzzy neighborhood preserving analysis with QR
      decomposition (FNPAQR) as a dimensionality reduction technique. The FNPAQR
      dimensionality reduction technique increased the SVM classification accuracy from
      82.22% to 90.37% and from 82.6% to 86.67% for kNN. These results suggest that
      FNPAQR consistently improves the discrimination of VaD, MCI patients and control
      normal subjects and it could be a useful feature selection to help the
      identification of patients with VaD and MCI.

PMID- 29060573
TI  - Attenuation of vagal modulation with aging: Univariate and bivariate analysis of
      HRV.
AB  - The aging process leads to diverse changes in the human organism, including in
      autonomic system modulation. In this study, we calculated indices of HRV in
      frequency (power spectral density, PSD) and time (the impulse response (IR)
      method) domains, using data from healthy young and elderly volunteers (Fantasia
      database from Physionet). The results obtained showed that aging leads to an
      attenuation of vagal modulation of elderly individuals when compared to young
      volunteers.

PMID- 29060574
TI  - Multiscale dispersion entropy for the regional analysis of resting-state
      magnetoencephalogram complexity in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive and irreversible brain disorder of the
      nervous system affecting memory, thinking, and emotion. It is the most important
      cause of dementia and an influential social problem in all the world. The
      complexity of brain recordings has been successfully used to help to characterize
      AD. We have recently introduced multiscale dispersion entropy (MDE) as a very
      fast and powerful tool to quantify the complexity of signals. The aim of this
      study is to assess the ability of MDE, in comparison with multiscale permutation
      entropy (MPE) and multiscale entropy (MSE), to discriminate 36 AD patients from
      26 elderly age-matched control subjects using resting-state magnetoencephalogram
      (MEG) recordings. The results showed that MDE, unlike MSE, does not lead to
      undefined values. Moreover, the differences between the MDE values for AD
      palatines versus controls were more significant than their corresponding MSE- and
      MPE-based values. In addition, the computation time for our recently developed
      MDE was considerably less than that for MSE and even MPE.

PMID- 29060575
TI  - Gait variability assessment in neuro-degenerative patients by measuring
      complexity of independent sources.
AB  - Patients suffering from neuro-degenerative diseases have difficulties with normal
      locomotion. This problem progresses with the course of disease. Gait assessment
      is an effective way of diagnosing the disease and quantifying its progress which
      can effectively prevent falls. In this paper, an automatic assessment method for
      analyzing gait data obtained by force sensor insoles is introduced. The gait
      analysis method is based on measuring the complexity of gait data after
      extracting independent sources. The results are promising an average accuracy of
      94% for three different diseases.

PMID- 29060576
TI  - Complexity analysis of resting state fMRI signals in depressive patients.
AB  - Analysis of brain signal complexity reveals the intrinsic network dynamics and is
      widely utilized in the investigation of mechanisms in mental disorders. In this
      study, the complexity of resting-state functional magnetic resonance imaging
      (fMRI) signals was explored in patients with depression using multiscale entropy
      (MSE). Thirty-five patients diagnosed with depression and 22 age- and gender
      matched healthy controls were considered. The MSE profiles in five brain networks
      of the two participant groups were evaluated and analyzed. The results showed
      that depressive patients exhibited higher complexity in the left frontoparietal
      network than that seen in healthy controls, which is known to be critical for
      executive control functions. Through this study, the efficacy of MSE in
      identifying and understanding the mental disorders was also demonstrated.

PMID- 29060577
TI  - Predicting learning dynamics in Multiple-Choice Decision-Making Tasks using a
      variational Bayes technique.
AB  - Multiple-Choice Decision-Making Tasks are widely used to analyze behavior and
      infer underlying cognitive states that shape the decision and learning processes.
      The behavioral signals recorded in these tasks are dynamic and often non-Gaussian
      - for instance, when learning a multiple choice association task. Previously
      developed estimation algorithms for latent behavioral variables do not address
      multiple-choice responses. In this research, we use a state-space modeling
      framework to predict a cognitive learning state related to multiple choice
      decisions, which are best described by a multinomial distribution. The proposed
      algorithm combines a multinomial filter/smoother and a variational Bayes
      technique to estimate the dynamics of a learning state vector. The algorithm is
      applied to decision response data recorded from non-human primates (NHPs)
      performing a Multiple-Choice Decision Task.

PMID- 29060578
TI  - A closed-form unsupervised geometry-aware dimensionality reduction method in the
      Riemannian Manifold of SPD matrices.
AB  - Riemannian geometry has been found accurate and robust for classifying
      multidimensional data, for instance, in brain-computer interfaces based on
      electroencephalography. Given a number of data points on the manifold of
      symmetric positive-definite matrices, it is often of interest to embed these
      points in a manifold of smaller dimension. This is necessary for large dimensions
      in order to preserve accuracy and useful in general to speed up computations.
      Geometry-aware methods try to accomplish this task while respecting as much as
      possible the geometry of the original data points. We provide a closed-form
      solution for this problem in a fully unsupervised setting. Through the analysis
      of three brain-computer interface data bases we show that our method allows
      substantial dimensionality reduction without affecting the classification
      accuracy.

PMID- 29060579
TI  - Real-time physiological tremor estimation using recursive singular spectrum
      analysis.
AB  - Physiological hand tremor causes undesirable vibration of hand-held surgical
      instruments which results in imprecisions and poor surgical outcomes. Existing
      tremor cancellation algorithms are based on detection of the tremulous component
      from the whole motion; then adding an anti-phase tremor signal to the whole
      motion to cancel it out. These techniques are based on adaptive filtering
      algorithms which need a reference signal that is highly correlated with the
      actual tremor signal. Hence, such adaptive approaches use a non-linear phase
      filter to pre-filter the tremor signal either offline or in real-time. However,
      pre-filtering causes unnecessary delays and non-linear phase distortions as the
      filter has frequency selective delays. Consequently, the anti-phase tremor signal
      cannot be generated accurately which results in poor tremor cancellation. In this
      paper, we present a new technique based on singular spectrum analysis (SSA) and
      its recursive version, that is, recursive singular spectrum analysis (RSSA).
      These algorithms decompose the whole motion into dominant voluntary components
      corresponding to larger eigenvalues and oscillatory tremor components having
      smaller eigenvalues. By selecting a group of specific decomposed signals based on
      their eigenvalues and spectral range, both voluntary and tremor signals can be
      reconstructed accurately. We test the SSA and RSSA algorithms using recorded
      tremor data from five novice subjects. This new approach shows the tremor signal
      can be estimated from the whole motion with an accuracy of up to 85% offline. In
      real-time, tolerating a delay of ~ 72ms, the tremor signal can be estimated with
      at least 70% accuracy. This delay is found to be one-tenth of the delay caused by
      a conventional linear-phase bandpass filter to achieve similar performance in
      real-time.

PMID- 29060580
TI  - Integrating channel selection and feature selection in a real time epileptic
      seizure detection system.
AB  - Automated real time seizure detection is difficult since detection sensitivity,
      false detection rate and seizure onset detection latency need to be considered
      simultaneously. Traditional pattern recognition and classification system usually
      suffers huge performance variation due to patient specificity and algorithm
      inadaptability. To address this problem, we propose a two stage seizure detection
      system which integrates off-line channel selection and feature selection before
      the construction of the final model. This system allows patient specific channel
      selection and flexible feature set extraction for individual patient, so that a
      more compact and reliable model could be developed. Employing the two stage
      scheme not only decreases hardware cost in signal readout and feature extraction,
      but also remarkably improves detection sensitivity and reduces false detections.
      Mutual information based method is used for channel selection, while Random
      Forests and nonlinear SVM-RFE are evaluated for feature selection. The whole
      system achieves a mean detection latency of 6 seconds and a false detection rate
      of 0.356 per hour. Based on the test dataset, the sensitivity is found to 74.2%
      by sample or 98.4% by record with only two detection misses. Our design is also
      hardware-friendly, which could be implemented as a single chip closed loop neural
      modulation system.

PMID- 29060581
TI  - Evidence of brain functional deficits following sport-related mild traumatic
      brain injury.
AB  - Sport related mild traumatic brain injury (mTBI), generally known as a
      concussion, is a worldwide critical public health concern nowadays. Despite
      growing concern emphasized by scientific research and recent media presentation
      regarding mTBI and its effect in athletics life, the management, and prevention
      of mTBI are still not properly done. The evaluation mainly hampered due to the
      lack of proper knowledge, subjective nature of assessment tools including the
      fact that the brain functional deficits after mTBI can be mild or hidden. As a
      result, development of an effective tool for proper management of these mild
      incidents is a subject of active research. In this paper, to examine the neural
      substrates following mTBI, an analysis based on electroencephalogram (EEG) from
      twenty control and twenty concussed athletes is presented. Preliminary results
      suggest that the concussed athletes have a significant increase in delta, theta
      and alpha power but a decrease in beta power. We also calculated the power for
      individual frequencies from 1 Hz to 40 Hz in order to find out the specific
      frequencies with the highest deficits. The significant deficiencies were found at
      1-2 Hz of delta band, 6-7 Hz of theta band, 8-10 Hz of the alpha band, and 16-18
      Hz and 24-29 Hz of the beta band. Though there was no significant difference as
      observed in gamma band, we found the deficit was significant at 34-36 Hz range
      within the gamma band. The observed deficits at various frequencies demonstrate
      that even if there is no significant difference in the traditional frequency
      bands, there may be hidden deficits at some specific frequencies within a
      frequency band. These preliminary results suggest that the EEG analysis at each
      unity frequency may be more promising means of identifying the neuronal damage
      than the traditional frequency band based analysis. Eventually, the proposed
      analysis can provide an improved approximation to monitor the pathophysiological
      recovery after a concussion.

PMID- 29060582
TI  - Estimating unmeasured invasive EEG signals using a reduced-order observer.
AB  - Epilepsy affects around 50 million people worldwide. Over 30% of patients are
      drug-resistant where the only treatment may be surgical resection of the
      epileptogenic zone (EZ), the region of the brain that generates seizures.
      Identification of the EZ is often based on invasive EEG recordings. As such,
      surgical outcome relies heavily on precise and dense placement of EEG electrodes
      into the brain. Despite large brain regions being removed, success rates barely
      reach 65%. This gives rise to the "missing electrode problem", where clinicians
      want to know what neural activity looks like between sparsely implanted
      electrodes. Solving this problem will enable more accurate localization of the
      EZ. In this paper, we demonstrate the first steps towards developing a
      computational platform to estimate neural activity at the "missing electrodes"
      using a reduced-order observer from control theory. Specifically, we constructed
      a sequence of discrete time Linear Time-Invariant (LTI) models using the
      available EEG data from two epilepsy patients. Then, we used the models to
      simulate EEG data and remove selected signals ("missing" states) from the
      simulated data set. Finally, we used a reduced-order observer to estimate the
      signals of these "missing" states and evaluated performance by comparing the
      observer estimates to the simulated EEG time series.

PMID- 29060583
TI  - A mental fatigue index based on regression using mulitband EEG features with
      application in simulated driving.
AB  - Development of accurate fatigue level prediction models is of great importance
      for driving safety. In parallel, a limited number of sensors is a prerequisite
      for development of applicable wearable devices. Several EEG-based studies so far
      have performed classification in two or few levels, while others have proposed
      indices based on power ratios. Here, we utilized a regression Random Forest model
      in order to provide more accurate continuous fatigue level prediction. In detail,
      multiband power features were extracted from EEG data recorded from one hour
      simulated driving task. Next, cross-subject regression was performed to obtain
      common fatigue-related discriminative features. We achieved satisfactory
      prediction accuracy and simultaneously we minimized required electrodes,
      proposing to use a set of 3 electrodes.

PMID- 29060584
TI  - Decoding brain cognitive activity across subjects using multimodal M/EEG
      neuroimaging.
AB  - Brain decoding is essential in understanding where and how information is encoded
      inside the brain. Existing literature has shown that a good classification
      accuracy is achievable in decoding for single subjects, but multi-subject
      classification has proven difficult due to the inter-subject variability. In this
      paper, multi-modal neuroimaging was used to improve two-class multi-subject
      classification accuracy in a cognitive task of differentiating between a face and
      a scrambled face. In this transfer learning problem, a feature space based on
      special-form covariance matrices manipulated with riemannian geometry are used. A
      supervised two-layer hierarchical model was trained iteratively for estimating
      classification accuracies. Results are reported on a publically available multi
      subject, multi-modal human neuroimaging dataset from MRC Cognition and Brain
      Sciences Unit, University of Cambridge. The dataset contains simultaneous
      recordings of electroencephalography (EEG) and magnetoencephalography (MEG). Our
      model attained, using leave-one-subject-out cross-validation, a classification
      accuracy of 70.82% for single modal EEG, 81.55% for single modal MEG and 84.98%
      for multi-modal M/EEG.

PMID- 29060585
TI  - EEG-based Approach-Withdrawal index for the pleasantness evaluation during taste
      experience in realistic settings.
AB  - The taste is a vital sense in humans, because of its active role in regulating
      nutrition or avoiding harmful substances. Several studies showed the important
      role of the brain Pre-Frontal Cortex in decoding information coming from the
      gustatory system. It is also widely known, in neuroscientific literature, that
      the asymmetry of Pre-Frontal Cortex Activity is closely linked to the feeling of
      pleasantness experienced by the subject during sensorial stimulation. In this
      regard, from the electroencephalographic (EEG) signal it is possible to estimate
      the Approach/Withdrawal (AW) index, which has been largely investigated and
      validated in scientific literature, regarding visual, acoustic and olfactory
      stimuli.

PMID- 29060586
TI  - Multimodal Ultrasound imaging based diagnosis of liver cancers with a two-stage
      multi-view learning framework.
AB  - Computer-aided diagnosis (CAD) of liver cancers on contrast-enhanced ultrasound
      (CEUS) has attracted considerable attention in recent years. The enhancement
      patterns on CEUS for liver lesions consist of the arterial, portal venous and
      late phases. Several typical images selected from these three phases can provide
      reliable information basis for diagnosis of liver lesions. Therefore, we propose
      to develop a CAD framework for liver cancers with only one B-mode image and three
      typical CEUS images selected from three enhancement patterns, which simulates the
      clinical diagnosis mode of radiologists. Moreover, a framework of two-stage multi
      view learning (TS-MVL) is proposed to perform both feature-level and classifier
      level MVL for the diagnosis of liver cancers with multimodal ultrasound images.
      We propose to apply the nonlinear kernel matrix (NKM) algorithm to effectively
      fuse the features of multimodal ultrasound images, and then perform the multiple
      kernel boosting (MKB) algorithm to promote the predictive performance of multiple
      classifiers according to multi-view features. The experimental results indicate
      that the proposed algorithm outperforms the commonly used multi-view learning
      algorithms.

PMID- 29060587
TI  - Myocardial elastogram using a fast mapping algorithm.
AB  - Ultrasound myocardial elastography is a promising technique to estimate regional
      myocardial function. In this study, we proposed a fast mapping method to map
      myocardial elastogram. A nude mouse's heart was scanned in supine position by an
      ultrasound system. The parasternal long-axis view of the heart and the ultrasound
      radio frequency (RF) signals were acquired for dynamic estimation of myocardial
      elasticity. The displacement and strain were calculated using analytic
      minimization (AM) and linear polynomial curve fitting method, respectively. The
      fast mapping method was proposed to map myocardial elastogram. The results
      display the contraction of myocardium intuitively. The method in this study is
      proved to have a potential to estimate viable myocardium in the future.

PMID- 29060588
TI  - Image-guided laparoscopic pelvic lymph node dissection using stereo visual
      tracking free-hand laparoscopic ultrasound.
AB  - Laparoscopic pelvic lymph node dissection is a delicate operation because pelvic
      arteries, which should be located first to guide the dissection, are often
      concealed by tissues and cannot be identified in the endoscopic view.
      Consequently, arteries can be damaged if they are not located accurately. To
      improve dissection safety and efficiency, we have developed an image-guided
      navigation system to provide pelvic artery position information by registering a
      3D artery model extracted from CT images to a 3D model reconstructed from free
      hand laparoscopic ultrasound images. The ultrasound probe is tracked using a
      proposed stereo vision-based tracking strategy that can simplify the system and
      reduce setup time. The artery is segmented from 2D ultrasound images using a
      local phase-based snakes framework. The accuracy of the proposed navigation
      system was estimated in a phantom experiment (the TRE error was 1.58 +/- 0.70
      mm), and the feasibility of the proposed navigation system was confirmed in an
      animal experiment.

PMID- 29060589
TI  - Tracking large Anterior Mitral Leaflet displacements by incorporating optical
      flow in an active contours framework.
AB  - Echocardiography is an important tool to detect early evidence of mitral valve
      degradation associated with rheumatic heart disease. The segmentation and
      tracking of the Anterior Mitral Leaflet helps to quantify the morphologic valve
      anomalies, such as the leaflet thickening, shape and the mobility changes. The
      tracking of this leaflet throughout the cardiac cycle is still an open challenge
      in the research community. The widely used active contours segmentation framework
      fails when faced with large leaflet displacement. In this work, we propose the
      integration of optical flow in an open-ended active contour framework to address
      this difficulty. This additional information promotes solutions with contours
      next to high leaflet displacements, resulting in superior performance. The
      algorithm was tested on 9 fully annotated real clinical videos, acquired from the
      parasternal long axis view. The algorithm is compared with our previous work.
      Results show a clear improvement in situations where the leaflet exhibits large
      displacement or irregular shapes, with an average error of 4.5 pixels and a
      standard deviation of 2 pixels.

PMID- 29060590
TI  - Automatic initialization for active contour model in breast cancer detection
      utilizing conventional ultrasound and Color Doppler.
AB  - Regular examination of breasts may prevent and help to cure because breast cancer
      is treatable when it is detected early. Therefore, a breast cancer screening
      modality being sensitivity and cost-effective like ultrasonic imaging modality
      (US), is strongly required. In addition, the combination of a conventional US and
      its adjunct, Color Doppler has been proved for decreasing the rate of false
      positive in breast cancer diagnosis. Thus, combination of these imaging
      modalities in a breast cancer segmentation would provide some benefits as well.
      An effective method for feature segmentation, active contour model has been
      widely utilized for decades. A crucial stage that affects the performance of
      active contour model is the initialization. This paper proposes a novel method
      for an automatic initialization of active contour model designed specifically for
      US-based imaging modalities. The method estimates an initial contour by utilizing
      the fusion of conventional US and Color Doppler. Examples and comparisons with
      three state-of-the-art automatic initialization methods are demonstrated to
      present the advantages of the proposed method. The evaluation results show high
      accuracy of initialization as well as fast convergence to features of interest.

PMID- 29060591
TI  - 4D real-time phase-contrast flow MRI with sparse sampling.
AB  - Conventional phase-contrast (PC) MRI relies on electrocardiogram (ECG)
      synchronized cine acquisition and respiration control. It often results in
      relatively low data acquisition efficiency, and is unable to assess blood flow
      variabilities. Real-time imaging is a promising technique to overcome these
      limitations; however, it results in a challenging image reconstruction problem
      with highly-undersampled (k; t)-space data. This paper presents a novel model
      based imaging method, which integrates low-rank modeling with parallel imaging,
      to enable 4D real-time PC MRI without ECG gating and respiration control. The
      proposed method achieves an isotropic spatial resolution of 2.4 mm and temporal
      resolution of 35.2 ms, with three directional flow encodings. Moreover, it is
      able to resolve beat-by-beat flow variations, which cannot be achieved by the
      conventional cine-based approach. The proposed method was evaluated with in vivo
      experiments with one healthy subject and one arrhythmic patient. For the first
      time, we demonstrate the feasibility of 4D real-time PC MRI.

PMID- 29060592
TI  - Fast dictionary generation and searching for magnetic resonance fingerprinting.
AB  - A super-fast dictionary generation and searching (DGS) algorithm was developed
      for MR parameter quantification using magnetic resonance fingerprinting (MRF).
      MRF is a new technique for simultaneously quantifying multiple MR parameters
      using one temporally resolved MR scan. But it has a multiplicative computation
      complexity, resulting in a big burden of dictionary generating, saving, and
      retrieving, which can easily be intractable for any state-of-art computers. Based
      on retrospective analysis of the dictionary matching object function, a multi
      scale ZOOM like DGS algorithm, dubbed as MRF-ZOOM, was proposed. MRF ZOOM is
      quasi-parameter-separable so the multiplicative computation complexity is broken
      into additive one. Evaluations showed that MRF ZOOM was hundreds or thousands of
      times faster than the original MRF parameter quantification method even without
      counting the dictionary generation time in. Using real data, it yielded nearly
      the same results as produced by the original method. MRF ZOOM provides a super
      fast solution for MR parameter quantification.

PMID- 29060593
TI  - Parallel compressive sensing in a hybrid space: Application in interventional
      MRI.
AB  - Recently, susceptibility based positive contrast MRI technique emerged as an
      effective method of visualizing the small MR compatible devices, such as
      brachytherapy seeds. One of the challenges associated with this method is the
      long scan time. In this work, we present an accelerated susceptibility based
      positive contrast MR imaging method, in which the susceptibility map can be
      generated from an under-sampled data. We use a combination of parallel imaging
      (GRAPPA) and compressive sensing (CS) technique in a hybrid k-space. The results
      in brachytherapy seeds imaging show that 3-D high-quality images can be achieved
      at an acceleration factor up to 4, which can decrease the scan time from 4
      minutes to 1.4 minutes.

PMID- 29060594
TI  - Simultaneous multislice magnetic resonance fingerprinting with low-rank and
      subspace modeling.
AB  - Magnetic resonance fingerprinting (MRF) is a new quantitative imaging paradigm
      that enables simultaneous acquisition of multiple magnetic resonance tissue
      parameters (e.g., T1, T2, and spin density). Recently, MRF has been integrated
      with simultaneous multislice (SMS) acquisitions to enable volumetric imaging with
      faster scan time. In this paper, we present a new image reconstruction method
      based on low-rank and subspace modeling for improved SMS-MRF. Here the low-rank
      model exploits strong spatiotemporal correlation among contrast-weighted images,
      while the subspace model captures the temporal evolution of magnetization
      dynamics. With the proposed model, the image reconstruction problem is formulated
      as a convex optimization problem, for which we develop an algorithm based on
      variable splitting and the alternating direction method of multipliers. The
      performance of the proposed method has been evaluated by numerical experiments,
      and the results demonstrate that the proposed method leads to improved accuracy
      over the conventional approach. Practically, the proposed method has a potential
      to allow for a 3* speedup with minimal reconstruction error, resulting in less
      than 5 sec imaging time per slice.

PMID- 29060595
TI  - A low rank Hankel matrix reconstruction method for ultrafast magnetic resonance
      spectroscopy.
AB  - Magnetic resonance spectroscopy has many important applications in bio
      engineering while acquiring high dimensional spectroscopy is usually time
      consuming. Non-uniformly sampling can speed up the data acquisition but the
      missing data points have to be restored with proper signal models. In this work,
      a specific two dimensional (2D) magnetic resonance signal, in which the first
      dimension lies in frequency domain while the second dimension lies in time
      domain, is reconstructed with a proposed low rank Hankel-matrix method. This
      method explores two general properties: 1) the rank of a structured matrix,
      converted from a 2D exponential signal, is equal to the number of 2D spectral
      peaks; 2) this rank is small if the spectrum is sparse. Results on real magnetic
      resonance spectroscopy show that proposed method outperforms the state-of
      compressed sensing method on recovering low-intensity spectral peaks.

PMID- 29060596
TI  - Flexible wearable sensor nodes with solar energy harvesting.
AB  - Wearable sensor nodes have gained a lot of attention during the past few years as
      they can monitor and record people's physical parameters in real time. Wearable
      sensor nodes can promote healthy lifestyles and prevent the occurrence of
      potential illness or injuries. This paper presents a flexible wearable sensor
      system powered by an efficient solar energy harvesting technique. It can measure
      the subject's heartbeats using a photoplethysmography (PPG) sensor and perform
      activity monitoring using an accelerometer. The solar energy harvester adopts an
      output current based maximum power point tracking (MPPT) algorithm, which
      controls the solar panel to operate within its high output power range. The power
      consumption of the flexible sensor nodes has been investigated under different
      operation conditions. Experimental results demonstrate that wearable sensor nodes
      can work for more than 12 hours when they are powered by the solar energy
      harvester for 3 hours in the bright sunlight.

PMID- 29060597
TI  - Comparison of hand-craft feature based SVM and CNN based deep learning framework
      for automatic polyp classification.
AB  - Colonoscopy is a standard method for screening polyps by highly trained
      physicians. Miss-detected polyps in colonoscopy are potential risk factor for
      colorectal cancer. In this study, we investigate an automatic polyp
      classification framework. We aim to compare two different approaches named hand
      craft feature method and convolutional neural network (CNN) based deep learning
      method. Combined shape and color features are used for hand craft feature
      extraction and support vector machine (SVM) method is adopted for classification.
      For CNN approach, three convolution and pooling based deep learning framework is
      used for classification purpose. The proposed framework is evaluated using three
      public polyp databases. From the experimental results, we have shown that the CNN
      based deep learning framework shows better classification performance than the
      hand-craft feature based methods. It achieves over 90% of classification
      accuracy, sensitivity, specificity and precision.

PMID- 29060598
TI  - A wearable autonomous heart rate sensor based on piezoelectric-charge-gated thin
      film transistor for continuous multi-point monitoring.
AB  - Autonomous wearable biomedical sensors enable continuous human body vital signs
      monitoring with features such as being conformable, mobile, cost-effective and
      self-powered. In this work, we report on an autonomous and multi-positional
      sensor capable of heart rate and blood pressure monitoring. The device concept is
      based on a piezoelectric-charge-gated thin-film transistor (PCGTFT) where a
      polyvinylidene fluoride (PVDF) piezoelectric sandwich structure is incorporated
      with an amorphous silicon (a-Si:H) dual-gate TFT (DGTFT). An analytical model and
      preliminary experimental results will be presented along with a demonstration of
      a proof-of-concept sensing system for continuous multi-point heart rate
      monitoring.

PMID- 29060599
TI  - Low group delay signal conditioning for wearable central blood pressure
      monitoring device.
AB  - Pulse transit time (ptt) is a widely researched approach for wearable,
      unobtrusive, blood pressure monitoring. The estimation of ptt, being a delay
      measurement, may be affected by the group delay introduced by the signal
      conditioning chain. In this work a previously reported method for estimating
      central (aortic) blood pressure from ptt at aortic domain, using ECG R wave and
      BCG J wave detection, is considered. A simple design approach for the signal
      conditioning chain, which is suitable for a wearable device and that takes care
      of minimizing the impact of eventually introduced spurious delays is presented.
      The design provides less than 2ms group-delay. The design of a wearable device
      prototype for ECG, BCG and ptt acquisition and experimental results of its
      application are reported, showing the effectiveness of the proposed approach.

PMID- 29060600
TI  - Hemodynamic sensing of 3D fingertip force using PPG device on proximal part.
AB  - This research proposed a novel method to estimate the 3D contact force of a
      fingertip using a photoplethysmogram (PPG) device on the proximal part of a
      finger. The proposed method detects non-pulsatile and pulsatile components of PPG
      signals, extracts eight feature values related to the contact force, and
      estimates the force by multiple linear regression. In the validation experiments,
      the participants wore a PPG device at the proximal part of the index finger and
      applied contact force. Then, the relationship between the contact force and PPG
      feature values was investigated. As a result, the system was found to be capable
      of estimating the 3D contact force with a root-mean-square error of 3.5 % of the
      maximum contact force.

PMID- 29060601
TI  - Tarsusmeter: Development of a wearable device for ankle joint impedance
      estimation.
AB  - We present the development and basic evaluation of a new wearable device for
      estimation of ankle joint impedance called Tarsusmeter. The device is intended
      for application with persons with locomotion disabilities to quantify the ankle
      joint impedance, especially in cases of spasticity where the joint's impedance is
      expected to differ significantly from healthy persons. The lack of a simple and
      light weight solution to provide objective evaluation of ankle joint impedance
      motivates the design criteria of this device to be as such. The target
      application is also to quantify variable stiffness actuator based orthosis in
      vivo. Thus the form factor avoids overlap with custom shapes of such orthosis.
      The paper presents the mechanical design of the device, physical simulations to
      characterize the device-leg system, the used algorithm for impedance parameter
      estimation, and preliminary testing of the device.

PMID- 29060602
TI  - Development of a smartphone-based pulse oximeter with adaptive SNR/power
      balancing.
AB  - Millions worldwide suffer from diseases that exhibit early warnings signs that
      can be detected by standard clinical-grade diagnostic tools. Unfortunately, such
      tools are often prohibitively expensive to the developing world leading to
      inadequate healthcare and high mortality rates. To address this problem, a
      smartphone-based pulse oximeter is presented that interfaces with the phone
      through the audio jack, enabling point-of-care measurements of heart rate (HR)
      and oxygen saturation (SpO2). The device is designed to utilize existing phone
      resources (e.g., the processor, battery, and memory) resulting in a more portable
      and inexpensive diagnostic tool than standalone equivalents. By adaptively tuning
      the LED driving signal, the device is less dependent on phone-specific audio jack
      properties than prior audio jack-based work making it universally compatible with
      all smartphones. We demonstrate that the pulse oximeter can adaptively optimize
      the signal-to-noise ratio (SNR) within the power constraints of a mobile phone
      (<; 10mW) while maintaining high accuracy (HR error <; 3.4% and SpO2 error <;
      3.7%) against a clinical grade instrument.

PMID- 29060603
TI  - Measurement of heartbeat intervals in a sitting position using multiple
      piezoelectric sensors with body movement reduction.
AB  - In this study, we proposed a measurement system that extracts heartbeat interval
      data from multiple piezoelectric sensors placed on a chair that eliminates noise
      generated by body movement. We asked five healthy males (21-24 years old) to sit
      in an arbitrary position on a chair that had eight piezoelectric sensors
      attached, and heartbeat signals were measured. The experiment consisted of four
      measurements (5 min measurements after adequate rest), while performing specific
      body movements at a specific time, with deliberately mixed noise of body
      movements. To remove body movement noise, bandpass filter processing (4 Hz-20 Hz)
      was applied to the signal obtained from the piezoelectric sensors, and the
      heartbeat component was extracted using independent component analysis (number of
      separations was eight) on the processed waveform. For verification, the error
      rate was obtained before and after the removal of body movement noise,
      respectively. The error rate after removal of body motion was 2.91 +/- 0.75%. In
      our previous study with two piezoelectric sensors without body movement, the
      error rate was 2.47 +/- 2.66%. Therefore, our proposed measurement system may
      improve the accuracy of heartbeat interval detection, which can be observed
      continuously by removing the body motion.

PMID- 29060604
TI  - Dynamical brain connectivity estimation using GARCH models: An application to
      personality neuroscience.
AB  - It has recently become evident that the functional connectome of the human brain
      is a dynamical entity whose time evolution carries important information
      underpinning physiological brain function as well as its disease-related
      aberrations. While simple sliding window approaches have had some success in
      estimating dynamical brain connectivity in a functional MRI (fMRI) context, these
      methods suffer from limitations related to the arbitrary choice of window length
      and limited time resolution. Recently, Generalized autoregressive conditional
      heteroscedastic (GARCH) models have been employed to generate dynamical
      covariance models which can be applied to fMRI. Here, we employ a GARCH-based
      method (dynamic conditional correlation - DCC) to estimate dynamical brain
      connectivity in the Human Connectome Project (HCP) dataset and study how the
      dynamic functional connectivity behaviors related to personality as described by
      the five-factor model. Openness, a trait related to curiosity and creativity, is
      the only trait associated with significant differences in the amount of time
      variability (but not in absolute median connectivity) of several inter-network
      functional connections in the human brain. The DCC method offers a novel window
      to extract dynamical information which can aid in elucidating the
      neurophysiological underpinning of phenomena to which conventional static brain
      connectivity estimates are insensitive.

PMID- 29060605
TI  - Mapping the full vascular network in the mouse brain at submicrometer resolution.
AB  - Mapping the microvascular networks in the brain can lead to significant
      scientific and clinical insights. We developed a serial sectioning microscopy
      technique called the Knife-Edge Scanning Microscopy (KESM) to section and image
      the entire mouse brain at submicrometer resolution. In our effort to map the
      entire vascular network in the mouse brain, we perfused the vessels with India
      ink, and used KESM to image the prepared brain. This results in about 1.5 TB of
      raw image data which poses a serious challenge in terms of analysis. In this
      paper, we will present our data set, and computational algorithms we developed to
      trace and analyze morphological properties of the mouse brain vascular network.
      Since the data is available across the entire brain in full detail (the smallest
      capillaries can be observed in our data), it enables the comparison of regional
      differences in morphological properties. We expect our results to provide rich
      insights to brain and neuroscience researchers.

PMID- 29060606
TI  - Dynamic inter-network connectivity in the human brain.
AB  - Recently, the field of functional brain connectivity has shifted its attention on
      studying how functional connectivity (FC) between remote regions changes over
      time. It is becoming increasingly evident that the human "connectome" is a
      dynamical entity whose variations are effected over very short timescales and
      reflect crucial mechanisms which underline the physiological functioning of the
      brain. In this study, we employ ad-hoc statistical and surrogate data generation
      methods to quantify whether and which brain networks displayed dynamic behaviors
      in a very large sample of healthy subjects provided by the Human Connectome
      Project (HCP). Our findings provided evidences that there are specific pairs of
      networks and specific networks within the healthy brain that are more likely to
      display dynamic behaviors. This new set of findings supports the notion that
      studying the time-variant connectivity in the brain could reveal useful and
      important properties about brain functioning in health and disease.

PMID- 29060607
TI  - Resting-state brain correlates of cardiovascular complexity.
AB  - While estimates of complex heartbeat dynamics have provided effective prognostic
      and diagnostic markers for a wide range of pathologies, brain correlates of
      complex cardiac measures in general and of complex sympatho-vagal dynamics in
      particular are still unknown. In this study we combine resting state functional
      Magnetic Resonance Imaging (fMRI) and physiological signal acquisition from 34
      healthy subjects selected from the Human Connectome Project (HCP) repository with
      inhomogeneous point-process approximate and sample heartbeat entropy measures
      (ipApEn and ipSampEn) to investigate brain areas involved in complex
      cardiovascular control. Our results show that activity in the Temporal Gyrus,
      Frontal Orbital Cortex, Temporal Fusiform and Opercular cortices, Planum
      Temporale, and Paracingulate cortex are negatively correlated with ipApEn
      dynamics. Activity in the same cortical areas as well as in the Temporal Fusiform
      cortex are negatively correlated with ipSampEn dynamics. No significant positive
      correlations were found. These pioneering results suggest that cardiovascular
      complexity at rest is linked to a few specific cortical brain structures,
      including crucial areas connected with parasympathetic outflow. This corroborates
      the hypothesis of a multidimensional central network which controls nonlinear
      cardiac dynamics under a predominantly vagally-driven tone.

PMID- 29060608
TI  - Cognitive control related network analysis: A novel way to measure neuron fiber
      connection of Alzheimer's disease.
AB  - Effective measurement of cognitive impairment caused by Alzheimer's disease (AD)
      will provide a chance for early medical intervention and delay the disease onset.
      Diffusion tensor imaging (DTI) provides a non-intrusive examination of cranial
      nerve diseases which can help us observe the microstructure of neuron fibers.
      Cognitive control network (CCN) consists of the brain regions that highly related
      to human self-control. In this study, hub-and-spoke model which was widely used
      in transportation and sociology area had been employed to analyze the
      relationship of CCN and other regions under its control, cognitive control
      related network (CCRN) was built by applying this model. Local and global graph
      theoretical parameters were calculated and went through statistical analysis.
      Significant difference had been found in the scale of local as well as global
      which may represent the impairment of cognitive control ability. This result may
      provide a potential bio-marker for the loss of connection caused by Alzheimer's
      disease.

PMID- 29060609
TI  - Resting-state brain correlates of instantaneous autonomic outflow.
AB  - A prominent pathway of brain-heart interaction is represented by autonomic
      nervous system (ANS) heartbeat modulation. While within-brain resting state
      networks have been the object of intense functional Magnetic Resonance Imaging
      (fMRI) research, technological and methodological limitations have hampered
      research on the central correlates of cardiovascular control dynamics. Here we
      combine the high temporal and spatial resolution as well as data volume afforded
      by the Human Connectome Project with a probabilistic model of heartbeat dynamics
      to characterize central correlates of sympathetic and parasympathetic ANS
      activity at rest. We demonstrate an involvement of a number of brain regions such
      as the Insular cortex, Frontal Gyrus, Lateral Occipital Cortex, Paracingulate and
      Cingulate Gyrus and Precuneous Cortex, as well as subcortical structures
      (Thalamus, Putamen, Pallidum, Brain-Stem, Hippocampus, Amygdala, and Right
      Caudate) in the modulation of ANS-mediated cardiovascular control, possibly
      indicating a broader definition of the central autonomic network (CAN). Our
      findings provide a basis for an informed neurobiological interpretation of the
      numerous studies which employ HRV-related measures as standalone biomarkers in
      health and disease.

PMID- 29060610
TI  - A model study of the neural interaction via mutual coupling factor
      identification.
AB  - In this paper, an extension of the Hodgkin-Huxley model has been presented to
      describe the interaction between the nerve fibres. Based on the equivalent
      electrical circuit, the conductance per unit area between two coupled axons has
      been introduced as the pairwise coupling factors. Based on the measurement of the
      membrane potential, these coupling factors can be estimated by linearised
      identification methods. Therefore, the axon-to-axon interaction can be
      characterized, which improves the accuracy of the models. Comparing with the
      simulation studies of the mechanistic model, the presented model is more
      convenient to be analyzed while the computational complexity has been reduced.
      Using the presented description, the simulation results indicate that the
      presented model and the analysis strategy are effective.

PMID- 29060611
TI  - On electrophysiological signal complexity during biological neuronal network
      development and maturation.
AB  - Developing neuronal populations are assumed to increase their synaptic
      interactions and generate synchronized activity, such as bursting, during
      maturation. These effects may arise from increasing interactions of neuronal
      populations and increasing simultaneous intra-population activity in developing
      networks. In this paper, we investigated the neuronal network activity and its
      complexity by means of self-similarity during neuronal network development. We
      studied the phenomena using computational neuronal network models and actual in
      vitro microelectrode array data measured from a developing neuronal network of
      dissociated mouse cortical neurons. To achieve this, we assessed the spiking and
      bursting characteristics of the networks, and computed the signal complexity with
      Sample Entropy. The results show that we can relate increasing simultaneous
      activity in a neuronal population with decreasing entropy, and track the network
      development and maturation using this. We can conclude that the complexity of
      neuronal network signals decreases during the maturation. This can emerge from
      the fact that as networks mature, they exhibit more synchronous activity, thus
      decreasing the complexity of its signaling. However, increasing the number of
      interacting populations has lesser effect on the signal complexity. The entropy
      based measure provides a tool to assess the complexity of the neuronal network
      activity, and can be useful in the assessment of developing networks or the
      effects of drugs and toxins on their functioning.

PMID- 29060612
TI  - Nonmotor regions encode path-related information during movements.
AB  - Sensorimotor control and the involvement of motor brain regions has been
      extensively studied, but the role nonmotor brain regions play during movements
      has been overlooked. This is particularly due to the difficulty of recording from
      multiple regions in the brain during motor control. In this study, we utilize
      stereoelectroencephalography (SEEG) recording techniques to explore the role
      nonmotor brain areas have on the way we move. Nine humans were implanted with
      SEEG depth electrodes for clinical purposes, which rendered access to local field
      potential (LFP) activity in deep and peripheral nonmotor structures. Participants
      performed fast and slow arm reaching movements using a robotic manipulandum. In
      this study, we explored whether neural activity in a given nonmotor brain
      structure correlated to movement path metrics including: path length, path
      deviation, and path speed. Statistical analysis revealed correlations between
      averaged neural activity in middle temporal gyrus, supramarginal gyrus, and
      fusiform gyrus and our path metrics both within and across the subjects.
      Furthermore, we split trials across subjects into two groups: one group consisted
      of trials with high values of each path metric and the other with low values. We
      then found significant differences in LFP power in specific frequency bands (e.g.
      beta) during movement between each group. These results suggest that nonmotor
      regions may dynamically encode path-related information during movement.

PMID- 29060613
TI  - Importance of vesicle release stochasticity in neuro-spike communication.
AB  - Aim of this paper is proposing a stochastic model for vesicle release process, a
      part of neuro-spike communication. Hence, we study biological events occurring in
      this process and use microphysiological simulations to observe functionality of
      these events. Since the most important source of variability in vesicle release
      probability is opening of voltage dependent calcium channels (VDCCs) followed by
      influx of calcium ions through these channels, we propose a stochastic model for
      this event, while using a deterministic model for other variability sources. To
      capture the stochasticity of calcium influx to pre-synaptic neuron in our model,
      we study its statistics and find that it can be modeled by a distribution defined
      based on Normal and Logistic distributions.

PMID- 29060614
TI  - Music-evoked emotion classification using EEG correlation-based information.
AB  - The relation between music and emotions has been investigated for decades. Most
      of the studies focused on short clips and were designed with specific tasks. This
      paper investigated the emotional states from electroencephalogram (EEG)
      activities during music appreciation. An emotion evoked experiment paradigm was
      designed during music appreciation. The EEG signals were recorded in 15 healthy
      adults during the entire process of music listening. The band power change (BPC)
      and higher order crossing (HOC) features were extracted from the EEG signals. A
      correlation-based feature analysis approach was proposed to find the most
      relevant features in time, frequency and channel space domains. From the results,
      this method achieved the average accuracy of 67.2% for the classification of high
      and low valence in the combination of BPC and HOC features. A deeper
      understanding of the brain emotional patterns could be helpful in building an
      intelligent and friendly affective application.

PMID- 29060616
TI  - A separated feature learning based DBN structure for classification of SSMVEP
      signals.
AB  - Signal processing is one of the key points in brain computer interface (BCI)
      application. The common methods in BCI signal classification include canonical
      correlation analysis (CCA), support vector machine (SVM) and so on. However,
      because BCI signals are very complex and valid signals often come with confounded
      background noise, many current classification methods would lose meaningful
      information embedded in human EEGs. Otherwise, due to the huge inter-subject
      variability with respect to characteristics and patterns of BCI signals, there
      often exists large difference of classification accuracy among different
      subjects. Since BCI signals have high dimensionality and multi-channel
      properties, this paper proposes a novel structure of deep belief neural (DBN)
      network stacked by restricted boltsman machine (RBM) to extract efficient
      features from steady-state motion visual evoked potential signals and implement
      further classification. Here DBN extracts local feature from BCI data of each
      channel separately and fuses the local features, and then input the fused
      features to the output classifier which is consist of softmax units. Results
      proved that the proposed algorithm could achieve higher accuracy and lower inter
      subject variability in short response time when compared to conventional CCA
      method.

PMID- 29060615
TI  - Effects of the temporal pattern of subthalamic deep brain stimulation on the
      neuronal complexity in the globus pallidus.
AB  - Deep brain stimulation (DBS) is a surgical treatment for Parkinson's disease (PD)
      but, despite clinical efficacy, the mechanisms of DBS still require
      investigation. Recent evidence suggests that the temporal pattern of the
      electrical pulses may be critical to the therapeutic merit of DBS and carefully
      designed, non-regular patterns could ameliorate some of the motor symptoms in PD.
      It is unclear, though, how different stimulation patterns affect the neural
      activity in the basal ganglia and whether this is related to the pathophysiology
      of PD. In this study, a non-human primate was treated with DBS of the subthalamic
      nucleus while single-unit recordings were collected in the animal's globus
      pallidus internus (GPi). Three stimulation patterns were applied (one regular,
      two non-regular) and the stimulation effects on the GPi spike trains were
      assessed via point process modeling. On a preliminary set of 23 GPi neurons, we
      show that regular DBS maximized the neuronal complexity, which is a measure of
      the amount of information that a single neuron can encode, and significantly
      increased the dependency of the neurons' spike trains on the background ensemble
      activity through an articulated balance of excitation and inhibition. Overall,
      regular DBS caused the largest modulation in the neurons' spiking pattern and the
      largest increment in encoding capabilities. Both results may be relevant to the
      mechanisms of therapeutic DBS.

PMID- 29060617
TI  - The obesity paradox in ICU patients.
AB  - Excessive weight is connected with an increased risk of certain life-threatening
      diseases. However, some evidence shows that among patients with chronic diseases
      such as heart failure (HF) chronic kidney disease (CKD) and COPD, increased
      weight is paradoxically associated with a decreased risk of mortality. This
      counterintuitive phenomenon is referred to as the obesity paradox. The obesity
      paradox has been mostly observed among certain cohorts of patients with HF, but
      not specific to patients in the Intensive Care Unit (ICU) setting. This paper
      studies the relationship between obesity and mortality of ICU patients with and
      without HF and presents evidence supporting the existence of this paradox. The
      results provide helpful insights for developing more patient-centric care in
      ICUs. Additionally, we use both the MIMIC-II and (recently available) MIMIC-III
      databases, for which few comparative studies exist to date. We demonstrate an
      aspect of consistency between the databases, providing a significant step towards
      validating the use of the newly announced MIMIC-III in broader studies.

PMID- 29060618
TI  - Automated embolic signal detection using Deep Convolutional Neural Network.
AB  - This work investigated the potential of Deep Neural Network in detection of
      cerebral embolic signal (ES) from transcranial Doppler ultrasound (TCD). The
      resulting system is aimed to couple with TCD devices in diagnosing a risk of
      stroke in real-time with high accuracy. The Adaptive Gain Control (AGC) approach
      developed in our previous study is employed to capture suspected ESs in real
      time. By using spectrograms of the same TCD signal dataset as that of our
      previous work as inputs and the same experimental setup, Deep Convolutional
      Neural Network (CNN), which can learn features while training, was investigated
      for its ability to bypass the traditional handcrafted feature extraction and
      selection process. Extracted feature vectors from the suspected ESs are later
      determined whether they are of an ES, artifact (AF) or normal (NR) interval. The
      effectiveness of the developed system was evaluated over 19 subjects going under
      procedures generating emboli. The CNN-based system could achieve in average of
      83.0% sensitivity, 80.1% specificity, and 81.4% accuracy, with considerably much
      less time consumption in development. The certainly growing set of training
      samples and computational resources will contribute to high performance. Besides
      having potential use in various clinical ES monitoring settings, continuation of
      this promising study will benefit developments of wearable applications by
      leveraging learnable features to serve demographic differentials.

PMID- 29060620
TI  - DeepDeath: Learning to predict the underlying cause of death with Big Data.
AB  - Multiple cause-of-death data provides a valuable source of information that can
      be used to enhance health standards by predicting health related trajectories in
      societies with large populations. These data are often available in large
      quantities across U.S. states and require Big Data techniques to uncover complex
      hidden patterns. We design two different classes of models suitable for large
      scale analysis of mortality data, a Hadoop-based ensemble of random forests
      trained over N-grams, and the DeepDeath, a deep classifier based on the recurrent
      neural network (RNN). We apply both classes to the mortality data provided by the
      National Center for Health Statistics and show that while both perform
      significantly better than the random classifier, the deep model that utilizes
      long short-term memory networks (LSTMs), surpasses the N-gram based models and is
      capable of learning the temporal aspect of the data without a need for building
      ad-hoc, expert-driven features.

PMID- 29060619
TI  - A CHF detection method based on deep learning with RR intervals.
AB  - There are extensive studies investigating congestive heart failure (CHF)
      detection based on heart rate variability. Although a high level of accuracy has
      been achieved, its robustness under different conditions is not guaranteed. To
      improve the robustness, we applied sparse auto-encoder-based deep learning
      algorithm in CHF detection with RR intervals. A total data size of 30,592 (5-min
      RR interval) was obtained from 72 healthy persons and 44 CHF patients. The deep
      learning algorithm first extracts unsupervised features using a sparse auto
      encoder from raw RR intervals, then constructs a deep neural network model with
      various hidden nodes combinations. Results showed that the model achieved 72.41%
      accuracy. This demonstrated that RR intervals have potential in CHF detection but
      cannot fully reflect dynamic change in 24-h.

PMID- 29060621
TI  - Automated vision-based analysis of levodopa-induced dyskinesia with deep
      learning.
AB  - Levodopa is the gold standard therapy for Parkinson's disease (PD), but its
      prolonged usage leads to additional motor complications, namely levodopa-induced
      dyskinesia (LID). To assess LID and adjust drug regimens for optimal relief,
      patients attend regular clinic visits. However, the intermittent nature of these
      visits can fail to capture important changes in a person's condition. With the
      recent emergence of deep learning achieving impressive results in a wide array of
      fields including computer vision, there is an opportunity for video analysis to
      be used for automated assessment of LID. Deep learning for pose estimation was
      studied as a viable means of extracting body movements from PD assessment videos.
      Movement features were computed from joint trajectories. Results show that
      features derived from vision-based analysis have moderate to good correlation
      with clinician ratings of dyskinesia severity. This study presents the first
      application of deep learning to video analysis in PD, and demonstrates promise
      for future development of a non-contact system for objective PD assessment.

PMID- 29060622
TI  - Pilot study on vascular intervention training based on blood flow effected
      guidewire simulation.
AB  - A decent guidewire behavior simulation is vital to the virtual vascular
      intervention training. The influence of blood flow has rarely been taken into
      consideration in former works of guidewire simulation. This paper addresses the
      problem by integrating blood flow analysis and proposes a novel guidewire
      simulation model.The blood flow distribution inside arterial vasculature is
      computed by separating the vascular model into discrete cylindrical vessels and
      modeling the flow in each vessel with the Poiseuille Law. The blood flow
      computation is then integrated into a Kirchhoff rods model. The simulation could
      be run in real time with hardware acceleration at least 30 fps. To validate the
      result, an experiment environment with a 3D printed vascular phantom and an
      electromagnetic tracking(EMT) system was set up with clinical-used guidewire
      sensors applied in phantom to trace its motion as the standard for comparison.
      Experiment results reveal that the shown blood flow effected model presents
      better physical credibility with a lower and more stable root-mean-square(RMS) at
      2.14mm +/- 1.24mm, better than the Kirchhoff model of 4.81mm+/-3.80mm.

PMID- 29060623
TI  - Applying computer simulation to the design of flow-diversion treatment for
      intracranial aneurysms.
AB  - Although flow-diversion (FD) treatment has been proven to be able to induce
      intracranial aneurysm (IA) occlusion, clinical follow-ups reported that a number
      of patients may still suffer from delayed IA rupture or incomplete aneurysm
      occlusion post-treatment. Complete aneurysm occlusion is believed to be
      associated with favourable haemodynamic alteration post-treatment, which may be
      greatly affected by the selection of device size and quantity, as well as the FD
      deployment procedure. However, clinicians have to choose and deploy the FD
      relying on their experience, since no post-stenting haemodynamic information is
      generally available to them prior to a specific treatment. In this study, using a
      virtual FD deployment technique and computational fluid dynamics method, we
      demonstrate and compare the haemodynamic changes after virtual FD treatments
      using a variety of prospective treating strategies.

PMID- 29060624
TI  - Sensitivity study on modelling a flow-diverting stent as a porous medium using
      computational fluid dynamics.
AB  - The flow-diverting (FD) stent has become a commonly used endovascular device to
      treat cerebral aneurysms. This discourages blood from entering the aneurysm,
      thereby reducing the likelihood of aneurysm rupture. Using computational fluid
      dynamics (CFD) to simulate the aneurysmal haemodynamics after FD treatment could
      help clinicians predict the stent effectiveness prior to the real procedure in
      the patient. As an alternative to modelling the stent as a fine wire mesh,
      modelling the FD stent as a porous medium was established to save computational
      time, and has also been proved capable of predicting the same haemodynamics as
      obtained using the real FD stent geometry. The flow resistance effect of a porous
      medium stent may differ with respect to its morphology or permeability; however,
      the flow resistance effect after adjusting these parameters had not been
      clarified. In this study, we analysed the haemodynamic changes caused by
      alterations of porous-medium thickness and permeability, thereby providing future
      porous-medium stent simulations with important information on the respective
      parametric sensitivities. We found significant sensitivity to permeability.
      Results were insensitive to thickness when permeability was adjusted beforehand
      to compensate. We also compared our results with observations from an in-vitro
      model, and found good agreement. This supports adoption of porous-medium models
      in future work.

PMID- 29060625
TI  - An HMM-based recognition framework for endovascular manipulations.
AB  - Robotic surgical systems are becoming increasingly popular for the treatment of
      cardiovascular diseases. However, most of them have been designed without
      considering techniques and skills of natural surgical manipulations, which are
      key factors to clinical success of percutaneous coronary intervention. This paper
      proposes an HMM-based framework to recognize six typical endovascular
      manipulations for surgical skill analysis. A simulative surgical platform is
      built for endovascular manipulations assessed by five subjects (1 expert and 4
      novices). The performances of the proposed framework are evaluated by three
      experimental schemes with the optimal model parameters. The results show that
      endovascular manipulations are recognized with high accuracy and reliable
      performance. Furthermore, the acceptable results can also be applied to the
      design of next generation vascular interventional robots.

PMID- 29060626
TI  - Effect of catheter positions on hemodynamics and coil formation after coil
      embolization.
AB  - Coil embolization using a micro catheter and coils is one of the most popular
      surgical methods used for treating intracranial aneurysms. Surgeons need to
      better understand the effects of changing catheter position because this is under
      their control during operations. In this study, we simulate coil embolization for
      a basic bifurcation-type aneurysm using finite element method and computational
      fluid dynamics. We evaluated the reduction in velocity after embolization and the
      distance of the embolized coil's center of gravity from the center of the
      aneurysm (rCG) while changing the catheter tip position. The results show there
      is a high correlation between velocity reduction and neck volume embolization
      ratio (NVER) with a correlation coefficient of 0.955, and between the catheter
      tip position and rCG with a correlation coefficient of 0.866. These results
      indicate the NVER is also important for effective velocity reduction in both
      bifurcation-type and sidewall-type aneurysms. In addition, it is useful to set
      the catheter tip at the bottom of the aneurysms to deploy the first coil as a
      framing coil.

PMID- 29060627
TI  - Effects of septum and pericardium on heart-lung interactions in a cardiopulmonary
      simulation model.
AB  - Mechanical heart-lung interactions are often overlooked in clinical settings.
      However, their impact on cardiac function can be quite significant. Mechanistic
      physiology-based models can provide invaluable insights into such
      cardiorespiratory interactions, which occur not only under external mechanical
      ventilatory support but in normal physiology as well. In this work, we focus on
      the cardiac component of a previously developed mathematical model of the human
      cardiopulmonary system, aiming to improve the model's response to the
      intrathoracic pressure variations that are associated with the respiratory cycle.
      Interventricular septum and pericardial membrane are integrated into the existing
      model. Their effect on the overall cardiac response is explained by means of
      comparison against simulation results from the original model as well as
      experimental data from literature.

PMID- 29060628
TI  - Volumetric analysis of respiratory gated whole lung and liver CT data with motion
      constrained graph cuts segmentation.
AB  - The conventional graph cuts technique has been widely used for image segmentation
      due to its ability to find the global minimum and its ease of implementation.
      However, it is an intensity-based technique and as a result is limited to
      segmentation applications where there is significant contrast between the object
      and the background. We modified the conventional graph cuts method by adding
      shape prior and motion information. Active shape models (ASM) with signed
      distance functions were used to capture the shape prior information, preventing
      unwanted surrounding tissue from becoming part of the segmented object. The
      optical flow method was used to estimate the local motion and to extend 3D
      segmentation to 4D by warping a prior shape model through time. The method has
      been applied to segmentation of whole lung boundary and whole liver boundary from
      respiratory gated CT data. 4D lung boundary segmentation in five patients, and 4D
      liver boundary segmentation in five patients were performed and in each case,
      results were compared with the results from expert-delineated ground truth. 4D
      segmentation for five phases of CT data took approximately ten minutes on a PC
      workstation with AMD Phenom II and 32GB of memory. An important by-product is
      quantitative whole organ volumes from respiratory gated CT from end-inspiration
      to end-expiration which can be determined with high accuracy.

PMID- 29060629
TI  - Development of a radiobiological evaluation tool to assess the expected clinical
      impacts of contouring accuracy between manual and semi-automated segmentation
      algorithms.
AB  - RADEval is a tool developed to assess the expected clinical impact of contouring
      accuracy when comparing manual contouring and semi-automated segmentation. The
      RADEval tool, designed to process large scale datasets, imported a total of 2,760
      segmentation datasets, along with a Simultaneous Truth and Performance Level
      Estimation (STAPLE) to act as ground truth tumor segmentations. Virtual dose-maps
      were created within RADEval and two different tumor control probability (TCP)
      values using a Logistic and a Poisson TCP models were calculated in RADEval using
      each STAPLE and each dose-map. RADEval also virtually generated a ring of normal
      tissue. To evaluate clinical impact, two different uncomplicated TCP (UTCP)
      values were calculated in RADEval by using two TCP-NTCP correlation parameters
      (delta = 0 and 1). NTCP values showed that semi-automatic segmentation resulted
      in lower NTCP with an average 1.5 - 1.6 % regardless of STAPLE design. This was
      true even though each normal tissue was created from each STAPLE (p <; 0.00001).
      TCP and UTCP presented no statistically significant differences (p >= 0.1884).
      The intra-operator standard deviations (SDs) for TCP, NTCP and UTCP were
      significantly lower for the semi-automatic segmentation method regardless of
      STAPLE design (p <; 0.0331). Both intra-and inter-operator SDs of TCP, NTCP and
      UTCP were significantly lower for semi-automatic segmentation for the STAPLE 1
      design (p <;0.0331). RADEval was able to efficiently process 4,920 datasets of
      two STAPLE designs and successfully assess the expected clinical impact of
      contouring accuracy.

PMID- 29060630
TI  - Angled tooth segmentation from computerized tomography images.
AB  - Tooth contour segmentation from dental computerized tomography (CT) images is one
      of the fundamental steps in reconstructing the three-dimensional models of teeth.
      However, existing methods depend on the tooth shape similarity between adjacent
      slices, and have difficulty to segment these angled teeth whose contour shapes
      from adjacent slices may differ a lot. This study proposes a new method for
      contour segmentation of angled teeth from CT images. The volume of interest (VOI)
      of target tooth and corresponding tooth axis are first extracted from volumetric
      CT images. Local images within the VOI of target tooth are then rotated such that
      the tooth axis in the rotated images is perpendicular to the transverse section.
      Tooth contours are finally segmented from the rotated images using a hybrid level
      set model slice-by-slice. Experimental results verified that the proposed method
      was effective to segment contours of angled teeth from CT images.

PMID- 29060631
TI  - Automatic measurement of fetal Nuchal translucency from three-dimensional
      ultrasound data.
AB  - The Nuchal translucency (NT), which is the collection of fluid at the back of the
      fetal neck, is related to chromosomal defects and early cardiac failure in first
      trimester of pregnancy. In clinic, the thickness of NT is used as an important
      marker in prenatal screening, and is manually measured by sonographers in the mid
      sagittal plane. In this paper, an automatic method based on dynamic programming
      is proposed to detect the thickness and area of NT in the mid-sagittal plane.
      Furthermore, the volume of NT in the whole three-dimensional ultrasound data is
      also measured. A novel cost function for dynamic programming is proposed and
      results in higher accuracy of NT border detection. As the nuchal translucency is
      the collection fluid part, higher dimensional markers of NT possess more
      potential to represent the amount of the fluid.

PMID- 29060632
TI  - Brain segmentation in MR images using a texture-based classifier associated with
      mathematical morphology.
AB  - Skull stripping, which refers to the segmentation of brain tissue from non-brain
      tissue, has been challenging due to the ramification of the human brain
      structures and volatile parameters in the magnetic resonance imaging (MRI)
      procedures. It has been one of the most critical preprocessing steps in medical
      image analysis. We propose a hybrid skull stripping algorithm that is based on
      texture feature analysis, fuzzy possibilistic c-means (FPCM), and morphological
      operations. The input MR image is first processed to obtain two texture feature
      maps, to which the FPCM is applied for acquiring brain and non-brain masks. A
      number of morphological operations are subsequently performed to extract the
      brain. Our algorithm has been compared with two famous methods and evaluated on
      the internet brain segmentation repository (IBSR) datasets. Preliminary
      experimental results suggested that this new framework achieved high accuracy and
      outperformed the compared methods. We believe that the proposed scheme is of
      effectively potential in a wide variety of brain MR image segmentation
      applications.

PMID- 29060633
TI  - Segmentation of hyper-acute cerebral infarct based on random forest and sparse
      coding from diffusion weighted imaging.
AB  - Irreversible infarcts are critical for the assessment of potential risk and
      benefit pertaining to thrombolysis in hyper-acute ischemic stroke. It is a
      challenging work to segment infarct at hyper-acute stage due to the substantial
      variability. A general abnormal tissue segmentation method is proposed and
      applied to segment hyper-acute ischemic infarct in this paper. Multiple features
      are designed to train a random forest classifier for voxel classification. Sparse
      coding based bag-of-features is adopted to train a region classifier for infarct
      region recognition. The proposed method has been validated on 98 consecutive
      patients recruited within 6 hours from onset and achieved a higher Dice
      coefficient 0.774+/-0.117 than the other two existing methods (0.755+/-0.118;
      0.597+/-0.204). It could provide a potential tool to quantify infarcts from
      diffusion weighted imaging at hyper-acute stage with accuracy to assist the
      decision making especially for thrombolytic therapy.

PMID- 29060634
TI  - Development of a gesture and voice controlled system for burn injury prevention
      in individuals with disabilities.
AB  - Burn injury is a major public health issue in developing countries, with most
      injuries being largely associated with the use of kitchen stoves. This study
      details the development of a cost-effective gesture and voice recognition
      controlled (GVC) system to be used by individuals with disabilities to reduce the
      likelihood of burn injury and improve their quality of life. The device replaces
      conventional dial controls with voice and hand gesture recognition sensors and
      software which are designed to be easily implemented into a household kitchen.
      Preliminary evaluation of the GVC system's performance in gesture and voice
      recognition, gas leak detection and ignition control tests were conducted using a
      Bunsen burner as a stove top surrogate. The voice and gesture recognition tests
      yielded sensitivities of 88% and 100%, respectively. These results suggest that
      the GVC system may be a promising solution for burn injury prevention pending
      further work to improve its reliability and robustness.

PMID- 29060635
TI  - A novel mainstream capnometer system for endoscopy delivering oxygen.
AB  - Capnometry is a method to measure carbon dioxide (CO2) in exhaled gas and it has
      been used in patients to monitor their respiratory status. Monitoring of exhaled
      CO2 during endoscopic procedures has been shown to be effective in detecting drug
      induced respiratory depression. Oxygen (O2) supplementation is given to patients
      to abolish hypoxia during endoscopy. However, oxygen administration can interfere
      with CO2 measurement owing to oxygen flow. Therefore, we developed cap-ONE
      Biteblock for patients undergoing endoscopy with oxygen supply to measure CO2
      accurately. In this study we evaluated the basic performance of cap-ONE
      Biteblock. The cap-ONE Biteblock system could accurately measure CO2 and
      efficiently supply O2 comparing to conventional devices via a bench study.

PMID- 29060636
TI  - A novel smartphone camera-LED Communication for clinical signal transmission in
      mHealth-rehabilitation system.
AB  - In this paper, an implementation of mobile-Visible Light Communication (mVLC)
      technology for clinical data transmission in home-based mobile-health (mHealth)
      rehabilitation system is introduced. Mobile remote rehabilitation program is the
      solutions for improving the quality of care of the clinicians to the patients
      with chronic condition and disabilities. Typically, the program inquires routine
      exercise which obligate patients to wear wearable electronic sensors for hours in
      a specific range of time. Thus it motivate us to develop a novel harmless
      biomedical communicating system since most of the device's protocol was based on
      RF communication technology which risky for a human body in term of long term
      usage due to RF exposure and electromagnetic interference (EMI). The proposed
      system are designed to utilize a visible light as a medium for hazardless
      communication between wearable sensors and a mobile interface device
      (smartphone). Multiple clinical data such as photoplethysmogram (PPG),
      electrocardiogram (ECG), and respiration signal are transmitted through LED and
      received by a smartphone camera. Furthermore, a smartphone also used for local
      interface and data analyzer henceforth sent the data to the cloud for further
      clinician's supervision.

PMID- 29060637
TI  - Profiling a multiplex short tandem repeat loci from human urine with use of low
      cost on-site technology for verification of sample authenticity.
AB  - This work focuses on the development of a sophisticated technique via STR typing
      to unequivocally verify the authenticity of urine samples before sent to
      laboratories. STR profiling was conducted with the CSF1PO, TPOX, TH01 Multiplex
      System coupled with a smartphone-based detection method. The promising capability
      of the method to identify distinct STR profiles from urine of different persons
      opens the possibility to conduct sample authenticity tests. On-site STR profiling
      could be realized with a self-contained autonomous device with an integrated PCR
      microchip shown hereby.

PMID- 29060638
TI  - Fall detection using smart floor sensor and supervised learning.
AB  - Falls are a major risk for elderly people's health and independence. Fast and
      reliable fall detection systems can improve chances of surviving the accident and
      coping with its physical and psychological consequences. Recent research has come
      up with various solutions, all suffering from significant drawbacks, one of them
      being the intrusiveness into patient's life. This paper proposes a novel fall
      detection monitoring system based on a sensitive floor sensor made out of a
      piezoelectric material and a machine learning approach. The detection is done by
      a combination between a supervised Random Forest and an aggregation of its output
      over time. The database was made using acquisitions from 28 volunteers simulating
      falls and other behaviours. Unlike existent fall detection systems, our solution
      offers the advantages of having a passive sensor (no power supply is needed) and
      being completely unobtrusive since the sensor comes with the floor. Results are
      compared with state-of-the-art classification algorithms. On our database, good
      performance of fall detection was obtained with a True Positive Rate of 94.4% and
      a False Positive Rate of 2.4%.

PMID- 29060639
TI  - Respiration and heartbeat monitoring using a distributed pulsed MIMO radar.
AB  - This paper addresses non-contact monitoring of physiological signals induced by
      respiration and heartbeat. To detect the tiny physiological movements of the
      chest or other parts of the torso, a Mulitple-Input Multiple-Output (MIMO) radar
      is used. The spatially distributed transmitters and receivers are able to detect
      the chest surface movements of one or multiple persons in a room. Due to several
      bistatic measurements at the same time a robust detection and measuring of the
      breathing and heartbeat rate is possible. Using an appropriate geometrical
      configuration of the sensors even a localization of the person is feasible.

PMID- 29060640
TI  - Simulations of high-density surface electromyograms in dynamic muscle
      contractions.
AB  - We describe the extension of pre-existing cylindrical volume conductor model to
      synthetic high-density surface electromyograms (hdEMG), simulated during dynamic
      contractions of fusiform skeletal muscles. Its modular structure comprises two
      main parts. First, dynamic changes of motor unit action potentials (MUAPs) during
      36 discrete steps of muscle shortening are simulated. Second, the increase in
      depth of simulated motor units (MUs) due to shortening and thickening of muscle
      fibers is simulated. MU firing patterns are generated with the model proposed by
      Fuglevand et al. and convolved with simulated MUAPs. In this way, the hdEMG
      simulator can be used to generate dynamic hdEMG of arbitrary muscle shortening,
      thickening and excitation profiles. In order to demonstrate the value of the
      aforementioned simulator we independently analyze the impact of muscle shortening
      and muscle thickening on MU identification by Convolution Kernel Compensation
      (CKC) technique.

PMID- 29060641
TI  - Performance evaluation of Noise-Assisted Multivariate Empirical Mode
      Decomposition and its application to multichannel EMG signals.
AB  - The use of the Empirical Mode Decomposition (EMD) for nonlinear signal processing
      has been popularized in the recent years. However, its utility for the processing
      of multichannel Electromyography (EMG) signals is still limited. This paper
      investigates the decomposition performance of multichannel EMGs by using the EMD
      based approaches, Ensemble EMD (EEMD), Multivariate EMD (MEMD), and Noise
      Assisted MEMD (NA-MEMD). In the experiment, 11 male subjects undergo three
      exercise programs, leg extension from a sitting position, flexion of the leg up,
      and gait, while electrodes are placed on the muscle groups, biceps femoris,
      vastus medialis, rectus femoris, and semitendinosus. The outcomes are then
      quantitatively estimated on the basis of three criterions, the number of
      Intrinsic Mode Functions (IMFs), mode-alignment and mode-mixing. Results show
      both MEMD and NA-MEMD can guarantee equal numbers of IMFs, whereas for mode
      alignment and mode-mixing, NA-MEMD is optimal compared with MEMD and EEMD, and
      MEMD is merely better than EEMD. This finding implies that NA-MEMD is effective
      for simultaneously analyzing IMFs based frequency bands. It has a vital clinical
      implication in exploring the neuromuscular patterns that enable the multiple
      muscle groups to coordinate while performing functional activities of daily
      living.

PMID- 29060642
TI  - Measuring the interactions between different locations in a muscle to monitor
      localized muscle fatigue.
AB  - In this study we investigated a technique for estimating the progression of
      localized muscle fatigue. This technique measures the dependence between motor
      units using high density surface electromyogram (HD-sEMG) and is based on the
      Normalized Mutual Information (NMI) measure. The NMI between every pair
      combination of the electrode array is computed to measure the interactions
      between electrodes. Participants in the experiment had an array of 64 electrodes
      (16 by 4) placed over the TA of their dominate leg such that the columns of the
      array ran parallel with the muscle fibers. The HD-sEMG was recorded whilst the
      participants maintained an isometric dorsiflexion with their dominate foot until
      task failure at 40% and 80% of their maximum voluntary contraction (MVC). The
      interactions between different locations over the muscle were computed using the
      recorded HD-sEMG signals. The results show that the average interactions between
      various locations over the TA significantly increased during fatigue at both
      levels of contraction. This can be attributed to the dependence in the motor
      units.

PMID- 29060643
TI  - Analysis of one repetition during biceps curl exercise among age-matched adult
      volunteers using endurance, curl speed and surface electromyography signals.
AB  - Exercises under isometric and dynamic contractions are influenced by the rate
      coding and recruitment strategies. The study of muscle strength under dynamic
      contraction is normally performed using one-repetition maximum (1-RM) method.
      There are several variants of deriving one repetition method using number of
      repetitions and load that are useful in physical fitness and clinical
      rehabilitation program. However, the factors of dynamic contractions such as
      endurance time, speed of muscle contractions and muscle activity are not
      considered in 1-RM methods. The muscular activities are analyzed using surface
      electromyography (sEMG) signals. Limited work has been reported on the
      relationship between the 1-RM method and factors such as endurance time, speed of
      contraction and sEMG activity. In this work, a modified 1-RM method is proposed,
      namely, N-RM, using load, number of repetitions, endurance time, speed of
      contraction and normalized sEMG activity. For this purpose, sEMG signals are
      recorded from 58 healthy subjects under standard dynamic contraction protocol
      involving curl exercise. Conventional 1-RM is computed by using Epley's method
      and compared with proposed method using correlation analysis. The results show
      that 1-RM increases linearly with number of curls (r=1) but has a poor
      correlation coefficient with sEMG (r=0.01) and endurance time (r =0.4). The curl
      speed for lower 1-RM and higher 1-RM did not show any statistical difference (p
      =0.2). The proposed N-RM is observed to have good correlation with endurance time
      (r=0.734), curl speed (r=0.893) and sEMG activity (r=0.8851). These results
      demonstrate that the proposed N-RM is highly correlated to factors influencing
      the dynamic contractions. This method can be further extended to assess muscles
      under various clinical disorders and sports training.

PMID- 29060644
TI  - Antagonist thigh-muscle activity in 6-to-8-year-old children assessed by surface
      EMG during walking.
AB  - Analysis of muscle co-contractions seems to be relevant in the characterization
      of children pathologies such as spastic cerebral palsy. The aim of the study was
      the quantification of thigh-muscle co-contractions during walking in healthy
      children. To this aim, the Statistical Gait Analysis, a recent methodology
      providing a statistical characterization of gait, was performed on surface EMG
      signals from Vastus Medialis (VM) and Lateral Hamstrings (LH) in 30 healthy 6-to
      8-year-old children. Muscular co-contraction was assessed as the overlapping
      period between activation intervals of agonist and antagonist muscles. As in
      adults, VM activity occurring from terminal swing to the following loading
      response superimposed LH activity in the same percentage of the gait cycle. This
      co-contraction occurred in order to control knee joint stability during weight
      acceptance. It was acknowledged in the totality (100 %) of the considered
      strides. Concomitant activity of VM and LH was detected also in the second half
      of stance phase in 17.1 +/- 4.8 % of the considered strides. Working VM and LH on
      different joints, this concomitant activity of antagonist muscles should not be
      considered as an actual co-contraction. Present findings provide new information
      on the variability of the reciprocal role of VM and LH during child walking,
      useful for comparison between normal and pathological walking in the clinical
      context and for designing future studies on maturation of gait.

PMID- 29060645
TI  - Characterization of doctor-patient communication using heartbeat nonlinear
      dynamics: A preliminary study using Lagged Poincare Plots.
AB  - Emphatic doctor-patient communication has been associated with an improved psycho
      physiological well-being involving cardiovascular and neuroendocrine responses.
      Nevertheless, a comprehensive assessment of heartbeat linear and
      nonlinear/complex dynamics throughout the communication of a life-threatening
      disease has not been performed yet. To this extent, we here study heart rate
      variability (HRV) series gathered from 17 subjects while watching a video where
      an oncologist discloses the diagnosis of a cancer metastasis to a patient.
      Further 17 subjects watched the same video including additional affective
      emphatic contents. For the assessment of the two groups, linear heartbeat
      dynamics was quantified through measures defined in the time and frequency
      domains, whereas nonlinear/complex dynamics referred to measures of entropy, and
      combined Lagged Poincare Plots (LPP) and symbolic analyses. Considering
      differences between the beginning and the end of the video, results from non
      parametric statistical tests demonstrated that the group watching emphatic
      contents showed HRV changes in the LF/HF ratio exclusively. Conversely, the group
      watching the purely informative video showed changes in vagal activity (i.e., HF
      power), LF/HF ratio, as well as LPP measures. Additionally, a Support Vector
      Machine algorithm including HRV nonlinear/complex information was able to
      automatically discern between groups with an accuracy of 76.47%. We therefore
      propose the use of heartbeat nonlinear/complex dynamics to objectively assess the
      empathy level of healthy women.

PMID- 29060646
TI  - Multifractal multiscale dfa of cardiovascular time series: Differences in complex
      dynamics of systolic blood pressure, diastolic blood pressure and heart rate.
AB  - The heart-rate fractal dynamics can be assessed by Detrended Fluctuation Analysis
      (DFA), originally proposed for estimating a short-term coefficient, alpha1 (for
      scales n<=12 beats), and a long-term coefficient alpha2 (for longer scales).
      Successively, DFA was extended to provide a multiscale alpha, i.e. a continuous
      function of n, alpha(n); or a multifractal alpha, i.e. a function of the order q
      of the fluctuations moment, alpha(q). Very recently, a multifractal-multiscale
      DFA was proposed for evaluating multifractality at different scales separately.
      Aim of this work is to describe the multifractal multiscale dynamics of three
      cardiovascular signals often recorded beat by beat in physiological and clinical
      settings: systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse
      interval (PI, inverse of the heart rate). We recorded SBP, DBP and PI for at
      least 90' in 65 healthy volunteers at rest, and adapted the previously proposed
      multifractal multiscale DFA to estimate alpha as function of the temporal scale,
      tau, between 15 and 450 s, and of the order q, between -5 and 5. We report, for
      the first time: 1) substantial differences among alpha(q,tau) surfaces of PI, SBP
      and DBP; 2) a strong dependency of the degree of multifractality on the temporal
      scale.

PMID- 29060647
TI  - Cardiovascular and respiratory variability during orthostatic and mental stress:
      A comparison of entropy estimators.
AB  - The aim of this study is to characterize cardiovascular and respiratory signals
      during orthostatic and mental stress as reflected in indices of entropy and
      complexity, providing a comparison between the performance of different
      estimators. To this end, the heart rate variability, systolic blood pressure,
      diastolic blood pressure and respiration time series were extracted from the
      recordings of 61 healthy volunteers undergoing a protocol consisting of supine
      rest, head-up tilt test and mental arithmetic task. The analysis was performed in
      the information domain using measures of entropy and conditional entropy,
      estimated through model-based (linear) and model-free (binning, nearest neighbor)
      approaches. Our results show that different types of stress elicited different
      responses in the employed indices. On one hand, entropy mainly reflected known
      changes in the variance of physiological time series. On the other hand, the
      information conveyed by conditional entropy allowed to characterize the
      complexity of the four time series during the two stress tasks: we found that
      cardiac and vascular dynamics underwent a reduction in complexity as a
      consequence of postural stress, while vascular and respiratory complexity
      increased as a result of mental stress. As for the performance of different
      estimators, we did not find substantial differences between model-based and model
      free approaches, possibly indicating that significant non-linear dynamics did not
      appear in the studied conditions.

PMID- 29060648
TI  - Secondary measures of regularity from an entropy profile in detecting Arrhythmia.
AB  - The most recently introduced concept of a 'complete entropy profile' is a non
      parametric (with regard to tolerance r) approach of entropy estimation. Given a
      signal, on generating its complete entropy profile, numerous secondary measures
      of regularity can be derived from the same. These profile based measures are seen
      to outperform the traditional ApEn statistic (evaluated at a single r) in
      estimating signal regularity. In this paper, we compare the performance of ApEn
      (evaluated at an r = 0.15 * SD of signal and an m = 2) with that of profile based
      measures such as MaxApEn, TotalApEn, AvgApEn, SDApEn, kurtApEn and skewApEn, in
      detecting 'Arrhythmic' RR interval signals from 'Normal' RR interval signals.
      Results indisputably prove the superiority of AvgApEn (AUC > 0.9 at data lengths
      N >= 200) and MaxApEn (AUC > 0.75 at all data lengths) as regularity statistics
      in detecting Arrhythmia, above all the other measures used.

PMID- 29060649
TI  - Multivariate symbolic dynamics for analysis of respiratory-cardiovascular
      interactions.
AB  - In this work, a nonlinear method to study multivariate interactions, called
      multivariate symbolic dynamics (MSD), was introduced. The usefulness of this
      technique was studied on respiratory-cardiovascular data from young women with
      vasovagal syncope (VVS) and from healthy subjects. The study included 16 female
      patients diagnosed with VVS and 24 age-matched healthy subjects (12 women). All
      subjects were enrolled in a head-up tilt (HUT) test, breathing normally,
      including 5 min of supine position and 18 to 28 min of 70 degrees  orthostatic
      phase. The MSD parameters were dynamically obtained for 5-min windows shifted by
      1 min during HUT test. In supine position there were no considerable differences.
      During orthostatic phase, parameters from MSD showed a highly significantly
      (p=0.00005) increased occurrence of impaired respiratory-cardiovascular
      interactions in female patients susceptible to vasovagal syncope. This study
      provided promising results for a new multivariate method to investigate
      respiratory-cardiovascular interactions.

PMID- 29060650
TI  - Nonlinear dynamic analysis of the cardiorespiratory system in patients undergoing
      the weaning process.
AB  - In this work, the cardiorespiratory pattern of patients undergoing extubation
      process is studied. First, the respiratory and cardiac signals were resampled,
      next the Symbolic Dynamics (SD) technique was implemented, followed of a
      dimensionality reduction applying Forward Selection (FS) and Moving Window with
      Variance Analysis (MWVA) methods. Finally, the Linear Discriminant Analysis (LDA)
      and Support Vector Machines (SVM) classifiers were used. The study analyzed 153
      patients undergoing weaning process, classified into 3 groups: Successful Group
      (SG: 94 patients), Failed Group (FG: 39 patients), and patients who had been
      successful during the extubation and had to be reintubated before 48 hours,
      Reintubated Group (RG: 21 patients). According to the results, the best
      classification present an accuracy higher than 88.98 +/- 0.013% in all proposed
      combinations.

PMID- 29060651
TI  - A cancelable biometric scheme based on multi-lead ECGs.
AB  - Biometric technologies offer great advantages over other recognition methods, but
      there are concerns that they may compromise the privacy of individuals. In this
      paper, an electrocardiogram (ECG)-based cancelable biometric scheme is proposed
      to relieve such concerns. In this scheme, distinct biometric templates for a
      given beat bundle are constructed via "subspace collapsing." To determine the
      identity of any unknown beat bundle, the multiple signal classification (MUSIC)
      algorithm, incorporating a "suppression and poll" strategy, is adopted. Unlike
      the existing cancelable biometric schemes, knowledge of the distortion transform
      is not required for recognition. Experiments with real ECGs from 285 subjects are
      presented to illustrate the efficacy of the proposed scheme. The best recognition
      rate of 97.58 % was achieved under the test condition Ntrain = 10 and Ntest = 10.

PMID- 29060652
TI  - Adaptive Fourier decomposition based R-peak detection for noisy ECG Signals.
AB  - An adaptive Fourier decomposition (AFD) based R-peak detection method is proposed
      for noisy ECG signals. Although lots of QRS detection methods have been proposed
      in literature, most detection methods require high signal quality. The proposed
      method extracts the R waves from the energy domain using the AFD and determines
      the R-peak locations based on the key decomposition parameters, achieving the
      denoising and the R-peak detection at the same time. Validated by clinical ECG
      signals in the MIT-BIH Arrhythmia Database, the proposed method shows better
      performance than the Pan-Tompkin (PT) algorithm in both situations of a native PT
      and the PT with a denoising process.

PMID- 29060653
TI  - A robust automatic mechanism for electrocardiogram interpretation in
      telehealthcare.
AB  - Telehealthcare has become increasingly popular in clinical practice as a means of
      providing ubiquitous healthcare through long-term informative interactions and
      health monitoring. We have delivered a synchronized telehealthcare program since
      2009. We have implemented a web-based clinical decision support system with a
      knowledge-based electrocardiogram (ECG) recognition mechanism as an augmentation
      service to assist medical practitioners doing decision making in clinical
      practice. To evaluate the capability and usage limits of this automatic ECG
      interpretation, the aim of this study was to validate the stability and
      robustness of proposed mechanism using stress testing through six simulation
      scenarios. According to experimental results, both of the processing items and
      processing time augmented steadily by the resource of hardware. Besides, under
      the cross-validation using 327,058 ECG signals from our telehealthcare program,
      the recognition classifiers yielded 86.8% accuracy in sinus detection and 88.4%
      accuracy in atrial fibrillation detection. In the future, this prominent
      mechanism of automatic ECG interpretation could widely offer high accessibility
      in the field of medical service. The findings of the present study also encourage
      and augment further support to implementation of screening and monitoring as part
      of telehealthcare.

PMID- 29060654
TI  - Designing ECG-based physical unclonable function for security of wearable
      devices.
AB  - As a plethora of wearable devices are being introduced, significant concerns
      exist on the privacy and security of personal data stored on these devices.
      Expanding on recent works of using electrocardiogram (ECG) as a modality for
      biometric authentication, in this work, we investigate the possibility of using
      personal ECG signals as the individually unique source for physical unclonable
      function (PUF), which eventually can be used as the key for encryption and
      decryption engines. We present new signal processing and machine learning
      algorithms that learn and extract maximally different ECG features for different
      individuals and minimally different ECG features for the same individual over
      time. Experimental results with a large 741-subject in-house ECG database show
      that the distributions of the intra-subject (same person) Hamming distance of
      extracted ECG features and the inter-subject Hamming distance have minimal
      overlap. 256-b random numbers generated from the ECG features of 648 (out of 741)
      subjects pass the NIST randomness tests.

PMID- 29060655
TI  - A body position influence on ECG derived respiration.
AB  - An influence of a human body position on ECG derived respiration (EDR) signal is
      presented in the paper. Examinations were performed during deep, suspended and
      normal breathing for eight people in four different body positions. EDR and
      thoracic impedance signals were compared using correlation and standard deviation
      coefficients. Obtained results have shown that it is possible to monitor breath
      activity of people being in different position, however a precise interpretation
      of the obtained signal is limited.

PMID- 29060656
TI  - Pattern discovery and similarity assessment for robust Heart Sound Segmentation.
AB  - Heart Sound Segmentation plays a fundamental role in pathology detection in
      Phonocardiogram (PCG) signals. This matter of study has been widely studied in
      the past decades, however the majority of algorithms' results correspond only to
      small databases, composed by only quality signals or signals specific to one
      acquisition system. In this work we proposed a robust segmentation algorithm
      integrated with clinical information, based on a pattern recognition approach for
      segmentation of the fundamental heart sounds, which is validated in several
      databases from different countries and with different acquisition
      instrumentations. The database comprises a total of 3153 recordings from 764
      patients with a variety of pathological conditions. The general results were 95%
      and 96% of sensitivity and positive predictivity, respectively. Based on the
      results the algorithm is able to perform with accuracy maintaining generalization
      capabilities.

PMID- 29060657
TI  - White matter integrity correlates with choline level in dorsal anterior cingulate
      cortex of obsessive compulsive disorder patients: A combined DTI-MRS study.
AB  - Structural and functional neuroimaging studies have indicated that the cortico
      striato -thalamo-cortical (CSTC) circuit contributes to the pathophysiology of
      obsessive compulsive disorder (OCD). As an essential component of CSTC circuit,
      the dorsal anterior cingulate cortex (dACC) plays an important role for its
      advanced function in cognition and emotion control. A comprehensive understanding
      of the dACC disruption in OCD pathological mechanism is desired. In this study,
      we performed a combined diffusion tensor imaging (DTI) and magnetic resonance
      spectroscopy (MRS) study in 15 OCD patients and 15 healthy controls to
      investigate the association between structural abnormality and metabolic
      alterations within the dACC area. We found a positive correlation between the
      dACC fractional anisotropy (FA) value and choline concentration in patients.
      Moreover, the FA was positively associated with OCD clinical symptom, especially
      the compulsive behavior, which showed the clinical relevance of dACC white matter
      integrity in OCD. To our knowledge, the present work is the first combined DTI
      MRS study of OCD. Our findings demonstrated the co-occurrence of structural and
      metabolic changes within dACC in OCD patients. It was suggested that the
      disrupted white matter integrity might be accompanied with degraded cellular
      membrane turnover.

PMID- 29060658
TI  - A 3D model-based simulation of demyelination to understand its effects on
      diffusion tensor imaging.
AB  - Demyelination is the progressive damage to the myelin sheath, a protective
      covering that surrounds a nerve's axon. Due to its high sensitivity to
      microscopic tissue changes, diffusion tensor imaging (DTI) is a powerful means of
      detecting signs of demyelination and axonal injury. In this paper, we present a
      3D virtual model capable of simulating the complex Brownian motion of water
      molecules in a bundle of myelinated axons and glial cells for the purpose of
      synthesizing DTI data, characterizing and verifying the impact of demyelination
      on DTI. Our model consists of a highly detailed and realistic 3D representation
      of biological fiber bundles, with a myelin sheath covering the axons and glial
      cells in between them. The system simulates the Brownian motion of molecules to
      extract diffusion data. We perform our experiment for progressive stages of
      demyelination and demonstrate its effect on DTI measurements.

PMID- 29060660
TI  - A portable, low-cost, 3D-printed main magnetic field system for magnetic imaging.
AB  - In this paper, a portable, low-cost, 3D-printed system for main magnetic field is
      proposed to suggest a solution for accessibility problems of current magnetic
      imaging systems, e.g. MRI scanner, their size and cost. The system consists of
      twelve pairs of NdFeB N35 permanent magnets arranged in a Halbach array in a 3D
      printed, cylindrical container based on FEM simulation results by COMSOL
      Multiphysics 4.4b. Its magnetic field homogeneity and field strength were
      measured by Hall sensors, WSH-135 XPAN2 by Wilson Semiconductor, and the
      container was printed by 3DISON H700 by Rokit. The system generated a 5-mm
      imaging quality FOV and main magnetic field of 120 mT with a 12 % error in the
      field strength. Also, a hundred dollar was enough for the manufacture of the
      system with a radius of 6 cm and height of 10 cm. Given the results, I believe
      the system will be useful for some magnetic imaging applications, e.g. EPRI and
      low-field MRI.

PMID- 29060659
TI  - Multi-view collaborative segmentation for prostate MRI images.
AB  - Prostate delineation from MRI images is a prolonged challenging issue partially
      due to appearance variations across patients and disease progression. To address
      these challenges, our proposed collaborative method takes into account the
      computed multiple label-relevance maps as multiple views for learning the optimal
      boundary delineation. In our method, we firstly extracted multiple label
      relevance maps to represent the affinities between each unlabeled pixel to the
      pre-defined labels to avoid the selection of handcrafted features. Then these
      maps were incorporated in a collaborative clustering to learn the adaptive
      weights for an optimal segmentation which overcomes the seeds selection
      sensitivity problems. The segmentation results were evaluated over 22 prostate
      MRI patient studies with respect to dice similarity coefficient (DSC), absolute
      relative volume difference (ARVD) and average symmetric surface distance (ASSD)
      (mm). The results and t-Test demonstrated that the proposed method improved the
      segmentation accuracy and robustness and the improvement was statistically
      significant.

PMID- 29060661
TI  - Accelerated magnetic resonance spectroscopy with Vandermonde factorization.
AB  - Multi-dimensional magnetic resonance spectroscopy is an important tool for
      studying molecular structures, interactions and dynamics in bio-engineering. The
      data acquisition time, however, is relatively long and non-uniform sampling can
      be applied to reduce this time. To obtain the full spectrum,a reconstruction
      method with Vandermonde factorization is proposed. This method explores the
      general signal property in magnetic resonance spectroscopy: Its time domain
      signal is approximated by a sum of a few exponentials. Results on synthetic and
      realistic data show that the new approach can achieve faithful spectrum
      reconstruction and outperforms state-of-the-art low rank Hankel matrix method.

PMID- 29060663
TI  - Inkjet-printed gold nanorods using biocompatible polyelectrolyte layer-by-layer
      coating for patterned photothermal applications.
AB  - Photothermal effect using biocompatible nanoparticles with near infrared
      wavelength light is a versatile tool in biomedical applications due to the
      temperature sensitivity of cells and good penetrability of the light through many
      biological systems. However, precise patterning of the nanoparticles on biochips
      to control the location and intensity of the photothermal effect requires
      suitable fabrication methods. In this report, we show that inkjet printing of
      aqueous nanoparticle solution on polyelectrolyte layer-by-layer coated substrates
      enables micron-scale patterning of gold nanorods, and thus application of
      photothermal effect with good control.

PMID- 29060662
TI  - A novel 3D-printed mechanical actuator using centrifugal force for magnetic
      resonance elastography.
AB  - Magnetic resonance elastography (MRE) is a technique for the quantification of
      tissue stiffness during MR examinations. It requires consistent methods for
      mechanical shear wave induction to the region of interest in the human body to
      reliably quantify elastic properties of soft tissues. This work proposes a novel
      3D-printed mechanical actuator using the principle of centrifugal force for wave
      induction. The driver consists of a 3D-printed turbine vibrator powered by
      compressed air (located inside the scanner room) and an active driver controlling
      the pressure of inflowing air (placed outside the scanner room). The generated
      force of the proposed actuator increases for higher actuation frequencies as
      opposed to conventionally used air cushions. There, the displacement amplitude
      decreases with increasing actuation frequency resulting in a smaller signal-to
      noise ratio. An initial phantom study is presented which demonstrates the
      feasibility of the actuator for MRE. The wave-actuation frequency was regulated
      in a range between 15 Hz and 60 Hz for force measurements and proved sufficiently
      stable (+/- 0.3 Hz) for any given nominal frequency. The generated forces depend
      on the weight of the eccentric unbalance within the turbine and ranged between
      0.67 N to 2.70 N (for 15 Hz) and 3.09 N to 7.77 N (for 60 Hz). Therefore, the
      generated force of the presented actuator increases with rotational speed of the
      turbine and offers an elegant solution for sufficiently large wave actuation at
      higher frequencies. In future work, we will investigate an optimal ratio of the
      weight of unbalance to the size of turbine for appropriately large but tolerable
      wave actuation for a given nominal frequency.

PMID- 29060664
TI  - A system for finger tremor quantification in patients with Parkinson's disease.
AB  - The current diagnosis of Parkinson's disease (PD) is based on a subjective
      assessment by the specialist. The monitoring of the tremor that presents in the
      hand index fingers in a patient with Parkinson's is one of the most important
      parameters to diagnose the evolution of the disease in an objective manner. This
      research analyze the tremor in the hand index fingers of patients with PD with
      medication and without medication. A sensor based in a triaxial accelerometer was
      used to acquire the data produced by the acceleration changes of parkinsonian
      tremor in the case of three activities: postural tremor, action tremor and rest
      tremor. Acquired data were processed in Matlab; the data were filtered and the
      spectral power density (PSD) was estimated with the Burg periodogram. It has been
      verified that the system presented in this article can accurately detect the
      parkinsonian tremors of the patients evaluated, additionally has been found that
      with the medication the tremors do not disappear completely, these remained with
      the same frequencies of PD but with a very small amplitude.

PMID- 29060665
TI  - Robust motion artefact resistant circuit for calculation of Mean Arterial
      Pressure from pulse transit time.
AB  - Cuff-less and non-invasive methods of Blood Pressure (BP) monitoring have faced a
      lot of challenges like stability, noise, motion artefact and requirement for
      calibration. These factors are the major reasons why such devices do not get
      approval from the medical community easily. One such method is calculating Blood
      Pressure indirectly from pulse transit time (PTT) obtained from electrocardiogram
      (ECG) and Photoplethysmogram (PPG). In this paper we have proposed two novel
      analog signal conditioning circuits for ECG and PPG that increase stability,
      remove motion artefacts, remove the sinusoidal wavering of the ECG baseline due
      to respiration and provide consistent digital pulses corresponding to blood
      pulses/heart-beat. We have combined these two systems to obtain the PTT and then
      correlated it with the Mean Arterial Pressure (MAP). The aim was to perform major
      part of the processing in analog domain to decrease processing load over
      microcontroller so as to reduce cost and make it simple and robust. We have found
      from our experiments that the proposed circuits can calculate the Heart Rate (HR)
      with a maximum error of ~3.0% and MAP with a maximum error of ~2.4% at rest and
      ~4.6% in motion.

PMID- 29060666
TI  - A wearable, EEG-based massage headband for anxiety alleviation.
AB  - In this work, we would like to discuss our findings obtained from the newly
      proposed hardware design for anxiety detection and its mitigation where a
      subject's state of mind is identified from the neurological data retrieved. A
      feedback-based network implemented for stress alleviation mainly comprises of a
      pair of massage motors and RGB light-emitting diode (LED) that activate during
      conditions of stress detected, a custom-made Electroencephalography (EEG)-sensor
      and a massage motor circuit both functioning on an Arduino driven platform. The
      skin electrodes facilitate a hassle-free retrieval of beta waves from the frontal
      areas that are transmitted wirelessly by a Bluetooth console to a computer post
      signal amplification and filtration. Rising amplitudes of beta signals that are
      associated to anxiety have been successfully tackled in three out of four
      subjects by suppressing the high values due to the massage motor therapy
      introduced. The motors on sensing high amplitude values exceeding the pre-set
      threshold limits during the three experiment trials rotate smoothly thus helping
      one to relax and guaranteeing a higher work performance.

PMID- 29060667
TI  - TongueToSpeech (TTS): Wearable wireless assistive device for augmented speech.
AB  - Speech is an important aspect of human communication; individuals with speech
      impairment are unable to communicate vocally in real time. Our team has developed
      the TongueToSpeech (TTS) device with the goal of augmenting speech communication
      for the vocally impaired. The proposed device is a wearable wireless assistive
      device that incorporates a capacitive touch keyboard interface embedded inside a
      discrete retainer. This device connects to a computer, tablet or a smartphone via
      Bluetooth connection. The developed TTS application converts text typed by the
      tongue into audible speech. Our studies have concluded that an 8-contact point
      configuration between the tongue and the TTS device would yield the best user
      precision and speed performance. On average using the TTS device inside the oral
      cavity takes 2.5 times longer than the pointer finger using a T9 (Text on 9 keys)
      keyboard configuration to type the same phrase. In conclusion, we have developed
      a discrete noninvasive wearable device that allows the vocally impaired
      individuals to communicate in real time.

PMID- 29060668
TI  - One size fits all electronics for insole-based activity monitoring.
AB  - Footwear based wearable sensors are becoming prominent in many areas of
      monitoring health and wellness, such as gait and activity monitoring. In our
      previous research we introduced an insole based wearable system SmartStep, which
      is completely integrated in a socially acceptable package. From a manufacturing
      perspective, SmartStep's electronics had to be custom made for each shoe size,
      greatly complicating the manufacturing process. In this work we explore the
      possibility of making a universal electronics platform for SmartStep - SmartStep
      3.0, which can be used in the most common insole sizes without modifications. A
      pilot human subject experiments were run to compare the accuracy between the one
      size fits all (SmartStep 3.0) and custom size SmartStep 2.0. A total of ~10 hours
      of data was collected in the pilot study involving three participants performing
      different activities of daily living while wearing SmartStep 2.0 and SmartStep
      3.0. Leave one out cross validation resulted in a 98.5% average accuracy from
      SmartStep 2.0, while SmartStep 3.0 resulted in 98.3% accuracy, suggesting that
      the SmartStep 3.0 can be as accurate as SmartStep 2.0, while fitting most common
      shoe sizes.

PMID- 29060669
TI  - Electrical bioimpedance spectroscopy as biosensor technique to identify cells
      lineages and cell differentiation process.
AB  - The identification and characterization of diverse cells types and cell
      differentiation process requires complex techniques as flow cytometry,
      immunocytochemistry and the exploration of molecular markers; such techniques
      require infrastructure and qualified personnel. The objective of this study was
      to analyze the use of Electrical Bioimpedance Spectroscopy (EBIS) measurements as
      a non-complex alternative technique to identify populations of undifferentiated
      mouse Pluripotent Stem Cells (mPSCs), Mouse Embryonic Fibroblasts (MEFs) and the
      differentiation process from preadipocytes (3T3-L1) to mature adipocytes. EBIS
      measurements were compared in populations of cells which were characterized
      previously using microscopy. The results indicate that EBIS technique has a
      potential sensitivity at certain frequency range to discriminate between both
      evaluated cell populations and some differentiation process. Additional studies
      with different concentrations to evaluate quantitatively the sensitivity and
      specificity of the proposed technique are recommended.

PMID- 29060670
TI  - Finite-element modelling and preliminary validation of microneedle-based
      electrodes for enhanced tissue electroporation.
AB  - This paper investigates the use of microneedle-based electrodes for enhanced
      testis electroporation, with specific application to the production of transgenic
      mice. During the design phase, finite-element software has been used to construct
      a tissue model and to compare the relative performance of electrodes employing a)
      conventional flat plates, b) microneedle arrays, and c) invasive needles. Results
      indicate that microneedle-based electrodes can achieve internal tissue field
      strengths which are an order of magnitude higher than those generated using
      conventional flat electrodes, and which are comparable to fields produced using
      invasive needles. Using a double-sided etching process, conductive microneedle
      arrays were then fabricated and used in prototype electrodes. In a series of
      mouse model experiments involving injection of a DNA vector expressing Green
      Fluorescent Protein (GFP), the performance of flat and microneedle electrodes was
      compared by measuring GFP expression after electroporation. The main finding,
      supported by experimental and simulated data, is that use of microneedle-based
      electrodes significantly enhanced electroporation of testis.

PMID- 29060671
TI  - EM fields comparison between planar vs. solenoidal MUMS coil designs for nerve
      stimulation.
AB  - Micro-magnetic stimulation (MUMS) is an emerging neurostimulation technology that
      promises to revolutionize the therapeutic stimulation of the human nervous
      system. MUMS uses sub-millimeter sized coils that can be implemented in the
      central nervous system to elicit neuronal activation using magnetically induced
      electric currents. By their microscopic size, MUMS coils can be acutely implanted
      in deep brain structures to deliver therapeutic stimulation with effects
      analogous to those achieved by state-of-the-art deep brain stimulation (DBS).
      However, MUMS technology has inherent advantages that make it particularly
      appealing for clinical applications. Specifically, MUMS induces a focal electric
      current in the tissue, limiting the extent of activation to a few hundred
      microns. We recently demonstrated the feasibility of using MUMS to elicit
      neuronal activation in vitro [1], as well as the possibility of activating
      neuronal circuitry on the system level in rodents [2]. As MUMS is a novel
      technology, its mechanism(s) of nerve activation, induced field characteristics,
      and optimum topological features are yet to be explored. In this regard,
      numerical simulations play a crucially important role, because they provide an
      insight into spatial distribution of induced electric fields, which in turn,
      dictate the dynamics of nerve stimulation. Here we report results of numerical
      simulations to predict the nerve-stimulation performance of different MUMS
      geometries.

PMID- 29060672
TI  - Design and construction of a synthetic E. coli protease inhibitor detecting
      biomachine.
AB  - Protease inhibitors (PIs) have been used to treat various types of symptoms or
      diseases. However, current PIs block the protease activity by targeting the
      protease active site which has been shown to be sensitive to the off-target
      effect due to crossreactivity with protease homologues. An alternative approach
      to inhibiting protease activity is to target the substrate, specifically by
      blocking the substrate cleavage site. We propose to employ synthetic biology
      approach to create a synthetic E. coli to be used as a protease inhibitor
      detecting biomachine that can effectively isolate intrabodies, a new generation
      of protease inhibitor drug. The in vivo selection system, comprised of three
      biological devices, i.e., protease activity detector, protease generator and
      protease blocking devices, is based on the ability to transport folded protein of
      the E. coli twin-arginine translocation (Tat) pathway and antibiotic resistance
      of TEM-1 beta-lactamase (Bla) using as reporter protein. By linking protease
      degradation to antibiotic resistance, we can isolate the suitable intrabodies
      simply by plating cells containing appropriate devices on solid agar containing
      beta-lactam ring antibiotics. As a proof of concept, we applied a previously
      isolated HIV-1 p17 intrabody (scFvp17) that binds to the C-terminus of HIV-1
      matrix protein (p17) to our synthetic E. coli. This work demonstrated that
      binding of scFvp17 to its epitope on p17 can physically interfere with HIV-1
      protease activity and inhibit proteolytic cleavage at the p17Deltap24 cleavage
      site when expressed in the designed format. The device was optimized by varying
      plating conditions such as incubation temperatures, induction levels, and
      Carbenicillin concentrations which was used as selection pressure. The
      feasibility of this assay has opened the door to protease inhibitor selection
      which can be used for various applications such as optimization of the current
      protease inhibitors and selection of new ones.

PMID- 29060673
TI  - Determination of Red Blood Cell fatigue using electrodeformation.
AB  - In this work, we used electrodeformation (ED) [1] as a new strategy to evaluate
      the fatigue of healthy human Red Blood Cells (RBCs). Using dielectrophoresis
      (DEP) forces, we submitted RBCs to a series of elongation and relaxation cycles
      to model their mechanical stress in the blood circulation and we used their
      relaxation time as a marker to evaluate their fatigue. In this paper, we first
      investigated the dependency of the RBC mechanical response upon the experimental
      parameters, such as the viscosity etaout of the external medium, the amplitude
      DeltaV of the applied voltage, the duration of the solicitation tsol, the number
      of solicitations N as well as the resting time trest between two solicitations.
      The impact of these parameters was evaluated through the analysis of both RBC
      deformation index D and relaxation time tau. Finally, the optimization of these
      parameters was used to monitor RBC fatigue.

PMID- 29060674
TI  - Analysis of dielectrophoresis based 3D-focusing in microfluidic devices with
      planar electrodes.
AB  - This article models a dielectrophoresis based approach for achieving 3D focusing,
      of micro-scale objects, in microfluidic devices. The microfluidic device employs
      four planar electrodes; two electrodes each on the top and bottom surface of the
      microchannel and each slightly protrude into the microchannel. Each electrode
      establishes electric field with the neighboring electrode on the same and
      opposite surfaces. The dielectrophoretic force pushes the micro-scale objects
      both the directions transverse to the flow direction to achieve the desired 3D
      focusing. The developed model accounts for various forces such as that associated
      with inertia, sedimentation, drag, and dielectrophoresis. Finite difference
      method is used for calculating the electric field and dielectrophoretic force as
      well as the displacements of micro-scale objects in the microchannel. Several
      geometric and operating parameters influence the trajectory of micro-scale
      objects. There exists a threshold voltage beyond which there is no increase in
      levitation height.

PMID- 29060675
TI  - Effect of laser diode light irradiation on growth capability of human hair
      follicle dermal papilla cells.
AB  - Low level laser therapy is widely used to relieve pain and inflammation, and to
      restore cellular functions. The photons of light are absorbed by mitochondria in
      cells, leading to an increase in the production of adenosine triphosphate (ATP),
      nitric oxide release, blood flow, and reactive oxygen species (ROS). This study
      proposed the use of a laser diode array at 808 nm to stimulate the proliferation
      and to activate the functions of dermal papilla cells, which were an important
      part of the hair growth cycle. These cells were isolated from human hair
      follicles and were exposed to 808 nm light at various doses from 0.5, 1, 2.5, 4,
      and 6 J/cm2. The rate of cell proliferation and the gene expression profile of
      dermal papilla cells were investigated and compared with the control in which the
      cells did not received any light treatment. The growth curves of the dermal
      papilla cells were used to determine the specific growth rates. Higher specific
      growth rates were observed in the cells exposed to laser at doses higher than 0.5
      J/cm2. The effect of the laser light treatment on several gene markers,
      specifically for dermal papilla cells, was evaluated using real-time polymerase
      chain reaction (qPCR). Our result shows that collagen type 1 (Col1), alkaline
      phosphatase (Alp), and versican (Vcan) did not increase when the cells were
      irradiated by the laser light. Interestingly, sex determining region y-box 2
      (Sox2) gene was up-regulated when 0.5 J/cm2, and 1 J/cm2 light was used, while an
      increase in the level of fibroblast growth factor 7 (Fgf7) gene was observed with
      light irradiation at 0.5 J/cm2, 1 J/cm2, 2.5 J/cm2, and 4 J/cm2. Too high
      irradiation dose was shown to yield no effect on the gene expression of dermal
      papilla cells.

PMID- 29060676
TI  - Gamma-variate modeling of indicator dilution curves in electrical impedance
      tomography.
AB  - Electrical impedance tomography (EIT) is a non-invasive imaging technique, that
      can be used to monitor regional lung ventilation (V) in intensive care units
      (ICU) at bedside. This work introduces a method to extract regional lung
      perfusion (Q) from EIT image streams in order to quantify regional gas exchange
      in the lungs. EIT data from a single porcine animal trial, recorded during
      injection of a contrast agent (NaCl 10%) into a central venous catheter (CVC),
      are used for evaluation. Using semi-negative matrix factorization (Semi-NMF) a
      set of source signals is extracted from the data. A subsequent non-linear fit of
      a gamma-variate model to the source signals results in model signals, describing
      contrast agent flow through the cardio-pulmonary system. A linear fit of the
      model signals to the EIT image stream then yields functional images ofQ.
      Additionally, a pulmonary transit function (PTF) and parameters, such as mean
      transit time (MTT), time to peak (TTP) and area under curve (AUC) are derived. In
      result, EIT was used to track changes of regional lung ventilation to perfusion
      ratio (V/Q) during changes of positive end-expiratory pressure (PEEP).
      Furthermore, correlations of MTT and AUC with cardiac output (CO) indicate that
      CO measurement by EIT might be possible.

PMID- 29060677
TI  - Localization of stereo-electroencephalography signals using a finite difference
      complete electrode model.
AB  - Surgical intervention in epilepsy aims to eliminate seizures in refractory
      patients by resecting the tissue responsible for seizure onset. Stereo
      electroencephalography (sEEG) provides highly accurate but invasive
      electrophysiological measurements using narrow multi-contact electrodes implanted
      stereotactically through small holes in the skull. However, the three dimensional
      nature of sEEG measurements make observed seizure onsets difficult to associate
      with physical cortical regions. Three dimensional source localization from sEEG
      measurements can improve the interpretation of this data, but requires more
      accurate modeling as compared to localization from scalp EEG. Here, we present a
      finite difference approach that models the contact impedance and physical extent
      of each electrode (the so-called complete electrode model), to localize brain
      electrical activity from sEEG measurements. We applied this model to MRI and CT
      in a patient with intractable epilepsy, and reconstructed activity associated
      with multiple types of recurrent ictal spikes observed in sEEG. Independently,
      the neurosurgeon resected the clinically determined seizure focus, creating a
      resection cavity, and rendering the patient free of seizures. Our localization
      placed the seizure focus at a focal region in the occipital lobe, entirely
      contained within the resection region.

PMID- 29060678
TI  - ICA on sensor or source data: A comparison study in deriving resting state
      networks from EEG.
AB  - Resting state networks (RSNs) are human brain networks formed by spontaneous
      activity fluctuations in distributed brain regions when people are in task-free
      and awake state. RSNs have been so far extensively studied using functional
      magnetic resonance imaging (fMRI). Recently, electroencephalography (EEG) and
      magnetoencephalography (MEG) have also been used to derive RSNs, in which
      independent component analysis (ICA) is the key step. In these studies, ICA has
      been either directly applied to recorded data at sensors (sensor-space ICA) or
      estimated source data from sensors using inverse source imaging techniques
      (source-space ICA). Both sensor-space and source-space ICAs have demonstrated the
      capability in finding RSNs from EEG/MEG data and their results showed strong
      correlations to fMRI RSNs. However, their performance was hardly compared even
      differences have been observed in their results. In the present study, we
      compared the source-space and sensor-space ICAs in reconstructing spatial,
      temporal and spectral features of RSNs in both simulated and real EEG data.
      Results from simulated data indicated that the source-space ICA has better
      performance in reconstructing spatial, temporal, and spectral feature of RSNs.
      Results from resting-sate EEG data in seven healthy participants also showed the
      difference between two procedures and, through the comparison with RSN templates
      constructed from fMRI data, the source-space ICA indicated relatively better
      performance than the sensor-space ICA.

PMID- 29060679
TI  - Spatial regularization based on dMRI to solve EEG/MEG inverse problem.
AB  - In this paper, we present a new approach to reconstruct dipole magnitudes of a
      distributed source model for magnetoencephalographic (MEG) and
      electroencephalographic (EEG). This approach is based on the structural
      homogeneity of the cortical regions which are obtained using diffusion MRI
      (dMRI). First, we parcellate the cortical surface into functional regions using
      structural information. Then, we use a weighting matrix that relates the dipoles'
      magnitudes of sources inside these functional regions. The weights are based on
      the region's structural homogeneity. Results of the simulated and real MEG
      measurement are presented and compared to classical source reconstruction
      methods.

PMID- 29060680
TI  - EEG fluctuations of wake and sleep in mild cognitive impairment.
AB  - Amnestic Mild Cognitive Impairment (aMCI), a condition in which the memory
      functions of cognition are significantly impaired, is an established risk factor
      for Alzheimer's disease. Electroencephalography (EEG) is a tool capable of
      measuring the dynamics of the brain's neural networks, and is thus an important
      means in analysis and understanding of aMCI. In this proof-of-concept study, we
      compared the brain activation patterns of ten aMCI subjects with those of four
      healthy subjects during sleep by employing a 64-channel EEG data collection
      system. The power spectrum was analyzed to identify sleep stages, while spectral
      topography and source imaging techniques were employed to study the fluctuating
      patterns of the brain. Results of this study show an increase in activation power
      across all sleep stages in the delta and theta frequency bands alongside a
      decrease in alpha band activity for aMCI subjects. Source imaging analysis of the
      resting EEG identified default mode network, which becomes decoupled as sleep
      stages deepen. In the proof-of-concept study, our exploratory analysis
      demonstrated the feasibility of imaging dynamic network organization using EEG in
      aMCI.

PMID- 29060681
TI  - Computation of Surface Laplacian for tri-polar ring electrodes on high-density
      realistic geometry head model.
AB  - Neural activity inside the human brain generate electrical signals that can be
      detected on the scalp. Electroencephalograph (EEG) is one of the most widely
      utilized techniques helping physicians and researchers to diagnose and understand
      various brain diseases. Due to its nature, EEG signals have very high temporal
      resolution but poor spatial resolution. To achieve higher spatial resolution, a
      novel tri-polar concentric ring electrode (TCRE) has been developed to directly
      measure Surface Laplacian (SL). The objective of the present study is to
      accurately calculate SL for TCRE based on a realistic geometry head model. A
      locally dense mesh was proposed to represent the head surface, where the local
      dense parts were to match the small structural components in TCRE. Other areas
      without dense mesh were used for the purpose of reducing computational load. We
      conducted computer simulations to evaluate the performance of the proposed mesh
      and evaluated possible numerical errors as compared with a low-density model.
      Finally, with achieved accuracy, we presented the computed forward lead field of
      SL for TCRE for the first time in a realistic geometry head model and
      demonstrated that it has better spatial resolution than computed SL from classic
      EEG recordings.

PMID- 29060682
TI  - Independent component analysis-based spatial filtering improves template-based
      SSVEP detection.
AB  - This study proposes a new algorithm to detect steady-state visual evoked
      potentials (SSVEPs) based on a template-matching approach combined with
      independent component analysis (ICA)-based spatial filtering. In recent studies,
      the effectiveness of the template-based SSVEP detection has been demonstrated in
      a high-speed brain-computer interface (BCI). Since SSVEPs can be considered as
      electroencephalogram (EEG) signals generated from underlying brain sources
      independent from other activities and artifacts, ICA has great potential to
      enhance the signal-to-noise ratio (SNR) of SSVEPs by separating them from
      artifacts. This study proposes to apply the ICA-based spatial filters to test
      data and individual templates obtained by averaging training trials, and then to
      use the correlation coefficients between the filtered data and templates as
      features for SSVEP classification. This study applied the proposed method to a 40
      class SSVEP dataset to evaluate its classification accuracy against those
      obtained by conventional canonical correlation analysis (CCA)- and extended CCA
      based methods. The study results showed that the ICA-based method outperformed
      the other methods in terms of the classification accuracy. Furthermore, its
      computational time was comparable to the CCA-based method, and was much shorter
      than that of the extended CCA-based method.

PMID- 29060683
TI  - Using monkey hand exoskeleton to explore finger passive joint movement response
      in primary motor cortex.
AB  - While neurons in primary motor cortex (M1) have been shown to respond to sensory
      stimuli, exploration of this phenomenon has proven challenging. Accurate and
      repeatable presentation of sensory inputs is difficult. Here, we describe a novel
      paradigm to study response to joint motion and fingertip force. We employed a
      custom exoskeleton to drive index finger metacarpophalangeal joint (MCP) of a
      macaque to follow sinusoid trajectories at 4 different frequencies (0.2, 0.5, 1,
      2Hz) and 2 movement ranges (68.4, 34.2 degrees). We highlight results of a
      specific M1 unit that displayed sensitivity to direction (more active during
      flexion than extension), frequency (greater firing rate at higher frequencies),
      and movement amplitude (higher rate at larger amplitude). Joint movement
      trajectories were accurately reconstructed from this single unit with mean R2
      =0.64 +/- 0.13. The exoskeleton holds promise for examination of sensory
      feedback. In addition, it can be used as an external device controlled by a brain
      machine interface (BMI) system. The proprioceptive related units in M1 may
      contribute to improving BMI control performance.

PMID- 29060684
TI  - Specific CA3 neurons decode neural information of dentate granule cells evoked by
      paired-pulse stimulation in co-cultured networks.
AB  - CA3 and dentate gyrus (DG) neurons are cultured in two-chamber devices on multi
      electrode arrays (MEAs) and connected via micro-tunnels. In order to evoke time
      locked activity, paired-pulse stimulation is applied to 22 different sites and
      repeated 25 times in each well in 5 MEA co-cultures and results compared to CA3
      CA3 and DG-DG networks homologous controls. In these hippocampal sub-regions, we
      focus on the mechanisms underpinning a network's ability to decode the identity
      of site specific stimulation from analysis of evoked network responses using a
      support vector machine classifier. Our results indicate that a pool of CA3
      neurons is able to reliably decode the identity of DG stimulation site
      information.

PMID- 29060685
TI  - Information transmission in the primary visual cortex of retinal degenerated
      rats.
AB  - To study the information transmission in the primary visual cortex (V1) of
      retinal degenerated (RD) models, wild type (WT) and RD rats were used in the
      experiments. The neural response in V1 was recorded extracellularly while the
      flicker with varied intensity levels was given as the visual stimulus. The mutual
      information (MI) and normalized mutual information (NMI) were determined for
      every isolated neuron, in order to quantify the amount and efficiency of
      information transmission in V1 of both control and experimental groups. The
      results showed that, on one hand, the RD group manifested relatively decreased
      information transmission amount and efficiency, comparing to the control group;
      On the other hand, it also implied that even for the RD rat, whose early stage of
      visual system was impaired, the later parts of visual system, especially the
      primary visual cortex, were still able to capture the information on visual
      stimulation, thus they can be utilized for restoring the visual ability, for
      example, via the visual prosthesis. In addition, it certainly requires more
      experiments for testifying and extending those results and implications.

PMID- 29060686
TI  - Sparse coding of ECoG signals identifies interpretable components for speech
      control in human sensorimotor cortex.
AB  - The concept of sparsity has proven useful to understanding elementary neural
      computations in sensory systems. However, the role of sparsity in motor regions
      is poorly understood. Here, we investigated the functional properties of sparse
      structure in neural activity collected with high-density electrocorticography
      (ECoG) from speech sensorimotor cortex (vSMC) in neurosurgical patients. Using
      independent components analysis (ICA), we found individual components
      corresponding to individual major oral articulators (i.e., Coronal Tongue, Dorsal
      Tongue, Lips), which were selectively activated during utterances that engaged
      that articulator on single trials. Some of the components corresponded to
      spatially sparse activations. Components with similar properties were also
      extracted using convolutional sparse coding (CSC), and required less data pre
      processing. Finally, individual utterances could be accurately decoded from vSMC
      ECoG recordings using linear classifiers trained on the high-dimensional sparse
      codes generated by CSC. Together, these results suggest that sparse coding may be
      an important framework and tool for understanding sensory-motor activity
      generating complex behaviors, and may be useful for brain-machine interfaces.

PMID- 29060687
TI  - A new EMG-based index towards the assessment of elbow spasticity for post-stroke
      patients.
AB  - The commonly used method for grading spasticity in clinical applications is
      Modified Ashworth Scale (MAS). The MAS-based method depends on the subjective
      evaluations and the experience of physicians, which may lead to imprecise and
      inconsistent evaluations. In this study, we propose a novel index (A-ApA, which
      was calculated with the root mean square (RMS) of agonist muscle activity by the
      mean between the RMS of agonistic and antagonistic muscle activations extracted
      from surface electromyography (sEMG) signals to quantitatively assess elbow
      spasticity. 39 post-stroke patients with elbow spasticity caused by hemiplegia
      participated in the experiments, and their elbow spasticity was assessed with MAS
      by one experienced physiotherapist. Patients were thereafter divided into four
      groups according to the MAS scales. The sEMG signals were recorded simultaneously
      on the patients' biceps and triceps when they extended or bended their elbows
      passively. The correlations between MAS and RMS of sEMG signals as well as the
      newly proposed index were calculated. The results demonstrated that the
      correlation between the MAS and the sEMG-based index in the assessment of elbow
      spasticity was significant. This suggests that the EMG-based index would be
      helpful for the assessment of spasticity..

PMID- 29060688
TI  - gamAID: Greedy CP tensor decomposition for supervised EHR-based disease
      trajectory differentiation.
AB  - We propose gamAID, an exploratory, supervised nonnegative tensor factorization
      method that iteratively extracts phenotypes from tensors constructed from medical
      count data. Using data from diabetic patients who later on get diagnosed with
      chronic kidney disorder (CKD) as well as diabetic patients who do not receive a
      CKD diagnosis, we demonstrate the potential of gamAID to discover phenotypes that
      characterize patients who are at risk for developing a disease.

PMID- 29060690
TI  - Exploration of unsupervised feature selection methods to predict chronological
      age of individuals by utilising CpG dinucleotics from whole blood.
AB  - Identification of the age of individuals from epigenetic biomarkers can reveal
      vital information for criminal investigation, disease prevention, and extension
      of life. DNA methylation changes are highly associated with chronological age and
      the process of disease development. Computational methods such as clustering,
      feature selection and regression can be utilised to construct quantitative model
      of aging. In this study, we utilised 473034 CpG biomarkers from whole blood of
      656 individuals aged 19 to 101 to construct predictive models and we treat the
      development of this age predictive model as extremely high-dimensional regression
      problem that is relatively understudied. Unlike semi-supervised and supervised
      feature selection methods, unsupervised feature selection methods are generally
      good at removing irrelevant features that can act as noise. In this study, along
      with the entire feature set, four different unsupervised feature selection
      methods (USFSMs) are therefore considered for the quantitative prediction of
      human ages. Since USFSMs are independent of any predictive method, support vector
      regression is then used to evaluate the prediction performances of the
      unsupervised feature selection methods. We proposed a novel k-means based
      unsupervised feature selection method to predict human ages by utilising CpG
      dinucleotides. Experimental results have validated the effectiveness of the
      proposed method as the optimum number of the CpG dinucleotides is found to be
      only 41 that corresponds to only 0.0087% of the entire feature space. To the best
      of our knowledge, this is the first study that presents exploration and
      comprehensive comparison of USFSMs in very high dimensional regression problems,
      particularly in epigenetic biomedical domain for the prediction of chronological
      age from changes in DNA methylation.

PMID- 29060689
TI  - A computational approach for the estimation of heart failure patients status
      using saliva biomarkers.
AB  - The aim of this work is to present a computational approach for the estimation of
      the severity of heart failure (HF) in terms of New York Heart Association (NYHA)
      class and the characterization of the status of the HF patients, during
      hospitalization, as acute, progressive or stable. The proposed method employs
      feature selection and classification techniques. However, it is differentiated
      from the methods reported in the literature since it exploits information that
      biomarkers fetch. The method is evaluated on a dataset of 29 patients, through a
      10-fold-cross-validation approach. The accuracy is 94 and 77% for the estimation
      of HF severity and the status of HF patients during hospitalization,
      respectively.

PMID- 29060691
TI  - Wrapper method for feature selection to classify cardiac arrhythmia.
AB  - Efficient monitoring of cardiac patients can save tremendous amount of lives.
      Cardiac disease prediction and classification has gained utmost significance in
      this regard during the past few years. This paper presents a predictive model for
      classification of arrhythmias. The model works by selecting best features using
      wrapper algorithm around random forest, followed by implementing various machine
      learning classifiers on the selected features. Cardiac arrhythmia dataset from
      University of California, Irvine (UCI) machine learning repository has been used
      for the experimental purpose. After normalizing the data, repeated cross
      validation with 10 folds is applied on support vector machine (SVM), K nearest
      neighbor (KNN), Naive Bayes, random forest, and Multi-Layer perceptron (MLP). The
      experimental results demonstrate that MLP beats other classifiers by achieving an
      average accuracy of 78.26%, while accuracies calculated for KNN and SVM are 76.6%
      and 74.4% respectively, outperforming the accuracies of previous models.

PMID- 29060692
TI  - Prediction and imputation in irregularly sampled clinical time series data using
      hierarchical linear dynamical models.
AB  - Clinical time series, comprising of repeated clinical measurements provide
      valuable information of the trajectory of patients' condition. Linear dynamical
      systems (LDS) are used extensively in science and engineering for modeling time
      series data. The observation and state variables in LDS are assumed to be
      uniformly sampled in time with a fixed sampling rate. The observation sequence
      for clinical time series is often irregularly sampled and LDS do not model such
      data well. In this paper, we develop two LDS-based models for irregularly sampled
      data. The key idea is to incorporate a temporal difference variable within the
      state equations of LDS whose parameters are estimated using observed data. Our
      models are evaluated on prediction and imputation tasks using real irregularly
      sampled clinical time series data and are found to outperform state-of-the-art
      techniques.

PMID- 29060693
TI  - Identifying frauds and anomalies in Medicare-B dataset.
AB  - Healthcare industry is growing at a rapid rate to reach a market value of $7
      trillion dollars world wide. At the same time, fraud in healthcare is becoming a
      serious problem, amounting to 5% of the total healthcare spending, or $100
      billion dollars each year in US. Manually detecting healthcare fraud requires
      much effort. Recently, machine learning and data mining techniques are applied to
      automatically detect healthcare frauds. This paper proposes a novel PageRank
      based algorithm to detect healthcare frauds and anomalies. We apply the algorithm
      to Medicare-B dataset, a real-life data with 10 million healthcare insurance
      claims. The algorithm successfully identifies tens of previously unreported
      anomalies.

PMID- 29060694
TI  - A computational model of myocardial microcirculation including interstitial flow.
AB  - Contributions of interstitial fluid (ISF) flow within the myocardial
      microcirculation is not well understood despite its importance due to
      difficulties in measurements. For analysing a contribution of interstitial fluid
      flow within myocardial microcirculation, we developed a computational model of
      myocardial microcirculation by introducing convection by the ISF flow into an
      existing myocardial microcirculation model, and performed simulations with varied
      ISF flows in normal and hypoperfusion conditions. Simulation results show that
      the ISF flow has a contribution only with low capillary flow. This might suggest
      partial comensation of oxygen supply by the ISF flow under ischemic conditions.

PMID- 29060695
TI  - PWPSim: A new simulation tool of pulse wave propagation in the human arterial
      tree.
AB  - Hemodynamic simulation enhances investigations of pulse wave propagation
      phenomena and enables validation of new methods of pulse wave analysis. However,
      such simulation systems or tools are not readily available nor easily accessible.
      In this study, a new simulation tool of pulse wave propagation in the human
      arterial tree was developed based on a transmission line model (TLM). This paper
      describes the theory of TLM of the human arterial tree used by this simulation.
      The results are a display of the main functions and simulation results of this
      tool. This tool allows simulation of pulse wave propagation with capability to
      change the range of parameters, such as heart rate, mean flow and left
      ventricular ejection time, body height, arterial radius and wall thickness,
      arterial viscoelasticity, peripheral resistance and compliance. It also accounts
      for the nonlinear elasticity of arteries. The simulation results are displayed as
      2D and 3D figures of blood pressure and flow waveforms, input impedance and
      pressure transfer function between aorta and femoral artery, including systolic
      blood pressure, diastolic blood pressure, pulse pressure, carotid-femoral pulse
      wave velocity, brachial-ankle pulse wave velocity and ankle-brachial index. It is
      a useful and interactive simulation tool of pulse wave propagation in the
      systematic arterial tree.

PMID- 29060696
TI  - Global sensitivity analysis for developing biological models: Application to K+
      channel model in mouse ventricular myocytes.
AB  - Mathematical models of cardiac myocytes are highly nonlinear and involve a large
      number of model parameters. The parameters are estimated using experimental data,
      which are often corrupted by noise and uncertainty. Such uncertainty can be
      propagated onto model parameters during model calibration, which further affects
      model reliability and credibility. In order to improve model accuracy, it is
      important to quantify and reduce the uncertainty in model response resulting from
      parametric uncertainty. Sensitivity analysis is a key technique to investigate
      the significance of parametric uncertainty and its effect on model responses.
      This can identify and rank most sensitive parameters, and evaluate the effect of
      uncertainty on model outputs. In this work, a global sensitivity analysis is
      developed to determine the significance of parametric uncertainty on model
      responses using Sobol indices. This method is applied to nonlinear K+ channel
      models of mouse ventricular myocytes to demonstrate the efficacy of the developed
      algorithm.

PMID- 29060697
TI  - A generic cardiac biventricular fluid-electromechanics model.
AB  - We present a fully-coupled fluid-electromechanics model of the heart using a
      generic biventricular structure to provide a tool for future multiphysics
      interaction studies. A simplified Purkinje fibre structure was embedded within
      the myocardium along with transmural variation of action potential duration to
      obtain realistic activation and relaxation sequences. To ease computational
      requirements, phenomenological action potential and excitation-contraction
      formulations were chosen, and coupled to transverse isotropic hyperelastic
      myocardial material physics. The action potential propagation was discretised
      within the material frame to achieve electromechanical coupling with gap junction
      controlled propagation. Blood haemodynamics was represented by incompressible
      Navier-Stokes equations, whereby, the endocardial displacement deforms the blood
      domain, whilst blood pressure and viscous stress exert load on the myocardium.
      Realistic electrical activation and relaxation sequences were achieved along with
      basic cardiac mechanical properties such as torsion and apex displacement. The
      pressure-volume loops for both ventricles matched known values, and vortex
      formation was noted during the filling phase. The model could facilitate a better
      understanding of multiphysics and biventricular interactions under pathologic
      conditions and help formulate better treatments.

PMID- 29060698
TI  - Effects of island-distribution of mid-cardiomyocytes on ventricular electrical
      excitation associated with the KCNQ1-linked short QT syndrome.
AB  - AIMS: Short QT syndrome (SQTS) is a new genetic disorder of the electrical system
      of the heart. To date, there are six gene mutations in ion channels underlying
      SQTS. However, functional effects of spatial heterogeneities, such as island
      distribution of mid-cardiomyocytes (M island) on ventricular electrical
      excitation in SQTS condition are poorly understood or even not understood at all.
      Therefore, this study used computational modelling to investigate such possible
      effects. METHODS: The spatial heterogeneities of ventricular tissue was studied
      by using ten Tusscher et al. MODEL: The model was modified to simulate changes to
      IKs based on experimental observations of KCNQ1 V307L mutation in SQT2 condition.
      Cell models were coupled to construct a strand tissue, among which 35% were mid
      cardiomyocytes, either distributed in island form or in band form, 25% were
      endocardial (ENDO), and the rest part were epicardial (EPI) cells. RESULTS: In
      simulations, the QT interval was shortened due to the KCNQ1 V307L mutation. The
      model with M band form failed to reproduce a markedly increase in the T-wave
      height. However, the model with M island form was able to produce a markedly
      increased T-wave height with the V307L mutation, matching the major features of
      SQT clinical ECGs. CONCLUSIONS: This study substantiates a causal link between
      the M island and T-wave amplitude in the KCNQ1-linked short QT syndrome.

PMID- 29060699
TI  - Hyperthermia dependence of cardiac conduction velocity in rat myocardium: Optical
      mapping and cardiac near field measurements.
AB  - Hyperthermia during radiofrequency ablation causes reversible and irreversible
      changes of the electrophysiological properties of cardiac tissue. However, the
      mechanisms are incompletely understood. We studied changes of conduction velocity
      (CV) in rat myocardium under hyperthermic conditions from macroscopic to
      microscopic scale by using simultaneous optical mapping and a miniaturized
      electrode array. Atrial preparations from five rats were superfused at tissue
      bath temperatures between 36.7 degrees C and 43.8 degrees C. Optical mapping data
      showed an elevated median CV by 21% when increasing the temperature from 36.7
      degrees C to 42.0 degrees C. CV did not increase above 42.0 degrees C. Electrical
      measurements revealed a similar temperature dependence of CV between 36.7 degrees
      C and 42.0 degrees C, i.e. an increase of median CV by 26%. The consolidation of
      optical and electrical data in this study allowed investigation of excitation
      during global hyperthermia. Macroscopic optical mapping and microscopic
      electrical measurements demonstrated that hyperthermia strongly influenced
      electrical propagation at a microscopic scale.

PMID- 29060700
TI  - An enhanced hybrid tracking-mosaicking approach for surgical view expansion.
AB  - The aim of this work is to overcome the narrow surgical field of view problem in
      minimally invasive surgery. We achieve this by combining multiple views of the
      camera-retractable trocar which can obtain surgical viewpoints different from
      laparoscopic view. However, the accuracy and time are essential factors in this
      process. Therefore, we tend to improve the accuracy of a hybrid tracking
      mosaicking approach which can combine several views at high speed. Two
      improvements are presented and analyzed here. The first improvement utilizes two
      sharping methodologies to enhance the image quality. This enhancement, in turn,
      improves the interest point extraction process and increases the number of
      extracted points. In the second enhancement, the tracking accuracy is improved by
      applying a filtering methodology to select the set of valid flow vectors only.
      This process reduces the tracking error which may accumulate during tracking. The
      experimental evaluation, shows that these improvements enhance the final
      mosaicking accuracy and allows us to construct a more accurate expanded view.

PMID- 29060701
TI  - A low-dimensional representation for individual head geometries.
AB  - In the estimation of individual head geometries for source localization and
      electrical stimulation in neuroelectric investigations and application, mostly
      complex geometrical models are directly extracted from anatomical images. We
      present a novel method that uses a dimensionality reduction from thousands down
      to the range of tens of parameters to successfully represent an individual 4
      shell Boundary Element Method (BEM) head model, which can successively be fitted
      to any kind of data from an individual head (e.g. headshape, impedances) and then
      used for individual head model creation. The results show, that around 15 - 20
      components can lead to satisfactory results.

PMID- 29060702
TI  - GPU-based volume reconstruction for freehand 3D ultrasound imaging.
AB  - Volume reconstruction plays an important role in improving image quality for
      freehand three-dimensional (3D) ultrasound imaging. The kernel regression
      provides an effective method for volume reconstruction in 3D ultrasound imaging,
      but it requires heavily computational time-cost. In this paper, a programmable
      graphic-processor-unit-(GPU) based fast kernel regression method is proposed for
      freehand 3D ultrasound volume reconstruction. The most significant aspect of our
      method is the adopting of powerful data-parallel computing capability of GPU to
      improve the overall efficiency. To produce higher image quality, the results of
      the kernel regression with various parameter settings is deeply investigated
      under the help of the fast implementation of the algorithm. Experimental results
      demonstrate that the computational performance of the proposed GPU-based method
      can be over 200 times faster than that on CPU. Better image quality for speckle
      reduction and details preservation can be obtained with the parameter setting of
      kernel window size of 5*5*5 and kernel bandwidth of 1.0.

PMID- 29060703
TI  - BrainWatch software for interactive exploration of brain scans in 3D virtual
      reality systems.
AB  - The ability to view medical images as 3D objects, which can be explored
      interactively, has now become possible due to the advent of rapidly emerging
      virtual reality (VR) technologies. In the past, VR has been used as an
      educational tool for learning anatomy, a visualization tool for assisting
      surgery, and a therapeutic tool for rehabilitating patients with motor disorders.
      However, these older systems were either expensive to build or difficult to
      acquire and use. Exploiting the arrival of new consumer devices such as the
      Oculus Rift that are now affordable, we have developed a software application
      called BrainWatch for VR ready computers to enable 3D visualization and
      interactive exploration of DICOM data sets focusing on PET and MRI brain scans.
      BrainWatch software provides a unique set of 3 approaches for interacting with
      the virtual object which we have named the observatory scenario with an external
      camera, the planetarium scenario with an internal camera, and the voyager
      scenario with a mobile camera. A live interactive demo of BrainWatch VR with the
      Oculus Rift CV1 will be available for conference attendees to experience at EMBC
      2017.

PMID- 29060704
TI  - Image recognition of triangular tissue of an organ pulled by forceps in surgical
      working area for laparoscope robot.
AB  - An image processing method using selected corner points and ridge lines to
      recognize triangular tissue of an organ pulled by forceps in a laparoscopic view
      has been developed. The proposed method could be used for semi-automatic control
      of a laparoscope robot. It makes use of a masking process based on the
      recognition of the forceps and clots, detection of corner points for a Delaunay
      diagram, detection of ridge lines oriented in the same direction, and recognition
      of the triangular working area. Triangles recognized in laparoscopic surgical
      videos using this method were similar to the correct triangles made by an
      endoscopic specialist.

PMID- 29060705
TI  - Cardiac safety profile for Random Complex Waveforms.
AB  - INTRODUCTION: A rigorous method for assessing the Ventricular Fibrillation (VF)
      risk of a Random Complex Waveform (RCW) has not been previously available. Real
      life hazardous events motivated us to develop such method. An RCW is observable
      and recordable. It consists of multiple different components randomly added one
      to the other. Assessment for VF risk exists for non-random waveforms,
      particularly VF thresholds for 50/60 Hz alternating currents, but not for RCWs.
      METHODS: We developed a method which considers exposure to a segment of an RCW.
      It transforms complex segment exposure to values which can be compared with AC
      root-mean-square (rms) magnitude/duration curves, for determination of VF risk.
      Human contact could occur for any given time duration within the segment. The
      current of most risk is the greatest found for all possible instances of that
      duration. This is termed the "Probable Current" (PC) for that duration. All
      possible exposure durations in the waveform segment are considered, giving a set
      of PCs, thus allowing the plotting of a PC curve. The PC set is compared with a
      criterion for VF risk, termed the Justified Current (JC) curve. RESULTS: The
      theory is presented. Demonstrations and examples are given. Code is shown for
      generating the PC curve. CONCLUSION: VF risk can be found for an RCW using the
      rigorous algorithm presented. SIGNIFICANCE: The VF for RCWs has not been
      considered previously. A rigorous statement of a method for VF risk assessment
      allows extension from regular waveforms to RCWs.

PMID- 29060706
TI  - Development of respiratory function monitor for neonates.
AB  - Approximately, 10 million babies do not breathe immediately at birth and some of
      them require positive pressure ventilation. However, inappropriate and excessive
      tidal volume delivery could lead to lung injury in neonatal patients. We
      developed a respiratory function monitor which can monitor mask leak, expiratory
      tidal volume, respiratory rate, peak inspiratory pressure, and end-tidal CO2 on a
      real-time basis. A neonatal flow sensor was specially designed and was integrated
      with a small mainstream capnometer, cap-ONE. Usability was enhanced by using a
      tablet for the display of the monitored parameters. The basic performance
      evaluation using a neonatal training test lung shows that the respiratory
      function monitor effectively detects mask leak. The system may help healthcare
      providers to efficiently support neonatal patients start breathing.

PMID- 29060707
TI  - Transmission delay performance in telemedicine: A case study.
AB  - Given the prevalence of chronic health conditions, such as diabetes, obesity,
      epilepsy, and cardiovascular diseases, telemedicine technologies are increasingly
      adopted to help patients better manage their care and treat these diseases at
      home. These emerging telemedicine systems have been deployed and tested in a
      number of different health programs and hospitals. However, due to the lack of
      dedicated and reliable networking infrastructure, achieving real-time data
      collection is very challenging task. In this paper, we conduct a comprehensive
      analysis on the delay issues presented during the use of a store and forward
      telemonitoring system for congestive heart failure patients in urban
      Philadelphia. Results from this analysis reveal that 10.3% of the patient
      measurements experience delays of longer than 12 hours. Delays of up to several
      days occurred in 15.38% these patients who went on to be hospitalized. These
      delay issues exposed from urban scale real systems have direct impact on the
      quality of remote health care, causing late diagnosis and intervention especially
      when patients are experiencing acute exacerbations. Our investigation results
      essentially call for regulations on telemedicine systems with an emphasis on
      their temporal constraints.

PMID- 29060708
TI  - A novel platform for distributed and remote real-time monitoring of animal model
      behavior in a bioterium.
AB  - Animal models are an important resource in life sciences research; however, many
      of the procedures involving vivo models are complex and time consuming. A common
      problem while conducting experiments is observing the behavior of the models
      throughout their stay in the bioterium. Ideally, behavioral assessment should be
      frequent and rigorous, as a way of more accurately characterizing the animal
      model. However, to date, few suitable automated solutions can be found within the
      state-of-the-art. In this paper, we propose an autonomous platform for
      distributed behavioral data acquisition from individual animal habitats in
      bioteriums, with remote and online access to the data. This approach allows real
      time observation of the status of the habitats, and retrieval of the logged data
      for post-processing. The work focuses on the use case of motion, temperature and
      water intake monitoring in small rodents, although the platform was designed to
      be general-purpose and extensible to other types of habitats and sensing
      configurations.

PMID- 29060709
TI  - iQuantTM Analyser: A rapid quantitative immunoassay reader.
AB  - Lateral flow immunoassays (LFIA) used in rapid quantitative point of care testing
      require an accurate, reliable and easy to operate instrument to read the LFIA kit
      and calculate the quantitative result value. We present iQuant(r) Analyser, an
      immunoassay reader designed for reading the Quanti(r) range of LFIA test kits for
      key markers such as HbA1C, Vitamin D, TSH etc. The instrument utilizes a laser
      based confocal optics system to capture the test and control lines from the LFIA
      kit, digitizes the fluorescent signal with high spatiotemporal resolution,
      computes necessary peak area ratios, applies calibration curves and declares the
      final result in an automated manner with minimal operator input. The instrument
      uses kit specific calibration information embedded on each LFIA test kit, to
      compute the final clinical parameter without using any external calibration chip.
      An intuitive icon based interface enables easy operation with minimal key
      presses, suited for point of care applications. The technology is designed in a
      modular manner to enable the instrument to perform tests on various parameters
      such as HbA1C, TSH, and Vitamin D etc without any hardware changes, using test
      specific LFIA kits. The functional performance of the iQuant Analyser was
      verified over the range of expected area ratio values with standard reference
      cartridges that provided stable fluorescent lines. Repeatability of the
      instrument was found to be excellent with coefficient of variation (CoV) of area
      ratios found to be less than 1%. The inter-instrument reproducibility was also
      found to be good with CoV less than 4 %. Tests using blood samples with Quanti
      LFIA kits verified the accuracy of HbA1C results to be acceptable as per
      international standards with errors <; 4 %. The iQuant Analyser is a portable,
      easy to use rapid quantitative immunoassay reader best suited for point of care
      applications.

PMID- 29060710
TI  - Snore sound recognition: On wavelets and classifiers from deep nets to kernels.
AB  - In this paper, we present a comprehensive comparison of wavelet features for the
      classification of snore sounds. Wavelet features have proven to be efficient in
      our previous work; however, the benefits of wavelet transform energy (WTE) and
      wavelet packet transform energy (WPTE) features were not clearly established. In
      this study, we firstly present our updated snore sounds database, expanded from
      24 patients (collected by one medical centre) to 40 patients (collected by three
      medical centres). We then study the effects of varying frame sizes and overlaps
      for extraction of the wavelet low-level descriptors, the effect of which have yet
      to be fully established. We also compare the performance of the WTE and WPTE
      features when fed into multiple classifiers, namely, Support Vector Machines
      (SVM), K-Nearest Neighbours, Linear Discriminant Analysis, Random Forests,
      Extreme Learning Machines, Kernel Extreme Learning Machines, Multilayer
      Perceptron, and Deep Neural Networks. Key results presented indicate that, when
      fed into a SVM, WTE outperforms WPTE (one-tailed z-test, p<;0.002). Further, WPTE
      can achieve a significant improvement when trained by a k-nearest neighbours
      classifier (one-tailed z-test, p <; 0.001).

PMID- 29060711
TI  - A Bayesian neural network approach to compare the spectral information from nasal
      pressure and thermistor airflow in the automatic sleep apnea severity estimation.
AB  - In the sleep apnea-hypopnea syndrome (SAHS) context, airflow signal plays a key
      role for the simplification of the diagnostic process. It is measured during the
      standard diagnostic test by the acquisition of two simultaneous sensors: a nasal
      prong pressure (NPP) and a thermistor (TH). The current study focuses on the
      comparison of their spectral content to help in the automatic SAHS-severity
      estimation. The spectral analysis of 315 NPP and corresponding TH recordings is
      firstly proposed to characterize the conventional band of interest for SAHS
      (0.025-0.050 Hz.). A magnitude squared coherence analysis is also conducted to
      quantify possible differences in the frequency components of airflow from both
      sensors. Then, a feature selection stage is implemented to assess the relevance
      and redundancy of the information extracted from the spectrum of NPP and TH
      airflow. Finally, a multiclass Bayesian multi-layer perceptron (BY-MLP) was used
      to perform an automatic estimation of SAHS severity (no-SAHS, mild, moderate, and
      severe), by the use of the selected spectral features from: airflow NPP alone,
      airflow TH alone, and both sensors jointly. The highest diagnostic performance
      was reached by BY-MLP only trained with NPP spectral features, reaching Cohen's
      kappa = 0.498 in the overall four-class classification task. It also achieved
      91.3%, 84.9%, and 83.3% of accuracy in the binary evaluation of the 3 apnea
      hypopnea index cut-offs (5, 15, and 30 events/hour) that define the four SAHS
      degrees. Our results suggest that TH sensor might be not necessary for SAHS
      severity estimation if an automatic comprehensive characterization approach is
      adopted to simplify the diagnostic process.

PMID- 29060712
TI  - Estimation of a priori probabilities of sleep stages: A cycle-based approach.
AB  - This paper presents a model for the estimation of a priori probabilities of sleep
      epoch classes based on the epoch location in a sleep cycle. These probabilities
      are used as additional features for sleep stage classification based on the
      analysis of respiratory effort. The model was validated with data of 685 subjects
      selected from the Sleep Heart Health Study dataset. The model improves a base
      algorithm by 8 percent points and demonstrates Cohen's kappa of 0.56 +/- 0.12.
      Our results will contribute to the development of screening tools for unobtrusive
      sleep structure estimation.

PMID- 29060713
TI  - Comparing two insomnia detection models of clinical diagnosis techniques.
AB  - Sleep disorders are becoming increasingly prevalent in society. However most of
      the burgeoning research on automated sleep analysis has been in the realm of
      sleep stage classification with limited focus on accurately diagnosing these
      disorders. In this paper, we explore two different models to discriminate between
      control and insomnia patients using support vector machine (SVM) classifiers. We
      validated the models using data collected from 124 participants, 70 control and
      54 with insomnia. The first model uses 57 features derived from two channels of
      EEG data and achieved an accuracy of 81%. The second model uses 15 features from
      each participant's hypnogram and achieved an accuracy of 74%. The impetus behind
      using these two models is to follow the clinician's diagnostic decision-making
      process where both the EEG signals and the hypnograms are used. These results
      demonstrate that there is potential for further experimentation and improvement
      of the predictive capability of the models to help in diagnosing sleep disorders
      like insomnia.

PMID- 29060714
TI  - Usefulness of discrete wavelet transform in the analysis of oximetry signals to
      assist in childhood sleep apnea-hypopnea syndrome diagnosis.
AB  - Sleep apnea hypopnea syndrome (SAHS) is a highly prevalent respiratory disorder
      that may cause many negative consequences for the health and development of
      children. The gold standard for diagnosis is the overnight polysomnography (PSG),
      which is a high cost, complex, intrusive, and time-demanding technique. To
      improve the early detection of pediatric SAHS, we propose an automated analysis
      of the SpO2 signal from nocturnal oximetry. A database composed of 298 SpO2
      recordings from children ranging from 0 to 13 years old was used for this
      purpose. Due to the abrupt changes caused by respiratory events in the SpO2
      signal, our goal was to evaluate the diagnostic ability of this by means of the
      discrete wavelet transform (DWT). To achieve this objective, we conducted a
      signal processing approach divided into two main stages: (i) feature extraction,
      where features from the DWT detail coefficients were computed, and (ii) feature
      classification, where a logistic regression (LR) model was used to classify
      children into SAHS negative or SAHS positive. Our results showed that respiratory
      events introduced more variability in two detail levels of the DWT from SpO2:
      0.024-0.049 Hz and 0.012-0.024 Hz. Moreover, the LR classifier achieved an 81.9%
      accuracy (79.1% sensitivity and 84.1% specificity) in an independent test set for
      a clinical cutoff point of 5 events/h, as derived from PSG. These results suggest
      that DWT analysis may be a useful tool to analyze SpO2 recordings in the context
      of childhood SAHS.

PMID- 29060715
TI  - Detecting obstructive sleep apnea in children by self-affine visualization of
      oximetry.
AB  - Obstructive sleep apnea (OSA), characterized by cessations of breathing during
      sleep due to upper airway collapse, can affect the healthy growth and development
      of children. The gold standard for OSA diagnosis, polysomnography(PSG), is
      expensive and resource intensive, resulting in long waiting lists to perform a
      PSG. Previously, we investigated the time-frequency analysis of blood oxygen
      saturation (SpO2) to screen for OSA. We used overnight pulse oximetry from 146
      children, collected using a smartphone-based pulse oximeter (Phone Oximeter),
      simultaneously with standard PSG. Sleep technicians manually scored PSG and
      provided the average of apnea/hypoapnea events per hour (AHI). In this study, we
      proposed an alternative method for analyzing SpO2, in which a set of contracting
      transformations form a self-affine set with a 2D attractor, previously developed
      for qualitative visualization of the photoplethysmogram and electroencephalogram.
      We applied this technique to the overnight SpO2 signal from individual patients
      and extracted features based on the distribution of points (radius and angle) in
      the visualization. The cloud of points in children without OSA (NonOSA) was more
      confined than in children with OSA, which was reflected by more empty pixels
      (radius and angles). The maximum value, skewness and standard deviation of the
      distribution of points located at different radius and angles were significantly
      (Bonferroni corrected) higher in NonOSA compared to OSA children. To detect OSA
      defined at different levels (AHI>=5, AHI>=10 and AHI>=15), three multivariate
      logistic regression models were implemented using a stepwise feature selection
      and internally validated through bootstrapping. The models (AHI>=5, AHI>=10,
      AHI>=15), consisting of 3, 4 and 1 features respectively, provided a bootstrap
      corrected AUC of 73%, 81%, 73%. Thus, applying this visualization to nocturnal
      SpO2 could yield both visual and quantitative information that might be useful
      for screening children for OSA.

PMID- 29060716
TI  - Multiscale properties of instantaneous parasympathetic activity in severe
      congestive heart failure: A survivor vs non-survivor study.
AB  - Multifractal analysis of cardiovascular variability series is an effective tool
      for the characterization of pathological states associated with congestive heart
      failure (CHF). Consequently, variations of heartbeat scaling properties have been
      associated with the dynamical balancing of nonlinear sympathetic/vagal activity.
      Nevertheless, whether vagal dynamics has multifractal properties yet alone is
      currently unknown. In this study, we answer this question by conducting
      multifractal analysis through wavelet leader-based multiscale representations of
      instantaneous series of vagal activity as estimated from inhomogeneous point
      process models. Experimental tests were performed on data gathered from 57 CHF
      patients, aiming to investigate the automatic recognition accuracy in predicting
      survivor and non-survivor patients after a 4 years follow up. Results clearly
      indicate that, on both CHF groups, the instantaneous vagal activity displays
      power-law scaling for a large range of scales, from ? 0.5s to ? 100s. Using
      standard SVM algorithms, this information also allows for a prediction of
      mortality at a single-subject level with an accuracy of 72.72%.

PMID- 29060717
TI  - Validation of instantaneous bispectral high-frequency power of heartbeat dynamics
      as a marker of cardiac vagal activity.
AB  - Nonlinear analysis has been advocated as a very powerful methodological framework
      to study physiological signals, particularly when applied to heartbeat dynamics.
      To this extent, estimation of high-frequency (0.15-0.40 Hz) power from bispectra
      of cardiovascular variability series has been engaged as a marker of nonlinear
      vagal activity. Nevertheless, a proper validation of this specific measure has
      not been yet performed. In this study, we estimate instantaneous, nonlinear
      bispectral indices during postural changes under sympathetic and parasympathetic
      nervous system blockade. The analysis was performed on data from 14 healthy
      subjects undergoing a control supine-to-upright routine where they were
      selectively administered either atropine or propanolol. Instantaneous bispectra
      were obtained through Laguerre-transformed, linear and nonlinear kernels of a
      Wiener-Volterra model applied to heartbeat dynamics, embedded into a recently
      proposed inhomogeneous point-process framework. Results demonstrate that the
      integration of bispectra accounting for nonlinear cardiovascular control dynamics
      within the high-frequency band provides potentially reliable markers of vagal
      activity.

PMID- 29060718
TI  - Spatially regularized multifractal analysis for fMRI data.
AB  - Scale-free dynamics is nowadays a massively used paradigm to model infraslow
      macroscopic brain activity. Multifractal analysis is becoming the standard tool
      to characterize scale-free dynamics. It is commonly used on various modalities of
      neuroimaging data to evaluate whether arrhythmic fluctuations in ongoing or
      evoked brain activity are related to pathologies (Alzheimer, epilepsy) or task
      performance. The success of multifractal analysis in neurosciences remains
      however so far contrasted: While it lead to relevant findings on M/EEG data, less
      clear impact was shown when applied to fMRI data. This is mostly due to their
      poor time resolution and very short duration as well as to the fact that analysis
      remains performed voxelwise. To take advantage of the large amount of voxels
      recorded jointly in fMRI, the present contribution proposes the use of a recently
      introduced Bayesian formalism for multifractal analysis, that regularizes the
      estimation of the multifractality parameter of a given voxel using information
      from neighbor voxels. The benefits of this regularized multifractal analysis are
      illustrated by comparison against classical multifractal analysis on fMRI data
      collected on one subject, at rest and during a working memory task: Though not
      yet statistically significant, increased multifractality is observed in task
      negative and task-positive networks, respectively.

PMID- 29060719
TI  - Development and assessment of a novel ankle rehabilitation system for stroke
      survivors.
AB  - Spasticity after stroke is a common occurrence and requires treatment with
      rehabilitative regimens (e.g., stretching exercise). Unfortunately, many
      challenges (e.g., cost, limited availability of physical therapists, limited
      access to clinical facilities, etc.) can restrict participation in these
      rehabilitation regimens. Assistive technologies using robotic systems have been
      developed to provide an alternative to assist with rehabilitative exercises.
      However, existing assistive technologies are rarely available in clinical
      settings due to technical limitations (e.g., size, weight, complexity, etc.).
      This paper describes the development of a novel ankle rehabilitation system,
      called Motorized Ankle Stretcher (MAS). A proof-of-concept experiment was
      conducted to assess the effects of ankle stretching exercises with the MAS in a
      laboratory setting. Six stroke survivors participated in the proof-of-concept
      experiment. The participants' ankle range of motion (ROM) and walking performance
      (i.e., walking speed, step length, and cadence) were evaluated before and after a
      small number of the ankle stretching exercises using the MAS (i.e., 20 trials
      total) in a single training session. The results show that the ankle ROM was
      significantly increased after the exercises across all participants. However, no
      significant differences in walking speed, step length, and cadence were observed
      between pre- and post-exercises. Our investigation is a first attempt at
      developing a relatively small size, weight, and easy-to-use ankle rehabilitation
      system for stroke survivors.

PMID- 29060720
TI  - A new fall-inducing technology platform: Development and assessment of a
      programmable split-belt treadmill.
AB  - Typical technologies for fall reduction/prevention training incorporate
      mechanical obstacles or cables/pulleys to induce trip or slip perturbations. This
      paper proposes a technology platform that uses a split-belt treadmill equipped
      with one force plate underneath each belt and a real-time gait phase detection
      algorithm. A proof-of-concept study validates the method for inducing trip
      perturbations in healthy young adults (n=10) by using kinematic measures from a
      full body motion capture system to characterize the effects of the perturbations.
      Preliminary results show that the proposed method successfully induces a trip and
      its congruent postural responses. The major findings have implications for
      designing intervention programs to reduce or prevent falls by individuals with a
      high risk of falls.

PMID- 29060721
TI  - Smart mobility solution with multiple input Output interface.
AB  - Smart wheelchairs are commonly used to provide solution for mobility impairment.
      However their usage is limited primarily due to high cost owing from sensors
      required for giving input, lack of adaptability for different categories of input
      and limited functionality. In this paper we propose a smart mobility solution
      using smartphone with inbuilt sensors (accelerometer, camera and speaker) as an
      input interface. An Emotiv EPOC+ is also used for motor imagery based input
      control synced with facial expressions in cases of extreme disability. Apart from
      traction, additional functions like home security and automation are provided
      using Internet of Things (IoT) and web interfaces. Although preliminary, our
      results suggest that this system can be used as an integrated and efficient
      solution for people suffering from mobility impairment. The results also indicate
      a decent accuracy is obtained for the overall system.

PMID- 29060722
TI  - Simple and low-cost polymer lens fabrication using a pressure-driven micro
      chamber.
AB  - In this paper, a low-cost lens fabrication method using a micro chamber produced
      by a three-dimensional (3-D) printer is presented. The shape of
      polydimethylsiloxane (PDMS) membrane was controlled by adjusting the pressure
      inside the chamber. On top of the shaped membrane, an ultraviolet-curable resin
      was poured. Depending on the pressure inside the chamber and the shape of the
      chamber lid, three types of lenses could be made: a bi-convex lens, a plano
      convex lens, and a concave lens. This method can reduce the cost of making pilot
      or evaluation devices in healthcare service.

PMID- 29060723
TI  - Proposal of custom made wrist orthoses based on 3D modelling and 3D printing.
AB  - Accessibility to three-dimensional (3D) technologies, such as 3D scanning systems
      and additive manufacturing (like 3D printers), allows a variety of 3D
      applications. For medical applications in particular, these modalities are
      gaining a lot of attention enabling several opportunities for healthcare
      applications. The literature brings several cases applying both technologies, but
      none of them focus on the spreading of how this technology could benefit the
      health segment. This paper proposes a new methodology, which employs both 3D
      modelling and 3D printing for building orthoses, which could better fit the
      demands of different patients. Additionally, there is an opportunity for sharing
      expertise, as it represents a trendy in terms of the maker-movement. Therefore,
      as a result of the proposed approach, we present a case study based on a
      volunteer who needs an immobilization orthosis, which was built for
      exemplification of the whole process. This proposal also employs freely available
      3D models and software, having a strong social impact. As a result, it enables
      the implementation and effective usability for a variety of built to fit
      solutions, hitching useful and smarter technologies for the healthcare sector.

PMID- 29060724
TI  - A flexible method for the automated offline-detection of artifacts in multi
      channel electroencephalogram recordings.
AB  - Electroencephalogram (EEG) signal quality is often compromised by artifacts that
      corrupt quantitative EEG measurements used in clinical applications and EEG
      related studies. Techniques such as filtering, regression analysis and blind
      source separation are often used to remove these artifacts. However, these
      preprocessing steps do not allow for complete artifact correction. We propose a
      method for the automated offline-detection of remaining artifacts after
      preprocessing in multi-channel EEG recordings. In contrast to existing methods it
      requires neither adaptive parameters varying between recordings nor a topography
      template. It is suited for short EEG segments and is flexible with regard to
      target applications. The algorithm was developed and tested on 60 clinical EEG
      samples of 20 seconds each that were recorded both in resting state and during
      cognitive activation to gain a realistic artifact set. Five EEG features were
      used to quantify temporal and spatial signal variations. Two distance measures
      for the single-channel and multi-channel variations of these features were
      defined. The global thresholds were determined by three-fold cross-validation and
      Youden's J statistic in conjunction with receiver operating characteristics (ROC
      curves). We observed high sensitivity of 95.5%+/-4.8 and specificity of 88.8%+/
      2.1. The method has thus shown great potential and is promising as a possible
      tool for both EEG-based clinical applications and EEG-related research.

PMID- 29060725
TI  - Elucidating age-specific patterns from background electroencephalogram pediatric
      datasets via PARAFAC.
AB  - Brain-computer interfaces (BCI) have the potential to provide non-muscular
      rehabilitation options for children. However, progressive changes in
      electrophysiology throughout development may pose a potential barrier in the
      translation of BCI rehabilitation schemes to children. Tensors and multiway
      analysis could provide tools which help characterize subtle developmental changes
      in electroencephalogram (EEG) profiles of children, thus supporting translation
      of BCI paradigms. Spatial, spectral and subject information of age-matched
      pediatric subjects in two EEG datasets were used to form 3-dimensional tensors
      for use in parallel factor analysis (PARAFAC) and direct projection comparison.
      Within dataset cross-validation results indicate PARAFAC can extract age
      sensitive factors which accurately predict subject age in 90% of cases. Cross
      dataset validation revealed extracted age-dependent factors correctly identified
      age in 3 of 4 test subjects. These findings demonstrate that tensor analysis can
      be applied to characterize the age-specific subtleties in EEG, which provide a
      means for tracking developmental changes in pediatric rehabilitation BCIs.

PMID- 29060726
TI  - Speech features for telemonitoring of Parkinson's disease symptoms.
AB  - The aim of this paper is tracking Parkinson's disease (PD) progression based on
      its symptoms on vocal system using Unified Parkinsons Disease Rating Scale
      (UPDRS). We utilize a standard speech signal feature set, which contains 6373
      static features as functionals of low-level descriptor (LLD) contours, and select
      the most informative ones using the maximal relevance and minimal redundancy
      based on correlations (mRMRC) criteria. Then, we evaluate performance of Gaussian
      mixture regression (GMR) and support vector regression (SVR) on estimating the
      third subscale of UPDRS, i.e., UPDRS: motor subscale (UPDRS-III). Among the most
      informative features, a list of features are selected after redundancy reduction.
      The selected features depict that LLDs providing information about spectrum
      flatness, spectral distribution of energy, and hoarseness of voice are the most
      important ones for estimating UPDRS-III. Moreover, the most informative
      statistical functions are related to range, maximum, minimum and standard
      deviation of LLDs, which is an evidence of the muscle weakness due to the PD.
      Furthermore, GMR outperforms SVR on compact feature sets while the performance of
      SVR improves by increasing number of features.

PMID- 29060727
TI  - "You sound ill, take the day off": Automatic recognition of speech affected by
      upper respiratory tract infection.
AB  - A combination of passive, non-invasive and nonintrusive smart monitoring
      technologies is currently transforming healthcare. These technologies will soon
      be able to provide immediate health related feedback for a range of illnesses and
      conditions. Such tools would be game changing for serious public health concerns,
      such as seasonal cold and flu, for which early diagnosis and social isolation
      play a key role in reducing the spread. In this regard, this paper explores, for
      the first times, the automated classification of individuals with Upper
      Respiratory Tract Infections (URTI) using recorded speech samples. Key results
      presented indicate that our classifiers can achieve similar results to those seen
      in related health-based detection tasks indicating the promise of using
      computational paralinguistic analysis for the detection of URTI related
      illnesses.

PMID- 29060728
TI  - Linear-Sigmoidal modelling of accelerometer features and Tinetti score for
      automatic fall risk assessment.
AB  - Falling in elderly is a worldwide major problem and it can lead to severe
      injuries or death. Despite the effort made to ensure home environments safe and
      foster healthy lifestyles, it is still necessary to provide methodologies that
      can be used at home for detect risk factors associated with falls. In this study,
      we proposed a new simple non-linear model, i.e., Linear-Sigmoidal model (LS),
      easy to fit and simple to interpret, used to model accelerometer features and
      outcome of the clinical scale Tinetti (clinical scale for fall risk prediction).
      Also, subjects with a score <= 18 were considered as high risk of falling. One
      hundred-twelve subjects underwent to a Tinetti test while wearing a 3D axis
      accelerometer at the chest, and the Tinetti score used as gold standard. Ninety
      subjects were used as training set and twenty-two ones were employed to test the
      model. The same sets were used to assess the performance of the standard linear
      regression (LR). Seven accelerometer features and the body mass index were used
      in the model regression. LS resulted better than LR in terms of model agreement
      (R2: 0.76 vs 0.72) and classification accuracy (0.91 vs 0.86) on the test set.

PMID- 29060729
TI  - Convolutional neural network architecture and input volume matrix design for ERP
      classifications in a tactile P300-based Brain-Computer Interface.
AB  - In the presented study we conduct the off-line ERP classification using the
      convolutional neural network (CNN) classifier for somatosensory ERP intervals
      acquired in the full- body tactile P300-based Brain-Computer Interface paradigm
      (fbBCI). The main objective of the study is to enhance fbBCI stimulus pattern
      classification accuracies by applying the CNN classifier. A 60 * 60 squared input
      volume transformed by one-dimensional somatosensory ERP intervals in each
      electrode channel is input to the convolutional architecture for a filter
      training. The flattened activation maps are evaluated by a multilayer perceptron
      with one-hidden-layer in order to calculate classification accuracy results. The
      proposed method reveals that the CNN classifier model can achieve a non-personal-
      training ERP classification with the fbBCI paradigm, scoring 100 % classification
      accuracy results for all the participated ten users.

PMID- 29060730
TI  - Estimation of respiratory rate from thermal videos of preterm infants.
AB  - Studies have demonstrated that respiratory rate (RR) is a good predictor of the
      patient condition as well as an early marker of patient deterioration and
      physiological distress. However, it is also referred as "the neglected vital
      parameter". This is mainly due to shortcoming of current monitoring techniques.
      Moreover, in preterm infants, the removal of adhesive electrodes cause epidermal
      stripping, skin disruption, and with it pain. This paper proposes a new algorithm
      for estimation of RR in thermal videos of moderate preterm infants. It uses the
      temperature modulation around the nostrils over the respiratory cycle to extract
      this vital parameter. To compensate movement artifacts the approach incorporates
      a tracking algorithm. In addition, a new reliable and accurate algorithm for
      robust estimation of local (breath-to-breath) intervals was included. To evaluate
      the performance of this approach, thermal recordings of four moderate preterm
      infants were acquired. Results were compared with RR derived from body surface
      electrocardiography. The results showed an excellent agreement between thermal
      imaging and gold standard. On average, the relative error between both monitoring
      techniques was 3.42%. In summary, infrared thermography may be a clinically
      relevant alternative to conventional sensors, due to its high thermal resolution
      and outstanding characteristics.

PMID- 29060731
TI  - Automated segmentation of regions of interest from thermal images of hands.
AB  - Thermal imaging can provide an image of the surface temperature of an object in a
      non-contact and noninvasive manner, making it particularly appealing for use in
      medical applications. In applications where it is desirable to extract
      temperature data from anatomical regions of interest (ROIs) in a standardised and
      consistent manner, the use of automated segmentation and analysis techniques can
      provide a faster, more reliable and more consistent approach than manual
      segmentation of these ROIs. In this paper we present an algorithm which
      automatically extracts temperature data from eight ROIs in thermal images of the
      volar aspect of human hands. The algorithm first identifies the hand from the
      background in the thermal image and then identifies pixels which make up the
      fingers and the palm. Finally, eight ROIs are extracted from the identified
      regions. The methods proposed in this work can also be extended for the
      processing of similar visual images.

PMID- 29060732
TI  - Automatic analysis of the aggressive behavior of laboratory animals using thermal
      video processing.
AB  - The bite detection is very important but difficult element of the social
      interaction analysis. Standard observation methods like human observer or a
      camcorder of visible light frequencies fail in this case. However, it is possible
      to discern cooler spots on the rodent's body that appear after body contact with
      another individual, and vanish after short time. These spots are assumed to be a
      saliva trace left on fur after bite. In this paper we have described a result of
      saliva trace detection by the most popular corner detectors. The analysis of
      traces and their parameters is also presented. The dynamic characteristic of the
      temperature change of the saliva trace enables the automatic discrimination of
      the related characteristic point from other corner points. This can be very
      useful for the automatic analysis of social behavior of animals in many
      pharmacological studies.

PMID- 29060733
TI  - Development of a "Thermal-Associated Pain Index" score using infrared
      thermography for objective pain assessment.
AB  - Without any doubt, research in biomedical engineering and anesthesiology achieved
      diverse ground-breaking successes for the sake of patient safety and for
      optimization of medical treatment in the last decades. Particularly anesthesia
      has become increasingly comfortable and safer due to new monitoring devices and
      further techniques. However, assessment of pain still relies on self-reporting of
      the patient using a Numeric Rating Scale ranging from 0 to 10. Obviously, this
      method suffers from severe restraints when unconscious, anesthetized or
      uncooperative subjects or children are involved as patients. Furthermore, no
      continuous monitoring is available so that features like alerting telemetry are
      lacking. Several scientific groups and companies searched intensively for
      procedures to measure pain objectively. Skin conductance, heart rate variability
      and peripheral perfusion, among others, were used to develop new algorithms and
      devices. Up to date, none of these devices succeeded to enter in clinical
      routine. In this project, we used infrared thermography (IRT) to analyze facial
      expressions and further thermal-associated phenomena that are visible in recorded
      IRT sequences such as lacrimation and perspiration. By means of clinical
      observations, a number of IRT features were predefined that were expected to
      correlate with pain. The combination of those features led to the so-called
      "Thermal-Associated Pain Intensity" (TAPI) after normalization and
      transformation. The TAPI correlates significantly with the NRS and achieves a
      sensitivity of above 0.75 to detect pain.

PMID- 29060734
TI  - Comparison of motion-based analysis to thermal-based analysis of thermal video in
      the extraction of respiration patterns.
AB  - Non-contact methods of extracting vital signals has become a popular area of
      research. This is likely due to the world's aging population and the increased
      need for long term and remote monitoring. This paper examines and compares the
      potential for one modality to capture a vital sign, specifically respiration, in
      the presence of signal abnormalities. This paper compares temperature based
      methods to motion-based methods of extracting respiration rate from thermal video
      of a subject performing computationally difficult respiration tests. The thermal
      video was subjected to segmentation-based image processing and region tracking to
      encompass temperature changes over time. All methods were successful in
      identifying regular breathing and the absence of breathing, but differed in
      performance identifying hyperventilation and obstructive sleep apnea simulated
      breathing. The temperature-based method better depicted airflow volume, while the
      motion-based method better depicted absence of breath and chest movement; neither
      signal on its own was able to accurately depict OSA breathing. These results
      suggest that the fusion of information from different physical phenomenon (i.e.
      motion and temperature) is important here in detecting abnormal breathing
      patterns, but also in the detection of all vital signals, adding algorithmic
      robustness in the presence of signal abnormalities.

PMID- 29060735
TI  - A sub-nJ CMOS ECG classifier for wireless smart sensor.
AB  - Body area sensor networks hold the promise of more efficient and cheaper medical
      care services through the constant monitoring of physiological markers such as
      heart beats. Continuously transmitting the electrocardiogram (ECG) signal
      requires most of the wireless ECG sensor energy budget. This paper presents the
      analog implantation of a classifier for ECG signals that can be embedded onto a
      sensor. The classifier is a sparse neural associative memory. It is implemented
      using the ST 65 nm CMOS technology and requires only 234 pJ per classification
      while achieving a 93.6% classification accuracy. The energy requirement is 6
      orders of magnitude lower than a digital accelerator that performs a similar
      task. The lifespan of the resulting sensor is 191 times as large as that of a
      sensor sending all the data.

PMID- 29060736
TI  - A low power, low noise Programmable Analog Front End (PAFE) for biopotential
      measurements.
AB  - A low power Programmable Analog Front End (PAFE) for biopotential measurements is
      presented in this paper. The PAFE circuit processes electrocardiogram (ECG),
      electromyography (EMG) and electroencephalogram (EEG) signals with higher
      accuracy. It consists mainly of improved transconductance programmable gain
      instrumentational amplifier (PGIA), programmable high pass filter (PHPF), and
      second order low pass filter (SLPF). A 15-bit programmable 5-stage successive
      approximation analog-to-digital converter (SAR-ADC) is implemented for improving
      the performance, whose power consumption is reduced due to multiple stages and by
      OTA/Comparator sharing technique between the stages. The power consumption is
      further reduced by operating the analog portion of PAFE on 0.5V supply voltage
      and digital portion on 0.3V supply voltage generated internally through a voltage
      regulator. The proposed low power PAFE has been fabricated in 180nm standard CMOS
      process. The performance parameters of PAFE in 15-bit mode are found to be, gain
      of 31-70 dB, input referred noise of 1.15 MUVrms, CMRR of 110 dB, PSRR of 104 dB,
      and signal-to-noise distortion ratio (SNDR) of 83.5dB. The power consumption of
      the design is 1.1 MUW @ 0.5 V supply voltage and it occupies a core silicon area
      of 1.2 mm2.

PMID- 29060737
TI  - Improving efficiency of DC/DC booster converters used in electrical stimulators.
AB  - Power efficiency is critical for electrical stimulators. Battery life of wearable
      stimulators and wireless power transmission in implanted systems are common
      limiting factors. Boost DC/DC converters are typically needed to increase the
      supply voltage of the output stage. Traditionally, boost DC/DC converters are
      used with fast control to regulate the supply voltage of the output. However,
      since stimulators are acting as current sources, such voltage regulation is not
      needed. Banking on this, this paper presents a DC/DC conversion strategy aiming
      to increase power efficiency. It compares, in terms of efficiency, the
      traditional use of boost converters to two alternatives that could be implemented
      in future hardware designs.

PMID- 29060738
TI  - Wearable wireless User Interface Cursor-Controller (UIC-C).
AB  - Controlling a computer or a smartphone's cursor allows the user to access a world
      full of information. For millions of people with limited upper extremities motor
      function, controlling the cursor becomes profoundly difficult. Our team has
      developed the User Interface Cursor-Controller (UIC-C) to assist the impaired
      individuals in regaining control over the cursor. The UIC-C is a hands-free
      device that utilizes the tongue muscle to control the cursor movements. The
      entire device is housed inside a subject specific retainer. The user maneuvers
      the cursor by manipulating a joystick imbedded inside the retainer via their
      tongue. The joystick movement commands are sent to an electronic device via a
      Bluetooth connection. The device is readily recognizable as a cursor controller
      by any Bluetooth enabled electronic device. The device testing results have shown
      that the time it takes the user to control the cursor accurately via the UIC-C is
      about three times longer than a standard computer mouse controlled via the hand.
      The device does not require any permanent modifications to the body; therefore,
      it could be used during the period of acute rehabilitation of the hands. With the
      development of modern smart homes, and enhancement electronics controlled by the
      computer, UIC-C could be integrated into a system that enables individuals with
      permanent impairment, the ability to control the cursor. In conclusion, the UIC-C
      device is designed with the goal of allowing the user to accurately control a
      cursor during the periods of either acute or permanent upper extremities
      impairment.

PMID- 29060739
TI  - Feasibility of using the RAPAEL Smart Glove in upper limb physical therapy for
      patients after stroke: A randomized controlled trial.
AB  - We aim to assess the feasibility of using the RAPAEL Smart Glove as an assistive
      tool for therapists in clinical rehabilitation therapy settings and to
      investigate if it can be used to improve the motor recovery rate of stroke
      survivors. Our randomized controlled study involved 13 post-stroke inpatients. An
      experimental treatment consisted of one 30-minute game-assisted therapy and one
      30-minute conventional therapy per day while the control treatment consisted of
      two 30-minute conventional therapies. Each therapy block consisted of 15 days
      over a period of 3 weeks. The measured outcomes were the scores on the Wolf Motor
      Function Test and the active range of motion for the forearm and the wrist. The
      mean Wolf Motor Function Test score for the group that received game therapies as
      well as conventional therapies was significantly higher than that for the group
      who received only conventional therapies. The results suggest that the motor
      recovery rate of the clinical rehabilitation therapies can be improved when
      wearable sensors and therapeutic games are used by therapists in their routine
      therapy practice.

PMID- 29060740
TI  - Assessment of elbow spasticity with surface electromyography and mechanomyography
      based on support vector machine.
AB  - The Modified Ashworth Scale (MAS) is the gold standard in clinical for grading
      spasticity. However, its results greatly depend on the physician evaluations and
      are subjective. In this study, we investigated the feasibility of using support
      vector machine (SVM) to objectively assess elbow spasticity based on both surface
      electromyography (sEMG) and mechanomyography (MMG). sEMG signals and tri-axial
      accelerometer mechanomyography (ACC-MMG) signals were recorded simultaneously on
      patients' biceps and triceps when they extended or bended elbow passively. 39
      post-stroke patients participated in the study, and were divided into four groups
      regarding MAS level (MAS=0, 1, 1+ or 2). The three types of features, root mean
      square (RMS), mean power frequency (MPF), and median frequency (MF), were
      calculated from sEMG and MMG signal recordings. Spearman correlation analysis was
      used to investigate the relationship between the features and spasticity grades.
      The results showed that the correlation between MAS and each of the five features
      (MMG-RMS of the biceps, MMG-RMS of the triceps, the EMG-RMS of the biceps, EMG
      RMS of the triceps, EMG-MPF of the triceps) was significant (p<;0.05). The four
      spasticity grades were identified with SVM, and the classification accuracy of
      SVM with sEMG, MMG, sEMG-MMG were 70.9%, 83.3%, 91.7%, respectively. Our results
      suggest that using the SVM-based method with sEMG and MMG to assess elbow
      spasticity would be suitable for clinical management of spasticity.

PMID- 29060741
TI  - Accurate estimation of joint motion trajectories for rehabilitation using Kinect.
AB  - Kinect as an effective tool for clinical assessment and rehabilitation, suffers
      from drawbacks of lower accuracy of measuring human body kinematic data when
      compared to clinical gold standard motion capture devices. The accuracy of time
      varying 3D locations of a fixed number of body joints obtained from Kinect
      skeletal tracking utility is affected by the presence of noise and precision
      limits of the Kinect depth sensor. In this paper, a framework for improving
      accuracy of Kinect skeletal tracking is proposed, that uses a set of parametric
      models to represent and track the human body. Each of the models represents the
      3D geometric properties of a body segment connecting two adjacent joints. The
      temporal trajectories of the joints are recovered via particle filter-based
      motion tracking of each model. The proposed method was evaluated on Active Range
      of Motion exercises by 7 healthy subjects. The joint motion trajectories obtained
      using the proposed framework exhibit a greater motion smoothness (by 36%) along
      with reduced coefficient of variation of radius (by 34%), and lower value of root
      mean-squared-error (by 53%), when compared to Kinect joint trajectories. This
      indicates an improvement in accuracy of joint motion trajectories using Kinect
      device, rendering it more suitable for clinical assessment and rehabilitation.

PMID- 29060742
TI  - Modeling electrical stimulation of mammalian nerve fibers: A mechanistic versus
      probabilistic approach.
AB  - Electrical neurostimulation is increasingly used over neuropharmacology to treat
      various diseases. Despite efforts to model the effects of electrical stimulation,
      its underlying mechanisms remain unclear. This is because current mechanistic
      models just quantify the effects that the electrical field produces near the
      fiber and do not capture interactions between stimulus-initiated action
      potentials (APs) and underlying physiological activity initiated APs. In this
      study, we aim to quantify and compare these interactions. We construct two
      computational models of a nerve fiber of varying degrees of complexity
      (probabilistic versus mechanistic) each receiving two inputs: the underlying
      physiological activity at one end of the fiber, and the external stimulus applied
      to the middle of the fiber. We then define reliability, R, as the percentage of
      physiological APs that make it to the other end of the nerve fiber. We apply the
      two inputs to the fiber at various frequencies and analyze reliability. We find
      that the probabilistic model captures relay properties for low input frequencies
      (<; 10 Hz) but then differs from the mechanistic model if either input has a
      larger frequency. This is because the probabilistic model only accounts for only
      (i) inter signal loss of excitability and (ii) collisions between stimulus
      initiated action potentials (APs) and underlying physiological activity initiated
      APs. This first step towards modeling the interactions in a nerve fiber opens up
      opportunities towards understanding mechanisms of electrical stimulation
      therapies.

PMID- 29060743
TI  - Quantification method of motor function recovery of fingers by using the device
      for home rehabilitation.
AB  - After leaving hospital, patients can carry out rehabilitation by using
      rehabilitation devices. However, they cannot evaluate the recovery by themselves.
      For this problem, a device which can both carry out the rehabilitation and
      evaluation of the degree of recovery is required. This paper proposes the method
      that quantifies the recovery of the paralysis of fingers to evaluate a patient
      automatically. A finger movement is measured by a pressure sensor on the
      rehabilitation device we have developed. A measured data is used as a time-series
      signal, and the recovery of the paralysis is quantified by calculating the
      dissimilarity between a healthy subject's signal and the patient's signal. The
      results of those dissimilarities are integrated over all finger to be used as a
      quantitative scale of recovery. From the experiment conducted with hemiplegia
      patients and healthy subjects, we could trace the process of the recovery by the
      proposed method.

PMID- 29060745
TI  - Alignment-free sequence comparison using joint frequency and position information
      of k-words.
AB  - This paper proposes a novel alignment-free sequence comparison method to identify
      the genetic relationships of organisms with a high resolution. For an accurate
      comparison, both frequency and position information of k-words are obtained from
      genome sequences in the proposed alignment-free sequence comparison method. Using
      principal component analysis (PCA) and phylogeny analysis, we identify the
      classification performance of proposed method. Then, the phylogenetic trees of
      proposed and conventional schemes are compared with reliable reference tree.

PMID- 29060744
TI  - Identification of differentially expressed genes through a meta-analysis approach
      for oral cancer classification.
AB  - We propose a meta-analysis scheme for identifying differentially expressed genes
      in Oral Squamous Cell Carcinoma (OSCC) from different microarray studies. We
      detect a subset of relevant features and further classify samples under two
      experimental conditions (i.e healthy and cancer samples) for better patient
      stratification. A well-established meta-analysis method is adopted and gene
      expression data sets are derived from a public functional genomics data
      repository. Our primary aim is the accurate identification of up- and down
      regulated genes in order to extract valuable biological information concerning
      the changes in expression between healthy and cancer samples. According to our
      results and the extracted informative gene list, a high classification accuracy
      of healthy and OSCC tumors is achieved with as few genes as possible.
      Furthermore, the proposed scheme implies that the combination of datasets from
      different origins may reduce the estimated percentage of false predictions, while
      the power of gene identification and disease classification is increased.

PMID- 29060746
TI  - Privacy-preserving Chi-squared testing for genome SNP databases.
AB  - In recent years, the importance of privacy protection in genome-wide association
      studies (GWAS) has been increasing. GWAS focuses on identifying single-nucleotide
      polymorphisms (SNPs) associated with certain diseases such as cancer and
      diabetes, and Chi-squared testing can be used for this. However, recent studies
      reported that publishing the p-value or the corresponding chi-squared value of
      analyzed SNPs can cause privacy leakage. Several studies have been proposed for
      the anonymization of the chi-squared value with differential privacy, which is a
      de facto privacy metric in the cryptographic community. However, they can be
      applied to only small contingency tables; otherwise, they lose a lot of useful
      information. We propose novel anonymization methods: Rand-Chi and RandChiDist,
      and these methods are experimentally evaluated using real data sets.

PMID- 29060747
TI  - MotifMark: Finding regulatory motifs in DNA sequences.
AB  - The interaction between proteins and DNA is a key driving force in a significant
      number of biological processes such as transcriptional regulation, repair,
      recombination, splicing, and DNA modification. The identification of DNA-binding
      sites and the specificity of target proteins in binding to these regions are two
      important steps in understanding the mechanisms of these biological activities. A
      number of high-throughput technologies have recently emerged that try to quantify
      the affinity between proteins and DNA motifs. Despite their success, these
      technologies have their own limitations and fall short in precise
      characterization of motifs, and as a result, require further downstream analysis
      to extract useful and interpretable information from a haystack of noisy and
      inaccurate data. Here we propose MotifMark, a new algorithm based on graph theory
      and machine learning, that can find binding sites on candidate probes and rank
      their specificity in regard to the underlying transcription factor. We developed
      a pipeline to analyze experimental data derived from compact universal protein
      binding microarrays and benchmarked it against two of the most accurate motif
      search methods. Our results indicate that MotifMark can be a viable alternative
      technique for prediction of motif from protein binding microarrays and possibly
      other related high-throughput techniques.

PMID- 29060748
TI  - Classification of various genomic sequences based on distribution of repeated k
      word.
AB  - In order to extract phylogenetic information from DNA sequences, alignment-free
      methods and alignment-based methods are used. Alignment-based methods have high
      complexity and conventional alignment-free methods have low accuracy. In this
      paper, a new alignment-free method based on the distribution of repeated k-word
      measure is proposed. This novel measure is based on k-words and its multiple
      repeated words. We can get higher performance than conventional word count
      methods in case of using proposed scheme while maintaining total time complexity.
      The proposed measure shows better performance compared to conventional alignment
      free methods with respect to RF distance.

PMID- 29060749
TI  - Predicting rapid progression of Parkinson's Disease at baseline patients
      evaluation.
AB  - The rate of Parkinson's Disease (PD) progression in the initial post-diagnosis
      years can vary significantly. In this work, a methodology for the extraction of
      the most informative features for predicting rapid progression of the disease is
      proposed, using public data from the Parkinson's Progression Markers Initiative
      (PPMI) and machine learning techniques. The aim is to determine if a patient is
      at risk of expressing rapid progression of PD symptoms from the baseline
      evaluation and as close to diagnosis as possible. By examining the records of 409
      patients from the PPMI dataset, the features with the best predictive value at
      baseline patient evaluation are found to be sleep problems, daytime sleepiness
      and fatigue, motor symptoms at legs, cognition impairment, early axial and facial
      symptoms and in the most rapidly advanced cases speech issues, loss of smell and
      affected leg muscle reflexes.

PMID- 29060750
TI  - Colorimetric recognition for urinalysis dipsticks based on quadratic discriminant
      analysis.
AB  - Detection of biomarkers in urine sample is often conducted by use of dipsticks,
      which provides a qualitative result. Urinalysis involving image recognition and
      data processing has becoming one of the powerful tools in clinical diagnosis.
      This paper presents colorimetric recognition of urinalysis dipsticks based on
      quadratic discriminant analysis (QDA) in order to overcome the drawbacks, such
      as, limited detection area, seriously affected by the external light conditions
      etc. It can decrease the error of color space conversion by directly processing
      the data from the captured image using QDA. The correlation of the sRGB color
      space and the difference of covariance matrix of the acquired data were took into
      account in this discriminant analysis. The results of validation experiments by
      Matlab simulation show that it can effectively identify the similarity between
      the test and reference color on the dipsticks with the color recognition accuracy
      at 97.33%.

PMID- 29060751
TI  - Automatic detection of periodontitis using intra-oral images.
AB  - Periodontitis is a chronic inflammatory disease of the supportive tissues and
      bone surrounding the teeth. In severe cases, it can consequently lead to tooth
      loss. This disease is most prevalent in rural and remote communities where
      regular dental visits are limited. Hence, there's a need for a periodontal
      screening tool for use by allied health professionals outside of dental clinics
      to detect periodontitis for early referral and intervention. In this paper two
      algorithms have been proposed and applied on two independently collected datasets
      in Germany and Australia with 20 and 24 participating subjects respectively; in
      the first algorithm, intra-oral images of before periodontitis treatment have
      been considered as diseased subjects and the images of after treatment have been
      considered as healthy subjects. Using the histogram of pixel intensity as our
      classification feature, the healthy and diseased subjects have been classified
      with an accuracy of 66.7%. In the second algorithm, using the difference between
      the histograms as our classification features, images of "before" and "after"
      treatment have been classified with an accuracy of 91.6%. If used in a smart
      phone application, the first algorithm can help people with limited access to
      dental clinics to be screened for periodontitis by allied health professionals in
      any healthcare setting. The second algorithm may be useful in helping non-dental
      personnel to monitor the progress of periodontal treatment.

PMID- 29060752
TI  - Content-based retrieval for lung nodule diagnosis using learned distance metric.
AB  - Similarity metric of the lung nodules can be useful in differentiating between
      benign and malignant lung nodule lesions on computed tomography (CT). Unlike
      previous computerized schemes, which focus on the features extracting, we
      concentrate on similarity metric of the lung nodules. In this study, we first
      assemble a lung nodule dataset which is from LIDC-IDRI lung CT images. This
      dataset includes 746 lung nodules in which 375 domain radiologists identified
      malignant nodules and 371 domain radiologists-identified benign nodules. Each
      nodule is represented by a vector of 26 texture features. We then propose a
      content-based image retrieval (CBIR) scheme to classify between benign and
      malignant lung nodules with a learned Mahalanobis distance metric. The
      Mahalanobis distance metric as a similarity metric can preserve semantic
      relevance and visual similarity of lung nodules. The CBIR approach uses this
      Mahalanobis distance to search for most similar reference nodules for each
      queried nodule. The majority of votes are then computed to predict the likelihood
      of the queried nodule depicting a malignant lesion. For the classification
      accuracy, the area under the ROC curve (AUC) can achieve as 0.942+/-0.008. The
      recall and precision of benign nodules are 0.860 and 0.889, respectively. The
      recall and precision of malignant nodules are 0.893 and 0.866, respectively.

PMID- 29060753
TI  - 11C-PIB PET image analysis for Alzheimer's diagnosis using weighted voting
      ensembles.
AB  - Alzheimer's Disease (AD) is one of the leading causes of death and dementia
      worldwide. Early diagnosis confers many benefits, including improved care and
      access to effective treatment. However, it is still a medical challenge due to
      the lack of an efficient and inexpensive way to assess cognitive function [1].
      Although research on data from Neuroimaging and Brain Initiative and the
      advancement in data analytics has greatly enhanced our understanding of the
      underlying disease process, there is still a lack of complete knowledge regarding
      the indicative biomarkers of Alzheimer's Disease. Recently, computer aided
      diagnosis of mild cognitive impairment and AD with functional brain images using
      machine learning methods has become popular. However, the prediction accuracy
      remains unoptimistic, with prediction accuracy ranging from 60% to 88% [2,3,6].
      Among them, support vector machine is the most popular classifier. However,
      because of the relatively small sample size and the amount of noise in functional
      brain imaging data, a single classifier cannot achieve high classification
      performance. Instead of using a global classifier, in this work, we aim to
      improve AD prediction accuracy by combining three different classifiers using
      weighted and unweighted schemes. We rank image-derived features according to
      their importance to the classification performance and show that the top ranked
      features are localized in the brain areas which have been found to associate with
      the progression of AD. We test the proposed approach on 11C-PIB PET scans from
      The Alzheimer's Disease Neuroimaging Initiative (ADNI) database and demonstrated
      that the weighted ensemble models outperformed individual models of K-Nearest
      Neighbors, Random Forests, Neural Nets with overall cross validation accuracy of
      86.1% +/- 8.34%, specificity of 90.6% +/- 12.9% and test accuracy of 80.9% and
      specificity 85.76% in classification of AD, mild cognitive impairment and healthy
      elder adults.

PMID- 29060755
TI  - Imaging genetics approach to predict progression of Parkinson's diseases.
AB  - Imaging genetics is a tool to extract genetic variants associated with both
      clinical phenotypes and imaging information. The approach can extract additional
      genetic variants compared to conventional approaches to better investigate
      various diseased conditions. Here, we applied imaging genetics to study
      Parkinson's disease (PD). We aimed to extract significant features derived from
      imaging genetics and neuroimaging. We built a regression model based on extracted
      significant features combining genetics and neuroimaging to better predict
      clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high
      correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36)
      between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123I-Ioflupane
      SPECT) predictors of regression model were computed from independent component
      analysis approach. Genetic features were computed using image genetics approach
      based on identified neuroimaging features as intermediate phenotypes. Joint
      modeling of neuroimaging and genetics could provide complementary information and
      thus have the potential to provide further insight into the pathophysiology of
      PD. Our model included newly found neuroimaging features and genetic variants
      which need further investigation.

PMID- 29060754
TI  - Touch-free reaching task for Parkinson's disease patients: A motion sensing
      approach.
AB  - The use of motion tracking devices in healthcare is under investigation. Although
      many motion tracking applications have been proposed to monitor the progress of
      rehabilitation, using such technology to quantify the progression or improvement
      of therapies for movement disorders is still scarce. In this study, we introduce
      a touch-free reaching task which uses a motion sensing device. Our motion
      tracking system combines a motion tracking device and visual feedback to
      implement a movement task for the evaluation of the state of motor functions
      impairment symptoms in Parkinson's disease and other movement disorders.

PMID- 29060756
TI  - Development and control of a magnetorheological haptic device for robot assisted
      surgery.
AB  - A prototype magnetorheological (MR) fluid-based actuator has been designed for
      tele-robotic surgical applications. This device is capable of generating forces
      up to 47 N, with input currents ranging from 0 to 1.5 A. We begin by outlining
      the physical design of the device, and then discuss a novel nonlinear model of
      the device's behavior. The model was developed using the Hammerstein-Wiener (H-W)
      nonlinear black-box technique and is intended to accurately capture the
      hysteresis behavior of the MR-fluid. Several experiments were conducted on the
      device to collect estimation and validation datasets to construct the model and
      assess its performance. Different estimating functions were used to construct the
      model, and their effectiveness is assessed based on goodness-of-fit and final
      prediction-error measurements. A sigmoid network was found to have a goodness-of
      fit of 95%. The model estimate was then used to tune a PID controller. Two
      control schemes were proposed to eliminate the hysteresis behavior present in the
      MR fluid device. One method uses a traditional force feedback control loop and
      the other is based on measuring the magnetic field using a Hall-effect sensor
      embedded within the device. The Hall-effect sensor scheme was found to be
      superior in terms of cost, simplicity and real-time control performance compared
      to the force control strategy.

PMID- 29060757
TI  - Haptic fMRI: Reliability and performance of electromagnetic haptic interfaces for
      motion and force neuroimaging experiments.
AB  - Haptic interfaces compatible with functional magnetic resonance imaging (Haptic
      fMRI) promise to enable rich motor neuroscience experiments that study how humans
      perform complex manipulation tasks. Here, we present a large-scale study (176
      scans runs, 33 scan sessions) that characterizes the reliability and performance
      of one such electromagnetically actuated device, Haptic fMRI Interface 3 (HFI-3).
      We outline engineering advances that ensured HFI-3 did not interfere with fMRI
      measurements. Observed fMRI temporal noise levels with HFI-3 operating were at
      the fMRI baseline (0.8% noise to signal). We also present results from HFI-3
      experiments demonstrating that high resolution fMRI can be used to study spatio
      temporal patterns of fMRI blood oxygenation dependent (BOLD) activation. These
      experiments include motor planning, goal-directed reaching, and visually-guided
      force control. Observed fMRI responses are consistent with existing literature,
      which supports Haptic fMRI's effectiveness at studying the brain's motor regions.

PMID- 29060758
TI  - Grasper integrated tri-axial force sensor system for robotic minimally invasive
      surgery.
AB  - This paper describes the design, microfabrication, and characterization of a
      miniature force sensor for providing tactile feedback in robotic surgical
      systems. We demonstrate for the first time a microfabricated sensor that can
      provide triaxial sensing (normal, x-shear, y-shear) in a single sensor element
      that can be integrated with commercial robotic surgical graspers. Features of
      this capacitive force sensor include differential sensing in the shear directions
      as well as a design where all electrical connections are on one side, leaving the
      backside pristine as the sensing face. The sensor readout is performed by a
      custom-designed printed circuit board with 24-bit resolution. Experimental
      results of sensor performance show normal force resolution of 0.055 N, x-shear
      resolution of 0.25 N, and y-shear resolution of 1.45 N, all of which fall in a
      range of clinically relevant forces.

PMID- 29060759
TI  - Three-axis force sensor with fiber Bragg grating.
AB  - Haptic feedback is critical for many surgical tasks, and it replicates force
      reflections at the surgical site. To meet the force reflection requirements, we
      propose a force sensor with an optical fiber Bragg grating (FBG) for robotic
      surgery. The force sensor can calculate three directional forces of an instrument
      from the strain of three FBGs, even under electromagnetic interference. A
      flexible ring-shape structure connects an instrument tip and fiber strain gages
      to sense three directional force. And a stopper mechanism is added in the
      structure to avoid plastic deformation under unexpected large force on the
      instrument tip. The proposed sensor is experimentally verified to have a sensing
      range from -12 N to 12 N, and its sensitivity was less than 0.06 N.

PMID- 29060760
TI  - Positioning the endoscope in laparoscopic surgery by foot: Influential factors on
      surgeons' performance in virtual trainer.
AB  - We have investigated how surgeons can use the foot to position a laparoscopic
      endoscope, a task that normally requires an extra assistant. Surgeons need to
      train in order to exploit the possibilities offered by this new technique and
      safely manipulate the endoscope together with the hands movements. A realistic
      abdominal cavity has been developed as training simulator to investigate this
      multi-arm manipulation. In this virtual environment, the surgeon's biological
      hands are modelled as laparoscopic graspers while the viewpoint is controlled by
      the dominant foot. 23 surgeons and medical students performed single-handed and
      bimanual manipulation in this environment. The results show that residents had
      superior performance compared to both medical students and more experienced
      surgeons, suggesting that residency is an ideal period for this training.
      Performing the single-handed task improves the performance in the bimanual task,
      whereas the converse was not true.

PMID- 29060761
TI  - Estimation of coherence using the median is robust against EEG artefacts.
AB  - Coherence is a mathematical measure of correlation in the frequency domain,
      commonly used to quantify the oscillatory synchrony of bio-signals such as the
      electroencephalogram (EEG). In biomedical applications, such as assessment of
      functional connectivity, reliable estimation of coherence is of paramount
      importance for studying the function of complex brain networks, as well as their
      disruption in neurological disorders. A major challenge for robust estimation of
      coherence measures is the presence of artefacts. Here, we propose an alternative
      method for finding coherence by estimating auto- and cross-spectral densities
      based on the median or trimmed-mean values across trials, rather than the mean.
      The variance of the average cortico-cortical coherence measures, i.e., the inter
      individual variability, was taken as a measure of robustness and tested on
      resting-state recordings from 34 healthy individuals, both without screening, as
      well as after screening by a statistical thresholding artefact rejection. The
      variability of average coherence in individual channels and frequency bands
      decreased by using the median-based estimation of coherence. Averaged across all
      channels and frequency bands, the variability of coherence estimates based on
      median was significantly lower than mean-based estimates for both unscreened data
      (F = 9.28, p = 0.003, 1-beta0.05 = 0.98) and screened data (F = 6.58, p = 0.01, 1
      beta0.05 = 0.91). Moreover, the variability for median-based estimates was almost
      identical for unscreened and screened data (F = 0.004, p = 0.95), suggesting that
      coherence based on median without artefact rejection might be sufficient for
      robust estimation of coherence.

PMID- 29060762
TI  - Brain connectivity networks at the basis of human attention components: An EEG
      study.
AB  - The Attention Network Task (ANT) was developed to disentangle the three
      components of attention identified in the Posner's theoretical model (alerting,
      orienting and executive control) and to measure the corresponding behavioral
      efficiency. Several fMRI studies have already provided evidences on the
      anatomical separability and interdependency of these three networks, and EEG
      studies have also unveiled the associated brain rhythms. What is still missing is
      a characterization of the brain circuits subtending the attentional components in
      terms of directed relationships between the brain areas and their frequency
      content. Here, we want to exploit the high temporal resolution of the EEG,
      improving its spatial resolution by means of advanced source localization
      methods, and to integrate the resulting information by a directed connectivity
      analysis. The results showed in the present study demonstrate the possibility to
      associate a specific directed brain circuit to each attention component and to
      identify synthetic indices able to selectively describe their neurophysiological,
      spatial and spectral properties.

PMID- 29060763
TI  - Graph theoretical analysis of EEG functional network during multi-workload flight
      simulation experiment in virtual reality environment.
AB  - The research field of mental workload has attracted abundant researchers as
      mental workload plays a crucial role in real-life performance and safety. While
      previous studies have examined the neural correlates of mental workload in 2D
      scenarios (i.e., presenting stimuli on a computer screen (CS) environment using
      univariate methods (e.g., EEG channel power), it is still unclear of the findings
      of one that uses multivariate approach using graphical theory and the effects of
      a 3D environment (i.e., presenting stimuli on a Virtual Reality (VR)). In this
      study, twenty subjects undergo flight simulation in both CS and VR environment
      with three stages each. After preprocessing, the Electroencephalogram (EEG)
      signals were a connectivity matrix based on Phase Lag Index (PLI) will be
      constructed. Graph theory analysis then will be applied based on their global
      efficiency, local efficiency and nodal efficiency on both alpha and theta band.
      For global efficiency and local efficiency, VR values are generally lower than CS
      in both bands. For nodal efficiency, the regions that show at least marginally
      significant decreases are very different for CS and VR. These findings suggest
      that 3D simulation effects a higher mental workload than 2D simulation and that
      they each involved a different brain region.

PMID- 29060764
TI  - How the workload impacts on cognitive cooperation: A pilot study.
AB  - Cooperation degradation can be seen as one of the main causes of human errors.
      Poor cooperation could arise from aberrant mental processes, such as mental
      overload, that negatively affect the user's performance. Using different levels
      of difficulty in a cooperative task, we combined behavioural, subjective and
      neurophysiological data with the aim to i) quantify the mental workload under
      which the crew was operating, ii) evaluate the degree of their cooperation, and
      iii) assess the impact of the workload demands on the cooperation levels. The
      combination of such data showed that high workload demand impacted significantly
      on the performance, workload perception, and degree of cooperation.

PMID- 29060765
TI  - Community detection: Comparison among clustering algorithms and application to
      EEG-based brain networks.
AB  - Community structure is a feature of complex networks that can be crucial for the
      understanding of their internal organization. This is particularly true for brain
      networks, as the brain functioning is thought to be based on a modular
      organization. In the last decades, many clustering algorithms were developed with
      the aim to identify communities in networks of different nature. However, there
      is still no agreement about which one is the most reliable, and to test and
      compare these algorithms under a variety of conditions would be beneficial to
      potential users. In this study, we performed a comparative analysis between six
      different clustering algorithms, analyzing their performances on a ground-truth
      consisting of simulated networks with properties spanning a wide range of
      conditions. Results show the effect of factors like the noise level, the number
      of clusters, the network dimension and density on the performances of the
      algorithms and provide some guidelines about the use of the more appropriate
      algorithm according to the different conditions. The best performances under a
      wide range of conditions were obtained by Louvain and Leicht & Newman algorithms,
      while Ronhovde and Infomap proved to be more appropriate in very noisy
      conditions. Finally, as a proof of concept, we applied the algorithms under exam
      to brain functional connectivity networks obtained from EEG signals recorded
      during a sustained movement of the right hand, obtaining a clustering of scalp
      electrodes which agrees with the results of the simulation study conducted.

PMID- 29060766
TI  - Modelling interactions between blood pressure and brain activity in preterm
      neonates.
AB  - Hypotension or low blood pressure (BP) is a common problem in preterm neonates
      and has been associated with adverse short and long-term outcomes. Deciding when
      and whether to treat hypotension relies on an understanding of the relations
      between blood pressure and brain function. This study aims to investigate the
      interaction between BP and multichannel EEG in preterm infants less than 32 weeks
      gestational age. The mutual information is chosen to model interaction. This
      measure is independent of absolute values of BP and electroencephalography (EEG)
      power and quantifies the level of coupling between the short-term dynamics in
      both signals. It is shown that while adverse health conditions as measured by
      higher clinical risk indices for babies (CRIB II) are accompanied by consistently
      lower blood pressure (r=0.43), no significant correlation was observed between
      CRIB scores and EEG spectral power. More importantly, the chosen measure of
      interaction between dynamics of EEG and BP was found to be more closely related
      to CRIB scores (r=0.49, p-value=0.012), with higher CRIB score associated with
      lower levels of interaction.

PMID- 29060767
TI  - An analysis method for wearable electrocardiogram measurement based on non
      orthogonal complex wavelet expansion.
AB  - An analysis method for wearable electrocardiogram (ECG) measurement is proposed,
      which is based on the non-orthogonal complex wavelet expansion. The standard
      continuous wavelet transform performs the signal filtering that corresponds to
      the orthogonal projection of the ECG signal onto each of the non-orthogonal
      wavelets. This causes feature leakage from the neighboring wavelet filterbanks
      and degrades the detection accuracy of the QRS complexes or T waves, even though
      the wavelets whose waveforms fit to the morphologies of the ECG signals are
      chosen. The proposed method involves a different signal filtering that
      corresponds to the non-orthogonal projection of the signal onto each wavelet so
      that the filter outputs can be the expansion coefficients of the wavelets to
      approximate the ECG signal. The concept of our proposed method is supported by
      simulation results.

PMID- 29060768
TI  - Smooth bandpass empirical mode decomposition with rolling ball sifting for
      extracting carotid bruits and heart sounds.
AB  - Carotid bruits are systolic sounds associated with turbulent blood flow through
      atherosclerotic stenosis in the neck. They are audible intermittent high
      frequency sounds mixed with low-frequency heart sounds that wax and wane
      periodically. It is a nontrivial problem to extract both bruits and heart sounds
      with high fidelity for further computer-aided analysis. In this paper we propose
      a smooth bandpass empirical mode decomposition (EMD) method to tackle the problem
      in the time domain. First, bandpass EMD is achieved by using a rolling ball
      algorithm to sift the local extrema of chosen time-scales. Second, the local zero
      is smoothed by interpolation with a monotone piecewise cubic spline. Preliminary
      results indicate that the new method is able to extract both carotid bruits and
      heart sounds as visually smooth oscillating components.

PMID- 29060769
TI  - Automatic Atrial Fibrillation detection: A novel approach using discrete wavelet
      transform and heart rate variability.
AB  - Early detection of Atrial Fibrillation (AF) is crucial in order to prevent acute
      and chronic cardiac rhythm disorders. In this study, a novel method for robust
      automatic AF detection (AAFD) is proposed by combining atrial activity (AA) and
      heart rate variability (HRV), which could potentially be used as a screening tool
      for patients suspected to have AF. The method includes an automatic peak
      detection prior to the feature extraction, as well as a noise cancellation
      technique followed by a bagged tree classification. Simulation studies on the MIT
      BIH Atrial Fibrillation database was performed to evaluate the performance of the
      proposed method. Results from these extensive studies showed very promising
      results, with an average sensitivity of 96.51%, a specificity of 99.19%, and an
      overall accuracy of 98.22%.

PMID- 29060770
TI  - Comparison of frequency-based techniques for assessment of baroreceptor
      sensitivity and heart rate variability.
AB  - Heart rate variability (HRV) and baroreceptor sensitivity (BRS) quantify
      autonomic variability in heart pacing and the autonomic response to blood
      pressure changes respectively. By necessity, the signals used to calculate HRV
      and BRS (systolic blood pressure (SBP) and RR interval) have one data point every
      cardiac cycle. Due to inherent variability in heart rate, these are non-uniformly
      sampled data. A number of calculation methods exist that adjust for non-uniform
      sampled signals. This study compared frequency domain methods of HRV and BRS
      calculation to ascertain whether more complex methods resulted in different
      results to simpler methods. Wistar rats (n=10), and rats with induced diabetes
      (n=8) were anesthetized and SBP and RR interval measured for a period of
      approximately 5 minutes. This data were analyzed using the sequence technique
      (for BRS), fast Fourier transform (FFT), non-uniform discrete Fourier transform
      (NDFT) and an extended Lomb-Scargle Periodogram (LSP). There were small but
      significant differences in NDFT from LSP technique for both BRS in the low
      frequency range (p=0.005) and HRV in the high frequency range (p=0.001). The NDFT
      technique was also significantly different to FFT technique for BRS in the low
      frequency range (p=0.023). All other methods were not statistically different.
      However, all techniques showed the same results comparing diabetic to control
      rats. This study shows more complex methods that correct for the non-uniformity
      of the sampling have significant differences but those differences are small to
      the point of not altering findings associated with HRV or BRS.

PMID- 29060771
TI  - Discrimination of multiple stress levels in virtual reality environments using
      heart rate variability.
AB  - People are suffering from various stress during daily living. Stress can cause a
      variety of symptoms, and in severe cases, it can lead to a dangerous disease. For
      this reason, it is essential to develop a simple method to evaluate stress level
      precisely. Popularly, heart rate variability (HRV) is used because it can reflect
      autonomic nervous system (ANS) activity. On the other hand, virtual reality (VR),
      which can provide environments similar to reality, is widely used in laboratory
      based experiments. In this paper, we analyzed the HRV of healthy people by using
      the photoplethysmogram (PPG) while providing diverse stress situations. To detect
      and classify the exact stress levels, extracted HRV features and linear
      discriminant analysis (LDA) were utilized. As a result, high multi-class
      classification accuracy was obtained: Baseline (74%), mild stress (81%), and
      severe stress (82%).

PMID- 29060772
TI  - Contribution of body movements on the heart rate variability during high
      intensity running.
AB  - We studied the association between the heart rate variability (HRV) and the
      subject's movement during high intensity running. HRV is affected by movement,
      and this phenomena is known as cardiolocomotor coupling (CLC). Characterization
      of movement related components on the HRV spectrogram is a principal step toward
      meaningful interpretation of autonomic nervous system (ANS) activity. According
      to the literature, the aliases of the first and second harmonics of the cadence
      frequency are the main contributors affecting HRV. Instead, we found out that
      there is another aliasing component containing significant power in the HRV
      spectrogram. The source of this component might be the arm swings, torso movement
      or any other mechanical movement along the horizontal axis, orthogonal to the
      cadence direction. Our results show that in 13 out of 22 subjects the spectral
      HRV component arising from the alias of the second harmonic of cadence frequency
      (vertical acceleration) accommodates significantly less energy than the component
      related to the alias of the first harmonic of horizontal acceleration. Therefore,
      neglecting this component and/or considering the second harmonic of the cadence
      frequency as more dominant one is not always a valid assumption.

PMID- 29060773
TI  - Detection of sympathoadrenal discharge by parameterisation of skin conductance
      and ECG measurement.
AB  - Detection of sympathoadrenal discharge is valuable for stress monitoring, but
      measuring the circulating adrenaline level directly is inconvenient, making non
      invasive physiological sensors an attractive alternative. Little is known
      however, about their performance in detecting different adrenaline levels. In
      this study, adrenaline measurements over time from 20 subjects * 2 trials were
      compared with skin conductance (SC) from different skin sites and ECG recordings
      from which the heart rate and QT interval were derived. The frequency of
      sudomotor responses (FSR) was derived from the SC recording, and a new composite
      parameter for amplification of synchronous changes in multiple sensor signals was
      calculated for different combinations of FSR from different skin sites, heart
      rate and QT interval. The single and composite parameters were evaluated for
      detection performance of adrenaline levels above 1000, 1500 and 2000 pmol/L. The
      best prediction performance was indicated for the composite parameter using the
      FSR from the abdomen, FSR from the forehead and the heart rate, with a ROC area
      under the curve of 0.93 for the 2000 pmol/L threshold. In conclusion, detection
      of strong sympathoadrenal discharges is feasible with good accuracy during
      resting conditions in comfortable room temperature.

PMID- 29060774
TI  - Regression-based noninvasive estimation of intracranial pressure.
AB  - Monitoring of intracranial pressure (ICP) is indicated in patients with a variety
      of conditions affecting the brain and cerebrospinal fluid space. The measurement
      of ICP, however, is highly invasive as it requires placement of a catheter in the
      brain tissue or cerebral ventricular spaces. Several noninvasive techniques have
      been proposed to overcome this issue, and one class of approaches is based on
      analyzing cerebral blood flow velocity (CBFV) and arterial blood pressure (ABP)
      waveforms to infer ICP. Here, we analyze a physiologic model linking ICP to CBFV
      and ABP and present a regression-based approach to estimating ICP. We tested the
      model on 20 datasets recorded from three patients in intensive care. Our
      estimates achieve a mean error (bias) of -1.12 mmHg and a standard deviation of
      the error of 5.56 mmHg, for a root-mean-square error of 5.68 mmHg, when compared
      against the invasive ICP measurement. Since transcranial Doppler ultrasound based
      CBFV measurements depend on the Doppler angle phi between the direction of the
      ultrasound beam and the (main) direction of blood flow velocity, we investigated
      the robustness of our ICP estimates against variations in phi. Our results show a
      change in the estimated ICP that is <;1 mmHg if we assume phi ~ N(MU; sigma2),
      with MU = 0 and sigma = 10 degrees .

PMID- 29060775
TI  - Correction of tissue oxygen saturations using arterial oxygen levels for
      cerebrovascular autoregulation analysis.
AB  - Adequate perfusion of blood is fundamental to brain tissue viability, and failure
      to appropriately regulate cerebral blood flow is related to neurological damage.
      Cerebral tissue oxygenation is commonly used as a surrogate of cerebral blood
      flow for non-invasive measures of autoregulation, but may only be valid during
      periods of constant oxygen delivery. We present a new algorithm to correct for
      supply oxygen-induced variations in cerebral tissue oxygenation, and we validate
      it by measuring the improved correlation of the corrected tissue oxygenation with
      blood flow. The algorithm corrects tissue oxygenation by calculating its linear
      dependence with arterial oxygen saturation below a baseline level. A porcine
      model (N=8) of hypoxia is used to test the algorithm and compare the tissue
      oxygen correction with a blood flow reference signal. The correction provides
      significant improvement in the correlation between flow and tissue oxygenation
      (Wilcoxon signed rank, p<;0.01), and for the root mean square distance between
      the corrected hypoxic periods and the rSO2-flow regression line (Wilcoxon signed
      rank, p<;0.01). This method allows the correction of tissue oxygenation levels
      used in the non-invasive monitoring of autoregulation.

PMID- 29060776
TI  - Unsupervised gait detection using biomechanical restrictions.
AB  - Quantification of human gait with sensors has enormous potential in health and
      rehabilitation applications. Objective measurement of gait features in the home
      and community can reveal the true nature of impact of disease on activities of
      daily living or response to interventions. Previously reported gait event
      detection methods have achieved good success, yet can produce errors in some
      irregular gait patterns. In this paper, we propose a novel unsupervised detection
      of gait events and gait duration by combining two exclusive processes: (i)
      exploration of gait event candidates based on iterative running of existing
      methods with changing parameters and, (ii) selection of the candidate which
      satisfies gait-specific biomechanical restrictions (e.g., when one leg is in
      swing, another leg is likely to be in stance). We evaluated this approach using
      data from a single-axis gyroscope on the left and right ankles in three
      experimental conditions. The proposed method decreased the timing error for
      detection of gait events (toe off and heel strike) in irregular gait patterns
      compared with the conventional method. It also improved the accuracy of
      measurement of gait duration in a longitudinal free-living dataset and
      distinguishing gait from non-gait actions.

PMID- 29060778
TI  - On a unified point process approach for the characterization of bioelectric
      discrete phenomena.
AB  - This paper discusses a unified method based on the theory of point processes to
      characterize various types of bioelectric discrete signals such as heart beat
      timing, myoelectric activity, discharge of primary sensory neurons or neurons in
      the central nervous systems. The doubly stochastic point processes, in which the
      discrete event occurring intensity is stochastic, forms the most general class to
      characterize the discrete phenomena. In this paper the self-exciting process has
      been shown to be useful to characterize wide range of discrete biosignals. The
      modeling of conditional intensity function is the essential part of the
      characterization. When the intensity has a parametric model, the maximum
      likelihood parameter estimation will be the useful way to characterize the
      phenomena. The effectiveness of the method is demonstrated by a specific modeling
      of the spontaneous neuronal burst discharges recorded from the brain thalamus
      during the neuro surgery. The first approximation model has four parameters
      obtained by the instantaneous nonlinearly transformed sinusoidal function. An
      extended model allows arbitrary periodic intensity with refractory period.
      Predicted interval histograms show good agreement with the observed ones
      indicating the validity of the proposed method.

PMID- 29060777
TI  - Model selection for the Pulse Decomposition Analysis of fingertip
      photoplethysmograms.
AB  - In the analysis of fingertip photoplethysmograms (PPG), the Pulse Decomposition
      Analysis (PDA) has emerged as a powerful tool for the extraction of
      physiologically relevant information from the morphology of single digital volume
      pulse (DVP) cycles. In previously published works on the PDA, many different
      models are suggested. In this work, we conducted a data driven approach to
      address the question of which model to choose for the PDA. For this purpose, we
      compiled an extensive dataset of 7805 single DVP pulses that comprises most
      expectable pulse morphologies and conducted PDA simulations with four different
      basis functions types and a meaningful range of model orders. We then performed
      model selection based on the Corrected Akaike Information Criterion (AICc) with
      the aim of identifying the PDA models that provided the best fit. As a result, we
      found that a PDA model based on the linear superposition of three scaled Gamma
      basis functions was selected as the best fitting model in 28.1% of all pulses.
      The second highest relative selection frequency of 14.4% was achieved by fitting
      two Rayleigh functions. Consequently, we recommend to consider the employment of
      this PDA model in further work on the PDA.

PMID- 29060779
TI  - Hemodynamic response to optogenetic stimulation varied under different stimulus
      parameters.
AB  - The coupling between neuronal activity and cerebral blood flow(CBF), known as
      neurovascular coupling, serves as the basis of functional brain imaging.
      Optogenetics provides a precise and selective approach to manipulate the activity
      in cell-specific neurons. It has been used in neuroscience research for
      comprehensive understanding about the light-evoked neurovascular coupling in
      rodent neuronal circuits. However, the spatiotemporal CBF response
      characteristics under different stimulus parameters such as pulse width and
      frequency remains unclear due to the lack of efficient CBF imaging technology. In
      this work, we used laser speckle contrast imaging(LSCI) to study the
      spatiotemporal hemodynamic response to optogenetic stimulation with different
      pulse widths (5ms, 10ms, 20ms) and frequencies (5Hz, 10Hz, 20Hz) in
      Channelrhodopsin-2(ChR2) expressing rats. The results showed that the averaged
      CBF response generally increased along with higher pulse width or frequency. The
      CBF peak response was significantly higher at 20ms and it took significantly
      shorter time to reach response peak at 5Hz. Our work adds additional insights in
      understanding the cell-specific neurovascular coupling mechanism and provides
      informative reference when applying ChR2 optogenetics in neurological disease
      research.

PMID- 29060780
TI  - Phase-domain photoacoustics eliminating acoustic detection variations.
AB  - As one of the fastest-growing imaging modalities in recent years, photoacoustic
      imaging has attracted tremendous research interest for various applications
      including anatomical, functional and molecular imaging. Majority of the
      photoacoustic imaging systems are based on time-domain pulsed photoacoustic
      method, which utilizes pulsed laser source to induce wideband photoacoustic
      signal revealing optical absorption contrast. An alternative way is frequency
      domain photoacoustic method utilizing chirping modulation of laser intensity to
      achieve lower system cost. In this paper, we report another way of photoacoustic
      method, called phase-domain photoacoustic sensing, which explores the phase
      difference between two consequent intensity-modulated laser pulses induced
      photoacoustic measurements to reveal the optical property. The basic principle is
      introduced, modelled and experimentally validated in this paper, which opens
      another potential pathway to perform photoacoustic sensing and imaging
      eliminating acoustic detection variations beyond the conventional time-domain and
      frequency-domain photoacoustic methods.

PMID- 29060781
TI  - An iterative weighted method based on YALL1 for cone-beam X-ray luminescence
      optical tomography imaging: A phantom experimental study.
AB  - Cone-beam X-ray luminescence optical tomography (CB-XLOT) plays an important role
      in in vivo small animal imaging study, which can non-invasively image the three
      dimensional (3-D) distribution of x-ray-excitable nanophosphors deeply embedded
      in imaged object. However, CB-XLOT suffers from a low spatial resolution due to
      the ill-posed nature of optical reconstruction. To alleviate the ill-posedness of
      reconstruction and improve the imaging performance of XLOT, in this paper, we
      propose an iterative weighted L1 minimization method which is achieved by
      incorporating YALL1 (Your algorithm for L1 norm problems). The physical phantom
      experiment was conducted to evaluate the performance of the proposed method,
      where a custom-made cone-beam XLOT system was used as the imaging platform. The
      experimental results indicate that by applying the proposed iterative weighted
      strategy to YALL1 method, the reconstruction performance of XLOT can be improved
      when compared with the conventional YALL1 method.

PMID- 29060782
TI  - A fast forward solver of fluorescence diffuse optical tomography based on the
      lattice Boltzmann method.
AB  - Fluorescence diffuse optical tomography (FDOT) is a new molecular imaging
      technology, which uses near-infrared light to excite the fluorophore in tissues.
      According to the measurements detected on the surface of imaged object, the
      fluorescent quantum yield as well as lifetime of the fluorescence can be
      reconstructed. However, the reconstruction of FDOT remains a challenging problem
      because the conventional forward solvers are time consuming. Thus, a forward
      model solver that would enable the fast imaging is necessary. This paper
      describes a new forward solver to simulate the propagation of photons in tissues
      based on the lattice Boltzmann method (LBM). This is accomplished by propagation
      photons in tissues guided by the LBM. To evaluate the performance of the proposed
      LBM, based on the numerical simulation, we compared the light distribution
      generated by the LBM with the diffusion equation implemented by COMSOL in four
      different cases. The experimental results indicate that compared to diffusion
      equation, the LBM can reduce the computation time for the forward solver of FDOT
      while preserving the similar accuracy.

PMID- 29060783
TI  - A dual-modality optical coherence tomography and selective plane illumination
      microscopy system for mouse embryonic imaging.
AB  - Both optical coherence tomography (OCT) and selective plane illumination
      microscopy (SPIM) are frequently used in mouse embryonic research for high
      resolution three-dimensional imaging. Each of these imaging methods provide a
      unique and independent advantage: SPIM provides morpho-functional information
      through immunofluorescence and OCT provides a method for whole-embryo 3D imaging.
      In this study, we have combined rotational imaging OCT and SPIM into a single,
      dual-modality device to image E9.5 mouse embryos. The results demonstrate that
      the dual-modality setup is able to provide both anatomical and functional
      information simultaneously for more comprehensive tissue characterization.

PMID- 29060785
TI  - Multiplexed immunohistochemistry image analysis using sparse coding.
AB  - Multiplexed immunohistochemical (IHC) methods have been developed to evaluate
      multiple protein biomarkers in a single formalin-fixed paraffin-embedded (FFPE)
      tissue section. Since distinct populations of resident and recruited immune cells
      in tissues (and tumors) not only regulate progression of malignant disease, these
      also represent targets for novel immune-based therapies; thus, improved tissue
      biomarker assessment evaluating immune responses in situ are needed. To
      objectively identify distinct cell subsets in tissues and tumors, we adopted
      sparse coding approaches enabling modeling of data vectors as sparse linear
      combinations of basis elements, to audit cellular presence and phenotypes using
      image cytometry datasets with unbiased assessments. By doing comparative analyses
      between manual gating (ground truth) and sparse coding, we report that results
      are comparable as obtained by manual gating strategies, and demonstrate
      robustness and objectivity of this novel bioinformatics approach.

PMID- 29060786
TI  - Histopathological image classification with bilinear convolutional neural
      networks.
AB  - The computer-aided quantitative analysis for histopathological images has
      attracted considerable attention. The stain decomposition on histopathological
      images is usually recommended to address the issue of co-localization or aliasing
      of tissue substances. Although the convolutional neural networks (CNN) is a
      popular deep learning algorithm for various tasks on histopathological image
      analysis, it is only directly performed on histopathological images without
      considering stain decomposition. The bilinear CNN (BCNN) is a new CNN model for
      fine-grained classification. BCNN consists of two CNNs, whose convolutional-layer
      outputs are multiplied with outer product at each spatial location. In this work,
      we propose a novel BCNN-based method for classification of histopathological
      images, which first decomposes histopathological images into hematoxylin and
      eosin stain components, and then perform BCNN on the decomposed images to fuse
      and improve the feature representation performance. The experimental results on
      the colorectal cancer histopathological image dataset with eight classes indicate
      that the proposed BCNN-based algorithm is superior to the traditional CNN.

PMID- 29060784
TI  - Label-free hyperspectral imaging and quantification methods for surgical margin
      assessment of tissue specimens of cancer patients.
AB  - Hyperspectral imaging (HSI) is a relatively new modality in medicine and can have
      many potential applications. In this study, we developed label-free hyperspectral
      imaging for tumor margin assessment. HSI data, hypercube (x,y,lambda), consists
      of a series of images of the same field of view that are acquired at different
      wavelengths. Every pixel in the hypercube has an optical spectrum. We collected
      surgical tissue specimens from 16 human subjects who underwent head and neck
      (H&N) cancer surgery. We acquired both HSI, autofluorescence images, and
      fluorescence images with 2-NBDG and proflavine from the specimens. Digitized
      histologic slides were examined by an H&N pathologist. We developed image
      preprocessing and classification methods for HSI data and differentiate cancer
      from benign tissue. The hyperspectral imaging and classification method was able
      to distinguish between cancer and normal tissue from oral cavity with an average
      accuracy of 90+/-8%, sensitivity of 89+/-9%, and specificity of 91+/-6%. This
      study suggests that label-free hyperspectral imaging has great potential for
      surgical margin assessment in tissue specimens of H&N cancer patients. Further
      development of the imaging technology and quantification methods is warranted for
      its application in image-guided surgery.

PMID- 29060787
TI  - Angiosome based time series analysis of deep tissue perfusion using diffuse
      speckle contrast analysis.
AB  - An angiosome is a three dimensional volume of biological tissue which a specific
      artery governs. Although proven useful for vascular surgery, the direct
      relationship between arterial flow and microcirculation in specific angiosome
      remains controversial. Here, we present new optical approach, a four-channel
      diffuse speckle contrast analysis (DSCA) which can simultaneously measure blood
      perfusion at different foot area. Based on the hypothesis that same angiosome
      will support similar low frequency oscillation, we investigated cross-correlation
      among different DSCA channels. Our preliminary results show that the LFO signal
      from the channel closest to posterior tibial artery is leading the signal from
      the other channels.

PMID- 29060788
TI  - Human induced pluripotent stem cell region recognition in microscopy images using
      Convolutional Neural Networks.
AB  - We present a deep learning architecture Convolutional Neural Networks (CNNs) for
      automatic classification and recognition of reprogramming and reprogrammed human
      Induced Pluripotent Stem (iPS) cell regions in microscopy images. The
      differentiated cells that possibly undergo reprogramming to iPS cells can be
      detected by this method for screening reagents or culture conditions in iPS
      induction. The learning results demonstrate that our CNNs can achieve the Top-1
      and Top-2 error rates of 9.2% and 0.84%, respectively, to produce probability
      maps for the automatic analysis. The implementation results show that this
      automatic method can successfully detect and localize the human iPS cell
      formation, thereby yield a potential tool for helping iPS cell culture.

PMID- 29060789
TI  - Analysis of mitochondrial shape dynamics using large deformation diffeomorphic
      metric curve matching.
AB  - Mitochondrial shape changes are essential to mitochondrial functions.
      Quantification of mitochondrial shape changes is essential to understanding
      related physiology and disease mechanisms. In this study, we proposed a new
      automated pipeline for quantifying the shape changing patterns of mitochondria in
      the framework of large deformation diffeomorphic metric mapping for curve. We
      validated the accuracy of our pipeline on 32 mitochondria data, each having 6
      sequential time-lapse frames. The contour of each mitochondrion is modeled by a
      curve consisting of a set of landmark points ranging from 39 to 358, with the
      moving distance between every two consecutive frames quantified for each
      localized point. The sensitivity of the proposed pipeline, with respect to
      different curve discretization, was investigated, with high robustness
      established. In addition, we quantified the uncertainty level of the proposed
      pipeline using 10 fixed mitochondria data with 6 time frames as well, with the
      mean between-frame moving distance found to be smaller than 28 nm for a majority
      of the 10 fixed mitochondria data. This indicates that the proposed pipeline has
      a very low level of uncertainty. The encouraging results from this work suggest
      that the proposed pipeline is potentially a powerful tool for quantifying shape
      dynamics, both globally and locally, of a variety of cellular components.

PMID- 29060790
TI  - Tissue classification in a canine model of Duchenne Muscular Dystrophy using
      quantitative MRI parameters.
AB  - Duchenne Muscular Dystrophy (DMD) is a genetic disorder caused by dystrophin
      protein deficiency. Muscle biopsy is the gold standard to determine the disease
      severity and progression. MRI has shown potential for monitoring disease
      progression or assessing the treatment effectiveness. In this study, multiple
      quantitative MRI parameters were used to classify the tissue components in a
      canine model of DMD disease using histoimmunochemistry analysis as a "ground
      truth". Results show that multiple MRI parameters may be used to reliably
      classify the muscular tissue and generate a high-resolution tissue type maps,
      which can be used as potential non-invasive imaging biomarkers for the DMD.

PMID- 29060791
TI  - Effects of respiration depth on human body radar cross section Using 2.4GHz
      continuous wave radar.
AB  - In this study, it was tested whether deep and shallow breathing has an effect on
      the cardiopulmonary radar cross-section (RCS). Continuous wave radar with
      quadrature architecture at 2.4GHz was used to test 2 human subjects breathing
      deep and shallow for 30 seconds each while seated 2 meters away from the radar. A
      retro-reflective marker was placed on the sternum of each subject and measured by
      infrared motion capture cameras to accurately track displacement of the chest.
      The quadrature radar outputs were processed to find the radius of the arc on the
      IQ plot using a circle-fitting algorithm. Results showed that the effective RCS
      ratio of deep to shallow breathing for subjects 1 and 2 was 6.99 and 2.24
      respectively.

PMID- 29060792
TI  - Monitoring peripheral edema of heart failure patients at home: Device, algorithm,
      and clinic study.
AB  - Continuous monitoring of heart failure (HF) patients is desirable in order to
      better manage their illness and reduce unnecessary hospitalization. A
      comprehensive cloud-based HF patient management system is proposed to collect
      patients' health status information and provide just-in-time intervention. To
      date, an HF patient edema monitoring system prototype, including the device and
      its algorithm, has been developed. The hardware features multiple sensors whose
      data are fused using an edema classification algorithm based on a standard linear
      solid (SLS) edematous tissue model. Clinical data have been collected and
      analyzed to verify the effectiveness of the hardware and software. While the
      analysis results show some promise, full validation of the device and the
      algorithm warrant further study.

PMID- 29060793
TI  - A low-cost video-oculography system for vestibular function testing.
AB  - In order to remain in focus during head movements, vestibular-ocular reflex
      causes eyes to move in the opposite direction to head movement. Disorders of
      vestibular system decrease vision, causing abnormal nystagmus and dizziness. To
      diagnose abnormal nystagmus, various studies have been reported including the use
      of rotating chair tests and videonystagmography. However, these tests are
      unsuitable for home use due to their high costs. Thus, a low-cost video
      oculography system is necessary to obtain clinical features at home. In this
      paper, we present a low-cost video-oculography system using an infrared camera
      and Raspberry Pi board for tracking the pupils and evaluating a vestibular
      system. Horizontal eye movement is derived from video data obtained from an
      infrared camera and infrared light-emitting diodes, and the velocity of head
      rotation is obtained from a gyroscope sensor. Each pupil was extracted using a
      morphology operation and a contour detection method. Rotatory chair tests were
      conducted with our developed device. To evaluate our system, gain, asymmetry, and
      phase were measured and compared with System 2000. The average IQR errors of
      gain, phase and asymmetry were 0.81, 2.74 and 17.35, respectively. We showed that
      our system is able to measure clinical features.

PMID- 29060794
TI  - Modified automatic R-peak detection algorithm for patients with epilepsy using a
      portable electrocardiogram recorder.
AB  - Earlier studies have shown that short term heart rate variability (HRV) analysis
      of ECG seems promising for detection of epileptic seizures. A precise and
      accurate automatic R-peak detection algorithm is a necessity in a real-time,
      continuous measurement of HRV, in a portable ECG device. We used the portable CE
      marked ePatch(r) heart monitor to record the ECG of 14 patients, who were
      enrolled in the videoEEG long term monitoring unit for clinical workup of
      epilepsy. Recordings of the first 7 patients were used as training set of data
      for the R-peak detection algorithm and the recordings of the last 7 patients
      (467.6 recording hours) were used to test the performance of the algorithm. We
      aimed to modify an existing QRS-detection algorithm to a more precise R-peak
      detection algorithm to avoid the possible jitter Qand S-peaks can create in the
      tachogram, which causes error in short-term HRVanalysis. The proposed R-peak
      detection algorithm showed a high sensitivity (Se = 99.979%) and positive
      predictive value (P+ = 99.976%), which was comparable with a previously published
      QRS-detection algorithm for the ePatch(r) ECG device, when testing the same
      dataset. The novel R-peak detection algorithm designed to avoid jitter has very
      high sensitivity and specificity and thus is a suitable tool for a robust, fast,
      real-time HRV-analysis in patients with epilepsy, creating the possibility for
      real-time seizure detection for these patients.

PMID- 29060795
TI  - Real-time estimation of eye gaze by in-ear electrodes.
AB  - Cognitive control of a hearing aid is the topic for several ongoing studies. The
      relevance of these studies should be seen in the light of inadequate steering of
      current hearing aids. While most studies are concerned with auditory attention
      tracking from the electroencephalogram (EEG), a complimentary approach may be to
      use visual attention tracking to steer the devices. Visual attention may be
      characterized by gaze direction, which can be obtained by electrooculography
      (EOG). EOG may be recorded from electrodes placed in the ear canal, termed
      EarEOG. To test the comparison of conventional EOG and EarEOG recordings, we
      conducted two experiments with six subjects. In the first experiment, the
      subjects were instructed to follow a moving dot on the screen moving in large
      saccades. In the second experiment, there were five large targets, and within
      each target, the dot had minor movements. When comparing conventional EOG and
      EarEOG, correlations of 0.9 and 0.91 with standard deviations of 0.02 were
      obtained for the two experiments respectively. To assess the feasibility of using
      EarEOG in real-time, correlation between EarEOG and the timecourse of the dot
      position was performed. When both signals were filtered with the same real-time
      applicable filter, correlations of 0.83 and 0.85 with standard deviations of 0.09
      and 0.05 were found respectively to the two experiments. In conclusion, this
      study provides motivational aspects of using EarEOG to estimate eye gaze, as well
      as it identifies important future challenges in real-time applications to steer
      external devices such as a hearing aid.

PMID- 29060796
TI  - PPG pulse direction determination algorithm for PPG waveform inversion by wrist
      rotation.
AB  - This paper describes photoplethysmography (PPG)-based pulse direction
      determination algorithm on a site of the radial artery using a wrist band. It has
      been well known that PPG is susceptible to noise and motion artifacts in the
      mobile environment and many research efforts have been made to focus on rejection
      of the noise and motion artifacts. However, no research has been performed to
      find PPG pulses when PPG is inverted by wrist movement. We present an algorithm,
      which accurately yields which direction PPG pulses face regardless of wrist
      movement. The algorithm is one step closer to robust real-time PPG pulse
      direction determination for continuous PPG monitoring regardless of body
      movements.

PMID- 29060797
TI  - NFC-enabled, tattoo-like stretchable biosensor manufactured by "cut-and-paste"
      method.
AB  - The wearables industry is lacking in devices that have the ability to provide
      valuable biometrics data in a soft, wireless and disposable system. Such a system
      should be high performance, multifunctional, but battery-free and low cost. Near
      field communication (NFC) is a wireless communication protocol built in many
      smartphones nowadays that can read data from battery-free passive tags. As a
      result, NFC-enabled wearable biosensors have been reported, but they are either
      unstretchable or have to be manufactured by labor- and time-intensive
      photolithography and transfer-printing processes. Using a dry and freeform "cut
      and-paste" method, we have built a wireless and low-cost stretchable biosensor
      that integrates temperature sensor, light source/sensor, NFC chip, and antenna.
      It is battery-free and can be laminated on any part of human skin like a
      temporary transfer tattoo. The sensor can fully follow the stretching and
      compression of skin without mechanical failure or delamination. Thus, it is
      imperceptible to wear and can perform high-fidelity sensing. Potential
      applications include, but are not limited to, skin thermography and photometry.

PMID- 29060798
TI  - Impedimetric investigation of dual electrical properties of reduced graphene
      oxide-based biosensors in the detection of dopamine.
AB  - Because of the properties of high charge mobility, large detection area and
      chemical stability of graphene, it has been applied in many biomedical
      applications. Graphene oxide (GO) with abundant oxygenated functional groups is
      easily to form an aqueous suspension by sonication. Here, the exposed areas on
      the patterned-circuit silicon-based chips were first modified by (3-aminopropyl)
      trimethoxysilane (APTMS) for later chemically immobilized GO. After that,
      solution-based reduction process using hydrazine was used to gain reduced GO
      (RGO)-based biosensors. ESCA survey spectra showed oxygen-containing functional
      groups of GO decreased from 47% to 5.7%, 4.1%, 3.8%, and 3.6% under varied
      reduction times of 30 min, 40 min, 50 min, and 60 min, respectively. D/G
      intensity ratio (ID/IG) in Raman spectra showed 1.03 after 60-min reduction
      process. The 60-min reduction process was further used in the electrical sensing
      experiments. Since different deposited layers of graphene were obtained in our
      experimental processes, 60-min-RGO-based biosensors have been found that those
      immobilized RGO possessed semiconductive property as the layers are less than 11.
      By contrary, when the layers were above 11, the immobilized RGO would resemble
      metallic material. In addition, the impedimetric analyses indicated obvious
      signal responses above 86 kHz and showed a concentration-dependent trend in
      dopamine sensing in physiological phosphate buffered saline (PBS) using 60-min
      RGO-based biosensors which were feature of semiconductor.

PMID- 29060799
TI  - Estimating the lower leg muscle activity from distal biosignals around the
      ankles.
AB  - Electromyogram signals (EMG) can be used not only to measure motions, but also to
      control devices such as exoskeleton robots. Sensor electrodes need to be placed
      on each muscle based on kinematics and anatomical characteristics. Wearable EMG
      measurement approach is also investigated in recent years. Electrodes are fixed
      to the clothes. In this paper, we propose a motion measurement method based on
      propagation characteristics of biopotential signal. An experiment with walking
      and plantar flexion motion as tasks. The results showed that the signals
      calculated from proposed method were comparable with that of conventional method.
      We confirmed that there were few individual differences for calculating the
      signals of tibialis anterior, gastrocnemius and peroneal muscles.

PMID- 29060801
TI  - Analysis of variance to assess statistical significance of Laplacian estimation
      accuracy improvement due to novel variable inter-ring distances concentric ring
      electrodes.
AB  - Concentric ring electrodes have shown promise in non-invasive
      electrophysiological measurement demonstrating their superiority to conventional
      disc electrodes, in particular, in accuracy of Laplacian estimation. Recently, we
      have proposed novel variable inter-ring distances concentric ring electrodes.
      Analytic and finite element method modeling results for linearly increasing
      distances electrode configurations suggested they may decrease the truncation
      error resulting in more accurate Laplacian estimates compared to currently used
      constant inter-ring distances configurations. This study assesses statistical
      significance of Laplacian estimation accuracy improvement due to novel variable
      inter-ring distances concentric ring electrodes. Full factorial design of
      analysis of variance was used with one categorical and two numerical factors: the
      inter-ring distances, the electrode diameter, and the number of concentric rings
      in the electrode. The response variables were the Relative Error and the Maximum
      Error of Laplacian estimation computed using a finite element method model for
      each of the combinations of levels of three factors. Effects of the main factors
      and their interactions on Relative Error and Maximum Error were assessed and the
      obtained results suggest that all three factors have statistically significant
      effects in the model confirming the potential of using inter-ring distances as a
      means of improving accuracy of Laplacian estimation.

PMID- 29060800
TI  - Tumor size and elasticity estimation using Smartphone-based Compression-Induced
      scope.
AB  - A simple-to-use, noninvasive, and risk-free system, which will provide accurate
      identification of potentially life threatening malignant tumors using tactile
      pressure, is developed. The Smartphone-based Compression-Induced (SCI) Scope will
      allow physicians to quickly capture the mechanical properties of a benign or
      malignant tumor with the convenience of a smartphone platform. The size and
      elasticity property is described using estimating methods from the pressure
      induced images of SCI Scope. The device is based on the Apple iPhone 6. The image
      will be captured through a waveguide. The image information in combination with
      the force sensor value will be transmitted wirelessly to a computer for
      processing. The size and elasticity estimation experiments with SCI Scope showed
      that the size estimation error of 2.31% and estimated relative elastic modulus
      error of 23.9%.

PMID- 29060802
TI  - RATT: RFID Assisted Tracking Tile. Preliminary results.
AB  - Behavior is one of the most important aspects of animal life. This behavior
      depends on the link between animals, their nervous systems and their environment.
      In order to study the behavior of laboratory animals several tools are needed,
      but a tracking tool is essential to perform a thorough behavioral study.
      Currently, several visual tracking tools are available. However, they have some
      drawbacks. For instance, when an animal is inside a cave, or is close to other
      animals, the tracking cameras cannot always detect the location or movement of
      this animal. This paper presents RFID Assisted Tracking Tile (RATT), a tracking
      system based on passive Radio Frequency Identification (RFID) technology in high
      frequency band according to ISO/IEC 15693. The RATT system is composed of
      electronic tiles that have nine active RFID antennas attached; in addition, it
      contains several overlapping passive coils to improve the magnetic field
      characteristics. Using several tiles, a large surface can be built on which the
      animals can move, allowing identification and tracking of their movements. This
      system, that could also be combined with a visual tracking system, paves the way
      for complete behavioral studies.

PMID- 29060803
TI  - Analysis of muscle activation in lower extremity for static balance.
AB  - Balance plays an important role for human bipedal locomotion. Degeneration of
      balance control is prominent in stroke patients, elderly adults and even for
      majority of obese people. Design of personalized balance training program, in
      order to strengthen muscles, requires the analysis of muscle activation during an
      activity. In this paper we have proposed an affordable and portable approach to
      analyze the relationship between the static balance strategy and activation of
      various lower extremity muscles. To do that we have considered Microsoft Kinect
      XBox 360 as a motion sensing device and Wii balance board for measuring external
      force information. For analyzing the muscle activation pattern related to static
      balance, participants are asked to do the single limb stance (SLS) exercise on
      the balance board and in front of the Kinect. Static optimization to minimize the
      overall muscle activation pattern is carried out using OpenSim, which is an open
      source musculoskeletal simulation software. The study is done on ten normal and
      ten obese people, grouped according to body mass index (BMI). Results suggest
      that the lower extremity muscles like biceps femoris, psoas major, sartorius,
      iliacus play the major role for both maintaining the balance using one limb as
      well as maintaining the flexion of the other limb during SLS. Further
      investigations reveal that the higher muscle activations of the flexed leg for
      normal group demonstrate higher strength. Moreover, the lower muscle activation
      of the standing leg for normal group demonstrate more headroom for the biceps
      femoris-short-head and psoas major to withstand the load and hence have better
      static balance control.

PMID- 29060804
TI  - A new robotic approach to characterize mechanical impedance and energetic
      passivity of the human ankle during standing.
AB  - This paper presents the quantitative characterization of ankle impedance and
      ankle passivity during upright standing. A novel multi-axis robotic platform
      allows for the quantification of these neuromuscular properties in two degrees-of
      freedom of the ankle, specifically, dorsiflexion-plantarflexion (DP) and
      inversion-eversion (IE). For the slow sinusoid perturbations of low frequencies
      ranging up to 1.5 Hz, ankle impedance was accurately approximated by stiffness
      and damping, while the contribution of inertia and reflex feedback was minimal.
      Ankle stiffness and damping were found to be highly direction dependent, being
      much higher in the DP than IE direction. Ankle stiffness linearly increased with
      co-contraction of ankle muscles. While the same trend was evident for ankle
      damping in the DP direction, no significant changes were observed in the IE
      direction. In addition, the ankle behavior was found to be highly dissipative in
      both DOFs over a wide range of muscle activation for young healthy subjects.
      Characterization results in this study would not only provide an insight into the
      functional contribution of the ankle to the control of postural balance but also
      add valuable information in the development of neuro-rehabilitation and assistive
      devices.

PMID- 29060805
TI  - Design and control of a 3-DOF rehabilitation robot for forearm and wrist.
AB  - This paper presents a 3-DOF compact rehabilitation robot, involving mechanical
      structure design, control system design and gravity compensation analysis. The
      robot can simultaneously provide assistance for pronation/supination(P/S),
      flexion/extension(F/E) and adduction/abduction(A/A) joints rehabilitation
      training. The P/S and F/E joints are designed to be driven by cable transmission
      to gain a high backdrivability, and an adjustment plate is adopted to decrease
      the distance between the rotation axis of F/E joint of the human wrist and the
      robot. In addition, gravity compensation is considered to offset the impact of
      self-gravity on the performance of the controller. A "moving window" control
      strategy based on impedance control is proposed and implemented on the robot. A
      comparison between the "moving window" control and classical impedance control
      indicates that the former has more potential to stimulate the voluntary efforts
      of the participant, and has a less limitation moving in a fixed reference
      trajectory. Meanwhile, the results also validate the feasibility and safety of
      the wrist robot system.

PMID- 29060806
TI  - Estimation of tibialis anterior muscle stiffness during the swing phase of
      walking with various footwear.
AB  - The current study examined stiffness in the tibialis anterior muscle during the
      swing phase of walking while wearing various footwear. Seven healthy young men
      participated in this study. Participants were instructed to walk on a treadmill
      at 3 km/h while wearing sports shoes, slippers, or slippers with belts. The
      common peroneal nerve was electrically stimulated every two steps at toe-off
      during walking. Mechanomyograms (MMGs), electromyograms, and ankle angle were
      measured. Evoked MMG was extracted using a Kalman filter and subtraction of
      walking acceleration. The transfer function from the electrical stimulation to
      the evoked MMG was identified using a singular value decomposition method, and
      the natural frequency of the transfer function was calculated as an index of
      muscle stiffness. The natural frequency did not show a clear relationship with
      footwear type. Four participants showed the lowest natural frequency when they
      wore slippers with belts. The remaining subjects showed the lowest natural
      frequency when they wore slippers or shoes. These contrasting findings may have
      been caused by different degrees of adaptation of participants to the footwear.

PMID- 29060807
TI  - Design of anisotropic pneumatic artificial muscles and their applications to soft
      wearable devices for text neck symptoms.
AB  - Pneumatic artificial muscles (PAMs) are frequently used actuators in soft
      robotics due to their structural flexibility. They are generally characterized by
      the tensile force due to the axial contraction and the radial force with volume
      expansion. To date, most applications of P AMs have utilized axial contractions.
      In contrast, we propose a novel way to control radial expansions of particular P
      AMs using anisotropic behaviors. P AMs generally consist of a cylindrical rubber
      bladder that expands with injection of air and multiple flexible but inextensible
      strings or mesh that surround the bladder to generate axial contraction force. We
      propose methods of generating radial expansion force in two ways. One is to
      control the spatial density of the strings that hold the bladder, and the other
      is to give asymmetric patterns directly to the bladder for geometrical
      anisotropy. To evaluate the performance of the actuators, soft sensors made of a
      hyperelastic material and a liquid conductor were attached to the P AMs for
      measuring local strains and pressures of the PAMs. We also suggest use of the
      proposed PAMs to a wearable therapeutic device for treating text neck symptoms as
      an application. The P AMs were used to exert a pressure to the back of the neck
      to recover the original spinal alignment from the deformed shape.

PMID- 29060808
TI  - Impact of actuator impedance characteristics on motor control of assisted hand
      movements.
AB  - Robotic devices hold potential to improve hand rehabilitation outcome by
      providing consistent sensorimotor training. However, most robotic devices focus
      on simply reproducing 'predefined' kinematics of manual tasks without properly
      considering how human adapts to external assistance, while inherent impedance of
      the actuator could have a significant impact on the neural adaptation of human
      subjects. We thus examined the effects of the impedance characteristics of the
      actuators on human motor adaptation under external assistance. Four male subjects
      with no known impairment of hand function participated in an experiment, in which
      subjects performed hand open tasks (against resistance) while actuators of
      different impedance characteristics (pneumatic vs. motor) were used to provide
      assistance. It was found that the joint coordination pattern under pneumatic
      assistance was more similar to that of voluntary movements. More importantly, the
      pneumatic actuators improved agonist-antagonist ratio during movements. They also
      induced sustained contraction of task-related muscles during hold phase, while
      the activation of all muscles during hold phase decreased under motor assistance,
      possibly due to its poor backdrivability. Our results suggest that pneumatic-type
      actuators with low inherent impedance could provide many benefits compared to
      conventional electric motors, as it could reduce cocontraction of antagonist
      muscles of patients while effectively promoting active participation during
      training.

PMID- 29060809
TI  - Decoding emotional valence from electroencephalographic rhythmic activity.
AB  - We attempt to decode emotional valence from electroencephalographic rhythmic
      activity in a naturalistic setting. We employ a data-driven method developed in a
      previous study, Spectral Linear Discriminant Analysis, to discover the
      relationships between the classification task and independent neuronal sources,
      optimally utilizing multiple frequency bands. A detailed investigation of the
      classifier provides insight into the neuronal sources related with emotional
      valence, and the individual differences of the subjects in processing emotions.
      Our findings show: (1) sources whose locations are similar across subjects are
      consistently involved in emotional responses, with the involvement of parietal
      sources being especially significant, and (2) even though the locations of the
      involved neuronal sources are consistent, subjects can display highly varying
      degrees of valence-related EEG activity in the sources.

PMID- 29060810
TI  - Self-regulation of primary motor cortex activity with motor imagery induces
      functional connectivity modulation: A real-time fMRI neurofeedback study.
AB  - Recent developments in data acquisition of functional magnetic resonance imaging
      (fMRI) have led to rapid preprocessing and analysis of brain activity in a
      quasireal-time basis, what so called real-time fMRI neurofeedback (rtfMRI-NFB).
      This information is fed back to subjects allowing them to gain a voluntary
      control over their own region-specific brain activity. Forty-one healthy
      participants were randomized into an experimental (NFB) group, who received a
      feedback directly proportional to their brain activity from the primary motor
      cortex (M1), and a control (CTRL) group who received a sham feedback. The M1 ROI
      was functionally localized during motor execution and imagery tasks. A resting
      state functional run was performed before and after the neurofeedback training to
      investigate the default mode network (DMN) modulation after training. The NFB
      group revealed increased DMN functional connectivity after training to the
      cortical and subcortical sensory/motor areas (M1/S1 and caudate nucleus,
      respectively), which may be associated with sensorimotor processing of learning
      in the resting state. These results show that motor imagery training through
      rtfMRI-NFB could modulate the DMN functional connectivity to motor-related areas,
      suggesting that this modulation potentially subserved the establishment of motor
      learning in the NFB group.

PMID- 29060811
TI  - Identifying the effects of microsaccades in tripolar EEG signals.
AB  - Microsaccades are tiny, involuntary eye movements that occur during fixation, and
      they are necessary to human sight to maintain a sharp image and correct the
      effects of other fixational movements. Researchers have theorized and studied the
      effects of microsaccades on electroencephalography (EEG) signals to understand
      and eliminate the unwanted artifacts from EEG. The tripolar concentric ring
      electrode (TCRE) sensors are used to acquire TCRE EEG (tEEG). The tEEG detects
      extremely focal signals from directly below the TCRE sensor. We have noticed a
      slow wave frequency found in some tEEG recordings. Therefore, we conducted the
      current work to determine if there was a correlation between the slow wave in the
      tEEG and the microsaccades. This was done by analyzing the coherence of the
      frequency spectrums of both tEEG and eye movement in recordings where
      microsaccades are present. Our preliminary findings show that there is a
      correlation between the two.

PMID- 29060812
TI  - Decreased variability of dynamic phase synchronization in brain networks during
      hand movement.
AB  - Dynamic functional connectivity analysis, a rapidly growing method, has been
      demonstrated to provide new spatiotemporal information about how brain motor
      network would reorganize from rest to motor tasks. Phase synchronization
      analysis, which has been widely applied in EEG-based FC analysis, is a promising
      alternative method in dynamic FC analysis. In this study, fMRI data were recorded
      from 28 healthy volunteers when they are resting and performing hand closing and
      opening (HCO) task. Dynamic FC was estimated by phase synchronization analysis.
      In addition, functional connectivity variability (FCV) was compared between rest
      and HCO to investigate the modulation induced by motor task on dynamics of motor
      related FC and network. Results showed that the FCVs in network-of-interest,
      including default-mode network and motor network, decreased during HCO comparing
      with rest. Our results demonstrated that the unconstrained mental activities,
      which resulted in high FCV during rest, would focus on motor execution during HCO
      and thus led to decreased FCV during HCO.

PMID- 29060813
TI  - EEG-based biometry using steady state visual evoked potentials.
AB  - The use of brain signals for person recognition has in recent years attracted
      considerable interest because of the increased security and privacy these can
      offer when compared to conventional biometric measures. The main challenge lies
      in extracting features from the EEG signals that are sufficiently distinct across
      individuals while also being sufficiently consistent across multiple recording
      sessions. A range of EEG phenomena including eyes open and eyes closed activity,
      visual evoked potentials (VEPs) through image presentation, and other mental
      tasks have been studied for their use in biometry.

PMID- 29060814
TI  - Passive functional mapping guides electrical cortical stimulation for efficient
      determination of eloquent cortex in epilepsy patients.
AB  - Electrical cortical stimulation (ECS) is often used in presurgical evaluation
      procedures for patients suffering from pharmacoresistant epilepsy. Real-time
      functional mapping (RTFM) is an alternative brain mapping methodology that can
      accompany traditional functional mapping approaches like ECS. In this paper, we
      present a combined RTFM/ECS system that aims to exploit the common ground and the
      advantages of the two procedures for improved time/effort effectiveness,
      patients' experience and safety. Using the RTFM and ECS data from four patients
      who suffer epilepsy, we demonstrate that the RTFM-guided ECS procedure
      hypothetically reduces the number of electrical stimulations necessary for
      eloquent cortex detection by 40%.

PMID- 29060815
TI  - Prediction of fatigue-related driver performance from EEG data by deep Riemannian
      model.
AB  - Prediction of the drivers' drowsy and alert states is important for safety
      purposes. The prediction of drivers' drowsy and alert states from
      electroencephalography (EEG) using shallow and deep Riemannian methods is
      presented. For shallow Riemannian methods, the minimum distance to Riemannian
      mean (mdm) and Log-Euclidian metric are investigated, where it is shown that Log
      Euclidian metric outperforms the mdm algorithm. In addition the SPDNet, a deep
      Riemannian model, that takes the EEG covariance matrix as the input is
      investigated. It is shown that SPDNet outperforms all tested shallow and deep
      classification methods. Performance of SPDNet is 6.02% and 2.86% higher than the
      best performance by the conventional Euclidian classifiers and shallow Riemannian
      models, respectively.

PMID- 29060816
TI  - Assessment of auditory impression of the coolness and warmness of automotive HVAC
      noise.
AB  - Noise induced by a heating, ventilation and air conditioning (HVAC) system in a
      vehicle is an important factor that affects the comfort of the interior of a car
      cabin. Much effort has been devoted to reduce noise levels, however, there is a
      need for a new sound design that addresses the noise problem from a different
      point of view. In this study, focusing on the auditory impression of automotive
      HVAC noise concerning coolness and warmness, psychoacoustical listening tests
      were performed using a paired comparison technique under various conditions of
      room temperature. Five stimuli were synthesized by stretching the spectral
      envelopes of recorded automotive HVAC noise to assess the effect of the spectral
      centroid, and were presented to normal-hearing subjects. Results show that the
      spectral centroid significantly affects the auditory impression concerning
      coolness and warmness; a higher spectral centroid induces a cooler auditory
      impression regardless of the room temperature.

PMID- 29060817
TI  - Virtual reality body motion induced navigational controllers and their effects on
      simulator sickness and pathfinding.
AB  - Virtual reality (VR) navigation is usually constrained by plausible simulator
      sickness (SS) and intuitive user interaction. The paper reports on the use of
      four different degrees of body motion induced navigational VR controllers, a
      TiltChair, omni-directional treadmill, a manual wheelchair joystick (VRNChair),
      and a joystick in relation to a participant's SS occurrence and a controller's
      intuitive utilization. Twenty young adult participants utilized all controllers
      to navigate through the same VR task environment in separate sessions. Throughout
      the sessions, SS occurrence was measured from a severity score by a standard SS
      questionnaire and from body sway by a center of pressure path length with eyes
      opened and closed. SS occurrence did not significantly differ among the
      controllers. However, time spent in VR significantly contributed to SS
      occurrence; hence, a few breaks to minimize SS should be interjected throughout a
      VR task. For all task trials, we recorded the participant's travel trajectories
      to investigate each controller's intuitive utilization from a computed traversed
      distance. Shorter traversed distances indicated that participants intuitively
      utilized the TiltChair with a slower speed; while longer traversed distances
      indicated participants struggled to utilize the omni-directional treadmill with a
      unnaturalistic stimulation of gait. Therefore, VR navigation should use
      technologies best suited for the intended age group that minimizes SS, and
      produces intuitive interactions for the participants.

PMID- 29060818
TI  - Hedonic editing and order effect in decision-making with neurometric evaluation.
AB  - Investment decisions are based largely on the information that investors are
      received from the target firm. In this research, we consider both the variable of
      Organization of Information, either segregate or integrate, and the Order of the
      information, either in the order of Negative-Positive or in the order of Positive
      Negative. Three groups of information are tested in the experiment: a piece of
      Big Positive information and a piece of Small Negative information (BP/SN); a
      piece of Big Negative information and a piece of Small Positive (BN/SP); and a
      piece of Small Positive information and a piece of Small Negative information
      (SP/SN). The study applied the gathering of the electroencephalographic rhythms
      variations, as well as the heart rate and galvanic skin response. The neurometric
      indicators here employed were the Approach-Withdrawal (AW) and the Emotional (EI)
      indexes. In SP/SN group, the recency effect is found in AWI. However, when
      receiving information in large scale, either big positive or big negative,
      emotion plays a role during decision-making. In both case of BP/SN and BN/SP,
      emotion is effected by organization of information. In the condition of BP/SN,
      neurometrics AWI result suggests more approach potentials when two pieces of
      information presented integrated. While in the case of BN/SP, we observe the
      influence of both order and organization. Individual favours separation of
      information with the order of Negative-Positive, the recency effect.

PMID- 29060819
TI  - Bayesian multi-subject factor analysis to predict microsleeps from EEG power
      spectral features.
AB  - Prediction of an imminent microsleep has the potential to save lives and prevent
      catastrophic accidents. A microsleep is a brief episode of unintentional
      unconsciousness and, hence, loss of responsiveness. In this study, prediction of
      imminent microsleeps using EEG data from 8 subjects was examined. A novel
      Bayesian algorithm was proposed to identify common components of pre-microsleep
      activity in the EEG in all subjects and predict microsleeps 0.25 s ahead. To
      avoid overfitting, this model incorporates sparsity-promoting priors to
      automatically find the minimum number of components. Due to intractability of
      full Bayesian treatment, variational Bayesian was integrated to approximate
      posterior probabilities. To predict microsleeps, EEG log-power spectral features
      were extracted from a 5-s window. Bayesian multi-subject factor analysis was used
      to extract common microsleep patterns and transform all features into lower
      dimension common-space features. Discrimination between responsive and microsleep
      instances was done with a single linear discriminant analysis (LDA) classifier.
      Performance of the proposed method was evaluated using leave-one-subject-out
      cross-validation. Our prediction system achieved moderate AUCROC and GM of 0.90
      and 0.80, respectively, but with a relatively low precision of 0.29.

PMID- 29060820
TI  - A system for accelerometer-based gesture classification using artificial neural
      networks.
AB  - A great many people suffer from neurological movement disorders that render
      typical hardware interface devices ineffective. A need exists for a universal
      interface device that can be trained to accept a wide range of inputs across
      varying types and severities of movement disorders. In this regard, this paper
      details the design, testing and optimization of an accelerometer-based gesture
      identification system. A Bluetooth-enabled IMU mounted on the wrist provides hand
      motion trajectory information to a local terminal. Several techniques are applied
      to decrease the intra-class variance and reduce classifier complexity including
      filtering, segmentation and temporal scaling. Datasets consisted of 520 training
      samples, 260 validation samples and a further 520 testing samples. A multi-layer
      feed forward artificial neural network (ML-FFNN) was used to classify the input
      space into 26 different classes. Initial system accuracy, using arbitrary
      hyperparameters was 77.69% with final optimized accuracy at 99.42%.

PMID- 29060821
TI  - Stenosis detection and quantification on cardiac CTCA using panoramic MIP of
      coronary arteries.
AB  - In this work, we proposed to demonstrate the entire 3D coronary tree using
      panoramic maximum intensity projection (MIP) of coronary arteries, and to detect
      and quantify coronary stenosis from computed tomography coronary angiography
      (CTCA). The performance of the proposed method was assessed in comparison with
      invasive coronary angiography (ICA) as reference standard. Six anonymized CTCA
      datasets were tested. MIP method achieved a sensitivity of 82% and a specificity
      of 95% for the stenosis detection with a good reproducibility (i.e. Cohen's kappa
      coefficient of 0.74 for the intra-rater agreement, and 0.45 for the inter-raters
      agreement). In stenosis quantification, three image options are provided. The
      original density images resulted in an accuracy of 0.85. The edge map images
      resulted in an accuracy of 0.79. The image combination had a better accuracy of
      0.89 than any single image option. In conclusion, the panoramic MIP provided fast
      and accurate way for the stenosis detection and quantification. It may be helpful
      to assist the radiologist in identifying the location of the greatest narrowing
      in clinical practice.

PMID- 29060822
TI  - Online SVM-based personalizing method for the drowsiness detection of drivers.
AB  - Inter-driver variation is one of major problems of the drowsiness detecting
      system-based on physiological signals. This paper proposes an online support
      vector machine (OSVM)-based method to solve the problem by the inter-driver
      variation. The method personalizes the drowsiness detecting system for a certain
      real user using feedback data from the user. The OSVM selects important data in
      previous training data and retrains itself with new feedback data for the
      personalization. Two OSVMs having different initial training data are
      personalized by the feedback data, and a switching method of the two OSVMs is
      used in the proposed method for low initial error and fast adaptation. Simulation
      was conducted using the data obtained by a wearable device and an indoor driving
      simulator, and the usefulness of the proposed method was validated. The detecting
      accuracy was increased from 72.05 % to 95.66 % on average for 28 subjects. By
      feedback data and the proposed method, more accurate drowsiness detection will be
      possible and it will increase the safety of drivers.

PMID- 29060823
TI  - Intuitive and interpretable visual communication of a complex statistical model
      of disease progression and risk.
AB  - Computer science and machine learning in particular are increasingly lauded for
      their potential to aid medical practice. However, the highly technical nature of
      the state of the art techniques can be a major obstacle in their usability by
      health care professionals and thus, their adoption and actual practical benefit.
      In this paper we describe a software tool which focuses on the visualization of
      predictions made by a recently developed method which leverages data in the form
      of large scale electronic records for making diagnostic predictions. Guided by
      risk predictions, our tool allows the user to explore interactively different
      diagnostic trajectories, or display cumulative long term prognostics, in an
      intuitive and easily interpretable manner.

PMID- 29060824
TI  - A non-exercise based V02max prediction using FRIEND dataset with a neural
      network.
AB  - The main goal of this work is the development of models, based on computational
      intelligence techniques, in particular neural networks, to predict the maximum
      oxygen consumption value. While the maximum oxygen consumption is a direct mark
      of the cardiorespiratory fitness, several studies have also confirmed it also as
      a powerful predictor of risk for adverse outcomes, such as hypertension, obesity,
      and diabetes. Therefore, the existence of simpler and accurate models,
      establishing an alternative to standard cardiopulmonary exercise tests, with the
      potential to be employed in the stratification of the general population in daily
      clinical practice, would be of major importance. In the current study, different
      models were implemented and compared: 1) the traditional Wasserman/Hansen
      equation; 2) linear regression and; 3) non-linear neural networks. Their
      performance was evaluated based on the "FRIEND - Fitness Registry and the
      Importance of Exercise: The National Data Base" [1] being, in the present study,
      a subset of 12262 individuals employed. The accuracy of the models was performed
      through the computation of sensitivity and specificity values. The results show
      the superiority of neural networks in the prediction of maximum oxygen
      consumption.

PMID- 29060825
TI  - Prediction of hip fracture in post-menopausal women using artificial neural
      network approach.
AB  - Hip fracture is one of the most serious health problems among post-menopausal
      women with osteoporosis. It is very difficult to predict hip fracture, because it
      is affected by multiple risk factors. Existing statistical models for predicting
      hip fracture risk yield area under the receiver operating characteristic curve
      (AUC) ~0.7-0.85. In this study, we trained an artificial neural network (ANN) to
      predict hip fracture in one cohort, and validated its predictive performance in
      another cohort. The data for training and validation included age, bone mineral
      density (BMD), clinical factors, and lifestyle factors which had been obtained
      from a longitudinal study that involved 1167 women aged 60 years and above. The
      women had been followed up for up to 10 years, and during the period, the
      incidence of new hip fractures was ascertained. We applied feed-forward neural
      networks to learn from the data, and then used the learning for predicting hip
      fracture. Results of prediction showed that the accuracy of model I (which
      included only lumbar spine and femoral neck BMD) and model II (which included non
      BMD factors) was 82% and 84%, respectively. When both BMD and non-BMD factors
      were combined (Model III), the accuracy increased to 87%. The AUC for model III
      was 0.94. These findings indicate that ANNs are able to predict hip fracture more
      accurately than any existing statistical models, and that ANNs can help stratify
      individuals for clinical management.

PMID- 29060826
TI  - Evaluation of ultrasonic scattering for different cortical bone porosities and
      excitation frequencies: A numerical study.
AB  - Quantitative ultrasound is a promising and relative recent method for the
      assessment of bone. In this work, the interaction of ultrasound with the porosity
      of cortical bone is investigated for different frequencies. Emphasis is given on
      the study of complex scattering effects induced by the propagation of an
      ultrasonic wave in osseous tissues. Numerical models of cortical bone are
      established with a porosity of 0, 5 and 10% corresponding to healthy homogeneous
      bone, healthy inhomogeneous bone and normal ageing, respectively. Different
      excitation frequencies are applied in the range 0.2-1 MHz. The scattering
      amplitude and the acoustic pressure are calculated for multiple angles and
      receiving positions focusing on the backward direction. The results indicate that
      the application of higher frequencies can better distinguish changes in the
      energy distribution in the backward direction due to alterations of the cortical
      porosity.

PMID- 29060827
TI  - A framework for simulating gastric electrical propagation in confocal microscopy
      derived geometries.
AB  - Interstitial Cells of Cajal (ICC) initiate and actively propagate electrical
      events in the gastrointestinal tract known as slow-waves. The slow-waves
      coordinate the contraction of the gastrointestinal tract necessary for breakdown
      and mixing of ingested food. Degradation of the ICC numbers has been linked to
      several gastrointestinal motility disorders. However, limitations in imaging
      techniques and techniques for the quantification of ICC network structure have
      hindered our understanding of these disorders. We evaluated different machine
      learning techniques to segment ICC networks imaged using confocal microscopy. The
      accuracy the segmented networks were then quantified and compared using numerical
      metrics. Structurally realistic finite element meshes were constructed and used
      to simulate the propagation of electrical activation over the tissue blocks. The
      presented framework provides a system to quantify the structure and function of
      an ICC tissue sample. These methods are also applicable to other biological
      tissues and networks.

PMID- 29060828
TI  - Anatomical variations of the stomach effects on electrogastrography.
AB  - Routine screening and accurate diagnosis of chronic gastrointestinal motility
      disorders represents a significant problem in current clinical practice.
      Electrogastrography (EGG) provides a non-invasive option for assessing gastric
      slow waves, as a means of diagnosing gastric dysrhythmias. However, its uptake in
      motility practice has been limited partly due to an incomplete description of how
      the underlying gastric slow waves directly relate to EGG. This study aims to
      quantify the effects of various anatomical orientations of the stomach on EGG
      using a multiscale model of whole-organ slow wave activation and EGG. The
      orientation of the stomach was perturbed over six parameters: x, y, z
      translations and rotations. The perturbed simulations were compared to the
      original simulated model using root-mean-squared (RMS) errors and correlation
      coefficients. Simulations demonstrated that the perturbations had minimal
      influence on EGG, however channels located within close proximity of the stomach
      source were subject to large variation as a result of the perturbations. The
      results indicate that outside a critical area the effects of translation/rotation
      have minimal influence on the EGG, and thus beyond this critical area findings
      should be relatively comparable across patient groups. These findings show
      promise in advancing rational development of improved EGG methods towards a
      normative methodology and the formation of a normative database.

PMID- 29060829
TI  - Image-based fluid dynamics analysis of left ventricle outflow tract pressure
      gradient after deployment transcatheter mitral valve.
AB  - The goal of this study was to develop an image-based model to computational
      investigate blood flow and pressure gradients resulting from left ventricular
      (LV) wall motion after the implantation of a mitral valve (MV) prosthesis. Two
      image-based 3D models were reconstructed from multi-slice computed tomography
      images obtained from patients undergoing transcatheter MV replacement. Navier
      Stokes equations were then used to compute the fluid motion. Outflow tract
      obstruction of the models with MV prosthesis were identified by calculating the
      difference between LV systolic and aortic pressures. It was found that computed
      outflow track obstruction compared well with actual obstruction data obtained
      from two patients. Our study indicates computational modeling can be a valuable
      tool to investigate the optimal placement of prosthetic valves guided by
      individualized anatomical data.

PMID- 29060830
TI  - The Visible Human Project male CAD based computational phantom and its use in
      bioelectromagnetic simulations.
AB  - Use of numerical simulation tools to provide qualitative estimates on
      electromagnetic safety, characterize antenna performance for WBAN applications
      and facilitate ground breaking research on diagnostic and therapeutic
      bioelectrical solutions has steadily grown over the past twenty years. However,
      the accuracy and applicability of such tools are directly proportional to the
      fidelity of the model used during the simulation. This paper describes the
      construction of a new CAD based male computational phantom, the Visible Human
      Project (VHP)-Male model, suitable for use in major commercial electromagnetics
      simulation packages.

PMID- 29060831
TI  - Evaluation of a laser-based sensor for the diagnosis of neurological disorders.
AB  - Involuntary muscle activities like fasciculations or tremor are an indication for
      several neurological disorders. However, currently used techniques for measuring
      those activities are limited due to their invasiveness, the unsuitability for
      measuring a whole body simultaneously and the lack of an objective measurement of
      amplitude and duration of muscle activity. Hence, we developed a new laser-based
      sensor for the remote quantification of muscle activity. In the present paper we
      show a basic evaluation of our system by reference to ultrasound measurements.
      Our results show the detection limits of our remote sensor technology in terms of
      fasciculation size and depth within the muscle. Those results will help us for a
      better interpretation of our measurement results and hold promise for the future
      development of our system.

PMID- 29060832
TI  - A bioimpedance sensing system for in-vivo cancer tissue identification: Design
      and preliminary evaluation.
AB  - Bioimpedance evaluation can provide useful information for biological tissue
      characterization and potentially allows the identification of pathological areas
      within a tissue in-vivo. In this study a new needle-based bioimpedance sensing
      system was designed and developed to provide such capability considering intra
      operative detection of cancerous tissue in the larynx as the primary specific
      application. The system is small, low-power, fully embedded in a printed circuit
      board and based on a disposable concentric electrode needle. These
      characteristics make it appropriate for the envisioned clinical use. In addition,
      the device operates in real-time and offers functionalities allowing the tuning
      of its properties to maximize its sensing capabilities for different
      applications. This includes the possibility to perform bioimpedance measurements
      using a sweep of excitation frequencies or a single frequency. Here, the first
      functionality was used to evaluate the instrument's tissue discrimination
      performance at different frequencies and consequently identify the best frequency
      for such task. The second functionality was used to evaluate the performance of
      the system by obtaining repeated measurements on different locations of specific
      biological tissues. This was done using six different ex-vivo animal tissues and
      an ex-vivo porcine larynx. The bioimpedance measurements acquired were then
      investigated in terms of magnitude and phase. Combined analysis of these two
      terms suggests that it is indeed possible to discriminate between different
      tissues using the developed instrument. This is a highly motivating preliminary
      result that demonstrates the potential of the technology and justify the
      investment of further efforts towards a clinically usable system.

PMID- 29060833
TI  - Automatic characterization of user errors in spirometry.
AB  - Spirometry plays a critical role in characterizing and improving outcomes related
      to chronic lung disease. However, patient error in performing the spirometry
      maneuver, such as from coughing or taking multiple breaths, can lead to
      clinically misleading results. As a result, spirometry must take place under the
      supervision of a trained specialist who can identify and correct patient errors.
      To reduce the need for specialists to coach patients during spirometry, we
      demonstrate the ability to automatically detect four common patient errors.
      Creating separate machine learning classifiers for each error based on features
      derived from spirometry data, we were able to successfully label errors on
      spirometry maneuvers with an F-score between 0.85 and 0.92. Our work is a step
      toward reducing the need for trained individuals to administer spirometry tests
      by demonstrating the ability to automatically detect specific errors and provide
      appropriate patient feedback. This will increase the availability of spirometry,
      especially in low resource and telemedicine contexts.

PMID- 29060834
TI  - Robot-assisted mirroring exercise as a physical therapy for hemiparesis
      rehabilitation.
AB  - The paper suggests a therapeutic device for hemiparesis that combines robot
      assisted rehabilitation and mirror therapy. The robot, which consists of a motor,
      a position sensor, and a torque sensor, is provided not only to the paralyzed
      wrist, but also to the unaffected wrist to induce a symmetric movement between
      the joints. As a user rotates his healthy wrist to the direction of either
      flexion or extension, the motor on the damaged side rotates and reflects the
      motion of the normal side to the symmetric angular position. To verify
      performance of the device, five stroke patients joined a clinical experiment to
      practice a 10-minute mirroring exercise. Subjects on Brunnstrom stage 3 had shown
      relatively high repulsive torques due to severe spasticity toward their neutral
      wrist positions with a maximum magnitude of 0.300kgfm, which was reduced to
      0.161kgfm after the exercise. Subjects on stage 5 practiced active bilateral
      exercises using both wrists with a small repulsive torque of 0.052kgfm only at
      the extreme extensional angle. The range of motion of affected wrist increased as
      a result of decrease in spasticity. The therapeutic device not only guided a
      voluntary exercise to loose spasticity and increase ROM of affected wrist, but
      also helped distinguish patients with different Brunnstrom stages according to
      the size of repulsive torque and phase difference between the torque and the
      wrist position.

PMID- 29060835
TI  - PhoneQuant: A smartphone-based quantitative immunoassay analyser.
AB  - There is a vital need for portable and cost-effective point-of-care (PoC) testing
      technologies that provide reliable and rapid results. Lateral Flow Immunoassays
      (LFIA) are suitable PoC diagnostic tools with the potential for use in a wide
      variety of field applications ranging from uses in clinical diagnostics to aiding
      law enforcement. Quick and reliable diagnosis of non-communicable diseases (NCD)
      like diabetes is vital especially in developing countries like India where the
      burden of these diseases is very high and is increasing day by day. In this
      paper, we have presented the design of smartphone-based fully quantitative LFIA
      analyser, An automatic image processing algorithm is also described. A
      repeatability study was done with stable fluorescence reference cartridges. The
      Coefficient of Variation (CoV) for repeatability study was calculated and it was
      found to be good (<; 1.5%). The instrument was tested with blood samples to
      generate a calibration curve for Glycated Haemoglobin (HbA1c) with respect to
      standard lab instrument. Three different set of settings parameters were used in
      smartphone camera their calibration curve formed. All three curves were linearly
      correlated with R2-value greater than 0.985. Finally, the calibration curve was
      validated through three HbA1c blood sample tests- for each sample, CoV was less
      than 5%. The PhoneQuant analyser is the portable cost-effective solution to
      traditional bulky LFIA analysers and it has good potential to be deployed at
      physician's desk or for in-home PoC testing for quick and reliable diagnosis.

PMID- 29060836
TI  - A new 4-DOF parallel robot for MRI-guided percutaneous interventions: Kinematic
      analysis.
AB  - In this paper, we present the concept of a novel 4-DOF parallel robot for MRI
      guided percutaneous interventions. This system belongs to the class of patient
      mounted robots, with two parallel circular stages along which two actuating
      joints move. As a first step, we present the concept of the robot and its
      kinematic analysis. This robot has the potential of increased rigidity and
      reduced inertial effect compared to its predecessor. It also minimizes the number
      of moving components, which enhances safety during the robot's operation.

PMID- 29060837
TI  - Transient reduction in theta power caused by interictal spikes in human temporal
      lobe epilepsy.
AB  - The inhibitory impacts of spikes on LFP theta rhythms(4-8Hz) are investigated
      around sporadic spikes(SSs) based on intracerebral EEG of 4 REM sleep patients
      with temporal lobe epilepsy(TLE) under the pre-surgical monitoring. Sequential
      interictal spikes in both genesis area and extended propagation pathway are
      collected, that, SSs genesis only in anterior hippocampus(aH)(possible
      propagation pathway in Entorhinal cortex(EC)), only in EC(possible propagation
      pathway in aH), and in both aH and EC synchronously. Instantaneous theta power
      was estimated by using Gabor wavelet transform, and theta power level was
      estimated by averaged over time and frequency before SSs(350ms pre-spike) and
      after SSs(350ms post-spike). The inhibitory effect around spikes was evaluated by
      the ratio of theta power level difference between pre-spike and post-spike to pre
      spike theta power level. The findings were that theta power level was reduced
      across SSs, and the effects were more sever in the case of SSs in both aH and EC
      synchronously than either SSs only in EC or SSs only in aH. It is concluded that
      interictal spikes impair LFP theta rhythms transiently and directly. The work
      suggests that the reduction of theta power after the interictal spike might be an
      evaluation indicator of damage of epilepsy to human cognitive rhythms.

PMID- 29060838
TI  - On the detection of peripheral cyanosis in individuals with distinct levels of
      cutaneous pigmentation.
AB  - Peripheral cyanosis, the purple or blue coloration of hands and feet, can
      represent the initial signs of life-threatening medical conditions such as heart
      failure due to coronary occlusion. This makes its effective detection relevant
      for the timely screening of such conditions. In order to reduce the probability
      of false negatives during the assessment of peripheral cyanosis, one needs to
      consider that the manifestation of its characteristic chromatic attributes can be
      affected by a number of physiological factors, notably cutaneous pigmentation.
      The extent to which cutaneous pigmentation can impair this assessment has not
      been experimentally investigated to date, however. Although the detection of
      peripheral cyanosis in darkly-pigmented individuals has been deemed to be
      impractical, data to support or refute this assertion are lacking in the
      literature. In this paper, we address these issues through controlled in silico
      experiments that allow us to predictively reproduce appearance changes triggered
      by peripheral cyanosis (at different severity stages) on individuals with
      distinct levels of cutaneous pigmentation. Our findings indicate that the degree
      of detection difficulty posed by cutaneous pigmentation can be considerably
      mitigated by selecting the appropriate skin site to perform the observations.

PMID- 29060839
TI  - A new alignment free genome comparison algorithm based on statistically estimated
      feature frequency profile.
AB  - The sequence comparison is an important part in bioinformatics to understand the
      biological property of genome. Although the alignment based sequence comparison
      is traditional and reliable algorithm, alignment free methods have been actively
      researched because of their advantage in terms of computational complexity. In
      this paper, we suggest a new alignment free genome comparison scheme based on
      statistical approach. From sequence components, word frequency information of the
      sequence is estimated. By investigating the relationship between estimated
      frequency information and actual word frequency, the characteristics of the
      sequence are numerically represented. The phylogenetic tree and the sequence
      classification of mammalian sequences are provided to reveal the remarkable
      performance of our statistical algorithm.

PMID- 29060840
TI  - Using convolutional neural networks to explore the microbiome.
AB  - The microbiome has been shown to have an impact on the development of various
      diseases in the host. Being able to make an accurate prediction of the phenotype
      of a genomic sample based on its microbial taxonomic abundance profile is an
      important problem for personalized medicine. In this paper, we examine the
      potential of using a deep learning framework, a convolutional neural network
      (CNN), for such a prediction. To facilitate the CNN learning, we explore the
      structure of abundance profiles by creating the phylogenetic tree and by
      designing a scheme to embed the tree to a matrix that retains the spatial
      relationship of nodes in the tree and their quantitative characteristics. The
      proposed CNN framework is highly accurate, achieving a 99.47% of accuracy based
      on the evaluation on a dataset 1967 samples of three phenotypes. Our result
      demonstrated the feasibility and promising aspect of CNN in the classification of
      sample phenotype.

PMID- 29060841
TI  - Modeling the effects of amiodarone on short QT syndrome variant 2 in the human
      ventricles.
AB  - AIMS: The short QT syndrome (SQTS) is a new genetic disorder associated with
      atrial and ventricular arrhythmias and sudden death. The SQT2, SQTS variant,
      results from a gain-of-function mutation (V307L) in the KCNQ1-encoded potassium
      channel. Although pro-arrhythmogenic effects of SQTS have been characterized,
      less is known about the pharmacology of SQTS. Therefore, this study aims to
      assess the effects of amiodarone on SQT2. METHODS AND RESULTS: The ten Tusscher
      et al. model of the human ventricular action potential (AP) was modified to
      incorporate changes to IKs based on experimental data. Cell models were
      incorporated into heterogeneous one-dimensional (1D) tissue to compute the pseudo
      ECG and the corresponding QT interval. The blocking effects of amiodarone on IKs,
      INa, INaK, ICaL, INaCa, and IKr were modeled using nH (Hill coefficient) and IC50
      values from the literature. At the cellular level, amiodarone both at low and
      high doses prolonged the SQT2 AP duration (APD); at the tissue level, amiodarone
      at a high dose caused QT prolongation to the physiological range, but failed at a
      low dose. CONCLUSIONS: Amiodarone at a high dose produced better therapeutic
      effects on SQT2 than at a low dose. This study provides new evidence that
      amiodarone at a high dose may be a potential pharmacological treatment for SQT2.

PMID- 29060842
TI  - Rendering Problem-Oriented CCD for chronic diseases.
AB  - Clinical Document Architecture (CDA) is an XML-based clinical document standard
      designed to ensure data exchange as well as semantic interoperability of
      healthcare information systems. Continuity care of documents (CCD), a template
      derived from CDA, is designed with the goal of displaying patient records more
      intuitively for clinicians, especially for when the patient has a long history of
      medical care.The rate of chronic patients in the general population has increased
      as longevity has increased substantially in the past few decades, and the trend
      towards longer and more complex medical records has made it time-consuming to
      read patient data even in the CCD document. The problem-oriented medical record
      (POMR) is an easily readable medical record style and it has been widely adopted
      in electronic health record (EHR) services in Europe. Unfortunately, POMR has not
      been integrated with the CCD-compatible representation so far. Hence this paper
      proposes Problem-Oriented CCD (PO-CCD) rendering based on CDA and POMR. To find
      out how a PO-CCD would be viewed by healthcare professionals and healthcare IT
      professionals, we drafted a few Problem-oriented CCD example documents and
      conducted a survey on their impression. Among our 41 respondents, 60% replied
      they would like to view patient charts in our Problem-Oriented CCD rendering side
      by-side with the conventional CCD rather than the conventional CCD alone.

PMID- 29060843
TI  - Automatic diagnosis of melanoma using linear and nonlinear features from digital
      image.
AB  - Melanoma is the most serious type of skin cancer and causes more deaths than
      other forms of skin cancer. It is a tiny small malignant mole that is usually
      black or brown but also appears in other color patterns. Early detection of
      melanoma is key as this is the time period when it is most likely to be cured.
      Due to the advancement of smartphone technology, automatic and efficient
      detection of melanoma mole using a smartphone is an active area of research. In
      this study, we developed an automatic melanoma diagnosis system using images
      captured from the digital camera. Our work differs from other studies in the area
      of segmentation of melanoma region and consideration of non-linear features for
      classification of malignant and benign melanoma. In this paper, a combination of
      Otsu and k-means clustering segmentation methods are applied to automatically
      segment and extract the borders of affected region with satisfactory accuracy.
      Also, we explored and extracted different non-linear features along with color
      and texture features existed in literature from the lesion mole. The
      effectiveness of these features was predicted with a machine learning model
      consisting of five different classifiers. Our model predicted the diagnosis of
      mole with an accuracy of 89.7%, i.e., around 10% more than reported results by
      others (to the best of our knowledge) with the same database.

PMID- 29060844
TI  - Improving ROI detection in photoplethysmographic imaging with thermal cameras.
AB  - Photoplethismographic imaging (PPGi) enables the estimation of heart rate without
      body contact by analyzing the temporal skin color changes from video recordings.
      Motion artifacts and atypical facial characteristics cause poor signals and
      currently limit the applicability of PPGi. We have developed a novel algorithm
      for locating cheek and forehead region of interests (ROI) with the aim to improve
      PPGi during challenging situations. The proposed approach is based on the fusion
      of RGB and far-infrared (FIR) video streams where FIR ROI is used as fall-back
      when RGB alone fails. We validated and compared the algorithm against the
      detection based on single sources, using videos from 8 subjects with
      distinctively different face characteristics. The subject performed three
      scenarios with incremental motion artifact content (head at rest, intensive head
      movements, speaking). The results showed that combining the two imaging sources
      increased the detection rate of cheeks from 75% (RGB) to 92% (RGB+FIR) in the
      challenging intensive head movement scenario. This work demonstrated that FIR
      imaging is complementary to simple RGB imaging and when combined, adds robustness
      to the detection of ROI in PPGi applications.

PMID- 29060845
TI  - Smartphone based automatic organ validation in ultrasound video.
AB  - Telesonography involves transmission of ultrasound video from remote areas to the
      doctors for getting diagnosis. Due to the lack of trained sonographers in remote
      areas, the ultrasound videos scanned by these untrained persons do not contain
      the proper information that is required by a physician. As compared to standard
      methods for video transmission, mHealth driven systems need to be developed for
      transmitting valid medical videos. To overcome this problem, we are proposing an
      organ validation algorithm to evaluate the ultrasound video based on the content
      present. This will guide the semi skilled person to acquire the representative
      data from patient. Advancement in smartphone technology allows us to perform high
      medical image processing on smartphone. In this paper we have developed an
      Application (APP) for a smartphone which can automatically detect the valid
      frames (which consist of clear organ visibility) in an ultrasound video and
      ignores the invalid frames (which consist of no-organ visibility), and produces a
      compressed sized video. This is done by extracting the GIST features from the
      Region of Interest (ROI) of the frame and then classifying the frame using SVM
      classifier with quadratic kernel. The developed application resulted with the
      accuracy of 94.93% in classifying valid and invalid images.

PMID- 29060846
TI  - Considerations of handheld respiratory rate estimation via a stabilized Video
      Magnification approach.
AB  - Respiratory rate can be a vital indicator of illness; however, tracking this is a
      non-trivial process. Phase-based Eulerian Video Magnification (EVM) is an
      exciting spatiotemporal video processing approach able to reveal subtle breathing
      motions within video sequences; however, its results are variant to large motions
      and camera blur. In the case of camera motion, a compensation strategy of
      stabilizing (without smoothing) the video has the may reduce estimation error in
      handheld cases. This work explores the extent of removing motion artefacts and
      its impact on identifying subtle breathing motions. Tests across six indoor
      scenes show a reduction mean breathing estimate error for 4 of 6 cases and
      highlights the sensitivity of this approach to unwanted body movements. The
      results of this project suggest the plausibility that non-smoothing video
      amplification processes can be an effective method to track breathing motion and
      that implementing correction techniques which may allow a smartphone to provide a
      compact, non-invasive, online breathing monitor.

PMID- 29060847
TI  - Neurological activity monitoring based on video inpainting.
AB  - Inpainting-based compression and reconstruction methodology can be applied to
      systems with limited resources to enable continuously monitor neurological
      activity. In this work, an approach based on sparse representations and K-SVD is
      augmented to a video processing in order to improve the recovery quality. That
      was mainly achieved by using another direction of spatial correlation and the
      extraction of cuboids across frames. The implementation of overlapping frames
      between the recorded data blocks avoids rising errors at the boundaries during
      the inpainting-based recovery. Controlling the electrode states per frame plays a
      key role for high data compression and precise recovery. The proposed 3D
      inpainting approach can compete with common methods like JPEG, JPEG2000 or MPEG-4
      in terms of the degree of compression and reconstruction accuracy, which was
      applied on real measured local field potentials of a human patient.

PMID- 29060848
TI  - A study of color illumination effect on the SNR of rPPG signals.
AB  - Remote photoplethysmography (rPPG) can be used to measure cardiac activity by
      detecting the subtle color variation of the human skin tissue using an RGB
      camera. Recent studies have presented the feasibility and proposed multiple
      methods to improve the motion robustness for the subject movements. However,
      enhancing the signal-to-noise ratio (SNR) of the rPPG signal is still an
      important issue for the contactless measurement. In this paper, we conducted an
      experiment to study the lighting effect on the SNR of rPPG signals. The results
      point out that different colors of light sources provide different SNR in each
      RGB channel. By providing the dedicated light sources (lambda= 490-620) nm, the
      SNR of rPPG signals captured from the green color channel can be enhanced. Among
      the tested light sources, light green provides the most significant improvement
      from -11.09 to -6.6 dB compared with the fluorescent light.

PMID- 29060849
TI  - Audible capnometric cues with end-tidal carbon dioxide improve the quality of
      patient monitoring.
AB  - The importance of capnometry and end-tidal carbon dioxide (ETCO2) has been
      underscored in recent years by guidelines as a method to continuously monitor
      adequacy of ventilation during sedation and anesthesia. Guidelines for
      cardiopulmonary resuscitation (CPR) recommend attempts to improve CPR quality if
      ETCO2 is lower than 10 mmHg. ETCO2 is thus a time-critical parameter that may
      benefit from being delivered in real time to health care providers. We performed
      a pilot study to investigate whether the addition of audible capnometric cues
      after each breath enhanced providers' ability to maintain appropriate ventilation
      over conventional capnography. The addition of audible cues was confirmed to
      enhance control of ETCO2 during manual ventilation. We subsequently developed
      five distinct audible capnometric cues corresponding to different levels of
      ETCO2. We performed a study using ten random simulated test cases to confirm
      whether changes between levels as well as the direction of change could be
      distinguished using these audible cues. Audible cues were found to be easily
      distinguishable. 16 evaluators correctly identified presence and direction of
      change in ETCO2 with an average pass rate of 89%. It is anticipated that this
      "ETCO2 Audible Cue" feature will be able to improve the quality of patient
      monitoring, as well help improve the quality of CPR.

PMID- 29060850
TI  - DeepPredict: A deep predictive intelligence platform for patient monitoring.
AB  - A novel platform, DeepPredict, for predicting hospital bed exit events from video
      camera systems is proposed. DeepPredict processes video data with a deep
      convolutional neural network consisting of five main layers: a 1 * 1 3D
      convolutional layer used for generating feature maps from raw video data, a
      context-aware pooling layer used for rectifying data from different camera
      angles, two fully connected layers used for applying pre-trained deep features,
      and an output layer used to provide a likelihood of a bed exit event. Results for
      a model trained on 180 hours of data demonstrate accuracy, sensitivity, and
      specificity of 86.47%, 78.87%, and 94.07%, respectively, when predicting a bed
      exit event up to seven seconds in advance.

PMID- 29060852
TI  - A novel smart lighting clinical testbed.
AB  - A real-time, feedback-capable, variable spectrum lighting system was recently
      installed at the University of New Mexico Hospital to facilitate biomedical
      research on the health impacts of lighting. The system consists of variable
      spectrum troffers, color sensors, occupancy sensors, and computing and
      communication infrastructure, and is the only such clinical facility in the US.
      The clinical environment posed special challenges for installation as well as for
      ongoing maintenance and operations. Pilot studies are currently underway to
      evaluate the effectiveness of the system to regulate circadian phase in subjects
      with delayed sleep-wake phase disorder.

PMID- 29060851
TI  - Design, implementation, and evaluation of a physiological closed-loop control
      device for medically-induced coma.
AB  - Concerns regarding reliability and safety, as well as uncertainties about what
      constitutes adequate performance evaluation, have impeded the clinical
      translation of PCLC devices. We describe an attempt to address these challenges
      through design, implementation, and evaluation of a PCLC device for delivering
      medically-induced coma, with the intention to eventually conduct a clinical
      trial. This device works by automatically adjusting the infusion rate of propofol
      - a general anesthetic - in response to an electroencephalogram (EEG) pattern
      called burst suppression. We also designed and implemented a computational
      patient model which interfaces with hardware and produces realistic EEG signals
      in response to propofol infusion. The computational patient model is used in
      hardware-in-the-loop studies to evaluate the behavior of our PCLC device under
      realistic perturbations. Finally, we have tested the performance of our PCLC
      device in rodents. Results from these studies suggest that closed-loop control of
      medically-induced coma in humans is feasible and robust. Consequently, our work
      produced a PCLC device and relevant pre-clinical evidence in support of a pilot
      clinical trial.

PMID- 29060853
TI  - The challenge of magnetic vagal nerve stimulation for myocardial infarction 
      preliminary clinical trial.
AB  - Numerous studies have shown in animal models that vagal nerve stimulation (VNS)
      strikingly reduces infarct size of acute myocardial infarction (AMI) and prevents
      heart failure. However, the lack of techniques to noninvasively stimulate the
      vagal nerve hinders VNS from clinical applications. Transcranial magnetic
      stimulation is noninvasive and capable of stimulating central neurons in
      patients. In this study, we examined whether the magnetic stimulation could
      noninvasively activate the cervical vagal nerve in healthy human. Sixteen healthy
      males and 4 females were enrolled in this study. We used Magstim Rapid2 with a 70
      mm double coil in the right neck. We randomly assigned the subjects to 5 Hz or 20
      Hz stimulation. We defined the maximum intensity of stimulation (MAX) which is
      the intensity just below the threshold of adverse effects. We defined HALF as a
      half of MAX. Protocols comprised 2 sets of MAX and 2 sets of HALF. Each
      stimulation continued for 3 minutes. We monitored heart rate (HR) and assessed
      the bradycardic response as an index of successful VNS. Nineteen subjects
      completed all protocols. They had no problematic adverse events during and/or
      after magnetic VNS. The magnetic VNS induced transient bradycardic responses in
      some subjects, whereas failed to induce sustained bradycardia in pooled data in
      any settings. Arterial pressure did not change either. Successful magnetic
      stimulation requires technical improvements including narrowing the magnetic
      focus and optimization of stimulation site. These improvements may enable us to
      apply magnetic VNS in the management of AMI.

PMID- 29060854
TI  - Design of a compact collimator and 3D imaging system for a scanning beam low
      energy intraoperative radiation therapy system for pancreatic cancer.
AB  - Intraoperative radiation therapy (IORT) involves delivering high doses of
      radiation directly to tumors while sparing healthy tissues in a surgical setting.
      Current IORT systems are limited in their lack of image guidance and variable
      needs for shielded operating rooms. They also lack the capability to deliver non
      uniform therapeutic radiation to irregular shaped clinical targets. We developed
      a scanning beam IORT system (SBIORT) to overcome these limitations. SBIORT
      consists of a low energy x-ray source, a custom compact dynamic x-ray collimator
      system, a robotic arm, and a 3D surface imaging module. Here we describe the
      design and validation of the compact dynamic x-ray collimator system and the 3D
      surface imaging module for use in SBIORT. The proposed collimator can achieve a
      leaf position accuracy of +/- 0.25 mm (95% confidence interval). Phantom studies
      indicated the 3D surface-imaging module has an accuracy of 1.0 +/- 0.6 mm with
      ability to obtain high resolution surface image within 5 seconds. SBIORT is a
      novel approach to deliver conformal intensity-modulated intraoperative radiation
      therapy.

PMID- 29060855
TI  - Visible forceps manipulator with novel linkage bending mechanism for
      neurosurgery.
AB  - In minimally invasive surgery (MIS), especially the neurosurgery, surgeons often
      suffer from occlusion region problem. Common surgical instruments, like endoscope
      and corresponding operating tools, are hard to solve it due to their size and
      rigid mechanical structure. In this paper, we present a visible forceps
      manipulator with novel linkage bending mechanism, which realizes the flexible
      bending capability and high output force, as well as the integrated endoscopic
      function. We present the simplified experiment to evaluate the results of
      mechanical performance and brain phantom test to evaluate feasibility and
      usefulness in neurosurgery. Preliminary results show that phantom experiments
      using the brain phantom verify the feasibility of the novel manipulator.

PMID- 29060856
TI  - A targeted drug delivery platform for assisting retinal surgeons for treating Age
      related Macular Degeneration (AMD).
AB  - In this paper we present our latest robotic setup, which has been modified for
      sub-retinal interventions. The setup consists of: 1) sub-retinal micro cannula
      with automatic pump; 2) Micromanipulator; 3) patient fixation mechanism and 4)
      clinically compatible workstation. The primary objective of this work is to allow
      ophthalmologists to improve administration of substances such as drugs, stem
      cells and gene cargos to their desired targets in the sub-retinal
      microstructures. Such a delivery method will enable effective treatment of Age
      related Macular Degeneration (AMD). AMD is the leading cause of blindness in
      developed countries and as yet there is no efficient treatment. To validate the
      precision of the system a successful targeted delivery scenario with the proposed
      setup and using an intra-operative OCT integrated microscope in a clinical
      environment is presented in this paper.

PMID- 29060857
TI  - Needle release mechanism enabling multiple insertions with an ultrasound-guided
      prostate brachytherapy robot.
AB  - We present a robotic system for transrectal ultrasound-guided prostate
      brachytherapy that employs a quick release mechanism to enable multiple needles
      to be inserted into the prostate prior to plan optimization. The mechanism
      consists of two actuated fingers that act as needle guides, thereby allowing
      insertion of both parallel and angled needles. Path planning, including
      reordering of needles within a batch, is required to avoid collisions with
      previously inserted needles. We perform two phantom experiments using clinical
      implant plans. The extra time required for the robotic motions, including finger
      actuation, is less than three minutes for the entire procedure. Mean position
      error is measured to be less than 0.5 mm, presumably due to the design of the
      needle guides, which have a toroidal shape to enable needle angulation.

PMID- 29060858
TI  - A Master-Slave control system with workspaces isomerism for teleoperation of a
      snake robot.
AB  - Snake robots can be used to assist experts during surgical operations on internal
      organs via natural orifices. However, real-time control of such robot in Mater
      Slave (MS) teleoperation is a major challenge. Inverse kinematics solution of
      snake robots has being a key challenge towards real time control especially if
      the robot is hyper-redundant. This paper proposes a method that can achieve fast
      and precise inverse kinematics solution for real time control MS teleoperation.
      Monte Carlo method is applied to determine possible positions needed to reach a
      given target point, while best position is chosen based on the optimization
      algorithm. For workspace isomerism, the proposed method automatically determines
      appropriate kinematics mapping for the robots. Experimental results show that the
      method can achieve accurate position tracking in MS teleoperation.

PMID- 29060859
TI  - Statistical modeling on motion trajectories for robotic laparoscopic surgery.
AB  - Learning by demonstration enables a robot to learn and perform tasks from
      kinesthetic demonstrations. Gaussian mixture method with constraints is applied
      in this work to model the motion using its trajectories and enable a robot to
      learn motion skills for a simple surgical task with specific requirement. Tissue
      dividing experiments are demonstrated on a robotic surgical simulation platform
      to collect motion trajectories. The demonstrations are modelled using Gaussian
      Mixture Model. Constraints are also imposed onto the motion model to suit the
      specific requirements for carrying out the surgical task on a virtual patient.
      The robot is demonstrated to be able to learn the surgical skills with the
      statistical model and execute it to complete a virtual surgical task.

PMID- 29060860
TI  - Estimating brain connectivity when few data points are available: Perspectives
      and limitations.
AB  - Methods based on the use of multivariate autoregressive modeling (MVAR) have
      proved to be an accurate and flexible tool for the estimation of brain functional
      connectivity. The multivariate approach, however, implies the use of a model
      whose complexity (in terms of number of parameters) increases quadratically with
      the number of signals included in the problem. This can often lead to an
      underdetermined problem and to the condition of multicollinearity. The aim of
      this paper is to introduce and test an approach based on Ridge Regression
      combined with a modified version of the statistics usually adopted for these
      methods, to broaden the estimation of brain connectivity to those conditions in
      which current methods fail, due to the lack of enough data points. We tested the
      performances of this new approach, in comparison with the classical approach
      based on ordinary least squares (OLS), by means of a simulation study
      implementing different ground-truth networks, under different network sizes and
      different levels of data points. Simulation results showed that the new approach
      provides better performances, in terms of accuracy of the parameters estimation
      and false positives/false negatives rates, in all conditions related to a low
      data points/model dimension ratio, and may thus be exploited to estimate and
      validate estimated patterns at single-trial level or when short time data
      segments are available.

PMID- 29060861
TI  - Connectome pattern alterations with increment of mental fatigue in one-hour
      driving simulation.
AB  - The importance of understanding mental fatigue can be seen from many studies that
      started back in past decades. It is only until recent years has mental fatigue
      been explored through connectivity network analysis using graph theory. Although
      previous studies have revealed certain properties of the mental fatigue network
      via graph theory, some of these findings seemingly conflict with one another. The
      differences in findings could be due to mental fatigue being caused by various
      factors or being analyzed using different methods. So, in this study, to further
      understand the functional connectivity of driving fatigue, a weighted and
      undirected connectivity matrix would be constructed before applying graph theory
      to identify the biomarker from the network property. To obtain data for analysis,
      a 64-channel EEG cap was used to record the brain signals of subjects undergoing
      a one-hour driving simulation. Using the recorded EEG signal, a connectivity
      matrix was constructed using a synchronous method known as phase lag index (PLI)
      for the graph theory analysis. Results from this graph theory analysis showed
      that the synchronous network had increased clustering coefficient and decreased
      path length with the accumulation of mental fatigue. Furthermore, by calculating
      clustering coefficient regionally, its results revealed that the significant
      increase occurred mainly in the parietal and occipital regions of the brain.

PMID- 29060862
TI  - Transcranial cerebellar direct current stimulation: Effects on brain resting
      state oscillatory and network activity.
AB  - Transcranial cerebellar direct current stimulation (tcDCS) can offer new insights
      into the cerebellar function and disorders, by modulating noninvasively the
      activity of cerebellar networks. Taking into account the functional interplay
      between the cerebellum and the cerebral cortex, we addressed the effects of
      unilateral tcDCS (active electrode positioned over the right cerebellar
      hemisphere) on the electroencephalographic (EEG) oscillatory activity and on the
      cortical network organization at resting state. Effects on spectral
      (de)synchronizations and functional connectivity after anodal and cathodal
      stimulation were assessed with respect to a sham condition. A lateralized
      synchronization over the sensorimotor area in gamma band, as well as an increase
      of the network segregation in sensory-motor rhythms and a higher communication
      between hemispheres in gamma band, were detected after anodal stimulation. The
      same measures after cathodal tcDCS returned responses similar to the sham
      condition.

PMID- 29060863
TI  - Asymmetry of hemispheric interdependences in the early hours following unilateral
      stroke: An electrophysiological study in rats.
AB  - Disturbance of interhemispheric interactions after stroke has been widely
      reported. However, the dynamic change in the hyperacute stage of stroke remains
      to be elucidated. In this study, interhemispheric interactions and brain
      asymmetry in the early hours after infarction were investigated in animals from
      the aspect of nonlinear interdependences using bilateral EEG recordings. Both the
      right-to-left and the left-to-right hemispheric interdependences were impaired
      after unilateral stroke, with a significant decrease in the first two hours and a
      low level in the following twenty-two hours. The ipsilesional to contralesional
      interdependence was found more vulnerable to unilateral stroke, and the symmetry
      between the right-to-left and the left-to-right hemispheric interdependences was
      damaged. The brain symmetry index after four hours was significantly correlated
      with the infarct volume at twenty-four hours, suggesting its prognostic role as
      early as four hours post-stroke.

PMID- 29060864
TI  - Estimating directed brain-brain and brain-heart connectivity through globally
      conditioned Granger causality approaches.
AB  - While a large body of research has focused on the study of within-brain
      physiological networks (i.e. brain connectivity) as well as their disease-related
      aberration, few investigators have focused on estimating the directionality of
      these brain-brain interaction which, given the complexity of brain networks,
      should be properly conditioned in order to avoid the high number of false
      positives commonly encountered when using bivariate approaches to brain
      connectivity estimation. Additionally, the constituents of a number of brain
      subnetworks, and in particular of the central autonomic network (CAN), are still
      not completely determined. In this study we present and validate a global
      conditioning approach to reconstructing directed networks using complex synthetic
      networks of nonlinear oscillators. We then employ our framework, along with a
      probabilistic model for heartbeat generation, to characterize the directed
      functional connectome of the human brain and to establish which parts of this
      connectome effect the directed central modulation of peripheral autonomic
      cardiovascular control. We demonstrate the effectiveness of our conditioning
      approach and unveil a top-down directed influence of the default mode network on
      the salience network, which in turn is seen to be the strongest modulator of
      directed autonomic cardiovascular control.

PMID- 29060865
TI  - Simultaneous estimation of the in-mean and in-variance causal connectomes of the
      human brain.
AB  - In recent years, the study of the human connectome (i.e. of statistical
      relationships between non spatially contiguous neurophysiological events in the
      human brain) has been enormously fuelled by technological advances in high-field
      functional magnetic resonance imaging (fMRI) as well as by coordinated world wide
      data-collection efforts like the Human Connectome Project (HCP). In this context,
      Granger Causality (GC) approaches have recently been employed to incorporate
      information about the directionality of the influence exerted by a brain region
      on another. However, while fluctuations in the Blood Oxygenation Level Dependent
      (BOLD) signal at rest also contain important information about the physiological
      processes that underlie neurovascular coupling and associations between disjoint
      brain regions, so far all connectivity estimation frameworks have focused on
      central tendencies, hence completely disregarding so-called in-variance causality
      (i.e. the directed influence of the volatility of one signal on the volatility of
      another). In this paper, we develop a framework for simultaneous estimation of
      both in-mean and in-variance causality in complex networks. We validate our
      approach using synthetic data from complex ensembles of coupled nonlinear
      oscillators, and successively employ HCP data to provide the very first estimate
      of the in-variance connectome of the human brain.

PMID- 29060866
TI  - A marked point process approach for identifying neural correlates of tics in
      Tourette Syndrome.
AB  - We propose a novel interpretation of local field potentials (LFP) based on a
      marked point process (MPP) framework that models relevant neuromodulations as
      shifted weighted versions of prototypical temporal patterns. Particularly, the
      MPP samples are categorized according to the well known oscillatory rhythms of
      the brain in an effort to elucidate spectrally specific behavioral correlates.
      The result is a transient model for LFP. We exploit data-driven techniques to
      fully estimate the model parameters with the added feature of exceptional
      temporal resolution of the resulting events. We utilize the learned features in
      the alpha and beta bands to assess correlations to tic events in patients with
      Tourette Syndrome (TS). The final results show stronger coupling between LFP
      recorded from the centromedian-paraficicular complex of the thalamus and the tic
      marks, in comparison to electrocorticogram (ECoG) recordings from the hand area
      of the primary motor cortex (M1) in terms of the area under the curve (AUC) of
      the receiver operating characteristic (ROC) curve.

PMID- 29060867
TI  - Measuring brain activation by using baseline-normalized event-related spectral
      perturbation in working memory task.
AB  - Understanding the cognitive function of human brain is an important step in
      providing scientific evidence which could help us improve the condition of memory
      disorders, slow down its progress or at least help the patients retain some
      important matters. In this study, we aimed to provide additional scientific
      evidence with more insight on how the brain functions at a good/bad cognitive
      state than the usual statistical analysis. We introduced the brain activation
      measurement using baseline-normalized ERSP to determine the activation of EEG
      data from stimuli. These active points over a period of time could reflect brain
      synchronization due to stimuli. We also demonstrated the use of proposed measure
      on attention working memory data. The results indicate the potential of using the
      proposed measurement in categorizing the brain cognitive state and identifying
      some important factors to provide additional evidence to the field in the future.

PMID- 29060868
TI  - Real-time analysis on ensemble SVM scores to reduce P300-Speller intensification
      time.
AB  - In most Brain-Computer Interface systems, especially the P300-Speller, there must
      be a harmonized balance between the accuracy and the spelling time. One major
      drawback of the classical 36-choice P300-Speller is the slow rate of character
      elicitation. This paper aims to propose a real-time signal processing method to
      decrease the spelling time by exploiting the score margins of the ensemble
      Support Vector Machine classifiers during real-time P300-Speller flashes, rather
      than just getting the classifiers' highest scores. Our experiments were conducted
      on the dataset of the BCI Competition III and resulted in a successful character
      rate of over 96% with just approximately 15 to 20 seconds for each character
      spelling session. As compared with the fixed 31.5 seconds of the best original
      approach of the competition, our proposed method significantly reduces the
      required spelling time by over 30% while maintaining the desired classification
      accuracy.

PMID- 29060869
TI  - Evaluation of logarithmic vs. linear ADCs for neural signal acquisition and
      reconstruction.
AB  - An evaluation of the effectiveness of logarithmic quantization for neural signals
      is performed in this paper. Logarithmic analog to digital converters (ADCs) are
      employed in biomedical applications where signals with high dynamic range are
      recorded. For the same number of bits of a linear ADC, a logarithmic one can
      better resolve smaller signals, at a price of worse accuracy for high amplitudes.
      This feature can also reduce the number of bits required and then allow data
      reduction as well. No study was done to verify the efficacy of such ADCs on
      neural signals in the context of spike sorting. Using simulated and recorded
      publically available data this is done extensively in the paper. Neural signals
      are quantized with linear and logarithmic ADCs. Then using the original signal as
      reference, the new signals are processed with Osort for automated spike sorting.
      The results are compared with the reference to determine whether one of the two
      quantization methods provides some benefits. The result is that logarithmic ADCs
      outperform linear quantization only in the range from 2 to 5 bits. Such low
      resolutions are unfortunately not enough for proper spike sorting, hence
      logarithmic ADCs appear not to provide an improvement over a conventional ADC.

PMID- 29060870
TI  - Quality assessment of 3D visualizations with vertical disparity: An ERP approach.
AB  - In an objective approach for the assessment of quality of experience the neural
      correlates of EEG data are studied when stereoscopic images are presented in
      three different conditions containing vertical disparity. These conditions are
      compared to a similar image in 2D both on the channel level by studying the ERP
      components and on the source level by the localization of the corresponding ERP
      component. Our findings posit that P1 component in the occipital cortex has
      significantly increased in amplitude for 3D condition without vertical disparity
      compared to the 2D condition. According to previous studies, this component
      increases when depth information are added to the stimulus which is in line with
      our findings. However the amplitude of this component has significantly decreased
      for 3D condition with maximum vertical disparity compared to the 3D condition
      without vertical disparity. We have concluded that the perception of stereoscopic
      depth by subjects have decreased in this case due to the distortion introduced by
      vertical disparity. The underlying sources corresponding to P1 component are
      localized. Except for the power differences, the source locations do not differ
      for different conditions.

PMID- 29060871
TI  - Detecting abrupt change in neuronal tuning via adaptive point process estimation.
AB  - Neuronal tuning property such as preferred direction and modulation depth could
      change gradually or abruptly in brain machine interface (BMI). The decoding
      performance will decay in static algorithms where dynamic neuronal tuning
      property is regarded as stationary. Many adaptive algorithms have been proposed
      to update the time-varying decoding parameter with main consideration on the
      decoding performance, but seldom focus on exploring how individual neuronal
      tuning property changes physiologically. We propose a novel adaptive algorithm
      based on sequential Monte Carlo point process estimation to capture the abrupt
      change of neuronal modulation depth and preferred direction. At each time point,
      the tuning parameter is assumed as static with a large probability and searched
      within a local area. Meanwhile, the abrupt change is thought to occur with a
      small probability and explored within a global range. This algorithm is tested on
      synthetic neural data and compared with a static point process algorithm. The
      results show that our adaptive algorithm succeeds in detecting the abrupt change
      in neuronal tuning, which contributes to a better reconstruction of kinematics.

PMID- 29060872
TI  - Statistical modeling of Optical Coherence Tomography images by asymmetric Normal
      Laplace mixture model.
AB  - Optical Coherence Tomography (OCT) is known as a non-invasive and high resolution
      imaging modality in ophthalmology. Effecting noise on the OCT images as well as
      other reasons cause a random behavior in these images. In this study, we
      introduce a new statistical model for retinal layers in healthy OCT images. This
      model, namely asymmetric Normal Laplace (NL), fits well the advent of asymmetry
      and heavy-tailed in intensity distribution of each layer. Due to the layered
      structure of retina, a mixture model is addressed. It is proposed to evaluate the
      fitness criteria called Kull-back Leibler Divergence (KLD) and chi-square test
      along visual results. The results express the well performance of proposed model
      in fitness of data except for 6th and 7th layers. Using a complicated model, e.g.
      a mixture model with two component, seems to be appropriate for these layers. The
      mentioned process for train images can then be devised for a test image by
      employing the Expectation Maximization (EM) algorithm to estimate the values of
      parameters in mixture model.

PMID- 29060873
TI  - Tooth cracks detection and gingival sulcus depth measurement using optical
      coherence tomography.
AB  - The aims of this study were to develop an automatic detection technique for tooth
      cracks and to suggest quantitative methods for measuring gingival sulcus depth
      using swept-source optical coherence tomography (SS-OCT). We evaluated SS-OCT
      with wavelength centered at 1310 nm over a spectral bandwidth of 100 nm at a rate
      of 50 kHz as a new diagnostic tool for the detection of tooth cracks and gingival
      sulcus depth. The reliability of the SS-OCT images was verified by imaging the
      crack in extracted human teeth and gingival sulcus of porcine sample. The SS-OCT
      could automatically detect the position of various cracks and visualize the deep
      periodontal pockets. Therefore, the detection capability of SS-OCT images could
      be useful diagnostic tool for dental cracks and periodontal pockets.

PMID- 29060874
TI  - Smart data augmentation for surgical tool detection on the surgical tray.
AB  - In recent years, several algorithms were proposed to monitor a surgery through
      the automatic analysis of endoscope or microscope videos. This paper aims at
      improving existing solutions for the automated analysis of cataract surgeries,
      the most common ophthalmic surgery, which are performed under a microscope.
      Through the analysis of a video recording the surgical tray, it is possible to
      know which tools are put on or taken from the surgical tray, and therefore which
      ones are likely being used by the surgeon. Combining these observations with
      observations from the microscope video should enhance the overall performance of
      the system. Our contribution is twofold: first, datasets of artificial surgery
      videos are generated in order to train the convolutional neural networks (CNN)
      and, second, two classification methods are evaluated to detect the presence of
      tools in videos. Also, we assess the impact of the manner of building the
      artificial datasets on the tool recognition performance. By design, the proposed
      artificial datasets highly reduce the need for fully annotated real datasets and
      should also produce better performance. Experiments show that one of the proposed
      classification methods was able to detect most of the targeted tools well.

PMID- 29060875
TI  - Pyramid approach for the reduction of parallax-related artefacts in optical
      recordings of moving translucent volumes.
AB  - Functional optical imaging (OI) of intrinsic signals (like blood oxygenation
      coupled reflection changes) and of extrinsic properties of voltage sensitive
      probes (like voltage-sensitive dyes (VSD)) forms a group of invasive neuroimaging
      techniques, that possess up to date the highest temporal and spatial resolution
      on a meso- to macroscopic scale. There are different sources that contribute to
      the OI signal of which many are noise. In our previous works, we have used dense
      optical flow for the reduction of movement artefacts. The translucent surface of
      the cortex allows contributions from multiple depths. Due to the depth offield
      (DOF) effect, we get an implicit relation of depth and 2D frequency components.
      In this work, we introduce registration on the levels of a Laplacian pyramid to
      remove movement artefacts which have different motion components in different
      spatial frequency bands. This aims to resolve artefacts that remain after normal
      registration and are caused e.g. by parallax motion, dead pixels or dust on the
      sensor and other high frequent, moving particles on the cortex surface without
      the compromise of using high smoothness weights.

PMID- 29060876
TI  - Non-rigid registration of Fluorescein Angiography and Optical Coherence
      Tomography via scanning laser ophthalmoscope imaging.
AB  - Fluorescein Angiography (FA) imaging is the gold standard technique for
      neurovascular imaging regarding assessing neurovascular diseases such as Diabetic
      Retinopathy (DR) and Diabetic Macular Edema (DME). On the other hand, as FA
      imaging is invasive and does not provide any depth information, Optical Coherence
      Tomography (OCT) imaging technique is a good complementary for it in diagnosis
      process. To correlate the information of both FA and OCT images, an image
      alignment/registration process is needed. In absence of an automatic registration
      software, the clinician should do intuitive comparison to integrate these data
      which is a subjective and time consuming process. In this paper, we demonstrate a
      non-rigid registration method called multi-step correlation-based registration
      algorithm to automatically register FA and OCT images together. Our algorithm
      consists of two steps including rigid/global and non-rigid/local registration. We
      evaluate our algorithm's performance by labeling Micro-Aneurysm (MA) spots 
      hallmarks of DR- on FA images and determining MA regions on OCT B-scans after
      registration. Our Results show that our algorithm performs accurately regarding
      registration of FA images and OCT B-scans.

PMID- 29060877
TI  - Motion estimation of subcellular structures from fluorescence microscopy images.
AB  - We present an automatic image processing framework to study moving intracellular
      structures from live cell fluorescence microscopy. The system includes the
      identification of static and dynamic structures from time-lapse images using data
      clustering as well as the identification of the trajectory of moving objects with
      a probabilistic tracking algorithm. The method has been successfully applied to
      study mitochondrial movement in neurons. The approach provides excellent
      performance under different experimental conditions and is robust to common
      sources of noise including experimental, molecular and biological fluctuations.

PMID- 29060878
TI  - A wearable textile for respiratory monitoring: Feasibility assessment and
      analysis of sensors position on system response.
AB  - The interest on wearable textiles to monitor vital signs is growing in the
      research field and clinical scenario related to the increasing demands of long
      term monitoring. Despite several smart textile-based solutions have beenproposed
      for assessing the respiratory status, only a limitednumber of devices allow the
      respiratory monitoring in a harshenvironment or in different positions of the
      human body.In this paper, we investigated the performances of a smarttextile for
      respiratory rate monitoring characterized by 12 fiberoptic sensors (i.e., fiber
      Bragg grating) placed on specificlandmarks for compartmental analysis of the
      chest wallmovements during quiet breathing. We focused on the analysisof the
      influence of sensor position on both peak-to-peakamplitude of sensors output and
      accuracy of respiratory ratemeasurements. This analysis was performed on
      twoparticipants, who wore the textile in two positions (i.e., standingand
      supine). Bland-Altman analysis on respiratory rate showedpromising results
      (better than 0.3 breaths per minute).Referring to the peak-to-peak output
      amplitude, the abdomencompartment showed the highest excursions in both
      theenrolled participants and positions.Our findings open up new approaches to
      design and developsmart textile for respiratory rate monitoring.

PMID- 29060879
TI  - Electromagnetic disturbances rejection with single skin contact in the context of
      ECG measurements with cooperative sensors.
AB  - Classical approaches to make high-quality measurements of biopotential signals
      require the use of shielded or multi-wire cables connecting the electrodes to a
      central unit in a star arrangement. Consequently, increasing the number of leads
      increases cabling and connector complexity which is not only limiting patient
      comfort but also anticipated as the main limiting factor for future
      miniaturization and cost reduction of tomorrow's wearables. We have recently
      introduced a novel sensing architecture that significantly reduces cabling
      complexity by eliminating shielded or multi-wire cables as well as by allowing
      simple connectors thanks to a bus arrangement. In this architecture, electrodes
      are replaced by so-called cooperative sensors. However, in this design, one of
      the cooperative sensors needs to be equipped with two contacts with the skin for
      proper common mode rejection, thus making its miniaturization problematic. This
      paper presents a novel common mode rejection principle which overcomes this
      limitation. When compared to others, the suggested approach is advantageous as it
      keeps the cabling complexity to its minimum. First measurements demonstrated in a
      real-life scenario the feasibility of this common mode rejection principle for a
      wearable 12-lead electrocardiogram monitoring system.

PMID- 29060881
TI  - Continuous bladder volume monitoring system for wearable applications.
AB  - In this research, we propose a bladder volume monitoring system that can be
      effectively applied for various voiding dysfunctions. Whereas conventional
      systems lack consecutive measurements, the proposed system can continuously
      monitor a user's status even during unconscious sleep. For the convenience, we
      design a simple and comfortable waist-belt-type device by using the body
      impedance analysis (BIA) technique. To support various measurement scenarios, we
      develop applications by connecting the device to a smartphone. To minimize motion
      noises, which are inevitable when monitoring over an extended period, we propose
      a motion artifact reduction algorithm that exploits multiple frequency sources.
      The experimental results show a strong relationship between the impedance
      variation and the bladder volume; this confirms the feasibility of our system.

PMID- 29060880
TI  - A pressure-sensitive palatograph for speech analysis.
AB  - Electropalatography (EPG) is a clinical technique used to monitor contacts
      between the tongue and the hard palate, thus promoting correct articulation
      mechanisms. Currently, employed commercial tools have a good resolution but they
      do not provide contact pressure information. In this work, textile-based sensing
      technologies were employed to realize an innovative EPG tool able to both
      maintain the proper spatial resolution and perform quantitative pressure
      detection. The single sensing unit was developed using a thin polymeric sheet
      with a central hole, sandwiched between two piezoresistive fabric layers. Under
      load application, the two textile layers come into contact and the resistance of
      the sensor reduces significantly, measuring pressure in the range from 0 to 30
      kPa. The complete prototype is composed of 62 sensing units disposed in a matrix
      structure: the dielectric layer contains all the sites arranged in rows and
      columns, according to the topography of the traditional tools, and this layer
      presents on both sides strips of piezoresistive textile. The entire system was
      covered with a thin latex membrane and fixed on a hard custom acrylic palate for
      the experimental characterization. The system was tested on a healthy subject,
      confirming the adequacy and effectiveness of the soft sensing technologies for
      the measuring of the tongue pressure during speech.

PMID- 29060882
TI  - A wearable 12-lead ECG acquisition system with fabric electrodes.
AB  - Continuous electrocardiogram (ECG) monitoring is significant for prevention of
      heart disease and is becoming an important part of personal and family health
      care. In most of the existing wearable solutions, conventional metal sensors and
      corresponding chips are simply integrated into clothes and usually could only
      collect few leads of ECG signals that could not provide enough information for
      diagnosis of cardiac diseases such as arrhythmia and myocardial ischemia. In this
      study, a wearable 12-lead ECG acquisition system with fabric electrodes was
      developed and could simultaneously process 12 leads of ECG signals. By
      integrating the fabric electrodes into a T-shirt, the wearable system would
      provide a comfortable and convenient user interface for ECG recording. For
      comparison, the proposed fabric electrode and the gelled traditional metal
      electrodes were used to collect ECG signals on a subject, respectively. The
      approximate entropy (ApEn) of ECG signals from both types of electrodes were
      calculated. The experimental results show that the fabric electrodes could
      achieve similar performance as the gelled metal electrodes. This preliminary work
      has demonstrated that the developed ECG system with fabric electrodes could be
      utilized for wearable health management and telemedicine applications.

PMID- 29060883
TI  - A wearable hand gesture recognition device based on acoustic measurements at
      wrist.
AB  - This paper investigates hand gesture recognition from acoustic measurements at
      wrist for the development of a low-cost wearable human-computer interaction (HCI)
      device. A prototype with 5 microphone sensors on human wrist is benchmarked in
      hand gesture recognition performance by identifying 36 gestures in American Sign
      Language (ASL). Three subjects were recruited to perform over 20 trials for each
      set of hand gestures, including 26 ASL alphabets and 10 ASL numbers. Ten features
      were extracted from the signal recorded by each sensor. Support Vector Machine
      (SVM), Decision Tree (DT), K-Nearest Neighbors (kNN), and Linear Discriminant
      Analysis (LDA) were compared in classification performance. Among which, LDA
      offered the highest average classification accuracy above 80%. Based on these
      preliminary results, our proposed technique has exhibited a promising means for
      developing a low-cost HCI.

PMID- 29060884
TI  - Novel force-sensing system for minimally invasive surgical instruments.
AB  - Mastering proper force manipulation in minimally invasive surgery can take many
      years. Improper force control can lead to necrosis, infection, and scarring. This
      paper describes a novel system to measure, log, and display external forces at
      the distal end of minimally invasive surgical instruments in real-time. The
      system, comprising of a Force- Sensing Sleeve, Bluetooth electronics module, and
      an Android mobile application. A sensorized 5 mm minimally invasive surgical
      needle holder was evaluated for bending force accuracy, linearity, and
      repeatability in six directions. The results showed that the system responded
      linearly to forces at the tool-tip independent of direction with an RMS error of
      0.088 N. Repeatability was affected by system noise potentially arising from
      temperature drift and thermal noise. Future work will include characterization of
      communication performance for force feedback in surgical training and assessment.

PMID- 29060885
TI  - Office activity classification using first-reflection ultrasonic echolocation.
AB  - Excessive sedentary time poses considerable health risks for individuals
      predominately engaged in desk-bound work. To empower interventions aimed at
      addressing this problem, reliable technologies for continuous activity monitoring
      within an office environment are required. As an alternative to existing
      solutions, we propose the Echolocation-based Activity Detector, a contactless
      sensor array of four first-reflection ultrasonic distance sensors. The research
      described herein demonstrates the capacity of the sensor to distinguish between
      common activities performed at a workstation within an office environment,
      including sedentary sitting, typing, writing, and standing. Cubic support vector
      machine classifiers are developed using dispersion-related features computed from
      the time-series array outputs. Average classification accuracy for sedentary
      activities exceeds 85%, while classification accuracy for the entire activity set
      exceeds 80% for a controlled experiment conducted with six participants.

PMID- 29060886
TI  - A wearable ultrasonic sensor network for analysis of bilateral gait symmetry.
AB  - Analysis of bilateral gait symmetry and coordination is important in
      rehabilitation after lower-extremity trauma, prosthesis and neurovascular
      diseases. Moreover, it can act as a precursor of freezing of gait in Parkinson's
      disease. Current methods for gait symmetry analysis include Opto-electronic
      systems using multiple high-speed cameras, instrumented platforms etc. which are
      complex and costly. We propose a low-cost, wearable ultrasonic sensor network
      using readily available components, which is easy to use, portable and does not
      require complex calibration procedures. The system was tested on five healthy
      subjects and the results were compared with Motion Capture system. The
      experimental results show that the proposed system can be used to assess the
      human gait symmetry in a convenient and homely setup.

PMID- 29060887
TI  - Monitoring smoking behaviour using a wearable acoustic sensor.
AB  - Smoking is a cause of multiple health problems resulting in diseases which can
      also be fatal. It is well known that smoking has long-term impact on the health
      of an individual as well. While a number of studies have looked at the impact of
      smoking on health and its economic impacts, most of these rely on input from
      smokers in the form of questionnaires and surveys. Long-term monitoring of
      smoking habits and behaviour is thus not possible because of the lack of means to
      do so. This paper proposes the use of a wearable device to monitor breathing
      signals of subjects. It is shown that the acoustic properties of a smoking breath
      are different from a non-smoking breath. To encapsulate these differences,
      several features from a breath segment are extracted and used with a simple
      classifier to automatically identify smoking breaths. The proposed algorithm
      detected smoking and non-smoking breaths with average accuracy of 66% and 99%
      respectively.

PMID- 29060888
TI  - Propofol-induced sedation diminishes the strength of frontal-parietal-occipital
      EEG network.
AB  - The level of conscious experience can be effectively and reversibly altered by
      the administration of sedative agents. Several studies attempted to explore the
      variations in frontal-parietal network during propofol-induced sedation. However,
      contradictory outcomes warrant further investigations. In this study, we
      implemented the Neural Gas algorithm-based delay symbolic transfer entropy (NG
      dSTE) for investigation of frontal-parietal-occipital (F-P-O) network using scalp
      EEG signals recorded during altered levels of consciousness. Our results show
      significant disruption of the F-P-O network during mild and moderate levels of
      propofol sedation. In particular, the interaction between frontal and parietal
      occipital region is highly disturbed. Moreover, we found measurable effect of
      sedation on local interactions in the frontal network whereas parietal-occipital
      network experienced least variations. The results support the conclusion that the
      connectivity based features can be utilized as reliable biomarker for assessment
      of sedation levels effectively.

PMID- 29060889
TI  - Single-trial detection of event-related fields in MEG from the presentation of
      happy faces: Results of the Biomag 2016 data challenge.
AB  - The recognition of brain evoked responses at the single-trial level is a
      challenging task. Typical non-invasive brain-computer interfaces based on event
      related brain responses use eletroencephalograhy. In this study, we consider
      brain signals recorded with magnetoencephalography (MEG), and we expect to take
      advantage of the high spatial and temporal resolution for the detection of
      targets in a series of images. This study was used for the data analysis
      competition held in the 20th International Conference on Biomagnetism (Biomag)
      2016, wherein the goal was to provide a method for single-trial detection of even
      related fields corresponding to the presentation of happy faces during the rapid
      presentation of images of faces with six different facial expressions (anger,
      disgust, fear, neutrality, sadness, and happiness). The datasets correspond to
      204 gradiometers signals obtained from four participants. The best method is
      based on the combination of several approaches, and mainly based on Riemannian
      geometry, and it provided an area under the ROC curve of 0.956+/-0.043. The
      results show that a high recognition rate of facial expressions can be obtained
      at the signal-trial level using advanced signal processing and machine learning
      methodologies.

PMID- 29060890
TI  - Emergence of metastable dynamics in functional brain organization via spontaneous
      fMRI signal and whole-brain computational modeling.
AB  - Little is known about the mechanisms underlying the resting-state brain
      organization. This study investigated how metastability, defined as the standard
      deviation of synchrony described by the Kuramoto order parameter, arises from the
      structural connectome and relates to empirical measures of metastability in
      resting-state brain networks. We tested whether spontaneous fMRI brain activity
      in the functional organization of the human brain operates in a metastable state.
      We compared between empirical metastability defined in four major resting-state
      brain networks - auditory network, default mode network, left and right executive
      control networks - and simulated metastability derived from the Kuramoto model
      constrained by the empirical anatomical connectivity. Our results show that
      maximal metastability within resting-state brain networks arises from the model
      with different coupling strengths. Empirical metastability corresponds to a
      dynamical region where the simulated metastability is maximized. The emergence of
      metastable dynamics observed in empirical resting-state functional networks
      around the region of maximal metastability suggests that such a dynamical regime
      in the brain may drive the resting state of the brain. Our study may provide a
      mechanistic explanation of the origin of functional organization of the brain,
      and may help our understanding of the mechanistic causes of disease.

PMID- 29060891
TI  - Why build an integrated EEG-NIRS? About the advantages of hybrid bio-acquisition
      hardware.
AB  - OBJECTIVE: In medical applications, neuroscience and brain-computer interface
      research, bimodal acquisition of brain activity using Electroencephalography
      (EEG) and functional Near Infrared Spectroscopy (fNIRS) is at the moment achieved
      by combining separate commercial devices. We have investigated quantitatively
      whether dedicated hybrid systems exhibit more advantageous properties. METHODS:
      We studied intermodality electrical crosstalk and timing jitter in two separate
      and one hybrid EEG-NIRS acquisition device. RESULTS: Analysis revealed
      significantly higher impact of electrical NIRS current crosstalk into the EEG
      inputs and timing jitters between EEG-NIRS markers in separate devices compared
      to the hybrid system. CONCLUSION: The results support hybrid acquisition systems
      to be advantageous in setups that require high performance in timing and signal
      quality.

PMID- 29060892
TI  - Sensorimotor network parcellation for pre-surgical patients using low-pass
      filtered fMRI.
AB  - Pre-surgical mapping of sensorimotor and language functions is crucial to reduce
      neurological deficits in epilepsy and tumor resection surgery. As non-invasive
      mapping, both resting-state and task-evoked functional MRI has been explored in
      pre-surgical mapping. In lack of standardized test paradigm, the reliability of
      fMRI mapping is still a concern for clinical use. In this study, to improve the
      reliability of fMRI based mapping, task fMRI data from all available task
      paradigms (motor movement, word repeating and picture naming) were low-pass
      filtered in the band of resting-state fMRI (0.01-0.08Hz) and concatenated to get
      more time points. With K-means clustering, it was shown that the sensorimotor
      network could be reliably parcellated into hand and tongue sub-regions. The
      resulted parcellations were further verified with invasive ECoG and ECS mapping.
      Both the accuracy and specificity were better than using the motor-task fMRI
      only. Especially, for those patients who failed in task fMRI mapping, our method
      was able to provide accurate mapping as well. Our results also indicate that
      cortical sensorimotor network pattern is intrinsic and always present during
      various tasks, which supports the physiological link between the spontaneous and
      the task-evoked BOLD signals.

PMID- 29060893
TI  - An eye tracking index for the salience estimation in visual stimuli.
AB  - Every day we face visual stimuli able to catch our attention, but this aspect
      becomes crucial if the visual material has the purpose to spread a message aimed
      at engaging the observer. In this framework, a worthy aspect is how to measure
      the "visual engagement" produced by visual stimuli exposure. To this purpose, in
      the present study, employing the eye tracking technique, an index of visual
      attention (VA) has been proposed, and applied to pictures belonging to
      antismoking public service announcements, so to investigate the saliency of
      health-promoting messages in a young sample. The VA index is a non-dimensional
      index, defined as the ratio between the percentage of the total time spent
      fixating an area of interest (AOI) weighted on the total time the picture is
      showed on the screen, and the percentage of the area occupied by the AOI weighted
      on the total dimension of the picture. It could be predicted that AOI reporting
      higher VA values will be the ones having more saliency. Three antismoking Public
      Service Announcements (PSAs) images have been selected for the study and for each
      of them were identified: i) "picture" (such as a young man with a sarcastic
      expression depicted while smoking a cigarette, or the image of a lady who
      underwent a tracheotomy) and ii) "writing" (text of the antismoking message)
      AOIs. Main results of the analysis revealed that writing AOIs obtained
      statistically significant higher VA values than visual AOIs (p=0.03), but these
      held true only for an ineffective PSA, probably because the text was not
      perceived as pertinent with the surrounding image. On the other hand, an
      effective PSA obtained higher VA values in response to visual than writing AOIs
      observation (p=0.02). The VA index appears therefore to represent a useful tool
      to measure the saliency of visual stimuli elements.

PMID- 29060895
TI  - Manipulating the fidelity of lower extremity visual feedback to identify obstacle
      negotiation strategies in immersive virtual reality.
AB  - The ability to successfully navigate obstacles in our environment requires
      integration of visual information about the environment with estimates of our
      body's state. Previous studies have used partial occlusion of the visual field to
      explore how information about the body and impending obstacles are integrated to
      mediate a successful clearance strategy. However, because these manipulations
      often remove information about both the body and obstacle, it remains to be seen
      how information about the lower extremities alone is utilized during obstacle
      crossing. Here, we used an immersive virtual reality (VR) interface to explore
      how visual feedback of the lower extremities influences obstacle crossing
      performance. Participants wore a head-mounted display while walking on treadmill
      and were instructed to step over obstacles in a virtual corridor in four
      different feedback trials. The trials involved: (1) No visual feedback of the
      lower extremities, (2) an endpoint-only model, (3) a link-segment model, and (4)
      a volumetric multi-segment model. We found that the volumetric model improved
      success rate, placed their trailing foot before crossing and leading foot after
      crossing more consistently, and placed their leading foot closer to the obstacle
      after crossing compared to no model. This knowledge is critical for the design of
      obstacle negotiation tasks in immersive virtual environments as it may provide
      information about the fidelity necessary to reproduce ecologically valid practice
      environments.

PMID- 29060894
TI  - The external force associated with callus formation under the first metatarsal
      head is reduced by wearing rocker sole shoes.
AB  - INTRODUCTION: Callus is one of the main causes of diabetic foot ulcers.
      Therefore, preventing callus formation is very important. In a previous study, it
      was clarified that callus formation under the first metatarsal head (MTH) is
      associated with high shear stress time integral/pressure time integral (SPR-i).
      another study, it was clarified that rocker sole shoes are effective in reducing
      peak pressure under the first MTH. Therefore, we hypothesized that rocker sole
      shoes reduce SPR-i under the first MTH. This study aimed to clarify the effect of
      rocker sole shoes for external forces and leg motions in comparison with that of
      the normal sole shoes. METHODS: In-shoe external forces and leg motions were
      measured during walking wearing the normal sole shoes or the rocker sole shoes in
      healthy participants. As the external forces, the peak plantar pressure (PP),
      pressure time integral (PI), peak shear stress (PSS), and shear stress integral
      (SSI) of each gait cycle were calculated. Additionally, shear stress-pressure
      ratios (SPR) were calculated by dividing shear stress by pressure; concretely,
      peak values (SPR-p) and time integral values (SPR-i). As the leg motion, hip and
      knee joint motions were analyzed for the axis of flexion- extension. Three axes
      of ankle joint motion (inversion-eversion, plantar flexion-dorsiflexion, and
      adduction-abduction) were analyzed. RESULTS AND DISCUSSION: Six participants
      attended, and twelve feet were analyzed. When wearing the rocker sole shoes, the
      SPR-i under the first MTH was significantly smaller than when wearing the normal
      sole shoes. The SPR-i higher than 0.60 is associated with callus formation under
      the first MTH. In three of five feet with callus, SPR-i exceeded 0.60 in the
      normal sole shoes. The SPR-i of all three feet became smaller than 0.60 when
      wearing the rocker sole shoes. Although the knee (flexion-extension) and ankle
      (plantar flexion-dorsiflexion) joint motion became smaller when wearing the
      rocker sole shoes, there was no significant difference in walking speed. It is
      considered that propulsion was maintained by the push-off support provided by
      rocker sole shoes. CONCLUSION: It was suggested that rocker sole shoes are
      effective preventing callus formation under the first MTH.

PMID- 29060896
TI  - Prediction of microsleeps using pairwise joint entropy and mutual information
      between EEG channels.
AB  - Microsleeps are involuntary and brief instances of complete loss of
      responsiveness, typically of 0.5-15 s duration. They adversely affect performance
      in extended attention-driven jobs and can be fatal. Our aim was to predict
      microsleeps from 16 channel EEG signals. Two information theoretic concepts -
      pairwise joint entropy and mutual information - were independently used to
      continuously extract features from EEG signals. k-nearest neighbor (kNN) with k =
      3 was used to calculate both joint entropy and mutual information. Highly
      correlated features were discarded and the rest were ranked using Fisher score
      followed by an average of 3-fold cross-validation area under the curve of the
      receiver operating characteristic (AUCROC). Leave-one-out method (LOOM) was
      performed to test the performance of microsleep prediction system on independent
      data. The best prediction for 0.25 s ahead was AUCROC, sensitivity, precision,
      geometric mean (GM), and phi of 0.93, 0.68, 0.33, 0.75, and 0.38 respectively
      with joint entropy using single linear discriminant analysis (LDA) classifier.

PMID- 29060897
TI  - Ankle-foot orthosis using elastomer-embedded flexible joint.
AB  - We proposed a new ankle-foot orthosis using elastomer-embedded flexible joints
      (EEFJ), composed of C-shaped springs and 3D-printed circular elastomer. This
      orthosis was designed to reduce burden on the tibialis anterior muscle (TA) and
      to achieve clearance between the tip of the toe and the ground. Strength testing,
      and gait analysis were conducted for the orthosis. According to the results of
      strength testing, the combination of the C-spring with 0.3 mm and 0.5 mm
      thickness and the elastomer with 30% and 60% filling density performs a
      supporting torque of 0.7-2.3 Nm to plantarflexion. In contrast, torques in the
      other directions were relatively small. According to the results of gait
      experiments in seven healthy young subjects, the proposed orthosis successfully
      reduced the TA activation on initial contact and in the swing phase, and range of
      motion on initial contact.

PMID- 29060898
TI  - A modified D-max method to estimate heart rate at a ventilatory threshold during
      an incremental exercise test.
AB  - The purpose of this study was to design a modified D-max method to determine
      heart rate at a ventilatory threshold (HRVT) and to investigate whether this
      method would be valid during incremental exercise tests. The HRVT was estimated
      from a new parameter defined as HR at the maximal difference point between
      linearly- and quadratically approximated HR trends (modified D-max method). HR
      and ventilatory gas data for 105 subjects (53 males and 52 females; 38.26 +/-
      12.06 years; 166.62 +/- 8.21 cm; 65.31 +/- 11.10 kg) were simultaneously
      collected during an incremental treadmill test to evaluate the validity of the
      modified D-max method. Reference HRVTs were manually identified from the
      ventilatory gas data by an experienced sports physiologist and compared with
      those estimated by the HR parameter. A strong positive correlation (r = 0.71, p
      <; 0.01) and a low HR difference of 9.94 +/- 7.10 bpm between the reference and
      estimated HRVTs were obtained. The results indicate that the modified D-max
      method outperforms the conventional D-max method (r = 0.53, p <; 0.01), the three
      piece linear regression lines method (r = 0.42, p <; 0.01), and the parallel
      straight line slope method (r = 0.57, p <; 0.01). Furthermore, the modified D-max
      method improves the predictive accuracy of HRVTs by combining its result with
      subject's age. The combined parameters have a strong positive correlation with
      the reference HRVTs (r = 0.74, p <; 0.01) and a lower HR difference of 9.40 +/-
      6.91 bpm. The results suggest that the modified D-max method is highly applicable
      to predicting HRVTs during incremental exercise tests and also improves HRVT
      detection accuracy by combining its result with the subject's age.

PMID- 29060899
TI  - Unified Health Gamification can significantly improve well-being in corporate
      environments.
AB  - There is a multitude of mHealth applications that aim to solve societal health
      problems by stimulating specific types of physical activities via gamification.
      However, physical health activities cover just one of the three World Health
      Organization (WHO) dimensions of health. This paper introduces the novel notion
      of Unified Health Gamification (UHG), which covers besides physical health also
      social and cognitive health and well-being. Instead of rewarding activities in
      the three WHO dimensions using different mHealth competitions, UHG combines the
      scores for such activities on unified leaderboards and lets people interact in
      social circles beyond personal interests. This approach is promising in corporate
      environments since UHG can connect the employees with intrinsic motivation for
      physical health with those who have quite different interests. In order to
      evaluate this approach, we realized an app prototype and we evaluated it in two
      corporate pilot studies. In total, eighteen pilot users participated voluntarily
      for six weeks. Half of the participants were recruited from an occupational
      health setting and the other half from a treatment setting. Our results suggest
      that the UHG principles are worth more investigation: various positive health
      effects were found based on a validated survey. The mean mental health improved
      significantly at one pilot location and at the level of individual pilot
      participants, multiple other effects were found to be significant: among others,
      significant mental health improvements were found for 28% of the participants.
      Most participants intended to use the app beyond the pilot, especially if it
      would be further developed.

PMID- 29060900
TI  - Automatic diagnosis of tuberculosis disease based on Plasmonic ELISA and color
      based image classification.
AB  - Tuberculosis (TB) remains one of the most devastating infectious diseases and its
      treatment efficiency is majorly influenced by the stage at which infection with
      the TB bacterium is diagnosed. The available methods for TB diagnosis are either
      time consuming, costly or not efficient. This study employs a signal generation
      mechanism for biosensing, known as Plasmonic ELISA, and computational
      intelligence to facilitate automatic diagnosis of TB. Plasmonic ELISA enables the
      detection of a few molecules of analyte by the incorporation of smart
      nanomaterials for better sensitivity of the developed detection system. The
      computational system uses k-means clustering and thresholding for image
      segmentation. This paper presents the results of the classification performance
      of the Plasmonic ELISA imaging data by using various types of classifiers. The
      five-fold cross-validation results show high accuracy rate (>97%) in classifying
      TB images using the entire data set. Future work will focus on developing an
      intelligent mobile-enabled expert system to diagnose TB in real-time. The
      intelligent system will be clinically validated and tested in collaboration with
      healthcare providers in Malaysia.

PMID- 29060901
TI  - Novel features from autocorrelation and spectrum to classify Phonocardiogram
      quality.
AB  - Phonocardiogram (PCG) or auscultation via a stethoscope forms the basis of
      preliminary medical screening. But PCG recorded in an uncontrolled environment is
      inherently noisy. In this paper we have derived novel features from the spectral
      domain and autocorrelation waveforms. These are used to identify the quality of a
      PCG recording and accepting only diagnosable quality recordings for further
      analysis. These features proved to be robust irrespective of variations in
      devices and in data collection protocols employed to ensure consistent data
      quality. A freely available, large, diverse, medical-grade PCG dataset was used
      for creating the training models. Results show that the proposed methodology
      yields an accuracy score of ~75% on our in-house PCG dataset, collected using a
      low-cost smartphone-based digital stethoscope.

PMID- 29060902
TI  - Detection of chewing motion in the elderly using a glasses mounted accelerometer
      in a real-life environment.
AB  - This paper describes a method of detecting an elderly person's chewing motion
      using a glasses mounted accelerometer. A real-life dataset was collected from 13
      elderly adults, aged 65 or older, during meal times in a care facility. A
      supervised classifier is used to automatically distinguish between epochs of
      chewing and non-chewing activity. Results are compared to a lab dataset of 5
      young to middle-aged adults captured in previous work. K-Nearest Neighbor, Random
      Forest and Support Vector Machine classifiers are evaluated. All are able to
      achieve similar performance, with the Support Vector Machine performing the best
      with an F1-score of 0.73.

PMID- 29060903
TI  - Development of evaluation methods for the approval and review of Intense pulsed
      light (IPL).
AB  - This Intense pulsed light (IPL) is skin therapy medical device to remove
      infection and lesion. The market size of IPL has increased because of increasing
      device users such as doctors, nurses, engineers, patients. Thus, the number of
      IPL approvals by Ministry of Food and Drug Safety (MFDS) has increased. However,
      since there are no standard and guideline for evaluation of IPL performance and
      safety, it is need to develop the evaluation method of IPL performance and safety
      for petitioners and examiners who are having difficulties in approval and review.
      In this study, the criteria and methods for scientificevaluation of safety and
      performance of IPL are proposed tosupport approval and review, and it is expected
      to enhance theinternational competitiveness of domestic medical deviceindustry
      and patient safety.To develop the evaluation methods of IPL, first, the types
      andinformation of IPL have been collected and analyzed, andrelative international
      and domestic standard and FDA guidancehave been studied. Second, drawn test
      items, criteria andmethods were verified at medical device testing
      institute.Finally, the guideline for evaluation of IPL performance andsafety was
      reviewed through a consultative body composed ofacademic, industrial, institute,
      and government experts.

PMID- 29060904
TI  - Tapered fiber optic applicator for laser ablation: Theoretical and experimental
      assessment of thermal effects on ex vivo model.
AB  - Laser Ablation (LA) is a minimally invasive technique for tumor removal. The
      laser light is guided into the target tissue by a fiber optic applicator; thus
      the physical features of the applicator tip strongly influence size and shape of
      the tissue lesion. This study aims to verify the geometry of the lesion achieved
      by a tapered-tip applicator, and to investigate the percentage of thermally
      damaged cells induced by the tapered-tip fiber optic applicator. A theoretical
      model was implemented to simulate: i) the distribution of laser light fluence
      rate in the tissue through Monte Carlo method, ii) the induced temperature
      distribution, by means of the Bio Heat Equation, iii) the tissue injury, by
      Arrhenius integral. The results obtained by the implementation of the theoretical
      model were experimentally assessed. Ex vivo porcine liver underwent LA with
      tapered-tip applicator, at different laser settings (laser power of 1 W and 1.7
      W, deposited energy equal to 330 J and 500 J, respectively). Almost spherical
      volume lesions were produced. The thermal damage was assessed by measuring the
      diameter of the circular-shaped lesion. The comparison between experimental
      results and theoretical prediction shows that the thermal damage discriminated by
      visual inspection always corresponds to a percentage of damaged cells of 96%. A
      tapered-tip applicator allows obtaining localized and reproducible damage close
      to spherical shape, whose diameter is related to the laser settings, and the
      simple theoretical model described is suitable to predict the effects, in terms
      of thermal damage, on ex vivo liver. Further trials should be addressed to adapt
      the model also on in vivo tissue, aiming to develop a tool useful to support the
      physician in clinical application of LA.

PMID- 29060905
TI  - Effects of Nd:YAG laser for the controlled and localized treatment of early
      gastrointestinal tumors: Preliminary in vivo study.
AB  - Endoscopic submucosal dissection (ESD) is a minimally invasive technique allowing
      for the removal of early gastrointestinal (GI) tumors, widely considered as a
      valid alternative to conventional surgery. However, ESD is technically demanding,
      and potentially severe complications, such as bleeding and perforation, may
      occur. Energy-based techniques (e.g., radiofrequency ablation) might offer a
      potential alternative to ESD. However, their use mandates the ability to predict
      the damage induced and to identify a "signature" of the complete ablation,
      without the need for a physical specimen. Ideally, an energy-based procedure
      should be tunable in order to limit the ablation to the superficial layers,
      namely mucosa (M) and submucosa (SM), without injuring the muscularis propria
      (MP), thereby minimizing GI perforation. This experimental study aims to
      investigate thermal damage induced by Nd:YAG laser on the gastric wall, at
      different laser settings such as power (P) and time (t). Laser ablation was
      performed on the stomach wall of 6 Wistar rats. Two powers (2.5W and 1.0W) and 3
      exposure times (12s, 6s and 2s) were tested, for a total of 30 ablations.
      Histological analysis allowed to assess thermal damage, in terms of damage depth
      (DD) and identification of involved layers. The ratio (R) between DD and the
      total depth (TD) of target layers (M+SM) was used as an index to evaluate the
      effectiveness of laser settings. At P=2.5W, MP was damaged (R>1) in the majority
      of cases (11/15). At P=1.0W, MP was preserved in all tests (R<;1), and rarely
      (4/15) did the damage reach the whole SM (R=1). Histopathological analysis
      evidenced that tissue damage was strongly related to the variable tissue
      thickness. These preliminary results seem to support the fact that endoscopic
      tunable laser ablation is feasible with a consistent damage/power correlation.
      Further tests are required to optimize the settings for applications on early GI
      tumors.

PMID- 29060907
TI  - A novel sensor for measuring temperature profile during the thermoablation.
AB  - A novel approach for monitoring a temperature distribution inside a tissue during
      thermoablation is presented in the paper. A thermal profile is measured using a
      set of serially connected thermistors each bypassed by a capacitor. This
      technique allows a two-wire and simultaneous multi-point measurements using a
      multi-frequency measurement of electrical impedance. It is shown that application
      signals of appropriately selected frequency allows simultaneous measurement of
      temperature at five distinct points. This technique can be utilized in the
      assisting of a thermoablation process, and in other applications based on
      resistive or capacitive sensors.

PMID- 29060906
TI  - Surface modifications of human tooth using Nd:YAG laser for dental applications.
AB  - Ablation using Nd:YAG laser has potential in resulting a rough effect on tooth
      surfaces. The objective of this study is to perform a comparative evaluation of
      the roughness structure of enamel using the Cynosure Cynergy Nd:YAG laser and 37%
      phosphoric acid. The results obtained for laser-etched with a pulse width of
      300ms show roughed and porous surface with greater depth. Both show remarkable
      graininess on the surface and fewer indentations. Comparison of the elemental
      compositions demonstrated that calcium has higher composition when exposed to
      laser-etch compared to acid-etch. The atomic percentages of calcium in sample A
      for acid-etched and laser-etched are 5.08 and 9.61, respectively. While acid
      etched and laser-etched for sample B are 3.98 and 12.84, respectively. Other
      elements are not profoundly affected by the technique used in this study.
      However, carbon and oxygen show inconsistent results for both of the samples.
      Thus, Nd:YAG laser provides significant effects on the tooth surface but does not
      primarily modify the element compositions of the tooth. Therefore, Nd:YAG laser
      can potentially be implemented for etching procedure as a replacement of acid
      etching technique.

PMID- 29060908
TI  - Preliminary study on Low Intensity Focused Ultrasound system For neuromodulation.
AB  - A Prototype Low Intensity Focused Ultrasound for brain targeting in a rat model
      was developed and tested. Accordingly, were evaluated low intensity focused
      ultrasound accuracy and performance. By utilizing the Rat Brain, no death or
      necrosis of cells, it was confirmed that the energy is gathered at that targeted.

PMID- 29060909
TI  - Differential effects of physical and psychological stressors on electrodermal
      activity.
AB  - Stress being labelled by WHO as "the health epidemic of 21st century" need to be
      treated as a clarion call for devising strategies that aim at its early
      detection, for the reason that stress is the cause as well as the catalyst for
      several chronic human health disorders. The work reported here in is a
      progression towards the development of a stress detection system based on the
      electrodermal activity (EDA) in humans, which can further be incorporated into a
      wearable vital signs monitor. The utility of EDA as a potential physiological
      measure for classifying physical and psychological stressors is analyzed in this
      paper. A group of 12 subjects (8 males and 4 females, age: 25.4 +/- 3.1 years,
      mean +/- SD) volunteered to participate in a laboratory stress task that included
      a psychological stressor close to real life work stress scenario and a physical
      stressor. The capability of stressors to elicit persistent stress response was
      validated by assessing variations in salivary cortisol levels. EDA was monitored
      throughout the experiment sessions as a measure of sympathetic activation in
      subjects. Six classification models were investigated concerning their usability
      to distinguish physical and psychological stressors based on EDA. A maximum
      accuracy of 95.1% was achieved using linear discriminat analysis (LDA) based
      classifier which imply that EDA is indeed a potential discriminate measure to
      classify physical and psychological stress responses. Furthermore, the best
      feature combination for maximum classification accuracy was also determined.

PMID- 29060910
TI  - An autonomous medical monitoring system: Validation on arrhythmia detection.
AB  - In this paper, we present a generic platform for autonomous medical monitoring
      and diagnostics. We validated the platform in the context of arrhythmia detection
      with publicly available databases. The big advantage of this platform is its
      capacity to deal with various types of physiological signals. Many pre-processing
      steps are performed to bring the input information into a uniform state that will
      be explored by a machine learning algorithm. Since this block plays a crucial
      role in the entire processing pipeline, three different methods were evaluated
      for detection and classification of anomalies. The results presented in this work
      are validated on cardiac beats, where the highest accuracy was obtained on the
      classification of normal beats (94%). On the other hand, atrial fibrillation and
      premature ventricular contraction beats were classified with an accuracy of 78%.

PMID- 29060911
TI  - Virtual Proprioception for eccentric training.
AB  - Wireless inertial sensors enable quantified feedback, which can be applied to
      evaluate the efficacy of therapy and rehabilitation. In particular eccentric
      training promotes a beneficial rehabilitation and strength training strategy.
      Virtual Proprioception for eccentric training applies real-time feedback from a
      wireless gyroscope platform enabled through a software application for a
      smartphone. Virtual Proprioception for eccentric training is applied to the
      eccentric phase of a biceps brachii strength training and contrasted to a biceps
      brachii strength training scenario without feedback. During the operation of
      Virtual Proprioception for eccentric training the intent is to not exceed a
      prescribed gyroscope signal threshold based on the real-time presentation of the
      gyroscope signal, in order to promote the eccentric aspect of the strength
      training endeavor. The experimental trial data is transmitted wireless through
      connectivity to the Internet as an email attachment for remote post-processing. A
      feature set is derived from the gyroscope signal for machine learning
      classification of the two scenarios of Virtual Proprioception real-time feedback
      for eccentric training and eccentric training without feedback. Considerable
      classification accuracy is achieved through the application of a multilayer
      perceptron neural network for distinguishing between the Virtual Proprioception
      real-time feedback for eccentric training and eccentric training without
      feedback.

PMID- 29060912
TI  - Motion-oriented noisy physiological signal refining using embedded sensing
      platforms.
AB  - Recent improvements in data learning techniques have catalyzed the development of
      various clinical learning systems. However, for clinical applications, training
      from noisy data can cause significant misleading results, directly leading to
      potentially dangerous clinical decisions. Given its importance, this work targets
      to present a preliminary effort to identify corrupted vital sign data by
      analyzing the patient motions on hospital beds. Specifically, we design an
      embedded sensor-based motion detection platform to capture and categorize
      different noise-causing motion on intensive care unit beds through a pre
      deployment study at the Ajou University Hospital. We design light-weight and low
      resource demanding software for motion sensor data processing and evaluate its
      performance from real-patient traces collected at the ICU. Evaluation results
      using a ~200 minute data set show that our system detects and classifies patient
      motion states with 76% accuracy and well-identifies vital sign time-series
      regions affected by motion noise.

PMID- 29060913
TI  - Detection of generalized tonic-clonic seizures using short length accelerometry
      signal.
AB  - Epileptic seizures are characterized by the excessive and abrupt electrical
      discharge in the brain. This asynchronous firing of neurons causes unprovoked
      convulsions which can be a cause of sudden unexpected death in epilepsy (SUDEP).
      Remote monitoring of epileptic patients can help prevent SUDEP. Systems based on
      wearable accelerometer sensors have shown to be effective in ambulatory
      monitoring of epileptic patients. However, these systems have a trade-off between
      seizure duration and the false alarm rate (FAR). The FAR of the system decreases
      as we increase the seizure duration. Further, multiple sensors are used in
      conjugation to improve the overall performance of the detection system. In this
      study, we propose a system based on single wrist-worn accelerometer sensor
      capable of detecting seizures with short duration (>= 10s). Seizure detection was
      performed by employing machine learning approach such as kernelized support
      vector data description (SVDD). The proposed approach is validated on data
      collected from 12 patients, corresponding to approximately 966h of recording
      under video-telemetry unit. The algorithm resulted in a seizure detection
      sensitivity of 95.23% with a mean FAR of 0.72=24h.

PMID- 29060914
TI  - Three-wavelength method for the optical differentiation of methemoglobin and
      sulfhemoglobin in oxygenated blood.
AB  - Methemoglobinemia and sulfhemoglobinemia are rare, but potentially life
      threatening, diseases that refer to an abnormal amount of methemoglobin or
      sulfhemoglobin in the blood, respectively. Unfortunately, blood samples
      containing abnormal quantities of methemoglobin or sulfhemoglobin have similar
      spectral characteristics. This makes it difficult to optically differentiate them
      and, hence, difficult to diagnose a patient with either disease. However,
      performing treatments for one of the diseases without a correct diagnosis can
      introduce increased risk to the patient. In this paper, we propose a method for
      differentiating the presence of methemoglobin and sulfhemoglobin in blood, under
      several conditions, using reflectance values measured at three wavelengths. In
      order to validate our method, we perform in silico experiments considering
      various levels of methemoglobin and sulfhemoglobin. These experiments employ a
      cell-based light interaction model, known as CLBlood, which accounts for the
      orientation and distribution of red blood cells. We then discuss the reflectance
      curves produced by the experiments and evaluate the efficacy of our method. In
      particular, we consider various experimental conditions by modifying the flow
      rate, hemolysis level and incident light direction.

PMID- 29060915
TI  - Feature extraction techniques for low-power ambulatory wheeze detection
      wearables.
AB  - Presence of wheezes in breathing sounds has been associated with several
      respiratory and pulmonary diseases. In this paper we present a novel low
      complexity wheeze detection method based on frequency contour tracking for
      automatic wheeze detection. Two hardware friendly variants of the algorithm have
      also been proposed. Applying the proposed feature extraction algorithm we
      achieved very high classification accuracy (> 99%) at considerably low
      computational complexity (3*-6*) compared to earlier methods and the power
      consumption of the proposed method is shown to be significantly less (70*-100*)
      compared to 'record and transmit' strategy in wearable devices.

PMID- 29060916
TI  - Cough sound analysis for diagnosing croup in pediatric patients using
      biologically inspired features.
AB  - This paper aims to diagnose croup in children using cough sound signal
      classification. It proposes the use of a time-frequency image-based feature,
      referred as the cochleagram image feature (CIF). Unlike the conventional
      spectrogram image, the cochleagram utilizes a gammatone filter which models the
      frequency selectivity property of the human cochlea. This helps reveal more
      spectral information in the time-frequency image making it more useful for
      feature extraction. The cochleagram image is then divided into blocks and central
      moments are extracted as features. Classification is performed using logistic
      regression model (LRM) and support vector machine (SVM) on a comprehensive real
      world cough sound signal database containing 364 patients with various clinically
      diagnosed respiratory tract infections divided into croup and non-croup. The best
      results, sensitivity of 88.37% and specificity of 91.59%, are achieved using SVM
      classification on a combined feature set of CIF and the conventional mel
      frequency cepstral coefficients (MFCCs).

PMID- 29060917
TI  - A robust dataset-agnostic heart disease classifier from Phonocardiogram.
AB  - Automatic classification of normal and abnormal heart sounds is a popular area of
      research. However, building a robust algorithm unaffected by signal quality and
      patient demography is a challenge. In this paper we have analysed a wide list of
      Phonocardiogram (PCG) features in time and frequency domain along with
      morphological and statistical features to construct a robust and discriminative
      feature set for dataset-agnostic classification of normal and cardiac patients.
      The large and open access database, made available in Physionet 2016 challenge
      was used for feature selection, internal validation and creation of training
      models. A second dataset of 41 PCG segments, collected using our in-house smart
      phone based digital stethoscope from an Indian hospital was used for performance
      evaluation. Our proposed methodology yielded sensitivity and specificity scores
      of 0.76 and 0.75 respectively on the test dataset in classifying cardiovascular
      diseases. The methodology also outperformed three popular prior art approaches,
      when applied on the same dataset.

PMID- 29060918
TI  - Identification of chronic heart failure using linear and nonlinear analysis of
      heart sound.
AB  - Chronic heart failure (CHF) is a cardiac condition caused by various of cardiac
      diseases in the end stage. This paper employed the linear and nonlinear
      approaches to analyze the heart sound (HS) signals from the patients with CHF.
      The linear approaches include the time and frequency domain analysis. The
      nonlinear parameters include largest Lyapunov exponent, correlation dimension,
      sample entropy and the width of multifractal spectrum, which describe the chaos,
      fractal characteristics and complexity of the HS signals. Statistical test and
      receiver operating characteristic (ROC) curve analysis have been applied to the
      characteristic parameters extracted from the HS signals of the healthy subjects
      and CHF patients. The results show that the statistically significant differences
      of linear and nonlinear features between the healthy and CHF groups can be
      observed. Compared to the healthy people, the cardiac mechanical activity of the
      patients with CHF has a decreased chaotic characteristic, complexity and
      randomness, and it indicates the HS features could be the measure to distinguish
      the CHF patients from the healthy subjects. Hence, our study suggests the
      proposed features could be as supplementary indexes or efficient clues for the
      diagnosis of CHF.

PMID- 29060919
TI  - Evaluating the use of neural networks and acoustic measurements to identify
      laryngeal pathologies.
AB  - Nineteen acoustical measurements were related to 23 larynx conditions by
      artificial neural networks (ANNs) and principal component analysis. An exhaustive
      analysis (combining all possible sets of acoustical measurements as ANN inputs)
      showed a performance of 99.4% for accuracy and 90.3% for sensitivity and
      specificity in classifying voice signals into normal and non-normal larynx
      conditions. In the case of individual larynx condition identification, the
      general sensitivity drop significantly (6.4%), although some conditions were
      better identified (including "vocal nodules" and "cysts") then others, reaching
      99.8% of sensitivity. We also identified the acoustical measurements that
      produced the best classification results.

PMID- 29060920
TI  - Automated lung sound analysis for detecting pulmonary abnormalities.
AB  - Identification of pulmonary diseases comprises of accurate auscultation as well
      as elaborate and expensive pulmonary function tests. Prior arts have shown that
      pulmonary diseases lead to abnormal lung sounds such as wheezes and crackles.
      This paper introduces novel spectral and spectrogram features, which are further
      refined by Maximal Information Coefficient, leading to the classification of
      healthy and abnormal lung sounds. A balanced lung sound dataset, consisting of
      publicly available data and data collected with a low-cost in-house digital
      stethoscope are used. The performance of the classifier is validated over several
      randomly selected non-overlapping training and validation samples and tested on
      separate subjects for two separate test cases: (a) overlapping and (b) non
      overlapping data sources in training and testing. The results reveal that the
      proposed method sustains an accuracy of 80% even for non-overlapping data sources
      in training and testing.

PMID- 29060921
TI  - The use of electromyography and magnetic resonance imaging to evaluate a core
      strengthening exercise programme.
AB  - BACKGROUND: The question that was asked in the study was whether a training
      routine based on curl-up exercises with a load provided by body mass of the
      person increases local muscle strength or local muscle endurance. OBJECTIVE: The
      aim of this study was to evaluate the effect of 4 weeks training based on a small
      load and low movement velocity on electrical activity (EMG), cross-sectional area
      (CSA) of core stabilisers. METHODS: The EMG activity was measured in the rectus
      abdominis (RA), obliquus abdominis externus and erector spinae (ES) muscles. CSA
      of the muscles: RA, anterolateral abdominal, psoas major, quadratus lumborum, ES,
      and multifidus at the level of L3-L4 were measured too. RESULTS: The training
      increased the CSA and thickness in most of the muscles studied. Statistically
      significant correlation was found only for the ES circumference (left side) and
      EMG activity for the right side (r= 0.627, p= 0.022) and left side (r= 0.624, p=
      0.023). CONCLUSIONS: The training programme resulted in a increase in the number
      of curl-up repetitions revealing an endurance increase in abdominal muscles.
      Furthermore, there was a increase in the EMG activity of the RA. An increase of
      the CSA of all tested muscles showed an increase of muscle active force.

PMID- 29060922
TI  - Comparison of spinal sagittal parameters by time of day in a healthy working
      population: Do we bend during the day?
AB  - BACKGROUND: Prospective study. OBJECTIVE: To determine the change in spinal
      sagittal parameters which may occur throughout the day in healthy population.
      METHODS: Thirty-five healthy hospital employees were enrolled in the study. Two
      standing left lateral orthoroentgenograms were obtained at 8.00 a.m and at 6.00
      p.m. Six spinopelvic parameters were measured on the X-rays. Thereafter, the
      subjects were divided into two cohorts according to their BMI as low BMI and high
      BMI. RESULTS: Thirty-five subjects with a mean age of 25.97 +/- 8.21 were
      evaluated. No significant change was found between morning and evening
      measurements for any of the parameters. Direct relationship was shown between
      thoracic kyphosis (TK) and lumbar lordosis (LL), lumbar lordosis and sacral slope
      (SS), pelvic tilt (PT) and pelvic incidence (PI) minus lumbar lordosis, sagittal
      vertebral axis (SVA) and pelvic incidence minus lumbar lordosis. In addition an
      inverse relationship was found between sacral slope and pelvic tilt, sacral slope
      and pelvic incidence minus lumbar lordosis, thoracic kyphosis and pelvic
      incidence minus lumbar lordosis, sacral slope and pelvic tilt, sagittal vertebral
      axis and lumbar lordosis (p< 0.05). Sagittal vertebral axis were found to be
      higher in the high BMI group, and daily change was lower but the differences were
      not statistically significant. Only the change in pelvic tilt value was found to
      be statistically significant in low BMI group. CONCLUSION: Routine workload in a
      hospital environment does not cause significant change in the spinopelvic
      parameters throughout the day.

PMID- 29060923
TI  - Infiltration of gamma?delta T cells, IL-17+ T cells and FoxP3+ T cells in human
      breast cancer.
AB  - BACKGROUND: Tumor-infiltrating lymphocytes (TILs) have a strong prognostic value
      in various forms of cancers. These data often refer to use of the pan-T cell
      marker CD3, or the cytotoxic T lymphocyte marker CD8alpha. However, T cells are a
      heterogeneous group of cells with a wide array of effector mechanisms ranging
      from immunosuppression to cytotoxicity. OBJECTIVE: In this study we have
      investigated the prognostic effects of some unconventional T cell subtypes in
      breast cancer; gamma?delta T cells, IL-17+ T cells and FoxP3+ T cells (Tregs) in
      relation to the conventional CD3 and CD8alpha T cell markers. METHODS: This was
      done using immunohistochemistry on a human breast cancer tissue microarray
      consisting of 498 consecutive cases of primary breast cancer. RESULTS:
      Infiltration of gamma?delta T cells and T cell infiltration in general (CD3),
      correlated with a good prognosis, while Treg infiltration with a worse.
      Infiltration of gamma?delta T cells was associated with a significantly improved
      clinical outcome in all breast cancer subtypes except triple negative tumors.
      Only infiltration of either CD3+ or CD8alpha+ cells was independently associated
      with better prognosis for all breast cancer patients. CONCLUSIONS: This study
      sheds further light on the prognostic impact of various T cell subtypes in breast
      cancer.

PMID- 29060924
TI  - Identification of key genes in endometrioid endometrial adenocarcinoma via TCGA
      database.
AB  - BACKGROUND: Understanding the molecular mechanisms is important in development
      and therapy of endometrioid endometrial adenocarcinoma. OBJECTIVE: To identify
      key genes in endometrioid endometrial adenocarcinoma. METHODS: The data of mRNA,
      miRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA)
      database and differential analysis was performed. Then, bioinformatic analysis
      was used to explore the regulatory mechanisms of miRNA and DNA methylation on
      gene expression. The regulatory network between differentially expressed miRNAs
      and target genes was established. Finally, the quantitative RT-PCR was applied to
      validate the bioinformatics results. RESULTS: We obtained biological omics data
      of 381 patients with endometrioid endometrial adenocarcinoma from TCGA data
      portal. After data processing, up to 2068 DEGs and 69 differentially expressed
      miRNAs were identified. Prediction and correlation analysis revealed that 175
      DEGs that were not only the target genes but also negatively correlated with the
      screened differentially expressed miRNAs. After the integrated analysis of
      differentially methylated CpG islands and DEGs, 16 related genes were obtained.
      The quantitative RT-PCR results were roughly consistent with the bioinformatics
      analysis. CONCLUSIONS: The altered DEGs (ZEB1, ZEB2, TIMP2, TCF4, CYP1B1, PITX1,
      PITX2, ZNF154 and TSPYL5) may be involved in tumor differentiation of
      endometrioid endometrial adenocarcinoma and could be used as potential
      therapeutic targets for the disease.

PMID- 29060925
TI  - Breath based volatile organic compounds in the detection of breast, lung, and
      colorectal cancers: A systematic review.
AB  - BACKGROUND: Detecting volatile organic compounds (VOCs) could provide a rapid,
      noninvasive, and inexpensive screening tool for detecting cancer. OBJECTIVE: In
      this systematic review, we identified specific exhaled breath VOCs correlated
      with lung, colorectal, and breast cancer. METHODS: We identified relevant studies
      published in 2015 and 2016 by searching Pubmed and Web of Science. The protocol
      for this systematic review was registered in PROSPERO and the PRISMA guidelines
      were used in reporting. VOCs and performance data were extracted. RESULTS: Three
      hundred and thirty three records were identified and 43 papers were included in
      the review, of which 20 were review articles themselves. We identified 17 studies
      that listed the VOCs with at least a subset of statistics on detection cutoff
      levels, sensitivity, specificity, area under the receiver operating
      characteristic curve (AUC), and gradient. CONCLUSIONS: Breath analysis for cancer
      screening and early detection shows promise, because samples can be collected
      easily, safely, and frequently. While gas chromatography-mass spectrometry is
      considered the gold standard for identifying specific VOCs, breath analysis has
      moved into analyzing patterns of VOCs using a variety of different multiple
      sensor techniques, such as eNoses and nanomaterials. Further development of VOCs
      for early cancer detection requires clinical trials with standardized breath
      sampling methods.

PMID- 29060926
TI  - Programmed death-1 ligand-1 gene rs2890658 polymorphism associated with the risk
      of esophageal squamous cell carcinoma in smokers.
AB  - BACKGROUND: The most important anti-tumor immune response is mediated by T
      lymphocytes. The interaction of programmed death-1 ligand-1 (PD-L1) with its
      receptor provides an inhibitory signal in T lymphocytes activation and
      proliferation. OBJECTIVE: This study aimed to investigate whether polymorphisms
      of PD-L1 were associated with the risk and prognosis of esophageal squamous cell
      carcinoma (ESCC) in a high-incidence population from Northern China. METHODS: PD
      L1 rs2890658 A/C and rs4143815 C/G single nucleotide polymorphisms (SNPs) were
      genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method
      in 575 ESCC patients and 577 healthy controls. RESULTS: There was no significant
      difference in the genotype frequencies of these two SNPs between the ESCC
      patients and the healthy controls. However, for rs2890658 A/C SNP, compared with
      the C/C genotype, the A/C genotype increased the risk of ESCC for the smokers (OR
      = 1.513, 95% CI = 1.006-2.287). Among the 575 ESCC patients, the survival
      information of 202 ESCC patients was collected. Neither the rs2890658 A/C SNP nor
      the rs4143815 C/G SNP was associated with the survival of ESCC patients.
      CONCLUSIONS: PD-L1 rs2890658 A/C SNP might be used as risk marker of the
      susceptibility to ESCC for the Han nationality in a high-incidence population
      from Northern China.

PMID- 29060927
TI  - Long intergenic non-protein coding RNA 1006 used as a potential novel biomarker
      of gastric cancer.
AB  - BACKGROUND: Accumulating evidences have shown that long non-coding RNAs
      (lncRNAs), longer than 200 nucleotides in length, play a crucial role in cancer
      occurrence and development. However, the relationships between most lncRNAs and
      gastric carcinogenesis remain poorly understood. OBJECTIVE: To explore the
      diagnostic value of one typical lncRNA, long intergenic non-protein coding RNA
      1006 (LINC01006), in gastric cancer. METHODS: First, real-time quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine
      the expression levels of LINC01006 in various gastric tissues from gastric cancer
      patients, healthy controls, and gastric dysplasia. Next, the correlation between
      LINC01006 expression levels and clinicopathological features of patients with
      gastric cancer was assessed. Finally, the relative levels of LINC01006 in gastric
      cancer cell lines comparing to normal gastric epithelial cell line were analyzed.
      RESULTS: LINC01006 levels in cancer tissues were significantly lower than those
      in adjacent normal tissues (P< 0.001) and healthy control tissues (P< 0.001). Its
      expression was associated with age (P= 0.013), tumor location (P= 0.022), tumor
      size (P= 0.030), and venous invasion (P= 0.018). Moreover, expression of
      LINC01006 was downregulated in two gastric cancer cell lines, MGC-803 (P< 0.05)
      and AGS (P< 0.001) compared to normal gastric epithelial cell line GES-1.
      CONCLUSIONS: All the data implied that LINC01006 may be a novel biomarker for
      gastric cancer.

PMID- 29060928
TI  - Serum relaxin as a diagnostic and prognostic marker in patients with epithelial
      ovarian cancer.
AB  - BACKGROUND AND AIM: Relaxin is a short circulating peptide hormone. The aim of
      this study was to understand the role of relaxin in progression of epithelial
      ovarian cancer (EOC) and to assess its diagnostic and prognostic significance.
      METHODS: A total of 124 patients with EOC, 46 patients with benign ovarian
      diseases, and 50 healthy controls were recruited. Serum levels of relaxin were
      determined by ELISA method. The relationship between serum relaxin level and each
      of the clinicopathological parameters was analyzed using the chi2 test. Survival
      curves were plotted using the Kaplan-Meier method. The statistical difference in
      survival between the different groups was compared using the log-rank test.
      Survival correlation with the prognostic factors was further investigated by
      multivariate analysis using the Cox proportional hazards model with backward
      stepwise likelihood ratio. RESULTS: The results showed that serum relaxin level
      was significantly higher in patients with EOC than those with benign ovarian
      diseases and healthy controls (p< 0.01). Serum relaxin level was associated with
      FIGO stage, lymph node metastasis, tumor resectability, survival of the patients,
      chemotherapy and tumor recurrence (p< 0.05). Analysis using the Kaplan-meier
      method indicated that patients with high serum relaxin had significantly shorter
      overall survival time than those with low relaxin (p< 0.01). In a multivariate
      analysis along with clinical prognostic parameters, serum relaxin was identified
      as an independent adverse prognostic variable for survival. CONCLUSIONS: These
      results indicated that serum relaxin may be a clinically useful indicator for
      diagnostic and prognostic evaluation in EOC patients.

PMID- 29060929
TI  - MicroRNA-937 inhibits cell proliferation and metastasis in gastric cancer cells
      by downregulating FOXL2.
AB  - BACKGROUND: Despite advancement in the treatment, the mortality of gastric cancer
      remains high. MicroRNAs (miRNAs) are involved in tumor development and
      progression by regulating signaling pathways. In this study, we investigated the
      role of miR-937 in gastric cancer cells. METHODS: MiR-937 expression was
      determined in gastric cancer and matched normal tissues, and human gastric cancer
      cell lines by quantitative real-time PCR (qRT-PCR). Effects of miR-937 on cell
      proliferation, migration and invasion were analyzed by MTT and Transwell assays,
      respectively. In addition, the regulation of FOXL2 by miR-937 was evaluated by
      western blotting and luciferase reporter assays. Effects of FOXL2 on cell
      proliferation, migration and invasion were detected again. RESULTS: MiR-937 level
      was low expressed in gastric cancer tissues and cell lines. Overexpression of miR
      937 inhibited cell viability, colony formation and promoted apoptosis in gastric
      cancer cells. MiR-937 overexpression also inhibited cell migration and invasion
      by inhibiting the EMT process. Furthermore, we found that FOXL2 was a direct
      target of miR-937 and negatively regulated by miR-937. Moreover, miR-937
      overexpression inhibited the activation of the PI3K/AKT pathway. Furthermore, we
      found that overexpression of FOXL2 promoted cell viability, colony formation,
      migration, invasion, and inhibited apoptosis in gastric cancer cells.
      CONCLUSIONS: MiR-937 inhibits the proliferation and metastasis of gastric cancer
      cells by targeting FOXL2 via inactivation of PI3K/AKT signaling pathway. These
      results suggest that miR-937 may be a potential target for the treatment of
      gastric cancer.

PMID- 29060930
TI  - Downregulation of tissue miR-338-3p predicts unfavorable prognosis of gastric
      cancer.
AB  - Numerous studies have proved that microRNAs (miRNAs) play crucial roles in the
      tumorigenesis and progression of gastric cancer (GC). Our study was to
      investigate the correlation between miR-338-3p expression and clinical features
      as well as prognosis of GC. A total of 138 GC tissue specimens and adjacent non
      cancerous tissues were collected for further analysis, then quantitative PCR
      method was used to detect the relative miR-338-3p expression. Our study showed
      that tissue miR-338-3p level was greatly decreased in cancer tissues compared
      with paired normal tissues. Furthermore, loss of tissue miR-338-3p was positively
      associated with aggressive clinical characteristics (advanced clinical stage,
      poorer differentiation and lymph node invasion), shorter overall survival and
      recurrence free survival. Finally, tissue miR-338-3p expression was confirmed to
      be an independent prognostic factor for GC. Overall, our findings indicate that
      miR-338-3p acts as a tumor suppressor in GC and tissue miR-338-3p might serve as
      a novel prognostic biomarker of GC.

PMID- 29060931
TI  - Primary cardiac sarcoma complicated with cerebral infarction and brain
      metastasis: A case report and literature review.
AB  - In large autopsy series, the estimated frequency of primary tumors of the heart
      ranges from 0.0017% to 0.33%. Approximately 25% of primary cardiac tumors are
      malignant, and nearly 20% of these are sarcomas. To date, a completely feasible
      surgical resection remains the major treatment measure of cardiac sarcoma,
      especially for recurrent focal cardiac sarcoma and the recurrence of a
      restrictive metastasis. Although characteristically medical treatments are
      recommended, there is no consistent opinion for adjuvant radiotherapy and
      chemotherapy following an operation. Since these tumors usually undergo extensive
      spread by the time that the diagnosis is established, the prognosis of cardiac
      sarcoma remains poor. In this report, we described a case who underwent initial
      cardiac tumor resection, and was confirmed to be a pleomorphic undifferentiated
      sarcoma based on pathological findings. However, the patient complicated with
      cerebral infarction and subsequent brain metastasis sarcoma after the initial
      surgery, which was confirmed by brain tissue pathology. During the course of
      therapy, the patient underwent three surgical operations and refused to accept
      any chemotherapy and radiotherapy intervention. To the best of our knowledge,
      this is the first case report describing a primary cardiac sarcoma complicated
      with cerebral infarction and brain metastasis. The management of primary cardiac
      sarcoma is also discussed.

PMID- 29060932
TI  - miR-34a increases cisplatin sensitivity of osteosarcoma cells in vitro through up
      regulation of c-Myc and Bim signal.
AB  - BACKGROUND AND OBJECTIVE: Osteosarcoma is the most common primary malignancy in
      bone. Patients who respond poorly to induction chemotherapy are at higher risk of
      adverse prognosis. The molecular basis for such poor prognosis remains unclear.
      Recently, increasing evidence has suggested decreased expression of miR-34a is
      observed in a number of cancer types, including human osteosarcoma, and decreased
      miR-34a is involved in drug resistance. However, the underlying molecular
      mechanisms of decreased miR-34a on cisplatin chemoresistance in osteosarcoma has
      not been reported. METHODS: Osteosarcoma U2OS cells were transfected with miR-34a
      mimics for 48 h, then the cells were treated with 3.0 MUm cisplatin for 24 h.
      Using siRNA targeting c-Myc and Bim to examine the relation between miR-34a, c
      Myc and Bim expression exposure to cisplatin on cisplatin-induced apoptosis.
      RESULTS: Treatment of U2OS cells with cisplatin induced cell apoptosis by
      upregulation of c-Myc -dependent Bim expression; Osteosarcoma U2OS cells
      transfected with miR-34a mimics (miR-34a/U2OS) induced cell apoptosis and
      inhibited cell survival, and increased the sensitivity of U2OS cells to
      cisplatin. U2OS cells transfected with miR-34a mimics upregulated the protein
      expression of c-Myc and Bim. Targeting c-Myc downregulated the expression of Bim
      in the miR-34a/U2OS cells. In addition, Targeting Bim reversed the
      chemeresistance of miR-34a/U2OS cells to cisplatin. CONCLUSIONS: Our data
      indicated that miR-34a enhanced the sensitivity to cisplatin by upregulation of c
      Myc and Bim pathway.

PMID- 29060933
TI  - SUMO-specific protease 2-mediated deSUMOylation is required for NDRG2
      stabilization in gastric cancer cells.
AB  - N-myc downstream regulated gene 2 (NDRG2) is frequently down-regulated in various
      cancers and functions as a candidate tumor suppressor gene. NDRG2 has been shown
      to be SUMOylated on the lysine 333 residue, which promoted its ubiquitination and
      sequentially degradation by the SUMO-targeted ubiquitin E3 ligase RNF4. However,
      how to regulated NDRG2 deSUMOylation process remains largely unknown. Here, we
      report that Sentrin/SUMO specific protease (SENP2) was down-regulated in clinic
      gastric cancer samples and possessed a tumor-suppressive role in gastric cancer.
      At the molecular level, we found that SENP2 interacts with NDRG2 and mediates the
      de-SUMOylation process of NDRG2. Overexpression of SENP2 stabilized NDRG2,
      whereas silencing SENP2 caused rapid NDRG2 SUMOylation and degradation,
      indicating SENP2 antagonizes NDRG2 ubiquitination and degradation, thereby
      promoting the stability and function of this protein. Thus, our study reveals
      that SENP2 acts as a tumor suppressor which is deregulated in gastric cancer and
      the specific de-SUMOylation activity of SENP2 for NDRG2 is critical for it
      stabilization as well as gastric cancer cells proliferation.

PMID- 29060934
TI  - MiR-186 inhibits proliferation, migration, and invasion of non-small cell lung
      cancer cells by downregulating Yin Yang 1.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) is the main type of lung cancer.
      While miR-186 is significantly reduced in lung cancer tissues and cells, its role
      in NSCLC has not been completely elucidated. MATERIAL AND METHODS: We used qRT
      PCR and western blot methods to investigate the levels of miR-186 and YY1 in 21
      pairs of NSCLC tissues. Dual luciferase reporter gene assays were performed to
      detect whether miR-186 directly targets YY1. Next, the roles of miR-186 and its
      target gene (YY1) in determining the proliferation, apoptosis and migration
      capabilities of selected cell lines (A549 and HCC827) were investigated by using
      miR-186 mimics or YY1 siRNA. RESULTS: Our results showed that miR-186 was
      downregulated and YYI was upregulated in NSCLC tissue, and miR-186 expression was
      negatively associated with YY1. Similarly, miR-186 was also downregulated and YY1
      expression also was upregulated in both A549 and HCC827 cells; furthermore, miR
      186 was found to directly target YY1. Cell proliferation, invasion, and
      migration, as well as apoptosis induction were more strongly inhibited by YY1
      siRNA than by miR-186. CONCLUSION: Our results suggest that miR-186 and its
      target gene (YY1) could possibly serve as new prognostic biomarkers and
      therapeutic targets for treating NSCLC in humans.

PMID- 29060935
TI  - Frontiers of monoclonal antibodies: Applications in medical practices.
AB  - With the flourishing of innovation in drug discovery into a new era of
      personalized therapy, the use of monoclonal antibodies (mAbs) in the treatment of
      various ailments lies at the forefront. Major improvements in genetic sequencing
      and biomedical techniques as well as research into mAbs emphasize on determining
      new targets for advanced therapy while maximizing efficacy for clinical
      application. However, a balance has to be achieved concerning developing a target
      with low toxicity combined with high specificity and versatility, to allow a
      specific antibody to facilitate several biotic effects, ranging from
      neutralization of virus mechanisms to modulation of immune response and
      maintaining low global economic cost. Presently, there are approximately 30 mAbs'
      permitted for therapeutic use with many more being tested in clinical trials.
      Nevertheless, the heavy cost of mAbs' production, stowage and management as well
      as the subsequent hindrances to their development are outweighed by mAbs'
      clinical advantages. Compared to conventional drugs, since mAbs use as
      pharmacologic iotas have specific physical features and modes of action, they
      should be considered as a discrete therapeutic category. In this review, the
      history of mAb generation and the innovative technological applications of mAbs
      that has advanced in clinical practices is reviewed.

PMID- 29060936
TI  - Overexpression of Kinesin Superfamily Motor Proteins in Alzheimer's Disease.
AB  - Defects in motor protein-mediated neuronal transport mechanisms have been
      implicated in a number of neurodegenerative disorders but remain relatively
      little studied in Alzheimer's disease (AD). Our aim in the present study was to
      assess the expression of the anterograde kinesin superfamily motor proteins
      KIF5A, KIF1B, and KIF21B, and to examine their relationship to levels of
      hyperphosphorylated tau, amyloid-beta protein precursor (AbetaPP), and amyloid
      beta (Abeta) in human brain tissue. We used a combination of qPCR,
      immunoblotting, and ELISA to perform these analyses in midfrontal cortex from 49
      AD and 46 control brains. Expression of KIF5A, KIF1B, and KIF21B at gene and
      protein level was significantly increased in AD. KIF5A protein expression
      correlated inversely with the levels of AbetaPP and soluble Abeta in AD brains.
      Upregulation of KIFs may be an adaptive response to impaired axonal transport in
      AD.

PMID- 29060937
TI  - Situation Model for Situation-Aware Assistance of Dementia Patients in Outdoor
      Mobility.
AB  - BACKGROUND: Dementia impairs spatial orientation and route planning, thus often
      affecting the patient's ability to move outdoors and maintain social activities.
      Situation-aware deliberative assistive technology devices (ATD) can substitute
      impaired cognitive function in order to maintain one's level of social activity.
      To build such a system, one needs domain knowledge about the patient's situation
      and needs. We call this collection of knowledge situation model. OBJECTIVE: To
      construct a situation model for the outdoor mobility of people with dementia
      (PwD). The model serves two purposes: 1) as a knowledge base from which to build
      an ATD describing the mobility of PwD; and 2) as a codebook for the annotation of
      the recorded behavior. METHODS: We perform systematic knowledge elicitation to
      obtain the relevant knowledge. The OBO Edit tool is used for implementing and
      validating the situation model. The model is evaluated by using it as a codebook
      for annotating the behavior of PwD during a mobility study and interrater
      agreement is computed. In addition, clinical experts perform manual evaluation
      and curation of the model. RESULTS: The situation model consists of 101 concepts
      with 11 relation types between them. The results from the annotation showed
      substantial overlapping between two annotators (Cohen's kappa of 0.61).
      CONCLUSION: The situation model is a first attempt to systematically collect and
      organize information related to the outdoor mobility of PwD for the purposes of
      situation-aware assistance. The model is the base for building an ATD able to
      provide situation-aware assistance and to potentially improve the quality of life
      of PwD.

PMID- 29060938
TI  - Low Arousal Positive Emotional Stimuli Attenuate Aberrant Working Memory
      Processing in Persons with Mild Cognitive Impairment.
AB  - Emotional enhancement effects on memory have been reported to mitigate the
      pathophysiology of Alzheimer's disease (AD). However, relative to their
      manifestation in persons without pathologic aging, these effects may be reduced
      in magnitude or even deleterious, especially in tasks that more closely model
      ecologic memory performance. Based upon a synthesis of such reports, we
      hypothesized that in persons with AD low arousal positive stimuli would evoke
      relatively intact emotional enhancement effects, but that high arousal negative
      stimuli would evoke disordered emotional enhancement effects. To assess this,
      participants with and without mild cognitive impairment (MCI) presumed to be due
      to AD performed an emotionally-valenced short-term memory task while
      encephalography was recorded. Results indicated that for persons with MCI, high
      arousal negative stimuli led to working memory processing patterns previously
      associated with MCI presumed due to AD and dementia of the Alzheimer-type. In
      contrast, low arousal positive stimuli evoked a processing pattern similar to MCI
      participants' unaffected spouses. Our current findings suggest that low arousal
      positive stimuli attenuate working memory deficits of MCI due to AD.

PMID- 29060940
TI  - Everyday Memory in Patients with Alzheimer's Disease: Fragmentary and Distorted.
AB  - BACKGROUND: Errors of omission are an established hallmark of memory impairment
      in Alzheimer's disease (AD). Much less is known about other memory errors in AD
      such as false memories. OBJECTIVE: We investigated false memories in healthy
      elderly controls (HC; n = 23) and patients with AD (n = 20) using real-life tasks
      of watching news and commercials. METHODS: Participants received a comprehensive
      neuropsychological assessment and were shown original news and commercials with a
      subsequent recognition task to assess veridical and false memories. RESULTS:
      Subjective estimate of the number of errors were alike in HC and patients with
      AD. However, memory performance in both the news and the commercials task was
      significantly worse in patients with AD. Trail-Making Test and Symbol-Span Test
      were significant predictors of false memories on viewing news and commercials. In
      patients with AD, levels of Abeta1 - 42, but not levels of tau-protein were
      correlated with false memories in both tasks. CONCLUSIONS: Everyday life in
      patients with AD is impeded not due to the incompleteness of memory but also due
      to its distortions. Furthermore, it is hindered by the lack of awareness towards
      these deficits. False memory content in patients with AD is associated with
      Abeta42 levels in the CSF as a surrogate of the overall extent to which the brain
      has been affected by AD pathology. Future studies will need to address the impact
      of this duality of memory failure on everyday life of patients with AD and their
      proxies in greater detail.

PMID- 29060941
TI  - On one approach to health protection: Music of the brain.
AB  - This review presents the current status of a method for prevention and timely
      correction of human functional disturbances that was first proposed by Russian
      neurologist Ya.I. Levin in 1998 and further developed by the authors. The
      approach is named "Music of the Brain" and is based on musical or music-like
      stimulation organized in strict accordance with the biopotentials of a patient's
      brain. Initial studies on the music of the brain approach were analyzed, and its
      limitations were noted. To enhance the efficiency and usability of the approach,
      several combinations of music therapy with neurofeedback technique - musical
      neurofeedback - were developed. Enhanced efficiency of the approach has been
      shown for correction of functional disturbances during pregnancy and for
      elimination of stress-induced states in high technology specialists. The use and
      advantages of musical neurofeedback technology for increasing human cognitive
      activity, correcting sleep disturbances and treatment of disorders of attention
      were verified. After further development and testing the approach may be suited
      for a wide range of therapeutic and rehabilitation procedures in the protection
      of public health.

PMID- 29060939
TI  - Translational MRI Volumetry with NeuroQuant: Effects of Version and Normative
      Data on Relationships with Memory Performance in Healthy Older Adults and
      Patients with Mild Cognitive Impairment.
AB  - NeuroQuant (NQ) is a fully-automated program that overcomes several existing
      limitations in the clinical translation of MRI-derived volumetry. The current
      study characterized differences between the original (NQ1) and an updated NQ
      version (NQ2) by 1) replicating previously identified relationships between
      neuropsychological test performance and medial temporal lobe volumes, 2)
      evaluating the level of agreement between NQ versions, and 3) determining if the
      addition of NQ2 age-/sex-based z-scores hold greater clinical utility for
      prediction of memory impairment than standard percent of intracranial volume (%
      ICV) values. Sixty-seven healthy older adults and 65 mild cognitive impairment
      patients underwent structural MRI and completed cognitive testing, including the
      Immediate and Delayed Memory indices from the Repeatable Battery for the
      Assessment of Neuropsychological Status. Results generally replicated previous
      relationships between key medial temporal lobe regions and memory test
      performance, though comparison of NQ regions revealed statistically different
      values that were biased toward one version or the other depending on the region.
      NQ2 hippocampal z-scores explained additional variance in memory performance
      relative to % ICV values. Findings indicate that NQ1/2 medial temporal lobe
      volumes, especially age- and sex-based z-scores, hold clinical value, though
      caution is warranted when directly comparing volumes across NQ versions.

PMID- 29060942
TI  - Family and home in cognitive rehabilitation after brain injury: The importance of
      family oriented interventions.
AB  - Acquired brain injury (ABI) severely affects both the injured patient and her/his
      family. This fact alone calls for a therapeutic approach addressing not only the
      individual victim of ABI but also her/his family. Additionally, the optimal
      outcome of posttraumatic cognitive rehabilitation may be best obtained by
      supplementing the institution-based cognitive training with home-based training.
      Moving cognitive training and other therapeutic interventions into the home
      environment does, however, constitute an additional challenge to the family
      structure and psychological wellbeing of all family members. We presently argue
      in favour of an increased utilization of family-based intervention programs for
      the families of brain injured patients - in general and especially in case of
      utilization of home-based rehabilitative training.

PMID- 29060943
TI  - Towards a taxonomy of sexuality following traumatic brain injury: A pilot
      exploratory study using cluster analysis.
AB  - INTRODUCTION: Clinicians need to understand the heterogeneity of sexual problems
      following traumatic brain injury (TBI) for their adequate identification and
      treatment. OBJECTIVE: To systematically identify groups of individuals with TBI
      showing similar patterns of sexual functioning. METHODS: Forty-two individuals
      with TBI with a mean age of 37.9 years (SD = 9.7) and an average of 3.3 years
      post-injury (SD = 4.3). We included four primary measures in the cluster analysis
      (sexual quality of life questionnaire, sexual desire inventory, generalized
      anxiety disorder scale, and the patient health questionnaire for depression) and
      two secondary measures for cluster validation (post-concussion symptom scale and
      dysexecutive questionnaire). RESULTS: A hierarchical cluster analysis using the
      Ward method revealed the existence of two groups of individuals with TBI: a) with
      sexual problems who were older, showed lower levels of sexual quality of life and
      sexual desire, with significant symptoms of anxiety and depression, and b)
      without sexual problems who were younger, showed high levels of sexual quality of
      life and sexual desire, as well as low complaints of anxiety and depression.
      CONCLUSIONS: Clinicians must be more proactive in assessing sexual concerns,
      mostly when emotional and cognitive difficulties are present in older individuals
      with TBI, regardless of gender, chronicity and injury severity.

PMID- 29060944
TI  - A person-centered approach to study intimacy and sexuality in residential care
      facility (RCF) clients with dementia: Methodological considerations and a guide
      to study design.
AB  - BACKGROUND: The person-centered perspective of residential care facility (RCF)
      residents with dementia with regard to their intimate and sexual lives is largely
      neglected in research. OBJECTIVE: We aim to provide methodological considerations
      and reflections on a performed qualitative study. Recommendations and a guide to
      study design are provided to inform and encourage future research on the
      inclusion of people with dementia as participants. METHODS: Methodological
      recommendations and reflections are described in chronological order of the
      procedure. Fragments of interviews are included for further illustration and
      clarification. RESULTS: Considering preparation, close involvement of clinical
      practice, and extensive deliberation regarding study design tended to be
      important. Considering procedure, investment in contacts with clinical practice
      and authorized representatives; an introduction meeting; person-centered
      inclusion and consent; profound skills in interviewing participants with
      dementia; and flexibility in data collection were proven of importance.
      Considering data analysis and study quality, including field notes and aiming at
      a balance between study quality and practicability to enhance study 'rigor' were
      found important. CONCLUSION: Including the person-centered perspective in
      research on intimacy and sexuality of RCF residents with dementia, is challenging
      and takes a flexible and creative approach. It is, however, worthwhile to close
      the gap in literature.

PMID- 29060945
TI  - Art care: A multi-modality coronary 3D reconstruction and hemodynamic status
      assessment software.
AB  - BACKGROUND: Due to the incremental increase of clinical interest in the
      development of software that allows the 3-dimensional (3D) reconstruction and the
      functional assessment of the coronary vasculature, several software packages have
      been developed and are available today. OBJECTIVE: Taking this into
      consideration, we have developed an innovative suite of software modules that
      perform 3D reconstruction of coronary arterial segments using different coronary
      imaging modalities such as IntraVascular UltraSound (IVUS) and invasive coronary
      angiography images (ICA), Optical Coherence Tomography (OCT) and ICA images, or
      plain ICA images and can safely and accurately assess the hemodynamic status of
      the artery of interest. METHODS: The user can perform automated or manual
      segmentation of the IVUS or OCT images, visualize in 3D the reconstructed vessel
      and export it to formats, which are compatible with other Computer Aided Design
      (CAD) software systems. We employ finite elements to provide the capability to
      assess the hemodynamic functionality of the reconstructed vessels by calculating
      the virtual functional assessment index (vFAI), an index that corresponds and has
      been shown to correlate well to the actual fractional flow reserve (FFR) value.
      RESULTS: All the modules of the proposed system have been thoroughly validated.
      In brief, the 3D-QCA module, compared to a successful commercial software of the
      same genre, presented very good correlation using several validation metrics,
      with a Pearson's correlation coefficient (R) for the calculated volumes, vFAI,
      length and minimum lumen diameter of 0.99, 0.99, 0.99 and 0.88, respectively.
      Moreover, the automatic lumen detection modules for IVUS and OCT presented very
      high accuracy compared to the annotations by medical experts with the Pearson's
      correlation coefficient reaching the values of 0.94 and 0.99, respectively.
      CONCLUSIONS: In this study, we have presented a user-friendly software for the 3D
      reconstruction of coronary arterial segments and the accurate hemodynamic
      assessment of the severity of existing stenosis.

PMID- 29060948
TI  - Biosignal integrated circuit with simultaneous acquisition of ECG and PPG for
      wearable healthcare applications.
AB  - BACKGROUND: Wearable healthcare systems require measurements from
      electrocardiograms (ECGs) and photoplethysmograms (PPGs), and the blood pressure
      of the user. The pulse transit time (PTT) can be calculated by measuring the ECG
      and PPG simultaneously. Continuous-time blood pressure without using an air cuff
      can be estimated by using the PTT. OBJECTIVE: This paper presents a biosignal
      acquisition integrated circuit (IC) that can simultaneously measure the ECG and
      PPG for wearable healthcare applications. METHODS: Included in this biosignal
      acquisition circuit are a voltage mode instrumentation amplifier (IA) for ECG
      acquisition and a current mode transimpedance amplifier for PPG acquisition. The
      analog outputs from the ECG and PPG channels are muxed and converted to digital
      signals using 12-bit successive approximation register (SAR) analog-to-digital
      converter (ADC). RESULTS: The proposed IC is fabricated by using a standard 0.18
      MUm CMOS process with an active area of 14.44 mm2. The total current consumption
      for the multichannel IC is 327 MUA with a 3.3 V supply. The measured input
      referred noise of ECG readout channel is 1.3 MUVRMS with a bandwidth of 0.5 Hz to
      100 Hz. And the measured input referred current noise of the PPG readout channel
      is 0.122 nA/?Hz with a bandwidth of 0.5 Hz to 100 Hz. CONCLUSIONS: The proposed
      IC, which is implemented using various circuit techniques, can measure ECG and
      PPG signals simultaneously to calculate the PTT for wearable healthcare
      applications.

PMID- 29060946
TI  - Target of physiological gait: Realization of speed adaptive control for a
      prosthetic knee during swing flexion.
AB  - BACKGROUND: Prosthetic knee is the most important component of lower limb
      prosthesis. Speed adaptive for prosthetic knee during swing flexion is the key
      method to realize physiological gait. OBJECTIVE: This study aims to discuss the
      target of physiological gait, propose a speed adaptive control method during
      swing flexion and research the damping adjustment law of intelligent hydraulic
      prosthetic knee. METHODS: According to the physiological gait trials of healthy
      people, the control target during swing flexion is defined. A new prosthetic knee
      with fuzzy logical control during swing flexion is designed to realize the
      damping adjustment automatically. The function simulation and evaluation system
      of intelligent knee prosthesis is provided. Speed adaptive control test of the
      intelligent prosthetic knee in different velocities are researched. RESULTS: The
      maximum swing flexion of the knee angle is set between sixty degree and seventy
      degree as the target of physiological gait. Preliminary experimental results
      demonstrate that the prosthetic knee with fuzzy logical control is able to
      realize physiological gait under different speeds. The faster the walking, the
      bigger the valve closure percentage of the hydraulic prosthetic knee.
      CONCLUSIONS: The proposed fuzzy logical control strategy and intelligent
      hydraulic prosthetic knee are effective for the amputee to achieve physiological
      gait.

PMID- 29060949
TI  - A passive RFID-based location system for personnel and asset monitoring.
AB  - BACKGROUND: Typical radio frequency identification (RFID) access control system
      can be ineffective if an unauthorized person tailgates an authorized person
      through an access area. OBJECTIVE: To propose a system by using indoor locating
      and tracking techniques address this problem, which is to prevent unauthorized
      Alzheimer's and dementia patients from getting lost including by tailgating.
      METHODS: To achieve accurate target location, passive RFID deployment strategy is
      studied and a fingerprinting based passive RFID localization algorithm is
      proposed. The proposed system was evaluated in a building environment to simulate
      the performance of access control. RFID reader was installed on ceiling near the
      access area and tags were stitched on both shoulders of the experiment subject's
      garments. RESULTS: The probability of the error distance within 0.3 m achieved
      97% in the warning area; the location precision achieved 97% within 0.4 m in the
      monitoring area. CONCLUSIONS: The result showed that if an unauthorized person
      enters the restricted area, the system can initiate an alert signal accurately.
      Therefore, the proposed system is very suitable to be used in nursing home or
      hospital to prevent unauthorized personnel and assets entering/exiting a confined
      location.

PMID- 29060950
TI  - Fuzzy logic-based mobile computing system for hand rehabilitation after
      neurological injury.
AB  - BACKGROUND: Effective neurological rehabilitation requires long term assessment
      and treatment. The rapid progress of virtual reality-based assistive technologies
      and tele-rehabilitation has increased the potential for self-rehabilitation of
      various neurological injuries under clinical supervision. OBJECTIVE: The
      objective of this study was to develop a fuzzy inference mechanism for a smart
      mobile computing system designed to support in-home rehabilitation of patients
      with neurological injury in the hand by providing an objective means of self
      assessment. METHODS: A commercially available tablet computer equipped with a
      Bluetooth motion sensor was integrated in a splint to obtain a smart assistive
      device for collecting hand motion data, including writing performance and the
      corresponding grasp force. A virtual reality game was also embedded in the smart
      splint to support hand rehabilitation. Quantitative data obtained during the
      rehabilitation process were modeled by fuzzy logic. Finally, the improvement in
      hand function was quantified with a fuzzy rule database of expert opinion and
      experience. RESULTS: Experiments in chronic stroke patients showed that the
      proposed system is applicable for supporting in-home hand rehabilitation.
      CONCLUSIONS: The proposed virtual reality system can be customized for specific
      therapeutic purposes. Commercial development of the system could immediately
      provide stroke patients with an effective in-home rehabilitation therapy for
      improving hand problems.

PMID- 29060951
TI  - Systematic node management mechanism using ZigBee-based real-time vital sign
      information monitoring system to manage large numbers of patients.
AB  - BACKGROUND: Local hospitals must deal with large numbers of patients during mass
      casualty incidents, and the wireless sensor networks (WSNs) can help in these
      situations by monitoring vital signs. Conventional ZigBee nodes can obtain the ID
      of a device by assigning a unique 16-bit short address or by burning firmware
      into an IC. These methods tend to complicate node management and lack
      portability. OBJECTIVE: The study developed a node management mechanism to deal
      with a large number of patients in real-time, through the wireless monitoring of
      physiological signals. The mechanism proposed for the ZigBee WSN is based on a
      three-layer (Coordinator, Control Router, and End Device) tree topology. METHODS:
      The proposed system includes a node deployment process to formulate a ZigBee WSN
      as a tree topology, an algorithm to automatically number ZigBee nodes for
      monitoring and control system (MCS), and an algorithm to automatically obtain the
      short addresses of nodes for data collection. Specifically, an algorithm
      automatically collects data from ZigBee nodes for display on a computer graphical
      user interface (GUI). We also developed a reliable data transmission method
      capable of resolving the problem of packet loss. RESULTS: The proposed method has
      been applied in a local hospital. Our research findings provide a valuable
      reference for the development of ZigBee-based MCS. CONCLUSIONS: The proposed node
      management mechanism is faster, more reliable, and more intuitive to use, than
      traditional methods.

PMID- 29060952
TI  - An intelligent IoT emergency vehicle warning system using RFID and Wi-Fi
      technologies for emergency medical services.
AB  - BACKGROUND: Collisions between emergency vehicles for emergency medical services
      (EMS) and public road users have been a serious problem, impacting on the safety
      of road users, emergency medical technicians (EMTs), and the patients on board.
      OBJECTIVE: The aim of this study is to develop a novel intelligent emergency
      vehicle warning system for EMS applications. METHODS: The intelligent emergency
      vehicle warning system is developed by Internet of Things (IoT), radio-frequency
      identification (RFID), and Wi-Fi technologies. RESULTS: The system consists of
      three major parts: a system trigger tag, an RFID system in an emergency vehicle,
      and an RFID system at an intersection. The RFID system either in an emergency
      vehicle or at an intersection contains a controller, an ultrahigh-frequency (UHF)
      RFID reader module, a Wi-Fi module, and a 2.4-GHz antenna. In addition, a UHF ID
      antenna is especially designed for the RFID system in an emergency vehicle. The
      IoT system provides real-time visual warning at an intersection and siren warning
      from an emergency vehicle in order to effectively inform road users about an
      emergency vehicle approaching. CONCLUSION: The developed intelligent IoT
      emergency vehicle warning system demonstrates the capabilities of real-time
      visual and siren warnings for EMS safety.

PMID- 29060953
TI  - [Effect of Immunomodulators and Biologic Agents on Malignancy in Patients with
      Inflammatory Bowel Disease].
AB  - Immunosuppressive agents and biological agents are widely used for therapy in
      patients with inflammatory bowel disease (IBD). However, these therapies may be
      associated with an increased risk of malignancy. There is evidence that exposure
      of the therapeutic agents such as thiopurine and anti-tumor necrosis factor for
      IBD is associated with an increased risk of lymphoproliferative disorders, skin
      cancers, or uterine cervical cancers. This article reviews the malignancies
      associated with the use of immunosuppressive agents and biological agents in IBD.

PMID- 29060954
TI  - [The Additional Role of Symptom-Reflux Association Analysis of Diagnosis of
      Gastroesophageal Reflux Disease Using Bravo Capsule pH Test].
AB  - Background/Aims: Since the development of ambulatory esophageal pH monitoring
      test to diagnose gastroesophageal reflux disease (GERD), several parameters have
      been introduced. The aim of this study was to assess whether using the symptom
      index (SI), symptom sensitivity index (SSI), and symptom association probability
      (SAP), in addition to the DeMeester score (DS), would be useful for interpreting
      the Bravo pH monitoring test. Methods: A retrospective study, which included 68
      patients with reflux symptoms refractory to proton pump inhibitor (PPI) therapy
      who underwent a Bravo capsule pH test between October 2006 and May 2015, was
      carried out. Acid reflux parameters and symptom reflux association parameters
      were analyzed. Results: The median percent time of total pH<4 and DS were 2.90%
      (interquartile range [IQR] 1.13-6.03%) and 11.10 (IQR 4.90-22.80), respectively.
      According to the analysis of the day-to-day variation in percent time of total
      pH<4 (r=0.724) and DS (r=0.537), there was a significant correlation between Day
      1 and Day 2. The positive rate of Bravo test according to DS was 27 (39.7%).
      Although thirty patients experienced symptoms during the test, there were no
      significant differences of reflux parameters compared with other patients. In the
      symptom group, 7 patients (23.3%) were identified as having negative DS and an
      abnormal symptom-related index. There were no significant test-related
      complications. Conclusions: In addition to the analysis of traditional acid
      parameters of the Bravo capsule pH test, diagnosis of GERD, including reflux
      hypersensitivity, can be improved by performing an analysis of the symptom-reflux
      association and of the day-to-day variation.

PMID- 29060955
TI  - High and Frequent Dose of Dexlansoprazole and Amoxicillin Dual Therapy for
      Helicobacter pylori Infections: A Single Arm Prospective Study.
AB  - Background/Aims: Recently, the eradication rate of Helicobacter pylori (H.
      pylori) infection has decreased to less than 80% worldwide with the use of
      clarithromycin-based triple therapy owing to the increased resistance of H.
      pylori to antibiotics, especially clarithromycin and metronidazole. This
      prospective study aimed to determine eradication rate of H. pylori following high
      and frequent doses of extended-release dexlansoprazole and amoxicillin, as a dual
      therapy in a region with high clarithromycin resistance rate. Methods: A total of
      50 treatment-naive patients with active H. pylori infections, who were confirmed
      through via rapid urease test or histology and serology between November 2015 and
      February 2016 at our hospital, were included for analysis. All enrolled patients
      were treated with 750 mg amoxicillin and 30 mg dexlansoprazole, four times a day
      for a total duration of 14 days. Treatment success was determined using urea
      breath test four weeks after treatment completion. Results: Seven out of the 50
      patients (29 men and 21 women; mean age, 57 years) dropped out during the study.
      The total eradication rate was 52% (26/50), and that for those with a compliance
      rate of over 90% was 68.4% (26/38). H. pylori infections were not successfully
      eradicated in patients with a compliance rate of less than 90%. Nine patients
      (18%) reported side effects, such as mild diarrhea and abdominal fullness. No
      significant factors, such as smoking and alcohol consumption, affected the
      infection the eradication rate. Conclusions: High and frequent doses of proton
      pump inhibitor-amoxicillin dual therapy were not effective in eradicating H.
      pylori infection in a province with high clarithromycin resistance rate.

PMID- 29060956
TI  - [Serological Changes after Equivocal Helicobacter pylori-serology Test Findings
      Dependent on Gastric Secreting Ability].
AB  - Background/Aims: The serum anti-Helicobacter pylori (H. pylori) immunoglobulin G
      (IgG) and serum pepsinogen (PG) assays are widely used to screen for gastric
      cancer. An equivocal serology test finding indicates IgG titer between the
      positive and negative test findings. This study aims to evaluate the long-term
      follow-up result after an equivocal test finding on the serum anti-H. pylori IgG
      assay. Methods: Koreans aged 18 years or older with an equivocal serum anti-H.
      pylori IgG assay finding were included. Subjects were excluded if they did not
      undergo H. pylori serology test, serum PG assay, and upper gastrointestinal (UGI)
      endoscopy on the same day at our center. The annual test findings were followed
      up using the same methods. Results: Of the 7,178 subjects who underwent the serum
      assays and UGI endoscopy on the same day, 274 (3.8%) subjects showed an equivocal
      H. pylori serology test finding. Of the 98 subjects who were followed-up, 58
      (59.2%) showed seropositive finding at the mean follow-up period of 30.6+/-12.4
      months. Subjects with seroconversion showed a higher initial serum PG I (p=0.023)
      and PG II (p=0.036) levels than those without seroconversion. Conclusions: An
      equivocal H. pylori serology test finding was not rare (3.8%) in Korean adults,
      and 60% of equivocal subjects showed seroconversion within 3 years. Higher
      seroconversion rates in subjects with high PG I and PG II levels suggest that
      intact gastric secreting ability plays a role in the survival of H. pylori.
      Therefore, equivocal subjects with increased serum PG levels should be considered
      as potential seropositive subjects.

PMID- 29060957
TI  - The Etiologic Evaluation of Acute Pancreatitis in a General Hospital of Seoul
      Gyeonggi Province in Korea.
AB  - Background/Aims: In recent years, the incidence of acute pancreatitis (AP) has
      been increasing. A better understanding of the etiology is directly linked to
      more favorable outcomes. Unfortunately, there have been reports suggesting the
      variation of etiologies of AP across countries. The objective of this study was
      to determine the etiology of AP in a general hospital of Seoul-Gyeonggi province
      in Korea during the past decade. Methods: We retrospectively reviewed the medical
      records of consecutive patients with AP who were admitted to St. Paul's Hospital
      (Seoul, Korea) with an affiliation to the Catholic University of Korea between
      January 2003 and January 2013. Results: A total of 1,110 patients were enrolled,
      totaling 1,833 attacks, and the most frequent cause of AP was alcohol
      consumption. The recurrence rate of AP was 24.5% (272/1,110), and habitual
      recurrence rate (more than three times) was 12.6% (140/1,110). The rate of severe
      AP was 4.9% (90/1,833 attacks). The mortality rate of AP was 2.6% (29/1,110
      patients). The frequency of an idiopathic cause of AP was 13.3%. The recurrence
      rate and mortality rate of idiopathic AP were 16.2% and 5.4%, respectively. In
      41.7% (10/24) of cases of idiopathic AP, microlithiasis was suspected.
      Conclusions: Between 2003 and 2013 in Korea, alcohol was the most frequent cause
      of AP in the general hospital of Seoul-Gyeonggi province of Korea. It appears
      that alcohol abstinence program may be necessary. Further nationwide studies
      would be needed to evaluate the etiologies of AP.

PMID- 29060958
TI  - A Case of Hypertensive Crisis without a Surge in Adrenal Hormones after
      Radiofrequency Ablation as a Treatment for Primary Hepatocellular Carcinoma.
AB  - Radiofrequency ablation (RFA) is a minimally invasive procedure that has been
      considered as a relatively safe treatment for patients with small hepatocellular
      carcinoma (HCC). However, RFA has been shown to be associated with complications
      including mechanical and thermal damage. A 74-year-old man with hepatitis C virus
      associated HCC was admitted to our hospital. Abdominal computed tomography
      revealed two lobulated-HCC in segments 4 and 5. He had no medical history of
      hypertension and cardiac disease. During RFA, blood pressure was elevated to
      200/140 mmHg. There was no evidence of pulmonary embolism, aortic dissection, or
      ischemic heart disease. Laboratory findings for catecholamine surge were all
      within normal limits. After continuous intravenous nitroglycerin and oral beta
      blocker treatment, patient's blood pressure gradually decreased and back within
      the normal range. Hypertensive crisis after RFA treatment for HCC is rare. Most
      reported cases of hypertensive crisis during RFA were related to adrenal gland
      injury with a release of catecholamine. In our case, the site of HCC was not
      close to the adrenal gland, and there was no evidence of catecholamine surge.
      Herein, we report a very rare case of hypertensive crisis without a surge in
      adrenal hormones after RFA treatment for HCC.

PMID- 29060959
TI  - Intrahepatic Pancreatic Pseudocyst Complicated by Pancreatitis: A Case Report.
AB  - Pancreatic pseudocyst is a common complication of acute pancreatitis. Pseudocysts
      are commonly observed in the lesser sac and retroperitoneum; they are rarely seen
      in the liver. Herein, we report a case of intrahepatic pseudocyst, complicated by
      asymptomatic groove pancreatitis, that has successfully been treated with hepatic
      resection. A 70-year-old woman was referred to our hospital with severe upper
      abdominal pain. Abdominal computed tomography scan showed 11x10 cm sized cystic
      lesion in the left lateral section of the liver. Appearance of the pancreas was
      relatively normal. Endoscopic aspiration revealed a high level of amylase in the
      cystic fluid. After endoscopy, signs of peritonitis were observed; then, a left
      hemihepatectomy was performed. Pathologic examination revealed an intrahepatic
      pancreatic pseudocyst. The presence of intrahepatic cystic lesion in patients
      with suspected pancreatitis should raise the suspicion of intrahepatic
      pseudocyst. Intrahepatic pancreatic pseudocysts may be the only clinical
      manifestation even without an episode of acute pancreatitis.

PMID- 29060961
TI  - [Complications of gynecologic surgery: focus on deep venous thrombosis and
      pulmonary embolism].

PMID- 29060960
TI  - [Chinese expert consensus of prevention of deep venous thrombosis and pulmonary
      embolism after gynecologic surgery].

PMID- 29060962
TI  - [Clinical analysis of 19 pregnancies complicated listeriosis].
AB  - Objective: To analyze the clinical characteristics and perinatal outcomes of
      listeriosis during pregnancy. Methods: From July 2010 to April 2017, 70 131 women
      delivered in West China Second University Hospital. Nineteen cases were confirmed
      as listeriosis. The clinical symptoms, laboratory results, pathogens, placenta
      pathology and perinatal outcomes were analyzed retrospectively. Results: The
      median age of the 19 cases was 29.7 (19.0-42.0) years old. The median time before
      diagnosis was 4.8(0.5-19.0) days. The main clinical symptoms at first visits were
      high fever (17/19), increased white blood cells (18/19), abdominal pain (12/19).
      Listeria was found in samples of mother's blood (11/19), vaginal secretions
      (15/19), placenta (1/19), neonatal blood (4/19), neonatal phlegm (5/19) and
      neonatal ear secretions (1/19), respectively. Inflammation of placenta was
      identified in all 19 cases. Among the 19 cases, 1 was grade I chorioamnionitis, 4
      was grade II, 5 was grade III and 9 was grade VI. Only 4 newborn survived after
      therapy, and others suffered perinatal death, including 8 cases of intrauterine
      death, 3 cases of miscarriage and 6 cases of treatment failure. Conclusions:
      Listeriosis has characteristics of acute onset, quick development and high
      morbidity during pregnancy. The empiric use of antibiotics might not cover
      listeria. The understanding of listeriosis should be improved.

PMID- 29060963
TI  - [Prenatal diagnosis of 17q12 microdeletion syndrome in fetal renal
      abnormalities].
AB  - Objectives: To analyze 3 cases of 17q12 microdeletion syndrome diagnosed
      prenatally, and to demonstrate clinical phenotype of the syndrome in prenatal
      setting. Methods: From January 2013 to July 2017, 1 370 women received invasive
      prenatal diagnosis and chromosome microarray analysis (CMA) in Peking Union
      Medical College Hospital. Among them, 3 fetuses were diagnosed as 17q12
      microdeletion syndrome. All 3 cases were low-risk pregnancies. Abnormal
      structures in fetal kidney were found in all 3 cases, including 1 case of
      multiple renal cysts, 2 cases of bilateral hyperechogenic kidneys. These women
      accepted invasive prenatal diagnosis followed by karyotyping, parental
      fluorescence in situ hybridization or CMA validation. Results: The second and
      third trimester ultrasound showed that all 3 fetuses had bilateral renal
      structural abnormalities, including hyperechogenic kidney, multiple cysts and
      renal pelvis dilatation. The karyotyping of the 3 fetuses were normal. CMA
      examination showed that each case had 1.4-1.6 Mb deletion in 17q12 region. Two
      cases were de novo deletion and 1 case was inherited from the mother who had mild
      symptoms. The 3 women decided to terminate pregnancies after genetic counseling.
      Conclusion: 17q12 microdeletion syndrome is a recurrent chromosome microdeletion
      syndrome, and the unique phenotype in prenatal setting is the abnormal structure
      of bilateral kidneys. A few cases of 17q12 microdeletion syndrome even inherited
      normally phenotypical parents, and prenatal genetic counseling of 17q12
      microdeletion syndrome is relatively difficult.

PMID- 29060964
TI  - [Clinical analysis on hysteroscopic surgery for the treatment of type II cesarean
      scar pregnancy in the first trimester].
AB  - Objective: To investigate the safety and efficacy of hysterosopic management of
      type II cesarean scar pregnancy (CSP) and the value of prophylactic uterine
      artery embolization (UAE). Methods: Totally 104 patients with type II CSP treated
      with hysteroscopic surgery at the Women's Hospital, School of Medicine, Zhejiang
      University, during Jan. 2009 to Jun. 2016 were analyzed retrospectively, 67
      patients combined with UAE (UAE group) and 37 patients without combined with UAE
      (non-UAE group). Laparoscopy or sonography guidance was conducted simultaneously.
      The following clinical parameters were compared, including: primary cure rate,
      uterine packing rate, uterine perforation rate, hemoglobin level change, the time
      for the mass absorption and the return of beta-hCG to normal, complications,
      hospital days and hospital stay cost. Results: Median gestational age, size of
      mass, thickness of the anterior myometrium and beta-hCG level in UAE group versus
      non-UAE group were 47 versus 47 days, 30 versus 30 mm,2 versus 2 mm, 36 524
      versus 32 226 U/L (all P>0.05). Out of 104, 100 patients were managed
      successfully with hysteroscopic surgery, and 4 patients transformed to
      laparoscopic or laparotomy surgery. Hysteroscopic surgery was effective in 63 out
      of 67 patients (94%) in UAE group and 34 out of 37 patients (92%) in non-UAE
      group (P>0.05). There was no significant differences regarding uterine
      perforation rate, uterine packing rate, hemoglobin change and recovery time
      between UAE group and non-UAE group (all P>0.05). The median hospital day was 7
      days in UAE group versus 5 days in non-UAE group (P<0.01). The median hospital
      stay cost was 13 654 yuan in UAE group versus 9 108 yuan in non-UAE group
      (P<0.01). Serious complication occurred in 4 patients (6%, 4/67) in UAE group and
      2 patients (5%, 2/67) in non-UAE group (P=0.906). Conclusions: Hysteroscopic
      surgery is effective and safe for patients with type II CSP in the first
      trimester with size <=30 mm in diameter and gestation age<7 weeks. The value of
      prophylactic UAE is uncertain.

PMID- 29060965
TI  - [Clinical retrospective control study of single-port laparoendoscopic and multi
      port laparoscopic ovarian cystectomy].
AB  - Objective: To investigate clinical outcomes of laparoendoscopic single-site
      ovarian cystectomy compared with traditional multi-port laparoscopic ovarian
      cystectomy. Methods: Data of 81 patients with ovarian cystectomy from January
      2016 to May 2017, the single-site group (n=40) and the multi-port group (n=41) in
      Peking Union Medical College Hospital were retrospectively collected. The
      outcomes of single-site and multi-port groups were analyzed and compared,
      including: postoperative fever, operation time, blood loss, hemoglobin change,
      surgical complications, postoperative pain score, postoperative analgesic
      requirements, body image scale and cosmetic score, length of hospital stay,
      postoperative total cost. Results: No complication was found in two groups. No
      difference was found in postoperative fever, blood loss, hemoglobin change,
      postoperative pain score, length of hospital stay, and total cost between the two
      groups (all P>0.05). Operation time was (50+/-20) minutes in single-site group,
      and (40+/-15) minutes in multi-port group; postoperative analgesic requirements
      was 28%(11/40) in single-site group, and 7%(4/41) in multi-port group; cosmetic
      score was 22.6+/-2.6 in single-site group, and 17.3+/-2.6 in multi-port group;
      body image scale was 5.7+/-1.2 in single-site group, and 6.2+/-1.2 in multi-port
      group; these four clinical parameters were statistical differences (all P<0.05).
      Conculsion: Laparoendoscopic single-site ovarian cystectomy is feasible and safe,
      although it could't relieve the postoperative pian, it do offer a higher cosmetic
      satisfaction.

PMID- 29060966
TI  - [Clinical study of intensity modulated radiotherapy and three-dimensional
      conformal radiotherapy with three-dimensional brachytherapy and concurrent
      chemotherapy for patients with advanced cervical cancer].
AB  - Objective: To compare the dose, clinical efficacy and acute adverse reactions of
      intensity modulated radiotherapy (IMRT) and three-dimensional conformal
      radiotherapy (3D-CRT) combined with three-dimensional brachytherapy (3D-BT) in
      the treatment of concurrent radiotherapy and chemotherapy for advanced stage
      cervical cancer patients. Methods: Data collection was performed from January
      2011 to November 2015 in Chinese PLA General Hospital and Inner Mongolia Cancer
      Hospital. All 89 patients with advanced stage (II b-III b) cervical cancer were
      treated by pelvic radiotherapy and concurrent chemotherapy, 46 cases of them
      received IMRT and 3D-BT (IMRT group) , 43 cases received 3D-CRT and 3D-BT (3D-CRT
      group) , along with cisplatin chemotherapy. The dose accumulation of external
      beam radiotherapy and 3D-BT was calculated by deformable image registration to
      analyze clinical efficacy, acute adverse reactions and prognosis of the two
      groups. Results: (1) Dose of radiotherapy: planning target volume (PTV) coverage
      of IMRT group and 3D-CRT group were respectively (95.4+/-4.7)% and (95.1+/-5.1)%,
      without significant differences (t=0.289, P=0.773). Compared with the patients
      treated with 3D-CRT, the volumn receiving at least 30 Gy (V(30)), V(50) of
      rectum, colon, bladder and small intestine and V(20) of bone marrow in the IMRT
      group were significantly decreased (P<0.05). Regarding the combined dose, the
      maximum dose (D(max)) and the minimum dose received by the most exposed 2 cm(3)
      volume of the analyzed organ (D(2CC)) of rectum, colon, bladder and small
      intestine of IMRT group were significantly lower than those of 3D-CRT group
      (P<0.05). (2) Short-term efficacy: the effective rate of IMRT and 3D-CRT group
      were respectively 93% (43/46) and 91% (39/43), with no significant differences
      (chi(2)=0.237, P=0.626). (3) Acute adverse reactions: compared with 3D-CRT, IMRT
      could significantly reduce grade 1-2 acute toxicity in gastrointestinal
      [63%(29/46) vs 84%(36/43)], genitourinary [17%(8/46) vs 37%(16/43)] and
      hematologic [57%(26/46) vs 79%(34/43)] system (all P<0.05). There were no
      significant differences of grade 3 acute adverse reactions of gastrointestinal,
      genitourinary and hematologic system between two groups (all P>0.05). No grade 4
      acute adverse reactions were observed. (4) Prognosis: the overall survival rate
      at 1, 2-year of IMRT and 3D-CRT group were respectively 95.6%, 89.1% and 93.1%,
      86.1%. The progression-free survival rateat 1, 2-year of IMRT and 3D-CRT group
      were 91.1%, 89.1% and 88.4%, 86.1%, respectively. There were no significant
      differences in overall survival rate and progression-free survival rate between
      two groups (P>0.05). Conclusions: Compared with 3D-CRT, IMRT combined with 3D-BT
      has dosimetry advantages based on dose accumulation algorithms by deformable
      image registration. IMRT could ensure clinical efficacy and significantly reduce
      the incidence rate of acute toxicities.

PMID- 29060968
TI  - [The use and pitfalls of large randomized controlled trials].
AB  - Modern epidemiology is the art and science of investigating quantitatively
      regularities or general laws regarding applied healthcare issues. The validity of
      epidemiological studies is primarily determined by the study design and the
      precision by the sample size. Large randomized controlled trial (RCT) is thus the
      most rigorous and most precise epidemiological study design. Due to ethical
      concerns, RCTs can however be used only to evaluate medical interventions.
      Rigorousness of study design and sample size required for a study are inversely
      related to the anticipated size of effect to be evaluated: the smaller the
      effect, the more rigorous the study design and larger the sample size are
      required. Thus, large RCTs are necessary and called upon when and only when the
      effectiveness to be proved is relatively small; large effectiveness can be
      verified with small or medium-sized RCTs or even observational studies. In the
      stages of scientific research, large RCTs are confirmatory rather than original
      investigations on new hypotheses, whereas the value of a study is ultimately
      determined by the importance and novelty of the research question rather than
      methodology and the P value. Overemphasis on large RCTs has been causing: 1)
      overemphasis on interventions of small or moderate effect; 2) overemphasis on
      confirmatory studies and on size of study and funding and weakening original
      creative work; 3) increasing the risk of research resources, medical activities,
      and patients' well-being being hijacked by pharmaceutical companies.

PMID- 29060967
TI  - [Significance and expression of PAX8, PAX2, p53 and RAS in ovary and fallopian
      tubes to origin of ovarian high grade serous carcinoma].
AB  - Objective: To explore the origin of ovarian high grade serous carcinoma (HGSC)
      through analysing the expression and significance of PAX8, PAX2, p53 and RAS in
      the ovary and fallopian tube of different types and grades of serous carcinoma.
      Methods: A total of 44 cases tissue samples of ovarian tumor including 34
      malignant ovarian tumor and 10 normal normal tissue (as control group) were
      collected from the admitted patients in Affiliated Tumor Hospital of Guangxi
      Medical University from January 2015 to January 2016. Fallopian tube tissues were
      segmented in accordance with the fimbria, ampulla, isthmus and the corresponding
      ovarian tissues were by the side. There were 34 cases of patients with ovarian
      cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1
      mucinous carcinoma,1 endometrioid adenocarcinoma) and 5 non-epithelial ovarian
      cancer (sex cord-interstitial tumor). Among 27 cases of patients with ovarian
      serous cancer, there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC).
      One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer
      by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these
      samples were made tissue microarray. (1) To analyze the expression and
      differences of PAX8, PAX2, p53 and RAS in the above tissues and tissue microarray
      from ovarian and tubal of HGSC and control women by immunohistochemistry methods.
      (2) To compare the expression levels of PAX8, PAX2, p53 and RAS in ovarian and
      fallopian tubes of ovarian cancer patients with different pathological types. (3)
      To analyze the correlations of tubal and ovarian tissue in PAX8, PAX2, p53 and
      RAS expression of HGSC. (4) To analyze the factors of the prognosis of ovarian
      serous cancer in tissue microarray by single factor analysis method. Results: (1)
      PAX8, PAX2, p53 and RAS expression was negative in normal ovarian epithelium of
      control group, but the expression of PAX8, PAX2, p53 and RAS were strongly
      positive brown in secrete cells of normal fallopian tube epithelium. (2) p53 and
      RAS expression of fallopian tube epithelium in the epithelial ovarian cancer
      group were significantly higher than those in the non-epithelial ovarian cancer
      groups (P<0.05), but the expression of PAX8 and PAX2 in fallopian tube and the
      expression of PAX8, PAX2, p53 and RAS in ovarian tissue was not statistically
      significant in the groups (P>0.05). PAX8, PAX2 and p53 expression of the ovarian
      in HGSC group were significantly higher than those in LGSC group (P<0.05), while
      the expression of RAS was lower in the ovarian of the high-grade group (P<0.05),
      while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not
      statistically significant in the groups (P>0.05). (3) There was a significantly
      positive correlation between fallopian tube and the corresponding ovary of HGSC
      in PAX8 and PAX2 expression (r=0.422, P=0.045; r=0.693, P=0.000), but not
      correlation in p53 and RAS expression (r=0.058, P=0.793; r= -0.190, P=0.384). (4)
      Univariate survival analysis showed that the progression free survival time in
      patients with ovarian serous cancer group was significantly correlated with the
      protein expression of PAX8, PAX2 and RAS (P<0.05), but there were not correlated
      with age, surgical staging, cell differentiation, lymph node metastasis and
      preoperative chemotherapy and p53 protein expression (P>0.05). The total survival
      time in patients with ovarian serous cancer group was significantly correlated
      with the protein expression of PAX8 (P<0.05), but there were not correlated with
      age,surgical staging, cell differentiation, lymph node metastasis and
      preoperative chemotherapy and the protein expression of PAX2, RAS and p53
      (P>0.05). Conclusions: PAX8, PAX2, p53, RAS are of great significance for the
      study of origin of HGSC. HGSC may be derived from fallopian tube, but further
      investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be
      expected to be used as predictors of survival prognosis in patients with ovarian
      serous cancer.

PMID- 29060969
TI  - [Comprehensive evaluation on disease burden of injury and improvement of the
      related evidence system on injury prevention].
AB  - With rapid social and economic development in this country, injury has become one
      of the three major health issues with public concern. To reduce the burden of
      diseases as disability and medical treatment that caused by injury also became
      important in public health. Programs related to comprehensive evaluation on
      disease burden caused by injury and evidence-based strategies on injury-related
      prevention became substantially important. Our article- "The Disease Burden
      caused by Injury" , we involved a series of papers based on the systematic
      databases which focusing on the current status and the change of types of
      injuries in the Chinese population. Hopefully, it could provide key clues for the
      development of injury prevention and control programs in the future.

PMID- 29060970
TI  - [Disease burden on drowning in the Chinese population, in 1990 and 2013].
AB  - Objective: To comprehensively analyze the disease burden of drowning in the
      Chinese population both at the national and provincial levels in 1990 and 2013,
      to provide reference for the development of strategies regarding drowning
      prevention. Methods: Both methods related to unified measurement framework and
      standardized estimation on Global Burden of Disease in 2013, were used. Data on
      deaths caused by injuries were from the following sources which include: Disease
      Surveillance Points, the National Maternal and Child Health Surveillance Network,
      the Death Registration Reporting System of Chinese Center for Disease Control and
      Prevention, Death Registration System and death information from Macau and Hong
      Kong areas of China. Injury-related incidence data was from the National Injury
      Surveillance System and literature review. Parameters as death/death rate, years
      of life lost due to premature mortality (YLL)/standardized YLL rate, years living
      with disability (YLD)/standardized YLD rate and disability-adjusted of life years
      (DALY)/standardized DALY were used to analyze the disease burden and changing
      trend on drowning at both the national and all the provincial levels. Results: In
      2013, the number of deaths due to drowning was63 619 in China, with the
      standardized mortality rate as 5.29 per 100 000, accounting for 8.0% of the total
      injury deaths. Drowning was the fourth leading cause of injury death in the whole
      population and the first leading cause of injury death among children aged <5 and
      5-14 years old in 2013, with YLL of drowning as 3.49 million person years, YLD as
      0.04 million person years, and DALY as 3.53 million person years. Compared with
      data from 1990, the rates on standardized mortality, standardized YLL,
      standardized YLD and standardized DALY of drowning all declined in 2013. The five
      provinces/districts/cities with the highest rates of drowning were Xinjiang
      (10.08 per 100 000), Jiangxi (8.44 per 100 000), Anhui (7.92 per 100 000),
      Guizhou (7.77 per 100 000) and Sichuan (7.68 per 100 000). Standardized mortality
      of drowning reduced in all provinces in 2013. Conclusions: Disease burden of
      drowning in the Chinese population, especially in children, declined
      significantly in 2013, comparing to 1990. However, drowning remains a serious
      proble, with children and males in particular, in China. Research regarding
      prevention on drowning is in great need in the western and central areas where
      drowning mortalities appeared high.

PMID- 29060971
TI  - [Disease burden caused by violence in the Chinese population, in 1990 and 2013].
AB  - Objective: To analyze the disease burden of violence in the Chinese population,
      in 1990 and 2013. Methods: Indicators including mortality rate, years of life
      lost due to premature mortality (YLL), years lived with disability (YLD), and
      disability-adjusted of life years (DALY) related to violence, were extracted from
      the Global Burden of Disease 2013 and used to describe the burden of disease
      caused by violence in the Chinese population. Data related to corresponding
      parameters on disease burden of violence in 1990 and 2013 were described.
      Results: In 2013, a total of 20 500 people died of violent events, with the death
      rate as 1.44 per 100 000, in China. DALY caused by violence was 1.08 million
      person years in 2013. DALY caused by sharp violence was 0.47 million person
      years, with 0.09 million person years lost due to firearm violence. Disease
      burden caused by violence appeared higher in males than in females. When
      comparing with data from the 1990s, reductions were seen by 67.35% on the
      standardized death rate of violence, by 68.07% on the DALY attributable to
      violence, and by 70.47% on the standardized DALY rate attributable to violence,
      respectively, in 2013. Disease burden of violence among young adults and elderly
      was among the highest. When comparing with data from the 1990, DALY in 2013
      decreased among all the age groups except for the 70-year-old showed an increase
      of 9.36%. The standardized DALY rate in 2013 showed a declining trend in all the
      age groups, mostly in the 0-4-year-old group. The standardized DALY rates caused
      by sharp violence or firearm decreased by75.11% and 83.20% in the 0-4-year-old
      group. Conclusion: In recent years, the disease burden caused by violence showed
      a decreasing trend but appeared higher in males however with the increase of DALY
      in the elder population.

PMID- 29060972
TI  - [Disease burden on road injury in the Chinese population, in 1990 and 2013].
AB  - Objective: To explore the disease burden of road injuries in China. Methods: The
      results of Global Burden of Disease 2013 including death rate, disability
      adjusted of life years (DALY), years of life lost due to premature mortality
      (YLL), years lived with disability (YLD), were used to describe the burden caused
      by road injuries in 2013 and the trends from 1990 to 2013, in China. Results: In
      2013, there were 313 676 deaths caused by traffic accidents in China. Death rate,
      rates on DALY, YLL and YLD were 22.52 per 100 000, 1 076.54 per 100 000, 971.21
      per 100 000 and 105.34 per 100 000, respectively. Rates on deaths, YLL and YLD
      appeared higher in males, pedestrians than in females and other types of road
      travelers. Burden of injuries caused by traffic accidents was seen higher in
      those aged 15 to 49-year-old. From 1990 to 2013, the overall death rate on road
      injuries increased by 0.54 per 100 000 in China, with an increase of 2.34 per 100
      000 and 0.81 per 100 000, respectively in males and pedestrians. The rates on
      DALY, YLL and YLD decreased by 164.21 per 100 000, 115.06 per 100 000 and 49.06
      per 100 000, respectively. Conclusions: During the past 20 years, achievements
      had been made on road injury prevention and control, with the decrease of disease
      burden caused by road accidents. Males, young adults and pedestrians should be
      called for more attention to prevent road injuries.

PMID- 29060973
TI  - [Disease burden caused by suicide in the Chinese population, in 1990 and 2013].
AB  - Objective: To provide basic suicide prevention strategy through analyzing the
      disease burden of suicide in the Chinese population, in 1990 and 2013. Methods:
      Indicators including mortality rate, years of life lost due to premature
      mortality (YLL), years lived with disability (YLD), and disability-adjusted of
      life years (DALY) on suicide, were from the results of Global Burden of Disease
      2013 and used to describe the burden of disease caused by suicide in Chinese
      population. Data described the disease burden of suicide in China by comparing
      the corresponding parameters in 1990 and 2013. Results: In 2013, the standard
      mortality on suicide was 9.08 per 100 000, and 73.39 per 100 000 in the 80 and
      above year-old, with the highest rates on DALY and YLL seen in the 75-79-year
      old. Each parameter related to suicide burden in males appeared higher than that
      in females. Compare to data in the 1990s, these parameters declined in 2013,
      especially seen in females. The rate of YLLs/YLDs on suicide was 90.03 in 2013,
      89.83 in males and 89.00 in females. Conclusion: The disease burden of suicide
      decreased sharply between 1990 and 2013 but was still a serious issue in the
      elderly that called for more attention.

PMID- 29060974
TI  - [Disease burden on falls among elderly aged 70 and over in the Chinese
      population, in 1990 and 2013].
AB  - Objective: To analyze the disease burden of falls in Chinese population aged 70
      and over, in 1990 and 2013 and to provide evidence for the development of
      prevention strategies on falls in the elderly. Methods: Indicators including
      mortality rate, years of life lost due to premature mortality (YLL), years lived
      with disability (YLD) and disability-adjusted of life years (DALY) on falls, were
      gathered from the results of Global Burden of Disease 2013 and used to describe
      the disease burden of falls in China by calculating the changing rates on
      corresponding parameters in 1990 and 2013. Results: In 2013, the number of
      deaths, YLLs, YLDs, DALYs caused by falls among Chinese population aged 70 and
      over were 48 800, 0.44 million person years, 0.30 millions person years, and 0.74
      million person years, respectively. The standardized mortality rate, rates on
      YLLs, YLDs and DALYs of falls were 561.71 per 100 000, 55.87 per 100 000, 373.98
      per 100 000 and 929.85 per 100 000, respectively. The burden of falls increased
      along with the increase of age. Compared with 1990, the number of deaths, YLLs,
      YLDs and DALYs caused by falls increased by 308.80%, 161.01%, 54.67% and 104.47%,
      respectively, in 2013, more seen in males than in females. The standardized
      mortality rate, YLLs and DALYs caused by falls increased by 63.67%, 38.54% and
      73.08%, respectively, during 1990 and 2013. However, the standardized YLDs rate
      fell by 17.90% during the same period. Conclusion: Falls caused heavy disease
      burden which increased in 1990 and 2013 among the Chinese population aged 70 and
      over.

PMID- 29060975
TI  - [Disease burden of injuries in children aged 0-14-year-old in 1990 and 2013, in
      China].
AB  - Objective: To analyze the disease burden of injuries in Chinese children aged
      between 0-14-year-old, in 1990 and 2013. Methods: Data derived from the Global
      Burden of Disease 2013 was used to analyze the disease burden of injuries among
      children aged between 0-14-year-old in each province of China, using relevant
      indicators including mortality and the rate on disability-adjusted life years
      (DALY). Results: In 2013, the number of deaths, rates on mortality and DALY
      caused by injuries in children aged between 0-14-year-old were 73 766, 29.46 per
      100 000 and 2 449.36 per 100 000, respectively. Each indicator of injury burden
      appeared higher in boys than that in girls. With the increase of age, burden
      caused by injuries in each age group showed a decreasing trend. Provinces and
      autonomous regions as Xinjiang, Tibet, Gansu, Qinghai and Ningxia ranked the top
      5 regions on both mortality rate and DALY rate among children aged between 0-14
      year-old. The top 3 injury-related mortality rates and rate on DALY were
      drowning, road traffic injury and exposure to mechanic forces, among children.
      Compared to the disease burden of injuries in the 1990s, all indicators showed
      decreasing trends in children aged between 0-14-year-old, with girls more than
      boys, and variations in different age groups. In all areas of China, improvements
      were seen on intervention programs related to the injury-caused burden among
      children aged between 0-14-year-old, except for Ningxia, Yunnan and Chongqing.
      Conclusions: During the last two decades, there had been significant improvements
      in reducing the injury-caused burden among the Chinese children aged between 0-14
      year-old. However, injury is still the most important risk on health of children
      under 4-year-old, with boys in particular. Drowning and road traffic injury were
      the two leading causes of death in children aged between 1 and 14-year-old.

PMID- 29060976
TI  - [Status of daily life activities and respective risk factors among centenarian
      population in Hainan province].
AB  - Objective: To investigate the Activity of Daily life (ADL) among individuals aged
      100 and above, in Hainan. Methods: From June 2014 to December 2016, a community
      based cross-sectional study was conducted among individuals aged 100 and over in
      Hainan province. Data regarding basic information, ADL, prevalence of major age
      related diseases was collected in this population. Loss of ADL among these
      centenarians was described and its determinants examined. Results: The prevalence
      of ADL loss in centenarian population was 72.5%, with the top four items of ADL
      loss as stair-climbing (79.0%), moving (59.1%), walking (44.3%) and using toilet
      (41.3%). Results showed that tea consumption, good both on vision and audition
      were possible protective factors for the functions of ADL. Low level of education
      and vitamin D deficiency seemed as risk factors for the slowing-down of ADL
      (P<0.05). Conclusions: The prevalence of ADL loss among centenarians appeared
      relatively high. Years of education, tea consumption, degrees of vision, audition
      and vitamin D deficiency were possible risk factors responsible for the ADL loss
      in this centenarian population.

PMID- 29060977
TI  - [Current status of folic acid supplementation in women at child-bearing age in
      suburban area of Beijing].
AB  - Objective: To access the current status of folic acid supplementation in women at
      childbearing age in suburban area of Beijing, 2016. Methods: In this cross
      sectional study, a total of 722 women aged 17-41 years from six hospitals in
      suburban areas of Beijing were selected through cluster sampling. A questionnaire
      survey was conducted. Results: The rates of folic acid intake and regular folic
      acid intake among women under survey were 63.9% (456/714) and 83.3% (380/456). In
      women who remembered the duration of folic acid supplementation, the overall rate
      of preconceptional folic acid supplementation was 35.5% (159/450), in whom 27.3%
      (123/450) began to take folic acid 0-3 months before pregnancy; 8.0% (36/450)
      began to take folic acid 3 months before pregnancy. Multivariate logistic
      regression analysis indicated that household registering type, preparation for
      pregnancy or pregnancy, parity, smoking and alcohol use were the influencing
      factors for folic acid supplementation. Conclusions: The rate of folic acid
      supplementation remained low in childbearing aged women in suburban area of
      Beijing. It is necessary to further strengthen the health education about the
      importance of folic acid supplementation to improve the intake rate and the
      regular intake rate of folic acid in pregnant women and to promote maternal
      infant health and reduce the related complications.

PMID- 29060978
TI  - [Present situation and influencing factors on classroom mobile phone dependence
      syndrome in college students].
AB  - Objective: To explore the current situation and influencing factors on Classroom
      Mobile Phone Dependence Syndrome (CMPDS) among college students, and to provide
      scientific basis for guiding college students to use mobile phones reasonably and
      healthily. Methods: Stratified cluster sampling method was used. Students from
      different majors and different grades in Lanzhou University were included as the
      research objects. Classes were recognized as a unit in receiving basic field
      investigation in this questionnaire related study. Informed consent principles
      were followed and process of survey was anonymously carried out. Results: The
      overall rate of CMPDS in college students was 8.7%, including 'mild rate' as 6.6%
      and 'seriously mild rate' as 2.1%. No significant differences were found on
      genders or grades. Factors as shopping in the classroom shopping (OR=3.720),
      being bored on courses (OR=1.740), WiFi coverage (OR=1.787), time of practice in
      the classrooms (OR=1.514), and the total time of daily mobile phone use
      (OR=1.513) etc, appeared as risk factors related to CMPDS among the college
      students. However. shooting courseware (OR=0.579) appeared as a protective
      factor. Conclusions: Rate of CMPDS was high in college students and we suggested
      to form a joint task force among the college authority, teachers and students to
      work on the related problems. Hopefully, the serious CMPDS condition will be
      minimized and both physical and mental health of the college students be
      improved.

PMID- 29060979
TI  - [Evaluation on an intervention program related to adult tobacco use in Zhejiang
      province from 2010 to 2013].
AB  - Objective: To study the effect of adult tobacco use after the implementation of
      an intervention program, in Zhejiang province from 2010 to 2013. Methods: A total
      of 2 000 residents aged 15-69 years from 15 counties were selected, using a
      stratified multi-stage cluster sampling method and a face to face interview on
      questionnaire, in 2010 and 2013. Intervention program was then implemented.
      Results: The current smoking prevalence rates were 25.77% and 25.64% respectively
      in the above-said two years. Comparing data gathered from the 15-69 year olds in
      Zhejiang province in 2010 and 2013, no statistically significant differences were
      found in male population, in the 45-64 age group, in the rural population, and in
      the junior middle school students, regarding the current smoking prevalence
      rates. 42.11% and 40.56% of the current daily smokers started daily smoking
      within 30 minutes after waking up in the morning, in 2010 and 2013, and the
      difference was not significant. Conclusion: Prevalence of smoking in males in
      Zhejiang remained high,suggesting that publicity and education intervention
      methods of tobacco control should be effectively improved.

PMID- 29060981
TI  - [A cross-sectional study on HIV/AIDS "90-90-90" treatment target in Shandong
      province, 2015].
AB  - Objective: To analyze the status and its factors associated with HIV/AIDS- "90-90
      90" -treatment-target in Shandong province, China. Methods: Data regarding
      testing, treatment on HIV/AIDS in Shandong province by December 31, 2015 was
      collected. Chi-square test and logistic regression model were used to analyze
      related factors associated with the "90-90-90" -treatment-target. Results: Of the
      11 700 estimated HIV/AIDS, 61.2% were diagnosed, of whom 74.4% had received
      Highly active antiretroviral therapy (HAART) . More than 80% of the HIV/AIDS on
      HAART reached the criteria on viral suppression. HIV/AIDS infected by homosexual
      contacts were less likely to seek for diagnosis (P<0.05). HIV/AIDS lived in
      Qingdao city (OR=1.30, 95%CI: 1.05-1.60), Yantai city (OR=1.53, 95%CI: 1.02-2.31)
      and Weihai city (OR=1.96, 95%CI: 1.07-3.58) were more likely to receive HAART.
      HIV/AIDS patients that infected through homosexual or (OR=0.12, 95%CI:0.06-0.24)
      or heterosexual contacts (OR=0.13, 95%CI: 0.07-0.26), through injecting drug use
      (OR=0.08,95%CI: 0.03-0.17) or being diagnosed at the custodial institutions
      (OR=0.29, 95%CI: 0.21-0.41) were less likely to receive HAART. HIV/AIDS patients
      who received HAART at medical institutions (OR=1.81, 95%CI: 1.05-3.47) were more
      likely to meet the level of Viral load (VL) suppression. However, those who were
      infected through homosexual (OR=0.43, 95%CI: 0.25-0.75) or heterosexual contacts
      (OR=0.49, 95%CI: 0.28-0.81) or diagnosed at the custodial institutions (OR=0.48,
      95%CI: 0.28-0.80) were less likely to meet the criteria set for VL suppression.
      Conclusions: There was a gap between the status of testing/treatment and the
      target on HIV/AID "90-90-90" -treatment,especially on the target set for testing,
      in Shandong Province. Both HIV testing and comprehensive care services need to be
      strengthened.

PMID- 29060980
TI  - [Co-infections of HIV, syphilis and HSV-2 among men who have sex with men at the
      voluntary HIV counseling and testing clinics in Shanghai].
AB  - Objective: To understand the prevalence rates of HIV-syphilis and HIV-herpes
      simplex virus 2 (HSV-2) co-infections and related factors among men having sex
      with men (MSM) who had visited the voluntary HIV counseling and testing (VCT)
      clinics in Shanghai, China. Methods: 756 eligible MSM who attended the VCT
      clinics of Shanghai Municipality and Putuo district during March to August, 2015
      were recruited to participate in a cross-sectional survey with questionnaire
      interview and blood testing for HIV, syphilis and HSV-2. Results: A total of 732
      participants completed a valid questionnaire survey. The prevalence rates were
      3.3% (24/732) for HIV/Syphilis co-infection, 1.9% (14/732) for HIV/HSV-2 co
      infection, and 0.7% (5/732) for HIV/Syphilis/HSV-2 co-infection, respectively.
      HIV prevalence appeared significantly higher among syphilis-infected participants
      (45.3%, 24/53) than those without Syphilis (7.2%, 61/679) (chi(2)=63.11,
      P<0.001), and was also significantly higher among HSV-2 infected participants
      (34.1%, 14/41) than those without the HSV-2 infection (10.3%, 71/691)
      (chi(2)=21.49, P<0.001). Results from the Multivariate regression analysis
      indicated that participants who were migrants (OR=3.50, 95%CI: 1.01-12.17),
      having had middle school or lower levels of education (OR=4.46, 95%CI: 1.54
      12.87) or ever used illicit drugs (OR=4.25, 95%CI: 1.67-10.82, P=0.002) were
      under possible risks on HIV and Syphilis co-infection. Those participants who had
      high middle school or lower levels of education (OR=6.87, 95%CI: 1.86-25.42;
      OR=9.82, 95%CI: 2.25-42.85) were under risk on HIV and HSV-2 co-infection.
      Conclusion: HIV/Syphilis and HIV/HSV-2 co-infection were seen among MSM who
      attended the VCT clinics in Shanghai that called for special attention,
      especially on migrants, those with low education or illicit drug users.

PMID- 29060982
TI  - [Epidemiological characteristics of newly reported HIV infections in Chinese and
      Burmese residents, during 2012-2016 in Dehong Dai and Jingpo Autonomous
      Prefecture, Yunnan province].
AB  - Objective: To understand the epidemiological characteristics of newly reported
      HIV infections in Chinese and Burmese residents during 2012-2016 in Dehong Dai
      and Jingpo Autonomous Prefecture of Yunnan province (Dehong) and to provide
      evidence for the development of related programs on prevention and control.
      Methods: All the HIV infections who were newly reported during 2012-2016 in
      Dehong, were recruited as the study subjects, with epidemiological
      characteristics of the cases analyzed by using the software SPSS 22.0. Results: A
      total of 5 692 HIV infections were newly reported between 2012 and 2016
      (including 5 592 in this study), in which the Chinese patients accounted for
      43.3% (2 419) and the rest 56.7% (3 173) were Burmese. Differences in age, gender
      and other social characteristics of these newly reported HIV infections were
      statistically significant between the Chinese and the Burmese (all p-values
      <0.05). Most cases were males and between the age of 20-49 years old. Other
      characteristics of the patients would include: having had primary school
      education, married, being farmers, and with CD(4)(+)T cells counts >=350
      cells/MUl. HIV infection was mainly transmitted through sexual contact among the
      Chinese patients but through injecting drug use among the Burmese patients.
      Conclusions: Epidemiological characteristics of the newly reported HIV infections
      were different between the Chinese and the Burmese, between 2012 and 2016 in
      Dehong. Targeted prevention and control programs should be taken.

PMID- 29060983
TI  - [A 22-year-follow-up cohort study on primary liver cancer in Haimen city of
      Jiangsu province].
AB  - Objective: A prospective cohort study was carried out to assess the mortality and
      potential risk factors for primary liver cancer (PLC) in Haimen city of Jiangsu
      province. Methods: The cohort involved 89 789 adult residents aged 25-69 years.
      Upon the entry of this project, each subject was asked to complete a
      questionnaire and to provide a blood sample of 10 ml. Surface antigen of
      hepatitis B virus (HBsAg) was tested by radioimmunoassay. All the subjects were
      followed-up every year for vital statistics and death certificate information
      until 2014. Cox proportional hazard model was used to estimate the hazard ratio
      (HR) and 95% confidence interval (95%CI) for PLC mortality associated with HBsAg
      status and other risk factors. Results: During the 1 299 611 person-years of
      follow-up, a total of 2 583 PLC cases were identified, including 2 149 men and
      434 women. Mortality of the PLC for men and women were 247.80/100 000 person
      years and 100.38/100 000 person-years, respectively. Among those who died of PLC,
      73.87% had been tested HBsAg positive. HBV infection seemed the predominant risk
      factor for PLC and the HRs were 15.97 for men (95%CI: 14.29-17.85) and 21.63 for
      women (95%CI: 16.16-28.96) respectively. Ageing, cigarette smoking, previous
      history of hepatitis, and family history of HCC were factors associated with the
      increased risk for PLC. Conclusion: People living in Haimen city had a high risk
      on PLC. HBV infection appeared the most important risk factor for HCC mortality
      in this area.

PMID- 29060984
TI  - [Epidemiologic and spatio-temporal characteristics of hepatitis E in China, 2004
      2014].
AB  - Objective: To describe and analyze the epidemiologic and spatio-temporal
      characteristics of hepatitis E in China from 2004 to 2014. Methods: Data on the
      incidence of hepatitis E in 31 provinces (municipality and autonomous region)
      from 2004 to 2014, were collected. Empirical Mode Decomposition (EMD) was applied
      to decompose the time-series data to accurately describe the trend of hepatitis E
      incidence. Mathematic model was used to estimate the annual change of incidence
      in each age group and the whole province. Software ArcGIS 10.1 and SaTScan 9.01
      were used to analyze the spatio-temporal clusters. Results: During 2004-2014, a
      total of 245 414 hepatitis E cases were reported in China. The overall incidence
      showed a slight increase (OR=1.05, 95%CI: 1.03-1.10). Incidence rates on
      hepatitis E were discovered different across the provinces, with significant
      increase appearing in the southern, central and northwestern areas. The highest
      increase was seen in the elderly, especially in the 65-69 and 70-74 year-olds.
      Results from the Local spatial autocorrelation analysis showed that the "high
      high cluster" was moving from the north to the south and the "low-low cluster"
      disappeared as time went by. Data from Spatio-temporal scanning showed that there
      were five spatio-temporal clustering areas across the country. Conclusion: The
      overall incidence of hepatitis E was on the rise from 2004 to 2014, in China, but
      with differences seen across the areas and age groups.

PMID- 29060985
TI  - [Characteristics of spatiotemporal distribution on severe fever with
      thrombocytopenia syndrome in Henan province].
AB  - Objective: To explore the characteristics regarding temporal, spatial and
      spatiotemporal distribution on severe fever with thrombocytopenia syndrome (SFTS)
      in Henan province. Methods: Surveillance data related to SFTS was collected in
      Henan province, from year 2014 to 2016. Descriptive method was used to analyze
      the distribution of SFTS. 1.7.0 software related to the Public health geographic
      information system (PHGIS), was applied to draw the spatial distribution map of
      SFTS. Chi-square test was used to compare the different incidence rates. Results:
      A total of 2 781 SFTS cases, including 34 deaths, were reported in Henan province
      from 2014 to 2016, with an average annual fatality rate as 1.22%. There were
      statistically significant differences for the incidence rates of SFTS between
      different years (P<0.01). Cases were mainly concentrated from April to October,
      which accounted for 96.66% of the total number, with the incidence peak seen in
      May. Incidence rates of SFTS in spring, summer, autumn were higher than that in
      winter. The cases were scattering around in 26 counties of 8 cities. Xinyang city
      reported 2 714 cases, accounting for 97.59% of the total number of cases in the
      province. The average annual incidence rate in Xinyang city was 17.22 per 100
      000, much higher than that for the whole Henan province (0.98 per 100 000), with
      statistically significant difference (P<0.01). Six counties reported having death
      cases, that accounted for 23.08% of the total number of counties, reported to
      have death cases. Two kinds of incidence patterns of SFTS were noticed in Henan
      province, with aggregation in some local regions or sporadic in individual
      counties. The number of counties with reporting cases increased annually. The
      epidemic area was expanding and gradually spreading from south to north areas of
      the province. Conclusions: SFTS was characterized with both temporal and spatial
      clusters in Henan province. Effective prevention and control measures should be
      made in accordance with the spatiotemporal distribution and the trend on SFTS.

PMID- 29060986
TI  - [Epidemiological characteristics on temporal-spatial distribution of varicella in
      Guangxi Zhuang Autonomous Region, 2014-2016].
AB  - Objective: To analyze the epidemiological characteristics of temporal-spatial
      distribution on varicella in Guangxi Zhuang Autonomous Region (Guangxi) during
      2014 to 2016. Methods: Incidence data on varicella was collected from the
      National Notifiable Infectious Disease Reporting Information System (NNIDRIS) of
      the Center for Disease Control and Prevention (CDC) while geographic information
      data was from the national CDC. ArcGIS 10.2 software was used to analyze global
      and local spatial auto correlation on spatial clusters. SaTScan v9.1.1 was used
      to conduct temporal-spatial scan for exploring the areas of temporal-spatial
      clusters. Results: The overall incidence rates of varicella during 2014 to 2016
      were 32.48/100 000, 43.56/100 000 and 61.56/100 000 respectively. Incidence of
      varicella showed a positive spatial auto correlation at the county level (the
      value of Moran's I was between 0.24 to 0.35, P<0.01), with consistent high
      morbidity. High-high cluster areas were seen and mainly concentrated in the north
      western areas of Guangxi. Result from the temporal-spatial scan showed that
      temporal cluster of varicella occurred mainly between October and next January
      while the type I cluster area was mainly distributed in all of the counties in
      Hechi city and most counties of Baise city, with most counties being covered in
      the north-western areas of Guangxi, during 2014-2016. When comparing to data from
      the last two years, two type II cluster areas with larger scales were formed in
      the north-eastern area of Guanyang county and Haicheng county of southern area in
      Guangxi, in 2016. Conclusions: Incidence on Varicella seemed on the rise, and the
      distribution of cases showed clustered features, both on time and space.
      Strategies regarding control and prevention on Varicella should focus on high
      high clustered areas, namely north-western areas of the province, including
      surrounding areas during the high onset season.

PMID- 29060987
TI  - [Epidemics and risk factors of plague in Junggar Basin, Xinjiang Uygur Autonomous
      Region, 2007-2016].
AB  - Objective: To explore the epidemic situation of animal plague in Junggar Basin
      natural plague foci. Methods: Data on epidemics of plague and on population
      involved, as well as results on antibodies and pathogens, were analyzed. Samples
      on animals and vectors were collected from 18 counties in Junggar Basin plague
      natural foci between 2007 and 2016. Results: The density of Rhombomys (R.) opimus
      was temporally fluctuant, from 2.1/hm(2) to 22.6/hm(2) respectively. However, the
      spatial distribution appeared asymmetrical, with the highest seen in Kelamayi and
      Wumuqi-midong counties, as 14.2/hm(2) and 13.0/hm(2) respectively. Rates of
      capture on nocturnal rodents were from 4.2% to 10.1%, with the highest rate as
      10.1% in 2014. Meriones meridianus appeared the dominant species in the nocturnal
      community of rodents, which accounted for 81.9%. Regarding the spatial and
      temporal distributions, rates of R. opimus with fleas appeared fluctuant, with an
      average rate as 90.7% and the average total flea index was 10.44. In flea
      community of R. opimus, Xenopsylla (X.) skrjabini was found the dominant species,
      popular in distribution and accounted for 47.8%. The average rate of nocturnal
      rodents with flea was 20.2%, with total flea index as 1.20 and the dominant fleas
      were X. conformis conformis and Nosopsyllus laeviceps. A total of 13 species with
      9 087 serum samples from rodents were detected as having Y. pestis antibody by
      IHA, with 617 positive samples. Of them, the positive rate of having R. opimus
      appeared the highest (9.4%), followed by D. sagitta (1.1%). Spatially, two
      clustered areas were found, with one in the eastern Junggar Basin from Changji to
      Mulei county, with the antibody positive rates of R. opimus as 14.3%. The other
      one was in the central area of Junggar Basin, including Kelamayi, Shawan and Wusu
      counties, with the antibody positive rate as 13.6%. The prevalence of plague on
      R. opimus was fluctuant, with the lowest seen in 2008, with the average antibody
      positive rate of R. opimus as 1.0% and the highest as 19.3% in 2013. A total of
      18 strains were isolated from 2007 to 2016. However, most of the strains were
      isolated from R. opimus and parasitic fleas, accounted for 8/9, in Kelamayi,
      Wulumuqi-midong and Jimusaer, respectively. Conclusions: Complex ecosystem was
      seen in the Junggar Basin natural plague foci, with the multiple composition of
      species and different community structure of hosts and vectors, plus the
      flustering prevalence. Animal plague was seen in the whole region with succession
      of the plague nature foci. Passive transmission of plague between human beings
      and animals through close contacts was seen which was driven by economic benefits
      to some degree.

PMID- 29060988
TI  - [Relationship between air pollution exposure during pregnancy and birth weight of
      term singleton live-birth newborns].
AB  - Objective: This study explored the association between air pollution exposure and
      birth weight by using the multilevel linear model, after controlling related
      meteorological factors and individual differences of both mothers and babies.
      Methods: Women of childbearing age who were pregnant in Xi'an from 2010 to 2013,
      were selected as objects of this study. Multistage random sampling method was
      used to select 4 631 subjects followed by a self-designed questionnaire survey.
      Data related to quality of air and meteorology were gathered from routine
      monitoring system. Gestational age and date of birth, together with the average
      levels of air pollution were calculated for each trimester on each mother, and
      then the impact of air pollution on birth weight was assessed. A multilevel
      linear model was employed to investigate the association between the levels of
      exposure to air pollution by birth weight. Confounding factors were under
      control. We established three models in this study: Model 1 which involving the
      variable of air pollution exposure. Model 2 was adjusted for variables in Model 1
      plus some other individual differences of both mother and baby. Model 3 was
      adjusted for variables in Model 2 plus meteorological factors. Results: There
      were significant differences seen in birth weight within the subgroups of gender,
      gestational age, mother's reproductive age, maternal education, residential areas
      and family incomes (P<0.01) of the infants. However, there was no difference
      found in Model 1 (P>0.05). Data from Model 3 indicated that a decrease of 13.3
      g(10.9 g in Model 2) and 6.6 g (5.9 g in Model 2) in birth weight that were
      associated with an increase of 10 MUg/m(3) in the average level of NO(2) and
      PM(10) during the second trimester; A decrease of 13.7 g (9.8 g in Model 2) in
      birth weight was associated with an increase of 10 MUg/m(3) in the average level
      of NO(2) during the third trimester. Conclusion: After controlling for
      meteorological factors, the levels of exposure to NO(2) and PM(10) during the
      second trimester and NO(2) during the third trimester were negatively associated
      with birth weight.

PMID- 29060989
TI  - [Association and effects of gene-gene interactions between peroxisome
      proliferator-activated receptor and pulse pressure].
AB  - Objective: To investigate the association between ten single nucleotide
      polymorphisms (SNPs) in the peroxisome proliferator-activated receptors and pulse
      pressure (PP) as well as the relationships between gene-gene interaction between
      PPARalpha/delta/gamma genes and PP. Methods: A total of 820 subjects, with 550
      females and 270 males, were recruited from a cohort study of "Prevention of
      Metabolic Syndrome and Multi-metabolic Disorders in Jiangsu Province of China
      Study (PMMJS)" . Ten SNPs of PPARalpha/delta/gamma genes were selected. GMDR
      software (version 1.0.1) was used to evaluate the gene-gene interactions among
      PPARs SNPs associated with PP. Results: The mean levels of PP in people with
      mutant genotype of rs1805192 in PPARgamma genes (PA+AA) showed a significant
      increase by 1.341 mmHg (95%CI: 0.431-2.252 mmHg) when compared to the persons
      with wild genotype (PP). In the subgroup of subjects with more than 30 mmHg
      levels of PP, a six-locus model comprised rs135539 of PPARalpha, rs2016520 of
      PPARdelta, rs10865710, rs1805192, rs709158 and rs3856806 of PPARgamma showed a
      highest level of prediction accuracy (0.577) and displayed a better cross
      validation consistency (10/10). In the subgroup of subjects with less than 40
      mmHg levels of PP, a two-locus model was statistically associated with PP with
      0.628 of prediction accuracy and 10/10 of cross-validation consistency.
      Conclusion: PPARgamma rs1805192 was associated with the occurrence of PP. Gene
      gene interactions among rs135539 of PPARalpha, rs2016520 of PPARdelta,
      rs10865710, rs1805192, rs709158 and rs3856806 of PPARgamma were all significantly
      related to PP.

PMID- 29060990
TI  - [Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in
      neonates and its influence on HBV intrauterine transmission].
AB  - Objective: To explore the relationship between HBeAg in HBsAg positive mothers
      and CD(4)(+)CD(25)(+)Foxp3(+)regulatory T cells (Treg) in newborns, as well as
      how they would influence the increasing risk on HBV intrauterine transmission.
      Methods: We collected information on general demographic characteristics and
      delivery on 270 HBsAg positive mothers and their newborns from the Third People's
      Hospital of Taiyuan. Fluorescence quantitative polymerase chain reaction (FQ-PCR)
      and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV
      serological markers in peripheral blood from both mothers and neonates. The
      expression of Treg and other immune cells in peripheral blood of neonates were
      detected with flow cytometry (FCM). Results: Maternal HBeAg positive rates were
      associated with an increased risk of intrauterine transmission (OR=4.08, 95%CI:
      1.89-8.82). Rates of Treg in newborns born to HBsAg-positive mothers were higher
      than that of the negative group (Z=2.29, P=0.022). Each pair of the subjects was
      assigned to five different groups according to the HBeAg titers of mothers.
      Frequencies of both Treg and HBeAg in newborns and HBV DNA in mothers between the
      above said 5 groups showed similar trends of changing patterns and the
      differences between groups were statistically significant(chi(2)=18.73, P<0.001;
      chi(2)=181.60, P<0.001; chi(2)=183.09, P<0.001). Results from partial correlation
      analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA,
      mother's HBeAg titers were positively related to the percentage of Treg in their
      newborns (r(s)=0.19, P=0.039). In addition, the frequencies of Treg were
      negatively correlated with pDC and CD(4)(+) T cell in their newborns (r(s)=-0.21,
      P=0.017; r(s)=-0.23, P=0.009). Conclusion: HBeAg from HBsAg positive mothers
      might have inhibited the function of neonatal DC cells and T cells to reduce the
      immune response to HBV by up-regulating the proportion of Treg and finally
      increased the risk of HBV intrauterine transmission.

PMID- 29060992
TI  - [A systematic review of international simulation models on the natural history of
      breast cancer: current understanding and challenges for Chinese-population
      specific model development].
AB  - Objective: To systematically review the worldwide simulation model studies on the
      natural history of breast cancer and to summarize related parameters. Methods: A
      structured literature search was conducted in PubMed and the Cochrane Library to
      identify articles during 1980-2015. Articles were screened independently by two
      researchers. Health states in the natural history and relevant parameters were
      extracted. Results: A total of 36 studies were included for analysis, within the
      earliest one was published in 1990. Most studies were from Europe and America
      countries, and 2 studies from China. Markov model was mostly applied to
      evaluating breast cancer screening programs (n=32). Reported health status
      included "healthy" (n=36), ductal carcinoma in situ (DCIS, n=17), invasive breast
      cancer (IBC, n=36), and death (n=27). There were two definite classifications for
      IBC, tumor size (n=9) and TNM staging (n=9, 3 studies reported transition rates).
      The median (range) of annual transition rates from DCIS to stage-I IBC, I to II,
      II to III, III to IV were 0.279 (0.259-0.299), 0.150 (0.069-0.430), 0.100 (0.060
      0.128) and 0.210 (0.010-0.625), respectively. A total of 15 studies reported the
      mean duration from predinical to clinical stage for IBC was 1.95-4.70 years,
      which gradually increased with age, and 7 studies reported that for DCIS.
      Conclusions: Despite closer attention was paid to breast cancer natural history
      models, in recent years atypical hyperplasia has been neglected. Data on the mean
      duration of DCIS requires reasonable conversion. Various classifications for IBC
      exist whereas transition rates are limited. Current findings would be valuable
      references but challenging for the Chinese-population specific natural history
      model, development.

PMID- 29060991
TI  - [Influence of intrahepatic cholestasis during pregnancy on the incidence of
      preterm birth].
AB  - Objective: Intrahepatic cholestasis during pregnancy (ICP) and its relation to
      incidence of preterm birth (PTB) were under study. Methods: A prospective cohort
      study was carried out that including all the hospitalized pregnant women with
      live singleton births, from January 2014 to March 2015 in Anqing Municipal
      Hospitals. Informed consent was followed in every pregnant woman with related
      demographic information collected through questionnaire and hospital electronic
      medical record system. Both univariate and multi-variate statistical methods were
      used to analyze the relations between ICP and incidence of PTB. Results: A total
      of 2 758 pregnant women were included in this study. The incidence proportions of
      ICP and PTB appeared as 7.25% and 16.28% respectively. Results from the logistic
      regression analysis showed that ICP increased the risk of both overall PTB
      (RR=2.33, 95%CI: 1.67-3.25) and medically indicated PTB (RR=8.46, 95%CI: 5.45
      13.12), but not the spontaneous PTB (RR=0.94, 95%CI: 0.57-1.54). Conclusion: ICP
      seemed to have increased the risk on medically indicated PTB but not the
      spontaneous PTB.

PMID- 29060993
TI  - [Development of HIV infection risk assessment tool for men who have sex with men
      based on Delphi method].
AB  - Objective: To develop a HIV infection risk assessment tool for men who have sex
      with men (MSM) based on Delphi method. Methods: After an exhaustive literature
      review, we used Delphi method to determine the specific items and relative risk
      scores of the assessment tool through two rounds of specialist consultation and
      overall consideration of the opinions and suggestions of 17 specialists. Results:
      The positivity coefficient through first and second round specialist consultation
      was 100.0% and 94.1%, respectively. The mean of authority coefficients (Cr) was
      0.86. Kendall's W coefficient of the specialist consultation was 0.55 for the
      first round consultation (chi(2)=84.426, P<0.001) and 0.46 for the second round
      consultation (chi(2)=65.734, P<0.001), respectively, suggesting that the
      specialists had similar opinions. The final HIV infection risk assessment tool
      for MSM has 8 items. Conclusions: The HIV infection risk assessment tool for MSM,
      developed under the Delphi method, can be used in the evaluation of HIV infection
      risk in MSM and individualized prevention and intervention. However, the
      reliability and validity of this risk assessment tool need to be further
      evaluated.

PMID- 29060994
TI  - [Factors affecting the participation rates in epidemiologic surveys].
AB  - Objective: The aim of this study was to investigate the response in health
      related epidemiological investigation among Chinese population aged 15 and over.
      We analyzed the specific causes of non-response, and explored the effective ways
      to improve the response rate, so as to provide reference for future
      epidemiological studies of this kind. Methods: Two modes of studies regarding the
      prevalence of important cardiovascular diseases were used in Chongqing, during
      the 12(th) Five-Year Plan period in oder to find out the cause related to non
      response. Intervention programs were carried out to evaluate the effects.
      Results: When using the concentrated mode (CM), the completion rate to the
      questionnaires was only 20.00% in the pre-investigation, with the response rate
      as 13.48%. In the deconcentrated mode (DM), the completion rate was 31.16%, with
      the response rate as 25.19%. After a series of incentives provided to both the
      respondents and the project-related core staff in the two modes, response rates
      of the two modes increased to the expected 60%. Conclusions: CM appeared having
      advantages on quality control, but was more time consuming, with higher cost, and
      without effective follow-up measures to improve the response rate. However, DM
      had the advantages on controlling the cost and could increase the response rate
      through making advanced appointment with the households but quality control
      remained difficult. Two key points should be strengthened to improve the response
      rates, which including: Precisely finding out the research objects and providing
      incentives to the respondents to attract their interests of participating in the
      investigation.

PMID- 29060995
TI  - [Bias risk assessment: (3) Revised Cochrane bias risk assessment tool for
      individual randomized, cross-over trials (RoB2.0)].
AB  - This paper introduces the revised Cochrane bias risk assessment tool for
      individual randomized, cross-over trials (RoB2.0), comparing RoB2.0 of cross-over
      design with RoB2.0 of parallel design, and illustrating the application of RoB2.0
      for cross-over trials in a published clinical trial. As a comprehensive tool
      specially designed for cross-over design, it provides more information on risk of
      bias in systematic reviews for the evidence synthesis.

PMID- 29060996
TI  - [Screening for precursors of colorectal cancer].
AB  - Screening has been proven to be effective for the control of colorectal cancer
      (CRC). The target of CRC screening is shifting from CRC to colorectal neoplasia
      (CN), the precursors of CRC. Based on the the latest national guideline, the
      Consensus of Screening for CRC and CN, and the recent research of precursors both
      at home and abroad. This paper summarizes the progress in the research of risk
      factors, risk prediction model, screening strategy optimization, colonoscopy
      quality control, sessile serrated adenoma identification and follow up as well as
      the recognition of precursors.

PMID- 29060997
TI  - [Challenges and opportunities for the development of extra-corporeal circulation
      in China].

PMID- 29060998
TI  - [GOLD 2017: Proposals and Questions].

PMID- 29060999
TI  - [GOLD 2017 and clinical practice of COPD in China].

PMID- 29061000
TI  - [Quality control and standardization of extracorporeal circulation].

PMID- 29061001
TI  - [Present status and development of extracorporeal membrane oxygenation].

PMID- 29061002
TI  - [New concepts of extracorporeal circulation management for major vascular
      surgery].

PMID- 29061003
TI  - [The present status and development of cardiopulmonary by pass in infants].

PMID- 29061004
TI  - [Current status and prospect of cardiopulmonary bypass education and training in
      China].

PMID- 29061005
TI  - [Clinical Application Value of Peripheral Blood Diagnostic Report].
AB  - Objective: To explore the clinical application value of peripheral blood
      diagnostic report. Methods: 557 peripheral blood diagnostic reports were
      collected from Peking University First Hospital, YANDA LU DAOPEI Hospital and
      Beijing United Family Hospital. The results were analyzed and summarized
      according to different blood cell morphology character for the first time and
      review cases, respectively. Results: Two hundred and one samples from first time
      patients were found abnormal complete blood count or leukocyte differential
      count, they were summarized as anemia, anemia accompanied with leukopenia or
      thrombopenia, abnormal white blood cell count or leukocyte differential count and
      abnormal platelet count. Each condition was further distinguished on the basis of
      different morphology character. Initial diagnosis or further examination could be
      proposed if abnormal morphology was specific or typical, when blood cell
      morphology was atypical or normal, the morphology was described objectively. 22
      review cases included many benign and malignant disorders such as acute leukemia,
      chronic leukemia, myelodysplastic syndrome, multiple myeloma, infectious
      mononucleosis and so on. Suggestion of therapeutic effect, progression of
      diseases or further examination could be present according to complete blood cell
      count and morphology character. Conclusion: Peripheral blood diagnostic report
      can provide more comprehensive and accurate information for clinic, and propose
      important advisory opinions for primary diagnosis, differential diagnosis,
      treatment monitoring and progression assessment.

PMID- 29061006
TI  - [Efficacy of extended-infusion of carbapenem plus sulbactam for ventilator
      associated pneumonia caused by extensive drug-resistant Acinetobacter baumannii].
AB  - Objective: To evaluate the efficacy of extended-infusion of carbapenem plus
      sulbactam for ventilator-associated pneumonia caused by extensive drug-resistant
      Acinetobacter baumannii (XDRAB). Methods: Clinical data of patients with
      ventilator-associated pneumonia caused by XDRAB who were treated with extended
      infusion carbapenem plus sulbactam or tigecycline-based therapy in Peking
      University First Hospital from January 2015 to December 2016 were collected and
      reviewed in this retrospective study. Twenty-one patients were treated with
      extended-infusion carbapenem plus sulbactam, and 20 other patients received
      tigecycline combined with other antibiotics. The general status of the patient,
      microbiological eradication rate, superinfection rate, new microorganism
      colonization rate, clinical resolution rate on the third day, clinical cure rate
      and mortality during treatment were compared between the two groups. Results: The
      two groups shared similar characteristics except that patients in the carbapenem
      group were younger. Microbiological eradication was not observed. Superinfections
      occurred in 1 patients (4.8%) in the carbapenem group and 0 patients in the
      tigecycline group (P=1.000), the occurrences of new microorganisms colonization
      were 14.3% and 25.0% respectively (P=0.638). Clinical cure were achieved in 57.1%
      of the patients in the carbapenem group and 50.0% of the patients in the
      tigecycline group (P=0.647), the clinical resolution rates on the third day were
      52.4% and 45.0% respectively (P=0.636). The mortality during treatment was 9.5%
      in carbapenem group, and 20.0% in tigecycline group (P=0.612). No serious adverse
      drug reactions occurred. Conclusions: Ventilator-associated pneumonia caused by
      XDRAB treated with either extended-infusion carbapenem plus sulbactam or
      tigecycline-based therapy has a similar clinical outcome.

PMID- 29061007
TI  - [Significance of serum calprotectin in assessing inflammatory bowel disease
      activity].
AB  - Objective: To investigate the application value of serum calprotectin in
      assessing the activity of IBD Methods: Eighty-five Crohn's disease(CD) and eighty
      five Ulcerative colitis(UC) patients at Suzhou Municipal Hospital(North Branch)
      from August 2015 to January 2017 were enrolled in this study, and eighty-five
      healthy subjects were selected as controls. Serum level of calprotectin was
      determined by ELISA. Correlation of serum calprotectin with clinical features of
      IBD was analyzed. The diagnostic efficacy for CD and UC were assessed by ROC
      curve. Results: The level of serum calprotectin was significantly higher in IBD
      patients than in healthy subjects. Positive correlations were found between serum
      calprotectin level and CRP, ESR, fecal calprotectin level of IBD(rho=0.341,
      P<0.001;rho=0.438, P<0.001;rho=0.542, P<0.001,respectively). Besides, positive
      correlations were found between serum calprotectin level with disease activity
      index(CDAI or Mayo score) of IBD(rho=0.309, P=0.004;rho=0.227,
      P=0.036,respectively).Nevertheless, no correlation was found between serum
      calprotectin level with location of IBD and disease subtypes(P>0.05).The area
      under curve(AUC) of serum calprotectin for diagnosis of CD and UC were 0.946 and
      0.906, respectively. Conclusions: Serum level of calprotectin is associated with
      the activity of IBD. As a result,serum level of calprotectin may has the
      potential to be served as a clinical index of IBD activity.

PMID- 29061009
TI  - [Retroperitoneal laparoscopic debridement therapy for infected severe acute
      pancreatitis].
AB  - Objective: To investigate the feasibility and availability of retroperitoneal
      laparoscopic debridement therapy for patients with infected severe acute
      pancreatitis. Methods: Clinical data of 6 patients with severe acute pancreatitis
      who underwent retroperitoneal laparoscopic necrotic tissue debridement therapy in
      the Severe Acute Pancreatitis Center of Sir Run Run Hospital between August 2014
      and October 2015 was retrospectively analyzed. The laparoscopic instruments and
      sponge forceps were used to remove necrotic tissue under retroperitoneal space,
      and double-cavity drainage tube was left for continuous washing. The
      perioperative indicators were collected and analyzed. Results: Two of six
      patients underwent two surgeries, and the others underwent one surgery, with an
      average operation time of (220.0+/-58.3) minutes and a mean hospital stay time of
      62.6 days (35-117 days). One patient underwent re-operation after 33 days because
      of intraperitoneal hemorrhage, and another patient suffered pancreatic pseudocyst
      after the surgery, but no one died in hospital. Conclusion: Retroperitoneal
      laparoscopic debridement therapy is an additional choice for patients with
      infected severe acute pancreatitis, especially for those who had limited necrosis
      under retroperitoneal space. Furthermore, the therapy is in line with the concept
      of minimally invasive surgery and enhanced recovery after surgery.

PMID- 29061008
TI  - [Efficacy and safety of ultrasound-guided or neurostimulator-guided bilateral
      axillary brachial plexus block].
AB  - Objective: To explore the efficacy and safety of bilateral axillary brachial
      plexus block under the guidance of ultrasound or neurostimulator. Methods: From
      February 2012 to April 2014, 120 patients undergoing bilateral hand/forearm
      surgery in Beijing Jishuitan Hospital were enrolled and anaesthetized with
      bilateral axillary brachial plexus block. All patients were divided into two
      groups randomly using random number table: the ultrasound-guided group (group U,
      n=60) and the neurostimulator-guidedgroup (group N, n=60). The block was
      performed with 0.5% ropivacaine. Patients' age, sex and operation duration were
      recorded. Moreover, success rate, performance time, onset of sensor and motor
      block, performance pain, patient satisfaction degree and the incidence of related
      complications were also documented. Venous samples were collected at selected
      time points and the total and the plasma concentrations of ropivacaine were
      analyzed with HPLC. Results: The performance time, the onset of sensor block and
      the onset of motor block of group U were (8.2+/-1.5), (14.2+/- 2.2)and (24.0+/
      3.5)min respectively, which were markedly shorter than those in group N( (14.6+/
      3.9), (19.9+/-3.8), (28.8+/-4.2)min, respectively), and the differences were
      statistically significant(t=11.74, 10.09, 6.73, respectively, all P<0.01). The
      performance pain score of group N was (25.5+/- 13.2), which was obviously more
      serious than group U (31.7+/- 11.2) and a significant statistical difference was
      detected (t=2.856, P<0.05). The patient satisfaction degree of group U was 95.0%,
      which was significantly higher than group N (83.3%) and a markedly statistical
      difference was detected (chi(2)=4.227, P<0.05). Fifty min after performance, the
      total plasma concentration of ropivacaine of group U was(1.76+/-0.48)mg/L, which
      was significantly lower than group N (1.88+/-0.53)mg/L and a significant
      statistical difference was detected (t=2.43, P<0.05), while no significant
      differences were detected at the other time points between two groups (P>0.05).
      No analgesic was superadded and no other anesthesia methods were applied. No
      complications were detected perioperatively. Conclusions: The bilateral axillary
      brachial plexus block under the guidance of ultrasound or neurostimulator are
      both effective and safe for bilateral hand/forearm surgery. However, the
      ultrasound-guided block may be more clinically beneficial because of its shorter
      performance time, rapid onset and higher patient satisfaction degree.

PMID- 29061010
TI  - [Effects of lappaconitine on intraoperative administration of remifentanil
      induced postoperative hyperalgesia in general anaesthesia patients].
AB  - Objective: To explore the effects of lappaconitine on intraoperative
      administration of remifentanil induced postoperative hyperalgesia in general
      anaesthesia patients. Methods: One hundred and twenty patients from March to
      October 2016 undergoing elective thyroid operation under general anaesthesia at
      Ningbo NO.2 hospital, American Society of Anesthesiologists(ASA) I or II grade,
      aged 20-60, were enrolled in this study and randomly assigned to 3 groups (n=40).
      Remifentanil was intraoperatively infused at 0.1 MUg.kg(-1).min(-1) (Group S) or
      0.3 MUg.kg(-1).min(-1) (Groups L and G), and patients in group G received
      lappaconitine 8 mg 30 minutes before the ending of surgery. Mechanical pain
      thresholds, visual analogue scale (VAS) and additional analgesics were recorded
      at 2, 6 and 24 hours after the operation. Results: There was no significant
      difference among the VAS and additional analgesics in three groups at 2, 6 and 24
      h after operation (all P>0.05). There was no significant difference among the
      mechanical pain thresholds in three groups before and 2 h after operation (all
      P>0.05). The mechanical pain thresholds of group S, L and G was (45.7+/-15.6),
      (35.8+/-15.0), (47.6+/-16.4)g at 6 h and (50.7+/-17.0), (33.7+/-14.0), (49.7+/
      13.9 )g at 24 h after operation. There was significant difference among the
      mechanical pain thresholds in group S, L and G at 6 h and 24 h after operation
      (F=6.586, 16.089, all P<0.01). Compared to group S, the mechanical pain
      thresholds significantly decreased in group L at 6 h and 24 h after operation
      (q=2.837, 5.045, all P<0.01). While there was a significantly increase in pain
      thresholds at 6 h and 24 h postoperatively in group G, as compared with the group
      L (q=3.384, 4.770, all P<0.01). Conclusion: Lappaconitine significantly
      alleviated intraoperative administration of remifentanil induced postoperative
      hyperalgesia in general anaesthesia patients.

PMID- 29061012
TI  - [Investigation on the role and mechanism of prostagland in D2 synthase in non
      small cell lung cancer].
AB  - Objective: To investigate prostaglandin D2 synthase (PTGDS) expression in non
      small cell lung carcinoma (NSCLC) and clarify whether PTGDS could be a biomarke.
      Methods: Firstly, the protein expression level of PTGDS in adenocarcinoma (ADC)
      and squamous cell carcinoma (SCC) were analyzed respectively through Gene
      Expression Omnibus (GEO)dataset. Then, the results were verified by using tissue
      microarray (TMA). At last, in order to explore the inner mechanism, lung
      adenocarcinoma cell lines A549 and Calu-3 were selected to over-express PTGDS,
      and then transwell chamber assay and Western blotting were used to detect
      associated changes. Results: PTGDS expression is down-regulated in both ADC and
      SCC, however, no statistical difference has been found between the two groups,
      and PTGDS was only related to the progression of ADC. Furthermore, After over
      expression of PTGDS, the invasiveness of ADC cells was significantly decreased.
      Western blotting showed that the inner mechanisms may be related to mitogen
      activated protein kinase (MAPK) signal pathway. Conclusions: This study revealed
      that PTGDS was down-regulated in NSCLC and only related to the development of
      ADC. It may be a potential biomarker for the diagnosis and prognosis of NSCLC.
      However, whether it could be used for the treatment of NSCLC still needs more
      research.

PMID- 29061011
TI  - [The role of estrogen related-receptor gamma and ATP-dependent K(+) channel Kcnj1
      in renal ischemia-reperfusion injury].
AB  - Objective: To investigate the correlation between estrogen related-receptorgamma
      (ERRgamma) and ATP-dependent K(+) channel Kcnj1 in renal ischemia-reperfusion
      injury and its possible role in regulating ischemic preconditioning. Methods: The
      expression of ERRgamma in kidney tissues was detected by immunohistochemistry.
      The expressions of ERRgamma and Kcnj1 in human renal tubular epithelial cells (HK
      2) under hypoxia (1% O(2)) were detected by RT-PCR. The ERRgamma-deficient
      heterozygous mice model and the ERRgamma-deficient completely mice model were
      established. The pretreatedischemia-reperfusion model were constructed in wild
      type mice, ERRgamma-deficient heterozygous mice and ERRgamma-deficient completely
      mice, respectively. Renal injury was observed under a light microscope with PAS
      staining. ERRgamma and Kcnj1 were tested by immunohistochemistry and RT-PCR.
      Results: ERRgamma in mice kidney tissue was mainly expressed in renal tubules,
      and the expressions of ERRgamma and Kcnj1 were decreased 59% and 29.5%
      respectively after hypoxia in the renal tubular cells (HK-2). In the animal
      model, the expressions of ERRgamma and Kcnj1 were decreased 31.9% and 11% in
      early ischemic mice kidney tubular cells of wild type. The expressions of
      ERRgamma and Kcnj1 in renal tubular cells were decreased 33.2% and 19.1% after
      ischemia and reperfusion. When ERRgamma were overexpressed in renal tubular
      cells, ERRgamma was increased by 89%, and the expression of Kcnj1 was increased
      by 72.5%. The expression of Kcnj1 was decreased by 75.7% in ERRgamma-deficient
      completely mice. However, Kcnj1 expression in renal tissue of ERR-gamma-deficient
      mice was stable, but ischemic preconditioning failed to interfere with renal
      ischemia-reperfusion injury. Conclusion: ERRgamma-Kcnj1 is closely related to
      ischemic preconditioning and protects renal ischemia-reperfusion injury, and may
      be one of the regulatory factors. To explore the protective effect of the
      regulating pathway on ischemia reperfusion injury couldprovide a theoretical
      basis for the development of drug pretreatment.

PMID- 29061013
TI  - [The development of biosimilars in oncology].
AB  - With the extensive application in clinical practice, biological medicine plays a
      significant role in both treatment and supportive care in oncology. With the
      expiration of original drug patents, biosimilars emerge. The biosimilars are
      defined as biological drugs that are be highly similar but not identical to the
      biological reference. Their development and evaluation procedure are different
      from those of small molecular chemical generics. Biosimilars are expected to
      reduce the health care costs worldwide. The booming developments of biosimilars,
      such as rituximab, trastuzumab and bevacizumab in medical oncology can optimize
      the clinical strategies, offer patients more treatment options and reduce the
      medical expenditure. In this article, we review the advances in the field of
      biosimilars, especially focus on the challenges and opportunities of biosimilars
      in clinical oncology.

PMID- 29061014
TI  - [Enhancement of thermal damage to EpCAM-positive tumor cells by novel aptamer
      guided magnetic nanoparticles].
AB  - Objective: To explore the thermal damage to epithelial cell adhesion
      molecule(EpCAM)-positive tumor cells by novel aptamer-guided magnetic
      nanoparticles(AptNPs). Methods: EpCAM aptamer SYL3C was connected to NPs via
      biotin-streptavidin reaction. The diameter of AptNPs were characterized by
      Dynamic Light Scattering(DLS). The binding feature of the aptamer to EpCAM
      positive tumor cells was evaluated by Prussian blue dyeing. Thermal damage under
      alternative magnetic field was measured bylactate dehydrogenase (LDH). The
      apoptosis of EpCAM-positive tumor cells was detected by acridine orange/ethidium
      bromide (AO/EB) double staining. Results: The average size of AptNPs was 282 nm.
      Flow cytometry and Prussian blue dyeing showed that AptNPs exhibited strong
      binding to the EpCAM-positive tumor cells but not to the EpCAM-negative tumor
      cells. Moreover, when incubated with 1.5*10(8) AptNPs under alternative
      electromagnetic fieldfor 5 hours, the viability of EpCAM-positive HCT116 cells
      and A549 cells was 28.9% and 54.4%, respectively, significantly lower than 76.7%
      of EpCAM-negative HepG2 cells (P<0.05). Conclusions: AptNPs can improve the
      thermal damage to EpCAM-positive tumor cells, and may have potential utility in
      the development of tumor targeted therapy.

PMID- 29061015
TI  - [Effectiveness of tyrosine kinase inhibitors against non-small cell lung cancer
      patients with postoperative recurrence harboring uncommon EGFR mutations].
AB  - Objective: To investigate the efficacy of tyrosine kinase inhibitor (TKI)
      treatment on non-small cell lung cancer (NSCLC) patients with postoperative
      recurrence who harbored uncommon EGFR mutations, and discuss the relationship
      between TKI treatment and prognosis. Methods: A total of 39 relapsed NSCLC
      patients after surgery with EGFR uncommon mutations who were detected at Cancer
      Hospital, Chinese Academy of Medical Sciences between January 1999 and December
      2013 were retrospectively analyzed in this study. Twenty patients were treated
      with EGFR-TKI after recurrence and 19 cases were not. The clinical
      characteristics of patients with EGFR uncommon mutations were evaluated, and the
      prognosis of TKI-treatment group and non-TKI treatment group was compared.
      Results: In 39 relapsed NSCLC patients with EGFR uncommon mutations, insertion
      mutations and point mutations were included. The highest frequency of EGFR
      uncommon mutation happened in exon 20 (20/39, 51.3%). A total of 13 uncommon
      point mutations were detected in exon 18, 20 and 21. The most frequent rare point
      mutations located in exon 21, and there were 7 different point mutation sites in
      exon 21. G719S/C/A mutation in exon 18 was the most common type of point mutation
      (14/25, 56.0%). Survival after postoperative recurrence in TKI treatment group
      was obviously better than that in non-TKI treatment group, the median time after
      recurrence were 44 months and 23 months, respectively (P=0.044). However, the
      postoperative overall survival showed no differences between two groups (48
      months vs 43 months, P=0.129). Conclusion: NSCLC patients with postoperative
      recurrence who harbored rare EGFR mutations should be treated with TKI agent.

PMID- 29061016
TI  - [Clinical significance and mechanism of upregulation of PI3Kp110alpha in non
      small cell lung carcinoma].
AB  - Objective: To investigate the clinical significance and mechanism of upregulation
      of phosphoinositide 3-kinase p110alpha(PI3Kp110alpha)in non-small cell lung
      carcinoma (NSCLC). Methods: Expressions of PI3Kp110alpha and other components in
      PI3K signaling pathway (including phospho-Akt (p-Akt, Ser 473), MET, ROS1, HER-2,
      ALK, total EGFR and mutant EGFR) and p53 (the transcription factor of PIK3CA)
      mutation in NSCLC were detected by immunohistochemistry. The relationships
      between PI3Kp110alpha expression and clinicopathological characteristics,
      expressions of other proteins in PI3K pathway and p53 mutation were analyzed.
      Results: In 170 NSCLC patients, 72 cases (42.4%) showed lower expression and 98
      cases (57.6%) showed higher expression of PI3Kp110alpha. Upregulation of
      PI3Kp110alpha was not significantly associated with gender, age, T stage and
      pathologic grade (P>0.05). While upregulation of PI3Kp110alpha was significantly
      associated with smoking status of patients, pathologic classification, N stage,
      TNM stage and Ki-67 index (P<0.05). Expression of PI3Kp110alpha was positively
      correlated with expressions of MET (P<0.05) and mutant EGFR (P=0.018), while not
      significantly related with expressions of p-Akt(Ser473), HER-2, ALK, ROS1, total
      EGFR or p53 mutation (P>0.05). Conclusions: Upregulation of PI3Kp110alpha is
      closely related with tumorigenesis of non-smoking lung adenocarcinoma. MET
      overexpression and EGFR mutation may be crucial to upregulate expression of
      PI3Kp110alpha in NSCLC. Overexpression of PI3Kp110alpha may inhibit tumor cell
      proliferation in NSCLC through a different pathway other than classical PI3K
      pathway. Upregulation of PI3Kp110alpha may predict favorable prognosis of NSCLC
      patients.

PMID- 29061017
TI  - [Impacts of EGFR 19 exon mutations on brain metastases in treatment-naive
      patients with lung adenocarcinoma].
AB  - Objective: To investigate the relationship between the status of epidermal growth
      factor receptor (EGFR) mutations and brain metastases in patients with lung
      adenocarcinoma. Methods: From August 2010 to May 2015, a total of 1 063 lung
      adenocarcinoma patients with identified status of EGFR mutations in Shanxi Cancer
      Hospital were enrolled, of which 456 patients had EGFR mutations. Multivariate
      Logistic regression model was used to analyze the correlation between EGFR
      mutation status and brain metastases in patients with lung adenocarcinoma.
      Results: In 125 patients with brain metastases before initial treatment, 65
      patients had EGFR mutations, including 36 patients with deletion mutations in
      exon 19. The frequency of EGFR 19 exon mutation was 28.8% (36/125). Among 456
      patients with EGFR mutations, 65(14.3%) patients were with brain metastases, in
      which 36(55.0%) had deletion mutations in exon 19. The multivariate analysis
      showed that age, Eastern Cooperative Oncology Group (ECOG) score, EGFR mutations
      and N staging were associated with brain metastases(P<0.05). Further subgroup
      multivariate analyses showed that age, ECOG score, mutation status in exon 19 and
      N staging were associated with brain metastases (P<0.05). Conclusions: EGFR
      mutation status is related to brain metastases. Mutations in EGFR exon 19 is an
      independent risk factor for brain metastases.

PMID- 29061018
TI  - [Prognostic value of three different staging schemes based on pN, MLR and LODDS
      in patients with T3 esophageal cancer].
AB  - Objective: To evaluate the prognostic value of three different staging schemes
      based on positive lymph nodes (pN), metastatic lymph nodes ratio (MLR) and log
      odds of positive lymph nodes (LODDS) in patients with T3 esophageal cancer.
      Methods: From 2007 to 2014, clinicopathological characteristics of 905 patients
      who were pathologically diagnosed as T3 esophageal cancer and underwent radical
      esophagectomy in Zhejiang Cancer Hospital were retrospectively analyzed. Kaplan
      Meier curves and Multivariate Cox proportional hazards models were used to
      evaluate the independent prognostic factors. The values of three lymph node
      staging schemes for predicting 5-year survival were analyzed by using receiver
      operating characteristic (ROC) curves. Results: The 1-, 3- and 5-year overall
      survival rates of patients with T3 esophageal cancer were 80.9%, 50.0% and 38.4%,
      respectively. Multivariate analysis showed that MLR stage, LODDS stage and
      differentiation were independent prognostic survival factors (P<0.05 for all).
      ROC curves showed that the area under the curve of pN stage, MLR stage, LODDS
      stage was 0.607, 0.613 and 0.618, respectively. However, the differences were not
      statistically significant (P>0.05). Conclusions: LODDS is an independent
      prognostic factor for patients with T3 esophageal cancer. The value of LODDS
      staging system may be superior to pN staging system for evaluating the prognosis
      of these patients.

PMID- 29061019
TI  - [Prognostic values of grading system for lymph vessel tumor emboli in patients
      with invasive breast carcinomas of no special type].
AB  - Objective: To investigate the grading system for lymph vessel tumor emboli and
      its prognostic value in patients with invasive carcinomas of no special type
      (ICNST) of the breast. Methods: Clinical data of 466patients with ICNST were
      collected from January 2006 to December 2008 in the Fourth Hospital of Hebei
      Medical University. The expression levels of D2-40, estrogen receptor(ER),
      progesterone receptor(PR) and human epidermal growth factor receptor 2 (HER-2)
      were analyzed using immunohistochemical staining. Grades for lymph vessel
      tumoremboli were classified based on the number of mitotic and apoptotic figures
      in tumor cells under a high-power field. Correlation analysis was performed using
      Spearman rank correlation test. Kaplan-meier curves and Log-rank tests were used
      to analyze the survival rate. Multivariate Cox proportional hazard model was used
      to analyze the prognostic factors. Results: Among the 466 patients, grades for
      lymph vessel tumor emboli were categorized as follows: 280 cases were grade 0
      (60.1%); 112 cases were grade 1 (24.0%); 58 cases were grade 2 (12.5%); 16 cases
      were grade 3 (3.4%). Correlation analyses showed that lymph vessel tumor emboli
      grading system was positively correlated with lymph node metastasis (r=0.365,
      P<0.001). Kaplan-Meier univariant analysis showed that histological grading,
      lymph vessel tumor emboli grading system, lymph node metastasis, the expression
      levels of ER, PR and HER-2 and molecular typing were associated with prognosis of
      patients (P<0.05 for all). Multivariate analysis of Cox proportional hazard model
      showed that lymph vessel tumor emboli grading system and lymph node metastasis
      were independent prognostic factors in patients with ICNST(P<0.05 for all).
      Conclusion: Grading system for lymph vessel tumor emboli canpredict the clinical
      outcome of patients with ICNST.

PMID- 29061020
TI  - [Diagnostic efficacy of (18)F-FDG PET-CT for focal hypermetabolic thyroid
      nodules].
AB  - Objective: To explore the diagnostic efficacy of by (18)F-FDG PET-CT for
      hypermetabolic thyroid nodules. Methods: To retrospectively analyze the clinical
      data of 3 192 patients underwent (18)F-FDG PET-CT in our hospital from May 2012
      to October 2014. Among them, 98 patients were diagnosed with focal hypermetabolic
      thyroid nodules. 61 of the 98 patients were diagnosed with malignant or benign
      thyroid nodules using histopathological or clinical follow-up (22 malignant
      nodules, 39 benign nodules). The average age of these 61 patients was 61.6+/-12.5
      years. Results: The lgSUVmax of malignant group (0.69+/-0.31) was significantly
      higher than that in benign group (0.43+/-0.27) (P=0.001). There was no
      significant difference in age, gender, nodule size, minimum diameter of nodule,
      lgCT, calcification, the boundary definition, density uniformity, and history of
      malignancy between the two groups (P>0.05). Binary Logistic regression indicated
      the AUC of Logistic regressive model(AUC) was 0.866+/-0.049 (95% CI: 0.769
      0.963), and the malignant AUCs of ROC curve was 0.747+/-0.068 (95%CI: 0.614
      0.880) which was only determined by lgSUVmax. The difference was statistically
      significant (P<0.01). Conclusion: (18)F-FDG PET-CT imaging can not only detect
      hypermetabolic thyroid nodules, but also have a certain clinical value for the
      identification of benign and malignant nodules.

PMID- 29061021
TI  - [Dye-tattooing under ultrasound guidance in preoperative localization of neck
      recurrences from thyroid cancer].
AB  - Objective: To evaluate the efficacy and safety of the application of dye
      tattooing under ultrasound guidance in preoperative localization of neck
      recurrences from thyroid cancer. Methods: Between October 2014 to September 2016,
      25 patients with 34 lesions were enrolled. There were 22 cases of papillary
      thyroid carcinoma and three cases of medullary thyroid carcinoma, all of which
      could not be detected by computed tomography. Surgeons located the recurrent
      lesions using dye-tattooing under ultrasound guidance along with radiologist
      three days before the operation. Results: All lesions were successfully located
      (100%), 32 of which were located directly and two of which were located
      indirectly. Postoperative pathological examination confirmed 25 metastases of
      papillary thyroid carcinoma, two metastases of medullary thyroid carcinoma, and
      seven cases of false positives. The accuracy of ultrasound diagnosis was 79.4%.
      After 15 months of follow-up, neither tumor residual nor recurrences was detected
      according to imaging tests. Conclusions: Dye-tattooing under ultrasound guidance
      represents a reliable and safe method for localization of neck recurrences from
      thyroid cancer. The cooperation between experienced surgeons and radiologists
      will be crucial to successful location.

PMID- 29061022
TI  - [Preoperative dynamic contrast-enhanced MRI can reduce the rate of tumor-positive
      resection margins after breast conserving surgery in patients with early non-mass
      breast carcinoma].
AB  - Objective: To investigate the value of preoperative dynamic contrast-enhanced MRI
      in reducing the rate of tumor-positive resection margins after breast conserving
      surgery in patients with early non-mass breast carcinoma. Methods: Seventy-two
      patients with early non-mass breast carcinoma received ultrasonographic and
      mammographic examination and subsequently underwent dynamic contrast-enhanced MRI
      examination before breast conserving surgery. The control group consisted of 74
      patients who had early non-mass breast carcinoma. They only received
      ultrasonographic and mammographic examination and didn't undergo contrast
      enhanced MRI examination. The comparison of the rate of tumor-positive resection
      margins between two groups was performed. The MRI findings that had the
      significant influence on the rate of tumor-positive resection margins were
      analyzed using Logistic regression model. Results: In 28 patients (28/72, 38.9%),
      dynamic contrast-enhanced MRI could correct or supplement the ultrasonographic
      and mammographic findings and resulted in the reasonable change of surgical
      program. The preoperative MRI examination group (n=30) had lower rate of tumor
      positive resection margins than control group for invasive ductal carcinoma
      (23.3% vs 40.0%, P=0.02), but there was no significant difference (21.4% vs
      26.9%, P=0.10) between two groups for ductal carcinoma in situ (n=28). The
      preoperative MRI examination group (n=14) had lower rate of tumor-positive
      resection margins than control group for the other pathologic types of breast
      carcinoma (14.3% vs 38.9%, P=0.02). The statistical analysis on the basis of
      Logistic regression model showed that some main MRI findings, including change
      surrounding the tumor, distance between tumor and nipple and tumor size, had the
      significant influence on the rate of tumor-positive resection margins.
      Conclusion: Preoperative dynamic contrast-enhanced MRI significantly increased
      the accuracy of resection margins evaluation, and greatly reduced the rate of
      tumor-positive resection margins after breast conserving surgery in patients with
      early non-mass breast carcinoma.

PMID- 29061023
TI  - [Exploration of the rational therapeutic regimen for advanced lung cancer
      patients with mild tumor enlargement].
AB  - Objective: To investigate the factors that impacts of therapeutic effect in
      advanced non-small cell lung cancer (NSCLC) patients with mild tumor enlargement
      and the rational therapeutic strategy for them. Methods: The clinicopathological
      features and prognostic data of advanced NSCLC patients whose sum of tumor
      longest diameters with 0 to 20% increase were retrospectively explored, and the
      Cox proportional hazards model was used to analyze the independent prognostic
      factors in patients. Results: The median progression-free survival (PFS) of 54
      patients with the original regimen was 87 days, significantly less than 168 days
      of the median PFS of 49 patients with replacing regimen (P<0.001). The median PFS
      of other chemotherapeutic regiems (154 days) and the targeted therapy (287 days)
      were longer than the origional therapy (P<0.05 for all). The left 7 patients
      received radiotherapy. Receiver operating characteristic (ROC) curve indicated a
      significant difference in the PFS when the maximal cut-off value of tumor
      enlargement ratio was 7%. Univariate analysis of patients with targeted therapy
      after disease progression showed that gender, pathological type, clinical stage,
      lung metastasis and tumor enlargement ratio were the prognostic factors (all of
      P<0.05). Multivariate analysis showed that the tumor enlargement ratio was an
      independent prognostic factor (P=0.001). Single factor analysis showed that the
      chemotherapeutic regimens before and after disease progression were prognostic
      factors of patients received chemotherapy after disease progression (P<0.05). Cox
      multivariate analysis showed that the chemotherapeutic regimen after disease
      progression was an independent prognostic factor of patients (P=0.004). In the
      patients whose tumor enlargement ratio was 0 to 7%, Univariate analysis showed
      that chemotherapeutic regimen before tumor enlargement was a prognostic factor
      (P=0.030), while Cox multivariate analysis showed that it was not an independent
      prognostic factor (P=0.560). In the patients whose tumor enlargement ratio was
      7.1% to 20%, single factor analysis showed that pathological type, bone
      metastasis and chemotherapeutic regimen after disease progression were prognostic
      factors (all of P<0.05), and Cox multivariate analysis showed that all of them
      were independent prognostic factors of these patients (all of P<0.05).
      Conclusions: To the advanced NSCLC patients whose tumor enlargement ratio is 0 to
      20%, the PFS of patients receive replacing regimen is longer than that of
      patients receive original regimen. There is a significant difference in the PFS
      when the maximal cut-off value of tumor enlargement ratio is 7%. To patients
      undergo second-line chemotherapy before disease progression and the tumor
      enlargement ratio is 7.1% to 20%, the PFS of patients receive replacing regimen
      is significantly extended. Dual drug replacing regimen is especially benefit to
      the adenocarcinoma patients without bone metastasis.

PMID- 29061024
TI  - [Comparison of laparoscopic distal pancreatectomy and open distal pancreatectomy
      in pancreatic ductal adenocarcinoma].
AB  - Objective: To compare and evaluate the curative effect of laparoscopic distal
      pancreatectomy(LDP) and traditional open distal pancreatectomy(ODP) in pancreatic
      ductal adenocarcinoma. Methods: The clinical data of 15 patients treated by LDP
      and 87 contemporaneous cases treated by ODP from January 2010 to November 2015
      was collected, and the curative effect and prognosis of these patients were
      retrospectively analyzed. Results: The operation time of LDP group was (286.5+/
      48.1) min, significantly longer than that of OPD group(226.6+/-56.8) min
      (P<0.05). The operative hemorrhage, postoperative exhaust time, recovery eating
      time, the whole and postoperative hospitalization time of LDP group were (188.7+/
      108.9) ml, (2.2+/-1.3) d, (2.9+/-1.1) d, (13.2+/-10.4) d and (9.3+/-8.1) d,
      respectively, dramatically shorter than those of ODP group (625.2+/-982.1) ml,
      (4.3+/-1.7) d, (5.2+/-1.8) d, (20.7+/-8.7) d and (14.9+/-7.8) d, respectively
      (all of P<0.05). There were no intraoperative blood transfusion case in LDP
      group, however, 13 patients in ODP group received intraoperative blood
      transfusion, without significant difference (P=0.207). Alternatively, 6 cases
      occurred pancreatic fistula in LDP group, among them, 5 cases were grade A and 1
      case was grade B; In ODP group, 17 cases occurred pancreatic fistula, among them
      13 cases were grade A, 1 case was grade B and 3 cases were grade C, without
      significant differences (P=0.130). There were 2 cases of delayed gastric empty, 1
      case of pulmonary infection in LDP group. In ODP group, there were 5 cases of
      postoperative delayed gastric empty, 3 cases of pulmonary infection and 6 cases
      of intra-abdominal infection, without significant differences (P>0.05). In both
      LDP group and ODP group, none occurred percutaneous drainage, re-admissions,
      second operation or perioperative death. Conclusions: Compared to ODP, LDP is
      much safer and more steady in perioperative periodand operation. Patients of
      pancreatic ductal adenocarcinoma received LDP can acquire more benefit and
      recovery sooner, and LDP is a safe and effective operative method.

PMID- 29061026
TI  - [Prevention of high-risk complications for high esophagojejunal anastomosis
      leakage after total gastrectomy].

PMID- 29061025
TI  - [Prognostic factors and model of primary liver cancer treated with transcatheter
      arterial chemoembolization combined with radiofrequency ablation].
AB  - Objective: To investigate the prognostic factors of primary liver cancer treated
      with transcatheter arterial chemoembolization (TACE) combined with radiofrequency
      ablation (RFA), and then to establish a prognostic model. Methods:
      Clinicopathological and follow-up data of 145 patients who underwent TACE
      combined with RFA from January 2010 to December 2012 were retrospectively
      analyzed. Univariate and multivariate survival analyses were performed using the
      Cox proportional hazards model, and the prognostic model was established.
      Results: The 1, 2, and 3-year survival rates were 92.6%, 81.4% and 66.2%,
      respectively. The 3-year recurrence and metastasis rate was 64.8%.Multivariate
      analysis showed that female cases and higher serum albumin levels were the
      protective factors for the 3-year overall and relapse-free survival of
      patients(P<0.05 for all). High levels of alpha-fetoprotein (AFP), alanine
      aminotransferase (ALT), total bilirubin (TBIL), portal vein thrombosis and higher
      Child Pugh stages were the independent risk factors for the 3-year overall
      survival(P<0.05 for all). High levels of AFP, TBIL, portal vein thrombosis and
      advanced stages of BCLC staging (B and C) were the independent risk factors for
      tumor recurrence and metastasis(P<0.05 for all). The predictive model established
      based on the multivariate analysis showed good sensitivity and specificity. The
      area under ROC curve were higher than 0.90. Conclusions: The prognosis of liver
      cancer patients treated with TACE combined with RFA is affected by various
      clinicopathological factors. The systematic evaluation of the relevant factors
      before treatment may help to select proper patients and improve prognosis.

PMID- 29061027
TI  - [Lung cancer incidence and mortality in China in 2013].
AB  - Objective: Lung cancer incidence and mortality were estimated by sorting and
      analyzing the national cancer registration data in 2013. Methods: Lung cancer
      data of 2013 were retrieved from the database of 255 qualified cancer registries.
      Lung cancer incidence and mortality rates in cancer registration areas in 2013
      were estimated by areas (urban/rural), gender and age groups, new lung cancer
      cases and deaths were estimated using age-specific rates by areas and gender
      using the corresponding population in 2013. Lung cancer incidence and mortality
      rates in China in 2013 were calculated based on the estimated new cancer cases
      and deaths and the corresponding population. The Chinese population in 2000 and
      Segi's world population were used to calculate age-standardized rates. Results:
      It was estimated that there were about 732.8 thousand new lung cancer cases and
      580.7 thousand deaths occurred in China in 2013. The crude incidence rate was
      53.86/10(5)(males 70.10/10(5,) females 36.78/10(5)), while age-standardized
      incidence rate by Chinese standard populations (ASIRC) and by world standard
      populations (ASIRW) were 36.19/10(5) and 36.09/10(5) with the cumulative
      incidence rate (0-74 years old) of 4.42%.The crude mortality rate was
      43.41/10(5)(males 57.64/10(5,) females 28.45/10(5)), and age-standardized
      mortality rate by Chinese standard populations (ASMRC) and by world standard
      populations (ASMRW) were 28.64/10(5) and 28.41/10(5) with the cumulative
      incidence rate (0-74 years old) of 3.34%.Both incidence and mortality rates were
      higher in males than in females. Crude incidence and mortality rates were
      slightly higher in urban areas than in rural areas, but after age standardized,
      the results were opposite. Conclusions: Lung cancer is the common cancer, which
      both incidence and mortality rates are ranking first in China, and the burden of
      the disease is heavy. Comprehensive measures towards risk factors control, cancer
      early diagnosis and treatment should be strengthened continuously.

PMID- 29061028
TI  - Inhibitory Effects of Panduratin A on Periodontitis-Induced Inflammation and
      Osteoclastogenesis through Inhibition of MAPK Pathways In Vitro.
AB  - Periodontitis is an inflammatory disease caused by microbial lipopolysaccharide
      (LPS), destroying gingival tissues and alveolar bone in the periodontium. In the
      present study, we evaluated the anti-inflammatory and anti-osteoclastic effects
      of panduratin A, a chalcone compound isolated from Boesenbergia pandurata, in
      human gingival fibroblast-1 (HGF-1) and RAW 264.7 cells. Treatment of panduratin
      A to LPS-stimulated HGF-1 significantly reduced the expression of interleukin
      1beta and nuclear factor-kappa B (NF-kappaB), subsequently leading to the
      inhibition of matrix metalloproteinase-2 (MMP-2) and MMP-8 compared with that in
      the LPS control (**p < 0.01). These anti-inflammatory responses were mediated by
      suppressing the mitogen-activated protein kinase (MAPK) signaling and activator
      protein-1 complex formation pathways. Moreover, receptor activator of NF-kappaB
      ligand (RANKL)-stimulated RAW 264.7 cells treated with panduratin A showed
      significant inhibition of osteoclastic transcription factors such as nuclear
      factor of activated T-cells c1 and c-Fos as well as osteoclastic enzymes such as
      tartrate-resistant acid phosphatase and cathepsin K compared with those in the
      RANKL control (**p < 0.01). Similar to HGF-1, panduratin A suppressed
      osteoclastogenesis by controlling MAPK signaling pathways. Taken together, these
      results suggest that panduratin A could be a potential candidate for development
      as a natural anti-periodontitis agent.

PMID- 29061030
TI  - Retracted: DasR, a GntR-family global regulator, regulates N-acetylglucosamine
      metabolism in Streptomyces griseus.

PMID- 29061029
TI  - Neuroprotective and Anti-Neuroinflammatory Activities of Anthraquinones Isolated
      from Photorhabdus temperata Culture Broth.
AB  - Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically
      within entomopathogenic nematodes. The insecticidal compounds derived from
      Photorhabdus are used as biopesticides in agriculture. However, the physiological
      properties are not well characterized. In the course of our screening for
      neuroprotective and anti-neuroinflammatory substances from natural products, the
      culture broth of PT showed considerable activities. By activity-guided
      purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy
      8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8
      dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10
      anthraquinone (5), were isolated from the ethyl acetate fraction of the PT
      culture broth. Among the isolated compounds, 75 uM 3 significantly protected
      mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death
      via the inhibition of reactive oxygen species production, Ca2+ influx, and lipid
      peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-gamma
      induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml,
      via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor
      alpha. Anthraquinones 3 and 4 derived from the PT culture broth are a potential
      starting point to discover neuroprotective and anti-neuroinflammatory drug leads.
      The novel compound 5 is reported for the first time in this study.

PMID- 29061031
TI  - Prolonged Exposure to Lipopolysaccharide Induces NLRP3-Independent Maturation and
      Secretion of Interleukin (IL)-1beta in Macrophages.
AB  - Upon sensing of microbial infections or endogenous danger signals in macrophages,
      inflammasome signaling plays a significant role in triggering inflammatory
      responses via producing interleukin (IL)-1beta. Recent studies revealed that
      active caspase-1, a product of the inflammasome complex, causes maturation of
      inactive pro-IL-1beta into the active form. However, the underlying mechanism by
      which this leaderless cytokine is secreted into the extracellular space remains
      to be elucidated. In this study, we demonstrated that prolonged
      lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected
      maturation and extracellular release of IL-1beta through a nucleotide-binding
      oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)
      independent manner. Short-term treatment (less than 6 h) of LPS induced robust
      production of the IL-1beta precursor form inside cells but did not promote the
      maturation and secretion of IL-1beta in bone marrow-derived macrophages or
      peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to
      a significant release of matured IL-1beta with no robust indication of caspase-1
      activation. Intriguingly, this LPS-triggered secretion of IL-1beta was also
      observed in NLRP3-deficient macrophages. In addition, this unexpected IL-1beta
      release was only partially impaired by a caspase-1 and NLRP3 inflammasome
      inhibitor. Collectively, our results propose that prolonged exposure to LPS is
      able to drive the maturation and secretion of IL-1beta in an NLRP3 inflammasome
      independent manner.

PMID- 29061032
TI  - Immune Effect of Newcastle Disease Virus DNA Vaccine with C3d as a Molecular
      Adjuvant.
AB  - Newcastle disease is a serious infectious disease in the poultry industry. The
      commercial vaccines can only offer limited protection and some of them are
      expensive and need adjuvants. At present, DNA vaccines are widely used. However,
      the immune responses induced by DNA vaccines are too slow and low. Here, we
      constructed the transfer vectors with a different number of C3d as molecular
      adjuvants (n = 1, 2, 4, or 6), and the vectors were cloned into the optimal
      eukaryotic expression plasmid (pVAXI-optiF) that expressed the F gene of
      Newcastle disease virus (NDV), and named pVAXI-F(o)-C3d1, pVAXI -F(o)-C3d2, pVAXI
      F(o)-C3d4, and pVAXI-F(o)-C3d6, respectively. Cell transfection test indicated
      that pVAXI-F(o)-C3d6 showed the highest expression. In vivo immunization showed
      that the chickens immunized with pVAXI-F(o)-C3d6 intramuscularly induced better
      immune responses than the chickens immunized with the other plasmids. The
      protective efficacy of pVAXI-F(o)-C3d6 was 80% after challenge with the highly
      virulent NDV strain F48E9. The results in this study showed that C3d6 could be
      used as a molecular adjuvant to quickly induce an effective immune response to
      control NDV.

PMID- 29061033
TI  - Characteristics of Helicobacter pylori-seropositive subjects according to the
      stool antigen test findings: a prospective study.
AB  - BACKGROUND/AIMS: In countries with a higher risk of gastric atrophic gastritis,
      noninvasive tests are helpful for a more reliable diagnosis of Helicobacter
      pylori infection. The aim of this study was to evaluate the characteristics of
      seropositive subjects according to their stool H. pylori antigen test, serum
      pepsinogen (PG) assay, and endoscopic findings. METHODS: Consecutive subjects who
      visited Konkuk University Medical Center for upper gastrointestinal endoscopy for
      a regular check-up were included in a prospective setting if the serum anti-H.
      pylori immunoglobulin G assay was positive. A H. pylori antigen stool test was
      measured using a stool H. pylori antigen enzyme-linked immunosorbent assay kit on
      the same day as a serum PG assay and endoscopy. RESULTS: Of 318 seropositive
      subjects, 256 (80.5%) showed positive stool test findings. Subjects with a
      negative stool test result showed lower serum PG I (p < 0.001) and PG II (p <
      0.001) levels and higher PG I/II ratio (p < 0.001) than those with a positive
      stool test. Chronic atrophic gastritis was more common in the positive stool test
      group than the negative stool test group on endoscopic finding (p = 0.009). A
      higher serum PG I level (p = 0.001) and a lower serum PG I/II ratio (p = 0.001)
      were independent risk factors for the presence of H. pylori antigen in stool.
      CONCLUSION: A high serum PG level denotes an ongoing current H. pylori infection
      with positive stool H. pylori antigen test findings. Seropositive subjects with
      increased gastric secreting ability tend to have H. pylori in their fecal
      material as reflected by a positive stool H. pylori antigen test finding.

PMID- 29061034
TI  - The Light Cupula: An Emerging New Concept for Positional Vertigo.
AB  - Benign paroxysmal positional vertigo (BPPV) is the most common type of positional
      vertigo. A canalolithiasis-type of BPPV involving the lateral semicircular canal
      (LSCC) shows a characteristic direction-changing positional nystagmus (DCPN)
      which beats towards the lower ear (geotropic) on turning the head to either side
      in a supine position. Because geotropic DCPN in LSCC canalolithiasis is transient
      with a latency of a few seconds, the diagnosis can be challenging if geotropic
      DCPN is persistent without latency. The concept of "light cupula" has been
      introduced to explain persistent geotropic DCPN, although the mechanism behind it
      requires further elucidation. In this review, we describe the characteristics of
      the nystagmic pattern in light cupula and discuss the current evidence for
      possible mechanisms explaining the phenomenon.

PMID- 29061035
TI  - The Effect of Ethnicity on Wideband Absorbance of Neonates with Healthy Middle
      Ear Functions in Malaysia: A Preliminary Study.
AB  - BACKGROUND AND OBJECTIVES: Although ethnicity effect on wideband absorbance (WBA)
      findings was evident for adults, its effect on neonates has not been established
      yet. This study aimed to investigate the influence of ethnicity on WBA measured
      at 0 daPa from neonates with healthy middle ear functions. SUBJECTS AND METHODS:
      Participants were 99 normal, healthy, full-term newborn babies with chronological
      age between 11 and 128 hours of age (mean=46.73, standard deviation=26.36). A
      cross-sectional study design was used to measure WBA at 16 one-third octave
      frequency points from 99 neonates comprising of three ethnic groups: Malays
      (n=58), Chinese (n=13) and Indians (n=28). A total of 165 ears (83.3%) that
      passed a battery of tests involving distortion product otoacoustic emissions, 1
      kHz tympanometry and acoustic stapedial reflex were further tested using WBA.
      Moreover, body size measurements were recorded from each participant. RESULTS:
      The Malays and Indians neonates showed almost identical WBA response across the
      frequency range while the Chinese babies showed lower absorbance values between
      1.25 kHz and 5 kHz. However, the differences observed in WBA between the three
      ethnic groups were not statistically significant (p=0.23). Additionally, there
      were no statistically significant difference in birth weight, height and head
      circumference among the three ethnic groups. CONCLUSIONS: This study showed that
      Malays, Chinese and Indians neonates were not significantly different in their
      WBA responses. In conclusion, to apply for the ethnic-specific norms is not
      warranted when testing neonates from population constitute of these three
      ethnicities.

PMID- 29061036
TI  - Diagnosing ectopic pregnancy in the emergency setting.
AB  - Ectopic pregnancy is the implantation of a fertilized egg outside the uterine
      endometrial cavity. For women presenting to the emergency department with
      abdominal pain and/or vaginal bleeding, ectopic pregnancy is an important
      diagnostic consideration. The diagnosis is made based on laboratory values and
      ultrasound imaging findings. The ultrasound appearance of both normal early
      pregnancy and ectopic pregnancy are variable and often subtle, presenting
      diagnostic challenges for radiologists. This pictorial essay describes and
      illustrates the sonographic findings of ectopic pregnancy and reviews the
      differential diagnoses that can mimic ectopic pregnancy on ultrasound. With the
      possibility of medical management, the value of early detection and prompt
      initiation of treatment has increased in improving clinical outcomes and
      preventing the complications of ectopic pregnancy.

PMID- 29061037
TI  - Highly Porous Silicon Embedded in a Ceramic Matrix: A Stable High-Capacity
      Electrode for Li-Ion Batteries.
AB  - We demonstrate a cost-effective synthesis route that provides Si-based anode
      materials with capacities between 2000 and 3000 mAh.gSi-1 (400 and 600
      mAh.gcomposite-1), Coulombic efficiencies above 99.5%, and almost 100% capacity
      retention over more than 100 cycles. The Si-based composite is prepared from
      highly porous silicon (obtained by reduction of silica) by encapsulation in an
      organic carbon and polymer-derived silicon oxycarbide (C/SiOC) matrix. Molecular
      dynamics simulations show that the highly porous silicon morphology delivers free
      volume for the accommodation of strain leading to no macroscopic changes during
      initial Li-Si alloying. In addition, a carbon layer provides an electrical
      contact, whereas the SiOC matrix significantly diminishes the interface between
      the electrolyte and the electrode material and thus suppresses the formation of a
      solid-electrolyte interphase on Si. Electrochemical tests of the micrometer
      sized, glass-fiber-derived silicon demonstrate the up-scaling potential of the
      presented approach.

PMID- 29061038
TI  - Visualizing Type-II Weyl Points in Tungsten Ditelluride by Quasiparticle
      Interference.
AB  - Weyl semimetals (WSMs) are classified into two types, type I and II, according to
      the topology of the Weyl point, where the electron and hole pockets touch each
      other. Tungsten ditelluride (WTe2) has garnered a great deal of attention as a
      strong candidate to be a type-II WSM. However, the Weyl points for WTe2 are
      located above the Fermi level, which has prevented us from identifying the
      locations and the connection to the Fermi arc surface states by using angle
      resolved photoemission spectroscopy. Here, we present experimental proof that
      WTe2 is a type-II WSM. We measured energy-dependent quasiparticle interference
      patterns with a cryogenic scanning tunneling microscope, revealing the position
      of the Weyl point and its connection with the Fermi arc surface states, in
      agreement with prior theoretical predictions. Our results provide an answer to
      this crucial question and stimulate further exploration of the characteristics of
      WSMs.

PMID- 29061039
TI  - Quantitatively Predictable Control of Cellular Protein Levels through Proteasomal
      Degradation.
AB  - Protein function is typically studied and engineered by modulating protein levels
      within the complex cellular environment. To achieve fast, targeted, and
      predictable control of cellular protein levels without genetic manipulation of
      the target, we developed a technology for post-translational depletion based on a
      bifunctional molecule (NanoDeg) consisting of the antigen-binding fragment from
      the Camelidae species heavy-chain antibody (nanobody) fused to a degron signal
      that mediates degradation through the proteasome. We provide proof-of-principle
      demonstration of targeted degradation using a nanobody against the green
      fluorescent protein (GFP). Guided by predictive modeling, we show that
      customizing the NanoDeg rate of synthesis, rate of degradation, and mode of
      degradation enables quantitative and predictable control over the target's
      levels. Integrating the GFP-specific NanoDeg within a genetic circuit based on
      stimulus-dependent GFP output results in enhanced dynamic range and resolution of
      the output signal. By providing predictable control over cellular proteins'
      levels, the NanoDeg system could be readily used for a variety of systems-level
      analyses of cellular protein function.

PMID- 29061040
TI  - A Circularly Arranged Sextuple Triptycene Gear Molecule.
AB  - Herein we report the synthesis of a circularly arranged sextuple triptycene gear
      molecule, hexakis(10-dodecyloxy-9-triptycyl)ethynylbenzene, via the trimerization
      of the corresponding triyne with a cobalt catalyst. The six triptycene gears are
      closely engaged with each other as confirmed by single crystal X-ray structure
      analysis, and their motion in solution was established by NMR spectroscopy.
      Notably, when one bulky RuCp* complex was attached to one triptycene gear, the
      whole movement of the six gears was highly restricted via their mechanical
      engagement. Development of such a multigear molecule would provide a structural
      basis for molecular motion transmission systems with a switching function.

PMID- 29061042
TI  - Gold Nanoparticles and Radio Frequency Field Interactions: Effects of
      Nanoparticle Size, Charge, Aggregation, Radio Frequency, and Ionic Background.
AB  - In this study, we investigated experimentally the dependency of radio frequency
      (rf) absorption by gold nanoparticles (AuNPs) on frequency (10 kHz to 450 MHz),
      NP size (3.5, 17, and 36 nm), charge of the ligand shell (positive amino and
      negative carboxylic functional groups), aggregation state, and presence of
      electrolytes (0-1 M NaCl). In addition, we examined the effect of protein corona
      on the rf absorption by AuNPs. For the first time, rf energy absorption by AuNPs
      was analyzed in the 10 kHz to 450 MHz rf range. We have demonstrated that the
      previously reported rf heating of AuNPs can be solely attributed to the heating
      of the ionic background and AuNPs do not absorb noticeable rf energy regardless
      of the NP size, charge, aggregation, and presence of electrolytes. However, the
      formation of protein corona on the AuNP surface resulted in rf energy absorption
      by AuNP-albumin constructs, suggesting that protein corona might be partially
      responsible for the heating of AuNPs observed in vivo. The optimal frequency of
      rf absorption for the AuNP-albumin constructs is significantly higher than
      conventional 13.56 MHz, suggesting that the heating of AuNPs in rf field should
      be performed at considerably higher frequencies for better results in vivo.

PMID- 29061041
TI  - Proteomic and Metaproteomic Approaches to Understand Host-Microbe Interactions.

PMID- 29061043
TI  - Simple Rule To Predict Boundedness of Multiexciton States in Covalently Linked
      Singlet-Fission Dimers.
AB  - Because of the potential for increasing solar cell efficiencies, significant
      effort has been spent understanding the mechanism of singlet fission. We provide
      a simple connectivity rule to predict whether the through-bond coupling will be
      stabilizing or destabilizing for the 1(TT) state in covalently linked singlet
      fission chromophores. By drawing an analogy between the chemical system and a
      simple spin-lattice, one is able to determine the ordering of the multiexciton
      spin state via a generalized usage of Ovchinnikov's rule. This allows one to
      predict (without any computation) whether the 1(TT) multiexciton state will be
      bound or unbound with respect to the separated triplets in covalently linked
      singlet-fission dimers. To test our hypothesis, we have performed ab initio
      calculations on a systematic series of covalently linked singlet-fission dimers.
      Numerical examples are given, and the limitations of the proposed theory are
      explored.

PMID- 29061045
TI  - Low-Energy Photoelectron Imaging Spectroscopy of Lan(benzene) (n = 1 and 2).
AB  - Lan(benzene) (n = 1 and 2) are formed in a pulsed laser-ablation molecular beam
      source and characterized by low-energy photoelectron imaging spectroscopy. The
      photoelectron spectrum of La2(benzene) displays a strong origin band, a short
      metal-ligand stretching progression, and a weak ring deformation band. Four
      isomers are considered for La2(benzene), and the preferred structure is an
      inverse sandwich with two La atoms residing on the opposite sides of the benzene
      ring. The ground electronic state of the inverse sandwich is 1A1g (D3d) with
      (5dxy,x2-y2 + pi*)46s2 electron configuration. Ionization removes a La-based 6s
      electron and yields a 2A1g ion. The spectrum of La(benzene) is similar to the
      zero-electron kinetic energy spectrum reported previously by our group, although
      the spectral line width is somewhat broader. The measurement of the photoelectron
      angular distribution of La(benzene) confirms that the ejected electron has
      largely a p wave character. The metal-ligand bonding of La2(benzene) is
      considerably stronger than that of La(benzene) due to the threefold binding of
      each La atom in the dilanthanum species and the twofold binding in the
      monolanthanum complex.

PMID- 29061044
TI  - Ubiquitin Conjugation Probed by Inflammation in Myeloid-Derived Suppressor Cell
      Extracellular Vesicles.
AB  - Ubiquitinated proteins carried by the extracellular vesicles (EV) released by
      myeloid-derived suppressor cells (MDSC) have been investigated using proteomic
      strategies to examine the effect of tumor-associated inflammation. EV were
      collected from MDSC directly following isolation from tumor-bearing mice with low
      and high inflammation. Among the 1092 proteins (high inflammation) and 925
      proteins (low inflammation) identified, more than 50% were observed as
      ubiquitinated proteoforms. More than three ubiquitin-attachment sites were
      characterized per ubiquitinated protein, on average. Multiple ubiquitination
      sites were identified in the pro-inflammatory proteins S100 A8 and S100 A9,
      characteristic of MDSC and in histones and transcription regulators among other
      proteins. Spectral counting and pathway analysis suggest that ubiquitination
      occurs independently of inflammation. Some ubiquitinated proteins were shown to
      cause the migration of MDSC, which has been previously connected with immune
      suppression and tumor progression. Finally, MDSC EV are found collectively to
      carry all the enzymes required to catalyze ubiquitination, and the hypothesis is
      presented that a portion of the ubiquitinated proteins are produced in situ.

PMID- 29061046
TI  - Visual, Label-Free Telomerase Activity Monitor via Enzymatic Etching of Gold
      Nanorods.
AB  - Early diagnosis and life-long surveillance are clinically important to improve
      the long-term survival of cancer patients. Telomerase activity is a valuable
      biomarker for cancer diagnosis, but its measurement often used complex label
      procedures. Herein, we designed a novel, simple, visual and label-free method for
      telomerase detection by using enzymatic etching of gold nanorods (GNRs). First,
      repeating (TTAGGG)x sequences were extented on telomerase substrate (TS) primer.
      It formed G-quadruplex under the help of Hemin and K+. Second, the obtained
      horseradish peroxidase mimicking hemin/G-quadruplex catalyzed the H2O2-mediated
      etching of GNRs to the short GNRs, even to gold nanoparticles (GNPs), generating
      a series of distinct color changes due to their plasmon-related optical response.
      Thus, this enzymatic reaction can be easily coupled to telomerase activity,
      allowing for the detection of telomerase activity based on vivid colors. This can
      be differentiated sensitively by naked eyes because human eyes are more sensitive
      to color variations rather than the optical density variations. As a result,
      telomerase activity can be quantitatively detected ranging from 200 to 15000 HeLa
      cells mL-1. The detection limit was 90 HeLa cells mL-1 (S/N = 3). Importantly,
      the application of this method in bladder cancer samples was in agreement with
      the clinical results. Thus, this method was considerably suitable for point-of
      care diagnostics in resource-constrained regions because of the easy readout of
      results without the use of sophisticated apparatus.

PMID- 29061047
TI  - Construction and Characterization of Broad-Spectrum Promoters for Synthetic
      Biology.
AB  - Characterization of genetic circuits and biosynthetic pathways in different hosts
      always requires promoter substitution and redesigning. Here, a strong, broad
      spectrum promoter, Pbs, for Escherichia coli, Bacillus subtilis, and
      Saccharomyces cerevisiae was constructed, and it was incorporated into the
      minimal E. coli-B. subtilis-S. cerevisiae shuttle plasmid pEBS (5.8 kb). By
      applying a random mutation strategy, three broad-spectrum promoters Pbs1, Pbs2,
      and Pbs3, with different strengths were generated and characterized. These broad
      spectrum promoters will expand the synthetic biology toolbox for E. coli, B.
      subtilis, and S. cerevisiae.

PMID- 29061048
TI  - Surface Coating of Gradient Alloy Quantum Dots with Oxide Layer in White-Light
      Emitting Diodes for Display Backlights.
AB  - Recently, quantum dots (QDs) have been successfully developed as efficient color
      converters for light-emitting diodes (LEDs) display due to excellent optical
      properties of QDs. Herein, we demonstrate a new approach to form metal oxide
      layers (or metal oxide coating) on the exterior surface of gradient alloy QDs
      (the most advanced chemical architecture QDs developed thus far wherein the
      lattice parameter from the core to shell is changing in a gradient fashion) in
      order to improve the photochemical stability and photoluminescence efficiency.
      The resulting CdO-treated QDs are incorporated into polymer matrix films to
      fabricate a backlight unit as a part of display panel wherein CdO-treated
      gradient alloy QDs are utilized as color converters upon the blue-LED excitation.
      The fabricated 9.7 in. iPad 2 tablet liquid crystal display panel exhibited an
      excellent uniformity in terms of CIE chromaticity, luminance, and bright
      variation and superb durability test results (maintenance of ca. 110% brightness
      compared to initial value even after 3 weeks of operation).

PMID- 29061049
TI  - Complementary Imaging of Silver Nanoparticle Interactions with Green Algae: Dark
      Field Microscopy, Electron Microscopy, and Nanoscale Secondary Ion Mass
      Spectrometry.
AB  - Increasing consumer use of engineered nanomaterials has led to significantly
      increased efforts to understand their potential impact on the environment and
      living organisms. Currently, no individual technique can provide all the
      necessary information such as their size, distribution, and chemistry in complex
      biological systems. Consequently, there is a need to develop complementary
      instrumental imaging approaches that provide enhanced understanding of these "bio
      nano" interactions to overcome the limitations of individual techniques. Here we
      used a multimodal imaging approach incorporating dark-field light microscopy,
      high-resolution electron microscopy, and nanoscale secondary ion mass
      spectrometry (NanoSIMS). The aim was to gain insight into the bio-nano
      interactions of surface-functionalized silver nanoparticles (Ag-NPs) with the
      green algae Raphidocelis subcapitata, by combining the fidelity, spatial
      resolution, and elemental identification offered by the three techniques,
      respectively. Each technique revealed that Ag-NPs interact with the green algae
      with a dependence on the size (10 nm vs 60 nm) and surface functionality (tannic
      acid vs branched polyethylenimine, bPEI) of the NPs. Dark-field light microscopy
      revealed the presence of strong light scatterers on the algal cell surface, and
      SEM imaging confirmed their nanoparticulate nature and localization at nanoscale
      resolution. NanoSIMS imaging confirmed their chemical identity as Ag, with the
      majority of signal concentrated at the cell surface. Furthermore, SEM and
      NanoSIMS provided evidence of 10 nm bPEI Ag-NP internalization at higher
      concentrations (40 MUg/L), correlating with the highest toxicity observed from
      these NPs. This multimodal approach thus demonstrated an effective approach to
      complement dose-response studies in nano-(eco)-toxicological investigations.

PMID- 29061051
TI  - Ultrathin Oxide Layer-Wrapped Noble Metal Nanoparticles via Colloidal
      Electrostatic Self-Assembly for Efficient and Reusable Surface Enhanced Raman
      Scattering Substrates.
AB  - Controllable and flexible fabrication of ultrathin and uniform oxide layer
      wrapped noble metal nanoparticles (NPs) has been expected. Here a new strategy is
      presented for them based on colloidal electrostatic attraction and self-assembly
      on the metal NPs via one-step laser ablation of noble metal targets in the
      hydrolysis-induced hydroxide sol solutions at room temperature. The Au NPs, with
      several tens of nanometers in size, are taken as core part and TiO2 as shell
      layer to demonstrate the validity of the presented strategy. It has been shown
      that the TiO2 shell-wrapped Au NPs are obtained after laser ablation of Au target
      in the hydrolysis-induced Ti(OH)4 sol solution. The Au NPs are about 35 nm in
      mean size, and the TiO2 shell layers are amorphous in structure and about 2.5 nm
      in thickness. The shell thickness is nearly independent of the Au NPs' size.
      Further experiments have shown that the thickness and crystallinity of the shell
      layer can be tuned and controlled via changing the temperature or pH value of the
      Ti(OH)4 sol solution or prolonging the laser ablation duration. The formation of
      the TiO2 shell-wrapped Au NPs is attributed to attachment and self-assembly of
      Ti(OH)4 colloids on the laser-induced Au NPs due to the electrostatic attraction
      between them. Importantly, the presented strategy is universal and suitable for
      fabrication of many other ultrathin oxide-wrapped noble metal NPs. A series of
      oxide shell-wrapped noble metal NPs have been successfully fabricated, such as
      Au@oxides (Fe2O3, Al2O3, CuO, and ZnO) as well as Pt@TiO2 and Pd@TiO2, etc.
      Further, compared with the pure gold NPs-built film, the TiO2-wrapped Au NPs
      built film has exhibited much stronger surface enhanced Raman scattering (SERS)
      performance to the anions NO3-, which weakly interact with noble metals, and the
      good reusability for the SERS-based detection of 4-nitrophenol, which could be
      photodegraded by xenon lamp irradiation. This work provides a flexible and
      universal route to the ultrathin and uniform oxide layer-wrapped noble metal NPs.

PMID- 29061050
TI  - Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA-b-PNIPAAm Nanogels
      for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug
      Resistant Breast Cancer Cells.
AB  - The tumor microenvironments are often acidic and overexpress specific enzymes. In
      this work, we synthesized a poly(AA-b-NIPAAm) copolymer (PAA-b-PNIPAAm) using a
      reversible addition-fragmentation chain transfer (RAFT) polymerization method.
      PAA-b-PNIPAAm and a cationic protein (protamine) were self-assembled into
      nanogels, which effectively reduced the cytotoxicity of protamine. The
      protamine/PAA-b-PNIPAAm nanogels were responsive to the stimuli including
      temperature, pH, and enzyme due to disaggregation of PAA-b-PNIPAAm, change in
      random coil/alpha-helix conformation of protamine, and enzymatic hydrolysis of
      the protein. Changing the pH from 7.4 to a lowered pHe (6.5-5.0) resulted in an
      increase in mean particle size and smartly converted surface charge from negative
      to positive. The cationic nanogels easily passed through the cell membrane and
      enhanced intracellular localization and accumulation of doxorubicin-loaded
      nanogels in multidrug resistant MCF-7/ADR breast cancer cells. Cold shock
      treatment triggered rapid intracellular release of doxorubicin against P
      glycoprotein (Pgp)-mediated drug efflux, showing significantly improved
      anticancer efficacy as compared with free DOX. Furthermore, the nanogels were
      able to carry a rose bengal photosensitizer and caused significant damage to the
      multidrug resistant cancer cells under irradiation. The cationic nanogels with
      stimuli-responsive properties show promise as drug carrier for chemotherapy and
      photodynamic therapy against cancers.

PMID- 29061052
TI  - Conserving Coherence and Storing Energy during Internal Conversion: Photoinduced
      Dynamics of cis- and trans-Azobenzene Radical Cations.
AB  - Light harvesting via energy storage in azobenzene has been a key topic for
      decades and the process of energy distribution over the molecular degrees of
      freedom following photoexcitation remains to be understood. Dynamics of a
      photoexcited system can exhibit high degrees of nonergodicity when it is driven
      by just a few degrees of freedom. Typically, an internal conversion leads to the
      loss of such localization of dynamics as the intramolecular energy becomes
      statistically redistributed over all molecular degrees of freedom. Here, we
      present a unique case where the excitation energy remains localized even
      subsequent to internal conversion. Strong-field ionization is used to prepare cis
      and trans-azobenzene radical cations on the D1 surface with little excess energy
      at the equilibrium neutral geometry. These D1 ions are preferably formed because
      in this case D1 and D0 switch place in the presence of the strong laser field.
      The postionization dynamics are dictated by the potential energy landscape. The
      D1 surface is steep downhill along the cis/trans isomerization coordinate and
      toward a common minimum shared by the two isomers in the region of D1/D0 conical
      intersection. Coherent cis/trans torsional motion along this coordinate is
      manifested in the ion transients by a cosine modulation. In this scenario, D0
      becomes populated with molecules that are energized mainly along the cis-trans
      isomerization coordinate, with the kinetic energy above the cis-trans
      interconversion barrier. These activated azobenzene molecules easily cycle back
      and forth along the D0 surface and give rise to several periods of modulated
      signal before coherence is lost. This persistent localization of the internal
      energy during internal conversion is provided by the steep downhill potential
      energy surface, small initial internal energy content, and a strong hole-lone
      pair interaction that drives the molecule along the cis-trans isomerization
      coordinate to facilitate the transition between the involved electronic states.

PMID- 29061053
TI  - Air/Liquid Interfacial Nanoassembly of Molecular Building Blocks into
      Preferentially Oriented Porous Organic Nanosheet Crystals via Hydrogen Bonding.
AB  - Nanosheets with highly regulated nanopores are ultimately thin functional
      materials for diverse applications including molecular separation and detection,
      catalysis, and energy conversion and storage. However, their availability has
      hitherto been restricted to layered parent materials, covalently bonded sheets,
      which are layered via relatively weak electrostatic interactions. Here, we report
      a rational bottom-up methodology that enables nanosheet creation beyond the
      layered systems. We employ the air/liquid interface to assemble a
      triphenylbenzene derivative into perfectly oriented highly crystalline
      noncovalent-bonded organic nanosheets under ambient conditions. Each molecular
      building unit connects laterally by hydrogen bonding, endowing the nanosheets
      with size- and position-regulated permanent nanoporosity, as established by in
      situ synchrotron X-ray surface crystallography and gas sorption measurements.
      Notably, the nanosheets are constructed specifically by interfacial synthesis,
      which suppresses the intrinsic complex interpenetrated structure of the bulk
      crystal. Moreover, they possess exceptional long-term and thermal stability and
      are easily transferrable to numerous substrates without loss of structural
      integrity. Our work shows the power of interfacial synthesis using a suitably
      chosen molecular component to create two-dimensional (2D) nanoassemblies not
      accessible by conventional bulk crystal exfoliation techniques.

PMID- 29061054
TI  - Preface to the Tribute to Keith E. Gubbins, Pioneer in the Theory of Liquids
      Special Issue.

PMID- 29061055
TI  - Neutrophil-to-lymphocyte ratio as a predictor of preoperative tumor staging in
      testicular germ cell tumors.
AB  - OBJECTIVES: The aim of our study was to evaluate associations of elevated
      preoperative neutrophil-to-lymphocyte ratio (NLR) with testicular germ cell
      tumors (GCT) characteristics other than cancer specific survival (CSS) and
      progression free survival (PFS). BACKGROUND: NLR was recently presented as a
      widely available and inexpensive marker of poor prognosis in several types of
      solid tumors. Previous study showed no predictive value of NLR for CSS and PFS in
      testicular GCT. METHODS: Association of high NLR with histological type of tumor,
      presence of metastatic disease preoperatively and worse than T1 stadium in TNM
      classification preoperatively was analyzed in 103 patients who underwent radical
      orchiectomy for testicular GCT. RESULTS: No statistically significant difference
      in the prevalence of seminomas and non-seminomas neither in the group with NLR>=4
      (p=0.6698) nor in the group with NLR<4 (p=0.9115) was detected. Similarly, no
      statistically significant difference in the prevalence of metastatic and non
      metastatic disease in the group with NLR>=4 (p=0.2008), however statistically
      significant higher prevalence of non-metastatic disease in the group with NLR<4
      (p=0.0001) was found. There was a statistically significant higher number of
      patients with worse than T1 stadium in patients with NLR>=4 (p=0.0105), but not
      significant difference in the group with NLR<4 (p=0.0956). CONCLUSION: The
      results of our study showed that NLR lower than 4 predicts non-metastatic disease
      and NLR higher or equal 4 predicts worse than T1 stadium (Tab. 3, Ref. 12).

PMID- 29061056
TI  - Value of neutrophil to lymphocyte and platelet to lymphocyte ratios in pneumonia.
AB  - PURPOSE: In our study, we aimed to evaluate neutrophil to lymphocyte ratio (NLR)
      and platelet to lymphocyte ratio (PLR) in patients with Community-acquired
      pneumonia (CAP). METHODS: This is a retrospective study consisting of 114
      patients with CAP and 50 control subjects. Patients with CAP were divided into 2
      groups, as inpatient and outpatient. RESULTS: The main findings of our study were
      that NLR, PLR and CRP levels were significantly higher in CAP than those in the
      control group. These biomarkers were also higher in inpatient group than
      outpatient group, but not statistically significant. CONCLUSION: To our
      knowledge, this is the first study which investigated the role of NLR and PLR as
      inflammatory biomarkers and the difference in inpatients and outpatients with CAP
      and their correlation with CRP values in children. However, larger prospective
      studies are needed to establish their utility as a predictor for the presence of
      CAP (Tab. 1, Fig. 2, Ref. 9).

PMID- 29061057
TI  - Analysis of HLA-G gene polymorphisms in Slovak women with pre-eclampsia.
AB  - OBJECTIVES: To identify possible association between the selected HLA-G gene
      polymorphisms and risk of pre-eclampsia. BACKGROUND: Pre-eclampsia is a serious
      multisystem disorder that affects women during pregnancy. Despite many research
      studies, the pathology of pre-eclampsia is not fully understood. Human leukocyte
      antigen G (HLA-G) belongs to the molecules that induce fetal acceptance by the
      maternal immune system. HLA-G expression was found to be impaired in the women
      suffering from pre-eclampsia suggesting its involvement in the development of pre
      eclampsia. METHODS: 123 women with pre-eclampsia and 102 women with normotensive
      pregnancy were included in the study. HLA-G gene polymorphisms affecting its
      expression was determined, namely the HLA-G 14 bp insertion/deletion polymorphism
      in the 3'UTR and HLA-G 1597DeltaC polymorphism tagging the HLA-G*01:05N null
      allele. Genotyping was performed by PCR and PCR-RFLP. RESULTS: No statistically
      significant differences in either allele or genotype frequencies between pre
      eclampsia cases and control group have been observed (p > 0.05). CONCLUSION:
      Genetic predisposition of HLA-G to pre-eclampsia in Slovak women was examined for
      the first time. No association between analysed HLA-G gene polymorphisms and
      susceptibility to pre-eclampsia was observed. Further investigations are needed
      to determine the role of immunosuppressive molecule HLA-G in pre-eclampsia
      development (Tab. 5, Fig. 2, Ref. 37).

PMID- 29061059
TI  - Bone metastases in neuroendocrine tumors.
AB  - Neuroendocrine tumors arise from various cells that form a part of the endocrine
      system and account for a small number of cases encountered by oncologists in
      clinical practice. The clinical incidence of these tumors used to be low, and
      newer imaging modalities have now begun to be used for detecting bone metastases
      at an earlier stage. Bone metastases arising from neuroendocrine tumors are a
      well-recognized complication. Their presence carries along a poor prognosis.
      Clinical symptoms are similar to those encountered in other forms of cancer that
      are complicated by bone metastasis. Over the last decade or so, the clinical
      detection, diagnostic methods and treatment strategies have changed dramatically,
      and new treatments are emerging slowly. The indolent course of neuroendocrine
      tumors and the development of bone metastasis have limited our current knowledge
      on how to best prevent and manage the condition. Current information available
      from clinical studies is marred by paucity and small sample sizes, making further
      clinical trials an absolute necessity. In this review, we discuss the current
      status in the diagnosis and management of bone metastases arising from
      neuroendocrine tumors (Fig. 3, Ref. 28).

PMID- 29061058
TI  - The significance of miR-145 in the prediction of preeclampsia.
AB  - AIM: The aim of this study was to explain the effects of miRNA-145 in the
      pathogenesis of preeclampsia. METHODS: Collecting the placental tissue of 40
      severe preeclampsia patients and 20 normal pregnant women, and observation of the
      pathological findings by HE staining. Measuring the miR-145 by RT-PCR. EVCT were
      divided into NC group; MC group and miRNA group. The EVCT cells of MC and miRNA
      groups were simulated by hypoxia in vivo by CoCl2. Measuring the proliferation
      rate of different groups by MTT testing. The cells apoptosis rates were measured
      by flow cytometry; evaluating PI3K, Akt, mTOR and P53 gene and protein expression
      of three groups by RT-PCR and WB. RESULTS: Compared to the normal pregnant
      placental tissue. The miR-145 expression of preeclampsia pregnant placental
      tissue was significantly decreased (p < 0.05). In the cell experiments, the
      proliferation rate was significantly increased, and the cell apoptosis rate was
      significantly reduced in MC group compared to the MC group (p<0.05,
      respectively). Comparing with MC group, the PI3K, Akt and mTOR gene and protein
      expression of miRNA group were significantly up-regulated and the P53 expression
      was significantly down-regulated (p<0.05, respectively). CONCLUSION: miR-145
      might have effects to predict preeclampsia via PI3K/Akt/mTOR signalling pathways
      (Fig. 5, Ref. 30).

PMID- 29061060
TI  - Relationship between ncRNAs and gastric cancer: meta-analysis.
AB  - OBJECTIVE: This study was designed to investigate the action and mechanism of
      cordyceps polysaccharide on rat acute liver failure (ALF). METHODS: Sixty rats
      were randomly divided into five groups: normal group, model group, and cordyceps
      polysaccharide groups with high, middle and low doses (20, 10 and 5 mg/ml).
      Apoptosis was detected through TUNEL method. Protein expressions of caspase 1, IL
      18, IL-10, VEGF, and SDF-1alpha in liver tissue are detected by Western Blot.
      PCNA and sIRPalpha1 contents were measured by PCR method. Rat ALF is modeled with
      a D-galactosamine induced by lipopolysaccharide (LPS). RESULTS: The results after
      modelling showed tissue HE staining wiith typical manifestation of acute liver
      injury. Compared with the medicated group, serum ALT and AST, as well as
      hepatocyte apoptosis are significantly higher in the liver failure group, in a
      time-dependent way. This suggests that medication can effectively inhibit the
      expression of caspase 1, IL-18, and IL-10, while simultaneously increasing the
      expression of VEGF and SDF-1alpha, as well as of PCNA and sIRPalpha1. Cordyceps
      polysaccharide can alleviate the immune inflammatory response in acute liver
      failure, and may be specifically homing to the damaged liver, thus promoting the
      secretion of VEGF, proliferation of hepatocyte, regeneration of liver vessels,
      and repair of liver tissues. CONCLUSION: Medication can reduce the IL-10 level,
      regulate the equilibrium of pro-inflammatory and anti-inflammatory factors, and
      decrease the level of caspase 1 and IL-18 (Tab. 2, Fig. 1, Ref. 18).

PMID- 29061061
TI  - Metabolic disturbances induce malignant heart arrhythmias in rats.
AB  - OBJECTIVES: Metabolic disturbances are considered to condition the occurrence of
      malignant heart arrhythmias and negatively influence the chances of a patient to
      survive. To test this assumption, a model of metabolic syndrome was selected in
      which rats were receiving a diet resembling that of the westernized population.
      BACKGROUND: Metabolic syndrome is a comorbidity of major cardiovascular risk
      factors (dyslipidemia, hypertension, impaired glucose tolerance or insulin
      resistance, diabetes mellitus, and obesity), all facilitating cardiovascular
      complications leading to morbidity and mortality of patients. METHODS: Hearts
      were isolated and perfused according to Langendorff. Global ischemia was induced
      in the hearts and arrhythmia occurrence in reperfusion was monitored. All hearts
      were stimulated with the electro-cardio-stimulator to test the electrical
      inducibility of heart arrhythmia. RESULTS: Isolated hearts from rats with the
      metabolic syndrome were more susceptible to ventricular arrhythmias. The high-fat
      diet increased the occurrence of malignant heart arrhythmias in rats with
      metabolic syndrome to an even greater extent. All subjects with metabolic
      syndrome were sensitive to ventricular tachyarrhythmia with significantly
      decreased threshold to its induction in cardio-stimulation. CONCLUSIONS: These
      results indicate that metabolic syndrome patients may be more sensitive to the
      occurrence of malignant heart arrhythmias following myocardial infarction or
      other heart diseases (Tab. 1, Fig. 2, Ref. 34).

PMID- 29061062
TI  - Clinical and histopathological relationship of sildenafil and bosentan treatments
      in rats with monocrotaline induced pulmonary hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a challenging disorder
      characterized by increasing pulmonary artery pressure, which is hard to treat.
      OBJECTIVE: This study was aimed to investigate the effects of bosentan,
      sildenafil and their combination. METHODS: Saline or MCT were applied to Wistar
      rats. By the development of PAH (4th week), MCT-given rats were treated orally
      with bosentan, sildenafil and combination of sildenafil and bosentan or placebo.
      ECHO examinations were performed. Tissues obtained from all of the rats were
      evaluated under an electron microscope. RESULTS: Left ventricular end diastolic
      diameter significantly increased in sildenafil and combined groups. Sildenafil
      group revealed a significant decrease in RV pressure and wall thickness.
      Examination of lung revealed a significant amount of connective tissue formation
      and increase in inflammatory cells in all the groups except controls in the
      interalveolar septum. Examination of PA revealed an increase in connective tissue
      volume, hypertrophic changes and expansions in granular endoplasmic reticulum
      cisternaes in smooth muscle cells in active groups rather than in the controls.
      Unlike the controls, the examination of the RV revealed an enlargement of the
      sarcoplasmic reticulum cisternaes in some cells, due to the calcium increase.
      CONCLUSION: Sildenafil and the combined therapy demonstrated to have more impact
      on pressure and the RV parameters in rats, with lower inflammatory findings in
      lung tissue (Fig. 6, Ref. 31).

PMID- 29061063
TI  - Effects of N-acetyl cysteine to improve acute lung injury in rats.
AB  - AIM: To study the mechanism of NAC to improve LPS induced acutelung lung injury.
      METHODS: The 40 rats were divided into 4 groups included NC group, Model group,
      NAC group and DXM group. The rats of Model, NAC and DXM groups were injected LPS,
      NAC group and DXM group were resepectively injected NAC (200 mg/kg) or DXM (70
      mg/kg). Collecting the bronchoalveolar lavage fluid (BALF) from lung, and
      measuring the TGF-beta1 concentration of BALF and lung tissue in 4 groups; After
      executing the rats, taken the lung tissue to observant lung pathological
      morphology and evaluated TGF-beta1 expression of difference groups. Measuring the
      TLR-4 and NF-kappab in 4 groups by WB assay. RESULTS: Compared with Model group,
      The NAC and DXM groups were improved in H (et) E staining, the TGF-beta1
      concentration of NAC and DXM groups were significantly reduced in BALF and lung
      tissue (p < 0.05, respectively). TLR-4 and NF-kappab proteins of NAC and DXM
      groups were lower than that of Model group in IHC and WB assays (p < 0.05,
      respectively). CONCLUSION: NAC had effects to protect LPS induced lung injury via
      TLR-4/NF-kappab signaling pathway (Fig. 5, Ref. 19).

PMID- 29061064
TI  - Protective effect of ischemic preconditioning on testis injury following
      transient focal cerebral ischemia in diabetic rats.
AB  - OBJECTIVES: We aim to evaluate the effect of ischemic preconditioning (IPreC) on
      testicular tissue after transient middle cerebral artery occlusion (MCAo) in
      Streptozotocin-induced diabetic (STZ) and non-diabetic rats. METHODS: Testis
      injury and alterations of testosterone levels were evaluated histologically..
      Testicular damage was detected by using hematoxylin- eosin and periodic acid-
      schiff staining and apoptosis was identified by terminal-deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: Total mean serum
      testosterone levels decreased in all diabetic groups (p < 0.05) although remote
      ischemia and IPreC did not have any effect. Serious testicular tubular damage was
      observed in both, diabetic and ischemic groups (p 0.05). Otherwise, remote IPreC
      induced MNAC instead of any changes in histopathological architecture. Moreover,
      remote IPreC reduced the tubular degeneration against synergistic damage of both
      ischemia and diabetes (p < 0.05). CONCLUSIONS: It can be suggested that remote
      ischemic preconditioning prevents testicular damage by improving
      histopathological alterations and inducing apoptosis, probably temporarily, after
      focal transient middle cerebral artery occlusion in both, diabetic and non
      diabetic rats. This is the first report demonstrating protective effects of
      ischemic preconditioning on remote testis injury after transient middle cerebral
      artery occlusion in diabetic rats (Fig. 6, Ref. 23).

PMID- 29061066
TI  - Celiac disease and hearing loss.

PMID- 29061065
TI  - Improving the potency of DNA vaccine encoding HIV-1 Nef antigen using two
      endogenous adjuvants in mouse model.
AB  - BACKGROUND: DNA immunization can induce long-term immune responses, which are
      required to design an effective HIV vaccine. It was shown that antigen-expressing
      plasmids can increase the protective immunity against infectious diseases such
      as: influenza and malaria. However, DNA-based immunizations have poor
      immunogenicity, thus the use of potent immunoadjuvants can enhance their potency.
      METHODS: In the current study, preparation of the recombinant HIV-1 Nef, Gp96 and
      HMGB1 DNA constructs was performed in bacterial system. Then, the immunogenicity
      of DNA construct harboring HIV-1 Nef gene (pcDNA-Nef) was studied using two
      endogenous adjuvants (pcDNA-HMGB1 and pcDNA-Gp96) in BALB/c mouse model. RESULTS:
      Our data showed that co-injection of pcDNA-Nef with pcDNA-HMGB1 effectively
      raised both humoral and cell-mediated immune responses in mice as compared to
      pcDNA-Nef adjuvanted with pcDNA-gp96. Indeed, co-immunization of HIV-1 Nef DNA
      with HMGB1 DNA significantly induced high levels of IgG2a and IFN-gamma directed
      toward Th1 responses and also cytotoxic T lymphocytes (CTLs) activity in
      comparison with other immunized groups. CONCLUSION: These findings suggest that
      the full length of HMGB1 gene could be a more efficient adjuvant for improvement
      of therapeutic HIV DNA-based immunization compared to the full length of gp96
      gene (Tab. 1, Fig. 3, Ref. 58).

PMID- 29061067
TI  - The Structure of Psychopathology in Early Adolescence: Study of a Canadian
      Sample: La structure de la psychopathologie au debut de l'adolescence: etude d'un
      echantillon canadien.
AB  - OBJECTIVE: The current study investigates the correlational structure of
      psychopathology in a large sample of Canadian adolescents and highlights the
      association between the psychopathological dimensions and gender. METHOD: Data
      came from 3826 Canadian adolescents aged 12.8 +/- 0.4 y. Five alternative
      dimensional models were tested using confirmatory factor analysis, and the
      association between gender, language, and the mean level of psychopathological
      dimensions was examined using a multiple-indicators multiple-causes model.
      RESULTS: A bifactor model with 1 general psychopathology factor and 3 specific
      dimensions (internalizing, externalizing, thought disorder) provided the best fit
      to the data. Results indicated metric invariance of the bifactor structure with
      respect to language. Females reported higher mean levels of internalizing, and
      males reported higher mean levels of externalizing. No significant sex
      differences emerged in liability to thought disorder or general psychopathology.
      The presence of a general psychopathology factor increased the association
      between gender and specific dimensions. CONCLUSIONS: The current study is the
      first to highlight the bifactor structure including a specific thought disorder
      factor in a Canadian sample of adolescents. The findings further highlight the
      importance of transdiagnostic approaches to prevention and intervention among
      young adolescents.

PMID- 29061068
TI  - Three-Layer Two-Step Posterior Reconstruction Using Peritoneum During Robot
      Assisted Radical Prostatectomy to Improve Recovery of Urinary Continence: A
      Prospective Comparative Study.
AB  - INTRODUCTION: We present our experience with a novel three-layer two-step
      posterior reconstruction (PR) technique using peritoneum during robot-assisted
      radical prostatectomy (RARP) to improve recovery of postoperative urinary
      continence. METHODS: Forty-eight patients with localized prostate cancer were
      enrolled in this study and were divided randomly into two groups, which were
      treated by the standard PR technique (standard PR group; n = 24) or the three
      layer PR technique using peritoneum (three-layer PR group; n = 24) during RARP.
      We prospectively analyzed the continence rate by the 1-hour pad test. All
      patients underwent urethrocystography at 6 days postoperatively to evaluate
      position of vesicourethral junction. Pelvic MRI was also performed at 6 months
      postoperatively for anatomical evaluation. RESULTS: Four weeks after RARP, the
      urinary continence rate was significantly higher in the three-layer PR group
      (57%) than in the standard PR group (26%, p = 0.036). Urethrocystography
      demonstrated that the postoperative craniocaudal distance from the symphysis
      pubis to the level of the vesicourethral junction was significantly shorter in
      the three-layer PR group than in the standard PR group (p < 0.01), suggesting
      that there was less tension on the vesicourethral anastomosis after three-layer
      PR. MRI confirmed that three-layer PR provided firmer reinforcement of the
      structures, supporting the posterior aspect of the urethral sphincter complex.
      CONCLUSIONS: This prospective comparative study might suggest that three-layer
      two-step PR using peritoneum during RARP is a simple and feasible method seeming
      to improve early recovery of postoperative continence compared with standard two
      step PR, although larger multicenter randomized controlled trials will be needed.

PMID- 29061069
TI  - Effects of Ferroportin-Mediated Iron Depletion in Cells Representative of
      Different Histological Subtypes of Prostate Cancer.
AB  - AIMS: Ferroportin (FPN) is an iron exporter that plays an important role in
      cellular and systemic iron metabolism. Our previous work has demonstrated that
      FPN is decreased in prostate tumors. We sought to identify the molecular pathways
      regulated by FPN in prostate cancer cells. RESULTS: We show that overexpression
      of FPN induces profound effects in cells representative of multiple histological
      subtypes of prostate cancer by activating different but converging pathways.
      Induction of FPN induces autophagy and activates the transcription factors tumor
      protein 53 (p53) and Kruppel-like factor 6 (KLF6) and their common downstream
      target, cyclin-dependent kinase inhibitor 1A (p21). FPN also induces cell cycle
      arrest and stress-induced DNA-damage genes. Effects of FPN are attributable to
      its effects on intracellular iron and can be reproduced with iron chelators.
      Importantly, expression of FPN not only inhibits proliferation of all prostate
      cancer cells studied but also reduces growth of tumors derived from castrate
      resistant adenocarcinoma C4-2 cells in vivo. INNOVATION: We use a novel model of
      FPN expression to interrogate molecular pathways triggered by iron depletion in
      prostate cancer cells. Since prostate cancer encompasses different subtypes with
      a highly variable clinical course, we further explore how histopathological
      subtype influences the response to iron depletion. We demonstrate that prostate
      cancer cells that derive from different histopathological subtypes activate
      converging pathways in response to FPN-mediated iron depletion. Activation of
      these pathways is sufficient to significantly reduce the growth of treatment
      refractory C4-2 prostate tumors in vivo. CONCLUSIONS: Our results may explain why
      FPN is dramatically suppressed in cancer cells, and they suggest that FPN
      agonists may be beneficial in the treatment of prostate cancer. Antioxid. Redox
      Signal. 00, 000-000.

PMID- 29061070
TI  - Ureteroscopic Laser Lithotripsy: A Review of Dusting vs Fragmentation with
      Extraction.
AB  - INTRODUCTION: Ureteroscopic laser lithotripsy is becoming the most commonly
      utilized treatment for patients with urinary calculi. The Holmium:YAG (yttrium
      aluminum garnet) laser is integral to the operation and is the preferred flexible
      intracorporeal lithotrite. In recent years, there has been increasing interest in
      examining the effect of varying the laser settings on the effectiveness of stone
      treatment. Herein, we review the two primary laser treatment approaches: dusting
      and fragmentation with extraction. METHODS: We reviewed PubMed and MEDLINE
      databases from January 1976 through January 2017. All authors participated in the
      development of consensus definitions of dusting and fragmentation with
      extraction. The review protocol adhered to preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) methodology. RESULTS: When the
      Holmium:YAG laser is used to treat stones, there are two parameters that can be
      adjusted: power (J) and frequency (Hz). In one treatment paradigm, which became
      termed "fragmentation with extraction," laser settings that relied on high energy
      and low frequency were used. Another paradigm, which became termed "dusting,"
      utilized low energy and high frequency settings, which had the effect of breaking
      off exceedingly small fragments from the stone. CONCLUSIONS: Both dusting and
      fragmentation with extraction approaches to ureteroscopic stone treatment are
      effective. In fact, there is little evidence that one approach is better than the
      other. However, each does have relative advantages and disadvantages, which
      should be considered. Although dusting tends to be associated with shorter
      procedure times and a lower risk of ureteral damage, this approach may place the
      patient at increased risk for future stone events should all of the resultant
      debris not be expelled from the collecting system. The active removal associated
      with fragmentation with extraction, in contrast, may provide for a more complete
      initial stone clearance.

PMID- 29061071
TI  - Does Metformin Modulate Endoplasmic Reticulum Stress and Autophagy in Type 2
      Diabetic Peripheral Blood Mononuclear Cells?
AB  - Since type 2 diabetes (T2D) is associated with oxidative stress and metformin has
      been shown to exert a protective role against the said stress, we wondered
      whether metformin treatment might also modulate endoplasmic reticulum (ER) stress
      and autophagy in leukocytes of T2D patients. We studied 53 T2D patients (37 of
      whom had been treated with metformin 1700 mg for at least 1 year) and 30 healthy
      volunteers. Leukocytes from both groups of T2D patients exhibited increased
      protein levels of 78-kDa glucose-regulated protein (GRP78) with respect to
      controls, whereas activating transcription factor 6 (ATF6) was enhanced
      specifically in nonmetformin-treated T2D, and (s-xbp1) and phosphorylated
      eukaryotic initiation factor 2alpha (p-eIF2alpha) increased only in the metformin
      treated group. The autophagy markers beclin1 (becn1), autophagy-related 7 (atg7),
      and microtubule-associated protein 1A/1B-light chain 3II/I (LC3 II/I) increased
      in nonmetformin-treated T2D, and metformin treatment reduced mitochondrial
      superoxide and increased glutathione (GSH) levels. Our observations raise the
      question of whether metformin treatment could reduce oxidative stress and act as
      an ER stress modulator in T2D patients by promoting an adaptive unfolded protein
      response (s-xbp1 and p-eIF2alpha) in their leukocytes; this was in contrast with
      nonmetformin-treated patients whose response could be driven by the ATF6
      dependent pro-apoptotic pathway. Further, our findings lead to us to form the
      hypothesis of an autophagy-dependent clearance of misfolded proteins in
      nonmetformin-treated T2D patients that could be repressed by metformin treatment.
      Antioxid. Redox Signal. 28, 1562-1569.

PMID- 29061072
TI  - Perinatally HIV-Infected Youths After Transition from Pediatric to Adult Care, a
      Single-Center Experience from Northern Italy.
AB  - With the development of combination antiretroviral therapy (cART), the first
      generation of perinatally HIV-infected children has reached young adulthood. A
      retrospective study was conducted on perinatally HIV-infected young adults after
      transition to adult care in Brescia (Northern Italy). Twenty-four patients were
      transferred to Infectious Disease outpatient Clinic from Pediatric Clinic between
      2004 and 2016. Median age at transition was 18 years. 37.5% were male, and 75%
      were Italian. Median CD4+ T-cell count was 534 cell/MUL, and 9/24 presented
      detectable HIV-RNA at the time of transition. At month 12 after transition,
      median CD4+ T-cell count was 626 cell/MUL, and HIV-RNA was still detectable in
      25% of patients. Nineteen patients were still in care at the end of follow-up
      (median of 52 months); 100% on cART, with undetectable HIV-RNA and a median CD4+
      T-cell count of 716 cell/MUL. After transition, cART regimen was modified in
      14/19 patients (in 13 of them it was modified at least twice). Resistance testing
      is available for 13 patients showing resistance-associated mutations to at least
      one class of drugs in 9 patients. Transition to adult care is a critical point
      and youths present lower rates of viral suppression compared to adults. We
      observed 80% of viral suppression (5 young patients were lost to follow-up and
      considered as failures), notwithstanding social problems and resistance
      mutations. With the availability of more potent and better-tolerated drugs,
      optimization of cART is possible also in this previously difficult-to-treat group
      of patients. Novel tools to address adherence to cART in young adults and
      teenagers will also be needed.

PMID- 29061073
TI  - The transition from youth to adult mental health services and the economic impact
      on youth and their families.
AB  - The transition from Child and Adolescent Mental Health Services (CAMHS) to Adult
      Mental Health Services (AMHS) can be challenging for youth, their families, and
      healthcare providers. The purpose of this study was to identify, summarize, and
      assess evidence found in scholarly literature regarding the economic impact on
      youth and their families during the transition from CAMHS to AMHS. Relevant
      studies were identified through a search of 7 electronic platforms. The search
      identified 829 articles; 5 of which met all inclusion criteria. Evidence from the
      included studies suggests that, when continuity of care is lacking, transitions
      from CAMHS to AMHS have substantial impacts on the financial demands of youth and
      their families. These demands are due to increases in the cost of care, loss of
      employment income and productivity, and changes in insurance coverage. However,
      there remains limited information in this area, which highlights the need for
      further research.

PMID- 29061074
TI  - Design of effective interventions for smoking cessation through financial and non
      financial incentives.
AB  - Smoking has a tremendous negative impact on the Canadian economy and contributes
      to growing costs in the healthcare system. Efforts to reduce smoking rates may
      therefore reduce strain on the healthcare system and free up scarce resources.
      Academic literature on economic smoking cessation incentives presents a countless
      variety of interventions that have met with varying degrees of success. This
      study reviews six different variables used in the design of incentives in smoking
      cessation interventions: direction, form, magnitude, certainty, recipient
      grouping, and target demographic. The purpose of this study is to provide
      analysis and recommendations about the contribution of each variable into the
      overall effectiveness of smoking cessation programs and help health leaders
      design better interventions according to their specific needs.

PMID- 29061075
TI  - Ethical issues in health philanthropy.
AB  - Health leaders in Canada face a myriad of challenges with healthcare philanthropy
      not just the practical question of how to be successful but also ethical
      questions. Is fundraising in partnership with companies that are implicated in
      the so-called lifestyle diseases appropriate? When does appropriate recognition
      for donors or volunteers cross the line into facilitating preferential access to
      care? Ethical decision-making in health philanthropy considers appropriate
      recognition or partnership in donor relations in the context of the public good
      with which healthcare institutions are entrusted and the fiduciary
      responsibilities of hospitals and clinicians to patients.

PMID- 29061076
TI  - Genetic non-discrimination policy in Canada: Assessing windows of opportunity for
      policy change.
AB  - As the ease of obtaining genetic information for both the diagnosis and treatment
      of diseases has become increasingly common, so have concerns about the misuse of
      such information. The obstacles Canada faces in adopting genetic non
      discrimination legislation have left health leaders with a lack of clear
      direction. Using the Kingdon agenda-setting framework, this article will identify
      lost opportunities for policy change and will analyze the potential for the
      adoption of a genetic non-discrimination policy in Canada. Windows of opportunity
      for policy change have existed in the past, but these windows have closed prior
      to a policy being adopted. More recently, the alignment of problem, policy, and
      politics streams in the agenda-setting process has resulted in a new window of
      opportunity. The adoption of a clear and coherent policy will provide the public
      with protection and health leaders with greater direction around genetic
      information.

PMID- 29061077
TI  - Value agenda for heart failure in Ontario: Application of the Porter model.
AB  - Value in healthcare is a challenge that is faced all over the world; costs
      continue to rise despite efforts to increase quality and efficient healthcare
      delivery. Heart failure is a progressive chronic condition that has been
      demonstrated to benefit from close monitoring with positive effects on mortality
      and morbidity when well managed. This article will review the Porter model for
      value in healthcare by comparing the current state of heart failure management in
      Ontario, Canada, with the six key concepts of the value agenda. The Ontario
      quality-based procedure model has been implemented for heart failure management
      and will be applied against the Porter model to provide an increased
      understanding of how managers can think differently about patient outcomes. An
      examination as to how the quality and value of the treatment of this condition
      can be improved will be conducted using the principles of the value agenda.

PMID- 29061078
TI  - Introducing personalized health for the family: the experience of a single
      hospital system.
AB  - Pharmacogenetic testing is leading the personalized health movement, gradually
      being implemented in a variety of healthcare settings. To inform the efforts of
      other hospital and clinical practices implementing personalized health or
      medicine applications, we describe the implementation of a newborn
      pharmacogenetic testing program at Inova Health System (VA, USA). In particular,
      we describe the efforts to gather patient feedback through focus groups, the
      training and program staff, the pilot program and our experiences to date. In our
      experience, a multidisciplinary team was essential to address the myriad facets
      of program development and implementation as well as an in-person approach to
      introduce testing and patient education.

PMID- 29061079
TI  - Precision oncology: neither a silver bullet nor a dream.
AB  - Precision oncology is not an illusion, nor is it the magic bullet that will
      eradicate all cancers. Precision oncology is simply another weapon in our growing
      armament against cancer. Rather than honing in on the failures of a relatively
      young field, one should advocate for integrating its successes into widespread
      clinical practice, especially for indications, such as: ABL, ALK, BRAF, BRCA1,
      BRCA2, EGFR, KIT, KRAS, PDGFRA, PDGFRB, ROS1, BCR-ABL, FLT3 and ROS1, where
      aberrations have been shown to alter responses to US FDA approved drugs - that
      is, level 1 data. Moreover, to truly assess the promise of precision oncology, we
      must first begin by defining our expectations for this field. Importantly, we
      must recognize that the conception of precision oncology arose as an antithesis
      of the 'one-size fits all' cancer therapeutics approach. Consequently, tools used
      for evaluating these conventional, large-scale trials, are not directly
      transferable for assessing nonconventional, smaller-scale trials needed for
      evaluating precision oncology. Hence, a thorough vetting of precision oncology as
      another tool of the trade, must first begin by reassessing our expectations for
      this field, as well as current clinical trial designs and end point measurements.
      Importantly, we must recognize that most targeted therapy approaches are in their
      infancy, with only monotherapy approaches being assessed and combination
      therapies likely being necessary to fulfill the promise of precision oncology.

PMID- 29061080
TI  - Integration of Community Pharmacists in Transition of Care (TOC) Services:
      Current Trends and Pharmacist Perceptions.
AB  - BACKGROUND: Barriers exist for patients transitioning from one health-care
      setting to another, or to home, and health-care systems are falling short of
      meeting patient needs during this time. Community pharmacist incorporation poses
      a solution to the current communication breakdown and high rates of medication
      errors during transitions of care (TOC). The purpose of this study was to
      determine community pharmacists' involvement in and perceptions of TOC services.
      METHODS: Cross-sectional study using electronic surveys nationwide to pharmacists
      employed by a community pharmacy chain. RESULTS: Of 7236 pharmacists surveyed,
      546 (7.5%) responded. Only 33 (6%) pharmacists reported their pharmacy
      participates in TOC services. Most pharmacists (81.5%) reported receiving
      discharge medication lists. The most common reported barrier to TOC participation
      is lack of electronic integration with surrounding hospitals (51.1%). Most
      pharmacists agreed that (1) it is valuable to receive discharge medication lists
      (83.3%), (2) receiving discharge medication lists is beneficial for patients'
      health (89.1%), (3) discharge medication list receipt improves medication safety
      (88.8%). CONCLUSIONS: Most pharmacists reported receiving discharge medication
      lists and reported discharge medication lists are beneficial, but less than half
      purposefully used medication lists. To close TOC gaps, health-care providers must
      collaborate to overcome barriers for successful TOC services.

PMID- 29061081
TI  - Pharmacogenetics of trazodone in healthy volunteers: association with
      pharmacokinetics, pharmacodynamics and safety.
AB  - AIM: The aim was to evaluate the effect of polymorphisms in metabolizing enzymes
      and transporters on the pharmacokinetics, pharmacodynamics and adverse effects of
      trazodone in healthy volunteers. MATERIALS & METHODS: 36 healthy volunteers
      receiving a single 100-mg oral dose of trazodone were genotyped for 11 variants
      in CYP3A4, CYP3A5, CYP2D6 and ABCB1 by real-time PCR. Plasma concentrations were
      measured using liquid chromatography-tandem mass spectrometry method. RESULTS &
      CONCLUSION: Sex affected the pharmacokinetics of trazodone with higher clearance
      in women. Polymorphisms in ABCB1, but not in CYP3A or CYP2D6, influenced
      trazodone pharmacokinetics. Trazodone decreased blood pressure and prolonged the
      corrected QT interval interval. CYP2D6 and ABCB1 polymorphisms were associated
      with the incidence of dizziness and prolonged corrected QT interval,
      respectively. Subjects with adverse drug reactions had lower concentrations of
      trazodone suggesting its metabolite (m-chlorophenylpiperazine) could be
      responsible for these effects.

PMID- 29061082
TI  - Motor planning in children with cerebral palsy: A longitudinal perspective.
AB  - INTRODUCTION: Motor planning is important for daily functioning. Deficits in
      motor planning can result in slow, inefficient, and clumsy motor behavior and are
      linked to disruptions in performance of activities of daily living in children
      with cerebral palsy (CP). However, the evidence in CP is primarily based on cross
      sectional data. METHOD: Data are presented on the development of motor planning
      in children with CP using a longitudinal design with three measurement occasions,
      each separated by 1 year. Twenty-two children with CP (9 boys, 13 girls; age in
      years;months, M = 7;1, SD = 1;2) and 22 age-matched controls (10 boys, 12 girls,
      M  = 7;1, SD = 1;3) participated. Children performed a bar transport task in
      which some conditions ("critical angles") required participants to sacrifice
      initial posture comfort in order to achieve end-state comfort. Performance on
      critical trials was analyzed using linear growth curve modeling. RESULTS: In
      general, children with CP showed poor end-state planning for critical angles.
      Importantly, unlike in controls, motor planning ability did not improve across
      the three measurement occasions in children with CP. CONCLUSION: These
      longitudinal results show that motor planning issues in CP do not resolve with
      development over childhood. Strategies to enhance motor planning are suggested
      for intervention.

PMID- 29061083
TI  - Immuno-Oncology-The Translational Runway for Gene Therapy: Gene Therapeutics to
      Address Multiple Immune Targets.
AB  - Cancer therapy is once again experiencing a paradigm shift. This shift is based
      on extensive clinical experience demonstrating that cancer cannot be successfully
      fought by addressing only single targets or pathways. Even the combination of
      several neo-antigens in cancer vaccines is not sufficient for successful, lasting
      tumor eradication. The focus has therefore shifted to the immune system's role in
      cancer and the striking abilities of cancer cells to manipulate and/or deactivate
      the immune system. Researchers and pharma companies have started to target the
      processes and cells known to support immune surveillance and the elimination of
      tumor cells. Immune processes, however, require novel concepts beyond the
      traditional "single-target-single drug" paradigm and need parallel targeting of
      diverse cells and mechanisms. This review gives a perspective on the role of gene
      therapy technologies in the evolving immuno-oncology space and identifies gene
      therapy as a major driver in the development and regulation of effective cancer
      immunotherapy. Present challenges and breakthroughs ranging from chimeric antigen
      receptor T-cell therapy, gene-modified oncolytic viruses, combination cancer
      vaccines, to RNA therapeutics are spotlighted. Gene therapy is recognized as the
      most prominent technology enabling effective immuno-oncology strategies.

PMID- 29061085
TI  - Do genes affect morphine response?

PMID- 29061084
TI  - The improvement in respiratory function by inspiratory muscle training is due to
      structural muscle changes in patients with stroke: a randomized controlled pilot
      trial.
AB  - BACKGROUND: The changes effected by the inspiratory muscle training (IMT) on the
      structure of inspiratory muscles such as on the diaphragm, in patients with
      stroke, is unclear. OBJECTIVE: To investigate the effect of IMT on inspiratory
      function, diaphragm thickness, walking endurance, and fatigue in patients with
      stroke. METHODS: A total of 30 patients with stroke were randomized to either the
      experimental group or the control group. The experimental group (n = 15)
      underwent inspiratory muscle training with resistance adjusted to 30% of maximal
      inspiratory pressure, 90 breaths a day, 5 times a week for 6 weeks. Both groups
      received regular physical therapy for the same amount of time. The primary
      outcome measure was the diaphragm thickness ratio. The secondary outcomes were
      inspiratory function; maximal inspiratory pressure and inspiratory muscle
      endurance; and gait endurance and fatigue. RESULTS: There were significant
      differences between the two groups in the thickness ratio on the affected
      diaphragm thickness (medium effect size), maximal inspiratory pressure (medium
      effect size), and inspiratory muscle endurance (large effect size; Bonferroni
      correction p < 0.005). The gait endurance (medium effect size) and fatigue (small
      effect size) showed no significant differences in the between group comparison.
      CONCLUSION: Inspiratory muscle training was effective in improving respiratory
      function and inducing structural changes, especially in the affected diaphragm.

PMID- 29061086
TI  - Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai
      HIV-infected patients.
AB  - AIM: To develop a population pharmacokinetic model and identify sources of
      variability, genetic and nongenetic factors, of tenofovir. METHODS: The ABCC2 and
      ABCC4 polymorphisms were genotyped in 342 patients. A nonlinear mixed effects
      model was used to develop the population pharmacokinetic model and investigate
      the influence of these polymorphisms and other patient specific covariates on the
      pharmacokinetics of tenofovir. RESULTS: The estimated glomerular filtration rate
      calculated by the Cockcroft and Gault equation, concomitant use of
      lopinavir/ritonavir and ABCC4 3463A>G polymorphism were associated with tenofovir
      apparent oral clearance (CL/F). The use of lopinavir/ritonavir decreased
      tenofovir CL/F by 25%. Patients carrying ABCC4 3463 AG or GG had a tenofovir CL/F
      11% higher than those with genotype AA. CONCLUSION: Renal function, co-medication
      and genetic variation impact the pharmacokinetics of tenofovir. These factors
      should be taken into consideration to guide the individual tenofovir disoproxil
      fumarate dosage regimen in Thai HIV-infected patients.

PMID- 29061087
TI  - OCT1 pharmacogenetics in pain management: is a clinical application within reach?
AB  - Beside drug metabolizing enzymes alsogenetically variable membrane transporters
      may substantially contribute to the interindividual variability in
      pharmacokinetics and efficacy of opioids and other analgesics. The organic cation
      transporter OCT1 is strongly expressed in the sinusoidal membrane of the human
      liver. It may affect hepatic uptake and thus limit metabolic rates. OCT1 is
      highly genetically variable. Genetic polymorphisms lead to substantially reduced
      OCT1 activity in up to 9% of the Europeans and the white Americans. This review
      summarize the data on the effect of OCT1 polymorphisms on pharmacokinetics and
      efficacy of opioids like morphine, codeine, and tramadol and of anti-migraine
      drugs. It discuss currently possible applications and perspectives for
      establishing OCT1 pharmacogenetics as a useful tool in personalized pain
      management.

PMID- 29061088
TI  - Workplace bullying and relationships with health and performance among a sample
      of New Zealand veterinarians.
AB  - AIM: To examine the relationships between workplace bullying, destructive
      leadership and team conflict, and physical health, strain, self-reported
      performance and intentions to quit among veterinarians in New Zealand, and how
      these relationships could be moderated by psychological capital and perceived
      organisational support. METHODS: Data were collected by means of an online
      survey, distributed to members of the New Zealand Veterinary Association.
      Participation was voluntary and all responses were anonymous and confidential.
      Scores for the variables measured were based on responses to questions or
      statements with responses categorised on a linear scale. A series of regression
      analyses were used to assess mediation or moderation by intermediate variables on
      the relationships between predictor variables and dependent variables. RESULTS:
      Completed surveys were provided by 197 veterinarians, of which 32 (16.2%) had
      been bullied at work, i.e. they had experienced two or more negative acts at
      least weekly over the previous 6 months, and nine (4.6%) had experienced cyber
      bullying. Mean scores for workplace bullying were higher for female than male
      respondents, and for non-managers than managers (p<0.01). Scores for workplace
      bullying were positively associated with scores for destructive leadership and
      team conflict, physical health, strain, and intentions to quit (p<0.001).
      Workplace bullying and team conflict mediated the relationship between
      destructive leadership and strain, physical health and intentions to quit.
      Perceived organisational support moderated the effects of workplace bullying on
      strain and self-reported job performance (p<0.05). CONCLUSIONS: Relatively high
      rates of negative behaviour were reported by veterinarians in this study, with
      16% of participants meeting an established criterion for having been bullied. The
      negative effects of destructive leadership on strain, physical health and
      intentions to quit were mediated by team conflict and workplace bullying. It
      should be noted that the findings of this study were based on a survey of self
      selected participants and the findings may not represent the wider population of
      New Zealand veterinarians.

PMID- 29061090
TI  - Neurodegenerative Dementias After Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is often considered to be a risk factor for the
      later development of neurodegenerative conditions, but some findings do not
      support a link. Differences in research methods, clinical samples, and
      limitations encountered when assessing and documenting TBI details likely
      contribute to the mixed reports in the literature. Despite some variability in
      findings, a review of the literature does provide support for the notion that TBI
      appears to be associated with earlier onset of some neurodegenerative disorders,
      although clearly not everyone with a TBI appears to be at an increased risk.
      Whereas a mechanistic link remains unknown, TBI has been found to initiate an
      accumulation of pathological processes related to several neurodegenerative
      disorders. The authors propose a hypothetical model that relates TBI to the
      development of pathological burden overlapping with some neurodegenerative
      conditions, in which onset of cognitive/behavioral impairments is hastened in
      some individuals, but pathological processes stabilize afterward, resulting in a
      similar course of decline to individuals with dementia who do not have a history
      of TBI.

PMID- 29061089
TI  - Dyslexic Characteristics of Chinese-Speaking Semantic Variant of Primary
      Progressive Aphasia.
AB  - Reading disorder is a recognized feature in primary progressive aphasia (PPA).
      Surface dyslexia, characterized by regularization errors, is typically seen in
      the English-speaking semantic variant of PPA (svPPA). However, dyslexic
      characteristics of other languages, particularly logographical languages such as
      Chinese, remain sparse in the literature. This study aims to characterize and
      describe the dyslexic pattern in this group of patients by comparing an English
      speaking svPPA group with a Chinese-speaking svPPA group. The authors
      hypothesized that Chinese-speaking individuals with svPPA would likely commit
      fewer surface dyslexic errors. By accessing the database of Singapore's National
      Neuroscience Institute and the National Alzheimer's Coordinating Center of the
      United States, the authors identified three Chinese-speaking and 18 English
      speaking patients with svPPA, respectively, for comparison. The results suggest
      that, instead of surface dyslexia, svPPA in Chinese-speaking individuals is
      characterized by a profound deep dyslexic error. Based on current evidence
      suggesting the role of the temporal pole as a semantic convergence center, the
      authors conclude that this region also mediates and converges lexical-semantic
      significance in logographical languages.

PMID- 29061091
TI  - Exploring the Spectrum of Subcortical Hyperintensities and Cognitive Decline.
AB  - White matter hyperintensities (WMHs) include periventricular WMH (pvWMH) and deep
      WMH. When hyperintensities in the basal ganglia or brainstem are included, the
      collective term is subcortical hyperintensities. Both WMH and medial temporal
      lobe atrophy (MTA) are risk factors for cognitive decline. This prospective study
      enrolled participants aged 50-85 years and followed their neuropsychological
      assessments annually for 2 years to explore the interactive effects of WMH and
      MTA on longitudinal clinical decline. Brain MRI was performed at the beginning of
      enrollment. Of the 200 participants, 57 were "normal" individuals, 40 had
      dysexecutive mild cognitive impairment, 53 had amnestic mild cognitive
      impairment, and 50 had Alzheimer's disease (AD). Overall, MTA significantly
      correlated with pvWMH (p=0.0004) but not with deep WMH, as defined by criteria
      using the Scheltens' Scale. Total Scheltens' score was specifically associated
      with the domain of semantic fluency (beta=-0.4, 95% CI=-0.7 to -0.2, p=0.002),
      which remained significant when adjusting for MTA (beta=-0.3, 95% CI=-0.5 to 
      0.1, p=0.017). The pvWMH was significantly higher in AD subjects than in normal
      control subjects (beta=0.3, 95% CI=0.1 to 0.4, p=0.001), especially the
      periventricular occipital caps (beta=0.2, 95% CI=0.1 to 0.3, p=0.0003). Cox
      proportional hazards model showed that the periventricular bands (PVB) predicted
      1-year clinical decline (hazard ratio [HR]=5.3, 95% CI=1.8 to 15.7, p=0.002),
      which remained significant when further adjusting for MTA (HR=4.0, 95% CI=1.3 to
      12.1, p=0.013). In summary, pvWMH, especially the occipital caps, was correlated
      with MTA and the AD subgroup. Assessment of semantic fluency may be useful for
      the clinical evaluation of the degree of subcortical hyperintensity burden.
      Visual rating of PVB could be an independent predictor for 1-year clinical
      decline.

PMID- 29061092
TI  - Facilitators and constraints at each stage of the migration decision process.
AB  - Behavioural models of migration emphasize the importance of migration decision
      making for the explanation of subsequent behaviour. But empirical migration
      research regularly finds considerable gaps between those who intend to migrate
      and those who actually realize their intention. This paper applies the Theory of
      Planned Behaviour, enriched by the Rubicon model, to test specific hypotheses
      about distinct effects of facilitators and constraints on specific stages of
      migration decision-making and behaviour. The data come from a tailor-made panel
      survey based on random samples of people drawn from two German cities in 2006-07.
      The results show that in conventional models the effects of facilitators and
      constraints on migration decision-making are likely to be underestimated.
      Splitting the process of migration decision-making into a pre-decisional and a
      pre-actional phase helps to avoid bias in the estimated effects of facilitators
      and constraints on both migration decision-making and migration behaviour.

PMID- 29061093
TI  - Multistate modelling extended by behavioural rules: An application to migration.
AB  - We propose to extend demographic multistate models by adding a behavioural
      element: behavioural rules explain intentions and thus transitions. Our framework
      is inspired by the Theory of Planned Behaviour. We exemplify our approach with a
      model of migration from Senegal to France. Model parameters are determined using
      empirical data where available. Parameters for which no empirical correspondence
      exists are determined by calibration. Age- and period-specific migration rates
      are used for model validation. Our approach adds to the toolkit of demographic
      projection by allowing for shocks and social influence, which alter behaviour in
      non-linear ways, while sticking to the general framework of multistate modelling.
      Our simulations yield that higher income growth in Senegal leads to higher
      emigration rates in the medium term, while a decrease in fertility yields lower
      emigration rates.

PMID- 29061094
TI  - Modelling and simulating decision processes of linked lives: An approach based on
      concurrent processes and stochastic race.
AB  - Individuals' decision processes play a central role in understanding modern
      migration phenomena and other demographic processes. Their integration into agent
      based computational demography depends largely on suitable support by a modelling
      language. We are developing the Modelling Language for Linked Lives (ML3) to
      describe the diverse decision processes of linked lives succinctly in continuous
      time. The context of individuals is modelled by networks the individual is part
      of, such as family ties and other social networks. Central concepts, such as
      behaviour conditional on agent attributes, age-dependent behaviour, and
      stochastic waiting times, are tightly integrated in the language. Thereby,
      alternative decisions are modelled by concurrent processes that compete by
      stochastic race. Using a migration model, we demonstrate how this allows for
      compact description of complex decisions, here based on the Theory of Planned
      Behaviour. We describe the challenges for the simulation algorithm posed by
      stochastic race between multiple concurrent complex decisions.

PMID- 29061095
TI  - Choosing the choice: Reflections on modelling decisions and behaviour in
      demographic agent-based models.
AB  - This paper investigates the issues associated with choosing appropriate models of
      choice for demographic agent-based models. In particular, we discuss the
      importance of context, time preference, and dealing with uncertainty in decision
      modelling, as well as the heterogeneity between agents in their decision-making
      strategies. The paper concludes by advocating empirically driven, modular, and
      multi-model approaches to designing simulations of human decision-making, given
      the lack of an agreed strategy for dealing with any of these issues. Furthermore,
      we suggest that an iterative process of data collection and simulation
      experiments, with the latter informing future empirical data collection, should
      form the basis of such an endeavour. The discussion is illustrated with reference
      to selected demographic agent-based models, with a focus on migration.

PMID- 29061096
TI  - The science of choice: an introduction.

PMID- 29061097
TI  - The reversal of the gender gap in education and relative divorce risks: A matter
      of alternatives in partner choice?
AB  - Recent evidence from the United States suggests that the reversal of the gender
      gap in education was associated with changes in relative divorce risks:
      hypogamous marriages, where the wife was more educated than the husband, used to
      have a higher divorce risk than hypergamous marriages, where the husband was more
      educated, but this difference has disappeared. One interpretation holds that this
      may result from cultural change, involving increasing social acceptance of
      hypogamy. We propose an alternative mechanism that need not presuppose cultural
      change: the gender-gap reversal in education has changed the availability of
      alternatives from which highly educated women and men can choose new partners.
      This may have lowered the likelihood of women leaving husbands with less
      education and encouraged men to leave less educated spouses. We applied an agent
      based model to twelve European national marriage markets to illustrate that this
      could be sufficient to create a convergence in divorce risks.

PMID- 29061099
TI  - An industry update: the latest news in therapeutic delivery.
AB  - The present industry update covers the period 1-31 July 2017. Information was
      sourced primarily from company press releases, regulatory and patent agencies,
      scientific literature and various news websites. There was positive approval news
      this month for GlaxoSmithKline for its new self-injecting treatment for systemic
      lupus erythematosus but less positive news for Ocular Therapeutix, a new drug
      application for its treatment for postoperative ocular pain, DEXTENZATM was
      rejected for a second time. Endo Pharmaceuticals agreed to withdraw its opioid
      formulation Opana(r)Er due to abuse concerns. Collaborations for novel
      therapeutic delivery research were announced this month by Takeda and
      BioSurfaces, Catelent and Rutgers University, Lilly and Purdue University and
      Titan Pharmaceuticals with Walter Reed and the Southwest Research Institute. A
      number of companies announced significant financing deals to allow for the
      clinical development of products with enhanced delivery options including Sebacia
      and Diasome.

PMID- 29061100
TI  - A complete world of design adaptation and product specificities for injectable
      drug delivery.

PMID- 29061098
TI  - The Cognitive Reserve Model in the Development of Delirium: The Successful Aging
      After Elective Surgery Study.
AB  - We evaluated the role of cognitive and brain reserve markers in modifying the
      risk of postoperative delirium associated with a pathophysiologic marker. The
      Successful Aging after Elective Surgery study (SAGES) enrolled 556 adults age
      >=70 years without dementia scheduled for major surgery. Patients were assessed
      preoperatively and daily during hospitalization for delirium. We used C-reactive
      protein (CRP) as a pathophysiologic marker of inflammation, previously associated
      with delirium. Markers of reserve included vocabulary knowledge, education,
      cognitive activities, occupation type and complexity, head circumference,
      intracranial volume, and leisure activities. Vocabulary knowledge, cognitive
      activities, and education significantly modified the association of CRP and
      postoperative delirium ( P < .01). However, effect sizes-when statistically
      significant-were small in magnitude. The strongest effect modification was
      observed for vocabulary knowledge: high scores were generally protective but not
      at high levels of CRP. Select reserve markers attenuate the risk of delirium
      associated with lower grade inflammatory processes, supporting the role of
      reserve in delirium.

PMID- 29061101
TI  - Nanomedicine for cancer diagnosis and therapy: advancement, success and structure
      activity relationship.
AB  - Multifunctional nanoparticles (NPs), composed of organic and inorganic materials,
      have been explored as promising drug-delivery vehicles for cancer diagnosis and
      therapy. The success of nanosystems has been attributed to its smaller size,
      biocompatibility, selective tumor accumulation and reduced toxicity. The
      relationship among numbers of molecules in payload, NP diameter and encapsulation
      efficacy have crucial role in clinical translation. Advancement of
      bioengineering, and systematic fine-tuning of functional components to NPs have
      diversified their optical and theranostic properties. In this review, we
      summarize wide varieties of NPs, such as ultrasmall polymer-lipid hybrid NPs,
      dendrimers, liposomes, quantum dots, carbon nanotubes, gold NPs and iron oxide
      NPs. We also discuss their tumor targetability, tissue penetration,
      pharmacokinetics, and therapeutic and diagnostic properties. [Formula: see text].

PMID- 29061102
TI  - Delivering natural products and biotherapeutics to improve drug efficacy.
AB  - Due to the increasing problem of drug resistance, new and improved medicines are
      required. Natural products and biotherapeutics offer a vast resource for new
      drugs; however, challenges, including the cost and time taken for traditional
      drug discovery processes and the subsequent lack of investment from the
      pharmaceutical industry, are associated with these areas. New techniques are
      producing compounds with appropriate activity at a faster rate. While the
      formulation of these combined with drug-delivery systems offers a promising
      approach for expanding the drug developments available to modern medicine. Here,
      various classes of drug-delivery systems are described and the advantages they
      bring to small molecule and biotherapeutic targeting are highlighted. This is an
      attractive approach to the pharmaceutical industry and the rising trend in
      research in this area is examined in brief. [Formula: see text].

PMID- 29061103
TI  - Integration of nano drug-delivery system with cancer immunotherapy.
AB  - Immune checkpoint therapy represents a new, revolutionary type of cancer therapy,
      but emerging evidence indicates that only a minority of patients will benefit
      from it. The issue of how to improve and widen the clinical response is a pivotal
      issue, and combining other types of therapy with immune checkpoint inhibitors is
      currently under development. A nanotechnology-based drug-delivery system (nano
      DDS) could be an important contribution to the development of an effective
      combination therapy. In this document, we review recent findings in the field of
      tumor immunology, which provide a strategy for an efficient combination therapy,
      and discuss nano DDS that are associated with cancer immunotherapy and nano DDS
      strategies based on the immune status in tumor microenvironments.

PMID- 29061105
TI  - Water-soluble polyacetylene: a promising tool for sustainable drug delivery?

PMID- 29061104
TI  - FDM 3D printing of modified drug-delivery systems using hot melt extrusion: a new
      approach for individualized therapy.
AB  - The production process of 3D-printed drugs offers unique advantages such as the
      possibility of individualizing the drug therapy and easily associating different
      drugs and release technologies in the same pharmaceutical unit. Fused deposition
      modeling, a 3D printing technique, seems especially interesting for
      pharmaceutical applications, due to its low cost, precise and reproducible
      control of the printed structures, and versatility for industrial and laboratory
      scale. This technique combined with another technology already adapted for the
      pharmaceutical industry, the hot melt extrusion, is able to incorporate various
      mechanisms of modified drug release. This special report aims to bring together
      data of the experimental progress achieved using the fused deposition modeling 3D
      printing combined with hot melt extrusion technique and its potential in drug
      delivery. [Formula: see text].

PMID- 29061106
TI  - Potential enhancement and targeting strategies of polymeric and lipid-based
      nanocarriers in dermal drug delivery.
AB  - Nanocarriers used for alternative drug-delivery strategies have gained interest
      due to improved penetration and delivery of drugs into specific regions of the
      skin in recent years. Dermal drug delivery via polymeric-based nanocarriers
      (polymeric nanoparticles, micelles, dendrimers) and lipid-based nanocarriers
      (solid-lipid nanoparticles and nanostructured lipid carriers, vesicular
      nanocarriers including liposomes, niosomes, transfersomes and ethosomes) has been
      widely investigated. Although penetration of nanocarriers through the intact skin
      could be restricted, these carriers are particularly considered as feasible for
      the treatment of dermatological diseases in which the skin barrier is disrupted
      and also for follicular delivery of drugs for management of skin disorders such
      as acne. This review mainly highlights the recent approaches on potential
      penetration enhancement and targeting mechanisms of these nanocarriers.

PMID- 29061107
TI  - Non-endoscopic minimally invasive evacuation of intracerebral hematoma (ICH): A
      case report.
AB  - Spontaneous intracerebral hemorrhage (ICH) is one of the most serious causes of
      stroke, leading to high rates of disability and mortality. In addition to
      intensive medical treatment, surgery may help to improve the prognosis in
      patients with ICH. A rapid reversal of coagulopathy is essential in these
      patients, although it may be difficult to achieve in various bleeding disorders.
      In such cases, when surgery is needed, a minimally invasive approach is
      recommended. In this case report, we described and shortly discussed the
      evacuation of ICH with a minimally invasive non-endoscopic surgical technique.

PMID- 29061109
TI  - dCATCH-Seq: improved sequencing of large continuous genomic targets with double
      hybridization.
AB  - BACKGROUND: Targeted sequencing is a powerful tool with broad application in both
      basic and translational sciences. Relatively low on-target rates for most current
      targeted sequencing studies influence the required coverage and data quality for
      subsequent applications. RESULTS: We present an improved targeted sequencing
      method that uses two rounds of in solution hybridization with probes synthesized
      from genomic clone templates, termed dCATCH-Seq. Independent captures of two
      large continuous genomic regions across three cell types within the human major
      histocompatibility complex (MHC) that spans ~3.5 Mb and a ~250 kb region on
      chromosome 11 demonstrated that dCATCH-Seq was highly reproducible with ~95%
      capture specificity. Comprehensive analyses of sequencing data generated using
      the dCATCH-Seq approach also showed high accuracy in the detection of genetic
      variants and HLA typing. The double hybridization capture approach can also be
      coupled with bisulfite sequencing for DNA methylation profiling of both CpG and
      non-CpG sites. CONCLUSIONS: Altogether, dCATCH-Seq is a powerful and scalable
      targeted sequencing approach to investigate both genetic and epigenetic features.

PMID- 29061110
TI  - A rapid and accurate approach for prediction of interactomes from co-elution data
      (PrInCE).
AB  - BACKGROUND: An organism's protein interactome, or complete network of protein
      protein interactions, defines the protein complexes that drive cellular
      processes. Techniques for studying protein complexes have traditionally applied
      targeted strategies such as yeast two-hybrid or affinity purification-mass
      spectrometry to assess protein interactions. However, given the vast number of
      protein complexes, more scalable methods are necessary to accelerate interaction
      discovery and to construct whole interactomes. We recently developed a
      complementary technique based on the use of protein correlation profiling (PCP)
      and stable isotope labeling in amino acids in cell culture (SILAC) to assess
      chromatographic co-elution as evidence of interacting proteins. Importantly, PCP
      SILAC is also capable of measuring protein interactions simultaneously under
      multiple biological conditions, allowing the detection of treatment-specific
      changes to an interactome. Given the uniqueness and high dimensionality of co
      elution data, new tools are needed to compare protein elution profiles, control
      false discovery rates, and construct an accurate interactome. RESULTS: Here we
      describe a freely available bioinformatics pipeline, PrInCE, for the analysis of
      co-elution data. PrInCE is a modular, open-source library that is computationally
      inexpensive, able to use label and label-free data, and capable of detecting tens
      of thousands of protein-protein interactions. Using a machine learning approach,
      PrInCE offers greatly reduced run time, more predicted interactions at the same
      stringency, prediction of protein complexes, and greater ease of use over
      previous bioinformatics tools for co-elution data. PrInCE is implemented in
      Matlab (version R2017a). Source code and standalone executable programs for
      Windows and Mac OSX are available at https://github.com/fosterlab/PrInCE , where
      usage instructions can be found. An example dataset and output are also provided
      for testing purposes. CONCLUSIONS: PrInCE is the first fast and easy-to-use data
      analysis pipeline that predicts interactomes and protein complexes from co
      elution data. PrInCE allows researchers without bioinformatics expertise to
      analyze high-throughput co-elution datasets.

PMID- 29061108
TI  - Uncovering the embryonic development-related proteome and metabolome signatures
      in breast muscle and intramuscular fat of fast-and slow-growing chickens.
AB  - BACKGROUND: Skeletal muscle development is closely linked to meat production and
      its quality. This study is the first to quantify the proteomes and metabolomes of
      breast muscle in two distinct chicken breeds at embryonic day 12 (ED 12), ED 17,
      post-hatch D 1 and D 14 using mass spectrometry-based approaches. RESULTS:
      Results found that intramuscular fat (IMF) accumulation increased from ED 17 to D
      1 and that was exactly the opposite of when most obvious growth of muscle
      occurred (ED 12 - ED 17 and D 1 - D 14). For slow-growing Beijing-You chickens,
      Ingenuity Pathway Analysis of 77-99 differential abundance (DA) proteins and 63
      72 metabolites, indicated significant enrichment of molecules and pathways
      related to protein processing and PPAR signaling. For fast-growing Cobb chickens,
      analysis of 68-95 DA proteins and 56-59 metabolites demonstrated that molecules
      and pathways related to ATP production were significantly enriched after ED12.
      For IMF, several rate-limiting enzymes for beta-oxidation of fatty acid (ACADL,
      ACAD9, HADHA and HADHB) were identified as candidate biomarkers for IMF
      deposition in both breeds. CONCLUSIONS: This study found that ED 17 - D 1 was the
      earliest period for IMF accumulation. Pathways related to protein processing and
      PPAR signaling were enriched to support high capacity of embryonic IMF
      accumulation in Beijing-You. Pathways related to ATP production were enriched to
      support the fast muscle growth in Cobb. The beta-oxidation of fatty acid is
      identified as the key pathway regulating chicken IMF deposition at early stages.

PMID- 29061111
TI  - Normative prosthodontic care need: does it impact the daily life of young Saudis
      with high level of oral diseases? A cross sectional study.
AB  - BACKGROUND: Assessing the need for prosthodontic care previously included older
      age groups. There is less information about younger populations who may need this
      care because of high disease levels. The aim of this study was to assess the
      normative need for prosthodontic care in a young Saudi population with high oral
      disease levels, the associated factors and its impact on daily life. METHODS: A
      cross sectional study included Saudi adults in the Eastern Province in 2016. A
      questionnaire was used to assess personal background (confounders), risk factors
      affecting oral diseases (exposures) and the impact of oral problems on daily
      life. A clinical examination assessed tooth loss, the presence of prosthodontic
      appliances, the presence of untreated decay and need for periodontal care.
      Directed acyclic graphs identified the confounders to be included in regression
      models with separate outcomes: normative need for prosthodontic care (binary
      logistic model) and impact on 6 daily life aspects (ordinal regression models).
      RESULTS: Complete data were available for 574/ 700 = 82% and 46.7% needed
      prosthodontic care with 2 lost teeth on average among adults of mean age = 33.2
      years. The confounders controlled for the need for prosthodontic care included
      socioeconomic status (SES), dental visits last year and health insurance. The
      confounders for the impact on daily life included age and SES. In adjusted
      models, normative need for prosthodontic care was significantly associated with
      untreated decay (OR = 2.09, 95% C.I. = 1.37, 3.19). The impact on daily life was
      not significantly associated with prosthodontic care need but with untreated
      decay, especially sleeplessness (regression coefficient = 0.53, 95% C.I. = 0.02,
      1.04) and dropping daily activities (regression coefficient = 0.79, 95% C.I. =
      0.13, 1.46). In addition, the need for periodontal care was associated with food
      avoidance (regression coefficient = 0.73, 95% C.I. = 0.28, 1.18). CONCLUSIONS: In
      Saudi adults in the Eastern Province, there was a considerable normative need for
      prosthodontic care due to untreated decay. The impact on daily life was related
      to the underlying oral diseases rather than the need for prosthodontic care
      itself.

PMID- 29061113
TI  - The emerging roles of NGS-based liquid biopsy in non-small cell lung cancer.
AB  - The treatment paradigm of non-small cell lung cancer (NSCLC) has evolved into
      oncogene-directed precision medicine. Identifying actionable genomic alterations
      is the initial step towards precision medicine. An important scientific progress
      in molecular profiling of NSCLC over the past decade is the shift from the
      traditional piecemeal fashion to massively parallel sequencing with the use of
      next-generation sequencing (NGS). Another technical advance is the development of
      liquid biopsy with great potential in providing a dynamic and comprehensive
      genomic profiling of NSCLC in a minimally invasive manner. The integration of NGS
      with liquid biopsy has been demonstrated to play emerging roles in genomic
      profiling of NSCLC by increasing evidences. This review summarized the potential
      applications of NGS-based liquid biopsy in the diagnosis and treatment of NSCLC
      including identifying actionable genomic alterations, tracking spatiotemporal
      tumor evolution, dynamically monitoring response and resistance to targeted
      therapies, and diagnostic value in early-stage NSCLC, and discussed emerging
      challenges to overcome in order to facilitate clinical translation in future.

PMID- 29061114
TI  - Mortality in patients with Sanfilippo syndrome.
AB  - BACKGROUND: Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) is an
      inherited monogenic lysosomal storage disorder divided into subtypes A, B, C and
      D. Each subtype is characterized by deficiency of a different enzyme
      participating in metabolism of heparan sulphate. The resultant accumulation of
      this substrate in bodily tissues causes various malfunctions of organs,
      ultimately leading to premature death. Eighty-four, 24 and 5 death certificates
      of patients with Sanfilippo syndrome types A, B and C, respectively, were
      obtained from the Society of Mucopolysaccharide Diseases (UK) to better
      understand the natural course of these conditions, covering the years 1977-2007.
      RESULTS: In Sanfilippo syndrome type A mean age at death (+/- standard deviation)
      was 15.22 +/- 4.22 years, 18.91 +/- 7.33 years for patients with Sanfilippo
      syndrome type B and 23.43 +/- 9.47 years in Sanfilippo syndrome type C. Patients
      with Sanfilippo syndrome type A showed significant increase in longevity over the
      period of observation (p = 0.012). Survival rates of patients with Sanfilippo
      syndrome type B did not show a statistically significant improvement (p = 0.134).
      In Sanfilippo syndrome types A and B, pneumonia was identified as the leading
      cause of death. CONCLUSIONS: The analysis of 113 death certificates of patients
      with Sanfilippo syndrome in the UK has demonstrated that the longevity has
      improved significantly in patients with Sanfilippo syndrome type A over a last
      few decades. The numbers of patients with Sanfilippo syndrome types B and C were
      too small to identify any significant trend changes for these groups. Respiratory
      tract infections, notably pneumonia, remain the leading cause of mortality in
      Sanfilippo syndrome types A and B. The extended lifespans of patients with
      Sanfilippo syndrome type A were achieved despite the lack of therapies to target
      the primary insult or pathophysiology of the disease. However, the mean age at
      death of these patients remains low when compared with the general population.
      Therefore, there is an urgent need for effective disease-specific therapies to be
      developed so that the quality of life and survival of patients with Sanfilippo
      syndrome can be improved.

PMID- 29061112
TI  - Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in
      human neurodegenerative diseases.
AB  - The homeostasis of iron is vital to human health, and iron dyshomeostasis can
      lead to various disorders. Iron homeostasis is maintained by iron regulatory
      proteins (IRP1 and IRP2) and the iron-responsive element (IRE) signaling pathway.
      IRPs can bind to RNA stem-loops containing an IRE in the untranslated region
      (UTR) to manipulate translation of target mRNA. However, iron can bind to IRPs,
      leading to the dissociation of IRPs from the IRE and altered translation of
      target transcripts. Recently an IRE is found in the 5'-UTR of amyloid precursor
      protein (APP) and alpha-synuclein (alpha-Syn) transcripts. The levels of alpha
      Syn, APP and amyloid beta-peptide (Abeta) as well as protein aggregation can be
      down-regulated by IRPs but are up-regulated in the presence of iron accumulation.
      Therefore, inhibition of the IRE-modulated expression of APP and alpha-Syn or
      chelation of iron in patient's brains has therapeutic significance to human
      neurodegenerative diseases. Currently, new pre-drug IRE inhibitors with
      therapeutic effects have been identified and are at different stages of clinical
      trials for human neurodegenerative diseases. Although some promising drug
      candidates of chemical IRE inhibitors and iron-chelating agents have been
      identified and are being validated in clinical trials for neurodegenerative
      diseases, future studies are expected to further establish the clinical efficacy
      and safety of IRE inhibitors and iron-chelating agents in patients with
      neurodegenerative diseases.

PMID- 29061115
TI  - Comparative transcriptomic analyses of normal and malformed flowers in sugar
      apple (Annona squamosa L.) to identify the differential expressed genes between
      normal and malformed flowers.
AB  - BACKGROUND: Sugar apple (Annona squamosa L.), a popular fruit with high medicinal
      and nutritional properties, is widely cultivated in tropical South Asia and
      America. The malformed flower is a major cause for a reduction in production of
      sugar apple. However, little information is available on the differences between
      normal and malformed flowers of sugar apple. RESULTS: To gain a comprehensive
      perspective on the differences between normal and malformed flowers of sugar
      apple, cDNA libraries from normal and malformation flowers were prepared
      independently for Illumina sequencing. The data generated a total of 70,189,896
      reads that were integrated and assembled into 55,097 unigenes with a mean length
      of 783 bp. A large number of differentially expressed genes (DEGs) were
      identified. Among these DEGs, 701 flower development-associated transcript factor
      encoding genes were included. Furthermore, a large number of flowering- and
      hormone-related DEGs were also identified, and most of these genes were down
      regulated expressed in the malformation flowers. The expression levels of 15
      selected genes were validated using quantitative-PCR. The contents of several
      endogenous hormones were measured. The malformed flowers displayed lower
      endogenous hormone levels compared to the normal flowers. CONCLUSIONS: The
      expression data as well as hormone levels in our study will serve as a
      comprehensive resource for investigating the regulation mechanism involved in
      floral organ development in sugar apple.

PMID- 29061116
TI  - A genome-wide analysis of the small auxin-up RNA (SAUR) gene family in cotton.
AB  - BACKGROUND: Small auxin-up RNA (SAUR) gene family is the largest family of early
      auxin response genes in higher plants, which have been implicated in the
      regulation of multiple biological processes. However, no comprehensive analysis
      of SAUR genes has been reported in cotton (Gossypium spp.). RESULTS: In the
      study, we identified 145, 97, 214, and 176 SAUR homologous genes in the sequenced
      genomes of G. raimondii, G. arboreum, G. hirsutum, and G. barbadense,
      respectively. A phylogenetic analysis revealed that the SAUR genes can be
      classified into 10 groups. A further analysis of chromosomal locations and gene
      duplications showed that tandem duplication and segmental duplication events
      contributed to the expansion of the SAUR gene family in cotton. An exon-intron
      organization and motif analysis revealed the conservation of SAUR-specific
      domains, and the auxin responsive elements existed in most of the upstream
      sequences. The expression levels of 16 GhSAUR genes in response to an exogenous
      application of IAA were determined by a quantitative RT-PCR analysis. The genome
      wide RNA-seq data and qRT-PCR analysis of selected SAUR genes in developing
      fibers revealed their differential expressions. The physical mapping showed that
      20 SAUR genes were co-localized with fiber length quantitative trait locus (QTL)
      hotspots. Single nucleotide polymorphisms (SNPs) were detected for 12 of these 20
      genes between G. hirsutum and G. barbadense, but no SNPs were identified between
      two backcross inbred lines with differing fiber lengths derived from a cross
      between the two cultivated tetraploids. CONCLUSIONS: This study provides an
      important piece of genomic information for the SAUR genes in cotton and lays a
      solid foundation for elucidating the functions of SAUR genes in auxin signaling
      pathways to regulate cotton growth.

PMID- 29061117
TI  - Diatom flagellar genes and their expression during sexual reproduction in
      Leptocylindrus danicus.
AB  - BACKGROUND: Flagella have been lost in the vegetative phase of the diatom life
      cycle, but they are still present in male gametes of centric species, thereby
      representing a hallmark of sexual reproduction. This process, besides maintaining
      and creating new genetic diversity, in diatoms is also fundamental to restore the
      maximum cell size following its reduction during vegetative division.
      Nevertheless, sexual reproduction has been demonstrated in a limited number of
      diatom species, while our understanding of its different phases and of their
      genetic control is scarce. RESULTS: In the transcriptome of Leptocylindrus
      danicus, a centric diatom widespread in the world's seas, we identified 22
      transcripts related to the flagella development and confirmed synchronous
      overexpression of 6 flagellum-related genes during the male gamete formation
      process. These transcripts were mostly absent in the closely related species L.
      aporus, which does not have sexual reproduction. Among the 22 transcripts, L.
      danicus showed proteins that belong to the Intra Flagellar Transport (IFT)
      subcomplex B as well as IFT-A proteins, the latter previously thought to be
      absent in diatoms. The presence of flagellum-related proteins was also traced in
      the transcriptomes of several other centric species. Finally, phylogenetic
      reconstruction of the IFT172 and IFT88 proteins showed that their sequences are
      conserved across protist species and have evolved similarly to other phylogenetic
      marker genes. CONCLUSION: Our analysis describes for the first time the diatom
      flagellar gene set, which appears to be more complete and functional than
      previously reported based on the genome sequence of the model centric diatom,
      Thalassiosira pseudonana. This first recognition of the whole set of diatom
      flagellar genes and of their activation pattern paves the way to a wider
      recognition of the relevance of sexual reproduction in individual species and in
      the natural environment.

PMID- 29061118
TI  - High-resolution manometry in patients with and without globus pharyngeus and/or
      symptoms of laryngopharyngeal reflux.
AB  - BACKGROUND: Globus pharyngeus is common and has a low cure rate. Its etiology is
      complex and reported to be associated with laryngopharyngeal reflux (LPR).
      However, some patients with globus do not exhibit any reflux symptoms or respond
      to proton pump inhibitors (PPIs) treatments. The purpose of this study was to
      clarify the related risk factors of these patients with a final objective of
      improving the curative effect. METHODS: Forty two patients afflicted with globus
      pharyngeus (G group) and 38 patients without globus pharyngeus (NG group) were
      included in this study. According to the laryngopharyngeal Reflux Symptom Index
      and the response to PPIs treatments, the patients were further divided into
      reflux groups (G-R, NG-R) and non-reflux groups (G-NR, NG-NR). High Resolution
      Manometry (HRM) was performed to assess esophageal motility. Questionnaires,
      including categories such as life exposure factors, were conducted. RESULTS: a)
      The average resting and residual pressures of the upper esophageal sphincter
      (UES) in the G-NR group was higher than in the NG-NR and NG-R groups (P < 0.05).
      b) The average resting and residual pressures of the lower esophageal sphincter
      showed no differences between the G-NR group and the NG-NR group (P > 0.05). c)
      The esophageal distal contractile integral score of the G-NR group was not
      different from the NG-NR group (P > 0.05). d) Compared to the NG-NR group, the G
      NR group showed higher incidence of stress, smoking, drinking, high salt and
      anxiety (P < 0.05). CONCLUSIONS: Globus pharyngeus without LPR may occur due to
      high UES pressure. Stress, smoking, alcoholic drinking, high salt and anxiety may
      be its risk factors.

PMID- 29061119
TI  - Computer-controlled closed-loop drug infusion system for automated hemodynamic
      resuscitation in endotoxin-induced shock.
AB  - BACKGROUND: Hemodynamic resuscitation in septic shock requires aggressive fluid
      replacement and appropriate use of vasopressors to optimize arterial pressure
      (AP) and cardiac output (CO). Because responses to these drugs vary between
      patients and within patient over time, strict monitoring of patient condition and
      repetitive adjustment of drug dose are required. This task is time and labor
      consuming, and is associated with poor adherence to resuscitation guidelines. To
      overcome this issue, we developed a computer-controlled closed-loop drug infusion
      system for automated hemodynamic resuscitation in septic shock, and evaluated the
      performance of the system in a canine model of endotoxin shock. METHODS: Our
      system monitors AP, CO and central venous pressure, and computes arterial
      resistance (R), stressed blood volume (V) and Frank-Starling slope of left
      ventricle (S). The system controls R with noradrenaline (NA), and V with Ringer's
      acetate solution (RiA), thereby controlling AP and CO. In 4 dogs, AP and CO were
      measured invasively. In another 4 dogs, AP and CO were measured less invasively
      using clinically acceptable modalities, aiming to make the system clinically
      feasible. In all 8 dogs, endotoxin shock was induced by injecting Escherichia
      coli lipopolysaccharide, which significantly decreased AP from 95 (91-108) to 43
      (39-45) mmHg, and CO from 112 (104-142) to 62 (51-73) ml.min-1.kg-1. The system
      was then connected to the dogs, and activated. System performance was observed
      over a period of 4 h. RESULTS: Our system immediately started infusions of NA and
      RiA. Within 40 min, RiA increased V to target level, and NA maintained R at
      target level, while S was concomitantly increased. These resulted in restoration
      of AP to 70 (69-71) mmHg and CO to 130 (125-138) ml.min-1.kg-1. Median of
      absolute performance error, an index of precision of control, was small in AP
      [2.5 (2.1-4.5) %] and CO [2.4 (1.4-5.5) %], which were not increased even when
      the variables were measured less invasively. CONCLUSIONS: In a canine model of
      endotoxin shock, our system automatically improved and maintained AP and CO at
      their target values with small performance error. Our system is potentially an
      attractive clinical tool for rescuing patients with septic shock.

PMID- 29061120
TI  - Transcriptomic response of the Antarctic pteropod Limacina helicina antarctica to
      ocean acidification.
AB  - BACKGROUND: Ocean acidification (OA), a change in ocean chemistry due to the
      absorption of atmospheric CO2 into surface oceans, challenges biogenic
      calcification in many marine organisms. Ocean acidification is expected to
      rapidly progress in polar seas, with regions of the Southern Ocean expected to
      experience severe OA within decades. Biologically, the consequences of OA
      challenge calcification processes and impose an energetic cost. RESULTS: In order
      to better characterize the response of a polar calcifier to conditions of OA, we
      assessed differential gene expression in the Antarctic pteropod, Limacina
      helicina antarctica. Experimental levels of pCO2 were chosen to create both
      contemporary pH conditions, and to mimic future pH expected in OA scenarios.
      Significant changes in the transcriptome were observed when juvenile L. h.
      antarctica were acclimated for 21 days to low-pH (7.71), mid-pH (7.9) or high-pH
      (8.13) conditions. Differential gene expression analysis of individuals
      maintained in the low-pH treatment identified down-regulation of genes involved
      in cytoskeletal structure, lipid transport, and metabolism. High pH exposure led
      to increased expression and enrichment for genes involved in shell formation,
      calcium ion binding, and DNA binding. Significant differential gene expression
      was observed in four major cellular and physiological processes: shell formation,
      the cellular stress response, metabolism, and neural function. Across these
      functional groups, exposure to conditions that mimic ocean acidification led to
      rapid suppression of gene expression. CONCLUSIONS: Results of this study
      demonstrated that the transcriptome of the juvenile pteropod, L. h. antarctica,
      was dynamic and changed in response to different levels of pCO2. In a global
      change context, exposure of L. h. antarctica to the low pH, high pCO2 OA
      conditions resulted in a suppression of transcripts for genes involved in key
      physiological processes: calcification, metabolism, and the cellular stress
      response. The transcriptomic response at both acute and longer-term acclimation
      time frames indicated that contemporary L. h. antarctica may not have the
      physiological plasticity necessary for adaptation to OA conditions expected in
      future decades. Lastly, the differential gene expression results further support
      the role of shelled pteropods such as L. h. antarctica as sentinel organisms for
      the impacts of ocean acidification.

PMID- 29061121
TI  - Fecal calprotectin predicts complete mucosal healing and better correlates with
      the ulcerative colitis endoscopic index of severity than with the Mayo endoscopic
      subscore in patients with ulcerative colitis.
AB  - BACKGROUND: We aimed to evaluate the role of fecal calprotectin (FC) as a
      noninvasive marker for the disease activity of ulcerative colitis (UC) in a
      Korean cohort. METHODS: A total of 181 fecal samples were collected from 181
      consecutive UC patients between April 2015 and September 2016. FC levels were
      measured using the Quantum Blue(r) Calprotectin rapid test. The laboratory test
      results, partial Mayo Score (pMS), and colonoscopic imaging findings at FC level
      measurement were retrospectively reviewed. The Mayo endoscopic subscore (MES) and
      UC endoscopic index of severity (UCEIS) were graded by 2 certified endoscopists
      after training with 50 other cases. RESULTS: The FC levels were significantly
      correlated with pMS (Spearman correlation coefficient r = 0.428, p < 0.001), MES
      (r = 0.304, p < 0.001), UCEIS (r = 0.430, p < 0.001), and CRP (r = 0.379, p <
      0.001). FC levels exhibited a significantly better correlation with UCEIS than
      with MES (Meng's z = - 2.457, p = 0.01). The FC cut-off level of 187.0 mg/kg
      indicated complete mucosal healing (MES = 0; UCEIS =0) with a sensitivity and
      specificity of 0.857 and 0.891, respectively (area under the curve, 0.883; 95%
      confidence interval, 0.772-1.000). CONCLUSION: The FC level is significantly
      correlated with the clinical disease activity index, endoscopic indices, and
      serum inflammatory biomarkers in a Korean UC cohort. FC is highly predictive of
      complete mucosal healing in UC. UCEIS exhibits a stronger correlation with the FC
      level, as compared to MES. Thus, FC could be used as a reliable noninvasive
      indicator for evaluating disease activity and mucosal healing in UC.

PMID- 29061122
TI  - Metabolic differentiation of surface and invasive cells of yeast colony biofilms
      revealed by gene expression profiling.
AB  - BACKGROUND: Yeast infections are often connected with formation of biofilms that
      are extremely difficult to eradicate. An excellent model system for deciphering
      multifactorial determinants of yeast biofilm development is the colony biofilm,
      composed of surface ("aerial") and invasive ("root") cells. While surface cells
      have been partially analyzed before, we know little about invasive root cells. In
      particular, information on the metabolic, chemical and morphogenetic properties
      of invasive versus surface cells is lacking. In this study, we used a new
      strategy to isolate invasive cells from agar and extracellular matrix, and
      employed it to perform genome wide expression profiling and biochemical analyses
      of surface and invasive cells. RESULTS: RNA sequencing revealed expression
      differences in 1245 genes with high statistical significance, indicating large
      genetically regulated metabolic differences between surface and invasive cells.
      Functional annotation analyses implicated genes involved in stress defense,
      peroxisomal fatty acid beta-oxidation, autophagy, protein degradation, storage
      compound metabolism and meiosis as being important in surface cells. In contrast,
      numerous genes with functions in nutrient transport and diverse synthetic
      metabolic reactions, including genes involved in ribosome biogenesis,
      biosynthesis and translation, were found to be important in invasive cells.
      Variation in gene expression correlated significantly with cell-type specific
      processes such as autophagy and storage compound accumulation as identified by
      microscopic and biochemical analyses. Expression profiling also provided
      indications of cell-specific regulations. Subsequent knockout strain analyses
      identified Gip2p, a regulatory subunit of type 1 protein phosphatase Glc7p, to be
      essential for glycogen accumulation in surface cells. CONCLUSIONS: This is the
      first study reporting genome wide differences between surface and invasive cells
      of yeast colony biofilms. New findings show that surface and invasive cells
      display very different physiology, adapting to different conditions in different
      colony areas and contributing to development and survival of the colony biofilm
      as a whole. Notably, surface and invasive cells of colony biofilms differ
      significantly from upper and lower cells of smooth colonies adapted to plentiful
      laboratory conditions.

PMID- 29061123
TI  - Genomic evaluation for a three-way crossbreeding system considering breed-of
      origin of alleles.
AB  - BACKGROUND: Genomic prediction of purebred animals for crossbred performance can
      be based on a model that estimates effects of single nucleotide polymorphisms
      (SNPs) in purebreds on crossbred performance. For crossbred performance, SNP
      effects might be breed-specific due to differences between breeds in allele
      frequencies and linkage disequilibrium patterns between SNPs and quantitative
      trait loci. Accurately tracing the breed-of-origin of alleles (BOA) in three-way
      crosses is possible with a recently developed procedure called BOA. A model that
      accounts for breed-specific SNP effects (BOA model), has never been tested
      empirically on a three-way crossbreeding scheme. Therefore, the objectives of
      this study were to evaluate the estimates of variance components and the
      predictive accuracy of the BOA model compared to models in which SNP effects for
      crossbred performance were assumed to be the same across breeds, using either
      breed-specific allele frequencies ([Formula: see text] model) or allele
      frequencies averaged across breeds ([Formula: see text] model). In this study, we
      used data from purebred and three-way crossbred pigs on average daily gain (ADG),
      back fat thickness (BF), and loin depth (LD). RESULTS: Estimates of variance
      components for crossbred performance from the BOA model were mostly similar to
      estimates from models [Formula: see text] and [Formula: see text]. Heritabilities
      for crossbred performance ranged from 0.24 to 0.46 between traits. Genetic
      correlations between purebred and crossbred performance ([Formula: see text])
      across breeds ranged from 0.30 to 0.62 for ADG and from 0.53 to 0.74 for BF and
      LD. For ADG, prediction accuracies of the BOA model were higher than those of the
      [Formula: see text] and [Formula: see text] models, with significantly higher
      accuracies only for one maternal breed. For BF and LD, prediction accuracies of
      models [Formula: see text] and [Formula: see text] were higher than those of the
      BOA model, with no significant differences. Across all traits, models [Formula:
      see text] and [Formula: see text] yielded similar predictions. CONCLUSIONS: The
      BOA model yielded a higher prediction accuracy for ADG in one maternal breed,
      which had the lowest [Formula: see text] (0.30). Using the BOA model was
      especially relevant for traits with a low [Formula: see text]. In all other
      cases, the use of crossbred information in models [Formula: see text] and
      [Formula: see text], does not jeopardize predictions and these models are more
      easily implemented than the BOA model.

PMID- 29061124
TI  - Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness
      and renal resistive index in type 2 diabetic patients: a pilot study.
AB  - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP)
      and renal and cardiovascular events in patients with type 2 diabetes through not
      fully elucidated mechanisms. Aim of this study was to investigate whether
      dapagliflozin is able to acutely modify systemic and renal vascular function, as
      well as putative mechanisms. METHODS: Neuro-hormonal and vascular variables,
      together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water
      clearance were assessed before and after a 2-day treatment with dapagliflozin 10
      mg QD in sixteen type 2 diabetic patients; data were compared with those obtained
      in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery
      endothelium-dependent and independent vasodilation (by flow-mediated dilation)
      and pulse wave velocity were assessed. Renal resistive index was obtained at rest
      and after glyceryl trinitrate administration. Differences were analysed by
      repeated measures ANOVA, considering treatment as between factor and time as
      within factor; Bonferroni post hoc comparison test was also used. RESULTS:
      Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a
      similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium
      were also increased. 24 h urinary sodium and fasting blood glucose were
      unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes.
      Flow-mediated dilation was significantly increased (2.8 +/- 2.2 to 4.0 +/- 2.1%,
      p < 0.05), and pulse-wave-velocity was reduced (10.1 +/- 1.6 to 8.9 +/- 1.6 m/s,
      p < 0.05), even after correction for mean BP. Renal resistive index was reduced
      (0.62 +/- 0.04 to 0.59 +/- 0.05, p < 0.05). These vascular modifications were not
      observed in hydrochlorothiazide-treated individuals. CONCLUSIONS: An acute
      treatment with dapagliflozin significantly improves systemic endothelial
      function, arterial stiffness and renal resistive index; this effect is
      independent of changes in BP and occurs in the presence of stable natriuresis,
      suggesting a fast, direct beneficial effect on the vasculature, possibly mediated
      by oxidative stress reduction.

PMID- 29061125
TI  - Whether intermediate-risk stage 1A, grade 1/2, endometrioid endometrial cancer
      patients with lesions larger than 2 cm warrant lymph node dissection?
AB  - BACKGROUND: Our research aimed to investigate whether lymphadenectomy was
      required in patients with intermediate-risk endometrioid endometrial cancer
      (EEC). METHODS: Between 1989 and 2015, 1009 patients with intermediate-risk EEC:
      grade 1 or 2 tumor, <50% myometrial invasion, and a tumor diameter >= 2 cm and
      818 low-risk patients with grade 1 or 2 tumor, <50% myometrial invasion, and a
      tumor diameter < 2 cm were enrolled in this study. The rate and risk factors of
      node metastasis were evaluated and compared between the two risk groups. Survival
      data were analyzed in patients with intermediate-risk EEC with or without
      lymphadenectomy. RESULTS: In all, 624 of 1009 (61.8%) patients with intermediate
      risk EEC underwent pelvic +/- para-aortic lymphadenectomy with a nodal metastasis
      rate of 1.9% (12/624), whereas 394 of 818 (48.2%) patients with low-risk EEC
      underwent pelvic +/- para-aortic lymphadenectomy with a nodal metastasis rate of
      0.3% (1/394) (p = 0.021). Notably, intermediate-risk EEC patients with a
      microcystic, elongated and fragmented (MELF) pattern of invasion, lymphatic
      vascular space invasion (LVSI), diffuse lesions, or lesions located in the cornua
      were more likely to have node metastasis. The 5-year overall cancer-related
      survival and the recurrence-free survival rates of the 742 intermediate-risk EEC
      patients who were followed for more than 3 years were 99.4% and 94.7%,
      respectively. In intermediate-risk group, 6 patients (6/443, 1.4%) with
      lymphadenectomy and 9 patients (9/299, 3.0%) without lymphadenectomy recurred,
      with a mean recurrence time of 38.3 and 18.7 months respectively. The five-year
      overall and recurrence-free survival rates of intermediate-risk patients with and
      without lymphadenectomy were similar (100% vs 98.9%, p = 0.351; 95.2% vs 93.3%, p
      = 0.464). CONCLUSION: Patients with intermediate-risk EEC have low nodal
      metastasis rate and a favorable outcome whether lymphadenectomy is performed or
      not. Omission of lymphadenectomy may be a reasonable option in the surgical
      management of patients with intermediate-risk EEC.

PMID- 29061126
TI  - Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in
      patients presenting in primary care with lower abdominal symptoms: a systematic
      review conducted to inform new NICE DG30 diagnostic guidance.
AB  - BACKGROUND: This study has attempted to assess the effectiveness of quantitative
      faecal immunochemical tests (FIT) for triage of people presenting with lower
      abdominal symptoms, where a referral to secondary care for investigation of
      suspected colorectal cancer (CRC) is being considered, particularly when the 2
      week criteria are not met. METHODS: We conducted a systematic review following
      published guidelines for systematic reviews of diagnostic tests. Twenty-one
      resources were searched up until March 2016. Summary estimates were calculated
      using a bivariate model or a random-effects logistic regression model. RESULTS:
      Nine studies are included in this review. One additional study, included in our
      systematic review, was provided as 'academic in confidence' and cannot be
      described herein. When FIT was based on a single faecal sample and a cut-off of
      10 MUg Hb/g faeces, sensitivity estimates indicated that a negative result using
      either the OC-Sensor or HM-JACKarc may be adequate to rule out nearly all CRC;
      the summary estimate of sensitivity for the OC-Sensor was 92.1% (95% confidence
      interval, CI 86.9-95.3%), based on four studies (n = 4091 participants, 176 with
      CRC), and the only study of HM-JACKarc to assess the 10 MUg Hb/g faeces cut-off
      (n = 507 participants, 11 with CRC) reported a sensitivity of 100% (95% CI 71.5
      100%). The corresponding specificity estimates were 85.8% (95% CI 78.3-91.0%) and
      76.6% (95% CI 72.6-80.3%), respectively. When the diagnostic criterion was
      changed to include lower grades of neoplasia, i.e. the target condition included
      higher risk adenoma (HRA) as well as CRC, the rule-out performance of both FIT
      assays was reduced. CONCLUSIONS: There is evidence to suggest that triage using
      FIT at a cut-off around 10 MUg Hb/g faeces has the potential to correctly rule
      out CRC and avoid colonoscopy in 75-80% of symptomatic patients. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO 42016037723.

PMID- 29061127
TI  - The underlying reasons for very high levels of bed net use, and higher malaria
      infection prevalence among bed net users than non-users in the Tanzanian city of
      Dar es Salaam: a qualitative study.
AB  - BACKGROUND: Bed nets reduce malaria-related illness and deaths, by forming a
      protective barrier around people sleeping under them. When impregnated with long
      lasting insecticide formulations they also repel or kill mosquitoes attempting to
      feed upon sleeping humans, and can even suppress entire populations of malaria
      vectors that feed predominantly upon humans. Nevertheless, an epidemiological
      study in 2012 demonstrated higher malaria prevalence among bed net users than non
      users in urban Dar es Salaam, Tanzania. METHODS: Focus group discussions were
      conducted with women from four selected wards of Dar es Salaam city, focusing on
      four major themes relating to bed net use behaviours: (1) reasons for bed net
      use, (2) reasons for not using bed nets, (3) stimuli or reminders for people to
      use a bed net (4) perceived reasons for catching malaria while using a bed net.
      An analytical method by framework grouping of relevant themes was used address
      key issues of relevance to the study objectives. Codes were reviewed and grouped
      into categories and themes. RESULTS: All groups said the main reason for bed net
      use was protection against malaria. Houses with well-screened windows, with doors
      that shut properly, and that use insecticidal sprays against mosquitoes, were
      said not to use bed nets, while frequent attacks from malaria was the main
      stimulus for people to use bed nets. Various reasons were mentioned as potential
      reasons that compromise bed net efficacy, the most common of which were: (1) bed
      net sharing by two or more people, especially if one occupant tends to come to
      bed late at night, and does not tuck in the net 71%; (2) one person shares the
      bed but does not use the net, moving it away from the side on which s/he sleeps
      68%; (3) ineffective usage habits, called ulalavi, in which a sprawling sleeper
      either touches the net while sleeping up against it or leaves a limb hanging
      outside of it 68%. Less common reasons mentioned included: (1) Small bed nets
      which become un-tucked at night (31%); (2) Bed nets with holes large enough to
      allow mosquitoes to pass (28%); and (3) Going to bed late after already being
      bitten outdoors (24%). CONCLUSIONS: Behaviours associated with bed net use like;
      bed sharing, bed net non compliant-bedfellow, sleeping pattern like ulalavi and
      some physical bed net attributes compromise its effectiveness and supposedly
      increase of malaria infection to bed net users. While some well-screened houses
      looked to instigate low malaria prevalence to non-bed net users.

PMID- 29061128
TI  - Effects of a multi-level intervention on the pattern of physical activity among
      in-school adolescents in Oyo state Nigeria: a cluster randomised trial.
AB  - BACKGROUND: Physical inactivity contributes to the global burden of non
      communicable diseases. The pattern of physical activity in adulthood are often
      established during adolescence and sedentary behaviours in the early years could
      influence the development of diseases later in life. Studies on physical activity
      in Nigeria have focused largely on individual behaviours and the effects of
      school-based interventions have not been well investigated. The aim of the
      proposed study is to identify factors influencing; and evaluate the effects of a
      multi-level intervention on the physical activity behaviours of in-school
      adolescents in Oyo state, Nigeria. METHODS: The study will adopt a cluster
      randomised controlled trial design and schools will serve as the unit of
      randomisation. The sample size is 1000 in-school adolescents aged 10-19 years.
      The study will be guided by the socio-ecological model and theory of reasoned
      action and baseline data will be obtained through a mixed methods approach
      comprising a cross sectional survey to document the self-reported physical
      activity levels coupled with objectively measured physical activity levels using
      pedometers for a subset of the sample. Other measurements including weight,
      height, waist and hip circumferences, fitness level using the 20-m shuttle run
      test (20-mSRT) and blood pressure will be obtained. The schools' built
      environment and policy support for physical activity will be assessed using
      structured questionnaires coupled with key informant interviews and focus group
      discussions with the school authorities. Baseline findings will guide the design
      and implementation of a 12-week multi-level intervention. The primary outcome
      measures are self-reported and 7-day objectively measured physical activity.
      Other secondary outcome measures are body-mass-index for age, waist-to-hip ratio,
      cardioresiratory fitness and blood pressure. The association between behavioural
      factors and physical activity levels will be assessed. Follow-up measurements
      will be taken immediately after the intervention and 3-months post intervention.
      DISCUSSION: Physical activity behaviours of adolescents in Nigeria are influenced
      by multiple factors. There is an urgent need for effective school-based
      interventions with a potential to improve the physical activity behaviours of
      adolescents in Nigeria and other low and middle income countries. TRIAL
      REGISTRATION: Pan African Clinical Trial Registry. TRIAL REGISTRATION NUMBER:
      PACTR201706002224335 , registered 26 June 2017.

PMID- 29061129
TI  - Antipsychotics and dementia in Canada: a retrospective cross-sectional study of
      four health sectors.
AB  - BACKGROUND: Antipsychotic medications are not recommended for the management of
      symptoms of dementia, particularly among persons with no behavioral or
      psychological symptoms. We examine patterns of antipsychotic medication use among
      persons with dementia across health sectors in Canada, with a focus on factors
      related to use among those without behavioral or psychotic symptoms. METHODS:
      Using a retrospective cross-sectional design, this study examines antipsychotic
      use among adults aged 65 or older with dementia in home care (HC), complex
      continuing care (CCC), long-term care (LTC), and among alternate level care
      patients in acute hospitals (ALC). Using clinical data from January 1, 2009 to
      December 31, 2014, the prevalence of antipsychotic medication use was estimated
      by the presence of behavioral and psychotic symptoms. Logistic regression was
      used to identify sector specific factors associated with antipsychotic use in the
      absence of behavioral and psychotic symptoms. RESULTS: The total prevalence of
      antipsychotic use among older adults with dementia was 26% in HC, 54% in ALC, 41%
      in CCC, and 48% in LTC. This prevalence ranged from 38% (HC) to 73% (ALC) for
      those with both behavioral and psychotic symptoms and from 15% (HC) to 31% (ALC)
      among those with no symptoms. The regression models identified a number of
      variables were related to antipsychotic use in the absence of behavior or
      psychotic symptoms, such as bipolar disorder (OR = 6.63 in CCC; OR = 5.52 in
      LTC), anxious complaints (OR = 1.54 in LTC to 2.01 in CCC), and wandering (OR =
      1.83 in ALC). CONCLUSIONS: Potentially inappropriate use of antipsychotic
      medications is prevalent among older adults with dementia across health sectors.
      The variations in prevalence observed from community to facility based care
      suggests that system issues may exist in appropriately managing persons with
      dementia.

PMID- 29061130
TI  - 18F- FDG PET/CT helps differentiate autoimmune pancreatitis from pancreatic
      cancer.
AB  - BACKGROUND: 18F-FDG PET/CT could satisfactorily show pancreatic and extra
      pancreatic lesions in AIP, which can be mistaken for pancreatic cancer (PC). This
      study aimed to identify 18F-FDG PET/CT findings that might differentiate AIP from
      PC. METHODS: FDG-PET/CT findings of 26 AIP and 40 PC patients were reviewed.
      Pancreatic and extra-pancreatic lesions related findings, including maximum
      standardized uptake values (SUVmax) and patterns of FDG uptake, were identified
      and compared. RESULTS: All 26 patients with AIP had increased pancreatic FDG
      uptake. Focal abnormal pancreatic FDG activities were found in 38/40 (95.00%) PC
      patients, while longitudinal were found in 18/26 (69.23%) AIP patients. SUVmax
      was significantly different between AIP and PC, both in early and delayed PET/CT
      scans (p < 0.05). AUCs were 0.700 (early SUVmax), 0.687 (delayed SUVmax), 0.683
      (early lesions/liver SUVmax), and 0.715 (delayed lesion/liver SUVmax). Bile duct
      related abnormalities were found in 12/26 (46.15%) AIP and 10/40 (25.00%) PC
      patients, respectively. Incidentally, salivary and prostate gland SUVmax in AIP
      patients were higher compared with those of PC patients (p < 0.05). In males,an
      inverted "V" shaped high FDG uptake in the prostate was more frequent in AIP than
      PC patients (56.00%, 14/25 vs. 5.71%, 2/35). Increased FDG activity in extra
      pancreatic bile duct was present in 4/26 of AIP patients, while was observed in
      none of the PC patients. Only in AIP patients, both diffuse pancreatic FDG
      accumulation and increased inverted "V" shaped FDG uptake in the prostate could
      be found simultaneously. CONCLUSIONS: 18F-FDG PET/CT findings might help
      differentiate AIP from PC.

PMID- 29061132
TI  - Depression among inmates in a regional prison of eastern Nepal: a cross-sectional
      study.
AB  - BACKGROUND: Depression is the most common form of mental disorder among inmates,
      with a prevalence much higher than in the general population. This study aims to
      estimate the prevalence of depression among inmates and identify factors
      associated with it. METHODS: This cross-sectional study was conducted in Jhumka
      Regional Prison, the largest prison in eastern Nepal, from September 2014 to
      August 2015. A total of 434 randomly selected inmates were interviewed using a
      semi-structured questionnaire examining socio-demographic characteristics,
      detention status, self-reported health problems, substance use status, and
      suicidal ideation. Depression was screened using the Center for Epidemiologic
      Studies Depression scale. Chi-square tests and multiple logistic regression
      analysis were applied to determine the association between depression and related
      variables. RESULTS: The mean age of the participants was 35.7 years (SD 13.3).
      The prevalence of depression among the inmates was 35.3%. Approximately 2.3%
      reported suicidal ideation during imprisonment and 0.9% had attempted suicide
      inside the prison. In bivariate analysis, depression was significantly associated
      with previous incarceration (OR = 1.91, 95% CI = 1.05-3.47, p = 0.033), poor self
      rated health (OR = 1.75, 95% CI = 1.16-2.64, p = 0.007), frequent appointments
      when encountering health problems (OR = 1.66, 95% CI = 1.06-2.61, p = 0.028),
      suicidal ideation (OR = 4.44, 95%CI = 1.13-17.44, p = 0.038) and loss of weight
      (OR = 1.49, 95% CI = 1.00-2.23, p = 0.049). However, only previous incarceration
      (AOR = 1.97, 95% CI = 1.04-3.74, p = 0.037) and frequent appointments when
      encountering health problems (AOR = 1.61, 95% CI = 1.01-2.57, p = 0.046) remained
      significant in a multivariate model. CONCLUSIONS: This study showed a high rate
      of depression among inmates in Nepal. The results suggest a need for psychiatric
      and rehabilitative care in correctional settings to improve the health status of
      the inmates.

PMID- 29061131
TI  - Proguanil and cycloguanil are organic cation transporter and multidrug and toxin
      extrusion substrates.
AB  - BACKGROUND: Malaria, HIV/AIDS, and tuberculosis endemic areas show considerable
      geographical overlap, leading to incidence of co-infections. This requires
      treatment with multiple drugs, potentially causing adverse drug-drug interactions
      (DDIs). As anti-malarials are generally positively charged at physiological pH,
      they are likely to interact with human organic cation transporters 1 and 2 (OCT1
      and OCT2). These transporters are involved in the uptake of drugs into
      hepatocytes and proximal tubule cells for subsequent metabolic conversion or
      elimination. This efflux of cationic drugs from hepatocytes and proximal tubule
      cells into bile and urine can be mediated by multidrug and toxin extrusion 1 and
      2-K (MATE1 and MATE2-K) transporters, respectively. METHODS: Here, the
      interaction of anti-malarials with these transporters was studied in order to
      predict potential DDIs. Using baculovirus-transduced HEK293 cells transiently
      expressing human OCT1, OCT2, MATE1 and MATE2K uptake and inhibition was studied
      by a range of anti-malarials. RESULTS: Amodiaquine, proguanil, pyrimethamine and
      quinine were the most potent inhibitors of 4-(4-(dimethylamino)styryl)-N
      methylpyridinium iodide (ASP) transport, a known substrate of OCT1/2, resulting
      in half maximal inhibitory concentrations (IC50) of 11, 13, 1.6, and 3.4 uM,
      respectively. Only quinine had a drug-drug index higher than the cut-off value of
      0.1 for OCT2, therefore, in vivo pharmacokinetic studies focusing on DDIs
      involving this compound and other OCT2-interacting drugs are warranted.
      Furthermore, proguanil appeared to be a substrate of OCT1 and OCT2 with
      affinities of 8.1 and 9.0 uM, respectively. Additionally, MATE1 and MATE2-K were
      identified as putative transport proteins for proguanil. Finally, its metabolite
      cycloguanil was also identified as an OCT1, OCT2, MATE1 and MATE2-K substrate.
      CONCLUSION: Anti-malarials can reduce OCT1 and OCT2 transport activity in vitro.
      Furthermore, proguanil and cycloguanil were found to be substrates of OCT1, OCT2,
      MATE1 and MATE2-K, highlighting the importance of these transporters in
      distribution and excretion. As these compounds shares substrate overlap with
      metformin DDIs can be anticipated during concurrent treatment.

PMID- 29061133
TI  - Factors associated with population coverage of targeted malaria elimination (TME)
      in southern Savannakhet Province, Lao PDR.
AB  - BACKGROUND: Targeted malaria elimination (TME) in Lao PDR (Laos) included three
      rounds of mass drug administrations (MDA) against malaria followed by quarterly
      blood surveys in two villages in Nong District at Savannakhet Province. The
      success of MDA largely depends upon the efficacy of the anti-malarial drug
      regimen, local malaria epidemiology and the population coverage. In order to
      explore the reasons for participation in TME, a quantitative survey was conducted
      after the completion of the three rounds of MDA. METHODS: The survey was
      conducted in two villages with a total of 158 households in July and August 2016.
      Among the 973 villagers eligible for participation in the MDA, 158 (16.2%) adults
      (> 18 years) were selected, one each from every household for the interviews
      using a quantitative questionnaire. RESULTS: 150/158 (94.9%) respondents
      participated at least in one activity (taking medicine or testing their blood) of
      TME. 141/150 (94.0%) respondents took part in the MDA and tested their blood in
      all three rounds. 17/158 (10.7%) were partial or non-participants in three rounds
      of MDA. Characteristics of respondents which were independently associated with
      completion of three rounds of MDA included: attending TME meetings [AOR = 12.0
      (95% CI 1.1-20.5) (p = 0.03)], knowing that malaria can be diagnosed through
      blood tests [AOR = 5.6 (95% CI 1.0-32.3) (p = 0.05)], all members from household
      participated [AOR = 4.2 (95% CI 1.3-14.0) (p = 0.02)], liking all aspects of TME
      [AOR = 17.2 (95% CI 1.6-177.9) (p = 0.02)] and the perception that TME was
      important [AOR = 14.9 (95% CI 1.3-171.2) (p = 0.03)]. CONCLUSION: Complete
      participation in TME was significantly associated with participation in community
      engagement activities, knowledge that the blood tests were for malaria diagnosis,
      family members' participation at TME and perceptions that TME was worthwhile. A
      responsive approach to community engagement that includes formative research and
      the involvement of community members may increase the uptake of the intervention.

PMID- 29061134
TI  - A birth cohort study in the Middle East: the Qatari birth cohort study (QBiC)
      phase I.
AB  - BACKGROUND: The latest scientific reports raise concerns about the rapidly
      increasing burden of chronic diseases in the state of Qatar. Pregnant Qatari
      women often confront complications during pregnancy including gestational
      diabetes, hypertension, abortion and stillbirth. The investigation of early life
      environmental, genetic, nutritional and social factors that may affect lifelong
      health is of great importance. Birth cohort studies offer a great opportunity to
      address early life hazards and their possible long lasting effects on health.
      METHODS/DESIGN: The Qatari Birth Cohort study is the first mother-child cohort
      study in the Middle East Area that aims to assess the synergetic role of
      environmental exposure and genetic factors in the development of chronic disease
      and monitor woman and child health and/or obstetric characteristics with high
      prevalence. The present manuscript describes the recruitment phase of the study
      (duration: 2 years; expected number: 3000 families), where the pregnant Qatari
      women and their husbands are being contacted before the 15th week of gestation at
      the Primary Health Care Centers. The consented participants are interviewed to
      obtain information on several factors (sociodemographic characteristics, dietary
      habits, occupational/environmental exposure) and maternal characteristics are
      assessed based on anthropometric measurements, spirometry, and blood pressure.
      Pregnant women are invited to provide biological samples (blood and urine) in
      each trimester of their pregnancy, as well as cord blood at delivery. Fathers are
      also asked to provide biological samples. DISCUSSION: The present study provides
      invaluable insights into a wide range of early life factors affecting human
      health. With a geographical focus on the Middle East, it will be a resource for
      information to the wider scientific community and will allow the formulation of
      effective policies with a primary focus on public health interventions for
      maternal and child health.

PMID- 29061135
TI  - Prognostic factors for recovery following acute lateral ankle ligament sprain: a
      systematic review.
AB  - BACKGROUND: One-third of individuals who sustain an acute lateral ankle ligament
      sprain suffer significant disability due to pain, functional instability,
      mechanical instability or recurrent sprain after recovery plateaus at 1 to 5
      years post injury. The identification of early prognostic factors associated with
      poor recovery may provide an opportunity for early-targeted intervention and
      improve outcome. METHODS: We performed a comprehensive search of AMED, EMBASE,
      Psych Info, CINAHL, SportDiscus, PubMed, CENTRAL, PEDro, OpenGrey, abstracts and
      conference proceedings from inception to September 2016. Prospective studies
      investigating the association between baseline prognostic factors and recovery
      over time were included. Two independent assessors performed the study selection,
      data extraction and quality assessment of the studies. A narrative synthesis is
      presented due to inability to meta-analyse results due to clinical and
      statistical heterogeneity. RESULTS: The search strategy yielded 3396
      titles/abstracts after duplicates were removed. Thirty-six full text articles
      were then assessed, nine of which met the study inclusion criteria. Six were
      prospective cohorts, and three were secondary analyses of randomised controlled
      trials. Results are presented for nine studies that presented baseline prognostic
      factors for recovery after an acute ankle sprain. Age, female gender, swelling,
      restricted range of motion, limited weight bearing ability, pain (at the medial
      joint line and on weight-bearing dorsi-flexion at 4 weeks, and pain at rest at 3
      months), higher injury severity rating, palpation/stress score, non-inversion
      mechanism injury, lower self-reported recovery, re-sprain within 3 months, MRI
      determined number of sprained ligaments, severity and bone bruise were found to
      be independent predictors of poor recovery. Age was one prognostic factor that
      demonstrated a consistent association with outcome in three studies, however
      cautious interpretation is advised. CONCLUSIONS: The associations between
      prognostic factors and poor recovery after an acute lateral ankle sprain are
      largely inconclusive. At present, there is insufficient evidence to recommend any
      factor as an independent predictor of outcome. There is a need for well-conducted
      prospective cohort studies with adequate sample size and long-term follow-up to
      provide robust evidence on prognostic factors of recovery following an acute
      lateral ankle sprain. TRIAL REGISTRATION: Prospero registration: CRD42014014471.

PMID- 29061136
TI  - Isolation and characterization of three new anti-proliferative Sesquiterpenes
      from Polygonum barbatum and their mechanism via apoptotic pathway.
AB  - BACKGROUND: The emergence of chemoresistant cancers and toxicity related to
      existing chemotherapeutic agents, demand the search for new pharmacophore with
      enhanced anti-cancer activity and least toxicity. For this purpose, three new
      sesquiterpenes were isolated from ethyl acetate fraction of the aerial parts of
      the plant Polygonum barbatum and evaluated for their anti-cancer potential.
      METHODS: The structural elucidation and characterization of the isolated
      compounds 1-3 were performed using various spectroscopic techniques such as mass,
      UV, IR, and extensive 1D/2D-NMR spectroscopy. Furthermore, the compounds 1-3 were
      subjected to screening of anti-cancer activity against different cell lines
      followed by brief analysis of apoptotic and anti-angiogenic potentials of the
      potent hit against non-small cell lung carcinoma cell line. RESULTS: All the
      compounds 1-3 were subjected to anti-proliferative potential against non-small
      cell lung carcinoma (NCI-H460), breast cancer (MCF-7), cervical cancer (HeLa) and
      normal mouse fibroblast (NIH-3 T3) cell lines. Among these, compound 3 was found
      to be more cytotoxic against NCI-H460 and MCF-7 cells (IC50 = 17.86 +/- 0.72 and
      11.86 +/- 0.46 MUM respectively). When compared with the standard drug cisplatin
      compound 3 was found to have more potent activity against NCI-H460 (IC50 = 19 +/-
      1.24 MUM) as compared to MCF-7 cell lines (IC50 = 9.62 +/- 0.5 MUM). Compound 3
      induced apoptosis in NCI-H460 cells in a dose dependent manner. It significantly
      downregulated, the expression of anti-apoptotic (BCL-2 L1 and p53) and increased
      the expression of pro-apoptotic (BAK and BAX) genes. Besides apoptosis, it also
      significantly reduced the cell migration and downregulated the angiogenic genes
      (i.e. VEGF and COX-2), thereby, inhibiting angiogenesis in NCI-H460 cells.
      CONCLUSION: Compound 3 possesses potent anti-proliferative potential as well as
      induced apoptosis and inhibited the cell migration of the cancerous cells by
      altering the gene expression, responsible for it.

PMID- 29061137
TI  - Performance of Leishmania PFR1 recombinant antigen in serological diagnosis of
      asymptomatic canine leishmaniosis by ELISA.
AB  - BACKGROUND: Leishmania infantum is a protozoan parasite transmitted by
      phlebotomine sand flies that causes life-threatening disease in humans and dogs.
      The dog is the primary reservoir of the parasite and early diagnosis of canine
      leishmaniosis is crucial at the clinical and epidemiological level. The currently
      available serological tests for CanL diagnostic show limitations therefore the
      aim of the present study was to investigate the diagnostic performance of an
      indirect antibody ELISA based on the Leishmania infantum recombinant antigen PFR1
      in asymptomatically infected dogs. One hundred fifty-six dogs including
      Leishmania-free experimental Beagles and pet dogs from England, Scotland and
      Leishmania-endemic Murcia in Spain, were tested with the assay. The later were
      also tested with two commercial L. infantum crude antigen ELISAs (INgezim and
      Civtest, respectively) and a real-time kinetoplast PCR test. RESULTS: Anti-PFR1
      antibodies were detected in the four groups of dogs, and the mean log-transformed
      optical density (OD) values were lowest in Beagles and in dogs from England and
      highest among dogs from Murcia (p < 0.05). Using the highest OD in beagles as the
      PFR1 ELISA cut-off point, the estimated seroprevalence was 27% (14-40%) in dogs
      from Murcia, 4% (0-9%) in dogs from Scotland and 3% (0-8%) in dogs from England
      (p < 0.05). Seroprevalence in dogs from Murcia according to the INgezim and
      Civtest ELISAs were 24% (12-37%) and 31% (18-45%), respectively, whilst the
      prevalence of infection based on PCR in these dogs was 73% (60-86). The
      percentages of PFR1-positive dogs that tested negative on the INgezim and Civtest
      ELISAs were 30% and 35%, respectively, and all of them tested positive on the PCR
      test. Relative to the PCR, the specificity, sensitivity and area under the ROC
      curve of the PFR1 ELISA were 100%, 36% and 0.74 (0.63-0.86), respectively.
      CONCLUSIONS: The ability shown by the PFR1 ELISA to detect infected dogs that go
      undetected by the crude antigen ELISAs is clinically and epidemiologically useful
      and PFR1 could be considered a candidate for a multi-antigen-based immunoassay
      for early detection of L. infantum infected dogs.

PMID- 29061139
TI  - Evaluation of lymphatic vessel dilatations by anterior segment swept-source
      optical coherence tomography: case report.
AB  - BACKGROUND: Conjunctival lymphangiectasia is a rare condition presumably caused
      by the obstruction of lymphatic channels or by an abnormal connection between
      conjunctival lymphatic and blood vessels. Diagnosis is based on clinical
      appearance and histology. We report a case of conjunctival lymphangiectasia in
      which anterior segment optical coherence tomography (OCT) was used to assist the
      diagnosis and the planning of the biopsy location. CASE PRESENTATION: A 31-year
      old woman was referred with repeated episodes of conjunctival "hemorrhages" and
      chemosis with extended recovery periods over the last months. Other symptoms were
      dryness, redness, burning sensation and itching. Photo documentation, anterior
      segment OCT, ultrasound, computer tomography (CT) and magnetic resonance imaging
      (MRI) of the brain were performed. MRI revealed dilated atypical Virchow-Robin
      space (VRS). Conjunctival biopsy was taken and the location of the biopsy was
      selected based on OCT findings. Based on the clinical appearance we suspected the
      case to be conjunctival lymphangiectasia or lymphangioma. Histology and
      immunhistochemistry confirmed the diagnosis of conjunctival lymphangiectasia.
      CONCLUSIONS: Anterior segment OCT is a non-invasive tool, useful in the
      evaluation of conjunctival lesions and planning surgery.

PMID- 29061140
TI  - Barriers and facilitators to the implementation of a school-based physical
      activity policy in Canada: application of the theoretical domains framework.
AB  - BACKGROUND: In British Columbia Canada, a Daily Physical Activity (DPA) policy
      was mandated that requires elementary school teachers to provide students with
      opportunities to achieve 30 min of physical activity during the school day.
      However, the implementation of school-based physical activity policies is
      influenced by many factors. A theoretical examination of the factors that impede
      and enhance teachers' implementation of physical activity policies is necessary
      in order to develop strategies to improve policy practice and achieve desired
      outcomes. This study used the Theoretical Domains Framework (TDF) to understand
      teachers' barriers and facilitators to the implementation of the DPA policy in
      one school district. Additionally, barriers and facilitators were examined and
      compared according to how the teacher implemented the DPA policy during the
      instructional school day. METHODS: Interviews were conducted with thirteen
      teachers and transcribed verbatim. One researcher performed barrier and
      facilitator extraction, with double extraction occurring across a third of the
      interview transcripts by a second researcher. A deductive and inductive
      analytical approach in a two-stage process was employed whereby barriers and
      facilitators were deductively coded using TDF domains (content analysis) and
      analyzed for sub-themes within each domain. Two researchers performed coding.
      RESULTS: A total of 832 items were extracted from the interview transcripts. Some
      items were coded into multiple TDF domains, resulting in a total of 1422
      observations. The most commonly coded TDF domains accounting for 75% of the total
      were Environmental context and resources (ECR; n = 250), Beliefs about
      consequences (n = 225), Social influences (n = 193), Knowledge (n = 100), and
      Intentions (n = 88). Teachers who implemented DPA during instructional time
      differed from those who relied on non-instructional time in relation to Goals,
      Behavioural regulation, Social/professional role and identity, Beliefs about
      Consequences. Forty-one qualitative sub-themes were identified across the
      fourteen domains and exemplary quotes were highlighted. CONCLUSIONS: Teachers
      identified barriers and facilitators relating to all TDF domains, with ECR,
      Beliefs about consequences, Social influences, Knowledge and Intentions being the
      most often discussed influencers of DPA policy implementation. Use of the TDF to
      understand the implementation factors can assist with the systematic development
      of future interventions to improve implementation.

PMID- 29061138
TI  - The evidence base for circulating tumour DNA blood-based biomarkers for the early
      detection of cancer: a systematic mapping review.
AB  - BACKGROUND: The presence of circulating cell-free DNA from tumours in blood
      (ctDNA) is of major importance to those interested in early cancer detection, as
      well as to those wishing to monitor tumour progression or diagnose the presence
      of activating mutations to guide treatment. In 2014, the UK Early Cancer
      Detection Consortium undertook a systematic mapping review of the literature to
      identify blood-based biomarkers with potential for the development of a non
      invasive blood test for cancer screening, and which identified this as a major
      area of interest. This review builds on the mapping review to expand the ctDNA
      dataset to examine the best options for the detection of multiple cancer types.
      METHODS: The original mapping review was based on comprehensive searches of the
      electronic databases Medline, Embase, CINAHL, the Cochrane library, and Biosis to
      obtain relevant literature on blood-based biomarkers for cancer detection in
      humans (PROSPERO no. CRD42014010827). The abstracts for each paper were reviewed
      to determine whether validation data were reported, and then examined in full.
      Publications concentrating on monitoring of disease burden or mutations were
      excluded. RESULTS: The search identified 94 ctDNA studies meeting the criteria
      for review. All but 5 studies examined one cancer type, with breast, colorectal
      and lung cancers representing 60% of studies. The size and design of the studies
      varied widely. Controls were included in 77% of publications. The largest study
      included 640 patients, but the median study size was 65 cases and 35 controls,
      and the bulk of studies (71%) included less than 100 patients. Studies either
      estimated cfDNA levels non-specifically or tested for cancer-specific mutations
      or methylation changes (the majority using PCR-based methods). CONCLUSION: We
      have systematically reviewed ctDNA blood biomarkers for the early detection of
      cancer. Pre-analytical, analytical, and post-analytical considerations were
      identified which need to be addressed before such biomarkers enter clinical
      practice. The value of small studies with no comparison between methods, or even
      the inclusion of controls is highly questionable, and larger validation studies
      will be required before such methods can be considered for early cancer
      detection.

PMID- 29061141
TI  - A multi-stakeholder evaluation of the Baltimore City virtual supermarket program.
AB  - BACKGROUND: Increasing access to healthy foods and beverages in disadvantaged
      communities is a public health priority due to alarmingly high rates of obesity.
      The Virtual Supermarket Program (VSP) is a Baltimore City Health Department
      program that uses online grocery ordering to deliver food to low-income
      neighborhoods. This study evaluates stakeholder preferences and barriers of
      program implementation. METHODS: This study assessed the feasibility,
      sustainability and efficacy of the VSP by surveying 93 customers and interviewing
      14 programmatic stakeholders who had recently used the VSP or been involved with
      program design and implementation. RESULTS: We identified the following themes:
      The VSP addressed transportation barriers and food availability. The VSP impacted
      customers and the city by including improving food purchasing behavior, creating
      a food justice "brand for the city", and fostering a sense of community.
      Customers appreciated using Supplemental Nutrition Assistance Program (SNAP)
      benefits to pay for groceries, but policy changes are needed allow online
      processing of SNAP benefits. CONCLUSIONS: This evaluation summarizes lessons
      learned and serves as a guide to other public health leaders interested in
      developing similar programs. Provisions in the U.S. Department of Agriculture
      (USDA) Farm Bill 2014 allow for select grocers to pilot online transactions with
      SNAP benefits. If these pilots are efficacious, the VSP model could be easily
      disseminated.

PMID- 29061142
TI  - Systematic identification of regulatory variants associated with cancer risk.
AB  - BACKGROUND: Most cancer risk-associated single nucleotide polymorphisms (SNPs)
      identified by genome-wide association studies (GWAS) are noncoding and it is
      challenging to assess their functional impacts. To systematically identify the
      SNPs that affect gene expression by modulating activities of distal regulatory
      elements, we adapt the self-transcribing active regulatory region sequencing
      (STARR-seq) strategy, a high-throughput technique to functionally quantify
      enhancer activities. RESULTS: From 10,673 SNPs linked with 996 cancer risk
      associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the
      fragments that positively regulate gene expression, and 758 SNPs in the fragments
      with negative regulatory activities. Among them, 70 variants are regulatory
      variants for which the two alleles confer different regulatory activities. We
      analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and
      leukemia risk-associated SNP rs12142375-and demonstrate their endogenous
      regulatory activities on expression of ATF7IP and PDE4B genes, respectively,
      using a CRISPR-Cas9 approach. CONCLUSIONS: By identifying regulatory variants
      associated with cancer susceptibility and studying their molecular functions, we
      hope to help the interpretation of GWAS results and provide improved information
      for cancer risk assessment.

PMID- 29061144
TI  - An evaluation of transport mode shift policies on transport-related physical
      activity through simulations based on random forests.
AB  - BACKGROUND: Physical inactivity is widely recognized as one of the leading causes
      of mortality, and transport accounts for a large part of people's daily physical
      activity. This study develops a simulation approach to evaluate the impact of the
      Ile-de-France Urban Mobility Plan (2010-2020) on physical activity, under the
      hypothesis that the intended transport mode shifts are realized. METHODS: Based
      on the Global Transport Survey (2010, n = 21,332) and on the RECORD GPS Study
      (2012-2013, n = 229) from the French capital region of Paris (Ile-de-France), a
      simulation method was designed and tested. The simulation method used
      accelerometer data and random forest models to predict the impact of the
      transport mode shifts anticipated in the Mobility Plan on transport-related
      moderate-to-vigorous physical activity (T-MVPA). The transport mode shifts
      include less private motorized trips in favor of more public transport, walking,
      and biking trips. RESULTS: The simulation model indicated a mean predicted
      increase of 2 min per day of T-MVPA, in case the intended transport mode shifts
      in the Ile-de-France Urban Mobility Plan were realized. The positive effect of
      the transport mode shifts on T-MVPA would, however, be larger for people with a
      higher level of education. This heterogeneity in the positive effect would
      further increase the existing inequality in transport-related physical activity
      by educational level. CONCLUSIONS: The method presented in this paper showed a
      significant increase in transport-related physical activity in case the intended
      mode shifts in the Ile-de-France Urban Mobility Plan were realized. This
      simulation method could be applied on other important health outcomes, such as
      exposure to noise or air pollution, making it a useful tool to anticipate the
      health impact of transport interventions or policies.

PMID- 29061146
TI  - Health-related quality of life in persons with West Nile virus infection: a
      longitudinal cohort study.
AB  - BACKGROUND: West Nile virus (WNV) infections are predominantly asymptomatic,
      although almost 1% become neuroinvasive and debilitating. We describe the impact
      of neuroinvasive and non-neuroinvasive disease on patient health-related quality
      of life (HRQoL). METHODS: Short Form 36 questionnaire data came from a Canadian
      WNV cohort (Loeb 2008) of 154 patients followed for up to three years. We
      generated health utilities using the SF-6D. We calculated mean utility scores
      throughout follow-up and examined predictors using a linear mixed-effects model.
      We summarized HRQoL post-acute infection as: (i) long-term utility (mean of
      scores one year onward); (ii) area under the curve (AUC) one year onward. We
      examined predictors using beta regression. We used multiple imputation for
      sensitivity analysis. RESULTS: Mean utility scores improved from 0.59 (95% CI:
      0.38, 0.93) at baseline to 0.77 (0.53, 1) at six months, before plateauing for
      the remaining two years. Mean long-term utility was 0.81 (0.78, 0.85) and mean
      AUC was 0.80 (0.76, 0.84). Patients with neuroinvasive disease had consistently
      worse scores than their non-neuroinvasive counterparts, with the gap nearly
      closed after six months. After adjusting for confounding, neuroinvasive disease
      was not a significant predictor of HRQoL either throughout follow-up or post
      acute infection. Rather, number of comorbidities and baseline utility scores
      were. Sensitivity analysis showed similar findings. CONCLUSIONS: Patients with
      WNV infection reported low HRQoL during acute illness, but improved rapidly by
      six months, regardless of neuroinvasive disease status. This is the first study
      reporting health utilities for WNV infection.

PMID- 29061147
TI  - Correction to: the disruption of mitochondrial axonal transport is an early event
      in neuroinflammation.

PMID- 29061143
TI  - Epitranscriptomic influences on development and disease.
AB  - RNA contains over 150 types of chemical modifications. Although many of these
      chemical modifications were discovered several decades ago, their functions were
      not immediately apparent. Discoveries of RNA demethylases, along with advances in
      mass spectrometry and high-throughput sequencing techniques, have caused research
      into RNA modifications to progress at an accelerated rate. Post-transcriptional
      RNA modifications make up an epitranscriptome that extensively regulates gene
      expression and biological processes. Here, we present an overview of recent
      advances in the field that are shaping our understanding of chemical
      modifications, their impact on development and disease, and the dynamic
      mechanisms through which they regulate gene expression.

PMID- 29061145
TI  - Effects of home-based long-term care services on caregiver health according to
      age.
AB  - BACKGROUND: Caregiver health is a crucial public health concern due to the
      increasing number of elderly people with disabilities. Elderly caregivers are
      more likely to have poorer health and be a care recipient than younger
      caregivers. The Taiwan government offers home-based long-term care (LTC) services
      to provide formal care and decrease the burden of caregivers. This study examined
      the effects of home-based LTC services on caregiver health according to caregiver
      age. METHODS: This cross-sectional study included a simple random sample of care
      recipients and their caregivers. The care recipients had used LTC services under
      the Ten-Year Long-Term Care Project (TLTCP) in Taiwan. Data were collected
      through self-administered questionnaires from September 2012 to January 2013. The
      following variables were assessed for caregivers: health, sex, marital status,
      education level, relationship with care recipient, quality of relationship with
      care recipient, job, household monthly income, family income spent on caring for
      the care recipient (%) and caregiving period. Furthermore, the following factors
      were assessed for care recipients: age, sex, marital status, education level,
      living alone, number of family members living with the care recipient, quality of
      relationship with family and dependency level. The health of the caregivers and
      care recipients was measured using a self-rated question (self-rated health [SRH]
      was rated as very poor, poor, fair, good and very good). RESULTS: The study
      revealed that home nursing care was significantly associated with the health of
      caregivers aged 65 years or older; however, caregivers aged less than 65 who had
      used home nursing care, rehabilitation or respite care had poorer health than
      those who had not used these services. In addition, the following variables
      significantly improved the health of caregivers aged 65 years or older: caregiver
      employment, 20% or less of family income spent on caregiving than 81%-100% and
      higher care recipient health. The involvement of daughters-in-law, rather than
      spouses, and care recipient health were positively related to the health of
      caregivers aged less than 65 years. CONCLUSIONS: The findings suggest that home
      based LTC service use benefits the health of elderly caregivers. By contrast,
      home-based LTC service use may be negatively correlated with the health of the
      caregivers aged less than 65 years.

PMID- 29061148
TI  - Integrated community case management by drug sellers influences appropriate
      treatment of paediatric febrile illness in South Western Uganda: a quasi
      experimental study.
AB  - BACKGROUND: Fever case management is a major challenge for improved child health
      globally, despite existence of cheap and effective child survival health
      technologies. The integrated Community Case Management (iCCM) intervention of
      paediatric febrile illnesses though adopted by Uganda's Ministry of Health to be
      implemented by community health workers, has not addressed the inaccess to life
      saving medicines and diagnostics. Therefore, the iCCM intervention was
      implemented in private drug shops and evaluated for its effect on appropriate
      treatment of paediatric fever in a low malaria transmission setting in South
      Western Uganda. METHODS: From June 2013 to September 2015, the effect of the iCCM
      intervention on drug seller paediatric fever management and adherence to iCCM
      guidelines was assessed in a quasi-experimental study in South Western Uganda. A
      total of 212 care-seeker exit interviews were done before and 285 after in the
      intervention arm as compared to 216 before and 268 care-seeker interviews at the
      end of the study period in the comparison arm. The intervention effect was
      assessed by difference-in-difference analysis of drug seller treatment practices
      against national treatment recommendations between the intervention and
      comparison arms. Observed proportions among care-seeker interviews were compared
      with corresponding proportions from 5795 child visits recorded in patient
      registries and 49 direct observations of drug seller-care-seeker encounters in
      intervention drug shops. RESULTS: The iCCM intervention increased the appropriate
      treatment of uncomplicated malaria, pneumonia symptoms and non-bloody diarrhoea
      by 80.2% (95% CI 53.2-107.2), 65.5% (95% CI 51.6-79.4) and 31.4% (95% CI 1.6
      61.2), respectively. Within the intervention arm, drug seller scores on
      appropriate treatment for pneumonia symptoms and diagnostic test use were the
      same among care-seeker exit interviews and direct observation. A linear trend
      (negative slope, - 0.009 p value < 0.001) was observed for proportions of child
      cases prescribed any antimicrobial medicine in the intervention arm drug shops.
      CONCLUSIONS: The iCCM intervention improved appropriate treatment for
      uncomplicated malaria, pneumonia symptoms and diarrhoea. Drug seller adherence to
      iCCM guidelines was high, without causing excessive prescription of antimicrobial
      medicines in this study. Further research should assess whether this effect is
      sustained over time and under routine supervision models.

PMID- 29061149
TI  - A modified and tailored human follicle isolation procedure improves follicle
      recovery and survival.
AB  - BACKGROUND: Ovarian tissue cryopreservation followed by transplantation after
      cancer remission is the most commonly applied fertility restoration approach in
      very young girls and women who require immediate cancer therapy. However,
      clinicians strongly advise against reimplantation of one's own ovarian tissue
      when there is a high risk of recurrence after grafting. For these patients,
      development of an alternative strategy, namely a transplantable artificial ovary,
      offers future hope of conceiving. The first essential requirement for an
      artificial ovary is the set-up of a safe and effective follicle isolation
      procedure. Despite encouraging results with different variants of this technique,
      none of them take into the account the physiology and great variability in
      follicular density inside individual tissue fragments and between different
      patients. The goal of this study was to improve our previously applied follicle
      isolation procedure in order to develop a tailored isolation procedure for human
      follicles according to individual tissue properties. To this end, enzymatic
      digestion was divided into three time intervals in order to initially recover the
      first follicles to be isolated, and then further dissociate undigested fragments
      of tissue containing entrapped follicles. RESULTS: After thawing frozen human
      ovarian tissue using a modified and tailored follicle isolation method, already
      35% of follicles were fully isolated and recovered after 30 min of enzymatic
      digestion. Indeed, this protocol resulted in a higher follicle yield (p < 0.01)
      and greater numbers of primordial and primary follicles (p < 0.05) than the
      previous approach. However, no significant difference was found in caspase-3
      positive and Ki67-positive staining between the two isolation protocols. In
      addition, greater follicle quality was demonstrated. When human follicles
      isolated using the modified protocol were encapsulated in a fibrin matrix with
      high concentrations of fibrinogen and thrombin and xenografted to a SCID mouse,
      more follicles were found to be healthy after one week of transplantation than in
      a previous our study. CONCLUSIONS: With the modified follicle isolation method,
      we were able to maximize the number and quality of isolated primordial and
      primary follicles, and develop a tailored follicle isolation procedure according
      to individual tissue properties. Moreover, improved follicle survival inside an
      artificial ovary prototype was detected after one week of xenografting.

PMID- 29061150
TI  - Dysregulated long noncoding RNAs (lncRNAs) in hepatocellular carcinoma:
      implications for tumorigenesis, disease progression, and liver cancer stem cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with a
      poor prognosis worldwide. While early stage tumours can be treated with curative
      approaches such as liver transplantation or surgical resection, these are only
      suitable for a minority of patients. Those with advanced stage disease are only
      suitable for supportive approaches and most are resistant to the conventional
      chemotherapy or radiotherapy. Liver cancer stem cells (LCSCs) are a small subset
      of cancer cells with unlimited differentiation ability and tumour forming
      potential. In order to develop novel therapeutic approaches for HCC, we need to
      understand how the cancer develops and why treatment resistance occurs. Using
      high-throughput sequencing techniques, a large number of dysregulated long
      noncoding RNAs (lncRNAs) have been identified, and some of which are closely
      linked to key aspects of liver cancer pathology, progression, outcomes and for
      the maintenance of cancer stem cell-like properties. In addition, some lncRNAs
      are potential biomarkers for HCC diagnosis and may serve as the therapeutic
      targets. This review summarizes data recently reported lncRNAs that might be
      critical for the maintenance of the biological properties of LCSCs.

PMID- 29061151
TI  - Comparison of health-related quality of life among men with different co-existing
      severe mental disorders in treatment for substance use.
AB  - BACKGROUND: Patient-perceived health-related quality of life has become an
      important outcome in health care as an indicator of treatment effectiveness and
      recovery for patients with substance use disorder. As no study has assessed
      health-related quality of life among male patients with substance use disorder
      and co-existing severe mental illness, we compared health-related quality of life
      among patients with substance use disorder and the following severe mental
      illness diagnosis in Barcelona, Spain: schizophrenia, bipolar disorder, major
      depressive disorder, and examined the associations with clinically related
      variables. Additionally, we compared results for health-related quality of life
      in patients with substance use disorder and severe mental illness, with Spanish
      population norms. METHODS: We assessed 107 substance use disorder male patients
      using the 36-Item Short Form Health Survey comparing results across three groups
      with: comorbid schizophrenia (n = 37), comorbid bipolar disorder (n = 34), and
      comorbid major depressive disorder (n = 36). Multiple analyses of variance were
      performed to explore health-related quality of life by the type of co-existing
      SMI and linear regression analyses examined clinical correlates for the 36-Item
      Short Form Health Survey dimensions for each group. RESULTS: There were
      differences in Physical Functioning, Vitality and the Physical Composite Scale
      among groups. Poorer Physical Functioning was observed for patients with comorbid
      schizophrenia (80.13+/-3.27) and major depressive disorder (81.97+/-3.11)
      compared with comorbid bipolar disorder patients (94.26+/-1.93). Patients with
      substance use disorder and schizophrenia presented lower scores in Vitality
      (41.6+/-2.80) than those with co-existing bipolar disorder (55.68+/-3.66) and
      major depressive disorder (53.63+/-2.92). Finally, results in the Physical
      Composite Scale showed lower scores for patients with comorbid schizophrenia
      (51.06+/-1.41) and major depressive disorder (51.99+/-1.87) than for those with
      bipolar disorder (60.40+/-2.17). Moreover, all groups had poorer health-related
      quality of life, especially Social Functioning, Role-Emotional and Mental Health,
      compared with population norms. Different clinical variables (e.g. medical
      disease comorbidity, severity of addiction, psychiatric symptomatology, suicide
      attempts, drug relapses) were related to different health-related quality of life
      dimensions depending on the co-existing severe mental illness. CONCLUSIONS: Among
      male patients with substance use disorder, co-existing severe mental illness may
      influence some health-related quality of life dimensions and clinically related
      variables. Such differences may require tailored therapeutic interventions.

PMID- 29061153
TI  - Randomized trial comparing group size of periodic in-person sessions in a
      remotely delivered weight loss intervention.
AB  - BACKGROUND: Few randomized studies have examined differential effects of group
      size in behavioral weight control, especially in hybrid programs that include
      Internet treatment approaches. METHODS: Randomized controlled trial (n = 195)
      comparing a 4 month hybrid internet weight loss program coupled with monthly face
      to face groups of 100 persons (Large Group, LG; 1 group) or to the same approach
      with monthly groups of 20 persons (Small Group, SG; 4 groups). Repeated-measures
      mixed-model analysis with age and race as covariates were used to estimate
      primary (weight) and secondary outcomes, and to test group differences in change
      over time. RESULTS: The sample was 46.3 years old +/-10.4, 90.3% female, and
      51.9% non-white, with BMI 37.9 +/- 8.4 kg/m2. Participants in the LG were more
      likely to return for the 4-month assessment visit than those in the SG (p =
      0.04). Participants randomized to both the LG and SG conditions experienced
      significant WL over time (no between group difference: -4.1 kg and -3.7 kg,
      respectively) and weight loss was positively associated with attendance at
      monthly meetings and logins to the website. Satisfaction with the program was
      high and similar in both groups (94.4% reported that they were "satisfied" or
      "very satisfied"). CONCLUSIONS: Using a hybrid approach of in-person and online
      weight loss interventions may be an effective way to reach larger and more
      diverse populations. Delivering the face to face component of the intervention in
      groups larger than those traditionally delivered (20-25 people) could increase
      the cost-effectiveness of group-based behavioral weight loss interventions.
      CLINICAL TRIALS REGISTRATION NUMBER: NCT01615471 . Registered June 6, 2012.
      Registered retrospectively.

PMID- 29061152
TI  - Individualized perfusion targets in hypoxic ischemic brain injury after cardiac
      arrest.
AB  - Secondary injury is a major determinant of outcome in hypoxic ischemic brain
      injury (HIBI) after cardiac arrest and may be mitigated by optimizing cerebral
      oxygen delivery (CDO2). CDO2 is determined by cerebral blood flow (CBF), which is
      dependent upon mean arterial pressure (MAP). In health, CBF remains constant over
      the MAP range through cerebral autoregulation. In HIBI, the zone of intact
      cerebral autoregulation is narrowed and varies for each patient. Maintaining MAP
      within the intact autoregulation zone may mitigate ischemia, hyperemia and
      secondary injury. The optimal MAP in individual patients can be determined using
      real time autoregulation monitoring techniques.

PMID- 29061154
TI  - A multi-centre randomised trial to compare the effectiveness of geriatrician-led
      admission avoidance hospital at home versus inpatient admission.
AB  - BACKGROUND: There is concern that existing models of acute hospital care will
      become unworkable as the health service admits an increasing number of frail
      older people with complex health needs, and that there is inadequate evidence to
      guide the planning of acute hospital level services. We aim to evaluate whether
      geriatrician-led admission avoidance to hospital at home is an effective
      alternative to hospital admission. METHODS/DESIGN: We are conducting a multi-site
      randomised open trial of geriatrician-led admission avoidance hospital at home,
      compared with admission to hospital. We are recruiting older people with markers
      of frailty or prior dependence who have been referred to admission avoidance
      hospital at home for an acute medical event. This includes patients presenting
      with delirium, functional decline, dependence, falls, immobility or a background
      of dementia presenting with physical disease. Participants are randomised using a
      computerised random number generator to geriatrician-led admission avoidance
      hospital at home or a control group of inpatient admission in a 2:1 ratio in
      favour of the intervention. The primary endpoint 'living at home' (the inverse of
      death or living in a residential care setting) is measured at 6 months follow-up,
      and we also collect data on this outcome at 12 months. Secondary outcomes include
      the incidence of delirium, mortality, new long-term residential care, cognitive
      impairment, activities of daily living, quality of life and quality-adjusted
      survival, length of stay, readmission or transfer to hospital. We will conduct a
      parallel economic evaluation, and a process evaluation that includes an interview
      study to explore the experiences of patients and carers. DISCUSSION: Health
      systems around the world are examining how to provide acute hospital-level care
      to older adults in greater numbers with a fixed or shrinking hospital resource.
      This trial is the first large multi-site randomised trial of geriatrician-led
      admission avoidance hospital at home, and will provide evidence on alternative
      models of healthcare for older people who require hospital admission. TRIAL
      REGISTRATION: ISRCTN60477865 : Registered on 10 March 2014. Trial Sponsor:
      University of Oxford. Version 3.1, 14/06/2016.

PMID- 29061157
TI  - Promoting RNA editing by ADAR attraction.
AB  - Concentration is important and not only while driving; a new study indicates how
      an adjacent genomic element helps to increase the efficiency of a specific
      adenosine to inosine RNA editing reaction, by providing a means to increase the
      local concentration of the RNA editing enzyme ADAR.

PMID- 29061155
TI  - Building capacity for medical education research in family medicine: the Program
      for Innovation in Medical Education (PIME).
AB  - BACKGROUND: Despite the apparent benefits to teaching, many faculty members are
      reluctant to participate in medical education research (MER) for a variety of
      reasons. In addition to the further demand on their time, physicians often lack
      the confidence to initiate MER projects and require more support in the form of
      funding, structure and guidance. These obstacles have contributed to a decline in
      physician participation in MER as well as to a perceived decay in its quality. As
      a countermeasure to encourage physicians to undertake research, the Department of
      Family Medicine at the University of Ottawa implemented a programme in which
      physicians receive the funding, coaching and support staff necessary to complete
      a 2-year research project. The programme is intended primarily for first-time
      researchers and is meant to serve as a gateway to a research career funded by
      external grants. Since its inception in 2010, the Program for Innovation in
      Medical Education (PIME) has supported 16 new clinician investigators across 14
      projects. METHODS: We performed a programme evaluation 3 years after the
      programme launched to assess its utility to participants. This evaluation
      employed semi-structured interviews with physicians who performed a research
      project within the programme. RESULTS: Programme participants stated that their
      confidence in conducting research had improved and that they felt well supported
      throughout their project. They appreciated the collaborative nature of the
      programme and remarked that it had improved their willingness to solicit the
      expertise of others. Finally, the programme allowed participants to develop in
      the scholarly role expected by family physicians in Canada. CONCLUSION: The PIME
      may serve as a helpful model for institutions seeking to engage faculty
      physicians in Medical Education Research and to thereby enhance the teaching
      received by their medical learners.

PMID- 29061158
TI  - Correction to: Influence of tumor extent on central lymph node metastasis in
      solitary papillary thyroid microcarcinomas: a retrospective study of 1092
      patients.

PMID- 29061156
TI  - Porcine Viperin protein inhibits the replication of classical swine fever virus
      (CSFV) in vitro.
AB  - BACKGROUND: Classical swine fever virus (CSFV) is the causative pathogen of
      Classical swine fever (CSF), a highly contagious disease of swine. Viperin is one
      of the hundreds of interferon-stimulated genes (ISGs), and possesses a wide range
      of antiviral activities. The aim of this study was to explore whether porcine
      Viperin has the anti-CSFV activity. METHOD: The influences of CSFV infection on
      Viperin expression and Newcastle disease virus (NDV)/Pseudorabies virus (PRV)
      induced Viperin expression were examined in 3D4/21 cells and porcine peripheral
      blood mononuclear cells (PBMCs). Porcine Viperin gene was amplified to generate
      cell line PK-Vi over-expressing Viperin. CSFV was inoculated in the cell lines
      and viral load was detected by qRT-PCR, virus titration and Western blot. The
      influence of Viperin expression on CSFV binding, entry and release in the cells
      was also examined. The co-localization of Viperin with CSFV and its proteins (E2,
      NS5B) was determined by confocal laser scanning microscopy test. Co-IP assay was
      performed to check the interaction of Viperin with CSFV proteins. RESULTS: CSFV
      infection could not induce Viperin expression in vitro while significantly
      inhibiting NDV/PRV-induced Viperin expression at 12, 24 and 48 h post infection
      (hpi; P < 0.05). The proliferation of CSFV in PK-Vi was significantly inhibited
      at 24, 48 and 72 hpi (P < 0.05), comparing with control cells (PK-C1 expressing
      EGFP). Virus in both cell culture supernatants and cell pellets were reduced
      equally. CSFV binding and entry in the cells were not interfered by Viperin
      expression. These results indicated its anti-CSFV function occurred during the
      genome and/or protein synthesis step. Confocal laser scanning microscopy test
      showed the Viperin-EGFP protein co-localized with CSFV E2 protein in CSFV
      infected PK-Vi cells. Further experiments indicated that Viperin protein co
      localized with E2 and NS5B proteins of CSFV in the transfected 293 T cells.
      Furthermore, Co-IP assay confirmed the interaction of Viperin with E2 protein,
      but not NS5B. CONCLUSION: Porcine Viperin effectively inhibited CSFV replication
      in vitro, potentially via the interaction of Viperin with CSFV E2 protein in
      cytoplasm. The results provided foundation for further studies of the interaction
      of Viperin with CSFV and other viruses.

PMID- 29061159
TI  - Genetic polymorphisms of HLA-DP and isolated anti-HBc are important subsets of
      occult hepatitis B infection in Indonesian blood donors: a case-control study.
AB  - BACKGROUND: Occult hepatitis B infection (OBI) is defined as the presence of
      hepatitis B virus (HBV) DNA in the serum and/or liver in HBsAg-negative
      individuals. OBI is associated with the risk of viral transmission, especially in
      developing countries, and with progressive liver disease and reactivation in
      immunosuppressive patients. The objective of this study was to evaluate the
      relation of OBI to HLA-DP single nucleotide polymorphisms (SNPs) encoding antigen
      binding sites for the immune response to HBV infection. As HLA-DP variants affect
      the mRNA expression of HLA-DPA1 and HLA-DPB1 in the liver, we hypothesised that
      high levels of HLA-DPA1 and HLA-DPB1 expression favour OBI development. METHODS:
      The study enrolled 456 Indonesian healthy blood donors (HBsAg negative). OBI was
      defined as the presence of HBV-DNA in at least two of four open reading frames
      (ORFs) of the HBV genome detected by nested PCR. SNPs in HLA-DPA1 (rs3077) and
      HLA-DPB1 (rs3135021, rs9277535, and rs2281388) were genotyped using real-time
      Taqman(r) genotyping assays. RESULTS: Of 122 samples positive for anti-HBs and/or
      anti-HBc, 17 were determined as OBI. The minor allele in rs3077 was significantly
      correlated with OBI [odds ratio (OR) = 3.87, 95% confidence interval (CI) = 1.58
      9.49, p = 0.0015]. The prevalence of the minor allele (T) was significantly
      higher in subjects with OBI than in those without (59% and 33%, respectively).
      The combination of haplotype markers (TGA for rs3077-rs3135021-rs9277535) was
      associated with increased risk of OBI (OR = 4.90, 95%CI = 1.12-21.52 p = 0.038).
      The prevalence of OBI was highest in the isolated anti-HBc group among the three
      seropositive categories: anti-HBs <500 mIU/ml, anti-HBs >=500 mIU/ml, and
      isolated anti-HBc (29.41%, p = 0.014). CONCLUSION: Genetic variants of HLA-DP and
      the presence of anti-HBc are important predictors of OBI in Indonesian blood
      donors. TRIAL REGISTRATION: Ref: KE/FK/194/EC; registered 01 March 2013.
      Continuing approval Ref: KE/FK/536/EC; registered 12 May 2014.

PMID- 29061160
TI  - Molecular prevalence of trypanosome infections in cattle and tsetse flies in the
      Maasai Steppe, northern Tanzania.
AB  - BACKGROUND: African trypanosomosis is a disease of public health and economic
      importance that poses a major threat to the livelihoods of people living in the
      Maasai Steppe, where there is a significant interaction between people, livestock
      and wildlife. The vulnerability of the Maasai people to the disease is enhanced
      by the interaction of their cattle, which act as vehicles for trypanosomes, and
      tsetse flies close to wildlife in protected areas. This study was aimed at
      identification of trypanosome infections circulating in cattle and tsetse flies
      in order to understand their distribution and prevalence in livestock/wildlife
      interface areas in the Maasai Steppe. METHODS: A total of 1002 cattle and 886
      tsetse flies were sampled from June 2015 to February 2016 in five villages and
      PCR was conducted to amplify the internal transcribed spacer 1 (ITS1) from
      trypanosomes. All Trypanosoma brucei-positive samples were further tested for the
      presence of the serum resistance-associated (SRA) gene found in human-infective
      trypanosomes using the SRA-LAMP technique. RESULTS: The overall prevalence of
      trypanosome infections was 17.2% in cattle and 3.4% in tsetse flies. Using a
      nested PCR, prevalence and abundance of five trypanosome species, Trypanosoma
      vivax, T. brucei, T. simiae, T. theileri and T. congolense, were determined,
      which varied with season and location. The highest prevalence of the identified
      trypanosome species was recorded at the end of wet season with an exception of T.
      brucei which was high at the beginning of the wet season. No human-infective
      trypanosomes were detected in both cattle and tsetse fly DNA. CONCLUSIONS: This
      study confirms that seasonality and location have a significant contribution to
      the prevalence of trypanosome species in both mammalian and vector hosts. These
      results are important for designing of community-wide vector and disease control
      interventions and planning of sustainable regimes for reduction of the burden of
      trypanosomosis in endemic pastoral areas, such as the Maasai Steppe in northern
      Tanzania.

PMID- 29061161
TI  - Using a genetic/clinical risk score to stop smoking (GeTSS): randomised
      controlled trial.
AB  - BACKGROUND: As genetic tests become cheaper, the possibility of their widespread
      availability must be considered. This study involves a risk score for lung cancer
      in smokers that is roughly 50% genetic (50% clinical criteria). The risk score
      has been shown to be effective as a smoking cessation motivator in hospital
      recruited subjects (not actively seeking cessation services). METHODS: This was
      an RCT set in a United Kingdom National Health Service (NHS) smoking cessation
      clinic. Smokers were identified from medical records. Subjects that wanted to
      participate were randomised to a test group that was administered a gene-based
      risk test and given a lung cancer risk score, or a control group where no risk
      score was performed. Each group had 8 weeks of weekly smoking cessation sessions
      involving group therapy and advice on smoking cessation pharmacotherapy and
      follow-up at 6 months. The primary endpoint was smoking cessation at 6 months.
      Secondary outcomes included ranking of the risk score and other motivators.
      RESULTS: 67 subjects attended the smoking cessation clinic. The 6 months quit
      rates were 29.4%, (10/34; 95% CI 14.1-44.7%) for the test group and 42.9% (12/28;
      95% CI 24.6-61.2%) for the controls. The difference is not significant. However,
      the quit rate for test group subjects with a "very high" risk score was 89% (8/9;
      95% CI 68.4-100%) which was significant when compared with the control group (p =
      0.023) and test group subjects with moderate risk scores had a 9.5% quit rate
      (2/21; 95% CI 2.7-28.9%) which was significantly lower than for above moderate
      risk score 61.5% (8/13; 95% CI 35.5-82.3; p = 0.03). CONCLUSIONS: Only the sub
      group with the highest risk score showed an increased quit rate. Controls and
      test group subjects with a moderate risk score were relatively unlikely to have
      achieved and maintained non-smoker status at 6 months. ClinicalTrials.gov ID
      NCT01176383 (date of registration: 3 August 2010).

PMID- 29061162
TI  - Whole transcriptome analysis of human erythropoietic cells during ontogenesis
      suggests a role of VEGFA gene as modulator of fetal hemoglobin and
      pharmacogenomic biomarker of treatment response to hydroxyurea in beta-type
      hemoglobinopathy patients.
AB  - BACKGROUND: Human erythropoiesis is characterized by distinct gene expression
      profiles at various developmental stages. Previous studies suggest that fetal-to
      adult hemoglobin switch is regulated by a complex mechanism, in which many key
      players still remain unknown. Here, we report our findings from whole
      transcriptome analysis of erythroid cells, isolated from erythroid tissues at
      various developmental stages in an effort to identify distinct molecular
      signatures of each erythroid tissue. RESULTS: From our in-depth data analysis,
      pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its
      gene expression characteristics. Selected VEGFA genomic variants, identified
      through linkage disequilibrium analysis, were explored further for their
      association with elevated fetal hemoglobin levels in beta-type hemoglobinopathy
      patients. Our downstream analysis of non-transfusion-dependent beta-thalassemia
      patients, beta-thalassemia major patients, compound heterozygous sickle cell
      disease/beta-thalassemia patients receiving hydroxyurea as fetal hemoglobin
      augmentation treatment, and non-thalassemic individuals indicated that VEGFA
      genomic variants were associated with disease severity in beta-thalassemia
      patients and hydroxyurea treatment efficacy in SCD/beta-thalassemia compound
      heterozygous patients. CONCLUSIONS: Our findings suggest that VEGFA may act as a
      modifier gene of human globin gene expression and, at the same time, serve as a
      genomic biomarker in beta-type hemoglobinopathy disease severity and hydroxyurea
      treatment efficacy.

PMID- 29061165
TI  - Sustained endocrine profiles of a girl with WAGR syndrome.
AB  - BACKGROUND: Wilms tumor, aniridia, genitourinary anomalies and mental retardation
      (WAGR) syndrome is a rare genetic disorder caused by heterozygous deletions of
      WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated
      with hyperphagia and obesity in both humans and animal models; however,
      neuroendocrine and epigenetic profiles of individuals with WAGR syndrome remain
      to be determined. CASE PRESENTATION: We report a 5-year-old girl with the typical
      phenotype of WAGR syndrome. She showed profound delays in physical growth, motor
      and cognitive development without signs of obesity. Array comparative genome
      hybridization (CGH) revealed that she carried a 14.4 Mb deletion at 11p14.3p12,
      encompassing the WT1, PAX6 and BDNF genes. She experienced recurrent hypoglycemic
      episodes at 5 years of age. Insulin tolerance and hormonal loading tests showed
      normal hypothalamic responses to the hypoglycemic condition and other
      stimulations. Methylation analysis for freshly prepared DNA from peripheral
      lymphocytes using the pyro-sequencing-based system showed normal patterns of
      methylation at known imprinting control regions. CONCLUSIONS: Children with WAGR
      syndrome may manifest profound delay in postnatal growth through unknown
      mechanisms. Epigenetic factors and growth-associated genes in WAGR syndrome
      remain to be characterized.

PMID- 29061164
TI  - Moroccan strains of Leishmania major and Leishmania tropica differentially impact
      on nitric oxide production by macrophages.
AB  - BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease
      caused by protozoa of the genus Leishmania. In Morocco, CL is a public health
      problem mainly caused by Leishmania major and Leishmania tropica, which are
      responsible for zoonotic and anthroponotic CL, respectively. Macrophages are the
      primary cells infected by Leishmania parasites and their capacity to produce
      nitric oxide (NO) is of critical importance for parasite elimination. To our
      knowledge, the role of NO on autochthonous infections has never been investigated
      before. In this study, we evaluated in vitro the capacity of autochthonous
      primary dermotropic strains of L. major and L. tropica to modulate NO production
      by J774-macrophages and determine the sensitivity of both species to exogenous
      NO. METHODS: The infectivity of the J774 cell line was analyzed by optical
      microscopy. NO production by macrophages was measured by the Griess method. The
      sensitivity to NO by the two strains was assessed by the MTT assay using NO
      donors. RESULTS: Our results show that the percentage of infected macrophages and
      the average number of parasites per macrophage were similar for L. major and L.
      tropica strains. While L. tropica significantly inhibited NO production induced
      by LPS and IFN-gamma stimulation in J774 macrophages, L. major did not affect it.
      However, soluble Leishmania antigens (SLAs) from both autochthonous primary
      strains significantly inhibited the production of NO by J774-macrophages in a
      dose-dependent manner. Finally, our results demonstrated that promastigotes and
      amastigotes from both strains are sensitive to SNAP NO donor in a dose-dependent
      manner, although L. tropica demonstrated an increased sensitivity. CONCLUSIONS:
      Our results suggest a differential ability of L. major and L. tropica strains to
      modulate the capacity of macrophages to produce NO. The increased ability of L.
      tropica to inhibit NO production by macrophages might come as a necessity due to
      its higher sensitivity to NO donor. Our results provide one explanation for the
      tendency of L. tropica to cause chronic lesions and may contribute to the
      different physiopathology of CL in Morocco.

PMID- 29061163
TI  - An integrative review of the methodology and findings regarding dietary adherence
      in end stage kidney disease.
AB  - BACKGROUND: Dietary modification is an important component of the management of
      end stage kidney disease (ESKD). The diet for ESKD involves modifying energy and
      protein intake, and altering sodium, phosphate, potassium and fluid intake. There
      have been no comprehensive reviews to date on this topic. The aims of this
      integrative review were to (i) describe the methods used to measure dietary
      adherence (ii) determine the rate of dietary adherence and (iii) describe factors
      associated with dietary adherence in ESKD. METHODS: The Web of Science and Scopus
      databases were searched using the search terms 'adherence' and 'end stage kidney
      disease'. Of the 787 potentially eligible papers retrieved, 60 papers of 24,743
      patients were included in this review. Of these papers, 44 reported the rate of
      dietary adherence and 44 papers described factors associated with adherence.
      RESULTS: Most of the evidence regarding dietary adherence is derived from studies
      of hemodialysis patients (72% of patients). The most common method of measuring
      dietary adherence in ESKD was subjective techniques (e.g. food diaries or
      adherence questionnaires). This was followed by indirect methods (e.g. serum
      potassium, phosphate or interdialytic weight gain). The weighted mean adherence
      rate to ESKD dietary recommendations was 31.5% and 68.5% for fluid
      recommendations. Adherence to protein, sodium, phosphate, and potassium
      recommendations were highly variable due to differences in measurement methods
      used, and were often derived from a limited evidence base. Socioeconomic status,
      age, social support and self-efficacy were associated with dietary adherence.
      However, factors such as taste, the impact of the diet on social eating
      occasions; and dietetic staffing also appear to play a role in dietary adherence.
      CONCLUSION: Dietary adherence rates in people with ESKD are suboptimal. Further
      research is required on dietary adherence in patients with ESKD from different
      social, educational, economic and ethnic groups. This research may identify other
      factors which may impact upon adherence, and could be used to inform the design
      of future strategies to improve dietary adherence. Future research that reports
      not just the rate of adherence to individual components of the nutrient
      prescription but also the overall quality of the diet would be useful.

PMID- 29061166
TI  - Toxoplasma gondii seroprevalence and genotype diversity in select wildlife
      species from the southeastern United States.
AB  - BACKGROUND: Toxoplasma gondii is a widespread protozoan parasite that infects
      humans and other animals. Previous studies indicate some genotypes of T. gondii
      are more frequently isolated in wildlife than agricultural animals, suggesting a
      wild/feral animal diversity model. To determine seroprevalence and genetic
      diversity of T. gondii in southeastern US wildlife, we collected sera from 471
      wild animals, including 453 mammals and 18 birds, between 2011 and 2014. These
      serum samples were assayed for T. gondii infection using the modified
      agglutination test (MAT). Heart or tongue tissues from 66 seropositive animals
      were bioassayed in mice and 19 isolates were obtained. The isolated parasites
      were genotyped by the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method employing 10 genetic markers. RESULTS: One hundred
      and ninety-six of 471 samples (41.6%) had a titer >=1:32 and were considered
      positive for T. gondii infection. Of 453 mammals, 195 (43%) were seropositive,
      whereas only one (5.6%) of 18 birds was seropositive. The seroprevalence in
      mammals was significantly higher than in the birds. Mammalian hosts with adequate
      samples size (>= 20) comprised white-tailed deer (n = 241), feral hogs (n = 100),
      raccoons (n = 34) and coyotes (n = 22), with seroprevalences of 41.0%, 51.0%,
      50.0% and 72.7%, respectively. Coyotes had significantly higher seroprevalence
      than the white-tailed deer. Genotyping revealed five distinct genotypes,
      including the ToxoDB PCR-RFLP genotype #5 (a.k.a type 12) for 15 isolates,
      genotype #3 (a.k.a. type II) for 1 isolate, and genotypes #154, #167 and #216,
      each for 1 isolate. The results showed moderate to high infection rates of T.
      gondii in white-tailed deer, feral hogs, raccoons and coyotes. Genotyping results
      indicated limited genetic diversity and a dominance of genotype #5, which has
      been reported as a major type in wildlife in North America. CONCLUSIONS: We
      conclude that T. gondii infection is common in game animals (white-tailed deer
      and feral hogs) in the southeastern US, which may pose a food safety risk to
      humans. Further research is necessary to understand T. gondii transmission from
      wildlife to farm animals and humans.

PMID- 29061168
TI  - Silence is deadly: a cluster-randomised controlled trial of a mental health help
      seeking intervention for young men.
AB  - BACKGROUND: Young men are consistently less likely to seek help for mental health
      problems than their female peers. This is particularly concerning given the high
      rates of suicide among male adolescents. The school system has been identified as
      an ideal setting for the implementation of prevention and early intervention
      programs for young people. The current trial aims to determine the effectiveness
      of the Silence is Deadly program in increasing positive help-seeking intentions
      for mental health problems and suicide among male secondary school students.
      METHODS: This study is a two-arm, cluster-randomised, controlled trial that will
      compare the Silence is Deadly program to a wait-list control condition. Eight
      Australian high schools will be recruited to the trial, with male students in
      grades 11 and 12 (16 to 18 years of age) targeted for participation. The program
      is an innovative male-tailored suicide prevention intervention, comprising a
      presentation that emphasises role-modelling and legitimises help-seeking for
      personal and emotional problems, and a brief video that features celebrity
      athletes who counter existing male norms around help-seeking and encourage
      communication about personal and emotional issues. The program also includes a
      discussion of how to help a friend in distress and ends with a question and
      answer session. The primary outcome measure for the current study is help-seeking
      intentions. Secondary outcomes include help-seeking behaviour, help-seeking
      attitudes, help-seeking stigma, mental health symptoms, and suicidal ideation.
      Data will be collected pre-intervention, post-intervention, and at 3-month follow
      up. Primary analyses will compare changes in help-seeking intentions for the
      intervention condition relative to the wait-list control condition using mixed
      effects repeated-measures analyses that account for clustering within schools.
      DISCUSSION: If proven to be effective, this targeted help-seeking intervention
      for adolescent males, which is currently only delivered in one jurisdiction,
      could be more widely delivered in Australian high schools. The Silence is Deadly
      program has the potential to significantly contribute to the mental health of
      young men in Australia by improving help-seeking for suicidality and mental
      health problems, allowing this population to better access treatment and support
      sooner. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry,
      ACTRN12617000658314 . Registered on 8 May 2017.

PMID- 29061167
TI  - Genome-wide profiling of transcribed enhancers during macrophage activation.
AB  - BACKGROUND: Macrophages are sentinel cells essential for tissue homeostasis and
      host defence. Owing to their plasticity, macrophages acquire a range of
      functional phenotypes in response to microenvironmental stimuli, of which M(IFN
      gamma) and M(IL-4/IL-13) are well known for their opposing pro- and anti
      inflammatory roles. Enhancers have emerged as regulatory DNA elements crucial for
      transcriptional activation of gene expression. RESULTS: Using cap analysis of
      gene expression and epigenetic data, we identify on large-scale transcribed
      enhancers in bone marrow-derived mouse macrophages, their time kinetics, and
      target protein-coding genes. We observe an increase in target gene expression,
      concomitant with increasing numbers of associated enhancers, and find that genes
      associated with many enhancers show a shift towards stronger enrichment for
      macrophage-specific biological processes. We infer enhancers that drive
      transcriptional responses of genes upon M(IFN-gamma) and M(IL-4/IL-13) macrophage
      activation and demonstrate stimuli specificity of regulatory associations.
      Finally, we show that enhancer regions are enriched for binding sites of
      inflammation-related transcription factors, suggesting a link between stimuli
      response and enhancer transcriptional control. CONCLUSIONS: Our study provides
      new insights into genome-wide enhancer-mediated transcriptional control of
      macrophage genes, including those implicated in macrophage activation, and offers
      a detailed genome-wide catalogue of transcribed enhancers in bone marrow-derived
      mouse macrophages.

PMID- 29061171
TI  - Use of a bioinformatic-assisted primer design strategy to establish a new nested
      PCR-based method for Cryptosporidium.
AB  - BACKGROUND: The accurate tracking of Cryptosporidium in faecal, water and/or soil
      samples in water catchment areas is central to developing strategies to manage
      the potential risk of cryptosporidiosis transmission to humans. Various PCR
      assays are used for this purpose. Although some assays achieve specific
      amplification from Cryptosporidium DNA in animal faecal samples, some do not.
      Indeed, we have observed non-specificity of some oligonucleotide primers in the
      small subunit of nuclear ribosomal RNA gene (SSU), which has presented an
      obstacle to the identification and classification of Cryptosporidium species and
      genotypes (taxa) from faecal samples. RESULTS: Using a novel bioinformatic
      approach, we explored all available Cryptosporidium genome sequences for new and
      diagnostically-informative, multi-copy regions to specifically design
      oligonucleotide primers in the large subunit of nuclear ribosomal RNA gene (LSU)
      as a basis for an effective nested PCR-based sequencing method for the
      identification and/or classification of Cryptosporidium taxa. CONCLUSION: This
      newly established PCR, which has high analytical specificity and sensitivity, is
      now in routine use in our laboratory, together with other assays developed by
      various colleagues. Although the present bioinformatic workflow used here was for
      the specific design of primers in nuclear DNA of Cryptosporidium, this approach
      should be broadly applicable to many other microorganisms.

PMID- 29061170
TI  - Translating recent results from the Cardiovascular Outcomes Trials into clinical
      practice: recommendations from the Central and Eastern European Diabetes Expert
      Group (CEEDEG).
AB  - AIMS: These recommendations aim to improve care for patients with type 2 diabetes
      (T2D) at high cardiovascular (CV) risk in Central and Eastern Europe.
      Cardiovascular disease (CVD) and/or chronic kidney disease (CKD) are major
      interdependent comorbidities in patients with T2D, accounting for 50% of
      mortality. Following recent CV outcomes trial (CVOT) results, including those
      from EMPA-REG OUTCOME(r), LEADER(r), SUSTAINTM-6 and, most recently, the CANVAS
      study, it is essential to develop regional expert consensus recommendations to
      aid physicians in interpreting these newest data to clinical practice. METHODS:
      The Central and Eastern European Diabetes Expert Group (CEEDEG) followed a Delphi
      method to develop treatment algorithms to aid physicians in the clinical
      management of patients with T2D at high CV risk. RESULTS: In light of the latest
      CVOT results, and in particular the EMPA-REG OUTCOME(r) and LEADER(r) trials, the
      diagnosis, assessment, treatment choice and monitoring of patients with T2D and
      established CVD and/or CKD have been considered together with existing guidelines
      and presented in two reference algorithms. In addition, adherence, special
      prescribing considerations and a proposed multidisciplinary management approach
      have been discussed and are presented with the proposed algorithms. CONCLUSIONS:
      The latest available high-level evidence on glucose-lowering drugs has enabled
      CEEDEG to develop practical consensus recommendations for patients with
      established CVD and/or CKD. These recommendations represent an update to
      international and country-level guidelines used for these patients, with the aim
      of providing a resource not only to endocrinologists, but to cardiologists,
      nephrologists and primary care physicians in the region.

PMID- 29061169
TI  - The effect of transcranial direct current stimulation (tDCS) on locomotion and
      balance in patients with chronic stroke: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Following stroke, patients are often left with hemiparesis that
      reduces balance and gait capacity. A recent, non-invasive technique, transcranial
      direct current stimulation, can be used to modify cortical excitability when used
      in an anodal configuration. It also increases the excitability of spinal neuronal
      circuits involved in movement in healthy subjects. Many studies in patients with
      stroke have shown that this technique can improve motor, sensory and cognitive
      function. For example, anodal tDCS has been shown to improve motor performance of
      the lower limbs in patients with stroke, such as voluntary quadriceps strength,
      toe-pinch force and reaction time. Nevertheless, studies of motor function have
      been limited to simple tasks. Surprisingly, the effects of tDCS on the locomotion
      and balance of patients with chronic stroke have never been evaluated. In this
      study, we hypothesise that anodal tDCS will improve balance and gait parameters
      in patients with chronic stroke-related hemiparesis through its effects at
      cortical and spinal level. METHODS/DESIGN: This is a prospective, randomised,
      placebo-controlled, double-blinded, single-centre, cross-over study over 36
      months. Forty patients with chronic stroke will be included. Each patient will
      participate in three visits: an inclusion visit, and two visits during which they
      will all undergo either one 30-min session of transcranial direct current
      stimulation or one 30-min session of placebo stimulation in a randomised order.
      Evaluations will be carried out before, during and twice after stimulation. The
      primary outcome is the variability of the displacement of the centre of mass
      during gait and a static-balance task. Secondary outcomes include clinical and
      functional measures before and after stimulation. A three-dimensional gait
      analysis, and evaluation of static balance on a force platform will be also
      conducted before, during and after stimulation. DISCUSSION: These results should
      constitute a useful database to determine the aspects of complex motor function
      that are the most improved by transcranial direct current stimulation in patients
      with hemiparesis. It is the first essential step towards validating this
      technique as a treatment, coupled with task-oriented training. TRIAL
      REGISTRATION: ClinicalTrials.gov, ID: NCT02134158 . First received on 18 December
      2013; last updated on 14 September 2016. Other study ID numbers: P120135 /
      AOM12126, 2013-A00952-43.

PMID- 29061172
TI  - NuA4 histone acetyltransferase activity is required for H4 acetylation on a
      dosage-compensated monosomic chromosome that confers resistance to fungal toxins.
AB  - BACKGROUND: The major human fungal pathogen Candida albicans possesses a diploid
      genome, but responds to growth in challenging environments by employing
      chromosome aneuploidy as an adaptation mechanism. For example, we have shown that
      C. albicans adapts to growth on the toxic sugar L-sorbose by transitioning to a
      state in which one chromosome (chromosome 5, Ch5) becomes monosomic. Moreover,
      analysis showed that while expression of many genes on the monosomic Ch5 is
      altered in accordance with the chromosome ploidy, expression of a large fraction
      of genes is increased to the normal diploid level, presumably compensating for
      gene dose. RESULTS: In order to understand the mechanism of the apparent dosage
      compensation, we now report genome-wide ChIP-microarray assays for a sorbose
      resistant strain harboring a monosomic Ch5. These data show a significant
      chromosome-wide elevation in histone H4 acetylation on the mCh5, but not on any
      other chromosome. Importantly, strains lacking subunits of the NuA4 H4 histone
      acetyltransferase complex, orthologous to a complex previously shown in
      Drosophila to be associated with a similar gene dosage compensation mechanism,
      did not show an increase in H4 acetylation. Moreover, loss of NuA4 subunits
      severely compromised the adaptation to growth on sorbose. CONCLUSIONS: Our
      results are consistent with a model wherein chromosome-wide elevation of H4
      acetylation mediated by the NuA4 complex plays a role in increasing gene
      expression in compensation for gene dose and adaption to growth in a toxic
      environment.

PMID- 29061173
TI  - Socioeconomic inequalities in health among Swedish adolescents - adding the
      subjective perspective.
AB  - BACKGROUND: Socioeconomic inequalities in adolescent health predict future
      inequalities in adult health. Subjective measures of socioeconomic status (SES)
      may contribute with an increased understanding of these inequalities. The aim of
      this study was to investigate socioeconomic health inequalities using both a
      subjective and an objective measure of SES among Swedish adolescents. METHOD:
      Cross-sectional HBSC-data from 2002 to 2014 was used with a total sample of
      23,088 adolescents aged 11-15 years. Three measures of self-rated health
      (dependent variables) were assessed: multiple health complaints, life
      satisfaction and health perception. SES was measured objectively by the Family
      Affluence Scale (FAS) and subjectively by "perceived family wealth" (independent
      variables). The trend for health inequalities was investigated descriptively with
      independent t-tests and the relationship between independent and dependent
      variables was investigated with multiple logistic regression analysis. Gender,
      age and survey year was considered as possible confounders. RESULTS: Subjective
      SES was more strongly related to health outcomes than the objective measure
      (FAS). Also, the relation between FAS and health was weakened and even reversed
      (for multiple health complaints) when subjective SES was tested simultaneously in
      regression models (FAS OR: 1.03, CI: 1.00;1.06 and subjective SES OR: 0.66, CI:
      0.63;0.68). CONCLUSIONS: The level of socioeconomic inequalities in adolescent
      health varied depending on which measure that was used to define SES. When
      focusing on adolescents, the subjective appraisals of SES is important to
      consider because they seem to provide a stronger tool for identifying
      inequalities in health for this group. This finding is important for policy
      makers to consider given the persistence of health inequalities in Sweden and
      other high-income countries.

PMID- 29061174
TI  - De novo chromosome 7q36.1q36.2 triplication in a child with developmental delay,
      growth failure, distinctive facial features, and multiple congenital anomalies: a
      case report.
AB  - BACKGROUND: Studying human genome using chromosomal microarrays has significantly
      improved the accuracy and yield of diagnosing genomic disorders. Chromosome 7q36
      deletions and duplications are rare genomic disorders that have been reported in
      a limited number of children with developmental delay, growth retardation, and
      congenital malformation. Altered dosage of SHH and HLXB9, both located in 7q36.3,
      is believed to play roles in the phenotypes associated with these rearrangements.
      In this report we describe a child with 7q36.1q36.2 triplication that is proximal
      to the 7q36.3 region. In addition to the clinical description, we discuss the
      genes located in the triplicated region. CASE PRESENTATION: We report a 22 month
      old male child with a de novo 1.35 Mb triplication at 7q36.1q36.2. His prenatal
      course was complicated by oligohydramnios, intrauterine growth restriction, and
      decreased fetal movement. Hypotonia, respiratory distress, and feeding difficulty
      were observed in the neonatal period. He also had developmental delay,
      cardiovascular malformation, growth failure with microcephaly, short stature, and
      underweight, sensorineural hearing loss, myopia, astigmatism, cryptorchidism,
      hypospadias, microphallus, lower extremity length discrepancy, bifid uvula,
      single palmer creases, and distinctive facial features including straight
      eyebrows, ptosis, up-slanted palpebral fissures, broad nasal bridge, low-set and
      posteriorly rotated ears, small mouth with thick lower lip, microretrognathia,
      and high-arched palate. CONCLUSIONS: The child presented here had developmental
      delay, distinctive facial features, multiple congenital anomalies, and
      7q36.1q36.2 triplication. This triplication, which was found to be de novo, has
      not been previously described and is believed to result in the observed
      phenotype. The triplicated region harbors the GALNTL5, GALNT11, KMT2C, XRCC2, and
      ACTR3B genes. GALNT11 encodes a membrane-bound polypeptide N
      acetylgalactosaminyltransferase that can O-glycosylate NOTCH1 leading to the
      activation of the Notch signaling pathway. Therefore, increased GALNT11 dosage
      can potentially alter the Notch signaling pathway explaining the pathogenicity of
      7q36 triplication. Studying further cases with similar genomic rearrangements is
      needed to make final conclusions about the pathogenicity of this triplication.

PMID- 29061176
TI  - Correction to: longitudinal associations between built environment
      characteristics and changes in active commuting.

PMID- 29061175
TI  - Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial
      chemoembolization for massive unresectable hepatocellular carcinoma: a
      prospective non-randomized study.
AB  - BACKGROUND: Transarterial chemoembolization (TACE) is recommended as the standard
      care for unresectable hepatocellular carcinoma (HCC) at Barcelona Clinic Liver
      Cancer (BCLC) stage A-B. However, the efficacy of TACE on large (>= 10 cm) stage
      A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion
      chemotherapy (HAIC) might be a better first-line treatment of this disease.
      Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX
      (mFOLFOX) regimen and those of TACE in patients with massive unresectable HCC.
      METHODS: A prospective, non-randomized, phase II study was conducted on patients
      with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX
      regimen (oxaliplatin, 85 mg/m2 intra-arterial infusion; leucovorin, 400 mg/m2
      intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400
      mg/m2 continuous infusion) every 3 weeks and TACE with 50 mg of epirubicin, 50 mg
      of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles.
      The tumor responses, time-to-progression (TTP), and safety were assessed.
      RESULTS: A total of 79 patients were recruited for this study: 38 in the HAIC
      group and 41 in the TACE group. The HAIC group exhibited higher partial response
      and disease control rates than did the TACE group (52.6% vs. 9.8%, P < 0.001;
      83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were
      5.87 and 3.6 months (hazard radio [HR] = 2.35, 95% confidence interval [CI] =
      1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group
      underwent resection (10 vs. 3, P = 0.033). The proportions of grade 3-4 adverse
      events (AE) and serious adverse events (SAE) were lower in the HAIC group than in
      the TACE group (grade 3-4 AEs: 13 vs. 27, P = 0.007; SAEs: 6 vs. 15, P = 0.044).
      More patients in the TACE group than in the HAIC group had the study treatment
      terminated early due to intolerable treatment-related adverse events or the
      withdrawal of consent (10 vs. 2, P = 0.026). CONCLUSIONS: HAIC with mFOLFOX
      yielded significantly better treatment responses and less serious toxicity than
      did TACE. HAIC might represent a feasible and promising first-line treatment for
      patients with massive unresectable HCC.

PMID- 29061177
TI  - Community analysis of the abundance and diversity of mosquito species (Diptera:
      Culicidae) in three European countries at different latitudes.
AB  - BACKGROUND: Studies on mosquito species diversity in Europe often focus on a
      specific habitat, region or country. Moreover, different trap types are used for
      these sampling studies, making it difficult to compare and validate results
      across Europe. To facilitate comparisons of trapping sites and community
      analysis, the present study used two trap types for monitoring mosquito species
      diversity in three habitat types for three different countries in Europe.
      METHODS: Mosquitoes were trapped using Biogents Sentinel (BGS), and Mosquito
      Magnet Liberty Plus (MMLP) traps at a total of 27 locations in Sweden, the
      Netherlands and Italy, comprising farm, peri-urban and wetland habitats. From
      July 2014 to June 2015 all locations were sampled monthly, except for the winter
      months. Indices of species richness, evenness and diversity were calculated, and
      community analyses were carried out with non-metric multidimensional scaling
      (NMDS) techniques. RESULTS: A total of 11,745 female mosquitoes were trapped
      during 887 collections. More than 90% of the mosquitoes belonged to the genera
      Culex and Aedes, with Culex pipiens being the most abundant species. The highest
      mosquito diversity was found in Sweden. Within Sweden, species diversity was
      highest in wetland habitats, whereas in the Netherlands and Italy this was
      highest at farms. The NMDS analyses showed clear differences in mosquito
      communities among countries, but not among habitat types. The MMLP trapped a
      higher diversity of mosquito species than the BGS traps. Also, MMLP traps trapped
      higher numbers of mosquitoes, except for the genera Culex and Culiseta in Italy.
      CONCLUSIONS: A core mosquito community could be identified for the three
      countries, with Culex pipiens as the most abundant species. Differences in
      mosquito species communities were more defined by the three countries included in
      the study than by the three habitat types. Differences in mosquito community
      composition across countries may have implications for disease emergence and
      further spread throughout Europe. Future research should, therefore, focus on how
      field data of vector communities can be incorporated into models, to better
      assess the risk of mosquito-borne disease outbreaks.

PMID- 29061178
TI  - Intensive procedure preferences at the end of life (EOL) in older Latino adults
      with end stage renal disease (ESRD) on dialysis.
AB  - BACKGROUND: Latinos in the U.S. are almost twice as likely to progress to End
      Stage Renal disease (ESRD) compared to non-Latino whites. Patients with ESRD on
      dialysis experience high morbidity, pre-mature mortality and receive intensive
      procedures at the end of life (EOL). This study explores intensive procedure
      preferences at the EOL in older Latino adults. METHODS: Seventy-three community
      dwelling Spanish- and English-Speaking Latinos over the age of 60 with and
      without ESRD participated in this study. Those without ESRD (n = 47) participated
      in one of five focus group sessions, and those with ESRD on dialysis (n = 26)
      participated in one-on-one semi-structured interviews. Focus group and individual
      participants answered questions regarding intensive procedures at the EOL.
      Recurring themes were identified using standard qualitative content-analysis
      methods. Participants also completed a brief survey that included demographics,
      language preference, health insurance coverage, co-morbidities, Emergency
      Department visits and functional limitations. RESULTS: The majority of
      participants were of Mexican origin with mean age of 70, and there were more
      female participants in the non-ESRD group, compared to the ESRD dialysis
      dependent group. The dialysis group reported a higher number of co-morbidities
      and functional limitations. Nearly 69% of those in the dialysis group reported
      one or more emergency department visits in the past year, compared to 38% in the
      non-ESRD group. Primary themes centered on 1) The acceptability of a "natural"
      versus "invasive" procedure 2) Cultural traditions and family involvement 3)
      Level of trust in physicians and autonomy in decision-making. CONCLUSION: Our
      results highlight the need for improved patient- and family-centered approaches
      to better understand intensive procedure preferences at the EOL in this
      underserved population of older adults.

PMID- 29061179
TI  - Effect of whey protein supplementation on levels of endocannabinoids and some of
      metabolic risk factors in obese women on a weight-loss diet: a study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: Besides the effects of dietary long chain PUFA on circulating
      endocannabinoids concentrations, the impact of other nutrients on these system is
      not known and, whether changes in plasma endocannabinoids levels correlated with
      changes in body composition and biochemical metabolic risk factors in obese
      individuals, however, still remains to be characterized. METHODS: We will conduct
      a 2 months' open label, parallel-group, randomized controlled trial to determine
      the effect of whey protein supplementation on levels of endocannabinoids,
      glycemic and lipid profile, inflammatory factors, adipocytokines and body
      composition in 60 premenopausal obese women on a weight-loss diet. CONCLUSION:
      Due to strong relationship between endocannabinoids level and insulin resistance
      and obesity, in this trial, we will illustrate the other benefits of weight loss
      diet on health and metabolic risk factors. Also for the first, the effects of
      simultaneous weight loss diet and whey protein supplementation on these variables
      will be determined. TRIAL REGISTRATION: Iranian Registry of Clinical Trials
      IRCT2017021410181N8 .

PMID- 29061181
TI  - Paroxysmal atrial fibrillation recognition based on multi-scale wavelet alpha
      entropy.
AB  - BACKGROUND: This study proposed an effective method based on the wavelet multi
      scale alpha-entropy features of heart rate variability (HRV) for the recognition
      of paroxysmal atrial fibrillation (PAF). This new algorithm combines wavelet
      decomposition and non-linear analysis methods. The PAF signal, the signal distant
      from PAF, and the normal sinus signals can be identified and distinguished by
      extracting the characteristic parameters from HRV signals and analyzing their
      quantification indexes. The original ECG signals for QRS detection and HRV signal
      extraction are first processed. The features from the HRV signals are extracted
      as feature vectors using the wavelet multi-scale entropy. A support vector
      machine-based classifier is used for PAF prediction. RESULTS: The performance of
      the proposed method in predicting PAF episodes is evaluated with 100 signals from
      the MIT-BIT PAF prediction database. With regard to the dynamics and uncertainty
      of PAF signals, our proposed method obtains the values of 92.18, 94.88, and
      89.48% for the evaluation criteria of correct rate, sensitivity, and specificity,
      respectively. CONCLUSIONS: Our proposed method presents better results than the
      existing studies based on time domain, frequency domain, and non-linear methods.
      Thus, our method shows considerable potential for clinical monitoring and
      treatment.

PMID- 29061180
TI  - Flow cytometric immunobead assay for quantitative detection of platelet
      autoantibodies in immune thrombocytopenia patients.
AB  - BACKGROUND: Platelet autoantibody detection is critical for immune
      thrombocytopenia (ITP) diagnosis and prognosis. Therefore, we aimed to establish
      a quantitative flow cytometric immunobead assay (FCIA) for ITP platelet
      autoantibodies evaluation. METHODS: Capture microbeads coupled with anti-GPIX, 
      GPIb, -GPIIb, -GPIIIa and P-selectin antibodies were used to bind the platelet
      bound autoantibodies complex generated from plasma samples of 250 ITP patients,
      163 non-ITP patients and 243 healthy controls, a fluorescein isothiocyanate
      (FITC)-conjugated secondary antibody was the detector reagent and mean
      fluorescence intensity (MFI) signals were recorded by flow cytometry. Intra- and
      inter-assay variations of the quantitative FCIA assay were assessed. Comparisons
      of the specificity, sensitivity and accuracy between quantitative and qualitative
      FCIA or monoclonal antibody immobilization of platelet antigen (MAIPA) assay were
      performed. Finally, treatment process was monitored by our quantitative FCIA in 8
      newly diagnosed ITPs. RESULTS: The coefficient of variations (CV) of the
      quantitative FCIA assay were respectively 9.4, 3.8, 5.4, 5.1 and 5.8% for anti
      GPIX, -GPIb, -GPIIIa, -GPIIb and -P-selectin autoantibodies. Elevated levels of
      autoantibodies against platelet glycoproteins GPIX, GPIb, GPIIIa, GPIIb and P
      selectin were detected by our quantitative FCIA in ITP patients compared to non
      ITP patients or healthy controls. The sensitivity, specificity and accuracy of
      our quantitative assay were respectively 73.13, 81.98 and 78.65% when combining
      all 5 autoantibodies, while the sensitivity, specificity and accuracy of MAIPA
      assay were respectively 41.46, 90.41 and 72.81%. CONCLUSIONS: A quantitative FCIA
      assay was established. Reduced levels of platelet autoantibodies could be
      confirmed by our quantitative FCIA in ITP patients after corticosteroid
      treatment. Our quantitative assay is not only good for ITP diagnosis but also for
      ITP treatment monitoring.

PMID- 29061182
TI  - Editing inducer elements increases A-to-I editing efficiency in the mammalian
      transcriptome.
AB  - BACKGROUND: Adenosine to inosine (A-to-I) RNA editing has been shown to be an
      essential event that plays a significant role in neuronal function, as well as
      innate immunity, in mammals. It requires a structure that is largely double
      stranded for catalysis but little is known about what determines editing
      efficiency and specificity in vivo. We have previously shown that some editing
      sites require adjacent long stem loop structures acting as editing inducer
      elements (EIEs) for efficient editing. RESULTS: The glutamate receptor subunit A2
      is edited at the Q/R site in almost 100% of all transcripts. We show that
      efficient editing at the Q/R site requires an EIE in the downstream intron,
      separated by an internal loop. Also, other efficiently edited sites are flanked
      by conserved, highly structured EIEs and we propose that this is a general
      requisite for efficient editing, while sites with low levels of editing lack
      EIEs. This phenomenon is not limited to mRNA, as non-coding primary miRNAs also
      use EIEs to recruit ADAR to specific sites. CONCLUSIONS: We propose a model where
      two regions of dsRNA are required for efficient editing: first, an RNA stem that
      recruits ADAR and increases the local concentration of the enzyme, then a
      shorter, less stable duplex that is ideal for efficient and specific catalysis.
      This discovery changes the way we define and determine a substrate for A-to-I
      editing. This will be important in the discovery of novel editing sites, as well
      as explaining cases of altered editing in relation to disease.

PMID- 29061183
TI  - The effects of EPA and DHA enriched fish oil on nutritional and immunological
      markers of treatment naive breast cancer patients: a randomized double-blind
      controlled trial.
AB  - BACKGROUND: We evaluated the effects of eicosapentaenoic (EPA) and
      docosahexaenoic (DHA) acids enriched fish oil (FO) on nutritional and
      immunological parameters of treatment naive breast cancer patients. METHODS: In a
      randomized double blind controlled trial, the FO group (FG) patients were
      supplemented with 2 g/ day of FO concentrate containing 1.8 g of n-3 fatty acids
      during 30 days. The placebo group (PG) received 2 g/ day of mineral oil. At
      baseline and after the intervention, plasma levels of n-3 fatty acids, dietary
      intake, weight, body composition, biochemical and immunological markers were
      assessed. RESULTS: At the end of the intervention period, no between group
      differences were observed regarding anthropometric parameters. There was a
      significant increase in the plasma phospholipid EPA (p = 0.004), DHA (p = 0.007)
      of the FG patients. In FG patients the percentages of peripheral blood CD4+ T
      lymphocytes and serum high sensitivity C-reactive protein (hsCRP) levels were
      maintained while in PG patients there was a significant increase in hsCRP (p =
      0.024). We also observed a significant reduction in the percentage of CD4+ T
      lymphocytes in the peripheral blood (p = 0.042) of PG patients. No changes in
      serum proinflammatory cytokine and prostaglandin E2 levels were observed.
      CONCLUSIONS: Supplementation of newly diagnosed breast cancer patients with EPA
      and DHA led to a significant change in the composition of plasma fatty acids,
      maintained the level of CD4+ T cells and serum levels of hsCRP, suggestive of a
      beneficial effect on the immune system and less active inflammatory response.
      TRIAL REGISTRATION: Brazilian Clinical Trials Registry (REBEC): RBR-2b2hqh.
      Registered 29 April 2013, retrospectively registered.

PMID- 29061184
TI  - Assessment of reverse remodeling predicted by myocardial deformation on tissue
      tracking in patients with severe aortic stenosis: a cardiovascular magnetic
      resonance imaging study.
AB  - BACKGROUND: The technique of tissue tracking with balanced steady-state free
      precession cine sequences was introduced, and allowed myocardial strain to be
      derived directly, offering advantages over traditional myocardial tagging. The
      aim of this study was to evaluate the correlation between reverse remodeling as
      an outcome and left ventricular strain using cardiovascular magnetic resonance
      imaging (CMR) tissue tracking, and to evaluate prediction of reverse remodeling
      by myocardial deformation in patients with severe aortic stenosis (AS). METHODS:
      We enrolled 63 patients with severe AS and normal left ventricular (LV) systolic
      function (ejection fraction > 60%), who underwent both CMR and transthoracic
      echocardiography (Echo) before surgical aortic valve replacement (AVR). CMR at
      1.5 T, including non and post-contrast T1 mapping for extracellular volume (ECV),
      was carried out to define the amount of myocardial fibrosis. Cardiac Performance
      Analysis software was used to derive myocardial deformation as strain parameters
      from three short-axis cine views (basal, mid and apical levels) and apical 2, 3,
      and 4 chamber views. The primary outcome was reverse remodeling, as evaluated by
      regression of left ventricular mass index (LVMI). RESULTS: Median follow-up was
      28.8 months (interquartile range 11.3-38.3 months). As evaluated by LVMI between
      baseline and follow-up, mass regression was significantly improved after AVR
      (baseline 145.9 +/- 37.0 [g/m2] vs. follow-up 97.7 +/- 22.2[g/m2], p < 0.001).
      Statistically significant Pearson's correlations with LVMI regression were
      observed for longitudinal global strain (r = -0.461, p < 0.001), radial strain (r
      = 0.391, p = 0.002), and circumferential strain (r = -0.334, p = 0.009). A simple
      linear regression analysis showed that all strain parameters could predict the
      amount of LVMI regression (P < 0.05), as well as non-contrast T1 value (beta = 
      0.314, p < 0.001) and ECV (beta = -2.546, p = 0.038). However, ECV had the lowest
      predictive power (multiple r2 = 0.071). Multiple regression analysis showed
      strain could independently predict the amount of LVMI regression and the
      longitudinal global strain (beta = -3.335, p < 0.001). CONCLUSION: Longitudinal
      global strain measured by CMR tissue tracking as a technique was correlated with
      reverse remodeling as LVMI regression and was predictive of this outcome. As a
      simple and practical method, tissue tracking is promising to assess strain and
      predict reverse remodeling in severe AS, especially in patients with suboptimal
      Echo image quality.

PMID- 29061185
TI  - The Community Navigator Study: a feasibility randomised controlled trial of an
      intervention to increase community connections and reduce loneliness for people
      with complex anxiety or depression.
AB  - BACKGROUND: Loneliness is associated with poor health outcomes at all ages,
      including shorter life expectancy and greater risk of developing depression.
      People with mental health problems are particularly vulnerable to loneliness and,
      for those with anxiety or depression, loneliness is associated with poorer
      outcomes. Interventions which support people to utilise existing networks and
      access new social contact are advocated in policy but there is little evidence
      regarding their effectiveness. People with mental health problems have potential
      to benefit from interventions to reduce loneliness, but evidence is needed
      regarding their feasibility, acceptability and outcomes. An intervention to
      reduce loneliness for people with anxiety or depression treated in secondary
      mental health services was developed for this study, which will test the
      feasibility and acceptability of delivering and evaluating it through a
      randomised controlled trial. METHODS: In this feasibility trial, 40 participants
      with anxiety or depression will be recruited through two secondary mental health
      services in London and randomised to an intervention (n = 30) or control group (n
      = 10). The control group will receive standard care and written information about
      local community resources. The coproduced intervention, developed in this study,
      includes up to ten sessions with a 'Community Navigator' over a 6-month period.
      Community Navigators will work with people individually to increase involvement
      in social activities, with the aim of reducing feelings of loneliness. Data will
      be collected at baseline and at 6-month follow-up - the end of the intervention
      period. The acceptability of the intervention and feasibility of participant
      recruitment and retention will be assessed. Potential primary and secondary
      outcomes for a future definitive trial will be completed to assess response and
      completeness, including measures of loneliness, depression and anxiety.
      Qualitative interviews with participants, staff and other stakeholders will
      explore experiences of Community Navigator support, the mechanisms by which it
      may have its effects and suggestions for improving the programme. DISCUSSION: Our
      trial will provide preliminary evidence of the feasibility and acceptability of
      Community Navigator support and of trial procedures for testing this. The results
      will inform a future definitive randomised controlled trial of this intervention.
      TRIAL REGISTRATION: ISRCTN10771821 . Registered on 3 April 2017.

PMID- 29061186
TI  - Successful bridge to recovery in fulminant myocarditis using a biventricular
      assist device: a case report.
AB  - BACKGROUND: Fulminant myocarditis is a life-threatening disease, and myocardial
      damage expands the right ventricle as well as the left ventricle in some cases.
      There is a mortality rate of over 40% in patients with fulminant myocarditis who
      need mechanical circulatory support by peripheral venoarterial extracorporeal
      membrane oxygenation. CASE PRESENTATION: We report a case of a 27-year-old
      Japanese woman who was successfully bridged to recovery by using a biventricular
      assist device. She was diagnosed with fulminant myocarditis, and peripheral
      venoarterial extracorporeal membrane oxygenation was established on the same day.
      Her left ventricular ejection fraction rapidly decreased from 40% to 5% in 3 days
      and weaning from venoarterial extracorporeal membrane oxygenation was deemed
      difficult. Therefore, we performed a ventricular assist device implantation on
      day 4. A left ventricular assist device was implanted first. However, adequate
      blood flow did not circulate to the left side of her heart because of right-sided
      heart failure. Thus, an additional implant of a right ventricular assist device
      was performed during the operation. Her left ventricular ejection fraction
      recovered to 50% on day 10. The biventricular assist device was successfully
      removed on day 14. She has not experienced worsening of biventricular function
      during her follow-ups for 4 years. CONCLUSIONS: Ventricular assist device therapy
      should be considered if there is no improvement in cardiac function in patients
      with fulminant myocarditis regardless of several days of support by venoarterial
      extracorporeal membrane oxygenation. A right ventricular assist device should
      always be implemented when necessary because biventricular involvement is not
      uncommon in fulminant myocarditis.

PMID- 29061187
TI  - Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal
      cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3
      cytokine pathway.
AB  - BACKGROUND: Ischemia-reperfusion (IR) affects microRNA (miR) expression and
      causes substantial inflammation. Multiple roles of the tumor suppressor miR-129
      5p in cerebral IR have recently been reported, but its functions in the spinal
      cord are unclear. Here, we investigated the role of miR-129-5p after spinal cord
      IR, particularly in regulating high-mobility group box-1 (HMGB1) and the Toll
      like receptor (TLR)-3 pathway. METHODS: Ischemia was induced via 5-min occlusion
      of the aortic arch. The relationship between miR-129-5p and HMGB1 was elucidated
      via RT-PCR, western blotting, and luciferase assays. The cellular distribution of
      HMGB1 was determined via double immunofluorescence. The effect of miR-129-5p on
      the expression of HMGB1, TLR3, and downstream cytokines was evaluated using
      synthetic miRs, rHMGB1, and the TLR3 agonist Poly(I:C). Blood-spinal cord barrier
      (BSCB) permeability was examined by measuring Evans blue (EB) dye extravasation
      and the water content. RESULTS: The temporal miR-129-5p and HMGB1 expression
      profiles and luciferase assay results indicated that miR-129-5p targeted HMGB1.
      Compared with the Sham group, the IR group had higher HMGB1 immunoreactivity,
      which was primarily distributed in neurons and microglia. Intrathecal injection
      of the miR-129-5p mimic significantly decreased the HMGB1, TLR3, interleukin (IL)
      1beta and tumor necrosis factor (TNF)-alpha levels and the double-labeled cell
      count 48 h post-surgery, whereas rHMGB1 and Poly(I:C) reversed these effects.
      Injection of miR-129-5p mimic preserved motor function and prevented BSCB leakage
      based on increased Basso Mouse Scale scores and decreased EB extravasation and
      water content, whereas injection rHMGB1 and Poly(I:C) aggravated these injuries.
      CONCLUSIONS: Increasing miR-129-5p levels protect against IR by ameliorating
      inflammation-induced neuronal and BCSB damage by inhibiting HMGB1 and TLR3
      associated cytokines.

PMID- 29061188
TI  - Authors' response to comments from Nachman KE et al.
AB  - Authors' response to comments letter to the editor from Nachman KE et al.

PMID- 29061189
TI  - Documentation of the partograph in assessing the progress of labour by health
      care providers in Malawi's South-West zone.
AB  - BACKGROUND: There is some evidence that appropriate use of partograph in
      monitoring the progress of labour could decrease delivery related complications.
      The documentation of parameters of partographs is however, poorly understood. The
      aim of the present study was to determine the extent to which health care workers
      are making use of the partograph in monitoring the progress of labour through
      checking the documentation of the parameters of the partographs. METHODS: A
      hospital-based descriptive study involving retrospective review of partographs
      for births that occurred in 2016 was conducted in Malawi's South-West zone. A
      total of 1070 partographs that were used to monitor labour in two public
      hospitals were reviewed to determine the documentation of the parameters of
      partographs and descriptive statistics were computed using statistical package
      for the social science software version 22.0. RESULTS: Of the total 1070
      partographs reviewed, 58.6% (n = 627) of the partographs had no recording of
      maternal blood pressure and 65.3% (n = 699) of the partographs had no temperature
      documentation. Moulding was not recorded in 25.4% (n = 272) of the partographs,
      foetal heart rate was not recorded in 14.9% (n = 159) of the partographs and
      descent of the foetal head was not recorded in 12.0% (n = 128) of the
      partographs. CONCLUSION: There is poor documentation of vital parameters of the
      partographs. This suggests insufficient monitoring of the progress of labour,
      which may lead to adverse pregnancy outcomes. To improve the accurate
      documentation of parameters of the partograph, there is a need to understand the
      problem and provide tailor-made solutions to address them and ultimately improve
      pregnancy outcomes. In the meantime, in-service refresher courses on partograph
      use to health care workers need to be conducted regularly. Supportive supervision
      to obstetric care providers and regular partograph audit could also improve
      documentation.

PMID- 29061190
TI  - Development of a core outcome set for clinical trials in basal cell carcinoma:
      study protocol for a systematic review of the literature and identification of a
      core outcome set using a Delphi survey.
AB  - BACKGROUND: Basal cell carcinoma is the most common skin cancer worldwide.
      Treatment options include both surgical and topical modalities. Although risk of
      metastasis is low, basal cell carcinoma can be invasive and infiltrate important
      underlying structures such as bone or cartilage. While many clinical trials
      examining therapies for basal cell carcinoma exist, the lack of consensus in
      outcome reporting across all trials poses a concern. Proper evaluation and
      comparison of treatment modalities is challenging. In order to address the
      inconsistencies present, this project aims to determine a core set of outcomes
      which should be evaluated in all clinical trials of basal cell carcinoma.
      METHODS/DESIGN: Outcomes will be extracted over four phases: (1) a systematic
      literature review, (2) patient interviews, (3) other published sources, and (4)
      stakeholder involvement. Potential outcomes will then be examined by the Steering
      Committee, who may add or remove outcomes. The Delphi process will then be
      performed to condense the list of outcomes generated. Two rounds of Delphi
      surveys will be performed with two groups of participants - physicians and
      patients. A consensus meeting with relevant stakeholders will be conducted after
      the Delphi exercise to further select outcomes, taking into account participant
      scores. By the end of the meeting, members will vote and decide on a final
      recommended set of core outcomes. For the duration of the study, we will be in
      collaboration with both the Core Outcome Measures in Effectiveness Trials (COMET)
      initiative and the Cochrane Skin Group - Core Outcome Set Initiative (CSG
      COUSIN). DISCUSSION: This study aims to develop a core outcome set to guide
      assessment in clinical trials on basal cell carcinoma. The end-goal is to improve
      the consistency of outcome reporting and allow proper evaluation of treatment
      effectiveness.

PMID- 29061192
TI  - An unusual complication of the traditional treatment of a closed fracture -
      generalized tetanus: a case report.
AB  - BACKGROUND: Tetanus is a severe infectious disease that can lead to death. The
      clinical manifestations are due to an exotoxin secreted by Clostridium tetani, a
      spore-producing Gram-positive bacillus. The penetration of the germ is made
      through a skin opening, independently of the size of the wound. CASE
      PRESENTATION: A 13-year-old black African boy of the Bantu ethnic group with
      unknown tetanus vaccination status presented to our pediatric emergency room for
      the management of chest and vertebral pains which started a few days after
      traditional treatment by scarification and herbal and leaf ointment. The
      treatment was initiated by a traditional healer and indicated for a closed
      fracture of our patient's left forearm sustained during a fight. The diagnosis of
      generalized tetanus was made on the basis of generalized contractures with
      opisthotonus, trismus, and autonomic nervous system dysfunction. Despite prompt
      intensive care management, he died a few hours after admission. CONCLUSION: This
      case emphasizes the permanent threat of tetanus in our environment especially
      after cultural and traditional acts like scarification that in this specific case
      was for a therapeutic purpose.

PMID- 29061191
TI  - Profiling, clinicopathological correlation and functional validation of specific
      long non-coding RNAs for hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent and
      aggressive malignancies worldwide. Studies seeking to advance the overall
      understanding of lncRNA profiling in HCC remain rare. METHODS: The transcriptomic
      profiling of 12 HCC tissues and paired adjacent normal tissues was determined
      using high-throughput RNA sequencing. Fifty differentially expressed mRNAs (DEGs)
      and lncRNAs (DELs) were validated in 21 paired HCC tissues via quantitative real
      time PCR. The correlation between the expression of DELs and various
      clinicopathological characteristics was analyzed using Student's t-test or linear
      regression. Co-expression networks between DEGs and DELs were constructed through
      Pearson correlation co-efficient and enrichment analysis. Validation of DELs'
      functions including proliferation and migration was performed via loss-of
      function RNAi assays. RESULTS: In this study, we identified 439 DEGs and 214
      DELs, respectively, in HCC. Furthermore, we revealed that multiple DELs,
      including NONHSAT003823, NONHSAT056213, NONHSAT015386 and especially
      NONHSAT122051, were remarkably correlated with tumor cell differentiation, portal
      vein tumor thrombosis, and serum or tissue alpha fetoprotein levels. In addition,
      the co-expression network analysis between DEGs and DELs showed that DELs were
      involved with metabolic, cell cycle, chemical carcinogenesis, and complement and
      coagulation cascade-related pathways. The silencing of the endogenous level of
      NONHSAT122051 or NONHSAT003826 could significantly attenuate the mobility of both
      SK-HEP-1 and SMMC-7721 HCC cells. CONCLUSION: These findings not only add
      knowledge to the understanding of genome-wide transcriptional evaluation of HCC
      but also provide promising targets for the future diagnosis and treatment of HCC.

PMID- 29061193
TI  - Subtotal Parathyroidectomy and Relocation of the Parathyroid Remnant for Renal
      Hyperparathyroidism: modification of a traditional operation.
AB  - BACKGROUND: We describe a modification of the conventional subtotal
      parathyroidectomy operation where the parathyroid gland(s) remnant is
      repositioned with intact vascular supply to a plane superficial to the infrahyoid
      strap muscles and immediately under the skin incision. This technique called
      Subtotal Parathyroidectomy and Remnant Relocation (SPARE) retains all the
      metabolic advantages of the conventional operation with the added advantage of
      easier identification of a recurrent hyperplastic remnant if re-exploration
      becomes necessary. METHODS: In the SPARE technique, four parathyroid glands were
      identified and the quality of each gland and the length of each vascular pedicle
      to the parathyroid glands were assessed. The optimal parathyroid gland was
      relocated to a plane superficial to the strap muscles. The remainder of the
      glands were removed. RESULTS: In total, 30 patients with hyperparathyroidism
      secondary to renal failure (HSRF) underwent parathyroidectomy with the SPARE
      technique. The mean age was 53.1+/-12.5 years and median follow-up was 17.1
      months (range 1-78.9 months). There were no recurrent laryngeal nerve (RLN)
      injuries or hematomas. The pre- and post-operative value for corrected calcium
      and PTH were 158.4+/-109.4 pmol/L and 11.4+/-12.1 pmol/L, respectively (p <
      0.05). Three recurrences were noted (10.0%), with a mean time to recurrence of
      15.3+/-6.6 months. One patient had excision of the remnant parathyroid glands
      performed under local anaesthetic (29 min); one had re-exploration performed
      under general anaesthetic (81 min), and one was managed medically. CONCLUSION: We
      described a novel parathyroidectomy technique for patients with HSRF, which
      provides the advantages of conventional subtotal parathyroidectomy while
      mitigating the challenges of thyroid bed re-exploration when recurrences arise.

PMID- 29061194
TI  - Impact of a community health worker HIV treatment and prevention intervention in
      an HIV hotspot fishing community in Rakai, Uganda (mLAKE): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Effective yet practical strategies are needed to increase engagement
      in HIV treatment and prevention services, particularly in high-HIV-prevalence
      hotspots. We designed a community-based intervention called "Health Scouts" to
      promote uptake and adherence to HIV services in a highly HIV-prevalent fishing
      community in Rakai, Uganda. Using a situated Information, Motivation, and
      Behavioral skills theory framework, the intervention consists of community health
      workers, called Health Scouts, who use motivational interviewing strategies and
      mobile health tools to promote engagement in HIV treatment and prevention
      services. METHODS/DESIGN: The Health Scout intervention is being evaluated
      through a pragmatic, parallel, cluster-randomized controlled trial with an
      allocation ratio of 1:1. The study setting is a single high-HIV-prevalence
      fishing community in Rakai, Uganda divided into 40 contiguous neighborhood
      clusters each containing about 65 households. Twenty clusters received the Health
      Scout Intervention; 20 clusters received standard of care. The Health Scout
      intervention is delivered within the community at the household level, targeting
      all residents aged 15 years or older. The primary programmatic outcomes are self
      reported HIV care, antiretroviral therapy, and male circumcision coverage; the
      primary biologic outcome is population-level HIV viremia prevalence. Follow-up is
      planned for about 3 years. DISCUSSION: HIV treatment and prevention service
      engagement remains suboptimal in HIV hotspots. New, community-based
      implementation approaches are needed. If found to be effective in this trial, the
      Health Scout intervention may be an important component of a comprehensive HIV
      response. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02556957 . Registered on
      20 September 2015.

PMID- 29061196
TI  - Correction to Crowdsourcing to promote HIV testing among MSM in China: study
      protocol for a stepped wedge randomized controlled trial.

PMID- 29061197
TI  - In vivo evaluation of the efficacy of Sophora moorcroftiana alkaloids in
      combination with Bacillus Calmette-Guerin (BCG) treatment for cystic
      echinococcosis in mice.
AB  - Human cystic echinococcosis is a widespread, chronic, endemic, helminthic
      zoonosis caused by larval tapeworms of the species Echinococcus granulosus. At
      present, there is no rational and effective therapy for patients with
      echinococcosis. The present study evaluated whether the combination of alkaloids
      from Sophora moorcroftiana seeds (SMSa2) and Bacillus Calmette-Guerin (BCG) was
      effective in the treatment of experimental echinococcosis. After 20 weeks of
      secondary infection with protoscoleces, mice were randomly allocated to five
      groups and treated for 6 weeks by daily intragastric administration of
      albendazole (ABZ, 100 mg/kg), SMSa2 (100 mg/kg), BCG (abdominal subcutaneous
      injection at 5 * 106 CFU), SMSa2 + BCG (100 mg/kg SMSa2 and 5 * 106 CFU BCG) or
      normal saline (untreated group), respectively. The results indicated a
      significant reduction in the weight of hydatid cysts in the SMSa2 + BCG group
      compared with the untreated, SMSa2 and BCG groups. The rate of inhibition of
      hydatid cyst growth in the SMSa2 + BCG group (76.1%) was obviously increased
      compared with that in the SMSa2 (25.7%) and BCG (26.6%) groups, respectively.
      Compared with the untreated control, the SMSa2 + BCG group showed a non
      significant increase in serum interleukin-4 (IL-4). Furthermore, the serum levels
      of interferon-gamma (IFN-gamma) between the untreated and SMSa2 + BCG groups were
      not statistically different. Therefore, the combination of alkaloids from S.
      moorcroftiana seeds and BCG can reduce cyst burden and is an effective
      therapeutic regimen against echinococcosis.

PMID- 29061195
TI  - Preclinical effects of APOE epsilon4 on cerebrospinal fluid Abeta42
      concentrations.
AB  - BACKGROUND: From earlier studies it is known that the APOE
      epsilon2/epsilon3/epsilon4 polymorphism modulates the concentrations of
      cerebrospinal fluid (CSF) beta-amyloid1-42 (Abeta42) in patients with cognitive
      decline due to Alzheimer's disease (AD), as well as in cognitively healthy
      controls. Here, in a large cohort consisting solely of cognitively healthy
      individuals, we aimed to evaluate how the effect of APOE on CSF Abeta42 varies by
      age, to understand the association between APOE and the onset of preclinical AD.
      METHODS: APOE genotype and CSF Abeta42 concentration were determined in a cohort
      comprising 716 cognitively healthy individuals aged 17-99 from nine different
      clinical research centers. RESULTS: CSF concentrations of Abeta42 were lower in
      APOE epsilon4 carriers than in noncarriers in a gene dose-dependent manner. The
      effect of APOE epsilon4 on CSF Abeta42 was age dependent. The age at which CSF
      Abeta42 concentrations started to decrease was estimated at 50 years in APOE
      epsilon4-negative individuals and 43 years in heterozygous APOE epsilon4
      carriers. Homozygous APOE epsilon4 carriers showed a steady decline in CSF
      Abeta42 concentrations with increasing age throughout the examined age span.
      CONCLUSIONS: People possessing the APOE epsilon4 allele start to show a decrease
      in CSF Abeta42 concentration almost a decade before APOE epsilon4 noncarriers
      already in early middle age. Homozygous APOE epsilon4 carriers might deposit
      Abeta42 throughout the examined age span. These results suggest that there is an
      APOE epsilon4-dependent period of early alterations in amyloid homeostasis, when
      amyloid slowly accumulates, that several years later, together with other
      downstream pathological events such as tau pathology, translates into cognitive
      decline.

PMID- 29061199
TI  - Sulfur fertilization increases defense metabolites and nitrogen but decreases
      plant resistance against a host-specific insect.
AB  - We tested the sulfur-modulated plant resistance hypothesis using potted cabbage
      (Brassica oleracea var. capitata) plants that were grown without and with
      increasing levels of sulfur fertilization. Changes in plant chemical traits were
      assessed and developmental performance of Plutella xylostella, a highly host
      specific leaf-chewing insect, was followed. Leaf sulfur concentration gradually
      increased with growing addition of sulfur in soil; however, there was a
      generalized saturation response curve, with a plateau phase, for improvements in
      total leaf nitrogen, defense glucosinolates and insect performance. Plutella
      xylostella performed better in sulfur-fertilized cabbage probably because of the
      higher level of nitrogen, despite of the higher content of glucosinolates, which
      are toxic for many non-specialized insects. Despite the importance of sulfur in
      plant nutrition and production, especially for Brassica crops, our results showed
      that sulfur fertilization could decrease plant resistance against insects with
      high feeding specialization.

PMID- 29061198
TI  - Biochemical responses induced in galls of three Cynipidae species in oak trees.
AB  - Gall-making Cynipidae manipulate the leaves of host plant to form galls where
      offspring find shelter and food. The relationship between oak gallwasp and
      biochemical mechanisms of galls still requires a better understanding. So, in
      this research, protein and phenolic compound contents, as well as the activity of
      antioxidative enzymes and pathogenesis-related (PR) proteins were determined.
      Galls caused by asexual generation of Cynips quercusfolii L., Neuroterus
      numismalis (Fourc.) and N. quercusbaccarum L., as a model were used. All cynipid
      species modified the protein levels of gall tissues, but they cannot be treated
      as protein sinks. Significantly higher levels of phenols were observed in the
      galled leaves and galls of all cynipid species when compared with the control
      tissues. Peroxidase and polyphenol oxidase activity was usually low or showed no
      activity in galled tissues of all species. PR proteins, such as chitinase and
      beta-1,3-glucanase, had a similar activity profile. Their activity significantly
      increased in the leaves with galls of all cynipid species, especially those
      infested with C. quercusfolii. Data generated in this study clearly indicate that
      galling Cynipidae manipulate the biochemical machinery of the galls for their own
      needs. However, the pattern of the biochemical features of leaves with galls and
      galled tissues depends on gall-making species.

PMID- 29061200
TI  - A neuropsychiatric case report: Kluver-Bucy and Gastaut-Geschwind syndromes in
      one patient with schizoaffective disorder presenting with brain 99-mTc HMPAO
      single-photon emission computed tomography showing bilateral discrete decrease of
      temporal lobes perfusion.

PMID- 29061201
TI  - Provider Role in Transmission of Carbapenem-Resistant Enterobacteriaceae.
AB  - OBJECTIVE We sought to evaluate the role healthcare providers play in carbapenem
      resistant Enterobacteriaceae (CRE) acquisition among hospitalized patients.
      DESIGN A 1:4 case-control study with incidence density sampling. SETTING Academic
      healthcare center with regular CRE perirectal screening in high-risk units.
      PATIENTS We included case patients with >=1 negative CRE test followed by
      positive culture with a length of stay (LOS) >9 days. For controls, we included
      patients with >=2 negative CRE tests and assignment to the same unit set as case
      patients with a LOS >9 days. METHODS Controls were time-matched to each case
      patient. Case exposure was evaluated between days 2 and 9 before positive culture
      and control evaluation was based on maximizing overlap with the case window.
      Exposure sources were all CRE-colonized or -infected patients. Nonphysician
      providers were compared between study patients and sources during their
      evaluation windows. Dichotomous and continuous exposures were developed from the
      number of source-shared providers and were used in univariate and multivariate
      regression. RESULTS In total, 121 cases and 484 controls were included.
      Multivariate analysis showed odds of dichotomous exposure (>=1 source-shared
      provider) of 2.27 (95% confidence interval [CI], 1.25-4.15; P=.006) for case
      patients compared to controls. Multivariate continuous exposure showed odds of
      1.02 (95% CI, 1.01-1.03; P=.009) for case patients compared to controls.
      CONCLUSIONS Patients who acquire CRE during hospitalization are more likely to
      receive care from a provider caring for a patient with CRE than those patients
      who do not acquire CRE. These data support the importance of hand hygiene and
      cohorting measures for CRE patients to reduce transmission risk. Infect Control
      Hosp Epidemiol 2017;38:1329-1334.

PMID- 29061203
TI  - Exploring perceptions of the Mexican sugar-sweetened beverage tax among
      adolescents in north-west Mexico: a qualitative study.
AB  - OBJECTIVE: To explore awareness and perceptions of the sugar-sweetened beverage
      (SSB) tax implemented in Mexico in 2014 among a sample of Mexican adolescents,
      and to investigate how the tax has affected their purchases and intake of SSB.
      DESIGN: Qualitative. SETTING: Semi-structured interviews were conducted in April
      May 2016. The data were analysed using thematic analysis. SUBJECTS: Adolescents
      residing in north-west Mexico (n 29, 55.2 % females), aged 15-19 years. RESULTS:
      Four main themes emerged: awareness of taxation; perceptions of how the tax has
      affected SSB intake; reasons why the tax was not perceived to have affected SSB
      intake; and preferences for substitution of the taxed SSB. Participants were
      mostly unaware of the tax and perceived that it would not cause reductions in
      their intake of SSB; they felt that the price increase was low and insufficient
      to affect intake. Taste preferences and 'addiction' to SSB were highlighted as
      the main reasons why participants perceived taxation would not affect intake. If
      SSB prices were to increase further via a higher tax, participants would consider
      substituting SSB with other beverages, namely home-made drinks (e.g. 100 % fruit
      juices), non-caloric, instant-flavoured drinks and water. CONCLUSIONS: These
      findings provide important insights into the views of this sample of Mexican
      adolescents regarding the taxation of SSB, by pointing out several possible
      limitations of the tax policy in Mexico. These results could inform the design of
      future interventions directed at Mexican youth that would complement and
      strengthen the current SSB taxation.

PMID- 29061202
TI  - Novel hemotropic mycoplasmas are widespread and genetically diverse in vampire
      bats.
AB  - Bats (Order: Chiroptera) have been widely studied as reservoir hosts for viruses
      of concern for human and animal health. However, whether bats are equally
      competent hosts of non-viral pathogens such as bacteria remains an important open
      question. Here, we surveyed blood and saliva samples of vampire bats from Peru
      and Belize for hemotropic Mycoplasma spp. (hemoplasmas), bacteria that can cause
      inapparent infection or anemia in hosts. 16S rRNA gene amplification of blood
      showed 67% (150/223) of common vampire bats (Desmodus rotundus) were infected by
      hemoplasmas. Sequencing of the 16S rRNA gene amplicons revealed three novel
      genotypes that were phylogenetically related but not identical to hemoplasmas
      described from other (non-vampire) bat species, rodents, humans, and non-human
      primates. Hemoplasma prevalence in vampire bats was highest in non-reproductive
      and young individuals, did not differ by country, and was relatively stable over
      time (i.e., endemic). Metagenomics from pooled D. rotundus saliva from Peru
      detected non-hemotropic Mycoplasma species and hemoplasma genotypes
      phylogenetically similar to those identified in blood, providing indirect
      evidence for potential direct transmission of hemoplasmas through biting or
      social contacts. This study demonstrates vampire bats host several novel
      hemoplasmas and sheds light on risk factors for infection and basic transmission
      routes. Given the high frequency of direct contacts that arise when vampire bats
      feed on humans, domestic animals, and wildlife, the potential of these bacteria
      to be transmitted between species should be investigated in future work.

PMID- 29061205
TI  - Community-based distribution of iron-folic acid supplementation in low- and
      middle-income countries: a review of evidence and programme implications.
AB  - OBJECTIVE: The present literature review aimed to review the evidence for
      community-based distribution (CBD) of iron-folic acid (IFA) supplementation as a
      feasible approach to improve anaemia rates in low- and middle-income countries.
      DESIGN: The literature review included peer-reviewed studies and grey literature
      from PubMed, Cochrane Library, LILAC and Scopus databases. SETTING: Low- and
      middle-income countries. SUBJECTS: Non-pregnant women, pregnant women, and girls.
      RESULTS: CBD programmes had moderate success with midwives and community health
      workers (CHW) who counselled on health benefits and compliance with IFA
      supplementation. CHW were more likely to identify and reach a greater number of
      women earlier in pregnancy, as women tended to present late to antenatal care.
      CBD channels had greater consistency in terms of adequate supplies of IFA in
      comparison to clinics and vendors, who faced stock outages. Targeting women of
      reproductive age through school and community settings showed high compliance and
      demonstrated reductions in anaemia. CONCLUSIONS: CBD of IFA supplementation can
      be a valuable platform for improving knowledge about anaemia, addressing
      compliance and temporary side-effects of IFA supplements, and increasing access
      and coverage of IFA supplementation. Programmatic efforts focusing on community
      based platforms should complement services and information provided at the health
      facility level. Provision of training and supportive supervision for CHW on how
      to counsel women on benefits, side-effects, and when, why, and how to take IFA
      supplements, as part of behaviour change communication, can be strengthened,
      alongside logistics and supply systems to ensure consistent supplies of IFA
      tablets at both the facility and community levels.

PMID- 29061204
TI  - A spatial and temporal analysis of paediatric central nervous system infections
      from 2005 to 2015 in Ho Chi Minh City, Vietnam.
AB  - Central nervous system infections (CNSI) are a leading cause of death and long
      term disability in children. Using ICD-10 data from 2005 to 2015 from three
      central hospitals in Ho Chi Minh City (HCMC), Vietnam, we exploited generalized
      additive mixed models (GAMM) to examine the spatial-temporal distribution and
      spatial and climatic risk factors of paediatric CNSI, excluding tuberculous
      meningitis, in this setting. From 2005 to 2015, there were 9469 cases of
      paediatric CNSI; 33% were ?1 year old at admission and were mainly diagnosed with
      presumed bacterial CNSI (BI) (79%), the remainder were >1 year old and mainly
      diagnosed with presumed non-bacterial CNSI (non-BI) (59%). The urban districts of
      HCMC in proximity to the hospitals as well as some outer districts had the
      highest incidences of BI and non-BI; BI incidence was higher in the dry season.
      Monthly BI incidence exhibited a significant decreasing trend over the study.
      Both BI and non-BI were significantly associated with lags in monthly average
      temperature, rainfall, and river water level. Our findings add new insights into
      this important group of infections in Vietnam, and highlight where resources for
      the prevention and control of paediatric CNSI should be allocated.

PMID- 29061206
TI  - Regional population differences of the brown planthopper (Nilaparvata lugens
      Stal) in Cambodia using genotyping-by-sequencing.
AB  - The brown planthopper Nilaparvata lugens Stal (BPH) can be found year-round in
      tropical region and causes severe damage to rice. Although there has been
      documented BPH damage to rice crops in the past decade in Cambodia, the extent of
      this epidemic is poorly understood. Here, we examined the time variation of BPH
      population in the abundance of morphotypes in 13 main rice-producing provinces
      (86 sites) by aspirator method and in the Takeo Province (five sites) by yellow
      sticky trap method. At least three generations were observed during the 3-month
      collection period in the rainy growing season. Regarding the occurrence of BPH
      morphotypes, in July the macropterous adults were restricted to south Cambodia
      and in August all morphotypes, adults (macropterous and brachypterous) and
      nymphs, appeared in all sampling sites. To explain the difference of regional
      distribution, the genetic differentiation was analyzed in south and northwest
      Cambodia (three sites) by using single nucleotide polymorphisms (SNP) analysis
      via genotyping-by-sequencing (GBS) using next-generation sequencing. The 2455
      SNPs obtained by GBS clarified the three sub-populations and they corresponded to
      the expected dissemination patterns. These results provide a clue to understand
      the differentiation and epidemic of BPH in Cambodia.

PMID- 29061207
TI  - Sales of healthy snacks and beverages following the implementation of healthy
      vending standards in City of Philadelphia vending machines.
AB  - OBJECTIVE: We examined outcomes following the implementation of employer-wide
      vending standards, designed to increase healthy snack and beverage options, on
      the proportion of healthy v. less healthy sales, sales volume and revenue for
      snack and beverage vending machines. DESIGN: A single-arm evaluation of a policy
      utilizing monthly sales volume and revenue data provided by the contracted vendor
      during baseline, machine conversion and post-conversion time periods. Study time
      periods are full calendar years unless otherwise noted. SETTING: Property owned
      or leased by the City of Philadelphia, USA. SUBJECTS: Approximately 250 vending
      machines over a 4-year period (2010-2013). RESULTS: At post-conversion, the
      proportion of sales attributable to healthy items was 40 % for snacks and 46 %
      for beverages. Healthy snack sales were 323 % higher (38.4 to 162.5 items sold
      per machine per month) and total snack sales were 17 % lower (486.8 to 402.1
      items sold per machine per month). Healthy beverage sales were 33 % higher (68.2
      to 90.6 items sold per machine per month) and there was no significant change in
      total beverage sales (213.2 to 209.6 items sold per machine per month). Revenue
      was 11 % lower for snacks ($US 468.30 to $US 415.70 per machine per month) and 21
      % lower for beverages ($US 344.00 to $US 270.70 per machine per month).
      CONCLUSIONS: Sales of healthy vending items were significantly higher following
      the implementation of employer-wide vending standards for snack and beverage
      vending machines. Entities receiving revenue-based commission payments from
      vending machines should employ strategies to minimize potential revenue losses.

PMID- 29061208
TI  - Retrospective, epidemiological cluster analysis of the Middle East respiratory
      syndrome coronavirus (MERS-CoV) epidemic using open source data.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a novel
      coronavirus discovered in 2012. Since then, 1806 cases, including 564 deaths,
      have been reported by the Kingdom of Saudi Arabia (KSA) and affected countries as
      of 1 June 2016. Previous literature attributed increases in MERS-CoV transmission
      to camel breeding season as camels are likely the reservoir for the virus.
      However, this literature review and subsequent analysis indicate a lack of
      seasonality. A retrospective, epidemiological cluster analysis was conducted to
      investigate increases in MERS-CoV transmission and reports of household and
      nosocomial clusters. Cases were verified and associations between cases were
      substantiated through an extensive literature review and the Armed Forces Health
      Surveillance Branch's Tiered Source Classification System. A total of 51 clusters
      were identified, primarily nosocomial (80.4%) and most occurred in KSA (45.1%).
      Clusters corresponded temporally with the majority of periods of greatest
      incidence, suggesting a strong correlation between nosocomial transmission and
      notable increases in cases.

PMID- 29061210
TI  - Penalized classification for optimal statistical selection of markers from high
      throughput genotyping: application in sheep breeds.
AB  - The identification of individuals' breed of origin has several practical
      applications in livestock and is useful in different biological contexts such as
      conservation genetics, breeding and authentication of animal products. In this
      paper, penalized multinomial regression was applied to identify the minimum
      number of single nucleotide polymorphisms (SNPs) from high-throughput genotyping
      data for individual assignment to dairy sheep breeds reared in Sicily. The
      combined use of penalized multinomial regression and stability selection reduced
      the number of SNPs required to 48. A final validation step on an independent
      population was carried out obtaining 100% correctly classified individuals. The
      results using independent analysis, such as admixture, F st, principal component
      analysis and random forest, confirmed the ability of these methods in selecting
      distinctive markers. The identified SNPs may constitute a starting point for the
      development of a SNP based identification test as a tool for breed assignment and
      traceability of animal products.

PMID- 29061209
TI  - Supplementation of Merino ewes with vitamin E plus selenium increases alpha
      tocopherol and selenium concentrations in plasma of the lamb but does not improve
      their immune function.
AB  - Vitamin E and selenium have been reported to improve immune function across a
      range of species. Ewes lambing on poor-quality dry pasture in autumn in Western
      Australia are at risk of being deficient in vitamin E and selenium at lambing
      thus predisposing their lambs to deficiencies and increasing the risk of
      infection and disease. This study tested the hypotheses that (i) supplementation
      of autumn-lambing ewes with vitamin E plus selenium in late gestation will
      increase the concentrations of vitamin E and selenium in plasma in the ewe and
      lamb and (ii) that the increased concentrations of vitamin E and selenium in
      plasma in the lambs will improve their innate and adaptive immune responses and
      thus survival. Pregnant Merino ewes were divided into a control group (n=58)
      which received no supplementation or a group supplemented with vitamin E plus
      selenium (n=55). On days 111, 125 and 140 of pregnancy ewes in the vitamin E plus
      selenium group were given 4 g all-rac-alpha-tocopherol acetate orally. On day 111
      the ewes were also given 60 mg of selenium as barium selenate by subcutaneous
      injection. The concentrations of alpha-tocopherol and selenium were measured in
      ewes and/or lambs from day 111 of pregnancy to 14 weeks of age+/-10 days
      (weaning). Immune function of the lamb was assessed by analysing the numbers and
      phagocytic capacities of monocytes and polymorphonuclear leucocytes and plasma
      IgG and anti-tetanus toxoid antibody concentrations between birth and 14 weeks of
      age+/-10 days. Maternal supplementation with vitamin E plus selenium increased
      the concentration of alpha-tocopherol in plasma (1.13 v. 0.67 mg/l; P<0.001) and
      selenium in whole blood (0.12 v. 0.07 mg/l; P<0.01) of the ewes at lambing
      compared with controls. Supplementation also increased the concentration of alpha
      tocopherol (0.14 v. 0.08 mg/l; P<0.001) and selenium (0.08 v. 0.05 mg/l; P<0.01)
      in lambs at birth compared with controls. There was no significant effect of
      supplementation on immune function or survival in the lambs.

PMID- 29061211
TI  - Viscosity negatively affects the nutritional value of blue lupin seeds for
      broilers.
AB  - This study examines the impact of Lupinus angustifolius variety (C) and inclusion
      level (L) in broiler diets on the nutritional value, viscosity of ileal digesta
      and activity of gut microbiota. The experiment was conducted on 154 female 21-day
      old broilers, allocated to 11 groups (kept individually). A reference lupin-free
      diet and 10 test diets containing one of five lupin seeds; Kadryl, Regent,
      Dalbor, Bojar and Tango, mixed with the reference diet at a ratio of 25 : 75 or
      32 : 68 dry matter (DM) (low or high level of inclusion) were prepared. Diets
      were fed for 6 days, excreta were collected over last 4 days. Apparent
      metabolizable energy corrected to zero N balance (AMEN) of diets and AMEN of
      lupin seeds were calculated. Birds were sacrificed, ileal and caecal digesta were
      pooled by segments from two birds, and the activity of bacterial enzymes was
      determined. The ileal digesta viscosity was measured immediately (ileal viscosity
      immediate (IVI)) or after 6 days storage at -18 degrees C (ileal viscosity
      frozen). AMEN of test diets were lower than the reference diet. Lupin AMEN values
      ranged from 6.04 MJ/kg DM for Regent at high level to 9.25 MJ/kg DM for Bojar at
      low level. High inclusion level numerically decreased AMEN value in all
      cultivars, except for Kadryl, for which it increased (significant C*L
      interaction). The IVI value was 2.6 mPa.s in the reference group, but ranged from
      6.3 to 21.7 mPa.s in lupin-fed birds. It increased significantly with level for
      Regent, Dalbor and Tango but not for the other two cultivars (significant C*L
      interaction). There was a negative correlation between IVI and: apparent total
      tract N retention, fat digestibility from test diets, AMEN of diets and lupins.
      Ileal viscosity immediate was positively correlated with the activity of ileal
      alpha- and beta-glucosidase and negatively with ileal alpha-galactosidase and
      caecal alpha-glucosidase. Ileal viscosity frozen ranged from 3.2 to 5 mPa.s and
      it was not correlated with lupins AMEN. This suggests that the digesta viscosity
      caused by narrow-leafed lupin is detrimental to its nutritional value and
      interfere with the gut microbial activity. In addition, the lupins viscosity was
      measured by two in vitro methods: the water extract viscosity (WEV) method and
      after incubation in conditions imitating in vivo digestion (enzyme-treated
      extract viscosity (EEV)). In vivo viscosity was weakly reflected by in vitro
      measurements as there was no correlation between IVI and WEV or EEV. Overall,
      findings suggest that the different cultivars of narrow-leafed lupin may have
      different value for practical application in broiler diets.

PMID- 29061212
TI  - [Current Status of Prevention and Nursing on Venous Thromboembolism among
      Perioperative Patients with Lung Cancer].
AB  - BACKGROUND: The purpose of this study was to explore the status of prevention and
      nursing on venous thromboembolism (VTE) among perioperative patients with lung
      cancer in Chinese hospital. METHODS: A self-designed questionnaire was used to
      investigate 108 head nurses from tertiary hospitals during the first West China
      Forum on Chest Enhanced Recovery After Surgery (ERAS). RESULTS: (1) Current
      status of assessment tools and prevention guidelines: 97.22% of the hospitals
      have carried out VTE risk assessments for surgical patients with lung cancer,
      67.59% of the hospitals have established the nursing prevention specifications of
      VTE. (2) Current status of screening, precaution and follow-up: 56.48% of the
      hospitals have taken different approach to screen VTE for lung cancer patients in
      pre-operative period. 90.74% of the hospitals and 52.78% of the hospitals had VTE
      prophylaxis for hospitalized and discharged patients, but only 17.59% of
      hospitals were followed up on the incidence of VTE for discharged patients. (3)
      There was no statistically significant difference in VTE prevention between
      different type hospitals (P>0.05). But, all patients in the specialist hospital
      have been fully implemented on VTE risk assessment and VTE prevention (100.00%).
      CONCLUSIONS: The clinical staff have already realized the importance of VTE
      prevention, and the VTE prevention in perioperative patients with lung cancer has
      received extensive attention. But there is still lack of effective risk
      assessment tools and standardized guidelines of VTE prevention.

PMID- 29061213
TI  - [Clinical and Prognosic Anylasis of 30 Cases with Double Primary Lung Cancer].
AB  - BACKGROUND: Multiple primary lung cancer (MPLC) represents a rare variety of
      pulmonary malignant tumor while mainly consist of double primary lung cancer
      (DPLC), but the development of diagnostic techniques promotes the rate diagnosis
      of it in recent years. Here we summarize and anylasis the data of 30 cases with
      DPLC in expectation of improving congnitive of MPLC. METHODS: We retrospectly
      studied 30 MPLC patients who diagnosed from January 2010 to December 2015 in
      Affiliated Cancer Hospital of Zhengzhou University. The clinical characteristics,
      diagnosis, therapeutic methods and prognosis were analyzed. RESULTS: Among 30
      patients enrolled, metachronous DPLC (27/30, 90%) is far more common than
      synchronous DPLC. The majority of the lesions located at right upper lobe (20/60,
      33.3%), and adenocarcinoma (25/60, 41.7%) turns out to be the major pathological
      patter. Patients with same pathological pattern of two lesions of DPLC (17/30,
      56.7%) were slightly more than those with different pattern (13/30, 43.3%) and
      adeno-adeno was the most common pattern in the former ones. Cox regression
      anylasis shows that lymphatic metastasis (HR=4.349, 95%CI: 1.435-13.178, P=0.009)
      and experience of heavy smoking (HR=2.996, 95%CI: 1.089-8.240, P=0.034) were
      associate with worse prognosis. CONCLUSIONS: DPLC are mainly located at right
      upper lobe, and mostly adenocarcinomas. Earlier diagnosis, active therapeutic
      approaches and a strict smoking cessation strategy may improve the prognosis of
      MPLC.

PMID- 29061214
TI  - [Long-term Efficacy of Radiofrequency Ablation Combined with Chemotherapy ?in the
      Treatment of Patients with Advanced Non-small Cell Lung Cancer?--A Retrospective
      Study].
AB  - BACKGROUND: Radiofrequency ablation (RFA) combined with chemotherapy has a
      certain short-term therapeutic effect for the treatment of advanced non-small
      cell lung cancer (NSCLC), but whether it can improve the long-term survival rate
      of patients is still controversy. This study retrospectively analyzed the
      difference of long-term efficacy between RFA combined with chemotherapy and
      chemotherapy alone in the treatment of patients with advanced NSCLC. METHODS: A
      total of 77 patients with stage IIIb and stage IV NSCLC who underwent
      radiofrequency ablation and chemotherapy in the Department of Thoracic Surgery,
      Xuanwu Hospital, Capital University of Medical Sciences from September 2009 to
      December 2015 were enrolled as the treatment group. Chemotherapy with no
      radiofrequency ablation was performed in 56 patients with stage IIIb and stage IV
      NSCLC as the control group. Two groups of patients were followed up by telephone
      about their living conditions. "Survival" package of R software version 3.4.1 was
      used for statistical analysis. Two sets of data baseline levels were tested by
      chi-square test. The bias was processed by Cox regression model and the survival
      curve was plotted using covariate mean substitution method. RESULTS: The first
      year survival rate of the treatment group was 70.74%, the two-year survival rate
      was 39.31% and the median survival time was 22.1 months. The one-year survival
      rate was 54.54% in the control group, the two-year survival rate was 19.49%, the
      median survival for 18.1 months. The long-term survival rate of the treatment
      group was better than that of the control group (P<0.05, OR=0.571). CONCLUSIONS:
      Radiofrequency ablation of lung cancer combined with chemotherapy can
      significantly improve the 2-year survival rate of patients with stage IIIb and
      stage IV NSCLC.

PMID- 29061215
TI  - [Relationship between MTA1 Expression and Prognosis of Chinese Lung Cancer
      ?Patients: A Meta-analysis].
AB  - BACKGROUND: It has been proven that metastasis associated protein 1 (MTA1) was
      correlated with tumor invasion and migration and poor prognosis of several
      malignant carcinomas. The prognostic role of MTA1 expression in lung cancer
      remained controversial, we performed this meta-analysis to assess the prognostic
      value of MTA1 expression in lung cancer. METHODS: A systematic literature search
      was conducted to identify eligible studies which dealing with the relationship
      between MTA1 expression and prognosis of lung cancer in PubMed, Embase, Wanfang
      databases, China Biology Medicine disc and China National Knowledge
      Infrastructure. The pooled hazard ratio (HR) were used to assess the relationship
      between MTA1 expression and prognosis of lung cancer. All data were analysed
      using the Stata 12.0 software. RESULTS: A total of 712 Chinese lung cancer
      patients from 8 studies were included in this meta-analysis. There was
      significant heterogeneity existed in these studies (I2=59.0%, P=0.017), so we
      used a random effects model to calculate the pooled HR=2.07 (95%CI: 1.42-3.02,
      P<0.001). At the same time, we observed through stratified analysis by histology
      that there was no significant heterogeneity in non-small cell lung cancer
      (NSCLC), and the fixed effects model was used to calculate the pooled HR=1.66
      (95%CI: 1.27-2.18, P<0.001). CONCLUSIONS: Overexpression of MTA1 could be a
      marker of poor prognosis in Chinese NSCLC patients, but not in lung cancer or
      small cell lung cancer. Additional studies with larger samples and well-designed
      were required to derive the more precise outcome.

PMID- 29061216
TI  - [Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients
      with Advanced Lung Adenocarcinoma].
AB  - BACKGROUND: Among frequently-used tumor markers in lung cancer, carcinoembryonic
      antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1)
      and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro
      gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung
      adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing
      patients with multiple increased tumor markers (group A) and patients with
      increase of CEA and/or CA125 (group B), this study aims to investigate the
      utility of multiple increased tumor markers in therapeutic evaluation and
      prediction of disease relapsing in patients with advanced lung adenocarcinoma.
      METHODS: Patients with stage IV lung adenocarcinoma who receiving the first line
      chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were
      enrolled and retrospectively analyzed. Clinical characteristic, serum tumor
      markers before chemotherapy, efficacy evaluation, progression-free survival (PFS)
      were analyzed. RESULTS: Except CEA and CA125, the highest ratio of increased
      tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and
      ProGRP (12%). Patients with multiple increased tumor markers tend to have more
      distant metastasis (P<0.001) and shorter PFS (median PFS 5.3 months vs 7.3
      months, P=0.016). The relapse risk was lower in patients who accepted maintenance
      therapy than those who didn't accept maintenance therapy in both groups
      (P<0.001). CONCLUSIONS: Patients with multiple increased tumor markers have high
      risk of relapse, and maintenance therapy can reduce relapse risk.

PMID- 29061217
TI  - [A Reflection of the New Wave of Immunotherapy on the Clinical Study of ?Chinese
      Lung Cancer Immunotherapy].
AB  - Starting from the success of anti-CTLA-4 antibody in malignant melanoma, targeted
      immunotherapy has become one of the effective strategies for anti-tumor therapy,
      and raised a new wave of research on tumor immunotherapy. In the field of lung
      cancer, a series of clinical studies on immune-targeted drugs have been carried
      out aboard, nivolumab, pembrolizumab and atezolizumab have been approved for the
      treatment of lung cancer, which rewrite the history of lung cancer treatment. In
      China, clinical studies on immune-targeted drugs for lung cancer have also been
      developed. The present study mainly analyzed and investigated the current
      situation, gap and future innovation of the research on anti-tumor immunity of
      lung cancer in China.

PMID- 29061218
TI  - [Research Progresses of Circulating Tumor Cells in Diagnosis and Treatment of
      ?Early Lung Cancer].
AB  - As one of the important liquid biopsies, circulating tumor cells (CTCs) shows
      more and more clinical values in the treatment of lung cancer such as diagnostic
      screening, treatment evaluation, postoperative monitoring, and prognosis
      predicting etc. A large number of small pulmonary nodules patients are detected
      when screening the high risk population of lung cancer. However, small lung
      nodules are not equal to lung cancer, and 90%-95% of them are benign lesion,
      therefore, to accurately and correctly differentiate whether it is benign or
      malignant when patients firstly detected and treat a small pulmonary nodule is
      become a new opportunity and challenge for clinician. With the improvement of
      CTCs detection technology, whether it will play an important role in early
      differential diagnosis of lung cancer. And whether it will have clinical
      significance to early lung cancer surgery operations. These require further
      researches and explorations so as to achieve clinical transformation in the
      future.

PMID- 29061219
TI  - [Progress of Sublobectomy for the Treatment of Stage I Non-small Cell Lung Cancer
      in the Elderly].
AB  - Lung cancer continues to be one of the leading causes of cancer-related mortality
      worldwide and its incidence is still increasing. With aging population and
      development in imaging technology, many more elderly with early-stage lung
      cancers are being diagnosed than in the past. Lobectomy and sub-lobar resection
      are two main surgical approach for the treatment for this kind of patients. This
      review aimed to compare these two methods for this hot issue.

PMID- 29061220
TI  - [Advances in Patient Derived Tumor Xenograft (PDTX) Model from Lung Cancer].
AB  - With the development of tumor molecular biology and genomics, it has been
      recognized that there are great heterogeneity in the biological characteristics,
      molecular typing and reactivity of the same tumor species among different
      individuals. In order to achieve true tumor individualized and precise therapy, a
      new concept of human tumor tissue xenograft model (patient derived tumor
      xenograft, PDTX) is proposed. The previous study has revealed that PDTX model can
      truly reflect the biological characteristics of tumor tissue and drug efficacy.
      And PDTX model could be used to select individual chemotherapy regime, evaluate
      drug resistance and explore efficacy and safety of new drug. PDTX model has been
      used in clinical practice of several type of cancer including lung cancer. In
      this paper, the current research progress of lung cancer PDTX is reviewed.

PMID- 29061221
TI  - [Advances in the Transformation to Small Cell Lung Cancer from Non-small Cell
      Lung Cancer Following Acquired Drug-resistance to EGFR Tyrosine Kinase
      Inhibitors].
AB  - The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR
      TKIs) in the treatment of sensitive EGFR mutation in non-small cell lung cancer
      (NSCLC) has been proved significant curative effect. However, the acquisition of
      the drug resistance to EGFR-TKIs is almost inevitable, and common drug resistance
      mechanisms include T790M mutation, cMET amplification, etc. One of the rare
      resistance mechanisms of EGFR-TKIs is the transformation from NSCLC into small
      cell lung cancer (SCLC), which account for about 3%-15%. It is an important rare
      drug resistance mechanism which is not well understood. Therefore, it is
      necessary to review the present situation and the progress of the this drug
      resistance mechanism. This article summarizes these hypothesizes from two parts,
      which are respectively the "common origin" and "transformation time node". At
      present, two possible mechanisms of this kind of transformation has been
      proposed, which are respectively the hypothesis of the tumor heterogeneity and
      the hypothesis of the transformation from NSCLC into SCLC. This article also
      involves a lot of changes in the level of molecules, such as the lack of RB1
      gene, the inactivation of P53 gene and the mutation of PTEN M264I gene, etc. At
      the same time, this article summarizes the characteristics, the diagnostic
      methods and the treatment strategy of this kind of transformation. There are
      still many problems which need further research and resolution.

PMID- 29061222
TI  - International multicentre randomised controlled trial of improvisational music
      therapy for children with autism spectrum disorder: TIME-A study.
AB  - BACKGROUND: Preliminary studies have indicated that music therapy may benefit
      children with autism spectrum disorders (ASD). OBJECTIVES: To examine the effects
      of improvisational music therapy (IMT) on social affect and responsiveness of
      children with ASD. DESIGN: International, multicentre, three-arm, single-masked
      randomised controlled trial, including a National Institute for Health Research
      (NIHR)-funded centre that recruited in London and the east of England.
      Randomisation was via a remote service using permuted blocks, stratified by study
      site. SETTING: Schools and private, voluntary and state-funded health-care
      services. PARTICIPANTS: Children aged between 4 and 7 years with a confirmed
      diagnosis of ASD and a parent or guardian who provided written informed consent.
      We excluded children with serious sensory disorder and those who had received
      music therapy within the past 12 months. INTERVENTIONS: All parents and children
      received enhanced standard care (ESC), which involved three 60-minute sessions of
      advice and support in addition to treatment as usual. In addition, they were
      randomised to either one (low-frequency) or three (high-frequency) sessions of
      IMT per week, or to ESC alone, over 5 months in a ratio of 1 : 1 : 2. MAIN
      OUTCOME MEASURES: The primary outcome was measured using the social affect score
      derived from the Autism Diagnostic Observation Schedule (ADOS) at 5 months:
      higher scores indicated greater impairment. Secondary outcomes included social
      affect at 12 months and parent-rated social responsiveness at 5 and 12 months
      (higher scores indicated greater impairment). RESULTS: A total of 364
      participants were randomised between 2011 and 2015. A total of 182 children were
      allocated to IMT (90 to high-frequency sessions and 92 to low-frequency
      sessions), and 182 were allocated to ESC alone. A total of 314 (86.3%) of the
      total sample were followed up at 5 months [165 (90.7%) in the intervention group
      and 149 (81.9%) in the control group]. Among those randomised to IMT, 171 (94.0%)
      received it. From baseline to 5 months, mean scores of ADOS social affect
      decreased from 14.1 to 13.3 in music therapy and from 13.5 to 12.4 in standard
      care [mean difference: music therapy vs. standard care = 0.06, 95% confidence
      interval (CI) -0.70 to 0.81], with no significant difference in improvement.
      There were also no differences in the parent-rated social responsiveness score,
      which decreased from 96.0 to 89.2 in the music therapy group and from 96.1 to
      93.3 in the standard care group over this period (mean difference: music therapy
      vs. standard care = -3.32, 95% CI -7.56 to 0.91). There were seven admissions to
      hospital that were unrelated to the study interventions in the two IMT arms
      compared with 10 unrelated admissions in the ESC group. CONCLUSIONS: Adding IMT
      to the treatment received by children with ASD did not improve social affect or
      parent-assessed social responsiveness. FUTURE WORK: Other methods for delivering
      music-focused interventions for children with ASD should be explored. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN78923965. FUNDING: This project was
      funded by the NIHR Health Technology Assessment programme and will be published
      in full in Health Technology Assessment; Vol. 21, No. 59. See the NIHR Journals
      Library website for further project information.

PMID- 29061223
TI  - Association between donor and recipient Interleukin-18 gene polymorphisms and the
      risk of infection after liver transplantation.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate the
      association between Interleukin-18 (IL-18) gene polymorphisms of the donor and
      recipient in liver transplant patients with bacterial infections. METHODS: Five
      single nucleotide polymorphisms (SNPs) (rs7106524, rs5744247, rs1946518, rs549908
      and rs187238) of the IL-18 gene from the donors were genotyped and their
      association with post-operative bacterial infections was evaluated in liver
      transplant patients (N=113). A second independent group of liver transplant
      patients from a different organ transplant centre was also recruited for
      validation purposes (N=44). RESULTS: IL-18 mRNA mean expression levels and
      protein levels were significantly lower in liver transplant patients with
      bacterial infections. For the donor SNP rs1946518, more recipients carried the A
      allele in the bacterial-infected group than the uninfected group (61.4% vs 39.7%;
      P <=0.002). The mean IL-18 mRNA expression and protein levels were significantly
      lower in the transplanted livers of recipients carrying the rs1946518 AA genotype
      compared with those from recipients with CC genotype (3.64, 3.33 vs. 2.75,
      P<=0.048). The A allele of rs1946518 also resulted in lower luciferase activity
      than the C allele in a reporter assay. The area under ROC curve indicated that
      the rs1946518 SNP genotype in the donor liver predicted an increased risk of
      bacterial infection after liver transplantation (AUROC>0.82). CONCLUSIONS: These
      findings indicate that the IL-18 rs1946518 SNP in the donor liver is a risk
      factor for developing bacterial infection after liver transplantation.

PMID- 29061224
TI  - Glucagon-like peptide-1 levels and dipeptidyl peptidase-4 activity in type 2
      diabetes.
AB  - PURPOSE: Hyperglycemia is the major risk factor for microvascular complications
      in type 2 diabetes mellitus (T2DM) patients. This randomized controlled clinical
      trial aimed to investigate T2DM patients with microvascular complications with
      regard to possible relations among serum clusterin (CLU), amylin, secreted
      frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) and
      dipeptidyl peptidase-4 (DPP-4) activities. METHODS: Subject groups were defined
      as follows: T2DM without complications (n=25, F/M=9/16, age 53.9+/-11.1 years);
      T2DM+Retinopathy (n=25, F/M=13/12, age 63.8+/-7.1 years); T2DM+Nephropathy (n=25,
      F/M=13/12, age 58.7+/-14.4 years); T2DM+Neuropathy (n=25, F/M=15/10, age 63.2+/
      9.6 years); and healthy control subjects (HC) (n=25). CLU, amylin, SFRP-4, DPP-4
      and GLP-1 (total and active) activities were measured and compared in blood
      samples from type 2 diabetic patients with and without microvascular
      complications. RESULTS: Significantly lower levels of DPP-4 and GLP-1total (P.

PMID- 29061225
TI  - Combination of alpha-blocker and 5alpha-reductase inhibitor for treatment of
      benign prostatic hyperplasia.
AB  - PURPOSE: This study compared the efficacy of an alpha-blocker monotherapy alone
      with a combination of alpha-blocker plus 5alpha-reductase in treatment of benign
      prostatic hyperplasia (BPH). METHODS: Medline (PubMed), EMBASE, CENTRAL (Cochrane
      databases) and Google Scholar were searched until May 2015 using the following
      search terms: ([alpha-blocker] AND 5alpha-reductase inhibitor) AND benign
      prostatic hyperplasia; and benign prostatic hyperplasia AND (adrenergic alpha
      blockers OR 5 alpha reductase inhibitor). Randomized controlled trials (RCTs)
      that included men with a clinical diagnosis of BPH were included. Eligible
      studies had to have an intervention group that received combination therapy
      (5alpha reductase inhibitor plus alpha-blocker) and a control group that received
      only alpha-blocker. Quality assessment and sensitivity analysis were performed.
      RESULTS: Six studies were included. Combination therapy was found to
      significantly reduce urinary retention incidence rate (OR=0.286, 95%CI: 0.199 -
      0.412, P.

PMID- 29061226
TI  - Scientific Overview on CSCI-CITAC Annual General Meeting and 2016 Young
      Investigators' Forum.
AB  - The 2016 Annual General Meeting of the Canadian Society of Clinician
      Investigators (CSCI) and Clinician Investigator Trainee Association of
      Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC)
      was a national conference held in Toronto November 21-23, 2016, in conjunction
      with The University of Toronto Clinician Investigator Program Research Day. The
      theme for this year's meeting was "Mapping Your Career as a Clinician-Scientist";
      emphasizing essential skills for developing a fruitful career as clinician
      scientist. The meeting featured an opening presentation by Dr. Alan Underhill,
      Dr. Nicola Jones and Alexandra Kuzyk. The keynote speakers were Dr. Nada Jabado
      (McGill University), who discussed the association between cancer and histones,
      Dr. Norman Rosenblum (University of Toronto), who addressed the career path and
      the "calling" of the Clinician Scientist, Dr. Martin Schmeing (McGill
      University), who was the 2016 Joe Doupe Award recipient, and Dr. Linda Rabeneck
      (Cancer Care Ontario and University of Toronto), who received the Friends of CIHR
      lectureship. The workshops, focusing on career development for clinician
      scientists, were hosted by Drs. Alan Underhill, Nicola Jones, Lynn Raymond,
      Michael Schlossmacher and Norman Rosenblum, as well as University of Toronto
      communication specialists, Caitlin Johannesson and Suzanne Gold. In addition, the
      Young Investigators' Forum included presentations from clinician investigator
      trainees from across the country. The research topics were diverse and
      comprehensive: from basic sciences to clinical practice; from epidemiology to
      medical engineering. All scientific abstracts are summarized in this review. Over
      70 abstracts were showcased at this year's meeting during two poster sessions,
      with six outstanding abstracts selected for oral presentations during the
      President's Forum.

PMID- 29061227
TI  - Building health literacy responsiveness in Melbourne's west: a systems approach.
AB  - With high health inequities among some population groups, health professionals
      and organisations are increasingly taking action on health literacy. This case
      study demonstrates how a systems approach to health literacy responsiveness
      created change across a region. From 2013 to 2017 the Health Literacy Development
      Project incorporating a training course and community of practice (the Project)
      targeted the health and community services system in Melbourne's west. The
      Project created a ripple effect that built health literacy responsiveness at the
      individual and organisational level. This contributed to increased use of health
      literacy practices and led to systems change across the region. Creating change
      within the health and community services system is extremely challenging. This
      case study provides some evidence that a systems approach can support change in
      the health literacy responsiveness of a regional health and community services
      system over a 4-year timeframe.

PMID- 29061229
TI  - Disclosure Matters: Enhancing Patient-Provider Communication is Necessary to
      Improve the Health of Sexual Minority Adolescents.

PMID- 29061230
TI  - Addressing Racial/Ethnic Differences in Age-Related Declines in Physical Activity
      During Adolescence.

PMID- 29061231
TI  - Improving Adolescent Immunization Coverage: The Time to Act Is Now.

PMID- 29061228
TI  - Neural and computational processes underlying dynamic changes in self-esteem.
AB  - Self-esteem is shaped by the appraisals we receive from others. Here, we
      characterize neural and computational mechanisms underlying this form of social
      influence. We introduce a computational model that captures fluctuations in self
      esteem engendered by prediction errors that quantify the difference between
      expected and received social feedback. Using functional MRI, we show these social
      prediction errors correlate with activity in ventral striatum/subgenual anterior
      cingulate cortex, while updates in self-esteem resulting from these errors co
      varied with activity in ventromedial prefrontal cortex (vmPFC). We linked
      computational parameters to psychiatric symptoms using canonical correlation
      analysis to identify an 'interpersonal vulnerability' dimension. Vulnerability
      modulated the expression of prediction error responses in anterior insula and
      insula-vmPFC connectivity during self-esteem updates. Our findings indicate that
      updating of self-evaluative beliefs relies on learning mechanisms akin to those
      used in learning about others. Enhanced insula-vmPFC connectivity during updating
      of those beliefs may represent a marker for psychiatric vulnerability.

PMID- 29061232
TI  - Reports of Postural Orthostatic Tachycardia Syndrome After Human Papillomavirus
      Vaccination in the Vaccine Adverse Event Reporting System.
AB  - PURPOSE: Human papillomavirus (HPV) vaccination prevents infections with HPV
      strains that cause certain cancers. Reports of postural orthostatic tachycardia
      syndrome (POTS) following HPV vaccination have raised safety concerns. We
      reviewed POTS reports submitted to the Vaccine Adverse Event Reporting System
      (VAERS). METHODS: We searched the VAERS database for reports of POTS following
      any type of HPV vaccination (bivalent, quadrivalent, or nonavalent) from June
      2006 to August 2015. We reviewed reports and applied established POTS diagnostic
      criteria. We calculated unadjusted POTS case reporting rates based on HPV vaccine
      doses distributed and conducted empirical Bayesian data mining to screen for
      disproportional reporting of POTS following HPV vaccination. RESULTS: Among
      40,735 VAERS reports following HPV vaccination, we identified 29 POTS reports
      that fully met diagnostic criteria. Of these, 27 (93.1%) were in females and mean
      age was 14 years (range 12-32). Median time from vaccination to start of symptoms
      was 43 days (range 0-407); most (18, 75.0%) had onset between 0 and 90 days.
      Symptoms frequently reported concomitantly included headache (22, 75.9%) and
      dizziness (21, 72.4%). Twenty (68.9%) reports documented a history of pre
      existing medical conditions, of which chronic fatigue (5, 17.2%), asthma (4,
      13.8%), and chronic headache (3, 10.3%) were most common. Approximately one POTS
      case is reported for every 6.5 million HPV vaccine doses distributed in the
      United States. No empirical Bayesian data mining safety signals for POTS and HPV
      vaccination were detected. CONCLUSIONS: POTS is rarely reported following HPV
      vaccination. Our review did not detect any unusual or unexpected reporting
      patterns that would suggest a safety problem.

PMID- 29061234
TI  - The Authors reply.

PMID- 29061233
TI  - Gender Identity and Malnutrition: So Much Remains Unknown.

PMID- 29061236
TI  - Forest Plots: Linear or Logarithmic Scale?

PMID- 29061235
TI  - The Authors reply.

PMID- 29061237
TI  - The Authors reply.

PMID- 29061238
TI  - Primary Angiitis of the Central Nervous System.
AB  - Primary angiitis of the central nervous system (PACNS) is rare but often included
      in the differential diagnosis for unusual or unexplained neurologic symptoms
      owing to its array of clinical manifestations. PACNS is not a single entity, but
      rather an umbrella term for distinct subtypes of disease affecting different
      parts of the CNS, different sized vessels, and with different histologic and
      pathologic findings. Although brain biopsy is considered the gold standard test,
      it is neither highly sensitive nor specific. One must always pursue a workup for
      mimics of PACNS. Treatment consists of prednisone monotherapy or combination
      therapy with prednisone and cyclophosphamide.

PMID- 29061239
TI  - Neurologic Manifestations of Primary Sjogren Syndrome.
AB  - The neurologic manifestations of primary Sjogren syndrome are varied and can be
      divided anatomically into 2 categories: peripheral neuropathies and central
      nervous system (CNS) conditions. Distal sensory and sensorimotor neuropathies are
      the most common manifestations of peripheral nerve disease in primary Sjogren
      syndrome. CNS manifestations associated with primary Sjogren syndrome include
      focal central lesions, conditions that mimic multiple sclerosis, encephalitis,
      aseptic meningitis, cerebellar syndromes, movement disorders, and problems with
      memory, cognition, and depression. The heterogeneity of neurologic manifestations
      in primary Sjogren syndrome complicates the approach to treatment, which should
      be directed toward the underlying neuropathologic mechanism.

PMID- 29061240
TI  - Central Nervous System Manifestations of Systemic Lupus Erythematosus.
AB  - Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a variety of
      phenomena. Manifestations are focal or diffuse, and correlate with disease
      mechanisms. Recent understanding of the contribution of blood-brain barrier
      dysfunction to the passage of circulating antineuronal antibodies into the brain
      parenchyma has shed light on pathogenesis. Correct attribution of
      neuropsychiatric manifestations to SLE remains a challenge, but validated
      attribution models will help. Diagnosis relies on characteristic clinical
      manifestations, SLE disease activity, antibody measurements, cerebrospinal fluid
      findings, specific neuroimaging findings, and exclusion of alternative
      etiologies. Current treatment encompasses the identification and management of
      the inciting event, symptomatic treatment, and anticoagulation or
      immunosuppression.

PMID- 29061241
TI  - Central Nervous System Manifestations of Antiphospholipid Syndrome.
AB  - Neurologic manifestations are common in patients with antiphospholipid antibodies
      and include stroke, seizures, dementia, cognitive dysfunction, chorea, migraine,
      psychosis, and demyelinating disease. Many of these disorders mimic their
      idiopathic counterparts, yet treatment for antiphospholipid antibody-associated
      disease can be quite different compared with treatment of CNS disease not
      associated with these antibodies. For patients with antiphospholipid antibody
      associated neurologic disease, anticoagulation or immunosuppressive therapy or
      both may significantly improve their symptoms. Thus, one should have a high index
      of suspicion for antiphospholipid syndrome in the appropriate clinical context.

PMID- 29061242
TI  - Neurologic Manifestations of Rheumatoid Arthritis.
AB  - Neurologic manifestations of rheumatoid arthritis (RA) range in severity from
      mild paresthesias in the hand from carpal tunnel syndrome to sudden death due to
      impingement of the medulla by an eroded, vertically subluxed dens. Most
      neurologic complications are a consequence of articular inflammation and damage
      that leads to compression of adjacent structures of the central or peripheral
      nervous systems. Rare but serious extra-articular manifestations include
      inflammation of the meninges and ischemic neuropathies due to necrotizing
      arteritis of the vasa vasorum. Medical therapy with synthetic disease-modifying
      antirheumatic drugs and biological agents has diminished the incidence of serious
      neurologic manifestations in RA.

PMID- 29061243
TI  - Central Nervous System Disease in Antineutrophil Cytoplasmic Antibodies
      Associated Vasculitis.
AB  - Central nervous system (CNS) disease is an uncommon but significant complication
      of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and
      affects 3 primary areas of the CNS: the pituitary, the pachymeninges, and the CNS
      vasculature. Pituitary disease in uncommon, but hormonal deficiencies can be long
      lasting even in the face of excellent disease response. Chronic hypertrophic
      pachymeninigitis occurs in anti-proteinase 3-positive patients with systemic GPA
      and in anti-myeloperoxidase-positive patients with a milder and more limited form
      of the disease. Cerebral and spinal vasculitis due to GPA and MPA presents with
      focal and general neurologic abnormalities.

PMID- 29061244
TI  - Neuromyelitis Optica.
AB  - Neuromyelitis optica (NMO), formerly known as Devic disease, is an autoimmune
      astrocytopathic disease characterized by transverse myelitis and optic neuritis.
      Most patients demonstrate a relapsing course with incomplete recovery between
      attacks, resulting in progressive disability. The pathogenesis involves
      production of aquaporin-4 antibodies (AQP4-IgG) by plasmablasts in peripheral
      circulation, disruption of the blood-brain barrier, complement-mediated astrocyte
      injury, and secondary demyelination. The diagnosis relies on characteristic
      clinical manifestations in the presence of serum AQP4-IgG positivity or specific
      neuroimaging findings, and exclusion of alternative etiologies. Current treatment
      involves aggressive immunosuppression with pulse-dose steroids during acute
      attacks and long-term immunosuppression for attack prevention.

PMID- 29061245
TI  - Neurosarcoidosis.
AB  - Neurosarcoidosis occurs in 3% to 10% of patients with sarcoidosis. Cranial
      neuropathy and meningeal involvement are the most common manifestations, but any
      part of the nervous system can be affected. Definite diagnosis requires the
      presence of noncaseating granuloma in the nervous system, although
      histopathologic confirmation is often not obtainable. Moderate to high dose of
      glucocorticoids is the main therapy for neurosarcoidosis. Relapse often occurs
      after the dose of glucocorticoids is tapered down, often necessitating the use of
      steroid-sparing immunosuppressive agents.

PMID- 29061247
TI  - Neurologic Features of Immunoglobulin G4-Related Disease.
AB  - Immunoglobulin G4-related disease (IgG4-RD) can involve nearly any organ system,
      including the central and peripheral nervous systems. IgG4 antibodies are not
      known to play a primary etiologic role in disease. IgG4-RD must be distinguished
      from a growing number of immune-mediated conditions in which IgG4 autoantibodies
      contribute directly to pathophysiology. The most common neurologic features of
      IgG4-RD result from disease in the orbits, pachymeninges, and substance of the
      pituitary gland and stalk, as well as a perineuropathy that can involve
      peripheral or cranial nerves. Disease affecting the brain parenchyma is rare but
      reported.

PMID- 29061248
TI  - Involvement of the Peripheral Nervous System in Polyarteritis Nodosa and
      Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis.
AB  - Peripheral nerve involvement is common in polyarteritis nodosa and the
      antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides. The
      underlying mechanism is arteritis of the vasa nervorum, leading to ischemic
      neuropathy. The classic presentation is stepwise involvement of peripheral nerves
      with ongoing antecedent constitutional symptoms. This article reviews the
      pathologic findings, clinical syndromes, diagnosis, and treatment of ANCA
      associated vasculitides.

PMID- 29061246
TI  - Central Nervous System Infections Associated with Immunosuppressive Therapy for
      Rheumatic Disease.
AB  - Patients on immunosuppressive therapy for rheumatic diseases are at increased
      risk of infection. Although infections of the central nervous system (CNS) are
      less common compared with other sites, patients on broadly immunosuppressive and
      biologic immunomodulatory agents may be susceptible to more severe, disseminated
      forms of infection, including of the CNS. Certain key principles regarding
      infection risk apply across immunosuppressive therapies, including increased risk
      with higher doses and longer duration of therapy and with combination therapy.
      Providers should be aware of the CNS infection risk related to immunosuppressant
      use to help guide best practices for screening and prophylaxis.

PMID- 29061249
TI  - Neurologic Manifestations of Rheumatic Diseases.

PMID- 29061250
TI  - Neurologic Manifestations of Rheumatic Diseases.

PMID- 29061251
TI  - Editorial.

PMID- 29061252
TI  - Reduce noise: Improve the nation's health.

PMID- 29061253
TI  - Engaging communities in creating health: Leveraging community benefit.

PMID- 29061254
TI  - Increasing the capacity of public health nursing to strengthen the public health
      infrastructure and to promote and protect the health of communities and
      populations.

PMID- 29061255
TI  - English Language Proficiency, Hearing Impairment, and Functional Change in Mild
      Cognitive Impairment.

PMID- 29061256
TI  - Optimizing palliation of malignant hilar strictures by the use of endobiliary
      stents.

PMID- 29061257
TI  - Are we ready to move toward digital image interpretation in Barrett's esophagus
      surveillance?

PMID- 29061258
TI  - Reporting progress in ERCP hospital credentialing and quality review: stagnant is
      an understatement.

PMID- 29061259
TI  - Will you be my first colonoscopy patient? Planning simulator training for novice
      endoscopists.

PMID- 29061260
TI  - The rising prevalence of early-onset colorectal cancer: Ready and FIT to tackle?

PMID- 29061261
TI  - Indomethacin and lactated Ringer's hydration to prevent post-ERCP pancreatitis:
      right combination but wrong volume.

PMID- 29061262
TI  - Treatment of esophageal submucosal tumors: endoscopic submucosal tunneling
      dissection versus thoracoscopic enucleation.

PMID- 29061263
TI  - Response.

PMID- 29061264
TI  - Retreatment after failure of per-oral endoscopic myotomy: Does "cutting" fare
      better than "stretching"?

PMID- 29061266
TI  - Erratum.

PMID- 29061265
TI  - Response.

PMID- 29061267
TI  - The DREAM remains the same.

PMID- 29061268
TI  - Look, listen, and feel.

PMID- 29061269
TI  - Comparison of percutaneous versus open femoral cutdown access for endovascular
      repair of ruptured abdominal aortic aneurysms.
AB  - OBJECTIVE: Ruptured endovascular aortic aneurysm repair (REVAR) is being
      increasingly used to treat ruptured abdominal aortic aneurysms (rAAAs). However,
      the comparison between totally percutaneous (pREVAR) vs femoral cutdown (cREVAR)
      access for REVAR has not been studied. We used a national surgical database to
      evaluate the 30-day outcomes in patients undergoing pREVAR vs cREVAR. METHODS:
      Patients who underwent EVAR for rAAA between 2011 and 2014, inclusively, were
      studied in the American College of Surgeons (ACS) National Surgical Quality
      Improvement Program (NSQIP) targeted vascular database. Univariate and
      multivariate analyses were used to compare preoperative demographics, operation
      specific variables, and postoperative outcomes between those who had pREVAR and
      cREVAR. RESULTS: We identified 502 patients who underwent REVAR, of which 129 had
      pREVAR (25.7%) and 373 cREVAR (74.3%). Between 2011 and 2014, the use of totally
      percutaneous access for repair increased from 14% to 32%. Of all patients
      undergoing REVAR, 24% had bilateral percutaneous access, 2% had attempted
      percutaneous access converted to cutdown, 64% had bilateral femoral cutdowns, and
      10% had single femoral cutdown. Univariate analysis showed there were no
      significant differences in age, gender, body mass index, AAA size, or other high
      risk physiologic comorbidities between the two groups. There was also no
      difference in rates of preoperative hemodynamic instability (48.1% vs 45.0%; P =
      .55) or need for perioperative transfusion (67.4% vs 67.8%; P = .94). There was a
      higher incidence of use of regional anesthesia for pREVAR compared with cREVAR
      (20.9% vs 7.8%; P < .01). The incidence of postoperative wound complications was
      similar between both groups (4.8% vs 5.4%; P = .79), whereas hospital length of
      stay was shorter in the pREVAR group (mean difference, 1.3 days). Overall 30-day
      mortality was higher in the pREVAR group (28.7% vs 20.1%; P = .04), and operative
      time was longer (mean difference, 6.3 minutes). However, when pREVARs done in
      2011 to 2012 were compared with those done in 2013 to 2014, 30-day mortality
      decreased from 38.2% to 25.3% and operative time decreased by 25 minutes (188 to
      163 minutes). Multivariate analysis showed there were no significant differences
      in mortality, wound complications, hospital length of stay, or operative time
      between pREVAR and cREVAR. CONCLUSIONS: The ACS NSQIP targeted vascular database
      shows that there has been increased adoption of pREVAR in recent years, with
      improved mortality and operative time over the 4-year study period. At this
      point, pREVAR has not yet been shown to be superior to cREVAR for rAAA, but these
      outcome improvements are encouraging and likely attributable to increased
      operator experience.

PMID- 29061271
TI  - Invited commentary.

PMID- 29061272
TI  - Invited commentary.

PMID- 29061273
TI  - Invited commentary.

PMID- 29061270
TI  - Long-term survival and secondary procedures after open or endovascular repair of
      abdominal aortic aneurysms.
AB  - OBJECTIVE: Randomized trials have shown an initial survival benefit of
      endovascular over conventional open abdominal aortic aneurysm repair but no long
      term difference up to 6 years after repair. Longer follow-up may be required to
      demonstrate the cumulative negative impact on survival of higher reintervention
      rates associated with endovascular repair. METHODS: We updated the results of the
      Dutch Randomized Endovascular Aneurysm Management (DREAM) trial, a multicenter,
      randomized controlled trial comparing open with endovascular aneurysm repair, up
      to 15 years of follow-up. Survival and reinterventions were analyzed on an
      intention-to-treat basis. Causes of death and secondary interventions were
      compared by use of an events per person-year analysis. RESULTS: There were 178
      patients randomized to open and 173 to endovascular repair. Twelve years after
      randomization, the cumulative overall survival rates were 42.2% for open and
      38.5% for endovascular repair, for a difference of 3.7 percentage points (95%
      confidence interval, -6.7 to 14.1; P = .48). The cumulative rates of freedom from
      reintervention were 78.9% for open repair and 62.2% for endovascular repair, for
      a difference of 16.7 percentage points (95% confidence interval, 5.8-27.6; P =
      .01). No differences were observed in causes of death. Cardiovascular and
      malignant disease account for the majority of deaths after prolonged follow-up.
      CONCLUSIONS: During 12 years of follow-up, there was no survival difference
      between patients who underwent open or endovascular abdominal aortic aneurysm
      repair, despite a continuously increasing number of reinterventions in the
      endovascular repair group. Endograft durability and the need for continued
      endograft surveillance remain key issues.

PMID- 29061274
TI  - Inflammatory aneurysm of ileocolic artery discovered on fluorine 18
      fluorodeoxyglucose-positron emission tomography/computed tomography.

PMID- 29061275
TI  - Proposed Quality Payment Program changes for 2018.

PMID- 29061276
TI  - Inpatient coding and the diagnosis-related group.

PMID- 29061277
TI  - Regarding "Current practice of thoracic outlet decompression surgery in the
      United States".

PMID- 29061279
TI  - Reply.

PMID- 29061278
TI  - Regarding "Reoperation rates after open and endovascular abdominal aortic
      aneurysm repairs".

PMID- 29061280
TI  - Oral dysesthesia: A perplexing problem for practitioners.

PMID- 29061281
TI  - Electroencephalographic and peripheral temperature dynamics during a prolonged
      psychomotor vigilance task.
AB  - Attention lapses and fatigue are a main source of impaired performance that can
      lead to accidents. This study analyzed electroencephalographic (EEG) dynamics and
      body skin temperature as markers of attentional fluctuations in non-sleep
      deprived subjects during a 45min Psychomotor Vigilance Task (PVT). Independent
      Component Analysis and time-frequency analysis were used to evaluate the EEG
      data. Results showed a positive association between distal and distal-to-proximal
      gradient (DPG) temperatures and reaction time (RT); increments in EEG power in
      alpha-, theta- and beta-band frequencies in parieto-occipital, central-medial and
      frontal components, were associated with poor performance (slower RT) in the
      task. This generalized power increment fits with an increased activity in the
      default mode network, associated with attention lapses. This study highlights the
      potential use of the PVT as a tool to obtain individual physiological indices of
      vigilance and fatigue that could be applied to other vigilance tasks typically
      performed in occupational settings.

PMID- 29061282
TI  - Analgesic efficacy of laparoscopic-guided transverse abdominis plane block using
      liposomal bupivacaine in bariatric surgery.
AB  - BACKGROUND: Postoperative pain management is a major contributor to recovery and
      discharge in bariatric surgery. Local anesthetic agents are of particular
      interest: they're non-sedating and may reduce postoperative pain and hospital
      length of stay (LOS). DESIGN: Researchers queried the Bariatric Surgery Service
      Database for patients undergoing laparoscopic weight loss surgery from January
      2012-December 2014. Patients were divided between those who did and did not
      receive liposomal bupivacaine intra-operatively. Measures included demographics,
      narcotic use, LOS, antiemetic use, and pain scales. RESULTS: The liposomal group
      consisted of 233 patients and the PCA group consisted of 243 patients. The
      liposomal group had significantly less narcotic use than the PCA group in terms
      of IV morphine equivalents. This did not translate into a reduction in LOS in the
      liposomal group. CONCLUSIONS: TAP block using liposomal bupivacaine provides
      effective analgesia comparable to PCA.

PMID- 29061283
TI  - Liver resection for metastases not of colorectal, neuroendocrine, sarcomatous, or
      ovarian (NCNSO) origin: A multicentric study.
AB  - BACKGROUND: Liver resection is a well-established treatment for colorectal,
      neuroendocrine and sarcomatous metastases but remains ill-defined for metastases
      from other primary sites. This study aimed to analyze the outcomes of hepatic
      resection for metastases not of colorectal, neuroendocrine, sarcomatous, or
      ovarian (NCNSO) origin and to identify predictors of outcome. METHODS:
      Retrospective analysis of patients undergoing resection for NCNSO metastases in
      three western centers. Patients were analyzed according to the primary cancer.
      Outcomes were recurrence and survival. RESULTS: We analyzed 188 patients, divided
      in: gastrointestinal (59), breast (59) and "others" (70). Median time to
      recurrence was 15.3 months, while median survival was 52 months. Survival at 1,
      3, and 5 years was 78%, 60.4% and 47.8%, respectively. In term of prognostic
      factors, metastases >35 mm from gastrointestinal tumors were associated with
      lower survival (p = 0.029) and age>60 years was associated with better survival
      in breast metastases (p = 0.018). CONCLUSIONS: Liver resection for NCNSO
      metastases is feasible and results in long-term survival are similar to
      colorectal metastases. In gastrointestinal metastases, size (<35 mm) could be
      used to select patients.

PMID- 29061284
TI  - Corrosion behavior of titanium in response to sulfides produced by Porphyromonas
      gingivalis.
AB  - OBJECTIVE: To investigate the effects of sulfides produced by Porphyromonas
      gingivalis (P. gingivalis) on the corrosion behavior of titanium. METHODS:
      Commercially pure titanium disks were mirror-polished and immersed in culture
      medium (BHI), spent medium after culturing P. gingivalis (BHI-S), and culture
      medium with P. gingivalis (BHI-P), and incubated aerobically at 37 degrees C for
      3-14 days. Titanium corrosion was evaluated through surface observation (using
      scanning electron microscope: SEM), color change (DeltaE*ab), glossiness (Gs(20
      degrees )), chemical composition and state (using X-ray photoelectron
      spectroscopy: XPS), and titanium release. RESULTS: DeltaE*ab and Gs(20 degrees )
      did not significantly differ among specimens placed in test mediums for the study
      duration (p>0.05). SEM images of specimens showed no signs of localized or
      overall corrosion. XPS analysis indicated showed clear titanium metal state peaks
      on all specimens in addition to sulfide and sulfate on BHI-S and BHI-P specimens.
      Valency fraction of titanium decomposed from Ti2p spectrum of BHI-S and BHI-P
      specimens indicated no progression of oxidation. No significant levels of
      titanium release were found regardless of the mediums' sulfide content. Results
      suggested that sulfides produced by P. gingivalis attached on the surface of
      titanium specimens but did not cause titanium corrosion over the immersion period
      of 14 days. SIGNIFICANCE: It is imperative for dental practitioners to be aware
      of any elements which may influence the clinical success of titanium implants.

PMID- 29061285
TI  - Cuspal flexure of composite-restored typodont teeth and correlation with
      polymerization shrinkage values.
AB  - OBJECTIVE: The relationship between post-gel shrinkage, total shrinkage, and
      cuspal flexure was examined. Cuspal flexure was measured on restored typodont
      teeth, which offered a standardized tooth shape for comparison of shrinkage
      stress effects among restorative composites. METHODS: Six restorative composites
      were compared (Filtek LS, Venus Flowable, Tetric EvoCeram, Filtek Flowable,
      Esthet-X, and Filtek Supreme). Total shrinkage was determined from changes in
      projected surface area before and after polymerization (n=10). Post-gel shrinkage
      was determined with a biaxial strain gauge that measured strain development
      during polymerization (n=10). Cuspal flexure was determined using typodont
      maxillary second premolars with standard MOD slot preparation (n=10). Flexure was
      determined by comparing the three-dimensionally scanned cuspal surfaces before
      and after restoration. Restoration bonding to the typodont cavity was achieved by
      sandblasting and adhesive application. Bond integrity was verified by measuring
      dye penetration. Results were analyzed using ANOVA and Student-Newman-Keuls post
      hoc test (significance level 0.05). Pearson was used for correlations. RESULTS:
      Total and post-gel shrinkage were significant different for all composites (t
      test; P<0.001). Depending on the composite, only 9-41% of the total shrinkage was
      recorded as post-gel shrinkage. Bond integrity of restored typodont teeth was 96
      99%. Cuspal flexure correlated strongly with post-gel shrinkage, but there was no
      correlation with total shrinkage. SIGNIFICANCE: Cuspal flexure of restored
      typodont teeth showed the effect of shrinkage stress caused by polymerizing
      composite restorations, ensuring standardization while maintaining the effects of
      tooth/cavity geometry. Post-gel shrinkage gave a good indication to screen
      composites for the stress they may generate; total shrinkage had no direct
      correlation with stress.

PMID- 29061287
TI  - CO2 Laser Treatment is Effective for Symptoms of Vaginal Atrophy.

PMID- 29061286
TI  - Eleostearic phospholipids as probes to evaluate antioxidants efficiency against
      liposomes oxidation.
AB  - Regardless of the applications: therapeutic vehicle or membrane model to mimic
      complex biological systems; it is of a great importance to develop simplified,
      reproducible and rapid model assays allowing for a relevant assessment of the
      liposomal membrane oxidation and therefore antioxidant activity of selected
      molecules. Here, we describe a new and high-throughput assay that we called
      "Vesicle Conjugated Autoxidizable Triene (VesiCAT)". It is based on specific UV
      absorbance spectral properties of a new phospholipid probe, synthesized with
      natural conjugated eleostearic acid extracted from Tung oil. The VesiCAT assay
      has been developed with two different radical generators (2,2'-azobis(2
      amidinopropane) dihydrochloride; AAPH and 2,2'-azobis(2,4-dimethylvaleronitrile);
      AMVN), producing a constant flux of oxidant species, either in membrane or in
      aqueous phase. This method appears very efficient in assessing the effect of
      various pure antioxidant molecules in their ability to preserve liposomes from
      oxidative degradation. In addition, the AAPH- and AMVN-induced oxidations offer
      the possibility of extracting different but complementary information with
      respect to the antioxidants efficacy.

PMID- 29061288
TI  - CO2 Laser Treatment is Effective for Symptoms of Vaginal Atrophy: No.

PMID- 29061289
TI  - Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment:
      Series report and literature review.
AB  - INTRODUCTION AND OBJECTIVES: Olfactory neuroblastoma (ONB) is a rare entity that
      constitutes less than 5% of nasosinusal malignancies. Mainstream treatment
      consists in surgical resection+/-adjuvant radiotherapy. By exposing results
      observed with apparition of new therapeutic options as neoadjuvant chemotherapy,
      the objective is to evaluate a series and a review of the current literature.
      METHODS: A retrospective review was conducted including patients diagnosed and
      followed-up for ONB from 2008 to 2015 in our institution. RESULTS: 9 patients
      were included. Mean follow-up of 52.5 months (range 10-107). Kadish stage: A, 1
      patient (11.1%) treated with endoscopic surgery; B, 2 patients (22.2%) treated
      with endoscopic surgery (one of them received adjuvant radiotherapy); C, 6
      patients (66.7%), 4 patients presented intracranial extension and were treated
      with neoadjuvant chemotherapy followed by surgery and radiotherapy. The other 2
      patients presented isolated orbital extension, treated with radical surgery
      (endoscopic or craniofacial resection) plus radiotherapy. The 5-year disease free
      and overall survival observed was 88.9%. CONCLUSION: Neoadjuvant chemotherapy
      could be an effective treatment for tumor reduction, improving surgical resection
      and reducing its complications.

PMID- 29061290
TI  - Beyond time and space: The effect of a lateralized sustained attention task and
      brain stimulation on spatial and selective attention.
AB  - The Theory of Visual Attention (TVA) provides a mathematical formalisation of the
      "biased competition" account of visual attention. Applying this model to
      individual performance in a free recall task allows the estimation of 5
      independent attentional parameters: visual short-term memory (VSTM) capacity,
      speed of information processing, perceptual threshold of visual detection;
      attentional weights representing spatial distribution of attention (spatial
      bias), and the top-down selectivity index. While the TVA focuses on selection in
      space, complementary accounts of attention describe how attention is maintained
      over time, and how temporal processes interact with selection. A growing body of
      evidence indicates that different facets of attention interact and share common
      neural substrates. The aim of the current study was to modulate a spatial
      attentional bias via transfer effects, based on a mechanistic understanding of
      the interplay between spatial, selective and temporal aspects of attention.
      Specifically, we examined here: (i) whether a single administration of a
      lateralized sustained attention task could prime spatial orienting and lead to
      transferable changes in attentional weights (assigned to the left vs right hemi
      field) and/or other attentional parameters assessed within the framework of TVA
      (Experiment 1); (ii) whether the effects of such spatial-priming on TVA
      parameters could be further enhanced by bi-parietal high frequency transcranial
      random noise stimulation (tRNS) (Experiment 2). Our results demonstrate that
      spatial attentional bias, as assessed within the TVA framework, was primed by
      sustaining attention towards the right hemi-field, but this spatial-priming
      effect did not occur when sustaining attention towards the left. Furthermore, we
      show that bi-parietal high-frequency tRNS combined with the rightward spatial
      priming resulted in an increased attentional selectivity. To conclude, we present
      a novel, theory-driven method for attentional modulation providing important
      insights into how the spatial and temporal processes in attention interact with
      attentional selection.

PMID- 29061291
TI  - Clinical Research in Dermatology and Venereology in Spanish Research Centers in
      2005 Through 2014: Results of the MaIND Study.
AB  - BACKGROUND AND OBJECTIVE: Bibliometric indicators provide a useful measure of the
      number of clinical research articles published in scientific journals and their
      quality. This study aimed to assess the amount and quality of research carried
      out in Spanish dermatology centers and to describe the research topics. MATERIAL
      AND METHOD: Bibliometric study of clinical research articles that met the
      inclusion criteria and had a definitive publication date between 2005 and 2014 in
      MEDLINE or Embase in which the corresponding author's affiliation was a Spanish
      hospital dermatology department or other center. RESULTS: Of 8,617 articles
      found, 1,104 (12.81%) met the inclusion criteria. The main reason for excluding
      articles was that they did not have an evidence level of 4 or better. The main
      vehicle for reporting was the journal Actas Dermosifiliograficas, which published
      326 articles (29.53%). Melanoma, the disease the researchers studied most often,
      accounted for 134 articles (12.13%). LIMITATIONS: A limitation to bear in mind
      when interpreting the results is that we relied on the corresponding author's
      affiliation to identify articles reflecting research from a Spanish dermatology
      center. Thus, studies in which dermatologists participated would not be
      recognized if they were directed by other specialists. CONCLUSION: Only a small
      portion of articles published from Spanish dermatology centers can be considered
      clinical research, mainly because many publications provide a low level of
      scientific evidence. Most publications are case reports.

PMID- 29061292
TI  - [Hyperprolactinemia with galactorrhea induced by lansoprazole: A case report].

PMID- 29061293
TI  - Methylphenidate: Gender trends in adult and pediatric populations over a 7year
      period.
AB  - OBJECTIVE: Methylphenidate (MPH) is a prescription-stimulant medication which is
      authorized in France for two indications: attention-deficit hyperactivity
      disorder in children (aged>=6years) and narcolepsy in cases where modafinil is
      ineffective (for children and adults). MPH use has increased worldwide in the
      past 2 decades in children and adults. Different pharmacoepidemiological
      Europeans studies have described MPH patterns of use. To our knowledge, few
      pharmacoepidemiological studies have described MPH patterns of use in France.
      METHODS: In this context, we have performed a study on regional reimbursement
      database (PACA-Corse area, covering approximately 4 millions inhabitants). The
      first part of the study analyzed the evolution of MPH users characteristic's
      yearly (grouped by age and gender) over a 7year period (2005-2011). In order to
      better characterize patterns of MPH use in adults, a specific analyze has been
      performed in the second part on MPH adult users in 2011 with a gender descriptive
      approach. RESULTS: During the 7year period, MPH dispensing grew from 0.28 to 0.68
      patient per 1000. The proportion of adult patients rose from 14.8 to 25.7%
      (P<0.0001), with patients mainly aged 35-49years old. Gender differences in MPH
      users were noted between adults and children: the proportion of girls was less
      important in children than in adult (in 2011, 20.7% of girls among children vs
      44.9% among adults). Moreover, the proportion of girls among children increased
      between 2005 to 2011 (15.1% of girls in 2005 versus 20.7% in 2011). Among adults,
      women were prescribed more antidepressants (41.5% versus 28.2%, P=0.003) and less
      opiate maintenance treatments (22.4% versus 31.9%, P=0.03) than men. Finally, 11%
      of men and 16.4% of women were over 50years old. CONCLUSION: MPH prescription
      greatly increased over7years, especially in adults. Moreover, in this population,
      patterns of MPH use differed with gender specificities. Such findings may
      increase clinical attention on monitoring MPH use in adults.

PMID- 29061294
TI  - Monitoring of aeolian desertification on the Qinghai-Tibet Plateau from the 1970s
      to 2015 using Landsat images.
AB  - Aeolian desertification, one of the most serious environmental issues, has
      hampered socioeconomic development on the Qinghai-Tibet Plateau (QTP). However,
      research on aeolian desertification in this region has been limited. To develop a
      set of science-based preventive measures to mitigate desertification in this
      region, it is first necessary to clarify the status, evolution, and driving
      factors of aeolian desertification. In this study, based on extensive field
      investigations and a current classification system for aeolian desertification,
      we established a new system for interpreting aeolian desertified land (ADL) on
      the plateau using Landsat images from 1977, 1990, 2000, 2010, and 2015 and
      obtained the distribution of ADL through visual interpretation of the images. The
      results showed that ADL covered 392,914km2 (15.1% of the study area) in 2015,
      including gravel ADL, sandy ADL, and aeolian monadnocks. Controlled by climate,
      landforms, the type of Quaternary deposit, and human activities, ADL is scattered
      throughout the plateau but is concentrated mostly in the western and northern
      parts. Aeolian desertification on the plateau expanded from 1977 to 2000 and then
      began to reverse. The evolution during the study period is the result of the
      combined effects of natural and human factors. Irrational human activities were
      the dominant factor responsible for the expansion of ADL prior to 2000, whereas
      the subsequent reversal was mainly caused by climate change combined with large
      ecological restoration projects.

PMID- 29061296
TI  - Department of Error.

PMID- 29061297
TI  - Department of Error.

PMID- 29061298
TI  - Continued conundrum of PET-CT and Hodgkin's lymphoma.

PMID- 29061295
TI  - PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18):
      final results of an open-label, international, randomised phase 3 trial by the
      German Hodgkin Study Group.
AB  - BACKGROUND: The intensive polychemotherapy regimen eBEACOPP (bleomycin,
      etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and
      prednisone in escalated doses) is very active in patients with advanced-stage
      Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual
      patients might be cured with less burdensome therapy. We investigated whether
      metabolic response determined by PET after two cycles of standard regimen
      eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for
      PET-2-positive patients and reducing it for PET-2-negative patients. METHODS: In
      this open-label, randomised, parallel-group phase 3 trial, we recruited patients
      aged 18-60 years with newly diagnosed, advanced-stage Hodgkin's lymphoma in 301
      hospitals and private practices in Germany, Switzerland, Austria, the
      Netherlands, and the Czech Republic. After central review of PET-2, patients were
      assigned (1:1) to one of two parallel treatment groups on the basis of their PET
      2 result. Patients with positive PET-2 were randomised to receive six additional
      cycles of either standard eBEACOPP (8 * eBEACOPP in total) or eBEACOPP with
      rituximab (8 * R-eBEACOPP). Those with negative PET-2 were randomised between
      standard treatment with six additional cycles of eBEACOPP (8 * eBEACOPP) or
      experimental treatment with two additional cycles (4 * eBEACOPP). A protocol
      amendment in June, 2011, introduced a reduction of standard therapy to 6 *
      eBEACOPP; after this point, patients with positive PET-2 were no longer
      randomised and were all assigned to receive 6 * eBEACOPP and patients with
      negative PET-2 were randomly assigned to 6 * eBEACOPP (standard) or 4 * eBEACOPP
      (experimental). Randomisation was done centrally using the minimisation method
      including a random component, stratified according to centre, age (<45 vs >=45
      years), stage (IIB, IIIA vs IIIB, IV), international prognostic score (0-2 vs 3
      7), and sex. eBEACOPP was given as previously described; rituximab was given
      intravenously at a dose of 375 mg/m2 (maximum total dose 700 mg). The primary
      objectives were to show superiority of the experimental treatment in the PET-2
      positive cohort, and to show non-inferiority of the experimental treatment in the
      PET-2-negative cohort in terms of the primary endpoint, progression-free
      survival. We defined non-inferiority as an absolute difference of 6% in the 5
      year progression-free survival estimates. Primary analyses in the PET-2-negative
      cohort were per protocol; all other analyses were by intention to treat. This
      trial was registered with ClinicalTrials.gov, number NCT00515554. FINDINGS:
      Between May 14, 2008, and July 18, 2014, we recruited 2101 patients, of whom 137
      were found ineligible before randomisation and a further 19 were found ineligible
      after randomisation. Among 434 randomised patients (217 per arm) with positive
      PET-2, 5-year progression-free survival was 89.7% (95% CI 85.4-94.0) with
      eBEACOPP and 88.1% (83.5-92.7) with R-eBEACOPP (log-rank p=0.46). Patients with
      negative PET-2 randomly assigned to either 8 * eBEACOPP or 6 * eBEACOPP (n=504)
      or 4 * eBEACOPP (n=501) had 5-year progression-free survival of 90.8% (95% CI
      87.9-93.7) and 92.2% (89.4-95.0), respectively (difference 1.4%, 95% CI -2.7 to
      5.4). 4 * eBEACOPP was associated with fewer severe infections (40 [8%] of 498 vs
      75 [15%] of 502) and organ toxicities (38 [8%] of 498 vs 91 [18%] of 502) than
      were 8 * eBEACOPP or 6 * eBEACOPP in PET-2-negative patients. Ten treatment
      related deaths occurred: four in the PET-2-positive cohort (one [<1%] in the 8 *
      eBEACOPP group, three [1%] in the 8 * R-eBEACOPP group) and six in the PET-2
      negative group (six [1%] in the 8 * eBEACOPP or 6 * eBEACOPP group).
      INTERPRETATION: The favourable outcome of patients treated with eBEACOPP could
      not be improved by adding rituximab after positive PET-2. PET-2 negativity allows
      reduction to only four cycles of eBEACOPP without loss of tumour control. PET-2
      guided eBEACOPP provides outstanding efficacy for all patients and increases
      overall survival by reducing treatment-related risks for patients with negative
      PET-2. We recommend this PET-2-guided treatment strategy for patients with
      advanced-stage Hodgkin's lymphoma. FUNDING: Deutsche Krebshilfe, Swiss State
      Secretariat for Education and Research, and Roche Pharma AG.

PMID- 29061299
TI  - Challenges and Recent Advances in Medulloblastoma Therapy.
AB  - Medulloblastoma (MB) is the most common childhood brain tumor, which occurs in
      the posterior fossa. MB tumors are highly heterogeneous and have diverse genetic
      make-ups, with differential microRNA (miRNA) expression profiles and variable
      prognoses. MB can be classified into four subgroups, each with different origins,
      pathogenesis, and potential therapeutic targets. miRNA and small-molecule
      targeted therapies have emerged as a potential new therapeutic paradigm in MB
      treatment. However, the development of chemoresistance due to surviving cancer
      stem cells and dysregulation of miRNAs remains a challenge. Combination therapies
      using multiple drugs and miRNAs could be effective approaches. In this review we
      discuss various MB subtypes, barriers, and novel therapeutic options which may be
      less toxic than current standard treatments.

PMID- 29061300
TI  - MtHsp70-CLIC1-pulsed dendritic cells enhance the immune response against ovarian
      cancer.
AB  - Approximately 80% of ovarian cancer (OC) is diagnosed at late stages, and most
      patients die within 5 years of diagnosis due to recurrence or drug resistance.
      Novel treatments are required to improve patient survival. Immune therapy against
      cancer is promising; however, therapeutic vaccination has been limited by the
      inability of tumor antigens to induce effective immune responses. Chloride
      intracellular channel 1 (CLIC1) was previously identified as a possible tumor
      marker for OC. In this study, we constructed a recombinant protein by conjugating
      the extracellular domain of CLIC1 to the carboxyl terminus of Mycobacterium
      tuberculosis heat shock protein 70 (MtHsp70). Human dendritic cells (DCs) derived
      from cortical blood were pulsed with the fusion protein, and the antitumor effect
      of human cytotoxic T lymphocytes (CTLs) stimulated by autologous DCs was assessed
      in NOG mice. MtHsp70-CLIC1 promoted the phenotypic maturation of human DCs and
      the secretion of Th1-associated cytokines in vitro. MtHsp70-CLIC1-stimulated CTLs
      generated a CLIC1-specific immune response both in vitro and in vivo. These
      results indicate that DCs pulsed with MtHsp70-CLIC1 can enhance antitumor
      immunity against OC, providing a novel immune therapeutic strategy.

PMID- 29061301
TI  - Stoichiometry and mechanistic implications of the MacAB-TolC tripartite efflux
      pump.
AB  - The MacAB-TolC tripartite efflux pump is involved in resistance to macrolide
      antibiotics and secretion of protein toxins in many Gram-negative bacteria. The
      pump spans the entire cell envelope and operates by expelling substances to
      extracellular space. X-ray crystal and electron microscopic structures have
      revealed the funnel-like MacA hexamer in the periplasmic space and the
      cylindrical TolC trimer. Nonetheless, the inner membrane transporter MacB still
      remains ambiguous in terms of its oligomeric state in the functional complex. In
      this study, we purified a stable binary complex using a fusion protein of MacA
      and MacB of Escherichia coli, and then supplemented MacA to meet the correct
      stoichiometry between the two proteins. The result demonstrated that MacB is a
      homodimer in the complex, which is consistent with results from the recent
      complex structure using cryo-electron microscopy single particle analysis.
      Structural comparison with the previously reported MacB periplasmic domain
      structure suggests a molecular mechanism for regulation of the activity of MacB
      via an interaction between the MacB periplasmic domain and MacA. Our results
      provide a better understanding of the tripartite pumps at the molecular level.

PMID- 29061302
TI  - Mitophagy regulates macrophage phenotype in diabetic nephropathy rats.
AB  - Imbalance of M1/M2 macrophages phenotype activation is a key point in diabetic
      nephropathy (DN). Macrophages mainly exhibit M1 phenotype, which contributes to
      the inflammation and fibrosis in DN. Studies indicate that autophage plays an
      important role in M1/M2 activation. However, the effect of mitophage on M1/M2
      macrophage phenotype transformation in DN is unknown. This study investigates the
      role of mitophage on macrophage polarization in DN. In vivo experiments show that
      macrophages are exhibited to M1 phenotype and display a lower level of mitophagy
      in the kidney of streptozocin (STZ)-induced diabetic rats. Additionally,
      inducible nitric oxide synthase (iNOS) expression is positive correlated with the
      P62 expression, while negative correlated with LC3. Electronic microscope
      analysis shows mitochondria swelling, crista decrease and lysosome reduction in
      DN rats compared with NC rats. In vitro, RAW264.7 macrophages switch to M1
      phenotype under high glucose conditions. Mitophagy is downregulated in such high
      glucose induced M1 macrophages. Furthermore, macrophages tend to switch to the M1
      phenotype, expressing higher iNOS and TNF-alpha when impair mitophagy by 3-MA.
      Rapamycin, an activator of mitophagy, signifcantly blocks high-glucose induced M1
      makers (iNOS and TNF-alpha) expression, meanwhile enhances M2 makers (MR and Arg
      1) expression. These results demonstrate that mitophage participates in the
      regulation of M1/M2 macrophage phenotype in diabetic nephropathy.

PMID- 29061303
TI  - Unique binding mode of Evogliptin with human dipeptidyl peptidase IV.
AB  - Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert
      butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of
      dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2
      diabetes in South Korea. In this study, we report the crystal structures of
      Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to
      human DPP4. Analysis of both the structures and inhibitory activities suggests
      that the binding of the trifluorophenyl moiety in the S1 pocket and the
      piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S2
      extensive subsite, and that the multiple hydrogen bonds made by the (R)-beta
      amine group in the S2 pocket and the contacts made by the (R)-tert-butyl group
      with Arg125 contribute to the high potency observed for Evogliptin.

PMID- 29061304
TI  - Crystal structure of the kinase and UBA domains of SNRK reveals a distinct UBA
      binding mode in the AMPK family.
AB  - Sucrose non-fermenting (Snf1)-related kinase (SNRK) is a novel member of the AMP
      activated protein kinase (AMPK) family and is involved in many metabolic
      processes. Here we report the crystal structure of an N-terminal SNRK fragment
      containing kinase and adjacent ubiquitin-associated (UBA) domains. This structure
      shows that the UBA domain binds between the N- and C-lobes of the kinase domain.
      The mode of UBA binding in SNRK largely resembles that in AMPK and brain specific
      kinase (BRSK), however, unique interactions play vital roles in stabilizing the
      KD-UBA interface of SNRK. We further propose a potential role of the UBA domain
      in the regulation of SNRK kinase activity. This study provides new insights into
      the structural diversities of the AMPK kinase family.

PMID- 29061305
TI  - Redox regulation of plant S-nitrosoglutathione reductase activity through post
      translational modifications of cysteine residues.
AB  - Nitric oxide (NO) is considered as a signalling molecule involved in a variety of
      important physiological and pathological processes in plant and animal systems.
      The major pathway of NO reactions in vivo represents S-nitrosation of thiols to
      form S-nitrosothiols. S-nitrosoglutathione reductase (GSNOR) is the key enzyme in
      the degradation pathway of S-nitrosoglutathione (GSNO), a low-molecular weight
      adduct of NO and glutathione. GSNOR indirectly regulates the level of protein S
      nitrosothiol in the cells. This study was focused on the dynamic regulation of
      the activity of plant GSNORs through reversible S-nitrosation and/or oxidative
      modifications of target cysteine residues. Pre-incubation with NO/NO- donors or
      hydrogen peroxide resulted in a decreased reductase and dehydrogenase activity of
      all studied plant GSNORs. Incubation with thiol reducing agent completely
      reversed inhibitory effects of nitrosative modifications and partially also
      oxidative inhibition. In biotin-labelled samples, S-nitrosation of plant GSNORs
      was confirmed after immunodetection and using mass spectrometry S-nitrosation of
      conserved Cys271 was identified in tomato GSNOR. Negative regulation of
      constitutive GSNOR activity in vivo by nitrosative or oxidative modifications
      might present an important mechanism to control GSNO levels, a critical mediator
      of the downstream signalling effects of NO, as well as for formaldehyde
      detoxification in dehydrogenase reaction mode.

PMID- 29061306
TI  - SUMOylation represses the transcriptional activity of the Unfolded Protein
      Response transducer ATF6.
AB  - The Unfolded Protein Response (UPR) is a cascade of intracellular stress
      signaling from the endoplasmic reticulum (ER) that protect the cells from the
      stress caused by accumulation of unfolded or misfolded proteins in the ER.
      Activating transcription factor 6 (ATF6) is one of primary UPR transducers that
      remodels the stressed cells through transcriptional regulation. Although the
      activation mechanism and biological roles of ATF6 have been well studied, the
      understanding of the negative or feedback regulation of ATF6 remains elusive. In
      this report, we showed that ATF6 protein can be modified by small ubiquitin-like
      modification (SUMOylation) and that the transcriptional activity of ATF6 is
      negatively regulated by SUMOylation. We identified that SUMOylation of ATF6 is
      significantly increased in the cells expressing misfolded cystic fibrosis
      transmembrane conductance regulator (CFTR) encoded by the mutant human CFTR gene
      (dF508CFTR). Further analyses revealed two highly conserved SUMOylation motifs
      within the trans-activation domain of ATF6 protein of human, mouse, or rat
      specie. The human ATF6 protein can be SUMOylated mediated through the small
      ubiquitin-like modifier protein 1 (SUMO-1) and E3 SUMO-protein ligase 1 (PIAS1)
      at the conserved sumoylation residue Lys149 that is located at the N-terminal of
      the activated form of ATF6 protein. Bimolecular fluorescence complementation
      (BiFC) analysis confirmed that the activated ATF6 protein can be SUMOylated and
      that the ATF6 sumoylation occurs in the nuclei. Moreover, trans-activation
      reporter analysis demonstrated that SUMOylation of the ATF6 protein at the
      conserved residue Lys149 represses the transcriptional activity of ATF6. In
      summary, our study revealed a negative regulation of the UPR transducer ATF6
      through post-translational SUMOylation. The information from this study will not
      only increase our understanding of the fine-tuning regulation of the UPR
      signaling but will also be informative to the modulation of the UPR for
      therapeutic benefits.

PMID- 29061307
TI  - PYK2 mediates BzATP-induced extracellular matrix proteins synthesis.
AB  - Mechanical stimuli such as fluid shear and cyclic tension force induced
      extracellular adenosine triphosphate (ATP) release in osteoblasts. In particular,
      cyclic tension force-induced ATP enhances bone formation through P2X7 activation.
      Proline-rich tyrosine kinase 2 (PYK2) mediate osteoblasts differentiation is
      induced by mechanical stimuli. Furthermore, activation of PYK2 also was a
      response to integrin by mechanical stimuli. Extracellular matrix protein (ECMP)s,
      which are important factors for bone formation are expressed by osteoblasts.
      However, the effect of the interaction of 2'(3)-Omicron-(4-Benzoylbenzoyl)
      adenosine-5'-triphosphate (BzATP), which is the agonist of the mechanosensitive
      receptor P2X7, with PYK2 on ECMP production is poorly understood. Thus, our
      purpose was to investigate the effects of PYK2 on BzATP-induced ECMP production
      in osteoblasts. BzATP increased phospho-PYK2 protein expression on days 3 and 7
      of culture. Furthermore, the PYK2 inhibitor PF431394 inhibited the stimulatory
      effect of BzATP on the expression of type I collagen, bone sialoprotein and
      osteocalcin expression. PF431396 did not inhibit the stimulatory effect of BzATP
      on osteopontin (OPN) mRNA expression. These results suggest that mechanical
      stimuli activate P2X7 might induce ECMPs expression through PYK2 except in the
      case of OPN expression. Altogether, mechanical stimuli-induced ECMPs production
      might be implicated by extracellular ATP secretion or integrin via PYK2
      activation.

PMID- 29061308
TI  - EBV-encoded EBNA1 regulates cell viability by modulating miR34a-NOX2-ROS
      signaling in gastric cancer cells.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is a viral protein expressed
      in all EBV-infected cells that induces malignant transformation. EBNA1 is
      reported to contribute to tumor progression through an increase in reactive
      oxygen species via nicotinamide adenine dinucleotide phosphate oxidase. However,
      the underlying molecular mechanism of EBNA1-induced ROS accumulation in gastric
      cancer is poorly understood. Here, we demonstrated that miR34a regulation by
      EBNA1 determined cell fate in EBV-infected gastric cancer cells. ROS content and
      NOX2 expression were higher in EBNA1-expressing SNU719 cells than in EBNA1
      nonexpressing SNU638 cells. Downregulation of NOX2 using siRNA technology in
      SNU719 cells decreased cell viability and ROS content. Regulation of EBNA1
      expression in EBV-associated gastric cancers modulated NOX2 expression, ROS
      content and cell viability. We also showed that upregulation of NOX2 by EBNA1 was
      mediated by downregulating miRNA34a. Finally, overexpression of miR34a in EBNA1
      expressing SNU719 cells induced typical apoptosis, suggesting that reactivation
      of miR34a in EBNA1-expressing gastric cancer cells could be a strategy for
      treatment of EBV-infected gastric cancer cells.

PMID- 29061309
TI  - Natural and artificial radionuclides in a marine core. First results of 236U in
      North Atlantic Ocean sediments.
AB  - There are very few data available of 236U in marine sediment cores. In this study
      we present the results from the first oceanic depth profile of 236U in a sediment
      core sampled in the North Atlantic Ocean, at the PAP site (4500 m depth,
      Porcupine Abyssal Plain (PAP) site, 49 degrees 0' N, 16 degrees 30' W).
      Additionally, the sediment core was radiologically characterized through the
      measurement of anthropogenic 137Cs, 239Pu, 240Pu, 129I and 14C and natural 210Pb,
      40K and 226Ra. The measured 236U concentrations decrease from about 90.106 at g-1
      at the seafloor down to 0.5.106 at g-1 at 6 cm depth. They are several orders of
      magnitude lower than the reported values for soils from the Northern Hemisphere
      solely influenced by global fallout (i.e. from 2700.106 to 7500.106 at g-1).
      236U/238U atom ratios measured are at least three orders of magnitude above the
      estimated level for the naturally occurring dissolved uranium. The obtained
      inventories are 1.1012 at m-2 for 236U, 80 Bq m-2 for 137Cs, 45 Bq m-2 for
      239+240Pu and 2.6.1012 at m-2 for 129I. Atomic ratios for 236U/239Pu, 137Cs/236U
      and 129I/236U, obtained from the inventories are 0.036, 0.11 and 2.5
      respectively. Concentration profiles show mobilization probably due to
      bioturbation from the abundant detritivore holothurian species living at the PAP
      site sea-floor. The range of 236U, 137Cs, 239+240Pu and 129I values, inventories
      and ratios of these anthropogenic radionuclides are more similar to the values
      due to fall-out than values from a contribution from the Nuclear Fuel
      Reprocessing Plants dispersed to the south-west of the North Atlantic Ocean.
      However, signs of an additional source are detected and might be associated to
      the nuclear wastes dumped on the Eastern North Atlantic Ocean.

PMID- 29061310
TI  - Dietary program and physical activity impact on biochemical markers in patients
      with type 2 diabetes: A systematic review.
AB  - OBJECTIVES: Evaluate the effectiveness of the implementation of independently or
      combined dietary and physical activity programs on the blood glucose values and
      lipid profile in patients with type 2 diabetes, including participants aged 60
      years and over. DESIGN: Systematic review. DATA SOURCE: PubMed/Medline database,
      with language restrictions. Papers published between 2010 and 2016 were included.
      STUDY SELECTION: A total of 30 randomised controlled trials were included that
      focused on physical activity and dietary interventions in patients with type 2
      diabetes mellitus and include participants aged 60 years and over. RESULTS: The
      selected articles have shown that the implementation of physical activity
      programs (aerobic, resistance, flexibility and combined exercises), and programs
      based on a higher intake of vegetables, grains, legumes, fruits, unsaturated
      fatty acids, as well as consumption of foods with low glycaemic index, calorie
      restriction, intake of probiotics, vitamin D supplementation and educational
      sessions about diabetes improves blood glucose levels, as well as the lipid
      profile, in patients with type 2 diabetes. CONCLUSIONS: Physical activity and
      dietary programs are fundamental in the treatment and metabolic control of type 2
      diabetes mellitus.

PMID- 29061311
TI  - Efficacy of high doses of penicillin versus amoxicillin in the treatment of
      uncomplicated community acquired pneumonia in adults. A non-inferiority
      controlled clinical trial.
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is treated with penicillin in
      some northern European countries. OBJECTIVES: To evaluate whether high-dose
      penicillin V is as effective as high-dose amoxicillin for the treatment of non
      severe CAP. DESIGN: Multicentre, parallel, double-blind, controlled, randomized
      clinical trial. SETTING: 31 primary care centers in Spain. PARTICIPANTS: Patients
      from 18 to 75 years of age with no significant associated comorbidity and with
      symptoms of lower respiratory tract infection and radiological confirmation of
      CAP were randomized to receive either penicillin V 1.6 million units, or
      amoxicillin 1000mg three times per day for 10 days. MAIN MEASUREMENTS: The main
      outcome was clinical cure at 14 days, and the primary hypothesis was that
      penicillin V would be non-inferior to amoxicillin with regard to this outcome,
      with a margin of 15% for the difference in proportions. EudraCT register 2012
      003511-63. RESULTS: A total of 43 subjects (amoxicillin: 28; penicillin: 15) were
      randomized. Clinical cure was observed in 10 (90.9%) patients assigned to
      penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of
      -9.1% (95% CI, -41.3% to 6.4%; p=.951) for non-inferiority. In the intention-to
      treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI,
      7.3-58.1%; p=.009 for superiority). The number of adverse events was similar in
      both groups. CONCLUSIONS: There was a trend favoring high-dose amoxicillin versus
      high-dose penicillin in adults with uncomplicated CAP. The main limitation of
      this trial was the low statistical power due to the low number of patients
      included.

PMID- 29061312
TI  - An additional measurement of glycated albumin can help prevent missed diagnosis
      of diabetes in Chinese population.
AB  - BACKGROUND: In subjects who present a first fasting plasma glucose (FPG1)
      >=7.0mmol/l without classic symptoms of diabetes, diagnosis of diabetes will
      likely be missed without an additional oral glucose tolerance test (OGTT) in the
      Chinese population. Recent studies have shown that glycated albumin (GA) has
      advantages in reflecting postprandial hyperglycemia. Therefore, the present study
      evaluated whether additional measurement of GA could reduce the rate of missed
      diagnosis of diabetes. METHODS: A total of 1287 participants (711 men, 576 women)
      with a FPG1>=7.0mmol/l without classic symptoms of diabetes were enrolled and
      underwent a 75-g OGTT. Serum GA was measured by a liquid enzyme method. Diabetes
      was diagnosed based on the 2010 American Diabetes Association (ADA) criteria.
      RESULTS: A total of 992 (77.08%) participants were diagnosed diabetes by OGTT and
      glycated hemoglobin A1c (HbA1c). The diagnostic validity of 2-h postload plasma
      glucose (2hPG) was superior to other glycemic index (the diagnostic sensitivity
      of 2hPG, HbA1c, the second FPG (FPG2) was 87.50%, 73.99%, 63.21%, respectively).
      Without 2hPG after OGTT, repeat testing of FPG2 alone would result in missed
      diagnosis of 36.79% of diabetic participants, whereas testing FPG2 with HbA1c was
      associated with a missed diagnosis rate of 14.31%. While using the combined
      criteria of FPG2>=7.0mmol/l and/or HbA1c>=6.5% and/or GA>=17.1%, the rate of
      missed diagnosis was merely 9.48%. That is, the rate of missed diagnosis was
      reduced by 33.75% with the addition of GA measurement. The k value reflecting the
      consistency of diagnosis between the FPG2 and/or HbA1c and/or GA criteria and the
      2010 ADA criteria was 0.788. CONCLUSIONS: For subjects with FPG1 >=7.0mmol/l
      without classic symptoms of diabetes, additional measurement of GA can help
      prevent missed diagnosis of diabetes in Chinese population.

PMID- 29061313
TI  - Day-night temperature differential, rather than mean temperature, determines age
      of sexual maturation in Straicosta albicosta (Noctuidae).
AB  - While pheromone traps have been effectively used to monitor the recent range
      expansion of the western bean cutworm (WBC), very little is known about the
      pheromone mediated reproductive biology of this species. The age at which females
      initiated calling (the behaviour associated with the release of the sex
      pheromone), and the pattern of calling on the first three nights following sexual
      maturation were determined for virgin females held under four temperature regimes
      (25:20; 25:15; 20:15; 20:10  degrees C L:D and 16L:8D photoperiod), and two RH
      (60 and 80%). Regardless of the rearing conditions the pre-calling period (PCP)
      was always several days post emergence, supporting the hypothesis that WCB is a
      migrant species. However, surprisingly the length of the PCP was not directly
      related to mean temperature but rather to the temperature differential between
      the photophase and the scotophase. The duration of calling increased with female
      age, but unlike in other moths was not affected by the abiotic factors tested.
      The relative insensitivity to temperature and humidity, when compared with many
      other moth species, may be related to the WBC being a univoltine species with a
      mid-summer flight period. Consequently, there would not be strong selection
      pressure for plasticity in calling behavior when compared with the case of
      multivoltine species that experience a wide range of environmental conditions
      during different seasonal flight periods.

PMID- 29061314
TI  - Tumor-infiltrating lymphocytes in Breast Cancer and implications for clinical
      practice.
AB  - Breast Cancer (BC) can be classified using pathologic features, such as grade and
      tumor size. It can be categorized based on the gene expression profile, which
      identifies the distinct molecular subtype. More recently, stromal tissue has been
      recognized as an important modulator of tumor cell growth, pathogenesis, and
      progression. Immune cells could drive important clinical characteristics that
      affect BC outcomes. Subgroups of patients who have tumor-infiltrating lymphocytes
      in the stroma may have better response to chemotherapy and favorable long-term
      prognosis. Accumulating evidence shows that the immune system plays a crucial
      role in the outcomes of some BC subgroups, especially more aggressive,
      proliferative ones such as triple-negative and HER2-positive BC. This review
      article will present data on the role of lymphocyte infiltration in BC prognosis
      and response to therapy. This review will also introduce the reader to the
      challenges of applying this promising prognostic and predictive biomarker in
      clinical practice.

PMID- 29061315
TI  - Metallothionein prevents doxorubicin cardiac toxicity by indirectly regulating
      the uncoupling proteins 2.
AB  - Doxorubicin (Dox) is a broad-spectrum anticancer agent, but its clinical use is
      restricted due to irreversible cardiac toxicity. Metallothionein (MT) can inhibit
      Dox-induced cardiac toxicity. Applying a proteomics approach we determined that
      uncoupling proteins (UCPs) may be implicated in this process. This study was
      designed to examine the mechanisms of MT against Dox cardiac toxicity and the
      link between MT and UCP2. In vivo, wild-type (MT+/+) and MT-I/II null (MT-/-)
      mice were given a single dose of Dox (15 mg/kg, i.p.) and sacrificed at 4 days
      after Dox injection. In vitro, cardiomyocytes were prepared from MT-/- and MT+/+
      neonatal mice and cardiomyocytes were pretreated with typical antioxidant NAC or
      the UCP2 inhibitor genipin followed by exposure to Dox. Based on the results,
      genipin enhanced Dox-induced oxidative injury, particularly in MT-/-
      cardiomyocyte. UCP2 levels in MT-/- mice were significantly lower compared to
      MT+/+ mice treated with Dox. Co-immunoprecipitation demonstrated that MT did not
      directly bind to UCP2. The NAC and Nrf2 activator oltipraz inhibit the decrease
      of UCP2 expression induced by Dox. Therefore, attenuating free radical damage
      with UCP2 help MT antagonize the Dox-induced cardiac toxicity, but does not
      directly bind MT. MT may regulate UCP2 expression by up-regulating Nrf2.

PMID- 29061316
TI  - Tea polyphenols ameliorates neural redox imbalance and mitochondrial dysfunction
      via mechanisms linking the key circadian regular Bmal1.
AB  - Circadian rhythms are autonomous anticipatory oscillators that control a large
      array of physiological and metabolic processes. Compelling evidence points toward
      an interplay between circadian rhythms and cellular redox metabolism.
      Dysregulation of circadian rhythms is associated with neurodegenerative diseases
      and accelerated aging. Tea polyphenols (TP) is one of the most used antioxidants
      and exerts beneficial effect on neurodegenerative diseases. The aim of this study
      is to investigate whether circadian clock mechanisms are involved in the
      protection effect of TP against neural redox imbalance and mitochondrial
      dysfunction in SH-SY5Y cells. In the current study, our results revealed that TP,
      as a Bmal1-enhancing natural compound, can reverse the relatively shallow daily
      oscillations of circadian clock genes transcription and protein expression in SH
      SY5Y neuronal cells under oxidative stress conditions. Furthermore, TP
      pretreatment significantly ameliorated H2O2-elicited mitochondria impairment via
      manipulating mitochondrial dynamics and mitochondrial membrane potential, which
      is consistent with the recovery in expression of mitochondrial respiration
      complex I-IV in Bmal1-dependent efficiency. Furthermore, Bmal1 is involved in TP
      stimulated Nrf2/ARE/HO-1 and AKT/CREB/BDNF signaling pathway. Hence, TP may serve
      as a nutritional preventive strategy in the recovery of oxidative stress-related
      neurodegenerative disease via modulating circadian clock.

PMID- 29061317
TI  - Exposure assessment for dioxin-like PCBs intake from organic and conventional
      meat integrating cooking and digestion effects.
AB  - In this paper, exposure to Polychlorinated biphenyls (PCBs) related to bovine
      meat consumption is assessed based on multiples sources of data, namely data
      collected within the national research project "SoMeat" that objectively assesses
      the potential risks and benefits of organic and conventional food production
      systems in terms of contaminants respective contents. The work focuses on dioxin
      like PCBs in bovine meat in France. A modular Bayesian approach is proposed
      including measures after production, effect of cooking, levels and frequency of
      consumption and effect of digestion. In each module, a model is built and prior
      information can be integrated through previously acquired data commonly used in
      food risk assessment or vague priors. The output of the global model is the
      exposure including both production modes (organic and conventional) for three
      different cooking intensities (rare, medium, and well-done), before digestion and
      after digestion. The main results show that organic meat is more contaminated
      than conventional meat in mean after production stage and after cooking although
      cooking reduces the contamination level. This work is a first step of refined
      risk assessment integrating different steps such as cooking and digestion in the
      context of chemical risk assessment similarly to current microbiological risk
      assessments.

PMID- 29061318
TI  - The neuropeptides and protein hormones of the agricultural pest fruit fly
      Bactrocera dorsalis: What do we learn from the genome sequencing and tissue
      specific transcriptomes?
AB  - Neuropeptides and protein hormones are very important signaling molecules, and
      are involved in the regulation and coordination of various physiological
      processes in invertebrates and vertebrates. Using a bioinformatics approach, we
      screened the recently sequenced genome and six tissue-specific transcriptome
      databases (central nervous system, fat body, ovary, testes, male accessory
      glands, antennae) of the oriental fruit fly (Bactrocera dorsalis) that is
      economically one of the most important pest insects of tropical and subtropical
      fruit. Thirty-nine candidate genes were found to encode neuropeptides or protein
      hormones. These include most of the known insect neuropeptides and protein
      hormones, with the exception of adipokinetic hormone-corazonin-related peptide,
      allatropin, diuretic hormone 34, diuretic hormone 45, IMFamide, inotocin, and sex
      peptide. Our results showed the neuropeptides and protein hormones of Diptera
      insects appear to have a reduced repertoire compared to some other insects.
      Moreover, there are also differences between B. dorsalis and the super-model of
      Drosophila melanogaster. Interesting features of the oriental fruit fly are the
      absence of genes coding for sex peptide and the presence of neuroparsin and two
      genes coding neuropeptide F. The majority of the identified neuropeptides and
      protein hormones is present in the central nervous system, with only a limited
      number of these in the other tissues. Moreover, we predicted their physiological
      functions via comparing with data of FlyBase and FlyAtlas. Taken together, owing
      to the large number of identified peptides, this study can be used as a reference
      about structure, tissue distribution and physiological functions for comparative
      studies in other model and important pest insects.

PMID- 29061320
TI  - Arginine vasopressin signaling in the suprachiasmatic nucleus on the resilience
      of circadian clock to jet lag.
AB  - Almost all organisms on Earth have an internal biological clock, known as the
      circadian clock. This clock system drives robust oscillations in metabolism,
      physiology, and behavior, such as hormone secretions, blood pressure, and
      sleep/wake cycles, with a period of approximately 24h. In mammals, circadian
      rhythms are generated by a timing system comprised of a master pacemaker located
      in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, which
      orchestrates the clocks in the peripheral tissues. Jet lag, caused by an abrupt
      change of environmental light-dark cycles, induces a temporal misalignment of the
      output signal from SCN. We revealed that arginine vasopressin/V1 receptor
      signaling in the SCN plays a critical role in the resilience of the circadian
      clock to jet lag. I here discuss a model of SCN neuronal system under a jet lag
      condition.

PMID- 29061319
TI  - Discriminating between mothers' infant- and adult-directed speech: Cross
      linguistic generalizability from Japanese to Italian and German.
AB  - The aim of the present work was a cross-linguistic generalization of Inoue et
      al.'s (2011) algorithm for discriminating infant- (IDS) vs. adult-directed speech
      (ADS). IDS is the way in which mothers communicate with infants; it is a
      universal communicative property, with some cross-linguistic differences. Inoue
      et al. (2011) implemented a machine algorithm that, by using a mel-frequency
      cepstral coefficient and a hidden Markov model, discriminated IDS from ADS in
      Japanese. We applied the original algorithm to two other languages that are very
      different from Japanese - Italian and German - and then tested the algorithm on
      Italian and German databases of IDS and ADS. Our results showed that: First, in
      accord with the extant literature, IDS is realized in a similar way across
      languages; second, the algorithm performed well in both languages and close to
      that reported for Japanese. The implications for the algorithm are discussed.

PMID- 29061321
TI  - Robotic Parastomal Hernia Repair With Biologic Mesh.
AB  - INTRODUCTION: Parastomal hernia is a common and vexing problem after ileal
      conduit urinary diversion that can cause pain, bowel symptoms, and problems with
      the stoma appliance, resulting in leakage, odor, and impairment of quality of
      life. Historically, these hernias have been managed open surgically, which
      requires considerable dissection of the abdominal wall for mesh placement, and
      may also require relocating the stoma to the contralateral side. Further, open
      parastomal hernia repair can be a morbid procedure with recurrence rates of
      approximately 30%. MATERIALS AND METHODS: We present our technique of robotic
      parastomal hernia repair with a biologic mesh. We used a biologic mesh with the
      keyhole technique to avoid risk of erosion into the bowel segment. We present a
      case series of 3 patients undergoing robotic parastomal hernia repair. The
      illustrative case in the video is that of a 63-year-old obese woman with a
      parastomal hernia resulting in poor stoma appliance adhesion and bothersome
      urinary leakage. RESULTS: Robotic repair was completed successfully without
      intraoperative complications in all 3 patients. The mean age was 72 years. Mean
      body mass index was 30 kg/m2. Mean operating time was 3.5 hours. Mean estimated
      blood loss was 7.5 mL. Mean length of hospital stay was 3 days. On follow-up, all
      3 patients were asymptomatic with stoma appliance issues and had no recurrence.
      CONCLUSION: Our initial series suggests that robotic repair of parastomal hernia
      is safe and feasible with minimal morbidity and good short-term outcomes. Further
      studies are required to confirm the efficacy of our technique.

PMID- 29061322
TI  - Exposure to neonicotinoid insecticides induces embryotoxicity in mice and
      rabbits.
AB  - The potential toxicity of neonicotinoids (thiacloprid, acetamiprid, thiamethoxam
      and clothianidin) as well as related commercial products Calypso 480SC
      (thiacloprid mixture), Mospilan 20SP (acetamiprid mixture) and Agita 10WG
      (thiamethoxam mixture) on developmental capacities and quality of preimplantation
      embryos was evaluated. During in vitro tests, isolated 2-cell stage mice embryos
      were cultured in media with various concentrations of active compounds or
      commercial products until blastocyst formation. As found using stereomicroscopic
      examination, all neonicotinoids at highest (100MUM) concentration negatively
      affected embryonic development (P<0.001). Fluorescence staining revealed that the
      blastocysts obtained displayed lower numbers of blastomeres and elevated
      incidence of cell death. Thiacloprid and acetamiprid decreased quality of
      blastocysts also at 10MUM concentration. From the tested products only Calypso
      480SC containing 10MUM of thiacloprid showed harmful impact on embryo quality. In
      an experiment using rabbit embryos, similar negative effect of thiacloprid in
      vitro was recorded. In vivo testing confirmed that blastocysts collected from
      thiacloprid-treated mice displayed lower total cell counts than blastocysts from
      controls. The sensitivity of embryonic cells to neonicotinoids is in the order of
      thiacloprid>acetamiprid, thiomethoxam>clothianidin. Thiacloprid impairs
      development and quality of both mouse and rabbit preimplantation embryos, and
      shows embryotoxicity even at acute reference dose.

PMID- 29061323
TI  - Comparison of continuous glucose monitoring in adolescents with type 1 diabetes:
      Ramadan versus non-Ramadan.
AB  - AIM: To assess the impact of fasting on interstitial glucose (IG) in adolescents
      with type 1 DM (T1DM) by using continuous glucose monitoring (CGM). METHOD: A
      minimum of 2.5 days CGM was done on adolescents with T1DM during fasting in
      Ramadan and in the month before or after Ramadan to compare the differences in
      mean IG, and in the durations of hypoglycemia (<70 mg/dL), hyperglycemia (200-299
      mg/dL), and severe hyperglycemia (>=300 mg/dL). RESULTS: Fourteen adolescents
      were studied, age 15 +/- 4 years, duration of diabetes 6 +/- 4 years, and HbA1C
      8.6 +/- 1.1% (70.3 mmol/mol). There was no difference in the mean IG (190 +/- 39
      and 180 +/- 37, p= 0.4), or in the durations of hypoglycemia (5.14 +/- 5% and
      7.03 +/- 4.9%, p=0.3), hyperglycemia (25.35 +/- 11.3% and 24.24 +/- 10.1%
      (P=0.7)), and severe hyperglycemia (13.21 +/- 13.4% and 10.96 +/- 10.6%, P=0.6),
      between Ramadan and, non-Ramadan, respectively. CONCLUSION: Adolescents with T1DM
      have the same wide fluctuation in IG during fasting in Ramadan as they do outside
      Ramadan. Insulin regimen adjustment should be targeting both extremes of glucose
      abnormality.

PMID- 29061324
TI  - Acyclovir chemical kinetics with the discovery and identification of newly
      reported degradants and degradation pathways involving formaldehyde as a
      degradant and reactant intermediate.
AB  - The purpose of this research was to determine acyclovir (ACV) acidic degradation
      kinetics which is relevant to gastric retentive device product design. A
      stability-indicating method revealed two unknown degradation products which have
      been identified by mass spectrometry as ACV and guanine formaldehyde adducts. In
      addition to the formation of these adducts, a proposed degradation scheme
      identifies the formation of methyl acetal ethylene glycol, formaldehyde, ethylene
      glycol, and guanine as additional ACV degradation products. pH-rate profiles were
      explained by using a rate law which assumed acid-catalyzed hydrolysis of
      protonated and unprotonated ACV. The predicted and observed rate constants were
      in good agreement. Data-driven excipient selection recommendations were based on
      the chemical kinetic study results, degradation scheme, and pH-rate profiles. The
      average activation energy for the degradation reaction was determined to be
      31.3+/-1.6kcal/mol. The predicted ACV t90% at 37 degrees C and pH 1.2 was
      calculated to be 7.2days. As a first approximation, this suggests that ACV
      gastric retentive devices designed to deliver drug for 7days should have
      acceptable drug product stability in the stomach.

PMID- 29061325
TI  - Simplified stratum corneum model membranes for studying the effects of permeation
      enhancers.
AB  - The activity of transdermal permeation enhancers is usually evaluated in vitro on
      human or animal skin, but skin samples can be hard to source and highly variable.
      To provide a more consistent basis for evaluating the activity of permeation
      enhancers, we prepared relatively simple and inexpensive artificial membranes
      that imitate the stratum corneum (SC) lipid matrix. Our membranes were composed
      of stearic acid, cholesterol, cholesterol sulfate and a ceramide (CER) component
      consisting of N-2-hydroxystearoyl phytosphingosine (CER[AP]) and/or N-stearoyl
      phytosphingosine (CER[NP]). First, the permeation of theophylline (TH) and
      indomethacin (IND) through these membranes was compared with their permeation
      through porcine skin. Because the mixed CER[AP]/[NP] membrane gave the closest
      results to skin, this membrane was then used to test the effects of two
      permeation enhancers: N-dodecyl azepan-2-one (Azone) and (S)-N-acetylproline
      dodecyl ester (L-Pro2). Both enhancers significantly increased the flux of TH and
      IND through the skin and, even more markedly, through the lipid membrane, L-Pro2
      having a stronger effect than Azone. Thus, our simplified model of the SC lipid
      membrane based on phytosphingosine CERs appears to be suitable for mimicking skin
      permeation.

PMID- 29061326
TI  - Walk-in Model for Ill Care in an Urban Academic Pediatric Clinic.
AB  - OBJECTIVES: Since the Institute of Medicine's 2001 charge to reform health care,
      there has been a focus on the role of the medical home. Access to care in the
      proper setting and at the proper time is central to health care reform. We aimed
      to increase the volume of patients receiving care for acute illnesses within the
      medical home rather than the emergency department or urgent care center from 41%
      to 60%. METHODS: We used quality improvement methods to create a separate
      nonemergency care stream in a large academic primary care clinic serving 19,000
      patients (90% Medicaid). The pediatric primary care (PPC) walk-in clinic opened
      in July 2013 with service 4 hours per day and expanded to an all-day clinic in
      October 2013. Statistical process control methods were used to measure the change
      over time in the volume of ill patients and visits seen in the PPC walk-in
      clinic. RESULTS: Average weekly walk-in nonemergent ill-care visits increased
      from 61 to 158 after opening the PPC walk-in clinic. The percentage of
      nonemergent ill-care visits in the medical home increased from 41% to 45%. Visits
      during regular clinic hours increased from 55% to 60%. Clinic cycle time remained
      unchanged. CONCLUSIONS: Implementation of a walk-in care stream for acute illness
      within the medical home has allowed us to provide ill care to a higher proportion
      of patients, although we have not yet achieved our predicted volume. Matching
      access to demand is key to successfully meeting patient needs.

PMID- 29061327
TI  - Receipt of Medication and Behavioral Therapy Among a National Sample of School
      Age Children Diagnosed With Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVE: In 2011, the American Academy of Pediatrics published practice
      guidelines for attention-deficit/hyperactivity disorder (ADHD), recommending both
      medication and behavioral therapy for school-age children. The current study
      examines associations between child/family characteristics and ADHD medication,
      behavioral, and combined therapy. METHODS: This study used data from the 2014
      National Survey of the Diagnosis and Treatment of ADHD and Tourette syndrome, a
      nationally representative follow-up survey to the 2011-2012 National Survey of
      Children's Health. Descriptive statistics were used to estimate frequencies of
      ADHD treatments and multivariable logistic regression to examine child/family
      characteristics associated with parent-reported medication use, classroom
      management, and parent training for children aged 8 to 17 diagnosed with ADHD (n
      = 2401). RESULTS: Black and Hispanic children were less likely than white
      children to have ever received ADHD medication. Hispanic children were less
      likely than white children to be currently receiving medications (adjusted odds
      ratio, 0.49; 95% confidence interval, 0.30-0.80). No differences were found in
      current medication use for black children compared to white children. Thirty
      percent of parents reported that their child was currently receiving classroom
      management, and 31% reported having ever received parent training for ADHD.
      Children whose ADHD medication was managed by a primary care physician were less
      likely to receive combined medication and behavioral therapy compared to children
      managed by specialty physicians (adjusted odds ratio, 2.58; 95% confidence
      interval, 1.75-3.79). CONCLUSIONS: Most school-age children reported receiving
      medication for ADHD; however, medication disparities persist. Parent-reported use
      of behavioral therapies are low. Future research should examine reasons for
      observed variation in treatment and interventions to optimize ADHD care.

PMID- 29061328
TI  - Artificial Metalloenzymes on the Verge of New-to-Nature Metabolism.
AB  - Residing at the interface of chemistry and biotechnology, artificial
      metalloenzymes (ArMs) offer an attractive technology to combine the versatile
      reaction repertoire of transition metal catalysts with the exquisite catalytic
      features of enzymes. While earlier efforts in this field predominantly comprised
      studies in well-defined test-tube environments, a trend towards exploiting ArMs
      in more complex environments has recently emerged. Integration of these
      artificial biocatalysts in enzymatic cascades and using them in whole-cell
      biotransformations and in vivo opens up entirely novel prospects for both
      preparative chemistry and synthetic biology. We highlight selected recent
      developments with a particular focus on challenges and opportunities in the in
      vivo application of ArMs.

PMID- 29061329
TI  - Quantifying variant differences in DNA melting curves: Effects of length, melting
      rate, and curve overlay.
AB  - High resolution DNA melting of PCR products is a simple technique for sequence
      variant detection and analysis. However, sensitivity and specificity vary and
      depend on many factors that continue to be defined. We introduce the area between
      normalized melting curves as a metric to quantify genotype discrimination. The
      effects of amplicon size (51-547 bp), melting rate (0.01-0.64  degrees C/s) and
      analysis method (curve shape by overlay vs absolute temperature differences) were
      qualitatively and quantitatively analyzed. To limit experimental variance, we
      studied a single nucleotide variant with identical predicted wild type and
      homozygous variant stabilities by nearest neighbor thermodynamic theory.
      Heterozygotes were easier to detect in smaller amplicons, at faster melting
      rates, and after curve overlay (superimposition), with some p-values <10-20. As
      heterozygote melting rates increase, the relative magnitude of heteroduplex
      contributions to melting curves increases, apparently the result of non
      equilibrium processes. In contrast to heterozygotes, the interplay between curve
      overlay, PCR product size, and analysis method is complicated for homozygote
      genotype discrimination and is difficult to predict. Similar to temperature
      cycling in PCR, if the temperature control and temperature homogeneity of the
      solution are adequate, faster rates improve melting analysis, just like faster
      rates improve PCR.

PMID- 29061331
TI  - Screening for intracranial aneurysms in autosomal dominant polycystic kidney
      disease is cost-effective.
AB  - Intracranial aneurysm rupture is a dramatic complication of autosomal dominant
      polycystic kidney disease (ADPKD). It remains uncertain whether screening should
      be widespread or only target patients with risk factors (personal or familial
      history of intracranial aneurysm), with an at-risk profession, or those who
      request screening. We evaluated this in a single-center cohort of 495 consecutive
      patients with ADPKD submitted to targeted intracranial aneurysm screening.
      Cerebral magnetic resonance angiography was proposed to 110 patients with a
      familial history of intracranial aneurysm (group 1), whereas it was not our
      intention to propose it to 385 patients without familial risk (group 2). Magnetic
      resonance angiography results, intracranial aneurysm prophylactic repair, rupture
      events, and cost-effectiveness of intracranial aneurysm screening strategies were
      retrospectively analyzed. During a median follow up of 5.9 years, five non-fatal
      intracranial aneurysm ruptures occurred (incidence rate 2.0 (0.87-4.6)/1000
      patients-year). In group 1, 90% of patients were screened and an intracranial
      aneurysm was detected in 14, treated preventively in five, and ruptured in one
      patient despite surveillance. In group 2, 21% of patients were screened and an
      intracranial aneurysm was detected in five, and treated preventively in one.
      Intracranial aneurysm rupture occurred in four patients in group 2. Systematic
      screening was deemed cost-effective and provides a gain of 0.68 quality-adjusted
      life years compared to targeted screening. Thus, the intracranial aneurysm
      rupture rate is high in ADPKD despite targeted screening, and involves mostly
      patients without familial risk factors. Hence, cost-utility analysis suggests
      that intracranial aneurysm screening could be proposed to all ADPKD patients.

PMID- 29061330
TI  - A French point of view about the cost effectiveness of RASQ61R
      immunohistochemistry in colorectal cancer.

PMID- 29061332
TI  - Human plasmacytoid dendritic cells acquire phagocytic capacity by TLR9 ligation
      in the presence of soluble factors produced by renal epithelial cells.
AB  - Plasmacytoid dendritic cells (pDCs) are antigen presenting cells specialized in
      viral recognition through Toll-like receptor (TLR)7 and TLR9, and produce vast
      amounts of interferon alpha upon ligation of these TLRs. We had previously
      demonstrated a strong influx of pDCs in the tubulointerstitium of renal biopsies
      at the time of acute rejection. However, the role of human pDCs in mediating
      acute or chronic allograft rejection remains elusive. pDCs are thought to have a
      limited capacity to ingest apoptotic cells, critical for inducing CD4+ T cell
      activation via indirect antigen presentation and subsequent activation of
      antibody producing B cells. Here we tested whether the function of pDCs is
      affected by their presence within the graft. Maturation and interferon alpha
      production by pDCs was enhanced when cells were activated in the presence of
      viable HK2 renal epithelial cells. Importantly, soluble factors produced by
      cytomegalovirus-infected (primary) epithelial or endothelial cells enhanced pDC
      activation and induced their capacity to phagocytose apoptotic cells.
      Phagocytosis was not induced by free virus or soluble factors from non-infected
      cells. Activated pDCs showed an enhanced CD4+ and CD8+ T cell allostimulatory
      capacity as well as a potent indirect alloantigen presentation. Granulocyte
      Macrophage-Colony Stimulating Factor is one of the soluble factors produced by
      renal epithelial cells that, combined with TLR9 ligation, induced this functional
      capacity. Thus, pDCs present in the rejecting allograft can contribute to
      alloimmunity and potentially act as important orchestrators in the manifestation
      of acute and chronic rejection.

PMID- 29061333
TI  - Novel aspects of epitope matching and practical application in kidney
      transplantation.
AB  - This review describes the recent developments in the applicability and clinical
      significance of epitope matching in kidney transplantation. As incremental human
      leukocyte antigen (HLA) mismatches are associated with increased risk of
      rejection and allograft loss, HLA-matching remains one of the standard
      immunological triage tests to determine transplant suitability. Advancements in
      tissue-typing techniques have led to innovative concepts of HLA-matching at the
      epitope level. Epitopes are configurations of polymorphic amino acid residues
      that are recognized by B cells, and antibodies reactive with these epitopes lead
      to rejection and/or premature allograft loss. Even though there is substantial
      advancement in the characterization and understanding of epitopes, evidence
      supporting the added clinical benefit of epitope matching over traditional
      antigen matching and the ability to identify clinically relevant immunogenic
      epitopes remains poorly defined. We present an overview of the evidence
      surrounding the immunogenicity of mismatched donor epitopes and the applicability
      of HLA epitope matching in kidney transplantation. A better understanding of the
      immunogenicity and structural characteristics of HLA epitopes will guide
      clinicians to integrate epitope matching as an important parameter for donor
      selection in kidney transplantation.

PMID- 29061335
TI  - Research investments for UK infectious disease research 1997-2013: A systematic
      analysis of awards to UK institutions alongside national burden of disease.
AB  - INTRODUCTION: Infectious disease remains a significant burden in the UK and the
      focus of significant amounts of research investment each year. The Research
      Investments in Global Health study has systematically assessed levels of funding
      for infection research, and here considers investment alongside UK burden of
      individual infectious diseases. METHODS: The study included awards to UK
      institutions between 1997 and 2013 that were related to infectious disease.
      Awards related to global health projects were excluded here. UK burden data
      (mortality, years lived with disability, and disability adjusted life years) was
      sourced from the Global Burden of Disease study (IHME, USA). Awards were
      categorised by pathogen, disease, disease area and by type of science along the
      research pipeline (pre-clinical, phase I-III trials, product development, public
      health, cross-disciplinary research). New metrics present relative levels of
      funding by comparing sum investment with measures of disease burden. RESULTS:
      There were 5685 relevant awards comprising investment of L2.4 billion. By
      disease, HIV received most funding (L369.7m; 15.6% of the total investment). Pre
      clinical science was the predominant type of science (L1.6 billion, 68.7%), with
      the UK Medical Research Council (MRC) the largest funder (L714.8 million, 30.1%).
      There is a broad temporal trend to increased fundingper annum. Antimicrobial
      resistance received (L102.8 million, 4.2%), whilst sepsis received L23.6 million
      (1.0%). Compared alongside disease burden, acute hepatitis C and measles
      typically were relatively well-funded, whilst pneumonia, syphilis and gonorrhoea
      were poorly-funded. CONCLUSIONS: The UK has a broad research portfolio across a
      wide range of infectious diseases and disciplines. There are notable strengths
      including HIV, some respiratory infections and in pre-clinical science, though
      there was less funding for UK-relevant trials and public health research.
      Compared to the UK burden of disease, syphilis, gonorrhoea and pneumonia appear
      relatively neglected. Investment analyses can assist support policymakers to
      increase the equity of the UK R&D landscape.

PMID- 29061334
TI  - Neutrophil peptidyl arginine deiminase-4 has a pivotal role in
      ischemia/reperfusion-induced acute kidney injury.
AB  - Ischemia/reperfusion is a common cause of acute kidney injury (AKI). However,
      mechanisms underlying the sudden loss in kidney function and tissue injury remain
      to be fully elucidated. Here, we investigated the role of peptidyl arginine
      deiminase-4 (PAD4), which converts arginine to citrulline and plays a role in
      epigenetic regulation and inflammation, in renal ischemia/reperfusion injury.
      PAD4 expression was highly induced in infiltrating leukocytes 24 hours following
      renal ischemia and reperfusion. This induction was accompanied by citrullination
      of histone H3 and formation of neutrophil extracellular traps in kidneys of wild
      type mice. By contrast, PAD4-deficient mice did not form neutrophil extracellular
      traps, expressed lower levels of pro-inflammatory cytokines and were partially
      protected from renal ischemia/reperfusion-induced AKI. Furthermore, PAD4
      deficient mice recovered kidney function 48 hours after ischemia/reperfusion,
      whereas kidney function in the wild-type mice progressively worsened.
      Administration of DNase I, which degrades neutrophil extracellular traps or the
      PAD-specific inhibitor YW3-56 before ischemia, partially prevented renal
      ischemia/reperfusion-induced AKI. Notably, transfer of neutrophils from wild
      type, but not from PAD4-deficient mice, was sufficient to restore renal
      neutrophil extracellular trap formation and impair kidney function following
      renal ischemia/reperfusion. Thus, neutrophil PAD4 plays a pivotal role in renal
      ischemia/reperfusion-induced AKI.

PMID- 29061337
TI  - C reactive protein as a predictor of anastomotic leakage in colorectal surgery.
      Comparison between open and laparoscopic surgery.
AB  - INTRODUCTION: Anastomotic leak (AL) is a serious complication in colorectal
      surgery due to its increase in morbidity and mortality. The aim of this
      prospective non-randomised study is to determine whether C-reactive Protein (CRP)
      is useful as a predictor of AL in patients undergoing open versus laparoscopic
      surgery. METHODS: A total of 168 patients undergoing elective colorectal surgery
      were included. CRP was measured daily during the first 5postoperative days.
      Complications, specially AL, were analysed. RESULTS: Following an open approach
      32 patients (45.7%) presented complications, 15 (18.7%) in the laparoscopic group
      and 12 (29.4%) in the converted group (P=0.153). Following open surgery 9
      patients experienced AL, 5 were detected in the laparoscopic group and none in
      those converted (P=0.153). There were significant differences in CRP values
      between the 3 groups (P=0.03). ROC Curves showed AUC for the open and
      laparoscopic approach of 0.731 and 0.760 respectively. On day 4 the AUC was 0.867
      for the open group and 0.914 for the laparoscopic group. Cut-off points on day 4
      were: Open: 159.2mg/L; sensitivity 75%, specificity 89% and NPP 96% (P<0.001).
      Following laparoscopic surgery the cut-off point was 67.3%; sensitivity 100%,
      specificity 89.5% and NPP 100% (P=0.016). CONCLUSION: CRP on day 4 is useful to
      diagnose AL. Different cut-off values should be taken into account depending on
      the approach used.

PMID- 29061338
TI  - CTRP3 protected against doxorubicin-induced cardiac dysfunction, inflammation and
      cell death via activation of Sirt1.
AB  - BACKGROUND: Inflammation and myocytes apoptosis play critical roles in the
      development of doxorubicin (DOX)-induced cardiotoxicity. Our previous study found
      that C1q/tumour necrosis factor-related protein-3 (CTRP3) could inhibit cardiac
      inflammation and apoptosis of myocytes but its role in DOX-induced heart injury
      remains largely unknown. Our study aimed to investigate whether CTRP3 protected
      against DOX-induced heart injury and the underlying mechanism. METHODS: We
      overexpressed CTRP3 in the hearts using an adeno-associated virus system. The
      mice were subjected to a single intraperitoneal injection of DOX (15mg/kg) to
      induce short-term model for cardiomyopathy. The morphological examination and
      biochemical analysis were used to evaluate the effects of CTRP3. H9C2 cells were
      used to verify the protective role of CTRP3 in vitro. RESULTS: Myocardial CTRP3
      protein levels were reduced in DOX-treated mice. Cardiac specific-overexpression
      of CTRP3 preserved heart dysfunction, and attenuated cardiac inflammation and
      cell loss induced by DOX in vivo and in vitro. CTRP3 could activate silent
      information regulator 1 (Sirt1) in vivo and in vitro. Moreover, specific
      inhibitor of Sirt1 and the silence of Sirt1 could abolish the protective effects
      of CTRP3 against DOX-induced inflammation and apoptosis. CONCLUSION: CTRP3
      protected against DOX-induced heart injury via activation of Sirt1. CTRP3 has
      therapeutic potential for the treatment of DOX cardiotoxicity.

PMID- 29061339
TI  - HIC2 regulates isoform switching during maturation of the cardiovascular system.
AB  - Physiological changes during embryonic development are associated with changes in
      the isoform expression of both myocyte sarcomeric proteins and of erythrocyte
      haemoglobins. Cell type-specific isoform expression of these genes also occurs.
      Although these changes appear to be coordinated, it is unclear how changes in
      these disparate cell types may be linked. The transcription factor Hic2 is
      required for normal cardiac development and the mutant is embryonic lethal. Hic2
      embryos exhibit precocious expression of the definitive-lineage haemoglobin Hbb
      bt in circulating primitive erythrocytes and of foetal isoforms of cardiomyocyte
      genes (creatine kinase, Ckm, and eukaryotic elongation factor Eef1a2) as well as
      ectopic cardiac expression of fast-twitch skeletal muscle troponin isoforms. We
      propose that HIC2 regulates a switching event within both the contractile
      machinery of cardiomyocytes and the oxygen carrying systems during the
      developmental period where demands on cardiac loading change rapidly.

PMID- 29061340
TI  - Lawsone derivatives target the Wnt/beta-catenin signaling pathway in multidrug
      resistant acute lymphoblastic leukemia cells.
AB  - Multidrug resistance (MDR) represents a serious problem in cancer treatment. One
      strategy to overcome this obstacle is to identify agents that are selectively
      lethal to MDR cells. The aim of this study was to discover novel compounds
      against MDR leukemia and to determine the molecular mechanisms behind collateral
      sensitivity. A library of 1162 compounds was tested against parental, drug
      sensitive CCRF-CEM cells using the resazurin assay. A total of 302 compounds
      showed reasonable activity (less than 50% cell viability). Eleven out of 30
      lawsone derivatives revealed considerable collateral sensitivity in MDR P
      glycoprotein (Pgp)-overexpressing CEM/ADR5000 cells. They reduced beta-catenin
      activity in a Wnt/beta-catenin reporter cell line. Their activities significantly
      correlated with apolar desolvation (R = 0.819). Compound (1) (3-hydroxy-1,4-dioxo
      N-phenyl-naphthalene-2-carboxamide) was the most active compound and dose
      dependently down-regulated protein expression of beta-catenin, c-MYC, Pgp and
      Frizzled 7. By molecular docking, we predicted that compound (1) bound to the
      palmitoyl-binding groove of the cysteine-rich domain of Frizzled-7 and Frizzled
      8. Compound (1) neither stimulated ATPase activity of Pgp nor reactive oxygen
      species generation, both of which have been previously described as possible
      mechanisms of collateral sensitivity. Instead, we found that Wnt/beta-catenin
      signaling was selectively inhibited in CEM/ADR5000 cells, but not in CCRF-CEM
      cells. In conclusion, we found for the first time that the inhibition of Wnt/beta
      catenin signaling may represent a novel molecular mechanism of collateral
      sensitivity in MDR cells. Wnt/beta-catenin signaling, therefore, represents a
      potential therapeutic target for the selective killing of Pgp-mediated MDR.

PMID- 29061336
TI  - Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from
      the TB:HIV study.
AB  - OBJECTIVES: Mortality among HIV patients with tuberculosis (TB) remains high in
      Eastern Europe (EE), but details of TB and HIV management remain scarce. METHODS:
      In this prospective study, we describe the TB treatment regimens of patients with
      multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). RESULTS: A
      total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug
      resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was
      provided for 8% of patients with MDR-TB compared with 80% of those with pan
      susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5-74.1) of MDR-TB
      patients had started adequate treatment. While 67% received ART, HIV-RNA
      suppression was demonstrated in only 23%. CONCLUSIONS: Our results show that
      internationally recommended MDR-TB treatment regimens were infrequently used and
      that ART use and viral suppression was well below the target of 90%, reflecting
      the challenging patient population and the environment in which health care is
      provided. Urgent improvement of management of patients with TB/HIV in EE, in
      particular for those with MDR-TB, is needed and includes widespread access to
      rapid TB diagnostics, better access to and use of second-line TB drugs, timely
      ART initiation with viral load monitoring, and integration of TB/HIV care.

PMID- 29061341
TI  - Drug resistance induces the upregulation of H2S-producing enzymes in HCT116 colon
      cancer cells.
AB  - Hydrogen sulfide (H2S) production in colon cancer cells supports cellular
      bioenergetics and proliferation. The aim of the present study was to investigate
      the alterations in H2S homeostasis during the development of resistance to 5
      fluorouracil (5-FU), a commonly used chemotherapeutic agent. A 5-FU-resistant
      HCT116 human colon cancer cell line was established by serial passage in the
      presence of increasing 5-FU concentrations. The 5-FU-resistant cells also
      demonstrated a partial resistance to an unrelated chemotherapeutic agent,
      oxaliplatin. Compared to parental cells, the 5-FU-resistant cells rely more on
      oxidative phosphorylation than glycolysis for bioenergetic function. There was a
      significant increase in the expression of the drug-metabolizing cytochrome P450
      enzymes CYP1A2 and CYP2A6 in 5-FU-resistant cells. The CYP450 inhibitor
      phenylpyrrole enhanced 5-FU-induced cytotoxicity in 5-FU-resistant cells. Two
      major H2S-generating enzymes, cystathionine-beta-synthase (CBS) and 3
      mercaptopyruvate sulfurtransferase (3-MST) were upregulated in the 5-FU-resistant
      cells. 5-FU-resistant cells exhibited decreased sensitivity to the CBS inhibitor
      aminooxyacetate (AOAA) in terms of suppression of cell viability, inhibition of
      cell proliferation and inhibition of oxidative phosphorylation. However, 5FU
      resistant cells remained sensitive to the antiproliferative effect of benserazide
      (a recently identified, potentially repurposable CBS inhibitor). Taken together,
      the current data suggest that 5-FU resistance in HCT116 cells is associated with
      the upregulation of drug-metabolizing enzymes and an enhancement of endogenous
      H2S production. The anticancer effect of prototypical H2S biosynthesis inhibitor
      AOAA is impaired in 5-FU-resistant cells, but benserazide remains efficacious.
      Pharmacological approaches aimed at restoring the sensitivity of 5-FU-resistant
      cells to chemotherapeutic agents may be useful in the formulation of novel
      therapeutic strategies against colorectal cancer.

PMID- 29061343
TI  - EEG-Annotate: Automated identification and labeling of events in continuous
      signals with applications to EEG.
AB  - BACKGROUND: In controlled laboratory EEG experiments, researchers carefully mark
      events and analyze subject responses time-locked to these events. Unfortunately,
      such markers may not be available or may come with poor timing resolution for
      experiments conducted in less-controlled naturalistic environments. NEW METHOD:
      We present an integrated event-identification method for identifying particular
      responses that occur in unlabeled continuously recorded EEG signals based on
      information from recordings of other subjects potentially performing related
      tasks. We introduce the idea of timing slack and timing-tolerant performance
      measures to deal with jitter inherent in such non-time-locked systems. We have
      developed an implementation available as an open-source MATLAB toolbox
      (http://github.com/VisLab/EEG-Annotate) and have made test data available in a
      separate data note. RESULTS: We applied the method to identify visual
      presentation events (both target and non-target) in data from an unlabeled
      subject using labeled data from other subjects with good sensitivity and
      specificity. The method also identified actual visual presentation events in the
      data that were not previously marked in the experiment. COMPARISON WITH EXISTING
      METHODS: Although the method uses traditional classifiers for initial stages, the
      problem of identifying events based on the presence of stereotypical EEG
      responses is the converse of the traditional stimulus-response paradigm and has
      not been addressed in its current form. CONCLUSIONS: In addition to identifying
      potential events in unlabeled or incompletely labeled EEG, these methods also
      allow researchers to investigate whether particular stereotypical neural
      responses are present in other circumstances. Timing-tolerance has the added
      benefit of accommodating inter- and intra- subject timing variations.

PMID- 29061344
TI  - A matched-filter algorithm to detect amperometric spikes resulting from quantal
      secretion.
AB  - BACKGROUND: Electrochemical microelectrodes located immediately adjacent to the
      cell surface can detect spikes of amperometric current during exocytosis as the
      transmitter released from a single vesicle is oxidized on the electrode surface.
      Automated techniques to detect spikes are needed in order to quantify the spike
      rate as a measure of the rate of exocytosis. NEW METHOD: We have developed a
      Matched Filter (MF) detection algorithm that scans the data set with a library of
      prototype spike templates while performing a least-squares fit to determine the
      amplitude and standard error. The ratio of the fit amplitude to the standard
      error constitutes a criterion score that is assigned for each time point and for
      each template. A spike is detected when the criterion score exceeds a threshold
      and the highest-scoring template and the time of peak score is identified. The
      search for the next spike commences only after the score falls below a second,
      lower threshold to reduce false positives. The approach was extended to detect
      spikes with double-exponential decays with the sum of two templates. RESULTS:
      Receiver Operating Characteristic plots (ROCs) demonstrate that the algorithm
      detects >95% of manually identified spikes with a false-positive rate of ~2%.
      COMPARISON WITH EXISTING METHODS: ROCs demonstrate that the MF algorithm performs
      better than algorithms that detect spikes based on a derivative-threshold
      approach. CONCLUSIONS: The MF approach performs well and leads into approaches to
      identify spike parameters.

PMID- 29061345
TI  - BranchAnalysis2D/3D automates morphometry analyses of branching structures.
AB  - BACKGROUND: Morphometric analyses of biological features have become increasingly
      common in recent years with such analyses being subject to a large degree of
      observer bias, variability, and time consumption. While commercial software
      packages exist to perform these analyses, they are expensive, require extensive
      user training, and are usually dependent on the observer tracing the morphology.
      NEW METHOD: To address these issues, we have developed a broadly applicable, no
      cost ImageJ plugin we call 'BranchAnalysis2D/3D', to perform morphometric
      analyses of structures with branching morphologies, such as neuronal dendritic
      spines, vascular morphology, and primary cilia. RESULTS: Our BranchAnalysis2D/3D
      algorithm allows for rapid quantification of the length and thickness of
      branching morphologies, independent of user tracing, in both 2D and 3D data sets.
      COMPARISON WITH EXISTING METHODS: We validated the performance of
      BranchAnalysis2D/3D against pre-existing software packages using trained human
      observers and images from brain and retina. We found that the BranchAnalysis2D/3D
      algorithm outputs results similar to available software (i.e., Metamorph,
      AngioTool, Neurolucida), while allowing faster analysis times and unbiased
      quantification. CONCLUSIONS: BranchAnalysis2D/3D allows inexperienced observers
      to output results like a trained observer but more efficiently, thereby
      increasing the consistency, speed, and reliability of morphometric analyses.

PMID- 29061342
TI  - Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits
      and pitfalls.
AB  - Exercise exerts significant effects on the prevention and treatment of many
      diseases. However, even though some of the key regulators of training adaptation
      in skeletal muscle have been identified, this biological program is still poorly
      understood. Accordingly, exercise-based pharmacological interventions for many
      muscle wasting diseases and also for pathologies that are triggered by a
      sedentary lifestyle remain scarce. The most efficacious compounds that induce
      muscle hypertrophy or endurance are hampered by severe side effects and are
      classified as doping. In contrast, dietary supplements with a higher safety
      margin exert milder outcomes. In recent years, the design of pharmacological
      agents that activate the training program, so-called "exercise mimetics", has
      been proposed, although the feasibility of such an approach is highly debated. In
      this review, the most recent insights into key regulatory factors and therapeutic
      approaches aimed at leveraging exercise adaptations are discussed.

PMID- 29061346
TI  - Genotype-functional-phenotype correlations in photoreceptor guanylate cyclase (GC
      E) encoded by GUCY2D.
AB  - The GUCY2D gene encodes for the photoreceptor guanylate cyclase GC-E that
      synthesizes the intracellular messenger of photoreceptor excitation cGMP and is
      regulated by intracellular Ca2+-sensor proteins named guanylate cyclase
      activating proteins (GCAPs). Over 140 disease-causing mutations have been
      described so far in GUCY2D, 88% of which cause autosomal recessive Leber
      congenital amaurosis (LCA) while heterozygous missense mutations cause autosomal
      dominant cone-rod degeneration (adCRD). Mutations in GUCY2D are one of the major
      causes of all LCA cases and are the major cause of adCRD. A single amino acid,
      arginine at position 838, is likely to be the most sensitive one in GC-E as four
      single mutations and two complex mutations were reported to affect R838. The
      biochemical effect of 45 GC-E variants was studied showing a clear genotype
      phenotype correlation: LCA-causing mutations either show reduced ability or
      complete inability to synthesize cGMP from GTP, while CRD-causing mutations are
      functional, but shift the Ca2+-sensitivity of the GC-E - GCAP complex. Eight
      animal models of retinal guanylate cyclase deficiency have been reported
      including knockout (KO) mouse and chicken models. These two models were used for
      gene augmentation therapy that yielded promising results. Here we integrate the
      available information on the genetics, biochemistry and phenotype that is related
      to GUCY2D mutations. These data clearly show that mutation type (missense versus
      null) and localization (dimerization domain versus other protein domains) are
      correlated with the pattern of inheritance, impact on enzymatic function and
      retinal phenotype. Such clear correlation is unique to GUCY2D while mutations in
      many other retinal disease genes show variable phenotypes and lack of available
      biochemical assays.

PMID- 29061347
TI  - Reactogenicity and safety assessment of an attenuated nanovaccine against
      scorpion envenomation: Preclinical study.
AB  - An attenuated nanovaccine (Nps - V*) has been developed to protect humans from
      fatal scorpion envenomation in at-risk regions. This study was conducted to
      evaluate the toxicity and the local reactogenicity of the Nps - V* nanovaccine
      developed against Androctonus australis hector (Aah) venom. Assessment of the
      systemic inflammatory response and serum cytokine levels were evaluated in
      vaccinated mice with 100MUg of irradiated Aah venom (V*) encapsulated or not into
      polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c)
      route. The local reactogenicity was evaluated by dermal Draize observations and
      skin tissue analysis at the injection site of vaccinated rabbits with 250 or
      500MUg of V*-loaded into Nps. All animals gained weight and had normal food
      consumption during the study. Additionally, results showed that the
      nanoformulation Nps - V* did not cause clinical evidence of systemic toxicity in
      mice or rabbits, a transient edema/erythema at the injection site was only
      recorded as treatment-related reactogenicity. These results indicated a favorable
      safety profile for Nps - V* and supported its use in superior animal tests, then
      in a Phase 1 clinical trial.

PMID- 29061348
TI  - European Court of Justice ruling on vaccine liability and its implications for
      the United States.

PMID- 29061349
TI  - Patterns of childhood immunization and all-cause mortality.
AB  - BACKGROUND: Evidence supports the safety of the recommended childhood
      immunization schedule as a whole. However, additional research is warranted as
      parents' refusing or delaying vaccinations has increased in recent years. All
      cause mortality has been identified as a priority outcome to study in the context
      of the recommended immunization schedule. METHODS: We included children born
      January 1, 2004 through December 31, 2009, enrolled in the Vaccine Safety
      Datalink (VSD) from birth through 18 months of age. We examined vaccination
      patterns during the first 18 months of life among 8 vaccines, and identified
      deaths occurring between 19 and 48 months of age. We excluded children with
      complex chronic conditions, contraindications to vaccination, and deaths due to
      injuries, congenital anomalies, or diseases with onset prior to 19 months of age.
      We calculated mortality rates among children with different patterns of
      immunization, and incidence rate ratios (IRR) using the Cox proportional hazards
      model for children vaccinated according to the schedule versus undervaccinated
      children, adjusting for outpatient healthcare utilization, influenza vaccination,
      sex, and VSD site. RESULTS: Among 312,388 children in the study, 199,661 (64%)
      were vaccinated according to the schedule, and 112,727 (36%) were delayed or not
      vaccinated for at least one vaccine dose. Of 18 deaths eligible for analysis, 11
      occurred in children following the schedule (2.28 per 100,000 person-years), and
      seven occurred in undervaccinated children (2.57 per 100,000 person-years).
      Mortality rates among children following the schedule were not significantly
      different from those of undervaccinated children when excluding deaths with
      unknown causes (IRR = 1.29, 95% CI = 0.33-4.99), as well as when including deaths
      with unknown causes (IRR = 0.84, 95% CI = 0.32-2.99). CONCLUSION: Although there
      were few deaths, our results do not indicate a difference in risk of all-cause
      mortality among fully vaccinated versus undervaccinated children. Our findings
      support the safety of the currently recommended immunization schedule with regard
      to all-cause mortality.

PMID- 29061351
TI  - Survival of Endodontically Treated Roots/Teeth Based on Periapical Health and
      Retention: A 10-year Retrospective Cohort Study.
AB  - INTRODUCTION: The purpose of this retrospective longitudinal cohort study was to
      evaluate the outcome of nonsurgical root canal treatment (NSRCT), expressed as
      survival for both periapical health and retention of roots/teeth, as determined
      by clinical evaluation, periapical film/digital radiography (PFR/DPR), and cone
      beam computed tomography (CBCT) over 10 years, to determine the prognostic
      factors that influenced successful treatment outcomes. METHODS: A total of 132
      teeth (208 roots) with vital pulp received NSRCT at a university clinic. Eighteen
      factors (preoperative, intraoperative, and postoperative) were documented from
      the dental records and radiographs. Periapical indices with scores >=2 (PFR/DPR)
      and >=1 (CBCT) indicated the presence of a periapical lesion. Data were analyzed
      using the Kaplan-Meier test and the Cox proportional hazards regression model (P
      < .05). RESULTS: The estimated 10-year overall survival rates for periapical
      health of roots/teeth were 89.4%/88.6% with PFR, 89.4%/89.3% with DPR, and
      72.6%/69.7% with CBCT; the survival rate for root/tooth retention was
      90.4%/91.6%. CONCLUSIONS: The long-term outcome of NSRCT expressed as survival
      for periapical health was different with each radiographic method. Approximately
      more than 90% of the roots/teeth were retained for up to 10 years. The prognostic
      factors for periapical health were the disinfection of gutta-percha, missed
      canals, age, treatment sessions, and density of root filling (voids); the age and
      presence of a post were for root/tooth retention.

PMID- 29061350
TI  - Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50
      strain.
AB  - Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa
      and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans.
      Effective vaccination of susceptible ruminants is important for the prevention of
      RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in
      ruminants, whereas residual virulence might be a concern for vulnerable
      populations. It is also important for live-attenuated strains to encode unique
      genetic markers for the differentiation from wild-type RVFV strains. In this
      study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain
      via the introduction of 584 silent mutations. To minimize the impact on
      protective efficacy, codon usage and codon pair bias were not de-optimized. The
      resulting rMP12-GM50 strain showed 100% protective efficacy with a single
      intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization
      test. Moreover, outbred mice infected with one of three pathogenic reassortant
      ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%,
      or 30% survival, respectively. These results indicate that attenuation of the
      rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments.
      Recombinant RVFV vaccine strains encoding similar silent mutations will be also
      useful for the surveillance of reassortant strains derived from vaccine strains
      in endemic countries.

PMID- 29061352
TI  - A Cone-beam Computed Tomographic Study of Root and Canal Morphology of Maxillary
      First and Second Permanent Molars in a Thai Population.
AB  - INTRODUCTION: Understanding tooth anatomy is crucial for effective endodontic
      treatment. This study investigated the roots and root canal morphology of
      maxillary first and second permanent molars in a Thai population using cone-beam
      computed tomographic (CBCT) imaging. METHODS: This study evaluated 476 maxillary
      first molars and 457 maxillary second molars receiving CBCT examination and
      determined the number of roots and canal morphology according to Vertucci's
      classification, and the prevalence of a second mesiobuccal (MB2) canal in the
      mesiobuccal (MB) root was correlated with sex, age, and tooth side. RESULTS:
      Three roots were most commonly found in maxillary first and second molars. MB2
      canals in the MB root were found in 63.6% and 29.4% of first and second molars,
      respectively. The most common canal morphology in the first molar MB roots was
      type I (36.4%) followed by type II (28.8%), and type IV (25.3%). The most common
      canal morphology in the second molar MB roots was type I (70.6%) followed by type
      II (14.6%) and type IV (7.5%). Bilateral MB2 canals in the MB roots were present
      in 80.93% and 82.59% of the first and second molars, respectively. There was a
      significant correlation between males and the prevalence of MB2 canals in first
      molars (P < .05). CONCLUSIONS: CBCT imaging is useful to determine root canal
      morphology. The prevalence of MB2 canals is approximately 60% and 30% in first
      and second molars, respectively. Furthermore, bilateral MB2 canals were commonly
      found. Our results can help endodontists to improve endodontic treatment
      outcomes.

PMID- 29061353
TI  - Intraradicular Appearances Affect Radiographic Interpretation of the Periapical
      Area.
AB  - INTRODUCTION: No research exists evaluating the influences of specific variables
      such as obturation length, radiodensity, or the presence of voids on
      interpretation of periradicular area. The purpose of this study was to evaluate
      the effects of obturation length, radiodensity, and the presence of voids on the
      radiographic interpretations of periapical areas. METHODS: In a Web-based survey,
      3 test image groups of variable obturation lengths, radiodensities, and numbers
      of voids were presented to observers for evaluation of the periapical areas.
      Intracanal areas of the images were altered by using Adobe Photoshop to create 3
      test image groups. Each observer reviewed 2 control images and 1 image from each
      test image group. Responses were recorded in a 5-point Likert-type scale. Within
      each test image group, the periapical areas were identical. Kruskal-Wallis, Mann
      Whitney U, and Cliff's delta statistical tests were used to analyze results.
      RESULTS: A total of 748 observer responses were analyzed. Significant differences
      (P <= .01) in the median Likert-type scale responses were identified between the
      following paired groups: 3 mm short and 1 mm short, 3 mm short and flush, lower
      radiodensity and higher radiodensity, lower radiodensity and intermediate
      radiodensity, no voids and several voids, and several voids and single void.
      Effect sizes ranged from 0.19 to 0.41. CONCLUSIONS: Significant differences were
      noted within all 3 test image groups: length, radiodensity, and presence of
      voids. Length of obturation had the largest effect on interpretation of the
      periapical area, with the 3 mm short radiographic obturation length image
      interpreted less favorably.

PMID- 29061354
TI  - Odontogenic Potential of Parathyroid Hormone-related Protein (107-111) Alone or
      in Combination with Mineral Trioxide Aggregate in Human Dental Pulp Cells.
AB  - INTRODUCTION: Parathyroid hormone-related protein plays an important role in bone
      remodeling. Its N-terminal domain parathyroid hormone-related protein (107-111)
      is called osteostatin (OST). OST has demonstrated osteogenic potential when
      combined with biomaterials such as hydroxyapatite or bioceramics. However, the
      odontogenic potential of OST has not yet been reported. Therefore, the aim of
      this study was to determine whether OST has an odontogenic effect or a
      synergistic effect with mineral trioxide aggregate (MTA) in human dental pulp
      cells (hDPCs) and to examine the underlying signaling mechanisms involved in OST
      mediated odontogenic differentiation. METHODS: Viability of hDPCs on stimulation
      with OST or MTA was measured. Real-time polymerase chain reaction and Western
      blot analyses were performed to evaluate the expression levels of odontogenic
      markers and the activation of extracellular signal-regulated kinase (ERK). To
      evaluate mineralized nodule formation, alkaline phosphatase (ALP) staining and
      alizarin red S staining were performed. Combined effects of OST and MTA were
      evaluated. RESULTS: OST promoted odontogenic differentiation, as evidenced by the
      formation of mineralized nodules, induction of ALP activity, and upregulation of
      odontogenic markers (dentin sialophosphoprotein, dentin matrix protein-1, and
      ALP). Phosphorylation of ERK was increased by OST. However, ERK inhibitor (U0126)
      inhibited the increase in dentin sialophosphoprotein and dentin matrix protein-1
      expression and mineralization induced by OST. A combination of MTA and OST
      upregulated odontogenic differentiation-associated gene expression and calcium
      nodule mineralization in hDPCs compared with MTA alone. CONCLUSIONS: The present
      study revealed that OST can promote odontogenic differentiation and
      mineralization through activating the ERK signaling pathway. A combination of MTA
      and OST showed a synergistic effect compared with MTA alone in hDPCs.

PMID- 29061355
TI  - Influence of Endodontic Treatment and Retreatment on the Fatigue Failure Load,
      Numbers of Cycles for Failure, and Survival Rates of Human Canine Teeth.
AB  - INTRODUCTION: This study evaluated the effects of endodontic treatment and
      retreatment on the fatigue failure load, numbers of cycles for failure, and
      survival rates of canine teeth. METHODS: Sixty extracted canine teeth, each with
      a single root canal, were selected and randomly divided into 4 groups (n = 15):
      untreated, teeth without endodontic intervention; prepared, teeth subjected only
      to rotary instrumentation; filled, teeth receiving complete endodontic treatment;
      and retreated, teeth retreated endodontically. After the different endodontic
      interventions, the specimens were subjected to fatigue testing by the stepwise
      method: 200 N (* 5000 load pulses), 300 N, 400 N, 500 N, 600 N, 800 N, and 900 N
      at a maximum of 30,000 load pulses each or the occurrence of fracture. Data from
      load to failure and numbers of cycles for fracture were recorded and subjected to
      Kaplan-Meier and Log Rank tests (P < .05), in addition to Weibull analysis. The
      fractures of the specimens were classified as repairable or catastrophic.
      RESULTS: The retreated, filled, and untreated groups presented statistically
      significantly higher fatigue failure loads and numbers of cycles for failure than
      did the prepared group. Weibull analysis showed no statistically significant
      difference among the treatments for characteristic load to failure and
      characteristic number of cycles for failure, although, for number of cycles, a
      higher Weibull modulus was observed in filled and retreated conditions. The
      predominant mode of failure was catastrophic. CONCLUSION: Teeth subjected to
      complete endodontic treatment and retreatment behaved similarly in terms of
      fatigue failure load and number of cycles to failure when compared with untreated
      teeth.

PMID- 29061357
TI  - Saving Natural Teeth: Intentional Replantation-Protocol and Case Series.
AB  - INTRODUCTION: Intentional replantation is a reliable and predictable treatment
      for cases in which nonsurgical endodontic retreatment failed or is impractical
      and endodontic surgery is hampered because of anatomic limitations. METHODS AND
      RESULTS: This article presents a protocol for intentional replantation
      illustrated with some interesting cases. The cases presented here are from
      patients (average age, 61 years) with no contributing medical history. The cases
      are molars with previous failed endodontic treatment/retreatment and diagnosed
      with apical periodontitis. Treatment procedures included atraumatic extractions
      with minimal manipulations of the periodontal ligament, followed by root-end
      resection, root-end preparation with ultrasonic tips, root-end fill with
      bioceramic cement, and rapid tooth replacement into the socket. Granulomatous
      tissue was gently curetted when applicable. All procedures were performed under
      the microscope. CONCLUSIONS: Intentional replantation with careful case selection
      may be considered as a last option for preserving hopeless teeth. Atraumatic
      extraction by using state-of-the-art equipment, instruments, and materials,
      minimal extra-alveolar time, and maintaining an aseptic technique are key factors
      for success.

PMID- 29061356
TI  - Clindamycin-modified Triple Antibiotic Nanofibers: A Stain-free Antimicrobial
      Intracanal Drug Delivery System.
AB  - INTRODUCTION: A biocompatible strategy to promote bacterial eradication within
      the root canal system after pulpal necrosis of immature permanent teeth is
      critical to the success of regenerative endodontic procedures. This study sought
      to synthesize clindamycin-modified triple antibiotic (metronidazole,
      ciprofloxacin, and clindamycin [CLIN]) polymer (polydioxanone [PDS]) nanofibers
      and determine in vitro their antimicrobial properties, cell compatibility, and
      dentin discoloration. METHODS: CLIN-only and triple antibiotic CLIN-modified
      (CLIN-m, minocycline-free) nanofibers were processed via electrospinning.
      Scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR), and
      tensile testing were performed to investigate fiber morphology, antibiotic
      incorporation, and mechanical strength, respectively. Antimicrobial properties of
      CLIN-only and CLIN-m nanofibers were assessed against several bacterial species
      by direct nanofiber/bacteria contact and over time based on aliquot collection up
      to 21 days. Cytocompatibility was measured against human dental pulp stem cells.
      Dentin discoloration upon nanofiber exposure was qualitatively recorded over
      time. The data were statistically analyzed (P < .05). RESULTS: The mean fiber
      diameter of CLIN-containing nanofibers ranged between 352 +/- 128 nm and 349 +/-
      128 nm and was significantly smaller than PDS fibers. FTIR analysis confirmed the
      presence of antibiotics in the nanofibers. Hydrated CLIN-m nanofibers showed
      similar tensile strength to antibiotic-free (PDS) nanofibers. All CLIN-containing
      nanofibers and aliquots demonstrated pronounced antimicrobial activity against
      all bacteria. Antibiotic-containing aliquots led to a slight reduction in dental
      pulp stem cell viability but were not considered toxic. No visible dentin
      discoloration upon CLIN-containing nanofiber exposure was observed. CONCLUSIONS:
      Collectively, based on the remarkable antimicrobial effects, cell-friendly, and
      stain-free properties, our data suggest that CLIN-m triple antibiotic nanofibers
      might be a viable alternative to minocycline-based antibiotic pastes.

PMID- 29061358
TI  - A Systematic Review of the Survival of Teeth Intentionally Replanted with a
      Modern Technique and Cost-effectiveness Compared with Single-tooth Implants.
AB  - INTRODUCTION: The aim of this study was to investigate the survival rate of teeth
      intentionally replanted with a modern technique and to compare their cost
      effectiveness with that of single-tooth implants. MATERIALS AND METHODS: Four
      databases were systematically searched for articles that met inclusion criteria
      published between January 1966 and February 2017. Overall survival rate of
      intentional replantation was determined through a meta-analysis using a random
      effects model. Cost of different procedures was determined from the 2016 American
      Dental Association Dental Fees Survey. Cost-effectiveness analysis was performed
      for different treatment modalities. RESULTS: Six studies met the inclusion
      criteria. Meta-analysis resulted in a survival rate of 89.1% (95% confidence
      interval, 83.8%-94.4%). Compared with a single-tooth implant, intentional
      replantation was more cost-effective even when custom post/core and crown are
      also needed. CONCLUSION: The meta-analysis revealed a high survival rate for
      intentional replantation. Although the survival rate of implants is higher,
      intentional replantation is a more cost-effective treatment modality. Intentional
      replantation should be a treatment option discussed with patients, especially
      because an implant can still be placed if intentional replantation is
      unsuccessful.

PMID- 29061359
TI  - Comparative Evaluation of Postoperative Pain and Success Rate after Pulpotomy and
      Root Canal Treatment in Cariously Exposed Mature Permanent Molars: A Randomized
      Controlled Trial.
AB  - INTRODUCTION: The aim of this study was to compare postoperative pain and success
      rate following pulpotomy and root canal treatment. METHODOLOGY: Fifty-four
      permanent teeth with carious exposures were randomly divided equally into 2
      groups. Mineral trioxide aggregate pulpotomy was performed in the experimental
      group and root canal treatment was performed in the control group, using
      standardized protocols. The treated teeth were restored with base of glass
      ionomer cement followed by composite restoration. Pain was recorded every 24
      hours for 7 days after intervention. Clinical and radiographic evaluations were
      done every 3 months for 18 months. The data collected were statistically
      analyzed. RESULTS: At the end of follow-up, overall success rate was 85% in the
      pulpotomy group and 87.5% in the root canal treatment group (P > .05).
      Significant difference in pain incidence and pain reduction was found between the
      2 groups (P < .05), with lower scores reported in the pulpotomy group.
      CONCLUSION: Pulpotomy can be an alternative treatment for management of
      symptomatic permanent teeth with deep caries lesions.

PMID- 29061361
TI  - Reply.

PMID- 29061360
TI  - Ovarian hyperstimulation syndrome induced by hormone therapy for breast cancer
      treatment.

PMID- 29061362
TI  - Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and
      anorexia.
AB  - The objective of this study was to evaluate whether aprepitant in addition to 5
      HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and
      vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate
      the relationship between in vivo kinetics of plasma substance P and these adverse
      events. Patients with malignant lymphoma who received CHOP chemotherapy or THP
      (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after
      the start of chemotherapy. With the first course of chemotherapy, all patients
      received only granisetron on day1 as an antiemetic. Patients who experienced
      nausea, vomiting, or anorexia exceeding grade 1 in the first course received
      aprepitant for 3 days in addition to granisetron with the second course of CHOP
      chemotherapy. Plasma substance P concentrations at 24 and 72 hours after
      chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting,
      or anorexia was observed with the first course in 7 of 19 patients. During the
      second course with aprepitant, no patients experienced vomiting, and the toxicity
      grade of nausea, vomiting, or anorexia was decreased compared with those in the
      first course. Substance P concentrations showed no differences after
      chemotherapy, in patients with nausea, vomiting, or anorexia and in patients
      without. The addition of aprepitant to 5-HT3 receptor antagonist appears
      effective for CINV or anorexia for patients who received CHOP chemotherapy.

PMID- 29061364
TI  - Inflammatory microglia are glycolytic and iron retentive and typify the microglia
      in APP/PS1 mice.
AB  - Microglia, like macrophages, can adopt inflammatory and anti-inflammatory
      phenotypes depending on the stimulus. In macrophages, the evidence indicates that
      these phenotypes have different metabolic profiles with lipopolysaccharide (LPS)-
      or interferon-gamma (IFNgamma)-stimulated inflammatory cells switching to
      glycolysis as their main source of ATP and interleukin-4 (IL-4)-stimulated cells
      utilizing oxidative phosphorylation. There is a paucity of information regarding
      the metabolic signatures of inflammatory and anti-inflammatory microglia. Here,
      we polarized primary microglia with IFNgamma and show that the characteristic
      increases in tumor necrosis factor-alpha (TNFalpha) and nitric oxide synthase 2
      (NOS2) were accompanied by increased glycolysis and an increase in the expression
      of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3, an enzyme that
      plays a significant role in driving glycolysis. These changes were associated
      with increased expression of ferritin and retention of iron in microglia.
      Significantly, retention of iron in microglia increased TNFalpha expression and
      also increased glycolysis suggesting that increased intracellular iron
      concentration may drive the metabolic and/or inflammatory changes. Analysis of
      microglia prepared from wildtype mice and from transgenic mice that overexpress
      amyloid precursor protein (APP) and presenilin 1 (PS1; APP/PS1) revealed genotype
      related increases in glycolysis, accompanied by increased PFKFB3, and an increase
      in the expression of ferritin. The data indicate a distinct metabolic signature
      of inflammatory microglia from APP/PS1 mice that are also distinguishable by
      their iron handling profiles.

PMID- 29061363
TI  - Impact of developmental exposure to methylphenidate on rat brain's immune
      privilege and behavior: Control versus ADHD model.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most prevalent childhood
      mental disorders that often persists into adulthood. Moreover, methylphenidate
      (MPH) is the mainstay of medical treatment for this disorder. Yet, not much is
      known about the neurobiological impact of MPH on control versus ADHD conditions,
      which is crucial to simultaneously clarify the misuse/abuse versus therapeutic
      use of this psychostimulant. In the present study, we applied biochemical and
      behavioral approaches to broadly explore the early-life chronic exposure of two
      different doses of MPH (1.5 and 5 mg/kg/day) on control and ADHD rats (Wistar
      Kyoto and Spontaneously Hypertensive rats, respectively). We concluded that the
      higher dose of MPH promoted blood-brain barrier (BBB) permeability and elicited
      anxiety-like behavior in both control and ADHD animals. BBB dysfunction triggered
      by MPH was particularly prominent in control rats, which was characterized by a
      marked disruption of intercellular junctions, an increase of endothelial
      vesicles, and an upregulation of adhesion molecules concomitantly with the
      infiltration of peripheral immune cells into the prefrontal cortex. Moreover,
      both doses of MPH induced a robust neuroinflammatory and oxidative response in
      control rats. Curiously, in the ADHD model, the lower dose of MPH (1.5 mg/kg/day)
      had a beneficial effect since it balanced both immunity and behavior relative to
      vehicle animals. Overall, the contrasting effects of MPH observed between control
      and ADHD models support the importance of an appropriate MPH dose regimen for
      ADHD, and also suggest that MPH misuse negatively affects brain and behavior.

PMID- 29061365
TI  - Rho-specific Guanine nucleotide exchange factors (Rho-GEFs) inhibition affects
      macrophage phenotype and disrupts Golgi complex.
AB  - Macrophages play crucial role in tissue homeostasis and the innate and adaptive
      immune response. Depending on the state of activation macrophages acquire
      distinct phenotypes that depend on actin, which is regulated by small GTPase
      RhoA. The naive M0 macrophages are slightly elongated, pro-inflammatory M1 are
      round and M2 anti-inflammatory macrophages are elongated. We showed previously
      that interference with RhoA pathway (RhoA deletion or RhoA/ROCK kinase
      inhibition) disrupted actin, produced extremely elongated (hummingbird)
      macrophage phenotype and inhibited macrophage movement toward transplanted
      hearts. The RhoA function depends on the family of guanine-nucleotide exchange
      factors (GEFs), which catalyze the exchange of GDP for GTP and activate RhoA that
      reorganizes actin cytoskeleton. Using actin staining, immunostaining, Western
      blotting, flow cytometry and transmission electron microscopy we studied how a
      direct inhibition of Rho-GEFs with Rhosin (Rho GEF-binding domain blocker) and
      Y16 (Rho GEF DH-PH domain blocker) affects M0, M1 and M2 macrophage phenotypes.
      We also studied how Rho-GEFs inhibition and RhoA deletion affects organization of
      Golgi complex that is crucial for normal macrophage functions such as
      phagocytosis, antigen presentation and receptor recycling. We found that GEFs
      inhibition differently affected M0, M1 and M2 macrophages phenotype and that GEFs
      inhibition and RhoA deletion both caused changes in the ultrastructure of the
      Golgi complex. These results suggest that actin/RhoA- dependent shaping of
      macrophage phenotype has different requirements for activity of RhoA/GEFs pathway
      in M0, M1 and M2 macrophages, and that RhoA and Rho-GEFs functions are necessary
      for the maintenance of actin-dependent organization of Golgi complex.

PMID- 29061368
TI  - Dermoscopic technique for the evaluation of the nail unit.

PMID- 29061366
TI  - The additional oxygen as a carrier gas during long-duration sevoflurane exposure
      ameliorate the neuronal apoptosis and improve the long-term cognitive function in
      neonatal rats.
AB  - The effects of the oxygen concentration as a carrier gas and long duration
      anesthesia exposure on neuroapoptosis and cognitive impairments in the developing
      brain are not fully understood. This study shows that long-duration sevoflurane
      anesthesia with or without additional oxygen induces neuroapoptosis and long-term
      cognitive dysfunction in neonatal rats. Seven-day-old rats were exposed to
      sevoflurane anesthesia for 2, 4, and 6 h with 21% or 30% oxygen. The control
      group received 21% oxygen alone for 6 h. Post-anesthesia blood gas analysis
      resulted in hypoxia and hypercapnia. Moreover, PO2 and base excess in the 30%
      oxygen group were significantly higher than the 21% oxygen group. The numbers of
      caspase-3-positive cells in both cortical layer 3 and the CA1 region in the
      hippocampus in the 6 h anesthesia exposure group with 21% oxygen were increased
      compared with the 6 h anesthesia exposure with 30% oxygen and control groups.
      Cognitive function was assessed in an additional group of rats, and the brains
      were stained for NeuN 6 weeks post-anesthesia. Although the Morris water maze
      task was acquired equally by all rats 3 weeks post-anesthesia, the escape latency
      was significantly longer in the 6 h sevoflurane with 21% oxygen group than the 6
      h with 30% oxygen groups 6 weeks post-exposure. No difference was found with
      regard to freezing time among the groups in the fear conditioning test. The
      number of NeuN-positive cells in the CA1 region of the hippocampus in the control
      group was increased compared with the other groups. These findings indicate that
      long-duration sevoflurane exposure with 30% oxygen as a carrier gas would
      ameliorate neuronal apoptosis and improve long-term cognitive function in
      neonatal rats.

PMID- 29061367
TI  - Gastrointestinal distribution of chicken gastrin-cholecystokinin family
      transcript expression and response to short-term nutritive state.
AB  - The related peptide hormones cholecystokinin (CCK) and gastrin are conserved
      throughout vertebrate clades and implicated in energy homeostasis. CCK is
      generally accepted as a satiety hormone in poultry, but the role of gastrin
      remains poorly studied. Functional dissection of these ligands is required to
      characterise the molecular control of growth & satiety in the domestic chicken,
      for which there is an increasingly pressing mandate. There are limited
      descriptions of physiological distributions for the two genes in birds, and these
      are mostly reliant on immunohistochemistry which can prove problematic due to the
      shared structure of the targets. Therefore, we have defined the tissue
      distributions of CCK and gastrin in the chicken, focussing on the
      gastrointestinal tract, by using transcript-dependent techniques to improve
      reliability by increasing specificity. Though considerably more highly expressed
      in the brain, gastrointestinal CCK transcripts were dispersed throughout the
      small intestine and particularly around the proximal ileum. Gastrin expression
      was strictly limited to the gastric antrum region of the intestinal tract, albeit
      very highly expressed. We demonstrate that CCK mRNA expression does not respond
      as expected for a short-term satiety hormone, and that the short-term response of
      gastrin expression is paradoxical compared to its role in mammals. These results
      partially corroborate previous peptide distribution studies and initiate
      exploration of the nutrient-responsive roles of these hormones in avian energy
      balance.

PMID- 29061369
TI  - Unsuspected Uterine Sarcoma in an Urban Hospital: Does Surgical Approach Matter?
AB  - STUDY OBJECTIVE: To compare the incidence of unsuspected uterine sarcoma based on
      surgical approach, open versus minimally invasive, for myomectomy and
      hysterectomy. DESIGN: Retrospective chart review of demographic data,
      preoperative characteristics, operative details, and pathology results from the
      electronic medical record (Canadian Task Force classification II-3). SETTING: A
      large, urban, academic medical center. PATIENTS: All women undergoing myomectomy
      or hysterectomy performed for a benign indication via a benign gynecologic
      surgical procedure between 2010 and 2014. MEASUREMENTS AND MAIN RESULTS: A total
      of 1959 myomectomies and hysterectomies were performed, among which 4 unsuspected
      uterine sarcomas were identified, for an incidence of 2.0 per 1000 cases. The
      incidence of sarcoma was similar in patients undergoing open abdominal surgery
      and those undergoing minimally invasive surgery (MIS) (3 in 743 [0.40%] vs. 1 in
      1216 [0.08%]; p = .16). The mean age, body mass index, and specimen weights were
      also similar in the 2 groups. Although more than one-quarter of all cases
      involved morcellation, the majority via power morcellation, no specimens with
      sarcoma were morcellated. CONCLUSION: The incidence of unsuspected uterine
      sarcoma during myomectomy or hysterectomy for benign indications is low at our
      institution, and is similar for open and MIS cases. Patients should be counseled
      on the risks and benefits of both open surgery and MIS approaches.

PMID- 29061370
TI  - STrategically Acquired Gradient Echo (STAGE) imaging, part II: Correcting for RF
      inhomogeneities in estimating T1 and proton density.
AB  - PURPOSE: To develop a method for mapping the B1 transmit (B1t) and B1 receive
      (B1r) fields from two gradient echo datasets each with a different flip angle and
      from these two images obtain accurate T1 and proton density (PD) maps of the
      brain. METHODS: A strategically acquired gradient echo (STAGE) data set is
      collected using two flip angles each with multiple echoes. The B1t field
      extraction was based on forcing cortical gray matter and white matter to have
      specific T1 values and fitting the resulting B1t field to a quadratic function.
      The B1r field extraction was based on synthesizing isointense images despite
      there being two or three tissue types present in the brain. This method was
      tested on 10 healthy volunteers and 20 stroke patients from data acquired at
      3.0Tesla. RESULTS: With the knowledge of the B1t and B1r fields, the uniformity
      of tissue T1 and PD maps was considerably improved. T1 values were measured for
      both the midbrain and basal ganglia and found to be in good agreement with the
      literature. DISCUSSION AND CONCLUSIONS: STAGE provides a practical way to assess
      the B1t and the B1r fields which can then be used to correct for spatial
      variations in the images.

PMID- 29061371
TI  - Puerarin acts on the skeletal muscle to improve insulin sensitivity in diabetic
      rats involving MU-opioid receptor.
AB  - Puerarin, a major active isoflavone extracted from the root of Pueraria lobate,
      significantly increases plasma beta-endorphin and insulin levels and improves
      impaired insulin signaling in diabetic animals. However, the target tissues and
      underlying mechanisms in and through which puerarin functions to ameliorating
      insulin resistance remains largely unclear. In this study, we showed that
      puerarin enhanced MU-opioid receptor expression and phosphorylation, and
      increased insulin-stimulated glucose transporter 4 translocation to the plasma
      membrane in the skeletal muscle of diabetic rats, which were recaptured by a
      direct application of puerarin in the palmitate-induced insulin-resistant L6
      myotubes. Naloxone, an antagonist of MU-opioid receptor, blocked these functions
      of puerarin. No beta-endorphin was detected either in the muscle of diabetic rats
      or in the palmitate-induced insulin-resistant L6 cells. Furthermore, we presented
      the evidence to show the interaction between MU-opioid receptor and insulin
      receptor substrate 1 in the muscle tissues and cells. These results suggested
      that puerarin improved insulin sensitivity in the skeletal muscle at least in
      part by its local effects involving MU-opioid receptor function.

PMID- 29061372
TI  - The relationship of snus use to diabetes and allied conditions.
AB  - A recent meta-analysis reported smoking to be associated with a 37% higher risk
      of type 2 diabetes in current smokers, rising to a 57% increase in heavy smokers,
      which declines on quitting. If the increase results from nicotine exposure, it is
      possible that using Swedish moist snuff ("snus"), which provides at least
      equivalent nicotine doses, might also increase diabetes risk. Following a recent
      publication reporting pooled results from five cohorts, we present a detailed
      meta-analysis of data from 18 studies. Based on covariate-adjusted estimates, no
      significant increased risk was seen in never smokers with RRs (95% CIs) of 1.08
      (0.86-1.34), 0.93 (0.79-1.11) and 1.05 (0.94-1.18) for current, former and ever
      snus users. Significant increases were also not seen in the whole population, the
      corresponding RR estimates being 1.18 (0.94-1.48), 0.69 (0.49-0.96) and 0.95
      (0.81-1.11). Nor was there an association of snus use with related endpoints,
      such as impaired glucose tolerance. However, dose-response analyses showed a
      relationship, with the highest levels of snus exposure associated with a diabetes
      RR of 1.65 (1.25-2.18) in never smokers. The evidence relating snus to type 2
      diabetes is somewhat limited, requiring further studies to confirm any possible
      relationship.

PMID- 29061373
TI  - Resolution of contradiction between in silico predictions and Ames test results
      for four pharmaceutically relevant impurities.
AB  - The ICH M7 Guideline requires low level control of mutagenic impurities in
      pharmaceutical products to minimize cancer risk in patients (ICHM7, 2014).
      Bacterial mutagenicity (Ames) data is generally used to determine mutagenic and
      possible carcinogenic potential of compounds. Recently, a publication on
      experiences of using two in silico systems to identify potentially mutagenic
      impurities highlighted the importance of performing a critical review of
      published Ames data utilized as part of a mutagenicity assessment of impurities
      (Greene et al., 2015). Four compounds (2-amino-5-hydroxybenzoic acid, 2-amino-3
      chlorobenzoic acid, methyl 2-amino-4-chlorobenzoate and 4-morpholinopyridine)
      reported mutagenic were identified in a two system in silico assessment and
      expert review of the structuresas non-mutagenic. Likely reasons for mutagenicity
      could not be identified and the purity of the compounds tested was proposed. In
      the current investigation, the purest available sample of the four compounds was
      tested in an OECD-compliant Ames test. The compounds were all found to be non
      mutagenic. Possible reasons for the discrepancy between previously reported and
      current results are discussed. Additionally, important points to consider when
      conducting an expert review of available Ames data are provided particularly in
      cases where reported Ames results are discrepant with a two system in silico
      assessment.

PMID- 29061375
TI  - Evaluation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Mutation
      Detection.
AB  - The efficiency of a novel targeted next-generation sequencing (NGS) test, the
      Devyser BRCA kit, for a comprehensive analysis of all 48 coding exons of the high
      risk breast/ovarian cancer susceptibility genes BRCA1 and BRCA2 has been
      assessed. The new assay intended to detect nucleotide substitutions, small
      deletions/insertions, and large deletions/duplications. To document the false
      negative and false-positive rates of the NGS assay in the hands of end users, 48
      samples with previously identified 444 small variants and seven gross
      rearrangements were analyzed, showing 100% concordance with gold standards.
      Furthermore, all other 43 variants (42 single-nucleotide variation or
      insertion/deletion variation and one copy number variation, whose significance is
      or may be of clinical value), which were called by the NGS assay in a
      prospectively analyzed 179-sample set, were confirmed by Sanger sequencing or
      multiplex ligation probe amplification, according to their nature. We conclude
      that the Devyser BRCA kit performed satisfactorily for use in a clinical
      laboratory.

PMID- 29061374
TI  - Analytical Validation of a Next-Generation Sequencing Assay to Monitor Immune
      Responses in Solid Tumors.
AB  - We have developed a next-generation sequencing assay to quantify biomarkers of
      the host immune response in formalin-fixed, paraffin-embedded (FFPE) tumor
      specimens. This assay aims to provide clinicians with a comprehensive
      characterization of the immunologic tumor microenvironment as a guide for
      therapeutic decisions on patients with solid tumors. The assay relies on RNA
      sequencing (seq) to semiquantitatively measure the levels of 43 transcripts
      related to anticancer immune responses and 11 transcripts that reflect the
      relative abundance of tumor-infiltrating lymphocytes, as well as on DNA-seq to
      estimate mutational burden. The assay has a clinically relevant 5-day turnaround
      time and can be conducted on as little as 2.5 ng of RNA and 1.8 ng of genomic DNA
      extracted from three to five standard FFPE sections. The standardized next
      generation sequencing workflow produced sequencing reads adequate for clinical
      testing of matched RNA and DNA from several samples in a single run. Assay
      performance for gene-specific sensitivity, linearity, dynamic range, and
      detection threshold was estimated across a wide range of actual and artificial
      FFPE samples selected or generated to address preanalytical variability linked to
      specimen features (eg, tumor-infiltrating lymphocyte abundance, percentage of
      necrosis), and analytical variability linked to assay features (eg, batch size,
      run, day, operator). Analytical precision studies demonstrated that the assay is
      highly reproducible and accurate compared with established orthogonal approaches.

PMID- 29061376
TI  - Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple
      Melanomas and Association with MC1R Genotype: Findings from Molecular and
      Immunohistochemical Analysis.
AB  - Data on somatic heterogeneity and germline-somatic interaction in multiple
      primary melanoma (MPM) patients are limited. We investigated the mutational
      status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients
      and compared molecular and immunohistochemical findings. We further evaluated the
      association of somatic alterations with the germline MC1R genotype. Mutations in
      BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97),
      and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not
      differ across multiple melanomas (P = 0.85), whereas TERT promoter changes
      decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy
      of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients
      (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high
      rate of agreement between allele-specific TaqMan assay and immunohistochemistry
      in BRAFV600E detection (kappa = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%)
      presenting similar BRAF status. Germline MC1R variants were identified in 81.4%
      (35/43) of MPM patients with no association of MC1R genotype with somatic
      mutations or with intrapatient concordance of somatic mutational profile. Our
      results support the genetic diversity of multiple melanomas and show that somatic
      heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry
      may be useful as an initial screening test.

PMID- 29061379
TI  - Comparative effects of transforming growth factor beta isoforms on redox
      metabolism in thyroid cells.
AB  - INTRODUCTION: Transforming growth factor beta (TGF-beta) regulates thyroid
      function and growth. However, tumoral thyroid cells became resistant to this
      factor as they undifferentiated. Little is known about the effects of TGF-beta
      isoforms. We compared the role of redox metabolism in the response to TGF-beta
      isoforms between non tumoral and tumoral thyroid cells. METHODOLOGY AND RESULTS:
      Differentiated rat thyroid cells (FRTL-5) and human thyroid follicular carcinoma
      cells (WRO) were treated with the three isoforms of TGF-beta. TGF-beta isoforms
      stopped cell cycle at different steps; G1 for FRTL-5 and G2/M for WRO. The three
      isoforms decreased cell viability and increased ROS accumulation in both cell
      lines. These effects were more pronounced in FRTL-5 than in WRO, and the isoform
      beta1 was more potent in ROS production than the other two. TGF-beta isoforms
      decreased total glutathione, catalase expression and it activity in both cell
      lines. Only in FRTL-5 the lipid peroxidation was demonstrated. Moreover, TGF
      beta1 decreased glutathione peroxidase and mitochondrial superoxide dismutase
      mRNA expression and increased mitochondrial ROS in FRTL-5, but no in WRO.
      Pretreatment with selenium increased glutathione peroxidase activity and
      decreased ROS production in WRO treated with TGF-beta isoforms. Furthermore,
      selenium partially reversed the effect of TGF-beta isoforms on cell viability
      only in WRO cells. The knockdown of endogenous NOX4 significantly reduced the TGF
      beta1 effect on cell viability in WRO but no in FRTL-5. CONCLUSION: TGF-beta
      disrupted the redox balance and increased ROS accumulation in both cell lines.
      FRTL-5 cells showed reduced antioxidant capacity and had a greater sensitivity to
      TGF-beta isoforms, while WRO cells were more resistant. This observation provides
      new insights into the potential role of TGF-beta in the redox regulation of
      thyroid cells.

PMID- 29061378
TI  - Candidate recommendations for protein electrophoresis reporting from the Canadian
      Society of Clinical Chemists Monoclonal Gammopathy Working Group.
AB  - Protein electrophoresis is commonly used as an aid in the diagnosis of monoclonal
      gammopathies and is performed in many laboratories in Canada and throughout the
      world. However, unlike many other diagnostic tests, there is limited guidance for
      standardization and neither guidance nor specific recommendations for clinical
      reporting of serum (SPE) or urine (UPE) protein electrophoresis and immunotyping
      available in the literature. Therefore, a Canadian effort was undertaken to
      recommend standards that cover all aspects of clinical reporting with an ultimate
      goal towards reporting standardization. The Canadian Society of Clinical Chemists
      (CSCC) Monoclonal Gammopathy Interest Group (MGIG), which is composed of CSCC
      members with an interest in protein electrophoresis, has formed a Monoclonal
      Gammopathy Working Group (MGWG) to take initial steps towards standardization of
      SPE, UPE and immunotyping. Candidate standardization recommendations were
      developed, discussed and voted upon by the MGWG. Candidate recommendations that
      achieved 90% agreement are presented as consensus recommendations.
      Recommendations that did not achieve 90% consensus remain candidate
      recommendations and are presented with accompanying MGWG discussion. Eleven
      consensus recommendations along with candidate recommendations for nomenclature,
      protein fraction reporting, test utilization, interference handling and
      interpretive reporting options are presented.

PMID- 29061377
TI  - A cyclo-trimer of acetonitrile combining fluorescent property with ability to
      induce osteogenesis and its potential as multifunctional biomaterial.
AB  - : A biomaterial combining fluorescent property with ability to induce
      osteogenesis can serve as an ideal multifunctional scaffold in bone tissue
      engineering. However, the frequently used fluorescent agents can only serve as
      imaging probes. The polymer or oligomer with a conjugated system containing
      nitrogen atoms will fulfill these criteria. In this study, a cyclo-trimer of
      acetonitrile is synthesized using a facile method, which is proved to be 4-amino
      2,6-dimethylpyrimidine. The cyclo-trimer of acetonitrile demonstrates strong
      intrinsic photoluminescence and has the potential for in vivo imaging. The cyclo
      trimer of acetonitrile shows no toxicity both in vitro and in vivo. Moreover, the
      cyclo-trimer of acetonitrile significantly promotes the osteogenesis of SaOS-2
      cells by improving alkaline phosphatase activity, collagen type I and osteocalcin
      expression, as well as expressions of osteoblastic genes, and enhances the matrix
      mineralization of rBMSCs. Thus, the cyclo-trimer of acetonitrile synthesized in
      present study illustrates the employment of this kind multifunctional biomaterial
      in bone tissue engineering and may offer great potential in biomedical
      applications where bioimaging and osteogenesis are both required. STATEMENT OF
      SIGNIFICANCE: A conjugated cyclo-trimer of acetonitrile combining intrinsic
      fluorescent property with ability to induce osteogenesis was reported. Different
      from the traditional fluorescent dye or quantum dots, which are just "imaging
      agents", the cyclo-trimer of acetonitrile can serve as a multifunctional
      biomaterial and offer great potential in biomedical applications where bioimaging
      and osteogenesis are both required. To our best knowledge, the fluorescent
      property, especially fluorescent property in vivo and the ability of this
      molecule to induce osteogenesis have not been reported before. Our work
      illustrates the employment of this kind multifunctional biomaterial in bone
      tissue engineering and will highlight the importance of multifunctional
      biomaterial in biomedical applications.

PMID- 29061380
TI  - Influence of cervical margin relocation (CMR) on periodontal health: 12-month
      results of a controlled trial.
AB  - OBJECTIVES: The concept of Cervical Margin Relocation (CMR) consists on placing a
      base layer of direct resin composite to elevate supra-gingivally the proximal
      indirect bonded restorations. The aims of this clinical study were to evaluate 1.
      Bleeding on Probing (BoP) on posterior indirect restorations with one
      interproximal margin relocated cervically, and 2. possible correlation between
      depth of the interproximal margins and BoP. METHODS: CMR (Group 1) and shoulder
      preparations (Group 2) were performed in 35 posterior teeth and evaluated after
      12 months (T12). Cavities' margins were placed below the Cemento-Enamel-Junction
      (CEJ). CMR was applied in one interproximal box-slot preparation using G-Premio
      Bond, for dentin hybridization, and universal flow resin composite (GC Co. Tokyo,
      Japan). Pressed lithium disilicate crowns (LS2) (LiSi Press, GC Co. Tokyo, Japan)
      were made and placed with proprietary luting material. At baseline and after 12
      months, clinical surrogate parameters were assessed; and measurements were
      recorded for the restorative margin position in relation to margo gingivae by
      probing, and radiographically, the distance from the bone crest was calculated
      (in mm). Statistical analysis was performed. RESULTS: CMR was associated with
      statistically significant increased BoP scores compared to shoulder preparation
      at T12 (53.0% vs. 31.5% per site, respectively) (p=0.10). Gingival Index (GI) and
      Plaque Index (PI) were not statistically different between both groups. The
      linear distance between the bone crest and the restorative margin was 2mm in 13
      out of 19 experimental sites of Group 1, and 6 out of 11 of Group 2. CONCLUSIONS:
      Higher incidence of BoP can be expected around teeth treated with the concept of
      CMR and in coincidence with deep margins placed at or closer than 2mm from the
      bone crest. CLINICAL SIGNIFICANCE: CMR is a clinically sensitive-technique,
      especially when performed on deep subgingival margins.

PMID- 29061381
TI  - Alcohol representations are socially situated: An investigation of beverage
      representations by using a property generation task.
AB  - Previous research suggests that people's representations of alcoholic beverages
      play an important role in drinking behavior. However, relatively little is known
      about the contents of these representations. Here, we introduce the property
      generation task as a tool to explore these representations in detail. In a
      laboratory study (N = 110), and a bar field-study (N = 56), participants listed
      typical properties of alcoholic beverages, sugary beverages, and water. Each of
      these properties was then categorized using a previously developed, hierarchical
      coding scheme. For example, the property "sweet" was categorized as referring to
      "taste", which falls under "sensory experience", which falls under "consumption
      situation". Afterwards, participants completed measures of drinking behavior and
      alcohol craving. Results showed that alcoholic beverages were strongly
      represented in terms of consumption situations, with 57% and 69% of properties
      relating to consumption in the laboratory and the bar study, respectively.
      Specifically, alcoholic beverages were more strongly represented in terms of the
      social context of consumption (e.g., "with friends") than the other beverages. In
      addition, alcoholic beverages were strongly represented in terms of sensory
      experiences (e.g. "sweet") and positive outcomes (e.g. "creates fun"), as were
      the sugary beverages and water. In Study 1, the extent to which alcoholic
      beverages were represented in terms of social context was positively associated
      with craving and regularly consuming alcohol. The property generation task
      provides a useful tool to access people's idiosyncratic representations of
      alcoholic beverages. This may further our understanding of drinking behavior, and
      help to tailor research and interventions to reduce drinking of alcoholic and
      other high-calorie beverages.

PMID- 29061383
TI  - Release of soluble and vesicular purine nucleoside phosphorylase from rat
      astrocytes and microglia induced by pro-inflammatory stimulation with
      extracellular ATP via P2X7 receptors.
AB  - Purine nucleoside phosphorylase (PNP), a crucial enzyme in purine metabolism
      which converts ribonucleosides into purine bases, has mainly been found inside
      glial cells. Since we recently demonstrated that PNP is released from rat C6
      glioma cells, we then wondered whether this occurs in normal brain cells. Using
      rat primary cultures of microglia, astrocytes and cerebellar granule neurons, we
      found that in basal condition all these cells constitutively released a
      metabolically active PNP with Km values very similar to those measured in C6
      glioma cells. However, the enzyme expression/release was greater in microglia or
      astrocytes that in neurons. Moreover, we exposed primary brain cell cultures to
      pro-inflammatory agents such as lipopolysaccharide (LPS) or ATP alone or in
      combination. LPS alone caused an increased interleukin-1beta (IL-1beta) secretion
      mainly from microglia and no modification in the PNP release, even from neurons
      in which it enhanced cell death. In contrast, ATP administered alone to glial
      cells at high micromolar concentrations significantly stimulated the release of
      PNP within 1 h, an effect not modified by LPS presence, whereas IL-1beta
      secretion was stimulated by ATP only in cells primed for 2 h with LPS. In both
      cases ATP effect was mediated by P2X7 receptor (P2X7R), since it was mimicked by
      cell exposure to Bz-ATP, an agonist of P2X7R, and blocked by cell pre-treatment
      with the P2X7R antagonist A438079. Interestingly, ATP-induced PNP release from
      glial cells partly occurred through the secretion of lysosomal vesicles in the
      extracellular medium. Thus, during inflammatory cerebral events PNP secretion
      promoted by extracellular ATP accumulation might concur to control extracellular
      purine signals. Further studies could elucidate whether, in these conditions, a
      consensual activity of enzymes downstream of PNP in the purine metabolic cascade
      avoids accumulation of extracellular purine bases that might concur to brain
      injury by unusual formation of reactive oxygen species.

PMID- 29061382
TI  - Daily distribution of free healthy school meals or food-voucher intervention?
      Perceptions and attitudes of parents and educators.
AB  - AIMS: To qualitatively evaluate the optimal intervention (food-voucher approach
      vs. free daily meal distribution), aimed at reducing food insecurity and
      promoting healthy eating among students attending public schools in
      socioeconomically disadvantaged areas. METHODS: We randomly assigned 34 schools
      to one of the two interventions: students in 17 schools received a daily lunch
      box and parents in the other 17 schools received a food voucher of equal value
      once a month. All students were offered the opportunity to participate. We
      conducted 30 focus groups in all participating schools (17 in the meal
      distribution and 13 in the food voucher schools). Eligible participants included
      parents (n = 106), educators (n = 66) and school principals (n = 34). We
      qualitatively evaluated their perceptions and attitudes towards the program.
      RESULTS: Important differences were observed between the two approaches, with
      more favourable perceptions being reported for the meal distribution approach.
      More specifically, social stigmatization was minimized in the meal distribution
      approach, through the participation of all students, compared with the food
      voucher participants who reported feelings of embarrassment and fear of
      stigmatization. Secondly, the meal distribution approach alleviated child food
      insecurity through the provision of the daily meal, while the food-voucher
      intervention helped manage household food insecurity, as vouchers were mainly
      used for purchasing food for family meals. Furthermore, the educational and
      experiential nature of the meal distribution approach intensified healthy eating
      promotion, while the food-voucher intervention was efficient mainly for conscious
      parents regarding healthy eating. CONCLUSIONS: The meal distribution intervention
      was considered more effective than the food-voucher one. Hence, for interventions
      aiming at tackling food insecurity of children and adolescents, public health
      focus could be oriented towards school-based in kind food assistance.

PMID- 29061384
TI  - Motoneuron degeneration in the trigeminal motor nucleus innervating the masseter
      muscle in Dystonia musculorum mice.
AB  - Dystonia musculorum (dt) mice, which have a mutation in the Dystonin (Dst) gene,
      are used as animal models to investigate the human disease known as hereditary
      sensory and autonomic neuropathy type VI. Massive neuronal cell death is
      observed, mainly in the peripheral nervous system (PNS) of dt mice. We and others
      have recently reported a histopathological feature of these mice that
      neurofilament (NF) accumulates in various areas of the central nervous system
      (CNS), including motor pathways. Although dt mice show motor disorder and growth
      retardation, the causes for these are still unknown. Here we performed
      histopathological analyses on motor units of the trigeminal motor nucleus (Mo5
      nucleus), because they are a good system to understand neuronal responses in the
      mutant CNS, and abnormalities in this system may lead to problems in mastication,
      with subsequent growth retardation. We report that motoneurons with NF
      accumulation in the Mo5 nuclei of DstGt homozygous mice express the stress
      induced genes CHOP, ATF3, and lipocalin 2 (Lcn2). We also show a reduced number
      of Mo5 motoneurons and a reduced size of Mo5 nuclei in DstGt homozygous mice,
      possibly due to apoptosis, given the presence of cleaved caspase 3-positive Mo5
      motoneurons. In the mandibular (V3) branches of the trigeminal nerve, which
      contains axons of Mo5 motoneurons and trigeminal sensory neurons, there was
      infiltration of Iba1-positive macrophages. Finally, we report atrophy of the
      masseter muscles in DstGt homozygous mice, which showed abnormal nuclear
      localization of myofibrils and increased expression of atrogin-1 mRNA, a muscle
      atrophy-related gene and weaker masseter muscle strength with uncontrolled muscle
      activity by electromyography (EMG). Taken together, our findings strongly suggest
      that mastication in dt mice is affected due to abnormalities of Mo5 motoneurons
      and masseter muscles, leading to growth retardation at the post-weaning stages.

PMID- 29061387
TI  - Adaptive coordination of working-memory and reinforcement learning in non-human
      primates performing a trial-and-error problem solving task.
AB  - Accumulating evidence suggest that human behavior in trial-and-error learning
      tasks based on decisions between discrete actions may involve a combination of
      reinforcement learning (RL) and working-memory (WM). While the understanding of
      brain activity at stake in this type of tasks often involve the comparison with
      non-human primate neurophysiological results, it is not clear whether monkeys use
      similar combined RL and WM processes to solve these tasks. Here we analyzed the
      behavior of five monkeys with computational models combining RL and WM. Our model
      based analysis approach enables to not only fit trial-by-trial choices but also
      transient slowdowns in reaction times, indicative of WM use. We found that the
      behavior of the five monkeys was better explained in terms of a combination of RL
      and WM despite inter-individual differences. The same coordination dynamics we
      used in a previous study in humans best explained the behavior of some monkeys
      while the behavior of others showed the opposite pattern, revealing a possible
      different dynamics of WM process. We further analyzed different variants of the
      tested models to open a discussion on how the long pretraining in these tasks may
      have favored particular coordination dynamics between RL and WM. This points
      towards either inter-species differences or protocol differences which could be
      further tested in humans.

PMID- 29061385
TI  - Modified single prolonged stress reduces cocaine self-administration during
      acquisition regardless of rearing environment.
AB  - Until recently, there were few rodent models available to study the interaction
      of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single
      prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis
      dysfunction and alters psychostimulant self-administration. Other stressors, such
      as isolation stress, also alter psychostimulant self-administration. However, it
      is currently unknown if isolation housing combined with SPS can alter the
      acquisition or maintenance of cocaine self-administration. The current study
      applied modified SPS (modSPS; two hours restraint immediately followed by cold
      swim stress) to rats raised in an isolation condition (Iso), enrichment condition
      (Enr), or standard condition (Std) to measure changes in cocaine self
      administration and HPA markers. Regardless of rearing condition, rats exposed to
      modSPS had greater corticosterone (CORT) release and reduced cocaine self
      administration during initial acquisition compared to non-stressed controls. In
      addition, during initial acquisition, rats that received both Iso rearing and
      modSPS showed a more rapid increase in cocaine self-administration across
      sessions compared to Enr and Std rats exposed to modSPS. Following initial
      acquisition, a dose response analysis showed that Iso rats were overall most
      sensitive to changes in cocaine unit dose; however, modSPS had no effect on the
      cocaine dose response curve. Further, there was no effect of either modSPS or
      differential rearing on expression of glucocorticoid receptor (GR) in
      hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using
      modSPS in combination with Iso housing, this study identified unique
      contributions of each stressor to acquisition of cocaine self-administration.

PMID- 29061386
TI  - Principal component analysis and neural predictors of emotion regulation.
AB  - Reappraisal, a cognitive approach intended to alter an emotional response, is
      generally associated with prefrontal cortical recruitment and decreased limbic
      activity. However, the extent to which neurofunctional activity predicts
      successful reappraisal is unclear. During fMRI, 60 healthy participants completed
      a reappraisal paradigm, which included reappraising negative images to reduce
      emotional reactivity ('ReappNeg') and viewing negative images and experiencing
      the negative affect they evoke ('LookNeg'). After each trial, participants rated
      their emotional response on a Likert-type scale where higher values indicated
      more negative affect. Reappraisal ability was based on a difference value
      (DeltaReappNeg-LookNeg) such that negative values signified successful
      reappraisal ('SR'; n=38) and positive values, unsuccessful reappraisal ('USR';
      n=22). Neural activity based on ReappNeg-LookNeg conditions from 37 regions of
      interest encompassing cortical and limbic areas was submitted to Principal
      Component Analysis (PCA). Resulting PCA factors were submitted to discriminant
      function analysis to evaluate which factor(s) predicted SR and USR groups.
      Results showed a factor with high loadings for certain frontal areas (e.g., left
      dorsomedial prefrontal cortex) and limbic regions (e.g., bilateral amygdala)
      predicted 71.1% of cases in the SR group and 68.2% of cases in the USR group.
      Additionally, successful reappraisal corresponded with more activation in the
      factor with high loadings for frontal areas and less activity in the factor
      associated with limbic regions. Results are consistent with studies of individual
      differences where more prefrontal engagement and less limbic activity is
      associated with effectual reappraisal, but for the first time, a neural
      'signature' for successful reappraisal has been demonstrated.

PMID- 29061388
TI  - Is thoracoscopic-laparoscopic esophagectomy a better alternative to thoracoscopic
      esophagectomy?
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) is gaining rapid popularity as
      an alternative to conventional open esophagectomy. However, whether incorporating
      laparoscopy into MIE can further help the patients with esophageal cancer has
      rarely been studied. The aim of this study was to evaluate the short-term
      clinical efficacy of thoracoscopic-laparoscopic esophagectomy (TLE) compared with
      thoracoscopic esophagectomy (TE) in treating esophageal cancer. METHODS: From
      September 2014 to December 2016, a total of 131 patients with esophageal cancer
      who had consecutively undergone MIE were included in the analysis; of them, TLE
      was performed in 71 patients and TE in 60 patients. Characteristics and
      perioperative outcomes of all patients were collected and compared to determine
      differences between the 2 groups. RESULTS: Operation time (p = 0.172), chest
      drainage volume (p = 0.656), and pathologic staging (p = 0.671) were similar in
      the 2 groups. Compared with the TE approach, the TLE approach was associated with
      less blood loss during the operation (median, 100 vs 150 ml, p < 0.001), shorter
      chest drainage time (median, 2 vs 3 days, p < 0.001), a larger number of
      harvested lymph nodes (median, 24 vs 20, p < 0.001), and shorter postoperative
      hospital stay (median, 10 vs 11 days, p = 0.008). There was no significant
      difference between groups with regard to the major (grade >= III) and minor
      (grade < III) complications. CONCLUSIONS: TLE is a safe and effective alternative
      to TE. Patients undergoing TLE may benefit from less blood loss, a larger number
      of harvested lymph nodes and faster postoperative recovery. Additional randomized
      controlled trial with longer follow-up is needed.

PMID- 29061389
TI  - Mid-term graft patency of right versus left internal mammary artery as arterial
      conduit usage for left anterior descending artery revascularisation: Insights
      from a single-centre study of propensity-matched data.
AB  - BACKGROUND: Previous studies reported the strategy of in situ skeletonised right
      internal mammary artery (RIMA) grafting to the left anterior descending artery
      (LAD). However, few reports have focused on assessing RIMA graft patency rate
      after grafting to the LAD. This study aimed to assess mid-term graft patency of
      in situ skeletonised RIMA grafting to the LAD versus in situ skeletonised left
      internal mammary artery (LIMA) grafting to the LAD in a single-centre propensity
      matched study. MATERIALS AND METHODS: After propensity score matching, 185 pairs
      of patients who received first, scheduled, isolated off-pump coronary artery
      bypass grafting (OPCAB) surgery were assigned to either a RIMA group (patients
      who received retrosternal crossover in situ skeletonised RIMA-LAD grafting with
      additional conduits grafting) or a LIMA group (patients who received in situ
      skeletonised LIMA-LAD grafting with additional conduits grafting). The primary
      endpoint was mid-term internal mammary artery (IMA) graft failure after grafting
      to the LAD and was determined by coronary computed tomography angiography
      examination. The secondary endpoints were mid-term all-cause mortality and the
      composite mid-term clinical outcome. RESULTS: The graft patency rate of in situ
      skeletonised RIMA-LAD graft was not inferior to in situ skeletonised LIMA-LAD
      graft during a follow-up period of 36.6 +/- 12.1 months (97.2% vs. 96.6%, p =
      0.752). Kaplan-Meier curves showed a similar cumulative IMA graft failure between
      the two groups (chi2 = 0.092, Log-rank p = 0.762). And Cox regression analysis
      revealed that grouping was not an independent factor for follow-up IMA graft
      failure after grafting to the LAD (HR = 0.93, 95% CI: 0.68-2.13). Additionally,
      Kaplan-Meier curves showed similar cumulative survival free from adverse events
      between the two groups (chi2 = 2.365, p = 0.124, respectively). CONCLUSIONS:
      Revascularisation of the LAD using a skeletonised RIMA resulted in excellent mid
      term graft patency and clinical outcomes.

PMID- 29061390
TI  - Integrated geometric and mechanical analysis of an image-based lymphatic valve.
AB  - Lymphatic valves facilitate the lymphatic system's role in maintaining fluid
      homeostasis. Malformed valves are found in several forms of primary lymphoedema,
      resulting in incurable swelling of the tissues and immune dysfunction. Their
      experimental study is complicated by their small size and operation in low
      pressure and low Reynolds number environments. Mathematical models of these
      structures can give insight and complement experimentation. In this work, we
      present the first valve geometry reconstructed from confocal imagery and used in
      the construction of a subject-specific model in a closing mode. A framework is
      proposed whereby an image is converted into a valve model. An FEA study was
      performed to identify the significance of the shear modulus, the consequences of
      smoothing the leaflet surface and the effect of wall motion on valve behaviour.
      Smoothing is inherent to any analysis from imagery. The nature of the image,
      segmentation and meshing all cause attenuation of high-frequency features.
      Smoothing not only causes loss of surface area but also the loss of high
      frequency geometric features which may reduce stiffness. This work aimed to
      consider these effects and inform studies by taking a manual reconstruction and
      through manifold harmonic analysis, attenuating higher frequency features to
      replicate lower resolution images or lower degree-of-freedom reconstructions. In
      conclusion, two metrics were considered: trans-valvular pressure required to
      close the valve, DeltaPc, and the retrograde volume displacement after closure.
      The higher DeltaPc, the greater the volume of lymph that will pass through the
      valve during closure. Retrograde volume displacement after closure gives a metric
      of compliance of the valve and for the quality of the valve seal. In the case of
      the image-specific reconstructed valve, removing features with a wavelength
      longer than four MUm caused changes in DeltaPc. Varying the shear modulus from 10
      kPa to 60 kPa caused a 3.85-fold increase in the retrograde volume displaced. The
      inclusion of a non-rigid wall caused DeltaPc to increase from 1.56 to 2.52 cmH2O.

PMID- 29061391
TI  - Delivery of full predicted energy from nutrition and the effect on mortality in
      critically ill adults: A systematic review and meta-analysis of randomised
      controlled trials.
AB  - BACKGROUND: The amount of energy required to improve clinical outcomes in
      critically ill adults is unknown. OBJECTIVE: The aim of this systematic review
      and meta-analysis was to evaluate the impact of near target energy delivery to
      critically ill adults on mortality and other clinically relevant outcomes.
      DESIGN: Following PRISMA guidelines, MEDLINE, EMBASE, CINHAL and the Cochrane
      Library were searched for randomised controlled trials evaluating nutrition
      interventions in adult critical care populations. Included studies compared
      delivery of >=80% of predicted energy requirements (near target) from enteral
      and/or parenteral nutrition to <80% (standard care) and reported mortality. The
      quality of individual studies was assessed using the Cochrane 'Risk of Bias'
      tool, and the overall body of evidence using the GRADE approach. Fixed or random
      effect meta-analyses were used pending the presence of heterogeneity (I2 > 50%)
      when 3 or more studies reported the same outcome. Outcomes are presented as risk
      ratio (RR), 95% confidence interval (CI). RESULTS: Ten trials with 3155
      participants were included. Mortality was unaffected by the intervention (RR
      1.02, 95% CI 0.81, 1.27, p = 0.89, I2 = 25%). Evaluation of studies of higher
      quality and low risk of bias did not alter the mortality inference (3 trials, 352
      participants, RR 0.83, 95% CI 0.49, 1.40, p = 0.19, I2 = 39%). The quality of
      evidence across outcomes was very low. CONCLUSIONS: The delivery of near target
      energy when compared to standard care in adult critically ill patients was not
      associated with an effect on mortality. Because the quality of the evidence
      across outcomes was very low there is considerable uncertainty surrounding this
      estimate. This has implications for clinical utility of the evidence within the
      included reviews.

PMID- 29061392
TI  - A rabbit model of cerebral venous sinus thrombosis established by ferric chloride
      and thrombin injection.
AB  - OBJECTIVE: Cerebral venous sinus thrombosis (CVST) is a life-threatening disease
      with high misdiagnosis and mortality rates due to its complex etiology and
      unknown pathophysiology. The present study aimed to establish an animal model
      suitable for assessing the pathophysiology of CVST and develop treatment methods.
      METHODS: 40% ferric chloride (FeCl3) was administered for 5min followed by
      thrombin injection to induce superior sagittal sinus thrombosis (SSST). Digital
      subtraction angiography (DSA) was performed to ensure thrombosis and evaluate the
      recanalization rate 7days post-CVST. Neurological evaluation, Evans blue
      injection, 2,3,5-Triphenyltetrazolium chloride (TTC), and hematoxylin-eosin (H&E)
      staining were used to assess thrombosis and the accompanying brain parenchyma.
      RESULTS: SSST was detected in all model rabbits, with a thrombus recanalization
      rate of 10%. Brain infarction, hemorrhage, cell edema, and disruption of the
      blood-brain barrier (BBB) were also observed. CONCLUSION: The method of inducing
      cerebral venous sinus thrombosis by applying 40% FeCl3 and injecting thrombin is
      feasible and efficient. This experimental model mimics the pathogenesis and
      pathophysiology of actual CVST.

PMID- 29061393
TI  - Repulsive guidance molecule a suppresses angiogenesis after ischemia/reperfusion
      injury of middle cerebral artery occlusion in rats.
AB  - Repulsive guidance molecule a (RGMa) has now emerged as a molecule with
      pleiotropic roles, including repulsion, adhesion, migration and differentiation
      in the nervous system. In this study, adult male Sprague-Dawley (SD) rats
      received 90-min middle cerebral artery occlusion (MCAO) to observe RGMa/neogenin
      expression sites after ischemia/reperfusion injury and changes in angiogenesis
      after treatment with RNA interference using RGMa-specific recombinant adenovirus
      rAd5-shRNA-RGMa (rAd-shRGMa). To clarify how RGMa mediates angiogenesis, the RGMa
      function-blocking peptide six fibronectin type III (6FNIII) was also
      administered, and corresponding changes in vascular endothelial growth factor
      (VEGF), angiopoietin-2 (Ang2), angiopoietin-1 (Ang1), and brain derived
      neurotrophic factor (BDNF) were determined by western blotting. Both RGMa and its
      receptor neogenin were expressed in neurons and vessel endothelial cells after
      ischemia/reperfusion injury, and angiogenesis, coupled with functional recovery,
      was enhanced after RNA interference against RGMa compared with the vehicle
      groups. VEGF, Ang2, Ang1 and BDNF expression levels were significantly increased
      after intervention with rAd-shRGMa or 6FNIII. Thus, RGMa might suppress
      angiogenesis via VEGF, Ang2, Ang1 and BDNF after cerebral ischemia/reperfusion
      injury, which has therapeutic potential by reducing these endogenous detrimental
      mechanisms.

PMID- 29061394
TI  - JAK2/STAT3 pathway is involved in the protective effects of epidermal growth
      factor receptor activation against cerebral ischemia/reperfusion injury in rats.
AB  - Cerebral ischemia and reperfusion is a common pathophysiologic process, which is
      involved in stroke and brain trauma. Recent studies revealed that activating
      epidermal growth factor receptor (EGFR) ameliorates cerebral ischemia/reperfusion
      (I/R) injury, however, the precise mechanisms remain to be illuminated. In this
      study, the neurological behavior was evaluated by Longa score. The infarct volume
      was performed by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and the
      expression of p-EGFR, p-STAT3, connexin (Cx43), Bax and Bcl-2 were detected by
      Western blot. The neurological behavior and infarct volume were increased in rats
      with cerebral I/R injury. Epidermal growth factor (EGF) pretreatment
      significantly decreased neurological deficit and infarct volume. However, the
      antagonist of EGFR, AG1478 attenuated the EGF-induced reduction of neurological
      deficit and infarct volume. Moreover, the inhibitor of JAK2/STAT3, AG490
      undermined the protective effects stimulated by activating EGFR in rats with I/R
      injury. In addition, EGF pretreatment increased the expression of Bcl-2 and
      reduced the expression of Bax and Cx43, and the effects were abolished after
      using AG1478 and AG490. These findings implicate that JAK2/STAT3 pathway plays
      the vital role in I/R injury protection from activating EGFR. And the
      neuroprotective effects may associate with inhibiting the Cx43 expression and the
      inhibition of apoptosis.

PMID- 29061395
TI  - Large-scale cortical volume correlation networks reveal disrupted small world
      patterns in Parkinson's disease.
AB  - To date, the most frequently reported neuroimaging biomarkers in Parkinson's
      disease (PD) are direct brain imaging measurements focusing on local disrupted
      regions. However, the notion that PD is related to abnormal functional and
      structural connectivity has received support in the past few years. Here, we
      employed graph theory to analyze the structural co-variance networks derived from
      50 PD patients and 48 normal controls (NC). Then, the small world properties of
      brain networks were assessed in the structural networks that were constructed
      based on cortical volume data. Our results showed that both the PD and NC groups
      had a small world architecture in brain structural networks. However, the PD
      patients had a higher characteristic path length and clustering coefficients
      compared with the NC group. With regard to the nodal centrality, 11 regions,
      including 3 association cortices, 5 paralimbic cortices, and 3 subcortical
      regions were identified as hubs in the PD group. In contrast, 10 regions,
      including 7 association cortical regions, 2 paralimbic cortical regions, and the
      primary motor cortex region, were identified as hubs. Moreover, the regional
      centrality was profoundly affected in PD patients, including decreased nodal
      centrality in the right inferior occipital gyrus and the middle temporal gyrus
      and increased nodal centrality in the right amygdala, the left caudate and the
      superior temporal gyrus. In addition, the structural cortical network of PD
      showed reduced topological stability for targeted attacks. Together, this study
      shows that the coordinated patterns of cortical volume network are widely altered
      in PD patients with a decrease in the efficiency of parallel information
      processing. These changes provide structural evidence to support the concept that
      the core pathophysiology of PD is associated with disruptive alterations in the
      coordination of large-scale brain networks that underlie high-level cognition.

PMID- 29061397
TI  - Diabetes aggravates decreases in hippocalcin and parvalbumin expression in focal
      cerebral ischemia.
AB  - Hyperglycemia is a major risk factor for stroke and increases brain damage during
      ischemic stroke. Hyperglycemia increases the intracellular calcium concentration
      after ischemic injury, thereby triggering neuronal cell death. Calcium binding
      proteins, including hippocalcin and parvalbumin, are critical regulators of
      intracellular calcium levels. This study aimed to investigate whether
      hyperglycemic conditions affect hippocalcin and parvalbumin expression during
      ischemic brain injury. Male adult rats were treated intraperitoneally with
      streptozotocin (40mg/kg) to induce hyperglycemia. Four weeks later, cerebral
      ischemic injury was induced via surgical middle cerebral artery occlusion (MCAO).
      Cerebral cortex samples were collected 24h after MCAO. A proteomic approach
      showed that the protein levels of hippocalcin and parvalbumin were significantly
      decreased in streptozotocin-treated animals with MCAO injury compared to
      streptozotocin-treated animals and animals that underwent MCAO alone. Reverse
      transcription-PCR and Western blot analyses clearly confirmed the decreased
      levels of these proteins. These decreases indicate dysregulation of the
      intracellular calcium balance and induction of cell death. Thus, these results
      suggest that significantly decreased levels of hippocalcin and parvalbumin
      exacerbate neuronal cell death in diabetic animals with ischemic brain injury.

PMID- 29061396
TI  - Increased level of procalcitonin is associated with total MRI burden of cerebral
      small vessel disease in patients with ischemic stroke.
AB  - BACKGROUND: Procalcitonin (PCT) has been found to be associated with subclinical
      cerebrovascular damage. The relationship between PCT levels and cerebral small
      vessel disease (cSVD), especially cSVD burden, has not been fully understood.
      This study aimed to investigate the association between PCT levels and cSVD in
      patients with first-ever acute ischemic stroke or transient ischemic attack
      (TIA). METHODS: Two hundred and seventy-eight consecutive patients were
      prospectively recruited during Jan 2016 to Jun 2017. Serum PCT concentrations
      measurement was performed after admission. The presence and burden of cSVD was
      determined by magnetic resonance imaging (MRI). Multivariable logistic regression
      was used to assess whether serum PCT levels were associated with cSVD. RESULTS:
      The median PCT level was 0.042MUg/L (interquartile range, 0.025-0.065MUg/L).
      Univariable logistic regression analysis indicated that patients with PCT level
      in the top quartile, compared with the lowest quartile, were more likely to have
      silent lacunar infarctions [odds ratio (OR), 2.266; 95% confidence interval (CI)
      1.131-4.538, P=0.021], white matter lesions (OR, 1.793; 95% CI 1.029-3.574,
      P=0.047), high-grade enlarged perivascular spaces (OR, 8.061; 95% CI 3.599
      14.055, P=0.001) and increased total MRI cSVD burden (OR, 3.743; 95% CI 1.998
      7.008, P=0.002). These results persisted even after adjusting for potential
      confounders. CONCLUSIONS: This study demonstrated that elevated PCT levels might
      be associated with total MRI cSVD burden in patients with ischemic stroke or TIA.

PMID- 29061400
TI  - Felt needs of primary caregivers of individuals with schizophrenia: A study from
      South India.

PMID- 29061398
TI  - Endogenous pleiotrophin and midkine regulate LPS-induced glial responses.
AB  - Pleiotrophin (PTN) and Midkine (MK) are two growth factors that modulate
      neuroinflammation. PTN overexpression in the brain prevents LPS-induced
      astrocytosis in mice but potentiates microglial activation. The modest astrocytic
      response caused by a low dose of LPS (0.5mg/kg) is blocked in the striatum of MK
      /- mice whereas microglial response is unaffected. We have now tested the effects
      of an intermediate dose of LPS (7.5mg/kg) in glial response in PTN-/- and MK-/-
      mice. We found that LPS-induced astrocytosis is prevented in prefrontal cortex
      and striatum of both PTN-/- and MK-/- mice. Some of the morphological changes of
      microglia induced by LPS tended to increase in both genotypes, particularly in
      PTN-/- mice. Since we previously showed that PTN potentiates LPS-induced
      activation of BV2 microglial cells, we tested the activation of FYN kinase, a
      substrate of the PTN receptor RPTPbeta/zeta, and the subsequent ERK1/2
      phosphorylation on LPS and PTN-treated BV2 cells. LPS effects on BV2 cells were
      not affected by the addition of PTN, suggesting that PTN does not recruit the FYN
      MAP kinase signaling pathway in order to modulate LPS effects on microglial
      cells. Taking together, evidences demonstrate that regulation of astroglial
      responses to LPS administration are highly dependent on the levels of expression
      of PTN and MK. Further studies are needed to clarify the possible roles of
      endogenous expression of PTN and MK in LPS-induced microglial responses.

PMID- 29061401
TI  - "Musical Ear Syndrome"-Musical hallucinations in a patient with severe hearing
      loss-A report.

PMID- 29061399
TI  - [Lynch syndrome and endometrial cancer].
AB  - Lynch syndrome is a hereditary predisposition to many tumors, in the forefront of
      which endometrial cancer in women. It is related to the mutation of a mismatch
      repair gene, involved in DNA mismatch repair. This mutation leads to a loss of
      expression of the corresponding protein, and to genome instability in tumor
      cells. Cumulative risk at the age of 70 years is over 40 %. Endometrial cancers
      related to Lynch syndrome are most of the time sentinel (They reveal the
      predisposition in half of families.) and are characterized by young age at onset
      (before 60 years) and low body mass index compared with patients presenting
      sporadic tumors. Pathological tumor characteristics are debated but it seems to
      be two types of tumors according to age, older patients having standard tumors
      and younger ones more aggressive pattern. Endometrial cancers related to Lynch
      syndrome can be synchronous of ovarian cancer. Therapeutic management does not
      present any particularity. Conservative treatment can be considered more
      frequently due to young age of patients but has to respect usual guidelines.
      Prognosis of these tumors is controversial. Gynaecological screening, although
      its benefit has not been proved, appears crucial in this population, as well as
      prophylactic surgery, which remains the best prevention.

PMID- 29061402
TI  - Mental health survey of adult population in Kermanshah County, 2015: Preliminary
      report.
AB  - BACKGROUND: Policies for mental health care are improving in Iran and accurate
      data is needed. There is no population based study about mental health from West
      of Iran. METHODS: The study population was the entire adult (18 years old and
      above) inhabitants of Kermanshah county (the city and the related rural area).
      This population was 656683 from whom 83.6% lived in urban area and 16.4% lived in
      rural area. General health questionnaire (GHQ)-28 was completed by a randomly
      selected cluster sample (84.1% response rate)of urban and rural area of
      Kermanshah county, 2015. RESULTS: A positive result was achieved from 39.1% (out
      of 2102). It was not related to gender, age group, job or marital status but
      illiterate participants, and those with lower economic level had higher scores.
      CONCLUSION: A considerable proportion of Kermanshah inhabitants, were screened
      positive for general health problems.

PMID- 29061404
TI  - Two unusual cases of protracted inter-ictal delirium following electroconvulsive
      therapy.

PMID- 29061403
TI  - Neuroleptic malignant syndrome: A neuro-psychiatric emergency: Recognition,
      prevention, and management.
AB  - Neuroleptic Malignant Syndrome (NMS) is a life threatening complication of
      antipsychotic therapy. It is often assumed to be rare. Observations suggest that
      rather than overestimating its frequency, we are more likely to underestimate it
      (Pope et al., 1986). It is a rare but potentially fatal disorder characterized by
      four principal symptoms. These are mental status changes, muscle rigidity,
      hyperthermia, and autonomic dysfunction. The diagnosis of NMS often presents a
      challenge because several medical conditions generate similar symptoms. Although
      less common now than in the past, thanks to greater awareness, it remains a risk
      in susceptible patients receiving conventional or atypical neuroleptics. Reducing
      the risk factors, early recognition of suspected cases, and prompt management can
      significantly reduce morbidity and mortality of this dangerous condition.
      Collaboration between psychiatry and other medical specialities may be the key to
      a successful outcome.

PMID- 29061405
TI  - Role of Ketamine in Severe Depression with suicidal ideation - Insights from a
      Case Study.

PMID- 29061406
TI  - Dementia as a presenting symptom of HIV/AIDS: A patient report and review of the
      evidence.

PMID- 29061407
TI  - Primary psychosis with comorbid drug abuse and drug-induced psychosis: Diagnostic
      and clinical evolution at follow up.
AB  - The study reports a follow-up assessment of 48 patients with concomitant drug
      abuse at the first admission for psychosis. We focused on the diagnostic
      distinction between primary psychosis with concomitant drug abuse and drug
      induced psychosis, to observe whether the diagnoses are stable over time and
      whether the clinical course significantly differs. The study examined 25 primary
      psychotic disorder with comorbid drug abuse and 23 drug-induced psychotic
      disorder patients. Diagnostic and psychopathological assessments were made at
      baseline and at follow-up. Mean follow-up period was 4.96 years. Patients with
      comorbid Drug Abuse exhibited higher scores in the item Unusual Content of
      Thought at baseline than drug-induced psychotic disorder patients: 5.48 vs 4.39
      while the two patients groups did not differ in any of the BPRS items evaluated
      at follow-up. The primary psychosis with comorbid drug abuse and the substance
      induced psychosis groups were similar regarding diagnostic stability, and a
      diagnosis of schizophrenia at follow-up occurred similarly. There was no evidence
      that Drug Induced psychotic patients' symptoms tend to improve more after
      cessation of drug abuse. An earlier age of onset was found in primary psychotic
      patients, particularly for patients diagnosed as affected by schizophrenia at
      follow up. These results might reflect the uncertainty of the distinction between
      Primary and Drug Induced Psychosis and the difficulties in applying the DSM IV-TR
      criteria for diagnosing comorbid drug use disorders and psychotic disorders.

PMID- 29061408
TI  - Predictors of non-suicidal and suicidal self-injurious behaviours, among
      adolescents and young adults in urban India.
AB  - BACKGROUND: The complex intersections between non-suicidal self-injurious (NSSI)
      behaviours; like cutting, burning or self-hitting, and suicide attempts, are an
      important domain of enquiry among vulnerable adolescents and young adults. A
      cross-sectional survey in urban schools and colleges assessed the rates of self
      injurious behaviour among Indian adolescents and young adults. Predictors of NSSI
      and of self-injurious behaviours with associated suicidal intent, were also
      examined. PARTICIPANTS AND METHODS: The sample comprised 1571 male and female
      students, from 19 private and government aided high schools, pre-university
      colleges and undergraduate colleges in an urban city in South India. Participants
      completed the Functional Assessment of Self-Mutilation which assesses the
      methods, characteristics and functions of self-injurious acts in the past 12
      months. The measures of psychopathology included the Youth Self-Report and the
      Young-Adult Self-Report. RESULTS AND CONCLUSION: The results indicated that rate
      of NSSI was 33.8%, with minor forms of self-injury reported more often (19.4%)
      than the moderate/severe forms (14.6%). A smaller proportion (6.8%) reported self
      injurious acts with associated suicidal intent. Certain self-injury
      characteristics and levels of internalizing and externalizing problems
      differentiated self-injuring youth with and without suicidal intent. Logistic
      regression analyses identified predictors of any self-injurious behaviour and of
      self-injury associated with suicidal intent. The implications for assessment and
      intervention frameworks for self-injuring youth are discussed.

PMID- 29061409
TI  - Intolerance of uncertainty, depression, and anxiety: Examining the indirect and
      moderating effects of worry.
AB  - The present study sought to examine the indirect and moderating effects of worry
      between intolerance of uncertainty (IU) and symptoms of depression and anxiety.
      The study was a cross sectional study. Data were collected from 120 psychiatric
      patients, aged 22 to 37 years. A battery of self-report questionnaires was
      administered for tapping IU, worry, depression and anxiety symptoms. Results from
      indirect effects analyses revealed that even though IU, worry, depression, and
      anxiety symptoms correlated moderately with each other, worry carried a
      substantial proportion of variance in predicting symptoms of depression and
      anxiety. However, the relative effect was more pronounced for anxiety compared to
      depression symptoms. The results from hierarchical analyses supported the
      moderator role of worry. More specifically, a high level of worry enhanced the
      association between IU and symptoms of depression and anxiety. Given the
      potential for worry as a mechanism, and/or moderator between IU and symptoms of
      depression and anxiety, adults with a tendency to use this negative repetitive
      thought process (e.g. worry) may be at higher risk to develop psychological
      symptoms.

PMID- 29061410
TI  - Elevated serum adenosine deaminase levels in neuroleptic-naive patients with
      recent-onset schizophrenia.
AB  - The present study examined serum levels of adenosine deaminase (ADA), an
      adenosine metabolizing enzyme, in neuroleptic-naive patients with recent-onset
      schizophrenia and age-matched healthy comparison subjects. ADA levels were found
      to be higher among patients, and revealed a possible link between evening rise
      and severity of auditory hallucinations as well as morning rise and severity of
      avolition-apathy in patients with schizophrenia. These findings suggest the
      potential utility of serum ADA as a peripheral biomarker of schizophrenia.

PMID- 29061411
TI  - Benzodiazepine misuse: When shall we wake up?

PMID- 29061412
TI  - What predicts medical lethality of suicide attempts in Asian youths?
AB  - This study explores youth suicide attempts in Singapore using multiple databases
      of comprehensive archival records. Three years of medical records related to
      suicide attempters (N=666) who were admitted to the emergency department of a
      large teaching hospital in Singapore were subjected to retrospective analysis.
      Compared to other age groups, a peak in suicide attempts (n=207) was observed in
      youths aged between 15 and 24 years old (76.3% females; 23.7% males, mean
      age=19.30, SD=2.89). The model using recognized risk and protective factors was
      significant in predicting medical lethality, and correctly classified 62.8% of
      high lethality cases. Only resolution of precipitant made a unique statistical
      significant contribution. Analysis was separately conducted for males and
      females. Implications of the findings are discussed.

PMID- 29061413
TI  - Aggression in schools: Cyberbullying and gender issues.
AB  - Due to increasing internet and mobile penetration, children in India are at risk
      of cyberbullying. A survey of 174 middle graders in Delhi showed that, of total,
      8% indulged in cyberbullying and 17% reported being victimized by such acts.
      However, prevalence of in-person bullying, fighting and victimization by either
      was 16%, 12% and 17% respectively. Males were more likely to bully and fight in
      person than females. They were also more likely to be victims of both online and
      offline aggression. Interwoven modes of bullying along with safe use of
      technology need to be understood.

PMID- 29061414
TI  - Koro: Much more than just a culture bound syndrome.

PMID- 29061415
TI  - Antidepressant-related jitteriness syndrome in anxiety and depressive disorders:
      Incidence and risk factors.
AB  - INTRODUCTION: Jitteriness syndrome (JS) is a poorly understood but important
      adverse effect of antidepressant drugs. This study examined the incidence and
      pattern of antidepressant-related JS and its predictors. METHODS: 209 patients
      diagnosed with any anxiety or depressive disorder and started on mirtazapine,
      sertraline, desvenlafaxine, escitalopram or fluoxetine were assessed at baseline,
      after 2 weeks, and after 6 weeks with psychopathology rating scales and for
      predefined categories of JS. RESULTS: The incidence of JS during the 6-week study
      was 27.7%, but only 6.7% in first 2 weeks. JS rates were similar in anxiety and
      depressive disorders. Mirtazapine was associated with the lowest rate of 14.3%,
      and other antidepressants with rates of 23-34%. High dose antidepressant
      treatment was significantly associated with JS (OR, 2.68; 95% CI, 1.37-5.25). No
      other variable predicted JS. JS was associated with significantly higher
      objective ratings of psychopathology. DISCUSSION: We conclude that up to a
      quarter of patients may suffer JS during the first 6 weeks of antidepressant
      initiation; higher antidepressant dose is a risk factor.

PMID- 29061416
TI  - Prevalence of depression among middle aged women in the rural area of Kerala.
AB  - AIMS: The aim of this study was to determine the prevalence of Depression among
      women aged 40-60 years in the rural area of Kerala using Patient Health
      Questionnaire 9 (PHQ-9). SETTINGS AND DESIGN: Ambalappuzha is an area of rural
      background under the District of Alappuzha. The study was conducted by Preventive
      and Social Medicine department of Govt. T. D. Medical College, Kerala in
      collaboration with the department of Psychiatry with the help of Ambalappuzha
      health centre. METHODS AND MATERIAL: A cross-sectional survey was carried out
      among 594 women from 18 wards of Amabalappuzha North Panchayat using cluster
      sampling technique. Data on sociodemographic factors, health factors, and
      behavioral factors were collected from the women by investigator administered the
      semi-structured questionnaire. Patient Health Questionnaire9 (PHQ-9), was used
      for diagnosing Major Depression. RESULTS: The prevalence of Major Depression
      among middle aged women was 26.09% using the PHQ-9 diagnostic criteria and 24.2%
      using a PHQ-9 cut off score >= 10. With increasing age, there was an increasing
      trend in the prevalence of Depression up to the age of 55years followed by a
      small decline. A higher prevalence of Depression was observed among widows
      (43.37%), women not in a marital relation (41.38%), a woman with a history of
      postpartum Depression (OR 3.471), with peri-menopausal symptoms (40.28%, OR
      2.86). CONCLUSIONS: One fourth of the women screened positive for Depression in
      Ambalappuzha North Panchayat (26.09%). This study highlights the need for
      understanding the high prevalence and myriad determinants of depression among
      women living in villages.

PMID- 29061417
TI  - Bipolar disorder in Asia: Illness course and contributing factors.
AB  - BACKGROUND: Epidemiological studies analysing the course of Bipolar Disorder (BD)
      are relatively rare in the Asian context, contributing to the uncertainty
      regarding the prevalent course patterns and factors influencing such patterns.
      The current review identifies the regional characteristics of BD course patterns
      and the associated factors. METHODS: A review of the existing literature was done
      using 'PubMed' and 'Cochrane' databases which yielded 145 studies including those
      from all 48 Asian countries. Relevant discussions from the Western literature
      were incorporated. RESULTS: Regional and cross-national studies reveal a mania
      predominant course in BD in Asian countries. Prolonged depressive episodes and
      comorbid anxiety disorders worsen the course of BD-II. Certain risk factors such
      as the young age of onset and greater episode frequency are useful predictors of
      bipolar diatheses. Substance use disorder comorbidity is more prevalent in males
      whereas depression and suicidal behaviours are more frequent in females with BD.
      Comorbid anxiety and personality disorders also encumber the illness course.
      Logistic reasons and ignorance of side-effects were specifically associated with
      poor adherence. An 'eveningness' chronotype and poor sleep quality were
      associated with frequent recurrences. Seasonal patterns vary among men and women,
      especially for depressive episodes. LIMITATIONS: The effects of treatment and
      childhood BD course features were not discussed. CONCLUSIONS: There are region
      specific characteristics in bipolar illness course and factors influencing such
      course patterns compared to the rest of the World. Future research from Asia
      shall attempt to study the neurobiological underpinnings of such characteristics
      and plan appropriate strategies to address the same.

PMID- 29061418
TI  - Alcohol binge drinking in OCD: A compulsive ritualistic behaviour to counter
      magical thinking.

PMID- 29061419
TI  - Aripiprazole induced hypersexuality, when we should be cautious?

PMID- 29061420
TI  - Utility of lurasidone in bipolar disorder type IV patient-A case report.

PMID- 29061421
TI  - Examining the psychometric properties of the Hindi version of Family
      Accommodation Scale-Self-Report (FAS-SR).
AB  - CONTEXT: Family accommodation (FA) is the phenomenon whereby caregivers assist or
      facilitate rituals or behaviours related to obsessive compulsive disorder (OCD).
      There is a need for a self-rated instrument to assess this construct in resource
      strained clinical settings of India. AIM: To explore the factor structure of
      Hindi version of Family Accommodation Scale-Self Rated version (FAS-SR) and
      compare its validity with the gold standard Family Accommodation Scale
      Interviewer Rated (FAS-IR) scale. MATERIAL & METHODS: The Hindi version of FAS-SR
      scale and FAS-IR scale was applied on 105 caregivers of patients with OCD.
      RESULTS: The initial factor analysis yielded three-factor models with an
      eigenvalue of >1 and the total variance explained by these factors was 72.017%.
      The internal consistency of the 19-item scale was 0.93 indicating good inter-item
      correlation. There was a significant positive correlation between FAS-IR scale
      total score and all the factors of the FAS-SR Scale. The average measure ICC was
      0.889 with a 95% confidence interval from 0.783 to 0.981 (F (62,84)=37.547,
      p<001) indicating high degree of reliability between the Hindi version of FAS-SR
      and the FAS-IR scale. CONCLUSIONS: FAS-SR is a practical alternative to FAS-IR
      and has the potential to be used widely in an Indian setting.

PMID- 29061422
TI  - Involuntary admission and treatment experiences of persons with schizophrenia:
      Implication for the Mental Health Care Bill 2016.
AB  - BACKGROUND: Involuntary admission and treatment experiences may affect the
      attitude of patients toward subsequent treatment and further outcomes. This issue
      has received relatively less research attention in persons with schizophrenia
      from developing countries. METHODOLOGY: In this hospital based prospective
      observational study, involuntary admission, treatment and coercion experiences
      among 76 persons with schizophrenia, admitted under special circumstances of
      Mental Health Act -1987 were studied. Demographic, clinical and assessments
      related to coercion experiences were completed within 3days of admission. In 67
      subjects, a reassessment was done just before discharge. RESULTS: Mean (SD) age
      was 33.1 (+/-11.5) years, 47.8% (n=32) were males and 32.8% (n=22) were married.
      92.5% (n=62) had absent insight at admission. Mean CGI Severity score at
      admission was 6.27 (+/-0.53). Mean (SD) score on MacArthur Perceived Coercion
      Scale at admission was 4.04 (+/-1.61). This reduced to 2.43(+/-1.91) [p<0.001].
      This reduction correlated significantly with improvements in global functioning
      (r=-0.40, p <0.001), insight level(r=0.26, p<0.001) and as well as symptom
      severity(r=0.36, p<0.001). At discharge, 70% (n=47) patients reported that their
      involuntary admission was justified. CONCLUSION: Perceived coercion in
      schizophrenia though common clinical phenomena, it is a dynamic state which
      reduces over course of treatment. At Discharge, majority reported that their
      admission was justified, even though they were admitted involuntarily. The study
      underlines the need for a standardized rule of conduct based coercive practice in
      psychiatry.

PMID- 29061423
TI  - Neuropsychological profile of schizophrenia with and without obsessive compulsive
      disorder.
AB  - Neuropsychological profile of schizophrenia with obsessive compulsive disorder
      (OCD) in comparison with that of schizophrenia without OCD is understudied and
      the results are inconsistent. We hypothesize that patients having schizophrenia
      with OCD ('schizo-obsessive disorder') may have unique neuropsychological
      deficits in comparison with those with schizophrenia alone, particularly with
      respect to executive functions. Thirty patients with schizo-obsessive disorder
      and 30 individually matched patients with schizophrenia without any obsessive
      compulsive symptoms formed the sample of the study. Neuropsychological assessment
      included tests for attention, executive functions and memory. Patients with
      schizo-obsessive disorder did not differ from those with schizophrenia alone with
      respect to measures of attention, executive functions and memory. Our findings do
      not support unique neuropsychological profile of schizo-obsessive disorder.
      Studying a larger sample of drug-naive patients in a longitudinal design may
      provide us more insights in to this.

PMID- 29061424
TI  - Dopamine transporter gene polymorphism in children with ADHD: A pilot study in
      Indonesian samples.
AB  - INTRODUCTION: Several studies showed that DAT1 polymorphism closed related with
      ADHD although the results were not consistently found. Studies in China, South
      Korea, Japan revealed that 10-repeat allele gave a risk for ADHD. Based on that
      understanding, this study tried to identify whether the similar polymorphism of
      DAT1 was also apparent in Indonesian children with ADHD. METHOD: This was a case 
      control study. Case was 50 Indonesian origin children with ADHD and without any
      other mental disorders and metal retardation. Control is Indonesian origin
      children without ADHD, other mental disorders and mental retardation. ADHD
      diagnosis was taken after doing the psychiatric interview and observation based
      on the DSM-IV TR diagnostic criteria for ADHD at the Child and Adolescent
      Psychiatry Out-patient Clinic, Dr. Cipto Mangunkusumo National Referral Hospital 
      Faculty of Medicine Universitas Indonesia. DNA isolation, DNA purity and
      concentration were measured. PCR was done by using a primer based on Homo sapiens
      solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3), RefSeq
      Gene on chromosome 5 with accession number NG_015885.1. To identify the serial of
      repeated allele, we used the sequencing technique. RESULTS: There were 47
      children with ADHD and 48 children without ADHD that involved in the final
      analysis. The mean of age amongst ADHD group was 9.18 (2.42) and 8.10 (2.46)
      years old in non-ADHD group. The 10-repeated allele of DAT1 was the highest
      proportion in both. CONCLUSION: This finding was apparently similar with other
      studies on DAT1 polymorphism across Asian.

PMID- 29061425
TI  - Valproic acid and alopecia: A two-edged sword.

PMID- 29061426
TI  - Anxiety symptoms mediate the relationship between exposure to stressful negative
      life events and depressive symptoms: A conditional process modelling of the
      protective effects of resilience.
AB  - BACKGROUND: Resilience has provided a useful framework that elucidates the
      effects of protective factors to overcome psychological adversities but studies
      that address the potential contingencies of resilience to protect against direct
      and indirect negative effects are lacking. These obvious gaps have also resulted
      in oversimplification of complex processes that can be clarified by moderated
      mediation associations. This study examines a conditional process modelling of
      the protective effects of resilience against indirect effects. METHOD: Two
      separate samples were recruited in a cross-sectional survey from Australia and
      Norway to complete the Patient Health Questionnaire -9, Generalized Anxiety
      Disorder, Stressful Negative Life Events Questionnaire and the Resilience Scale
      for Adults. The final sample sizes were 206 (females=114; males=91; other=1) and
      210 (females=155; males=55) for Australia and Norway respectively. Moderated
      mediation analyses were conducted across the samples. RESULTS: Anxiety symptoms
      mediated the relationship between exposure to stressful negative life events and
      depressive symptoms in both samples. Conditional indirect effects of exposure to
      stressful negative life events on depressive symptoms mediated by anxiety
      symptoms showed that high subgroup of resilience was associated with less effect
      of exposure to stressful negative life events through anxiety symptoms on
      depressive symptoms than the low subgroup of resilience. LIMITATIONS: As a cross
      sectional survey, the present study does not answer questions about causal
      processes despite the use of a conditional process modelling. CONCLUSIONS: These
      findings support that, resilience protective resources can protect against both
      direct and indirect - through other channels - psychological adversities.

PMID- 29061427
TI  - Population trends and public awareness of healthy and pathological ageing in
      India: A brief overview.
AB  - India is poised to experience dramatic shifts in the age and makeup of its
      population. Specifically, projections havehighlighted an increase in both the
      percentage of the elderly and those suffering from dementia-related
      disorders.Previous studies have examined the demographics of aging, its impact on
      the healthcare infrastructure and recommended policies to better cater to the
      elderly. This article focuses on a summary of these findings in relation to key
      stakeholders in the care of the elderly including mental health professionals,
      family caregivers, and public health officials. We broadly conclude that there
      exists a general shallow level of understanding of what constitutes pathological
      aging (i.e. dementia) across all stakeholders, and this creates a cascade of
      effects including delays in treatment seeking and barriers in conducting and
      having accurate demographic studies. Moreover, addressing this knowledge gap can
      help enhance communication between these three stakeholders in the hopes of the
      following: (a) increased education and awareness, (b) faster seeking of care, and
      (c) earlier diagnoses leading to better opportunities to collect accurate
      demographics of those suffering from dementia-related disorders.

PMID- 29061428
TI  - Psychometric properties of the AUDIT among men in Goa, India.
AB  - AIMS: The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item
      screening questionnaire used to detect alcohol use disorders. The AUDIT has been
      validated in only two studies in India and although it has been previously used
      in Goa, India, it has yet to be validated in that setting. In this paper, we aim
      to report data on the validity of the AUDIT for the screening of AUDs among men
      in Goa, India. METHODS: Concurrent and convergent validity of the AUDIT were
      assessed against the Mini International Neuropsychiatric Interview (MINI) and
      World Health Organisation Disability Assessment Scale (WHODAS) for alcohol abuse,
      alcohol dependence, and functional status respectively through the secondary
      analysis of data from a community cohort of men from Goa, India. RESULTS: The
      AUDIT showed high internal reliability and acceptable criterion validity with
      adequate psychometric properties for the detection of alcohol abuse and
      dependence. However, all of the optimal cut-off points from ROC analyses were
      lower than the WHO recommended for identification of risk of all AUDs, with a
      score of 6-12 detecting alcohol abuse and 13 and higher alcohol dependence.
      CONCLUSIONS: In order to optimize the utility of the AUDIT, a lowered cut-off
      point for alcohol abuse and dependence is recommended for Goa, India. Further
      validation studies for the AUDIT should be conducted for continued validation of
      the tool in other parts of India.

PMID- 29061430
TI  - Treatment of maternal depression in urban slums of Karachi, Pakistan: A
      randomized controlled trial (RCT) of an integrated maternal psychological and
      early child development intervention.
AB  - BACKGROUND: Maternal depression is a major public health problem. This may affect
      a mother's ability to provide adequate care for the child. The objective of this
      study was to evaluate the effectiveness of the Learning through Play Plus program
      (LTP Plus) - a parenting program integrated with Cognitive Behaviour Therapy
      (CBT). METHODS: A total of 247 women with symptoms of depression in Karachi,
      Pakistan were assigned randomly to either LTP Plus or routine care (Clinical
      Trials Identifier: NCT00835016). Symptoms of maternal depression were measured
      using the Edinburgh Postnatal Depression Scale (EPDS) at 3 and 6 months after
      baseline. RESULTS: At 3 months, there was a significant reduction in the EPDS
      scores in the intervention group compared to the routine group (adjusted mean
      difference [AMD] -3.65, 95% CI -6.14 to -1.15, p <0.004). This effect was
      sustained at 6 months (AMD -2.62, 95% CI -4.43 to -0.81, p<0.005). These women
      also reported less parental distress and disability. There was also a significant
      improvement in maternal knowledge about child development at 6 months.
      CONCLUSION: There was a significant reduction in depression among women who
      received the group parenting program LTP Plus. This intervention has the
      potential to be scaled up and integrated with mother and child health programs.

PMID- 29061429
TI  - Role of inflammatory and hemostatic biomarkers in Alzheimer's and vascular
      dementia - A pilot study from a tertiary center in Northern India.
AB  - INTRODUCTION: A reliable plasma biomarker in differentiating between Alzheimer's
      disease (AD) and Vascular dementia (VaD) is the need of the hour, in most memory
      clinics. Even though there is no disease modifying treatment, it is important to
      know the type of dementia for both symptomatic treatment and prognostication.
      METHODS: Neuropsychological assessment, MRI brain, FDG-PET brain and CSF
      biomarkers of AD (Abeta42 and total tau) were used for establishing the diagnosis
      of Mild Cognitive Impairment (MCI), AD or VaD. RESULTS: 68 diagnosed patients of
      AD/MCI/VaD were included. FDG PET brain, plasma fibrinogen, d dimer, IL6 and CRP
      were done in all 68 patients while 48 patients underwent CSF biomarker analysis.
      Sixteen patients had MCI, of which 11 were MCI-AD and 5 were MCI-VaSC. There were
      41 patients with AD (Mild AD-9, Mod AD-23, Severe AD-9) and 11 patients with VaD.
      Alzheimer group (MCI-AD and AD) and Vascular group (MCI VaSC & VaD) consisted of
      52 and 16 patients respectively. Alzheimer and Vascular groups did not exhibit
      significant difference in IL6 and CRP levels. Plasma fibrinogen levels were
      significantly higher in VaD and vascular group as compared to Alzheimer group.
      But MCI-VaSC was not significantly different from MCI-AD. Plasma d dimer levels
      were significantly higher in all vascular subgroups compared to Alzheimer
      subgroups except between MCI-VaSC and MCI-AD. CONCLUSION: Hemostatic biomarkers
      were higher in Vascular group compared to Alzheimer group whereas there was no
      difference in inflammatory biomarkers. But the sensitivity and specificity of
      fibrinogen and d-dimer were not high enough for routine clinical use. Further
      studies in a larger sample are required to confirm these results.

PMID- 29061431
TI  - Benefits associated with switching from benzodiazepine hypnotics to suvorexant in
      patients with mild primary insomnia.

PMID- 29061432
TI  - Effectiveness of a structured teaching program (STP) on cessation of tobacco
      chewing, on knowledge and attitude among female hospital housekeeping personnel -
      a pilot study.
AB  - AIM: To evaluate the effectiveness of a structured teaching program (STP) on: a)
      improving knowledge of female hospital housekeeping personnel regarding harmful
      impact of tobacco chewing and how to quit, and b) fostering an unfavorable
      attitude toward tobacco chewing. METHODS: The STP focused on adverse health
      effects of tobacco chewing, myths and facts, and tobacco cessation. It was
      administered in regional language to female hospital housekeeping personnel
      (N=35) over three days. Post-assessments were conducted at 4 weeks following the
      last session of the STP. RESULTS: Current tobacco use was reported by 26% of the
      sample. Tobacco chewers (vs. non-chewers) were more likely to be significantly
      older, have elementary education, belong to nuclear family, have lesser knowledge
      regarding harmful effects, and have a more favorable attitude toward the practice
      of tobacco chewing. At the end of 4 weeks following the STP, participants
      significantly improved their knowledge regarding the harmful health impact of
      tobacco chewing and how to quit (p=0.001), and showed a significantly less
      favorable attitude toward tobacco chewing (p=0.001). Change in participants'
      knowledge scores was found to be negatively correlated with change in attitude
      scores, implying that increase in knowledge was associated with less favorable
      attitude toward tobacco chewing (r=-0.427, p=0.011). CONCLUSION: Findings provide
      preliminary evidence for the effectiveness of health education on harmful impact
      of tobacco chewing and how to quit, delivered through a STP, in improving
      knowledge and fostering an unfavorable attitude toward tobacco chewing, among
      female hospital housekeeping personnel.

PMID- 29061433
TI  - Psychological recovery and its correlates in adults seeking outpatient
      psychiatric services: An exploratory study from an Indian tertiary care setting.
AB  - The study was designed to explore psychological recovery and its correlates in
      adults receiving outpatient mental health services for psychiatric disorders. It
      specifically aimed at examining the association of psychological recovery with
      symptomatic and functional recovery and with selected illness and treatment
      variables. The relationship of psychological recovery with perceived social
      support was also the focus of inquiry. The study utilized a cross sectional
      survey design with a sample of 90 participants diagnosed with severe and common
      mental illness who had been seeking outpatient psychiatric follow up services.
      The data was collected with the help of both clinician rated and self-rated
      measures. The study findings suggested that symptomatic, functional and
      psychological recovery are significantly correlated but not completely
      overlapping constructs. Nearly 40% of the sampled participants were at the lower
      stages of psychological recovery, despite the fact that a majority of them were
      rated by clinicians as having mild or lower severity of symptoms. With respect to
      socio-demographic variables, a significant association was found between higher
      levels of education and psychological recovery. The participants with common
      mental illness were significantly lower on self-reported improvement and higher
      on moratorium subscale of psychological recovery (as compared to those with
      severe mental illness), indicating their struggle in dealing with a sense of loss
      and despair. Findings also suggested that higher levels of overall perceived
      social support is likely to facilitate psychological recovery.

PMID- 29061434
TI  - Effect of relocation after a natural disaster in Armenia: 20-year follow-up.
AB  - BACKGROUND: This study is a 20-year follow-up of individual's relocated from
      their home after the devastating earthquake in Armenia in 1988. METHODS: Ninety
      seven subjects who were exposed to the earthquake and thirty-seven subjects who
      were not exposed to the earthquake were administered the Symptom Checklist-90-R
      (SCL 90) and the UCLA PTSD Reaction in 2008. The exposed subjects comprised three
      groups: subjects who stayed in the earthquake city; those who relocated and
      returned; and a group who left permanently but were visiting family at the time
      of the study. RESULTS: The Stayed group had significantly higher scores on the
      SCL-90-R when compared to the other three groups. The Stayed group and the
      Relocated group had significantly higher scores for partial and full PTSD than
      the Left group and the comparison group. CONCLUSION: Permanent relocation to
      another country where one is able to start a new life in a safe environment
      provides the best adaptation for recovery when the destruction and delay in
      reconstruction lasted as long as it did in Armenia.

PMID- 29061435
TI  - Pheochromocytoma presenting as anxiety disorder: A case report.

PMID- 29061436
TI  - Pattern and prevalence of psychiatric disorders among patients attending
      dermatology OPD.
AB  - BACKGROUND: Consideration of psychiatric and psychosocial factors is important
      for the management and prevention of dermatologic disorders. Dermatology patients
      suffer commonly from psychiatric comorbidity. AIM: To study pattern and
      prevalence of psychiatric disorders among patient attending dermatology OPD.
      METHODS: The study was carried out in Psychiatry department of NIMS Medical
      College, Jaipur, Rajasthan, a north State of India. The sample was taken from
      Dermatology department of Medical College. All the participants were
      diagnosed/confirmed cases of skin diseases. Socio-demographic data was collected.
      Patients scoring more than 12 on GHQ were examined for presence of psychiatric
      illness. Clinical interview & Mental Status Examination (MSE) of these patients
      was carried out to ascertain diagnosis according to ICD-10. FINDINGS: As per ICD
      10 diagnosis 34.2% of total sample were diagnosed with definite Psychiatric
      comorbidity. Maximum number of cases were of Depression 36.32% (N=146) followed
      by Anxiety disorder 18.41% (74) and 7.96% (N=32) with Somatoform disorder.
      Obsessive compulsive disorder was diagnosed in 6.47% (N=26) followed by
      Adjustment disorder 4.98% (N=20) and Alcohol dependence syndrome 4.98% (N=20).
      Minimum number of cases belonged to Schizophrenia 2.99% (N=12) and Bipolar
      Affective Disorder 2.99% (N=12). No diagnosis was found in 14.93% (N=60).
      CONCLUSION: Significant psychiatric comorbidity exists in patients of
      dermatology. Biopsychosocial approach to patients with skin disease should be
      sought by liaison between psychiatrist and dermatologist.

PMID- 29061437
TI  - Obsession of pregnancy: Does it exist?

PMID- 29061438
TI  - Symptom profile of catatonia in children and adolescents admitted to psychiatry
      inpatient unit.
AB  - AIM: To study the symptom profile of catatonia in children and adolescents.
      METHODOLOGY: Treatment records of all the inpatients aged (<=19 years) were
      reviewed for the period January 2005 to January 2017. Patients with catatonia
      (diagnosed as having at least two symptoms as per the Bush Francis Catatonia
      Rating scale) were included. RESULTS: During the study period, data was available
      for 52 children and adolescent. The mean age of the sample was 16.8 years
      (SD=2.0; range 9-19). Males (N=28; 53.8%) outnumbered females. The most common
      primary psychiatric diagnostic category was that of psychotic disorders (N=26;
      78.8%). One-sixth (N=8; 15.4%) were diagnosed with organic illnesses like
      epilepsy and systemic lupus erythematosus. Affective disorders accounted for only
      one-tenth (N=5; 9.6%) of cases, with mania being more common presentation than
      depression. Very few patients were diagnosed with pervasive developmental
      disorder (N=2). The common signs and symptoms noted were mutism (90.4%) followed
      by immobility/stupor (75%), staring (71.2%), negativism (57.7%), rigidity (55.8%)
      and posturing (53.8%). The mean BFCRS score was 13.73 (SD - 7.6; range 3-20).
      Overall there was no significant difference in the prevalence of various signs
      and symptoms of catatonia between those with psychotic disorders, affective
      disorders and those with catatonia due to organic causes. In only half of the
      patients catatonia responded to lorazepam and other half required
      electroconvulsive therapy. CONCLUSION: The most common symptoms of catatonia in
      children and adolescent are mutism, immobility/stupor, staring, posturing,
      negativism and rigidity. The most common underlying psychiatric diagnosis is that
      of schizophrenia.

PMID- 29061439
TI  - Incremental validity of the Child Behavior Checklist (CBCL) and the Strengths and
      Difficulties Questionnaire (SDQ) in Vietnam.
AB  - OBJECTIVE: Valid but efficient psychiatric assessment is essential for mental
      health development in Asian low and middle-income countries. This study's
      objective was to assess the validity of Vietnamese versions of the Child Behavior
      Checklist (CBCL), and the Strengths and Difficulties Questionnaire (SDQ) in
      Vietnam. METHODS: Measures were completed by a community sample of 1314 parents
      of children 6-16 years old from 10 Vietnamese provinces, and by parents of 208
      children recruited from 3 psychiatric facilities in Hanoi. RESULTS: Internal
      consistency was in the fair to excellent range for all CBCL scales (.76-.96) and
      for the SDQ Total Problems scale (.81); SDQ subscale internal consistency was in
      the poor to fair range (.31-.73). All CBCL and SDQ scales and most individual
      items significantly discriminated between referred and non-referred children,
      with referred children scoring in the more pathological direction; the CBCL had
      significantly larger referral effect sizes than the SDQ for all four pairs of
      comparable scales. At the item level, the largest referral status effect for the
      CBCL were #73 (Sexual Problems), #84 (Strange Behavior), and #91 (Talks about
      suicide), and for the SDQ they were #10 (Constantly fidgeting), #15 (Easily
      Distracted) and # 25 (Good Attention Span-reverse scored). Five CBCL (#2 Drinks
      alcohol; #99 Uses tobacco, #32 Has to be perfect; #53 Overeats; #56A Aches and
      pains) and one SDQ items (#23 Gets along better with adults than children) did
      not discriminate referral status, suggesting the influence of cultural values on
      clinical referrability (e.g., that Vietnamese parents may not see use of tobacco
      as an issue of concern, or related to health). CONCLUSIONS: There is good support
      for the reliability and validity of the Vietnamese version of the CBCL, and for
      the SDQ Total Problems scale. Overall, the CBCL appears to be the stronger
      measure psychometrically, particularly if in-depth assessment is needed.

PMID- 29061440
TI  - Pipkin Type-III fractures of the femoral head: Fix it or replace it?

PMID- 29061441
TI  - Cardiac oxidative stress following maternal separation stress was mitigated
      following adolescent voluntary exercise in adult male rat.
AB  - Early life stress (ELS) is known as a risk factor for the development of
      depression and its associated comorbidities, such as cardiomyopathy in depressed
      patients. Mitochondrial dysfunction plays a critical role in the pathophysiology
      of depression and cardiovascular diseases. Evidence indicates that regular
      physical activity has therapeutic effects on both mood and cardiovascular
      disorders. Therefore, the voluntary running wheel exercise (RW) during
      adolescence may be able to attenuate the negative impact of maternal separation
      stress (MS) as a valid animal model of depression on the behavior and cardiac
      mitochondrial function of adult rats. To do this, we applied MS to rat pups by
      separating them from their mothers for 180min during the postnatal day (PND) 2 to
      PND 14. Next, the animals were randomly divided into different treatment groups
      (fluoxetine [FLX] and RW) and received the treatments during adolescence, between
      PND 28 to PND 60. Then, we evaluated the effects of MS on the rat behaviors test,
      and finally, we assessed reactive oxygen species, mitochondrial glutathione, ATP
      and cytochrome c release in the cardiac tissue of animals. Our results showed
      that depressive-like behaviors following MS in adult male rats were associated
      with oxidative stress in cardiac tissue. Further, we found that treating animals
      with chronic FLX or RW during adolescence improved animal's behavior as well as
      cardiac mitochondrial function. The results of this study highlight the
      importance of adolescence as a period during which treating animals with non
      pharmacological agents has significant protective effects against the negative
      influence of ELS on mood and cardiac energy hemostasis.

PMID- 29061442
TI  - A novel glycoprotein D-specific monoclonal antibody neutralizes herpes simplex
      virus.
AB  - The worldwide prevalence of herpes simplex virus (HSV) and the shortage of
      efficient vaccines and novel therapeutic strategies against HSV are widely global
      concerns. The abundance on the virion and the major stimulus for the virus
      neutralizing antibodies makes gD a predominant candidate for cure of HSV
      infection. In this study, we generated a monoclonal antibody (mAb), termed m27f,
      targeting to glycoprotein D (gD) of HSV-2, which also has cross-reactivity
      against HSV-1 gD. It has a high level of neutralizing activity against both HSV-1
      and HSV-2, and binds to a highly conserved region (residues 292-297) within the
      pro-fusion domain of gD. It can effectively block HSV cell-to-cell spread in
      vitro. The pre- or post-attachment neutralization assay and syncytium formation
      inhibition assay revealed that m27f neutralizes HSV at the post-binding stage.
      Moreover, therapeutic administration of m27f completely prevented infection
      related mortality of mice challenged with a lethal dose of HSV-2. Our newly
      identified epitope for the neutralizing antibody would facilitate studies of gD
      based HSV entry or vaccine design, and m27f itself demonstrated a high potential
      for adaptation as a protective or therapeutic drug against HSV.

PMID- 29061443
TI  - Outcomes of lupus and rheumatoid arthritis patients with primary dengue
      infection: A seven-year report from Brazil.
AB  - OBJECTIVE: We described the clinical profile and outcomes of patients with SLE
      and RA diseases reported to the Brazilian Health Information System with primary
      dengue infection. METHODS: Databases from the Brazilian Public Health Informatics
      System (SUS) were linked as the source of information. Three databases comprising
      different longitudinal information of lupus or rheumatoid arthritis (RA) patients
      under treatment and care through the Brazilian Health System were linked.
      Patients who had lupus ICD-9 code or RA ICD-9 code and their treatment approved
      by SUS were included in the study. In Study 1, we described the clinical
      characteristics of RA/lupus patients who had dengue infection. In Study 2, we
      compared RA/lupus patients with or without dengue for hospitalization rates after
      index dengue diagnosis for dengue-exposed or matching date for dengue-unexposed.
      RESULTS: We included 69 SLE and 301 RA patients with dengue. In the RA/lupus with
      dengue case series, hospitalization was found in 24.6% of lupus subjects and of
      11.2% of RA subjects. It differed by geographic region (p = 0.03), gender (p =
      0.05) and the use of azathioprine (p = 0.02). Dengue was the most frequent reason
      for hospitalization reported (43.0%). Hospitalization due to dengue was noted in
      12 (42.9%) dengue-exposed patients (p = 0.02), while rheumatoid arthritis was
      reported as the cause of hospitalization in 22.2% of dengue-unexposed (p =
      0.005). Five deaths were reported among the dengue-exposed and none among dengue
      unexposed. Bacterial infection was the most frequent cause of death. We found
      that the dengue exposure was associated with an increased risk of hospitalization
      outcome in RA and lupus patients (RR = 6.2; 95% CI: 2.99-12.94). SUMMARY: We
      found that when comparing RA/lupus patients with or without dengue, dengue
      exposed patients had an increased rates of hospitalization and death.

PMID- 29061444
TI  - It's all relative: The role of object weight in toddlers' gravity bias.
AB  - Work over the past 20 years has demonstrated a gravity bias in toddlers; when an
      object is dropped into a curved tube, they will frequently search at a point
      immediately beneath the entry of the tube rather than in the object's actual
      location. The current study tested 2- to 31/2-year-olds' (N = 88) gravity bias
      under consideration of object weight. They were tested with either a heavy or
      light ball, and they had information about either one of the balls only or both
      balls. Evaluating their first search behavior showed that participants generally
      displayed the same age trends as other studies had demonstrated, with older
      toddlers passing more advanced task levels by being able to locate objects in the
      correct location. Object weight appeared to have no particular impact on the
      direction of these trends. However, where weight was accessible as relative
      information, toddlers were younger at passing levels and older at failing levels,
      although significantly so only from around 3 years of age onward. When they
      failed levels, toddlers made significantly more gravity errors with the heavy
      ball when they had information about both balls and made more correct choices
      with the light ball. As a whole, the findings suggest that nonvisual object
      variables, such as weight, affect young children's search behaviors in the
      gravity task, but only if these variables are presented in relation to other
      objects. This relational information has the potential to enhance or diminish the
      gravity bias.

PMID- 29061445
TI  - Amelioration of NK cell function driven by Valpha24+ invariant NKT cell
      activation in multiple myeloma.
AB  - NK cells represent a first line of immune defense, but are progressively
      dysregulated in multiple myeloma (MM) patients. To restore and facilitate their
      antitumor effect, NK cells are required in sufficient quantities and must be
      stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM
      patients. The frequencies of both in PBMC populations correlated with those in
      BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect
      of stimulating NKT cells with CD1d and alpha-GalCer complexes on the NK cells.
      The expression of NKG2D on CD56dimCD16+ NK cells and DNAM-1 on CD56brightCD16- NK
      cells increased after NKT cell activation. Apparently, NK cell-mediated anti
      tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus,
      NK cell function in patients could be ameliorated, beyond the effect of
      immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could
      represent a potential new treatment modality.

PMID- 29061446
TI  - Increased proportion of a CD38highIgD+ B cell subset in peripheral blood is
      associated with clinical and immunological features in patients with primary
      Sjogren's syndrome.
AB  - We investigated the correlation between the increased proportion of peripheral B
      cell subsets and clinical and immunological features in primary Sjogren's
      syndrome (pSS). We found that the proportion of CD19+ B cells was significantly
      increased in pSS as compared with HC and was correlated with serum IgG levels.
      Moreover, in vitro IgG production by CD19+ B cells was significantly increased in
      pSS and was positively and significantly correlated with serum IgG levels. FACS
      analysis revealed that the proportions of peripherally CD38highIgD+ B cells and
      CD38highIgD- B cells were significantly increased in pSS. In addition, the
      proportion of CD38highIgD+ B cells positively correlated with ESSDAI scores and
      serum levels of IgG, anti-Ro/SSA and anti-La/SSB antibodies while that of
      CD38highIgD- B cells showed no correlation with these parameters. Our data
      suggest that increased proportion of CD38highIgD+ B cells in pSS is involved in
      IgG overproduction including autoantibodies, and correlates with disease
      progression.

PMID- 29061447
TI  - PDK1 promotes apoptosis of chondrocytes via modulating MAPK pathway in
      osteoarthritis.
AB  - 3-Phosphoinositide dependent protein kinase-1 (PDK1), a serine threonine kinase,
      belongs to the AGC kinase family and is associated with apoptosis. The aim of
      this study was to investigate the expression of PDK1 (3-Phosphoinositide
      dependent protein kinase-1) in articular cartilage with osteoarthritis (OA) and
      to analyze the relationship between PDK1 and chondrocyte apoptosis.
      Immunohistochemistry and RT-PCR analysis showed that the expression of PDK1 in
      articular cartilage of OA patients and healthy controls. IL-1beta-stimulated
      SW1353 cells were used to imitate the OA-like chondrocyte injury in vitro, and IL
      1beta-induced the expression of PDK1, apoptotic markers(PARP, caspase-3), and
      phosphorylated p38 were detected by Western blot. The co-localization of PDK1 and
      Cleaved-caspase3 was confirmed through immunofluorescence. Knocking down PDK1
      expression through PDK1 siRNA. Western blot was performed to detect the knockdown
      efficiency of PDK1 and the impact of PDK1 knockout on IL-1beta-induced expression
      of apoptotic markers and phosphorylated p38 in SW1353 cells. Flow Cytometry-Based
      Annexin V/PI Staining was used to exam chondrocyte apoptosis. Our experimental
      results suggested that PDK1 may promote chondrocyte apoptosis in OA via p38 MAPK
      signaling pathway.

PMID- 29061448
TI  - Scorpions pectines - Idiosyncratic chemo- and mechanosensory organs.
AB  - Scorpions possess specialised chemosensory appendages, the pectines. These comb
      shaped limbs are located ventrally behind the walking legs. Like the antennae of
      mandibulate arthropods, they also serve a mechanosensory function. However, more
      than 90% of the sometimes well above 100,000 sensory neurons projecting from a
      pectine to the central nervous system are chemosensory. There are two primary
      projection neuropils. The posterior one, immediately adjacent to the pectine
      nerve entrance, has an intriguing substructure reminiscent of the olfactory
      glomeruli observed in the primary chemosensory neuropils of many arthropods and
      indeed of most bilaterian animals. There are further similarities, particularly
      to the antennal lobes of mandibulate arthropods, including dense innervation by a
      relatively small number of putative serotonergic interneurons and the presence of
      GABA immunoreactivity, indicative of inhibitory interactions. Scorpion
      idiosyncrasies include the flattened shape and broad size range of the glomerulus
      like neuropil compartments. Further, these compartments are often not clearly
      delimited and form layers in the neuropil that are arranged like onion peels. In
      summary, the pectine appendages of scorpions and their central nervous
      projections appear as promising study subjects, particularly regarding
      comparative examination of chemosensory representation and processing strategies.
      The possibility of combined, rather than discrete, representations of chemo- and
      mechanosensory inputs should merit further study.

PMID- 29061449
TI  - Influence of Lumbar Lordosis on the Outcome of Decompression Surgery for Lumbar
      Canal Stenosis.
AB  - OBJECTIVE: Although sagittal spinal balance plays an important role in spinal
      deformity surgery, its role in decompression surgery for lumbar canal stenosis is
      not well understood. To investigate the hypothesis that sagittal spinal balance
      also plays a role in decompression surgery for lumbar canal stenosis, a
      prospective cohort study analyzing the correlation between preoperative lumbar
      lordosis and outcome was performed. METHODS: A cohort of 85 consecutive patients
      who underwent decompression for lumbar canal stenosis during the period 2007-2011
      was analyzed. Standing lumbar x-rays and 36-item short form health survey
      questionnaires were obtained before and up to 2 years after surgery. Correlations
      between lumbar lordosis and 2 parameters of the 36-item short form health survey
      (average physical score and bodily pain score) were statistically analyzed using
      linear mixed effects models. RESULTS: There was a significant correlation between
      preoperative lumbar lordosis and the 2 outcome parameters at postoperative, 6
      month, 1-year, and 2-year time points. A 10 degrees  increase of lumbar lordosis
      was associated with a 5-point improvement in average physical scores. This
      correlation was not present in preoperative scores. CONCLUSIONS: This study
      showed that preoperative lumbar lordosis significantly influences the outcome of
      decompression surgery on lumbar canal stenosis.

PMID- 29061450
TI  - The History of Neurosurgery in the Hawaiian Islands.
AB  - The field of neurosurgery has a rich and fascinating history. The development of
      the specialty in Hawaii has been particularly unique, given the state's remote
      location, indigenous population, and military presence. The life of Dr. Ralph B.
      Cloward, Hawaii's most noted neurosurgeon, has received some attention in the
      literature. However, a comprehensive review of this history, including the pre
      Cloward and post-Cloward era, is lacking. This article will review and chronicle
      the development of neurosurgery in Hawaii with special attention to 3 topics: the
      traveling neurosurgeons of the early 20th century, such as Dr. Frederick
      Reichert; Hawaii's first full time neurosurgeon, Dr. Cloward; and finally, the
      current state of neurosurgery in Hawaii.

PMID- 29061451
TI  - Training Neurosurgery and Radiation Oncology Residents in Stereotactic
      Radiosurgery: Assessment Gathered from Participants in AANS and ASTRO Training
      Course.
AB  - OBJECTIVE: Stereotactic radiosurgery (SRS) represents an expanding approach for
      neurosurgeons and radiation oncologists. We evaluate educational gaps of senior
      residents drawn from each specialty as part of a focused SRS course. We also
      evaluate the strengths and limitations of SRS training in current residency
      programs of the course residents and faculty. METHODS: The American Association
      of Neurological Surgeons and American Society of Radiation Oncology jointly held
      a senior resident course in SRS. Residents were nominated by program directors
      from across the United States. Thirty residents were chosen to participate in the
      course. The residents were surveyed before and after the course. Faculty (n = 14)
      were also surveyed to ascertain their perspectives on current training in SRS.
      RESULTS: Most (96.7%) of the residents planned to perform SRS when finished, and
      94% anticipated SRS indications to expand. Regarding SRS technique, 47% reported
      average/above average understanding of intracranial SRS; only 17% expressed
      similar understanding of spinal SRS. Before the course, 76.6% noted below
      average/average ability to recognize and manage SRS complications. Twenty-three
      percent of the faculty indicated that graduating residents from their programs
      were unprepared to perform radiosurgery. Residents' self-assessed understanding
      of brain SRS indication (P = 0.000693), SRS techniques (P = 0.000021), spinal SRS
      indications (P = 0.000050), spinal SRS techniques (P = 0.000019), and
      complication recognition and management (P = 0.00033) significantly improved
      following the course. CONCLUSIONS: Knowledge and training gaps in SRS appear
      evident to the senior residents and faculty of both specialties. We believe that
      other educational opportunities for SRS experience are necessary to optimize
      clinical competency, as well as meet future clinical staffing needs for this
      expanding, multidisciplinary approach. Further evaluation of gaps in SRS is
      necessary through a larger, nationwide survey of U.S. neurosurgeons, program
      directors, and residents.

PMID- 29061452
TI  - A Submammarian Approach for Cosmetically Improved Implantation of Deep Brain
      Stimulation Generators.
AB  - BACKGROUND: Deep brain stimulation (DBS) indications include movement disorders,
      psychiatric affections, or epilepsy in which patients risk social isolation
      heightened by abnormal motions or behavioral patterns. Further stigmatization
      after DBS surgery from head shaving, visible scarring, or disfigurement from
      bulky lead insertion points should be avoided. OBJECTIVE: We present a
      cosmetically optimized, adapted submammarian approach for DBS neurostimulator
      implantation that leaves the decolletage untouched. METHODS: Over 24 months, 61
      patients suffering from Parkinson disease, dystonia, or tremor underwent DBS
      surgery. The modified, submammarian approach was compared with the conventional
      infraclavicular approach regarding clinical outcome, complications, and
      limitations over a 5-year follow-up. RESULTS: Neurostimulators were implanted in
      a paraumbilical (n = 20) or infraclavicular position (n = 41; Parkinson disease,
      n = 27; dystonia, n = 9; tremor, n = 5), the latter using a standard (n = 16),
      modified juxta-axillary (n = 6), or submammarian approach (n = 19; 18 women, 1
      man with significant gynecomastia). After 12 months, there was no significant
      difference in the infection rate and one event of rebleeding in each group.
      Overall, operation time was longer (+20 minutes) for the submammarian versus
      standard, infraclavicular approach, but acceptable. Neurostimulator replacement
      was, necessary within 5 years due to advanced battery discharge (n = 32). Battery
      replacement was easily achieved using the submammarian approach (n = 14), again
      with increased surgical time (+20 minutes), and iatrogenic damage to extensions
      was avoidable. CONCLUSIONS: A submammarian approach might be an alternative for
      infraclavicular implantation of DBS neurostimulators, particularly in female
      patients in the context of cosmetically optimized surgery. Patients' self
      perception and self-esteem may be strengthened, potentially enabling them to
      better cope with disease.

PMID- 29061453
TI  - Prevention of the Rerupture of Collateral Artery Aneurysms on the Ventricular
      Wall by Early Surgical Revascularization in Moyamoya Disease: Report of Two Cases
      and Review of the Literature.
AB  - BACKGROUND: Collateral artery aneurysms are a source of intracranial hemorrhage
      in moyamoya disease. Several reports have shown that surgical revascularization
      leads to the obliteration of collateral artery aneurysms. However, its effect on
      the prevention of rebleeding has not been established, and the optimal timing of
      the operation remains unclear. The purpose of the present study is to evaluate
      the effects of surgical revascularization and to investigate the optimal
      operation timing in patients with moyamoya disease who have ruptured collateral
      artery aneurysms on the ventricular wall. CASE DESCRIPTION: Two patients with
      moyamoya disease who presented with intraventricular hemorrhage caused by rupture
      of collateral artery aneurysms on the wall of the lateral ventricle are presented
      here. In both cases, the aneurysms reruptured approximately 1 month after the
      initial hemorrhage. Both patients successfully underwent superficial temporal
      artery-middle cerebral artery anastomosis combined with indirect bypass in the
      subacute stage. The aneurysms decreased with the development of collateral
      circulation through the direct bypasses, and rebleeding did not occur after the
      surgery. CONCLUSIONS: Because ruptured collateral artery aneurysms on the wall of
      the lateral ventricle in moyamoya disease are prone to rerupture within 1 month,
      surgical revascularization may be recommended as soon as the patients are stable
      and able to withstand the operation.

PMID- 29061454
TI  - Malignant Peripheral Nerve Sheath Tumor in a Patient With BAP1 Tumor
      Predisposition Syndrome.
AB  - BACKGROUND: Germline pathogenic variants in BRCA1-associated protein-1 (BAP1), a
      nuclear ubiquitin carboxy-terminal hydrolase with evidence suggestive of
      independent tumor suppressor function, predispose affected families to uveal
      melanoma, cutaneous melanoma, renal cell carcinoma, malignant mesothelioma, and
      possibly a range of other tumors and malignancies as part of the BAP1 tumor
      predisposition syndrome, a recently recognized hereditary cancer syndrome. CASE
      DESCRIPTION: A 50-year-old woman presented with a malignant peripheral nerve
      sheath tumor of the left fifth metatarsal head. Further examination revealed a
      right renal mass and left breast mass. Her family history was significant for
      astrocytoma, melanoma, cholangiocarcinoma, hepatocellular carcinoma, renal cell
      carcinoma, prostate cancer, non-Hodgkin lymphoma, and pancreatic adenocarcinoma.
      Genetic testing revealed a BAP1 mutation in the proband. CONCLUSIONS: Although
      there have been reports of sarcomas and meningiomas in patients affected with
      BAP1 mutations, to our knowledge malignant peripheral nerve sheath tumors in this
      patient population have not been previously reported. We report a case of
      malignant peripheral nerve sheath tumor in a patient affected by a BAP1 mutation.

PMID- 29061456
TI  - Multilayer Dura Reconstruction After Thoracoscopic Microdiscectomy: Technique and
      Results.
AB  - BACKGROUND: Anterior transthoracic approaches, including thoracoscopic
      microdiscectomy (TMD), are the preferred techniques for central, broad-based,
      calcified thoracic disc herniations (TDHs). Dural defects due to manipulation or
      transdural extension may create a potentially life-threatening subarachnoid
      pleural fistula. We evaluate a fast, sutureless technique for reconstructing the
      dura. METHODS: We analyzed 476 anterior transthoracic approaches for TDHs (437
      TMDs, 31 mini-thoracotomies, 7 transaxillary approaches, and 1 sternotomy). Dural
      defects were closed using an onlay dura substitute, fibrin glue, an autologous
      fat graft, and another layer of fibrin glue topped by an absorbable gelatin
      sponge. A chest tube was used to provide a water seal, and the use of external
      lumbar drains (ELDs) was discontinued in recent years. RESULTS: We encountered 35
      dural defects (7.35%), including 27 in 279 procedures (9.67%) in the first 10
      years and 8 in 197 (4.06%) in the past 6 years. Five defects were large, 23 were
      relatively small, and 5 had an intact arachnoid layer, likely preventing
      cerebrospinal fluid (CSF) egress. Two CSF leaks in the early series were
      overlooked intraoperatively; 1 patient died following widespread cortical venous
      thrombosis, whereas the other merely had a headache that disappeared within 1
      week. Overall, an ELD was inserted in 3 of 5 large defects and in 17 of 23 small
      defects; however, in the past 6 years, an ELD was inserted in no large defects
      and in only 1 of 5 small defects. The technique was successful in all but 1
      patient, who underwent reoperation using a larger fat graft. CONCLUSIONS: Dural
      defects encountered during anterior transthoracic approaches to TDHs can be
      reconstructed endoscopically, while avoiding the use of an ELD in most cases.

PMID- 29061455
TI  - Epidermal Growth Factor Receptor Expression Predicts Time and Patterns of
      Recurrence in Patients with Glioblastoma After Radiotherapy and Temozolomide.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the potential
      role of epidermal growth factor receptor (EGFR) protein expression in predicting
      the modality of treatment failure in glioblastoma (GB). METHODS: Patients with
      unifocal GB undergoing surgery and postoperative radiochemotherapy from February
      2008 to July 2015 were included into the study. The EGFR protein expression level
      was assessed by immunohistochemistry in GB tissues and classified into high and
      low expression. Time to progression (TTP) and pattern of recurrence (PR) were
      evaluated. PRs were classified as central, in-field, marginal, or distant
      recurrences. RESULTS: After a median follow-up time of 13 months (range, 6-67
      months), 102 patients (79.1%) showed recurrences that were detectable on magnetic
      resonance imaging. Median TTP was 9 months after the completion of
      radiochemotherapy. EGFR expression was significantly correlated with TTP (log
      rank test, P = 0.003) and PR (Fisher exact test, P = 0.01). The low-EGFR group
      had a median TTP of 13 months and a prevalence of central/in-field recurrences
      (accounting to a total 81%). The high-EGFR group had a shorter median TTP (6
      months) and a higher rate of marginal/distant recurrences (55.6%). CONCLUSIONS:
      Different modality of recurrence related to EGFR expression in patients with GB
      envisages implication for target contouring of radiotherapy volumes and other
      therapeutic strategies.

PMID- 29061458
TI  - Unilateral Symptomatic Hypertrophic Olivary Degeneration Secondary to Midline
      Brainstem Cavernous Angioma: A Case Report and Review of the Literature.
AB  - BACKGROUND: Hypertrophic olivary degeneration (HOD) is a rare phenomenon in the
      dento-rubro-olivary pathway caused by lesion or disruption of the fibers of the
      Guillain-Mollaret triangle. Hemorrhage of pontine and midbrain cavernous angiomas
      can rarely lead to HOD portending neurologic deterioration and possible
      concomitant life-threatening complications; for this reason, it may define a
      poignant consideration in planning intervention. CASE DESCRIPTION: The patient
      was a 57-year-old woman with known midbrain-pontine cavernous angioma. For
      several years, the lesion had been stable, as shown by imaging follow-up, until
      10 months before the patient presented with falls, dysarthria, and headache.
      Imaging showed some decrease in size as well as blood product around the
      cavernous angioma, suggesting interim period hemorrhage and interval development
      of HOD. CONCLUSIONS: The literature regarding imaging recommendations for stable
      cavernous angioma in the midbrain-pontine junction is reviewed. The implication
      of HOD for patient outcome is discussed and a comment is made on how the
      development of HOD may affect management of the cavernous angioma.

PMID- 29061457
TI  - 3D-Printed Craniosynostosis Model: New Simulation Surgical Tool.
AB  - BACKGROUND: Craniosynostosis is a complex disease once it involves deep anatomic
      perception, and a minor mistake during surgery can be fatal. The objective of
      this report is to present novel 3-dimensional-printed polyamide craniosynostosis
      models that can improve the understanding and treatment complex pathologies.
      METHODS: The software InVesalius was used for segmentation of the anatomy image
      (from 3 patients between 6 and 9 months old). Afterward, the file was transferred
      to a 3-dimensional printing system and, with the use of an infrared laser, slices
      of powder PA 2200 were consecutively added to build a polyamide model of cranial
      bone. RESULTS: The 3 craniosynostosis models allowed fronto-orbital advancement,
      Pi procedure, and posterior distraction in the operating room environment. All
      aspects of the craniofacial anatomy could be shown on the models, as well as the
      most common craniosynostosis pathologic variations (sphenoid wing elevation,
      shallow orbits, jugular foramen stenosis). Another advantage of our model is its
      low cost, about 100 U.S. dollars or even less when several models are produced.
      CONCLUSIONS: Simulation is becoming an essential part of medical education for
      surgical training and for improving surgical safety with adequate planning. This
      new polyamide craniosynostosis model allowed the surgeons to have realistic
      tactile feedback on manipulating a child's bone and permitted execution of the
      main procedures for anatomic correction. It is a low-cost model. Therefore our
      model is an excellent option for training purposes and is potentially a new
      important tool to improve the quality of the management of patients with
      craniosynostosis.

PMID- 29061459
TI  - Spaceflight and Neurosurgery: A Comprehensive Review of the Relevant Literature.
AB  - OBJECTIVE: Spaceflight and the associated gravitational fluctuations may impact
      various components of the central nervous system. These include changes in
      intracranial pressure, the spine, and neurocognitive performance. The
      implications of altered astronaut performance on critical spaceflight missions
      are potentially significant. The current body of research on this important topic
      is extremely limited, and a comprehensive review has not been published. Herein,
      the authors address this notable gap, as well as the role of the neurosurgeon in
      optimizing potential diagnostic and therapeutic modalities. METHODS: A literature
      search was conducted using the PubMed, EMBASE, and Google Scholar databases, with
      no time constraints. Significant manuscripts on physiologic changes associated
      with spaceflight and microgravity were identified and reviewed. Manifestations
      were separated into 1 of 3 general categories, including changes in intracranial
      pressure, the spine, and neurocognitive performance. RESULTS: A comprehensive
      literature review yielded 27 studies with direct relevance to the impact of
      microgravity and spaceflight on nervous system physiology. This included 7
      studies related to intracranial pressure fluctuations, 17 related to changes in
      the spinal column, and 3 related to neurocognitive change. CONCLUSIONS: The
      microgravity environment encountered during spaceflight impacts intracranial
      physiology. This includes changes in intracranial pressure, the spinal column,
      and neurocognitive performance. Herein, we present a systematic review of the
      published literature on this issue. Neurosurgeons should have a key role in the
      continued study of this important topic, contributing to both diagnostic and
      therapeutic understanding.

PMID- 29061460
TI  - Cervical Vertigo: Historical Reviews and Advances.
AB  - Vertigo is one of the most common presentations in adult patients. Among the
      various causes of vertigo, so-called cervical vertigo is still a controversial
      entity. Cervical vertigo was first thought to be due to abnormal input from
      cervical sympathetic nerves based on the work of Barre and Lieou in 1928. Later
      studies found that cerebral blood flow is not influenced by sympathetic
      stimulation. Ryan and Cope in 1955 proposed that abnormal sensory information
      from the damaged joint receptors of upper cervical regions may be related to
      pathologies of vertigo of cervical origin. Further studies found that cervical
      vertigo seems to originate from diseased cervical intervertebral discs. Recent
      research found that the ingrowth of a large number of Ruffini corpuscles into
      diseased cervical discs may be related to vertigo of cervical origin. Abnormal
      neck proprioceptive input integrated from the signals of Ruffini corpuscles in
      diseased cervical discs and muscle spindles in tense neck muscles secondary to
      neck pain is transmitted to the central nervous system and leads to a sensory
      mismatch with vestibular and other sensory information, resulting in a subjective
      feeling of vertigo and unsteadiness. Further studies are needed to illustrate the
      complex pathophysiologic mechanisms of cervical vertigo and to better understand
      and manage this perplexing entity.

PMID- 29061461
TI  - A Propensity Score Analysis of the Impact of Dexamethasone Use on Delayed
      Cerebral Ischemia and Poor Functional Outcomes After Subarachnoid Hemorrhage.
AB  - OBJECTIVE: An inflammatory response occurs after aneurysmal subarachnoid
      hemorrhage (aSAH) and predicts poor outcomes. Glucocorticoids suppress
      inflammation and promote fluid retention. Dexamethasone is often administered
      after aSAH for postoperative cerebral edema and refractory headache. Our
      objective was to examine the impact of dexamethasone use on functional outcomes
      and delayed cerebral ischemia (DCI) after aSAH. METHODS: Patients with aSAH
      admitted between 2010 and 2015 were included; the data source was a single-center
      subarachnoid hemorrhage registry. The intervention of interest was a
      dexamethasone taper used <7 days from ictus. The primary outcome was poor
      discharge functional outcome, with a modified Rankin Scale score >3. Other
      outcomes included DCI and infection. A propensity score for use of dexamethasone
      was calculated using a logistic regression model that included potential
      predictors of dexamethasone use and outcome. The impact of dexamethasone on
      outcomes of interest was calculated and the propensity score was controlled for.
      RESULTS: A total of 440 patients with subarachnoid hemorrhage were admitted
      during the study period and 309 met eligibility criteria. Dexamethasone was
      administered in 101 patients (33%). A total of 127 patients (41%) had a discharge
      modified Rankin Scale score >3, 105 (34%) developed DCI, and 94 (30%) developed
      an infection. After propensity score analysis, dexamethasone use was associated
      with a significant reduction in poor functional outcomes (odds ratio [OR], 0.35;
      95% confidence interval [CI], 0.19-0.66) but showed no significant association
      with DCI (OR, 0.93; 95% CI, 0.53-1.64) or infection (OR, 0.60; 95% CI, 0.34
      1.06). CONCLUSIONS: Dexamethasone use after aSAH was associated with a reduction
      in poor functional outcomes at discharge but not DCI, controlling for predictors
      of dexamethasone use.

PMID- 29061464
TI  - The eighth edition TNM stage classification for lung cancer: What does it mean on
      main street?

PMID- 29061463
TI  - Presentation, Treatment, and Long-Term Outcome of Intrasellar Chordoma: A Pooled
      Analysis of Institutional, SEER (Surveillance Epidemiology and End Results), and
      Published Data.
AB  - BACKGROUND: Chordoma that occurs primarily in the sella turcica is rare and
      presents unique treatment challenges. OBJECTIVE: The purpose of this study was to
      determine common features, treatment approaches, and survival characteristics of
      intrasellar chordoma. METHODS: Institutional databases, the SEER (Surveillance
      Epidemiology and End Results) database, and PubMed/EMBASE were queried for
      chordoma with a primarily intrasellar component. The SEER database was also
      queried for adult skull base chordoma. Patient-level data were extracted where
      available. Kaplan-Meier survival analyses were conducted. RESULTS: Among 80
      cases, the mean age at presentation was 55.6 (standard deviation, 15.9), with a
      female predominance (1.16:1.00). Patients experienced symptoms for a mean
      duration of 19.0 months, including cranial nerve deficits, hypopituitarism, and
      hyperprolactinemia. Among patients receiving treatment, 77.5% underwent surgery.
      In addition, less than half of the patients (n = 34, 47.3%) received adjuvant
      radiation therapy. The 5-year overall survival (OS) of intrasellar chordoma was
      60.0% (standard error [SE], 6.9). Patients aged 40 years and younger had a 5-year
      OS of 80.8% (SE, 12.2), compared with patients older than 40 years, who had an OS
      of 55.4% (SE, 7.7) (Mantel-Cox, P = 0.044). Males experienced a lower 5-year OS
      (44.0; SE, 9.7) than did females (76.8; SE, 8.5), (Mantel-Cox, P = 0.003). Median
      OS was greater in patients with skull base chordoma than in patients with
      intrasellar chordoma (Mantel-Cox, P = 0.046). CONCLUSIONS: Intrasellar chordoma
      presents frequently with visual disturbances and hyperprolactinemia and has a
      slightly higher incidence in females. Young age predicts a better prognosis.
      Intrasellar chordoma has a lower overall survival than has skull base chordoma.

PMID- 29061462
TI  - Predicting Prognosis of Patients with Chronic Subdural Hematoma: A New Scoring
      System.
AB  - OBJECTIVE: Chronic subdural hematoma (CSDH) is a commonly encountered
      neurosurgical pathology that frequently requires operative intervention. With an
      increasing ageing demographic, more elderly and comorbid patients will present
      with symptomatic CSDH. This study evaluated clinical and radiologic factors to
      create a scoring system to aid prognostication. METHODS: A cohort of patients
      undergoing evacuation of CSDH at a single institution was established from 2010
      to 2015. Primary endpoint was a dichotomized score on a modified Rankin Scale
      score at 1-year follow-up (favorable outcome score 0-1; unfavorable outcome score
      2-6). Logistic regression analyses were performed to model determinants related
      to outcome. A prediction rule for diagnosing poor postoperative prognosis with
      unfavorable modified Rankin Scale score was developed with the obtained results.
      RESULTS: Logistic regression analyses showed that age >75 years, midline shift
      >10 mm, and hematoma thickness >30 mm were significantly associated with
      unfavorable outcome (age >75 years: odds ratio [OR] 0.01, 95% confidence interval
      [CI] 0.001-0.01; midline shift 11-20 mm: OR 0.18, 95% CI 0.04-0.88; midline shift
      >20 mm: OR 0.03, 95% CI 0.002-0.41; hematoma thickness >30 mm: OR 0.07, 95% CI
      0.01-0.46). A scoring system was designed using the final fitted multivariate
      model. A minimum score of 3 is feasible, indicating worst prognosis, and maximum
      score of 13 is feasible, indicating best prognosis. A score of >=9 showed
      favorable outcome. Receiver operating characteristic curves were constructed to
      predict favorable versus unfavorable outcomes with the sensitivity analysis
      yielding an excellent model discrimination with an area under curve of 0.95, 95%
      CI 0.92-0.98. CONCLUSIONS: A scoring system has been devised to predict outcome,
      which can aid in the necessity of surgery in certain patient demographics.

PMID- 29061465
TI  - Isolated and concomitant minimally invasive minithoracotomy aortic valve surgery.
AB  - OBJECTIVE: To evaluate whether the outcomes of minimally invasive aortic valve
      surgery were similar in younger versus older patient groups, as well as whether
      concomitant minimally invasive aortic valve replacement (AVR) surgeries added
      significant risks in these populations. METHODS: We performed a single
      institution retrospective analysis of 1018 patients undergoing isolated AVR and
      378 patients undergoing concomitant AVR procedures over a 6-year period. All
      surgeries were via a right minithoracotomy approach, and patients who underwent
      reoperation were excluded. RESULTS: Mortality was 1.3% in the isolated AVR group
      and 3.2% in the concomitant AVR group. The incidence of permanent stroke was low
      in both the isolated and concomitant AVR groups (0.8% and 1.1%, respectively). In
      both groups, femoral cannulation was associated with equally low stroke rates
      (0.8% and 0.6%, respectively). When analyzing operative outcomes by age,
      mortality was similar for the isolated AVR group (age <80 vs >=80 years, 0.9% vs
      2.2%; P = .07) and the concomitant AVR group (<80 vs >=80 years, 3.2% vs 3.2%; P
      = .99), whereas transfusion requirements, intensive care unit and hospital
      lengths of stay, and atrial fibrillation rates were greater in the older subsets
      of both AVR groups. CONCLUSIONS: Minimally invasive right thoracotomy AVR surgery
      was associated with low stroke and mortality rates in all age groups within 30
      days of surgery. Similarly, minithoracotomy concomitant AVR surgery demonstrated
      excellent results and is deemed feasible in patients with multiple pathologies.

PMID- 29061466
TI  - Gazing into the crystal ball: Preventing the inevitable shortage of
      cardiothoracic surgeons.

PMID- 29061467
TI  - An interactive simulation tool for patient-specific clinical decision support in
      single-ventricle physiology.
AB  - OBJECTIVE: Modeling of single-ventricle circulations has yielded important
      insights into their unique flow dynamics and physiology. Here we translated a
      state-of-the-art mathematical model into a patient-specific clinical decision
      support interactive Web-based simulation tool and show validation for all 3
      stages of single-ventricular palliation. METHODS: Via the adoption a validated
      lumped parameter method, complete cardiovascular-pulmonary circulatory models of
      all 3 stages of single-ventricle physiology were created within a simulation
      tool. The closed-loop univentricular heart model includes scaling for growth and
      respiratory effects, and typical patient-specific parameters are entered through
      an intuitive user interface. The effects of medical or surgical interventions can
      be simulated and compared. To validate the simulator, patient parameters were
      collected from catheterization reports. Four simulator outputs were compared
      against catheterization findings: pulmonary to systemic flow ratio (Qp:Qs),
      systemic arterial saturation (SaO2), mean pulmonary arterial pressure (mPAp), and
      systemic-venous oxygen difference (SaO2-SvO2). RESULTS: Data from 60 reports were
      used. Compared with the clinical values, the simulator results were not
      significantly different in mean Qp:Qs, SaO2, or mPAp (P > .09). There was a
      statistical but clinically insignificant difference in average SaO-SvO2 (average
      difference 1%, P < .01). Linear regression analyses revealed a good prediction
      for each variable (Qp:Qs, R2 = 0.79; SaO2, R2 = 0.64; mPAp, R2 = 0.69; SaO2-SvO2,
      R2 = 0.93). CONCLUSIONS: This simulator responds quickly and predicts patient
      specific hemodynamics with good clinical accuracy. By predicting postoperative
      and postintervention hemodynamics in all 3 stages of single-ventricle physiology,
      the simulator could assist in clinical decision-making, training, and
      consultation. Continuing model refinement and validation will further its
      application to the bedside.

PMID- 29061468
TI  - An Unusual Cause of Gastrointestinal Bleeding.

PMID- 29061469
TI  - Development and Evolution through the Lens of Global Gene Regulation.
AB  - Evolution and development are two inherently intertwined processes. As the embryo
      develops it does so in ways that both reflect past constraints and bias the
      future evolution of the species. While research exploiting this insight typically
      studies individual genes, transcriptomic analyses have sparked a new wave of
      discoveries. In this opinion piece, I review the evidence arising from
      transcriptomics on the topics of the evolution of germ layers, the phylotypic
      stage, and developmental constraints. The spatiotemporal pattern of gene
      expression across germ layers provides evidence that the endoderm was the first
      germ layer to evolve. Comparing transcriptome dynamics throughout developmental
      time across distant species reveals a mid-developmental transition under strong
      developmental constraints. These studies highlight the efficiency of exploratory
      data analysis using computational tools and comparative approaches for discovery.

PMID- 29061470
TI  - Injury to the inferior alveolar and lingual nerves in successful and failed
      coronectomies: systematic review.
AB  - The aim of this systematic review was to evaluate the incidence of damage to the
      inferior alveolar (IAN) and dental nerves in successful coronectomies, and to
      compare the results with coronectomies that failed. To the best of our knowledge
      no such analyses have been reported. Between January 1990 and October 2016 we
      surveyed published papers to find those that examined clinical outcomes after
      coronectomy. Fourteen met the criteria for final inclusion. Of 2087
      coronectomies, 152 failed (7%). Successful procedures were associated with a low
      overall incidence of injury to the IAN (0.5%) and lingual nerve (0.05%). The
      incidence of injury to the IAN in failed coronectomies was 2.6%. The incidence of
      permanent paraesthesia was 0.05% in successful coronectomies and 1.3% in those
      that failed. No permanent injury to the lingual nerve was reported. Mobility
      (36%, 55/152) and migration or exposure (33%, 50/152) of roots were the most
      common underlying causes of failure. Coronectomy seems to be safe, but it depends
      on the patient and the technique used. To ensure adequate assessment of
      postoperative complications, we strongly recommend systematic evaluation of the
      reduction in sensitivity of the lower lip, chin, or tongue, and a standard follow
      up.

PMID- 29061471
TI  - Re: Mandibular stability using sliding or conventional four-hole plates for
      fixation after bilateral sagittal split ramus osteotomy for mandibular setback.

PMID- 29061472
TI  - Quantification of steroid hormones in human serum by liquid chromatography-high
      resolution tandem mass spectrometry.
AB  - A limited specificity is inherent to immunoassays for steroid hormone analysis.
      To improve selectivity mass spectrometric analysis of steroid hormones by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) has been introduced in the
      clinical laboratory over the past years usually with low mass resolution triple
      quadrupole instruments or more recently by high resolution mass spectrometry (HR
      MS). Here we introduce liquid chromatography-high resolution tandem mass
      spectrometry (LC-MS/HR-MS) to further increase selectivity of steroid hormone
      quantification. Application of HR-MS demonstrates an enhanced selectivity
      compared to low mass resolution. Separation of isobaric interferences reduces
      background noise and avoids overestimation. Samples were prepared by automated
      liquid-liquid extraction with MTBE. The LC-MS/HR-MS method using a quadrupole
      Orbitrap analyzer includes eight steroid hormones i.e. androstenedione,
      corticosterone, cortisol, cortisone, 11-deoxycortisol, 17-hydroxyprogesterone,
      progesterone, and testosterone. It has a run-time of 5.3min and was validated
      according to the U.S. Food and Drug Administration (FDA) and the European
      Medicines Agency (EMA) guidelines. For most of the analytes coefficient of
      variation were 10% or lower and LOQs were determined significantly below 1ng/ml.
      Full product ion spectra including accurate masses substantiate compound
      identification by matching their masses and ratios with authentic standards. In
      summary, quantification of steroid hormones by LC-MS/HR-MS is applicable for
      clinical diagnostics and holds also promise for highly selective quantification
      of other small molecules.

PMID- 29061473
TI  - Optimization of ultra-high pressure liquid chromatography - tandem mass
      spectrometry determination in plasma and red blood cells of four sphingolipids
      and their evaluation as biomarker candidates of Gaucher's disease.
AB  - While important advances have been recently achieved in the optimization of lipid
      classes' separation, information on the specific determination of medium polarity
      lipids such as sphingolipids (SLs) in highly complex matrices remains
      fragmentary. In human, disorders of SL metabolism known as sphingolipidoses are a
      heterogeneous group of inherited disorders affecting primarily the central
      nervous. Early diagnosis of these conditions is of importance notably when a
      corrective therapy is available. The diagnosis is generally based on the
      determination of specific SLs in plasma and red blood cells (RBCs). For instance,
      glucosylceramide (GL1), glucosylsphingosine (Lyso-GL1), sphingosine (Sph), and
      sphingosine-1-phosphate (S1P) are proposed as relevant biomarkers for Gaucher
      disease (GD). Our main objective was to evaluate these biomarker candidates in a
      cohort of GD patients. However, most of current methods of GL1, Lyso-GL1, Sph,
      and S1P determination in plasma of GD patients require at least two liquid
      chromatographic runs. On the other hand, except for GL1 nothing is known
      concerning the RBC sphingolipid content. Yet, several reversed phase LC-MS
      methods of SLs separation and/or determination in various media with different
      sample preparation approaches have been proposed since 2010. Here we focused on
      stationary phase selection and mobile phase composition as well as on the sample
      preparation step to optimize and validate an UHPLC-MS/MS method for the
      simultaneous quantification of the four sphingolipids in both plasma and RBCs. A
      comparison between seven stationary phases including two RP18, two polar embedded
      RP18, and three HILIC phases shows that under our conditions polar embedded RP18
      phases are the most appropriate for the separation of the four SLs, in terms of
      efficiency, peak symmetry, and separation time. In the same way, a comparison
      between a single step extraction with methanol and a liquid-liquid extraction
      with a mixture of methanol/methyl tert-butyl ether, shows that the latter mixture
      is the most appropriate for the extraction of SLs in terms of recovery and
      absence of matrix effect. After validation, this method was applied to the
      evaluation of the targeted SLs in a cohort of 15 known GD patients. The obtained
      results show that Lyso-GL1 is the only relevant biomarker in both plasma and RBCs
      for GD diagnosis. As the proposed method is applicable to the determination in
      such a highly complex matrices of four SLs with a large difference in polarity,
      and as the sample preparation procedure is freedom of matrix effects, this method
      can be easily adapted to a large diversity of samples.

PMID- 29061474
TI  - Star-shaped oligothiophene-functionalized truxene materials as stationary phases
      for capillary gas chromatography.
AB  - This work reports oligothiophene-functionalized truxene-based stationary phases
      (TTT, TDT and TFT) with a unique star-shaped pi-conjugated architecture for gas
      chromatographic (GC) separations. They exhibited medium polarity and column
      efficiency of 3340-3760 plates/m determined by naphthalene at 120 degrees C.
      Among them, the TTT stationary phase displayed advantageous resolving capability
      over the TDT and TFT phases for a wide ranging analytes from apolar to polar,
      particularly for structural and positional isomers, including alcohols, phenols,
      halogenated and alkylated benzenes and naphthalenes. Moreover, the TTT column
      exhibited good thermal stability and repeatability with relative standard
      deviation (RSD) values of 0.02%-0.07% for run-to-run, 0.10%-0.53% for day-to-day
      and 2.1%-2.9% for column-to-column, respectively. In addition, it was applied for
      the determination of isomer impurities in real samples, proving its good
      potential for practical GC analysis.

PMID- 29061475
TI  - Characterization of organic aromatic compounds in soils affected by an
      uncontrolled tire landfill fire through the use of comprehensive two-dimensional
      gas chromatography-time-of-flight mass spectrometry.
AB  - Discarded vehicle tires have become an increasing concern worldwide due to the
      enormous amount of wastes generated and the increasing evidence of health
      problems associated to their disposal and accidental combustion. Previous studies
      conducted involving either simulated or open uncontrolled tire fires have
      identified aromatics belonging to two main classes, volatile organic compounds
      and polycyclic aromatic compounds (PAHs), as the most relevant chemicals
      generated in these burning processes. As a consequence, and due to their
      recognized toxicity, most studies reported up to now have mainly focused on these
      two categories of compounds being information concerning the possible occurrence
      of other aromatic classes rather limited. In this study, the enhanced separation
      power and structural confirmation capabilities provided by comprehensive two
      dimensional gas chromatography-time-of-flight mass spectrometry (GC*GC-ToF MS)
      has been used, for the first time, for the non-targeted analysis of soils
      impacted by a tire fire and an ash collected at the scene of the fire. In total,
      118 volatile and semi-volatile aromatic compounds have been differentiated. Among
      them, 104 compounds have been either positively or tentatively identified. PAHs
      with 3-5 rings and their alkyl-derivatives were the most numerous and relevant
      classes in the investigated samples. A significant number of sulfur, oxygen- and
      nitrogen-containing PAHs were also detected in the samples. The application of a
      script function to the raw GC*GC-ToF MS data allowed the fast filtering and
      automatic recognition of compounds containing halogens in their structure. This
      part of the study evidenced that only a limited number of regulated persistent
      organic pollutants were present in the investigated samples. However, it also
      revealed the presence of emerging organophosphorous flame retardants, whose
      levels in tire fire impacted soils are reported for the first time.

PMID- 29061476
TI  - Long-term changes of patient-reported quality of life after major trauma: The
      importance of the time elapsed after injury.
AB  - BACKGROUND: Numerous studies have identified various risk factors for a poor
      health-related quality of life (HRQOL) after severe trauma. The relative
      importance of the time elapsed after injury, however, is unknown and results of
      clinical studies have been conflicting. METHODS: A cross-sectional study was
      performed in two trauma centres using data from the German TraumaRegister DGU(r),
      which contained prospectively collected information on the type and severity of
      the injury, on critical care, and on outcome. To evaluate HRQOL in patients
      surviving more than 500days after the injury, we used a self-rating instrument,
      the EQ-5D which contains a visual analogue scale (EQ-VAS), and which allows the
      calculation of a global outcome indicator, the EQ-D5 index value. Complex
      statistical models were used to evaluate independent associations between the
      time elapsed after injury and a poor HRQOL. RESULTS: Of 380 contacted patients,
      follow-up assessments could be obtained in 168 patients (44.2%) 3.6+/-1.6 (SD)
      years after the injury. There was a linear association between the time elapsed
      after the injury and the% of contacted patients not participating in the study
      (p=0.013). In participating subjects, average EQ-5D index value was 0.599+/
      0.299, and average EQ-VAS rating 67.8+/-22.0. A very poor quality of life (EQ-5D
      index value<0.6, EQ-VAS rating<=50) could be found in 43.5% and 28.0% of the
      patients, respectively. After adjusting for multiple confounders, the number of
      days elapsed after injury showed a complex non-linear and independent association
      with a poor HRQOL (low EQ-5D index value: p=0.027; low EQ-VAS rating: p=0.008).
      Frequencies of a poor HRQOL reached their minimum about four to five years after
      the injury and increased thereafter. CONCLUSIONS: There is an independent, U
      shaped association between the frequency of extreme values of HRQOL and the time
      elapsed after injury. Time patterns of HRQOL may be sensitive to increasing rates
      of attrition since patients with a good outcome are less likely to respond to
      questionnaires. Time from injury should be incorporated into all future cross
      sectional studies trying to identify predictors of HRQOL.

PMID- 29061477
TI  - Effect of hypothermia on apoptosis in traumatic brain injury and hemorrhagic
      shock model.
AB  - INTRODUCTION: The neuroprotective mechanisms of therapeutic hypothermia against
      trauma-related injury have not been fully understood yet. In this study, we aimed
      to investigate the effects of therapeutic hypothermia on biochemical and
      histopathological markers of apoptosis using Traumatic brain injury (TBI) and
      hemorrhagic shock (HS) model. METHODS: A total of 50 male albino-wistar rats were
      divided into five groups: Group isolated TBI, Group NT (HT+HS+normothermia),
      Group MH (HT+HS+mild hypothermia), Group MoH (HT+HS+moderate hypothermia) and
      Group C (control). Neurological deficit scores were assessed at baseline and at
      24h. The rats were, then, sacrificed to collect serum and brain tissue samples.
      Levels of Caspase-3,6,8, proteoglycan-4 (PG-4), malondialdehyde (MDA), and nitric
      oxide (NO) were measured in serum and brain tissue samples. Histopathological
      examination was performed in brain tissue. RESULTS: There were significant
      differences in the serum levels of Caspase-3 between Group NT and Group C
      (p=0.018). The serum levels of Caspase-6 in Group NT (0.70+/-0.58) were lower
      than Group MH (1.39+/-0.28), although the difference was not statistically
      significant (p=0.068). There were significant differences in the brain tissue
      samples for Caspase-3 levels between Group NT and Group C (p=0.049). A
      significant difference in the Caspase-8 brain tissue levels was also observed
      between Group NT and Group C (p=0.022). Group NT had significantly higher scores
      of all the pathological variables (for edema p<0.017; for gliosis p<0.001; for
      congestion p<0.003, for hemorrhage p<0.011) than Group C. CONCLUSION: Our study
      results suggest that hypothermia may exert its neuroprotective effects by
      reducing markers of apoptotic pathway, particularly Caspase-3 on TBI and HS.

PMID- 29061478
TI  - Impact of dermatology eConsults on access to care and skin cancer screening in
      underserved populations: A model for teledermatology services in community health
      centers.
AB  - BACKGROUND: The clinical outcome of teledermatology with dermoscopy in large
      scale primary care networks remains unclear. OBJECTIVE: We evaluate the impact of
      implementing a teledermatology consultation program with dermoscopy on a
      statewide scale, focusing on access to care and skin cancer screening for
      medically underserved populations. METHODS: Descriptive retrospective cohort
      study of 2385 dermatology referrals from primary care from June 2014 through
      November 2015. RESULTS: Before implementation of electronic consultations
      (eConsults), access to dermatology was limited; only 139 (11%) of 1258 referrals
      resulted in a confirmed appointment with a median wait time of 77 days. Post
      implementation, 499 of 1127 consults (44%) were sent electronically, and of
      those, 16% required a face-to-face visit with a median wait time of 28 days. Ten
      malignancies were identified via eConsults. Overall consult volume remained
      stable pre- and post-eConsult implementation. LIMITATIONS: We evaluated eConsults
      in medically underserved populations seeking care at community health centers.
      Results might not be generalizable to other populations or in other settings.
      CONCLUSION: eConsults increase access to dermatologic care and reduce wait times
      for patients receiving medical care at community health centers. Implementing
      dermoscopy into teledermatology could increase access to skin cancer screening
      and treatment for medically disadvantaged populations.

PMID- 29061480
TI  - The Use of Magnetic Resonance Imaging to Predict Oncological Control Among
      Candidates for Focal Ablation of Prostate Cancer.
AB  - OBJECTIVE: To provide insights into the role of multiparametric magnetic
      resonance imaging (mpMRI) in predicting oncological control following 2 focal
      ablation (FA) templates for selective cases of prostate cancer. MATERIALS AND
      METHODS: A total of 59 radical prostatectomies were performed between 2012 and
      2016 on cases that fulfilled criteria for FA. The Gleason score (GS), extent of
      Gleason pattern (GP) 4, maximum linear cross-sectional length (MLCSL), and
      location of tumor foci were recorded and related to scale on corresponding 3-mm
      transverse slice prostate maps. Gleason pattern 4 extra-focal disease (GP4EFD)
      was defined as prostate cancer with any GP 4 not detected by mpMRI and
      transrectal ultrasound systematic biopsy observed outside a specified ablation
      zone. The location of these GP4EFD relative to the MRI lesion (MRI-L)
      (contralateral or ipsilateral) was recorded and used to predict oncological
      control following a hypothetical margin and ipsilateral hemi-ablation templates.
      RESULTS: Overall, 15 of 59 (25.4%) of the prostate specimens had at least 1
      GP4EFD. Of the total 20 GP4EFD, 7 of 20 (35%) were ipsilateral and 13 of 20 (65%)
      were contralateral to the MRI-L. Of the GP4EFD, 16 of 20 (80%), 2 of 20 (10%),
      and 2 of 20 (10%) were GS 3 + 4, GS 4 + 3, and GS 4 + 4, respectively. Of these
      GP4EFD, 10 of 20 (50%) exhibited an MLCSL <5 mm. Ablating only the MRI-L+10 mm or
      performing an ipsilateral hemi-ablation would leave residual GP4 in 14 of 59
      (23.7%) and 11 of 59 (18.6%) of cases, respectively. CONCLUSION: Because a
      significant proportion of candidates for FA based on mpMRI and systematic biopsy
      will have pre-existing GP4EFD outside ablation templates, active surveillance of
      the untreated prostate is mandatory.

PMID- 29061481
TI  - Palmitate-induced impairment of autophagy turnover leads to increased apoptosis
      and inflammation in peripheral blood mononuclear cells.
AB  - Previous works have linked high concentrations of palmitate to cellular toxicity
      by autophagy modulation. However, the ways in which palmitate regulates
      inflammation and apoptosis in peripheral blood mononuclear cells (PBMCs), has not
      been well characterized. In the present study, we therefore aimed to investigate
      the role autophagy in inflammatory responses and apoptotic death of PBMCs treated
      with palmitate. 0.5mM palmitate increased the level of LC3-II at 6h, peaked at
      12h and then decreased at 24h. The protein level of p62 was significantly
      increased at 6h and 12h, suggesting an impairment of autophagic flux in palmitate
      treated PBMCs. Inhibiting autophagy with chloroquine (CQ) and 3-Methyladenine (3
      MA) significantly augmented palmitate-induced PBMCs apoptotic death as
      demonstrated by increased cleaved PARP level and increased the percentage of
      apoptotic (YO-PRO-1 positive and PI negative) cells. Furthermore, CQ pretreatment
      exacerbated palmitate-induced TNF-alpha and IL-6 mRNA expression in PBMCs.
      Moreover, induction of autophagy by pretreatment of PBMCs with rapamycin resulted
      in a distinct increase of palmitate-induced apoptosis. The induction of autophagy
      also led to a further increase in palmitate-induced expression of TNF-alpha and
      IL-6. These results indicate that the excess palmitate could impair autophagy,
      hence contributing to palmitate-induced-inflammation and apoptosis in PBMCs.
      Therefore, dysregulated autophagy in PBMCs may provide a novel mechanism that
      connects diet-induced obesity to low grade inflammation in patients with type 2
      diabetes.

PMID- 29061479
TI  - Changing antimalarial agents after inefficacy or intolerance in patients with
      cutaneous lupus erythematosus: A multicenter observational study.
AB  - BACKGROUND: Changing from one antimalarial (AM) agent to another is often
      recommended in cutaneous lupus erythematosus (CLE) when the first AM agent is
      ineffective or poorly tolerated. OBJECTIVE: To evaluate the effect on cutaneous
      response of a switch from hydroxychloroquine to chloroquine, or the reverse,
      after failure of the first AM agent. METHODS: We conducted a retrospective
      observational study between 1997 and September 2015. The overall cutaneous
      response rate and reasons for failure of the switch were assessed for up to 48
      months. Kaplan-Meier survival curves were used to assess the risk for failure of
      the second AM agent. RESULTS: A total of 64 patients with CLE (78% were women)
      were included; for 48 patients, the switch was for inefficacy, and for 16, it was
      for adverse events. Median follow-up was 42 months (range, 3-171). Of the
      patients changed because of inefficacy, 56% were responders at month 3; however,
      the response decreased over time, with a median duration before failure of the
      second AM agent of 9 months (95% confidence interval, 6-24). For patients
      switched because of adverse events, the second AM agent was well tolerated in 69%
      of cases. LIMITATIONS: Retrospective design and subjective evaluation of
      cutaneous response. CONCLUSION: A change of AM agent should be considered in
      patients with CLE when the first AM agent is ineffective or poorly tolerated.

PMID- 29061482
TI  - IrC2/Bf - A yeast and Borrelia responsive component of the complement system from
      the hard tick Ixodes ricinus.
AB  - Ticks possess components of a primordial complement system that presumably play a
      role in the interaction of the tick immune system with tick-borne pathogens and
      affect their transmission. Here we characterized a novel complement component,
      tagged as IrC2/Bf, from the hard tick Ixodes ricinus, the principal vector of
      Lyme disease in Europe. IrC2/Bf is a multi-domain molecule composed of 5-7 CCP
      modules, varied by alternative splicing, followed by a von Willebrand factor A
      domain and a C-terminal trypsin-like domain. The primary structure and molecular
      architecture of IrC2/Bf displays the closest homology to the C3-complement
      component convertases described in horseshoe crabs. The irc2/bf gene is mainly
      expressed in the tick fat body associated with the trachea and, as determined by
      western blotting, the protein is present in low amounts in tick hemolymph.
      Expression of irc2/bf mRNA was significantly up-regulated in response to the
      intra-hemocoelic injection of the yeast Candida albicans and all tested Borrelia
      sp. strains (B. burgdorferi NE5264, B. burgdorferi CB26, B. garinii MSLB, B.
      afzelii CB43), but was not affected by injection of model Gram-negative and Gram
      positive bacteria or the aseptic injection control. In-line with these results,
      RNAi-mediated silencing of irc2/bf inhibited phagocytosis of B. afzelii and C.
      albicans but not the other bacteria. Tissue expression profiles, specific
      responses to microbial challenges, and patterns of phagocytic phenotypes upon
      RNAi silencing observed for IrC2/Bf match well with the previously reported
      characteristics of I. ricinus C3-related molecule 1 (IrC3-1). Therefore we
      presume that IrC2/Bf functions as a convertase in the same complement activation
      pathway protecting ticks against yeast and Borrelia infection.

PMID- 29061483
TI  - Current understanding of pattern-triggered immunity and hormone-mediated defense
      in rice (Oryza sativa) in response to Magnaporthe oryzae infection.
AB  - Plant pathogens represent a huge threat to world food security, affecting both
      crop production and quality. Although significant progress has been made in
      improving plant immunity by expressing key, defense-related genes and proteins
      from different species in transgenic crops, a challenge remains for molecular
      breeders and biotechnologists to successfully engineer elite, transgenic crop
      varieties with improved resistance against critical plant pathogens. Upon
      pathogen attack, including infection of rice (Oryza sativa) by Magnaporthe
      oryzae, host plants initiate a complex defense response at molecular, biochemical
      and physiological levels. Plants perceive the presence of pathogens by detecting
      microbe-associated molecular patterns via pattern recognition receptors, and
      initiate a first line of innate immunity, the so-called pattern-triggered
      immunity (PTI). This results in a series of downstream defense responses,
      including the production of hormones, which collectively function to fend off
      pathogen attacks. A variety of studies have demonstrated that many genes are
      involved in the defense response of rice to M. oryzae. In this review, the
      current understanding of mechanisms that improve rice defense response to M.
      oryzae will be discussed, with special focus on PTI and the phytohormones
      ethylene, jasmonic acid, salicylic acid, and abscisic acid; as well as on the
      mediation of defense signaling mechanisms by PTI and these hormones. Potential
      target genes that may serve as promising candidates for improving rice immunity
      against M. oryzae will also be discussed.

PMID- 29061484
TI  - Maximum power extraction under different vector-control schemes and grid
      synchronization strategy of a wind-driven Brushless Doubly-Fed Reluctance
      Generator.
AB  - This paper proposes an advanced strategy to synchronize the wind-driven Brushless
      Doubly-Fed Reluctance Generator (BDFRG) to the grid-side terminals. The proposed
      strategy depends mainly upon determining the electrical angle of the grid
      voltage, thetav and using the same transformation matrix of both the power
      winding and grid sides to ensure that the generated power-winding voltage has the
      same phase-sequence of the grid-side voltage. On the other hand, the paper
      proposes a vector-control (power-winding flux orientation) technique for maximum
      wind-power extraction under two schemes summarized as; unity power-factor
      operation and minimum converter-current. Moreover, a soft-starting method is
      suggested to avoid the employed converter over-current. The first control scheme
      is achieved by adjusting the command power-winding reactive power at zero for a
      unity power-factor operation. However, the second scheme depends on setting the
      command d-axis control-winding current at zero to maximize the ratio of the
      generator electromagnetic-torque per the converter current. This enables the
      system to get a certain command torque under minimum converter current. A sample
      of the obtained simulation and experimental results is presented to check the
      effectiveness of the proposed control strategies.

PMID- 29061485
TI  - Penalty boundary sequential convex programming algorithm for non-convex optimal
      control problems.
AB  - A nonlinear optimal control problem with non-convex cost function and non-convex
      state constraints can be addressed by a series of convex programming to obtain
      numerical solutions in previous methods. However, a feasible initial solution is
      essential to ensure the convergence. In this paper, slack variables are added
      into the model to handle the infeasible initial point and are penalized in the
      cost. What is more, a new approximation point on the boundary of constraints is
      embraced in each iteration to increase the similarity to original problem and
      decrease number of iterations. Thus, a penalty boundary sequential convex
      programming algorithm is proposed, which is globally convergent to a Karush-Kuhn
      Tucker (KKT) point of original problem under mild condition. The theoretical
      basis is guaranteed by a rigorous proof. Single UAV and multi-robots trajectory
      planning serve as simulations to verify the validity of the presented algorithm.

PMID- 29061486
TI  - Robust tracking and distributed synchronization control of a multi-motor
      servomechanism with H-infinity performance.
AB  - The multi-motor servomechanism (MMS) is a multi-variable, high coupling and
      nonlinear system, which makes the controller design challenging. In this paper,
      an adaptive robust H-infinity control scheme is proposed to achieve both the load
      tracking and multi-motor synchronization of MMS. This control scheme consists of
      two parts: a robust tracking controller and a distributed synchronization
      controller. The robust tracking controller is constructed by incorporating a
      neural network (NN) K-filter observer into the dynamic surface control, while the
      distributed synchronization controller is designed by combining the mean
      deviation coupling control strategy with the distributed technique. The proposed
      control scheme has several merits: 1) by using the mean deviation coupling
      synchronization control strategy, the tracking controller and the synchronization
      controller can be designed individually without any coupling problem; 2) the
      immeasurable states and unknown nonlinearities are handled by a NN K-filter
      observer, where the number of NN weights is largely reduced by using the minimal
      learning parameter technique; 3) the H-infinity performances of tracking error
      and synchronization error are guaranteed by introducing a robust term into the
      tracking controller and the synchronization controller, respectively. The
      stabilities of the tracking and synchronization control systems are analyzed by
      the Lyapunov theory. Simulation and experimental results based on a four-motor
      servomechanism are conducted to demonstrate the effectiveness of the proposed
      method.

PMID- 29061487
TI  - Design and implementation of a novel modal space active force control concept for
      spatial multi-DOF parallel robotic manipulators actuated by electrical actuators.
AB  - Robotic spine brace based on parallel-actuated robotic system is a new device for
      treatment and sensing of scoliosis, however, the strong dynamic coupling and
      anisotropy problem of parallel manipulators result in accuracy loss of
      rehabilitation force control, including big error in direction and value of
      force. A novel active force control strategy named modal space force control is
      proposed to solve these problems. Considering the electrical driven system and
      contact environment, the mathematical model of spatial parallel manipulator is
      built. The strong dynamic coupling problem in force field is described via
      experiments as well as the anisotropy problem of work space of parallel
      manipulators. The effects of dynamic coupling on control design and performances
      are discussed, and the influences of anisotropy on accuracy are also addressed.
      With mass/inertia matrix and stiffness matrix of parallel manipulators, a modal
      matrix can be calculated by using eigenvalue decomposition. Making use of the
      orthogonality of modal matrix with mass matrix of parallel manipulators, the
      strong coupled dynamic equations expressed in work space or joint space of
      parallel manipulator may be transformed into decoupled equations formulated in
      modal space. According to this property, each force control channel is
      independent of others in the modal space, thus we proposed modal space force
      control concept which means the force controller is designed in modal space. A
      modal space active force control is designed and implemented with only a simple
      PID controller employed as exampled control method to show the differences,
      uniqueness, and benefits of modal space force control. Simulation and
      experimental results show that the proposed modal space force control concept can
      effectively overcome the effects of the strong dynamic coupling and anisotropy
      problem in the physical space, and modal space force control is thus a very
      useful control framework, which is better than the current joint space control
      and work space control.

PMID- 29061488
TI  - Chemical synthesis of 7alpha-hydroxypregnenolone, a neuroactive steroid that
      stimulates locomotor activity.
AB  - 7alpha-Hydroxypregnenolone is an endogenous neuroactive steroid that stimulates
      locomotor activity. A synthesis of 7alpha-hydroxypregnenolone from pregnenolone,
      which takes advantage of an orthogonal protecting group strategy, is described.
      In detail, the C7-position was oxidized with CrO3 and 3,5-dimethylpyrazole to
      yield a 7-keto steroid intermediate. The resulting 7-ketone was stereoselectively
      reduced to the 7alpha-hydroxy group with lithium tri-sec-butylborohydride. In
      contrast, reduction of the same 7-ketone intermediate with NaBH4 resulted in
      primarily the 7beta-hydroxy epimer. Furthermore, in an alternative route to the
      target compound, the 7alpha-hydroxy group was successfully incorporated by direct
      C-H allylic benzoyloxylation of pregnenolone-3-acetate with CuBr and tert-butyl
      peroxybenzoate followed by saponification. The disclosed syntheses to 7
      oxygenated steroids are amenable to potentially obtain other biologically active
      sterols and steroids.

PMID- 29061489
TI  - Corticosteroid therapy exacerbates the reduction of melatonin in multiple
      sclerosis.
AB  - OBJECTIVES: Corticosteroid therapy is employed in multiple sclerosis (MS), a
      neurological abnormality characterized by an inflammatory process. Melatonin, a
      potent sleep-promoting and circadian phase regulatory hormone, is produced mainly
      in the pineal gland whose inhibition leads to sleep disturbances. METHODS: In
      this study, methylprednisolone (MP) corticosteroid treatment was used in an acute
      experimental autoimmune encephalomyelitis (EAE) rat model (intraperitoneal, 30
      mg/kg) and in MS patients (intravenous, 1000 mg/day), followed by assessing
      melatonin serum levels. KEY FINDINGS: Results showed that mean clinical scores
      were significantly improved in MP- versus PBS-treated EAE rats (1.5 vs 4.1,
      respectively). In addition, MP was found to induce a significant decrease in
      serum IFN-gamma, whereas IL-4 levels were significantly increased, in comparison
      to PBS-treated EAE rats. The ratio of IFN-gamma/IL-4, which acts as an indicator
      of Th-1/Th-2, was significantly lower in MP treated, compared to PBS treated EAE
      rats or controls. Moreover, serum levels of melatonin showed a significant
      decrease in the MP group, compared to normal rats. Moreover, MP therapy for 1 or
      2 days resulted in a significant reduction of melatonin serum levels in MS
      patients. CONCLUSIONS: Since corticosteroids cause a reduction in melatonin serum
      levels, an important hormone in sleep regulation, their prescription to MS
      patients should be carefully considered. Corticosteroids could be a cause of
      insomnia and sleep disturbance in patients receiving this type of medication.

PMID- 29061490
TI  - Electrophysiology of prosodic and lexical-semantic processing during sentence
      comprehension in aphasia.
AB  - Event-related potentials (ERPs) were used to examine how individuals with aphasia
      and a group of age-matched controls use prosody and themattic fit information in
      sentences containing temporary syntactic ambiguities. Two groups of individuals
      with aphasia were investigated; those demonstrating relatively good sentence
      comprehension whose primary language difficulty is anomia (Individuals with
      Anomic Aphasia (IWAA)), and those who demonstrate impaired sentence comprehension
      whose primary diagnosis is Broca's aphasia (Individuals with Broca's Aphasia
      (IWBA)). The stimuli had early closure syntactic structure and contained a
      temporary early closure (correct)/late closure (incorrect) syntactic ambiguity.
      The prosody was manipulated to either be congruent or incongruent, and the
      temporarily ambiguous NP was also manipulated to either be a plausible or an
      implausible continuation for the subordinate verb (e.g., "While the band played
      the song/the beer pleased all the customers."). It was hypothesized that an
      implausible NP in sentences with incongruent prosody may provide the parser with
      a plausibility cue that could be used to predict syntactic structure. The results
      revealed that incongruent prosody paired with a plausibility cue resulted in an
      N400-P600 complex at the implausible NP (the beer) in both the controls and the
      IWAAs, yet incongruent prosody without a plausibility cue resulted in an N400
      P600 at the critical verb (pleased) only in healthy controls. IWBAs did not show
      evidence of N400 or P600 effects at the ambiguous NP or critical verb, although
      they did show evidence of a delayed N400 effect at the sentence-final word in
      sentences with incongruent prosody. These results suggest that IWAAs have
      difficulty integrating prosodic cues with underlying syntactic structure when
      lexical-semantic information is not available to aid their parse. IWBAs have
      difficulty integrating both prosodic and lexical-semantic cues with syntactic
      structure, likely due to a processing delay.

PMID- 29061492
TI  - A synthetic, light-driven consortium of cyanobacteria and heterotrophic bacteria
      enables stable polyhydroxybutyrate production.
AB  - We previously reported that Synechococcus elongatus PCC 7942, engineered with the
      sucrose transporter CscB, can export up to 85% of its photosynthetically-fixed
      carbon as sucrose and shows considerable promise as an alternative carbohydrate
      source. One approach to effectively utilize this cyanobacterium is to generate
      synthetic, light-driven consortia in which sucrose-metabolizing heterotrophs
      catalyze the conversion of the low-value carbohydrate into higher-value compounds
      in co-culture. Here, we report an improved synthetic
      photoautotroph/chemoheterotroph consortial design in which sucrose secreted by S.
      elongatus CscB directly supports the bacterium Halomonas boliviensis, a natural
      producer of the bioplastic precursor, PHB. We show that alginate encapsulation of
      S. elongatus CscB enhances sucrose-export rates ~2-fold within 66h, to ~290mg
      sucrose L-1d-1 OD750-1 and enhances the co-culture stability. Consortial H.
      boliviensis accumulate up to 31% of their dry-weight as PHB, reaching
      productivities up to 28.3mg PHB L-1d-1. This light-driven, alginate-partitioned
      co-culture platform achieves PHB productivities that match or exceed those of
      traditionally engineered cyanobacterial monocultures. Importantly, S. elongatus
      CscB/H. boliviensis co-cultures were continuously productive for over 5 months
      and resisted invasive microbial species without the application of antibiotics or
      other chemical selection agents.

PMID- 29061493
TI  - Osteoarthritis year in review 2017: biology.
AB  - This Year in Review was derived from a personal selection of articles
      investigating biological mechanisms of osteoarthritis (OA) and presented at the
      OARSI World Congress on April 30, 2017. Selected articles were published between
      the March, 2016 and April, 2017 OARSI meetings. PubMed/MEDLINE searches were
      performed using the terms "osteoarthritis", "cartilage", "subchondral bone",
      "synovium", "synovitis", and "ageing". Biomechanical, genetic, genomic,
      epigenomic, biomarker, clinical, imaging, and tissue engineering studies were
      excluded since they are covered by other articles in this series. Several new and
      emerging themes were identified. Incorporating new technologies such as designer
      genetic engineering, nanotechnology, and bio-selective nuclear medicine tracers
      into study designs helps to gain important insights into OA pathophysiology.
      Potentially critical differences exist between biological mechanisms of post
      traumatic, age-associated, and metabolic phenotypes of OA. The concept of OA
      stages is highlighted, demonstrating how this may influence which biological
      mechanisms are at play and the need for strategic timing of treatment
      interventions. Not all inflammation is bad and fine-tuning a balance within
      inflammatory signaling mechanisms may be a path to regain joint homeostasis. Not
      only is the joint an organ system, sub-regions within each joint tissue,
      especially the joint lining, may play distinct roles in damage and repair. To
      accompany the review, the interaction among studies spanning multiple areas is
      summarized schematically.

PMID- 29061491
TI  - Neural mechanisms of mental fatigue elicited by sustained auditory processing.
AB  - Despite growing evidence that prolonged episodes of effortful listening can lead
      to mental fatigue, little work has been done to examine the patterns of brain
      activation associated with listening over time. In order to gain a better
      understanding of the nature of listening-related mental fatigue, this study
      characterized the effects of sustained auditory processing on brain activation in
      19 adults with normal hearing. A 50-min, auditory choice paradigm served as the
      fatiguing task. Mental fatigue was quantified using subjective (self-report) and
      behavioral (response time and accuracy) measures, as well as event-related
      potential (ERP) measures indexing motivation (error-related negativity; ERN) and
      general arousal (N1). Additional electrical neuroimaging analyses were carried
      out on ERP datasets. Subjective and behavioral results confirmed that
      participants became fatigued during the auditory task (data from the first 25min
      compared with the second 25min). ERPs revealed changes in neural activity
      consistent with decreased arousal (reduced N1 amplitude). Topographical analyses
      indicated decreased brain activation, without a change in underlying neural
      network configuration. Regions of decreased brain activation, as estimated via
      electrical neuroimaging, suggested a decrease in attention to task stimulus
      response characteristics (reduced activation in regions associated with the
      dorsal attention network). The decrease in mean N1 amplitude revealed a
      significant, positive correlation with subjective report of reduced motivation.
      These findings support existing cognitive and neurophysiological models that
      suggest mental fatigue builds over time on task, and affects motivation to
      influence task performance. Furthermore, this study shows sustained auditory
      processing can elicit mental fatigue, and that dorsal parietal activity might
      provide a useful method of measuring its effects.

PMID- 29061494
TI  - TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in
      rat nucleus pulposus cells.
AB  - OBJECTIVE: Hypoxia has been shown to inhibit reactive oxygen species (ROS)
      production in nucleus pulposus (NP) cells. The TP53-induced glycolysis and
      apoptosis regulator (TIGAR) has been reported to suppress oxidative stress. We
      sought to explore the role of TIGAR in the effect of hypoxia on ROS production
      and apoptosis. METHODS: An intervertebral disc degeneration (IDD) model of
      Sprague-Dawley (SD) rat caudal spine was established by puncturing the Co6-7
      disc. TIGAR expression was detected by immunohistochemistry and western blotting
      in human and SD rat NP tissues of degenerated discs. Rat primary NP cells treated
      with hypoxia and cobalt chloride (CoCl2) were analyzed by western blotting for
      TIGAR expression. After TIGAR silence with TIGAR siRNA transfection, apoptosis
      percentage, mitochondrial and total intracellular ROS levels were measured. H2O2
      was used to further check the effects of TIGAR on oxidative stress. Finally,
      NADPH/NADP+ and GSH/GSSH ratio were examined after TIGAR silencing under hypoxic
      conditions and after H2O2 treatment. RESULTS: A degree-dependent increase in
      TIGAR expression was observed in human and rat degenerated NP tissues. Hypoxia
      and hypoxia-inducer CoCl2 enhanced TIGAR and P53 expressions in rat NP cells.
      TIGAR silence reversed the inhibitory effects of hypoxia on intracellular and
      mitochondrial ROS production, as well as apoptosis percentage. However, TIGAR
      silence aggravated H2O2-induced ROS production. In addition, TIGAR increased
      NADPH/NADP+ and GSH/GSSH ratio in NP cells. CONCLUSIONS: These results suggested
      that TIGAR appears to mediate the protective role of hypoxia on ROS production
      and apoptosis percentage by enhancing NADPH/NADP+ and GSH/GSSH ratio.

PMID- 29061495
TI  - Femoral osteochondroplasty can be performed effectively without the risk of
      avascular necrosis or femoral neck fractures in an experimental ovine FAI model.
AB  - OBJECTIVE: The experimental induction of cam-type femoroacetabular impingement
      (FAI) in sheep is established. To tap the full potential of this ovine model, one
      should be able to perform a femoral osteochondroplasty safely. This study was
      based on previous cadaver experiments on the blood supply to the ovine femoral
      head and on the biomechanical strength of the proximal femur following offset
      creation. We hypothesized that offset creation in this ovine FAI model does not
      lead to (1) avascular necrosis (AVN) of the ovine femoral head or (2) iatrogenic
      femoral neck fractures and (3) can be performed effectively. DESIGN: In this
      experimental, controlled, prospective study nine sheep underwent unilateral FAI
      induction through an intertrochanteric, varus osteotomy. Seventy days following
      FAI induction, femoral osteochondroplasty was performed. Sheep were sacrificed
      after another 140 days. Radiographs, computed tomography (CT) scans and MRI were
      acquired. Histologic samples were stained with hematoxylin-eosin. (1) The
      multimodal Association Research Circulation Osseous (ARCO) classification was
      used for assessment of AVN. (2) Femoral neck fractures were assessed with the
      multimodal imaging approach. (3) Pre- and postoperative (=after sacrifice) alpha
      angles and femoral neck diameters were compared. RESULTS: (1) No signs for AVN
      according to the ARCO classification or (2) for femoral neck fractures were
      detected. (3) Mean alpha angles and femoral neck diameters decreased
      significantly (p < 0.001) superiorly by at least 30 degrees  respectively 4 mm
      after the offset creation. CONCLUSIONS: Femoral osteochondroplasty can be
      performed effectively and without the risk of AVN or femoral neck fractures in
      this ovine FAI model.

PMID- 29061497
TI  - Prospective clinical validation of independent DVH prediction for plan QA in
      automatic treatment planning for prostate cancer patients.
AB  - PURPOSE: To prospectively investigate the use of an independent DVH prediction
      tool to detect outliers in the quality of fully automatically generated treatment
      plans for prostate cancer patients. MATERIALS/METHODS: A plan QA tool was
      developed to predict rectum, anus and bladder DVHs, based on overlap volume
      histograms and principal component analysis (PCA). The tool was trained with 22
      automatically generated, clinical plans, and independently validated with 21
      plans. Its use was prospectively investigated for 50 new plans by replanning in
      case of detected outliers. RESULTS: For rectum Dmean, V65Gy, V75Gy, anus Dmean,
      and bladder Dmean, the difference between predicted and achieved was within 0.4
      Gy or 0.3% (SD within 1.8 Gy or 1.3%). Thirteen detected outliers were re
      planned, leading to moderate but statistically significant improvements (mean,
      max): rectum Dmean (1.3 Gy, 3.4 Gy), V65Gy (2.7%, 4.2%), anus Dmean (1.6 Gy, 6.9
      Gy), and bladder Dmean (1.5 Gy, 5.1 Gy). The rectum V75Gy of the new plans
      slightly increased (0.2%, p = 0.087). CONCLUSION: A high accuracy DVH prediction
      tool was developed and used for independent QA of automatically generated plans.
      In 28% of plans, minor dosimetric deviations were observed that could be improved
      by plan adjustments. Larger gains are expected for manually generated plans.

PMID- 29061498
TI  - Effect of a Red Blood Cell Transfusion on Biological Markers Used to Determine
      the Cause of Anemia: A Prospective Study.
AB  - BACKGROUND: Blood test results required for the evaluation of anemia are
      considered difficult to interpret after red blood cell transfusion. However, this
      hypothesis is neither supported by a strong physiological rationale nor is it
      evidence based. METHODS: We conducted a prospective multicenter study to compare
      the values of key assays prior to and after a course of red blood cell
      transfusion in the emergency or internal medicine units in 4 university
      hospitals. The following parameters were measured prior to and within 48 to 72
      hours after transfusion: complete blood count with reticulocyte count, direct
      Coombs' test, ferritin, transferrin saturation, soluble transferrin receptor,
      serum and erythrocyte folate, cobalamin, lactate dehydrogenase, bilirubin,
      haptoglobin, and C-reactive protein. We investigated the impact of transfusion on
      these parameters and assessed whether abnormal values prior to the transfusion
      became normal after transfusion (or conversely). RESULTS: There were 77 patients
      included in the study. Changes in mean values of mean corpuscular volume, soluble
      transferrin receptor, erythrocyte folate, cobalamin, haptoglobin, lactate
      dehydrogenase, C-reactive protein, and direct Coombs' test were not statistically
      significant. Changes in reticulocyte count, ferritin, transferrin saturation,
      serum folate, and total bilirubin concentrations were statistically significant,
      but they remained in the same diagnostic category (normal or abnormal) in 79% to
      98% of the cases; 97% of patients with iron deficiency still had low ferritin or
      transferrin saturation after a transfusion. CONCLUSION: Blood tests performed
      after a one-time red blood cell transfusion can be used to establish the cause of
      anemia when they have not been performed before.

PMID- 29061500
TI  - Are You Planning to Sign Up for a Trip to Mars? Extreme Environmental Health
      Consequences of Space Travel.

PMID- 29061501
TI  - The Seven Ages of the Physician.

PMID- 29061499
TI  - Reducing Inappropriate Testing for the Evaluation of Diarrhea Among Hospitalized
      Patients.
AB  - BACKGROUND: Diarrhea is one of the most common illnesses in the United States.
      Evaluation frequently does not follow established guidelines. The objective of
      this study was to evaluate the effectiveness of a computerized physician order
      entry-based test guidance algorithm with regard to the clinical, financial, and
      operational impacts. METHODS: Our population was patients with diarrheal illness
      at a tertiary academic medical center. The intervention was a computerized
      physician order entry-based test guidance algorithm that restricted the use of
      stool cultures and ova and parasites testing of diarrhea in the adult inpatient
      location vs nonintervention sites, which were the emergency department, pediatric
      inpatient and adult and pediatric outpatient locations. We measured stool
      culture, ova and parasites, and Clostridium difficile testing rates from July 1,
      2012 to January 31, 2016. Additionally, we calculated advisor usage, consults
      generated, accuracy of information, and cost savings. RESULTS: There was a
      significant decrease in stool culture and ova and parasites testing rates at the
      adult inpatient (P = .001 for both), pediatric (P < .001 for both), and adult
      emergency department (P < .001; P = .009) locations. The decrease at the
      intervention site was immediate, whereas the other locations showed a delayed but
      sustained decrease that suggests a collateral impact. A significant increase in
      the rate of stool culture and ova and parasites testing was observed in the
      outpatient setting (P = .02 and P = .001). We estimate that $21,931 was saved
      annually. CONCLUSIONS: A point-of-order test restriction algorithm for
      hospitalized adults with diarrhea reduced stool testing. Similar programs should
      be considered at other institutions and for the evaluation of other conditions.

PMID- 29061496
TI  - SDF-1/CXCR4 expression is an independent negative prognostic biomarker in
      patients with head and neck cancer after primary radiochemotherapy.
AB  - INTRODUCTION: Preclinical and clinical data suggest that the chemokine pathway
      governed by SDF-1 and CXCR4 contributes to a resistant phenotype. This
      retrospective biomarker study aims to explore the specific prognostic value of
      SDF-1 and CXCR4 expression in locally advanced head and neck squamous cell
      carcinomas (HNSCC) treated with primary radiochemotherapy (RT-CT). MATERIAL AND
      METHODS: Biopsies from 141 HNSCC tumours of the oral cavity, oropharynx and
      hypopharynx were evaluated for SDF-1 and CXCR4 expression by immunofluorescence.
      SDF-1 and CXCR4 expression was correlated with clinico-pathological
      characteristics and outcome after RT-CT. RESULTS: Patients with tumours
      exhibiting overexpression of intracellular SDF-1 and CXCR4 have a higher risk for
      loco-regional relapse and a worse overall survival after RT-CT (multivariate
      analysis, hazard ratio 2.33, CI [1.18-4.62], p = 0.02 and hazard ratio 2.02, CI
      [1.13-3.59], p = 0.02, respectively). Similar results were observed when only the
      subgroup of HPV DNA negative patients were analysed (hazard ratio 2.23 and 2.16,
      p = 0.02 and p = 0.01, respectively). CONCLUSIONS: Our data support the
      importance of SDF-1 and CXCR4 expression for loco-regional control and overall
      survival in HNSCC after primary radiochemotherapy. Prospective multivariate
      validation and further studies into CXCR4 inhibition to overcome radiation
      resistance are warranted.

PMID- 29061502
TI  - Organizing Pneumonia: Contemplate Beyond Cryptogenic.

PMID- 29061503
TI  - Outcomes in Severe Hyponatremia Treated With and Without Desmopressin.
AB  - BACKGROUND: Overcorrection of plasma sodium in severe hyponatremia is associated
      with osmotic demyelination syndrome. Desmopressin (DDAVP) can prevent
      overcorrection of plasma sodium in hyponatremia. The objective of this study was
      to compare outcomes in hyponatremia according to DDAVP usage. METHODS: This was a
      retrospective observational study including all admissions to internal medicine
      with hyponatremia (plasma sodium concentration <123 mEq/L) from 2004 to 2014 at 2
      academic hospitals in Toronto, Canada. The primary outcome was safe sodium
      correction (<=12 mEq/L in any 24-hour and <=18 mEq/L in any 48-hour period).
      RESULTS: We identified 1450 admissions with severe hyponatremia; DDAVP was
      administered in 254 (17.5%). Although DDAVP reduced the rate of change of plasma
      sodium, fewer patients in the DDAVP group achieved safe correction (174 of 251
      [69.3%] vs 970 of 1164 [83.3%]); this result was driven largely by overcorrection
      occurring before DDAVP administration in the rescue group. Among patients
      receiving DDAVP, most received it according to a reactive strategy, whereby DDAVP
      was given after a change in plasma sodium within correction limits (174 of 254
      [68.5%]). Suspected osmotic demyelination syndrome was identified in 4 of 1450
      admissions (0.28%). There was lower mortality in the DDAVP group (3.9% vs 9.4%),
      although this is likely affected by confounding. Length of stay in hospital was
      longer in those who received DDAVP according to a proactive strategy.
      CONCLUSIONS: Although observational, these data support a reactive strategy for
      using DDAVP in patients at average risk of osmotic demyelination syndrome, as
      well as a more stringent plasma sodium correction limit of 8 mEq/L in any 24-hour
      period for high-risk patients. Further studies are urgently needed on DDAVP use
      in treating hyponatremia.

PMID- 29061504
TI  - Genomic predictors of chemotherapy efficacy in advanced or recurrent gastric
      cancer in the GC0301/TOP002 phase III clinical trial.
AB  - Recent gastric cancer clinical trials have aimed to establish the efficacy of
      combination therapy over monotherapy, however, the role for genomic biomarkers in
      these trials has remained largely unexplored. Here, using the NanoString
      expression platform, we analyzed 105 gastric tumors from a randomized phase III
      Japanese clinical trial (GC0301/TOP002) testing the efficacy of irinotecan plus S
      1(IRI-S) versus S-1 therapy. We found that previously established proliferative
      subtype signatures, were associated with older patients (>65 years) and liver
      metastasis while mesenchymal subtype signatures were associated with younger
      patients (<=65 years) and peritoneal metastasis. Genes associated with tumor
      microenvironment (CD4, CD14, ADAMTS1, CCL5, CXCL12, CCL19), therapeutic
      implications (DPYD) and oncogenic signaling (Wnt5A, PTRF) were significantly
      associated with patient age, histology, tumor status, measurable lesions and
      metastasis. We identified Wnt5A downregulation as a candidate predictor of
      improved progression free survival (>8 weeks) in S-1 but not in IRI-S treatment.
      Although statistical significance was not achieved, mesenchymal subtype showed a
      trend for treatment interaction with IRI-S for efficacy. These findings highlight
      promising genomic markers that could be useful predictors of chemotherapy
      efficacy for better prognosis and survival outcome in gastric cancer.

PMID- 29061505
TI  - Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer
      invasion via the function of Endo180.
AB  - Specific cell populations leading the local invasion of cancer are called
      "leading cells". However, the underlying mechanisms are unclear. Here, we
      identified leading cells in pancreatic cancer and determined how these cells lead
      and promote cancer cell invasion in the extracellular matrix (ECM). Using three
      dimensional matrix remodeling assay, we found that pancreatic stellate cells
      (PSCs) frequently invaded the collagen matrix with pancreatic cancer cells
      (PCCs), which invaded behind the invading PSCs. In addition, invading PSCs
      changed the alignment of collagen fibers, resulting in ECM remodeling and an
      increase in the parallel fibers along the direction of invading PSCs. Endo180
      expression was higher in PSCs than in PCCs, Endo180 knockdown in PSCs attenuated
      the invasive abilities of PSCs and co-cultured PCCs, and decreased the expression
      level of phosphorylated myosin light chain 2 (MLC2). In mouse models, Endo180
      knockdown PSCs suppressed tumor growth and changes in collagen fiber orientation
      in co-transplantation with PCCs. Our findings suggest that PSCs lead the local
      invasion of PCCs by physically remodeling the ECM, possibly via the function of
      Endo180, which reconstructs the actin cell skeleton by phosphorylation of MLC2.

PMID- 29061506
TI  - Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem
      and non-stem cells.
AB  - Cancer stem-like cells (CSCs) contribute to tumor recurrence and chemoresistance.
      Hence, strategies targeting CSCs are crucial for effective anticancer therapies.
      Here, we demonstrate the capacities of the non-saponin fraction of Panax ginseng
      and its active principle panaxynol to inhibit Hsp90 function and viability of
      both non-CSC and CSC populations of NSCLC in vitro and in vivo. Panaxynol
      inhibited the sphere forming ability of NSCLC CSCs at nanomolar concentrations,
      and micromolar concentrations of panaxynol suppressed the viability of NSCLC
      cells (non-CSCs) and their sublines carrying acquired chemoresistance with
      minimal effect on normal cells derived from various organs. Orally administered
      panaxynol significantly reduced lung tumorigenesis in KrasG12D/+ transgenic mice
      and mice carrying NSCLC xenografts without detectable toxicity. Mechanistically,
      panaxynol disrupted Hsp90 function by binding to the N-terminal and C-terminal
      ATP-binding pockets of Hsp90 without increasing Hsp70 expression. These data
      suggest the potential of panaxynol as a natural Hsp90 inhibitor targeting both
      the N-terminal and C-terminal of Hsp90 with limited toxicities.

PMID- 29061507
TI  - MicroRNA-30a suppresses autophagy-mediated anoikis resistance and metastasis in
      hepatocellular carcinoma.
AB  - MiRNA-30a (miR-30a) was previously reported as one of metastatic hepatocellular
      carcinoma (HCC)-related microRNAs. However, the function of miR-30a on enhancing
      our biological understanding of HCC metastasis is not clear. This study
      demonstrated that miR-30a was significantly down-regulated in HCC tissues and
      cell lines, and was associated with vascular invasion, metastasis potential and
      recurrent disease in HCC. Functional studies confirmed that miR-30a could inhibit
      the metastasis of HCC in a well-established nude mouse model of lung metastasis.
      Moreover, miR-30a was proved to prevent anoikis inhibition of HCC cells in vivo
      and in vitro. Mechanically, autophagy related protein Beclin 1 and Atg5 were
      direct downstream targets of miR-30a, and mediated autophagy activity influence
      of miR-30a in HCC. Taken together, downregulated miR-30a in metastatic HCC
      mediates Beclin 1 and Atg5-dependent autophagy, which confers anoikis resistance
      in HCC cells. The molecular basis of autophagy action during this process partly
      contributes to the HCC metastasis, suggesting that targeting autophagy via miR
      30a may have therapeutic implications for the prevention of HCC
      recurrence/metastasis.

PMID- 29061508
TI  - Endogenous glutamate within the prelimbic and infralimbic cortices regulates the
      incubation of cocaine-seeking in rats.
AB  - The incubation of cue-reinforced cocaine-seeking coincides with increased
      extracellular glutamate within the ventromedial prefrontal cortex (vmPFC). The
      vmPFC is comprised of two subregions that oppositely regulate drug-seeking, with
      infralimbic (IL) activity inhibiting, and prelimibic (PL) activity facilitating,
      drug-seeking. Thus, we hypothesized that increasing and decreasing endogenous
      glutamate within the IL would attenuate and potentiate, respectively, cue
      reinforced drug-seeking behavior, with the converse effects observed upon
      manipulations of endogenous glutamate within the PL. Male Sprague-Dawley rats
      were trained to self-administer cocaine (0.25 mg/infusion; 6 h/day X 10 days),
      the delivery of which was signaled by a tone-light cue. Rats were then subdivided
      into 3 or 30 day withdrawal groups. For testing, rats were microinjected with
      vehicle, 20 mM of the mGlu2/3 agonist LY379268 (to lower endogenous glutamate),
      or 300 MUM of the excitatory amino acid transporter inhibitor threo-beta
      benzyloxyaspartate (TBOA; to raise endogenous glutamate) into either the IL or PL
      (0.5 MUl/side) and then given a 30-min test for cue-reinforced drug-seeking.
      Vehicle-infused rats exhibited incubated responding on the cocaine-associated
      lever. Neither LY379268 nor TBOA altered behavior at 3 days withdrawal,
      indicating that glutamate within neither subregion regulates cue-reinforced drug
      seeking during early withdrawal. At 30 days withdrawal, intra-PL LY379268
      microinjection significantly decreased drug-seeking behavior, while the effect
      was more modest when infused intra-IL. Interestingly, intra-IL TBOA attenuated
      incubated drug-seeking during protracted withdrawal, but did not affect behavior
      when infused intra-PL. These results argue that glutamate release within the PL
      in response to drug-seeking likely drives the manifestation of incubated cocaine
      seeking during protracted withdrawal.

PMID- 29061510
TI  - In vivo comparisons of silver nanoparticle and silver ion transport after
      intranasal delivery in mice.
AB  - Silver nanoparticles (AgNPs) are widely available as consumer goods, and over-the
      counter or nutraceutical products used for alleged therapeutic and antibacterial
      properties. Among these products, AgNP topical therapy is proposed for treating
      patients with upper airway bacterial rhinosinusitis. While silver ion release
      from AgNPs in biological systems is well known, limited investigations actually
      characterize this silver ion release and their subsequent biological effects
      distinct from delivered particulate metallic silver. This is in part due to the
      analytical complexity and difficulty involved in distinguishing silver ion
      release from metallic AgNPs in biological media. Therefore, this study compared
      intranasal administration of AgNPs versus soluble silver ion (AgNO3) control to
      examine their transport and biological differences in tissues. First, we compared
      bactericidal activities of AgNPs and AgNO3 in those bacteria commonly associated
      with clinical rhinosinusitis in vitro. Next, we evaluated silver residence time
      in the sinus cavity after intranasal delivery of AgNPs and AgNO3 to mice, and
      characterized tissue distribution of silver in the sinonasal mucosal epithelium.
      We found that AgNPs show reduced bactericidal activity compared to AgNO3 (i.e.,
      MBC of 15ppm compared to 5ppm), and significantly lower residence times in the
      sinus cavity (AgNP concentrations of 3.76ppm after 3h compared to 9ppm for
      AgNO3). AgNPs were not readily taken up into or through respiratory epithelium,
      with very low silver levels found in blood and no detectable silver measured in
      the olfactory bulb and brain. Results indicate that limited tissue distribution
      of silver detected from AgNPs is due to AgNP dissolution to silver ion. AgNPs
      therefore demonstrate adequate safety through limited penetration and absorption,
      but limited potential therapeutic efficacy as antimicrobials in nasal
      applications, as concentrations of silver in the sinus cavity drop below the
      minimum bactericidal concentration within 3h.

PMID- 29061509
TI  - Monoacylglycerol lipase inhibitor JZL184 prevents HIV-1 gp120-induced synapse
      loss by altering endocannabinoid signaling.
AB  - Monoacylglycerol lipase (MGL) hydrolyzes 2-arachidonoylglycerol to arachidonic
      acid and glycerol. Inhibition of MGL may attenuate neuroinflammation by enhancing
      endocannabinoid signaling and decreasing prostaglandin (PG) production. Almost
      half of HIV infected individuals are afflicted with HIV-associated neurocognitive
      disorder (HAND), a neuroinflammatory disease in which cognitive decline
      correlates with synapse loss. HIV infected cells shed the envelope protein gp120
      which is a potent neurotoxin that induces synapse loss. Here, we tested whether
      inhibition of MGL, using the selective inhibitor JZL184, would prevent synapse
      loss induced by gp120. The number of synapses between rat hippocampal neurons in
      culture was quantified by imaging clusters of a GFP-tagged antibody-like protein
      that selectively binds to the postsynaptic scaffolding protein, PSD95. JZL184
      completely blocked gp120-induced synapse loss. Inhibition of MGL decreased gp120
      induced interleukin-1beta (IL-1beta) production and subsequent potentiation of
      NMDA receptor-mediated calcium influx. JZL184-mediated protection of synapses was
      reversed by a selective cannabinoid type 2 receptor (CB2R) inverse
      agonist/antagonist. JZL184 also reduced gp120-induced prostaglandin E2 (PGE2)
      production; PG signaling was required for gp120-induced IL-1beta expression and
      synapse loss. Inhibition of MGL prevented gp120-induced synapse loss by
      activating CB2R resulting in decreased production of the inflammatory cytokine IL
      1beta. Because PG signaling was required for gp120-induced synapse loss, JZL184
      induced decreases in PGE2 levels may also protect synapses. MGL presents a
      promising target for preventing synapse loss in neuroinflammatory conditions such
      as HAND.

PMID- 29061511
TI  - Multifunctional nanoparticles co-delivering EZH2 siRNA and etoposide for
      synergistic therapy of orthotopic non-small-cell lung tumor.
AB  - Malignant proliferation and metastasis in non-small cell lung carcinoma (NSCLC)
      are great challenges for effective clinical treatment through conventional
      chemotherapy. The combinational therapy strategy of RNA interfering (RNAi)
      technology and chemotherapeutic agents have been reported to be promising for
      effective cancer therapy. In this study, based on multifunctional nanoparticles
      (NPs), the simultaneous delivery of etoposide (ETP) and anti-Enhancer of Zeste
      Homologue 2 (EZH2) siRNA for the effective treatment of orthotopic lung tumor was
      achieved. The NPs exhibited pH/redox dual sensitivity verified by particle size
      changes, morphological changes, and in vitro release of drugs. Confocal
      microscopy analysis confirmed that the NPs exhibited endosomal escape property
      and on-demand intracellular drug release behavior, which can protect siRNA from
      degradation and facilitate the chemotherapeutic effect respectively. In vitro
      tumor cell motility study demonstrated that EZH2 siRNA loaded in NPs can decrease
      the migration and invasion capabilities of tumor cells by downregulating the
      expression of EZH2 mRNA and protein. In particular, an antiproliferation study
      revealed that the co-delivery of siRNA and ETP in the multifunctional NPs can
      induce a synergistic therapeutic effect on NSCLC. In vivo targeting evaluation
      showed that cRGDyC-PEG modification on NPs exhibited a low distribution in normal
      organs and an obvious accumulation in orthotopic lung tumor. Furthermore,
      targeted NPs co-delivering siRNA and ETP showed superior inhibition on tumor
      growth and metastasis and produced minimal systemic toxicity. These findings
      indicated that multifunctional NPs can be utilized as a co-delivery system, and
      that the combination of EZH2 siRNA and ETP can effectively treat NSCLC.

PMID- 29061513
TI  - Rational designing of an antidote nanoparticle decorated with abiotic polymer
      ligands for capturing and neutralizing target toxins.
AB  - Many of macromolecular toxins induce cell death by directly interacting with
      cells or induction of inflammatory cytokines. Abiotic polymer ligands (PLs)
      composed of functional monomers are able to bind and neutralize toxins in vivo
      and are of great interest for efficient antidotes. However, little has been
      reported about recognition and neutralization of target molecules in the
      bloodstream because of readily elimination from the bloodstream. Here, we report
      a rational design of PLs-decorated lipid nanoparticles (PL-NPs) for neutralizing
      a target toxin in vivo. PL that decorated on the NPs would cooperatively
      interacts with target biomacromolecules since the lipid molecules in NPs have a
      high degree of freedom. In the present study, N-isopropylacrylamide based PLs
      interacting with histones, major mediators of sepsis, were synthesized. Affinity
      between PL-NPs and histones depends on monomer composition and polymer length.
      The optimized PL-NP showed little affinity for plasma proteins. The PL-NPs
      inhibited the toxicity of histones both in vitro and in vivo, suggesting that PLs
      on the NPs cooperatively bound to histones and neutralized their toxicity. In
      addition, circulation time of optimized PL was significantly prolonged by the
      modification onto NPs. These results provide a platform for designing antidote
      nanoparticles neutralizing toxic biomacromolecules.

PMID- 29061514
TI  - BOLD-MRI demonstrates acute placental and fetal organ hypoperfusion with fetal
      brain sparing during hypercapnia.
AB  - INTRODUCTION: We evaluated changes in placental and fetal hemodynamics in rodents
      during acute hypercapnia using BOLD-MRI and Doppler ultrasound. METHODS: Animals
      were anesthetized with pentobarbital and, in consecutive 4-min periods, breathed:
      air, 21%O2:5%CO2, and 95%O2:5%CO2. BOLD-MRI: Pregnant ICR mice (n = 6; E17.5)
      were scanned in a 4.7-T Bruker Biospec spectrometer. Placenta and fetal liver,
      heart and brain were identified on True-FISP images. Percent change in signal
      intensity (SI) were analyzed every 30 s from T2*-weighted GE images (TR/TE =
      147/10 ms). Doppler: Pregnant Wistar rats (n = 6; E18-20) were anesthetized with
      pentobarbital and received abdominal Doppler ultrasound. Umbilical artery
      pulsatility index (PI) and fetal heart rate were assessed at baseline and after
      two minutes of both hypercapnic challenges. RESULTS: BOLD-MRI: Normoxic
      hypercapnia caused immediate marked reduction in SI in placenta (-44% +/- 5.5; p
      < 0.001), fetal liver (-32% +/- 6.4; p < 0.001) and fetal heart (-53% +/- 9.9; p
      < 0.001) but only minor changes in fetal brain (-13% +/- 3.4; p < 0.01),
      suggesting fetal brain sparing. Doppler: Normoxic-hypercapnia caused a marked
      increase in umbilical artery PI (+27.4% +/- 7.2; p < 0.001) and a reduction in
      fetal heart rate (-48 bpm; 95%CI -9.3 to -87.0; p = 0.02), suggesting acute fetal
      asphyxia. CONCLUSIONS: Brief maternal hypercapnic challenge caused BOLD-MRI
      changes consistent with acute placental and fetal hypoperfusion with fetal brain
      sparing. The same challenge caused increased umbilical artery PI and fetal
      bradycardia on Doppler ultrasound, suggestive for acute fetal asphyxia. BOLD-MRI
      may be a suitable noninvasive imaging strategy to assess placental and fetal
      organ hemodynamics.

PMID- 29061515
TI  - Reply to: "Acid-base disorders in liver disease".

PMID- 29061512
TI  - Injectable hydrogels for ophthalmic applications.
AB  - The demand for effective eye therapies is driving the development of injectable
      hydrogels as new medical devices for controlled delivery and filling purposes.
      This article introduces the properties of injectable hydrogels and summarizes
      their versatile application in the treatment of ophthalmic diseases, including
      age-related macular degeneration, cataracts, diabetic retinopathy, glaucoma, and
      intraocular cancers. A number of injectable hydrogels are approved by FDA as
      surgery sealants, tissue adhesives, and are now being investigated as a vitreous
      humor substitute. Research on hydrogels for drug, factor, nanoparticle, and stem
      cell delivery is still under pre-clinical investigation or in clinical trials.
      Although substantial progress has been achieved using injectable hydrogels, some
      challenging issues must still be overcome before they can be effectively used in
      medical practice.

PMID- 29061516
TI  - Acid-base disorders in liver disease.

PMID- 29061517
TI  - NAFLD and cancer: More cause for concern?

PMID- 29061518
TI  - Investigation on human serum albumin and Gum Tragacanth interactions using
      experimental and computational methods.
AB  - The study on the interaction of human serum albumin and Gum Tragacanth, a
      biodegradable bio-polymer, has been undertaken. For this purpose, several
      experimental and computational methods were used. Investigation of thermodynamic
      parameters and mode of interactions were carried out using Fluorescence
      spectroscopy in 300 and 310K. Also, a Fourier transformed infrared spectra and
      synchronous fluorescence spectroscopy was performed. To give detailed insight of
      possible interactions, docking and molecular dynamic simulations were also
      applied. Results show that the interaction is based on hydrogen bonding and van
      der Waals forces. Structural analysis implies on no adverse change in protein
      conformation during binding of GT. Furthermore, computational methods confirm
      some evidence on secondary structure enhancement of protein as a presence of
      combining with Gum Tragacanth.

PMID- 29061519
TI  - A novel reverse micellar purification strategy for histidine tagged human
      interferon gamma (hIFN-gamma) protein from Pichia pastoris.
AB  - In the present study, we have demonstrated the process development of human
      interferon gamma (hIFN-gamma) (upstream to downstream). The codon optimized hIFN
      gamma gene was cloned in Pichia pastoris X-33 and the expression was evaluated in
      batch reactor study. The purification was carried out with modified nickel
      chelated reverse micellar system and compared with the existing Nickle-
      Nitrilotriacetic acid (NI-NTA) method. The parameter optimization for forward
      extraction demonstrated a significant enhancement of 72% in forward extraction
      efficiency (FEE). Furthermore, the factors governing back extraction efficiency
      (BEE) were also optimized with sequential optimization involving Taguchi
      orthogonal array and Artificial Neural Network linked Simulated Annealing
      Algorithm (ANN-SA). The optimization resulted in 91.2% back extraction efficiency
      of recombinant human interferon gamma (rhIFN-gamma). The development of this
      purification system with optimized parameters led to an efficient recovery of
      67.3% and improved purity of 79.54%. Alongside, the anti-proliferative activity
      in MCF-7 cell lines were also investigated and it demonstrated that at 60ngmL-1
      concentration of rhIFN-gamma more that 25%.

PMID- 29061521
TI  - Effect of heparan sulfate mimetics from Escherichia coli K5 polysaccharide on SDF
      1/CXCL12-induced endothelial progenitor cells in vitro.
AB  - In tumorigenesis, CXCL12 level increases sharply because of tumor tissue hypoxia.
      As CXCR4 cells, endothelial progenitor cells (EPCs) are mobilized to tumor bed
      through the CXCL12/CXCR4 axis and are involved in tumor angiogenesis. In this
      process, either glycosaminoglycan (GAG) or heparan sulfate (HS) carried by
      membrane proteoglycans is implicated. Exogenous soluble HS mimetics can act as a
      competitive inhibitor of membranous HS, thereby preventing the formation of a
      normal signal axis. In this work, the effect of HS mimetics on the CXCL12-induced
      EPCs in vitro was investigated. HS mimetics, named as K5PSs, were obtained from
      sulfated Escherichia coli K5 polysaccharide/heparosan, and EPCs were collected
      from rat bone marrow. Results showed that CXCL12 could promote EPCs viability.
      This promotion might be related to its regulation of cell cycle and anti
      apoptosis activity; it also could promote EPCs migration and secretion of pro
      angiogenesis factors. All its functions were obtained by activation of MAPK/ERK
      pathway, FAK pathway, and PI3k/AKT pathway. However, its effect on EPCs was
      attenuated by K5PSs, and the existence of sulfate groups both at 2-O-position and
      N-position in K5PSs is essential to inhibit its effect on EPCs. This work
      suggested that K5PSs could be applied in anti-tumor treatment through inhibiting
      tumor angiogenesis.

PMID- 29061520
TI  - Understanding the adhesion mechanism of a mucin binding domain from Lactobacillus
      fermentum and its role in enteropathogen exclusion.
AB  - Lactobacillus species possesses surface exposed Mucin Binding Protein (MucBP)
      which plays a role in adhesion to gastrointestinal mucin. MucBP contains one or
      more mucin binding domain (MBD), the functionality of which has yet not been
      characterized thoroughly. Here, we have characterized a 93-amino acid MBD (MBD93)
      of MucBP (LAF_0673) from Lactobacillus fermentum. Multiple sequence alignment of
      L. fermentum MBD93 exhibited ~60% sequence homology with MBDs from other
      Lactobacillus species. Further, we cloned, expressed and purified MBD93 from
      Escherichia coli as N-terminal histidine-tagged protein (6X His-MBD93). The
      purified MBD93 was able to bind to mucin and showed strong affinity towards the
      terminally expressed mucin glycans viz. N-acetylgalactosamine (GalNAc), N
      acetylglucosamine (GlcNAc), Galactose (Gal), and Sialic acid (N-acetylneuraminic
      acid; Neu5Ac). In silico experiments further confirmed the interaction between
      homology modeled MBD93 to mucin glycans through hydrogen-bonding with its surface
      amino acid residues Ser57, Pro58, Ile60, Tyr63 and Ala65. We also have
      demonstrated that MBD93 was able to inhibit the adhesion of enteric pathogens,
      including E. coli, Salmonella Paratyphi A, Shigella sonnei and Proteus vulgaris
      to mucin. Our results suggested that L. fermentum MBD93 is a functionally
      sufficient unit to act as an adhesin and to protect from invading enteric
      pathogens.

PMID- 29061523
TI  - Behavioral impairments following repeated intranasal glyphosate-based herbicide
      administration in mice.
AB  - Inhalation or intranasal (IN) administration of neurotoxicants could constitute a
      route of toxin delivery to the brain. Pesticides have been proposed as the main
      environmental factor associated with the etiology of neurodegenerative disorders.
      In Argentina, the area used for glyphosate (Gly)-resistant crops are sprayed
      annually with ~200 million liters of Gly-based herbicides (Gly-BHs). Gly residues
      are often found in the environment, and considering the frequency and amount of
      its applications, it is probable that the inhalation of Gly-BHs occurs. The
      present study investigates the neurobehavioral effects of repeated IN
      administration of Gly-BH in male CF-1 mice (~2mg/nostrils/day) three days a week,
      during four weeks (50mg/kg/day). Locomotor activity and anxiety levels were
      studied by the Open Field (OF) test. Anxiety was also analyzed through the plus
      maze (PM) test. Novel Object Recognition (NOR) test was used for recognition
      memory analysis. Repeated IN Gly-BH administration in mice decreased the
      ambulatory activity. Moreover, Gly-BH treated mice showed a pronounced increase
      in thigmotaxis, compared to control group, indicating higher anxiety levels. The
      anxiogenic behavior in Gly-BH treated mice was then confirmed by PM test. The
      recognition memory was significantly impaired after 6h in the Gly-BH treated
      group. No differences were observed between both groups when the NOR test was
      performed 24h after. The present study reveals that repeated IN exposure to Gly
      BH in mice affects the central nervous system probably altering neurotransmission
      pathways that participate or regulate locomotor activity, anxiety and memory.

PMID- 29061522
TI  - Prognostic value of fluorine-18 fluoro-2-deoxyglucose positron emission computed
      tomography in patients with unexplained atrioventricular block.
AB  - BACKGROUND: The cause of atrioventricular conduction block (AVB) remains
      unexplained in a significant number of patients. Granulomatous myocarditis is an
      uncommon but important cause of AVB. Fluorine-18 fluoro-2-deoxyglucose positron
      emission computed tomography (18-FDG PET) scan has emerged as a sensitive tool
      for diagnosing granulomatous myocarditis. OBJECTIVE: The purpose of this study
      was to evaluate the prognostic value of 18-FDG PET scan in patients with
      unexplained AVB. METHODS: Patients age 18-55 years presenting with unexplained
      AVB and requiring a permanent pacemaker were evaluated with a fasting 18-FDG PET
      scan. Transthoracic echocardiography was performed at baseline and at follow-up.
      Major adverse cardiac events (ventricular tachycardia, heart failure, cardiac
      death) were noted during follow-up. RESULTS: Over a period of 3 years, 35
      patients (20 females, 15 males; mean age 43.67 +/- 11.21 years) were included in
      the study. Abnormal myocardial FDG uptake was noted in 15 patients (42.8%). Four
      patients consented for biopsy of paracardiac FDG avid lymph nodes, which revealed
      granulomatous inflammation (one of which grew Mycobacterium tuberculosis in
      culture). Mean follow-up period was 24 months. Major adverse cardiac events were
      significantly higher in the patients with abnormal PET uptake (P < .01) compared
      to those with normal scans. CONCLUSION: Patients with high-degree AVB and
      abnormal myocardial 18-FDG PET uptake have more adverse cardiac events and worse
      outcomes. Early screening for myocardial inflammation and appropriate treatment
      may prevent these complications. Tuberculosis may be an important cause of
      unexplained AVB, apart from sarcoidosis, in developing countries such as India.

PMID- 29061524
TI  - Exogenous salicylic acid improves freezing tolerance of spinach (Spinacia
      oleracea L.) leaves.
AB  - Salicylic acid (SA)-treatment has been reported to improve plant tolerance to
      various abiotic stresses. However, its effect on freezing tolerance has not been
      well investigated. We investigated the effect of exogenous SA on freezing
      tolerance of spinach (Spinacia oleracea L.) leaves. We also explored if nitric
      oxide (NO) and/or hydrogen peroxide (H2O2)-mediation was involved in this
      response, since these are known as primary signaling molecules involved in many
      physiological processes. A micro-centrifuge tube-based system used to apply SA to
      petiolate spinach leaves (0.5 mM over 4-d) was effective, as evident by SA
      content of leaf tissues. SA-treatment did not hamper leaf growth (fresh and dry
      weight; equatorial and longitudinal length) and was also not significantly
      different from 25% Hoagland controls vis-a-vis growth. SA application
      significantly improved freezing tolerance as evidenced by reduced ion-leakage and
      alleviated oxidative stress (lower accumulation of O2.- and H2O2) following
      freeze-thaw stress treatments (-6.5, -7.5, and -8.5  degrees C). Improved
      freezing tolerance of SA-treated leaves was paralleled by increased proline and
      ascorbic acid (AsA) accumulation. A 9-d cold acclimation (CA) treatment also
      improved leaf freezing tolerance (compared to non-acclimated control) and was
      accompanied by accumulation of SA and proline. Our results indicate that
      increased freezing tolerance may be associated with accumulation of compatible
      solutes (proline) and antioxidants (AsA). Notably, the beneficial effect of SA on
      freezing tolerance was abolished when either H2O2- or NO-scavenger (1 MUM N
      acetylneuraminic acid, NANA or 100 MUM hemoglobin, HB, respectively) was added to
      SA as pretreatment. Our data suggest that SA-induced freezing tolerance in
      spinach may be mediated by NO and H2O2 signaling.

PMID- 29061526
TI  - Men with high serotonin 1B receptor binding respond to provocations with
      heightened amygdala reactivity.
AB  - Serotonin signalling influences amygdala reactivity to threat-related emotional
      facial expressions in healthy adults, but in vivo serotonin signalling has never
      been investigated in the context of provocative stimuli in aggressive
      individuals. The aim of this study was to evaluate associations between serotonin
      1B receptor (5-HT1BR) levels and brain reactivity to provocations. We quantified
      regional 5-HT1BR binding using [11C]AZ10419369 positron emission tomography (PET)
      and measured brain activation following provocations with functional magnetic
      resonance imaging (fMRI) in eighteen violent offenders and 25 healthy control
      subjects. The point-subtraction aggression paradigm (PSAP) was used in fMRI to
      elicit provocations in terms of monetary subtractions from a fictive opponent. We
      estimated global 5-HT1BR binding using a linear structural equation model, with a
      single latent response variable (LV1B) modelling shared correlation between 5
      HT1BR binding across multiple brain regions (neocortex, anterior and posterior
      cingulate cortex, raphe, amygdala, hippocampus and striatum). We tested whether
      the LV1B was associated with amygdala, striatal and prefrontal reactivity to
      provocations, adjusting for age, injected mass and group. Across participants,
      LV1B was statistically significantly positively associated with amygdala (p =
      0.01) but not with striatal (p = 0.2) or prefrontal reactivity to provocations (p
      = 0.3). These findings provide novel evidence that 5-HT1BR levels are linked to
      amygdala reactivity to provocations in a cohort of men displaying a wide range of
      aggressive behavior. The data suggest that 5-HT1BR represents an intriguing
      target for reducing excessive neural reactivity to provocations and thereby
      putatively violent behavior.

PMID- 29061525
TI  - Characterization of a new, inducible transgenic mouse model with GFP expression
      in melanocytes and their precursors.
AB  - Melanocytes are neural crest-derived cells that are responsible for mammalian
      hair follicle (HF) pigmentation. The Dct-LacZ transgenic mouse is extensively
      used to study melanocyte biology but lacks conditionally-inducible labelling and
      fluorescent labelling, enabling specific, viable isolation of melanocytes using
      fluorescence-activated cell sorting (FACS). Here, we have generated a Tet-off
      bitransgenic mouse model, Dct-H2BGFP, containing Dct-tTA and TRE-H2BGFP
      transgenes. Characterization of Dct-H2BGFP mice confirmed a pattern of Dct-H2BGFP
      expression in melanoblasts, melanocyte stem cells (McSCs), and terminally
      differentiated melanocytes similar to the expression pattern of previously
      published mouse models Dct-LacZ and iDct-GFP. GFP expression is regulated by
      doxycycline. GFP is shown to co-localize with melanocyte label-retaining cells
      (LRCs) identified through BrdU retention. The GFP-expressing cells identified in
      vivo in the bulge and the secondary hair germ of telogen HFs of Dct-H2BGFP mice
      express the melanocyte and melanocyte stem cell markers Dct and Kit. Using Dct
      H2BGFP mice, we separated GFP-expressing cells from the telogen HF based on FACS
      and showed that GFP-expressing cells express high levels of Kit and Dct, and
      lower levels of HF epithelial keratin genes. We also show that GFP-expressing
      cells express high levels of the melanocyte differentiation genes Tyr, Tyrp1, and
      Pmel17, further substantiating their identity within the melanocyte lineage.
      Thus, Dct-H2BGFP mice are not only useful for the in vivo identification of
      melanocytic cells, but also for isolating them viably and studying their
      molecular and biological properties.

PMID- 29061527
TI  - PAM50: Unbiased multimodal template of the brainstem and spinal cord aligned with
      the ICBM152 space.
AB  - Template-based analysis of multi-parametric MRI data of the spinal cord sets the
      foundation for standardization and reproducibility, thereby helping the discovery
      of new biomarkers of spinal-related diseases. While MRI templates of the spinal
      cord have been recently introduced, none of them cover the entire spinal cord. In
      this study, we introduced an unbiased multimodal MRI template of the spinal cord
      and the brainstem, called PAM50, which is anatomically compatible with the
      ICBM152 brain template and uses the same coordinate system. The PAM50 template is
      based on 50 healthy subjects, covers the full spinal cord (C1 to L2 vertebral
      levels) and the brainstem, is available for T1-, T2-and T2*-weighted MRI
      contrasts and includes a probabilistic atlas of the gray matter and white matter
      tracts. Template creation accuracy was assessed by computing the mean and maximum
      distance error between each individual spinal cord centerline and the PAM50
      centerline, after registration to the template. Results showed high accuracy for
      both T1- (mean = 0.37 +/- 0.06 mm; max = 1.39 +/- 0.58 mm) and T2-weighted (mean
      = 0.11 +/- 0.03 mm; max = 0.71 +/- 0.27 mm) contrasts. Additionally, the
      preservation of the spinal cord topology during the template creation process was
      verified by comparing the cross-sectional area (CSA) profile, averaged over all
      subjects, and the CSA profile of the PAM50 template. The fusion of the PAM50 and
      ICBM152 templates will facilitate group and multi-center studies of combined
      brain and spinal cord MRI, and enable the use of existing atlases of the
      brainstem compatible with the ICBM space.

PMID- 29061529
TI  - Automatic and robust noise suppression in EEG and MEG: The SOUND algorithm.
AB  - Electroencephalography (EEG) and magnetoencephalography (MEG) often suffer from
      noise- and artifact-contaminated channels and trials. Conventionally, EEG and MEG
      data are inspected visually and cleaned accordingly, e.g., by identifying and
      rejecting the so-called "bad" channels. This approach has several shortcomings:
      data inspection is laborious, the rejection criteria are subjective, and the
      process does not fully utilize all the information in the collected data. Here,
      we present noise-cleaning methods based on modeling the multi-sensor and multi
      trial data. These approaches offer objective, automatic, and robust removal of
      noise and disturbances by taking into account the sensor- or trial-specific
      signal-to-noise ratios. We introduce a method called the source-estimate
      utilizing noise-discarding algorithm (the SOUND algorithm). SOUND employs
      anatomical information of the head to cross-validate the data between the
      sensors. As a result, we are able to identify and suppress noise and artifacts in
      EEG and MEG. Furthermore, we discuss the theoretical background of SOUND and show
      that it is a special case of the well-known Wiener estimators. We explain how a
      completely data-driven Wiener estimator (DDWiener) can be used when no anatomical
      information is available. DDWiener is easily applicable to any linear
      multivariate problem; as a demonstrative example, we show how DDWiener can be
      utilized when estimating event-related EEG/MEG responses. We validated the
      performance of SOUND with simulations and by applying SOUND to multiple EEG and
      MEG datasets. SOUND considerably improved the data quality, exceeding the
      performance of the widely used channel-rejection and interpolation scheme. SOUND
      also helped in localizing the underlying neural activity by preventing noise from
      contaminating the source estimates. SOUND can be used to detect and reject noise
      in functional brain data, enabling improved identification of active brain areas.

PMID- 29061528
TI  - Anterior insular thickness predicts speech sound learning ability in bilinguals.
AB  - A previous fMRI study of novel speech sound learning, tied to the methods and
      results presented here, identified groups of advanced and novice learners and
      related their classification to neural activity. To complement those results and
      better elucidate the role of the entire neural system in speech learning, the
      current study analyzed the neuroanatomical data with the goals of 1) uncovering
      the regions of interest (ROIs) that predicted speech learning performance in a
      sample of monolingual and bilingual adults, and 2) examining if the relationship
      between cortical thickness from selected ROIs and individual learning ability
      depends on language group. The ROIs selected were brain regions well-established
      in the literature as areas associated with language and speech processing (i.e.,
      Transverse Superior Temporal Gyrus, anterior insula and posterior insula, all
      bilaterally). High-resolution brain scans (T1-weighted) were acquired from 23
      Spanish-English bilinguals and 20 English monolingual adults. The thickness of
      the left anterior insula significantly predicted speech sound learning ability in
      bilinguals but not monolinguals. These results suggest that aptitude for learning
      a new language is associated with variations in the cortical thickness of the
      left anterior insula in bilinguals. These findings may provide insight into the
      higher order mechanisms involved in speech perception and advance our
      understanding of the unique strategies employed by the bilingual brain during
      language learning.

PMID- 29061530
TI  - Therapeutic potential of Mediator complex subunits in metabolic diseases.
AB  - The multisubunit Mediator is an evolutionary conserved transcriptional
      coregulatory complex in eukaryotes. It is needed for the transcriptional
      regulation of gene expression in general as well as in a gene specific manner.
      Mediator complex subunits interact with different transcription factors as well
      as components of RNA Pol II transcription initiation complex and in doing so act
      as a bridge between gene specific transcription factors and general Pol II
      transcription machinery. Specific interaction of various Mediator subunits with
      nuclear receptors (NRs) and other transcription factors involved in metabolism
      has been reported in different studies. Evidences indicate that ligand-activated
      NRs recruit Mediator complex for RNA Pol II-dependent gene transcription. These
      NRs have been explored as therapeutic targets in different metabolic diseases;
      however, they show side-effects as targets due to their overlapping involvement
      in different signaling pathways. Here we discuss the interaction of various
      Mediator subunits with transcription factors involved in metabolism and whether
      specific interaction of these transcription factors with Mediator subunits could
      be potentially utilized as therapeutic strategy in a variety of metabolic
      diseases.

PMID- 29061531
TI  - Outcomes of Unrelated Donor Stem Cell Transplantion with Post-Transplant
      Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients with
      Severe Sickle Cell Disease.
AB  - Unrelated donor (URD) hematopoietic cell transplantation (HCT) in children with
      sickle cell disease (SCD) is associated with a high incidence of rejection and
      graft-versus-host disease (GVHD). We report on the first 4 patients with severe
      SCD who underwent URD HCT using a novel myeloablative and immunosuppressive
      regimen composed of busulfan, fludarabine, and antithymocyte globulin with a
      single dose of post-transplant cyclophosphamide along with tacrolimus and
      mycophenolate mofetil for GVHD prophylaxis. Three patients engrafted and remain
      disease-free after a median follow-up period of 2.5 years. One patient had
      primary graft failure attributed to low stem cell content of the graft. Of
      interest, none of the engrafted patients developed acute or chronic GVHD. This
      preparative regimen along with the use of post-transplant cyclophosphamide offers
      a promising approach for unrelated donor transplants in patients with SCD and
      needs further corroboration in larger number of patients.

PMID- 29061532
TI  - Fluid: Too Much or Too Little-Transplant Mortality May Hang in the Balance.

PMID- 29061533
TI  - Homeostatic gammadelta T Cell Contents Are Preserved by Granulocyte Colony
      Stimulating Factor Priming and Correlate with the Early Recovery of gammadelta T
      Cell Subsets after Haploidentical Hematopoietic Stem Cell Transplantation.
AB  - Emerging evidence from graft manipulations and immunotherapeutic treatments has
      highlighted a favorable effect of gammadelta T cells in the setting of allogeneic
      hematopoietic stem cell transplantation (alloHSCT). However, gammadelta T cell
      subsets and their distinct features in the allograft have not been characterized.
      Additionally, whether homeostatic gammadelta T cell fractions are influenced by
      treatment with granulocyte colony-stimulating factor (G-CSF) remains elusive. We
      initially compared the phenotypes of gammadelta T cell subsets, including CD27+,
      CD27-, Vdelta1+, Vdelta2+, Vdelta1+CD27+, Vdelta1+CD27-, Vdelta2+CD27+, and
      Vdelta2+CD27- cells, in the peripheral blood of 20 healthy donors before and
      after G-CSF mobilization. The effects of G-CSF on the cytokine production
      capacities of gammadelta T cell subsets were also detected. Moreover, the
      correlation between donor homeostatic gammadelta T cell content and the early
      recoveries of gammadelta T cell subgroups after haploidentical HSCT was
      investigated in 40 pairs of donors and recipients. We found that both the
      proportions and IFN-gamma secretion capacities of peripheral gammadelta T cell
      subsets were preserved in G-CSF-primed grafts. Homeostatic Vdelta1 and Vdelta2
      proportions of donors significantly correlated with the early recoveries of
      Vdelta1 and Vdelta2 cells after haploidentical HSCT. Interestingly, a higher day
      30 Vdelta1 concentration was associated with a lower incidence of cytomegalovirus
      reactivation in recipients. These results not only clarify the preservation of
      gammadelta T cell phenotypes and functional features by G-CSF mobilization but
      also suggest the importance of homeostatic gammadelta T cell content for immune
      recovery after alloHSCT.

PMID- 29061534
TI  - Granulocyte Colony-Stimulating Factor Use after Autologous Peripheral Blood Stem
      Cell Transplantation: Comparison of Two Practices.
AB  - Administration of granulocyte colony-stimulating factor (G-CSF) after autologous
      peripheral blood stem cell transplantation (PBSCT) is generally recommended to
      reduce the duration of severe neutropenia; however, data regarding the optimal
      timing of G-CSFs post-transplantation are limited and conflicting. This
      retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical
      Center between November 5, 2013, and August 9, 2016, of adult inpatient
      autologous PBSCT recipients who received G-CSF empirically starting on day +5
      (early) versus on those who received G-CSF on day +12 only if absolute neutrophil
      count (ANC) was <0.5 * 109/L (ANC-driven). G-CSF was dosed at 300 ug in patients
      weighing <75 kg and 480 ug in those weighing >=75 kg. One hundred consecutive
      patients underwent autologous PBSCT using either the early (n = 50) or ANC-driven
      (n = 50) G-CSF regimen. Patient and transplantation characteristics were
      comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF
      on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or
      at the physician's discretion, 6% (n = 3) started after day +12 at the
      physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median
      start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in
      the early group (P < .0001). For the primary outcome, the median time to
      neutrophil engraftment was 12 days (interquartile range [IQR] 11-13 days) in the
      early group versus 13 days (IQR, 12-14 days) in the ANC-driven group (P = .07).
      There were no significant between-group differences in time to platelet
      engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of
      febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group
      (P = .04); however, there was no significant between-group difference in the
      incidence of positive bacterial cultures or transfer to the intensive care unit.
      The duration of G-CSF administration until neutrophil engraftment was 6 days in
      the early group versus 3 days in the ANC-driven group (P < .0001). The median
      duration of post-transplantation hospitalization was 15 days (IQR, 14-19 days) in
      the early group versus 16 days (IQR, 15-22 days) in the ANC-driven group (P =
      .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven
      initiation of G-CSF following autologous PBSCT were associated with a similar
      time to neutrophil engraftment, length of stay post-transplantation, and 1-year
      overall survival.

PMID- 29061535
TI  - Pharmacodynamic Monitoring Predicts Outcomes of CCR5 Blockade as Graft-versus
      Host Disease Prophylaxis.
AB  - Blocking lymphocyte trafficking after allogeneic hematopoietic stem cell
      transplantation is a promising strategy to prevent graft-versus-host disease
      (GVHD) while preserving the graft-versus-tumor response. Maraviroc, a CCR5
      antagonist, has shown promise in clinical trials, presumably by disrupting the
      migration of effector cells to GVHD target organs. We describe a phosphoflow
      assay to quantify CCR5 blockade during treatment with maraviroc and used it to
      evaluate 28 patients in a phase II study. We found that insufficient blockade of
      CCR5 was associated with significantly worse overall survival (HR, 10.6; 95% CI,
      2.2 to 52.0; P = .004) and higher rates of nonrelapse mortality (HR, 146; 95% CI,
      1.0 to 20,600; P = .04) and severe acute GVHD (HR, 12; 95% CI, 1.9 to 76.6; P =
      .009). In addition, we found that pretransplant high surface expression of CCR5
      on recipient T cells predicted higher nonrelapse mortality and worse GVHD- and
      relapse-free survival. Our results demonstrate that pharmacodynamic monitoring of
      CCR5 blockade unravels interpatient variability in the response to therapy and
      may serve as a clinically informative biomarker.

PMID- 29061536
TI  - Total Body Irradiation Is Safe and Similarly Effective as Chemotherapy-Only
      Conditioning in Autologous Stem Cell Transplantation for Mantle Cell Lymphoma.
AB  - Autologous stem cell transplant (ASCT) consolidation has become a standard
      approach for patients with mantle cell lymphoma (MCL), yet there is little
      consensus on the role of total body irradiation (TBI) as part of high-dose
      transplantation conditioning. We analyzed 75 consecutive patients with MCL who
      underwent ASCT at our institution between 2001 and 2011 with either TBI-based (n
      = 43) or carmustine, etoposide, cytarabine, melphalan (BEAM; n = 32) high-dose
      conditioning. Most patients (97%) had chemosensitive disease and underwent
      transplantation in first remission (89%). On univariate analysis, TBI
      conditioning was associated with a trend toward improved PFS (hazard ratio [HR],
      .53; 95% confidence interval [CI], .28-1.00; P = .052) and similar OS (HR, .59;
      95% CI, .26-1.35; P = .21), with a median follow-up of 6.3 years in the TBI group
      and 6.6 years in the BEAM group. The 5-year PFS was 66% in the TBI group versus
      52% in the BEAM group; OS was 82% versus 68%, respectively. However, on
      multivariate analysis, TBI-based conditioning was not significantly associated
      with PFS (HR, .57; 95% CI .24-1.34; P = .20), after controlling for age, disease
      status at ASCT, and receipt of post-transplantation rituximab maintenance.
      Likewise, early toxicity, nonrelapse mortality, and secondary malignancies were
      similar in the 2 groups. Our data suggest that both TBI and BEAM-based
      conditioning regimens remain viable conditioning options for patients with MCL
      undergoing ASCT.

PMID- 29061537
TI  - Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass
      Index in Children: A Population Based Study.
AB  - PURPOSE: Epidemiological studies demonstrate an association of increased body
      mass index and risk of kidney stone formation in adults. We conducted a
      population based pediatric study to examine the epidemiology of nephrolithiasis
      in Israeli children during a 30-year period, and to determine body mass index
      distribution during the same period. MATERIALS AND METHODS: We accessed data from
      the compulsory medical evaluations of 17-year-old military service candidates in
      Israel before their enlistment during 1980 to 2013. Candidates for the army with
      a history of stone disease were compared to those without such a history.
      RESULTS: Of 1,908,893 candidates 1,691 reported a history of nephrolithiasis,
      yielding an average prevalence rate of 88.6 per 100,000. During 1980 to 1995 the
      average reported prevalence of nephrolithiasis was 69 cases per 100,000. From
      1995 onward the reported prevalence increased by an average of 6% yearly,
      reaching 120 per 100,000 during 2010 to 2012. This increased prevalence was
      observed for males and females but was more prominent among males. Mean +/- SD
      body mass index of stone formers was higher than that of controls (22.7 +/- 3.5
      vs 22.1 +/- 3.9 kg/m2, p <0.001). The trend of increasing body mass index among
      male candidates during 1995 to 2012 parallels the trend of increasing
      nephrolithiasis during these years. The odds ratio for nephrolithiasis in
      candidates with body mass index 30 or greater kg/m2 was 1.7 (range 1.4 to 2.1)
      compared to candidates with a body mass index of 18.5 to 24.9 kg/m2. CONCLUSIONS:
      This large, population based study documents an increasing prevalence of
      nephrolithiasis in children. The possible association of this finding with the
      increase in body mass index during the same period warrants further
      investigation.

PMID- 29061539
TI  - Impact of Adjuvant Urinary Diversion versus Valve Ablation Alone on Progression
      from Chronic to End Stage Renal Disease in Posterior Urethral Valves: A Single
      Institution 15-Year Time-to-Event Analysis.
AB  - PURPOSE: Long-term progression to end stage renal disease of valve ablation alone
      vs ablation followed by additional urinary diversion were compared among children
      with stage 3 chronic kidney disease due to posterior urethral valves. MATERIALS
      AND METHODS: We performed a retrospective study of children with posterior
      urethral valves and stage 3 chronic kidney disease treated at a single
      institution between 1986 and 2011. The 3 treatment groups were classified as
      group 1-valve ablation alone, group 2-ablation plus subsequent vesicostomy and
      group 3-ablation followed by ureterostomies and/or pyelostomies. Baseline
      demographic characteristics were analyzed. Statistical analyses compared the
      incidence of time to end stage renal disease among the intervention groups using
      the Fisher-Freeman-Halton exact test and Kaplan-Meier analysis with the log rank
      test. Cox regression was used to determine predictors of end stage renal disease
      progression. RESULTS: A total of 40 eligible patients were included in the study
      (group 1-14 patients, group 2-13 patients, group 3-13 patients). Baseline
      characteristics and post-intervention estimated glomerular filtration rate
      revealed no significant between-group differences. A statistically significant
      difference in progression to end stage renal disease was noted within 1 year
      after diagnosis of stage 3 chronic kidney disease among the treatment groups (log
      rank test p=0.02). However, cumulative end stage renal disease incidence at 15
      year followup showed no statistical difference (log rank test p=0.628). Cox
      regression analysis determined that bilateral renal dysplasia (HR 2.76, 95% CI
      1.21-6.30) and estimated glomerular filtration rate 60 ml/minute/1.73 m2 or
      greater after intervention (HR 0.23, 95% CI 0.09-0.61) were predictive of the
      likelihood of progression to end stage renal disease. CONCLUSIONS: Urinary
      diversion following valve ablation in children with stage 3 chronic kidney
      disease associated with posterior urethral valves may temporarily delay
      progression to end stage renal disease. However, no long-term benefit was noted
      from diversion in the ultimate incidence of end stage renal disease, suggesting
      that these interventions should be seen as a temporizing measure. Bilateral renal
      dysplasia and post-intervention estimated glomerular filtration rate are
      independent variables predicting overall chronic kidney disease progression.

PMID- 29061538
TI  - Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder
      Cancer Detection.
AB  - PURPOSE: Despite suboptimal sensitivity urine cytology is often performed as an
      adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a
      noninvasive, fast molecular diagnostic test for bladder cancer detection with
      better sensitivity than urine cytology while maintaining adequate specificity.
      MATERIALS AND METHODS: Urine specimens were collected at 18 multinational sites
      from subjects prior to cystoscopy or tumor resection, and from healthy and other
      control subjects without evidence of bladder cancer. The levels of 10 urinary
      mRNAs were measured in a training cohort of 483 subjects and regression analysis
      was used to identify a 5-mRNA model to predict cancer status. The performance of
      the GeneXpert(r) Bladder Cancer Assay, an assay labeled for investigational use
      only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an
      independent test cohort of 450 participants. RESULTS: In the independent test
      cohort the assay ROC curve AUC was 0.87 (95% CI 0.81-0.92). At an example cutoff
      point of 0.4 overall sensitivity was 73% while specificity was 90% and 77% in the
      hematuria and surveillance patient populations, respectively. CONCLUSIONS: We
      developed a 90-minute, urine based test that is simple to perform for the
      detection of bladder cancer. The test can help guide physician decision making in
      the management of bladder cancer. Additional evaluation in a prospective study is
      needed to establish the clinical usefulness of this assay.

PMID- 29061540
TI  - Use of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in
      the Detection of Clinically Significant Prostate Cancer.
AB  - PURPOSE: Guidelines from the NCCN(r) (National Comprehensive Cancer Network(r))
      advocate digital rectal examination screening only in men with elevated prostate
      specific antigen. We investigated the effect of prostate specific antigen on the
      association of digital rectal examination and clinically significant prostate
      cancer in a large American cohort. MATERIALS AND METHODS: We evaluated the
      records of the 35,350 men who underwent digital rectal examination in the
      screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening
      trial for the development of clinically significant prostate cancer (Gleason 7 or
      greater). Followup was 343,273 person-years. The primary outcome was the rate of
      clinically significant prostate cancer among men with vs without suspicious
      digital rectal examination. We performed competing risks regression to evaluate
      the interaction between time varying suspicious digital rectal examination and
      prostate specific antigen. RESULTS: A total of 1,713 clinically significant
      prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95%
      CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal
      examination. Increases in absolute risk were small and clinically irrelevant for
      normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of
      clinically significant prostate cancer at 10 years), clinically relevant for
      elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and
      modestly clinically relevant for equivocal (2 to 3 ng/ml) prostate specific
      antigen (6.5% vs 3.5%). CONCLUSIONS: Digital rectal examination demonstrated
      prognostic usefulness when prostate specific antigen was greater than 3 ng/ml,
      limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3
      ng/ml. These findings support the restriction of digital rectal examination to
      men with higher prostate specific antigen as a reflex test to improve
      specificity. It should not be used as a primary screening modality to improve
      sensitivity.

PMID- 29061542
TI  - A Call for a Shift in Theory and Terminology for Validation Studies in Urological
      Education.

PMID- 29061541
TI  - Personalized Intervention in Monogenic Stone Formers.
AB  - PURPOSE: Treatment of a first-time renal stone consists of acute management
      followed by medical efforts to prevent stone recurrence. Although nephrolithiasis
      is roughly 50% heritable, the presence of a family history usually does not
      affect treatment since most stone disease is regarded as polygenic, ie not
      attributable to a single gene. Recent evidence has suggested that single
      mutations could be responsible for a larger proportion of renal stones than
      previously thought. This intriguing possibility holds the potential to change the
      management paradigm in stone prevention from metabolically directed therapy to
      more specific approaches informed by genetic screening and testing. This review
      synthesizes new findings concerning monogenic kidney stone disease, and provides
      a concise and clinically useful reference for monogenic causes. It is expected
      that increased awareness of these etiologies will lead to increased use of
      genetic testing in recurrent stone formers and further research into the
      prevalence of monogenic stone disease. MATERIALS AND METHODS: We assembled a
      complete list of genes known to cause or influence nephrolithiasis based on
      recent reviews and commentaries. We then comprehensively searched PubMed(r) and
      Google ScholarTM for all research on each gene having a pertinent role in
      nephrolithiasis. We determined which genes could be considered monogenic causes
      of nephrolithiasis. One gene, ALPL, was excluded since nephrolithiasis is a
      relatively minor aspect of the disorder associated with the gene
      (hypophosphatasia). We summarized selected studies and assembled clinically
      relevant details. RESULTS: A total of 27 genes were reviewed in terms of recent
      findings, mode of inheritance of stone disease, known or supposed prevalence of
      mutations in the general population of stone patients and specific therapies or
      considerations. CONCLUSIONS: There is a distinct opportunity for increased use of
      genetic testing to improve the lives of pediatric and adult stone patients.
      Several genes first reported in association with rare disease may be loci for
      novel mutations, heterozygous disease and forme frustes as causes of stones in
      the broader population. Cases of idiopathic nephrolithiasis should be considered
      as potentially having a monogenic basis.

PMID- 29061543
TI  - Peroxisome proliferator activated receptor gamma in human placenta may mediate
      the adverse effects of phthalates exposure in pregnancy.
AB  - Peroxisome-proliferator activated receptor gamma (PPARG) in placenta play an
      important role in pregnancy. Our previous study showed that it mediated the
      effects of phthalates on placental mRNA expression of estrogen synthetases in
      rats. To assess the effects of phthalate exposure on PPARG placental expression,
      and the contribution of PPARG to the effects of phthalates in human. 207 healthy
      pregnant women were recruited and their cord blood and placenta were collected
      upon delivery. Three phthalates, estrogens in cord blood and protein expression
      of PPARG in placenta were measured. Linear regression were used to analyze the
      relationship between phthalates exposure, PPARG expression and hormones.
      Phthalate levels in cord blood were positively associated with PPARG protein
      expression in placenta (p<0.05), whereas estrogens in cord blood were negatively
      associated with phthalate levels and PPARG expression (p<0.05). This study shows
      that PPARG in placenta may mediate the adverse effects of phthalates on pregnancy
      in human.

PMID- 29061545
TI  - Erratum: "An Integrated Experimental Design for the Assessment of Multiple
      Toxicological End Points in Rat Bioassays".
AB  - [This corrects the article DOI: 10.1289/EHP419.].

PMID- 29061544
TI  - Folic Acid and ASDs: A Preventive Measure against Potential Effects of Pesticide
      Exposures?

PMID- 29061546
TI  - Prewire channel stent: a novel stent for bifurcation lesions in a pig model.
AB  - AIMS: Avoiding side branch occlusion is challenging when treating bifurcation
      lesions. A newly designed stent system called the prewire channel stent (PWCS)
      with a side channel positioned between the metallic mesh material and the balloon
      is introduced. We aimed to compare the time taken to position the PWCS against
      that for a conventional stent. METHODS AND RESULTS: The PWCS and a conventional
      stent were used in a pig model. The time taken from the starting point with the
      stent outside the body to reaching the bifurcation of the vessel ready for
      further procedures such as balloon dilatation through the stent mesh opening and
      double kissing balloon technique, etc., was compared in the conventional stent
      and PWCS groups. The time taken in the PWCS stent group included the time from
      sending the stent from outside the body to the desired position of the
      bifurcation of the vessels of the heart, releasing the stent and pulling back the
      balloon (SB time). The time taken in the conventional stent included the time
      from sending the stent from outside the body to the desired position of the
      bifurcation of the vessels of the heart, releasing the stent, pulling back the
      balloon (SB time), and wire exchange (WE time). The SB times for the PWCS and the
      conventional stent groups were not different (28.5+/-3.8 vs. 25.25+/-0.75
      seconds, n=4). The PWCS group did not have "wire exchange," and had no WE time,
      which was 28.5+/-5.7 seconds in the conventional stent group. The total time
      spent in the PWCS group was 28.5+/-3.8 seconds, which was shorter than the
      53.75+/-6.2 seconds (n=4, p<0.05) in the conventional stent group. CONCLUSIONS:
      The PWCS makes "wire exchange" in the side branch (SB) unnecessary and it can be
      as easily manipulated as a conventional stent.

PMID- 29061547
TI  - Randomised comparison of JUDkins vs. tiGEr catheter in coronary angiography via
      the right radial artery: the JUDGE study.
AB  - AIMS: The aim of this study was to compare the performance of the Tiger-II with
      Judkins 3.5L/4R catheters in coronary angiography (CAG) via the transradial
      approach (TRA). METHODS AND RESULTS: Consecutive patients undergoing non-urgent
      CAG via the right TRA were randomised to either the Tiger-II (Terumo) or Judkins
      (3.5L/4R; Medtronic) 5 Fr catheters; 320 patients in each group were randomised.
      Catheter or access site change was required in 57 (17.8%) vs. 68 (21.3%) patients
      allocated to the Tiger-II and Judkins group, respectively (p=0.3). The study's
      primary endpoint of contrast volume (ml) used until completion of CAG was lower
      for Tiger-II vs. Judkins group: 66.8 (54.0-82.0) vs. 73.4 (60.0-94.1), p<0.001.
      Angiography, fluoroscopy time (min) and severe spasm rate were also significantly
      lower for Tiger-II vs. Judkins group: 5.52 (4.17-7.32) vs. 6.85 (5.15-9.63),
      p<0.00, 2.01 (1.32-3.13) vs. 2.24 (1.50-3.50), p=0.01 and 6 (2.8%) vs. 39
      (12.2%), p<0.001, respectively. The Tiger-II catheter obtained better
      opacification grade for the right coronary artery (RCA): 4.0 (4.0-4.0) vs. 4.0
      (3.0-4.0), p=0.02, but slightly compromised opacification of the left anterior
      descending (LAD) and left circumflex (LCX) arteries compared with the Judkins
      group: 3.75 (3.0-4.0) vs. 4.0 (3.5-4.0), p<0.001, and 3.78 (3.6-4.0) vs. 4.0 (3.6
      4.0), p<0.001, respectively. CONCLUSIONS: The Tiger-II was found superior to the
      Judkins 3.5L/4R regarding contrast volume use, procedural and fluoroscopy time,
      spasm rate and RCA imaging, and inferior regarding LAD and LCX imaging.

PMID- 29061549
TI  - Intravenous ultrasound-guided balloon pulmonary angioplasty in the treatment of
      totally occluded chronic thromboembolic pulmonary hypertension.

PMID- 29061548
TI  - Acute performance of a novel restorative transcatheter aortic valve: preclinical
      results.
AB  - AIMS: The Xeltis aortic valve leaflets are made from a bioabsorbable
      supramolecular polymer that guides the tissue to restoring itself. It is mounted
      on a self-expanding nitinol frame that includes three feelers and a native
      leaflet clipping mechanism. We sought to investigate the acute valve performance
      in a preclinical setting. METHODS AND RESULTS: In 33 sheep, 26 mm Xeltis aortic
      valves were transapically implanted in a 23 mm native annulus. Aortography
      (analysable, n=28) and echocardiography (analysable, n=20) images were acquired
      immediately after implantation of the Xeltis aortic valve to assess the acute
      device performance. On echocardiography, transvalvular peak pressure gradient
      (PG) was 7.4 (IQR: 6.0-8.9) mmHg, mean PG was 4.0 (IQR: 3.0-5.0) mmHg, and
      effective orifice area was 2.2 (IQR: 1.6-2.5) cm2. Trace (n=6), mild (n=2) and no
      (n=12) transvalvular aortic regurgitation (AR) were seen. Likewise, no
      paravalvular AR was detected in 7 cases, whereas trace, mild and moderate were
      seen in 7, 5 and 1 cases, respectively. On quantitative videodensitometric AR (VD
      AR) assessment, a median value of 6% (IQR: 1-12%) of AR was seen. Three cases had
      a VD-AR superior to 17%, which has a prognostic significance. Out of these three
      cases, two had echocardiographic assessment available, which showed mild and
      moderate paravalvular regurgitation due to inadequate leaflet clipping.
      CONCLUSIONS: In a transapical ovine model, the novel restorative transcatheter
      aortic valve with bioabsorbable leaflets demonstrated good haemodynamic
      performance comparable to commercially available devices. The highly porous
      polymeric leaflets demonstrated good competence immediately after implantation
      with no cases having >mild transvalvular AR.

PMID- 29061550
TI  - Percutaneous coronary intervention for the left main stem and other bifurcation
      lesions: 12th consensus document from the European Bifurcation Club.
AB  - The European Bifurcation Club (EBC) was initiated in 2004 to support a continuous
      overview of the field of coronary artery bifurcation interventions and aims to
      facilitate a scientific discussion and an exchange of ideas on the management of
      bifurcation disease. The EBC hosts an annual, two-day compact meeting, dedicated
      to bifurcations, which brings together physicians, pathologists, engineers,
      biologists, physicists, mathematicians, epidemiologists and statisticians for
      detailed discussions. Every meeting is finalised with a consensus statement that
      reflects the unique opportunity of combining the opinion of interventional
      cardiologists with the opinion of a large variety of other scientists on
      bifurcation management. A series of consensus sessions dedicated to specific
      topics, to strengthen the consensus debates and focus the discussions, was
      introduced at this year's meeting. The sessions comprise an intensive overview of
      the present literature, a pro and con debate and a voting system, to guide the
      consensus-building process. The present document represents the summary of the up
      to-date EBC consensus and recommendations from the 12th annual EBC meeting in
      2016 in Rotterdam.

PMID- 29061551
TI  - An International Study on the Determinants of Poor Sleep Amongst 15,000 Users of
      Connected Devices.
AB  - BACKGROUND: Sleep is a modifiable lifestyle factor that can be a target for
      efficient intervention studies to improve the quality of life and decrease the
      risk or burden of some chronic conditions. Knowing the profiles of individuals
      with poor sleep patterns is therefore a prerequisite. Wearable devices have
      recently opened new areas in medical research as potential efficient tools to
      measure lifestyle factors such as sleep quantity and quality. OBJECTIVES: The
      goal of our research is to identify the determinants of poor sleep based on data
      from a large population of users of connected devices. METHODS: We analyzed data
      from 15,839 individuals (13,658 males and 2181 females) considered highly
      connected customers having purchased and used at least 3 connected devices from
      the consumer electronics company Withings (now Nokia). Total and deep sleep
      durations as well as the ratio of deep/total sleep as a proxy of sleep quality
      were analyzed in association with available data on age, sex, weight, heart rate,
      steps, and diastolic and systolic blood pressures. RESULTS: With respect to the
      deep/total sleep duration ratio used as a proxy of sleep quality, we have
      observed that those at risk of having a poor ratio (<=0.40) were more frequently
      males (odds ratio [OR]female vs male=0.45, 95% CI 0.38-0.54), younger individuals
      (OR>60 years vs 18-30 years=0.47, 95% CI 0.35-0.63), and those with elevated
      heart rate (OR>78 bpm vs <=61 bpm=1.18, 95% CI 1.04-1.34) and high systolic blood
      pressure (OR>133 mm Hg vs <=116 mm Hg=1.22, 95% CI 1.04-1.43). A direct
      association with weight was observed for total sleep duration exclusively.
      CONCLUSIONS: Wearables can provide useful information to target individuals at
      risk of poor sleep. Future alert or mobile phone notification systems based on
      poor sleep determinants measured with wearables could be tested in intervention
      studies to evaluate the benefits.

PMID- 29061552
TI  - Designing a Self-Management App for Young People With Type 1 Diabetes:
      Methodological Challenges, Experiences, and Recommendations.
AB  - BACKGROUND: Young people with type 1 diabetes often struggle to self-manage their
      disease. Mobile health (mHealth) apps show promise in supporting self-management
      of chronic conditions such as type 1 diabetes. Many health care providers become
      involved in app development. Unfortunately, limited information is available to
      guide their selection of appropriate methods, techniques, and tools for a
      participatory design (PD) project in health care. OBJECTIVE: The aim of our study
      was to develop an mHealth app to support young people in self-managing type 1
      diabetes. This paper presents our methodological recommendations based on
      experiences and reflections from a 2-year research study. METHODS: A mixed
      methods design was used to identify user needs before designing the app and
      testing it in a randomized controlled trial. App design was based on qualitative,
      explorative, interventional, and experimental activities within an overall
      iterative PD approach. Several techniques and tools were used, including
      workshops, a mail panel, think-aloud tests, and a feasibility study. RESULTS: The
      final mHealth solution was "Young with Diabetes" (YWD). The iterative PD approach
      supported researchers and designers in understanding the needs of end users (ie,
      young people, parents, and health care providers) and their assessment of YWD, as
      well as how to improve app usability and feasibility. It is critical to include
      all end user groups during all phases of a PD project and to establish a
      multidisciplinary team to provide the wide range of expertise required to build a
      usable and useful mHealth app. CONCLUSIONS: Future research is needed to develop
      and evaluate more efficient PD techniques. Health care providers need guidance on
      what tools and techniques to choose for which subgroups of users and guidance on
      how to introduce an app to colleagues to successfully implement an mHealth app in
      health care organizations. These steps are important for anyone who wants to
      design an mHealth app for any illness.

PMID- 29061553
TI  - Veterans' Preferences for Exchanging Information Using Veterans Affairs Health
      Information Technologies: Focus Group Results and Modeling Simulations.
AB  - BACKGROUND: The Department of Veterans Affairs (VA) has multiple health
      information technology (HIT) resources for veterans to support their health care
      management. These include a patient portal, VetLink Kiosks, mobile apps, and
      telehealth services. The veteran patient population has a variety of needs and
      preferences that can inform current VA HIT redesign efforts to meet consumer
      needs. OBJECTIVE: This study aimed to describe veterans' experiences using the
      current VA HIT and identify their vision for the future of an integrated VA HIT
      system. METHODS: Two rounds of focus group interviews were conducted with a
      single cohort of 47 veterans and one female caregiver recruited from Bedford,
      Massachusetts, and Tampa, Florida. Focus group interviews included simulation
      modeling activities and a self-administered survey. This study also used an
      expert panel group to provide data and input throughout the study process. High
      fidelity, interactive simulations were created and used to facilitate collection
      of qualitative data. The simulations were developed based on system requirements,
      data collected through operational efforts, and participants' reported
      preferences for using VA HIT. Pairwise comparison activities of HIT resources
      were conducted with both focus groups and the expert panel. Rapid iterative
      content analysis was used to analyze qualitative data. Descriptive statistics
      summarized quantitative data. RESULTS: Data themes included (1) current use of VA
      HIT, (2) non-VA HIT use, and (3) preferences for future use of VA HIT. Data
      indicated that, although the Secure Messaging feature was often preferred, a full
      range of HIT options are needed. These data were then used to develop veteran
      driven simulations that illustrate user needs and expectations when using a HIT
      system and services to access VA health care services. CONCLUSIONS: Patient
      participant redesign processes present critical opportunities for creating a
      human-centered design. Veterans value virtual health care options and prefer
      standardized, integrated, and synchronized user-friendly interface designs.

PMID- 29061554
TI  - Stopping Antidepressants and Anxiolytics as Major Concerns Reported in Online
      Health Communities: A Text Mining Approach.
AB  - BACKGROUND: Internet is a particularly dynamic way to quickly capture the
      perceptions of a population in real time. Complementary to traditional face-to
      face communication, online social networks help patients to improve self-esteem
      and self-help. OBJECTIVE: The aim of this study was to use text mining on
      material from an online forum exploring patients' concerns about treatment
      (antidepressants and anxiolytics). METHODS: Concerns about treatment were
      collected from discussion titles in patients' online community related to
      antidepressants and anxiolytics. To examine the content of these titles
      automatically, we used text mining methods, such as word frequency in a document
      term matrix and co-occurrence of words using a network analysis. It was thus
      possible to identify topics discussed on the forum. RESULTS: The forum included
      2415 discussions on antidepressants and anxiolytics over a period of 3 years.
      After a preprocessing step, the text mining algorithm identified the 99 most
      frequently occurring words in titles, among which were escitalopram, withdrawal,
      antidepressant, venlafaxine, paroxetine, and effect. Patients' concerns were
      related to antidepressant withdrawal, the need to share experience about
      symptoms, effects, and questions on weight gain with some drugs. CONCLUSIONS:
      Patients' expression on the Internet is a potential additional resource in
      addressing patients' concerns about treatment. Patient profiles are close to that
      of patients treated in psychiatry.

PMID- 29061555
TI  - Social Media-Promoted Weight Loss Among an Occupational Population: Cohort Study
      Using a WeChat Mobile Phone App-Based Campaign.
AB  - BACKGROUND: Being overweight and obese are major risk factors for noncommunicable
      diseases such as cardiovascular diseases. The prevalence of overweight and
      obesity is high throughout the world and these issues are very serious in the
      Shunyi District in China. As mobile technologies have rapidly developed, mobile
      apps such as WeChat are well accepted and have the potential to improve health
      behaviors. OBJECTIVE: This study aims to evaluate the effectiveness of a mobile
      app (WeChat) as an intervention on weight loss behavior. METHODS: This study was
      conducted among an occupational population from August 2015 to February 2016 in
      the Shunyi District of Beijing. Before the intervention, the Shunyi District
      Government released an official document for weight loss to all 134 government
      agencies and enterprises in Shunyi District. Participants willing to use our
      official WeChat account were enrolled in a WeChat group and received 6 months of
      interventions for weight loss; those who were not willing to use the account were
      in a control group given routine publicity on weight loss. RESULTS: In total,
      15,310 occupational participants including 3467 participants (22.65%) in the
      control group and 11,843 participants (77.35%) in the WeChat group were enrolled.
      Participants in the WeChat group lost more weight (mean 2.09, SD 3.43 kg) than
      people in the control group (mean 1.78, SD 2.96 kg), and the difference in mean
      weight loss between the two groups for males was significant based on the
      stratification of age and educational level. To control for confounding factors
      and to explore the effects of WeChat on weight loss, the propensity score method
      with a multinominal logistic regression was utilized. For males, this showed that
      the WeChat group (with both active and inactive subgroups) had a higher
      probability of maintaining weight, weight loss from 1 to 2 kg, or weight loss
      more than 2 kg than the control group. However, the control group had higher
      probability of weight loss from 0 to 1 kg. Being active in WeChat was likely to
      be associated with weight loss. The more active participants were in the weight
      loss program via WeChat, the more weight they lost. CONCLUSIONS: The weight loss
      intervention campaign based on an official WeChat account focused on an
      occupation-based population in Shunyi District was effective for males. The more
      active male participants were in using WeChat, the more weight they lost. There
      might be no effect or there may even be a negative effect on weight loss for
      females. Future research should focus on how to improve adherence to the WeChat
      weight loss interventions, to improve and refine the WeChat content such as
      developing a variety of materials to attract interest, and to protect personal
      privacy, especially for females.

PMID- 29061556
TI  - Impact of an Electronic Monitoring Intervention to Improve Adherence to Inhaled
      Medication in Patients with Asthma and Chronic Obstructive Pulmonary Disease:
      Study Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Despite progress in pharmacological and non-pharmacological treatment
      in recent years, the burden of disease among patients with asthma and chronic
      obstructive pulmonary disease (COPD) is high and patients are frequently
      hospitalized due to exacerbations. Reasons for uncontrolled diseases are
      manifold, but are often associated with poor inhalation technique and non
      adherence to the prescribed treatment plan. This causes substantial mortality,
      morbidity, and costs to the healthcare system. In this respect, the study of
      causes for non-adherence and the development of measures to increase and maintain
      treatment adherence in chronic diseases is of major clinical importance.
      OBJECTIVE: The primary objective of this study is to investigate the impact of
      using specific, validated electronic devices on adherence to inhaled medication
      in patients with chronic obstructive lung diseases such as asthma and COPD.
      Furthermore, it aims to assess the impact of a reminder and close supervision of
      the course of disease and quality of life. METHODS: In this ongoing prospective,
      single-blind, randomized controlled study, adherence to inhaled medication is
      analyzed over a 6-month period in at least 154 in- and outpatients with asthma or
      COPD who have experienced at least 1 exacerbation during the last year. Adherence
      is measured using electronic data capture devices, which save the date and time
      of each inhalative device actuation and transfer these data daily via a wireless
      connection to a Web-based database. Patients are randomly assigned to either the
      intervention or the control group. The clinical intervention consists of an
      automated and personal reminder. The intervention group receives an audio
      reminder and support calls in case medication has not been taken as prescribed or
      if rescue medication is used more frequently than pre-specified in the study
      protocol. During the study, participants are assessed every 2 months in the form
      of clinical visits. RESULTS: Recruitment started in January 2014. To date, a
      total of 169 patients have been recruited. Follow-up assessments are still
      ongoing. The study will be concluded in the first quarter of 2017. Data analysis
      will take place during 2017. CONCLUSIONS: Few studies have investigated
      medication adherence in patients with chronic obstructive lung diseases. With
      this prospective study design and the use of state-of-the-art devices for
      measuring adherence, we expect scientifically relevant and clinically meaningful
      results that will have a substantial and positive impact on the provision of
      healthcare in chronically ill patients suffering from asthma or COPD. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02386722;
      https://clinicaltrials.gov/ct2/show/NCT02386722 (Archived by WebCite at
      http://www.webcitation.org/6oJq1fel0).

PMID- 29061557
TI  - Examining Factors of Engagement With Digital Interventions for Weight Management:
      Rapid Review.
AB  - BACKGROUND: Digital interventions for weight management provide a unique
      opportunity to target daily lifestyle choices and eating behaviors over a
      sustained period of time. However, recent evidence has demonstrated a lack of
      user engagement with digital health interventions, impacting on the levels of
      intervention effectiveness. Thus, it is critical to identify the factors that may
      facilitate user engagement with digital health interventions to encourage
      behavior change and weight management. OBJECTIVE: The aim of this study was to
      identify and synthesize the available evidence to gain insights about users'
      perspectives on factors that affect engagement with digital interventions for
      weight management. METHODS: A rapid review methodology was adopted. The search
      strategy was executed in the following databases: Web of Science, PsycINFO, and
      PubMed. Studies were eligible for inclusion if they investigated users'
      engagement with a digital weight management intervention and were published from
      2000 onwards. A narrative synthesis of data was performed on all included
      studies. RESULTS: A total of 11 studies were included in the review. The studies
      were qualitative, mixed-methods, or randomized controlled trials. Some of the
      studies explored features influencing engagement when using a Web-based digital
      intervention, others specifically explored engagement when accessing a mobile
      phone app, and some looked at engagement after text message (short message
      service, SMS) reminders. Factors influencing engagement with digital weight
      management interventions were found to be both user-related (eg, perceived health
      benefits) and digital intervention-related (eg, ease of use and the provision of
      personalized information). CONCLUSIONS: The findings highlight the importance of
      incorporating user perspectives during the digital intervention development
      process to encourage engagement. The review contributes to our understanding of
      what facilitates user engagement and points toward a coproduction approach for
      developing digital interventions for weight management. Particularly, it
      highlights the importance of thinking about user-related and digital tool-related
      factors from the very early stages of the intervention development process.

PMID- 29061558
TI  - Commercially Available Smartphone Apps to Support Postoperative Pain Self
      Management: Scoping Review.
AB  - BACKGROUND: Recently, the use of smartphones to deliver health-related content
      has experienced rapid growth, with more than 165,000 mobile health (mHealth) apps
      currently available in the digital marketplace. With 3 out of 4 Canadians
      currently owning a smartphone, mHealth apps offer opportunities to deliver
      accessible health-related knowledge and support. Many individuals experience pain
      after surgery, which can negatively impact their health-related quality of life,
      including sleep, emotional, and social functioning. Smartphone apps that provide
      remote real-time monitoring and symptom management have the potential to improve
      self-management skills in patients experiencing postoperative pain. Increased
      confidence and practice of self-management skills could contribute to decreased
      postoperative pain and reduce risk of developing persistent pain. Published
      reviews of general pain self-management apps demonstrate a lack of evidence-based
      content, theoretical grounding, and health care professional involvement.
      However, no review to date has focused on the app marketplace specific for
      individuals with postoperative pain. OBJECTIVE: The aim of this study was to
      characterize and critically appraise the content and functionality of
      commercially available postoperative pain self-management apps. METHODS: An
      electronic search and extraction was conducted between December 2016 and March
      2017 of the official Canadian app stores for the three major smartphone operating
      systems (iPhone operating system [iOS], Android, and Windows). Stores were
      searched separately using predetermined search terms. Two authors screened apps
      based on information provided in the public app description. Metadata from all
      included apps were abstracted into a standard spreadsheet. Two authors verified
      the data with reference to the apps and downloaded apps themselves. The content
      and functionality of each app as it pertained to postoperative pain self
      management was rated. RESULTS: A total of 10 apps met the inclusion criteria. All
      included apps were designed exclusively for the Android platform. Education was
      the most common self-management feature offered (8/10, 80%), with none of the
      apps offering features related to goal setting or social support. Overall, no
      single app was comprehensive in terms of pain self-management content. Five (50%)
      apps reported the involvement of a health care provider in their development.
      However, not a single app involved end users in their development, and none of
      the apps underwent scientific evaluation. Additionally, none of the apps were
      designed for use in pediatric patients. CONCLUSIONS: Currently available
      postoperative pain apps for patients lack evidence-based content, goal setting,
      and social support functions. There is a need to develop and test comprehensive
      theory-based apps to support patients with pain self-management care following
      surgery.

PMID- 29061559
TI  - A Survey among Breast Cancer Specialists on the Low Uptake of Therapeutic
      Prevention with Tamoxifen or Raloxifene.
AB  - With this survey, we aimed to address the reasons why physicians are reluctant to
      prescribe breast cancer-preventive therapy with the selective estrogen receptor
      modulators (SERM) tamoxifen or raloxifene despite a strong evidence of efficacy.
      A self-administered 5-point Likert questionnaire was given during breast cancer
      meetings in Europe or sent via email to rank the importance of 10 predefined
      reasons for low uptake of SERMs for breast cancer therapeutic prevention.
      Analyses tested the associations between the stated reasons and physician
      characteristics such as gender, age, country of work, and specialty. Of 246
      delivered questionnaires, 27 were incomplete and were excluded from analysis.
      Overall, there was a small variability in response scores, with a tendency for
      physicians to give moderate importance (score = 3) to all 10 statements. However,
      the top five reasons were: the expected greater preventive effectiveness of
      aromatase inhibitors (70.3% with score >3), difficulty applying current risk
      models in clinical practice (69.9%), the lack of clarity on the most appropriate
      physician for prevention advice (68.4%), the lack of reliable short-term
      biomarkers of effectiveness (67.5%), and the lack of commercial interest in
      therapeutic prevention (66.0%). The lack of reliable short-term biomarkers showed
      a tendency to discriminate between medical oncologists and other breast
      specialists (OR = 2.42; 95% CI, 0.93-6.25). This survey highlights the complexity
      of prescribing decisions among physicians in this context. Coupled with the known
      barriers among eligible women, these data may help to identify strategies to
      increase uptake of breast cancer therapeutic prevention. Cancer Prev Res; 11(1);
      38-43. (c)2017 AACR.

PMID- 29061561
TI  - GP who tried to discredit colleague is struck off.

PMID- 29061560
TI  - Bitter Melon Prevents the Development of 4-NQO-Induced Oral Squamous Cell
      Carcinoma in an Immunocompetent Mouse Model by Modulating Immune Signaling.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer
      worldwide, and tobacco is one of the most common factors for HNSCC of the oral
      cavity. We have previously observed that bitter melon (Momordica charantia)
      extract (BME) exerts antiproliferative activity against several cancers including
      HNSCC. In this study, we investigated the preventive role of BME in 4
      nitroquinoline 1-oxide (4-NQO) carcinogen-induced HNSCC. We observed that BME
      feeding significantly reduced the incidence of 4-NQO-induced oral cancer in a
      mouse model. Histologic analysis suggested control 4-NQO-treated mouse tongues
      showed neoplastic changes ranging from moderate dysplasia to invasive squamous
      cell carcinoma, whereas no significant dysplasia was observed in the BME-fed
      mouse tongues. We also examined the global transcriptome changes in normal versus
      carcinogen-induced tongue cancer tissues, and following BME feeding. Gene
      ontology and pathway analyses revealed a signature of biological processes
      including "immune system process" that is significantly dysregulated in 4-NQO
      induced oral cancer. We identified elevated expression of proinflammatory genes,
      s100a9, IL23a, IL1beta and immune checkpoint gene PDCD1/PD1, during oral cancer
      development. Interestingly, BME treatment significantly reduced their expression.
      Enhancement of MMP9 ("ossification" pathway) was noted during carcinogenesis,
      which was reduced in BME-fed mouse tongue tissues. Our study demonstrates the
      preventive effect of BME in 4-NQO-induced carcinogenesis. Identification of
      pathways involved in carcinogen-induced oral cancer provides useful information
      for prevention strategies. Together, our data strongly suggest the potential
      clinical benefits of BME as a chemopreventive agent in the control or delay of
      carcinogen-induced HNSCC development and progression. Cancer Prev Res; 11(4); 191
      202. (c)2017 AACRSee related editorial by Rao, p. 185.

PMID- 29061562
TI  - Margaret McCartney: We must be smarter about recruitment and retention.

PMID- 29061564
TI  - Cardiovascular and All-Cause Mortality Risk Associated With Urinary Excretion of
      8-oxoGuo, a Biomarker for RNA Oxidation, in Patients With Type 2 Diabetes: A
      Prospective Cohort Study.
AB  - OBJECTIVE: Cardiovascular mortality risk remains high among patients with type 2
      diabetes. Oxidative stress indicated by high urinary excretion of the biomarker
      for RNA oxidation, 8-oxo-7,8-dihydroguanosine (8-oxoGuo), is associated with an
      increased risk of death in newly diagnosed and treated patients. We assessed
      whether 8-oxoGuo is associated with specific cardiovascular and all-cause
      mortality risk. RESEARCH DESIGN AND METHODS: Urinary biomarkers for nucleic acid
      oxidation were measured in a cohort of patients with type 2 diabetes aged >=60
      years (n = 1,863), along with biochemical measurements, questionnaire findings,
      and Central Person Registry information to estimate the hazard ratios (HRs) for
      log2-transformed RNA oxidation using Cox regression. RESULTS: During the 5-year
      follow-up, 173 of 1,863 patients had died (9.3%), including 73 patients who died
      of cardiovascular disease (42.2%). Doubling of RNA oxidation was associated with
      an HR of all-cause mortality of 2.10 (95% CI 1.63-2.71; P < 0.001) and an HR of
      cardiovascular death of 1.82 (95% CI 1.20-2.77; P = 0.005) after multiple
      adjustments. The 5-year absolute risks (ARs) of all-cause mortality (AR 13.9 [95%
      CI 10.8-17.0] vs. AR 6.10 [95% CI 4.00-8.30]) and cardiovascular mortality (AR
      5.49 [95% CI 3.44-7.55] vs. AR 3.16 [95% CI 1.59-4.73]) were approximately two
      times higher in the highest quartile of RNA oxidation than in the lowest
      quartile. CONCLUSIONS: We conclude that high RNA oxidation is associated with all
      cause and cardiovascular mortality risk in patients with type 2 diabetes.
      Targeting oxidative stress via interventions with long-term follow-up may reveal
      the predictive potential of the biomarker 8-oxoGuo.

PMID- 29061563
TI  - Rescue of ATXN3 neuronal toxicity in Caenorhabditiselegans by chemical
      modification of endoplasmic reticulum stress.
AB  - Polyglutamine expansion diseases are a group of hereditary neurodegenerative
      disorders that develop when a CAG repeat in the causative genes is unstably
      expanded above a certain threshold. The expansion of trinucleotide CAG repeats
      causes hereditary adult-onset neurodegenerative disorders, such as Huntington's
      disease, dentatorubral-pallidoluysian atrophy, spinobulbar muscular atrophy and
      multiple forms of spinocerebellar ataxia (SCA). The most common dominantly
      inherited SCA is the type 3 (SCA3), also known as Machado-Joseph disease (MJD),
      which is an autosomal dominant, progressive neurological disorder. The gene
      causatively associated with MJD is ATXN3 Recent studies have shown that this gene
      modulates endoplasmic reticulum (ER) stress. We generated transgenic
      Caenorhabditiselegans strains expressing human ATXN3 genes in motoneurons, and
      animals expressing mutant ATXN3-CAG89 alleles showed decreased lifespan, impaired
      movement, and rates of neurodegeneration greater than wild-type ATXN3-CAG10
      controls. We tested three neuroprotective compounds (Methylene Blue, guanabenz
      and salubrinal) believed to modulate ER stress and observed that these molecules
      rescued ATXN3-CAG89 phenotypes. Furthermore, these compounds required specific
      branches of the ER unfolded protein response (UPRER), reduced global ER and
      oxidative stress, and polyglutamine aggregation. We introduce new C. elegans
      models for MJD based on the expression of full-length ATXN3 in a limited number
      of neurons. Using these models, we discovered that chemical modulation of the
      UPRER reduced neurodegeneration and warrants investigation in mammalian models of
      MJD.

PMID- 29061565
TI  - Cardiovascular Health in African Americans: A Scientific Statement From the
      American Heart Association.
AB  - BACKGROUND AND PURPOSE: Population-wide reductions in cardiovascular disease
      incidence and mortality have not been shared equally by African Americans. The
      burden of cardiovascular disease in the African American community remains high
      and is a primary cause of disparities in life expectancy between African
      Americans and whites. The objectives of the present scientific statement are to
      describe cardiovascular health in African Americans and to highlight unique
      considerations for disease prevention and management. METHOD: The primary sources
      of information were identified with PubMed/Medline and online sources from the
      Centers for Disease Control and Prevention. RESULTS: The higher prevalence of
      traditional cardiovascular risk factors (eg, hypertension, diabetes mellitus,
      obesity, and atherosclerotic cardiovascular risk) underlies the relatively
      earlier age of onset of cardiovascular diseases among African Americans.
      Hypertension in particular is highly prevalent among African Americans and
      contributes directly to the notable disparities in stroke, heart failure, and
      peripheral artery disease among African Americans. Despite the availability of
      effective pharmacotherapies and indications for some tailored pharmacotherapies
      for African Americans (eg, heart failure medications), disease management is less
      effective among African Americans, yielding higher mortality. Explanations for
      these persistent disparities in cardiovascular disease are multifactorial and
      span from the individual level to the social environment. CONCLUSIONS: The
      strategies needed to promote equity in the cardiovascular health of African
      Americans require input from a broad set of stakeholders, including clinicians
      and researchers from across multiple disciplines.

PMID- 29061567
TI  - Canadian researchers whose studies questioned vaccine safety face second
      retraction.

PMID- 29061566
TI  - Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the
      Risk of Atrial Fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to
      heart failure, stroke, and death. Enhanced understanding of modifiable risk
      factors may yield opportunities for prevention. The risk of AF is increased in
      subclinical hyperthyroidism, but it is uncertain whether variations in thyroid
      function within the normal range or subclinical hypothyroidism are also
      associated with AF. METHODS: We conducted a systematic review and obtained
      individual participant data from prospective cohort studies that measured thyroid
      function at baseline and assessed incident AF. Studies were identified from
      MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state
      was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and
      subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4)
      levels within reference range. The association of TSH levels in the euthyroid and
      subclinical hypothyroid range with incident AF was examined by using Cox
      proportional hazards models. In euthyroid participants, we additionally examined
      the association between fT4 levels and incident AF. RESULTS: Of 30 085
      participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had
      subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow
      up. TSH at baseline was not significantly associated with incident AF in
      euthyroid participants or those with subclinical hypothyroidism. Higher fT4
      levels at baseline in euthyroid individuals were associated with increased AF
      risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence
      interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4;
      P for trend <=0.001 across quartiles). Estimates did not substantially differ
      after further adjustment for preexisting cardiovascular disease. CONCLUSIONS: In
      euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are
      associated with increased risk of incident AF.

PMID- 29061568
TI  - R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B
      cell lymphoma.
AB  - The benefit of radiotherapy (RT) after chemotherapy in limited-stage diffuse
      large B-cell lymphoma (DLBCL) remains controversial. We conducted a randomized
      trial in patients with nonbulky limited-stage DLBCL to evaluate the benefit of RT
      after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
      (R-CHOP). Patients were stratified according to the modified International
      Prognostic Index, including lactate dehydrogenase, Eastern Cooperative Oncology
      Group performance status, age, and disease stage. The patients received 4 or 6
      consecutive cycles of R-CHOP delivered once every 2 weeks, followed or not by RT
      at 40 Gy delivered 4 weeks after the last R-CHOP cycle. All patients were
      evaluated by fluorodeoxyglucose-positron emission tomography scans performed at
      baseline, after 4 cycles of R-CHOP, and at the end of treatment. The primary
      objective of the trial was event-free survival (EFS) from randomization. The
      trial randomly assigned 165 patients in the R-CHOP arm and 169 in the R-CHOP plus
      RT arm. In an intent-to-treat analysis with a median follow-up of 64 months, 5
      year EFS was not statistically significantly different between the 2 arms, with
      89% +/- 2.9% in the R-CHOP arm vs 92% +/- 2.4% in the R-CHOP plus RT arm (hazard
      ratio, 0.61; 95% confidence interval [CI], 0.3-1.2; P = .18). Overall survival
      was also not different at 92% (95% CI, 89.5%-94.5%) for patients assigned to R
      CHOP alone and 96% (95% CI, 94.3%-97.7%) for those assigned to R-CHOP plus RT (P
      = not significant). R-CHOP alone is not inferior to R-CHOP followed by RT in
      patients with nonbulky limited-stage DLBCL. This trial was registered at
      www.clinicaltrials.gov as #NCT00841945.

PMID- 29061570
TI  - Future trends in the prevalence of severe activity limitations among older adults
      in Europe: a cross-national population study using EU-SILC.
AB  - OBJECTIVE: To project the proportion of population 65+ years with severe long
      term activity limitations from 2017 to 2047. DESIGN: Large population study.
      SETTING: Population living in private households of the European Union (EU) and
      neighbouring countries. PARTICIPANTS: Participants from the EU Statistics on
      Income and Living Conditions aged 55 years and older and living in one of 26 EU
      and neighbouring countries, who answered the health section of the questionnaire.
      OUTCOME MEASURES: Prevalence of severe long-term activity limitations of
      particular subpopulations (ie, 55+, 65+, 75+ and 85+ years) by sex and country.
      RESULTS: We find a huge variation in the prevalence of self-reported severe long
      term limitations across Europe for both sexes. However, in 2017, about 20% of the
      female population aged 65 years and above and about 16% of their male
      counterparts are expected to report severe long-term activity limitations after
      accounting for differences in reporting. Accounting for cultural differences in
      reporting, we expect that European countries will have about 21% (decile 1:
      19.5%; decile 9: 22.9%) of female and about 16.8% (decile 1: 15.4%; decile 9:
      18.1%) of male 65+ years population with severe long-term activity limitations by
      2047. CONCLUSIONS: Overall, despite the expected increase of life expectancy in
      European countries, our results suggest almost constant shares of older adults
      with severe long-term activity limitations within the next 30 years.

PMID- 29061571
TI  - Competitive Sport Participation Among Athletes With Heart Disease: A Call for a
      Paradigm Shift in Decision Making.

PMID- 29061569
TI  - AML-specific cytotoxic antibodies in patients with durable graft-versus-leukemia
      responses.
AB  - Most patients with acute myeloid leukemia (AML) can only be cured when allogeneic
      hematopoietic stem-cell transplantation induces a graft-versus-leukemia immune
      response (GVL). Although the role of T cells and natural killer cells in tumor
      immunology has been established, less is known about the contribution of B cells.
      From B cells of high-risk patients with AML with potent and lasting GVL
      responses, we isolated monoclonal antibodies directed against antigens expressed
      on the cell surface of AML cells but not on normal hematopoietic and
      nonhematopoietic cells. A number of these donor-derived antibodies recognized the
      U5 snRNP200 complex, a component of the spliceosome that in normal cells is found
      in the cell. In AML however, the U5 snRNP200 complex is exposed on the cell
      membrane of leukemic blasts. U5 snRNP200 complex-specific antibodies induced
      death of AML cells in an Fc receptor-dependent way in the absence of cytotoxic
      leukocytes or complement. In an AML mouse model, treatment with U5 snRNP200
      complex-specific antibodies led to significant tumor growth inhibition. Thus,
      donor-derived U5 snRNP200 complex-recognizing AML-specific antibodies may
      contribute to antitumor responses.

PMID- 29061572
TI  - Future Physicians in the Era of Precision Cardiovascular Medicine.

PMID- 29061573
TI  - Divining the Future of Air Pollution in China: Huge Gains in Health Can Be
      Achieved, but Much Work Remains.

PMID- 29061574
TI  - Anatomy and Flow Characteristics of Neosinus: Important Consideration for
      Thrombosis of Transcatheter Aortic Valves.

PMID- 29061575
TI  - High-Resolution Chromatin Mapping in Heart Failure: Some Answers, but More
      Questions.

PMID- 29061577
TI  - ESC Congress 2017 in Barcelona: Where the World of Cardiology Came Together.

PMID- 29061578
TI  - Dextrocardia: Why Significant Left-Axis Deviation?

PMID- 29061579
TI  - Population Burden of Sudden Death Associated With Hypertrophic Cardiomyopathy.

PMID- 29061576
TI  - Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms,
      Clinical Applications, and Summary of Clinical Trials.
AB  - Despite current established therapy, heart failure (HF) remains a leading cause
      of hospitalization and mortality worldwide. Novel therapeutic targets are
      therefore needed to improve the prognosis of patients with HF. The EMPA-REG
      OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2
      Diabetes Mellitus Patients) demonstrated significant reductions in mortality and
      HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and
      cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium
      glucose cotransporter 2 (SGLT2) inhibitor. The CANVAS trial (Canagliflozin
      Cardiovascular Assessment Study) subsequently reported a reduction in 3-point
      major adverse cardiovascular events and HF hospitalization risk. Although SGLT2
      inhibition may have potential application beyond T2D, including HF, the
      mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors
      remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic
      diuresis, leading to plasma volume contraction and reduced preload, and decreases
      in blood pressure, arterial stiffness, and afterload as well, thereby improving
      subendocardial blood flow in patients with HF. SGLT2 inhibition is also
      associated with preservation of renal function. Based on data from mechanistic
      studies and clinical trials, large clinical trials with SGLT2 inhibitors are now
      investigating the potential use of SGLT2 inhibition in patients who have HF with
      and without T2D. Accordingly, in this review, we summarize the key
      pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence that
      support the rationale for the use of SGLT2 inhibitors in patients with HF who
      have T2D. Because these favorable effects presumably occur independent of blood
      glucose lowering, we also explore the potential use of SGLT2 inhibition in
      patients without T2D with HF or at risk of HF, such as in patients with coronary
      artery disease or hypertension. Finally, we provide a detailed overview and
      summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.

PMID- 29061580
TI  - Letter by Koh Regarding Article, "Dipeptidyl Peptidase-4 Induces Aortic Valve
      Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular
      Interstitial Cells".

PMID- 29061581
TI  - Letter by Bellien and Kamel Regarding Article, "Dipeptidyl Peptidase-4 Induces
      Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling
      in Valvular Interstitial Cells".

PMID- 29061582
TI  - Response by Choi et al to Letters Regarding Article, "Dipeptidyl Peptidase-4
      Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1
      Signaling in Valvular Interstitial Cells".

PMID- 29061585
TI  - In This Issue of Diabetes Care.

PMID- 29061583
TI  - Bioengineered NRF2-siRNA Is Effective to Interfere with NRF2 Pathways and Improve
      Chemosensitivity of Human Cancer Cells.
AB  - The nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor
      in the regulation of many oxidative enzymes and efflux transporters critical for
      oxidative stress and cellular defense against xenobiotics. NRF2 is dysregulated
      in patient osteosarcoma (OS) tissues and correlates with therapeutic outcomes.
      Nevertheless, research on the NRF2 regulatory pathways and its potential as a
      therapeutic target is limited to the use of synthetic small interfering RNA
      (siRNA) carrying extensive artificial modifications. Herein, we report successful
      high-level expression of recombinant siRNA against NRF2 in Escherichia coli using
      our newly established noncoding RNA bioengineering technology, which was purified
      to >99% homogeneity using an anion-exchange fast protein liquid chromatography
      method. Bioengineered NRF2-siRNA was able to significantly knock down NRF2 mRNA
      and protein levels in human OS 143B and MG63 cells, and subsequently suppressed
      the expression of NRF2-regulated oxidative enzymes [heme oxygenase-1 and
      NAD(P)H:quinone oxidoreductase 1] and elevated intracellular levels of reactive
      oxygen species. In addition, recombinant NRF2-siRNA was effective to sensitize
      both 143B and MG63 cells to doxorubicin, cisplatin, and sorafenib, which was
      associated with significant downregulation of NRF2-targeted ATP-binding cassette
      (ABC) efflux transporters (ABCC3, ABCC4, and ABCG2). These findings support that
      targeting NRF2 signaling pathways may improve the sensitivity of cancer cells to
      chemotherapy, and bioengineered siRNA molecules should be added to current tools
      for related research.

PMID- 29061584
TI  - Low Cerebral Exposure Cannot Hinder the Neuroprotective Effects of Panax
      Notoginsenosides.
AB  - A bidirectional route of communication between the gastrointestinal tract and the
      central nervous system, termed the "gut-brain axis," is becoming increasingly
      relevant to treatment of cerebral damage. Panax Notoginsenoside extract (PNE) is
      popular for prevention and treatment of cardio-cerebrovascular ischemic diseases
      although plasma and cerebral exposure levels are extremely low. To date, the
      mechanisms underlying the neuroprotective effects of PNE remain largely unknown.
      In the present study, the neuroprotective effects of PNE were systematically
      studied via investigation of the regulation by PNE of the gastrointestinal
      microbial community and gamma aminobutyric acid (GABA) receptors. The results
      demonstrated that pretreatment with PNE exerted a remarkable neuroprotective
      effect on focal cerebral ischemia/reperfusion (I/R) injury in rats, and the
      efficiency was attenuated in germ-free rats. Pretreatment with PNE could
      significantly prevent downregulation of Bifidobacterium longum (B.L) caused by
      I/R surgery, and colonization by B.L could also exert neuroprotective effects.
      More importantly, both PNE and B.L could upregulate the expression of GABA
      receptors in the hippocampus of I/R rats, and coadministration of a GABA-B
      receptor antagonist could significantly attenuate the neuroprotective effects of
      PNE and B.L. The study above suggests that the neuroprotective effects of PNE may
      be largely attributable to its regulation of intestinal flora, and oral treatment
      with B.L was also useful in therapy of ischemia/reperfusion injury (I/R) by
      upregulating GABA-B receptors.

PMID- 29061586
TI  - The Promise and Practice of Genetics on Diabetes Care: The Fog Rises to Reveal a
      Field of Genetic Complexity in HNF1B.

PMID- 29061587
TI  - Prognostic Impact of Diabetes on Long-term Survival Outcomes in Patients With
      Heart Failure: A Meta-analysis.
AB  - OBJECTIVE: Several studies have explored the impact of diabetes on mortality in
      patients with heart failure (HF). However, the extent to which diabetes may
      confer risk of mortality and hospitalization in this patient population remains
      imperfectly known. Here we examine the independent prognostic impact of diabetes
      on the long-term risk of mortality and hospitalization in patients with HF.
      RESEARCH DESIGN AND METHODS: PubMed, Scopus, and Web of Science from January 1990
      to October 2016 were the data sources used. We included large (n >=1,000)
      observational registries and randomized controlled trials with a follow-up
      duration of at least 1 year. Eligible studies were selected according to
      predefined keywords and clinical outcomes. Data from selected studies were
      extracted, and meta-analysis was performed using random-effects modeling.
      RESULTS: A total of 31 registries and 12 clinical trials with 381,725 patients
      with acute and chronic HF and 102,036 all-cause deaths over a median follow-up of
      3 years were included in the final analysis. Diabetes was associated with a
      higher risk of all-cause death (random-effects hazard ratio [HR] 1.28 [95% CI
      1.21, 1.35]), cardiovascular death (1.34 [1.20, 1.49]), hospitalization (1.35
      [1.20, 1.50]), and the combined end point of all-cause death or hospitalization
      (1.41 [1.29, 1.53]). The impact of diabetes on mortality and hospitalization was
      greater in patients with chronic HF than in those with acute HF. Limitations
      included high heterogeneity and varying degrees of confounder adjustment across
      individual studies. CONCLUSIONS: This updated meta-analysis shows that the
      presence of diabetes per se adversely affects long-term survival and risk of
      hospitalization in patients with acute and chronic HF.

PMID- 29061589
TI  - Comment on Lovshin et al. Dipeptidyl Peptidase 4 Inhibition Stimulates Distal
      Tubular Natriuresis and Increases in Circulating SDF-1alpha1-67 in Patients With
      Type 2 Diabetes. Diabetes Care 2017;40:1073-1081.

PMID- 29061590
TI  - Response to Comment on Lovshin et al. Dipeptidyl Peptidase 4 Inhibition
      Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1alpha1-67
      in Patients With Type 2 Diabetes. Diabetes Care 2017;40:1073-1081.

PMID- 29061591
TI  - Comment on Ely et al. A National Effort to Prevent Type 2 Diabetes: Participant
      Level Evaluation of CDC's National Diabetes Prevention Program. Diabetes Care
      2017;40:1331-1341.

PMID- 29061592
TI  - Response to Comment on Ely et al. A National Effort to Prevent Type 2 Diabetes:
      Participant-Level Evaluation of CDC's National Diabetes Prevention Program.
      Diabetes Care 2017;40:1331-1341.

PMID- 29061593
TI  - Comment on Lachin et al. Association of Glycemic Variability in Type 1 Diabetes
      With Progression of Microvascular Outcomes in the Diabetes Control and
      Complications Trial. Diabetes Care 2017;40:777-783.

PMID- 29061594
TI  - Response to Comment on Lachin et al. Association of Glycemic Variability in Type
      1 Diabetes With Progression of Microvascular Outcomes in the Diabetes Control and
      Complications Trial. Diabetes Care 2017;40:777-783.

PMID- 29061595
TI  - Comment on Craig et al. Prevalence of Celiac Disease in 52,721 Youth With Type 1
      Diabetes: International Comparison Across Three Continents. Diabetes Care
      2017;40:1034-1040.

PMID- 29061596
TI  - Response to Comment on Craig et al. Prevalence of Celiac Disease in 52,721 Youth
      With Type 1 Diabetes: International Comparison Across Three Continents. Diabetes
      Care 2017;40:1034-1040.

PMID- 29061597
TI  - High-dose versus low-dose haemofiltration for the treatment of critically ill
      patients with acute kidney injury: an updated systematic review and meta
      analysis.
AB  - OBJECTIVE: The purpose of this study was to perform a systematic review and meta
      analysis to evaluate the effect of high-dose versus low-dose haemofiltration on
      the survival of critically ill patients with acute kidney injury (AKI). We
      hypothesised that high-dose treatments are not associated with a higher risk of
      mortality. DESIGN: Meta-analysis. SETTING: Randomised controlled trials and two
      arm prospective and retrospective studies were included. PARTICIPANTS: Critically
      ill patients with AKI. INTERVENTIONS: Continuous renal replacement therapy.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes: 90-day mortality,
      intensive care unit (ICU) mortality, hospital mortality; secondary outcomes:
      length of ICU and hospital stay. RESULT: Eight studies including 2970 patients
      were included in the analysis. Pooled results showed no significant difference in
      the 90-mortality rate between patients treated with high-dose or low-dose
      haemofiltration (pooled OR=0.90, 95% CI 0.73 to 1.11, p=0.32). Findings were
      similar for ICU (pooled OR=1.12, 95% CI 0.94 to 1.34, p=0.21) and hospital
      mortality (pooled OR=1.03, 95% CI 0.81 to 1.30, p=0.84). Length of ICU and
      hospital stay were similar between high-dose and low-dose groups. Pooled results
      are not overly influenced by any one study, different cut-off points of
      prescribed dose or different cut-off points of delivered dose. Meta-regression
      analysis indicated that the results were not affected by the percentage of
      patients with sepsis or septic shock. CONCLUSION: High-dose and low-dose
      haemofiltration produce similar outcomes with respect to mortality and length of
      ICU and hospital stay in critically ill patients with AKI.This study was not
      registered at the time the data were collected and analysed. It has since been
      registered on 17 February 2017 at http://www.researchregistry.com/, registration
      number: reviewregistry211.

PMID- 29061598
TI  - The effects of a household conditional cash transfer programme on coverage and
      quality of antenatal care: a secondary analysis of Indonesia's pilot programme.
AB  - OBJECTIVE: To analyse the effectiveness of a household conditional cash transfer
      programme (CCT) on antenatal care (ANC) coverage reported by women and ANC
      quality reported by midwives. DESIGN: The CCT was piloted as a cluster randomised
      control trial in 2007. Intent-to-treat parameters were estimated using linear
      regression and logistic regression. SETTING: Secondary analysis of the
      longitudinal CCT impact evaluation survey, conducted in 2007 and 2009. This
      included 6869 pregnancies and 1407 midwives in 180 control subdistricts and 180
      treated subdistricts in Indonesia. OUTCOME MEASURES: ANC component coverage
      index, a composite measure of each ANC service component as self-reported by
      women, and ANC provider quality index, a composite measure of ANC service
      provided as self-reported by midwives. Each index was created by principal
      component analysis (PCA). Specific ANC component items were also assessed.
      RESULTS: The CCT was associated with improved ANC component coverage index by
      0.07 SD (95% CI 0.002 to 0.141). Women were more likely to receive the following
      assessments: weight (OR 1.56 (95% CI 1.25 to 1.95)), height (OR 1.41 (95% CI
      1.247 to 1.947)), blood pressure (OR 1.36 (95% CI 1.045 to 1.761)), fundal height
      measurements (OR 1.65 (95% CI 1.372 to 1.992)), fetal heart beat monitoring (OR
      1.29 (95% CI 1.006 to 1.653)), external pelvic examination (OR 1.28 (95% CI 1.086
      to 1.505)), iron-folic acid pills (OR 1.42 (95% CI 1.081 to 1.859)) and
      information on pregnancy complications (OR 2.09 (95% CI 1.724 to 2.551)). On the
      supply side, the CCT had no significant effect on the ANC provider quality index
      based on reports from midwives. CONCLUSIONS: The CCT programme improved ANC
      coverage for women, but midwives did not improve ANC quality. The results suggest
      that enhanced ANC utilisation may not be sufficient to improve health outcomes,
      and steps to improve ANC quality are essential for programme impact.

PMID- 29061599
TI  - Leisure time physical activity and dementia risk: a dose-response meta-analysis
      of prospective studies.
AB  - BACKGROUND: There is considerable evidence of the favourable role of more
      physical activity (PA) in fighting against dementia. However, the shape of the
      dose-response relationship is still unclear. OBJECTIVE: To quantitatively
      investigate the relationship between dementia and PA. DESIGN: PubMed, EMBASE,
      Ovid and the Cochrane Library were searched for prospective studies published
      from 1 January 1995 to 15 October 2016. Two types of meta-analyses were performed
      with a focus on the dose-response relationship using two stage generalised least
      squares regression. RESULTS: The primary analysis exhibited a dose-response trend
      for all-cause dementia (ACD), Alzheimer's disease (AD) but not for vascular
      dementia (VD). In the dose-response analysis, either ACD (ptrend <0.005; pnon
      linearity=0.87) or AD (p trend <0.005; pnon-linearity=0.10) exhibited a linear
      relationship with leisure time PA (LTPA) over the observed range (0-2000
      kcal/week or 0-45 metabolic equivalent of task hours per week (MET-h/week)).
      Specifically, for every 500 kcal or 10 MET-h increase per week, there was, on
      average, 10% and 13% decrease in the risk of ACD and AD, respectively.
      CONCLUSIONS: We have reported, for the first time, the dose-response relationship
      between LTPA and dementia, further supporting the international PA guideline from
      the standpoint of dementia prevention.

PMID- 29061600
TI  - Global research trends in spinal ultrasound: a systematic bibliometric analysis.
AB  - BACKGROUND: In recent years, there has been increased interest in the use of
      ultrasound technology in the evaluation of spinal and paraspinal regions.
      OBJECTIVE: This study aimed to investigate trends in spinal ultrasound research
      from 1994 to 2015 and compare the contributions of such research from different
      countries and authors. STUDY DESIGN: Bibliometric analysis. SETTING: Publications
      related to spinal ultrasound from 1994 to 2015 were retrieved from the Web of
      Science database. METHODS: Excel 2013, GraphPad Prism 5, and VOSviewer were used
      to summarise bibliometric features, including the number of publications,
      citation frequency, H-index, and country contributions and hotspots (keywords of
      popular scientific fields). RESULTS: A total of 3859 papers were included. The
      global inflection point (the point in time when the publication growth rate moved
      from positive to negative) came in 2010. The United States contributed the
      largest percentage of articles (1041; 26.9%), with the most citations (19 848)
      and the highest H-index (61). The journals Osteoporosis International and Spine
      had the highest publication number. The University of Toronto and the University
      of California, San Francisco were the most contributive institutions. Studies
      could be divided into three clusters: surgery, osteoporosis, and others. The
      keywords 'adolescent idiopathic scoliosis' and 'anaesthesia' were the latest
      hotspots, appearing around 2012. CONCLUSION: Spinal ultrasound literature has
      grown continuously over the last 22 years, with the rate slowing down after 2010.
      The United States was the largest contributor in this field. Recent studies on
      topics related to 'adolescent idiopathic scoliosis' and 'anaesthesia' were
      relatively new and should be closely followed in spinal ultrasound research.

PMID- 29061601
TI  - The prevalence of non-communicable diseases in northwest Ethiopia: survey of
      Dabat Health and Demographic Surveillance System.
AB  - OBJECTIVE: The main objective of this study was to investigate the magnitude and
      associated factors of non-communicable chronic diseases (NCDs) at the Dabat
      Health and Demographic Surveillance System (DHDSS) site in the northwestern part
      of Ethiopia. DESIGN: A population-based cross-sectional study was conducted from
      October to December 2014. SETTING: HDSS site, Ethiopia. PARTICIPANTS: A total
      population of 67 397 living in 16 053 households was included in the study.
      MEASURES: Structured interviewer-administered questionnaire was used to collect
      data. Self-reported morbidity was used to ascertain NCD. A binary logistic
      regression model was employed to identify the determinants of NCDs. RESULT: One
      thousand one hundred sixty (1.7%) (95% CI 1.62 to 1.82) participants were found
      with at least one type of NCD. Heart disease and hypertension which accounted for
      404 (32.2%) and 401 (31.9%), of the burden, respectively, were the most commonly
      reported NCDs, followed by 347 (27.7%) asthma, 62 (4.9%) diabetes mellitus and 40
      (3.2%) cancer cases. Advanced age (>=65 year) (adjusted OR (AOR)=19.6; 95% CI
      5.83 65.70), urban residence (AOR=2.20; 95% CI 1.83 to 2.65), household food
      insecurity (AOR=1.71; 95% CI 1.37 to 2.12) and high income (AOR=1.28; 95% CI 1.02
      to 1.59) were significantly associated with the reported history of NCDs, whereas
      low (AOR=0.36; 95% CI 0.31 to 0.42) and moderate (AOR=0.33; 95% CI 0.22 to 0.48)
      alcohol consumption, farming occupation (AOR=0.72; 95% CI 0.57 to 0.91), and work
      related physical activities (AOR=0.66; 95% CI 0.50 to 0.88) were inversely
      associated with NCDs. CONCLUSION: There is a high burden of NCDs at the Dabat
      HDSS site. Promotion of regular physical exercise and reducing alcohol
      consumption are essential to mitigate the burden of NCDs. In addition, preventive
      interventions of NCDs should be strengthened among urban dwellers, older age
      people and people of higher economic status.

PMID- 29061602
TI  - Cognitive bias modification for social anxiety in adults who stutter: a
      feasibility study of a randomised controlled trial.
AB  - OBJECTIVE: To determine the feasibility and acceptability of a computerised
      treatment for social anxiety disorder for adults who stutter including
      identification of recruitment, retention and completion rates, large cost drivers
      and selection of most appropriate outcome measure(s) to inform the design of a
      future definitive trial. DESIGN: Two-group parallel design (treatment vs
      placebo), double-blinded feasibility study. PARTICIPANTS: 31 adults who stutter.
      INTERVENTION: Attention training via an online probe detection task in which the
      stimuli were images of faces displaying neutral and disgusted expressions. MAIN
      OUTCOME MEASURES: Psychological measures: Structured Clinical Interview Global
      Assessment of Functioning score; Liebowitz Social Anxiety Scale; Social Phobia
      and Anxiety Inventory; State-Trait Anxiety Inventory; Unhelpful Thoughts and
      Beliefs about Stuttering. Speech fluency: percent syllables stuttered. Economic
      evaluation: resource use questionnaire; EuroQol three-dimension
      questionnaire.Acceptability: Likert Scale questionnaire of experience of trial,
      acceptability of the intervention and randomisation procedure. RESULTS:
      Feasibility of recruitment strategy was demonstrated. Participant feedback
      indicated that the intervention and definitive trial, including randomisation,
      would be acceptable to adults who stutter. Of the 31 participants who were
      randomised, 25 provided data at all three data collection points. CONCLUSIONS:
      The feasibility study informed components of the intervention. Modifications to
      the design are needed before a definitive trial can be undertaken. TRIAL
      REGISTRATION NUMBER: I SRCTN55065978; Post-results.

PMID- 29061603
TI  - Implementation and impact of an online tool used in primary care to improve
      access to financial benefits for patients: a study protocol.
AB  - OBJECTIVES: Addressing the social determinants of health has been identified as
      crucial to reducing health inequities. However, few evidence-based interventions
      exist. This study emerges from an ongoing collaboration between physicians,
      researchers and a financial literacy organisation. Our study will answer the
      following: Is an online tool that improves access to financial benefits feasible
      and acceptable? Can such a tool be integrated into clinical workflow? What are
      patient perspectives on the tool and what is the short-term impact on access to
      benefits? METHODS: An advisory group made up of patients living on low incomes
      and representatives from community agencies supports this study. We will recruit
      three primary care sites in Toronto, Ontario and three in Winnipeg, Manitoba that
      serve low-income communities. We will introduce clinicians to screening for
      poverty and how benefits can increase income. Health providers will be encouraged
      to use the tool with any patient seen. The health provider and patient will
      complete the online tool together, generating a tailored list of benefits and
      resources to assist with obtaining these benefits. A brief survey on this
      experience will be administered to patients after they complete the tool, as well
      as a request to contact them in 1 month. Those who agree to be contacted will be
      interviewed on whether the intervention improved access to financial benefits. We
      will also administer an online survey to providers and conduct focus groups at
      each site. ETHICS AND DISSEMINATION: Key ethical concerns include that patients
      may feel discomfort when being asked about their financial situation, may feel
      obliged to complete the tool and may have their expectations falsely raised about
      receiving benefits. Providers will be trained to address each of these concerns.
      We will share our findings with providers and policy-makers interested in
      addressing the social determinants of health within healthcare settings. TRIAL
      REGISTRATION NUMBER: Clinicaltrials.gov: NCT02959866. Registered 7 November 2016.
      Retrospectively registered. Pre-results.

PMID- 29061604
TI  - Effect of levothyroxine on the progression of carotid intima-media thickness in
      subclinical hypothyroidism patients: a meta-analysis.
AB  - BACKGROUND: Subclinical hypothyroidism (SCH) has been associated with increased
      carotid intima-media thickness (C-IMT) in recent studies, but the effects of
      levothyroxine (L-T4) therapy on C-IMT in SCH patients are still controversial.
      AIM: To evaluate the effect of L-T4 therapy on endothelial function as determined
      by C-IMT in patients with SCH. METHODS: BeforeJuly 2016, we searched the PubMed,
      Embase, Cochrane Library and Google Scholar databases, selecting published
      randomised controlled trials (RCTs) and self-controlled trials for the meta
      analysis. RESULTS: Three RCTs with 117 patients were considered appropriate for
      the meta-analysis. The results of the meta-analysis indicated that L-T4
      significantly decreased the development of C-IMT (weighted mean difference (WMD) 
      0.05 mm, 95% CI -0.08 to -0.01 mm; p=0.025). We also analysed nine studies (self
      controlled trials) with 247 patients and extracted the IMT of SCH patients before
      and after L-T4 treatment. After L-T4 therapy, the pooled estimate of the WMD of
      decreased C-IMT was -0.04 mm (95% CI -0.07 to -0.02 mm; p=0.05). Subgroup
      analysis showed that L-T4 therapy was associated with a decrease in C-IMT among
      patients of mixed genders (WMD -0.03 mm, 95% CI -0.06 to -0.01 mm; p=0.145). L-T4
      therapy was associated with a decrease in C-IMT among female patients (WMD -0.07
      mm, 95% CI -0.14 to -0.01; p=0.186). Longer treatment (>6 months) also resulted
      in a significant decrease in C-IMT (WMD -0.05 mm, 95% CI -0.08 to -0.02;
      p=0.335). CONCLUSION: This meta-analysis indicates that L-T4 treatment of SCH
      patients can reduce C-IMT, possibly as a result of the reduction of total
      cholesterol, triglyceride, low density lipoprotein, systolic blood pressure,
      diastolic blood pressure, lipoprotein(a), and flow-mediated dilatation. Decreased
      C-IMT was observed in SCH patients after long-term (>6 months) L-T4 treatment.
      RCTs with larger samples are needed to verify these observations.

PMID- 29061605
TI  - Suitability of current definitions of ambulatory care sensitive conditions for
      research in emergency department patients: a secondary health data analysis.
AB  - OBJECTIVE: The aim of this study was to investigate the suitability of existing
      definitions of ambulatory care sensitive conditions (ACSC) in the setting of an
      emergency department (ED) by assessing ACSC prevalence in patients admitted to
      hospital after their ED stay. The secondary aim was to identify ACSC suitable for
      specific application in the ED setting. DESIGN: Observational clinical study with
      secondary health data. SETTING: Two EDs of the Charite-Universitatsmedizin
      Berlin. PARTICIPANTS: All medical ED patients of the 'The Charite Emergency
      Medicine Study' (CHARITEM) study, who were admitted as inpatients during the 1
      year study period (n=13 536). OUTCOME MEASURES: Prevalence of ACSC. RESULTS:
      Prevalence of ACSC in the study population differed significantly depending on
      the respective ACSC set used. Prevalence ranged between 19.1% (95% CI 18.4% to
      19.8%; n=2586) using the definition by Albrecht et al and 36.6% (95% CI 35.8% to
      37.5%; n=4960) using the definition of Naumann et al. (p<0.001). Overall ACSC
      prevalence (ie, when using all diagnoses used in any of the assessed ACSC
      definitions) was 48.1% (95% CI 47.2% to 48.9%; n=6505). Some frequently observed
      diagnoses such as 'convulsion and epilepsy' (prevalence: 3.4%, 95% CI 3.1% to
      3.7%; n=455), 'diseases of the urinary system' (prevalence: 1.4%; 95% CI 1.2% to
      1.6%; n=191) or 'atrial fibrillation and flutter' (prevalence: 1.0%, 95% CI 0.8%
      to 1.2%, n=134) are not included in all of the current ACSC definitions.
      CONCLUSIONS: The results highlight the need for an optimised, ED-specific ACSC
      definition. Particular ACSC diagnoses (such as 'convulsion and epilepsy' or
      'diseases of the urinary system' and others) seem to be of special relevance in
      an ED population but are not included in all available ACSC definitions. Further
      research towards the development of a suitable and specific ACSC definition for
      research in the ED setting seems warranted. TRIAL REGISTRATION: German Clinical
      Trials Register Deutsches Register fur Klinische Studien: DRKS-ID: DRKS00000261.

PMID- 29061606
TI  - What are the associations between neighbourhood walkability and sedentary time in
      New Zealand adults? The URBAN cross-sectional study.
AB  - OBJECTIVES: We estimated associations between objectively determined
      neighbourhood 'walkability' attributes and accelerometer-derived sedentary time
      (ST) by sex, city or type of day. DESIGN: A cross-sectional study. SETTING: The
      URBAN (Understanding the Relationship between Activity and Neighbourhoods) study
      was conducted in 48 neighbourhoods across four cities in New Zealand (August 2008
      to October 2010). PARTICIPANTS: The response rate was 41% (2029 recruited
      participants/5007 eligible households approached). In total, 1762 participants
      (aged 41.4+/-12.1, mean+/-SD) met the data inclusion criteria and were included
      in analyses. PRIMARY AND SECONDARY OUTCOME MEASURES: The exposure variables were
      geographical information system (GIS) measures of neighbourhood walkability (ie,
      street connectivity, residential density, land-use mix, retail footprint area
      ratio) for street network buffers of 500 m and 1000 m around residential
      addresses. Participants wore an accelerometer for 7 days. The outcome measure was
      average daily minutes of ST. RESULTS: Data were available from 1762 participants
      (aged 41.4+/-12.1 years; 58% women). No significant main effects of GIS-based
      neighbourhood walkability measures were found with ST. Retail footprint area
      ratio was negatively associated with sedentary time in women, significant only
      for 500 m residential buffers. An increase of 1 decile in street connectivity was
      significantly associated with a decrease of over 5 min of ST per day in
      Christchurch residents for both residential buffers. CONCLUSION: Neighbourhoods
      with proximal retail and higher street connectivity seem to be associated with
      less ST. These effects were sex and city specific.

PMID- 29061607
TI  - Prevalence and risk factors of eye diseases in adult patients with obstructive
      sleep apnoea: results from the SLE.E.P.Y cohort study.
AB  - OBJECTIVES: To assess the occurrence of glaucoma, eyelid, corneal and macular
      disorders in a cohort of patients with obstructive sleep apnoea (OSA) diagnosed
      by overnight polysomnography and to investigate into the risk factors for the
      above eye diseases (EDs). DESIGN: Cross-sectional cohort study between 2014 and
      2015. SETTING: Unit of Respiratory Medicine and Eye Clinic of the University of
      Verona. PARTICIPANTS: 431 consecutive patients were considered eligible. Of
      these, 87 declined to participate, 35 were untraceable and 13 were deceased.
      INTERVENTIONS: A complete ophthalmic evaluation of both eyes for each patient.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Best-corrected distance visual acuity,
      intraocular pressure, corneal, macular and optic nerve optical coherence
      tomography, ocular aberrometry, optic nerve laser polarimetry, visual field test,
      and eyelid examination. RESULTS: 296 patients aged 64.5+/-12.8 years, 23% female
      and 77% male, underwent ophthalmic examination. There was 56% (n=166) prevalence
      of eyelid disorders, 27% (n=80) of corneal disorders, 13% (n=39) of macular
      disorders and 11% (n=33) of glaucoma. Advancing age was not associated with the
      severity of OSA, while significant differences were found for gender, body mass
      index, Oxygen Desaturation Index, smoking habit, hypertension and diabetes.
      Severe OSA was significantly associated with glaucoma (OR, 95% CI 1.05 to 5.93,
      p=0.037). CONCLUSIONS: EDs were more prevalent in our patinets with OSA than in
      the general population. Severe Apnoea/Hypopnoea Index level seemed to play a role
      as risk factor only for glaucoma.

PMID- 29061608
TI  - Impact of regional socioeconomic variation on coordination and cost of ambulatory
      care: investigation of claims data from Bavaria, Germany.
AB  - OBJECTIVES: A considerable proportion of regional variation in healthcare use and
      health expenditures is to date still unexplained. The aim was to investigate
      regional differences in the gatekeeping role of general practitioners and to
      identify relevant explanatory variables at patient and district level in Bavaria,
      Germany. DESIGN: Retrospective routine data analysis using claims data held by
      the Bavarian Association of Statutory Health Insurance Physicians. PARTICIPANTS:
      All patients who consulted a specialist in ambulatory practice within the first
      quarter of 2011 (n=3 616 510). OUTCOMES MEASURES: Of primary interest is the
      effect of district-level measures of rurality, physician density and multiple
      deprivation on (1) the proportion of patients with general practitioner (GP)
      coordination of specialist care and (2) the mean amount in Euros claimed by
      specialist physicians. RESULTS: The proportion of patients whose use of
      specialist services was coordinated by a GP was significantly higher in rural
      areas and in highly deprived regions, as compared with urban and less deprived
      regions. The hierarchical models revealed that increasing age and the presence of
      chronic diseases are the strongest predictive factors for coordination by a GP.
      In contrast, the presence of mental illness, an increasing number of medical
      condition categories and living in a city are predictors for specialist use
      without GP coordination. The amount claimed per patient was ?10 to ?20 higher in
      urban districts and in regions with lower deprivation. Hierarchical models
      indicate that this amount is on average higher for patients living in towns and
      lower for patients in regions with high deprivation. CONCLUSION: The present
      study shows that regional deprivation is closely associated with the way in which
      patients access primary and specialist care. This has clear consequences, both
      with respect to the role of the general practitioner and the financial costs of
      care.

PMID- 29061609
TI  - Caregivers' quality of life and psychological health in response to functional,
      cognitive, neuropsychiatric and social deficits of patients with brain tumour:
      protocol for a cross-sectional study.
AB  - INTRODUCTION: Patients with gliomas generally present cognitive, neuropsychiatric
      and functional deficits. Although previous research has shown that their
      caregivers present a poor quality of life and poor mental health, only a few
      studies have tested in a comprehensive way which deficits/preserved abilities of
      patients predominantly impact their caregivers. Furthermore, only a few studies
      have focused on the social impact of gliomas, which may also damage the
      caregivers' quality of life. Therefore, this cross-sectional study aims to
      investigate which patients' impairments are particularly deleterious for the
      caregivers and whether the histological characteristics of the gliomas also
      affect their quality of life. METHODS AND ANALYSIS: In order to examine these
      research questions, this study intends to include 180 patients (60 patients with
      grade II gliomas, 60 patients with grade III gliomas and 60 patients with grade
      IV gliomas), their caregivers and 60 healthy controls. While patients will
      complete a full battery of cognitive, neuropsychiatric, functional and social
      tests, caregivers will complete questionnaires about their quality of life,
      depression, anxiety and burden. Patients' performances and caregivers' reports of
      depression and anxiety will be compared with the scores of healthy controls.
      Eventually, our aim will be to provide specific care support both to reduce
      patients' deficits and alleviate caregivers' difficulties. ETHICS AND
      DISSEMINATION: The study has obtained the approval of the local faculty ethics
      committee ('Comite d'ethique en sciences comportementales'; 2016-5 S41 and 2015-3
      S37). On completion of the study, data will be kept by Lille University for 5
      years before they are destroyed. Study findings will be disseminated through peer
      reviewed journal publications and conference presentations with no reference to a
      specific individual.

PMID- 29061610
TI  - Cross-sectional study of the provision of interventional oncology services in the
      UK.
AB  - OBJECTIVE: To map out the current provision of interventional oncology (IO)
      services in the UK. DESIGN: Cross-sectional multicentre study. SETTING: All
      National Health Service (NHS) trusts in England and Scottish, Welsh and Northern
      Ireland health boards. PARTICIPANTS: Interventional radiology (IR) departments in
      all NHS trusts/health boards in the UK. RESULTS: A total of 179 NHS trusts/health
      boards were contacted. We received a 100% response rate. Only 19 (11%)
      institutions had an IO lead. 144 trusts (80%) provided IO services or had a
      formal pathway of referral in place for patients to a recipient trust. 21 trusts
      (12%) had plans to provide an IO service or formal referral pathway in the next
      12 months only. 14 trusts (8%) did not have a pathway of referral and no plans to
      implement one. 70 trusts (39%) offered supportive and disease-modifying
      procedures. One trust had a formal referral pathway for supportive procedures. 73
      trusts (41%) provided only supportive procedures (diagnostic or therapeutic). Of
      these, 43 (59%) had a referral pathway for disease-modifying IO procedures,
      either from a regional cancer network or through IR networks and 30 trusts (41%)
      did not have a referral pathway for disease-modifying procedures. CONCLUSION: The
      provision of IO services in the UK is promising; however, collaborative networks
      are necessary to ensure disease-modifying IO procedures are made accessible to
      all patients and to facilitate larger registry data for research with
      commissioning of new services.

PMID- 29061611
TI  - Effects of advanced life support versus basic life support on the mortality rates
      of patients with trauma in prehospital settings: a study protocol for a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Advanced life support (ALS) is thought to be associated with
      improved survival in prehospital trauma care when compared with basic life
      support (BLS). However, evidence on the benefits of prehospital ALS for patients
      with trauma is controversial. Therefore, we aim to clarify if ALS improves
      mortality in patients with trauma when compared with BLS by conducting a
      systematic review and meta-analysis of the recent literature. METHODS AND
      ANALYSIS: We will perform searches in PubMed, Embase and the Cochrane Central
      Register of Controlled Trials for published observational studies, controlled
      before-and-after studies, randomised controlled trials and other controlled
      trials conducted in humans and published until March 2017. We will screen search
      results, assess study selection, extract data and assess the risk of bias in
      duplicate; disagreements will be resolved through discussions. Data from
      clinically homogeneous studies will be pooled using a random-effects meta
      analysis, heterogeneity of effects will be assessed using the chi2 test of
      homogeneity, and any observed heterogeneity will be quantified using the I2
      statistic. Last, the Grading of Recommendations Assessment, Development and
      Evaluation approach will be used to rate the quality of the evidence. ETHICS AND
      DISSEMINATION: Our study does not require ethical approval as it is based on
      findings of previously published articles. Results will be disseminated through
      publication in a peer-reviewed journal, presentations at relevant conferences and
      publications for patient information. TRIAL REGISTRATION NUMBER: PROSPERO
      (International Prospective Register of Systematic Reviews) registration number
      CRD42017054389.

PMID- 29061612
TI  - Comparison of regional with general anaesthesia on postoperative delirium (RAGA
      delirium) in the older patients undergoing hip fracture surgery: study protocol
      for a multicentre randomised controlled trial.
AB  - INTRODUCTION: Postoperative delirium (POD) is a common serious postoperative
      complication especially in older people and is associated with increased
      mortality, morbidity and healthcare costs. There is no clear consensus which
      anaesthesia is associated with less incidence of POD for older patients. We aim
      to assess whether regional anaesthesia results in lower incidence of POD
      comparing with general anaesthesia (GA) among older patients undergoing hip
      fracture surgery. METHODS AND ANALYSIS: RAGA-delirium is a pragmatic,
      multicentre, prospective, parallel grouped, randomised controlled clinical trial
      comparing RA or GA for hip fracture surgery. A total of 1000 patients who are 65
      years or over and who are having planned hip fracture surgery in nine clinical
      trial centres of China will be randomised in a 1:1 ratio to receive either
      anaesthesia for the surgery. The primary endpoint will be the incidence of POD at
      day 7. The secondary endpoints will be the subtype, severity and duration of
      delirium, postoperative acute pain score, incidence of other postoperative non
      delirium complications, quality of life and cost-effective outcomes.
      Randomisation will be performed at the patient level using computer-generated
      assignment. Outcome assessors will be blinded from intervention assignment.
      Assessments will be conducted before surgery, intraoperatively, postoperatively,
      during the hospital stay, at 30-day, 6-month and 1-year postoperative intervals.
      POTENTIAL IMPACT OF STUDY: This study will provide clinical evidence with a more
      robust methodology to help anaesthetists in selecting appropriate anaesthesia for
      older patients with high risk for POD. At the era of increasing emphasis on
      delirium prevention, this trial has the potential to inform the future national
      guideline to reduce POD. ETHICS AND DISSEMINATION: Ethical approved by the local
      institutional review board. Trial results will be presented at national and
      international academic conferences, and published in peer-reviewed journals.
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02213380); pre-results.

PMID- 29061613
TI  - Reaching consensus on reporting patient and public involvement (PPI) in research:
      methods and lessons learned from the development of reporting guidelines.
AB  - INTRODUCTION: Patient and public involvement (PPI) is inconsistently reported in
      health and social care research. Improving the quality of how PPI is reported is
      critical in developing a higher quality evidence base to gain a better insight
      into the methods and impact of PPI. This paper describes the methods used to
      develop and gain consensus on guidelines for reporting PPI in research studies
      (updated version of the Guidance for Reporting Patient and Public Involvement
      (GRIPP2)). METHODS: There were three key stages in the development of GRIPP2:
      identification of key items for the guideline from systematic review evidence of
      the impact of PPI on health research and health services, a three-phase online
      Delphi survey with a diverse sample of experts in PPI to gain consensus on
      included items and a face-to-face consensus meeting to finalise and reach
      definitive agreement on GRIPP2. Challenges and lessons learnt during the
      development of the reporting guidelines are reported. DISCUSSION: The process of
      reaching consensus is vital within the development of guidelines and policy
      directions, although debate around how best to reach consensus is still needed.
      This paper discusses the critical stages of consensus development as applied to
      the development of consensus for GRIPP2 and discusses the benefits and challenges
      of consensus development.

PMID- 29061614
TI  - Impact of child summertime obesity interventions on body mass index, and weight
      related behaviours: a systematic review and meta-analysis protocol.
AB  - INTRODUCTION: In previous studies, it has been found that on average, children
      consistently gained weight during the summer months at an increased rate compared
      with the 9-month school year. This contributed to an increased prevalence of
      overweight and obesity in children. Several obesity-related interventions have
      occurred during or targeting the summer months. We propose to conduct a
      systematic review and meta-analysis of the impact of obesity prevention and
      treatment interventions for school-age children conducted during the summer or
      targeting the summer months when children are not in school on their body mass
      index (BMI), or weight-related behaviours. METHODS AND ANALYSES: A literature
      search will be conducted by the first author (JPM) using MEDLINE/PubMed, Cochrane
      Library, Scopus, CINAHL, PsycINFO, EMBASE and Proquest Dissertations and Theses
      databases from the date of inception to present. Studies must examine
      interventions that address the modification or promotion of weight-related
      behaviours (eg, dietary patterns, eating behaviours, physical activity (PA),
      sedentary behaviour or sleep) and target school-age children (ages 5-18). The
      primary outcomes will be changes from baseline to postintervention and/or the
      last available follow-up measurement in weight, BMI, BMI percentile, standardised
      BMI or per cent body fat. Secondary outcomes will include changes in dietary
      intake, PA, sedentary behaviour or sleep. Risk of bias will be assessed using the
      Cochrane risk of bias tool for randomised and non-randomised studies, as
      appropriate. ETHICS AND DISSEMINATION: Because this is a protocol for a
      systematic review, ethics approval will not be required. The findings will be
      disseminated via presentations at scientific conferences and published in a peer
      reviewed journal. All amendments to the protocol will be documented and dated and
      reported in the PROSPERO trial registry. PROSPERO REGISTRATION NUMBER:
      CRD42016041750.

PMID- 29061615
TI  - Elder abuse as a risk factor for psychological distress among older adults in
      India: a cross-sectional study.
AB  - OBJECTIVES: This study examines the association between elder abuse and
      psychological distress among older adults in India and explores whether this
      association varies by the level of psychosocial and material resources. DESIGN:
      The study uses a cross-sectional survey design. SETTING: The data are drawn from
      a representative sample of 9589 adults aged 60 and above in seven Indian states
      Himachal Pradesh, Punjab, West Bengal, Odisha, Maharashtra, Kerala and Tamil Nadu
      in 2011. STATISTICAL ANALYSES: Secondary analysis, using bivariate and
      multivariate logistic regression models, is conducted using the United Nations
      Population Fund project Building Knowledge Base on Ageing in India survey. Elder
      abuse (physical and/or emotional) emanating from family members in the previous
      month before the survey is examined. Multivariate models are run on the total
      analytical sample and for men and women separately. RESULTS: The overall
      prevalence of psychological distress among persons aged 60 and over living in the
      seven Indian States is 40.6%. Among those older persons who experienced some form
      of physical or emotional abuse or violence in the last month, the prevalence of
      psychological distress is much higher than that in the general older population,
      at 61.6% (p<0.001). The results show that the experience of abuse is negatively
      associated with the mental health of older adults, and this relationship persists
      even after controlling for demographic and socioeconomic factors (OR=1.60, 95% CI
      1.22 to 2.09). The findings also suggest that household wealth has an inverse
      relationship with mental health, with the association between experiencing elder
      abuse and reporting poor mental health being strongest among older people in
      wealthy households. CONCLUSIONS: Elder abuse in India is currently a neglected
      phenomenon, and greater recognition of the link between abuse and mental health
      is critical to improve the well-being of vulnerable older adults, some of whom
      may be 'hidden' within well-off households.

PMID- 29061616
TI  - Transforaminal lumbar interbody fusion with cortical bone trajectory screws
      versus traditional pedicle screws fixation: a study protocol of randomised
      controlled trial.
AB  - INTRODUCTION: Transforaminal lumbar interbody fusion (TLIF) has been widely used
      in the treatment of lumbar degenerative disc disorders and shows favourable
      clinical results. Recently, cortical bone trajectory (CBT) has become a new
      trajectory for screw insertion in the lumbar spine. Several biomechanical studies
      have demonstrated that the CBT technique achieves screw purchase and strength
      greater than the traditional method. Currently, the available data on the
      clinical effectiveness of the two performed surgeries, TLIF with CBT screws (CBT
      TLIF) and TLIF with traditional pedicle screws (PS-TLIF), are insufficient. This
      is the first randomised study to compare CBT-TLIF against traditional PS fixation
      and will provide recommendations for treating patients with lumbar degenerative
      disc disorders. METHODS AND ANALYSIS: A blinded randomised controlled trial
      (blinding for the patient and statistician, rather than for the clinician and
      researcher) will be conducted. A total of 254 participants with lumbar disc
      degenerative disease who are candidates for TLIF surgery will be randomly
      allocated to either the CBT-TLIF group or the PS-TLIF group at a ratio of 1:1.
      The primary clinical outcome measures are the incidence of adjacent cranial facet
      joint violation, fusion rate and the screw loosening rate. Secondary clinical
      outcome measures are Visual Analogue Scale (VAS) of back pain, VAS of leg pain,
      Oswestry Disability Index, operative time, intraoperative blood loss and
      complications. These parameters will be evaluated on day 3, and then at 1, 3, 6,
      12 and 24 months postoperatively. ETHICS AND DISSEMINATION: This study has been
      reviewed and approved by the Institutional Review Board of the Second Affiliated
      Hospital and Yuying Children's Hospital of Wenzhou Medical University (batch:
      2017-03). The results will be presented in peer-reviewed journals and an
      international spine-related meeting after completion of the study. TRIAL
      REGISTRATION NUMBER: NCT03105167; Pre-results.

PMID- 29061617
TI  - Secondary analysis of frequency, circumstances and consequences of calculation
      errors of the HEART (history, ECG, age, risk factors and troponin) score at the
      emergency departments of nine hospitals in the Netherlands.
AB  - OBJECTIVE: The HEART score can accurately stratify the risk of major adverse
      cardiac events (MACE) in patients with chest pain. We investigated the frequency,
      circumstances and potential consequences of errors in its calculation. METHODS:
      We performed a secondary analysis of a stepped wedge trial of patients with chest
      pain presenting to nine Dutch emergency departments. We recalculated HEART scores
      for all patients by re-evaluating the elements age (A), risk factors (R) and
      troponin (T) and compared these new scores with those given by physicians in
      daily practice. We investigated which circumstances increased the probability of
      incorrect scoring and explored the potential consequences. RESULTS: The HEART
      score was incorrectly scored in 266 out of 1752 patients (15.2%; 95% CI 13.5% to
      16.9%). Most errors occurred in the R ('Risk factors') element (61%). Time of
      admission, and patient's age or gender did not contribute to errors, but more
      errors were made in patients with higher scores. In 102 patients (5.8%, 95% CI
      4.7% to 6.9%) the incorrect HEART score resulted in incorrect risk categorisation
      (too low or too high). Patients with an incorrectly calculated HEART score had a
      higher risk of MACE (OR 1.85; 95% CI 1.37 to 2.50), which was largely related to
      more errors being made in patients with higher HEART scores. CONCLUSIONS: Our
      results show that the HEART score was incorrectly calculated in 15% of patients,
      leading to inappropriate risk categorisation in 5.8% which may have led to
      suboptimal clinical decision-making and management. Actions should be taken to
      improve the score's use in daily practice.

PMID- 29061618
TI  - Critical Care Cycling Study (CYCLIST) trial protocol: a randomised controlled
      trial of usual care plus additional in-bed cycling sessions versus usual care in
      the critically ill.
AB  - INTRODUCTION: In-bed cycling with patients with critical illness has been shown
      to be safe and feasible, and improves physical function outcomes at hospital
      discharge. The effects of early in-bed cycling on reducing the rate of skeletal
      muscle atrophy, and associations with physical and cognitive function are
      unknown. METHODS AND ANALYSIS: A single-centre randomised controlled trial in a
      mixed medical-surgical intensive care unit (ICU) will be conducted. Adult
      patients (n=68) who are expected to be mechanically ventilated for more than 48
      hours and remain in ICU for a further 48 hours from recruitment will be randomly
      allocated into either (1) a usual care group or (2) a group that receives usual
      care and additional in-bed cycling sessions. The primary outcome is change in
      rectus femoris cross-sectional area at day 10 in comparison to baseline measured
      by blinded assessors. Secondary outcome measures include muscle strength,
      incidence of ICU-acquired weakness, handgrip strength, time to achieve functional
      milestones (sitting out of bed, walking), Functional Status Score in ICU, ICU
      Mobility Scale, 6 min walk test 1 week post-ICU discharge, incidence of delirium
      and quality of life (EuroQol Five Dimensions questionnaire Five Levels scale).
      Quality of life assessments will be conducted post-ICU admission at day 10, 3 and
      6 months after acute hospital discharge. Participants in the intervention group
      will complete an acceptability of intervention questionnaire. ETHICS AND
      DISSEMINATION: Appropriate ethical approval from Metro South Health Human
      Research Ethics Committee has been attained. Results will be published in peer
      reviewed publications and presented at scientific conferences to assist planning
      of future multicentre randomised controlled trials (if indicated) that will test
      in-bed cycling as an intervention to improve the physical, cognitive and health
      related quality of life outcomes of patients with critical illness. TRIAL
      REGISTRATION NUMBER: This trial has been prospectively registered on the
      Australian and New Zealand Clinical Trial Registry (ACTRN12616000948493); Pre
      results.

PMID- 29061619
TI  - A scoping review protocol on the roles and tasks of peer reviewers in the
      manuscript review process in biomedical journals.
AB  - INTRODUCTION: The primary functions of peer reviewers are poorly defined. Thus
      far no body of literature has systematically identified the roles and tasks of
      peer reviewers of biomedical journals. A clear establishment of these can lead to
      improvements in the peer review process. The purpose of this scoping review is to
      determine what is known on the roles and tasks of peer reviewers. METHODS: We
      will use the methodological framework first proposed by Arksey and O'Malley and
      subsequently adapted by Levac et al and the Joanna Briggs Institute. The scoping
      review will include all study designs, as well as editorials, commentaries and
      grey literature. The following eight electronic databases will be searched (from
      inception to May 2017): Cochrane Library, Cumulative Index to Nursing and Allied
      Health Literature, Educational Resources Information Center, EMBASE, MEDLINE,
      PsycINFO, Scopus and Web of Science. Two reviewers will use inclusion and
      exclusion criteria based on the 'Population-Concept-Context' framework to
      independently screen titles and abstracts of articles considered for inclusion.
      Full-text screening of relevant eligible articles will also be carried out by two
      reviewers. The search strategy for grey literature will include searching in
      websites of existing networks, biomedical journal publishers and organisations
      that offer resources for peer reviewers. In addition we will review journal
      guidelines to peer reviewers on how to perform the manuscript review. Journals
      will be selected using the 2016 journal impact factor. We will identify and
      assess the top five, middle five and lowest-ranking five journals across all
      medical specialties. ETHICS AND DISSEMINATION: This scoping review will undertake
      a secondary analysis of data already collected and does not require ethical
      approval. The results will be disseminated through journals and conferences
      targeting stakeholders involved in peer review in biomedical research.

PMID- 29061620
TI  - Identifying and sharing data for secondary data analysis of physical activity,
      sedentary behaviour and their determinants across the life course in Europe:
      general principles and an example from DEDIPAC.
AB  - BACKGROUND: The utilisation of available cross-European data for secondary data
      analyses on physical activity, sedentary behaviours and their underlying
      determinants may benefit from the wide variation that exists across Europe in
      terms of these behaviours and their determinants. Such reuse of existing data for
      further research requires Findable; Accessible; Interoperable; Reusable (FAIR)
      data management and stewardship. We here describe the inventory and development
      of a comprehensive European dataset compendium and the process towards cross
      European secondary data analyses of pooled data on physical activity, sedentary
      behaviour and their correlates across the life course. METHODS: A five-step
      methodology was followed by the European Determinants of Diet and Physical
      Activity (DEDIPAC) Knowledge Hub, covering the (1) identification of relevant
      datasets across Europe, (2) development of a compendium including details on the
      design, study population, measures and level of accessibility of data from each
      study, (3) definition of key topics and approaches for secondary analyses, (4)
      process of gaining access to datasets and (5) pooling and harmonisation of the
      data and the development of a data harmonisation platform. RESULTS: A total of
      114 unique datasets were found for inclusion within the DEDIPAC compendium. Of
      these datasets, 14 were eventually obtained and reused to address 10 exemplar
      research questions. The DEDIPAC data harmonisation platform proved to be useful
      for pooling, but in general, harmonisation was often restricted to just a few
      core (crude) outcome variables and some individual-level sociodemographic
      correlates of these behaviours. CONCLUSIONS: Obtaining, pooling and harmonising
      data for secondary data analyses proved to be difficult and sometimes even
      impossible. Compliance to FAIR data management and stewardship principles
      currently appears to be limited for research in the field of physical activity
      and sedentary behaviour. We discuss some of the reasons why this might be the
      case and present recommendations based on our experience.

PMID- 29061621
TI  - Detection and management of familial hypercholesterolaemia in primary care in
      Australia: protocol for a pragmatic cluster intervention study with pre-post
      intervention comparisons.
AB  - INTRODUCTION: Familial hypercholesterolaemia (FH), an autosomal dominant disorder
      of lipid metabolism, results in accelerated onset of atherosclerosis if left
      untreated. Lifelong treatment with diet, lifestyle modifications and statins
      enable a normal lifespan for most patients. Early diagnosis is critical. This
      protocol trials a primary care-based model of care (MoC) to improve detection and
      management of FH. METHODS AND ANALYSIS: Pragmatic cluster intervention study with
      pre-post intervention comparisons in Australian general practices. At study
      baseline, current FH detection practice is assessed. Medical records over 2 years
      are electronically scanned using a data extraction tool (TARB-Ex) to identify
      patients at increased risk. High-risk patients are clinically reviewed to provide
      definitive, phenotypic diagnosis using Dutch Lipid Clinic Network Criteria. Once
      an index family member with FH is identified, the primary care team undertake
      cascade testing of first-degree relatives to identify other patients with FH.
      Management guidance based on disease complexity is provided to the primary care
      team. Study follow-up to 12 months with TARB-Ex rerun to identify total number of
      new FH cases diagnosed over study period (via TARB-Ex, cascade testing and new
      cases presenting). At study conclusion, patient and clinical staff perceptions of
      enablers/barriers and suggested improvements to the approach will be examined.
      Resources at each stage will be traced to determine the economic implications of
      implementing the MoC and costed from health system perspective. Primary outcomes:
      increase in number of index cases clinically identified; reduction in low-density
      lipoprotein cholesterol of treated cases. SECONDARY OUTCOMES: increase in the
      number of family cases detected/contacted; cost implications of the MoC. ETHICS
      AND DISSEMINATION: Study approval by The University of Notre Dame Australia Human
      Research Ethics Committee Protocol ID: 0 16 067F. Registration: Australian New
      Zealand Clinical Trials Registry ID: 12616000630415. Information will be
      disseminated via research seminars, conference presentations, journal articles,
      media releases and community forums. TRIAL REGISTRATION NUMBER: Australian New
      Zealand Clinical Trials Registry ID 12616000630415; Pre-results.

PMID- 29061622
TI  - Factors associated with patient activation in an Australian population with
      comorbid diabetes and chronic kidney disease: a cross-sectional study.
AB  - OBJECTIVE: To evaluate the extent of patient activation and factors associated
      with activation in adults with comorbid diabetes and chronic kidney disease
      (CKD). DESIGN: A cross-sectional study. SETTING: Renal/diabetes clinics of four
      tertiary hospitals across the two largest states of Australia. STUDY POPULATION:
      Adult patients (over 18 years) with comorbid diabetes and CKD (estimated
      glomerular filtration rate <60 mL/min/1.73 m2). MAIN OUTCOME MEASURES: Patients
      completed the Patient Activation Measure, the Kidney Disease Quality of Life and
      demographic and clinical data survey from January to December 2014. Factors
      associated with patient activation were examined using chi2 or t-tests and linear
      regression. RESULTS: Three hundred and five patients with median age of 68 (IQR
      14.8) years were studied. They were evenly distributed across socioeconomic
      groups, stage of kidney disease and duration of diabetes but not gender.
      Approximately 46% reported low activation. In patients with low activation, the
      symptom/problem list, burden of kidney disease subscale and mental composite
      subscale scores were all significantly lower (all p<0.05). On multivariable
      analysis, factors associated with lower activation for all patients were older
      age, worse self-reported health in the burden of kidney disease subscale and
      lower self-care scores. Additionally, in men, worse self-reported health in the
      mental composite subscale was associated with lower activation and in women,
      worse self-reported health scores in the symptom problem list and greater renal
      impairment were associated with lower activation. CONCLUSION: Findings from this
      study suggest that levels of activation are low in patients with diabetes and
      CKD. Older age and worse self-reported health were associated with lower
      activation. This data may serve as the basis for the development of interventions
      needed to enhance activation and outcomes for patients with diabetes and CKD.

PMID- 29061623
TI  - Key factors of case management interventions for frequent users of healthcare
      services: a thematic analysis review.
AB  - OBJECTIVE: The aim of this paper was to identify the key factors of case
      management (CM) interventions among frequent users of healthcare services found
      in empirical studies of effectiveness. DESIGN: Thematic analysis review of CM
      studies. METHODS: We built on a previously published review that aimed to report
      the effectiveness of CM interventions for frequent users of healthcare services,
      using the Medline, Scopus and CINAHL databases covering the January 2004-December
      2015 period, then updated to July 2017, with the keywords 'CM' and 'frequent
      use'. We extracted factors of successful (n=7) and unsuccessful (n=6) CM
      interventions and conducted a mixed thematic analysis to synthesise findings.
      Chaudoir's implementation of health innovations framework was used to organise
      results into four broad levels of factors: (1) ,environmental/organisational
      level, (2) practitioner level, (3) patient level and (4) programme level.
      RESULTS: Access to, and close partnerships with, healthcare providers and
      community services resources were key factors of successful CM interventions that
      should target patients with the greatest needs and promote frequent contacts with
      the healthcare team. The selection and training of the case manager was also an
      important factor to foster patient engagement in CM. Coordination of care, self
      management support and assistance with care navigation were key CM activities.
      The main issues reported by unsuccessful CM interventions were problems with case
      finding or lack of care integration. CONCLUSIONS: CM interventions for frequent
      users of healthcare services should ensure adequate case finding processes,
      rigorous selection and training of the case manager, sufficient intensity of the
      intervention, as well as good care integration among all partners. Other studies
      could further evaluate the influence of contextual factors on intervention
      impacts.

PMID- 29061625
TI  - Observational study of factors associated with return of home sampling kits for
      sexually transmitted infections requested online in the UK.
AB  - OBJECTIVES: To investigate factors associated with the return of home sampling
      kits for sexually transmitted infections (STIs). SETTING: Online STI testing
      service offered to the residents of Birmingham and Solihull. PARTICIPANTS: All
      patients requesting STI home sampling kits via the Umbrella sexual health service
      website between 15 July 2016 and 14 December 2016. INTERVENTIONS: Associations
      between data collected at online registration and the rate of return of STI home
      sampling kits within 30 days of request was assessed. RESULTS: A total of 5310
      kits were requested, of which 3099 (58.4%) were returned to the medical
      microbiology laboratory. On multivariable analysis, women and men who have sex
      with men were similarly likely to return their sampling kits (adjusted OR (ORadj)
      1.06, 95% CI 0.86 to 1.30), while heterosexual men were significantly less likely
      to return their sampling kits (ORadj 0.63, 95% CI 0.55 to 0.72, p<0.001 vs
      women). Patients reporting symptoms were also less likely to return kits (ORadj
      0.77, 95% CI 0.67 to 0.89, p=0.001 vs asymptomatic patients). Kits that were
      delivered to the patient's home, rather than to a clinic or pharmacy (p<0.001),
      and those requested from less economically deprived neighbourhoods (p=0.029) were
      significantly more likely to be returned. CONCLUSION: STI self-sampling testing
      kits delivered to patients' homes are most likely to be returned. Heterosexual
      men and those from more economically deprived areas are the less likely groups to
      return the kits. Further research on the barriers to return self-sampling STI
      testing kits of these subgroups of patients is warranted. TRIAL REGISTRATION
      NUMBER: Registered with R&D department at University Hospitals Birmingham; CARMS
      13551.

PMID- 29061624
TI  - Right For Me: protocol for a cluster randomised trial of two interventions for
      facilitating shared decision-making about contraceptive methods.
AB  - INTRODUCTION: Despite the observed and theoretical advantages of shared decision
      making in a range of clinical contexts, including contraceptive care, there
      remains a paucity of evidence on how to facilitate its adoption. This paper
      describes the protocol for a study to assess the comparative effectiveness of
      patient-targeted and provider-targeted interventions for facilitating shared
      decision-making about contraceptive methods. METHODS AND ANALYSIS: We will
      conduct a 2*2 factorial cluster randomised controlled trial with four arms: (1)
      video+prompt card, (2) decision aids+training, (3) video+prompt card and decision
      aids+training and (4) usual care. The clusters will be clinics in USA that
      deliver contraceptive care. The participants will be people who have completed a
      healthcare visit at a participating clinic, were assigned female sex at birth,
      are aged 15-49 years, are able to read and write English or Spanish and have not
      previously participated in the study. The primary outcome will be shared decision
      making about contraceptive methods. Secondary outcomes will be the occurrence of
      a conversation about contraception in the healthcare visit, satisfaction with the
      conversation about contraception, intended contraceptive method(s), intention to
      use a highly effective method, values concordance of the intended method(s),
      decision regret, contraceptive method(s) used, use of a highly effective method,
      use of the intended method(s), adherence, satisfaction with the method(s) used,
      unintended pregnancy and unwelcome pregnancy. We will collect study data via
      longitudinal patient surveys administered immediately after the healthcare visit,
      four weeks later and six months later. ETHICS AND DISSEMINATION: We will
      disseminate results via presentations at scientific and professional conferences,
      papers published in peer-reviewed, open-access journals and scientific and lay
      reports. We will also make an anonymised copy of the final participant-level
      dataset available to others for research purposes. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov Identifier: NCT02759939.

PMID- 29061626
TI  - Protocol for establishing an infant feeding database linkable with population
      based administrative data: a prospective cohort study in Manitoba, Canada.
AB  - INTRODUCTION: Breast feeding is associated with many health benefits for mothers
      and infants. But despite extensive public health efforts to promote breast
      feeding, many mothers do not achieve their own breastfeeding goals; and,
      inequities in breastfeeding rates persist between high and low-income mother
      infant dyads. Developing targeted programme to support breastfeeding dyads and
      reduce inequities between mothers of different socioeconomic status are a
      priority for public health practitioners and health policy decision-makers;
      however, many jurisdictions lack the timely and comprehensive population-level
      data on infant-feeding practices required to monitor trends in breastfeeding
      initiation and duration. This protocol describes the establishment of a
      population-based infant-feeding database in the Canadian province of Manitoba,
      providing opportunities to develop and evaluate breastfeeding support programme.
      METHODS AND ANALYSIS: Routinely collected administrative health data on mothers'
      infant-feeding practices will be captured during regular vaccination visits using
      the Teleform fax tool, which converts handwritten information to an electronic
      format. The infant-feeding data will be linked to the Manitoba Population
      Research Data Repository, a comprehensive collection of population-based
      information spanning health, education and social services domains. The linkage
      will allow us to answer research questions about infant-feeding practices and to
      evaluate how effective current initiatives promoting breast feeding are. ETHICS
      AND DISSEMINATION: Approvals have been granted by the Health Research Ethics
      Board at the University of Manitoba. Our integrative knowledge translation
      approach will involve disseminating findings through government and community
      briefings, presenting at academic conferences and publishing in scientific
      journals.

PMID- 29061627
TI  - Smartphone-Enhanced Low-Threshold Intervention for adolescents with Anorexia
      Nervosa (SELTIAN) waiting for outpatient psychotherapy: study protocol of a
      randomised controlled trial.
AB  - INTRODUCTION: As smartphones are widely distributed nowadays, mental health apps
      seem to be a promising treatment tool. First self-help apps for eating disorders
      have been developed recently. However, studies assessing the efficacy of such
      apps are scarce. A smartphone app could prevent further weight reduction and
      increase commitment during waiting time for outpatient treatment, especially for
      adolescents with anorexia nervosa (AN). In this study protocol, a randomised
      controlled trial to assess the efficacy of a smartphone-enhanced low-threshold
      intervention for AN during waiting time is described. METHODS AND ANALYSIS: 30
      adolescents with AN aged 12-19 years will be recruited at three child and
      adolescent psychiatry centres in Germany. All participants will be randomised to
      consultations only or consultations and the use of the Jourvie Research app. The
      app will be installed either on their own smartphone or on a research device. The
      participants will receive biweekly to monthly consultations for 3 months to
      review meal plans and weight management with a clinician. In addition, the
      Jourvie Research app for meal, behaviour and emotion protocolling will be
      provided to the intervention group. The protocols will be discussed with a
      clinician during the consultations. Dialectical behaviour therapy-informed skills
      for tension regulation to increase compliance with the meal plan will be taught
      in the intervention group and the app will remind the participant of a skill in a
      moment of need. The primary outcome is the age-adjusted and height-adjusted
      weight gain in standard deviation score after 3 months. ETHICS AND DISSEMINATION:
      Results will be disseminated at conferences and through peer-reviewed
      publications. The trial was approved by the ethics review board of the local
      medical association, Mainz, Germany, under the reference number 837.338.15. TRIAL
      REGISTRATION NUMBER: German clinical trials register, reference number
      DRKS00008946.

PMID- 29061628
TI  - Views and attitudes towards blood donation: a qualitative investigation of Indian
      non-donors living in England.
AB  - OBJECTIVE: To explore the views and attitudes of Indians living in England on
      blood donation. BACKGROUND: In light of the predicted shortages in blood supply,
      it is vital to consider ways in which to maximise donation rates. These include
      addressing the issue of lower donation rates among ethnic minorities, including
      Indians. However research specifically among minority ethnicities in UK is
      sparse. SETTING: General practice in North London. PARTICIPANTS: A convenience
      sample of 12 non-donor Indians living in England. METHODS: This is a qualitative
      investigation involving semistructured interviews. Themes derived were analysed
      using thematic framework analysis. RESULTS: Five key themes emerged from the
      data, and these concerned participants' perspectives regarding attitudes towards
      blood, blood donation as a 'good thing', donation disincentives, the recipient
      matters and the donor matters. CONCLUSION: A variety of attitudes were presented,
      but were generally positive, and blood was conceptualised in a manner previously
      found to be consistent with donation. However, lack of awareness and
      accessibility were prominent barriers, indicating the need for improvement in
      these capacities. In contrast to this, blood was also greatly associated with
      family and acted as a symbol of kinship: this 'emotional charge' often acted to
      dissuade participants from separating with their blood through donation. Possibly
      due to this, there was also a strong preference for donated blood to be
      distributed within the family, as opposed to strangers. This presents a potential
      barrier to blood donation for some Indians within the current system in which
      donations are given to unknown recipients.

PMID- 29061629
TI  - A longitudinal study to assess the frequency and cost of antivascular endothelial
      therapy, and inequalities in access, in England between 2005 and 2015.
AB  - OBJECTIVES: High-cost antivascular endothelial growth factor (anti-VEGF)
      medicines for eye disorders challenge ophthalmologists and policymakers to
      provide fair access for patients while minimising costs. We describe the growth
      in the use and costs of these medicines and measure inequalities in access.
      DESIGN: Longitudinal study using Hospital Episode Statistics (2005/2006 to
      2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We
      used Poisson regression to estimate standardised rates and explore temporal and
      geographical variations. SETTING: National Health Service (NHS) care in England.
      POPULATION: Patients receiving anti-VEGF injections for age-related macular
      degeneration, diabetic macular oedema and other eye disorders. INTERVENTIONS:
      Higher-cost drugs (ranibizumab or aflibercept) recommended by the National
      Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not
      licensed for eye disorders. MAIN OUTCOME MEASURES: National procedure rates and
      variation between and within clinical commissioning groups (CCGs). Cost of
      ranibizumab and aflibercept prescribing. RESULTS: Injection procedures increased
      by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031
      procedures (714 per 100 000). There is no evidence that the dramatic growth in
      rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and
      aflibercept increased by 247% to L447 million in 2015/2016, equivalent to the
      entire annual budget of a CCG. There are large inequalities in access; in
      2014/2015 procedure rates in a 'high use' CCG were 9.08 times higher than in a
      'low use' CCG. In the South-West of England there was twofold variation in
      injections per patient per year (range 2.9 to 5.9). CONCLUSIONS: The high and
      rising cost of anti-VEGF therapy affects the ability of the NHS to provide care
      for other patients. Current regulations encourage the increasing use of
      ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is
      more cost-effective. NHS patients in England do not have equal access to the most
      cost-effective care.

PMID- 29061630
TI  - Biopsychosocial Intervention for Stroke Carers (BISC): protocol for a feasibility
      randomised controlled trial (RCT).
AB  - INTRODUCTION: Reducing length of hospital stay for stroke survivors often creates
      a shift in the responsibility of care towards informal carers. Adjustment to the
      caregiving process is experienced by many carers as overwhelming, complex and
      demanding and can have a detrimental impact on mental and physical health and
      well-being. National policy guidelines recommend that carers' needs are
      considered and addressed; despite this, few interventions have been developed and
      empirically evaluated. We developed a biopsychosocial intervention in
      collaboration with carers of stroke survivors. Our aim is to determine whether
      the intervention can be delivered in a group setting and evaluated using a
      randomised controlled trial (RCT). METHODS AND ANALYSIS: Feasibility RCT and
      nested qualitative interview study. We aim to recruit up to 40 stroke carers
      within 1 year of the stroke onset. Carers are randomised to usual care or usual
      care plus biopsychosocial intervention. Each intervention group will consist of
      five stroke carers. The intervention will focus on: psychoeducation,
      psychological adjustment to stroke, strategies for reducing unwanted negative
      thoughts and emotions and problem-solving strategies. The main outcome is the
      feasibility of conducting an RCT. Carer outcomes at 6 months include: anxiety and
      depression, quality of life and carer strain. Data are also collected from stroke
      survivors at baseline and 6 months including: level of disability, anxiety and
      depression, and quality of life. ETHICS AND DISSEMINATION: Favourable ethical
      opinion was provided by East Midlands - Nottingham2 Research Ethics Committee
      (14/EMI/1264). This study will determine whether delivery of the biopsychosocial
      intervention is feasible and acceptable to stroke carers within a group format.
      It will also determine whether it is feasible to evaluate the effects of the
      biopsychosocial intervention in an RCT. We will disseminate our findings through
      peer-reviewed publications and presentations at national and international
      conferences. TRIAL REGISTRATION NUMBER: ISRCTN15643456; Pre-results.

PMID- 29061631
TI  - Drug approval status and recommendations for listing on public formularies: a
      Canadian cohort analysis.
AB  - OBJECTIVES: Investigate if the recommendations by the Common Drug Review (CDR)
      and the pan-Canadian Oncology Drug Review (pCODR) to provincial, territorial and
      federal drug plans about whether to list non-oncology and oncology drug
      indication combinations on their formularies are associated with whether the drug
      indication combination was approved via the standard evidence pathway or the
      Notice of Compliance with conditions (NOC/c-limited evidence) pathway. DESIGN:
      Cohort study. DATA SOURCES: Websites of the CDR and pCODR up to the end of 31
      March 2017; journal articles evaluating drugs approved through the NOC/c pathway,
      the NOC database, the NOC/c website and the Summary Basis of Decision website.
      INTERVENTIONS: Recommendations by the CDR and pCODR. PRIMARY AND SECONDARY
      OUTCOME MEASURES: Analysis of the percent of drugs receiving positive listing
      recommendations from CDR and pCODR depending on the pathway used to approve the
      drug. RESULTS: There were 310 recommendations for drug-indication combinations
      from the CDR and 79 from the pCODR. There was a statistically significant
      difference in the number of drug-indication combinations that received a list
      versus do not list recommendation from the CDR for those approved through the
      standard pathway compared with those approved through the NOC/c pathway
      (p=0.0407). A similar analysis for recommendations from the pCODR was not
      statistically significant. CONCLUSION: For non-oncology drug-indication
      combinations, the type of review appears to influence the recommendation
      regarding listing on public formularies. This difference may reflect the level of
      evidence about the efficacy and safety of the drug indication at the time the
      recommendation was made.

PMID- 29061632
TI  - Neoadjuvant S-1 with concurrent radiotherapy followed by surgery for borderline
      resectable pancreatic cancer: study protocol for an open-label, multicentre,
      prospective phase II trial (JASPAC05).
AB  - INTRODUCTION: Borderline resectable pancreatic cancer (BRPC) can involve the
      portal vein, superior mesenteric vein, superior mesenteric artery, coeliac axis
      or hepatic artery, and has a high probability of positive surgical margins and
      poor prognosis after resection. Neoadjuvant chemoradiation is expected to provide
      substantial local control and prolong survival in patients with BRPC. METHODS AND
      ANALYSIS: This open-label, multicentre, prospective phase II trial will assess S
      1 with concurrent radiotherapy as preoperative treatment for BRPC. Participants
      will receive S-1 (40 mg/m2 twice daily) and concurrent radiotherapy (50.4 Gy in
      28 fractions), with restaging and surgery after 3-8 weeks. Recruitment will be
      for a 36-month period with a minimum 24-month follow-up. The primary endpoint is
      the R0 resection rate for BRPC confirmed with central review. The secondary
      endpoints are overall survival, disease-free survival, response rate to
      neoadjuvant chemoradiation, pathological response rate, 2-year survival rate,
      surgical morbidity rate and acute and late toxicity rates. Objectives include
      quantifying the number of participants per year to evaluate whether randomised
      trials can be performed for this rare tumour. ETHICS AND DISSEMINATION: This
      trial has been approved by the National Cancer Center Institutional Review Board.
      Written informed consent will be obtained from all participants. Serious adverse
      events will be reported to the safety desk of the trial, the Data and Safety
      Monitoring Board and trial sites. Trial results will be submitted for peer
      reviewed publication. TRIAL REGISTRATION NUMBER: Pre-results, UMIN000009172.

PMID- 29061633
TI  - Factors associated with quality of life in elderly hospitalised patients
      undergoing post-acute rehabilitation: a cross-sectional analytical study in
      Switzerland.
AB  - OBJECTIVES: We investigated whether biopsychosocial and spiritual factors and
      satisfaction with care were associated with patients' perceived quality of life.
      DESIGN: This was a cross-sectional analytical study. SETTING: Data were collected
      from inpatients at a postacute geriatric rehabilitation centre in a university
      hospital in Switzerland. PARTICIPANTS: Participants aged 65 years and over were
      consecutively recruited from October 2014 to January 2016. Exclusion criteria
      included significant cognitive disorder and terminal illness. Of 227 eligible
      participants, complete data were collected from 167. MAIN OUTCOME MEASURES:
      Perceived quality of life was measured using WHO Quality of Life Questionnaire
      version for older people. Predictive factors were age, sex, functional status at
      admission, comorbidities, cognitive status, depressive symptoms, living
      conditions and satisfaction with care. A secondary focus was the association
      between spiritual needs and quality of life. RESULTS: Patients undergoing
      geriatric rehabilitation experienced a good quality of life. Greater quality of
      life was significantly associated with higher functional status (rs=0.204,
      p=0.011), better cognitive status (rs=0.175, p=0.029) and greater satisfaction
      with care (rs=0.264, p=0.003). Poorer quality of life was significantly
      associated with comorbidities (rs=-.226, p=0.033), greater depressive symptoms
      (rs=-.379, p<0.001) and unmet spiritual needs (rs=-.211, p=0.049). Multivariate
      linear regression indicated that depressive symptoms (beta=-0.961; 95% CIs -1.449
      to 0.472; p<0.001) significantly predicted quality of life. CONCLUSIONS: Patient
      perceptions of quality of life were significantly associated with depression.
      More research is needed to assess whether considering quality of life could
      improve care plan creation.

PMID- 29061634
TI  - Association between statistical significance and time to publication among
      systematic reviews: a study protocol for a meta-epidemiological investigation.
AB  - INTRODUCTION: Many studies have indicated the impact of bias in dissemination and
      publication in medical research. Existence of such bias among clinical trials has
      been repeatedly pointed out, but it has not been well studied in the field of
      systematic reviews (SRs). We therefore aim to investigate whether or not time lag
      bias and publication bias in SRs based on statistical significance in results
      exist. In addition, we will examine at what stage of paper publication process
      such bias, if any, creeps in. METHOD AND ANALYSIS: The present study is a meta
      epidemiological study. We will include all SRs of interventions registered in the
      international prospective register of SRs (PROSPERO) before December 2014 if the
      SR has completed its analysis irrespective of its publication status. All contact
      authors of eligible SRs will be asked to participate in a survey administered
      through the Internet. Our primary outcome is time from protocol registration to
      full publication of SR as a journal article, defined as time from the
      registration date to the acceptance date among all the relevant SRs. We will
      examine the impact of statistically significant findings on the primary outcomes
      through time to event analyses. ETHICS AND DISSEMINATION: Ethics approval will be
      obtained from the Ethical Committee of the Kyoto University Graduate School of
      Medicine. This protocol has been registered in the University Hospital Medical
      Information Network Clinical Trials Registry. We will publish our findings in a
      peer-reviewed journal and also may present them at conferences. TRIAL
      REGISTRATION NUMBER: UMIN000028325.

PMID- 29061635
TI  - The STROBE extensions: protocol for a qualitative assessment of content and a
      survey of endorsement.
AB  - INTRODUCTION: The STrengthening the Reporting of OBservational studies in
      Epidemiology (STROBE) Statement was developed in response to inadequate reporting
      of observational studies. In recent years, several extensions to STROBE have been
      created to provide more nuanced field-specific guidance for authors. The content
      and the prevalence of extension endorsement have not yet been assessed.
      Accordingly, there are two aims: (1) to classify changes made in the extensions
      to identify strengths and weaknesses of the original STROBE checklist and (2) to
      determine the prevalence and typology of endorsement by journals in fields
      related to extensions. METHODS AND ANALYSIS: Two independent researchers will
      assess additions in each extension. Additions will be coded as 'field specific'
      (FS) or 'not field specific' (NFS). FS is defined as particularly relevant
      information for a single field and guidance provided generally cannot be
      extrapolated beyond that field. NFS is defined as information that reflects
      epidemiological or methodological tenets and can be generalised to most, if not
      all, types of observational research studies. Intraclass correlation will be
      calculated to measure reviewers' concordance. On disagreement, consensus will be
      sought. Individual additions will be grouped by STROBE checklist items to
      identify the frequency and distribution of changes.Journals in fields related to
      extensions will be identified through National Library of Medicine PubMed Broad
      Subject Terms, screened for eligibility and further distilled via Ovid MEDLINE(r)
      search strategies for observational studies. Text describing endorsement will be
      extracted from each journal's website. A classification scheme will be created
      for endorsement types and the prevalence of endorsement will be estimated.
      Analyses will use NVivo V.11 and SAS University Edition. ETHICS AND
      DISSEMINATION: This study does not require ethical approval as it does not
      involve human participants. This study has been preregistered on Open Science
      Framework.

PMID- 29061636
TI  - Synaptic input as a directional cue for migrating interneuron precursors.
AB  - During CNS development, interneuron precursors have to migrate extensively before
      they integrate in specific microcircuits. Known regulators of neuronal motility
      include classical neurotransmitters, yet the mechanisms that assure interneuron
      dispersal and interneuron/projection neuron matching during histogenesis remain
      largely elusive. We combined time-lapse video microscopy and electrophysiological
      analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this
      issue. We found that cerebellar interneuronal precursors regularly show
      spontaneous postsynaptic currents, indicative of synaptic innervation, well
      before settling in the molecular layer. In keeping with the sensitivity of these
      cells to neurotransmitters, ablation of synaptic communication by blocking
      vesicular release in acute slices of developing cerebella slows migration.
      Significantly, abrogation of exocytosis primarily impedes the directional
      persistence of migratory interneuronal precursors. These results establish an
      unprecedented function of the early synaptic innervation of migrating neuronal
      precursors and demonstrate a role for synapses in the regulation of migration and
      pathfinding.

PMID- 29061638
TI  - Motor neurons with limb-innervating character in the cervical spinal cord are
      sculpted by apoptosis based on the Hox code in chick embryo.
AB  - In the developing chick embryo, a certain population of motor neurons (MNs) in
      the non-limb-innervating cervical spinal cord undergoes apoptosis between
      embryonic days 4 and 5. However, the characteristics of these apoptotic MNs
      remain undefined. Here, by examining the spatiotemporal profiles of apoptosis and
      MN subtype marker expression in normal or apoptosis-inhibited chick embryos, we
      found that this apoptotic population is distinguishable by Foxp1 expression. When
      apoptosis was inhibited, the Foxp1+ MNs survived and showed characteristics of
      lateral motor column (LMC) neurons, which are of a limb-innervating subtype,
      suggesting that cervical Foxp1+ MNs are the rostral continuation of the LMC.
      Knockdown and misexpression of Foxp1 did not affect apoptosis progression, but
      revealed the role of Foxp1 in conferring LMC identity on the cervical MNs.
      Furthermore, ectopic expression of Hox genes that are normally expressed in the
      brachial region prevented apoptosis, and directed Foxp1+ MNs to LMC neurons at
      the cervical level. These results indicate that apoptosis in the cervical spinal
      cord plays a role in sculpting Foxp1+ MNs committed to LMC neurons, depending on
      the Hox expression pattern.

PMID- 29061637
TI  - Unique developmental trajectories and genetic regulation of ventricular and
      outflow tract progenitors in the zebrafish second heart field.
AB  - During mammalian embryogenesis, cardiac progenitor cells constituting the second
      heart field (SHF) give rise to the right ventricle and primitive outflow tract
      (OFT). In zebrafish, previous lineage-tracing and mutant analyses suggested that
      SHF ventricular and OFT progenitors co-migrate to the arterial pole of the
      zebrafish heart tube soon after their specification in the nkx2.5+ field of
      anterior lateral plate mesoderm (ALPM). Using additional prospective lineage
      tracing, we demonstrate that while SHF ventricular progenitors migrate directly
      to the arterial pole, OFT progenitors become temporarily sequestered in the
      mesodermal cores of pharyngeal arch 2 (PA2), where they downregulate nkx2.5
      expression. While there, they intermingle with precursors for PA2-derived head
      muscles (HMs) and hypobranchial artery endothelium, which we demonstrate are co
      specified with SHF progenitors in the nkx2.5+ ALPM. Soon after their
      sequestration in PA2, OFT progenitors migrate to the arterial pole of the heart
      and differentiate into OFT lineages. Lastly, we demonstrate that SHF ventricular
      and OFT progenitors exhibit unique sensitivities to a mutation in fgf8a Our data
      highlight novel aspects of SHF, OFT and HM development in zebrafish that will
      inform mechanistic interpretations of cardiopharyngeal phenotypes in zebrafish
      models of human congenital disorders.

PMID- 29061639
TI  - Neuronal LRP4 regulates synapse formation in the developing CNS.
AB  - The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in
      muscle fibers for the establishment of the neuromuscular junction. Here, we show
      that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and
      that downregulation of LRP4 in these neurons causes a reduction in density of
      synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in
      cultured neurons had the opposite effect inducing more but shorter primary
      dendrites with an increased number of spines. Transsynaptic tracing mediated by
      rabies virus revealed a reduced number of neurons presynaptic to the cortical
      neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of
      LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons
      with fewer primary dendrites and a lower density of spines in the developing
      cortex and hippocampus. Collectively, our results demonstrate an essential and
      novel role of neuronal LRP4 in dendritic development and synaptogenesis in the
      CNS.

PMID- 29061640
TI  - Lenalidomide Enhances the Function of CS1 Chimeric Antigen Receptor-Redirected T
      Cells Against Multiple Myeloma.
AB  - Purpose: Multiple myeloma remains an incurable malignancy of plasma cells despite
      considerable advances in treatment. The purpose of the study was to develop novel
      chimeric antigen receptors (CAR) for the treatment of multiple myeloma and
      explore combinatorial therapy using CAR T cells and immunomodulatory drugs such
      as lenalidomide for increasing treatment efficacy.Experimental Design: We
      redirected central memory T cells to express second-generation CAR-specific for
      CS1 and adoptively transferred them into multiple myeloma tumor-bearing mice to
      test their anti-multiple myeloma activity. CS1 CAR T cells were transduced and
      expanded in the presence of lenalidomide in vitro The phenotype and effector
      function of CS1 CAR T cells treated with and without lenalidomide were compared.
      Finally, CS1 CAR T cells and lenalidomide were administered to treat multiple
      myeloma-bearing mice as combinatorial therapy.Results: CS1 CAR T cells exhibited
      efficient antitumor activity when adoptively transferred into mice. Mechanistic
      studies indicated that the addition of lenalidomide during CS1 CAR T-cell
      expansion in vitro enhanced the immune functions of CS1 CAR T cells, including
      cytotoxicity, memory maintenance, Th1 cytokine production, and immune synapse
      formation. Furthermore, lenalidomide enhanced the antitumor activity and
      persistence of adoptively transferred CS1 CAR T cells in vivoConclusions: The
      study demonstrates that lenalidomide improves the anti-multiple myeloma
      properties of CS1-directed CAR T cells and provides a basis for a planned
      clinical trial using the combination of lenalidomide with engineered T cells
      against CS1 in relapsed myeloma. Clin Cancer Res; 24(1); 106-19. (c)2017 AACR.

PMID- 29061641
TI  - Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively
      Targets HER2+ Breast Cancer Metastasis to the Brain.
AB  - Purpose: Metastasis to the brain from breast cancer remains a significant
      clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design
      optimization for solid tumors is crucial due to the absence of truly restricted
      antigen expression and potential safety concerns with "on-target off-tumor"
      activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to
      brain metastases, and determined optimal second-generation CAR design and route
      of administration for xenograft mouse models of breast metastatic brain tumors,
      including multifocal and leptomeningeal disease.Experimental Design: HER2-CAR
      constructs containing either CD28 or 4-1BB intracellular costimulatory signaling
      domains were compared for functional activity in vitro by measuring cytokine
      production, T-cell proliferation, and tumor killing capacity. We also evaluated
      HER2-CAR T cells delivered by intravenous, local intratumoral, or regional
      intraventricular routes of administration using in vivo human xenograft models of
      breast cancer that have metastasized to the brain.Results: Here, we have shown
      that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor
      targeting with reduced T-cell exhaustion phenotype and enhanced proliferative
      capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local
      intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in
      orthotopic xenograft models. Importantly, we demonstrated robust antitumor
      efficacy following regional intraventricular delivery of HER2-CAR T cells for the
      treatment of multifocal brain metastases and leptomeningeal disease.Conclusions:
      Our study shows the importance of CAR design in defining an optimized CAR T cell,
      and highlights intraventricular delivery of HER2-CAR T cells for treating
      multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. (c)2017 AACR.

PMID- 29061642
TI  - Multilayered Omics-Based Analysis of a Head and Neck Cancer Model of Cisplatin
      Resistance Reveals Intratumoral Heterogeneity and Treatment-Induced Clonal
      Selection.
AB  - Purpose: Platinum-based drugs, in particular cisplatin (cis
      diamminedichloridoplatinum(II), CDDP), are used for treatment of squamous cell
      carcinoma of the head and neck (SCCHN). Despite initial responses, CDDP treatment
      often results in chemoresistance, leading to therapeutic failure. The role of
      primary resistance at subclonal level and treatment-induced clonal selection in
      the development of CDDP resistance remains unknown.Experimental Design: By
      applying targeted next-generation sequencing, fluorescence in situ hybridization,
      microarray-based transcriptome, and mass spectrometry-based phosphoproteome
      analysis to the CDDP-sensitive SCCHN cell line FaDu, a CDDP-resistant subline,
      and single-cell derived subclones, the molecular basis of CDDP resistance was
      elucidated. The causal relationship between molecular features and resistant
      phenotypes was determined by siRNA-based gene silencing. The clinical relevance
      of molecular findings was validated in patients with SCCHN with recurrence after
      CDDP-based chemoradiation and the TCGA SCCHN dataset.Results: Evidence of primary
      resistance at clonal level and clonal selection by long-term CDDP treatment was
      established in the FaDu model. Resistance was associated with aneuploidy of
      chromosome 17, increased TP53 copy-numbers and overexpression of the gain-of
      function (GOF) mutant variant p53R248L siRNA-mediated knockdown established a
      causal relationship between mutant p53R248L and CDDP resistance. Resistant clones
      were also characterized by increased activity of the PI3K-AKT-mTOR pathway. The
      poor prognostic value of GOF TP53 variants and mTOR pathway upregulation was
      confirmed in the TCGA SCCHN cohort.Conclusions: Our study demonstrates a link of
      intratumoral heterogeneity and clonal evolution as important mechanisms of drug
      resistance in SCCHN and establishes mutant GOF TP53 variants and the PI3K/mTOR
      pathway as molecular targets for treatment optimization. Clin Cancer Res; 24(1);
      158-68. (c)2017 AACR.

PMID- 29061643
TI  - Phase Ib Study of Immune Biomarker Modulation with Neoadjuvant Cetuximab and TLR8
      Stimulation in Head and Neck Cancer to Overcome Suppressive Myeloid Signals.
AB  - Purpose: The response rate of patients with head and neck squamous cell carcinoma
      (HNSCC) to cetuximab therapy is only 15% to 20%, despite frequent EGFR
      overexpression. Because immunosuppression is common in HNSCC, we hypothesized
      that adding a proinflammatory TLR8 agonist to cetuximab therapy might result in
      enhanced T-lymphocyte stimulation and anti-EGFR-specific priming.Experimental
      Design: Fourteen patients with previously untreated HNSCC were enrolled in this
      neoadjuvant trial and treated preoperatively with 3 to 4 weekly doses of
      motolimod (2.5 mg/m2) and cetuximab. Correlative tumor and peripheral blood
      specimens were obtained at baseline and at the time of surgical resection and
      analyzed for immune biomarker changes. Preclinical in vitro studies were also
      performed to assess the effect of cetuximab plus motolimod on myeloid
      cells.Results: TLR8 stimulation skewed monocytes toward an M1 phenotype and
      reversed myeloid-derived suppressor cell (MDSC) suppression of T-cell
      proliferation in vitro These data were validated in a prospective phase Ib
      neoadjuvant trial, in which fewer MDSC and increased M1 monocyte infiltration
      were found in tumor-infiltrating lymphocytes. Motolimod plus cetuximab also
      decreased induction of Treg and reduced markers of suppression, including CTLA-4,
      CD73, and membrane-bound TGFbeta. Significantly increased circulating EGFR
      specific T cells were observed, concomitant with enhanced CD8+ T-cell
      infiltration into tumors. These T cells manifested increased T-cell receptor
      (TCR) clonality, upregulation of the costimulatory receptor CD27, and
      downregulation of inhibitory receptor TIGIT.Conclusions: Enhanced inflammatory
      stimulation in the tumor microenvironment using a TLR agonist overcomes
      suppressive myeloid and regulatory cells, enhancing the cellular antitumor immune
      response by therapeutic mAb in HNSCC. Clin Cancer Res; 24(1); 62-72. (c)2017
      AACR.

PMID- 29061644
TI  - Comprehensive Pharmacogenomic Profiling of Malignant Pleural Mesothelioma
      Identifies a Subgroup Sensitive to FGFR Inhibition.
AB  - Purpose: Despite intense research, treatment options for patients with
      mesothelioma are limited and offer only modest survival advantage. We screened a
      large panel of compounds in multiple mesothelioma models and correlated
      sensitivity with a range of molecular features to detect biomarkers of drug
      response.Experimental design: We utilized a high-throughput chemical inhibitor
      screen in a panel of 889 cancer cell lines, including both immortalized and
      primary early-passage mesothelioma lines, alongside comprehensive molecular
      characterization using Illumina whole-exome sequencing, copy-number analysis and
      Affymetrix array whole transcriptome profiling. Subsequent validation was done
      using functional assays such as siRNA silencing and mesothelioma mouse xenograft
      models.Results: A subgroup of immortalized and primary MPM lines appeared highly
      sensitive to FGFR inhibition. None of these lines harbored genomic alterations of
      FGFR family members, but rather BAP1 protein loss was associated with enhanced
      sensitivity to FGFR inhibition. This was confirmed in an MPM mouse xenograft
      model and by BAP1 knockdown and overexpression in cell line models. Gene
      expression analyses revealed an association between BAP1 loss and increased
      expression of the receptors FGFR1/3 and ligands FGF9/18. BAP1 loss was associated
      with activation of MAPK signaling. These associations were confirmed in a cohort
      of MPM patient samples.Conclusions: A subgroup of mesotheliomas cell lines harbor
      sensitivity to FGFR inhibition. BAP1 protein loss enriches for this subgroup and
      could serve as a potential biomarker to select patients for FGFR inhibitor
      treatment. These data identify a clinically relevant MPM subgroup for
      consideration of FGFR therapeutics in future clinical studies. Clin Cancer Res;
      24(1); 84-94. (c)2017 AACR.

PMID- 29061646
TI  - KRAS Mutation and Consensus Molecular Subtypes 2 and 3 Are Independently
      Associated with Reduced Immune Infiltration and Reactivity in Colorectal Cancer.
AB  - Purpose:KRAS mutation is a common canonical mutation in colorectal cancer, found
      at differing frequencies in all consensus molecular subtypes (CMS). The
      independent immunobiological impacts of RAS mutation and CMS are unknown. Thus,
      we explored the immunobiological effects of KRAS mutation across the CMS
      spectrum.Experimental Design: Expression analysis of immune genes/signatures was
      performed using The Cancer Genome Atlas (TCGA) RNA-seq and the KFSYSCC microarray
      datasets. Multivariate analysis included KRAS status, CMS, tumor location, MSI
      status, and neoantigen load. Protein expression of STAT1, HLA-class II, and
      CXCL10 was analyzed by digital IHC.Results: The Th1-centric co-ordinate immune
      response cluster (CIRC) was significantly, albeit modestly, reduced in KRAS
      mutant colorectal cancer in both datasets. Cytotoxic T cells, neutrophils, and
      the IFNgamma pathway were suppressed in KRAS-mutant samples. The expressions of
      STAT1 and CXCL10 were reduced at the mRNA and protein levels. In multivariate
      analysis, KRAS mutation, CMS2, and CMS3 were independently predictive of reduced
      CIRC expression. Immune response was heterogeneous across KRAS-mutant colorectal
      cancer: KRAS-mutant CMS2 samples have the lowest CIRC expression, reduced
      expression of the IFNgamma pathway, STAT1 and CXCL10, and reduced infiltration of
      cytotoxic cells and neutrophils relative to CMS1 and CMS4 and to KRAS wild-type
      CMS2 samples in the TCGA. These trends held in the KFSYSCC
      dataset.Conclusions:KRAS mutation is associated with suppressed Th1/cytotoxic
      immunity in colorectal cancer, the extent of the effect being modulated by CMS
      subtype. These results add a novel immunobiological dimension to the biological
      heterogeneity of colorectal cancer. Clin Cancer Res; 24(1); 224-33. (c)2017 AACR.

PMID- 29061645
TI  - Homologous Recombination DNA Repair Pathway Disruption and Retinoblastoma Protein
      Loss Are Associated with Exceptional Survival in High-Grade Serous Ovarian
      Cancer.
AB  - Purpose: Women with epithelial ovarian cancer generally have a poor prognosis;
      however, a subset of patients has an unexpected dramatic and durable response to
      treatment. We sought to identify clinical, pathological, and molecular
      determinants of exceptional survival in women with high-grade serous cancer
      (HGSC), a disease associated with the majority of ovarian cancer
      deaths.Experimental Design: We evaluated the histories of 2,283 ovarian cancer
      patients and, after applying stringent clinical and pathological selection
      criteria, identified 96 with HGSC that represented significant outliers in terms
      of treatment response and overall survival. Patient samples were characterized
      immunohistochemically and by genome sequencing.Results: Different patterns of
      clinical response were seen: long progression-free survival (Long-PFS), multiple
      objective responses to chemotherapy (Multiple Responder), and/or greater than 10
      year overall survival (Long-Term Survivors). Pathogenic germline and somatic
      mutations in genes involved in homologous recombination (HR) repair were enriched
      in all three groups relative to a population-based series. However, 29% of 10
      year survivors lacked an identifiable HR pathway alteration, and tumors from
      these patients had increased Ki-67 staining. CD8+ tumor-infiltrating lymphocytes
      were more commonly present in Long-Term Survivors. RB1 loss was associated with
      long progression-free and overall survival. HR deficiency and RB1 loss were
      correlated, and co-occurrence was significantly associated with prolonged
      survival.Conclusions: There was diversity in the clinical trajectory of
      exceptional survivors associated with multiple molecular determinants of
      exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were
      associated with favorable outcomes, suggesting that co-occurrence of specific
      mutations might mediate durable responses in such patients. Clin Cancer Res;
      24(3); 569-80. (c)2017 AACRSee related commentary by Peng and Mills, p. 508.

PMID- 29061648
TI  - Plasma s-Klotho is related to kidney function and predicts adverse renal outcomes
      in patients with advanced chronic kidney disease.
AB  - To investigate whether the soluble Klotho (s-Klotho) level in patients with
      chronic kidney disease (CKD) is related to kidney function and whether a low s
      Klotho level can predict adverse renal outcomes or CKD progression in patients
      with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers
      were enrolled. Blood samples were collected to measure serum creatinine, calcium,
      phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast
      growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross
      sectional study to investigate correlations between s-Klotho and estimated
      glomerular filtration rate (eGFR) and other parameters. Patients were then
      followed prospectively for 20.1+/-10.1 months according to s-Klotho median level
      until serum creatinine doubled, or initiation of renal replacement therapy, or
      death. s-Klotho levels inpatients with CKD were significantly lower than that in
      the control group. For patients with CKD, there were no differences in age
      distribution among subgroups. However, s-Klotho level differed significantly
      across CKD stages, and it was lower in the advanced CKD group compared with the
      moderate CKD group. Correlation analysis revealed that s-Klotho was positively
      associated with eGFR, but inversely associated with FGF23. During the follow-up
      of 20.1+/-10.1 months, patients with higher s-Klotho levels showed a reduced risk
      of kidney adverse outcomes, including serum creatinine doubling and initiation of
      renal replacement therapy. Cox regression analysis revealed that low s-Klotho was
      an independent risk factor for CKD progression. s-Klotho level was closely
      correlated with kidney function, further, low s-Klotho level could predict
      adverse kidney disease outcomes in patients with progressive CKD.

PMID- 29061649
TI  - Retromer revisited: Evolving roles for retromer in endosomal sorting.
AB  - The highly conserved retromer complex has been linked to cargo retrieval from
      endosomes to the trans-Golgi network. In this issue, Kvainickas et al. (2017. J.
      Cell Biol. https://doi.org/10.1083/jcb.201702137) and Simonetti et al. (2017. J.
      Cell Biol. https://doi.org/10.1083/jcb.201703015) fundamentally question the
      current retromer model and demonstrate that in mammalian cells, the individual
      retromer subcomplexes have functionally diverged to organize multiple distinct
      sorting pathways.

PMID- 29061651
TI  - TRPC5 Does Not Cause or Aggravate Glomerular Disease.
AB  - Transient receptor potential channel 5 (TRPC5) is highly expressed in brain and
      kidney and mediates calcium influx and promotes cell migration. In the kidney,
      loss of TRPC5 function has been reported to benefit kidney filter dynamics by
      balancing podocyte cytoskeletal remodeling. However, in vivo gain-in-function
      studies of TRPC5 with respect to kidney function have not been reported. To
      address this gap, we developed two transgenic mouse models on the C57BL/6
      background by overexpressing either wild-type TRPC5 or a TRPC5 ion-pore mutant.
      Compared with nontransgenic controls, neither transgenic model exhibited an
      increase in proteinuria at 8 months of age or a difference in LPS-induced
      albuminuria. Moreover, activation of TRPC5 by Englerin A did not stimulate
      proteinuria, and inhibition of TRPC5 by ML204 did not significantly lower the
      level of LPS-induced proteinuria in any group. Collectively, these data suggest
      that the overexpression or activation of the TRPC5 ion channel does not cause
      kidney barrier injury or aggravate such injury under pathologic conditions.

PMID- 29061647
TI  - Pyridoxine-Dependent Epilepsy in Zebrafish Caused by Aldh7a1 Deficiency.
AB  - Pyridoxine-dependent epilepsy (PDE) is a rare disease characterized by mutations
      in the lysine degradation gene ALDH7A1 leading to recurrent neonatal seizures,
      which are uniquely alleviated by high doses of pyridoxine or pyridoxal 5'
      phosphate (vitamin B6 vitamers). Despite treatment, neurodevelopmental
      disabilities are still observed in most PDE patients underlining the need for
      adjunct therapies. Over 60 years after the initial description of PDE, we report
      the first animal model for this disease: an aldh7a1-null zebrafish (Danio rerio)
      displaying deficient lysine metabolism and spontaneous and recurrent seizures in
      the larval stage (10 days postfertilization). Epileptiform electrographic
      activity was observed uniquely in mutants as a series of population bursts in
      tectal recordings. Remarkably, as is the case in human PDE, the seizures show an
      almost immediate sensitivity to pyridoxine and pyridoxal 5'-phosphate, with a
      resulting extension of the life span. Lysine supplementation aggravates the
      phenotype, inducing earlier seizure onset and death. By using mass spectrometry
      techniques, we further explored the metabolic effect of aldh7a1 knockout.
      Impaired lysine degradation with accumulation of PDE biomarkers, B6 deficiency,
      and low gamma-aminobutyric acid levels were observed in the aldh7a1-/- larvae,
      which may play a significant role in the seizure phenotype and PDE pathogenesis.
      This novel model provides valuable insights into PDE pathophysiology; further
      research may offer new opportunities for drug discovery to control seizure
      activity and improve neurodevelopmental outcomes for PDE.

PMID- 29061653
TI  - Triaging in the face of terror.

PMID- 29061652
TI  - Progressive Renal Disease Established by Renin-Coding Adeno-Associated Virus
      Driven Hypertension in Diverse Diabetic Models.
AB  - Progress in research and developing therapeutics to prevent diabetic kidney
      disease (DKD) is limited by a lack of animal models exhibiting progressive kidney
      disease. Chronic hypertension, a driving factor of disease progression in human
      patients, is lacking in most available models of diabetes. We hypothesized that
      superimposition of hypertension on diabetic mouse models would accelerate DKD. To
      test this possibility, we induced persistent hypertension in three mouse models
      of type 1 diabetes and two models of type 2 diabetes by adeno-associated virus
      delivery of renin (ReninAAV). Compared with LacZAAV-treated counterparts,
      ReninAAV-treated type 1 diabetic Akita/129 mice exhibited a substantial increase
      in albumin-to-creatinine ratio (ACR) and serum creatinine level and more severe
      renal lesions. In type 2 models of diabetes (C57BKLS db/db and BTBR ob/ob mice),
      compared with LacZAAV, ReninAAV induced significant elevations in ACR and
      increased the incidence and severity of histopathologic findings, with increased
      serum creatinine detected only in the ReninAAV-treated db/db mice. The
      uninephrectomized ReninAAV db/db model was the most progressive model examined
      and further characterized. In this model, separate treatment of hyperglycemia
      with rosiglitazone or hypertension with lisinopril partially reduced ACR,
      consistent with independent contributions of these disorders to renal disease.
      Microarray analysis and comparison with human DKD showed common pathways affected
      in human disease and this model. These results identify novel models of
      progressive DKD that provide researchers with a facile and reliable method to
      study disease pathogenesis and support the development of therapeutics.

PMID- 29061654
TI  - Doctor whose scrubs emitted smell of alcohol is cleared of drink driving.

PMID- 29061650
TI  - Rac3 regulates breast cancer invasion and metastasis by controlling adhesion and
      matrix degradation.
AB  - The initial step of metastasis is the local invasion of tumor cells into the
      surrounding tissue. Invadopodia are actin-based protrusions that mediate the
      matrix degradation necessary for invasion and metastasis of tumor cells. We
      demonstrate that Rac3 GTPase is critical for integrating the adhesion of
      invadopodia to the extracellular matrix (ECM) with their ability to degrade the
      ECM in breast tumor cells. We identify two pathways at invadopodia important for
      integrin activation and delivery of matrix metalloproteinases: through the
      upstream recruiter CIB1 as well as the downstream effector GIT1. Rac3 activity,
      at and surrounding invadopodia, is controlled by Vav2 and betaPIX. These guanine
      nucleotide exchange factors regulate the spatiotemporal dynamics of Rac3
      activity, impacting GIT1 localization. Moreover, the GTPase-activating function
      of GIT1 toward the vesicular trafficking regulator Arf6 GTPase is required for
      matrix degradation. Importantly, Rac3 regulates the ability of tumor cells to
      metastasize in vivo. The Rac3-dependent mechanisms we show in this study are
      critical for balancing proteolytic activity and adhesive activity to achieve a
      maximally invasive phenotype.

PMID- 29061655
TI  - Public mental health crisis management and Section 136 of the Mental Health Act.
AB  - The interface between mental health services and the criminal justice system
      presents challenges both for professionals and patients. Both systems are
      stressed and inherently complex. Section 136 of the Mental Health Act is unusual
      being both an aspect of the Mental Health Act and a power of arrest. It has a
      long and controversial history related to concerns about who has been detained
      and how the section was applied. More recently, Section 136 has had a public
      profile stemming from the use of police cells as places of safety for young,
      mentally disturbed individuals. This paper explores the current state of health
      of this piece of legislation. Specifically, we consider whether alternative
      approaches are more suitable for those individuals in crisis and/or distress who
      come into contact with the police. This requires careful thought as to the proper
      role of both health and criminal justice professionals who are daily grappling
      with an ethically contentious domain of multiagency work.

PMID- 29061657
TI  - In This Issue of Diabetes.

PMID- 29061656
TI  - Synergistic Antiproliferative Activity of the RAD51 Inhibitor IBR2 with
      Inhibitors of Receptor Tyrosine Kinases and Microtubule Protein.
AB  - Although cancer cell genetic instability contributes to characteristics that
      mediate tumorigenicity, it also contributes to the tumor-selective toxicity of
      some chemotherapy drugs. This synthetic lethality can be enhanced by inhibitors
      of DNA repair. To exploit this potential Achilles heel, we tested the ability of
      a RAD51 inhibitor to potentiate the cytotoxicity of chemotherapy drugs. 2
      (Benzylsulfonyl)-1-(1H-indol-3-yl)-1,2-dihydroisoquinoline (IBR2) inhibits RAD51
      mediated DNA double-strand break repair but also enhances cytotoxicity of the Bcr
      Abl inhibitor imatinib. The potential for synergy between IBR2 and more drugs was
      examined in vitro across a spectrum of cancer cell lines from various tissues.
      Cells were exposed to IBR2 simultaneously with inhibitors of receptor tyrosine
      kinases, DNA-damaging agents, or microtubule disruptors. IBR2, at concentrations
      that inhibited proliferation between 0% and 75%, enhanced toxicity by up to 80%
      of imatinib and regorafenib (targets RAF and kit); epidermal growth factor
      receptor inhibitors erlotinib, gefitinib, afatinib, and osimertinib; and
      vincristine, an inhibitor of microtubule function. However, IBR2 antagonized the
      action of olaparib, cisplatin, melphalan, and irinotecan. A vincristine-resistant
      squamous cell line was not cross resistant to imatinib, but IBR2 and another
      RAD51 inhibitor (B02) enhanced imatinib toxicity in this cell line, its HN-5a
      parent, and the colon cancer line HT-29 by up to 60% and much better than
      verapamil, a P-glycoprotein inhibitor (P < 0.05). Given the disparate agents the
      functions of which are enhanced by IBR2, the mechanisms of enhancement may be
      multimodal. Whether RAD51 is common to these mechanisms remains to be elucidated,
      but it provides the potential for selectivity to tumor cells.

PMID- 29061658
TI  - The Gastrointestinal Tract as an Integrator of Mechanical and Hormonal Response
      to Nutrient Ingestion.
AB  - Glucose tolerance after meal ingestion in vivo is the result of multiple
      processes that occur in parallel. Insulin secretion together with reciprocal
      inhibition of glucagon secretion contributes to glucose tolerance. However, other
      factors beyond glucose effectiveness and insulin action require consideration.
      The absorption of ingested nutrients and their subsequent systemic rate of
      appearance largely depend on the rate of delivery of nutrients to the proximal
      small intestine. This is determined by the integrated response of the upper
      gastrointestinal tract to a meal. While gastric emptying is probably the most
      significant component, other factors need to be considered. This review will
      examine all processes that could potentially alter the fraction and rate of
      appearance of ingested nutrients in the peripheral circulation. Several of these
      processes may be potential therapeutic targets for the prevention and treatment
      of diabetes. Indeed, there is increased interest in gastrointestinal
      contributions to nutritional homeostasis, as demonstrated by the advent of
      antidiabetes therapies that alter gastrointestinal motility, the effect of
      bariatric surgery on diabetes remission, and the potential of the intestinal
      microbiome as a modulator of human metabolism. The overall goal of this review is
      to examine current knowledge of the gastrointestinal contributions to metabolic
      control.

PMID- 29061660
TI  - Give GWAS a Chance.

PMID- 29061659
TI  - Area IV Knockout Reveals How Pdx1 Is Regulated in Postnatal beta-Cell
      Development.

PMID- 29061661
TI  - Long-term Hyperglycemia Naturally Induces Dental Caries but Not Periodontal
      Disease in Type 1 and Type 2 Diabetic Rodents.
AB  - Periodontal disease (PD) in patients with diabetes is described as the sixth
      complication of diabetes. We have previously shown that diabetes increases dental
      caries, and carious inflammation might have a strong effect on the adjacent
      periodontal tissue in diabetic rodent models. However, the possibility that
      hyperglycemia may induce PD in diabetic animals could not be completely
      eliminated. The goal of this study was to confirm the presence of PD in diabetic
      animal models by preventing carious inflammation with fluoride administration.
      F344 rats injected with alloxan (type 1 diabetic model) and db/db mice (type 2
      diabetic model) were given either tap water alone or tap water containing
      fluoride. A cariostatic effect of fluoride was evident in the diabetic animals.
      Meanwhile, fluoride treatment drastically attenuated periodontal inflammation in
      addition to preventing dental caries. Furthermore, with fluoride treatment,
      periodontitis was notably nonexistent in the periodontal tissue surrounding the
      normal molars, whereas the caries-forming process was clearly observed in the
      teeth that were enveloped with persistent periodontitis, suggesting that enhanced
      periodontal inflammation might have been derived from the dental caries in the
      diabetic rodents rather than from the PD. In conclusion, long-term hyperglycemia
      naturally induces dental caries but not PD in type 1 and type 2 diabetic rodents.

PMID- 29061663
TI  - SwrD (YlzI) Promotes Swarming in Bacillus subtilis by Increasing Power to
      Flagellar Motors.
AB  - The bacterium Bacillus subtilis is capable of two kinds of flagellum-mediated
      motility: swimming, which occurs in liquid, and swarming, which occurs on a
      surface. Swarming is distinct from swimming in that it requires secretion of a
      surfactant, an increase in flagellar density, and perhaps additional factors.
      Here we report a new gene, swrD, located within the 32 gene fla-che operon
      dedicated to flagellar biosynthesis and chemotaxis, which when mutated abolished
      swarming motility. SwrD was not required for surfactant production, flagellar
      gene expression, or an increase in flagellar number. Instead, SwrD was required
      to increase flagellar power. Mutation of swrD reduced swimming speed and torque
      of tethered flagella, and all swrD-related phenotypes were restored when the
      stator subunits MotA and MotB were overexpressed either by spontaneous suppressor
      mutations or by artificial induction. We conclude that swarming motility requires
      flagellar power in excess of that which is needed to swim.IMPORTANCE Bacteria
      swim in liquid and swarm over surfaces by rotating flagella, but the difference
      between swimming and swarming is poorly understood. Here we report that SwrD of
      Bacillus subtilis is necessary for swarming because it increases flagellar torque
      and cells mutated for swrD swim with reduced speed. How flagellar motors generate
      power is primarily studied in Escherichia coli, and SwrD likely increases power
      in other organisms, like the Firmicutes, Clostridia, Spirochaetes, and the
      Deltaproteobacteria.

PMID- 29061664
TI  - BtsT - a novel and specific pyruvate/H+ symporter in Escherichia coli.
AB  - The CstA (the peptide transporter carbon starvation CstA family; TC# 2.A.114)
      family of peptide transporters belongs to the second largest superfamily of
      secondary transporters, the amino acid/polyamine/organocation (APC) superfamily.
      No representative of the CstA family has previously been characterized either
      biochemically or structurally, but we have now identified the function of one of
      its members, the transport protein YjiY of Escherichia coli Expression of the
      yjiY gene is regulated by the LytS-like histidine kinase BtsS, a sensor of
      extracellular pyruvate, together with the LytTR-like response regulator BtsR.
      YjiY consists of 716 amino acids, which form 18 putative transmembrane helices.
      Transport studies with intact cells provided evidence that YjiY is a specific and
      high-affinity transporter for pyruvate (Km 16 MUM). Furthermore, reconstitution
      of the purified YjiY into proteoliposomes revealed that YjiY is a pyruvate/H+
      symporter. It has long been assumed that E. coli possesses transporter(s) for
      pyruvate, but the present study is the first to definitively identify such a
      protein. Based on its function, we propose to rename the uncharacterized gene
      yjiY as btsT (for "Brenztraubensaure" transporter, from the German word for
      pyruvate).IMPORTANCE BtsT (formerly known as YjiY) is found in many commensal and
      pathogenic representatives of the Enterobacteriaceae This study for the first
      time characterizes a pyruvate transporter in Escherichia coli, BtsT, as a
      specific pyruvate/H+ symporter. When nutrients are limiting, BtsT takes up
      pyruvate from the medium, thus enabling it to be used as a carbon source for the
      growth and survival of E. coli.

PMID- 29061665
TI  - DksA and ppGpp Regulate the sigmaS Stress Response by Activating Promoters for
      the Small RNA DsrA and the Anti-Adapter Protein IraP.
AB  - sigmaS is an alternative sigma factor, encoded by the rpoS gene, that redirects
      cellular transcription to a large family of genes in response to stressful
      environmental signals. This so-called sigmaS general stress response is necessary
      for survival in many bacterial species and is controlled by a complex,
      multifactorial pathway that regulates sigmaS levels transcriptionally,
      translationally, and post-translationally in Escherichia coli It was shown
      previously that the transcription factor DksA and its cofactor ppGpp are among
      the many factors governing sigmaS synthesis, thus playing an important role in
      activation of the sigmaS stress response. However, the mechanisms responsible for
      the effects of DksA and ppGpp have not been elucidated fully. We describe here
      how DksA and ppGpp directly activate the promoters for the anti-adaptor protein
      IraP and the small regulatory RNA DsrA, thereby indirectly influencing sigmaS
      levels. In addition, based on effects of DksAN88I, a previously identified DksA
      variant with increased affinity for RNAP, we show that DksA can increase sigmaS
      activity by another indirect mechanism. We propose that by reducing rRNA
      transcription, DksA and ppGpp increase the availability of core RNAP for binding
      to sigmaS and also increase transcription from other promoters, including PdsrA
      and PiraP By improving the translation and stabilization of sigmaS, as well as
      the ability of other promoters to compete for RNAP, DksA and ppGpp contribute to
      the switch in the transcription program needed for stress adaptation.IMPORTANCE
      Bacteria spend relatively little time in log phase outside of the optimized
      environment found in a laboratory. They have evolved to make the most of
      alternating feast and famine conditions by seamlessly transitioning between rapid
      growth and stationary phase, a lower metabolic mode that is crucial for long-term
      survival. One of the key regulators of the switch in gene expression that
      characterizes stationary phase is the alternative sigma factor sigmaS
      Understanding the factors governing sigmaS activity is central to unraveling the
      complexities of growth, adaptation to stress, and pathogenesis. Here we describe
      three mechanisms by which the RNA polymerase binding factor DksA and the second
      messenger ppGpp regulate sigmaS levels.

PMID- 29061666
TI  - Suppression of a Thermosensitive zipA Cell Division Mutant by Altering Amino Acid
      Metabolism.
AB  - ZipA is essential for cell division in Escherichia coli, acting early in the
      process to anchor polymers of FtsZ to the cytoplasmic membrane. Along with FtsA,
      FtsZ and ZipA form a proto-ring at midcell that recruits additional proteins to
      eventually build the division septum. Cells carrying the thermosensitive zipA1
      allele divide fairly normally at 30 degrees C in rich medium but cease dividing
      at temperatures above 34 degrees C, forming long filaments. In a search for
      suppressors of the zipA1 allele, we found that deletions of specific genes
      involved in amino acid biosynthesis could partially rescue cell growth and
      division at 34 degrees C or 37 degrees C but not at 42 degrees C. Notably,
      although a diverse group of amino acid biosynthesis gene deletions could
      partially rescue the growth of zipA1 cells at 34 degrees C, only deletions of
      genes related to the biosynthesis of threonine, glycine, serine, and methionine
      could rescue growth at 37 degrees C. Adding exogenous pyridoxal 5-phosphate
      (PLP), a cofactor for many of the enzymes affected by this study, partially
      suppressed zipA1 mutant thermosensitivity. For many of the deletions, PLP had an
      additive rescuing effect on the zipA1 mutant. Moreover, added PLP partially
      suppressed the thermosensitivity of ftsQ and ftsK mutants and weakly suppressed
      an ftsI mutant, but it failed to suppress ftsA or ftsZ thermosensitive mutants.
      Along with the ability of a deletion of metC to partially suppress the ftsK
      mutant, our results suggest that perturbations of amino acid metabolic pathways,
      particularly those that redirect the flow of carbon away from the synthesis of
      threonine, glycine, or methionine, are able to partially rescue some cell
      division defects.IMPORTANCE Cell division of bacteria, such as Escherichia coli,
      is essential for their successful colonization. It is becoming increasingly clear
      that nutritional status and central metabolism can affect bacterial size and
      shape; for example, a metabolic enzyme (OpgH) can moonlight as a regulator of
      FtsZ, an essential cell division protein. Here, we demonstrate a link between
      amino acid metabolism and ZipA, another essential cell division protein that
      binds directly to FtsZ and tethers it to the cytoplasmic membrane. Our evidence
      suggests that altering flux through the methionine-threonine-glycine-serine
      pathways and supplementing with the enzyme cofactor pyridoxal-5-phosphate can
      partially compensate for an otherwise lethal defect in ZipA, as well as several
      other cell division proteins.

PMID- 29061667
TI  - Novel YAP1 Activator, Identified by Transcription-Based Functional Screen, Limits
      Multiple Myeloma Growth.
AB  - Yes-associated protein 1 (YAP1) interacts with numerous transcription factors,
      including TEA-domain family proteins (TEAD) and p73. YAP1 is negatively regulated
      by the tumor suppressor Hippo pathway. In human cancers, the deregulation of the
      Hippo pathway and YAP1 gene amplification lead to the activation of YAP1, which
      induces epithelial-mesenchymal transition (EMT) and drug resistance. YAP1
      inhibitors are expected to be useful in cancer therapy. On the other hand, in
      certain cancers, YAP1 upregulates p73-dependent gene transcription and behaves as
      a tumor suppressor. Moreover, as YAP1 regulates self-renewal and differentiation
      of tissue stem cells and plays an important role in tissue homeostasis, YAP1
      activators may contribute to the regenerative medicine. With this in our mind, we
      screened for YAP1 activators by using human retinal pigment epithelial ARPE-19
      cells expressing the TEAD-responsive fluorescence reporter under the coexpression
      of YAP1. From an extensive chemical compound library (n = 18,606) 47 candidate
      YAP1 activators were identified. These compounds were characterized to determine
      whether this assay provides bona fide YAP1 activators. Importantly, one YAP1
      activator was effective against the human multiple myeloma IM-9 cells and chronic
      myeloid leukemia K562 cells.Implications: YAP1 activation limits growth, induces
      apoptosis, and may be useful at suppressing hematological cancers. Mol Cancer
      Res; 16(2); 197-211. (c)2017 AACR.

PMID- 29061668
TI  - Drug detoxification dynamics explain the postantibiotic effect.
AB  - The postantibiotic effect (PAE) refers to the temporary suppression of bacterial
      growth following transient antibiotic treatment. This effect has been observed
      for decades for a wide variety of antibiotics and microbial species. However,
      despite empirical observations, a mechanistic understanding of this phenomenon is
      lacking. Using a combination of modeling and quantitative experiments, we show
      that the PAE can be explained by the temporal dynamics of drug detoxification in
      individual cells after an antibiotic is removed from the extracellular
      environment. These dynamics are dictated by both the export of the antibiotic and
      the intracellular titration of the antibiotic by its target. This mechanism is
      generally applicable for antibiotics with different modes of action. We further
      show that efflux inhibition is effective against certain antibiotic motifs, which
      may help explain mixed cotreatment success.

PMID- 29061670
TI  - Ready, Set...Poised!: Polycomb target genes are bound by poised RNA polymerase II
      throughout differentiation.

PMID- 29061671
TI  - Meiosis-like Functions in Oncogenesis: A New View of Cancer.
AB  - Cancer cells have many abnormal characteristics enabling tumors to grow, spread,
      and avoid immunologic and therapeutic destruction. Central to this is the innate
      ability of populations of cancer cells to rapidly evolve. One feature of many
      cancers is that they activate genes that are normally associated with distinct
      developmental states, including germ cell-specific genes. This has historically
      led to the proposal that tumors take on embryonal characteristics, the so called
      embryonal theory of cancer. However, one group of germline genes, not directly
      associated with embryonic somatic tissue genesis, is the one that encodes the
      specific factors to drive the unique reductional chromosome segregation of
      meiosis I, which also results in chromosomal exchanges. Here, we propose that
      meiosis I-specific modulators of reductional segregation can contribute to
      oncogenic chromosome dynamics and that the embryonal theory for cancer cell
      growth/proliferation is overly simplistic, as meiotic factors are not a feature
      of most embryonic tissue development. We postulate that some meiotic chromosome
      regulatory functions contribute to a soma-to-germline model for cancer, in which
      activation of germline (including meiosis) functions drive oncogenesis, and we
      extend this to propose that meiotic factors could be powerful sources of targets
      for therapeutics and biomonitoring in oncology. Cancer Res; 77(21); 5712-6.
      (c)2017 AACR.

PMID- 29061669
TI  - Lysine acetylome profiling uncovers novel histone deacetylase substrate proteins
      in Arabidopsis.
AB  - Histone deacetylases have central functions in regulating stress defenses and
      development in plants. However, the knowledge about the deacetylase functions is
      largely limited to histones, although these enzymes were found in diverse
      subcellular compartments. In this study, we determined the proteome-wide
      signatures of the RPD3/HDA1 class of histone deacetylases in Arabidopsis Relative
      quantification of the changes in the lysine acetylation levels was determined on
      a proteome-wide scale after treatment of Arabidopsis leaves with deacetylase
      inhibitors apicidin and trichostatin A. We identified 91 new acetylated candidate
      proteins other than histones, which are potential substrates of the RPD3/HDA1
      like histone deacetylases in Arabidopsis, of which at least 30 of these proteins
      function in nucleic acid binding. Furthermore, our analysis revealed that histone
      deacetylase 14 (HDA14) is the first organellar-localized RPD3/HDA1 class protein
      found to reside in the chloroplasts and that the majority of its protein targets
      have functions in photosynthesis. Finally, the analysis of HDA14 loss-of-function
      mutants revealed that the activation state of RuBisCO is controlled by lysine
      acetylation of RuBisCO activase under low-light conditions.

PMID- 29061672
TI  - miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in
      Colon Cancer Cells.
AB  - CDK4/6 targeting is a promising therapeutic strategy under development for
      various tumor types. In this study, we used computational methods and The Cancer
      Genome Atlas dataset analysis to identify novel miRNAs that target CDK4/6 and
      exhibit potential for therapeutic development in colorectal cancer. The 3'UTR of
      CDK4/6 mRNAs are targeted by a family of miRNAs, which includes miR-6883-5p, miR
      149*, miR-6785-5p, and miR-4728-5p. Ectopic expression of miR-6883-5p or miR-149*
      downregulated CDK4 and CDK6 levels in human colorectal cancer cells. RNA-seq
      analysis revealed an inverse relationship between the expression of CDK4/6 and
      miR-149* and intronic miRNA-6883-5p encoding the clock gene PER1 in colorectal
      cancer patient samples. Restoring expression of miR-6883-5p and miR-149* blocked
      cell growth leading to G0-G1 phase cell-cycle arrest and apoptosis in colorectal
      cancer cells. CDK4/6 targeting by miR-6883-5p and miR-149* could only partially
      explain the observed antiproliferative effects. Notably, both miRNAs synergized
      with the frontline colorectal cancer chemotherapy drug irinotecan. Further, they
      resensitized mutant p53-expressing cell lines resistant to 5-fluorouracil. Taken
      together, our results established the foundations of a candidate miRNA-based
      theranostic strategy to improve colorectal cancer management. Cancer Res; 77(24);
      6902-13. (c)2017 AACR.

PMID- 29061674
TI  - Head flutter.

PMID- 29061673
TI  - Pilocytic astrocytoma with anaplasia arising from the optic chiasm in a very
      elderly patient.

PMID- 29061675
TI  - Editors' Note.

PMID- 29061676
TI  - Letter re: Alterations of functional connectivity of the motor cortex in Fabry
      disease: An RS-fMRI study.

PMID- 29061677
TI  - Author response: Alterations of functional connectivity of the motor cortex in
      Fabry disease: An RS-fMRI study.

PMID- 29061678
TI  - Letter re: Teaching NeuroImages: Acute Parinaud syndrome.

PMID- 29061680
TI  - Genetics, white matter, and cognition: The effects of methylation on FMR1.

PMID- 29061679
TI  - Author response: Teaching NeuroImages: Acute Parinaud syndrome.

PMID- 29061681
TI  - Clinical Reasoning: A common cause for Phelan-McDermid syndrome and
      neurofibromatosis type 2: One ring to bind them.

PMID- 29061682
TI  - Pearls & Oy-sters: CNS lymphoma in a patient with relapsing-remitting multiple
      sclerosis treated with interferon.

PMID- 29061684
TI  - Teaching NeuroImages: New-onset focal epilepsy: The curious case of the camel and
      the jawbone.

PMID- 29061683
TI  - Teaching NeuroImages: Hypoglossal nerve palsy due to basilar invagination.

PMID- 29061685
TI  - Neuromuscular mechanisms of an elaborate wing display in the golden-collared
      manakin (Manacus vitellinus).
AB  - Many species perform elaborate physical displays to court mates and compete with
      rivals, but the biomechanical mechanisms underlying such behavior are poorly
      understood. We address this issue by studying the neuromuscular origins of
      display behavior in a small tropical passerine bird, the golden-collared manakin
      (Manacus vitellinus). Males of this species court females by dancing around the
      forest floor and rapidly snapping their wings together above their back. Using
      radio-telemetry, we collected electromyographic (EMG) recordings from the three
      main muscles that control avian forelimb movement, and found how these different
      muscles are activated to generate various aspects of display behavior. The muscle
      that raises the wing (supracoracoideus, SC) and the primary muscle that retracts
      the wing (scapulohumeralis caudalis, SH) were activated during the wing-snap,
      whereas the pectoralis (PEC), the main wing depressor, was not. SC activation
      began before wing elevation commenced, with further activation occurring
      gradually. By contrast, SH activation was swift, starting soon after wing
      elevation and peaking shortly after the snap. The intensity of this SH activation
      was comparable to that which occurs during flapping, whereas the SC activation
      was much lower. Thus, light activation of the SC likely helps position the wings
      above the back, so that quick, robust SH activation can drive these appendages
      together to generate the firecracker-like snap sonation. This is one of the first
      looks at the neuromuscular mechanisms that underlie the actuation of a dynamic
      courtship display, and it demonstrates that even complex, whole-body display
      movements can be studied with transmitter-aided EMG techniques.

PMID- 29061686
TI  - Myogenic activity and serotonergic inhibition in the chromatophore network of the
      squid Dosidicus gigas (family Ommastrephidae) and Doryteuthis opalescens (family
      Loliginidae).
AB  - Seemingly chaotic waves of spontaneous chromatophore activity occur in the
      ommastrephid squid Dosidicus gigas in the living state and immediately after
      surgical disruption of all known inputs from the central nervous system. Similar
      activity is apparent in the loliginid Doryteuthis opalescens, but only after
      chronic denervation of chromatophores for 5-7 days. Electrically stimulated,
      neurally driven activity in intact individuals of both species is blocked by
      tetrodotoxin (TTX), but TTX has no effect on spontaneous wave activity in either
      D. gigas or denervated D. opalescens Spontaneous TTX-resistant activity of this
      sort is therefore likely myogenic, and such activity is eliminated in both
      preparations by serotonin (5-HT), a known inhibitor of chromatophore activity.
      Immunohistochemical techniques reveal that individual axons containing L
      glutamate or 5-HT (and possibly both in a minority of processes) are associated
      with radial muscle fibers of chromatophores in intact individuals of both
      species, although the area of contact between both types of axons and muscle
      fibers is much smaller in D. gigas Glutamatergic and serotonergic axons
      degenerate completely following denervation in D. opalescens Spontaneous waves of
      chromatophore activity in both species are thus associated with reduced (or no)
      serotonergic input in comparison to the situation in intact D. opalescens Such
      differences in the level of serotonergic inhibition are consistent with natural
      chromogenic behaviors in these species. Our findings also suggest that such
      activity might propagate via the branching distal ends of radial muscle fibers.

PMID- 29061688
TI  - Managing the Eisenmenger syndrome: a call to arms.

PMID- 29061689
TI  - Renin-angiotensin system blockade after TAVI: is there a link between regression
      of left ventricular hypertrophy and prognosis?

PMID- 29061687
TI  - Environmental effects on Drosophila brain development and learning.
AB  - Brain development and behavior are sensitive to a variety of environmental
      influences including social interactions and physicochemical stressors. Sensory
      input in situ is a mosaic of both enrichment and stress, yet little is known
      about how multiple environmental factors interact to affect brain anatomical
      structures, circuits and cognitive function. In this study, we addressed these
      issues by testing the individual and combined effects of sub-adult thermal
      stress, larval density and early-adult living spatial enrichment on brain anatomy
      and olfactory associative learning in adult Drosophila melanogaster In response
      to heat stress, the mushroom bodies (MBs) were the most volumetrically impaired
      among all of the brain structures, an effect highly correlated with reduced odor
      learning performance. However, MBs were not sensitive to either larval culture
      density or early-adult living conditions. Extreme larval crowding reduced the
      volume of the antennal lobes, optic lobes and central complex. Neither larval
      crowding nor early-adult spatial enrichment affected olfactory learning. These
      results illustrate that various brain structures react differently to
      environmental inputs, and that MB development and learning are highly sensitive
      to certain stressors (pre-adult hyperthermia) and resistant to others (larval
      crowding).

PMID- 29061691
TI  - Obstructive left main stem coronary disease: is it time to recommend coronary
      stenting?

PMID- 29061690
TI  - Molecular imaging of atherosclerosis: spotlight on Raman spectroscopy and surface
      enhanced Raman scattering.
AB  - To accurately predict atherosclerotic plaque progression, a detailed phenotype of
      the lesion at the molecular level is required. Here, we assess the respective
      merits and limitations of molecular imaging tools. Clinical imaging includes
      contrast-enhanced ultrasound, an inexpensive and non-toxic technique but with
      poor sensitivity. CT benefits from high spatial resolution but poor sensitivity
      coupled with an increasing radiation burden that limits multiplexing. Despite
      high sensitivity, positron emission tomography and single-photon emission
      tomography have disadvantages when applied to multiplex molecular imaging due to
      poor spatial resolution, signal cross talk and increasing radiation dose. In
      contrast, MRI is non-toxic, displays good spatial resolution but poor
      sensitivity. Preclinical techniques include near-infrared fluorescence (NIRF),
      which provides good spatial resolution and sensitivity; however, multiplexing
      with NIRF is limited, due to photobleaching and spectral overlap. Fourier
      transform infrared spectroscopy and Raman spectroscopy are label-free techniques
      that detect molecules based on the vibrations of chemical bonds. Both techniques
      offer fast acquisition times with Raman showing superior spatial resolution.
      Raman signals are inherently weak; however, leading to the development of surface
      enhanced Raman spectroscopy (SERS) that offers greatly increased sensitivity due
      to using metallic nanoparticles that can be functionalised with biomolecules
      targeted against plaque ligands while offering high multiplexing potential. This
      asset combined with high spatial resolution makes SERS an exciting prospect as a
      diagnostic tool. The ongoing refinements of SERS technologies such as deep tissue
      imaging and portable systems making SERS a realistic prospect for translation to
      the clinic.

PMID- 29061692
TI  - A new lead to NLRP3 inhibition.
AB  - The discovery of a small molecule inhibitor that targets the inflammasome sensor
      NLRP3 offers a new path for the development of selective inflammasome blockers
      with potential therapeutic benefit in a wide range of human diseases (in this
      issue, see Jiang et al., https://doi.org/10.1084/jem.20171419).

PMID- 29061694
TI  - BASHH HealthUnlocked.

PMID- 29061695
TI  - Increases in gonorrhoea incidence and GUM clinic waiting times: are we in a
      vicious circle like the late 1990s and early 2000s, but now exacerbated by drug
      resistance?

PMID- 29061697
TI  - How many MSM are taking PrEP: a service evaluation.

PMID- 29061696
TI  - Resistant herpes simplex type 2 treated with varicella zoster vaccination.

PMID- 29061698
TI  - The Right Temporoparietal Junction Supports Speech Tracking During Selective
      Listening: Evidence from Concurrent EEG-fMRI.
AB  - Listening selectively to one out of several competing speakers in a "cocktail
      party" situation is a highly demanding task. It relies on a widespread cortical
      network, including auditory sensory, but also frontal and parietal brain regions
      involved in controlling auditory attention. Previous work has shown that, during
      selective listening, ongoing neural activity in auditory sensory areas is
      dominated by the attended speech stream, whereas competing input is suppressed.
      The relationship between these attentional modulations in the sensory tracking of
      the attended speech stream and frontoparietal activity during selective listening
      is, however, not understood. We studied this question in young, healthy human
      participants (both sexes) using concurrent EEG-fMRI and a sustained selective
      listening task, in which one out of two competing speech streams had to be
      attended selectively. An EEG-based speech envelope reconstruction method was
      applied to assess the strength of the cortical tracking of the to-be-attended and
      the to-be-ignored stream during selective listening. Our results show that
      individual speech envelope reconstruction accuracies obtained for the to-be
      attended speech stream were positively correlated with the amplitude of sustained
      BOLD responses in the right temporoparietal junction, a core region of the
      ventral attention network. This brain region further showed task-related
      functional connectivity to secondary auditory cortex and regions of the
      frontoparietal attention network, including the intraparietal sulcus and the
      inferior frontal gyrus. This suggests that the right temporoparietal junction is
      involved in controlling attention during selective listening, allowing for a
      better cortical tracking of the attended speech stream.SIGNIFICANCE STATEMENT
      Listening selectively to one out of several simultaneously talking speakers in a
      "cocktail party" situation is a highly demanding task. It activates a widespread
      network of auditory sensory and hierarchically higher frontoparietal brain
      regions. However, how these different processing levels interact during selective
      listening is not understood. Here, we investigated this question using fMRI and
      concurrently acquired scalp EEG. We found that activation levels in the right
      temporoparietal junction correlate with the sensory representation of a
      selectively attended speech stream. In addition, this region showed significant
      functional connectivity to both auditory sensory and other frontoparietal brain
      areas during selective listening. This suggests that the right temporoparietal
      junction contributes to controlling selective auditory attention in "cocktail
      party" situations.

PMID- 29061693
TI  - Alzheimer's disease: A matter of blood-brain barrier dysfunction?
AB  - The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells,
      and pathogens out of the brain. An early BBB breakdown and/or dysfunction have
      been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or
      brain atrophy occur. However, the role of BBB breakdown in neurodegenerative
      disorders is still not fully understood. Here, we examine BBB breakdown in animal
      models frequently used to study the pathophysiology of AD, including transgenic
      mice expressing human amyloid-beta precursor protein, presenilin 1, and tau
      mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We
      discuss the role of BBB breakdown and dysfunction in neurodegenerative process,
      pitfalls in BBB measurements, and how targeting the BBB can influence the course
      of neurological disorder. Finally, we comment on future approaches and models to
      better define, at the cellular and molecular level, the underlying mechanisms
      between BBB breakdown and neurodegeneration as a basis for developing new
      therapies for BBB repair to control neurodegeneration.

PMID- 29061699
TI  - HuD and the Survival Motor Neuron Protein Interact in Motoneurons and Are
      Essential for Motoneuron Development, Function, and mRNA Regulation.
AB  - Motoneurons establish a critical link between the CNS and muscles. If motoneurons
      do not develop correctly, they cannot form the required connections, resulting in
      movement defects or paralysis. Compromised development can also lead to
      degeneration because the motoneuron is not set up to function properly. Little is
      known, however, regarding the mechanisms that control vertebrate motoneuron
      development, particularly the later stages of axon branch and dendrite formation.
      The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of
      the survival motor neuron (SMN) protein leading to defects in vertebrate
      motoneuron development and synapse formation. Here we show using zebrafish as a
      model system that SMN interacts with the RNA binding protein (RBP) HuD in
      motoneurons in vivo during formation of axonal branches and dendrites. To
      determine the function of HuD in motoneurons, we generated zebrafish HuD mutants
      and found that they exhibited decreased motor axon branches, dramatically fewer
      dendrites, and movement defects. These same phenotypes are present in animals
      expressing low levels of SMN, indicating that both proteins function in
      motoneuron development. HuD binds and transports mRNAs and one of its target
      mRNAs, Gap43, is involved in axonal outgrowth. We found that Gap43 was decreased
      in both HuD and SMN mutants. Importantly, transgenic expression of HuD in
      motoneurons of SMN mutants rescued the motoneuron defects, the movement defects,
      and Gap43 mRNA levels. These data support that the interaction between SMN and
      HuD is critical for motoneuron development and point to a role for RBPs in
      SMA.SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal
      muscular atrophy (SMA), motor axons fail to form the normal extent of axonal
      branches and dendrites leading to decreased motor function. SMA is caused by low
      levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo
      that SMN interacts with the RNA binding protein, HuD. Novel mutants reveal that
      HuD is also necessary for motor axonal branch and dendrite formation. Data also
      revealed that both SMN and HuD affect levels of an mRNA involved in axonal
      growth. Moreover, expressing HuD in SMN-deficient motoneurons can rescue the
      motoneuron development and motor defects caused by low levels of SMN. These data
      support that SMN:HuD complexes are essential for normal motoneuron development
      and indicate that mRNA handling is a critical component of SMA.

PMID- 29061700
TI  - Development of the Visual Word Form Area Requires Visual Experience: Evidence
      from Blind Braille Readers.
AB  - Learning to read causes the development of a letter- and word-selective region
      known as the visual word form area (VWFA) within the human ventral visual object
      stream. Why does a reading-selective region develop at this anatomical location?
      According to one hypothesis, the VWFA develops at the nexus of visual inputs from
      retinotopic cortices and linguistic input from the frontotemporal language
      network because reading involves extracting linguistic information from visual
      symbols. Surprisingly, the anatomical location of the VWFA is also active when
      blind individuals read Braille by touch, suggesting that vision is not required
      for the development of the VWFA. In this study, we tested the alternative
      prediction that VWFA development is in fact influenced by visual experience. We
      predicted that in the absence of vision, the "VWFA" is incorporated into the
      frontotemporal language network and participates in high-level language
      processing. Congenitally blind (n = 10, 9 female, 1 male) and sighted control (n
      = 15, 9 female, 6 male), male and female participants each took part in two
      functional magnetic resonance imaging experiments: (1) word reading (Braille for
      blind and print for sighted participants), and (2) listening to spoken sentences
      of different grammatical complexity (both groups). We find that in blind, but not
      sighted participants, the anatomical location of the VWFA responds both to
      written words and to the grammatical complexity of spoken sentences. This
      suggests that in blindness, this region takes on high-level linguistic functions,
      becoming less selective for reading. More generally, the current findings suggest
      that experience during development has a major effect on functional
      specialization in the human cortex.SIGNIFICANCE STATEMENT The visual word form
      area (VWFA) is a region in the human cortex that becomes specialized for the
      recognition of written letters and words. Why does this particular brain region
      become specialized for reading? We tested the hypothesis that the VWFA develops
      within the ventral visual stream because reading involves extracting linguistic
      information from visual symbols. Consistent with this hypothesis, we find that in
      congenitally blind Braille readers, but not sighted readers of print, the VWFA
      region is active during grammatical processing of spoken sentences. These results
      suggest that visual experience contributes to VWFA specialization, and that
      different neural implementations of reading are possible.

PMID- 29061701
TI  - A Subconscious Interaction between Fixation and Anticipatory Pursuit.
AB  - Ocular smooth pursuit and fixation are typically viewed as separate systems, yet
      there is evidence that the brainstem fixation system inhibits pursuit. Here we
      present behavioral evidence that the fixation system modulates pursuit behavior
      outside of conscious awareness. Human observers (male and female) either pursued
      a small spot that translated across a screen, or fixated it as it remained
      stationary. As shown previously, pursuit trials potentiated the oculomotor
      system, producing anticipatory eye velocity on the next trial before the target
      moved that mimicked the stimulus-driven velocity. Randomly interleaving fixation
      trials reduced anticipatory pursuit, suggesting that a potentiated fixation
      system interacted with pursuit to suppress eye velocity in upcoming pursuit
      trials. The reduction was not due to passive decay of the potentiated pursuit
      signal because interleaving "blank" trials in which no target appeared did not
      reduce anticipatory pursuit. Interspersed short fixation trials reduced
      anticipation on long pursuit trials, suggesting that fixation potentiation was
      stronger than pursuit potentiation. Furthermore, adding more pursuit trials to a
      block did not restore anticipatory pursuit, suggesting that fixation potentiation
      was not overridden by certainty of an imminent pursuit trial but rather was
      immune to conscious intervention. To directly test whether cognition can override
      fixation suppression, we alternated pursuit and fixation trials to perfectly
      specify trial identity. Still, anticipatory pursuit did not rise above that
      observed with an equal number of random fixation trials. The results suggest that
      potentiated fixation circuitry interacts with pursuit circuitry at a subconscious
      level to inhibit pursuit.SIGNIFICANCE STATEMENT When an object moves, we view it
      with smooth pursuit eye movements. When an object is stationary, we view it with
      fixational eye movements. Pursuit and fixation are historically regarded as
      controlled by different neural circuitry, and alternating between invoking them
      is thought to be guided by a conscious decision. However, our results show that
      pursuit is actively suppressed by prior fixation of a stationary object. This
      suppression is involuntary, and cannot be avoided even if observers are certain
      that the object will move. The results suggest that the neural fixation circuitry
      is potentiated by engaging stationary objects, and interacts with pursuit outside
      of conscious awareness.

PMID- 29061703
TI  - Baseline Levels of Rapid Eye Movement Sleep May Protect Against Excessive
      Activity in Fear-Related Neural Circuitry.
AB  - Sleep, and particularly rapid eye movement sleep (REM), has been implicated in
      the modulation of neural activity following fear conditioning and extinction in
      both human and animal studies. It has long been presumed that such effects play a
      role in the formation and persistence of posttraumatic stress disorder, of which
      sleep impairments are a core feature. However, to date, few studies have
      thoroughly examined the potential effects of sleep prior to conditioning on
      subsequent acquisition of fear learning in humans. Furthermore, these studies
      have been restricted to analyzing the effects of a single night of sleep-thus
      assuming a state-like relationship between the two. In the current study, we used
      long-term mobile sleep monitoring and functional neuroimaging (fMRI) to explore
      whether trait-like variations in sleep patterns, measured in advance in both male
      and female participants, predict subsequent patterns of neural activity during
      fear learning. Our results indicate that higher baseline levels of REM sleep
      predict reduced fear-related activity in, and connectivity between, the
      hippocampus, amygdala and ventromedial PFC during conditioning. Additionally,
      skin conductance responses (SCRs) were weakly correlated to the activity in the
      amygdala. Conversely, there was no direct correlation between REM sleep and SCRs,
      indicating that REM may only modulate fear acquisition indirectly. In a follow-up
      experiment, we show that these results are replicable, though to a lesser extent,
      when measuring sleep over a single night just before conditioning. As such,
      baseline sleep parameters may be able to serve as biomarkers for resilience, or
      lack thereof, to trauma.SIGNIFICANCE STATEMENT Numerous studies over the past two
      decades have established a clear role of sleep in fear-learning processes.
      However, previous work has focused on the effects of sleep following fear
      acquisition, thus neglecting the potential effects of baseline sleep levels on
      the acquisition itself. The current study provides the first evidence in humans
      of such an effect. Specifically, the results of this study suggest that baseline
      rapid eye movement (REM) sleep may serve a protective function against enhanced
      fear encoding through the modulation of connectivity between the hippocampus,
      amygdala, and the ventromedial PFC. Building on this finding, baseline REM
      measurements may serve as a noninvasive biomarker for resilience to trauma or,
      conversely, to the potential development of posttraumatic stress disorder
      following trauma.

PMID- 29061702
TI  - Presynaptic Neuronal Nicotinic Receptors Differentially Shape Select Inputs to
      Auditory Thalamus and Are Negatively Impacted by Aging.
AB  - Acetylcholine (ACh) is a potent neuromodulator capable of modifying patterns of
      acoustic information flow. In auditory cortex, cholinergic systems have been
      shown to increase salience/gain while suppressing extraneous information.
      However, the mechanism by which cholinergic circuits shape signal processing in
      the auditory thalamus (medial geniculate body, MGB) is poorly understood. The
      present study, in male Fischer Brown Norway rats, seeks to determine the location
      and function of presynaptic neuronal nicotinic ACh receptors (nAChRs) at the
      major inputs to MGB and characterize how nAChRs change during aging. In vitro
      electrophysiological/optogenetic methods were used to examine responses of MGB
      neurons after activation of nAChRs during a paired-pulse paradigm. Presynaptic
      nAChR activation increased responses evoked by stimulation of excitatory
      corticothalamic and inhibitory tectothalamic terminals. Conversely, nAChR
      activation appeared to have little effect on evoked responses from inhibitory
      thalamic reticular nucleus and excitatory tectothalamic terminals. In situ
      hybridization data showed nAChR subunit transcripts in GABAergic inferior
      colliculus neurons and glutamatergic auditory cortical neurons supporting the
      present slice findings. Responses to nAChR activation at excitatory
      corticothalamic and inhibitory tectothalamic inputs were diminished by aging.
      These findings suggest that cholinergic input to the MGB increases the strength
      of tectothalamic inhibitory projections, potentially improving the signal-to
      noise ratio and signal detection while increasing corticothalamic gain, which may
      facilitate top-down identification of stimulus identity. These mechanisms appear
      to be affected negatively by aging, potentially diminishing speech perception in
      noisy environments. Cholinergic inputs to the MGB appear to maximize sensory
      processing by adjusting both top-down and bottom-up mechanisms in conditions of
      attention and arousal.SIGNIFICANCE STATEMENT The pedunculopontine tegmental
      nucleus is the source of cholinergic innervation for sensory thalamus and is a
      critical part of an ascending arousal system that controls the firing mode of
      thalamic cells based on attentional demand. The present study describes the
      location and impact of aging on presynaptic neuronal nicotinic acetylcholine
      receptors (nAChRs) within the circuitry of the auditory thalamus (medial
      geniculate body, MGB). We show that nAChRs are located on ascending inhibitory
      and descending excitatory presynaptic inputs onto MGB neurons, likely increasing
      gain selectively and improving temporal clarity. In addition, we show that aging
      has a deleterious effect on nAChR efficacy. Cholinergic dysfunction at the level
      of MGB may affect speech understanding negatively in the elderly population.

PMID- 29061704
TI  - A Naturally Occurring Deletion in FliE from Salmonella enterica Serovar Dublin
      Results in an Aflagellate Phenotype and Defective Proinflammatory Properties.
AB  - Salmonella enterica serovar Dublin is adapted to cattle but is able to infect
      humans with high invasiveness. An acute inflammatory response at the intestine
      helps to prevent Salmonella dissemination to systemic sites. Flagella contribute
      to this response by providing motility and FliC-mediated signaling through
      pattern recognition receptors. In a previous work, we reported a high frequency
      (11 out of 25) of S Dublin isolates lacking flagella in a collection obtained
      from humans and cattle. The aflagellate strains were impaired in their
      proinflammatory properties in vitro and in vivo The aim of this work was to
      elucidate the underlying cause of the absence of flagella in S Dublin isolates.
      We report here that class 3 flagellar genes are repressed in the human
      aflagellate isolates, due to impaired secretion of FliA anti-sigma factor FlgM.
      This phenotype is due to an in-frame 42-nucleotide deletion in the fliE gene,
      which codes for a protein located in the flagellar basal body. The deletion is
      predicted to produce a protein lacking amino acids 18 to 31. The aflagellate
      phenotype was highly stable; revertants were obtained only when fliA was
      artificially overexpressed combined with several successive passages in motility
      agar. DNA sequence analysis revealed that motile revertants resulted from
      duplications of DNA sequences in fliE adjacent to the deleted region. These
      duplications produced a FliE protein of similar length to the wild type and
      demonstrate that amino acids 18 to 31 of FliE are not essential. The same
      deletion was detected in S Dublin isolates obtained from cattle, indicating that
      this mutation circulates in nature.

PMID- 29061705
TI  - Polyphenol- and Caffeine-Rich Postfermented Pu-erh Tea Improves Diet-Induced
      Metabolic Syndrome by Remodeling Intestinal Homeostasis in Mice.
AB  - Postfermented Pu-erh tea (PE) protects against metabolic syndrome (MS), but
      little is known regarding its underlying mechanisms. Animal experiments were
      performed to determine whether the gut microbiota mediated the improvement in
      diet-induced MS by PE and its main active components (PEAC). We confirmed that PE
      altered the body composition and energy efficiency, attenuated metabolic
      endotoxemia and systemic and multiple-tissue inflammation, and improved the
      glucose and lipid metabolism disorder in high-fat diet (HFD)-fed mice via
      multiple pathways. Notably, PE promoted the lipid oxidation and browning of white
      adipose tissue (WAT) in HFD-fed mice. Polyphenols and caffeine (CAF) played
      critical roles in improving these parameters. Meanwhile, PE remodeled the
      disrupted intestinal homeostasis that was induced by the HFD. Many metabolic
      changes observed in the mice were significantly correlated with alterations in
      specific gut bacteria. Akkermansia muciniphila and Faecalibacterium prausnitzii
      were speculated to be the key gut bacterial links between the PEAC treatment and
      MS at the genus and species levels. Interestingly, A. muciniphila administration
      altered body composition and energy efficiency, promoted the browning of WAT, and
      improved the lipid and glucose metabolism disorder in the HFD-fed mice, whereas
      F. prausnitzii administration reduced the HFD-induced liver and intestinal
      inflammatory responses. In summary, polyphenol- and CAF-rich PE improved diet
      induced MS, and this effect was associated with a remodeling of the gut
      microbiota.

PMID- 29061707
TI  - Cell invasion and pyruvate oxidase derived H2O2 are critical for Streptococcus
      pneumoniae mediated cardiomyocyte killing.
AB  - Streptococcus pneumoniae (Spn, the pneumococcus) is the leading cause of
      community-acquired pneumonia and is now recognized to be a direct contributor to
      adverse acute cardiac events. During invasive pneumococcal disease, Spn can gain
      access to the myocardium, kill cardiomyocytes, and form bacteria-filled
      "microlesions" causing considerable acute and long-lasting cardiac damage. While
      the molecular mechanisms responsible for bacterial translocation into the heart
      have been elucidated, the initial interactions of heart-invaded Spn with
      cardiomyocytes remain unclear. Herein, we used a low multiplicity of Spn
      infection model with HL-1 mouse cardiomyocytes to investigate these early events.
      Using adhesion/invasion assays, immunofluorescent and transmission electron
      microscopy, we show that Spn rapidly adhered to and invaded cardiomyocytes. What
      is more, pneumococci existed as intra-vacuolar bacteria or escaped into the
      cytoplasm. Pulse-chase assays with BrdU confirmed intracellular replication of
      pneumococci within HL-1 cells. Using endocytosis inhibitors, bacterial isogenic
      mutants, and neutralizing antibodies against host proteins recognized by Spn
      adhesins, we show that Spn uptake by cardiomyocytes is not through the well
      studied canonical interactions identified for vascular endothelial cells. Indeed,
      Spn invasion of HL-1 cells occurred through clathrin-mediated endocytosis (CME)
      and independently of Choline binding protein A (CbpA)/Laminin receptor,
      CbpA/Polymeric immunoglobulin receptor, or cell wall phosphorylcholine/Platelet
      activating factor receptor. Subsequently, we determined that pneumolysin and
      streptococcal pyruvate oxidase derived H2O2 production were required for
      cardiomyocyte killing. Finally, we show that this cytotoxicity could be abrogated
      using CME inhibitors or antioxidants attesting intracellular replication of Spn
      as a key first step in pneumococcal pathogenesis within the heart.

PMID- 29061706
TI  - NLRP3 Is a Critical Regulator of Inflammation and Innate Immune Cell Response
      during Mycoplasma pneumoniae Infection.
AB  - Mycoplasma pneumoniae is an atypical bacterial respiratory pathogen known to
      cause a range of airway inflammation and lung and extrapulmonary pathologies. We
      recently reported that an M. pneumoniae-derived ADP-ribosylating and vacuolating
      toxin called community-acquired respiratory distress syndrome (CARDS) toxin is
      capable of triggering NLRP3 (NLR-family, leucine-rich repeat protein 3)
      inflammasome activation and interleukin-1beta (IL-1beta) secretion in
      macrophages. However, it is unclear whether the NLRP3 inflammasome is important
      for the immune response during M. pneumoniae acute infection. In the current
      study, we utilized in vitro and in vivo models of M. pneumoniae infection to
      characterize the role of the NLRP3 inflammasome during acute infection. M.
      pneumoniae-infected macrophages deficient for inflammasome components NLRP3, ASC
      (apoptosis speck-like protein containing a caspase activation and recruitment
      domain), or caspase-1 failed to process and secrete IL-1beta. The MyD88/NF-kappaB
      signaling pathway was found to be critical for proinflammatory gene expression in
      macrophages infected with M. pneumoniae C57BL/6 mice deficient for NLRP3
      expression were unable to produce IL-1beta in the airways during acute infection,
      and lack of this inflammatory response led to deficient immune cell activation
      and delayed bacterial clearance. These findings are the first to report the
      importance of the NLRP3 inflammasome in regulating the inflammatory response and
      influencing the progression of M. pneumoniae during acute infection.

PMID- 29061708
TI  - Leishmania-derived trimannose modulates inflammatory response to significantly
      reduce Leishmania (L.) major-induced lesions.
AB  - Leishmania lipophosphoglycan (LPG) is a key virulence factor, initiating
      inflammation resulting in cutaneous lesions. LPG is capped by various
      oligosaccharides. How these glycans are recognized and how they alter the course
      of Leishmania infection is poorly understood. Previous studies synthesized alpha
      1,2-trimannose cap sugars on latex beads demonstrated that C57BL/6 mice co
      inoculated with L. major and trimannose-coated beads produced significantly
      higher levels of IL-12 p40 and other pro-inflammatory, type 1 cytokines compared
      L. major infection alone within the first 48 h of infection. However, as L. major
      infection typically progress over weeks to months, the role of trimannose in
      altering disease progression over the course of infection was unknown. Wild-type
      mice were inoculated with either trimannose or carrier (uncoated) beads, infected
      with L. major alone, co-inoculated with carrier beads and L. major, or co
      inoculated with trimannose beads and L. major Trimannose treatment of L. major
      infected mice decreased parasite load and significantly decreased lesion size at
      14 days post infection (pi) compared to non-treated, infected mice. Infected,
      trimannose-treated mice had decreased IL-12p40 and IL-10 secretion and increased
      IFN-gamma at 14 days pi. Mice lacking the ability to detect trimannose, mannose
      receptor deleted mice (MR-/-), when treated with trimannose beads and infected
      with L. major did not have decreased lesion size. Leishmania-derived trimannose
      represents a novel immunomodulator that provides early type 1-skewed cytokine
      production to control parasite load and alter the course of cutaneous
      leishmaniasis.

PMID- 29061709
TI  - Genomic and Transcriptomic Analysis of Escherichia coli Strains Associated with
      Persistent and Transient Bovine Mastitis and the Role of Colanic Acid.
AB  - Escherichia coli is a leading cause of bacterial mastitis in dairy cattle. It is
      most often transient in nature, causing an infection that lasts 2 to 3 days.
      However, E. coli has been shown to cause a persistent infection in a minority of
      cases. Mechanisms that allow for a persistent E. coli infection are not fully
      understood. The goal of this work was to determine differences between E. coli
      strains originally isolated from dairy cattle with transient and persistent
      mastitis. Using RNA sequencing, we show gene expression differences in nearly 200
      genes when bacteria from the two clinical phenotypes are compared. We sequenced
      the genomes of the E. coli strains and report genes unique to the two phenotypes.
      Differences in the wca operon, which encodes colanic acid, were identified by DNA
      as well as RNA sequencing and differentiated the two phenotypes. Previous work
      demonstrated that E. coli strains that cause persistent infections were more
      motile than those that cause transient infections. Deletion of genes in the wca
      operon from a persistent-infection strain resulted in a reduction of motility as
      measured in swimming and swarming assays. Furthermore, colanic acid has been
      shown to protect bacteria from complement-mediated killing. We show that
      transient-infection E. coli strains were more sensitive to complement-mediated
      killing. The deletion of genes from the wca operon caused a persistent-infection
      E. coli strain to become sensitive to complement-mediated killing. This work
      identifies important differences between E. coli strains that cause persistent
      and transient mammary infections in dairy cattle.

PMID- 29061711
TI  - Stacking the Deck: Studies of Patients with Multiple Autoimmune Diseases
      Propelled Our Understanding of Type 1 Diabetes as an Autoimmune Disease.

PMID- 29061710
TI  - Heparinase Is Essential for Pseudomonas aeruginosa Virulence during Thermal
      Injury and Infection.
AB  - The opportunistic pathogen Pseudomonas aeruginosa is a major cause of sepsis in
      severely burned patients. If it is not eradicated from the wound, it translocates
      to the bloodstream, causing sepsis, multiorgan failure, and death. We recently
      described the P. aeruginosa heparinase-encoding gene, hepP, whose expression was
      significantly enhanced when P. aeruginosa strain UCBPP_PA14 (PA14) was grown in
      whole blood from severely burned patients. Further analysis demonstrated that
      hepP contributed to the in vivo virulence of PA14 in the Caenorhabditis elegans
      model. In this study, we utilized the murine model of thermal injury to examine
      the contribution of hepP to the pathogenesis of P. aeruginosa during burn wound
      infection. Mutation of hepP reduced the rate of mortality from 100% for mice
      infected with PA14 to 7% for mice infected with PA14::hepP While comparable
      numbers of PA14 and PA14::hepP bacteria were recovered from infected skin, only
      PA14 was recovered from the livers and spleens of infected mice. Despite its
      inability to spread systemically, PA14::hepP formed perivascular cuffs around the
      blood vessels within the skin of the thermally injured/infected mice.
      Intraperitoneal inoculation of the thermally injured mice, bypassing the need for
      translocation, produced similar results. The rate of mortality for mice infected
      with PA14::hepP was 0%, whereas it was 66% for mice infected with PA14. As
      before, only PA14 was recovered from the livers and spleens of infected mice.
      These results suggest that hepP plays a crucial role in the pathogenesis of PA14
      during burn wound infection, most likely by contributing to PA14 survival in the
      bloodstream of the thermally injured mouse during sepsis.

PMID- 29061712
TI  - Pillars Article: Islet-cell Antibodies in Diabetes Mellitus with Autoimmune
      Polyendocrine Deficiencies. Lancet. 1974. 304: 1279-1283.

PMID- 29061713
TI  - Pillars Article: Antibodies to Pancreatic Islet Cells in Insulin-dependent
      Diabetics with Coexistent Autoimmune Disease. Lancet. 1974. 304: 1529-1531.

PMID- 29061714
TI  - Correction: IL-33 Signaling Regulates Innate IL-17A and IL-22 Production via
      Suppression of Prostaglandin E2 during Lung Fungal Infection.

PMID- 29061715
TI  - Statin initiations and QRISK2 scoring in UK general practice: a THIN database
      study.
AB  - BACKGROUND: Statin prescribing should be based on cardiovascular disease (CVD)
      risk, but evidence suggests overtreatment of low-risk groups and undertreatment
      of high-risk groups. AIM: To investigate the relationship between CVD risk
      scoring in primary care and initiation of statins for the primary prevention of
      CVD, and the effect of changes to the National Institute for Health and Care
      Excellence (NICE) guidance in 2014. DESIGN AND SETTING: Historical cohort study
      using UK electronic primary care records. METHOD: A cohort was created of statin
      naive patients without CVD between 1 January 2000 and 31 December 2015. CVD risk
      scores (calculated using QRISK2 available from 2012) and statin initiations were
      identified. Rates of CVD risk score recording were calculated and relationships
      between CVD risk category (low-, intermediate-, and high-risk: <10%, 10-19.9%,
      and >=20% 10-year CVD risk) and statin initiation were analysed. RESULTS: A total
      of 1.4 million patients were identified from 248 practices. Of these, 151 788 had
      a recorded CVD risk score since 2012 (10.67%) and 217 860 were initiated on a
      statin (15.31%). Among patients initiated on a statin after 2012, 27.1% had a
      documented QRISK2 score: 2.7% of low-risk, 13.8% of intermediate-risk, and 35.0%
      of high-risk patients were initiated on statins. Statin initiation rates halved
      from a peak in 2006. After the 2014 NICE guidelines, statin initiation rates
      declined in high-risk patients but increased in intermediate-risk patients.
      CONCLUSION: Most patients initiated on statins had no QRISK2 score recorded. Most
      patients at high risk of CVD were not initiated on statins. One in six statin
      initiations were to low-risk patients indicating significant overtreatment.
      Initiations of statins in intermediate-risk patients rose after NICE guidelines
      were updated in 2014.

PMID- 29061717
TI  - Identifying people with a learning disability: an advanced search for general
      practice.
AB  - BACKGROUND: People with learning disabilities (LD) have poor physical and mental
      health when compared with the general population. They are also likely to find it
      more difficult than others to describe their symptoms adequately. It is therefore
      harder for healthcare workers to identify the health needs of those with learning
      disabilities, with the danger of some problems being left unrecognised. Practice
      registers record only a proportion of those who are eligible, making it difficult
      to target improvements in their health care. AIM: To test a Read Code search
      supporting the identification of people with a mild-to-moderate learning
      disability who are not currently on the learning disability register. DESIGN AND
      SETTING: An observational study in primary care in West Yorkshire. METHOD: Read
      Code searches were created to identify individuals with a learning disability not
      on the LD register; they were field tested and further refined before testing in
      general practice. RESULTS: Diagnostic codes identified small numbers of
      individuals who should have been on the LD register. Functional and service use
      codes often created large numbers of false-positive results. The specific
      descriptive codes 'Learning difficulties' and 'Referral to learning disability
      team' needed follow-up review, and then identified some individuals with LD who
      were not on the register. CONCLUSION: The Read Code search supported practices to
      populate their registers and was quick to run and review, making it a viable
      choice to support register revalidation. However, it did not find large numbers
      of people eligible for the LD register who were previously unidentified by their
      practice, suggesting that additional complementary methods are required to
      support practices to validate their registers.

PMID- 29061718
TI  - Inhibition of Aneurysm Progression by Direct Renin Inhibition in a Rabbit Model.
AB  - Angiotensin II is thought to participate in aneurysm formation, because of its
      ability to induce and perpetuate inflammation in the aortic wall. Because
      activation of renin is the first step of the renin-angiotensin system, renin
      inhibition could inhibit all components of this system effectively. Therefore, we
      examined the hypothesis that direct inhibition of renin activity could decrease
      the expansion of aortic aneurysm using a rabbit model. Aortic dilatation was
      induced by incubation with elastase around the rabbit abdominal aorta. Continuous
      administration of a direct renin inhibitor, aliskiren, was started at 1 week
      before incubation with elastase and continued for 5 weeks. Treatment with
      aliskiren markedly inhibited tissue renin activation and resulted in a
      significant reduction in angiotensin I and II production in the aneurysm wall.
      Consequently, the inhibition of renin activity prevented the expansion of
      experimental aortic aneurysm associated with preservation of the medial layer,
      independent of its blood pressure-lowering effect. Administration of aliskiren
      led to the inhibition of activation of NF-kappaB (nuclear factor-kappaB), AP-1
      (activator protein-1), and CREB (cAMP response element-binding protein), which
      are thought to cooperatively regulate the inflammatory gene expression profile
      associated with aneurysm formation. As a result, treatment with aliskiren
      inhibited macrophage accumulation through suppression of MCP-1 (monocyte
      chemoattractant protein-1) and CCL4 (C-C motif chemokine ligand 4) expression,
      and TNF-alpha (tumor necrosis factor-alpha) production and activation of MMP-2
      (matrix metalloproteinase-2) and MMP-9 (matrix metalloproteinase-9) were also
      suppressed in the aneurysm wall. In addition, inhibition of (pro)renin receptor
      elevation was also observed after treatment with aliskiren. Direct inhibition of
      renin activity using aliskiren prevented the progression of aortic aneurysm,
      suggesting it as a therapeutic option to treat abdominal aortic aneurysm.

PMID- 29061719
TI  - Mineralocorticoid Receptor-Dependent Adverse Remodeling After Myocardial
      Infarction Mediated by uNGALant Activation of NFkappaB.

PMID- 29061716
TI  - GPs' experiences of children with anxiety disorders in primary care: a
      qualitative study.
AB  - BACKGROUND: Anxiety disorders have a median age of onset of 11 years and are the
      most common emotional disorders in childhood; however, a significant proportion
      of those affected do not access professional support. In the UK, GPs are often
      the first medical professional that families see so are in a prime position to
      support children with anxiety disorders; however, currently there is little
      research available on GPs' perspectives on and experiences of supporting children
      with these disorders. AIM: To explore the experiences of GPs in relation to
      identification, management, and access to specialist services for children (<12
      years) with anxiety disorders. DESIGN AND SETTING: Twenty semi-structured
      interviews were conducted with GPs in primary care throughout England. METHOD:
      GPs reflected a diverse group in relation to the ethnic and socioeconomic profile
      of registered patients, GP age, sex, professional status, previous engagement
      with research, and practice size and location. Purposive sampling was used to
      recruit GPs until theoretical saturation was reached. Data were analysed using a
      constant comparative method of thematic analysis. RESULTS: Data from 20 semi
      structured interviews were organised into three themes: decision making,
      responsibility, and emotional response, with an overarching theme of GPs feeling
      ill equipped. These themes were retrospectively analysed to illustrate their role
      at different stages in the primary care process (identification, management, and
      access to specialist services). CONCLUSION: GPs feel ill equipped to manage and
      support childhood anxiety disorders, demonstrating a need for medical training to
      include greater emphasis on children's mental health, as well as potential for
      greater collaboration between primary and specialist services.

PMID- 29061721
TI  - Hypertension on the ROX: Durable Blood Pressure Lowering With Central Iliac
      Arteriovenous Anastomosis.

PMID- 29061722
TI  - Longitudinal Blood Pressure in Late-Stage Chronic Kidney Disease and the Risk of
      End-Stage Kidney Disease or Mortality (Best Blood Pressure in Chronic Kidney
      Disease Study).
AB  - Whether different methods of quantitating blood pressure (BP) in late chronic
      kidney disease better mimic pathophysiological processes and clinical outcomes
      remains unclear. In a retrospective study, we determined the association of BP
      with end-stage kidney disease (ESKD) and all-cause mortality with BP modeled at
      baseline versus longitudinally with time-varying Cox models as (1) current (most
      recent) clinic visit, (2) lag (visit immediately preceding the current), (3)
      cumulative (average of previous measurements), and (4) change from baseline to
      the most recent. Among 1203 (6913 visits) study patients, the mean age and
      baseline estimated glomerular filtration rate were 66 and 18 mL.min-1.1.73 m-2),
      and 40% were female. Patients had a mean of 6.7 BP measurements, 540 (44.8%)
      reached ESKD, and 141 (11.7%) died. For systolic BP >160, current (hazard ratio
      [HR], 1.67), cumulative (HR, 1.58), and a rise to >160 from baseline 120 to 160
      (HR, 1.60) were associated with ESKD. Similarly, diastolic BP >85 was associated
      with ESKD when modeled as current (HR, 1.47), lag (HR, 1.63), cumulative (HR,
      2.15), or change from baseline (rise to >85 from a baseline of 60-85; HR, 1.62).
      Both low SBP (<120), when modeled as current (HR, 1.59), cumulative exposure (HR,
      1.76), persistently <120 (HR, 2.28), and high SBP (>140), when modeled as
      cumulative exposure, were associated with all-cause mortality. For diastolic BP,
      only cumulative >85 was significantly associated with mortality (HR, 2.75). Thus,
      in late-stage chronic kidney disease, persistently high or rises in systolic BP
      or diastolic BP are associated with risk of ESKD, whereas baseline BP measures
      did not convey information on risk.

PMID- 29061723
TI  - Maternal Vascular Physiology in Preeclampsia.

PMID- 29061724
TI  - Is 24-Hour Central Blood Pressure Superior to 24-Hour Brachial Blood Pressure for
      Predicting Organ Damage?

PMID- 29061720
TI  - Role of Kidneys in Sex Differences in Angiotensin II-Induced Hypertension.
AB  - The significance of kidneys in regulation of sodium and water balance and
      hemodynamics has been demonstrated both in patients and animal models. In the
      present study, we tested our hypothesis that kidneys play an essential role in
      control of sex differences in angiotensin II (Ang II)-dependent hypertension.
      Kidney transplantations (KTXs) were performed between male (M) and female (F)
      C57BL/6 mice (donor->recipient: F->F, M->M, F->M, and M->F). Radiotelemetry
      transmitters were implanted for measurement of mean arterial pressure during the
      infusion of Ang II (600 ng.kg-1.min-1). Gene expressions and inflammatory
      responses in the transplanted grafts were assessed. We found that same-sex-KTX
      mice still exhibited sex differences in Ang II-dependent hypertension (31.3+/-0.8
      mm Hg in M->M versus 12.2+/-0.6 mm Hg in F->F), which were reduced between males
      and females when they received kidneys of the opposite sex (32.9+/-1 mm Hg in M
      >F versus 22.3+/-0.7 mm Hg in F->M). The sex differences in gene expressions,
      including AT1R (angiotensin II receptor, type 1), AT1R/AT2R, ET-1 (endothelin-1),
      ETA (endothelin receptor type A), NHE3 (sodium-hydrogen exchanger 3), alpha-ENaC
      (alpha-epithelial sodium channel), and gamma-ENaC, were unaltered in same-sex
      KTXs and much lessened in cross-sex KTXs. In addition, the cross-sex KTXs
      exhibited more robust inflammatory responses reflected by higher expression of IL
      6 (interleukin 6), TNFalpha (tumor necrosis factor alpha), and KC (keratinocyte
      derived chemokine) than same-sex KTX. Our results indicate that kidneys play an
      essential role in sex differences of Ang II-dependent hypertension. KTX of male
      kidneys to females augmented the blood pressure response, whereas KTX of female
      kidneys to males attenuated the blood pressure response. The host's extrarenal
      systems modulate expressions of many genes and inflammatory response, which may
      also contribute to the sex differences in blood pressure regulation.

PMID- 29061725
TI  - Relationship Between 24-Hour Ambulatory Central Systolic Blood Pressure and Left
      Ventricular Mass: A Prospective Multicenter Study.
AB  - : We investigated the relationship between left ventricular mass and brachial
      office as well as brachial and central ambulatory systolic blood pressure in 7
      European centers. Central systolic pressure was measured with a validated
      oscillometric device, using a transfer function, and mean/diastolic pressure
      calibration. M-mode images were obtained by echocardiography, and left
      ventricular mass was determined by one single reader blinded to blood pressure.
      We studied 289 participants (137 women) free from antihypertensive drugs (mean
      age: 50.8 years). Mean office blood pressure was 145/88 mm Hg and mean brachial
      and central ambulatory systolic pressures were 127 and 128 mm Hg, respectively.
      Mean left ventricular mass was 93.3 kg/m2, and 25.6% had left ventricular
      hypertrophy. The correlation coefficient between left ventricular mass and
      brachial office, brachial ambulatory, and central ambulatory systolic pressure
      was 0.29, 0.41, and 0.47, respectively (P=0.003 for comparison between brachial
      office and central ambulatory systolic pressure and 0.32 for comparison between
      brachial and central ambulatory systolic pressure). The results were consistent
      for men and women, and young and old participants. The areas under the curve for
      prediction of left ventricular hypertrophy were 0.618, 0.635, and 0.666 for
      brachial office, brachial, and central ambulatory systolic pressure, respectively
      (P=0.03 for comparison between brachial and central ambulatory systolic
      pressure). In younger participants, central ambulatory systolic pressure was
      superior to both other measurements. Central ambulatory systolic pressure,
      measured with an oscillometric cuff, shows a strong trend toward a closer
      association with left ventricular mass and hypertrophy than brachial
      office/ambulatory systolic pressure. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT01278732.

PMID- 29061726
TI  - Angiotensin II Type 1 Receptor Mechanoactivation Involves RGS5 (Regulator of G
      Protein Signaling 5) in Skeletal Muscle Arteries: Impaired Trafficking of RGS5 in
      Hypertension.
AB  - Studies suggest that arteriolar pressure-induced vasoconstriction can be
      initiated by GPCRs (G protein-coupled receptors), including the AT1R (angiotensin
      II type 1 receptor). This raises the question, are such mechanisms regulated by
      negative feedback? The present studies examined whether RGS (regulators of G
      protein signaling) proteins in vascular smooth muscle cells are colocalized with
      the AT1R when activated by mechanical stress or angiotensin II and whether this
      modulates AT1R-mediated vasoconstriction. To determine whether activation of the
      AT1R recruits RGS5, an in situ proximity ligation assay was performed in primary
      cultures of cremaster muscle arteriolar vascular smooth muscle cells treated with
      angiotensin II or hypotonic solution in the absence or presence of candesartan
      (an AT1R blocker). Proximity ligation assay results revealed a concentration
      dependent increase in trafficking/translocation of RGS5 toward the activated
      AT1R, which was attenuated by candesartan. In intact arterioles, knockdown of
      RGS5 enhanced constriction to angiotensin II and augmented myogenic responses to
      increased intraluminal pressure. Myogenic constriction was attenuated to a higher
      degree by candesartan in RGS5 siRNA-transfected arterioles, consistent with RGS5
      contributing to downregulation of AT1R-mediated signaling. Further, translocation
      of RGS5 was impaired in vascular smooth muscle cells of spontaneously
      hypertensive rats. This is consistent with dysregulated (RGS5-mediated) AT1R
      signaling that could contribute to excessive vasoconstriction in hypertension. In
      intact vessels, candesartan reduced myogenic vasoconstriction to a greater extent
      in spontaneously hypertensive rats compared with controls. Collectively, these
      findings suggest that AT1R activation results in translocation of RGS5 toward the
      plasma membrane, limiting AT1R-mediated vasoconstriction through its role in
      Gq/11 protein-dependent signaling.

PMID- 29061727
TI  - Aldosterone Target NGAL (Neutrophil Gelatinase-Associated Lipocalin) Is Involved
      in Cardiac Remodeling After Myocardial Infarction Through NFkappaB Pathway.
AB  - Myocardial infarction (MI) is accompanied by cardiac fibrosis, which contributes
      to cardiac dysfunction. Mineralocorticoid receptor (MR) antagonists have
      beneficial effects in patients with left ventricular (LV) dysfunction after MI.
      We herein investigated the role of the MR target NGAL (neutrophil gelatinase
      associated lipocalin) in post-MI cardiac damages. Both higher baseline NGAL and a
      greater increase in serum NGAL levels during follow-up were significantly
      associated with lower 6-month LV ejection fraction recovery in a cohort of 119
      post-MI patients, as assessed by cardiac magnetic resonance imaging. NGAL protein
      levels increased in the LV at 7 days post-MI in wild-type mice with MI. This
      effect was prevented by treatment with the nonsteroidal MR antagonist finerenone
      (1 mg/kg per day). NGAL knockout mice with MI had lower LV interstitial fibrosis
      and inflammation, better LV contractility and compliance, and greater stroke
      volume and cardiac output than wild-type mice with MI at 3 months post-MI.
      Aldosterone (10-8 mol/L) increased NGAL expression in cultured human cardiac
      fibroblasts. Cells treated with aldosterone or NGAL (500 ng/mL) showed increased
      production of collagen type I. The effects of aldosterone were abolished by
      finerenone (10-6 mol/L) or NGAL knockdown. This NGAL-mediated activity relied on
      NFkappaB (nuclear factor-kappaB) activation, confirmed by the use of the NFkappaB
      specific inhibitor BAY11-7082, which prevented the effect of both aldosterone and
      NGAL on collagen type I production. In conclusion, NGAL, a downstream MR
      activation target, is a key mediator of post-MI cardiac damage. NGAL may be a
      potential therapeutic target in cardiovascular pathological situations in which
      MR is involved.

PMID- 29061730
TI  - Speed dating for doctors: getting skilled refugees into NHS practice.

PMID- 29061728
TI  - Central Iliac Arteriovenous Anastomosis for Uncontrolled Hypertension: One-Year
      Results From the ROX CONTROL HTN Trial.
AB  - : Creation of a central iliac arteriovenous anastomosis using a novel nitinol
      coupler device results in an immediate, significant reduction of blood pressure
      (BP). We present efficacy and safety findings at 12 months post-coupler
      insertion. This open-label, multicenter, prospective, randomized trial enrolled
      patients with a baseline office systolic BP >=140 mm Hg and average daytime
      ambulatory BP >=135/85 mm Hg. Subjects were randomly allocated to coupler
      implantation and continuing previous pharmacotherapy or to maintain previous
      treatment alone. At 12 months, 39 patients who had coupler therapy were included
      in the intention-to-treat analysis. Office-based systolic BP reduced by 25.1+/
      23.3 mm Hg (baseline, 174+/-18 mm Hg; P<0.0001) post-coupler placement, and
      office diastolic BP reduced by 20.8+/-13.3 mm Hg (baseline, 100+/-13 mm Hg;
      P<0.0001). Mean 24-hour ambulatory BP reduced by 12.6+/-17.4/15.3+/-9.7 mm Hg
      (P<0.0001 for both). In a prespecified subset of patients who failed to respond
      adequately to prior renal denervation, coupler therapy led to highly significant
      reduction in office systolic/diastolic BP (30.7/24.1 mm Hg) and significant
      reduction in 24-hour ambulatory systolic/diastolic BP (12.4/14.4 mm Hg) at 12
      months (n=9). After coupler therapy, 14 patients (33%) developed ipsilateral
      venous stenosis; all were treated successfully with venous stenting. These
      findings confirm the importance of arterial mechanics in the pathophysiology of
      hypertension and support the clinical use of a central iliac arteriovenous
      anastomosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT01642498.

PMID- 29061731
TI  - Ubiquitin-Specific Protease USP6 Regulates the Stability of the c-Jun Protein.
AB  - The c-Jun gene encodes a transcription factor that has been implicated in many
      physiological and pathological processes. c-Jun is a highly unstable protein that
      is degraded through a ubiquitination/proteasome-dependent mechanism. However, the
      deubiquitinating enzyme (DUB) that regulates the stability of the c-Jun protein
      requires further investigation. Here, by screening a DUB expression library, we
      identified ubiquitin-specific protease 6 (USP6) and showed that it regulates the
      stability of the c-Jun protein in a manner depending on its enzyme activity. USP6
      interacts with c-Jun and antagonizes its ubiquitination. USP6 overexpression
      upregulates the activity of the downstream signaling pathway mediated by c-Jun/AP
      1 and promotes cell invasion. Moreover, many aberrant genes that are upregulated
      in USP6 translocated nodular fasciitis are great potential targets regulated by c
      Jun. Based on our data, USP6 is an enzyme that deubiquitinates c-Jun and
      regulates its downstream cellular functions.

PMID- 29061732
TI  - Sld5 Ensures Centrosomal Resistance to Congression Forces by Preserving
      Centriolar Satellites.
AB  - The migration of chromosomes during mitosis is mediated primarily by kinesins
      that bind to the chromosomes and move along the microtubules, exerting pulling
      and pushing forces on the centrosomes. We report that a DNA replication protein,
      Sld5, localizes to the centrosomes, resisting the microtubular pulling forces
      experienced during chromosome congression. In the absence of Sld5, centriolar
      satellites, which normally cluster around the centrosomes, are dissipated
      throughout the cytoplasm, resulting in the loss of their known function of
      recruiting the centrosomal protein, pericentrin. We observed that Sld5-deficient
      centrosomes lacking pericentrin were unable to endure the CENP-E- and Kid
      mediated microtubular forces that converge on the centrosomes during chromosome
      congression, resulting in monocentriolar and acentriolar spindle poles. The minus
      end-directed kinesin-14 motor protein, HSET, sustains the traction forces that
      mediate centrosomal fragmentation in Sld5-depleted cells. Thus, we report that a
      DNA replication protein has an as yet unknown function of ensuring spindle pole
      resistance to traction forces exerted during chromosome congression.

PMID- 29061733
TI  - Creation of Stable Heterothallic Strains of Komagataella phaffii Enables
      Dissection of Mating Gene Regulation.
AB  - The methylotrophic yeast Komagataella phaffii (Pichia pastoris) is homothallic
      and has been reported to switch mating type by an ancient inversion mechanism.
      Two mating-type (MAT) loci include homologs of the MATa and MATalpha
      transcription factor genes, with the expression from one locus downregulated by
      telomere position effects. However, not much is known about mating gene
      regulation, since the mixture of mating types complicates detailed
      investigations. In this study, we developed K. phaffii strains with stable mating
      types by deletion of the inverted-repeat region required for mating-type
      switching. These heterothallic strains retain their ability to mate with cells of
      the opposite mating type and were used to further elucidate mating gene
      regulation. Functional analysis of MAT mutant strains revealed the essential role
      of MATa2 and MATalpha1 in diploid cell formation. Disruption of MATa1 or
      MATalpha2 did not affect mating; however, in diploid cells, both genes are
      required for sporulation and the repression of shmoo formation. The heterothallic
      strains generated in this study allowed the first detailed characterization of
      mating gene regulation in K. phaffii They will be a valuable tool for further
      studies investigating cell-type-specific behavior and will enable in-depth
      genetic analyses and strain hybridization in this industrially relevant yeast
      species.

PMID- 29061735
TI  - Backlash prompts WHO to withdraw "goodwill ambassador" role from Mugabe.

PMID- 29061734
TI  - A computational study on the influence of insect wing geometry on bee flight
      mechanics.
AB  - Two-dimensional computational fluid dynamics (CFD) is applied to better
      understand the effects of wing cross-sectional morphology on flow field and force
      production. This study investigates the influence of wing cross-section on insect
      scale flapping flight performance, for the first time, using a morphologically
      representative model of a bee (Bombus pensylvanicus) wing. The bee wing cross
      section was determined using a micro-computed tomography scanner. The results of
      the bee wing are compared with flat and elliptical cross-sections, representative
      of those used in modern literature, to determine the impact of profile variation
      on aerodynamic performance. The flow field surrounding each cross-section and the
      resulting forces are resolved using CFD for a flight speed range of 1 to 5 m/s. A
      significant variation in vortex formation is found when comparing the ellipse and
      flat plate with the true bee wing. During the upstroke, the bee and approximate
      wing cross-sections have a much shorter wake structure than the flat plate or
      ellipse. During the downstroke, the flat plate and elliptical cross-sections
      generate a single leading edge vortex, while the approximate and bee wings
      generate numerous, smaller structures that are shed throughout the stroke.
      Comparing the instantaneous aerodynamic forces on the wing, the ellipse and flat
      plate sections deviate progressively with velocity from the true bee wing. Based
      on the present findings, a simplified cross-section of an insect wing can
      misrepresent the flow field and force production. We present the first
      aerodynamic study using a true insect wing cross-section and show that the wing
      corrugation increases the leading edge vortex formation frequency for a given set
      of kinematics.

PMID- 29061736
TI  - A Drug Repositioning Approach Reveals that Streptococcus mutans Is Susceptible to
      a Diverse Range of Established Antimicrobials and Nonantibiotics.
AB  - Streptococcus mutans is the primary causative agent of dental caries and
      contributes to the multispecies biofilm known as dental plaque. An adenylate
      kinase-based assay was optimized for S. mutans to detect cell lysis when exposed
      to the Selleck library (Selleck Chemical, Houston, TX) of 853 FDA-approved drugs
      in, to our knowledge, the first high-throughput drug screen in S. mutans We found
      126 drugs with activity against S. mutans planktonic cultures, and they were
      classified into six categories: antibacterials (61), antineoplastics (23), ion
      channel effectors (9), other antimicrobials (7), antifungals (6), and other (20).
      These drugs were also tested for activity against S. mutans biofilm cultures, and
      24 compounds were found to inhibit biofilm formation, 6 killed preexisting
      biofilms, 84 exhibited biofilm inhibition and killing activity, and 12 had no
      activity against biofilms. The activities of 9 selected compounds that exhibited
      antimicrobial activity were further characterized for their activity against S.
      mutans planktonic and biofilm cultures. Together, our results suggest that S.
      mutans exhibits a susceptibility profile to a diverse array of established and
      novel antibacterials.

PMID- 29061729
TI  - Plasma 25-Hydroxyvitamin D Concentration and Risk of Islet Autoimmunity.
AB  - We examined the association between plasma 25-hydroxyvitamin D [25(OH)D]
      concentration and islet autoimmunity (IA) and whether vitamin D gene
      polymorphisms modify the effect of 25(OH)D on IA risk. We followed 8,676 children
      at increased genetic risk of type 1 diabetes at six sites in the U.S. and Europe.
      We defined IA as positivity for at least one autoantibody (GADA, IAA, or IA-2A)
      on two or more visits. We conducted a risk set sampled nested case-control study
      of 376 IA case subjects and up to 3 control subjects per case subject. 25(OH)D
      concentration was measured on all samples prior to, and including, the first IA
      positive visit. Nine polymorphisms in VDR, CYP24A, CYP27B1, GC, and RXRA were
      analyzed as effect modifiers of 25(OH)D. Adjusting for HLA-DR-DQ and ancestry,
      higher childhood 25(OH)D was associated with lower IA risk (odds ratio = 0.93 for
      a 5 nmol/L difference; 95% CI 0.89, 0.97). Moreover, this association was
      modified by VDR rs7975232 (interaction P = 0.0072), where increased childhood
      25(OH)D was associated with a decreasing IA risk based upon number of minor
      alleles: 0 (1.00; 0.93, 1.07), 1 (0.92; 0.89, 0.96), and 2 (0.86; 0.80, 0.92).
      Vitamin D and VDR may have a combined role in IA development in children at
      increased genetic risk for type 1 diabetes.

PMID- 29061737
TI  - Antifungal Activity of Oleylphosphocholine on In Vitro and In Vivo Candida
      albicans Biofilms.
AB  - In this study, we investigated the potential antifungal activity of the
      alkylphospholipid oleylphosphocholine (OlPC), a structural analogue of
      miltefosine, on in vitro and in vivoCandida albicans biofilm formation. The
      effect of OlPC on in vitro and in vivoC. albicans biofilms inside triple-lumen
      polyurethane catheters was studied. In vivo biofilms were developed
      subcutaneously after catheter implantation on the lower back of Sprague-Dawley
      rats. Animals were treated orally with OlPC (20 mg/kg of body weight/day) for 7
      days. The effect of OlPC on biofilms that developed on the mucosal surface was
      studied in an ex vivo model of oral candidiasis. The role of OlPC in C. albicans
      morphogenesis was investigated by using hypha-inducing media, namely, Lee,
      Spider, and RPMI 1640 media. OlPC displayed activity against both planktonic
      cells and in vitroC. albicans biofilms. To completely abolish preformed, 24-h-old
      biofilms, higher concentrations (8, 10, and 13 mg/liter) were needed. Moreover,
      OlPC was able to reduce C. albicans biofilms formed by caspofungin-resistant
      clinical isolates and acted synergistically when combined with caspofungin. The
      daily oral administration of OlPC significantly reduced in vivoC. albicans
      biofilms that developed subcutaneously. In addition, OlPC decreased biofilm
      formation on mucosal surfaces. Interestingly, the application of subinhibitory
      concentrations of OlPC already inhibited the yeast-to-hypha transition, a crucial
      virulence factor of C. albicans We document, for the first time, the effects of
      OlPC on C. albicans cells and suggest the potential use of OlPC for the treatment
      of C. albicans biofilm-associated infections.

PMID- 29061739
TI  - Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and
      Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult
      Volunteers.
AB  - Bedaquiline is a diarylquinoline that specifically inhibits mycobacterial ATP
      synthase. Bedaquiline has been used to effectively treat tuberculosis (TB) caused
      by drug-susceptible and drug-resistant Mycobacterium tuberculosis Rifamycins are
      a cornerstone of combination drug regimens for the treatment of TB. This phase 1,
      open-label, randomized, controlled trial evaluated the effect of steady-state
      dosing of rifabutin or rifampin on the safety, tolerability, and pharmacokinetics
      of bedaquiline given as a single dose. Thirty-three healthy subjects were
      enrolled to receive a 400-mg single oral dose of bedaquiline at two time points,
      on study days 1 and 29. Subjects were randomly assigned to once daily oral doses
      of rifabutin (300 mg/day, n = 17) or rifampin (600 mg/day, n = 16) during period
      2 from days 20 to 41. Serial blood sampling for bedaquiline measurement occurred
      on days 1 and 29 through 336 h after bedaquiline administration. The day 29
      bedaquiline pharmacokinetic parameter estimates were compared to the
      corresponding day 1 estimates for each rifamycin group. Steady-state rifampin
      reduced bedaquiline AUC0-336 approximately 45%, from 47.69 h.MUg/ml in period 1
      to 26.33 h.MUg/ml in period 2. Bedaquiline apparent clearance accelerated 24% in
      rifampin-treated subjects from 6.59 liters/h in period 1 to 8.19 liters/h in
      period 2. Steady-state rifabutin resulted in little quantitative impact on
      bedaquiline exposure but was associated with grade 3 and 4 adverse events before
      and after the day 29 bedaquiline dose. Dosage adjustments may therefore be
      necessary to ensure that bedaquiline plasma concentrations reach therapeutic
      levels safely when combining bedaquiline and rifamycins in TB treatment regimens.
      (This single-site, randomized, open-label, prospective study in healthy adult
      volunteers was registered at Clinicaltrials.gov under registration no.
      NCT01341184.).

PMID- 29061738
TI  - Peptidoglycan Cross-Linking Activity of l,d-Transpeptidases from Clostridium
      difficile and Inactivation of These Enzymes by beta-Lactams.
AB  - In most bacteria, the essential targets of beta-lactam antibiotics are the d,d
      transpeptidases that catalyze the last step of peptidoglycan polymerization by
      forming 4->3 cross-links. The peptidoglycan of Clostridium difficile is unusual
      since it mainly contains 3->3 cross-links generated by l,d-transpeptidases. To
      gain insight into the characteristics of C. difficile peptidoglycan cross-linking
      enzymes, we purified the three putative C. difficile l,d-transpeptidase
      paralogues LdtCd1, LdtCd2, and LdtCd3, which were previously identified by
      sequence analysis. The catalytic activities of the three proteins were assayed
      with a disaccharide-tetrapeptide purified from the C. difficile cell wall. LdtCd2
      and LdtCd3 catalyzed the formation of 3->3 cross-links (l,d-transpeptidase
      activity), the hydrolysis of the C-terminal d-Ala residue of the disaccharide
      tetrapeptide substrate (l,d-carboxypeptidase activity), and the exchange of the C
      terminal d-Ala for d-Met. LdtCd1 displayed only l,d-carboxypeptidase activity.
      Mass spectrometry analyses indicated that LdtCd1 and LdtCd2 were acylated by beta
      lactams belonging to the carbapenem (imipenem, meropenem, and ertapenem),
      cephalosporin (ceftriaxone), and penicillin (ampicillin) classes. Acylation of
      LdtCd3 by these beta-lactams was not detected. The acylation efficacy of LdtCd1
      and LdtCd2 was higher for the carbapenems (480 to 6,600 M-1 s-1) than for
      ampicillin and ceftriaxone (3.9 to 82 M-1 s-1). In contrast, the efficacy of the
      hydrolysis of beta-lactams by LdtCd1 and LdtCd2 was higher for ampicillin and
      ceftriaxone than for imipenem. These observations indicate that LdtCd1 and LdtCd2
      are inactivated only by beta-lactams of the carbapenem class due to a combination
      of rapid acylation and the stability of the resulting covalent adducts.

PMID- 29061740
TI  - Interplay between Antibiotic Efficacy and Drug-Induced Lysis Underlies Enhanced
      Biofilm Formation at Subinhibitory Drug Concentrations.
AB  - Subinhibitory concentrations of antibiotics have been shown to enhance biofilm
      formation in multiple bacterial species. While antibiotic exposure has been
      associated with modulated expression of many biofilm-related genes, the
      mechanisms of drug-induced biofilm formation remain a focus of ongoing research
      efforts and may vary significantly across species. In this work, we investigate
      antibiotic-induced biofilm formation in Enterococcus faecalis, a leading cause of
      nosocomial infections. We show that biofilm formation is enhanced by
      subinhibitory concentrations of cell wall synthesis inhibitors but not by
      inhibitors of protein, DNA, folic acid, or RNA synthesis. Furthermore, enhanced
      biofilm is associated with increased cell lysis, increases in extracellular DNA
      (eDNA) levels, and increases in the density of living cells in the biofilm. In
      addition, we observe similar enhancement of biofilm formation when cells are
      treated with nonantibiotic surfactants that induce cell lysis. These findings
      suggest that antibiotic-induced biofilm formation is governed by a trade-off
      between drug toxicity and the beneficial effects of cell lysis. To understand
      this trade-off, we developed a simple mathematical model that predicts changes in
      antibiotic-induced biofilm formation due to external perturbations, and we
      verified these predictions experimentally. Specifically, we demonstrate that
      perturbations that reduce eDNA (DNase treatment) or decrease the number of living
      cells in the planktonic phase (a second antibiotic) decrease biofilm induction,
      while chemical inhibitors of cell lysis increase relative biofilm induction and
      shift the peak to higher antibiotic concentrations. Overall, our results offer
      experimental evidence linking cell wall synthesis inhibitors, cell lysis,
      increased eDNA levels, and biofilm formation in E. faecalis while also providing
      a predictive quantitative model that sheds light on the interplay between cell
      lysis and antibiotic efficacy in developing biofilms.

PMID- 29061741
TI  - In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore
      Cephalosporin, against Gram-Negative Bacteria.
AB  - Cefiderocol (CFDC; S-649266), a novel parenteral siderophore cephalosporin
      conjugated with a catechol moiety, has a characteristic antibacterial spectrum
      with a potent activity against a broad range of aerobic Gram-negative bacterial
      species, including carbapenem-resistant strains of Enterobacteriaceae and
      nonfermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii
      Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of
      Enterobacteriaceae and nonfermenting bacteria similar to that of ceftazidime. A
      deficiency of the iron transporter PiuA in P. aeruginosa or both CirA and Fiu in
      Escherichia coli caused 16-fold increases in cefiderocol MICs, suggesting that
      these iron transporters contribute to the permeation of cefiderocol across the
      outer membrane. The deficiency of OmpK35/36 in Klebsiella pneumoniae and the
      overproduction of efflux pump MexA-MexB-OprM in P. aeruginosa showed no
      significant impact on the activity of cefiderocol.

PMID- 29061742
TI  - Pharmacokinetics of a Long-Acting Nanoformulated Dolutegravir Prodrug in Rhesus
      Macaques.
AB  - A nanoformulated myristoylated dolutegravir prodrug (NMDTG) was prepared using
      good laboratory practice protocols. Intramuscular injection of NMDTG (118 +/- 8
      mg/ml, 25.5 mg of DTG equivalents/kg of body weight) to three rhesus macaques led
      to plasma DTG levels of 86 +/- 12 and 28 +/- 1 ng/ml on days 35 and 91,
      respectively. The NMDTG platform showed no significant adverse events. Further
      modification may further extend the drug's apparent half-life for human use.

PMID- 29061743
TI  - Vitamin D Compounds Are Bactericidal against Streptococcus mutans and Target the
      Bacitracin-Associated Efflux System.
AB  - Vitamin D analogs were identified as compounds that induced lysis of planktonic
      cultures of Streptococcus mutans in a high-throughput screen of FDA-approved
      drugs. Previous studies have demonstrated that certain derivatives of vitamin D
      possess lytic activity against other bacteria, though the mechanism has not yet
      been established. Through the use of a combinatorial approach, the vitamin D
      derivative doxercalciferol was shown to act synergistically with bacitracin, a
      polypeptide-type drug that is known to interfere with cell wall synthesis,
      suggesting that doxercalciferol may act in a bacitracin-related pathway. Innate
      resistance to bacitracin is attributed to efflux by a conserved ABC-type
      transporter, which in S. mutans is encoded by the mbrABCD operon. S. mutans
      possesses two characterized mechanisms of resistance to bacitracin, the ABC
      transporter, S. mutans bacitracin resistance (Mbr) cassette, consisting of
      MbrABCD, and the rhamnose-glucose polysaccharide (Rgp) system, RgpABCDEFGHI. Loss
      of function of the transporter in DeltambrA and DeltambrD mutants exacerbated the
      effect of the combination of doxercalciferol and bacitracin. Despite conservation
      of a transporter homologous to mbrABCD, the combination of doxercalciferol and
      bacitracin appeared to be synergistic only in streptococcal species. We conclude
      that vitamin D derivatives possess lytic activity against S. mutans and act
      through a mechanism dependent on the bacitracin resistance mechanism of MbrABCD.

PMID- 29061745
TI  - Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment
      of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma
      Membrane Ca2+ Channel.
AB  - Leishmania donovani is the causing agent of visceral leishmaniasis, a common
      infection that affects millions of people from the most underdeveloped countries.
      Miltefosine is the only oral drug to treat infections caused by L. donovani
      Nevertheless, its mechanism of action is not well understood. While miltefosine
      inhibits the synthesis of phosphatidylcholine and also affects the parasite
      mitochondrion, inhibiting the cytochrome c oxidase, it is to be expected that
      this potent drug also produces its effect through other targets. In this context,
      it has been reported that the disruption of the intracellular Ca2+ homeostasis
      represents an important object for the action of drugs in trypanosomatids.
      Recently, we have described a plasma membrane Ca2+ channel in Leishmania
      mexicana, which is similar to the L-type voltage-gated Ca2+ channel (VGCC)
      present in humans. Remarkably, the parasite Ca2+ channel is activated by
      sphingosine, while the L-type VGCC is not affected by this sphingolipid. In the
      present work we demonstrated that, similarly to sphingosine, miltefosine is able
      to activate the plasma membrane Ca2+ channel from L. donovani Interestingly,
      nifedipine, the classical antagonist of the human channel, was not able to fully
      block the parasite plasma membrane Ca2+ channel, indicating that the mechanism of
      interaction is not identical to that of sphingosine. In this work we also show
      that miltefosine is able to strongly affect the acidocalcisomes from L. donovani,
      inducing the rapid alkalinization of these important organelles. In conclusion,
      we demonstrate two new mechanisms of action of miltefosine in L. donovani, both
      related to disruption of parasite Ca2+ homeostasis.

PMID- 29061744
TI  - Molecular Mechanisms of Intrinsic Streptomycin Resistance in Mycobacterium
      abscessus.
AB  - Streptomycin, the first drug used for the treatment of tuberculosis, shows
      limited activity against the highly resistant pathogen Mycobacterium abscessus We
      recently identified two aminoglycoside-acetylating genes [aac(2') and eis2]
      which, however, do not affect susceptibility to streptomycin. This suggests the
      existence of a discrete mechanism of streptomycin resistance. M. abscessus BLASTP
      analysis identified MAB_2385 as a close homologue of the 3"-O-phosphotransferase
      [APH(3")] from the opportunistic pathogen Mycobacterium fortuitum as a putative
      streptomycin resistance determinant. Heterologous expression of MAB_2385 in
      Mycobacterium smegmatis increased the streptomycin MIC, while the gene deletion
      mutant M. abscessus DeltaMAB_2385 showed increased streptomycin susceptibility.
      The MICs of other aminoglycosides were not altered in M. abscessus DeltaMAB_2385.
      This demonstrates that MAB_2385 encodes a specific and prime innate streptomycin
      resistance determinant in M. abscessus We further explored the feasibility of
      applying rpsL-based streptomycin counterselection to generate gene deletion
      mutants in M. abscessus Spontaneous streptomycin-resistant mutants of M.
      abscessus DeltaMAB_2385 were selected, and we demonstrated that the wild-type
      rpsL is dominant over the mutated rpsLK43R in merodiploid strains. In a proof of
      concept study, we exploited this phenotype for construction of a targeted
      deletion mutant, thereby establishing an rpsL-based counterselection method in M.
      abscessus.

PMID- 29061746
TI  - Efficacy and Tolerability Outcomes of a Phase II, Randomized, Open-Label,
      Multicenter Study of a New Water-Dispersible Pediatric Formulation of
      Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium
      falciparum Malaria in African Infants.
AB  - Artemisinin combination therapies are considered the mainstay of malaria
      treatment, but pediatric-friendly formulations for the treatment of infants are
      scarce. We sought to evaluate the efficacy and safety of a new dispersible-tablet
      formulation of dihydroartemisinin/piperaquine phosphate (DHA/PQP) in comparison
      to the marketed tablet (Eurartesim) in the treatment of infants with
      uncomplicated Plasmodium falciparum malaria. Reported here are the results of a
      large phase II, randomized, open-label, multicenter trial conducted in African
      infants (6 to 12 months of age) from Mozambique, Burkina Faso, The Gambia, the
      Democratic Republic of the Congo, and Tanzania. Primary efficacy endpoint was the
      PCR-corrected adequate clinical and parasitological response (ACPR) at day 28.
      Analysis was performed for the intention-to-treat (ITT) and per-protocol (PP)
      populations. A total of 201 patients received the dispersible-tablet formulation,
      and 99 received the conventional one administered as crushed tablets. At day 28,
      the PCR-corrected ACPRs were 86.9% (ITT) and 98.3% (PP) in the dispersible-tablet
      group and 84.9% (ITT) and 100% (PP) in the crushed-tablet group. At day 42, these
      values were 85.9% (ITT) and 96.5% (PP) in the dispersible-tablet group and 82.8%
      (ITT) and 96.4% (PP) in the crushed-tablet group. The comparison between survival
      curves for time to new infections showed no statistically significant differences
      (P = 0.409). The safety and tolerability profile for the two groups was similar
      in terms of type and frequency of adverse events and was consistent with that
      expected in African infants with malaria. A standard 3-day treatment with the new
      dispersible DHA/PQP formulation is as efficacious as the currently used tablet in
      African infants and has a comparable safety profile. (This trial was registered
      at ClinicalTrials.gov under registration no. NCT01992900.).

PMID- 29061747
TI  - Effect of Incubation Temperature on Antibiotic Resistance and Virulence Factors
      of Acinetobacter baumannii ATCC 17978.
AB  - Acinetobacter baumannii is a notorious opportunistic pathogen that is prevalent
      mainly in hospital settings. The ability of A. baumannii to adapt and to survive
      in a range of environments has been a key factor for its persistence and success
      as an opportunistic pathogen. In this study, we investigated the effect of
      temperature on the clinically relevant phenotypes displayed by A. baumannii at 37
      degrees C and 28 degrees C. Surface-associated motility was significantly reduced
      at 28 degrees C, while biofilm formation on plastic surfaces was increased at 28
      degrees C. Decreased susceptibility to aztreonam and increased susceptibility to
      trimethoprim-sulfamethoxazole were observed at 28 degrees C. No differences in
      virulence, as assayed in a Galleria mellonella model, were observed. Proteomic
      analysis showed differential expression of 629 proteins, of which 366 were
      upregulated and 263 were downregulated at 28 degrees C. Upregulation of the Csu
      and iron uptake proteins at 28 degrees C was a key finding for understanding some
      of the phenotypes displayed by A. baumannii at 28 degrees C.

PMID- 29061749
TI  - Heteroresistance to Piperacillin-Tazobactam in Clinical Isolates of Escherichia
      coli Sequence Type 131.

PMID- 29061748
TI  - In Vitro Evaluation of Povidone-Iodine and Chlorhexidine against Outbreak and
      Nonoutbreak Strains of Mycobacterium abscessus Using Standard Quantitative
      Suspension and Carrier Testing.
AB  - Povidone-iodine (PI) and chlorhexidine (CHX) are widely used antiseptics active
      against conventional Staphylococcus aureus, Enterobacteriaceae, Candida species,
      and viruses, but their efficacy against Mycobacterium abscessus remains unproven.
      We determined the in vitro potency of alcoholic PI and CHX against M. abscessus
      subsp. abscessus (ATCC 19977), M. abscessus subsp. bolletii (BCRC 16915), and our
      outbreak strain of M. abscessus subsp. massiliense (TPE 101) in reference to
      Staphylococcus aureus (ATCC 29213) by standard quantitative suspension and
      carrier methods (EN 14563). By suspension, all mycobacterial strains compared to
      S. aureus were significantly more resistant to CHX, but not PI. By carrier, the
      mean logarithmic reductions (LR) achieved by PI under clean (dirty) conditions
      were 6.575 (2.482), 5.540 (2.298), 4.595 (1.967), and 1.173 (0.889), while those
      achieved by CHX under clean (dirty) conditions were 3.164 (5.445), 5.307 (2.564),
      3.844 (2.232), and 0.863 (0.389) for S. aureus, M. abscessus subsp. bolletii, M.
      abscessus subsp. abscessus, and M. abscessus subsp. massiliense, respectively. M.
      abscessus subsp. massiliense (outbreak strain) was significantly more resistant
      than the other tested strains to PI and CHX. By both methods, the mean LR
      achieved by PI was higher than for CHX for all mycobacterial strains, but under
      dirty conditions, neither antiseptic was effectively mycobactericidal (LR < 5).
      These preliminary findings caution against the universal replacement of PI with
      CHX as the first-line skin antiseptic, since all M. abscessus isolates were
      resistant to CHX. More studies are needed to establish the best practice for skin
      antisepsis if mycobacterial infections are also to be prevented.

PMID- 29061751
TI  - Intrapulmonary Pharmacokinetics of Laninamivir, a Neuraminidase Inhibitor, after
      a Single Nebulized Administration of Laninamivir Octanoate in Healthy Japanese
      Subjects.
AB  - A single dose of laninamivir octanoate (LO) inhaled using a dry powder inhaler
      (DPI) is effective for the treatment and prophylaxis of influenza. Nebulizers are
      an option for pediatric and elderly patients who may have difficulty in using a
      DPI. A single-center, open-label study was conducted to evaluate the plasma and
      intrapulmonary pharmacokinetics (PK) of laninamivir after a single nebulized
      administration of LO in healthy male Japanese subjects for identifying a safe and
      effective dosage regimen for a nebulizer. A single dose of LO (40 to 320 mg) was
      administered using a nebulizer, and plasma concentrations of LO and laninamivir
      were analyzed up to 168 h after inhalation by validated liquid chromatography
      tandem mass spectrometry methods. Subgroups of 6 subjects each underwent
      bronchoalveolar lavage at specified time intervals over 4 to 168 h following a
      single nebulized administration of LO (160 mg), and the concentrations in
      epithelial lining fluid (ELF) were calculated by the urea diffusion method. PK
      parameters were determined by noncompartment analysis. Inhaled nebulized LO was
      found to be safe and well tolerated up to the highest dose evaluated (320 mg).
      Plasma laninamivir concentrations increased almost dose proportionally.
      Laninamivir concentrations in ELF exceeded the 50% inhibitory concentrations for
      viral neuraminidase up to 168 h after the nebulized inhalation of 160 mg LO.
      Thus, similarly to the DPI, ELF concentration profiles of laninamivir after a
      single nebulized administration support its long-lasting effect against influenza
      virus infection. This study has been registered at JAPIC Clinical Trials
      Information (http://www.clinicaltrials.jp/) under registration no. JAPIC CTI
      152996.

PMID- 29061750
TI  - Dissemination and Characteristics of a Novel Plasmid-Encoded Carbapenem
      Hydrolyzing Class D beta-Lactamase, OXA-436, Found in Isolates from Four Patients
      at Six Different Hospitals in Denmark.
AB  - The diversity of OXA-48-like carbapenemases is continually expanding. In this
      study, we describe the dissemination and characteristics of a novel carbapenem
      hydrolyzing class D beta-lactamase (CHDL) named OXA-436. In total, six OXA-436
      producing Enterobacteriaceae isolates, including Enterobacter asburiae (n = 3),
      Citrobacter freundii (n = 2), and Klebsiella pneumoniae (n = 1), were identified
      in four patients in the period between September 2013 and April 2015. All three
      species of OXA-436-producing Enterobacteriaceae were found in one patient. The
      amino acid sequence of OXA-436 showed 90.4 to 92.8% identity to the amino acid
      sequences of other acquired OXA-48-like variants. Expression of OXA-436 in
      Escherichia coli and kinetic analysis of purified OXA-436 revealed an activity
      profile similar to that of OXA-48 and OXA-181, with activity against penicillins,
      including temocillin; limited or no activity against extended-spectrum
      cephalosporins; and activity against carbapenems. The blaOXA-436 gene was located
      on a conjugative ~314-kb IncHI2/IncHI2A plasmid belonging to plasmid multilocus
      sequence typing sequence type 1 in a region surrounded by chromosomal genes
      previously identified to be adjacent to blaOXA genes in Shewanella spp. In
      conclusion, OXA-436 is a novel CHDL with functional properties similar to those
      of OXA-48-like CHDLs. The described geographical spread among different
      Enterobacteriaceae and the plasmid location of blaOXA-436 illustrate its
      potential for further dissemination.

PMID- 29061753
TI  - Assessing the Combined Antibacterial Effect of Isoniazid and Rifampin on Four
      Mycobacterium tuberculosis Strains Using In Vitro Experiments and Response
      Surface Modeling.
AB  - While isoniazid and rifampin have been the cornerstone of tuberculosis therapy
      caused by drug-susceptible Mycobacterium tuberculosis for more than 40 years,
      their combined action has never been thoroughly assessed by modern quantitative
      pharmacology approaches. The aims of this work were to perform in vitro
      experiments and mathematical modeling of the antibacterial effect of isoniazid
      and rifampin alone and in combination against various strains of Mycobacterium
      tuberculosis After MIC determination of H37Rv and three strains belonging to the
      Beijing, Euro-American, and Indo-Oceanic lineages, the antibacterial effects of
      isoniazid and rifampin alone and in combination were studied in static time-kill
      experiments. A sigmoidal maximum effect model (Hill equation) and a response
      surface model were used to describe the effect of the drugs alone and in
      combination, respectively. The killing effect of isoniazid and rifampin alone
      were well described by the Hill equation. Rifampin displayed a more concentration
      dependent effect than isoniazid around the MIC. The pharmacodynamics parameters
      of each drug (maximal effect, median effect concentration, and coefficient of
      sigmoidicity) were quite similar between the four strains. The response-surface
      model from Minto et al. fit data of combined effect very well with low bias and
      imprecision (C. F. Minto, T. W. Schnider, T. G. Short, K. M. Gregg, A. Gentilini,
      Anesthesiology 92:1603-1616, 2000, https://doi.org/10.1097/00000542-200006000
      00017). Response-surface modeling showed that the combined action of isoniazid
      and rifampin was synergistic for the H37Rv, Beijing, and Euro-American strains
      but only additive for the Indo-Oceanic strain. This study can serve as a
      motivating example for preclinical evaluation of combined action of
      antituberculous drugs.

PMID- 29061752
TI  - Methionine Ameliorates Polymyxin-Induced Nephrotoxicity by Attenuating Cellular
      Oxidative Stress.
AB  - Polymyxins are a last line of defense against multidrug-resistant Gram-negative
      pathogens. Recent pharmacological data show that intravenous polymyxins can cause
      nephrotoxicity in up to 60% of patients, and the plasma concentrations of
      polymyxins achieved with the currently recommended dosage regimens are suboptimal
      in a large proportion of patients. Simply increasing the daily dose of polymyxins
      is not possible due to nephrotoxicity. This study aimed to examine the protective
      effect of methionine against polymyxin-induced nephrotoxicity. Methionine (400
      mg/kg of body weight), polymyxin B (35 mg/kg), a combination of methionine (100
      or 400 mg/kg) and polymyxin B, and saline were administered to mice twice daily
      over 3.5 days. Kidneys were collected immediately at the end of the experiment
      for histological examination. The effect of methionine on the pharmacokinetics of
      polymyxin B was investigated in rats. The attenuation of polymyxin B (0.75 mM)
      induced mitochondrial superoxide production by methionine (10.0 mM) was examined
      in rat kidney (NRK-52E) cells. Histological results revealed that the polymyxin
      induced nephrotoxicity in mice was ameliorated by methionine in a dose-dependent
      manner. The methionine doses were well tolerated in the mice and rats, and the
      pharmacokinetics of polymyxin B in rats were not affected by methionine. In the
      group receiving polymyxin B-methionine, the total body clearance of polymyxin B
      was very similar to that in the group receiving polymyxin B alone (3.71 +/- 0.57
      versus 3.12 +/- 1.66 ml/min/kg, P > 0.05). A substantial attenuation of polymyxin
      induced mitochondrial superoxide production in NRK-52E cells was observed
      following pretreatment with methionine. Our results demonstrate that
      coadministration of methionine significantly ameliorated polymyxin-induced
      nephrotoxicity and decreased mitochondrial superoxide production in renal tubular
      cells.

PMID- 29061755
TI  - Oral Tobramycin Prophylaxis Prior to Colorectal Surgery Is Not Associated with
      Systemic Uptake.
AB  - Preoperative oral prophylaxis with nonabsorbable antibiotics has been reported to
      reduce the risk of surgical site infections after colorectal surgery. This
      prospective study was conducted to evaluate the risk of toxic side effects by
      measuring postoperative serum tobramycin levels in patients who received a 3-day
      prophylaxis with tobramycin and colistin prior to colorectal surgery. In all
      patients, serum tobramycin concentrations were below the detection limit (0.3
      mg/liter), implying a low risk of toxicity.

PMID- 29061754
TI  - Antimicrobial Activities of Aztreonam-Avibactam and Comparator Agents against
      Contemporary (2016) Clinical Enterobacteriaceae Isolates.
AB  - A total of 10,451 contemporary (2016) Enterobacteriaceae isolates from 84 U.S.
      medical centers and 116 metallo-beta-lactamase- and/or OXA-48-like-producing
      Enterobacteriaceae isolates from other countries were tested against aztreonam
      avibactam and comparators. All U.S. isolates were inhibited at aztreonam
      avibactam MICs of <=8 MUg/ml (MIC50, <=0.03 MUg/ml; MIC90, 0.12 MUg/ml),
      including Klebsiella pneumoniae carbapenemase-producing isolates (n = 102; MIC50,
      0.25 MUg/ml; MIC90, 0.5 MUg/ml), multidrug-resistant isolates (n = 876; MIC50,
      0.06 MUg/ml; MIC90, 0.25 MUg/ml), and extensively drug-resistant isolates (n =
      111; MIC50, 0.12 MUg/ml; MIC90, 0.5 MUg/ml). The highest aztreonam-avibactam MIC
      value among ex-U.S. isolates was 4 MUg/ml.

PMID- 29061757
TI  - Assessing Noninferiority in Treatment Trials for Severe Infectious Diseases: an
      Extension to the Entire Follow-Up Period Using a Cure-Death Multistate Model.
AB  - In current and former clinical trials for the development of antibacterial drugs,
      various primary endpoints have been used, and treatment effects are evaluated
      mostly in noninferiority analyses at the end of follow-up, which varies between
      studies. A more convincing and highly patient-relevant statement would be a
      noninferiority assessment over the entire follow-up period with cure and death as
      coprimary endpoints, while preserving the desired alpha level for statistical
      testing. To account for the time-dynamic pattern of cure and death, we apply a
      cure-death multistate model. The endpoint of interest is "get cured and stay
      alive over time." Noninferiority between treatments over the entire follow-up
      period is studied by means of one-sided confidence bands provided by a flexible
      resampling technique. We illustrate the technique by applying it to a recently
      published study and establish noninferiority in being cured and alive over a time
      frame of interest for the entire population, patients with hospital-acquired
      pneumonia, but not for the subset of patients with ventilator-associated
      pneumonia. Our analysis improves the original results in the sense that our
      endpoint is more patient benefiting, a stronger noninferiority statement is
      demonstrated, and the time dependency of cure and death, competing events, and
      different follow-up times is captured. Multistate methodology combined with
      confidence bands adds a valuable statistical tool for clinical trials in the
      context of infection control. The framework is not restricted to the cure-death
      model but can be adapted to more complex multistate endpoints and equivalence or
      superiority analyses.

PMID- 29061756
TI  - Functional Involvement of Leishmania donovani Tryparedoxin Peroxidases during
      Infection and Drug Treatment.
AB  - The parasite Leishmania donovani causes visceral leishmaniasis, a potentially
      fatal disease. The parasites survive within mammalian macrophages and express a
      unique set of enzymes, the tryparedoxin peroxidases, for their defense against
      oxidative stress generated by the host. In this study, we demonstrate different
      roles of two distinct enzymes, the mitochondrial tryparedoxin peroxidase (mTXNPx)
      and the cytosolic tryparedoxin peroxidase (cTXNPx), in defending the parasites
      against mitochondrial and exogenous oxidative stress during infection and drug
      treatment. Our findings indicate a greater increase in cTXNPx expression in
      response to exogenous oxidative stress and a higher elevation of mTXNPx
      expression in response to mitochondrial or endogenous stress created by
      respiratory chain complex inhibitors. Overexpression of cTXNPx in Leishmania
      showed improved protection against exogenous stress and enhanced protection
      against mitochondrial stress in parasites overexpressing mTXNPx. Further,
      parasites overexpressing cTXNPx infected host cells with increased efficiency at
      early times of infection compared to control parasites or parasites
      overexpressing mTXNPx. The mTXNPx-overexpressing parasites maintained higher
      infection at later times. Higher mTXNPx expression occurred in wild-type
      parasites on exposure to miltefosine, while treatment with antimony elevated
      cTXNPx expression. Parasites resistant to miltefosine or antimony demonstrated
      increased expression of mTXNPx, as well as cTXNPx. In summary, this study
      provides evidence of distinct roles of the two enzymes defined by virtue of their
      localization during infection and drug treatment.

PMID- 29061758
TI  - Praziquantel Targets M1 Macrophages and Ameliorates Splenomegaly in Chronic
      Schistosomiasis.
AB  - Splenomegaly is a common feature of many infectious diseases, including
      schistosomiasis japonica. However, the immunopathogenesis and the treatment of
      splenomegaly due to schistosomiasis have been largely neglected. Praziquantel
      (PZQ), a classical schistosomicide, has been demonstrated by us and others to
      have antifibrotic and anti-inflammatory activities against schistosomiasis. In
      this study, we investigated the effect of PZQ on alleviating the splenomegaly
      caused by Schistosoma japonicum infection in mice. The results showed that the
      number of macrophages, especially the number of M1 macrophages, was significantly
      increased in the enlarged spleens of infected mice (P < 0.001). After PZQ
      treatment for 4 weeks, the number of splenic macrophages, especially the number
      of M1 macrophages, was significantly reduced (P < 0.001) by the way of apoptosis,
      and another schistosomicide, mefloquine, had no effect either on the splenomegaly
      or on reducing the number of macrophages. Furthermore, by using the murine
      macrophage line RAW 264.7, we found that PZQ could inhibit the formation of the
      NLRP3 inflammasome and attenuate phagocytic activity in M1 macrophages. Thus, our
      studies suggest that PZQ plays a powerful role in ameliorating the splenomegaly
      caused by S. japonicum infection, which presents a new strategy for the therapy
      of splenomegaly resulting from other pathological conditions.

PMID- 29061759
TI  - In Vitro Activity and MIC of Sitafloxacin against Multidrug-Resistant and
      Extensively Drug-Resistant Mycobacterium tuberculosis Isolated in Thailand.
AB  - New fluoroquinolones (FQs) have been shown to be more active against drug
      resistant Mycobacterium tuberculosis strains than early FQs, such as ofloxacin.
      Sitafloxacin (STFX) is a new fluoroquinolone with in vitro activity against a
      broad range of bacteria, including M. tuberculosis This study aimed to determine
      the in vitro activity of STFX against all groups of drug-resistant strains,
      including multidrug-resistant M. tuberculosis (MDR M. tuberculosis), MDR M.
      tuberculosis with quinolone resistance (pre-XDR), and extensively drug-resistant
      (XDR) strains. A total of 374 drug-resistant M. tuberculosis strains were tested
      for drug susceptibility by the conventional proportion method, and 95 strains
      were randomly submitted for MIC determination using the microplate alamarBlue
      assay (MABA). The results revealed that all the drug-resistant strains were
      susceptible to STFX at a critical concentration of 2 MUg/ml. Determination of the
      MIC90s of the strains showed different MIC levels; MDR M. tuberculosis strains
      had a MIC90 of 0.0625 MUg/ml, whereas pre-XDR and XDR M. tuberculosis strains had
      identical MIC90s of 0.5 MUg/ml. Common mutations within the quinolone resistance
      determining region (QRDR) of gyrA and/or gyrB did not confer resistance to STFX,
      except that double mutations of GyrA at Ala90Val and Asp94Ala were found in
      strains with a MIC of 1.0 MUg/ml. The results indicated that STFX had potent in
      vitro activity against all the groups of drug-resistant M. tuberculosis strains
      and should be considered a new repurposed drug for treatment of multidrug
      resistant and extensively drug-resistant TB.

PMID- 29061760
TI  - Combinations of Respiratory Chain Inhibitors Have Enhanced Bactericidal Activity
      against Mycobacterium tuberculosis.
AB  - As an obligate aerobe, Mycobacterium tuberculosis uses its electron transport
      chain (ETC) to produce energy via oxidative phosphorylation. This pathway has
      recently garnered a lot of attention and is a target for several new
      antimycobacterials. We tested the respiratory adaptation of M. tuberculosis to
      phenoxyalkylbenzimidazoles (PABs), compounds proposed to target QcrB, a component
      of the cytochrome bc1 complex. We show that M. tuberculosis is able to reroute
      its ETC to provide temporary resistance to PABs. However, combination treatment
      of PAB with agents targeting other components of the electron transport chain
      overcomes this respiratory flexibility. PAB in combination with clofazimine
      resulted in synergistic killing of M. tuberculosis under both replicating and
      nonreplicating conditions. PABs in combination with bedaquiline demonstrated
      antagonism at early time points, particularly under nonreplicating conditions.
      However, this antagonistic effect disappeared within 3 weeks, when PAB-BDQ
      combinations became highly bactericidal; in some cases, they were better than
      either drug alone. This study highlights the potential for combination treatment
      targeting the ETC and supports the development of PABs as part of a novel drug
      regimen against M. tuberculosis.

PMID- 29061762
TI  - Descriptive analysis of the medical care performed in the Spanish military Role 1
      Medical Treatment Facility deployed in Operation 'Inherent Resolve' (Iraq), 2015
      2016.
AB  - INTRODUCTION: Operation 'Inherent Resolve' was approved by the United Nations in
      August 2014 with the objective of suppressing the Islamic State in Iraq and the
      Levant and increasing the region's stability. The mission of the Spanish military
      forces within this was to direct training missions for the Iraqi Army. The aim of
      this study is to analyse the medical care provided in the Spanish Role 1 deployed
      medical treatment facility during Operation 'Apoyo a Irak'. METHODS: A cross
      sectional, descriptive and retrospective study was conducted between 15 December
      2015 and 18 November 2016. The study population comprised all personnel treated
      at the Spanish Role 1 medical treatment facility of the 'Gran Capitan' base in
      Besmaya, Iraq. RESULTS: During the study period, a total of 2208 consultations
      were performed, 1547 of which were first consultations. The predominant type of
      medical care was categorised as 'traumatology' (n=438; 19.8%), followed by
      'healing of wounds and minor surgical processes' (n=332; 15%), 'acute upper
      respiratory tract infections' (n=267; 12%), 'dermatology' (n=214; 9.6%) and
      'gastroenterology' (n=214; 9.6%). Twenty-eight patients (1.2%) required care in
      the upper medical echelon of care, three of whom were urgently evacuated. Oral
      diseases were the main reason for evacuation to the next medical echelon. Four
      patients were repatriated to the national territory for medical reasons. One
      death was recorded due to a vehicle accident. CONCLUSIONS: The results of our
      study reinforce those found in similar recent international missions in which the
      Spanish Armed Forces and other allied armies have deployed a Role 1 medical
      treatment facility. Military physicians deploying on operations such as Iraq
      should have up-to-date training in emergency and primary care medicine, with
      special emphasis on basic trauma knowledge and performing minor surgical
      processes.

PMID- 29061761
TI  - Antileishmanial Efficacy and Pharmacokinetics of DB766-Azole Combinations.
AB  - Given the limitations of current antileishmanial drugs and the utility of oral
      combination therapy for other infections, developing an oral combination against
      visceral leishmaniasis should be a high priority. In vitro combination studies
      with DB766 and antifungal azoles against intracellular Leishmania donovani showed
      that posaconazole and ketoconazole, but not fluconazole, enhanced DB766 potency.
      Pharmacokinetic analysis of DB766-azole combinations in uninfected Swiss Webster
      mice revealed that DB766 exposure was increased by higher posaconazole and
      ketoconazole doses, while DB766 decreased ketoconazole exposure. In L. donovani
      infected BALB/c mice, DB766-posaconazole combinations given orally for 5 days
      were more effective than DB766 or posaconazole alone. For example, 81% +/- 1%
      (means +/- standard errors) inhibition of liver parasite burden was observed for
      37.5 mg/kg of body weight DB766 plus 15 mg/kg posaconazole, while 37.5 mg/kg
      DB766 and 15 mg/kg posaconazole administered as monotherapy gave 40% +/- 5% and
      21% +/- 3% inhibition, respectively. Combination index (CI) analysis indicated
      that synergy or moderate synergy was observed in six of nine combined dose
      groups, while the other three were nearly additive. Liver concentrations of DB766
      and posaconazole increased in almost all combination groups compared to
      monotherapy groups, although many increases were not statistically significant.
      For DB766-ketoconazole combinations evaluated in this model, two were
      antagonistic, one displayed synergy, and one was nearly additive. These data
      indicate that the efficacy of DB766-posaconazole and DB766-ketoconazole
      combinations in vivo is influenced in part by the pharmacokinetics of the
      combination, and that the former combination deserves further consideration in
      developing new treatment strategies against visceral leishmaniasis.

PMID- 29061764
TI  - The Structural Basis for Complement Inhibition by Gigastasin, a Protease
      Inhibitor from the Giant Amazon Leech.
AB  - Complement is crucial to the immune response, but dysregulation of the system
      causes inflammatory disease. Complement is activated by three pathways:
      classical, lectin, and alternative. The classical and lectin pathways are
      initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases. Given
      the role of complement in disease, there is a requirement for inhibitors to
      control the initiating proteases. In this article, we show that a novel
      inhibitor, gigastasin, from the giant Amazon leech, potently inhibits C1s and
      MASP-2, whereas it is also a good inhibitor of MASP-1. Gigastasin is a poor
      inhibitor of C1r. The inhibitor blocks the active sites of C1s and MASP-2, as
      well as the anion-binding exosites of the enzymes via sulfotyrosine residues.
      Complement deposition assays revealed that gigastasin is an effective inhibitor
      of complement activation in vivo, especially for activation via the lectin
      pathway. These data suggest that the cumulative effects of inhibiting both MASP-2
      and MASP-1 have a greater effect on the lectin pathway than the more potent
      inhibition of only C1s of the classical pathway.

PMID- 29061763
TI  - A TNF-p100 pathway subverts noncanonical NF-kappaB signaling in inflamed
      secondary lymphoid organs.
AB  - Lymphotoxin-beta receptor (LTbetaR) present on stromal cells engages the
      noncanonical NF-kappaB pathway to mediate RelB-dependent expressions of
      homeostatic chemokines, which direct steady-state ingress of naive lymphocytes to
      secondary lymphoid organs (SLOs). In this pathway, NIK promotes partial
      proteolysis of p100 into p52 that induces nuclear translocation of the RelB NF
      kappaB heterodimers. Microbial infections often deplete homeostatic chemokines;
      it is thought that infection-inflicted destruction of stromal cells results in
      the downregulation of these chemokines. Whether inflammation per se also
      regulates these processes remains unclear. We show that TNF accumulated upon non
      infectious immunization of mice similarly downregulates the expressions of these
      chemokines and consequently diminishes the ingress of naive lymphocytes in
      inflamed SLOs. Mechanistically, TNF inactivated NIK in LTbetaR-stimulated cells
      and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently
      accumulated unprocessed p100, which attenuated the RelB activity as inhibitory
      IkappaBdelta. Finally, a lack of p100 alleviated these TNF-mediated inhibitions
      in inflamed SLOs of immunized Nfkb2-/- mice. In sum, we reveal that an inhibitory
      TNF-p100 pathway modulates the adaptive compartment during immune responses.

PMID- 29061766
TI  - Palmitate Conditions Macrophages for Enhanced Responses toward Inflammatory
      Stimuli via JNK Activation.
AB  - Obesity is associated with low-grade inflammation and elevated levels of
      circulating saturated fatty acids, which trigger inflammatory responses by
      engaging pattern recognition receptors in macrophages. Because tissue homeostasis
      is maintained through an adequate balance of pro- and anti-inflammatory
      macrophages, we assessed the transcriptional and functional profile of M-CSF
      dependent monocyte-derived human macrophages exposed to concentrations of
      saturated fatty acids found in obese individuals. We report that palmitate
      (C16:0, 200 MUM) significantly modulates the macrophage gene signature, lowers
      the expression of transcription factors that positively regulate IL-10 expression
      (MAFB, AhR), and promotes a proinflammatory state whose acquisition requires JNK
      activation. Unlike LPS, palmitate exposure does not activate STAT1, and its
      transcriptional effects can be distinguished from those triggered by LPS, as both
      agents oppositely regulate the expression of CCL19 and TRIB3 Besides, palmitate
      conditions macrophages for exacerbated proinflammatory responses (lower IL-10 and
      CCL2, higher TNF-alpha, IL-6, and IL-1beta) toward pathogenic stimuli, a process
      also mediated by JNK activation. All of these effects of palmitate are fatty acid
      specific because oleate (C18:1, 200 MUM) does not modify the macrophage
      transcriptional and functional profiles. Therefore, pathologic palmitate
      concentrations promote the acquisition of a specific polarization state in human
      macrophages and condition macrophages for enhanced responses toward inflammatory
      stimuli, with both effects being dependent on JNK activation. Our results provide
      further insight into the macrophage contribution to obesity-associated
      inflammation.

PMID- 29061768
TI  - Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and
      Fibrosis in Mice.
AB  - Promising results of immune checkpoint inhibitors have indicated the use of
      immunotherapy against malignant tumors. However, they cause serious side effects,
      including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3
      is a new candidate immune checkpoint molecule; however, the potential toxicity
      associated with anti-TIM-3 treatment is unknown. In this study, we investigated
      the pathological contribution of anti-TIM-3 mAb in a bleomycin-induced lung
      inflammation and fibrosis model. Anti-TIM-3-treated mice showed more severe
      inflammation and peribronchiolar fibrosis compared with control IgG-treated mice.
      Anti-TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen
      deposition, and TGF-beta1 production in lungs. TIM-3 expression was only detected
      on alveolar macrophages that protect against fibrosis by apoptotic cell
      clearance. Treatment with anti-TIM-3 mAb inhibited the phagocytic ability of
      alveolar macrophages in vivo, resulting in the defective clearance of apoptotic
      cells in lungs. In summary, anti-TIM-3 mAb treatment might cause pneumonitis and
      it should be used with caution in clinical settings.

PMID- 29061767
TI  - Thymic-Specific Serine Protease Limits Central Tolerance and Exacerbates
      Experimental Autoimmune Encephalomyelitis.
AB  - The genetic predisposition to multiple sclerosis (MS) is most strongly conveyed
      by MHC class II haplotypes, possibly by shaping the autoimmune CD4 T cell
      repertoire. Whether Ag-processing enzymes contribute to MS susceptibility by
      editing the peptide repertoire presented by these MHC haplotypes is unclear.
      Thymus-specific serine protease (TSSP) is expressed by thymic epithelial cells
      and thymic dendritic cells (DCs) and, in these two stromal compartments, TSSP
      edits the peptide repertoire presented by class II molecules. We show in this
      article that TSSP increases experimental autoimmune encephalomyelitis severity by
      limiting central tolerance to myelin oligodendrocyte glycoprotein. The effect on
      experimental autoimmune encephalomyelitis severity was MHC class II allele
      dependent, because the lack of TSSP expression conferred protection in NOD mice
      but not in C57BL/6 mice. Importantly, although human thymic DCs express TSSP,
      individuals segregate into two groups having a high or 10-fold lower level of
      expression. Therefore, the level of TSSP expression by thymic DCs may modify the
      risk factors for MS conferred by some MHC class II haplotypes.

PMID- 29061769
TI  - Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of
      the Neurokinin-1 Receptor System.
AB  - Neuroblastoma is the most common solid extracranial malignant tumor in children.
      Despite recent advances in the treatment of this heterogenous tumor with surgery
      and chemotherapy, the prognosis in advanced stages remains poor. Interestingly,
      neuroblastoma is one of the few solid tumors, to date, in which an effect for
      targeted immunotherapy has been proven in controlled clinical trials, giving hope
      for further advances in the treatment of this and other tumors by targeted
      therapy. A large array of novel therapeutic options for targeted therapy of
      neuroblastoma is on the horizon. To this repepsilonrtoirepsilon, the neurokinin-1
      receptor (NK1R) system was recently added. The present article explores the most
      recent developments in targeting neuroblastoma cells via the NK1R and how this
      new knowledge could be helpful to create new anticancer therapies agains
      neuroblastoma and other cancers.

PMID- 29061770
TI  - Search for New Type of Anticancer Drugs with High Tumor Specificity and Less
      Keratinocyte Toxicity.
AB  - Most current anticancer drugs have shown excellent therapeutic effects on human
      oral squamous cell carcinoma (OSCC), but they also produce potent cytotoxicity in
      normal oral keratinocytes. This review article summarizes our extensive research
      of tumor specificity and keratinocyte toxicity of nine groups of compounds
      synthesized in our laboratory. Among a total of 133 compounds, (E)-3-[2-(4
      hydroxyphenyl)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [3] (classified as 3
      styrylchromones), (E)-3-[2-(4-chlorophenyl)ethenyl]-7-methoxy-2H-1-benzopyran [4]
      (classified as 3-styryl-2H-chromenes) showed the highest tumor specificity with
      the least keratinocyte toxicity. Compound [3] induced apoptotic cell death in a
      human OSCC cell line, possibly by down-regulating the glycerophospholipid
      pathway. Quantitative structure-activity relationship analysis demonstrated that
      the tumor specificities of [3] and [4] were well correlated with chemical
      descriptors related to their molecular size and lipophilicity. Chemical
      modification of these lead compounds by introduction of appropriate functional
      groups is a crucial step towards manufacturing new types of anticancer drugs with
      reduced keratinocyte toxicity.

PMID- 29061771
TI  - A Systematic Review and Meta-analysis of Retrospective Series of Regorafenib for
      Treatment of Metastatic Colorectal Cancer.
AB  - BACKGROUND: Metastatic colorectal cancer is a common disease encountered in
      oncology practice and treatment options beyond fluoropyrimidines, irinotecan,
      oxaliplatin and monoclonal antibodies against epidermal growth factor receptor
      and vascular endothelium growth factor (VEGF) are limited. Regorafenib, a new
      drug that targets tyrosine kinases such as VEGF receptor as well as others, has
      been added recently to the armamentarium for metastatic colorectal cancer. This
      report analyzes the published experience with this drug in clinical practice
      outside of clinical trials. MATERIALS AND METHODS: A literature search of major
      databases was performed for the identification of studies of regorafenib in
      metastatic colorectal cancer. Studies retained for further analysis were in
      English or French, describing 20 or more patients treated with regorafenib
      monotherapy and not part of a phase I, II or III trial. Results of the pooled
      analysis of retrospective studies were compared with results of the published
      phase III trials and a phase IIIb prospective study. RESULTS: Twelve publications
      including a total of 702 patients were included in the meta-analysis. Summary
      response rate was 2% [95% confidence interval (CI) =0.8-3.2%] and the disease
      control rate 38.14% (95% CI=32.35-43.93%). Summary survival rates were 3.34
      months (95% CI=2.71-3.97 months) for progression-free and 7.27 months (95%
      CI=6.23-8.3 months) for overall survival. These were similar to the phase III and
      IIIb studies. Most common adverse effects were also consistent with those of the
      published phase III experience. CONCLUSION: This systematic review and meta
      analysis confirmed a moderate efficacy of regorafenib in later-stage metastatic
      colorectal cancer in the everyday clinical practice setting outside of clinical
      trials. Future identification of biomarkers may aid in further tailoring of this
      treatment in order to obtain maximum clinical benefit.

PMID- 29061765
TI  - CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral
      Immune Responses in Rainbow Trout.
AB  - Chemokines and chemokine receptors have rapidly diversified in teleost fish but
      their immune functions remain unclear. We report in this study that CCL19, a
      chemokine known to control lymphocyte migration and compartmentalization of
      lymphoid tissues in mammals, diversified in salmonids leading to the presence of
      six CCL19-like genes named CK10a, CK10b, CK12a, CK12b, CK13a, and CK13b. Salmonid
      CCL19-like genes all contain the DCCL-conserved motif but share low amino acid
      sequence identity. CK12 (but not CK10 or CK13) is constitutively expressed at
      high levels in all four trout MALT. Nasal vaccination with a live attenuated
      virus results in sustained upregulation of CK12 (but not CK10 or CK13) expression
      in trout nasopharynx-associated lymphoid tissue. Recombinant His-tagged trout
      CK12a (rCK12a) is not chemotactic in vitro but it increases the width of the
      nasal lamina propria when delivered intranasally. rCK12a delivered intranasally
      or i.p. stimulates the expression of CD8alpha, granulysin, and IFN-gamma in
      mucosal and systemic compartments and increases nasal CD8alpha+ cell numbers.
      rCK12a is able to stimulate proliferation of head kidney leukocytes from Ag
      experienced trout but not naive controls, yet it does not confer protection
      against viral challenge. These results show that local nasal production of CK12a
      contributes to antiviral immune protection both locally and systemically via
      stimulation of CD8 cellular immune responses and highlight a conserved role for
      CK12 in the orchestration of mucosal and systemic immune responses against viral
      pathogens in vertebrates.

PMID- 29061772
TI  - Monoclonal Antibodies for the Treatment of Cancer.
AB  - The ability of cancer cells to evade the immune system is one of the most deadly
      characteristics of the majority of malignant tumours. Accordingly, the recent
      development of antibodies which target tumor cell evasion of immune checkpoints
      such as the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as the
      programmed cell death protein (PD-1) and the PD-1 ligand (PD-L1) has been a major
      and apparently highly effective approach in the treatment and/or eradication of a
      variety of highly malignant forms of cancers. The US Food and Drug Administration
      (FDA) has recently approved the application of lpilimumab (which targets CTLA-4)
      and pembrolizumab (targeting PD-1) for the treatment of advanced gastric cancer.
      Indeed, various checkpoint blockade antibodies have been approved or have been
      under clinical investigation. An indication of the renewed interest and
      importance of cancer immunotherapy is that James Allison was awarded the Lasker
      DeBakey Clinical Research Award in 2015 for his discovery that antibody blockade
      of CTLA-4 enhances the immune response to cancer. Further, this discovery has
      stimulated the development of multiple immune checkpoint approaches to the
      treatment of cancer. In addition, a number of monoclonal antibodies (MAB) have
      been created to specifically target antigens on cancer cells and/or to
      selectively deliver radiotherapy to them. These immunotherapeutic approaches and
      advances will be reviewed in this article.

PMID- 29061773
TI  - New Drug Combination Strategies in Melanoma: Current Status and Future
      Directions.
AB  - Melanoma is the deadliest form of skin cancer and one of the most difficult
      cancers to treat. Overall, melanomas have more mutations than any other cancer
      type. Oncogenic mutations in c-KIT, NRAS and BRAF components of the MAPK pathway
      have been identified in nearly 90% of cutaneous melanoma and this information has
      been used to develop small molecules that inhibit their activity. Highly
      selective BRAF and MEK inhibitors have demonstrated impressive clinical results.
      However, the short duration of response, the acquired resistance in most cases
      and the toxicity issues support the rationale for drug combination approaches to
      improve the outcome of MAPK inhibitors, increase their efficacy, prevent and/or
      overcome resistance. This review discusses several promising rational
      combinatorial strategies investigated or could be investigated in clinical
      studies.

PMID- 29061774
TI  - Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and
      Perspectives of Clinical Research.
AB  - The presence of tumor infiltrating lymphocytes (TILs) influences the clinical
      outcome of cancer patients and immune checkpoint inhibitors (ICPI) have been
      approved for treating different types of malignancies. In this review, we assess
      the scanty data from literature and the perspectives of clinical research about
      the use of ICPI in gynecological cancers. These agents have obtained objective
      response rates ranging from 5.9% to 15% in early phase Ib-II trials, including
      patients with platinum-resistant ovarian cancer, whereas only anecdotal data are
      available for patients with recurrent, heavily pretreated endometrial cancer.
      Several ongoing trials are investigating ICPI alone or in combination with
      chemotherapy or with other biological agents in untreated and recurrent ovarian
      cancer, advanced and recurrent endometrial cancer, as well as advanced and
      recurrent cervical cancer. Breast cancer (BRCA)-mutated high-grade serous ovarian
      cancers, clear cell ovarian cancers with microsatellite instability (MSI), POLE
      ultramutated and MSI hypermutated endometrial cancers are likely to be sensitive
      to programmed cell death (PD-1)/PD-ligand 1 (PD-L1) pathway blockade, since these
      tumors show increased neoantigen load, increased CD8+ TIL number and PD-1 and PD
      L1 overexpression. ICPI could have a role as maintenance treatment in patients
      with persistent, recurrent or metastatic cervical cancer in response after
      chemotherapy.

PMID- 29061775
TI  - Perioperative Administration of Traditional Japanese Herbal Medicine Daikenchuto
      Relieves Postoperative Ileus in Patients Undergoing Surgery for Gastrointestinal
      Cancer: A Systematic Review and Meta-analysis.
AB  - AIM: Although it has been widely demonstrated that administration of Daikenchuto
      (DKT), a traditional Japanese herbal medicine, improves gastrointestinal (GI)
      motility in patients undergoing abdominal surgery, few studies have investigated
      the efficacy of perioperative DKT administration for relief of postoperative
      ileus (PI) in patients undergoing surgery for GI cancer. Therefore, the aim of
      this study was to investigate whether perioperative administration of DKT
      relieves PI in patients with GI cancer. PATIENTS AND METHODS: We performed a
      comprehensive electronic search of the literature (Cochrane Library, PubMed, the
      Web of Science and ICHUSHI) up to December 2016 to identify studies that had
      shown the efficacy of perioperative DKT administration for relief of PI in
      patients with GI cancer. To integrate the individual effect of DKT, a meta
      analysis was performed using random-effects models to calculate the risk ratio
      (RR) and 95% confidence interval (CI), and heterogeneity was analyzed using I2
      statistics. RESULTS: Seven studies involving a total of 1,134 patients who had
      undergone GI cancer surgery were included in this meta-analysis. Among 588
      patients who received DKT perioperatively, 67 (11.4%) had PI, whereas among 546
      patients who did not receive DKT perioperatively, 87 (15.9%) had PI.
      Perioperative administration of DKT significantly reduced the occurrence of PI
      (RR=0.58, 95% CI=0.35-0.97, p=0.04, I2=48%) in comparison to patients who did not
      receive DKT or received placebo. CONCLUSION: The result of this meta-analysis
      suggests that perioperative administration of DKT relieves PI in patients
      undergoing surgery for GI cancer.

PMID- 29061776
TI  - Update on Nanotechnology-based Drug Delivery Systems in Cancer Treatment.
AB  - The emerging field of nanotechnology meets the demands for innovative approaches
      in the diagnosis and treatment of cancer. The nanoparticles are biocompatible and
      biodegradable and are made of a core, a particle that acts as a carrier, and one
      or more functional groups on the core which target specific sites. Nanotech in
      drug delivery includes nanodisks, High Density Lipoprotein nanostructures,
      liposomes, and gold nanoparticles. The fundamental advantages of nanoparticles
      are: improved delivery of water-insoluble drugs, targeted delivery, co-delivery
      of two or more drugs for combination therapy, and visualization of the drug
      delivery site by combining imaging system and a therapeutic drug. One of the
      potential applications of nanotechnology is in the treatment of cancer.
      Conventional methods for cancer treatments have included chemotherapy, surgery,
      or radiation. Early recognition and treatment of cancer with these approaches is
      still challenging. Innovative technologies are needed to overcome multidrug
      resistance, and increase drug localization and efficacy. Application of
      nanotechnology to cancer biology has brought in a new hope for developing
      treatment strategies on cancer. In this study, we present a review on the recent
      advances in nanotechnology-based approaches in cancer treatment.

PMID- 29061777
TI  - Possible Biological and Clinical Applications of Phenothiazines.
AB  - Phenothiazines have been used in many areas of medicine, mainly in
      psychopharmacology. These compounds are able to effectively inhibit dopamine,
      histamine, serotonin, acetylcholine, and alpha-adrenergic receptors; thus, their
      effect and side-effect profiles are extremely diverse. Besides their
      antipsychotic activity, phenothiazines have a significant antimicrobial effect as
      well, since they can enhance the bactericidal function of macrophages and inhibit
      efflux pumps. They are also able to eliminate bacterial resistance plasmids and
      destroy bacteria by their membrane-destabilizing effect. Their antiviral,
      antiprotozoal, antifungal, and antiprion activities have also been described.
      Phenothiazines have also been proven to destroy cancer cells and sensitize them
      to chemotherapy. Anti-angiogenesis and anticancer stem cell activities have also
      been reported, and they might be applied as adjuvants in the treatment of
      infections and tumors in the future. Finally, phenothiazines can also be
      effective in the treatment of neurodegenerative diseases, such as Alzheimer's
      disease and Parkinson's disease.

PMID- 29061778
TI  - Anticancer Activity of Artemisinin and its Derivatives.
AB  - Artemisinin is an extract from the plant Artemisia annua. With its semi-synthetic
      derivatives, they form a group of well-known and efficacious antimalarial drugs.
      Recent studies have documented the potential anticancer effect of artemisinin and
      its derivatives (ARTs). This review summarizes results of preclinical studies,
      documenting mechanisms of anticancer actions of ARTs and clinical studies focused
      mainly on efficacy, safety and dose-ranging of ARTs as anticancer
      chemotherapeutics. The main mechanisms of action of ARTs is the production of
      reactive oxygen species, inhibition of cell cycle in G0/G1 phase, induction of
      apoptosis and inhibition of angiogenesis. Safety studies have shown no evident
      toxicity and low incidence of adverse effects. ARTs potential to inhibit growth
      of solid tumours suggests their application in a neoadjuvant therapy.
      Dihydroartemisinin and artesunate exhibit chemosensitising effects in vivo in
      breast, lung, pancreas and glioma cancer cells, proposing the use of ARTs also in
      combination anticancer therapy.

PMID- 29061780
TI  - Docosahexaenoic Acid Monoglyceride Increases Carboplatin Activity in Lung Cancer
      Models by Targeting EGFR.
AB  - BACKGROUND/AIM: Omega 3 polyunsaturated fatty acids (PUFAs) have been shown to
      inhibit the induction and progression of many tumor types. The aim of this study
      was to determine the anticancer effect of docosahexaenoic acid monoglyceride (MAG
      DHA) alone and in combination with the chemotherapeutic agent carboplatin (CBT)
      on lung cancer models. MATERIALS AND METHODS: Adenocarcinoma cell lines A549 and
      H1299 were used to evaluate the effect of combined MAG-DHA and CBT treatments
      both in vitro and in vivo in xenograft models. RESULTS: MAG-DHA+CBT treatment
      decreased cell proliferation and invasion abilities of A549 and H1299 cells.
      Furthermore, MAG-DHA+CBT treatment resulted in a decreased activation of
      epithelial growth factor receptor (EGFR) and its downstream extracellular signal
      regulated kinase (ERK) in cell lysates. In A549 and H1299 xenograft mouse models,
      MAG-DHA+CBT treatment reduced tumor growth. CONCLUSION: Combined MAG-DHA and CBT
      treatment inhibited tumor growth by suppressing EGFR and ERK signaling pathways
      in lung carcinoma cells.

PMID- 29061779
TI  - Identification of 7,8-Diacetoxy-3-Arylcoumarin Derivative as a Selective
      Cytotoxic and Apoptosis-inducing Agent in a Human Prostate Cancer Cell Line.
AB  - BACKGROUND/AIM: Coumarins are a member of the benzopyrone family of compounds
      with diverse and interesting pharmacological properties. In the present study, we
      report the in vitro cytotoxicity evaluation of 7,8-Diacetoxy-3-arylcoumarin
      derivatives (5a-h) in human prostate (PC-3) and breast (MDA-MB-231) cancer cell
      lines. MATERIALS AND METHODS: The cytotoxic activity was evaluated using crystal
      violet dye-binding assay. Furthermore, the most active compound in vitro
      cytotoxic activity in human non-cancerous cell line and its effect on the cell
      cycle phases, apoptosis proteins expression, mitochondrial membrane potential
      (MMP), reactive oxygen species (ROS) production and Glutathione (GSH) level were
      performed. RESULTS: Among the eight compounds that were evaluated, 7,8-Diacetoxy
      3-(4-methylsulfonyl phenyl)coumarin (5f) was the most active derivative with
      highest cytotoxic activity and selectivity against the PC-3 cell line vs. the non
      cancerous WPE1-N22 cell line. The cytotoxic action of compound 5f in PC-3 cells
      is associated with the cell-cycle arrest at -G0/G1 phase, apoptosis, loss in
      mitochondrial membrane potential (MMP), induced reactive oxygen species (ROS)
      production and depletion of Glutathione (GSH) level. CONCLUSION: The result
      indicates that the presence of p-methylsulfonylphenyl group on compound 5f is
      critical in modulating selective cytotoxic activity and induction of apoptosis
      via the mitochondrial apoptotic signaling pathway that is independent of
      cytochrome c release.

PMID- 29061781
TI  - Probing the Oncolytic and Chemosensitizing Effects of Dihydrotanshinone in an In
      Vitro Glioblastoma Model.
AB  - BACKGROUND: Temozolomide is the primary chemotherapeutic agent used to treat
      glioblastoma. However, many tumors are initially resistant to or develop
      resistance to temozolomide, mainly due to high levels of O6-methylguanine DNA
      transferase (MGMT) which repairs DNA damage traditionally caused by temozolomide.
      Dihydrotanshinone (DHT) is extracted from Salvia miltiorrhiza, a Chinese
      medicinal plant, and has also been shown to have antiproliferative effects on
      various cancer cell lines. DHT has been to shown to induce apoptosis via
      induction endoplasmic reticulum stress, that can reportedly sensitize cells to
      temozolomide. MATERIALS AND METHODS: MTS cellular proliferation assays or trypan
      blue viability assays were used to determine the effects of DHT/temozolomide
      combinatorial treatment. Enzyme-linked immunosorbent assay (ELISA) was used to
      determine effects on MGMT and P-glycoprotein levels after singular and
      combinatorial treatment. RESULTS: DHT had a synergistic oncolytic effect in a
      MGMT-deficient cell line and a sensitizing effect in a MGMT-expressing cell line.
      Cytotoxicity due to DHT was shown to be reactive oxygen species-dependent, while
      the combinatorial effect of DHT and temozolomide synergistically reduced MGMT and
      P-glycoprotein levels. CONCLUSION: DHT was shown to augment temozolomide
      efficacy, indicating that, since DHT can penetrate the blood-brain barrier,
      temozolomide in combination with DHT may represent a promising therapeutic option
      for glioblastoma.

PMID- 29061782
TI  - Development and In Vitro Characterization of a Gemcitabine-loaded MUC4-targeted
      Immunoliposome Against Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND/AIM: Pancreatic Ductal adeno-carcinoma (PDAC) is a devastating
      disease. Gemcitabine is the standard chemotherapeutic agent against PDAC but has
      only limited effectiveness. The aim of the study was to develop and study the
      targeting affinity and in vitro antiproliferative effect of a MUC4-targeted
      gemcitabine-loaded immuno-liposome for treatment of PDAC. MATERIALS AND METHODS:
      Gemcitabine-loaded immunoliposomes were developed by grafting anti-MUC4
      antibodies to the liposomal surface. Targeting affinity was compared in vitro
      between immunoliposomes and non-targeted liposomes and anti-proliferative effect
      was compared in vitro between free drug, non-targeted liposomal gemcitabine and
      MUC4-targeted immunoliposomal gemcitabine on a MUC4-positive pancreatic cancer
      cell line, Capan-1. RESULTS: Development of a MUC4-targeted immunoliposome was
      confirmed and characterized by immunoblots and size characterization. The MUC4
      targeted immunoliposome showed a significantly higher targeting affinity compared
      to the non-targeted liposomes and also showed an improved antiproliferative
      effect compared to free and non-targeted liposomal drug. CONCLUSION: Successful
      development and characterization of a MUC4-targeted immunoliposome shows
      promising results for a targeted treatment and improved retention of gemcitabine
      for treatment of PDAC.

PMID- 29061783
TI  - Fucoidans Stimulate Immune Reaction and Suppress Cancer Growth.
AB  - BACKGROUND/AIM: Fucoidans are gaining popularity as natural immunomodulators. The
      aim of this study was to compare the immunological activities or both purified
      samples and commercially available mixtures containing fucoidan. MATERIALS AND
      METHODS: We evaluated the effects of various samples on phagocytosis, mitogenic
      response, natural killer (NK) activity, antibody formation and inhibition of
      breast cancer growth. RESULTS: We found significant immunostimulating activity,
      but the strength of these effects was different among individual samples.
      CONCLUSION: Fucoidans have strong immunostimulating potential, including
      inhibition of cancer, with isolated samples offering better activity than
      commercial mixtures.

PMID- 29061784
TI  - BMI1 Inhibitors Down-regulate NOTCH Signaling and Suppress Proliferation of Acute
      Leukemia Cells.
AB  - BACKGROUND/AIM: B cell-specific Moloney murine leukemia virus integration site 1
      (BMI1) is up-regulated in several cancers; therefore, we investigated the effects
      of BMI1 inhibitors on leukemia cells. MATERIALS AND METHODS: Four acute myeloid
      leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1
      inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation
      and gene expression by microarray and immunoblotting. RESULTS: PTC-209 and
      PRT4165 suppressed the growth of all cell lines through apoptosis.Artemisinin
      acted only on Jurkat cells. BMI1 inhibitors and BMI1-specific siRNA down
      regulated the expression of NOTCH signaling proteins NOTCH1, HES1, and MYC. All
      but one cell lines did not have the cyclin-dependent kinase inhibitor 2A (CDKN2A)
      gene targeted by BMI1, thus the inhibitors acted through CDKN2A-independent
      pathways. CONCLUSION: BMI1 inhibition suppressed proliferation of leukemia cells
      through NOTCH signaling which functions downstream of BMI1, suggesting that BMI1
      inhibitors can be candidate targeted drugs against leukemia.

PMID- 29061785
TI  - Cisplatin-loaded, Sialyl Lewis X-Modified Liposomes: Drug Release,
      Biodistribution and Antitumor Efficacy.
AB  - BACKGROUND/AIM: The aim of this study was to evaluate the characteristics of two
      cisplatin (CDDP)-loaded, sialyl Lewis X-modified liposomes (CDDP-SLX-LIP) with
      different particle size. Each had the same lipid composition and CDDP
      concentration, but a different drug-to-lipid ratio. MATERIALS AND METHODS: The
      amount of platinum in the filtrates was determined by the ICP method. The
      antitumor effect was assessed using rats bearing MRMT-1 tumor. RESULTS: CDDP
      release was faster from the larger liposome formulation (L-LIP) than from the
      smaller one (S-LIP). Treatment with the two CDDP-SLX-LIPs resulted in comparable
      antitumor effects without obvious side-effects, but treatment with CDDP solution
      resulted in significant weight loss and an elevated BUN. Tumor accumulation of
      CDDP-SLX-LIP was clearly greater than that of CDDP solution and accumulation of S
      LIP was greater than that of L-LIP. CONCLUSION: CDDP-SLX-LIP exhibited antitumor
      effects depending on their release behavior and tumor accumulation.

PMID- 29061786
TI  - Pirarubicin, an Anthracycline Anticancer Agent, Induces Apoptosis Through
      Generation of Hydrogen Peroxide.
AB  - BACKGROUND/AIM: Pirarubicin (THP) has shown equal or superior cytotoxicity
      compared to doxorubicin. One of the main anticancer actions of doxorubicin is
      believed to be involved in ROS (reactive oxygen species) generation. Therefore,
      the anticancer mechanisms of THP may involve ROS generation. The aim of this
      study was to clarify the mechanisms of THP-induced apoptosis through ROS
      generation. MATERIALS AND METHODS: We analyzed the apoptotic events induced by
      THP in HL-60 cells and HP100 cells, hydrogen peroxide (H2O2)-resistant cells
      derived from HL-60. RESULTS: The apparent cytotoxicity could be detected at above
      0.1 MUM in HL-60 cells after 24-h incubation, whereas it was suppressed under
      these conditions in HP100 cells. In HP100 cells, THP-induced apoptosis, evaluated
      by DNA ladder formation, H2O2 generation, mitochondrial membrane potential
      decrease and caspase-3/7 activity, was suppressed or delayed compared to those of
      HL-60 cells. CONCLUSION: These findings can be explained by the involvement of
      H2O2 generation in the THP apoptotic pathway. This is the first report on THP
      induced apoptosis through the H2O2 generation.

PMID- 29061787
TI  - (-)-Epigallocatechin-3-gallate Down-regulates Doxorubicin-induced Overexpression
      of P-glycoprotein Through the Coordinate Inhibition of PI3K/Akt and MEK/ERK
      Signaling Pathways.
AB  - BACKGROUND/AIM: (-)-Epigallocatechin-3-gallate (EGCG) has been indicated to
      regulate the function of P-glycoprotein (P-gp), which is a drug transporter
      encoded by the MDR1 (ABCB1) gene. P-gp expression is induced by doxorubicin
      (DOX). We aimed to clarify the mechanisms and inhibitory effects of EGCG on DOX
      induced P-gp expression in HepG2 cells. MATERIALS AND METHODS: Rhodamine 123
      (Rho123) was used for P-gp substrate. Western blotting and polymerase chain
      reactions (PCRs) were conducted using specific antibodies and primer sets.
      RESULTS: The DOX-pretreated cells accumulated a significantly decreased amount of
      Rho123), than control cells; however, the cells pretreated with EGCG and DOX, in
      combination, accumulated Rho123 more than DOX-pretreated cells. DOX induced the
      overexpression of MDR1 mRNA and increased the phosphorylation of Akt, ERK1/2, p38
      MAPK and JNK. EGCG significantly inhibited the phosphorylation of Akt and ERK.
      The DOX-induced P-gp overexpression was partially suppressed by an inhibitor of
      MEK1/2 (U0126), but not by a PI3K inhibitor (LY294002). Interestingly, the
      expression of P-gp was synergistically inhibited by combined treatment of U0126
      with LY294002 and also inhibited by an mTORC1 inhibitor, rapamycin. CONCLUSION:
      EGCG inhibited DOX-induced overexpression of P-gp through the coordinate
      inhibitory action on MEK/ERK and PI3K/Akt signaling pathways.

PMID- 29061788
TI  - Expression of Truncated Neurokinin-1 Receptor in Childhood Neuroblastoma is
      Independent of Tumor Biology and Stage.
AB  - BACKGROUND: Neuroblastoma is an embryonal malignancy arising from the aberrant
      growth of neural crest progenitor cells of the sympathetic nervous system. The
      tachykinin receptor 1 (TACR1) - substance P complex is associated with tumoral
      angiogenesis and cell proliferation in a variety of cancer types. Inhibition of
      TACR1 was recently described to impede growth of NB cell lines. However, the
      relevance of TACR1 in clinical settings is unknown. PATIENTS AND METHODS: We
      investigated gene expression levels of full-length and truncated TACR1 in 59
      neuroblastomas and correlated these data with the patients' clinical parameters
      such as outcome, metastasis, International Neuroblastoma Staging System (INSS)
      status, MYCN proto-oncogene, bHLH transcription factor (MYCN) status, gender and
      age. RESULTS: Our results indicated that TACR1 is ubiquitously expressed in
      neuroblastoma but expression levels are independent of clinical parameters.
      CONCLUSION: Our data suggest that TACR1 might serve as a potent anticancer target
      in a large variety of patients with neuroblastoma, independent of tumor biology
      and clinical stage.

PMID- 29061789
TI  - Changes in the Lysosomal System of Cervical Cancer Cells Induced by Emodin
      Action.
AB  - BACKGROUND: An example of plant-derived compounds that may be of great importance
      in oncological therapy is emodin. The aim of this study was to evaluate the range
      of changes in the lysosomal compartment of HeLa cervical cancer cells treated
      with emodin. MATERIALS AND METHODS: Changes in the lysosomal compartment were
      evaluated using microscopic techniques. In order to evaluate the activity of
      lysosomal enzymes and the permeability of the lysosomal membrane, a
      spectrophotometric technique was employed. RESULTS: Emodin induced significant
      changes in the lysosomal compartment, manifesting as an increase in the number of
      lysosomes, autophagic vacuoles and the activity of lysosomal hydrolases. Emodin
      exhibited cytotoxic activity against lysosomes through lysosomal membrane damage
      with possible leaks of lysosomal hydrolases into the cytoplasm. CONCLUSION:
      Emodin induces degradation processes and promotes the death of tumor cells
      through a mechanism that occurs with clear involvement of the lysosomal
      compartment.

PMID- 29061790
TI  - Synergistic Effects of a Smac Mimetic with Doxorubicin Against Human
      Osteosarcoma.
AB  - BACKGROUND/AIM: Second mitochondria-derived activator of caspase (Smac) is a
      proapoptogenic mitochondrial protein that antagonizes inhibitors of apoptosis
      proteins (IAPs), resulting in induction of apoptosis. In the present study we
      investigated the effects of a Smac mimetic in combination with doxorubicin
      against osteosarcoma. MATERIALS AND METHODS: In vitro effects of the combination
      of a Smac mimetic AT-406 and doxorubicin on cell proliferation and apoptosis in
      osteosarcoma cell lines were examined using cell proliferation assays, flow
      cytometry, and immunoblot analyses. For in vivo experiments, human osteosarcoma
      xenografts were treated with combination of the two substances, and tumor volume
      and apoptotic activity in treated tumors were assessed. RESULTS: In vitro studies
      revealed that combination of the two substances significantly inhibited
      osteosarcoma proliferation with decreased cIAP1 expression and induced apoptosis
      in osteosarcoma cells. Combination of the two substances significantly suppressed
      osteosarcoma growth in vivo. Moreover, decreased cIAP1 expression and increased
      apoptotic activity were observed in tumors treated by their combination of the
      substances. CONCLUSION: The Smac mimetic AT-406 showed an apoptotic effect and a
      synergistic antitumor effect with doxorubicin on osteosarcoma. The combination of
      AT-406 and doxorubicin may serve as a novel therapeutic strategy for osteosarcoma
      treatment.

PMID- 29061792
TI  - Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma.
AB  - BACKGROUND/AIM: The neurokinin 3 receptor (NK-3R) is differentially expressed in
      the central nervous system including cases of human oral squamous cell carcinoma.
      However, the role of NK-3R signaling in oral squamous cell carcinoma is not well
      known. MATERIALS AND METHODS: NK-3R expression in surgically resected oral
      squamous cell carcinoma was examined immunohistochemically and the strength of
      the expression was quantified. We evaluated the function of NK-3R signaling using
      NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model.
      RESULTS: NK-3R was significantly expressed in tumor cells that had invaded the
      bone matrix compared to the oral side tumor cells. SB222200, a selective
      antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion
      and tumorigenesis. CONCLUSION: NK-3R signaling is a potential target for the
      treatment of oral squamous cell carcinoma in cases of bone destruction.

PMID- 29061791
TI  - Tetrandrine Induces Apoptosis in Human Nasopharyngeal Carcinoma NPC-TW 039 Cells
      by Endoplasmic Reticulum Stress and Ca2+/Calpain Pathways.
AB  - Tetrandrine is an alkaloid extracted from a traditional China medicine plant, and
      is considered part of food therapy as well. In addition, it has been widely
      reported to induce apoptotic cell death in many human cancer cells. However, the
      mechanism of Tetrandrine on human nasopharyngeal carcinoma cells (NPC) is still
      questioned. In our study, we examined whether Tetrandrine can induce apoptosis of
      NPC-TW 039 cells. We found that cell morphology was changed after treatment with
      different concentrations of Tetrandrine. Further, we indicated that the NPC-TW
      039 cells viability decreased in a Tetrandrine dose-dependent manner. We also
      found that tetrandrine induced cell cycle arrest in G0/G1 phase. Tetrandrine
      induced DNA condensation by DAPI staining as well. In addition, we found that
      Tetrandrine induced Ca2+ release in the cytosol. At the same time, endoplasmic
      reticulum (ER) stress occurred. Then we used western blotting to examine the
      protein expression which is associated with mitochondria-mediated apoptotic
      pathways and caspase-dependent pathways. To further examine whether Ca2+ was
      released or not with Tetrandrine induced-apoptosis, we used the chelator of Ca2+
      and showed that cell viability increased. At the same time, caspase-3 expression
      was decreased. Furthermore, confocal microscopy examination revealed that
      Tetrandrine induced expression of ER stress-related proteins GADD153 and GRP78.
      Our results indicate that Tetrandrine induces apoptosis through calcium-mediated
      ER stress and caspase pathway in NPC-TW 039 cells. In conclusion, Tetrandrine may
      could be used for treatment of human nasopharyngeal carcinoma in future.

PMID- 29061794
TI  - Trehalose Liposomes Suppress the Growth of Tumors on Human Lung Carcinoma-bearing
      Mice by Induction of Apoptosis In Vivo.
AB  - BACKGROUND/AIM: Previous evidence demonstrates that trehalose liposomes
      (DMTreC14) composed of L-alpha-dimyristoylphosphatidylcholine (DMPC) and alpha-D
      glycopyranosyl-alpha-D-glucopyranoside monomyristate (TreC14) inhibit
      proliferation and invasion on lung carcinoma (A549 cells) in vitro. Here, we
      aimed to investigate suppressive effects of DMTreC14 on the growth of tumor on
      human lung carcinoma bearing mice. MATERIALS AND METHODS: DMTreC14 composed of 30
      mol% DMPC and 70 mol% TreC14 were prepared by the sonication method. Anti-tumor
      activities of DMTreC14 using the subcutaneous and orthotopic graft-bearing mice
      of A549 cells were investigated in vivo. RESULTS: The remarkable reduction of
      volume and weight in subcutaneous tumors on subcutaneous lung carcinoma-bearing
      mice topically administrated with DMTreC14 were obtained. Apoptotic-positive
      cells in the subcutaneous tumor slice of subcutaneous lung carcinoma-bearing mice
      topically administrated with DMTreC14 were observed using TUNEL staining. Lung
      weights on the orthotopic graft-bearing mice of lung carcinoma intravenously
      administrated with DMTreC14 were markedly decreased compared to those of the
      control group. Remarkable decrease in dimensions of tumor area of lung on the
      orthotopic graft-bearing mice of lung carcinoma intravenously administrated with
      DMTreC14 was obtained in histological analysis using the hematoxylin and eosin
      staining. CONCLUSION: Remarkably high anti-tumor activities of DMTreC14 for the
      subcutaneous and orthotopic graft-bearing mice of lung carcinoma accompanied with
      apoptosis were revealed for the first time in vivo.

PMID- 29061793
TI  - The Anti-tumor Effect of Cabozantinib on Ovarian Clear Cell Carcinoma In Vitro
      and In Vivo.
AB  - BACKGROUND: Several reports have shown that the overexpression of the MET proto
      oncogene, receptor tyrosine kinase (MET), was more frequently observed in clear
      cell carcinoma (CCC) than in non-CCC. We evaluated the antitumor activity of
      cabozantinib, that targets MET. MATERIALS AND METHODS: A gene expression analysis
      of tumors from human ovarian cancers was carried out by transcriptome sequencing.
      An in vitro 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay
      (MTT assay) and in vivo experiments were performed to determine the activity of
      cabozantinib. RESULTS: The MET levels were higher in tumors with CCC than high
      grade serous carcinoma (2.2-fold). Cabozantinib inhibited cell viability and
      phosphorylation of AKT and MAPK under the treatment of hepatocyte growth factor
      in RMG-I CCC cells. The tumors removed from mice given cabozantinib of 10 mg/kg
      weighed 70% less than control on day 15, and the immunohistochemical reactivity
      of phosphorylated MET was reduced compared with control mice. CONCLUSION:
      Cabozantinib contributes to tumor reduction, and phosphorylated MET represents an
      attractive target of CCC.

PMID- 29061795
TI  - Berberine and Evodiamine Act Synergistically Against Human Breast Cancer MCF-7
      Cells by Inducing Cell Cycle Arrest and Apoptosis.
AB  - BACKGROUND/AIM: The synergistic combinations of natural products have long been
      the basis of Traditional Chinese herbal Medicine formulas. In this study, we
      investigated the synergistic effects of a combination of berberine and evodiamine
      against human breast cancer MCF-7 cells in vitro and in vivo, and explored its
      mechanism. MATERIALS AND METHODS: Cell survival was measured using the MTT assay.
      Apoptosis-related proteins were observed using western blot analysis. Apoptosis
      was detected with flow cytometric analysis and by Hoechst 33258 staining. Tumor
      xenografts were used in vivo. RESULTS: Compared to berberine or evodiamine
      treatments alone, the combination treatment of berberine (25 MUM) and evodiamine
      (15 MUM) synergistically inhibited the proliferation of MCF-7 cells in a time
      dependent manner and resulted in the G0/G1 phase accumulation of cells that
      exhibited increased expression levels of the CDK inhibitors p21 and p27 with a
      concomitant reduction in the expression levels of cell-cycle checkpoint proteins
      cyclin D1, cyclin E, CDK4, and CDK6. Furthermore, the combination treatment
      induced apoptosis that was accompanied by increased expression levels of p53 and
      Bax, reduced expression levels of Bcl-2, activation of caspase-7, and caspase-9,
      and the cleavage of PARP. The combination of berberine and evodiamine
      synergistically inhibited tumor growth in vivo in MCF-7 human breast cancer
      xenografts. CONCLUSION: Combination of berberine and evodiamine acts
      synergistically to suppress the proliferation of MCF-7 cells by inducing cell
      cycle arrest and apoptosis, illustrating the potential synergistic and
      combinatorial application of bioactive natural products.

PMID- 29061796
TI  - Differential Anticancer Activity of Pterostilbene Against Three Subtypes of Human
      Breast Cancer Cells.
AB  - Although pterostilbene, a natural analog of resveratrol, has potent antitumor
      activity against several human cancer types, the possible inhibitory mechanisms
      against subtypes of human breast cancer with different hormone receptor and human
      epidermal growth factor receptor 2 (HER2) status remain unknown. We investigated
      the anticancer activity of pterostilbene using three subtypes of breast cancer
      cell lines. Pterostilbene treatment exhibited a dose-dependent antiproliferative
      activity, with the greatest growth inhibition observed in triple-negative MDA-MB
      468 cells. Although pterostilbene arrested cell-cycle progression at the G0/G1
      phase regardless of breast cancer subtype, its apoptosis-inducing activity was
      highly apparent in MDA-MB-468 cells. Pterostilbene induced strong and sustained
      activation of extracellular signal-regulated kinase (ERK) 1/2, with concomitant
      cyclin D1 suppression and p21 up-regulation, and inhibited the phosphorylation of
      AKT and mammalian target of rapamycin (mTOR), followed by subsequent up
      regulation of BAX without affecting B-cell lymphoma-extra large (BCL-xL). Oral
      administration of pterostilbene significantly suppressed tumor growth in nude
      mice xenotransplanted with MDA-MB-468 cells. These data suggest a potential role
      of pterostilbene for prevention and treatment of human breast cancer, especially
      of triple-negative breast cancer.

PMID- 29061797
TI  - Quantitative Structure-Cytotoxicity Relationship of Newly Synthesized Piperic
      Acid Esters.
AB  - BACKGROUND/AIM: Eleven piperic acid esters were subjected to quantitative
      structure-activity relationship (QSAR) analysis based on their cytotoxicity and
      tumor-specificity, in order to find their new biological activities. MATERIALS
      AND METHODS: Cytotoxicity against four human oral squamous cell carcinoma cell
      lines and three oral normal mesenchymal cells was determined by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor
      specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic
      concentration (CC50) against normal cells to that against tumor cell lines.
      Potency-selectivity expression (PSE) value was calculated by dividing the TS
      value by CC50 against tumor cells. Apoptosis markers were detected by western
      blot analysis. Physicochemical, structural and quantum-chemical parameters were
      calculated based on the conformations optimized by force-field minimization.
      RESULTS: One phenylmethyl ester and five phenylethyl esters showed relatively
      higher cytotoxicity and tumor specificity, that were significantly modified by
      introduction of hydroxyl and methoxy groups. On the other hand, phenylpropyl
      ester, phenylbutyl ester and decyl ester were essentially inactive. (2E,4E)-5
      (3,4-methylenedioxyphenyl)-2,4-pentadienoic acid 2-(3,4-dihydroxyphenyl)ethyl
      ester [4] had the highest TS and PSE values. This compound also stimulated the
      cleavage of caspase-3, suggesting the induction of apoptosis. TS values were
      correlated with molecular size, ionization potential, molecular shape, ionization
      potential and electronegativity. None of the compounds had any anti-HIV activity.
      CONCLUSION: Chemical modification of the lead compound may be a potential choice
      for designing a new type of anticancer drugs.

PMID- 29061798
TI  - Quantitative Structure-Cytotoxicity Relationship of Aurones.
AB  - BACKGROUND/AIM: Seventeen aurones were subjected to quantitative structure
      activity relationship (QSAR) analysis based on their cytotoxicity and tumor
      specificity, in order to find their new biological activities. MATERIALS AND
      METHODS: Cytotoxicity against three human oral squamous cell carcinoma cell lines
      and three oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was
      evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against
      normal cells to that against tumor cell lines. Potency-selectivity expression
      (PSE) value was calculated by dividing TS by CC50 against tumor cells.
      Physicochemical, structural and quantum-chemical parameters were calculated based
      on the conformations optimized by force-field minimization. RESULTS: Sixteen out
      of seventeen aurones showed relatively higher cytotoxicity and tumor specificity.
      Among them, (2Z)-2-[(4-hydroxyphenyl)methylene]-3(2H)-benzofuranone [7] showed
      the highest TS value and PSE values, comparable with those of doxorubicin and
      higher than 5-FU, respectively. TS values were correlated with molecular shape,
      size and polarizability rather than the types of substituted groups. CONCLUSION:
      Chemical modification of the lead compound may be a potential choice for
      designing a new type of anticancer drugs.

PMID- 29061799
TI  - Olanzapine, an Atypical Antipsychotic, Inhibits Survivin Expression and
      Sensitizes Cancer Cells to Chemotherapeutic Agents.
AB  - BACKGROUND/AIM: Olanzapine, an atypical antipsychotic, is now increasingly used
      as an off-label indication for the management of cancer patients with
      chemotherapy-induced nausea and vomiting (CINV). However, how olanzapine affects
      cancer cells per se remains poorly understood. MATERIALS AND METHODS: The effects
      of olanzapine treatment and survivin knockdown, alone or in combination with
      chemotherapeutic agents, on survivin expression and cell viability were
      investigated in human cancer cell lines. RESULTS: Olanzapine reduced survivin
      expression in lung and pancreatic cancer stem cell (CSC) lines and sensitized
      them to chemotherapeutic agents such as 5-fluorouracil, gemcitabine, and
      cisplatin in a survivin expression-dependent manner. Olanzapine also reduced
      survivin expression and chemosensitized serum-cultured, non-CSC ovarian cancer
      cells that expressed survivin. CONCLUSION: Olanzapine may benefit cancer patients
      not only as an antiemetic for CINV, but also by enhancing the effects of
      chemotherapeutic agents through down-regulation of survivin, which has been
      implicated in multidrug chemoresistance.

PMID- 29061801
TI  - A Simple Method to Optimize the Effectiveness of Chemotherapy: Modulation of
      Glucose Intake During Chemotherapy.
AB  - BACKGROUND/AIM: Cancer cells consume high amounts of glucose to produce ATP and
      molecules entering biosynthesis. Numerous experimental studies have demonstrated
      that glucose deprivation and/or glycolysis inhibition arrest cancer cell growth
      and may increase the efficiency of cytotoxic drugs. In contrast, increasing
      glycolysis in tumor-infiltrating lymphocytes (TILs) activates these cells that
      destroy cancer cells. We propose to increase the efficiency of chemotherapy by
      modulating glucose intake during the course of chemotherapy. MATERIALS AND
      METHODS: Glucose and caloric intake should be drastically reduced the day before
      and during chemotherapy administration to deprive cancer cells of ATP and
      molecules required to repair cytotoxic lesions. Few hours after chemotherapy,
      glucose and caloric intake should be drastically increased for few days to
      promote the activation of TILs that reinforce the destruction of cancer cells.
      RESULTS: This strategy could improve the results of chemotherapy by first
      enhancing cytotoxic stress against tumor cells and then promoting activation of
      the anti-cancer immune response. CONCLUSION: The modulation of glucose intake
      during chemotherapy should be tested clinically. The proposed scheme is simple,
      surely easier to follow than a strict chronic diet, and should avoid weight loss.

PMID- 29061800
TI  - Cytotoxic Effect of Nano-SiO2 in Human Breast Cancer Cells via Modulation of EGFR
      Signaling Cascades.
AB  - BACKGROUND/AIM: Silica nanoparticles (nano-SiO2) are widely used in many
      industrial areas and there is much controversy surrounding cytotoxic effects of
      such nanoparticles. In order to determine the toxicity and possible molecular
      mechanisms involved, we conducted several tests with two breast cancer cell
      lines, MDA-MB-231 and Hs578T. MATERIALS AND METHODS: After exposure to nano-SiO2,
      growth, apoptosis, motility of breast cancer cells were monitored. In addition,
      modulation of signal transduction induced by nano-SiO2 was detected through
      western blot analysis. RESULTS: Treatment of nano-SiO2 repressed the growth of
      breast cancer cell lines. It also increased apoptosis and reduced cell motility.
      Moreover, exposure to nano-SiO2 significantly disturbed the dimerization of
      epidermal growth factor receptor (EGFR), followed by down-regulation of its
      downstream cellular sarcoma kinase (c-SRC) and signal transducer and activator of
      transcription 3 (STAT3) signaling cascades. CONCLUSION: Nano-SiO2 has a cytotoxic
      effect on MDA-MB-231 and Hs578T breast cancer cells via modulation of EGFR
      signaling cascades.

PMID- 29061802
TI  - MYD88 Inhibitor ST2825 Suppresses the Growth of Lymphoma and Leukaemia Cells.
AB  - BACKGROUND/AIM: Myeloid differentiation primary response gene 88 (MYD88), which
      activates the nuclear factor kappa B (NF-kappaB) pathway, is important for the
      growth of lymphoma and leukaemia cells. In this study, we investigated the
      effects of ST2825, a synthetic peptidomimetic compound which inhibits MYD88
      homodimerization, on their growth. MATERIALS AND METHODS: Seven lymphoma and
      leukaemia cell lines including TMD8, a B-cell lymphoma line with MYD88-activating
      mutation, were treated with ST2825 and analysed for cell proliferation and
      expression of NF-kappaB signalling-related molecules. RESULTS: ST2825 suppressed
      the growth of all cell lines by inducing apoptosis and down-regulating
      phosphorylation of NF-kappaB pathway components inhibitor of nuclear factor kappa
      B kinase (IkappaB) and reticuloendotheliosis oncogene A (RelA), as well as of
      MYD88 activator Bruton tyrosine kinase (BTK), suggesting that MYD88 may affect
      BTK activity. ST2825 effects were specific as MYD88-targeting siRNA also
      suppressed phosphorylation of NF-kappaB signalling proteins and BTK in TMD8
      cells. CONCLUSION: ST2825 may be a novel drug targeting not only B-lymphoid
      malignancies with MYD88 mutations, but also lymphoma and leukaemia with wild-type
      MYD88.

PMID- 29061803
TI  - Enoxacin with UVA Irradiation Induces Apoptosis in the AsPC1 Human Pancreatic
      Cancer Cell Line Through ROS Generation.
AB  - Pancreatic cancer is one of the deadliest human cancers. In the current study, we
      investigated the possibility of a new treatment strategy using a combination of
      the new fluoroquinolone, enoxacin, and mild ultraviolet A (UVA) irradiation.
      Enoxacin with UVA irradiation increased the number of annexin V-positive
      (apoptotic) pancreatic cancer cells in time- and concentration-dependent manners,
      whereas alone neither had these effects. In addition, enoxacin with UVA
      irradiation induced cleavage of poly (ADP-ribose) polymerase in AsPC1 human
      pancreatic cancer cells. Moreover, the singlet oxygen scavengers, histidine and
      sodium azide, and the hydroxyl radical scavenger, mannitol, significantly
      suppressed apoptosis induced by enoxacin and UVA irradiation, respectively. These
      results suggest that UVA irradiation activates enoxacin, after which activated
      enoxacin induces apoptosis of AsPC1 cells through generation of reactive oxygen
      species. Therefore, the combination of enoxacin with mild UVA irradiation may be
      a useful method for treating pancreatic cancer.

PMID- 29061804
TI  - 1alpha,25(OH)2D3 Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Metastasis
      After VEGF-A Stimulation.
AB  - AIMS: Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an
      advanced stage. Most patients with PanNETs die of metastasis. Vascular
      endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and
      tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2alpha-(3
      hydroxypropyl)-1alpha,25(OH)2D3], a 1alpha,25-dihydroxy-vitamin D3
      (1alpha,25(OH)2D3) analog, on PanNET cell metastasis after VEGF-A stimulation.
      MATERIALS AND METHODS: Migration and invasion assays, western blot, and
      immunofluorescent staining were applied in this study. RESULTS: VEGF-A increased
      PanNET cell migration and invasion, which was attenuated by 1alpha,25(OH)2D3 and
      MART-10. VEGF-A treatment stimulated epithelial-mesenchymal transition (EMT) of
      PanNET cells. During this process, expression of snail family transcriptional
      repressor 1 and 2, and fibronectin was up-regulated. 1alpha,25(OH)2D3 and MART-10
      counteracted VEGF-A-induced EMT. In addition, expression of neuropilin 1, a key
      protein in VEGF-A signaling, was down-regulated by 1alpha,25(OH)2D3 and MART-10.
      Furthermore, synthesis of F-actin was increased by VEGF-A and reduced by
      1alpha,25(OH)2D3 and MART-10. CONCLUSION: Our data indicate that MART-10 could be
      deemed a promising drug for PanNET treatment.

PMID- 29061805
TI  - Phenethyl Isothiocyanate (PEITC) and Benzyl Isothiocyanate (BITC) Inhibit Human
      Melanoma A375.S2 Cell Migration and Invasion by Affecting MAPK Signaling Pathway
      In Vitro.
AB  - BACKGROUND/AIM: Numerous evidence has shown that PEITC and BITC inhibit cancer
      cell migration and invasion. In this study, we investigated the anti-metastatic
      mechanisms of PEITC and BITC in human melanoma cancer A375.S2 cells in vitro.
      MATERIALS AND METHODS: We used a cell viability assay, an in-vitro scratch wound
      healing assay, a transwell assay for cell migration and invasion, a gelatin
      zymography assay, western blotting and EMSA to examine the anti-metastatic
      mechanisms of PEITC and BITC in A375.S2 cells. RESULTS: Sublethal concentrations
      of PEITC (0, 1, 2 and 2.5 MUM) and BITC (0, 0.5, 1 and 2 MUM) inhibited mobility,
      migration and invasion of A375.S2 cells that were assayed by wound healing and
      Transwell filter. PEITC and BITC inhibited MMP-2 activity in A375.S2 cells, as
      assessed by gelatin zymography assay. Results from western blotting indicated
      that PEITC (2.5 MUM) and BITC (2 MUM) decreased the levels of p-p38 following 24
      and 48 h treatment. PEITC (1-2.5 MUM) reduced the levels of p-JNK1/2 proteins
      following 48-h treatment but BITC increased p-JNK1/2 levels following 24-h
      treatment. PEITC (2.5 MUM) reduced the levels of p-ERK1/2 proteins following 48-h
      treatment but BITC (0.5-2 MUM) increased p-ERK1/2 levels following 24- and 48-h
      treatment. PEITC and BITC affect cell migration and invasion of A375.S2 cells via
      MAPK pathway. PEITC and BITC inhibited MMP-2 activity. PEITC increased NF-kappaB
      expression but BITC decreased NF-kappaB expression in the nucleus. Furthermore,
      NF-kappaB p65 binding to DNA was decreased following 2.5 MUM PEITC treatment, but
      increased following treatment with 1-2 MUM. However, 0.5-2 MUM BITC treatment
      decreased the binding of NF-kappaB to DNA in A375.S2 cells, as assessed by
      electrophoretic mobility shift (EMSA) assay. CONCLUSION: Based on these
      observations, we suggest that PEITC and BITC can be used as anti-metastastic
      agents of human melanoma cells in the future.

PMID- 29061806
TI  - Mifepristone Has Limited Activity to Enhance the In Vivo Efficacy of Docetaxel
      and Enzalutamide Against Bone Metastatic and Castration-Resistant Prostate
      Cancer.
AB  - BACKGROUND: Mifepristone has gained great interest in its potential as a novel
      agent against human cancers, including prostate cancer (PCa). However, recent
      clinical trials using mifepristone in PCa and other cancers have been
      disappointing. We evaluated the in vitro and in vivo activities of mifepristone,
      in combination with docetaxel and enzalutamide, against bone metastatic
      castration-resistant PCa. MATERIALS AND METHODS: The effects of mifepristone,
      alone or in combination with docetaxel or enzalutamide, on PCa cell viability, in
      vitro, were determined by the colorimetric assay. Intratibial model of C4-2-Luc
      tumors in athymic nude mice was used to evaluate the in vivo efficacy of
      mifepristone alone or in combination with docetaxel or enzalutamide. Tumor growth
      in mouse bone was assessed by serum prostate-specific antigen (PSA) levels and
      radiography. RESULTS: Although mifepristone exhibits a certain degree of
      synergism with docetaxel or enzalutamide in cell culture, statistical analyses
      showed that combination regimens fail to demonstrate effectiveness in suppressing
      the skeletal growth of PCa and enhancing the in vivo efficacy of docetaxel or
      enzalutamide in athymic nude mice (p>0.05). CONCLUSION: These results provide the
      first pre-clinical evidence suggesting that mifepristone may not effectively
      inhibit bone metastatic PCa, either as a single agent or combined with standard
      chemotherapy and androgen-deprivation therapy. This report may raise concerns
      over the clinical use of mifepristone in the management of advanced PCa.

PMID- 29061807
TI  - Molecular Interactions of Carcinogenic Aromatic Amines, 4-Aminobiphenyl and 4,4'
      Diaminobiphenyl, with Lactoperoxidase - Insight to Breast Cancer.
AB  - BACKGROUND/AIM: Lactoperoxidase (LPO) is an antimicrobial protein present in
      milk, saliva, gastric secretions, tears and upper respiratory tract secretions.
      LPO constitutes an important enzyme of the human immune defense system. However,
      LPO has also been suggested to be involved in breast cancer etiology through
      production of reactive free radicals and activation of carcinogenic aromatic
      compounds. Aromatic compounds are generally highly lipophilic and thus accumulate
      in highly fatty breast tissues. The aromatic compounds 4-aminobiphenyl (ABP) and
      4,4'-diaminobiphenyl (BZ) are known to have carcinogenic properties. LPO
      catalyzes their oxidation and converts them into reactive products which bind to
      DNA and form adducts. These DNA adducts subsequently lead to breast cancer.
      MATERIALS AND METHODS: The crystal structure of LPO was obtained from Protein
      Data Bank. Structures of ABP and BZ were retrieved from PubChem database. Induced
      Fit Docking was performed using glide module from Schrodinger. RESULTS: The
      present study reports the structural binding of ABP and BZ with LPO using in
      silico approaches. The amino acid residues of LPO involved in the binding with
      the two aromatic ligands were characterized and binding energy values were
      calculated. CONCLUSION: Both ABP and BZ were placed in the substrate binding site
      present in the distal heme cavity of LPO with good affinity. The binding mode
      mimicked that of the natural substrate since these compounds did not disturb the
      water molecule that plays an important role in the oxidation reaction. Thus, the
      water molecule is potentially available for facilitating the subsequent
      activation of the aromatic amines to reactive species which may form DNA adducts
      leading to breast cancer.

PMID- 29061808
TI  - The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human
      Endometrial Adenocarcinoma Cell Line HEC-1-A.
AB  - AIM: We investigated the effect of photodynamic therapy (PDT) using radachlorin
      on invasion, vascular formation and apoptosis by targeting epidermal growth
      factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2)
      signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line. MATERIALS
      AND METHODS: To investigate the apoptotic pathway, we performed the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western
      blot analysis. We also evaluated the effects of PDT on tubular capillary
      formation in and invasion by HEC-1-A cells with a tube formation assay, invasion
      assay, prostaglandin E2 (PGE2) assay, and western blot analysis. RESULTS: PDT had
      anticancer effects on HEC-1-A through activation of the intrinsic pathway of
      apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also
      inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF
      pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog
      gene family/ member A (RhoA) and PGE2. These results are indicative of the
      specificity of radachlorin-mediated PDT to VEGF. CONCLUSION: The major advantage
      of radachlorin-mediated PDT is its selectivity for cancer tissue while
      maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated
      PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an
      especially useful modality for preserving fertility.

PMID- 29061809
TI  - Apoptosis-inducing Effect of Hydroquinone 5-O-Cinnamoyl Ester Analog of
      Renieramycin M on Non-small Cell Lung Cancer Cells.
AB  - BACKGROUND: A newly-synthesized derivative of renieramycin M (RM), an anticancer
      lead compound isolated from the blue sponge Xestospongia sp., hydroquinone 5-O
      cinnamoyl ester (CIN-RM), was investigated here for its activity against non
      small cell lung cancer cells. MATERIALS AND METHODS: Cytotoxicity effects of CIN
      RM and RM on H292 lung cancer cells were determined by the MTT assay. We also
      investigated the mechanism of CIN-RM-mediated apoptosis and mechanism of action
      of this compound by western blotting. RESULTS: CIN-RM showed more potent
      cytotoxicity than its parental compound (RM) against H292 lung cancer cells. At
      concentrations of 15-60 MUM, CIN-RM significantly induced apoptosis by increasing
      expression of apoptosis-inducing factor (AIF) and activation of caspase-3 and -9.
      For up-stream mechanism, CIN-RM mediated apoptosis through a p53-dependent
      mechanism, that consequently down-regulated anti-apoptotic B-cell lymphoma 2
      (BCL2), while increasing the level of pro-apoptotic BCL2-associated X (BAX). In
      addition, phosphorylation of pro-survival protein AKT was found to be
      dramatically reduced. CONCLUSION: This study revealed the potential of CIN-RM for
      apoptosis induction and in the development of a novel anticancer agent.

PMID- 29061810
TI  - Anticancer Effects of Colchicine on Hypopharyngeal Cancer.
AB  - Colchicine is an alkaloid widely used for the treatment of inflammatory diseases,
      such as gout. It suppresses cell division by inhibiting mitosis. We investigated
      the anticancer effects of colchicine on human hypopharyngeal cancer cells and the
      mechanisms underlying its anticancer effects. XTT cell proliferation assay showed
      that colchicine inhibited the growth and proliferation of human hypopharyngeal
      cancer cells (FaDu and SNU1041) in a dose- and time-dependent manner. Colchicine
      also inhibited the migration, invasion, and adhesion of hypopharyngeal cancer
      cells in a dose-dependent manner. The levels of mRNA expression and activity of
      matrix metalloproteinase-9 (MMP9) and urokinase-type plasminogen activator (uPA)
      decreased after treatment with colchicine. Further investigation revealed that
      colchicine inhibited the phosphorylation of the FAK/SRC complex and paxillin.
      Tumor volume ratios in colchicine-treated mice (0.1 mg/kg, every 2 days for 14
      days) increased less than in control mice. To our knowledge, this is the first
      report showing that colchicine can suppress cell invasion, migration, and
      adhesion through reduced expression of MMP9, the uPA system, and the FAK/SRC
      complex. Colchicine has the potential to prevent disease progression in
      hypopharyngeal cancer and may have application as an adjunctive treatment.

PMID- 29061811
TI  - Batatasin III Inhibits Migration of Human Lung Cancer Cells by Suppressing
      Epithelial to Mesenchymal Transition and FAK-AKT Signals.
AB  - BACKGROUND/AIM: Lung cancer is the leading cause of cancer-related deaths
      worldwide. Compound Batatasin III isolated from Dendrobium draconis Rchb.f. was
      tested for the possible anti-cancer activities including anti-proliferative, anti
      migration and invasion in human non-small lung cancer H460 cells. MATERIALS AND
      METHODS: The effect of Batatasin III on viability and proliferation of H460 cells
      was investigated by the 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyl
      tetrazoliumbromide (MTT) assay. Migration and invasion assays were performed.
      Filopodia formation was determined by phalloidin-rhodamine staining. The hallmark
      signaling proteins in regulation of epithelial to mesenchymal transition (EMT),
      proliferation, and migration were determined by western blot analysis. RESULTS:
      Batatasin III at concentrations lower than 100 MUM has no cytotoxic effects. The
      compound at 25-100 MUM exhibited anti-proliferative activity at 48 h after
      treatment. Regarding cell motility, Batatasin III decreased migration and
      invasion of cells. Filopodia were found to be significantly reduced in Batatasin
      III treated cells. These effects correlated with the results from western blot
      analysis showing that the phosphorylation of focal adhesion kinase on Try397 (p
      FAK (Try397)), the active protein kinase B (AKT), and cell division cycle 42
      (CDC42) were significantly reduced. Besides, Batatasin III significantly
      suppressed EMT indicated by the decrease of N-cadherin and Vimentin, and up
      regulation of E-cadherin. CONCLUSION: Batatasin III has anti-cancer activities;
      inhibits cancer migration and invasion by suppressing EMT. Our findings establish
      Batatasin III as a potential compound for further studies aimed at finding a
      better, more effective treatment approach for lung cancer.

PMID- 29061813
TI  - Effect of Agmatine Sulfate on Modulation of Matrix Metalloproteinases via
      PI3K/Akt-1 in HT1080 Cells.
AB  - BACKGROUND/AIM: The purpose of this study was to investigate the mechanism by
      which agmatine sulfate induces an anti-metastatic effect in human HT1080
      fibrosarcoma cells, by affecting matrix metalloproteinases (MMPs). MATERIALS AND
      METHODS: For the experiments, we used a non-toxic concentration of agmatine,
      below 512 MUM, that was determined using an MTT assay. The effect of agmatine
      sulfate on metastasis was gelatin zymography, western blot, immunofluorescence
      staining and cell invasion assay. RESULTS: Agmatine sulfate inhibited MMP-2
      activity stimulated by phenazine methosulfate (PMS). Furthermore, the expression
      level of MMP-2 stimulated by PMS, was decreased, but the expression level of TIMP
      1 was increased in the presence of agmatine sulfate. Moreover, it was observed
      that the expression levels of ERK and p38 were increased, but those of PI3K and
      Akt-1 associated with the modulation of MMP-2 were decreased in this study.
      Furthermore, agmatine sulfate decreased the invasion level of human fibrosarcoma
      cells stimulated by VEGF. CONCLUSION: These results suggest that agmatine sulfate
      could inhibit metastasis through inhibition of MMP-2 via the PI3K/Akt-1 signaling
      pathway.

PMID- 29061814
TI  - Cycloartobiloxanthone Inhibits Migration and Invasion of Lung Cancer Cells.
AB  - BACKGROUND/AIM: Metastasis in lung cancer is a major cause of high mortality.
      Metastasis depends on the potential of cancer cells to migrate and invade. Here
      we demonstrated the anti-migration and invasion activities of the compound
      cycloartobiloxanthone from Artocarpus gomezianus Wall. ex Trec. (Moraceae).
      MATERIALS AND METHODS: The effect of the compound on viability of human lung
      cancer H460 cells was investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5diphenyl
      tetrazoliumbromide (MTT) assay. Migration and invasion assays were performed.
      Filopodia formation was determined by phalloidin-rhodamine staining. The hallmark
      signaling proteins in regulation of epithelial to mesenchymal transition (EMT),
      migration, and integrin alpha5, alphaV, beta1 and beta3 were determined by
      western blot analysis. RESULTS: Cycloartobiloxanthone at concentrations lower
      than 10 MUM has no cytotoxic effects. Regarding cell motility,
      cycloartobiloxanthone at 5-10 MUM and 1-10 MUM exhibited anti-migration and anti
      invasion activities, respectively. Filopodia were found to be significantly
      reduced in cycloartobiloxanthone-treated cells. These effects correlated with the
      results from western blot analysis showing that the phosphorylation of focal
      adhesion kinase on Try397 (p-FAK (Try397)), and cell division cycle 42 (CDC42)
      were significantly reduced. Cycloartobiloxanthone significantly suppressed
      migratory integrins including integrin alpha5, alphaV, and beta3, while had no
      significant effect on integrin beta1. Besides, the compound suppressed epithelial
      to mesenchymal transition in lung cancer H460 cells indicated by the change in
      cell morphology form fibroblast-like to epithelial morphology with up-regulation
      of E-cadherin. CONCLUSION: Cycloartobiloxanthone possesses anti-migration and
      anti-invasion properties by suppressing several migratory-regulated mechanisms
      including suppressing migratory FAK and CDC42 signal, reduced filopodia of
      migrating cells, decreasing integrin alpha5, alphav and beta3, and inhibiting
      EMT. Our findings demonstrated the potentials of cycloartobiloxanthone for
      further studies and developments.

PMID- 29061812
TI  - Tumor Suppression Efficacy of Heat Shock Protein 90 Inhibitor 17AAG in a
      Liposarcoma Mouse Model.
AB  - BACKGROUND/AIM: Heat shock protein 90 (HSP90) inhibitors have recently been
      tested as anticancer drugs in a variety of carcinomas. Yet, there exist only few
      reports about HSP90 inhibitor and its thepeutic effect on liposarcoma. The
      therapeutic effects of HSP90 inhibitors have been mainly observed in oncogenic
      and tumor angiogenic signaling cascades by observing tumor growth. MATERIALS AND
      METHODS: We used the the LPS 246 liposarcoma cell line and GS-076 PDC (patient
      derived cell lines). On these, we performed cell viability assays and migration
      assays under treatment with the HSP90 inhibitor, 17AAG. For analyzing
      angiogenesis factor, we used quantitative polymerase chain reaction (qPCR) after
      treating cells with the 17AAG inhibitor. Regarding in vivo assay, we made the
      tumor model in immune-deficient mouse and compared the tumor size of drug-treated
      group at each time point with controls. For sequestering analysis of angiogenesis
      factor in vivo, we performed immuno-fluorescence (IF) staining on tumor tissue.
      RESULTS: Through cell viability, migration assay and qPCR about angiogenesis
      factor, we demonstrated the anti-oncogenic and anti-angiogenic effects of an
      HSP90 inhibitor on a liposarcoma cell line and a patient-derived primary cell
      model (PDC). Also, the HSP90 inhibitor 17AAG effectively inhibited the activity
      of protein kinase B (AKT) and blocked extracellular signal-regulated kinase (ERK)
      activity. Hence, 17AAG effectively disrupted the oncogenic signaling cascade and
      substantially inhibited tumor growth in vitro. In an LPS 863 cell xenograft mouse
      model treated with 17AAG, we observed that tumor size was decreasing, as well as
      down-regulation of the expression levels of vascular endothelial growth factor
      receptor 2 (VEGFR2), CD31 and signal transducer and activator of transcription-3
      (STAT3). CONCLUSION: 17AAG reduced the activity of AKT, ERK, VEGF and STAT3 in
      oncogenic and angiogenic pathways in liposarcoma PDC models derived from
      patients' tissues and cancer cell lines.

PMID- 29061815
TI  - Orlistat Reduces Proliferation and Enhances Apoptosis in Human Pancreatic Cancer
      Cells (PANC-1).
AB  - BACKGROUND/AIM: Pancreatic cancer is a disease with very poor prognosis, and none
      of currently available pharmacotherapies have proven to be efficient in this
      indication. The aim of this study was to analyze the expression of fatty acid
      synthase (FASN) gene as a potential therapeutic target in proliferating human
      pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as
      an anti-obesity drug, inhibits PANC-1 proliferation. MATERIALS AND METHODS: The
      effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis
      was studied in PANC-1 cell culture. RESULTS: Expression of FASN increased during
      proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant
      reduction of PANC-1 proliferation and enhanced apoptosis of these cells.
      CONCLUSION: This study showed, to our knowledge for the first time, that orlistat
      exhibits significant antitumor activity against PANC-1 cells. This implies that
      orlistat analogs with good oral bioavailability may find application in
      pharmacotherapy of pancreatic cancer.

PMID- 29061816
TI  - Relationship Between Structure and Antiproliferative Activity of Novel 5-amino-4
      cyanopyrazole-1-formaldehydehydrazono Derivatives on HL-60RG Human Leukemia
      Cells.
AB  - BACKGROUND: Pyrazole derivatives have been reported to have potent antimicrobial
      and anticancer activity. We recently synthesized and determined the effects of
      analogs, benzamidoxime derivatives, on mammalian cells and discovered that
      benzamidoximes had an antiproliferative effect. Here we synthesized and
      determined the anticancer effects of hydrazonopyrazole derivatives on a mammalian
      cancer cell line. MATERIALS AND METHODS: We synthesized 12 hydrazonopyrazole
      derivatives with several constant alkyl chain length or branched chains at the
      side chain to investigate their anticancer cell activity, using the human
      myelogenous leukemia cell line HL-60RG. RESULTS: Among all hydrazonopyrazole
      derivatives we synthesized, the hydrazonopyrazole derivative with a branched
      chain at the side chain rather than a constant alkyl chain significantly
      inhibited cell viability. The strongest hydrazonopyrazole derivative, 5-amino-4
      cyanopyrazole-1-formaldehydehydrazono-3'-pentanal, tended to damage cells dose
      dependently. This cell growth attenuation was a result of apoptosis, activating
      caspase-3 and fragmented DNA. CONCLUSION: Hydrazonopyrazole derivatives induced
      apoptosis of HL-60RG leukemia cells.

PMID- 29061817
TI  - Synergistic Inhibition of Human Carcinoma Cell Growth via Co-Delivery of p53
      Plasmid DNA and bcl-2 Antisense Oligodeoxyribonucleotide by Cholic Acid-modified
      Polyethylenimine.
AB  - BACKGROUND/AIM: This study investigated the co-delivery of plasmid DNA and
      antisense oligodeoxyribonucleotide (AS ODN) into carcinoma cells by cholic acid
      modified polyethylenimine (PEI-CA). MATERIALS AND METHODS: PEI-CA/plasmid DNA and
      AS ODN complexes were formulated and evaluated for delivery of plasmid DNA and AS
      ODN in HeLa cells. The efficiency of co-delivery of plasmid DNA and AS ODN was
      evaluated by cell growth inhibition using p53 and bcl-2 AS ODN. RESULTS: AS ODN
      intracellular delivery and green fluorescent protein expression upon cellular
      transfection were greater than in cells treated with uncomplexed nucleic acids.
      Treatment of the cells with PEI-CA/p53 plasmid DNA and bcl-2 AS ODN complexes
      resulted in cell growth inhibition that was greater than that of either PEI
      CA/p53 plasmid DNA complexes or PEI-CA/bcl-2 AS ODN complexes alone. CONCLUSION:
      The co-delivery of p53 plasmid DNA and bcl-2 AS ODN in PEI-CA complexes enhanced
      therapeutic activities of both p53 plasmid DNA and bcl-2 AS ODN.

PMID- 29061818
TI  - The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines.
AB  - BACKGROUND: Studies have revealed that cancer might be treated with cannabinoids
      since they can influence cancer cell survival. These findings suggest an
      alternative treatment option to chemo- and radiotherapy, that are associated with
      numerous adverse side-effects for the patients. MATERIALS AND METHODS: Viability
      staining was conducted on lung cancer, testicular cancer and neuroblastoma cells
      treated with different concentrations of the synthetic cannabinoid WIN 55,212-2
      and the percentage of dead cells was compared. Activity of apoptosis-related
      enzymes was investigated by the presence of DNA ladder in gel electrophoresis.
      RESULTS: Treatment with different WIN 55,212-2 concentrations led to a
      significant dose-dependent reduction of cell viability. A DNA ladder was observed
      after WIN 55,212-2 treatment of testicular cancer and lung cancer cells.
      CONCLUSION: The application of WIN 55,212-2 was found to trigger cell death in
      the investigated cell lines. The decline in lung cancer and testicular cancer
      cell viability seems to have been caused by apoptosis. These findings may
      contribute to development of alternative cancer therapy strategies.

PMID- 29061819
TI  - Effect of Tumor Microenvironment on Selective Uptake of Boric Acid in HepG2 Human
      Hepatoma Cells.
AB  - BACKGROUND: Feasibility and efficacy of boric acid (BA)-mediated boron neutron
      capture therapy (BNCT) was first demonstrated by eliminating hepatocellular
      carcinoma (HCC) in a rat model. Furthermore, selective uptake of BA by liver
      tumor cells was shown in a rabbit model. To gain further insight, this study
      aimed to investigate the mechanisms of transportation and selective uptake of BA
      in HepG2 liver tumor cells. MATERIALS AND METHODS: Transportation of BA in HepG2
      cells was analyzed by time-course assays and by analyzing the rate of diffusion
      versus the concentration of BA. The effect of different tumor conditions on BA
      uptake was studied by treating HepG2 cells with 25 MUg 10B/ml BA under different
      concentrations of glucose, at different pH and in the presence of water-soluble
      cholesterol. RESULTS: HepG2 cells mainly uptake BA by simple diffusion. Cell
      membrane permeability may also contribute to tumor-specific uptake of BA.
      CONCLUSION: The selective uptake of BA was achieved primarily by diffusion, while
      other factors, such as low pH and increased membrane fluidity, which are
      hallmarks of HCC, might further enhance BA uptake.

PMID- 29061820
TI  - Comparison of In Vitro Antileukemic Activity of 4-Hydroperoxyifosfamide and 4
      Hydroperoxycyclophosphamide.
AB  - BACKGROUND/AIM: The oxazaphosphorines, ifosfamide and cyclophosphamide, represent
      a class of alkylating agents. The aim of the present in vitro study was to
      compare antileukemic activity of 4-hydroperoxyifosfamide (4-OOH-IF) and 4
      hydroperoxycyclophosphamide (4-OOH-CP). MATERIALS AND METHODS: The experiments
      were performed on MOLT-4 and ML-1 cells. The research was conducted using flow
      cytometry fluorescein diacetate/propidium iodide (PI), fluorescein-conjugated
      annexin V/PI, CaspGLOW Red Active Caspase-8 and -9, CellEventTM Caspase-3/7 Green
      assays, and tetramethylrhodamine ethyl ester test. RESULTS: 4-OOH-IF and 4-OOH-CP
      distinctly reduced cell viability and triggered apoptosis and necrosis, causing
      changes in intracellular esterase activity, plasma membrane structure and
      integrity, caspase activation, and mitochondrial membrane potential. The
      oxazaphosphorines were responsible for the different antileukemic activities. 4
      Hydroperoxyifosfamide appeared to be less cytotoxic against the leukemia cells
      than 4-hydroperoxycyclophosphamide. MOLT-4 cells were more sensitive to the
      action of the oxazaphosphorines than ML-1 cells. CONCLUSION: The findings provide
      a new insight on the mechanisms of cytotoxic action of 4-OOH-IF and 4-OOH-CP on
      the human acute lymphoblastic and myeloblastic leukemia cells.

PMID- 29061821
TI  - In Vitro Antileukemic Activity of Formamidine Epidoxorubicin Analogs.
AB  - BACKGROUND/AIM: Epidoxorubicin is an anthracycline agent. The present study was
      undertaken to compare the antileukemic potential of epidoxorubicin and its two
      formamidine analogs containing either a morpholine moiety (EPIFmor) or a
      hexamethyleneimine moiety (EPIFhex) in the amidine group. MATERIALS AND METHODS:
      The experiments were performed in vitro on MOLT-4 cells using spectrophotometry,
      Coulter electrical impedance, flow cytometry, and light microscopy methods.
      RESULTS: The leukemia cell responses to the action of the anthracyclines were
      manifested in their different viability, count and volume, degree of apoptosis
      and necrosis, activity of caspases -8, -9, and -3/7, mitochondrial membrane
      potential, and in the cell-cycle distribution. In general, epidoxorubicin
      appeared to be the most active, and EPIFmor was more active than EPIFhex against
      MOLT-4 cells. CONCLUSION: The structural modifications of epidoxorubicin in the
      amidine group were responsible for the varied action of its formamidine analogs
      on human acute lymphoblastic leukemia cells.

PMID- 29061822
TI  - In Vitro Effects of Bromoalkyl Phenytoin Derivatives on Regulated Death, Cell
      Cycle and Ultrastructure of Leukemia Cells.
AB  - BACKGROUND/AIM: To search for new antileukemic agents, the chemical structure of
      phenytoin was modified. A possible cytotoxic activity of three bromoalkyl
      phenytoin analogs, methyl 2-(1-(3-bromopropyl)-2,4-dioxo-5,5-diphenylimidazolidin
      3-yl) propanoate (PH2), 1-(3-bromopropyl)-3-methyl-5,5-diphenylimidazolidine-2,4
      dione (PH3) and 1-(4-bromobutyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione
      (PH4) on regulated cell death, the cell cycle and cell ultrastructure was
      assessed. MATERIALS AND METHODS: The experiments were performed in vitro on HL-60
      and U937 cells, using flow cytometry and electron microscopy methods. RESULTS:
      Application of PH2, PH3, and PH4 resulted in cell surface exposure of
      phosphatidylserine and plasma membrane impairment, caspase-8, -9, and -3/7
      activation, dissipation of mitochondrial membrane potential, DNA breakage, cell
      cycle disturbance and cell ultrastructural changes. In general, PH3 appeared to
      be the most active against the leukemia cells, and all bromoalkyl hydantoins, PH2
      PH4, were more active in HL-60 cells than in U937 cells. CONCLUSION: The
      antileukemic activity of the bromoalkyl phenytoin analogs depended on the
      combination of N-hydantoin substituents and the human cell line used.

PMID- 29061823
TI  - Synthesis of 2-Substituted Benzothiazole Derivatives and Their In Vitro
      Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells.
AB  - Pancreatic cancer is one of the deadliest malignancies characterized by strong
      resistance to almost all chemotherapeutic agents and radiotherapy. In this study,
      we aimed to investigate the anticancer effect, enzymatic antioxidant activity
      [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and total antioxidant
      capacity (TAC) of synthesized benzothiazole compounds against adenocarcinoma
      cancer cells (PANC-1). 2-((1S,2S)-2-((E)-4-nitrostyryl)cyclopent-3-en-1
      yl)benzo[d]thiazole and 2-((1S,2S)-2-((E)-4-fluorostyryl) cyclopent-3-en-1
      yl)benzo[d]thiazole containing 2-substituted benzothiazole group were synthesized
      in two steps. PANC-1 cells were treated with different concentrations of
      benzothiazole compounds (5, 25, 50. 75 and 100 MUM) for 48 h and their
      cytotoxicity effects were determined by the MTT assay. To determine whether these
      compounds induced apoptosis, PANC-1 cells were treated with increasing
      concentrations of the synthetic products. Our study showed that the synthesized
      compounds have antiproliferative effects against PANC-1 cells and reduced cell
      viability. These compounds induced apoptosis of pancreatic cancer cells and at
      the same time reduced the activity of SOD and GPx and reduced TAC. On the basis
      of these findings, these synthesized benzothiazole compounds may be considered as
      a potential therapeutic drug against human PANC-1 cancer cells.

PMID- 29061824
TI  - Pipoxolan Exhibits Antitumor Activity Toward Oral Squamous Cell Carcinoma Through
      Reactive Oxygen Species-mediated Apoptosis.
AB  - Pipoxolan is frequently prescribed as a smooth muscle relaxant. Pipoxolan has
      also been shown to have anticancer activity. Our study investigated whether
      pipoxolan induced apoptosis in oral squamous cell carcinoma (OSCC). Cell
      cytotoxicity was evaluated by the MTT assay. Cell apoptosis and cell-cycle
      distribution were measured by annexin V/propidium iodide (PI) double staining and
      flow cytometry, respectively. Apoptotic-related proteins were assessed by western
      blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane
      potential (MMP) were measured with fluorescent probes. Following exposure of
      TW206 OSCC cells to pipoxolan, a time-dependently decrease in MMP and an increase
      in ROS were observed. However, these effects were significantly abrogated by the
      free radical scavenger N-acetyl-L-cysteine. Since high levels of ROS were
      produced early in the treatment, intracellular ROS seemed to play a key role in
      pipoxolan-induced apoptosis. In HSC-3 OSCC cells, our results demonstrated that
      pipoxolan treatment caused a time-dependent increase of protein expression of
      active caspase-3 and -9, cytosolic cytochrome c, cleavage of poly (ADP-ribose)
      polymerase, and B-cell lymphoma 2 (BCL2)-like protein 4 (BAX). However,
      expression of BCL2 itself was reduced. Clearly, such an increase in BAX/BCL2
      ratio would be associated with apoptosis. In addition, pipoxolan markedly
      suppressed the protein expression of phosphatidylinositol-4,5-bisphosphate 3
      kinase (PI3K) and phosphorylation of protein kinase B (AKT). These data suggest
      that pipoxolan acts against HSC-3 in vitro via intrinsic apoptotic signaling
      pathways, and inhibition of PI3K/AKT signaling.

PMID- 29061825
TI  - In Vitro Chemosensitivity Test for Gastric Cancer Specimens Predicts
      Effectiveness of Oxaliplatin and 5-Fluorouracil.
AB  - AIM: Cisplatin plus 5-fluorouracil (5-FU) or S-1 is a standard therapy for
      gastric cancer (GC). However, cisplatin is emetic and potentially nephrotoxic.
      Oxaliplatin may be less toxic, but few basic data are available for this setting.
      Here, we evaluated oxaliplatin for GC, by testing surgical specimens. MATERIALS
      AND METHODS: We evaluated effects of oxaliplatin and 5-FU, alone and in
      combination, on surgical specimens from 11 patients with GC, using collagen gel
      droplet embedded culture drug tests. RESULTS: Oxaliplatin was less efficacious
      than 5-FU, and its synergistic effect was less in tumors highly sensitive to 5-FU
      than in those with low sensitivity. Tumor differentiation and drug sensitivity
      were not correlated. CONCLUSION: Although oxaliplatin monotherapy had little
      effect on GC, we saw a limited synergistic effect of oxaliplatin with 5-FU in 5
      FU-sensitive patients. Collagen gel droplet embedded culture drug tests may
      predict this synergistic effect, and help select candidates for this or other
      regimens.

PMID- 29061826
TI  - Photodynamically-induced Apoptosis Due to Ultraviolet A in the Presence of
      Lomefloxacin in Human Promyelocytic Leukemia Cells.
AB  - Lomefloxacin (LFX) is a widely used fluoroquinolone antimicrobial agent that
      plays an important role in the treatment of human and animal infections; however,
      it has been reported to cause phototoxicity. In this study, we investigated the
      induction of apoptosis due to ultraviolet A (UVA) light in the presence and
      absence of LFX in HL-60 human promyelocytic leukemia cells. HL-60 cells were
      exposed to UVA at an intensity of 1.1 mW/cm2 for 20 min in the presence and
      absence of LFX, and the induction of apoptosis was examined by analyzing cell
      morphology, DNA fragmentation, and caspase-3 activity. Cells treated with 100 MUM
      LFX and UVA clearly showed membrane blebbing and cell shrinkage. The proportion
      of apoptotic cells was significantly higher in cells treated with both UVA and
      LFX than in those treated with UVA or LFX alone. In addition, DNA ladder
      formation and caspase-3 activation were observed in cells treated with both UVA
      and LFX. A significant reduction in the number of UVA-induced apoptotic cells and
      caspase-3 activation was observed when histidine was present, which suggested
      that photodynamically-generated singlet oxygen is an important mediator of
      apoptosis. These results indicate that the combination of UVA and LFX induces
      apoptosis in HL-60 cells.

PMID- 29061827
TI  - Lactoperoxidase, an Antimicrobial Milk Protein, as a Potential Activator of
      Carcinogenic Heterocyclic Amines in Breast Cancer.
AB  - BACKGROUND: Lactoperoxidase (LPO) is an antimicrobial protein secreted from
      mammary, salivary and other mucosal glands. It is an important member of heme
      peroxidase enzymes and the primary peroxidase enzyme present in breast tissues.
      In addition to the antimicrobial properties, LPO has been shown to be associated
      with breast cancer etiology. Heterocyclic amines, an important class of
      environmental and dietary carcinogens, have been increasingly associated with
      breast cancer etiology. Heterocyclic amines undergo activation in breast tissue
      as a result of oxidation by LPO. The current study includes three important
      heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methy-6-phenylimidazo[4,5
      b]-pyridine (PhIP), that have carcinogenic activity. MATERIALS AND METHODS: The
      structural binding characterization of IQ, MeIQx and PhIP with LPO was done using
      in silico approaches. Their binding pattern and interactions with LPO amino acid
      residues were analyzed. RESULTS: The three compounds bound in the distal heme
      cavity of LPO without replacing the important water molecule required for
      oxidation of substrate compounds. PhIP displayed lesser binding affinity for LPO
      in comparison to IQ and MeIQx. The binding mode of heterocyclic amines in distal
      heme cavity of LPO resembled to that of substrate binding pattern. CONCLUSION:
      The three heterocyclic amines are suggested to act as LPO substrate. The
      undisturbed water molecule present in distal heme cavity of the LPO is expected
      to facilitate the oxidation and activation of the three heterocyclic amines.
      These activated compounds may potentially bind with DNA in breast tissues forming
      DNA adducts and may subsequently lead to breast cancer initiation.

PMID- 29061828
TI  - Effect of Adjuvant Gemcitabine Combined with Low-dose 5-Fluorouracil and
      Cisplatin Chemotherapy for Advanced Biliary Carcinoma.
AB  - BACKGROUND/AIM: The aim of this retrospective study was to clarify the
      effectiveness of chemotherapy with gemcitabine combined with low-dose 5
      fluorouracil and cisplatin (GFP) for advanced biliary carcinoma after
      hepatectomy. PATIENTS AND METHODS: Sixty-two patients had biliary carcinoma with
      lymph node metastasis, intrahepatic metastasis or positive surgical margins,
      including intrahepatic cholangiocarcinoma (IHC, n=25), hilar cholangiocarcinoma
      (HC, n=14), and gallbladder cancer (GBC, n=23). Twenty-eight patients (IHC; n=9,
      HC; n=8, GBC; n=11) received adjuvant GFP chemotherapy. RESULTS: We found no
      significant difference in clinicopathological factors in patients treated with or
      without adjuvant GFP chemotherapy. Overall, survival in the adjuvant GFP group
      was significantly better than that in the non-adjuvant GFP group (3-year
      survival: 61.9% vs. 8.8%, p<0.001), as was relapse-free survival. CONCLUSION:
      Adjuvant GFP chemotherapy after hepatectomy may be a promising option for
      improving surgical outcomes in patients with advanced biliary carcinoma.

PMID- 29061829
TI  - Survival Outcomes According to TIMP1 and EGFR Expression in Heavily Treated
      Patients with Advanced Non-small Cell Lung Cancer who Received Biweekly
      Irinotecan Plus Bevacizumab.
AB  - BACKGROUND: Heavily treated patients with non-small cell lung cancer (NSCLC) have
      few treatment options, while irinotecan and bevacizumab have proven synergistic
      action in preclinical studies. PATIENTS AND METHODS: A total of 49 patients with
      heavily treated NSCLC were enrolled from 2011-2014 and treated with irinotecan
      and bevacizumab. Treatment response along with mutational status of epidermal
      growth factor receptor (EGFR), and tissue inhibitor of metalloproteinases-1
      (TIMP1) and EGFR expression were evaluated. Progression-free (PFS) and overall
      (OS) survival were monitored. RESULTS: Median follow-up was 13.2 months. Twenty
      three patients had received three or more prior therapy lines. Overall response
      rate was 32% [95% confidence interval (CI)=22%-39%] and 26% of patients achieved
      stable disease. Median PFS was 4.4 (95% CI=2.8-8.3) months and median OS 18.0
      (95% CI=16.2-30.7) months. Nine patients harboring EGFR mutations had a long
      lasting partial response. A shorter OS was found in patients with a higher TIMP1
      expression (p=0.006). CONCLUSION: Irinotecan combined with bevacizumab had
      favorable antitumor activity in heavily pretreated patients with NSCLC. These
      results suggest this is a reasonable strategy, particularly for patients with low
      TIMP1 expression.

PMID- 29061830
TI  - Vinflunine in the Treatment of Upper Tract Urothelial Carcinoma - Subgroup
      Analysis of an Observational Study.
AB  - BACKGROUND/AIM: Despite an expected prognostic disadvantage for upper tract
      versus lower tract metastatic urothelial carcinomas (UTUC/LTUC), only few studies
      have been conducted to elucidate potential differences in chemotherapy treatment.
      PATIENTS AND METHODS: A post-hoc subgroup analysis of a non-interventional study
      investigating vinflunine after failure of a platinum-based chemotherapy in
      metastatic/locally advanced UC patients was performed. RESULTS: A total of 18 and
      59 out of 77 patients had UTUC and LTUC, respectively. The effectiveness of
      vinflunine treatment was comparable with an overall response rate of 22.2% and
      23.7% respectively and a median progression-free survival of 2.76 months in both
      groups. Median overall survival was 5.0 months in UTUC compared to 8.2 months in
      the LTUC group (p=0.478). The safety profile was in accordance with previous
      vinflunine experiences, with a comparable frequency of adverse events in both
      groups. CONCLUSION: Vinflunine can be applied in the 2nd line for UC regardless
      of the primary tumor localization.

PMID- 29061831
TI  - Bladder Urothelial Carcinoma with Peritoneal Involvement: Benefit of Continuous
      Maintenance Chemotherapy.
AB  - AIM: We investigated bladder urothelial carcinoma with peritoneal involvement.
      PATIENTS AND METHODS: Inclusion criteria were: pathology-confirmed urothelial
      carcinoma; peritoneal spread identified on computed tomographic (CT) scans
      performed initially or after either cystectomy or concomitant chemoradiotherapy
      (CCRT), and absence of visceral metastases; and chemotherapy administered after
      peritoneal spread was diagnosed. RESULTS: Forty-seven cases included initial
      modes of therapy with chemotherapy in 24 patients (51%), cystectomy in 17 (36%),
      and CCRT in six (13%), only given as a result of under-staging. After local
      therapy, these patients received a continuous maintenance chemotherapy regimen of
      5-fluorouracil, leucovorin, cisplatin, and gemcitabine. The overall response rate
      was 85%, and the side-effects were mild and tolerated. The median survival time
      was 28 months. The survival time of cases initially treated only with
      chemotherapy was not statistically different to that of those with local disease.
      CONCLUSION: Bladder urothelial carcinomas with peritoneal involvement can benefit
      from continuous maintenance chemotherapy.

PMID- 29061832
TI  - Neoadjuvant Chemotherapy for Patients with Muscle-invasive Urothelial Bladder
      Cancer Candidates for Curative Surgery: A Prospective Clinical Trial Based on
      Cisplatin Feasibility.
AB  - BACKGROUND: Neoadjuvant chemotherapy demonstrated a survival benefit versus
      cystectomy alone in muscle-invasive urothelial bladder cancer. Despite this
      advantage, preoperative chemotherapy is not widely employed. When patients are
      unfit for cisplatin-based regimen, they are often candidates for immediate
      surgery. In our study, patients with muscle-invasive bladder cancer were treated
      with neoadjuvant chemotherapy. The principal objective was the rate of complete
      pathological response (pCR). Secondary end-points were disease-free survival
      (DFS), overall survival (OS) and toxicity. PATIENTS AND METHODS: Patients (n=72)
      with Eastern Cooperative Oncology Group (ECOG) performance status 0-1, clinical
      stage cT3-4, and/or N+ muscle-invasive bladder cancer were enrolled. The
      chemotherapy regimen was established according to the cisplatin feasibility.
      Thirty patients were treated with cisplatin/gemcitabine (Gem) and 42 with
      carboplatin/Gem. RESULTS: The rate of pCR was 29.2%, 36% with cisplatin-based
      treatment and 23.8% with carboplatin (p=0.3574). DFS and OS were longer in pCR
      patients, while no difference was reported between cisplatin/Gem and
      Carboplatin/Gem groups. CONCLUSION: Our results confirm the prognostic value of
      pCR in neoadjuvant chemotherapy for muscle-invasive bladder cancer. When the
      patients are not fit for cisplatin, a carboplatin/Gem regimen represents a valid
      option because of comparable long-term outcome. When cisplatin is not feasible,
      the exclusion of a preoperative treatment is not justified.

PMID- 29061834
TI  - Serum Concentration of Erlotinib and its Correlation with Outcome and Toxicity in
      Patients with Advanced-stage NSCLC.
AB  - BACKGROUND: Erlotinib is a tyrosine kinase inhibitor targeting epidermal growth
      factor receptor (EGFR); it is used in the treatment of advanced non-small cell
      lung cancer (NSCLC). We focused on the role of serum concentration of erlotinib
      and its association with outcome and toxicity in patients with advanced NSCLC
      harbouring the wild-type EGFR gene or squamous histology. PATIENTS AND METHODS:
      Clinical data of 122 patients were analyzed. Serum samples were collected within
      four weeks after the initiation of treatment. RESULTS: There was no significant
      association of erlotinib concentration with PFS nor OS (p=0.352 and p=0.6393).
      Significant associations of erlotinib concentration with grade of skin rash and
      diarrhoea (p<0.0001 and p<0.0001) were found. Skin rash and diarrhoea were
      significantly associated with PFS (p=0.0338 and p=0.0001) and OS (p=0.0064 and
      p=0.0353). CONCLUSION: Erlotinib concentration was not associated with outcome.
      Erlotinib concentration was associated with occurrence and severity of skin rash
      and diarrhoea; the outcome was associated with erlotinib toxicity.

PMID- 29061833
TI  - Anti-Epidermal Growth Factor Receptor Antibody Readministration in
      Chemorefractory Metastatic Colorectal Cancer.
AB  - BACKGROUND/AIM: Readministration of anti-epidermal growth factor receptor (EGFR)
      antibody for metastatic colorectal cancer (mCRC) after disease progression
      remains to be determined. PATIENTS AND METHODS: Readministration of anti-EGFR
      antibody in mCRC patients previously refractory to anti-EGFR antibody was
      prospectively observed. RESULTS: A total of thirteen patients with a median age
      of 60-years old and an Eastern Cooperative Oncology Group (ECOG) performance
      status 0 or 1, were enrolled. The median number of previous chemotherapies was 3
      (range 2-5). Prior anti-EGFR antibody in combination with cytotoxic drugs was
      administered in 12 patients. Anti-EGFR antibody readministration regimens were
      cetuximab/panitumumab plus capecitabine/S-1 (seven patients), panitumumab plus
      FOLFOX (three patients), cetuximab plus irinotecan (two patients), and
      panitumumab monotherapy (one patient). Seven patients showed stable disease
      following readministration and six patients showed progressive disease. The
      median overall survival (OS) following readministration was 228 days and the
      median PFS was 102 days. Patients with intervals longer than 90 days between anti
      EGFR therapies exhibited more favorable survival than those with intervals
      shorter than 90 days. Switching of anti-EGFR antibody between treatments was
      observed to contribute survival. CONCLUSION: Anti-EGFR antibody readministration
      could show a modest survival benefit in mCRC patients, with the length of therapy
      interval and switching of antibody being important contributory factors.

PMID- 29061836
TI  - Evaluation of Efficacy and Safety of Upfront Weekly Nanoparticle Albumin-bound
      Paclitaxel for HER2-negative Breast Cancer.
AB  - BACKGROUND: Taxanes are among the key drugs for breast cancer treatment. This
      study aimed to evaluate the efficacy of upfront weekly nanoparticle albumin-bound
      paclitaxel (Nab-PTX; 100 mg/m2) for human epidermal growth factor 2 (HER2)
      negative breast cancer. PATIENTS AND METHODS: Patients with stage II to IV breast
      cancer received 12 cycles of weekly 100 mg/m2 Nab-PTX as first-line treatment.
      Preoperative chemotherapy with anthracyclines after Nab-PTX was recommended.
      RESULTS: From 2012 to 2014, we enrolled 66 patients. The overall response rate
      after Nab-PTX was 59.1% [95% confidence interval(CI)=47.2% to 71.0%), 63.6% in
      those with hormone receptor-positive tumors, and 36.4% in those with triple
      negative tumors. The pathological complete response rate at surgery was 15% (95%
      CI=6.1% to 24.4%). Toxicity analysis showed grade 2 peripheral neuropathy in 38
      patients (57.6%), grade 2/3 leukocytopenia in 29 (43.9%) and grade 2/3 liver
      dysfunction in five (7.5%). CONCLUSION: Weekly neoadjuvant Nab-PTX at 100 mg/m2
      led to good response rates (59.1%) and was well tolerated.

PMID- 29061837
TI  - Immediate and Long-term Results of Radiofrequency Ablation for Colorectal Liver
      Metastases.
AB  - BACKGROUND/AIM: Radiofrequency ablation (RFA) of colorectal liver metastases
      (CRLMs) is a method developed in the last 15 years. It provides an acceptable
      control of the malignant process with lower risks compared to surgical resection.
      The aim of the study was to assess immediate and long-term results, including
      recurrence, survival, morbidity/mortality rates after RFA. PATIENTS AND METHODS:
      Sixty-two cases with CRLMs were treated by RFA during open surgery (89 lesions).
      Patients were followed-up for a minimum of 36 months, with assessment of
      recurrences and survival rates at 1, 2 and 3 years, using computed tomography
      (CT) scan, contrast-enhanced ultrasound and tumor markers (carcinoembryonoc
      antigen, carbohydrate antigen-19.9). RESULTS: Local relapses, recurrences in
      other areas and survival rates at 1, 2 and 3 years suggest acceptable values
      comparative with liver resections in the first 2-3 years and demonstrated long
      term limitations, despite the use of adjuvant chemotherapy. Major postoperative
      negative prognostic factors are tumor multicentricity and tumor's dimensions over
      5 cm. CONCLUSION: RFA of CRLMs is a safe procedure with low rates of local
      relapses and recurrences, as well as acceptable survival rates, in the first 24
      36 months post-procedure. It is recommended for patients with no indications for
      liver resection or having major resection risks.

PMID- 29061835
TI  - Clinical Efficacy of Alectinib in Patients with ALK-Rearranged Non-small Cell
      Lung Cancer After Ceritinib Failure.
AB  - Several second-generation inhibitors of anaplastic lymphoma kinase (ALK) have
      demonstrated potent activity in ALK rearrangement-positive non-small cell lung
      cancer (NSCLC). Two of these agents, ceritinib, and alectinib, recently received
      approval for the treatment of ALK-rearranged NSCLC in Japan. The efficacy of
      treatment with a second-generation ALK inhibitor after failure with a different
      second-generation ALK inhibitor remains unclear. We present a series of eight
      patients with ALK-rearranged NSCLC treated with alectinib who experienced disease
      progression after ceritinib. Both crizotinib and ceritinib were administered to
      six patients, with four (29%) patients receiving crizotinib followed by
      ceritinib. Among the eight study patients, two (25%) had partial response, one
      (12%) stable disease, and five (63%) had progressive disease. The median
      progression-free survival was 3.6 months (95% confidence interval=0-7.1 months).
      The results of this study suggest that the second-generation ALK inhibitor
      alectinib has limited efficacy after initial treatment with the second-generation
      ALK inhibitor ceritinib.

PMID- 29061838
TI  - Erratum.

PMID- 29061839
TI  - Retraction.

PMID- 29061841
TI  - Correction to: ICES (Intraoperative Stereotactic Computed Tomography-Guided
      Endoscopic Surgery) for Brain Hemorrhage: A Multicenter Randomized Controlled
      Trial.

PMID- 29061843
TI  - Temporal trends in cardiovascular disease risk factor profiles in a population
      based schizophrenia sample: a repeat cross-sectional study.
AB  - BACKGROUND: People with schizophrenia have an increased burden of cardiovascular
      diseases (CVD); however, little is known about the cardiovascular risk factor
      profiles of non-institutionalised individuals with schizophrenia. This study
      estimated the prevalence of CVD risk factors in a population-based sample of
      Canadians with and without schizophrenia. METHODS: Ontario respondents of the
      Canadian Community Health Survey were linked to administrative health databases;
      using a validated algorithm, we identified 1103 non-institutionalised individuals
      with schizophrenia and 156 376 without schizophrenia. We examined the prevalence
      of eight CVD risk factors: smoking, diabetes, hypertension, obesity, physical
      inactivity, fruit/vegetables consumption, psychosocial stress and binge drinking.
      To examine temporal trends, we compared prevalence estimates from 2001-2005 to
      2007-2010. RESULTS: The prevalence of most CVD risk factors was significantly
      higher among those with schizophrenia than the general population. Obesity and
      diabetes prevalence increased by 39% and 71%, respectively, in the schizophrenia
      group vs 11% and 24%, respectively, in the non-schizophrenia group between the
      two time periods. Unlike the general population, smoking rates among those with
      schizophrenia did not decline. Almost 90% of individuals with schizophrenia had
      at least one CVD risk factor and almost 40% had >=3 co-occurring risk factors.
      CONCLUSION: Individuals with schizophrenia had a greater prevalence of individual
      and multiple CVD risk factors compared with those without schizophrenia, which
      persisted over time. Our findings suggest that public health efforts to reduce
      the burden of CVD risk factors have not been as effective in the schizophrenia
      population, thus highlighting the need for more targeted interventions and
      prevention strategies.

PMID- 29061844
TI  - Alcohol control policies and alcohol consumption: an international comparison of
      167 countries.
AB  - BACKGROUND: Alcohol control policy has a fundamental role in limiting negative
      health, economic and social harm caused by alcohol consumption. However, there is
      substantial international heterogeneity in country-level policy adoption,
      implementation and monitoring. Comparative measures so far focused on Europe or
      the Organisation for Economic Co-operation and Development countries. METHODS: We
      created an Alcohol Control Policy Index (ACPI) for 167 countries using five
      different methodological approaches. National policies were sourced from WHO's
      Global Information System on Alcohol and Health. We assessed ACPI's criterion
      related validity by calculating the strength of the association among the
      different approaches. As for content validity, we tested whether the resulting
      scores explained variations in alcohol per capita consumption cross-nationally,
      controlling for gross domestic product, population age, urbanisation and world
      region using OLS and random coefficients models. RESULTS: Index scores and ranks
      from different methodological approaches are highly correlated (r=0.99). Higher
      scores were associated with lower consumption across the five methods. For each 1
      score increase in the ACPI, the reduction in per capita alcohol consumption
      varies from -0.024 L (95% CI (-0.043 to -0.004) to -0.014 L (95% CI (-0.034 to
      0.005). We obtain larger coefficients and p values <0.005 when estimating random
      coefficients. CONCLUSION: ACPI offers a measure of alcohol control policy across
      countries that makes use of a larger number of countries than its predecessors,
      as well as a wider range of methodologies for its calculation, both of which
      contribute to its validity. Furthermore, it shows that the statutory strictness
      of alcohol control policies is associated with lower levels of alcohol
      consumption.

PMID- 29061842
TI  - Endothelial nitric oxide synthase modulates Toll-like receptor 4-mediated IL-6
      production and permeability via nitric oxide-independent signaling.
AB  - Endothelial dysfunction, characterized by changes in eNOS, is a common finding in
      chronic inflammatory vascular diseases. These states are associated with
      increased infectious complications. We hypothesized that alterations in eNOS
      would enhance the response to LPS-mediated TLR4 inflammation. Human microvascular
      endothelial cells were treated with sepiapterin or N-nitro-L-arginine methylester
      (L-NAME) to alter endogenous NO production, and small interfering RNA to
      knockdown eNOS. Alterations of endogenous NO by sepiapterin, and L-NAME provided
      no significant changes to LPS inflammation. In contrast, eNOS knockdown greatly
      enhanced endothelial IL-6 production and permeability in response to LPS.
      Knockdown of eNOS enhanced LPS-induced p38. Inhibition of p38 with SB203580
      prevented IL-6 production, without altering permeability. Knockdown of p38
      impaired NF-kappaB activation. Physical interaction between p38 and eNOS was
      demonstrated by immunoprecipitation, suggesting a novel, NO-independent mechanism
      for eNOS regulation of TLR4. In correlation, biopsy samples in patients with
      systemic lupus erythematous showed reduced eNOS expression with associated
      elevations in TLR4 and p38, suggesting an in vivo link. Thus, reduced expression
      of eNOS, as seen in chronic inflammatory disease, was associated with enhanced
      TLR4 signaling through p38. This may enhance the response to infection in
      patients with chronic inflammatory conditions.-Stark, R. J., Koch, S. R., Choi,
      H., Mace, E. H., Dikalov, S. I., Sherwood, E. R., Lamb, F. S. Endothelial nitric
      oxide synthase modulates Toll-like receptor 4-mediated IL-6 production and
      permeability via nitric oxide-independent signaling.

PMID- 29061845
TI  - Influence of affordability of alcohol on educational disparities in alcohol
      related mortality in Finland and Sweden: a time series analysis.
AB  - BACKGROUND: Prices of alcohol and income tend to influence how much people buy
      and consume alcohol. Price and income may be combined into one measure,
      affordability of alcohol. Research on the association between affordability of
      alcohol and alcohol-related harm is scarce. Furthermore, no research exists on
      how this association varies across different subpopulations. We estimated the
      effects of affordability of alcohol on alcohol-related mortality according to
      gender and education in Finland and Sweden. METHODS: Vector-autoregressive time
      series modelling was applied to the quarter-annual aggregations of alcohol
      related deaths and affordability of alcohol in Finland in 1988-2007 and in Sweden
      in 1991-2008. Alcohol-related mortality was defined using information on both
      underlying and contributory causes of death. We calculated affordability of
      alcohol index using information on personal taxable income and prices of various
      types of alcohol. RESULTS: Among Finnish men with secondary education, an
      increase of 1% in the affordability of total alcohol was associated with an
      increase of 0.028% (95% CI 0.004 to 0.053) in alcohol-related mortality. Similar
      associations were also found for affordability for various types of alcohol and
      for beer only in the lowest education group. We found few other significant
      positive associations for other subpopulations in Finland or Sweden. However,
      reverse associations were found among secondary-educated Swedish women.
      CONCLUSIONS: Overall, the associations between affordability of alcohol and
      alcohol-related mortality were relatively weak. Increased affordability of total
      alcoholic beverages was associated with higher rates of alcohol-related mortality
      only among Finnish men with secondary education.

PMID- 29061846
TI  - A transcriptional coregulator, SPIN.DOC, attenuates the coactivator activity of
      Spindlin1.
AB  - Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in
      embryonic development and emerging roles in cancer. SPIN1 harbors three Tudor
      domains, two of which engage the tail of histone H3 by reading the H3-Lys-4
      trimethylation and H3-Arg-8 asymmetric dimethylation marks. To gain mechanistic
      insight into how SPIN1 functions as a transcriptional coactivator, here we
      purified its interacting proteins. We identified an uncharacterized protein
      (C11orf84), which we renamed SPIN1 docking protein (SPIN.DOC), that directly
      binds SPIN1 and strongly disrupts its histone methylation reading ability,
      causing it to disassociate from chromatin. The Spindlin family of coactivators
      has five related members (SPIN1, 2A, 2B, 3, and 4), and we found that all of them
      bind SPIN.DOC. It has been reported previously that SPIN1 regulates gene
      expression in the Wnt signaling pathway by directly interacting with
      transcription factor 4 (TCF4). We observed here that SPIN.DOC associates with
      TCF4 in a SPIN1-dependent manner and dampens SPIN1 coactivator activity in
      TOPflash reporter assays. Furthermore, knockdown and overexpression experiments
      indicated that SPIN.DOC represses the expression of a number of SPIN1-regulated
      genes, including those encoding ribosomal RNA and the cytokine IL1B. In
      conclusion, we have identified SPIN.DOC as a transcriptional repressor that binds
      SPIN1 and masks its ability to engage the H3-Lys-4 trimethylation activation
      mark.

PMID- 29061848
TI  - A herpesvirus entry mediator mutein with selective agonist action for the
      inhibitory receptor B and T lymphocyte attenuator.
AB  - The human cytomegalovirus opening reading frame UL144 is an ortholog of the TNF
      receptor superfamily member, herpesvirus entry mediator (HVEM; TNFRSF14). HVEM
      binds the TNF ligands, LIGHT and LTa; the immunoglobulin inhibitory receptor, B
      and T lymphocyte attenuator (BTLA); and the natural killer cell-activating
      receptor CD160. However, UL144 selectively binds BTLA, avoiding activation of
      inflammatory signaling initiated by CD160 in natural killer cells. BTLA and CD160
      cross-compete for binding HVEM, but the structural basis for the ligand
      selectivity by UL144 and how it acts as an anti-inflammatory agonist remains
      unclear. Here, we modeled the UL144 structure and characterized its binding with
      BTLA. The UL144 structure was predicted to closely mimic the surface of HVEM, and
      we also found that both HVEM and UL144 bind a common epitope of BTLA, whether
      engaged in trans or in cis, that is shared with a BTLA antibody agonist. On the
      basis of the UL144 selectivity, we engineered a BTLA-selective HVEM protein to
      understand the basis for ligand selectivity and BTLA agonism to develop novel
      anti-inflammatory agonists. This HVEM mutein did not bind CD160 or TNF ligands
      but did bind BTLA with 10-fold stronger affinity than wild-type HVEM and retained
      potent inhibitory activity that reduced T-cell receptor, B-cell receptor, and
      interferon signaling in B cells. In conclusion, using a viral immune evasion
      strategy that shows broad immune-ablating activity, we have identified a novel
      anti-inflammatory BTLA-selective agonist.

PMID- 29061849
TI  - The small molecule luteolin inhibits N-acetyl-alpha-galactosaminyltransferases
      and reduces mucin-type O-glycosylation of amyloid precursor protein.
AB  - Mucin-type O-glycosylation is the most abundant type of O-glycosylation. It is
      initiated by the members of the polypeptide N-acetyl-alpha
      galactosaminyltransferase (ppGalNAc-T) family and closely associated with both
      physiological and pathological conditions, such as coronary artery disease or
      Alzheimer's disease. The lack of direct and selective inhibitors of ppGalNAc-Ts
      has largely impeded research progress in understanding the molecular events in
      mucin-type O-glycosylation. Here, we report that a small molecule, the plant
      flavonoid luteolin, selectively inhibits ppGalNAc-Ts in vitro and in cells. We
      found that luteolin inhibits ppGalNAc-T2 in a peptide/protein-competitive manner
      but not promiscuously (e.g. via aggregation-based activity). X-ray structural
      analysis revealed that luteolin binds to the PXP motif-binding site found in most
      protein substrates, which was further validated by comparing the interactions of
      luteolin with wild-type enzyme and with mutants using 1H NMR-based binding
      experiments. Functional studies disclosed that luteolin at least partially
      reduced production of beta-amyloid protein by selectively inhibiting the activity
      of ppGalNAc-T isoforms. In conclusion, our study provides key structural and
      functional details on luteolin inhibiting ppGalNAc-T activity, opening up the way
      for further optimization of more potent and specific ppGalNAc-T inhibitors.
      Moreover, our findings may inform future investigations into site-specific O
      GalNAc glycosylation and into the molecular mechanism of luteolin-mediated
      ppGalNAc-T inhibition.

PMID- 29061847
TI  - Discovery of alpha-l-arabinopyranosidases from human gut microbiome expands the
      diversity within glycoside hydrolase family 42.
AB  - Enzymes of the glycoside hydrolase family 42 (GH42) are widespread in bacteria of
      the human gut microbiome and play fundamental roles in the decomposition of both
      milk and plant oligosaccharides. All GH42 enzymes characterized so far have beta
      galactosidase activity. Here, we report the existence of a GH42 subfamily that is
      exclusively specific for alpha-l-arabinopyranoside and describe the first
      representative of this subfamily. We found that this enzyme (BlArap42B) from a
      probiotic Bifidobacterium species cannot hydrolyze beta-galactosides. However,
      BlArap42B effectively hydrolyzed paeonolide and ginsenoside Rb2, plant glycosides
      containing an aromatic aglycone conjugated to alpha-l-arabinopyranosyl-(1,6)-beta
      d-glucopyranoside. Paeonolide, a natural glycoside from the roots of the plant
      genus Paeonia, is not hydrolyzed by classical GH42 beta-galactosidases. X-ray
      crystallography revealed a unique Trp345-X12-Trp358 sequence motif at the
      BlArap42B active site, as compared with a Phe-X12-His motif in classical GH42
      beta-galactosidases. This analysis also indicated that the C6 position of
      galactose is blocked by the aromatic side chains, hence allowing accommodation
      only of Arap lacking this carbon. Automated docking of paeonolide revealed that
      it can fit into the BlArap42B active site. The Glcp moiety of paeonolide stacks
      onto the aromatic ring of the Trp252 at subsite +1 and C4-OH is hydrogen bonded
      with Asp249 Moreover, the aglycone stacks against Phe421 from the neighboring
      monomer in the BlArap42B trimer, forming a proposed subsite +2. These results
      further support the notion that evolution of metabolic specialization can be
      tracked at the structural level in key enzymes facilitating degradation of
      specific glycans in an ecological niche.

PMID- 29061850
TI  - The Brucella effector protein TcpB induces degradation of inflammatory caspases
      and thereby subverts non-canonical inflammasome activation in macrophages.
AB  - The inflammasome contains intracellular receptors that recognize various pathogen
      associated molecular patterns and play crucial roles in innate immune responses
      to invading pathogens. Non-canonical inflammasome activation is mediated by
      caspase-4/11, which recognizes intracellular LPS and promotes pyroptosis and
      secretion of proinflammatory cytokines. Brucella species are infectious
      intracellular pathogens that replicate in professional and non-professional
      phagocytic cells and subvert immune responses for chronic persistence in the
      host. The Brucella effector protein TcpB suppresses Toll-like receptor 2 (TLR2)-
      and TLR4-mediated innate immune responses by targeted degradation of the
      Toll/interleukin-1 receptor (TIR) domain-containing adaptor protein. TcpB is a
      cell-permeable protein with multiple functions, and its intracellular targets
      other than TIR domain-containing adaptor protein remain unclear. Here, we report
      that TcpB induces ubiquitination and degradation of the inflammatory caspases 1,
      4, and 11. Furthermore, in both mouse and human macrophages, TcpB attenuated LPS
      induced non-canonical inflammasome activation and suppressed pyroptosis and
      secretion of IL-1alpha and IL-1beta induced by intracellular LPS delivery. The
      intact TIR domain was essential for TcpB to subvert the non-canonical
      inflammasome activation as a TcpB(G158A) mutant failed to suppress pyroptotic
      cell death and inflammatory responses. Brucella-infected macrophages exhibited
      minimal pyroptosis but secreted IL-1beta, which was suppressed by TcpB. We also
      demonstrated that TcpB protein can efficiently attenuate Salmonella enterica
      serovar Typhimurium-induced pyroptosis and proinflammatory cytokine secretion in
      macrophages. Because TcpB suppresses both TLR4- and caspase-4/11-mediated
      inflammation, TcpB might be a candidate target for developing drugs against LPS
      induced septicemia.

PMID- 29061851
TI  - Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface
      glycoprotein expression in humans but not mice.
AB  - PD-L1 (programmed death ligand 1) and PD-L2 are cell-surface glycoproteins that
      interact with programmed death 1 (PD-1) on T cells to attenuate inflammation. PD
      1 signaling has attracted intense interest for its role in a pathophysiological
      context: suppression of anti-tumor immunity. Similarly, vitamin D signaling has
      been increasingly investigated for its non-classical actions in stimulation of
      innate immunity and suppression of inflammatory responses. Here, we show that
      hormonal 1,25-dihydroxyvitamin D (1,25D) is a direct transcriptional inducer of
      the human genes encoding PD-L1 and PD-L2 through the vitamin D receptor, a ligand
      regulated transcription factor. 1,25D stimulated transcription of the gene
      encoding PD-L1 in epithelial and myeloid cells, whereas the gene encoding the
      more tissue-restricted PD-L2 was regulated only in myeloid cells. We identified
      and characterized vitamin D response elements (VDREs) located in both genes and
      showed that 1,25D treatment induces cell-surface expression of PD-L1 in
      epithelial and myeloid cells. In co-culture experiments with primary human T
      cells, epithelial cells pretreated with 1,25D suppressed activation of CD4+ and
      CD8+ cells and inhibited inflammatory cytokine production in a manner that was
      abrogated by anti-PD-L1 blocking antibody. Consistent with previous observations
      of species-specific regulation of immunity by vitamin D, the VDREs are present in
      primate genes, but neither the VDREs nor the regulation by 1,25D is present in
      mice. These findings reinforce the physiological role of 1,25D in controlling
      inflammatory immune responses but may represent a double-edged sword, as they
      suggest that elevated vitamin D signaling in humans could suppress anti-tumor
      immunity.

PMID- 29061852
TI  - Structural basis for the differential interaction of Scribble PDZ domains with
      the guanine nucleotide exchange factor beta-PIX.
AB  - Scribble is a highly conserved protein regulator of cell polarity that has been
      demonstrated to function as a tumor suppressor or, conversely, as an oncogene in
      a context-dependent manner, and it also controls many physiological processes
      ranging from immunity to memory. Scribble consists of a leucine-rich repeat
      domain and four PDZ domains, with the latter being responsible for most of
      Scribble's complex formation with other proteins. Given the similarities of the
      Scribble PDZ domain sequences in their binding grooves, it is common for these
      domains to show overlapping preferences for the same ligand. Yet, Scribble PDZ
      domains can still exhibit unique binding profiles toward other ligands. This
      raises the fundamental question as to how these PDZ domains discriminate ligands
      and exert specificities in Scribble complex formation. To better understand how
      Scribble PDZ domains direct cell polarity signaling, we investigated here their
      interactions with the well-characterized Scribble binding partner beta-PIX, a
      guanine nucleotide exchange factor. We report the interaction profiles of all
      isolated Scribble PDZ domains with a beta-PIX peptide. We show that Scribble PDZ1
      and PDZ3 are the major interactors with beta-PIX and reveal a distinct binding
      hierarchy in the interactions between the individual Scribble PDZ domains and
      beta-PIX. Furthermore, using crystal structures of PDZ1 and PDZ3 bound to beta
      PIX, we define the structural basis for Scribble's ability to specifically engage
      beta-PIX via its PDZ domains and provide a mechanistic platform for understanding
      Scribble-beta-PIX-coordinated cellular functions such as directional cell
      migration.

PMID- 29061853
TI  - Factors associated with disease progression in early-diagnosed pulmonary arterial
      hypertension associated with systemic sclerosis: longitudinal data from the
      DETECT cohort.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a severe complication of
      systemic sclerosis (SSc). In this longitudinal study, we aimed to identify
      factors associated with an unfavourable outcome in patients with SSc with early
      PAH (SSc-PAH) from the DETECT cohort. METHODS: Patients with SSc-PAH enrolled in
      DETECT were observed for up to 3 years. Associations between cross-sectional
      variables and disease progression (defined as the occurrence of any of the
      following events: WHO Functional Class worsening, combination therapy for PAH,
      hospitalisation or death) were analysed by univariable logistic regression.
      RESULTS: Of 57 patients with PAH (median observation time 12.6 months), 25
      (43.9%) had disease progression. The following factors (OR (95% CI)) were
      associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced
      vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)%
      predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6))
      and low DLCO% predicted (non-linear relationship). CONCLUSION: More than 40% of
      early-diagnosed patients with SSc-PAH had disease progression during a short
      follow-up time, with male gender, functional capacity and pulmonary function
      tests at PAH diagnosis being associated with progression. This suggests that even
      mild PAH should be considered a high-risk complication of SSc.

PMID- 29061854
TI  - Canadian funders and institutions are lagging on reporting results of clinical
      trials.

PMID- 29061856
TI  - Legionellosis following water birth in a hot tub in a Canadian neonate.

PMID- 29061855
TI  - Depression and mortality in a longitudinal study: 1952-2011.
AB  - BACKGROUND: Many studies have shown that depression increases mortality risk. We
      aimed to investigate the duration of time over which depression is associated
      with increased risk of mortality, secular trends in the association between
      depression and mortality, and sex differences in the association between
      depression and mortality. METHODS: We conducted a cohort study of 3410 adults
      enrolled in 3 representative samples of a county in Atlantic Canada in 1952 (n =
      1003), 1970 (n = 1203) or 1992 (n = 1402) (the Stirling County Study). Depression
      was measured using a diagnostic algorithm based on the presence of depressed mood
      and associated symptoms, duration of more than 1 month, and substantial
      impairment. Vital status of participants through 2011 was determined using
      probabilistic linkages to the Canadian Mortality Database. RESULTS: Depression
      was associated with a heightened risk of mortality among men during the 3 time
      periods of the study, with hazard ratios (HRs) of 2.90 (95% confidence interval
      [CI] 1.69-4.98) between 1952 and 1967, 1.97 (CI 1.34-2.89) between 1968 and 1990,
      and 1.52 (CI 1.09-2.13) between 1991 and 2011. Elevated risk of mortality was
      noted among women only between 1990 and 2011 (HR = 1.51; CI = 1.11-2.05).
      INTERPRETATION: The association between depression and mortality persists over
      long periods of time and has emerged among women in recent decades, despite
      contemporaneous improvements in the treatment of depression and reduction of
      stigma associated with depression. Further research is needed to better
      understand the mechanisms involved.

PMID- 29061857
TI  - A case of blood sweating: hematohidrosis syndrome.

PMID- 29061858
TI  - Opioid warning label.

PMID- 29061859
TI  - Response to "Opioid warning label".

PMID- 29061861
TI  - Rich nations are feeding research predators.

PMID- 29061860
TI  - COPD research and treatment pioneer.

PMID- 29061862
TI  - Researchers may be part of the problem in predatory publishing.

PMID- 29061863
TI  - Body temperature and cold sensation during and following exercise under temperate
      room conditions in cold-sensitive young trained females.
AB  - We evaluated cold sensation at rest and in response to exercise-induced changes
      in core and skin temperatures in cold-sensitive exercise trained females. Fifty
      eight trained young females were screened by a questionnaire, selecting cold
      sensitive (Cold-sensitive, n = 7) and non-cold-sensitive (Control, n = 7)
      individuals. Participants rested in a room at 29.5 degrees C for ~100 min after
      which ambient temperature was reduced to 23.5 degrees C where they remained
      resting for 60 min. Participants then performed 30-min of moderate intensity
      cycling (50% peak oxygen uptake) followed by a 60-min recovery. Core and mean
      skin temperatures and cold sensation over the whole-body and extremities (fingers
      and toes) were assessed throughout. Resting core temperature was lower in the
      Cold-sensitive relative to Control group (36.4 +/- 0.3 vs. 36.7 +/- 0.2 degrees
      C). Core temperature increased to similar levels at end-exercise (~37.2 degrees
      C) and gradually returned to near preexercise rest levels at the end of recovery
      (>36.6 degrees C). Whole-body cold sensation was greater in the Cold-sensitive
      relative to Control group during resting at a room temperature of 23.5 degrees C
      only without a difference in mean skin temperature between groups. In contrast,
      cold sensation of the extremities was greater in the Cold-sensitive group prior
      to, during and following exercise albeit this was not paralleled by differences
      in mean extremity skin temperature. We show that young trained females who are
      sensitive to cold exhibit augmented whole-body cold sensation during rest under
      temperate ambient conditions. However, this response is diminished during and
      following exercise. In contrast, cold sensation of extremities is augmented
      during resting that persists during and following exercise.

PMID- 29061864
TI  - Alveolar air and oxidative metabolic demand during exercise in healthy adults:
      the role of single-nucleotide polymorphisms of the beta2AR gene.
AB  - The predominating beta-adrenergic receptor subtype expressed on human alveolar
      tissue is the beta2AR The homozygous arginine (Arg16Arg) single-nucleotide
      polymorphism (SNP) at codon 16 of the beta2AR gene has been associated with
      abnormal beta2AR function accompanied by decreased resting alveolar-capillary
      membrane gas-transfer in certain healthy adults. Although not previously studied
      in the context of the beta2AR gene, pulmonary gas-transfer is also influenced by
      alveolar volume (VA) and with it the availability of alveolar surface area,
      particularly during exercise. Small VA implies less alveolar surface area
      available for O2 transport. We tested the following hypothesis in healthy adults
      during exercise: compared with Gly16Gly and Arg16Gly beta2AR genotypes, Arg16Arg
      will demonstrate reduced VA and ventilation (VA) relative to VE and oxidative
      metabolic demand. Age- BMI- and gender-matched groups of Arg16Arg (N = 16),
      Gly16Gly (N = 31), and Arg16Gly (N = 17) performed consecutive low (9-min, 40%
      peak workload) and moderate (9-min, 75%-peak workload) intensity exercise. We
      derived VA and VA using "ideal" alveolar equations via arterialized gases
      combined with breath-by-breath ventilation and gas-exchange measurements; whereas
      steady-state VO2 was used in metabolic equations to derive exercise economy (EC =
      workload/VO2). Variables at rest did not differ across beta2AR genotype.
      Strongest beta2AR genotype effects occurred during moderate exercise.
      Accordingly, while VE did not differ across genotype (P > 0.05), decreased in
      Arg16Arg versus Arg16Gly and Gly16Gly were VO2 (1110 +/- 263, 1269 +/- 221, 1300
      +/- 319 mL/(min.m2), respectively, both P < 0.05), VA (59 +/- 21, 70 +/- 16, 70
      +/- 21 L/min, respectively, both P < 0.05), and VA (1.43 +/- 0.37, 1.95 +/- 0.61,
      1.93 +/- 0.65 L, respectively, both P < 0.05). Also reduced was EC in Arg16Arg
      versus Arg16Gly (P < 0.05) and Gly16Gly (P > 0.05) (1.81 +/- 0.23, 1.99 +/- 0.30,
      and 1.94 +/- 0.26 kcal/(L.m2), respectively). Compared with Gly16Gly and Arg16Gly
      genotypes, these data suggest the Arg16Arg beta2AR genotype plays a role in the
      loss of oxidative metabolic efficiency coupled with an inadaptive VA and, hence,
      smaller alveolar surface area available for O2 transport during submaximal
      exercise in healthy adults.

PMID- 29061865
TI  - Prolonged leg bending impairs endothelial function in the popliteal artery.
AB  - Uninterrupted sitting blunts vascular endothelial function in the lower
      extremities; however, the factors contributing to this impairment remain largely
      unknown. Herein, we tested the hypothesis that prolonged flexion of the hip and
      knee joints, as it occurs during sitting, and associated low shear stress and
      disturbed (i.e., turbulent) blood flow caused by arterial bending, impairs
      endothelial function at the popliteal artery. Bilateral measurements of popliteal
      artery flow-mediated dilation (FMD) were performed in 12 healthy subjects before
      and after a 3-h lying-down period during which one leg was bent (i.e., 90-degree
      angles at the hip and knee) and the contralateral leg remained straight, serving
      as internal control. During the 3-h lying down period, the bent leg displayed a
      profound and sustained reduction in popliteal artery blood flow and mean shear
      rate; whereas a slight but steady decline that only became significant at 3 h was
      noted in the straight leg. Notably, 3 h of lying down markedly impaired popliteal
      artery FMD in the bent leg (pre: 6.3 +/- 1.2% vs. post: 2.8 +/- 0.91%; P < 0.01)
      but not in the straight leg (pre: 5.6 +/- 1.1% vs. post: 7.1 +/- 1.2%; P = 0.24).
      Collectively, this study provides evidence that prolonged bending of the leg
      causes endothelial dysfunction in the popliteal artery. This effect is likely
      secondary to vascular exposure to low and disturbed blood flow resulting from
      arterial angulation. We conclude that spending excessive time with legs bent and
      immobile, irrespective of whether this is in the setting of sitting or lying
      down, may be disadvantageous for leg vascular health.

PMID- 29061866
TI  - A Tripartite Amplification Loop Involving the Transcription Factor WRKY75,
      Salicylic Acid, and Reactive Oxygen Species Accelerates Leaf Senescence.
AB  - Leaf senescence is a highly coordinated, complicated process involving the
      integration of numerous internal and environmental signals. Salicylic acid (SA)
      and reactive oxygen species (ROS) are two well-defined inducers of leaf
      senescence whose contents progressively and interdependently increase during leaf
      senescence via an unknown mechanism. Here, we characterized the transcription
      factor WRKY75 as a positive regulator of leaf senescence in Arabidopsis thaliana.
      Knockdown or knockout of WRKY75 delayed age-dependent leaf senescence, while
      overexpression of WRKY75 accelerated this process. WRKY75 transcription is
      induced by age, SA, H2O2, and multiple plant hormones. Meanwhile, WRKY75 promotes
      SA production by inducing the transcription of SA INDUCTION-DEFICIENT2 (SID2) and
      suppresses H2O2 scavenging, partly by repressing the transcription of CATALASE2
      (CAT2). Genetic analysis revealed that the mutation of SID2 or an increase in
      catalase activity rescued the precocious leaf senescence phenotype evoked by
      WRKY75 overexpression. Based on these results, we propose a tripartite
      amplification loop model in which WRKY75, SA, and ROS undergo a gradual but self
      sustained rise driven by three interlinking positive feedback loops. This
      tripartite amplification loop provides a molecular framework connecting upstream
      signals, such as age and plant hormones, to the downstream regulatory network
      executed by SA- and H2O2-responsive transcription factors during leaf senescence.

PMID- 29061867
TI  - ZEITLUPE Contributes to a Thermoresponsive Protein Quality Control System in
      Arabidopsis.
AB  - Cellular proteins undergo denaturation and oxidative damage under heat stress,
      forming insoluble aggregates that are toxic to cells. Plants possess versatile
      mechanisms to deal with insoluble protein aggregates. Denatured proteins are
      either renatured to their native conformations or removed from cellular
      compartments; these processes are often referred to as protein quality control.
      Heat shock proteins (HSPs) act as molecular chaperones that assist in the
      renaturation-degradation process. However, how protein aggregates are cleared
      from cells in plants is largely unknown. Here, we demonstrate that heat-induced
      protein aggregates are removed by a protein quality control system that includes
      the ZEITLUPE (ZTL) E3 ubiquitin ligase, a central circadian clock component in
      Arabidopsis thaliana ZTL mediates the polyubiquitination of aggregated proteins,
      which leads to proteasomal degradation and enhances the thermotolerance of plants
      growing at high temperatures. The ZTL-defective ztl-105 mutant exhibited reduced
      thermotolerance, which was accompanied by a decline in polyubiquitination but an
      increase in protein aggregate formation. ZTL and its interacting partner HSP90
      were cofractionated with insoluble aggregates under heat stress, indicating that
      ZTL contributes to the thermoresponsive protein quality control machinery.
      Notably, the circadian clock was hypersensitive to heat in ztl-105 We propose
      that ZTL-mediated protein quality control contributes to the thermal stability of
      the circadian clock.

PMID- 29061869
TI  - Infection Prevention and Control in Pediatric Ambulatory Settings.
AB  - Since the American Academy of Pediatrics published its statement titled
      "Infection Prevention and Control in Pediatric Ambulatory Settings" in 2007,
      there have been significant changes that prompted this updated statement.
      Infection prevention and control is an integral part of pediatric practice in
      ambulatory medical settings as well as in hospitals. Infection prevention and
      control practices should begin at the time the ambulatory visit is scheduled. All
      health care personnel should be educated regarding the routes of transmission and
      techniques used to prevent the transmission of infectious agents. Policies for
      infection prevention and control should be written, readily available, updated
      every 2 years, and enforced. Many of the recommendations for infection control
      and prevention from the Centers for Disease Control and Prevention for
      hospitalized patients are also applicable in the ambulatory setting. These
      recommendations include requirements for pediatricians to take precautions to
      identify and protect employees likely to be exposed to blood or other potentially
      infectious materials while on the job. In addition to emphasizing the key
      principles of infection prevention and control in this policy, we update those
      that are relevant to the ambulatory care patient. These guidelines emphasize the
      role of hand hygiene and the implementation of diagnosis- and syndrome-specific
      isolation precautions, with the exemption of the use of gloves for routine diaper
      changes and wiping a well child's nose or tears for most patient encounters.
      Additional topics include respiratory hygiene and cough etiquette strategies for
      patients with a respiratory tract infection, including those relevant for special
      populations like patients with cystic fibrosis or those in short-term residential
      facilities; separation of infected, contagious children from uninfected children
      when feasible; safe handling and disposal of needles and other sharp medical
      devices; appropriate use of personal protective equipment, such as gloves, gowns,
      masks, and eye protection; and appropriate use of sterilization, disinfection,
      and antisepsis. Lastly, in this policy, we emphasize the importance of public
      health interventions, including vaccination for patients and health care
      personnel, and outline the responsibilities of the health care provider related
      to prompt public health notification for specific reportable diseases and
      communication with colleagues who may be providing subsequent care of an infected
      patient to optimize the use of isolation precautions and limit the spread of
      contagions.

PMID- 29061870
TI  - Sexual and Reproductive Health Care Services in the Pediatric Setting.
AB  - Pediatricians are an important source of health care for adolescents and young
      adults and can play a significant role in addressing their patients' sexual and
      reproductive health needs, including preventing unintended pregnancies and
      sexually transmitted infections (STIs), including HIV, and promoting healthy
      relationships. STIs, HIV, and unintended pregnancy are all preventable health
      outcomes with potentially serious permanent sequelae; the highest rates of STIs,
      HIV, and unintended pregnancy are reported among adolescents and young adults.
      Office visits present opportunities to provide comprehensive education and health
      care services to adolescents and young adults to prevent STIs, HIV, and
      unintended pregnancies. The American Academy of Pediatrics, other professional
      medical organizations, and the government have guidelines and recommendations
      regarding the provision of sexual and reproductive health information and
      services. However, despite these recommendations, recent studies have revealed
      that there is substantial room for improvement in actually delivering the
      recommended services. The purpose of this clinical report is to assist
      pediatricians to operationalize the provision of various aspects of sexual and
      reproductive health care into their practices and to provide guidance on
      overcoming barriers to providing this care routinely while maximizing
      opportunities for confidential health services delivery in their offices.

PMID- 29061871
TI  - Drinking Water to Prevent Postvaccination Presyncope in Adolescents: A Randomized
      Trial.
AB  - BACKGROUND AND OBJECTIVES: Postvaccination syncope can cause injury. Drinking
      water prephlebotomy increases peripheral vascular tone, decreasing risk of blood
      donation presyncope and syncope. This study evaluated whether drinking water
      prevaccination reduces postvaccination presyncope, a potential syncope precursor.
      METHODS: We conducted a randomized trial of subjects aged 11 to 21 years
      receiving >=1 intramuscular vaccine in primary care clinics. Intervention
      subjects were encouraged to drink 500 mL of water, with vaccination recommended
      10 to 60 minutes later. Control subjects received usual care. Presyncope symptoms
      were assessed with a 12-item survey during the 20-minutes postvaccination.
      Symptoms were classified with a primary cutoff sensitive for presyncope, and a
      secondary, more restrictive cutoff requiring greater symptoms. Results were
      adjusted for clustering by recruitment center. RESULTS: There were 906 subjects
      randomly assigned to the control group and 901 subjects randomly assigned to the
      intervention group. None had syncope. Presyncope occurred in 36.2% of subjects by
      using the primary definition, and in 8.0% of subjects by using the restrictive
      definition. There were no significant differences in presyncope by intervention
      group for the primary (1-sided test, P = .24) or restrictive outcome (1-sided
      test, P = .17). Among intervention subjects vaccinated within 10 to 60 minutes
      after drinking all 500 mL of water (n = 519), no reduction in presyncope was
      observed for the primary or restrictive outcome (1-sided tests, P = .13, P =
      .17). In multivariable regression analysis, presyncope was associated with
      younger age, history of passing out or nearly passing out after a shot or blood
      draw, prevaccination anxiety, receiving >1 injected vaccine, and greater
      postvaccination pain. CONCLUSIONS: Drinking water before vaccination did not
      prevent postvaccination presyncope. Predictors of postvaccination presyncope
      suggest opportunities for presyncope and syncope prevention interventions.

PMID- 29061872
TI  - Medical Cannabinoids in Children and Adolescents: A Systematic Review.
AB  - CONTEXT: Legalization of medical marijuana in many states has led to a widening
      gap between the accessibility and the evidence for cannabinoids as a medical
      treatment. OBJECTIVE: To systematically review published reports to identify the
      evidence base of cannabinoids as a medical treatment in children and adolescents.
      DATA SOURCES: Based on Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines, a search of PubMed, Medline, and the Cumulative Index to
      Nursing and Allied Health Literature databases was conducted in May 2017. STUDY
      SELECTION: Searching identified 2743 citations, and 103 full texts were reviewed.
      DATA EXTRACTION: Searching identified 21 articles that met inclusion criteria,
      including 22 studies with a total sample of 795 participants. Five randomized
      controlled trials, 5 retrospective chart reviews, 5 case reports, 4 open-label
      trials, 2 parent surveys, and 1 case series were identified. RESULTS: Evidence
      for benefit was strongest for chemotherapy-induced nausea and vomiting, with
      increasing evidence of benefit for epilepsy. At this time, there is insufficient
      evidence to support use for spasticity, neuropathic pain, posttraumatic stress
      disorder, and Tourette syndrome. LIMITATIONS: The methodological quality of
      studies varied, with the majority of studies lacking control groups, limited by
      small sample size, and not designed to test for the statistical significance of
      outcome measures. Studies were heterogeneous in the cannabinoid composition and
      dosage and lacked long-term follow-up to identify potential adverse effects.
      CONCLUSIONS: Additional research is needed to evaluate the potential role of
      medical cannabinoids in children and adolescents, especially given increasing
      accessibility from state legalization and potential psychiatric and
      neurocognitive adverse effects identified from studies of recreational cannabis
      use.

PMID- 29061873
TI  - Solving yeast jigsaw puzzles over a glass of wine: Synthetic genome engineering
      pioneers new possibilities for wine yeast research.

PMID- 29061868
TI  - Reciprocally Retained Genes in the Angiosperm Lineage Show the Hallmarks of
      Dosage Balance Sensitivity.
AB  - In several organisms, particular functional categories of genes, such as
      regulatory and complex-forming genes, are preferentially retained after whole
      genome multiplications but rarely duplicate through small-scale duplication, a
      pattern referred to as reciprocal retention. This peculiar duplication behavior
      is hypothesized to stem from constraints on the dosage balance between the genes
      concerned and their interaction context. However, the evidence for a relationship
      between reciprocal retention and dosage balance sensitivity remains fragmentary.
      Here, we identified which gene families are most strongly reciprocally retained
      in the angiosperm lineage and studied their functional and evolutionary
      characteristics. Reciprocally retained gene families exhibit stronger sequence
      divergence constraints and lower rates of functional and expression divergence
      than other gene families, suggesting that dosage balance sensitivity is a general
      characteristic of reciprocally retained genes. Gene families functioning in
      regulatory and signaling processes are much more strongly represented at the top
      of the reciprocal retention ranking than those functioning in multiprotein
      complexes, suggesting that regulatory imbalances may lead to stronger fitness
      effects than classical stoichiometric protein complex imbalances. Finally,
      reciprocally retained duplicates are often subject to dosage balance constraints
      for prolonged evolutionary times, which may have repercussions for the ease with
      which genome multiplications can engender evolutionary innovation.

PMID- 29061874
TI  - Spineless solutions: The potential of invertebrate animal models for advancing
      science in the developing world.

PMID- 29061875
TI  - Dimple on the shoulder after a ski injury.
AB  - CLINICAL INTRODUCTION: A 74-year-old woman was brought to the ski clinic shortly
      after a fall on her left shoulder while skiing. She did not remember the exact
      fall mechanism. She felt a popping sensation in her left shoulder and was unable
      to move her left arm due to severe pain. Her medical and social histories were
      unremarkable. On physical examination, she had a deformity in her left shoulder
      (figure 1). Her neurovascular examination was
      intact.emermed;34/11/740/F1F1F1Figure 1Photograph of the left shoulder on arrival
      showing an anterior 'dimple'. QUESTION: What is the most likely diagnosis of the
      injury? An acromioclavicular joint (ACJ) sprain (shoulder separation)A proximal
      humerus fractureA distal clavicle fractureA posterior glenohumeral dislocation.

PMID- 29061876
TI  - BET 1: Does the use of emollients prevent frostbite to the face?
AB  - A short cut review was carried out to establish whether routine use of emollients
      on the face reduced the incidence of frostbite in cold environments. 126 papers
      were found using the reported searches, of which three presented the best
      evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these papers are tabulated. It is concluded that the use of
      emollients on the face is not a good protection against frostbite and may even
      result in a higher risk.

PMID- 29061878
TI  - BET 2: Should children with sport-related concussion observe strict physical rest
      until symptom-free?
AB  - A short cut review was carried out to establish whether strict physical rest
      following sports related concussion in children is better than normal activity in
      reducing post-concussional symptoms. two recent systematic reviews presented the
      best evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these papers are tabulated. It is concluded that children who
      present with a sport-related concussion should have a brief period of cognitive
      and physical rest followed by a gradual increase in activity. Further studies
      should examine the length of the brief rest period, however at this time 24-48
      hours of rest should be recommended.

PMID- 29061880
TI  - Correction: Exploring why 'primary care' problems end up receiving ambulance
      treatment: early findings from a pre-hospital ethnographic study.

PMID- 29061879
TI  - Correction: Investigating the population characteristics, processes and outcomes
      of pre-hospital psychiatric and self-harm emergencies in Scotland: a national
      record linkage study.

PMID- 29061884
TI  - The retromer, sorting nexins and the plant endomembrane protein trafficking.
AB  - Protein sorting in the endomembrane system is responsible for the coordination of
      cellular functions. Plant intracellular trafficking has its own unique features,
      which include specific regulatory aspects of endosomal sorting and recycling of
      cargo proteins, mediated by the retromer complex. Recent work has led to
      significant progress in understanding the role of Arabidopsis retromer subunits
      in recycling vacuolar sorting receptors and plasma membrane proteins. As a
      consequence, members of the sorting nexin (SNX) protein family and their
      interaction partners have emerged as critical protein trafficking regulators, in
      particular with regard to adaptation to environmental change, such as temperature
      fluctuations and nutrient deficiency. In this Review, we discuss the known and
      proposed functions of the comparatively small Arabidopsis SNX protein family. We
      review the available information on the role of the three Bin-Amphiphysin-Rvs
      (BAR)-domain-containing Arabidopsis thaliana (At)SNX proteins and discuss their
      function in the context of their potential participation in the plant retromer
      complex. We also summarize the role of AtSNX1-interacting proteins in different
      aspects of SNX-dependent protein trafficking and comment on the potential
      function of three novel, as yet unexplored, Arabidopsis SNX proteins.

PMID- 29061882
TI  - ADF10 shapes the overall organization of apical actin filaments by promoting
      their turnover and ordering in pollen tubes.
AB  - Here, we show that Arabidopsis ADF10 plays an important role in shaping the
      overall organization of apical actin filaments by promoting their turnover and
      ordering. ADF10 severs and depolymerizes actin filaments in vitro and is
      distributed throughout the entire pollen tube. In adf10 mutants, severing and
      monomer dissociation events for apical actin filaments are reduced, and the
      apical actin structure extends further toward the tube base than in wild-type
      tubes. In particular, the percentage of apical actin filaments that form large
      angles to the tube growth axis is much higher in adf10 pollen tubes, and the
      actin filaments are more randomly distributed, implying that ADF10 promotes their
      ordering. Consistent with the role of apical actin filaments in physically
      restricting the movement of vesicles, the region in which apical vesicles
      accumulate is enlarged at the tip of adf10 pollen tubes. Both tipward and
      backward movements of small vesicles are altered within the growth domain of
      adf10 pollen tubes. Thus, our study suggests that ADF10 shapes the organization
      of apical actin filaments to regulate vesicle trafficking and pollen tube growth.

PMID- 29061881
TI  - E-cadherin cleavage by MT2-MMP regulates apical junctional signaling and
      epithelial homeostasis in the intestine.
AB  - Cadherin-based intercellular adhesions are essential players in epithelial
      homeostasis, but their dynamic regulation during tissue morphogenesis and
      remodeling remain largely undefined. Here, we characterize an unexpected role for
      the membrane-anchored metalloproteinase MT2-MMP in regulating epithelial cell
      quiescence. Following co-immunoprecipitation and mass spectrometry, the MT2-MMP
      cytosolic tail was found to interact with the zonula occludens protein-1 (ZO-1)
      at the apical junctions of polarized epithelial cells. Functionally, MT2-MMP
      localizes in the apical domain of epithelial cells where it cleaves E-cadherin
      and promotes epithelial cell accumulation, a phenotype observed in 2D polarized
      cells as well as 3D cysts. MT2-MMP-mediated cleavage subsequently disrupts apical
      E-cadherin-mediated cell quiescence resulting in relaxed apical cortical tension
      favoring cell extrusion and re-sorting of Src kinase activity to junctional
      complexes, thereby promoting proliferation. Physiologically, MT2-MMP loss of
      function alters E-cadherin distribution, leading to impaired 3D organoid
      formation by mouse colonic epithelial cells ex vivo and reduction of cell
      proliferation within intestinal crypts in vivo Taken together, these studies
      identify an MT2-MMP-E-cadherin axis that functions as a novel regulator of
      epithelial cell homeostasis in vivo.

PMID- 29061885
TI  - Retraction: Suppression of intestinal tumorigenesis in Apc mutant mice upon
      Musashi-1 deletion. J. Cell Sci. doi: 10.1242/jcs.197574.

PMID- 29061883
TI  - KIF13A mediates trafficking of influenza A virus ribonucleoproteins.
AB  - Influenza A is a rapidly evolving virus that is successful in provoking periodic
      epidemics and occasional pandemics in humans. Viral assembly is complex as the
      virus incorporates an eight-partite genome of RNA (in the form of viral
      ribonucleoproteins, vRNPs), and viral genome assembly - with its implications to
      public health - is not completely understood. It has previously been reported
      that vRNPs are transported to the cell surface on Rab11-containing vesicles by
      using microtubules but, so far, no molecular motor has been assigned to the
      process. Here, we have identified KIF13A, a member of the kinesin-3 family, as
      the first molecular motor to efficiently transport vRNP-Rab11 vesicles during
      infection with influenza A. Depletion of KIF13A resulted in reduced viral titers
      and less accumulation of vRNPs at the cell surface, without interfering with the
      levels of other viral proteins at sites of viral assembly. In addition, when
      overexpressed and following two separate approaches to displace vRNP-Rab11
      vesicles, KIF13A increased levels of vRNP at the plasma membrane. Together, our
      results show that KIF13A plays an important role in the transport of influenza A
      vRNPs, a crucial step for viral assembly.This article has an associated First
      Person interview with the first author of the paper.

PMID- 29061886
TI  - Users' experiences of an online intervention for bipolar disorder: important
      lessons for design and evaluation.
AB  - BACKGROUND: The evidence base for digital interventions for physical and mental
      health, including severe and enduring mental health difficulties, is increasing.
      In a feasibility trial, web-based Enhanced Relapse Prevention (ERPonline) for
      bipolar disorder demonstrated high recruitment and retention rates. Relative to
      participants in the waitlist control group, those who received ERPonline showed
      increased monitoring for early warning signs of relapse and had developed more
      positive illness models. OBJECTIVE: To understand users' motivations and barriers
      for taking part in an online/telephone-based trial, and for engagement with
      ERPonline. METHODS: Participants from the trial who had been allocated to receive
      ERPonline were purposively sampled to participate in telephone-based, in-depth
      qualitative interviews about their experiences. Interviews (n=19) were analysed
      using framework analysis to identify themes relevant to study aims. FINDINGS:
      Participants took part due to the convenient, flexible and rewarding aspects of
      the trial design, as well as a desire to improve the mental health of themselves
      and others. Barriers included extensive assessments, practical difficulties and
      mood. ERPonline was was generally considered to be accessible, relevant and
      straightforward, but there were individual preferences regarding design, content
      and who it was for. Several participants reported positive changes, but there was
      a sense that digital interventions should not replace routine care. CONCLUSIONS:
      There are a number of barriers and facilitators to consider when evaluating and
      implementing digital interventions. Individual preferences and human contact were
      key factors for both trial design and engagement with an online intervention.
      CLINICAL IMPLICATIONS: Digital interventions should be co-produced, personalised,
      interactive and embedded as one component in a broader package of care. TRIAL
      REGISTRATION NUMBER: ISRCTN56908625; Post-results.

PMID- 29061888
TI  - Innovation and the growth of human population.
AB  - Biodiversity is sustained by and is essential to the services that ecosystems
      provide. Different species would use these services in different ways, or
      adaptive strategies, which are sustained in time by continuous innovations. Using
      this framework, we postulate a model for a biological species (Homo sapiens) in a
      finite world where innovations, aimed at increasing the flux of ecosystem
      services (a measure of habitat quality), increase with population size, and have
      positive effects on the generation of new innovations (positive feedback) as well
      as costs in terms of negatively affecting the provision of ecosystem services. We
      applied this model to human populations, where technological innovations are
      driven by cumulative cultural evolution. Our model shows that depending on the
      net impact of a technology on the provision of ecosystem services (theta), and
      the strength of technological feedback (xi), different regimes can result. Among
      them, the human population can fill the entire planet while maximizing their well
      being, but not exhaust ecosystem services. However, this outcome requires
      positive or green technologies that increase the provision of ecosystem services
      with few negative externalities or environmental costs, and that have a strong
      positive feedback in generating new technologies of the same kind. If the
      feedback is small, then the technological stock can collapse together with the
      human population. Scenarios where technological innovations generate net negative
      impacts may be associated with a limited technological stock as well as a limited
      human population at equilibrium and the potential for collapse. The only way to
      fill the planet with humans under this scenario of negative technologies is by
      reducing the technological stock to a minimum. Otherwise, the only feasible
      equilibrium is associated with population collapse. Our model points out that
      technological innovations per se may not help humans to grow and dominate the
      planet. Instead, different possibilities unfold for our future depending on their
      impact on the environment and on further innovation.This article is part of the
      themed issue 'Process and pattern in innovations from cells to societies'.

PMID- 29061889
TI  - Information theory, evolutionary innovations and evolvability.
AB  - How difficult is it to 'discover' an evolutionary adaptation or innovation? I
      here suggest that information theory, in combination with high-throughput DNA
      sequencing, can help answer this question by quantifying a new phenotype's
      information content. I apply this framework to compute the phenotypic information
      associated with novel gene regulation and with the ability to use novel carbon
      sources. The framework can also help quantify how DNA duplications affect
      evolvability, estimate the complexity of phenotypes and clarify the meaning of
      'progress' in Darwinian evolution.This article is part of the themed issue
      'Process and pattern in innovations from cells to societies'.

PMID- 29061887
TI  - Innovation: an emerging focus from cells to societies.
AB  - Innovations are generally unexpected, often spectacular changes in phenotypes and
      ecological functions. The contributions to this theme issue are the latest
      conceptual, theoretical and experimental developments, addressing how ecology,
      environment, ontogeny and evolution are central to understanding the complexity
      of the processes underlying innovations. Here, we set the stage by introducing
      and defining key terms relating to innovation and discuss their relevance to
      biological, cultural and technological change. Discovering how the generation and
      transmission of novel biological information, environmental interactions and
      selective evolutionary processes contribute to innovation as an ecosystem will
      shed light on how the dominant features across life come to be, generalize to
      social, cultural and technological evolution, and have applications in the health
      sciences and sustainability.This article is part of the theme issue 'Process and
      pattern in innovations from cells to societies'.

PMID- 29061891
TI  - The conceptual foundations of network-based diffusion analysis: choosing networks
      and interpreting results.
AB  - Network-based diffusion analysis (NBDA) is a statistical technique for detecting
      the social transmission of behavioural innovations in groups of animals,
      including humans. The strength of social transmission is inferred from the extent
      to which the diffusion (spread) of the innovation follows a social network. NBDA
      can have two goals: (a) to establish whether social transmission is occurring and
      how strong its effects are; and/or (b) to establish the typical pathways of
      information transfer. The technique has been used in a range of taxa, including
      primates, cetaceans, birds and fish, using a range of different types of network.
      Here I investigate the conceptual underpinnings of NBDA, in order to establish
      the meaning of results using different networks. I develop a model of the social
      transmission process where each individual observation of the target behaviour
      affects the rate at which the observer learns that behaviour. I then establish
      how NBDAs using different networks relate to this underlying process, and thus
      how we can interpret the results of each. My analysis shows that a different
      network or networks are appropriate depending on the specific goal or goals of
      the study, and establishes how the parameter estimates yielded from an NBDA can
      be interpreted for different networks.This article is part of the themed issue
      'Process and pattern in innovations from cells to societies'.

PMID- 29061890
TI  - Phylogenetic tests for evolutionary innovation: the problematic link between key
      innovations and exceptional diversification.
AB  - Evolutionary innovation contributes to the spectacular diversity of species and
      phenotypes across the tree of life. 'Key innovations' are widely operationalized
      within evolutionary biology as traits that facilitate increased diversification
      rates, such that lineages bearing the traits ultimately contain more species than
      closely related lineages lacking the focal trait. In this article, I briefly
      review the inference, analysis and interpretation of evolutionary innovation on
      phylogenetic trees. I argue that differential rates of lineage diversification
      should not be used as the basis for key innovation tests, despite the statistical
      tractability of such approaches. Under traditional interpretations of the
      macroevolutionary 'adaptive zone', we should not necessarily expect key
      innovations to confer faster diversification rates upon lineages that possess
      them relative to their extant sister clades. I suggest that a key innovation is a
      trait that allows a lineage to interact with the environment in a fundamentally
      different way and which, as a result, increases the total diversification-but not
      necessarily the diversification rate-of the parent clade. Considered alone,
      branching patterns in phylogenetic trees are poorly suited to the inference of
      evolutionary innovation due to their inherently low information content with
      respect to the processes that produce them. However, phylogenies may be important
      for identifying transformational shifts in ecological and morphological space
      that are characteristic of innovation at the macroevolutionary scale.This article
      is part of the themed issue 'Process and pattern in innovations from cells to
      societies'.

PMID- 29061892
TI  - The origin of heredity in protocells.
AB  - Here we develop a computational model that examines one of the first major
      biological innovations-the origin of heredity in simple protocells. The model
      assumes that the earliest protocells were autotrophic, producing organic matter
      from CO2 and H2 Carbon fixation was facilitated by geologically sustained proton
      gradients across fatty acid membranes, via iron-sulfur nanocrystals lodged within
      the membranes. Thermodynamic models suggest that organics formed this way should
      include amino acids and fatty acids. We assume that fatty acids partition to the
      membrane. Some hydrophobic amino acids chelate FeS nanocrystals, producing three
      positive feedbacks: (i) an increase in catalytic surface area; (ii) partitioning
      of FeS nanocrystals to the membrane; and (iii) a proton-motive active site for
      carbon fixing that mimics the enzyme Ech. These positive feedbacks enable the
      fastest-growing protocells to dominate the early ecosystem through a simple form
      of heredity. We propose that as new organics are produced inside the protocells,
      the localized high-energy environment is more likely to form ribonucleotides,
      linking RNA replication to its ability to drive protocell growth from the
      beginning. Our novel conceptualization sets out conditions under which protocell
      heredity and competition could arise, and points to where crucial experimental
      work is required.This article is part of the themed issue 'Process and pattern in
      innovations from cells to societies'.

PMID- 29061893
TI  - Nascent life cycles and the emergence of higher-level individuality.
AB  - Evolutionary transitions in individuality (ETIs) occur when formerly autonomous
      organisms evolve to become parts of a new, 'higher-level' organism. One of the
      first major hurdles that must be overcome during an ETI is the emergence of
      Darwinian evolvability in the higher-level entity (e.g. a multicellular group),
      and the loss of Darwinian autonomy in the lower-level units (e.g. individual
      cells). Here, we examine how simple higher-level life cycles are a key innovation
      during an ETI, allowing this transfer of fitness to occur 'for free'.
      Specifically, we show how novel life cycles can arise and lead to the origin of
      higher-level individuals by (i) mitigating conflicts between levels of selection,
      (ii) engendering the expression of heritable higher-level traits and (iii)
      allowing selection to efficiently act on these emergent higher-level traits.
      Further, we compute how canonical early life cycles vary in their ability to fix
      beneficial mutations via mathematical modelling. Life cycles that lack a
      persistent lower-level stage and develop clonally are far more likely to fix
      'ratcheting' mutations that limit evolutionary reversion to the pre-ETI state. By
      stabilizing the fragile first steps of an evolutionary transition in
      individuality, nascent higher-level life cycles may play a crucial role in the
      origin of complex life.This article is part of the themed issue 'Process and
      pattern in innovations from cells to societies'.

PMID- 29061894
TI  - Cooperation and cheating as innovation: insights from cellular societies.
AB  - The capacity to innovate is often considered a defining feature of human
      societies, but it is not a capacity that is unique to human societies: innovation
      occurs in cellular societies as well. Cellular societies such as multicellular
      bodies and microbial communities, including the human microbiome, are capable of
      innovation in response to novel opportunities and threats. Multicellularity
      represents a suite of innovations for cellular cooperation, but multicellularity
      also opened up novel opportunities for cells to cheat, exploiting the
      infrastructure and resources of the body. Multicellular bodies evolve less
      quickly than the cells within them, leaving them vulnerable to cellular
      innovations that can lead to cancer and infections. In order to counter these
      threats, multicellular bodies deploy additional innovations including the
      adaptive immune system and the development of partnerships with preferred
      microbial partners. What can we learn from examining these innovations in
      cooperation and cheating in cellular societies? First, innovation in social
      systems involves a constant tension between novel mechanisms that enable greater
      size and complexity of cooperative entities and novel ways of cheating. Second,
      cultivating cooperation with partners who can rapidly and effectively innovate
      (such as microbes) is important for large entities including multicellular
      bodies. And third, multicellularity enabled cells to manage risk socially,
      allowing organisms to survive in challenging environments where life would
      otherwise be impossible. Throughout, we ask how insights from cellular societies
      might be translated into new innovations in human health and medicine, promoting
      and protecting the cellular cooperation that makes us viable multicellular
      organisms.This article is part of the themed issue 'Process and pattern in
      innovations from cells to societies'.

PMID- 29061895
TI  - The topology of evolutionary novelty and innovation in macroevolution.
AB  - Sewall Wright's fitness landscape introduced the concept of evolutionary spaces
      in 1932. George Gaylord Simpson modified this to an adaptive, phenotypic
      landscape in 1944 and since then evolutionary spaces have played an important
      role in evolutionary theory through fitness and adaptive landscapes, phenotypic
      and functional trait spaces, morphospaces and related concepts. Although the
      topology of such spaces is highly variable, from locally Euclidean to pre
      topological, evolutionary change has often been interpreted as a search through a
      pre-existing space of possibilities, with novelty arising by accessing previously
      inaccessible or difficult to reach regions of a space. Here I discuss the nature
      of evolutionary novelty and innovation within the context of evolutionary spaces,
      and argue that the primacy of search as a conceptual metaphor ignores the
      generation of new spaces as well as other changes that have played important
      evolutionary roles.This article is part of the themed issue 'Process and pattern
      in innovations from cells to societies'.

PMID- 29061897
TI  - Innovation and social transmission in experimental micro-societies: exploring the
      scope of cumulative culture in young children.
AB  - The experimental study of cumulative culture and the innovations essential to it
      is a young science, with child studies so rare that the scope of cumulative
      cultural capacities in childhood remains largely unknown. Here we report a new
      experimental approach to the inherent complexity of these phenomena. Groups of 3
      4-year-old children were presented with an elaborate array of challenges
      affording the potential cumulative development of a variety of techniques to gain
      increasingly attractive rewards. In contrast to a prior study, we found evidence
      for elementary forms of cumulative cultural progress, with inventions of
      solutions at lower levels spreading to become shared innovations, and some
      children then building on these to create more advanced but more rewarding
      innovations. This contrasted with markedly more constrained progress when
      children worked only by themselves, or if groups faced only the highest-level
      challenges from the start. Further experiments that introduced higher-level
      inventions via the inclusion of older children, or that created ecological
      change, with the easiest habitual solutions no longer possible, encouraged higher
      levels of cumulative innovation. Our results show children are not merely
      'cultural sponges', but when acting in groups, display the beginnings of cycles
      of innovation and observational learning that sustain cumulative progress in
      problem solving.This article is part of the themed issue 'Process and pattern in
      innovations from cells to societies'.

PMID- 29061898
TI  - Inferring processes of cultural transmission: the critical role of rare variants
      in distinguishing neutrality from novelty biases.
AB  - Neutral evolution assumes that there are no selective forces distinguishing
      different variants in a population. Despite this striking assumption, many recent
      studies have sought to assess whether neutrality can provide a good description
      of different episodes of cultural change. One approach has been to test whether
      neutral predictions are consistent with observed progeny distributions, recording
      the number of variants that have produced a given number of new instances within
      a specified time interval: a classic example is the distribution of baby names.
      Using an overlapping generations model, we show that these distributions consist
      of two phases: a power-law phase with a constant exponent of [Formula: see text],
      followed by an exponential cut-off for variants with very large numbers of
      progeny. Maximum-likelihood estimations of the model parameters provide a direct
      way to establish whether observed empirical patterns are consistent with neutral
      evolution. We apply our approach to a complete dataset of baby names from
      Australia. Crucially, we show that analyses based on only the most popular
      variants, as is often the case in studies of cultural evolution, can provide
      misleading evidence for underlying transmission hypotheses. While neutrality
      provides a plausible description of progeny distributions of abundant variants,
      rare variants deviate from neutrality. Further, we develop a simulation framework
      that allows the detection of alternative cultural transmission processes. We show
      that anti-novelty bias is able to replicate the complete progeny distribution of
      the Australian dataset.This article is part of the themed issue 'Process and
      pattern in innovations from cells to societies'.

PMID- 29061896
TI  - Sampling the mobile gene pool: innovation via horizontal gene transfer in
      bacteria.
AB  - In biological systems, evolutionary innovations can spread not only from parent
      to offspring (i.e. vertical transmission), but also 'horizontally' between
      individuals, who may or may not be related. Nowhere is this more apparent than in
      bacteria, where novel ecological traits can spread rapidly within and between
      species through horizontal gene transfer (HGT). This important evolutionary
      process is predominantly a by-product of the infectious spread of mobile genetic
      elements (MGEs). We will discuss the ecological conditions that favour the spread
      of traits by HGT, the evolutionary and social consequences of sharing traits, and
      how HGT is shaped by inherent conflicts between bacteria and MGEs.This article is
      part of the themed issue 'Process and pattern in innovations from cells to
      societies'.

PMID- 29061899
TI  - Cognitive innovations and the evolutionary biology of expertise.
AB  - Animal life can be perceived as the selective use of information for maximizing
      survival and reproduction. All organisms including bacteria and protists rely on
      genetic networks to build and modulate sophisticated structures and biochemical
      mechanisms for perceiving information and responding to environmental changes.
      Animals, however, have gone through a series of innovations that dramatically
      increased their capacity to acquire, retain and act upon information.
      Multicellularity was associated with the evolution of the nervous system, which
      took over many tasks of internal communication and coordination. This paved the
      way for the evolution of learning, initially based on individual experience and
      later also via social interactions. The increased importance of social learning
      also led to the evolution of language in a single lineage. Individuals' ability
      to dramatically increase performance via learning may have led to an evolutionary
      cycle of increased lifespan and greater investment in cognitive abilities, as
      well as in the time necessary for the development and refinement of expertise. We
      still know little, however, about the evolutionary biology, genetics and
      neurobiological mechanisms that underlie such expertise and its development.This
      article is part of the themed issue 'Process and pattern in innovations from
      cells to societies'.

PMID- 29061900
TI  - The niche construction of cultural complexity: interactions between innovations,
      population size and the environment.
AB  - Niche construction is a process through which organisms alter their environments
      and, in doing so, influence or change the selective pressures to which they are
      subject. 'Cultural niche construction' refers specifically to the effect of
      cultural traits on the selective environments of other biological or cultural
      traits and may be especially important in human evolution. In addition, the
      relationship between population size and cultural accumulation has been the
      subject of extensive debate, in part because anthropological studies have
      demonstrated a significant association between population size and toolkit
      complexity in only a subset of studied cultures. Here, we review the role of
      cultural innovation in constructing human evolutionary niches and introduce a new
      model to describe the accumulation of human cultural traits that incorporates the
      effects of cultural niche construction. We consider the results of this model in
      light of available data on human toolkit sizes across populations to help
      elucidate the important differences between food-gathering societies and food
      producing societies, in which niche construction may be a more potent force.
      These results support the idea that a population's relationship with its
      environment, represented here by cultural niche construction, should be
      considered alongside population size in studies of cultural complexity.This
      article is part of the themed issue 'Process and pattern in innovations from
      cells to societies'.

PMID- 29061901
TI  - Geographic mosaics and changing rates of cereal domestication.
AB  - Domestication is the process by which plants or animals evolved to fit a human
      managed environment, and it is marked by innovations in plant morphology and
      anatomy that are in turn correlated with new human behaviours and technologies
      for harvesting, storage and field preparation. Archaeobotanical evidence has
      revealed that domestication was a protracted process taking thousands of plant
      generations. Within this protracted process there were changes in the selection
      pressures for domestication traits as well as variation across a geographic
      mosaic of wild and cultivated populations. Quantitative data allow us to estimate
      the changing selection coefficients for the evolution of non-shattering (domestic
      type seed dispersal) in Asian rice (Oryza sativa L.), barley (Hordeum vulgare
      L.), emmer wheat (Triticum dicoccon (Shrank) Schubl.) and einkorn wheat (Triticum
      monococcum L.). These data indicate that selection coefficients tended to be low,
      but also that there were inflection points at which selection increased
      considerably. For rice, selection coefficients of the order of 0.001 prior to
      5500 BC shifted to greater than 0.003 between 5000 and 4500 BC, before falling
      again as the domestication process ended 4000-3500 BC. In barley and the two
      wheats selection was strongest between 8500 and 7500 BC. The slow start of
      domestication may indicate that initial selection began in the Pleistocene
      glacial era.This article is part of the themed issue 'Process and pattern in
      innovations from cells to societies'.

PMID- 29061902
TI  - Non-adaptive origins of evolutionary innovations increase network complexity in
      interacting digital organisms.
AB  - The origin of evolutionary innovations is a central problem in evolutionary
      biology. To what extent such innovations have adaptive or non-adaptive origins is
      hard to assess in real organisms. This limitation, however, can be overcome using
      digital organisms, i.e. self-replicating computer programs that mutate, evolve
      and coevolve within a user-defined computational environment. Here, we quantify
      the role of the non-adaptive origins of host resistance traits in determining the
      evolution of ecological interactions among host and parasite digital organisms.
      We find that host resistance traits arising spontaneously as exaptations increase
      the complexity of antagonistic host-parasite networks. Specifically, they lead to
      higher host phenotypic diversification, a larger number of ecological
      interactions and higher heterogeneity in interaction strengths. Given the
      potential of network architecture to affect network dynamics, such exaptations
      may increase the persistence of entire communities. Our in silico approach,
      therefore, may complement current theoretical advances aimed at disentangling the
      ecological and evolutionary mechanisms shaping species interaction networks.This
      article is part of the themed issue 'Process and pattern in innovations from
      cells to societies'.

PMID- 29061904
TI  - Chlorophyll Can Be Reduced in Crop Canopies with Little Penalty to
      Photosynthesis.
AB  - The hypothesis that reducing chlorophyll content (Chl) can increase canopy
      photosynthesis in soybeans was tested using an advanced model of canopy
      photosynthesis. The relationship among leaf Chl, leaf optical properties, and
      photosynthetic biochemical capacity was measured in 67 soybean (Glycine max)
      accessions showing large variation in leaf Chl. These relationships were
      integrated into a biophysical model of canopy-scale photosynthesis to simulate
      the intercanopy light environment and carbon assimilation capacity of canopies
      with wild type, a Chl-deficient mutant (Y11y11), and 67 other mutants spanning
      the extremes of Chl to quantify the impact of variation in leaf-level Chl on
      canopy-scale photosynthetic assimilation and identify possible opportunities for
      improving canopy photosynthesis through Chl reduction. These simulations
      demonstrate that canopy photosynthesis should not increase with Chl reduction due
      to increases in leaf reflectance and nonoptimal distribution of canopy nitrogen.
      However, similar rates of canopy photosynthesis can be maintained with a 9%
      savings in leaf nitrogen resulting from decreased Chl. Additionally, analysis of
      these simulations indicate that the inability of Chl reductions to increase
      photosynthesis arises primarily from the connection between Chl and leaf
      reflectance and secondarily from the mismatch between the vertical distribution
      of leaf nitrogen and the light absorption profile. These simulations suggest that
      future work should explore the possibility of using reduced Chl to improve canopy
      performance by adapting the distribution of the "saved" nitrogen within the
      canopy to take greater advantage of the more deeply penetrating light.

PMID- 29061905
TI  - Revisiting the Algal "Chloroplast Lipid Droplet": The Absence of an Entity That
      Is Unlikely to Exist.
AB  - The precise localization of the lipid droplets and the metabolic pathways
      associated with oil production are crucial to the engineering of microalgae for
      biofuel production. Several studies have reported detecting lipid droplets within
      the chloroplast of the microalga Chlamydomonas reinhardtii, which accumulates
      considerable amounts of triacylglycerol and starch within the cell under nitrogen
      deprivation or high-light stress conditions. Starch undoubtedly accumulates
      within the chloroplast, but there have been debates on the localization of the
      lipid droplets, which are cytosolic organelles in other organisms. Although it is
      impossible to prove an absence, we tried to repeat experiments that previously
      indicated the presence of lipid droplets in chloroplasts. Here, we present
      microscopic results showing no evidence for the presence of lipid droplets within
      the chloroplast stroma, even though some lipid droplets existed in close
      association with the chloroplast or were largely engulfed by the chloroplasts.
      These lipid droplets are cytosolic structures, distinct from the plastoglobules
      present in the chloroplast stroma. These results not only contrast with the old
      ideas but also point out that what were previously thought to be chloroplast
      lipid droplets are likely to be embedded within chloroplast invaginations in
      association with the outer envelope of the chloroplast without intervention of
      the endoplasmic reticulum. These findings point to the intriguing possibility of
      a tight metabolic flow from the chloroplast to the lipid droplet through a close
      association rather than direct contact of both organelles.

PMID- 29061903
TI  - Dynamics of Autophagosome Formation.

PMID- 29061906
TI  - ABA Accumulation in Dehydrating Leaves Is Associated with Decline in Cell Volume,
      Not Turgor Pressure.

PMID- 29061909
TI  - Dose-time response association between occupational asbestos exposure and pleural
      mesothelioma: authors' response.

PMID- 29061907
TI  - Deubiquitinating Enzyme OTU5 Contributes to DNA Methylation Patterns and Is
      Critical for Phosphate Nutrition Signals.
AB  - Phosphate (Pi) starvation induces a suite of adaptive responses aimed at
      recalibrating cellular Pi homeostasis. Plants harboring a mutation in OVARIAN
      TUMOR DOMAIN-CONTAINING DEUBIQUITINATING ENZYME5 (OTU5) showed altered DNA
      methylation of root hair-related genes and altered Pi-responsive root traits.
      Unlike the wild type, homozygous otu5 mutants did not respond to Pi starvation by
      increased lateral root formation and increased root hair length but formed very
      short root hairs when grown on low-Pi media. Under Pi-replete conditions, otu5
      plants developed more root hairs than the wild type due to attenuated primary
      root growth, a phenotype that resembled that of Pi-deficient plants. Growth of
      plants on low-Pi media altered both H3K4 and H3K27 trimethylation levels at the
      transcriptional start site of a subset of genes encoding key players in Pi
      homeostasis, which was correlated with mRNA abundance changes of these genes. Pi
      starvation had a minor impact on DNA methylation. Differentially methylated
      regions were enriched in transposable elements, suggesting that DNA methylation
      associated with low Pi supply is required for maintaining genome integrity. It is
      concluded that DNA methylation and histone methylation constitute critical,
      interdependent regulatory components that orchestrate the activity of a subset of
      Pi-responsive genes.

PMID- 29061908
TI  - The RNA Editing Factor SlORRM4 Is Required for Normal Fruit Ripening in Tomato.
AB  - RNA editing plays a key posttranscriptional role in gene expression. Existing
      studies on cytidine-to-uridine RNA editing in plants have focused on maize (Zea
      mays), rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana). However, the
      importance and regulation of RNA editing in several critical agronomic processes
      are not well understood, a notable example of which is fruit ripening. Here, we
      analyzed the expression profile of 33 RNA editing factors and identified 11
      putative tomato (Solanum lycopersicum) fruit ripening-related factors. A rapid
      virus-induced gene silencing assay indicated that the organelle RNA recognition
      motif-containing protein SlORRM4 affected tomato fruit ripening. Knocking out
      SlORRM4 expression using a clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated protein 9 genome editing strategy delayed
      tomato fruit ripening by lowering respiratory rate and ethylene production.
      Additionally, the expression of numerous genes associated with fruit ripening and
      mitochondrial functions changed significantly when SlORRM4 was knocked out.
      Moreover, the loss of SlORRM4 function significantly reduced RNA editing of many
      mitochondrial transcripts, leading to low-level expression of some core subunits
      that are critical for mitochondrial complex assembly (i.e. Nad3, Cytc1, and COX
      II). Taken together, these results indicate that SlORRM4 is involved in RNA
      editing of transcripts in ripening fruit that influence mitochondrial function
      and key aspects of fruit ripening.

PMID- 29061910
TI  - Health Coaching in Severe COPD After a Hospitalization: A Qualitative Analysis of
      a Large Randomized Study.
AB  - BACKGROUND: We recently demonstrated in a randomized study the feasibility and
      effectiveness of telephone-based health coaching using motivational interviewing
      on decreasing hospital readmissions and improving quality of life at 6 and 12
      months after hospital discharge. In this qualitative study, we sought to explore
      the health-coaching intervention as seen from the perspective of the participants
      who received the intervention and the coaches who delivered it. METHODS:
      Semistructured participant interviews (n = 24) and a focus group of all health
      coaches (n = 3) who participated in this study were conducted. Interviews and
      focus group were recorded and transcribed verbatim. Transcripts were analyzed
      using coding and categorizing techniques and thematic analysis. Mixed-method
      triangulation was used to merge quantitative and qualitative data. RESULTS:
      Content analysis revealed 4 predominant themes of the coaching intervention:
      health-coaching relationship, higher participant confidence and reassurance (most
      related to improvement in physical quality of life), improved health-care system
      access (most related to decreased hospital readmissions), and increased awareness
      of COPD symptoms (most related to improvement in emotional quality of life). The
      strongest theme was the relationship with the health coach, including coach style
      and motivational interviewing approach. Health coaches' focus group also noted
      the importance of the coaching relationship as the most significant theme.
      CONCLUSIONS: This study provided themes to further inform the delivery and
      implementation of health-coaching interventions in patients with COPD after
      hospital discharge. Health coaching forged partnerships and created a platform
      for patient engagement, which was confirmed by both participants and health
      coaches.

PMID- 29061911
TI  - Ventilator-Associated Events 5 Years Later.

PMID- 29061912
TI  - The Ongoing Question of Where Clinicians Should Place the Nebulizer in the
      Ventilator Circuit: This Time With Epoprostenol.

PMID- 29061914
TI  - Therapeutics targeting Bcl-2 in hematological malignancies.
AB  - Members of the B-cell lymphoma 2 (BCL-2) gene family are attractive targets for
      cancer therapy as they play a key role in promoting cell survival, a long-since
      established hallmark of cancer. Clinical utility for selective inhibition of
      specific anti-apoptotic Bcl-2 family proteins has recently been realized with the
      Food and Drug Administration (FDA) approval of venetoclax (formerly ABT-199/GDC
      0199) in relapsed chronic lymphocytic leukemia (CLL) with 17p deletion. Despite
      the impressive monotherapy activity in CLL, such responses have rarely been
      observed in other B-cell malignancies, and preclinical data suggest that
      combination therapies will be needed in other indications. Additional selective
      antagonists of Bcl-2 family members, including Bcl-XL and Mcl-1, are in various
      stages of preclinical and clinical development and hold the promise of extending
      clinical utility beyond CLL and overcoming resistance to venetoclax. In addition
      to direct targeting of Bcl-2 family proteins with BH3 mimetics, combination
      therapies that aim at down-regulating expression of anti-apoptotic BCL-2 family
      members or restoring expression of pro-apoptotic BH3 family proteins may provide
      a means to deepen responses to venetoclax and extend the utility to additional
      indications. Here, we review recent progress in direct and selective targeting of
      Bcl-2 family proteins for cancer therapy and the search for rationale
      combinations.

PMID- 29061916
TI  - Stable ultra-thin CdTe crystal: a robust direct gap semiconductor.
AB  - Employing density functional theory based calculations, we investigate
      structural, vibrational and strain-dependent electronic properties of an ultra
      thin CdTe crystal structure that can be derived from its bulk counterpart. It is
      found that this ultra-thin crystal has an 8-atom primitive unit cell with
      considerable surface reconstructions. Dynamic stability of the structure is
      predicted based on its calculated vibrational spectrum. Electronic band structure
      calculations reveal that both electrons and holes in single layer CdTe possess
      anisotropic in-plane masses and mobilities. Moreover, we show that the ultra-thin
      CdTe has some interesting electromechanical features, such as strain-dependent
      anisotropic variation of the band gap value, and its rapid increase under
      perpendicular compression. The direct band gap semiconducting nature of the ultra
      thin CdTe crystal remains unchanged under all types of applied strain. With a
      robust and moderate direct band gap, single-layer CdTe is a promising material
      for nanoscale strain dependent device applications.

PMID- 29061915
TI  - The role and mechanism of action of sperm PLC-zeta in mammalian fertilisation.
AB  - At mammalian fertilisation, the fundamental stimulus that triggers oocyte (egg)
      activation and initiation of early embryonic development is an acute rise of the
      intracellular-free calcium (Ca2+) concentration inside the egg cytoplasm. This
      essential Ca2+ increase comprises a characteristic series of repetitive Ca2+
      oscillations, starting soon after sperm-egg fusion. Over the last 15 years,
      accumulating scientific and clinical evidence supports the notion that the
      physiological stimulus that precedes the cytosolic Ca2+ oscillations is a novel,
      testis-specific phospholipase C (PLC) isoform, known as PLC-zeta (PLCzeta). Sperm
      PLCzeta catalyses the hydrolysis of phosphatidylinositol 4,5-bisphosphate
      triggering cytosolic Ca2+ oscillations through the inositol 1,4,5-trisphosphate
      signalling pathway. PLCzeta is the smallest known mammalian PLC isoform with the
      most elementary domain organisation. However, relative to somatic PLCs, the
      PLCzeta isoform possesses a unique potency in stimulating Ca2+ oscillations in
      eggs that is attributed to its novel biochemical characteristics. In this review,
      we discuss the latest developments that have begun to unravel the vital role of
      PLCzeta at mammalian fertilisation and decipher its unique mechanism of action
      within the fertilising egg. We also postulate the significant potential
      diagnostic and therapeutic capacity of PLCzeta in alleviating certain types of
      male infertility.

PMID- 29061917
TI  - Production and mechanical properties of Ti-5Al-2.5Fe-xCu alloys for biomedical
      applications.
AB  - In this study, the mechanical, antibacterial properties and cell toxicity
      response of Ti-5Al2.5Fe alloy with different copper contents were investigated.
      The alloys were prepared by high-energy ball milling using elemental Ti, Al, Fe,
      and Cu powders and consolidated by a uniaxial vacuum hot press. Staphylococcus
      aureus strain ATCC 29213 and Escherichia coli strain ATCC 25922 were used to
      determine the antibacterial properties of the sintered alloys. The in vitro
      cytotoxicity of the samples was evaluated with HeLa (ATTC, CCL-2) cells using
      thiazolyl blue tetrazolium bromide. The mechanical behavior of the samples was
      determined as a function of hardness and bending tests and analyzed by scanning
      electron microscopy, energy dispersive x-ray spectroscopy, optical microscopy and
      x-ray diffraction (XRD). The results showed that the Cu content significantly
      improved the antibacterial properties. Cu addition prevented the formation of E.
      coli and S. aureus colonies on the surface of the samples. All samples exhibited
      very good cell biocompatibility. The alloys with different copper contents showed
      different mechanical properties, and the results were correlated by
      microstructural and XRD analyses in detail. Our results showed that Cu has a
      great effect on the Ti5Al2.5Fe alloy and the alloy is suitable for biomedical
      applications with enhanced antibacterial activity.

PMID- 29061918
TI  - Controlling the Vertical Dimension.

PMID- 29061919
TI  - Interdisciplinary Aligner Treatment of Short-Face Patients.

PMID- 29061921
TI  - Effects of Declining Battery Voltage on Light Intensity and Power Consumption of
      Light-Curing.

PMID- 29061920
TI  - Use of Osseointegrated Implants for Orthodontic Anchorage.

PMID- 29061922
TI  - Class II Correction in an Adult High-Angle Patient Using Low-Friction Mechanics
      and Skeletal Anchorage.

PMID- 29061923
TI  - Root-First Lingual Canine Retraction with Power Arms.

PMID- 29061924
TI  - Prevalence of Presenting Conditions in Grey Seal Pups (Halichoerus grypus)
      Admitted for Rehabilitation.
AB  - A retrospective survey was performed on the presenting conditions of 205 live
      grey seal pups (Halichoerus grypus) admitted to the Cornish Seal Sanctuary in
      Gweek, United Kingdom between May 2005 and March 2011. The purpose of the survey
      was to examine the prevalence of various presenting signs at the sanctuary. The
      presenting signs were classified into nine non-mutually exclusive categories:
      ocular disorders, nasal disorders, oral disorders, respiratory disorders,
      orthopaedic disorders, puncture wounds, abrasions, netting injuries, and onychia.
      The sex ratio of seal pups in this study was 1.35 males per female. Of the 205
      examined for rehabilitation, 22 (10.73%) did not survive to release. 68.78% of
      grey seal pups presented with puncture wounds, 47.80% with respiratory disorders,
      46.34% with ocular disorders, 42.63% malnourished, 36.59% with abrasions, 25.37%
      with oral disorders, 23.90% with nasal disorders, 11.71% with orthopaedic
      disorders, 9.27% with onychia, and 3.41% presented with netting injuries. 52%
      were normothermic, 42% were hyperthermic, and 5% were hypothermic. Associations
      between gender, outcome of rehabilitation, hospitalisation time and presenting
      disorders were examined. In addition, admissions rates were found to display
      seasonality. The results of this study will aid in future preparation of grey
      seal rehabilitation facilities.

PMID- 29061926
TI  - Medical Management of Cyclosporine-Induced Gingival Overgrowth Using Oral
      Azithromycin in Six Dogs.
AB  - Gingival overgrowth is an uncommon adverse effect of cyclosporine administration
      in veterinary species. In people, gingival overgrowth is a common complication of
      cyclosporine administration for immunosuppression, generally following transplant
      procedures. Azithromycin has been used successfully for managing gingival
      overgrowth in human transplant patients when cyclosporine administration cannot
      be reduced or discontinued. This case series describes six dogs being
      administered cyclosporine for various dermatologic diseases that developed
      gingival overgrowth. The dogs were prescribed systemic azithromycin, with or
      without concurrent dose reduction of cyclosporine. Oral administration of 6.6
      10.8 mg/kg of azithromycin once daily for 4-14 weeks was effective for complete
      clinical resolution of gingival overgrowth. In most cases, gingival overgrowth
      did not recur even with continued cyclosporine administration long-term. Adverse
      events of long-term azithromycin administration did not occur in any of the dogs.
      This series highlights a potentially beneficial medical treatment option for
      gingival overgrowth even when cyclosporine dose reduction is not possible or
      elected, without the need for surgical resection of proliferative gingival
      tissue.

PMID- 29061927
TI  - A Physician's View of One Health: Challenges and Opportunities.
AB  - One Health is one of the most important movements and emerging concepts in health
      today. The convergence of the fields of human and animal medicine has the
      potential to generate novel scientific hypotheses, create effective new therapies
      and potentially transform how physicians, veterinarians and their patients
      understand health and disease. Despite this potential, One Health has not yet
      gained significant awareness or traction in human medical communities. From its
      inception, One Health, sometimes also called One Medicine, has been piloted
      primarily by leaders from the world of veterinary medicine. Although the specific
      term was coined perhaps 10 years ago, comparative medicine has been quietly
      evident on university campuses with veterinary and medical schools for decades
      longer. Although a few physicians have played major leadership roles in One
      Health, in the United States, despite over ten years of the movement's robust
      growth, many have still not heard of it. Furthermore, physicians with some
      awareness of One Health often believe it to be primarily and exclusively about
      zoonotic infections and global health. The much broader scope and potential of
      One Health as also including comparative physiology and medicine is not being
      communicated effectively. Consequently, the human medical community remains
      largely disengaged. This is problematic because without significant engagement
      from physicians, nurses and other human health care professionals, the potential
      of One Health cannot be realized. To advance One Health it is imperative that we
      first understand the roots of under-engagement of the human medical community.
      This, in turn, can guide the development of novel and engaging opportunities for
      physician which demonstrate the power relevance of One Health's comparative,
      collaborative and cooperative approach.[...].

PMID- 29061928
TI  - Optimizing the Measurement of Colostrum Antibody Concentrations for Identifying
      BVDV Persistently Infected Calves.
AB  - Colostrum contains substantially higher concentrations of immunoglobulins
      compared to serum, which may help to improve the utility of diagnostic tests. The
      aim of this study was to determine the diagnostic value of colostrum antibody
      concentrations in identifying Bovine Viral Diarrhoea Virus (BVDV) PI
      (persistently infected) calf carrying beef heifers following an experimental
      infection. Colostrum was collected within 12 hours of parturition and tested in
      undiluted, 1:5, 1:10, 1:100, 1:200, and 1:500 dilutions using an enzyme-linked
      immunosorbent assay (ELISA) for BVDV antibody. Cows were determined to be
      carrying a PI calf based on positive quantitative Real Time-Polymerase Chain
      Reaction and antigen ELISA result on pre-colostral serum and ear notch samples
      collected from their calf. The median ELISA sample-to-positive (S/P) ratio for
      colostrum collected from heifers that carried a PI calf were significantly higher
      than the median ELISA S/P ratio for colostrum collected from heifers that did not
      carry a PI calf at dilutions of 1:100, 1:200, and 1:500. This study provides
      further evidence for increased antigenic stimulation in utero by the BVDV
      viraemic PI calf, which can also be identified with 100% diagnostic sensitivity
      when using 1:500 dilution colostrum.

PMID- 29061929
TI  - Development and Evaluation of a Novel Taqman Real-Time PCR Assay for Rapid
      Detection of Mycoplasma bovis: Comparison of Assay Performance with a
      Conventional PCR Assay and Another Taqman Real-Time PCR Assay.
AB  - The objective of this study was to develop and validate a Taqman real-time PCR
      assay for the detection of Mycoplasma bovis (M. bovis). Unique primers targeting
      the highly conserved house-keeping gene (uvrC) were designed and the probe
      sequence was derived from a previously published microarray study. There was 100%
      agreement in the outcome between our assay and the other two published assays for
      M. bovis detection. The analytical limit of detection of our assay is 83 copies
      of the uvrC gene. This assay was validated on a total of 214 bovine clinical
      specimens that were submitted to the Texas A&M Veterinary Medical Diagnostic
      Laboratory (TVMDL), Texas, USA. The specificity of the assay was assessed to be
      100% since no cross-reactivity occurred with 22 other bacterial and other
      Mycoplasma species. We conclude that the uvrC gene serves as a good and reliable
      diagnostic marker for the accurate and rapid detection of M. bovis from a wider
      variety of specimen matrices.

PMID- 29061930
TI  - Stimulation with Concanavalin-A Induces IL-17 Production by Canine Peripheral T
      Cells.
AB  - The characteristics of canine IL-17-producing cells are incompletely understood.
      Expression of mRNA encoding orthologs of IL-17 and the IL-17 receptor has been
      documented in tissues from dogs with arthritis, inflammatory bowel disease, and
      lymphoma; however, no associations have been found between IL-17 gene expression
      and disease phenotype in these conditions. Robust assessment of the role of IL-17
      producing cells in dogs will require measuring the frequency of these cells in
      health and disease in balance with other lymphocyte subsets. The aim of this
      study was to confirm that the T-cell IL-17 response in dogs is evolutionarily
      conserved. Canine peripheral blood mononuclear cells were stimulated with
      Concanavalin A with or without polarizing cytokines. We used a canine specific IL
      17 ELISA and flow cytometry to identify IL-17-producing T cells. Accumulation of
      intracellular IL-17 was observed in stimulated CD4 and CD8 T cells. The addition
      of pro-inflammatory cytokines appeared to enhance polarization of canine CD4 T
      cells to the Th17 phenotype. Conversely, the addition of IL-2 in the presence of
      TGF-beta resulted in expansion of Treg cells. We conclude that canine IL-17
      producing cells behave similarly to those from humans and mice when stimulated
      with mitogens and polarized with pro-inflammatory or immune regulatory cytokines.

PMID- 29061931
TI  - Alkylation and Carbamylation Effects of Lomustine and Its Major Metabolites and
      MGMT Expression in Canine Cells.
AB  - DNA Alkylation is thought to be the reason for the efficacy of lomustine while
      carbamylation has been implicated as the cause for the side effects seen with
      lomustine treatment such as hepatotoxicity. In the alkylation study we show that
      lomustine and its metabolites form similar levels of the DNA adducts N7
      hydroxyethylguanine and O6 hydroxyethyldeoxyguanosine. In terms of carbamylation,
      lomustine showed greater extent of carbamylation in the canine hepatocytes and
      lymphoma cell lines. The DNA repair enzyme O6 methylguanine DNA methyltransferase
      (MGMT) causes resistance of tumor cells to bifunctional nitrosourea, like
      lomustine. There is no data available regarding MGMT expression/activity in
      canine cells or tissues. Our study shows that there is low MGMT activity in the
      canine lymphoid cell line 17-71 while the GL-1 cells did not show any detectable
      enzyme activity or mRNA expression. The MGMT enzyme activity measured in canine
      hepatocytes is about 250-350 fmol/mg protein as compared to about 90 fmol/mg
      protein in 17-71 cells. We also show that MGMT mRNA expression in 17-71 cells and
      canine hepatocytes positively correlates with its enzyme activity in these cells.

PMID- 29061932
TI  - Governance and One Health: Exploring the Impact of Federalism and Bureaucracy on
      Zoonotic Disease Detection and Reporting.
AB  - The merits of One Health have been thoroughly described in the literature, but
      how One Health operates in the United States federal system of government is
      rarely discussed or analyzed. Through a comparative case-study approach, this
      research explores how federalism, bureaucratic behavior, and institutional design
      in the United States may influence zoonotic disease outbreak detection and
      reporting, a key One Health activity. Using theoretical and empirical literature,
      as well as a survey/interview instrument for individuals directly involved in a
      past zoonotic disease outbreak, the impacts of governance are discussed. As
      predicted in the theoretical literature, empirical findings suggest that
      federalism, institutional design, and bureaucracy may play a role in facilitating
      or impeding zoonotic disease outbreak detection and reporting. Regulatory
      differences across states as well as compartmentalization of information within
      agencies may impede disease detection. However, the impact may not always be
      negative: bureaucracies can also be adaptive; federalism allows states important
      opportunities for innovation. While acknowledging there are many other factors
      that also matter in zoonotic disease detection and reporting, this research is
      one of the first attempts to raise awareness in the literature and stimulate
      discussion on the intersection of governance and One Health.

PMID- 29061933
TI  - Intranuclear Inclusions in Renal Tubular Epithelium in Immunodeficient Mice Stain
      with Antibodies for Bovine Papillomavirus Type 1 L1 Protein.
AB  - The kidneys from six immunodeficient mice examined by Cerberus Sciences and the
      Animal Resources Centre, displayed karyomegaly with pale eosinophilic,
      intranuclear inclusions upon histopathological examination. Electron microscopy
      performed on kidney tissue from 5/6 mice demonstrated margination of the
      chromatin in large nuclei. Laboratory tests were used to detect nucleic acid of
      papillomaviruses, polyomaviruses, circoviruses and anelloviruses (4/6 mice), a
      specific PCR was used to detect murine polyomavirus (1/6), and a panel of
      serological tests was used to detect seroconversion to major murine pathogens
      (1/6). All molecular and serological tests were negative. Immunohistochemistry
      using polyclonal anti-bovine papillomavirus type 1 (BPV-1) L1 antibody, Camvir
      monoclonal anti-papillomavirus antibody (directed against the seven amino acids
      GFGAMDF found in human papillomavirus (HPV) 16 L1 protein), a commercially
      available mixture of two monoclonal antibodies, anti-BPV-1 L1/1H8 + Camvir
      antibodies, and a monoclonal anti-Hsc70 antibody revealed specific, positive
      staining of murine renal tubular epithelial intranuclear inclusions in 6/6 mice
      using the anti-BPV-1 L1 containing antibodies only. Methyl pyronin green, PAS and
      Feulgen histochemical reactions revealed that the intranuclear inclusions did not
      consist of RNA, DNA or carbohydrate. An immunohistochemical method now exists
      that can be used to confirm and evaluate suspected cases of murine inclusion body
      nephropathy.

PMID- 29061934
TI  - Experimental Animal Models of Arteriovenous Malformation: A Review.
AB  - Arteriovenous malformations (AVMs) are congenital lesions that cause brain
      haemorrhage in children and young adults. Current treatment modalities include
      surgery, radiosurgery and embolization. These treatments are generally effective
      only for small AVMs. Over one third of AVMs cannot be treated safely and
      effectively with existing options. Several animal models have been developed with
      the aims of understanding AVM pathophysiology and improving treatment. No animal
      model perfectly mimics a human AVM. Each model has limitations and advantages.
      Models contribute to the understanding of AVMs and hopefully to the development
      of improved therapies. This paper reviews animal models of AVMs and their
      advantages and disadvantages.

PMID- 29061936
TI  - The Establishment of the Pfizer-Canine Comparative Oncology and Genomics
      Consortium Biospecimen Repository.
AB  - The Canine Comparative Oncology and Genomics Consortium (CCOGC) was formed in
      2004 in an effort to capitalize on the generation of a domestic dog genome
      sequence assembly [1], which created new opportunities to investigate canine
      cancers at the molecular level [2]. [...].

PMID- 29061937
TI  - Twinning in Holstein-Friesian Dairy Cows: Proportion Carried to Term and Calf Sex
      Ratios.
AB  - The purpose of this study was to investigate the proportion of twins carried to
      term and the sex ratio of twin calves at birth in Holstein-Friesian dairy cattle
      kept on commercial farms in Devon and Cornwall, England. Ten farms were used in
      the study. Fifty four cows with twin pregnancies were identified using trans
      rectal ultra-sonographic examination between 30 and 70 days of gestation. The
      farm records were subsequently used to derive the number of calves born. Farm
      records of 66 additional sets of twin births with the sex of the calves recorded
      were also identified. Of the 54 cows diagnosed with twin pregnancies, 16 cows
      (29.6%) aborted or absorbed both fetuses, 11 cows (20.4%) carried one calf to
      term and 27 cows (50%) carried both calves to term. In the calf sex analysis of
      the additional 66 sets of twins: 13?? calves (19.7%), 18 ?? calves (27.3%) and 35
      ?? calves (53.0%). There was no statistically significant difference from an
      expected ratio of 1??:2??:1?? (p = 0.61). This study provides bench marks for the
      expected abortion/absorption rates following the early ultra-sonographic
      diagnosis of twin pregnancies in comparable populations and supports earlier
      observations that the expected sex ratio for twinning approximates to1??:2??:1??.

PMID- 29061935
TI  - Cats, Cancer and Comparative Oncology.
AB  - Naturally occurring tumors in dogs are well-established models for several human
      cancers. Domestic cats share many of the benefits of dogs as a model (spontaneous
      cancers developing in an immunocompetent animal sharing the same environment as
      humans, shorter lifespan allowing more rapid trial completion and data
      collection, lack of standard of care for many cancers allowing evaluation of
      therapies in treatment-naive populations), but have not been utilized to the same
      degree in the One Medicine approach to cancer. There are both challenges and
      opportunities in feline compared to canine models. This review will discuss three
      specific tumor types where cats may offer insights into human cancers. Feline
      oral squamous cell carcinoma is common, shares both clinical and molecular
      features with human head and neck cancer and is an attractive model for
      evaluating new therapies. Feline mammary tumors are usually malignant and
      aggressive, with the 'triple-negative' phenotype being more common than in
      humans, offering an enriched population in which to examine potential targets and
      treatments. Finally, although there is not an exact corollary in humans, feline
      injection site sarcoma may be a model for inflammation-driven tumorigenesis,
      offering opportunities for studying variations in individual susceptibility as
      well as preventative and therapeutic strategies.

PMID- 29061938
TI  - From "One Health" to "One Communication": The Contribution of Communication in
      Veterinary Medicine to Public Health.
AB  - Despite the fact that health communication is a discipline developed only
      recently, its importance in human medicine is well recognized. However, it is
      less considered in veterinary medicine, even if it has the potential to improve
      public health because of the role of veterinary medicine in public health. For
      this reason, an One Health approach is useful for communication as well. This
      approach leads to a "One Communication" concept, which is the result of the
      synergy in communicative efforts both in human and in veterinary medicine. Our
      analysis explores the potential of communication in several veterinary fields:
      institutions, food safety, companion animal and food-producing animal practice,
      pharmacology and drugs, wildlife fauna and environment. In almost all the areas
      of veterinary activity communication can contribute to human health. It takes
      many forms and use several channels, and this variety of communicative
      opportunities represent a challenge for veterinarians. For this reason, the
      communication course should be included in the curricula of Veterinary Medicine
      Schools. As One Health, One Communication is a strategy for expanding
      collaborations in health communication and it will enhance public health.

PMID- 29061941
TI  - Bacterial Loads on Skin of Unclipped Gluteal Sites Following Treatment with 70%
      Isopropyl Alcohol-Soaked Swabs in Dairy Cows.
AB  - The aim of this study was to compare the bacterial load of unclipped gluteal skin
      in dairy cows following either no treatment or treatment with a standard 70%
      isopropyl alcohol-based skin treatment protocol. Twenty Holstein-Friesian dairy
      cows from a commercial dairy herd in Cambridgeshire, England, were used in this
      randomised, blinded, controlled study. On each of the experimental cows an area
      of unclipped gluteal skin on one side of the pelvis was treated with swabs soaked
      in 70% isopropyl alcohol-based using a standard protocol and a contra-lateral
      area of skin was left untreated as a control. All the experimental skin sites
      were sampled using a swab followed by bacterial culture and quantitative analysis
      of bacterial load. There was a statistically significant decrease in the
      bacterial colony forming units per mL for the isopropyl-alcohol treatment group
      when compared to the control group (p <= 0.01). There was a 58% reduction in the
      median bacterial load of the treated sites when compared to the bacterial load of
      the untreated sites. This study has demonstrated that the treatment protocol will
      reduce the skin bacterial load.

PMID- 29061940
TI  - Comparative Aspects of Molecular Mechanisms of Drug Resistance through ABC
      Transporters and Other Related Molecules in Canine Lymphoma.
AB  - The most important causes of treatment failure in canine lymphoma include
      intrinsic or acquired drug resistance. Thus, elucidation of molecular mechanisms
      of drug resistance is essential for the establishment of better treatment
      alternatives for lymphoma patients. The overexpression of drug transporters is
      one of the most intensively studied mechanisms of drug resistance in many tumors.
      In canine lymphoma, it has also been shown that the overexpression of drug efflux
      pumps such as P-glycoprotein is associated with drug-resistant phenotypes. Canine
      lymphoma has many pathological similarities to human non-Hodgkin's lymphoma, and
      they also share similar molecular mechanisms of drug resistance. We have
      previously demonstrated the association of the overexpression of drug
      transporters with drug resistance and indicated some molecular mechanisms of the
      regulation of these transporters' expressions in canine and human lymphoid tumor
      cells. However, it has also been indicated that other known or novel drug
      resistance factors should be explored to overcome drug resistance in lymphoma. In
      this review, we summarize the recent findings on the molecular mechanisms of drug
      resistance and possible strategies to develop better treatment modalities for
      canine lymphoma from the comparative aspects with human lymphoid tumors.

PMID- 29061939
TI  - Mechanisms of Drug Resistance in Veterinary Oncology- A Review with an Emphasis
      on Canine Lymphoma.
AB  - Drug resistance (DR) is the major limiting factor in the successful treatment of
      systemic neoplasia with cytotoxic chemotherapy. DR can be either intrinsic or
      acquired, and although the development and clinical implications are different,
      the underlying mechanisms are likely to be similar. Most causes for DR are
      pharmacodynamic in nature, result from adaptations within the tumor cell and
      include reduced drug uptake, increased drug efflux, changes in drug metabolism or
      drug target, increased capacity to repair drug-induced DNA damage or increased
      resistance to apoptosis. The role of active drug efflux transporters, and those
      of the ABC-transporter family in particular, have been studied extensively in
      human oncology and to a lesser extent in veterinary medicine. Methods reported to
      assess ABC-transporter status include detection of the actual protein (Western
      blot, immunohistochemistry), mRNA or ABC-transporter function. The three major
      ABC-transporters associated with DR in human oncology are ABCB1 or P-gp, ABCC1 or
      MRP1, and ABCG2 or BCRP, and have been demonstrated in canine cell lines, healthy
      dogs and dogs with cancer. Although this supports a causative role for these ABC
      transporters in DR cytotoxic agents in the dog, the relative contribution to the
      clinical phenotype of DR in canine cancer remains an area of debate and requires
      further prospective studies.

PMID- 29061943
TI  - Comparative Aspects of BRAF Mutations in Canine Cancers.
AB  - Activating mutations of the BRAF gene lead to constitutive activation of the MAPK
      pathway. The characterization and discovery of BRAF mutations in a variety of
      human cancers has led to the development of specific inhibitors targeting the
      BRAF/MAPK pathway and dramatically changed clinical outcomes in BRAF-mutant
      melanoma patients. Recent discovery of BRAF mutation in canine cancers
      underscores the importance of MAPK pathway activation as an oncogenic molecular
      alteration evolutionarily conserved between species. A comparative approach using
      the domestic dog as a spontaneous cancer model will provide new insights into the
      dysregulation of BRAF/MAPK pathway in carcinogenesis and facilitate in vivo
      studies to evaluate therapeutic strategies targeting this pathway's molecules for
      cancer therapy. The BRAF mutation in canine cancers may also represent a
      molecular marker and therapeutic target in veterinary oncology. This review
      article summarizes the current knowledge on BRAF mutations in human and canine
      cancers and discusses the potential applications of this abnormality in
      veterinary oncology.

PMID- 29061942
TI  - Comparative Aspects of Osteosarcoma Pathogenesis in Humans and Dogs.
AB  - Osteosarcoma (OS) is a primary and aggressive bone sarcoma affecting the skeleton
      of two principal species, human beings and canines. The biologic behavior of OS
      is conserved between people and dogs, and evidence suggests that fundamental
      discoveries in OS biology can be facilitated through detailed and comparative
      studies. In particular, the relative genetic homogeneity associated with specific
      dog breeds can provide opportunities to facilitate the discovery of key genetic
      drivers involved in OS pathogenesis, which, to-date, remain elusive. In this
      review, known causative factors that predispose to the development OS in human
      beings and dogs are summarized in detail. Based upon the commonalities shared in
      OS pathogenesis, it is likely that foundational discoveries in one species will
      be translationally relevant to the other and emphasizes the unique opportunities
      that might be gained through comparative scientific approaches.

PMID- 29061944
TI  - Cytogenomics of Feline Cancers: Advances and Opportunities.
AB  - Relative to the dog, integration of the cat into the "One Health" concept has
      been more restricted, particularly in the field of molecular oncology. Beyond the
      continual need to enhance the sophistication of feline healthcare per se, the
      unique spectrum of naturally-occurring cancers in the cat offers tremendous
      opportunities for comparative and translational advances that may have mutual
      benefit for human and veterinary medicine. The study of feline cancers
      additionally may generate new insight into underexplored aspects of tumor biology
      that are less accessible in other species, such as the relationship between
      chronic inflammation and neoplasia, and the role of viruses in malignant
      transformation. Several factors that have hindered molecular studies of feline
      cancers have now been surmounted, with the most fundamental step forward coming
      from the development of a high-quality reference genome sequence assembly for the
      cat. This article reviews landmark studies that have led to our current
      appreciation of feline genome architecture, and outlines techniques used in
      cancer cytogenomics, from conventional karyotyping analysis through to the
      development of genomic microarrays and beyond. A summary of progress in the
      identification and characterization of chromosomal aberrations in feline cancers
      is provided using examples from studies of injection-site sarcomas, lymphomas and
      mammary tumors.

PMID- 29061945
TI  - Investigation of Anti-Myeloperoxidase Antibodies in a Dog with Bilateral
      Necrotizing Scleritis.
AB  - Necrotizing scleritis is uncommon in dogs and presumed to be immune-mediated. Its
      clinical pattern and histopathology are similar to ocular lesions observed in
      humans suffering from granulomatosis with polyangiitis (GPA), formerly named
      Wegener's granulomatosis, where the pathogenesis revolves around anti-neutrophil
      antibodies (e.g., anti-myeloperoxidase). These antibodies are used to diagnose
      and follow-up the disease in humans, but variants that only affect the eyes often
      test negative. Here, we present the first case of canine necrotizing scleritis
      where measurement of anti-myeloperoxidase antibodies was attempted. A 1.5 year
      old female Scottish Terrier was presented with bilateral deep multifocal
      scleromalacia, severe inflammation of corneal/uveal/retrobulbar tissues,
      perilimbal corneal oedema and neovascularization, hypotony, and mild
      exophthalmos. Corticosteroids and antibiotics had been administrated (topically
      and orally) without success. Due to painful multifocal scleral perforation with
      vitreal haemorrhage, the left eye underwent enucleation, so did the right eye one
      week later. The histopathology of the left eye revealed a neutrophilic and
      histiocytic scleral infiltration with extension of pyogranulomatous inflammation
      to the cornea, choroid, ciliary body, and orbital fat. Levels of plasma anti
      myeloperoxidase antibodies were not statistically significant to those of 13
      healthy dogs. Further research is warranted to investigate the presence and role
      of anti-neutrophil antibodies in canine necrotizing scleritis.

PMID- 29061946
TI  - Beta Adrenergic Signaling: A Targetable Regulator of Angiosarcoma and
      Hemangiosarcoma.
AB  - Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers
      thought to arise from cells of vascular origin. The pathological features,
      morphological organization, and clinical behavior of canine hemangiosarcomas are
      virtually indistinct from those of human angiosarcomas. Overall survival with
      current standard-of-care approaches remains dismal for both humans and dogs, and
      each is likely to succumb to their disease within a short duration. While
      angiosarcomas in humans are extremely rare, limiting their study and treatment
      options, canine hemangiosarcomas occur frequently. Therefore, studies of these
      sarcomas in dogs can be used to advance treatment approaches for both patient
      groups. Emerging data suggest that angiosarcomas and hemangiosarcomas utilize
      beta adrenergic signaling to drive their progression by regulating the tumor cell
      niche and fine-tuning cellular responses within the tumor microenvironment. These
      discoveries indicate that inhibition of beta adrenergic signaling could serve as
      an Achilles heel for these tumors and emphasize the need to design therapeutic
      strategies that target tumor cell and stromal cell constituents. In this review,
      we summarize recent discoveries and present new hypotheses regarding the roles of
      beta adrenergic signaling in angiosarcomas and hemangiosarcomas. Because the use
      of beta adrenergic receptor antagonists is well established in human and
      veterinary medicine, beta blockade could provide an immediate adjunct therapy for
      treatment along with a tangible opportunity to improve upon the outcomes of both
      humans and dogs with these diseases.

PMID- 29061948
TI  - Metabolite Profiles of Male and Female Humboldt Penguins.
AB  - We examined 185 metabolites in 30 adult Humboldt Penguins (Spheniscus humboldti)
      nesting at the Punta San Juan Marine Protected Area, Peru, in order to examine
      gender differences in metabolome profiles, particularly those involved in
      metabolism and energetics. The majority of the compounds identified were fatty
      (26% of total identified compounds), organic (19%), and amino (16%) acids. We
      were able to differentiate male and female penguins with 96.6% accuracy on the
      basis of 12 metabolites, most of which are involved in lipid and carbohydrate
      metabolism. These included 2-oxoglutarate, erythronic acid, GABA, mannitol,
      sedoheptulose 7-phosphate, and serine and six metabolites present in higher
      concentrations in females compared to males (2-aminoadipic acid, O
      phosphorylethanolamine, glycerol 2-phosphate, glycerol 3-phosphate, pantothenic
      acid, and creatinine). Of these, 2-oxoglutarate and glycerol 3-phosphate were key
      metabolites distinguishing gender. Our results indicated that male and female
      Humboldt Penguins were characterized by differing metabolic states. Such
      differences could be important to individual and brood survival in times of
      environmental stress.

PMID- 29061949
TI  - Pathobiology of Hemangiosarcoma in Dogs: Research Advances and Future
      Perspectives.
AB  - Hemangiosarcoma (HSA) is an aggressive and common cancer in dogs. While cutaneous
      masses are often treatable by tumor excision, visceral tumors are almost always
      incurable. Treatment advances for this disease have been limited due to a poor
      understanding of the overall tumor biology. Based upon its histological
      appearance, HSA has been presumed to originate from transformed endothelial
      cells; however, accumulating data now suggest a pluripotent bone marrow
      progenitor as the cell of origin for this disease. More recently, the
      identification of a novel subclassification of HSAs has provided a foundation to
      further our understanding of the cellular characteristics of HSA tumor cells,
      along with those of the cells comprising the tumor microenvironment. These
      discoveries hold promise for the development of new approaches to improve
      treatments for canine HSA, as well as to establish the utility of this disease as
      a spontaneous model to understand the pathogenesis and develop new treatments for
      vascular tumors of humans. In this review, we will provide a brief historical
      perspective and pathobiology of canine HSA, along with a focus on the recent
      advances in the molecular and cellular understanding of these tumors. In
      addition, future directions that should continue to improve our understanding of
      HSA pathogenesis will be discussed.

PMID- 29061950
TI  - Atlantic Bottlenose Dolphins (Tursiops truncatus) as A Sentinel for Exposure to
      Mercury in Humans: Closing the Loop.
AB  - Mercury (Hg) is a ubiquitous global contaminant with important public health
      implications. Mercury is released from a variety of anthropogenic, industrial
      processes, enters the earth's atmosphere and is re-deposited onto the earth's
      surface in rainfall. Much of this Hg enters the oceans which cover the majority
      of the earth's surface. In the marine environment, inorganic Hg is converted to
      the most toxic form of the element, methylmercury, and biomagnified through the
      trophic levels of the food web. The bottlenose dolphin (Tursiops truncatus) is
      the apex predator in many estuarine and coastal ecosystems. Due to their long
      life span and trophic position, bottlenose dolphins bioaccumulate high
      concentrations of contaminants including Hg, thus making them an important
      sentinel species for ecosystem and public health. Bottlenose dolphins in Florida
      bioaccumulate high concentrations of Hg in their blood, skin and internal organs.
      The concentrations of Hg in blood and skin of bottlenose dolphins of the Indian
      River Lagoon, FL (IRL) are among the highest reported world-wide. In previous
      studies, we demonstrated associations between concentrations of total Hg in the
      blood and skin of IRL dolphins and markers of endocrine, renal, hepatic,
      hematologic and immune system dysfunction. The predominant manifestation of
      exposure to mercury in humans is neurotoxicity. During the 1950s and 1960s,
      residents of Minamata bay, Japan were exposed to high concentrations of methyl
      mercury as the result of ingestion of fish and shellfish that had become
      contaminated in this infamous environmental disaster. Affected adults had severe
      motor and sensory abnormalities often leading to death. Methyl mercury crosses
      the placenta during pregnancy. Children exposed in utero were born with multiple
      congenital anomalies and also suffered from neurologic disorders. Significantly,
      local cats that consumed Hg contaminated fish developed severe signs of
      neurotoxicity which led to their subsequent description as the "dancing cats of
      Minamata bay". Unfortunately, the cause of these strange manifestations in cats
      was not recognized in time to prevent hundreds of additional cases from
      occurring. More recent studies have shown that exposure to mercury as a result of
      seafood consumption during pregnancy may result in multiple cognitive and
      neurodevelopmental effects in children. The levels of mercury found in bottlenose
      dolphins and the health effects we identified alerted us to the possibility of an
      important public health hazard. The IRL occupies 40 percent of the east coast of
      Florida and is bordered by counties with approximately 2.5 million human
      inhabitants. Therefore, we hypothesized that local inhabitants in communities
      bordering the IRL could be at risk of exposure to Hg from the consumption of fish
      and shellfish. We measured hair Hg in 135 local residents and found a mean
      concentration of 1.53 ug/g which was higher than that from previous studies of
      sport fishermen and coastal residents in other states. Over 50% of participants
      had a hair Hg concentration which exceeded the U.S. EPA exposure guideline. Hair
      Hg concentration was directly related to the frequency of seafood consumption and
      to the proportion of fish and shellfish obtained from local recreational sources.
      This study clearly exemplifies the importance of an animal sentinel in
      identifying a public health hazard and is virtually unique in "closing the loop"
      between animal and human health.

PMID- 29061952
TI  - Relative Bioavailability of Niacin Supplements for Dairy Cows: Effects of Rumen
      Protection and of Feed Processing.
AB  - The present study aimed to examine the effective systemic bioavailability of
      niacin- with particular focus on its galenic form-and feed processing. Experiment
      1 was conducted with 35 dairy cows to investigate the effects of various doses of
      oral supplemented nicotinic acid (NA) either in differing galenic forms (non
      rumen protected (nRP) vs. rumen protected form (RP)) on serum niacin
      concentrations. Experiment 2 was designed as a pharmacokinetic study examining
      the serum niacin kinetics over 24 h after giving a single oral bolus of 24 g nRP
      or RP NA admixed in either pelleted or ground concentrate. In both experiments,
      only the niacin vitamer nicotinamide (NAM) was detected. Results of experiment 1
      showed that both galenic forms at a dose of 24 g/cow daily elevated NAM
      concentrations at the beginning of the experiment. Despite a daily
      supplementation, NAM concentrations decreased continuously towards the end of the
      experiment which was more steeply in nRP NA (p = 0.03). On experimental day 21,
      NAM concentrations were higher when feeding RP NA (p = 0.03) and the highest dose
      (24 g/day and cow) (p < 0.01). Results of experiment 2 indicated that nRP and RP
      were characterized by similar pharmacokinetic profiles resulting in similar areas
      under the curves as a net result of the kinetic counterbalancing alterations.
      Pelleting seemed not to influence the relative bioavailability.

PMID- 29061951
TI  - Manipulation of Innate Immunity for Cancer Therapy in Dogs.
AB  - Over the last one to two decades, the field of cancer immunotherapy has rapidly
      progressed from early preclinical studies to a successful clinical reality and
      fourth major pillar of human cancer therapy. While current excitement in the
      field of immunotherapy is being driven by several major breakthroughs including
      immune checkpoint inhibitors and adoptive cell therapies, these advances stem
      from a foundation of pivotal studies demonstrating the immune systems role in
      tumor control and eradication. The following will be a succinct review on
      veterinary cancer immunotherapy as it pertains to manipulation of the innate
      immune system to control tumor growth and metastasis. In addition, we will
      provide an update on recent progress in our understanding of the innate immune
      system in veterinary tumor immunology, and how these gains may lead to novel
      therapies for the treatment of cancer in companion animals.

PMID- 29061954
TI  - A Tactile Sensor Network System Using a Multiple Sensor Platform with a Dedicated
      CMOS-LSI for Robot Applications.
AB  - Robot tactile sensation can enhance human-robot communication in terms of safety,
      reliability and accuracy. The final goal of our project is to widely cover a
      robot body with a large number of tactile sensors, which has significant
      advantages such as accurate object recognition, high sensitivity and high
      redundancy. In this study, we developed a multi-sensor system with dedicated
      Complementary Metal-Oxide-Semiconductor (CMOS) Large-Scale Integration (LSI)
      circuit chips (referred to as "sensor platform LSI") as a framework of a serial
      bus-based tactile sensor network system. The sensor platform LSI supports three
      types of sensors: an on-chip temperature sensor, off-chip capacitive and
      resistive tactile sensors, and communicates with a relay node via a bus line. The
      multi-sensor system was first constructed on a printed circuit board to evaluate
      basic functions of the sensor platform LSI, such as capacitance-to-digital and
      resistance-to-digital conversion. Then, two kinds of external sensors, nine
      sensors in total, were connected to two sensor platform LSIs, and temperature,
      capacitive and resistive sensing data were acquired simultaneously. Moreover, we
      fabricated flexible printed circuit cables to demonstrate the multi-sensor system
      with 15 sensor platform LSIs operating simultaneously, which showed a more
      realistic implementation in robots. In conclusion, the multi-sensor system with
      up to 15 sensor platform LSIs on a bus line supporting temperature, capacitive
      and resistive sensing was successfully demonstrated.

PMID- 29061953
TI  - Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus.
AB  - Feline immunodeficiency virus (FIV) is one of the most common infectious agents
      affecting cats worldwide .FIV and human immunodeficiency virus (HIV) share many
      properties: both are lifelong persistent lentiviruses that are similar
      genetically and morphologically and both viruses propagate in T-lymphocytes,
      macrophages, and neural cells. Experimentally infected cats have measurable
      immune suppression, which sometimes progresses to an acquired immunodeficiency
      syndrome. A transient initial state of infection is followed by a long latent
      stage with low virus replication and absence of clinical signs. In the terminal
      stage, both viruses can cause severe immunosuppression. Thus, FIV infection in
      cats has become an important natural model for studying HIV infection in humans,
      especially for evaluation of antiviral compounds. Of particular importance for
      chemotherapeutic studies is the close similarity between the reverse
      transcriptase (RT) of FIV and HIV, which results in high in vitro susceptibility
      of FIV to many RT-targeted antiviral compounds used in the treatment of HIV
      infected patients. Thus, the aim of this article is to provide an up-to-date
      review of studies on antiviral treatment of FIV, focusing on commercially
      available compounds for human or animal use.

PMID- 29061947
TI  - Comparative Analysis of Tat-Dependent and Tat-Deficient Natural Lentiviruses.
AB  - The emergence of human immunodeficiency virus (HIV) causing acquired
      immunodeficiency syndrome (AIDS) in infected humans has resulted in a global
      pandemic that has killed millions. HIV-1 and HIV-2 belong to the lentivirus genus
      of the Retroviridae family. This genus also includes viruses that infect other
      vertebrate animals, among them caprine arthritis-encephalitis virus (CAEV) and
      Maedi-Visna virus (MVV), the prototypes of a heterogeneous group of viruses known
      as small ruminant lentiviruses (SRLVs), affecting both goat and sheep worldwide.
      Despite their long host-SRLV natural history, SRLVs were never found to be
      responsible for immunodeficiency in contrast to primate lentiviruses. SRLVs only
      replicate productively in monocytes/macrophages in infected animals but not in
      CD4+ T cells. The focus of this review is to examine and compare the biological
      and pathological properties of SRLVs as prototypic Tat-independent lentiviruses
      with HIV-1 as prototypic Tat-dependent lentiviruses. Results from this analysis
      will help to improve the understanding of why and how these two prototypic
      lentiviruses evolved in opposite directions in term of virulence and
      pathogenicity. Results may also help develop new strategies based on the
      attenuation of SRLVs to control the highly pathogenic HIV-1 in humans.

PMID- 29061955
TI  - Double Hydrogen Bonding between Side Chain Carboxyl Groups in Aqueous Solutions
      of Poly (beta-L-Malic Acid): Implication for the Evolutionary Origin of Nucleic
      Acids.
AB  - The RNA world hypothesis holds that in the evolutionary events that led to the
      emergence of life RNA preceded proteins and DNA and is supported by the ability
      of RNA to act as both a genetic polymer and a catalyst. On the other hand,
      biosynthesis of nucleic acids requires a large number of enzymes and chemical
      synthesis of RNA under presumed prebiotic conditions is complicated and requires
      many sequential steps. These observations suggest that biosynthesis of RNA is the
      end product of a long evolutionary process. If so, what was the original polymer
      from which RNA and DNA evolved? In most syntheses of simpler RNA or DNA analogs,
      the D-ribose phosphate polymer backbone is altered and the purine and pyrimidine
      bases are retained for hydrogen bonding between complementary base pairs.
      However, the bases are themselves products of complex biosynthetic pathways and
      hence they too may have evolved from simpler polymer side chains that had the
      ability to form hydrogen bonds. We hypothesize that the earliest evolutionary
      predecessor of nucleic acids was the simple linear polyester, poly (beta-D-malic
      acid), for which the carboxyl side chains could form double hydrogen bonds. In
      this study, we show that in accord with this hypothesis a closely related
      polyester, poly (beta-L-malic acid), uses carboxyl side chains to form robust
      intramolecular double hydrogen bonds in moderately acidic solution.

PMID- 29061956
TI  - Oxycodone Resistance Due to Rifampin Use in an Osteosarcoma Patient with
      Tuberculosis.
AB  - BACKGROUND Oxycodone is a semisynthetic opioid receptor agonist, and is
      frequently used for pain control in patients with cancer. Most oxycodone is
      metabolized by N-demethylation to noroxycodone by CYP3A. Rifampin is a strong
      inducer of several drug-metabolizing enzymes, including CYP3A. Hence, rifampin
      induced CYP3A activity may decrease the effect of oxycodone. CASE REPORT
      Osteosarcoma is a highly aggressive primary bone tumor of childhood and
      adolescence. Here, we report a 30-year-old male with osteosarcoma of the femur
      with lung metastases in the upper lobe. The lung also contained small, scattered
      nodular lesions that were identified as tuberculosis. Multi-drug therapy,
      including rifampin, was administered. The upper-lobe metastatic lesion extended
      to the brachial plexus and caused severe pain. Over 1000 mg per day of oxycodone
      was ineffective for pain control. However, morphine was able to control his pain
      at about one-third the equivalent dose. CONCLUSIONS Our patient demonstrated
      oxycodone resistance due to rifampin. Chemotherapy may have compromised the
      patient's immune system, thus theoretically increasing the risk of tuberculosis.
      Recognition of the interactions between rifampin and oxycodone is important in
      this and other cancers. Notably, for patients using high doses of oxycodone to
      manage severe pain, stopping rifampin may lead to oxycodone overdose.

PMID- 29061958
TI  - alpha-Linolenic Acid Inhibits Receptor Activator of NF-kappaB Ligand Induced
      (RANKL-Induced) Osteoclastogenesis and Prevents Inflammatory Bone Loss via
      Downregulation of Nuclear Factor-KappaB-Inducible Nitric Oxide Synthases (NF
      kappaB-iNOS) Signaling Pathways.
AB  - BACKGROUND Inflammation is a major cellular strain causing increased risk of
      osteo-degenerative diseases. Omega-3 fatty acids have been great source in
      suppressing inflammation. We investigated the effect of alpha-linolenic acid
      (ALA) on RANKL-stimulated osteoclast differentiation, LPS-induced and
      ovariectomized bone loss in mice models. MATERIAL AND METHODS The bone marrow
      macrophages (BMMs) were isolated from femurs of ICR mice, stimulated with RANKL,
      and treated with ALA (100, 200, 300 uM). Major analytical methods include
      histological analysis, osteoclasts viability assay, serum cytokines and
      chemokines ELISA, and gene expression by qPCR. RESULTS ALA intervention inhibited
      RANKL-induced osteoclasts proliferation and differentiation. ALA inhibited bone
      resorption activity as measured by materialization of F-actin ring structures as
      well. ALA suppressed the RANKL-induced osteoclast markers c-Fos, c-Jun and NFATc1
      together with transcription factor proteins TRAP, OSCAR, cathepsin K and beta3
      integrin. ALA also suppressed the RANKL-stimulated phosphorylation of JNK, ERK,
      and AKT as well as NF-kappaB and BCL-2 proteins. ALA intervention (100 and 300
      mg/kg) to LPS-challenged mice showed annulled morphometric changes induced by LPS
      by suppressing the levels of proinflammatory cytokines and chemokines. ALA (100
      and 300 mg/kg) intervention to estrogen-deficiency induced bone loss mice
      (ovariectomized) showed reductions in TRAP+ osteoclasts count, CTX-I expression,
      levels of IL-1beta, IL-2, IL-6, IL10, TNF-alpha and MCP-1 and iNOS and COX-2.
      CONCLUSIONS ALA suppresses RANKL-induced osteoclast differentiation and prevents
      inflammatory bone loss via downregulation of NF-kappaB-iNOS-COX-2 signaling. ALA
      is suggested to be a preventive herbal medicine against inflammatory bone
      disorders.

PMID- 29061957
TI  - Negative Correlation Between Hepatitis C Virus (HCV) and Let-7 MicroRNA Family in
      Transplanted Livers: The Role of rs868 Single-Nucleotide Polymorphism.
AB  - BACKGROUND Genetic alterations of TGF-beta pathway members, including its
      transmembrane receptor, TGFBR1, may influence the course of HCV infection. Rs868
      is a single-nucleotide polymorphism of the 3'UTR region of TGFBR1, located in a
      binding site for the conserved let-7/miR98 microRNA family. Previously, we
      demonstrated a favorable course of hepatitis C recurrence after liver
      transplantation in rs868 AG genotype of the transplanted liver when compared to
      rs868 AA. The aim of the present study was to confirm the biological effect of
      rs868. MATERIAL AND METHODS HepG2 cell line was transfected with luciferase
      vectors cloned with 3'UTR of TGFBR1 gene encompassing different rs868 alleles.
      Post-transplant liver biopsies from 61 patients with HCV-related end-stage liver
      disease were evaluated histopathologically and analyzed for the expression of
      TGFBR1 mRNA, let-7/miR98 microRNAs, HCV RNA load, and rs868 genotype. RESULTS
      Luciferase expression was significantly lower in the A allele-containing vector.
      TGFBR1 mRNA and HCV RNA load were correlated negatively with let-7/miR98
      microRNAs and this correlation was significantly stronger for rs868 AG compared
      to AA genotype. A strong positive correlation was demonstrated between TGFBR1 and
      HCV in both genotypes. In AG heterozygotes, let-7/miR98 microRNAs showed a strong
      negative correlation with periportal or periseptal interface hepatitis (Ishak A
      score). CONCLUSIONS There is a negative correlation between let-7/miR98 microRNAs
      and HCV viral load and TGFBR1 mRNA after liver transplantation. In the rs868 AG
      heterozygotes, this correlation was stronger and there was a negative correlation
      between let-7/miR98 and Ishak A score, which is in concordance with the
      previously demonstrated protective role of this genotype in post-transplant
      hepatitis C recurrence.

PMID- 29061959
TI  - Dynamics of lineage commitment revealed by single-cell transcriptomics of
      differentiating embryonic stem cells.
AB  - Gene expression heterogeneity in the pluripotent state of mouse embryonic stem
      cells (mESCs) has been increasingly well-characterized. In contrast, exit from
      pluripotency and lineage commitment have not been studied systematically at the
      single-cell level. Here we measure the gene expression dynamics of retinoic acid
      driven mESC differentiation from pluripotency to lineage commitment, using an
      unbiased single-cell transcriptomics approach. We find that the exit from
      pluripotency marks the start of a lineage transition as well as a transient phase
      of increased susceptibility to lineage specifying signals. Our study reveals
      several transcriptional signatures of this phase, including a sharp increase of
      gene expression variability and sequential expression of two classes of
      transcriptional regulators. In summary, we provide a comprehensive analysis of
      the exit from pluripotency and lineage commitment at the single cell level, a
      potential stepping stone to improved lineage manipulation through timing of
      differentiation cues.

PMID- 29061962
TI  - Erratum: Self-assembly of ordered graphene nanodot arrays.
AB  - Change History: A correction to this article has been published and is linked
      from the HTML version of this article.

PMID- 29061960
TI  - Single-cell mass cytometry and transcriptome profiling reveal the impact of
      graphene on human immune cells.
AB  - Understanding the biomolecular interactions between graphene and human immune
      cells is a prerequisite for its utilization as a diagnostic or therapeutic tool.
      To characterize the complex interactions between graphene and immune cells, we
      propose an integrative analytical pipeline encompassing the evaluation of
      molecular and cellular parameters. Herein, we use single-cell mass cytometry to
      dissect the effects of graphene oxide (GO) and GO functionalized with amino
      groups (GONH2) on 15 immune cell populations, interrogating 30 markers at the
      single-cell level. Next, the integration of single-cell mass cytometry with
      genome-wide transcriptome analysis shows that the amine groups reduce the
      perturbations caused by GO on cell metabolism and increase biocompatibility.
      Moreover, GONH2 polarizes T-cell and monocyte activation toward a T helper-1/M1
      immune response. This study describes an innovative approach for the analysis of
      the effects of nanomaterials on distinct immune cells, laying the foundation for
      the incorporation of single-cell mass cytometry on the experimental pipeline.

PMID- 29061961
TI  - Survival of pancreatic cancer cells lacking KRAS function.
AB  - Activating mutations in the proto-oncogene KRAS are a hallmark of pancreatic
      ductal adenocarcinoma (PDAC), an aggressive malignancy with few effective
      therapeutic options. Despite efforts to develop KRAS-targeted drugs, the absolute
      dependence of PDAC cells on KRAS remains incompletely understood. Here we model
      complete KRAS inhibition using CRISPR/Cas-mediated genome editing and demonstrate
      that KRAS is dispensable in a subset of human and mouse PDAC cells. Remarkably,
      nearly all KRAS deficient cells exhibit phosphoinositide 3-kinase (PI3K)
      dependent mitogen-activated protein kinase (MAPK) signaling and induced
      sensitivity to PI3K inhibitors. Furthermore, comparison of gene expression
      profiles of PDAC cells retaining or lacking KRAS reveal a role of KRAS in the
      suppression of metastasis-related genes. Collectively, these data underscore the
      potential for PDAC resistance to even the very best KRAS inhibitors and provide
      insights into mechanisms of response and resistance to KRAS inhibition.

PMID- 29061963
TI  - alphav integrins on mesenchymal cells regulate skeletal and cardiac muscle
      fibrosis.
AB  - Mesenchymal cells expressing platelet-derived growth factor receptor beta
      (PDGFRbeta) are known to be important in fibrosis of organs such as the liver and
      kidney. Here we show that PDGFRbeta+ cells contribute to skeletal muscle and
      cardiac fibrosis via a mechanism that depends on alphav integrins. Mice in which
      alphav integrin is depleted in PDGFRbeta+ cells are protected from cardiotoxin
      and laceration-induced skeletal muscle fibrosis and angiotensin II-induced
      cardiac fibrosis. In addition, a small-molecule inhibitor of alphav integrins
      attenuates fibrosis, even when pre-established, in both skeletal and cardiac
      muscle, and improves skeletal muscle function. alphav integrin blockade also
      reduces TGFbeta activation in primary human skeletal muscle and cardiac
      PDGFRbeta+ cells, suggesting that alphav integrin inhibitors may be effective for
      the treatment and prevention of a broad range of muscle fibroses.

PMID- 29061965
TI  - Hierarchical control of enzymatic actuators using DNA-based switchable memories.
AB  - Inspired by signaling networks in living cells, DNA-based programming aims for
      the engineering of biochemical networks capable of advanced regulatory and
      computational functions under controlled cell-free conditions. While regulatory
      circuits in cells control downstream processes through hierarchical layers of
      signal processing, coupling of enzymatically driven DNA-based networks to
      downstream processes has rarely been reported. Here, we expand the scope of
      molecular programming by engineering hierarchical control of enzymatic actuators
      using feedback-controlled DNA-circuits capable of advanced regulatory dynamics.
      We developed a translator module that converts signaling molecules from the
      upstream network to unique DNA strands driving downstream actuators with minimal
      retroactivity and support these findings with a detailed computational analysis.
      We show our modular approach by coupling of a previously engineered switchable
      memories circuit to downstream actuators based on beta-lactamase and luciferase.
      To the best of our knowledge, our work demonstrates one of the most advanced DNA
      based circuits regarding complexity and versatility.

PMID- 29061964
TI  - Sparse synaptic connectivity is required for decorrelation and pattern separation
      in feedforward networks.
AB  - Pattern separation is a fundamental function of the brain. The divergent
      feedforward networks thought to underlie this computation are widespread, yet
      exhibit remarkably similar sparse synaptic connectivity. Marr-Albus theory
      postulates that such networks separate overlapping activity patterns by mapping
      them onto larger numbers of sparsely active neurons. But spatial correlations in
      synaptic input and those introduced by network connectivity are likely to
      compromise performance. To investigate the structural and functional determinants
      of pattern separation we built models of the cerebellar input layer with
      spatially correlated input patterns, and systematically varied their synaptic
      connectivity. Performance was quantified by the learning speed of a classifier
      trained on either the input or output patterns. Our results show that sparse
      synaptic connectivity is essential for separating spatially correlated input
      patterns over a wide range of network activity, and that expansion and
      correlations, rather than sparse activity, are the major determinants of pattern
      separation.

PMID- 29061966
TI  - Experimental measurement-device-independent quantum digital signatures.
AB  - The development of quantum networks will be paramount towards practical and
      secure telecommunications. These networks will need to sign and distribute
      information between many parties with information-theoretic security, requiring
      both quantum digital signatures (QDS) and quantum key distribution (QKD). Here,
      we introduce and experimentally realise a quantum network architecture, where the
      nodes are fully connected using a minimum amount of physical links. The central
      node of the network can act either as a totally untrusted relay, connecting the
      end users via the recently introduced measurement-device-independent (MDI)-QKD,
      or as a trusted recipient directly communicating with the end users via QKD.
      Using this network, we perform a proof-of-principle demonstration of QDS mediated
      by MDI-QKD. For that, we devised an efficient protocol to distil multiple
      signatures from the same block of data, thus reducing the statistical
      fluctuations in the sample and greatly enhancing the final QDS rate in the finite
      size scenario.

PMID- 29061968
TI  - Comprehensive assessment of the safety of olodaterol 5 ug in the Respimat(r)
      device for maintenance treatment of COPD: comparison with the long-acting beta2
      agonist formoterol.
AB  - This analysis provides a comprehensive clinical assessment of the long-term
      safety of the licensed dose of olodaterol (5 ug once daily [QD] via Respimat(r)
      inhaler) in patients with chronic obstructive pulmonary disease by exploring the
      occurrence of acknowledged side effects of long-acting beta2-agonists as well as
      those included in the olodaterol and formoterol labels. We analysed pooled data
      from two replicate, double-blind studies of olodaterol (5 ug QD via Respimat(r))
      compared to formoterol (12 ug twice daily [BID]) or placebo over 48 weeks
      (1222.13, NCT00793624; 1222.14, NCT00796653). Patients could continue their
      background treatment. The analysis considered adverse events (AEs) typically
      associated with beta2-agonists, including cardiovascular events, as well as
      administration-related events. Descriptive statistics were provided for the
      incidence of AEs and aggregated AEs. The analysis included 1379 patients: 460
      placebo, 459 olodaterol and 460 formoterol; AEs were reported by 70.9, 71.7 and
      69.1% of patients, respectively. Exposure-adjusted incidence rates of cardiac AEs
      (arrhythmia and myocardial ischaemia) and cough were numerically lower in the
      olodaterol group than the formoterol group, while nasopharyngitis, throat
      irritation, metabolism and psychiatric disorders were numerically higher in the
      olodaterol group. The most frequent event in the olodaterol group was
      nasopharyngitis (placebo 8.0%; olodaterol 12.9%; formoterol 10.0%). Except for
      cough (incidence rate ratio of 0.46 [95% confidence interval 0.24, 0.89] in
      favour of olodaterol), there were no significant differences between active
      groups. In conclusion, olodaterol 5 ug QD was well tolerated over 48 weeks with a
      typical beta2-agonist safety profile comparable to formoterol 12 ug BID.

PMID- 29061967
TI  - High grade serous ovarian carcinomas originate in the fallopian tube.
AB  - High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian
      cancer and has a poor outcome. It has been proposed that fallopian tube cancers
      may be precursors of HGSOC but evolutionary evidence for this hypothesis has been
      limited. Here, we perform whole-exome sequence and copy number analyses of laser
      capture microdissected fallopian tube lesions (p53 signatures, serous tubal
      intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian
      cancers, and metastases from nine patients. The majority of tumor-specific
      alterations in ovarian cancers were present in STICs, including those affecting
      TP53, BRCA1, BRCA2 or PTEN. Evolutionary analyses reveal that p53 signatures and
      STICs are precursors of ovarian carcinoma and identify a window of 7 years
      between development of a STIC and initiation of ovarian carcinoma, with
      metastases following rapidly thereafter. Our results provide insights into the
      etiology of ovarian cancer and have implications for prevention, early detection
      and therapeutic intervention of this disease.

PMID- 29061969
TI  - Direct benefits explain interspecific variation in helping behaviour among
      cooperatively breeding birds.
AB  - Kin selection theory provides one important explanation for seemingly altruistic
      helping behaviour by non-breeding subordinates in cooperative breeding animals.
      However, it cannot explain why helpers in many species provide energetically
      costly care to unrelated offspring. Here, I use comparative analyses to show that
      direct fitness benefits of helping others, associated with future opportunities
      to breed in the resident territory, are responsible for the widespread variation
      in helping effort (offspring food provisioning) and kin discrimination across
      cooperatively breeding birds. In species where prospects of territory inheritance
      are larger, subordinates provide more help, and, unlike subordinates that cannot
      inherit a territory, do not preferentially direct care towards related offspring.
      Thus, while kin selection can underlie helping behaviour in some species, direct
      benefits are much more important than currently recognised and explain why
      unrelated individuals provide substantial help in many bird species.

PMID- 29061971
TI  - The implications of dust ice nuclei effect on cloud top temperature in a complex
      mesoscale convective system.
AB  - Mineral dust is the most important natural source of atmospheric ice nuclei (IN)
      which may significantly mediate the properties of ice cloud through heterogeneous
      nucleation and lead to crucial impacts on hydrological and energy cycle. The
      potential dust IN effect on cloud top temperature (CTT) in a well-developed
      mesoscale convective system (MCS) was studied using both satellite observations
      and cloud resolving model (CRM) simulations. We combined satellite observations
      from passive spectrometer, active cloud radar, lidar, and wind field simulations
      from CRM to identify the place where ice cloud mixed with dust particles. For
      given ice water path, the CTT of dust-mixed cloud is warmer than that in
      relatively pristine cloud. The probability distribution function (PDF) of CTT for
      dust-mixed clouds shifted to the warmer end and showed two peaks at about -45 
      degrees C and -25  degrees C. The PDF for relatively pristine cloud only show one
      peak at -55  degrees C. Cloud simulations with different microphysical schemes
      agreed well with each other and showed better agreement with satellite
      observations in pristine clouds, but they showed large discrepancies in dust
      mixed clouds. Some microphysical schemes failed to predict the warm peak of CTT
      related to heterogeneous ice formation.

PMID- 29061972
TI  - Quantum size effect on charges and phonons ultrafast dynamics in atomically
      controlled nanolayers of topological insulators Bi2Te3.
AB  - Heralded as one of the key elements for next generation spintronics devices,
      topological insulators (TIs) are now step by step envisioned as nanodevices like
      charge-to-spin current conversion or as Dirac fermions based nanometer Schottky
      diode for example. However, reduced to few nanometers, TIs layers exhibit a
      profound modification of the electronic structure and the consequence of this
      quantum size effect on the fundamental carriers and phonons ultrafast dynamics
      has been poorly investigated so far. Here, thanks to a complete study of a set of
      high quality molecular beam epitaxy grown nanolayers, we report the existence of
      a critical thickness of around ~6 nm, below which a spectacular reduction of the
      carrier relaxation time by a factor of ten is found in comparison to bulk Bi2 Te3
      In addition, we also evidence an A1g optical phonon mode softening together with
      the appearance of a thickness dependence of the photoinduced coherent acoustic
      phonons signals. This drastic evolution of the carriers and phonons dynamics
      might be due an important electron-phonon coupling evolution due to the quantum
      confinement. These properties have to be taken into account for future TIs-based
      spintronic devices.

PMID- 29061970
TI  - White matter microstructure is associated with functional, cognitive and
      emotional symptoms 12 months after mild traumatic brain injury.
AB  - Identifying patients at risk of poor outcome after mild traumatic brain injury
      (MTBI) is essential to aid prognostics and treatment. Diffuse axonal injury (DAI)
      may be the primary pathologic feature of MTBI but is normally not detectable by
      conventional imaging technology. This lack of sensitivity of clinical imaging
      techniques has impeded a pathophysiologic understanding of the long-term
      cognitive and emotional consequences of MTBI, which often remain unnoticed and
      are attributed to factors other than the injury. Diffusion tensor imaging (DTI)
      is sensitive to microstructural properties of brain tissue and has been suggested
      to be a promising candidate for the detection of DAI in vivo. In this study, we
      report strong associations between brain white matter DTI and self-reported
      cognitive, somatic and emotional symptoms at 12 months post-injury in 134 MTBI
      patients. The anatomical distribution suggested global associations, in line with
      the diffuse symptomatology, although the strongest effects were found in frontal
      regions including the genu of the corpus callosum and the forceps minor. These
      findings support the hypothesis that DTI may provide increased sensitivity to the
      diffuse pathophysiology of MTBI and suggest an important role of advanced
      Magnetic Resonance Imaging (MRI) in trauma care.

PMID- 29061974
TI  - Novel anammox bacteria and nitrogen loss from Lake Superior.
AB  - Anaerobic ammonium oxidizing (anammox) bacteria own a central position in the
      global N-cycle, as they have the ability to oxidize NH4+ to N2 under anoxic
      conditions using NO2-. They are responsible for up to 50% of all N2 released from
      marine ecosystems into the atmosphere and are thus indispensible for balancing
      the activity of N-fixing bacteria and completing the marine N-cycle. The
      contribution, diversity, and impact of anammox bacteria in freshwater ecosystems,
      however, is largely unknown, confounding assessments of their role in the global
      N-cycle. Here we report the activity and diversity of anammox bacteria in the
      world's largest freshwater lake-Lake Superior. We found that anammox performed by
      previously undiscovered bacteria is an important contributor to sediment N2
      production. We observed striking differences in the anammox bacterial populations
      found at different locations within Lake Superior and those described from other
      locations. Our data thus reveal that novel anammox bacteria underpin N-loss from
      Lake Superior, and if more broadly distributed across inland waters would play an
      important role in continental N-cycling and mitigation of fixed nitrogen transfer
      from land to the sea.

PMID- 29061973
TI  - The Efficacy and Pharmacological Mechanism of Zn7MT3 to Protect against
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is one of the leading causes of death for people over 65
      years. Worse still, no completely effective therapeutic agent is available so
      far. One important pathological hallmark of AD is accumulated amyloid-beta
      (Abeta) plaques with dysregulated metal homeostasis. Human metallothionin 3
      (MT3), a regulator of metal homeostasis, is downregulated at least 30% in AD
      brain. So far, some in vitro studies demonstrated its multiple functions related
      to AD. However, it is a great pity that systematic in vivo studies of MT3 on AD
      model animals are still a blank so far. In this study, we treated APP/PS1 mice
      with sustained drug release of Zn7MT3 directly to the central nervous system, and
      investigated the role and molecular mechanism of Zn7MT3 to protect against AD
      mice systematically. The results demonstrated that Zn7MT3 can significantly
      ameliorate cognitive deficits, regulate metal homeostasis, abolish Abeta plaque
      load, and reduce oxidative stress. Additionally, it has been confirmed that MT3
      is penetrable to the blood brain barrier of AD mice. All these results support
      that Zn7MT3 is an effective AD suppressing agent and has potential for
      applications in Alzheimer's disease therapy.

PMID- 29061975
TI  - How aging impacts skin biomechanics: a multiscale study in mice.
AB  - Skin aging is a complex process that strongly affects the mechanical behavior of
      skin. This study aims at deciphering the relationship between age-related changes
      in dermis mechanical behavior and the underlying changes in dermis
      microstructure. To that end, we use multiphoton microscopy to monitor the
      reorganization of dermal collagen during mechanical traction assays in ex vivo
      skin from young and old mice. The simultaneous variations of a full set of
      mechanical and microstructural parameters are analyzed in the framework of a
      multiscale mechanical interpretation. They show consistent results for wild-type
      mice as well as for genetically-modified mice with modified collagen V synthesis.
      We mainly observe an increase of the tangent modulus and a lengthening of the
      heel region in old murine skin from all strains, which is attributed to two
      different origins that may act together: (i) increased cross-linking of collagen
      fibers and (ii) loss of water due to proteoglycans deterioration, which impedes
      inner sliding within these fibers. In contrast, the microstructure reorganization
      upon stretching shows no age-related difference, which can be attributed to
      opposite effects of the decrease of collagen content and of the increase of
      collagen cross-linking in old mice.

PMID- 29061977
TI  - A comparative Raman study between PrMnO 3, NdMnO 3, TbMnO 3 and DyMnO 3.
AB  - In this paper, we present a detailed Raman study of the non-multiferroic
      compounds PrMnO 3 and NdMnO 3 and the multiferroic compounds TbMnO 3 and DyMnO 3
      as a function of temperature and magnetic field. All studied systems show
      anomalous phonon shifts close to the Neel transition T N . In PrMnO 3 and NdMnO
      3, the frequency softenings are partly attributed to an orbital-spin-phonon
      coupling whereas in TbMnO 3 and DyMnO 3, the relatively weak frequency shifts are
      rather attributed to an expansion of the Mn-O bond lengths. On the other hand,
      the frequencies of TbMnO 3 phonons are shifted as a function of magnetic field,
      while those of PrMnO 3 remain unaffected. These frequency shifts are interpreted
      in terms of local oxygen rearrangements under magnetic field that could play an
      important role in the multiferroicity of TbMnO 3 and DyMnO 3.

PMID- 29061976
TI  - Ontology-based systematical representation and drug class effect analysis of
      package insert-reported adverse events associated with cardiovascular drugs used
      in China.
AB  - With increased usage of cardiovascular drugs (CVDs) for treating cardiovascular
      diseases, it is important to analyze CVD-associated adverse events (AEs). In this
      study, we systematically collected package insert-reported AEs associated with
      CVDs used in China, and developed and analyzed an Ontology of Cardiovascular Drug
      AEs (OCVDAE). Extending the Ontology of AEs (OAE) and NDF-RT, OCVDAE includes 194
      CVDs, CVD ingredients, mechanisms of actions (MoAs), and CVD-associated 736 AEs.
      An AE-specific drug class effect is defined to exist when all the drugs (drug
      chemical ingredients or drug products) in a drug class are associated with an AE,
      which is formulated as a new proportional class level ratio ("PCR") = 1. Our PCR
      based heatmap analysis identified many class level drug effects on different AE
      classes such as behavioral and neurological AE and digestive system AE.
      Additional drug-AE correlation tests (i.e., class-level PRR, Chi-squared, and
      minimal case reports) were also modified and applied to further detect
      statistically significant drug class effects. Two drug ingredient classes and
      three CVD MoA classes were found to have statistically significant class effects
      on 13 AEs. For example, the CVD Active Transporter Interactions class (including
      reserpine, indapamide, digoxin, and deslanoside) has statistically significant
      class effect on anorexia and diarrhea AEs.

PMID- 29061978
TI  - The structure of the human ABC transporter ABCG2 reveals a novel mechanism for
      drug extrusion.
AB  - The human ABC transporter ABCG2 (Breast Cancer Resistance Protein, BCRP) is
      implicated in anticancer resistance, in detoxification across barriers and linked
      to gout. Here, we generate a novel atomic model of ABCG2 using the crystal
      structure of ABCG5/G8. Extensive mutagenesis verifies the structure, disclosing
      hitherto unrecognized essential residues and domains in the homodimeric ABCG2
      transporter. The elbow helix, the first intracellular loop (ICL1) and the
      nucleotide-binding domain (NBD) constitute pivotal elements of the architecture
      building the transmission interface that borders a central cavity which acts as a
      drug trap. The transmission interface is stabilized by salt-bridge interactions
      between the elbow helix and ICL1, as well as within ICL1, which is essential to
      control the conformational switch of ABCG2 to the outward-open drug-releasing
      conformation. Importantly, we propose that ICL1 operates like a molecular spring
      that holds the NBD dimer close to the membrane, thereby enabling efficient
      coupling of ATP hydrolysis during the catalytic cycle. These novel mechanistic
      data open new opportunities to therapeutically target ABCG2 in the context of
      related diseases.

PMID- 29061979
TI  - hiPSC-CM Monolayer Maturation State Determines Drug Responsiveness in High
      Throughput Pro-Arrhythmia Screen.
AB  - Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer a
      novel in vitro platform for pre-clinical cardiotoxicity and pro-arrhythmia
      screening of drugs in development. To date hiPSC-CMs used for cardiotoxicity
      testing display an immature, fetal-like cardiomyocyte structural and
      electrophysiological phenotype which has called into question the applicability
      of hiPSC-CM findings to the adult heart. The aim of the current work was to
      determine the effect of cardiomyocyte maturation state on hiPSC-CM drug
      responsiveness. To this end, here we developed a high content pro-arrhythmia
      screening platform consisting of either fetal-like or mature hiPSC-CM monolayers.
      Compounds tested in the screen were selected based on the pro-arrhythmia risk
      classification (Low risk, Intermediate risk, or High risk) established recently
      by the FDA and major stakeholders in the Drug Discovery field for the validation
      of the Comprehensive In vitro Pro-Arrhythmia Assay (CiPA). Here we show that
      maturation state of hiPSC-CMs determines the absolute pro-arrhythmia risk score
      calculated for these compounds. Thus, the maturation state of hiPSC-CMs should be
      considered prior to pro-arrhythmia and cardiotoxicity screening in drug discovery
      programs.

PMID- 29061981
TI  - Optogenetic Neuronal Silencing in Drosophila during Visual Processing.
AB  - Optogenetic channels and ion pumps have become indispensable tools in
      neuroscience to manipulate neuronal activity and thus to establish synaptic
      connectivity and behavioral causality. Inhibitory channels are particularly
      advantageous to explore signal processing in neural circuits since they permit
      the functional removal of selected neurons on a trial-by-trial basis. However,
      applying these tools to study the visual system poses a considerable challenge
      because the illumination required for their activation usually also stimulates
      photoreceptors substantially, precluding the simultaneous probing of visual
      responses. Here, we explore the utility of the recently discovered anion
      channelrhodopsins GtACR1 and GtACR2 for application in the visual system of
      Drosophila. We first characterized their properties using a larval crawling
      assay. We further obtained whole-cell recordings from cells expressing GtACR1,
      which mediated strong and light-sensitive photocurrents. Finally, using
      physiological recordings and a behavioral readout, we demonstrate that GtACR1
      enables the fast and reversible silencing of genetically targeted neurons within
      circuits engaged in visual processing.

PMID- 29061980
TI  - Structure of human lysosomal acid alpha-glucosidase-a guide for the treatment of
      Pompe disease.
AB  - Pompe disease, a rare lysosomal storage disease caused by deficiency of the
      lysosomal acid alpha-glucosidase (GAA), is characterized by glycogen
      accumulation, triggering severe secondary cellular damage and resulting in
      progressive motor handicap and premature death. Numerous disease-causing
      mutations in the gaa gene have been reported, but the structural effects of the
      pathological variants were unknown. Here we present the high-resolution crystal
      structures of recombinant human GAA (rhGAA), the standard care of Pompe disease.
      These structures portray the unbound form of rhGAA and complexes thereof with
      active site-directed inhibitors, providing insight into substrate recognition and
      the molecular framework for the rationalization of the deleterious effects of
      disease-causing mutations. Furthermore, we report the structure of rhGAA in
      complex with the allosteric pharmacological chaperone N-acetylcysteine, which
      reveals the stabilizing function of this chaperone at the structural level.

PMID- 29061982
TI  - The role of EZH2 in overall survival of colorectal cancer: a meta-analysis.
AB  - Enhancer of zeste homolog 2 (EZH2) is the catalitic subunit of polycomb
      repressive complex 2 and mediates gene silencing. EZH2 is overexpressed in many
      cancers and correlates with poor prognosis. The role of the gene EZH2 in
      colorectal cancer survival is uncertainly, the aim of this study is clear this
      relationship. Relevant literaure was searched from electronic databases. A meta
      analysis was performed with elegible studies which quantitatively evaluated the
      relationship between EZH2 overexpression and survival of patients with colorectal
      cancer. Survival data were aggregated and quantitatively analyzed. We performed a
      meta-analysis of 8 studies (n = 1059 patients) that evaluated the correlation
      between EZH2 overexpression and survival in patients with colorectal cancer.
      Combined hazard ratios suggested that EZH2 overexpression was associated with
      better prognosis of overall survival (OS) HR(hazard ratio) = 0.61 95% CI (0.38
      0.84) We performed bias analysis according Egger and Begg,s test and we did not
      find publication bias. EZH2 overexpression indicates a better prognosis for
      colorectal cancer.

PMID- 29061984
TI  - Region and species dependent mechanical properties of adolescent and young adult
      brain tissue.
AB  - Traumatic brain injuries, the leading cause of death and disability in children
      and young adults, are the result of a rapid acceleration or impact of the head.
      In recent years, a global effort to better understand the biomechanics of TBI has
      been undertaken, with many laboratories creating detailed computational models of
      the head and brain. For these models to produce realistic results they require
      accurate regional constitutive data for brain tissue. However, there are large
      differences in the mechanical properties reported in the literature. These
      differences are likely due to experimental parameters such as specimen age, brain
      region, species, test protocols, and fiber direction which are often not
      reported. Furthermore, there is a dearth of reported viscoelastic properties for
      brain tissue at large-strain and high rates. Mouse, rat, and pig brains are
      impacted at 10/s to a strain of ~36% using a custom-built micro-indenter with a
      125 MUm radius. It is shown that the resultant mechanical properties are
      dependent on specimen-age, species, and region, under identical experimental
      parameters.

PMID- 29061983
TI  - Interplay of cis and trans mechanisms driving transcription factor binding and
      gene expression evolution.
AB  - Noncoding regulatory variants play a central role in the genetics of human
      diseases and in evolution. Here we measure allele-specific transcription factor
      binding occupancy of three liver-specific transcription factors between crosses
      of two inbred mouse strains to elucidate the regulatory mechanisms underlying
      transcription factor binding variations in mammals. Our results highlight the pre
      eminence of cis-acting variants on transcription factor occupancy divergence.
      Transcription factor binding differences linked to cis-acting variants generally
      exhibit additive inheritance, while those linked to trans-acting variants are
      most often dominantly inherited. Cis-acting variants lead to local coordination
      of transcription factor occupancies that decay with distance; distal coordination
      is also observed and may be modulated by long-range chromatin contacts. Our
      results reveal the regulatory mechanisms that interplay to drive transcription
      factor occupancy, chromatin state, and gene expression in complex mammalian cell
      states.

PMID- 29061985
TI  - Palaeobiology of red and white blood cell-like structures, collagen and
      cholesterol in an ichthyosaur bone.
AB  - Carbonate concretions are known to contain well-preserved fossils and soft
      tissues. Recently, biomolecules (e.g. cholesterol) and molecular fossils
      (biomarkers) were also discovered in a 380 million-year-old concretion, revealing
      their importance in exceptional preservation of biosignatures. Here, we used a
      range of microanalytical techniques, biomarkers and compound specific isotope
      analyses to report the presence of red and white blood cell-like structures as
      well as platelet-like structures, collagen and cholesterol in an ichthyosaur bone
      encapsulated in a carbonate concretion from the Early Jurassic (~182.7 Ma). The
      red blood cell-like structures are four to five times smaller than those
      identified in modern organisms. Transmission electron microscopy (TEM) analysis
      revealed that the red blood cell-like structures are organic in composition. We
      propose that the small size of the blood cell-like structures results from an
      evolutionary adaptation to the prolonged low oxygen atmospheric levels prevailing
      during the 70 Ma when ichthyosaurs thrived. The delta13C of the ichthyosaur bone
      cholesterol indicates that it largely derives from a higher level in the food
      chain and is consistent with a fish and cephalopod diet. The combined findings
      above demonstrate that carbonate concretions create isolated environments that
      promote exceptional preservation of fragile tissues and biomolecules.

PMID- 29061986
TI  - Relationships between different types of physical activity and metabolic syndrome
      among Taiwanese workers.
AB  - This study aimed to investigate the relationships between different types of
      physical activity (PA) and metabolic syndrome (MetS). In this cross-sectional
      study, 3,296 Taiwanese workers were enrolled. A self-reported questionnaire was
      used to assess nutritional health behavior and PA levels related to occupation,
      leisure time, and commuting. Anthropometric measures, blood pressure and
      biochemical determinations of the blood were also obtained. Multiple logistic
      regression was used to evaluate the adjusted odds ratios (ORs) and 95% confidence
      intervals (CI) of MetS and its components associated with different types of PA.
      The prevalence of MetS was 16.6% in workers. Compared with a low level of leisure
      time PA, a high level of leisure-time PA showed a significantly lower risk of
      high triglycerides (OR 0.73, 95% CI 0.61-0.87) and MetS (OR 0.76, 95% CI 0.62
      0.95). Compared with a low level of occupational PA, a high level of occupational
      PA represented a significantly lower risk of both abdominal adiposity (OR 0.64,
      95% CI 0.49-0.84) and high triglycerides (OR 0.71, 95% CI 0.55-0.90). However,
      commuting PA levels were not significantly associated with MetS and its
      components. In conclusion, occupational PA as well as leisure-time PA could be
      important for the prevention of MetS.

PMID- 29061987
TI  - Genetic Diversity and Phylogenetic Differentiation of Southwestern Chinese Han: a
      comprehensive and comparative analysis on 21 non-CODIS STRs.
AB  - Short tandem repeats (STRs), with high polymorphism and complex evolution
      information, play a significant role in genetic association studies like
      population genetics, molecular anthropology and human forensics. However, human
      genetic diversity has only been partially sampled and available for Southwest
      Chinese Han population, as well as the genetic architecture of this population
      remains uncharacterized. In this work, 368 unrelated Han individuals from Sichuan
      province were firstly genotyped with 21 non-CODIS autosomal STRs, and
      phylogenetic relationships along administrative (Han Chinese from different
      regions) and ethnic divisions (minority ethnic groups) were subsequently
      investigated. The CMP and CPE were 6.2796 * 10-20 and 0.9999999, respectively.
      Analysis of molecular variance (AMOVA), principal component analysis (PCA),
      multidimensional scaling plots (MDS) and phylogenetic analysis consistently
      demonstrated that the Southwest Han population had a close genetic relationship
      with the geographically close population (Hunan Han) and kept a distant genetic
      relationship with some ethnic groups, most prominently for Gansu Yugu and Fujian
      She. Furthermore, no significant genetic distinction between the Northern Han and
      Southern Han was observed. Aforementioned results suggested that these 21 STRs
      are highly polymorphic and informative, which are suitable for human
      identification and population genetics.

PMID- 29061988
TI  - Aquarius is required for proper CtIP expression and homologous recombination
      repair.
AB  - Accumulating evidence indicates that transcription is closely related to DNA
      damage formation and that the loss of RNA biogenesis factors causes genome
      instability. However, whether such factors are involved in DNA damage responses
      remains unclear. We focus here on the RNA helicase Aquarius (AQR), a known R-loop
      processing factor, and show that its depletion in human cells results in the
      accumulation of DNA damage during S phase, mediated by R-loop formation. We
      investigated the involvement of Aquarius in DNA damage responses and found that
      AQR knockdown decreased DNA damage-induced foci formation of Rad51 and
      replication protein A, suggesting that Aquarius contributes to homologous
      recombination (HR)-mediated repair of DNA double-strand breaks (DSBs).
      Interestingly, the protein level of CtIP, a DSB processing factor, was decreased
      in AQR-knockdown cells. Exogenous expression of Aquarius partially restored CtIP
      protein level; however, CtIP overproduction did not rescue defective HR in AQR
      knockdown cells. In accordance with these data, Aquarius depletion sensitized
      cells to genotoxic agents. We propose that Aquarius contributes to the
      maintenance of genomic stability via regulation of HR by CtIP-dependent and 
      independent pathways.

PMID- 29061989
TI  - Precision of a new ocular biometer in eyes with cataract using swept source
      optical coherence tomography combined with Placido-disk corneal topography.
AB  - The present study was to assess the precision (repeatability and reproducibility)
      of a new optical biometer (OA-2000, Tomey, Japan) based on swept-source optical
      coherence tomography (SS-OCT) and Placido disk topography in eyes with cataracts.
      Seventy-eight eyes from seventy-eight patients with cataracts were evaluated.
      Axial length (AL), anterior chamber depth (ACD), keratometry (K) over a 2.5 mm
      and 3.0 mm diameter, lens thickness (LT), central corneal thickness (CCT) and
      white-to-white (WTW) distance were measured by 2 skilled operators. OA-2000
      measurements were highly repeatable and reproducible for all parameters
      (intraclass correlation, 0.925 to 1.000). OA-2000 derived K-values with a
      diameter of 3.0mm showed narrower 95% limits of agreement (LoA) (SRK/T: -0.18 to
      0.16D; Holladay 1: -0.20 to 0.19D; Hoffer Q: -0.22 to 0.20D) than those with a
      diameter of 2.5 mm for IOL power calculations (SRK/T: -0.20 to 0.20D; Holladay 1:
      -0.23 to 0.23D; Hoffer Q: -0.25 to 0.25D). The precision (repeatability and
      reproducibility) of the OA-2000 was excellent for all parameters. The 3.0mm
      diameter K-readings appear to be the most reliable choice for calculation of IOL
      power with the OA-2000. In addition, the average values determined from each
      operator's 3 consecutive readings were more reproducible.

PMID- 29061990
TI  - TMAO is Associated with Mortality: Impact of Modestly Impaired Renal Function.
AB  - Trimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that is cleared
      by the kidney and linked to renal function. We explored the relationship between
      TMAO and all-cause mortality, and determined whether this association was
      modified by renal function. A prospective study was performed among PREVEND
      participants to examine associations of plasma TMAO with all-cause mortality.
      After median follow-up of 8.3 years in 5,469 participants, 322 subjects died.
      TMAO was positively associated with age, body mass index, type 2 diabetes
      mellitus and inversely with estimated glomerular filtration rate
      (eGFRcreatcysC)(all P < 0.001). Subjects in the highest versus lowest TMAO
      quartile had a crude 1.86-fold higher mortality risk (Ptrend < 0.001). After
      adjustment for several risk factors, TMAO remained associated with all-cause
      mortality [HR:1.36 (95% CI, 0.97-1.91),Ptrend = 0.016]. This association was lost
      after further adjustment for urinary albumin excretion and eGFR [HR:1.15 (95% CI,
      0.81-1.64),Ptrend = 0.22]. The association of TMAO with mortality was modified by
      eGFR in crude and age- and sex-adjusted analyses (interaction P = 0.002). When
      participants were stratified by renal function (eGFR < vs. >=90 mL/min/1.73 m2),
      TMAO was associated with all-cause mortality only in subjects with eGFR <90
      mL/min/1.73 m2 [adjusted HR:1.18 (95% CI, 1.02-1.36),P = 0.023]. In conclusion,
      TMAO is associated with all-cause mortality, particularly in subjects with eGFR
      <90 mL/min/1.73 m2.

PMID- 29061991
TI  - Mechanistic Insights into the Cholesterol-dependent Binding of Perfringolysin O
      based Probes and Cell Membranes.
AB  - Cholesterol distribution in the cell is maintained by both vesicular and non
      vesicular sterol transport. Non-vesicular transport is mediated by the
      interaction of membrane-embedded cholesterol and water-soluble proteins. Small
      changes to the lipid composition of the membrane that do not change the total
      cholesterol content, can significantly affect how cholesterol interacts with
      other molecules at the surface of the membrane. The cholesterol-dependent
      cytolysin Perfringolysin O (PFO) constitutes a powerful tool to detect
      cholesterol in membranes, and the use of PFO-based probes has flourished in
      recent years. By using a non-lytic PFO derivative, we showed that the sensitivity
      of the probes for cholesterol can be tuned by modifications introduced directly
      in the membrane-interacting loops and/or by modifying residues away from the
      membrane-interacting domain. Through the use of these biosensors on live RAW
      264.7 cells, we found that changes in the overall cholesterol content have a
      limited effect on the average cholesterol accessibility at the surface of the
      membrane. We showed that these exquisite biosensors report on changes in
      cholesterol reactivity at the membrane surface independently of the overall
      cholesterol content in the membrane.

PMID- 29061992
TI  - Correlating Fluorescence and High-Resolution Scanning Electron Microscopy (HRSEM)
      for the study of GABAA receptor clustering induced by inhibitory synaptic
      plasticity.
AB  - Both excitatory and inhibitory synaptic contacts display activity dependent
      dynamic changes in their efficacy that are globally termed synaptic plasticity.
      Although the molecular mechanisms underlying glutamatergic synaptic plasticity
      have been extensively investigated and described, those responsible for
      inhibitory synaptic plasticity are only beginning to be unveiled. In this
      framework, the ultrastructural changes of the inhibitory synapses during
      plasticity have been poorly investigated. Here we combined confocal fluorescence
      microscopy (CFM) with high resolution scanning electron microscopy (HRSEM) to
      characterize the fine structural rearrangements of post-synaptic GABAA Receptors
      (GABAARs) at the nanometric scale during the induction of inhibitory long-term
      potentiation (iLTP). Additional electron tomography (ET) experiments on
      immunolabelled hippocampal neurons allowed the visualization of synaptic contacts
      and confirmed the reorganization of post-synaptic GABAAR clusters in response to
      chemical iLTP inducing protocol. Altogether, these approaches revealed that,
      following the induction of inhibitory synaptic potentiation, GABAAR clusters
      increase in size and number at the post-synaptic membrane with no other major
      structural changes of the pre- and post-synaptic elements.

PMID- 29061993
TI  - Live cell X-ray imaging of autophagic vacuoles formation and chromatin dynamics
      in fission yeast.
AB  - Seeing physiological processes at the nanoscale in living organisms without
      labeling is an ultimate goal in life sciences. Using X-ray ptychography, we
      explored in situ the dynamics of unstained, living fission yeast
      Schizosaccharomyces pombe cells in natural, aqueous environment at the nanoscale.
      In contrast to previous X-ray imaging studies on biological matter, in this work
      the eukaryotic cells were alive even after several ptychographic X-ray scans,
      which allowed us to visualize the chromatin motion as well as the autophagic cell
      death induced by the ionizing radiation. The accumulated radiation of the
      sequential scans allowed for the determination of a characteristic dose of
      autophagic vacuole formation and the lethal dose for fission yeast. The presented
      results demonstrate a practical method that opens another way of looking at
      living biological specimens and processes in a time-resolved label-free setting.

PMID- 29061994
TI  - A three-membered ring approach to carbonyl olefination.
AB  - The carbon-carbon double bond, with its diverse and multifaceted reactivity,
      occupies a prominent position in organic synthesis. Although a variety of simple
      alkenes are readily available, the mild and chemoselective introduction of a unit
      of unsaturation into a functionalized organic molecule remains an ongoing area of
      research, and the olefination of carbonyl compounds is a cornerstone of such
      approaches. Here we show the direct olefination of hydrazones via the
      intermediacy of three-membered ring species generated by addition of sulfoxonium
      ylides, departing from the general dogma of alkenes synthesis from carbonyls.
      Moreover, the mild reaction conditions and operational simplicity of the
      transformation render the methodology appealing from a practical point of view.

PMID- 29061995
TI  - CCN3 is a therapeutic target relating enhanced stemness and coagulation in
      hepatocellular carcinoma.
AB  - The general prognosis of patients with hepatocellular carcinoma (HCC) remains
      extremely dismal, due to the high frequency of metastasis. Since 2003, our
      research group has explored the gene expression profiles of metastasized HCC
      tissue samples and identified a significant upregulation of CCN3. However, the
      role and precise pathological function of CCN3 remains elusive. We showed that
      CCN3 is associated with the poor prognosis of patients with HCC, the malignant
      phenotype of HCC, and vascular thrombosis. We further evaluated the negative
      roles of CCN3 in vitro and in vivo, and identified osteopontin (OPN), and
      coagulation factors tissue factor (TF) and thrombin as the leading genes
      downstream of CCN3, that are positively associated with HCC cell stemness. We
      demonstrated that overexpressed CCN3 in HCC cells leads to enhanced survival and
      increased number of pulmonary metastases in vivo. The elevated levels of OPN and
      TF were associated with signal activation of nuclear factor kappaB (NFkappaB) and
      extracellular signal-regulated kinases (ERK). Our findings suggest CCN3 is a
      potential therapeutic target that would affect the upregulation of OPN and
      coagulation factors, which would lead to an enhanced stemness and blood
      coagulation microenvironment in HCC tissue.

PMID- 29061996
TI  - Site-selective spectroscopy with depth resolution using resonant x-ray
      reflectometry.
AB  - Combining dissimilar transition metal oxides (TMOs) into artificial
      heterostructures enables to create electronic interface systems with new
      electronic properties that do not exist in bulk. A detailed understanding of how
      such interfaces can be used to tailor physical properties requires
      characterization techniques capable to yield interface sensitive spectroscopic
      information with monolayer resolution. In this regard resonant x-ray reflectivity
      (RXR) provides a unique experimental tool to achieve exactly this. It yields the
      element specific electronic depth profiles in a non-destructive manner. Here,
      using a YBa2Cu3O7-delta (YBCO) thin film, we demonstrate that RXR is further
      capable to deliver site selectivity. By applying a new analysis scheme to RXR,
      which takes the atomic structure of the material into account, together with
      information of the local charge anisotropy of the resonant ions, we obtained
      spectroscopic information from the different Cu sites (e.g., chain and plane)
      throughout the film profile. While most of the film behaves bulk-like, we observe
      that the Cu-chains at the surface show characteristics of electron doping,
      whereas the Cu-planes closest to the surface exhibit an orbital reconstruction
      similar to that observed at La1-x Ca x MnO3/YBCO interfaces.

PMID- 29061997
TI  - Improved detection of BRAF V600E using allele-specific PCR coupled with external
      and internal controllers.
AB  - Although traditional allele-specific PCR (tAS-PCR) is a common screening method
      for BRAF V600E mutations, its lower amplification specificity and mutation
      selectivity have limited its clinical applications. We hypothesize that these
      limitations are associated with the weaker specificities of allele-specific
      primers and the thermodynamic driving forces of DNA polymerase. We used three
      strategies to circumvent these limitations, namely, modifying allele-specific
      primers, introducing a competitive external allele-specific controller (i.e., cAS
      PCR), and introducing a referenced internal positive controller in the cAS-PCR
      (i.e., rcAS-PCR). The amplification sensitivities and specificities were
      influenced by the position of the artificially introduced mismatched nucleotide
      in the allele-specific primers. Moreover, both cAS-PCR and rcAS-PCR could detect
      single-copy BRAF V600E alleles with higher mutation selectivity (0.1%) than tAS
      PCR. In addition, cAS-PCR eliminated false-negative results caused by various PCR
      inhibitors that might be present in the DNA solutions. The rcAS-PCR could also be
      employed to avoid the false-negative results caused by low-abundance input
      templates in cAS-PCR. In conclusion, rcAS-PCR provides a rapid, simple, and low
      cost method for detecting low levels of the mutated BRAF V600E gene.

PMID- 29061998
TI  - Deciphering pore-level precipitation mechanisms.
AB  - Mineral precipitation and dissolution in aqueous solutions has a significant
      effect on solute transport and structural properties of porous media. The
      understanding of the involved physical mechanisms, which cover a large range of
      spatial and temporal scales, plays a key role in several geochemical and
      industrial processes. Here, by coupling pore scale reactive transport simulations
      with classical nucleation theory, we demonstrate how the interplay between
      homogeneous and heterogeneous precipitation kinetics along with the non-linear
      dependence on solute concentration affects the evolution of the system. Such
      phenomena are usually neglected in pure macroscopic modelling. Comprehensive
      parametric analysis and comparison with laboratory experiments confirm that
      incorporation of detailed microscale physical processes in the models is
      compulsory. This sheds light on the inherent coupling mechanisms and bridges the
      gap between atomistic processes and macroscopic observations.

PMID- 29061999
TI  - A single extracellular amino acid in Free Fatty Acid Receptor 2 defines
      antagonist species selectivity and G protein selection bias.
AB  - Free Fatty Acid Receptor 2 is a GPCR activated by short chain fatty acids
      produced in high levels in the lower gut by microbial fermentation of non
      digestible carbohydrates. A major challenge in studying this receptor is that the
      mouse ortholog does not have significant affinity for antagonists that are able
      to block the human receptor. Docking of exemplar antagonists from two chemical
      series to homology models of both human and mouse Free Fatty Acid Receptor 2
      suggested that a single lysine - arginine variation at the extracellular face of
      the receptor might provide the basis for antagonist selectivity and mutational
      swap studies confirmed this hypothesis. Extending these studies to agonist
      function indicated that although the lysine - arginine variation between human
      and mouse orthologs had limited effect on G protein-mediated signal transduction,
      removal of positive charge from this residue produced a signalling-biased variant
      of Free Fatty Acid Receptor 2 in which Gi-mediated signalling by both short chain
      fatty acids and synthetic agonists was maintained whilst there was marked loss of
      agonist potency for signalling via Gq/11 and G12/13 G proteins. A single residue
      at the extracellular face of the receptor thus plays key roles in both agonist
      and antagonist function.

PMID- 29062000
TI  - FTY720-induced endocytosis of yeast and human amino acid transporters is preceded
      by reduction of their inherent activity and TORC1 inhibition.
AB  - FTY720 is a sphingoid base analog that acts as an anticancer agent in animal
      models. Its effect on tumor cells stems largely from its ability to trigger
      endocytosis of several nutrient transporters. The observation that FTY720
      similarly stimulates downregulation of amino acid permeases in yeast suggests
      that the cellular mechanisms it targets, which are still poorly characterized,
      are evolutionarily conserved. We here report that adding FTY720 to yeast cells
      results in rapid inhibition of the intrinsic activity of multiple permeases. This
      effect is associated with inhibition of the TORC1 kinase complex, which in turn
      promotes ubiquitin-dependent permease endocytosis. Further analysis of the Gap1
      permease showed that FTY720 elicits its ubiquitylation via the same factors that
      promote this modification when TORC1 is inhibited by rapamycin. We also show that
      FTY720 promotes endocytosis of the LAT1/SLC7A5 amino acid transporter in HeLa
      cells, this being preceded by loss of its transport activity and by mTORC1
      inhibition. Our data suggest that in yeast, TORC1 deactivation resulting from
      FTY720-mediated inhibition of membrane transport elicits permease endocytosis.
      The same process seems to occur in human cells even though our data and previous
      reports suggest that FTY720 promotes transporter endocytosis via an additional
      mechanism insensitive to rapamycin.

PMID- 29062001
TI  - Combined TDDFT and AIM Insights into Photoinduced Excited State Intramolecular
      Proton Transfer (ESIPT) Mechanism in Hydroxyl- and Amino-Anthraquinone Solution.
AB  - Time-dependent density functional theory (TDDFT) and atoms in molecules (AIM)
      theory are combined to study the photoinduced excited state intramolecular proton
      transfer (ESIPT) dynamics for eight anthraquinones (AQs) derivatives in solution.
      The calculated absorption and emission spectra are consistent with the available
      experimental data, verifying the suitability of the theory selected. The systems
      with the excited-state exothermic proton transfer, such as 1-HAQ, 1,5-DHAQ and
      TFAQ, emit completely from transfer structure (T), while the reactions for those
      without ESIPT including 1,4-DHAQ and AAAQ appear to be endothermic. Three
      reaction properties of three systems (1,8-DHAQ, DCAQ and CAAQ) are between the
      exothermic and endothermic, sensitive to the solvent. Energy scanning shows that
      1,4-DHAQ and AAAQ exhibit the higher ESIPT energy barriers compared to 1-HAQ, 1,5
      DHAQ and TFAQ with the "barrierless" ESIPT process. The ESIPT process is
      facilitated by the strengthening of hydrogen bonds in excited state. With AIM
      theory, it is observed that the change in electrons density rho(r) and potential
      energy density V(r) at BCP position between ground state and excited state are
      crucial factors to quantitatively elucidate the ESIPT.

PMID- 29062002
TI  - The space of genotypes is a network of networks: implications for evolutionary
      and extinction dynamics.
AB  - The forcing that environmental variation exerts on populations causes continuous
      changes with only two possible evolutionary outcomes: adaptation or extinction.
      Here we address this topic by studying the transient dynamics of populations on
      complex fitness landscapes. There are three important features of realistic
      landscapes of relevance in the evolutionary process: fitness landscapes are rough
      but correlated, their fitness values depend on the current environment, and many
      (often most) genotypes do not yield viable phenotypes. We capture these
      properties by defining time-varying, holey, NK fitness landscapes. We show that
      the structure of the space of genotypes so generated is that of a network of
      networks: in a sufficiently holey landscape, populations are temporarily stuck in
      local networks of genotypes. Sudden jumps to neighbouring networks through narrow
      adaptive pathways (connector links) are possible, though strong enough local
      trapping may also cause decays in population growth and eventual extinction. A
      combination of analytical and numerical techniques to characterize complex
      networks and population dynamics on such networks permits to derive several
      quantitative relationships between the topology of the space of genotypes and the
      fate of evolving populations.

PMID- 29062003
TI  - Maternal Glucocorticoid Elevation and Associated Fetal Thymocyte Apoptosis are
      Involved in Immune Disorders of Prenatal Caffeine Exposed Offspring Mice.
AB  - Our previous study showed that prenatal caffeine exposure (PCE) could induce
      intrauterine growth retardation (IUGR) and glucocorticoid elevation in the fetus.
      Researchers suggested that IUGR is a risk factor for T helper cell (Th)1/Th2
      deviation. However, whether PCE can induce these immune disorders and the
      underlying mechanisms of that induction remain unknown. This study aimed to
      observe the effects of PCE on the Th1/Th2 balance in offspring and further
      explore the developmental origin mechanisms from the perspective of
      glucocorticoid overexposure-induced thymocyte apoptosis. An IUGR model was
      established by caffeine administration from gestational day (GD) 9 to GD 18, and
      the offspring were immunized on postnatal day (PND) 42. The results show that
      maternal glucocorticoid overexposure increased fetal thymocyte apoptosis by
      activating both the Fas-mediated and the Bim-regulated apoptotic pathways. After
      birth, accelerated thymocyte apoptosis and Th1 suppression were also found in the
      PCE offspring at PND 14 and PND 49. Moreover, the PCE offspring showed immune
      disorders after immunization, manifesting as increased IgG1/IgG2a ratio and IL-4
      production in the serum. In conclusion, PCE could induce fetal overexposure to
      maternal glucocorticoids and increase thymocyte apoptosis, which could persist
      into postnatal life and be implicated in Th1 inhibition and further immune
      disorders.

PMID- 29062005
TI  - Bone Marrow Mononuclear Cells Combined with Beta-Tricalcium Phosphate Granules
      for Alveolar Cleft Repair: A 12-Month Clinical Study.
AB  - Alveolar cleft is the most common congenital bone defect. Autologous iliac crest
      bone graft (ICBG) is the most widely adopted procedure for alveolar cleft repair,
      but the condition is associated with door-site morbidities. For the first time,
      this study used bone marrow mononuclear cells (BMMNCs) combined with beta
      tricalcium phosphate (beta-TCP) granules to repair alveolar bone defect. The
      effectiveness of this technique was compared with autologous ICBG after 12 months
      of follow-up. The bone formation volume was quantitatively evaluated by three
      dimensional computed tomography and computer aided engineering technology.
      BMMNCs/beta-TCP granule grafting was radiographically equivalent to ICBG in
      alveolar cleft repair. Although considerable resorption was observed up to 6
      months after surgery, no significant differences were noted in the Chelsea score
      and bone formation volume between groups. These finding indicate that BMMNCs/beta
      TCP grafting is a safe and effective approach for alveolar bone regeneration.

PMID- 29062006
TI  - Thermally stable amorphous tantalum yttrium oxide with low IR absorption for
      magnetophotonic devices.
AB  - Thin film oxide materials often require thermal treatment at high temperature
      during their preparation, which can limit them from being integrated in a range
      of microelectronic or optical devices and applications. For instance, it has been
      a challenge to retain the optical properties of Bragg mirrors in optical systems
      at temperatures above 700  degrees C because of changes in the crystalline
      structure of the high-refractive-index component. In this study, a ~100 nm-thick
      amorphous film of tantalum oxide and yttrium oxide with an yttrium-to-tantalum
      atomic fraction of 14% was prepared by magnetron sputtering. The film
      demonstrated high resistance to annealing above 850  degrees C without
      degradation of its optical properties. The electronic and crystalline structures,
      stoichiometry, optical properties, and integration with magnetooptical materials
      are discussed. The film was incorporated into Bragg mirrors used with iron garnet
      microcavities, and it contributed to an order-of-magnitude enhancement of the
      magnetooptical figure of merit at near-infrared wavelengths.

PMID- 29062004
TI  - Ethanol Induces Enhanced Vascularization Bioactivity of Endothelial Cell-Derived
      Extracellular Vesicles via Regulation of MicroRNAs and Long Non-Coding RNAs.
AB  - Extracellular vesicles (EVs), such as exosomes, have been identified as
      regulators of vascular remodeling and have promise as therapeutics for
      vascularization applications. Towards development of EVs as therapeutics, it has
      been demonstrated that physiological stimuli of angiogenic phenotypes in EV
      producing cells can enhance the potency of EVs for vascularization. The goal of
      this study was to assess whether ethanol, which induces angiogenic phenotypes in
      endothelial cells, could be employed to enhance endothelial-derived EV
      vascularization bioactivity. The results indicate that ethanol conditioning of
      endothelial cells increases the ability of endothelial EVs to induce a pro
      vascularization response. This response is due in part to increased CD34
      expression in recipient endothelial cells that may result from downregulation of
      microRNA-106b in EVs isolated from ethanol-conditioned producer endothelial
      cells. Further, ethanol-induced upregulation of long non-coding RNAs (lncRNAs)
      HOTAIR and MALAT1 in endothelial EVs was observed to play a significant role in
      mediating pro-angiogenic effects of these vesicles. Overall, these studies
      validate ethanol conditioning as a method to enhance the bioactivity of
      endothelial EVs via regulation of EV-associated microRNAs (miRNAs) and,
      especially, lncRNAs. Further, the results suggest that alcohol consumption may
      activate endothelial EVs towards a pro-vascularization phenotype, which could
      have implications for alcohol-induced tumor angiogenesis.

PMID- 29062008
TI  - Zero-dc-field rotation-direction-dependent magnetization switching induced by a
      circularly polarized microwave magnetic field.
AB  - Magnetization switching of high-anisotropy nanomagnets by a small magnetic field
      is a key challenge in developing future magnetic nanodevices. In this paper, we
      experimentally demonstrate magnetization switching of a perpendicularly
      magnetized nanomagnet induced solely by an in-plane circularly polarized
      microwave magnetic field. Applying a microwave field with an amplitude below 5%
      of the anisotropy field induces large ferromagnetic resonance excitation, which
      results in magnetization switching even in the absence of a dc field. This kind
      of magnetization switching is induced by a microwave field with a duration of 0.5
      ns and is clearly dependent on the rotation direction of the microwave field.

PMID- 29062007
TI  - Dimethyl pyrazol-based nitrification inhibitors effect on nitrifying and
      denitrifying bacteria to mitigate N2O emission.
AB  - Nitrous oxide (N2O) emissions have been increasing as a result of intensive
      nitrogen (N) fertilisation. Soil nitrification and denitrification are the main
      sources of N2O, and the use of ammonium-based fertilisers combined with
      nitrification inhibitors (NIs) could be useful in mitigating N2O emissions from
      agricultural systems. In this work we looked at the N2O mitigation capacity of
      two dimethylpyrazol-based NIs, 3,4-dimethylpyrazole phosphate (DMPP) and 2-(N-3,4
      dimethyl-1H-pyrazol-1-yl) succinic acid isomeric mixture (DMPSA), on soil
      nitrifying and denitrifying microbial populations under two contrasting soil
      water contents (40% and 80% soil water filled pore space; WFPS). Our results show
      that DMPP and DMPSA are equally efficient at reducing N2O emissions under 40%
      WFPS conditions by inhibiting bacterial ammonia oxidation. In contrast, at 80%
      WFPS DMPSA was less efficient than DMPP at reducing N2O emissions. Interestingly,
      at 80% WFPS, where lowered oxygen availability limits nitrification, both DMPP
      and DMPSA not only inhibited nitrification but also stimulated N2O reduction to
      molecular nitrogen (N2) via nitrous oxide reductase activity (Nos activity).
      Therefore, in this work we observed that DMP-based NIs stimulated the reduction
      of N2O to N2 by nitrous oxide reductase during the denitrification process.

PMID- 29062009
TI  - Comparison of four automated microbiology systems with 16S rRNA gene sequencing
      for identification of Chryseobacterium and Elizabethkingia species.
AB  - Chryseobacterium and Elizabethkingia species have recently emerged as causative
      agents in life-threatening infections in humans. We aimed to evaluate the rates
      at which four common microbial identification systems identify Chryseobacterium
      and Elizabethkingia species in clinical microbiology laboratories. Based on the
      results of 16S rRNA gene sequencing, a total of 114 consecutive bacteremic
      isolates, including 36 (31.6%) C. indologenes, 35 (30.7%) E. anophelis, 22
      (19.3%) C. gleum, 13 (11.4%) E. meningoseptica, and other species, were included
      in this study. The overall concordance between each method and 16S rRNA gene
      sequencing when identifying Chryseobacterium and Elizabethkingia species was
      42.1% for API/ID32, 41.2% for Phoenix 100 ID/AST, 43.9% for VITEK 2, and 42.1%
      for VITEK MS. Among the 22 C. gleum isolates, only one (4.8%) was correctly
      identified using VITEK 2 and Phoenix 100 ID/AST, and none were accurately
      recognized using API/ID32 or VITEK MS. Except for two isolates that were not
      identified using API/ID32, all E. anophelis isolates were misidentified by all
      four identification systems as E. meningoseptica. Our results show that these
      approaches have low accuracy when identifying Chryseobacterium and
      Elizabethkingia species. Hence, we recommend amending the discrimination rate of
      and adding non-claimed pathogens to databases of microbial identification
      systems.

PMID- 29062010
TI  - An automated method for identifying an independent component analysis-based
      language-related resting-state network in brain tumor subjects for surgical
      planning.
AB  - As a noninvasive and "task-free" technique, resting-state functional magnetic
      resonance imaging (rs-fMRI) has been gradually applied to pre-surgical functional
      mapping. Independent component analysis (ICA)-based mapping has shown advantage,
      as no a priori information is required. We developed an automated method for
      identifying language network in brain tumor subjects using ICA on rs-fMRI. In
      addition to standard processing strategies, we applied a discriminability-index
      based component identification algorithm to identify language networks in three
      different groups. The results from the training group were validated in an
      independent group of healthy human subjects. For the testing group, ICA and seed
      based correlation were separately computed and the detected language networks
      were assessed by intra-operative stimulation mapping to verify reliability of
      application in the clinical setting. Individualized language network mapping
      could be automatically achieved for all subjects from the two healthy groups
      except one (19/20, success rate = 95.0%). In the testing group (brain tumor
      patients), the sensitivity of the language mapping result was 60.9%, which
      increased to 87.0% (superior to that of conventional seed-based correlation
      [47.8%]) after extending to a radius of 1 cm. We established an automatic and
      practical component identification method for rs-fMRI-based pre-surgical mapping
      and successfully applied it to brain tumor patients.

PMID- 29062011
TI  - Improved emission of SiV diamond color centers embedded into concave plasmonic
      core-shell nanoresonators.
AB  - Configuration of three different concave silver core-shell nanoresonators was
      numerically optimized to enhance the excitation and emission of embedded silicon
      vacancy (SiV) diamond color centers simultaneously. Conditional optimization was
      performed to ensure ~20-30-40 and 50% apparent quantum efficiency (cQE) of SiV
      color centers. The enhancement spectra, as well as the near-field and charge
      distribution were inspected to uncover the underlying nanophotonical phenomena.
      The conditionally optimized coupled systems were qualified by the product of the
      radiative rate enhancements at the excitation and emission, which is nominated as
      P x factor. The optimized spherical core-shell nanoresonator containing a
      centralized emitter is capable of enhancing the emission considerably via bonding
      dipolar resonance. The P x factor is 529-fold with 49.7% cQE at the emission.
      Decentralization of the emitter leads to appearance of higher order nonradiative
      multipolar modes. Transversal and longitudinal dipolar resonance of the optimized
      ellipsoidal core-shell resonator was tuned to the excitation and emission, which
      results in 6.2?105 P x factor with 50.6% cQE at the emission. Rod-shaped concave
      core-shell nanoresonators exploit similar transversal and longitudinal dipolar
      resonance, moreover they enhance the fluorescence more significantly due to their
      antenna-like geometry. P x factor indicating 8.34?105 enhancement is achievable
      while the cQE is 50.3% at the emission.

PMID- 29062012
TI  - Microsphere Assisted Super-resolution Optical Imaging of Plasmonic Interaction
      between Gold Nanoparticles.
AB  - Conventional far-field microscopy cannot directly resolve the sub-diffraction
      spatial distribution of localized surface plasmons in metal nanostructures. Using
      BaTiO3 microspheres as far-field superlenses by collecting the near-field signal,
      we can map the origin of enhanced two-photon photoluminescence signal from the
      gap region of gold nanosphere dimers and gold nanorod dimers beyond the
      diffraction limit, on a conventional far-field microscope. As the angle theta
      between dimer's structural axis and laser polarisation changes, photoluminescence
      intensity varies with a cos4theta function, which agrees quantitatively with
      numerical simulations. An optical resolution of about lambda/7 (lambda: two
      photon luminescence central wavelength) is demonstrated at dimer's gap region.

PMID- 29062014
TI  - Endogenous physical regulation of population density in the freshwater protozoan
      Paramecium caudatum.
AB  - Studies confirm physical long-range cell-cell communication, most evidently based
      on electromagnetic fields. Effects concern induction or inhibition of cell
      growth. Their natural function is unclear. With the protozoan Paramecium caudatum
      I tested whether the signals regulate cell density and are electromagnetic. Up to
      300 cells/mL, cell growth in clones of this study is decreasingly pronounced.
      Using cuvettes as chemical barriers enabling physical communication  I  placed 5
      indicator cells/mL, the inducer populations, into smaller cuvettes that stand in
      bigger and contained 50, 100, 200 or 300 cells/mL. Under conditions of total
      darkness such pairs were mutually exposed for 48 hours. The hypothesis was that
      indicator cells, too, grow less the more neighbor cells there are. The bigger
      inducer populations were in the beginning the less they grew. The indicator
      populations grew accordingly; the more cells they were surrounded by the less
      they grew. The suppressing neighbors-effect disappeared when inner cuvettes were
      shielded by graphite known to shield electromagnetic radiation from GHz to PHz,
      i.e. to absorb energy from microwaves to light. These are the first results
      demonstrating non-contact physical quorum sensing for cell population density
      regulation. I assume rules intrinsic to electromagnetic fields interacting with
      matter and life.

PMID- 29062013
TI  - Near-simultaneous intravital microscopy of glucose uptake and mitochondrial
      membrane potential, key endpoints that reflect major metabolic axes in cancer.
AB  - While the demand for metabolic imaging has increased in recent years,
      simultaneous in vivo measurement of multiple metabolic endpoints remains
      challenging. Here we report on a novel technique that provides in vivo high
      resolution simultaneous imaging of glucose uptake and mitochondrial metabolism
      within a dynamic tissue microenvironment. Two indicators were leveraged; 2-[N-(7
      nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) reports on
      glucose uptake and Tetramethylrhodamine ethyl ester (TMRE) reports on
      mitochondrial membrane potential. Although we demonstrated that there was neither
      optical nor chemical crosstalk between 2-NBDG and TMRE, TMRE uptake was
      significantly inhibited by simultaneous injection with 2-NBDG in vivo. A
      staggered delivery scheme of the two agents (TMRE injection was followed by 2
      NBDG injection after a 10-minute delay) permitted near-simultaneous in vivo
      microscopy of 2-NBDG and TMRE at the same tissue site by mitigating the
      interference of 2-NBDG with normal glucose usage. The staggered delivery strategy
      was evaluated under both normoxic and hypoxic conditions in normal tissues as
      well as in a murine breast cancer model. The results were consistent with those
      expected for independent imaging of 2-NBDG and TMRE. This optical imaging
      technique allows for monitoring of key metabolic endpoints with the unique
      benefit of repeated, non-destructive imaging within an intact microenvironment.

PMID- 29062015
TI  - Stimulation of synapse formation between stem cell-derived neurons and native
      brainstem auditory neurons.
AB  - Integration of stem cell-derived cells into native cellular environment remains a
      challenge in the field. This study developed novel methods to co-culture neural
      stem cell-derived spiral ganglion-like neurons (ScNs) and mouse auditory cochlear
      nucleus (CN) neurons to understand whether ScNs of the peripheral nervous system
      (PNS) synapse with CN neurons of the central nervous system (CNS). ScNs were
      obtained from neural stem cells that were derived from transgenic mouse pre
      labeled with enhanced green fluorescent protein (EGFP), whereas CN neurons were
      from postnatal mouse primary cultures. ScNs and CN neurons were co-cultured  for
      4-6 days in the absence or presence of astrocyte-conditioned medium (ACM). Class
      III beta-tubulin (TUJ1)-expressing connections were found between ScNs and CN
      neurons. Expression of the synaptic vesicle marker SV2 was significantly
      increased along connections between ScNs and CN neurons in the presence of ACM.
      Immunodepletion and knockout studies indicated that thrombospodin-1 played an
      important role in ACM-exerted synaptogenic effects. Newly-generated synapse-like
      structures expressed glutamatergic marker VGluT1, pre- and post-synaptic
      proteins. Synaptic vesicle recycling studies suggested functional synaptic
      vesicle retrieval. These results reveal that stem cell-derived PNS neurons are
      able to form functional connections with native CNS neurons, which is critical
      for stem cell-based neural pathway regeneration.

PMID- 29062016
TI  - Piezo-generated charge mapping revealed through direct piezoelectric force
      microscopy.
AB  - While piezoelectric and ferroelectric materials play a key role in many everyday
      applications, there are still a number of open questions related to their
      physics. To enhance our understanding of piezoelectrics and ferroelectrics,
      nanoscale characterization is essential. Here, we develop an atomic force
      microscopy based mode that obtains a direct quantitative analysis of the
      piezoelectric coefficient d33. We report nanoscale images of piezogenerated
      charge in a thick single crystal of periodically poled lithium niobate (PPLN), a
      bismuth ferrite (BiFO3) thin film, and lead zirconate titanate (PZT) by applying
      a force and recording the current produced by these materials. The quantification
      of d33 coefficients for PPLN (14 +/- 3 pC per N) and BFO (43 +/- 6 pC per N) is
      in agreement with the values reported in the literature. Even stronger evidence
      of the reliability of the method is provided by an equally accurate measurement
      of the significantly larger d33 of PZT.

PMID- 29062017
TI  - Comparing crop rotations between organic and conventional farming.
AB  - Cropland use activities are major drivers of global environmental changes and of
      farming system resilience. Rotating crops is a critical land-use driver, and a
      farmers' key strategy to control environmental stresses and crop performances.
      Evidence has accumulated that crop rotations have been dramatically simplified
      over the last 50 years. In contrast, organic farming stands as an alternative
      production way that promotes crop diversification. However, our understanding of
      crop rotations is surprisingly limited. In order to understand if organic farming
      would result in more diversified and multifunctional landscapes, we provide here
      a novel, systematic comparison of organic-to-conventional crop rotations at the
      global scale based on a meta-analysis of the scientific literature, paired with
      an independent analysis of organic-to-conventional land-use. We show that organic
      farming leads to differences in land-use compared to conventional: overall, crop
      rotations are 15% longer and result in higher diversity and evener crop species
      distribution. These changes are driven by a higher abundance of temporary
      fodders, catch and cover-crops, mostly to the detriment of cereals. We also
      highlighted differences in organic rotations between Europe and North-America,
      two leading regions for organic production. This increased complexity of organic
      crop rotations is likely to enhance ecosystem service provisioning to
      agroecosystems.

PMID- 29062020
TI  - Correspondence regarding two recent publications in npj:schizophrenia about DNAm
      and accelerated aging in schizophrenia.

PMID- 29062018
TI  - IFN-gamma and TNF-alpha synergism may provide a link between psoriasis and
      inflammatory atherogenesis.
AB  - Chronic inflammation is a critical component of atherogenesis, however, reliable
      human translational models aimed at characterizing these mechanisms are lacking.
      Psoriasis, a chronic inflammatory skin disease associated with increased
      susceptibility to atherosclerosis, provides a clinical human model that can be
      utilized to investigate the links between chronic inflammation and
      atherosclerosis development. We sought to investigate key biological processes in
      psoriasis skin and human vascular tissue to identify biological components that
      may promote atherosclerosis in chronic inflammatory conditions. Using a
      bioinformatics approach of human skin and vascular tissue, we determined IFN
      gamma and TNF-alpha are the dominant pro-inflammatory signals linking
      atherosclerosis and psoriasis. We then stimulated primary aortic endothelial
      cells and ex-vivo atherosclerotic tissue with IFN-gamma and TNF-alpha and found
      they synergistically increased monocyte and T-cell chemoattractants, expression
      of adhesion molecules on the endothelial cell surface, and decreased endothelial
      barrier integrity in vitro, therefore increasing permeability. Our data provide
      strong evidence of synergism between IFN-gamma and TNF- alpha in inflammatory
      atherogenesis and provide rationale for dual cytokine antagonism in future
      studies.

PMID- 29062019
TI  - Myoelectric Pattern Recognition Outperforms Direct Control for Transhumeral
      Amputees with Targeted Muscle Reinnervation: A Randomized Clinical Trial.
AB  - Recently commercialized powered prosthetic arm systems hold great potential in
      restoring function for people with upper-limb loss. However, effective use of
      such devices remains limited by conventional (direct) control methods, which rely
      on electromyographic signals produced from a limited set of muscles. Targeted
      Muscle Reinnervation (TMR) is a nerve transfer procedure that creates additional
      recording sites for myoelectric prosthesis control. The effects of TMR may be
      enhanced when paired with pattern recognition technology. We sought to compare
      pattern recognition and direct control in eight transhumeral amputees who had TMR
      in a balanced randomized cross-over study. Subjects performed a 6-8 week home
      trial using direct and pattern recognition control with a custom prostheses made
      from commercially available parts. Subjects showed statistically better
      performance in the Southampton Hand Assessment Procedure (p = 0.04) and the
      Clothespin relocation task (p = 0.02). Notably, these tests required movements
      along 3 degrees of freedom. Seven of 8 subjects preferred pattern recognition
      control over direct control. This study was the first home trial large enough to
      establish clinical and statistical significance in comparing pattern recognition
      with direct control. Results demonstrate that pattern recognition is a viable
      option and has functional advantages over direct control.

PMID- 29062021
TI  - Author Correction: The pattern-recognition receptor CORE of Solanaceae detects
      bacterial cold-shock protein.
AB  - In the version of this Article originally published, Fig. 6b, which is composed
      of individual pictures of six plants, inadvertently and erroneously displayed the
      same image of one Col-0 wt plant twice. This has been corrected so that Fig. 6b
      now shows two different representative plants for the Col-0 wt control.

PMID- 29062022
TI  - Temporal correlation detection using computational phase-change memory.
AB  - Conventional computers based on the von Neumann architecture perform computation
      by repeatedly transferring data between their physically separated processing and
      memory units. As computation becomes increasingly data centric and the
      scalability limits in terms of performance and power are being reached,
      alternative computing paradigms with collocated computation and storage are
      actively being sought. A fascinating such approach is that of computational
      memory where the physics of nanoscale memory devices are used to perform certain
      computational tasks within the memory unit in a non-von Neumann manner. We
      present an experimental demonstration using one million phase change memory
      devices organized to perform a high-level computational primitive by exploiting
      the crystallization dynamics. Its result is imprinted in the conductance states
      of the memory devices. The results of using such a computational memory for
      processing real-world data sets show that this co-existence of computation and
      storage at the nanometer scale could enable ultra-dense, low-power, and massively
      parallel computing systems.

PMID- 29062023
TI  - The effect of giant lateral collapses on magma pathways and the location of
      volcanism.
AB  - Flank instability and lateral collapse are recurrent processes during the
      structural evolution of volcanic edifices, and they affect and are affected by
      magmatic activity. It is known that dyke intrusions have the potential to
      destabilise the flanks of a volcano, and that lateral collapses may change the
      style of volcanism and the arrangement of shallow dykes. However, the effect of a
      large lateral collapse on the location of a new eruptive centre remains unclear.
      Here, we use a numerical approach to simulate the pathways of magmatic intrusions
      underneath the volcanic edifice, after the stress redistribution resulting from a
      large lateral collapse. Our simulations are quantitatively validated against the
      observations at Fogo volcano, Cabo Verde. The results reveal that a lateral
      collapse can trigger a significant deflection of deep magma pathways in the
      crust, favouring the formation of a new eruptive centre within the collapse
      embayment. Our results have implications for the long-term evolution of
      intraplate volcanic ocean islands.

PMID- 29062024
TI  - Conformational effects of N-glycan core fucosylation of immunoglobulin G Fc
      region on its interaction with Fcgamma receptor IIIa.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) is promoted through interaction
      between the Fc region of immunoglobulin G1 (IgG1) and Fcgamma receptor IIIa
      (FcgammaRIIIa), depending on N-glycosylation of these glycoproteins. In
      particular, core fucosylation of IgG1-Fc N-glycans negatively affects this
      interaction and thereby compromises ADCC activity. To address the mechanisms of
      this effect, we performed replica-exchange molecular dynamics simulations based
      on crystallographic analysis of a soluble form of FcgammaRIIIa (sFcgammaRIIIa) in
      complex with IgG1-Fc. Our simulation highlights increased conformational
      fluctuation of the N-glycan at Asn162 of sFcgammaRIIIa upon fucosylation of IgG1
      Fc, consistent with crystallographic data giving no interpretable electron
      density for this N-glycan, except for the innermost part. The fucose residue
      disrupts optimum intermolecular carbohydrate-carbohydrate interactions, rendering
      this sFcgammaRIIIa glycan distal from the Fc glycan. Moreover, our simulation
      demonstrates that core fucosylation of IgG1-Fc affects conformational dynamics
      and rearrangements of surrounding amino acid residues, typified by Tyr296 of IgG1
      Fc, which was more extensively involved in the interaction with sFcgammaRIIIa
      without Fc core fucosylation. Our findings offer a structural foundation for
      designing and developing therapeutic antibodies with improved ADCC activity.

PMID- 29062025
TI  - Nutrient Loading Fosters Seagrass Productivity Under Ocean Acidification.
AB  - The effects of climate change are likely to be dependent on local settings.
      Nonetheless, the compounded effects of global and regional stressors remain
      poorly understood. Here, we used CO2 vents to assess how the effects of ocean
      acidification on the seagrass, Posidonia oceanica, and the associated epiphytic
      community can be modified by enhanced nutrient loading. P. oceanica at ambient
      and low pH sites was exposed to three nutrient levels for 16 months. The response
      of P. oceanica to experimental conditions was assessed by combining analyses of
      gene expression, plant growth, photosynthetic pigments and epiphyte loading. At
      low pH, nutrient addition fostered plant growth and the synthesis of
      photosynthetic pigments. Overexpression of nitrogen transporter genes following
      nutrient additions at low pH suggests enhanced nutrient uptake by the plant. In
      addition, enhanced nutrient levels reduced the expression of selected antioxidant
      genes in plants exposed to low pH and increased epiphyte cover at both ambient
      and low pH. Our results show that the effects of ocean acidification on P.
      oceanica depend upon local nutrient concentration. More generally, our findings
      suggest that taking into account local environmental settings will be crucial to
      advance our understanding of the effects of global stressors on marine systems.

PMID- 29062026
TI  - Early-onset and classical forms of type 2 diabetes show impaired expression of
      genes involved in muscle branched-chain amino acids metabolism.
AB  - The molecular mechanisms responsible for the pathophysiological traits of type 2
      diabetes are incompletely understood. Here we have performed transcriptomic
      analysis in skeletal muscle, and plasma metabolomics from subjects with classical
      and early-onset forms of type 2 diabetes (T2D). Focused studies were also
      performed in tissues from ob/ob and db/db mice. We document that T2D, both early
      and late onset, are characterized by reduced muscle expression of genes involved
      in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks
      Analysis provided support to idea that the BCAA genes are relevant in the
      pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is
      impaired in skeletal muscle from T2D patients. In diabetic mice model we detected
      alterations in skeletal muscle proteins involved in BCAA metabolism but not in
      obese mice. Metabolomic analysis revealed increased levels of branched-chain keto
      acids (BCKA), and BCAA in plasma of T2D patients, which may result from the
      disruption of muscle BCAA management. Our data support the view that inhibition
      of genes involved in BCAA handling in skeletal muscle takes place as part of the
      pathophysiology of type 2 diabetes, and this occurs both in early-onset and in
      classical type 2 diabetes.

PMID- 29062028
TI  - 11beta-hydroxysteroid dehydrogenase type 1 has no effect on survival during
      experimental malaria but affects parasitemia in a parasite strain-specific
      manner.
AB  - Malaria is a global disease associated with considerable mortality and morbidity.
      An appropriately balanced immune response is crucial in determining the outcome
      of malarial infection. The glucocorticoid (GC) metabolising enzyme, 11beta
      hydroxysteroid dehydrogenase-1 (11beta-HSD1) converts intrinsically inert GCs
      into active GCs. 11beta-HSD1 shapes endogenous GC action and is immunomodulatory.
      We investigated the role of 11beta-HSD1 in two mouse models of malaria. 11beta
      HSD1 deficiency did not affect survival after malaria infection, but it increased
      disease severity and parasitemia in mice infected with Plasmodium chabaudi AS. In
      contrast, 11beta-HSD1 deficiency rather decreased parasitemia in mice infected
      with the reticulocyte-restricted parasite Plasmodium berghei NK65 1556Cl1.
      Malaria-induced antibody production and pathology were unaltered by 11beta-HSD1
      deficiency though plasma levels of IL-4, IL-6 and TNF-alpha were slightly
      affected by 11beta-HSD1 deficiency, dependent on the infecting parasite. These
      data suggest that 11beta-HSD1 is not crucial for survival of experimental
      malaria, but alters its progression in a parasite strain-specific manner.

PMID- 29062029
TI  - Genetic Characterization of Chinese fir from Six Provinces in Southern China and
      Construction of a Core Collection.
AB  - Large ex situ germplasm collections of plants generally contain significant
      diversity. A set of 700 well-conserved Chinese fir (Cunninghamia lanceolata
      (Lamb.) Hook) clones from six provinces in southern China in the ex situ gene
      bank of Longshan State Forest, was analyzed using 21 simple sequence repeat
      markers, with the aim of assessing the genetic diversity of these germplasm
      resources. Genetic analysis revealed extensive genetic variation among the
      accessions, with an average of 8.31 alleles per locus and a mean Shannon index of
      1.331. Excluding loci with null alleles, we obtained a low level of genetic
      differentiation among provinces, consistent with the interpopulation genetic
      variation (1%). Three clusters were identified by STRUCTURE, which did not match
      the individuals' geographical provenances. Ten traits related to growth and wood
      properties were quantified in these individuals, and there was substantial
      variation in all traits across individuals, these provide a potential source of
      variation for genetic improvement of the Chinese fir. Screening large collections
      for multiple-trait selective breeding programs is laborious and expensive; a core
      collection of 300 accessions, representative of the germplasm, was established,
      based on genotypic and phenotypic data. The identified small, but diverse,
      collections will be useful for further genome-wide association studies.

PMID- 29062027
TI  - Harnessing a catalytic lysine residue for the one-step preparation of homogeneous
      antibody-drug conjugates.
AB  - Current strategies to produce homogeneous antibody-drug conjugates (ADCs) rely on
      mutations or inefficient conjugation chemistries. Here we present a strategy to
      produce site-specific ADCs using a highly reactive natural buried lysine embedded
      in a dual variable domain (DVD) format. This approach is mutation free and drug
      conjugation proceeds rapidly at neutral pH in a single step without removing any
      charges. The conjugation chemistry is highly robust, enabling the use of crude
      DVD for ADC preparation. In addition, this strategy affords the ability to
      precisely monitor the efficiency of drug conjugation with a catalytic assay. ADCs
      targeting HER2 were prepared and demonstrated to be highly potent and specific in
      vitro and in vivo. Furthermore, the modular DVD platform was used to prepare
      potent and specific ADCs targeting CD138 and CD79B, two clinically established
      targets overexpressed in multiple myeloma and non-Hodgkin lymphoma, respectively.

PMID- 29062030
TI  - Cytolytic toxin production by Staphylococcus aureus is dependent upon the
      activity of the protoheme IX farnesyltransferase.
AB  - Staphylococcus aureus is a medically important pathogen with an abundance of
      virulence factors that are necessary for survival within a host, including the
      production of cytolytic toxins. The regulation of toxin production is mediated by
      the Agr quorum sensing system, and a poorly defined post-exponential growth phase
      signal independent of Agr. As part of a recent genome wide association study
      (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a
      polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase,
      was identified. This enzyme is essential for processing heme into the electron
      transport chain for use as an electron acceptor. Interestingly, without this
      enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and
      this appears to be mediated through repression of the Agr quorum sensing system.
      We hypothesize that the loss of electron transport is inducing feedback
      inhibition of metabolic capabilities that suppress the TCA cycle, and that this
      coupled with decreased RNAIII transcription prevents synthesis of cytolytic
      toxins.

PMID- 29062031
TI  - Effect of random feld disorder on topological superconductors.
AB  - We study the effect of random field disorder on two dimensional topological
      superconductors based on the Bogoliubov-de Gennes equations. A phase transition
      from the phase coherent state to the disordered state is identified numerically.
      The two phases can be characterized by two different correlation functions. In
      the phase coherent state, Majorana Fermion states form and may be influenced by
      the interaction between the vortex and the antivortex. The local density of
      states is calculated, which may be used to distinguish these two phases.

PMID- 29062032
TI  - Association between pulse wave velocity and hot flashes/sweats in middle-aged
      women.
AB  - As women age and go through menopause, they suffer a higher incidence of
      cardiovascular morbidity and mortality. Previous studies have shown that a
      relationship exists between hot flashes/sweats and an increased risk of
      cardiovascular disease. However, the association between hot flashes/sweats and
      arterial stiffness is unclear. We aim to explore the relationship between hot
      flashes/sweats and arterial stiffness using the modified Kupperman index (KMI)
      questionnaire and measure the brachial-ankle pulse wave velocity (baPWV). The
      prevalence of hot flashes in our research was reported to be 41.77%. There was a
      statistically significant difference between the mean baPWV among groups that
      experienced different severities of hot flashes/sweats according to one-way ANOVA
      test (p < 0.001). The baPWV values were positively associated with the severity
      of hot flashes/sweats based on linear regression after adjusting for established
      cardiovascular confounders (95% CI: (5.86, 43.23), p = 0.01). To the best of our
      knowledge, this study is the first investigation to propose that baPWV may serve
      both as an objective index for evaluating the severity of hot flashes/sweats and
      as a predictor of arterial stiffness beyond Cardiac Vascular Disease (CVD) risk
      factors in middle-aged women.

PMID- 29062033
TI  - Compared to self-immersion, mindful attention reduces salivation and automatic
      food bias.
AB  - Immersing ourselves in food images can sometimes make it feel subjectively real,
      as if the actual food were right in front of us. Excessive self-immersion into
      mental content, however, is a hallmark of psychological distress, and of several
      psychiatric conditions. Being aware that imagined events are not necessarily an
      accurate depiction of reality is a key feature of psychotherapeutic approaches
      akin to mindfulness-based interventions. Yet, it is still largely unknown to what
      extent one's engagement with mental content, considering it as real, biases one's
      automatic tendencies toward the world. In this study, we measured the change in
      subjective realism induced by a self-immersion and a mindful attention
      instruction, using self-reports and saliva volumes. Then, we measured
      behaviorally the impact of subjective realism changes on automatic approach bias
      toward attractive food (FAB) using an approach-avoidance task. We found a
      reduction in saliva volume, followed by a reduction in FAB in the mindful
      condition compared to the immersed condition. During the immersed condition only,
      saliva volumes, state and trait measures of subjective realism, and food craving
      traits were positively correlated with FAB values, whereas meditation experience
      was negatively correlated to it. We conclude that mindful attention instructions
      can de-automatize food bias.

PMID- 29062034
TI  - Comparative transcriptome analysis reveals host-associated differentiation in
      Chilo suppressalis (Lepidoptera: Crambidae).
AB  - The striped stem borer, Chilo suppressalis Walker (Lepidoptera: Crambidae), is
      one of the most serious rice pests. Besides attacking rice, it also feeds on an
      economically important vegetable crop, water-oat Zizania latifolia. The species
      feeding on water-oat has higher growth and survival rate than those on rice,
      suggesting their success in adaptation to the new host plant. However, little is
      known about the molecular mechanisms of host plant adaptation. Here we
      investigated the midgut transcriptome responses of C. suppressalis larvae reared
      on rice and water-oat. A total of 1,633 differentially expressed genes were
      identified, with a greater number up-regulated on the more delicious new host.
      The up-regulation of most digestive and detoxification-related genes may be the
      result of adaptation to the changes in nutritional requirements and toxic
      chemicals during host shift. In contrast, down-regulation of ribosomal genes may
      be related to their better development performance when feeding on the new host.
      In conclusion, our results suggest that transcriptional regulation of genes
      related to digestion, detoxification and ribosome may play an important role in
      adaptation of C. suppressalis to a new host plant.

PMID- 29062036
TI  - 3D Printing Bioinspired Ceramic Composites.
AB  - Natural structural materials like bone and shell have complex, hierarchical
      architectures designed to control crack propagation and fracture. In modern
      composites there is a critical trade-off between strength and toughness. Natural
      structures provide blueprints to overcome this, however this approach introduces
      another trade-off between fine structural manipulation and manufacturing complex
      shapes in practical sizes and times. Here we show that robocasting can be used to
      build ceramic-based composite parts with a range of geometries, possessing
      microstructures unattainable by other production technologies. This is achieved
      by manipulating the rheology of ceramic pastes and the shear forces they
      experience during printing. To demonstrate the versatility of the approach we
      have fabricated highly mineralized composites with microscopic Bouligand
      structures that guide crack propagation and twisting in three dimensions, which
      we have followed using an original in-situ crack opening technique. In this way
      we can retain strength while enhancing toughness by using strategies taken from
      crustacean shells.

PMID- 29062035
TI  - CSF tau is associated with impaired cortical plasticity, cognitive decline and
      astrocyte survival only in APOE4-positive Alzheimer's disease.
AB  - In Alzheimer's disease (AD) patients, apopoliprotein (APOE) polymorphism is the
      main genetic factor associated with more aggressive clinical course. However, the
      interaction between cerebrospinal fluid (CSF) tau protein levels and APOE
      genotype has been scarcely investigated. A possible key mechanism invokes the
      dysfunction of synaptic plasticity. We investigated how CSF tau interacts with
      APOE genotype in AD patients. We firstly explored whether CSF tau levels and APOE
      genotype influence disease progression and long-term potentiation (LTP)-like
      cortical plasticity as measured by transcranial magnetic stimulation (TMS) in AD
      patients. Then, we incubated normal human astrocytes (NHAs) with CSF collected
      from sub-groups of AD patients to determine whether APOE genotype and CSF
      biomarkers influence astrocytes survival. LTP-like cortical plasticity differed
      between AD patients with apolipoprotein E4 (APOE4) and apolipoprotein E3 (APOE3)
      genotype. Higher CSF tau levels were associated with more impaired LTP-like
      cortical plasticity and faster disease progression in AD patients with APOE4 but
      not APOE3 genotype. Apoptotic activity was higher when cells were incubated with
      CSF from AD patients with APOE4 and high tau levels. CSF tau is detrimental on
      cortical plasticity, disease progression and astrocyte survival only when
      associated with APOE4 genotype. This is relevant for new therapeutic approaches
      targeting tau.

PMID- 29062037
TI  - Abrupt stop of deep water turnover with lake warming: Drastic consequences for
      algal primary producers.
AB  - After strong fertilization in the 20th century, many deep lakes in Central Europe
      are again nutrient poor due to long-lasting restoration (re-oligotrophication).
      In line with reduced phosphorus and nitrogen loadings, total organismic
      productivity decreased and lakes have now historically low nutrient and biomass
      concentrations. This caused speculations that restoration was overdone and
      intended fertilizations are needed to ensure ecological functionality. Here we
      show that recent re-oligotrophication processes indeed accelerated, however
      caused by lake warming. Rising air temperatures strengthen thermal stabilization
      of water columns which prevents thorough turnover (holomixis). Reduced mixis
      impedes down-welling of oxygen rich epilimnetic (surface) and up-welling of
      phosphorus and nitrogen rich hypolimnetic (deep) water. However, nutrient inputs
      are essential for algal spring blooms acting as boost for annual food web
      successions. We show that repeated lack (since 1977) and complete stop (since
      2013) of holomixis caused drastic epilimnetic phosphorus depletions and an
      absence of phytoplankton spring blooms in Lake Zurich (Switzerland). By
      simulating holomixis in experiments, we could induce significant vernal algal
      blooms, confirming that there would be sufficient hypolimnetic phosphorus which
      presently accumulates due to reduced export. Thus, intended fertilizations are
      highly questionable, as hypolimnetic nutrients will become available during
      future natural or artificial turnovers.

PMID- 29062038
TI  - The Src family kinase LCK cooperates with oncogenic FLT3/ITD in cellular
      transformation.
AB  - The non-receptor tyrosine kinase LCK belongs to the SRC family of kinases. SRC
      family kinases are proto-oncogenes that have long been known to play key roles in
      cell proliferation, motility, morphology and survival. Here we show that LCK
      regulates the function of the type III receptor tyrosine kinase FLT3 in murine
      pro-B cells. We observed that expression of LCK significantly enhances the colony
      forming capacity of the constitutively active FLT3 mutant FLT3-ITD (internal
      tandem duplication). Furthermore, cells expressing LCK developed tumor earlier
      compared to cells transfected with empty control vector. Staining of the tissues
      from mouse xenografts showed higher Ki67 staining in cells expressing LCK
      suggesting that expression of LCK enhances the FLT3-ITD-mediated proliferative
      capacity. LCK expression did not affect either FLT3-WT or FLT3-ITD -induced AKT,
      ERK1/2 or p38 phosphorylation. However, LCK expression significantly enhanced
      FLT3-ITD-mediated STAT5 phosphorylation. Taken together, our data suggest that
      LCK cooperates with oncogenic FLT3-ITD in cellular transformation.

PMID- 29062040
TI  - Regiospecific Synthesis of Ring A Fused Withaferin A Isoxazoline Analogues:
      Induction of Premature Senescence by W-2b in Proliferating Cancer Cells.
AB  - Induction of premature senescence represents a novel functional strategy to curb
      the uncontrolled proliferation of malignant cancer cells. This study unveils the
      regiospecific synthesis of novel isoxazoline derivatives condensed to ring A of
      medicinal plant product Withaferin-A. Intriguingly, the cis fused products with
      beta-oriented hydrogen exhibited excellent cytotoxic activities against
      proliferating human breast cancer MCF7 and colorectal cancer HCT-116 cells. The
      most potent derivative W-2b triggered premature senescence along with increase in
      senescence-associated beta-galactosidase activity, G2/M cell cycle arrest, and
      induction of senescence-specific marker p21Waf1/Cip1 at its sub-toxic
      concentration. W-2b conferred a robust increase in phosphorylation of mammalian
      checkpoint kinase-2 (Chk2) in cancer cells in a dose-dependent manner. Silencing
      of endogenous Chk2 by siRNA divulged that the amplification of p21 expression and
      senescence by W-2b was Chk2-dependent. Chk2 activation (either by ectopic
      overexpression or through treatment with W-2b) suppressed NM23-H1 signaling axis
      involved in cancer cell proliferation. Finally, W-2b showed excellent in vivo
      efficacy with 83.8% inhibition of tumor growth at a dose of 25 mg/kg, b.w. in
      mouse mammary carcinoma model. Our study claims that W-2b could be a potential
      candidate to limit aberrant cellular proliferation rendering promising
      improvement in the treatment regime in cancer patients.

PMID- 29062039
TI  - A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit.
AB  - Mutations in IDH1 are highly prevalent in human glioma. First line treatment is
      radiotherapy, which many patients often forego to avoid treatment-associated
      morbidities. The high prevalence of IDH1 mutations in glioma highlights the need
      for brain-penetrant IDH1 mutant-selective inhibitors as an alternative
      therapeutic option. Here, we have explored the utility of such an inhibitor in
      IDH1 mutant patient-derived models to assess the potential therapeutic benefits
      associated with intracranial 2-HG inhibition. Treatment of mutant IDH1 cell line
      models led to a decrease in intracellular 2-HG levels both in vitro and in vivo.
      Interestingly, inhibition of 2-HG production had no effect on in vitro IDH1
      mutant glioma cell proliferation. In contrast, IDH1 mutant-selective inhibitors
      provided considerable survival benefit in vivo. However, even with near complete
      inhibition of intratumoral 2-HG production, not all mutant glioma models
      responded to treatment. The results suggest that disruption of 2-HG production
      with brain-penetrant inhibitors in IDH1 mutant gliomas may have substantial
      patient benefit.

PMID- 29062041
TI  - Canonical NFkappaB signaling in myeloid cells is required for the glioblastoma
      growth.
AB  - Tumor development and therapeutic resistance are linked with tumor-associated
      macrophage (TAM) and myeloid-derived suppressor cell (MDSC) infiltration in
      tumors via chemokine axis. Chemokine expression, which determines the pro or anti
      inflammatory status of myeloid cells, are partly regulated by the nuclear factor
      kappa B (NF-kappaB) pathway. Here, we identified that conditional deletion of
      canonical NF-kappaB signaling (p65) in myeloid cells inhibited syngeneic
      glioblastoma (GBM) through decreased CD45 infiltration in tumors, as
      characterized by decreased TAMs (CD206+) and MDSCs (Gr1+ CD11b+), increased
      dendritic cells (CD86+) and cytotoxic T cells (CD8+) in the p65 knockout (KO)
      mice. Proinflammatory cytokines (IFNgamma, MCP1, MIP1alpha, and TNFalpha) and
      myeloid differentiation factor (Endoglin) were increased in myeloid cells from
      p65 KO tumor, which demonstrated an influence on CD8+T cell proliferation. In
      contrast, p65KO athymic chimeric mice with human GBM, failed to inhibit tumor
      growth, confirming the contribution of T cells in an immune competent model. The
      analysis of human datasets and GBM tumors revealed higher expression of p65 in
      GBM-associated CD68+ macrophages compared to neighboring stroma. Thus, canonical
      NF-kappaB signaling has an anti-inflammatory role and is required for macrophage
      polarization, immune suppression, and GBM growth. Combining an NF-kappaB
      inhibitor with standard therapy could improve antitumor immunity in GBM.

PMID- 29062042
TI  - Contributions of MyD88-dependent receptors and CD11c-positive cells to corneal
      epithelial barrier function against Pseudomonas aeruginosa.
AB  - Previously we reported that corneal epithelial barrier function against
      Pseudomonas aeruginosa was MyD88-dependent. Here, we explored contributions of
      MyD88-dependent receptors using vital mouse eyes and confocal imaging. Uninjured
      IL-1R (-/-) or TLR4 (-/-) corneas, but not TLR2 (-/-), TLR5 (-/-), TLR7 (-/-), or
      TLR9 (-/-), were more susceptible to P. aeruginosa adhesion than wild-type (3.8
      fold, 3.6-fold respectively). Bacteria adherent to the corneas of IL-1R (-/-) or
      TLR5 (-/-) mice penetrated beyond the epithelial surface only if the cornea was
      superficially-injured. Bone marrow chimeras showed that bone marrow-derived cells
      contributed to IL-1R-dependent barrier function. In vivo, but not ex vivo,
      stromal CD11c+ cells responded to bacterial challenge even when corneas were
      uninjured. These cells extended processes toward the epithelial surface, and co
      localized with adherent bacteria in superficially-injured corneas. While CD11c+
      cell depletion reduced IL-6, IL-1beta, CXCL1, CXCL2 and CXCL10 transcriptional
      responses to bacteria, and increased susceptibility to bacterial adhesion (>3
      fold), the epithelium remained resistant to bacterial penetration. IL-1R (-/-)
      corneas also showed down-regulation of IL-6 and CXCL1 genes with and without
      bacterial challenge. These data show complex roles for TLR4, TLR5, IL-1R and
      CD11c+ cells in constitutive epithelial barrier function against P. aeruginosa,
      with details dependent upon in vivo conditions.

PMID- 29062043
TI  - Synthesis of Reduced Grapheme Oxide as A Platform for loading beta
      NaYF4:Ho3+@TiO2Based on An Advanced Visible Light-Driven Photocatalyst.
AB  - In this paper a novel visible light-driven ternary compound photocatalyst (beta
      NaYF4:Ho3+@TiO2-rGO) was synthesized using a three-step approach. This
      photocatalyst was characterized using X-ray diffraction, Raman scattering
      spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy,
      Transmission electron microscopy, X-ray photoelectron spectroscopy, fluorescence
      spectrometries, ultraviolet-visible diffuse reflectance spectroscopy, Brunauer
      Emmett-Teller surface area measurement, electron spin resonance, three
      dimensional fluorescence spectroscopy, and photoelectrochemical properties. Such
      proposed photocatalyst can absorb 450 nm visible light while emit 290 nm
      ultraviolet light, so as to realize the visible light-driven photocatalysis of
      TiO2. In addition, as this tenary compound photocatalyst enjoys effecitve
      capacity of charge separation, superior durability, and sound adsorb ability of
      RhB, it can lead to the red shift of wavelength of absorbed light. This novel
      tenary photocatalyst can reach decomposition rate of RhB as high as 92% after 10
      h of irradiation by visible-light Xe lamp. Compared with the blank experiment,
      the efficiency was significantly improved. Recycle experiments showed that
      thebeta-NaYF4:Ho3+@TiO2-rGOcomposites still presented significant photocatalytic
      activity after four successive cycles. Finally, we investigated visible-light
      responsive photocatalytic mechanism of the beta-NaYF4:Ho3+@TiO2-rGO composites.
      It is of great significance to design an effective solar light-driven
      photocatalysis in promoting environmental protection.

PMID- 29062044
TI  - A short linear motif in scaffold Nup145C connects Y-complex with pre-assembled
      outer ring Nup82 complex.
AB  - Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs), which
      are formed from multiple copies of ~30 different nucleoporins (Nups) and inserted
      into the double nuclear membrane. Many of these Nups are organized into
      subcomplexes, of which the Y-shaped Nup84 complex is the major constituent of the
      nuclear and cytoplasmic rings. The Nup82-Nup159-Nsp1 complex is another module
      that, however, is only assembled into the cytoplasmic ring. By means of
      crosslinking mass spectrometry, biochemical reconstitution, and molecular
      modeling, we identified a short linear motif in the unstructured N-terminal
      region of Chaetomium thermophilum Nup145C, a subunit of the Y-complex, that is
      sufficient to recruit the Nup82 complex, but only in its assembled state. This
      finding points to a more general mechanism that short linear motifs in structural
      Nups can act as sensors to cooperatively connect pre-assembled NPC modules,
      thereby facilitating the formation and regulation of the higher-order NPC
      assembly.

PMID- 29062046
TI  - Outlining tectonic inheritance and construction of the Min Shan region, eastern
      Tibet, using crustal geometry.
AB  - The ongoing collision between India and Eurasia has created the Tibetan Plateau,
      which features high elevations and large crustal thicknesses. The easternmost
      portion of the plateau has long been a key region for studying the uplift
      mechanism of the Tibetan Plateau, especially after the 2008 Ms. 7.9 Wenchuan
      earthquake. However, previous studies have assumed that easternmost Tibet is
      tectonically homogeneous, and the tectonic significance of the Min Shan has been
      overshadowed by that of its more conspicuous neighbour, the Longmen Shan region.
      Here, we describe the crustal geometry of the Min Shan region using two newly
      obtained deep seismic reflection profiles. In this study, we identify an upper
      lower crust mechanical decoupling within the Min Shan region; the Min Shan region
      is tectonically delineated by an inherited boundary fault zone, the Huya fault
      zone, which was responsible for triggering the 2017 Jiuzhaigou M 7.0 earthquake.
      Together with the gravity dataset and previous studies in this area, the outlined
      crustal geometry indicated that crustal-scale shortening at the eastern plateau
      margin is a primary mechanism driving uplift, although extensive uplift might
      have occurred due to the decoupled shortening between the upper and lower crust.

PMID- 29062045
TI  - Evolution of AF6-RAS association and its implications in mixed-lineage leukemia.
AB  - Elucidation of activation mechanisms governing protein fusions is essential for
      therapeutic development. MLL undergoes rearrangement with numerous partners,
      including a recurrent translocation fusing the epigenetic regulator to a
      cytoplasmic RAS effector, AF6/afadin. We show here that AF6 employs a non
      canonical, evolutionarily conserved alpha-helix to bind RAS, unique to AF6 and
      the classical RASSF effectors. Further, all patients with MLL-AF6 translocations
      express fusion proteins missing only this helix from AF6, resulting in exposure
      of hydrophobic residues that induce dimerization. We provide evidence that
      oligomerization is the dominant mechanism driving oncogenesis from rare MLL
      translocation partners and employ our mechanistic understanding of MLL-AF6 to
      examine how dimers induce leukemia. Proteomic data resolve association of
      dimerized MLL with gene expression modulators, and inhibiting dimerization
      disrupts formation of these complexes while completely abrogating leukemogenesis
      in mice. Oncogenic gene translocations are thus selected under pressure from
      protein structure/function, underscoring the complex nature of chromosomal
      rearrangements.

PMID- 29062048
TI  - Nacre-mimic Reinforced Ag@reduced Graphene Oxide-Sodium Alginate Composite Film
      for Wound Healing.
AB  - With the emerging of drug-resistant bacterial and fungal pathogens, there raise
      the interest of utilizing versatile antimicrobial biomaterials to treat the acute
      wound. Herein, we report the spraying mediated assembly of a bio-inspired
      Ag@reduced graphene-sodium alginate (AGSA) composite film for effective wound
      healing. The obtained film displayed lamellar microstructures similar to the
      typical "brick-and-mortar" structure in nacre. In this nacre-mimic structure,
      there are abundant interfacial interactions between nanosheets and polymeric
      matrix, leading to remarkable reinforcement. As a result, the tensile strength,
      toughness and Young's modulus have been improved 2.8, 2.3 and 2.7 times compared
      with pure sodium alginate film, respectively. In the wound healing study, the
      AGSA film showed effective antimicrobial activities towards Pseudomonas
      aeruginosa, Escherichia coli and Candida albicans, demonstrating the ability of
      protecting wound from pathogenic microbial infections. Furthermore, in vivo
      experiments on rats suggested the effect of AGSA film in promoting the recovery
      of wound sites. According to MTT assays, heamolysis evaluation and in vivo
      toxicity assessment, the composite film could be applied as a bio-compatible
      material in vitro and in vivo. Results from this work indicated such AGSA film
      has promising performance for wound healing and suggested great potential for
      nacre-mimic biomaterials in tissue engineering applications.

PMID- 29062047
TI  - Protein-peptide association kinetics beyond the seconds timescale from atomistic
      simulations.
AB  - Understanding and control of structures and rates involved in protein ligand
      binding are essential for drug design. Unfortunately, atomistic molecular
      dynamics (MD) simulations cannot directly sample the excessively long residence
      and rearrangement times of tightly binding complexes. Here we exploit the
      recently developed multi-ensemble Markov model framework to compute full protein
      peptide kinetics of the oncoprotein fragment 25-109Mdm2 and the nano-molar
      inhibitor peptide PMI. Using this system, we report, for the first time, direct
      estimates of kinetics beyond the seconds timescale using simulations of an all
      atom MD model, with high accuracy and precision. These results only require
      explicit simulations on the sub-milliseconds timescale and are tested against
      existing mutagenesis data and our own experimental measurements of the
      dissociation and association rates. The full kinetic model reveals an overall
      downhill but rugged binding funnel with multiple pathways. The overall strong
      binding arises from a variety of conformations with different hydrophobic contact
      surfaces that interconvert on the milliseconds timescale.

PMID- 29062049
TI  - The role of grain boundary scattering in reducing the thermal conductivity of
      polycrystalline XNiSn (X = Hf, Zr, Ti) half-Heusler alloys.
AB  - Thermoelectric application of half-Heusler compounds suffers from their fairly
      high thermal conductivities. Insight into how effective various scattering
      mechanisms are in reducing the thermal conductivity of fabricated XNiSn compounds
      (X = Hf, Zr, Ti, and mixtures thereof) is therefore crucial. Here, we show that
      such insight can be obtained through a concerted theory-experiment comparison of
      how the lattice thermal conductivity kappa Lat(T) depends on temperature and
      crystallite size. Comparing theory and experiment for a range of Hf0.5Zr0.5NiSn
      and ZrNiSn samples reported in the literature and in the present paper revealed
      that grain boundary scattering plays the most important role in bringing down
      kappa Lat, in particular so for unmixed compounds. Our concerted analysis
      approach was corroborated by a good qualitative agreement between the measured
      and calculated kappa Lat of polycrystalline samples, where the experimental
      average crystallite size was used as an input parameter for the calculations. The
      calculations were based on the Boltzmann transport equation and ab initio density
      functional theory. Our analysis explains the significant variation of reported
      kappa Lat of nominally identical XNiSn samples, and is expected to provide
      valuable insights into the dominant scattering mechanisms even for other
      materials.

PMID- 29062050
TI  - Functional expression and pharmaceutical efficacy of cardiac-specific ion
      channels in human embryonic stem cell-derived cardiomyocytes.
AB  - Cardiomyocytes differentiated from human pluripotent stem cells provide promising
      tools for screening of cardiotoxic drugs. For evaluation of human pluripotent
      stem cell-derived cardiomyocytes for cardiotoxicity test, in the present study,
      human embryonic stem cells (hESCs) were differentiated to cardiomyocytes,
      followed by metabolic selection to enrich the differentiated cardiomyocytes. The
      highly purified hESC-derived cardiomyocytes (hESC-CMs) expressed several
      cardiomyocyte-specific markers including cTnT, MLC2a, and alpha-SA, but not
      pluripotency markers, such as OCT4 and NANOG. Patch clamp technique and RT-PCR
      revealed the expression of cardiomyocyte-specific Na+, Ca2+, and K+ channels and
      cardiac action potential in hESC-CMs. To explore the potential use of hESC-CMs as
      functional cardiomyocytes for drug discovery and cardiotoxicity screening, we
      examined the effects of bisindolylmaleimide (BIM) (I), which inhibits native
      cardiac Ca2+ channels, on the Ca2+ channel activity of hESC-CMs. We observed a
      similar response for the BIM (I)-induced modulation of Ca2+ channels between hESC
      CMs and native cardiomyocytes through L-type Ca2+ channel current. These results
      suggest that hESC-CMs can be useful for evaluation of pharmaceutical efficacy and
      safety of novel drug candidate in cardiac research.

PMID- 29062051
TI  - Gene expression atlas of fruit ripening and transcriptome assembly from RNA-seq
      data in octoploid strawberry (Fragaria * ananassa).
AB  - RNA-seq has been used to perform global expression analysis of the achene and the
      receptacle at four stages of fruit ripening, and of the roots and leaves of
      strawberry (Fragaria * ananassa). About 967 million reads and 191 Gb of sequence
      were produced, using Illumina sequencing. Mapping the reads in the related genome
      of the wild diploid Fragaria vesca revealed differences between the achene and
      receptacle development program, and reinforced the role played by ethylene in the
      ripening receptacle. For the strawberry transcriptome assembly, a de novo
      strategy was followed, generating separate assemblies for each of the ten tissues
      and stages sampled. The Trinity program was used for these assemblies, resulting
      in over 1.4 M isoforms. Filtering by a threshold of 0.3 FPKM, and doing Blastx (E
      value < 1 e-30) against the UniProt database of plants reduced the number to
      472,476 isoforms. Their assembly with the MIRA program (90% homology) resulted in
      26,087 contigs. From these, 91.34 percent showed high homology to Fragaria vesca
      genes and 87.30 percent Fragaria iinumae (BlastN E-value < 1 e-100). Mapping back
      the reads on the MIRA contigs identified polymorphisms at nucleotide level, using
      FREEBAYES, as well as estimate their relative abundance in each sample.

PMID- 29062052
TI  - Evolutionary history biases inferences of ecology and environment from delta13C
      but not delta18O values.
AB  - Closely related taxa are, on average, more similar in terms of their physiology,
      morphology and ecology than distantly related ones. How this biological
      similarity affects geochemical signals, and their interpretations, has yet to be
      tested in an explicitly evolutionary framework. Here we compile and analyze
      planktonic foraminiferal size-specific stable carbon and oxygen isotope values
      (delta13C and delta18O, respectively) spanning the last 107 million years. After
      controlling for dominant drivers of size-delta13C and size-delta18O trends, such
      as geological preservation, presence of algal photosymbionts, and global
      environmental changes, we identify that shared evolutionary history has shaped
      the evolution of species-specific vital effects in delta13C, but not in delta18O.
      Our results lay the groundwork for using a phylogenetic approach to correct
      species delta13C vital effects through time, thereby reducing systematic biases
      in interpretations of long-term delta13C records-a key measure of holistic
      organismal biology and of the global carbon cycle.

PMID- 29062055
TI  - Genetic engineering: On the road to efficient gene drives.

PMID- 29062053
TI  - Spontaneous circadian rhythms in a cold-adapted natural isolate of Aureobasidium
      pullulans.
AB  - Circadian systems enable organisms to synchronize their physiology to daily and
      seasonal environmental changes relying on endogenous pacemakers that oscillate
      with a period close to 24 h even in the absence of external timing cues. The
      oscillations are achieved by intracellular transcriptional/translational feedback
      loops thoroughly characterized for many organisms, but still little is known
      about the presence and characteristics of circadian clocks in fungi other than
      Neurospora crassa. We sought to characterize the circadian system of a natural
      isolate of Aureobasidium pullulans, a cold-adapted yeast bearing great
      biotechnological potential. A. pullulans formed daily concentric rings that were
      synchronized by light/dark cycles and were also formed in constant darkness with
      a period of 24.5 h. Moreover, these rhythms were temperature compensated, as
      evidenced by experiments conducted at temperatures as low as 10  degrees C.
      Finally, the expression of clock-essential genes, frequency, white collar-1,
      white collar-2 and vivid was confirmed. In summary, our results indicate the
      existence of a functional circadian clock in A. pullulans, capable of sustaining
      rhythms at very low temperatures and, based on the presence of conserved clock
      gene homologues, suggest a molecular and functional relationship to well
      described circadian systems.

PMID- 29062056
TI  - Transcription: Intragenic enhancers dampen gene expression.

PMID- 29062054
TI  - Integrated analysis of mRNA and viral miRNAs in the kidney of Carassius auratus
      gibelio response to cyprinid herpesvirus 2.
AB  - MicroRNAs (miRNAs) are small, non-coding single stranded RNAs that play crucial
      roles in numerous biological processes. Vertebrate herpesviruses encode multiple
      viral miRNAs that modulate host and viral genes. However, the roles of viral
      miRNAs in lower vertebrates have not been fully determined. Here, we used high
      throughput sequencing to analyse the miRNA and mRNA expression profiles of
      Carassius auratus gibelio in response to infection by cyprinid herpesvirus 2
      (CyHV-2). RNA sequencing obtained 26,664 assembled transcripts, including 2,912
      differentially expressed genes. Based on small RNA sequencing and secondary
      structure predictions, we identified 17 CyHV-2 encoded miRNAs, among which 14
      were validated by stem-loop quantitative real-time reverse transcription
      polymerase chain reaction (qRT-PCR) and eight were validated by northern
      blotting. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathway analysis of miRNAs-mRNA pairs revealed diverse affected
      immune signalling pathways, including the RIG-I-like receptor and JAK-STAT
      pathways. Finally, we presented four genes involved in RIG-I-like pathways,
      including host gene IRF3, RBMX, PIN1, viral gene ORF4, which are negatively
      regulated by CyHV-2 encoded miRNA miR-C4. The present study is the first to
      provide a comprehensive overview of viral miRNA-mRNA co-regulation, which might
      have a key role in controlling post-transcriptomic regulation during CyHV-2
      infection.

PMID- 29062058
TI  - All-angle Negative Reflection with An Ultrathin Acoustic Gradient Metasurface:
      Floquet-Bloch Modes Perspective and Experimental Verification.
AB  - Metasurface with gradient phase response offers new alternative for steering the
      propagation of waves. Conventional Snell's law has been revised by taking the
      contribution of local phase gradient into account. However, the requirement of
      momentum matching along the metasurface sets its nontrivial beam manipulation
      functionality within a limited-angle incidence. In this work, we theoretically
      and experimentally demonstrate that the acoustic gradient metasurface supports
      the negative reflection for all-angle incidence. The mode expansion theory is
      developed to help understand how the gradient metasurface tailors the incident
      beams, and the all-angle negative reflection occurs when the first negative order
      Floquet-Bloch mode dominates inside the metasurface slab. The coiling-up space
      structures are utilized to build desired acoustic gradient metasurface, and the
      all-angle negative reflections have been perfectly verified by experimental
      measurements. Our work offers the Floquet-Bloch modes perspective for
      qualitatively understanding the reflection behaviors of the acoustic gradient
      metasurface, and the all-angle negative reflection characteristic possessed by
      acoustic gradient metasurface could enable a new degree of the acoustic wave
      manipulating and be applied in the functional diffractive acoustic elements, such
      as the all-angle acoustic back reflector.

PMID- 29062057
TI  - Population genetics of sexual conflict in the genomic era.
AB  - Sexual conflict occurs when selection acts in opposing directions on males and
      females. Case studies in both vertebrates and invertebrates indicate that sexual
      conflict maintains genetic diversity through balancing selection, which might
      explain why many populations show more genetic variation than expected. Recent
      population genomic approaches based on different measures of balancing selection
      have suggested that sexual conflict can arise over survival, not just
      reproductive fitness as previously thought. A fuller understanding of sexual
      conflict will provide insight into its contribution to adaptive evolution and
      will reveal the constraints it might impose on populations.

PMID- 29062059
TI  - Elucidation of Plasma-induced Chemical Modifications on Glutathione and
      Glutathione Disulphide.
AB  - Cold atmospheric pressure plasmas are gaining increased interest in the medical
      sector and clinical trials to treat skin diseases are underway. Plasmas are
      capable of producing several reactive oxygen and nitrogen species (RONS).
      However, there are open questions how plasma-generated RONS interact on a
      molecular level in a biological environment, e.g. cells or cell components. The
      redox pair glutathione (GSH) and glutathione disulphide (GSSG) forms the most
      important redox buffer in organisms responsible for detoxification of
      intracellular reactive species. We apply Raman spectroscopy, mass spectrometry,
      and molecular dynamics simulations to identify the time-dependent chemical
      modifications on GSH and GSSG that are caused by dielectric barrier discharge
      under ambient conditions. We find GSSG, S-oxidised glutathione species, and S
      nitrosoglutathione as oxidation products with the latter two being the final
      products, while glutathione sulphenic acid, glutathione sulphinic acid, and GSSG
      are rather reaction intermediates. Experiments using stabilized pH conditions
      revealed the same main oxidation products as were found in unbuffered solution,
      indicating that the dominant oxidative or nitrosative reactions are not
      influenced by acidic pH. For more complex systems these results indicate that too
      long treatment times can cause difficult-to-handle modifications to the cellular
      redox buffer which can impair proper cellular function.

PMID- 29062061
TI  - A Maternal Two-meal Feeding Sequence with Varying Crude Protein Affects Milk
      Lipid Profile in A Sow-Piglet Model.
AB  - The effects of a two-meal feeding sequence on production performance and milk
      lipid profile were investigated. Sixty pregnant sows (d 85 of gestation) were
      assigned to 3 groups: 2 C group (fed a control crude protein [CP] diet at 0600
      and 1500 daily), LH group (fed a low CP diet and a high CP diet at 0600 and
      1500), or HL group (fed a high CP diet and a low CP diet at 0600 and 1500).
      Reproductive performance of sows, and lipid profiles of plasma and milk were
      measured. Results showed that the HL feeding sequence dramatically increased
      average piglet weight/litter, average daily gain of piglet/litter, and milk
      production of sows. LH feeding sequence increased milk fat proportion, and HL
      feeding sequence significantly increased the proportion of milk MUFA on d 14 and
      21 of lactation. Interestingly, the HL feeding sequence also reduced the ratio of
      C18:1 cis /C18:1 trans in milk, which may account for the greater milk production
      of sows and growth performance of piglets during lactation. These findings
      indicated that both the maternal two-meal feeding sequences with varying crude
      protein improved milk production and milk lipid profiles of sows, which might
      contribute to improving growth performance of piglets.

PMID- 29062060
TI  - Role of HIV exposure and infection in relation to neonatal GBS disease and
      rectovaginal GBS carriage: a systematic review and meta-analysis.
AB  - Streptococcus agalactiae (GBS) is the leading cause worldwide of neonatal sepsis.
      We sought to assess to which extent HIV exposure of neonates is associated with
      GBS neonatal disease. Furthermore, we assessed to which extent HIV infection in
      women is associated with maternal rectovaginal GBS carriage, the single most
      important risk factor for GBS neonatal disease. We searched Pubmed, Embase, and
      Web of Science for studies assessing the association between neonatal GBS disease
      and HIV-status of the mother and studies that assessed the association between
      rectovaginal GBS colonization and HIV status in women. HIV-exposed uninfected
      neonates were more than twice as likely to have neonatal GBS disease compared to
      unexposed neonates. HIV-exposed neonates were not at increased risk for early
      onset neonatal disease, but were 4.43 times more likely to have late-onset
      neonatal GBS disease. There was no significant association between HIV infection
      status and rectovaginal GBS carriage. Public health interventions preventing
      neonatal GBS disease are urgently needed for the increasing group of HIV-exposed
      neonates. A framework integrating and explaining our findings highlights
      opportunities for the clinical practice and global health policy to prevent
      disease. Well-designed studies should clarify the relation between HIV-status and
      GBS carriage.

PMID- 29062062
TI  - Localised genetic heterogeneity provides a novel mode of evolution in dsDNA
      phages.
AB  - The Red Queen hypothesis posits that antagonistic co-evolution between
      interacting species results in recurrent natural selection via constant cycles of
      adaptation and counter-adaptation. Interactions such as these are at their most
      profound in host-parasite systems, with bacteria and their viruses providing the
      most intense of battlefields. Studies of bacteriophage evolution thus provide
      unparalleled insight into the remarkable elasticity of living entities. Here, we
      report a novel phenomenon underpinning the evolutionary trajectory of a group of
      dsDNA bacteriophages known as the phiKMVviruses. Employing deep next generation
      sequencing (NGS) analysis of nucleotide polymorphisms we discovered that this
      group of viruses generates enhanced intraspecies heterogeneity in their genomes.
      Our results show the localisation of variants to genes implicated in adsorption
      processes, as well as variation of the frequency and distribution of SNPs within
      and between members of the phiKMVviruses. We link error-prone DNA polymerase
      activity to the generation of variants. Critically, we show trans-activity of
      this phenomenon (the ability of a phiKMVvirus to dramatically increase genetic
      variability of a co-infecting phage), highlighting the potential of phages
      exhibiting such capabilities to influence the evolutionary path of other viruses
      on a global scale.

PMID- 29062063
TI  - Identification of candidate drugs using tensor-decomposition-based unsupervised
      feature extraction in integrated analysis of gene expression between diseases and
      DrugMatrix datasets.
AB  - Identifying drug target genes in gene expression profiles is not straightforward.
      Because a drug targets proteins and not mRNAs, the mRNA expression of drug target
      genes is not always altered. In addition, the interaction between a drug and
      protein can be context dependent; this means that simple drug incubation
      experiments on cell lines do not always reflect the real situation during active
      disease. In this paper, I applied tensor-decomposition-based unsupervised feature
      extraction to the integrated analysis using a mathematical product of gene
      expression in various diseases and gene expression in the DrugMatrix dataset,
      where comprehensive data on gene expression during various drug treatments of
      rats are reported. I found that this strategy, in a fully unsupervised manner,
      enables researchers to identify a combined set of genes and compounds that
      significantly overlap with gene and drug interactions identified in the past. As
      an example illustrating the usefulness of this strategy in drug discovery
      experiments, I considered cirrhosis, for which no effective drugs have ever been
      proposed. The present strategy identified two promising therapeutic-target genes,
      CYPOR and HNFA4; for their protein products, bezafibrate was identified as a
      promising candidate drug, supported by in silico docking analysis.

PMID- 29062064
TI  - Desulfation of Heparan Sulfate by Sulf1 and Sulf2 Is Required for Corticospinal
      Tract Formation.
AB  - Heparan sulfate (HS) has been implicated in a wide range of cell signaling. Here
      we report a novel mechanism in which extracellular removal of 6-O-sulfate groups
      from HS by the endosulfatases, Sulf1 and Sulf2, is essential for axon guidance
      during development. In Sulf1/2 double knockout (DKO) mice, the corticospinal
      tract (CST) was dorsally displaced on the midbrain surface. In utero
      electroporation of Sulf1/2 into radial glial cells along the third ventricle,
      where Sulf1/2 mRNAs are normally expressed, rescued the CST defects in the DKO
      mice. Proteomic analysis and functional testing identified Slit2 as the key
      molecule associated with the DKO phenotype. In the DKO brain, 6-O-sulfated HS was
      increased, leading to abnormal accumulation of Slit2 protein on the pial surface
      of the cerebral peduncle and hypothalamus, which caused dorsal repulsion of CST
      axons. Our findings indicate that postbiosynthetic desulfation of HS by Sulfs
      controls CST axon guidance through fine-tuning of Slit2 presentation.

PMID- 29062066
TI  - Electric polarization switching in an atomically thin binary rock salt structure.
AB  - Inducing and controlling electric dipoles is hindered in the ultrathin limit by
      the finite screening length of surface charges at metal-insulator junctions 1-3 ,
      although this effect can be circumvented by specially designed interfaces 4 .
      Heterostructures of insulating materials hold great promise, as confirmed by
      perovskite oxide superlattices with compositional substitution to artificially
      break the structural inversion symmetry 5-8 . Bringing this concept to the
      ultrathin limit would substantially broaden the range of materials and
      functionalities that could be exploited in novel nanoscale device designs. Here,
      we report that non-zero electric polarization can be induced and reversed in a
      hysteretic manner in bilayers made of ultrathin insulators whose electric
      polarization cannot be switched individually. In particular, we explore the
      interface between ionic rock salt alkali halides such as NaCl or KBr and polar
      insulating Cu2N terminating bulk copper. The strong compositional asymmetry
      between the polar Cu2N and the vacuum gap breaks inversion symmetry in the alkali
      halide layer, inducing out-of-plane dipoles that are stabilized in one
      orientation (self-poling). The dipole orientation can be reversed by a critical
      electric field, producing sharp switching of the tunnel current passing through
      the junction.

PMID- 29062067
TI  - Alpha-1 antitrypsin augmentation therapy decreases miR-199a-5p, miR-598 and miR
      320a expression in monocytes via inhibition of NFkappaB.
AB  - Alpha-1 antitrypsin (AAT) augmentation therapy involves infusion of plasma
      purified AAT to AAT deficient individuals. Whether treatment affects microRNA
      expression has not been investigated. This study's objectives were to evaluate
      the effect of AAT augmentation therapy on altered miRNA expression in monocytes
      and investigate the mechanism. Monocytes were isolated from non-AAT deficient
      (MM) and AAT deficient (ZZ) individuals, and ZZs receiving AAT. mRNA (qRT-PCR,
      microarray), miRNA (miRNA profiling, qRT-PCR), and protein (western blotting)
      analyses were performed. Twenty one miRNAs were differentially expressed 3-fold
      between ZZs and MMs. miRNA validation studies demonstrated that in ZZ monocytes
      receiving AAT levels of miR-199a-5p, miR-598 and miR-320a, which are predicted to
      be regulated by NFkappaB, were restored to levels similar to MMs. Validated
      targets co-regulated by these miRNAs were reciprocally increased in ZZs receiving
      AAT in vivo and in vitro. Expression of these miRNAs could be increased in ZZ
      monocytes treated ex vivo with an NFkappaB agonist and decreased by NFkappaB
      inhibition. p50 and p65 mRNA and protein were significantly lower in ZZs
      receiving AAT than untreated ZZs. AAT augmentation therapy inhibits NFkappaB and
      decreases miR-199a-5p, miR-598 and miR-320a in ZZ monocytes. These NFkappaB
      inhibitory properties may contribute to the anti-inflammatory effects of AAT
      augmentation therapy.

PMID- 29062065
TI  - A chloroquine-induced macrophage-preconditioning strategy for improved
      nanodelivery.
AB  - Site-specific localization is critical for improving the therapeutic efficacy and
      safety of drugs. Nanoparticles have emerged as promising tools for localized drug
      delivery. However, over 90% of systemically injected nanocarriers typically
      accumulate in the liver and spleen due to resident macrophages that form the
      mononuclear phagocyte system. In this study, the clinically approved antimalarial
      agent chloroquine was shown to reduce nanoparticle uptake in macrophages by
      suppressing endocytosis. Pretreatment of mice with a clinically relevant dose of
      chloroquine substantially decreased the accumulation of liposomes and silicon
      particles in the mononuclear phagocyte system and improved tumoritropic and
      organotropic delivery. The novel use of chloroquine as a macrophage
      preconditioning agent presents a straightforward approach for addressing a major
      barrier in nanomedicine. Moreover, this priming strategy has broad applicability
      for improving the biodistribution and performance of particulate delivery
      systems. Ultimately, this study defines a paradigm for the combined use of
      macrophage-modulating agents with nanotherapeutics for improved site-specific
      delivery.

PMID- 29062068
TI  - Survey of electrically evoked responses in the retina - stimulus preferences and
      oscillation among neurons.
AB  - Electrical stimulation is an important tool in neuroscience research and
      clinically. In the retina, extensive work has revealed how the retinal ganglion
      cells respond to extracellular electrical stimulation. But little is known about
      the responses of other neuronal types, and more generally, how the network
      responds to stimulation. We conducted a survey of electrically evoked responses,
      over a range of pulse amplitudes and pulse widths, for 21 cell types spanning the
      inner two layers of the rabbit retina. It revealed: (i) the evoked responses of
      some neurons were charge insensitive; (ii) pulse-width sensitivity varied between
      cell types, allowing preferential recruitment of cell types; and (iii) 10-20 Hz
      damped oscillations across retinal layers. These oscillations were generated by
      reciprocal excitatory / inhibitory synapses, at locations as early as the cone
      horizontal-cell synapses. These results illustrate at cellular resolution how a
      network responds to extracellular stimulation, and could inform the development
      of bioelectronic implants for treating blindness.

PMID- 29062069
TI  - Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A
      complex.
AB  - The formation of paired helical filaments (PHF), which are composed of
      hyperphosphorylated Tau protein dissociating from microtubules, is one of the
      pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. The
      most important phosphatase that is capable of dephosphorylating Tau at AD
      specific phospho-sites is protein phosphatase 2 A (PP2A). Here we show that
      resveratrol, a polyphenol, significantly induces PP2A activity and reduces Tau
      phosphorylation at PP2A-dependent epitopes. The increase in PP2A activity is
      caused by decreased expression of the MID1 ubiquitin ligase that mediates
      ubiquitin-specific modification and degradation of the catalytic subunit of PP2A
      when bound to microtubules. Interestingly, we further show that MID1 expression
      is elevated in AD tissue. Our data suggest a key role of MID1 in the pathology of
      AD and related tauopathies. Together with previous studies showing that
      resveratrol reduces beta-amyloid toxicity they also give evidence of a promising
      role for resveratrol in the prophylaxis and therapy of AD.

PMID- 29062070
TI  - New opportunities for managing acute and chronic lung infections.
AB  - Lung diseases caused by microbial infections affect hundreds of millions of
      children and adults throughout the world. In Western populations, the treatment
      of lung infections is a primary driver of antibiotic resistance. Traditional
      therapeutic strategies have been based on the premise that the healthy lung is
      sterile and that infections grow in a pristine environment. As a consequence,
      rapid advances in our understanding of the composition of the microbiota of the
      skin and bowel have not yet been matched by studies of the respiratory tree. The
      recognition that the lungs are as populated with microorganisms as other mucosal
      surfaces provides the opportunity to reconsider the mechanisms and management of
      lung infections. Molecular analyses of the lung microbiota are revealing profound
      adverse responses to widespread antibiotic use, urbanization and globalization.
      This Opinion article proposes how technologies and concepts flowing from the
      Human Microbiome Project can transform the diagnosis and treatment of common lung
      diseases.

PMID- 29062073
TI  - Bacterial pathogenesis: Activating Helicobacter effector delivery.

PMID- 29062071
TI  - Anti-CRISPR: discovery, mechanism and function.
AB  - CRISPR-Cas adaptive immune systems are widespread among bacteria and archaea.
      Recent studies have shown that these systems have minimal long-term evolutionary
      effects in limiting horizontal gene transfer. This suggests that the ability to
      evade CRISPR-Cas immunity must also be widespread in phages and other mobile
      genetic elements. In this Progress article, we discuss recent discoveries that
      highlight how phages inactivate CRISPR-Cas systems by using anti-CRISPR proteins,
      and we outline evolutionary and biotechnological implications of their activity.

PMID- 29062074
TI  - Coherent Structure Formation through nonlinear interactions in 2D
      Magnetohydrodynamic Turbulence.
AB  - Using high resolution 2D magnetohydrodynamic (MHD) simulations we analyze the
      formation of coherent structures induced by nonlinear interactions in turbulent
      flows. The properties of these coherent structures, which at the smallest scales
      are identified through a spatial intermittent behavior, turn out to be guided by
      the conservation of ideal quadratic (rugged) invariants of the 2D incompressible
      MHD equations. Different spatial regions can be identified, where the
      correlations predicted using the variational principles associated to the rugged
      invariants are locally displayed. These local correlated structures are produced
      rapidly, as soon as the turbulence is fully developed. It is worth speculating
      that the small scale structures under our investigation could give rise to
      singular weak solutions when letting the dissipative coefficients go to zero. In
      this case their properties could furnish a key to understand which mathematical
      conditions characterize singularity emergency in weak solutions of the MHD ideal
      case.

PMID- 29062076
TI  - Computer-aided evaluation of the correlation between MRI morphology and
      immunohistochemical biomarkers or molecular subtypes in breast cancer.
AB  - Studies using tumor circularity (TC), a quantitative MRI morphologic index, to
      evaluate breast cancer are scarce. The purpose of this study is to evaluate the
      correlation between TC and immunohistochemical biomarkers or molecular subtypes
      in breast cancer. 146 patients with 150 breast cancers were selected. All tumors
      were confirmed by histopathology and examined by 3.0T MRI. TC was calculated by
      computer-aided software. The associations between TC and patient age, tumor size,
      histological grade, molecular subtypes, and immunohistochemical biomarkers
      including estrogen receptor (ER), progesterone receptor (PR), human epidermal
      growth factor receptor 2 (HER2), and Ki67 were analyzed. TC correlated inversely
      with tumor size (r = -0.224, P < 0.001), ER (r = -0.490, P < 0.001) and PR (r = 
      0.484, P < 0.001). However, TC correlated positively with Ki67 (r = 0.332, P <
      0.001) and histological grade (r = 0.309, P < 0.001). In multiple linear
      regression analysis, tumor size, ER, PR and Ki67 were independent influential
      factors of TC. Compared with HER2-overexpressed (61.6%), luminal A (54.7%) and
      luminal B (52.3%) subtypes, triple-negative breast cancer (TNBC) showed the
      highest score of TC (70.8%, P < 0.001). Our study suggests that TC can be used as
      an imaging biomarker to predict the aggressiveness of newly diagnosed breast
      cancers. TNBC seems to present as an orbicular appearance when comparing with
      other subtypes.

PMID- 29062075
TI  - Unraveling the roles of CD44/CD24 and ALDH1 as cancer stem cell markers in
      tumorigenesis and metastasis.
AB  - CD44/CD24 and ALDH1 are widely used cancer stem cell (CSC) markers in breast
      cancer. However, their expression is not always consistent even in the same
      subtype of breast cancer. Systematic comparison of their functions is still
      lacking. We investigated the expression of CD44, CD24 and ALDH1 in different
      subtypes of breast cancer cells, and explored their relationship with cancer
      progression. We defined a parameter CD44/CD24 ratio to present the expression
      level of CD44 and CD24 and found that high CD44/CD24 ratio and ALDH1+ are both
      indicators for cancer malignancy, but play different functions during tumor
      progression. High CD44/CD24 ratio is more related to cell proliferation and
      tumorigenesis, which is confirmed by mammosphere formation and tumorigenesis in
      xenotransplanted mice. ALDH1+ is a stronger indicator for cell migration and
      tumor metastasis. Suppression of CD44 and ALDH1 by siRNA led to decreased
      tumorigenicity and cell migration capacity. The combination of high CD44/CD24
      ratio and ALDH1+ would be a more reliable way to characterize CSCs. Moreover,
      both high CD44/CD24 ratio and ALDH1+ were conserved during metastasis, from the
      primary tumors to the circulating tumor cells (CTCs) and the distant metastases,
      suggesting the significant value of these CSC markers in assisting cancer
      detection, prognostic evaluation, and even cancer therapeutics.

PMID- 29062072
TI  - Development and regulation of single- and multi-species Candida albicans
      biofilms.
AB  - Candida albicans is among the most prevalent fungal species of the human
      microbiota and asymptomatically colonizes healthy individuals. However, it is
      also an opportunistic pathogen that can cause severe, and often fatal,
      bloodstream infections. The medical impact of C. albicans typically depends on
      its ability to form biofilms, which are closely packed communities of cells that
      attach to surfaces, such as tissues and implanted medical devices. In this
      Review, we provide an overview of the processes involved in the formation of C.
      albicans biofilms and discuss the core transcriptional network that regulates
      biofilm development. We also consider some of the advantages that biofilms
      provide to C. albicans in comparison with planktonic growth and explore
      polymicrobial biofilms that are formed by C. albicans and certain bacterial
      species.

PMID- 29062077
TI  - Long-lived laser-induced arc discharges for energy channeling applications.
AB  - Laser filamentation offers a promising way for the remote handling of large
      electrical power in the form of guided arc discharges. We here report that it is
      possible to increase by several orders of magnitude the lifetime of straight
      plasma channels from filamentation-guided sparks in atmospheric air. A 30 ms
      lifetime can be reached using a low-intensity, 100 mA current pulse. Stability of
      the plasma shape is maintained over such a timescale through a continuous Joule
      heating from the current. This paves the way for applications based on the
      generation of straight, long duration plasma channels, like virtual plasma
      antennas or contactless transfer of electric energy.

PMID- 29062079
TI  - The potential of Antheraea pernyi silk for spinal cord repair.
AB  - One of the most challenging applications for tissue regeneration is spinal cord
      damage. There is no cure for this, partly because cavities and scar tissue formed
      after injury present formidable barriers that must be crossed by axons to restore
      function. Natural silks are considered increasingly for medical applications
      because they are biocompatible, biodegradable and in selected cases promote
      tissue growth. Filaments from wild Antheraea pernyi silkworms can support axon
      regeneration in peripheral nerve injury. Here we presented evidence that degummed
      A. pernyi filaments (DAPF) support excellent outgrowth of CNS neurons in vitro by
      cell attachment to the high density of arginine-glycine-aspartic acid tripeptide
      present in DAPF. Importantly, DAPF showed stiffness properties that are well
      suited to spinal cord repair by supporting cell growth mechano-biology.
      Furthermore, we demonstrated that DAPF induced no activation of microglia, the
      CNS resident immune cells, either in vitro when exposed to DAPF or in vivo when
      DAPF were implanted in the cord. In vitro DAPF degraded gradually with a
      corresponding decrease in tensile properties. We conclude that A. pernyi silk
      meets the major biochemical and biomaterial criteria for spinal repair, and may
      have potential as a key component in combinatorial strategies for spinal repair.

PMID- 29062078
TI  - Design and evaluation of the immunogenicity and efficacy of a biomimetic
      particulate formulation of viral antigens.
AB  - Subunit viral vaccines are typically not as efficient as live attenuated or
      inactivated vaccines at inducing protective immune responses. This paper
      describes an alternative 'biomimetic' technology; whereby viral antigens were
      formulated around a polymeric shell in a rationally arranged fashion with a
      surface glycoprotein coated on to the surface and non-structural antigen and
      adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins
      formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted
      with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This
      Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner
      (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all
      inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant
      virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in
      both Vaccine-NP and IAV groups following the booster immunisation. IFN-gamma
      responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in
      both vaccinated groups. We observed that the protection afforded by the
      particulate vaccine was comparable to the licenced IAV formulation. In
      conclusion, the biomimetic particulates showed a promising immunogenicity and
      efficacy profile that may be improved by virtue of being a customisable mode of
      delivery.

PMID- 29062080
TI  - Mobile fluxons as coherent probes of periodic pinning in superconductors.
AB  - The interaction of (quasi)particles with a periodic potential arises in various
      domains of science and engineering, such as solid-state physics, chemical
      physics, and communication theory. An attractive test ground to investigate this
      interaction is represented by superconductors with artificial pinning sites,
      where magnetic flux quanta (Abrikosov vortices) interact with the pinning
      potential U(r) = U(r + R) induced by a nanostructure. At a combination of
      microwave and dc currents, fluxons act as mobile probes of U(r): The ac component
      shakes the fluxons in the vicinity of their equilibrium points which are
      unequivocally determined by the local pinning force counterbalanced by the
      Lorentz force induced by the dc current, linked to the curvature of U(r) which
      can then be used for a successful fitting of the voltage responses. A good
      correlation of the deduced dependences U(r) with the cross sections of the
      nanostructures points to that pinning is primarily caused by vortex length
      reduction. Our findings pave a new route to a non-destructive evaluation of
      periodic pinning in superconductor thin films. The approach should also apply to
      a broad class of systems whose evolution in time can be described by the coherent
      motion of (quasi)particles in a periodic potential.

PMID- 29062082
TI  - Temperature dependent thermal conductivity and transition mechanism in amorphous
      and crystalline Sb2Te3 thin films.
AB  - Sb2Te3 thin films are widely used in high density optical and electronic storage,
      high-resolution greyscale image recording, and laser thermal lithography. Thermal
      conductivity and its temperature dependence are critical factors that affect the
      application performance of thin films. This work aims to evaluate the temperature
      dependence of thermal conductivity of crystalline and amorphous Sb2Te3 thin films
      experimentally and theoretically, and explores into the corresponding mechanism
      of heat transport. For crystalline Sb2Te3 thin films, the thermal conductivity
      was found to be 0.35 +/- 0.035 W m-1 K-1 and showed weak temperature dependence.
      The thermal conductivity of amorphous Sb2Te3 thin films at temperatures below
      ~450 K is about 0.23 +/- 0.023 W m-1K-1, mainly arising from the lattice as the
      electronic contribution is negligible; at temperatures above 450 K, the thermal
      conductivity experiences an abrupt increase owing to the structural change from
      amorphous to crystalline state. The work can provide an important guide and
      reference to the real applications of Sb2Te3 thin films.

PMID- 29062081
TI  - An engineered vaccine of the Plasmodium vivax Duffy binding protein enhances
      induction of broadly neutralizing antibodies.
AB  - Plasmodium vivax invasion into human reticulocytes is a complex process. The
      Duffy binding protein (DBP) dimerization with its cognate receptor is vital for
      junction formation in the invasion process. Due to its functional importance, DBP
      is considered a prime vaccine candidate, but variation in B-cell epitopes at the
      dimer interface of DBP leads to induction of strain-limited immunity. We believe
      that the polymorphic residues tend to divert immune responses away from
      functionally conserved epitopes important for receptor binding or DBP
      dimerization. As a proof of concept, we engineered the vaccine DEKnull to ablate
      the dominant Bc epitope to partially overcome strain-specific immune antibody
      responses. Additional surface engineering on the next generation immunogen,
      DEKnull-2, provides an immunogenicity breakthrough to conserved protective
      epitopes. DEKnull-2 elicits a stronger broadly neutralizing response and
      reactivity with long-term persistent antibody responses of acquired natural
      immunity. By using novel engineered DBP immunogens, we validate that the prime
      targets of protective immunity are conformational epitopes at the dimer
      interface. These successful results indicate a potential approach that can be
      used generally to improve efficacy of other malaria vaccine candidates.

PMID- 29062083
TI  - The Subpolar North Atlantic Ocean Heat Content Variability and its Decomposition.
AB  - The Subpolar North Atlantic (SPNA) is one of the most important areas to global
      climate because its ocean heat content (OHC) is highly correlated with the
      Atlantic Meridional Overturning Circulation (AMOC), and its circulation strength
      affects the salt transport by the AMOC, which in turn feeds and sustains the
      strength of the AMOC. Moreover, the recent global surface warming "hiatus" may be
      attributed to the SPNA as one of the major planetary heat sinks. Although almost
      synchronized before 1996, the OHC has greater spatial disparities afterwards,
      which cannot be explained as driven by the North Atlantic Oscillation (NAO).
      Temperature decomposition reveals that the western SPNA OHC is mainly determined
      by the along isopycnal changes, while in the eastern SPNA along isopycnal changes
      and isopycnal undulation are both important. Further analysis indicates that heat
      flux dominates the western SPNA OHC, but in the eastern SPNA wind forcing affects
      the OHC significantly. It is worth noting that the along isopycnal OHC changes
      can also induce heaving, thus the observed heaving domination in global oceans
      cannot mask the extra heat in the ocean during the recent "hiatus".

PMID- 29062085
TI  - Physicochemical characterisation, immunogenicity and protective efficacy of a
      lead streptococcal vaccine: progress towards Phase I trial.
AB  - Globally, group A streptococcal infections are responsible for over 500,000
      deaths per year. A safe vaccine that does not induce autoimmune pathology and
      that affords coverage for most GAS serotypes is highly desired. We have
      previously demonstrated that a vaccine based on the conserved M-protein epitope,
      J8 was safe and immunogenic in a pilot Phase I study. We subsequently improved
      vaccine efficacy by incorporation of a B-cell epitope from the IL-8 protease,
      SpyCEP, which protected IL-8 and enhanced neutrophil ingress to the site of
      infection. We have now substituted the carrier protein, diphtheria toxoid with
      its superior analogue, CRM197 which provides better immunogenicity and is widely
      used in licenced human vaccines. The new vaccine was compared with the DT
      conjugate vaccine to confirm that these modifications have not altered the
      physicochemical properties of the vaccine. This vaccine, when tested in an animal
      model of GAS infection, demonstrated significant reduction in systemic and local
      GAS burden, with comparable efficacy to the DT conjugate vaccine. The vaccine was
      shown to be equally effective in the presence of human plasma and in the presence
      of pre-existing DT-specific antibodies, thus minimising concerns regarding its
      potential efficacy in humans.

PMID- 29062087
TI  - Predicted microbial secretomes and their target substrates in marine sediment.
AB  - Scientific drilling has identified a biosphere in marine sediments 1 , which
      contain many uncultivated microbial groups known only by their DNA sequences 2-4
      . Recycling of organic matter in sediments is an important component of
      biogeochemical cycles because marine sediments are critical for long-term carbon
      storage 5 . Turnover of carbon is hypothesized to be driven by the secretion of
      enzymes by microbial organisms 5-7 , which act to break down macromolecules into
      constitutive monomers that can be transported into cells. As such, the nature of
      the microbial secretome often influences the function of a community 6 . However,
      the microbial groups involved in this process and the biochemistry they encode is
      poorly understood. Here, we show that expressed genes from 5 to 159 meters below
      the seafloor 8 (mbsf) encode numerous candidate peptidases and carbohydrate
      active enzymes ('CAZymes') 9 targeted for secretion. The majority (90-99%) were
      assigned to Bacteria, of which 12% shared the highest sequence similarity with
      candidate phyla 10,11 . The remaining putatively secreted proteins shared highest
      sequence similarity with archaeal and fungal enzymes, which peak in two redox
      transition zones 12 . In the shallower redox zone at 30 mbsf, 20% of the
      transcripts encoding putative secreted peptidases were assigned to lineages
      7,13,14 of uncultivated Archaea. The target compounds of the predicted secreted
      proteome show a preference for necromass in the form of microbial cell envelopes
      as well as plankton and algal detritus. The predicted fungal secreted proteome
      encodes CAZymes not present in the predicted bacterial or archaeal secreted
      proteomes, indicating that fungi putatively play a minimal but specialized role
      in subseafloor carbohydrate recycling.

PMID- 29062084
TI  - Comparative Network Analysis of Patients with Non-Small Cell Lung Cancer and
      Smokers for Representing Potential Therapeutic Targets.
AB  - Cigarette smoking is the leading cause of lung cancer worldwide. In this study,
      we evaluated the serum autoantibody (AAb) repertoires of non-small cell lung
      cancer (NSCLC) patients and smokers (SM), leading to the identification of
      overactivated pathways and hubs involved in the pathogenesis of NSCLC. Surface-
      and solution-phase biopanning were performed on immunoglobulin G purified from
      the sera of NSCLC and SM groups. In total, 20 NSCLC- and 12 SM-specific peptides
      were detected, which were used to generate NSCLC and SM protein datasets. NSCLC-
      and SM-related proteins were visualized using STRING and Gephi, and their modules
      were analyzed using Enrichr. By integrating the overrepresented pathways such as
      pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL
      4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase
      D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the
      PLD pathway and inflammatory cytokines network as the most critical events in
      both groups, two super networks were made to elucidate new aspects of NSCLC
      pathogenesis and to determine the influence of cigarette smoking on tumour
      formation. Taken together, assessment of the AAb repertoires using a systems
      biology approach can delineate the hidden events involved in various disorders.

PMID- 29062086
TI  - Single nucleus sequencing reveals spermatid chromosome fragmentation as a
      possible cause of maize haploid induction.
AB  - Production of maternal haploids using a conspecific haploid inducer is routine
      and highly efficient in maize. However, the underlying mechanism of haploid
      induction (HI) is unclear. We develop a method to isolate three nuclei from a
      pollen grain and four microspores from a tetrad for whole-genome sequencing. A
      high rate of aneuploidy is observed at the three-nucleus stage (6/22 pollens)
      rather than at the tetrad stage (1/72 microspores) in one HI line CAU5. Frequent
      aneuploidy is also observed in another two inducer lines, but not in two regular
      lines, which implies that HI may be associated with pollen aneuploidy. We further
      sequence the individual embryos and endosperms of 88 maize kernels crossing
      between regular and inducer lines. Genome-wide elimination of the CAU5-derived
      chromosome is identified in eight of 81 embryos. Together, these results suggest
      that continuous chromosome fragmentation occurring post meiosis in the
      gametophyte may cause haploidy of the embryo.

PMID- 29062088
TI  - A CRISPR-Cas9-based gene drive platform for genetic interaction analysis in
      Candida albicans.
AB  - Candida albicans is the leading cause of fungal infections; yet, complex genetic
      interaction analysis remains cumbersome in this diploid pathogen. Here, we
      developed a CRISPR-Cas9-based 'gene drive array' platform to facilitate efficient
      genetic analysis in C. albicans. In our system, a modified DNA donor molecule
      acts as a selfish genetic element, replaces the targeted site and propagates to
      replace additional wild-type loci. Using mating-competent C. albicans haploids,
      each carrying a different gene drive disabling a gene of interest, we are able to
      create diploid strains that are homozygous double-deletion mutants. We generate
      double-gene deletion libraries to demonstrate this technology, targeting
      antifungal efflux and biofilm adhesion factors. We screen these libraries to
      identify virulence regulators and determine how genetic networks shift under
      diverse conditions. This platform transforms our ability to perform genetic
      interaction analysis in C. albicans and is readily extended to other fungal
      pathogens.

PMID- 29062089
TI  - No evidence of a cleaning mutualism between burying beetles and their phoretic
      mites.
AB  - Burying beetles (Nicrophorus vespilloides) breed on small vertebrate carcasses,
      which they shave and smear with antimicrobial exudates. Producing antimicrobials
      imposes a fitness cost on burying beetles, which rises with the potency of the
      antimicrobial defence. Burying beetles also carry phoretic mites (Poecilochirus
      carabi complex), which breed alongside them on the carcass. Here we test the
      novel hypothesis that P. carabi mites assist burying beetles in clearing the
      carcass of bacteria as a side-effect of grazing on the carrion. We manipulated
      the bacterial environment on carcasses and measured the effect on the beetle in
      the presence and absence of mites. With next-generation sequencing, we
      investigated how mites influence the bacterial communities on the carcass. We
      show that mites: 1) cause beetles to reduce the antibacterial activity of their
      exudates but 2) there are no consistent fitness benefits of breeding alongside
      mites. We also find that mites increase bacterial diversity and richness on the
      carcass, but do not reduce bacterial abundance. The current evidence does not
      support a cleaning mutualism between burying beetles and P. carabi mites, but
      more work is needed to understand the functional significance and fitness
      consequences for the beetle of mite-associated changes to the bacterial community
      on the carcass.

PMID- 29062090
TI  - Transcriptomics and proteomics reveal genetic and biological basis of superior
      biomass crop Miscanthus.
AB  - Miscanthus is a rhizomatous C4 grass which is considered as potential high
      yielding energy crop with the low-nutrient requirements, high water-use
      efficiency, and capability of C mitigation. To better understand the genetic
      basis, an integrative analysis of the transcriptome and proteome was performed to
      identify important genes and pathways involved in Miscanthus leaves. At the
      transcript level, 64,663 transcripts in M. lutarioriparius, 97,043 in M.
      sacchariflorus, 97,043 in M. sinensis, 67,323 in M. floridulus and 70,021 in M. *
      giganteus were detected by an RNA sequencing approach. At the protein level, 1964
      peptide-represented proteins were identified and 1933 proteins differed by 1.5
      fold or more in their relative abundance, as indicated by iTRAQ (isobaric tags
      for relative and absolute quantitation) analysis. Phylogenies were constructed
      from the nearly taxa of Miscanthus. A large number of genes closely related to
      biomass production were found. And SSR markers and their corresponding primers
      were derived from Miscanthus transcripts and 90% of them were successfully
      detected by PCR amplification among Miacanthus species. These similarities and
      variations on the transcriptional and proteomic level between Miscanthus species
      will serve as a resource for research in Miscanthus and other lignocellulose
      crops.

PMID- 29062091
TI  - Evidence of Reproductive Stress in Titanosaurian Sauropods Triggered by an
      Increase in Ecological Competition.
AB  - The occurrence of dinosaur pathologic eggs in the Late Cretaceous of Europe is
      well known, but their origin remains unclear. Here we expose the results of a
      detailed sampling of the conspicuous fossil record of Late Cretaceous
      titanosaurian eggs (oogenus Megaloolithius) from several southwestern Europe
      basins. After examining more than 450 samples, we observed a remarkable and
      statistically supported occurrence of multiple pathologic eggs in a relatively
      short stratigraphic range at the end of the early Maastrichtian, circa 71-70 Ma.
      All pathologic specimens exhibit multi-layered eggshell condition, a
      characteristic related to dystocia, or egg retention within the female uterus for
      an abnormal prolonged period of time. After exploring various scenarios, the
      occurrence of pathologic eggs is strongly correlated with an intense dinosaur
      faunal replacement that occurred during the early Maastrichtian in the Ibero
      Armorican Island. Given that inter-species competiveness is proved to produce
      major affects in ecological communities, our results suggest that pathologies in
      the eggs of European titanosaurians could be a consequence of an increase in
      reproductive stress triggered by direct ecological competition between different
      dinosaurs. Thus, the present study provides a new perspective of how dinosaurs
      might have been affected by ecological/environmental disturbance.

PMID- 29062092
TI  - Sliding of coherent twin boundaries.
AB  - Coherent twin boundaries (CTBs) are internal interfaces that can play a key role
      in markedly enhancing the strength of metallic materials while preserving their
      ductility. They are known to accommodate plastic deformation primarily through
      their migration, while experimental evidence documenting large-scale sliding of
      CTBs to facilitate deformation has thus far not been reported. We show here that
      CTB sliding is possible whenever the loading orientation enables the Schmid
      factors of leading and trailing partial dislocations to be comparable to each
      other. This theoretical prediction is confirmed by real-time transmission
      electron microscope experimental observations during uniaxial deformation of
      copper pillars with different orientations and is further validated at the atomic
      scale by recourse to molecular dynamics simulations. Our findings provide
      mechanistic insights into the evolution of plasticity in heavily twinned face
      centered cubic metals, with the potential for optimizing mechanical properties
      with nanoscale CTBs in material design.

PMID- 29062093
TI  - Photonics-based real-time ultra-high-range-resolution radar with broadband signal
      generation and processing.
AB  - Real-time and high-resolution target detection is highly desirable in modern
      radar applications. Electronic techniques have encountered grave difficulties in
      the development of such radars, which strictly rely on a large instantaneous
      bandwidth. In this article, a photonics-based real-time high-range-resolution
      radar is proposed with optical generation and processing of broadband linear
      frequency modulation (LFM) signals. A broadband LFM signal is generated in the
      transmitter by photonic frequency quadrupling, and the received echo is de
      chirped to a low frequency signal by photonic frequency mixing. The system can
      operate at a high frequency and a large bandwidth while enabling real-time
      processing by low-speed analog-to-digital conversion and digital signal
      processing. A conceptual radar is established. Real-time processing of an 8-GHz
      LFM signal is achieved with a sampling rate of 500 MSa/s. Accurate distance
      measurement is implemented with a maximum error of 4 mm within a range of ~3.5
      meters. Detection of two targets is demonstrated with a range-resolution as high
      as 1.875 cm. We believe the proposed radar architecture is a reliable solution to
      overcome the limitations of current radar on operation bandwidth and processing
      speed, and it is hopefully to be used in future radars for real-time and high
      resolution target detection and imaging.

PMID- 29062095
TI  - Elevated CO2 degassing rates prevented the return of Snowball Earth during the
      Phanerozoic.
AB  - The Cryogenian period (~720-635 Ma) is marked by extensive Snowball Earth
      glaciations. These have previously been linked to CO2 draw-down, but the severe
      cold climates of the Cryogenian have never been replicated during the Phanerozoic
      despite similar, and sometimes more dramatic changes to carbon sinks. Here we
      quantify the total CO2 input rate, both by measuring the global length of
      subduction zones in plate tectonic reconstructions, and by sea-level inversion.
      Our results indicate that degassing rates were anomalously low during the Late
      Neoproterozoic, roughly doubled by the Early Phanerozoic, and remained
      comparatively high until the Cenozoic. Our carbon cycle modelling identifies the
      Cryogenian as a unique period during which low surface temperature was more
      easily achieved, and shows that the shift towards greater CO2 input rates after
      the Cryogenian helped prevent severe glaciation during the Phanerozoic. Such a
      shift appears essential for the development of complex animal life.

PMID- 29062094
TI  - Genetic Variants Associated with Episodic Ataxia in Korea.
AB  - Episodic ataxia (EA) is a rare neurological condition characterized by recurrent
      spells of truncal ataxia and incoordination. Five genes (KCNA1, CACNA1A, CACNB4,
      SLC1A3, and UBR4) have been linked to EA. Despite extensive efforts to
      genetically diagnose EA, many patients remain still undiagnosed. Whole-exome
      sequencing was carried out in 39 Korean patients with EA to identify pathogenic
      mutations of the five known EA genes. We also evaluated 40 candidate genes that
      cause EA as a secondary phenotype or cerebellar ataxia. Eighteen patients (46%)
      revealed genetic information useful for establishing a molecular diagnosis of EA.
      In 11 patients, 16 pathogenic mutations were detected in three EA genes. These
      included nine mutations in CACNA1A, three in SLC1A3, and four in UBR4. Three
      patients had mutations in two genes, either CACNA1A and SLC1A3 or CACNA1A and
      UBR4, suggesting that SLC1A3 and UBR4 may act as genetic modifiers with synergic
      effects on the abnormal presynaptic activity caused by CACNA1A mutations. In
      seven patients with negative results for screening of EA genes, potential
      pathogenic mutations were identified in the candidate genes ATP1A2, SCN1A, TTBK2,
      TGM6, FGF14, and KCND3. This study demonstrates the genetic heterogeneity of
      Korean EA, and indicates that whole-exome sequencing may be useful for molecular
      genetic diagnosis of EA.

PMID- 29062096
TI  - Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis
      and Epidermal Structure.
AB  - The mammalian integumentary system plays important roles in body homeostasis, and
      dysfunction of melanogenesis or epidermal development may lead to a variety of
      skin diseases, including melanoma. Skin pigmentation in humans and coat color in
      fleece-producing animals are regulated by many genes. Among them, microphthalmia
      associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of
      the cascade and regulate activities of many important melanogenic enzymes. Here,
      we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an
      essential regulator of MITF and PAX3. Cdk5 knockdown in mice causes a lightened
      coat color, a polarized distribution of melanin and hyperproliferation of basal
      keratinocytes. Reduced expression of Keratin 10 (K10) resulting from Cdk5
      knockdown may be responsible for an abnormal epidermal structure. In contrast,
      overexpression of Cdk5 in sheep (Ovis aries) only produces brown patches on a
      white background, with no other observable abnormalities. Collectively, our
      findings show that Cdk5 has an important functional role in the regulation of
      melanin production and transportation and in normal development of the
      integumentary system.

PMID- 29062098
TI  - Optically induced metastability in Cu(In,Ga)Se2.
AB  - Cu(In,Ga)Se2 (CIGS) is presently the most efficient thin-film photovoltaic
      technology with efficiencies exceeding 22%. An important factor impacting the
      efficiency is metastability, where material changes occur over timescales of up
      to weeks during light exposure. A previously proposed (V Se -V Cu ) divacancy
      model presents a widely accepted explanation. We present experimental evidence
      for the optically induced metastability transition and expand the divacancy model
      with first-principles calculations. Using photoluminescence excitation
      spectroscopy, we identify a sub-bandgap optical transition that severely
      deteriorates the carrier lifetime. This is in accordance with the expanded
      divacancy model, which predicts that states below the conduction band are
      responsible for the metastability change. We determine the density-capture cross
      section product of the induced lifetime-limiting states and evaluate their impact
      on device performance. The experimental and theoretical findings presented can
      allow assessment of metastability characteristics of leading thin-film
      photovoltaic technologies.

PMID- 29062097
TI  - Altered surface mGluR5 dynamics provoke synaptic NMDAR dysfunction and cognitive
      defects in Fmr1 knockout mice.
AB  - Metabotropic glutamate receptor subtype 5 (mGluR5) is crucially implicated in the
      pathophysiology of Fragile X Syndrome (FXS); however, its dysfunction at the sub
      cellular level, and related synaptic and cognitive phenotypes are unexplored.
      Here, we probed the consequences of mGluR5/Homer scaffold disruption for mGluR5
      cell-surface mobility, synaptic N-methyl-D-aspartate receptor (NMDAR) function,
      and behavioral phenotypes in the second-generation Fmr1 knockout (KO) mouse.
      Using single-molecule tracking, we found that mGluR5 was significantly more
      mobile at synapses in hippocampal Fmr1 KO neurons, causing an increased synaptic
      surface co-clustering of mGluR5 and NMDAR. This correlated with a reduced
      amplitude of synaptic NMDAR currents, a lack of their mGluR5-activated long-term
      depression, and NMDAR/hippocampus dependent cognitive deficits. These synaptic
      and behavioral phenomena were reversed by knocking down Homer1a in Fmr1 KO mice.
      Our study provides a mechanistic link between changes of mGluR5 dynamics and
      pathological phenotypes of FXS, unveiling novel targets for mGluR5-based
      therapeutics.

PMID- 29062099
TI  - A Novel Visceral Adiposity Index for Prediction of Type 2 Diabetes and Pre
      diabetes in Chinese adults: A 5-year prospective study.
AB  - The Chinese visceral adiposity index (CVAI) is a recently developed indicator of
      visceral adiposity. We investigated the predictive value of the CVAI for the
      development of dysglycemia (pre-diabetes and type 2 diabetes) and compared its
      predictive power with that of the Visceral adiposity index (VAI) and various
      anthropometric indices. This community-based study included 2,383 participants.
      We assessed the predictive power of adiposity indices by performing univariate
      and multivariate binary logistic regression analysis and calculating the area
      under the receiver-operating characteristic (ROC) curve according to their
      quartiles. Logistic regression analysis showed that individuals in higher CVAI
      quartiles at baseline were more likely to develop dysglycemia than those in lower
      CVAI quartiles. The area under the ROC curve for CVAI was significantly higher
      than that of other adiposity indices. In addition, among the various adiposity
      indices tested, the CVAI had the greatest Youden index for identifying
      dysglycemia in both genders. Our data demonstrate that the CVAI is a better
      predictor of type 2 diabetes and pre-diabetes than the VAI, BMI, waist
      circumference, waist-to-hip ratio and waist-to-height ratio in Chinese adults.

PMID- 29062100
TI  - Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and
      rescues denervation-induced atrophy.
AB  - Exercise induces expression of the myokine irisin, which is known to promote
      browning of white adipose tissue and has been shown to mediate beneficial effects
      following exercise. Here we show that irisin induces expression of a number of
      pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic
      differentiation and myoblast fusion via activation of IL6 signaling. Injection of
      irisin in mice induces significant hypertrophy and enhances grip strength of
      uninjured muscle. Following skeletal muscle injury, irisin injection improves
      regeneration and induces hypertrophy. The effects of irisin on hypertrophy are
      due to activation of satellite cells and enhanced protein synthesis. In addition,
      irisin injection rescues loss of skeletal muscle mass following denervation by
      enhancing satellite cell activation and reducing protein degradation. These data
      suggest that irisin functions as a pro-myogenic factor in mice.

PMID- 29062101
TI  - One-step growth of multilayer-graphene hollow nanospheres via the self
      elimination of SiC nuclei templates.
AB  - We introduce a one-step growth method for producing multilayer-graphene hollow
      nanospheres via a high-temperature chemical vapor deposition process using
      tetramethylsilane as an organic precursor. When the SiC nuclei were grown under
      an excess carbon atmosphere, they were surrounded via desorption of the
      hydrocarbon gas species, and graphene layers formed on the surface of the SiC
      nuclei via the rearrangement of solid carbon during the heating and cooling. The
      core SiC nuclei were spontaneously removed by the subsequent thermal
      decomposition, which also supplied the carbon for the graphene layers. Hence,
      multilayer-graphene hollow nanospheres were acquired via a one-step process,
      which was simply controlled by the growth temperature. In this growth process,
      the SiC nuclei acted as both the template and carbon source for the formation of
      multilayer-graphene hollow nanospheres.

PMID- 29062102
TI  - Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin
      binding kinetics.
AB  - Cadherins are calcium dependent adhesion proteins that establish the
      intercellular mechanical contact by bridging the gap to adjacent cells.
      Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac
      desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic
      (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle
      disease. The molecular pathomechanisms of the vast majority of DSG2 mutations,
      however, are unknown. Here, we investigated the homophilic binding of wildtype
      Dsg2 and two mutations which are associated with ARVC. Using single molecule
      force spectroscopy and applying Jarzynski's equality we determined the kinetics
      and thermodynamics of Dsg2 homophilic binding. Notably, the free energy landscape
      of Dsg2 dimerization exposes a high activation barrier which is in line with the
      proposed strand-swapping binding motif. Although the binding motif is not
      directly affected by the mutations the binding kinetics differ significantly from
      the wildtype. Furthermore, we applied a dispase based cell dissociation assay
      using HT1080 cell lines over expressing Dsg2 wildtype and mutants, respectively.
      Our molecular and cellular results consistently demonstrate that Dsg2 mutations
      can heavily affect homophilic Dsg2 interactions. Furthermore, the full
      thermodynamic and kinetic description of Dsg2 dimerization provides a consistent
      model of the so far discussed homophilic cadherin binding.

PMID- 29062103
TI  - Recycled iron fuels new production in the eastern equatorial Pacific Ocean.
AB  - Nitrate persists in eastern equatorial Pacific surface waters because
      phytoplankton growth fueled by nitrate (new production) is limited by iron.
      Nitrate isotope measurements provide a new constraint on the controls of surface
      nitrate concentration in this region and allow us to quantify the degree and
      temporal variability of nitrate consumption. Here we show that nitrate
      consumption in these waters cannot be fueled solely by the external supply of
      iron to these waters, which occurs by upwelling and dust deposition. Rather, a
      substantial fraction of nitrate consumption must be supported by the recycling of
      iron within surface waters. Given plausible iron recycling rates, seasonal
      variability in nitrate concentration on and off the equator can be explained by
      upwelling rate, with slower upwelling allowing for more cycles of iron
      regeneration and uptake. The efficiency of iron recycling in the equatorial
      Pacific implies the evolution of ecosystem-level mechanisms for retaining iron in
      surface ocean settings where it limits productivity.

PMID- 29062104
TI  - Genomics of extreme ecological specialists: multiple convergent evolution but no
      genetic divergence between ecotypes of Maculinea alcon butterflies.
AB  - Biotic interactions are often acknowledged as catalysers of genetic divergence
      and eventual explanation of processes driving species richness. We address the
      question, whether extreme ecological specialization is always associated with
      lineage sorting, by analysing polymorphisms in morphologically similar ecotypes
      of the myrmecophilous butterfly Maculinea alcon. The ecotypes occur in either
      hygric or xeric habitats, use different larval host plants and ant species, but
      no significant distinctive molecular traits have been revealed so far. We apply
      genome-wide RAD-sequencing to specimens originating from both habitats across
      Europe in order to get a view of the potential evolutionary processes at work.
      Our results confirm that genetic variation is mainly structured geographically
      but not ecologically - specimens from close localities are more related to each
      other than populations of each ecotype from distant localities. However, we found
      two loci for which the association with xeric versus hygric habitats is supported
      by segregating alleles, suggesting convergent evolution of habitat preference.
      Thus, ecological divergence between the forms probably does not represent an
      early stage of speciation, but may result from independent recurring adaptations
      involving few genes. We discuss the implications of these results for
      conservation and suggest preserving biotic interactions and main genetic
      clusters.

PMID- 29062105
TI  - Resection of high frequency oscillations predicts seizure outcome in the
      individual patient.
AB  - High frequency oscillations (HFOs) are recognized as biomarkers for epileptogenic
      brain tissue. A remaining challenge for epilepsy surgery is the prospective
      classification of tissue sampled by individual electrode contacts. We analysed
      long-term invasive recordings of 20 consecutive patients who subsequently
      underwent epilepsy surgery. HFOs were defined prospectively by a previously
      validated, automated algorithm in the ripple (80-250 Hz) and the fast ripple (FR,
      250-500 Hz) frequency band. Contacts with the highest rate of ripples co
      occurring with FR over several five-minute time intervals designated the HFO
      area. The HFO area was fully included in the resected area in all 13 patients who
      achieved seizure freedom (specificity 100%) and in 3 patients where seizures
      reoccurred (negative predictive value 81%). The HFO area was only partially
      resected in 4 patients suffering from recurrent seizures (positive predictive
      value 100%, sensitivity 57%). Thus, the resection of the prospectively defined
      HFO area proved to be highly specific and reproducible in 13/13 patients with
      seizure freedom, while it may have improved the outcome in 4/7 patients with
      recurrent seizures. We thus validated the clinical relevance of the HFO area in
      the individual patient with an automated procedure. This is a prerequisite before
      HFOs can guide surgical treatment in multicentre studies.

PMID- 29062106
TI  - Toxoplasma-induced changes in host risk behaviour are independent of parasite
      derived AaaH2 tyrosine hydroxylase.
AB  - Toxoplasma gondii infects a broad range of hosts and can establish chronic
      infections with the formation of brain cysts. Infected animals show altered risk
      behaviour which has been suggested to increase capture probability of hosts, and
      thus enhance parasite transmission. It has been proposed that the ability of
      Toxoplasma cysts to secrete tyrosine hydroxylase could mediate these behavioural
      alterations. We tested the involvement of secreted tyrosine hydroxylase, coded by
      the parasite AaaH2 gene, in the development of alterations in mouse behaviour, by
      generating an AaaH2 deletion mutant parasite strain and testing its influence on
      behaviour. We found that both mice infected with wild type or AaaH2 mutant
      strains showed changes in risk behaviour. We confirmed these findings using
      factor analysis of the behaviour, which revealed that behavioural changes
      happened along a single dimension, and were observed in both infected groups.
      Furthermore, we developed a new behavioural paradigm in which animals are
      unpredictably trapped, and observed that both groups of infected animals perceive
      trapping but fail to adjust their behaviour to avoid further trapping. These
      results demonstrate that parasite-secreted AaaH2 TH is neither necessary for the
      generation of risky behaviour nor for the increased trappability observed during
      chronic Toxoplasma infection.

PMID- 29062107
TI  - Tunable two-dimensional assembly of colloidal particles in rotating electric
      fields.
AB  - Tunable interparticle interactions in colloidal suspensions are of great interest
      because of their fundamental and practical significance. In this paper we present
      a new experimental setup for self-assembly of colloidal particles in two
      dimensional systems, where the interactions are controlled by external rotating
      electric fields. The maximal magnitude of the field in a suspension is 25 V/mm,
      the field homogeneity is better than 1% over the horizontal distance of 250 MUm,
      and the rotation frequency is in the range of 40 Hz to 30 kHz. Based on numerical
      electrostatic calculations for the developed setup with eight planar electrodes,
      we found optimal experimental conditions and performed demonstration experiments
      with a suspension of 2.12 MUm silica particles in water. Thanks to its
      technological flexibility, the setup is well suited for particle-resolved studies
      of fundamental generic phenomena occurring in classical liquids and solids, and
      therefore it should be of interest for a broad community of soft matter,
      photonics, and material science.

PMID- 29062108
TI  - Ionic liquid-based dispersive liquid-liquid microextraction combined with
      functionalized magnetic nanoparticle solid-phase extraction for determination of
      industrial dyes in water.
AB  - N-butyl pyridinium bis((trifluoromethyl)sulfonyl)imide ([Hpy]NTf2) functionalized
      core/shell magnetic nanoparticles (MNPs, Fe3O4@SiO2@[Hpy]NTf2)) were prepared and
      applied as an adsorbent for magnetic solid phase extraction (MSPE) of three
      commonly used industrial dyes including malachite green, crystal violet and
      methylene blue. Extraction solution was mixed with 100 mg extraction material of
      Fe3O4@SiO2@[Hpy]NTf2, and 1 mL of acetonitrile was used to elute target analytes
      for further extraction and purification. [Hpy]NTf2 was used as extraction
      solution, and 500 MUL methanol was selected as dispersive solvent in ionic liquid
      (IL) dispersive liquid-liquid microextraction (DLLME) method. After sonication
      for 5 min and centrifugation at 447 g for 10 min, 20 MUL of sedimented phase was
      injected into HPLC-UV system. The limit of detection (LOD) and limit of
      quantification (LOQ) of current method were 0.03 and 0.16 MUg.L-1, respectively,
      which indicated the sensitivity was comparable or even superior to other reported
      methods. The relative recoveries of the target analytes ranged from 86.1% to
      100.3% with relative standard deviations between 0.3% and 4.5%. The developed
      method has been successfully applied to determine the level of three industrial
      dyes in different water samples.

PMID- 29062110
TI  - High-frequency, low-coverage "false positives" mutations may be true in GS Junior
      sequencing studies.
AB  - The GS Junior sequencer provides simplified procedures for library preparation
      and data processing. Errors in pyrosequencing generate some biases during library
      construction and emulsion PCR amplification. False-positive mutations are
      identified by related characteristics described in the manufacturer's manual, and
      some detected mutations may have 'borderline' characteristics when they are
      detected in few reads or at low frequency. Among these mutations, however, some
      may be true positives. This study aimed to improve the accuracy of identifying
      true positives among mutations with borderline false-positive characteristics
      detected with GS Junior sequencing. Mutations with the borderline features were
      tested for validity with Sanger sequencing. We examined 10 mutations detected in
      coverages <20-fold at frequencies >30% (group A) and 16 mutations detected in
      coverages >20-fold at frequencies < 30% (group B). In group A, two mutations were
      not confirmed, and two mutations with 100% frequency were confirmed as
      heterozygous alleles. No mutation in group B was confirmed. The two groups had
      significantly different false-positive prevalences (p = 0.001). These results
      suggest that mutations detected at frequencies less than 30% can be confidently
      identified as false-positives but that mutations detected at frequencies over
      30%, despite coverages less than 20-fold, should be verified with Sanger
      sequencing.

PMID- 29062109
TI  - Sensing and responding to allergic response cytokines through a genetically
      encoded circuit.
AB  - While constantly rising, the prevalence of allergies is globally one of the
      highest among chronic diseases. Current treatments of allergic diseases include
      the application of anti-histamines, immunotherapy, steroids, and anti
      immunoglobulin E (IgE) antibodies. Here we report mammalian cells engineered with
      a synthetic signaling cascade able to monitor extracellular pathophysiological
      levels of interleukin 4 and interleukin 13, two main cytokines orchestrating
      allergic inflammation. Upon activation of transgenic cells by these cytokines,
      designed ankyrin repeat protein (DARPin) E2_79, a non-immunogenic protein binding
      human IgE, is secreted in a precisely controlled and reversible manner. Using
      human whole blood cell culturing, we demonstrate that the mammalian dual T helper
      2 cytokine sensor produces sufficient levels of DARPin E2_79 to dampen histamine
      release in allergic subjects exposed to allergens. Hence, therapeutic gene
      networks monitoring disease-associated cytokines coupled with in situ production,
      secretion and systemic delivery of immunomodulatory biologics may foster advances
      in the treatment of allergies.

PMID- 29062111
TI  - Differential effects of speech situations on mothers' and fathers' infant
      directed and dog-directed speech: An acoustic analysis.
AB  - There is growing evidence that dog-directed and infant-directed speech have
      similar acoustic characteristics, like high overall pitch, wide pitch range, and
      attention-getting devices. However, it is still unclear whether dog- and infant
      directed speech have gender or context-dependent acoustic features. In the
      present study, we collected comparable infant-, dog-, and adult directed speech
      samples (IDS, DDS, and ADS) in four different speech situations (Storytelling,
      Task solving, Teaching, and Fixed sentences situations); we obtained the samples
      from parents whose infants were younger than 30 months of age and also had pet
      dog at home. We found that ADS was different from IDS and DDS, independently of
      the speakers' gender and the given situation. Higher overall pitch in DDS than in
      IDS during free situations was also found. Our results show that both parents
      hyperarticulate their vowels when talking to children but not when addressing
      dogs: this result is consistent with the goal of hyperspeech in language
      tutoring. Mothers, however, exaggerate their vowels for their infants under 18
      months more than fathers do. Our findings suggest that IDS and DDS have context
      dependent features and support the notion that people adapt their prosodic
      features to the acoustic preferences and emotional needs of their audience.

PMID- 29062112
TI  - Association between post-transplant red cell distribution width and prognosis of
      kidney transplant recipients.
AB  - The role of elevated post-transplant red cell distribution width (RDW) as a
      predictive factor for graft loss remains unclear, although RDW was reported to be
      significantly associated with poor prognosis in various clinical fields. We
      performed a retrospective cohort study with 2,939 kidney transplant patients from
      two tertiary teaching hospitals in Korea. RDW level at transplantation and 3
      months post-transplantation were collected. Those with RDW in the upper quartile
      range were considered to have increased RDW (>14.9%). Death-with-graft-function
      (DWGF), death-censored graft failure (DCGF), and composite graft loss were
      assessed as the study outcomes, using multivariable cox proportional hazard
      model. At the median follow-up duration of 6.6 (3.6-11.4) years, 336 patients
      experienced graft loss. There were 679 patients with elevated RDW at 3-months
      post-transplant. Elevated RDW was associated with composite graft loss (adjusted
      hazard ratio, 1.60, 95% confidence interval, 1.23-2.07, P < 0.001), even after
      adjusted for hemoglobin and various clinical factors. The 1% increment of post
      transplant RDW was also significantly associated with the outcome, regardless of
      the presence of anemia. The worst prognosis was seen in patients with elevated
      RDW after transplantation, but not at baseline. Therefore, post-transplant RDW
      level may be significantly associated with patient prognosis, independent of
      hemoglobin values.

PMID- 29062113
TI  - Active modulation of the calcifying fluid carbonate chemistry (delta11B, B/Ca)
      and seasonally invariant coral calcification at sub-tropical limits.
AB  - Coral calcification is dependent on both the supply of dissolved inorganic carbon
      (DIC) and the up-regulation of pH in the calcifying fluid (cf). Using geochemical
      proxies (delta11B, B/Ca, Sr/Ca, Li/Mg), we show seasonal changes in the pHcf and
      DICcf for Acropora yongei and Pocillopora damicornis growing in-situ at Rottnest
      Island (32 degrees S) in Western Australia. Changes in pHcf range from 8.38 in
      summer to 8.60 in winter, while DICcf is 25 to 30% higher during summer compared
      to winter (*1.5 to *2 seawater). Thus, both variables are up-regulated well above
      seawater values and are seasonally out of phase with one another. The net effect
      of this counter-cyclical behaviour between DICcf and pHcf is that the aragonite
      saturation state of the calcifying fluid (Omegacf) is elevated ~4 times above
      seawater values and is ~25 to 40% higher during winter compared to summer. Thus,
      these corals control the chemical composition of the calcifying fluid to help
      sustain near-constant year-round calcification rates, despite a seasonal seawater
      temperature range from just ~19 degrees  to 24  degrees C. The ability of corals
      to up-regulate Omegacf is a key mechanism to optimise biomineralization, and is
      thus critical for the future of coral calcification under high CO2 conditions.

PMID- 29062114
TI  - Bioprospecting on invasive plant species to prevent seed dispersal.
AB  - ABSRACT: The most anthropized regions of the world are characterized by an
      impressive abundance of invasive plants, which alter local biodiversity and
      ecosystem services. An alternative strategy to manage these species could be
      based on the exploitation of their fruits in a framework of bioprospecting to
      obtain high-added value compounds or phytocomplexes that are useful for humans.
      Here we tested this hypothesis on three invasive plants (Lonicera japonica
      Thunb., Phytolacca americana L., and Prunus serotina Ehrh.) in the Po plain
      (northern Italy) which bear fruits that are highly consumed by frugivorous birds
      and therefore dispersed over large distances. Our biochemical analyses revealed
      that unripe fruit shows high antioxidant properties due to the presence of
      several classes of polyphenols, which have a high benchmark value on the market.
      Fruit collection for phytochemical extraction could really prevent seed dispersal
      mediated by frugivorous animals and produce economic gains to support local
      management actions.

PMID- 29062115
TI  - A self-feedback network based on liquid chromatography-quadrupole-time of flight
      mass spectrometry for system identification of beta-carboline alkaloids in
      Picrasma quassioides.
AB  - Profiling chemical components in herbs by mass spectrometry is a challenging work
      because of the lack of standard compounds, especially for position isomers. This
      paper provides a strategy based on a self-feedback network of mass spectra (MS)
      data to identify chemical constituents in herbs by liquid chromatography
      quadrupole-time of flight mass spectrometry without compound standards.
      Components sharing same skeleton were screened and all ions were classified into
      a database. All candidates were connected by the selected bridging ions to
      establish a primary MS network. Benefited from such a network, it is feasible to
      characterize sequentially the structures of all diagnostic ions and candidates
      once single component has been de novo identified. Taking Picrasma quassioides as
      an example, the primary network of beta-carbolines was established with 65 ions
      (selected from 76 beta-carbolines), each of which appeared at least in four
      compounds. Once an alkaloid has been identified, its logical ions could feedback
      into primary network to build pathways with other unknown compounds. Moreover,
      the position of the substituent groups could be deduced through the secondary
      metabolic pathways of alkaloids (plant secondary metabolism). The network
      therefore can be utilized for identification of unknown compounds and even their
      position isomers.

PMID- 29062116
TI  - Facile synthesis and emission enhancement in NaLuF4 upconversion nano/micro
      crystals via Y3+ doping.
AB  - A series of Y3+-absent/doped NaLuF4:Yb3+, Tm3+ nano/micro-crystals were prepared
      via a hydrothermal process with the assistance of citric acid. Cubic nanospheres,
      hexagonal microdisks, and hexagonal microprisms can be achieved by simply
      adjusting the reaction temperature. The effect of Y3+ doping on the morphology
      and upconversion (UC) emission of the as-prepared samples were systematically
      investigated. Compared to their Y3+-free counterpart, the integrated spectral
      intensities in the range of 445-495 nm from alpha-, beta-, and alpha/beta-mixed
      NaLuF4:Yb3+, Tm3+ crystals with 40 mol% Y3+ doping are increased by 9.7, 4.4, and
      24.3 times, respectively; red UC luminescence intensities in the range of 630-725
      nm are enhanced by 4.6, 2.4, and 24.9 times, respectively. It is proposed that
      the increased UC emission intensity is mainly ascribed to the deformation of
      crystal lattice, due to the electron cloud distortion in host lattice after Y3+
      doping. This paper provides a facile route to achieve nano/micro-structures with
      intense UC luminescence, which may have potential applications in optoelectronic
      devices.

PMID- 29062117
TI  - Phenotypic Innovation and Adaptive Constraints in the Evolutionary Radiation of
      Palaeozoic Crinoids.
AB  - To better understand the patterns and processes shaping large-scale phenotypic
      diversification, I integrate palaeobiological and phylogenetic perspectives to
      investigate a ~200-million-year radiation using a global sample of Palaeozoic
      crinoid echinoderms. Results indicate the early history of crinoid
      diversification is characterized by early burst dynamics with decelerating
      morphologic rates. However, in contrast with expectation for a single "early
      burst" model, morphospace continued to expand following a slowdown in rates. In
      addition, I find evidence for an isolated peak in morphologic rates occurring
      late in the clade's history. This episode of elevated rates is not associated
      with increased disparity, morphologic novelty, or the radiation of a single
      subclade. Instead, this episode of elevated rates involved multiple subclade
      radiations driven by environmental change toward a pre-existing adaptive optimum.
      The decoupling of morphologic disparity with rates of change suggests phenotypic
      rates are primarily shaped by ecologic factors rather than the origination of
      morphologic novelty alone. These results suggest phenotypic diversification is
      far more complex than models commonly assumed in comparative biology.
      Furthermore, palaeontological disparity patterns are not a reliable proxy for
      rates after an initial diversifying phase. These issues highlight the need for
      continued synthesis between fossil and phylogenetic approaches to macroevolution.

PMID- 29062118
TI  - Propensity-score-matched evaluation of the incidence of radiation pneumonitis and
      secondary cancer risk for breast cancer patients treated with IMRT/VMAT.
AB  - Propensity score matching evaluates the treatment incidence of radiation-induced
      pneumonitis (RP) and secondary cancer risk (SCR) after intensity-modulated
      radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for breast cancer
      patients. Of 32 patients treated with IMRT and 58 who received VMAT were
      propensity matched in a 1:1 ratio. RP and SCR were evaluated as the endpoints of
      acute and chronic toxicity, respectively. Self-fitted normal tissue complication
      probability (NTCP) parameter values were used to analyze the risk of RP. SCRs
      were evaluated using the preferred Schneider's parameterization risk models. The
      dosimetric parameter of the ipsilateral lung volume receiving 40 Gy (IV40) was
      selected as the dominant risk factor for the RP NTCP model. The results showed
      that the risks of RP and NTCP, as well as that of SCR of the ipsilateral lung,
      were slightly lower than the values in patients treated with VMAT versus IMRT (p
      <= 0.01). However, the organ equivalent dose and excess absolute risk values in
      the contralateral lung and breast were slightly higher with VMAT than with IMRT
      (p <= 0.05). When compared to IMRT, VMAT is a rational radiotherapy option for
      breast cancer patients, based on its reduced potential for inducing secondary
      malignancies and RP complications.

PMID- 29062119
TI  - Effects of glucose concentration on 1,18-cis-octadec-9-enedioic acid
      biotransformation efficiency and lipid body formation in Candida tropicalis.
AB  - The unsaturated long-chain alpha,omega-dicarboxylic acid 1,18-cis-octadec-9
      enedioic acid (cis-ODA) is a versatile precursor of various valuable compounds,
      such as polymers, and can be obtained from renewable resources. This makes cis
      ODA highly attractive for the chemical industry where there is a growing interest
      in sustainable processes. However, chemical synthesis of the cis isomers is
      currently not feasible. In contrast, biotechnological production allows for
      highly specific and selective reactions. Therefore, we developed an efficient
      production strategy for cis-ODA using Candida tropicalis as a whole-cell
      biocatalyst for the biotransformation of oleic acid, which naturally occurs in
      various fats and oils. Applying a bench-top system comprising eight parallel
      bioreactors, the production process was characterised and optimised for high
      productivity. Glucose feed rate was identified as the most crucial process
      parameter influencing product yield, with high rates inducing oleic acid
      incorporation into triacylglycerols and storage in lipid bodies. Conversely,
      application of medium-chain length fatty acid as a substrate did not show any
      occurrence of lipid bodies. Applying the lowest possible molar ratio of glucose
      to oleic acid (1.5) resulted in marginal lipid body formation, but led to a peak
      volumetric productivity of 0.56 g/L/h and a final titre of approximately 45 g/L
      with a corresponding yield of 70%.

PMID- 29062120
TI  - Biota turnovers from phylogenies.

PMID- 29062121
TI  - Sequence entropy of folding and the absolute rate of amino acid substitutions.
AB  - Adequate representations of protein evolution should consider how the acceptance
      of mutations depends on the sequence context in which they arise. However,
      epistatic interactions among sites in a protein result in hererogeneities in the
      substitution rate, both temporal and spatial, that are beyond the capabilities of
      current models. Here we use parallels between amino acid substitutions and
      chemical reaction kinetics to develop an improved theory of protein evolution. We
      constructed a mechanistic framework for modelling amino acid substitution rates
      that uses the formalisms of statistical mechanics, with principles of population
      genetics underlying the analysis. Theoretical analyses and computer simulations
      of proteins under purifying selection for thermodynamic stability show that
      substitution rates and the stabilization of resident amino acids (the
      'evolutionary Stokes shift') can be predicted from biophysics and the effect of
      sequence entropy alone. Furthermore, we demonstrate that substitutions
      predominantly occur when epistatic interactions result in near neutrality;
      substitution rates are determined by how often epistasis results in such nearly
      neutral conditions. This theory provides a general framework for modelling
      protein sequence change under purifying selection, potentially explains patterns
      of convergence and mutation rates in real proteins that are incompatible with
      previous models, and provides a better null model for the detection of adaptive
      changes.

PMID- 29062122
TI  - Frugivory-related traits promote speciation of tropical palms.
AB  - Animal-mediated seed dispersal by frugivorous birds and mammals is central to the
      ecology and functioning of ecosystems, but whether and how frugivory-related
      traits have affected plant speciation remains little explored. Fruit size is
      directly linked to plant dispersal capacity and therefore influences gene flow
      and genetic divergence of plant populations. Using a global species-level
      phylogeny with comprehensive data on fruit sizes and plant species distributions,
      we test whether fruit size has affected speciation rates of palms (Arecaceae), a
      plant family characteristic of tropical rainforests. Globally, the results reveal
      that palms with small fruit sizes have increased speciation rates compared with
      those with large (megafaunal) fruits. Speciation of small-fruited palms is
      particularly high in the understory of tropical rainforests in the New World, and
      on islands in the Old World. This suggests that frugivory-related traits in
      combination with geography and the movement behaviour of frugivores can influence
      the speciation of fleshy-fruited plants.

PMID- 29062124
TI  - Self-regulation and the stability of large ecological networks.
AB  - The stability of complex ecological networks depends both on the interactions
      between species and the direct effects of the species on themselves. These self
      effects are known as 'self-regulation' when an increase in a species' abundance
      decreases its per-capita growth rate. Sources of self-regulation include
      intraspecific interference, cannibalism, time-scale separation between consumers
      and their resources, spatial heterogeneity and nonlinear functional responses
      coupling predators with their prey. The influence of self-regulation on network
      stability is understudied and in addition, the empirical estimation of self
      effects poses a formidable challenge. Here, we show that empirical food web
      structures cannot be stabilized unless the majority of species exhibit
      substantially strong self-regulation. We also derive an analytical formula
      predicting the effect of self-regulation on network stability with high accuracy
      and show that even for random networks, as well as networks with a cascade
      structure, stability requires negative self-effects for a large proportion of
      species. These results suggest that the aforementioned potential mechanisms of
      self-regulation are probably more important in contributing to the stability of
      observed ecological networks than was previously thought.

PMID- 29062125
TI  - Thermal limits to the geographic distributions of shallow-water marine species.
AB  - Temperature profoundly affects species' geographic ranges, but the extent to
      which it limits contemporary range edges has been difficult to assess from
      laboratory experiments of thermal tolerance. The persistence of populations
      depends on temperature-mediated outcomes of ecological and demographic processes
      across all stages of a species' life history, as well as any adaptation to local
      temperature regimes. We assessed the relationships between sea temperature and
      observed distributional ranges for 1,790 shallow-water marine species from 10
      animal classes and found remarkable consistencies in trends in realized thermal
      limits among taxa and ocean basins, as well as general agreement with previous
      laboratory findings. Realized thermal niches increase from the Equator towards
      cold-temperate locations, despite an opposite trend in geographic range size.
      Species' cool distribution limits are best predicted by the magnitude of
      seasonality within their range, while a relatively firm thermal barrier exists on
      the equatorward range edge for temperate species. Our findings of consistencies
      in realized thermal limits indicate potential limits to adaptation among common
      marine species and highlight the value of realized thermal niches for predicting
      species' distributional dynamics in warming seas.

PMID- 29062123
TI  - Biocultural approaches to well-being and sustainability indicators across scales.
AB  - Monitoring and evaluation are central to ensuring that innovative, multi-scale,
      and interdisciplinary approaches to sustainability are effective. The development
      of relevant indicators for local sustainable management outcomes, and the ability
      to link these to broader national and international policy targets, are key
      challenges for resource managers, policymakers, and scientists. Sets of
      indicators that capture both ecological and social-cultural factors, and the
      feedbacks between them, can underpin cross-scale linkages that help bridge local
      and global scale initiatives to increase resilience of both humans and
      ecosystems. Here we argue that biocultural approaches, in combination with
      methods for synthesizing across evidence from multiple sources, are critical to
      developing metrics that facilitate linkages across scales and dimensions.
      Biocultural approaches explicitly start with and build on local cultural
      perspectives - encompassing values, knowledges, and needs - and recognize
      feedbacks between ecosystems and human well-being. Adoption of these approaches
      can encourage exchange between local and global actors, and facilitate
      identification of crucial problems and solutions that are missing from many
      regional and international framings of sustainability. Resource managers,
      scientists, and policymakers need to be thoughtful about not only what kinds of
      indicators are measured, but also how indicators are designed, implemented,
      measured, and ultimately combined to evaluate resource use and well-being. We
      conclude by providing suggestions for translating between local and global
      indicator efforts.

PMID- 29062126
TI  - Phylogenetic evidence for mid-Cenozoic turnover of a diverse continental biota.
AB  - Rapid climatic change at the beginning of the Oligocene epoch is concordant with
      global biotic turnover in the fossil record. However, while Southern Hemisphere
      geological movement played a key role in shaping these global climatic shifts,
      given generally poor terrestrial fossil records, evidence for matching turnover
      in entire Austral biotas is lacking. Emerging comprehensive phylogenetic
      frameworks provide alternative avenues to explore for signals of mass turnover or
      restructuring. Here, we combine phylogenetic data with empirical and simulation
      based approaches to understand the temporal dynamics of the origins of a diverse
      and highly endemic continental biota (Australian lizards and snakes). These
      analyses indicate that the temporal clustering of major radiation ages in
      Gondwanan endemic lineages and immigration into Australia is narrower than
      expected under time-continuous models assuming no overarching external
      perturbation. Independent phylogenetic dating analyses further indicate that the
      timing of both processes is concentrated in the period post-dating the Eocene
      Oligocene transition (~34 million years ago). Epoch-defining processes around the
      start of the Oligocene appear to have also played a decisive role in reshaping a
      diverse Southern Hemisphere biota-by both re-setting Gondwanan endemic diversity
      and opening the way to successful immigration from the north.

PMID- 29062127
TI  - Graphene oxide electrodeposited electrode enhances start-up and selective
      enrichment of exoelectrogens in bioelectrochemical systems.
AB  - This study seeks to assess the impact that the anodic electrodeposition of
      graphene oxide (GO) has on the start-up process and on the development of
      microbial communities on the anode of BESs. The GO electrodeposited electrodes
      were characterised in abiotic conditions to verify the extent of the modification
      and were then transferred to a bioelectrochemical reactor. Results showed that
      the modified electrode allowed for a reduced start-up time compared to the
      control electrode. After three months, high throughput sequencing was performed,
      revealing that electrochemically reduced graphene oxide acts as a selective agent
      toward exoelectrogenic bacteria as Geobacter. Overall, this study shows that GO
      modified electrodes enhance biofilm build up in BES.

PMID- 29062128
TI  - Spatial Heterogeneity of SOM Concentrations Associated with White-rot Versus
      Brown-rot Wood Decay.
AB  - White- and brown-rot fungal decay via distinct pathways imparts characteristic
      molecular imprints on decomposing wood. However, the effect that a specific wood
      rotting type of fungus has on proximal soil organic matter (SOM) accumulation
      remains unexplored. We investigated the potential influence of white- and brown
      rot fungi-decayed Abies nephrolepis logs on forest SOM stocks (i.e., soil total
      carbon (C) and nitrogen (N)) and the concentrations of amino sugars (microbial
      necromass) at different depths and horizontal distances from decaying woody
      debris. The brown-rot fungal wood decay resulted in higher concentrations of soil
      C and N and a greater increase in microbial necromass (i.e., 1.3- to 1.7-fold
      greater) than the white-rot fungal wood decay. The white-rot sets were
      accompanied by significant differences in the proportions of the bacterial
      residue index (muramic acid%) with soil depth; however, the brown-rot-associated
      soils showed complementary shifts, primarily in fungal necromass, across
      horizontal distances. Soil C and N concentrations were significantly correlated
      with fungal rather than bacterial necromass in the brown-rot systems. Our
      findings confirmed that the brown-rot fungi-dominated degradation of
      lignocellulosic residues resulted in a greater SOM buildup than the white-rot
      fungi-dominated degradation.

PMID- 29062129
TI  - I Am a Mystery to Myself.
AB  - Throughout my lifetime I have had a vague sense of my identity. There were no
      distinct memories or stories from my childhood and adolescence to provide me with
      the recognition, much less an appreciation, for who I was in the world. It wasn't
      until I entered psychotherapy that revelations about my family life came into
      understanding. This was not from any recollecting of actual events but from the
      indirect observations of families where being engaged with each other had
      occurred. Through psychoanalysis, reading a variety of psychoanalytic thinkers,
      and by taking up my own writing I was encouraged to discover myself, even at the
      cost of the sorrow of never having that encouragement in growing up, the cost
      that comes with the exploration. Where no childhood home was to be found a new
      one was to be created instead.

PMID- 29062130
TI  - Anti-semitism and Xenophobia.
AB  - This paper explores the link between anti-Semitism and xenophobia from a
      psychoanalytic prism. The author claims that anti-Semitism is a particular form
      of xenophobia directed against Jews, with some unique characteristics. She first
      introduces some basic notions about xenophobia, and then discusses the origins of
      anti-Semitism as they are viewed in early psychoanalytic thinking and in
      contemporary psychoanalysis. The article explores the nature of anti-Semitism in
      society today, and presents some reflections on the interplay between anti
      Semitism and other kinds of xenophobia.

PMID- 29062131
TI  - Pierre Janet and Auguste Forel: Two Historical Contributions.
AB  - This paper discusses two 19th century French-speaking authors, Pierre Janet and
      Auguste Forel, who both employed hypnosis and in various ways were early
      influences on psychoanalysis. To acquaint the reader with the clinical works of
      these pioneers, a long case history by Janet, and a case history by Forel are
      presented. The connections between these two authors and modern developments are
      discussed. Both historical figures were contemporaries of Freud and their at
      times contentious relationships became part of their legacy.

PMID- 29062132
TI  - Some Paths Towards Psychotic Alienation.
AB  - In this paper I use the term alienation to describe the mind's detachment from
      psychic reality and its withdrawal into an alien world that leads to progressive
      dehumanization. In spite of this phenomenon having a psychodynamic nosography and
      descriptive models that effectively reveal it in detail, mental alienation is
      still mysterious and unsettling, especially when it manifests all of a sudden in
      clinical work. Alienating withdrawal into sensory fantasizing, which causes
      increasing loss of contact with human reality, is often preceded by a long period
      of time spent in a dissociated world that has gradually replaced psychic reality.
      However, prior to the human world being completely replaced by the alien world,
      both worlds coexisted for a considerable length of time in the patient's mind. My
      hypothesis is that the dissociation from psychic reality that underlies the
      future state of psychotic alienation occurs in psychic withdrawal that begins in
      infancy. This mental state is particularly obvious in small children who
      constantly live in a fantasy world.

PMID- 29062133
TI  - Female alcohol consumption and fecundability: a systematic review and dose
      response meta-analysis.
AB  - To what extent could alcohol consumption affects female fertility is still
      unclear. The aim of this study was to quantitatively summarize the dose-response
      relation between total and specific types of alcohol beverage (beer, wine, and
      spirits) consumption in female and the fecundability. Four electronic databases
      were searched. Observational studies (cohort and case-control) that provided
      female alcohol consumption and fecundity were eligible. Nineteen studies,
      involving 98657 women, were included in this study. Compared to non-drinkers, the
      combined estimate (with relative risk, RR) of alcohol consumers on fecundability
      was 0.87 (95% CI 0.78-0.95) for overall 19 studies. Compared to non-drinkers, the
      pooled estimates were 0.89 (95% CI 0.82-0.97) for light drinkers (<=12.5 g/day of
      ethanol) and 0.77 (95% CI 0.61-0.94) for moderate-heavy drinkers (>12.5 g/day of
      ethanol). Moreover, compared to non-drinkers, the corresponding estimates on
      fecundability were 0.98 (95% CI 0.85-1.11), 1.02 (95% CI 0.99-1.05), and 0.92
      (95% CI 0.83-1.01) for studies focused on wine, beer and spirits, respectively.
      Dose-response meta-analysis suggested a linear association between decreased
      fecundability and every 12.5 g/d increasing in alcohol consumption with a RR 0.98
      (95% CI 0.97-0.99). This first systematic review and meta-analysis suggested that
      female alcohol consumption was associated with a reduced fecundability.

PMID- 29062134
TI  - Identification of a Different Agonist-Binding Site and Activation Mechanism of
      the Human P2Y1 Receptor.
AB  - The human P2Y1 receptor (P2Y1R) is a purinergic G-protein-coupled receptor (GPCR)
      that functions as a receptor for adenosine 5'-diphosphate (ADP). An antagonist of
      P2Y1R might potentially have antithrombotic effects, whereas agonists might serve
      as antidiabetic agents. On the basis of the antagonist-bound MRS2500-P2Y1R
      crystal structure, we constructed computational models of apo-P2Y1R and the
      agonist-receptor complex 2MeSADP-P2Y1R. We then performed conventional molecular
      dynamics (cMD) and accelerated molecular dynamics (aMD) simulations to study the
      conformational dynamics after binding with agonist/antagonist as well as the
      P2Y1R activation mechanism. We identified a new agonist-binding site of P2Y1R
      that is consistent with previous mutagenesis data. This new site is deeper than
      those of the agonist ADP in the recently simulated ADP-P2Y1R structure and the
      antagonist MRS2500 in the MRS2500-P2Y1R crystal structure. During P2Y1R
      activation, the cytoplasmic end of helix VI shifts outward 9.1 A, the Ser1463.47
      Tyr2375.58 hydrogen bond breaks, a Tyr2375.58-Val2626.37 hydrogen bond forms, and
      the conformation of the chi1 rotamer of Phe2696.44 changes from parallel to
      perpendicular to helix VI. The apo-P2Y1R system and the MRS2500-P2Y1R system
      remain inactive. The newly identified agonist binding site and activation
      mechanism revealed in this study may aid in the design of P2Y1R
      antagonists/agonists as antithrombotic/antidiabetic agents, respectively.

PMID- 29062135
TI  - Increased HSP27 correlates with malignant biological behavior of non-small cell
      lung cancer and predicts patient's survival.
AB  - Heat shock protein 27 (HSP27) has been found to be related to tumorigenesis. The
      aim of this study was to investigate the expression pattern and clinical
      significance of HSP27 in non-small-cell lung cancer (NSCLC). The expression of
      HSP27 in tissues was examined by immunohistochemistry and serum level of HSP27
      mRNA was detected by real-time PCR. The survival analysis was performed by a
      Kaplan Meier method and the estimation of risk factors was determined by the
      multiple regression analysis. The expression of HSP27 was increased in lung
      cancer tissues (p < 0.001) and serum (p < 0.001) of NSCLC patients and higher
      HSP27 in lung cancer tissues and serum of NSCLC patients was associated with
      poorly differentiated cancer (p < 0.001; p = 0.035), lymphatic metastasis (p <
      0.001; p < 0.001), advanced TNM stage (p < 0.001; p < 0.001). And the levels of
      HSP27 in tissues and serum of lung cancer patients had a certain positive
      correlation (p = 0.046). Moreover, increased HSP27 expression correlated with
      shorter survival of NSCLC patients (p < 0.001). The results suggest that HSP27
      may serve as a potential biomarker for diagnosis and prognosis of NSCLC.

PMID- 29062136
TI  - Resting site use of giant pandas in Wanglang Nature Reserve.
AB  - Little is known about the resting sites used by the giant panda (Ailuropoda
      melanoleuca), which restricts our understanding of their resting habits and
      limits conservation efforts. To enhance our understanding of resting site
      requirements and factors affecting the resting time of giant pandas, we
      investigated the characteristics of resting sites in the Wanglang Nature Reserve,
      Sichuan Province, China. The results indicated that the resting sites of giant
      pandas were characterised by a mean slope of 21 degrees , mean nearest tree size
      of 53.75 cm, mean nearest shrub size of 2.82 cm, and mean nearest bamboo number
      of 56. We found that the resting sites were closer to bamboo than to trees and
      shrubs, suggesting that the resting site use of giant pandas is closely related
      to the presence of bamboo. Considering that giant pandas typically rest near a
      large-sized tree, protection of large trees in the forests is of considerable
      importance for the conservation of this species. Furthermore, slope was found to
      be an important factor affecting the resting time of giant pandas, as they tended
      to rest for a relatively longer time in sites with a smaller degree of slope.

PMID- 29062137
TI  - Improved electrical and thermo-mechanical properties of a MWCNT/In-Sn-Bi
      composite solder reflowing on a flexible PET substrate.
AB  - Multi-walled carbon nanotube (MWCNT)/indium-tin-bismuth (In-Sn-Bi) composite
      nanostructures in which In-Sn-Bi nanoparticles have been penetrated by the MWCNT
      arrays were synthesized using a chemical reduction method. The incorporation of
      0.6 wt% MWCNTs with high electrical conductivity into the In-based solder
      resulted in low minimum electrical resistivity (19.9 +/- 1.0 uOmega.cm). Despite
      being reflowed at the relatively low temperature of 110  degrees C, the composite
      solder nanostructures were able to form mechanically stable solder bumps on a
      flexible polyethylene terephthalate (PET) substrate due to the MWCNT arrays with
      a high thermal conductivity of 3000 W/(m.K) and In-Sn-Bi nanoparticles with a low
      melting temperature of 98.2  degrees C. Notably, the composite solder bumps
      exhibited high flexibility (17.7% resistance increase over 1000 cycles of
      operation in a bending test) and strong adhesion strength (0.9 N average shear
      strength in a scratch test) on the plastic substrate because of the presence of
      mechanically flexible and strong MWCNTs dispersed within the solder matrix
      materials. These overall properties are due to the improved diffusivity of the
      composite solder nanostructures by the cover of the In-Sn-Bi nanoparticles along
      the MWCNT arrays and the network structure formation of the composite solder
      bumps.

PMID- 29062138
TI  - Increased complexity of mushroom body Kenyon cell subtypes in the brain is
      associated with behavioral evolution in hymenopteran insects.
AB  - In insect brains, the mushroom bodies (MBs) are a higher-order center for sensory
      integration and memory. Honeybee (Apis mellifera L.) MBs comprise four Kenyon
      cell (KC) subtypes: class I large-, middle-, and small-type, and class II KCs,
      which are distinguished by the size and location of somata, and gene expression
      profiles. Although these subtypes have only been reported in the honeybee, the
      time of their acquisition during evolution remains unknown. Here we performed in
      situ hybridization of tachykinin-related peptide, which is differentially
      expressed among KC subtypes in the honeybee MBs, in four hymenopteran species to
      analyze whether the complexity of KC subtypes is associated with their behavioral
      traits. Three class I KC subtypes were detected in the MBs of the eusocial hornet
      Vespa mandarinia and the nidificating scoliid wasp Campsomeris prismatica, like
      in A. mellifera, whereas only two class I KC subtypes were detected in the
      parasitic wasp Ascogaster reticulata. In contrast, we were unable to detect class
      I KC subtype in the primitive and phytophagous sawfly Arge similis. Our findings
      suggest that the number of class I KC subtypes increased at least twice - first
      with the evolution of the parasitic lifestyle and then with the evolution of
      nidification.

PMID- 29062139
TI  - DDX3 regulates endoplasmic reticulum stress-induced ATF4 expression.
AB  - Accumulation of unfolded and potentially toxic proteins in the endoplasmic
      reticulum (ER) activates a cell stress adaptive response, which involves a
      reprogramming of general gene expression. ATF4 is a master stress-induced
      transcription factor that orchestrates gene expression in cells treated with
      various ER stress inducers including those used to treat cancers. ER stress
      induced ATF4 expression occurs mainly at the translational level involving the
      activity of the phosphorylated (P) translation initiation factor (eIF) eIF2alpha.
      While it is well established that under ER stress PeIF2alpha drives ATF4
      expression through a specialised mode of translation re-initiation, factors (e.g.
      RNA-binding proteins and specific eIFs) involved in PeIF2alpha-mediated ATF4
      translation remain unknown. Here we identified the RNA-binding protein named DDX3
      as a promotor of ATF4 expression in cancer cells treated with sorafenib, an ER
      stress inducer used as a chemotherapeutic. Depletion experiments showed that DDX3
      is required for PeIF2alpha-mediated ATF4 expression. Luciferase and polyribosomes
      assays showed that DDX3 drives ER stress-induced ATF4 mRNA expression at the
      translational level. Protein-interaction assays showed that DDX3 binds the eIF4F
      complex, which we found to be required for ER stress-induced ATF4 expression.
      This study thus showed that PeIF2alpha-mediated ATF4 mRNA translation requires
      DDX3 as a part of the eIF4F complex.

PMID- 29062140
TI  - Enhanced Cell Adhesion on a Nano-Embossed, Sticky Surface Prepared by the
      Printing of a DOPA-Bolaamphiphile Assembly Ink.
AB  - Inspired by adhesive mussel proteins, nanospherical self-assemblies were prepared
      from bolaamphiphiles containing 3,4-dihydroxyphenylalanine (DOPA) moieties, and a
      suspension of the bolaamphiphile assemblies was used for the preparation of a
      patterned surface that enhanced cell adhesion and viability. The abundant surface
      exposed catechol groups on the robust bolaamphiphile self-assemblies were
      responsible for their outstanding adhesivity to various surfaces and showed
      purely elastic mechanical behaviour in response to tensile stress. Compared to
      other polydopamine coatings, the spherical DOPA-bolaamphiphile assemblies were
      coated uniformly and densely on the surface, yielding a nano-embossed surface.
      Cell culture tests on the surface modified by DOPA-bolaamphiphiles also showed
      enhanced cellular adhesivity and increased viability compared to surfaces
      decorated with other catecholic compounds. Furthermore, the guided growth of a
      cell line was demonstrated on the patterned surface, which was prepared by inkjet
      printing using a suspension of the self-assembled particles as an ink. The self
      assembly of DOPA-bolaamphiphiles shows that they are a promising adhesive,
      biocompatible material with the potential to modify various substances.

PMID- 29062141
TI  - Immunometabolism: Oxygen sensing and cell metabolism in inflammation.

PMID- 29062143
TI  - Probing the Limits of Supramolecular G-Quadruplexes Using Atomistic Molecular
      Dynamics Simulations.
AB  - Guanosine and related derivatives self-assemble in the presence of cations like
      potassium into supramolecular G-quadruplexes (SGQs), where four guanine moieties
      form planar tetrads (T) that coaxially stack into columnar aggregates with broad
      size distributions. However, SGQs made from 8-aryl-2'-deoxyguanosine derivatives
      (8ArGs), form mostly octamers, or two-tetrad (2T)-SGQs, while some form
      dodecamers (3T-SGQs), or hexadecamers (4T-SGQs), and none reported to date form
      higher assemblies. A theoretical model that addresses the configurational space
      available for the multiple pathways available for 8ArGs to self-assemble into
      SGQs is used to frame a series of molecular dynamics simulations (MDS) with
      selected SGQs. Some key insights from this work include: (a) The predicted
      entropic costs are not significantly higher for SGQs with more subunits due to
      their hierarchical assembly pathways; (b) The multiple isomeric SGQs vary in the
      interfacial contacts between consecutive tetrads, due to their two distinct sides
      (head, h; tail, t), with the MDS supporting the predicted order of stability of
      hh > ht > tt for octamers. (c) Such order also applies to dodecamers and
      hexadecamers, but with context-dependent exceptions due to strong allosteric
      effects. (d) The main factor disfavoring the tt interface is the repulsive
      dipolar interactions between the O4' from ribose moieties on adjacent tetrads.
      (e) SGQs with 5 or more tetrads are disfavored because the attractive
      interactions are not large or strong enough to overcome the many repulsive forces
      resulting from the addition of further tetrads. We expect these findings provide
      some guidelines to enable the further development of SGQs into functional
      materials.

PMID- 29062142
TI  - Modelling diabetic nephropathy in mice.
AB  - Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the
      developed world. Accordingly, an urgent need exists for new, curative treatments
      as well as for biomarkers to stratify risk of DN among individuals with diabetes
      mellitus. A barrier to progress in these areas has been a lack of animal models
      that faithfully replicate the main features of human DN. Such models could be
      used to define the pathogenesis, identify drug targets and test new therapies.
      Owing to their tractability for genetic manipulation, mice are widely used to
      model human diseases, including DN. Questions have been raised, however, about
      the general utility of mouse models in human drug discovery. Standard mouse
      models of diabetes typically manifest only modest kidney abnormalities, whereas
      accelerated models, induced by superimposing genetic stressors, recapitulate key
      features of human DN. Incorporation of systems biology approaches and emerging
      data from genomics and metabolomics studies should enable further model
      refinement. Here, we discuss the current status of mouse models for DN, their
      limitations and opportunities for improvement. We emphasize that future efforts
      should focus on generating robust models that reproduce the major clinical and
      molecular phenotypes of human DN.

PMID- 29062144
TI  - Fraction-exponential representation of the viscoelastic properties of dentin.
AB  - We propose the fraction-exponential description of the viscoelastic properties of
      dentin. Creep tests are performed on specimens cut from the molar coronal part.
      Four parameters determining instantaneous and long term Young's moduli as well as
      the relaxation time are extracted from the experimental data. The same procedure
      is repeated using the experimental measurements of Jantarat et al (2002) for the
      specimens cut from the root part of incisor. Physical meaning of the parameters
      and the difference between them for different sets of specimens are discussed.

PMID- 29062145
TI  - Morphological and Molecular Identification of Longidorus euonymus and
      Helicotylenchus multicinctus from the Rhizosphere of Grapevine and Banana in
      Greece.
AB  - Plant-parasitic nematodes such as Longidorus euonymus and Helicotylenchus
      multicintctus are species widely distributed in central Europe as well as in
      Mediterranean area. In Greece, both species have been previously reported but no
      morphometrics or molecular data were available for these species. Nematode
      surveys in the rhizosphere of grapevines in Athens carried out in 2016 and 2017,
      yielded a Longidorus species identified as Longidorus euonymus. Similarly, a
      population of Helicotylenchus multicinctus was detected infecting banana roots
      from an outdoor crop in Tertsa, Crete. For both species, morphometrics and
      molecular data of Greek populations were provided, resulting in the first
      integrative identification of both nematode species based on morphometric and
      molecular markers, confirming the occurrence of these two nematodes in Greece as
      had been stated in earlier reports.

PMID- 29062146
TI  - An 18S rDNA Perspective on the Classification of Criconematoidea.
AB  - In the nematode family Criconematidae, a taxonomy primarily based on cuticle
      characters has created classifications that are notoriously volatile. Molecular
      characters may lead to their stabilization. A phylogenetic tree of
      Criconematoidea was constructed using 166 new near full-length 18S rDNA sequences
      and 58 sequences from GenBank. Bayesian and maximum likelihood (ML) analyses
      produced trees with similar topologies. Major features include a strongly
      supported clade that includes Criconematidae and Hemicycliophoridae, excluding
      Paratylenchidae and Tylenchulidae. Another well-supported clade groups Criconema,
      Ogma, Crossonema, and Hemicriconemoides plus Xenocriconemella, combining
      nematodes with cuticular scales with those without scales at any life stage.
      Mesocriconema, Discocriconemella limitanea, Hemicaloosia, and Lobocriconema are
      recognized as monophyletic groups, but Criconemoides is paraphyletic. Both trees
      support an unexpected sister relationship between Bakernema and Hemicycliophora.
      The 18S rDNA dataset was insufficient for distinguishing genus boundaries between
      Criconema, Ogma, and Crossonema. The relationships depicted by the 18S rDNA
      phylogeny suggest that key morphological characters used in the classification of
      Criconematidae are not homologous.

PMID- 29062147
TI  - Taxonomy and Systematics of the Genus Makatinus Heyns, 1965 (Nematoda:
      Dorylaimida: Aporcelaimidae).
AB  - The taxonomy and the systematics of the genus Makatinus are discussed by means of
      the characterization of its morphological pattern and the first molecular (D2-D3
      expansion segments of 28S rDNA) analysis of a representative of this taxon,
      Makatinus crassiformis from Costa Rica. The presence of two or more pairs of male
      ad-cloacal genital papillae is the most characteristic autapomorphy of the genus,
      but the status of its species on this concern differ among them. Both
      morphological and molecular data support a relationship with Aporcelaimellus,
      which, however, might not be as close as usually assumed. An emended diagnosis of
      the genus, a key to species identification, and a compendium of their
      morphometrics are provided. Makatinus siddiqii is regarded as species inquirenda,
      Makatinus simus is retained under Eudorylaimus, and Makatinus tritici becomes a
      junior synonym of Aporcelaimellus tritici.

PMID- 29062148
TI  - Morphological, Morphometric, and Molecular Characterization of Intraspecific
      Variations within Indian Populations of Meloidogyne graminicola.
AB  - Fourteen populations of Meloidogyne graminicola were collected from different
      agroecological regions of India. Morphological and morphometrical comparisons
      were made for various nematode life stages. Three populations (Hisar, New Delhi,
      and Samastipur) were different from typical M. graminicola on the basis of the
      length of eggs; J2 length, a-value, hyaline tail portion; male length, distance
      up to excretory pore, spicule and gubernaculum lengths; female length and width,
      stylet length, distance up to excretory pore, EPST (distance of excretory pore
      from anterior end / stylet length [females]) ratio, and vulval length.
      Morphological and morphometrical comparison with closely related species M.
      graminis, M. oryzae, M. salasi, M. triticoryzae, and M. lini clustered these
      populations into two groups: Anand, Bhubaneswar, Hyderabad, Jammu, Jorhat,
      Kalyani, Kanpur, Ludhiana, Mandya, Palampur, Vellayani grouped with M.
      graminicola, M. triticoryzae and M. salasi; whereas, Hisar, New Delhi, Samastipur
      grouped with M. oryzae and M. graminis. Molecular phylogenetic analysis using
      internal transcribed spacer (ITS) suggested that in spite of morphological
      differences, these populations belonged to M. graminicola.

PMID- 29062149
TI  - Description of a New Anguinid Nematode, Nothotylenchus phoenixae n. sp.
      (Nematoda: Anguinidae) Associated with Palm Date Trees and Its Phylogenetic
      Relations within the Family Anguinidae.
AB  - Nothotylenchus phoenixae n. sp. is described and illustrated from soil samples of
      palm trees in Kermanshah Province, western Iran. The new species is characterized
      by a body length of 784 (663 to 925) MUm in females and 677 to 715 MUm in males;
      a delicate stylet 6 (5 to 7) MUm long and six lines in the lateral field; median
      bulb of pharynx fusiform, nonmuscular, and nonvalvate; isthmus elongate, slender
      ending to a pyriform basal pharyngeal bulb not overlapping intestine; postvulval
      uterine sac well developed, 15 (14 to 17) MUm long, female tail elongate-conoid
      with pointed terminus; and male with adanal bursa and spicules 21 to 22 MUm long
      (n = 2). The new species comes close in morphology and morphometrics to five
      known species of the genus, namely N. affinis, N. hexaglyphus, N. persicus, N.
      taylori, and N. uniformis. Molecular analyses of the partial 18S, D2/D3 expansion
      segments of the partial 28S and internal transcribed spacer (ITS) revealed this
      as a new species. The sequences of the partial 18S and 28S D2/D3 regions
      confirmed the close phylogenetic relationship between N. phoenixae n. sp. and
      other anguinids, but Nothotylenchus is clearly separated from Ditylenchus species
      and should be considered as a valid genus.

PMID- 29062150
TI  - Morphological and Molecular Characteristics of Pratylenchus haiduongensis sp. n.,
      a New Species of Root-Lesion Nematodes Associated with Carrot in Vietnam.
AB  - Pratylenchus haiduongensis sp. n. is described as associated with carrot (Daucus
      carota subsp. sativus (Hoffm.) Schubl. & G. Martens) in Hai Duong Province,
      Vietnam. P. haiduongensis sp. n. is characterized by the lip region with three
      annuli and slightly separated from the body. Stylet knobs are rounded (never
      indented anteriorly). The lateral field includes four incisures, bearing
      areolation at the pharynx region and tail region and occasionally appears in the
      vulval region. Sometimes the appearances of oblique broken striaes divide the
      lateral field into five or six incisures. The ovary is distinct with one row of
      oocytes. Spermatheca is oval in shape with round central cavity, without sperm or
      reduced in some specimens. The postvuval uterine sac is long surpassing the vulva
      body diameter by 2 to 2.5 times (PUS = 31 to 65 um). High vulva position with V =
      66 to 75%. The tail shape can be subhemispherical with a smooth, slightly
      indented, broadly smooth, or cleft terminus observed in some specimens. The
      matrix code of P. haiduongensis sp. n. is: A2, B1, C4, D(1,3), E1, F(5,6),
      G(1,2), H(1,4); I(1,2,3,4), J1, K(1,2) according to Castillo and Vovlas (2007).
      The LSU-D2D3 segment and the ITS-rDNA region of this species were amplified and
      sequenced. The morphological characters and molecular phylogenetic analyses
      confirmed that this is a new species of the genus Pratylenchus in Vietnam.

PMID- 29062151
TI  - A New Species of the Rare Genus Anguillonema Fuchs, 1938 (Nematoda: Hexatylina,
      Sphaerularioidea) with Its Molecular Phylogenetic Study.
AB  - Anguillonema amolensis n. sp. is described and illustrated based on its
      morphological, morphometric, and molecular characters. The new species is
      characterized by its 575 to 820 MUm long and wide body (body width at vulva = 30
      to 59 MUm), irregularly ventrally curved after fixation, five to six lines in
      lateral fields, 6.0 to 7.5 MUm long stylet with small rounded knobs, pharynx
      lacking a median bulb, pharyngo-intestinal junction anterior to nerve ring and
      excretory pore, females with monodelphic-prodelphic reproductive system, 15 to 19
      MUm long conical tail with broad rounded tip, and males absent. The new species
      is compared with two known species of the genus, Anguillonema poligraphi and A.
      crenati. Molecular phylogenetic studies of the new species using partial
      sequences of small subunit (SSU) rDNA revealed that it forms a clade with an
      unidentified nematode species and two species of the genus Howardula. In
      phylogenetic analyses using partial sequences of the 28S rDNA (D2-D3 segment),
      the new species formed a monophyletic group with species belonging to two genera
      Howardula and Parasitylenchus.

PMID- 29062152
TI  - Nematicidal Effects of 5-Aminolevulinic Acid on Plant-Parasitic Nematodes.
AB  - Plant-parasitic nematodes are important agricultural pests and often cause
      serious crop losses. Novel, environmental friendly nematicides are urgently
      needed because of the harmful effects of some existing nematicides on human
      health. 5-Aminolevulinic acid (ALA) was reported as a potential biodegradable
      herbicide, insecticide, or plant-growth promoting agent. Lack of information on
      ALA against plant-parasitic nematodes prompted this investigation to determine
      the effects of ALA on Meloidogyne incognita, Heterodera glycines, Pratylenchus
      coffeae, and Bursaphelenchus xylophilus. A series of in vitro assays and one
      greenhouse trial were conducted to examine the nematicidal effects of ALA. The
      results demonstrated that ALA exhibited a strong effect of suppression against
      the four nematodes tested. ALA also inhibited hatching of M. incognita and H.
      glycines. Results from the greenhouse experiment indicated that treatment of soil
      with 6.0 mM ALA significantly reduced the root-gall index (RGI) and egg mass
      number per root system compared with the uninoculated control (P <= 0.05). The
      metabolism assays indicated that ALA treatment significantly altered the nematode
      metabolism including the total protein production, malondialdehyde (MDA) content,
      and oxidase activities. This study suggested that ALA is a promising nematicide
      against plant-parasitic nematodes.

PMID- 29062153
TI  - Influence of Root Exudates and Soil on Attachment of Pasteuria penetrans to
      Meloidogyne arenaria.
AB  - The bacterium Pasteuria penetrans is a parasite of root-knot nematodes
      (Meloidogyne spp.). Endospores of P. penetrans attach to the cuticle of second
      stage juveniles (J2) and subsequently sterilize infected females. When encumbered
      by large numbers of spores, juveniles are less mobile and their ability to infect
      roots is reduced. This study looked at different factors that influence spore
      attachment of P. penetrans to the root-knot nematode Meloidogyne arenaria.
      Pretreatment of J2 with root exudates of eggplant (Solanum melongena cv. Black
      beauty) reduced spore attachment compared with pretreatment with phosphate
      buffered saline (PBS), suggesting that the nematode surface coat was altered or
      the spore recognition domains on the nematode surface were blocked. Spore
      attachment was equally reduced following exposure to root exudates from both host
      and nonhost plants for M. arenaria, indicating a common signal that affects spore
      attachment. Although phytohormones have been shown to influence the lipophilicity
      of the nematode surface coat, auxins and kinetins did not affect spore attachment
      compared with PBS. Root exudates reduced spore attachment more in sterilized soil
      than in natural soil. Sterilization may have eliminated microbes that consume
      root exudates, or altered the chemical components of the soil solution or root
      exudates. Root exudates caused a greater decrease in spore attachment in loamy
      sand than in a sandy loam soil. The sandy loam had higher clay content than the
      loamy sand, which may have resulted in more adsorption of compounds in the root
      exudates that affect spore attachment. The components of the root exudates could
      have also been modified by soil type. The results of this study demonstrate that
      root exudates can decrease the attachment of P. penetrans endospores to root-knot
      nematodes, indicating that when these nematodes enter the root zone their
      susceptibility to spore attachment may decrease.

PMID- 29062154
TI  - Vertical Distribution of Pasteuria penetrans Parasitizing Meloidogyne incognita
      on Pittosporum tobira in Florida.
AB  - Pasteuria penetrans is considered as the primary agent responsible for soil
      suppressiveness to root-knot nematodes widely distributed in many agricultural
      fields. A preliminary survey on a Pittosporum tobira field where the grower had
      experienced a continuous decline in productivity caused by Meloidogyne incognita
      showed that the nematode was infected with Pasteuria penetrans. For effective
      control of the nematode, the bacterium and the host must coexist in the same root
      zone. The vertical distribution of Pasteuria penetrans and its relationship with
      the nematode host in the soil was investigated to identify (i) the vertical
      distribution of P. penetrans endospores in an irrigated P. tobira field and (ii)
      the relationship among P. penetrans endospore density, M. incognita J2 population
      density, and host plant root distribution over time. Soil bioassays revealed that
      endospore density was greater in the upper 18 cm of the top soil compared with
      the underlying depths. A correlation analysis showed that the endospore density
      was positively related to the J2 population density and host plant root
      distribution. Thus, the vertical distribution of P. penetrans was largely
      dependent on its nematode host which in turn was determined by the distribution
      of the host plant roots. The Pasteuria was predominant mostly in the upper layers
      of the soil where their nematode host and the plant host roots are abundant, a
      factor which may be a critical consideration when using P. penetrans as a
      nematode biological control agent.

PMID- 29062155
TI  - Superparasitism and Population Regulation of the Mosquito-Parasitic Mermithid
      Nematodes Romanomermis iyengari and Strelkovimermis spiculatus.
AB  - Superparasitism is a common phenomenon in mosquito-parasitic mermithid nematodes.
      Multiple nematodes are needed in a single host to produce males. Host selection
      behavior and intraspecific competition among Romanomermis iyengari and
      Strelkovimermis spiculatus were investigated against their host, Culex pipiens
      pipiens in laboratory experiments. In a choice assay between previously infected
      and uninfected host larvae, infectious preparasites of both nematode species
      could distinguish not only between infected and uninfected hosts, but even
      between different parasite loads in showing a strong preference for uninfected
      hosts or hosts with a low parasite load. Host heart rate declined briefly
      immediately after parasitism. Superparasitism resulted in increased parasite
      mortality. Scramble competition within mosquito larvae for limited host
      nutrients, coupled with a skewed sex ratio favoring males, is assumed to lead to
      parasite population decline and subsequently toward host-parasite population
      equilibrium. The ability of mermithid preparasites to accurately assess parasite
      load likely plays an important role in host population dynamics and regulation.

PMID- 29062156
TI  - A New Race (X12) of Soybean Cyst Nematode in China.
AB  - The soybean cyst nematode (SCN), Heterodera glycines, is a serious economic
      threat to soybean-producing regions worldwide. A new SCN population (called race
      X12) was detected in Shanxi province, China. Race X12 could reproduce on all the
      indicator lines of both race and Heterodera glycines (HG) type tests. The average
      number of females on Lee68 (susceptible control) was 171.40 with the lowest
      Female Index (FI) 61.31 on PI88788 and the highest FI 117.32 on Pickett in the
      race test. The average number of females on Lee68 was 323.17 with the lowest FI
      44.18 on PI88788 and the highest FI 97.83 on PI548316 in the HG type test.
      ZDD2315 and ZDD24656 are elite resistant germplasms in China. ZDD2315 is highly
      resistant to race 4, the strongest infection race in the 16 races with FI 1.51
      while being highly sensitive to race X12 with FI 64.32. ZDD24656, a variety
      derived from PI437654 and ZDD2315, is highly resistant to race 1 and race 2.
      ZDD24656 is highly sensitive to race X12 with FI 99.12. Morphological and
      molecular studies of J2 and cysts confirmed the population as the SCN H.
      glycines. This is a new SCN race with stronger virulence than that of race 4 and
      is a potential threat to soybean production in China.

PMID- 29062157
TI  - The Mesostigmatid Mite Protogamasellus mica, an Effective Predator of Free-Living
      and Plant-Parasitic Nematodes.
AB  - Protogamasellus mica was extracted from a sugarcane field in Australia and
      cultured on bacterial-feeding nematodes. Studies with various nematodes in
      laboratory arenas showed that one mite and its progeny reduced nematode numbers
      by between 26 and 50 nematodes/day. A bacterivore (Mesorhabditis sp.), a
      fungivore (Aphelenchus avenae), and two plant parasites (root-knot nematode,
      Meloidogyne javanica and root-lesion nematode, Pratylenchus zeae) were all
      reduced at much the same rate despite the fact that the nematodes are quite
      different in size and motility and belong to different trophic groups. When
      sugarcane was grown in the greenhouse for 8 wk, stunt nematode (Tylenchorhynchus
      annulatus), a plant parasite that feeds ectoparasitically on roots, was almost
      eliminated from pots inoculated with the mite, and numbers of microbivores and
      root-lesion nematode were markedly reduced. Huge reductions in nematode
      populations were also observed when mites were added to microcosms containing
      small quantities of defaunated soil. These results show that P. mica multiplies
      rapidly when nematodes are available as a food source and has the capacity to
      play a role in regulating populations of both plant-parasitic and free-living
      nematodes. Future research should focus on understanding the crop and soil
      management practices required to enable this mite and other predatory species to
      thrive.

PMID- 29062158
TI  - Expression of CeHSP17 Protein in Response to Heat Shock and Heavy Metal Ions.
AB  - Small heat shock proteins (sHSP) are ubiquitously found in all organisms, and
      with other heat shock proteins (HSP) such as HSP60, HSP70, HSP90, HSP100 made up
      the molecular chaperone family. They are involved in a wide range of biological
      processes which include among others cell resistance to biological and
      environmental stress conditions. In this study, we show by western blotting that
      CeHSP17, an sHSP of Caenorhabiditis elegans, is significantly induced by high
      temperatures. Furthermore, in response to metal stress, the CeHSP17 protein
      expression was significantly induced by cadmium and zinc at high concentration of
      clearly cytotoxic range in wild-type C. elegans. Altogether, our results show the
      involvement of CeHSP17 protein in both environmental and biological stresses in
      C. elegans and establish for the first time the expression pattern of the CeHSP17
      protein in response to thermal and metal stress conditions in C. elegans. The
      responses of CeHSP17 protein expression may serve as potential sensitive
      biomarker for metal-induced toxicity monitoring and environmental risk
      assessment.

PMID- 29062159
TI  - Brain Atlas Fusion from High-Thickness Diagnostic Magnetic Resonance Images by
      Learning-Based Super-Resolution.
AB  - It is fundamentally important to fuse the brain atlas from magnetic resonance
      (MR) images for many imaging-based studies. Most existing works focus on fusing
      the atlases from high-quality MR images. However, for low-quality diagnostic
      images (i.e., with high inter-slice thickness), the problem of atlas fusion has
      not been addressed yet. In this paper, we intend to fuse the brain atlas from the
      high-thickness diagnostic MR images that are prevalent for clinical routines. The
      main idea of our works is to extend the conventional groupwise registration by
      incorporating a novel super-resolution strategy. The contribution of the proposed
      super-resolution framework is two-fold. First, each high-thickness subject image
      is reconstructed to be isotropic by the patch-based sparsity learning. Then, the
      reconstructed isotropic image is enhanced for better quality through the random
      forest-based regression model. In this way, the images obtained by the super
      resolution strategy can be fused together by applying the groupwise registration
      method to construct the required atlas. Our experiments have shown that the
      proposed framework can effectively solve the problem of atlas fusion from the low
      quality brain MR images.

PMID- 29062160
TI  - Single Electrospun PLLA and PCL Polymer Nanofibers: Increased Molecular
      Orientation with Decreased Fiber Diameter.
AB  - Electrospinning has become a widely-used method for fabricating polymer
      nanofibers for various applications including filtration, drug delivery, and
      tissue engineering. Due to the high extensional forces during the electrospinning
      process, and the rapid crystallization and solidification during solvent
      evaporation, molecular orientation may develop within the resulting fibers. The
      properties of electrospun fibers are expected to be sensitive to level of
      orientation in the fibers. Various reports have shown an increased modulus with
      decreased fiber diameter, and molecular orientation has been used to explain this
      trend. However, there have been relatively few studies of the detailed
      relationship between fiber diameter and molecular orientation, especially at the
      single fiber level. Here we report a quantitative study of the orientation in
      individual electrospun poly(caprolactone) (PCL) and poly(L-lactic acid) (PLLA)
      fibers using low-dose electron microscopy and diffraction techniques. Our results
      confirmed that for electrospun fibers of PCL and PLLA processed under similar
      experimental conditions, the molecular orientation decreased as the fiber
      diameter increased. The extent of orientation remained high for quite large fiber
      diameters, with azimuthal orientation of 20 degrees seen up to ~500 nm for PCL
      and ~2000 nm for PLLA.

PMID- 29062161
TI  - The Relationship Between the Normalized Gradient Addition Mechanism and Quadratic
      Voting.
AB  - Quadratic Voting and the Normalized Gradient Addition mechanism are both social
      choice mechanisms that confront individuals with quadratic budget constraints,
      but they are applicable in different contexts. Adapting one or both to apply to
      the same context, this paper explores the relationship between these two
      mechanisms in three contexts: marginal adjustments of continuous policies,
      simultaneous voting on many public choices, and voting on a single public choice
      accompanied by private monetary consequences. In the process, we provide some
      formal analysis of Quadratic Voting when (instead of money) votes are paid for
      with abstract tokens that are equally distributed by the mechanism designer.

PMID- 29062162
TI  - Low temperatures during ontogeny increase fluctuating asymmetry and reduce
      maternal aggression in the house mouse, Mus musculus.
AB  - Maternal aggression is behavior displayed by post-partum lactating female mice
      toward unfamiliar conspecifics, presumably as a defense against infanticide. A
      variety of perinatal stressors can impair maternal care in adulthood. Previous
      studies on associations between developmental perturbations and maternal
      aggression have produced mixed results. To address this issue, we employed a
      proxy for developmental instability, fluctuating asymmetry (FA) to further
      elucidate the relationship between low temperature stress and maternal
      aggression. FA, small, random deviations from perfect symmetry in bilateral
      characters is used as a quantitative measure of stress during ontogeny. Dams were
      either maintained in standard laboratory temperatures (21 +/- 2  degrees C), or
      cold temperatures (8 +/- 2  degrees C) during gestation. During lactation, their
      progeny either remained in the temperature condition in which they were gestated
      or were transferred to the other temperature condition. Four individual measures
      of FA, a composite of these measures, and three measures of maternal aggression
      were assessed in the female progeny in adulthood. Exposure to low temperatures
      during both pre- and early post-natal development increased composite FA and
      reduced all three measures of maternal aggression compared to controls. Exposure
      to low temperatures during the pre- or postnatal period alone did not induce
      either high FA or altered maternal aggression. Certain measures of FA and nest
      defense were negatively correlated. Our results suggest that low temperatures
      experienced during gestation and lactation may have important fitness costs. Low
      maternal aggression towards infanticidal conspecifics is likely to limit the
      number of offspring surviving into adulthood. Overall, FA appears to be a
      reliable indicator of chronic developmental stress with implications for fitness.

PMID- 29062164
TI  - Bioconjugated graphene oxide-based Raman probe for selective identification of
      SKBR3 breast cancer cells.
AB  - In this article, we demonstrate the use of bio-conjugated 2D graphene oxide (bio
      GO) nanostructure to probe breast cancer cell (SKBR3) with excellent
      discrimination over other types of circulating tumor cells. We distinctly
      observed that bio-GO nanostructure targets and bind SKBR3 cell selectively in the
      cell mixture. Longer incubation of SKBR3 cell with bio-GO causes Raman signal
      "turn off" when excited with 532 nm laser. This is attributed to penetration of
      the bio-GO through the plasma membrane of the cell by generating transient hole.
      Extraction of GO after cell digestion also support the internalization rubric of
      2D graphene through cell membrane. Our experimental data with the HaCaT healthy
      cell line, as well as with LNCaP prostate cancer cell line clearly demonstrated
      that this Raman scattering assay is highly selective to SKBR3. The mechanism of
      selectivity and the assay's response change have been verified and discussed
      utilizing fluorescence properties of GO and various other techniques. The
      experimental results open up a possibility of new label free Raman scattering
      assay, for reliable diagnosis of cancer cell lines by monitoring "turn-off" of
      the Raman signal from Bio-GO nanostructure.

PMID- 29062163
TI  - The Prognostic Value of Decreased KLF4 in Digestive System Cancers: A Meta
      Analysis from 17 Studies.
AB  - BACKGROUND: The prognostic value of loss of Kruppel-like factor 4 (KLF4)
      expression in digestive system cancers has not reached a consensus. This study
      aimed for a comprehensive investigation of the internal associations between KLF4
      expression loss and prognostic implications in patients with digestive system
      cancers. METHODS: We searched for all relevant literatures in the electronic
      databases until February 1, 2017. The degree of association between KLF4 and
      prognosis was evaluated by pooled hazard ratios (HRs) as well as relevant 95%
      confidence intervals (95% CIs). RESULTS: Seventeen eligible studies with 2118
      patients revealed that loss of KLF4 expression was connected with poor prognosis,
      with the pooled HRs of 1.61 (95% CI: 1.17-2.20, P = 0.003) for the overall
      survival (OS) and 1.99 (95% CI: 1.12-3.52, P = 0.001) for the disease-free
      survival (DFS)/recurrence-free survival (RFS)/metastasis-free survival (MFS).
      Additionally, loss of KLF4 expression was also related to a worse disease-special
      survival (DSS) yielding a pooled HR of 1.73 (95% CI: 1.08-2.77, P = 0.022).
      CONCLUSION: Our findings suggest that loss of KLF4 expression is correlated with
      a bad outcome in most digestive system cancers, apart from esophagus squamous
      cell carcinoma (ESCC).

PMID- 29062165
TI  - At the intersection of criminal justice involvement and sexual orientation:
      Dynamic networks and health among a population-based sample of young Black men
      who have sex with men.
AB  - Mass incarceration of young Black men has a significant impact on their network
      composition and stability that, in turn, may have major implications for health
      and well-being. A sub-group of young Black men with criminal justice involvement
      (CJI) identify as gay, bisexual or are non-identified men who have sex with men
      (hereafter MSM). This paper focuses on the potential effects of CJI on the
      composition of Black MSM social and sexual networks, their stability over time,
      and concomitant health and social outcomes. We use data from the UConnect study,
      a population-based cohort of young Black MSM 16-29 years of age (n=618) selected
      using respondent-driven sampling in Chicago from 2013-2016. Both confidant and
      sexual network name generators and interpreters were administered at 9-month
      intervals over three waves of data collection. Ego and dyadic-level data were
      collected on behaviors prevalent among MSM and including factors associated with
      network CJI, network stability, and health outcomes. Generalized Structural
      Equation Models (GSEM) were utilized to determine the relationship between CJI
      network composition, network stability and behaviors prevalent among young Black
      MSM and their networks. In the UConnect cohort, 46% had at least once been
      detained, arrested or spent time in jail or prison. In addition, 20% of
      participants reported incident CJI over the study period. Respondents with a
      history of CJI were significantly more likely to have CJI homophily in their
      confidant and sexual networks. Multivariate analyses demonstrate that the
      association between one's history of CJI, housing instability and drug use is
      partially explained by one's network CJI. In addition, a higher prevalence of
      network CJI is associated with increased turnover in the confidant network, and
      this network instability is also related to important health and social outcomes.
      This analysis describes the networks of criminal justice involved men among a
      representative sample of young Black MSM and demonstrates the relationship
      between CJI network homophily, network stability and their impact on several key
      health and social outcomes relevant to this population.

PMID- 29062166
TI  - Growth factor functionalized biomaterial for drug delivery and tissue
      regeneration.
AB  - Elastin like polypeptides (ELPs) are a class of naturally derived and non
      immunogenic biomaterials that are widely used in drug delivery and tissue
      engineering. ELPs undergo temperature-mediated inverse phase transitioning, which
      allows them to be purified in a relatively simple manner from bacterial
      expression hosts. Being able to genetically encode ELPs allows for the
      incorporation of bioactive peptides thereby functionalizing them. Here we report
      the synthesis of a biologically active epidermal growth factor-ELP (EGF-ELP)
      fusion protein that could aid in wound healing. EGF plays a crucial role in wound
      healing by inducing cell proliferation and migration. The use of exogenous EGF
      has seen success in the treatment of acute wounds, but has seen relatively
      minimal success in chronic wounds because the method of delivery does not prevent
      it from diffusing away from the application site. Our data shows that EGF-ELP
      retained the biological activity of EGF and the phase transitioning property of
      ELP. Furthermore, the ability of the EGF-ELP to self-assemble near physiological
      temperatures could allow for the formation of drug depots at the wound site and
      minimize diffusion, increasing the bioavailability of EGF and enhancing tissue
      regeneration.

PMID- 29062167
TI  - Characterization of the Foreign Body Response to Common Surgical Biomaterials in
      a Murine Model.
AB  - BACKGROUND: Implanted biomaterials are subject to a significant reaction from the
      host, known as the foreign body response (FBR). We quantified the FBR to five
      materials following subcutaneous implantation in mice. MATERIALS AND METHODS:
      Polyvinyl alcohol (PVA) and silicone sheets are considered highly biocompatible
      biomaterials and were cut into 8mm-diameter disks. Expanded PTFE (ePTFE)and
      polypropylene are also widely used biocompatible biomaterials and were cut into
      2cm-long cylinders. Cotton was selected as a negative control material that would
      invoke an intense FBR, was cut into disks and implanted. The implants were
      inserted subcutaneously into female C57BL/6 mice. On post-implantation days 14,
      30, 60, 90 and 180, implants were retrieved. Cellularity was assessed with DAPI
      stain, collagen with Masson's trichrome stain. mast cells with toluidine-blue,
      macrophages with F4/80 immunohistochemical-stain, and capsular thickness and
      foreign body giant cells with hematoxylin & eosin. RESULTS: DAPI revealed a
      significantly increased cellularity in both PVA andsilicone, and ePTFE had the
      lowest cell density. Silicone showed the lowest cellularity at d14 and d90
      whereas ePTFE showed the lowest cellularity at days 30, 60, and 180. Masson's
      trichrome staining demonstrated no apparent difference in collagen. Toluidine
      blue showed no differences in mast cells. There were, however, fewer macrophages
      associated with ePTFE. On d14, PVA had highest number of macrophages, whereas
      polypropylene had the highest number at all time points after d14. Giant cells
      increased earlier and gradually decreased later. On d90, PVA exhibited a
      significantly increased number of giant cells compared to polypropylene and
      silicone. Silicone consistently formed the thinnest capsule throughout all time
      points. On d14, cotton had formed the thickest capsule. On d30 polypropylenehas
      formed thickest capsule and on days 60, 90 and 180, PVA had formed thickest
      capsule. CONCLUSION: These data reveal differences in capsule thickness and
      cellular response in an implant-related manor, indicating that fibrotic reactions
      to biomaterials are implant specific and should be carefully considered when
      performing studies on fibrosis when biomaterials are being used.

PMID- 29062168
TI  - Illicium verum Extract and Trans-Anethole Attenuate Ovalbumin-Induced Airway
      Inflammation via Enhancement of Foxp3+ Regulatory T Cells and Inhibition of Th2
      Cytokines in Mice.
AB  - Illicium verum is used in traditional medicine to treat inflammation. The study
      investigates the effects of IVE and its component, trans-anethole (AET), on
      airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. Asthma was
      induced in BALB/c mice by systemic sensitization to OVA, followed by
      intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were
      orally administered for four weeks. We investigated the effects of treatment on
      airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration,
      immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage,
      Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3)
      expression, and lung histology. IVE and AET ameliorated OVA-driven airway
      hyperresponsiveness (p < 0.01), pulmonary eosinophilic infiltration (p < 0.05),
      mucus hypersecretion (p < 0.01), and IL-4, IL-5, IL-13, and CCR3 production (p <
      0.05), as well as IgE levels (p < 0.01). IVE and AET increased Foxp3 expression
      in lungs (p < 0.05). IVE and AET reduced IL-4 and increased IFN-gamma production
      in the supernatant of splenocyte cultures (p < 0.05). Histological studies showed
      that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs (p <
      0.01). These results indicate that IVE and AET exert antiasthmatic effects
      through upregulation of Foxp3+ regulatory T cells and inhibition of Th2
      cytokines, suggesting that IVE may be a potential therapeutic agent for allergic
      lung inflammation.

PMID- 29062169
TI  - Nutrigenomics and Nutrigenetics: New Insight in Disease Prevention and Cure.

PMID- 29062170
TI  - Diseases and Molecular Diagnostics: A Step Closer to Precision Medicine.
AB  - The current advent of molecular technologies together with a multidisciplinary
      interplay of several fields led to the development of genomics, which
      concentrates on the detection of pathogenic events at the genome level. The
      structural and functional genomics approaches have now pinpointed the technical
      challenge in the exploration of disease-related genes and the recognition of
      their structural alterations or elucidation of gene function. Various promising
      technologies and diagnostic applications of structural genomics are currently
      preparing a large database of disease-genes, genetic alterations etc., by
      mutation scanning and DNA chip technology. Further the functional genomics also
      exploring the expression genetics (hybridization-, PCR- and sequence-based
      technologies), two-hybrid technology, next generation sequencing with
      Bioinformatics and computational biology. Advances in microarray "chip"
      technology as microarrays have allowed the parallel analysis of gene expression
      patterns of thousands of genes simultaneously. Sequence information collected
      from the genomes of many individuals is leading to the rapid discovery of single
      nucleotide polymorphisms or SNPs. Further advances of genetic engineering have
      also revolutionized immunoassay biotechnology via engineering of antibody
      encoding genes and the phage display technology. The Biotechnology plays an
      important role in the development of diagnostic assays in response to an outbreak
      or critical disease response need. However, there is also need to pinpoint
      various obstacles and issues related to the commercialization and widespread
      dispersal of genetic knowledge derived from the exploitation of the biotechnology
      industry and the development and marketing of diagnostic services. Implementation
      of genetic criteria for patient selection and individual assessment of the risks
      and benefits of treatment emerges as a major challenge to the pharmaceutical
      industry. Thus this field is revolutionizing current era and further it may open
      new vistas in the field of disease management.

PMID- 29062171
TI  - Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population
      and an Updated Meta-analysis.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate pathway.
      Several polymorphisms were reported in MTHFR gene but C677T polymorphism is most
      studied and it has been reported to be risk factor for several
      diseases/disorders. The present study was designed to explore the frequency of
      MTHFR C677T polymorphism in North Indian healthy population. In addition to this
      a meta-analysis of published articles was also performed to estimate the global
      prevalence of MTHFR C677T polymorphism. A total of 1000 unrelated healthy
      subjects were selected for MTHFR C677T polymorphism analysis. Different databases
      were searched for eligible articles. Prevalence proportion with 95 % CI was used
      to determine global prevalence of T allele and TT genotype. Meta-analysis was
      performed by Open meta-analyst. In 1000 blood samples analyzed, the frequency of
      T allele and TT genotype was 11 and 1 % respectively. Results of the meta
      analysis showed that the global prevalence of T allele and TT genotype were 24.0
      % (95 % CI 21.7-26.5) and 7.7 % (95 % CI 6.5-8.9) respectively. In sub-group meta
      analysis, the lowest frequency of T allele was found in Africans (10.3 %; 95 % CI
      3.8-16.8), and highest in Europeans (34.1 %; 95 % CI 31.9-36.3). The frequency of
      T allele in the North India is 11 %. The results of the meta-analysis showed that
      the frequency of the T allele and the TT genotype of C677T is highest in the
      Caucasian population.

PMID- 29062172
TI  - N-acetyl-l-cysteine Prevents Bile Duct Ligation Induced Renal Injury by
      Modulating Oxidative Stress.
AB  - The aim of the present study was to evaluate the effect of N-acetyl-l-cysteine
      (NAC) on bile duct ligation (BDL) induced oxidative stress in kidneys. Male
      Wistar rats were randomly segregated into four groups; sham control (SC), SC +
      NAC, BDL and BDL + NAC group. Liver damage was induced following BDL and renal
      injury was assessed by kidney function tests along with lipid peroxidation,
      nitrite levels, thiols and antioxidant enzymes. Three weeks after BDL, rats
      developed renal dysfunction in terms of elevated serum creatinine levels. BDL
      animals exhibited an increase in lipid peroxidation, reduction in thiols and
      redox ratio in liver and kidney tissue along with altered antioxidant enzymes in
      kidneys. BDL animals that were orally administered NAC at a daily dose 100 mg/kg
      for duration of two weeks, showed significant reduction in serum creatinine
      levels. NAC was effective in lowering lipid peroxidation and was able to restore
      thiol levels along with GSH/GSSG ratio in both liver and kidneys along with the
      activity of antioxidant enzymes in the kidneys of BDL animals. The results
      clearly demonstrate the efficacy of NAC in attenuating oxidative stress in
      kidneys, suggesting a therapeutic role for NAC in individuals with renal
      dysfunction following BDL.

PMID- 29062173
TI  - Effect of Ethanolic Extract from Seeds or Pods of Xylopia Aethiopica (Dunal) A.
      Rich (Annonaceae) on the Testicular Function of Adult Male Rats.
AB  - Xylopia aethiopica (Annonaceae) is used in some folk medicines and widely
      consumed as a spice in some parts of Nigeria. Its efficacy as an anti-androgenic
      substance has warranted the attention of African scholars. This study evaluated
      the enzymatic activity of lactate dehydrogenase (LDH), gamma-glutamyl transferase
      (gamma-GT), sperm quality (motility, count, morphology), testosterone level and
      histo-pathological changes of the testis of rats chronically treated with
      ethanolic extract of the pods (without seeds), seeds, and fruits (pods + seeds)
      of Xylopia aethiopica. Male Wistar (224-246 g) rats were treated with the extract
      of the pods, seeds, and fruits of Xylopia aethiopica at the dose of 0, 50, 100,
      and 200 mg/kg body wt. for 60 days. Serum biochemistry, sperm quality and histo
      pathological examination of the testis were assessed for any treatment-related
      adverse effects. After treatment with Xylopia aethiopica, testosterone level was
      decreased dose-dependently in the animals treated with the seed extract compared
      to all other groups. The enzymatic activities of LDH and gamma-GT were higher in
      rats treated with the seed and fruit extracts compared with those treated with
      the pods. The numbers of motile sperm, and counts were decreased while the
      numbers of sperm with morphological defects were higher in rats treated with the
      seed and fruit extracts compared to the control. Histopathological changes of the
      testis were also more severe in rats treated with the highest dose of the seed
      extract. We conclude that the compounds related to the anti-infertility effects
      of Xylopia aethiopica are present in the seeds.

PMID- 29062174
TI  - Preventive Efficacy of Vanillic Acid on Regulation of Redox Homeostasis, Matrix
      Metalloproteinases and Cyclin D1 in Rats Bearing Endometrial Carcinoma.
AB  - Endometrial carcinoma is a malignant tumor of the female genital tract. This
      study has been performed to evaluate the chemopreventive efficacy of vanillic
      acid (a bio flavonoid) on endometrial carcinoma (EC) by assessing the levels of
      thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH),
      cytochrome P450, antioxidants-superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxides (GPx), reduced glutathione (GSH), vitamins C and E, matrix
      metalloproteinases (MMP-2 and 9) and cell cycle check point protein (cyclin D1)
      in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induced carcinogenic rats. EC
      provoked by intravaginal detention of MNNG (150 mg/kg b.w. for 90 days), lead to
      enhancement of the levels of TBARS, LOOH, cytochrome P450, and decrement in the
      levels of antioxidants (SOD, CAT, GPx, GSH, vitamins C and E) and upregulated
      expression of MMP-2 and 9 and cyclin D1 (by western blot analysis). The treatment
      of vanillic acid (100 mg/kg b.w.) to MNNG treated rats (1) normalized the
      histopathological alterations, (2) reduced the levels of TBARS, LOOH and
      cytochrome P450 (3) increased the levels of antioxidants (SOD, CAT, GPx, GSH,
      vitamins C and E) in plasma and uterus and (4) down regulated the expression of
      MMP-2, 9 and cyclin D1. The effect of vanillic acid is more predominant in pre
      treatment group than co-treated rats. Our results designate that vanillic acid
      inhibits the EC by elevating antioxidants and by regulating the levels of
      metalloproteinase and cell cycle check point protein.

PMID- 29062175
TI  - A Study on Gene Expression Profile of Endogenous Antioxidant Enzymes: CAT, MnSOD
      and GPx in Dengue Patients.
AB  - Dengue is an arthropod-borne threat among tropical countries. Currently no
      effective means to treat the virus or to predict which patient will develop the
      severe form of the disease. Recently the relationship between
      oxidative/antioxidative response and dengue pathogenesis was suggested. Based on
      this the present study has analysed the expression of endogenous antioxidant
      genes: Catalase (CAT), Superoxide dismutase (MnSOD) and Glutathione peroxidase in
      patients with dengue compared to other febrile illness (OFI) and healthy
      controls. The study enrolled 88 dengue confirmed patients comprising 56 were
      patients with non-severe dengue, and 32 were severe dengue cases, 31 were
      patients with OFI, and 63 healthy controls were also involved. Peripheral blood
      mononuclear cells isolated from patients and controls during the day of admission
      and from the available cases on the day of defervescence were used to estimate
      the transcript levels by quantitative PCR. The expression levels of all the three
      genes were found to be down-regulated throughout the course of dengue infection
      (p < 0.05) and OFI cases compared to healthy controls. Within dengue group, no
      significant difference was observed in any of the parameters between severe and
      non-severe cases. Interestingly, a significant down-regulation of MnSOD
      expression was recorded in secondary dengue infection compared to primary during
      admission (p < 0.05). It was found that all the down-regulated study genes have
      positively correlated in all dengue cases during the day of admission (p < 0.01).
      But during defervescence, the same was found only between CAT and MnSOD. Down
      regulated endogenous antioxidant enzymes during dengue infection could be the
      possible rationale of oxidative stress reported in dengue disease earlier. The
      present study markers could not distinguish dengue from OFI cases and severe from
      non-severe dengue cases. Mechanism of down-regulation has to be explored further
      which will pave the way for the therapeutic target in dengue disease.

PMID- 29062176
TI  - Supplementation of alpha-Tocopherol Attenuates Minerals Disturbance, Oxidative
      Stress and Apoptosis Occurring in Favism.
AB  - The favism is a metabolic disease that characterized with an acute hemolytic
      anemia where alpha-tocopherol is a type of tocopherol accumulated inside the
      human body. The objective of such a study was established to evaluate the effect
      of alpha-tocopherol in favism disorders. A total of 75 human cases were divided
      into 5 groups as follow; group 1 normal cases without any treatment and group 2
      normal cases orally administrated alpha-tocopherol (200 mg/kg) once a day over 30
      days period. Group 3 favism patients without any treatment. Groups 4 and 5 favism
      patients orally administrated 100 and 200 mg alpha-tocopherol/kg, respectively
      once a day over 30 days period. The results obtained revealed that oral
      administration of alpha-tocopherol into normal cases over 30 days period did not
      induce any biological change. In favism, hemoglobin, hematocrit, red and white
      blood cells, serum glucose, glucose-6-phosphate dehydrogenase, total protein,
      albumin, globulin, aspartate and alanine aminotransferases, blood glutathione,
      superoxide dismutase, glutathione peroxidase and serum calcium, phosphorous,
      sodium, potassium and chloride levels were significantly decreased. On the other
      hand, serum alkaline phosphatase, bilirubin, selenium, zinc, manganese, copper
      and iron, malondialdehyde levels showed significant increase in favism.
      Supplementation with alpha-tocopherol into favism restores all the above
      mentioned parameters to approach the normal levels. Also, alpha-tocopherol has
      anti-apoptotic effect in favism. In conclusion, alpha-tocopherol attenuates
      minerals disturbance, oxidative stress and apoptosis occurring in favism.

PMID- 29062177
TI  - Comparative Diagnostic Utility of Neopterin and IFN-gamma/IL-2 in Extrapulmonary
      Tuberculosis.
AB  - Resurgence of TB has emphasized the need for newer methods of diagnosis.
      Extrapulmonary tuberculosis (EPTB), being paucibacillary, is a diagnostic
      dilemma. The aim of the present study was to correlate IFN-gamma/IL-2 with
      neopterin in diagnosis of EPTB. Extrapulmonary specimens from 69 clinically
      diagnosed cases were stained by Ziehl-Neelsen and cultured on Lowenstein-Jensen
      medium for Mycobacterium tuberculosis. ELISA was used to assess serum IFN-gamma,
      IL-2 and neopterin levels. Median serum levels of IFN-gamma/IL-2 and neopterin
      were 3.22 and 21.6 nmol/L in clinically diagnosed EPTB cases and 0.52 and 4.20
      nmol/L in healthy controls respectively (p < 0.001). Both IFN-gamma/IL-2 and
      neopterin were significantly higher in culture positive (14.64 and 49.8 nmol/L)
      than culture negative cases (3.01 and 17.5 nmol/L) respectively (p < 0.05). IFN
      gamma/IL-2 was significantly higher in AFB smear positive cases (8.63) than smear
      negative cases (3.04) (p = 0.003), whereas no significant difference in neopterin
      levels was seen (p = 0.307). A positive correlation between IFN-gamma/IL-2 and
      neopterin was seen in EPTB cases (spearman's rho = 0.453, p < 0.001), whereas in
      healthy controls no such correlation existed (spearman's rho = 0.018, p = 0.884).
      An urgent need for research in the field of biomarkers exists to utilize them as
      point of care test in the diagnosis of EPTB.

PMID- 29062178
TI  - Role of LCAT and Apo A-I in Newly Diagnosed HIV Patients.
AB  - Human immunodeficiency virus (HIV) infection is a growing concern for health
      workers. The two major components of dyslipidemia in HIV infected patients are
      hypertriglyceridemia and decreased levels of high density lipoprotein (HDL) which
      contribute to increased atherosclerotic risk. The study included 150 newly
      diagnosed HIV patients and 150 healthy controls. In all these cases Lecithin
      cholesterol acyl transferase (LCAT) activity was assessed by measuring the
      difference between esterified and free cholesterol by digitonin precipitation
      method and levels of Apolipoprotein A-I (apo A-I) were measured by
      immunoturbidimetric method. There was a significantly decreased LCAT activity (p
      < 0.05) as well as reduced levels of apo A-I (p < 0.05) in newly diagnosed HIV
      patients (54.98 +/- 3.44 IU/L and 131.85 +/- 8.49 mg/dl) when compared with
      healthy controls (88.17 +/- 14.36 IU/L and 187.05 +/- 35.25 mg/dL). A significant
      positive correlation (r = 0.7406) was found between LCAT activity and apo A-I
      levels. In conclusion decreased LCAT activity and decreased levels of apo A-I
      reduce the reverse cholesterol transport in newly diagnosed HIV patients which
      may lead to atherosclerosis in the future.

PMID- 29062179
TI  - Determining Serum Zinc and Magnesium Levels in Hemodialysis Patients Could be
      Helpful for Clinicians.
AB  - Trace element determination is requested rarely for critically ill patients in
      Iran, due to the underestimation of the trace element determination by Iranian
      physicians. The aim was to compare the levels of Zn and Mg in a group of
      hemodialysis patients and normal individuals. This study shows that trace element
      determination is helpful for management of hemodialysis patients. Fifty-three
      hemodialysis patients and 51 control individuals were randomly analyzed for Zn
      and Mg serum levels. Comparison of before or after dialysis and with normal
      individuals was done and receiver operating characteristics (ROC) curves were
      plotted to evaluate the analytical sensitivity and specificity of Zn and Mg
      determination. Confidence interval for all statistical methods was 95 %. Zinc
      serum levels were decreased after hemodialysis insignificantly (P = 0.201) but Mg
      levels were decreased significantly (P = 0.000). Both Zn and Mg levels, before
      and after hemodialysis were meaningfully lower than normal controls (P < 0.05).
      ROC analysis showed that the area under the curve was high for Zn levels both
      before and after hemodialysis but it was high for Mg only before hemodialysis.
      Current study shows that serum Zn and Mg measurements can have clinical
      importance. Both before and after hemodialysis, serum Zn = 297.5 ug/L and Mg =
      2.295 ug/L are proposed as cut-off values with about 90 % specificity, for
      monitoring of these two element in hemodialysis patients. It is suggested that
      clinicians consider the measurement of these trace elements for hemodialysis
      patients routinely or periodically as clinical chemistry tests.

PMID- 29062180
TI  - Evaluation of Metabolic Syndrome and Vitamin D Receptor Gene Polymorphism in Male
      Factor Infertility.
AB  - Male factor infertility (MFI) is a growing health issue in society. The vitamin D
      receptor gene (VDR) is expressed in many tissues and modulates expression of
      several other genes. The purpose of this study was to investigate the association
      between MetSyn, VDR gene (FokI, rs-2228570; C > T) polymorphisms and MFI in
      Indian adults. Fifty cases and fifty-four controls, fulfilling inclusion and
      exclusion criteria, were included with their informed consent. Fasting plasma
      glucose, triglyceride, HDL-C were estimated by clinical chemistry analyzer
      (Beckmam Coulter DXC 800, USA). Serum insulin was measured by
      electrochemiluminescence immunoassay and VDR gene polymorphism by RFLP-PCR.
      Statistical analysis was done using SPSS 20.0. MetSyn was more frequent in MFI
      cases than controls. There was significant difference between waist
      circumference, fasting plasma glucose, triglycerides in MFI cases and controls.
      There was significant difference in HOMA-IR between MFI cases and controls (p
      value < 0.05) and serum insulin was significantly raised in MFI cases (p value <
      0.05). VDR gene polymorphism was found to be associated with MFI cases as
      compared to controls and the serum level of vitamin D was also decreased in MFI
      cases than in controls (p value < 0.05). This study provides evidence that
      insulin resistance is more in MFI cases than in controls and occurrence of MetSyn
      and its components is higher in MFI cases than in controls. Our findings provide
      evidence that VDR gene (FokI, rs-2228570; C > T) polymorphism increases the risk
      of male factor infertility.

PMID- 29062181
TI  - Micronutrients Drift During Daily and Weekly Iron Supplementation in Non-anaemic
      and Anaemic Pregnancy.
AB  - AIMS: Pregnancy is a phenomenon associated with dynamic changes in physical,
      mental and biochemical status of body and demands increased nutritional intake
      for developing foetus. The level of various micronutrients which act as co
      factors for antioxidant enzymes or it-self as antioxidants gets altered with the
      progression of pregnancy. The present longitudinal study summarized the trend of
      selected micronutrients level in anaemic (AP) and non-anaemic primigravida (NAP)
      supplemented with daily and weekly oral iron folic acid (IFA) tablet during
      pregnancy and postpartum. METHODS: A total of 200 primigravida {N = 100; NAP (Hb
      > 11 g/dl) and N = 100 AP (Hb = 8-11 g/dl) assigned daily (N = 50) and weekly (N
      = 50) supplementation} were recruited and overnight fasting blood samples were
      withdrawn at 13-16 weeks, after 3 months and 6 weeks postpartum. The serum iron,
      copper, zinc, magnesium and manganese were estimated by inductively coupled
      plasma-atomic emission spectrophotometer. RESULTS: Serum manganese (p < 0.05) at
      baseline and magnesium (p < 0.01) at postpartum was significantly different
      between NAP and AP supplemented with daily IFA tablets. The trend of copper found
      to be increased during pregnancy and later declined at postpartum in both the
      groups. Daily supplementation resulted in significantly high iron (p < 0.05) in
      NAP during third trimester. CONCLUSIONS: Hypozincemia and hypomagnesemia was
      observed in anaemic pregnancy supplemented with weekly and daily IFA
      respectively. Clear evidence of altered micronutrients levels during healthy and
      anaemic pregnancy was seen. The reference values may be drawn from this study for
      the nutritional assessment during pregnancy for healthy pregnancy outcomes. TRIAL
      REGISTRATION: Clinical Trial Registry-India, http://ctri.nic.in,
      CTRI/2014/10/005135.

PMID- 29062182
TI  - "Metabolic Syndrome and Its Risk Determinants in Sikkim": A Glimpse from a
      Hospital Study.
AB  - Sikkim has been reported to have the highest percentage of Diabetes Mellitus and
      Hypertension in the country. The study aimed to focus its precursor termed
      'Metabolic Syndrome' (MetS) with special attention to its risk determinants as a
      measure to promote awareness in preventing the rise in number of these non
      communicable diseases in the state with only 6,10,577 inhabitants. Of 361
      participants, 33.5% were diagnosed MetS as per the harmonized MetS criteria,
      64.5% deemed non-MetS comprised of participants with "2 Risk", "1 Risk" and "0
      Risk" for MetS, however not enough (3 or more) to be categorized as MetS. A
      "large WC + elevated BP + raised FBS"; "large WC + elevated BP" and "large WC"
      were the different types of risk combinations found frequently in the "3 Risk",
      "2 Risk" and "1 Risk" category respectively. MetS was most common among the
      females and highly found in 51-60 years of age. Ethnically
      "Bhutia/Lepcha/Tamang/Sherpa" were diagnosed with highest percentage of MetS
      followed by "Nepalese" and "Others". The chief contributing factor to compose
      MetS in the female population was a large WC. We conclude, Diabetes and
      Hypertension are indeed prevailing in Sikkim and that the presence of either an
      increased waist circumference or an elevated blood pressure mandates a check for
      the remaining four risk factors for MetS, rendering worthwhile to keep an account
      of MetS risk types by stratification to comprehend the influence of socio
      cultural and ethno-geographical factors in causing MetS.

PMID- 29062183
TI  - Erythrocyte Membrane Bound ATPase and Antioxidant Enzyme Changes Associated with
      Vascular Calcification is Reduced by Sodium Thiosulfate.
AB  - Sodium thiosulfate (STS), a cyanide antidote has been reported to possess
      antioxidant and calcium chelation effects, useful for the treatment of renal
      failure due to vascular calcification and urolithiasis. The present study
      investigated the in vivo modulatory effects of STS on erythrocyte calcium,
      phosphorous levels, lipid peroxidation, antioxidant enzyme and membrane ATPase
      activities (Ca2+, Na+K+, Mg2+ and 5'' nucleotidase) in an adenine induced model
      of vascular calcification in rats. Adenine (0.75%) was supplemented through the
      diet for 28 days, which resulted in significantly (P < 0.05) increased
      circulating calcium and phosphorous product and oxidative stress within the RBCs,
      as measured from lipid peroxidation and reduced antioxidant enzymes. The membrane
      ATPase activities were altered (increased Ca2+, Na+K+ ATPase and decreased Mg+
      ATPase, 5' nucleotidase) compared to the rats fed on normal diet. STS (400 mg/kg)
      given orally was effective in establishing a normalcy in the RBC alterations.
      This effect was more pronounced, when STS was given from day 28 to day 49 after
      induction of calcification, instead of day 0 to day 28. These findings may
      benefit to evaluate the effectiveness of STS therapy in patients with chronic
      renal failure associated with increased circulating calcium and phosphorous
      product that leads to stiffening of vascular smooth muscles of aorta, due to
      calcium deposition.

PMID- 29062184
TI  - A Case of Massive Hypertriglyceridemia in 6 Year Old Boy.
AB  - Type V hypertriglyceridemia in children is a rare condition since it has often
      been associated with obesity, type II diabetes, metabolic syndrome and hormone
      therapy. We encountered a case of massive hypertriglyceridemia (1900 mg/dl) in a
      6 years old boy with complains of acute pancreatitis but no physical
      manifestations. There was no family history of sudden cardiac death, father and
      younger male sibling were found to be normal. The mother however had
      hypertriglyceridemia. The child was managed by dietary changes, omega 3 capsules
      and low dose fenofibrate. On follow up showed there was reduction in lipid
      profile and lipoprotein electrophoretic pattern showed bands for VLDL and
      chylomicron indicating type V hyperlipidemia. Early diagnosis via screening for
      lipid profile of such patients and their family can improve prognosis and quality
      of life of these children.

PMID- 29062185
TI  - A Case of Renal Tubular Acidosis with Sjogren's Syndrome Showing Paradoxical
      Block of PTH Due to Severe Hypomagnesemia.
AB  - Distal renal tubular acidosis (RTA) manifests either as Complete/Classical form
      or Incomplete/Latent Form. Distal RTA causes normal anion gap metabolic acidosis
      and hypokalemia. Interstitial Nephritis is the most frequent renal manifestation
      of Sjogren's, which presents as Distal RTA in 25-40% of patients with Sjogren's
      syndrome. Magnesium deficiency is frequently associated with hypokalemia.
      Although serum calcium is the main physiological control for the secretion of
      parathyroid hormone (PTH) by the parathyroid, serum magnesium can also exert
      similar effects. While low levels of magnesium stimulate the secretion of PTH,
      very low serum concentrations tend to induce a paradoxical block of PTH release
      by activation of the alpha-subunits of heterotrimeric G-proteins. This mimicks
      the activation of calcium sensing receptor leading to inhibition of PTH
      secretion. Here we describe the case history of a 35-year-old lady who presented
      to our hospital with severe hypokalemia due to distal RTA and perhaps had a
      paradoxical block of PTH secretion in the setting of severe hypomagnesemia.

PMID- 29062186
TI  - Lead Poisoning Due to Herbal Medications.
AB  - Many herbal products are harmless or possess minimal toxicity, whereas, some
      contain toxic ingredients that may not be identified due to lack of quality
      control or not listed on the label. Over the years, several case reports and
      studies have documented that herbal medications may contain ingredients that are
      toxic. Several studies have documented that some herbal medications contained
      high concentrations of heavy metals, such as lead, mercury, and arsenic.
      Publications of such case reports and studies have repeatedly reminded us that we
      have failed in our legal and civic duties of educating users of herbal
      medications and general population about the grave concerns posed by the herbal
      medications and their associated toxicities.

PMID- 29062188
TI  - Electrocardiographic reference values and configuration of electrocardiogram
      waves recorded in Black Bengal goats of different age groups.
AB  - AIM: A study on age-related electrocardiographic (ECG) changes was conducted on
      20 apparently healthy Black Bengal goats with no history of cardiac disorders
      during 2015-2016. MATERIALS AND METHODS: The goats selected for the study
      belonged to four different age groups; Group 1: Goats up to 6 months of age,
      Group 2: Above 6 months and below 1 year of age, Group 3: Above 1 year and below
      2 years of age, and Group 4: Above 2 years of age. The ECG was recorded with the
      animals in standing position using a 12-lead standard ECG recorder (Model
      Cardiart-108 MK VII, manufactured by BPL, India). The paper speed was set to 25
      mm/s with the sensitivity of the machine was adjusted at 1 (1 cm=mV). RESULTS:
      The ECG parameters were compared within different age groups, and the data were
      analyzed statistically using SPSS 16.0 taking a significant level of 95% (p<0.05)
      in all cases. The lead-I ECG revealed a significant difference in amplitude of
      QRS complex, PR interval, QT interval, RR interval, PQ segment, ST segment, TP
      segment, and heart rate among some age groups. In bipolar limb lead-II, the
      amplitude of T-wave, RR interval, ST segment, TP segment, and heart rate was a
      significant difference among some age groups. Lead-III presented significant
      difference among age groups in different parameters such as QRS complex duration,
      T-wave duration, RR interval, ST segment, TP segment, and heart rate. CONCLUSION:
      The study concluded that there is a significant variation in the ECG parameters
      both in terms of values and configuration of ECG waves when age is taken into
      consideration. The results of the study might be used as a reference value for
      field veterinarians.

PMID- 29062187
TI  - Acute toxicity of commercial atrazine in Piaractus mesopotamicus:
      Histopathological, ultrastructural, molecular, and genotoxic evaluation.
AB  - AIM: The aim of this work was to evaluate the sensitivity of Pacu fingerlings
      (Piaractus mesopotamicus) by measuring the effects of median lethal concentration
      (LC50) of atrazine (ATZ - 28.58 mg/L) after acute exposure (up to 96 h).
      MATERIALS AND METHODS: The fish were exposed to the LC50 of ATZ for 96 h (28.58
      mg/L) in a static system. During the experiment, the fingerlings were randomly
      distributed in four glass tanks (50 L) containing dechlorinated water. Four glass
      tanks were for the control group, and four were for the ATZ-exposed group (n=4
      per glass tank), given a total number of 16 animals tested per group. The
      genotoxicity was evaluated by micronucleus (MN) test in erythrocytes from
      peripheral blood. Qualitative and semi-quantitative histopathological analyses,
      and also ultrastructural study, were applied in liver and kidney samples.
      Finally, the content of heat shock protein (Hsp70) in the liver was evaluated by
      the western blotting method. RESULTS: The morphological alterations in the liver,
      which was associated with increased expression of Hsp70, included nuclear and
      cytoplasmic vacuolization, cytoplasmic hyaline inclusions, and necrosis. The
      kidney presented edema and tubular cell degeneration with cytoplasmic hyaline
      inclusion. The semi-quantitative histopathological analyses indicated that the
      liver was more sensitive than kidney to ATZ-induced damage. Ultrastructural
      analysis showed that ATZ caused membrane alterations in several organelles and
      increased the number of lysosomes in hepatocytes and kidney proximal tubular
      cells. Nevertheless, no significant difference was observed in MN frequency in
      erythrocytes comparing treated and control groups. CONCLUSION: These results
      indicated that ATZ-induced damage to the kidney and liver function, ATZ at the
      concentration tested did not induce a significant difference in MN frequency in
      Pacu erythrocytes comparing treated and control groups, and also that Pacu
      fingerlings may be a good bioindicator for testing freshwater contamination.

PMID- 29062189
TI  - Zoo agent's measure in applying the five freedoms principles for animal welfare.
AB  - BACKGROUND: Animal welfare should be prioritized not only for the animal's life
      sustainability but also for supporting the sustainability of living organism's
      life on the earth. However, Indonesian people have not understood it yet, thereby
      still treating animals arbitrarily and not appreciating either domesticated or
      wild animals. AIM: This research aimed to analyze the zoo agent's action in
      applying the five freedoms principle for animal welfare in Taman Satwa Taru Jurug
      (thereafter called TSTJ) or Surakarta Zoo and Gembira Loka Zoo (GLZ) of
      Yogyakarta Indonesia using Giddens structuration theory. MATERIALS AND METHODS:
      The informants in this comparative study with explorative were organizers,
      visitors, and stakeholders of zoos selected using purposive sampling technique.
      The informants consisted of 19 persons: 8 from TSTJ (Code T) and 10 from GLZ
      (Code G) and representatives from Natural Resource Conservation Center of Central
      Java (Code B). Data were collected through observation, in-depth interview, and
      Focus Group Discussion and Documentation. Data were analyzed using an interactive
      model of analysis consisting of three components: Data reduction, data display,
      and conclusion drawing. Data validation was carried out using method and data
      source triangulations. RESULTS: Food, nutrition, and nutrition level have been
      given consistent with the animals' habit and natural behavior. Animal keepers
      always maintain their self-cleanliness. GLZ has provided cages according to the
      technical instruction of constructing ideal cages, but the cages in TSTJ are
      worrying as they are not consistent with standard, rusty, and damaged, and
      animals have no partner. Some animals in GLZ are often sick, whereas some animals
      in TSTJ are dead due to poor maintenance. The iron pillars of cages restrict
      animal behavior in TSTJ so that they have not had freedom to behave normally yet,
      whereas, in GLZ, they can move freely in original habitat. The animals in the two
      zoos have not been free from disruption, stress, and pressure due to the passing
      over vehicles. CONCLUSION: There should be strategic communication, information,
      and education, community development, and law enforcement for the animal welfare.

PMID- 29062190
TI  - Detection of Toxoplasma gondii in cat's internal organs by immunohistochemistry
      methods labeled with-[strept] avidin-biotin.
AB  - AIM: The aims of the study are to detect the presence of Toxoplasma gondii
      antigen and to determine its distribution location in several organs of domestic
      cat using immunohistochemistry (IHC) method with Labeled-[Strept] Avidin-Biotin
      (LAB-SA). MATERIAL AND METHODS: Four domestic cats aged 1-2 years were used as
      sample in this research. The sample divided into two groups with two cats each.
      Cats in Group I were positive Toxoplasma based on serologically screening test,
      while cats in Group II were orally infected with 1*106Toxoplasmaoocyst. All
      samples then necropsied, and the organs including brain, liver, kidney, duodenum,
      jejunum, ileum, lungs, and spleen were collected for IHC method with LAB-SA.
      RESULT: The result showed that Toxoplasma antigens were detected in ileum of both
      serologically positive domestic cat and the experimentally infected cats.
      Toxoplasma was also observed in kidney of serologically positive domestic cat. In
      the serologically positive domestic cat, necrotic lesions were found on ileum,
      kidney, and liver, whereas in experimentally infected cat, the lesion was only
      found on ileum. CONCLUSION: The presence of Toxoplasma antigen is successfully
      detected in several organs of domestic cat using IHC method with the LAB-SA.

PMID- 29062191
TI  - Detection of food-borne bacteria in ready to eat betel leaf sold at local markets
      in Mymensingh.
AB  - AIM: The present study was undertaken to determine bacterial load as well as
      characterize bacterial flora of ready to eat (RTE) betel leaf sold at local
      markets in Mymensingh city. MATERIALS AND METHODS: A total of 25 RTE betel leaf
      samples were collected from five local markets such as Kamal-Ranjit (KR) market,
      Shesh more, Kewatkhali, Jobber more, and Ganginar par. RESULTS: Total viable
      count of bacteria in betel leaf (log10 mean colony forming unit+/-standard
      deviation/ml) was 7.58+/-0.04 for KR market, 7.72+/-0.06 for Shesh more, 7.62+/
      0.04 for Kewatkhali, 7.40+/-0.03 for Jobber more, and 7.60+/-0.06 for Ganginar
      par. A total of 98 bacterial isolates belong to five genera (Escherichia coli,
      Salmonella spp., Vibrio spp., Bacillus spp., and Staphylococcus spp.) were
      identified. The prevalence of E. coli was 17.34%, Salmonella spp. was 25.51%,
      Vibrio spp. was 19.39%, Bacillus spp. was 18.37%, and Staphylococcus spp. was
      19.39%. Antibiotic sensitivity test showed that all isolates were sensitive to
      two antibiotics such as ciprofloxacin and gentamicin. Four isolates (E. coli,
      Salmonella spp., Vibrio spp., and Staphylococcus spp.) were resistant to two
      antibiotics (ampicillin and cephalexin). Antibiogram profile of bacterial
      isolates of betel leaf suggests that they were multidrug resistance. CONCLUSION:
      Data of this study indicate that betel leaf sold at local market harbors
      multidrug resistance food-borne bacteria which might cause public health hazards
      if these antibiotic resistant transfer to human through food chain.

PMID- 29062192
TI  - Hydrophilic nanosilica as a new larvicidal and molluscicidal agent for
      controlling of major infectious diseases in Egypt.
AB  - AIM: This research was conducted to evaluate the molluscicidal and mosquitocidal
      efficacy of silica nanoparticles in the eradication of the larvae and pupa of
      malaria and filariasis vector as well as vectors of rift-valley fever virus
      (Culex pipiens); Schistosoma mansoni vector and Biomphlaria alexandrina (snail
      and egg masses). MATERIALS AND METHODS: Hydrophilic nanosilica particles (NSPs)
      were characterized using transmission electron microscope during the preliminary
      part of the study; the stages were exposed to upgrade concentrations of NSP from
      50 to 1200 ppm each for 24-36 h exposure time. The highly effective
      concentrations were re-evaluated at lower exposure time as 3, 6, and 12 h.
      RESULTS: Lethal concentration (LC50) and LC90 versus mosquito larvae were (350
      ppm/24 h and 1400 ppm/24 h, respectively). C. pipiens pupae proved slight high
      tolerance versus the effect of these nanoparticles as the two previous doses
      increased to 680 ppm/6 h and 1300 ppm/24 h. The LC50 and LC90 versus B.
      alexandrina were increased to 590 ppm/6 h and 980 ppm/48 h, respectively.
      Moreover, the embryonated snail egg masses appear more susceptible to the toxic
      effect of these nanoparticles than the non-embryonated eggs as the LC50 and LC90
      were increased to 1450 ppm/12 h and 1250 ppm/48 h, respectively, for embryonated
      eggs, and it was 1400 ppm/24 h and 1890 ppm/48 h, respectively, for non
      embryonated one. CONCLUSION: The results open a new field for controlling the
      infectious diseases through eradication of their vectors by the way that avoids
      the resistance recorded from the successive chemical application in this field.

PMID- 29062193
TI  - Application of radio frequency based digital thermometer for real-time monitoring
      of dairy cattle rectal temperature.
AB  - AIM: Dairy cattle health monitoring program becomes vital for detecting the
      febrile conditions to prevent the outbreak of the animal diseases as well as
      ensuring the fitness of the animals that are directly affecting the health of the
      consumers. The aim of this study was to validate real-time rectal temperature
      (RT) data of radio frequency based digital (RFD) thermometer with RT data of
      mercury bulb (MB) thermometer in dairy cattle. MATERIALS AND METHODS: Two
      experiments were conducted. In experiment I, six female Jersey crossbred cattle
      with a mean (+/-standard error of the mean) body weight of 534.83+/-13.90 kg at
      the age of 12+/-0.52 years were used to record RT for 2 h on empty stomach and 2
      h after feeding at 0, 30, 60, 90, and 120 min using a RFD thermometer as well as
      a MB thermometer. In experiment II, six female Jersey crossbred cattle were
      further used to record RT for 2 h before exercise and 2 h after exercise at 0,
      30, 60, 90, and 120 min. Two-way repeated measures analysis of variance with post
      hoc comparisons by Bonferroni test was done. RESULTS: Real-time RT data recorded
      by RFD thermometer as well as MB thermometer did not differ (p>0.05) before and
      after feeding/exercise. An increase (p<0.05) in RT after feeding/exercise in
      experimental crossbred cattle was recorded by both RFD thermometer and MB
      thermometer. CONCLUSION: The results obtained in the present study suggest that
      the body temperature recordings from RFD thermometer would be acceptable and thus
      RFD thermometer could work well for monitoring real-time RT in cattle.

PMID- 29062194
TI  - Mastitis vaccines in dairy cows: Recent developments and recommendations of
      application.
AB  - The objective of this review article was to summarize the most recent clinical
      field trials that have been published evaluating the use of different types of
      vaccines against mastitis pathogens in dairy cows. Mastitis is one of the most
      common and economically important diseases in dairy cows in the world. The
      disease is considered an important welfare issue facing the dairy industry in
      addition to the loss of production and premature removal or death of affected
      cows. Losses are also related to high cost of veterinary medicines and the cost
      of unsalable milk of treated cows. Mastitis can be caused by either contagious or
      environmental pathogens both of which are best prevented rather than treated. In
      addition to the application of best management practices in the parlor during
      milking, vaccination against common udder pathogens is widely practiced in many
      dairy farms to prevent or reduce the severity of clinical mastitis. In this
      review, the most recent clinical field studies that evaluated the use of
      different types of vaccines in dairy cows are summarized.

PMID- 29062195
TI  - Detection of anti-Toxoplasma gondii antibodies in chronic myeloid leukemia and
      acute myeloid leukemia patients.
AB  - IN: Background and Aim: Infection of Toxoplasma gondii is a worldwide
      distribution. Toxoplasmosis in patients who are immunocompromised by virtue of
      underlying leukemia disease has received relatively little attention. This study
      was aimed to evaluate IgG and IgM antibodies of T. gondii and to minimize the
      role of T. gondii and opportunistic infection complication at the early stage of
      infection in leukemia patients. MATERIALS AND METHODS: The purpose of this assay
      was to measure anti-T. gondii IgG and IgM antibodies by enzyme-linked
      immunosorbent assay (ELISA) technique in leukemia patients. RESULTS: IgG
      antibodies against T. gondii were detected by ELISA in 96 (56.4%) leukemia
      patients and 72 (42.4%) control group. IgM antibodies were found in 10 patients
      (5.9%) with leukemia and 3 (1.8%) in the corresponding. CONCLUSION: Our finding
      indicated that leukemia patients under immunosuppressive condition should not be
      neglected. Toxoplasmosis in leukemia patients as a main risk factor is
      considered, meanwhile in some patients, due to possibility of the presence of
      secondary infection that leads to severe toxoplasmosis.

PMID- 29062196
TI  - Pathology and immunohistochemistry study of Newcastle disease field case in
      chicken in Indonesia.
AB  - AIM: The aim of the study was to examine pathology and the distribution pattern
      of Newcastle disease virus (NDV) in internal organs of chickens from a field case
      using immunohistochemical staining. MATERIALS AND METHODS: 10 groups of broiler,
      layer, and domestic chicken were collected from necropsy room Division of
      Pathology, Bogor Agricultural University. These chickens were originated from
      West Java and collected based on pathologist diagnosis as suspect of Newcastle
      disease (ND). They were subsequently confirmed positive of ND with real-time
      reverse transcription polymerase chain reaction assay. The respiratory,
      circulatory, digestive, lymphoreticular and central nervous systems were
      collected for histopathology examination. RESULTS: The gross pathology and
      histopathology changes were tracheitis, pneumonia, pericarditis, myocarditis,
      catarrhal proventriculitis, catarrhal enteritis, typhlitis, perihepatitis,
      pancreatitis, nephritis interstitial, splenitis, atrophy of Bursa Fabricius, and
      encephalitis. CONCLUSION: The distribution pattern of NDV in internal organs of
      chickens from a field case in this study is similar with a previous reported
      pattern in systemic cases of the internal chicken organs. High intensity of
      immunohistochemistry stain result was detected in trachea, lung, proventriculus,
      duodenum, cecal tonsil, kidney, and brain.

PMID- 29062197
TI  - N-terminal-pro brain natriuretic peptides in dogs and cats: A technical and
      clinical review.
AB  - Biomarkers are quantitative indicators of biological processes performed by an
      organ or system. In recent years, natriuretic peptides (NPs) have emerged as
      important tools in the diagnosis and therapeutic monitoring of heart diseases.
      Research has shown that serum and plasma levels of N-terminal pro brain NP (NT
      proBNP) in dogs and cats are the only biomarkers that afford to diagnose and
      monitor congestive processes and, indirectly, the myocardial function of small
      animals. The present review discusses the peer-reviewed specialized literature
      about NT-proBNP and presents and compares the potential clinical applications of
      this NP in veterinary medicine of small animals, considering diagnosis, follow
      up, and prognosis of myocardial or systemic diseases. The relevance of NT-proBNP
      is associated with sample stability, easy determination in laboratory,
      sensitivity, accuracy, and the possibility to analyze myocardial function. These
      advantages are specially important when NT-proBNP is compared with other cardiac
      biomarkers, mostly those that indicate the integrity of the myocardial cell. Fast
      NT-proBNP assays are marketed today and may be used in association with
      complementary tests. Together, these methods are an important source of
      information in differential diagnosis of heart and lung diseases as well in the
      early diagnosis of cardiopathy in dogs and cats, proving valuable tools in
      treatment and prognosis.

PMID- 29062198
TI  - Matrix-assisted laser desorption-ionization-time-of-flight mass spectrometry as a
      reliable proteomic method for characterization of Escherichia coli and Salmonella
      isolates.
AB  - AIM: Identification of pathogenic clinical bacterial isolates is mainly dependent
      on phenotypic and genotypic characteristics of the microorganisms. These
      conventional methods are costive, time-consuming, and need special skills and
      training. An alternative, mass spectral (proteomics) analysis method for
      identification of clinical bacterial isolates has been recognized as a rapid,
      reliable, and economical method for identification. This study was aimed to
      evaluate and compare the performance, sensitivity and reliability of traditional
      bacteriology, phenotypic methods and matrix-assisted laser desorption-ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) in the identification of clinical
      Escherichia coli and Salmonella isolates recovered from chickens. MATERIALS AND
      METHODS: A total of 110 samples (cloacal, liver, spleen, and/or gall bladder)
      were collected from apparently healthy and diseased chickens showing clinical
      signs as white chalky diarrhea, pasty vent, and decrease egg production as well
      as freshly dead chickens which showing postmortem lesions as enlarged liver with
      congestion and enlarged gall bladder from different poultry farms. RESULTS:
      Depending on colonial characteristics and morphological characteristics, E. coli
      and Salmonella isolates were recovered and detected in only 42 and 35 samples,
      respectively. Biochemical identification using API 20E identification system
      revealed that the suspected E. coli isolates were 33 out of 42 of colonial and
      morphological identified E. coli isolates where Salmonella isolates were
      represented by 26 out of 35 of colonial and morphological identified Salmonella
      isolates. Serological identification of isolates revealed that the most
      predominant E. coli serotypes were O1 and O78 while the most predominant
      Salmonella serotype of Salmonella was Salmonella Pullorum. All E. coli and
      Salmonella isolates were examined using MALDI-TOF MS. In agreement with
      traditional identification, MADI-TOF MS identified all clinical bacterial samples
      with valid scores as E. coli and Salmonella isolates except two E. coli isolates
      recovered from apparently healthy and diseased birds, respectively, with recovery
      rate of 93.9% and 2 Salmonella isolates recovered from apparently healthy and
      dead birds, respectively, with recovery rate of 92.3%. CONCLUSION: Our study
      demonstrated that Bruker MALDI-TOF MS Biotyper is a reliable rapid and economic
      tool for the identification of Gram-negative bacteria especially E. coli and
      Salmonella which could be used as an alternative diagnostic tool for routine
      identification and differentiation of clinical isolates in the bacteriological
      laboratory. MALDI-TOF MS need more validation and verification and more study on
      the performance of direct colony and extraction methods to detect the most
      sensitive one and also need using more samples to detect sensitivity,
      reliability, and performance of this type of bacterial identification.

PMID- 29062199
TI  - Immunological and histopathological changes in sheep affected with cutaneous
      squamous cell carcinoma and treated immunotherapeutically.
AB  - BACKGROUND AND AIM: Recently, it has been recorded unexpected percentage of
      cutaneous squamous cell carcinoma (cSCC) in sheep. Despite the improvement in
      surgical treatment, the outcome of animals remains limited by metastatic relapse.
      Although antibodies for cancer treatment have been practiced for many decades,
      the use of this methodology in animals is deficient. This study aimed to
      establish cSCC therapy by tumor cell protein antibody (Ab1) or secondary antibody
      (Ab2) raised by two series of immunization in the same strain of rabbits.
      MATERIALS AND METHODS: A total of 19 Ossimi sheep were used (14 sheep suffered
      from cSCC and 5 were apparently healthy). Each animal from control healthy group
      (n=5) and control cSCC (n=4) group was treated with a course of eight injections
      of normal globulins. Animals in the third (n=5) and the last (n=5) groups
      received a course of eight injections of Ab1and Ab2, respectively. Each tumor was
      measured before and after treatment. The eight injections were applied at 1st,
      3rd, 5th, 7th, and 9th week and the remaining three injections were at 1 week
      interval. Tissue specimens and blood samples were taken for histological and
      immunological studies. RESULTS: The obtained results revealed that injection of
      Ab1 might prevent the bad prognostic picture of polymorph infiltration without
      any criteria of regression % of tumor. Treatment with Ab2 showed regression of
      tumor size ranged between minimum of 8.99% and maximum of 78.12%, however, the
      measurements in most cases reached the maximum regression after the past two
      injections. In additions, infiltration of lymphocytes to tumor site,
      normalization of leukocytes picture and also increase of antibody titer were
      observed. CONCLUSION: This profile might confirm that Ab2 could act as an antigen
      and encourage us to use it as a tumor vaccine. Extensive studies are needed to
      isolate the idiotypic portion of Ab1 for raising Ab2 as an anti-idiotypic
      antibody to be used as tumor vaccine. The question of how lymphocyte traffic to
      the tumor site as a result of Ab2 injection needs further investigation.

PMID- 29062200
TI  - Cloning and sequence analysis of hyaluronoglucosaminidase (nagH) gene of
      Clostridium chauvoei.
AB  - AIM: Blackleg disease is caused by Clostridium chauvoei in ruminants. Although
      virulence factors such as C. chauvoei toxin A, sialidase, and flagellin are well
      characterized, hyaluronidases of C. chauvoei are not characterized. The present
      study was aimed at cloning and sequence analysis of hyaluronoglucosaminidase
      (nagH) gene of C. chauvoei. MATERIALS AND METHODS: C. chauvoei strain ATCC 10092
      was grown in ATCC 2107 media and confirmed by polymerase chain reaction (PCR)
      using the primers specific for 16-23S rDNA spacer region. nagH gene of C.
      chauvoei was amplified and cloned into pRham-SUMO vector and transformed into
      Escherichia cloni 10G cells. The construct was then transformed into E. cloni
      cells. Colony PCR was carried out to screen the colonies followed by sequencing
      of nagH gene in the construct. RESULTS: PCR amplification yielded nagH gene of
      1143 bp product, which was cloned in prokaryotic expression system. Colony PCR,
      as well as sequencing of nagH gene, confirmed the presence of insert. Sequence
      was then subjected to BLAST analysis of NCBI, which confirmed that the sequence
      was indeed of nagH gene of C. chauvoei. Phylogenetic analysis of the sequence
      showed that it is closely related to Clostridium perfringens and Clostridium
      paraputrificum. CONCLUSIONS: The gene for virulence factor nagH was cloned into a
      prokaryotic expression vector and confirmed by sequencing.

PMID- 29062201
TI  - Cloning and expression of P67 protein of Mycoplasma leachii.
AB  - AIM: The present study was undertaken to clone, express and study the
      immunogenicity of P67 protein of Mycoplasma leachii. MATERIALS AND METHODS: P67
      gene was amplified from genomic DNA of M. leachii. The polymerase chain reaction
      (PCR) product was inserted in pRham N-His SUMO Kan vector and was used to
      transform competent Escherichia cloni 10G cells. Recombinant protein expression
      was done by inducing cells with 0.2% Rhamnose. Purification was done using nickel
      nitrilotriacetic acid affinity chromatography. Western blot and dot blot analysis
      were performed to assess the immunoreactivity of P67 protein. RESULTS: PCR
      amplicon size of P67 gene was found to be 1500 base pair. The size of the fusion
      protein with SUMO tag was 79 kDa in sodium dodecyl sulfate polyacrylamide gel
      electrophoresis analysis. The recombinant P67 fusion protein expressed in pRham N
      His SUMO Kan vector was found to be immunogenic in both western blot and dot blot
      analysis. CONCLUSION: Western blot and dot blot analysis of P67 protein of M.
      leachii revealed that the protein is immunogenic. Further work is needed to
      evaluate the role of P67 antigen of M. leachii as an immunodiagnostic agent.

PMID- 29062202
TI  - The effect of eggshell thickness on hatchability of quail eggs.
AB  - BACKGROUND AND AIM: The aim of the successful incubation period is to achieve
      maximum health chicks in each batch. Therefore, all factors affecting incubation
      have to be investigated in detail. This study investigated the effect of eggshell
      thickness on hatchability of quail eggs. MATERIALS AND METHODS: A total of 1415
      eggs were collected from the same flock at the ages of 23 and 41 weeks. Two
      different incubations were performed at these eggs. Eggshell thicknesses of all
      eggs were determined with an ultrasonic gauge before incubation. Incubation
      period was applied as for 18 days. After 15 days of incubation, eggs were
      transferred to hatching machine. Eggs were classified as thin-, medium-, and
      thick-shelled according to eggshell thickness values. RESULTS: Eggshell
      thicknesses were ranged between 0.24 and 0.36 mm, and the differences between the
      hatching rates of thickness values were not found significant. Hatchability of
      thin-, medium-, and thick-shelled eggs was found as 69.2%, 69.4%, and 82.4% for
      Experiment 1. These values were as 87.8%, 89.2%, and 91.9% for Experiment 2,
      respectively. Similar to eggshell thickness frequencies, the differences between
      hatching rates of eggshell thickness groups were found insignificant. CONCLUSION:
      Results of this study showed that eggshell thickness does not affect
      hatchability.

PMID- 29062203
TI  - Characterization and zoonotic impact of Shiga toxin producing Escherichia coli in
      some wild bird species.
AB  - AIM: Wild birds are considered silent vectors of some zoonotic water and food
      borne pathogens of public health significance. Owing to the importance of Shiga
      toxin producing Escherichia coli (STEC) as the most pathogenic among the emerging
      diarrheagenic E. coli groups that can infect man; the present study was designed
      to detect the occurrence of STEC among wild birds in Egypt. MATERIALS AND
      METHODS: A total of 177 intestinal content swab samples originating from five
      wild bird species were investigated for the presence of E. coli and STEC by
      standard culture methods. Suspect STEC isolates were further characterized by
      serotyping, random amplified polymorphic DNA polymerase chain reaction (RAPD
      PCR), antimicrobial resistance pattern and PCR detection of stx1, stx2, and eae
      genes. RESULTS: A total of 30 suspect STEC isolates from 30 positive birds'
      samples were detected and identified on STEC CHROMagar (semi-captive pigeons, 15;
      house crows, 8; cattle egrets, 3; moorhens, 2; and house teals, 2). 25 isolates
      were grouped into 13 serogroups (O:20, O:25, O:26, O:27, O:63, O:78, O:111,
      O:114, O:125, O:128, O:142, O:153, and O:158), while five were rough strains. The
      distribution of STEC virulence genes among wild birds was as follows: 16 birds
      carried stx1 gene only (nine pigeons [28.1%], six crows [7.1%], and one cattle
      egret [5.6%]). Stx1 and stx2 genes together were detected in four birds (one
      cattle egret [5.6%], two moorhens [6.1%], and one house teal, [10%]). Only one
      pigeon (3.1%) possessed the three alleles. Disk diffusion test results showed
      that cefixime was the most effective against STEC serotypes with (93.3%)
      sensitivity, followed by gentamycin (56.7%), and amoxicillin (50%). On the other
      hand, all the recovered STEC isolates were resistant to cefotaxime, doxycycline,
      cephalothin, and sulfisoxazole. RAPD fingerprinting using primers OPA-2 and OPA-9
      showed that STEC isolates were heterogeneous; they yielded 30 and 27 different
      clusters, respectively. CONCLUSIONS: Wild birds carry STEC and may add to the
      contamination of the surrounding environment.

PMID- 29062204
TI  - Repertoire of noncoding RNAs in corpus luteum of early pregnancy in buffalo
      (Bubalus bubalis).
AB  - AIM: The present study was designed to identify other noncoding RNAs (ncRNAs) in
      the corpus luteum (CL) during early pregnancy in buffalo. MATERIALS AND METHODS:
      For this study, CL (n=2) from two buffalo gravid uteri, obtained from the
      slaughter house, was transported to laboratory after snap freezing in liquid
      nitrogen (-196 degrees C). The stage of pregnancy was determined by measuring the
      crown-rump region of the fetus. This was followed by isolation of RNA and deep
      sequencing. Post-deep sequencing, the obtained reads were checked and aligned
      against various ncRNA databases (GtRNA, RFAM, and deep guide). Various
      parameters, namely, frequency of specific ncRNAs, length, mismatch, and genomic
      location target in several model species were deciphered. RESULTS: Frequency of
      piwi-interacting RNAs (piwi-RNAs), having target location in rodents and human
      genomes, were significantly higher compared to other piwi-RNAs and ncRNAs.
      Ribosomal RNAs (rRNAs) deduced had nucleotides (nts) ranging from 17 to 50 nts,
      but the occurrence of small length rRNAs was more than lengthier fragments. The
      target on 16S rRNA species confirms the conservation of 16S rRNA across species.
      With respect to transfer RNA (tRNA), the abundantly occurring tRNAs were unique
      with no duplication. Small nucleolar RNAs (snoRNAs), identified in this study,
      showed a strong tendency for coding box C/D snoRNAs in comparison to H/ACA
      snoRNAs. Regulatory and evolutionary implications of these identified ncRNAs are
      yet to be delineated in many species, including buffaloes. CONCLUSION: This is
      the first report of identification of other ncRNAs in CL of early pregnancy in
      buffalo.

PMID- 29062205
TI  - Epidemiological features and pathological study of avian leukosis in turkeys'
      flocks.
AB  - AIM: The purpose of this study was focused on the identification of tumor
      diseases in turkeys on the basis of a detailed description of epidemiological
      features, clinical signs, lesions, and histopathological changes. MATERIALS AND
      METHODS: Outbreak of a tumor disease in turkeys was investigated in various
      regions of Eastern Algeria. Four turkeys' flocks aged from 17 weeks were
      affected, resulting to mortality often over 10%, on a period of 15 days. The main
      epidemiological characters, clinical signs, and lesions were observed throughout
      all the course of the disease. Serum samples were collected from affected turkeys
      in each flock to detect p27 antigen in enzyme-linked immunosorbent assay (ELISA)
      test to diagnose avian leukosis virus (ALV). Portions of sciatic nerves and
      livers are taken from dead turkeys for microscopic examination. RESULTS: The
      disease was characterized by clinical signs such as anorexia, weakness, and
      diarrhea. Necropsy of the dead birds showed hepatomegaly and gross splenomegaly
      with neoplastic nodules or gray foci and diffuse infiltration in the myocardium
      and lungs. ALV antigen test using ELISA confirmed the presence of virus leukosis.
      Histopathological sections of the liver had proliferations of lymphoblastoid
      cells and absence of any modifications or lymphocytic infiltration in peripheral
      nerves. CONCLUSION: The present study confirms that this disease condition is
      caused by lymphoid leukosis.

PMID- 29062206
TI  - Prevalence of Corynosoma caspicum infection in Gasterosteus aculeatus fish in
      Caspian Sea, Northern Iran.
AB  - AIM: There is little information about the prevalence of Corynosoma caspicum in
      fish particularly Gasterosteus aculeatus in Iran and the world. The aim of the
      present study was to find out the prevalence of acanthocephalan infection in
      Babolsar district, southern coastal of Caspian Sea, Northern Iran. MATERIALS AND
      METHODS: Between September 2012 and August 2014, a total of 360 G. aculeatus
      fishes were randomly collected by drift nets from coastal regions in Babolsar and
      then examined the intestine and body cavity for worm infections. RESULTS: A total
      of 360 G. aculeatus fishes, 109 (30.3%) were found infected with at least one
      Corynosoma capsicum, and there was no significant association between genders and
      the prevalence infection of acanthocephalan. Moreover, there was a significant
      difference in infected rate between summer (79%, 86/109) and spring (21%, 23/109)
      (p<0.05). CONCLUSION: The high occurrence of Corynosoma infection in G. aculeatus
      indicates the enzootic constancy status of the infection in the southern coastal
      of Caspian Sea, Northern Iran.

PMID- 29062207
TI  - Congenital arthrogryposis-hydranencephaly syndrome caused by Akabane virus in
      newborn calves of Basrah Governorate, Iraq.
AB  - AIM: The study was conducted in Basrah, Iraq, to diagnose congenital
      arthrogryposis-hydranencephaly syndrome caused by Akabane virus (AKAV) in calves.
      MATERIALS AND METHODS: Affected animals (42 calves) are about 2-27 days old from
      both sexes show signs of arthrogryposis and hydranencephaly. Eight clinically
      healthy newborn calves were considered as controls. Diagnosis of AKAV was
      confirmed using a competition enzyme-linked immunosorbent assay test. RESULTS:
      Results show that all affected calves were found seropositive. Furthermore, a
      significant increase in total leukocyte count in diseased calves due to a
      significant increase in the absolute lymphocyte number indicated in affected
      calves than in controls. Moreover, a significant increase in sedimentation rate
      of erythrocytes was also encountered in diseased calves than in controls. In
      addition, a significant increase in haptoglobin level and fibrinogen was also
      detected. CONCLUSION: Diagnosis of AKAV infection of Basrah Governorate, Iraq,
      will provide useful epidemiological information for cattle and other domesticated
      animals. Therefore, abortion could be prevented and controlled.

PMID- 29062208
TI  - Impact of heat stress and hypercapnia on physiological, hematological, and
      behavioral profile of Tharparkar and Karan Fries heifers.
AB  - AIM: The present investigation was undertaken to study the impact of heat stress
      and hypercapnia on physiological, hematological, and behavioral profile of
      Tharparkar and Karan Fries (KF) heifers. MATERIALS AND METHODS: The animals of
      both the breeds of Tharparkar and KF were exposed at different temperatures and
      CO2 levels. Exposure conditions of 25 degrees C, 400 ppm CO2 level, and 60%
      relative humidity (RH) were taken as a control condition. The exposure conditions
      40 degrees C with two levels of CO2 500 ppm and 600 ppm with RH 55+/-5% and
      exposure conditions 42 degrees C with two levels of CO2 500 ppm and 600 ppm with
      RH 55+/-5% were taken as treatments. The exposure period in each condition was 4
      h daily for 5 consecutive days. RESULTS: Physiological responses (respiration
      rate [RR], pulse rate [PR], and rectal temperature [RT]) were significantly
      (p<0.01) higher and different during all exposure conditions compared to control
      condition in both the breeds of cattle. KF heifers had higher RR, PR, and RT than
      Tharparkar heifers. Hematological parameters, namely, red blood cell, hemoglobin,
      and packed cell volume were significantly higher and different during all
      exposure condition than control in both the breeds, whereas no significant
      changes were observed in total leukocyte count and differential leukocyte count.
      Blood pH increased with increase in temperature and CO2 levels and was
      significantly higher than control conditions. PCO2 and base excess were
      significantly (p<0.05) lower, and PO2 was higher during different exposure
      conditions than control in both breeds. Restlessness and excitement signs were
      observed in all the exposure conditions as compared to control condition in both
      the breeds. CONCLUSION: Changes in physiological responses, behavioral pattern,
      and hematological parameters reflect the current functional status of the body
      system, and it can be used as an index for assessing the adaptation capacity of
      cattle to predict changes occurring in climate variables due to increasing CO2
      levels and environmental temperature.

PMID- 29062209
TI  - The Maryland Orthopaedic Registry (MOR): Design and baseline characteristics of a
      prospective registry.
AB  - BACKGROUND: Utilization of patient-reported outcome tools allows a more accurate
      assessment of the efficacy of treatment, which is critical to comparative
      effectiveness research. OBJECTIVES: The Maryland Orthopaedic Registry (MOR) was
      established to assess post-surgical outcomes related to patients' pain,
      functional status, met expectations, and satisfaction using an electronic data
      collection system. Secondary aims of the registry include assessment of patient
      expectations of treatment, activity level, and general health status. METHODS:
      Adult patients enrolled in this prospective observational study completed self
      report measures assessing pre-operative pain, function, treatment expectations,
      and activity levels during the perioperative period. MOR utilizes the Patient
      Reported Outcomes Measurement Information System (PROMIS(r))'computer adaptive
      testing for physical function, pain interference, fatigue, social satisfaction,
      anxiety, and depression. Perioperative data is extracted from the medical record.
      RESULTS: 300 patients (40% of eligible) have been enrolled into the initial
      cohort. Most patients (94.1%) were aged 18-65, and 57% were male. Fifty-seven
      percent of enrollees were White, 33% Black, and 4% Asian. PROMIS physical
      function and social satisfaction were both more than half a standard deviation
      below the population mean. Participants reported PROMIS anxiety scores that were
      half a standard deviation above the population mean and pain interference scores
      that were more than a standard deviation above the mean. Physical function scores
      were significantly worse among participants with lower extremity orthopaedic
      issues, but scores on other measures were similar between participants undergoing
      lower or upper extremity surgery. CONCLUSIONS: MOR provides a comprehensive
      assessment of patients undergoing orthopaedic surgery. The utilization of
      electronic clinical assessment tools as well as computer adaptive testing allows
      for time-efficient data collection. The diverse population is a particular
      strength of MOR.

PMID- 29062210
TI  - Evaluation of outcome of proximal femur locking compression plate (PFLCP) in
      unstable proximal femur fractures.
AB  - INTRODUCTION: Pertrochanteric fractures are most frequent factures of the
      proximal femur, accounts for nearly 50% of all proximal femur fractures and are
      most devastating and also a major cause of disability in elderly. The aim and
      objective of this study was to evaluate the role of proximal femoral locking
      compression plate in unstable proximal femur fractures. MATERIAL AND METHOD: A
      total of 20 cases were included in our study (M:F - 16:4), who suffered proximal
      femur fracture due to various modalities and all of them were operated using
      proximal femoral locking compression plate. This proximal femoral fractures
      included unstable - intertrochanteric with subtrochanteric extension and
      subtrochanteric with intertrochanteric extensions as well as one case with
      intertrochanteric, subtrochanteric and neck of femur fracture. Patients were
      followed up regularly and minimum follow-up period was 12 months. Patients were
      given physiotherapy and partial weight bearing was started after 6 weeks
      postoperatively or after union was achieved. The outcome was evaluated as per
      Harris Hip Score and radiological union. RESULT: Among 20 cases with average age
      of 55.3 +/- 17.9 years, treated with PF-LCP, the average time of union 18.75 +/-
      3.67 weeks was achieved. We got 10 excellent, 3 good, 3 fair and 4 poor result
      with average Harris Hip Score of 80.2 +/- 28.54 with 65% good to excellent result
      with average Post-operative Neck Shaft Angle of 124.150 +/- 17.880 and with 45%
      rate of complication which included four cases of superficial infection and two
      cases of deep infection and late complications like four cases of non-union,
      deformity - three cases of coxa vara and 2 cases of coxa valga, with patients
      having more than one complication in them. CONCLUSION: PF-LCP is not recommended
      as a definitive implant but can be used as an alternative for the treatment of
      unstable proximal femoral fractures when there is no option available for other
      routinely used implants. Despite of its complications, PF-LCP is used where all
      implants fail.

PMID- 29062211
TI  - Outcomes of fracture shaft femur in pediatric population managed at emergency.
AB  - BACKGROUND: Fracture shaft of femur is amongst one of the commonest major
      diaphyseal injuries in school going children presenting to us at emergency rooms
      of our hospitals. The presence of a growing proximal and distal physes imposes a
      real challenge in management of these fractures. The use of titanium elastic
      nails has gained wide acceptance for stabilizing these fractures. MATERIALS AND
      METHODS: A sample of 53 children of age group 6 to 12 years were included in the
      study according to the inclusion and exclusion criteria. The mean age of subjects
      was 8.87 +/- 1.64 years of which 39 were males and 14 were females. The femoral
      shaft fractures were stabilized using titanium elastic nails and followed up for
      a mean duration of six months. The outcomes were evaluated based on Flynn's
      criteria. RESULTS: We obtained excellent outcome in 75.5% of our cases,
      satisfactory outcome in 17% and poor outcome in 7.5% of cases. We found no
      statistically significant difference in outcome in patients of age 9 years or
      less compared to 10 years or older. CONCLUSION: Patient selection is important to
      obtain good results using titanium elastic nails. Mid diaphyseal femoral shaft
      fractures with minimal comminution are ideal fractures for treatment using
      titanium elastic nails.

PMID- 29062212
TI  - Early reduction of acetabular fractures decreases the risk of post-traumatic hip
      osteoarthritis?
AB  - BACKGROUND: Acetabular fractures are complex high-energy injuries. Increasing in
      recent years with the increased use of high-speed motor vehicles. One of the most
      important complications of acetabular fracture is the post-traumatic hip
      osteoarthritis; this complication has been associated to poor fracture reduction,
      type of fracture and delay in the reduction and fixation of acetabular fracture
      (Timing surgery). The aims of this study were to determine the incidence of post
      traumatic hip osteoarthritis after acetabulum fracture and demonstrate whether
      the delay surgery is associated to early post-traumatic hip osteoarthritis.
      METHODS: Using the database of patients with acetabular fractures treated with
      open reduction and internal fixation (ORIF) over 3 years (2011-2014) with minimum
      of 2 years follow-up. Data was acquired and saved in a digital format.
      Demographic information was obtained from each patient with minimum of 2 years
      follow-up. Acetabular fracture was distributed according to the classification of
      Judet. The quality of reduction was classified in anatomic (0-1 mm) and non
      anatomic (>1 mm) and the timing surgery, early (<7 days) and delay (>7 days).
      Clinical and radiographic follow-up was generally performed at six weeks, three
      months, one and two years after fracture fixation. Multivariate logistic
      regression analyses were performed to assess the strength of the covariates in
      relation to the development of post-traumatic hip osteoarthritis. RESULTS: 59
      (48%) patients of 122, developed post-traumatic hip osteoarthritis before 2
      years. Posterior wall fracture with or without transverse fracture was associated
      with higher post-traumatic hip osteoarthritis compared with other types of
      fractures (p < 0.05). Patients with better anatomical reduction had less post
      traumatic hip osteoarthritis compared with those who had nonanatomic reduction (p
      < 0.05). There was no evidence of association between early timing of the
      surgical procedure and the presence post-traumatic hip osteoarthritis (p = 7092).
      CONCLUSIONS: According to our results, the anatomical reduction of the articular
      surface in acetabular fractures is the most important factor in hip
      osteoarthritis prevention. This factor is strongly associated with early surgical
      treatment, preferably done within seven days. The timing surgery it is not a
      factor associated with post-traumatic osteoarthritis.

PMID- 29062213
TI  - Antiglide versus lateral plate fixation for Danis-Weber type B malleolar
      fractures caused by supination-external rotation injury.
AB  - PURPOSE: The purpose of this study was to evaluate functional results and the
      frequency of complications in the distal fibula Danis-Weber type B fractures
      caused by supination-external rotation injury in a group of lateral and antiglide
      plate fixation. METHODS: This prospective study evaluated 44 patients with a
      minimum of one-year follow-up. Patients were divided into two groups: one lateral
      plate group (24 patients) and group with an antiglide plate (20 patients). The
      patients of both groups were always positioned supine, and lateral approach was
      used. In the lateral plate group, the fracture was anatomically reduced, an
      optional anteroposterior lag screw was placed perpendicular to fracture line, and
      then the one-third tubular plate was applied on the lateral fibular site. In the
      antiglide group, the palate was implemented on the posterolateral surface of the
      fibula and the fracture was anatomically reduced. An optional lag-screw was used.
      Distal screw fixation was applied deliberately. Functional assessment according
      to the American Orthopaedic Foot and Ankle Society hind foot-ankle score (AOFAS)
      were performed at one year after surgery. The complications were recorded.
      RESULTS: According to Lauge-Hansen classification of supination-external rotation
      injury, a total of 27 (61.4%) patients was classified as stage 2, 2 (4.5%)
      patients as stage 3 and 15 (34.1%) patients with stage 4. In the lateral plate
      group, there were 13 (54.2%) male and 11 (45.8%) female patients. In the
      antiglide plate group, men comprised 12 (60%) and women 8 (40%) of patients. The
      AOFAS in the lateral and antiglide group performed one year after surgery was, on
      average, 93.7 +/- 6.1 (range 85-100) and 94.5 +/- 6.0 (range 85-100) points
      respectively. There were no statistically significant differences in both groups
      (p = 0.37). Complications were observed in 7 (29.3%) patients of lateral plate
      and 3 (15%) patients of an antiglide plate (p = 0.31). There was no case of
      tendinopathy. Revision surgery was performed in one patient with superficial
      infection. CONCLUSION: In the present study, the outcome of the surgically
      treated Weber type B fractures caused by supination external rotation injury was
      comparable in both groups. The antiglide plate fixation showed no signs of
      peroneal tendinopathy, low rate of complications. We believe this technique is
      safe and a good method of fixation as well as traditional lateral plating.

PMID- 29062214
TI  - Analysis of the variables affecting outcome in fractures of the tibial pilon
      treated by open reduction and internal fixation.
AB  - OBJECTIVE: To assess variables that could be related to outcomes in fractures of
      the tibial pilon treated by open reduction and internal fixation (ORIF). DESIGN:
      Retrospective. SETTING: University Hospital. PATIENTS: A total 92 fractures of
      the tibial pilon treated by ORIF in a 5-year period. The minimum follow-up was 1
      year (mean: 3.3 years; range: 1-5). INTERVENTION: ORIF with LCP-LISS plate.
      PRIMARY OUTCOME MEASUREMENTS: Age, sex, side, type of fracture, energy of the
      injury, provisional external fixation (EF), time until ORIF, stages of treatment
      (one or two), surgical approach, type of bone fixation, quality of reduction,
      bone graft, hardware removal, associated fractures (fibula and others),
      functional results (AOFAS scale), rates of infection, skin necrosis, flap
      coverage, non-union, and early posttraumatic ankle osteoarthritis (AOA). RESULTS:
      According to AOFAS scale 30.5% of results were excellent, 46.7% good, 13.1% fair
      and 9.7% poor. Overall, the rate of infection was 13.04%, The rate of non-union
      was 10.86%. The rate of skin necrosis was 7.6% and the rate of flap coverage was
      13.04%. The rate of early posttraumatic AOA was 13.04%. Type 43C3 fractures of
      the AO classification had a higher rate of skin necrosis and flap coverage. Open
      fractures were related to a higher prevalence of nonunion and flap coverage. The
      use of a bone graft was associated with a higher rate of nonunion and poor
      results. Infection was related to a higher prevalence of fair and poor results.
      EF was associated with a higher need for flap coverage. A suboptimal anatomic
      reduction was related to a higher rate of fair and poor results. The anteromedial
      approach was associated with a higher prevalence of skin necrosis and early
      posttraumatic AOA than the anterolateral approach. The use of an medial plate was
      related to a higher rate of nonunion than the use of a lateral plate.
      CONCLUSIONS: The anteromedial approach was associated with a higher rate of skin
      necrosis and posttraumatic AOA than the anterolateral approach. Medial plating
      had a higher prevalence of nonunion than lateral plating. LEVEL OF EVIDENCE: IV
      (case series).

PMID- 29062215
TI  - Transverse pinning versus intramedullary pinning in fifth metacarpal's neck
      fractures: A randomized controlled study with patient-reported outcome.
AB  - INTRODUCTION: The 5th metacarpal fractures accounts for 38% of all hand fractures
      given that the neck is the weakest point in metacarpals, so neck fracture is the
      most common metacarpal fracture. Surgical fixation is also advocated for such
      fractures to prevent mal-rotation of the little finger which will lead to fingers
      overlap in a clenched fist. Various methods are available for fixation of such
      fractures, like intramedullary & transverse pinning. There are very few reports
      in the literature comparing both techniques. Authors wanted to compare outcomes
      and complications of transverse pinning versus intramedullary pinning in fifth
      metacarpal's neck fractures. METHODS: A single-center, parallel group,
      prospective, randomized study was conducted at an academic Level 1 Trauma Center
      from October 2014 to December 2016. A total of 80 patients with 5th metacarpal's
      neck fractures were randomized to pinning using either transverse pinning (group
      A) or intramedullary pinning (group B). Patients were assessed clinically on
      range of motion, patient-reported outcome using the Quick-DASH (Disabilities of
      the Arm, Shoulder, and Hand) questionnaire & radiographically. Two blinded
      observers assessed outcomes. RESULTS: At final follow up for each patient (12
      months) the statistically significant differences were observed in operative
      time, the transverse pinning group showed shorter operative time, as well as
      complication rate as complications were observed only in intramedullary pinning
      group. No differences were found in range of motion or the Quick-DASH score.
      CONCLUSION: Both techniques are equally safe and effective treatment option for
      5th metacarpal's neck fractures. The only difference was shorter operative time &
      less incidence of complications in transverse pinning group. LEVEL OF EVIDENCE:
      Level II, Therapeutic study.

PMID- 29062216
TI  - Impending gangrene of fingers by constriction bands of mother's hair mistaken as
      pernio by parents: A case series of 10 infants.
AB  - BACKGROUND: Long harsh winter in Kashmir Valley increase the incidence of pernio
      in children so much that common people consider every hand swelling as pernio.
      METHODS: 10 Infants over two years were brought to our hospital as cases of
      pernio involving fingers. RESULTS: All the infants came out to be cases of
      impending gangrene due to mother's hair as constriction bands around fingers.
      CONCLUSION: Impending gangrene of fingers in infants due to mother hair as
      constriction band is very rare. However its symptoms overlap with symptoms of
      peripheral cold injuries and can be easily mistaken for each other by people.

PMID- 29062217
TI  - Introduction to "tension loop internal fixation" of simple fractures and
      "Faisal's double noose loops".
AB  - In this paper, is described a new method of internal fixation for smaller bone
      fractures without comminution and with interdigitating ends, especially clavicle
      and forearm bones. Fixation and compression are achieved by a new technique
      called "the double noose loop". This fixation can be Temporary to allow placement
      of a plate easily. Or it can also be used as a Definitive fixation along with a
      splint. Faisal's double noose loop is a suture passed through bone and over
      fracture, with noose knots at both ends that are linked to form a loop around
      fracture. The loop can be tightened to decrease the circumference/diameter of the
      loop by a big amount, thus allowing compression.

PMID- 29062218
TI  - Pediatric conjoint Hoffa's fracture: An uncommon injury and review of literature.
AB  - Coronal plane fracture of femoral condyles was first elaborated by Hoffa. These
      are difficult articular injuries, often described in adult skeleton and very
      rarely in pediatric age group. Conjoint variety with intact bone bridge between
      condyles in intercondylar notch area is rare. We report a conjoint variety of
      bicondylar Hoffa's fracture in a child which was surgically treated using
      headless compression screws along with a brief review of literature about
      fracture entity and complexities associated with it.

PMID- 29062219
TI  - Stories that move them: Changing children's behaviour toward diverse peers.
AB  - Globally, our social worlds are becoming increasingly racially and ethnically
      diverse. Despite this, little attention has been given to how children negotiate
      this diversity. In this study we examine whether a value-in-diversity storybook
      intervention encourages young children to engage in intergroup contact with
      racially diverse peers. The lunchroom seating behaviour of 4- to 6-year-olds
      attending three racially diverse primary schools was recorded at three different
      points during a one-week period. Seating behaviour was coded based on the race of
      the children and levels of segregation were calculated (Campbell et al., 1996).
      Before hearing the story, we observed racial self-segregation; children were more
      likely to sit with same-race peers. However, immediately following the story,
      children were no longer significantly racially segregated. This effect was not
      maintained; up to 48 hours later children again showed evidence of racial self
      segregation. Our findings suggest that exposure to racially diverse peers alone
      is not sufficient for promoting intergroup contact. We argue that it is vital to
      develop sustainable teacher-led interventions if we are to harness the potential
      of diverse school settings for bolstering intergroup relations.

PMID- 29062220
TI  - Development and Refinement of a Targeted Sexual Risk Reduction Intervention for
      Women With a History of Childhood Sexual Abuse.
AB  - Childhood sexual abuse (CSA) is associated with sexual risk behavior in
      adulthood. Traditional sexual risk reduction interventions do not meet the unique
      needs of women who have been sexually abused. In the current paper, we describe
      the four-stage process we followed to develop and refine a targeted sexual risk
      reduction intervention for this population. First, initial quantitative work
      revealed that the intervention should address how maladaptive thoughts related to
      traumatic sexualization, trust, powerlessness, and guilt/shame (traumagenic
      dynamics constructs) influence current sexual behavior. Second, qualitative
      interviews with 10 women who reported a history of CSA (M age = 34 years; 90%
      African American) as well as current sexual risk behavior provided support for
      targeting maladaptive thoughts associated with these traumagenic dynamics
      constructs. Third, based on the qualitative and quantitative results, we
      developed a 5-session, group-delivered intervention to address the maladaptive
      thoughts that occurred as a result of CSA, as well as the cognitive-behavioral
      determinants of sexual risk behavior. This intervention drew heavily on cognitive
      behavioral techniques to address cognitions associated with CSA and the links
      between these cognitions and current sexual risk behavior. Techniques from trauma
      based therapies, as well as motivational techniques, were also incorporated into
      the intervention. Finally, we refined the intervention with 24 women (M age = 33
      years; 79% African American), and assessed feasibility and acceptability. These
      women reported high levels of satisfaction with the intervention. The resultant
      intervention is currently being evaluated in a small, randomized controlled
      trial.

PMID- 29062221
TI  - The importance of genetic testing as demonstrated by two cases of CACNA1F
      associated retinal generation misdiagnosed as LCA.
AB  - PURPOSE: To describe in detail cases with an initial diagnosis of Leber
      congenital amaurosis that were later found to have a hemizygous mutation in the
      CACNA1F gene. METHODS: The patients underwent a detailed ophthalmological
      evaluation and full-field electroretinography (ERG). Selective targeted capture
      and whole-exome next-generation sequencing (NGS) were used to find the disease
      causing mutations. RESULTS: Patient 1 presented at age 3 months with nystagmus,
      normal visual attention, and a normal fundus exam. ERG responses were severely
      decreased. Patient 2 presented with nystagmus, severe hyperopia, esotropia, and
      visual acuity of 20/360 oculus dexter (OD) and 20/270 oculus sinister (OS) at age
      5 months. His fundus exam showed slightly increased pigmentation around the
      foveae. The scotopic ERG responses were severely decreased and photopic responses
      mildly decreased. Based on the initial presentation, both patients received the
      clinical diagnosis of Leber congenital amaurosis (LCA). However, genetic testing
      showed no mutations in known LCA genes. Instead, broader genetic testing using
      NGS showed point mutations in the CACNA1F gene, which is reported to be
      associated with type 2 congenital stationary night blindness (CSNB2).
      CONCLUSIONS: These two cases demonstrate the clinical overlap between LCA and
      CSNB in infants and young children. Genetic testing is an essential tool in these
      cases and provides a more accurate diagnosis and prognosis for patients with
      inherited retinal degenerative disorders.

PMID- 29062222
TI  - Retinal gene expression responses to aging are sexually divergent.
AB  - PURPOSE: Sex and age are critical factors in a variety of retinal diseases but
      have garnered little attention in preclinical models. The current lack of
      knowledge impairs informed decision making regarding inclusion and design of
      studies that incorporate both sexes and/or the effects of aging. The goal of this
      study was to examine normative mouse retina gene expression in both sexes and
      with advancing age. METHODS: Retinal gene expression in female and male C57BL/6JN
      mice at 3 months and 24 months of age were compared for sex differences and aging
      responses through whole transcriptome microarray analysis. Sex differences and
      age-related changes were examined in the context of cellular pathways and
      processes, regulatory patterns, and cellular origin, as well as for overlap with
      described changes in retinal disease models. Selected age and sex differences
      were confirmed with quantitative PCR. RESULTS: Age-related gene expression
      changes demonstrated commonalities and sexually divergent responses. Several
      cellular pathways and processes, especially inflammation-related, are affected
      and were over-represented in fibroblast, microglial, and ganglion cell-specific
      genes. Lifelong, and age-dependent, sex differences were observed and were over
      represented in fibroblast-specific genes. Age and sex differences were also
      observed to be regulated in models of diabetic retinopathy, glaucoma, and other
      diseases. CONCLUSIONS: These findings demonstrate that most age-related changes
      in retinal gene expression are sexually divergent and that there are significant
      sex differences in gene expression throughout the lifespan. These data serve as a
      resource for vision researchers seeking to include sex and age as factors in
      their preclinical studies.

PMID- 29062223
TI  - Enhancing the efficacy of AREDS antioxidants in light-induced retinal
      degeneration.
AB  - PURPOSE: Light-induced photoreceptor cell degeneration and disease progression in
      age-related macular degeneration (AMD) involve oxidative stress and visual cell
      loss, which can be prevented, or slowed, by antioxidants. Our goal was to test
      the protective efficacy of a traditional Age-related Eye Disease Study
      antioxidant formulation (AREDS) and AREDS combined with non-traditional
      antioxidants in a preclinical animal model of photooxidative retinal damage.
      METHODS: Male Sprague-Dawley rats were reared in a low-intensity (20 lux) or high
      intensity (200 lux) cyclic light environment for 6 weeks. Some animals received a
      daily dietary supplement consisting of a small cracker infused with an AREDS
      antioxidant mineral mixture, AREDS antioxidants minus zinc, or zinc oxide alone.
      Other rats received AREDS combined with a detergent extract of the common herb
      rosemary, AREDS plus carnosic acid, zinc oxide plus rosemary, or rosemary alone.
      Antioxidant efficacy was determined by measuring retinal DNA levels 2 weeks after
      6 h of intense exposure to white light (9,000 lux). Western blotting was used to
      determine visual cell opsin and arrestin levels following intense light
      treatment. Rhodopsin regeneration was determined after 1 h of exposure to light.
      Gene array analysis was used to determine changes in the expression of retinal
      genes resulting from light rearing environment or from antioxidant
      supplementation. RESULTS: Chronic high-intensity cyclic light rearing resulted in
      lower levels of rod and cone opsins, retinal S-antigen (S-ag), and medium
      wavelength cone arrestin (mCAR) than found for rats maintained in low cyclic
      light. However, as determined by retinal DNA, and by residual opsin and arrestin
      levels, 2 weeks after acute photooxidative damage, visual cell loss was greater
      in rats reared in low cyclic light. Retinal damage decreased with AREDS plus
      rosemary, or with zinc oxide plus rosemary whereas AREDS alone and zinc oxide
      alone (at their daily recommended levels) were both ineffective. One week of
      supplemental AREDS plus carnosic acid resulted in higher levels of rod and cone
      cell proteins, and higher levels of retinal DNA than for AREDS alone. Rhodopsin
      regeneration was unaffected by the rosemary treatment. Retinal gene array
      analysis showed reduced expression of medium- wavelength opsin 1 and arrestin C
      in the high-light reared rats versus the low-light rats. The transition of rats
      from low cyclic light to a high cyclic light environment resulted in the
      differential expression of 280 gene markers, enriched for genes related to
      inflammation, apoptosis, cytokine, innate immune response, and receptors.
      Rosemary, zinc oxide plus rosemary, and AREDS plus rosemary suppressed 131, 241,
      and 266 of these genes (respectively) in high-light versus low-light animals and
      induced a small subset of changes in gene expression that were independent of
      light rearing conditions. CONCLUSIONS: Long-term environmental light intensity is
      a major determinant of retinal gene and protein expression, and of visual cell
      survival following acute photooxidative insult. Rats preconditioned by high-light
      rearing exhibit lower levels of cone opsin mRNA and protein, and lower mCAR
      protein, than low-light reared animals, but greater retention of retinal DNA and
      proteins following photooxidative damage. Rosemary enhanced the protective
      efficacy of AREDS and led to the greatest effect on the retinal genome in animals
      reared in high environmental light. Chronic administration of rosemary
      antioxidants may be a useful adjunct to the therapeutic benefit of AREDS in
      slowing disease progression in AMD.

PMID- 29062224
TI  - Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome:
      clinical perspectives.
AB  - Idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome
      typically affects young, healthy individuals. Despite the dramatic fundus
      appearance seen in this syndrome, these patients are usually asymptomatic. The
      syndrome includes peculiar vascular abnormalities in the form of multiple
      aneurysmal dilatations seen along retinal arterioles and optic nerve-head
      arterioles, which are best appreciated on fluorescein angiography. Neuroretinitis
      and retinal vasculitis are seen in all patients, and manifested by staining of
      the optic nerve head and diffuse leakage from vessels, mainly arterioles, on
      fluorescein angiography. The devastating vision-threatening outcomes of this
      syndrome include exudative retinopathy and extensive peripheral retinal
      nonperfusion areas, which can eventually lead to neovascularization. This review
      summarizes current knowledge on the variable clinical aspects of this disease,
      highlighting diagnostic and treatment strategies.

PMID- 29062226
TI  - The effect of Polygonum minus extract on cognitive and psychosocial parameters
      according to mood status among middle-aged women: a randomized, double-blind,
      placebo-controlled study [Retraction].
AB  - [This retracts the article on p. 1505 in vol. 10, PMID: 26445532.].

PMID- 29062225
TI  - Short vs prolonged dual antiplatelet treatment upon endovascular stenting of
      peripheral arteries.
AB  - INTRODUCTION: Peripheral artery disease (PAD) is a highly prevalent disorder with
      a substantial economical burden. Dual antiplatelet treatment (DAPT) upon
      endovascular stenting to prevent acute thrombotic reocclusions is an universally
      accepted practice for postinterventional management of PAD patients. However, the
      optimal period of time for DAPT upon endovascular stenting is not known. METHODS:
      In the current nonrandomized, retrospective monocentric study, we evaluated the
      duration of DAPT upon endovascular stenting. A total of 261 endovascular SFA and
      iliac stenting procedures were performed on 214 patients and these patients were
      subdivided into a short (4-6 weeks) or a prolonged (8-12 weeks) DAPT regime
      group. More than 65% of the patients included were male, approximately 35% were
      diabetic, and 61% had a history of smoking. Of all the patients, 90% exhibited a
      Rutherford stage 2-3, and approximately half of the patients had a moderate-to
      severe calcified target lesion with a length of >13 cm. Major safety end points
      were defined as any bleeding, compartment syndrome, and ischemic events. In
      addition to this, patency, all-cause mortality, as well as amputation were
      followed up over a period of 12 months upon intervention. RESULTS: Twelve months
      after endovascular stenting, primary patency in our cohort was comparable between
      the groups (83.94% short vs 79.8% long DAPT, P>0.05). Major bleeding occurred in
      18 cases without any difference between the groups (P>0.05). In addition, during
      the 12-month follow-up, 6 (3.4%) patients in the short and 3 (3.5%) in the
      prolonged DAPT regime suffered a stroke/transient ischemic attack (P>0.05). In
      addition, there was no difference regarding mortality and amputation rate
      comparing short vs prolonged DAPT regime in a 12-month follow-up. CONCLUSION: In
      the current cohort, prolonged DAPT after endovascular stenting had no beneficial
      effect on the outcome in a 12-month follow-up.

PMID- 29062227
TI  - Spectrum of noncerebrovascular rapidly progressive cognitive deterioration: a 2
      year retrospective study.
AB  - PURPOSE: The number of cognitive deterioration patients has been steadily
      increasing as the population ages in China. Patients with cognitive deterioration
      demonstrated diverse patterns, often making the diagnosis difficult, especially
      in rapidly progressive cognitive deterioration (RPCD) patients. The purpose of
      this study was to exhibit the disease spectrum and frequency of
      noncerebrovascular RPCD in patients from a medical college hospital of
      southeastern China. MATERIALS AND METHODS: We performed a 2-year retrospective
      cohort study including 310 RPCD patients who had been admitted to the Department
      of Neurology, Second Affiliated Hospital, Zhejiang University School of Medicine,
      from January 1, 2015 to December 31, 2016. RPCD patients' information on
      epidemiologic data and clinical aspects were collected. All the data were
      analyzed using SPSS. RESULTS: Of a total of 310 patients hospitalized for RPCD
      diagnosis, mean age of onset was 55.92+/-18.89 years. The most common cause of
      RPCD was viral encephalitis, accounting for 21.9% (68) of the cases, followed by
      Alzheimer's disease and autoimmune encephalitis, accounting for 14.5% (45) and
      9.0% (28) of the cases, respectively. Creutzfeldt-Jakob disease accounted for
      7.1% (22) of the cases. Patients in the secondary RPCD group tended to be younger
      than those in the primary RPCD group and experienced a more rapid progression
      course. CONCLUSION: Our study suggests that the most common causes of RPCD are
      secondary neurological diseases and most of them are potentially reversible under
      appropriate treatment of the underlying disease. The spectrum and frequency of
      RPCD in our cohort is comparable with a previous study performed in the European
      population.

PMID- 29062229
TI  - Triple therapy in COPD: new evidence with the extrafine fixed combination of
      beclomethasone dipropionate, formoterol fumarate, and glycopyrronium bromide.
AB  - The goals of COPD therapy are to prevent and control symptoms, reduce the
      frequency and severity of exacerbations, and improve exercise tolerance. The
      triple combination therapy of inhaled corticosteroids (ICSs), long-acting beta2
      agonists (LABAs), and long-acting muscarinic antagonists (LAMAs) has become an
      option for maintenance treatment of COPD and as a "step-up" therapy from single
      or double combination treatments. There is evidence that triple combination
      ICS/LABA/LAMA with different inhalers improves lung function, symptoms, and
      health status and reduces exacerbations. A new triple fixed-dose combination of
      extrafine beclomethasone dipropionate (100 ug/puff)/formoterol fumarate (6
      ug/puff)/glycopyrronium bromide (12.5 ug/puff) has been developed as a
      hydrofluoroalkane pressurized metered dose inhaler. Two large pivotal studies
      showed that this extrafine fixed ICS/LABA/LAMA triple combination is superior to
      fixed ICS/LABA combined therapy and also superior to the LAMA tiotropium in terms
      of lung function and exacerbation prevention in COPD patients at risk of
      exacerbation. This review considers the new information provided by these
      clinical trials of extrafine triple therapy and the implications for the clinical
      management of COPD patients.

PMID- 29062228
TI  - Impact and prevention of severe exacerbations of COPD: a review of the evidence.
AB  - Severe exacerbations of COPD, ie, those leading to hospitalization, have profound
      clinical implications for patients and significant economic consequences for
      society. The prevalence and burden of severe COPD exacerbations remain high,
      despite recognition of the importance of exacerbation prevention and the
      availability of new treatment options. Severe COPD exacerbations are associated
      with high mortality, have negative impact on quality of life, are linked to
      cardiovascular complications, and are a significant burden on the health-care
      system. This review identified risk factors that contribute to the development of
      severe exacerbations, treatment options (bronchodilators, antibiotics,
      corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe
      exacerbations, and strategies to prevent readmission to hospital. Risk factors
      that are amenable to change have been highlighted. A number of bronchodilators
      have demonstrated successful reduction in risk of severe exacerbations, including
      long-acting muscarinic antagonist or long-acting beta2-agonist mono- or
      combination therapies, in addition to vaccination, mucolytic and antibiotic
      therapy, and nonpharmacological interventions, such as pulmonary rehabilitation.
      Recognition of the importance of severe exacerbations is an essential step in
      improving outcomes for patients with COPD. Evidence-based approaches to prevent
      and manage severe exacerbations should be implemented as part of targeted
      strategies for disease management.

PMID- 29062231
TI  - Positive end-expiratory pressure attenuates hemodynamic effects induced by an
      overload of inspiratory muscles in patients with COPD.
AB  - BACKGROUND: Inspiratory muscle training (IMT) using a Threshold(r) device is
      commonly used to improve the strength and endurance of inspiratory muscles.
      However, the effect of IMT, alone or with positive end-expiratory pressure
      (PEEP), on hemodynamic parameters in patients with chronic obstructive pulmonary
      disease (COPD) remains unknown. OBJECTIVE: To assess the effects of an overload
      of inspiratory muscles using IMT fixed at 30% of the maximal inspiratory pressure
      (MIP), and IMT associated with 5 cmH2O of PEEP (IMT + PEEP), on the
      echocardiographic parameters in healthy subjects and patients with COPD. METHODS:
      Twenty patients with COPD (forced expiratory volume in 1 second 53.19+/-24.71
      pred%) and 15 age-matched healthy volunteers were evaluated using spirometry,
      MIP, the COPD assessment test (CAT), and the modified Medical Research Council
      (mMRC) dyspnea scale. The E- (fast-filling phase) and A- (atrial contraction
      phase) waves were evaluated at the tricuspid and mitral valves during inspiration
      and expiration in the following sequence: at basal conditions, using IMT, and
      using IMT + PEEP. RESULTS: Patients with COPD had reduced MIPs versus the control
      group. Ten patients had CAT scores <10 and 12 patients had mMRC scores <2. E-wave
      values at the mitral valve were significantly decreased with IMT during the
      inspiratory phase in both groups. These effects were normalized with IMT + PEEP.
      During the expiratory phase, use of IMT + PEEP normalized the reduction in E-wave
      values in the COPD group. During inspiration at the tricuspid valve, reduction in
      E-wave values during IMT was normalized by IMT + PEEP in COPD group. During the
      expiratory phase, the value of the E-waves was significantly reduced with
      overload of the inspiratory muscles in both groups, and these effects were
      normalized with IMT + PEEP. A-waves did not change under any conditions.
      CONCLUSION: Acute hemodynamic effects induced by overloading of the inspiratory
      muscles were attenuated and/or reversed by the addition of PEEP in COPD patients.

PMID- 29062230
TI  - Treatment burden, clinical outcomes, and comorbidities in COPD: an examination of
      the utility of medication regimen complexity index in COPD.
AB  - BACKGROUND: COPD patients are often prescribed multiple medications for their
      respiratory disease and comorbidities. This can lead to complex medication
      regimens resulting in poor adherence, medication errors, and drug-drug
      interactions. The relationship between clinical outcomes and medication burden
      beyond medication count in COPD is largely unknown. OBJECTIVES: The aim of this
      study was to explore the relationships of medication burden in COPD with clinical
      outcomes, comorbidities, and multidimensional indices. METHODS: In a cross
      sectional study, COPD patients (n=222) were assessed for demographic information,
      comorbidities, medication use, and clinical outcomes. Complexity of medication
      regimens was quantified using the validated medication regimen complexity index
      (MRCI). RESULTS: Participants (58.6% males) had a mean (SD) age of 69.1 (8.3)
      years with a postbronchodilator forced expiratory volume in 1 second % predicted
      of 56.5 (20.4) and a median of five comorbidities. The median (q1, q3) total MRCI
      score was 24 (18.5, 31). COPD-specific medication regimens were more complex than
      those of non-COPD medications (median MRCI: 14.5 versus 9, respectively;
      P<0.0001). Complex dosage formulations contributed the most to higher MRCI scores
      of COPD-specific medications while dosing frequency primarily drove the
      complexity associated with non-COPD medications. Participants in Global
      Initiative for Chronic Obstructive Lung Disease quadrant D had the highest median
      MRCI score for COPD medications (15.5) compared to those in quadrants A (13.5;
      P=0.0001) and B (12.5; P<0.0001). Increased complexity of COPD-specific
      treatments showed significant but weak correlations with lower lung function and
      6-minute walk distance, higher St George's Respiratory Questionnaire and COPD
      assessment test scores, and higher number of prior year COPD exacerbations and
      hospitalizations. Comorbid cardiovascular, gastrointestinal, or metabolic
      diseases individually contributed to higher total MRCI scores and/or medication
      counts for all medications. Charlson Comorbidity Index and COPD-specific
      comorbidity test showed the highest degree of correlation with total MRCI score
      (rho=0.289 and rho=0.326; P<0.0001, respectively). CONCLUSION: In COPD patients,
      complex medication regimens are associated with disease severity and specific
      class of comorbidities.

PMID- 29062233
TI  - Sporadic hyperekplexia due to self-limiting brainstem encephalopathy.
AB  - Hyperekplexia is a rare movement disorder characterized by pathologically
      exaggerated response to unexpected stimuli. It is differentiated from the normal
      startle reflex by its lower threshold, higher intensity, and resistance to
      habituation. Many of the acquired hyperekplexias result from brainstem
      involvement such as encephalitis, infarct, hemorrhage, pontocerebellar hypoplasia
      and medullary compression. This case report depicts a rare manifestation of
      hyperekplexia. The unusual aspect of this case was the vocalization that was
      reproduced in response to startling stimuli. Startle induced vocalization is not
      a part of the classical hyperekplexia description. When faced with a patient with
      pathologically exaggerated response to unexpected stimuli, the physician should
      consider this rare condition in the differential diagnosis, and also keep in mind
      that the disease may present with features different from those listed in the
      textbooks.

PMID- 29062232
TI  - Mitochondrial multiorgan disorder syndrome score generated from definite
      mitochondrial disorders.
AB  - OBJECTIVES: Mitochondrial disorders (MIDs) frequently present as mitochondrial
      multiorgan disorder syndrome (MIMODS) at onset or evolve into MIMODS during the
      course. This study aimed to find which organs and/or tissues are most frequently
      affected by MIMODS, which are the most frequent abnormalities within an affected
      organ, whether there are typical MIMODS patterns, and to generate an MIMODS score
      to assess the diagnostic probability for an MID. METHODS: This is a retrospective
      evaluation of clinical, biochemical, and genetic investigations of adult patients
      with definite MIDs. A total of 36 definite MID patients, 19 men and 17 women,
      aged 29-82 years were included in this study. The diagnosis was based on genetic
      testing (n=21), on biochemical investigations (n=17), or on both (n=2). RESULTS:
      The number of organs most frequently affected was 4 ranging from 1 to 9. MIMODS
      was diagnosed in 97% of patients. The organs most frequently affected were the
      muscle (97%), central nervous system (CNS; 72%), endocrine glands (69%), heart
      (58%), intestines (55%), and peripheral nerves (50%). The most frequent CNS
      abnormalities were leukoencephalopathy, prolonged visually evoked potentials, and
      atrophy. The most frequent endocrine abnormalities included thyroid dysfunction,
      short stature, and diabetes. The most frequent cardiac abnormalities included
      arrhythmias, systolic dysfunction, and hypertrophic cardiomyopathy. The most
      frequent MIMODS patterns were encephalomyopathy, encephalo-myo-endocrinopathy,
      and encepalo-myo-endocrino-cardiopathy. The mean +/- 2SD MIMODS score was 35.97+/
      27.6 (range =11-71). An MIMODS score >10 was regarded as indicative of an MID.
      CONCLUSION: Adult MIDs manifest as MIMODS in the vast majority of the cases. The
      organs most frequently affected in MIMODS are muscles, CNS, endocrine glands, and
      heart. An MIMODS score >10 suggests an MID.

PMID- 29062234
TI  - Serum bone alkaline phosphatase is a useful marker to evaluate lumbar bone
      mineral density in Japanese postmenopausal osteoporotic women during denosumab
      treatment.
AB  - A worldwide health concern, osteoporosis (OP), increases the risk of bone
      fracture and results in morbidity. This study examined whether the representative
      bone absorption marker serum tartrate-resistant acid phosphatase 5b (TRACP-5b) or
      bone formation marker bone alkaline phosphatase (BAP) could estimate primary OP
      status and denosumab efficacy in a real-world setting. We retrospectively
      enrolled 114 female postmenopausal primary OP patients in Japan. Values and
      percent changes in TRACP-5b, BAP, lumbar 1-4 bone mineral density (L-BMD), and
      total hip BMD (H-BMD) were assessed before treatment and at 4, 8, and 12 months
      of therapy to identify the correlations between the percent changes in bone
      metabolic markers and BMD. We also established two sets of subgroups based on the
      upper limits of reference values in Japan for serum: TRACP-5b (<420 mU/dL) and
      (>=420 mU/dL) and BAP (<14.5 ug/L) and (>=14.5 ug/L). Negative correlations were
      observed for the percent changes of TRACP-5b and H-BMD at 4 months (r=-0.3476)
      and 8 months (r=-0.3880), for the percent changes of BAP and H-BMD at 8 months
      (r=-0.3354), and for the percent changes of BAP and L-BMD at 12 months (r=
      0.3186). We observed a significant difference between the subgroups for the
      percent changes of L-BMD at 8 months (p=0.013) and 12 months (p=0.004) in BAP
      values. These results suggest that TRACP-5b and BAP had negative correlations
      with BMD, and that BAP represented a useful serum marker to evaluate L-BMD during
      denosumab therapy for OP.

PMID- 29062235
TI  - Real-world experience of everolimus as second-line treatment in metastatic renal
      cell cancer after failure of pazopanib.
AB  - AIM: We aimed to provide real-life data on the outcomes of metastatic renal cell
      carcinoma (mRCC) patients treated with everolimus as second-line treatment after
      failure of first-line pazopanib. PATIENTS AND METHODS: Data from the medical
      charts of mRCC patients from 8 centers in Greece and Spain were reviewed. All
      patients had received or were continuing to receive second-line everolimus
      treatment after failure of first-line treatment with pazopanib. No other previous
      therapies were allowed. The primary end point was the determination of
      progression-free survival (PFS). RESULTS: In total, 31 patients were enrolled. Of
      these, 26% had performance status (PS) >0, 88% were of intermediate/poor Memorial
      Sloan-Kettering Cancer Center (MSKCC) risk group, and only 61% had undergone
      prior nephrectomy. Median PFS was 3.48 months (95% CI: 2.37-5.06 months). Median
      overall survival (OS) from everolimus initiation was 8.9 months (95% CI: 6.47
      13.14 months). Median OS from pazopanib initiation was 14.78 months (95% CI:
      10.54-19.08 months). Furthermore, 32% of patients temporarily discontinued
      everolimus due to adverse events (AEs), and 22% of patients discontinued
      everolimus permanently due to toxicity. Most common toxicities were anemia (29%),
      stomatitis (26%), pneumonitis (19%), and fatigue (10%). Moreover, 14 AEs (27%)
      were graded as 3 or 4 and were reported by 13 patients (42%). CONCLUSION: This
      study provides data exclusively on the sequence pazopanib-everolimus in mRCC.
      Everolimus has a favorable safety profile and is active. The short PFS and OS
      could be attributed to the fact that the pazopanib-everolimus sequence was mainly
      offered to patients with adverse prognostic features, resulting in a modest
      increase in the combined OS of our population.

PMID- 29062236
TI  - NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a
      5p/BCL2.
AB  - BACKGROUND: Nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated
      to act as a tumor inhibitor in many cancers. However, the role of NEAT1 in the
      development of ovarian cancer (OC) remains far from being elaborated. Hence, the
      aim of this study is to investigate the expression and function of NEAT1 in OC.
      MATERIALS AND METHODS: The expression level of NEAT1 was determined by
      quantitative real-time polymerase chain reaction in OC cell lines. MTT assay,
      caspase-3 activity assay, and flow cytometry analysis were conducted to
      investigate the effects of NEAT1, miR-34a-5p, or B-cell lymphoma-2 (BCL2) on OC
      cell proliferation and apoptosis. Luciferase reporter assay was used to confirm
      the interaction of NEAT1, BCL2, and miR-34a-5p in OC cells. RESULTS: NEAT1 was
      significantly upregulated in OC cell lines. NEAT1 overexpression promoted
      proliferation by increasing the proportion of cells in S phase and suppressed
      apoptosis of OC cells, while knockdown of NEAT1 had the opposite effect. In
      addition, NEAT1 was demonstrated to directly interact with miR-34a-5p and exert
      its oncogenic role in OC by negatively regulating miR-34a-5p. Moreover, miR-34a
      5p could directly target BCL2 and suppressed its expression. miR-34a-5p
      overexpression suppressed OC cell proliferation and triggered apoptosis by
      targeting BCL2. Furthermore, NEAT1 knockdown suppressed BCL2 expression, while
      anti-miR-34a-5p dramatically abated the inhibitory effect of si-NEAT1 on BCL2
      expression. CONCLUSION: NEAT1 regulated proliferation and apoptosis of OC cells
      by miR-34a-5p/BCL2, providing a potential therapeutic approach for the treatment
      of OC patients.

PMID- 29062237
TI  - Low platelet count is potentially the most important contributor to severe
      bleeding in patients newly diagnosed with acute promyelocytic leukemia.
AB  - The objective of the current study was to provide more appropriate therapeutic
      strategies for reducing severe hemorrhaging by assessing the recovery of abnormal
      coagulation indexes in patients with acute promyelocytic leukemia (APL) during
      induction therapy. Retrospective analyses of 112 patients newly diagnosed with
      APL were performed during initial treatment. In our study, the early death rate
      was 5.36%. Hemorrhage was the leading cause of death during the induction period
      (4/6). The values of white blood cell count, lactate dehydrogenase, prothrombin
      time (PT), fibrinogen (Fbg), hemoglobin, and bone marrow leukemic promyelocytes
      were significantly different in the high-risk group compared to the
      low/intermediate-risk groups. There were significant differences in the white
      blood cell count, bone marrow leukemic promyelocytes, platelet (PLT) count, and
      the levels of lactate dehydrogenase, d-dimer, PT, and Fbg, as well as in FLT3-ITD
      mutations between patients with major bleeding and those with minor bleeding.
      Hemostatic variables significantly improved over time during induction therapy.
      The recovery times of the PLT, PT, and Fbg values were significantly slower in
      patients with major bleeding than in those with minor bleeding. Specifically, the
      PLT level in patients with major bleeding was not similar to that in the minor
      bleeding group until after 4 weeks of treatment. Hemorrhages were the most common
      cause of induction death in this study. High-risk patients were more prone to
      serious clinical bleeding symptoms. Patients with major bleeding had more rapid
      proliferation characteristics and an increased incidence of FLT3-ITD mutations
      compared to patients with minor bleeding. Hemostatic variables recovered
      significantly more slowly in patients with major bleeding than in those with
      minor bleeding. Active induction therapy and blood product infusion are effective
      in preventing severe bleeding. Our results suggested that low PLT count might be
      the leading cause of fatal bleeding in patients newly diagnosed with APL.

PMID- 29062238
TI  - Structural and functional characterization of the Helicobacter pylori cytidine 5'
      monophosphate-pseudaminic acid synthase PseF: molecular insight into substrate
      recognition and catalysis mechanism.
AB  - The bacterium Helicobacter pylori is a human gastric pathogen that can cause a
      wide range of diseases, including chronic gastritis, peptic ulcer and gastric
      carcinoma. It is classified as a definitive (class I) human carcinogen by the
      International Agency for Research on Cancer. Flagella-mediated motility is
      essential for H. pylori to initiate colonization and for the development of
      infection in human beings. Glycosylation of the H. pylori flagellum with
      pseudaminic acid (Pse; 5,7-diacetamido-3,5,7,9-tetradeoxy-l-glycero-l-manno
      nonulosonic acid) is essential for flagella assembly and function. The sixth step
      in the Pse biosynthesis pathway, activation of Pse by addition of a cytidine 5'
      monophosphate (CMP) to generate CMP-Pse, is catalyzed by a metal-dependent enzyme
      pseudaminic acid biosynthesis protein F (PseF) using cytidine 5'-triphosphate
      (CTP) as a cofactor. No crystal-structural information for PseF is available.
      This study describes the first three-dimensional model of H. pylori PseF obtained
      using biocomputational tools. PseF harbors an alpha/beta-type hydrolase fold with
      a beta-hairpin (HP) dimerization domain. Comparison of PseF with other structural
      homologs allowed identification of crucial residues for substrate recognition and
      the catalytic mechanism. This structural information would pave the way to design
      novel therapeutics to combat bacterial infection.

PMID- 29062240
TI  - A randomized, Phase IIb study investigating oliceridine (TRV130), a novel u
      receptor G-protein pathway selective (MU-GPS) modulator, for the management of
      moderate to severe acute pain following abdominoplasty.
AB  - BACKGROUND: Oliceridine (TRV130), a novel MU-receptor G-protein pathway selective
      (MU-GPS) modulator, was designed to improve the therapeutic window of
      conventional opioids by activating G-protein signaling while causing low beta
      arrestin recruitment to the MU receptor. This randomized, double-blind, patient
      controlled analgesia Phase IIb study was conducted to investigate the efficacy,
      safety, and tolerability of oliceridine compared with morphine and placebo in
      patients with moderate to severe pain following abdominoplasty (NCT02335294;
      oliceridine is an investigational agent not yet approved by the US Food and Drug
      Administration). METHODS: Patients were randomized to receive postoperative
      regimens of intravenous oliceridine (loading/patient-controlled demand doses
      [mg/mg]: 1.5/0.10 [regimen A]; 1.5/0.35 [regimen B]), morphine (4.0/1.0), or
      placebo with treatment initiated within 4 hours of surgery and continued as
      needed for 24 hours. RESULTS: Two hundred patients were treated (n=39, n=39,
      n=83, and n=39 in the oliceridine regimen A, oliceridine regimen B, morphine, and
      placebo groups, respectively). Patients were predominantly female (n=198 [99%])
      and had a mean age of 38.2 years, weight of 71.2 kg, and baseline pain score of
      7.7 (on 11-point numeric pain rating scale). Patients receiving the oliceridine
      regimens had reductions in average pain scores (model-based change in time
      weighted average versus placebo over 24 hours) of 2.3 and 2.1 points,
      respectively (P=0.0001 and P=0.0005 versus placebo); patients receiving morphine
      had a similar reduction (2.1 points; P<0.0001 versus placebo). A lower prevalence
      of adverse events (AEs) related to nausea, vomiting, and respiratory function was
      observed with the oliceridine regimens than with morphine (P<0.05). Other AEs
      with oliceridine were generally dose-related and similar in nature to those
      observed with conventional opioids; no serious AEs were reported with
      oliceridine. CONCLUSION: These results suggest that oliceridine may provide
      effective, rapid analgesia in patients with moderate to severe postoperative
      pain, with an acceptable safety/tolerability profile and potentially wider
      therapeutic window than morphine.

PMID- 29062239
TI  - Cardiac autonomic neuropathy in patients with diabetes mellitus: current
      perspectives.
AB  - Cardiac autonomic neuropathy (CAN) is a common and often-underdiagnosed
      complication of diabetes mellitus (DM). CAN is associated with increased
      mortality, cardiovascular disease, chronic kidney disease, and morbidity in
      patients with DM, but despite these significant consequences CAN often remains
      undiagnosed for a prolonged period. This is commonly due to the disease being
      asymptomatic until the later stages, as well as a lack of easily available
      screening strategies. In this article, we review the latest developments in the
      epidemiology, pathogenesis, diagnosis, consequences, and treatments of CAN in
      patients with DM.

PMID- 29062241
TI  - Interleukin-1 receptor antagonist inhibits angiogenesis via blockage IL
      1alpha/PI3K/NF-kappabeta pathway in human colon cancer cell.
AB  - PURPOSE: This article investigates the relationship between cancer cells and
      stromal cells in carcinoma cell living microenvironment and elucidates the
      mechanism that interleukin-1 receptor antagonist (IL-1RA) blocks metastatic
      potential in colon cancer. METHODS: Western blot and RT-PCR assay were used to
      determine the expression of hepatocyte growth factor (HGF) and IL-1alpha in colon
      carcinoma cells and stromal cells. Effect of IL-1RA and HGF on metastatic
      potential of colon cancer cells were examined by proliferation, invasion, and
      angiogenesis assays. The interactional role of IL-1RA and HGF were detected by
      ELISA assay, invasion, and angiogenesis assay making up a co-culture system
      consisting of stromal and colon cancer cells in cells living microenvironment.
      RESULTS: IL-1alpha was expressed in human umbilical vein endothelial cells
      (HUVECs) and HT-29 and WiDr (colon cancer cell lines with higher liver metastatic
      potential). HGF was expressed only in fibroblast. HGF secretion from fibroblasts
      was significantly inhibited by IL-1RA (P<0.01). Furthermore, IL-1RA could
      significantly inhibit migration, proliferation, and angiogenesis of HUVECs
      (P<0.01). In the double co-culture system, there is a high liver metastatic
      potential of colon cancer cell line (HT-29) because it can secrete autocrine IL
      1alpha, significantly enhanced angiogenesis compared with low liver metastatic
      cell line (CaCo-2) (P<0.01), which does not secrete IL-1alpha. On the contrary,
      blockage of autocrine IL-1alpha by IL-1RA might significantly decrease metastatic
      potential of colon carcinoma cells through downregulation of IL-1alpha/PI3K/NF
      kappaB pathway. CONCLUSION: IL-1 receptor antagonist (IL-1RA) is an important
      inhibitor in metastatic process of colon carcinoma cell. Based on the above
      results, we suggest that IL-1RA may be a promising new therapeutic approach in
      inhibiting colon cancer with IL-1-producing patients.

PMID- 29062242
TI  - Impact of hepatitis C virus genotype-4 eradication following direct acting
      antivirals on liver stiffness measurement.
AB  - BACKGROUND: Liver fibrosis is the most important prognostic factor in chronic
      hepatitis C virus (HCV) patients, and Egypt shows the highest worldwide HCV
      prevalence with genotype-4 pre-dominance. The aim of this study was to
      investigate the degree of liver stiffness measurement (LSM) improvement after
      successful HCV eradication. PATIENTS AND METHODS: The study included 84 chronic
      HCV Egyptian patients, and was conducted at Qena University Hospital from
      November 1, 2015 till October 31, 2016. LSM was obtained by FibroScan(r) before
      starting direct acting antiviral (DAA) treatment and after achieving sustained
      virologic response-24 (SVR-24). Based on baseline LSM, patients were stratified
      into F0-F1, F2, F3 and F4 groups (METAVIR). LSM and laboratory data after
      achieving SVR-24 was compared with that before starting therapy in each fibrosis
      group (F0-F4), p-value <0.05 was statistically significant. RESULTS: Following
      DAA treatment, 80 patients achieved SVR-24; of these, 50 were males (62.5%), mean
      age: 54.2+/-7.6 years, and mean body mass index: 28.6+/-2.2 kg/m2. Mean baseline
      LSM dropped from 15.6+/-10.8 to 12.1+/-8.7 kPa post-SVR; the maximum change of 
      5.8 occurred in F4 versus -2.79, -1.28 and +0.08 in F3, F2 and F0-F1 respectively
      (p<0.0001). At baseline, 41 patients were in the F4 group; only 16 (39%)
      regressed to non-cirrhotic range (<12.5 kPa), while 25 (61%) were still cirrhotic
      despite achieving SVR-24 (p<0.0001). Patients who achieved LSM improvement (n=64)
      have had significantly higher baseline aspartate transferase (AST) and alanine
      transaminase (ALT). Also, those patients showed significant improvement in AST,
      AST/platelets ratio index (APRI) and fibrosis-4 index (Fib-4) after achieving
      SVR; 91% showed AST improvement (p=0.01) and APRI improvement (p=0.01) and 81%
      showed Fib-4 improvement (p=0.04). Females, diabetics, patients with S3 steatosis
      and patients older than 50 years showed less LSM improvements than their
      counterparts. Baseline LSM >=9 kPa, bilirubin >=1 mg/dl, ALT >=36 U/L and AST
      >=31 U/L were significant predictors for LSM improvement. CONCLUSION: Successful
      HCV genotype-4 eradication results in significant LSM improvement; the best
      improvement occurs in F4 patients. But as the majority of cirrhotics are still at
      risk for liver decompensation and hepatocellular carcinoma development despite
      achieving SVR-24, early detection and treatment are highly recommended.

PMID- 29062243
TI  - Frequency-domain optical tomographic image reconstruction algorithm with the
      simplified spherical harmonics (SP3) light propagation model.
AB  - We introduce here the finite volume formulation of the frequency-domain
      simplified spherical harmonics model with n-th order absorption coefficients (FD
      SPN) that approximates the frequency-domain equation of radiative transfer (FD
      ERT). We then present the FD-SPN based reconstruction algorithm that recovers
      absorption and scattering coefficients in biological tissue. The FD-SPN model
      with 3rd order absorption coefficient (i.e., FD-SP3) is used as a forward model
      to solve the inverse problem. The FD-SP3 is discretized with a node-centered
      finite volume scheme and solved with a restarted generalized minimum residual
      (GMRES) algorithm. The absorption and scattering coefficients are retrieved using
      a limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) algorithm. Finally,
      the forward and inverse algorithms are evaluated using numerical phantoms with
      optical properties and size that mimic small-volume tissue such as finger joints
      and small animals. The forward results show that the FD-SP3 model approximates
      the FD-ERT (S12) solution within relatively high accuracy; the average error in
      the phase (<3.7%) and the amplitude (<7.1%) of the partial current at the
      boundary are reported. From the inverse results we find that the absorption and
      scattering coefficient maps are more accurately reconstructed with the SP3 model
      than those with the SP1 model. Therefore, this work shows that the FD-SP3 is an
      efficient model for optical tomographic imaging of small-volume media with non
      diffuse properties both in terms of computational time and accuracy as it
      requires significantly lower CPU time than the FD-ERT (S12) and also it is more
      accurate than the FD-SP1.

PMID- 29062244
TI  - Role of genetics in pediatric rheumatology.
AB  - Pediatric rheumatology includes autoinflammatory monogenic diseases,
      autoinflammatory multifactorial diseases with complex inheritance, and diseases
      with uncertain clinical diagnosis or undefined conditions, even though they show
      signs of autoinflammation. Most of these diseases are systemic; it is important
      to diagnose patients promptly and definitively and to select proper treatment
      options based on the diagnoses. Clinical observation and acute-phase responses
      are usually sufficient for diagnosis; however, genetic analyses can provide
      supportive data for definite diagnosis and treatment, especially for rare
      monogenic diseases. As for multifactorial autoinflammatory diseases,
      susceptibility genes, and factors involved in the etiopathogenesis have not been
      fully identified. It is possible to identify disease genes and novel diseases,
      and lead to new treatment options by gene mapping studies and high-throughput
      screening strategies for multifactorial diseases and conditions with uncertain
      clinical characteristics. In this review, we discuss the three groups of
      autoinflammatory diseases and role of genetics in their diagnosis.

PMID- 29062245
TI  - Research of genetic bases of hereditary non-syndromic hearing loss.
AB  - AIM: Hearing loss is the most common sensory disorder that affects approximately
      one per 1000 live births. With this project, we aimed to identify gene variants
      that were common causes of hearing loss in Turkey to contribute to the planning
      of genetic screening programs for hearing loss, as well as to improve genetic
      counseling to affected families. MATERIAL AND METHODS: Twenty-one families with
      at least two affected individuals and parental consanguinity who presented with
      non-syndromic severe-to-profound sensorineural hearing loss were included in this
      study. We first screened for mutations in GJB2 and mitochondrial DNA 12S RNA
      genes. Subsequently, we genotyped the TMIE c.250C>T and SNP markers flanking the
      SLC26A4, MYO7A, MYO15A, OTOF, CDH23, TMIE, TECTA, PCDH15, TMC1, TMPRSS3, TMHS
      genes in the remaining twelve families without mutations in GJB2. RESULTS:
      Screening for mutations in GJB2 gene showed c.[35delG];[35delG] mutation in four
      families, c.[35delG];[507C>A] mutation in two families, c.[35delG];[-23+1G>A]
      mutation in one family, and c.457G>A heterozygous mutation in one family.
      Genotyping SNP markers showed the c.[250C>T];[250C>T] mutation in TMIE in one
      family. A homozygous region with SNP genotypes was detected with the OTOF gene in
      one family, the TMPRSS3 gene in another family, and also a homozygous region was
      detected with TMHS, OTOF, and TMPRSS3 genes in another family. CONCLUSIONS:
      Further research will be required to determine the genetic bases of hearing loss
      in families with non-syndromic hearing loss.

PMID- 29062246
TI  - Visual-evoked potentials in children and adolescents with newly diagnosed
      diabetes.
AB  - AIM: Central nervous system impairment is common in patients with diabetes, even
      in the early stages of the disease. The aim of the study was to evaluate central
      nerve conduction changes in children and adolescents with newly diagnosed
      diabetes mellitus using pattern-reversal visual-evoked potentials. MATERIAL AND
      METHODS: Pattern-reversal visual-evoked potentials were assessed in 48 patients
      with type 1 (age 11.9+/-2.9 years) and 18 patients with type 2 (age 14.8+/-1.3
      years) diabetes less than a month after diagnosis and in 33 control subjects (age
      12.9+/-3.9 years). RESULTS: P100 latencies were significantly delayed in patients
      with type 1 and 2 diabetes compared with control subjects (p<0.001). There was no
      correlation between P100 latencies and age at diagnosis. No correlations were
      found between P100 latencies and HbA1c values in patients with type 1 diabetes.
      However, P100 latencies were significantly associated with levels of HbA1c in
      patients with type 2 diabetes (p<0.01). There was a marked inter-individual
      variability in amplitudes of N75 to P100 in both patients with diabetes and
      controls. The amplitudes of N75 to P100 were not associated with levels of HbA1c
      in patients with diabetes. Negative correlations between amplitudes of N75 to
      P100 and age at diagnosis were noted in patients with type 1 diabetes (p<0.05).
      CONCLUSIONS: The impaired visual-evoked potential latencies in children and
      adolescents with newly diagnosed diabetes mellitus suggest an early involvement
      of the optic pathway. Visual-evoked potential could be helpful for the early
      detection of central nerve conduction changes at this subclinical stage of the
      disease.

PMID- 29062247
TI  - Frequency of Mycobacterium bovis and mycobacteria in primary immunodeficiencies.
AB  - AIM: Susceptibility to mycobacterial diseases is observed in some primary
      immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial
      infections in primary immunodeficiency diseases. MATERIAL AND METHODS: Patients
      under follow-up by Ege University Pediatric Immunology Department for severe
      combined and combined immunodeficiencies, interleukin 12/ interferon gamma
      receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and
      chronic granulomatosis disease were evaluated retrospectively in terms of the
      frequency and characteristics of mycobacterial infections using a questionnaire
      form for demographic properties, clinical features and laboratory tests. RESULTS:
      A diagnosis of mycobacterial infection was made clinically in a total of 25
      patients including five (11.3%) of 45 patients who had severe combined immune
      deficiency, 12 (52.3%) of 21 patients who had chronic granulomatous disease, four
      patients (100%) who had interferon gamma receptor 2 partical deficiency, two
      patients (100%) who had interleukin 12 receptor beta 1 deficiency and one patient
      (100%) who had nuclear factor kapa-beta essential modulator deficiency.
      Mycobacterium strain could be typed in 14 (33%) of these 25 patients including
      Mycobacterium bovis, Mycobacterium chelonea, Mycobacterium elephantis,
      Mycobacterium fortuitum, and Mycobacterium tuberculosis. All patients were
      treated with anti-tuberculosis therapy. Thirty-six percent of these 25 patients
      underwent hematopoietic stem cell transplantation. Eight patients (five before,
      three after transplantation) died. CONCLUSIONS: Non-tuberculosis mycobacteria
      including mainly Mycobacterium bovis were observed with a higher rate compared to
      Mycobacterium tuberculosis in primary immunodeficiencies, especially in those
      affecting the interleukin 12/interferon gamma pathway. Early diagnosis of primary
      immunodeficiencies with neonatal screening program and preventing administration
      of the Bacille Calmette-Guerin vaccine in these patients is important.

PMID- 29062248
TI  - Evaluation of Candida species and antifungal susceptibilities among children with
      invasive candidiasis.
AB  - AIM: Non-albicans Candida species and resistant microorganisms have been more
      commonly isolated in invasive candidiasis in recent years. The aim of this study
      was to evaluate the distrubution of Candida spp and antifungal resistance in our
      clinic. MATERIAL AND METHODS: Fifty-four Candida isolates and antifungal
      susceptibility results obtained from patients diagnosed as having invasive
      candidiasis between December 2012 and June 2016 were included. Clinical and
      laboratory data were retrospectively analyzed. E-test method was used in order to
      determine antifungal susceptibilities of Candida spp for amphotericin B,
      fluconazole, voriconazole, ketoconazole, itraconazole, anidulafungin,
      caspofungin, and flucytosine. RESULTS: The clinical diagnoses of the patients
      were candidemia (n=27, 50%), catheter-related blood stream infection (n=1, 1.8%),
      urinary tract infection (n=13, 24%), surgical site infection (n=4, 7.4%),
      intraabdominal infection (n=3, 5.5%), empyema (n=2, 3.7%), and pneumonia (n=4,
      7.4%). The most common isolated agent was C. albicans (n=27, 50%) and the others
      were C. parapsilosis (n=13, 24%), C. tropicalis (n=6, 11.1%), C. glabrata (n=3,
      5.6%), C. lusitaniae (n=2, 3.7%), and unspecified Candida spp. (n=3, 5.6%).
      Fluconazole resistance was 7.4% among all isolates. Resistance against
      itraconazole, ketoconazole, anidulafungin, voriconazole and caspofungin were
      33.3%, 12.5%, 11.1%, 5%, and 2.5%, respectively. Isolates presented intermediate
      resistance against itraconazole (41.7%), voriconazole (5.6%), and amphotericin B
      (3.7%) to varying extents. All of the isolates were susceptible to flucytosine.
      CONCLUSIONS: In our clinic, C. albicans and non-albicans Candida species were
      equally distributed and antifungal susceptibilities against major antifungal
      agents such as fluconazole, amphotericin B, and caspofungin were found
      considerably high.

PMID- 29062249
TI  - A retrospective evaluation of blood cultures in a pediatric intensive care unit:
      a three year evaluation.
AB  - AIM: In this study, it was aimed to retrospectively assess the frequency and
      antibiotic resistance of microorganisms isolated from blood cultures of patients
      in a pediatric intensive care unit. MATERIAL AND METHODS: The study was conducted
      on blood culture tests obtained from patients in a pediatric intensive care unit
      and sent to a microbiology laboratory between 2013 and 2016. The species and
      antibiotic susceptibilities were assessed in microorganisms isolated from the
      blood cultures. RESULTS: Overall, 4239 blood cultures were obtained. Growth was
      detected in 324 blood cultures (7.6%). Of the microorganisms isolated, 195
      (60.2%) were Gram-positive bacteria, and 107 (33.0%) were Gram-negative bacteria;
      22 (6.8%) were fungi. The most commonly isolated microorganisms were Coagulase
      negative staphylococci (45.1%), followed by Klebsiella pneumonia (14.5%), and
      Enterococcus faecalis (6.5%). Among the fungi, the most common was Candida
      albicans (59.1%), followed by Candida parapsilosis. The resistance rate against
      methicillin was 89.9% in coagulase-negative staphylococci, and 66% in S. aureus
      strains. The resistance rate against vancomycin was 3.6% in Enterococci spp.
      There was no resistance against linezolid in Gram-positive microorganisms. The
      rate of extended-spectrum beta lactamase positivity was found as 34% in
      Klebsiella spp. and 100% in Escherichia coli. The resistance rate against
      carbapenem was 44.9% in Gram-negative bacteriae. The resistance rate against
      carbapenem was 100% in Acinetobacter baumanii. In Candida albicans, resistance to
      amphotericine B was 61.5%, and resistance to voriconazole was 7.7%. CONCLUSIONS:
      To plan effective empiric antibiotic therapy against nosocomial infections in
      intensive care units, all units should have information about the characteristics
      of their own flora.

PMID- 29062250
TI  - Hyperbilirubinemia due to minor blood group (anti-E) incompatibility in a
      newborn: a case report.
AB  - In addition to Rh and ABO incompatibilities subgroup incompatibilities may rarely
      play a role among the causes of hemolytic anemia and indirect hyperbilirubinemia
      in newborns. The most common minor blood group antigens that cause blood
      incompatibility between the mother and baby are C, c, E, e, Kell, Duffy, Diego,
      Kidd and MNSs antigens. In this article, a newborn in whom hyperbilirubinemia due
      to anti-E minor blood group incompatibility developed and was treated with
      phototherapy succesfully is presented and minor blood group incompatibilities due
      to anti-E are reviewed.

PMID- 29062251
TI  - A congenital cranial dysinnervation disorder: Mobius' syndrome.
AB  - Mobius' syndrome, also known as Mobius' sequence, is a nonprogressive cranial
      dysinnervation disorder characterized by congenital facial and abducens nerve
      paralysis. Here, we report a 5-day-old girl who was conceived after in vitro
      fertilization with poor suck and facial paralysis. She had bilaterally ptosis and
      lateral gaze limitation, left-sided deviation of the tongue, dysmorphic face,
      hypoplastic fingers and finger nails on the left hand, and was diagnosed as
      having Mobius' syndrome. Involvement of other cranial nerves such as three, four,
      five, nine, 9 and 12, and limb malformations may accompany this syndrome.
      However, several factors have been proposed for the etiology, some rare cases
      have also been reported with artificial reproductive technologies. Feeding
      difficulties and aspiration are the main problems encountered in infancy. The
      other cranial nerves should be examined further in newborns who present with
      congenital facial palsy, and other cranial dysinnervation disorders should be
      considered in the differential diagnosis.

PMID- 29062252
TI  - Plasmapheresis in a child with cold antibody autoimmune hemolytic anemia: case
      report.
AB  - Autoimmune hemolytic anemia is a picture of hemolysis which is caused by
      autoantibodies against red blood cell surface antigens. It is classified as
      primary, secondary or warm and cold autoimmune hemolytic anemia according to the
      temperature at which antibodies react. It is usually an acute and self-limiting
      condition. Here, we present a three-year-old male patient who presented with
      malaise, paleness, and dark-colored urine. His hemoglobin level was 5.8 g/dL, and
      increased indirect bilirubin and lactate dehydrogenase levels and decreased
      haptoglobulin and reticulocyte levels were noted. A direct Coombs test was
      positive using anti-C3. Four erythrocyte suspension transfusions were given
      because the anemia was life-threatening. High-dose steroids (30 mg/kg/ day,
      methylprednisolone) and intravenous immunoglobulin (1 g/kg/day, two days)
      treatments were unresponsive. Plasmapheresis was performed and no further
      transfusions were needed after plasmapheresis. Plasmapheresis treatment can be
      effective in children with cold type autoimmune hemolytic anemia.

PMID- 29062253
TI  - Gorlin-Goltz syndrome.
AB  - Gorlin-Goltz syndrome is a rare multisystemic disease inherited in an autosomal
      dominant pattern. It is characterized by numerous basal cell carcinoma of the
      skin, jaw cysts, and skeletal anomalies such as frontal bossing, vertebral
      anomalies, palmoplantar pits, and falx cerebri calcification. There is a tendency
      to tumors including medullablastoma, fibroma, rabdomyoma, leiomyosarcoma etc..
      The diagnosis is based on major and minor clinical and radiologic criteria. Early
      diagnosis and treatment are of utmost importance in reducing the severity of long
      term sequelae of this syndrome. In this article, we present a 15-year-old boy who
      was admitted to our clinic with brown-black papules and plaques on his scalp and
      was thought to have Gorlin-Goltz syndrome. He had a history of medulloblastoma
      that was treated with surgical resection followed by cranial radiotherapy and
      unilateral retinoblastoma. We present this case, because association of Gorlin
      Goltz syndrome and retinoblastoma has not been described previously in the
      literature and we aimed to draw attention to radiation-induced basal cell
      carcinomas.

PMID- 29062254
TI  - Erroneous diagnosis of rickets.

PMID- 29062255
TI  - Epidemiology of hepatitis E virus in children.

PMID- 29062256
TI  - Re: Epidemiology of hepatitis E virus in children.

PMID- 29062257
TI  - HLA genes as a predictive screening tool for celiac disease.

PMID- 29062258
TI  - Re: HLA genes as a predictive screening tool for celiac disease.

PMID- 29062259
TI  - Impact of soil salinity on the plant-growth - promoting and biological control
      abilities of root associated bacteria.
AB  - The effectiveness of plant growth - promoting bacteria is variable under
      different biotic and abiotic conditions. Abiotic factors may negatively affect
      the beneficial properties and efficiency of the introduced PGPR inoculants. The
      aim of this study was to evaluate the effect of plant growth - promoting
      rhizobacteria on plant growth and on the control of foot and root rot of tomatoes
      caused by Fusarium solani under different soil salinity conditions. Among the
      five tested strains, only Pseudomonas chlororaphis TSAU13, and Pseudomonas
      extremorientalis TSAU20 were able to stimulate plant growth and act as biological
      controls of foot and root rot disease of tomato. The soil salinity did not
      negatively affect the beneficial impacts of these strains, as they were able to
      colonize and survive on the roots of tomato plants under both saline and non
      saline soil conditions. The improved plant height and fruit yield of tomato was
      also observed for plants inoculated with P. extremorientalis TSAU20. Our results
      indicated that, saline condition is not crucial factor in obtaining good
      performance with respect to the plant growth stimulating and biocontrol abilities
      of PGPR strains. The bacterial inoculant also enhanced antioxidant enzymes
      activities thereby preventing ROS induced oxidative damage in plants, and the
      proline concentrations in plant tissue that play an important role in plant
      stress tolerance.

PMID- 29062260
TI  - Morphological observation and characterization of the Pseudoregma bambucicola
      with the scanning electron microscope.
AB  - Both leica microscopic camera system and scanning electron microscopy was used to
      observe and characterize the feet, back, abdomen, antennae and mouthparts of the
      Pseudoregma bambucicola from the bamboo, Bambusa multiplex. The possible
      functions of all the external morphological characteristics of the P. bambucicola
      were described and discussed in detail, which offers a basis for further
      enriching the biology, phylogeny and ecological niche of the P. bambucicola.
      Moreover, the morphological results should contribute to morphological
      identification and differentiation of the P. bambucicola from other aphids in the
      same family.

PMID- 29062261
TI  - A pandemic risk assessment of middle east respiratory syndrome coronavirus (MERS
      CoV) in Saudi Arabia.
AB  - Since the initial emergence of Middle East respiratory syndrome coronavirus (MERS
      CoV) in 2012, a high incidence rate has been observed in Saudi Arabia. This
      suggests that the country is at continuous risk. The epidemic level of MERS-CoV
      infection was examined in Saudi Arabia by the Susceptible-Infectious-Recovered
      (SIR) model using a Bayesian approach for estimation of time dependent
      reproduction number (R) across a two-year interval (May, 2013-May, 2015) in five
      defined clusters, followed by sensitivity analysis of the most significant
      clusters. Significant MERS-CoV peaks were detected in the period between March
      and May of each year. Moreover, MERS-CoV infection was highlighted in western
      (40.8%) and central (31.9%) regions, followed by eastern region (20%). The
      temporal-based Bayesian approach indicated a sub-critical epidemic in all regions
      in the baseline scenario (R: 0.85-0.97). However, R potential limit was exceeded
      in the sensitivity analysis scenario in only central and western regions (R: 1.08
      1.12) that denoted epidemic level in those regions. The impact of sporadic cases
      was found relatively insignificant and pinpointed to the lack of zoonotic
      influence on MERS-CoV transmission dynamics. The results of current study would
      be helpful for evaluation of future progression of MERS-CoV infections, better
      understanding and control interventions.

PMID- 29062262
TI  - The morpho-agronomic characterization study of Lens culinaris germplasm under
      salt marsh habitat in Swat, Pakistan.
AB  - The present research study evaluate and identify the most suitable and high
      yielding genotypes of Lens culinaris for the salt marsh habitat of Swat in moist
      temperate sort of agro climatic environment of Pakistan. A total of fourteen
      genotypes were cultivated and analyzed through Randomized Complete Block Design
      (RCBD). These genotypes were AZRC-4, NL-2, NL4, NL-5, NL-6, NARC-11-1, NARC-11-2,
      NARC-11-3, NARC-11-4, 09503, 09505, 09506, P.Masoor-09 and Markaz-09. Different
      parameters i.e., germination rate, flowering, physiological maturity, plant
      height, biological grain yield, seed weight, pods formation and its height, pods
      per plants and protein content were focused specially throughout the study.
      Preliminary the Lentil genotypes have significant variability in all the major
      morpho-agronomic traits. The days to germination, 50% flowering and 100 seed
      weight ranged from 7 to 9, 110 to 116 days, and from 5.4 to 7.3 gm respectively.
      Biological yield and grain yield ranged from 5333 to 9777 kg ha-1 and 1933 to
      3655 kg ha-1 respectively. Whereas, protein contents ranged from 23.21% to
      28.45%. It was concluded that the genotype AZRC-4 is better varity in terms of
      grain yield plus in 100 seed weight and moreover, 09506 genotype was significant
      under salt marsh habitat in early maturing for the Swat Valley, Pakistan.

PMID- 29062263
TI  - Indigofera oblongifolia leaf extract regulates spleen macrophage response during
      Plasmodium chabaudi infection.
AB  - Malaria is a major health problem that still affects numerous countries. The
      current study aimed to identify the role of Indigofera oblongifolia leaf extract
      in regulating mouse spleen macrophages during the progression of Plasmodium
      chabaudi infection. Three doses of the leaf extract (100, 200, and 300 mg/kg)
      were administered to mice inoculated with P. chabaudi infected erythrocytes. The
      weight of the infected mice improved after the treatment with I. oblongifolia.
      The infection causes disorganization of macrophage distribution in the spleen.
      After the mice had been treated with the leaf extract, the macrophages appeared
      to be reorganized in the white and red pulp areas. In addition, the I.
      oblongifolia leaf extract (IOLE) significantly increased the total antioxidant
      capacity of the mice spleens infected with P. chabaudi. The phagocytic activity
      of spleen macrophages was increased in the infected group as indicated by the
      significant decrease in the number of fluorescent particles in the spleen
      sections. This number increased in the mice spleens after treatment with IOLE.
      Based on these results, it is suggested that IOLE regulate macrophage response of
      the spleen during the blood stage of malaria in mice.

PMID- 29062264
TI  - Characteristics of PM2.5 Concentrations across Beijing during 2013-2015.
AB  - High concentrations of particulate matter (PM2.5) and frequent air pollution
      episodes in Beijing have attracted widespread attention. This paper utilizes data
      from the new air pollution network in China to examine the current spatial and
      temporal variability of PM2.5 at 12 monitoring sites in Beijing over a recent 2
      year period (April 2013) to March 2015). The long term (2-year) average
      concentration was 83 ug.m-3, well above Chinese and international standards.
      Across the region, annual average concentrations varied by 20 ug.m-3 (25% of the
      average level), with lower levels in suburban areas compared to periurban and
      urban areas, which had similar concentrations. The spatial variation in PM2.5
      concentrations was associated with several land use and economic variables,
      including the fraction of vegetated land and building construction activity,
      which together explained 71% of the spatial variation. Daily air quality was
      characterized as "polluted" (above 75 ug.m-3) on 36 to 47% of days, depending on
      site. There were 77 pollution episodes during the study period (defined as two or
      more consecutive days with Beijing-wide 24-hour average concentrations over 75
      ug.m-3), and 2 to 5 episodes occurred each month, including summer months. The
      longest episode lasted 9 days and daily concentrations exceeded 450 ug.m-3. Daily
      PM2.5 levels were autocorrelated (rlag1 = 0.516) and associated with many
      meteorological variables, including barometric pressure, relative humidity, hours
      of sunshine, surface and ambient temperature, precipitation and scavenging
      coefficient, and wind direction. Parsimonious models with meteorological and
      autoregressive terms explained over 60% of the variation in daily PM2.5 levels.
      The first autoregressive term and hours of sunshine were the most important
      variables in these models, however, the latter variable is PM2.5-dependent and
      thus not an explanatory variable. The present study can serve as a baseline to
      compare the improved air quality in Beijing expected in future years.

PMID- 29062265
TI  - Relations between Attorney Temporal Structure and Children's Response
      Productivity in Cases of Alleged Child Sexual Abuse.
AB  - PURPOSE: Previous research has demonstrated that attorney question format relates
      to child witness' response productivity. However, little work has examined the
      relations between the extent to which attorneys provide temporal structure in
      their questions, and the effects of this structure on children's responding. The
      purpose of the present study was to address this gap in the literature in order
      to identify methods by which attorneys increase children's response productivity
      on the stand without risking objections from opposing counsel for "calling for
      narrative answers". METHODS: In the present study we coded criminal court
      transcripts involving child witnesses (5-18 years) for narrative structure in
      attorney questions and productivity in children's responses. Half of the
      transcripts resulted in convictions, half in acquittals, balanced across key
      variables: child age, allegation severity, the child's relationship to the
      perpetrator, and the number of allegations. RESULTS: Prosecutors and defense
      attorneys varied substantially in their questioning tactics. Prosecutors used
      more temporal structure in their questions and varied their questioning by the
      age of the child. These variations had implications for children's response
      productivity. CONCLUSIONS: Results indicate that temporal structure is a novel
      and viable method for enhancing children's production of case-relevant details on
      the witness stand.

PMID- 29062266
TI  - Parental Alcohol Use, Parenting, and Child On-Time Development.
AB  - This study examined whether parental alcohol use in adolescence, adulthood, and,
      for mothers, during pregnancy was related to their young children's functioning
      in terms of their on-time development as indicated by the number of developmental
      areas in which children experienced delay. Observed parenting practices and
      family socioeconomic status were tested as potential explanatory mechanisms of
      these links. Data came from the surveys and videotaped observations of a
      community sample of 123 biological parents and their 1-5 year old children
      followed longitudinally. Results suggest that the negative association between
      parental alcohol use and children's development operates primarily through
      fathers' alcohol use. Additionally, father's adolescent regular alcohol use
      predicted the family's low SES, which in turn predicted less-skilled maternal
      parenting practices and children's developmental delay.

PMID- 29062267
TI  - Design and Preliminary Feasibility Study of a Soft Robotic Glove for Hand
      Function Assistance in Stroke Survivors.
AB  - Various robotic exoskeletons have been proposed for hand function assistance
      during activities of daily living (ADL) of stroke survivors. However, traditional
      exoskeletons involve the use of complex rigid systems that impede the natural
      movement of joints, and thus reduce the wearability and cause discomfort to the
      user. The objective of this paper is to design and evaluate a soft robotic glove
      that is able to provide hand function assistance using fabric-reinforced soft
      pneumatic actuators. These actuators are made of silicone rubber which has an
      elastic modulus similar to human tissues. Thus, they are intrinsically soft and
      compliant. Upon air pressurization, they are able to support finger range of
      motion (ROM) and generate the desired actuation of the finger joints. In this
      work, the soft actuators were characterized in terms of their blocked tip force,
      normal and frictional grip force outputs. Combining the soft actuators and
      flexible textile materials, a soft robotic glove was developed for grasping
      assistance during ADL for stroke survivors. The glove was evaluated on five
      healthy participants for its assisted ROM and grip strength. Pilot test was
      performed in two stroke survivors to evaluate the efficacy of the glove in
      assisting functional grasping activities. Our results demonstrated that the
      actuators designed in this study could generate desired force output at a low air
      pressure. The glove had a high kinematic transparency and did not affect the
      active ROM of the finger joints when it was being worn by the participants. With
      the assistance of the glove, the participants were able to perform grasping
      actions with sufficient assisted ROM and grip strength, without any voluntary
      effort. Additionally, pilot test on stroke survivors demonstrated that the
      patient's grasping performance improved with the presence and assistance of the
      glove. Patient feedback questionnaires also showed high level of patient
      satisfaction and comfort. In conclusion, this paper has demonstrated the
      possibility of using soft wearable exoskeletons that are more wearable,
      lightweight, and suitable to be used on a daily basis for hand function
      assistance of stroke survivors during activities of daily living.

PMID- 29062268
TI  - Comparison of Diffusion-Weighted MRI Reconstruction Methods for Visualization of
      Cranial Nerves in Posterior Fossa Surgery.
AB  - Diffusion-weighted imaging (DWI)-based tractography has gained increasing
      popularity as a method for detailed visualization of white matter (WM) tracts.
      Different imaging techniques, and more novel, advanced imaging methods provide
      significant WM structural detail. While there has been greater focus on improving
      tract visualization for larger WM pathways, the relative value of each method for
      cranial nerve reconstruction and how this methodology can assist surgical
      decision-making is still understudied. Images from 10 patients with posterior
      fossa tumors (4 male, mean age: 63.5), affecting either the trigeminal nerve (CN
      V) or the facial/vestibular complex (CN VII/VIII), were employed. Three distinct
      reconstruction methods [two tensor-based methods: single diffusion tensor
      tractography (SDT) (3D Slicer), eXtended streamline tractography (XST), and one
      fiber orientation distribution (FOD)-based method: streamline tractography using
      constrained spherical deconvolution (CSD)-derived estimates (MRtrix3)], were
      compared to determine which of these was best suited for use in a neurosurgical
      setting in terms of processing speed, anatomical accuracy, and accurate depiction
      of the relationship between the tumor and affected CN. Computation of the tensor
      map was faster when compared to the implementation of CSD to provide estimates of
      FOD. Both XST and CSD-based reconstruction methods tended to give more detailed
      representations of the projections of CN V and CN VII/VIII compared to SDT. These
      reconstruction methods were able to more accurately delineate the course of CN V
      and CN VII/VIII, differentiate CN V from the cerebellar peduncle, and delineate
      compression of CN VII/VIII in situations where SDT could not. However, CSD-based
      reconstruction methods tended to generate more invalid streamlines. XST offers
      the best combination of anatomical accuracy and speed of reconstruction of
      cranial nerves within this patient population. Given the possible anatomical
      limitations of single tensor models, supplementation with more advanced tensor
      based reconstruction methods might be beneficial.

PMID- 29062269
TI  - Reduced Apparent Diffusion Coefficient in Various Brain Areas following Low
      Intensity Transcranial Ultrasound Stimulation.
AB  - Diffusion of water molecules closely related to physiological and pathological
      information of brain tissue. Low-intensity transcranial ultrasound stimulation
      (TUS) has advantages of noninvasive, high spatial resolution and penetration
      depth. Previous studies have demonstrate that TUS can modulate neuronal activity
      and alter cortical hemodynamic. However, how TUS affect diffusion of water
      molecules remain unclear. In this paper, in order to evaluate the effect of low
      intensity TUS on the diffusion of water molecules in brain tissue, diffusion
      weighted magnetic resonance (MR) imaging was performed in 19 healthy Sprague
      Dawley rats in sham surgery group (six rats) and TUS group (thirteen rats)
      Subsequently, rats were stimulated by low-intensity transcranial ultrasound for 5
      min in TUS group. Finally, rats of sham surgery group and TUS group were imaged
      again by diffusion-weighted MR imaging. The apparent diffusion coefficient (ADC)
      was measured in caudate putamen region and middle brain motor-related region of
      each rat in sham surgery group and TUS group. Surgery-related and TUS-related
      changes were calculated using a statistical analysis. The mean ADC values of
      marked regions of six rats in sham surgery group were 0.743 +/- 0.031 (pre
      surgery) and 0.745 +/- 0.029 (post-surgery). The mean ADC values of marked
      regions of 13 rats in TUS group were 0.749 +/- 0.032 (pre-TUS) and 0.712 +/-
      0.033 (post-TUS) Compared to the pre-TUS values, the mean ADC values of the rats
      decreased 4.9% (*P < 0.05) post-TUS. These results of this study demonstrate that
      low-intensity TUS can restrict the diffusion of water molecules in brain tissue.

PMID- 29062270
TI  - The GlyR Extracellular beta8-beta9 Loop - A Functional Determinant of Agonist
      Potency.
AB  - Ligand-binding of Cys-loop receptors results in rearrangements of extracellular
      loop structures which are further translated into the tilting of membrane
      spanning helices, and finally opening of the ion channels. The cryo-EM structure
      of the homopentameric alpha1 glycine receptor (GlyR) demonstrated an involvement
      of the extracellular beta8-beta9 loop in the transition from ligand-bound
      receptors to the open channel state. Recently, we identified a functional role of
      the beta8-beta9 loop in a novel startle disease mouse model shaky. The mutation
      of residue GlyRalpha1Q177 to lysine present in shaky mice resulted in reduced
      glycine potency, reduced synaptic expression, and a disrupted hydrogen network at
      the structural level around position GlyRalpha1Q177. Here, we investigated the
      role of amino acid volume, side chain length, and charge at position Q177 to get
      deeper insights into the functional role of the beta8-beta9 loop. We used a
      combined approach of in vitro expression analysis, functional
      electrophysiological recordings, and GlyR modeling to describe the role of Q177
      for GlyR ion channel function. GlyRalpha1Q177 variants do not disturb ion channel
      transport to the cellular surface of transfected cells, neither in homomeric nor
      in heteromeric GlyR configurations. The EC50 values were increased for all
      GlyRalpha1Q177 variants in comparison to the wild type. The largest decrease in
      glycine potency was observed for the variant GlyRalpha1Q177R. Potencies of the
      partial agonists beta-alanine and taurine were also reduced. Our data are further
      supported by homology modeling. The GlyRalpha1Q177R variant does not form
      hydrogen bonds with the surrounding network of residue Q177 similar to the
      substitution with a basic lysine present in the mouse mutant shaky. Among all
      investigated Q177 mutants, the neutral exchange of glutamine to asparagine as
      well as the introduction of the closely related amino acid glutamic acid preserve
      the hydrogen bond network. Introduction of amino acids with small side chains or
      larger volume resulted in a loss of their hydrogen bonds to neighboring residues.
      The beta8-beta9 loop is thus an important structural and functional determinant
      of the inhibitory GlyR.

PMID- 29062272
TI  - Obesity Increases Mitogen-Activated Protein Kinase Phosphatase-3 Levels in the
      Hypothalamus of Mice.
AB  - Mitogen-activated Protein Kinase Phosphatase 3 (MKP-3) has been involved in the
      negative regulation of insulin signaling. The absence of MKP-3 is also associated
      with reduced adiposity, increased energy expenditure and improved insulin
      sensitivity. The MKP-3 is known as the main Erk1/2 phosphatase and FoxO1
      activator, which has repercussions on the gluconeogenesis pathway and
      hyperglycemia in obese mice. Recently, we showed that MKP-3 overexpression
      decreases FoxO1 phosphorylation in the hypothalamus of lean mice. However, the
      hypothalamic interaction between MKP-3 and FoxO1 during obesity was not
      investigated yet. Here, the MKP-3 expression and the effects on food intake and
      energy expenditure, were investigated in high-fat diet-induced obese mice. The
      results indicate that obesity in mice increased the MKP-3 protein content in the
      hypothalamus. This hypothalamic upregulation led to an increase of food intake,
      adiposity, and body weight. Furthermore, the obese mice with increased MKP-3
      showed an insulin signaling impairment with reduction of insulin-induced FoxO1
      and Erk1/2 phosphorylation in the hypothalamus. Moreover, a bioinformatics
      analysis of data demonstrated that hypothalamic MKP-3 mRNA levels were positively
      correlated with body weight and negatively correlated to oxygen consumption (VO2)
      in BXD mice. Taken together, our study reports that obesity is associated with
      increased protein levels of hypothalamic MKP-3, which is related to the reduction
      of FoxO1 and Erk1/2 phosphorylation in the hypothalamus as well as to an increase
      in body weight and a reduction in energy expenditure.

PMID- 29062271
TI  - Aminoglycoside-Induced Cochleotoxicity: A Review.
AB  - Aminoglycoside antibiotics are used as prophylaxis, or urgent treatment, for many
      life-threatening bacterial infections, including tuberculosis, sepsis,
      respiratory infections in cystic fibrosis, complex urinary tract infections and
      endocarditis. Although aminoglycosides are clinically-essential antibiotics, the
      mechanisms underlying their selective toxicity to the kidney and inner ear
      continue to be unraveled despite more than 70 years of investigation. The
      following mechanisms each contribute to aminoglycoside-induced toxicity after
      systemic administration: (1) drug trafficking across endothelial and epithelial
      barrier layers; (2) sensory cell uptake of these drugs; and (3) disruption of
      intracellular physiological pathways. Specific factors can increase the risk of
      drug-induced toxicity, including sustained exposure to higher levels of ambient
      sound, and selected therapeutic agents such as loop diuretics and glycopeptides.
      Serious bacterial infections (requiring life-saving aminoglycoside treatment)
      induce systemic inflammatory responses that also potentiate the degree of
      ototoxicity and permanent hearing loss. We discuss prospective clinical
      strategies to protect auditory and vestibular function from aminoglycoside
      ototoxicity, including reduced cochlear or sensory cell uptake of
      aminoglycosides, and otoprotection by ameliorating intracellular cytotoxicity.

PMID- 29062273
TI  - Extracting Neural Oscillation Signatures of Laser-Induced Nociception in Pain
      Related Regions in Rats.
AB  - Previous studies have shown that multiple brain regions are involved in pain
      perception and pain-related neural processes by forming a functionally connected
      pain network. It is still unclear how these pain-related brain areas actively
      work together to generate the experience of pain. To get a better insight into
      the pain network, we implanted electrodes in four pain-related areas of rats
      including the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC),
      primary somatosensory cortex (S1) and periaqueductal gray (PAG). We analyzed the
      pattern of local field potential (LFP) oscillations under noxious laser
      stimulations and innoxious laser stimulations. A high-dimensional feature matrix
      was built based on the LFP characters for both experimental conditions.
      Generalized linear models (GLMs) were trained to classify recorded LFPs under
      noxious vs. innoxious condition. We found a general power decrease in alpha and
      beta bands and power increase in gamma band in the recorded areas under noxious
      condition. After noxious laser stimulation, there was a consistent change in LFP
      power and correlation in all four brain areas among all 13 rats. With GLM
      classifiers, noxious laser trials were distinguished from innoxious laser trials
      with high accuracy (86%) using high-dimensional LFP features. This work provides
      a basis for further research to examine which aspects (e.g., sensory, motor or
      affective processes) of noxious stimulation should drive distinct neural activity
      across the pain network.

PMID- 29062275
TI  - Exploring the Role of Spatial Frequency Information during Neural Emotion
      Processing in Human Infants.
AB  - Enhanced attention to fear expressions in adults is primarily driven by
      information from low as opposed to high spatial frequencies contained in faces.
      However, little is known about the role of spatial frequency information in
      emotion processing during infancy. In the present study, we examined the role of
      low compared to high spatial frequencies in the processing of happy and fearful
      facial expressions by using filtered face stimuli and measuring event-related
      brain potentials (ERPs) in 7-month-old infants (N = 26). Our results revealed
      that infants' brains discriminated between emotional facial expressions
      containing high but not between expressions containing low spatial frequencies.
      Specifically, happy faces containing high spatial frequencies elicited a smaller
      Nc amplitude than fearful faces containing high spatial frequencies and happy and
      fearful faces containing low spatial frequencies. Our results demonstrate that
      already in infancy spatial frequency content influences the processing of facial
      emotions. Furthermore, we observed that fearful facial expressions elicited a
      comparable Nc response for high and low spatial frequencies, suggesting a robust
      detection of fearful faces irrespective of spatial frequency content, whereas the
      detection of happy facial expressions was contingent upon frequency content. In
      summary, these data provide new insights into the neural processing of facial
      emotions in early development by highlighting the differential role played by
      spatial frequencies in the detection of fear and happiness.

PMID- 29062276
TI  - Enhancing Innovation and Underlying Neural Mechanisms Via Cognitive Training in
      Healthy Older Adults.
AB  - Non-invasive interventions, such as cognitive training (CT) and physical
      exercise, are gaining momentum as ways to augment both cognitive and brain
      function throughout life. One of the most fundamental yet little studied aspects
      of human cognition is innovative thinking, especially in older adults. In this
      study, we utilize a measure of innovative cognition that examines both the
      quantity and quality of abstracted interpretations. This randomized pilot trial
      in cognitively normal adults (56-75 years) compared the effect of cognitive
      reasoning training (SMART) on innovative cognition as measured by Multiple
      Interpretations Measure (MIM). We also examined brain changes in relation to MIM
      using two MRI-based measurement of arterial spin labeling (ASL) to measure
      cerebral blood flow (CBF) and functional connectivity MRI (fcMRI) to measure
      default mode and central executive network (CEN) synchrony at rest. Participants
      (N = 58) were randomized to the CT, physical exercise (physical training, PT) or
      control (CN) group where CT and PT groups received training for 3 h/week over 12
      weeks. They were assessed at baseline-, mid- and post-training using innovative
      cognition and MRI measures. First, the CT group showed significant gains pre- to
      post-training on the innovation measure whereas the physical exercise and control
      groups failed to show significant gains. Next, the CT group showed increased CBF
      in medial orbitofrontal cortex (mOFC) and bilateral posterior cingulate cortex
      (PCC), two nodes within the Default Mode Network (DMN) compared to physical
      exercise and control groups. Last, significant correlations were found between
      innovation performance and connectivity of two major networks: CEN (positive
      correlation) and DMN (negative correlation). These results support the view that
      both the CEN and DMN are important for enhancement of innovative cognition. We
      propose that neural mechanisms in healthy older adults can be modified through
      reasoning training to better subserve enhanced innovative cognition.

PMID- 29062277
TI  - Preprocessing of 18F-DMFP-PET Data Based on Hidden Markov Random Fields and the
      Gaussian Distribution.
AB  - 18F-DMFP-PET is an emerging neuroimaging modality used to diagnose Parkinson's
      disease (PD) that allows us to examine postsynaptic dopamine D2/3 receptors. Like
      other neuroimaging modalities used for PD diagnosis, most of the total intensity
      of 18F-DMFP-PET images is concentrated in the striatum. However, other regions
      can also be useful for diagnostic purposes. An appropriate delimitation of the
      regions of interest contained in 18F-DMFP-PET data is crucial to improve the
      automatic diagnosis of PD. In this manuscript we propose a novel methodology to
      preprocess 18F-DMFP-PET data that improves the accuracy of computer aided
      diagnosis systems for PD. First, the data were segmented using an algorithm based
      on Hidden Markov Random Field. As a result, each neuroimage was divided into 4
      maps according to the intensity and the neighborhood of the voxels. The maps were
      then individually normalized so that the shape of their histograms could be
      modeled by a Gaussian distribution with equal parameters for all the neuroimages.
      This approach was evaluated using a dataset with neuroimaging data from 87
      parkinsonian patients. After these preprocessing steps, a Support Vector Machine
      classifier was used to separate idiopathic and non-idiopathic PD. Data
      preprocessed by the proposed method provided higher accuracy results than the
      ones preprocessed with previous approaches.

PMID- 29062278
TI  - Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage in Silico and
      in Vitro.
AB  - DNA topoisomerases 1 and 2 are enzymes that maintain DNA topology and play
      important essential genome functions, including DNA replication and
      transcription. Aberrant topoisomerases cause genome instability and a wide range
      of diseases, cancer in particular. Both Topo 1 and 2 are the targets of valuable
      anticancer drugs, such as camptothecin. It has been previously shown that
      artemisinin, a sesquiterpene lactone from Artemisia annua L. also known as
      qinghaosu, possesses anti-cancer effects and one of its derivatives, artesunate
      inhibits Topo 2. In this study, we evaluated artemisinin and 40 derivatives as
      potential Topo 1 inhibitors at first by in silico molecular docking analyses.
      Five compounds that showed comparable binding energies and similar docking poses
      were selected for in vitro cytotoxicity test and Comet assay for DNA damage. WWLL
      013, WWLL-022, and WWLL-1098 showed the lowest binding energy also induced DNA
      damage in the Comet assay. CMK-0298 and CMK-0398 intercalated into DNA and
      induced mild DNA damage. All selected compounds, WWLL-013 in particular, were
      more cytotoxic toward the rat tumor cells than to the normal cells. In
      conclusion, the artemisinin derivatives such as CMK-0298, CMK-0398, WWLL-013,
      WWLL-022, and WWLL-1098 can be further developed as Topo 1 inhibitors.

PMID- 29062279
TI  - Probiotics for Preventing Ventilator-Associated Pneumonia in Mechanically
      Ventilated Patients: A Meta-Analysis with Trial Sequential Analysis.
AB  - Background and Objective: Ventilator-associated pneumonia (VAP) is still an
      important cause of morbidity and mortality in mechanically ventilated patients.
      The efficacy of the probiotics for preventing VAP is still controversial. Present
      study was conducted to comprehensively evaluate the effect of probiotics on VAP
      prevention in mechanically ventilated patients. Methods: PubMed, Embase, and
      CENTRAL were searched up to September 2016. Eligible trials designed with
      randomized controlled trials (RCTs) comparing probiotics with control in
      mechanically ventilated patients were included. Risk ratios (RRs) and mean
      differences (MDs) with 95% confidence intervals (CIs) were estimated with fixed
      or random effects models. Trial sequential analysis (TSA) was performed using TSA
      0.9beta software. Results: Thirteen RCTs (N = 1969) were included. Overall,
      probiotics were associated with reduced incidence of VAP (RR = 0.73, 95% CI =
      0.60-0.89; P = 0.002), which was confirmed by TSA (TSA adjusted 95% CI = 0.55
      0.96). However, no significant difference was observed in 90-day mortality (RR =
      1.00, 95% CI = 0.72-1.37; P = 0.99), overall mortality (RR = 0.84, 95% CI = 0.70
      1.02; P = 0.09), 28-day mortality (RR = 1.06, 95% CI = 0.72-1.57; P = 0.99),
      intensive care unit (ICU) mortality (RR = 0.97, 95% CI = 0.74-1.27; P = 0.82),
      hospital mortality (RR = 0.81, 95% CI = 0.65-1.02; P = 0.07), diarrhea (RR =
      0.99, 95% CI = 0.83-1.19; P = 0.92), length of ICU stay (MD = -2.40 days, 95% CI
      = -6.75 to 1.95; P = 0.28), length of hospital stay (MD = -1.34 days, 95% CI = 
      6.21 to 3.54; P = 0.59), and duration of mechanical ventilation (MD = -3.32 days,
      95% CI = -6.74 to 0.09; P = 0.06). Conclusions: In this meta-analysis, we found
      that probiotics could reduce the incidence of VAP in mechanically ventilated
      patients. It seems likely that probiotics provide clinical benefits for
      mechanically ventilated patients.

PMID- 29062274
TI  - Monoaminergic Modulation of Motor Cortex Function.
AB  - Elaboration of appropriate responses to behavioral situations rests on the
      ability of selecting appropriate motor outcomes in accordance to specific
      environmental inputs. To this end, the primary motor cortex (M1) is a key
      structure for the control of voluntary movements and motor skills learning.
      Subcortical loops regulate the activity of the motor cortex and thus contribute
      to the selection of appropriate motor plans. Monoamines are key mediators of
      arousal, attention and motivation. Their firing pattern enables a direct encoding
      of different states thus promoting or repressing the selection of actions adapted
      to the behavioral context. Monoaminergic modulation of motor systems has been
      extensively studied in subcortical circuits. Despite evidence of converging
      projections of multiple neurotransmitters systems in the motor cortex pointing to
      a direct modulation of local circuits, their contribution to the execution and
      learning of motor skills is still poorly understood. Monoaminergic dysregulation
      leads to impaired plasticity and motor function in several neurological and
      psychiatric conditions, thus it is critical to better understand how monoamines
      modulate neural activity in the motor cortex. This review aims to provide an
      update of our current understanding on the monoaminergic modulation of the motor
      cortex with an emphasis on motor skill learning and execution under physiological
      conditions.

PMID- 29062281
TI  - Maternal Heart Rate Variability during the First Stage of Labor.
AB  - Labor necessitates continuous adjustments of cardiac autonomic reflexes by
      alternate activation of the sympathetic and parasympathetic nervous systems. The
      division of the autonomic nervous system (ANS) that predominates during the first
      stage of labor is unclear and needs to be further investigated. The study aimed
      to compare heart rate variability (HRV) in pregnant women in the third trimester
      with those during the first stage of labor. We conducted a case-control study at
      Saad Abul Ela Maternity Hospital, Khartoum, Sudan. Forty-five women with
      singleton, live neonates in the first stage of labor and 45 women in the third
      trimester (but not in labor) were enrolled as case and control groups,
      respectively. Data on the medical history, obstetrics history, and clinical
      examinations that were performed in all of the studied women were obtained using
      prearranged questionnaires. Cardiac autonomic modulation (CAM) of the heart was
      examined in both groups based on time and frequency domain HRV indices. There
      were no significant differences in age, parity, body mass index, and hemoglobin
      levels between the two groups. Pregnant women in labor had significantly higher
      LnSDNN, LnRMSSD, LnTP, LnVLF, LnLF, LnHF, LF Norm, and LnLF/HF ratio, but lower
      HF Norm compared with controls (P < 0.001). These findings remained unchanged
      when possible confounders were controlled for using regression analysis. Our
      findings suggest a significant increase in indictors of sympathetic CAM, namely
      LF Norm and LnLF/HF, during labor. Sympathetic hypertonia associated with labor
      is unlikely to increase the risk of cardiac events because sympathetic CAM
      simultaneously increases with global HRV. Increased HRV during labor may be
      explained by parasympathetic activation as indicated by higher LnHF and LnRMSSD
      at the time of delivery.

PMID- 29062280
TI  - Heat and Dehydration Additively Enhance Cardiovascular Outcomes following
      Orthostatically-Stressful Calisthenics Exercise.
AB  - Exercise and exogenous heat each stimulate multiple adaptations, but their roles
      are not well delineated, and that of the related stressor, dehydration, is
      largely unknown. While severe and prolonged hypohydration potentially "silences"
      the long-term heat acclimated phenotype, mild and transient dehydration may
      enhance cardiovascular and fluid-regulatory adaptations. We tested the hypothesis
      that exogenous heat stress and dehydration additively potentiate acute (24 h)
      cardiovascular and hematological outcomes following exercise. In a randomized
      crossover study, 10 physically-active volunteers (mean +/- SD: 173 +/- 11 cm;
      72.1 +/- 11.5 kg; 24 +/- 3 year; 6 females) completed three trials of 90-min
      orthostatically-stressful calisthenics, in: (i) temperate conditions (22 degrees
      C, 50% rh, no airflow; CON); (ii) heat (40 degrees C, 60% rh) whilst euhydrated
      (HEAT), and (iii) heat with dehydration (no fluid ~16 h before and during
      exercise; HEAT+DEHY). Using linear mixed effects model analyses, core temperature
      (TCORE) rose 0.7 degrees C more in HEAT than CON (95% CL: [0.5, 0.9]; p < 0.001),
      and another 0.4 degrees C in HEAT+DEHY ([0.2, 0.5]; p < 0.001, vs. HEAT). Skin
      temperature also rose 1.2 degrees C more in HEAT than CON ([0.6, 1.8]; p <
      0.001), and similarly to HEAT+DEHY (p = 0.922 vs. HEAT). Peak heart rate was 40
      b.min-1 higher in HEAT than in CON ([28, 51]; p < 0.001), and another 15 b.min-1
      higher in HEAT+DEHY ([3, 27]; p = 0.011, vs. HEAT). Mean arterial pressure at 24
      h recovery was not consistently below baseline after CON or HEAT (p >= 0.452),
      but was reduced 4 +/- 1 mm Hg after HEAT+DEHY ([0, 8]; p = 0.020 vs. baseline).
      Plasma volume at 24 h after exercise increased in all trials; the 7% increase in
      HEAT was not reliably more than in CON (5%; p = 0.335), but was an additional 4%
      larger after HEAT+DEHY ([1, 8]; p = 0.005 vs. HEAT). Pooled-trial correlational
      analysis showed the rise in TCORE predicted the hypotension (r = -0.4) and plasma
      volume expansion (r = 0.6) at 24 h, with more hypotension reflecting more plasma
      expansion (r = -0.5). In conclusion, transient dehydration with heat potentiates
      short-term (24-h) hematological (hypervolemic) and cardiovascular (hypotensive)
      outcomes following calisthenics.

PMID- 29062283
TI  - PTH Reloaded: A New Evolutionary Perspective.
AB  - The parathyroid hormone (PTH) family is a group of structurally-related secreted
      peptides involved in bone mineral homeostasis and multitude of developmental
      processes in vertebrates. These peptides mediate actions through PTH receptors
      (PTHRs), which belong to the transmembrane G protein-coupled receptor group. To
      date, genes encoding for PTH and PTHR have only been identified in chordates,
      suggesting that this signaling pathway may be an evolutionary innovation of our
      phylum. In vertebrates, we found up to six PTH and three PTHR different paralogs,
      varying in number between mammals and teleost fishes due to the different rounds
      of whole-genome duplication and specific gene losses suffered between the two
      groups of animals. The diversification of the PTH gene family has been
      accompanied by both functional divergence and convergence, making sometimes
      difficult the comparison between PTH peptides of teleosts and mammals. Here, we
      review the roles of all Pth peptides in fishes, and based on the evolutionary
      history of PTH paralogs, we propose a new and simple nomenclature from PTH1 to
      PTH4. Moreover, the recent characterization of the Pth4 in zebrafish allows us to
      consider the prominent role of the brain-to-bone signaling pathway in the
      regulation of bone development and homeostasis. Finally, comparison between PTH
      peptides of fish and mammals allows us to discuss an evolutionary model for PTH
      functions related to bone mineral balance during the vertebrate transition from
      an aquatic to a terrestrial environment.

PMID- 29062284
TI  - Does the Running Economy Really Increase after Ultra-Marathons?

PMID- 29062285
TI  - Perceived Social Change, Parental Control, and Family Relations: A Comparison of
      Chinese Families in Hong Kong, Mainland China, and the United States.
AB  - This study examined the relationship between perceived social change, parental
      control and family relations in a sample of 419 4th and 5th grade children and
      their mothers who are of Chinese descent but reside in three different contexts:
      Los Angeles (LA), Hong Kong (HK), and Beijing (BJ). HK mothers endorsed the
      highest levels of psychological control and the lowest levels of autonomy support
      compared to BJ and LA mothers. Perceived social change as measured by mothers'
      endorsement of new values and ideologies was associated with increased use of
      both autonomy support and psychological control. Results of the mediation
      analyses suggested that perceived social change explained differences between LA
      and HK mothers in autonomy support, but group differences in psychological
      control were magnified when perceived social change was accounted for. Finally,
      whereas autonomy support was associated with higher levels of child perceived
      acceptance in HK and LA, psychological control was associated with greater family
      conflict in BJ and LA. Findings suggested that as families undergo urbanization
      or social change, it may shift the implications of traditional strategies that
      are intended to socialize the child toward interpersonal attunement. Overall, the
      study highlights the importance of moving beyond ethnic-group or cross-national
      comparisons to investigate the role of changing social and economic contexts in
      understanding differences in the use of parental control and their associations
      with family relations.

PMID- 29062282
TI  - Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary
      Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib.
AB  - IL-6 is a central mediator of the immediate induction of hepatic acute phase
      proteins (APP) in the liver during infection and after injury, but increased IL-6
      activity has been associated with multiple pathological conditions. In
      hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative
      feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL
      6-induced JAK1-STAT3-signaling have been developed, understanding their precise
      impact on signaling dynamics requires a systems biology approach. Here we present
      a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively
      links physiological IL-6 concentrations to the dynamics of IL-6-induced signal
      transduction and expression of target genes in hepatocytes. The mathematical
      model consists of coupled ordinary differential equations (ODE) and the model
      parameters were estimated by a maximum likelihood approach, whereas
      identifiability of the dynamic model parameters was ensured by the Profile
      Likelihood. Using model simulations coupled with experimental validation we could
      optimize the long-term impact of the JAK-inhibitor Ruxolitinib, a therapeutic
      compound that is quickly metabolized. Model-predicted doses and timing of
      treatments helps to improve the reduction of inflammatory APP gene expression in
      primary mouse hepatocytes close to levels observed during regenerative
      conditions. The concept of improved efficacy of the inhibitor through multiple
      treatments at optimized time intervals was confirmed in primary human
      hepatocytes. Thus, combining quantitative data generation with mathematical
      modeling suggests that repetitive treatment with Ruxolitinib is required to
      effectively target excessive inflammatory responses without exceeding doses
      recommended by the clinical guidelines.

PMID- 29062286
TI  - The IARA Model as an Integrative Approach to Promote Autonomy in COPD Patients
      through Improvement of Self-Efficacy Beliefs and Illness Perception: A Mixed
      Method Pilot Study.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the most deadly and costly
      chronic diseases in the world characterized by many breathing problems. The
      management of COPD and the prevention of exacerbations are a priority goals to
      improve the quality of life in patients affected by this illness. In addition, it
      is also crucial to improve the patients' adherence to care which, in turn,
      depends on their knowledge and understanding of some factors such as the
      prescribed medical treatment, changes in dailylife, and the process of breathing.
      In turn, the adherence to care leads to greater autonomy for the patient who is
      thus able to better manage his illness. Here we presented the application of the
      Model IARA in patients affected by COPD in order to achieve their autonomy in
      illness management which, in turn, leads to a better quality of life. IARA is an
      intervention program which improve the awareness and knowledge of patients with
      respect to both the disease and symptoms through health education. Moreover,
      through IARA the patients are encouraged to become more actively involved in COPD
      care process, also regarding drug therapy adherence. Using St. George's
      Respiratory Questionnaire combined with qualitative analysis, we demonstrated
      that IARA could be considered a useful approach in COPD management.

PMID- 29062288
TI  - Perception of Risk and Terrorism-Related Behavior Change: Dual Influences of
      Probabilistic Reasoning and Reality Testing.
AB  - The present study assessed the degree to which probabilistic reasoning
      performance and thinking style influenced perception of risk and self-reported
      levels of terrorism-related behavior change. A sample of 263 respondents,
      recruited via convenience sampling, completed a series of measures comprising
      probabilistic reasoning tasks (perception of randomness, base rate, probability,
      and conjunction fallacy), the Reality Testing subscale of the Inventory of
      Personality Organization (IPO-RT), the Domain-Specific Risk-Taking Scale, and a
      terrorism-related behavior change scale. Structural equation modeling examined
      three progressive models. Firstly, the Independence Model assumed that
      probabilistic reasoning, perception of risk and reality testing independently
      predicted terrorism-related behavior change. Secondly, the Mediation Model
      supposed that probabilistic reasoning and reality testing correlated, and
      indirectly predicted terrorism-related behavior change through perception of
      risk. Lastly, the Dual-Influence Model proposed that probabilistic reasoning
      indirectly predicted terrorism-related behavior change via perception of risk,
      independent of reality testing. Results indicated that performance on
      probabilistic reasoning tasks most strongly predicted perception of risk, and
      preference for an intuitive thinking style (measured by the IPO-RT) best
      explained terrorism-related behavior change. The combination of perception of
      risk with probabilistic reasoning ability in the Dual-Influence Model enhanced
      the predictive power of the analytical-rational route, with conjunction fallacy
      having a significant indirect effect on terrorism-related behavior change via
      perception of risk. The Dual-Influence Model possessed superior fit and reported
      similar predictive relations between intuitive-experiential and analytical
      rational routes and terrorism-related behavior change. The discussion critically
      examines these findings in relation to dual-processing frameworks. This includes
      considering the limitations of current operationalisations and recommendations
      for future research that align outcomes and subsequent work more closely to
      specific dual-process models.

PMID- 29062287
TI  - Make Gestures to Learn: Reproducing Gestures Improves the Learning of Anatomical
      Knowledge More than Just Seeing Gestures.
AB  - Manual gestures can facilitate problem solving but also language or conceptual
      learning. Both seeing and making the gestures during learning seem to be
      beneficial. However, the stronger activation of the motor system in the second
      case should provide supplementary cues to consolidate and re-enact the mental
      traces created during learning. We tested this hypothesis in the context of
      anatomy learning by naive adult participants. Anatomy is a challenging topic to
      learn and is of specific interest for research on embodied learning, as the
      learning content can be directly linked to learners' body. Two groups of
      participants were asked to look at a video lecture on the forearm anatomy. The
      video included a model making gestures related to the content of the lecture.
      Both groups see the gestures but only one also imitate the model. Tests of
      knowledge were run just after learning and few days later. The results revealed
      that imitating gestures improves the recall of structures names and their
      localization on a diagram. This effect was however significant only in long-term
      assessments. This suggests that: (1) the integration of motor actions and
      knowledge may require sleep; (2) a specific activation of the motor system during
      learning may improve the consolidation and/or the retrieval of memories.

PMID- 29062289
TI  - Open-Minded Midwifes, Literate Butchers, and Greedy Hooligans-The Independent
      Contributions of Stereotype Valence and Consistency on Evaluative Judgments.
AB  - Do people evaluate an open-minded midwife less positively than a caring midwife?
      Both open-minded and caring are generally seen as positive attributes. However,
      consistency varies-the attribute caring is consistent with the midwife stereotype
      while open-minded is not. In general, both stimulus valence and consistency can
      influence evaluations. Six experiments investigated the respective influence of
      valence and consistency on evaluative judgments in the domain of stereotyping. In
      an impression formation paradigm, valence and consistency of stereotypic
      information about target persons were manipulated orthogonally and spontaneous
      evaluations of these target persons were measured. Valence reliably influenced
      evaluations. However, for strongly valenced stereotypes, no effect of consistency
      was observed. Parameters possibly preventing the occurrence of consistency
      effects were ruled out, specifically, valence of inconsistent attributes,
      processing priority of category information, and impression formation
      instructions. However, consistency had subtle effects on evaluative judgments if
      the information about a target person was not strongly valenced and experimental
      conditions were optimal. Concluding, in principle, both stereotype valence and
      consistency can play a role in evaluative judgments of stereotypic target
      persons. However, the more subtle influence of consistency does not seem to
      substantially influence evaluations of stereotyped target persons. Implications
      for fluency research and stereotype disconfirmation are discussed.

PMID- 29062290
TI  - Parental and Infant Gender Factors in Parent-Infant Interaction: State-Space
      Dynamic Analysis.
AB  - This study aimed to investigate the influence of parental gender on their
      interaction with their infants, considering, as well, the role of the infant's
      gender. The State Space Grid (SSG) method, a graphical tool based on the non
      linear dynamic system (NDS) approach was used to analyze the interaction, in Free
      Play setting, of 52 infants, aged 6 to 10 months, divided into two groups: half
      of the infants interacted with their fathers and half with their mothers. There
      were 50% boys in each group. MANOVA results showed no differential parenting of
      boys and girls. Additionally, mothers and fathers showed no differences in the
      Diversity of behavioral dyadic states nor in Predictability. However, differences
      associated with parent's gender were found in that the paternal dyads were more
      "active" than the maternal dyads: they were faster in the rates per second of
      behavioral events and transitions or change of state. In contrast, maternal dyads
      were more repetitive because, once they visited a certain dyadic state, they tend
      to be involved in more events. Results showed a significant discriminant function
      on the parental groups, fathers and mothers. Specifically, the content analyses
      carried out for the three NDS variables, that previously showed differences
      between groups, showed particular dyadic behavioral states associated with the
      rate of Transitions and the Events per Visit ratio. Thus, the transitions
      involving 'in-out' of 'Child Social Approach neutral - Sensitive Approach
      neutral' state and the repetitions of events in the dyadic state 'Child Play
      Sensitive Approach neutral' distinguished fathers from mothers. The
      classification of dyads (with fathers and mothers) based on this discriminant
      function identified 73.10% (19/26) of the father-infant dyads and 88.5% (23/26)
      of the mother-infant dyads. The study of father-infant interaction using the SSG
      approach offers interesting possibilities because it characterizes and quantifies
      the actual moment-to-moment flow of parent-infant interactive dynamics. Our
      findings showed how observational methods applied to natural contexts offer new
      facets in father vs. mother interactive behavior with their infants that can
      inform further developments in this field.

PMID- 29062291
TI  - Deep Convolutional Neural Networks Outperform Feature-Based But Not Categorical
      Models in Explaining Object Similarity Judgments.
AB  - Recent advances in Deep convolutional Neural Networks (DNNs) have enabled
      unprecedentedly accurate computational models of brain representations, and
      present an exciting opportunity to model diverse cognitive functions. State-of
      the-art DNNs achieve human-level performance on object categorisation, but it is
      unclear how well they capture human behavior on complex cognitive tasks. Recent
      reports suggest that DNNs can explain significant variance in one such task,
      judging object similarity. Here, we extend these findings by replicating them for
      a rich set of object images, comparing performance across layers within two DNNs
      of different depths, and examining how the DNNs' performance compares to that of
      non-computational "conceptual" models. Human observers performed similarity
      judgments for a set of 92 images of real-world objects. Representations of the
      same images were obtained in each of the layers of two DNNs of different depths
      (8-layer AlexNet and 16-layer VGG-16). To create conceptual models, other human
      observers generated visual-feature labels (e.g., "eye") and category labels
      (e.g., "animal") for the same image set. Feature labels were divided into parts,
      colors, textures and contours, while category labels were divided into
      subordinate, basic, and superordinate categories. We fitted models derived from
      the features, categories, and from each layer of each DNN to the similarity
      judgments, using representational similarity analysis to evaluate model
      performance. In both DNNs, similarity within the last layer explains most of the
      explainable variance in human similarity judgments. The last layer outperforms
      almost all feature-based models. Late and mid-level layers outperform some but
      not all feature-based models. Importantly, categorical models predict similarity
      judgments significantly better than any DNN layer. Our results provide further
      evidence for commonalities between DNNs and brain representations. Models derived
      from visual features other than object parts perform relatively poorly, perhaps
      because DNNs more comprehensively capture the colors, textures and contours which
      matter to human object perception. However, categorical models outperform DNNs,
      suggesting that further work may be needed to bring high-level semantic
      representations in DNNs closer to those extracted by humans. Modern DNNs explain
      similarity judgments remarkably well considering they were not trained on this
      task, and are promising models for many aspects of human cognition.

PMID- 29062292
TI  - But Is It really Art? The Classification of Images as "Art"/"Not Art" and
      Correlation with Appraisal and Viewer Interpersonal Differences.
AB  - When an individual participates in empirical studies involving the visual arts,
      they most often are presented with a stream of images, shown on a computer,
      depicting reproductions of artworks by respected artists but which are often not
      known to the viewer. While art can of course be shown in presentia actuale-e.g.,
      in the museum-this laboratory paradigm has become our go-to basis for assessing
      interaction, and, often in conjunction with some means of rating, for assessing
      evaluative, emotional, cognitive, and even neurophysiological response. However,
      the question is rarely asked: Do participants actually believe that every image
      that they are viewing is indeed "Art"? Relatedly, how does this evaluation relate
      to aesthetic appreciation, and do the answers to these questions vary in
      accordance with different strategies and interpersonal differences? In this
      paper, we consider the spontaneous classification of digital reproductions as art
      or not art. Participants viewed a range of image types-Abstract, Hyperrealistic,
      Poorly Executed paintings, Readymade sculptures, as well as Renaissance and
      Baroque paintings. They classified these as "art" or "not art" using both binary
      and analog scales, and also assessed for liking. Almost universally, individuals
      did not find all items within a class to be "art," nor did all participants agree
      on the arthood status for any one item. Art classification in turn showed a
      significant positive correlation with liking. Whether an object was classified as
      art moreover correlated with specific personality variables, tastes, and decision
      strategies. The impact of these findings is discussed for selection/assessment of
      participants and for better understanding the basis of findings in past and
      future empirical art research.

PMID- 29062294
TI  - When and How Does Psychological Voice Climate Influence Individual Change
      Readiness? The Mediating Role of Normative Commitment and the Moderating Role of
      Work Engagement.
AB  - This research explores the linking mechanisms and conditional processes
      underlying the relationship between psychological voice climate and individual
      change readiness. In accordance with the social identity theory, we argued that
      normative commitment would mediate the relationship between psychological voice
      climate and individual change readiness; furthermore, work engagement would
      moderate the proposed indirect effect. Two-wave survey data were collected from
      187 full-time employees in a government-owned institute of research and
      development and were adopted for moderated mediation analysis. The results showed
      that normative commitment mediates the relationship between psychological voice
      climate and individual change readiness. Furthermore, work engagement strengthens
      the effect of psychological voice climate on individual change readiness in an
      indirect manner via normative commitment. Based on the findings, the theoretical
      implications and practical suggestions were discussed.

PMID- 29062293
TI  - Discrimination of Urban Spaces with Different Level of Restorativeness Based on
      the Original and on a Shorter Version of Hartig et al.'s Perceived
      Restorativeness Scale.
AB  - Restorativeness is defined as the potential of the environment to re-establish
      certain cognitive capacities related to human information processing. The most
      frequently used instrument for evaluating the restorativeness of places is the
      Perceived Restorativeness Scale, proposed by Hartig et al. (1991). Later on,
      shorter versions of the Perceived Restorativeness Scale were proposed. The aim of
      this work is to evaluate the discriminatory capacity of the original and of a
      shorter Spanish version of the PRS, considering urban settings previously
      selected for having different level of restorativeness, according to expert's
      criteria. The study involved 244 students and used a 3 * 2 mixed experimental
      design, with two independent variables: Restorativeness of a place (between
      subjects), which was manipulated by showing pictures of settings selected with
      varying levels of restorativeness (high, medium, low), and length of the scale
      (within-subjects), which was manipulated by asking subjects to fill in both the
      original and a shorter version of the PRS. The order of presentation of the two
      scales was counterbalanced. Results show an appropriate reliability for both
      version of the scale. Items of being-away, fascination, and coherence of the
      shorter scale correlate more strongly with the corresponding factor of the
      original scale, compared to the others factors. Both scales produce similar
      values for the perceived restorativeness of the different places, except for
      places with low restorativeness.

PMID- 29062295
TI  - Familiar Tonal Context Improves Accuracy of Pitch Interval Perception.
AB  - A fundamental feature of everyday music perception is sensitivity to familiar
      tonal structures such as musical keys. Many studies have suggested that a tonal
      context can enhance the perception and representation of pitch. Most of these
      studies have measured response time, which may reflect expectancy as opposed to
      perceptual accuracy. We instead used a performance-based measure, comparing
      participants' ability to discriminate between a "small, in-tune" interval and a
      "large, mistuned" interval in conditions that involved familiar tonal relations
      (diatonic, or major, scale notes), unfamiliar tonal relations (whole-tone or
      mistuned-diatonic scale notes), repetition of a single pitch, or no tonal
      context. The context was established with a brief sequence of tones in Experiment
      1 (melodic context), and a cadence-like two-chord progression in Experiment 2
      (harmonic context). In both experiments, performance significantly differed
      across the context conditions, with a diatonic context providing a significant
      advantage over no context; however, no correlation with years of musical training
      was observed. The diatonic tonal context also provided an advantage over the
      whole-tone scale context condition in Experiment 1 (melodic context), and over
      the mistuned scale or repetition context conditions in Experiment 2 (harmonic
      context). However, the relatively small benefit to performance suggests that the
      main advantage of tonal context may be priming of expected stimuli, rather than
      enhanced accuracy of pitch interval representation.

PMID- 29062296
TI  - A Social-Ecological Framework of Theory, Assessment, and Prevention of Suicide.
AB  - The juxtaposition of increasing suicide rates with continued calls for suicide
      prevention efforts begs for new approaches. Grounded in the Centers for Disease
      Control and Prevention (CDC) framework for tackling health issues, this personal
      views work integrates relevant suicide risk/protective factor, assessment, and
      intervention/prevention literatures. Based on these components of suicide risk,
      we articulate a Social-Ecological Suicide Prevention Model (SESPM) which provides
      an integration of general and population-specific risk and protective factors. We
      also use this multi-level perspective to provide a structured approach to
      understanding current theories and intervention/prevention efforts concerning
      suicide. Following similar multi-level prevention efforts in interpersonal
      violence and Human Immunodeficiency Virus (HIV) domains, we offer recommendations
      for social-ecologically informed suicide prevention theory, training, research,
      assessment, and intervention programming. Although the SESPM calls for further
      empirical testing, it provides a suitable backdrop for tailoring of current
      prevention and intervention programs to population-specific needs. Moreover, the
      multi-level model shows promise to move suicide risk assessment forward (e.g.,
      development of multi-level suicide risk algorithms or structured professional
      judgments instruments) to overcome current limitations in the field. Finally, we
      articulate a set of characteristics of social-ecologically based suicide
      prevention programs. These include the need to address risk and protective
      factors with the strongest degree of empirical support at each multi-level layer,
      incorporate a comprehensive program evaluation strategy, and use a variety of
      prevention techniques across levels of prevention.

PMID- 29062297
TI  - Alexithymia Components Are Differentially Related to Explicit Negative Affect But
      Not Associated with Explicit Positive Affect or Implicit Affectivity.
AB  - Alexithymia represents a multifaceted personality construct defined by
      difficulties in recognizing and verbalizing emotions and externally oriented
      thinking. According to clinical observations, experience of negative affects is
      exacerbated and experience of positive affects is decreased in alexithymia.
      Findings from research based on self-report indicate that all alexithymia facets
      are negatively associated with the experience of positive affects, whereas
      difficulties identifying and describing feelings are related to heightened
      negative affect. Implicit affectivity, which can be measured using indirect
      assessment methods, relates to processes of the impulsive system. The aim of the
      present study was to examine, for the first time, the relations between
      alexithymia components and implicit and explicit positive and negative
      affectivity in healthy adults. The 20-item Toronto Alexithymia Scale, the
      Implicit Positive and Negative Affect Test and the Positive and Negative Affect
      Schedule (PANAS) were administered to two hundred and forty-one healthy
      individuals along with measures of depression and trait anxiety. Difficulties
      identifying feelings were correlated with explicit negative trait affect,
      depressive mood and trait anxiety. Difficulties describing feelings showed
      smaller but also significant correlations with depressive mood and trait anxiety
      but were not correlated with explicit state or trait affect as assessed by the
      PANAS. Externally oriented thinking was not significantly correlated with any of
      the implicit and explicit affect measures. According to our findings, an
      externally oriented, concrete way of thinking appears to be generally unrelated
      to dispositions to develop positive or negative affects. Difficulties identifying
      feelings seem to be associated with increased conscious negative affects but not
      with a heightened disposition to develop negative affects at an automatic
      response level.

PMID- 29062298
TI  - Commentary: Preliminary evaluation of an analog procedure to assess acceptability
      of intimate partner violence against women: the Partner Violence Acceptability
      Movie Task.

PMID- 29062299
TI  - Establishing the Substantive Interpretation of the GFP by Considering Evidence
      from Research on Personality Disorders and Animal Personality.

PMID- 29062300
TI  - Developing Emotional Design: Emotions as Cognitive Processes and their Role in
      the Design of Interactive Technologies.

PMID- 29062301
TI  - Curcumin Exerts Effects on the Pathophysiology of Alzheimer's Disease by
      Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression.
AB  - BACKGROUND: To validate our speculation that curcumin may ameliorate Alzheimer's
      disease (AD) pathogenesis by regulating PI(3,5)P2 and transient receptor
      potential mucolipin-1 (TRPML1) expression levels. METHODS: We developed an animal
      model presenting AD by APP/PS1 transgenes. The mouse clonal hippocampal neuronal
      cell line HT-22 was treated with amyloid-beta1-42 (Abeta1-42). Curcumin was
      administrated both in vivo and in vitro. MTS assay was used to detect cell
      viability, and the lysosomal [Ca2+] ion concentration was detected. The number of
      autophagosomes was detected by the transmission electron microscopic examination.
      Illumina RNA-seq was used to analyze the different expression patterns between
      Abeta1-42-treated cells without and with curcumin treatment. The protein level
      was analyzed by the Western blotting analysis. PI(3,5)P2 or TRPML1 was knocked
      down in HT-22 cells or in APP/PS1 transgenic mice. Morris water maze and
      recognition task were performed to trace the cognitive ability. RESULTS: Curcumin
      increased cell viability, decreased the number of autophagosomes, and increased
      lysosomal Ca2+ levels in Abeta1-42-treated HT-22 cells. Sequencing analysis
      identified TRPLML1 as the most significantly upregulated gene after curcumin
      treatment. Western blotting results also showed that TRPML1 was upregulated and
      mTOR/S6K signaling pathway was activated and markers of the autophagy-lysosomal
      system were downregulated after curcumin use in Abeta1-42-treated HT-22 cells.
      Knockdown of PI (3,5)P2 or TRPML1 increased the protein levels of markers of the
      autophagy-lysosomal system after curcumin use in Abeta1-42-treated HT-22 cells,
      inhibited mTOR/S6K signaling pathway, increased the protein levels of markers of
      the autophagy-lysosomal system after curcumin use in APP/PS1 mice. Besides,
      knockdown of PI(3,5)P2 or TRPML1 reversed the protective role of curcumin on
      memory and recognition impairments in mice with APP/PS1 transgenes. CONCLUSION:
      To some extent, it suggested that the effects of curcumin on AD pathogenesis
      were, at least partially, associated with PI(3,5)P2 and TRPML1 expression levels.

PMID- 29062302
TI  - Genetic Background and Expression of the New qepA4 Gene Variant Recovered in
      Clinical TEM-1- and CMY-2-Producing Escherichia coli.
AB  - A new QepA4 variant was detected in an O86:H28 ST156-fimH38 Escherichia coli,
      showing a multidrug-resistance phenotype. PAbetaN inhibition of qepA4-harboring
      transconjugant resulted in increase of nalidixic acid accumulation. The qepA4 and
      catA1 genes were clustered in a 26.0-kp contig matching an IncF-type plasmid, and
      containing a Tn21-type transposon with multiple mobile genetic elements. This
      QepA variant is worrisome because these determinants might facilitate the
      selection of higher-level resistance mutants, playing a role in the development
      of resistance, and/or confer higher-level resistance to fluoroquinolones in
      association with chromosomal mutations.

PMID- 29062303
TI  - Exploring Fingerprints of the Extreme Thermoacidophile Metallosphaera sedula
      Grown on Synthetic Martian Regolith Materials as the Sole Energy Sources.
AB  - The biology of metal transforming microorganisms is of a fundamental and applied
      importance for our understanding of past and present biogeochemical processes on
      Earth and in the Universe. The extreme thermoacidophile Metallosphaera sedula is
      a metal mobilizing archaeon, which thrives in hot acid environments (optimal
      growth at 74 degrees C and pH 2.0) and utilizes energy from the oxidation of
      reduced metal inorganic sources. These characteristics of M. sedula make it an
      ideal organism to further our knowledge of the biogeochemical processes of
      possible life on extraterrestrial planetary bodies. Exploring the viability and
      metal extraction capacity of M. sedula living on and interacting with synthetic
      extraterrestrial minerals, we show that M. sedula utilizes metals trapped in the
      Martian regolith simulants (JSC Mars 1A; P-MRS; S-MRS; MRS07/52) as the sole
      energy sources. The obtained set of microbiological and mineralogical data
      suggests that M. sedula actively colonizes synthetic Martian regolith materials
      and releases free soluble metals. The surface of bioprocessed Martian regolith
      simulants is analyzed for specific mineralogical fingerprints left upon M. sedula
      growth. The obtained results provide insights of biomining of extraterrestrial
      material as well as of the detection of biosignatures implementing in life search
      missions.

PMID- 29062306
TI  - The PGPR Stenotrophomonas maltophilia SBP-9 Augments Resistance against Biotic
      and Abiotic Stress in Wheat Plants.
AB  - Certain plant growth promoting bacteria have ability to ameliorate abiotic and/or
      biotic stressors, which can be exploited to enhance plant growth and productivity
      of the plants under stress conditions. Therefore, the present study aimed to
      examine the role of a rhizospheric bacterial isolate SBP-9 isolated from Sorghum
      bicolor (i) in promoting the wheat plant growth under salinity stress, and (ii)
      in enhancing the defense response in wheat against fungal pathogen "Fusarium
      graminearum." The test isolate possessed plant growth promoting (PGP) traits
      including ACC deaminase (ACCD), gibberellic acid, indole acetic acid (IAA),
      siderophore, and inorganic phosphate solubilization. Under salt (NaCl) stress,
      inoculation of this isolate to wheat plant significantly increased plant growth
      in terms of various growth parameters such as shoot length/root length (20-39%),
      fresh weight/dry weight (28-42%), and chlorophyll content (24-56%) following
      inoculation of test isolate SBP-9. Bacterial inoculation decreased the level of
      proline, and malondialdehyde, whereas elevated the antioxidative enzymatic
      activities of superoxide-dismutase (SOD; 28-41%), catalase (CAT; 24-56%), and
      peroxidase (POX; 26-44%). Furthermore, it also significantly decreased the Na+
      accumulation in both shoot and roots in the range of 25-32%, and increased the K+
      uptake by 20-28%, thereby favoring the K+/Na+ ratio. On the other hand, the test
      isolate also enhanced the level of defense enzymes like beta-1, 3 glucanase,
      phenylalanine ammonia lyase (PAL), peroxidae (PO), and polyphenol oxidase (PPO),
      which can protect plants from the infection of pathogens. The result of
      colonization test showed an ability of the test isolate to successfully colonize
      the wheat plants. These results indicate that Stenotrophomonas maltophilia SBP-9
      has potential to promote the wheat growth under biotic and abiotic (salt)
      stressors directly or indirectly and can be further tested at field level for
      exploitation as bioinoculant.

PMID- 29062305
TI  - Morbid Sequences Suggest Molecular Mimicry between Microbial Peptides and Self
      Antigens: A Possibility of Inciting Autoimmunity.
AB  - Understanding etiology of autoimmune diseases has been a great challenge for
      designing drugs and vaccines. The pathophysiology of many autoimmune diseases may
      be attributed to molecular mimicry provoked by microbes. Molecular mimicry
      hypothesizes that a sequence homology between foreign and self-peptides leads to
      cross-activation of autoreactive T cells. Different microbial proteins are
      implicated in various autoimmune diseases, including multiple sclerosis, human
      type 1 diabetes, primary biliary cirrhosis and rheumatoid arthritis. It may be
      imperative to identify the microbial epitopes that initiate the activation of
      autoreactive T cells. Consequently, in the present study, we employed
      immunoinformatics tools to delineate homologous antigenic regions between
      microbes and human proteins at not only the sequence level but at the structural
      level too. Interestingly, many cross-reactive MHC class II binding epitopes were
      detected from an array of microbes. Further, these peptides possess a potential
      to skew immune response toward Th1-like patterns. The present study divulges many
      microbial target proteins, their putative MHC-binding epitopes, and predicted
      structures to establish the fact that both sequence and structure are two
      important aspects for understanding the relationship between molecular mimicry
      and autoimmune diseases. Such findings may enable us in designing potential
      immunotherapies to tolerize autoreactive T cells.

PMID- 29062304
TI  - Comparative Genomics of Sibling Species of Fonsecaea Associated with Human
      Chromoblastomycosis.
AB  - Fonsecaea and Cladophialophora are genera of black yeast-like fungi harboring
      agents of a mutilating implantation disease in humans, along with strictly
      environmental species. The current hypothesis suggests that those species reside
      in somewhat adverse microhabitats, and pathogenic siblings share virulence
      factors enabling survival in mammal tissue after coincidental inoculation driven
      by pathogenic adaptation. A comparative genomic analysis of environmental and
      pathogenic siblings of Fonsecaea and Cladophialophora was undertaken, including
      de novo assembly of F. erecta from plant material. The genome size of Fonsecaea
      species varied between 33.39 and 35.23 Mb, and the core genomes of those species
      comprises almost 70% of the genes. Expansions of protein domains such as
      glyoxalases and peptidases suggested ability for pathogenicity in clinical
      agents, while the use of nitrogen and degradation of phenolic compounds was
      enriched in environmental species. The similarity of carbohydrate-active vs.
      protein-degrading enzymes associated with the occurrence of virulence factors
      suggested a general tolerance to extreme conditions, which might explain the
      opportunistic tendency of Fonsecaea sibling species. Virulence was tested in the
      Galleria mellonella model and immunological assays were performed in order to
      support this hypothesis. Larvae infected by environmental F. erecta had a lower
      survival. Fungal macrophage murine co-culture showed that F. erecta induced high
      levels of TNF-alpha contributing to macrophage activation that could increase the
      ability to control intracellular fungal growth although hyphal death were not
      observed, suggesting a higher level of extremotolerance of environmental species.

PMID- 29062307
TI  - High Manganese Tolerance and Biooxidation Ability of Serratia marcescens Isolated
      from Manganese Mine Water in Minas Gerais, Brazil.
AB  - Manganese is an important metal for the maintenance of several biological
      functions, but it can be toxic in high concentrations. One of the main forms of
      human exposure to metals, such as manganese (Mn), is the consumption of solar
      salt contaminated. Mn-tolerant bacteria could be used to decrease the
      concentration of this metal from contaminated sites through safer environmental
      friendly alternative technology in the future. Therefore, this study was
      undertaken to isolate and identify Mn resistant bacteria from water samples
      collected from a Mn mine in the Iron Quadrangle region (Minas Gerais, Brazil).
      Two bacterial isolates were identified as Serratia marcescens based on
      morphological, biochemical, 16S rDNA gene sequencing and phylogeny analysis.
      Maximum resistance of the selected isolates against increasing concentrations of
      Mn(II), up to 1200 mg L-1 was determined in solid media. A batch assay was
      developed to analyze and quantify the Mn removal capacities of the isolates.
      Biological Mn removal capacities of over 55% were detected for both isolates.
      Whereas that mechanism like biosorption, precipitation and oxidation could be
      explaining the Mn removal, we seek to give an insight into some of the molecular
      mechanisms adopted by S. marcescens isolates. For this purpose, the following
      approaches were adopted: leucoberbelin blue I assay, Mn(II) oxidation by cell
      free filtrate and electron microscopy and energy-dispersive X-ray spectroscopy
      analyses. Overall, these results indicate that S. marcescens promotes Mn removal
      in an indirect mechanism by the formation of Mn oxides precipitates around the
      cells, which should be further explored for potential biotechnological
      applications for water recycling both in hydrometallurgical and mineral
      processing operations.

PMID- 29062308
TI  - Akkermansia muciniphila May Determine Chondroitin Sulfate Ameliorating or
      Aggravating Osteoarthritis.
AB  - Chondroitin sulfate (CS) has shown either ameliorating or aggravating effects on
      osteoarthritis (OA) in separately conducted clinical trials. Because CS is
      usually administered orally, it should be affected by or would impact on the
      individual gut microbiota. Evidence is accumulating that CS can nourish sulfatase
      secreting bacteria (SSB) and sulfate-reducing bacteria (SRB). To decipher how can
      an individual gut microbiota determine the clinical values of CS for treatment on
      OA, we suggest here that CS would give distinct outcomes for OA treatment
      depending on Akkermansia muciniphila, a gut commensal probiotic bacterial species
      as optimal presence albeit also behaving as mucus-eroding bacteria (MEB) when
      abundant presence. Briefly, CS would ameliorate OA if A. muciniphila is present
      due to without overgrowth of SSB and SRB, whereas CS would aggravate OA if A.
      muciniphila is absent because of failure in or lack of competition with abundant
      SSB and SRB. By noting such a frequently ignored phenomenon, we urge the
      development of non-orally administering CS to minimize its side-effects and
      extend it to other medicinal applications.

PMID- 29062309
TI  - pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal
      Pathogen Candida albicans.
AB  - Current antifungal drugs suffer from limitations including toxicity, the
      emergence of resistance and decreased efficacy at low pH that are typical of
      human vaginal surfaces. Here, we have shown that the antipsychotic drug valproic
      acid (VPA) exhibited a strong antifungal activity against both sensitive and
      resistant Candida albicans in pH condition similar to that encountered in vagina.
      VPA exerted a strong anti-biofilm activity and attenuated damage of vaginal
      epithelial cells caused by C. albicans. We also showed that VPA synergizes with
      the allylamine antifungal, Terbinafine. We undertook a chemogenetic screen to
      delineate biological processes that underlies VPA-sensitivity in C. albicans and
      found that vacuole-related genes were required to tolerate VPA. Confocal
      fluorescence live-cell imaging revealed that VPA alters vacuole integrity and
      support a model where alteration of vacuoles contributes to the antifungal
      activity. Taken together, this study suggests that VPA could be used as an
      effective antifungal against vulvovaginal candidiasis.

PMID- 29062310
TI  - Analysis of the Protective Immunity Induced by Herpes Simplex Virus 1 Strain M3
      with an Attenuated Phenotype Due to Mutations in the Viral ul7, ul41, and LAT
      Genes.
AB  - Herpes simplex virus 1 (HSV1) is an important pathogen with a worldwide epidemic
      trend that affects populations of various ages. It has a high morbidity,
      particularly in juveniles, but a successful HSV1 vaccine is not currently
      available. Thus, our study systematically observed the immune responses induced
      in mice immunized with the attenuated HSV1 M3 mutant strain, which has mutations
      in the genes encoding the UL7 and Vhs tegument proteins and the latency
      associated transcript. The immunity induced by the M3 mutant strain can control
      acute viral infection during HSV1 wild-type strain infection. Moreover, this
      immunity exerts a potent effect on controlling viral entry into the trigeminal
      neurons. These data encourage further studies investigating the development of M3
      as a potential vaccine candidate, and much work is necessary to evaluate the
      safety and improve the immunogenicity of this strain.

PMID- 29062311
TI  - Production of High Amounts of Hepatotoxin Nodularin and New Protease Inhibitors
      Pseudospumigins by the Brazilian Benthic Nostoc sp. CENA543.
AB  - Nostoc is a cyanobacterial genus, common in soils and a prolific producer of
      natural products. This research project aimed to explore and characterize
      Brazilian cyanobacteria for new bioactive compounds. Here we report the
      production of hepatotoxins and new protease inhibitors from benthic Nostoc sp.
      CENA543 isolated from a small, shallow, saline-alkaline lake in the Nhecolandia,
      Pantanal wetland area in Brazil. Nostoc sp. CENA543 produces exceptionally high
      amounts of nodularin-R. This is the first free-living Nostoc that produces
      nodularin at comparable levels as the toxic, bloom-forming, Nodularia spumigena.
      We also characterized pseudospumigins A-F, which are a novel family of linear
      tetrapeptides. Pseudospumigins are structurally related to linear tetrapeptide
      spumigins and aeruginosins both present in N. spumigena but differ in respect to
      their diagnostic amino acid, which is Ile/Leu/Val in pseudospumigins, Pro/mPro in
      spumigins, and Choi in aeruginosins. The pseudospumigin gene cluster is more
      similar to the spumigin biosynthetic gene cluster than the aeruginosin gene
      cluster. Pseudospumigin A inhibited trypsin (IC50 4.5 MUM after 1 h) in a similar
      manner as spumigin E from N. spumigena but was almost two orders of magnitude
      less potent. This study identifies another location and environment where the
      hepatotoxic nodularin has the potential to cause the death of eukaryotic
      organisms.

PMID- 29062313
TI  - Dead Tumor Cells Expressing Infectious Salmon Anemia Virus Fusogenic Protein
      Favor Antigen Cross-Priming In Vitro.
AB  - Antigen cross-presentation is a crucial step in the assembly of an antitumor
      immune response leading to activation of naive CD8 T cells. This process has been
      extensively used in clinical trials, in which dendritic cells generated in vitro
      are loaded with tumor antigens and then autotransplanted to the patients.
      Recently, the use of autologous transplant of dendritic cells fused with dying
      tumor cells has demonstrated good results in clinical studies. In this work, we
      generated a similar process in vivo by treating mice with dead tumor cells [cell
      bodies (CBs)] expressing the fusogenic protein of the infectious salmon anemia
      virus (ISAV). ISAV fusion protein retains its fusogenic capability when is
      expressed on mammalian cells in vitro and the CBs expressing it facilitates DCs
      maturation, antigen transfer by antigen-presenting cells, and increase cross
      presentation by DCs in vitro. Additionally, we observed in the melanoma model
      that CBs with or without ISAV fusion protein reduce tumor growth in prophylactic
      treatment; however, only ISAV expressing CBs showed an increase CD4 and CD8 cells
      in spleen. Overall, our results suggest that CBs could be used as a complement
      with other type of strategies to amplify antitumor immune response.

PMID- 29062312
TI  - Plasmid-Mediated Bioaugmentation for the Bioremediation of Contaminated Soils.
AB  - Bioaugmentation, or the inoculation of microorganisms (e.g., bacteria harboring
      the required catabolic genes) into soil to enhance the rate of contaminant
      degradation, has great potential for the bioremediation of soils contaminated
      with organic compounds. Regrettably, cell bioaugmentation frequently turns into
      an unsuccessful initiative, owing to the rapid decrease of bacterial viability
      and abundance after inoculation, as well as the limited dispersal of the
      inoculated bacteria in the soil matrix. Genes that encode the degradation of
      organic compounds are often located on plasmids and, consequently, they can be
      spread by horizontal gene transfer into well-established, ecologically
      competitive, indigenous bacterial populations. Plasmid-mediated bioaugmentation
      aims to stimulate the spread of contaminant degradation genes among indigenous
      soil bacteria by the introduction of plasmids, located in donor cells, harboring
      such genes. But the acquisition of plasmids by recipient cells can affect the
      host's fitness, a crucial aspect for the success of plasmid-mediated
      bioaugmentation. Besides, environmental factors (e.g., soil moisture,
      temperature, organic matter content) can play important roles for the transfer
      efficiency of catabolic plasmids, the expression of horizontally acquired genes
      and, finally, the contaminant degradation activity. For plasmid-mediated
      bioaugmentation to be reproducible, much more research is needed for a better
      selection of donor bacterial strains and accompanying plasmids, together with an
      in-depth understanding of indigenous soil bacterial populations and the
      environmental conditions that affect plasmid acquisition and the expression and
      functioning of the catabolic genes of interest.

PMID- 29062315
TI  - Dual-Specificity Phosphatase 12 Targets p38 MAP Kinase to Regulate Macrophage
      Response to Intracellular Bacterial Infection.
AB  - The mitogen-activated protein kinase (MAPK) cascades are activated in innate
      immune cells such as macrophages upon the detection of microbial infection,
      critically regulating the expression of proinflammatory cytokines and chemokines
      such as TNF-alpha, IL-6, and MCP-1. As a result, activation of MAPKs is tightly
      regulated to ensure appropriate and adequate immune responses. Dual-specificity
      phosphatases (DUSPs) are a family of proteins which specifically dephosphorylates
      threonine and tyrosine residues essential for MAPK activation to negatively
      regulate their activation. DUSP12 is a member of atypical DUSPs that lack MAPK
      binding domain. Its substrate and function in immune cells are unknown. In this
      study, we demonstrated that DUSP12 is able to interact with all the three groups
      of MAPKs, including extracellular signal-regulated protein kinase, JNK, and p38.
      To investigate the function of DUSP12 in macrophages in response to TLR
      activation and microbial infection, we established RAW264.7 cell lines stably
      overexpressing DUSP12 and found that overexpression of DUSP12 inhibited
      proinflammatory cytokine and chemokine production in response to TLR4 activation,
      heat-inactivated Mycobacterium tuberculosis stimulation as well as infections by
      intracellular bacteria including Listeria moncytogenesis and Mycobacterium bovis
      BCG by specifically inhibiting p38 and JNK. In addition, a scaffold protein known
      as signal transducing adaptor protein 2 (STAP2), was found to mediate the
      interaction between DUSP12 and p38. Thus, DUSP12 is a bona fide MAPK phosphatase,
      playing an important role in MAPK-regulated responses to bacterial infection. Our
      study provides a model where atypical DUSPs regulate MAPKs via scaffold, thereby
      regulating immune responses to microbial infection.

PMID- 29062314
TI  - Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis.
AB  - Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic
      cell clearance during homeostasis has been shown to limit subsequent immune
      responses. Based on these observations, early-stage apoptotic cell infusion has
      been used to prevent unwanted inflammatory responses in different experimental
      models of autoimmune diseases or transplantation. Moreover, this approach has
      been shown to be feasible without any toxicity in patients undergoing allogeneic
      hematopoietic cell transplantation to prevent graft-versus-host disease. However,
      whether early-stage apoptotic cell infusion can be used to treat ongoing
      inflammatory disorders has not been reported extensively. Recently, we have
      provided evidence that early-stage apoptotic cell infusion is able to control, at
      least transiently, ongoing collagen-induced arthritis. This beneficial
      therapeutic effect is associated with the modulation of antigen-presenting cell
      functions mainly of macrophages and plasmacytoid dendritic cells, as well as the
      induction of collagen-specific regulatory CD4+ T cells (Treg). Furthermore, the
      efficacy of this approach is not altered by the association with two standard
      treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor
      (TNF) inhibition. Here, in the light of these observations and recent data of the
      literature, we discuss the mechanisms of early-stage apoptotic cell infusion and
      how this therapeutic approach can be transposed to patients with RA.

PMID- 29062316
TI  - Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases.
AB  - Prematurity affects approximately 10% of all children, resulting in drastically
      altered antigen exposure due to premature confrontation with microbes,
      nutritional antigens, and other environmental factors. During the last trimester
      of pregnancy, the fetal immune system adapts to tolerate maternal and self
      antigens, while also preparing for postnatal immune defense by acquiring passive
      immunity from the mother. Since the perinatal period is regarded as the most
      important "window of opportunity" for imprinting metabolism and immunity, preterm
      birth may have long-term consequences for the development of immune-mediated
      diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more
      frequently, but atopic dermatitis less frequently in comparison to term neonates.
      The longitudinal study of preterm neonates could offer important insights into
      the process of imprinting for immune-mediated diseases. On the one hand, preterm
      birth may interrupt influences of the intrauterine environment on the fetus that
      increase or decrease the risk of later immune disease (e.g., maternal antibodies
      and placenta-derived factors), whereas on the other hand, it may lead to the
      premature exposure to protective or harmful extrauterine factors such as
      microbiota and nutritional antigen. Solving this puzzle may help unravel new
      preventive and therapeutic approaches for immune diseases.

PMID- 29062317
TI  - p40 phox -Deficient Mice Exhibit Impaired Bacterial Clearance and Enhanced Pro
      inflammatory Responses during Salmonella enterica serovar Typhimurium Infection.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of
      acute gastroenteritis in humans. During infection, reactive oxygen species (ROS),
      generated from NADPH oxidase (a multisubunit enzyme complex), are required for
      pathogen killing upon phagocytosis and for regulating pro-inflammatory signaling
      in phagocytic cells. Mutations in subunits forming the NADPH complex may lead to
      enhanced susceptibility to infection and inflammatory disease. Compared to other
      NADPH oxidase subunits, the function of p40 phox is relatively understudied,
      particularly in the context of intestinal bacterial infection. In this study, we
      utilized genetically engineered mice to determine the role of p40 phox in the
      response to S. Typhimurium infection. We show that mice lacking p40 phox are more
      susceptible to oral infection with S. Typhimurium, as demonstrated by
      significantly enhanced bacterial dissemination to spleen and liver, and
      development of exacerbated bacterial colitis. Moreover, we demonstrate that the
      increased infection and disease severity are correlated with markedly increased
      F4/80+ macrophage and Ly6G+ neutrophil infiltration in the infected tissues,
      coincident with significantly elevated pro-inflammatory cytokines (IL-1beta and
      TNF-alpha) and chemoattractant molecules in the infected tissues. Functional
      analysis of macrophages and neutrophils further shows that p40 phox deficiency
      impairs bacteria- or PMA-induced intracellular ROS production as well as
      intracellular killing of Salmonella. These observations indicate that the p40
      phox subunit of NADPH oxidase plays an essential role in suppressing
      intracellular multiplication of Salmonella in macrophages and in the regulation
      of both systemic and mucosal inflammatory responses to bacterial infection.

PMID- 29062319
TI  - A Biosensor-Based Leaf Punch Assay for Glutamine Correlates to Symbiotic Nitrogen
      Fixation Measurements in Legumes to Permit Rapid Screening of Rhizobia Inoculants
      under Controlled Conditions.
AB  - Legumes are protein sources for billions of humans and livestock. These traits
      are enabled by symbiotic nitrogen fixation (SNF), whereby root nodule-inhabiting
      rhizobia bacteria convert atmospheric nitrogen (N) into usable N. Unfortunately,
      SNF rates in legume crops suffer from undiagnosed incompatible/suboptimal
      interactions between crop varieties and rhizobia strains. There are opportunities
      to test much large numbers of rhizobia strains if cost/labor-effective diagnostic
      tests become available which may especially benefit researchers in developing
      countries. Inside root nodules, fixed N from rhizobia is assimilated into amino
      acids including glutamine (Gln) for export to shoots as the major fraction (amide
      exporting legumes) or as the minor fraction (ureide-exporting legumes). Here, we
      have developed a new leaf punch based technique to screen rhizobia inoculants for
      SNF activity following inoculation of both amide exporting and ureide exporting
      legumes. The assay is based on measuring Gln output using the GlnLux biosensor,
      which consists of Escherichia coli cells auxotrophic for Gln and expressing a
      constitutive lux operon. Subsistence farmer varieties of an amide exporter
      (lentil) and two ureide exporters (cowpea and soybean) were inoculated with
      different strains of rhizobia under controlled conditions, then extracts of
      single leaf punches were incubated with GlnLux cells, and light-output was
      measured using a 96-well luminometer. In the absence of external N and under
      controlled conditions, the results from the leaf punch assay correlated with 15N
      based measurements, shoot N percentage, and shoot total fixed N in all three
      crops. The technology is rapid, inexpensive, high-throughput, requires minimum
      technical expertise and very little tissue, and hence is relatively non
      destructive. We compared and contrasted the benefits and limitations of this
      novel diagnostic assay to methods.

PMID- 29062320
TI  - Description and Codification of Miscanthus * giganteus Growth Stages for
      Phenological Assessment.
AB  - Triploid Miscanthus * giganteus (Greef et Deu. ex Hodkinson et Renvoize) is a
      sterile, perennial grass used for biomass production in temperate environments.
      While M. * giganteus has been intensively researched, a scale standardizing
      description of M. * giganteus morphological stages has not been developed. Here
      we provide such a scale by adapting the widely-used Biologische Bundesanstalt,
      Bundessortenamt, CHemische Industrie (BBCH) scale and its corresponding numerical
      code to describe stages of morphological development in M. * giganteus using
      observations of the "Freedom" and "Illinois" clone in Iowa, USA. Descriptive keys
      with images are also presented. Because M. * giganteus plants overlap in the
      field, the scale was first applied to individual stems and then scaled up to
      assess plants or communities. Of the 10 principal growth stages in the BBCH
      system, eight were observed in M. * giganteus. Each principal stage was
      subdivided into secondary stages to enable a detailed description of
      developmental progression. While M. * giganteus does not have seed development
      stages, descriptions of those stages are provided to extend the scale to other
      Miscanthus genotypes. We present methods to use morphological development data to
      assess phenology by calculating the onset, duration, and abundance of each
      developmental stage. This scale has potential to harmonize previously described
      study-specific scales and standardize results across studies. Use of the precise
      staging presented here should more tightly constrain estimates of developmental
      parameters in crop models and increase the efficacy of timing-sensitive crop
      management practices like pest control and harvest.

PMID- 29062318
TI  - Evaluation of Recombinant Attenuated Salmonella Vaccine Strains for Broad
      Protection against Extraintestinal Pathogenic Escherichia coli.
AB  - Antibiotic-resistant bacterial infections are difficult to treat, producing a
      burden on healthcare and the economy. Extraintestinal pathogenic Escherichia coli
      (ExPEC) strains frequently carry antibiotic resistance genes, cause infections
      outside of the intestine, and are causative agents of hospital-acquired
      infections. Developing a prevention strategy against this pathogen is challenging
      due to its antibiotic resistance and antigenic diversity. E. coli common pilus
      (ECP) is frequently found in ExPEC strains and may serve as a common antigen to
      induce protection against several ExPEC serotypes. In addition, live recombinant
      attenuated Salmonella vaccine (RASV) strains have been used to prevent Salmonella
      infection and can also be modified to deliver foreign antigens. Thus, the
      objective of this study was to design a RASV to produce ECP on its surface and
      assess its ability to provide protection against ExPEC infections. To
      constitutively display ECP in a RASV strain, we genetically engineered a vector
      (pYA4428) containing aspartate-beta-semialdehyde dehydrogenase and E. coli ecp
      genes and introduced it into RASV chi9558. RASV chi9558 containing an empty
      vector (pYA3337) was used as a control to assess protection conferred by the RASV
      strain without ECP. We assessed vaccine efficacy in in vitro bacterial inhibition
      assays and mouse models of ExPEC-associated human infections. We found that RASV
      chi9558(pYA4428) synthesized the major pilin (EcpA) and tip pilus adhesin (EcpD)
      on the bacterial surface. Mice orally vaccinated with RASV chi9558(pYA3337)
      without ECP or chi9558(pYA4428) with ECP, produced anti-Salmonella LPS and anti
      E. coli EcpA and EcpD IgG and IgA antibodies. RASV strains showed protective
      potential against some E. coli and Salmonella strains as assessed using in vitro
      assays. In mouse sepsis and urinary tract infection challenge models, both
      vaccines had significant protection in some internal organs. Overall, this work
      showed that RASVs can elicit an immune response to E. coli and Salmonella
      antigens in some mice, provide significant protection in some internal organs
      during ExPEC challenge, and thus this study is a promising initial step toward
      developing a vaccine for prevention of ExPEC infections. Future studies should
      optimize the ExPEC antigens displayed by the RASV strain for a more robust immune
      response and enhanced protection against ExPEC infection.

PMID- 29062321
TI  - 50/50 Expressional Odds of Retention Signifies the Distinction between Retained
      Introns and Constitutively Spliced Introns in Arabidopsis thaliana.
AB  - Intron retention, one of the most prevalent alternative splicing events in
      plants, can lead to introns retained in mature mRNAs. However, in comparison with
      constitutively spliced introns (CSIs), the relevantly distinguishable features
      for retained introns (RIs) are still poorly understood. This work proposes a
      computational pipeline to discover novel RIs from multiple next-generation RNA
      sequencing (RNA-Seq) datasets of Arabidopsis thaliana. Using this pipeline, we
      detected 3,472 novel RIs from 18 RNA-Seq datasets and re-confirmed 1,384 RIs
      which are currently annotated in the TAIR10 database. We also use the expression
      of intron-containing isoforms as a new feature in addition to the conventional
      features. Based on these features, RIs are highly distinguishable from CSIs by
      machine learning methods, especially when the expressional odds of retention
      (i.e., the expression ratio of the RI-containing isoforms relative to the
      isoforms without RIs for the same gene) reaches to or larger than 50/50. In this
      case, the RIs and CSIs can be clearly separated by the Random Forest with an
      outstanding performance of 0.95 on AUC (the area under a receiver operating
      characteristics curve). The closely related characteristics to the RIs include
      the low strength of splice sites, high similarity with the flanking exon
      sequences, low occurrence percentage of YTRAY near the acceptor site, existence
      of putative intronic splicing silencers (ISSs, i.e., AG/GA-rich motifs) and
      intronic splicing enhancers (ISEs, i.e., TTTT-containing motifs), and enrichment
      of Serine/Arginine-Rich (SR) proteins and heterogeneous nuclear
      ribonucleoparticle proteins (hnRNPs).

PMID- 29062322
TI  - Whole Gene Deletion of EBF3 Supporting Haploinsufficiency of This Gene as a
      Mechanism of Neurodevelopmental Disease.
AB  - Mutations in early B cell factor 3 (EBF3) were recently described in patients
      with a neurodevelopmental disorder (NDD) that includes developmental
      delay/intellectual disability, ataxia, hypotonia, speech impairment, strabismus,
      genitourinary abnormalities, and mild facial dysmorphisms. Several large 10q
      terminal and interstitial deletions affecting many genes and including EBF3 have
      been described in the literature. However, small deletions (<1 MB) affecting
      almost exclusively EBF3 are not commonly reported. We performed array comparative
      genomic hybridization (aCGH) (Agilent 180K) and quantitative PCR analysis in a
      female patient with intellectual disability. A clinical comparison between our
      patient and overlapping cases reported in the literature was also made. The
      patient carries a de novo 600 Kb deletion at 10q26.3 affecting the MGMT, EBF3,
      and GLRX genes. The patient has severe intellectual disability, language
      impairment, conductive hearing loss, hypotonia, vision alterations, triangular
      face, short stature, and behavior problems. This presentation overlaps that
      reported for patients carrying EBF3 heterozygous point mutations, as well as
      literature reports of patients carrying large 10qter deletions. Our results and
      the literature review suggest that EBF3 haploinsufficiency is a key contributor
      to the common aspects of the phenotype presented by patients bearing point
      mutations and indels in this gene, given that deletions affecting the entire gene
      (alone or in addition to other genes) are causative of a similar syndrome,
      including intellectual disability (ID) with associated neurological symptoms and
      particular facial dysmorphisms.

PMID- 29062323
TI  - The burden, pattern and factors that contribute to periportal fibrosis in HIV
      infected patients in an S. mansoni endemic rural Uganda.
AB  - INTRODUCTION: Both Human Immunodeficiency Virus (HIV) and S.mansoni infections
      are common in Uganda and can cause liver disease. No study has determined co
      infection significance in Uganda. We carried out a study on the burden, pattern
      and factors that contribute to peri-portal fibrosis (PPF) in HIV infected
      patients attending a Primary healthcare setting at Pakwach. METHODOLOGY: We
      conducted a cross-sectional study in the HIV clinic at Pakwach health centre IV.
      Data on demographics, contact with the Nile, CD4+ cell count, ART and alcohol use
      were collected. Urinary Circulating Cathodic Antigen (CCA), was done for S.
      Mansoni detection. Liver scan was done for presence and pattern of PPF. HBsAg
      testing was performed on all participants. Data was analyzed using Stata Version
      10. RESULTS: We enrolled 299 patients, median age 39 years (IQR 16), most were
      female, 210 (73%). Overall, 206 (68.9%) had PPF, majority 191 (92.7%) had pattern
      c, either alone (63 participants) or in combination with pattern d (128
      participants). Age of 30-50 years was significantly associated with PPF (OR 2.28
      p-value-0.003). CONCLUSION: We found high prevalence of S. mansoni and PPF in the
      HIV infected population and age was a significant factor for PPF. We recommend
      all HIV infected patients be examined routinely for S. mansoni infection for
      early anti-schistosomal treatment.

PMID- 29062325
TI  - Demographic and epidemiological characteristics of HIV opportunistic infections
      among older adults in Nigeria.
AB  - BACKGROUND: In view of the maturing HIV epidemic in sub-Saharan Africa, better
      understanding of its epidemiology among older adults is necessary in order to
      design appropriate care and treatment programmes for them. OBJECTIVES: To
      describe the demographic and epidemiological characteristics of HIV opportunistic
      infections among newly enrolled patients aged 50 years and above in Ibadan, South
      West Nigeria. METHODS: Analysis of data extracted from electronic records of 17,
      312 subjects enrolled for HIV/AIDS care and treatment between January 2006 and
      December 2014 at the ART clinic, University College Hospital, Ibadan. RESULTS:
      Age of the patients ranged from 18 to 90 years with a mean of 36.4 years (SD=
      10.3) with older adults constituting 12.0% (2075). Among older adults, about half
      (52.9%) were females. Majority (59.1%) were currently married while 25.9% were
      widowed. Prevalence of opportunistic infections was 46.6%. The commonest
      opportunistic infections (OIs) were: oral candidiasis (27.6%), chronic diarrhoea
      (23.5% and peripheral neuropathy (14.8%). Significant factors associated with
      opportunistic infections in older adults were: CD4 count less than 350 (OR=3.12,
      CI: 2.29-4.25) and hepatitis C virus co-infection (OR=2.17, CI: 1.14-4.13).
      CONCLUSION: There is need for prompt response to the peculiar challenges
      associated with the emerging shift in the epidemiology of HIV and associated
      infections in sub-Saharan Africa.

PMID- 29062326
TI  - Isolation and evaluation of Candida species and their association with CD4+ T
      cells counts in HIV patients with diarrhoea.
AB  - BACKGROUND: Gastrointestinal infection is one of the most common infections among
      HIV patients. Candida spp have been implicated in the aetiology of chronic
      diarrhoea in HIV patients, but little is known about this in Nigeria. OBJECTIVES:
      We determined the prevalence of faecal candidiasis in HIV patients in relation to
      diarrhoea, CD4 counts, and other socio-demographic factors and the spectrum of
      Candida isolates involved. METHODS: One hundred and fifty four HIV patients were
      investigated. Candida species were identified by standard techniques. Socio
      demographic and clinical information was obtained from the patients using a
      structured questionnaire. The CD4 count was estimated using a single platform
      flow cytometer. RESULTS: Candida overgrowth was detected in 61 (39.5%) HIV
      patients, and diarrhoea was associated with candidiasis in the subjects
      (P=0.001). Candidiasis was commonly detected among subjects in the 29-39 years'
      age group. A CD4 count below 200 cells/mm2 (62.3%) was a risk factor for
      acquiring candidiasis among HIV patients (P=0.001). Candida albicans (65.6%) was
      the most frequently recovered species followed by Candida krusei (16.4%) and
      Candida tropicalis (14.8%). CONCLUSION: Candidiasis is an important opportunistic
      infection in HIV-patients in Ile-Ife. There is need for regular checks for
      opportunistic infections, including candidiasis in HIV patients to monitor
      disease progression and prevent subsequent complications.

PMID- 29062327
TI  - Risk factors associated with acquiring superficial fungal infections in school
      children in South Western Nigeria: a comparative study.
AB  - INTRODUCTION: Superficial fungal infections (SFI) are caused mainly by
      dermatophytes and yeasts. SFI is of major public health concern and is a common
      cause of skin disease among school children. OBJECTIVES: The aim of this study
      was to identify the risk factors associated with acquiring superficial fungal
      infections in school children in Ile-Ife, South West Nigeria as this will assist
      in instituting appropriate interventions. METHODS: A total of 560 children; 280
      with superficial fungal infections as subjects and 280 age and sex matched school
      children as controls were recruited through multistage sampling method from 10
      primary schools (private and public owned) in Ile-Ife, Nigeria. DISCUSSION:
      Pupils were aged 5-16 years with a mean age of 9.42+/-2.00. Risk factors
      documented in this study included poor living conditions, use of barbers'
      clippers, low socio-economic status, poor hygiene, attendance of public schools
      and not living with both parents. The last four factors remained significant on
      binary logistic regression. CONCLUSION: The study shows that the risk for
      acquiring superficial fungal infections remains high in school children and in
      communities with low socio-economic positions.

PMID- 29062324
TI  - Effect of vitamin A and vitamin C supplementation on oxidative stress in HIV and
      HIV-TB co-infection at Lagos University Teaching Hospital (LUTH) Nigeria.
AB  - BACKGROUND: HIV and TB infections are both associated with elevated oxidative
      stress parameters. Anti-oxidant supplementation may offer beneficial effects in
      positively modulating oxidative stress parameters in HIV and HIV-TB infected
      patients. We investigated the effects of vitamin A and C supplementation on
      oxidative stress in HIV infected and HIV-TB co-infected subjects. METHODS: 40
      HIV/TB co-infected and 50 HIV mono-infected patients were divided into 2 equal
      groups. Participants provided demographic information and blood was collected to
      determine oxidative stress parameters before and after vitamin A (5000 IU) and C
      (2600 mg) supplementation for 1 month. RESULTS: There was a significantly (p <
      0.05) higher level of Malondialdehyde (MDA) at baseline for HIV infected subjects
      compared with HIV-TB co-infected subjects. There was a significantly (p < 0.05)
      lower level of MDA and higher level of Catalase (CAT) in subjects administered
      supplementation compared to subjects without supplementation for the HIV infected
      group. There was a significantly lower level of Reduced Glutathione (GSH),
      Superoxide Dismutase (SOD) and higher level of MDA after one month of
      supplementation compared with baseline levels for HIV/TB co infected subjects. A
      similar result was also obtained for the HIV mono-infected groups which had a
      significantly lower level of SOD, MDA and CAT compared to the baseline. There was
      a significantly lower level of GSH and SOD, and higher level of MDA after
      supplementation compared with the baseline for HIV/TB co-infected subjects.
      Comparing the indices at baseline and post no-supplementation in HIV/TB co
      infection showed no significant differences in the oxidative stress parameters.
      CONCLUSION: HIV/TB co-infection and HIV mono-infection seems to diminish the
      capacity of the anti-oxidant system to control oxidative stress, however
      exogenous anti-oxidant supplementation appears not to have beneficial roles in
      positively modulating the associated oxidative stress.

PMID- 29062328
TI  - Effect of smoking on acute phase reactants, stress hormone responses and vitamin
      C in pulmonary tuberculosis.
AB  - BACKGROUND: Chronic inflammation, possibly exacerbated by cigarette smoking, is
      considered to be the primary cause of pulmonary damage in patients with
      tuberculosis (TB). However, the mechanisms which underpin these harmful
      inflammatory responses, have not been well documented. OBJECTIVES: The current
      study was undertaken to determine possible associations between systemic
      biomarkers of inflammation (acute phase reactants, stress hormones, leukocyte
      vitamin C) and smoking status in patients (n=71, 20 smokers) with newly-diagnosed
      pulmonary TB presenting at a tertiary hospital, Johannesburg, South Africa.
      METHODS: Plasma concentrations of C-reactive protein (CRP), ferritin, cortisol,
      epinephrine, norepinephrine, dopamine and leukocyte vitamin C were measured using
      a combination of immunonephelometric, radioimmunoassay, immunochromatographic and
      spectrophotometric procedures. Demographic, clinical and laboratory data was
      captured and analysed by parametric and non-parametric analyses where
      appropriate. RESULTS: Smokers were predominantly males (P<0.0001), of older age
      (P<0.0003) with a significantly lower body mass index (P<0.03). Plasma levels of
      CRP, ferritin and dopamine were higher in the group of smokers in the setting of
      lower levels of epinephrine, and leukocyte vitamin C, with CRP and vitamin C
      attaining statistical significance (P<0.04 and P<0.02 respectively). Those of
      cortisol and norepinephrine were comparable to those of non-smokers, as were
      radiographic changes and clinical indices of disease activity. CONCLUSION:
      Cigarette smoking is associated with an exaggerated systemic inflammatory
      response in pulmonary TB in the setting of decreased concentrations of leukocyte
      vitamin C. Although no significant associations with radiographic changes and
      most clinical indices of disease activity were evident on presentation, these pro
      inflammatory interactions may have prognostic significance.

PMID- 29062329
TI  - Dissemination and genetic support of broad-spectrum beta-lactam-resistant
      Escherichia coli strain isolated from two Tunisian hospitals during 2004-2012.
AB  - BACKGROUND: The dissemination of extended-spectrum beta-lactamase (ESBL)
      producing bacteria presented a great concern worldwide. Gram-negative organisms
      such as Escherichia coli and Klebsiella pneumoniae are the most frequently
      isolated pathogens responsible for nosocomial infections. OBJECTIVES: The aim of
      this study was to investigate and to follow the emergence of resistance and the
      characterization of Extended-Spectrum Beta-Lactamases (ESBL) among broad-spectrum
      beta-lactam-Escherichia coli clinical isolates recovered from the military
      hospital and Habib Thameur hospital in Tunisia. METHODS: A total of 113 E.coli
      isolates obtained during the period 2004 through 2012 showed a significant degree
      of multi-resistance. Among these strains, the double-disk synergy test confirmed
      the ESBL phenotype in 46 isolates. These included 32(70%) strains from Hospital A
      and 14(30%) from Hospital B. RESULTS: The ESBL was identified as CTX-M-15. The
      ESBL resistance was transferred by a 60 kb plasmid CTXM-15-producing isolates
      were unrelated according to the PFGE analysis and characterization of the regions
      surrounding the blaCTX-M-15 showed the ISEcp1 elements located in the upstream
      region of the bla gene and 20 of them truncated by IS26. CONCLUSION: ESBL
      producing E. coli strains are a serious threat in the community in Tunisia and we
      should take into consideration any possible spread of such epidemiological
      resistance.

PMID- 29062330
TI  - Molecular screening of antibiotic-resistant determinants among multidrug
      resistant clinical isolates of Proteus mirabilis from SouthWest Nigeria.
AB  - BACKGROUND: Globally, and particularly in developing countries, the menace of
      anti-microbial resistance is an accelerating problem. In Nigeria, increase in
      bacterial resistance has been phenotypically established but due to high cost,
      few molecular studies have been reported. OBJECTIVES: This study screened for
      presence of transferable resistance genes and mobile genetic elements (MGEs) such
      as integron among multi-drug resistant (MDR) P. mirabilis. METHODS: A total of
      108 P. mirabilis strains collected from five tertiary hospitals in SouthWest
      Nigeria were subjected to antibiotic susceptibility study using disc-diffusion
      method. Transferable resistance genes and MGEs were amplified using Polymerase
      chain reaction (PCR) analysis and amplicons sequenced. RESULTS: Varied resistance
      was observed against all the antibiotics tested. About 56% of the isolates were
      MDR including those from 0-12 years old children. PCR analysis revealed the
      presence of aac(6')-Ib (33.3%), plasmid mediated quinolone resistance (PMQR)
      genes [qnrA (36.7%), acc(6')-Ib-cr (5%)], TEM (48.3%), CTX-M (6.7%) and integrons
      class 1 (58.3%) and class 2 (26.7%). Sequencing analysis revealed blaTEM-1,
      blaCTX-M-15 associated with ISEcp1 and eight different arrays of gene cassettes:
      aadA1, aadA1-qacH, aadB-aadA2, aadA5, dfrA7, dfrA15, dfrA17, dfrA17-aadA5.
      CONCLUSION: Transferable resistance genes in association with MGEs are present in
      Nigerian P. mirabilis thus their potential in disseminating resistance.

PMID- 29062331
TI  - Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment
      in Chronic HCV Saudi patients.
AB  - BACKGROUND: Many recent studies support the idea that osteopontin (OPN) can be
      used to predict the success of pegylated interferon (PEG IFN) alpha-2b/ribavirin
      therapy in chronic HCV patients. OBJECTIVE: Our aim was to investigate the role
      of plasma OPN and its gene polymorphism at nt - 443 in response to PEG IFN in
      Saudi patients with chronic HCV. METHODS: Blood was collected from 87 patients
      with chronic hepatitis C before treatment, then patients received PEG IFN alpha2b
      plus ribavirin combination therapy. Another 25 healthy subjects, matched for age
      and sex to patients, were enrolled as controls. Single nucleotide polymorphism
      (SNP) in OPN at nt - 443 and its blood level were analyzed. RESULTS: The
      frequency of patients who reached sustained virological response (SVR) was
      increased in patients with T/T at nt - 443 than in those with C/C or C/T. Also
      the frequency of T allele was increased in responders than in non-responders.
      However, this increase was not statistically significant. The blood level of OPN
      was significantly increased in non-responders (Mean+/-SD=37.21+/-3.9) in
      comparison to responders (Mean+/-SD=33.22+/-4.1). CONCLUSION: Osteopontin blood
      level can be considered as a reliable predictor to PEG IFN alpha2b plus ribavirin
      therapy in chronic HCV Saudi Patients.

PMID- 29062332
TI  - A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses.
AB  - BACKGROUND: Vaccine antigens targeting specific P. falciparum parasite stages are
      under pre-clinical and clinical development. It seems plausible that vaccine with
      multiple specificities will offer higher protection. With this hypothesis, we
      exploited the Spy-Tag/SpyCatcher conjugation system to make a, post expression,
      dual antigen conjugate vaccine, comprising two clinically tested antigen
      candidates (CSP and VAR2CSA). METHODS: The DBL1x-DBL2x-ID2a region of VAR2CSA was
      genetically fused with SpyTag at N-terminus. The full-length CSP antigen was
      genetically fused to C-terminal SpyCatcher peptide. The covalent interaction
      between SpyTag/SpyCatcher enables the formation of DBL1x-DBL2x-ID2a:CSP conjugate
      vaccine. Immunogenicity and quality of antibody responses induced by the
      conjugate vaccine, as well as a control CSP-SpyCatcher vaccine, was tested in
      BALB/c mice. RESULTS: Serum samples obtained from mice immunized with the
      conjugate vaccine were able to recognize both untagged DBL1x-DBL2x-ID2a as well
      as CSP antigen. Moreover, the geometric mean anti-CSP antibody titer was 1.9-fold
      higher in serum (at day 35 and 55 post-first immunization) from mice immunized
      with the conjugate vaccine, as compared to mice receiving the control vaccine.
      CONCLUSION: The data obtained in this study serves as proof-of-concept for the
      simultaneous induction of antibodies directed against individual antigen
      components in a dual stage anti-malaria vaccine.

PMID- 29062334
TI  - Does female education explain the disparity in the use of antenatal and natal
      services in Nigeria? Evidence from demographic and health survey data.
AB  - BACKGROUND: Nigeria is among the countries with a high number of annual maternal
      deaths partly due to low utilization of maternal health services (MHS).
      OBJECTIVE: This study aimed to explore whether there is an association between
      women's level of education and the appropriate use of antenatal and delivery
      services. METHOD: A quantitative cross-sectional study was used to analyze the
      Nigerian Demographic and Health Survey (NDHS) data. Information from 33,385 women
      aged 15 - 49 years was analyzed using Bivariate Pearson Chi square test and
      multiple logistic regressions. RESULTS: Education is statistically associated
      with the number of antenatal clinic visits made (AOR = 3.208; CI 2.875 - 3.578; p
      < .0001) and the place of delivery (AOR = 2.009; CI 1.449 - 2.785; p < .0001)
      even after controlling for availability of skilled health workers, parity,
      income, religion, age and distance. CONCLUSION: A long term investment in girls'
      education will improve income, interaction with health care providers, level of
      autonomy to seek and pay for appropriate MHS and ultimately use of MHS and
      positive pregnancy outcomes.

PMID- 29062335
TI  - Factors influencing women's utilization of public health care services during
      childbirth in Malawi Public health facility utilization.
AB  - BACKGROUND: Maternal mortality remains a public health challenge claiming many
      lives at the time of giving birth lives. However, there have been scanty studies
      investigating factors influencing women's use of public health facilities during
      childbirth. OBJECTIVE: The aim of the study was to explore the factors associated
      with women choice of public health facility during childbirth. METHODS: The study
      used 2010 Malawi Demographic Health Survey dataset and a binary logistics
      regression analysis to estimate the determinants influencing women's use of
      public health facilities at the time they give birth. RESULTS: Of 23020 women
      respondents, 8454(36.7%) chose to give birth in public health facilities.
      Multivariate analysis reported that frequency of antenatal care (ANC), birth
      order, women's education, wealth status and quality of care were the major
      predictors increasing women's choice to use public health facilities at
      childbirth. CONCLUSION: There is need to use multimedia approach to engage women
      on significance of utilizing public health facilities during childbirth and
      promote quality of care in facilities if their health outcome is to improve in
      Malawi.

PMID- 29062333
TI  - A qualitative study of sexual health education among Iranian engaged couples.
AB  - BACKGROUND: Sexual health education for Iranian engaged couples is always ignored
      in the premarital education program. OBJECTIVES: The aim of this study was to
      explore the necessity of sexual health education for Iranian engaged couples.
      MATERIALS AND METHODS: This qualitative study was conducted in Rasht, Iran. The
      studied sample consisted of 38 engaged men and women; and also 9 health experts
      and policymakers. We used interview guides to collect data. The data was analyzed
      through content analysis method. RESULTS: Analyzing participants' perspectives
      revealed six themes including: (1) socio-cultural changes, (2) emerging social
      pathologies, (3) inadequate sexual knowledge; (4) challenges in providing sexual
      health services, (5) individual consequences and (6) social consequences.
      CONCLUSION: Most participants emphasized the necessity of sexual health education
      not only because of medical concerns, but also from the perspective of social
      issues. Providing these services should be considered a priority.

PMID- 29062336
TI  - Uptake of long-acting reversible contraceptive devices in Western region of The
      Gambia.
AB  - BACKGROUND: The contraceptive method has become an essential factor in the life
      of most women of reproductive age group; although it varies in different stages
      of their life course. The use of long acting reversible methods (LARC) is
      proposed as a strategy to reverse undesirable maternal health consequences in
      developing countries. OBJECTIVE: To determine the uptake of long-acting
      reversible contraceptive in The Gambia. METHODS: A community based cross
      sectional study of women attending family planning clinic were studied using
      intervieweradministered questionnaire which included information on socio
      demographic factors, reproductive health and contraceptive use of the
      participants. RESULTS: About 89 % of study participants used long acting
      reversible contraceptive methods. Of the three commonly available long acting
      reversible contraceptive methods, Depo Provera was the most commonly used method;
      78 of 141 (55.32%); followed by implants (43.3%) and intrauterine contraceptive
      (1.42%). Being housewives, with 3-4 living children and having secondary level
      education were associated with high uptake of LARC. CONCLUSION: The uptake of
      long acting reversible contraceptive was high; with Depo Provera as the most
      commonly used contraceptive method in The Gambia. There seemed to be an increase
      in the uptake of implants; with intrauterine contraceptive device being the least
      commonly used method.

PMID- 29062337
TI  - Evidence for decreasing sperm count in African population from 1965 to 2015.
AB  - PURPOSE: This meta-analysis, following our previous reports those documented an
      overall 57% diminution in mean sperm concentration around the globe over past 35
      years and 32.5% decline in past 50 years in European population, attempts to
      report the declining trend of sperm concentrations in African population between
      1965 and 2015. METHODS: In the course of retrieval of data following MOOSE
      guidelines and PRISMA checklist, we found a total of fourteen studies that have
      been conducted during that period on altering sperm concentration in the African
      male. RESULTS: Following analysis of the data, a time-dependent decline of sperm
      concentration (r = -0.597, p = 0.02) and an overall 72.6% decrease in mean sperm
      concentration was noted in the past 50 years. The major matter of concern is the
      present mean concentration (20.38*106/ml) is very near to WHO cut-off value of
      2010 of 15*106/ml. Several epidemic diseases, genital tract infection, pesticides
      and heavy metal toxicity, regular consumption of tobacco and alcohol are reported
      as predominant causative factors. CONCLUSION: This comprehensive, evidence-based
      meta-analysis and systematic review concisely presents the evidence of decreased
      sperm concentration in the African male over past 50 years with possible
      causative factors to serve the scientific research zone related to male
      reproductive health.

PMID- 29062338
TI  - Allostatic load and heart rate variability as health risk indicators.
AB  - BACKGROUND: Uncertainty often exists about the comparability of results obtained
      by different health risk indicator systems. OBJECTIVES: To compare two health
      risk indicator systems, i.e, allostatic load and heart rate variability (HRV).
      Additionally, to investigate the feasibility of inclusion of HRV indicators into
      allostatic load assessments and which HRV indicators are best to introduce.
      METHODS: Allostatic loads were calculated based on blood pressure, waist-to-hip
      ratio, BMI, cholesterol, HDL-C, LDL-C, CRP, albumin, glycosylated haemoglobin,
      blood glucose and cortisol excretion. Allostatic load scores were compared to HRV
      results obtained by frequency domain, time domain and Poincare analyses. RESULTS:
      Negative correlations were found between allostatic loads and total HRV, for all
      periods and all HRV analytical techniques (r=-0.67, p=0.0001 to r=-0.435,
      p=0.035), and between allostatic loads and vagal measures of HRV for supine (r=
      0.592, p=0.001 to r=-0.584, p=0.001) and the first 5 minutes standing (r=-0.443,
      p=0.021 to r=-0.407, p=0.035), with all HRV techniques. Heart rate responses
      declined with increases in allostatic loads. CONCLUSION: HRV and allostatic load
      scores give comparable results as health risk indicators. Baseline total HRV and
      vagal, rather than sympathetic, measures of HRV should be introduced into
      allostatic load assessments. Results are in line with the concept of vagal tone
      as a regulator of allostatic systems. Inclusion of heart rate responses to
      orthostatic stress, into allostatic load assessments, warrants further
      investigation.

PMID- 29062339
TI  - An under-diagnosed geriatric syndrome: sleep disorders among older adults.
AB  - INTRODUCTION: Sleep disorders are commonly under-diagnosed in the geriatric
      population. We aimed to determine the prevalence of sleep problems among older
      adults admitted to the geriatrics out-patient clinic. METHODS: Two hundred and
      three patients (136 female) older than 75 years of age were included in the
      study. Patients underwent comprehensive geriatric assessment, including
      identification of sleep problems using the Sleep Disturbance Scale, Rapid eye
      movement (REM) sleep behavior disorder (RBD) Single-Question Screen questionnaire
      (RBD1Q) and The Johns Hopkins Restless Leg Syndrome Severity Scale. Demographic
      and clinical data including age, sex, medications, comorbid diseases, body mass
      index and functional scores was noted. RESULTS: The mean age of the patients was
      80.92+/-4.3 years. 35.5% of the patients had findings of REM-SBD and 32.5% of the
      patients had restless legs syndrome. Ninety-seven percent of the patients
      answered 'yes' to at least one of the sleep disturbance scale questions. There
      was no significant difference between male and female groups. CONCLUSION: We
      observed that sleep disorders were common among older adults. For this reason,
      the course and quality of sleep should be examined in all patients as a routine
      part of comprehensive geriatric assessment.

PMID- 29062340
TI  - Biochemical markers of mineral bone disorder in South African patients on
      maintenance haemodialysis.
AB  - BACKGROUND AND OBJECTIVE: Despite the high mortality and morbidity associated
      with abnormalities in mineral and bone metabolism in haemodialysis patients,
      there is limited data on the pattern of mineral bone disorder in African CKD
      population. Therefore, the purpose of this study was to describe the pattern of
      mineral bone disease by evaluating biochemical parameters in patients on
      maintenance haemodialysis (MHD). METHODS: We evaluated the serum/plasma intact
      parathyroid hormone (iPTH), corrected calcium, phosphate, total alkaline
      phosphatase (TALP) and 25 -OH vitamin D levels of two hundred and seven patients
      undergoing MHD at two dialysis centers in Johannesburg. RESULTS: The MHD patients
      (133 men, 74 women) had a mean age of 54.5+/-15.6 years with a median dialysis
      vintage of 24 months (IQR, 12-48) and a mean kt/V of 1.45+/-0.28. The prevalence
      of hyperparathyroidism (iPTH >150 pg/ml), hyperphosphataemia, hypocalcaemia and
      25-OH vitamin D deficiency (<30 ng/ml) was 73.4%, 57.0%, 20.3% and 80.7 %
      respectively. The combination of markers of bone turnover (iPTH >150pg/ml and
      TALP> 112 U/L) suggestive of high turnover bone disease, was present in 47.3 % of
      the study population. In multiple-logistic regression analysis, the odds ratio
      for developing hyperparathyroidism with hypocalcaemia and hyperphosphataemia were
      5.32 (95% CI 1.10 - 25.9, P = 0.03) and 3.06(95 % CI 1.15 - 8.10, P=0.02)
      respectively. Ninety eight (47.3%) of the MHD patients had iPTH within the
      recommended kidney disease improving global outcome (KDIGO) guidelines.
      CONCLUSION: Secondary hyperparathyroidism and 25-OH vitamin D deficiency were
      common in our haemodialysis patients. Hypocalcaemia and hyperphosphataemia were
      strong predictors for developing secondary hyperparathyroidism.

PMID- 29062342
TI  - Prevalence, severity and factors associated with peripheral neuropathy among
      newly diagnosed diabetic patients attending Mulago hospital: a cross-sectional
      study.
AB  - AIMS: To determine the prevalence and associated risk factors of diabetic
      peripheral neuropathy (DPN) among newly diagnosed diabetes mellitus patients in
      Mulago Hospital. METHODS: A cross-sectional study was conducted among 248 newly
      diagnosed adult diabetic patients. Using the standard Neuropathy Symptom Score
      (NSS) and Neuropathy Disability Score (NDS) criteria, we screened them for
      neuropathy. Data on the socio-demographics, age, duration of symptoms and history
      of diabetic ulcer were analyzed using a multiple logistic regression. A p-value
      <0.05 was considered significant. RESULTS: The majority of study patients (62.1%)
      were male. The overall prevalence of DPN was 29.4 %. Nearly sixteen percent had
      moderate neuropathy and only five percent had severe neuropathy. Age above 60
      years was significantly associated with the presence of DPN; (OR 3.72; 95% CI
      1.25 - 11.03; p=0.018). The history of ever having a foot ulcer was significantly
      associated with peripheral neuropathy (OR 2.59; 95% CI: 1.03 - 6.49, p = 0.042).
      CONCLUSION: DPN occurs in 1 in 4 of newly diagnosed diabetic patients in Mulago
      hospital. Two thirds of these patients had moderate to severe neuropathy. DPN was
      independently associated with increasing age. Early diagnosis of diabetes
      mellitus, increased diabetes knowledge and regular blood sugar screenings would
      play an important role in identifying this problem.

PMID- 29062345
TI  - Distraction-related road traffic collisions.
AB  - OBJECTIVES: We aimed to prospectively study distraction-related road traffic
      collision injuries, their contributory factors, severity, and outcome. METHODS:
      Data were prospectively collected on all hospitalized road traffic collision
      trauma patients in Al-Ain City who were drivers at the collision time over one
      and half years. Driver's inattentive behaviors preceding the collision were
      collected by interviewing the admitted drivers. RESULTS: There were 444 drivers,
      330 of them were fully oriented patients, out of them only 44 (13%) were
      distracted. Nineteen (5.8%) drivers were distracted by using mobile phones, 12
      (3.6%) were pre-occupied with deep thinking, six (1.8%) were talking with other
      passengers, four (1.2%) were picking things in the vehicle, and three (0.9%) were
      using entertainment systems. The maximum distraction occurred during the time of
      6 am - 12 noon when the traffic was crowded. There were no significant
      differences between distracted and non-distracted drivers in demographical and
      physiological factors, injured regions, and outcomes. CONCLUSION: Distraction of
      alert drivers causes 13% of road traffic collisions in Al-Ain city. About 40
      percent of the distracted drivers involved in road traffic collisions (RTC) were
      using mobile phones. Our study supports the ban of use of cell phones while
      driving.

PMID- 29062341
TI  - Changes in mediators of inflammation and pro-thrombosis after 12 months of
      dietary modification in adults with metabolic syndrome.
AB  - OBJECTIVE: This study evaluated the effects of a 12-month dietary modification on
      indices of inflammation and pro-thrombosis in adults with metabolic syndrome
      (MS). MATERIALS AND METHODS: This longitudinal study involved 252 adults with MS
      recruited from the Bodija market, Ibadan and its environs. Participants were
      placed on 20%, 30% and 50% calories obtained from protein, total fat and
      carbohydrate respectively and were followed up monthly for 12 months.
      Anthropometry and blood pressure were measured using standard methods. Fasting
      plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high density
      lipoprotein-cholesterol (HDL-C), fibrinogen, plasminogen activator inhibitor-1
      (PAI-1)], interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured using
      spectrophotometric methods and ELISA as appropriate. Data was analysed using
      ANCOVA, Student's t-test, Mann-Whitney U and Wilcoxon signed-rank tests. P-values
      less than 0.05 were considered significant. RESULTS: After 6 months of dietary
      modification, there was a significant reduction in waist circumference (WC),
      while the levels of HDL-C, fibrinogen and PAI-1 were significantly increased when
      compared with the corresponding baseline values. However, WC and fibrinogen
      reduced significantly, while HDL-C and IL-10 significantly increased after 12
      months of dietary modification as compared with the respective baseline values.
      CONCLUSION: Long-term regular dietary modification may be beneficial in
      ameliorating inflammation and pro-thrombosis in metabolic syndrome.

PMID- 29062343
TI  - Expression of miR-126 and its potential function in coronary artery disease.
AB  - OBJECTIVE: This study aimed to explore the role of miR-126 in coronary artery
      disease (CAD) patients and the potential gene targets of miR-126 in
      atherosclerosis. METHODOLOGY: A total of 60 CAD patients and 25 healthy control
      subjects were recruited in this study. Among the 60 CAD patients, 18 cases were
      diagnosed of stable angina pectoris (SAP), 20 were diagnosed of unstable angina
      pectoris (UAP) and 22 were diagnosed of acute myocardial infarction (AMI). Plasma
      miR-126 levels from both groups of participants were analyzed by real-time
      quantitative PCR. ELISA was used to measure plasma level of placenta growth
      factor (PLGF). RESULTS: The results showed that the miR-126 expression was
      significantly down-regulated in the circulation of CAD patients compared with
      control subjects (P<0.01). Plasma PLGF level was significantly upregulated in
      patients with unstable angina pectoris and acute myocardial infarction (AMI)
      compared with controls (both P<0.01) the miR-126 expression in AMI was
      significantly associated with PLGF. CONCLUSION: miR-126 may serve as a novel
      biomarker for CAD.

PMID- 29062344
TI  - Assessment of hospital-based adult triage at emergency receiving areas in
      hospitals in Northern Uganda.
AB  - BACKGROUND: Limited health service resources must be used in a manner which does
      "the most for the most". This is partly achieved through the use of a triage
      system. Whereas efforts have been made to introduce paediatric triage in Uganda
      such as Emergency Triage Assessment and Treatment Plus (ETAT+), it is not clear
      if hospitals have local protocols for adult triage being used in each setting.
      OBJECTIVES: To determine the presence of existing hospital triage systems, the
      cadre of staff undertaking triage and barriers to development/improvement of
      formal triage systems. METHODOLOGY: This was a descriptive cross-sectional study.
      Acholi sub-region was randomly selected for the study among the three sub-regions
      in Northern Uganda. The study was conducted in 6 of the 7 hospitals in the
      region. It was a written self-administered questionnaire. RESULTS: Thirty-three
      participants from 6 hospitals consented and participated in the study. Only one
      hospital (16.7%) of the 6 hospitals surveyed had a formal hospital-based adult
      triage protocol in place. Only 2 (33.3%) hospitals had an allocated emergency
      department, the rest receive emergency patients/perform triage from OPD and
      wards. Lack of training, variation of triage protocols from hospital to another,
      shortage of staff on duty, absence of national guidelines on triage and poor
      administrative support were the major barriers to improvement/development of
      formal triage in all these hospitals. CONCLUSION: Formal adult hospital-based
      triage is widely lacking in Northern Uganda and staff do perform subjective
      "eyeball" judgments to make triage decisions.

PMID- 29062346
TI  - Effect of low-dose ketamine on post-operative serum IL-6 production among
      elective surgical patients: a randomized clinical trial.
AB  - BACKGROUND: Surgery and Anesthesia cause an excessive pro-inflammatory response.
      Mulago Hospital is faced with staff shortage making post-operative pain
      management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial
      cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We
      hypothesized that its attenuation of serum IL-6 was a surrogate for clinical
      benefit. MATERIALS AND METHODS: Institutional Review Board's approval was sought
      and RCT was registered at clinical trials.gov (identifier number: NCT01339065).
      Consenting patients were randomized to receive pre-incision intravenous ketamine 
      0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected
      and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours
      respectively. RESULTS: We recruited 39 patients of whom 18 were randomized to the
      ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum
      IL-6 and IL-1beta levels were analyzed using ELIZA assay of pre-coated micro
      wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours.
      There was no reaction in 98% of IL-1beta assayed. CONCLUSION: Low-dose ketamine
      attenuated early serum IL-6 levels due to surgical response with reduced 24 hour
      increase, but the difference was not statistically significant and we recommend
      more studies.

PMID- 29062347
TI  - Major limb amputations in a tertiary hospital in North Western Nigeria.
AB  - BACKGROUND: Amputation is the removal of whole or part of a limb, often as a life
      saving measure. It is a mutilating surgical procedure altering the body image and
      producing severe functional deficit. It is a common orthopedic surgical procedure
      performed worldwide. AIMS AND OBJECTIVES: The aim of this study was to determine
      the pattern and indications for amputation in Federal Medical Centre, Birnin
      Kebbi, Kebbi State, Nigeria; between January 2008 and December 2014, in a bid to
      proffer preventive measures. PATIENTS AND METHODS: This was a retrospective study
      of consecutive patients who had major limb amputations at the Federal Medical
      Centre, Birnin Kebbi, Kebbi State, Nigeria; between January 2008 and December
      2014. Case notes of patients were retrieved with relevant information extracted
      and analyzed. RESULTS: A total of 112 amputations were studied. The age range of
      patients was between 3-89 years. Amputation in 23.5% of patients was due to
      trauma, followed by diabetic foot gangrene in 21% of cases. About 42.9% of the
      amputations were above knee, followed by below knee amputations in 37% of cases.
      The lower limbs were involved in 84.8% of cases and upper limbs in 15.2% of
      cases. CONCLUSION: Trauma was the most predominant indication for amputation in
      this study. This was followed by diabetic foot gangrene. This is usually due to
      the high rate of road traffic accidents and consequent mismanagement by
      traditional bone setters.

PMID- 29062349
TI  - Lifestyle factors influencing bone health in young adult women in Saudi Arabia.
AB  - AIM: To analyze risk factors leading to osteopenia and osteoporosis among young
      female students. METHODS: Quantitative Ultrasonography measurements were
      performed in the calcaneal region of 101 young Saudi females. Dietary habits,
      exercising and sun exposure were assessed using questionnaires. The association
      between the different studied factors was assessed by Pearson test and multiple
      linear regression model. RESULTS: Participants diagnosed with either osteopenia
      or osteoporosis (>33%.) showed significant higher soft drinks consumption,
      reduced exercise, limited intake of milk and dairy products, calcium and vitamin
      D supplementation compared to the healthy group. Multiple regression analysis
      showed that T-score and Z-score were negatively associated with soft drink intake
      and positively associated with exercising, milk and dairy products consumption,
      and calcium and vitamin D supplementation use (p <0.05). CONCLUSION: High soft
      drink intake, lack of exercising and limited calcium and vitamin D
      supplementation are the combined lifestyle factors leading to osteopenia and
      osteoporosis among young Saudi females. These findings might serve as a basis of
      nutrition education intervention to promote healthy bones among this population.

PMID- 29062348
TI  - Disordered eating attitudes: demographic and clinico-anthropometric correlates
      among a sample of Nigerian students.
AB  - OBJECTIVES: We set out in this study to determine the demographic and clinico
      anthropometric correlates of disordered eating attitudes among undergraduate
      students of two higher institutions in Lagos, Nigeria. METHODS: This cross
      sectional descriptive study was conducted among 1,054 participants after written
      informed consent. A socio-demographic questionnaire, the Eating Attitude Test
      (EAT-26) and 12-item General Health Questionnaire (GHQ-12) were administered to
      the participants. In addition, their blood pressure, height and weight were
      measured, and body mass index (BMI) was calculated. RESULTS: The study
      participants comprised of 561(55.6%) males with median age of 21.4 years. The
      mean (+/-SD) score on EAT-26 was 11.52(+/-8.54), and 16% of all the respondents
      were categorized as having disordered eating attitude. A significant relationship
      was found between disordered eating attitude and age (p= 0.027), gender (p=
      <0.001), institution of study (p= 0.005), systolic blood pressure (p=0.019), BMI
      (p= 0.027) and psychological distress (p=0.005). CONCLUSION: Our study observed
      disordered eating attitude to be prevalent among young adults, and demographic
      along with clinico-anthropometric factors constituted associated factors. Our
      findings strengthen the basis to incorporate health awareness programs aimed at
      improving nutrition and eating behavior among the young adult population. Future
      research is needed.

PMID- 29062350
TI  - Secular trend of the leading causes of death in China from 2003 to 2013.
AB  - BACKGROUND: To analyze the epidemiological characteristics and secular trends of
      the leading causes of death in China. METHODS: Data on the leading causes of
      death was collected from the Statistical Yearbook of China. Data for 11 years,
      from 2003 to 2013, was analyzed by regression analysis and chi-square test.
      RESULTS: The top 3 causes of death from 2009 to 2013 were cancer, cerebrovascular
      disease, and cardiopathy, with the role of cardiopathy increasing over time
      (P<0.01). The proportion of deaths related to cardio-cerebrovascular diseases in
      urban and rural areas increased to 41.9% and 44.8%, respectively, in 2013, and
      was significantly higher than that for cancer, 25.5% and 22.4% (both P<0.01).
      Injury and poisoning in urban or rural areas represented the fifth leading cause
      of death. In 2006, endocrine, nutritional, and metabolic diseases were the sixth
      main cause of death, with 3.3% in urban areas. The role of genito-urinary,
      respiratory, and digestive system diseases in urban areas and genito-urinary
      system diseases in rural areas decreased during this period (all P<0.05).
      CONCLUSION: Cancer, cerebrovascular disease, and cardiopathy accounted for more
      than 67% of all deaths from 2007 to 2013 in China, and significantly increased in
      proportion from 2003 to 2013.

PMID- 29062351
TI  - Family type, domestic violence and under-five mortality in Nigeria.
AB  - BACKGROUND: Nigeria still showcases unacceptably high under-five mortality
      despite all efforts to reduce the menace. Investigating the significant
      predictors of this occurrence is paramount. OBJECTIVE: To examine the interplay
      between family setting, domestic violence and under-five death in Nigeria.
      METHODS: Cross-sectional secondary data, the 2013 Nigeria Demographic and Health
      Survey, (NDHS) women dataset was utilized. Subset of 26,997 ever married and ever
      had childbirth experience respondents were extracted from the nationally
      representative women dataset. Dependent and Independent variables were recoded to
      suit the statistical analysis for the study. RESULTS: The study revealed that
      33.7% of the respondents were in polygyny family setting; one-quarter of the ever
      married women reported ever experiencing one form of domestic violence or the
      other. The results of the logistic regressions indicate that family type and
      domestic violence were significant predictors of under-five children mortality in
      Nigeria. CONCLUSION: The study concludes that women who belong to polygyny family
      setting and who ever experienced sexual domestic violence are highly susceptible
      to experience under-five children mortality than their counterparts. The study
      recommends that strategies and policies aimed at improving child survival should
      strengthen women empowerment initiatives, discourage multiple wives and campaign
      against domestic violence in Nigeria.

PMID- 29062352
TI  - Near vision spectacle coverage and barriers to near vision correction among
      adults in the Cape Coast Metropolis of Ghana.
AB  - PURPOSE: To determine the near vision spectacle coverage and barriers to
      obtaining near vision correction among adults aged 35 years and older in the Cape
      Coast Metropolis of Ghana. METHODS: A population-based cross-sectional study
      design was adopted and 500 out of 576 participants aged 35 years and older were
      examined from 12 randomly selected clusters in Cape Coast, Ghana. All
      participants underwent a comprehensive eye examination which included: distance
      and near visual acuities measurements and external and internal ocular health
      assessments. Distance and near refractions were performed using subjective
      refraction technique. Information on participants' demographics, near vision
      correction status, near visual needs and barriers to acquiring near vision
      correction were obtained through a questionnaire administered as part of the
      study. RESULTS: The mean age of participants was 52.3+/-10.3 years of whom 280
      (56%) were females and 220 (44%) were males. The near vision spectacle coverage
      was 25%, 33% "met need" for near vision correction in the presbyopic population,
      and 64% unmet need in the entire study population. After controlling for other
      variables, age (5th and 6th decades) and educational level were associated with
      "met need" for near vision correction (OR=2.7 (1.55-4.68), p =0.00, and OR=2.36
      (1.18-4.72), p=0.02 respectively). Among those who needed but did not have near
      vision correction, 64 (26%) did not feel the need for correction, 55 (22%) stated
      that they were unaware of available interventions, and 53 (21%) found the cost of
      near vision correction prohibitive. CONCLUSION: There was a low near vision
      spectacle coverage in this population which suggests the need for strategies on
      health education and promotion to address the lack of awareness of spectacle need
      and cost of services.

PMID- 29062353
TI  - Why should modified Atkins diet be encouraged for treating epilepsy in emerging
      countries?

PMID- 29062354
TI  - Vitamin B6 and homocysteine levels in carbamazepine treated epilepsy of Khyber
      Pakhtunkhwa.
AB  - OBJECTIVES: The study focused on the plasma levels of vitamin B6 and homocysteine
      in different genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes
      in carbamazepine resistant epilepsy in the population of Khyber Pakhtunkhwa.
      METHODOLOGY: Patients who were possible candidates for carbamazepine therapy were
      followed for six months for their seizure control. Plasma levels of vitamin B6
      and homocysteine were determined using immunoassay based techniques at baseline
      and after six months. MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes were
      genotyped using restriction fragment length polymorphisms. Seizure control during
      therapy was recorded on a standardized proforma. RESULTS: Low vitamin B6 levels
      and hyperhomocysteinemia were found in 61.7% of resistant patients (n=34).
      Resistant patients had the following frequencies of variant genotypes
      (677CT=38.1% and 677TT=24.4%; 1298AC=42.2% and 1298CC=26.1%; 588CT= 47.6% and
      315TT= 33.3%) of MTHFR (C677T and A1298C) and GABRG2 (C588T and C315T) genes. A
      significant decline in vitamin B6 (P<0.0001) and hyperhomocysteinemia were found
      in variant genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes.
      CONCLUSION: Following six months of carbamazepine of therapy in heterozygous
      variant genotypes of MTHFR (677CT and 1298AC) and GABRG2 (588CT and 315CT) genes,
      we observed a significant fall in vitamin B6 levels and hyperhomocysteinemia.

PMID- 29062355
TI  - Characterization and antitumor activity of camptothecin from endophytic fungus
      Fusarium solani isolated from Camptotheca acuminate.
AB  - BACKGROUND: Camptothecin (CPT) is a potent drug against cancers, originally from
      plants. The endophytic fungi could produce the secondary metabolite same as the
      host and is used as medicine. OBJECTIVES: The aim of this paper was to
      investigate an endophytic fungal CPT with anti-neoplastic activity. METHODS:
      Endophytic fungi were isolated from Camptotheca acuminata in China. CPT from
      strain S-019 was characterized by TLC, HPLC and EI-MS analysis. Anti-tumor
      activity of fungal CPT was detected by MTT and fluorescent dye methods using Vero
      and PC-3 cells. RESULTS: A total of 94 endophytic fungi strains were isolated
      from tissues of C. acuminata and 16 fungi strains displayed cytotoxic activity on
      Vero or PC3 cells. Of which, the fungal strain S-019, classified as Fusarium
      solani, displayed impressive cytotoxic activity on cancer cells and was found to
      produce CPT by analysis of TLC, HPLC and EI-MS methods. Bioassay studies
      confirmed that the fungi CPT had potent cytotoxicity on Vero cells and induced
      apoptosis of Vero cells. CONCLUSION: The endophytic fungi from camptotheca trees
      are a reliable source for natural anticancer compounds. The endophytic fungi
      could produce CPT same as plant. The fungal CPT exhibited effective activity at
      inhibiting cell growth and inducing apoptosis on Vero cells.

PMID- 29062356
TI  - Psychosocial health challenges of the elderly in Nigeria: a narrative review.
AB  - BACKGROUND: Globally, national health systems are challenged to build successful
      aging models to prepare for biomedical, psychological and social changes. The
      integral component of psychosocial health in overall quality of life and well
      being, however, is underscored and requires greater focus. Changing demographics
      in Nigeria, in addition to cultural considerations and absence of a social
      security system, present unique challenges to elderly. OBJECTIVE: We aimed to
      review the literature that describes the current situation and challenges in
      psychosocial health status in the elderly in Nigeria and provide recommendations
      that promote health and well-being during the aging process. RESULTS: Four
      primary factors affect psychosocial health status of elderly Nigerians, namely:
      changes in family dynamics, increased demand for healthcare services, increased
      economic stress, and decreased functional independence. CONCLUSION: Like other
      developing countries, the Nigerian national system faces similar challenges in
      preparing a national framework that can maximize coverage to citizens in the
      midst of demographic changes in aging. By focusing on five target areas such as
      the educational system, health services, community-based initiatives, local or
      regional policies and national strategies, current framework in Nigeria can be
      modified to prepare for changing demographics in aging.

PMID- 29062357
TI  - Responsible conduct of research: enhancing local opportunities.
AB  - INTRODUCTION: Research integrity is the foundation of credible research and a pre
      requisite for a successful academic research environment. Lately, a lot of
      revelations of fraud and other unacceptable behaviour in research have been
      highly publicized in scientific journals and mass media. Whereas institutions in
      developed countries have developed guidelines and regulations to ensure
      responsible conduct of research and appropriately deal with cases of research
      misconduct, low- and middle-income countries seem to be lagging behind. In
      Uganda, there seems to be lack of coordinated efforts to address the problem of
      research misconduct both at the national and institutional level. OBJECTIVE: To
      propose a framework for fostering scientific integrity and deterring misconduct
      in research in Ugandan research and academic institutions. METHODS: A review of
      literature on scientific integrity, scientific misconduct, responsible conduct of
      research, and international ethical guidelines was done. RESULTS: Basing on the
      2012 Inter-Academy Council policy report, initiatives to promote responsible
      conduct of research in Ugandan research and academic institutions are proposed.
      CONCLUSION: With the proposed framework, an honest and trustworthy research
      enterprise in Uganda based on principles of scientific integrity is envisioned.

PMID- 29062358
TI  - Effect of economic and security challenges on the Nigerian health sector.

PMID- 29062360
TI  - Humidity is an ambient parameter to development of Zika virus: an Indonesian
      case.

PMID- 29062359
TI  - Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case
      report.
AB  - BACKGROUND: Dysphagia is common in inflammatory myopathies and usually responds
      to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic
      gastrostomy is associated with significant morbidity and high mortality. CLINICAL
      CASE: A 56-year old African Black woman initially presented with systemic
      sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded
      to high dose corticosteroids and cyclophosphamide followed by azathioprine, with
      improvement in her lung function and regression of the skin changes. Six years
      later she had a myositis flare with severe dysphagia. Her myositis improved after
      high doses of corticosteroids, azathioprine and two doses of intravenous
      immunoglobulin (IVIG). As her dysphagia persisted, she was fed via a percutaneous
      endoscopic gastrostomy (PEG) tube and given a course of rituximab. Her dysphagia
      gradually resolved and the PEG tube was removed within two months. She received
      another dose of rituximab six months later and continued low dose prednisone and
      azathioprine. Her muscle power improved, weight returned to normal and she
      remained well 20 months after hospital discharge. CONCLUSION: Our patient with
      SSC-myositis overlap and severe dysphagia requiring PEG feeding, improved with
      high dose corticosteroids, azathioprine, two courses of IVIG and rituximab, and
      remained in remission 20 months after hospital discharge.

PMID- 29062361
TI  - Emerging epidemic of drug resistant tuberculosis in vulnerable populations of
      developing countries.

PMID- 29062362
TI  - Assessment of Elementary School Teachers' Level of Knowledge and Attitude
      regarding Traumatic Dental Injuries in the United Arab Emirates.
AB  - INTRODUCTION: In this cross-sectional study, the level of knowledge and attitude
      of elementary school teachers regarding traumatic dental injuries (TDI) were
      assessed. MATERIALS AND METHODS: A questionnaire was distributed to 330
      elementary school teachers in 30 randomly selected schools in the Emirates of
      Sharjah and Dubai. The questionnaire collected information on participants'
      demographic characteristics, first aid training, and attitude about emergency
      management of TDI. RESULTS: 292 teachers (88%) completed the questionnaires; of
      these, 95% were females, and 50% of the participants had first aid training.
      Knowledge about tooth avulsion was inadequate, and first aid training was not
      associated with correct responses to management of avulsed teeth (p > 0.05). A
      significantly higher percentage of younger teachers (p < 0.05) expressed the need
      for future education on TDI management. A significantly higher percentage of
      participants who had an educational position (95%) indicated that they did not
      have enough knowledge regarding TDI compared to physical education teachers (79%)
      and administrators (87%) (p < 0.05). CONCLUSIONS: Elementary school teachers in
      the UAE have a low level of knowledge regarding the management of dental trauma.
      Educational programs that address TDI are needed and could improve the elementary
      school teachers' level of knowledge in emergency management of TDI.

PMID- 29062363
TI  - Diffuse Idiopathic Skeletal Hyperostosis: Persistent Sore Throat and Dysphagia in
      an Elderly Smoker Male.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) is rarely symptomatic. However,
      it can present with dyspnea, hoarseness, dysphagia, and stridor. An 80-year-old
      chronic smoker male presented with 6-month history of sore throat and progressive
      dysphagia. Computed tomography of the neck revealed bulky anterior bridging
      syndesmophytes along the anterior aspect of the cervical spine and facet effusion
      involving four contiguous vertebrae consistent with DISH. Dysphagia secondary to
      DISH was diagnosed. Fiberoptic laryngoscopy showed bilateral vocal cord
      paralysis. Patient's airway became compromised requiring tracheostomy tube
      placement. After discussion of therapeutic options, patient agreed on a
      percutaneous endoscopic gastrostomy tube insertion for nutritional support.
      Osteophytectomy was left to be discussed further.

PMID- 29062364
TI  - Alcohol Inhibits Odontogenic Differentiation of Human Dental Pulp Cells by
      Activating mTOR Signaling.
AB  - Long-term heavy alcohol consumption could result in a range of health, social,
      and behavioral problems. People who abuse alcohol are at high risks of seriously
      having osteopenia, periodontal disease, and compromised oral health. However, the
      role of ethanol (EtOH) in the biological functions of human dental pulp cells
      (DPCs) is unknown. Whether EtOH affects the odontoblastic differentiation of DPCs
      through the mechanistic target of rapamycin (mTOR) remains unexplored. The
      objective of this study was to investigate the effects of EtOH on DPC
      differentiation and mineralization. DPCs were isolated and purified from human
      dental pulps. The proliferation and odontoblastic differentiation of DPCs treated
      with EtOH were subsequently investigated. Different doses of EtOH were shown to
      be cytocompatible with DPCs. EtOH significantly activated the mTOR pathway in a
      dose-dependent manner. In addition, EtOH downregulated the alkaline phosphatase
      activity, attenuated the mineralized nodule formation, and suppressed the
      expression of odontoblastic markers including ALP, DSPP, DMP-1, Runx2, and OCN.
      Moreover, the pretreatment with rapamycin, a specific mTOR inhibitor, markedly
      reversed the EtOH-induced odontoblastic differentiation and cell mineralization.
      Our findings show for the first time that EtOH can suppress DPC differentiation
      and mineralization in a mTOR-dependent manner, indicating that EtOH may be
      involved in negatively regulating the dental pulp repair.

PMID- 29062365
TI  - Comparing the Profile of Temperament and Character Dimensions in Patients with
      Major Depressive Disorder and Bipolar Mood Disorder with a Control Group.
AB  - Objective: This study was conducted to compare the profile of temperament and
      character dimensions in patients with major depressive disorder and bipolar mood
      disorder with a control group. Method: In this causal-comparative study, the
      population consisted of 2 clinical groups (major depressive disorder and bipolar
      mood disorder) and a non-clinical group. The sample was 193 individuals (77
      patients with major depressive disorder, 86 patients with bipolar mood disorder,
      and 30 controls), with an age range of 18 to 65 years and the mean age of 40.1.
      They were selected from Roozbeh psychiatric hospital using available sampling
      method. Tools used in this research included Temperament and Character Inventory
      140 and General Health Questionnaire-28. Collected data were analyzed by
      independent t test and one-way analysis of variance using Statistical Package for
      the Social Sciences-22 software. Results: The results revealed a significant
      difference among groups in dimensions of novelty seeking, harm avoidance,
      persistence, self-directedness, and cooperativeness (P <0.05). The results showed
      that the mean was different in males and females only in the novelty seeking
      dimension (P <0.05). Conclusion: In general, our results revealed that patients
      with major depressive disorder and bipolar mood disorder have different
      personality profiles in some dimensions of temperament and character compared
      with the control group.

PMID- 29062366
TI  - Comparison of Saffron and Fluvoxamine in the Treatment of Mild to Moderate
      Obsessive-Compulsive Disorder: A Double Blind Randomized Clinical Trial.
AB  - Objective: There are different pathophysiological mechanisms for obsessive-
      compulsive disorder (OCD) as suggested by the serotonergic, dopaminergic, and
      glutamatergic hypotheses. The present study aimed at comparing the efficacy and
      safety of saffron (stigma of Crocus sativus) and fluvoxamine in the treatment of
      mild to moderate obsessive- compulsive disorder. Method: In this study, 50 males
      and females, aged 18 to 60 years, with mild to moderate OCD, participated. The
      patients were randomly assigned to receive either saffron (30 mg/day, 15 mg twice
      a day) or fluvoxamine (100 mg/day) for 10 weeks. Using the Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) and the Adverse Event Checklist, we assessed the
      patients at baseline, and at the second, fourth, sixth, eighth, and tenth week.
      Finally, the data were analyzed using general linear repeated measures. Results:
      In this study, 46 patients completed the trial. General linear repeated measures
      demonstrated no significant effect for time-treatment interaction on the Y-BOCS
      total scores [F (2.42, 106.87) = 0.70, P = 0.52], obsession Y-BOCS subscale
      scores [F (2.47, 108.87) = 0.77, p = 0.49], and compulsion Y-BOCS subscale scores
      [F (2.18, 96.06) = 0.25, P = 0.79]. Frequency of adverse events was not
      significantly different between the 2 groups. Conclusion: Our findings suggest
      that saffron is as effective as fluvoxamine in the treatment of patients with
      mild to moderate OCD.

PMID- 29062367
TI  - Stigma Barriers of Mental Health in Iran: A Qualitative Study by Stakeholders of
      Mental Health.
AB  - Objective: Many people who access mental health services usually do not seek
      treatment to avoid the consequences of stigma and label of mental illness. Thus,
      determining each aspect related to stigma reduction barriers seems necessary.
      This qualitative study was conducted to investigate stigma reduction barriers
      towards mental disorders in Iran. Method: In this study that was conducted from
      2013 to 2015, content analysis was used and all stakeholders were selected by
      purposive sampling technique. All data were obtained through 16 individual
      interviews, 2 focus groups, and 6 written narratives. The data were collected,
      coded, and analyzed accordingly. Results: The major themes were as follow: The
      universality of stigma, beliefs, attitudes and lack of awareness, mental health
      providers and other specialists, cultural barriers, structures and policymakers,
      and insufficient financial resources. Conclusion: It is necessarily to identify
      the barriers of stigma reduction programs in Iran to increase the quality of life
      of patients with mental disorders. In the present study, due to the presence of
      mental health stakeholders, the main barriers were obtained.

PMID- 29062368
TI  - Psychometric Properties of the Persian Version of Death Depression Scale-Revised
      in Iranian Patients with Acute Myocardial Infarction.
AB  - Objective: Limited research has examined the psychometric properties of death
      depression scales in Persian populations with cardiac disease despite the need
      for valid assessment tools for evaluating depressive symptoms in patients with
      life-limiting chronic conditions. The present study aimed at evaluating the
      reliability and validity of the Persian Version of Death Depression Scale -
      Revised (DDS-R) in Iranian patients who had recent acute myocardial infarction
      (AMI). Method: This psychometric study was conducted with a convenience sample of
      407 patients with AMI diagnosis who completed the Persian version of the DDS-R.
      The face, content, and construct validity of the scale were ascertained. Internal
      consistency, test-retest, and construct reliability (CR) were used to assess
      reliability of the Persian Version of DDS-R. Results: Based on maximum likelihood
      exploratory factor analysis and consideration of conceptual meaning, a 4-factor
      solution was identified, explaining 75.89% of the total variance. Goodness-of-fit
      indices (GFI), Comparative Fit Index (CFI), Normed Fit Index (NFI), Incremental
      Fit Index (IFI), and Root Mean Square Error of Approximation (RMSEA) in the final
      DDS-R structure demonstrated the adequacy of the 4-domain structure. The internal
      consistency, construct reliability, and Intra-class Correlation Coefficients
      (ICC) were greater than .70. Conclusion: The DDS-R was found to be a valid and
      reliable assessment tool for evaluating death depression symptoms in Iranian
      patients with AMI.

PMID- 29062369
TI  - Evaluation of Bipolar Disorder in Several Relapses over Time Using Generalized
      Estimating Equations.
AB  - Objective: Bipolar disorder is defined as a common and severe chronic disorder
      that causes several problems in a person's psychosocial functioning. This study
      aimed at modeling the development of bipolar disorder episodes using its
      determinant risk factors over time. Method: This retrospective cohort study was
      conducted in Hamadan province, the West of Iran, from April 2008 to September
      2014. In this study, 124 patients with bipolar disorder (both Type I and Type II)
      participated. All patients had experienced 4 relapses. Generalized Estimating
      Equation (GEE) was used to model bipolar disorder episodes, and significance
      level was set at 0.05. Results: The mean (+/-SD) age of the patients was 33.2 (+/
      11.55). Males were more likely to experience mania than depression compared to
      females (odds ratio = 2.30, 95% CI (1.37-3.86)). Patients who received
      psychotherapy plus medicine were less likely to experience mania than depression
      compared to drug receivers (odds ratio = 0.39, 95% CI (0.18-0.88)). In the
      spring, patients were more likely to experience mania than depression compared to
      the winter (OR = 2.22, 95% CI (1.18-4.19)). Conclusion: The results of the
      present study revealed that among bipolar disorder patients in the West of Iran,
      mania was much more prevalent than depression and mixed episodes. Moreover, it
      was found that sex, treatment, and season can determine the episodes of bipolar
      disorder.

PMID- 29062370
TI  - Prevalence of Risky Behaviors and Related Factors among Students of Dezful.
AB  - Objective: There is a likelihood of risky behaviors such as drug abuse, risky
      sexual behavior, and adaptability issues in young ages. The present study aimed
      at investigating the prevalence of risky behaviors among students of Dezful
      University of Medical Sciences in 2014. Method: This was a descriptive-analytical
      cross sectional study, with a random sampling approach. Scale of measuring risky
      behaviors was used to measure the risky behaviors (high speed driving, maim, drug
      use, and sexual behaviors) and related factors. The mean, standard deviation, Chi
      square tests, t tests, and ANOVA were used for data analysis. Results: The study
      was conducted on 150 (50%) female and 150 (50%) male students. Most of the
      participants aged 20 to 24 years. A statistically significant difference was
      obtained between the average scores of risky behaviors among female and male
      students (p?0.05). The results of the present study revealed that the prevalence
      of risky behaviors, high speed driving, and drug consumption was different among
      the students of various study fields (p?0.05). Conclusion: The prevalence of
      risky behaviors among students of Dezful University was relatively low, and the
      prevalence of these behaviors in female students was far less than in male
      students. Risky behaviors were associated with background variables, except for
      mother's occupation.

PMID- 29062371
TI  - Eustress and Malondialdehyde (MDA): Role of Panax Ginseng: Randomized Placebo
      Controlled Study.
AB  - Objective: The present study aimed at evaluating the effect of Panax Ginseng on
      malondialdehyde (MDA) serum levels during eustress on healthy volunteers. Method:
      In this study, 65 healthy volunteers were recruited from students of a medical
      school, with the mean age of 22.61+/-3.63 years. The volunteers were divided into
      2 groups: Group A included 35 participants who were treated by Panax Ginseng 500
      mg/day, which was regarded as the treated group; group B included 30 participants
      treated by placebo 500 mg/day, which was regarded as the control group. Baseline
      data were obtained and then one month after the study, the participants were
      followed with respect to induction of psychological stress through daily
      psychomotor performance task and visual working memory accuracy testing. Stress
      was assessed by malondialdehyde (MDA) serum levels. Results: The participants in
      the control group showed significant increases in MDA serum levels (p = 0.0004),
      which were related to significant increases in perceived stress scale from
      p<0.0001, while Panax Ginseng led to significant reduction in MDA serum levels
      (p<0.01), with significant increase in perceived stress scale (p = 0.02).
      Conclusion: Panax Ginseng produced significant reduction in oxidative stress and
      augmented eustress level in healthy volunteers 1 month after therapy.

PMID- 29062372
TI  - The Relationship between Body Mass Index (BMI) and Depression According to the
      rs16139NPY Gene.
AB  - Objective: Obesity and depression are likely to interact mutually, which makes it
      unclear whether obesity causes depression or depression leads to obesity, and how
      the genotypes have a role in obesity and depression. Method: This cross-
      sectional study was conducted on a sample of 400 individuals from the
      participants in the third phase of the comprehensive Iranian Multicenter
      Osteoporosis Study (IMOS). Anthropometric measurements and depression were
      assessed. PCR-RFLP was used to investigate the NPY polymorphism. Binary logistic
      regression model was employed to determine depression as the dependent factor and
      gene polymorphism. Results: The frequency of NPY rs16139 was 6%. No significant
      association was found between NPY genotypes and depression (p >0.05).
      Furthermore, the results suggest that those with central obesity had an increased
      chance of developing depression (P = 0.02). Conclusion: The frequency of NPY
      polymorphism was 6%. Our study could not find a correlation between rs16139 and
      depression.

PMID- 29062374
TI  - Why Do Emergency Medicine Residents Experience Burn Out? A qualitative study.
AB  - Objective: Emergency medicine residents are a high-risk group for burnout
      syndrome. This was a qualitative study with content analysis on emergency medical
      residents with 2 aims: evaluating the incidence of occupational burnout syndrome
      and identifying the points of view and attitudes of emergency medical residents
      about factors related to occupational burnout syndrome. Method: For this study, 2
      sessions of focus group discussions were set up at Imam Khomeini hospital
      affiliated to Tehran University of Medical Sciences. Each session took 90
      minutes, and 20 emergency medicine residents in their first or second year of
      emergency medicine residency participated in the sessions. Data were coded by
      MAXQDA10 software. Results: Data were categorized in 4 themes as follow: (1) the
      characteristics of emergency medicine; (2) ambiguity in residents' duties; (3)
      educational planning; and (4) careers. Data on the proposed solutions by
      residents were analyzed and coded in 3 groups including (1) changes in personal
      life; (2) arrangement in shifts; and (3) educational issues. Conclusion:
      According to findings of this qualitative study, most of emergency medicine
      residents have experienced exhaustion sometime during the course of their
      residency. Psychological supports may help the residents to cope with their
      career difficulties and probable burn out.

PMID- 29062373
TI  - Comparison of the Effects of Religious Cognitive Behavioral Therapy (RCBT),
      Cognitive Behavioral Therapy (CBT), and Sertraline on Depression and Anxiety in
      Patients after Coronary Artery Bypass Graft Surgery: Study Protocol for a
      Randomized Controlled Trial.
AB  - Objective: The present study aimed at comparing the effects of Religious
      Cognitive Behavioral Therapy (RCBT), Cognitive Behavioral Therapy (CBT), and
      sertraline on depression, anxiety, biomarker levels, and quality of life in
      patients after coronary artery bypass graft (CABG) surgery. Method: This was a
      randomized controlled trial with parallel groups. A total of 160 patients after
      CABG surgery will be screened for anxiety and depression according to clinical
      interviews based on Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV) criteria and Hospital Anxiety Depression Scale (HADS) scores (>=
      8). To assess religious attitude, Golriz and Baraheni's Religious Attitude
      questionnaire will be used. Participants will be randomly allocated to 4 groups
      of 40 including 3 intervention groups (RCBT, CBT, and sertraline) and 1 control
      group (usual care). RCBT and CBT programs will consist of 12 one-hour weekly
      sessions. The participants in the pharmacological intervention group will receive
      25-200 mg/d of sertraline for 3 months. The Short Form-36 Health Survey (SF-36)
      will be administered to assess the patients' quality of life. Blood samples will
      be taken and biomarker levels will be determined using the enzyme-linked
      immunosorbent assay (ELISA). The primary outcome will be reduction in anxiety and
      depression scores after the interventions. The secondary outcomes will be
      increase in quality of life scores and normalized biomarker levels after the
      interventions. Discussion: If RCBT is found to be more effective than the other
      methods; it can be used to improve patients' health status after CABG surgery.
      Irct ID: IRCT201404122898N5.

PMID- 29062375
TI  - A Report of a Novel Mutation in Human Prostacyclin Receptor Gene in Patients
      Affected with Migraine.
AB  - Objective: The human prostacyclin receptor gene encodes the human prostacyclin
      receptor, which is a part of the vasodilator system, during migraine attacks and
      almost certainly plays an important role in the mechanism of this disease.
      Method: The present study aimed at determining any variants in PTGIR gene by
      means of PCR and direct sequencing. Blood samples were taken from the patients,
      and genomic DNA was extracted. Polymerase chain reaction was performed on the
      extracted DNA. The PCR products were then sequenced using the Sanger method.
      Results: When reviewing the familial and clinicopathological history of the 2
      patients, we found that both had symptoms of migraine with visual aura and that
      their mothers were also suffering from migraine. Their parents were not relatives
      prior to marriage. Direct sequencing of Exon 2 of the PTGIR gene showed the
      presence of 2 mutations. These mutations were heterozygous and made the following
      changes: g.1626T>A, c.754T>A, cDNA.867T>A, and p.S252T for the first mutation,
      and c.753C>T, cDNA866C>T, g.1625C>T, and p.C251C for the second mutation. The
      first mutation altered the amino acid and was a novel mutation. The second change
      was a conservative mutation that has already been reported. Conclusion: The
      prediction results of silico studies indicated that the c.754T>A change would
      negatively affect the protein's function and seemed to cause the disease.
      However, functional analysis is required to confirm the association between the
      variant and the disease.

PMID- 29062377
TI  - Determining the Factors Associated with Cardiovascular Disease Recurrence: Tehran
      Lipid and Glucose Study.
AB  - Background: Several studies have emphasized the importance of cardiovascular
      disease (CVD) prevention. However, there is a dearth of data on the prevention of
      cardiovascular disease recurrence. The present study was the 1st in Iran to
      evaluate factors associated with CVD recurrence. Methods: This prospective cohort
      study was conducted on 483 subjects (> 30 years old) with a history of CVD who
      participated in the Tehran Lipid and Glucose Study and were followed up for 12
      years (1999-2012). The relationships between the most important established risk
      factors for CVD and CVD recurrence were evaluated. Results: Totally, 258 (53.4%)
      men and 225(46.5%) women at a mean age of 59.2 +/- 10.7 years were recruited in
      the study. Our results showed that over the 12-year follow-up, the incidence of a
      recurrent event (per 100 person-years) was 48.5. Further, after controlling the
      possible confounding factors, the following variables had a significant
      relationship with CVD recurrence: age (HR = 1.02; p value = 0. 001), male sex (HR
      = 1.4; p value = 0.012), smoking (HR = 1.7; p value = 0.004), and increased
      fasting blood sugar (HR = 2.1; p value = 0.001). Conclusion: We found that the
      established variables in the development of CVD (i.e., age, sex, and smoking)
      played an important role in the risk of CVD recurrence.

PMID- 29062376
TI  - Reduction of Radiation Risk to Interventional Cardiologists and Patients during
      Angiography and Coronary Angioplasty.
AB  - Radiation risk allied to invasive cardiology is relatively high, and protecting
      both patients and cardiologists is necessary. The aim of this review is to
      discuss how to better protect patients and cardiologists against radiation
      exposure. We performed a global search on PubMed, Science Direct, and Scopus
      databases via keywords of "interventional cardiologist", "patient", "radiation",
      and "exposure" and then performed an overview of the main strategies for risk
      reduction among interventional cardiologists and exposed patients. The 1st line
      for protection is awareness of both radiation risk factors and exposure doses and
      how to manage and minimize exposure levels. In conclusion, radiation-attenuating
      techniques can effectively reduce occupational/treatment radiation exposure to
      both operators and patients in cardiology interventions.

PMID- 29062378
TI  - Association between rs10757274 and rs2383206 SNPs as Genetic Risk Factors in
      Iranian Patients with Coronary Artery Disease.
AB  - Background: There are only a few reports concerning the genetic risk factors for
      coronary artery disease (CAD). However, 2 polymorphisms of rs10757274 and
      rs2383206 on chromosome 9p21.3 have been shown recently to be associated with CAD
      in certain populations. This is the 1st study to investigate their validity and
      association with CAD in a sample of the Iranian population. Methods: Genomic DNA
      was extracted from the peripheral blood of all participants, consisting of 111
      cases with CAD and 100 normal controls with normal coronary angiographies.
      Genotyping of rs10757274 and rs2383206 was performed in the cases and controls
      using designed mismatch primers via the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. Results: Statistical analysis
      presented a significant association between the rs10757274 GG (p value = 0.029,
      chi2 = 7.078) and rs2383206 GG (p value = 0.036, chi2 =6.658) genotypes and CAD
      among the cases as compared with the normal controls. Haplotype analysis of
      rs10757274 and rs2383206 polymorphisms showed 43% GG/GG haplotype with a
      significant association with CAD (p value = 0.014, chi2 = 6.058). Conclusion: The
      results of this study provide an insight into the underlying molecular mechanism
      of CAD pathogenesis and pave the way for future functional studies on these
      variants.

PMID- 29062380
TI  - Anomalous Left Coronary Artery from the Pulmonary Artery Presenting with Atypical
      Chest Pain in an Adult: A Case Report.
AB  - The anomalous origin of the left coronary artery from the pulmonary artery
      (ALCAPA) is a rare congenital anomaly. The usual clinical course is severe left
      sided heart failure and mitral valve insufficiency presenting during the first
      months of life. However, in some cases, the collateral blood supply from the
      right coronary artery is sufficient and symptoms may be subtle or even absent. We
      describe a 49-year-old woman presenting with atypical chest pain during physical
      exertion. The exercise tolerance test and then coronary angiography by indication
      revealed an anomalous origin of the left coronary artery. The patient underwent
      surgical treatment, whereby a pulmonary artery tube graft from the aorta to the
      left coronary artery was created and the main pulmonary artery was reconstructed
      with a bovine pericardial patch. The patient was discharged from the hospital
      without any chest pain and dyspnea and was symptom free during a follow-up period
      of 18 months. Clinicians should consider ALCAPA as a differential diagnosis in
      adults with presentations similar to exercise-related asthma.

PMID- 29062379
TI  - Association between the Hepatic Lipase Promoter Region Polymorphism (-514 C/T)
      and the Presence and Severity of Premature Coronary Artery Disease.
AB  - Background: Hepatic lipase (HL) plays a crucial role in lipid metabolism, but
      there is debate about whether HL acts in a more pro- or more anti-atherogenic
      fashion. We aimed to examine the relationship between the -514 C/T polymorphism
      within the HL gene (LIPC) and the risk of angiographically determined premature
      coronary artery disease (CAD). Methods: Four hundred seventy-one patients with
      newly diagnosed angiographically documented (>= 50% luminal stenosis of any
      coronary vessel) premature CAD were compared to 503 controls (subjects with no
      luminal stenosis in coronary arteries). A real-time polymerase chain reaction and
      high-resolution melting analysis was used to distinguish between the genotypes.
      Results: There was no significant difference in the distribution of -514 C/T
      genotypes between the 2 groups in the whole population or in the men, but the
      examined polymorphism was found to be associated with the presence of CAD in the
      women (p value = 0.029). After the application of a multiple logistic regression
      model, the minor T allele of the LIPC gene was not found to be independently
      associated with the presence of CAD either in the total population (adjusted OR =
      0.97, 95% CI = 0.75-1.25; p value = 0.807) or in the women (adjusted OR = 0.91,
      95% CI = 0.59-1.40; p value = 0.650) and in the men (adjusted OR = 1.15, 95% CI =
      0.81-1.64; p value = 0.437) separately. Conclusion: Our findings suggest that
      there is no relationship between the LIPC -514 C/T and the risk of premature CAD
      or its severity in patients undergoing coronary angiography.

PMID- 29062381
TI  - A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month
      Old Infant.
AB  - The VACTERL association, co-occurrence of vertebral, anorectal, cardiac,
      tracheoesophageal, genitourinary, and limb malformations, is a rare congenital
      anomaly. Several cardiac anomalies have been reported as a part of the VACTERL
      association, particularly ventricular and atrial septal defects. Pulmonary artery
      sling is a rare congenital abnormality in which the left pulmonary artery arises
      from the right pulmonary artery. This anomaly is not frequently observed in the
      VACTERL association and has been rarely reported. A 20-month-old girl was
      admitted to our hospital due to pneumonia in the right lung, which had pulmonary
      artery sling as a part of the VACTERL association. Barium meal X-ray showed
      pressure effects on the esophagus, and computed tomography angiography revealed
      pulmonary artery sling. Pneumonia management was done. However, the parents of
      our patient refused to give consent for the surgical correction of this vascular
      anomaly. Three months after discharge from the hospital, the patient was visited,
      at which time the parents again refused surgery and treatment for their daughter
      despite our recommendations.

PMID- 29062382
TI  - Novel Treatment Approach to Ascending Aorta Pseudoaneurysms: A Case Report.
AB  - The pseudoaneurysm of the aorta is rarely due to trauma and infection but usually
      is a late complication of previous surgical procedures like coronary artery
      bypass graft surgery. We describe a 65-year-old woman with the pseudoaneurysm of
      the ascending aorta due to coronary artery bypass graft surgery. It was revealed
      in coronary artery angiography after nonspecific symptoms. It was confirmed by
      multidetector computed tomographic angiography. The patient refused open cardiac
      surgery, so we decided to use an atrial septal defect occluder device in off
      label way to seal the pseudoaneurysm orifice. In a hybrid operating room setting,
      the procedure was done successfully and patient's hospitalization course was
      eventless. In multidetector computed tomographic angiography after 3 months, the
      device was in the appropriate position without endoleak and in the yearly visit
      the patient was asymptomatic and healthy.

PMID- 29062383
TI  - Perventricular Muscular Ventricular Septal Defect (VSD) Closure under Epicardial
      Echocardiography Guidance: A Case Report.
AB  - Ventricular septal defects (VSDs) are among the most common congenital cardiac
      lesions. Large defects at apicomuscular regions, especially in young patients,
      are far from accessible to surgeons for conventional surgery. Moreover, the
      transcatheter closure of VSDs in these patients is difficult and carries a high
      risk of complications because of the large sheath size relative to the patient's
      size. The periventricular approach simplifies VSD closure and, thus, eliminates
      the potential complications of cardiac catheterization and fluoroscopy as it is
      performed under echocardiographic guidance. A 3-year-old girl with a body weight
      of 11 kg (failure to thrive) was referred to us. She had multiple adjacent
      apicomuscular VSDs, the largest one being about 19 mm in diameter, and
      subsystemic pulmonary artery pressure (PAP). The patient underwent
      periventricular apicomuscular VSD closure with a Lifetech muscular VSD occluder
      (size 22 mm) under epicardial echocardiography guidance without cardiopulmonary
      bypass. Post procedure, the PAP was decreased to mild level. The residual shunt
      was mild across the adjacent small defects. She was discharged after 7 days
      without complications. At 2 years' follow-up, the patient was hemodynamically
      stable and had a normal PAP (PAP = about 16 mmHg) by transthoracic
      echocardiographic assessment.

PMID- 29062384
TI  - Asymptomatic Giant Lipoma of the Right Ventricular Outflow Tract: A Case Report.
AB  - Cardiac lipomas are extremely rare tumors of the heart. They are usually
      symptomatic and rarely may be found incidentally in autopsies. Here we describe a
      23-year-old healthy man, in whose physical examination for employment a murmur
      was found incidentally. Transthoracic and then transesophageal echocardiographic
      examination showed a 4-cm oval-shaped mass in the right ventricular outflow
      tract. He underwent elective surgery, during which the tumor was removed under
      cardiopulmonary bypass and aortic-cross clamping via right atriotomy. The
      postoperative course was uneventful, and the patient was in good condition at 1
      year's follow-up.

PMID- 29062385
TI  - Central Nervous System and Limb Embolism Concurrence due to Atrial Myxoma: A Case
      Report?.
AB  - Cardiac myxomas are the most common cardiac tumors with diverse nonspecific
      clinical manifestations. A 78-year-old man presented to the emergency department
      with complaints of pain and coldness of the left lower extremity. The left
      femoral artery pulse was detected, while the pulses of the left popliteal,
      dorsalis pedis, and posterior tibialis arteries were absent. No blood inflow was
      detected in the superficial and deep femoral, popliteal, and anterior and
      posterior tibialis arteries. Thrombectomy was performed, and a fatty-like mass
      from the bifurcation of the common femoral artery and a thrombotic mass from the
      proximal portion of the superficial and deep femoral arteries were removed. The
      pulsatile inflow and palpable pulses of the left femoral, popliteal, dorsalis
      pedis, and posterior tibialis arteries were restored after surgery. The
      histological findings of the embolus were suggestive of a cardiac myxoma. The
      patient's consciousness and lower limb blood flow improved gradually. He was
      discharged from the hospital with full awareness and improved lower extremity
      muscle function 2 weeks after surgery.

PMID- 29062387
TI  - Limitations of workers diagnosed with cancer evaluated with Work Role Functioning
      Questionnaire-Br.
AB  - The main subject of the current study is to look into the limitations found in
      individuals diagnosed with cancer, considered a public health problem, especially
      in developing countries where the impact of this disease is expected to account
      for 80% of 20 million new cases estimated worldwide by 2025. For some patients
      undergoing treatment, continuing to be professionally active is challenging
      especially considering that work fosters a purpose in life, a sense of
      contribution, distraction, and self-esteem, which aids in physical, cognitive,
      emotional, and interpersonal recovery. Within this context, the aim is to
      describe the limitations found in individuals with cancer, who have maintained
      their work activities in private service during radiotherapy treatment, through a
      descriptive study and a quantitative approach. The final sample of 51
      participants was defined by non-probability convenience sampling, based on
      information from all patients admitted in that period, with a research protocol
      approved by the Research Ethics Committee. The assessment using the Brazilian
      version of the Work Role Functioning Questionnaire showed higher average work
      functioning indexes for social demand, with an average score of 94.33 (11.47). In
      turn, the worst indexes were registered in physical demand. No significant
      differences were observed between groups of treatment protocols in terms of WRFQ
      Br scores. The work functioning assessment of workers diagnosed with cancer in
      radiotherapy using the WRFQ-Br showed higher scores for social demands and lower
      for physical demands. The preserved social performance may be linked to
      individual work functioning within the family, at work and, consequently, within
      society, given that the study included patients who maintained their work
      activities during the proposed treatment period, highlighting the social role of
      work for patients with cancer.

PMID- 29062388
TI  - Highlights from the WIN 2017 Symposium, 26-27 June 2017, Paris, France:
      'Expediting Global Innovation in Precision Cancer Medicine'.
AB  - The Worldwide Innovative Networking (WIN) symposium brings together
      representatives from academic institutions, pharmaceutical partners, technology
      companies and charitable organisations from across the globe for an annual
      summit, discussing ongoing research and the latest developments in precision
      medicine. Now, in its seventh year, the aims of the WIN consortium's annual
      meeting, to foster communication and collaboration between members and deliver
      clinical trial results that improve the care and outcomes of patients are
      presented in open dialogue to encourage debate and discussion. This year, the
      meeting was held in Paris, France from 26-27 June and consisted of six plenary
      sessions, two debates, and poster presentations from attendees. In keeping with
      the consortium's goals, presentations and posters focused on the development and
      integration of new therapies and updates in genome-based medicine. Among the
      presentations at this year's meeting, much of the focus fell on design and
      implementation of new designs of clinical trials, moving away from decades-long
      assessments of thousands of patients towards a nimble, adaptive design fitting
      the edicts of personalised medicine and delving into greater depths within
      genomic data, ranging beyond genome analysis to chart new targets in ligandomics,
      proteogenomics and more.

PMID- 29062390
TI  - Designing a Biostable L-DNAzyme for Lead(II) Ion Detection in Practical Samples.
AB  - A promising biosensor for effectively lead (II) ion detection in practical
      applications was developed by constructing a Pb2+-specific L-DNAzyme, the
      enantiomer of the natural nucleic acid-constructed D-DNAzyme. This fluorescent
      sensor contains the L-enzyme strand with a quencher at the 3' end, and the L
      substrate strand with a fluorophore at the 5' and a quencher at the 3' ends that
      formed a complex. In the presence of Pb2+, the L-substrate is cut into two
      fragments, leading to the recovery of fluorescence. The sensor shows high
      sensitivity and selectivity for Pb2+ detection with a linear response in the
      range of 5-100 nM and a detection limit of 3 nM in aqueous solution. Importantly,
      based on that L-DNAzyme consists of non-natural nucleic acids, which is
      insensitive to nuclease digestion, protein adsorption and D-DNA hybridization,
      our sensor shows specific response to Pb2+ in practical water and serum samples.
      Therefore, it is expected that our L-DNAzyme-based strategy may offer a new
      method for developing simple, rapid and sensitive sensors in complex systems.

PMID- 29062389
TI  - Use of PEG-asparaginase in monomorphic epitheliotropic intestinal T-cell
      lymphoma, a disease with diagnostic and therapeutic challenges.
AB  - Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known
      as enteropathy associated T-cell lymphoma (EATL) type II, is a rare
      haematological malignancy with a difficult and delayed diagnosis. Symptoms can
      include abdominal pain, weight loss, and chronic diarrhoea. However, most
      patients are only diagnosed after complications, such as perforation or
      obstruction, have developed. There is no standard treatment for MEITL; most
      accepted regimens consist of surgical resection and anthracycline-based
      chemotherapy. Prognosis is poor with an approximate survival of less than a year.
      Even though other therapies, such as autologous stem cell transplant, has shown
      promising results, not all patients can tolerate this course of treatment
      especially if they are elderly, have several comorbidities or are malnourished.
      Innovative therapies that improve survival and can be used as an alternative for
      more intensive treatment are needed. We report the use of PEG-asparaginase along
      with conventional anthracycline therapy in a 70-year-old woman diagnosed with
      MEITL, who went into remission and survived for more than one year before
      succumbing to relapsed disease.

PMID- 29062386
TI  - Proteins regulating the intercellular transfer and function of P-glycoprotein in
      multidrug-resistant cancer.
AB  - Chemotherapy is an essential part of anticancer treatment. However, the
      overexpression of P-glycoprotein (P-gp) and the subsequent emergence of multidrug
      resistance (MDR) hampers successful treatment clinically. P-gp is a multidrug
      efflux transporter that functions to protect cells from xenobiotics by exporting
      them out from the plasma membrane to the extracellular space. P-gp inhibitors
      have been developed in an attempt to overcome P-gp-mediated MDR; however, lack of
      specificity and dose limiting toxicity have limited their effectiveness
      clinically. Recent studies report on accessory proteins that either directly or
      indirectly regulate P-gp expression and function and which are necessary for the
      establishment of the functional phenotype in cancer cells. This review discusses
      the role of these proteins, some of which have been recently proposed to comprise
      an interactive complex, and discusses their contribution towards MDR. We also
      discuss the role of other pathways and proteins in regulating P-gp expression in
      cells. The potential for these proteins as novel therapeutic targets provides new
      opportunities to circumvent MDR clinically.

PMID- 29062392
TI  - Jurisdiction of the Medical Ethics Committees.
AB  - Ethical principles of assessing medical research are to the greatest extent
      defined by the Nuremberg Code, the Declarations of Geneva and Helsinki, and the
      Oviedo Convention. Pursuant to their directives various national Medical Ethics
      Committees (MECs) were established which assess the ethics of research according
      to the risk and benefit ratio of the persons involved. Following the example of
      other countries, medical ethics committees eventually appeared also in hospitals
      and some medical and educational institutions around Slovenia. Due to an
      increased number of ethical challenges, it is of great importance to define the
      jurisdiction of the Slovenian MECs in order to ensure their coordinated
      operation. Exclusive jurisdiction of the national MEC includes multicentre and
      multi-national research, drug research (phases 1-3), high-risk research and
      research related to doctoral theses. The jurisdiction of the sectoral MECs
      includes testing the conditions for research, monitoring the execution and
      overviewing the final reports. A more significant jurisdiction of the sectoral
      MEC is preserving an ethical environment in their institutions. A network of
      Slovenian MECs is to be organised in the form of a jurisdiction pyramid where
      each member has its own obligations and responsibilities and plays an important
      role in relation to the entire structure.

PMID- 29062391
TI  - Metabolic Comparison of Dorsal versus Ventral Cells Directly in the Live 8-cell
      Frog Embryo by Microprobe Single-cell CE-ESI-MS.
AB  - Single-cell mass spectrometry (MS) empowers the characterization of metabolomic
      changes as cells differentiate to different tissues during early embryogenesis.
      Using whole-cell dissection and capillary electrophoresis electrospray ionization
      (CE-ESI) MS, we recently uncovered metabolic cell-to-cell differences in the 8-
      and 16-cell embryo of the South African clawed frog (Xenopus laevis), raising the
      question whether metabolic cell heterogeneity is also detectable across the
      dorsal-ventral axis of the 8-cell embryo. Here, we tested this hypothesis
      directly in the live embryo by quantifying single-cell metabolism between the
      left dorsal-animal (D1L) and left ventral-animal (V1L) cell pairs in the same
      embryo using microprobe single-cell CE-ESI-MS in the positive ion mode. After
      quantifying ~70 molecular features, including 52 identified metabolites, that
      were reproducibly detected in both cells among n = 5 different embryos, we
      employed supervised multivariate data analysis based on partial least squares
      discriminant analysis (PLSDA) to compare metabolism between the cell types.
      Statistical analysis revealed that asparagine, glycine betaine, and a yet
      unidentified molecule were statistically significantly enriched in the D1L cell
      compared to V1L (p < 0.05 and fold change >= 1.5). These results demonstrate that
      cells derived from the same hemisphere (animal pole) harbor different metabolic
      activity along the dorsal-ventral axis as early as the 8-cell stage. Apart from
      providing new evidence of metabolic cell heterogeneity during early
      embryogenesis, this study demonstrates that microprobe single-cell CE-ESI-MS
      enables the analysis of multiple single cells in the same live vertebrate embryo.

PMID- 29062393
TI  - Running Injuries in the Participants of Ljubljana Marathon.
AB  - INTRODUCTION: The aim of our study was to determine the self-reported incidence
      and prevalence of running-related injuries among participants of the 18th
      Ljubljana Marathon, and to identify risk factors for their occurrence. METHODS: A
      customized questionnaire was distributed over registration. Independent samples
      of t-test and chi-square test were used to calculate the differences in risk
      factors occurrence in the injured and non-injured group. Factors which appeared
      significantly more frequently in the injured group were included further into
      multiple logistic regression analysis. RESULTS: The reported lifetime running
      injury (absence >2 weeks) incidence was: 46% none, 47% rarely, 4% occasionally,
      and 2% often. Most commonly injured body regions were: knee (30%), ankle and
      Achilles' tendon (24%), foot (15%), and calf (12%). Male gender, running history
      of 1-3 years, and history of previous injuries were risk factors for life-time
      running injury. In the season preceding the event, 65% of participants had not
      experienced any running injuries, 19% of them reported minor problems (max 2
      weeks absenteeism), but 10% and 7% suffered from moderate (absence 3-4 weeks) or
      major (more than 4 weeks pause) injuries. BMI was identified as the solely risk
      factor. CONCLUSIONS: This self-reported study revealed a 53% lifetime prevalence
      of running-related injuries, with the predominate involvement of knee, ankle and
      Achilles' tendon. One out of three recreational runners experienced at least one
      minor running injury per season. It seems that male gender, short running
      experience, previous injury, and BMI do increase the probability for running
      related injuries.

PMID- 29062394
TI  - Patient Safety Culture in Slovenian out-of-hours Primary Care Clinics.
AB  - INTRODUCTION: Patient safety culture is a concept which describes how leader and
      staff interaction, attitudes, routines and practices protect patients from
      adverse events in healthcare. We aimed to investigate patient safety culture in
      Slovenian out-of-hours health care (OOHC) clinics, and determine the possible
      factors that might be associated with it. METHODS: This was a cross-sectional
      study, which took place in Slovenian OOHC, as part of the international study
      entitled Patient Safety Culture in European Out-of-Hours Services (SAFE-EUR-OOH).
      All the OOHC clinics in Slovenia (N=60) were invited to participate, and 37
      agreed to do so; 438 employees from these clinics were invited to participate. We
      used the Slovenian version of the Safety Attitudes Questionnaire - an ambulatory
      version (SAQAV) to measure the climate of safety. RESULTS: Out of 438 invited
      participants, 250 answered the questionnaire (57.1% response rate). The mean
      overall score +/- standard deviation of the SAQ was 56.6+/-16.0 points, of
      Perceptions of Management 53.6+/-19.6 points, of Job Satisfaction 48.5+/-18.3
      points, of Safety Climate 59.1+/-22.1 points, of Teamwork Climate 72.7+/-16.6,
      and of Communication 51.5+/-23.4 points. Employees working in the Ravne na
      Koroskem region, employees with variable work shifts, and those with full-time
      jobs scored significantly higher on the SAQ-AV. CONCLUSION: The safety culture in
      Slovenian OOHC clinics needs improvement. The variations in the safety culture
      factor scores in Slovenian OOHC clinics point to the need to eliminate variations
      and improve working conditions in Slovenian OOHC clinics.

PMID- 29062395
TI  - Implementing Quality Indicators for Diabetes and Hypertension in Family Medicine
      in Slovenia.
AB  - INTRODUCTION: A new form of family practices was introduced in 2011 through a
      pilot project introducing nurse practitioners as members of team and determining
      a set of quality indicators. The aim of this article was to assess the quality of
      diabetes and hypertension management. METHODS: We included all family medicine
      practices that were participating in the project in December 2015 (N=584). The
      following data were extracted from automatic electronic reports on quality
      indicators: gender and specialisation of the family physician, status (public
      servant/self-contracted), duration of participation in the project, region of
      Slovenia, the number of inhabitants covered by a family medicine practice, the
      name of IT provider, and levels of selected quality indicators. RESULTS: Out of
      584 family medicine practices that were included in this project at the end of
      2015, 568 (97.3%) had complete data and could be included in this analysis. The
      highest values were observed for structure quality indicator (list of diabetics)
      and the lowest for process and outcome quality indicators. The values of the
      selected quality indicators were independently associated with the duration of
      participation in the project, some regions of Slovenia where practices were
      located, and some IT providers of the practices. CONCLUSION: First, the analysis
      of data on quality indicators for diabetes and hypertension in this primary care
      project pointed out the problems which are currently preventing higher quality of
      chronic patient management at the primary health care level.

PMID- 29062396
TI  - The Role of Health Services in Encouraging Disclosure of Violence Against Women.
AB  - INTRODUCTION: The aim of the survey was to assess the differences in disclosure
      by the type of violence to better plan the role of health services in identifying
      and disclosing violence. METHODS: A validated, anonymous screening questionnaire
      (NorAQ) for the identification of female victims of violence was offered to all
      postpartum women at a single maternity unit over a three-month period in 2014.
      Response rate was 80% (1018 respondents). Chi square test was used for
      statistical analysis (p<0.05 significant). RESULTS: There are differences in
      disclosure by type of violence. Nearly half (41.5%) of violence by health care
      services was not reported, compared to 33.7% physical, 23.4% psychological, and
      32.5% sexual that was reported. The percentage of violence in intimate
      partnership reported to health care staff is low (9.3% to 20.8%), but almost half
      of the violence experienced by heath care services (44%) is reported. Intimate
      partnership violence is more often reported to the physician than to the
      psychologist or social worker. Violence in health care service is reported also
      to nurses. CONCLUSIONS: Disclosure enables various institutions to start with the
      procedures aimed at protecting victims against violence. Health workers should
      continuously encourage women to speak about violence rather than asking about it
      only once. It is also important that such inquiries are made on different levels
      of health care system and by different health care professions, since there are
      differences to whom women are willing to disclose violence.

PMID- 29062397
TI  - Key Factors Determining Indoor Air PM10 Concentrations in Naturally Ventilated
      Primary Schools in Belgrade, Serbia.
AB  - INTRODUCTION: Indoor air quality (IAQ) is rated as a serious public health issue.
      Knowing children are accounted as more vulnerable to environmental health
      hazards, data are needed on air quality in schools. METHODS: A project was
      conducted from 2007 until 2009 (SEARCH, School Environment and Respiratory Health
      of Children), aiming to verify links between IAQ and children's respiratory
      health. Study was conducted in ten primary schools on 735 children, in 44
      classrooms. Children were randomly selected. Research tools and indicators used
      for children's exposure to school environment were indoor and outdoor pollutants,
      two standardized questionnaires for school and classroom characteristics. In both
      classroom air and ambient air in front of them we measured, during a 5-day
      exposure period for continuous 24h measuring: carbon monoxide, carbon dioxide,
      indoor air temperature, relative humidity, and PM10 during classes. RESULTS: PM10
      concentrations were significantly most frequent in an interval of >=80.1MUg/m3,
      that is, in the interval above 50MUg/m3. Mean PM10 value was 82.24+/-42.43
      MUg/m3, ranging from 32.00MUg/m3 to of 197.00MUg/m3. CONCLUSION: The increase of
      outdoor PM10 concentration significantly affects the increase of indoor PM10. A
      statistically significant difference exists for average IAQ PM10 concentrations
      vs. indicators of indoor thermal comfort zone (p<0.0001); they are lower in the
      classrooms with indicators within the comfort zone. Moreover, dominant factors
      for the increase of PM10 are: high occupancy rate in the classroom (<2m2 of space
      per child), high relative humidity (>75%), and indoor temperature beyond 23
      degrees C, as well as bad ventilation habits (keeping windows shut most of the
      time).

PMID- 29062398
TI  - Clinical Profile and Management of Patients with Incident and Recurrent Acute
      Myocardial Infarction in Albania - a Call for More Focus on Prevention
      Strategies.
AB  - BACKGROUND: The clinical profile of acute myocardial infarction (AMI) patients
      reflects the burden of risk factors in the general population. Differences
      between incident (first) and recurrent (repeated) events and their impact on
      treatment are poorly described. We studied potential differences in the clinical
      profile and in-hospital treatment between patients hospitalised with an incident
      and recurrent AMI. METHODS: A total of 324 patients admitted in the Coronary Care
      Unit of 'Mother Teresa' hospital, Tirana, Albania (2013-2014), were included in
      the study. Information on AMI type, complications and risk factors was obtained
      from patient's medical file. Logistic regression analyses were used to explore
      differences between the incident and recurrent AMIs regarding clinical profile
      and in-hospital treatment. RESULTS: Of all patients, 50 (15.4%) had a prior AMI.
      Compared to incident cases, recurrent cases were older (P=0.01), more often women
      (P=0.01), less educated (P=0.01), and smoked less (P=0.03). Recurrent cases
      experienced more often heart failure (HF) (OR=2.48; 95% CI: 1.31-4.70), impaired
      left ventricular ejection fraction (OR=1.97; 95% CI:1.05-3.71), and multivessel
      disease (OR=6.32; 95% CI: 1.43-28.03) than incident cases. In-hospital use of
      beta-blockers was less frequent among recurrent compared to incident cases
      (OR=0.45; 95% CI: 0.24-0.85), while no statistically significant differences
      between groups were observed regarding angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker, statin, aspirin or invasive procedures.
      CONCLUSION: A more severe clinical expression of the disease and underutilisation
      of treatment among recurrent AMIs are likely to explain their poorer prognosis
      compared to incident AMIs.

PMID- 29062399
TI  - Self-reported Hypoglycaemia in Patients treated with Insulin: A Large Slovenian
      Retrospectively-prospective Study.
AB  - INTRODUCTION: Hypoglycaemia is the major barrier for glycaemic target achievement
      in patients treated with insulin. The aim of the present study was to investigate
      real-world incidence and predictors of hypoglycaemia in insulin-treated patients.
      METHODS: More than 300 consecutive patients with type 1 or type 2 diabetes
      treated with insulin were enrolled during regular out-patient visits from 36
      diabetes practices throughout the whole country. They completed a comprehensive
      questionnaire on hypoglycaemia knowledge, awareness, and incidence in the last
      month and last six months. In addition, in the prospective part, patients
      recorded incidence of hypoglycaemic events using a special diary prospectively on
      a daily basis, through 4 weeks. RESULTS: At least one hypoglycaemic event was
      self-reported in 84.1%, and 56.4% of patients with type 1 and type 2 diabetes,
      respectively, during the prospective period of 4 weeks. 43.4% and 26.2% of
      patients with type 1 and type 2 diabetes, respectively, experienced a nocturnal
      hypoglycaemic event. In the same time-period, severe hypoglycaemia was
      experienced by 15.9% and 7.1% of patients with type 1 and type 2 diabetes,
      respectively. Lower glycated haemoglobin was not a significant predictor of
      hypoglycaemia. CONCLUSIONS: Rates of self-reported hypoglycaemia in patients
      treated with insulin in the largest and most comprehensive study in Slovenia so
      far are higher than reported from randomised control trials, but comparable to
      data from observational studies. Hypoglycaemia incidence was high even with high
      glycated haemoglobin values.

PMID- 29062400
TI  - Self- Perceived Stress in Relation to Anxiety, Depression and Health-related
      Quality of Life among Health Professions Students: A Cross-sectional Study from
      Bosnia and Herzegovina.
AB  - INTRODUCTION: The purpose of the present study was to examine self-perceived
      stress of health professions students at the Faculty of Medicine Foca, and to
      explore its association with anxiety, depression and health-related quality of
      life. METHODS: The cross-sectional study enrolled 451 students at the Faculty of
      Medicine (medicine, dentistry, nursing and speech therapy). Survey instruments
      were distributed at the conclusion of the spring semester during the last
      required lecture for each year and study programme class. Perceived stress was
      assessed using the 14-item Perceived Stress Scale. The students were evaluated
      for symptoms of depression and anxiety, using Zung's self-assessment inventory
      for depression and the Spielberger State-Trait Anxiety Inventory (STAI). European
      Quality of Life-5 dimensions were used for describing and evaluating health.
      Multivariate analyses were carried out using logistic regression to examine the
      relationship between the outcome variable and selected determinant factors.
      RESULTS: A high degree of stress was reported by 1.6% of students, while the
      majority of students had either moderate (70.6%) or low degree (27.5%) of stress.
      The significant independent factors associated with perceived stress were anxiety
      score (OR, 0.339; CI 95%, 0.276-0.403) and EQ-5D score (OR, 0.044; CI 95%, 0.033
      0.085). A high degree of perceived stress (OR, 0.624; CI 95%, 0.507-0.704), the
      presence of depression (OR, 0.800; CI 95%, 0.513-1.087), and low quality of life
      were associated with anxiety (OR, 0.073; CI 95%, 0.018-0.128). CONCLUSION: Higher
      levels of perceived stress predispose health professions students for anxiety and
      lower quality of life. The study programme was not a significant determinant of
      perceived stress sore.

PMID- 29062401
TI  - Validation of The Slovenian Version of Multiple Sclerosis Quality of Life (MSQOL
      54) Instrument.
AB  - PURPOSE: To cross-culturally adapt and validate Multiple Sclerosis Quality of
      Life-54 (MSQOL-54) instrument. METHODS: The study which enrolled 134 Slovenian
      multiple sclerosis (MS) patients was conducted from March to December 2013. The
      internal consistency of the MSQOL-54 instrument was evaluated by Cronbach's alpha
      coefficient (alpha), and its dimensionality assessed by the principal component
      analysis (PCA). RESULTS: The whole instrument had high internal consistency
      (alpha=0.88), as well as the majority of its twelve subscales (alpha=0.83-0.94).
      The results of the PCA showed two components with eigenvalue greater than 1,
      explaining 59.4% of the cumulative variance. Further results indicated good
      construct validity of the instrument with the physical health-related-quality-of
      life subscales loading highly on the physical component, and mental health
      related-quality-of-life subscales loading highly on the mental component.
      CONCLUSION: The Slovenian version of the MSQOL-54 instrument proved to be an
      internally consistent and accurate tool, well accepted by the Slovenian MS
      patients. The adequate psychometric properties warrant the scientifically sound
      version of the MSQOL-54 instrument, which is from now on at disposal to all
      health professionals dealing with MS patients in Slovenia.

PMID- 29062403
TI  - Solvent-free sonochemistry: Sonochemical organic synthesis in the absence of a
      liquid medium.
AB  - Sonochemistry, i.e., the application of mechanical energy in the form of sound
      waves, has recently been recognised for its similarity to mechanochemistry and is
      now included under the umbrella term of mechanochemistry. Typically, due to the
      hypothesised cavitation mechanism, a liquid medium is considered as a necessity
      for a process to take place as a result of ultrasonic irradiation. In view of
      this, condensation reactions between solid reagents in the complete absence of
      solvent were carried out successfully by ultrasonic irradiation with the
      importance of particle size being highlighted. This work increases the potential
      of sonochemistry in the drive towards a sustainable future.

PMID- 29062402
TI  - The Outcomes of Pregnancy and Childbirth in Adolescents in Slovenia.
AB  - INTRODUCTION: The objective of the study was to determine the course and outcomes
      of pregnancy and childbirth in adolescents compared to women aged 20-24 years in
      Slovenia. METHODS: In the retrospective study, the course of pregnancy and labour
      and the perinatal outcome of newborns in primiparous adolescents aged <=19 years
      (study group) have been compared to the control group of primiparous women aged
      20-24 years. The study group was further divided into a study subgroup of
      adolescents aged <=17 years. Data were retrieved from the National Perinatal
      Information System in Slovenia for the period 2008-2012. Altogether, 13,663 women
      and their newborns were included. RESULTS: Adolescent pregnancy was associated
      with increased rates of unknown estimated date of delivery, preterm labour, low
      birth weight newborns, small for gestational age newborns and low gestational
      weight gain. Spontaneous labour was more common in adolescents, while emergency
      and elective Caesarean sections were less common than in women aged 20-24 years.
      In addition, pregnancy in adolescents aged <=17 years was associated with
      increased rate of maternal anaemia and labour without complications. Higher rates
      of smoking, lower rates of parenting school attendance, lower rates of pregnancy
      check-ups and screening tests in pregnancy such as nuchal translucency in
      adolescents were found. CONCLUSIONS: The results of the study show that
      adolescent pregnancy is related to higher health risks for pregnant adolescents
      and their newborns. In addition, adolescents are subject to poorer prenatal care
      comparing to older women.

PMID- 29062404
TI  - Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C-
      and S-glycosides.
AB  - Carbohydrate related enzymes, like glycosyltransferases and glycoside hydrolases,
      are nowadays more easily accessible and are thought to represent powerful and
      greener alternatives to conventional chemical glycosylation procedures. The
      knowledge of their corresponding mechanisms has already allowed the development
      of efficient biocatalysed syntheses of complex O-glycosides. These enzymes can
      also now be applied to the formation of rare or unnatural glycosidic linkages.

PMID- 29062405
TI  - Synthesis of benzothiophene and indole derivatives through metal-free propargyl
      allene rearrangement and allyl migration.
AB  - An efficient base-catalyzed protocol for the synthesis of benzothiophene is
      described. The reaction proceeds via base-promoted propargyl-allenyl
      rearrangement followed by cyclization and allyl migration. Phosphine-substituted
      indoles can be synthesized by a similar strategy.

PMID- 29062406
TI  - Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz
      Fritsch-Bobbitt reaction with non-activated and moderately-activated systems.
AB  - Background: 1,2,3,4-Tetrahydroisoquinolines (THIQs) are common motifs in
      alkaloids and in medicinal chemistry. Synthetic access to THIQs via the Pomeranz
      Fritsch-Bobbit (PFB) methodology using mineral acids for deactivated, electron
      poor aromatic systems, is scarcely represented in the literature. Here, the
      factors controlling the regiochemical outcome of cyclization are evaluated.
      Results: A double reductive alkylation was telescoped into a one-pot reaction
      delivering good to excellent yields of desired aminoacetals for cyclization.
      Cyclization of activated systems proceeded smoothly under standard PFB
      conditions, but for non-activated systems the use of HClO4 alone was effective.
      When cyclization was possible in both para- and ortho-positions to the
      substituent, 7-substituted derivatives were formed with significant amounts of 5
      substituted byproduct. The formation of the 4-hydroxy-THIQs vs the 4-methoxy-THIQ
      products could be controlled through modification of the reaction concentration.
      In addition, while a highly-activated system exclusively cyclized to the indole,
      this seems generally highly disfavored. When competition between 6- and 7-ring
      formation was investigated in non-activated systems, 5,7,8,13-tetrahydro-6,13
      methanodibenzo[c,f]azonine was exclusively obtained. Furthermore, selective ring
      closure in the para-position could be achieved under standard PFB conditions,
      while a double ring closure could be obtained utilizing HClO4. Conclusion:
      Reactivity differences in aminoacetal precursors can be employed to control
      cyclization using the PFB methodology. It is now possible to select confidently
      the right conditions for the synthesis of N-aryl-4-hydroxy-1,2,3,4
      tetrahydroisoquinolines.

PMID- 29062407
TI  - beta-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling
      aqueous networks designed for controlled complexation and release of small
      molecules.
AB  - Three aqueous self-assembling poly(acrylate) networks have been designed to gain
      insight into the factors controlling the complexation and release of small
      molecules within them. These networks are formed between 8.8% 6A-(2
      aminoethyl)amino-6A-deoxy-6A-beta-cyclodextrin, beta-CDen, randomly substituted
      poly(acrylate), PAAbeta-CDen, and one of the 3.3% 1-(2-aminoethyl)amidoadamantyl,
      ADen, 3.0% 1-(6-aminohexyl)amidoadamantyl, ADhn, or 2.9% 1-(12
      aminododecyl)amidoadamantyl, ADddn, randomly substituted poly(acrylate)s,
      PAAADen, PAAADhn and PAAADddn, respectively, such that the ratio of beta-CDen to
      adamantyl substituents is ca. 3:1. The variation of the characteristics of the
      complexation of the dyes methyl red, methyl orange and ethyl orange in these
      three networks and by beta-cyclodextrin, beta-CD, and PAAbeta-CDen alone provides
      insight into the factors affecting dye complexation. The rates of release of the
      dyes through a dialysis membrane from the three aqueous networks show a high
      dependence on host-guest complexation between the beta-CDen substituents and the
      dyes as well as the structure and the viscosity of the network as shown by ITC,
      1H NMR and UV-vis spectroscopy, and rheological studies. Such networks
      potentially form a basis for the design of controlled drug release systems.

PMID- 29062408
TI  - Influence of the milling parameters on the nucleophilic substitution reaction of
      activated beta-cyclodextrins.
AB  - The present work focuses on the mechanochemical preparation of industrially
      important beta-cyclodextrin (CD) derivatives. Activated CDs have been reacted
      with nitrogen and sulfur nucleophiles using a planetary mill equipped with
      stainless steel, zirconia and glass milling tools of different sizes. It is shown
      that the milling frequency and the number as well as the size of the milling
      balls have an effect on the nucleophilic reaction.

PMID- 29062409
TI  - A novel application of 2-silylated 1,3-dithiolanes for the synthesis of
      aryl/hetaryl-substituted ethenes and dibenzofulvenes.
AB  - Trimethylsilyldiazomethane (TMS-CHN2) reacts readily with hetaryl thioketones to
      give sterically crowded 2-trimethylsilyl-4,4,5,5-tetrahetaryl-1,3-dithiolanes
      with complete regioselectivity at -75  degrees C as well as at rt.
      Thiofluorenone, a relatively stable and highly reactive aryl thioketone, yields
      upon treatment with TMS-CHN2 at -60  degrees C the corresponding 1,3,4
      thiadiazoline. This unstable cycloadduct undergoes decomposition at ca. -45 
      degrees C and the silylated thiocarbonyl S-methanide generated thereby is trapped
      with complete regioselectivity by aryl or hetaryl thioketones forming also
      sterically crowded 2-trimethylsilyl-1,3-dithiolanes. The obtained 1,3
      dithiolanes, by treatment with an equimolar amount of TBAF in a one-pot
      procedure, are converted in high yields into hetaryl/aryl-substituted ethenes or
      dibenzofulvenes, respectively, via a cycloreversion reaction of the intermediate
      1,3-dithiolane carbanion. The presented protocol offers a new, highly efficient
      approach to tetrasubstituted ethenes and dibenzofulvenes bearing aryl and/or
      hetaryl substituents.

PMID- 29062411
TI  - Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of
      tertiary sulfonamides.
AB  - A new and efficient approach to five- and six-membered benzannelated sultams by
      intramolecular C-arylation of tertiary 1-(methoxycarbonyl)methanesulfonamides
      under palladium catalysis is described. In case of the alpha-toluenesulfonamide
      derivative, an unexpected formation of a 2,3-diarylindole was observed under the
      same conditions.

PMID- 29062412
TI  - p-tert-Butylthiacalix[4]arenes functionalized by N-(4'-nitrophenyl)acetamide and
      N,N-diethylacetamide fragments: synthesis and binding of anionic guests.
AB  - New p-tert-butylthiacalix[4]arenes, which are mono-, 1,2-di- and tetrasubstituted
      at the lower rim containing N-(4'-nitrophenyl)acetamide and N,N-diethylacetamide
      groups in cone and partial cone conformations have been synthesized. Their
      complexation ability towards a number of tetrabutylammonium salts n-Bu4NX (X = F
      , Cl-, Br-, I-, CH3CO2-, H2PO4-, NO3-) was studied by UV spectroscopy. The
      effective receptor for the anions studied as well as selective receptors for F-,
      CH3CO2- and H2PO4- ions, which based on the synthesized thiacalix[4]arenes, have
      been obtained. It was shown that p-tert-butylthiacalix[4]arene tetrasubstituted
      at the lower rim by N-(4'-nitrophenyl)acetamide moieties bonded to the anions
      studied with association constants within the range of 3.55 * 103-7.94 * 105 M-1.
      Besides, the binding selectivity for F-, Cl-, CH3CO2-, and H2PO4- anions against
      other anions was in the range of 4.1-223.9. Substituting one or two fragments in
      the macrocycle with N,N-diethylacetamide groups significantly reduces the
      complexation ability of the receptor. In contrast to the 1,3-disubstituted
      macrocycle containing two N-(4'-nitrophenyl)acetamide moieties, the 1,2
      disubstituted thiacalix[4]arene, which contains only one such fragment and a N,N
      diethylacetamide moiety, selectively binds F- anions.

PMID- 29062413
TI  - One-pot multistep mechanochemical synthesis of fluorinated pyrazolones.
AB  - Solventless mechanochemical synthesis represents a technique with improved
      sustainability metrics compared to solvent-based processes. Herein, we describe a
      methodical process to run one solventless reaction directly into another through
      multistep mechanochemistry, effectively amplifying the solvent savings. The
      approach has to consider the solid form of the materials and compatibility of any
      auxiliary used. This has culminated in the development of a two-step, one-jar
      protocol for heterocycle formation and subsequent fluorination that has been
      successfully applied across a range of substrates, resulting in 12 difluorinated
      pyrazolones in moderate to excellent yields.

PMID- 29062410
TI  - Mechanochemical synthesis of small organic molecules.
AB  - With the growing interest in renewable energy and global warming, it is important
      to minimize the usage of hazardous chemicals in both academic and industrial
      research, elimination of waste, and possibly recycle them to obtain better
      results in greener fashion. The studies under the area of mechanochemistry which
      cover the grinding chemistry to ball milling, sonication, etc. are certainly of
      interest to the researchers working on the development of green methodologies. In
      this review, a collection of examples on recent developments in organic bond
      formation reactions like carbon-carbon (C-C), carbon-nitrogen (C-N), carbon
      oxygen (C-O), carbon-halogen (C-X), etc. is documented. Mechanochemical syntheses
      of heterocyclic rings, multicomponent reactions and organometallic molecules
      including their catalytic applications are also highlighted.

PMID- 29062414
TI  - High-speed vibration-milling-promoted synthesis of symmetrical frameworks
      containing two or three pyrrole units.
AB  - The pseudo-five-component reaction between beta-dicarbonyl compounds (2
      molecules), diamines and alpha-iodoketones (2 molecules), prepared in situ from
      aryl ketones, was performed efficiently under mechanochemical conditions
      involving high-speed vibration milling with a single zirconium oxide ball. This
      reaction afforded symmetrical frameworks containing two pyrrole or fused pyrrole
      units joined by a spacer, which are of interest in the exploration of chemical
      space for drug discovery purposes. The method was also extended to the synthesis
      of one compound containing three identical pyrrole fragments via a pseudo-seven
      component reaction. Access to compounds having a double bond in their spacer
      chain was achieved by a different approach involving the homodimerization of 1
      allyl- or 1-homoallylpyrroles by application of cross-metathesis chemistry.

PMID- 29062415
TI  - Solid-state mechanochemical omega-functionalization of poly(ethylene glycol).
AB  - Poly(ethylene glycol) (PEG) is a linear polymer with a wide range of applications
      in chemical manufacturing, drug development and nanotechnology. PEG derivatives
      are being increasingly used to covalently modify small molecule and peptide
      drugs, as well as bioactive nanomaterials in order to improve solubility in
      biological serum, reduce immunogenicity, and enhance pharmacokinetic profiles.
      Herein we present the development of mechanochemical procedures for PEG
      functionalization without the need for bulk solvents, offering a cleaner and more
      sustainable alternative to existing solution-based PEG procedures. The herein
      presented mechanochemical procedures enable rapid and solvent-free derivatization
      of PEG with tosyl, bromide, thiol, carboxylic acid or amine functionalities in
      good to quantitative yields and with no polymer chain oligomerization, proving
      the versatility of the method.

PMID- 29062416
TI  - Are boat transition states likely to occur in Cope rearrangements? A DFT study of
      the biogenesis of germacranes.
AB  - It has been proposed that elemanes are biogenetically formed from germacranes by
      Cope sigmatropic rearrangements. Normally, this reaction proceeds through a
      transition state with a chair conformation. However, the transformation of
      schkuhriolide (germacrane) into elemanschkuhriolide (elemane) may occur through a
      boat transition state due to the final configuration of the elemanschkuhriolide,
      but this transition state is questionable due to its high energy. The possible
      mechanisms of this transformation were studied in the density functional theory
      frame. The mechanistic differences between the transformation of (Z,E)
      germacranes and (E,E)-germacranes were also studied. We found that (Z,E)
      germacranolides are significantly more stable than (E,E)-germacranolides and
      elemanolides. In the specific case of schkuhriolide, even when the boat
      transition state is not energetically favored, a previous hemiacetalization
      lowers enough the energetic barrier to allow the formation of a very stable
      elemanolide that is even more stable than its (Z,E)-germacrane.

PMID- 29062417
TI  - Solvent-free and room temperature synthesis of 3-arylquinolines from different
      anilines and styrene oxide in the presence of Al2O3/MeSO3H.
AB  - A highly efficient, simple and environmentally friendly synthesis of 3
      arylquinolines has been developed in the presence of Al2O3/MeSO3H via one-pot
      reaction of anilines and styrene oxide. This methodology provides very rapid
      access to 3-arylquinolines in good to excellent yields under solvent-free
      conditions at room temperature in air.

PMID- 29062418
TI  - New bio-nanocomposites based on iron oxides and polysaccharides applied to
      oxidation and alkylation reactions.
AB  - Polysaccharides from natural sources and iron precursors were applied to develop
      new bio-nanocomposites by mechanochemical milling processes. The proposed
      methodology was demonstrated to be advantageous in comparison with other
      protocols for the synthesis of iron oxide based nanostructures. Additionally,
      mechanochemistry has enormous potential from an environmental point-of-view since
      it is able to reduce solvent issues in chemical syntheses. The catalytic activity
      of the obtained nanocatalysts was investigated in both the oxidation of benzyl
      alcohol to benzaldehyde and in the alkylation of toluene with benzyl chloride.
      The microwave-assisted oxidation of benzyl alcohol reached 45% conversion after
      10 min. The conversion of the alkylation of toluene in both microwave-assisted
      and conventional heating methods was higher than 99% after 3 min and 30 min,
      respectively. The transformation of benzyl alcohol and toluene into valuable
      product in both the oxidation and alkylation reaction reveals a potential method
      for the valorization of lignocellulosic biomass.

PMID- 29062419
TI  - 1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using
      thioglycosides.
AB  - 1,3-Dibromo-5,5-dimethylhydantoin (DBDMH), an inexpensive, non-toxic and stable
      reagent, is a competent activator of thioglycosides for glycosidic bond
      formation. Excellent yields were obtained when triflic acid (TfOH) or
      trimethylsilyl trifluoromethanesulfonate (TMSOTf) were employed as co-promoters
      in solution or automated glycan assembly on solid phase.

PMID- 29062421
TI  - Mechanochemical Knoevenagel condensation investigated in situ.
AB  - The mechanochemical Knoevenagel condensation of malononitrile with p
      nitrobenzaldehyde was studied in situ using a tandem approach. X-ray diffraction
      and Raman spectroscopy were combined to yield time-resolved information on the
      milling process. Under solvent-free conditions, the reaction leads to a
      quantitative conversion to p-nitrobenzylidenemalononitrile within 50 minutes. The
      in situ data indicate that the process is fast and proceeds under a direct
      conversion. After stopping the milling process, the reaction continues until
      complete conversion. The continuous and the stopped milling process both result
      in crystalline products suitable for single crystal X-ray diffraction.

PMID- 29062422
TI  - Spatial effects in polymer chemistry.

PMID- 29062420
TI  - Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn
      glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety:
      Evidence from conformation analysis by 1H NMR spectroscopy.
AB  - Cell-membrane glycerolipids exhibit a common structural backbone of asymmetric
      1,2-diacyl-sn-glycerol bearing polar head groups in the sn-3 position. In this
      study, the possible effects of sn-3 head groups on the helical conformational
      property around the 1,2-diacyl moiety in the solution state were examined. 1H NMR
      Karplus relation studies were carried out using a series of 1,2-dipalmitoyl-sn
      glycerols bearing different sn-3 substituents (namely palmitoyl, benzyl,
      hydrogen, and phosphates). The 1H NMR analysis indicated that the helical
      property around the 1,2-diacyl moiety is considerably affected by these sn-3
      substituents. The sn-3 hydroxy group induced a unique helical property, which was
      considerably dependent on the solvents used. In CDCl3 solution, three staggered
      conformers, namely gt(+), gg(-) and tg, were randomized, while in more polar
      solvents, the gt(+) conformer with (+)-helicity was amplified at the expense of
      gg(-) and tg conformers. The sn-3 phosphocholine in phosphatidylcholine exhibited
      a greater effect on the gt(+) conformer, which was independent of the solvents
      used. From the 1H NMR analysis, the helical conformational properties around the
      1,2-diacyl moiety conformed to a simple empirical rule, which permitted the
      proposal of a conformational diagram for 1,2-dipalmitoyl-sn-glycerols in the
      solution states.

PMID- 29062423
TI  - Transition-metal-free synthesis of 3-sulfenylated chromones via KIO3-catalyzed
      radical C(sp2)-H sulfenylation.
AB  - The reactions between o-hydroxylphenyl-functionalized enaminones and sulfonyl
      hydrazines providing 3-sulfenylated chromones via domino chromone ring
      construction and C(sp2)-H bond sulfenylation have been achieved under transition
      metal-free conditions by using KIO3 as the only catalyst.

PMID- 29062424
TI  - Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at
      room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes.
AB  - We developed a direct vicinal difunctionalization of alkenes with iodine and TBHP
      at room temperature. This iodination and peroxidation in a one-pot synthesis
      produces 1-(tert-butylperoxy)-2-iodoethanes, which are inaccessible through
      conventional synthetic methods. This method generates multiple radical
      intermediates in situ and has excellent regioselectivity, a broad substrate scope
      and mild conditions. The iodine and peroxide groups of 1-(tert-butylperoxy)-2
      iodoethanes have several potential applications and allow further chemical
      modifications, enabling the preparation of synthetically valuable molecules.

PMID- 29062425
TI  - Intramolecular glycosylation.
AB  - Carbohydrate oligomers remain challenging targets for chemists due to the
      requirement for elaborate protecting and leaving group manipulations,
      functionalization, tedious purification, and sophisticated characterization.
      Achieving high stereocontrol in glycosylation reactions is arguably the major
      hurdle that chemists experience. This review article overviews methods for
      intramolecular glycosylation reactions wherein the facial stereoselectivity is
      achieved by tethering of the glycosyl donor and acceptor counterparts.

PMID- 29062426
TI  - Mechanically induced oxidation of alcohols to aldehydes and ketones in ambient
      air: Revisiting TEMPO-assisted oxidations.
AB  - The present work addresses the development of an eco-friendly and cost-efficient
      protocol for the oxidation of primary and secondary alcohols to the corresponding
      aldehydes and ketones by mechanical processing under air. Ball milling was shown
      to promote the quantitative conversion of a broad set of alcohols into carbonyl
      compounds with no trace of an over-oxidation to carboxylic acids. The
      mechanochemical reaction exhibited higher yields and rates than the classical,
      homogeneous, TEMPO-based oxidation.

PMID- 29062427
TI  - Complexation of molecular clips containing fragments of diphenylglycoluril and
      benzocrown ethers with paraquat and its derivatives.
AB  - The complexation of molecular clips containing fragments of diphenylglycoluril
      and benzocrown ethers with paraquat and its derivatives has been studied both in
      solution and in the solid state. In this paper we studied the influence of the
      crown ether ring size and the nature of the substituents at the nitrogen atoms of
      the paraquat derivatives on the composition and stability of these complexes.

PMID- 29062428
TI  - Main group mechanochemistry.
AB  - Over the past decade, mechanochemistry has emerged as a powerful methodology in
      the search for sustainable alternatives to conventional solvent-based synthetic
      routes. Mechanochemistry has already been successfully applied to the synthesis
      of active pharmaceutical ingredients (APIs), organic compounds, metal oxides,
      coordination compounds and organometallic complexes. In the main group arena,
      examples of synthetic mechanochemical methodologies, whilst still relatively
      sporadic, are on the rise. This short review provides an overview of recent
      advances and achievements in this area that further validate mechanochemistry as
      a credible alternative to solution-based methods for the synthesis of main group
      compounds and frameworks.

PMID- 29062429
TI  - Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of
      bicyclic nucleosides.
AB  - Conversion of D-glucose to 4-C-hydroxymethyl-1,2-O-isopropylidene-alpha-D
      ribofuranose, which is a key precursor for the synthesis of different types of
      bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of
      the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-alpha-D
      xylofuranose. A convenient environment friendly Novozyme(r)-435 catalyzed
      selective acetylation methodology has been developed for the separation of an
      epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields.
      The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C
      hydroxymethyl-1,2-O-isopropylidene-alpha-D-ribo- and xylofuranose obtained by
      enzymatic acetylation, has been confirmed by an X-ray study on their
      corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two
      separated epimers were used for the convergent synthesis of two different types
      of bicyclic nucleosides, which confirms their synthetic utility.

PMID- 29062431
TI  - Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated
      side chains.
AB  - Using an aerobic oxidative coupling, different new imidazo[1,2-a]-N-heterocycles
      with gem-difluroroalkyl side chains have been prepared in fair yields by the
      reaction of gem-difluoroenones with aminopyridines, -pyrimidines and 
      pyridazines. Condensed heterocycles of this type play an important role as key
      core structures of various bioactive compounds. Further, starting with a
      chloroimidazopyridazine derivative, Pd-catalyzed coupling reactions as well as
      nucleophilic substitutions have been performed successfully in order to increase
      the molecular diversity.

PMID- 29062430
TI  - Preactivation-based chemoselective glycosylations: A powerful strategy for
      oligosaccharide assembly.
AB  - Most glycosylation reactions are performed by mixing the glycosyl donor and
      acceptor together followed by the addition of a promoter. While many
      oligosaccharides have been synthesized successfully using this premixed strategy,
      extensive protective group manipulation and aglycon adjustment often need to be
      performed on oligosaccharide intermediates, which lower the overall synthetic
      efficiency. Preactivation-based glycosylation refers to strategies where the
      glycosyl donor is activated by a promoter in the absence of an acceptor. The
      subsequent acceptor addition then leads to the formation of the glycoside
      product. As donor activation and glycosylation are carried out in two distinct
      steps, unique chemoselectivities can be obtained. Successful glycosylation can be
      performed independent of anomeric reactivities of the building blocks. In
      addition, one-pot protocols have been developed that have enabled multiple-step
      glycosylations in the same reaction flask without the need for intermediate
      purification. Complex glycans containing both 1,2-cis and 1,2-trans linkages,
      branched oligosaccharides, uronic acids, sialic acids, modifications such as
      sulfate esters and deoxy glycosides have been successfully synthesized. The
      preactivation-based chemoselective glycosylation is a powerful strategy for
      oligosaccharide assembly complementing the more traditional premixed method.

PMID- 29062432
TI  - Synthesis of substituted Z-styrenes by Hiyama-type coupling of
      oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane.
AB  - Several Hiyama cross-coupling reactions of oxasilacycloalkenes and aryl iodides
      are described that produce trisubstituted Z-styrenes in moderate to excellent
      yields. Both electron-rich and electron-poor aryl iodides are tolerated in the
      cross-coupling reaction. The oxasilacycloalkene coupling partners were prepared
      by ruthenium-catalyzed intramolecular anti-hydrosilylation of alkynols. One of
      the cross-coupling products was converted to a 1-benzoxocane, albeit in low
      yield, using an intramolecular Buchwald-Hartwig etherification. The cyclic ether
      produced contains the carbon skeleton of heliannuol A.

PMID- 29062433
TI  - Correction: Mechanochemical enzymatic resolution of N-benzylated-beta3-amino
      esters.
AB  - [This corrects the article DOI: 10.3762/bjoc.13.167.].

PMID- 29062434
TI  - Novel approach to hydroxy-group-containing porous organic polymers from bisphenol
      A.
AB  - We successfully employed bisphenol A and several different formyl-containing
      monomers as useful building blocks to construct a series of hydroxy-group
      containing porous organic polymers in a sealed tube at high temperature. Fourier
      transform infrared and solid-state 13C CP/MAS NMR spectroscopy are utilized to
      characterize the possible structure of the obtained polymers. The highest
      Brunauer-Emmet-Teller specific surface area of the phenolic-resin porous organic
      polymers (PPOPs) is estimated to be 920 m2 g-1. The PPOPs exhibit a highest
      carbon dioxide uptake (up to 15.0 wt % (273 K) and 8.8 wt % (298 K) at 1.0 bar),
      and possess moderate hydrogen storage capacities ranging from 1.28 to 1.04 wt %
      (77 K) at 1.0 bar. Moreover, the highest uptake of methane for the PPOPs is
      measured as 4.3 wt % (273 K) at 1.0 bar.

PMID- 29062435
TI  - Solid-state studies and antioxidant properties of the gamma-cyclodextrin.fisetin
      inclusion compound.
AB  - Fisetin is a natural antioxidant with a wide range of nutraceutical properties,
      including antidiabetic, neuroprotecting, and suppression or prevention of tumors.
      The present work describes the preparation of a water-soluble, solid inclusion
      compound of fisetin with gamma-cyclodextrin (gamma-CD), a cyclic oligosaccharide
      approved for human consumption. A detailed physicochemical analysis of the
      product is carried out using elemental analysis, powder X-ray diffraction (PXRD),
      Raman, infrared and 13C{1H} CP-MAS NMR spectroscopies, and thermal analysis (TGA)
      to verify fisetin inclusion and to present a hypothetical structural arrangement
      for the host-guest units. The antioxidant activity of the gamma-CD.fisetin
      inclusion compound is evaluated by the DPPH assay.

PMID- 29062436
TI  - Summary of a Cochrane review: Wendan decoction traditional Chinese medicine for
      schizophrenia.

PMID- 29062437
TI  - Daytime Effect of Monochromatic Blue Light on EEG Activity Depends on Duration
      and Timing of Exposure in Young Men.
AB  - Growing evidence suggests an alerting effect of monochromatic blue light on brain
      activity. Little is known about the moderation of those effects by timing and
      duration of exposure. The present electroencephalography (EEG ) study examined
      such moderations on delta, theta, alpha1, alpha2, and beta EEG bands. A
      counterbalanced repeated-measures design was applied. The 16-hr daytime period
      was divided into three sessions: 07:00-12:20, 12:20-17:40, and 17:40-23:00
      (timing of exposure). Two light conditions comparable in luminance but differing
      in wavelength were applied, namely polychromatic white light and monochromatic
      blue light (460 nm). There were two durations of exposure-the shorter one lasting
      30 min and the longer one lasting 4 hrs. Thirty male students participated in the
      study. Four factors analyses of variance (ANOV As, for light conditions, timing
      of exposure, duration of exposure, and brain area) were performed on each EEG
      band. Results indicated an alerting effect of short exposure to monochromatic
      blue light at midday and in the evening, which was demonstrated by a decrease in
      lower frequency bands (alpha1, delta, and theta, respectively). Long exposure to
      blue light may have a reverse effect, especially in the morning and at midday,
      when increases in lower frequency bands (theta in the morning and theta and
      alpha1 at midday) were observed. It can be concluded that the daytime effect of
      monochromatic blue light on EEG activity depends on timing and duration of
      exposure.

PMID- 29062438
TI  - Examining Developmental Changes in Children's Motor Imagery: A Longitudinal
      Study.
AB  - Using a longitudinal design, the present study examined developmental changes in
      the employment of (motor) imagery strategies on the hand laterality judgment
      (HLJ) task in children. All children (N = 23) participated three times, at ages
      of 5, 6, and 7 years. Error percentages and response durations were compared to a
      priori defined sinusoid models, representing different strategies to judge hand
      laterality. Response durations of correct and incorrect trials were included.
      Observed data showed that task performance was affected by motor constraints,
      both in children who performed accurately at 5 years of age and in the children
      who did not. This is the first study to show that 5-year-olds-even when not
      successful at the task-employ motor imagery when engaged in this task.
      Importantly, although the children became faster and more accurate with age, no
      developmental changes in the employed motor imagery strategy were observed at
      ages of 5, 6, and 7 years. We found that 5-year-old children are able to use a
      motor imagery strategy to perform the HL J task. Although performance on this
      task improved with age, our analyses showed that the employed strategy to solve
      this task remained invariant across age.

PMID- 29062439
TI  - Problems in bariatric patient care - challenges for dieticians.
AB  - Obesity management options include a low-calorie diet, behavioral therapy,
      regular physical activity and pharmacological therapy. However, treatment failure
      is frequently encountered, most of these methods are ineffective, and a positive
      outcome is rarely maintained in the long term. In morbidly obese patients,
      bariatric surgery is considered the most effective treatment for obesity as well
      as the accompanying diseases. Bariatric surgery promotes much greater weight loss
      than conservative treatment, regardless of the applied surgical technique.
      Bariatric surgery patients should receive professional perioperative
      (preoperative, intraoperative and postoperative) care from a multidisciplinary
      team of specialists, including a bariatric surgeon, a general practitioner, a
      dietitian and a health psychologist. Patients require postoperative nutritional
      counseling to be able to stabilize their weight and maintain long-term weight
      loss after surgery. Patients are guided by bariatric dietitians through the
      process of adopting new eating habits and behavior, learning how to make healthy
      food choices.

PMID- 29062440
TI  - The feasibility and safety of thoracoscopic surgery under epidural and/or local
      anesthesia for spontaneous pneumothorax: a meta-analysis.
AB  - The aim of this study was to compare thoracoscopic surgery for spontaneous
      pneumothorax under epidural and/or local anesthesia (ELA) with that under general
      anesthesia and prove the feasibility and safety of thoracoscopic surgery under
      ELA for spontaneous pneumothorax. Relevant studies were searched in five
      databases from their date of publication to June 2016. We collected and analyzed
      the data concerning operative time, hospital stay, complications, air leak,
      recurrence and perioperative mortality. A forest plot was performed to compare
      the differences between the two groups. There were no significant differences
      between the ELA group and the general anesthesia (GA) group in operative time,
      hospital stay, complications, air leak or recurrence. There were 6 deaths
      reported in two studies. However, patients in the ELA group had significantly
      shorter global operating room time. Our study demonstrated that ELA, in
      comparison with GA, is feasible and safe for thoracoscopic surgery of spontaneous
      pneumothorax.

PMID- 29062441
TI  - Is minimally invasive surgical treatment justified for severe acute necrotizing
      pancreatitis patients with dysfunction of two or more organ systems?
AB  - INTRODUCTION: When minimally invasive therapy was introduced, it became possible
      to cure some patients without open surgery, or at least delay the operation for
      longer than a month. AIM: To determine the optimal timing to operate on patients
      with severe acute necrotizing pancreatitis based on the severity of organ
      insufficiency. MATERIAL AND METHODS: A retrospective analysis was performed in
      all severe acute necrotizing pancreatitis patients treated in Vilnius University
      Hospital Santaros Klinikos (VUL SK) from 2007 to 2016. The patients were divided
      into groups based on the number of dysfunctional organ systems (one or more) and
      whether the minimally invasive step-up approach to treatment was used. RESULTS:
      The patients with one organ dysfunction had a delay of 35 (without the step-up
      approach) and 36 (with the step-up approach) days before the open surgery, while
      the patients with two or more organ systems' dysfunction had almost an identical
      delay of 28 days, using both surgical treatment methods. The mortality of the
      patients who had one organ dysfunction and in whom the step-up approach was used
      was 0%, while in patients without the step-up approach it was 41.7%. In the two
      or more organ systems' dysfunction group, the mortality for those treated with a
      step-up approach was 64.3%, and without it 70.7%. CONCLUSIONS: The surgical
      treatment should be initiated with a minimally invasive procedure. Additionally,
      the surgery on patients with two or more organ systems' dysfunction should not be
      delayed for more than one month.

PMID- 29062442
TI  - Multiple plastic biliary stent placement in the management of large and multiple
      choledochal stones: single center experience and review of the literature.
AB  - INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) with
      sphincterotomy is the first step treatment modality of choledocholithiasis. In
      spite of an extended sphincterotomy, 10-15% of complex choledochal stones (larger
      than 15 mm and/or more than 3 stones) cannot be removed and recurrent ERCP
      procedures may be needed. AIM: To evaluate the role and efficiency of multiple
      biliary stent application in the treatment of large and multiple choledochal
      stones. MATERIAL AND METHODS: Patients with complex choledochal stones and
      patients with inadequate choledochal clearance during ERCP were included in the
      study. The study group was divided into 2 groups as the placement of single (n =
      27 patients) or multiple stents (n = 58 patients). After a mean time interval of
      21 days (10-28), the ERCP procedure was tried for the second time and a stent was
      placed in case of recurrence. RESULTS: Successful biliary drainage was provided
      in both groups. The decrease in the longitudinal or transverse size of the stones
      after stent placement was found to be statistically significant in both groups (p
      = 0.001). Cholestatic enzymes (alkaline phosphatase (ALP), gamma
      glutamyltransferase (GGT)) and bilirubin levels decreased significantly in both
      groups following stenting (p = 0.001). Additionally, multiple stents functioned
      as a bridge starting from the first ERCP to full clearance in patients with large
      and multiple stones which could not be removed at once and saved them from the
      possible morbidities of an invasive operation. CONCLUSIONS: Endoscopic multiple
      biliary stent placement should be preferred in the treatment of patients with
      complex choledochal stones and high rates of co-morbidity, as a safe alternative
      to surgery.

PMID- 29062443
TI  - The choice of optimal antireflux procedure after laparoscopic cardiomyotomy: two
      decades of clinical experience in one center.
AB  - INTRODUCTION: Two types of partial wrap are commonly performed in achalasia
      patients after Heller myotomy: the posterior 270 degrees  fundoplication (Toupet)
      and the anterior 180 degrees  fundoplication (Dor). The optimal type of
      fundoplication (posterior vs. anterior) is still debated. AIM: To compare the
      long-term rates of dysphagia, reflux symptoms and patient satisfaction with
      current postoperative condition between two fundoplication groups in achalasia
      treatment. MATERIAL AND METHODS: Our retrospective study included 97 consecutive
      patients with achalasia: 37 patients underwent laparoscopic posterior Toupet (270
      degrees ) fundoplication followed by Heller myotomy (group I); 60 patients
      underwent laparoscopic anterior partial Dor fundoplication followed by Heller
      myotomy (group II). Long-term follow-up results included evaluation of dysphagia
      symptoms, intensity of heartburn and patient satisfaction with current condition.
      RESULTS: Patients in these two groups did not differ according to age, weight,
      height, postoperative stay or follow-up period. Laparoscopic myotomy with
      posterior Toupet fundoplication was effective in 89% of patients, while
      laparoscopic myotomy with anterior Dor was effective in 93% of patients (p >
      0.05). 11% of patients after posterior Toupet fundoplication had clinically
      significant heartburn vs. 35% of patients after anterior Dor fundoplication (p <
      0.05). Overall patient satisfaction with current condition was 88%, with no
      significant difference between the groups. CONCLUSIONS: According to our study
      results, the two laparoscopic techniques were similarly effective in reducing
      achalasia symptoms, but postoperative clinical manifestation of heartburn is
      significantly more frequent after anterior Dor fundoplication (35% vs. 11%). The
      majority of patients (88%) were satisfied with operation outcomes.

PMID- 29062444
TI  - Laparoscopic repair of large suprapubic hernias.
AB  - INTRODUCTION: Suprapubic hernia is the term to describe ventral hernias located
      less than 4 cm above the pubic arch in the midline. Hernias with an upper margin
      above the arcuate line encounter technical difficulties, and the differences in
      repair methods forced us to define them as large suprapubic hernias. AIM: To
      present our experience with laparoscopic repair of large suprapubic hernias that
      allows adequate mesh overlap. MATERIAL AND METHODS: Nineteen patients with
      suprapubic incisional hernias who underwent laparoscopic repair between May 2013
      and January 2015 were included in the study. Patients with laparoscopic
      extraperitoneal repair who had a suprapubic hernia with an upper margin below the
      arcuate line were excluded. RESULTS: Two men and 17 women, with a mean age of
      58.2, underwent laparoscopic repair. Most of the incisions were midline vertical
      (13/68.4%). Twelve (63.1%) of the patients had previous incisional hernia repair
      (PIHR group); the mean number of previous incisional hernia repair was 1.4. Mean
      defect size of the PIHR group was higher than in patients without previous repair
      - 107.3 cm2 vs. 50.9 cm2 (p < 0.05). Mean operating time of the PIHR group was
      higher than in patients without repair - 126 min vs. 77.9 min (p < 0.05).
      Although all complications occurred in the PIHR group, there was no statistically
      significant difference. CONCLUSIONS: Laparoscopic repair of large suprapubic
      hernias can be considered as the first option in treatment. The low recurrence
      rates reported in the literature and the lack of recurrence, as observed in our
      study, support this view.

PMID- 29062445
TI  - The impact of three-dimensional reconstruction on laparoscopic-assisted surgery
      for right-sided colon cancer.
AB  - INTRODUCTION: During laparoscopic-assisted colorectal surgery (LACS) for right
      sided colon cancer patients, we performed three-dimensional (3D) surgical
      simulation to investigate vascular anatomy, including the ileocolic artery (ICA),
      right colic artery (RCA) and superior mesenteric vein (SMV). AIM: We also used 3D
      imaging to examine the shortest distance from the root of the ileocolic vein
      (ICV) to the gastrocolic trunk (GCT). MATERIAL AND METHODS: We analyzed 46 right
      sided colon cancer patients who underwent 3D-simulated LACS. We also examined a
      control group of 20 right-sided colon cancer patients who underwent LACS without
      3D imaging. Patients who received such assessments were classified into the
      following two groups based on the vessel arrangement patterns of the ICA and SMV:
      the type A group, in which the ICA crosses anterior to the SMV, and the type B
      group, in which the ICA crosses posterior to the SMV. The shortest length from
      the root of the ICV to the GCT (D mm) was measured via 3D imaging. Patient
      characteristics and perioperative outcomes for these three groups were compared.
      RESULTS: The mean D mm for all cases was 29.2 +/-5.21 mm. Mean D mm values for
      the type A and type B groups were 27.8 +/-4.21 and 30.5 +/-5.53 mm, respectively.
      Intraoperative blood loss was lower in the type A group (41.8 +/-27.5 g) and the
      type B group (44.5 +/-31.6 g) than that in the control group (86.8 +/-27.5 g) (p
      = 0.013). CONCLUSIONS: 3D imaging was useful for understanding anatomical
      relationships during LACS.

PMID- 29062446
TI  - The effect of zero-ischaemia laparoscopic minimally invasive partial nephrectomy
      using the modified sequential preplaced suture renorrhaphy technique on long-term
      renal functions.
AB  - INTRODUCTION: Laparoscopic minimally invasive partial nephrectomy (MIPN) is the
      preferred technique in renal surgery, especially T1 phase kidney tumours, and it
      is recommended for the protection of renal functions in methods that do not
      involve ischaemia. AIM: To evaluate long-term renal functions of zero-ischaemia
      laparoscopic MIPN patients who underwent a modified sequential preplaced suture
      renorrhaphy technique. MATERIAL AND METHODS: In a total of 17 renal units in 16
      patients with kidney tumours that were determined incidentally and did not cause
      any complaints, the masses were extracted via laparoscopic partial nephrectomy
      (LPN) using the modified sequential preplaced suture renorrhaphy technique.
      Creatinine and estimated glomerular filtration rate (eGFR) values of the patients
      were measured preoperatively and on the first day and after 12 months
      postoperatively, and the results were compared. RESULTS: The differences between
      the pre- and postoperative values were statistically significant (p = 0.033, p =
      0.045), but the changes in postoperative creatinine and eGFR values were
      clinically insignificant. While the differences between preoperative and first
      day postoperative creatinine and eGFR values were found to be statistically
      significant (p = 0.039, p = 0.042, respectively), a statistically significant
      difference was not detected between preoperative and 12-month postoperative
      creatinine and eGFR values (p = 0.09, p = 0.065, respectively). The global
      percentage of functional recovery was measured as 92.5% on the first day and
      95.9% at the 12th month. CONCLUSIONS: The modified sequential preplaced suture
      renorrhaphy technique is an effective, reliable method for avoiding complications
      and preserving renal functions and nephrons in appropriate patients.

PMID- 29062447
TI  - Overcoming the learning curve of single-port total laparoscopic hysterectomy with
      barbed suture: a single surgeon's initial experience.
AB  - INTRODUCTION: Single-port total laparoscopic hysterectomy (TLH) has not been
      widely used because of its technical difficulty and steep learning curve,
      especially the laparoscopic suturing of the vaginal stump. Barbed suturing is a
      new technology that has the potential to greatly facilitate laparoscopic
      suturing. AIM: To compare surgical outcomes and vaginal vault healing between
      barbed sutures and traditional sutures in the repair of the vaginal vault during
      single-port TLH. MATERIAL AND METHODS: Between August 2013 and June 2015, we
      performed single-port TLH in 85 consecutive patients for benign or premalignant
      gynecological conditions. The first 48 patients underwent single-port TLH with
      traditional interrupted sutures, and the next 37 patients underwent single-port
      TLH with absorbable unidirectional knotless barbed sutures for repair of the
      vaginal vault. RESULTS: The patient characteristics (age, body mass index),
      procedures performed, uterine weight, and uterine disease were similar between
      the groups. There were no differences in blood loss, hemoglobin change, length of
      hospital stay, or perioperative complications. Operative time and the time
      required for vaginal cuff suturing were significantly shorter in the barbed
      suture group than in the traditional suture group (57.8 +/-13.5 vs. 80.1 +/-18.7
      min, p < 0.001; 5.5 +/-1.7 vs. 12.9 +/-3.5 min, p < 0.001). Moreover, the use of
      barbed sutures significantly reduced the incidence of vaginal granulation tissue
      formation (2.7% vs. 35.4%, p < 0.001). CONCLUSIONS: Use of barbed sutures in
      single-port TLH reduced the operative time, suturing time of the vaginal vault,
      and formation of vaginal granulation tissue. Barbed suturing may help overcome
      surgical difficulties and vaginal cuff complications.

PMID- 29062449
TI  - Injection laryngoplasty as miniinvasive office-based surgery in patients with
      unilateral vocal fold paralysis - voice quality outcomes.
AB  - INTRODUCTION: Injection laryngoplasty (glottis augmentation) is the preferred
      method in surgical management of unilateral vocal fold paralysis (UVFP).
      Traditionally, these procedures are performed in the operating room. Nowadays,
      however, these procedures have moved into the office. AIM: To evaluate the voice
      quality after transoral injection laryngoplasty under local anaesthesia in
      patients with unilateral vocal fold paralysis. MATERIAL AND METHODS: Fourteen
      subjects (5 women and 9 men) with unilateral vocal fold paresis (9 with right
      vocal fold paresis and 5 with left vocal fold paresis) were included in the
      study. The mean age of the group was 57.8 +/-19.0 years (32-83 years). All of the
      injection laryngoplasties were performed transorally, under local anaesthesia.
      The injection material was calcium hydroxylapatite. Before and 1, 3 and 6 months
      after the procedure the following variables were evaluated: voice perception,
      videostroboscopy, acoustic analysis, aerodynamic evaluation, and the subjective
      rating of the voice quality by the patient. RESULTS: After injection
      laryngoplasty, complete glottal closure was achieved or there was a significant
      improvement in the glottal closure of each subject. We noted great improvement in
      the post-injection objective and subjective voice outcomes and patients reported
      improvement in the voice-related quality of life. CONCLUSIONS: The transoral
      approach for injection laryngoplasty under local anaesthesia is an effective and
      safe way to treat incomplete glottal closure in patients with UVFP. The transoral
      approach is an efficient alternative to other surgical techniques used for vocal
      fold injection.

PMID- 29062448
TI  - Arm reduced robotic-assisted laparoscopic hysterectomy with transvaginal cuff
      closure.
AB  - INTRODUCTION: The use of robotics for benign etiology in gynecology has not
      proven to be more beneficial when compared to traditional laparoscopy. The major
      concern regarding robotic hysterectomy stems from its high cost. AIM: To evaluate
      the clinical utility and effectiveness of one-arm reduced robotic-assisted
      laparoscopic hysterectomy as a cost-effective surgical option for total robotic
      hysterectomy. MATERIAL AND METHODS: A sample population of 54 women who underwent
      robotic-assisted laparoscopic surgery for benign gynecologic indications was
      evaluated, and two groups were identified: (1) the two-armed robotic-assisted
      laparoscopic surgery group (n = 38 patients), and (2) the three-armed robotic
      assisted laparoscopic surgery group (n = 16 patients). RESULTS: An increased cost
      was observed when three-armed robotic surgery was employed for benign gynecologic
      surgery (p < 0.001). The cost reduction observed in the study group was primarily
      derived from one robotic arm reduction and vaginal closure of the cuff. This cost
      reduction was achieved without an increase in complication rates or undesirable
      postoperative outcomes. An estimated profit between $399.5 and $421.5 was made
      for each patient depending on the suture material chosen for cuff closure. Two
      armed surgery resulted in an 18.6% reduction in procedure-specific costs for
      robotic hysterectomy. CONCLUSIONS: Two-armed robotic-assisted laparoscopic
      hysterectomy appears to be a cost-effective solution for robotic gynecologic
      surgery. This surgical solution can be performed as effectively as classical
      three-armed robotic hysterectomies for benign indications without the risk of
      increased surgical-related morbidities. This approach has the potential to be a
      widely preferred surgical approach in medical communities where cost reduction is
      one of the primary determinants of surgery type.

PMID- 29062450
TI  - Perioperative outcomes in minimally invasive direct coronary artery bypass versus
      off-pump coronary artery bypass with sternotomy.
AB  - INTRODUCTION: Surgical treatment of isolated left anterior descending coronary
      artery disease can be performed with either minimally invasive direct coronary
      artery bypass via a left anterior thoracotomy (MIDCAB) or off-pump coronary
      artery bypass via a median sternotomy (OPCAB). AIM: To compare the perioperative
      outcomes of patients undergoing MIDCAB or OPCAB surgery. MATERIAL AND METHODS:
      Patients who underwent either MIDCAB or OPCAB for isolated left anterior
      descending (LAD) coronary artery disease between October 2013 and December 2015
      were retrospectively evaluated. Operations were carried out by the same surgical
      team. Preoperative, intraoperative and postoperative data of the patients were
      recorded for analyses. RESULTS: Twenty-three patients (7 females, 16 males)
      underwent MIDCAB surgery, and 24 patients (4 female, 20 males) underwent OPCAB
      surgery. The two groups were comparable regarding preoperative patient
      characteristics. Duration of mechanical ventilation (5.1 +/-0.7 h vs. 6.6 +/-0.9
      h), intensive care unit stay (19.4 +/-2.5 h vs. 45.8 +/-5.4 h) and hospital stay
      (4.3 +/-0.4 days vs. 5.6 +/-0.8 days) were significantly shorter in the MIDCAB
      group (p < 0.01). Patients in the OPCAB group required significantly more blood
      transfusions (1.83 +/-0.38 units vs. 0.17 +/-0.38 units) and fresh frozen plasma
      use (2.33 +/-0.96 units vs. 0.69 +/-0.76 units) (p < 0.01). Conversion to
      sternotomy was not required in the MIDCAB group. There was no mortality,
      conversion to cardiopulmonary bypass or serious complication in either group.
      CONCLUSIONS: We believe that the MIDCAB technique is more advantageous than the
      OPCAB technique in the treatment of patients with a critical LAD lesion.

PMID- 29062451
TI  - Two cases of laparoscopic total colectomy with natural orifice specimen
      extraction and review of the literature.
AB  - We present two cases of natural orifice specimen extraction (NOSE) after
      laparoscopic total colectomy and ileorectal anastomosis (TC-IRA), and we also
      review all of the previously reported cases. Our aim was to focus on patient
      selection for NOSE after TC-IRA. The PubMed and Google Scholar databases were
      scanned. Demographic features, surgical indications, and techniques were
      analyzed. Basic calculations were used for statistical analysis. A total of 13
      cases were detected in addition to our 2 cases. All of the specimens were removed
      through the natural orifices successfully. No case required a diverting
      ileostomy. No patients were converted to open surgery or to conventional
      laparoscopy. Complications were reported in three patients. Transanal extractions
      were performed in 12 cases (10 colonic inertia, 2 polyposis), and transvaginal
      extractions were performed in 3 cases (2 malignancy, 1 colonic inertia). Both
      transanal and transvaginal specimen extractions after laparoscopic TC-IRA can be
      preferred. However, transanal extraction seems to be feasible in cases of TC for
      benign disease with a limited mesenteric-omental resection. If the indication is
      a malignancy requiring a mesenteric-omental resection, a transvaginal route
      should be preferred for a voluminous specimen.

PMID- 29062452
TI  - Enterocutaneous fistula: a novel video-assisted approach.
AB  - Video-assisted anal fistula treatment (VAAFT) is a novel minimally invasive and
      sphincter-saving technique to treat complex anal fistulas described by Meinero in
      2006. An enterocutaneous fistula is an abnormal communication between the bowel
      and the skin. Most cases are secondary to surgical complications, and managing
      this condition is a true challenge for surgeons. Postoperative fistulas account
      for 75-85% of all enterocutaneous fistulas. The aim of paper was to devise a
      minimally invasive technique to treat enterocutaneous fistulas. We used the same
      principles of VAAFT applied to other conditions, combining endoluminal vision of
      the tract with colonoscopy to identify the internal opening. We present a case of
      a 78-year-old woman who was subjected to a total colectomy for cecum and sigmoid
      synchronous adenocarcinoma. The postoperative course was complicated with an
      enterocutaneous fistula, treated with conservative measures, which recurred
      during follow-up. We performed video-assisted fistula treatment using a
      fistuloscope combined with a colonoscope. Once we identified the fistula tract,
      we performed cleansing and destruction of the tract, applied synthetic
      cyanoacrylate and sealed the internal opening with clips through an endoluminal
      approach. The patient was discharged 5 days later without complications. Two
      months later the wound was completely healed without evidence of recurrence. This
      procedure represents an alternative treatment for enterocutaneous fistula using a
      minimally invasive technique, especially in selected patients not able to undergo
      major surgery.

PMID- 29062453
TI  - Schwannoma in the porta hepatis - laparoscopic excision under laparoscopic
      ultrasound guidance.
AB  - Schwannomas are usually benign tumors attached to peripheral nerves and are
      rarely found in the gastrointestinal tract. Schwannomas in the porta hepatis are
      extremely rare, with only 15 cases described in the literature to date. A 22-year
      old female patient presented with colicky upper abdominal pain lasting 3 months.
      Magnetic resonance imaging of the abdominal cavity revealed a tumor in the porta
      hepatis. The patient was qualified for laparoscopy. The tumor was totally excised
      laparoscopically under guidance of laparoscopic ultrasound without intra- or
      postoperative complications. Postoperative histopathological examination
      confirmed the porta hepatic schwannoma. The patient recovered uneventfully with
      very good cosmetic results. In the follow-up period of 5 months we have not
      observed any abdominal or general health problems. The present case is the first
      report in the world of laparoscopic ultrasound guided laparoscopic excision of a
      porta hepatic schwannoma.

PMID- 29062455
TI  - Laparoscopic pyloroplasty for perforated peptic ulcer.
AB  - Peptic ulcer is a common disease affecting millions of people every year. Despite
      improved understanding and treatment of the disease, the number of patients
      admitted with duodenal peptic ulcer perforation has not decreased. Deaths from
      peptic ulcer disease overcome other common emergency situations. Laparoscopic
      repair of the perforated peptic ulcer (PPU) is the gold standard approach for
      simple perforation. However, in patients with large perforated chronic ulcers
      laparotomy with pyloroplasty is the standard treatment. It is generally accepted
      to perform open surgery in PPU emergencies because of the greater knowledge and
      experience gathered over the past decades and less potential harm for the patient
      or surgical complications. We present a case of successful laparoscopic
      pyloroplasty of a perforated duodenal ulcer with stenosis.

PMID- 29062454
TI  - Laparoscopic total gastrectomy for a giant gastrointestinal stromal tumor (GIST)
      with acute massive gastrointestinal bleeding: a case report.
AB  - Gastrointestinal stromal tumors (GISTs) include 80% of gastrointestinal
      mesenchymal tumors that originate from interstitial Cajal cells and include 0.1
      3% of GI malignancies, and the stomach is the most commonly involved organ. The
      only potentially curative treatment is surgical resection with clear margins.
      Although laparoscopic resection of small GISTs is a standard treatment, there is
      controversy about laparoscopic surgical resection for large and giant GISTs. A 52
      year-old woman, a known case of large GIST of the stomach that was under
      neoadjuvant imatinib therapy, was admitted to the emergency department due to
      acute massive gastrointestinal bleeding (GIB). The patient underwent laparoscopic
      total gastrectomy and received adjuvant imatinib after surgery. Laparoscopic
      resection is a safe and feasible method in large and giant GISTs with oncologic
      and long-term outcomes comparable to open surgery, and with better short-term
      outcomes.

PMID- 29062456
TI  - Effect of an 8K ultra-high-definition television system in a case of laparoscopic
      gynecologic surgery.
AB  - Various endoscopic devices have been developed for advanced minimally invasive
      surgery. We recently applied a new 8K ultra-high-definition television system
      during laparoscopic treatment of endometriosis. The procedure, which is described
      in detail, stands as the first reported application of an 8K ultra-high
      definition system for laparoscopic gynecologic surgery. Comparison is made
      between depiction of the lesion by the new system and depiction by a full high
      definition system. Improved diagnostic accuracy resulted from the increased image
      resolution, and we believe that this and other advantages will lead to widespread
      acceptance and further application of 8K ultra-high-definition systems in the
      field of gynecologic surgery.

PMID- 29062457
TI  - Late type III endoleak after thoracic endovascular aneurysm repair and previous
      infrarenal stent graft implantation - a case report and review of the literature.
AB  - Thoracic endovascular aortic repair (TEVAR) effectively improved the results of
      thoracic aortic aneurysm treatment. TEVAR is a less invasive procedure that can
      be performed under local anesthesia with shorter hospital stay. The perioperative
      morbidity and mortality rates are lower for endovascular than open repair, but
      the rate of secondary interventions is higher for TEVAR. We report a case of an
      elderly man with synchronous abdominal and thoracic aortic aneurysms. A type III
      dangerous endoleak was recognized 3 years after TEVAR. It was successfully
      repaired during an endovascular procedure. There were no new endoleaks after 12
      months of follow-up. TEVAR may be the only option of treatment for risky and
      elderly patients. However, postoperative monitoring is necessary to exclude
      different types of endoleaks. Most of them undergo effective endovascular repair.

PMID- 29062458
TI  - Bariatric surgery and incidental gastrointestinal stromal tumors - a single
      center study: VSJ Competition, 1st place.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GISTs), originating from Cajal
      cells, are most commonly located in the stomach; therefore they can be found in
      the specimens excised during bariatric operations. The global prevalence of GISTs
      is about 130 cases per million population. Morbidity differs depending on
      geographical latitude. Although surgery is the treatment of choice for GISTs, 40
      50% of patients after radical surgical treatment will have a relapse or
      metastases. AIM: To analyze the incidence of GISTs in patients undergoing
      bariatric surgery and to verify whether an operation performed according to the
      bariatric protocol is oncologically radical in case of GIST. MATERIAL AND
      METHODS: A single-center retrospective study. The study group comprised 1252
      obese patients qualified for bariatric procedures, with no upper gastrointestinal
      tract neoplasms found during preoperative diagnostic examinations. In case of
      suspicious macroscopic pathologies (n = 81) present during the operation, tissue
      specimens underwent histopathological examination with further investigation
      performed if GISTs were found, including tumor size and localization, mitotic
      index and immunohistochemical analysis. RESULTS: Gastrointestinal stromal tumors
      were found in 16 cases, and benign tumors of various histological origin in 33
      cases. All cases of GIST found came from stomach specimens, 7 from the gastric
      corpus vs. 9 from the fundus. Fourteen GISTs were found during laparoscopic
      sleeve gastrectomies (LSGs) vs. 2 during laparoscopic Roux-en-Y gastric bypasses
      (LRYGBs). CONCLUSIONS: In case of incidental findings of GISTs during bariatric
      surgery, tumor resection with negative margins of incision may be considered as
      complete oncological treatment if there was very low/low risk stratification of
      GIST's recurrence after surgery.

PMID- 29062459
TI  - Comparison of the effects of spinal epidural and general anesthesia on
      coagulation and fibrinolysis in laparoscopic cholecystectomy: a randomized
      controlled trial: VSJ Competition, 2nd place.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) is usually performed under
      general anesthesia. Recently, laparoscopic cholecystectomy under regional
      anesthesia has become popular, but this creates a serious risk of thromboembolism
      because of pneumoperitoneum, anesthesia technique, operative positioning, and
      patient-specific risk factors. AIM: This randomized controlled trial compares the
      effects of two different anesthesia techniques in laparoscopic cholecystectomy on
      coagulation and fibrinolysis. MATERIAL AND METHODS: This randomized prospective
      study included 60 low-risk patients with deep vein thrombosis (DVT) who underwent
      elective LC without thrombo-emboli prophylaxis. The patients were randomly
      divided into two groups according to the anesthesia technique: the general
      anesthesia (group 1, n = 30) and spinal epidural anesthesia (group 2, n = 30)
      groups. Measurement of the prothrombin time (PT), thrombin time (TT),
      international normalized ratio (INR), activated partial thromboplastin time
      (aPTT), and blood levels of D-dimer (DD) and fibrinogen (F) were recorded
      preoperatively (pre), at the first hour (post 1) and 24 h (post 24) after the
      surgery. These results were compared both between and within the groups. RESULTS:
      The mean age was 51.5 +/-16.7 years (range: 19-79 years). Pneumoperitoneum time
      was similar between group 1 (33.8 +/-7.8) and group 2 (34.8 +/-10.4). The TT
      levels significantly declined postoperatively in both groups. The levels of PT,
      aPTT, INR, D-dimer and fibrinogen dramatically increased postoperatively in both
      groups. CONCLUSIONS: While there was not any DVT, there was a significant decline
      in TT. There was a dramatic rise in the PT, INR, D-dimer, fibrin degradation
      products (FDP), and fibrinogen following LC. This may be attributed to the
      effects of pneumoperitoneum and anesthesia techniques on portal vein flow.

PMID- 29062460
TI  - Heterotopic Ossification Encountered During a Complex Ventral Hernia Repair: Case
      Report and Literature Review.
AB  - Introduction: Heterotopic ossification involves the formation of trabecular bone
      outside of its usual anatomic location. While it is a well-known entity in
      orthopedic and spinal injury literature, it has also been observed after midline
      laparotomy and severe burns. Methods/Case Report: We present a case of a 69-year
      old man who presented for ventral hernia repair after a prolonged postoperative
      course following colectomy involving an open abdomen with eventual closure with
      skin grafting. Results: Two large calcified objects were encountered during the
      excision of the skin graft from the small intestine and during the component
      separation. They had grown into the anterior fascia and rectus muscle and
      interdigitated between loops of the small bowel. After careful resection of the 2
      calcified objects, a ventral hernia repair with a component separation was
      successfully performed. Pathology was consistent with heterotopic ossification.
      After 18 months, there was no clinical evidence of recurrence. Discussion:
      Heterotopic ossification is not frequently encountered during ventral hernia
      repairs, but its presence can complicate repair. Resection is the only option in
      the context of hernia repair. If recognized preoperatively, waiting up to a year
      for the bone to mature before excision has been suggested, but there is minimal
      data to support this. Consultation with a general surgeon is also advised in case
      the calcified tissue involves the underlying viscera.

PMID- 29062461
TI  - An Analysis of Malpractice Litigation and Expert Witnesses in Plastic Surgery.
AB  - Objective: Expert witness testimony is crucial for juror decision making. The
      goals of this study were to examine the trends in malpractice litigation in
      plastic surgery and to examine the characteristics of expert witnesses in
      litigation. Methods: The Westlaw legal database was queried for jury verdict and
      settlement reports related to plastic surgery cases from 2009 to 2015. Cases were
      examined for expert witness testimony, procedure performed, alleged injury, cause
      of action, verdict, and indemnity payments. Results: Ninety-three relevant cases
      were examined. Mean plaintiff award was $1,036,469, whereas mean settlement was
      $633,960. The most commonly litigated procedures involved breast surgery (34.4%),
      liposuction (18.3%), and body contouring (14.0%). Cases involving body contouring
      (risk ratio [RR] = 1.48; 95% CI, 1.04-2.10) were more likely to result in favor
      of the defendant, whereas cases involving breast surgery (RR = 0.27; 95% CI, 0.13
      0.57) were more likely to result in favor of the plaintiff (P < .05). Cases in
      which there was claimed pain (RR = 1.22; 95% CI, 1.01-1.48) or emotional distress
      (RR = 1.38; 95% CI, 1.11-1.70) were more likely to result in favor of the
      plaintiff (P < .05). The party of a lawsuit was more likely to win the case if
      its expert witness was a plastic surgeon (P < .05). Conclusion: Plastic surgery
      litigation tends to favor defendants. Most litigation involves breast surgery,
      liposuction, and body contouring. The type of procedure and alleged claim affect
      case success. Parties with a plastic surgeon as an expert witness tend to be more
      successful in litigation.

PMID- 29062462
TI  - A Simple and Safe Method to Create a Drainage Hole for Thick Skin Grafts.

PMID- 29062463
TI  - Antioxidant Treatment Reduces Formation of Structural Cores and Improves Muscle
      Function in RYR1Y522S/WT Mice.
AB  - Central core disease (CCD) is a congenital myopathy linked to mutations in the
      ryanodine receptor type 1 (RYR1), the sarcoplasmic reticulum Ca2+ release channel
      of skeletal muscle. CCD is characterized by formation of amorphous cores within
      muscle fibers, lacking mitochondrial activity. In skeletal muscle of RYR1Y522S/WT
      knock-in mice, carrying a human mutation in RYR1 linked to malignant hyperthermia
      (MH) with cores, oxidative stress is elevated and fibers present severe
      mitochondrial damage and cores. We treated RYR1Y522S/WT mice with N
      acetylcysteine (NAC), an antioxidant provided ad libitum in drinking water for
      either 2 or 6 months. Our results show that 2 months of NAC treatment starting at
      2 months of age, when mitochondrial and fiber damage was still minimal, (i)
      reduce formation of unstructured and contracture cores, (ii) improve muscle
      function, and (iii) decrease mitochondrial damage. The beneficial effect of NAC
      treatment is also evident following 6 months of treatment starting at 4 months of
      age, when structural damage was at an advanced stage. NAC exerts its protective
      effect likely by lowering oxidative stress, as supported by the reduction of 3-NT
      and SOD2 levels. This work suggests that NAC administration is beneficial to
      prevent mitochondrial damage and formation of cores and improve muscle function
      in RYR1Y522S/WT mice.

PMID- 29062466
TI  - SEGMENTATION OF ORGANS AT RISK IN THORACIC CT IMAGES USING A SHARPMASK
      ARCHITECTURE AND CONDITIONAL RANDOM FIELDS.
AB  - Cancer is one of the leading causes of death worldwide. Radiotherapy is a
      standard treatment for this condition and the first step of the radiotherapy
      process is to identify the target volumes to be targeted and the healthy organs
      at risk (OAR) to be protected. Unlike previous methods for automatic segmentation
      of OAR that typically use local information and individually segment each OAR, in
      this paper, we propose a deep learning framework for the joint segmentation of
      OAR in CT images of the thorax, specifically the heart, esophagus, trachea and
      the aorta. Making use of Fully Convolutional Networks (FCN), we present several
      extensions that improve the performance, including a new architecture that allows
      to use low level features with high level information, effectively combining
      local and global information for improving the localization accuracy. Finally, by
      using Conditional Random Fields (specifically the CRF as Recurrent Neural Network
      model), we are able to account for relationships between the organs to further
      improve the segmentation results. Experiments demonstrate competitive performance
      on a dataset of 30 CT scans.

PMID- 29062464
TI  - Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes
      by Reducing Oxidative Stress in Muscle.
AB  - Oxidative stress has been proposed to play a key role in malignant hyperthermia
      (MH), a syndrome caused by excessive Ca2+ release in skeletal muscle. Incidence
      of mortality in male calsequestrin-1 knockout (CASQ1-null) mice during exposure
      to halothane and heat (a syndrome closely resembling human MH) is far greater
      than that in females. To investigate the possible role of sex hormones in this
      still unexplained gender difference, we treated male and female CASQ1-null mice
      for 1 month, respectively, with Premarin (conjugated estrogens) and leuprolide
      (GnRH analog) and discovered that during exposure to halothane and heat Premarin
      reduced the mortality rate in males (79-27% and 86-20%), while leuprolide
      increased the incidence of mortality in females (18-73% and 24-82%). We then
      evaluated the (a) responsiveness of isolated muscles to temperature and caffeine,
      (b) sarcoplasmic reticulum (SR) Ca2+ release in single fibers, and (c) oxidative
      stress and the expression levels of main enzymes involved in the regulation of
      the redox balance in muscle. Premarin treatment reduced the temperature and
      caffeine sensitivity of EDL muscles, normalized SR Ca2+ release, and reduced
      oxidative stress in males, suggesting that female sex hormones may protect mice
      from lethal hyperthermic episodes by reducing both the SR Ca2+ leak and oxidative
      stress.

PMID- 29062467
TI  - Correction: COTI-2, a novel small molecule that is active against multiple human
      cancer cell lines in vitro and in vivo.
AB  - [This corrects the article DOI: 10.18632/oncotarget.9133.].

PMID- 29062465
TI  - NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial
      Ischemia/Reperfusion Injury in Diabetic Rats.
AB  - The reactive oxygen species- (ROS-) induced nod-like receptor protein-3 (NLRP3)
      inflammasome triggers sterile inflammatory responses and pyroptosis, which is a
      proinflammatory form of programmed cell death initiated by the activation of
      inflammatory caspases. NLRP3 inflammasome activation plays an important role in
      myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated
      whether diabetes aggravated MI/R injury through NLRP3 inflammasome-mediated
      pyroptosis. Type 1 diabetic rat model was established by intraperitoneal
      injection of streptozotocin (60 mg/kg). MI/R was induced by ligating the left
      anterior descending artery (LAD) for 30 minutes followed by 2 h reperfusion. H9C2
      cardiomyocytes were exposed to high glucose (HG, 30 mM) conditions and
      hypoxia/reoxygenation (H/R) stimulation. The myocardial infarct size, CK-MB, and
      LDH release in the diabetic rats subjected to MI/R were significantly higher than
      those in the nondiabetic rats, accompanied with increased NLRP3 inflammasome
      activation and increased pyroptosis. Inhibition of inflammasome activation with
      BAY11-7082 significantly decreased the MI/R injury. In vitro studies showed
      similar effects, as BAY11-7082 or the ROS scavenger N-acetylcysteine, attenuated
      HG and H/R-induced H9C2 cell injury. In conclusion, hyperglycaemia-induced NLRP3
      inflammasome activation may be a ROS-dependent process in pyroptotic cell death,
      and NLRP3 inflammasome-induced pyroptosis aggravates MI/R injury in diabetic
      rats.

PMID- 29062468
TI  - Assessment of the Nurse Medication Administration Workflow Process.
AB  - This paper presents findings of an observational study of the Registered Nurse
      (RN) Medication Administration Process (MAP) conducted on two comparable medical
      units in a large urban tertiary care medical center in Columbia, South Carolina.
      A total of 305 individual MAP observations were recorded over a 6-week period
      with an average of 5 MAP observations per RN participant for both clinical units.
      A key MAP variation was identified in terms of unbundled versus bundled MAP
      performance. In the unbundled workflow, an RN engages in the MAP by performing
      only MAP tasks during a care episode. In the bundled workflow, an RN completes
      medication administration along with other patient care responsibilities during
      the care episode. Using a discrete-event simulation model, this paper addresses
      the difference between unbundled and bundled workflow and their effects on
      simulated redesign interventions.

PMID- 29062469
TI  - Participative Facility Planning for Obstetrical and Neonatal Care Processes:
      Beginning of Life Process.
AB  - Introduction. Old hospitals may promote inefficient patient care processes and
      safety. A new, functionally planned hospital presents a chance to create an
      environment that supports streamlined, patient-centered healthcare processes and
      adapts to users' needs. This study depicts the phases of a facility planning
      project for pregnant women and newborn care processes (beginning of life process)
      at Turku University Hospital. Materials and Methods. Project design reports and
      meeting documents were utilized to assess the beginning of life process as well
      as the work processes of the Women's and Children's Hospital. Results. The main
      elements of the facility design (FD) project included rigorous preparation for
      the FD phase, functional planning throughout the FD process, and setting key
      values: (1) family-centered care, (2) Lean thinking and Lean tools as the
      framework for the FD process, (3) safety, and (4) cooperation. Conclusions. A
      well-prepared FD project with sufficient insight into functional planning, Lean
      thinking, and user-centricity seemed to facilitate the actual FD process.
      Although challenges occurred, the key values were not forgone and were
      successfully incorporated into the new hospital building.

PMID- 29062470
TI  - Modelling pH-Optimized Degradation of Microgel-Functionalized Polyesters.
AB  - We establish a novel mathematical model to describe and analyze pH levels in the
      vicinity of poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate-co-N
      vinylimidazole) (VCL/AAEM/VIm) microgel-functionalized polymers during
      biodegradation. Biodegradable polymers, especially aliphatic polyesters
      (polylactide/polyglycolide/polycaprolactone homo- and copolymers), have a large
      range of medical applications including delivery systems, scaffolds, or stents
      for the treatment of cardiovascular diseases. Most of those applications are
      limited by the inherent drop of pH level during the degradation process. The
      combination of polymers with VCL/AAEM/VIm-microgels, which aims at stabilizing pH
      levels, is innovative and requires new mathematical models for the prediction of
      pH level evaluation. The mathematical model consists of a diffusion-reaction PDE
      system for the degradation including reaction rate equations and diffusion of
      acidic degradation products into the vicinity. A system of algebraic equations is
      coupled to the degradation model in order to describe the buffering action of the
      microgel. The model is validated against the experimental pH-monitored
      biodegradation of microgel-functionalized polymer foils and is available for the
      design of microgel-functionalized polymer components.

PMID- 29062471
TI  - Kids' Perceptions toward Children's Ward Healing Environments: A Case Study of
      Taiwan University Children's Hospital.
AB  - This paper summarizes the opinions of experts who participated in designing the
      environment of a children's hospital and reports the results of a questionnaire
      survey conducted among hospital users. The grounded theory method was adopted to
      analyze 292 concepts, 79 open codes, 25 axial codes, and 4 selective codes; in
      addition, confirmatory factor analysis and reliability analysis were performed to
      identify elements for designing a healing environment in a children's hospital,
      and 21 elements from 4 dimensions, namely, emotions, space design, interpersonal
      interaction, and pleasant surroundings, were determined. Subsequently, this study
      examined the perceptions of 401 children at National Taiwan University Children's
      Hospital. The results revealed that, regarding the children's responses to the
      four dimensions and their overall perception, younger children accepted the
      healing environment to a significantly higher degree than did older children. The
      sex effect was significant for the space design dimension, and it was not
      significant for the other dimensions.

PMID- 29062472
TI  - Cross-linguistic phonotactic competition and cognitive control in bilinguals.
AB  - The current study examines the relation between cognitive control and linguistic
      competition resolution at the sublexical level in bilinguals. Twenty-one Spanish
      English bilinguals and 23 English monolinguals completed a non-linguistic Stroop
      task (indexing inhibitory control) and a linguistic priming/lexical decision task
      (indexing Spanish phonotactic constraint competition during English
      comprehension). More efficient Stroop performance (i.e., a smaller Stroop effect)
      in bilinguals was associated with decreased competition from Spanish phonotactic
      constraints during English comprehension. This relation was observed when nonword
      targets overlapped in phonotactic constraints and phonological form with
      preceding cognate primes (e.g., prime: stable (Spanish: estable)/target:
      esteriors). Findings suggest a link between non-linguistic cognitive control and
      co-activation of linguistic structures at the sublexical level in bilinguals.

PMID- 28928939
TI  - Towards a systematic assessment of assay interference: Identification of
      extensively tested compounds with high assay promiscuity.
AB  - A large-scale statistical analysis of hit rates of extensively assayed compounds
      is presented to provide a basis for a further assessment of assay interference
      potential and multi-target activities. A special feature of this investigation
      has been the inclusion of compound series information in activity analysis and
      the characterization of analog series using different parameters derived from
      assay statistics. No prior knowledge of compounds or targets was taken into
      consideration in the data-driven study of analog series. It was anticipated that
      taking large volumes of activity data, assay frequency, and assay overlap
      information into account would lead to statistically sound and chemically
      meaningful results. More than 6000 unique series of analogs with high hit rates
      were identified, more than 5000 of which did not contain known interference
      candidates, hence providing ample opportunities for follow-up analyses from a
      medicinal chemistry perspective.

PMID- 28580127
TI  - Improving agricultural knowledge management: The AgTrials experience.
AB  - Background: Opportunities to use data and information to address challenges in
      international agricultural research and development are expanding rapidly. The
      use of agricultural trial and evaluation data has enormous potential to improve
      crops and management practices. However, for a number of reasons, this potential
      has yet to be realized. This paper reports on the experience of the AgTrials
      initiative, an effort to build an online database of agricultural trials applying
      principles of interoperability and open access. Methods: Our analysis evaluates
      what worked and what did not work in the development of the AgTrials information
      resource. We analyzed data on our users and their interaction with the platform.
      We also surveyed our users to gauge their perceptions of the utility of the
      online database. Results: The study revealed barriers to participation and
      impediments to interaction, opportunities for improving agricultural knowledge
      management and a large potential for the use of trial and evaluation data. 
      Conclusions: Technical and logistical mechanisms for developing interoperable
      online databases are well advanced.  More effort will be needed to advance
      organizational and institutional work for these types of databases to realize
      their potential.

PMID- 28868135
TI  - Improved deconvolution of very weak confocal signals.
AB  - Deconvolution is typically used to sharpen fluorescence images, but when the
      signal-to-noise ratio is low, the primary benefit is reduced noise and a smoother
      appearance of the fluorescent structures. 3D time-lapse (4D) confocal image sets
      can be improved by deconvolution. However, when the confocal signals are very
      weak, the popular Huygens deconvolution software erases fluorescent structures
      that are clearly visible in the raw data. We find that this problem can be
      avoided by prefiltering the optical sections with a Gaussian blur. Analysis of
      real and simulated data indicates that the Gaussian blur prefilter preserves
      meaningful signals while enabling removal of background noise. This approach is
      very simple, and it allows Huygens to be used with 4D imaging conditions that
      minimize photodamage.

PMID- 29062476
TI  - Building Diversified Multiple Trees for classification in high dimensional noisy
      biomedical data.
AB  - PURPOSE: It is common that a trained classification model is applied to the
      operating data that is deviated from the training data because of noise. This
      paper will test an ensemble method, Diversified Multiple Tree (DMT), on its
      capability for classifying instances in a new laboratory using the classifier
      built on the instances of another laboratory. METHODS: DMT is tested on three
      real world biomedical data sets from different laboratories in comparison with
      four benchmark ensemble methods, AdaBoost, Bagging, Random Forests, and Random
      Trees. Experiments have also been conducted on studying the limitation of DMT and
      its possible variations. RESULTS: Experimental results show that DMT is
      significantly more accurate than other benchmark ensemble classifiers on
      classifying new instances of a different laboratory from the laboratory where
      instances are used to build the classifier. CONCLUSIONS: This paper demonstrates
      that an ensemble classifier, DMT, is more robust in classifying noisy data than
      other widely used ensemble methods. DMT works on the data set that supports
      multiple simple trees.

PMID- 29062477
TI  - Bartholin's gland abscess in a prepubertal female: A case report.
AB  - Bartholin's gland abscess is one of the common inflictions of vulva seen in
      females of reproductive age group with a recurrence rate of up to 38%. Although
      it's encountered by many Paediatric Surgeons, it's very rarely reported in
      prepubertal age. Till date, only six cases have been reported to the best of our
      knowledge. A seven-year-old female child presented with a recurrent labial
      abscess. She was found to have Bartholin's gland abscess and was treated with
      partial excision of cyst wall along with the overlying mucosa and drainage. There
      has been no recurrence for the past six months at follow-up. Bartholin's gland
      abscess, although rare in children, should be considered as one of the
      differential diagnosis of a labial swelling. Adequate drainage is essential to
      prevent recurrence.

PMID- 29062478
TI  - Mesenchymal stem cells in human meniscal regeneration: A systematic review.
AB  - BACKGROUND: Stem cell regeneration is the holy grail of meniscal tissue repair.
      Currently, the best treatment is to preserve the original meniscus but if it
      fails, a partial meniscectomy is indicated to delay the onset of osteoarthritis.
      MATERIALS AND METHODS: The authors present a systematic review to determine the
      up-to-date evidence underlying the use of mesenchymal stem cells for meniscal
      regeneration in humans. A search was conducted using the electronic databases of
      MEDLINE/Pubmed, Google scholar, and the Cochrane Collaboration. Search keywords
      included human, meniscus, stem cells and regeneration. RESULTS: After screening
      10 non-duplicate studies, 5 were identified based on title and abstract. 4 were
      included in the analysis. There were marked differences in the method of stem
      cell harvest techniques. 3 studies administered stem cells through percutaneous
      injection into the knee and 1 study used a collagen scaffold. MRI analysis,
      functional scores and safety were assessed and the longest follow-up period was 2
      years. The Visual Analogue Score (VAS) was most commonly used to assess function
      and patients generally showed an improvement. There were no reported adverse
      events. CONCLUSION: Despite positive results from animal models, there is
      currently a lack of evidence in humans to conclude that stem cells can form
      durable neotissue similar to original human meniscus. There is a need for
      standardisation of protocol before further trials are considered. Initial
      outcomes from human studies are promising and mesenchymal stem cells may play an
      important role in meniscal repair in years to come.

PMID- 29062479
TI  - Murine genotype impacts pancreatitis severity and systemic inflammation: An
      experimental study.
AB  - BACKGROUND: Little is known regarding the impact of host response in acute
      pancreatitis. Here, we induce murine necrotizing pancreatitis in 9 different
      mouse strains. MATERIALS AND METHODS: We examined 9 different mouse strains:
      Balb/CB4J, C3H/HEJ, NOD/SHILT, A/J, AKR/J, C57BI/6J, DBA/2J, FVB/NJ, 129S1/SvlmJ.
      10 animals per strain were randomly allotted to two groups. Sterile necrotizing
      pancreatitis was induced by injection of taurocholate into the common bile duct.
      Control animals were injected with saline. Every 6 h, clinical parameters were
      examined and scored. After 24 h, animals were sacrificed to examine and compare
      serum enzymes, histology, bronchoalveolar lavage fluid, and serum IL-6. RESULTS:
      Histologically, taurocholate treated animals scored significantly higher than
      control animals. Concordantly, serum lipase and amylase were significantly
      elevated in pancreatitis animals in all strains. NOD/SHILT and AKR/J mice had the
      highest enzyme activity. 24 h after induction, there were no signs of increased
      pulmonary vascular leak in taurocholate animals. Remarkably, interleukin 6 was
      not increased at all in C57BL/6J, C3H/HeJ, and 129S1/SvlmJ mice compared to all
      other strains. CONCLUSION: The genetic strain has an impact on pancreatitis
      severity and systemic inflammatory response in a murine taurocholate induction
      model. Analogous differences in humans may partially account for the disparity in
      post-ERCP pancreatitis.

PMID- 29062480
TI  - In-hospital surgical treatment for haemorrhage after aesthetic mandibular
      osteotomy performed as an office-based day surgery: A case report.
AB  - In East Asia, a square face is considered unattractive, and mandibular contouring
      surgery is commonly used to give a smooth contour to the lower jaw. Mandibular
      contouring surgery occasionally involves not only osteotomy of the mandibular
      angle but also resection of the masseter muscle via an intraoral approach. This
      type of mandibular contouring surgery poses a risk of injury to the premasseteric
      branch of the facial artery and massive haemorrhage. Here we report a patient who
      presented to our hospital with severe haemorrhage, swelling and airway
      constriction after bilateral mandibular angle and plane osteotomy with resection
      of the masseter muscle performed elsewhere as an office-based day surgery. The
      swelling and haemorrhage were treated successfully with emergency bilateral
      ligation of the facial artery and vein under general anaesthesia. We concluded
      that the haemorrhage was caused by rupture of the premasseteric branch of the
      facial artery during the resection of the masseter muscle in a day surgery.

PMID- 29062481
TI  - Surgical and nonsurgical outcomes for treating a cohort of empyema thoracis
      patients: A monocenteric retrospective cohort study.
AB  - BACKGROUND: There are several studies reporting high success rates for surgical
      and nonsurgical treatments of empyema separately. The aim of current
      retrospective cohort study is to find the best treatment in low socio-economic
      areas. MATERIAL AND METHODS: A total of 149 patients were treated in the
      referring hospital from January 2002 to December 2008. The current retrospective
      cohort study was carried out by nonsurgical (medically & thoracenthesis & chest
      tube drainage with or without fibrinolytic agents) and surgical (VATS &open
      thoracotomy decortication methods) procedures in single center performed in
      thoracic and respiratory medicine wards. The independent t-test on demographic
      data was the statistical test tool. RESULTS: The complete cure and mortality
      rates for 130 patients were 27% (35 out of 130 patients) and 0.3% (1 out of 130
      patients), respectively. Thirteen out of 149 patients that were estimated to be
      at stage II underwent VATS decortication. The results showed zero success rates
      for this procedure which was then converted to open thoracotomy decortication.
      And, 113 patients who underwent thoracotomy decortication had a cure rate of
      96.4% (109 patients) and mortality rate of 1.8% (2 patients). Four (3.5%)
      patients needed thoracoplasty, 2 died and 2 (1.8%) needed open window
      thoracostomy resulted in empyema necessitans that remained uncured. Total
      hospitalization lengths for the patients treated by tube thoracostomy and
      thoracotomy decortication were (15.4 +/- 2.1) and (6.2 +/- 1.8) days (P < 0.001),
      respectively. The success rates between surgical and nonsurgical treatments were
      98.2% and 27.1%. And, the difference between them was significant (P < 0.001).
      CONCLUSION: Because of the advanced stages of empyema in our patients,
      thoracotomy decortication procedure is often the first rank choice with success
      rates higher than nonsurgical techniques. However, nowadays, the success rates of
      nonsurgical and VATS management of empyema thoracis are mostly reported in the
      literature.

PMID- 29062482
TI  - Ocular tuberculosis in Hospital Universiti Sains Malaysia - A case series.
AB  - INTRODUCTION: Ocular tuberculosis (TB) encompasses a broad spectrum of clinical
      manifestations affecting different structures of the eye. It is caused by
      Mycobacterium tuberculosis, a great ancient organism that induces various types
      of diseases and unfavorable outcomes if unrecognized and not well treated.
      PURPOSE: To report the clinical profile of 34 ocular TB cases observed during 6
      years period in Hospital Universiti Sains Malaysia (HUSM). METHOD: A
      retrospective review of medical records from 34 patients diagnosed with ocular TB
      in HUSM from January 2011 until December 2016. RESULTS: The mean age was 43 +/-
      14.6 years old. Both male and female affected in about 1:1 ratio. The majority of
      subjects were local Malays (91.2%). Risk factors included previous contact with
      pulmonary TB patients (38.2%), and patients with underlying diabetes mellitus
      (26.5%). Most patients showed normal chest radiography (79.4%). However they had
      positive Mantoux test (94.1%) and raised erythrocyte sedimentation rate (ESR)
      value (58.8%). Uveitis was the most common ocular manifestation of ocular TB
      (70.6%) while the rare ocular manifestations included optic perineuritis and
      optic neuritis, orbital apex syndrome, orbital cellulitis, sclerokeratitis,
      corneal ulcer and conjunctival abscess. All patients responded well to anti-TB
      treatment, but visual outcome was variable. CONCLUSIONS: This review shows the
      diverse entity of ocular TB spectrum in an endemic area. Good clinical response
      to anti-tuberculous therapy supported the presumed diagnosis of ocular TB in
      majority of the cases.

PMID- 29062483
TI  - A Highly Stretchable and Robust Non-fluorinated Superhydrophobic Surface.
AB  - Superhydrophobic surface simultaneously possessing exceptional stretchability,
      robustness, and non-fluorination is highly desirable in applications ranging from
      wearable devices to artificial skins. While conventional superhydrophobic
      surfaces typically feature stretchability, robustness, or non-fluorination
      individually, co-existence of all these features still remains a great challenge.
      Here we report a multi-performance superhydrophobic surface achieved through
      incorporating hydrophilic micro-sized particles with pre-stretched silicone
      elastomer. The commercial silicone elastomer (Ecoflex) endowed the resulting
      surface with high stretchability; the densely packed micro-sized particles in
      multi-layers contributed to the preservation of the large surface roughness even
      under large strains; and the physical encapsulation of the microparticles by
      silicone elastomer due to the capillary dragging effect and the chemical
      interaction between the hydrophilic silica and the elastomer gave rise to the
      robust and non-fluorinated superhydrophobicity. It was demonstrated that the as
      prepared fluorine-free surface could preserve the superhydrophobicity under
      repeated stretching-relaxing cycles. Most importantly, the surface's
      superhydrophobicity can be well maintained after severe rubbing process,
      indicating wear-resistance. Our novel superhydrophobic surface integrating
      multiple key properties, i.e. stretchability, robustness, and non-fluorination,
      is expected to provide unique advantages for a wide range of applications in
      biomedicine, energy, and electronics.

PMID- 29062485
TI  - Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total
      thyroidectomy.
AB  - : We report a patient with Graves' disease who remained persistently hyperthyroid
      after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5
      months after surgery. She was subsequently found to have a mature cystic teratoma
      containing struma ovarii after undergoing a total hysterectomy and salpingo
      oophorectomy for an incidental ovarian lesion. LEARNING POINTS: It is important
      to investigate for other causes of primary hyperthyroidism when thyrotoxicosis
      persists after total thyroidectomy.TSH receptor antibody may persist after total
      thyroidectomy and may potentially contribute to the development of de novo
      Graves' ophthalmopathy.

PMID- 29062487
TI  - Challenges in the identification of Chryseobacterium indologenes and
      Elizabethkingia meningoseptica in cases of nosocomial infections and patients
      with cystic fibrosis.
AB  - Rare nonfermenting Gram-negative bacilli, such as Chryseobacterium indologenes
      and Elizabethkingia meningoseptica, have clinical importance in nosocomial
      infections and cystic fibrosis (CF), and their identification is a challenge to
      microbiology laboratories. Thus, the objective of this study was to verify the
      performance of phenotypic and mass spectrometry (matrix-assisted desorption
      ionization-time of flight mass spectrometry, MALDI-TOF MS) methods to identify C.
      indologenes and E. meningoseptica. In this context, the results obtained with
      phenotypic methods-namely manual biochemical and automated VITEK 2 (bioMerieux,
      Marcy l'Etoile, France) and Phoenix tests (Becton Dickinson (BD), San Diego, CA,
      USA)-and by MALDI-TOF MS-namely MALDI-TOF VITEK MS (MALDI-MS; bioMerieux) and
      MALDI-TOF BioTyper (MALDI-BD; BD)-of 22 isolates (blood cultures of patients with
      nosocomial infection (n = 15) and from patients with CF (n = 7)), initially
      identified as C. indologenes and E. meningoseptica, were compared. As result,
      using the manual phenotypic method, it was possible to identify the species level
      in 18/22; no identification was found in 4/22. There was a low agreement level
      between manual and VITEK 2 automated phenotypic methods when considering the
      genus level. The greatest agreement for genus-level identification occurred in
      MALDI-TOF MS equipment (15/22). When comparing all methods to identify the 22
      isolates, there was agreement of 4/22 at the genus level and of 4/22 at the
      species level. In conclusion, there is low agreement level among identification
      methods of C. indologenes and E. meningoseptica. Although MALDI-TOF MS equipment
      shows a higher agreement level among them, results present low levels of
      confidence.

PMID- 29062484
TI  - Weak Bond-Based Injectable and Stimuli Responsive Hydrogels for Biomedical
      Applications.
AB  - Here we define hydrogels crosslinked by weak bonds as physical hydrogels. They
      possess unique features including reversible bonding, shear thinning and stimuli
      responsiveness. Unlike covalently crosslinked hydrogels, physical hydrogels do
      not require triggers to initiate chemical reactions for in situ gelation. The
      drug can be fully loaded in a pre-formed hydrogel for delivery with minimal cargo
      leakage during injection. These benefits make physical hydrogels useful as
      delivery vehicles for applications in biomedical engineering. This review focuses
      on recent advances of physical hydrogels crosslinked by weak bonds: hydrogen
      bonds, ionic interactions, host-guest chemistry, hydrophobic interactions,
      coordination bonds and pi-pi stacking interactions. Understanding the principles
      and the state of the art of gels with these dynamic bonds may give rise to
      breakthroughs in many biomedical research areas including drug delivery and
      tissue engineering.

PMID- 29062486
TI  - Cardiac tamponade in a patient with autoimmune polyglandular syndrome type 2.
AB  - : We describe a case of a 40-year-old woman who was admitted to the intensive
      care unit with a rapid onset of dyspnea and orthopnea. She presented progressive
      weakness, weight loss and secondary amenorrhea during last year, while
      intermittent fever was present for the last two months. Initial biochemical
      evaluation showed anemia, hyponatremia and increased C-reactive protein levels.
      Clinical and echocardiographic evaluation revealed cardiac tamponade, which was
      treated with pericardiocentesis. Pleural fluid samples were negative for
      malignancy, tuberculosis or bacterial infection. Hormonal and serologic
      evaluation led to the diagnosis of autoimmune polyglandular syndrome (APS) type 2
      (including primary adrenal insufficiency and autoimmune thyroiditis), possibly
      coexisting with systemic lupus erythematosus. After symptomatic rheumatologic
      treatment followed by replacement therapy with hydrocortisone and
      fludrocortisone, the patient fully recovered. In patients with the combination of
      polyserositis, cardiac tamponade and persistent hyponatremia, possible
      coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal
      insufficiency, should be considered. Early diagnosis and non-invasive treatment
      can be life-saving. LEARNING POINTS: In patients with the combination of
      polyserositis, cardiac tamponade and persistent hyponatremia, possible
      coexistence of rheumatologic and autoimmune endocrine disease, mainly adrenal
      insufficiency, should be considered.Early diagnosis and non-invasive treatment
      can be life-saving for these patients.Primary adrenal insufficiency requires
      lifelong replacement therapy with oral administration of 15-25 mg hydrocortisone
      in split doses and 50-200 ug fludrocortisone once daily.

PMID- 29062488
TI  - 'Gracilibacillus phocaeensis' sp. nov., 'Sediminibacillus massiliensis' sp. nov.
      and 'Virgibacillus ndiopensis' sp. nov., three halophilic species isolated from
      salty human stools by culturomics.
AB  - We report the isolation of three bacterial strains that could not be identified
      by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      screening. 'Gracilibacillus phocaeensis' sp. nov., 'Sediminibacillus
      massiliensis' sp. nov. and 'Virgibacillus ndiopensis' sp. nov. are halophilic
      species isolated from salty human stools by culturomics.

PMID- 29062489
TI  - Staphylococcus aureus interaction with Pseudomonas aeruginosa biofilm enhances
      tobramycin resistance.
AB  - Antimicrobial resistance is a significant threat to the treatment of infectious
      disease. Multiple mechanisms of resistance to different classes of antibiotics
      have been identified and well-studied. However, these mechanisms are studied with
      bacteria in isolation, whereas often, infections have a polymicrobial basis.
      Using a biofilm slide chamber model, we visualized the formation and development
      of clinical Pseudomonas aeruginosa biofilms in the presence of secreted
      Staphylococcus aureus exoproducts, two bacteria that commonly co-infect pediatric
      patients with cystic fibrosis. We showed that, over time, certain isolates of P.
      aeruginosa can form different biofilm architecture in the presence of S. aureus
      exoproducts. We further determined that this interaction was dependent on Psl
      produced by P. aeruginosa and staphylococcal protein A from S. aureus.
      Importantly, we identified a mechanism of antibiotic resistance to tobramycin
      that is dependent on the polymicrobial interactions between these two bacteria.
      This interaction occurred in isolates of P. aeruginosa recovered from children
      with cystic fibrosis who failed to clear P. aeruginosa following inhaled
      tobramycin treatment.

PMID- 29062490
TI  - One small step....
AB  - This editorial introduces the new, online, open-access journal Research
      Involvement and Engagement. The journal considers manuscripts on any aspect of
      the engagement or involvement of patients, carers or members of the public in
      design, delivery and dissemination of research in health or social care. We
      support the involvement of patients in the production of the journal, as co
      authors, as reviewers and as consumers of the journal, through plain English
      summaries. We want patients and the wider public to become engaged with research
      and influence its future direction. Through the co-production of the Journal, we
      wish to encapsulate the vision of "nothing about me without me". The journal of
      Research Involvement and Engagement provides a dedicated place for publication of
      research focused on public involvement and engagement, as well as a forum for
      discussion of methodological issues that will lead to increased scientific rigour
      in public involvement and to an enhanced evidence base to underpin best practice
      internationally.

PMID- 29062492
TI  - Practical considerations in improving research through public involvement.
AB  - There is huge commitment to public and patient involvement (PPI) in UK clinical
      research. Despite there being wide agreement to practice PPI and national
      guidance on the subject, there are few practical examples of how to implement PPI
      and few published models to demonstrate how it can be achieved consistently and
      constructively across a broad portfolio of studies. The Peninsula Research Bank
      demonstrates how good PPI can be effectively integrated into experimental
      medicine research.

PMID- 29062491
TI  - Patients', clinicians' and the research communities' priorities for treatment
      research: there is an important mismatch.
AB  - PLAIN ENGLISH SUMMARY: There is some evidence that there is a mismatch between
      what patients and health professionals want to see researched and the research
      that is actually done. The James Lind Alliance (JLA) research Priority Setting
      Partnerships (PSPs) were created to address this mismatch. Between 2007 and 2014,
      JLA partnerships of patients, carers and health professionals agreed on important
      treatment research questions (priorities) in a range of health conditions, such
      as Type 1 diabetes, eczema and stroke. We were interested in how much these JLA
      PSP priorities were similar to treatments undergoing evaluation and research over
      the same time span. We identified the treatments described in all the JLA PSP
      research priority lists and compared these to the treatments described in a group
      of research studies (randomly selected) registered publically. The priorities
      identified by JLA PSPs emphasised the importance of non-drug treatment research,
      compared to the research actually being done over the same time period, which
      mostly involved evaluations of drugs. These findings suggest that the research
      community should make greater efforts to address issues of importance to users of
      research, such as patients and healthcare professionals. ABSTRACT: Background
      Comparisons of treatment research priorities identified by patients and
      clinicians with research actually being done by researchers are very rare. One of
      the best known of these comparisons (Tallon et al. Relation between agendas of
      the research community and the research consumer 355:2037-40, 2000) revealed
      important mismatches in priorities in the assessment of treatments for
      osteoarthritis of the knee: researchers preferenced drug trials, patients and
      clinicians prioritised non-drug treatments. These findings were an important
      stimulus in creating the James Lind Alliance (JLA). The JLA supports research
      Priority Setting Partnerships (PSPs) of patients, carers and clinicians, who are
      actively involved in all aspects of the process, to develop shared treatment
      research priorities. We have compared the types of treatments (interventions)
      prioritised for evaluation by JLA PSPs with those being studied in samples of
      clinical trials being done over the same period. Objective We used treatment
      research priorities generated by JLA PSPs to assess whether, on average,
      treatments prioritised by patients and clinicians differ importantly from those
      being studied by researchers. Methods We identified treatments mentioned in
      prioritised research questions generated by the first 14 JLA PSPs. We compared
      these treatments with those assessed in random samples of commercial and non
      commercial clinical trials recruiting in the UK over the same period, which we
      identified using WHO's International Clinical Trials Registry Platform. Results
      We found marked differences between the proportions of different types of
      treatments proposed by patients, carers and clinicians and those currently being
      evaluated by researchers. In JLA PSPs, drugs accounted for only 18 % (23/126) of
      the treatments mentioned in priorities; in registered non-commercial trials,
      drugs accounted for 37 % (397/1069) of the treatments mentioned; and in
      registered commercial trials, drugs accounted for 86 % (689/798) of the
      treatments mentioned. Discussion Our findings confirm the mismatch first
      described by Tallon et al. 15 years ago. On average, drug trials are being
      preferenced by researchers, and non-drug treatments are preferred by patients,
      carers and clinicians. This general finding should be reflected in more specific
      assessments of the extent to which research is addressing priorities identified
      by the patient and clinician end users of research. It also suggests that the
      research culture is slow to change in regard to how important and relevant
      treatment research questions are identified and prioritised.

PMID- 29062493
TI  - Biobanking from the patient perspective.
AB  - PLAIN ENGLISH SUMMARY: Biobanks are collections of donations of biological
      material (DNA, cells, tissue etc.) and related data which are very valuable for
      research into human diseases. A variety of biobanks exist for example within
      hospitals, research institutes, pharmaceutical companies and patient
      organisations. The role of patients in biobanking is changing from being seen
      simply as donors, to actual collaborators in the design, development and the
      running of biobanks. In this article, we provide a number of examples of patients
      acting as partners at the heart of biobanking, where their voice and perspective
      is being seen and used as a valuable resource for the biobank. Our aim is that
      these examples can be used by those who work with patients in biobank-based
      research, to design future strategies for patient and public involvement in all
      biobanks. ABSTRACT: Biobanks and biobanking research plays an increasingly
      important role in healthcare research and delivery as health systems become more
      patient-centred and medicine becomes more personalised. There is also growing
      acceptance and appreciation of the value that patients, patient advocacy
      organisations and the public can bring as stakeholders in biobanking and more
      generally in research. Therefore, the importance of active, early and sustained
      engagement and involvement of patient and public representatives in biobanks will
      become increasingly relevant. Organising and facilitating patient and public
      involvement in biobanking takes considerable time and effort for all stakeholders
      involved. Therefore, for any biobank operator considering involving patients and
      the public in their biobanking activities, consideration of best practices,
      current guidance, ethical issues and evaluation of involvement will be important.
      In this article, we demonstrate that patients are much more than donors to
      biobanks-they are collaborators at the heart of biobanking with an important
      voice to identify perspective, which can be an extremely valuable resource for
      all biobanks to utilise. The case studies herein provide examples of good
      practice of patient involvement in biobanking as well as outcomes from these
      practices, and lessons learned. Our aim is to provide useful insights from these
      efforts and potential future strategies for the multiple stakeholders that work
      with patients and the public involved in biobank-based research.

PMID- 29062494
TI  - From tokenism to meaningful engagement: best practices in patient involvement in
      an EU project.
AB  - This commentary talks about patient involvement in one of the biggest EU projects
      to date-U-BIOPRED. It describes how people and carers of people with asthma have
      been able to develop and drive their input and have their voice heard among the
      >200 healthcare professional project members. Five key principles for the success
      of the patient involvement group are presented: involve early, involve deeply,
      have patients feedback on project progress, include patients in dissemination and
      help patients convey their own story. This group has been used as an example for
      other EU-funded projects, and the patient involvement group will be maintained
      after the end of the project to ensure that their experience and knowledge can
      help develop best practice in the future.

PMID- 29062495
TI  - 'Is it worth doing?' Measuring the impact of patient and public involvement in
      research.
AB  - ABSTRACT: Much of the current debate around the impact of patient/public
      involvement on research focuses on the lack of empirical data. While a number of
      systematic literature reviews have reported the various ways in which involvement
      makes a difference to research and the people involved, this evidence has been
      criticised as being weak and anecdotal. It is argued that robust evidence is
      still required. This review reflects on the use of quantitative approaches to
      evaluating impact. It concludes that the statistical evidence is weakened by not
      paying sufficient attention to the context in which involvement takes place and
      the way it is carried out. However, if scientific (systematic, quantitative,
      empirical) approaches are designed in a way to take these factors into account,
      they might not generate knowledge that is useful beyond the original context.
      Such approaches might not therefore enhance our understanding of when, why and
      how involvement makes a difference. In the context of individual research
      projects where researchers collaborate with patients/the public, researchers
      often acquire 'new' knowledge about life with a health condition. This new
      understanding can be described as experiential knowledge-'knowledge in context'
      that researchers gain through direct experience of working with patients/the
      public. On this basis, researchers' accounts of their experience potentially
      provide a source of insight and learning to influence others, in the same way
      that the patient experience helps to shape research. These accounts could be
      improved by increasing the detail provided about context and mechanism. One of
      the most important contextual factors that influence the outcome of involvement
      is the researchers themselves and the skills, assumptions, values and priorities
      they start with. At the beginning of any research project, the researchers 'don't
      know what they don't know' until they involve patients/the public. This means
      that the impact of involvement within any particular project is somewhat
      unpredictable. The answer to the question 'Is involvement worth doing?' will
      always be 'It depends'. Further exploration of the contextual and mechanistic
      factors which influence outcomes could give a stronger steer to researchers but
      may never accurately predict any specific impact. PLAIN ENGLISH SUMMARY: In
      recent years, there has been considerable interest in finding out what difference
      patient and public involvement makes to research projects. The evidence published
      so far has been criticised for being weak and anecdotal. Some people argue we
      need robust evidence of impact from scientific studies of involvement. In this
      review, I consider examples of where impact has been measured using statistical
      methods. I conclude that the statistical evidence is weak, if the studies do not
      consider the context in which involvement takes place and the way that it is
      done. Studies designed to take this into account give us more confidence that the
      involvement did make a difference to that particular project. They do not tell us
      whether the same impact will occur in the same way in other projects and
      therefore have limited value. Researchers gain an understanding of involvement
      through their direct experience of working with patients and the public. This is
      'knowledge in context' or 'insight' gained in the same way that patients gain
      expertise through their direct experience of a health condition. This means that
      detailed accounts of involvement from researchers already provide valuable
      learning to others, in the same way that patients' insights help shape research.
      However, the impact of involvement will always be somewhat unpredictable, because
      at the start of any project researchers 'don't know what they don't know'-they do
      not know precisely what problems they might anticipate, until the patients/public
      tell them.

PMID- 29062496
TI  - Missed opportunities for impact in patient and carer involvement: a mixed methods
      case study of research priority setting.
AB  - PLAIN ENGLISH SUMMARY: Healthcare workers want to listen more to patients and
      their carers in all sorts of areas of healthcare. This can include choosing
      topics for medical research. We looked at how patients and carers have helped to
      choose topics for research about type I diabetes. We aimed to find out if, and
      why, researchers often rejected their choices. We looked at a project which
      brought together patients, carers and healthcare workers to choose topics for
      research about type 1 diabetes. The group first asked patients, carers and
      healthcare workers to suggest ideas for research questions. But the group had to
      follow rules about what counted as a good research question. Some people's ideas
      did not count as good research questions, and they were rejected at the start. We
      looked at who were most likely to have their ideas rejected at the start. We
      found that patients and carers were most likely to have a suggestion rejected.
      Then we looked at the rejected questions in detail. They were mostly about curing
      diabetes, preventing diabetes and understanding how diabetes works. There were
      also some questions about access to medicines and the quality of care.
      Researchers should ask patients and carers for help deciding what counts as a
      good research question from the start of projects like these. We should also
      think about what might be getting in the way of patients and carers making more
      of a difference in research. ABSTRACT: Background Patients and carers are
      increasingly involved in deciding on topics for medical research. However, so
      far, it has been difficult to gain an accurate picture of the impact of such
      involvement because of poor reporting and evaluation in published studies to
      date. This study aimed to explore how a partnership of patients, carers,
      healthcare professionals and organisations identified questions for future
      research and why patients and carers had a limited impact on this process.
      Methods In the first stage of the partnership process, relevant service users and
      providers (including patients, carers, healthcare professionals and voluntary
      organisations) were invited to submit suggested research questions about the
      treatment of type 1 diabetes, via a national online and paper survey. The
      partnership followed formal protocols that defined a researchable question. This
      meant that many respondents' suggested research questions were rejected at the
      start of the process. We analysed survey submissions to find out which groups of
      respondents were most likely to have their suggestions rejected and what these
      suggestions were about. Results Five hundred eighty-three respondents submitted
      1143 suggested research questions, of which 249 (21.8 %) were rejected at the
      first stage. Respondents with lived experience of this long-term condition
      (patients and carers) were more likely than those without lived experience to
      submit a research question that would be rejected (35.6 vs. 16.5 %; p < 0.0005).
      Among the rejected questions submitted by patients and carers, there were several
      key themes: questions about cure, cause and prevention, understanding the
      disease, healthcare policy and economics. Conclusions In this case study, early
      decisions about what constituted a researchable question restricted patients' and
      carers' contributions to priority setting. When discussions about a project's
      remit take place before service users are involved, researchers risk distorting
      the potential impact of involvement. Impact assessments should consider not only
      the differences patients and carers make to research but also the differences
      they could have made in the absence of systemic barriers. We recommend that
      initiatives aimed at involving patients and carers in identifying research
      questions involve them as early as possible, including in decisions about how and
      why suggested research questions are selected or rejected.

PMID- 29062497
TI  - Patient and public involvement in data collection for health services research: a
      descriptive study.
AB  - PLAIN ENGLISH SUMMARY: There is a consensus that patients and the public should
      be involved in research in a meaningful way. To date, lay people have been mostly
      involved in developing research ideas and commenting on patient information but
      not as much in actual data collection. We have had firsthand experience with lay
      people helping to conduct a study on how patients in hospital are involved with
      their medicines. In the first part of this study, we observed doctors' ward
      rounds, pharmacists' ward visits and nurses' drug administration rounds, to find
      out if and how healthcare professionals interacted with patients about their
      medicines. Lay people conducted some of these observations. We wanted to explore
      the benefits and challenges of having lay people conduct these observations, to
      tell us more about how lay people can be involved in conducting such research. We
      interviewed the lay members and researchers involved in this research to find out
      their views. We also looked at the observation notes to identify what the lay
      people had noticed that the researchers had not. The lay members and researchers
      reported that lay members added value to the study by bringing new perspectives.
      Lay people had noticed some different things to the researchers. We experienced
      some challenges which need to be addressed. These weregetting the lay observers
      registered with the hospitals to allow them to be on the wards in this
      capacitylay observers and researchers having different understanding of research
      procedures such as patient consenttrying to find lay observers of different
      backgrounds and ethnic groups. ABSTRACT: Background: It is recognised that
      involving lay people with research in a meaningful rather than tokenistic way is
      both important and challenging. In a recent health services research study
      addressing inpatient involvement in medication safety, we sought to overcome this
      challenge by including lay people in collecting observational data in the
      hospital setting. The aim of this study was to evaluate lay and researcher
      perspectives on lay involvement in data collection in order to inform and enhance
      the future role of lay people in carrying out health services research. Methods:
      We conducted semi-structured interviews with the lay members who collected
      observational data in our wider study and the researchers who provided support
      and/or were involved in their recruitment and training. The interviews were
      transcribed verbatim and coded using open thematic analysis. In addition, we
      conducted secondary analysis of the observational data to identify the specific
      contributions of lay observers. Results: We interviewed the three lay members and
      the four researchers involved. Both these interviews and the secondary data
      analysis demonstrated that the lay members added value to the study by bringing
      additional general perspectives on communication with hospital inpatients.
      Combined with researchers' perspectives on interactions more specifically related
      to medication, this provided a broader answer to our research question of how
      healthcare professionals facilitate inpatient understanding of their medication
      and involvement in medication safety. This contrasted to the involvement lay
      observers reported having in previous research where their role had been more
      consultative. The lay members all reported that carrying out the observations had
      been an interesting and informative experience. Some challenges arose including
      the infrastructure not having been in place to support this specialist lay
      research role, differing paradigms of research governance held by the public and
      researchers in relation to consent procedures and difficulties in recruiting a
      diverse range of members of the public to carry out the role. Conclusions: Lay
      members can add value to research by being involved in data collection within
      health services research. There is a need to build infrastructure to better
      support this involvement.

PMID- 29062498
TI  - Researching health inequalities with Community Researchers: practical,
      methodological and ethical challenges of an 'inclusive' research approach.
AB  - PLAIN ENGLISH SUMMARY: Public health research sometimes uses members of
      communities as researchers. These are called Community Researchers. The advantage
      of using Community Researchers is that it enables people who live in communities
      to participate in research by designing the research, gathering data and being
      involved in analysis. This 'participatory' approach also has the potential to
      reach communities that might otherwise not be included in research. There are few
      studies that report the experiences of Community Researchers who take part in
      such research. This study helps fill this gap by exploring the issues and
      challenges faced by Community Researchers involved in a study of health and
      poverty in ethnically mixed areas of east London, UK. Through the accounts of 12
      researchers, the study reveals that being a community 'insider' had advantages:
      many felt they had been able to gain the trust of respondents and access people
      for the research that would have otherwise been missed. The role of Community
      Researcher was, however, difficult to manage with some researchers feeling
      burdened by their role and the increased knowledge they had about the lives of
      those in their community. In addition to the personal challenges for the
      Community Researchers, the findings raise various ethical and methodological
      issues that need consideration in participatory research. ABSTRACT: Background
      Inclusive research approaches are increasingly employed by public health
      researchers. Recent methodological development includes the engagement of
      Community Researchers (CRs), who use their knowledge and networks to facilitate
      research with the community with which they identify. Few studies have explored
      the experiences of CRs in the research process, an important element of any
      comprehensive assessment of the pros and cons of such research endeavours. We
      report here on the experiences of CRs engaged in a study of health inequalities
      and poverty in ethnically diverse and disadvantaged areas of London, UK. Methods
      We draw on the experiences of 12 CRs. Two sets of data were generated, analysed
      and integrated: debriefing/active reflection exercises throughout the 18-month
      research process and individual qualitative interviews with CRs, conducted at the
      end of the project (n = 9). Data were organised using NVivo10 and coded line-by
      line using a framework developed iteratively. Synthesis and interpretation were
      achieved through a series of reflective team exercises involving input from 4 of
      the CRs. Final consolidation of key themes was conducted by SS and ES. Results
      Being an 'insider' to the communities brought distinct advantages to the research
      process but also generated complexities. CRs highlighted how 'something would be
      lost' without their involvement but still faced challenges in gathering and
      analysing data. Some CRs found it difficult to practice reflexivity, and problems
      of ethnic stereotyping were revealed. Conflict between roles as community members
      and investigators was at times problematic. The approach promoted some aspects of
      personal empowerment, but CRs were frustrated by the limited impact of the
      research at the local level. Conclusions Working with CRs offers distinct
      practical, ethical and methodological advantages to public health researchers,
      but these are limited by a range of challenges related to 'closeness', orthodox
      research structures and practices and the complexities of dynamic identities. For
      research of this type to meet its full potential and avoid harm, there is a need
      for careful support to CRs and long-term engagement between funders, research
      institutions and communities.

PMID- 29062499
TI  - Exploring the impact of providing evidence-based medicine training to service
      users.
AB  - PLAIN ENGLISH SUMMARY: Within health services research in the UK, there has been
      growing interest in evidence-based medicine (EBM) and patient and public
      involvement (PPI) in research. These two movements have a common goal of
      improving the quality and transparency of clinical decision making. So far, there
      has been relatively little discussion about how these two movements might relate
      to each other, despite their common concern. Indeed, some in the PPI movement
      have expressed doubts about the implications of EBM for PPI because they worry
      that its emphasis on evidence from clinical trials marginalises the importance of
      a patient's individual experiences in clinical decision making. The purpose of
      this paper is to examine the potential for EBM and PPI to complement one another.
      We analysed the feedback of 10 members of the Peninsula Public Involvement Group
      (PenPIG) who attended EBM workshops. These workshops trained people in the basics
      of EBM and were primarily attended by health professionals. We used thematic
      analysis, a qualitative data analysis method, to explore the responses. We found
      that participation in the workshops appears to have increased the ability and
      confidence of members of the public to actively participate as both producers and
      consumers of research evidence. We conclude that there is an untapped potential
      for EBM and PPI to complement one another in their shared desire to improve the
      quality and transparency of clinical decision making. ABSTRACT: Background Within
      the UK, health services research in the 1990s was marked by growing interest in
      evidence-based medicine (EBM) and in the potential of patient and public
      involvement (PPI) in research. However, there has been relatively little
      discussion of how these two developments might relate to each other, despite
      their common concern to improve the quality and transparency of clinical decision
      making. Indeed, some in the user involvement movement have expressed doubts about
      the implications of EBM for PPI. The purpose of this paper is to examine the
      potential for EBM and PPI to complement one another. Methods We used a case study
      design. Fifteen EBM workshops, involving PPI members, were conducted between June
      2010 and December 2014. All 13 lay participants, who attended the first five
      workshops, were asked to fill in a standard feedback proforma designed by a
      member of the NIHR Collaboration for Leadership in Applied Health Research and
      Care for the South West Peninsula (PenCLAHRC) Public Involvement Group (PenPIG).
      Ten responses were received, and these were analysed thematically. Results Four
      themes emerged from the thematic analysis: research knowledge, research skills,
      shared clinical decision making and learning environment. Participation in the
      workshops appears to have increased the ability and confidence of members of the
      public to actively participate as both producers and consumers of research
      evidence. Conclusions There is an untapped potential for EBM and PPI to
      complement one another in their shared desire to improve the quality and
      transparency of clinical decision making.

PMID- 29062501
TI  - More than just ticking a box...how patient and public involvement improved the
      research design and funding application for a project to evaluate a cycling
      intervention for hip osteoarthritis.
AB  - PLAIN ENGLISH SUMMARY: Involving patients and the public in research helps to
      ensure that research remains relevant, and has an impact on the people it aims to
      benefit. Funding bodies now require patients and the public to be involved at all
      stages of research. Patients and members of the public were involved from the
      outset in research into a cycling and education programme for hip osteoarthritis.
      A group discussion took place with six participants from a trial of the
      programme. The group provided feedback on several areas including the relevance
      of the research, how the researchers proposed to recruit patients, the research
      design, the programme itself (including what they liked/didn't like about it),
      and how the researchers could publicise the research findings. The feedback
      received was invaluable, and helped shape the entire research project and funding
      application. The cycling and education programme has been extended in line with
      comments received from the group. They also helped identify the best way of
      gathering information from research participants and had suggestions for sharing
      the results, both of which were incorporated into the funding application. Often
      involving patients and the public in research can be seen as a 'tick box'
      exercise. However, this example shows how crucial involving patients and the
      public in research design is. It also shows how the funding application was made
      stronger as a result of patient input. Researchers should be encouraged to work
      closely with patients and the public to ensure their research is of the highest
      quality. ABSTRACT: Background Involving patients and the public in research is an
      essential activity to ensure relevant, accessible, and appropriate research.
      There is increasing obligation from funding bodies on researchers to have well
      thought through plans for involving the public, and indeed it is often a
      condition for funding. Patient and public involvement activity in this project
      was conducted to inform a funding application to investigate the effectiveness of
      a cycling and education intervention in the treatment of hip osteoarthritis.
      Methods Six participants from a feasibility programme of the intervention
      attended a two-hour patient and public involvement consultation group to provide
      feedback on various aspects of the proposed research and intervention. During the
      consultation group, two independent facilitators followed a detailed plan
      formulated with the research team. Feedback was validated by the attendees via
      email following the consultation, and a report was issued to the research team.
      Further feedback on subsequent changes was sought via email and telephone with
      members of a Patient Advisory Group. Results The patient and public involvement
      consultation group provided invaluable feedback and suggestions which impacted on
      the design and quality of the research project and the intervention. Key changes
      to the intervention included extending the duration of the cycling programme from
      six to eight weeks, and inclusion of an exercise diary to promote adherence to
      the intervention. Key feedback regarding the design of the research and funding
      application included suggestions for methods of dissemination, and confirmation
      of the primary outcome measure. Conclusions Patient and public involvement was
      crucial to the design of the proposed research and intervention. It informed many
      aspects of the research design and made the funding application stronger as a
      result. Involving patients and the public in research is much more than an
      obligation, or 'tick box' exercise. It can change and improve research quality,
      which is crucial when answering questions that are meaningful and important to
      patients, and which leads to increased impact. Collaboration with patients and
      the public should be planned and reported from the conception of a research idea
      where the impact of such input can be considerable.

PMID- 29062500
TI  - Consulting patients in setting priorities in Myalgic Encephalomyelitis (M.E.)
      research: findings from a national on-line survey.
AB  - : Myalgic encephalitis (M.E.) is a common condition, the cause of which is not
      known and there are no treatments available. In this study the national patient
      support group Action for M.E. sought the opinions of their members via an online
      survey as to what they felt should be future priorities for M.E. RESEARCH:
      Respondents were asked what they considered first, second and third research
      priorities to be from a list of 13 pre-defined options. Individuals were invited
      to provide additional free text comments about Action for M.E.'s research
      priorities in general. Of the 1144 respondents: 822 had M.E.; 94 were a
      supporting a member of Action for M.E. ; 66 were carers for someone with M.E.; 26
      were professionals with an interest in M.E.; 136 had a family member or colleague
      with M.E. Individuals selected more than one category as applicable. The top five
      research priorities identified were: disease processes to achieve a better
      understanding of the causes of M.E.; more effective treatments; faster and more
      accurate diagnosis; clinical course of M.E.; outcomes and natural history; and
      severely affected patients. Least popular priorities were: sleep; economic
      research towards identifying the cost of ME; and psychological aspects. Much of
      the free text comments emphasised the importance of funding biomedical research
      into disease processes to achieve a better understanding of the causes of M.E.
      Three themes were identified in relation to this topic: accurate diagnosis and
      awareness; risk factors and causes; drug development and curative therapies. In
      conclusion; individuals affected by M.E. have clear views regarding priorities
      for research investment. These have informed Action for M.E.'s ongoing research
      strategy and ultimately will inform national and international research
      priorities.

PMID- 29062502
TI  - Patient and public involvement in primary care research - an example of ensuring
      its sustainability.
AB  - BACKGROUND: The international literature on patient and public involvement (PPI)
      in research covers a wide range of issues, including active lay involvement
      throughout the research cycle; roles that patients/public can play; assessing
      impact of PPI and recommendations for good PPI practice. One area of
      investigation that is less developed is the sustainability and impact of PPI
      beyond involvement in time-limited research projects. METHODS: This paper focuses
      on the issues of sustainability, the importance of institutional leadership and
      the creation of a robust infrastructure in order to achieve long-term and wide
      ranging PPI in research strategy and programmes. RESULTS: We use the case of a
      Primary Care Research Centre to provide a historical account of the evolution of
      PPI in the Centre and identified a number of key conceptual issues regarding
      infrastructure, resource allocation, working methods, roles and relationships.
      CONCLUSIONS: The paper concludes about the more general applicability of the
      Centre's model for the long-term sustainability of PPI in research.

PMID- 29062505
TI  - It's not evidence, it's insight: bringing patients' perspectives into health
      technology appraisal at NICE.
AB  - PLAIN ENGLISH SUMMARY: Health technology appraisal involves reviewing the
      findings from clinical trials and economic data to produce guidance on how health
      technology should be used. This task is carried out by appraisal committees in
      NICE. One of the several ways in which patients can feed their views into these
      committees is via a written patient statement. We asked nine committee members
      about what difference the information from patients makes to their decision
      making. The Committee members reported that written patient statements offer a
      different perspective when reviewing the clinical and economic data. This can
      have a profound impact when a committee draws conclusions based solely on the
      data, which may not reflect the reality of patients' lives. The patients' and
      carers' input provides meaning to the data, 'bringing the numbers to life'. It
      identifies if the technology has any wider impacts than what's been reported in
      the clinical trial, and also if the trial has measured what's important to
      patients. We conclude that the written patient statement adds value to the
      decision-making process by helping Committee members to make sense of the
      clinical and economic data-it makes them look at the evidence 'in a different
      light'. Patients' stories are very effective in this context, because they have
      the power to communicate and to challenge Committee members' assumptions.
      Understanding this difference between analysing research evidence and drawing on
      patients' insights is important in thinking about what's needed in a written
      patient statement and the best way to obtain it. ABSTRACT: Background Health
      technology appraisal involves reviewing clinical and economic data to inform
      guidance on the use of technology. In England this task is carried out by
      appraisal committees within the National Institute for Health and Care Excellence
      (NICE). Patients are not committee members as they have a vested interest in the
      outcome, but one of the several ways they are involved is through submitting a
      written patient statement, which is considered by the committee during its
      deliberations. We aimed to find out how the written patient statement adds value
      to the decision-making process by exploring how it is used in practice. Methods
      Semi-structured interviews were conducted with nine members of NICE appraisal
      committees. The interviews were transcribed and analysed thematically. We drew on
      published evidence of the impact of patient involvement on clinical research and
      our experience of supporting organisations to produce written patient statements
      to analyse the findings. Results Committee members reported that written patient
      statements offer a different perspective when evaluating clinical and economic
      data. This can have a profound impact when a committee draws conclusions based on
      data that may not reflect the reality of the patient experience. Information from
      patients and carers also provides context and meaning to the data, by explaining
      its real-life implications. It identifies wider impacts of a technology that may
      not have been assessed in a clinical trial, as well as commenting on whether what
      has been measured in a trial is relevant to patients. The main barrier to using
      the written patient statement is the misperception that it is a form of research
      'evidence', when in fact it takes the form of experiential knowledge - or
      insight. Conclusions The written patient statement adds value by aiding Committee
      members in their interpretation of existing evidence - it enables them to
      consider this evidence 'in a different light'. In this context, patients'
      experiential knowledge is effective because it is subjective, emotional and
      anecdotal. It then has the power to communicate and to challenge assumptions
      based on the data alone. Understanding this difference between using evidence and
      insights has implications for the content of a written patient statement and the
      approaches used to obtain it.

PMID- 29062503
TI  - Older people's priorities in health and social care research and practice: a
      public engagement workshop.
AB  - PLAIN ENGLISH SUMMARY: A one day public engagement workshop was held to focus on
      the priorities of older people about research and practice in health and social
      care. Seventy-five older people from the general public and a variety of
      backgrounds attended this event to share their views and discuss what should be
      prioritised. The main aim of this workshop was to identify and prioritise issues
      that are important to older people that would benefit from further research, as
      well as create an environment for older people to share ideas and problems
      related to these important issues. Key priorities brought up by participants
      included loneliness and isolation, support and training for professional and
      family carers, post-surgical care, negative perceptions of older people and
      inequalities related to public services and healthcare. Participants further
      suggested older people should be actively involved in all stages of the research
      process. ABSTRACT: As the world's population ages, there is an increasing need
      for research that addresses the priorities of older people. A public engagement
      workshop focusing on the priorities of older people for research and practice in
      health and social care was attended by seventy-five people aged 70 years and
      above in London, United Kingdom (UK). The workshop aimed to identify and
      prioritise issues important to older people that would benefit from further
      research and act as a platform to promote sharing of ideas and problems related
      to these important issues. Key priorities emerged including loneliness and
      isolation, support and training for professional and family carers, post-surgical
      care, negative perceptions of older people and inequalities related to public
      services and healthcare. Participants further suggested older people should be
      actively involved in all stages of the research process.

PMID- 29062506
TI  - Patient-reported quality indicators for osteoarthritis: a patient and public
      generated self-report measure for primary care.
AB  - PLAIN ENGLISH SUMMARY: People with osteoarthritis desire high quality care,
      support and information. However, the quality of care for people with OA in
      general practice is not routinely collected. Quality Indicators can be used to
      benefit patients by measuring whether minimum standards of quality care are being
      met from a patient perspective. The aim of this study was to describe how a
      Research User Group (RUG) worked alongside researchers to co-produce a set of
      self-reported quality indicators for people with osteoarthritis when visiting
      their general practitioner or practice nurse (primary care). These were required
      in the MOSAICS study, which developed and evaluated a new model of supported self
      management of OA to implement the NICE quality standards for OA. This article
      describes the public involvement in the MOSAICS study. This was 1) the co
      development by RUG members and researchers of an Osteoarthritis Quality
      Indicators United Kingdom (OA QI (UK)) questionnaire for use in primary care, and
      2) the comparison of the OA QI (UK) with a similar questionnaire developed in
      Norway. This study shows how important and effective a research user group can be
      in working with researchers in developing quality care indicators for
      osteoarthritis for use in a research study and, potentially, routine use in
      primary care. The questionnaire is intended to benefit patients by enabling the
      assessment of the quality of primary care for osteoarthritis from a patient's
      perspective. The OA QI (UK) has been used to examine differences in the quality
      of osteoarthritis care in four European countries. ABSTRACT: Background People
      with osteoarthritis (OA) desire high quality care, support and information about
      OA. However, the quality of care for people with OA in general practice is not
      routinely collected. Quality Indicators (QI) can be used to benefit patients by
      measuring whether minimum standards of quality care (e.g. NICE quality standards)
      are being met from a patient perspective. A Research User Group (RUG) worked with
      researchers to co-produce a set of self-report, patient-generated QIs for OA. The
      QIs were intended for use in the MOSAICS study, which developed and evaluated a
      new model of supported self-management of OA to implement the NICE guidelines. We
      report on 1) the co-development of the OA QI (UK) questionnaire for primary care;
      and 2) the comparison of the content of the OA QI (UK) questionnaire with a
      parallel questionnaire developed in Norway for the Musculoskeletal Pain in
      Ullensaker (MUST) study. Methods Researchers were invited to OA RUG meetings.
      Firstly, RUG members were asked to consider factors important to patients
      consulting their general practitioner (GP) for OA and then each person rated
      their five most important. RUG members then discussed these in relation to a
      systematic review of OA QIs in order to form a list of OA QIs from a patient
      perspective. RUG members suggested wording and response options for a draft OA QI
      (UK) questionnaire to assess the QIs. Finally RUG members commented on draft and
      final versions of the questionnaire and how it compared with a translated
      Norwegian OA-QI questionnaire. Results RUG members (5 males, 5 females; aged 52
      80 years) attended up to four meetings. RUG members ranked 20 factors considered
      most important to patients consulting their GP for joint pain. Following
      discussion, a list of eleven patient-reported QIs for OA consultations were
      formed. RUG members then suggested the wording and response options of 16 draft
      items - four QIs were split into two or more questionnaire items to avoid
      multiple dimensions of care quality within a single item. On comparison of this
      to the Norwegian OA-QI questionnaire, RUG members commented that both
      questionnaires contained seven similar QIs. The RUG members and researchers
      agreed to adopt the Norwegian OA-QI wording for four of these items. RUG members
      also recommended adopting an additional seven items from the Norwegian OA-QI with
      some minor word changes to improve their suitability for patients in the UK. One
      other item from the draft OA QI (UK) questionnaire was retained and eight items
      were excluded, resulting in a 15-item final version. Conclusions This study
      describes the development of patient-reported quality indicators for OA primary
      care derived by members of a RUG group, working in partnership with the research
      team throughout the study. The OA QI (UK) supports the NICE quality standards for
      OA and they have been successfully used to assess the quality of OA consultations
      in primary care in the MOSAICS study. The OA QI (UK) has the potential for
      routine use in primary care to assess the quality of OA care provided to
      patients. Ongoing research using both the UK and Norwegian OA-QI questionnaires
      is assessing the self-reported quality of OA care in different European
      populations.

PMID- 29062507
TI  - The patient voice in research-evolution of a role.
AB  - PLAIN ENGLISH SUMMARY: Engaging patients in research studies is becoming more
      common because it makes research and its results more relevant for patients. It
      is important to understand the best ways for patients and researchers to work
      together. Patients who are included as active partners in research can provide
      useful input on what it is like to work on a research team but very little has
      been written about this from the patient's perspective. As patient partners and
      researchers on a breast cancer study, we share our experience to develop a
      patient-centered project and the inclusion of patient collaborators as scientific
      experts. Over time, the role of the patient partner has developed to include
      unanticipated roles and responsibilities. We use our experience to share how the
      patient voice can affect the execution of a research study and to provide a model
      for meaningfully engaging patients in research. ABSTRACT: Engaging patients in
      research studies is becoming more common because it makes research and its
      results more relevant for patients. It is important to understand the best ways
      for patients and researchers to work together. Patients who are included as
      active partners in research can provide useful input on what it is like to work
      on a research team but very little has been written about this from the patient's
      perspective. As patient partners and researchers on a breast cancer study, we
      share our experience to develop a patient-centered project and the inclusion of
      patient collaborators as scientific experts. Over time, the role of the patient
      partner has developed to include unanticipated roles and responsibilities. We use
      our experience to share how the patient voice can affect the execution of a
      research study and to provide a model for meaningfully engaging patients in
      research.

PMID- 29062508
TI  - Combining PPI with qualitative research to engage 'harder-to-reach' populations:
      service user groups as co-applicants on a platform study for a trial.
AB  - PLAIN ENGLISH SUMMARY: It is recommended that research studies are carried out
      with or by patients and the public through their involvement from the beginning
      and in as many stages as possible (known as PPI). Some studies formally invite
      patients and the public to participate in interviews and focused group
      discussions to collect views about topics (known as qualitative research). In our
      study on financial incentives for giving up smoking in pregnancy and
      breastfeeding, we combined both PPI and qualitative research to include the views
      of women with a range of experiences of smoking and breastfeeding. We involved
      two mother and baby groups in disadvantaged areas of North East Scotland and
      North West England as research partners on our team. First, we asked members to
      comment on our research plans and documents, which is standard PPI. Second, we
      asked members to participate in voice recorded discussions, contributing to
      qualitative research data. These discussions revealed different views from those
      that we heard through research interviews. They allowed us to develop more
      relevant research tools and resources. Members also helped us to identify people
      outside the groups who we could interview. Combining involvement and
      participation helped us to include the views of a wide range of women from
      'harder-to-reach' groups who don't usually take part in research. This was
      important because the research was intended for women who could benefit from
      incentives to stop smoking in pregnancy and breastfeed, often present in such
      groups. Positive continuing relationships and trust improved on involvement or
      participation alone. ABSTRACT: ?. BACKGROUND: Patient and public involvement
      (PPI) in all research studies is recommended from the earliest point and in as
      many stages as possible. Qualitative research is also recommended in the early
      stages of designing complex intervention trials. Combining both together might
      enable inclusion of 'harder-to-reach' perspectives from the target population(s),
      particularly when the research is intended for their benefit. However, the
      interface between PPI and qualitative research has received little attention. In
      a multi-disciplinary, mixed methods study to inform the design of incentive
      trials for smoking cessation in pregnancy and breastfeeding, we combined PPI and
      qualitative research, with some overlap. Mother and baby groups from two
      geographically separate disadvantaged areas, with diverse experiences of the
      smoking and breastfeeding, but no training or previous involvement in research,
      were recruited as PPI research grant co-applicants. An iterative partnership
      approach facilitated involvement in research conduct and design across all
      project phases. Group PPI members were also invited to contribute to more formal
      qualitative data collection, as and when indicated by the research questions, and
      emerging analysis. RESULTS: We engaged with 'harder-to-reach' women in mother and
      baby group settings, rather than in academic or home environments. These settings
      were relaxed and informal, which facilitated rapport-building, disclosures of
      unexpected information and maintained trust. Twenty-one women participated in
      standard PPI activities: feedback on study protocols and documents; piloting
      questionnaires and interview schedules. PPI members voiced some different
      perspectives from those captured within the qualitative dataset. Nineteen
      participated in focused qualitative research. Novel aspects were audio recorded
      PPI discussions, which contributed qualitative data; first, to interpret
      systematic review findings and construct intervention vignettes for use in the
      qualitative research; second, to assist with recruitment to improve sample
      diversity in the formal qualitative dataset; and third, to translate theory and
      findings presented in a researcher generated logic model into a lay tool. This
      had face validity for potential trial participants and used the metaphor of a
      ladder. CONCLUSIONS: Combining and overlapping PPI and qualitative research added
      'harder-to-reach' contributions, sample diversity, trust and engagement in
      creative approaches beyond what could be achieved through PPI or qualitative
      research alone.

PMID- 29062509
TI  - A SHARED study-the benefits and costs of setting up a health research study
      involving lay co-researchers and how we overcame the challenges.
AB  - PLAIN ENGLISH SUMMARY: In the United Kingdom (UK), official bodies such as the
      Department of Health and research funders such as the National Institute for
      Health Research support and encourage lay involvement in all stages of research
      studies. The SHARED study has had substantial patient and public involvement
      (PPI) from developing the idea to dissemination. The aim of the study has been to
      develop recommendations led by service users for health and social care
      professionals to use at hospital discharge and in care planning for people living
      with memory loss and their carers. This article is about how the study started
      and the benefits, costs and challenges we encountered as the lead and lay co
      researchers. Once we were successful with the grant application, we had to
      recruit and train the lay co-researchers and obtain various approvals before we
      could start the project. We had various support from funders, the Research Ethics
      Committee, lay members of Alzheimer's Society and from the lay co-researchers.
      However, we encountered some challenges with paying the lay co-researchers and
      with getting the approval for the co-researchers to interview staff on NHS
      premises. The challenges were overcome eventually but some aspects of the study
      changed because of this. We suggest that some changes could be made to the
      research system which would lead to greater inclusion of the lay co-researchers
      in research studies and would make the process more straightforward for the
      research team. ABSTRACT: Background Involving patients and the public in all
      stages of research has been the focus of the SHARED study. Patient and public
      involvement (PPI) is an important strategic priority for the Department of Health
      and funders such as the National Institute for Health Research. The aim of this
      paper is to describe the benefits, challenges and costs involved in setting up
      the research study with lay members as part of the research team. The study
      focused on developing service user-led recommendations for people with memory
      loss and their carers, on discharge from acute hospital to the community. Methods
      This began with a discussion of an initial research idea with a lay group of
      carers and people living with dementia. Once funded, approval was sought from the
      Research Ethics Committee and NHS Trusts to conduct the research including the
      active involvement of lay co-researchers. Finally, to recruit, train and pay lay
      co-researchers in their role. Results The benefits of PPI have included
      developing ideas which are important to people living with memory loss; support
      for PPI received from the funders and research ethics committee, high levels of
      interest from volunteer groups, and lasting enthusiasm from many of the co
      researchers. Organisational challenges were met in the requirement for research
      passports and with payment methods for the co-researchers. Training was
      beneficial but incurred extra costs for repeated training days. Discussion
      Overall the benefits outweighed the challenges which were overcome to varying
      degrees. The lay co-researchers gained membership of a study group and a
      beneficial partnership developed with the third sector. The biggest challenge was
      in overcoming the differences in approach to lay co-researchers between NHS
      Trusts. Organisational culture has been slow to incorporate PPI and this has not
      yet been fully addressed. It has the potential to delay the start of projects,
      affect recruitment time, incur extra research costs and disadvantage PPI.
      Conclusion Buy-in to service user involvement in research studies could be
      improved by clarifying the requirements for NHS Trust approval and by simplifying
      the system for financial reimbursement to lay co-researchers. This would improve
      inclusivity and provide a smoother process for the research team and the co
      researchers.

PMID- 29062510
TI  - Going the extra mile - creating a co-operative model for supporting patient and
      public involvement in research.
AB  - PLAIN ENGLISH SUMMARY: In 2014, the Chief Medical Officer and Director General of
      Research and Development commissioned a review of patient and public involvement
      in the National Institute for Health Research. The report on this review,
      entitled 'Going the Extra Mile' was published in March, 2015. It described the
      bold goal of expecting all people using health and social care, and increasing
      numbers of the public, to be aware of and choosing to be involved in research.
      This requires more effort to build public awareness of research and better
      support for the public and researchers to do patient and public involvement in
      research. The author has created a new way of providing support for patient and
      public involvement based on co-operation between organisations. Termed 'share
      banking', this model pools limited resources across organisations to deliver a
      regional programme of support activities for patient and public involvement over
      the long term. This includes helping organisations to share and learn from each
      other to avoid 're-inventing wheels' (where separate organisations each develop
      the same thing from the beginning). The 'Going the Extra Mile' report recommends
      that local organisations should work together to deliver public involvement
      activities across a region. 'Share-banking' should help fulfil this
      recommendation. ABSTRACT: The 'Going the Extra Mile' final report opened with the
      ambition to increase the public's awareness, participation and involvement in
      research. It stated the need for public and researchers to be better supported to
      do public involvement. A new co-operative model, termed 'share-banking', has been
      developed whereby organisations pool limited resources to create and sustain
      support for patient and public involvement in research. This should fulfil the
      'Going the Extra Mile' report's recommendation to take a collaborative, cross
      organisational and regional approach to public involvement.

PMID- 29062512
TI  - Development of an online clinical trial recruitment portal for the NIHR mental
      health BRC.
AB  - PLAIN ENGLISH SUMMARY: In order to test whether or not new treatments for mental
      health disorders help patients get better according to clinician/patient selected
      criteria, it is often necessary to test them on patients under safe, carefully
      monitored conditions called clinical trials. It is necessary to find enough
      patients to take part in a clinical trial so that the results of the trial are
      reliable. The NIHR Mental Health BRC (here after abbreviated to BRC) is a centre
      for research in London which seeks to find out better ways to treat patients with
      mental health difficulties. The BRC has experienced problems trying to find
      sufficient numbers of patients to participate in its clinical trials as it
      appears that insufficient patients were being told by their doctor about
      opportunities to participate in clinical research. In order to help the BRC find
      enough patients to volunteer to take part in its clinical trials, the author (a
      patient representative) of this article and a clinical researcher in the nearby
      Institute of Psychiatry, Psychology and Neuroscience (IoPPN) decided to work
      together to try to find the best way to let patients know more about what
      clinical trials are, what it is like to take part in them and which clinical
      trials are seeking patients to take part. The author and researcher used a report
      by the Association of Medical Research Charities (AMRC) on patient difficulties
      in finding clinical trials to take part in, and the recommendations it made, to
      guide them in building a website to give such patients the information on
      clinical trials they wanted (including clinical trials run by the BRC). The
      author and researcher also asked patients, carers, staff at the IoPPN and BRC
      what they thought of the website and how to make it better. They used the ideas,
      suggestions and criticisms to improve the website. The author and researcher also
      asked mental health charities and research organisations if they would advertise
      the final version of this website on their own websites; many said yes, they
      would. The manager of the BRC on reviewing the website, agreed that a final
      version of the website with the NIHR Mental Health BRC logo would be paid for and
      will form part of a new main website for the BRC in early 2016. ABSTRACT: ?. ?:
      Public & patient recruitment to clinical trials is viewed as one of the main
      barriers to the implementation of clinical trials. This difficulty is often
      attributed to the working culture of the NHS, rapid turnover of staff and
      patients and poor-gatekeeping in referring patients to suitable clinical trials.
      In response to the recruitment difficulties experienced by the Psychosis Studies
      Clinical Academic Group at the NIHR Mental Health Biomedical Research Centre,
      Denmark Hill, London, a member of the Office of Psychosis Studies at King's
      College London and a member (the author) of the King's Clinical Trials Unit,
      King's College London developed an initiative to create an online clinical trial
      recruitment portal/information hub for the NIHR Mental Health BRC. The primary
      purpose of this initiative being to promote patient and public awareness of and
      interest in participating in clinical trials.

PMID- 29062513
TI  - Exploring the challenge of health research priority setting in partnership:
      reflections on the methodology used by the James Lind Alliance Pressure Ulcer
      Priority Setting Partnership.
AB  - PLAIN ENGLISH SUMMARY: The James Lind Alliance (JLA) brings patients, carers and
      clinicians together in Priority Setting Partnerships (PSPs) to identify and
      prioritise shared uncertainties about the effects of treatment. The JLA emerged
      from the evidence-informed healthcare movement to address a concern that the
      research being carried out on treatment effectiveness is not that of most
      importance to patients and health professionals. In the JLA PSPs, 'hard' evidence
      informed ideals meet 'soft' participatory practices. This article explores the
      challenges of putting co-production methods into practice by reflecting on the
      methods used by the JLA Pressure Ulcer PSP (JLAPUP). The JLA principles are
      transparency, inclusivity and avoiding waste in research. This means paying the
      same close critical attention to how PSPs are designed and run, as is desired in
      the health research which the JLA seeks to influence. JLAPUP showed that it was
      possible to work in partnership in a field where patients are often elderly,
      immobile, unrepresented and particularly unwell, many of whom are living with
      more than one long term condition. However, for those unfamiliar with it,
      'uncertainty' was a difficult term to get to grips with. Also, it was harder for
      some people than others to take part and to have their voices heard and
      understood. In keeping with other PSPs, JLAPUP found that the nature and quality
      of research into pressure ulcer prevention and treatment did not reflect the
      priorities of those who took part. ABSTRACT: ?. BACKGROUND: Studies identifying a
      mismatch between the priorities of academics and clinicians and those of people
      with direct experience of a health condition pose a challenge to the assumption
      that professional researchers can represent the interests of patients and the
      public in setting priorities for health research. The James Lind Alliance (JLA)
      brings patients, carers and clinicians together in Priority Setting Partnerships
      (PSPs) to identify and prioritise shared uncertainties about the effects of
      treatment. There is no formal evaluation yet to examine the different approaches
      used by individual PSPs and the impact these methods have on the quality of the
      partnership and subsequent outputs. There is no gold standard method for health
      research topic identification and priority setting and reporting on public
      involvement in this area is predominantly descriptive rather than evaluative.
      METHODS AND FINDINGS: The JLA Pressure Ulcer PSP (JLAPUP) was developed and
      worked between 2009 and 2013 to identify and prioritise the top 10
      'uncertainties', or 'unanswered questions', about the effects of pressure ulcer
      interventions. JLAPUP identified a mismatch between the nature and quality of
      RCTs in pressure ulcer prevention and treatment and the kind of research evidence
      desired by patients or service users, carers and health professionals. Results
      and methods have been reported fully elsewhere. The consultative and deliberative
      methods used to establish health research priorities in PSPs are fundamentally
      interpretive. PSPs are therefore an arena in which 'hard' evidence-informed
      ideals meet 'soft' participatory practices. This article provides an account of
      the challenges faced in one particular PSP. We explain the rationale for the
      approaches taken, difficulties faced and the limitations at each stage, because
      these aspects are particularly under-reported. The JLAPUP case is used to
      identify possible areas for evaluation and reporting across PSPs. CONCLUSION:
      Engaging people with very different health and life experiences in the
      complexities of health science based discussions of uncertainty is challenging.
      This is particularly the case when engaging groups routinely excluded from
      participating in health research, for example, older people with multiple
      comorbidities. The JLA principles of transparency, inclusivity and avoiding waste
      in research require paying close critical attention to PSP methodology, including
      full evaluation and reporting of PSP processes and outcomes. Assessing the impact
      of PSPs is contingent on the decision making processes of commissioners and
      funders.

PMID- 29062511
TI  - Engaging older adults in healthcare research and planning: a realist synthesis.
AB  - PLAIN ENGLISH SUMMARY: The importance of citizen involvement in healthcare
      research and planning has been widely recognized. There is however, a lack of
      understanding of how best to engage older adults, Canada's fastest growing
      segment of the population and biggest users of the healthcare system. We aimed to
      address this gap by developing an understanding of the engagement of older adults
      and their caregivers in healthcare research and planning. We conducted a review
      of available knowledge on engagement in healthcare research and planning with a
      focus on older adults and their caregivers. A five stage engagement framework
      emerged from this study that can be used to guide engagement efforts. We are
      continuing to collaborate with older adults and decision makers to develop and
      test strategies based on the presented framework. ABSTRACT: Background The
      importance of engaging the community in healthcare research and planning has been
      widely recognized. Currently however, there is a limited focus on older adults,
      Canada's fastest growing segment of the population and biggest users of the
      healthcare system. Objective This project aimed to develop an understanding of
      engagement of older adults and their caregivers in healthcare research and
      planning. Method A realist synthesis was conducted of the available knowledge on
      engagement in healthcare research and planning. The search methodology was
      informed by a framework for realist syntheses following five phases, including
      consultations with older adults. The synthesis included theoretical frameworks,
      and both peer-reviewed and grey literature. Results The search generated 15,683
      articles, with 562 focusing on healthcare research and planning. The review lead
      to the development of a framework to engage older adults and their caregivers in
      healthcare research and planning. The 5 stages environment, plan, establish,
      build, and transition are accompanied with example context, mechanism, and
      outcomes to guide the use of this framework. Conclusion We have identified a
      framework that promotes meaningful engagement of older adults and their
      caregivers. We are continuing to collaborate with our community partners to
      further develop and evaluate engagement strategies that align with the presented
      framework.

PMID- 29062514
TI  - Evaluating public involvement in research design and grant development: Using a
      qualitative document analysis method to analyse an award scheme for researchers.
AB  - PLAIN ENGLISH SUMMARY: The National Institute for Health Research (NIHR) Research
      Design Service (RDS) for Yorkshire and Humber has been running a public
      involvement funding scheme since 2008. This scheme awards researchers a small
      amount of money to help them get involvement from patients and/or the public.
      Involvement activities take place at the time when researchers are planning
      studies, and when they are completing application forms to request funding for a
      proposed research project. After the public involvement activities researchers
      are asked to write a report for the RDS describing what they did with the public
      involvement funding. This study analysed those reports using an approach which
      included members of a public involvement panel in the data analysis process. The
      aim of the work was to see what the views and experiences of researchers who
      received funding were, and what might be learned for the future of the scheme.
      Twenty five reports were analysed. Four main themes were identified, these
      described: the added value of public involvement; aspects to consider when
      planning and designing public involvement; different roles of public
      contributors; and aspects of valuing public member contributions. The group
      approach to analysis was successful in enabling involvement of a variety of
      individuals in the process. The findings of the study provide evidence of the
      value of public involvement during the development of applications for research
      funding. The results also indicate that researchers recognise the variety in
      potential roles for the public in research, and acknowledge how involvement adds
      value to studies. ABSTRACT: Background A regional Research Design Service, funded
      by the National Institute for Health Research, introduced a small grant in 2008,
      to support public involvement (often known as patient and public involvement
      [PPI]) activities during the development of applications for research funding.
      Successful applicants are requested to submit a report detailing how the grant
      money was used, including a description of the aims and outcomes of the public
      involvement activities. The purpose of this study was to analyse the content of
      these reports. We aimed to find out what researcher views and experiences of
      public involvement activities were, and what lessons might be learned. Methods We
      used an innovative method of data analysis, drawing on group participatory
      approaches, qualitative content analysis, and Framework Analysis to sort and
      label the content of the reports. We developed a framework of categories and sub
      categories (or themes and sub-themes) from this process. Results Twenty five
      documents were analysed. Four main themes were identified in the data: the added
      value of public involvement; planning and designing involvement; the role of
      public members; and valuing public member contributions. Within these themes, sub
      themes related to the timing of involvement (prior to the research study/intended
      during the research study), and also specific benefits of public involvement such
      as: validating ideas; ensuring appropriate outcomes; ensuring the acceptability
      of data collection methods/tools and advice regarding research processes. Other
      sub-themes related to: finding and approaching public members; timing of events;
      training/support; the format of sessions; setting up public involvement panels:
      use of public contributors in analysis and interpretation of data; and using
      public members to assist with dissemination and translation into practice.
      Conclusions The analysis of reports submitted by researchers following
      involvement events provides evidence of the value of public involvement during
      the development of applications for research funding, and details a method for
      involving members of the public in data analysis which could be of value to other
      researchers The findings of the analysis indicate recognition amongst researchers
      of the variety in potential roles for public members in research, and also an
      acknowledgement of how involvement adds value to studies.

PMID- 29062517
TI  - Consumer and community involvement in health and medical research: evaluation by
      online survey of Australian training workshops for researchers.
AB  - PLAIN ENGLISH SUMMARY: In Australia, since 2009, the Consumer and Community
      Involvement Program (formerly the Consumer and Community Participation Program)
      has developed and run workshops to help people working in health and medical
      research involve more consumers (patients) and community members (the public) in
      their research. In 2012, workshop attendees were invited to do an online survey
      to find out the effect, if any, that attending a workshop had on their awareness
      of and attitudes to consumer and community involvement. They were also asked
      about changes in their behaviour when it came to the involvement of consumers and
      the community in their work. The study found that, for people who answered the
      survey, more than double the number found consumer and community involvement very
      relevant after attending a workshop, compared with the number who thought that
      before attending one. Also, amongst those who answered the survey, 94 % thought
      that the workshop increased their understanding about involvement. ABSTRACT:
      Background There is limited evidence of the benefits of providing training
      workshops for researchers on how to involve consumers (patients) and the
      community (public) in health and medical research. Australian training workshops
      were evaluated to contribute to the evidence base. The key objective was to
      evaluate the impact of the workshops in increasing awareness of consumer and
      community involvement; changing attitudes to future implementation of involvement
      activities and influencing behaviour in the methods of involvement used. A
      secondary objective was to use a formal evaluation survey to build on the
      anecdotal feedback received from researchers about changes in awareness,
      attitudes and behaviours. Methods The study used a cross-sectional, online survey
      of researchers, students, clinicians, administrators and members of non
      government organisations who attended Consumer and Community Involvement Program
      training workshops between 2009 and 2012 to ascertain changes to awareness,
      attitudes and behaviours related to consumer and community involvement in health
      and medical research. Results Changes in awareness and attitudes were
      demonstrated by more than double the number of respondents finding involvement
      very relevant after attending a workshop compared with those who did so before
      attending; 94 % of respondents agreed that the workshops increased their
      understanding of how involvement can add value to research. Conclusions The
      training workshops raised awareness and increased relevance of consumer and
      community involvement among Australian researchers who attended a workshop and
      responded to the survey. The results of the survey are also suggestive that the
      training led to behaviour changes through increased consumer and community
      involvement.

PMID- 29062515
TI  - Prioritising target behaviours for research in diabetes: Using the nominal group
      technique to achieve consensus from key stakeholders.
AB  - PLAIN ENGLISH SUMMARY: The behaviour of people with diabetes (e.g. taking
      medication) and the behaviour of doctors and other healthcare professionals (e.g.
      checking patients' blood sugar) are important. Our research group wanted to
      select one patient behaviour and one healthcare professional behaviour as topics
      to research in Ireland. Patients and healthcare professionals are not usually
      asked to help decide on research topics. In this study, we wanted to bring
      together patients, healthcare professionals and policy makers to help us decide
      on the most important target behaviours for research in diabetes in Ireland. We
      worked with 24 participants, including people with diabetes, diabetes healthcare
      professionals and policy makers. First, participants suggested behaviours they
      thought were important to target for research in diabetes. Participants then
      attended a meeting and ranked which of the behaviours were the most important and
      discussed the results of the rankings as a group. We identified the most highly
      ranked patient and healthcare professional behaviours. The top ranked behaviour
      for people with Type 1 diabetes was to 'take insulin as required' and for people
      with Type 2 diabetes was to 'attend and engage with structured education
      programmes'. 'Engage in collaborative goal setting with patients' was the top
      ranked behaviour for healthcare professionals. Our study shows it is possible for
      researchers to work with people with diabetes, healthcare professionals and
      policy makers to decide on research topics. The top ranked behaviours will now be
      researched by our group in Ireland. ABSTRACT: Background Working with patients,
      healthcare providers, and policy makers to prioritise research topics may enhance
      the relevance of research and increase the likelihood of translating research
      findings into practice. The aim of the present study was to work with key
      stakeholders to identify, and achieve consensus on, the most important target
      behaviours for research in diabetes in Ireland. Methods Twenty-four participants,
      including people with diabetes, diabetes healthcare professionals and policy
      makers, took part in a nominal group technique consensus process. Through an
      online survey, participants generated lists of important target behaviours in
      three areas: managing Type 1 diabetes, managing Type 2 diabetes and preventing
      Type 2 diabetes. Participants then attended a research prioritisation meeting and
      ranked target behaviours in two rounds, with group discussion between ranking
      rounds. For each of the three key areas, the six top ranked behaviours relevant
      to people with diabetes and healthcare professionals were identified. Results In
      most cases, the most highly ranked behaviour was the same for Ranking 1 and
      Ranking 2 and consensus increased in relation to endorsement of top ranked
      behaviours. However, some behaviours did change position between rankings. The
      top behaviour relevant to people with Type 1 diabetes was 'taking insulin as
      required' and for people with Type 2 diabetes was 'attending and engaging with
      structured education programmes'. 'Engage in collaborative goal setting with
      patients' was the top ranked behaviour relevant to healthcare professionals for
      managing both Type 1 and Type 2 diabetes. For preventing Type 2 diabetes, 'engage
      in healthy behaviours as a family' was the highest ranked population behaviour
      and 'attend and engage with behaviour change training' was the highest ranked
      professional behaviour. Conclusions It is possible to work with a diverse group
      of stakeholders to inform the diabetes research agenda. The priorities identified
      were co-produced by key stakeholders, including patients, healthcare
      professionals and policy makers, and will inform the development of a programme
      of behavioural research in diabetes in Ireland. The study also provides a worked
      example of a research prioritisation process using the nominal group technique,
      and identified limitations, which may be useful for other researchers.

PMID- 29062516
TI  - A patient and public involvement (PPI) toolkit for meaningful and flexible
      involvement in clinical trials - a work in progress.
AB  - PLAIN LANGUAGE SUMMARY: Funders of research are increasingly requiring
      researchers to involve patients and the public in their research. Patient and
      public involvement (PPI) in research can potentially help researchers make sure
      that the design of their research is relevant, that it is participant friendly
      and ethically sound. Using and sharing PPI resources can benefit those involved
      in undertaking PPI, but existing PPI resources are not used consistently and this
      can lead to duplication of effort. This paper describes how we are developing a
      toolkit to support clinical trials teams in a clinical trials unit. The toolkit
      will provide a key 'off the shelf' resource to support trial teams with limited
      resources, in undertaking PPI. Key activities in further developing and
      maintaining the toolkit are to: ? listen to the views and experience of both
      research teams and patient and public contributors who use the tools; ? modify
      the tools based on our experience of using them; ? identify the need for future
      tools; ? update the toolkit based on any newly identified resources that come to
      light; ? raise awareness of the toolkit and ? work in collaboration with others
      to either develop or test out PPI resources in order to reduce duplication of
      work in PPI. ABSTRACT: Background Patient and public involvement (PPI) in
      research is increasingly a funder requirement due to the potential benefits in
      the design of relevant, participant friendly, ethically sound research. The use
      and sharing of resources can benefit PPI, but available resources are not
      consistently used leading to duplication of effort. This paper describes a
      developing toolkit to support clinical trials teams to undertake effective and
      meaningful PPI. Methods The first phase in developing the toolkit was to describe
      which PPI activities should be considered in the pathway of a clinical trial and
      at what stage these activities should take place. This pathway was informed
      through review of the type and timing of PPI activities within trials coordinated
      by the Clinical Trials Research Centre and previously described areas of
      potential PPI impact in trials. In the second phase, key websites around PPI and
      identification of resources opportunistically, e.g. in conversation with other
      trialists or social media, were used to identify resources. Tools were developed
      where gaps existed. Results A flowchart was developed describing PPI activities
      that should be considered in the clinical trial pathway and the point at which
      these activities should happen. Three toolkit domains were identified: planning
      PPI; supporting PPI; recording and evaluating PPI. Four main activities and
      corresponding tools were identified under the planning for PPI: developing a
      plan; identifying patient and public contributors; allocating appropriate costs;
      and managing expectations. In supporting PPI, tools were developed to review
      participant information sheets. These tools, which require a summary of potential
      trial participant characteristics and circumstances help to clarify requirements
      and expectations of PPI review. For recording and evaluating PPI, the planned PPI
      interventions should be monitored in terms of impact, and a tool to monitor
      public contributor experience is in development. Conclusions This toolkit
      provides a developing 'off the shelf' resource to support trial teams with
      limited resources in undertaking PPI. Key activities in further developing and
      maintaining the toolkit are to: listen to the views and experience of both
      research teams and public contributors using the tools, to identify the need for
      future tools, to modify tools based on experience of their use; to update the
      toolkit based on any newly identified resources that come to light; to raise
      awareness of the toolkit and to work in collaboration with others to both develop
      and test out PPI resources in order to reduce duplication of work in PPI.

PMID- 29062518
TI  - Developing resources to facilitate culturally-sensitive service planning and
      delivery - doing research inclusively with people with learning disabilities.
AB  - PLAIN ENGLISH SUMMARY: (Please see www.Toolsfortalking.co.uk for an easy read
      summary of the project.) The Tools for Talking are a set of resources that were
      developed through collaboration between Black, Asian and minority ethnic people
      with learning disabilities and researchers at the University of Birmingham. The
      resources were designed to be used by people with learning disabilities and
      service providers to facilitate culturally-sensitive communication and
      information sharing, service planning and delivery. They comprise illustrative
      videos and exploratory activities relating to five topics, namely, culture,
      activities, support from staff, important people, choices and independence. These
      topics emerged as important to people with learning disabilities during the
      'Access to Social Care-Learning Disabilities' (ASC-LD) study which involved
      interviews with 32 adults with learning disabilities from Black, Asian and
      minority ethnic communities. The results of the ASC-LD study were used to develop
      a set of draft resources which were then co-developed through collaboration with
      people with learning disabilities and service providers. A 'Partnership event'
      was convened to involve stakeholders in the development of the resources. This
      paper describes the refinement of these materials by people with learning
      disabilities from Black, Asian and minority ethnic backgrounds in cooperation
      with a range of other stakeholders. ABSTRACT: Background Black, Asian and
      minority ethnic people with learning disabilities face inequities in health and
      social care provision. Lower levels of service uptake and satisfaction with
      services have been reported, however, this is largely based on the views of
      carers. The 'Access to Social Care: Learning Disabilities (ASC-LD)' study sought
      to explore the views and experiences of social support services among adults with
      learning disabilities from Black, Asian and minority ethnic communities.
      Interviews with 32 Black, Asian and minority ethnic adults with learning
      disabilities were conducted to explore participants' cultural identities, their
      understanding and experience of 'support'. The views and experiences expressed in
      the ASC-LD study were used in the 'Tools for Talking project' to develop a suite
      of resources designed to facilitate culturally-sensitive communication and
      information-sharing, service planning and delivery through improved mutual
      understanding between providers and users of services. This paper describes the
      Tools for Talking project which sought to co-develop the resources through a
      partnership event. Methods An inclusive approach was adopted to address issues
      that are important to people with learning disabilities, to represent their views
      and experiences, and to involve Black, Asian and minority ethnic people with
      learning disabilities in the research process. Partnerships were developed with
      provider organisations and service users who were invited to a 'Partnership
      Event'. Collaborators at the partnership event were asked to comment on and
      evaluate draft resources which included a series of videos and activities to
      explore topics that emerged as important in the ASC-LD study. Their comments were
      collated and the tools developed as they suggested. Results Using the results
      from the ASC-LD study helped to ensure that the draft resources were relevant to
      service users, addressing topics that were important to them. The partnership
      event was an effective method to collaborate with a relatively large number of
      stakeholders. However, the event was resource intensive and required substantial
      planning to ensure active and meaningful participation. Considerations, such as
      inviting stakeholders, developing the programme and selecting a venue are
      discussed. Conclusions The partnership approach has led to the development of a
      set of five illustrative videos and accompanying activities that address issues
      that emerged from the collaborative process including: culture, activities,
      support from staff, important people, choices and independence. These resources
      are freely available at: www.Toolsfortalking.co.uk. They are designed to be used
      by users and providers of services, but may also be useful in other settings.

PMID- 29062519
TI  - Patient involvement in a qualitative meta-synthesis: lessons learnt.
AB  - PLAIN ENGLISH SUMMARY: Patients and researchers must work together to improve the
      relevance and quality of research. Qualitative systematic reviews synthesise
      findings from a range of published qualitative studies to identify common themes,
      and can make recommendations for practice or future research. The process of
      conducting a systemic review offers multiple opportunities for patient
      involvement.This paper explores the reflections of patient research partners
      involved in a qualitative systematic review. Patient partners were asked how
      their experience of the review process could be used to improve patient
      involvement in future qualitative systematic reviews. Following involvement in a
      systematic review an exploratory questionnaire was emailed to eight patient
      research partners. Open ended questions focussed on the training they had
      received, whether they had enjoyed taking part and how the process could be
      improved. Patients stated that they needed clear instructions and examples of how
      to take part in the systematic review. Face to face training was preferred, and
      it was important that patients were given enough time to complete the task. The
      study led to benefits for patients including gaining new skills and improved
      confidence. Each patient also wanted to know how their comments had influenced
      the paper and wanted feedback on whether they needed any further training.
      Through reflection with patient partners, recommendations for the involvement of
      patients in qualitative systematic reviews were developed to allow researchers to
      successfully involve patients in the review process. ABSTRACT: Background Patient
      involvement in systematic reviews is seen as good practice, yet there is a lack
      of accessible standardised training for those involved. The aim of this paper is
      to inform the evidence base on effective ways of involving patients in a
      qualitative meta-synthesis. This process is evaluated and reflected by patient
      research partners (PRPs) who provided accounts of their experience. Methods An
      open ended questionnaire was emailed to eight PRPs who had participated in the
      analysis of a qualitative meta-synthesis. Questions focussed on the training they
      received, their experience of coding data and identifying themes, whether they
      enjoyed taking part in the project and how the process could be improved. Results
      Our findings point to the importance of detailed training for PRPs, using plain
      English and clear examples of analysis techniques to improve confidence in
      engaging with meta-synthesis methods. Face to face training was preferred in
      order to discuss a PRP's understanding of the task ahead. Time is an important
      consideration as PRPs often complete this work on top of their daily commitments
      and need the time and on-going support to be able to immerse themselves in the
      data. A focus group was a useful way to discuss the themes but it is important
      that PRPs understand how their comments have influenced the paper. PRPs reported
      benefits that included building new skills, improving confidence and gaining
      knowledge. They also asked for feedback on their contribution and any further
      training needs. All PRPs said they would take part in a meta-synthesis in the
      future as long as these considerations were addressed. Conclusion The
      recommendations for practice identified in this paper, and guidelines for
      training, can assist researchers in collaborating with PRPs when developing and
      conducting a qualitative meta-synthesis.

PMID- 29062520
TI  - Patient and public involvement in patient safety research: a workshop to review
      patient information, minimise psychological risk and inform research.
AB  - PLAIN ENGLISH SUMMARY: Patient safety is a growing research area. However,
      although patients and the public are increasingly involved in clinical research,
      there is little guidance on how best to involve patients in patient safety
      research. Here we focus on how patients can contribute to the design of patient
      safety research. We conducted a workshop with patients as part of a project
      exploring errors and safety in the delivery of intravenous medication (medication
      given via a vein). The workshop was designed to explore how best to engage with
      hospital inpatients about these issues, to generate research topics, and to
      inform researchers about patients' experiences. Nine patients participated, each
      of whom had previously received intravenous medication. Participants advised
      against using terms such as 'error'; they also advocated caution when using terms
      such as 'safety' when describing the study to patients as this may worry some who
      had not thought about these issues before. We received thorough and useful
      feedback on our patient information sheets to ensure they were clear and
      understandable to patients. Patients also shared rich experiences with us about
      their treatment, which emphasised the need to extend our research focus to
      include a wider range of factors affecting quality and safety. ABSTRACT:
      Background Patient safety has attracted increasing attention in recent years.
      This paper explores patients' contributions to informing patient safety research
      at an early stage, within a project on intravenous infusion errors. Currently,
      there is little or no guidance on how best to involve patients and the wider
      public in shaping patient safety research, and indeed, whether such efforts are
      worthwhile. Method We ran a 3-hour workshop involving nine patients with
      experience of intravenous therapy in the hospital setting. The first part
      explored patients' experiences of intravenous therapy. We derived research
      questions from the resulting discussion through qualitative analysis. In the
      second part, patients were asked for feedback on patient information sheets
      considering both content and clarity, and on two potential approaches to framing
      our patient information: one that focused on research on safety and error, the
      other on quality improvement. Results The workshop led to a thorough review of
      how we should engage with patients. Importantly, there was a clear steer away
      from terms such as 'error' and 'safety' that could worry patients. The
      experiences that patients revealed were also richer than we had anticipated,
      revealing different conceptions of how patients related to their treatment and
      care, their role in safety and use of medical devices, the different levels of
      information they preferred, and broader factors impacting perceptions of their
      care. Conclusion Involving patients at an early stage in patient safety research
      can be of great value. Our workshop highlighted sensitivities around potentially
      worrying patients about risks that they might not have considered previously, and
      how to address these. Patient representatives also emphasised a need to expand
      the focus of patient safety research beyond clinicians and error, to include
      factors affecting perceptions of quality and safety for patients more broadly.

PMID- 29062521
TI  - Patients' perspectives can be integrated in health technology assessments: an
      exploratory analysis of CADTH Common Drug Review.
AB  - PLAIN LANGUAGE SUMMARY: In Canada, the CADTH Common Drug Review helps ensure that
      scarce health care resources are used to fund the most effective drugs.
      Clinicians, researchers, payers, and patients all have important, but potentially
      different, ideas on what should be considered, to determine a drug's value. Since
      2010, CADTH has invited patient groups to contribute their perspectives to the
      Common Drug Review. We explored whether, and how, insights offered by patient
      groups are integrated into assessment reports and Recommendations by the CADTH
      Canadian Drug Expert Committee. After examining 30 completed drug assessments, we
      found that:Patient insights are used by CADTH reviewers to frame an assessment
      and are used by the expert committee to interpret the evidence.Drug trials do not
      always measure outcomes that patients consider important.Survival, symptom
      relief, the process of recovery, and maintaining health are all important aspects
      to consider when determining value during health technology assessments.
      ABSTRACT: Background Since 2010, Canadian patient groups have contributed to the
      CADTH Common Drug Review (CDR). CADTH conducts health technology assessments of
      new drugs to support publicly funded drug plans' reimbursement decisions. We
      explored whether, and how, patient insights were integrated into assessment
      reports and Recommendations by the CADTH Canadian Drug Expert Committee (CDEC).
      Methods We descriptively analyzed 30 consecutive assessments. One researcher
      identified a set of issues, insights, and desired treatment outcomes provided by
      patient groups for each included drug assessment. We tracked the presence of each
      identified patient insight in the relevant assessment protocol, in clinical
      trials as reported in the assessment, and in the CDEC Recommendations.
      Additionally, patient insights were categorized by topic and grouped into a three
      tier framework to explore the observed juxtaposition between immediate treatment
      outcomes as seen in clinical trials and the insights from patients living with a
      chronic condition. Results In 30 drug assessments, 119 patient insights were
      identified. Of these insights, 89 were included in assessment protocols; 61 in
      reported clinical trial data; and 67 insights were reflected upon within the CDEC
      Recommendations. Patient insights within the first framework tier (health status
      achieved) were frequently included in all aspects of CDR assessments. Within the
      second tier (progress of recovery), although two-thirds of patient insights were
      included in protocols, only one-third was reflected in reported trial data or in
      CDEC Recommendations. Insights within the third tier, which address the long-term
      consequences of illness and treatment, were even less frequently addressed in all
      aspects of CDR assessments. Conclusions Patients' perspectives need not be
      "considered" in isolation. Patient insights are used by CADTH reviewers to frame
      an assessment and used by CDEC to interpret the evidence. As health technology
      assessments should address the indirect and unintended consequences of a
      technology, as well as its direct and intended effects, drug assessments should
      consider the progress of recovery and sustainability of health, in addition to
      survival and immediate health achieved.

PMID- 29062522
TI  - Study protocol: Determining what young people with rheumatic disease consider
      important to research (the Young People's Opinions Underpinning Rheumatology
      Research - YOURR project).
AB  - PLAIN ENGLISH SUMMARY: Involving young people in research about their health is
      increasingly recognized as being important to make sure that research is focused
      more on the needs of young people. However, at present, ideas about what should
      be researched and found out mainly come from researchers and health professionals
      like doctors and nurses rather than young people. Therefore, in the past, young
      people's ideas about what should be researched in terms of rheumatic problems
      have not been explored. In this study, we will talk with groups of young people
      with rheumatic problems across the UK to explore what they think research into
      their health should focus on. We will also discuss with young people, if and how,
      they would like to be involved in shaping research into rheumatic problems. The
      findings from this work will help make sure that the views of young people with
      rheumatic problems influence the work of a group of researchers and health
      professionals who concentrate on rheumatology research. This group is called the
      Barbara Ansell National Network for Adolescent Rheumatology (BANNAR). A national
      young person's advisory group will be set up to make sure that the beliefs and
      ideas of young people with rheumatic disease inform the work of the BANNAR.
      ABSTRACT: Background The involvement of people of all ages (including young
      people) in health-related research is now widely advocated but research
      priorities are still largely driven by professional agendas, with evidence from
      the adult literature reporting a mismatch between researcher and patient
      generated lists of research topics. To date, there have been no studies exploring
      the research priorities of young people with long term conditions including
      rheumatic disease. In this study, we will explore young people's beliefs about
      their research priorities for rheumatic conditions and whether and how young
      people would like to become involved in the research process. Methods/Design We
      will hold up to 16 focus group discussions with young people (11-24 years) across
      England, Northern Ireland, Scotland and Wales. Two age groups will be recruited
      to the study, 11-15 year olds to represent early and mid-adolescence and 16-24
      year olds to reflect late adolescence and emerging adulthood. Focus groups will
      be as interactive and engaging as possible, using a mixture of statement sorting
      and a research prioritization exercise to stimulate the discussion. Young people
      will be recruited via members of the Barbara Ansell National Network for
      Adolescent Rheumatology (BANNAR) and relevant national charities. Focus groups
      will be audiotaped and transcribed for analysis. Discussion This project will
      help ensure full representation from young people with rheumatic diseases in the
      development of a research strategy for BANNAR and will ultimately inform a young
      person's led involvement strategy to facilitate the future ethical and meaningful
      involvement of young people in BANNAR members' future research programmes. In
      addition, a national young persons' advisory group will be established, the
      constitution and format of which will be determined by the young people
      themselves.

PMID- 29062524
TI  - Development of a decision guide to support the elderly in decision making about
      location of care: an iterative, user-centered design.
AB  - PLAIN ENGLISH SUMMARY: For the elderly to get the care and services they need,
      they may need to make the difficult decision about staying in their home or
      moving to another home. Many other people may be involved in their care too
      (friends, family and healthcare providers), and can support them in making the
      decision. We asked informal caregivers of elderly people to help us develop a
      decision guide to support them and their loved ones in making this decision. This
      guide will be used by health providers in home care who are trained to help
      people make decisions. The guide is in French and English. To design and test
      this decision guide we involved elderly people, their caregivers and health
      administrators. We first asked them what they needed for making the decision, and
      then designed a first version of the guide. Then we asked them to look at it and
      give feedback, which was used to make the final version. We then used scientific
      criteria to check its content and the language used. The final decision guide was
      acceptable to the caregivers, their elderly loved ones, and the health
      administrators. The guide is currently being evaluated in a large research
      project with home care teams in the province of Quebec. ABSTRACT: Background As
      they grow older, many elderly people are faced with the difficult and preference
      sensitive decision about staying in their home or moving to a residence better
      adapted to their evolving care needs. We aimed to develop an English and French
      decision aid (DA) for elderly people facing this decision, and to involve end
      users in all phases of the development process. Methods A three-cycle design with
      involvement of end-users in Quebec. End-users were elderly people (n = 4)
      caregivers of the elderly (n = 5), health administrators involved in home-care
      service delivery or policy (n = 6) and an interprofessional research team (n =
      19). Cycle 1: Decisional needs assessment and development of the first prototype
      based on existing tools and input from end-users; overview of reviews examining
      the impact of location of care on elderly people's health outcomes. Cycle 2:
      Usability testing with end-users, adaptation of prototype. Cycle 3: Refinement of
      the prototype with a linguist, graphic designer and end-users. The final
      prototype underwent readability testing and an International Patient Decision
      Aids (IPDAS) criteria compatibility assessment to verify minimal requirements for
      decision aids and was tested for usability by the elderly. ResultsCycle 1: We
      used the Ottawa Personal Decision Guide to design a first prototype. As the
      overview of reviews did not find definitive evidence regarding optimal locations
      of care for elderly people, we were not able to add evidence-based advantages and
      disadvantages to the guide. Cycle 2: Overall, the caregivers and health
      administrators who evaluated the prototype (n = 10) were positive. In response to
      their suggestions, we deleted some elements (overview of pros, cons, and
      consequences of the options) that were necessary to qualify the tool as a DA and
      renamed it a "decision guide". Cycle 3: We developed French and English versions
      of the guide, readable at a primary school level. The elderly judged the guide as
      acceptable. Conclusion We developed a decision guide to support elderly people
      and their caregivers in decision making about location of care. This paper is one
      of few to report on a fully collaborative approach to decision guide development
      that involves end-users at every stage (caregivers and health administrators
      early on, the frail elderly in the final stages). The guide is currently being
      evaluated in a cluster randomized trial. Trial registration: NCT02244359.

PMID- 29062525
TI  - Keeping it credible in cohort multiple Randomised Controlled Trials: the
      Community Ageing Research 75+ (CARE 75+) study model of patient and public
      involvement and engagement.
AB  - PLAIN ENGLISH SUMMARY: There are well documented benefits to involving patients
      and the public in research. However, there is little research published about
      their involvement in large complex studies such as cohort multiple Randomised
      Controlled Trials (cmRCTs). The cmRCT method establishes a group of participants,
      with a common characteristic (e.g. older people) who will be followed over a
      number of years. Other (sub) studies can also recruit from this pool of people.
      This method offers researchers many advantages, including being able to recruit
      from more hard to reach groups. However, cmRCTs also have features which can make
      it more complicated to involve patients and the public. For example more than one
      study may take place at the same time; studies may be spread out over a large
      geographical area and they may include a wide range of topics. In spite of these
      difficulties we have developed a way of working with patients, the public and
      researchers that provides stability over time but allows flexibility along the
      way. Our model of working has saved us time and money; helped us to recruit more
      widely, and enabled us to focus our research in areas that are important to older
      people with frailty. ABSTRACT: Background There is increasing guidance on how to
      make the most of the rich seam of data provided by large cohort studies, and
      growing recognition of the benefits of cohort multiple Randomised Controlled
      Trials (cmRCT) in health research. In contrast, there is a lack of discussion
      about patient and public involvement and engagement (PPIE) in these large and
      complex research infrastructures. Our aim was to create a structure to enable
      meaningful, sustainable public involvement within the cmRCT framework. We have
      established a core reference group of four key individuals with extensive links
      to other relevant local community structures and individuals. Results Using the
      CARE 75+ model we have engaged with a wide variety of patients and the public in
      a relatively short space of time. Activities have included scrutiny of protocols
      and assessment tools, and process evaluations; resulting in system efficiencies,
      increased recruitment and a more focused research agenda. Conclusions There is a
      need for strong public oversight and flexible models of PPIE in cmRCTs. The model
      of PPIE developed in the Community Ageing Research 75+ study presents one
      potential way to foster expertise and enable diversity.

PMID- 29062526
TI  - Learning to work together - lessons from a reflective analysis of a research
      project on public involvement.
AB  - PLAIN ENGLISH SUMMARY: Patient and public involvement (PPI) in research is very
      important, and funders and the NHS all expect this to happen. What this means in
      practice, and how to make it really successful, is therefore an important
      research question. This article analyses the experience of a research team using
      PPI, and makes recommendations on strengthening PPI in research. There were
      different PPI roles in our study - some people were part of the research team:
      some were on the advisory group; and there were patient groups who gave specific
      feedback on how to make research work better for their needs. We used minutes,
      other written documents, and structured individual and group reflections to learn
      from our own experiences over time. The main findings were:- for researchers and
      those in a PPI role to work in partnership, project structures must allow
      flexibility and responsiveness to different people's ideas and needs; a named
      link person can ensure support; PPI representatives need to feel fully included
      in the research; make clear what is expected for all roles; and ensure enough
      time and funding to allow meaningful involvement. Some roles brought more demands
      but also more rewards than others - highlighting that it is important that people
      giving up their time to help with research experience gains from doing so. Those
      contributing to PPI on a regular basis may want to learn new skills, rather than
      always doing the same things. Researchers and the public need to find ways to
      develop roles in PPI over time. We also found that, even for a team with
      expertise in PPI, there was a need both for understanding of different ways to
      contribute, and an evolving 'normalisation' of new ways of working together over
      time, which both enriched the process and the outputs. ABSTRACT: Background
      Patient and public involvement (PPI) is now an expectation of research funders,
      in the UK, but there is relatively little published literature on what this means
      in practice - nor is there much evaluative research about implementation and
      outputs. Policy literature endorses the need to include PPI representation at all
      stages of planning, performing and research dissemination, and recommends
      resource allocation to these roles; but details of how to make such inputs
      effective in practice are less common. While literature on power and
      participation informs the debate, there are relatively few published case studies
      of how this can play out through the lived experience of PPI in research; early
      findings highlight key issues around access to knowledge, resources, and
      interpersonal respect. This article describes the findings of a case study of PPI
      within a study about PPI in research. Methods The aim of the study was to look at
      how the PPI representatives' inputs had developed over time, key challenges and
      changes, and lessons learned. We used realist evaluation and normalisation
      process theory to frame and analyse the data, which was drawn from project
      documentation, minutes of meetings and workshops, field notes and observations
      made by PPI representatives and researchers; documented feedback after meetings
      and activities; and the structured feedback from two formal reflective meetings.
      Results Key findings included the need for named contacts who support, integrate
      and work with PPI contributors and researchers, to ensure partnership working is
      encouraged and supported to be as effective as possible. A structure for
      partnership working enabled this to be enacted systematically across all
      settings. Some individual tensions were nonetheless identified around different
      roles, with possible implications for clarifying expectations and deepening
      understandings of the different types of PPI contribution and of their
      importance. Even in a team with research expertise in PPI, the data showed that
      there were different phases and challenges to 'normalising' the PPI input to the
      project. Mutual commitment and flexibility, embedded through relationships across
      the team, led to inclusion and collaboration. Conclusion Work on developing
      relationships and teambuilding are as important for enabling partnership between
      PPI representatives and researchers as more practical components such as funding
      and information sharing. Early explicit exploration of the different roles and
      their contributions may assist effective participation and satisfaction.

PMID- 29062523
TI  - Giving voice to older adults living with frailty and their family caregivers:
      engagement of older adults living with frailty in research, health care decision
      making, and in health policy.
AB  - PLAIN ENGLISH SUMMARY: The paper discusses engaging older adults living with
      frailty and their family caregivers. Frailty is a state that puts an individual
      at a higher risk for poor health outcomes and death. Understanding whether a
      person is frail is important because treatment and health care choices for
      someone living with frailty may be different from someone who is not (i.e., who
      is fit). In this review, we discuss strategies and hurdles for engaging older
      adults living with frailty across three settings: research, health and social
      care, and policy. We developed this review using published literature, expert
      opinion, and stakeholder input (including citizens). Engaging frail older
      individuals will be challenging because of their vulnerable health state - but it
      can be done. Points of consideration specific to engaging this vulnerable
      population include:In any setting, family caregivers (defined to include family,
      friends, and other social support systems) play an important role in engaging and
      empowering older adults living with frailtyEngagement opportunities need to be
      flexible (e.g., location, time, type)Incentivizing engagement for researchers and
      citizens (financial and otherwise) may be necessaryThe education and training of
      citizens, health and social care providers, and researchers on engagement
      practicesPatient-centered care approaches should consider the specific needs of
      individuals living with frailty including end-of-life care and advanced care
      planningInfluencing policy can occur in many ways including participating at
      institutional, regional, provincial or national committees that relate to health
      and social care. ABSTRACT: Older adults are the fastest growing segment of
      Canada's population resulting in an increased number of individuals living with
      frailty. Although aging and frailty are not synonymous the proportion of those
      who are frail increases with age. Frailty is not defined by a single condition,
      but rather a health state characterized by an increased risk of physical, mental,
      or social decline, deterioration of health status, and death. Recognizing frailty
      is important because earlier detection allows for program implementation focused
      on prevention and management to reduce future hospitalization, improve outcomes,
      and enhance vitality and quality of life. Even though older adults living with
      frailty are significant users of health care resources, their input is under
      represented in research, health care decision making, and health policy
      formulation. As such, engaging older adults living with frailty and their family
      caregivers is not only an ethical imperative, but their input is particularly
      important as health and social care systems evolve from single-illness focused to
      those that account for the complex and chronic needs that accompany frailty. In
      this review, we summarize existing literature on engaging older adults living
      with frailty and their family caregivers across three settings: research, health
      and social care, and policy. We discuss strategies and barriers to engagement,
      and ethical and cultural factors and implications. Although this review is mainly
      focused on Canada it is likely to be broadly applicable to many of the health
      systems in the developed world where aging and frailty pose important challenges.

PMID- 29062527
TI  - Patient advocate perspectives on involvement in HTA: an international snapshot.
AB  - PLAIN ENGLISH SUMMARY: A number of health technology assessment (HTA)
      organisations have developed processes to engage patients in the assessment of
      new health technologies such as pharmaceuticals, diagnostic tests, devices or
      medical procedures. Typically, this involves the HTA agency providing an
      opportunity for patient advocates and their patient organisations (support groups
      for patients with a specific disease or condition) to provide submissions
      detailing experiences with the disease and the health technology that is being
      assessed. While some literature exists about how HTA agencies view the engagement
      of patients in the HTA process, it is not yet clear how the patient advocates and
      patient organisations themselves view this engagement. To answer this question,
      we surveyed the views of patient advocates who were members of patient
      organisations known to be engaged in the process of HTA or evidence-based
      practice. Snowballing - that is, passing on the survey invitation from
      individuals invited to take part in the survey to other individuals - occurred in
      one of the countries. The responses in this country provided a very useful
      comparison between the views of people who were appointed as the 'patient
      representatives' on an HTA committee with those who contributed input as part of
      the general patient organisation engagement process. Our findings identify gaps
      in understanding of the purpose of patient involvement and whether patient
      organisations felt their input made a difference, the information and support
      provided, and if and how feedback is given to the patient organisations. Our work
      can help inform further research as well as continuing improvements in HTA
      patient engagement processes. ABSTRACT: Background Patient involvement in health
      technology assessment (HTA) processes is becoming more frequent. However, it is
      not clear how patient advocates and their disease-based patient organisations
      that are involved in HTA view their involvement. We report on the results of an
      international survey of patient advocates and members of patient organisations
      about their experiences and perceptions of that involvement. Methods A 16
      question survey was sent out to patient advocates and members of patient groups
      known to be involved in HTA processes or evidence-based practice. The survey
      consisted of open-ended questions focusing on respondent characteristics, stage
      and nature of involvement, support from HTA agencies for involvement, purpose of
      involvement, feedback on involvement, and whether the respondents felt that their
      input made a difference. Results Of 16 individuals who received the survey, 15
      responded. Three, from Italy, Israel and Japan, were not involved in HTA in their
      country. Respondents from the following countries reported involvement in HTA
      processes: Canada, England, Scotland, and Wales, The Netherlands, Australia,
      Taiwan. The respondents indicated that HTA agencies reach out to them either
      actively or passively, and that their involvement is often at the appraisal stage
      of HTA. Typically, they reported involvement as either participants in committees
      or providers of submissions to HTA agencies. A wide range of approaches to
      supporting patient involvement by the HTA agencies was identified by respondents 
      including personal and telephone support, online resources, training and
      provision of information - but the level and type of support reported was uneven
      across jurisdictions. Not all respondents were clear on the purpose of their
      involvement in HTA, although some were able to cite specific examples of how
      their input made a difference; members of an HTA decision-making committee
      appeared to have a better understanding and were able to give examples. Feedback
      from HTA agencies to the patient groups on their submissions is often not
      provided. Conclusions Although considerable progress has been made in terms of
      engaging patients and patient groups in HTA, gaps remain in how involvement is
      supported, including facilitating involvement, clarity on roles, two-way flow of
      information, and methods for enhancing communication between patient
      organisations and HTA agencies.

PMID- 29062528
TI  - Strengthening international patient advocacy perspectives on patient involvement
      in HTA within the HTAi Patient and Citizen Involvement Interest Group -
      Commentary.
AB  - PLAIN LANGUAGE SUMMARY: Health Technology Assessment (HTA) is an evidence-based
      decision-making process, focusing on evaluating health technologies for funding
      within a healthcare system. 'Health technologies' include medications, medical
      devices, diagnostics, medical procedures and services. Health Technology
      Assessment international (HTAi) is a global society for those who produce, use,
      participate in, or encounter HTA. The HTAi Secretariat supports special interest
      groups within HTAi. One such special interest group, the Patient and Citizen
      Involvement in HTA Interest Group (PCIG), focuses on strengthening patient
      involvement in HTA. PCIG's members are from HTA agencies, research, industry, and
      patient organisations. We describe the steps PCIG has taken to form an
      international panel of patient advocates (the Patient Panel) as an autonomous
      group within its governance structure that reports directly to the PCIG Steering
      Committee. The Patient Panel was established in order to strengthen meaningful
      patient involvement in HTA by working co-productively with other PCIG members to
      develop resources accessible to patient organisations. Patient advocates known to
      be active within HTA in their own countries were invited to form the inaugural
      group, with one person appointed to chair the group for the first year.
      Documentation had been prepared to inform potential members and set out potential
      roles as seen by the Steering Committee. The appointed Patient Panel is defining
      its own terms of reference, goals and objectives. The Panel Chair is a member of
      the PCIG Steering Committee, and is mentored by the retiring PCIG chair. A
      registry of activities is part of monitoring and evaluation. ABSTRACT: Background
      Health Technology Assessment (HTA) is an evidence-based decision-making process,
      focusing on evaluating health technologies for funding within a healthcare system
      or medical insurance system. 'Health technologies' are understood broadly, and
      include medications, medical devices, diagnostics, medical procedures and
      services. Health Technology Assessment international (HTAi) is a global society
      for those who produce, use, participate in, or encounter HTA. The HTAi
      Secretariat supports special interest groups within HTAi, including the Patient
      and Citizen Involvement in HTA Interest Group (PCIG), which focuses on
      strengthening patient involvement in HTA. PCIG's members come from HTA agencies,
      research, industry, and patient organisations. Main body We describe the steps
      the PCIG has taken to form an international panel of patient advocates as an
      autonomous group within its governance structure, reporting directly to the PCIG
      Steering Committee. Patient advocates known to be active within HTA in their own
      countries were invited to form the inaugural group. One person was invited to
      chair the Panel for the first year of its operation, based on the candidate's
      experience of working across diseases and countries, and being new to HTAi.
      Documentation was prepared to inform potential members of the Panel and set out
      potential roles as seen by the Steering Committee. The Panel came into being in
      March 2016 and is now setting out its own working principles, goals and
      objectives. The Panel Chair is a member of the PCIG Steering Committee, and is
      mentored by the previous PCIG chair. A registry of activities has been set up as
      part of monitoring and evaluation. The Patient Panel is intended to provide a
      focus within the PCIG for patient advocates to work among themselves and co
      productively through the PCIG Working Groups to develop mutual understanding and
      strengthen meaningful patient involvement in HTA internationally. Patient
      advocates can benefit from a clear understanding the evidence requirements within
      HTA and how information can be effectively presented by patient groups to
      decision-making bodies. Conclusion The HTAi Patient and Citizen Involvement
      Interest Group has set up a Patient Panel consisting of patient advocates. The
      intent is to work co-productively to advance patient involvement in HTA.

PMID- 29062529
TI  - Priority setting in research: user led mental health research.
AB  - PLAIN ENGLISH SUMMARY: Involving people in health research is increasingly
      recognised as being important to make sure that research is focused more on the
      needs of people who use health services. At present, ideas about what should be
      researched most often comes from researchers and/or health professionals like
      doctors and nurses rather than people with a lived experience of mental illness.
      In this study, we will talk with this group of people from across Wales to
      explore what they think research into their health services should focus on. The
      findings from this work will help to influence the work of the National Centre
      for Mental Health Research Partnership Group; as well as' researchers and health
      professionals and others who concentrate on mental health research. The Research
      group is a partnership between people with a lived experience of mental ill
      health and professionals with an interest in mental ill health. The group plan to
      take forward the ideas that came from this research and some of the ideas have
      already been used to increase funding in the area of mental health research.
      ABSTRACT: Background This paper is the result of continued collaboration between
      members of the Service User and Carer Research Partnership, based in Wales and
      supported by the National Centre for Mental Health, Health and Care Research
      Wales, and Hafal. The aim of this study was to explore the research priorities of
      people with experience of mental health services which include people with a
      lived experience of mental ill health, their carers, and professionals. Method A
      nominal group technique was used to gather data. A one-day workshop 'Getting
      Involved in Research: Priority Setting' was held to gather the ideas and
      suggestions for research priorities from people who have experience of mental
      health services. Results Twenty-five participants attended the workshop. 5 were
      mental health professionals, 20 had a lived experience of mental ill health, (of
      which 3 were also carers). 11 were male and 14 were female. 120 research ideas
      were generated across 6 'Ideas Generating Workstations'. Participants took part
      in a 3 stage vote to narrow down the ideas to 2 main research priorities.
      Conclusion The two main research priority areas that were identified:'Developing
      the knowledge of mental health issues amongst school-aged children' as a vehicle
      to overcome stigma and discrimination, and to support young people to manage
      their own mental health.'Developing education as a tool for recovery', for
      example by peer support. In addition, participants engaged in a notable
      discussion over the research priority: 'How are carers supported during the
      recovery of the person for whom they care?'

PMID- 29062530
TI  - "Hitting the spot": Developing individuals with lived-experience of health and
      social care as facilitators to deliver a course to enhance public involvement in
      research - a Welsh perspective.
AB  - PLAIN ENGLISH SUMMARY: Public involvement in research has become an important and
      integral part of the research process in health and social care, from the early
      stages of research prioritisation and development to the later stages of research
      conduct and dissemination. Learning and development opportunities, including
      training, can assist the public and researchers in working together in the
      research process, and a training schedule exists in Wales for this purpose. One
      of the key components of this training schedule in Wales is the course Involving
      the Public in the Design and Conduct of Research: Building Research Partnerships.
      Building on the existing successes of this UK-wide course, first developed by
      Macmillan Cancer Support, a project was established between Health and Care
      Research Wales and Macmillan Cancer Support to develop three members of the
      Involving People Network into trained facilitators. Once trained, the aim was for
      the three facilitators to deliver the course in Wales. Macmillan Cancer Support
      and Health and Care Research Wales selected, through a competitive process, three
      members of the Involving People Network to use their lived experience of
      Involvement in research projects, as well as any lived experience of a physical
      or mental health condition or illness, to become facilitators of the course in
      the unique context of public involvement in research in Wales. Through this
      process many benefits were realised, including developing the course content and
      its delivery in Wales, as well as building the skills and confidence of the
      individuals themselves as facilitators. This has contributed to a continuing
      commitment to the sustainable delivery of the Involving the Public in the Design
      and Conduct of Research: Building Research Partnerships course in Wales and a
      combined approach to addressing any challenges and obstacles which presented.
      ABSTRACT: Health and Care Research Wales has a strategic aim to Ensure public
      involvement and engagement is central to what we do and visible in all elements
      of it. As part of the ongoing development of the Health and Care Research Wales
      Training Programme a project was initiated to develop members of the public as
      facilitators to deliver a public involvement in research course. The project was
      undertaken in collaboration with Macmillan Cancer Support and was advertised via
      the Involving People Network in Wales. Three trainee facilitators were recruited,
      from 14 people that applied, to deliver a public involvement in research training
      course, the Building Research Partnerships course, as it was known then,
      originally developed for and by Macmillan Cancer Support. As members of the
      Involving People Network, the trainees were given training, mentorship, financial
      and administrative support to develop their role as facilitators over a two year
      period. This has been reciprocated with incredible commitment, ongoing course
      delivery in Wales, excellent course evaluations, course review and involvement in
      future planning. Through this project several benefits were realised, including
      developing the course content and its delivery and building the skills and
      confidence of the individual facilitators themselves. Additionally, and
      importantly, the project team found that patients and members of the public who
      are given appropriate training and support can greatly enhance a research
      training programme and act as highly effective ambassadors to further the cause
      of public involvement in research.

PMID- 29062531
TI  - A framework for public involvement at the design stage of NHS health and social
      care research: time to develop ethically conscious standards.
AB  - PLAIN ENGLISH SUMMARY: Researchers who conduct studies in health and social care
      are encouraged to involve the public as early as possible in the process of
      designing their studies. Before their studies are allowed to start researchers
      must seek approval from a Research Ethics Committee, which will assess whether
      the study is going to be safe and ethical for patients or healthy volunteers to
      take part in. The process of ethical review does not consider how researchers
      work with patients and the public early on to design their studies. Furthermore,
      there is no requirement for researchers to seek ethical approval for public
      involvement. However, in our work advising researchers about public involvement
      we have found that the ways in which researchers involve the public in the design
      of their studies are sometimes unintentionally unethical, and this is the focus
      of our paper. We have observed ten areas where ethical issues may arise because
      of the actions researchers may or may not take and which might consequently have
      a negative impact. Therefore, we have used these observations to develop a
      "framework" to help researchers and the public work together at the early design
      stage in ways that are ethical. Our intention for the framework is to help
      researchers be mindful of these ten areas and how easily ethical issues can
      arise. The framework suggests some ways to overcome the potential issues in each
      of the ten areas. The ten areas are: 1) Allocating sufficient time for public
      involvement; 2) Avoiding tokenism; 3) Registering research design stage public
      involvement work with NHS Research & Development Trust Office at earliest
      opportunity; 4) Communicating clearly from the outset; 5) Entitling public
      contributors to stop their involvement for any unstated reasons; 6) Operating
      fairness of opportunity; 7) Differentiating qualitative research methods and
      public involvement activities; 8) Working sensitively; 9) Being conscious of
      confidentiality and 10) Valuing, acknowledging and rewarding public involvement.
      We looked to see whether any other similar approaches to helping researchers
      address potential ethical issues when working with the public on designing
      studies have been published and to our knowledge none exist. Our framework is
      presented as a draft and believe that it would now benefit from input from
      researchers and the public to gauge how useful it is and whether there are any
      other possible situations that it might need to cover. ABSTRACT: The current
      paper highlights real life examples of how ethical issues can arise during public
      involvement activities at the research design stage. We refer to "the research
      design stage" as the time between the generation of the research ideas and when
      formal permissions to start the work including ethical approval are granted. We
      argue that although most researchers work ethically at this early stage, some may
      still benefit from being informed about ethically conscious approaches to
      involving the public. The paper highlights 10 ethical issues that we have
      observed with involving the public at the research design stage. We provide
      examples of these observed scenarios to illustrate the issues and make
      suggestions for how they can be avoided to help researchers become more ethically
      conscious when involving the public at the research design stage. Currently the
      draft framework comprises: 1) Allocating sufficient time for public involvement;
      2) Avoiding tokenism; 3) Registering research design stage public involvement
      work with NHS Research & Development Trust Office at earliest opportunity; 4)
      Communicating clearly from the outset; 5) Entitling public contributors to stop
      their involvement for any unstated reasons; 6) Operating fairness of opportunity;
      7) Differentiating qualitative research methods and public involvement
      activities; 8) Working sensitively; 9) Being conscious of confidentiality and 10)
      Valuing, acknowledging and rewarding public involvement. The draft framework will
      help researchers to recognise the ethical issues when involving the public and is
      intended to be used voluntarily in a self-regulatory way. We believe that the
      draft framework requires further consultation and input from the wider research
      community and the public before endorsement by national UK bodies such as INVOLVE
      and the Health Research Authority (HRA).

PMID- 29062532
TI  - Co-producing public involvement training with members of the public and research
      organisations in the East Midlands: creating, delivering and evaluating the lay
      assessor training programme.
AB  - PLAIN ENGLISH SUMMARY: Members of the public share their views with researchers
      to improve health and social care research. Lay assessing is one way of doing
      this. This is where people, drawing upon personal and general life experience,
      comment on material, such as grant applications and patient information, to
      highlight strengths and weaknesses and to suggest improvements. This paper
      reports on setting up a training programme for lay assessors. Meetings were held
      between interested public and staff from research organisations. People discussed
      what lay assessing is, why they want to do it, skills and support needed and if
      training was wanted. They were invited to form a group to develop the training
      together. Training was delivered in the East Midlands. People who attended gave
      their thoughts about it by completing questionnaires and joining a feedback
      event. The group developed the structure of the training programme together and
      it oversaw the development of the training content by individual members. People
      who attended training reported feeling more confident about lay assessing. This
      was particularly so for those who had not done lay assessing before. They
      indicated how valuable it was to talk with others at the training. Our findings
      support the National Institute for Health Research recommendations for improving
      learning and development for public involvement in research. This project has
      created a solid base for local research organisations to work together in public
      involvement training. Lay assessor training is now part of a wider programme of
      shared resources called the Sharebank. ABSTRACT: Background Involving members of
      the public in research can improve its quality and incorporate the needs and
      views of patients. One method for doing this is lay assessing, where members of
      the public are consulted to improve research materials. This paper documents the
      establishment of a pilot training programme for lay assessors. It describes a way
      of working that embodies a regional, cross-organisational approach to co
      producing training with members of the public. Methods Open meetings, led by AH,
      were held for existing and aspiring lay assessors to define lay assessing,
      motivations for doing it, skills required, associated learning and development
      needs, and to gauge interest for training. Those who attended meetings, including
      members of the public and staff, were invited to form a working group to co
      produce the training programme. Training was delivered in modules at two centres
      in the East Midlands and evaluated through participant feedback at the end of
      each module and at an evaluation event. Feedback was through a mix of Likert
      scale scoring, open text and verbal responses. Results Discussions from the open
      meetings informed the development of the training by the working group. Led by
      AH, the working group, as a whole, co-produced the structure and format of the
      training and oversaw training content development by individuals within the
      group. Training was well-received by participants. Feedback through Likert
      scoring (n = 14) indicated higher feelings of confidence in knowledge of relevant
      subject matter and in fulfilling the lay assessor role, particularly amongst
      those who had not done lay assessing before. Opportunities that the training
      afforded for interaction between participants - sharing of varied experiences and
      knowledge - and a 'learn by doing' approach was of particular value, as indicated
      by 10 responses to open-ended questions. Conclusions This project has created a
      solid foundation for collaboration between research organisations in the East
      Midlands in devising and delivering training in public involvement together. Our
      evaluation provides evidence in support of National Institute for Health Research
      (NIHR) recommendations on principles for learning and development for public
      involvement in research.

PMID- 29062533
TI  - The consultation of rugby players in co-developing a player health study:
      feasibility and consequences of sports participants as research partners.
AB  - PLAIN ENGLISH SUMMARY: Many funding bodies within the United Kingdom and globally
      have encouraged public involvement in research. The Department of Health has also
      called public involvement a sign of good research. Despite the wide acceptance of
      public involvement improving many aspects of research, from its design to its
      communication, involvement has varied levels of implementation across different
      fields of research. Sports people have rarely been involved in research, partly
      as this research tends not to be funded by mainstream funding bodies. This may
      lead to a lower research quality, not founded in player ('service user')
      experiences. When creating a study of former rugby player health, we were very
      keen to involve rugby players, understand their thoughts on player health, and
      their playing experiences. This article explains how rugby players were involved
      in several ways, but mainly in group discussions during the design stage. These
      groups helped to inform our study's aims and questionnaire, ensure the
      questionnaire would capture player experiences and answer questions relevant to
      players, that they would like to understand after their participation in rugby.
      We found that these groups were easy to arrange, and that in only one session
      with each group, we were given many ideas of how to improve the questionnaire and
      study. We believe that other studies in sports should involve sports people, and
      that this is a useful activity that will change data collection forms and
      processes, improving the research, helping researchers, and making studies more
      suitable for players who take part in them. ABSTRACT: Background Patient and
      public involvement ('involvement') in the UK has increased in accordance with
      funding requirements, patient-centered health policy initiatives and reporting of
      the positive impact of involvement for those involved, research and researchers.
      However, involvement has not been implemented equally across all disease areas
      and populations. The aim of this process was to involve rugby players across the
      research cycle of a player health study, ensure the study is player-centred, and
      that players had approved and informed the design of the study and its
      questionnaire from their playing experiences. Methods Two group discussions were
      undertaken with current students who were playing rugby at a Collegiate
      University. All male and female University rugby players and two College rugby
      teams were approached to become involved. Sessions were chaired by a player-lead
      using a topic guide and were audio-recorded and transcribed. Player suggestions
      were extracted by the player-lead and discussed within the study team for
      inclusion in the player health study and its questionnaire. Results Players
      readily engaged with the sessions and made many contributions to the development
      of the study and the questionnaire. Players discussed whether certain topics were
      being collected satisfactorily, and whether the questionnaire would encompass
      their playing experiences or that of other players. Players suggested where
      answers might be less reliable, and ways in which this could be improved. Players
      recommended additions to the questionnaire, and questioned researchers on the
      choice of language, motivation for question inclusion and if measures were
      standardised or novel. Alterations were made to the questionnaire based on
      suggestions, where these were agreed by the study team. Conclusions Involving a
      group of players in the design of a player health study and questionnaire was not
      an arduous process and was rewarding for researchers. The process resulted in
      numerous alterations to the questionnaire and its functionality, which may
      improve response rate, the experience of players participating in the player
      health study, and their ability to report relevant information aligned with their
      previous experience. Player involvement in research was feasible to implement and
      improved not only the questionnaire, but also researcher confidence in the
      project and player experiences being accurately captured and leading a reliable
      data collection processes in a population with the potential for cultural bias to
      affect the ascertainment of health, pain and injury.

PMID- 29062534
TI  - Stakeholder involvement in systematic reviews: a protocol for a systematic review
      of methods, outcomes and effects.
AB  - PLAIN ENGLISH SUMMARY: Researchers are expected to actively involve stakeholders
      (including patients, the public, health professionals, and others) in their
      research. Although researchers increasingly recognise that this is good practice,
      there is limited practical guidance about how to involve stakeholders. Systematic
      reviews are a research method in which international literature is brought
      together, using carefully designed and rigorous methods to answer a specified
      question about healthcare. We want to investigate how researchers have involved
      stakeholders in systematic reviews, and how involvement has potentially affected
      the quality and impact of reviews. We plan to bring this information together by
      searching and reviewing the literature for reports of stakeholder involvement in
      systematic reviews. This paper describes in detail the methods that we plan to
      use to do this. After carrying out comprehensive searches for literature, we
      will: 1. Provide an overview of identified reports, describing key information
      such as types of stakeholders involved, and how. 2. Pick out reports of
      involvement which include detailed descriptions of how researchers involved
      people in a systematic review and summarise the methods they used. We will
      consider who was involved, how people were recruited, and how the involvement was
      organised and managed. 3. Bring together any reports which have explored the
      effect, or impact, of involving stakeholders in a systematic review. We will
      assess the quality of these reports, and summarise their findings. Once
      completed, our review will be used to produce training resources aimed at helping
      researchers to improve ways of involving stakeholders in systematic reviews.
      ABSTRACT: Background There is an expectation for stakeholders (including
      patients, the public, health professionals, and others) to be involved in
      research. Researchers are increasingly recognising that it is good practice to
      involve stakeholders in systematic reviews. There is currently a lack of evidence
      about (A) how to do this and (B) the effects, or impact, of such involvement. We
      aim to create a map of the evidence relating to stakeholder involvement in
      systematic reviews, and use this evidence to address the two points above.
      Methods We will complete a mixed-method synthesis of the evidence, first
      completing a scoping review to create a broad map of evidence relating to
      stakeholder involvement in systematic reviews, and secondly completing two
      contingent syntheses. We will use a stepwise approach to searching; the initial
      step will include comprehensive searches of electronic databases, including
      CENTRAL, AMED, Embase, Medline, Cinahl and other databases, supplemented with pre
      defined hand-searching and contacting authors. Two reviewers will undertake each
      review task (i.e., screening, data extraction) using standard systematic review
      processes. For the scoping review, we will include any paper, regardless of
      publication status or study design, which investigates, reports or discusses
      involvement in a systematic review. Included papers will be summarised within
      structured tables. Criteria for judging the focus and comprehensiveness of the
      description of methods of involvement will be applied, informing which papers are
      included within the two contingent syntheses. Synthesis A will detail the methods
      that have been used to involve stakeholders in systematic reviews. Papers from
      the scoping review that are judged to provide an adequate description of methods
      or approaches will be included. Details of the methods of involvement will be
      extracted from included papers using pre-defined headings, presented in tables
      and described narratively. Synthesis B will include studies that explore the
      effect of stakeholder involvement on the quality, relevance or impact of a
      systematic review, as identified from the scoping review. Study quality will be
      appraised, data extracted and synthesised within tables. Discussion This review
      should help researchers select, improve and evaluate methods of involving
      stakeholders in systematic reviews. Review findings will contribute to Cochrane
      training resources.

PMID- 29062535
TI  - Working with public contributors to improve the patient experience at the
      Manchester Clinical Research Facility: an evaluation of the Experience Based
      Design approach.
AB  - PLAIN ENGLISH SUMMARY: The Experience Based Design (EBD) approach involves
      patients, staff and members of the public working together to improve a service.
      This paper evaluates the methods that are used to involve patients and members of
      the public in a project that aimed to improve the patient experience at
      Manchester Clinical Research Facility (MCRF). The aim was to explore what helps
      staff and members of the public to work well together. An evaluation
      questionnaire was used to get feedback from staff and public contributors.
      Questions included whether each person felt that they were able to shape the
      project; if they received enough training; whether they had enough time to
      complete each task; how well they thought the group worked together; and what
      could be improved. The findings showed that both staff and public contributors
      felt valued and that they were able to shape the project from the beginning.
      Training in EBD and research methodology, and providing enough time to complete
      each task helped to build relationships and increase confidence when contributing
      to the project. Personal benefits included a feeling of ownership over a
      worthwhile and rewarding project, increased awareness of public involvement and
      gaining new skills. The recommendations for successful involvement of patients
      and the public in EBD projects will hopefully be helpful for similar projects in
      the future. ABSTRACT: Background The Experience Based Design (EBD) approach
      promotes the effective involvement of patients and public contributors by
      enabling patients, public contributors and staff to co-design projects that aim
      to improve the patient experience. This approach allows patients and members of
      the public to have a role in shaping and improving current services. This paper
      aims to evaluate the EBD process from a public involvement perspective, exploring
      the barriers and facilitators to building successful working relationships.
      Methods An open-ended evaluation questionnaire was developed to gain feedback
      from staff and public contributors who co-produced an EBD project that aimed to
      improve the patient experience at Manchester CRF. Questions explored what worked
      well, how the project could be improved, and the benefits of being involved.
      Results Our findings highlight the importance of providing opportunities for
      staff, patients and members of the public to build relationships in order to feel
      confident in voicing their opinions. This can be achieved by training both staff
      and public contributors in EBD methodology to reduce any power imbalance that may
      exist. Negotiating adequate time to complete tasks and debate the best way
      forward also allows everyone to fully contribute to the project. Each individual
      felt that their contribution was valued and that they shaped the final action
      plan. Both public contributors and staff listed a number of personal benefits
      from their involvement in the project. This included a feeling of ownership over
      a worthwhile and rewarding project, increased awareness of public involvement in
      EBD projects and gaining new skills. Conclusion This evaluation provides
      recommendations for best practice for effectively involving public contributors
      in an EBD methodology. These findings aim to encourage a more consistent approach
      to EBD across organisations.

PMID- 29062536
TI  - Involving seldom-heard groups in a PPI process to inform the design of a proposed
      trial on the use of probiotics to prevent preterm birth: a case study.
AB  - PLAIN ENGLISH SUMMARY: When designing clinical trials it is important to involve
      members of the public, who can provide a view on what may encourage or prevent
      people participating and on what matters to them. This is known as Public and
      Patient Involvement (PPI). People from minority ethnic groups are often less
      likely to take part in clinical trials, but it is important to ensure they are
      able to participate fully so that health research and its findings are relevant
      to a wide population. We are preparing to conduct a randomised controlled trial
      (RCT) to test whether taking probiotic capsules can play a role in preventing
      preterm birth. Women from some minority ethnic groups, for example women from
      West Africa, and those who are from low-income groups are more likely to suffer
      preterm births. Preterm birth can lead to extra costs to health services and
      psychosocial costs for families. In this article we describe how we engaged women
      in discussion about the design of the planned trial, and how we aim to use our
      findings to ensure the trial is workable and beneficial to women, as well as to
      further engage service users in the future development of the trial. Four
      socially and ethnically diverse groups of women in East London took part in
      discussions about the trial and contributed their ideas and concerns. These
      discussions have helped to inform and improve the design of a small practice or
      'pilot' trial to test the recruitment in a 'real life' setting, as well as
      encourage further PPI involvement for the future full-scale trial. ABSTRACT:
      Background Patient and public involvement (PPI) is an important tool in
      approaching research challenges. However, involvement of socially and ethnically
      diverse populations remains limited and practitioners need effective methods of
      involving a broad section of the population in planning and designing research.
      Methods In preparation for the development of a pilot randomised controlled trial
      (RCT) on the use of probiotics to prevent preterm birth, we conducted a public
      consultation exercise in a socially disadvantaged and ethnically diverse
      community. The consultation aimed to meet and engage local service users in
      considering the acceptability of the proposed protocol, and to encourage their
      participation in future and ongoing patient and public involvement activities.
      Four discussion groups were held in the community with mothers of young children
      within the proposed trial region, using an inclusive approach that incorporated a
      modified version of the Nominal Group Technique (NGT). Bringing the consultation
      to the community supported the involvement of often seldom-heard participants,
      such as those from minority ethnic groups. Results The women involved expressed a
      number of concerns about the proposed protocol, including adherence to the
      probiotic supplement regimen and randomisation. The proposal for the RCT in
      itself was perceived as confirmation that probiotic supplements had potentially
      beneficial effects, but also that they had potentially harmful side-effects. The
      complexity of the women's responses provided greater insights into the challenges
      of even quite simple trial designs and enabled the research team to take these
      concerns into account while planning the pilot trial. Conclusions The use of the
      NGT method allowed for a consultation of a population traditionally less likely
      to participate in medical research. A carefully facilitated PPI exercise can
      allow members to express unanticipated concerns that may not have been elicited
      by a survey method. Findings from such exercises can be utilised to improve
      clinical trial design, provide insight into the feasibility of trials, and enable
      engagement of often excluded population groups.

PMID- 29062537
TI  - Tea, talk and technology: patient and public involvement to improve connected
      health 'wearables' research in dementia.
AB  - PLAIN ENGLISH SUMMARY: There are a growing number of mobile phones, watches and
      electronic devices which can be worn on the body to track aspects of health and
      well-being, such as daily steps, sleep and exercise. Dementia researchers think
      that these devices could potentially be used as part of future research projects,
      for example to help spot changes in daily activity that may signal the early
      symptoms of dementia. We asked a range of older people, including people living
      with dementia and their carers, to participate in interactive discussions about
      how future participants might find using these devices as part of research
      projects. We also invited volunteers to borrow a range of devices to test at
      home, giving them further insights. Discussions revealed that people were
      generally supportive of this type of research, provided they gave informed
      consent and that devices were discreet, comfortable and easy to use. They also
      valued technical support and regular feedback on study progress to encourage
      ongoing participation. These findings were used to develop a pool of devices for
      researchers, with computer software and written guidance to help plan, design and
      support studies. Our work shows that when given the right opportunities, people
      who are affected by dementia can provide valuable insights that can enhance the
      design, delivery and quality of future research. ABSTRACT: Background
      Increasingly, researchers are recognising the potential for connected health
      devices, including smartphones and smartwatches, to generate high resolution data
      about patterns of daily activity and health outcomes. One aim of the Dementias
      Platform UK (DPUK) project is to provide researchers with a secure means to
      collect, collate and link data generated by such devices, thereby accelerating
      this type of research in the field of dementia. We aimed to involve members of
      the public in discussions about the acceptability and feasibility of different
      devices and research designs to inform the development of a device pool, software
      platform and written guidance to support future studies. Methods Over 30 people
      attended a series of interactive workshops, drop-in sessions and meetings in
      Greater Manchester. This included people living with dementia and cognitive
      impairments, carers and people without memory problems. Discussions were tailored
      to suit different audiences and focused on the feasibility and acceptability of a
      range of different wearable devices and research designs. We also invited
      volunteers to borrow a device to test at home, enabling further insights from
      hands-on interactions with devices. Results Discussions revealed that people were
      supportive of connected health dementia research in principle, provided they gave
      informed consent and that devices were discreet, comfortable and easy to use.
      Moreover, they recommended technical support and regular feedback on study
      progress to encourage ongoing participation. Conclusion By using a range of
      discussion-based and practical activities, we found it was feasible to involve
      people affected by dementia and use their insights to shape the development of a
      software platform and device pool to support future connected health dementia
      research. We recommend that researchers planning such studies in future pay
      adequate attention to designing suitable participant information, technical
      support and mechanisms of providing study progress updates to support sustained
      engagement from participants.

PMID- 29062539
TI  - Patient organization involvement and the challenge of securing access to
      treatments for rare diseases: report of a policy engagement workshop.
AB  - PLAIN ENGLISH SUMMARY: Patients with rare diseases often help to develop new
      treatments for their conditions. But once developed, those treatments are
      sometimes priced too high for many patients to access them. We became aware that
      this is a problem in the course of a social science research project that
      examines the place of rare diseases in health policy. We therefore organized a
      two-day workshop to try and understand why this problem occurs and what might be
      done about it. The people who participated in our workshop were: representatives
      of rare disease patient organizations, experts in matters of drug regulation and
      assessment of new health technologies, consultants involved with companies
      producing treatments for rare diseases, and social scientists researching related
      issues. The main conclusions to emerge from the discussions were as follows:
      Problems of access to treatments for rare diseases are not just due to high
      prices; procedures for regulating, assessing and delivering new treatments also
      need to be better organized. Patients and patient organizations have much to
      contribute to this process. However, their resources are often very limited.
      Consequently, more needs to be done to help them use those resources as
      effectively as possible. In particular, regulators and healthcare providers need
      to ensure that their procedures are clear and efficiently managed, so as not to
      waste patient organizations' time and money. Clearer guidance is needed on what
      patient organizations can do to provide evidence of the effectiveness of new
      drugs. Insights gained in tackling rare diseases might also be applicable to
      common disorders. Finally, the consequences of Brexit for UK policies on rare
      diseases urgently need to be assessed. ABSTRACT: Since the enactment of orphan
      drug legislation in the USA, Europe and several other countries, an increasing
      number of treatments for rare diseases have been developed and many of them been
      approved for marketing. However, such treatments tend to be priced very high, and
      access to effective treatments remains a major challenge for patients with rare
      diseases - despite active involvement of patients and their support organizations
      in various stages of basic and applied research and commercial development. In
      order to allow patients to benefit from treatments proved effective for their
      diseases, we need to better understand why this challenge persists, and what
      steps might be taken to address it. To that end, we organized a policy-engagement
      workshop, bringing together individuals and organizations with direct experience
      of trying to secure access to a treatment for a rare disease along with
      individuals with relevant expertise in regulatory and commissioning processes for
      new medicines. With additional input from social scientists who offered different
      perspectives on the value of patient involvement, the workshop aimed to initiate
      a dialogue among the participants about how to address the challenge in a
      sustainable manner. Discussions at the workshop stressed that active involvement
      of patients is as valuable in the regulatory and commissioning processes as in
      the research and development of new medicines. However, it also highlighted
      certain risks and costs associated with such involvement. These include the costs
      of adjusting to abrupt changes in regulatory and commissioning processes, and the
      risk of being perceived as too close to commercial interests. To optimize use of
      scarce resources and ensure continuing active involvement, such risks and costs
      need to be better managed. Participants also noted that, owing to advances in
      genomic technologies, common diseases are also becoming divided into rare sub
      categories, which are equally eligible for orphan drug designation. Consequently,
      involvement of wider patient communities beyond rare disease communities will be
      critical for continuing discussions about patients' involvement in regulatory and
      commissioning processes, and to consider how patients and their support
      organizations can best work with other stakeholders - including companies,
      regulators and policymakers - to ensure access to effective medicines.

PMID- 29062538
TI  - GRIPP2 reporting checklists: tools to improve reporting of patient and public
      involvement in research.
AB  - BACKGROUND: While the patient and public involvement (PPI) evidence base has
      expanded over the past decade, the quality of reporting within papers is often
      inconsistent, limiting our understanding of how it works, in what context, for
      whom, and why. OBJECTIVE: To develop international consensus on the key items to
      report to enhance the quality, transparency, and consistency of the PPI evidence
      base. To collaboratively involve patients as research partners at all stages in
      the development of GRIPP2. METHODS: The EQUATOR method for developing reporting
      guidelines was used. The original GRIPP (Guidance for Reporting Involvement of
      Patients and the Public) checklist was revised, based on updated systematic
      review evidence. A three round Delphi survey was used to develop consensus on
      items to be included in the guideline. A subsequent face-to-face meeting produced
      agreement on items not reaching consensus during the Delphi process. RESULTS: One
      hundred forty-three participants agreed to participate in round one, with an 86%
      (123/143) response for round two and a 78% (112/143) response for round three.
      The Delphi survey identified the need for long form (LF) and short form (SF)
      versions. GRIPP2-LF includes 34 items on aims, definitions, concepts and theory,
      methods, stages and nature of involvement, context, capture or measurement of
      impact, outcomes, economic assessment, and reflections and is suitable for
      studies where the main focus is PPI. GRIPP2-SF includes five items on aims,
      methods, results, outcomes, and critical perspective and is suitable for studies
      where PPI is a secondary focus. CONCLUSIONS: GRIPP2-LF and GRIPP2-SF represent
      the first international evidence based, consensus informed guidance for reporting
      patient and public involvement in research. Both versions of GRIPP2 aim to
      improve the quality, transparency, and consistency of the international PPI
      evidence base, to ensure PPI practice is based on the best evidence. In order to
      encourage its wide dissemination this article is freely accessible on The BMJ and
      Research Involvement and Engagement journal websites.

PMID- 29062540
TI  - Recruiting patients as partners in health research: a qualitative descriptive
      study.
AB  - PLAIN ENGLISH SUMMARY: Increasingly, funders and researchers want to partner with
      patients in health research, but it can be challenging for researchers to find
      patient partners. More than taking part in research as participants, patient
      partners help design, carry out and manage research projects. The goal of this
      study was to describe ways that patient partners have been recruited by
      researchers and patient engagement leads (individuals within organizations
      responsible for promoting and supporting patients as research partners). We
      talked with researchers and patient engagement leads in Canada and the United
      Kingdom, as well as a patient representative. We found three ways that could help
      researchers and patients find each other. One way is a case-by-case basis, where
      patients are often sought with experience of a health condition that is the focus
      of the research. The other ways involved directories where projects were posted
      and could be found by patients and researchers, or a third party matched patients
      with research projects. We found four recruitment strategies:Social
      marketingCommunity outreachHealth systemPartnering with other organizations
      (e.g., advocacy groups) There are many influences on finding, selecting and
      retaining patient partners: patient characteristics, the local setting, the
      opportunity, work climate, education and support. We hope study results will
      provide a useful starting point for research teams in recruiting their patient
      partners. ABSTRACT: Background Patient engagement in clinical trials and other
      health research continues to gain momentum. While the benefits of patient
      engagement in research are emerging, relatively little is known about recruiting
      patients as research partners. The purpose of this study was to describe
      recruitment strategies and models of recruiting patients as partners in health
      research. Methods Qualitative descriptive study. Thirteen patient engagement
      leads and health researchers from Canada and the United Kingdom, as well as one
      patient representative from a national patient organization (7 female) completed
      semi-structured interviews. Results Recruitment infrastructures available to
      respondents varied, but could be categorized into three models including the
      traditional, third-party and directory models. Four categories of recruitment
      strategies were identified, representing multiple ways of recruiting patient
      partners: social marketing recruitment, community outreach recruitment, health
      system recruitment, and partnering recruitment. Conclusions Multiple recruitment
      strategies were identified for engaging patient partners in research, and some
      common factors influenced recruitment. Study findings contribute to the evidence
      base in patient engagement and provide guidance for research teams to help
      identify potential recruitment methods for their patient partners.

PMID- 29062541
TI  - Using the nominal group technique to involve young people in an evidence
      synthesis which explored 'risk' in inpatient mental healthcare.
AB  - PLAIN LANGUAGE SUMMARY: We conducted a review of research on the topic of 'risk'
      in hospital based mental health care for young people aged 11-18. We wanted to
      include a contribution from young people alongside other stakeholders with
      expertise to guide the research team in decisions made setting parameters for the
      review. To achieve this, we held a stakeholder group meeting. We used the nominal
      group technique, a method designed to create a structure and a process for
      getting feedback from a group of people in a way that allows everyone to have an
      equal say. In this study, we show how our use of this approach enabled our
      stakeholder group to shape the focus of our study towards an area of more
      importance and relevance to them. ABSTRACT:  BACKGROUND: In this paper we
      demonstrate how our application of the nominal group technique was used as a
      method of involving young people with previous experience of using inpatient
      mental health services in an evidence synthesis. METHODS: Nominal group technique
      is an approach to group decision-making that places weight on all participants
      having an equal opportunity to express a view, and to influence decisions which
      are made. It is an effective way to enable people who might otherwise be excluded
      from decision-making to contribute. RESULTS: In this study, the focus of the
      evidence synthesis was significantly shaped following using the nominal group
      technique in our stakeholder advisory group meeting. The young people present in
      the group invited the research group to think differently about which 'risks'
      were important, to consider how young people conceptualised risk differently,
      focussing on risks with long term impact and quality of life implications, rather
      than immediate clinical risks. CONCLUSIONS: Using the nominal group technique
      with young people did offer a method of promoting the equality of decision making
      within a stakeholder advisory group to an evidence synthesis project, but care
      needs to be taken to invite sufficient young people to attend so they can be
      proportionally represented.

PMID- 29062542
TI  - Understanding Plain English summaries. A comparison of two approaches to improve
      the quality of Plain English summaries in research reports.
AB  - PLAIN ENGLISH SUMMARY: There is a need for the authors of research reports to be
      able to communicate their work clearly and effectively to readers who are not
      familiar with the research area. The National Institute for Health Research
      (NIHR), along with a number of other funding bodies and journals, require
      researchers to write short lay summaries, often termed plain English summaries
      (PESs), to make research accessible to the general public. Because many
      researchers write using technical, specialised language, particularly in
      scientific reports, writing PESs can be challenging. In this study we looked at
      how to improve the quality of PESs. We took PESs which had been submitted to the
      NIHR Journals Library and asked authors to rewrite them using new guidance. We
      also asked an independent medical writer to edit the summaries. We measured the
      quality of these three versions (original summary, rewritten summary and edited
      summary) in two ways. First, we asked a group of people who were not specialists
      in the subject area to read and rate how easy the summaries were to understand.
      Secondly, we used a well-known measure called the Flesch reading ease score to
      assess how easy the PESs were to read. We found that there was no difference in
      how easy people found the summaries to understand across the three versions.
      However, the PESs that were rewritten by the authors and that were edited by the
      independent medical writer were both easier to read than the originals. This
      shows that PESs can be improved and for organisations who feel that employing an
      independent writer to edit summaries, providing clear, practical guidance to
      authors may be a cost-effective alternative. ABSTRACT:  BACKGROUND: Plain English
      summaries (PES) or lay summaries are often included as part of research reports
      and journal articles. These summaries are vital to ensure that research findings
      are accessible and available to non-specialist audiences, for example patients
      and members of the public. Writing a PES requires the adoption of a different
      style than is generally used in a traditional scientific report, and researchers
      can find this challenging. This study explored two possible ways to improve the
      quality of PESs in the NIHR Journals Library: 1) Providing enhanced guidance to
      authors and asking them to rewrite the PES and 2) Employing an independent
      medical writer to edit the PES. METHODS: We compared the three versions of the
      PES (original, author rewritten and independent writer edited) to assess 1) how
      easy they were to understand and 2) how easy they were to read. In order to
      establish how easy PESs were to understand, a group of 60 public reviewers read a
      set of summaries and rated them on a four point scale from "Did not understand"
      to "Understood all". The Flesch reading ease score was used to measure how easy
      the summaries were to read. RESULTS: Results indicated no significant difference
      across the three versions of the PES in terms of ease of understanding. However,
      both the author rewritten and independent writer edited versions were
      significantly easier to read than the original. There was no significant
      difference in ease of reading between these two versions. CONCLUSION: These
      findings suggest that employing independent medical writers to edit PESs and
      providing clear, practical guidance to authors are two ways in which the
      readability of PESs could be improved. Results have implications for journal
      editors and publishers seeking to enhance accessibility and availability of
      research findings.

PMID- 29062543
TI  - "Is all the stuff about neurons necessary?" The development of lay summaries to
      disseminate findings from the Newcastle Cognitive Function after Stroke (COGFAST)
      study.
AB  - PLAIN ENGLISH SUMMARY: Why did we do this study? It can be difficult for
      scientists to communicate their research findings to the public. This is partly
      due to the complexity of translating scientific language into words that the
      public understand. Further, it may be hard for the public to find out about and
      locate information about research studies. We aimed to adapt some scientific
      articles about the links between dementia and stroke into lay summaries to be
      displayed online for the general public. How did we do it? We collaborated with
      five people from a volunteer organisation, VOICENorth. They took part in two
      group discussions about studies reporting on the link between dementia and
      stroke, and selected four studies to translate into lay summaries and display on
      a website. We discussed the layout and language of the summaries and made
      adaptations to make them more understandable to the general public. What did we
      find? We were able to work with members of the public to translate research
      findings into lay summaries suitable for a general audience. We made changes to
      language and layout including the use of 'question and answer' style layouts, the
      addition of a reference list of scientific terms, and removing certain words.
      What does this mean? Working with members of the public is a realistic way to
      create resources that improve the accessibility of research findings to the wider
      public. ABSTRACT: Background Scientific research is often poorly understood by
      the general public and difficult for them to access. This presents a major
      barrier to disseminating and translating research findings. Stroke and dementia
      are both major public health issues, and research has shown lifestyle measures
      help to prevent them. This project aimed to select a series of studies from the
      Newcastle Cognitive Function after Stroke cohort (COGFAST) and create lay
      summaries comprehensible and accessible to the public. Methods We used a focus
      group format to collaborate with five members of the public to review COGFAST
      studies, prioritise those of most interest to the wider public, and modify the
      language and layout of the selected lay summaries. Focus groups were audio-taped
      and the team used the data to make iterative amendments, as suggested by members
      of the public, to the summaries and to a research website. We calculated the
      Flesch reading ease and Flesch-Kincaid grade level for each summary before and
      after the changes were made. Results In total, we worked with five members of the
      public in two focus groups to examine draft lay summaries, created by
      researchers, relating to eight COGFAST studies. Members of the public prioritised
      four COGFAST lay summaries according to the importance of the topic to the
      general public. We made a series of revisions to the summaries including the use
      of 'question and answer' style layouts, the addition of a glossary, and the
      exclusion of scientific jargon. Group discussion highlighted that lay summaries
      should be engaging, concise and comprehensible. We incorporated suggestions from
      members of the public into the design of a study website to display the
      summaries. The application of existing quantitative tools to estimate readability
      resulted in an apparently paradoxical increase in complexity of the lay summaries
      following the changes made. Conclusion This study supports previous literature
      demonstrating challenges in creating generic guidelines for researchers to create
      lay summaries. Existing quantitative metrics to assess readability may be
      inappropriate for assessing scientific lay summaries. We have shown it is
      feasible and successful to involve members of the public to create lay summaries
      to communicate the findings of complex scientific research. Trial registration
      Not applicable to the lay summary project.

PMID- 29062544
TI  - Patient involvement in guidelines is poor five years after institute of medicine
      standards: review of guideline methodologies.
AB  - PLAIN ENGLISH SUMMARY: The 2011 standards for trustworthy development of
      healthcare guidelines published by the United States-based Institute of Medicine
      recommend that guideline developers involve patients and public representatives
      in the development process. The standards recommend that (1) patients and the
      public be actively involved as members on guideline development panels and (2)
      guideline developers seek patient and public input during review of the draft
      guideline. In this study, researchers reviewed the patient and public involvement
      strategies of guideline developers in the United States by looking at websites
      and guideline development practices. Of 101 organizations reviewed, only 8%
      require patient and public involvement on guideline development groups; 15%
      sometimes require it or describe it as optional. Only 24% of guideline developers
      always post draft guidelines for public comment. Thirteen percent of guideline
      developers ask patients or patient organizations to review draft guidelines at
      least some of the time. Only 20% of guideline developers create patient-targeted
      guideline products (e.g. patient summaries of guidelines). These low numbers show
      that there is a substantial gap between standards for patient and public
      involvement in guideline development and what is actually happening. This is a
      missed opportunity, as patient and public contributions to guideline development
      include assessing guideline priorities, introducing new topics, identifying
      important populations and outcomes, suggesting whether findings are meaningful,
      prompting holistic approaches to care, assessing how recommendations interact
      with patient values, and writing plain-language guideline versions. Guideline
      developers must commit to prioritizing patient and public involvement as one part
      of trustworthy guideline development. ABSTRACT:  BACKGROUND: The United States
      based Institute of Medicine 2011 standards for trustworthy clinical practice
      guideline development recommended patient and public involvement in guideline
      development via participation by patients and public representatives on guideline
      development groups and via external review and public comment strategies.
      Guideline developer compliance with these standards has not been assessed. This
      study aimed to identify the frequency with which United States guideline
      developers are employing participation, consultation, and communication patient
      and public involvement strategies. METHODS: Two reviewers independently extracted
      current patient and public involvement strategies of independent guideline
      developers, either (1) an organizational member of the Guidelines-International
      Network North America and/or (2) having >=2 guidelines in the National Guideline
      Clearinghouse between March 2011 and November 2015. Publicly available
      information was extracted from guideline developers' websites, methodology
      manuals, and guidelines between November 2015 and December 2016. Disagreements
      were resolved by discussion. RESULTS: Of 101 organizations meeting inclusion
      criteria, only 8% require patient/public involvement on guideline development
      groups; 15% sometimes require it or describe it as optional. Only 24% always
      utilize public comment on draft guidelines; 13% engage patients/public in
      external review at least some of the time. Twenty percent of developers create
      patient-targeted guideline products. CONCLUSIONS: There remains a substantial gap
      between patient/public involvement standards for guideline development and
      practice in the United States, even 5 years after publication of Institute of
      Medicine standards. This is a missed opportunity, as patient and public
      contributions to guideline development include assessing guideline priorities,
      introducing new topics, identifying key populations and outcomes, informing
      whether findings are meaningful, prompting holistic approaches to care, assessing
      how recommendations interact with patient values, and writing plain-language
      guideline versions. Guideline developers must commit to prioritizing patient and
      public involvement as one element of trustworthy guideline development.

PMID- 29062545
TI  - The impact of involvement on researchers: a learning experience.
AB  - PLAIN ENGLISH SUMMARY: The impacts of involvement in research are often described
      in terms of the difference made to the research, the people involved and less
      frequently the researchers. This paper focuses on the researchers' experiences of
      involvement, based on an evaluation of a pilot project supporting patient/carer
      involvement in research at Parkinson's UK. Telephone interviews were conducted
      with researchers from eight different research projects with involvement. The
      researchers reported gaining new knowledge from patients and carers. They used
      this knowledge to change their project designs, interventions and new devices.
      They also gained new skills in communicating with the public. Meeting patients
      for the first time had a profound impact on some researchers, causing a change in
      their professional values. Face-to-face contact seemed particularly important to
      gain a sense of the 'people behind the data', which suggests such meetings may
      result in impacts beyond those typically achieved through an exchange of
      documents. Involvement also influenced one researcher's choices and preferences,
      in terms of who to ask to take part in their study In summary, researchers often
      learn something new from talking to patients and carers. Facilitating this
      conversation seems important to maximise the impact of this learning. In future,
      it might be helpful for evaluations of involvement to ask researchers in more
      detail about what they learnt from patients/carers and how they applied their new
      skills and knowledge. This may help to understand how involvement can influence
      researchers' thinking to have an impact on research. ABSTRACT: Background The
      impacts of patient/public involvement are often described in terms of the
      difference made to the research, the researchers and the people involved.
      Involvement often impacts on research by influencing the design, delivery and
      dissemination. Patients/the public report gaining new skills and knowledge,
      increased self-confidence, and satisfaction from making a difference. There are
      fewer reports of the impacts on researchers. This paper discusses the findings
      from an evaluation of a pilot project supporting patient/carer involvement in
      research at Parkinson's UK, focusing on the researchers' experiences. Methods
      Semi-structured telephone interviews were conducted with one researcher from each
      of the eight research projects which involved patients/carers in the pilot. The
      findings were analysed using theoretical thematic analysis. Results and
      discussion Learning can be described as acquiring new knowledge, behaviours,
      skills, values, or preferences. The researchers' reports reflected these
      different types of learning. They reported gaining new knowledge from patients
      and carers, which they recognised as distinct from their textbook knowledge of
      the condition. They used this learning to change their project designs and their
      new interventions and devices. They also gained new skills in communicating with
      patients and carers about the aims and significance of their research. Meeting
      patients for the first time had a profound impact on some researchers causing
      them to change their professional values. Face-to-face contact seemed
      particularly important to gain a sense of the 'people behind the data', which
      suggests such meetings may result in impacts beyond those typically achieved
      through an exchange of documents. The involvement also influenced one
      researchers' priorities and preferences, in terms of what questions to ask and of
      whom, in their project. Conclusions Researchers learn from an exchange of
      knowledge with patients/ carers, which influences their plans and actions. This
      seems to be one way that involvement subsequently has an impact on research.
      Facilitating this exchange seems important to support mutual learning and to
      enhance the impact on researchers. Future evaluations of involvement might
      benefit from exploring what researchers learnt from patients/carers and how they
      applied their new skills and knowledge.

PMID- 29062546
TI  - Precision Medicine: Where have we reached and where are we headed?

PMID- 29062547
TI  - Myasthaenia Gravis: Clinical management issues before, during and after
      pregnancy.
AB  - Myasthaenia gravis (MG) is an autoimmune neuromuscular disorder which is twice as
      common among women, often presenting in the second and third decades of life.
      Typically, the first trimester of pregnancy and first month postpartum are
      considered high-risk periods for MG exacerbations. During pregnancy, treatment
      for MG is usually individualised, thus improving its management. Plasma exchange
      and immunoglobulin therapies can be safely used to treat severe manifestations of
      the disease or myasthaenic crises. However, thymectomies are not recommended
      because of the delayed beneficial effects and possible risks associated with the
      surgery. Assisted vaginal delivery-either vacuum-assisted or with forceps-may be
      required during labour, although a Caesarean section under epidural anaesthesia
      should be reserved only for standard obstetric indications. Myasthaenic women
      should not be discouraged from attempting to conceive, provided that they seek
      comprehensive counselling and ensure that the disease is under good control
      before the start of the pregnancy.

PMID- 29062548
TI  - Controversies in Odontogenic Tumours: Review.
AB  - Odontogenic tumours are lesions that occur solely within the oral cavity and are
      so named because of their origin from the odontogenic (i.e. tooth-forming)
      apparatus. Odontogenic tumours comprise a variety of lesions ranging from non
      neoplastic tissue proliferations to benign or malignant neoplasms. However,
      controversies exist regarding the pathogenesis, categorisation and clinical and
      histological variations of these tumours. The recent 2017 World Health
      Organization classification of odontogenic tumours included new entities such as
      primordial odontogenic tumours, sclerosing odontogenic carcinomas and odontogenic
      carcinosarcomas, while eliminating several previously included entities like
      keratocystic odontogenic tumours and calcifying cystic odonogenic tumours. The
      aim of the present review article was to discuss controversies and recent
      concepts regarding odontogenic tumours so as to increase understanding of these
      lesions.

PMID- 29062549
TI  - The Roles and Performance of Professional Driving Instructors in Novice Driver
      Education.
AB  - This review article aimed to analyse existing literature regarding the roles and
      performance of professional driving instructors (PDIs) in novice driver education
      (DE). A systematic classification scheme was adopted to analyse identified
      articles to determine the study context of PDIs in novice DE, the competency
      level of PDIs in relation to experienced and learner drivers and the
      contributions of PDIs to the novice driver learning process. A total of 14
      original research articles were identified, with no systematic reviews or meta
      analyses available. Overall, all of the articles were found to be inadequate in
      providing an in-depth understanding of the roles and performance of PDIs in
      novice DE. There is an urgent need to improve current understanding of the roles
      of PDIs in novice DE and to work towards an internationally recognised PDI
      management approach.

PMID- 29062550
TI  - First Cytogenetic Profile of Omani Patients with de novo Myelodysplastic
      Syndromes: Comparison with data from Asia, Africa, Europe and North and South
      America.
AB  - Clonal cytogenetic abnormalities have been reported among 30-80% of patients with
      myelodysplastic syndromes (MDS); however, 20-70% of patients with MDS show a
      normal karyotype that may nevertheless harbour a cryptic genetic alteration.
      Earlier reports have suggested that the distribution of specific chromosomal
      aberrations varies among Western and Asian countries, with geographical and
      ethnic differences in the frequency of specific chromosomal aberrations. This
      article compared the cytogenetic data of 36 adult Omani patients with MDS to
      previously reported data from other populations. Differences were noted between
      the percentages of clonal aberrations and the median age of Omani subjects at
      presentation in comparison to individuals of different ethnicities and from
      various geographical locations. To the best of the authors' knowledge, this is
      the first report to describe the cytogenetic data of patients with MDS from Oman.

PMID- 29062551
TI  - In Vitro Cysteine Reactivates Organophosphate Insecticide Dichlorvos-Inhibited
      Human Cholinesterases.
AB  - OBJECTIVES: Organophosphate (OP) pesticides inhibit both red blood cell (RBC) and
      plasma cholinesterases (ChEs). Oximes, especially pralidoxime (2-PAM), are widely
      used as antidotes to treat OP poisoning. In addition, N-acetylcysteine (NAC) is
      sometimes used as an adjuvant antidote. The current study aimed to assess the
      feasibility of using NAC as a single therapeutic agent for OP poisoning in
      comparison to in vitro 2-PAM. METHODS: This study was carried out at the Razi
      Drug Research Center of Iran University of Medical Sciences, Tehran, Iran,
      between April and September 2014. A total of 22 healthy human subjects were
      recruited and 8 mL citrated blood samples were drawn from each subject.
      Dichlorvos-inhibited blood samples were separately exposed to low and high doses
      (final concentrations of 300 and 600 MUmol.L-1, respectively) of 2-PAM, NAC and
      cysteine. Plasma and RBCs were then separated by centrifugation and their ChE
      activity was measured using spectrophotometry. RESULTS: Although cysteine-and not
      NAC-increased the ChE activity of both plasma and RBCs over those of dichlorvos,
      it did not increase them over those of a high dose of 2-PAM. CONCLUSION: These
      results suggest that the direct reactions of 2-PAM and cysteine with dichlorvos
      and the reactivation of phosphorylated ChEs occurr via an associative stepwise
      addition-elimination process. High therapeutic blood concentrations of cysteine
      are needed for the elevation of ChE activity in plasma and RBCs; however, both
      this agent and NAC may still be effective in the reactivation of plasma and RBC
      ChEs.

PMID- 29062552
TI  - Trends and Outcomes of Non-Small-Cell Lung Cancer in Omani Patients: Experience
      at a university hospital.
AB  - OBJECTIVES: The incidence of lung cancer in Oman has shown a gradual but
      definitive increase since 2002. This study aimed to evaluate the demographic and
      epidemiological characteristics and survival outcomes of patients with non-small
      cell lung cancer (NSCLC) at a university hospital in Oman. METHODS: This study
      was conducted from January to June 2016. A retrospective analysis was performed
      of consecutive patients diagnosed with NSCLC presenting to the Sultan Qaboos
      University Hospital (SQUH) in Muscat, Oman, between March 2000 and December 2015.
      Clinical features at presentation and prognostic and predictive markers were
      reviewed. Kaplan-Meir estimates were used to determine relapse-free survival,
      progression-free survival (PFS) and overall survival (OS). RESULTS: A total of
      104 patients presented to SQUH during the study period. The median age at
      diagnosis was 64 years. Overall, 62 patients (59.6%) had adenocarcinomas. Only 12
      patients (11.5%) presented in the early stages (I or II) of the disease and the
      majority of patients had an Eastern Cooperative Oncology Group performance status
      of 1 (27.9%) or 2 (26.0%). The prevalence of epidermal growth factor receptor
      mutations was 27.9%. The median PFS for patients with advanced disease (stages
      III or IV) was five months and the median OS for all patients was seven months.
      After five years, 50.0%, 60.0%, 10.0% and 8.0% of patients with disease stages I,
      II, III and IV, respectively, were alive. CONCLUSION: Patients with NSCLC in Oman
      were found to present at an advanced stage. However, patient outcomes were
      similar to those reported in the USA.

PMID- 29062553
TI  - Impact of Educational Activities in Reducing Pre-Analytical Laboratory Errors: A
      quality initiative.
AB  - OBJECTIVES: Pre-analytic errors during diagnostic laboratory investigations can
      lead to increased patient morbidity and mortality. This study aimed to ascertain
      the effect of educational nursing activities on the incidence of pre-analytical
      errors resulting in non-conforming blood samples. METHODS: This study was
      conducted between January 2008 and December 2015. All specimens received at the
      Haematology Laboratory of the Sultan Qaboos University Hospital, Muscat, Oman,
      during this period were prospectively collected and analysed. Similar data from
      2007 were collected retrospectively and used as a baseline for comparison. Non
      conforming samples were defined as either clotted samples, haemolysed samples,
      use of the wrong anticoagulant, insufficient quantities of blood collected,
      incorrect/lack of labelling on a sample or lack of delivery of a sample in spite
      of a sample request. From 2008 onwards, multiple educational training activities
      directed at the hospital nursing staff and nursing students primarily responsible
      for blood collection were implemented on a regular basis. RESULTS: After
      initiating corrective measures in 2008, a progressive reduction in the percentage
      of non-conforming samples was observed from 2009 onwards. Despite a 127.84%
      increase in the total number of specimens received, there was a significant
      reduction in non-conforming samples from 0.29% in 2007 to 0.07% in 2015,
      resulting in an improvement of 75.86% (P <0.050). In particular, specimen
      identification errors decreased by 0.056%, with a 96.55% improvement. CONCLUSION:
      Targeted educational activities directed primarily towards hospital nursing staff
      had a positive impact on the quality of laboratory specimens by significantly
      reducing pre-analytical errors.

PMID- 29062554
TI  - Effectiveness of Prophylactic Cervical Cerclage in Prolonging Higher-Order
      Multiple Pregnancies.
AB  - OBJECTIVES: This study aimed to assess the value of prophylactic cervical
      cerclage in prolonging higher-order multiple pregnancies. METHODS: This
      retrospective study included all women with higher-order multiple pregnancies
      beyond 24 gestational weeks treated at the King Abdullah University Hospital in
      Irbid, Jordan, and King Fahad Medical City in Riyadh, Saudi Arabia, between
      February 2014 and January 2015. Selected maternal characteristics and obstetric
      outcomes were compared between women who received prophylactic cervical cerclage
      and those who did not. RESULTS: A total of 146 women with higher-order multiple
      pregnancies were included in the study; of these, 94 (64.4%) underwent a
      prophylactic cervical cerclage insertion procedure and 52 (35.6%) women did not.
      No significant difference was found between the two groups with regards to
      maternal age, parity or number of fetuses. However, the mean gestational age at
      delivery was significantly higher for women without compared to those with
      prophylactic cervical cerclage (32.9 weeks versus 31.7 weeks) according to both
      univariate and multivariate analyses (P = 0.013 and 0.046, respectively).
      Additionally, 40.4% of women without and 14.9% of women with prophylactic
      cervical cerclage gave birth after 34 gestational weeks (P = 0.003). CONCLUSION:
      Overall, prophylactic cervical cerclage was not associated with prolongation of
      the pregnancy among women with higher-order multiple pregnancies in the current
      study.

PMID- 29062555
TI  - Synoptic Versus Narrative Reporting of Prostate Biopsies at a Tertiary Healthcare
      Institution: Challenges, successes and expectations.
AB  - OBJECTIVES: Cancer pathology reports are expected to contain all information
      required for patient management and disease surveillance. Moreover, reports for
      patients with prostate cancer have become increasingly complex with the addition
      of more pathological details. This study aimed to compare narrative and synoptic
      prostate cancer reports for core needle biopsies received at a tertiary hospital
      in Nigeria in order to determine which form was most complete according to
      international standards. METHODS: This study was conducted from January 2010 to
      December 2015 at the Lagos University Teaching Hospital, Lagos, Nigeria. All
      malignant prostate cancer histopathology reports received during this period were
      analysed for the presence of important clinicopathological parameters, including
      the numbers of cores taken and those involved by the tumour, percentage of tumour
      involvement, Gleason score and the presence of high-grade prostatic
      intraepithelial neoplasms (HGPINs) and perineural and lymphovascular invasion.
      RESULTS: A total of 83 reports were reviewed, of which 27 were in narrative and
      56 in synoptic format. The documentation of clinicopathological characteristics
      in narrative reports was significantly incomplete compared to synoptic reports in
      recording the number of cores (33.3% versus 96.4%), number of cores involved by
      the tumour (11.1% versus 94.6%), percentage of cores involved by the tumour (3.7%
      versus 100.0%) and the presence of HGPINs (7.4% versus 100.0%) and perineural
      (59.3% versus 98.2%) and lymphovascular (48.1% versus 100.0%) invasion (P <0.001
      each). CONCLUSION: Synoptic reports of malignant prostate cancer biopsies
      received at the Lagos University Teaching Hospital were found to contain more
      complete information than narrative reports.

PMID- 29062556
TI  - Neurology Research in Saudi Arabia: Urgent call for action.
AB  - OBJECTIVES: Research activities in Saudi Arabia are promoted at the governmental
      and institutional levels. However, the output and quality of research conducted
      in the field of neurology has not yet been measured quantitatively. This study
      therefore aimed to analyse neurology-related publications from Saudi Arabia.
      METHODS: This study was conducted in January 2016. A systematic search using the
      PubMed(r) search engine (National Library of Medicine, Bethesda, Maryland, USA)
      was conducted to identify all neurology-related articles published from Saudi
      Arabia between January 1996 and December 2015. RESULTS: A total of 1,292
      neurology-related publications were identified. Neurology research increased
      linearly with time, with most publications originating from Riyadh (67%) and the
      university sector (~47%). However, most neurology-related articles were published
      in journals which had an impact factor of <1 (55%). CONCLUSION: Neurology
      research in Saudi Arabia has increased substantially over the last 20 years.
      However, as most articles were published in low-impact journals, the quality of
      research remains inadequate and should be improved. It is important that an
      official research culture be established in both governmental and private
      universities as well as colleges and health institutions in Saudi Arabia. The
      formation of clinical academic departments staffed by research experts is
      recommended to ensure the quality of neurology research output.

PMID- 29062557
TI  - Relationship Between Medication Adherence and Health Beliefs Among Patients with
      Hypertension in Oman: Pilot study.
AB  - OBJECTIVES: The prevalence of hypertension (HTN) in Oman is alarmingly high and
      patient adherence to antihypertensive medications is inadequate. This study aimed
      to assess the relationship between medication adherence and health beliefs among
      Omani patients with HTN. METHODS: This descriptive cross-sectional pilot study
      was conducted in December 2015 and included 45 patients with HTN recruited from
      four primary health centres in Al Dakhiliyah and Muscat governorates, Oman.
      Medication adherence and health beliefs were assessed using the Morisky
      Medication Adherence Scale (MMAS), Beliefs about Medicines Questionnaire, Brief
      Illness Perception Questionnaire and the revised Medication Adherence Self
      Efficacy Scale. RESULTS: The mean MMAS score was 5.3 +/- 2.0, with 48.9% of
      patients reporting high adherence. Higher self-efficacy and stronger beliefs
      regarding medication necessity were significantly related to adherence (P = 0.012
      and 0.028, respectively). CONCLUSION: The findings of this pilot study emphasise
      the role of health beliefs with regards to Omani patients' adherence to
      antihypertensive medications.

PMID- 29062559
TI  - Secondary Adrenal Insufficiency Due to the Co-Administration of Ritonavir and
      Inhaled Fluticasone Propionate: Case report.
AB  - Ritonavir is a powerful inhibitor of the cytochrome P450 3A4 (CYP3A4) isoenzyme.
      It is used as a pharmaceutical enhancer in the management of HIV-positive
      patients. However, when co-administered with other drugs that are metabolised via
      the CYP3A4 pathway, ritonavir can potentially cause serious drug-drug
      interactions. Inhaled fluticasone propionate, which is used to treat asthma and
      chronic obstructive airway disease, is particularly prone to such interactions
      due to its physiological attributes. We report a HIV-positive 48-year-old male
      patient who presented to Al Nahdha Hospital, Muscat, Oman, in 2012 with weight
      loss, generalised weakness and fatigue and diagnosed with secondary adrenal
      insufficiency as a result of concomitant ritonavir and inhaled fluticasone.

PMID- 29062558
TI  - Bilateral Diaphragmatic Paralysis Following Paediatric Cardiac Surgery:
      Experience of four cases at the Royal Hospital, Muscat, Oman.
AB  - Bilateral diaphragmatic paralysis (BDP) is a rare complication of paediatric
      cardiac surgery. We report four children who developed BDP following cardiac
      surgery who were managed at the Royal Hospital, Muscat, Oman, between 2009 and
      2014. All four children suffered severe respiratory distress soon after
      extubation and required re-intubation within two hours. In addition, all of the
      children underwent a tracheostomy as an interim method for ventilation. The four
      children were successfully weaned from positive pressure ventilation following
      the functional recovery of at least one side of the diaphragm.

PMID- 29062560
TI  - Use of a Minimally Invasive Cardiac Output Monitor to Optimise Haemodynamics in a
      Patient with Mitral Valve Disease Undergoing Cerebrovascular Surgery.
AB  - Patients with mitral valve disease undergoing cerebrovascular surgery face
      increased inherent risks due to their associated cardiac comorbidities. As such,
      the anaesthetic management of such patients is distinctly challenging.
      Simultaneous consideration of both the cerebrovascular and underlying cardiac
      conditions determines key anaesthetic issues, as fluids and vasopressors or
      inotropes need to be titrated according to haemodynamic variables in order to
      optimise cerebral blood flow without compromising cardiac function. We report a
      45-year-old female patient with mild mitral stenosis and moderate-to-severe
      mitral regurgitation who presented to the Khoula Hospital, Muscat, Oman, in 2016
      following a ruptured anterior communicating artery aneurysm requiring urgent
      surgical intervention. As highlighted in this case, the VolumeView EV1000TM
      (Edwards Lifesciences, Irvine, California, USA) system is a minimially invasive
      haemodynamic monitor that can help immensely in the perioperative management of
      such patients.

PMID- 29062561
TI  - Transposition of the Great Arteries and Coarctation of the Aorta in an Infant
      Presenting with Bronchiolitis: An incidental finding.
AB  - The transposition of the great arteries (TGA) is a complex congenital heart
      disease which usually presents as cyanosis in neonates with limited mixing
      between the systemic and pulmonary circulatory systems. A delayed diagnosis of
      TGA can lead to ventricular failure. We report a six-week-old infant who was
      admitted to the paediatric Intensive Care Unit of the Royal Hospital, Muscat,
      Oman, in 2016 for bronchiolitis. During admission, she was incidentally diagnosed
      with TGA and coarctation of the aorta. Postnatal screening, including the use of
      pulse oximetry, plays a significant role in avoiding a late diagnosis of TGA;
      however, this screening tool is not widely used in Oman. Moreover, the common
      practice of applying a pulse oximetry probe only to the foot may have been
      limited in the current case due to the reverse differential saturation between
      the upper and lower limbs caused by this particular combination of lesions.

PMID- 29062562
TI  - Anomalous Origin of the Right Coronary Artery from the Left Coronary Sinus: Case
      report.
AB  - The anomalous origin of the right coronary artery from the left coronary sinus is
      a rare congenital disorder and can often result in sudden death upon initial
      presentation. We report a 19-year-old male patient who was referred to the Sultan
      Qaboos University Hospital, Muscat, Oman, in 2015 with multiple episodes of
      exertional angina. He was diagnosed as having an anomalous right coronary artery
      arising from the left coronary sinus following an intraoperative transesophageal
      echocardiogram. An unroofing ostioplasty of the anomalous right coronary artery
      was successful. Details of the surgical management of this anomaly are discussed.

PMID- 29062563
TI  - Segmental Spinal Muscular Atrophy Localised to the Lower Limbs: First case from
      Oman.
AB  - Spinal muscular atrophy (SMA) is a genetic lower motor neuron disease. It usually
      involves all of the skeletal muscles innervated by the anterior horn cells of the
      spinal cord. In rare cases, there is also localised involvement of the spinal
      cord. We report a 10-year-old boy who presented to the Sultan Qaboos University
      Hospital, Muscat, Oman, in 2015 with muscle weakness restricted to the lower
      limbs. The presence of a homozygous deletion within the survival of motor neuron
      1 gene confirmed the diagnosis of SMA. To the best of the authors' knowledge,
      this is the first report of an Omani patient with segmental SMA involving only
      the lower limbs. Treatment for this rare and relatively benign form of SMA is
      symptomatic and includes physiotherapy.

PMID- 29062564
TI  - Bacille Calmette-Guerin Vaccine-Induced Tuberculous Hip Osteomyelitis in an
      Infant: Case report.
AB  - To this day, tuberculosis (TB) continues to pose a significant global health
      burden. The World Health Organization's Expanded Programme on Immunization (EPI)
      recommends the bacille Calmette-Guerin (BCG) vaccine for infants to protect
      against the haematogenous spread of primary TB and other more severe types of TB
      infection. We report an eight-month-old boy who presented to the Armed Forces
      Hospital, Muscat, Oman, in 2015 with a one-month history of intermittent fever
      associated with a limited range of motion in the right hip area. He was up-to
      date with his EPI vaccinations and had no history of exposure to individuals with
      TB infections. He was initially treated for bacterial septic arthritis; however,
      a GeneXpert TB assay revealed the presence of Mycobacterium tuberculosis, BCG
      strain. To the best of the authors' knowledge, this is the first documented case
      from Oman of a child with TB hip osteomyelitis due to a BCG vaccination.

PMID- 29062565
TI  - Unusual Case of an Intracranial Aneurysm Misdiagnosed as Focal Basal Meningitis.

PMID- 29062566
TI  - Subamniotic Haematoma Associated with an Uneventful Labour.

PMID- 29062567
TI  - A Rare Case of Coexisting Superior Mesenteric Artery Syndrome and Nutcracker
      Phenomenon.

PMID- 29062568
TI  - Umbilical Endometriosis.

PMID- 29062569
TI  - Atrophoderma of Pasini and Pierini.

PMID- 29062570
TI  - Multiple Clustered Dermatofibromas Following Ustekinumab Treatment for Psoriasis
      Vulgaris.

PMID- 29062572
TI  - A novel minimum cost maximum power algorithm for future smart home energy
      management.
AB  - With the latest development of smart grid technology, the energy management
      system can be efficiently implemented at consumer premises. In this paper, an
      energy management system with wireless communication and smart meter are designed
      for scheduling the electric home appliances efficiently with an aim of reducing
      the cost and peak demand. For an efficient scheduling scheme, the appliances are
      classified into two types: uninterruptible and interruptible appliances. The
      problem formulation was constructed based on the practical constraints that make
      the proposed algorithm cope up with the real-time situation. The formulated
      problem was identified as Mixed Integer Linear Programming (MILP) problem, so
      this problem was solved by a step-wise approach. This paper proposes a novel
      Minimum Cost Maximum Power (MCMP) algorithm to solve the formulated problem. The
      proposed algorithm was simulated with input data available in the existing
      method. For validating the proposed MCMP algorithm, results were compared with
      the existing method. The compared results prove that the proposed algorithm
      efficiently reduces the consumer electricity consumption cost and peak demand to
      optimum level with 100% task completion without sacrificing the consumer comfort.

PMID- 29062571
TI  - Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues Ferroportin and
      Ferritin Expression in Obese Mice.
AB  - Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron
      levels by increasing internalization of ferroportin-a transmembrane protein
      facilitating egress of cellular iron. Chronic low-grade inflammatory states, such
      as obesity, have been shown to increase oxidative stress and enhance hepcidin
      secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO) is a stress
      response system which reduces oxidative stress. We investigated the effects of HO
      1 induction on hepatic hepcidin levels and on iron homeostasis in hepatic tissues
      from lean and obese mice. Obese mice exhibited hyperglycemia (p < 0.05);
      increased levels of proinflammatory cytokines (MCP-1, IL-6, p < 0.05); oxidative
      stress (p < 0.05); and increased hepatic hepcidin levels (p < 0.05). Enhancement
      of hepcidin was reflected in the reduced expression of ferroportin in obese mice
      (p < 0.05). However, this effect is accompanied by a significant decline in
      ferritin expression. Additionally, there are reduced insulin receptor
      phosphorylation and attenuation of metabolic regulators pAMPK, pAKT, and pLKB1.
      Cobalt protoporphyrin- (CoPP-) induced HO-1 upregulation in obese mice reversed
      these alterations (p < 0.05), while attenuating hepatic hepcidin levels. These
      effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor
      of HO (SnMP) (p < 0.05). Our results highlight a modulatory effect of HO on iron
      homeostasis mediated through the suppression of hepatic hepcidin.

PMID- 29062573
TI  - Increased susceptibility of post-weaning rats on high-fat diet to metabolic
      syndrome.
AB  - The present study aimed to examine the effects of the types of high-calorie diets
      (high-fat and high-fat-high-sucrose diets) and two different developmental stages
      (post-weaning and young adult) on the induction of metabolic syndrome. Male, post
      weaning and adult (3- and 8-week old, respectively) Sprague Dawley rats were
      given control, high-fat (60% kcal), and high-fat-high-sucrose (60% kcal fat + 30%
      sucrose water) diets for eight weeks (n = 6 to 7 per group). Physical,
      biochemical, and transcriptional changes as well as liver histology were noted.
      Post-weaning rats had higher weight gain, abdominal fat mass, fasting glucose,
      high density lipoprotein cholesterol, faster hypertension onset, but lower
      circulating advanced glycation end products compared to adult rats. This is
      accompanied by upregulation of peroxisome proliferator-activated receptor (PPAR)
      alpha and gamma in the liver and receptor for advanced glycation end products
      (RAGE) in the visceral adipose tissue. Post-weaning rats on high-fat diet
      manifested all phenotypes of metabolic syndrome and increased hepatic steatosis,
      which are linked to increased hepatic and adipocyte PPARgamma expression. Adult
      rats on high-fat-high-sucrose diet merely became obese and hypertensive within
      the same treatment duration. Thus, it is more effective and less time-consuming
      to induce metabolic syndrome in male post-weaning rats with high-fat diet
      compared to young adult rats. As male rats were selectively included into the
      study, the results may not be generalisable to all post-weaning rats and further
      investigation on female rats is required.

PMID- 29062574
TI  - Analysis of Adverse Events during Intrahospital Transportation of Critically Ill
      Patients.
AB  - PURPOSE: To describe adverse events occurring during intrahospital transportation
      of adult patients hospitalized in an Intensive Care Unit (ICU) and to evaluate
      the association with morbidity and mortality. METHOD: Prospective cohort study
      from July 2014 to July 2015. Data collection comprised clinical data, prognostic
      scores, length of stay, and outcome at hospital discharge. Data was collected on
      transport and adverse events. Adverse events were classified according to the
      World Health Organization following the degree of damage. The level of
      significance was set at 5%. RESULTS: A total of 293 patients were analyzed with
      follow-up of 143 patient transportations and records of 86 adverse events. Of
      these events, 44.1% were related to physiological alterations, 23.5% due to
      equipment failure, 19.7% due to team failure, and 12.7% due to delays. Half of
      the events were classified as moderate. The mean time of hospital stay of the
      group with adverse events was higher compared to patients without adverse events
      (31.4 versus 16.6 days, resp., p < 0.001). CONCLUSIONS: Physiological alterations
      were the most frequently encountered events, followed by equipment and team
      failures. The degree of damage associated with adverse events was classified as
      moderate and associated with an increase in the length of hospital stay.

PMID- 29062575
TI  - Novel Combined Training Approach Improves Sleep Quality but Does Not Change Body
      Composition in Healthy Elderly Women: A Preliminary Study.
AB  - The aim of this study was to investigate the effects of a novel combined training
      protocol on sleep quality and body composition of healthy elderly women. The
      study sample consisted of 8 sedentary elderly individuals with mean (+/-SD) of 67
      (+/-8) years of age, 96.0 (+/-7.8) mg/dL fasting blood glucose, 94.4 (+/-36.1)
      mg/dL triglycerides, 179.1 (+/-22.4) mg/dL total cholesterol, 57.2 (+/-15.7)
      mg/dL high-density lipoprotein (HDL), 103.1 (+/-25.2) mg/dL low-density
      lipoprotein (LDL), 125.3 (+/-8.4) mmHg systolic blood pressure, and 72.6 (+/
      10.1) mmHg diastolic blood pressure. The training protocol consisted of
      resistance training exercises (approximately 18-minute duration) combined with
      aerobic exercises (approximately 26-minute duration), performed interspersed in
      the same session, for 8 weeks (3 times a week), with a 24-hour interval rest
      between each session. Continuous variables were expressed as the mean (+/
      standard deviation) and the paired sample t-test compares baseline with final
      measurement. The results showed a significant improvement (p = 0.01) in quality
      of sleep (4.9 +/- 1.5 versus 3.8 +/- 1.8 for total PSQI index) without body
      significant improvements in the fat-free mass (59.9 +/- 4.0 versus 60.5 +/- 4.4;
      p = 0.20) and fat mass (40.1 +/- 4.0 versus 39.5 +/- 4.4; p = 0.20) in healthy
      elderly women. In this sense, the novel combined training proposed may be an
      effective alternative or adjunct to present therapies aimed at improving the
      sleep quality in this population.

PMID- 29062576
TI  - Does the Somatosensory Temporal Discrimination Threshold Change over Time in
      Focal Dystonia?
AB  - BACKGROUND: The somatosensory temporal discrimination threshold (STDT) is defined
      as the shortest interval at which an individual recognizes two stimuli as
      asynchronous. Some evidence suggests that STDT depends on cortical inhibitory
      interneurons in the basal ganglia and in primary somatosensory cortex. Several
      studies have reported that the STDT in patients with dystonia is abnormal. No
      longitudinal studies have yet investigated whether STDT values in different forms
      of focal dystonia change during the course of the disease. METHODS: We designed a
      follow-up study on 25 patients with dystonia (15 with blepharospasm and 10 with
      cervical dystonia) who were tested twice: upon enrolment and 8 years later. STDT
      values from dystonic patients at the baseline were also compared with those from
      a group of 30 age-matched healthy subjects. RESULTS: Our findings show that the
      abnormally high STDT values observed in patients with focal dystonia remained
      unchanged at the 8-year follow-up assessment whereas disease severity worsened.
      CONCLUSIONS: Our observation that STDT abnormalities in dystonia remain
      unmodified during the course of the disease suggests that the altered activity of
      inhibitory interneurons-either at cortical or at subcortical level-responsible
      for the increased STDT does not deteriorate as the disease progresses.

PMID- 29062577
TI  - Metastatic Sarcomatoid Squamous Cell Carcinoma of the Cervix Presenting with
      Chest Mass.
AB  - BACKGROUND: Sarcomatoid squamous cell carcinoma is a rare and aggressive form of
      cervical cancer. We report a case of metastatic sarcomatoid squamous cell
      carcinoma (SSCC) of cervix that presented with an anterior chest wall mass. CASE:
      A 43-year-old Hispanic female presented with a two-month history of a central
      chest wall mass. The patient's only past medical history was SSCC of the cervix,
      stage IIB, diagnosed two years priorly. She underwent neoadjuvant chemoradiation
      therapy (CRT) with cisplatin followed by radical hysterectomy. Surgical margins
      were positive which led to adjuvant CRT with carboplatin and paclitaxel. PET scan
      4 months after the postoperative treatment was negative for recurrence and
      metastatic disease. On current presentation, the CT chest revealed anterior
      mediastinal destructive soft tissue mass involving sternum, and the biopsy showed
      SSCC. The patient received palliative radiation therapy to her chest with
      improvement in pain and ability to swallow. After discussing the prognosis she
      refused further chemotherapy and decided on hospice care. CONCLUSION: Despite
      good response to first-line therapy, SSCC tends to recur early and does not
      respond to second-line therapy. Radiation therapy seems to be the most effective
      modality for treatment, but randomized controlled trials of therapy are
      impractical.

PMID- 29062578
TI  - Immune Thrombocytopenia in a Child with Neuroblastoma.
AB  - Thrombocytopenia is a frequent finding in patients with solid tumors. It is
      usually caused by bone marrow infiltration or by myelosuppression due to
      anticancer therapy; however immune thrombocytopenia (ITP) associated with solid
      tumors is rare. Neuroblastoma is the most common extracranial solid tumor in
      children. Here we report the case of a two-year-nine-month-old patient with
      adrenal neuroblastoma who presented with ITP. Paraneoplastic ITP was considered
      in the differential diagnosis. Bone marrow infiltration and other causes of
      thrombocytopenia were excluded and the patient was treated with intravenous
      immunoglobulin and tumor resection. Platelet count increased rapidly after
      surgery and complete remission of ITP was achieved.

PMID- 29062579
TI  - Successful Treatment of Hemophagocytic Lymphohistiocytosis Associated with Lupus
      Nephritis by Using Mycophenolate Mofetil.
AB  - An estimated 0.9% to 2.4% of patients with systemic lupus erythematosus (SLE)
      also have hemophagocytic lymphohistiocytosis (HLH). HLH associated with
      autoimmune diseases is often refractory to corticosteroid treatment; thus,
      additional immunosuppressive drugs, such as cyclosporine, cyclophosphamide, or
      tacrolimus, are required. Here, we describe the case of a 44-year-old Japanese
      woman who developed HLH associated with lupus nephritis. Initially, her HLH was
      refractory to treatment with a corticosteroid, tacrolimus, and mizoribine.
      However, alternative treatment with a corticosteroid, mycophenolate mofetil, and
      tacrolimus improved both her HLH and lupus nephritis. This case suggests the
      possibility of mycophenolate mofetil as a key drug for treating HLH associated
      with SLE.

PMID- 29062580
TI  - Hem-o-lok Clips Migration: An Easily Neglected Complication after Laparoscopic
      Biliary Surgery.
AB  - Clip migration into the common bile duct (CBD) is a rare but well-established
      phenomenon of laparoscopic biliary surgery. The mechanism and exact incidence of
      clip migration are both poorly understood. Clip migration into the common bile
      duct can cause recurrent cholangitis and serve as a nidus for stone formation. We
      present a case, a 54-year-old woman, of clip-induced cholangitis resulting from
      surgical clip migration 12 months after laparoscopic cholecystectomy and
      laparoscopic common bile duct exploration (LC+LCBDE) with primary closure.

PMID- 29062581
TI  - Collecting Duct Carcinoma of the Native Kidney in a Renal Transplant Recipient.
AB  - Collecting duct carcinoma (CDC) is a rare and aggressive form of renal cell
      carcinoma (RCC) arising from the epithelium of Bellini's duct. It presents
      earlier in life and has a poorer prognosis than the clear-cell type.
      Historically, immunosuppressed renal transplant patients are more likely to
      develop malignancies than the general population. We report a case of CDC of the
      native kidney in a 59-year-old man who initially underwent kidney transplantation
      five years before the time of presentation. To our knowledge, CDC in the setting
      of renal transplant and long-term immunosuppression has not been previously
      described.

PMID- 29062583
TI  - The End-Diastolic Velocity of Thyroid Arteries Is Strongly Correlated with the
      Peak Systolic Velocity and Gland Volume in Patients with Autoimmune Thyroiditis.
AB  - BACKGROUND: The end-diastolic velocity (EDV) of thyroid arteries reflects
      peripheral blood flow resistance. OBJECTIVE: The aim was to evaluate EDV
      correlations with other Doppler sonography parameters and with clinical and
      biochemical variables in a sample of patients with hypothyroidism caused by
      chronic autoimmune thyroiditis (CAT). METHODS: A sample of 48 CAT hypothyroid
      patients receiving treatment with stable doses of levothyroxine was selected. The
      participants underwent clinical evaluation and measurement of serum thyrotropin
      (TSH), total triiodothyronine (T3), total thyroxine (T4), free T4, thyroid
      peroxidase antibodies (anti-TPO), and antithyroglobulin antibodies (anti-Tg) and
      Doppler sonography. RESULTS: The EDV of the inferior thyroid arteries (ITA-EDV)
      was strongly and positively correlated with the peak systolic velocity of the
      inferior thyroid arteries (ITA-PSV, r = 0.919), thyroid volume (r = 0.711), and
      thyroid visual vascularization pattern (TVP, r = 0.687). There was no correlation
      between ITA-EDV and the clinical variables, hormones, anti-TPO, or anti-Tg.
      CONCLUSION: The strong correlation of ITA-EDV with ITA-PSV, TVP, and volume
      suggests that increased vascularization in CAT may be associated with a reduction
      in thyroid blood flow resistance, possibly due to an angiogenesis-induced
      increase in the total vascular cross-sectional area of the parenchyma.

PMID- 29062582
TI  - Effect of Remote Ischemic Preconditioning on Perioperative Cardiac Events in
      Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis
      of 16 Randomized Trials.
AB  - BACKGROUND: The main objective of this meta-analysis was to investigate whether
      remote ischemic preconditioning (RIPC) reduces cardiac and renal events in
      patients undergoing elective cardiovascular interventions. METHODS AND RESULTS:
      We systematically searched articles published from 2006 to 2016 in PubMed,
      EMBASE, Web of Science, Cochrane Library, and Google Scholar. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used as the effect index for dichotomous
      variables. The standardized mean differences (SMDs) with 95% CIs were calculated
      as the pooled continuous effect. Sixteen RCTs of 2435 patients undergoing
      elective PCI were selected. Compared with control group, RIPC could significantly
      reduce the incidence of perioperative myocardial infarction (OR = 0.64; 95% CI:
      0.48-0.86; P = 0.003) and acute kidney injury (OR = 0.56; 95% CI: 0.322-0.99; P =
      0.049). Metaregression analysis showed that the reduction of PMI by RIPC was
      enhanced for CAD patients with multivessel disease (coef.: -0.05 [-0.09; -0.01],
      P = 0.022). There were no differences in the changes of cTnI (P = 0.934) and CRP
      (P = 0.075) in two groups. CONCLUSION: Our meta-analysis of RCTs demonstrated
      that RIPC can provide cardiac and renal protection for patients undergoing
      elective PCI, while no beneficial effect on reducing the levels of cTnI and CRP
      after PCI was reported.

PMID- 29062584
TI  - Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with
      Swallowed Topical Steroids.
AB  - Swallowed topical steroids (STS) are the only effective pharmacological therapy
      for eosinophilic esophagitis (EoE). Thus far, studies of small populations of EoE
      patients have reported conflicting results in relation to adrenal insufficiency
      (AI). We sought to measure AI in a clinical setting in children taking STS for
      EoE. We performed a quality improvement study of pediatric EoE patients seen in a
      multidisciplinary clinic, who were treated with STS for at least 3 months. Two
      hundred twenty-five patients completed questionnaires to assess for signs of AI.
      All patients were requested to have fasting morning cortisol levels completed and
      if abnormal (<5 MUg/dL or 139 nmol/L) twice, endocrinology consultation, and low
      dose adrenocorticotropic hormone stimulation test were performed. A peak
      stimulated cortisol level of <18 MUg/dL or 500 nmol/L was diagnostic of AI. Five
      of 106 STS-treated EoE patients who had morning cortisol levels drawn had AI. All
      5 of these patients had asthma and were on additional topical steroid treatments.
      The number of steroid modalities and dose of steroid were not significant risk
      factors. Despite this low percentage, the life-threatening potential of AI
      warrants patient screening, as patients with iatrogenic AI are typically
      asymptomatic until an emergency triggers adrenal crisis. Further multicenter
      studies are needed to better define the risk attributable to STS alone,
      particularly in patients receiving combined steroid modalities.

PMID- 29062585
TI  - Fetal Tobacco Smoke Exposure in the Third Trimester of Pregnancy Is Associated
      with Atopic Eczema/Dermatitis Syndrome in Infancy.
AB  - The manifestation of atopic dermatitis (AD) is initially nonatopic eczema in
      early infancy; the manifestations subsequently change in age-specific stages.
      Since allergen-specific T-helper 2 cells appear in the fetus primarily after the
      third trimester of pregnancy and rapidly mature during the first 6 months of
      life, different timings of tobacco smoke exposure may have different effects on
      AD. In this study, we investigated whether the timing of fetal or/and infantile
      tobacco smoke exposure affects the cumulative incidence of atopic
      eczema/dermatitis syndrome (AEDS) in infants in Japan. This cross-sectional study
      enrolled 1,177 parent-infant pairs, in which the infants were >6 months old.
      Parental allergic history, number of older siblings, physician-diagnosed AEDS and
      food allergy (FA), and the perinatal fetal and/or infantile tobacco smoke
      exposure timing after 28 weeks gestation and during the first 6 months of life
      were assessed using self-completed questionnaires. Fetal tobacco smoke exposure
      after 28 weeks gestation was significantly associated with higher cumulative
      incidence of AEDS in exposed infants than in unexposed infants: AEDS in all
      infants, 41.4% versus 34.0% (Chi-squared, P = 0.020; adjusted odds ratio, 5.21;
      95% confidence interval, 1.08-25.15); AEDS in those without parental allergic
      history, 38.0% versus 26.6% (Chi-squared, P = 0.024). Postnatal infantile tobacco
      smoke exposure timing was not significantly associated with cumulative incidence
      of AEDS. No significant associations were observed between any tobacco smoke
      exposure timings and the cumulative incidence of FA. Fetal tobacco smoke exposure
      during the third trimester of pregnancy was positively associated with AEDS in
      infancy and might induce epigenetic changes in the fetal allergen-specific immune
      responses.

PMID- 29062586
TI  - "Cut and Sew" Transformations via Transition-Metal-Catalyzed Carbon-Carbon Bond
      Activation.
AB  - The transition metal-catalyzed "cut and sew" transformation has recently emerged
      as a useful strategy for preparing complex molecular structures. After oxidative
      addition of a transition metal into a carbon-carbon bond, the resulting two
      carbon termini can be both functionalized in one step via the following migratory
      insertion and reductive elimination with unsaturated units, such as alkenes,
      alkynes, allenes, CO and polar multiple bonds. Three- or four-membered rings are
      often employed as reaction partners due to their high ring strains. The
      participation of non-strained structures generally relies on cleavage of a polar
      carbon-CN bond or assistance of a directing group.

PMID- 29062587
TI  - One-week glucose control via zero-order release kinetics from an injectable depot
      of glucagon-like peptide-1 fused to a thermosensitive biopolymer.
AB  - Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment
      strategy for type 2 diabetes because of pleiotropic effects, including the
      regulation of islet hormones and the induction of satiety. However, the native
      ligand for the GLP1 receptor has a short half-live owing to enzymatic
      inactivation and rapid clearance. Here, we show that a subcutaneous depot formed
      after a single injection of GLP1 recombinantly fused to a thermosensitive elastin
      like polypeptide results in zero-order release kinetics and circulation times of
      up to 10 days in mice and 17 days in monkeys. The optimized pharmacokinetics
      leads to 10 days of glycemic control in three different mouse models of diabetes,
      as well as to the reduction of glycosylated hemoglobin levels and weight gain in
      ob/ob mice treated once weekly for 8 weeks. Our results suggest that the
      optimized GLP1 formulation could enhance therapeutic outcomes by eliminating peak
      and-valley pharmacokinetics and improving overall safety and tolerability. The
      design principles that we established should be broadly applicable for improving
      the pharmacological performance of other peptide and protein therapeutics.

PMID- 29062588
TI  - TLR4 Ligands Selectively Synergize to Induce Expression of IL-8.
AB  - Objective: Dysfunctional remodeling of the extracellular matrix contributes to
      the formation of TLR-dependent feed forward loops that drive chronic
      inflammation. We have previously shown that two Type III domains of Fibronectin,
      FnEDA and FnIII-1c, cooperate to induce the synergistic release of interleukin 8
      (IL-8) from dermal fibroblasts. We now identify steps in the TLR4 pathway where
      synergy can be demonstrated as well as additional kinases functioning in
      fibronectin activation of TLR4 signaling. We also evaluate the ligand and cell
      type specificity of this synergistic response. Approach: FnEDA, FnIII-1c, and
      lipopolysaccharide (LPS)-induced genes in fibroblasts were analyzed by a
      quantitative reverse transcription-polymerase chain reaction (qPCR) and protein
      was measured by an enzyme-linked immunosorbent assay (ELISA). Kinases functioning
      in gene expression were identified by using specific inhibitors. Activated TLR4
      dependent effector molecules were identified by cell fractionation and Western
      blot and quantified by image analysis. Results: The addition of FnEDA and FnIII
      1c to dermal fibroblasts resulted in a synergistic increase in the expression of
      IL-8, tumor necrosis factor alpha (TNF-alpha), and vascular cell adhesion
      molecule (VCAM-1). Synergy between these domains was detected at the level of
      nuclear factor kappa-light chain enhancer of activated B cells (NF-kappaB) and
      inhibitor of kappa B kinase (IKK) activation. Induction of IL-8 by fibronectin
      ligands was partially attenuated in the presence of inhibitors to either
      epidermal growth factor receptor or Src kinases. FnIII-1c also synergized with
      LPS to induce IL-8 in dermal fibroblasts, whereas the combined effect of FnEDA
      and LPS on IL-8 synthesis was additive. In contrast, synergistic responses to
      these ligands were not observed in THP-1 monocytic cells. Innovation: The data
      suggest that chronic inflammation may be driven by matrix- and pathogen-derived
      TLR4 ligands that work in synergy to promote an exuberant innate response.
      Conclusion: The data suggest that the molecular mechanism underlying synergistic
      responses to TLR4 ligands lies upstream of IKK activation, likely in the
      molecular composition of the TLR4 receptor complex that assembles in response to
      each ligand. In addition, synergistic responses to TLR4 activation may be both
      cell-type and ligand specific.

PMID- 29062589
TI  - Integration of Canonical and Noncanonical Pathways in TLR4 Signaling: Complex
      Regulation of the Wound Repair Program.
AB  - Significance: Chronic inflammation and maladaptive repair contribute to the
      development of fibrosis that negatively impacts quality of life and organ
      function. The toll-like receptor (TLR) system is a critical node in the tissue
      response to both exogenous (pathogen-associated) and endogenous (damage
      associated) molecular pattern factors (PAMPs and DAMPs, respectively). The
      development of novel TLR ligand-, pathway-, and/or target gene-specific
      therapeutics may have clinical utility in the management of the exuberant
      inflammatory/fibrotic tissue response to injury without compromising the host
      defense to pathogens. Recent Advances: DAMP ligands, released upon wounding, and
      microbial-derived PAMPs interact with several TLRs, and their various coreceptor
      partners, engaging downstream pathways that include Src family kinases, the
      epidermal growth factor receptor, integrins and the tumor suppressor phosphatase
      and tensin homolog (PTEN). Toll-like receptor 4 (TLR4) activation enhances
      cellular responses to the potent profibrotic cytokine transforming growth factor
      beta1 (TGF-beta1) by attenuating the expression of receptors that inhibit TGF
      beta1 signaling. Critical Issues: Common as well as unique pathways may be
      activated by PAMP and DAMP ligands that bind to the repertoire of TLRs on various
      cell types. Dissecting mechanisms underlying ligand-dependent engagement of this
      complex, highly interactive, network will provide for adaptation of new and
      focused therapies directed to the regulation of pathologically significant
      profibrotic genes. Inherent in this diversity are therapeutic opportunities to
      modulate the pathophysiologic consequences of persistent TLR signaling. The
      recently identified involvement of receptor and nonreceptor kinase pathways in
      TLR signaling may present novel opportunities for pharmacologic intervention.
      Future Directions: Clarifying the identity and function of DAMP-activated TLR
      complexes or ligand-binding partners, as well as their engaged downstream
      effectors and target genes, are key factors in the eventual design of pathway
      specific treatment modalities. Such approaches may be tailored to address the
      spectrum of TLR-initiated pathologies (including localized and persistent
      inflammation, maladaptive repair/fibrosis) and, perhaps, even titrated to achieve
      patient-unique beneficial clinical outcomes.

PMID- 29062590
TI  - Toll-Like Receptor Signaling in Burn Wound Healing and Scarring.
AB  - Significance: Damage-associated molecular patterns (DAMPs) and pathogen
      associated molecular patterns (PAMPs) emanate from burn-injured tissue and enter
      systemic circulation. Locally and systemically, they activate pattern-recognition
      receptors, including toll-like receptors (TLRs), to stimulate cytokine secretion,
      which in the severest burns typically results in extreme systemic cytokine
      levels, a dysfunctioning immune system, infection, impaired healing, and
      excessive scarring. This system-wide disruption of homeostasis can advance to
      life-threatening, multiorgan dysfunction syndrome. Knowledge of DAMP- and PAMP
      TLR signaling may lead to treatments that ameliorate local and systemic
      inflammation and reduce scarring and other burn injury sequela. Recent Advances:
      Many PAMPs and DAMPs, the TLRs they activate, and their downstream signaling
      molecules have been shown to contribute to local and systemic inflammation and
      tissue damage following burn injury. Critical Issues: Whether TLR-pathway
      targeting treatments applied at different times postburn injury might improve
      scarring remains an open question. The evaluation of this question requires the
      use of appropriate preclinical and clinical burn models carried out until after
      mature scar has formed. Future Directions: After TLR-pathway-targeting treatments
      are evaluated in porcine burn wound models and their safety is demonstrated, they
      can be tested in proof-of-concept clinical burn wound models.

PMID- 29062591
TI  - Toll-Like Receptor Function in Acute Wounds.
AB  - Significance: Inflammation is an integral part of immune response and supports
      optimal wound healing in adults. Inflammatory cells such as neutrophils,
      macrophages, dendritic cells, lymphocytes, and mast cells produce important
      cytokines, chemokines, and growth factors. These immune cells interact with
      keratinocytes, fibroblasts, and endothelial cells (ECs), as well as the
      extracellular matrix within a complicated network that promotes and regulates
      wound healing. Aberrant and persistent inflammation may result in delayed wound
      healing, scar formation, or chronic wounds. Targeting the molecules involved in
      the inflammatory response may have great potential therapeutic value. Recent
      Advances and Critical Issues: Toll-like receptors (TLRs) are pattern recognition
      receptors that recognize pathogen-associated molecular patterns from microbes or
      danger-associated molecular patterns from damaged cells. The discovery of TLRs
      sheds new light on the mechanism by which the inflammatory or innate immune
      response is initiated in wound healing. Convincing evidence now shows that
      multiple types of cells, including infiltrating or resident inflammatory cells,
      keratinocytes, fibroblasts, and ECs, express specific types of TLRs. Experimental
      reduction of certain TLRs or treatment of wounds with TLR ligands has been shown
      to affect wound healing. A better understanding of the involvement of TLRs in the
      innate immune response during skin wound healing may suggest novel strategies to
      improve the quality of tissue repair. Future Directions: Despite the indisputable
      role of TLRs in regulating the immune response in acute wound healing, the
      functions of TLRs that are relevant to human wound healing and chronic wounds are
      poorly understood.

PMID- 29062592
TI  - Toll-Like Receptor-4 Signaling Drives Persistent Fibroblast Activation and
      Prevents Fibrosis Resolution in Scleroderma.
AB  - Significance: This review provides current overview of the emerging role of
      innate immunity in driving fibrosis, and preventing its resolution, in
      scleroderma (systemic sclerosis, SSc). Understanding the mechanisms of
      dysregulated innate immunity in fibrosis and SSc will provide opportunities for
      therapeutic interventions using novel agents and repurposed existing drugs.
      Recent Advances: New insights from genomic and genetic studies implicate
      components of innate immune signaling such as pattern recognition receptors
      (PRRs), downstream signaling intermediates, and endogenous inhibitors, in
      fibrosis in SSc. Recent studies distinguish innate immune signaling in tissue
      resident myofibroblasts and bone marrow-derived immune cells and define their
      roles in the development and persistence of tissue fibrosis. Critical Issues:
      Activation of toll-like receptors (TLRs) and other PRR mechanisms occurs in
      resident nonimmune cells within injured tissue microenvironments. These cells
      respond to damage-associated molecular patterns (DAMPs), such as tenascin-C that
      are recognized as danger signals, and elicit matrix production, cytokine
      secretion, and myofibroblast transformation and survival. When these responses
      persist due to constitutive TLR activation or impaired termination by endogenous
      inhibitors, they interfere with fibrosis resolution. The genetic basis and
      molecular mechanisms of these phenomena in the context of fibrosis are under
      current investigation. Future Directions: Precise delineation of the pathogenic
      DAMPs, their interaction with TLRs and other PRRs, the downstream signaling
      pathways and transcriptional events, and the fibroblast-specific regulation and
      function of endogenous inhibitors of innate immunity, will form the foundation
      for innovative targeted therapies to block fibrosis by reestablishing balanced
      innate immune signaling in fibroblasts.

PMID- 29062593
TI  - Clinical Criteria Versus a Possible Research Case Definition in Chronic Fatigue
      Syndrome/Myalgic Encephalomyelitis.
AB  - BACKGROUND: The Institute of Medicine (IOM) recently developed clinical criteria
      for what had been known as chronic fatigue syndrome (CFS). Given the broad nature
      of the clinical IOM criteria, there is a need for a research definition that
      would select a more homogenous and impaired group of patients than the IOM
      clinical criteria. At the present time, it is unclear what will serve as the
      research definition. PURPOSE: The current study focused on a research definition
      which selected homebound individuals who met the four IOM criteria, excluding
      medical and psychiatric co-morbidities. METHODS: Our research criteria were
      compared to those participants meeting the IOM criteria. Those not meeting either
      of these criteria sets were placed in a separate group defined by 6 or more
      months of fatigue. Data analyzed were from the DePaul Symptom Questionnaire and
      the SF-36. Due to unequal sample sizes and variances, Welch's F tests and Games
      Howell post hoc tests were conducted. RESULTS: Using a large database of over
      1,000 patients from several countries, we found that those meeting a more
      restrictive research definition were even more impaired and more symptomatic than
      those meeting criteria for the other two groups. CONCLUSION: Deciding on a
      particular research case definition would allow researchers to select more
      comparable patient samples across settings, and this would represent one of the
      most significant methodologic advances for this field of study.

PMID- 29062595
TI  - Phenomenology and Social Agent Representation in Psychosis: A Welcome
      Integration.

PMID- 29062594
TI  - New Drugs and New Posterior Delivery Methods in CME.
AB  - PURPOSE: To discuss the characteristics, indications and adverse events (AEs) of
      sustained-release corticosteroid devices for the treatment of cystoid macular
      edema (CME). RECENT FINDINGS: Ozurdex(r) is approved for the treatment of
      diabetic macular edema (DME), retinal vein occlusion related-CME and
      noninfectious posterior uveitis (NIPU). It releases dexamethasone over a maximum
      period of 6 months making repeated intravitreal injections necessary for
      recurrent CME. Iluvien(r) releases fluocinolone for up to 36 months and is
      effective for the treatment of chronic DME. Retisert(r) (Bausch & Lomb,
      Rochester, NY) also releases fluocinolone, and is approved for chronic NIPU. Both
      Iluvien(r) and Retisert(r) are non-biodegradable devices and are highly
      associated with cataract and glaucoma. SUMMARY: Long-acting intraocular
      corticosteroid formulations offer a more predictable drug-release profile and
      reduced dosing frequency in comparison to conventional formulations of the same
      compounds but the risk-benefit ratio must be taken into consideration previous to
      the implantation of those devices.

PMID- 29062596
TI  - Exploring the psychological health of emergency dispatch centre operatives: a
      systematic review and narrative synthesis.
AB  - BACKGROUND: The study objective was to investigate and synthesize available
      evidence relating to the psychological health of Emergency Dispatch Centre (EDC)
      operatives, and to identify key stressors experienced by EDC operatives. METHODS:
      Eight electronic databases (Embase, PubMed, Medline, CINAHL, PsycInfo,
      PsycArticles, The Psychology and Behavioural Sciences Collection, and Google
      Scholar) were searched. All study designs were included, and no date limits were
      set. Studies were included if they were published in English, and explored the
      psychological health of any EDC operatives, across fire, police, and emergency
      medical services. Studies were excluded if they related solely to other emergency
      workers, such as police officers or paramedics. Methodological quality of
      included studies was assessed using checklists adapted from the Critical
      Appraisal Skills Programme. A narrative synthesis was conducted, using thematic
      analysis. RESULTS: A total of 16 articles were included in the review. Two
      overarching themes were identified during the narrative synthesis:
      'Organisational and Operational Factors' and 'Interactions with Others'.
      Stressors identified included being exposed to traumatic calls, lacking control
      over high workload, and working in under-resourced and pressured environments.
      Lack of support from management and providing an emotionally demanding service
      were additional sources of stress. Peer support and social support from friends
      and family were helpful in managing work-related stress. DISCUSSION: EDC
      operatives experience stress as a result of their work, which appears to be
      related to negative psychological health outcomes. Future research should explore
      the long-term effects of this stress, and the potential for workplace
      interventions to alleviate the negative impacts on psychological health. PROSPERO
      REGISTRATION NUMBER: CRD42014010806.

PMID- 29062597
TI  - Ongoing removals of invasive lionfish in Honduras and their effect on native
      Caribbean prey fishes.
AB  - The invasion of Indo-Pacific lionfish is one of the most pressing concerns in the
      context of coral reef conservation throughout the Caribbean. Invasive lionfish
      threaten Caribbean fish communities by feeding on a wide range of native prey
      species, some of which have high ecological and economic value. In Roatan
      (Honduras) a local non-governmental organisation (i.e. Roatan Marine Park) trains
      residents and tourists in the use of spears to remove invasive lionfish. Here, we
      assess the effectiveness of local removal efforts in reducing lionfish
      populations. We ask whether reefs subject to relatively frequent removals support
      more diverse and abundant native fish assemblages compared to sites were no
      removals take place. Lionfish biomass, as well as density and diversity of native
      prey species were quantified on reefs subject to regular and no removal efforts.
      Reefs subject to regular lionfish removals (two to three removals month-1) with a
      mean catch per unit effort of 2.76 +/- 1.72 lionfish fisher-1 h-1 had 95% lower
      lionfish biomass compared to non-removal sites. Sites subject to lionfish
      removals supported 30% higher densities of native prey-sized fishes compared to
      sites subject to no removal efforts. We found no evidence that species richness
      and diversity of native fish communities differ between removal and non-removal
      sites. We conclude that opportunistic voluntary removals are an effective
      management intervention to reduce lionfish populations locally and might
      alleviate negative impacts of lionfish predation. We recommend that local
      management and the diving industry cooperate to cost-effectively extend the
      spatial scale at which removal regimes are currently sustained.

PMID- 29062598
TI  - How to normalize metatranscriptomic count data for differential expression
      analysis.
AB  - BACKGROUND: Differential expression analysis on the basis of RNA-Seq count data
      has become a standard tool in transcriptomics. Several studies have shown that
      prior normalization of the data is crucial for a reliable detection of
      transcriptional differences. Until now it has not been clear whether and how the
      transcriptomic approach can be used for differential expression analysis in
      metatranscriptomics. METHODS: We propose a model for differential expression in
      metatranscriptomics that explicitly accounts for variations in the taxonomic
      composition of transcripts across different samples. As a main consequence the
      correct normalization of metatranscriptomic count data under this model requires
      the taxonomic separation of the data into organism-specific bins. Then the taxon
      specific scaling of organism profiles yields a valid normalization and allows us
      to recombine the scaled profiles into a metatranscriptomic count matrix. This
      matrix can then be analyzed with statistical tools for transcriptomic count data.
      For taxon-specific scaling and recombination of scaled counts we provide a simple
      R script. RESULTS: When applying transcriptomic tools for differential expression
      analysis directly to metatranscriptomic data with an organism-independent
      (global) scaling of counts the resulting differences may be difficult to
      interpret. The differences may correspond to changing functional profiles of the
      contributing organisms but may also result from a variation of taxonomic
      abundances. Taxon-specific scaling eliminates this variation and therefore the
      resulting differences actually reflect a different behavior of organisms under
      changing conditions. In simulation studies we show that the divergence between
      results from global and taxon-specific scaling can be drastic. In particular, the
      variation of organism abundances can imply a considerable increase of significant
      differences with global scaling. Also, on real metatranscriptomic data, the
      predictions from taxon-specific and global scaling can differ widely. Our studies
      indicate that in real data applications performed with global scaling it might be
      impossible to distinguish between differential expression in terms of
      transcriptomic changes and differential composition in terms of changing
      taxonomic proportions. CONCLUSIONS: As in transcriptomics, a proper normalization
      of count data is also essential for differential expression analysis in
      metatranscriptomics. Our model implies a taxon-specific scaling of counts for
      normalization of the data. The application of taxon-specific scaling consequently
      removes taxonomic composition variations from functional profiles and therefore
      provides a clear interpretation of the observed functional differences.

PMID- 29062599
TI  - Investigating the level of agreement of two positioning protocols when using dual
      energy X-ray absorptiometry in the assessment of body composition.
AB  - BACKGROUND: Dual energy X-ray absorptiometry (DXA) is a commonly used instrument
      for analysing segmental body composition (BC). The information from the scan
      guides the clinician in the treatment of conditions such as obesity and can be
      used to monitor recovery of lean mass following injury. Two commonly used DXA
      positioning protocols have been identified-the Nana positioning protocol and the
      National Health and Nutrition Examination Survey (NHANES). Both protocols have
      been shown to be reliable. However, only one study has assessed the level of
      agreement between the protocols and ascertained the participants' preference of
      protocol based upon comfort. Given the paucity of research in the field and the
      growing use of DXA in both healthy and pathological populations further research
      determining the most appropriate positioning protocol is warranted. Therefore,
      the aims of this study were to assess the level of agreement between results from
      the NHANES protocol and Nana protocol, and the participants' preference of
      protocol based on comfort. METHODS: Thirty healthy participants (15 males, 15
      females, aged 23-59 years) volunteered to participate in this study. These
      participants underwent two whole body DXA scans in a single morning (Nana
      positioning protocol and NHANES positioning protocol), in a randomised order.
      Each participant attended for scanning wearing minimal clothing and having fasted
      overnight, refrained from exercise in the past 24 h and voided their bladders.
      Level of agreement, comparing NAHNES to Nana protocol was assessed using an intra
      class correlation coefficient (ICC), concordance correlation coefficient (CCC)
      and percentage change in mean. Limit of agreement comparing the two protocols
      were assessed using plots, mean difference and confidence limits. Participants
      were asked to indicate the protocol they found most comfortable. RESULTS: When
      assessing level of agreement between protocols both the ICC and CCC scores were
      very high and ranged from 0.987 to 0.997 for whole body composition, indicating
      excellent agreement between the Nana and NHANES protocols. Regional analysis
      (arms, legs, trunk) ICC scores, ranged between 0.966 and 0.996, CCC ranged
      between 0.964 and 0.997, change in mean percentage ranged between -0.58% and
      0.37% which indicated a very high level of agreement. Limit of agreement analysis
      using mean difference ranged between -0.223 and 0.686 kg and 95% CL produced
      results ranging between -1.262 kg and 1.630 kg. The majority (80%) of
      participants found the NHANES positioning protocol more comfortable. DISCUSSION:
      This study reveals a strong level of agreement as illustrated by high ICC's and
      CCC's between the positioning protocols, however systematic bias within limit of
      agreement plot and a large difference in 95% confidence limits indicates that the
      protocols should not be interchanged when assessing an individual. The NHANES
      protocol affords greater participant comfort.

PMID- 29062600
TI  - L1 and L2 reading skills in Dutch adolescents with a familial risk of dyslexia.
AB  - BACKGROUND: The present study investigated differences in reading and spelling
      outcomes in Dutch and English as a second language (ESL) in adolescents with a
      high familial risk of dyslexia, of whom some have developed dyslexia (HRDys)
      while others have not (HRnonDys), in comparison to a low familial risk control
      group without dyslexia (LRnonDys). This allowed us to investigate the persistence
      of dyslexia in the first language (L1) and the effect of dyslexia on the second
      language (L2), which has, in this case, a lower orthographic transparency.
      Furthermore, the inclusion of the HRnonDys group allowed us to investigate the
      continuity of the familial risk of dyslexia, as previous studies observed that
      the HRnonDys group often scores in between the HRDys and LRnonDys group, and
      whether these readers without reading deficits in Dutch, have more reading
      difficulties in ESL. METHODS: The data of three groups of adolescents were
      analyzed; 27 LRnonDys, 25 HRdys 25 HRnonDys. The mean age was 14;1 years; months,
      and 37 were male. All were native speakers of Dutch, attended regular secondary
      education (grade 7-10), and were non-native speakers of English. Using MANOVA the
      groups were compared on Dutch and English word reading fluency (WRF), spelling
      and vocabulary, Dutch pseudoword and loanword reading fluency, phonological
      awareness (PA), rapid automatized naming (RAN), and verbal short term and working
      memory. A repeated measures ANOVA was used to compare English and Dutch WRF,
      spelling and vocabulary directly within the three groups. RESULTS: The analyses
      revealed that the HRDys group had a deficit in both reading and spelling in Dutch
      and ESL. They also performed poorer than the LRnonDys group on all other
      measures. Effect sizes were especially large for pseudoword reading and the
      reaction times during the PA task. The HRnonDys group scored generally poorer
      than the LRnonDys group but this difference was only significant for Dutch
      pseudoword reading, PA reaction times and verbal short term memory. In general
      the HRDys and HRnonDys group scored similar in Dutch and English, except for
      English WRF where the HRDys group scored slightly better than expected based on
      their Dutch WRF. DISCUSSION: There was a high persistence of dyslexia.
      Adolescents with dyslexia had large impairments in reading and spelling, and
      reading related measures, both in Dutch and ESL. Despite high inter-individual
      differences, an overall three-step pattern was observed. Adolescents in the
      HRnonDys group scored in between the HRDys and LRnonDys group, supporting the
      polygenetic origin of dyslexia and the continuity of the familial risk of
      dyslexia. The lower orthographic transparency did not have a negative effect on
      L2 reading, spelling and vocabulary, both in the HRnonDys and HRDys group. The
      latter group performed slightly better than expected in L2, which may be a result
      of the massive exposure to English and high motivation to use English by
      adolescents.

PMID- 29062601
TI  - Effects of GnRHa treatment during vitellogenesis on the reproductive physiology
      of thermally challenged female Atlantic salmon (Salmo salar).
AB  - Tasmanian Atlantic salmon (S. salar) broodstock can experience temperatures above
      20  degrees C, which impairs reproductive development and inhibits ovulation. The
      present study investigated the prolonged use of gonadotropin releasing hormone
      analogue (GnRHa) during vitellogenesis as a means of maintaining endocrine
      function and promoting egg quality at elevated temperature in maiden and repeat
      spawning S. salar. GnRHa-treatment during vitellogenesis did not compensate for
      the negative effects of thermal challenge on the timing of ovulation, egg size,
      egg fertility or embryo survival in any fish maintained at 22  degrees C relative
      to 14  degrees C. The lack of effectiveness was reflected by the endocrine data,
      as plasma follicle stimulating hormone and luteinising hormone levels were not
      different between treated and untreated groups at 22  degrees C. Furthermore,
      plasma testosterone and E2 levels were unchanged in GnRHa-treated fish at 22 
      degrees C, and plasma levels were generally lower in both groups maintained at 22
      degrees C relative to 14  degrees C. Transcription of vitellogenin, and zona
      pellucida B and C was not enhanced in GnRHa-treated fish relative to untreated
      fish at 22  degrees C, presumably due to observed suppression of plasma E2. These
      results indicate that thermal impairment of reproduction is likely to occur on
      multiple levels, and is difficult to overcome via hormonal manipulation.

PMID- 29062602
TI  - Range expansion of a fouling species indirectly impacts local species
      interactions.
AB  - We investigated how recent changes in the distribution and abundance of a fouling
      organism affected the strength of interactions between a commercially important
      foundation species and a common predator. Increases in the abundance of boring
      sponges that bioerode the calcified shells of oysters and other shelled organisms
      have been attributed to increased salinization of estuarine ecosystems. We tested
      the hypothesis that fouling by boring sponges will change the interaction
      strength between oysters and a common predator (stone crabs). We generated five
      oyster density treatments crossed with two sponge treatments (sponge and no
      sponge). We contrasted the interaction strength between stone crabs and fouled
      and non-fouled oysters by comparing the parameters of fitted functional response
      curves based on Rogers random predation model. We found that fouled oysters
      suffered higher predation from stone crabs, and that the increased predation risk
      stemmed from a reduction in the handling time needed to consume the fouled
      oysters. These findings highlight the importance of understanding the effects of
      abiotic changes on both the composition of ecological communities, and on the
      strengths of direct and indirect interactions among species. Global climate
      change is altering local ecosystems in complex ways, and the success of
      restoration, management, and mitigation strategies for important species requires
      a better appreciation for how these effects cascade through ecosystems.

PMID- 29062604
TI  - Bacterial and fungal communities respond differently to varying tillage depth in
      agricultural soils.
AB  - In arable cropping systems, reduced or conservation tillage practices are linked
      with improved soil quality, C retention and higher microbial biomass, but most
      long-term studies rarely focus on depths greater than 15 cm nor allow comparison
      of microbial community responses to agricultural practices. We investigated
      microbial community structure in a long-term field trial (12-years, Lincoln, New
      Zealand) established in a silt-loam soil over four depth ranges down to 30 cm.
      Our objectives were to investigate the degree of homogenisation of soil
      biological and chemical properties with depth, and to determine the main drivers
      of microbial community response to tillage. We hypothesised that soil
      microbiological responses would depend on tillage depth, observed by a
      homogenisation of microbial community composition within the tilled zone. Tillage
      treatments were mouldboard plough and disc harrow, impacting soil to ~20 and ~10
      cm depth, respectively. These treatments were compared to a no-tillage treatment
      and two control treatments, both permanent pasture and permanent fallow.
      Bacterial and fungal communities collected from the site were not impacted by the
      spatial location of sampling across the study area but were affected by
      physicochemical changes associated with tillage induced soil homogenisation and
      plant presence. Tillage treatment effects on both species richness and
      composition were more evident for bacterial communities than fungal communities,
      and were greater at depths <15 cm. Homogenisation of soil and changing land
      management appears to redistribute both microbiota and nutrients deeper in the
      soil profile while consequences for soil biogeochemical functioning remain poorly
      understood.

PMID- 29062603
TI  - Decreased quality of life and treatment satisfaction in patients with latent
      autoimmune diabetes of the adult.
AB  - OBJECTIVES: Our main aim was to assess the quality of life (QoL) and treatment
      satisfaction (TS) of subjects with LADA (latent autoimmune diabetes of the adult)
      and compare these measures with those of patients with other diabetes types,
      i.e., type 1 (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: This was a
      cross-sectional study with a total of 48 patients with LADA, 297 patients with
      T2DM and 124 with T1DM. The Audit of Diabetes-Dependent Quality of Life (ADDQoL
      19) questionnaire and the Diabetes Treatment Satisfaction Questionnaire (DTSQ)
      were administered. Relevant clinical variables were also assessed. The data
      analysis included comparisons between groups and multivariate linear models.
      RESULTS: The LADA patients presented lower diabetes-specific QoL (p = 0.045) and
      average weighted impact scores (p = 0.007) than the T2DM patients. The subgroup
      of LADA patients with diabetic retinopathy (DR) who were treated with insulin had
      a lower ADDQoL average weighted impact score than the other diabetic groups.
      Although the overall measure of TS was not different between the LADA and T2DM (p
      = 0.389) and T1DM (p = 0.091) groups, the patients with LADA showed a poorer
      hyperglycemic frequency perception than the T2DM patients (p < 0.001) and an
      improved frequency of hypoglycemic perception compared with the T1DM patients (p
      = 0.021). CONCLUSIONS: The current findings suggest a poorer quality of life,
      especially in terms of DR and insulin treatment, among patients with LADA
      compared with those with T1DM and T2DM. Hyperglycemia frequency perception was
      also poorer in the LADA patients than in the T1DM and T2DM patients. Further
      research with prospective studies and a large number of patients is necessary.

PMID- 29062605
TI  - Influence of current climate, historical climate stability and topography on
      species richness and endemism in Mesoamerican geophyte plants.
AB  - BACKGROUND: A number of biotic and abiotic factors have been proposed as drivers
      of geographic variation in species richness. As biotic elements, inter-specific
      interactions are the most widely recognized. Among abiotic factors, in particular
      for plants, climate and topographic variables as well as their historical
      variation have been correlated with species richness and endemism. In this study,
      we determine the extent to which the species richness and endemism of monocot
      geophyte species in Mesoamerica is predicted by current climate, historical
      climate stability and topography. METHODS: Using approximately 2,650 occurrence
      points representing 507 geophyte taxa, species richness (SR) and weighted
      endemism (WE) were estimated at a geographic scale using grids of 0.5 * 0.5
      decimal degrees resolution using Mexico as the geographic extent. SR and WE were
      also estimated using species distributions inferred from ecological niche
      modeling for species with at least five spatially unique occurrence points.
      Current climate, current to Last Glacial Maximum temperature, precipitation
      stability and topographic features were used as predictor variables on multiple
      spatial regression analyses (i.e., spatial autoregressive models, SAR) using the
      estimates of SR and WE as response variables. The standardized coefficients of
      the predictor variables that were significant in the regression models were
      utilized to understand the observed patterns of species richness and endemism.
      RESULTS: Our estimates of SR and WE based on direct occurrence data and
      distribution modeling generally yielded similar results, though estimates based
      on ecological niche modeling indicated broader distribution areas for SR and WE
      than when species richness was directly estimated using georeferenced
      coordinates. The SR and WE of monocot geophytes were highest along the Trans
      Mexican Volcanic Belt, in both cases with higher levels in the central area of
      this mountain chain. Richness and endemism were also elevated in the southern
      regions of the Sierra Madre Oriental and Occidental mountain ranges, and in the
      Tehuacan Valley. Some areas of the Sierra Madre del Sur and Sierra Madre Oriental
      had high levels of WE, though they are not the areas with the highest SR. The
      spatial regressions suggest that SR is mostly influenced by current climate,
      whereas endemism is mainly affected by topography and precipitation stability.
      CONCLUSIONS: Both methods (direct occurrence data and ecological niche modeling)
      used to estimate SR and WE in this study yielded similar results and detected a
      key area that should be considered in plant conservation strategies: the central
      region of the Trans-Mexican Volcanic Belt. Our results also corroborated that
      species richness is more closely correlated with current climate factors while
      endemism is related to differences in topography and to changes in precipitation
      levels compared to the LGM climatic conditions.

PMID- 29062607
TI  - Tolerance: the forgotten child of plant resistance.
AB  - Plant resistance against insect herbivory has greatly focused on antibiosis,
      whereby the plant has a deleterious effect on the herbivore, and antixenosis,
      whereby the plant is able to direct the herbivore away from it. Although these
      two types of resistance may reduce injury and yield loss, they can produce
      selection pressures on insect herbivores that lead to pest resistance. Tolerance,
      on the other hand, is a more sustainable pest management strategy because it
      involves only a plant response and therefore does not cause evolution of
      resistance in target pest populations. Despite its attractive attributes,
      tolerance has been poorly studied and understood. In this critical, interpretive
      review, we discuss tolerance to insect herbivory and the biological and
      socioeconomic factors that have limited its use in plant resistance and
      integrated pest management. First, tolerance is difficult to identify, and the
      mechanisms conferring it are poorly understood. Second, the genetics of tolerance
      are mostly unknown. Third, several obstacles hinder the establishment of high
      throughput phenotyping methods for large-scale screening of tolerance. Fourth,
      tolerance has received little attention from entomologists because, for most,
      their primary interest, research training, and funding opportunities are in
      mechanisms which affect pest biology, not plant biology. Fifth, the efforts of
      plant resistance are directed at controlling pest populations rather than
      managing plant stress. We conclude this paper by discussing future research and
      development activities.

PMID- 29062606
TI  - The neuroprotective effect of nicotine in Parkinson's disease models is
      associated with inhibiting PARP-1 and caspase-3 cleavage.
AB  - Clinical evidence points to neuroprotective effects of smoking in Parkinson's
      disease (PD), but the molecular mechanisms remain unclear. We investigated the
      pharmacological pathways involved in these neuroprotective effects, which could
      provide novel ideas for developing targeted neuroprotective treatments for PD. We
      used the ETC complex I inhibitor methylpyridinium ion (MPP+) to induce cell death
      in SH-SY5Y cells as a cellular model for PD and found that nicotine inhibits cell
      death. Using choline as a nicotinic acetylcholine receptor (nAChR) agonist, we
      found that nAChR stimulation was sufficient to protect SH-SY5Y cells against cell
      death from MPP+. Blocking alpha7 nAChR with methyllycaconitine (MLA) prevented
      the protective effects of nicotine, demonstrating that these receptors are
      necessary for the neuroprotective effects of nicotine. The neuroprotective effect
      of nicotine involves other pathways relevant to PD. Cleaved Poly (ADP-ribose)
      polymerase-1 (PARP-1) and cleaved caspase-3 were decreased by nicotine in 6
      hydroxydopamine (6-OHDA) lesioned mice and in MPP+-treated SH-SY5Y cells. In
      conclusion, our data indicate that nicotine likely exerts neuroprotective effects
      in PD through the alpha7 nAChR and downstream pathways including PARP-1 and
      caspase-3. This knowledge could be pursued in future research to develop
      neuroprotective treatments for PD.

PMID- 29062608
TI  - MGST2 and WNT2 are candidate genes for comitant strabismus susceptibility in
      Japanese patients.
AB  - BACKGROUND/AIM: Strabismus is a common condition with misalignment between two
      eyes that may lead to decrease of visual acuity, lack of binocularity, and
      diplopia. It is caused by heterogeneous environmental and genetic risk factors.
      Our previous research has identified new chromosomal susceptibility loci in
      4q28.3 and 7q31.2 regions for comitant strabismus in Japanese families. We
      conducted a verification study by linkage analysis to narrow the chromosomal loci
      down to a single gene. METHODS: From Japanese and U.S. databases, 24 rsSNPs and
      233 rsSNPs were chosen from the 4q28.3 and 7q31.2 region, respectively, and were
      typed in 108 affected subjects and 96 unaffected subjects of 58 families with
      primary and non-syndromic comitant strabismus. Three major analytical methods
      were used: transmission disequilibrium test (TDT), TDT allowing for errors
      (TDTae), and linkage analysis under dominant and recessive inheritance. RESULTS:
      The SNPs with significant P values in TDT and TDTae were located solely at the
      gene, microsomal glutathione S-transferase 2 (MGST2), on chromosome 4q28.3 locus.
      In contrast, significant SNPs were dispersed in a few genes, containing wingless
      type MMTV integration site family member 2 (WNT2), on chromosome 7q31.2 locus.
      The distribution of significant SNPs on the 7q31.2 locus showed that only the ST7
      to WNT2 region in the same big haplotype block contained significant SNPs for all
      three methods of linkage analysis. CONCLUSIONS: This study suggests that MGST2
      and WNT2 are potential candidates for comitant strabismus in Japanese population.

PMID- 29062609
TI  - Microbial community diversity patterns are related to physical and chemical
      differences among temperate lakes near Beaver Island, MI.
AB  - Lakes are dynamic and complex ecosystems that can be influenced by physical,
      chemical, and biological processes. Additionally, individual lakes are often
      chemically and physically distinct, even within the same geographic region. Here
      we show that differences in physicochemical conditions among freshwater lakes
      located on (and around) the same island, as well as within the water column of
      each lake, are significantly related to aquatic microbial community diversity.
      Water samples were collected over time from the surface and bottom-water within
      four freshwater lakes located around Beaver Island, MI within the Laurentian
      Great Lakes region. Three of the sampled lakes experienced seasonal lake mixing
      events, impacting either O2, pH, temperature, or a combination of the three.
      Microbial community alpha and beta diversity were assessed and individual
      microbial taxa were identified via high-throughput sequencing of the 16S rRNA
      gene. Results demonstrated that physical and chemical variability (temperature,
      dissolved oxygen, and pH) were significantly related to divergence in the beta
      diversity of surface and bottom-water microbial communities. Despite its
      correlation to microbial community structure in unconstrained analyses,
      constrained analyses demonstrated that dissolved organic carbon (DOC)
      concentration was not strongly related to microbial community structure among or
      within lakes. Additionally, several taxa were correlated (either positively or
      negatively) to environmental variables, which could be related to aerobic and
      anaerobic metabolisms. This study highlights the measurable relationships between
      environmental conditions and microbial communities within freshwater temperate
      lakes around the same island.

PMID- 29062610
TI  - The benefits of Tai Chi and brisk walking for cognitive function and fitness in
      older adults.
AB  - The purpose of this study was to investigate the benefits of exercises with
      different cognitive demands for cognitive functions (Executive and non-Executive)
      in healthy older adults. A cross-sectional design was adopted. In total, 84
      healthy older adults were enrolled in the study. They were categorized into the
      Tai Chi group (TG), the brisk walking group (BG) or the control group (CG). Each
      participant performed the Stroop task and a digit comparison task. The Stroop
      task included the following three conditions: a naming condition, an inhibition
      condition and an executive condition. There were two experimental conditions in
      the digit comparison task: the non-delay condition and the delay condition. The
      results indicated that participants of the TG and BG revealed significant better
      performance than the CG in the executive condition of cognitive tasks and
      fitness. There was no significant difference of reaction time (RT) and accuracy
      rate in the inhibition and delay conditions of cognitive tasks and fitness
      between the TG and BG. The TG showed shorter reaction time in the naming and the
      executive conditions, and more accurate in the inhibition conditions than the BG.
      These findings demonstrated that regular participation in brisk walking and Tai
      Chi have significant beneficial effects on executive function and fitness.
      However, due to the high cognitive demands of the exercise, Tai Chi benefit
      cognitive functions (Executive and non-Executive) in older adults more than brisk
      walking does. Further studies should research the underlying mechanisms at the
      behavioural and neuroelectric levels, providing more evidence to explain the
      effect of high-cognitive demands exercise on different processing levels of
      cognition.

PMID- 29062611
TI  - Oxygen-limited metabolism in the methanotroph Methylomicrobium buryatense 5GB1C.
AB  - The bacteria that grow on methane aerobically (methanotrophs) support populations
      of non-methanotrophs in the natural environment by excreting methane-derived
      carbon. One group of excreted compounds are short-chain organic acids, generated
      in highest abundance when cultures are grown under O2-starvation. We examined
      this O2-starvation condition in the methanotroph Methylomicrobium buryatense
      5GB1. The M. buryatense 5GB1 genome contains homologs for all enzymes necessary
      for a fermentative metabolism, and we hypothesize that a metabolic switch to
      fermentation can be induced by low-O2 conditions. Under prolonged O2-starvation
      in a closed vial, this methanotroph increases the amount of acetate excreted
      about 10-fold, but the formate, lactate, and succinate excreted do not respond to
      this culture condition. In bioreactor cultures, the amount of each excreted
      product is similar across a range of growth rates and limiting substrates,
      including O2-limitation. A set of mutants were generated in genes predicted to be
      involved in generating or regulating excretion of these compounds and tested for
      growth defects, and changes in excretion products. The phenotypes and associated
      metabolic flux modeling suggested that in M. buryatense 5GB1, formate and acetate
      are excreted in response to redox imbalance. Our results indicate that even under
      O2-starvation conditions, M. buryatense 5GB1 maintains a metabolic state
      representing a combination of fermentation and respiration metabolism.

PMID- 29062612
TI  - lncRNA H19 is involved in TGF-beta1-induced epithelial to mesenchymal transition
      in bovine epithelial cells through PI3K/AKT Signaling Pathway.
AB  - Increased levels of long noncoding RNA H19 (H19) have been observed in many
      inflammatory and organ fibrosis diseases including ulcerative colitis,
      osteoarthritis, liver fibrosis, renal fibrosis and pulmonary fibrosis. However,
      the role of H19 in bovine mastitis and mastitis-caused fibrosis is still unclear.
      In our study, H19 was characterized as a novel regulator of EMT induced by
      transforming growth factor-beta1 (TGF-beta1) in bovine mammary alveolar cell-T
      (MAC-T) cell line. We found that H19 was highly expressed in bovine mastitis
      tissues and inflammatory MAC-T cells induced by virulence factors of pathogens.
      TGF-beta1 was also highly expressed in inflammatory MAC-T cells, and exogenous
      TGF-beta1 could induce EMT, enhance extracellular matrix protein expression, and
      upregulate H19 expression in epithelial cells. Stable expression of H19
      significantly promotes EMT progression and expression of ECM protein induced by
      TGF-beta1 in MAC-T cells. Furthermore, by using a specific inhibitor of the
      PI3K/AKT pathway, we demonstrated that TGF-beta1 upregulated H19 expression
      through PI3K/AKT pathway. All these observations imply that the lncRNA H19
      modulated TGF-beta1-induced epithelial to mesenchymal transition in bovine
      epithelial cells through PI3K/AKT signaling pathway, which suggests that mammary
      epithelial cells might be one source for myofibroblasts in vivo in the mammary
      glands under an inflammatory condition, thereby contributing to mammary gland
      fibrosis.

PMID- 29062614
TI  - Simultaneous Anterior Glenohumeral Dislocation and Ipsilateral Acromioclavicular
      Separation: A Dual Injury of the Shoulder.
AB  - Isolated acromioclavicular separations or shoulder dislocations are common
      injuries. However, a combination of complete acromioclavicular separation and
      anterior shoulder dislocation is extremely rare. Herein we present a combination
      of anterior shoulder dislocation and type III acromioclavicular separation that
      was succesfully treated conservatively. Orthopaedic surgeons should have a high
      clinical suspicion in daily practice. We believe that both pathologies can be
      treated conservatively.

PMID- 29062615
TI  - Venous Stent Migration into Right Ventricle.
AB  - Venous stents (VS) are used to treat central and peripheral stenoses. Stent
      embolization into a cardiac chamber is a rare, yet serious complication. We
      present a case of a 61-year-old man with a recently stented arteriovenous graft
      venous stenosis who developed VS migration into the right ventricle, associated
      with S. aureus bacteremia.

PMID- 29062616
TI  - Association of Internal Mammary Artery Flow with Different Comorbidities and Post
      Coronary Artery Bypass Graft Complications.
AB  - Objective The internal mammary artery (IMA) is commonly used arterial graft for
      coronary artery bypass surgery (CABG). The IMA has a better patency and survival.
      This study considers different comorbidities and conditions where IMA flow may be
      low. Therefore, the main objective is to determine the flow of IMA in different
      diseases, its relation to gender, age, and in different blood groups in order to
      prevent possible complications. Methods A prospective study was conducted at the
      Cardiac Surgery Unit, Civil Hospital Karachi from January 2013 to December 2015.
      The data of 158 patients who underwent primary, isolated, and CABG surgery was
      collected. Free flow of IMA was measured immediately after harvesting for 30
      seconds within a syringe, and its relationship with different diseases and
      conditions was examined. Data was collected using a structured questionnaire from
      the patients' medical record files and it was later analyzed and entered into the
      Statistical Package for Social Sciences (SPSS) software, V17 (IBM SPSS
      Statistics, Armonk, NY). Results The mean flow was 11.6 +/- 9.6 ml. There was no
      difference in flow related to gender, diabetes, smoking, renal disease, and
      chronic obstructive pulmonary disease (COPD). There was significantly higher flow
      in the age group of 50 to 60 years (p = 0.002), hypertensive patients (p =
      0.016), patients with liver disease (p = 0.001), BMI > 30 (p = 0.041), and the
      blood group AB+ (p = 0.02). The atrial fibrillation and readmissions were higher
      in patients who had low flow. Low flow IMA, which was used on left anterior
      descending (LAD) artery stenosis patients, showed a significantly higher need of
      pharmacological and mechanical support. Conclusion IMA should be used carefully
      in patients where its flow is low; conditions must be analyzed where flow may be
      low to avoid complications. Further studies are warranted.

PMID- 29062613
TI  - Emerging and investigational therapies for neuroblastoma.
AB  - INTRODUCTION: Treatment for children with clinically aggressive, high-risk
      neuroblastoma remains challenging. Less than 50% of patients with high-risk
      neuroblastoma will survive long-term with current therapies, and survivors are at
      risk for serious treatment-related late toxicities. Here, we review new and
      evolving treatments that may ultimately improve outcome for children with high
      risk neuroblastoma with decreased potential for late adverse events. AREAS
      COVERED: New strategies for treating high-risk neuroblastoma are reviewed
      including: radiotherapy, targeted cytotoxics, biologics, immunotherapy, and
      molecularly targeted agents. Recently completed and ongoing neuroblastoma
      clinical trials testing these novel treatments are highlighted. In addition, we
      discuss ongoing clinical trials designed to evaluate precision medicine
      approaches that target actionable somatic mutations and oncogenic cellular
      pathways. EXPERT OPINION: Advances in genomic medicine and molecular biology have
      led to the development of early phase studies testing biologically rational
      therapies targeting aberrantly activated cellular pathways. Because many of these
      drugs have a wider therapeutic index than standard chemotherapeutic agents, these
      treatments may be more effective and less toxic than current strategies. However,
      to effectively integrate these targeted strategies, robust predictive biomarkers
      must be developed that will identify patients who will benefit from these
      approaches and rapidly match treatments to patients at diagnosis.

PMID- 29062617
TI  - Marked Atrophic Changes of the Brain in a Patient with Subacute Sclerosing
      Panencephalitis.
AB  - Subacute Sclerosing Panencephalitis (SSPE) is a debilitating disorder associated
      with the measles infection in childhood. It is a very rare manifestation in
      children. It usually presents with measles before the age of two. We report a
      similar case of SSPE in a 14-year-old girl who developed this life-threatening
      condition in spite of receiving the measles vaccination. Despite the vaccination,
      the patient had suffered from measles before the age of two. This highlights the
      dilemma of ineffective vaccinations in developing countries. We also describe the
      radiologic features of SSPE in this patient, with marked atrophy seen in the
      occipital region following hyperintensities noticed at a relatively earlier
      stage.

PMID- 29062618
TI  - Health Care in Gulf Cooperation Council Countries: A Review of Challenges and
      Opportunities.
AB  - This study was undertaken to review the health care status in the Gulf
      Cooperation Council (GCC) member states, and explore current challenges and
      future opportunities. Available data was acquired using databases including
      PubMed, Embase, and Cochrane Library. The data gathered was then combined and the
      expert authors in the field discussed and propose strategies to overcome the
      challenges. There is an increase in both population and health care needs of GCC
      States citizens and migrant workers. The huge emigrant population challenges the
      capability of the already limited available health care resources. The region is
      faced with a quadruple disease burden that includes communicable and non
      communicable diseases, mental health issues and accidental injuries. Recent
      advances in technology have made breakthroughs in diagnosis and treatment
      modalities but with an increase in overall health care cost. Innovative and cost
      effective strategies are required to cater the health care needs of people living
      in the GCC states. Policy makers should emphasize the need to prioritize and
      strengthen primary care as a matter of urgency.

PMID- 29062619
TI  - Choledocholithiasis: Treatment Options in a Tertiary Care Setup in Pakistan.
AB  - Introduction Among patients with cholelithiasis, choledocholithiasis may also be
      present in about 18% of cases. They can be treated through various endoscopic,
      laparoscopic, and open surgical procedures. Objective The objective of this study
      was to determine the outcome of patients with choledocholithiasis being treated
      in our setup. Methods This descriptive case series was conducted at Holy Family
      Hospital, Rawalpindi, Pakistan over two years from January 2015 to December 2016.
      All patients with choledocholithiasis admitted to Surgical Unit 1 were included
      in this study. All patients underwent elective endoscopic retrograde
      cholangiopancreatography (ERCP). In patients with successful ERCP, laparoscopic
      or open cholecystectomy was performed at a later date. In patients in whom ERCP
      failed, open surgical clearance of the common bile duct (CBD), along with
      cholecystectomy, was done. Results A total of 200 cases of choledocholithiasis
      were admitted during the study period. Most of the participants (73%) in this
      study were female. Liver function tests were found to be deranged in 88 patients
      (44%) and normal in 112 patients (56%). At presentation, 3.5% (n=7) had
      concomitant acute biliary pancreatitis and 8% (n=16) had cholangitis. Successful
      ERCP followed by cholecystectomy was performed in 88.5% of cases. On the other
      hand, 11.5% (n=23) patients had failed ERCP due to impacted stones. They
      underwent open surgical procedures, i.e. 43.48% (n=10) had choledochotomies,
      47.82% (n=11) had choledochoduodenostomies and 8.69% (n=2) had
      hepaticojejunostomies. No postoperative mortality was observed. However,
      anastomotic leaking occurred in 8.69% cases (n=2). Conclusion A two-staged
      procedure consisting of ERCP, followed by laparoscopic cholecystectomy, should be
      the first line of treatment for common bile duct (CBD) stones. In cases where
      ERCP fails, open surgical procedures still remain a relevant and a definitive
      option in resource-constrained setups.

PMID- 29062620
TI  - Ludwig's Angina.
AB  - Ludwig's angina is a diffuse cellulitis in the submandibular, sublingual, and
      submental spaces, characterized by its propensity to spread rapidly to the
      surrounding tissues. Early recognition and treatment for Ludwig's angina are of
      paramount importance due to the myriad of complications that can occur in
      association with Ludwig's angina. Known complications of Ludwig's angina include
      carotid arterial rupture or sheath abscess, thrombophlebitis of the internal
      jugular vein, mediastinitis, empyema, pericardial effusion, osteomyelitis of the
      mandible, subphrenic abscess, aspiration pneumonia, and pleural effusion. By
      reporting a case of Ludwig's angina, we hope to raise the awareness in our
      medical community for this rare clinical entity. This case describes a 54-year
      old woman with Ludwig's angina that evolved from a chronic odontogenic infection.
      She presented with perioral swelling with the involvement of bilateral
      submandibular and sublingual areas, accompanied by excruciating pain, chills,
      fever, and vomiting. She was treated with clindamycin and cefoxitin for infection
      and vigorously hydrated. This case is exemplary for the successful management of
      this potentially lethal clinical condition. Our early recognition and aggressive
      treatment helped to prevent complications from Ludwig's angina.

PMID- 29062621
TI  - Rectal Cancer in the Eye: A Case Report of Orbital Metastasis.
AB  - Orbital metastasis from colorectal cancer is extremely rare. In this case report,
      we describe a 48-year-old woman who presented with recurrent severe headaches and
      new onset constipation with no known history of cancer. After vigilant workup,
      imaging, and biopsies, she was diagnosed with orbital metastasis from a primary
      rectal carcinoma. She was started on chemotherapy and radiation therapy. Her
      chemotherapy regimen consisted of FLOX (leucovorin + fluorouracil + oxaliplatin),
      along with panitumumab, which she tolerated well. She received chemotherapy for
      seven months before she lost her battle with cancer.

PMID- 29062622
TI  - Caregiver's Burden of the Patients With Traumatic Brain Injury.
AB  - Insufficient attention towards caregivers has resulted in the emergence of
      psychological and health complaints. Affliction tethers more towards spouses as
      compared to parents and females as compared to males. The role of sibling care
      givers was found to be no different from parents or spouses. Marital
      relationships were found to suffer the most, with the caregiver leaving the
      traumatic brain injury (TBI) patient in his time of need. The Brief Symptom
      Inventory (BSI) and family assessment device (FAD) predicted a correlation
      between patient variables and caregiver discontent. The Blacks/Hispanics proved
      to cope better with stress and their caregiver roles as compared to Whites. Time
      elapsed since the injury was found to relieve distress, while the surprising
      severity of the injury has no recorded impact. Social support or rather a lack of
      it has been seen to have an impact on family homeostasis, which can further be
      deteriorated by substance abuse by the patient. The therapeutic intervention
      found to be most advantageous was the D'Zurilla and Nezu social problem-solving
      model. Current evidence suggests that emphasis should be given on proper
      education and encouragement of caregivers before discharge of TBI patients from
      hospital to reduce the incidence of stressors. Additionally, counseling sessions
      should be led by professionally led support groups for dealing with psychological
      symptoms and peer-led group to eliminate social insecurities of caregivers.

PMID- 29062623
TI  - A Complicated Case of Group B Streptococcus Empyema Necessitans.
AB  - Empyema necessitans is a complication of a pleural space infection that dissects
      through the pleura into the soft tissues of the chest and skin. Due to the
      widespread availability of antibiotics, empyema necessitans is rare in modern
      medicine and is most commonly caused by Mycobacterium tuberculosis. A 38-year-old
      immunocompetent male presented with left shoulder pain and his chest radiograph
      revealed a mass in the upper left lung and/or pleural space. He underwent
      multiple debridements of the chest wall due to a left chest wall abscess and
      empyema necessitans. All operative samples were positive for Streptococcus
      agalactiae (Group B Streptococcus). The patient's clinical course was complicated
      by septic arthritis of the left sternoclavicular joint and first rib, vertebral
      osteomyelitis/discitis, and pelvic abscesses. This case report illustrates the
      pathogenic process of empyema necessitans and summarizes the clinical management
      for practicing clinicians. It also documents the second case of Streptococcus
      agalactiae-associated empyema necessitans, to our knowledge, with significantly
      greater disease extension than the first.

PMID- 29062624
TI  - Interactive Online Learning for Attending Physicians in Ultrasound-guided Central
      Venous Catheter Insertion.
AB  - Evidence has demonstrated that the use of dynamic ultrasound guidance (USG) for
      central venous catheter (CVC) significantly decreases attempts, failures, and
      complication rates. Despite national organizations recommending the use of USG
      and its increasing availability, USG is used inconsistently and non-uniformly. We
      sought to determine if an online training module for CVC insertion with
      ultrasound guidance will improve acquisition and long-term retention of knowledge
      and skills for attending physicians. Participants were tested for declarative
      knowledge and skills on a simulator (pre-test) for ultrasound-guided CVC
      insertion at baseline. They then completed an online learning module followed by
      an immediate post-test and a six-month retention test. There were 16 attending
      physicians who participated in the study. The CVC training module increased
      declarative knowledge acquisition and retention. No significant difference in
      simulated CVC performance was found over the three time points.

PMID- 29062625
TI  - Valproate-Induced Hyperammonemic Encephalopathy.
AB  - Valproate is the best choice drug for a variety of medical conditions. As with
      any other drug, it has adverse effects, and it is important to emphasize the
      possibility of those adverse effects to prevent complications. We present the
      case history of a 44-year-old male with valproate-induced hyperammonemic
      encephalopathy, despite having normal liver function tests. This case includes a
      detailed literature review of this rare adverse event. In the light of this case
      report, we illustrate the importance of checking ammonia levels in all
      psychiatric patients receiving valproate as a treatment who present with new
      onset neurological symptoms or altered mental status.

PMID- 29062626
TI  - Ifosfamide-Induced Malignancy of Ureter and Bladder.
AB  - Cyclophosphamide-induced bladder malignancy is a well-known entity mediated by
      its metabolic product, acrolein. There is a significant association between the
      incidence of hemorrhagic cystitis during treatment and the later development of
      malignancies. We report a case of multifocal urothelial carcinoma occurring in a
      patient treated with ifosfamide 19 years ago. No case report of ifosfamide
      induced malignancy could be identified in the literature. A brief review of the
      literature on the relative risks of ifosfamide therapy, the mechanism of bladder
      toxicity, and suggestions to minimize the deleterious effects of the drug have
      been done. Ifosfamide should be used in the lowest possible dose and that
      patients receiving more than 20 grams of the drug should undergo a routine
      urinalysis for microscopic hematuria. Prophylactic measures such as high fluid
      intake, frequent voiding, day time administration of the drug, and concomitant
      use of mesna may decrease the contact time and the concentrations of toxic
      metabolites on the bladder urothelium.

PMID- 29062627
TI  - Comparison of Mental Health Service Utilization by Asian Americans and Non
      Hispanic Whites versus Their Cardiovascular Care Utilization.
AB  - INTRODUCTION: This study will determine whether racial/ethnic disparities persist
      in various psychiatric disorders among Asian Americans. METHODS: Secondary
      analyses of data from the second largest public health system in the US (total
      N=22294) were performed. Chi-squared statistics were used to compare the race for
      mental health service utilization for five psychiatric diagnoses. Cardiovascular
      care utilization by Asian Americans and non-Hispanic whites was used as a proxy
      for overall healthcare utilization rates between the two racial groups and
      constituted the expected values for the analysis. RESULTS: Asian Americans were
      less likely to utilize mental health services for bipolar disorder,
      schizophrenia, anxiety, depression, and intellectual disabilities. CONCLUSION:
      The results of this study call for ways to increase mental health service
      utilization on par with cardiovascular healthcare utilization among Asian
      Americans.

PMID- 29062628
TI  - Toward Self-Growing Soft Robots Inspired by Plant Roots and Based on Additive
      Manufacturing Technologies.
AB  - In this article, we present a novel class of robots that are able to move by
      growing and building their own structure. In particular, taking inspiration by
      the growing abilities of plant roots, we designed and developed a plant root-like
      robot that creates its body through an additive manufacturing process. Each
      robotic root includes a tubular body, a growing head, and a sensorized tip that
      commands the robot behaviors. The growing head is a customized three-dimensional
      (3D) printer-like system that builds the tubular body of the root in the format
      of circular layers by fusing and depositing a thermoplastic material (i.e.,
      polylactic acid [PLA] filament) at the tip level, thus obtaining movement by
      growing. A differential deposition of the material can create an asymmetry that
      results in curvature of the built structure, providing the possibility of root
      bending to follow or escape from a stimulus or to reach a desired point in space.
      Taking advantage of these characteristics, the robotic roots are able to move
      inside a medium by growing their body. In this article, we describe the design of
      the growing robot together with the modeling of the deposition process and the
      description of the implemented growing movement strategy. Experiments were
      performed in air and in an artificial medium to verify the functionalities and to
      evaluate the robot performance. The results showed that the robotic root, with a
      diameter of 50 mm, grows with a speed of up to 4 mm/min, overcoming medium
      pressure of up to 37 kPa (i.e., it is able to lift up to 6 kg) and bending with a
      minimum radius of 100 mm.

PMID- 29062629
TI  - Smart Braid Feedback for the Closed-Loop Control of Soft Robotic Systems.
AB  - This article experimentally investigates the potential of using flexible,
      inductance-based contraction sensors in the closed-loop motion control of soft
      robots. Accurate motion control remains a highly challenging task for soft
      robotic systems. Precise models of the actuation dynamics and environmental
      interactions are often unavailable. This renders open-loop control impossible,
      while closed-loop control suffers from a lack of suitable feedback. Conventional
      motion sensors, such as linear or rotary encoders, are difficult to adapt to
      robots that lack discrete mechanical joints. The rigid nature of these sensors
      runs contrary to the aspirational benefits of soft systems. As truly soft sensor
      solutions are still in their infancy, motion control of soft robots has so far
      relied on laboratory-based sensing systems such as motion capture,
      electromagnetic (EM) tracking, or Fiber Bragg Gratings. In this article, we used
      embedded flexible sensors known as Smart Braids to sense the contraction of
      McKibben muscles through changes in inductance. We evaluated closed-loop control
      on two systems: a revolute joint and a planar, one degree of freedom continuum
      manipulator. In the revolute joint, our proposed controller compensated for
      elasticity in the actuator connections. The Smart Braid feedback allowed motion
      control with a steady-state root-mean-square (RMS) error of [1.5] degrees . In
      the continuum manipulator, Smart Braid feedback enabled tracking of the desired
      tip angle with a steady-state RMS error of [1.25] degrees . This work
      demonstrates that Smart Braid sensors can provide accurate position feedback in
      closed-loop motion control suitable for field applications of soft robotic
      systems.

PMID- 29062630
TI  - Design of a Variable Stiffness Soft Dexterous Gripper.
AB  - This article presents the design of a variable stiffness, soft, three-fingered
      dexterous gripper. The gripper uses two designs of McKibben muscles. Extensor
      muscles that increase in length when pressurized are used to form the fingers of
      the gripper. Contractor muscles that decrease in length when pressurized are then
      used to apply forces to the fingers through tendons, which cause flexion and
      extension of the fingers. The two types of muscles are arranged to act
      antagonistically and this means that by raising the pressure in all of the
      pneumatic muscles, the stiffness of the system can be increased without a
      resulting change in finger position. The article presents the design of the
      gripper, some basic kinematics to describe its function, and then experimental
      results demonstrating the ability to adjust the bending stiffness of the
      gripper's fingers. It has been demonstrated that the fingers' bending stiffness
      can be increased by more than 150%. The article concludes by demonstrating that
      the fingers can be closed loop position controlled and are able to track step and
      sinusoidal inputs.

PMID- 29062631
TI  - Immediate Nipple-Areolar Complex Reconstruction for Patients Undergoing Implant
      Based Reconstruction or Therapeutic Mammoplasty.
AB  - BACKGROUND: We report a technique of immediate nipple-areolar complex (NAC)
      reconstruction for patients undergoing skin-sparing mastectomy and implant-based
      breast reconstruction or therapeutic mammoplasty with central excision. METHODS:
      Immediate nipple reconstruction is performed using a modified C-V flap planned
      along the edge of the incision. The areola is reconstructed using a full
      thickness skin graft taken from skin usually discarded during the procedure.
      Immediate NAC reconstruction using this technique was performed on 32 breasts in
      21 patients. This included 19 risk-reducing mastectomies, 9 therapeutic
      mastectomies, and 2 major revisions to existing implant reconstruction.
      Reconstruction was direct to implant in 29 breasts and by expander in 1 breast.
      The device was placed in a pre- or post-pectoral plane utilizing dermal sling
      and/or acellular dermal matrix as determined on a case-by-case basis. Immediate
      NAC reconstruction was also performed on 2 patients undergoing therapeutic
      mammoplasty with central excision. RESULTS: Mean follow-up is 12 months (5-27
      months), and cosmetic results have been good. There have been no significant
      complications, and no revisional surgery has been required. CONCLUSION: The
      application of simple techniques for NAC reconstruction in the primary procedure
      allows reconstruction of the whole breast in a single stage. There is an
      immediate focal point to the reconstruction to improve cosmesis, patient
      satisfaction, and psychosocial function without delay.

PMID- 29062632
TI  - Assessment of Aesthetic Results of 100 Patients Who Underwent Rhinoplasty
      Rhinoplasty Outcome Evaluation.
AB  - BACKGROUND: To assess the long-term aesthetic results of rhinoplasty and predict
      the final outcome. METHODS: The sample was composed of 100 patients (34 men and
      66 women) between 23 and 57 years old (mean, 34.8) operated on exclusively for
      aesthetic reasons. The time elapsed from the operation ranged from 3 to 13 years
      with a mean of 6.8 years. The study used Rhinoplasty Outcome Evaluation
      questionnaire, a simple, reliable, validated, and widely used inventory. RESULTS:
      The vast majority of patients (93%) were satisfied postoperatively with scores >
      50% (67 patients had scores > 80%). Only 7 patients had scores less than 50%. The
      mean score was 82.4 +/- 1.7% with a median of 87%. In addition, it seems that the
      results of the operation remain high through time with a small decline along age
      groups and years elapsed. Women were found more satisfied than men (P = 0.03).
      CONCLUSIONS: The study concludes that the results of aesthetic rhinoplasty, if
      performed by skilled and experienced surgeons, are very satisfying and stable
      throughout time.

PMID- 29062634
TI  - Septic Shock following Prostate Biopsy: Aggressive Limb Salvage for Extremities
      after Pressor-Induced Ischemic Gangrene.
AB  - Vasopressors used to treat patients with septic shock can cause ischemic necrosis
      of appendages such as the ears and nose, as well as the extremities. Cases of
      quadruple-extremity necrosis have high morbidity and mortality, and a profound
      negative impact on quality of life. This case report details the successful limb
      salvage and return to function using free tissue transfer as a means to salvage
      bilateral lower extremities in a patient who suffered vasopressor-induced
      ischemia of upper and lower extremities after prostate biopsy-induced septic
      shock. Septic shock following transrectal ultrasound-guided prostate biopsy is a
      rare, yet life-threatening complication. Successful treatment included thorough
      planning and staging of therapies such as awaiting tissue demarcation and serial
      surgical debridement to adequately prepare the tissue bed for free tissue
      transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative
      pressure wound therapy, and meticulous wound care played a crucial role in wound
      healing. This vigilant planning and coordinated care resulted in the successful
      lower extremity salvage, consisting of bilateral transmetatarsal amputations and
      free tissue transfer to both limbs. We present our long-term follow-up of a
      functional ambulatory patient after catastrophic, life-threatening infection and
      appropriate multidisciplinary care.

PMID- 29062633
TI  - Comparative Effectiveness of Needle Aponeurotomy and Collagenase Injection for
      Dupuytren's Contracture: A Multicenter Study.
AB  - BACKGROUND: Although the efficacy of collagenase clostridium histolyticum (CCH)
      injections has been demonstrated by randomized clinical trials, the relative
      effectiveness of CCH remains uncertain. Our aim was to compare the outcomes of
      CCH with those of percutaneous needle aponeurotomy (PNA) in daily clinical
      practice. METHODS: We analyzed data from patients undergoing PNA or CCH between
      2011 and 2014 at 7 practice sites in the Netherlands. We examined the degree of
      improvement in contracture and adverse effects at 6-12 weeks after surgery or the
      last injection. Additionally, we invited patients to complete the Michigan Hand
      Questionnaire before and at 6-12 months follow-up. To minimize the risk of bias,
      we used propensity score matching. RESULTS: Among 130 matched patients (93%
      Tubiana I or II) undergoing PNA (n = 46) and CCH (n = 84), improvement in
      contracture was similar: 26 degrees (65% improvement from baseline) for PNA
      versus 31 degrees (71%) for CCH for affected metacarpophalangeal joints (P =
      0.163). This was 16 degrees (50% improvement) versus 17 degrees (42%) for
      affected proximal interphalangeal joints (P = 0.395), respectively. No serious
      adverse effects occurred in either of the 2 treatment groups. Of the mild adverse
      effects, only skin fissures and sensory disturbances were seen in both groups.
      Through 1-year follow-up, patients reported similar improvements in the overall
      Michigan Hand Questionnaire score (PNA 5.3 points versus CCH 4.9 points; P =
      0.912). CONCLUSIONS: In patients with mild contractures (Tubiana I or II), CCH
      was as effective as PNA in reducing contractures. Both treatments were safe and
      improved hand function to a similar extent in daily practice.

PMID- 29062635
TI  - Capturing Plastic Surgery on Film-Making Reconstruction Visible.
AB  - The Swiss Plastic Surgery Association (https://plasticsurgery.ch/en/) decided to
      produce a corporate video to illustrate the concept of "plastic surgery of
      confidence" to the public. We show the diversity of specializations and the vast
      range of tasks that surgeons passionately handle day in and day out. We wanted to
      convey 2 main messages: first, that plastic surgery is more than just cosmetic
      surgery, and second, that plastic surgery in Switzerland is synonymous with
      quality and confidence. We selected 17 topics that we felt had good filmic
      potential and would best explain to the public what plastic surgery is about.
      This included the selection of appropriate patients, experts, and locations from
      all over the country. We thought it crucial to show the initial preoperative
      situation, as only in this case would the achievement of reconstruction be
      evident and comprehensive to the layman audience. The actual production was
      filmed in 5 different locations and took 5 days of shooting. We recorded 17
      surgeons, 9 patients, and about 30 voluntary background actors. From 23 hours of
      footage, we created a 7 minute, 22 second corporate video, recorded in 3 of the
      Swiss national languages. The video was presented to the public online in June
      2016, on the same day as the National Open Day of Plastic Surgery in Switzerland.
      The video is available online. We evaluated the impact of the video using a
      questionnaire for lay people and observed that it could substantially improve the
      perception of our specialty, especially regarding the reconstructive aspect. We
      feel that a freely available corporate video is a very useful means to promote
      plastic surgery and help patients better understand what it is all about.

PMID- 29062637
TI  - Visualization of Skin Perfusion by Indocyanine Green Fluorescence Angiography-A
      Feasibility Study.
AB  - Plastic and reconstructive surgery relies on the knowledge of angiosomes in the
      raising of microsurgical flaps. Growing interest in muscle-sparing perforator
      flaps calls for reliable methods to assess the clinical feasibility of new donor
      sites in anatomical studies. Several injection techniques are known for the
      evaluation of vascular territories. Indocyanine green-based fluorescence
      angiography has found wide application in the clinical assessment of tissue
      perfusion. In this article, the use of indocyanine green-based fluorescence
      angiography for the assessment of perforasomes in anatomical studies is described
      for the first time.

PMID- 29062638
TI  - End-to-End Lymphaticovenular Anastomosis Does Not Disturb the Contraction of
      Collecting Lymph Vessels.
AB  - Supplemental Digital Content is available in the text.

PMID- 29062639
TI  - Anatomic Variations of the Median Nerve Identified during Endoscopic Carpal
      Tunnel Release with STRATOS.
AB  - Supplemental Digital Content is available in the text.

PMID- 29062636
TI  - Blood Supply to the Integument of the Abdomen of the Rat: A Surgical Perspective.
AB  - BACKGROUND: Many fundamental questions regarding the blood supply to the
      integument of the rat remain to be clarified, namely the degree of homology
      between rat and humans. The aim of this work was to characterize in detail the
      macro and microvascular blood supply to the integument covering the ventrolateral
      aspect of the abdominal wall of the rat. METHODS: Two hundred five Wistar male
      rats weighing 250-350 g were used. They were submitted to gross anatomical
      dissection after intravascular colored latex injection (n = 30); conversion in
      modified Spalteholz cleared specimens (n=10); intravascular injection of a
      Perspex solution, and then corroded, in order to produce vascular corrosion casts
      of the vessels in the region (n = 5); histological studies (n = 20); scanning
      electron microscopy of vascular corrosion casts (n = 10); surgical dissection of
      the superficial caudal epigastric vessels (n = 100); and to thermographic
      evaluation (n = 30). RESULTS: The ventrolateral abdominal wall presented a
      dominant superficial vascular system, which was composed mainly of branches from
      the superficial caudal epigastric artery and vein in the caudal half. The cranial
      half still received significant arterial contributions from the lateral thoracic
      artery in all cases and from large perforators coming from the intercostal
      arteries and from the deep cranial epigastric artery. CONCLUSIONS: These data
      show that rats and humans present a great deal of homology regarding the blood
      supply to the ventrolateral aspect of the abdominal integument. However, there
      are also significant differences that must be taken into consideration when
      performing and interpreting experimental procedures in rats.

PMID- 29062640
TI  - 10 Years Later: Lessons Learned from an Academic Multidisciplinary Cosmetic
      Center.
AB  - BACKGROUND: In 2006, a Centers for Medicare and Medicaid Services-accredited
      multidisciplinary academic ambulatory surgery center was established with the
      goal of delivering high-quality, efficient reconstructive, and cosmetic services
      in an academic setting. We review our decade-long experience since its
      establishment. METHODS: Clinical and financial data from 2006 to 2016 are
      reviewed. All cosmetic procedures, including both minimally invasive and
      operative cases, are included. Data are compared to nationally published reports.
      RESULTS: Nearly 3,500 cosmetic surgeries and 10,000 minimally invasive procedures
      were performed. Compared with national averages, surgical volume in
      abdominoplasty is high, whereas rhinoplasty and breast augmentation is low.
      Regarding trend data, breast augmentation volume has decreased by 25%, whereas
      minimally invasive procedural volume continues to grow and is comparable with
      national reports. Similarly, where surgical revenue remains steady, minimally
      invasive revenue has increased significantly. The majority of surgical cases
      (70%) are reconstructive in nature and insurance-based. Payer mix is 71% private
      insurance, 18% Medicare and Medicaid, and 11% self-pay. Despite year-over-year
      revenue increases, net profit in 2015 was $6,120. Rent and anesthesia costs
      exceed national averages, and employee salary and wages are the highest
      expenditure. CONCLUSION: Although the creation of our academic cosmetic
      ambulatory surgery center has greatly increased the overall volume of cosmetic
      surgery performed at the University of Wisconsin, the majority of surgical volume
      and revenue is reconstructive. As is seen nationwide, minimally invasive cosmetic
      procedures represent our most rapidly expanding revenue stream.

PMID- 29062641
TI  - Evaluation of 4 Outcomes Measures in Microtia Treatment: Exposures, Infections,
      Aesthetics, and Psychosocial Ramifications.
AB  - BACKGROUND: In craniofacial microsomia, microtia and canal atresia pose
      formidable reconstructive challenges. We review our institutional experience in
      treating microtia and atresia to identify variables associated with 4 outcomes
      measures: complications, surgical revisions, aesthetic outcomes, and psychosocial
      function. METHODS: Craniofacial microsomia patients treated at the University of
      California Los Angeles Craniofacial Clinic between 2008 and 2014 greater than 13
      years of age (n = 68) were reviewed for microtia and atresia treatment and
      outcomes. RESULTS: In total, 91.2% of patients diagnosed with craniofacial
      microsomia presented with microtia, affecting 75 ears. Both a male and right
      sided predominance were observed. Fifty-six patients (90.3%) underwent autologous
      external ear reconstruction at an average age of 8.5 years. Age, type of
      incision, and size of cartilage framework did not predict total number of
      surgeries or complications. Severity of ear anomalies correlated with increased
      number of surgeries (P < 0.001) and decreased aesthetic outcomes (P < 0.001) but
      not complications. In total, 87.1% of patients with microtia had documented
      hearing loss, of which the majority were conductive and 18.5% were mixed
      sensorineural and conductive. Hearing deficits were addressed in 70.4% of
      patients with external hearing aids, bone anchored hearing aids, or canaloplasty.
      Of all variables, improvement of psychosocial function was correlated only to
      hearing loss treatment of any type (P = 0.01). CONCLUSIONS: On evaluation of
      surgical and patient characteristics, severity of microtia predicted the total
      number of surgical revisions performed and aesthetic ratings. In addition, we
      found that the only factor that correlated with improved patient and parent
      reported psychosocial outcomes was treatment of hearing loss.

PMID- 29062642
TI  - Breast Reduction: Decreasing Complications and Improving Long-Term Aesthetic
      Results with Parenchymal Sutures.
AB  - BACKGROUND: The inverted T/keyhole pattern is commonly used for large breast
      reductions. This technique relies on the breast skin to retain the shape. With
      the passage of time "fallout" (pseudoptosis) occurs impairing the cosmetic
      result. A technique is described that uses parenchymal sutures and inframammary
      fold (IMF) reinforcement sutures to maintain the intraoperative shape. METHODS: A
      retrospective study of 25 consecutive patients (50 breasts) where the IMF was
      reinforced and parenchymal sutures were inserted. The patients were followed up
      and the nipple to notch and nipple to IMF distance was measured and compared with
      that marked preoperatively and set intraoperatively. Complications, especially T
      junction breakdown, were also recorded. RESULTS: The mean age was 38 years
      (range, 16-62 years) with a mean follow-up of 12 months. The mean body mass index
      was 31 (range, 22-41). The mean mass of tissue excised was 925 g (range, 340
      1,800 g) per side. The distance from the suprasternal notch to the nipple
      remained unchanged. The distance from the nipple to the IMF remained the same as
      that marked preoperatively except in 3 patients who developed pseudoptosis. Only
      3 patients had wound dehiscence. CONCLUSION: Parenchymal and superficial fascial
      system sutures combined with IMF reinforcement contributes to maintaining the
      aesthetic result and decreasing complications, in weight stable patients.

PMID- 29062643
TI  - Mycobacterium avium Infection after Acupoint Embedding Therapy.
AB  - Nontuberculous mycobacterium is a ubiquitous environmental organism that is
      unusual to cause a true infection, but it can cause severe cutaneous infections.
      In this case report, we present a successful treatment for a Chinese patient with
      Mycobacterium avium cutaneous infection after acupoint embedding therapy. We
      managed to conduct pathogenic detection, drug sensitive test, and
      multidisciplinary consultation. Finally, a systematic treatment strategy of
      nontuberculous mycobacterium was performed. Twenty-two-month follow-up revealed
      excellent outcome without any recurrence.

PMID- 29062644
TI  - Validation of a Unilateral Cleft Lip Surgical Outcomes Evaluation Scale for
      Surgeons and Laypersons.
AB  - BACKGROUND: A standardized evaluation tool is needed for the assessment of
      surgical outcomes in cleft lip surgery. Current scales for evaluating unilateral
      cleft lip/nose (UCL/N) aesthetic outcomes are limited in their reliability, ease
      of use, and application. The Unilateral Cleft Lip Surgical Outcomes Evaluation
      (UCL SOE) scale measures symmetry of 4 components and sums these for a total
      score. The purpose of this study was to validate the SOE as a reliable tool for
      use by both surgeons and laypersons. METHODS: Twenty participants (9 surgeons and
      12 laypeople) used the SOE to evaluate 25 sets of randomly selected presurgical
      and postsurgical standardized photographs of UCL/N patients. Interrater
      reliability for surgeon and laypeople was determined using an intraclass
      correlation coefficient (ICC). RESULTS: Individual surgeons and laypeople both
      reached an ICC in the "fair to good" range (ICC = 0.42 and 0.59, respectively).
      Averaging 2 evaluators in the surgeon group improved the ICC to 0.58 and in the
      laypeople group to 0.74, respectively. Averaging 3 evaluators increased the ICC
      for surgeons to the "good" range (ICC = 0.71) and the ICC for laypeople to the
      "very good" range (ICC = 0.82). CONCLUSIONS: Surgeon and layperson raters can
      reliably use the SOE to assess the aesthetics results after surgical repair of
      UCL/N, and improved reliability and reproducibility is achieved by averaging the
      scores of multiple reviewers.

PMID- 29062645
TI  - A Technique for Reduction of Edentulous Fractures Using Dentures and SMARTLock
      Hybrid Fixation System.
AB  - Establishing anatomic reduction of an edentulous mandible fracture is a
      frequently acknowledged challenge in craniomaxillofacial trauma surgery. In this
      study, we report a novel method for the reduction of the edentulous mandible
      fracture, via fabrication of modified Gunning splints using existing dentures and
      SMARTLock hybrid arch bars. This technique dramatically simplifies the
      application of an arch bar to dentures, obviates the need for the fabrication of
      impressions and custom splints, and eliminates the lag time associated with the
      creation of splints. Furthermore, this method may be used with or without
      adjunctive rigid internal fixation. The technique described herein of creating
      Gunning splints with SMARTLock hybrid arch bars provides surgeons with a simple,
      rapid, single-stage solution for reduction of mandibular fractures in the
      edentulous patient.

PMID- 29062646
TI  - Calcium Hydroxylapatite Combined with Microneedling and Ascorbic Acid is
      Effective for Treating Stretch Marks.
AB  - BACKGROUND: Stretch marks can have a negative psychological impact on some
      individuals. Methods are available for treating stretch marks, but high-quality
      evidence supporting their use is limited. We treat stretch marks using injections
      of diluted calcium hydroxylapatite (CaHA, Radiesse) filler combined with
      microneedling and topical ascorbic acid. This retrospective study evaluated the
      effectiveness of this combined therapy. METHODS: Subjects presented with red (n =
      25) or white (n = 10) striae on their buttocks, thighs, knees, abdomen, and
      breasts. CaHA filler was diluted 1:1 with lidocaine 2% without epinephrine. A
      maximum of 3.0 mL of filler was injected per patient at all skin depths using a
      23G needle. This was immediately followed by microneedling and topical
      application of 20% ascorbic acid. Microneedling with ascorbic acid was repeated
      after 1 and 2 months. Skin biopsies were obtained from a patient who later
      underwent abdominoplasty. RESULTS: The mean (+/-SD) pretreatment Manchester Scar
      Scale scores were 12.0 (+/-0.8), decreasing to 7.1 (+/-1.4) 1 month after the
      final treatment, indicating improvement in stretch mark appearance (P < 0.001).
      Subjects were very satisfied (n = 22; 62.9%), satisfied (n = 8; 22.9%), neither
      satisfied nor dissatisfied (n = 4; 11.4%), or unsatisfied (n = 1; 2.8%) with
      their treatment results. Analysis revealed a significant correlation between Scar
      Scale scores and Patient Satisfaction scores (r = 0.483; P = 0.003). Skin
      biopsies showed increased quantity and quality of collagen and elastin fibers in
      areas treated with combination therapy. Procedures were well tolerated.
      CONCLUSION: Combining 1:1 diluted CaHA with microneedling and topical ascorbic is
      safe and effective for treating stretch marks.

PMID- 29062647
TI  - Anatomical Study of Perfusion of a Periosteal Flap with a Lateral Pedicle.
AB  - BACKGROUND: Pedicled periosteal flaps are commonly used for tissue defects
      between the base of the skull and the midfacial area. This study aimed to clarify
      the 3-dimensional vascular distribution of temporal region flaps. METHODS: Ten
      fresh cadavers were used. Full-thickness cranial flaps were elevated from the
      cranial bone and each layer was detached separately. Contrast enhancement of the
      full thickness of the scalp, macroscopic evaluation, and histologic analyses were
      performed. Radiographs were obtained and image analysis was performed using a 3
      dimensional monitor. RESULTS: The mean number of deep vessels extending from the
      parietal branch of the superficial temporal artery was 68.7, including 14.2 and
      54.5 vessels on the proximal and distal sides, respectively. The mean number of
      deep vessels extending from the frontal branch of the superficial temporal artery
      was 71.6, including 17.6 and 54.0 vessels on the proximal and distal sides,
      respectively. There were significantly more perforating branches in the distal
      area than in the proximal area of both the frontal and parietal branches (P =
      0.005). There was no significant difference in the number of perforating branches
      between the frontal and parietal branches. CONCLUSIONS: Contrast-enhanced images
      of the loose areolar tissue and periosteal layers revealed vessels that extended
      radially. We successfully identified the 3-dimensional structure of the
      perforating vessels peripheral to the temporal fossa. Our findings provide a
      theoretical foundation for the feasibility of elevating a periosteal/loose
      areolar tissue flap with a reliable blood supply without sacrificing the temporal
      muscle.

PMID- 29062648
TI  - Validation of the Unilateral Cleft Lip Severity Index for Surgeons and
      Laypersons.
AB  - BACKGROUND: Severity of the primary unilateral cleft lip/nose deformity (UCL/N)
      is postulated to play a key role in postoperative complications, aesthetic
      result, and need for secondary surgery. There is no validated and widely accepted
      classification scheme of initial cleft severity. The purpose of this study was to
      validate the Unilateral Cleft Lip Cleft Severity Index as a reliable tool for
      evaluating presurgical UCL/N deformity by both surgeons and laypersons. METHODS:
      Twenty-five participants (10 surgeons and 15 laypeople) evaluated 25 sets of
      randomly selected presurgical standardized photographs of UCL/N patients. Each
      participant rated patients on a scale of 1-4 using the Cleft Severity Index.
      Interrater reliability for surgeons, laypersons, and all participants was
      determined using an intraclass correlation coefficient. Histograms and regression
      analysis were performed to compare average ratings between groups. RESULTS:
      Interrater reliability for all groups was classified as "very good" determined by
      intraclass correlation coefficients of 0.837 (laymen), 0.885 (surgeons), and
      0.848 (all participants). These results indicate that there was a high degree of
      interrater across all 3 groups and that both surgeons and laypersons can
      reliability rate cleft severity using the Cleft Severity Index. CONCLUSIONS: This
      study validates the use of the Cleft Severity Index by both surgeons and
      laypersons as a reliable tool for evaluating the degree of presurgical severity
      of patients with UCL/N. The Unilateral Cleft Lip Cleft Severity Index can thus
      serve as a reproducible and reliable grading system for primary UCL/N deformity
      and to categorize patients for future outcomes studies.

PMID- 29062649
TI  - Multimodal Analgesia in Breast Surgical Procedures: Technical and Pharmacological
      Considerations for Liposomal Bupivacaine Use.
AB  - Enhanced recovery after surgery is a multidisciplinary perioperative clinical
      pathway that uses evidence-based interventions to improve the patient experience
      as well as increase satisfaction, reduce costs, mitigate the surgical stress
      response, accelerate functional recovery, and decrease perioperative
      complications. One of the most important elements of enhanced recovery pathways
      is multimodal pain management. Herein, aspects relating to multimodal analgesia
      following breast surgical procedures are discussed with the understanding that
      treatment decisions should be individualized and guided by sound clinical
      judgment. A review of liposomal bupivacaine, a prolonged-release formulation of
      bupivacaine, in the management of postoperative pain following breast surgical
      procedures is presented, and technical guidance regarding optimal administration
      of liposomal bupivacaine is provided.

PMID- 29062650
TI  - Corrected Cephalometric Analysis to Determine the Distance and Vector of
      Distraction Osteogenesis for Syndromic Craniosynostosis.
AB  - BACKGROUND: The purpose of this study was to confirm the utility of a corrected
      cephalometric analysis to facilitate the planning of distraction osteogenesis
      with Le Fort III osteotomy for syndromic craniosynostosis. METHODS: This
      prospective study involved 4 male and 2 female patients (mean patient age, 8
      years 9 months; age range, 4 years 6 months to 13 years 2 months) with Crouzon
      syndrome who were treated with Le Fort III maxillary distraction using our
      previously described system of analysis of a corrected cephalogram and who
      underwent clinical follow-up. Lateral cephalograms were obtained immediately
      after device removal. RESULTS: Distraction of orbitale moved the vector downward
      to the adult profile, but there was slightly less elongation than the adult
      profile for the distraction distance. The desired and real mean angles after
      distraction of point A were 29.2 +/- 7.9 degrees  and 6.1 +/- 8.5 degrees ,
      respectively, and the desired and the real mean distances after distraction of
      point A were 30.6 +/- 12.7 mm and 29.4 +/- 4.1 mm, respectively. CONCLUSIONS:
      Using the corrected cephalometric analysis, the distance and vector of
      distraction osteogenesis with Le Fort III osteotomy could be determined in
      patients with syndromic craniosynostosis. The distraction system brought the
      patients' facial bones to the planned position using controlling devices.

PMID- 29062651
TI  - Underestimating Implant Volumes in Cosmetic Breast Augmentation.

PMID- 29062652
TI  - Repairing Bronchoesophageal Tube Fistula Using A Contralateral Latissimus Dorsi
      Musculocutaneous Flap.
AB  - A postoperative aerodigestive fistula is one of the rare but critical
      complications after esophagectomy, and management is challenging. The essential
      keys to successful treatment of these fistula are thorough debridement and
      complete closure followed by separation of the respiratory and digestive tract.
      We present a case of a recurrent bronchoesophageal fistula between the left main
      bronchus and neo esophagus, which was successfully treated through a
      contralateral approach. The fistula was debrided and closed primarily through a
      right thoracotomy, and the interposition of a pedicled latissimus dorsi
      musculocutaneous flap from the right side was carried out. The patient was able
      to resume oral feeding at 16th postoperative day.

PMID- 29062653
TI  - ASCOT: Autologous Bone Marrow Stem Cell Use for Osteoarthritis of the Thumb-First
      Carpometacarpal Joint.
AB  - BACKGROUND: The first carpometacarpal joint (CMCJ) in the hand is a commonly
      affected joint by osteoarthritis. It causes significant thumb base pain, limiting
      functional capacity. Microfracturing and application of autologous stem cells has
      been performed on large joints such as the knee but has never been evaluated for
      use in the smaller joints in the hand. Our aim was to determine the potential
      benefit of microfracturing and autologous bone marrow stem cells for treatment of
      osteoarthritis of the first CMCJ in the hand. METHODS: All inclusion criteria
      were satisfied. Preoperative assessment by the surgeon, physiotherapist, and
      occupational therapist was performed. The first CMCJ was microfractured and the
      Bone Marrow Stem Cells were applied directly. Postoperatively, the patients were
      followed up for 1 year. RESULTS: Fifteen patients met inclusion criteria;
      however, 2 patients were excluded due to postoperative cellulitis and diagnosis
      of De Quervain's tenosynovitis. The mean scores of the 13-patient preoperative
      and 1 year follow-up assessments are visual analog score at rest of 3.23-1.69 (P
      = 0.0292), visual analog score on activity of 7.92-4.23 (P = 0.0019), range of
      motion 45.77o-55.15o (P = 0.0195), thumb opposition score 7.62-9.23 (P = 0.0154),
      Disability of the Arm, Shoulder and Hand score of 51.67-23.08 (P = 0.0065).
      Strength improved insignificantly from 4.7 kg preoperatively to 5.53 kg at 12
      months (P = 0.1257). All patients had a positive Grind test preoperatively and a
      negative test after 12 months. CONCLUSIONS: This innovative pilot study is a new
      approach to osteoarthritis of the thumb.

PMID- 29062654
TI  - Autoimmune Syndrome Induced by Adjuvants (ASIA) after Silicone Breast
      Augmentation Surgery.
AB  - Generally, the main complications of silicone implantation are local symptoms.
      However, some patients develop late-onset systemic symptoms often associated with
      a rare form of hyperactive immune response, as part of a syndrome known as
      autoimmune syndrome induced by adjuvants (ASIA). Reported cases of ASIA have
      shown resolution with explantation, but not with immunomodulatory therapy. In
      this report, we described a case of a previously healthy 23-year-old woman, who
      has undergone silicone breast implant augmentation, for aesthetic reasons, and
      developed localized cutaneous impairment 3 years postsurgery. She received a
      diagnosis of ASIA with a new presentation: Lupus-like manifestation through
      localized cutaneous impairment. This patient's symptoms were managed without the
      need for surgical intervention, which has not been previously reported, because
      the patient did not want an explantation for aesthetic reasons. The patient was
      started on hydroxychloroquine, 400 mg per day, and remains asymptomatic after 2
      years of treatment. The exact predisposition to ASIA is still unknown. Without
      implant explantation and with immunomodulatory treatment, this patient's
      condition substantially improved. Based on our current understanding of this
      disease, it might not be prudent to indicate breast augmentation with silicone
      implants in patients with documented autoimmune reaction to an adjuvant, an
      established autoimmune condition, or genetic predisposition. However, if a
      patient does develop silicone-induced ASIA, explantation is no longer the only
      successfully reported option, as these symptoms can be managed with immune
      suppression.

PMID- 29062655
TI  - Prepectoral Implant-Based Breast Reconstruction.
AB  - BACKGROUND: The development of acellular dermal matrices (ADMs) has facilitated
      single-stage implant breast reconstruction (IBR) following skin-sparing
      mastectomy. The conventional approach of postpectoral implant placement with
      lower pole ADM confers a good cosmetic result by improving lower pole projection
      and control, while minimizing issues of implant visibility, palpability, and
      rippling. This is balanced with potential disadvantages including pain,
      disruption of pectoral muscle function, and animation. We report the results of a
      prospective study of prepectoral IBR with total ADM coverage. METHODS:
      Prepectoral IBR with total ADM coverage was performed in 106 patients (166
      breasts) in our institution from 2013 to 2017. The cohort included patients
      undergoing immediate IBR (113 breasts) and revision of existing submuscular IBR
      (53 breasts). Patient demographics, surgical complications, and outcomes from a
      prospective database were analyzed. RESULTS: At a mean follow-up of 485 days,
      patient satisfaction and cosmetic outcomes have been good, with no significant
      capsular contractures or animation deformity. Minor complications including
      delayed healing, red breast, or seroma occurred in 14 breasts (8.4%). Major
      complications including necrosis and implant loss occurred in 5 breasts (3
      patients), with a total explantation rate of 3%. No patients required more than
      an overnight stay in hospital, and there were no delays to adjuvant treatment in
      therapeutic cases. CONCLUSION: Prepectoral implant placement with ADM cover is
      emerging as an alternative approach for IBR. This method facilitates breast
      reconstruction with a good cosmetic outcome for patients who want a quick
      recovery without potential compromise of pectoral muscle function and associated
      problems.

PMID- 29062657
TI  - Optimizing Nipple Position following Nipple-Sparing Mastectomy.
AB  - BACKGROUND: The best treatment for nipple malposition following nipple-sparing
      mastectomy is prevention. This article reviews basic elements for success in
      nipple-sparing mastectomy and offers an option to patients with grade 2-3 breast
      ptosis who strongly desire to preserve the nipple. METHODS: Retrospective review
      identified patients undergoing nipple-sparing mastectomy and immediate
      reconstruction. RESULTS: Patient selection centered on realistic goals for
      postoperative breast size, nipple position, and when not to save the nipple. The
      choice of device considered projection and nipple centralization as equal
      components and led to wider, lower profile devices selectively for the first
      stage of reconstruction. In severe grade 2-3 nipple ptosis, an inferior vertical
      incision or wedge excision was used to enhance nipple position postoperatively.
      Eighteen consecutive patients underwent 32 implant-based breast reconstructions
      following nipple-sparing mastectomy with the vertical incision. The average age
      was 45 years old, and the average body mass index was 26.7. Direct-to-implant
      reconstruction was performed in 25%, whereas 75% had tissue expander-implant
      reconstruction. Overall complications included infection (3%) and nipple necrosis
      (3%) leading to explant in 1 reconstruction. CONCLUSIONS: The final nipple
      position following nipple-sparing mastectomy can be optimized with preoperative
      planning. The vertical incision, combined with proper patient selection and
      choice of device, may increase eligibility for nipple-sparing procedures in
      patients with grade 2-3 ptosis who desire nipple preservation.

PMID- 29062656
TI  - Two-Stage Prosthetic Breast Reconstruction after Mastectomy with or without Prior
      Postmastectomy Radiotherapy.
AB  - BACKGROUND: Two-stage prosthetic breast reconstruction with initial insertion of
      a tissue expander followed by an implant after a period of inflation is a well
      established breast reconstruction option. Most of the current literature
      concentrates on the immediate setting, and there are only a few reports into
      delayed cases, especially after postmastectomy radiotherapy (RT). We performed a
      retrospective review of our experience over a 12.5-year period. METHODS: Between
      June 1998 and December 2010, a total of 671 patients received prosthetic-only
      breast reconstruction. Of these, 170 (25.3%) underwent delayed 2-stage prosthetic
      breast reconstruction after mastectomy for cancer. Patients were divided into
      group A, no postmastectomy RT (n = 150), and group B, postmastectomy RT (n = 20).
      The primary factor examined was the failure of the reconstruction from loss of
      prosthesis with or without smoking. Other complications, as well as rates of
      revisional surgery were also recorded. RESULTS: Expander or implant loss occurred
      in 3 of 150 patients in group A (2.0%) and 3 of 20 patients in group B (15%; P =
      0.02). For nonsmokers, implant loss was 1.6% and 5.6%, respectively (P = NS).
      Smoking was associated with 1 of the 3 losses in group A and 2 of the 3 in group
      B (smokers, n = 2; P < 0.01). There was no significant difference in other
      complications such as seromas or minor wound infections. CONCLUSIONS: Delayed 2
      stage prosthetic breast reconstruction has a low failure rate. It can also be
      successfully completed in selected patients after postmastectomy RT, but care
      must be taken with patients who smoke.

PMID- 29062658
TI  - Cosmetic Surgery Training in Plastic Surgery Residency Programs.
AB  - BACKGROUND: Over the past decade, plastic surgery programs have continued to
      evolve with the addition of 1 year of training, increase in the minimum number of
      required aesthetic cases, and the gradual replacement of independent positions
      with integrated ones. To evaluate the impact of these changes on aesthetic
      training, a survey was sent to residents and program directors. METHODS: A 37
      question survey was sent to plastic surgery residents at all Accreditation
      Council for Graduate Medical Education-approved plastic surgery training programs
      in the United States. A 13 question survey was sent to the program directors at
      the same institutions. Both surveys were analyzed to determine the duration of
      training and comfort level with cosmetic procedures. RESULTS: Eighty-three
      residents (10%) and 11 program directors (11%) completed the survey. Ninety-four
      percentage of residents had a dedicated cosmetic surgery rotation (an increase
      from 68% in 2015) in addition to a resident cosmetic clinic. Twenty percentage of
      senior residents felt they would need an aesthetic surgery fellowship to practice
      cosmetic surgery compared with 31% in 2015. Integrated chief residents were more
      comfortable performing cosmetic surgery cases compared with independent chief
      residents. Senior residents continue to have poor confidence with facial
      aesthetic and body contouring procedures. CONCLUSIONS: There is an increase in
      dedicated cosmetic surgery rotations and fewer residents believe they need a
      fellowship to practice cosmetic surgery. However, the comfort level of performing
      facial aesthetic and body contouring procedures remains low particularly among
      independent residents.

PMID- 29062659
TI  - Bilateral Free Flap Breast Reconstruction Outcomes: Do Abdominal Scars Affect
      Bilateral Flaps?
AB  - BACKGROUND: The incidence of bilateral mastectomies is increasing along with the
      rates of breast reconstructions. A substantial number of patients will present
      with abdominal scars after Cesarean section, laparoscopy, laparotomy, and so on.
      The aim of this study was to evaluate the impact of prior abdominal scars on
      complication rates in abdominal bilateral free flap breast reconstruction.
      METHODS: All consecutive patients with autologous free flap breast reconstruction
      between 2007 and 2014 were eligible. The relevant demographic and clinical data
      were prospectively collected into a study-specific database. Complications and
      reoperations were prospectively registered after postoperative outpatient visits.
      RESULTS: Overall, 493 patients underwent abdominally based breast reconstruction
      during the study period: unilateral (n = 250; 50.7%) or bilateral (n = 243;
      49.3%). In the bilateral group, the abdominal scar locations were Pfannenstiel (n
      = 73; 30.1%), midline (n = 16; 6.6%), lower oblique (n = 17; 7.0%), upper oblique
      (n = 5; 2.1%), and laparoscopic (n = 69; 28.4%). Four (1.7%) flap failures
      (including 1 converted to a pedicled transverse rectus abdominis flap) were
      registered, all occurring in patients from the scar group: 3 with Pfannenstiel
      incision and 1 patient with prior laparoscopy. Pfannenstiel scar was associated
      with higher risk of hematoma at the recipient site when compared with no scar
      group (13.7% versus 2.2%; P = 0.006). Partial flap necrosis, infection, and
      seroma occurred in 14 (5.9%), 8 (3.4%), and 5 (2.1%) patients, respectively, and
      no differences between the scar groups were identified. CONCLUSION: Surgical
      outcomes of bilateral reconstructions in patients with abdominal scars are
      generally comparable with ones in patients without prior surgery; however, some
      problems have been identified. These procedures might have some intraoperative
      considerations and often require increased operative times. Apart from the
      traditional preoperative computed tomography angiography, intraoperative imaging
      (e.g., fluorescence angiography) may be advocated in patients with abdominal
      scars.

PMID- 29062660
TI  - Scar Tissue Causing Saphenous Nerve Entrapment: Percutaneous Scar Release and Fat
      Grafting.
AB  - Painful neuropathies can be caused by nerve compression or neuromas. Nerve
      compressions can arise from scar adhesions causing painful posttraumatic
      entrapment of nerve branches via fibrosis. The classical treatment methods
      include neurolysis and nerve transposition. In this case, we present the
      treatment of recurrent scar entrapment of the saphenous nerve with percutaneous
      neurolysis and lipofilling in a patient who had previously undergone an open
      neurolysis procedure. Resolution of the condition without any complications was
      noted during the 2-month clinical follow-up. Percutaneous neurolysis and
      lipofilling are shown to be safe and reproducible methods for the treatment of
      neuropathic compressive scars.

PMID- 29062661
TI  - Novel Double-Needle System That Can Prevent Intravascular Injection of Any
      Filler.
AB  - A new type of needle system combines 2 parts, an inner needle and an outer
      needle. The inner needle is used for filler injection and the outer needle acts
      as a guiding needle that can observe blood reflow when inserting into the vessel
      lumen during injection process. This new needle system can be used for all kinds
      of filler, providing real time monitoring for physician and preventing
      intravascular injection of any filler.

PMID- 29062663
TI  - Free Neurovascular Latissimus Dorsi Muscle Transplantation for Reconstruction of
      Hip Abductors.
AB  - Resection of tumors affecting the hip abductors can cause significant decrease in
      muscle strength and may lead to abnormal gait and poor function. We present a
      case report showing full functional recovery after resection of a synovial
      sarcoma affecting the right gluteus medius and minimus muscles with
      reconstruction free neurovascular latissimus dorsi muscle transplantation. The
      latissimus dorsi muscle was harvested following standard technique and fixed to
      the ilium and the greater trochanter. Receptor vessels were end-to-end
      anastomosed to the subscapular vessels followed by an end-to-end epineural suture
      between the superior gluteal nerve and the thoracodorsal nerve. A year after
      surgery, there is no evidence of recurrent disease; electromyographic analysis
      shows complete reinnervation of the latissimus dorsi muscle flap, and the patient
      has achieved full functional recovery. Free functional latisimus dorsi transfer
      could be considered as a viable reconstruction technique after hip abductors
      resection in tumor surgery.

PMID- 29062664
TI  - Combined Gluteus and Pudendal Thigh Flap Reconstruction of Vaginal Defects
      following Robotic Abdominoperineal Resection.
AB  - Low-lying rectal cancers are being treated more frequently with robotic-assisted
      abdominoperineal resection, obviating the need for laparotomy and the ability to
      raise vertical rectus abdominis musculocutaneous flaps. For female patients,
      posterior vaginectomy often accompanies the resection. Combined pudendal thigh
      flaps as an extension of bilateral gluteus advancement flaps allow for posterior
      vaginal resurfacing with thin pliable fasciocutaneous flaps, which rest on the
      gluteal flap soft-tissue bulk that obliterates the pelvic dead space. For
      patients with advanced cancers who have had neoadjuvant chemoradiation, the
      pudendal skin paddle can be planned more laterally to bring in healthier medial
      thigh skin. The donor incisions lie within the gluteal cleft and crease and groin
      creases recapitulating normal perineal anatomy and aesthetics.

PMID- 29062662
TI  - Hyperbaric Oxygen Inhibits Reperfusion-Induced Neutrophil Polarization and
      Adhesion Via Plasmin-Mediated VEGF Release.
AB  - BACKGROUND: Ischemia-reperfusion (IR) injury is seen in many settings such as
      free flap salvage and limb replantation/revascularization. The consequences
      partial/total flap loss, functional muscle loss, or amputation-can be
      devastating. Of the treatment options available for IR injury, hyperbaric oxygen
      (HBO) is the most beneficial. HBO inhibits neutrophil-endothelial adhesion
      through interference of CD18 neutrophil polarization in IR, a process mediated by
      nitric oxide. The purposes of this study were to examine the involvement of
      vascular endothelial growth factor (VEGF) in the beneficial HBO effect on CD18
      polarization and neutrophil adhesion and investigate the effect of plasmin on
      VEGF expression in skeletal muscle following IR injury. METHODS: A rat gracilis
      muscle model of IR injury was used to evaluate the effect of VEGF in IR, with and
      without HBO, on neutrophil CD18 polarization and adhesion in vivo and ex vivo.
      Furthermore, we investigated the effects that plasmin has on VEGF expression in
      gracilis muscle and pulmonary tissue by blocking its activation with alpha-2
      antiplasmin. RESULTS: HBO treatment following IR injury significantly decreased
      neutrophil polarization and adhesion ex vivo compared with the IR group. Anti
      VEGF reversed the beneficial HBO effect after IR with polarization and adhesion.
      In vivo adhesion was also increased by anti-VEGF. HBO treatment of IR
      significantly increased the VEGF protein in both gracilis and pulmonary
      vasculature. Alpha-2-antiplasmin significantly reversed the HBO-induced increase
      of VEGF in gracilis muscle. CONCLUSIONS: These results suggest that HBO inhibits
      CD18 polarization and neutrophil adhesion in IR injury through a VEGF-mediated
      pathway involving the extracellular matrix plasminogen system.

PMID- 29062665
TI  - Spontaneous Regression of Lymphangiomas in a Single Center Over 34 Years.
AB  - BACKGROUND: A lymphangioma, also called a lymphatic malformation, is a congenital
      condition that frequently occurs in young children. It is classified into 3
      groups depending on the size of the cysts (macrocystic, microcystic, and mixed).
      Spontaneous regression occurs in some cases; however, the characteristics of
      patients who show regression have not been studied previously. Furthermore, the
      types and the timing of the initial treatment are still controversial. Therefore,
      we statistically analyzed the occurrence of short-term spontaneous regression,
      patient age at original occurrence, cyst types, cyst sizes, and cyst locations in
      patients diagnosed with peripheral localized lymphangiomas in a single children
      center over 34 years. METHODS: We retrospectively collected the data of 153
      patients and reviewed the medical charts. RESULTS: Spontaneous regression
      occurred only in macrocystic or mixed type; regression was most frequent in
      patients who, at the time of onset, were more than 2 years old. CONCLUSIONS: We
      concluded that elderly patients with macrocystic or mixed type lymphangioma may
      have to wait for treatment for over 3 months from the initial onset. Conversely,
      microcystic type could not be expected to show regression in a short period, and
      prompt initiation of the treatments may be required. The difference of the
      regression or not may depend on the characteristics of the lymph flow.

PMID- 29062666
TI  - New Internal Fixation Technique for Transconjunctival Fat Repositioning.
AB  - To treat tear trough deformities in young patients, transconjunctival orbital fat
      repositioning has been widely used. Although internal fixation of transposed fat
      enables more secure and stable fixation than the externalized percutaneous suture
      method, the latter is used more commonly because of the narrow operation field
      and consequent technical difficulty of the internal fixation method. We describe
      a novel technique using a newly devised needle (Chang's needle) that facilitates
      internal fixation of transposed fat pedicles.

PMID- 29062667
TI  - Hair Transplantation in Migraine Headache Patients.
AB  - BACKGROUND: Migraine headache is a primary neurologic disease affecting millions
      of people worldwide. As a consequence, quality of life is diminished,
      productivity suffers (through loss of work force), and treatment costs are
      substantial. The occurrence rate in the general population is quite high, with
      women accounting for 3 of every 4 cases. METHODS: Between January 2011 and May
      2012, a total of 221 patients received hair transplants. Another 590 patients
      underwent hair transplantation between June 2012 and December 2016. Initially
      (first interval), patients were not questioned on migraine headaches in
      preoperative visits, but questioning was regularly done thereafter. Overall, 150
      patients given transplants in the first period were surveyed by phone regarding
      preoperative migraine headaches. Aside from the 1 incidental discovery, no other
      instances of migraine emerged. Headache origins were occipital-frontal in 2
      patients, occipital-temporal in 2 patients, and occipital-temporal-frontal in the
      2 others. Donor/receiver areas in hair transplantation and migraine trigger zones
      shared locations. Headache frequencies ranged from 4 to 8 days per month
      (average, 6 days), and pain scores were 5-8 (10 being highest). Duration of pain
      was 3-5 hours (average, 4 hours). All six patients had used various medications,
      such as triptans, ergot, and nonsteroidal anti-inflammatory drugs, before hair
      transplantation. The 1 female patient was a 32-year-old seeking treatment for
      alopecia, with a 6-year history of migraine headaches. The male patients
      presenting with androgenetic alopecia (grade 4-5 by Norwood classification) had 6
      to 20-year migrainous histories. RESULTS: After hair transplantation, each
      migraine sufferer was checked once in the first month and then once every 3
      months. Those who could not appear in person after the first year were evaluated
      by phone every 3 months. Migraine headaches had ceased in all 6 patients, none of
      whom used medical treatments for migraines thereafter. The postoperative
      improvement each patient experienced was dramatic (P < 0.001). Overall, the mean
      intensity of headaches declined from 6.6 +/- 1.47 to 0, on an analog scale of 1
      10 (P < 0.001); and mean headache frequency was reduced from 5.83 +/- 1.03/month
      to 0/month (P < 0.001). Likewise, the migraine pain index fell from a mean of
      149.33 +/- 19.21/month to mean of 0/month (P < 0.001). CONCLUSIONS: This report
      details 6 patients who experienced abatement of migraine headache symptoms
      following hair transplantation. The positive effects of hair transplantation on
      migraine headache and potential mechanisms of action are also discussed.

PMID- 29062668
TI  - A Novel Funnel-Shaped Flap for Reconstruction Surgery after Total
      Laryngopharyngectomy with Total Glossectomy.
AB  - Reconstruction following total laryngopharyngectomy with total glossectomy
      (TLPTG) is challenging. To reconstruct this extended range of mucosal defect, it
      is necessary to overcome the remarkable discrepancy of apertures of oral and
      esophageal sides. We report a case of reconstruction surgery for total
      laryngopharyngectomy with total glossectomy with a funnel-shaped rectus abdominis
      musclocutaneous flap. The patient recovered without major complications and could
      keep a relatively good swallowing function. We believe this simple method should
      contribute to cases with complicated ablation.

PMID- 29062669
TI  - Reconstruction of Near-Total Loss of the Upper and Lower Lips due to Purpura
      Fulminans with Local Tissue and a Dual-Skin Paddled Anterolateral Thigh Flap.
AB  - It is difficult to totally reconstruct the lip, achieving good functional and
      aesthetic results. There have been few reports of reconstructing complete lip
      defects. Moreover, upper and lower lip necrosis by purpura fulminans has not been
      reported. We present a case of a 60-year-old male purpura fulminans patient with
      upper and lower lip necrosis. Fortunately, our patient had retained his oral
      commissure function. We reconstructed this defect with an orbicularis oris muscle
      skin-mucosal pedicled flap derived from the region between the nasolabial folds
      for upper lip; a similar bipedicled flap for the lower lip and the donor site was
      closed with a dual-skin paddled anterolateral thigh flap. Postoperative results
      were satisfactory, that is, no lip tightness or aperture restriction was seen,
      and symmetry had been achieved. The new lips exhibited complete sensory recovery.
      Drooling was minimal during rest and feeding. We could select a method that
      combined the advantages of local and free flaps. We consider our method for this
      defect is superior to those described in previous studies, in that the
      restoration of lip sensation and oral sphincter function can be achieved to some
      extent in 1 stage while preserving the oral commissure function.

PMID- 29062670
TI  - Comment-Box Modification to Muscle-Sparing Latissimus Dorsi Design for
      Microvascular Anastomosis Coverage.

PMID- 29062671
TI  - Enabling Remote Monitoring Using Free Apps and Smart Devices for a Free-Flap
      Adjunct Monitor.
AB  - Remote monitoring capability does not currently exist for Periflux (Perimed AB,
      Jarfalla, Sweden) laser Doppler and other perfusion monitors. Two simple
      adaptations using free apps (applications) and smart devices can enable
      transmission of the perfusion readout to the surgeon's smartphone. A literature
      review was conducted to identify reports relating to remote free flap monitoring.
      In addition, 2 wireless methodologies are devised: One method uses a free app
      that converts a smart device into a camera, stationed next to the perfusion
      monitor, to stream live video of the laser Doppler readout to the surgeon's
      smartphone; a second method uses a free app installed on a bedside laptop
      computer, which is connected to the laser Doppler flowmeter via a data cord. A
      live feed of the computer's desktop as a teleconference host is transmitted to
      the surgeon's smart device over the Internet. These 2 methodologies were employed
      on 9 and 8 free flaps, respectively, as a pilot study. All free flaps were
      monitored remotely for 4-6 days with near 100% reliability. The Internet
      connectivity became disrupted only on several occasions, requiring simple Wi-Fi
      and software reset. Minor mechanical issues were encountered with the video
      streaming method. Literature review identified very few articles describing
      remote monitoring of free flaps. The 2 methodologies reported here provided
      reliable continuous transmission of quantitative data of flap perfusion to smart
      devices via Internet connection, which can revolutionize the microsurgeon's
      practice if his/her adjunctive perfusion monitor with display does not yet have
      Wi-Fi capability.

PMID- 29062672
TI  - Successful Second Microsurgical Replantation for Amputated Penis.
AB  - Penile amputation is a rare emergency, but the best method for its repair is
      required due to the organ's functional and societal role. Since the first
      successful microsurgical replantation of the amputated penis, microsurgical
      techniques have matured and become the standard treatment for the penile
      replantation. However, the successful second microsurgical replantation for
      amputated penis has been rarely reported. We present the case of a 40-year-old
      man with schizophrenia who had a past history of penile self-mutilation and
      successful replantation at another hospital 2 years ago. After stopping oral
      medication for schizophrenia, he again cut his penis with a kitchen knife. We
      successfully replanted the amputated penis by anastomosing both circumflex
      arteries, the superficial dorsal vein, and the deep dorsal vein using
      microsurgical techniques. Postoperatively, the foreskin of the replanted penis
      gradually developed partial necrosis, requiring surgical debridement. The
      aesthetic and functional results were satisfactory and retrograde urethrography
      showed no evidence of leakage and stricture of the urethra. Although skin
      necrosis after penile replantation has been reported as an unavoidable process
      owing to the nature of injury, the rate would be higher after secondary
      replantation because of scar formation due to the previous operation. Therefore,
      our case of successful secondary replantation suggests that skin necrosis would
      be a predictable postoperative complication and the debridement timing of the
      devitalized foreskin should be closely monitored, and also secondary amputation
      is not a contraindication of replantation.

PMID- 29062673
TI  - Tocopherol levels in different mango varieties correlate with MiHPPD expression
      and its over-expression elevates tocopherols in transgenic Arabidopsis and
      tomato.
AB  - Mango fruit tocopherol levels vary in different varieties during ripening. This
      study shows that tocopherol accumulation is highly correlated with its p
      hydroxyphenyl pyruvate dioxygenase (MiHPPD) gene expression during ripening.
      MiHPPD transcript is ethylene induced and differentially expressed in four mango
      varieties used in this study. Higher/lower accumulation of tocopherol (mainly
      alpha-tocopherol) was achieved by heterologous expression of MiHPPD in
      Arabidopsis and tomato. The results suggest that tocopherol accumulation in mango
      fruit is correlated to MiHPPD gene expression. Over-expression of MiHPPD gene
      channelizes the flux towards tocophreol biosynthesis and could be used as a
      potential tool for metabolic engineering.

PMID- 29062674
TI  - Molecular docking and simulation studies of Phyllanthus amarus phytocompounds
      against structural and nucleocapsid proteins of white spot syndrome virus.
AB  - White spot disease caused by white spot syndrome virus (WSSV) is a lethal disease
      for shrimp. Envelope structural proteins play a major role in viral attachment
      and are believed to be the initial molecules to interact with the host cell.
      Thus, the envelope proteins have been preferred as a potential molecular target
      for drug discovery. In the present investigation, molecular docking and
      simulation analysis were performed to predict the binding efficiency of
      phytocompounds identified from Phyllanthus amarus with major envelope proteins,
      VP26, VP28, and VP110, and a nucleocapsid protein VP664 of WSSV. The docking
      result reveals that the compounds 2H-1-benzopyran-6-ol, 3,4-dihydro-2,5,7,8
      tetramethyl-2-(4,8,12-trimethyltridecyl)-acetate and 1,4-benzenediamine, N,N'
      diphenyl exhibited highest binding energy with the envelope proteins. The
      mobility of protein-ligand binding complex at various time intervals was
      validated by molecular dynamics and simulation study. Therefore, P. amarus
      phytocompounds were found to be most suitable inhibitors for the antiviral
      treatment for WSSV infection.

PMID- 29062675
TI  - MicroRNA-like RNAs in plant pathogenic fungus Fusarium oxysporum f. sp. niveum
      are involved in toxin gene expression fine tuning.
AB  - MicroRNA-like RNAs (milRNAs) are short non-coding regulatory sRNAs which play an
      important role in regulating gene expression at the post-transcriptional level by
      targeting mRNAs for degradation or inhibiting protein translation. To explore the
      presence of milRNAs in Fusarium oxysporum f. sp. niveum (Fon) and analyze their
      expression at different propagules, two categories of sRNAs were identified from
      Fon hyphae and microconidia using illumina sequencing. A total of 650,960 and
      561,114 unique sRNAs were obtained from the hyphae and microconidia samples. With
      a previously constructed pipeline to search for microRNAs, 74 and 56 milRNA
      candidates were identified in hyphae and microconidia, respectively, based on the
      short hairpin structure analysis. Global expression analysis showed an
      extensively differential expression of sRNAs between the two propagules.
      Altogether, 78 significantly differently expressed milRNAs were identified in two
      libraries. Target prediction revealed two interesting genes involved in
      trichothecene production, necrosis and ethylene-inducing peptide 1 (NEP1)
      biosynthesis and in silico analysis indicated that they were down-regulated by
      Fon-miR7696a-3p and Fon-miR6108a. The expression levels of these two milRNAs were
      further validated by qRT-PCR and the results were consistent. The negative
      correlation of the expression levels between these two milRNAs and their
      potential target genes imply that they play a role in trichothecene and NEP1
      biosynthesis. And this negative regulation for toxin-related gene expression is
      more specific in microconidia. The present study provides the first large-scale
      characterization of milRNAs in Fon and the comparison between hyphae and
      microconidia propagules gives an insight into how milRNAs are involve in toxin
      biosynthesis.

PMID- 29062676
TI  - Effect of growth conditions on beta-glucosidase production using Flourensia
      cernua leaves in a solid-state fungal bioprocess.
AB  - Flourensia cernua foliage was used in a solid-state fungal bioprocess to identify
      factors that could affect beta-glucosidase production such as growth medium
      components and partial identification of molecules from the plant material. Under
      an exploratory experimental design, each variable had their distinctive result on
      conditions, which affects and could further improve beta-glucosidase production.
      Under the experimental design, 1482 U/L of beta-glucosidase were detected, which
      marks an improvement in production compared to levels obtained in a control
      treatment with an activity of 1092 U/L. It was shown that inoculum, water content
      and pH were the factors with the greater effect on beta-glucosidase production.
      Polyphenolic content and cellulosic fiber in the form of raw fiber were measured
      to assess compound degradation of the plant material. Although fiber content was
      apparently unaffected, polyphenolic content decreased; beta-glucosidase was
      produced by A. niger GH1. This behavior could be associated with fiber level and
      polyphenolic content because molecules of this type can be hydrolyzed by beta
      glucosidase. According to our results, F. cernua biomass can be used as a carbon
      source for beta-glucosidase production in a short culture time.

PMID- 29062677
TI  - Assessment of hazelnut husk as a lignocellulosic feedstock for the production of
      fermentable sugars and lignocellulolytic enzymes.
AB  - The present work focuses firstly on the evaluation of the effect of laccase on
      enzymatic hydrolysis of hazelnut husk which is one of the most abundant
      lignocellulosic agricultural residues generated in Turkey. In this respect, the
      co-enzymatic treatment of hazelnut husk by cellulase and laccase, without a
      conventional pretreatment step is evaluated. Using 2.75 FPU/g substrate (40 g/L
      substrate) and a ratio of 131 laccase U/FPU achieved the highest reducing sugars
      concentration. Gas chromatography mass spectrometry confirmed that the
      hydrolysate was composed of glucose, xylose, mannose, arabinose and galactose.
      The inclusion of laccase in the enzyme mixture [carboxymethyl cellulase (CMCase)
      and beta-glucosidase] increased the final glucose content of the reducing sugars
      from 20 to 50%. Therefore, a very significant increase in glucose content of the
      final reducing sugars concentration was obtained by laccase addition.
      Furthermore, the production of cellulases and laccase by Pycnoporus sanguineus
      DSM 3024 using hazelnut husk as substrate was also investigated. Among the
      hazelnut husk concentrations tested (1.5, 6, 12, 18 g/L), the highest CMCase
      concentration was obtained using 12 g/L husk concentration on the 10th day of
      fermentation. Besides CMCase, P. sanguineus DSM 3024 produced beta-glucosidase
      and laccase using hazelnut husk as carbon source. In addition to CMCase and beta
      glucosidase, the highest laccase activity measured was 2240 +/- 98 U/L (8.89 +/-
      0.39 U/mg). To the best of our knowledge, this is the first study to report
      hazelnut husk hydrolysis in the absence of pretreatment procedures.

PMID- 29062678
TI  - Genome sequence of Talaromyces piceus 9-3 provides insights into lignocellulose
      degradation.
AB  - Many species of Penicillium have exhibited great potential for lignocellulose
      hydrolysis. The filamentous fungus Talaromyces piceus 9-3 (anamorph: Penicillium
      piceum), which was isolated from compost wastes in China, was sequenced in this
      study. Compared with the cellulase producer T. reesei, T. piceus 9-3 processes a
      lignocellulolytic enzyme system comprising more diverse enzymatic components,
      especially hemicellulases. This report will facilitate the use of this strain for
      biomass degradation.

PMID- 29062680
TI  - Comparison of subjective and objective measures of office workers' sedentary
      time.
AB  - Sedentary behavior is an independent and prominent risk factor for chronic
      disease. Occupational sitting is likely to be the largest determinant of overall
      daily sitting time. Gathering accurate data on sedentary behaviors is essential
      to determine prevalence and effectiveness of interventions to reduce sedentary
      time. The purpose of this research was to determine whether self-reported
      sedentary time assessed by the Paffenbarger Physical Activity Questionnaire
      (PPAQ) and the Occupational Sitting and Physical Activity Questionnaire (OSPAQ)
      was related to objectively assessed sedentary time by the activPAL3 activity
      monitor. In the spring of 2015, 44 women employed full-time at Slippery Rock
      University participated in this study. Participants were predominantly Caucasian
      (95%), middle-aged (48 +/- 10 years), and had an average BMI of 30.5 +/- 8.2. A
      positive, weak correlation was found in sedentary time between the PPAQ (14.65 +/
      2.77 h) and the activPAL3 (17.71 +/- 1.46 h) over a 24 hour day (r = 0.253; p =
      0.098; n = 44). Thirty-nine of the 44 participants significantly underestimated
      their sedentary time as compared to the activPAL3 (3.06 +/- 2.76 h; p = 0.001). A
      positive, weak correlation was also found in sedentary time between the OSPAQ
      (5.96 +/- 1.11 h) and the activPAL3 (5.69 +/- 1.06 h) during the 8.5 hour work
      day (r = 0.100; p = 0.518; n = 44). Future studies examining sedentary behaviors
      should use caution when only considering the use of subjective recall surveys.
      This is especially true when self-reported behaviors are used to inform health
      promotion programs and create universal recommendations aimed to reduce sedentary
      time.

PMID- 29062679
TI  - Cross-Cultural Effects of Cannabis Use Disorder: Evidence to Support a Cultural
      Neuroscience Approach.
AB  - PURPOSE OF REVIEW: Cannabis use disorders (CUDs) are prevalent worldwide. Current
      epidemiological studies underscore differences in behaviors that contribute to
      cannabis use across cultures that can be leveraged towards prevention and
      treatment of CUDs. This review proposes a framework for understanding the effects
      of cross-cultural differences on psychological, neural, and genomic processes
      underlying CUDs that has the potential to inform global policies and impact
      global public health. RECENT FINDINGS: We found that cultural factors may
      influence (1) the willingness to acknowledge CUD-related symptoms among
      populations of different countries, and (2) neural responses related to the sense
      of self, perception, emotion, and attention. These findings leverage the
      potential effects of culture on neural mechanisms underlying CUDs. SUMMARY: As
      the number of individuals seeking treatment for CUDs increases globally, it is
      imperative to incorporate cultural considerations to better understand and serve
      differing populations and develop more targeted treatment strategies and
      interventions.

PMID- 29062681
TI  - Factors associated with the human papillomavirus (HPV) vaccination across three
      countries following vaccination introduction.
AB  - Direct international comparisons which aim to understand how factors associated
      with human papillomavirus (HPV) vaccine initiation and attitudes towards the HPV
      vaccination in parents differ are scarce. Parents (n = 179) of daughters aged 9
      17 years in the US, UK and Australia completed an online survey in 2011 with
      questions measuring daughters' HPV vaccination status, HPV knowledge, HPV
      vaccination knowledge, and statements assessing attitude towards the HPV vaccine.
      The strongest factor associated with vaccination status across all countries was
      parental HPV knowledge (p < 0.001). Parents with both very low and very high
      knowledge scores were less likely to have vaccinated their daughters. Parents
      with higher HPV vaccination knowledge scores intended to vaccinate their
      daughters (if not already vaccinated) for protective reasons (p < 0.001), while
      those whose daughters were already vaccinated understood that vaccination
      protection was not 100% and that their daughters may still be at risk of getting
      HPV (p < 0.05). Compared to the UK and Australia, a higher proportion of parents
      with unvaccinated daughters from the US were worried about the side-effects of
      the HPV vaccination (US: 60.5%, UK: 36.4%, AUS: 15.4%; p < 0.05), believed that
      getting the vaccination might be a hassle (US: 21.1%, UK: 0%, AUS: 7.7%; p <
      0.05), and that the vaccine was too new (US: 44.7%, UK: 22.7%, AUS: 7.7%; p <
      0.05). This study adds to the understanding of how parents may influence
      vaccination uptake by demonstrating the effect of knowledge and the parental
      attitudes towards HPV vaccination across three countries.

PMID- 29062682
TI  - Transudative chylothorax in a patient with lymphangioleiomyomatosis.
AB  - Transudative chylothorax is a rare type of pleural effusion. It has been
      described to be present in the setting of liver cirrhosis, heart failure,
      amyloidosis, nephrotic syndrome, superior vena cava thrombosis, sclerosing
      mesenteritis and heart failure. We present the case of an 86-year-old woman with
      a right-side transudative chylothorax associated with heart failure and
      lymphangioleiomyomatosis.

PMID- 29062683
TI  - Zoster-like cutaneous metastatic adenocarcinoma of the lung: A case report.
AB  - The zosteriform pattern is an infrequent cutaneous finding in oncologic patients
      who have a skin metastasis from a different primary source. Herein we report a
      case of adenocarcinoma of the lung which presented with zoster-like lesions along
      the thoracic dermatome. The histopathology indicated a metastatic neoplasm with
      variable glandular formations. Immunohistochemistry results pointed to the
      diagnosis of metastasized lung cancer. We suggest physicians should consider this
      rare diagnosis when experiencing similar cases.

PMID- 29062684
TI  - PaCER - A fully automated method for electrode trajectory and contact
      reconstruction in deep brain stimulation.
AB  - Deep brain stimulation (DBS) is a neurosurgical intervention where electrodes are
      permanently implanted into the brain in order to modulate pathologic neural
      activity. The post-operative reconstruction of the DBS electrodes is important
      for an efficient stimulation parameter tuning. A major limitation of existing
      approaches for electrode reconstruction from post-operative imaging that prevents
      the clinical routine use is that they are manual or semi-automatic, and thus both
      time-consuming and subjective. Moreover, the existing methods rely on a
      simplified model of a straight line electrode trajectory, rather than the more
      realistic curved trajectory. The main contribution of this paper is that for the
      first time we present a highly accurate and fully automated method for electrode
      reconstruction that considers curved trajectories. The robustness of our proposed
      method is demonstrated using a multi-center clinical dataset consisting of N = 44
      electrodes. In all cases the electrode trajectories were successfully identified
      and reconstructed. In addition, the accuracy is demonstrated quantitatively using
      a high-accuracy phantom with known ground truth. In the phantom experiment, the
      method could detect individual electrode contacts with high accuracy and the
      trajectory reconstruction reached an error level below 100 MUm (0.046 +/- 0.025
      mm). An implementation of the method is made publicly available such that it can
      directly be used by researchers or clinicians. This constitutes an important step
      towards future integration of lead reconstruction into standard clinical care.

PMID- 29062685
TI  - Loss of inhibition in sensorimotor networks in focal hand dystonia.
AB  - OBJECTIVE: To investigate GABA-ergic receptor density and associated brain
      functional and grey matter changes in focal hand dystonia (FHD). METHODS: 18
      patients with FHD of the right hand and 18 age and gender matched healthy
      volunteers (HV) participated in this study. We measured the density of GABA-A
      receptors using [11C] Flumazenil and perfusion using [15O] H2O. Anatomical images
      were also used to measure grey matter volume with voxel-based morphometry (VBM).
      RESULTS: In FHD patients compared to HV, the vermis VI of the right cerebellum
      and the left sensorimotor cortex had a decrease of Flumazenil binding potential
      (FMZ-BP), whereas the striatum and the lateral cerebellum did not show
      significant change. Bilateral inferior prefrontal cortex had increased FMZ-BP and
      an increase of perfusion, which correlated negatively with disease duration. Only
      the left sensorimotor cortex showed a decrease of grey matter volume.
      INTERPRETATION: Impairments of GABAergic neurotransmission in the cerebellum and
      the sensorimotor cortical areas could explain different aspects of loss of
      inhibitory control in FHD, the former being involved in maladaptive plasticity,
      the latter in surround inhibition. Reorganization of the inferior prefrontal
      cortices, part of the associative network, might be compensatory for the loss of
      inhibitory control in sensorimotor circuits. These findings suggest that
      cerebellar and cerebral GABAergic abnormalities could play a role in the
      functional imbalance of striato-cerebello-cortical loops in dystonia.

PMID- 29062687
TI  - Integrity of the corpus callosum in patients with periventricular nodular
      heterotopia related epilepsy by FLNA mutation.
AB  - OBJECTIVE: To investigate the quantitative diffusion properties of the corpus
      callosum (CC) in a large group of patients with periventricular nodular
      heterotopia (PNH) related epilepsy and to further investigate the effect of
      Filamin A (FLNA) mutation on these properties. METHODS: Patients with PNH (n =
      34), subdivided into FLNA-mutated (n = 11) and FLNA-nonmutated patients (n = 23)
      and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion
      imaging scan (64 direction). Fractional anisotropy (FA) and mean diffusivity (MD)
      were measured in the three major subdivisions of the CC (genu, body and
      splenium). Correlations between DTI metric changes and clinical parameters were
      also evaluated. Furthermore, the effect of FLNA mutation on structural integrity
      of the corpus callosum was examined. RESULTS: Patients with PNH and epilepsy had
      significant reductions in FA for the genu and splenium of the CC, accompanied by
      increases in MD for the splenium, as compared to healthy controls. There were no
      correlations between clinical parameters of epilepsy and MD. The FA value in the
      splenium negatively correlated with epilepsy duration. Interestingly, FLNA
      mutated patients showed significantly decreased FA for all three major
      subdivisions of the CC, and increased MD for the genu and splenium, as compared
      to HCs and FLNA-nonmutated patients. CONCLUSIONS: These findings support the
      conclusion that patients with epilepsy secondary to PNH present widespread
      microstructural changes found in the corpus callosum that extend beyond the
      macroscopic MRI-visible lesions. This study also indicates that FLNA may affect
      white matter integrity in this disorder.

PMID- 29062686
TI  - Differential associations of metabolic risk factors on cortical thickness in
      metabolic syndrome.
AB  - OBJECTIVE: Metabolic syndrome (MetS) refers to a cluster of risk factors for
      cardiovascular disease, including obesity, hypertension, dyslipidemia, and
      hyperglycemia. While sizable prior literature has examined associations between
      individual risk factors and quantitative measures of cortical thickness (CT),
      only very limited research has investigated such measures in MetS. Furthermore,
      the relative contributions of these risk factors to MetS-related effects on brain
      morphology have not yet been studied. The primary goal of this investigation was
      to examine how MetS may affect CT. A secondary goal was to explore the relative
      contributions of individual risk factors to regional alterations in CT, with the
      potential to identify risk factor combinations that may underlie structural
      changes. METHODS: Eighteen participants with MetS (mean age = 59.78 years) were
      age-matched with 18 healthy control participants (mean age = 60.50 years). CT
      measures were generated from T1-weighted images and groups were contrasted using
      whole-brain general linear modeling. A follow-up multivariate partial least
      squares correlation (PLS) analysis, including the full study sample with complete
      risk factor measurements (N = 53), was employed to examine which risk factors
      account for variance in group structural differences. RESULTS: Participants with
      MetS demonstrated significantly reduced CT in left hemisphere inferior parietal,
      rostral middle frontal, and lateral occipital clusters and in a right hemisphere
      precentral cluster. The PLS analysis revealed that waist circumference, high
      density lipoprotein cholesterol (HDL-C), triglycerides, and glucose were
      significant contributors to reduced CT in these clusters. In contrast, diastolic
      blood pressure showed a significantly positive association with CT while systolic
      blood pressure did not emerge as a significant contributor. Age was not
      associated with CT. CONCLUSION: These results indicate that MetS can be
      associated with regionally specific reductions in CT. Importantly, a novel link
      between a risk factor profile comprising indices of obesity, hyperglycemia,
      dyslipidemia and diastolic BP and localized alterations in CT emerged. While the
      pathophysiological mechanisms underlying these associations remain incompletely
      understood, these findings may be relevant for future investigations of MetS and
      might have implications for treatment approaches that focus on specific risk
      factor profiles with the aim to reduce negative consequences on the structural
      integrity of the brain.

PMID- 29062688
TI  - Changes in subcortical resting-state functional connectivity in patients with
      psychophysiological insomnia after cognitive-behavioral therapy: Changes in
      resting-state FC after CBT for insomnia patients.
AB  - STUDY OBJECTIVES: To examine the resting-state functional connectivity (FC)
      between subcortical regions in relation to whole-brain activity in patients with
      psychophysiological insomnia (PI) and changes following cognitive-behavioral
      therapy for insomnia (CBTi). METHODS: The FC between subcortical seed regions
      (caudate, putamen, pallidum, amygdala, thalamus, and hippocampus) and whole-brain
      voxels were compared between the PI group (n = 13, mean age: 51.0 +/- 10.2 years)
      and good sleepers (GS, n = 18, mean age: 42.7 +/- 12.3 years). Also, in the PI
      group, FC was compared before and after 5 weeks of CBTi. RESULTS: Compared to the
      GS group, the PI group exhibited stronger FC between the thalamus and prefrontal
      cortex and between the pallidum and precuneus but weaker FC between the pallidum
      and angular gyrus, the caudate and orbitofrontal cortex, and the hippocampus and
      fusiform gyrus. After CBTi, the PI group exhibited decreased FC between the
      thalamus and parietal cortex, the putamen and motor cortices, and the amygdala
      and lingual gyrus, but increased FC between the caudate and supramarginal gyrus,
      the pallidum and orbitofrontal cortex, and the hippocampus and frontal/parietal
      gyri. CONCLUSIONS: The present findings demonstrate different FC in PI patients
      compared to GS and provide insight into the neurobiological rationale for CBTi.

PMID- 29062689
TI  - Occipital dysembryoplastic neuroepithelial tumor presenting as adult-onset
      temporal epilepsy.
AB  - Dysembryoplastic neuroepithelial tumor (DNET) is a benign brain tumor which
      commonly presents as childhood-onset temporal lobe epilepsy (TLE). We present a
      case of histologically proven DNET with a clinical presentation and scalp EEG
      suggestive of adult-onset TLE. MRI showed an occipital lesion. PET showed
      abnormal metabolism of the occipital lesion and the ipsilateral temporal lobe;
      raising concern for an abnormal functional network reorganization. Intracranial
      EEG showed interictal spikes and seizures originating from the occipital lesion
      with no seizures emanating from the temporal lobe. Occipital DNET due to their
      chronic nature can reorganize the network and mimic TLE.

PMID- 29062690
TI  - Paroxysmal dysphasia in a 68 year-old man: Enhancing the MRI spectrum!
AB  - Brain tumor-related epilepsy is a common complication of primary and metastatic
      brain tumors with seizures often representing the first manifestation of the
      tumor. The size and location of the tumor can make detection of epileptiform
      discharges on scalp electroencephalogram and safe surgical resection challenging.
      We describe a case of a patient with glioblastoma multiforme presenting as
      dominant temporal lobe epilepsy. Seizures were manifest as episodes of speech
      arrest on a background of long-standing history of episodic speech difficulty and
      headache. In this case, recognizing a change in semiology allowed diagnosis of a
      high-grade glioma. Use of electrocorticography during surgical excision of the
      tumor guided safe maximal excision without damage to eloquent cortex and helped
      confirm the diagnosis of brain tumor-related epilepsy.

PMID- 29062691
TI  - New onset refractory status epilepticus due to primary angiitis of the central
      nervous system.
AB  - Primary Angiitis of the central nervous system is a rare and poorly understood
      variant of vasculitis. We narrate a case of a 46-year-old male who presented with
      new onset refractory status epilepticus mimicking autoimmune encephalitis. In
      this case we are reporting clues that could be useful for diagnosis and extensive
      literature review on the topic.

PMID- 29062692
TI  - Efficacy of perampanel in a patient with epilepsia partialis continua.
AB  - Perampanel is the first-in-class selective and noncompetitive alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. It is authorized
      in the U.S. and Europe as an add-on antiepileptic drug for partial-onset
      seizures, and for primary generalized tonic-clonic seizures. Single reports have
      also indicated a potential efficacy for myoclonic jerks. Here, we report a
      patient whose drug-resistant epilepsia partialis continua completely resolved
      after adding perampanel. She has remained seizure-free in an eighteen-month
      follow-up period. Epilepsia partialis continua reemerged transiently after
      perampanel was temporarily discontinued, with no recurrence after its
      reintroduction. Therefore, this effect was reproducible, and suggests that it
      might be worth trying perampanel in similar settings.

PMID- 29062693
TI  - Computational deciphering of biotic stress associated genes in tomato (Solanum
      lycopersicum).
AB  - Tomato (Solanum lycopersicum) is one of the major vegetable plant and a model
      system for fruit development. Its global importance is due to its lycopene
      pigment which has anti-oxidative and anti-cancerous properties. Though > 1.5 M
      biotic stress associated ESTs of tomato are available but cumulative analysis to
      predict genes is warranted. Availability of whole genome de novo assembly can
      advantageously be used to map them over different chromosome. Further, available
      0.14 M catalogued markers can be used to introgress specific desirable genes in
      varietal improvement program. We report here 57 novel genes associated with
      biotic stress of tomato along with 50 genes having physical location over
      different chromosomes. We also report 52 cis-regulating elements and 69 putative
      miRNAs which are involved in regulation of these biotic stresses associated
      genes. These putative candidate genes associated with biotic stress can be used
      in molecular breeding in the endeavor of tomato productivity along with its
      sustainable germplasm management.

PMID- 29062694
TI  - Use of a cerebral protection device for the laser extraction of a pacemaker lead
      traversing a patent foramen ovale.

PMID- 29062696
TI  - Atrial fibrillation ablation with persistent left superior vena cava detected
      during intracardiac echocardiography.

PMID- 29062695
TI  - Inaccurate diagnosis of Brugada syndrome in a healthy woman based on SCN5A
      mutation classification.

PMID- 29062697
TI  - Novel gene mutation identified in a patient with arrhythmogenic ventricular
      cardiomyopathy.

PMID- 29062698
TI  - T-wave oversensing during left ventricular pacing causing inappropriate
      defibrillation.

PMID- 29062699
TI  - Unilateral sympathetic ganglion denervation in the management of sustained
      ventricular tachycardia.

PMID- 29062700
TI  - Oral quinine sulfate for the treatment of electrical storm and prevention of
      recurrent shocks in Brugada syndrome after failed cilostazol therapy.

PMID- 29062701
TI  - Changing place, changing future: Repositioning a subcutaneous implantable
      cardioverter-defibrillator can resolve inappropriate shocks secondary to
      myopotential oversensing.

PMID- 29062702
TI  - High-density mapping of the slow pathway in a patient with atrioventricular nodal
      reentry given intranasal Etripamil during the NODE-1 study.

PMID- 29062704
TI  - Coronary sinus ostium in the lateral right atrium: Implications for the
      electrophysiologist.

PMID- 29062703
TI  - Esophageal T-tube: A novel approach to atrioesophageal fistula repair.

PMID- 29062705
TI  - Transvenous nonfluoroscopic pacemaker implantation during pregnancy guided by 3
      dimensional electroanatomic mapping.

PMID- 29062706
TI  - Extreme "cannon A waves" and pulsatile skin color in complete heart block.

PMID- 29062707
TI  - The "absent" left atrial appendage....

PMID- 29062708
TI  - Acute right coronary artery occlusion after radiofrequency catheter ablation of
      cavotricuspid isthmus: Vascular response assessed by optical frequency domain
      imaging.

PMID- 29062709
TI  - Encapsulated pleural effusion due to Haemophilus influenzae biotype II in a child
      with trisomy 21: A case report and literature review.
AB  - Haemophilus influenzae (Hi) can colonize in the upper respiratory tract and cause
      severe pulmonary infections, especially among immunocompromised children. Herein,
      we report a case of left encapsulated pleural effusion (EPE) due to Hi in a 24
      month-old girl with trisomy 21. She was already vaccinated against Hi type b. The
      Hi biotype II was isolated from both the blood and aspirated sputum obtained upon
      admission. Ampicillin/sulbactam 180 mg/kg/day was administered intravenously for
      34 days with oxygen supplementation for 4 days. She clinically recovered without
      undergoing thoracic drainage. One month after discharge, the girl developed acute
      otitis media, and the throat swab was cultured. Nontypeable Hi with the same
      biotype II was isolated, and the infection was controlled by administering
      antimicrobials. In this report, a literature review regarding the EPE due to Hi
      in children is also summarized. Pediatric clinicians should be aware of the
      possibility of Hi-related EPE because of its rapid progression, although it is
      rare in clinical settings. In addition, they need to consider the possibility of
      repetitive respiratory infections with Hi in a child with trisomy 21.

PMID- 29062710
TI  - Brucellosis: A cause of meningitis not to neglect.
AB  - Brucellosis is the most frequent bacteria zoonosis in the world, with more than
      half a million new cases each year [1]. It is also the most significant zoonos in
      the edge of the Mediterranean Sea [2]. This zoonosis is capable of affecting
      humans and cause polymorphic clinical manifestations. In Morocco, the southern
      regions are the main affected areas [3]. We are reporting the observation of a 17
      year-old male patient, who presented a febrile meningeal syndrome for 9 months
      without sensitivo-motor deficit. Tuberculosis is frequently evoked in such
      clinical presentations because Morocco is an endemic country, brucellosis is
      therefore often forgotten. The results of lumbar puncture, magnetic resonance
      imaging (MRI) and especially serology aided to conclude to a neuro-brucellosis.
      The outcome was favourable with antibiotic therapy.

PMID- 29062712
TI  - Weight loss induced by quetiapine in a 22q11.2DS patient.

PMID- 29062711
TI  - Strongyloides Hyperinfection Syndrome causing fatal meningitis and septicemia by
      Citrobacter koseri.
AB  - Citrobacter koseri is a gram-negative bacillius that belongs to the
      Enterobacteriaceae family. It is an uncommon pathogen that typically causes
      meningitis and brain abscesses in children, however central nervous system (CNS)
      infections are rarely found in adults. We present a case of C. koseri meningitis
      in an immunocompetent adult secondary to intestinal micro-perforation caused by
      Strongyloides A 76-year-old man admitted for asthma exacerbation developed septic
      shock. A lumbar puncture revealed bacterial meningitis. Blood and CSF cultures
      grew Citrobacter koseri with identical susceptibilities, suggesting infection by
      one strain. Despite broad-spectrum antibiotics, the patient expired of multi
      organ failure. Autopsy identified diffuse alveolar hemorrhage as the immedi ate
      cause of death with a heavy burden of Strongyloides stercoralis in his
      gastrointestinal system, lungs, and meninges. Citrobacter koseri is a gram
      negative bacillus of the Enterobacteriaceae family. It is an uncommon pathogen
      that typically causes meningitis and brain abscesses in children. Infections in
      adults occur in immunocompromised hosts or instances where an insult creates a
      port of entry. This is the first documented case of C.koseri sepsis in an
      immunocompetent host associated with Strongyloides Hyperinfection Syndrome (SHS),
      where massive parasitic intestinal invasion reaches pulmonary circulation and
      perforates the alveolar membrane. This case highlights that presence of rare
      enterobacterial infections should prompt consideration of differentials including
      SHS.

PMID- 29062713
TI  - Treating mitochondrial disorders requires full exploitation of available
      therapeutic options.

PMID- 29062715
TI  - Testis cancer incidentally found following delayed presentation of traumatic
      testicular rupture.

PMID- 29062714
TI  - A successful case of salvage kidney transplantation using the recipient gonadal
      vein to bypass a major outflow obstruction.

PMID- 29062716
TI  - Clear cell tubopapillary renal cell carcinoma mimicking polycystic kidney
      disease: A case report.
AB  - Clear cell tubopapillary renal cell carcinoma (CCTP-RCC) is a distinct histologic
      subtype of RCC recognized for its unique clinicopathologic and
      immunohistochemical features. A 72-year-old man with presumed polycystic kidney
      disease (PKD) and bilateral clear cell RCC (CC-RCC) underwent left radical
      nephrectomy and right partial nephrectomy 20 years ago at an outside hospital. On
      surveillance imaging, RCC recurrence was suspected and right radical nephrectomy
      was performed. Histologic and gross examination of the right remaining kidney was
      consistent with CCTP-RCC. Review of his original pathology report revealed both
      kidneys in fact represented CCTP-RCC, mimicking PKD.

PMID- 29062717
TI  - Multiple exo-glycosidases in human serum as detected with the substrate DNP-alpha
      GalNAc. I. A new assay for lysosomal alpha-N-acetylgalactosaminidase.
AB  - This paper presents a new assay to determine the activity of the lysosomal enzyme
      alpha-N-acetylgalactosaminidase (Naga, EC 3.2.1.49) in human serum. It is based
      on the use of a new chromogenic substrate, DNP-alpha-GalNAc (2,4-dinitrophenyl-N
      acetyl-alpha-D-galactosaminide) and is performed at pH 4.3 and 37  degrees C.
      This allows continuous monitoring of the absorbance of the released DNP. The
      assay can be performed with a standard spectrophotometer. Compared to established
      methods using an endpoint assay with MU-alpha-GalNAc (4-methylumbelliferyl
      GalNAc), the present method gives a ca. 3-fold higher specific activity, while
      only one tenth of the serum concentration in the assay is required. Hence, the
      assay is at least 30-fold more sensitive than that with MU-alpha-GalNAc. The pH
      dependence of the reaction with DNP-alpha-GalNAc in the pH 3.5 to 6.5 region,
      while using 4% serum in the assay, shows only one peak around pH 4. This pH
      optimum is similar to that reported with MU-alpha-GalNAc. In the accompanying
      paper (Albracht and Van Pelt (2017) Multiple exo-glycosidases in human serum as
      detected with the substrate DNP-alpha-GalNAc. II. Three alpha-N
      acetylgalactosaminidase-like activities in the pH 5 to 8 region. Biochim.
      Biophys. Acta 159 (2017) Part I and II), the method is used to show that, under
      special assay conditions, three more Naga-like activities can be uncovered in
      human serum.

PMID- 29062718
TI  - Multiple exo-glycosidases in human serum as detected with the substrate DNP-alpha
      GalNAc. II. Three alpha-N-acetylgalactosaminidase-like activities in the pH 5 to
      8 region.
AB  - With the substrate DNP-alpha-GalNAc (2,4-dinitrophenyl-N-acetyl-alpha-d
      galactosaminide) three alpha-N-acetylgalactosaminidase-like activities could be
      distinguished in serum, in addition to the classical lysosomal enzyme (Naga, EC
      3.2.1.49, pH optimum at 4). Two activities had optima in the pH 5 to 6 region and
      one peaked around pH 8. Like the Naga activity at pH 4, the activity at pH 8 was
      detectable under standard assay conditions. However, the two activities in the pH
      5 to 6 range were not readily apparent in such assays. They could be unmasked as
      separate activities only when low serum concentrations were used. Addition of 1%
      saturated ammonium sulphate to the assay medium stimulated these activities. All
      activities in the pH 5 to 8 range decreased with increasing serum concentration
      in the assay, suggesting the presence of endogenous inhibitors. The activities
      between pH 5 and 6 might be similar to an activity described in 1996, which was
      considerably elevated in serum of patients with great variety of cancers (N.
      Yamamoto, V.R. Naraparaju, and S.O. Asbell (1996). Deglycosylation of serum
      vitamin D3-binding protein leads to immunosuppression in cancer patients. Cancer
      Res. 56, 2827-2811).

PMID- 29062719
TI  - A highly sensitive liquid chromatography electrospray ionization mass
      spectrometry method for quantification of TMA, TMAO and creatinine in mouse
      urine.
AB  - Our method describes the quantification in mouse urine of trimethylamine (TMA),
      trimethylamine N-oxide (TMAO) and creatinine. The method combines derivatization
      of TMA, with ethyl bromoacetate, and LC chromatographic separation on an ACE C18
      column. The effluent was continuously electrosprayed into the linear ion trap
      mass spectrometer (LTQ), which operated in selective ion monitoring (SIM) modes
      set for targeted analytes and their internal standards (IS). All validation
      parameters were within acceptable ranges of analytical method validation
      guidelines. Intra- and inter-day assay precision and accuracy coefficients of
      variation were <3.1%, and recoveries for TMA and TMAO were 97-104%. The method
      developed uses a two-step procedure. Firstly, TMA and TMAO are analyzed without a
      purification step using a 5-min gradient cap-LC- SIMs analysis, then creatinine
      is analyzed using the same experimental conditions. The method is robust, highly
      sensitive, reproducible and has the high-throughput capability of detecting TMA,
      TMAO and creatinine at on-column concentrations as low as 28 pg/mL, 115 pg/mL and
      1 ng/mL, respectively. The method is suitable for analysis of TMA, TMAO and
      creatinine in both male and female mouse urine. The key benefits of the method
      are: *The small sample volume of urine required, which overcomes the difficulties
      of collecting sufficient volumes of urine at defined times.*No sample pre
      treatment is necessary.*The quantification of TMA, TMAO and creatinine using the
      same cap-LC-MS method.

PMID- 29062720
TI  - A method exploiting direct communication between phasor measurement units for
      power system wide-area protection and control algorithms.
AB  - Synchrophasor measurements from Phasor Measurement Units (PMUs) are the primary
      sensors used to deploy Wide-Area Monitoring, Protection and Control (WAMPAC)
      systems. PMUs stream out synchrophasor measurements through the IEEE C37.118.2
      protocol using TCP/IP or UDP/IP. The proposed method establishes a direct
      communication between two PMUs, thus eliminating the requirement of an
      intermediate phasor data concentrator, data mediator and/or protocol parser and
      thereby ensuring minimum communication latency without considering communication
      link delays. This method allows utilizing synchrophasor measurements internally
      in a PMU to deploy custom protection and control algorithms. These algorithms are
      deployed using protection logic equations which are supported by all the PMU
      vendors. Moreover, this method reduces overall equipment cost as the algorithms
      execute internally in a PMU and therefore does not require any additional
      controller for their deployment. The proposed method can be utilized for fast
      prototyping of wide-area measurements based protection and control applications.
      The proposed method is tested by coupling commercial PMUs as Hardware-in-the-Loop
      (HIL) with Opal-RT's eMEGAsim Real-Time Simulator (RTS). As illustrative example,
      anti-islanding protection application is deployed using proposed method and its
      performance is assessed. The essential points in the method are: *Bypassing
      intermediate phasor data concentrator or protocol parsers as the synchrophasors
      are communicated directly between the PMUs (minimizes communication delays).*Wide
      Area Protection and Control Algorithm is deployed using logic equations in the
      client PMU, therefore eliminating the requirement for an external hardware
      controller (cost curtailment)*Effortless means to exploit PMU measurements in an
      environment familiar to protection engineers.

PMID- 29062721
TI  - Peroxidase production and ligninolytic potentials of fresh water bacteria
      Raoultella ornithinolytica and Ensifer adhaerens.
AB  - Interest in novel ligninolytic bacteria has remained topical due to, in part, the
      maneuverability of the bacterial genome. Conversely, the fungal genome lacks the
      dexterity for similar maneuverability thus, posing challenges in the fungal
      enzyme yield optimization process. Some impact of this situation includes the
      inability to commercialize the bio-catalytic process of lignin degradation by
      fungi. Consequently, this study assessed some fresh water bacteria isolates for
      ligninolytic and peroxidase properties through the utilization and degradation of
      model lignin compounds (guaiacol and veratryl alcohol) and the decolourization of
      selected ligninolytic indicator dyes; Azure B (AZB), Remazol Brilliant Blue R
      (RBBR) and Congo Red (CR). Bacterial strains with appreciable ligninolytic and
      peroxidase production potentials were identified through 16S rDNA sequence
      analysis and the nucleotide sequences deposited in the GenBank. About 5 isolates
      were positive for the degradation of both guaiacol (GA) and veratryl alcohol (VA)
      thus, accounting for about 17% of the test isolates. Similarly, AZB, RBBR and CR
      were respectively decolorized by 3, 2 and 5 bacterial strains thus, accounting
      for 10%, 7% and 17% of the test isolates. Two of the test bacterial strains were
      able to decolourize AZB, RBBR and CR respectively and these bacterial strains
      were identified as Raoultella ornithinolytica OKOH-1 and Ensifer adhaerens NWODO
      2 with respective accession numbers as KX640917 and KX640918. Upon quantitation
      of the peroxidase activities; 5250 +/- 0.00 U/L was recorded against Raoultella
      ornithinolytica OKOH-1 and 5833 +/- 0.00 U/L against Ensifer adhaerens NWODO-2.
      The ligninolytic and dye decolourization properties of Raoultella ornithinolytica
      OKOH-1 and Ensifer adhaerens NWODO-2 marks for novelty particularly, as dyes with
      arene substituents were decolourized. Consequently, the potentials for the
      industrial applicability of these test bacterial strains abound as there is a
      dearth of information on organisms with such potentials.

PMID- 29062722
TI  - Draft genome sequence of Sclerospora graminicola, the pearl millet downy mildew
      pathogen.
AB  - Sclerospora graminicola pathogen is the most important biotic production
      constraints of pearl millet in India, Africa and other parts of the world. We
      report a de novo whole genome assembly and analysis of pathotype 1, one of the
      most virulent pathotypes of S. graminicola from India. The draft genome assembly
      contained 299,901,251 bp with 65,404 genes. This study may help understand the
      evolutionary pattern of pathogen and aid elucidation of effector evolution for
      devising effective durable resistance breeding strategies in pearl millet.

PMID- 29062723
TI  - Review and comparison of quality standards, guidelines and regulations for
      laboratories.
AB  - BACKGROUND: The variety and number of laboratory quality standards, guidelines
      and regulations (hereafter: quality documents) makes it difficult to choose the
      most suitable one for establishing and maintaining a laboratory quality
      management system. OBJECTIVES: There is a need to compare the characteristics,
      suitability and applicability of quality documents in view of the increasing
      efforts to introduce quality management in laboratories, especially in clinical
      diagnostic laboratories in low income and middle income countries. This may
      provide valuable insights for policy makers developing national laboratory
      policies, and for laboratory managers and quality officers in choosing the most
      appropriate quality document for upgrading their laboratories. METHOD: We
      reviewed the history of quality document development and then selected a subset
      based on their current use. We analysed these documents following a framework for
      comparison of quality documents that was adapted from the Clinical Laboratory
      Standards Institute guideline GP26 Quality management system model for clinical
      laboratory services. RESULTS: Differences were identified between national and
      international, and non-clinical and clinical quality documents. The most salient
      findings were the absence of provisions on occurrence management and customer
      service in almost all non-clinical quality documents, a low number of safety
      requirements aimed at protecting laboratory personnel in international quality
      documents and no requirements regarding ethical behaviour in almost all quality
      documents. CONCLUSION: Each laboratory needs to investigate whether national
      regulatory standards are present. These are preferred as they most closely suit
      the needs of laboratories in the country. A laboratory should always use both a
      standard and a guideline: a standard sums up the requirements to a quality
      management system, a guideline describes how quality management can be integrated
      in the laboratory processes.

PMID- 29062724
TI  - Identifying HIV infection in South African women: How does a fourth generation
      HIV rapid test perform?
AB  - BACKGROUND: HIV rapid tests (RT) play an important role in tackling the HIV
      pandemic in South Africa. Third generation RT that detect HIV antibodies are
      currently used to diagnose HIV infection at the point of care. Determine Combo
      (DC) is the first fourth generation RT that detects both p24 antigen (p24Ag) and
      HIV antibodies (Ab), theoretically reducing the window period and increasing
      detection rates. Early detection of maternal HIV infection is important to
      mitigate the high risk of vertical transmission associated with acute maternal
      infection. OBJECTIVES: We assessed the performance of the DC RT against third
      generation RT in antenatal and post-partum women. METHODS: Third generation RT
      Advance Quality and Acon were used in a serial algorithm to diagnose HIV
      infection in antenatal and post-partum women over six months at a tertiary
      hospital in Johannesburg, South Africa. This data provided the reference against
      which the DC RT was compared on plasma and whole blood samples. RESULTS: The 1019
      participants comprised 345 (34%) antenatal and 674 (66%) post-partum women.
      Ninety women (8.8%) tested HIV-positive of whom 59 (66%) were tested antenatally,
      and 31 (34%) post-partum yielding prevalence rates of 17.1% and 4.6%
      respectively. The sensitivity and specificity of the Ab component of DC on plasma
      antenatally was 100% (93.8% - 100%) and 100% (98.6% - 100%) respectively and post
      partum was 100% (88.9% - 100%) and 99.6% (98.8% - 99.9%) respectively. One false
      positive and not a single true positive p24Ag was detected. Of 505 post-partum
      women who tested HIV-negative 6-12 months prior to enrolment, 12 (2.4%)
      seroconverted. CONCLUSION: The fourth generation DC offered no advantage over
      current third generation RT in the diagnosis of HIV infection.

PMID- 29062725
TI  - Immunohaematological reference values for HIV-negative healthy adults in
      Botswana.
AB  - BACKGROUND: Clinical laboratories in Botswana have relied entirely on the
      reference intervals for normal immunohaematological values provided by
      manufacturers' kits and textbooks. OBJECTIVES: The aim of this study was to
      determine the means, medians, 2.5th and 97.5th percentile reference intervals,
      for normal immunohaematological values in healthy adults in Botswana. METHOD: A
      total of 261 healthy participants comprising 126 men (48%) and 135 (52%) women
      were enrolled in the southern part of Botswana, and immunological and
      haematological laboratory parameters were measured. RESULTS: The mean age was
      28.8 (95% Confidence Interval [CI] 27.7-29.8) years, with a median of 27 years
      and a range 18-66 years. The mean haemoglobin level was significantly lower for
      women (12.4 g/dL; 95% CI 12.1% - 12.7%) than men (15.1 g/dL; 95% CI 14.9% -
      15.3%). The women's haemoglobin reference values (9.0 g/dL - 15.0 g/dL) levels
      were lower than observed in predominantly White populations (12.0 g/dL - 16.0
      g/dL), but comparable with regional consensus reference intervals (9.5 g/dL -
      15.8 g/dL) recently defined for East and Southern Africa. CONCLUSION: The
      established values provide an important tool for patient management and could
      influence decisions on inclusion of participants and adverse events in clinical
      trials conducted locally.

PMID- 29062726
TI  - Impact of mentorship on WHO-AFRO Strengthening Laboratory Quality Improvement
      Process Towards Accreditation (SLIPTA).
AB  - BACKGROUND: The improvment of the quality of testing services in public
      laboratories is a high priority in many countries. Consequently, initiatives to
      train laboratory staff on quality management are being implemented, for example,
      the World Health Organization Regional Headquarters for Africa (WHO-AFRO)
      Strengthening Laboratory Management Towards Accreditation (SLMTA). Mentorship may
      be an effective way to augment these efforts. METHODS: Mentorship was implemented
      at four hospital laboratories in Lesotho, three districts and one central
      laboratory, between June 2009 and December 2010. The mentorship model that was
      implemented had the mentor fully embedded within the operations of each of the
      laboratories. It was delivered in a series of two mentoring engagements of six
      and four week initial and follow-up visits respectively. In total, each
      laboratory received 10 weeks mentorship that was separated by 6-8 weeks. Quality
      improvements were measured at baseline and at intervals during the mentorship
      using the WHO-AFRO Strengthening Laboratory Quality Improvement Process Towards
      Accreditation (SLIPTA) checklist and scoring system. RESULTS: At the beginning of
      the mentorship, all laboratories were at the SLIPTA zero star rating. After the
      initial six weeks of mentorship, two of the three district laboratories had
      improved from zero to one (out of five) star although the difference between
      their baseline (107.7) and the end of the six weeks (136.3) average scores was
      not statistically significant (p = 0.25). After 10 weeks of mentorship there was
      a significant improvement in average scores (182.3; p = 0.034) with one
      laboratory achieving WHO-AFRO three out of a possible five star status and the
      two remaining laboratories achieving a two star status. At Queen Elizabeth II (QE
      II) Central Laboratory, the average baseline score was 44%, measured using a
      section-specific checklist. There was a significant improvement by five weeks
      (57.2%; p = 0.021). CONCLUSION: The mentorship programme in this study resulted
      in significant measurable improvements towards preparation for the WHO-AFRO
      SLIPTA process in less than six months. We recommend that mentorship be
      incorporated into laboratory quality improvement and management training
      programmes such as SLMTA, in order to accelerate the progress of laboratories
      towards achieving accreditation.

PMID- 29062727
TI  - Systematic reviews of diagnostic test accuracy for evidence-based diagnostic
      practice in Africa.

PMID- 29062728
TI  - Laboratory testing improves diagnosis and treatment outcomes in primary health
      care facilities.
AB  - OBJECTIVE: To determine if use of basic laboratory tests improves diagnosis and
      treatment outcomes in outpatients attending rural primary health care facilities.
      SETTING: Six rural health centres in Kenya. DESIGN: Cross-sectional study to
      observe change in diagnosis and treatment made by clinical officers after
      laboratory testing in outpatients attending six rural health centres in Kenya.
      SUBJECT: The diagnosis and treatment of 1134 patients attending outpatient
      services in six rural health centres were compared before and after basic
      laboratory testing. Essential clinical diagnostic equipment and laboratory tests
      were established at each health centre. Clinical officers and laboratory
      technicians received on-site refresher training in good diagnostic practices and
      laboratory procedures before the study began. RESULTS: Laboratory tests were
      ordered on 704 (62.1%) patients. Diagnosis and treatment were changed in 45% of
      tested patients who returned with laboratory results (21% of all patients
      attending the clinics). 166 (23.5%) patients did not return to the clinician for
      a final diagnosis and management decision after laboratory testing. Blood slide
      examination for malaria parasites, wet preparations, urine microscopy and stool
      microscopy resulted in most changes to diagnosis. There was no significant change
      in drug costs after laboratory testing. The greatest changes in numbers of
      recorded diseases following laboratory testing was for intestinal worms (53%) and
      malaria (21%). CONCLUSION: Effective use of basic laboratory tests at primary
      health care level significantly improves diagnosis and patient treatment. Use of
      laboratory testing can be readily incorporated into routine clinical practice. On
      site refresher training is an effective means of improving the quality of patient
      care and communication between clinical and laboratory staff.

PMID- 29062729
TI  - Strengthening Laboratory Management Towards Accreditation: The Lesotho
      experience.
AB  - INTRODUCTION: The Lesotho Ministry of Health and Social Welfare's (MOHSW) 5-year
      strategic plan, as well as their national laboratory policy and yearly
      operational plans, directly addresses issues of accreditation, indicating their
      commitment to fulfilling their mandate. As such, the MOHSW adopted the World
      Health Organization Regional Headquarters for Africa's Stepwise Laboratory
      Quality Improvement Toward Accreditation (WHO-AFRO-SLIPTA) process and
      subsequently rolled out the Strengthening Laboratory Management Towards
      Accreditation (SLMTA) programme across the whole country, becoming the first
      African country to do so. METHODS: SLMTA in Lesotho was implemented in two
      cohorts. Twelve and nineteen laboratory supervisors and quality officers were
      enrolled in Cohort 1 and Cohort 2, respectively. These 31 participants
      represented 18 of the 19 laboratories nationwide. For the purposes of this
      programme, the Queen Elizabeth II (QE II) Central Laboratory had its seven
      sections of haematology, blood bank, cytology, blood transfusion, microbiology,
      tuberculosis laboratory and chemistry assessed as separate sections. Performance
      was tracked using the WHO-AFRO-SLIPTA checklist, with assessments carried out at
      baseline and at the end of SLMTA. Two methods were used to implement SLMTA: the
      traditional 'three workshops' approach and twinning SLMTA with mentorship. The
      latter, with intensive follow-up visits, was concluded in 9 months and the former
      in 11 months. A standard data collection tool was used for site visits. RESULTS:
      Of the 31 participants across both cohorts, 25 (81%) graduated (9 from Cohort 1
      and 16 from Cohort 2). At baseline, all but one laboratory attained a rating of
      zero stars, with the exception attaining one star. At the final assessment, 7 of
      the 25 laboratories examined at baseline were still at a rating of zero stars,
      whilst 8 attained one star, 5 attained two stars and 4 attained three stars. None
      scored above three stars. The highest percentage improvement for any laboratory
      was 51%, whereas the least improved dropped by 6% when compared to its baseline
      assessment. The most improved areas were corrective actions (34%) and documents
      and records (32%). Process improvement demonstrated the least improvement (10%).
      CONCLUSION: The SLMTA programme had an immediate, measurable and positive impact
      on laboratories in Lesotho. This success was possible because of the leadership
      and ownership of the programme by the MOHSW, as well as the coordination of
      partner support.

PMID- 29062730
TI  - Distribution and association of hs-CRP with cardiovascular risk variables of
      metabolic syndrome in adolescent learners.
AB  - OBJECTIVE: Metabolic syndrome (MetS) and its associated cardiovascular risk are
      on the increase in children. High-sensitivity C-reactive protein (hs-CRP) has
      emerged as a useful marker for inflammation associated with atherosclerosis and
      cardiovascular disease. Our aim was to determine the distribution of hs-CRP in an
      effort to identify the MetS variable that is critical in modulating plasma CRP
      levels in a population of South African adolescents. DESIGN: A cross-sectional
      analytical study design was used for this investigation, where the dependent and
      independent variables were measured simultaneously. METHODS: Anthropometric
      variables, blood pressure, fasting blood glucose and lipids were performed on 324
      consenting learners aged 15-18 years from three different ethnic groups (Black,
      White and Coloured). The National Cholesterol Education Program Adult Treatment
      Panel III (NCEP ATP III) for ages 15-18 year olds was used to define MetS.
      RESULTS: The prevalence of MetS and obesity was 3.7% and 7.1%, respectively. The
      hs-CRP levels were significantly higher in subjects with a waist-circumference
      greater than the 90th percentile (p < 0.01) and in obese learners with MetS, but
      was lower in adolescents with normal weight and MetS. Median hs-CRP levels
      increased with an increasing number of metabolic abnormalities and exceeded 3
      mg/L in 19% of adolescents. Gender and ethnic differences were observed.
      CONCLUSION: Our findings suggest that obesity and waist circumference appear to
      be major mediators of hs-CRP levels in South African adolescents.

PMID- 29062731
TI  - Global health: Integrating national laboratory health systems and services in
      resource-limited settings.
AB  - Laboratory systems worldwide are challenged not only by the need to compete for
      scarce resources with other sections of national health care programmes, but also
      with the lack of understanding of the critical role that laboratories play in the
      accurate diagnosis and monitoring of patients suffering from high-burdens of
      disease. An effective approach to establishing cost-effective laboratory systems
      that provide rapid and accurate test results for optimal impact on patient care
      is to move away from disease-specific programmes and establish integrated
      laboratory services. An integrated laboratory network provides all primary
      diagnostic services needed for care and treatment without requiring patients to
      go to different laboratory facilities for specific tests. Such a network focuses
      on providing quality-assured basic laboratory testing through the use of common
      specimen collection, reporting and diagnostic platforms that can be used across
      diseases. An integrated laboratory system also provides specimen transport to
      specialised laboratories and an environment conducive to the introduction and use
      of new and more complex technologies that would benefit the patient population
      and public health systems as a whole. As such, this article described various
      strategies for, and practical examples of, the successful integration of
      laboratory services.

PMID- 29062732
TI  - Optimising automation of a manual enzyme-linked immunosorbent assay.
AB  - OBJECTIVE: Enzyme-linked immunosorbent assays (ELISAs) are widely used to
      quantify immunoglobulin levels induced by infection or vaccination. Compared to
      conventional manual assays, automated ELISA systems offer more accurate and
      reproducible results, faster turnaround times and cost effectiveness due to the
      use of multianalyte reagents. DESIGN: The VaccZymeTM Human Anti-Haemophilus
      influenzae type B (Hib) kit (MK016) from The Binding Site Company was optimised
      to be used on an automated BioRad PhDTM system in the Immunology Laboratory
      (National Health Laboratory Service) in Tygerberg, South Africa. METHODS: An
      automated ELISA system that uses individual well incubation was compared to a
      manual method that uses whole-plate incubation. RESULTS: Results were calculated
      from calibration curves constructed with each assay. Marked differences in
      calibration curves were observed for the two methods. The automated method
      produced lower-than-recommended optical density values and resulted in invalid
      calibration curves and diagnostic results. A comparison of the individual steps
      of the two methods showed a difference of 10 minutes per incubation cycle. All
      incubation steps of the automated method were subsequently increased from 30
      minutes to 40 minutes. Several comparative assays were performed according to the
      amended protocol and all calibration curves obtained were valid. Calibrators and
      controls were also included as samples in different positions and orders on the
      plate and all results were valid. CONCLUSION: Proper validation is vital before
      converting manual ELISA assays to automated or semi-automated methods.

PMID- 29062733
TI  - Prolonged febrile illness due to CTX-M-15 extended-spectrum beta-lactamase
      producing Klebsiella pneumoniae infection in Nigeria.
AB  - We report on an 8-year-old patient with septicaemia unresponsive to therapy for
      five weeks. Undetected, extended-spectrum beta-lactamase (ESBL) production by the
      infecting Klebsiella strain was regarded as responsible for treatment failure.
      Intravenously administered imipenem during the sixth week led to sustained
      resolution of fever. Resource-limited hospitals can incur prohibitive costs from
      ESBL-producer infections because of diagnostic limitations and consequent
      treatment failure involving prolonged supportive therapy.

PMID- 29062734
TI  - Experience of quality management system in a clinical laboratory in Nigeria.
AB  - ISSUES: Quality-management systems (QMS) are uncommon in clinical laboratories in
      Nigeria, and until recently, none of the nation's 5 349 clinical laboratories
      have been able to attain the certifications necessary to begin the process of
      attaining international accreditation. Nigeria's Human Virology Laboratory (HVL),
      however, began implementation of a QMS in 2006, and in 2008 it was determined
      that the laboratory conformed to the requirements of ISO 9001:2000 (now 2008),
      making it the first diagnostic laboratory to be certified in Nigeria. The HVL has
      now applied for the World Health Organization (WHO) accreditation preparedness
      scheme. The experience of the QMS implementation process and the lessons learned
      therein are shared here. DESCRIPTION: In 2005, two personnel from the HVL spent
      time studying quality systems in a certified clinical laboratory in Dakar,
      Senegal. Following this peer-to-peer technical assistance, several training
      sessions were undertaken by HVL staff, a baseline assessment was conducted, and
      processes were established. The HVL has monitored its quality indicators and
      conducted internal and external audits; these analyses (from 2007 to 2009) are
      presented herein. LESSONS LEARNED: Although there was improvement in the pre
      analytical and analytical indicators analysed and although data-entry errors
      decreased in the post-analytical process, the delay in returning laboratory test
      results increased significantly. There were several factors identified as causes
      for this delay and all of these have now been addressed except for an identified
      need for automation of some high-volume assays (currently being negotiated).
      Internal and external audits showed a trend of increasing non-conformities which
      could be the result of personnel simply becoming lax over time. Application for
      laboratory accreditation, however, could provide the renewed vigour needed to
      correct these non-conformities. RECOMMENDATION: This experience shows that
      sustainability of the QMS at present is a cause for concern. However, the tiered
      system of accreditation being developed by WHO-Afro may act as a driving force to
      preserve the spirit of continual improvement.

PMID- 29062735
TI  - The World Health Organization African region external quality assessment scheme
      for anti-HIV serology.
AB  - A regional external quality assessment scheme (REQAS) for anti-HIV serology aimed
      to objectively assess reliability and quality of HIV testing processes in the
      African region. This involved the distribution of proficiency testing (PT) panels
      to participating laboratories from 2002 to 2010. During the survey period, this
      included 16 distributions of PT panels to 49 laboratories in 30 countries, and
      the overall average score during the nine-year survey period was 98.9%, with a
      frequency of accurate detection, of anti-HIV-1 and/or anti-HIV-2 antibodies in
      the PT panels, ranging from 93% to 100%. Problems highlighted included lack of
      human resources and frequent stock outs of test kits, reagents and consumables
      for routine HIV testing. The design of the REQAS allowed appraisal of the
      reliability of anti-HIV serological testing methods utilised by laboratories for
      clinical assessment of patients and/or surveillance programmes. The REQAS was
      able to demonstrate that laboratories participating in the REQAS performed well
      and sustained their participation in the scheme. This bodes well for clinical
      diagnosis, surveillance and training activities at these reference laboratories.

PMID- 29062736
TI  - The African Journal of Laboratory Medicine - Advancing Laboratory Medicine and
      Science in Africa.

PMID- 29062737
TI  - Guest Editor Introduction.

PMID- 29062738
TI  - Long term outcomes of transcatheter aortic valve implantation (TAVI): a
      systematic review of 5-year survival and beyond.
AB  - BACKGROUND: Transcatheter aortic valve implantation/replacement (TAVI/TAVR) is
      becoming more frequently used to treat aortic stenosis (AS), with increasing push
      for the procedure in lower risk patients. Numerous randomized controlled trials
      have demonstrated that TAVI offers a suitable alternative to the current gold
      standard of surgical aortic valve replacement (SAVR) in terms of short-term
      outcomes. The present review evaluates long-term outcomes following TAVI
      procedures. METHODS: Literature search using three electronic databases was
      performed up to June 2017. Studies which included 20 or more patients undergoing
      TAVI procedures, either as a stand-alone or concomitant procedure and with a
      follow-up of at least 5 years, were included in the present review. Literature
      search and data extraction were performed by two independent researchers.
      Digitized survival data were extracted from Kaplan-Meier curves in order to re
      create the original patient data using an iterative algorithm and subsequently
      aggregated for analysis. RESULTS: Thirty-one studies were included in the present
      analysis, with a total of 13,857 patients. Two studies were national registries,
      eight were multi-institutional collaborations and the remainder were
      institutional series. Overall, 45.7% of patients were male, with mean age of
      81.5+/-7.0 years. Where reported, the mean Logistic EuroSCORE (LES) was 22.1+/
      13.7 and the mean Society of Thoracic Surgeons (STS) score was 9.2+/-6.6. The
      pooled analysis found 30-day mortality, cerebrovascular accidents, acute kidney
      injury (AKI) and requirement for permanent pacemaker (PPM) implantation to be
      8.4%, 2.8%, 14.4%, and 13.4%, respectively. Aggregated survival at 1-, 2-, 3-, 5-
      and 7-year were 83%, 75%, 65%, 48% and 28%, respectively. CONCLUSIONS: The
      present systematic review identified acceptable long-term survival results for
      TAVI procedures in an elderly population. Extended follow-up is required to
      assess long-term outcomes following TAVI, particularly before its application is
      extended into wider population groups.

PMID- 29062739
TI  - Pros and cons of transcatheter aortic valve implantation (TAVI).
AB  - Transcatheter aortic valve implantation (TAVI) or replacement (TAVR) was recently
      approved by the FDA for intermediate risk patients with severe aortic stenosis
      (AS). This technique was already worldwide adopted for inoperable and high-risk
      patients. Improved device technology, imaging analysis and operator expertise has
      reduced the initial worrisome higher complications rate associated with TAVR,
      making it comparable to surgical aortic valve replacement (SAVR). However, many
      answers need to be addressed before adoption in lower risk patients. This paper
      highlights the pros and cons of TAVI based mostly on randomized clinical trials
      involving the two device platforms approved in the United States. We focused our
      analysis on metrics that will play a key role in expanding TAVR indication in
      healthier individuals. We review the significance and gave a perspective on
      paravalvular leak (PVL), valve performance, valve durability, leaflet thrombosis,
      stroke and pacemaker requirement.

PMID- 29062740
TI  - Outcomes of surgical and transcatheter aortic valve replacement in the
      octogenarians-surgery still the gold standard?
AB  - BACKGROUND: Contemporary options for aortic valve replacement (AVR) include
      transcatheter and surgical approaches (TAVR and SAVR). As evidence accrues for
      TAVR in high and intermediate risk patients, some clinicians advocate that all
      patients aged over 80 years should only receive TAVR. Our aim was to investigate
      the utility of SAVR and minimally invasive AVR (mAVR) among octogenarians in the
      current era of TAVR. METHODS: From 2002 to 2015, 1,028 octogenarians underwent
      isolated AVR; 306 TAVR and 722 SAVR, of which 378 patients underwent mAVR.
      Logistic regression and Cox modeling were used to evaluate overall operative
      mortality and mid-term survival, respectively. Patients were stratified based on
      procedural approaches (mAVR or full sternotomy for SAVR, and transfemoral or
      alternate access for TAVR). Median follow-up was 35 [interquartile range (IQR) 14
      65] months. RESULTS: Compared to SAVR patients, TAVR patients were relatively
      older (86.2 versus 84.2 years) with co-morbidities such as chronic kidney disease
      (CKD), diabetes mellitus (DM), cerebrovascular disease (CVD), and prior
      myocardial infarction (MI), all P<0.05. The mean STS-PROM for the TAVR group was
      statistically higher, 6.81 versus 5.58 for the SAVR group (P<0.001). The median
      in-hospital LOS was statistically higher for the SAVR group (P<0.05). Cox
      proportional hazard modeling, adjusted for temporal differences in procedure and
      patient selection, identified age, New York Heart Association (NYHA) class
      III/IV, preoperative creatinine, severe chronic lung disease, prior cardiac
      surgery as significant predictors of decreased survival (all P<0.05), while type
      of intervention (approach) was non-contributory. Adjusted operative mortality
      stratified by procedure approaches was similar between full sternotomy SAVR and
      mAVR, and between alternative access and transfemoral TAVR. CONCLUSIONS: After
      adjusting for confounders, TAVR (regardless of approach), SAVR, and mAVR had
      comparable operative mortality and mid-term survival. Treatment decisions should
      be individualized with consensus from a multi-disciplinary heart team, taking
      into account patient co morbidities, frailty, and quality of life. We believe
      certain patient groups will still benefit from SAVR even in this elderly
      population.

PMID- 29062741
TI  - Clinical outcomes and prognostic factors of transcatheter aortic valve
      implantation in bicuspid aortic valve patients.
AB  - BACKGROUND: The purpose of this study was to evaluate the outcomes of
      transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic
      valve stenosis (AS). METHODS: From April 2012 and December 2016, 108 patients
      with bicuspid AS underwent TAVR using the Sapien XT (34 patients) and Sapien 3
      (74 patients) valves. Procedural and clinical outcomes were assessed according to
      VARC-2 criteria and compared between the two devices. RESULTS: In the overall
      cohort, the majority of patients were male (71.3%) with an intermediate surgical
      risk and a mean Society of Thoracic Surgeons (STS) score of 5.2%. Compared to the
      Sapien XT group, the Sapien 3 group had a significantly lower STS score (3.3%+/
      2.0% vs. 6.7%+/-3.6%; P=0.001). Compared to the Sapien XT group, the Sapien 3
      group had a significantly lower rate of moderate or severe paravalvular leak
      (2.7% vs. 14.7%; P=0.03) and higher device success (97.3% vs. 82.4%; P=0.006).
      There were no significant differences between the two groups in terms of 30-day
      all-cause mortality, stroke, life-threatening bleeding, major vascular
      complication and acute kidney injury (stage 2 or 3). Cumulative all-cause
      mortality at 1-year follow-up was 6.9%. There were no significant differences in
      cumulative event rates for all-cause mortality at 1-year follow-up between the
      two groups (9.4% vs. 4.6%; log-rank P=0.47). By univariate analysis, major
      vascular complication was significantly associated with overall all-cause
      mortality [hazard ratios (HR): 7.57; 95% confidence interval (CI): 1.51-37.86;
      P=0.014]. CONCLUSIONS: TAVR using the balloon-expandable valves provided
      acceptable procedural and clinical outcomes in patients with bicuspid AS. The new
      generation Sapien 3 valves showed improved procedural outcomes compared to the
      early-generation Sapien XT valves.

PMID- 29062742
TI  - Long-term outcomes and prosthesis performance after transcatheter aortic valve
      replacement: results of self-expandable and balloon-expandable transcatheter
      heart valves.
AB  - BACKGROUND: Data on transcatheter aortic valve replacement (TAVR) long-term
      clinical outcomes and hemodynamic performance of the self-expandable CoreValve
      (CV) and the balloon-expandable Edwards SAPIEN XT (ES) (Edwards Lifesciences,
      Irvine, California, USA) transcatheter heart valves (THV) are limited. Therefore,
      this study aimed to compare long-term clinical outcome data and hemodynamic
      performance of TAVR with either CV or ES. METHODS: We reviewed prospectively
      collected data of 171 patients treated with TAVR for severe aortic stenosis (AS)
      at our center between June 2007 and December 2010, with last follow-up contact in
      2016. RESULTS: Out of 171 patients treated with TAVR at our Institution, 87
      received a CV and 84 an ES THV. Mean age was 81 [78-85] years, and mean Society
      of Thoracic Surgeons (STS) score was 7.5% (4.5-13.9%). Hemodynamic success by
      Valve Academic Research Consortium (VARC) definition was 97.1%. Mean trans
      prosthetic gradient remained low and stable during follow-up in both groups (at 5
      year 9.2+/-6.4 versus 12.7+/-5.1 mmHg, P=0.10). Late prosthesis failure occurred
      in 4 cases (2.4%). Thirty-day mortality was 4.7%, and estimated survival rates by
      Kaplan-Meyer after 1, 5 and 8 years were 87.6%, 44.9%, and 24.5%, respectively,
      without difference between THV groups. Rates of cardiovascular death, stroke,
      myocardial infarction (MI) and congestive heart failure (CHF) were also similar
      with CV and ES at long-term follow-up. History of CHF, pre-existent severe mitral
      regurgitation, paravalvular leak grade >=2+, and chronic obstructive pulmonary
      disease were independent predictors of late mortality at multivariable analysis.
      CONCLUSIONS: Clinical and hemodynamic outcomes of patients treated by self
      expandable CV or balloon-expandable ES THV were favorable and similar throughout
      long-term follow-up, with a rate of prosthesis failure of less than 3%.

PMID- 29062744
TI  - Transcatheter aortic valve replacement in intermediate and low risk patients
      clinical evidence.
AB  - The encouraging results of the PARTNER 2 (Placement of AoRtic TraNscathetER
      Valves 2) trial led to the approval of transcatheter aortic valve replacement
      (TAVR) in intermediate-surgical-risk patients. Recently, the SURTAVI (SUrgical
      Replacement and Transcatheter Aortic Valve Implantation) investigators
      demonstrated the feasibility of TAVR with self-expanding valves in intermediate
      risk patients. The focus has now shifted to clinical trials comparing TAVR to
      surgery in low-surgical-risk populations with a goal to expand TAVR to all-risk
      patients. However, low-surgical-risk patients continue to be acceptable
      candidates for surgical aortic valve replacement, with proven outcomes over many
      decades. Although new data has emerged showing feasibility of TAVR in young
      patients with bicuspid valves, with newer generation TAVR valves there will be
      minimal tolerance for adverse outcomes in the low risk category. To expand the
      reach of TAVR into low-surgical-risk patients, important questions about valve
      durability, leaflet thrombosis, higher rates of paravalvular leak and permanent
      pacemakers (PPM) will need to be addressed. However, as TAVR technology continues
      to evolve, it seems to be just a matter of time before TAVR establishes itself as
      a modality for aortic valve replacement regardless of surgical risk.

PMID- 29062743
TI  - Parsimonious assessment for reoperative aortic valve replacement; the deterrent
      effect of low left ventricular ejection fraction and renal impairment.
AB  - BACKGROUND: Patient comorbidities play a pivotal role in the surgical outcomes of
      reoperative aortic valve replacement (re-AVR). Low left ventricular ejection
      fraction (LVEF) and renal insufficiency (Cr >2 mg/dL) are known independent
      surgical risk factors. Improved preoperative risk assessment can help determine
      the best therapeutic approach. We hypothesize that re-AVR patients with low LVEF
      and concomitant renal insufficiency have a prohibitive surgical risk and may
      benefit from transcatheter AVR (TAVR). METHODS: From January 2002 to March 2013,
      we reviewed 232 patients who underwent isolated re-AVR. Patients older than 80
      years were excluded to adjust for unobserved frailty. We identified 37 patients
      with a <=35% LVEF (low ejection fraction group-LEF) and 195 patients with >35%
      LVEF (High ejection fraction group-HEF). RESULTS: The mean age was 68.4+/-11.5
      years and there were more females (86.5% versus 64.1%, P=0.007) in the LEF group.
      The prevalence of renal insufficiency was higher in LEF patients (27% versus
      5.6%, P=0.001). Higher operative mortality (13.5% versus 3.1%, P=0.018) was
      observed in the LEF group. Stroke rates were similar in both groups (8.1% versus
      4.1%, P=0.39). Unadjusted cumulative survival was significantly lower in LEF
      patients (6.6 years, 95% CI: 5.2-8.0, versus 9.7 years, 95% CI: 8.9-10.4,
      P=0.024). In patients without renal insufficiency, LEF and HEF had similar
      survival (8.3 years, 95% CI: 7.1-9.5, versus 9.9 years, 95% CI: 9.1-10.6,
      P=0.90). Contrarily, in patients with renal insufficiency, LEF led to a
      significantly lower survival (1.1 years, 95% CI: 0.1-2.0, versus 4.8 years, 95%
      CI: 2.2-7.3, P=0.050). Adjusted survival analysis revealed elevations in baseline
      creatinine (HR =4.28, P<0.001) and LEF (HR =5.33, P=0.041) as significant
      predictors of long-term survival, with a significant interaction between these
      comorbidities (HR =7.28, P<0.001). CONCLUSIONS: In re-AVR patients, low LVEF
      (<=35%) is associated with increased operative mortality. Concomitant renal
      insufficiency in these patients results in a prohibitively low cumulative
      survival. These reoperative surgical outcomes should warrant expanding the role
      of TAVR for reoperative patients with LEF and renal impairment.

PMID- 29062746
TI  - Transcatheter aortic valve implantation in Asia.
AB  - The use of transcatheter aortic valve implantation (TAVI) to treat severe
      symptomatic aortic valve stenosis has increased exponentially in the last decade.
      This rapid expansion was seen predominantly in Western developed nations and has
      been fuelled by favorable results reported from a plethora of well-publicized
      randomized controlled trials, large retrospective series and national registries.
      Now, TAVI has become the standard of care for inoperable patients and an
      alternative to open surgery in patients who are at intermediate to high risk for
      open surgery. Notwithstanding these positive results, Asia has been relatively
      slow to adopt this technology despite a potentially large patient pool. Unique
      features of Asian medical environments and differences in Asian anatomy affecting
      TAVI uptake in Asia will be discussed. This article serves to outline the various
      challenging aspects of disseminating TAVI in Asian countries.

PMID- 29062745
TI  - Review of minimal access versus transcatheter aortic valve replacement for
      patients with severe aortic stenosis.
AB  - Transcatheter aortic valve replacement (TAVR) and minimally invasive aortic valve
      replacement (miniAVR) have become alternatives to surgical aortic valve
      replacement via median sternotomy (SAVR) to treat severe aortic stenosis (AS).
      Despite increased interest and utilization, few studies have directly compared
      TAVR and miniAVR. A review of the current literature shows TAVR to be an
      indispensable tool for inoperable, high-risk, and perhaps intermediate-risk
      patients with severe AS. However, it is associated with a number of deleterious
      perioperative outcomes, such as valvular regurgitation and vascular
      complications. MiniAVR is associated with decreased intensive care unit (ICU) and
      hospital length of stay, a lower incidence of blood transfusions, decreased
      ventilation time, and improved cosmetic results. MiniAVR maintains potential
      advantages over SAVR, including the implantation of a durable prosthesis and low
      rates of perioperative myocardial infarction and paravalvular leak. It is
      associated with longer aortic cross clamp and cardiopulmonary bypass (CPB) times;
      however, the use of sutureless valve implants can circumvent this. Studies
      comparing TAVR and miniAVR demonstrate decreased postoperative mortality,
      valvular regurgitation, and incidence of stroke in the miniAVR cohorts. Few
      studies currently exist comparing TAVR and miniAVR, as it is hard to compare the
      typically low-risk miniAVR versus high-risk TAVR patient populations. It is clear
      that both strategies will be cornerstones in the modern AVR era, but the
      situations in which to apply each strategy have not yet been clearly delineated.
      This highlights the need for surgeons to adopt these minimally invasive
      techniques. We believe there is a compelling role for miniAVR in low- and
      intermediate-risk patients, but due to the paucity of data, neither TAVR nor
      miniAVR should be discounted before a randomized, risk-stratified trial is
      performed. More studies are needed to compare TAVR and miniAVR in low- and
      intermediate-risk patients.

PMID- 29062747
TI  - Comparison of hemodynamic and clinical outcomes of transcatheter and sutureless
      aortic bioprostheses: how to make the right choice in intermediate risk patients.
AB  - Current surgical treatment options for aortic valve stenosis (AS), as
      alternatives to that of conventional operation with a midline sternotomy, include
      sutureless valve replacement (SUAVR) and transcatheter valve implantation (TAVI).
      Patients with high surgical risk, or those who are judged to be inoperable, are
      typically good candidates for the TAVI procedure. The best treatment option in
      patients with an intermediate risk profile, however, the so called "grey zone",
      is still currently under debate. Sutureless aortic valve replacement has been
      recently presented as a valid alternative for patients with low- to intermediate
      risk. Data available on prostheses' hemodynamic performance and patients'
      clinical outcomes play a crucial role in the process of device selection.
      Compared to TAVI, SUAVR provides lower rate of significant postoperative
      paravalvular leak (PVL), which has shown to be a predictor for mortality. On the
      contrary, transcatheter valves seem to perform better in terms of transvalvular
      mean and peak gradients. Therefore, SUAVR and TAVI are both reliable options in
      patients with severe aortic valve stenosis, as an alternative to conventional
      surgery, and the choice of the best device should be tailored to patient's
      anatomical and surgical characteristics.

PMID- 29062748
TI  - Transcatheter aortic valve implantation economics: a grisly reality.
AB  - Transcatheter aortic valve implantation (TAVI), an established treatment for
      inoperable and high-risk operable symptomatic patients with severe aortic
      stenosis with growing numbers of procedures and expanding indications, is an
      expensive therapy. Cost-effectiveness analyses rely on the value of the
      incremental cost-effectiveness ratio (ICER), which is the difference in cost
      between two possible interventions, divided by the difference in their effect.
      Several analyses have demonstrated that TAVI is cost-effective with an acceptable
      ICER for the inoperable patient alone and only via the iliofemoral route, while
      TAVI is more costly and is either less or equally effective as surgery in high
      risk operable patients. When use of TAVI is extended to include a larger number
      of patients suitable for surgery, the overall results become less favorable.
      Acceptable ICERs should practically equate to the value of the gross domestic
      product (GDP) per capita in each country; however, the cost of the TAVI kit alone
      already exceeds the GDP per capita of all moderate- and low-income countries. An
      overview of the current cost-efficacy issues of TAVI is presented and this grisly
      reality is discussed, which may hopefully be improved in the future.

PMID- 29062749
TI  - Transcatheter aortic valve implantation in nonagenarians: selectively feasible or
      extravagantly futile?
AB  - A growing number of nonagenarians is recorded as life expectancy increases.
      Unfortunately, this extreme-aged group is plagued by increased prevalence of
      aortic stenosis amidst a higher occurrence of comorbidities that pose dilemmas to
      cardiologists and cardiac surgeons when having to choose a conservative or
      interventional treatment modality, and a surgical or transcatheter aortic valve
      implantation (TAVI) approach. TAVI is an expensive procedure, which also confers
      a higher mortality and morbidity risk in nonagenarians, compared to younger
      patients. Considering the physiologic rather the chronologic age alone, and
      adopting a shared-decision making approach (participatory medicine), it may be
      more realistic to determine a patient's candidacy for this non-surgical
      therapeutic modality. Thus, it comes down to the patient selection process by
      having the heart team review each nonagenarian case individually and getting the
      patient and the family involved, always aiming to prolong and improve patient's
      quality of life (QoL), but also taking into consideration patient preferences and
      values, sharing and respecting goals, realistic expectations, and end-of-life
      views and ideas. One should keep in mind that there is always the possibility
      that TAVI may be clinically futile for patients who have a multitude of
      comorbidities and extreme frailty, for whom a transition to palliative care might
      be prudent. Selecting nonagenarian patients with low comorbidity index and with
      no extreme frailty, adopting a minimalistic approach and paying attention to
      vascular access hemostasis may provide the elements that may lead to a
      successful, desirable and hopefully cost-effective outcome.

PMID- 29062751
TI  - Those who do not remember the past are condemned to repeat it.
AB  - Transcatheter aortic valve replacement (TAVR) for aortic valve stenosis has
      rapidly progressed from its initial application in the inoperable or high-risk
      patients to those determined to be intermediate and low risk. It is our concern
      this has occurred without adequate knowledge or examination of the long-term
      durability of TAVR valves and the impact on subsequent aortic valve surgery,
      should it be required. In this editorial, we provide insight and reflect upon
      lessons learned from past surgical techniques and their subsequent abandonment.

PMID- 29062750
TI  - Impact of frailty markers on outcomes after transcatheter aortic valve
      replacement: insights from a Japanese multicenter registry.
AB  - There are no standardized criteria for measuring patients' frailty. We examined
      prognosis based on four frailty markers [serum albumin level, grip strength, gait
      speed, and clinical frailty scale (CFS)] in patients who underwent transcatheter
      aortic valve replacement (TAVR) between October 2013 and April 2016 and were
      recorded in the Optimized CathEter vAlvular iNtervention (OCEAN) Japanese
      multicenter registry. Serum albumin level was assessed by dividing patients into
      two groups: hypoalbuminemia or non-hypoalbuminemia according to their serum
      albumin level. Clinical outcomes including all-cause, cardiovascular and non
      cardiovascular mortality rates after TAVR were compared. During the follow-up
      period cumulative all-cause, cardiovascular and non-cardiovascular mortality
      rates were significantly higher in the hypoalbuminemia group than in the non
      hypoalbuminemia group. This result remained unchanged even after a propensity
      matched model was used in terms of cumulative all-cause and non-cardiovascular
      mortality; however, differences in cardiovascular mortality rates were
      attenuated. To consider the impact of grip strength patients were divided into a
      low or high peak grip strength group based on classification and regression tree
      (CART) survival analysis. The clinical outcomes for each sex were compared
      between the two groups. In both sexes the cumulative 1-year mortality rates were
      significantly different between the two groups. To investigate gait speed
      patients were classified into two gait speed groups (low or high gait speed
      group) based on CART survival analysis. Clinical outcomes were compared between
      the two groups. The cumulative 1-year mortality rate was significantly different
      between the two gait speed groups. The effect of CFS on prognosis after TAVR was
      assessed. Patients were categorized into five groups based on the following CFS
      scores: CFS1-3, CFS4, CFS5, CFS6, and CFS >=7. We evaluated the relationship
      between the CFS score and other indicators of frailty markers. We also assessed
      the mid-term mortality among the five groups. The CFS score had a significant
      correlation with other frailty markers. The cumulative 1-year mortality increased
      with an increasing CFS score. In the Cox regression multivariable analysis, the
      CFS score was an independent predictive factor of an increased late cumulative
      mortality risk. In conclusion, the results suggest that serum albumin level, grip
      strength, gait speed, and CFS score are all useful indicators when considering
      the optimal indications and risk stratification for TAVR.

PMID- 29062752
TI  - Technical pitfalls and tips for the valve-in-valve procedure.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as a viable treatment
      modality for patients with severe aortic valve stenosis and multiple co
      morbidities. More recent indications include the use of transcatheter heart
      valves (THV) to treat degenerated bioprosthetic surgical heart valves (SHV),
      which are failing due to stenosis or regurgitation. Valve-in-valve (VIV)
      procedures in the aortic position have been performed with a variety of THV
      devices, although the balloon-expandable SAPIEN valve platform (Edwards
      Lifesciences Ltd, Irvine, CA, USA) and self-expandable CoreValve platform
      (Medtronic Inc., MN, USA) have been used in majority of the patients. VIV
      treatment is appealing as it is less invasive than conventional surgery but
      optimal patient selection is vital to avoid complications such as malposition,
      residual high gradients and coronary obstruction. To minimize the risk of
      complications, thorough procedural planning is critical. The first step is
      identification of the degenerated SHV, including its model, size, fluoroscopic
      appearance. Although label size and stent internal diameter (ID) are provided by
      the manufacturer, it is important to note the true ID. The true ID is the ID of a
      SHV after the leaflets are mounted and helps determine the optimal size of THV.
      The second step is to determine the type and size of the THV. Although this is
      determined in the majority of the cases by user preference, in certain situations
      one THV may be more suitable than another. As the procedure is performed under
      fluoroscopy, the third step is to become familiarized with the fluoroscopic
      appearance of both the SHV and THV. This helps to determine the landmarks for
      optimal positioning, which in turn determines the gradients and fixation. The
      fourth step is to assess the risk of coronary obstruction. This is performed with
      either aortic root angiography or ECG-gated computerised tomography (CT).
      Finally, the route of approach must be carefully planned. Once these aspects are
      addressed, the procedure can be performed efficiently with a low risk of
      complications.

PMID- 29062753
TI  - Transapical approach for transcatheter aortic valve implantation.

PMID- 29062754
TI  - Transcarotid approach for TAVI: an optimal alternative to the transfemoral gold
      standard.

PMID- 29062755
TI  - Transcatheter aortic valve implantation (TAVI) in patients with aortic
      regurgitation.

PMID- 29062756
TI  - Transcatheter aortic valve replacement using the transaortic approach.

PMID- 29062757
TI  - Trans-subclavian approach for transcatheter aortic valve replacement.

PMID- 29062758
TI  - Transcatheter aortic valve implantation.

PMID- 29062759
TI  - People with disabilities and income-related social protection measures in South
      Africa: Where is the gap?
AB  - BACKGROUND: People with disabilities are at increased risk of poverty,
      particularly in low-and middle-income countries. However, recent evidence
      suggests that this association is more nuanced than previously anticipated and
      that we need better data to understand the opportunity and out-of-pocket costs
      that diverse groups of people with disabilities may experience. OBJECTIVE: This
      paper discusses if disability is associated with opportunity cost and loss of
      income both on the individual and household level in South Africa, and if these
      costs differ depending on disability type and severity. METHODS: For this
      purpose, the paper analyses General Household Survey 2011 data (people between 15
      and 59) using descriptive statistics disaggregated via disability type and
      severity. The paper also assesses if social grants counteract these costs and
      reduce economic vulnerability. RESULTS: The analysis of the data reveals that
      people with disabilities are affected by issues relating to multidimensional
      poverty such as lower educational attainment and fewer employment opportunities.
      In addition, households of people with disabilities (with the exception of milder
      visual problems) earn significantly less than households without people with
      disabilities, and this particularly applies to households with people with severe
      disabilities. This vulnerability also varies by disability type. The country's
      social protection mechanisms, in terms of social grants, counteract economic
      vulnerability to some extent but do not consider the nuanced economic impact of
      diverse conditions nor the increased out-of-pocket costs related to disability.
      CONCLUSIONS: This calls for more equitable social protection mechanisms that
      include accessible services, livelihood programmes and disability benefits.

PMID- 29062761
TI  - Wheelchair accessibility to public buildings in the Kumasi metropolis, Ghana.
AB  - BACKGROUND: Accessibility implies making public places accessible to every
      individual, irrespective of his or her disability or special need, ensuring the
      integration of the wheelchair user into the society and thereby granting them the
      capability of participating in activities of daily living and ensuring equality
      in daily life. OBJECTIVE: This study was carried out to assess the accessibility
      of the physical infrastructures (public buildings) in the Kumasi metropolis to
      wheelchairs after the passage of the Ghanaian Disability Law (Act 716, 2006).
      METHODS: Eighty-four public buildings housing education facilities, health
      facilities, ministries, departments and agencies, sports and recreation,
      religious groups and banks were assessed. The routes, entrances, height of steps,
      grade of ramps, sinks, entrance to washrooms, toilets, urinals, automated teller
      machines and tellers' counters were measured and computed. RESULTS: Out of a
      total of 84 buildings assessed, only 34 (40.5%) of the buildings, 52.3% of the
      entrances and 87.4% of the routes of the buildings were accessible to wheelchair
      users. A total of 25% (13 out of 52) of the public buildings with more than one
      floor were fitted with elevators to connect the different levels of floors.
      CONCLUSION: The results of this study show that public buildings in the Kumasi
      metropolis are not wheelchair accessible. An important observation made during
      this study was that there is an intention to improve accessibility when buildings
      are being constructed or renovated, but there are no laid down guidelines as how
      to make the buildings accessible for wheelchair users.

PMID- 29062760
TI  - The experiences and challenges faced by rehabilitation community service
      therapists within the South African Primary Healthcare health system.
AB  - BACKGROUND: Twenty-two years after the promulgation of a plethora of progressive
      health policies since 1994, the South African public health system reflects a
      number of stumbling blocks regarding implementation. Rehabilitation professionals
      are not sufficiently equipped nor allowed the opportunity to comprehensively
      implement Primary Healthcare (PHC) from a bottom-up approach, thus engaging
      communities. Training on addressing social health determinants and their impact
      on ill-health and health outcomes is inadequate. The inadequate understanding of
      the advocacy role that rehabilitation professionals could play in addressing
      social health determinants remains a challenge in healthcare. Rehabilitation, a
      pillar of PHC, remains poorly understood in terms of its role within the health
      system. AIM: We argue for rehabilitation as a vehicle for addressing social
      determinants of health with community service practitioners playing a critical
      role in addressing the inequities within the healthcare package. SETTING: The
      article reflects the opportunities and challenges faced by rehabilitation
      community service therapists in the delivery of rehabilitation services in a
      rural area of the Eastern Cape province of South Africa. METHODS: A single case
      study from the perspective of a researcher was used to explore the experience and
      reflection of the first author during her community service as an occupational
      therapist. RESULTS: The case study highlights some existing gaps within the
      delivery of rehabilitation services in the rural Eastern Cape. A community
      service package with a specific approach towards addressing social determinants
      of health for persons with disability at a community level is suggested.
      CONCLUSION: Advocating for a rehabilitation service package to shift to community
      based levels is critical. It is envisaged that a community-based approach will
      facilitate an understanding of the barriers faced by persons with disabilities as
      constituting disability, thus facilitating learning about the disabling
      consequences of the rural environment coupled with the system as experienced by
      persons with disabilities.

PMID- 29062762
TI  - Development of wheelchair caster testing equipment and preliminary testing of
      caster models.
AB  - BACKGROUND: Because of the adverse environmental conditions present in less
      resourced environments (LREs), the World Health Organization (WHO) has
      recommended that specialised wheelchair test methods may need to be developed to
      support product quality standards in these environments. A group of experts
      identified caster test methods as a high priority because of their common failure
      in LREs, and the insufficiency of existing test methods described in the
      International Organization for Standardization (ISO) Wheelchair Testing Standards
      (ISO 7176). OBJECTIVES: To develop and demonstrate the feasibility of a caster
      system test method. METHOD: Background literature and expert opinions were
      collected to identify existing caster test methods, caster failures common in
      LREs and environmental conditions present in LREs. Several conceptual designs for
      the caster testing method were developed, and through an iterative process using
      expert feedback, a final concept and a design were developed and a prototype was
      fabricated. Feasibility tests were conducted by testing a series of caster
      systems from wheelchairs used in LREs, and failure modes were recorded and
      compared to anecdotal reports about field failures. RESULTS: The new caster
      testing system was developed and it provides the flexibility to expose caster
      systems to typical conditions in LREs. Caster failures such as stem bolt
      fractures, fork fractures, bearing failures and tire cracking occurred during
      testing trials and are consistent with field failures. CONCLUSION: The new caster
      test system has the capability to incorporate necessary test factors that degrade
      caster quality in LREs. Future work includes developing and validating a testing
      protocol that results in failure modes common during wheelchair use in LRE.

PMID- 29062763
TI  - Adaptation of the curriculum for the inclusion of learners with special education
      needs in selected primary schools in the Fort Beaufort District.
AB  - BACKGROUND: There is need for 'high-quality' teachers who are equipped to meet
      the needs of all learners through provision of education for an inclusive society
      according to equal opportunities to all. OBJECTIVE: This paper investigates
      pockets of good practice in the adaptation of the curriculum for the inclusion of
      learners with special education needs (SEN) in selected primary schools in the
      Fort Beaufort District. METHOD: The study adopted a qualitative research approach
      and employed a case study design. Eight teachers and 10 principals from 10
      selected primary schools, 4 education district officials and 1 provincial
      official were interviewed. Purposive sampling was used to select the
      participants. Data were collected using document analysis and semi-structured
      interviews and were analysed thematically. RESULT: The study established that
      teachers use methods relating to different teaching strategies, individual work,
      group work and extra work. CONCLUSION: It was concluded that there are pockets of
      good practice of inclusion policy such as the use of different teaching
      strategies, individual work, group work and extra work for inclusion of learners
      with SEN in some of the selected primary schools in the poor rural context. The
      paper recommends adequate training for teachers in curriculum adaptation in order
      for all teachers to accommodate learners with SEN.

PMID- 29062764
TI  - Gastrodin protects retinal ganglion cells through inhibiting microglial-mediated
      neuroinflammation in an acute ocular hypertension model.
AB  - AIM: To investigate the neuroprotective effect of gastrodin on retinal ganglion
      cells (RGCs) in an acute ocular hypertension (AOH) rat model and to identify its
      possible mechanism. METHODS: AOH rat model was performed in a randomly selected
      eye by anterior chamber perfusion and either received an intraperitoneal
      injection with various concentrations of gastrodin or normal saline. After 2wk,
      the rats were sacrificed. FluoroGold was used to label survival RGCs.
      Immunostaining with anti-Iba1 in the retinal flat mounts to calculate the
      microglia density in the ganglion cell layer (GCL). Changes in microglial
      cytokines, tumour necrosis factor-alpha (TNF-alpha) and inducible NO synthase
      (iNOS) were examined with Western blot and reverse transcription-quantitative
      polymerase chain reaction. Expression levels of total and phosphorylated p38
      mitogen activated protein kinase (MAPK) were determined by Western blot. RESULTS:
      Results showed that AOH induced significant loss of RGCs and severe microglia
      activation in the GCL. Besides, AOH increased the phosphorylation of p38 MAPK and
      promoted the release of microglial cytokines in the retinas. Intraperitoneal
      injection with dose-dependent gastrodin significantly reduced the loss of RGCs
      and inhibited retinal microglia activation, accompanied with the decreased
      expression levels of microglial cytokines and p38 MAPK phosphorylation.
      CONCLUSION: Gastrodin exerts a neuroprotective effect on RGCs in an acute
      glaucoma animal model via inhibiting microglia activation and microglial-mediated
      neuroinflammation. The finding demonstrates the potential application of
      gastrodin in the neuroprotective therapy of acute glaucoma and other retinal
      neurodegenerative diseases characterized by microglia activation and RGCs death.

PMID- 29062765
TI  - Genes of tumor necrosis factors and their receptors and the primary open angle
      glaucoma in the population of Central Russia.
AB  - AIM: To examine the association of genetic polymorphisms (-308)G/A TNFalpha,
      (+250)A/G Ltalpha, (+36)A/G TNFR1, (+1663)A/G TNFR2 with the development of
      primary open angle glaucoma (POAG) among people in Central Russia. METHODS: The
      study sample included 443 individuals, of which 252 patients with POAG and 191
      individuals in the control group. Genotyping of (-308)G/A TNFalpha, (+250)A/G
      Ltalpha, (+36)A/G TNFR1, (+1663)A/G TNFR2 was performed using polymerase chain
      reaction. The distribution of alleles and genotypes of the studied DNA markers in
      the groups was examined by 2*2 contingency tables and chi2 with the Yates's
      correction for continuity and odds ratios (OR) with 95% confidence intervals
      (CI). RESULTS: Allele (-308)G TNFalpha (R=0.01, OR=1.78, 95%CI 1.12-2.85) was
      identified as a risk factor for POAG. Homozygotes (-308) AA TNFalpha are at a
      lowest risk for development of the disease (R=0.01, OR=0.0005). The following
      combination of genetic variants of cytokines were associated with a reduced risk
      of POAG: (+1663)A TNFR2 and (+250)G Ltalpha (OR=0.34). CONCLUSION: Genetic
      polymorphisms (-308)G/A TNFalpha, (+250)A/G Ltalpha, (+1663)A/G TNFR2 associated
      with the development of POAG in the population of Central Russia.

PMID- 29062766
TI  - The reason for the amelioration of N-methyl-N-nitrosourea-induced retinitis
      pigmentosa in rats by hydrogen-rich saline.
AB  - AIM: To investigate the effects of hydrogen-rich saline (HRS) on microglia
      activation and Sirtuin type 1 (Sirt1) in rats with N-methyl-N-nitrosourea (MNU)
      induced retinitis pigmentosa (RP). METHODS: Rats were divided into norm (N)
      group, model (M) group and HRS (H) group. Rats in M and H groups were given
      saline and HRS respectively prior to and after administration of MNU. At one day
      (d1) and d3 afterwards, electroretinogram and histological examination were
      performed to confirm the effects of HRS on retinal function and structure of MNU
      induced RP. Immunofluorescence staining of anti-ionized calcium-binding adapter
      molecule 1 (Iba1), a maker of microglia cells, was performed, with quantitative
      real-time polymerase chain reaction (qRT-PCR) for its mRNA quantification.
      Moreover, Sirt1 mRNA and protein expression in the retinas were detected by
      Western blot and qRT-PCR. RESULTS: HRS preserved the retinal function and
      mitigated the reduction of photoreceptor degeneration in MNU-treated retinas. The
      presence of microglia cells was somewhat more obvious in H group than that in M
      group at d1. HRS suppressed the further activation of microglia cells, with the
      number of microglia cells less than that of M group at d3. Results of qRT-PCR of
      Iba1 were consistent with those of immunofluorescence staining, with the mRNA
      expression of Iba1 in H group more intensive than that of M group at d1 (P<0.05),
      while less than that of M group at d3 (P<0.05). Furthermore, the Sirt1 mRNA and
      protein expression decreased after MNU administration, while HRS mitigated the
      MNU-induced downregulation of Sirt1. CONCLUSION: HRS can effectively keep
      microglia activation induced by MNU to an appropriate extent, while upregulate
      Sirt1 in MNU-induced RP.

PMID- 29062767
TI  - Differentiation of human olfactory mucosa mesenchymal stem cells into
      photoreceptor cells in vitro.
AB  - AIM: To investigate whether the human olfactory mucosa mesenchymal stem cells (OM
      MSCs) can differentiate into photoreceptor cells in vitro. METHODS: Through the
      olfactory mucosa adherent method, olfactory mucosa was isolated, cultured and
      identified in vitro among mesenchymal stem cells. The cell surface markers were
      analyzed by flow cytometry, induced to differentiate into retinal photoreceptor
      cells in vitro, and the expression of rhodopsin was observed and identified by
      Immunofluorescence and Western blot methods. RESULTS: OM-MSCs from human were
      spindle cell-based, and showing radial colony arrangement. OM-MSCs were negative
      for CD34, CD45 and CD105, but positive for CD73 and CD90. Following induction, a
      strong positive reaction was produced by photoreceptor specific marker rhodopsin
      in the cells. CONSLUSION: This novel finding demonstrates that OM-MSCs can be
      cultured and expanded in vitro. They possess biological characteristics of
      mesenchymal stem cells, and have the ability to be induced into retinal cells.

PMID- 29062768
TI  - Expressions of nestin and glial fibrillary acidic protein in rat retina after
      optic nerve transection.
AB  - AIM: To assess the expression of nestin and glial fibrillary acidic protein
      (GFAP) in rat retina after optic nerve transection. METHODS: Rats were randomly
      divided into normal control group, sham group and operation group, and used for
      establishing an animal model of optic nerve transection. Retinal specimen of each
      group was collected at 3, 48h, 7 and 14d postoperative. Nestin and GFAP
      expressions on sagittal sections were analyzed by immunohistochemical staining,
      and protein extraction was analyzed by Western blot. RESULTS: Immunohistochemical
      analysis showed that nestin positive staining was rarely detected in normal
      control group and sham group, while sham group showed weak positive staining at
      3h postoperative, the reaction gradually increased at 48h postoperative, and
      reached its maximum at 7d postoperative, and then decreased at 14d postoperative.
      Compared to the expression of GFAP, there was not statistically significant
      obvious difference among three groups (P>0.05). Result of Western blot method was
      consistent with that of immunohistochemical method. CONCLUSION: The expression of
      nestin increased in a time dependent fashion in Muller cells of retina following
      optic nerve transection, which was statistically significant, but there was no
      obvious difference in GFAP expression. The results indicate that an increase in
      colloid synthesis in retina following optic nerve transection can improve the
      retinal neurons' environment.

PMID- 29062769
TI  - The association of lumican polymorphisms and high myopia in a Southern Chinese
      population.
AB  - AIM: To investigate the correlation between lumican (LUM) gene and high myopia in
      a Southern Chinese population. METHODS: The study comprised of 95 high myopia
      patients with a spherical equivalent <=-6.5 diopters (D). The control group
      recruited 95 individuals with a spherical equivalent ranging from -0.5 D to +0.5
      D. Direct sequencing was used to detect the single nucleotide polymorphisms
      (SNPs) of LUM gene in coding region. Genotype distributions were tested for Hardy
      Weinberg disequilibrium. Genotypic and allelic frequencies were analyzed through
      Chi-square test or Fisher's exact test. RESULTS: We identified 3 SNPs of the LUM
      gene: LUM c.32 (rs577456426), LUM c.507 (rs17853500) and LUM c.849 (rs181915277).
      Among the three SNPs, the genotype and allele frequencies of rs17853500 showed a
      significant difference between patients and control subjects (P<0.05). However,
      there were no significant differences in rs181915277 and rs577456426 between the
      two groups (P>0.05). CONCLUSION: LUM c.507 polymorphism may be a risk factor for
      the pathogenesis of high myopia in the Southern Chinese population.

PMID- 29062770
TI  - Dependence of dynamic contour and Goldmann applanation tonometries on peripheral
      corneal thickness.
AB  - AIM: To determine the effects of peripheral corneal thickness (PCT) on dynamic
      contour tonometry(DCT) and Goldmann applanation tonometry (GAT). METHODS: A cross
      sectional study. We created a software which calculates the corneal contour (CC)
      as a function of the radius from the corneal apex to each pixel of the contour.
      The software generates a central circumference with a radius of 1 mm and the
      remainder of the cornea is segmented in 5 rings concentric with corneal apex
      being its diameter not constant around the corneal circumference as a consequence
      of the irregular CC but keeping constant the diameter of each ring in each
      direction of the contour. PCT was determined as the mean thickness of the most
      eccentric ring. Locally weighted scatterplot smoothing (LOWESS) regression was
      used to determine the pattern of the relationship between PCT and both DCT and
      GAT respectively. Thereafter, two multivariable linear regression models were
      constructed. In each of them, the dependant variable was intraocular pressure
      (IOP) as determined using GAT and DCT respectively. In both of the models the
      predictive variable was PCT though LOWESS regression pattern was used to model
      the relationship between the dependant variables and the predictor one. Age and
      sex were also introduced control variables along with their first-degree
      interactions with PCT. Main outcome measures include amount of IOP variation
      explained through regression models (R2) and regression coefficients (B).
      RESULTS: Subjects included 109 eyes of 109 healthy individuals. LOWESS regression
      suggested that a 2nd-degree polynomial would be suitable to model the
      relationship between both DCT and GAT with PCT. Hence PCT was introduced in both
      models as a linear and quadratic term. Neither age nor sex nor interactions were
      statistically significant in both models. For GAT model, R2 was 17.14% (F=9.02;
      P=0.0002), PCT linear term B was -1.163 (95% CI: -1.163, -0.617). PCT quadratic
      term B was 0.00081 (95% CI: 0.00043, 0.00118). For DCT model R2 was 14.28%
      (F=9.29; P=0.0002), PCT linear term B was -0.712 (95% CI: -1.052, -0.372), PCT
      quadratic term was B=0.0005 (95% CI: 0.0003, 0.0007). CONCLUSION: DCT and GAT
      measurements are conditioned by PCT though this effect, rather than linear,
      follows a 2nd-degree polynomial pattern.

PMID- 29062771
TI  - Postoperative visual performance with a bifocal and trifocal diffractive
      intraocular lens during a 1-year follow-up.
AB  - AIM: To evaluate and compare the clinical outcomes with a diffractive bifocal and
      trifocal intraocular lens (IOL) during a 12-month follow-up. METHODS: Prospective
      comparative study including 75 eyes of 38 patients (44-70y) undergoing uneventful
      cataract surgery. Each patient was randomly assigned to one type of IOL, bifocal
      (35 eyes) or trifocal (40 eyes). Visual, refractive, and contrast sensitivity
      changes were evaluated in a 12-month follow-up. The binocular defocus curve was
      also measured at 12mo postoperatively. RESULTS: No statistically significant
      differences between groups were found in postoperative uncorrected and corrected
      distance visual acuities (P>=0.276). Postoperative corrected near visual acuity
      (33 cm) was significantly better in the trifocal group during all follow-up
      (P<=0.004) as well as 6-month uncorrected near (P=0.008) and distance-corrected
      near visual acuities (P=0.016) (33/40 cm). Significantly better uncorrected
      intermediate and distance corrected-intermediate visual acuity were found during
      all follow-up in the trifocal group (P<0.001), which was consistent with
      differences among groups in binocular defocus curve. Differences among groups in
      contrast sensitivity were minimal, being only significant at 6 months for some
      low to medium spatial frequencies (P<=0.006). CONCLUSION: Bifocal and trifocal
      diffractive IOLs are able to provide an effective visual restoration which is
      maintained during a 12-month follow-up, with a clear benefit of the trifocal IOL
      for the intermediate vision.

PMID- 29062772
TI  - Structure-function relationship comparison between retinal nerve fibre layer and
      Bruch's membrane opening-minimum rim width in glaucoma.
AB  - AIM: To evaluate and compare structural optical coherence tomography (OCT)-based
      parameters, such as Bruch's membrane opening-minimum rim width (BMO-MRW), and
      retinal nerve fiber layer (RNFL) thickness in glaucoma patients with visual field
      (VF) defects, and to correlate both to mean deviation (MD) values of obtained
      standard achromatic perimetry (SAP) examinations. METHODS: Patients with glaucoma
      and glaucomatous VF defects were enrolled in this prospective study and compared
      to age-matched healthy individuals. All study participants underwent a full
      ophthalmic examination and VF testing with SAP. Peripapillary RNFL thickness and
      BMO-MRW were acquired with SD-OCT. Correlation analyses between obtained global
      functional and global as well as sectorial structural parameters were calculated.
      RESULTS: A consecutive series of 30 glaucomatous right eyes of 30 patients were
      included and compared to 36 healthy right eyes of 36 individuals in the control
      group. Global MD of values correlated significantly with global RNFL (Pearson
      corr. coeff: 0.632, P=0.001) and global BMO-MRW (Pearson corr. coeff: 0.746,
      P<0.001) values in the glaucoma group. Global MD and sectorial RNFL or BMO-MRW
      values correlated less significantly. In the control group, MD values did not
      correlate with RNFL or BMO-MRW measurements. A subgroup analysis of myopic
      patients (>4 diopters) within the glaucoma group (n=6) revealed a tendency for
      higher correlations between MD and BMO-MRW than MD and RNFL measurements.
      CONCLUSION: In a clinical setting, RNFL thickness and BMO-MRW correlate similarly
      with global VF sensitivity in glaucoma patients with BMO-MRW showing higher
      correlations in myopic glaucoma patients.

PMID- 29062773
TI  - Optical coherence tomography with or without enhanced depth imaging for
      peripapillary retinal nerve fiber layer and choroidal thickness.
AB  - AIM: To assess peripapillary retinal nerve fiber layer (RNFL) and choroidal
      thickness obtained with enhanced depth imaging (EDI) mode compared with those
      obtained without EDI mode using Heidelberg Spectralis optical coherence
      tomography (OCT). METHODS: Fifty eyes of 25 normal healthy subjects and 32 eyes
      of 20 patients with different eye diseases were included in the study. All
      subjects underwent 3.4 mm diameter peripapillary circular OCT scan centered on
      the optic disc using both the conventional and the EDI OCT protocols. The
      visualization of RNFL and choroidoscleral junction was assessed using an ordinal
      scoring scale. The paired t-test, intraclass correlation coefficient (ICC), 95%
      limits of agreement (LoA), and Bland and Altman plots were used to test the
      agreement of measurements. RESULTS: The visibility score of RNFL obtained with
      and without EDI was of no significant difference (P=0.532), the visualization of
      choroidoscleral junction was better using EDI protocol than conventional protocol
      (P<0.001). Peripapillary RNFL thickness obtained with EDI was slightly thicker
      than that obtained without EDI (103.25+/-9.42 um vs 101.87+/-8.78 um, P=0.010).
      The ICC of the two protocols was excellent with the value of 0.867 to 0.924, the
      95% LoA of global RNFL thickness was between -10.0 to 7.4 um. Peripapillary
      choroidal thickness obtained with EDI was slightly thinner than that obtained
      without EDI (147.23+/-51.04 um vs 150.90+/-51.84 um, P<0.001). The ICC was also
      excellent with the value of 0.960 to 0.987, the 95% LoA of global choroidal
      thickness was between -12.5 to 19.8 um. CONCLUSION: Peripapillary circular OCT
      scan with or without EDI mode shows comparable results in the measurement of
      peripapillary RNFL and choroidal thickness.

PMID- 29062774
TI  - Foveal avascular zone area and parafoveal vessel density measurements in
      different stages of diabetic retinopathy by optical coherence tomography
      angiography.
AB  - AIM: To investigate foveal avascular zone (FAZ) and parafoveal vessel densities
      (PRVD) by means of optical coherence tomography angiography (OCTA) in diabetic
      patients with or without diabetic retinopathy (DR) and to assess the
      reproducibility of FAZ and PRVD measurements. METHODS: Sixty diabetic patients
      (60 eyes) with different stage of DR (graded according to the International
      Clinical Severity Scale for DR) and 20 healthy subjects underwent FAZ area and
      PRVD measurements using OCTA by two experienced examiners. FAZ area in all
      patients was also assessed using fluorescein angiography (FA). RESULTS: In
      subject with proliferative DR and with moderate-severe non proliferative DR, FAZ
      area was significantly increased compared to healthy controls (P=0.025 and
      P=0.050 respectively measured with OCTA and P=0.025 and P=0.048 respectively
      measured with FA). OCTA showed significantly less inter-observer variability
      compared to FA. Concordance correlation coefficient (CCC) for FAZ area
      measurements was 0.829 (95%CI: 0.736-0.891) P<0.001 with FA and 1.000 (95%CI:
      0.999-1.000) P<0.001 with OCTA. CCC was 0.834 (95%CI: 0.746-0.893) P<0.001 and
      0.890 (95%CI: 0.828-0.930) P<0.001 for parafoveal superficial and deep vessel
      density measurements, respectively. CONCLUSION: OCTA shows progressive increase
      of FAZ area and reduction of PRVD in both superficial and deep plexus at
      increasing DR severity. FAZ area and PRVD measurements using OCTA are highly
      reproducible.

PMID- 29062775
TI  - Evaluating role of bone marrow-derived stem cells in dry age-related macular
      degeneration using multifocal electroretinogram and fundus autofluorescence
      imaging.
AB  - AIM: To evaluate the role of bone marrow-derived stem cells in the treatment of
      advanced dry age-related macular degeneration (AMD) using multifocal
      electroretinogram (mf-ERG) and fundus autofluorescence imaging. METHODS: Thirty
      patients (60 eyes) with bilateral central geographic atrophy (GA) were recruited.
      Worse eye of each patient received autologous bone marrow-derived hematopoietic
      stem cells (BM-HSCs) (group 1) and the fellow eye with better visual acuity
      served as control (group 2). The effect of stem cell therapy was determined in
      terms of visual acuity, amplitude and implicit time in mf-ERG and size of GA on
      fundus autofluorescence imaging. These tests were performed at presentation and
      first, third and sixth month follow up. Adverse events (if any) were also
      monitored. RESULTS: At 6mo follow-up there was no statistically significant
      improvement in median logMAR best corrected visual acuity (BCVA) in either group.
      Mf-ERG revealed significant improvement in amplitude and implicit time in the
      intervention group. A significant decrease was also noted in greatest linear
      dimension (GLD) of GA in the eyes receiving stem cells [6.78+/-2.60 mm at
      baseline to 6.56+/-2.59 mm at 6mo (P=0.021)]. However, no such improvement was
      noted in the control group. CONCLUSION: Electrophysiological and anatomical
      improvement in the intervention group sheds light on the therapeutic role of BM
      HSCs. Further studies are required to determine the stage of disease at which the
      maximal benefit can be achieved and to standardize the dose and frequency of stem
      cell injection.

PMID- 29062776
TI  - Evaluation of refractive correction for standard automated perimetry in eyes
      wearing multifocal contact lenses.
AB  - AIM: To evaluate the refractive correction for standard automated perimetry (SAP)
      in eyes with refractive multifocal contact lenses (CL) in healthy young
      participants. METHODS: Twenty-nine eyes of 29 participants were included.
      Accommodation was paralyzed in all participants with 1% cyclopentolate
      hydrochloride. SAP was performed using the Humphrey SITA-standard 24-2 and 10-2
      protocol under three refractive conditions: monofocal CL corrected for near
      distance (baseline); multifocal CL corrected for distance (mCL-D); and mCL-D
      corrected for near vision using a spectacle lens (mCL-N). Primary outcome
      measures were the foveal threshold, mean deviation (MD), and pattern standard
      deviation (PSD). RESULTS: The foveal threshold of mCL-N with both the 24-2 and 10
      2 protocols significantly decreased by 2.2-2.5 dB (P<0.001), while that of mCL-D
      with the 24-2 protocol significantly decreased by 1.5 dB (P=0.0427), as compared
      with that of baseline. Although there was no significant difference between the
      MD of baseline and mCL-D with the 24-2 and 10-2 protocols, the MD of mCL-N was
      significantly decreased by 1.0-1.3 dB (P<0.001) as compared with that of both
      baseline and mCL-D, with both 24-2 and 10-2 protocols. There was no significant
      difference in the PSD among the three refractive conditions with both the 24-2
      and 10-2 protocols. CONCLUSION: Despite the induced mydriasis and the optical
      design of the multifocal lens used in this study, our results indicated that,
      when the dome-shaped visual field test is performed with eyes with large pupils
      and wearing refractive multifocal CLs, distance correction without additional
      near correction is to be recommended.

PMID- 29062777
TI  - Comparison of visual performance recovery after thin-flap LASIK with 4
      femtosecond lasers.
AB  - AIM: To compare the speed of visual recovery following myopic thin-flap LASIK
      with four femtosecond lasers. METHODS: Eighty-eight eyes of 46 patients who were
      consecutively scheduled for bilateral LASIK with the IntraLase FS60 (Group 1),
      Femto LDV Crystal Line (Group 2), Wavelight FS200 (Group 3) and VisuMax (Group 4)
      femtosecond lasers were enrolled in. Monocular uncorrected distance visual acuity
      (UDVA), best-corrected distant visual acuity (CDVA), refraction, contrast
      sensitivity and higher-order aberrations (HOAs) were evaluated at 1, 3d, 1wk and
      1mo postoperatively. RESULTS: Sixteen eyes (72.7%) achieved 20/16 and 8 eyes
      (36.4%) were 20/12.5 at 1d in Group 2, which was significantly more than other 3
      groups. At 1wk, 20 eyes (90.9%) achieved 20/16 in Groups 2 and 4. At 1mo, 20 eyes
      (90.9%) achieved 20/16 in Group 2 and Group 4, which were significantly more than
      other two groups. While by 1 mo, the difference of the residual spherical
      equivalent (SE) was not statistically significant among 4 groups (P=0.121). The
      induction of spherical aberration (SA) were significantly less for Groups 2, 3, 4
      than for Group 1 one day after surgery (P=0.015). The differences among 4 groups
      were not statistically significant before and after surgery on every time points
      (all P>0.05). CONCLUSION: The thin-flap LASIK procedure using the Femto LDV
      Crystal Line and VisuMax femtosecond laser show faster visual performance
      recovery.

PMID- 29062778
TI  - Changes in intraocular pressure and central corneal thickness during pregnancy: a
      systematic review and Meta-analysis.
AB  - AIM: To conduct a Meta-analysis for investigating the variations in intraocular
      pressure (IOP) and central corneal thickness (CCT) during normal pregnancy.
      METHODS: We searched for clinical trials published up to November 2015 without
      language or region restrictions in PubMed, EMBASE, Web of Science, the Cochrane
      Central Register of Controlled Trials, Ovid, EBSCO, Elsevier, the Chinese
      Biomedicine Database, WanFang, CNKI, CQVIP and Google Scholar. Studies of the
      ocular changes observed in pregnant women were selected. The main outcomes were
      assessed by changes in IOP and CCT. RESULTS: Fifteen studies were included. In
      subgroup analyses, IOP was significantly decreased during the second MD=-1.53,
      95%CI (-2.19, -0.87); P<0.00001, and third MD=-2.91, 95%CI (-3.74, -2.08);
      P<0.00001 trimesters of pregnancy. CCT was increased during the second MD=10.12,
      95%CI (2.01, 18.22); P=0.01, trimester of pregnancy; moreover, during the third
      trimester of pregnancy, the CCT displayed an increasing trend, but the difference
      was not significant MD=5.98, 95%CI (-1.11, 13.07); P=0.1. CONCLUSION: A decrease
      in IOP is accompanied by an increase in CCT in the second and third trimesters of
      a normal pregnancy in women.

PMID- 29062779
TI  - Understanding practice patterns of glaucoma sub-specialists in India.
AB  - AIM: To obtain information on the prevailing practice patterns of glaucoma
      specialists in India. METHODS: Glaucoma specialists attending the Annual
      Conference of the Glaucoma Society of India (GSI) were surveyed. This survey,
      conducted in 2013, was based on an interactive audience response system. RESULTS:
      The information was obtained from 146 glaucoma specialists. Approximately half
      (n=83; 57%) had >=10y of experience in managing glaucoma and were in
      institutional practice (n=74, 51%). Goldmann applanation tonometry was preferred
      by 103 (72%) specialists whilst n=25 (17.4%) used non-contact tonometer.
      Indentation gonioscopy was favoured by two-thirds (n=90, 66%) whereas
      stereoscopic optic disc examination and visual fields using Humphrey perimeter
      was performed by a majority of the specialists surveyed (n=115, 86% and n=114;
      83% respectively). Nearly three quarter specialists (n=96; 72%) preferred optical
      coherence tomography for imaging. The primary choice for treatment of angle
      closure disease and primary open angle glaucoma was laser (iridotomy, n=117; 93%)
      and medical management (prostaglandin analogue, n=104; 78%), respectively.
      Approximately only a third of the specialists surveyed (n=37; 28%) were
      performing both trabeculectomy and implantation of a glaucoma drainage device and
      about half (n=64; 47%) were not operating on congenital glaucoma at all.
      CONCLUSION: This survey has found conformance with preferred practice patterns in
      several areas of diagnosis and management of glaucoma, but there was diversity in
      a few areas. The information is a significant step towards improvement of
      glaucoma care in India, including planning for future strategies.

PMID- 29062780
TI  - The 100 most influential papers about cataract surgery: a bibliometric analysis.
AB  - AIM: To identify the 100 most cited papers in cataract surgery, we performed a
      comprehensive bibliometric analysis basing on the literature search on the
      Thomson Reuters Web of Knowledge. METHODS: The number of citations, including the
      total citations, latest 5y citations and average citation number per year (ACY),
      authorship, year of publication, major topics, journal of publication, country
      and institution of origin of each paper were recorded and then analyzed.
      Pearson's correlation analysis was conducted to evaluate the correlation between
      the published year and the number of citations. The correlation between journal's
      impact factor (IF) and number of citations was assessed as well. RESULTS: The
      most cited paper was the classic paper done by the European Society of Cataract &
      Refractive Surgeons (ESCRS) group. This paper focused on the topic of
      endophthalmitis. Not only the most cited papers originated from the USA, but also
      some American institutions like Johns Hopkins University, Harvard Medical School,
      etc. had the most citations. Pearson's correlation analysis indicated that the
      latest 5y citations and ACY were significantly related with the published year
      (5y citations: r=0.615, P<0.001; ACY: r=0.657, P<0.001), whereas no association
      between the total number of citations and published year was found (r=0.045).
      Moreover, the IFs of journals were found to have no significant effect on the
      number of total citations. CONCLUSION: To our knowledge, this is the first study
      on the most influential papers in cataract surgery after a comprehensive research
      of relevant literatures. The present work may provide us concise information
      concerning the development history of cataract surgery over the past 66y.

PMID- 29062783
TI  - In situ cornea harvesting through the Red Cross Organization: a new approach to
      relieving severe cornea donor shortage in Chinese eye banks.
AB  - Corneal diseases are currently the second main cause of blindness in China.
      Although most of the corneal blindness could be treated by corneal
      transplantation, only about 10 000 operations were carried out each year owing to
      the severe shortage of corneal donors and limited eye bank programs. A feasible
      cornea donation program was established through the organization of the Red
      Cross, and in situ corneal removal techniques were developed to avoid conflicts
      with Chinese traditions of keeping the deceased intact. The number of donated
      corneas, which had a safe and secure quality, increased significantly year by
      year.

PMID- 29062782
TI  - The impact of combined oral contraceptives on ocular tissues: a review of ocular
      effects.
AB  - The aim of this manuscript is to review the action and adverse effects of
      combined oral contraceptives (COCs) on ocular tissues. The percentage of unwanted
      pregnancies and the subsequent abortions make contraception crucial worldwide.
      Over 100 million women around the world use common contraceptive methods,
      including intrauterine devices, combined estrogen and progestin oral
      contraceptives, as well as progestin only preparations (oral contraceptives,
      implants or injections). COCs are widely used for contraception, but they are
      also indicated in menorrhagia, endometriosis, acne and hirsutism, fibroid uterus
      and premenstrual syndrome. However, they have been associated with high rates of
      cardiovascular events, venous thromboembolic disease, ischemic strokes and breast
      cancer. The incidence of COCs-related ocular complications is estimated to be 1
      in 230 000, including dry eye symptoms, corneal edema, lens opacities and retinal
      neuro-ophthalmologic or vascular complications. We may infer that the serious
      ocular complications of COCs can be prevented by eliminating the estrogen dosage
      and choosing third-generation progestins. In any case, doctors should take into
      consideration the systemic and ocular history of the patients before selecting
      any method of contraception.

PMID- 29062784
TI  - Evaluation of the iridocorneal angle with accommodation using optical coherence
      tomography.
AB  - The changes in the iridocorneal angle structure during accommodation are assessed
      by means of anterior segment optical coherence tomography. Thirteen right eyes
      were included in the study. The device used for the measurement was the
      Visante(r)omni system. The stimuli were set up at different vergences (0.0 D, 
      1.5 D, and -3.0 D). The angle opening distance 500 and 750, the trabecular iris
      space area 500 and 750, and the scleral spur angle parameters were assessed at
      the nasal and temporal regions. The results in the iridotrabecular angle
      comparing the three accommodative states of the eye did not yield any
      statistically significant difference at nasal or temporal angle sections. In
      light of our results and in the conditions of our study, the structures of the
      iridocorneal angle are not significantly changed with accommodation.

PMID- 29062781
TI  - Paediatric retinal detachment: a review.
AB  - Paediatric retinal detachment (PRD) is an uncommon and challenging disease; it
      differs from adult detachments in etiology, anatomical characteristics,
      management and prognosis. PRDs can be particularly challenging, even for the most
      expert paediatric surgeons due to the higher prevalence of total retinal
      detachments, late diagnosis and bilateral involvement with respect to those which
      occur in adulthood. Moreover, the anatomical success, when achieved, is
      frequently not related to a functional recover. Postsurgical adverse events,
      refractive errors and amblyopia may additionally undermine the final outcome. Up
      to date there are few reviews regarding the approach of retinal detachment in
      children, mainly dealing with rhegmatogenous retinal detachment. In this review,
      rhegmatogenous, retinopathy of prematurity-related and Coats'-related PRDs were
      considered. The available literature from the last decades were reviewed and
      summarized. Epidemiology, etiology and clinical presentation, together with
      therapeutic approaches and outcomes have been reviewed and discussed.

PMID- 29062785
TI  - Posner-Schlossman syndrome induced laser in situ keratomileusis keratectasia-a
      case report.

PMID- 29062786
TI  - Above-average defocus curves in photopic and mesopic vision with multifocal
      intraocular lenses after laser assisted in situ keratomileusis.

PMID- 29062787
TI  - A long follow-up of a patient with bilateral retinoblastoma who underwent globe
      preserving therapy and had metastasis after 72mo.

PMID- 29062788
TI  - Intravitreal bevacizumab in treatment of retinal neovascularization from
      tuberculous retinal vasculitis.

PMID- 29062789
TI  - Mansonella ozzardi parasitic infestation in the orbit.

PMID- 29062790
TI  - How Can Personalized Medicine Improve Assisted Reproduction Technology Outcomes?

PMID- 29062792
TI  - Elevated Levels of Serum Vascular Endothelial Growth Factor-A Are Not Related to
      NK Cell Parameters in Recurrent IVF Failure.
AB  - BACKGROUND: Vascular Endothelial Growth Factor and NK cells have an interrelated
      role in angiogenesis that is critical for placentation and success of in vitro
      fertilization. An attempt was made to assess a possible relationship between the
      two in this study. METHODS: A case control study was performed comparing the
      serum levels of VEGF-A and its receptor VEGF-R1 with levels of NK cells,
      activated NK cells and NK cytotoxicity in 62 women with Repeated Implantation
      Failure (RIF). The healthy control group consisted of 72 women of similar age,
      without known issues in achieving pregnancy or evidence of autoimmunity. Levels
      of VEGF-A and VEGF-R1 were quantified by ELISA methods with standard curve
      interpolation. NK cell subsets were determined with flow cytometry using
      fluorescent-tagged anti-CD56, anti-CD16, anti-CD3 and anti-CD69. NK cytotoxicity
      was performed by incubating peripheral blood mononuclear cells and K562 cultured
      cells with propidium iodide, steroid, intralipid and intravenous immunoglobulin,
      using previously described methods. Statistical analysis involved Mann-Whitney-U
      and Spearman's rank correlation testing with p-values defined as <0.05. RESULTS:
      It was found that VEGF-A levels were significantly raised in women with RIF
      compared to healthy controls (362.9 vs. 171.6 pg/ml, p<0.0001), with no
      difference in VEGF-R1 levels between groups (1499 vs. 1202 pg/ml, p=0.4082).
      There was no correlation between VEGF-A or VEGF-R1 and the absolute levels of
      circulating NK cells, CD69 activated NK cells or NK cytotoxicity. CONCLUSION: The
      absence of correlation between VEGF-A or VEGF-R1 and NK cells suggests VEGF
      secretion and regulation is independent of NK cell activity in RIF.

PMID- 29062791
TI  - The Challenge of Human Spermatozoa Proteome: A Systematic Review.
AB  - Currently, there are 20,197 human protein-coding genes in the most expertly
      curated database (UniProtKB/Swiss-Pro). Big efforts have been made by the
      international consortium, the Chromosome-Centric Human Proteome Project (C-HPP)
      and independent researchers, to map human proteome. In brief, anno 2017 the human
      proteome was outlined. The male factor contributes to 50% of infertility in
      couples. However, there are limited human spermatozoa proteomic studies. Firstly,
      the development of the mapping of the human spermatozoa was analyzed. The human
      spermatozoa have been used as a model for missing proteins. It has been shown
      that human spermatozoa are excellent sources for finding missing proteins. Y
      chromosome proteome mapping is led by Iran. However, it seems that it is
      extremely challenging to map the human spermatozoa Y chromosome proteins based on
      current mass spectrometry-based proteomics technology. Post-translation
      modifications (PTMs) of human spermatozoa proteome are the most unexplored area
      and currently the exact role of PTMs in male infertility is unknown.
      Additionally, the clinical human spermatozoa proteomic analysis, anno 2017 was
      done in this study.

PMID- 29062793
TI  - Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the
      Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse
      Model.
AB  - BACKGROUND: Polycystic-ovary syndrome (PCOS) is a reproductive illness
      characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice,
      it was demonstrated that the oral administration of incremental dose of follicle
      stimulating hormone (FSH) attenuated some of PCOS characteristics. This work
      aimed to study the effect of ultra-low doses of combined FSH and progesterone
      orally administered on PCOS murine model. Moreover, the effect of sequential
      kinetic activation of administered hormones was tested. METHODS: Thirty-two
      female mice were used as animal model (four groups of eight animals each). Mice
      were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame
      oil. Control group received only oil. Simultaneously, each animal daily received
      per os an activated or a not-activated combination of FSH (0.44 pg) plus
      progesterone (0.44 pg) or saline solution as control. Serum testosterone,
      estradiol, progesterone and luteinizing hormone were analyzed as endocrine
      markers and a morphological study of antral follicle was conducted. Data were
      analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was
      considered significant. RESULTS: Dehyidroepiandrosterone treatment increased both
      estradiol and progesterone serum levels, besides testosterone, while reduced
      luteinizing hormone (p<0.05); histological examination revealed an increase of
      cystic follicles (p<0.05). Irrespective of activation, the combined FSH and
      progesterone treatments restored estradiol level (p>0.05 vs. control group) and
      reduced cystic signs in the follicles (p<0.05 vs. dehyidroepiandrosterone
      treatment). CONCLUSION: This study indicate that ultra-low doses of FSH and
      progesterone orally administrated can reduce the sternness of PCOS in the mouse
      model and open a route for the study of innovative approaches for PCOS treatment.

PMID- 29062794
TI  - Computational Analysis of High Risk Missense Variant in Human UTY Gene: A
      Candidate Gene of AZFa Sub-region.
AB  - BACKGROUND: The human Ubiquitously transcribed tetratricopeptide repeat gene, Y
      linked (UTY) gene encodes histone demethylase involved in protein-protein
      interactions. UTY protein evidence at protein level predicted intracellular and
      secreted protein. UTY is also involved in spermatogenesis process. METHODS: The
      high-risk non-synonymous single nucleotide polymorphism in the coding region of
      the UTY gene was screened by SNP database and identified missense variants were
      subjected to computational analysis to understand the effect on protein function,
      stability and structure by SIFT, PolyPhen 2, PANTHER, PROVEAN, I-Mutant 2, iPTREE
      STAB, ConSurf, ModPred, SPARKS-X, QMEAN, PROCHECK, project HOPE and STRING.
      RESULTS: A total of 151 nsSNPs variants were retrieved in UTY gene out of which
      one missense variant (E18D) was predicted to be damaging or deleterious using
      SIFT, PolyPhen 2, PANTHER and PROVEAN. Additionally, E18D variant showed less
      stability, high conservation and having role in post translation modification
      using i-Mutant 2 and iPTREE-STAB, ConSurf and ModPred, respectively. The
      predicted 3D model of UTY using SPARKS-X with z-score of 15.16 was generated and
      validated via QMEAN (Z-score of 0.472) and PROCHECK which plots Ramachandran plot
      (85.3% residues in most favored regions, 12.3% in additionally allowed regions,
      2.0% in generously allowed regions and 4.0% were in disallowed regions) and it
      indicates a good quality model. STRING showed that UTY interacts with ten
      different proteins. CONCLUSION: This study revealed that SNP data available on
      database was deduced to find out the most damaging nsSNPs i.e. rs3212293 (E18D).
      Therefore, it provides useful information about functional SNPs for future
      prospects concerning infertility in men.

PMID- 29062795
TI  - Y Chromosome Microdeletions in Infertile Men with Non-obstructive Azoospermia and
      Severe Oligozoospermia.
AB  - BACKGROUND: The purpose of the study was to investigate the frequencies and types
      of Y chromosome microdeletions in infertile men and to analyze the relationship
      between the levels of reproductive hormones and Y microdeletions. METHODS: A
      total of 1,226 infertile men were screened for Y chromosome microdeletions using
      multiplex PCR assay. Karyotype analysis was performed on peripheral blood
      lymphocytes with standard G-banding. Serum reproductive hormone levels were
      measured. RESULTS: Out of 1,226 infertile patients, 134 (10.93%) had Y
      microdeletions. One hundred seven of 765 (13.99%) non-obstructive azoospermic
      patients and 27 of 133 (20.30%) severe oligozoospermic patients had Y
      microdeletions. Among the 134 infertile men with Y microdeletions, the most
      frequent microdeletions were detected in the AZFc region, followed by AZFbc,
      AZFb, AZFa, AZFabc(Yq), Yp(SRY)+Yq, and partial AZFc regions. Karyotype analysis
      was available for 130 of the 134 patients with Y microdeletions. Of them, 36
      (27.69%) patients had sex chromosomal abnormalities. Levels of FSH and LH in
      patients with AZFc microdeletion were significantly lower, while those in
      patients with Yp(SRY)+Yq were significantly higher than in patients without Y
      microdeletions. Level of testosterone in patients with AZFabc(Yq) or Yp(SRY)+Yq
      was significantly lower than that in patients without Y microdeletions. However,
      there was no significant difference in the levels of reproductive hormones
      between all patients with and without Y microdeletions. CONCLUSION: These results
      highlight the need for Y chromosome microdeletion screening for correct diagnosis
      of male infertility. Obtaining reliable genetic information for assisted
      reproductive techniques can prevent unnecessary treatment and vertical
      transmission of genetic defects to offspring.

PMID- 29062796
TI  - Controlled Ovarian Hyperstimulation with Intrauterine Insemination Is More
      Successful After r-hCG Administration Than Spontaneous LH Surge.
AB  - BACKGROUND: The purpose of this study was to evaluate whether clinical pregnancy
      rate is affected by timing intrauterine insemination (IUI) according to serum LH
      surge, r-hCG trigger, or a combination of LH surge and r-hCG trigger in
      controlled ovarian hyperstimulation (COH) cycles for patients with a variety of
      infertility etiologies. METHODS: The last 365 consecutive COH-IUI cycles
      performed at ONE Fertility Burlington in 2014 were reviewed and categorized
      according to method of IUI timing. Associations between categorical variables
      were analyzed using a combination of Chi-square and Fisher's Exact tests, and
      between continuous variables using independent sample t-tests and logistic
      regression to a level of significance of p<0.05. RESULTS: The overall clinical
      pregnancy rate in this sample was 18.1% (66/365). Administration of r-hCG prior
      to IUI resulted in a higher clinical pregnancy rate compared with spontaneous
      serum LH surge: 18.2% vs. 5.8%, p=0.012. Patients in whom r-hCG was administered
      concomitantly with a serum LH surge had a higher clinical pregnancy than the r
      hCG trigger group (30.8% vs. 18.2%, p=0.004) and LH surge group (30.8% vs. 5.8%,
      p<0.001). A sub-group analysis revealed that patients receiving r-FSH, rather
      than clomiphene or letrozole, had a significantly higher clinical pregnancy rate
      after r-hCG trigger as compared to the LH surge group (21.7% vs. 2.1%, p=0.01).
      CONCLUSION: In subfertile couples undergoing COH-IUI, r-hCG administration was
      associated with an increased clinical pregnancy rate compared with spontaneous
      serum LH surge. When r-hCG was administered concomitantly with a serum LH surge,
      this benefit was amplified. The effect appears to be of particular importance in
      r-FSH-medicated cycles.

PMID- 29062797
TI  - Value of "Three Dimensional Multidetector CT Hysterosalpingography" in Infertile
      Patients with Non-Contributory Hysterosalpingography: A Prospective Study.
AB  - BACKGROUND: Infertility is a common health problem requiring imaging to delineate
      the anatomical causes in women. Three dimensional multi-detector computed
      tomography hysterosalpingography (3D-MDCT-HSG) offers an easy workup for uterine,
      tubal and peritoneal factors. METHODS: To present the spectrum of uterine, tubal
      and peritoneal factors on 3D-MDCT-HSG and determine its diagnostic accuracy for
      female factor infertility, a prospective study was conducted on 25 infertile
      women with non-diagnostic HSG from November 2012 to March 2014. Sixty four slice
      MDCT acquired the scan during pre-ovulatory phase by contrast instillation into
      uterine cavity. A blinded reviewer interpreted the 3D-MDCT-HSG and results were
      compared with final diagnosis made on hystero-laproscopy in 22 patients.
      Diagnostic accuracy of 3D-MDCT-HSG for various factors was expressed as
      sensitivity, specificity, positive and negative predictive value. RESULTS: MDCT
      HSG demonstrated definite findings in 96% of patients having non-diagnostic HSG.
      In this study, tubal, uterine and peritoneal abnormalities were present in
      68.75%, 56% and 32% of cases, respectively. 48 tubes in 25 patients were
      evaluated of which 22 tubes were blocked constituting the commonest finding
      present in 15 (60%) patients. The sensitivity, specificity, positive predictive
      value and negative predictive value for uterine factors was 83.33%, 100%, 100%
      and 96.84%, respectively, for tubal factors 93.55%, 94.68%, 85.29% and 96.83%,
      respectively and for peritoneal factors 62.5%, 92%, 71.43% and 88.46%,
      respectively. Mean effective radiation dose was 1.76+/-0.18 mSv in MDCT-HSG.
      CONCLUSION: 3D-MDCT-HSG can detect various factors responsible for female
      infertility especially tubal and uterine; in cases where HSG fails to clearly
      delineate the pathology.

PMID- 29062798
TI  - Pregnancy Luteoma in Ectopic Pregnancy: A Case Report.
AB  - BACKGROUND: Pregnancy luteoma is a rare non neoplastic condition of the ovary. It
      is usually asymptomatic and found incidentally during imaging in pregnancy or
      during cesarean section. Pregnancy luteoma can also occur after ectopic
      pregnancy. CASE PRESENTATION: A 30 year old female presented to G.B. Pant
      Hospital, Andaman and Nicobar Islands institute of Medical Sciences, Port Blair
      in October 2015 with abdominal pain. After initial investigations, exploratory
      laporotomy was done for ruptured ectopic pregnancy. Enlarged ovary was removed
      along with the ruptured portion of fallopian tube. Histopathological examination
      revealed solid aggregates of large cells with abundant eosinophilic cytoplasm;
      diagnosis of pregnancy luteoma was given. CONCLUSION: It must be considered in
      the differential diagnosis of ovarian masses in pregnant females that early
      diagnosis of this entity may avoid unnecessary radical surgery.

PMID- 29062799
TI  - Environmental Impact on Reproductive Health: Can Biomarkers Offer Any Help?

PMID- 29062800
TI  - Tiliacora triandra (Colebr.) Diels leaf extract enhances spatial learning and
      learning flexibility, and prevents dentate gyrus neuronal damage induced by
      cerebral ischemia/reperfusion injury in mice.
AB  - OBJECTIVE: The present study investigated the effects of a local Thai vegetable,
      Tiliacora triandra (Colebr.) Diels, also known as Yanang, against cerebral
      ischemia/reperfusion injury in mice. MATERIALS AND METHODS: Thirty male ICR mice
      were divided into three experimental groups of BLCCAO + 10% Tween 80, BLCCAO + T.
      triandra 300 mg/kg, and BLCCAO + T. triandra 600 mg/kg. Cerebral
      ischemia/reperfusion was induced by three minutes of bilateral common carotid
      artery occlusion (BLCCAO) followed by 18 days of reperfusion. Leaf extract was
      administered orally 24 hours after arterial occlusion and continued for 18
      consecutive days. Cognitive abilities were evaluated using the Morris water maze.
      Histological analysis was conducted in the dorsal hippocampus subregions CA1,
      CA3, and DG and white matter regions (the corpus callosum, internal capsule, and
      optic tract) using 0.1 % cresyl violet and 0.1% Luxol fast blue staining.
      RESULTS: Results showed that T. triandra leaf extract at the doses of 300 and 600
      mg/kg significantly enhanced spatial learning, and learning flexibility, and
      prevented neuronal death in the DG of mice following ischemia/reperfusion.
      CONCLUSION: T. triandra leaf extract enhanced spatial learning, and learning
      flexibility, and prevented DG neuronal death in a mice model of cerebral
      ischemia/reperfusion.

PMID- 29062801
TI  - Effects of ethanolic extract of Jasminum grandiflorum Linn. flowers on wound
      healing in diabetic Wistar albino rats.
AB  - OBJECTIVE: To evaluate wound healing activity of ethanolic extract of Jasminum
      grandiflorum Linn. (J. grandiflorum) flowers in diabetic rats. MATERIALS AND
      METHODS: Streptozotocin-induced diabetic Wistar albino rats were divided into six
      groups (n=6).Three groups - diabetic control, positive control (that received
      Glibenclamide) and treatment (that received J. grandiflorum Linn. Flower extract)
      were operated for excision wounds (EW). These groups were evaluated for wound
      contraction and re-epithelization. The other three groups were operated for
      incision wounds (IW) and dead space wounds (DW). Incision and dead space wounds
      were produced in the same rats. IWs were analyzed for wound breaking strength and
      the granulation tissues from DWs were analyzed for dry weight, hydroxyproline
      content, and histology. RESULTS: IWs and DWs showed significant improvement in
      wound breaking strength (265.8+/-10.4 vs 332.5+/-8.2; p<0.05), granulation tissue
      dry weight (26.1+/-0.6vs 40.4+/-0.3; p<0.01) and hydroxyproline content (19.3+/
      0.5 vs 32.6+/-0.8; p<0.01) in treatment group as compared to control group. Neo
      angiogenesis was also high in treatment group. Wound contraction was earlier (day
      14) in treatment group compared to diabetic control (day 20). No significant
      improvement was seen in re-epithelization in treatment group. CONCLUSION:
      Ethanolic extract of J. grandiflorum Linn. flowers increases granulation tissue
      formation as well as neo-angiogenesis. It also enhances wound contraction;
      however, re-epithelization was not significantly affected. J. grandiflorum Linn.
      flowers could be potentially effective in promotion of diabetic wounds healing by
      increasing granulation tissue formation and enhancing wound contraction; however,
      further studies are required for its clinical application.

PMID- 29062802
TI  - Modulation of lung inflammation and immune markers in asthmatic rats treated by
      Portulaca oleracea.
AB  - OBJECTIVE: Previous studies indicated anti-inflammatory effects for Portulaca
      oleracea in various inflammatory disorders. In this study, the effects of P.
      oleracea on bronchoalveolar lavage fluid (BALF) levels of total protein (TP),
      Phospholipase A2 (PLA2) and IgE in sensitized rats were examined. MATERIALS AND
      METHODS: Male rats were randomly divided into six groups namely, control (group
      C), sensitized rats (group S), sensitized animal treated with three
      concentrations of the extract of P. oleracea and dexamethasone (n = 8 for each
      group). The levels of TP, PLA2 and IgE in BALF were measured. RESULTS: The levels
      of TP, PLA2 and IgE were significantly increased in the BALF of group S compared
      to group C (p<0.001 for all cases). However, treatment of S rats with all
      concentrations of the extract, resulted in a significant and concentration
      dependent reduction in BALF levels of TP, PLA2 and IgE compared to group S
      (p<0.001 for all cases except for the effect of the low extract concentration on
      TP). Dexamethasone treatment also led to significant reduction of TP, PLA2 and
      IgE (p<0.001 for all cases). The effect of dexamethasone treatment on PLA2 was
      significantly higher than the effects of all extract concentrations (p<0.001 for
      all cases). However, the effect of high extract concentration on TP and IgE was
      significantly higher than that of dexamethasone (p<0.001 both cases). CONCLUSION:
      The results indicated anti-inflammatory and immunomodulatory effects of P.
      oleracea in sensitized rats (as an animal model of asthma) which was equal or
      more marked than dexamethasone at studied concentrations.

PMID- 29062803
TI  - The antioxidant activity of Beta vulgaris leaf extract in improving scopolamine
      induced spatial memory disorders in rats.
AB  - OBJECTIVE: Medicinal plants have attracted global attention due to their safety
      as well as their considerable antioxidant content that helps to prevent or
      ameliorate various disorders including memory impairments. This study was
      conducted to investigate the effect of beet root (Beta vulgaris) leaf extract on
      scopolamine-induced spatial memory impairments in male Wistar rats. MATERIALS AND
      METHODS: Male Wistar rats were randomly divided into 5 groups (n=10): Control
      (C), scopolamine 1 mg/kg/day (S), scopolamine+50 mg/kg B. vulgaris leaf extract
      (S+B 50), scopolamine+100 mg/kg B. vulgaris leaf extract (S+B 100) and
      scopolamine+200 mg/kg B. vulgaris leaf extract (S+B 200). Morris water maze task
      was used to assess spatial memory. Serum antioxidant capacity and malondialdehyde
      (MDA) level were also measured. RESULTS: Group S spent significantly less time in
      the target quadrant compared to the control group, and the administration of B.
      vulgaris leaf extract (100 and 200 mg/kg) significantly increased this time
      (p<0.05). Scopolamine decreased serum antioxidant capacity and increased serum
      MDA level yet insignificantly. B. vulgaris extract (200 mg/kg) significantly
      increased the antioxidant capacity and decreased serum MDA level in scopolamine
      treated rats (p<0.05). CONCLUSION: Our results suggested that B. vulgaris leaf
      extract could ameliorate the memory impairments and exhibited protective effects
      against scopolamine-induced oxidation. Further investigation is needed to isolate
      specific antioxidant compounds from B. vulgaris leaf extract with protective
      effect against brain and memory impairments.

PMID- 29062804
TI  - Effect of the methanolic extracts of different parts of Ferula assa-foetida on
      naloxone-induced withdrawal behavior in morphine-dependent mice.
AB  - OBJECTIVE: Ferula assa-foetida, a native species in Iran, is used for treatment
      of several diseases particularly for neurological disorders in Iranian
      Traditional Medicine. The aim of this study is to investigate the effect of
      methanolic roots, fruits, and aerial parts extracts of Ferula assa-foetida on
      withdrawal syndrome in morphine-dependent mice. MATERIALS AND METHODS: Aerial
      parts, roots, and fruits of the plant were separately extracted with 80% MeOH.
      For induction of dependence, morphine (50, 50 and 75 mg/kg) was injected
      subcutaneously three times daily (10 am, 1 pm and 4 pm) for three days and a last
      dose of morphine (50 mg/kg) was administrated on the fourth day. Withdrawal
      syndrome was induced by injection of naloxone (5 mg/kg, intraperitoneal) 2 hr
      after the final dose of morphine. Different doses of the extracts were
      administered i.p. 60 minutes before naloxone injection and withdrawal sign was
      recorded 2 minutes after naloxone injection for a period of 60 minutes. RESULTS:
      Pre-treatment of animals with different doses (2.5, 5, 10, 20 mg/kg) of
      methanolic extract of the aerial parts of F. assa-foetida caused a significant
      decrease in naloxone-induced behavior. Intraperitoneal administration of
      different doses (10, 15, 20, 25 mg/kg) of methanolic extract of the fruit
      significantly reduced the naloxone-induced withdrawal behavior (p<0.001).
      CONCLUSION: It might be concluded that the extracts of Ferula assa-foetida affect
      morphine withdrawal syndrome possibly via interference with the neurotransmitters
      in nervous system.

PMID- 29062805
TI  - Evaluation of the effect of soybean diet on interferon-alpha-induced depression
      in male mice.
AB  - OBJECTIVE: Interferon-alpha (IFN) therapy can cause depressive symptom which may
      lead to drug discontinuation. By interfering with tryptophan pathway, the
      available level of tryptophan required for serotonin synthesis decreases which
      could be related to depression. The aim of this study was to evaluate whether
      soybean diet could improve IFN-induced depression. MATERIALS AND METHODS: Male
      mice weighing 28+/-3 g were used in the forced swimming test (FST) as an animal
      model of depression; also, locomotor activity was recorded. IFN 16*105 IU/kg was
      injected subcutaneously for 6 days. Animals were fed with regular diet or soybean
      diet at 3 concentrations throughout the experiment. Fluoxetine was the reference
      drug. To check whether the tryptophan content in the soy bean diet was effective,
      a group of animals was injected with a single dose of tryptophan on the test day.
      RESULTS: IFN-alpha increased the immobility time in the FST (192 sec +/- 5.4),
      that denotes depression in mice. Soybean diets caused less immobility that was
      more profound with 50% soybean (26.4 sec +/- 6). This diet overcame the
      depression caused by IFN in the FST (54 sec+/-18). This result was parallel with
      that of tryptophan injected to animals (38 sec+/-17). All the animals showed
      normal locomotor activity. CONCLUSION: For the first time, we showed that soybean
      diet could counteract with depression caused by IFN-alpha. Since tryptophan
      therapy had similar effects, possibly the tryptophan content of soybean had
      induced the serotonin synthesis. Thus, not only less harmful kynurenine was
      produced but also more serotonin was available in the brain to overcome
      depression. However, this interpretation needs further evaluations.

PMID- 29062806
TI  - A simple, sensitive and rapid isocratic reversed-phase high-performance liquid
      chromatography method for determination and stability study of curcumin in
      pharmaceutical samples.
AB  - OBJECTIVE: This study was designed to develop and validate a new reversed-phase
      high-performance liquid chromatography (RP-HPLC) method based on Q2 (R1)
      International Conference on Harmonization (ICH) guideline for determination of
      curcumin in pharmaceutical samples. MATERIALS AND METHODS: The HPLC instrument
      method was optimized with isocratic elution with acetonitrile: ammonium acetate
      (45:55, v/v, pH 3.5), C18 column (150 mm*4.6 mm*5 um particle size) and a flow
      rate of 1 ml/min in ambient condition and total retention time of 17 min. The
      volume of injection was set at 20 ul and detection was recorded at 425 nm. The
      robustness of the method was examined by changing the mobile phase composition,
      mobile phase pH, and flow rate. RESULTS: The method was validated with respect to
      precision, accuracy and linearity in a concentration range of 2-100 ug/ml. The
      limit of detection (LOD) and limit of quantification (LOQ) were 0.25 and 0.5
      ug/ml, respectively. The percentage of recovery was 98.9 to 100.5 with relative
      standard deviation (RSD) < 0.638%. CONCLUSION: The method was found to be simple,
      sensitive and rapid for determination of curcumin in pharmaceutical samples and
      had enough sensitivity to detect degradation product of curcumin produced under
      photolysis and hydrolysis stress condition.

PMID- 29062807
TI  - Evaluation of the effects of the hydroalcoholic extract of Terminalia chebula
      fruits on diazinon-induced liver toxicity and oxidative stress in rats.
AB  - OBJECTIVE: Diazinon causes oxidative stress and dysfunction of the liver. This
      study was undertaken to evaluate the effects of the hydroalcoholic extract of
      Terminalia chebula, on some biochemical and histopathological parameters of liver
      tissue in diazinon-administered rats. MATERIALS AND METHODS: Wistar rats were
      orally administered with 25 mg/kg body weight diazinon. Vehicle (distilled water)
      and silymarin (50 mg/kg body weight) were used as the negative and positive
      control groups, respectively. Diazinon-administered groups were treated with
      T.chebula (Terminalia chebula) fruit extract (200, 400, and 800 mg/kg). After 15
      days of treatment, the blood specimens and liver samples were examined. RESULTS:
      In diazinon-treated group, the levels of serum urea, high density lipoprotein
      (HDL), and liver superoxide dismutase (SOD), catalase (CAT), and vitamin C
      significantly decreased (p<0.05) compared to control. Also, in this group, serum
      triglyceride (TG), total cholesterol (TC), very low density lipoprotein
      cholesterol (VLDL), protein carbonyl (PC), malondialdehyde, tumor necrosis factor
      alpha (TNF-alpha), and TNF-alpha gene expression significantly increased (p<0.05)
      as compared to the control (vehicle-treated rats). Treatment with T. chebula
      resulted in a significant increase (p<0.05) in CAT, SOD, vitamin C, HDL and a
      significant decrease (p<0.05) in the level of urea, MDA, PC, TG, TC, VLDL, TNF
      alpha protein, and the gene expression of TNF-alpha compared with test without
      treatment group. Histopathological evidence demonstrated that treatment with T.
      chebula extract could decrease liver lymphocyte infiltration. CONCLUSION: The
      present study suggests that T. chebula fruit extract has protective effects
      against diazinon-induced oxidative stress.

PMID- 29062808
TI  - Acute effects of thermally processed pili (Canarium ovatum, Engl.) pomace drink
      on plasma antioxidant and polyphenol status in humans.
AB  - OBJECTIVE: Pili (Canarium ovatum, Engl.) pomace is an underutilized agricultural
      waste that possesses great potential to be regarded as a functional food
      ingredient. The aim of this study was to measure the polyphenol content and
      antioxidant activity of pili pomace drink and determine the influence of heating
      on these parameters. Moreover, it sought to assess the acute effects of thermally
      processed pili pomace drink on plasma antioxidant and polyphenol status in
      humans. MATERIAL AND METHODS: Ten healthy adults received a single dose (130 ml)
      of pili pomace drink following an overnight fasting, and blood was collected at
      0, 30, 60, 120 and 240 min after ingestion of pili pomace. Plasma total
      polyphenol content was measured using Folin-Ciocalteu method, while total
      antioxidant capacity (TAC) was determined using ferric reducing antioxidant power
      (FRAP) assay in uricase-treated and untreated plasma samples. RESULTS:
      Significant changes in plasma antioxidant and polyphenol levels were observed,
      reaching maximum levels at 120 and between 30 - 60 min, respectively (p<0.05).
      Both plasma polyphenols and TAC remained significantly above baseline values
      throughout the entire test period (p<0.05). CONCLUSION: Results raised the
      possibility that an acute consumption of this phenolic-rich pili pomace drink may
      enhance plasma antioxidant and polyphenol status in humans. Future studies on
      other unidentified metabolites from pili pomace that may have enhanced the
      antioxidant activity of plasma should be done.

PMID- 29062809
TI  - Parenchymal Infiltration in Primary Diffuse Leptomeningeal Gliomatosis: Dynamic
      Changes in Brain MRI.
AB  - Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare and fatal disease
      with no special clinical manifestations. Here, we report the dynamic brain
      magnetic resonance imaging (MRI) changes in a 30-year-old female PDLG patient
      over a 10-month period. MRI showed aggressive dilation of the subarachnoid space
      and the ventricular system, numerous encapsulated cysts in the subarachnoid space
      and the dilated cerebral sulci, diffuse reticulated or focal nodular enhancement
      in the subarachnoid space, as well as overall enhancement in the cystic walls. In
      addition to the aforementioned PDLG pathological findings, MRI also revealed non
      contrasted solid lesions and a contrasted cyst-like lesion in the paraventricular
      areas. The dynamic and multiform neuroradiological changes help us to understand
      the pathological process of PDLG. Of particular interest is the discovery that
      parenchymal infiltration can occur in PDLG.

PMID- 29062812
TI  - Educate is one of our missions.

PMID- 29062811
TI  - Activation of NF-kB-Mediated TNF-Induced Antimicrobial Immunity Is Required for
      the Efficient Brucella abortus Clearance in RAW 264.7 Cells.
AB  - In this study, we explore the regulatory roles of pro-inflammatory cytokine tumor
      necrosis factor alpha (TNF) in the innate immunity of macrophages against B.
      abortus infection. We show that infection of macrophage with B. abortus induces
      marked expression and secretion of TNF which subsequently binds to TNF receptor 1
      (TNFR-1) and activates a downstream signaling cascade of the innate immunity.
      Blocking of TNF signaling resulted in a notable increase of B. abortus survival
      which was associated with an increase of anti-inflammatory cytokine interleukin
      10 (IL-10), a beneficial effector of Brucella survival, as well as remarkable
      decrease of reactive oxygen species (ROS) and nitric oxide (NO), antibrucella
      molecules. However, surprisingly, the interference of TNF did not show any
      influence on phagolysosome and cell death events. Furthermore, the
      transcriptional factor NF-kB was found to be a main mediator of TNF signaling
      when blocking of NF-kB pathway drastically suppressed the TNF-induced
      brucellacidal effect. Taken together, these findings clearly indicate that the
      immune cascade activated by TNF/TNFR-1 is required for the sufficient resistance
      to B. abortus survival in macrophages.

PMID- 29062813
TI  - Traumatic anterior instability of the shoulder.
AB  - The shoulder is the most unstable joint in the human body. Traumatic anterior
      instability of the shoulder is a common condition, which, especially in young
      patients, is associated with high recurrence rates. The effectiveness of non
      surgical treatments when compared to surgical ones is still controversial. The
      purpose of this study was to review the literature for current concepts and
      updates regarding the treatment of this condition.

PMID- 29062810
TI  - A Trickster in Disguise: Hyaluronan's Ambivalent Roles in the Matrix.
AB  - Hyaluronan (HA) is a simple but diverse glycosaminoglycan. It plays a major role
      in aging, cellular senescence, cancer, and tissue homeostasis. In which way HA
      affects the surrounding tissues greatly depends on the molecular weight of HA.
      Whereas high molecular weight HA is associated with homeostasis and protective
      effects, HA fragments tend to be linked to the pathologic state. Furthermore, the
      interaction of HA with its binding partners, the hyaladherins, such as CD44, is
      essential for sustaining tissue integrity and is likewise related to cancer. The
      naked mole rat, a rodent species, possesses a special form of very high molecular
      weight (vHMW) HA, which is associated with the extraordinary cancer resistance
      and longevity of those animals. This review addresses HA and its diverse facets:
      from HA synthesis to degradation, from oligomeric HA to vHMW-HA and from its
      beneficial properties to the involvement in pathologies. We further discuss the
      functions of HA in the naked mole rat and compare them to human conditions.
      Though intensively researched, this simple polymer bears some secrets that may
      hold the key for a better understanding of cellular processes and the development
      of diseases, such as cancer.

PMID- 29062815
TI  - A comparison study of radiographic and computerized tomographic angles in slipped
      capital femoral epiphysis.
AB  - OBJECTIVE: To compare proximal femur radiologic angles in patients with slipped
      capital femoral epiphysis and to analyze whether computerized tomography may
      modify the treatment. METHODS: Cross-sectional study comparing and analyzing the
      similarity between angles and radiologic classification of interest in slipped
      capital femoral epiphysis (SCFE). RESULTS: It was observed that the therapeutic
      management in slipped capital femoral epiphysis might be modified depending on
      the classification and radiologic acquisition method adopted. CONCLUSION:
      Multiplanar assessment of proximal femoral deformity in patients with slipped
      capital femoral epiphysis is a viable option, with the potential to modify the
      disease classification and, consequently, the therapeutic management.

PMID- 29062816
TI  - Fat embolism syndrome in femoral shaft fractures: does the initial treatment make
      a difference?
AB  - OBJECTIVE: To identify the risk factors correlated with the initial treatment
      performed. METHODS: This is a retrospective study involving a total of 272
      patients diagnosed with femoral shaft fractures. Of the patients, 14% were kept
      at rest until the surgical treatment, 52% underwent external fixation, 10%
      received immediate definitive treatment, and 23% remained in skeletal traction
      (23%) until definitive treatment. RESULTS: There were six cases of fat embolism
      syndrome (FES), which showed that polytrauma is the main risk factor for its
      development and that initial therapy was not important. CONCLUSION: Polytrauma
      patients have a greater chance of developing FES and there was no influence from
      the initial treatment.

PMID- 29062814
TI  - Total hip arthroplasty: a still evolving technique.
AB  - It has been advocated that total hip arthroplasty (THA) is probably the most
      successful surgical intervention performed in Medicine. In the 1960s, Sir John
      Charnley not only introduced, but also modified and improved the technique of
      cemented arthroplasties. The concepts on biological fixation established by
      Pillar and Galante served as the foundation for the development of uncemented
      implants that are now used worldwide. Currently, THA is a worldwide widespread
      surgery performed on millions of people. However, keeping abreast of the large
      number of information available on these procedures, especially on implant
      fixation, designs, different tribological pairings, and the long-term results can
      be challenging at times. This article is a brief update on the main aspects of
      THA.

PMID- 29062817
TI  - Primary and secondary osteoporotic fractures prophylaxis: evaluation of a
      prospective cohort.
AB  - OBJECTIVE: To measure the prevalence of primary drug prevention of fractures due
      to osteoporosis in patients admitted to a tertiary teaching hospital, in a medium
      sized city, admitted with osteoporotic fractures. Moreover, to identify the
      incidence of prescribing secondary prophylaxis after the first fracture event. At
      the same time, the prevalence of risk factors for such fractures as described in
      the literature was measured. METHODS: This longitudinal prospective study was
      based on a cohort of patients admitted in a tertiary teaching hospital from
      October 2015 to January 2016. Patients with low energy or fragility fractures
      were included in the study regardless of gender or race, over the age of 50
      years. All patients who did not have these characteristics were excluded. The
      follow-up lasted four months. Serial questionnaires were applied at admission and
      in the follow-up consultations at four to eight weeks and at 16 weeks. RESULTS:
      Only one patient reported receiving treatment with specific drugs for the disease
      before hospital admission, resulting in a prevalence of primary chemoprophylaxis
      of only 2.27%. No patient was prescribed medication for the treatment of
      osteoporosis after the fracture. The prevalence of risk factors was similar to
      those found in the literature review. CONCLUSION: In the present study, the
      frequency of primary and secondary osteoporosis chemoprophylaxis in patients who
      were admitted with fragility fractures was low, as well as the early indication
      of drug treatment after the first fracture. The prevalence of fragility fracture
      risk factors is similar to those reported in the literature.

PMID- 29062818
TI  - Infection rate in adult patients with open fractures treated at the emergency
      hospital and at the ULBRA university hospital in Canoas, Rio Grande do Sul,
      Brazil.
AB  - OBJECTIVE: To identify the infection rate in adult patients with open fractures
      treated at two tertiary hospitals in the city of Canoas, Rio Grande do Sul,
      Brazil. METHODS: This quantitative descriptive study was conducted at Hospital de
      Pronto Socorro de Canoas. Eligible participants were adults aged 18-60 years with
      open fractures who were admitted to the orthopedic trauma service from January to
      May 2014 and followed-up for one year. RESULTS: A total of 133 patients with open
      fractures were included; most were men (92.48%), with a mean age of 36 years.
      There was a predominance of Gustilo-Anderson type III fractures. The infection
      rate was 18.80%, being more frequent in Gustilo-Anderson type III fractures
      (72.00%). The most commonly observed bacteria were Staphylococcus aureus and
      Enterobacter aerogenes. CONCLUSION: The infection rate in open fractures of
      patients initially treated at the emergency department of HPSC was 18.8%. The
      infections occurred predominantly in Gustilo-Anderson type III fractures. The
      bacteria with the highest incidence in infections were Staphylococcus aureus and
      Enterobacter aerogenes.

PMID- 29062819
TI  - Conventional plate and screws in medial opening-wedge high tibial osteotomy: are
      they sufficiently stable? A retrospective study.
AB  - OBJECTIVE: Opening-wedge osteotomy of the proximal tibia is a widely performed
      procedure for treating medial gonarthrosis in active patients and in the presence
      of varus malalignment of the lower limb. The fixation method is controversial,
      and the use of conventional implants has been abandoned in favor of implants with
      more modern locking screws. The aim of the present clinical study was to assess
      the maintenance of the correction achieved in cases wherein fixation was
      performed using conventional implants. METHODS: This retrospective study included
      51 patients who underwent opening-wedge high tibial osteotomy wherein fixation
      was performed using conventional implants (4.5-mm DCP plate and non-locking
      screws). Radiological findings regarding patellar height, tibial slope, and varus
      correction postoperatively and after consolidation were analyzed to assess the
      maintenance of the correction achieved by osteotomy. RESULTS: The mean loss of
      correction angle, calculated by the difference between the correction angle in
      the immediate postoperative period and that after consolidation, was 0.92 degrees
      +/- 0.9 degrees . In addition, changes in patellar height determined by the
      Blackburne-Peel method and in the sagittal slope of the tibial plateau were not
      significant or clinically relevant. CONCLUSIONS: The use of conventional plates
      and screws is viable in the fixation of opening-wedge high tibial osteotomy
      because they provide enough stability to maintain the achieved correction until
      consolidation, without significant changes.

PMID- 29062820
TI  - Comparison of Puddu osteotomy with or without autologous bone grafting: a
      prospective clinical trial.
AB  - OBJECTIVES: To test the hypothesis that autologous iliac bone grafts do not
      enhance clinical results and do not decrease complication rates in patients
      undergoing medial opening-wedge high tibial osteotomy. METHODS: Forty patients
      allocated in a randomized, two-armed, double-blinded clinical trial were
      evaluated between 2007 and 2010. One group received bone graft, and the other
      group was left without filling the osteotomy defect. The primary outcome was the
      Knee Society Score. Radiographic measurement of the frontal anatomical femoral
      tibial angle and the progression of osteoarthritis according to the modified
      Ahlback classification were used as secondary outcomes. RESULTS: There was no
      difference in KSS scale between the graft group (64.4 +/- 21.8) and the graftless
      group (61.6 +/- 17.3; p = 0.309). There was no difference of angle between the
      femur and tibia in the frontal plane between the groups (graft = 184 +/- 4.6
      degrees, graftless = 183.4 +/- 5.1 degrees; p = 1.0), indicating that there is no
      loss of correction due to the lack of the graft. There was significant
      aggravation of osteoarthritis in a greater number of patients in a graft group (p
      = 0.005). CONCLUSION: Autologous iliac bone graft does not improve clinical
      outcomes in medium and long-term follow-up of medial opening-wedge high tibial
      osteotomy fixed with a first generation Puddu plate in the conditions of this
      study.

PMID- 29062821
TI  - Outcome assessment in the treatment of rotator cuff tear: what is utilized in
      Brazil?
AB  - This review evaluated the outcomes used in clinical studies involving rotator
      cuff tear published in the last decade in the two leading Brazilian orthopedic
      journals. A literature review was performed using the journals Revista Brasileira
      de Ortopedia and Acta Ortopedica Brasileira. It included all original clinical
      articles describing at least one outcome measured before or after any clinical or
      surgical intervention related to rotator cuff tear, published between 2006 and
      2015. The authors evaluated range of motion, muscle strength, patient
      satisfaction, and tendon integrity and functional outcomes scores. There were 25
      clinical studies published about rotator cuff in the two principal Brazilian
      orthopedic journals in the last decade, 20 case series (80%), one case-control
      (4%), and four cohorts (16%). Objective measures such as muscle strength, patient
      satisfaction, and evaluation of tendon integrity were little used. Range of
      motion measurements were performed in 52% of the articles. Evaluations of muscle
      strength and patient satisfaction were reported by 28% and 16% of the studies,
      respectively. Only 28% of the articles evaluated tendon integrity after surgery.
      Of these, 16% did so by magnetic resonance imaging and 12% by ultrasonography.
      The most used scale was the UCLA, present in 92% of the articles, while the
      Constant-Murley appeared in 20%. Scales deemed reliable, with high internal
      consistency and good responsiveness, were rarely used.

PMID- 29062822
TI  - Stand-alone anterior lumbar interbody fusion - complications and perioperative
      results.
AB  - OBJECTIVES: Historically, anterior lumbar interbody fusion (ALIF) was related to
      high rates of intraoperative complications and adverse events related to
      interbody devices. In recent decades, there have been technical adjustments, and
      cages that are more suitable have emerged. The aim of this study is to evaluate
      the efficacy and complication rate of the use of stand-alone mini-ALIF using a
      self-locking cage. METHODS: Retrospective single center study. Inclusion
      criteria: retroperitoneal mini-ALIF for single-level fusion (L5S1); self-locking
      cage; DDD/stenosis and grade I spondylolisthesis. Exclusion criteria: posterior
      supplementation, previous fusion/arthroplasty. Endpoints: surgery data,
      intraoperative and perioperative adverse events related both to surgical access
      and to the intersomatic device. RESULTS: Eighty-seven cases were enrolled. Median
      surgical time was 90 min; median blood loss was 100 mL. The median length of stay
      in the ICU was zero days; median hospital stay was one day. Ten cases had an
      adverse event (11.5%): four major adverse events (4.6%; 3 L bleeding; DVT;
      retroperitoneal haematoma; incisional hernia), and seven minor events (8%;
      peritoneum injury; minor vascular injury; events related to the cage). No cases
      of retrograde ejaculation were observed. There was improvement in pain, physical
      restriction, and quality of life (p < 0.001). CONCLUSIONS: The mini-ALIF
      procedure performed for single-level fusion at the distal lumbar level
      demonstrated low adverse event rates related to both the surgical approach and to
      the intersomatic device, with reduced hospital stay and satisfactory
      perioperative clinical results.

PMID- 29062823
TI  - Interaction of demographic factors with the results of the surgery for
      degenerative disease of the cervical spine: a retrospective evaluation.
AB  - OBJECTIVE: Degenerative disease of the cervical spine is a frequent source of
      intermittent neck pain, where the predominant symptom is axial neck pain. The
      indications for surgical treatment are reserved for the cases where the
      conservative treatment has not relieved the symptoms or the patient presents
      progressive neurological impairment. The objective of this study was to evaluate
      the prognostic factors involved in patients submitted to surgical treatment of
      the cervical spine. METHODS: The study analyzed data from patients submitted to
      cervical spine surgery between July 2011 and November 2015 (n = 58). The
      evaluated data included smoking habits, hypertension, diabetes, overweight,
      surgical technique, and number of levels of fusion. The primary outcome was
      defined as pain and the secondary outcomes were quality of life and disability.
      RESULTS: A statistically significant difference was found between baseline and
      the 12-month post-operative results regarding pain in favor of non-hypertensive
      patients (p = 0.009) and discectomy plus instrumentation (p = 0.004). There was
      also significant difference between the results of neck disability in favor of
      non-hypertensive patients (p = 0.028) and patients with body mass index lower
      than 25 kg/m2 (p = 0.005). There was no significant interaction between any
      analyzed data and the quality of life score results. CONCLUSIONS: Non
      hypertensive patients, those with body mass index lower than 25 kg/m2, and those
      submitted to discectomy combined with arthrodesis of the cervical spine are the
      most benefited by cervical degenerative disease surgery.

PMID- 29062824
TI  - Comparative study of topical vs. intravenous tranexamic acid regarding blood loss
      in total knee arthroplasty.
AB  - OBJECTIVE: To compare topical vs. intravenous tranexamic acid (TA) in total knee
      arthroplasty regarding blood loss and transfusion. METHODS: Ninety patients were
      randomized to receive TA intravenously (20 mg/kg in 100 mL of saline; group IV),
      topically (1.5 g in 50 mL of saline, sprayed over the operated site, before
      release of the tourniquet; topical group), or intravenous saline (100 mL with
      anesthesia; control group). The volume of drained blood in 48 h, the amount of
      transfused blood, and the serum levels of hemoglobin and hematocrit before and
      after surgery were evaluated. RESULTS: The groups were similar for gender, age,
      weight, laterality, and preoperative hemoglobin and hematocrit levels (p > 0.2).
      The hemoglobin level dropped in all groups when comparing the preoperative and
      the 48-h evaluations: the control group decreased 3.8 mg/dL on average, while the
      IV group had a decrease of 3.0, and the topical group, of 3.2 (p = 0.019). The
      difference between the control and IV groups was confirmed by Bonferroni test (p
      = 0.020). The difference between the control group and the topical group was not
      significant (p = 0.130), although there was less reduction in hemoglobin in the
      topical group; the comparison between the IV group and the topical group was also
      not significant (p = 1.000). CONCLUSION: Using topic and IV tranexamic acid
      decreased blood loss and the need for transfusion in total knee arthroplasty.
      Topical application showed results similar to IV use regarding the need for blood
      transfusion, but without the possible side effects of IV administration.

PMID- 29062825
TI  - Relationship of age and type of obstetric brachial plexus paralysis in forearm
      pronosupination.
AB  - OBJECTIVE: To evaluate the arc of forearm pronosupination of patients with
      sequelae of birth paralysis and correlate with these variables. METHODS: 32
      children aged between 4 and 14 years with total or partial lesions of the
      brachial plexus were evaluated; measurements of pronation and supination, active
      and passive, were made, both on the injured side and the unaffected side.
      RESULTS: A statistically significant difference was observed between the injured
      side and the normal side, but there was no difference between the groups
      regarding age or type of injury. CONCLUSION: The age and type of injury did not
      impact on the limitation of the forearm pronosupination in children with sequelae
      of birth paralysis.

PMID- 29062827
TI  - Metacarpal stress fracture in amateur tennis player - an uncommon fracture.
AB  - Most stress fractures occur in the lower limbs and are rarely observed in the
      upper limbs. The second metacarpal is the longest of all the metacarpals and has
      the largest base, articulating with the trapezium, trapezoid, capitate, and third
      metacarpal. In athletes, stress fractures in non-weight bearing joints are
      uncommon. Therefore, the shaft of the second metacarpal bone undergoes a higher
      load - the maximum tension at the base of the second metacarpal is amplified when
      the hand grasps a tool such as a tennis racquet.

PMID- 29062828
TI  - Giant palmar lipoma - an unusual cause of carpal tunnel syndrome.
AB  - Lipoma is a quite common type of soft-tissue tumor, but it is rarely found in the
      hand. Hand lipomas are generally asymptomatic; however, when they become too
      large or when they are present in some specific location, they can cause symptoms
      due to compression of the median nerve. These tumors must be correctly
      characterized preoperatively with imaging exams and the proper management is the
      complete removal of the tumor and release of the median nerve. The authors
      present the case of a female patient with carpal tunnel syndrome due to
      compression of the median nerve by a giant palmar lipoma, successfully treated
      with tumor excision and nerve release.

PMID- 29062826
TI  - Ultrasound evaluation of the rotator cuff after osteosynthesis of proximal
      humeral fractures with locking intramedullary nail.
AB  - OBJECTIVE: To evaluate supraspinatus tendon integrity with ultrasound (US) in
      patients submitted to proximal humeral fracture (PHF) fixation with a locking
      intramedullary nail. METHODS: Thirty-one patients with PHF treated with
      curvilinear locking intramedullary nail, aged between 50 and 85 years, were
      assessed by US at six months postoperatively and clinically at six and 12 months
      postoperatively. The primary aim was supraspinatus tendon integrity, evaluated by
      US at six months postoperatively. Secondary aims included the Constant-Murley,
      DASH score, and visual analog pain scores, as well as complications and
      reoperation rates. RESULTS: Full-thickness rotator cuff ruptures were observed in
      four patients (13%), supraspinatus ruptures in three cases (10%), and
      subscapularis ruptures in one case (3%). Partial ruptures were diagnosed in 10
      cases (32%). The results using the Constant-Murley score at 12 months were 71.3
      +/- 15.2 points for the entire series, with 73.2 +/- 16.1 points for patients
      without rotator cuff ruptures and 68.7 +/- 14.1 points for those with partial or
      complete ruptures, without a statistically significant difference (p = 0.336).
      Complications, exclusively for rotator cuff ruptures, were observed in nine
      patients (29%). CONCLUSION: A high rate of rotator cuff ruptures was
      demonstrated, with partial ruptures in 32% of cases and full-thickness ruptures
      in 13%. However, clinical results are satisfactory, and are not influenced by the
      presence of rotator cuff ruptures.

PMID- 29062829
TI  - Total knee replacement in patients with diffuse villonodular synovitis.
AB  - This paper reports a case of diffuse pigmented villonodular synovitis (DPVNS),
      associated with advanced gonarthrosis, submitted to total knee replacement. The
      patient had progressive pain and swelling. She had two previous surgeries,
      firstly arthroscopic synovectomy and subsequently open synovectomy associated
      with radiotherapy, with recurrence of the disease. Magnetic resonance imaging
      revealed diffuse synovitis, advanced arthrosis, and bone cysts. The patient was
      submitted to a total knee replacement and synovectomy. There was a good
      postoperative clinical course, with improvement of pain, function, and joint
      edema on examination. The patient will be followed regarding the possibility of
      disease recurrence and implant survival.

PMID- 29062830
TI  - Dynamic ulnar impaction syndrome in tennis players: report of two cases.
AB  - In this report, two tennis players with symptoms of ulnar impaction syndrome are
      reviewed. Both players have neutral ulnar variance. These cases represent dynamic
      ulnar impaction syndrome, when the impact between ulna and carpus occurs during
      conditions of pronated grip. The literature and the treatment of these two cases
      are discussed.

PMID- 29062831
TI  - Chronic recurrent multifocal osteomyelitis: a case report.
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic
      inflammatory disease that affects mainly children and young adults. The clinical
      signs and symptoms are nonspecific, hindering and delaying diagnosis.
      Radiological and histopathological tests are essential for its definition. A case
      of CRMO is reported, demonstrating the importance of clinical, laboratory, and
      radiological data for diagnosis.

PMID- 29062832
TI  - Mucinous Cystadenoma: A Rare Hepatic Tumor in a Child.
AB  - Mucinous cystadenomas (MCAs) of the liver (also called hepatic biliary
      cystadenomas) are rare tumors that comprise about 5% of cystic masses of the
      liver in adults. These slow-growing lesions most commonly occur in middle-aged
      individuals, with a female sex predominance. Herein, we present a MCA in a 6-year
      old male, one of only very few such cases described in the pediatric literature
      to date. Although MCAs are generally considered benign lesions, malignant
      transformation rarely occurs. The recurrence rate is high when partial cyst
      excision is performed. Therefore, complete surgical cyst resection with clinical
      follow-up, including imaging, is warranted.

PMID- 29062833
TI  - A Comparative Study on Outcome of Government and Co-Operative Community-Based
      Health Insurance in Nepal.
AB  - BACKGROUND: There are different models for community-based health insurance
      (CBHI), and in Nepal, among them, the government and the local communities (co
      ops) are responsible for operating the CBHI models that are in practice. AIMS:
      The aim of this study is to compare the outcomes in relation to benefit packages,
      population coverage, inclusiveness, healthcare utilization, and promptness of
      treatment for the two types of CBHI models in Nepal. METHODS: This study was an
      observational and interactive descriptive study using the concurrent mixed
      approach of data collection, framing, and compilation. Quantitative data were
      collected from records, and qualitative data were collected from key informants
      in all 12 CBHI groups. Unstructured questionnaires, observation checklists, and
      memo notepads were used for data collection. Descriptive statistics and the Mann
      Whitney U test were used when appropriate. Ethically, written informed consent
      was obtained from the respondents who participated in the study, and they were
      told that they could withdraw from the study anytime. RESULTS: The study revealed
      the following: new enrolment did not increase in either group; however, the
      healthcare utilization rate did (Government 107% and co-ops 137%), while the
      benefit packages remained almost same for both groups. Overall, inclusiveness was
      higher for the government group. For the CBHI co-ops, enrollment among the
      religious minority and the discount negotiated with the hospitals for treatment
      were significantly higher, and the promptness in reaching a hospital was
      significantly faster (p < 0.05) than that in the government-operated CBHI.
      CONCLUSION: Findings indicate that CBHI through co-ops would be a better model
      because of its lower costs and ability to enhance self-responsiveness and the
      overall health system. Health insurance coverage is the most important component
      to achieve universal health coverage.

PMID- 29062834
TI  - Micropropagation and Subsequent Enrichment of Carotenoids, Fatty Acids, and
      Tocopherol Contents in Sedum dasyphyllum L.
AB  - A promising micropropagation protocol has been systematically established and
      demonstrated for the enhanced production of carotenoids, tocopherol and fatty
      acids in shoot tissues of Sedum dasyphyllum. Shoot tip explants were grown on
      Murashige and Skoog (MS) medium. Different concentrations of N6-benzyladenine
      (BA) or thidiazuron (TDZ) alone or in combination with alpha-naphthaleneacetic
      acid (NAA) were tested in order to stimulate multiple shoot production. Ideal
      shoot induction (100%) and maximized shoot numbers (36.4) were obtained on
      explants cultured on media incorporated with 2 MUM BA and 1 MUM NAA combinations.
      The in vitro-developed shoots rooted best on half-strength MS media incorporated
      with 2 MUM indole 3-butyric acid. Plantlets were effectively acclimatized in the
      greenhouse with 100% survival rate. The composition and contents of bioactive
      compounds such as carotenoids, tocopherol and fatty acids in shoot tissues of S.
      dasyphyllum were investigated using HPLC and GC-MS. The most abundant carotenoid
      in the shoot tissue was all-E-lutein (40.3-70.5 MUg g-1 FW) followed by 9'-Z
      neoxanthin (5.3-9.9 MUg g-1 FW), all-E-violaxanthin (4.4-8.2 MUg g-1 FW), and all
      E-beta-carotene (1.6-3.6 MUg g-1 FW). The alpha-tocopherol contents of in vitro
      raised shoots was 6.5-fold higher than shoots of greenhouse-grown plants. The
      primary fatty acids found in shoot tissues were alpha-linolenic acid (32.0
      39.3%), linoleic acid (27.4-38.2%), palmitic acid (13.3-15.5%), and stearic acid
      (5.2-12.2%). In all, summarizing the findings, the micropropagated S. dasyphyllum
      showed significant enrichment of valuable bioactive carotenoids (92.3 MUg g-1
      FW), tocopherols (14.6 MUg g-1 FW), and alpha-linolenic acid (39.3%) compared to
      their greenhouse counterparts. The protocol demonstrated here could be applied
      for the mass propagation and production of enhanced bioactive compounds from S.
      dasyphyllum with credibility.

PMID- 29062835
TI  - Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose
      Potency.
AB  - Exosomes are defined as submicron (30-150 nm), lipid bilayer-enclosed
      extracellular vesicles (EVs), specifically generated by the late endosomal
      compartment through fusion of multivesicular bodies with the plasma membrane.
      Produced by almost all cells, exosomes were originally considered to represent
      just a mechanism for jettisoning unwanted cellular moieties. Although this may be
      a major function in most cells, evolution has recruited the endosomal membrane
      sorting pathway to duties beyond mere garbage disposal, one of the most notable
      examples being its cooption by retroviruses for the generation of Trojan virions.
      It is, therefore, tempting to speculate that certain cell types have evolved an
      exosome subclass active in intracellular communication. We term this EV subclass
      "signalosomes" and define them as exosomes that are produced by the "signaling"
      cells upon specific physiological or environmental cues and harbor cargo capable
      of modulating the programming of recipient cells. Our recent studies have
      established that signalosomes released by mesenchymal stem/stromal cells (MSCs)
      represent the main vector of MSC immunomodulation and therapeutic action in
      animal models of lung disease. The efficacy of MSC-exosome treatments in a number
      of preclinical models of cardiovascular and pulmonary disease supports the
      promise of application of exosome-based therapeutics across a wide range of
      pathologies within the near future. However, the full realization of exosome
      therapeutic potential has been hampered by the absence of standardization in EV
      isolation, and procedures for purification of signalosomes from the main exosome
      population. This is mainly due to immature methodologies for exosome isolation
      and characterization and our incomplete understanding of the specific
      characteristics and molecular composition of signalosomes. In addition,
      difficulties in defining metrics for potency of exosome preparations and the
      challenges of industrial scale-up and good manufacturing practice compliance have
      complicated smooth and timely transition to clinical development. In this
      manuscript, we focus on cell culture conditions, exosome harvesting, dosage, and
      exosome potency, providing some empirical guidance and perspectives on the
      challenges in bringing exosome-based therapies to clinic.

PMID- 29062836
TI  - Prognostic Significance of Preoperative and Postoperative Complement C3 Depletion
      in Gastric Cancer: A Three-Year Survival Investigation.
AB  - OBJECTIVES: The role of complement system in predicting prognosis of gastric
      cancer (GC) remains obscured. This study aims to explore the incidence of
      complement C3 depletion and associated outcomes in GC patients. METHODS: between
      August 2013 and December 2013, 106 patients with gastric adenocarcinoma were
      prospectively analyzed. Plasma levels of complement C3 and C4 were detected at
      baseline, one day before surgery, and postoperative day 3, respectively. Patients
      with low C3 levels (<0.75 mg/mL) were considered as having complement depletion
      (CD), while others with normal C3 levels were included as control. The 3-year
      overall survival (OS), disease-free survival (DFS), and other outcomes were
      compared between both groups, with the CD incidence explored meanwhile. RESULTS:
      The CD incidence was 28.3% before surgery but increased to 37.7% after surgery.
      Preoperative CD was related to prolonged hospital stay (22.7 versus 19.2 day, P =
      0.032) and increased postoperative complications (33.3% versus 14.5%, P = 0.030)
      and hospital costs (P = 0.013). Besides, postoperative C3 depletion was
      significantly associated with decreased 3-year OS (P = 0.022) and DFS (P =
      0.003). Moreover, postoperative C3 depletion and advanced tumor stage were
      independent predictive factors of poor prognosis. CONCLUSIONS: Complement C3
      depletion occurring in gastric cancer was associated with poor short-term and
      long-term outcomes.

PMID- 29062837
TI  - Endothelinergic Contractile Hyperreactivity in Rat Contralateral Carotid to
      Balloon Injury: Integrated Role for ETB Receptors and Superoxide Anion.
AB  - Temporal consequences of neurocompensation to balloon injury on endothelinergic
      functionality in rat contralateral carotid were evaluated. Rats underwent balloon
      injury in left carotid and were treated with CP-96345 (NK1 antagonist).
      Concentration-response curves for endothelin-1 were obtained in contralateral
      (right) carotid at 2, 8, 16, 30, or 45 days after surgery in the absence or
      presence of BQ-123 (ETA antagonist), BQ-788 (ETB antagonist), or Tempol
      (superoxide-dismutase mimic). Endothelin-1-induced calcium mobilization was
      evaluated in functional assays carried out with BQ-123, BQ-788, or Tempol.
      Endothelin-1-induced NADPH oxidase-driven superoxide generation was measured by
      lucigenin chemiluminescence assays performed with BQ-123 or BQ-788. Endothelin-1
      induced contraction was increased in contralateral carotid from the sixteenth day
      after surgery. This response was restored in CP-96345-treated rats. Endothelium
      removal or BQ-123 did not change endothelin-1-induced contraction in
      contralateral carotid. This response was restored by BQ-788 or Tempol.
      Contralateral carotid exhibited an increased endothelin-1-induced calcium
      mobilization, which was restored by BQ-788 or Tempol. Contralateral carotid
      exhibited an increased endothelin-1-induced lucigenin chemiluminescence, which
      was restored by BQ-788. We conclude that the NK1-mediated neurocompensatory
      response to balloon injury elicits a contractile hyperreactivity to endothelin-1
      in rat contralateral carotid by enhancing the muscular ETB-mediated NADPH oxidase
      driven generation of superoxide, which activates calcium channels.

PMID- 29062838
TI  - Systematic Identification and Molecular Characteristics of Long Noncoding RNAs in
      Pig Tissues.
AB  - Long noncoding RNAs (lncRNAs) are non-protein-coding RNAs that are involved in a
      variety of biological processes. The pig is an important farm animal and an ideal
      biomedical model. In this study, we performed a genome-wide scan for lncRNAs in
      multiple tissue types from pigs. A total of 118 million paired-end 90 nt clean
      reads were obtained via strand-specific RNA sequencing, 80.4% of which were
      aligned to the pig reference genome. We developed a stringent bioinformatics
      pipeline to identify 2,139 high-quality multiexonic lncRNAs. The characteristic
      analysis revealed that the novel lncRNAs showed relatively shorter transcript
      length, fewer exons, and lower expression levels in comparison with protein
      coding genes (PCGs). The guanine-cytosine (GC) content of the protein-coding
      exons and introns was significantly higher than that of the lncRNAs. Moreover,
      the single nucleotide polymorphism (SNP) density of lncRNAs was significantly
      higher than that of PCGs. Conservation analysis revealed that most lncRNAs were
      evolutionarily conserved among pigs, humans, and mice, such as CUFF.253988.1,
      which shares homology with human long noncoding RNA MALAT1. The findings of our
      study significantly increase the number of known lncRNAs in pigs.

PMID- 29062840
TI  - Trajectories of Postload Plasma Glucose in the Development of Type 2 Diabetes in
      Japanese Adults.
AB  - We aimed to clarify how the trajectories of 1-hour postload plasma glucose (PG)
      and 2-hour PG were different in the development of type 2 diabetes. Using data of
      repeated health checkups in Japanese workers from April 2006 to March 2016,
      longitudinal changes of fasting, 1-hour, and 2-hour PG on the oral glucose
      tolerance test were analyzed with a linear mixed effects model. Of the 1464
      nondiabetic subjects at baseline, 112 subjects progressed to type 2 diabetes
      during the observation period (progressors). In progressors, 1-hour PG and 2-hour
      PG showed gradual increases with slopes of 1.33 +/- 0.2 and 0.58 +/- 0.2
      mg/dL/year, respectively, followed by a steep increase by which they attained
      diabetes. Until immediately before the diabetes transition, age- and sex-adjusted
      mean level of 2-hour PG was 149 +/- 2.7 mg/dL, 34 +/- 2.7 (30%) higher compared
      to nonprogressors, while that of 1-hour PG was 206 +/- 4.1 mg/dL, 60 +/- 4.3
      mg/dL (41%) higher compared to nonprogressors. In conclusion, diabetes transition
      was preceded by a mild elevation of 2-hour PG for several years or more. The
      elevation in 1-hour PG was larger than that of 2-hour PG until immediately before
      the transition to diabetes.

PMID- 29062842
TI  - Asymptomatic Malaria and its Challenges in the Malaria Elimination Program in
      Iran: a Systematic Review.
AB  - BACKGROUND: The objective of this study was to find an appropriate approach to
      asymptomatic malaria in elimination setting through a systematic review. METHODS:
      A broad search was conducted to find articles with the words 'malaria' in their
      titles and 'asymptomatic' or 'submicroscopic' in their texts, irrespective of the
      type of study conducted. The Cochrane, Medline/Pub Med, and Scopus databases, as
      well as Google Scholar were systematically searched for English articles and
      reports and Iran's databases-Iran Medex, SID and Magiran were searched for
      Persian reports and articles, with no time limitation. The study was
      qualitatively summarized if it contained precise information on the role of
      asymptomatic malaria in the elimination phase. RESULTS: Six articles were
      selected from the initial 2645 articles. The results all re-emphasize the
      significance of asymptomatic malaria in the elimination phase, and emphasize the
      significance of diagnostic tests of higher sensitivity to locate these patients
      and perform interventions to reduce the asymptomatic parasitic reservoirs
      particularly in regions of low transmission. However, we may infer from the
      results that the current evidence cannot yet specify an accurate strategy on the
      role of asymptomatic malaria in the elimination phase. CONCLUSION: To eliminate
      malaria, alongside vector control, and treatment of symptomatic and asymptomatic
      patients, active and inactive methods of case detection need to be employed. The
      precise monitoring of asymptomatic individuals and submicroscopic cases of
      malaria through molecular assays and valid serological methods, especially in
      regions where seasonal and low transmission exists can be very helpful at this
      phase.

PMID- 29062841
TI  - Propyl Gallate Exerts an Antimigration Effect on Temozolomide-Treated Malignant
      Glioma Cells through Inhibition of ROS and the NF-kappaB Pathway.
AB  - In this study, we demonstrated that temozolomide (TMZ) and propyl gallate (PG)
      combination enhanced the inhibition of migration in human U87MG glioma cells. PG
      inhibited the TMZ-induced reactive oxygen species (ROS) generation. The
      mitochondrial complex III and NADPH oxidase are two critical sites that can be
      considered to regulate antimigration in TMZ-treated U87MG cells. PG can enhance
      the antimigration effect of TMZ through suppression of metalloproteinase-2 and
      metalloproteinase-9 activities, ROS generation, and the NF-kappaB pathway and
      possibly provide a novel prospective strategy for treating malignant glioma.

PMID- 29062839
TI  - Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with
      Inflammation in Type 2 Diabetes Mellitus.
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which plays an
      important role in the central nervous system, and systemic or peripheral
      inflammatory conditions, such as acute coronary syndrome and type 2 diabetes
      mellitus (T2DM). BDNF is also expressed in several nonneuronal tissues, and
      platelets are the major source of peripheral BDNF. Here, we reviewed the
      potential role of BDNF in platelet reactivity in T2DM and its association with
      selected inflammatory and platelet activation mediators. Besides that, we focused
      on adipocytokines such as leptin, resistin, and adiponectin which are considered
      to take part in inflammation and both lipid and glucose metabolism in diabetic
      patients as previous studies showed the relation between adipocytokines and BDNF.
      We also reviewed the evidences of the antidiabetic effect of BDNF and the
      association with circulating inflammatory cytokines in T2DM.

PMID- 29062843
TI  - Utility of mtDNA-COI Barcode Region for Phylogenetic Relationship and Diagnosis
      of Five Common Pest Cockroaches.
AB  - BACKGROUND: Cockroaches are of vital importance medically and hygienically as
      they can disperse human pathogenic agents and are especially responsible for food
      contamination and spreading of food borne pathogens. In this study, part of mtDNA
      COI gene of five common pest cockroaches was tested for diagnostic and
      phylogenetic purposes. METHODS: We have described barcode region of mtDNA-COI
      gene of five cockroach species: Blattella germanica, Blatta orientalis,
      Periplaneta americana, Shelfordella lateralis, and Supella longipalpa, along with
      the development of a PCR-RFLP method for rapid detection and differentiation of
      these health pest species. RESULTS: The PCR generates a single 710 bp-sized
      amplicon in all cockroach specimens, followed by direct sequencing. AluI
      predicted from the sequencing data provided different RFLP profiles among five
      species. There was a significant intra-species variation within the American
      cockroach populations, but no genetic variation within other species.
      Accordingly, phylogenetic analysis demonstrates common monophyly for cockroach
      families in agreement with conventional taxonomy. However S. longipalpa
      (Ectobiidae) diverged as an early ancestor of other cockroaches and was not
      associated with other Ectobiidae. CONCLUSION: The PCR-RFLP protocol might be
      useful when the conventional taxonomic methods are not able to identify
      specimens, particularly when only small body parts of specimens are available or
      they are in a decaying condition. mtDNA-COI gene shows potentially useful for
      studying phylogenetic relationships of Blattodea order.

PMID- 29062844
TI  - A Retrospective Study on Scropionism in Iran (2002-2011).
AB  - BACKGROUND: Scorpion sting is a common medical emergency in Iran. The
      epidemiological features and control of such cases vary from south to north. This
      review will provide new information about the epidemiology of scorpion stings in
      different provinces of Iran. METHODS: In this descriptive retrospective study,
      data on scorpionism including incidence rates, mortality as well as locality from
      2002 to 2011were collected. RESULTS: Overall, 433203 victims of scorpion stings
      had been referred to health centers from of all of the 31 provinces. The
      incidence of scorpion stings in 100000 populations was from 54.8 to 66. The
      highest rate of scorpion stings occurred among the 25-34 yr old group. The
      highest incidence of scorpion stings during 2011 was observed in Khuzestan
      Province and the lowest number in Mazandaran Province. The peak number of human
      cases (scorpion stings) was recorded during May to August. CONCLUSION: Scorpion
      stings in Iran are high. It is necessary that physicians and health care
      professionals should be familiar with local scorpions, especially those that are
      potentially more dangerous than others, the effective treatment protocols, and
      supportive care as well as their control of scorpionism.

PMID- 29062845
TI  - Efficacy of AloeVera Cream in the Treatment of Paederus Dermatitis in Mice.
AB  - BACKGROUND: Dermatitis caused by Paederus beetle involves many people around the
      world, especially Iran. The symptoms include redness, itching and severe
      irritation. This study evaluated the effectiveness of the Aloevera cream on the
      treatment of dermatitis caused by Paederus beetles. METHODS: Forty male 6-8 weeks
      BALB/C mice were randomly divided into four groups of 10 mice. After removing the
      mice's back hair, the backs of mice were marked by a circle with a diameter of 3
      mm. The Paederus beetles were collected from Babol in Mazandaran Province,
      northern Iran and transferred to the animal lab of Aja University of Medical
      Sciences, Tehran, Iran. The end of abdominal segment Paederus was cut with
      scissors and hemolymph content was pushed by forceps on the circle. Only
      hemolymph of one Paederus applied to the back of each mouse. Groups 1, 2, 3 and 4
      were treated with the base (vehicle), dexamethasone 0.1%, Aloevera 0.5% and
      Aloevera 2% creams respectively. After 2 days, dermatitis appeared. Then the
      mentioned creams were applied on the mice once a day. The wound area was measured
      every day. Dermatitis surface area under curve (AUC) of each mouse was calculated
      for 17 days after induction of dermatitis. Statistical analysis of ANOVA was
      used. RESULTS: Application of Aloevera 0.5% and 2% significantly reduced the
      healing duration and dermatitis area in comparison with the vehicle and
      dexamethasone cream (P< 0.05). But dexamethasone had no significant effect on the
      healing of dermatitis as compared to vehicle. CONCLUSION: Aloevera may clinically
      effective in the treatment of Paederus dermatitis.

PMID- 29062846
TI  - Larval Habitats Characteristics of Mosquitoes (Diptera: Culicidae) in North-East
      of Iran.
AB  - BACKGROUND: There are unorganized, published documents about the ecology of
      mosquitoes (Diptera: Culicidae) in northeastern part of Iran. The purpose of this
      study was to determine the distribution and characteristics of larval habitats of
      Culicidae in Kalaleh County. METHODS: Larvae were collected using dipping method
      and adults by human landing catch technique during April-October, 2012. Larval
      habitat characteristics were recorded such as vegetation status, and sunlight,
      water situation. Lacto-phenol and de Faure's media were used for conserving and
      mounting samples. Data were analyzed using SPSS statistical software, version
      11.5. RESULTS: Out of the 395 larvae collected, 332 were adult mosquitoes
      comprising; Culiseta, Culex, Anopheles and Ochlerotatus genera and 14 species
      including An. superpictus, An. maculipennis s.l., An. hyrcanus, An. psudopictus,
      An. claviger, Culex pipiens, Cx. theileri, Cx. perexiguus, Culiseta
      longiareolata, Cs. subochrea, Ochlerotatus caspius, Oc. echinus and Oc.
      geniculatus. Culex pipiens larvae were predominant (27.6%) and Cs. subochrea (1%)
      was found as the lowest species in terms of number. In the adult form, Cx.
      pipiens (28.9%) was predominant whereas, Cs. subochrea and Cx. perexiguus were
      reported to have had the lowest frequency. CONCLUSION: The larvae of An.
      superpictus and An. maculipennis species as the main vectors of malaria in north
      of Iran were reported in permanent habitats with clear water and vegetation, full
      and partial sunlight situations and muddy as well as sandy substrates that are
      important in larvicide application programs. Exclusive studies are necessary to
      diagnose An. maculipennis species complex using molecular and morphological
      analysis in the future.

PMID- 29062847
TI  - Evaluation of Larvicidal Activity of Essential Oil from Leaves of Coccinia
      grandis against Three Mosquito Species.
AB  - BACKGROUND: To study the chemical constituents and larvicidal activity of
      essential oil extracted from the leaves of Coccinia grandis against three
      mosquito species. METHODS: Essential oil was extracted by hydro distillation
      using clevenger apparatus and was analyzed for chemical constituents by gas
      chromatography-mass spectrophotometry (GC-MS). Larvicidal activity was recorded
      after 12 and 24h of post-exposure against three mosquito species, Anopheles
      stephensi, Aedes aegypti and Culex quinquefasciatus. Dead larvae were identified
      when they failed to move after probing with a needle in the siphon or cervical
      region. The LC50 and LC90 values for three mosquito larvae were calculated by
      Probit analysis. RESULTS: The GC-MS analysis revealed that essential oil contains
      23 different constituents. Out of these 23 constituents, major constituents
      identified were n-tetracosane (39.18%), n-eicosane (30.04%), tetratriacotane
      (2.97%), 7-octadecanal (2.81%), and tricosane (2.31%). Essential oil from leaves
      of Coccinia grandis exhibited significant larvicidal activity against An.
      stephensi with LC50 and LC90 values 39.41ppm and 123.24ppm, respectively. This
      was followed by Ae. aegypti and Cx. quinquefasciatus with LC50 and LC90 values of
      48.20ppm, 131.84ppm and 52.80ppm, 135.48ppm, respectively after 24h of exposure.
      CONCLUSION: The results could be useful in developing a cost effective,
      ecofriendly, region specific and practical strategy for the control of mosquito
      vectors.

PMID- 29062848
TI  - New Host Records for Haemoproteus Spp. (Apicomplexa: Haemosporidiasina) in
      Passeriformes from North-West of Iran.
AB  - BACKGROUND: The intracellular protozoan parasites of the genus Haemoproteus occur
      in different avian hosts all over the world. Various genus of blood sucking
      insects' families such as Hippoboscidae and Ceratopogonidae could transmit
      Haemoproteus in avian hosts. There are very limited number of studies on wild
      infected birds with blood parasites in Iran, so the aim of this study was to
      determine the frequency of Haemoproteus spp. infection in passerine birds from
      northwest of Iran. METHODS: Passerines were collected from four different
      localities in Zanjan Province, northwest Iran during June to August 2014.
      RESULTS: Of 86 passerines, we found Haemoproteus infection in 19 (22.09%)
      individuals. In general, 15 bird species were observed for haemosporidians, of
      which 53% were infected. CONCLUSION: Three species of passerines: Petronia
      petronia, Sitta tephronota and Acrocephalus melanopogon are new host records for
      Haemoproteus infection in the world. Results acquired by this study support
      widespread distribution of Haemoproteus in passerines and illustrated the
      prevalence of Haemoproteus species in wild birds of northwest of Iran.
      Conclusively, our study specified that more investigations are needed to reach
      exact prevalence rate in different families of birds in Iran.

PMID- 29062849
TI  - Fauna and Geographical Distribution of Scorpions in Ilam Province, South Western
      Iran.
AB  - BACKGROUND: Scorpions' stings and their own mortalities place them among the most
      important health and medical problems. The dreadful features and especially their
      poisonous stings are considered a major cause of human stress and
      abhorrence/phobia. The current study aimed to study the scorpion fauna of Ilam
      Province, south western Iran in order to manage scorpionism related problems.
      METHODS: In this field-laboratory investigation during March 2014 to February
      2015, different parts of Ilam Province were surveyed. Nine sampling parts were
      selected based on geographical situation, scorpionism reports, weather, flora,
      and local data. Capturing scorpion was done employing a black light, and a long
      forceps from dusk to midnight. The collected scorpions were placed to 70% ethyl
      alcohol. All specimens were determined based on the valid taxonomic keys,
      furthermore their sexes were studied. RESULTS: Out of the 391 collected
      scorpions, 11 species were identified as follows: Hottentotta saulcyi, Mesobuthus
      eupeus, Compsobuthus matthiesseni, Razianus zarudnyi, Hemiscorpius lepturus,
      Androctonus crassicauda, Orthochirus iranus, Odontobuthus bidentatus, Buthacus
      macrocentrus, Scorpio maurus, and Polisius persicus. CONCLUSION: Eleven species
      of Buthidae, Scorpionidae and Hemiscorpiidae families from high risk areas were
      identified. Despite the low surface of the province, such different species
      reveals a diverse scorpion fauna that, in turn, shows good and suitable habits of
      scorpions, as considered by health staff.

PMID- 29062850
TI  - Species Diversity and Distributional Pattern of Cockroaches in Lahore, Pakistan.
AB  - BACKGROUND: Cockroaches are found as the most common urban pests of tropical
      countries, prompting economic and serious health risk problem for humans by
      carrying microbes and allergens, acting as vector for various pathogens of
      diseases. The present study was conducted from April 2013 to March 2014 in
      various human dwelling localities of urban area of district Lahore, Pakistan.
      METHODS: Cockroaches were collected randomly by hand, food baited and sticky
      traps throughout the year. Four species of cockroaches (Periplaneta Americana (P.
      amercana), Blattella germanica (B. germanica), Blatta orientalis (B. orientalis),
      and Blatta lateralis (B. lateralis) were collected and identified from the study
      site. RESULTS: B. germanica was the most dominant indoor species with highest
      diversity indices in study areas. Overall cockroach species diversity was highest
      in July-September, 2013 with highest Simpson index of diversity and Shannon index
      as well. P. americana was found second broadly distributed in the study area
      followed by B. orientalis and B. lateralis were intermediately distributed in
      residential areas and narrowly distributed in hospitals. Residential areas and
      hospitals were highly infested with B. germanica followed by P. americana.
      Population index of B. germanica for hospitals was double than residential areas.
      B. lateralis was observed as displacing B. orientalis in outdoor habitat through
      competing with its habitat and food sources. CONCLUSION: The infestation rate of
      different species depends on availability of food sources, sanitary conditions
      and climatic conditions. Cockroach infestation can be controlled with knowledge
      about their biology and behavior, attention to sanitation and effective use of
      commercial insecticides.

PMID- 29062852
TI  - Bio-Pesticides: New Tool for the Control of Aedes (Stegomyia) albopictus
      (Culicidae: Diptera) in Pakistan.
AB  - BACKGROUND: Application of plant extracts as mosquito control strategy was
      practiced from centuries. These are easily available, non-toxic, biodegradable
      and exhibit broad-spectrum target specific activities against larval stages of
      mosquitoes. METHODS: Different potential parts of locally grown plants, seeds of
      nutmeg (Myristica fragrans), peel of musambi (Citrus sinensis), leaves of babuna
      (Matricaria chamomilla), mint (Mentha spicata) and ginger rhizome (Zingiber
      officinale) selected and evaluated for their larvicidal properties against Aedes
      (Stegomyis) albopictus. Oils were extracted through steam distillation process
      and extracts were evaluated as per WHO 2005 guidelines for testing of
      insecticides against larvae of mosquitoes. RESULTS: Among the five plant
      extracts, C. sinensis had the lowest LC50 (400.81ppm) while M. fragrans had the
      highest LC50 value (710.30ppm) respectively after 24h of exposure. In terms of %
      age mortality, a series of concentrations (300-800ppm) gave high % mortality in
      case of C. sinensis while M. fragrans gave low % age mortality. CONCLUSION: All
      the five plant species have larvicidal effects to certain extant and C. sinensis
      had great potential. Further small-scale field trials with the extracts of the
      most promising one (C. sinensis) shall be conducted to determine operational
      feasibility.

PMID- 29062851
TI  - Larvicidal Activities of Indigenous Bacillus thuringiensis Isolates and Nematode
      Symbiotic Bacterial Toxins against the Mosquito Vector, Culex pipiens (Diptera:
      Culicidae).
AB  - BACKGROUND: The incidence of mosquito-borne diseases and the resistance of
      mosquitoes to conventional pesticides have recently caused a panic to the
      authorities in the endemic countries. This study was conducted to identify native
      larvicidal biopesticides against Culex pipiens for utilization in the battle
      against mosquito-borne diseases. METHODS: Larvicidal activities of new indigenous
      Bacillus thuringiensis isolates and crude toxin complexes (TCs) of two nematode
      bacterial-symbionts, Photorhabdus luminescens akhurstii (HRM1) and Ph.
      luminescens akhurstii (HS1) that tested against Cx. pipiens. B. thuringiensis
      isolates were recovered from different environmental samples in Saudi Arabia, and
      the entomopathogenic nematodes, Heterorhabditis indica (HRM1) and He. sp (HS1)
      were isolated from Egypt. Larvicidal activities (LC50 and LC95) of the
      potentially active B. thuringiensis strains or TCs were then evaluated at 24 and
      48h post-treatment. RESULTS: Three B. thuringiensis isolates were almost as
      active as the reference B. thuringiensis israelensis (Bti-H14), and seven
      isolates were 1.6-5.4 times more toxic than Bti-H14. On the other hand, the TCs
      of the bacterial symbionts, HRM1 and HS1, showed promising larvicidal activities.
      HS1 showed LC50 of 2.54 folds that of HRM1 at 24h post-treatment. Moreover,
      histopathological examinations of the HS1-treated larvae showed deformations in
      midgut epithelial cells at 24h post-treatment. CONCLUSION: Synergistic activity
      and molecular characterization of these potentially active biocontrol agents are
      currently being investigated. These results may lead to the identification of eco
      friend mosquito larvicidal product(s) that could contribute to the battle against
      mosquito-borne diseases.

PMID- 29062853
TI  - Faunistic Study of the Aquatic Arthropods in a Tourism Area in Northern Iran.
AB  - BACKGROUND: Aquatic insects are very abundant and divers groups of insects that
      are associated with an aquatic or semiaquatic environment in one or more of their
      life stages. These insects have been, in some cases, well studied because they
      are vectors of several diseases. This is the first comprehensive faunistic study
      of aquatic insects from Babol County. The results may provide basic data for
      further taxonomic and ecological studies of aquatic insects as biological control
      agent or classification of water quality for the country. METHODS: The specimens
      were collected using different methods including: D-frame net collector, standard
      mosquito dipper (350ml), Sweep-Netting and plastic pipette. Sampling carried out
      in different part of breading places in several times. RESULTS: During this study
      a total of 196 aquatic specimens were collected from different habitats and were
      morphologically identified including 18 families classified in 6 orders: Diptera,
      Trichoptera, Ephemeroptera, Plecoptera, Hemiptera and Odonata. Babol and Amol
      district in Mazandaran Province are located in humid climate regions with
      suitable ecological factors of humidity, moderate temperature and the variety of
      plant species. There are different species of aquatic insects in different
      habitats. CONCLUSION: The results will provide information for biodeveristy,
      species richness, their role for biological control as well as calcification of
      rivers based on abundance of aquatic insects. Therefore the understanding of
      ecological specifications of aquatic insects could provide a clue for further
      Arthropod-borne disease control. Additionally aquatic insect could be used for
      classification of water bodies.

PMID- 29062854
TI  - Effect of Different Diets on Lifetime of Brown-Banded Cockroaches, Supella
      longipalpa (Blattodea: Blattellidae).
AB  - BACKGROUND: The brown-banded cockroach, Supella longipalpa, is not as common as
      the German cockroach in Iran. This species seeks out areas that are very warm
      most of the time, and prefer warmer area than what German cockroaches prefer.
      There is relationship between development of instars and diet of cockroaches. The
      aim of this study was to determine the effect of different diets on biology, life
      cycle on nymphal stages of S. longipalpa in laboratory condition prior to
      investigate the insecticide resistance status of this species in residence area
      in Iran. METHODS: The cockroaches were reared in the insectary of School of
      Public Health, Tehran University of Medical Sciences, condition and the
      population divided in four equal groups. The effect of four different diets on
      life cycle of S. longipalpa was studied to determine the effect of them on the
      lifetime of each nymphal stage. RESULTS: The diets significantly affected on
      growth and development of immature life stages of S. longipalpa. Based on
      introduced diets to the cockroache populations, total immature life cycle was 54,
      58, 60 and 66 d for diets 2,4,1, and 3 relatively. However, the overall lifetime
      of S. longipalpa in average was about 225 days. CONCLUSION: As far as urban pest
      control is concerned, the result of this study will facilitate any operational
      programs for control of S. longipalpa. Among the different tested diets, diets 2
      and 4 with less duration would be recommended for rearing of S. longipalpa in
      laboratory condition.

PMID- 29062855
TI  - House Dust Mite Prevalence in the House of Patients with Atopic Dermatitis in
      Mashhad, Iran.
AB  - BACKGROUND: Being exposed to house dust mites intensifies atopic dermatitis. This
      study has investigated the contamination rate with Dermatophagoides mites in
      patient's residential home with atopic dermatitis. METHODS: In this cross
      sectional study, 40 patients took part with atopic dermatitis (positive or
      negative for mites by prick Dermal Test). Samples were collected from 3 locations
      (living room, bedroom and bed) by vacuum cleaner. Dust samples (transferred to
      freezer -20  degrees C) were examined by direct method and flotation. The data
      were analyzed using statistical SPSS vr.20 software. RESULTS: Twenty patients of
      positive prick test included 8 (40%) male and 12 (60%) female. The results of
      direct observation of mites: 7 cases (35%) in bedding sheets, 6 cases (30%)
      bedrooms' carpet, 3 cases (15%) living room's carpet. Twenty patients of negative
      prick test included 8 (40%) male and 12 (60%) female. Only mites were found (5%)
      in living room's carpets of negative prick test patients. Dermatophagoides
      pteronyssinus was more frequent than Dermatophagoides farinae. (98% vs 83%).
      CONCLUSION: Fifty-five percent of residential homes of prick test positive
      patients and only 5% of residential homes of prick test negative patients were
      positive for mite. Sunshine provided home had fewer mites than home where
      sunshine is not provided. Prick test positive patients used handmade carpets more
      than machine made ones. In positive prick test patients, mites were found in bed
      sheet and bedroom's carpet more than negative prick test patient's sheets and
      carpets.

PMID- 29062856
TI  - Synthesis and Chemometrics of Thymol and Carvacrol Derivatives as Larvicides
      against Aedes aegypti.
AB  - BACKGROUND: Thymol and carvacrol have previously demonstrated larvicidal activity
      against Aedes aegypti (Diptera: Culicidae). In view of this fact, it was of our
      interest to obtain synthetic derivatives and evaluate their larvicidal activity
      on Ae. aegypti larvae. METHODS: Structural modifications were performed on thymol
      and carvacrol in an effort to understand the functional groups necessary for
      modulating their activities and to lead possibly to more effective larvae control
      agents. The derivatives were further subjected to SAR and computational studies
      (molecular modeling and chemometric tools (CPCA and PCA)) to extract structural
      information regarding their larvicidal properties. Field collected and
      Rockefeller populations of Ae. aegypti were used. RESULTS: Carvacrol and thymol
      exhibited LC50 of 51 and 58ppm for field collected larvae, respectively.
      Carvacrol derivatives exhibited LC50 ranging from 39 to 169ppm, while thymol
      derivatives exhibited LC50 ranging from 18 to 465ppm. Substitution of the acidic
      proton of carvacrol by esters, ethers, and acetic acid resulted in either
      maintenance or reduction of potency. CONCLUSION: Thymol derivatives were, to a
      certain extent, more efficient larvicides against Ae. aegypti than carvacrol
      derivatives, particularly to Rockefeller larvae. The chemometrics tools applied
      in this study showed that the independent variables indicate a mixed profile.
      Nevertheless, hydrophobic interactions increased the larvicidal activity.

PMID- 29062857
TI  - Seroprevalence of Visceral Leishmaniasis in Children up to 12 Years old Among
      Nomadic Tribes from Rural Areas of Pars Abad, Northwestern Iran: an Observational
      Study in 2015.
AB  - BACKGROUND: Since Pars Abad district had been known as a focus of visceral
      leishmaniasis (VL) in Ardabil Province but the prevalence of the disease in
      nomadic tribes has not been determined, thus, this study was conducted. METHODS:
      This descriptive cross-sectional study was conducted on children up to 12yr old
      of nomadic tribes from Pars Abad County, Ardabil Province, Iran in 2015. For each
      individual, a questionnaire including age, sex, clinical manifestations, history
      of disease, and contact with reservoir hosts of VL were completed, separately. To
      determine VL seroprevalence, blood samples were collected from the children and
      after centrifugation, the plasma samples were tested using Direct Agglutination
      Test (DAT) for detection of anti-Leishmania infantum antibodies. Statistical
      analyses were performed using SPSS16. RESULTS: From 776 children up to 12yr old,
      2 (0.25%) showed anti-L. infantum antibodies at titers 1:1600 and only one case
      (0.13%) showed anti-Leishmania antibodies at titers 1:3200. The child with anti
      L. infantum antibodies titers of 1:3200 showed mild fever for more than 2 months
      period, paleness, weakness and mild splenomegaly. After physical examination and
      confirmation of VL (kala-azar), the patient was treated with antileishmanial
      drugs. CONCLUSION: The findings indicated that L. infantum infection is being
      circulated with low prevalence in nomadic tribes of Pars Abad but it is necessary
      that the surveillance system is regularly monitored among physicians and public
      health managers in the studied areas.

PMID- 29062858
TI  - Identification of Hymenolepis diminuta Cysticercoid Larvae in Tribolium castaneum
      (Coleoptera: Tenebrionidae) Beetles from Iran.
AB  - BACKGROUND: Hymenolepis diminuta is a cestod of rodents and rarely infects
      humans. Infection in humans is via ingestion of infected insects. This study was
      aimed to detect H. diminuta cysticercoids in red flour beetles, Tribolium
      castaneum, and cockroaches originated from different regions of Iran. METHODS:
      The red flour beetles and cockroaches were collected from local bakeries in five
      cities including Tehran, Ahvaz, Kazerun, and Sabzevar during 2010-2011. Some
      beetles and cockroaches were colonized in insectary and adults from F1 generation
      were fed on H. diminuta eggs. Both laboratory-infected and field-collected
      samples were dissected and examined for cysticercoids. Detection of H. diminuta
      DNA in T. castaneum beetles was performed by targeting a partial sequence of
      Ribosomal gene. RESULTS: Except the beetles from Ahvaz, all specimens were
      negative for cysticercoid by microscopy. Of the four dissected beetles from
      Ahvaz, one harbored 12 cysticercoids. Also, 110 (52%) of laboratory-infected
      beetles showed infection with an average of 12-14 larvae. None of the cockroaches
      was infected. Two beetles from Ahvaz, including the remainder of the microscopic
      positive specimen, yielded the expected amplicon in PCR assay. The H. diminuta
      DNA sequences generated in this study were identical and matched 97-100% with
      similar sequences from GenBank database. CONCLUSION: Lack of infection in the
      majority of beetles may reflect a low rat infestation rate in those areas,
      alternatively, the examined specimens might not have been the representative
      samples of the T. castaneum populations.

PMID- 29062859
TI  - Suicide Risk Among Transgender People: A Prevalent Problem in Critical Need of
      Empirical and Theoretical Research.
AB  - Transgender individuals are at increased risk for suicide relative to
      nontransgender people. Despite this, research on transgender people's risk for
      suicide mirrors their marginalization at the societal level; there is simply not
      enough research dedicated to understanding increased suicide risk among
      transgender people. This article presents a brief review of what is known
      regarding the prevalence and correlates of suicide-related thoughts and behaviors
      among transgender people and offers perspective regarding what theories of
      suicide may be pertinent to understanding and addressing increased suicide risk
      within this population. We also summarize strengths and limitations of the
      current body of work to provide impetus for additional and improved research on
      this important problem.

PMID- 29062860
TI  - In Utero ART Exposure and Birth and Early Growth Outcomes Among HIV-Exposed
      Uninfected Infants Attending Immunization Services: Results From National PMTCT
      Surveillance, South Africa.
AB  - BACKGROUND: Despite the recognized benefit of antiretroviral therapy (ART) for
      preventing and treating HIV, some studies have reported adverse birth outcomes
      with in utero ART exposure. We evaluated the effect of infant in utero HIV and
      ART exposure on preterm delivery (PTD), low birth weight (LBW), small for
      gestational age (SGA), and underweight for age (UFA) at 6 weeks. METHODS: We
      surveyed 6179 HIV-unexposed-uninfected (HUU) and 2599 HIV-exposed-uninfected
      (HEU) infants. HEU infants were stratified into 3 groups: ART, Zidovudine alone,
      and no antiretrovirals (None). The ART group was further stratified to explore
      pre- or postconception exposure. Multivariable logistic regression evaluated
      effects of HIV and ARV exposure on the outcomes. RESULTS: We found higher odds of
      PTD, LBW, SGA, and UFA in HEU than HUU infants. HEU in the None group (adjusted
      odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.2-3.0) or those whose
      mothers initiated ART preconception (AOR, 1.7; 95% CI, 1.1-2.5) had almost twice
      the odds of PTD than infants whose mothers started ART postconception, but no
      increased odds for other outcomes. CONCLUSIONS: There was an association between
      preconception ART and PTD. As ART access increases, pregnancy registers or
      similar surveillance should be in place to monitor outcomes to inform future
      policy.

PMID- 29062861
TI  - Pneumocystis PCR: It Is Time to Make PCR the Test of Choice.
AB  - BACKGROUND: The testing strategy for Pneumocystis at the Cleveland Clinic changed
      from toluidine blue staining to polymerase chain reaction (PCR). We studied the
      differences in positivity rates for these assays and compared each with the
      detection of Pneumocystis in companion specimens by cytology and surgical
      pathology. METHODS: We reviewed the results of all Pneumocystis test orders 1
      year before and 1 year after the implementation of a Pneumocystis-specific PCR.
      We also reviewed the corresponding cytology and surgical pathology results, if
      performed. Finally, we reviewed the medical records of patients with rare
      Pneumocystis detected by PCR in an effort to differentiate colonization vs true
      disease. RESULTS: Toluidine blue staining and surgical pathology had similar
      sensitivities and negative predictive values, both of which were superior to
      cytology. There was a >4-fold increase in the annual detection of Pneumocystis by
      PCR compared with toluidine blue staining (toluidine blue staining: 11/1583
      [0.69%] vs PCR: 44/1457 [3.0%]; chi-square P < .001). PCR detected 1 more case
      than surgical pathology and was far more sensitive than cytology. Chart review
      demonstrated that the vast majority of patients with rare Pneumocystis detected
      were immunosuppressed, had radiologic findings supportive of this infection, had
      no other pathogens detected, and were treated for pneumocystosis by the clinical
      team. CONCLUSION: PCR was the most sensitive method for the detection of
      Pneumocystis and should be considered the diagnostic test of choice. Correlation
      with clinical and radiologic findings affords discrimination of early true
      disease from the far rarer instances of colonization.

PMID- 29062862
TI  - High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals
      Initiating Antiretroviral Therapy in Botswana.
AB  - BACKGROUND: Hepatitis B surface antigen (HBsAg)-negative but hepatitis B virus
      (HBV) DNA-positive infection-known as occult hepatitis B infection (OBI)-occurs
      in 1% to >15% of HIV-positive individuals in the United States and South Africa,
      respectively. However, there are no data on OBI from Botswana, a country known to
      be hyperendemic for chronic HBV infection and to have a significant HIV burden.
      METHODS: Two hundred seventy-two adults enrolled in an HIV treatment study of
      tenofovir/emtricitabine as the nucleoside backbone who were previously determined
      to be HBsAg negative were tested for HBV DNA at baseline and 1 year after
      initiation of highly active antiretroviral therapy (HAART). RESULTS: HBV DNA was
      detected in 72 of 272 (26.5%). Six individuals (8.3%) had HBV DNA levels greater
      than 200 IU/mL, and the highest viral load was 3280 IU/mL. Of 65 participants
      with OBI evaluated at 12 months after initiating HAART, only 1 (1.5%) had
      detectable HBV DNA. CONCLUSIONS: Occult HBV infection is quite common in HIV
      infected patients in Botswana, although its impact on the course of HIV disease
      progression is unknown. The suppression of occult HBV DNA levels by
      tenofovir/emtricitabine suggests an effective therapeutic option, although the
      long-term suppressive abilities remain unstudied.

PMID- 29062863
TI  - The vacuolar H+ ATPase V0 subunit d2 is associated with chondrocyte hypertrophy
      and supports chondrocyte differentiation.
AB  - Chondrocyte hypertrophy makes important contributions to bone development and
      growth. We have investigated a number of novel cartilage genes identified in a
      recent transcriptomic study to determine whether they are differentially
      expressed between different zones of equine foetal growth cartilage. Twelve genes
      (ATP6V0D2, BAK1, DDX5, GNB1, PIP4K2A, RAP1B, RPS7, SRSF3, SUB1, TMSB4, TPI1 and
      WSB2) were found to be more highly expressed in the zone of hypertrophic
      chondrocytes than in the reserve or proliferative zones, whereas FOXA3 and
      SERPINA1 were expressed at lower levels in the hypertrophic zone than in the
      reserve zone. ATP6V0D2, which encodes vacuolar H+ ATPase (V-ATPase) V0 subunit d2
      (ATP6V0D2), was selected for further study. Immunohistochemical analysis of
      ATP6V0D2 in growth cartilage showed stronger staining in hypertrophic than in
      reserve zone or proliferative chondrocytes. Expression of ATP6V0D2 mRNA and
      protein was up-regulated in the mouse chondrocytic ATDC5 cell line by conditions
      inducing expression of hypertrophy-associated genes including Col10a1 and Mmp13
      (differentiation medium). In ATDC5 cells cultured in control medium, knockdown of
      Atp6v0d2 or inhibition of V-ATPase activity using bafilomycin A1 caused a
      decrease in Col2a1 expression, and in cells cultured in differentiation medium
      the two treatments caused a decrease in nuclear area. Inhibition of V-ATPase, but
      not Atp6v0d2 knockdown, prevented the upregulation of Col10a1, Mmp13 and Vegf by
      differentiation medium, while Atp6v0d2 knockdown, but not inhibition of V-ATPase,
      caused an increase in the number of ATDC5 cells cultured in differentiation
      medium. These observations identify ATP6V0D2 as a novel chondrocyte hypertrophy
      associated gene. The results are consistent with roles for V-ATPase, both
      ATP6V0D2-dependent and -independent, in supporting chondrocyte differentiation
      and hypertrophy.

PMID- 29062864
TI  - Influence of gastrointestinal events on treatment of osteoporosis in Asia-Pacific
      women: Perspectives from physicians in the MUSIC OS-AP study.
AB  - BACKGROUND: The objectives of the physician survey component of the MUSIC OS-AP
      study were to describe physicians' approaches to treatment of women with
      postmenopausal osteoporosis and to understand the influence of gastrointestinal
      (GI) events on treatment in clinical practice. METHODS: Physicians were recruited
      from 5 Asia-Pacific countries. Questionnaires collected information about
      physicians' standard practices for treatment of patients with osteoporosis, as
      well as their perspectives on the influence of GI events on osteoporosis
      treatment approaches. RESULTS: A total of 59 physicians participated in the
      study. The most frequently prescribed or recommended treatments were vitamin D
      (84% of patients), calcium (82%), and oral bisphosphonates (59%). When choosing a
      medication for treatment-naive patients, GI sensitivity was often or always a
      factor for 79% of physicians. Among physicians not prescribing pharmacologic
      treatment, a mean of 18% of non-prescriptions were due to GI sensitivity. For
      patients with pre-existing GI conditions, physicians most frequently ranked use
      of non-oral osteoporosis medication as the first treatment strategy (47%),
      followed by co-prescription with a proton pump inhibitor or other gastro
      protective agent (31%). For patients developing GI symptoms after starting
      pharmacologic treatment, the most frequently first-ranked management strategy was
      to check if patients were taking their osteoporosis medication correctly as
      prescribed (64%), followed by temporary discontinuation of the medication (i.e.,
      a drug holiday) until GI events have resolved (31%) and co-prescription with a
      proton pump inhibitor or other gastroprotective agent (24%). CONCLUSIONS: These
      results suggest that GI events influence the prescribing practices of physicians
      in the Asia-Pacific region and sometimes result in non-treatment of women with
      osteoporosis.

PMID- 29062865
TI  - Dataset on Investigating the role of onsite learning in the optimisation of craft
      gang's productivity in the construction industry.
AB  - The data presented in this article is an original data on "Investigating the role
      of onsite learning in the optimisation of craft gang's productivity in the
      construction industry". This article describes the constraints influencing craft
      gang's productivity and the influence of onsite learning on the blockwork craft
      gang's productivity. It also presented the method of data collection, using a
      semi-structured interview and an observation method to collect data from
      construction organisations. We provided statistics on the top most important
      constraints affecting the craft gang's productivity using 3-D Bar charts. In
      addition, we computed the correlation coefficients and the regression model on
      the influence of onsite learning on craft gang's productivity using the man-hour
      as the dependent variable. The relationship between blockwork inputs and cycle
      numbers was determined at 5% significance level. Finally, we presented data
      information on the application of the learning curve theory using the unit
      straight-line model equations and computed the learning rate of the observed
      craft gang's blockwork repetitive work.

PMID- 29062866
TI  - Physicochemical data on aqueous polymeric systems of methyl cellulose and lambda-
      and kappa-carrageenan: SAXS, rheological, densitometry, and sound velocity
      measurements.
AB  - General as well as more specific physicochemical data obtained by studying the
      structure and various dynamical properties of aqueous polymer systems of methyl
      cellulose, [Formula: see text]carrageenan, and [Formula: see text]carrageenan are
      presented in graphical and numeric tabular form. The data provide basic polymer
      characterization info as also a specific structural and dynamical info for
      aqueous solutions of three industrially very important polymers (food additives)
      that are available commercially. The commercial availability has much bigger
      impact to applications, research and connected advances, when the basic
      substances are well characterized - a feature that is still missing for many
      commercially available polymers unfortunately.

PMID- 29062867
TI  - Sediment textural characteristics and elemental distribution in the core
      sediments, Pullivasal and Kurusadai Island, Gulf of Mannar, Southeast coast of
      India.
AB  - Two core samples were collected in order to assess the textual characteristics
      and elemental distribution of the sediments, from the lagoonal environment of
      Pullivasal and Kurusadai island, Gulf of Mannar, Southeast coast of India. The
      distribution of the organic matter and calcium carbonate is chiefly controlled by
      the coral debris, shell fragments and mangrove litters. The elemental
      distribution is controlled by natural process and other trace elements are
      controlled by anthropogenic land based activities.

PMID- 29062868
TI  - Data on physicochemical properties of active films derived from plantain
      flour/PCL blends developed under reactive extrusion conditions.
AB  - The data given below relates to the research paper entitled: "Eco-friendly films
      prepared from plantain flour/PCL blends under reactive extrusion conditions using
      zirconium octanoate as a catalyst", recently published by our research group [1].
      This article provides information concerning the physicochemical properties of
      the above-mentioned film systems: thickness, density, opacity, moisture content
      and surface moisture.

PMID- 29062869
TI  - Gel-based and gel-free proteome data associated with controlled deterioration
      treatment of Glycine max seeds.
AB  - Data presented here are associated with the article: "In-depth proteomic analysis
      of soybean (Glycine max) seeds during controlled deterioration treatment (CDT)
      reveals a shift in seed metabolism" (Min et al., 2017) [1]. Seed deterioration is
      one of the major problems, affecting the seed quality, viability, and vigor in a
      negative manner. Here, we display the gel-based and gel-free proteomic data,
      associated with the CDT in soybean seeds. The present data was obtained from 2
      DE, shotgun proteomic analysis (label-free quantitative proteomic analysis) using
      Q-Exactive, and gene ontology analysis associated with CDT in soybean seeds (Min
      et al., 2017) [1].

PMID- 29062870
TI  - Datasets on the statistical properties of the first 3000 squared positive
      integers.
AB  - The data in this article are as a result of a quest to uncover alternative
      research routes of deepening researchers' understanding of integers apart from
      the traditional number theory approach. Hence, the article contains the
      statistical properties of the digits sum of the first 3000 squared positive
      integers. The data describes the various statistical tools applied to reveal
      different statistical and random nature of the digits sum of the first 3000
      squared positive integers. Digits sum here implies the sum of all the digits that
      make up the individual integer.

PMID- 29062871
TI  - Forecasting the outcome of a time-varying Bernoulli process: Data from a
      laboratory experiment.
AB  - The data presented in this article are related to the research article entitled
      "Discrete Adjustment to a Changing Environment: Experimental Evidence" (Khaw et
      al., 2017) [1]. We present data from a laboratory experiment that asks subjects
      to forecast the outcome of a time-varying Bernoulli process. On a computer
      program, subjects draw rings with replacement from a virtual box containing green
      and red rings in an unknown proportion. Subjects provide their estimates of the
      probability of drawing a green ring. They are rewarded for their participation
      and for the accuracy of their estimates. The actual probability of drawing a
      green ring is initially drawn from a uniform distribution. It then changes
      intermittently throughout the session, and each subsequent probability is an
      independent draw from the uniform distribution. Each session involves 1000 ring
      draws. The dataset contains the values of the underlying probability, the
      sequence of ring draws that are realized, and the subjects' estimates and
      response times. The dataset contains the performance of 11 subjects who each
      completed 10 sessions over the course of several days.

PMID- 29062872
TI  - S-nitroso- and nitro- proteomes in the olive (Olea europaea L.) pollen.
      Predictive versus experimental data by nano-LC-MS.
AB  - The data presented here are related to the research article entitled "Generation
      of nitric oxide by olive (Olea europaea L.) pollen during in vitro germination
      and assessment of the S-nitroso- and nitro-proteomes by computational predictive
      methods" doi:10.1016/j.niox.2017.06.005 (Jimenez-Quesada et al., 2017) [1].
      Predicted cysteine S-nitrosylation and Tyr-nitration sites in proteins derived
      from a de novo assembled and annotated pollen transcriptome from olive tree (Olea
      europaea L.) were obtained after using well-established predictive tools in
      silico. Predictions were performed using both default and highly restrictive
      thresholds. Numerous gene products identified with these characteristics are
      listed here. An experimental validation of the data, consisting in nano-LC-MS
      (Liquid Chromatography-Mass Spectrometry) determination of olive pollen proteins
      after immunoprecipitation with antibodies to anti-S-nitrosoCys and anti-3-NT
      (NitroTyrosine) allowed identification of numerous proteins subjected to these
      two post-translational modifications, which are listed here together with
      information regarding their cross-presence among the predictions.

PMID- 29062873
TI  - The effect of reducing the incidence of gastrointestinal complications in
      patients treated with aspirin, referred to Imam Hospital, of Ahvaz, Iran.
AB  - This research contains data which were obtained during the analysis of treated
      patients with aspirin who were referred to Imam Hospital (Imam H) of Ahvaz, Iran;
      and the effect of this type of treatment (Helicobacter pylori eradicate (HPE)) on
      reducing the incidence of gastrointestinal complications. Studies have shown that
      taking aspirin in patients with Helicobacter pylori infection is associated with
      a decreasing risk of gastrointestinal bleeding (O'connor et al., 2013) [1]. In
      this study, 165 patients with positive helicobacter pylori infection test were
      chosen among those who were referred to Imam H. In this paper, the effects of
      sex, smoking, renal failer, diabetes, age, blood pressure and aspirin consumption
      have been studied (Fletcher et al., 2010) [2]. After completion of the
      observations and records of patient's medical records, the obtained coded data
      were fed into EXCELL. Data analysis was performed, using SPSS 16.

PMID- 29062874
TI  - Synthesis of 1,2-phenylenediamine capturing molecule for the detection of
      diacetyl.
AB  - Here we describe the design of 1,2-phenylenediamine capturing molecule and the
      synthesis steps necessary for its preparation. The designed 1,2-phenylenediamine
      derivative is able to capture diacetyl in solution, as shown by ESIMS, forming a
      chemical adduct, 1-4-quinoxaline. The methyl esters of diacetyl-adduct (DAA) and
      pentanedione-adduct (PDA) are incorporated to the lysines in BSA and the
      conjugate used for antibody screening and selection. In the research article is
      described an enzyme-linked immunosorbent assay developed to detect and quantify
      diacetyl in complex media.

PMID- 29062875
TI  - Ocular coherence tomography image data of the retinal laminar structure in a
      mouse model of oxygen-induced retinopathy.
AB  - The data presented in this article are related to the research paper entitled
      "Norrin treatment improves ganglion cell survival in an oxygen-induced model of
      retinal ischemia" (Dailey et al., 2017) [1] This article describes treatment with
      the human Norrin protein, an atypical Wnt-protein, to improve the survival of
      retinal ganglion cells in a murine model of Oxygen-Induced Retinopathy (OIR).
      That study utilized Optical coherence tomography (OCT) to visualize retinal
      layers at high resolution in vivo, and to quantify changes to nerve fiber layer
      thickness. Organization of the laminar structure of other retinal layers in this
      model in vivo, were not known because of uncertainties regarding potential
      artifacts during the processing of tissue for traditional histology. The OCT
      image data provided here shows researchers the retinal laminar structural
      features that exist in vivo in this popular mouse OIR model. Traditional H&E
      stained retinal tissue sections are also provided here for comparison.

PMID- 29062876
TI  - Draft genome of the brown-rot fungus Fomitopsis pinicola GR9-4.
AB  - Basidiomycete brown-rot fungi have a huge importance for wood decomposition and
      thus the global carbon cycle. Here, we present the genome sequence of Fomitopsis
      pinicola GR9-4 which represent different F. pinicola clade than the previously
      sequenced North American isolate FP-58527 SS1. The genome was sequenced by using
      a paired-end sequence library of Illumina and a 2.5k and 5k mate-pair library
      (ABI SOLiD). The final assembly adds up to a size of 45 Mb (including gaps
      between contigs), with a GC-content of 56%. The gene prediction resulted in
      13,888 gene models. The genome sequence will be used as a basis for understanding
      population genomics, genome-wide association studies and wood decay mechanisms of
      this brown-rot fungus.

PMID- 29062877
TI  - Location Matters in Defining T Cell-mediated Immunity in Response to Salmonella
      Typhi Vaccination.

PMID- 29062878
TI  - Lamin Deficiency in the Liver Sets the Stage for Nonalcoholic Steatohepatitis
      Development in Males.

PMID- 29062879
TI  - Heterogeneity of Hepatitis C Virus Particles and Their Evolution During
      Infection.

PMID- 29062880
TI  - Setting up a Lab: The Early Years.

PMID- 29062881
TI  - Early Diagnosis of Gastroesophageal Cancers and the Cytosponge: A Work in
      Progress.

PMID- 29062882
TI  - Primary choriocarcinoma in postmenopausal women: Two case reports and review of
      the Texas Cancer Registry.
AB  - *We report on the medical treatment and outcomes of choriocarcinoma in Hispanic
      postmenopausal women.*A diagnosis of choriocarcinoma should be considered in
      older women with elevated serum beta-hCG levels.*The unadjusted incidence of
      choriocarcinoma was calculated using data from the Texas Cancer Registry.

PMID- 29062883
TI  - High-dose chemotherapy and stem-cell rescue for salvage therapy for relapsed
      malignant mixed ovarian germ cell tumor: A case report.
AB  - BACKGROUND: Malignant ovarian germ cell tumors are rare, and often treatable with
      surgery and chemotherapy. Few data are available for treatment of platinum
      resistant tumors. CASE: A 31 year old gravida 0 with a 20 cm pelvic mass was
      found to have a malignant ovarian germ cell tumor after she underwent debulking
      surgery. She initially responded to chemotherapy; however her AFP began to rise
      before all cycles were completed. She underwent additional debulking surgery that
      was again suboptimal. She was then referred for salvage therapy with high-dose
      chemotherapy with stem cell transplant, which was successful and she has had no
      evidence of disease for over two years. CONCLUSION: High-dose chemotherapy with
      stem cell transplant is a viable salvage therapy for patients with platinum
      resistant germ cell tumors.

PMID- 29062884
TI  - Norethindrone substituted for megestrol in the treatment of metastatic
      endometrial carcinoma: Three cases.
AB  - *Progestins can produce clinical benefit in a subset of women with metastatic
      endometrial cancer.*Corticosteroid-related effects of megestrol can cause
      morbidity over the long term.*Norethindrone is a progestin without corticosteroid
      side effects.*A switch from megestrol to norethindrone decreased toxicity with
      continued benefit.*A clinical trial of norethindrone for this population of
      patients would be welcome.

PMID- 29062885
TI  - Arctigenin inhibits prostate tumor cell growth in vitro and in vivo.
AB  - The low bioavailability of most phytochemicals limits their translation to
      humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from
      the seeds of Arctium lappa, has favorable bioavailability/potency against
      prostate cancer. The anticarcinogenic activity of arctigenin was investigated
      both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer
      cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse
      models. Arctigenin at lower doses (< 2MUM) significantly inhibited the
      proliferation of LNCaP and LAPC-4 cells by 30-50% at 48h compared to control, and
      inhibited WPE1-NA22 cells by 75%, while did not affect normal prostate epithelial
      cells. Male severe combined immunodeficiency (SCID) mice were implanted
      subcutaneously with LAPC-4 cells for in vivo studies. In one experiment, the
      intervention started one week after tumor implantation. Mice received arctigenin
      at 50mg/kg (LD) or 100mg/kg (HD) b.w. daily or vehicle control by oral gavage.
      After 6 weeks, tumor growth was inhibited by 50% (LD) and 70% (HD) compared to
      control. A stronger tumor inhibitory effect was observed in a second experiment
      where arctigenin intervention started two weeks prior to tumor implantation. Arc
      was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 MUM
      in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker
      Ki67, total and nuclear androgen receptor, and growth factors including VEGF,
      EGF, and FGF-beta were significantly decreased by Arc, along with an increase in
      apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were
      identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and
      miR-21-5p. This study provides the first in vivo evidence of the strong
      anticancer activity of arctigenin in prostate cancer. The effective dose of
      arctigenin in vitro is physiologically achievable in vivo, which provides a high
      promise in its translation to human application.

PMID- 29062886
TI  - Activating Peripheral Innate Immunity Enables Safe and Effective Oncolytic
      Virotherapy in the Brain.
AB  - The oncolytic mutant vesicular stomatitis virus VSVDelta51 achieves robust
      efficacy in multiple extracranial tumor models. Yet for malignancies of the
      brain, direct intratumoral infusion of VSVDelta51 causes lethal virus-induced
      neuropathology. Here, we have developed a novel therapeutic regime that uses
      peripheral immunization with a single sub-lethal dose of VSVDelta51 to establish
      an acute anti-viral state that enables the safe intracranial (IC) infusion of an
      otherwise lethal dose of VSVDelta51 within just 6 hr. Although type I interferons
      alone appeared insufficient to explain this protective phenotype, serum isolated
      at early time points from primed animals conferred protection against an IC dose
      of virus. Adaptive immune populations had minimal contributions. Finally, the
      therapeutic utility of this novel strategy was demonstrated by peripherally
      priming and intracranially treating mice bearing aggressive CT2A syngeneic
      astrocytomas with VSVDelta51. Approximately 25% of animals achieved complete
      regression of established tumors, with no signs of virus-induced neurological
      impairment. This approach may harness an early warning system in the brain that
      has evolved to protect the host against otherwise lethal neurotropic viral
      infections. We have exploited this protective mechanism to safely and
      efficaciously treat brain tumors with an otherwise neurotoxic virus, potentially
      widening the available treatment options for oncolytic virotherapy in the brain.

PMID- 29062888
TI  - Jamming and overpacking fuzzy microgels: Deformation, interpenetration, and
      compression.
AB  - Tuning the solubility of fuzzy polymer microgels by external triggers, such as
      temperature or pH, provides a unique mechanism for controlling the porosity and
      size of colloidal particles on the nanoscale. As a consequence, these smart
      microgel particles are being considered for applications ranging from viscosity
      modifiers and sensing to drug delivery and as models for the glass and the
      jamming transition. Despite their widespread use, little is known about how these
      soft particles adapt their shape and size under strong mechanical compression. We
      use a combination of precise labeling protocols and two-color superresolution
      microscopy to unravel the behavior of tracer microgels inside densely packed soft
      solids. We find that interpenetration and shape deformation are dominant until,
      in the highly overpacked state, this mechanism saturates and the only remaining
      way to further densify the system is by isotropic compression.

PMID- 29062887
TI  - Neuronal Intrinsic Physiology Changes During Development of a Learned Behavior.
AB  - Juvenile male zebra finches learn their songs over distinct auditory and
      sensorimotor stages, the former requiring exposure to an adult tutor song
      pattern. The cortical premotor nucleus HVC (acronym is name) plays a necessary
      role in both learning stages, as well as the production of adult song. Consistent
      with neural network models where synaptic plasticity mediates developmental forms
      of learning, exposure to tutor song drives changes in the turnover, density, and
      morphology of HVC synapses during vocal development. A network's output, however,
      is also influenced by the intrinsic properties (e.g., ion channels) of the
      component neurons, which could change over development. Here, we use patch clamp
      recordings to show cell-type-specific changes in the intrinsic physiology of HVC
      projection neurons as a function of vocal development. Developmental changes in
      HVC neurons that project to the basal ganglia include an increased voltage sag
      response to hyperpolarizing currents and an increased rebound depolarization
      following hyperpolarization. Developmental changes in HVC neurons that project to
      vocal-motor cortex include a decreased resting membrane potential and an
      increased spike amplitude. HVC interneurons, however, show a relatively stable
      range of intrinsic features across vocal development. We used mathematical models
      to deduce possible changes in ionic currents that underlie the physiological
      changes and to show that the magnitude of the observed changes could alter HVC
      circuit function. The results demonstrate developmental plasticity in the
      intrinsic physiology of HVC projection neurons and suggest that intrinsic
      plasticity may have a role in the process of song learning.

PMID- 29062889
TI  - Fault-tolerant quantum error detection.
AB  - Quantum computers will eventually reach a size at which quantum error correction
      becomes imperative. Quantum information can be protected from qubit imperfections
      and flawed control operations by encoding a single logical qubit in multiple
      physical qubits. This redundancy allows the extraction of error syndromes and the
      subsequent detection or correction of errors without destroying the logical state
      itself through direct measurement. We show the encoding and syndrome measurement
      of a fault-tolerantly prepared logical qubit via an error detection protocol on
      four physical qubits, represented by trapped atomic ions. This demonstrates the
      robustness of a logical qubit to imperfections in the very operations used to
      encode it. The advantage persists in the face of large added error rates and
      experimental calibration errors.

PMID- 29062890
TI  - Electrically driven monolithic subwavelength plasmonic interconnect circuits.
AB  - In the post-Moore era, an electrically driven monolithic optoelectronic
      integrated circuit (OEIC) fabricated from a single material is pursued globally
      to enable the construction of wafer-scale compact computing systems with powerful
      processing capabilities and low-power consumption. We report a monolithic
      plasmonic interconnect circuit (PIC) consisting of a photovoltaic (PV) cascading
      detector, Au-strip waveguides, and electrically driven surface plasmon polariton
      (SPP) sources. These components are fabricated from carbon nanotubes (CNTs) via a
      CMOS (complementary metal-oxide semiconductor)-compatible doping-free technique
      in the same feature size, which can be reduced to deep-subwavelength scale
      (~lambda/7 to lambda/95, lambda = 1340 nm) compared with the 14-nm technique
      node. An OEIC could potentially be configured as a repeater for data transport
      because of its "photovoltaic" operation mode to transform SPP energy directly
      into electricity to drive subsequent electronic circuits. Moreover, chip-scale
      throughput capability has also been demonstrated by fabricating a 20 * 20 PIC
      array on a 10 mm * 10 mm wafer. Tailoring photonics for monolithic integration
      with electronics beyond the diffraction limit opens a new era of chip-level
      nanoscale electronic-photonic systems, introducing a new path to innovate toward
      much faster, smaller, and cheaper computing frameworks.

PMID- 29062891
TI  - The landscape of transcription errors in eukaryotic cells.
AB  - Accurate transcription is required for the faithful expression of genetic
      information. To understand the molecular mechanisms that control the fidelity of
      transcription, we used novel sequencing technology to provide the first
      comprehensive analysis of the fidelity of transcription in eukaryotic cells. Our
      results demonstrate that transcription errors can occur in any gene, at any
      location, and affect every aspect of protein structure and function. In addition,
      we show that multiple proteins safeguard the fidelity of transcription and
      provide evidence suggesting that errors that evade these layers of RNA quality
      control profoundly affect the physiology of living cells. Together, these
      observations demonstrate that there is an inherent limit to the faithful
      expression of the genome and suggest that the impact of mutagenesis on cellular
      health and fitness is substantially greater than currently appreciated.

PMID- 29062893
TI  - Electrotunable artificial molecules based on van der Waals heterostructures.
AB  - Quantum confinement has made it possible to detect and manipulate single-electron
      charge and spin states. The recent focus on two-dimensional (2D) materials has
      attracted significant interests on possible applications to quantum devices,
      including detecting and manipulating either single-electron charging behavior or
      spin and valley degrees of freedom. However, the most popular model systems,
      consisting of tunable double-quantum-dot molecules, are still extremely difficult
      to realize in these materials. We show that an artificial molecule can be
      reversibly formed in atomically thin MoS2 sandwiched in hexagonal boron nitride,
      with each artificial atom controlled separately by electrostatic gating. The
      extracted values for coupling energies at different regimes indicate a single
      electron transport behavior, with the coupling strength between the quantum dots
      tuned monotonically. Moreover, in the low-density regime, we observe a decrease
      of the conductance with magnetic field, suggesting the observation of Coulomb
      blockade weak anti-localization. Our experiments demonstrate for the first time
      the realization of an artificial quantum-dot molecule in a gated MoS2 van der
      Waals heterostructure, which could be used to investigate spin-valley physics.
      The compatibility with large-scale production, gate controllability, electron
      hole bipolarity, and new quantum degrees of freedom in the family of 2D materials
      opens new possibilities for quantum electronics and its applications.

PMID- 29062892
TI  - Defect passivation of transition metal dichalcogenides via a charge transfer van
      der Waals interface.
AB  - Integration of transition metal dichalcogenides (TMDs) into next-generation
      semiconductor platforms has been limited due to a lack of effective passivation
      techniques for defects in TMDs. The formation of an organic-inorganic van der
      Waals interface between a monolayer (ML) of titanyl phthalocyanine (TiOPc) and a
      ML of MoS2 is investigated as a defect passivation method. A strong negative
      charge transfer from MoS2 to TiOPc molecules is observed in scanning tunneling
      microscopy. As a result of the formation of a van der Waals interface, the
      ION/IOFF in back-gated MoS2 transistors increases by more than two orders of
      magnitude, whereas the degradation in the photoluminescence signal is suppressed.
      Density functional theory modeling reveals a van der Waals interaction that
      allows sufficient charge transfer to remove defect states in MoS2. The present
      organic-TMD interface is a model system to control the surface/interface states
      in TMDs by using charge transfer to a van der Waals bonded complex.

PMID- 29062894
TI  - Transforming from planar to three-dimensional lithium with flowable interphase
      for solid lithium metal batteries.
AB  - Solid-state lithium (Li) metal batteries are prominent among next-generation
      energy storage technologies due to their significantly high energy density and
      reduced safety risks. Previously, solid electrolytes have been intensively
      studied and several materials with high ionic conductivity have been identified.
      However, there are still at least three obstacles before making the Li metal foil
      based solid-state systems viable, namely, high interfacial resistance at the
      Li/electrolyte interface, low areal capacity, and poor power output. The problems
      are addressed by incorporating a flowable interfacial layer and three-dimensional
      Li into the system. The flowable interfacial layer can accommodate the
      interfacial fluctuation and guarantee excellent adhesion at all time, whereas the
      three-dimensional Li significantly reduces the interfacial fluctuation from the
      whole electrode level (tens of micrometers) to local scale (submicrometer) and
      also decreases the effective current density for high-capacity and high-power
      operations. As a consequence, both symmetric and full-cell configurations can
      achieve greatly improved electrochemical performances in comparison to the
      conventional Li foil, which are among the best reported values in the literature.
      Noticeably, solid-state full cells paired with high-mass loading LiFePO4
      exhibited, at 80 degrees C, a satisfactory specific capacity even at a rate of 5
      C (110 mA.hour g-1) and a capacity retention of 93.6% after 300 cycles at a
      current density of 3 mA cm-2 using a composite solid electrolyte middle layer. In
      addition, when a ceramic electrolyte middle layer was adopted, stable cycling
      with greatly improved capacity could even be realized at room temperature.

PMID- 29062896
TI  - Copper Chaperone CupA and Zinc Control CopY Regulation of the Pneumococcal cop
      Operon.
AB  - Any metal in excess can be toxic; therefore, metal homeostasis is critical to
      bacterial survival. Bacteria have developed specialized metal import and export
      systems for this purpose. For broadly toxic metals such as copper, bacteria have
      evolved only export systems. The copper export system (cop operon) usually
      consists of the operon repressor, the copper chaperone, and the copper exporter.
      In Streptococcus pneumoniae, the causative agent of pneumonia, otitis media,
      sepsis, and meningitis, little is known about operon regulation. This is partly
      due to the S. pneumoniae repressor, CopY, and copper chaperone, CupA, sharing
      limited homology to proteins of putative related function and confirmed
      established systems. In this study, we examined CopY metal crosstalk, CopY
      interactions with CupA, and how CupA can control the oxidation state of copper.
      We found that CopY bound zinc and increased the DNA-binding affinity of CopY by
      roughly an order of magnitude over that of the apo form of CopY. Once copper
      displaced zinc in CopY, resulting in operon activation, CupA chelated copper from
      CopY. After copper was acquired from CopY or other sources, if needed, CupA
      facilitated the reduction of Cu2+ to Cu1+, which is the exported copper state.
      Taken together, these data show novel mechanisms for copper processing in S.
      pneumoniae. IMPORTANCE As mechanisms of copper toxicity are emerging, bacterial
      processing of intracellular copper, specifically inside Streptococcus pneumoniae,
      remains unclear. In this study, we investigated two proteins encoded by the
      copper export operon: the repressor, CopY, and the copper chaperone, CupA. Zinc
      suppressed transcription of the copper export operon by increasing the affinity
      of CopY for DNA. Furthermore, CupA was able to chelate copper from CopY not bound
      to DNA and reduce it from Cu2+ to Cu1+. This reduced copper state is essential
      for bacterial copper export via CopA. In view of the fact that innate immune
      cells use copper to kill pathogenic bacteria, understanding the mechanisms of
      copper export could expose new small-molecule therapeutic targets that could work
      synergistically with copper against pathogenic bacteria.

PMID- 29062895
TI  - Norovirus Escape from Broadly Neutralizing Antibodies Is Limited to Allostery
      Like Mechanisms.
AB  - Ideal antiviral vaccines elicit antibodies (Abs) with broad strain recognition
      that bind to regions that are difficult to mutate for escape. Using 10 murine
      norovirus (MNV) strains and 5 human norovirus (HuNoV) virus-like particles
      (VLPs), we identified monoclonal antibody (MAb) 2D3, which broadly neutralized
      all MNV strains tested. Importantly, escape mutants corresponding to this
      antibody were very slow to develop and were distal to those raised against our
      previously studied antibody, A6.2. To understand the atomic details of 2D3
      neutralization, we determined the cryo-electron microscopy (cryo-EM) structure of
      the 2D3/MNV1 complex. Interestingly, 2D3 binds to the top of the P domain, very
      close to where A6.2 binds, but the only escape mutations identified to date fall
      well outside the contact regions of both 2D3 and A6.2. To determine how mutations
      in distal residues could block antibody binding, we used molecular dynamics
      flexible fitting simulations of the atomic structures placed into the density map
      to examine the 2D3/MNV1 complex and these mutations. Our findings suggest that
      the escape mutant, V339I, may stabilize a salt bridge network at the P-domain
      dimer interface that, in an allostery-like manner, affects the conformational
      relaxation of the P domain and the efficiency of binding. They further highlight
      the unusual antigenic surface bound by MAb 2D3, one which elicits cross-reactive
      antibodies but which the virus is unable to alter to escape neutralization. These
      results may be leveraged to generate norovirus (NoV) vaccines containing broadly
      neutralizing antibodies. IMPORTANCE The simplest and most common way for viruses
      to escape antibody neutralization is by mutating residues that are essential for
      antibody binding. Escape mutations are strongly selected for by their effect on
      viral fitness, which is most often related to issues of protein folding, particle
      assembly, and capsid function. The studies presented here demonstrated that a
      broadly neutralizing antibody to mouse norovirus binds to an exposed surface but
      that the only escape mutants that arose were distal to the antibody binding
      surface. To understand this finding, we performed an in silico analysis that
      suggested that those escape mutations blocked antibody binding by affecting
      structural plasticity. This kind of antigenic region-one that gives rise to
      broadly neutralizing antibodies but that the virus finds difficult to escape from
      is therefore ideal for vaccine development.

PMID- 29062897
TI  - Synergistic Activity between Two Antifungal Proteins, the Plant Defensin NaD1 and
      the Bovine Pancreatic Trypsin Inhibitor.
AB  - Defensins are a large family of small, cationic, cysteine-rich proteins that are
      part of the defense arsenal that plants use for protection against potentially
      damaging fungal infections. The plant defensin NaD1 from Nicotiana alata is a
      potent antifungal protein that inhibits growth and kills a variety of fungal
      pathogens that affect both plant and animal (human) hosts. Some serine protease
      inhibitors have also been reported to be antifungal molecules, while others have
      no inhibitory activity against fungi. Here we describe the synergistic activity
      of the plant defensin NaD1 with a selection of serine protease inhibitors against
      the plant pathogens Fusarium graminearum and Colletotrichum graminicola and the
      animal pathogen Candida albicans. The synergistic activity was not related to the
      protease inhibitory activity of these molecules but may arise from activation of
      fungal stress response pathways. The bovine pancreatic trypsin inhibitor (BPTI)
      displayed the most synergy with NaD1. BPTI also acted synergistically with
      several other antifungal molecules. The observation that NaD1 acts
      synergistically with protease inhibitors provides the foundation for the design
      of transgenic plants with improved resistance to fungal disease. It also supports
      the possibility of naturally occurring accessory factors that function to enhance
      the activity of innate immunity peptides in biological systems. IMPORTANCE This
      work describes the increased activity of a natural antifungal peptide in the
      presence of another antifungal peptide from a different family. This is termed
      antifungal synergy. Synergy is important for decreasing the amount of antifungal
      molecule needed to control the disease. Traditionally, naturally occurring
      antifungal molecules are assayed in isolation. Identification of synergistic
      interactions between antifungal peptides means that their activities in a complex
      biological system are likely to be different from what we observe when examining
      them individually. This study identified synergy between an antifungal peptide
      and a group of peptides that do not affect fungal growth in vitro. This provides
      the foundation for generation of transgenic plants with increased resistance to
      fungal disease and identification of antifungal accessory factors that enhance
      the activity of innate immune molecules but do not have an antifungal effect on
      their own.

PMID- 29062898
TI  - Essential Assembly Factor Rpf2 Forms Novel Interactions within the 5S RNP in
      Trypanosoma brucei.
AB  - Ribosome biogenesis is a highly complex and conserved cellular process that is
      responsible for making ribosomes. During this process, there are several assembly
      steps that function as regulators to ensure proper ribosome formation. One of
      these steps is the assembly of the 5S ribonucleoprotein particle (5S RNP) in the
      central protuberance of the 60S ribosomal subunit. In eukaryotes, the 5S RNP is
      composed of 5S rRNA, ribosomal proteins L5 and L11, and assembly factors Rpf2 and
      Rrs1. Our laboratory previously showed that in Trypanosoma brucei, the 5S RNP is
      composed of 5S rRNA, L5, and trypanosome-specific RNA binding proteins P34 and
      P37. In this study, we characterize an additional component of the 5S RNP, the T.
      brucei homolog of Rpf2. This is the first study to functionally characterize
      interactions mediated by Rpf2 in an organism other than fungi. T. brucei Rpf2
      (TbRpf2) was identified from tandem affinity purification using extracts prepared
      from protein A-tobacco etch virus (TEV)-protein C (PTP)-tagged L5, P34, and P37
      cell lines, followed by mass spectrometry analysis. We characterized the binding
      interactions between TbRpf2 and the previously characterized members of the T.
      brucei 5S RNP. Our studies show that TbRpf2 mediates conserved binding
      interactions with 5S rRNA and L5 and that TbRpf2 also interacts with trypanosome
      specific proteins P34 and P37. We performed RNA interference (RNAi) knockdown of
      TbRpf2 and showed that this protein is essential for the survival of the
      parasites and is critical for proper ribosome formation. These studies provide
      new insights into a critical checkpoint in the ribosome biogenesis pathway in T.
      brucei. IMPORTANCETrypanosoma brucei is the parasitic protozoan that causes
      African sleeping sickness. Ribosome assembly is essential for the survival of
      this parasite through the different host environments it encounters during its
      life cycle. The assembly of the 5S ribonucleoprotein particle (5S RNP) functions
      as one of the regulatory checkpoints during ribosome biogenesis. We have
      previously characterized the 5S RNP in T. brucei and showed that trypanosome
      specific proteins P34 and P37 are part of this complex. In this study, we
      characterize for the first time the interactions of the homolog of the assembly
      factor Rpf2 with members of the 5S RNP in another organism besides fungi. Our
      studies show that Rpf2 is essential in T. brucei and that it forms unique
      interactions within the 5S RNP, particularly with P34 and P37. These studies have
      identified parasite-specific interactions that can potentially function as new
      therapeutic targets against sleeping sickness.

PMID- 29062899
TI  - Differential Roles for Inner Membrane Complex Proteins across Toxoplasma gondii
      and Sarcocystis neurona Development.
AB  - The inner membrane complex (IMC) of apicomplexan parasites contains a network of
      intermediate filament-like proteins. The 14 alveolin domain-containing IMC
      proteins in Toxoplasma gondii fall into different groups defined by their
      distinct spatiotemporal dynamics during the internal budding process of
      tachyzoites. Here, we analyzed representatives of different IMC protein groups
      across all stages of the Toxoplasma life cycle and during Sarcocystis neurona
      asexual development. We found that across asexually dividing Toxoplasma stages,
      IMC7 is present exclusively in the mother's cytoskeleton, whereas IMC1 and IMC3
      are both present in mother and daughter cytoskeletons (IMC3 is strongly enriched
      in daughter buds). In developing macro- and microgametocytes, IMC1 and -3 are
      absent, whereas IMC7 is lost in early microgametocytes but retained in
      macrogametocytes until late in their development. We found no roles for IMC
      proteins during meiosis and sporoblast formation. However, we observed that IMC1
      and IMC3, but not IMC7, are present in sporozoites. Although the spatiotemporal
      pattern of IMC15 and IMC3 suggests orthologous functions in Sarcocystis, IMC7 may
      have functionally diverged in Sarcocystis merozoites. To functionally
      characterize IMC proteins, we knocked out IMC7, -12, -14, and -15 in Toxoplasma.
      IMC14 and -15 appear to be involved in switching between endodyogeny and
      endopolygeny. In addition, IMC7, -12, and -14, which are all recruited to the
      cytoskeleton outside cytokinesis, are critical for the structural integrity of
      extracellular tachyzoites. Altogether, stage- and development-specific roles for
      IMC proteins can be discerned, suggesting different niches for each IMC protein
      across the entire life cycle. IMPORTANCE The inner membrane complex (IMC) is a
      defining feature of apicomplexan parasites key to both their motility and unique
      cell division. To provide further insights into the IMC, we analyzed the dynamics
      and functions of representative alveolin domain-containing IMC proteins across
      developmental stages. Our work shows universal but distinct roles for IMC1, -3,
      and -7 during Toxoplasma asexual division but more specialized functions for
      these proteins during gametogenesis. In addition, we find that IMC15 is involved
      in daughter formation in both Toxoplasma and Sarcocystis. IMC14 and IMC15
      function in limiting the number of Toxoplasma offspring per division.
      Furthermore, IMC7, -12, and -14, which are recruited in the G1 cell cycle stage,
      are required for stress resistance of extracellular tachyzoites. Thus, although
      the roles of the different IMC proteins appear to overlap, stage- and development
      specific behaviors indicate that their functions are uniquely tailored to each
      life stage requirement.

PMID- 29062900
TI  - Microbiota Diversification and Crash Induced by Dietary Oxalate in the Mammalian
      Herbivore Neotoma albigula.
AB  - Oxalate, broadly found in both dietary and endogenous sources, is a primary
      constituent in 80% of kidney stones, an affliction that has tripled in prevalence
      over the last 40 years. Oxalate-degrading bacteria within the gut microbiota can
      mitigate the effects of oxalate and are negatively correlated with kidney stone
      formation, but bacteriotherapies involving oxalate-degrading bacteria have met
      with mixed results. To inform the development of more effective and consistent
      bacteriotherapies, we sought to quantify the interactions and limits between
      oxalate and an oxalate-adapted microbiota from the wild mammalian herbivore
      Neotoma albigula (woodrat), which consumes a high-oxalate diet in the wild. We
      tracked the microbiota over a variable-oxalate diet ranging from 0.2% to 12%,
      with the upper limit approximating 10* the level of human consumption. The N.
      albigula microbiota was capable of degrading ~100% of dietary oxalate regardless
      of the amount consumed. However, the microbiota exhibited significant changes in
      diversity dynamically at the operational taxonomic unit (OTU), family, and
      community levels in accordance with oxalate input. Furthermore, a cohesive
      microbial network was stimulated by the consumption of oxalate and exhibited some
      resistance to the effects of prolonged exposure. This study demonstrates that the
      oxalate-adapted microbiota of N. albigula exhibits a very high level of
      degradation and tolerance for oxalate. IMPORTANCE The bacteria associated with
      mammalian hosts exhibit extensive interactions with overall host physiology and
      contribute significantly to the health of the host. Bacteria are vital to the
      mitigation of the toxic effects of oxalate specifically as mammals do not possess
      the enzymes to degrade this compound, which is present in the majority of kidney
      stones. Contrary to the body of literature on a few oxalate-degrading
      specialists, our work illustrates that oxalate stimulates a broad but cohesive
      microbial network in a dose-dependent manner. The unique characteristics of the
      N. albigula microbiota make it an excellent source for the development of
      bacteriotherapies to inhibit kidney stone formation. Furthermore, this work
      successfully demonstrates methods to identify microbial networks responsive to
      specific toxins, their limits, and important elements such as microbial network
      cohesivity and architecture. These are necessary steps in the development of
      targeted bacteriotherapies.

PMID- 29062901
TI  - New directions in hepatitis B therapy research.
AB  - Chronic hepatitis B treatment is available for a long period, allowing disease
      control and infection suppression, but it is rarely responsible for HBsAg
      clearance. None of the drugs available aim at cccDNA, the obstacle in HBV
      infection eradication. Complications related to CHB, such as liver insufficiency,
      cirrhosis, and hepatocellular carcinoma are reduced in conditions of good viremia
      suppression, but still exist even after HBsAg seroclearance, what makes a need
      for urgent forthcoming of new therapeutics. Recent years brought promising and
      interesting results of experimental approaches, which are directed against
      different phases of HBV life cycle, target ccc DNA, or boost, and restore host
      immune response. Unfortunately, encouraging results in vitro and on animal models
      are not always reflected in human. Nevertheless, the multiplicity of novel
      antivirals allows to expect that at least some of them will enter clinical
      practice and relieve patients from chronic hepatitis B, fatal and devastating
      disease.

PMID- 29062902
TI  - The interplay between Th17 and T-regulatory responses as well as adipokines in
      the progression of non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disease,
      coupled with metabolic syndrome, which may progress to non-alcoholic
      steatohepatitis (NASH). Diabetes, obesity, hypertension, hypercholesterolemia,
      and hypertriglyceridemia are considered to be the most common causes leading to
      the incidence of NAFLD. It is assumed that the accumulation of lipid deposits in
      hepatocytes leads to production of proinflammatory cytokines that triggers the
      development of liver inflammation. Regulatory T cells (Tregs) play a critical
      role in regulating inflammatory processes in NASH, while T helper type 17 (Th17)
      might functionally oppose Treg-mediated responses. In addition, important
      mediators of hepatic steatosis are fatty hormones known as adipokines. We aimed
      to describe the significance and interaction between Treg and Th17-related
      cytokines as well as adipokines in pathogenesis and its potential use as
      biomarkers of NAFLD, especially with respect to progression to NASH.

PMID- 29062903
TI  - The risk of complications of endoscopic procedures in patients with liver
      cirrhosis.
AB  - Endoscopy methods involve diagnostics as well as therapy. Endoscopic techniques
      have a small but definite incidence of complication, so endoscopy should not be
      performed routinely but only on the basis of indication. The typical endoscopic
      procedures used in diagnostics and therapy of liver cirrhosis are endoscopy of
      upper and lower gastrointestinal tract. Other techniques are less common.
      Significance of endoscopy procedures increases in case of chronic progressive
      liver diseases, independently of etiology, where changes in gastrointestinal
      tract are observed in 87% of patients.

PMID- 29062905
TI  - The impact of the recipient and donor interferon lambda-3 polymorphism on the
      course of HCV infection following liver transplantation.
AB  - AIM OF THE STUDY: Aim of the study was to assess the impact of the recipient and
      donor interferon lambda-3 (IFNL3) single-nucleotide polymorphisms (SNPs)
      rs12979860 and rs8099917 on the course of hepatitis C virus (HCV) reinfection
      following liver transplantation. MATERIAL AND METHODS: The study involved 141
      subjects after liver transplantation for HCV-induced cirrhosis, performed between
      2000 and 2015. It assessed the impact of both SNPs on the outcomes of
      interferon/ribavirin (IFN/RBV) treatment following transplantation, HCV viral
      load, laboratory test results, histological lesions in the liver graft, the risk
      of acute rejection, and the development of hepatocellular carcinoma (HCC) in
      patient's own liver. RESULTS: In the case of rs12979860, SVR was achieved in
      58.8% of recipients with the CC genotype, and only 12% of recipients with the TT
      genotype (p = 0.016). Recipients with the rs12979860 CC variant had lower viral
      load and lower alanine transaminase (ALT) activity than recipients with a non-CC
      variant. Opposite effects were demonstrated in the analysis of the donors'
      genotype. Recipients with the unfavorable variants (rs12979860 TT and rs8099917
      GG) had a lower risk of graft rejection and tended to have a higher risk of
      developing HCC in their own liver. CONCLUSIONS: The IFNL3 rs12979860 polymorphism
      may be considered a predictor for IFN/RBV effectiveness following liver
      transplantation. The course of HCV reinfection following liver transplantation
      may be more aggressive if an unfavorable variant in the recipient coexists with a
      promising variant in the donor. Particularly careful monitoring for HCC in
      recipients with unfavorable IFNL3 variants is warranted.

PMID- 29062904
TI  - Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in
      isolated brain and liver mitochondria, and the effect of taurine administration:
      relevance to hepatic encephalopathy treatment.
AB  - INTRODUCTION: Ammonia-induced oxidative stress, mitochondrial dysfunction, and
      energy crisis are known as some the major mechanisms of brain injury in hepatic
      encephalopathy (HE). Hyperammonemia also affects the liver and hepatocytes.
      Therefore, targeting mitochondria seems to be a therapeutic point of intervention
      in the treatment of HE. Taurine is an abundant amino acid in the human body.
      Several biological functions including the mitochondrial protective properties
      are attributed to this amino acid. The aim of this study is to evaluate the
      effect of taurine administration on ammonia-induced mitochondrial dysfunction.
      MATERIAL AND METHODS: Isolated mice liver and brain mitochondria were exposed to
      different concentrations of ammonia (1, 5, 10, and 20 mM) and taurine (1, 5, and
      10 mM), and several mitochondrial indices were assessed. RESULTS: It was found
      that ammonia inhibited mitochondrial dehydrogenases activity caused collapse of
      mitochondrial membrane potential (MMP), induced mitochondrial swelling (MPP), and
      increased reactive oxygen species (ROS) in isolated liver and brain mitochondria.
      Furthermore, a significant amount of lipid peroxidation (LPO), along with
      glutathione (GSH) and ATP depletion, was detected in ammonia exposed
      mitochondria. Taurine administration (5 and 10 mM) mitigated ammonia-induced
      mitochondrial dysfunction. CONCLUSIONS: The current investigation demonstrates
      that taurine is instrumental in preserving brain and liver mitochondrial function
      in a hyperammonemic environment. The data suggest taurine as a potential
      protective agent with a therapeutic capability against hepatic encephalopathy and
      hyperammonemia.

PMID- 29062906
TI  - Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic
      children?
AB  - AIM OF THE STUDY: To assess if elevated serum cystatin C (Cyst-C) is an indicator
      for renal or hepatic dysfunction in presence of liver fibrosis. MATERIAL AND
      METHODS: Data of 50 children with chronic liver diseases (CLDs), out of which 25
      were without renal impairment, and 25 with renal impairment were analyzed. Twenty
      healthy children served as a healthy control group. Routine investigations,
      creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and
      liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C
      concentration by particle induced immunonephelometry were completed for both
      patients and control group. RESULTS: Results showed that serum Cyst-C is not
      correlated with the degree of hepatic impairment (p > 0.05). Cyst-C levels were
      significantly higher in patients with renal impairment (3.66 +/- 0.85) than those
      without (0.71 +/- 0.12), and healthy control group (0.63 +/- 0.85). Cystatin-C
      showed significant elevation in patients with severe fibrosis with renal
      impairment (3.66 +/- 0.85) than those without (0.76 +/- 0.04) (p < 0.0001). Cyst
      C at cutoff levels of 1.65 mg/l showed 100% accuracy in discrimination between
      those with and those without renal impairment. Cyst-C > 2.34 mg/l predicting GFR
      < 40 ml/min with accuracy of 90%. Cyst-C > 2.73 mg/l predicting GFR < 20 ml/min
      with accuracy of 81.5%. CONCLUSIONS: Serum Cyst-C is a promising marker to
      estimate renal impairment in children with CLDs. Further studies are needed to
      estimate the accuracy of serum Cyst-C for early detection of renal impairment and
      close monitoring of the hepatic children.

PMID- 29062907
TI  - Ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin for treatment of
      chronic hepatitis C 1 genotype in the Republic of Belarus.
AB  - AIM OF THE STUDY: Aim of the study is to evaluate real-world efficacy of the
      ombitasvir/ paritaprevir/ ritonavir + dasabuvir +/- ribavirin for treatment of
      chronic hepatitis C 1 genotype. MATERIAL AND METHODS: The study included 27
      patients according to inclusion criteria. Main laboratory studies were performed
      in all patients at the baseline and during the treatment. RESULTS: Efficacy of
      the antiviral therapy was assessed by measuring the SVR12 and the SVR24 along
      with measuring of viral load during the treatment. The SVR12 and SVR24 rate was
      100% (27/27). DISCUSSION: The results of the treatment were comparable to the
      results of pivotal, large-scale, randomized clinical trials. There were no
      serious adverse events during the treatment.

PMID- 29062908
TI  - Megamitochondria formation in hepatocytes of patient with chronic hepatitis C - a
      case report.
AB  - Although chronic hepatitis C virus (HCV) infection affect 185 million people
      world-wide, pathomechanism of liver damage is still unclear. Electron microscopy
      can reveal liver injury in very early stage and help understanding the mechanisms
      that is crucial in the pathogenesis of chronic hepatitis C. We present the
      morphological changes in the liver of HCV infected 24-year-old female patient,
      using light and transmission electron microscopy. Examination by TEM revealed
      wide range of specific subcellular abnormalities in hepatocellular
      ultrastructure. The most common observed changes were ring-shaped nuclei with
      intranuclear inclusion, megamitochondria, and "membranous web" structures - the
      hallmark of RNA-viruses infection.

PMID- 29062909
TI  - Congenital hepatic fibrosis in a 9-year-old female patient - a case report.
AB  - Congenital hepatic fibrosis (CHF) is a rare, autosomal recessive disorder,
      clinically characterized by hepatic fibrosis and portal hypertension. CHF results
      from ductal plate malformation (DPM) of the intrahepatic bile ducts. Four
      clinical forms can be observed: portal hypertensive, cholangitic, mixed and
      latent. CHF is one of the "fibropolycystic diseases" which also include several
      conditions with a variety of intrahepatic bile duct dilatation and associated
      periportal fibrosis such as Caroli disease, autosomal recessive and dominant
      polycystic kidney disease (ARPKD or ADPKD), Ivemark, Jeune, Joubert, Bardet
      Biedl, Meckel-Gruber and Arima syndromes. Most of them are accompanied by
      progressive cystic degeneration of the kidneys. We present the case of a 9-year
      old female patient with CHF with nonspecific clinical manifestation and a review
      of the literature.

PMID- 29062910
TI  - Inhibition of IRE1alpha-mediated XBP1 mRNA cleavage by XBP1 reveals a novel
      regulatory process during the unfolded protein response.
AB  - Background: The mammalian endoplasmic reticulum (ER) continuously adapts to the
      cellular secretory load by the activation of an unfolded protein response (UPR). 
      This stress response results in expansion of the ER, upregulation of proteins
      involved in protein folding and degradation, and attenuation of protein
      synthesis.  The response is orchestrated by three signalling pathways each
      activated by a specific signal transducer, either inositol requiring enzyme alpha
      (IRE1alpha), double-stranded RNA-activated protein kinase-like ER kinase (PERK)
      or activating transcription factor 6 (ATF6).  Activation of IRE1alpha results in
      its oligomerisation, autophosphorylation and stimulation of its ribonuclease
      activity.  The ribonuclease initiates the splicing of an intron from mRNA
      encoding the transcription factor, X-box binding protein 1 (XBP1), as well as
      degradation of specific mRNAs and microRNAs. Methods: To investigate the
      consequence of expression of exogenous XBP1, we generated a stable cell-line
      expressing spliced XBP1 mRNA under the control of an inducible promotor. Results:
      Following induction of expression, high levels of XBP1 protein were detected,
      which allowed upregulation of target genes in the absence of induction of the
      UPR.  Remarkably under stress conditions, the expression of exogenous XBP1
      repressed splicing of endogenous XBP1 mRNA without repressing the activation of
      PERK. Conclusions: These results illustrate that a feedback mechanism exists to
      attenuate Ire1alpha ribonuclease activity in the presence of XBP1.

PMID- 29062911
TI  - Using data from a multi-hospital clinical network to explore prevalence of
      pediatric rickets in Kenya.
AB  - Background: Nutritional rickets is a public health concern in developing
      countries despite tropical climates and a re-emerging issue in developed
      countries. In this study, we reviewed pediatric admission data from the Clinical
      Information Network (CIN) to help determine hospital and region based prevalence
      of rickets in three regions of Kenya (Central Kenya, Western Kenya and Nairobi
      County). We also examine the association of rickets with other diagnosis, such as
      malnutrition and pneumonia, and study the effect of rickets on regional hospital
      stays. Methods: We analyzed discharge records for children aged 1 month to 5
      years from county (formerly district) hospitals in the CIN, with admissions from
      February 1 st 2014 to February 28 th 2015. The strength of the association
      between rickets and key demographic factors, as well as with malnutrition and
      pneumonia, was assessed using odds ratios. The Fisher exact test was used to test
      the significance of the estimated odd ratios. Kaplan-Meier curves were used to
      analyze length of hospital stays. Results: There was a marked difference in
      prevalence across the three regions, with Nairobi having the highest number of
      cases of rickets at a proportion of 4.01%, followed by Central Region at 0.92%.
      Out of 9756 admissions in the Western Region, there was only one diagnosis of
      rickets. Malnutrition was associated with rickets; this association varied
      regionally. Pneumonia was found to be associated with rickets in Central Kenya.
      Children diagnosed with rickets had longer hospital stays, even when cases of
      malnutrition and pneumonia were excluded in the analysis. Conclusion: There was
      marked regional variation in hospital based prevalence of rickets, but in some
      regions it is a common clinical diagnosis suggesting the need for targeted public
      health interventions. Factors such as maternal and child nutrition, urbanization
      and cultural practices might explain these differences.

PMID- 29062912
TI  - Differential response of the liver to bile acid treatment in a mouse model of
      Niemann-Pick disease type C.
AB  - Niemann-Pick disease type C (NPC) disease is a neurodegenerative lysosomal
      storage disease caused by mutations in the NPC1 or NPC2 genes. Liver disease is
      also a common feature of NPC that can present as cholestatic jaundice in the
      neonatal period. Liver enzymes can remain elevated above the normal range in some
      patients as they age. We recently reported suppression of the P450 detoxification
      system in a mouse model of NPC disease and in post-mortem liver from NPC
      patients. As bile acids regulate the P450 system, we tested bile acid treatment
      using ursodeoxycholic acid (UDCA; 3alpha, 7beta-dihydroxy-5beta-cholanic acid), a
      hydrophilic bile acid, which is used to treat several cholestatic disorders. In
      this study, we compared UDCA treatment with the bile acid cholic acid (CA), and
      found unexpected hepatotoxicity in response to CA in Npc1 mice, but not to UDCA,
      suggesting that only UDCA should be used as an adjunctive therapy in NPC
      patients.

PMID- 29062913
TI  - Safety and effectiveness of mass drug administration to accelerate elimination of
      artemisinin-resistant falciparum malaria: A pilot trial in four villages of
      Eastern Myanmar.
AB  - Background: Artemisinin and partner drug-resistant falciparum malaria is
      expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum
      malaria in the GMS while drugs still retain enough efficacy could prevent global
      spread of antimalarial resistance. Eliminating malaria rapidly requires targeting
      the reservoir of asymptomatic parasite carriers. This pilot trial aimed to
      evaluate the acceptability, safety, feasibility and effectiveness of mass-drug
      administration (MDA) in reducing malaria in four villages in Eastern Myanmar.
      Methods: Villages with >=30% malaria prevalence were selected. Long-lasting
      insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment
      (EDT) were provided. Two villages received MDA immediately and two were followed
      for nine months pre-MDA. MDA consisted of a 3-day supervised course of 
      dihydroartemisinin-piperaquine and single low-dose primaquine administered
      monthly for three months. Adverse events (AE) were monitored by interviews and
      consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly
      for 24 months. Symptomatic malaria incidence,entomological indices, and
      antimalarial resistance markers were monitored. Results: MDA was well tolerated.
      There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931)
      interviews. In the smaller villages, participation to three MDA courses was 61%
      and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was
      higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus
      6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was
      lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014).
      After nine months the difference was no longer significant (2.0%(1.0-3.5) versus
      0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar
      between intervention and control. Before/after MDA comparisons showed that
      asymptomatic P. falciparum carriage and anopheline vector positivity decreased
      significantly whereas prevalence of the artemisinin-resistance molecular marker
      remained stable. Conclusions: This MDA was safe and feasible, and, could
      accelerate elimination of P. falciparum in addition to EDT and LLINs when
      community participation was sufficient.

PMID- 29062914
TI  - The integration site of the APP transgene in the J20 mouse model of Alzheimer's
      disease.
AB  - Background: Transgenic animal models are a widely used and powerful tool to
      investigate human disease and develop therapeutic interventions. Making a
      transgenic mouse involves random integration of exogenous DNA into the host
      genome that can have the effect of disrupting endogenous gene expression. The J20
      mouse model of Alzheimer's disease (AD) is a transgenic overexpresser of human
      APP with familial AD mutations and has been extensively utilised in preclinical
      studies and our aim was to determine the genomic location of the J20 transgene
      insertion. Methods: We used a combination of breeding strategy and Targeted Locus
      Amplification with deep sequencing to identify the insertion site of the J20
      transgene array. To assess RNA and protein expression of Zbtb20, we used qRT-PCR
      and Western Blotting. Results: We demonstrate that the J20 transgene construct
      has inserted within the genetic locus of endogenous mouse gene Zbtb20 on
      chromosome 16 in an array , disrupting expression of mRNA from this gene in adult
      hippocampal tissue, while expression of Zbtb20 protein remains unchanged. We note
      that the endogenous mouse App gene also lies on chromosome 16, although 42 Mb
      from the Zbtb20 locus. Conclusions: These data will be useful for future studies
      utilising this popular model of AD, particularly those investigating gene
      interactions between the J20 APP transgene and other genes present on Mmu16 in
      the mouse.

PMID- 29062915
TI  - Electronic health record and genome-wide genetic data in Generation Scotland
      participants.
AB  - This article provides the first detailed demonstration of the research value of
      the Electronic Health Record (EHR) linked to research data in Generation Scotland
      Scottish Family Health Study (GS:SFHS) participants, together with how to access
      this data. The structured, coded variables in the routine biochemistry,
      prescribing and morbidity records, in particular, represent highly valuable
      phenotypic data for a genomics research resource. Access to a wealth of other
      specialized datasets, including cancer, mental health and maternity inpatient
      information, is also possible through the same straightforward and transparent
      application process. The EHR linked dataset is a key component of GS:SFHS, a
      biobank conceived in 1999 for the purpose of studying the genetics of health
      areas of current and projected public health importance. Over 24,000 adults were
      recruited from 2006 to 2011, with broad and enduring written informed consent for
      biomedical research. Consent was obtained from 23,603 participants for GS:SFHS
      study data to be linked to their Scottish National Health Service (NHS) records,
      using their Community Health Index number. This identifying number is used for
      NHS Scotland procedures (registrations, attendances, samples, prescribing and
      investigations) and allows healthcare records for individuals to be linked across
      time and location. Here, we describe the NHS EHR dataset on the sub-cohort of
      20,032 GS:SFHS participants with consent and mechanism for record linkage plus
      extensive genetic data. Together with existing study phenotypes, including family
      history and environmental exposures, such as smoking, the EHR is a rich resource
      of real world data that can be used in research to characterise the health
      trajectory of participants, available at low cost and a high degree of
      timeliness, matched to DNA, urine and serum samples and genome-wide genetic
      information.

PMID- 29062916
TI  - A re-assessment of gene-tag classification approaches for describing var gene
      expression patterns during human Plasmodium falciparum malaria parasite
      infections.
AB  - PfEMP1 are variant parasite antigens that are inserted on the surface of
      Plasmodium falciparum infected erythrocytes (IE). Through interactions with
      various host molecules, PfEMP1 mediate IE sequestration in tissues and play a key
      role in the pathology of severe malaria. PfEMP1 is encoded by a diverse multi
      gene family called var. Previous studies have shown that that expression of
      specific subsets of var genes are associated with low levels of host immunity and
      severe malaria. However, in most clinical studies to date, full-length var gene
      sequences were unavailable and various approaches have been used to make
      comparisons between var gene expression profiles in different parasite isolates
      using limited information. Several studies have relied on the classification of a
      300 - 500 base-pair "DBLalpha tag" region in the DBLalpha domain located at the
      5' end of most var genes. We assessed the relationship between various DBLalpha
      tag classification methods, and sequence features that are only fully assessable
      through full-length var gene sequences. We compared these different sequence
      features in full-length var gene from six fully sequenced laboratory isolates.
      These comparisons show that despite a long history of recombination,  DBLalpha
      sequence tag classification can provide functional information on important
      features of full-length var genes. Notably, a specific subset of DBLalpha tags
      previously defined as "group A-like" is associated with CIDRalpha1 domains
      proposed to bind to endothelial protein C receptor. This analysis helps to bring
      together different sources of data that have been used to assess var gene
      expression in clinical parasite isolates.

PMID- 29062917
TI  - Single-cell heterogeneity and cell-cycle-related viral gene bursts in the human
      leukaemia virus HTLV-1.
AB  - Background: The human leukaemia virus HTLV-1 expresses essential accessory genes
      that manipulate the expression, splicing and transport of viral mRNAs.  Two of
      these genes, tax and hbz, also promote proliferation of the infected cell, and
      both genes are thought to contribute to oncogenesis in adult T-cell
      leukaemia/lymphoma.  The regulation of HTLV-1 proviral latency is not understood.
      tax, on the proviral plus strand, is usually silent in freshly-isolated cells,
      whereas the minus-strand-encoded hbz gene is persistently expressed at a low
      level.  However, the persistently activated host immune response to Tax indicates
      frequent expression of tax in vivo.  Methods: We used single-molecule RNA-FISH to
      quantify the expression of HTLV-1 transcripts at the single-cell level in a total
      of >19,000 cells from five T-cell clones, naturally infected with HTLV-1,
      isolated by limiting dilution from peripheral blood of HTLV-1-infected subjects. 
      Results: We found strong heterogeneity both within and between clones in the
      expression of the proviral plus-strand (detected by hybridization to the tax
      gene) and the minus-strand ( hbz gene). Both genes are transcribed in bursts; tax
      expression is enhanced in the absence of hbz, while hbz expression increased in
      cells with high tax expression. Surprisingly, we found that hbz expression is
      strongly associated with the S and G 2/M phases of the cell cycle, independent of
      tax expression.  Contrary to current belief, hbz is not expressed in all cells at
      all times, even within one clone.  In hbz-positive cells, the abundance of hbz
      transcripts showed a very strong positive linear correlation with nuclear volume.
      Conclusions: The occurrence of intense, intermittent plus-strand gene bursts in
      independent primary HTLV-1-infected T-cell clones from unrelated individuals
      strongly suggests that the HTLV-1 plus-strand is expressed in bursts in vivo. 
      Our results offer an explanation for the paradoxical correlations observed
      between the host immune response and HTLV-1 transcription.

PMID- 29062918
TI  - AMR Surveillance in low and middle-income settings - A roadmap for participation
      in the Global Antimicrobial Surveillance System (GLASS).
AB  - Drug-resistant infections caused by bacteria with increasing antimicrobial
      resistance (AMR) threaten our ability to treat life-threatening conditions.
      Tackling AMR requires international collaboration and partnership. An early and
      leading priority to do this is to strengthen AMR surveillance, particularly in
      low-income countries where the burden of infectious diseases is highest and where
      data are most limited. The World Health Organization (WHO) has developed the
      Global AMR Surveillance System (GLASS) as one of a number of measures designed to
      tackle the problem of AMR, and WHO member states have been encouraged to produce
      National Action Plans for AMR by 2017. However, low-income countries are unlikely
      to have the resources or capacity to implement all the components in the GLASS
      manual. To facilitate their efforts, we developed a guideline that is aligned to
      the GLASS procedures, but written specifically for implementation in low-income
      countries. The guideline allows for flexibility across different systems, but has
      sufficient standardisation of core protocols to ensure that, if followed, data
      will be valid and comparable. This will ensure that the surveillance programme
      can provide health intelligence data to inform evidence-based interventions at
      local, national and international levels.

PMID- 29062920
TI  - Uprising of synthetic and systems biotechnology.

PMID- 29062919
TI  - Drama as a community engagement strategy for malaria in rural Cambodia.
AB  - Background: Countries in Southeast Asia are working to eliminate multidrug
      resistant falciparum malaria, a major cause of mortality in tropical regions.
      Malaria is declining but transmission persists in many rural areas and among
      forest workers and isolated populations. In these remote communities,
      conventional health services and education are limited. Mobilising and educating
      these populations require new approaches as many people are illiterate and do not
      attend village meetings. This article describes a qualitative study to assess the
      feasibility of a drama project as a community engagement strategy. Methods: A
      drama project was conducted in twenty villages in Cambodia with three key
      messages: to use insecticide-treated bednets and repellents, to get early
      diagnosis and treatment, and to learn about risks of forest-acquired malaria.
      Qualitative interviews were conducted with the drama team members, village
      malaria workers, local health staffs and villagers, to explore the feasibility of
      using drama to engage the community and the associated challenges. Results: 29
      people were interviewed, which included 18 semi-structured interviews and one
      focus group discussion. Analysis of the interviews resulted in development of the
      following seven themes: i) exposure to malaria and engagement activities, ii)
      readiness and barriers to participation, iii) understanding and learning about
      malaria using drama, iv) entertainment value and engagement method preferences,
      v) challenges to community engagement, vi) future participation and vii)
      sustainability. The event saw a very positive response, with an encouraging
      average participation rate of 66%. The project faced several challenges including
      logistic problems, rescheduling due to raining season, and time- and budget
      constraints. Conclusions: Our evaluation demonstrated that the drama project was
      feasible in promoting awareness and understanding of malaria prevention and
      control. Audience members perceived drama as entertaining and as the preferred
      choice of engagement activity. Participatory drama could be considered as part of
      the community engagement for malaria elimination.

PMID- 29062921
TI  - Yeast knockout library allows for efficient testing of genomic mutations for cell
      free protein synthesis.
AB  - Cell-free protein synthesis (CFPS) systems from crude lysates have benefitted
      from modifications to their enzyme composition. For example, functionally
      deleting enzymes in the source strain that are deleterious to CFPS can improve
      protein synthesis yields. However, making such modifications can take substantial
      time. As a proof-of-concept to accelerate prototyping capabilities, we assessed
      the feasibility of using the yeast knockout collection to identify negative
      effectors in a Saccharomyces cerevisiae CFPS platform. We analyzed extracts made
      from six deletion strains that targeted the single deletion of potentially
      negative effectors (e.g., nucleases). We found a statistically significant
      increase in luciferase yields upon loss of function of GCN3, PEP4, PPT1, NGL3,
      and XRN1 with a maximum increase of over 6-fold as compared to the wild type. Our
      work has implications for yeast CFPS and for rapidly prototyping strains to
      enable cell-free synthetic biology applications.

PMID- 29062922
TI  - Interrogation of Streptomyces avermitilis for efficient production of
      avermectins.
AB  - The 2015 Nobel Prize in Physiology or Medicine has been awarded to avermectins
      and artemisinin, respectively. Avermectins produced by Streptomyces avermitilis
      are excellent anthelmintic and potential antibiotic agents. Because wild-type
      strains only produce low levels of avermectins, much research effort has focused
      on improvements in avermectin production to meet the ever increasing demand for
      such compounds. This review describes the strategies that have been widely
      employed and the future prospects of synthetic biology applications in avermectin
      yield improvement. With the help of genome sequencing of S. avermitilis and an
      understanding of the avermectin biosynthetic/regulatory pathways, synthetic and
      systems biotechnology approaches have been applied for precision engineering. We
      focus on the design and synthesis of biological chassis, parts, devices, and
      modules from diverse microbes to reconstruct and optimize their dynamic
      processes, as well as predict favorable effective overproduction of avermectins
      by a 4Ms strategy (Mine, Model, Manipulation, and Measurement).

PMID- 29062923
TI  - Mechanisms of biotin-regulated gene expression in microbes.
AB  - Biotin is an essential micronutrient that acts as a co-factor for biotin
      dependent metabolic enzymes. In bacteria, the supply of biotin can be achieved by
      de novo synthesis or import from exogenous sources. Certain bacteria are able to
      obtain biotin through both mechanisms while others can only fulfill their biotin
      requirement through de novo synthesis. Inability to fulfill their cellular demand
      for biotin can have detrimental consequences on cell viability and virulence.
      Therefore understanding the transcriptional mechanisms that regulate biotin
      biosynthesis and transport will extend our knowledge about bacterial survival and
      metabolic adaptation during pathogenesis when the supply of biotin is limited.
      The most extensively characterized protein that regulates biotin synthesis and
      uptake is BirA. In certain bacteria, such as Escherichia coli and Staphylococcus
      aureus, BirA is a bi-functional protein that serves as a transcriptional
      repressor to regulate biotin biosynthesis genes, as well as acting as a ligase to
      catalyze the biotinylation of biotin-dependent enzymes. Recent studies have
      identified two other proteins that also regulate biotin synthesis and transport,
      namely BioQ and BioR. This review summarizes the different transcriptional
      repressors and their mechanism of action. Moreover, the ability to regulate the
      expression of target genes through the activity of a vitamin, such as biotin, may
      have biotechnological applications in synthetic biology.

PMID- 29062925
TI  - Improved production of cytotoxic thailanstatins A and D through metabolic
      engineering of Burkholderia thailandensis MSMB43 and pilot scale fermentation.
AB  - Thailanstatin A (TST-A) is a potent antiproliferative natural product discovered
      by our group from Burkholderia thailandensis MSMB43 through a genome-guided
      approach. The limited supply of TST-A, due to its low titer in bacterial
      fermentation, modest stability and very low recovery rate during purification,
      has hindered the investigations of TST-A as an anticancer drug candidate. Here we
      report the significant yield improvement of TST-A and its direct precursor,
      thailanstatin D (TST-D), through metabolic engineering of the thailanstatin
      biosynthetic pathway in MSMB43. Deletion of tstP, which encodes a dioxygenase
      involved in converting TST-A to downstream products including FR901464 (FR),
      resulted in 58% increase of the TST-A titer to 144.7 +/- 2.3 mg/L and 132%
      increase of the TST-D titer to 14.6 +/- 0.5 mg/L in the fermentation broth,
      respectively. Deletion of tstR, which encodes a cytochrome P450 involved in
      converting TST-D to TST-A, resulted in more than 7-fold increase of the TST-D
      titer to 53.2 +/- 12.1 mg/L in the fermentation broth. An execution of 90 L pilot
      scale fed-batch fermentation of the tstP deletion mutant in a 120-L fermentor led
      to the preparation of 714 mg of TST-A with greater than 98.5% purity. The half
      life of TST-D in a phosphate buffer was found to be at least 202 h, significantly
      longer than that of TST-A or FR, suggesting superior stability. However, the IC50
      values of TST-D against representative human cancer cell lines were determined to
      be greater than those of TST-A, indicating weaker antiproliferative activity.
      This work enabled us to prepare sufficient quantities of TST-A and TST-D for our
      ongoing translational research.

PMID- 29062924
TI  - In vitro reconstitution guide for targeted synthetic metabolism of chemicals,
      nutraceuticals and drug precursors.
AB  - With the developments in metabolic engineering and the emergence of synthetic
      biology, many breakthroughs in medicinal, biological and chemical products as
      well as biofuels have been achieved in recent decades. As an important barrier to
      traditional metabolic engineering, however, the identification of rate-limiting
      step(s) for the improvement of specific cellular functions is often difficult.
      Meanwhile, in the case of synthetic biology, more and more BioBricks could be
      constructed for targeted purposes, but the optimized assembly or engineering of
      these components for high-efficiency cell factories is still a challenge. Owing
      to the lack of steady-state kinetic data for overall flux, balancing many
      multistep biosynthetic pathways is time-consuming and needs vast resources of
      labor and materials. A strategy called targeted engineering is proposed in an
      effort to solve this problem. Briefly, a targeted biosynthetic pathway is to be
      reconstituted in vitro and then the contribution of cofactors, substrates and
      each enzyme will be analyzed systematically. Next is in vivo engineering or de
      novo pathway assembly with the guidance of information gained from in vitro
      assays. To demonstrate its practical application, biosynthesis pathways for the
      production of important products, e.g. chemicals, nutraceuticals and drug
      precursors, have been engineered in Escherichia coli and Saccharomyces
      cerevisiae. These cases can be regarded as concept proofs indicating targeted
      engineering might help to create high-efficiency cell factories based upon
      constructed biological components.

PMID- 29062926
TI  - Inactivation of SACE_3446, a TetR family transcriptional regulator, stimulates
      erythromycin production in Saccharopolyspora erythraea.
AB  - Erythromycin A is a widely used antibiotic produced by Saccharopolyspora
      erythraea; however, its biosynthetic cluster lacks a regulatory gene, limiting
      the yield enhancement via regulation engineering of S. erythraea. Herein, six
      TetR family transcriptional regulators (TFRs) belonging to three genomic context
      types were individually inactivated in S. erythraea A226, and one of them,
      SACE_3446, was proved to play a negative role in regulating erythromycin
      biosynthesis. EMSA and qRT-PCR analysis revealed that SACE_3446 covering intact N
      terminal DNA binding domain specifically bound to the promoter regions of
      erythromycin biosynthetic gene eryAI, the resistant gene ermE and the adjacent
      gene SACE_3447 (encoding a long-chain fatty-acid CoA ligase), and repressed their
      transcription. Furthermore, we explored the interaction relationships of
      SACE_3446 and previously identified TFRs (SACE_3986 and SACE_7301) associated
      with erythromycin production. Given demonstrated relatively independent
      regulation mode of SACE_3446 and SACE_3986 in erythromycin biosynthesis, we
      individually and concomitantly inactivated them in an industrial S. erythraea WB.
      Compared with WB, the WBDelta3446 and WBDelta3446Delta3986 mutants respectively
      displayed 36% and 65% yield enhancement of erythromycin A, following
      significantly elevated transcription of eryAI and ermE. When cultured in a 5 L
      fermentor, erythromycin A of WBDelta3446 and WBDelta3446Delta3986 successively
      reached 4095 mg/L and 4670 mg/L with 23% and 41% production improvement relative
      to WB. The strategy reported here will be useful to improve antibiotics
      production in other industrial actinomycete.

PMID- 29062927
TI  - Systematic development of biomass overproducing Scheffersomyces stipitis for high
      cell-density fermentations.
AB  - The development of economically feasible bio-based process requires efficient
      cell factories capable of producing the desired product at high titer under high
      cell-density fermentation. Herein we present a combinatorial approach based on
      systems metabolic engineering and metabolic evolution for the development of
      efficient biomass-producing strain. Systems metabolic engineering guided by flux
      balance analysis (FBA) was first employed to rationally design mutant strains of
      Scheffersomyces stipitis with high biomass yield. By experimentally implementing
      these mutations, the biomass yield was improved by 30% in GPD1, 25% in TKL1, 30%
      in CIT1, and 44% in ZWF1 overexpressed mutants compared to wild-type. These
      designed mutants were further fine-tuned through metabolic evolution resulting in
      the maximal biomass yield of 0.49 g-cdw/g-glucose, which matches well with
      predicted yield phenotype. The constructed mutants are beneficial for
      biotechnology applications dealing with high cell titer cultivations. This work
      demonstrates a solid confirmation of systems metabolic engineering in combination
      with metabolic evolution approach for efficient strain development, which could
      assist in rapid optimization of cell factory for an economically viable and
      sustainable bio-based process.

PMID- 29062929
TI  - Introduction to the Special Issue "Bioinformatic tools and approaches for
      Synthetic Biology of natural products".

PMID- 29062928
TI  - Genome mining reveals the biosynthetic potential of the marine-derived strain
      Streptomyces marokkonensis M10.
AB  - Marine streptomycetes are rich sources of natural products with novel structures
      and interesting biological activities, and genome mining of marine streptomycetes
      facilitates rapid discovery of their useful products. In this study, a marine
      derived Streptomyces sp. M10 was revealed to share a 99.02% 16S rDNA sequence
      identity with that of Streptomyces marokkonensis Ap1T, and was thus named S.
      marokkonensis M10. To further evaluate its biosynthetic potential, the 7,207,169
      bps of S. marokkonensis M10 genome was sequenced. Genomic sequence analysis for
      potential secondary metabolite-associated gene clusters led to the identification
      of at least three polyketide synthases (PKSs), six non-ribosomal peptide
      synthases (NRPSs), one hybrid NRPS-PKS, two lantibiotic and five terpene
      biosynthetic gene clusters. One type I PKS gene cluster was revealed to share
      high nucleotide similarity with the candicidin/FR008 gene cluster, indicating the
      capacity of this microorganism to produce polyene macrolides. This assumption was
      further verified by isolation of two polyene family compounds PF1 and PF2, which
      have the characteristic UV adsorption at 269, 278, 290 nm (PF1) and 363, 386 and
      408 nm (PF2), respectively. S. marokkonensis M10 is therefore a new source of
      polyene metabolites. Further studies on S. marokkonensis M10 will provide more
      insights into natural product biosynthesis potential of related streptomycetes.
      This is also the first report to describe the genome sequence of S. marokkonensis
      related strain.

PMID- 29062930
TI  - The secondary metabolite bioinformatics portal: Computational tools to facilitate
      synthetic biology of secondary metabolite production.
AB  - Natural products are among the most important sources of lead molecules for drug
      discovery. With the development of affordable whole-genome sequencing
      technologies and other 'omics tools, the field of natural products research is
      currently undergoing a shift in paradigms. While, for decades, mainly analytical
      and chemical methods gave access to this group of compounds, nowadays genomics
      based methods offer complementary approaches to find, identify and characterize
      such molecules. This paradigm shift also resulted in a high demand for
      computational tools to assist researchers in their daily work. In this context,
      this review gives a summary of tools and databases that currently are available
      to mine, identify and characterize natural product biosynthesis pathways and
      their producers based on 'omics data. A web portal called Secondary Metabolite
      Bioinformatics Portal (SMBP at http://www.secondarymetabolites.org) is introduced
      to provide a one-stop catalog and links to these bioinformatics resources. In
      addition, an outlook is presented how the existing tools and those to be
      developed will influence synthetic biology approaches in the natural products
      field.

PMID- 29062931
TI  - In silico methods for linking genes and secondary metabolites: The way forward.
AB  - In silico methods for linking genomic space to chemical space have played a
      crucial role in genomics driven discovery of new natural products as well as
      biosynthesis of altered natural products by engineering of biosynthetic pathways.
      Here we give an overview of available computational tools and then briefly
      describe a novel computational framework, namely retro-biosynthetic enumeration
      of biosynthetic reactions, which can add to the repertoire of computational tools
      available for connecting natural products to their biosynthetic gene clusters.
      Most of the currently available bioinformatics tools for analysis of secondary
      metabolite biosynthetic gene clusters utilize the "Genes to Metabolites"
      approach. In contrast to the "Genes to Metabolites" approach, the "Metabolites to
      Genes" or retro-biosynthetic approach would involve enumerating the various
      biochemical transformations or enzymatic reactions which would generate the given
      chemical moiety starting from a set of precursor molecules and identifying
      enzymatic domains which can potentially catalyze the enumerated biochemical
      transformations. In this article, we first give a brief overview of the presently
      available in silico tools and approaches for analysis of secondary metabolite
      biosynthetic pathways. We also discuss our preliminary work on development of
      algorithms for retro-biosynthetic enumeration of biochemical transformations to
      formulate a novel computational method for identifying genes associated with
      biosynthesis of a given polyketide or nonribosomal peptide.

PMID- 29062934
TI  - CRISPy-web: An online resource to design sgRNAs for CRISPR applications.
AB  - CRISPR/Cas9-based genome editing has been one of the major achievements of
      molecular biology, allowing the targeted engineering of a wide range of genomes.
      The system originally evolved in prokaryotes as an adaptive immune system against
      bacteriophage infections. It now sees widespread application in genome
      engineering workflows, especially using the Streptococcus pyogenes endonuclease
      Cas9. To utilize Cas9, so-called single guide RNAs (sgRNAs) need to be designed
      for each target gene. While there are many tools available to design sgRNAs for
      the popular model organisms, only few tools that allow designing sgRNAs for non
      model organisms exist. Here, we present CRISPy-web
      (http://crispy.secondarymetabolites.org/), an easy to use web tool based on
      CRISPy to design sgRNAs for any user-provided microbial genome. CRISPy-web allows
      researchers to interactively select a region of their genome of interest to scan
      for possible sgRNAs. After checks for potential off-target matches, the resulting
      sgRNA sequences are displayed graphically and can be exported to text files. All
      steps and information are accessible from a web browser without the requirement
      to install and use command line scripts.

PMID- 29062935
TI  - FunGeneClusterS: Predicting fungal gene clusters from genome and transcriptome
      data.
AB  - INTRODUCTION: Secondary metabolites of fungi are receiving an increasing amount
      of interest due to their prolific bioactivities and the fact that fungal
      biosynthesis of secondary metabolites often occurs from co-regulated and co
      located gene clusters. This makes the gene clusters attractive for synthetic
      biology and industrial biotechnology applications. We have previously published a
      method for accurate prediction of clusters from genome and transcriptome data,
      which could also suggest cross-chemistry, however, this method was limited both
      in the number of parameters which could be adjusted as well as in user
      friendliness. Furthermore, sensitivity to the transcriptome data required manual
      curation of the predictions. In the present work, we have aimed at improving
      these features. RESULTS: FunGeneClusterS is an improved implementation of our
      previous method with a graphical user interface for off- and on-line use. The new
      method adds options to adjust the size of the gene cluster(s) being sought as
      well as an option for the algorithm to be flexible with genes in the cluster
      which may not seem to be co-regulated with the remainder of the cluster. We have
      benchmarked the method using data from the well-studied Aspergillus nidulans and
      found that the method is an improvement over the previous one. In particular, it
      makes it possible to predict clusters with more than 10 genes more accurately,
      and allows identification of co-regulated gene clusters irrespective of the
      function of the genes. It also greatly reduces the need for manual curation of
      the prediction results. We furthermore applied the method to transcriptome data
      from A. niger. Using the identified best set of parameters, we were able to
      identify clusters for 31 out of 76 previously predicted secondary metabolite
      synthases/synthetases. Furthermore, we identified additional putative secondary
      metabolite gene clusters. In total, we predicted 432 co-transcribed gene clusters
      in A. niger (spanning 1.323 genes, 12% of the genome). Some of these had
      functions related to primary metabolism, e.g. we have identified a cluster for
      biosynthesis of biotin, as well as several for degradation of aromatic compounds.
      The data identifies that suggests that larger parts of the fungal genome than
      previously anticipated operates as gene clusters. This includes both primary and
      secondary metabolism as well as other cellular maintenance functions. CONCLUSION:
      We have developed FunGeneClusterS in a graphical implementation and made the
      method capable of adjustments to different datasets and target clusters. The
      method is versatile in that it can predict co-regulated clusters not limited to
      secondary metabolism. Our analysis of data has shown not only the validity of the
      method, but also strongly suggests that large parts of fungal primary metabolism
      and cellular functions are both co-regulated and co-located.

PMID- 29062933
TI  - Design, analysis and application of synthetic microbial consortia.
AB  - The rapid development of synthetic biology has conferred almost perfect
      modification on single cells, and provided methodological support for
      synthesizing microbial consortia, which have a much wider application potential
      than synthetic single cells. Co-cultivating multiple cell populations with
      rational strategies based on interacting relationships within natural microbial
      consortia provides theoretical as well as experimental support for the successful
      obtaining of synthetic microbial consortia, promoting it into extensive research
      on both industrial applications in plenty of areas and also better understanding
      of natural microbial consortia. According to their composition complexity,
      synthetic microbial consortia are summarized in three aspects in this review and
      are discussed in principles of design and construction, insights and methods for
      analysis, and applications in energy, healthcare, etc.

PMID- 29062932
TI  - Generate a bioactive natural product library by mining bacterial cytochrome P450
      patterns.
AB  - The increased number of annotated bacterial genomes provides a vast resource for
      genome mining. Several bacterial natural products with epoxide groups have been
      identified as pre-mRNA spliceosome inhibitors and antitumor compounds through
      genome mining. These epoxide-containing natural products feature a common
      biosynthetic characteristic that cytochrome P450s (CYPs) and its patterns such as
      epoxidases are employed in the tailoring reactions. The tailoring enzyme patterns
      are essential to both biological activities and structural diversity of natural
      products, and can be used for enzyme pattern-based genome mining. Recent
      development of direct cloning, heterologous expression, manipulation of the
      biosynthetic pathways and the CRISPR-CAS9 system have provided molecular biology
      tools to turn on or pull out nascent biosynthetic gene clusters to generate a
      microbial natural product library. This review focuses on a library of epoxide
      containing natural products and their associated CYPs, with the intention to
      provide strategies on diversifying the structures of CYP-catalyzed bioactive
      natural products. It is conceivable that a library of diversified bioactive
      natural products will be created by pattern-based genome mining, direct cloning
      and heterologous expression as well as the genomic manipulation.

PMID- 29062936
TI  - Informatic analysis reveals Legionella as a source of novel natural products.
AB  - Microbial natural products are a crucial source of bioactive molecules and unique
      chemical scaffolds. Despite their importance, rediscovery of known natural
      products from established productive microbes has led to declining interest, even
      while emergent genomic data suggest that the majority of microbial natural
      products remain to be discovered. Now, new sources of microbial natural products
      must be defined in order to provide chemical scaffolds for the next generation of
      small molecules for therapeutic, agricultural, and industrial purposes. In this
      work, we use specialized bioinformatic programs, genetic knockouts, and
      comparative metabolomics to define the genus Legionella as a new source of novel
      natural products. We show that Legionella spp. hold a diverse collection of
      biosynthetic gene clusters for the production of polyketide and nonribosomal
      peptide natural products. To confirm this bioinformatic survey, we create
      targeted mutants of L. pneumophila and use comparative metabolomics to identify a
      novel polyketide surfactant. Using spectroscopic techniques, we show that this
      polyketide possesses a new chemical scaffold, and firmly demonstrate that this
      unexplored genus is a source for novel natural products.

PMID- 29062937
TI  - The application of microfluidic-based technologies in the cycle of metabolic
      engineering.
AB  - The process of metabolic engineering consists of multiple cycles of design,
      build, test and learn, which is typically laborious and time-consuming. To
      increase the efficiency and the rate of success of strain engineering, novel
      instrumentation must be applied. Microfluidics, the control of liquid flow in
      microstructures, has enabled flexible, accurate, automatic, and high-throughput
      manipulation of cells in liquid at picoliter to nanoliter scale. These attributes
      hold great promise in advancing metabolic engineering in terms of the phases of
      design, build, test and learn. To promote the application of microfluidic-based
      technologies in strain improvement, this review addressed the potentials of
      microfluidics and the related approaches in DNA assembly, transformation, strain
      screening, genotyping and phenotyping, and highlighted their adaptations for
      single-cell analysis. As a result, this facilitates in-depth understanding of the
      metabolic network, which in turn promote efficient optimization in the following
      cycles of strain engineering. Taken together, microfluidic-based technologies
      enable on-chip workflow, and could greatly accelerate the turnaround of metabolic
      engineering.

PMID- 29062938
TI  - Study on genetic engineering of Acremonium chrysogenum, the cephalosporin C
      producer.
AB  - Acremonium chrysogenum is an important filamentous fungus which produces
      cephalosporin C in industry. This review summarized the study on genetic
      engineering of Acremonium chrysogenum, including biosynthesis and regulation for
      fermentation of cephalosporin C, molecular techniques, molecular breeding and
      transcriptomics of Acremonium chrysogenum. We believe with all the techniques
      available and full genomic sequence, the industrial strain of Acremonium
      chrysogenum can be genetically modified to better serve the pharmaceutical
      industry.

PMID- 29062939
TI  - Absolute quantification of proteins in the fatty acid biosynthetic pathway using
      protein standard absolute quantification.
AB  - With worldwide attention on renewable energy and climate change, metabolic
      engineering of the fatty acid biosynthetic pathway has become an active area of
      research, with a view to enhance production of biofuels. Indeed, this pathway has
      already been extensively studied in Escherichia coli. Nevertheless, little is
      known about the absolute abundance of the enzymes involved, information that may
      be valuable for engineering, such as the optimal molar ratios of different
      proteins. In this study, we use protein standard absolute quantification (PSAQ)
      to measure the absolute abundance of proteins that catalyze fatty acid
      biosynthesis in E. coli. In addition, the changes of protein abundance were
      analyzed by comparing the differences between high-yield and the background
      strain. Our work highlights opportunities to enhance fatty acid production by
      measuring protein molar ratios and identifying catalytic and regulatory
      bottlenecks. More importantly, our results provide evidence that PSAQ is a
      generally valuable tool to investigate metabolic pathways.

PMID- 29062940
TI  - Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC
      transporters.
AB  - Multi-drug resistance of pathogenic microorganisms is becoming a serious threat,
      particularly to immunocompromised populations. The high mortality of systematic
      fungal infections necessitates novel antifungal drugs and therapies.
      Unfortunately, with traditional drug discovery approaches, only echinocandins was
      approved by FDA as a new class of antifungals in the past two decades. Drug
      efflux is one of the major contributors to multi-drug resistance, the modulator
      of drug efflux pumps is considered as one of the keys to conquer multi-drug
      resistance. In this study, we combined structure-based virtual screening and
      whole-cell based mechanism study, identified a natural product, beauvericin (BEA)
      as a drug efflux pump modulator, which can reverse the multi-drug resistant
      phenotype of Candida albicans by specifically blocking the ATP-binding cassette
      (ABC) transporters; meantime, BEA alone has fungicidal activity in vitro by
      elevating intracellular calcium and reactive oxygen species (ROS). It was further
      demonstrated by histopathological study that BEA synergizes with a sub
      therapeutic dose of ketoconazole (KTC) and could cure the murine model of
      disseminated candidiasis. Toxicity evaluation of BEA, including acute toxicity
      test, Ames test, and hERG (human ether-a-go-go-related gene) test promised that
      BEA can be harnessed for treatment of candidiasis, especially the candidiasis
      caused by ABC overexpressed multi-drug resistant C. albicans.

PMID- 29062942
TI  - Discovery of tanshinone derivatives with anti-MRSA activity via targeted bio
      transformation.
AB  - Two potent anti-MRSA tanshinone glycosides (1 and 2) were discovered by targeted
      microbial biotransformation, along with rapid identification via MS/MS
      networking. Serial reactions including dehydrogenation, demethylations,
      reduction, glycosylation and methylation have been observed after incubation of
      tanshinone IIA and fungus Mucor rouxianus AS 3.3447. In addition, tanshinosides B
      (2) showed potent activities against serial clinical isolates of oxacillin
      resistant Staphylococcus aureus with MIC values of 0.78 MUg/mL. This is the first
      study that shows a significant increase in the level and activities of tanshinone
      glycosides relative to the substrate tanshinone IIA.

PMID- 29062941
TI  - A systematic study of the whole genome sequence of Amycolatopsis methanolica
      strain 239T provides an insight into its physiological and taxonomic properties
      which correlate with its position in the genus.
AB  - The complete genome of methanol-utilizing Amycolatopsis methanolica strain 239T
      was generated, revealing a single 7,237,391 nucleotide circular chromosome with
      7074 annotated protein-coding sequences (CDSs). Comparative analyses against the
      complete genome sequences of Amycolatopsis japonica strain MG417-CF17T,
      Amycolatopsis mediterranei strain U32 and Amycolatopsis orientalis strain
      HCCB10007 revealed a broad spectrum of genomic structures, including various
      genome sizes, core/quasi-core/non-core configurations and different kinds of
      episomes. Although polyketide synthase gene clusters were absent from the A.
      methanolica genome, 12 gene clusters related to the biosynthesis of other
      specialized (secondary) metabolites were identified. Complete pathways
      attributable to the facultative methylotrophic physiology of A. methanolica
      strain 239T, including both the mdo/mscR encoded methanol oxidation and the
      hps/hpi encoded formaldehyde assimilation via the ribulose monophosphate cycle,
      were identified together with evidence that the latter might be the result of
      horizontal gene transfer. Phylogenetic analyses based on 16S rDNA or orthologues
      of AMETH_3452, a novel actinobacterial class-specific conserved gene against 62
      or 18 Amycolatopsis type strains, respectively, revealed three major phyletic
      lineages, namely the mesophilic or moderately thermophilic A. orientalis subclade
      (AOS), the mesophilic Amycolatopsis taiwanensis subclade (ATS) and the
      thermophilic A. methanolica subclade (AMS). The distinct growth temperatures of
      members of the subclades correlated with corresponding genetic variations in
      their encoded compatible solutes. This study shows the value of integrating
      conventional taxonomic with whole genome sequence data.

PMID- 29062945
TI  - Synthetic biology in China, UK and US.

PMID- 29062943
TI  - Sequence homolog-based molecular engineering for shifting the enzymatic pH
      optimum.
AB  - Cell-free synthetic biology system organizes multiple enzymes (parts) from
      different sources to implement unnatural catalytic functions. Highly adaption
      between the catalytic parts is crucial for building up efficient artificial
      biosynthetic systems. Protein engineering is a powerful technology to tailor
      various enzymatic properties including catalytic efficiency, substrate
      specificity, temperature adaptation and even achieve new catalytic functions.
      However, altering enzymatic pH optimum still remains a challenging task. In this
      study, we proposed a novel sequence homolog-based protein engineering strategy
      for shifting the enzymatic pH optimum based on statistical analyses of sequence
      function relationship data of enzyme family. By two statistical procedures,
      artificial neural networks (ANNs) and least absolute shrinkage and selection
      operator (Lasso), five amino acids in GH11 xylanase family were identified to be
      related to the evolution of enzymatic pH optimum. Site-directed mutagenesis of a
      thermophilic xylanase from Caldicellulosiruptor bescii revealed that four out of
      five mutations could alter the enzymatic pH optima toward acidic condition
      without compromising the catalytic activity and thermostability. Combination of
      the positive mutants resulted in the best mutant M31 that decreased its pH
      optimum for 1.5 units and showed increased catalytic activity at pH < 5.0
      compared to the wild-type enzyme. Structure analysis revealed that all the
      mutations are distant from the active center, which may be difficult to be
      identified by conventional rational design strategy. Interestingly, the four
      mutation sites are clustered at a certain region of the enzyme, suggesting a
      potential "hot zone" for regulating the pH optima of xylanases. This study
      provides an efficient method of modulating enzymatic pH optima based on
      statistical sequence analyses, which can facilitate the design and optimization
      of suitable catalytic parts for the construction of complicated cell-free
      synthetic biology systems.

PMID- 29062944
TI  - Development of Streptomyces sp. FR-008 as an emerging chassis.
AB  - Microbial-derived natural products are important in both the pharmaceutical
      industry and academic research. As the metabolic potential of original producer
      especially Streptomyces is often limited by slow growth rate, complicated
      cultivation profile, and unfeasible genetic manipulation, so exploring a
      Streptomyces as a super industrial chassis is valuable and urgent. Streptomyces
      sp. FR-008 is a fast-growing microorganism and can also produce a considerable
      amount of macrolide candicidin via modular polyketide synthase. In this study, we
      evaluated Streptomyces sp. FR-008 as a potential industrial-production chassis.
      First, PacBio sequencing and transcriptome analyses indicated that the
      Streptomyces sp. FR-008 genome size is 7.26 Mb, which represents one of the
      smallest of currently sequenced Streptomyces genomes. In addition, we simplified
      the conjugation procedure without heat-shock and pre-germination treatments but
      with high conjugation efficiency, suggesting it is inherently capable of
      accepting heterologous DNA. In addition, a series of promoters selected from
      literatures was assessed based on GusA activity in Streptomyces sp. FR-008.
      Compared with the common used promoter ermE*-p, the strength of these promoters
      comprise a library with a constitutive range of 60-860%, thus providing the
      useful regulatory elements for future genetic engineering purpose. In order to
      minimum the genome, we also target deleted three endogenous polyketide synthase
      (PKS) gene clusters to generate a mutant LQ3. LQ3 is thus an "updated" version of
      Streptomyces sp. FR-008, producing fewer secondary metabolites profiles than
      Streptomyces sp. FR-008. We believe this work could facilitate further
      development of Streptomyces sp. FR-008 for use in biotechnological applications.

PMID- 29062946
TI  - Recent development on synthetic biological devices treating bladder cancer.
AB  - Synthetic biology is an emerging field focusing on engineering genetic devices
      and biomolecular systems for a variety of applications from basic biology to
      biotechnology and medicine. Thanks to the tremendous advances in genomics and the
      chemical synthesis of DNA in the past decade, scientists are now able to engineer
      genetic devices and circuits for cancer research and intervention, which offer
      promising therapeutic strategies for cancer treatment. In this article, we
      provide a systemic review on recent development achieved by the synthetic
      biologists, oncologists and clinicians of one National "973" Plan. We expand the
      synthetic biology toolkits involving DNA, RNA and protein bio-parts to explore
      various issues in cancer research, such as elucidation of mechanisms and
      pathways, creation of new diagnostic tools and invention of novel therapeutic
      approaches. We claimed that the Chinese synthetic biologists are promoting the
      basic research productions of tumor synthetic biology into the clinic.

PMID- 29062947
TI  - Synbiological systems for complex natural products biosynthesis.
AB  - Natural products (NPs) continue to play a pivotal role in drug discovery
      programs. The rapid development of synthetic biology has conferred the strategies
      of NPs production. Synthetic biology is a new engineering discipline that aims to
      produce desirable products by rationally programming the biological parts and
      manipulating the pathways. However, there is still a challenge for integrating a
      heterologous pathway in chassis cells for overproduction purpose due to the
      limited characterized parts, modules incompatibility, and cell tolerance towards
      product. Enormous endeavors have been taken for mentioned issues. Herein, in this
      review, the progresses in naturally discovering novel biological parts and
      rational design of synthetic biological parts are reviewed, combining with the
      advanced assembly technologies, pathway engineering, and pathway optimization in
      global network guidance. The future perspectives are also presented.

PMID- 29062948
TI  - Design and construction of synthetic microbial consortia in China.
AB  - The rapid development of synthetic biology enables the design, construction and
      optimization of synthetic microbial consortia to achieve specific functions. In
      China, the "973" project-"Design and Construction of Microbial Consortia" was
      funded by the National Basic Research Program of China in January 2014. It was
      proposed to address the fundamental challenges in engineering natural microbial
      consortia and reconstructing microbial consortia to meet industrial demands. In
      this review, we will introduce this "973" project, including the significance of
      microbial consortia, the fundamental scientific issues, the recent research
      progresses, and some case studies about synthetic microbial consortia in the past
      two and a half years.

PMID- 29062950
TI  - Synthetic biology in the UK - An outline of plans and progress.
AB  - Synthetic biology is capable of delivering new solutions to key challenges
      spanning the bioeconomy, both nationally and internationally. Recognising this
      significant potential and the associated need to facilitate its translation and
      commercialisation the UK government commissioned the production of a national
      Synthetic Biology Roadmap in 2011, and subsequently provided crucial support to
      assist its implementation. Critical infrastructural investments have been made,
      and important strides made towards the development of an effectively connected
      community of practitioners and interest groups. A number of Synthetic Biology
      Research Centres, DNA Synthesis Foundries, a Centre for Doctoral Training, and an
      Innovation Knowledge Centre have been established, creating a nationally
      distributed and integrated network of complementary facilities and expertise. The
      UK Synthetic Biology Leadership Council published a UK Synthetic Biology
      Strategic Plan in 2016, increasing focus on the processes of translation and
      commercialisation. Over 50 start-ups, SMEs and larger companies are actively
      engaged in synthetic biology in the UK, and inward investments are starting to
      flow. Together these initiatives provide an important foundation for stimulating
      innovation, actively contributing to international research and development
      partnerships, and helping deliver useful benefits from synthetic biology in
      response to local and global needs and challenges.

PMID- 29062949
TI  - Synthetic biology of microbes synthesizing polyhydroxyalkanoates (PHA).
AB  - Microbial polyhydroxyalkanoates (PHA) have been produced as bioplastics for
      various purposes. Under the support of China National Basic Research 973 Project,
      we developed synthetic biology methods to diversify the PHA structures into homo
      , random, block polymers with improved properties to better meet various
      application requirements. At the same time, various pathways were assembled to
      produce various PHA from glucose as a simple carbon source. At the end, Halomonas
      bacteria were reconstructed to produce PHA in changing morphology for low cost
      production under unsterile and continuous conditions. The synthetic biology will
      advance the PHA into a bio- and material industry.

PMID- 29062951
TI  - A brief overview of synthetic biology research programs and roadmap studies in
      the United States.
AB  - The United States is a leading nation in the development of synthetic biology, an
      emerging engineering discipline to create, control and reprogram biological
      systems. With strategic investment from its government agencies, the U.S. has
      established numerous research centers and programs in synthetic biology, enabling
      significant advances in foundational tool development and practical applications
      ranging from bioenergy, biomanufacturing, to biomedicine. To maintain its
      leadership in synthetic biology, U.S, has conducted several roadmap studies to
      provide strategic visions and action recommendations. Here we will provide a
      brief overview of the major research programs and roadmap studies of synthetic
      biology in the U.S.

PMID- 29062954
TI  - Introduction to the Special Issue: "Arnold Demain - Industrial microbiologist
      extraodinaire".

PMID- 29062952
TI  - Visualized and precise design of artificial small RNAs for regulating T7 RNA
      polymerase and enhancing recombinant protein folding in Escherichia coli.
AB  - Small non-coding RNAs (sRNAs) have received much attention in recent years due to
      their unique biological properties, which can efficiently and specifically tune
      target gene expressions in bacteria. Inspired by natural sRNAs, recent works have
      proposed the use of artificial sRNAs (asRNAs) as genetic tools to regulate
      desired gene that has been applied in several fields, such as metabolic
      engineering and bacterial physiology studies. However, the rational design of
      asRNAs is still a challenge. In this study, we proposed structure and length as
      two criteria to implement rational visualized and precise design of asRNAs. T7
      expression system was one of the most useful recombinant protein expression
      systems. However, it was deeply limited by the formation of inclusion body. To
      settle this problem, we designed a series of asRNAs to inhibit the T7 RNA
      polymerase (Gene1) expression to balance the rate between transcription and
      folding of recombinant protein. Based on the heterologous expression of
      Aspergillus oryzae Li-3 glucuronidase in E. coli, the asRNA-antigene1-17bp can
      effectively decrease the inclusion body and increase the enzyme activity by
      169.9%.

PMID- 29062955
TI  - Conditional knockout tools: Application of site-specific incorporation of
      unnatural amino acid via genetic code expansion in viral and parasite vaccine
      development.

PMID- 29062953
TI  - SYNBIOCHEM Synthetic Biology Research Centre, Manchester - A UK foundry for fine
      and speciality chemicals production.
AB  - The UK Synthetic Biology Research Centre, SYNBIOCHEM, hosted by the Manchester
      Institute of Biotechnology at the University of Manchester is delivering
      innovative technology platforms to facilitate the predictable engineering of
      microbial bio-factories for fine and speciality chemicals production. We provide
      an overview of our foundry activities that are being applied to grand challenge
      projects to deliver innovation in bio-based chemicals production for industrial
      biotechnology.

PMID- 29062957
TI  - Reactive oxygen species and antioxidant properties from mushrooms.
AB  - Preventive medicine and food industry have shown an increased interest in the
      development of natural antioxidants, since those most commonly used synthetic
      antioxidants may have restricted use in food. This could explain why there is
      currently much research on the antioxidant properties from natural products such
      as mushrooms. Many mushrooms have been reported to possess antioxidant
      properties, which enable them to neutralize free radicals. The oxygen molecule is
      a free radical, which lead to the generation of the reactive oxygen species and
      can damage the cells. Cell damage caused by free radicals appears to be a major
      contributor to aging and degenerative diseases. Mushrooms antioxidant components
      are found in fruit bodies, mycelium and culture both, which include
      polysaccharides, tocopherols, phenolics, carotenoids, ergosterol and ascorbic
      acid among others. Fruit bodies or mycelium can be manipulated to produce active
      compounds in a relatively short period of time, which represent a significant
      advantage in antioxidant compounds extraction from mushrooms. Antioxidant
      compounds may be extracted to be used as functional additives or mushrooms can be
      incorporated into our food regime, representing an alternative source of food to
      prevent damage caused by oxidation in the human body.

PMID- 29062958
TI  - Cell-free synthetic biology: Engineering in an open world.
AB  - Cell-free synthetic biology emerges as a powerful and flexible enabling
      technology that can engineer biological parts and systems for life science
      applications without using living cells. It provides simpler and faster
      engineering solutions with an unprecedented freedom of design in an open
      environment than cell system. This review focuses on recent developments of cell
      free synthetic biology on biological engineering fields at molecular and cellular
      levels, including protein engineering, metabolic engineering, and artificial cell
      engineering. In cell-free protein engineering, the direct control of reaction
      conditions in cell-free system allows for easy synthesis of complex proteins,
      toxic proteins, membrane proteins, and novel proteins with unnatural amino acids.
      Cell-free systems offer the ability to design metabolic pathways towards the
      production of desired products. Buildup of artificial cells based on cell-free
      systems will improve our understanding of life and use them for environmental and
      biomedical applications.

PMID- 29062959
TI  - Evaluation of fermentation conditions triggering increased antibacterial activity
      from a near-shore marine intertidal environment-associated Streptomyces species.
AB  - A near-shore marine intertidal environment-associated Streptomyces isolate (USC
      633) from the Sunshine Coast Region of Queensland, Australia, cultivated under a
      range of chemically defined and complex media to determine optimal parameters
      resulting in the secretion of diverse array of secondary metabolites with
      antimicrobial properties against various antibiotic resistant bacteria. Following
      extraction, fractioning and re-testing of active metabolites resulted in
      persistent antibacterial activity against Escherichia coli (Migula) (ATCC 13706)
      and subsequent Nuclear Magnetic Resonance (NMR) analysis of the active fractions
      confirmed the induction of metabolites different than the ones in fractions which
      did not display activity against the same bacterial species. Overall findings
      again confirmed the value of One Strain-Many Compounds (OSMAC) approach that
      tests a wide range of growth parameters to trigger bioactive compound secretion
      increasing the likelihood of finding novel therapeutic agents. The isolate was
      found to be adaptable to both marine and terrestrial conditions corresponding to
      its original near-shore marine intertidal environment. Wide variations in its
      morphology, sporulation and diffusible pigment production were observed when
      different growth media were used.

PMID- 29062956
TI  - Development of fungal cell factories for the production of secondary metabolites:
      Linking genomics and metabolism.
AB  - The genomic era has revolutionized research on secondary metabolites and
      bioinformatics methods have in recent years revived the antibiotic discovery
      process after decades with only few new active molecules being identified. New
      computational tools are driven by genomics and metabolomics analysis, and enables
      rapid identification of novel secondary metabolites. To translate this increased
      discovery rate into industrial exploitation, it is necessary to integrate
      secondary metabolite pathways in the metabolic engineering process. In this
      review, we will describe the novel advances in discovery of secondary metabolites
      produced by filamentous fungi, highlight the utilization of genome-scale
      metabolic models (GEMs) in the design of fungal cell factories for the production
      of secondary metabolites and review strategies for optimizing secondary
      metabolite production through the construction of high yielding platform cell
      factories.

PMID- 29062960
TI  - Proteome-wide alterations in an industrial clavulanic acid producing strain of
      Streptomyces clavuligerus.
AB  - The usefulness of genetic/metabolic engineering for further improvement of
      industrial strains is subject of discussion because of the general lack of
      knowledge on genetic alterations introduced by iterative cycles of random
      mutagenesis in such strains. An industrial clavulanic acid (CA)-overproducer
      Streptomyces clavuligerus DEPA was assessed to understand proteome-wide changes
      that have occurred in a local industrial CA overproducer developed through
      succesive mutagenesis programs. The proteins that could be identified
      corresponded to 33 distinct ORFs for underrepresented ones and 60 ORFs for
      overrepresented ones. Three CA biosynthetic enzymes were overrepresented in S.
      clavuligerus DEPA; carboxyethylarginine synthase (Ceas2), clavaldehyde
      dehydrogenase (Car) and carboxyethyl-arginine beta-lactam-synthase (Bls2) whereas
      the enzymes of two other secondary metabolites were underrepresented along with
      two important global regulators [two-component system (TCS) response regulator
      (SCLAV_2102) and TetR-family transcriptional regulator (SCLAV_3146)] that might
      be related with CA production and/or differentiation. gamma-butyrolactone
      biosynthetic protein AvaA2 was 2.6 fold underrepresented in S. clavuligerus DEPA.
      The levels of two glycolytic enzymes, 2,3-bisphosphoglycerate-dependent
      phosphoglycerate mutase and phosophoglycerate kinase were found decreased while
      those of dihydrolipoyl dehydrogenase (E3) and isocitrate dehydrogenase, with two
      isoforms were found as significantly increased. A decrease of amino acid
      metabolism, methionine biosynthesis in particular, as well as S
      adenosylmethionine synthetase appeared as one of the prominent mechanisms of
      success of S. clavuligerus DEPA strain as a prolific producer of CA. The levels
      of two enzymes of shikimate pathway that leads to the production of aromatic
      amino acids and aromatic secondary metabolites were also underrepresented. Some
      of the overrepresented stress proteins in S. clavuligerus DEPA included
      polynucleotide phosphorylase/polyadenylase (PNPase), ATP-dependent DNA helicase,
      two isoforms of an anti-sigma factor and thioredoxin reductase. Downregulation of
      important proteins of cell wall synthesis and division was recorded and a protein
      with beta-lactamase domain (SCLAV_p1007) appeared in 12 isoforms, 5 of which were
      drastically overrepresented in DEPA strain. These results described herein
      provide useful information for rational engineering to improve CA production in
      Streptomyces clavuligerus.

PMID- 29062962
TI  - Heterologous expression of Avermectins biosynthetic gene cluster by construction
      of a Bacterial Artificial Chromosome library of the producers.
AB  - Avermectins, a group of polyketide natural products, are widely used as
      anthelmintics in agriculture. Metabolic engineering and combinatorial
      biosynthesis were extensively employed to improve Avermectins production and
      create novel Avermectin derivatives, including Ivermectin and Doramectin. It is
      labor intensive and time cost to genetically manipulate Avermectins producer
      Streptomyces avermitilis in vivo. Cloning and heterologous expression of
      Avermectins biosynthetic gene cluster will make it possible to tailor the cluster
      in vitro. We constructed a Bacterial Artificial Chromosome (BAC) library of S.
      avermitilis ATCC 31267 with inserted DNA fragments ranged from 100 to 130 Kb.
      Five recombinant BAC clones which carried the Avermectins biosynthetic gene
      cluster ave (81 Kb in size) were screened out from the library. Then, ave was
      hetero-expressed in S. lividans. Three Avermectin components, A2a, B1a and A1a
      were detected from the cell extracts of recombinant strains. It will facilitate
      the development of Avermectin derivatives by polyketide synthase domain swapping
      and provide functional element for Avermectins synthetic biology study.

PMID- 29062961
TI  - Novel polysaccharide-protein conjugates provide an immunogenic 13-valent
      pneumococcal conjugate vaccine for S. pneumoniae.
AB  - Pneumonia remains the single leading cause of childhood death worldwide. Despite
      the commercial availability of multiple pneumococcal conjugate vaccines (PCVs),
      high dosage cost and supply shortages prevent PCV delivery to much of the
      developing world. The current work presents high-yield pneumococcal conjugates
      that are immunogenic in animals and suitable for use in human vaccine
      development. The 13-valent pneumococcal conjugate vaccine (PCV-13) investigated
      in this research incorporated serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A,
      19F, and 23F. Pneumococcal polysaccharides (PnPSs) and CRM197 carrier protein
      were produced and purified in-house, and used to prepare PnPS-CRM conjugates
      using unique, cyanide-free, in vacuo glycation conjugation methods. In vitro
      characterization confirmed the generation of higher molecular weight PnPS-CRM
      conjugates low in free protein. In vivo animal studies were performed to compare
      PnuVax's PCV-13 to the commercially available PCV-13, Prevnar(r)13 (Pfizer, USA).
      A boost dose was provided to all groups post-dose 1 at t = 14 days. Post-dose 2
      results at t = 28 days showed that all 13 serotypes in PnuVax's PCV-13 were
      boostable. Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic
      for all 13 serotypes, with 10 of the 13 serotypes statistically the same or
      higher than Prevnar(r)13 post-dose 2. As a result, the novel polysaccharide
      protein conjugates developed in this work are highly promising for use in human
      PCV development. The in vacuo conjugation technique applied in this work could
      also be readily adapted to develop many other conjugate vaccines.

PMID- 29062963
TI  - Modules for in vitro metabolic engineering: Pathway assembly for bio-based
      production of value-added chemicals.
AB  - Bio-based chemical production has drawn attention regarding the realization of a
      sustainable society. In vitro metabolic engineering is one of the methods used
      for the bio-based production of value-added chemicals. This method involves the
      reconstitution of natural or artificial metabolic pathways by assembling
      purified/semi-purified enzymes in vitro. Enzymes from distinct sources can be
      combined to construct desired reaction cascades with fewer biological constraints
      in one vessel, enabling easier pathway design with high modularity. Multiple
      modules have been designed, built, tested, and improved by different groups for
      different purpose. In this review, we focus on these in vitro metabolic
      engineering modules, especially focusing on the carbon metabolism, and present an
      overview of input modules, output modules, and other modules related to cofactor
      management.

PMID- 29062965
TI  - Systems metabolic engineering strategies for the production of amino acids.
AB  - Systems metabolic engineering is a multidisciplinary area that integrates systems
      biology, synthetic biology and evolutionary engineering. It is an efficient
      approach for strain improvement and process optimization, and has been
      successfully applied in the microbial production of various chemicals including
      amino acids. In this review, systems metabolic engineering strategies including
      pathway-focused approaches, systems biology-based approaches, evolutionary
      approaches and their applications in two major amino acid producing
      microorganisms: Corynebacterium glutamicum and Escherichia coli, are summarized.

PMID- 29062967
TI  - Streptophage-mediated control of off-flavour taint producing streptomycetes
      isolated from barramundi ponds.
AB  - Off-flavour taint of aquaculture products is a global issue reducing consumer
      confidence in the farmed produce as they are taken up via the gills of fish, and
      deposited in the lipids of the animal. If the fish are not purged, resulting
      undesirable muddy earthy flavour taint can be tasted by consumers. These
      undesirable flavour and odour is caused by the terpenoid compounds namely geosmin
      and 2-methylisoborneol, produced as secondary metabolites by certain bacteria
      including the cyanobacteria and actinomycetes. Current strategies to remediate
      the problem rely on treating the symptoms not the cause and involve the use of
      time consuming purging methods and costly chemicals. Biological control using
      bacteriophages, specific to the problem causing bacteria, offers a natural
      alternative to chemical control, which might reduce further complications of
      copper based algaecides and its subsequent implications on water quality. In an
      adaptation of such biological control approach streptomycetes isolated from
      barramundi ponds were tested for their susceptibility to streptophages to
      understand whether host destruction via phage lysis would subsequently eliminate
      off-flavour taint productions by these isolates. Following the determination of
      the streptophage susceptibility of the isolates one of the most odourous
      streptomycete species (USC-14510) was selected to be tested further using
      different pond simulations resembling real-life applications. Geosmin was tested
      as the indicator of off-flavour taint production and as it has been previously
      reported that the cyanobacteria-actinomycete interactions occurring in ponds
      result in even greater levels of geosmin and 2-methylisoborneol, the geosmin
      levels for the isolate in the presence of cyanobacteria and streptophages were
      also tested. Findings indicated that the highly odourous Streptomyces species
      (USC-14510) once infected with streptophages, can lose its capacity to produce
      off-flavour taints. Pond simulation studies also revealed geosmin production was
      significantly reduced when streptophages were introduced into the pond water
      where streptomycete species were grown. The bacteriophage control method
      developed in the presented study might again confirm significant potential for
      the bacteriophage-mediated remediation strategy to be adapted by the aquaculture
      industry.

PMID- 29062968
TI  - Systematic assessment of Pichia pastoris system for optimized beta -galactosidase
      production.

PMID- 29062966
TI  - Bacterial cell-free expression technology to in vitro systems engineering and
      optimization.
AB  - Cell-free expression system is a technology for the synthesis of proteins in
      vitro. The system is a platform for several bioengineering projects, e.g. cell
      free metabolic engineering, evolutionary design of experiments, and synthetic
      minimal cell construction. Bacterial cell-free protein synthesis system (CFPS) is
      a robust tool for synthetic biology. The bacteria lysate, the DNA, and the energy
      module, which are the three optimized sub-systems for in vitro protein synthesis,
      compose the integrated system. Currently, an optimized E. coli cell-free
      expression system can produce up to ~2.3 mg/mL of a fluorescent reporter protein.
      Herein, I will describe the features of ATP-regeneration systems for in vitro
      protein synthesis, and I will present a machine-learning experiment for
      optimizing the protein yield of E. coli cell-free protein synthesis systems.
      Moreover, I will introduce experiments on the synthesis of a minimal cell using
      liposomes as dynamic containers, and E. coli cell-free expression system as
      biochemical platform for metabolism and gene expression. CFPS can be further
      integrated with other technologies for novel applications in environmental,
      medical and material science.

PMID- 29062970
TI  - Improvement of pristinamycin I (PI) production in Streptomyces pristinaespiralis
      by metabolic engineering approaches.
AB  - Pristinamycin, produced by Streptomyces pristinaespiralis, which is a
      streptogramin-like antibiotic consisting of two chemically unrelated components:
      pristinamycin I (PI) and pristinamycin II (PII), shows potent activity against
      many antibiotic-resistant pathogens. However, so far pristinamycin production
      titers are still quite low, particularly those of PI. In this study, we
      constructed a PI single component producing strain by deleting the PII
      biosynthetic genes (snaE1 and snaE2). Then, two metabolic engineering approaches,
      including deletion of the repressor gene papR3 and chromosomal integration of an
      extra copy of the PI biosynthetic gene cluster (BGC), were employed to improve PI
      production. The final engineered strain DeltaPIIDeltapapR3/PI produced a maximum
      PI level of 132 mg/L, with an approximately 2.4-fold higher than that of the
      parental strain S. pristinaespiralis HCCB10218. Considering that the PI
      biosynthetic genes are clustered in two main regions in the 210 kb "supercluster"
      containing the PI and PII biosynthetic genes as well as a cryptic polyketide BGC,
      these two regions were cloned separately and then were successfully assembled
      into the PI BGC by the transformation-associated recombination (TAR) system.
      Collectively, the metabolic engineering approaches employed is very efficient for
      strain improvement in order to enhance PI titer.

PMID- 29062969
TI  - Rational synthetic combination genetic devices boosting high temperature ethanol
      fermentation.
AB  - The growth and production of yeast in the industrial fermentation are seriously
      restrained by heat stress and exacerbated by heat induced oxidative stress. In
      this study, a novel synthetic biology approach was developed to globally boost
      the viability and production ability of S. cerevisiae at high temperature through
      rationally designing and combing heat shock protein (HSP) and superoxide
      dismutase (SOD) genetic devices to ultimately synergistically alleviate both heat
      stress and oxidative stress. HSP and SOD from extremophiles were constructed to
      be different genetic devices and they were preliminary screened by heat resistant
      experiments and anti-oxidative experiments, respectively. Then in order to
      customize and further improve thermotolerance of S. cerevisiae, the HSP genetic
      device and SOD genetic device were rationally combined. The results show the
      simply assemble of the same function genetic devices to solve heat stress or
      oxidative stress could not enhance the thermotolerance considerably. Only S.
      cerevisiae with the combination genetic device (FBA1p-sod-MB4-FBA1p-shsp-HB8)
      solving both stress showed 250% better thermotolerance than the control and
      displayed further 55% enhanced cell density compared with the strains with single
      FBA1p-sod-MB4 or FBA1p-shsp-HB8 at 42  degrees C. Then the most excellent
      combination genetic device was introduced into lab S. cerevisiae and industrial
      S. cerevisiae for ethanol fermentation. The ethanol yields of the two strains
      were increased by 20.6% and 26.3% compared with the control under high
      temperature, respectively. These results indicate synergistically defensing both
      heat stress and oxidative stress is absolutely necessary to enhance the
      thermotolerance and production of S. cerevisiae.

PMID- 29062964
TI  - Targeted mutagenesis: A sniper-like diversity generator in microbial engineering.
AB  - Mutations, serving as the raw materials of evolution, have been extensively
      utilized to increase the chances of engineering molecules or microbes with tailor
      made functions. Global and targeted mutagenesis are two main methods of obtaining
      various mutations, distinguished by the range of action they can cover. While the
      former one stresses the mining of novel genetic loci within the whole genomic
      background, targeted mutagenesis performs in a more straightforward manner,
      bringing evolutionary escape and error catastrophe under control. In this review,
      we classify the existing techniques of targeted mutagenesis into two categories
      in terms of whether the diversity is generated in vitro or in vivo, and briefly
      introduce the mechanisms and applications of them separately. The inherent
      connections and development trends of the two classes are also discussed to
      provide an insight into the next generation evolution research.

PMID- 29062972
TI  - Electrochemical impedance spectroscopy measurements for determination of
      derivatized aldehydes in several matrices.
AB  - A simple, selective and sensitive electrochemical method is described for the
      determination of different aldehydes at glassy carbon electrode using
      electrochemical impedance spectroscopy (EIS). The measurements were performed
      after their derivatization with 2,4-dinitrophenylhydrazine (DNPH) in acidic
      medium. The impedance measurements were investigated in the frequency range from
      100 mHz to 100 kHz at a potential of 1.0 V versus Ag/AgCl. The Nyquist plots were
      modeled with a Randle's equivalent circuit. The charge transfer resistance was
      identified as the dependent parameter on relevant concentration of aldehydes
      (determined as their hydrazones). Under the optimized conditions, the linearity
      was established over the concentration range of 1000-0.05 MUmol L-1. The limits
      of detection (LODs) obtained were from 0.097 to 0.0109 MUmol L-1. Finally, the
      developed method has been applied to the determination of aldehydes in drinking
      water, orange juice and apple vinegar samples with relative standard deviations
      (RSDs) < 3.1% and acceptable recovery rate (around of 80%).

PMID- 29062971
TI  - Characterization of the metallo-dependent amidohydrolases responsible for
      "auxiliary" leucinyl removal in the biosynthesis of 2,2'-bipyridine antibiotics.
AB  - 2,2'-Bipyridine (2,2'-BiPy) is an attractive core structure present in a number
      of biologically active natural products, including the structurally related
      antibiotics caerulomycins (CAEs) and collismycins (COLs). Their biosynthetic
      pathways share a similar key 2,2'-BiPy-l-leucine intermediate, which is
      desulfurated or sulfurated at C5, arises from a polyketide synthase/nonribosomal
      peptide synthetase hybrid assembly line. Focusing on the common off-line
      modification steps, we here report that the removal of the "auxiliary" l-leucine
      residue relies on the metallo-dependent amidohydrolase activity of CaeD or ColD.
      This activity leads to the production of similar 2,2'-BiPy carboxylate products
      that then receive an oxime functionality that is characteristic for both CAEs and
      COLs. Unlike many metallo-dependent amidohydrolase superfamily proteins that have
      been previously reported, these proteins (particularly CaeD) exhibited a strong
      zinc ion-binding capacity that was proven by site-specific mutagenesis studies to
      be essential to proteolytic activity. The kinetics of the conversions that
      respectively involve CaeD and ColD were analyzed, showing the differences in the
      efficiency and substrate specificity of these two proteins. These findings would
      generate interest in the metallo-dependent amidohydrolase superfamily proteins
      that are involved in the biosynthesis of bioactive natural products.

PMID- 29062974
TI  - Metatranscriptomic and metagenomic description of the bacterial nitrogen
      metabolism in waste water wet oxidation effluents.
AB  - Anaerobic digestion is a common method for reducing the amount of sludge solids
      in used waters and enabling biogas production. The wet oxidation process (WOX)
      improves anaerobic digestion by converting carbon into methane through oxidation
      of organic compounds. WOX produces effluents rich in ammonia, which must be
      removed to maintain the activity of methanogens. Ammonia removal from WOX could
      be biologically operated by aerobic granules. To this end, granulation
      experiments were conducted in 2 bioreactors containing an activated sludge (AS).
      For the first time, the dynamics of the microbial community structure and the
      expression levels of 7 enzymes of the nitrogen metabolism in such active
      microbial communities were followed in regard to time by metagenomics and
      metatranscriptomics. It was shown that bacterial communities adapt to the wet
      oxidation effluent by increasing the expression level of the nitrogen metabolism,
      suggesting that these biological activities could be a less costly alternative
      for the elimination of ammonia, resulting in a reduction of the use of chemicals
      and energy consumption in sewage plants. This study reached a strong sequencing
      depth (from 4.4 to 7.6 Gb) and enlightened a yet unknown diversity of the
      microorganisms involved in the nitrogen pathway. Moreover, this approach revealed
      the abundance and expression levels of specialised enzymes involved in
      nitrification, denitrification, ammonification, dissimilatory nitrate reduction
      to ammonium (DNRA) and nitrogen fixation processes in AS.

PMID- 29062973
TI  - Microscopic dissipative structuring and proliferation at the origin of life.
AB  - Some fundamental molecules of life are suggested to have been formed,
      proliferated, and evolved through photochemical microscopic dissipative
      structuring and autocatalytic proliferation under the UV-C/UV-B solar environment
      prevalent at Earth's surface throughout the Archean. Evidence is given in the
      numerous salient characteristics of these, including their strong absorption in
      this spectral region and their rapid non-radiative excited state decay through
      inherent conical intersections. The examples of the dissipative structuring and
      dissipative proliferation of the purines and of single strand DNA are given. UV-C
      and UV-B-induced stationary state isomerizations and tautomerizations are shown
      to be crucial to the formation of the purines from hydrogen cyanide in an aqueous
      environment under UV-C light, while UV-C induced phosphorylation of nucleosides
      and denaturing of double helix RNA and DNA are similarly important to the
      production and proliferation of single strand DNA. This thermodynamic dissipation
      perspective provides a physical-chemical foundation for understanding the origin
      and evolution of life.

PMID- 29062975
TI  - A placebo-controlled Bayesian dose finding design based on continuous
      reassessment method with application to stroke research.
AB  - Traditional dose-finding designs do not require assignment of patients to a
      control group. Motivated by SHRINC (Safety of Pioglitazone for hematoma
      resolution in intracerebral hemorrhage), we developed a placebo-controlled dose
      finding study to identify the maximum tolerated dose for pioglitazone in stroke
      patients with spontaneous intracerebral hemorrhage. We designed an extension of
      the continuous reassessment method that allowed to incorporate information from
      the control group (i.e., the standard of care), and utilized it to determine the
      maximum tolerated dose in the SHRINC trial. We evaluated the operating
      characteristics of our design by conducting extensive simulation studies. Our
      findings from the simulation studies demonstrate that our proposed design is
      robust and performs well. By estimating the toxicity rate in the control group,
      we were able to obtain more accurate information about the natural history of the
      disease and identify appropriate dose for the next phase of this study. The
      proposed design provides a tool to incorporate the information from the control
      group into the dose-finding framework for trials with similar objectives.

PMID- 29062976
TI  - Recent progress and open challenges in modeling p53 dynamics in single cells.
AB  - In mammalian cells, the tumor suppressor p53 is activated upon a variety of
      cellular stresses and ensures an appropriate response ranging from arrest and
      repair to the induction of senescence and apoptosis. Quantitative measurements in
      individual living cells showed stimulus-dependent dynamics of p53 accumulation
      upon stress induction. Due to the complexity of the underlying biochemical
      interactions, mathematical models were indispensable for understanding the
      topology of the network regulating p53 dynamics. Recent work provides furhter
      insights into the causes of heterogeneous responses in individual cells, the
      rewiring of the network in response to different inputs and the role of the
      downstream processes in determining the cellular fate upon stress.

PMID- 29062977
TI  - Expansion Mini-Microscopy: An Enabling Alternative in Point-of-Care Diagnostics.
AB  - Diagnostics play a significant role in health care. In the developing world and
      low-resource regions the utility for point-of-care (POC) diagnostics becomes even
      greater. This need has long been recognized, and diagnostic technology has seen
      tremendous progress with the development of portable instrumentation such as
      miniature imagers featuring low complexity and cost. However, such inexpensive
      devices have not been able to achieve a resolution sufficient for POC detection
      of pathogens at very small scales, such as single-cell parasites, bacteria,
      fungi, and viruses. To this end, expansion microscopy (ExM) is a recently
      developed technique that, by physically expanding preserved biological specimens
      through a chemical process, enables super-resolution imaging on conventional
      microscopes and improves imaging resolution of a given microscope without the
      need to modify the existing microscope hardware. Here we review recent advances
      in ExM and portable imagers, respectively, and discuss the rational combination
      of the two technologies, that we term expansion mini-microscopy (ExMM). In ExMM,
      the physical expansion of a biological sample followed by imaging on a mini
      microscope achieves a resolution as high as that attainable by conventional high
      end microscopes imaging non-expanded samples, at significant reduction in cost.
      We believe that this newly developed ExMM technique is likely to find widespread
      applications in POC diagnostics in resource-limited and remote regions by
      expanded-scale imaging of biological specimens that are otherwise not resolvable
      using low-cost imagers.

PMID- 29062979
TI  - Launch of a new journal, beginning of a new era.

PMID- 29062981
TI  - Primary osteoporosis in postmenopausal women.

PMID- 29062982
TI  - Clinical significance of intratumor heterogeneity for gynecological carcinoma.

PMID- 29062980
TI  - Current status of breast cancer prevention in China.

PMID- 29062983
TI  - Tumor necrosis factor-alpha and its role as a mediator in myocardial infarction:
      A brief review.
AB  - Tumor necrosis factor-alpha (TNF-alpha) contributes to myocardial infarction (MI)
      injury. Polymorphism of TNF-alpha gene promoter region and secretion and release
      of TNF-alpha and its transformation by a series of signaling pathways are all
      changed at different points of pathophysiological process in MI. Researches also
      investigated TNF-alpha antagonists and their potential therapeutic role in the
      setting of MI and heart failure at both molecular and clinical level. This
      article briefly reviews TNF-alpha and its mechanism as a mediator in MI.

PMID- 29062985
TI  - Soluble CD40 in plasma and malignant pleural effusion with non-small cell lung
      cancer: A potential marker of prognosis.
AB  - OBJECTIVE: Soluble CD40 (sCD40) is a potential modulator for both antitumor
      responses and CD40-based immunotherapy; however the levels and significance of
      sCD40 in non-small cell lung cancer (NSCLC) patients with malignant pleural
      effusion are unknown. METHODS: Forty-eight patients with lung cancer were treated
      in our institutions from January 2008 to January 2010. Peripheral blood and
      pleural effusion samples were collected from each subject. sCD40 levels in plasma
      and malignant pleural effusions supernatant were measured. The CD40L expression
      on CD3t T-cells was confirmed by flow cytometric direct immunofluorescence
      analysis. All patients were followed up after the study ended on January 1, 2010.
      RESULTS: Patients with malignant pleural effusion of NSCLC had elevated
      circulating and pleural effusion levels of sCD40, and these elevated sCD40 levels
      were associated with advanced diseases and a poor prognosis. CONCLUSIONS: These
      findings indicate that elevated sCD40 may have a role in modulating antitumor
      responses and may also be a useful prognostic marker.

PMID- 29062986
TI  - Cultural adaptation of the Michigan Hand Outcomes Questionnaire in patients with
      Carpal Tunnel Syndrome: A Turkish version study.
AB  - OBJECTIVE: Cultural adaptations of the questionnaires are important for easy use.
      We aimed to assess the reliability and validity of the Turkish Version of the
      Michigan Hand Outcomes Questionnaire in patients with Carpal Tunnel Syndrome.
      METHODS: To assess test-retest reliability, the Turkish "Michigan Hand Outcomes
      Questionnaire" and "Disabilities of Arm, Shoulder and Hand" questionnaires were
      answered by patients and controls and were repeated a week later. For testing
      internal consistency, the Cronbach's alpha test was used. For testing validity,
      correlations between the subscales of the "Michigan Hand Outcomes Questionnaire"
      and "Disabilities of Arm, Shoulder and Hand" questionnaire were measured in
      patient groups. One hundred patients with idiopathic Carpal Tunnel Syndrome and
      50 healthy participants were included in the study. RESULTS: In test-retest
      reliability, intraclass correlations of the subscales of the "Michigan Hand
      Outcomes Questionnaire" were high. Cronbach's alphas were found to be high in all
      subscales. There was no significant correlation between asthetics and pain
      scales. We found significant differences between patients and controls regarding
      all subscales of the "Michigan Hand Outcomes Questionnaire". Correlations between
      subscales of the "Michigan Hand Outcomes Questionnaire" and "Disabilities of Arm,
      Shoulder and Hand" questionnaire were significant. We found no difference between
      one-hand effected and two-hand effected patients, in terms of the "Michigan Hand
      Outcomes Questionnaire", "Disabilities of Arm, Shoulder and Hand" questionnaire
      Function/Symptom and Work average scores. CONCLUSION: This study showed that the
      Turkish version of the "Michigan Hand Outcomes Questionnaire" is reliable and
      valid and can be used in Turkish patients with Carpal Tunnel Syndrome because it
      is comprehensible and practicable.

PMID- 29062984
TI  - Potential role of pemetrexed in metastatic breast cancer patients pre-treated
      with anthracycline or taxane.
AB  - OBJECTIVES: This article reviews pharmacology, pharmacokinetic properties,
      clinical efficacy, and safety in metastatic breast cancer patients, as well as
      the predictive biomarkers for outcome of treatment with pemetrexed-based
      regimens. METHODS: PubMed, Embase, OVID, and the Cochrane Library databases were
      searched from the beginning of each database without any limitations to the date
      of publication. Search terms were ''pemetrexed'' or ''LY231514'' or "Alimta",
      "metastatic breast cancer", and "advanced breast cancer". RESULTS: There were 15
      studies (n = 1002) meeting our criteria for evaluation. Eight single-agent trials
      (n = 551) and seven using combinations with other agents (n = 451) were
      identified that evaluated pemetrexed for use in patients with metastatic breast
      cancer. Response rates to pemetrexed as a single agent varied from 8% to 31%, and
      with combination therapy have been reported to be between 15.8% and 55.7%. With
      routine supplementation of patients with folic acid, dexamethasone, and vitamin
      B12, the toxicity profile of these patients was mild, including dose-limiting
      neutropenia and thrombocytopenia, as well as lower grades of reversible
      hepatotoxicity and gastrointestinal toxicity. Expression of thymidylate synthase
      (TS) and other biomarkers are associated with the prognosis and sensitivity for
      pemetrexed in breast cancer. CONCLUSION: Pemetrexed has shown remarkable activity
      with acceptable toxicities for treatment of metastatic breast cancer patients.
      Translational research on pemetrexed in breast cancer identified biomarkers as
      well as additional genes important to its clinical activity and toxicity. Further
      research is needed to clarify the role of pemetrexed in breast cancer treatment
      in order to guide oncologists.

PMID- 29062978
TI  - INTERNEURONOPATHIES AND THEIR ROLE IN EARLY LIFE EPILEPSIES AND
      NEURODEVELOPMENTAL DISORDERS.
AB  - GABAergic interneurons control the neural circuitry and network activity in the
      brain. The advances in genetics have identified genes that control the
      development, maturation and integration of GABAergic interneurons and implicated
      them in the pathogenesis of epileptic encephalopathies or neurodevelopmental
      disorders. For example, mutations of the Aristaless-Related homeobox X-linked
      gene (ARX) may result in defective GABAergic interneuronal migration in infants
      with epileptic encephalopathies like West syndrome (WS), Ohtahara syndrome or X
      linked lissencephaly with abnormal genitalia (XLAG). The concept of
      "interneuronopathy", i.e. impaired development, migration or function of
      interneurons, has emerged as a possible etiopathogenic mechanism for epileptic
      encephalopathies. Treatments that enhance GABA levels, may help seizure control
      but do not necessarily show disease modifying effect. On the other hand,
      interneuronopathies can be seen in other conditions in which epilepsy may not be
      the primary manifestation, such as autism. In this review, we plan to outline
      briefly the current state of knowledge on the origin, development, and migration
      and integration of GABAergic interneurons, present neurodevelopmental conditions,
      with or without epilepsy, that have been associated with interneuronopathies and
      discuss the evidence linking certain types of interneuronal dysfunction with
      epilepsy and/or cognitive or behavioral deficits.

PMID- 29062987
TI  - Is there a role for B lymphocyte chimerism in the monitoring of B-acute
      lymphoblastic leukemia patients receiving allogeneic stem cell transplantation?
AB  - OBJECTIVE: To determine the sensitivity and significance of B-cell chimerism for
      the detection of early engraftment, transplant rejection, and disease relapse.
      METHODS: The dynamic monitoring of lineage-specific cell subtypes (B, T, and NK
      cells) was made in 20 B-cell acute lymphoblastic leukemia (B-ALL) patients
      following allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the
      early period after allo-HSCT, the latest establishment of B-cell complete
      chimerism (CC) was observed in a majority of patients. RESULTS: The percentage of
      donor cells of B-cell lineage was lower than the percent of T-cell lineage in
      most of the mixed chimerism (MC) patients. During graft rejection, the frequency
      of patients with decreasing MC of B-, T- and NK-cell lineage were 5/5, 2/5, and
      2/5. When disease relapsed, five patients showed a faster decrease of the donor
      percent of B-cells than of T- or NK-cells. Only one patient displayed a more
      rapid decrease in NK-cells than in T- or B-cells. CONCLUSION: Monitoring of B
      cell chimerism after HSCT seems to be valuable for insuring complete engraftment,
      anticipating graft rejection, and relapse in B-ALL patients.

PMID- 29062988
TI  - Coil closure of lumbar artery pseudoaneurysm: An unusual complication associated
      with anomalous left circumflex artery primary percutaneous coronary intervention.

PMID- 29062989
TI  - Screening for candidate genes related to breast cancer with cDNA microarray
      analysis.
AB  - OBJECTIVE: The aim of this study was to reveal the exact changes during the
      occurrence of breast cancer to explore significant new and promising genes or
      factors related to this disease. METHODS: We compared the gene expression
      profiles of breast cancer tissues with its uninvolved normal breast tissues as
      controls using the cDNA microarray analysis in seven breast cancer patients.
      Further, one representative gene, named IFI30, was quantitatively analyzed by
      real-time PCR to confirm the result of the cDNA microarray analysis. RESULTS: A
      total of 427 genes were identified with significantly differential expression,
      221 genes were up-regulated and 206 genes were down-regulated. And the result of
      cDNA microarray analysis was validated by detection of IFI30 mRNA level changes
      by real-time PCR. Genes for cell proliferation, cell cycle, cell division,
      mitosis, apoptosis, and immune response were enriched in the up-regulated genes,
      while genes for cell adhesion, proteolysis, and transport were significantly
      enriched in the down-regulated genes in breast cancer tissues compared with
      normal breast tissues by a gene ontology analysis. CONCLUSION: Our present study
      revealed a range of differentially expressed genes between breast cancer tissues
      and normal breast tissues, and provide candidate genes for further study focusing
      on the pathogenesis and new biomarkers for breast cancer.

PMID- 29062990
TI  - Balloon-expanding stent and delivery system for transcatheter aortic valve
      implantation: An animal study.
AB  - OBJECTIVE: To evaluate the feasibility and satefy of transcatheter aortic valve
      implantation in animals by using a new balloon-expanding valved stent. METHODS:
      The balloon-expandable stent is made from cobalt-based alloy material and
      designed with a tubular, slotted structure. Fresh bovine pericardium was treated,
      sutured and fixed on the balloon-expandable stent. Ten healthy sheep (five males
      and five females), weighing an average of (25.16 +/- 1.83) kg, were selected to
      undergo transcatheter implantation of the valve stents. The function of the valve
      stent was evaluated by angiography, echocardiography, and histology six months
      after the procedure. RESULTS: Of the ten experimental sheep, two sheep died
      during the operation because the higher position of the artificial valve affected
      the opening of the coronary artery. We successfully implanted the aortic valve
      stent in other eight sheep; however, one sheep died of heart failure two weeks
      after the operation due to the lower position of the valve stent. The valve
      stents were implanted in the desired position in seven sheep. Ascending aortic
      angiographic and autoptic findings immediately after the operation confirmed the
      satisfactory location and function of the valved stent. Echocardiography,
      angiography, and histology at six postoperative months confirmed the satisfactory
      location and function of the valve stent. CONCLUSION: We successfully implanted
      our new valve stent as a replacement of native aortic valve via the transcatheter
      route with satisfactory outcome.

PMID- 29062992
TI  - Comparison of circumferential pulmonary vein anatomy mapping guided by 3D mapping
      versus a mesh mapping catheter.
AB  - OBJECTIVE: Catheter-based pulmonary vein isolation (PVI) is an established
      therapy for paroxysmal atrial fibrillation. The high-density mesh mapper (HDMM)
      guides circumferential PV-atrium isolation without the 3D electroanatomic
      mapping. This study aims to compare circumferential pulmonary vein (CPV) anatomy
      mapping between guiding by a 3D mapping system and the HDMM. METHODS: Forty-four
      consecutive patients with paroxysmal atrial fibrillation were scheduled for a
      first procedure for PVI. A CPV ostial anatomy map guided by HDMM was set up in
      the CARTO system while the operator was blinded to the CARTO screen. Then CARTO
      guided ipsilateral PV maps were obtained and PVI was performed. This established
      another set of CPV ostial anatomy maps. The differences between the two mapping
      images were compared and analyzed. RESULTS: All 176 PVs in 44 patients could be
      mapped by both HDMM and CARTO. About 44.9% of the PV ostial anatomies were
      generally similar between the two different map images. The average point-to
      point straight distance between the HDMM-guided map and the CARTO-guided map was
      6.2 +/- 1.4 mm. The area of the circumferential right PV (CRPV) in the HDMM map
      was larger than that in the CARTO map (P = 0.013). After a mean follow-up of 18.3
      +/- 4.3 months (6-24 months), 72.7% of patients (32/44) were free of atrial
      arrhythmia without anti-arrhythmic drugs (AADs). CONCLUSION: Compared to the
      CARTO-guided CPV anatomy image, a highly similar figure could be achieved by
      mapping guided by the HDMM. (Clinical trial.gov number, ChiCTR-TNRC-11001390.).

PMID- 29062991
TI  - Influence of Tirofiban maintenance duration on patients with acute myocardial
      infarction treated by percutaneous coronary intervention.
AB  - OBJECTIVE: To evaluate the efficacy and short term prognosis of Tirofiban in
      different treatment duration in patients with acute ST segment elevation
      myocardial infarction (STEMI) and percutaneous coronary intervention (PCI)
      combined with intracoronary injection. METHODS: A total of 125 patients with
      acute STEMI were enrolled in this study. They were randomly divided into two
      groups: control group (n = 61) and Tirofiban group (n = 64). The Tirofiban was
      used by intracoronary and intravenous administration in Tirofiban group which was
      randomly divided into three sub-groups according to the duration of Tirofiban by
      persistent intravenous injection for 12 hours, 24 hours or 36 hours. Thrombolysis
      in myocardial infarction flow and myocardial perfusion grades were recorded
      immediately after PCI. The adverse cardiac events and cardiac death within 180
      days of PCI, and the adverse effects (hemorrhage and thrombocytopenia) were
      compared between the two groups and within Tirofiban sub-groups. RESULTS: Grade 3
      in myocardial perfusion was significantly better in Tirofiban group than control
      group (85.94% vs. 72.13%, P = 0.03) after PCI. There was one cardiac death in
      control group in 180 days after PCI. The adverse cardiac event rates between two
      groups was significant difference (16 patients in control group and only 8 in
      Tirofiban group, P = 0.047). There was no significant difference in incidence of
      hemorrhage complications and platelet counts between two groups. Nevertheless,
      hemorrhage complications in the 12- and 24-hour subgroups were less than 36-hour
      subgroup (P = 0.01). CONCLUSIONS: Intravenous Tirofiban treatment reduced the
      adverse cardiac events and improved short term prognosis without increasing the
      adverse reactions of the drugs in patients undergoing PCI. The less rate of
      hemorrhage complication can be achieved in short-duration of Tirofiban by
      intravenous injection after PCI.

PMID- 29062993
TI  - Decrease with aging of the microcirculatory function of the lumbar vertebral
      marrow preceding the loss of bone material density and the onset of
      intervertebral discal degeneration: A study about the potential cause.
AB  - OBJECTIVE: Using a dynamic computed tomographic perfusion (CTP) imaging method to
      explore the age-related distribution of the microcirculation perfusion function
      in the vertebral marrow, the bone material density (BMD), and the intervertebral
      discal degeneration (IDD). Further, to discuss a possible causation relationship
      between them. METHODS: One hundred and eighty-six people were randomly enrolled
      by stratified sampling and grouped by age: <=15, 16-25, 26-35, 36-45, 46-55, 56
      65, 66-75, and >=76 years old. The average CTP and BMD of the third and fourth
      lumbar vertebrae marrow were measured and the IDD incidence of the third-fourth
      vertebrae was assessed. The temporal-spatial distribution patterns of the age
      related changes of the CTP, BMD, and IDD were described, and the correlations
      between them were calculated. RESULTS: The microcirculatory perfusion function of
      the vertebral marrow develops to maturity by 25 years and is maintained until age
      35, then declines with aging. The BMD grew to a peak from 26 to 45 years old,
      then decreased yearly. The IDD showed a sudden increase after 45 years of age.
      The CTP [BF (r = 0.806, P = 0.000), BV (r = 0.685, P = 0.005) and PMB (r = 0.619,
      P = 0.001)] showed strong positive correlations and CTP [TTP (r = -0.211, P =
      0.322) and MTT (r = -0.598, P = 0.002)] showed negative correlations with BMD.
      The CTP [BF (r = -0.815, P = 0.000), BV (r = -0.753, P = 0.000) and PMB (r = 
      0.690, P = 0.000)] had strong negative correlations, and CTP [TTP (r = 0.323, P =
      0.126) and MTT (r = 0.628, P = 0.001)] had positive correlations with the
      incidence of IDD. CONCLUSION: The decrease with aging of the microcirculatory
      perfusion in the lumbar vertebral marrow preceded, and is a potential causative
      factor for the loss of BMD and the onset of IDD.

PMID- 29062994
TI  - Study on the correlation between the concentration of plasma lipoprotein
      associated phospholipase A2 and coronary heart disease.
AB  - OBJECTIVE: This study explores the correlation between plasma lipoprotein
      associated phospholipase A2 (Lp-PLA2) and coronary heart disease (CHD) by
      comparing the level of plasma Lp-PLA2 in the plasma of patients with different
      types of CHD. METHODS: Blood samples were collected from 56 patients diagnosed
      with CHD by the Department of Cardiology of the First People's Hospital of Foshan
      and 34 healthy subjects from February 2013 to January 2014. We measured the
      concentration of plasma Lp-PLA2 and determined the levels of total cholesterol
      (Tch), triglyceride (TG), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B),
      high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol
      (LDL-c), lipoprotein a (Lp(a)), glucose (Glu), and high-sensitivity C-reactive
      protein (hs-CRP). The concentration of plasma Lp-PLA2 in the healthy control
      group and each subgroup of CHD patients were compared and analyzed for
      correlations of plasma Lp-PLA2 between the patients in different CHD subgroups
      and several laboratory indicators. RESULTS: The concentration of plasma Lp-PLA2
      in each subgroup of CHD was significantly higher than in the control group (P <
      0.05). The concentration of Lp-PLA2 in the unstable angina pectoris (UAP) group
      and acute myocardial infarction (AMI) group were significantly higher than in the
      stable angina pectoris (SAP) group (P < 0.05), and the concentration of plasma Lp
      PLA2 in the AMI group was significantly higher than in the UAP group (P < 0.05).
      The concentration of plasma Lp-PLA2 in the CHD group merely showed a positive
      correlation (r = 0.493, P < 0.05) with the hs-CRP group, but the levels of Tch,
      TG, Apo-A1, Apo-B, HDL-c, LDL-c, Lp(a) and Glu did not. CONCLUSIONS: The
      concentration of plasma Lp-PLA2 in patients with CHD was higher than that in the
      control group. The concentration of plasma Lp-PLA2 in the subgroups of CHD
      patients varied greatly from each other. The inflammatory response of
      atherosclerosis might be resulted from the synergy of plasma Lp-PLA2 and hs-CRP.

PMID- 29062995
TI  - Detection of respiratory viral and bacterial pathogens causing pediatric
      community-acquired pneumonia in Beijing using real-time PCR.
AB  - OBJECTIVE: The aim of this study was to determine the etiology and prevalence of
      pediatric CAP in Beijing using a real-time polymerase chain reaction (PCR)
      technique. METHODS: Between February 15, 2011 and January 18, 2012, 371 pediatric
      patients with CAP were enrolled at Beijing Children's Hospital. Sixteen
      respiratory viruses and two bacteria were detected from tracheal aspirate
      specimens using commercially available multiplex real-time reverse transcription
      PCR (RT-PCR) kits. RESULTS: A single viral pathogen was detected in 35.3% of
      enrolled patients, multiple viruses in 11.6%, and virus/bacteria coinfection in
      17.8%. In contrast, only 6.5% of patients had a single bacterial pathogen and
      2.2% were infected with multiple bacteria. The etiological agent was unknown for
      26.7% of patients. The most common viruses were respiratory syncytial virus (RSV)
      (43.9%), rhinovirus (14.8%), parainfluenza virus (9.4%), and adenovirus (8.6%).
      In patients under three years of age, RSV (44.6%), rhinovirus (12.8%), and
      Streptococcus pneumoniae (9.9%) were the most frequent pathogens. In children
      aged 3-7 years, S. pneumoniae (38.9%), RSV (30.6%), Haemophilus influenzae
      (19.4%), and adenovirus (19.4%) were most prevalent. Finally in children over
      seven years, RSV (47.3%), S. pneumoniae (41.9%), and rhinovirus (21.5%)
      infections were most frequent. CONCLUSIONS: Viral pathogens, specifically RSV,
      were responsible for the majority of CAP in pediatric patients. However, both S.
      pneumoniae and H. influenzae contributed as major causes of disease. Commercially
      available multiplexing real-time PCR allowed for rapid detection of the
      etiological agent.

PMID- 29062996
TI  - A questionnaire survey on the management of Graves' orbitopathy in China: A
      comparison with Europe and Latin-America.
AB  - OBJECTIVE: Management of Graves' orbitopathy (GO) continues to be a challenge to
      clinical endocrinologists. In the last few years, surveys on GO management have
      succeeded in elucidating trends in Europe and Latin America. To determine how
      endocrinologists in China assess and treat patients with GO and gain insight into
      how to make the management of this disease more uniform and standardized.
      METHODS: Based on the questionnaire used in the European survey on GO, a
      questionnaire in China was drafted and circulated to the members of Chinese
      Society of Endocrinology (CSE) during the annual meeting. RESULTS: A total of 124
      valid responses were analysed. Almost all respondents (94.4%) claimed that a
      multidisciplinary approach for GO management was valuable. Over 80% of the
      participants advocated the assessment of exophthalmometry, vision, visual fields
      by perimetry, eye movements, and fundoscopy. Glucocorticoids were preferred as
      the first-line therapy by 92.7% of respondents, among them, 59.7% choose the
      intravenous route. The treatment strategy for GO with intravenous glucocorticoids
      therapy still remains debatable. Anti-thyroid drugs (ATDs) were the most common
      choice (72.6%) for first-line therapy of coexisting hyperthyroidism. Treatment
      options for GO were very similar among Chinese, Latin-American and European
      respondents, whereas radioactive iodine and surgical treatment were more often
      indicated for co-existing hyperthyroidism in China. CONCLUSION: The appropriate
      treatment for patients with GO is controversial even among thyroid specialists.
      Further training of thyroid specialists, easier access of patients to
      multidisciplinary centres and establishment of practice guidelines are required
      for the management of this condition in China.

PMID- 29062998
TI  - Community-based integration of management of non-communicable diseases in China.
AB  - Non-communicable diseases (NCDs) are a leading cause of deaths and of disease
      burden in China. This paper analyzes the rationale and implications of a
      community-based approach to a better coordinated NCDs care and management system
      in China. As argued by the author, the buildup of an integrated NCDs care
      delivery system is feasible now and large health expenditures will be saved if
      more stable outpatients with NCDs could be shifted to community health facilities
      to receive their medications. However, the key issues remain in building a
      general practitioner led (GP-led) primary care delivery system in China. Some
      prominent issues include the shortage of quality generalists, lack of proper
      incentives and management mechanisms, and the absence of patients and provider,
      and restrictive arrangements in basic health insurance policies. Even with these
      hard-to-solve issues, some recent reform initiatives for integrated NCDs care
      delivery in some localities have demonstrated originality and creativeness in
      developing better coordination between primary and secondary NCDs care. However,
      without large-scale public sector reform, innate issues with human resource
      development, income distribution and financing of public healthcare providers
      cannot be solved. It may take a long time to see deep integration of primary and
      secondary NCDs care in China.

PMID- 29062997
TI  - Impact of elevated aspartate and alanine aminotransferase on metabolic syndrome
      and its components among adult people living in Ningxia, China.
AB  - OBJECTIVE: Metabolic syndrome (MS) is a combination of medical disorders that
      increase the risk for cardiovascular disease and diabetes mellitus. It suggests
      an association between an elevated serum aminotransferase level and MS. Little
      data show the relationship between the levels of serum aminotransferase and the
      incidence of MS in Ningxia, China. METHODS: A total of 5415 subjects who received
      medical health checkups from 2007 to 2009 were enrolled in the study. The
      participants were interviewed by trained health workers under a structured
      questionnaire. MS was defined according to the modified ATPIII criteria for Asian
      Americans by the American Heart Association (AHA-ATP III). RESULTS: The
      prevalence of elevated aspartate aminotransferase (AST) and ALT (>40 U/L) were
      7.1% and 22.2% in males, and 2.1% and 4.8% in females respectively. The
      prevalence of MS was 32.1% in males and 15.4% in females. The components of MS
      were significantly more in the group with elevated aminotransferase levels than
      in the group with normal aminotransferase levels. The odds ratios (95% CI) for
      elevated AST were 1.90 (1.49, 2.42), 2.59 (2.01, 3.39), 1.68 (1.32, 2.15), and
      1.81 (1.36, 2.42) in the adults with abdominal obesity, high serum triglycerides
      levels, high blood pressure, and high plasma glucose levels respectively. After
      adjustment for age, the odds ratios (95% CI) for elevated ALT were 3.08 (2.63,
      3.61), 4.30 (3.64, 5.08), 1.26 (1.08, 1.48), 2.16 (1.93, 2.65) and 2.38 (1.96,
      2.87) in adults with abdominal obesity, high serum triglycerides levels, low
      serum high-density lipoproteincholesterol (HDL-C), high blood pressure, and high
      plasma glucose levels respectively. The odds ratios (95% CI) for elevated AST
      were 1.67 (1.06, 2.63), 2.28 (1.46, 3.63), 2.59 (1.59, 4.21) and for elevated ALT
      2.02 (1.50, 2.73), 2.68 (1.96, 3.65), 3.94 (2.86, 5.43) for the subjects with 1,
      2, and >=3 risk factors after adjustment for age, gender, and BMI. CONCLUSION:
      The serum aminotransferase levels were higher in males compared to females, and
      serum ALT level was more closely associated with MS than the AST level in adults
      in Ningxia, China. With an increasing the number of components of MS, the
      aminotransferase levels and the risks for elevated aminotransferase increase,
      whereas the AST/ALT ratios decrease.

PMID- 29062999
TI  - Comprehensive understanding of developmental origins of health and disease
      concepts: Early intervention to non-communicable diseases in China.

PMID- 29063000
TI  - The "expert patient" approach for non-communicable disease management in low and
      middle income settings: When the reality confronts the rhetoric.
AB  - This paper seeks to explore the relevance between the Western "expert patient"
      rhetoric and the reality of non-communicable diseases (NCDs) control and
      management in low and middle income settings from the health sociological
      perspective. It firstly sets up a conceptual framework of the "expert patient" or
      the patient self-management approach, showing the rhetoric of the initiative in
      the developed countries. Then by examining the situation of NCDs control and
      management in low income settings, the paper tries to evaluate the possibilities
      of implementing the "expert patient" approach in these countries. Kober and Van
      Damme's study on the relevance of the "expert patient" for an HIV/AIDS program in
      low income settings is critically studied to show the relevance of the developed
      countries' rhetoric of the "expert patient" approach for the reality of
      developing countries. In addition, the MoPoTsyo diabetes peer educator program is
      analyzed to show the challenges faced by the low income countries in implementing
      patient self-management programs. Finally, applications of the expert patient
      approach in China are discussed as well, to remind us of the possible
      difficulties in introducing it into rural settings.

PMID- 29063001
TI  - Trend of non-communicable disease mortality for three common conditions in the
      elderly population from 2002 to 2010: A population-based study in China.
AB  - OBJECTIVE: There is a lack of data focusing on non-communicable disease (NCD)
      mortality in the Chinese elderly population over the past decade. METHODS: Using
      mortality data from the Chinese Health Statistics, we explored the crude and age
      standardized mortality trend of three major NCDs in the Chinese population >=65
      years of age from 2002 to 2010, namely, malignant neoplasms, heart diseases, and
      cerebrovascular diseases. Subpopulations characterized as rural and urban
      residence, and by gender and age were examined separately. RESULTS: Mortality
      increased with age and was higher among males than among females across the three
      NCDs, with the gender difference being most remarkable for malignant neoplasms
      and least for heart diseases mortality. Condition-specific crude mortalities
      increased between 2002 and 2010, overall and in all the pre-specified
      subpopulations. After age-standardization, rising trends were observed for people
      >=65 years old, and condition-specific mortalities generally increased in rural
      regions and decreased in urban regions, especially for cerebrovascular diseases.
      CONCLUSIONS: There were increasing trends for mortality due to malignant
      neoplasms, heart diseases, and cerebrovascular diseases in China between 2002 and
      2010, which were largely driven by the population aging. Disparities existed by
      rural and urban residence, gender, and age.

PMID- 29063002
TI  - Clinical observation and therapeutic evaluation of intravenous pump of
      recombinant human endostatin combined with TP regimen in treating patients with
      advanced ovarian cancer.
AB  - OBJECTIVES: To observe the curative effects and adverse reactions of recombinant
      human (rh)-endostatin injection combined with a TP regimen for treating patients
      with advanced ovarian cancer. METHODS: Fifty-four patients with pathologically
      confirmed ovarian cancer were randomly divided into a combined treatment
      (intravenous pump of rh-endostatin + TP regimen) group and a control (single
      chemotherapy) group, twenty-seven patients in each group. All patients were given
      a conventional CT examination. The level of vascular endothelial growth factor
      (VEGF), the size of tumor before treatment, after 2 cycles and after 4 cycles of
      treatment were determined for the comparison of curative effects and adverse
      reactions. RESULTS: The effective rate was 37.0% (10/27) and disease control rate
      was 63.0% (17/27) in the combined treatment group after 2 cycles of treatment.
      The effective rate was 25.9% (7/27) and disease control rate was 63.0% (17/27) in
      the control group. The comparison between these two groups showed no significant
      differences (P > 0.05). The effective rate was 63.0% (17/27) and disease control
      rate was 92.6% (25/27) in the combined treatment group after 4 cycles of
      treatment. The effective rate was 29.6% (8/27) and disease control rate was 63.0%
      (17/27) in the control group. The effective rate and disease control rate between
      these two groups after 4 cycles of treatment showed significant differences (P <
      0.05). The incidences of cardiovascular toxicity, myelosuppression, sore muscles
      and joints, alopecia and gastrointestinal reaction was not significantly
      different between two groups (P > 0.05). CONCLUSION: The pump delivery of rh
      endostatin can down-regulate the expression of VEGF in ovarian cancer and has the
      better curative effect and slighter adverse reactions.

PMID- 29063003
TI  - Short- and long-term outcomes of kidney transplants with kidneys lavaged by
      retrograde perfusion technique.
AB  - OBJECTIVE: To evaluate the clinical safety and efficacy of the retrograde
      perfusion technique in kidney transplantation. METHODS: Between January 2001 and
      June 2011, 24 cases of kidney transplantation with kidneys perfused using the
      retrograde perfusion technique due to renal artery variations or injury were
      selected as the observation group (retrograde perfussion group, RP group). Twenty
      two cases of kidney transplantation via conventional perfusion were chosen as the
      control group (antegrade perfussion group, AP group). There were no statistically
      significant differences in donor data between the two groups. Cold ischemia time,
      warm ischemia time, renal perfusion time, amount of perfusion fluid, acute renal
      tubular necrosis, wound infection, urinary fistula, graft kidney function, and
      the 1-year, 3-year, and 5-year survival rates for the grafted kidney in both
      groups were observed and recorded. RESULTS: The kidney perfusion time was shorter
      in the RP group than that in the AP group (3.14 +/- 1.00 vs. 5.02 +/- 1.15 min, P
      = 0.030). There were 10 cases of acute renal tubule necrosis in the RP group and
      5 in the AP group. The length of hospital stay was 40 +/- 14 d in the RP group
      and 25 +/- 12 d in the AP group. The follow-up time was 3.5-8.5 years (mean 6.25
      years). The 1-, 3-, and 5-year survival rates for the grafted kidney were 95.8%,
      75.5%, and 65.5% in the RP group and 97.1%, 82.5%, and 68.4% in the AP group,
      respectively (P>0.05). CONCLUSIONS: This study indicates that retrograde
      perfusion is safe and practicable for cadaveric kidney harvesting and can be
      regarded as a better alternative or remedial measure for a poorly perfused kidney
      due to vascular deformity or injury.

PMID- 29063004
TI  - Lifestyle intervention for gestational diabetes mellitus prevention: A cluster
      randomized controlled study.
AB  - OBJECTIVE: The study was to examine whether gestational diabetes mellitus (GDM)
      can be prevented by early trimester lifestyle counseling in a high-risk
      population. METHODS: From September 2012 to January 2013, 1664 pregnancies in the
      Department of Obstetrics and Gynecology of First Hospital of Peking University
      were enrolled in the study during their first prenatal care visit before the 8
      gestational weeks visit and asked to fill out a questionnaire on GDM risk
      evaluation. According to the questionnaire and medical records, those with at
      least one risk factor of GDM were included in the intervention study and randomly
      allocated to two groups, intervention group and control group. Routine prenatal
      care was offered, while standardized two-step lifestyle intervention was provided
      to the intervention group during 6-8 gestational weeks, and at 12-13 gestational
      weeks, enforcement intervention based on maternal anthropometrics were offered.
      Both groups were followed until 75 g oral glucose tolerance test (OGTT) testing
      at 24-28 gestational weeks. The weight gain after intervention and the prevalence
      of GDM were used to evaluate the effect. RESULTS: (1) According to the
      International Association of Diabetes and Pregnancy Study Groups (IADPSG)
      criteria, the positive rate of GDM for the intervention group was 17.16%
      (23/134), lower than the control group which was 23.91% (33/138), P = 0.168. (2)
      The weight gain during the first and second trimester for the intervention group
      was (1.38 +/- 2.34) kg and (5.51 +/- 2.18) kg, lower than in the control group
      which was (1.41 +/- 2.58) kg and (5.66 +/- 2.25) kg, (P = 0.905, P = 0.567). (3)
      Positive rate of GDM for those fasting plasma glucose (FPG) >=5.1 mmol/L during
      early pregnancy was 11/36 (30.55%) for the intervention group that was lower than
      17/37 (45.95%) for the control group, but the statistical difference was not
      significant (P = 0.076). CONCLUSION: The positive rate of GDM could be reduced by
      a certain amount lifestyle intervention from the beginning of pregnancy. More
      validated effective intervention should be explored in the high-risk pregnant
      women.

PMID- 29063006
TI  - Multiple glomus tumor on the anteromedial side of leg.

PMID- 29063005
TI  - Keap1-Nrf2 pathway: A promising target towards lung cancer prevention and
      therapeutics.
AB  - OBJECTIVES: Drugs for targeted therapy have become a new strategy of adjuvant
      therapy for treatment of lung cancer. The Keap1 (kelch-like ECH-associated
      protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2) pathway is
      recognized to be critical in regulating genes related to the cellular protective
      response and protecting cells from oxidative damages and toxic insult. METHODS:
      Pubmed, Embase, OVID, and the Cochrane Library databases were searched from the
      beginning of each database without any limitations to the date of publication.
      Search terms were "Nrf2" or "Keap1" and "Lung cancer". RESULTS: The upregulation
      of Nrf2 had been closely related to tumor protection and drug resistance. The
      aberrant state of Keap1 or Nrf2 that were frequently found in lung cancer
      conferred a poor prognosis. Nrf2 could prevent cells from undergoing oncogenesis
      as a tumor suppressor, while it could also promote cancer progression and
      resistance to chemotherapeutic drugs as an oncogene, depending on the different
      stages of tumor progression. Target Nrf2 signaling by specific chemicals showed
      it could prevent tumor growth or combat chemoresistance. CONCLUSIONS: Increasing
      evidence has demonstrated the dual roles of the Keap1-Nrf2 pathway in tumor
      initiation and progression. In this paper, we provide a comprehensive overview of
      the potency of the Keap1-Nrf2 pathway as an antitumor target, and the current
      status of Nrf2 activators or inhibitors for therapeutic approaches. Further
      studies are required to clarify the role of Nrf2 in lung cancer at different
      tumor stages, in order to maximize the efficacy of Keap1-Nrf2 targeting agents.

PMID- 29063007
TI  - Maternal and neonatal outcomes in multiple pregnancy: A multicentre study in the
      Beijing population.
AB  - OBJECTIVE: To compare the adverse maternal and neonatal outcomes of multiple
      pregnancy and singleton pregnancy from multiple medical centers in Beijing.
      METHODS: Data concerning maternal and neonatal adverse outcomes in multiple and
      singleton pregnancies were collected from 15 hospitals in Beijing by a systemic
      cluster sampling survey conducted from 20 June to 30 November 2013. The SPSS
      software (version 20.0) was used for data analysis. The chi2 test was used for
      statistical analyses. RESULTS: The rate of caesarean deliveries was much higher
      in women with multiple pregnancies (85.8%) than that in women with singleton
      pregnancies (42.6%, chi2 = 190.8, P < 0.001). The incidences of anemia (chi2 =
      40.023, P < 0.001), preterm labor (chi2 = 1021.172, P < 0.001), gestational
      diabetes mellitus (chi2 = 9.311, P < 0.01), hypertensive disorders (chi2 =
      122.708, P < 0.001) and post-partum hemorrhage (chi2 = 48.550, P < 0.001) was
      significantly increased with multiple pregnancy. In addition, multiple pregnancy
      was associated with a significantly higher rate of small-for-gestational-age
      infants (chi2 = 92.602, P < 0.001), low birth weight (chi2 = 1141.713, P <
      0.001), and neonatal intensive care unit (NICU) admission (chi2 = 340.129, P <
      0.001). CONCLUSIONS: Multiple pregnancy is a significant risk factor for adverse
      maternal and neonatal outcomes in Beijing. Improving obstetric care for multiple
      pregnancy, particularly in reducing preterm labor, is required to reduce the risk
      to mothers and infants.

PMID- 29063008
TI  - Does novel oral anticoagulant improve anticoagulation for non-valvular atrial
      fibrillation associated stroke: An inpatient registration study in Shanghai.
AB  - OBJECTIVE: To summarize the use rate, safety, efficacy of antithrombotics in
      stroke/transient ischemic attack (TIA) prevention, and reasons for not using
      dabigatran etexilate (DE) in Shanghai, China. METHODS: Non-valvular atrial
      fibrillation (NVAF)-associated stroke patients were prospectively registered as
      an electronic database. Use rate of antithrombotics and reasons for not using DE
      were extracted during follow-up. Patients' baseline characteristics, recurrent
      ischemic stroke/TIA events and bleeding complications were analyzed. PATIENTS:
      From April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were
      studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h
      Holter and echocardiography. RESULTS: Before introduction of DE (April 2013), use
      rates of warfarin and antiplatelets were 28.9% (11/38) and 60.5% (23/38)
      respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8%
      (15/72), 12.5% (9/72), and 43.1% (31/72). The DE did not improve use of
      anticoagulants (P = 0.639). There were 19 (17.3%) recurrent ischemic stroke
      events up to October 2015; two (9.5%) in the non-user group, 10 (18.5%) in the
      antiplatelet group, and seven (20.0%) in the anticoagulants group (P = 0.570).
      Furthermore, recurrence rates were similar between the DE group (20.0%) and the
      Warfarin group (20.0%, P = 1.000). The most common reason for not using DE was
      financial concerns (61.0%), followed by inconvenience to purchase (14.0%) and
      hemorrhage concerns (11.0%). Two patients using warfarin found fecal occult blood
      so they stopped warfarin and began to use antiplatelet drugs. No bleeding event
      occurred in the other groups. Only one patient had side effects (dyspepsia and
      gastroesophageal reflux) from DE. CONCLUSION: The use rate of either DE or
      warfarin in Shanghai was low; DE had not improved anticoagulation therapy for
      NVAF patients in Shanghai mainly because DE had not been covered by health
      insurance.

PMID- 29063009
TI  - Identifying at-risk foot among hospitalized patients with type 2 diabetes: A
      cross-sectional study in one Chinese tertiary hospital.
AB  - OBJECTIVE: To investigate the prevalence of diabetic at-risk foot and its
      associated factors. METHODS: A total of 838 hospitalized patients with type 2
      diabetes were screened for at-risk foot. Neural and vascular disorders were
      evaluated by assessing vibration perception thresholds and ankle brachial indexes
      (ABIs). After excluding 12 patients with abnormally high ABIs, remaining
      individuals with neural and/or vascular disorder were identified as at-risk
      patients and further classified into three subtypes: isolated neural disorder,
      isolated vascular disorder and mixed disorder. Potential associated factors were
      examined using Logistic regression models. RESULTS: In the final sample of 826
      individuals, the prevalence of diabetic at-risk foot was 30.6%. Among all at-risk
      patients, isolated neural disorders (69.6%) were more common than mixed (16.2%)
      or isolated vascular disorders (14.2%). Isolated neural and vascular disorders
      shared specific risk factors, including age per 20-year increment (odds ratio
      [95% CI], 3.73 [2.59-5.37] and 4.01 [1.98-8.11]), diabetic duration >=10 years
      (1.69 [1.13-2.54] and 3.29 [1.49-7.24]) and systolic blood pressure >=140 mmHg
      (1.96 [1.31-2.93] and 2.90 [1.38-6.10]) respectively. In addition, isolated
      neural disorders were associated with a heavy smoking history (95%CI 2.69 [1.15
      6.31]), increased high-sensitivity C-reactive protein levels (95%CI 1.30 [1.04
      1.62]) and mild obesity (95%CI 0.49 [0.20-1.24]). Isolated vascular disorders
      were linked with decreased high density lipoprotein (HDL) cholesterol levels
      (95%CI 3.42 [1.31-8.96]) and increased triglycerides levels (95%CI 2.74 [1.26
      5.97]). CONCLUSIONS: Diabetic at-risk foot is epidemic among hospitalized
      patients with type 2 diabetes. Aging, long-term diabetes, hypertension, smoking,
      inflammatory response and dyslipidemia may be associated with the prevalence of
      diabetic at-risk foot.

PMID- 29063010
TI  - Clinical analysis of retroperitoneoscopic nephroureterectomy for renal
      tuberculosis.
AB  - OBJECTIVES: To explore the feasibility and safety of retroperitoneoscopic
      nephroureterectomy for kidney tuberculosis. METHODS: Forty-eight
      retroperitoneoscopic nephroureterectomies and thirty-five nephroureterectomies
      for kidney tuberculosis procedures were performed from June 2008 to December
      2014. The patients consisted of 53 males and 30 females with a mean age of 36
      years (range: 26-51 years). The patients' data were reviewed and analyzed.
      RESULTS: The retroperitoneoscopic nephroureterectomy procedures were completed
      successfully in 48 cases with no conversions to open surgery. The mean operating
      time was 170 minutes (range: 121-258 minutes), the mean blood loss was 110 ml
      (range: 70-250 ml), and the mean hospital stay was 5.70 days (range: 5-14 days);
      these were all much less than nephroureterectomy procedures (P < 0.05). A total
      of five minor complications (10.4%) occurred, injury to the peritoneum was
      observed in three patients, and infection at the incision site was observed in
      two patients, there were no obvious difference between the two surgical methods
      (P > 0.05). Seventy-five patients were followed up, and the average follow-up
      time was 12.5 months (range: 6-20 months). All the patients recovered without any
      lesions remaining. CONCLUSIONS: The results of this study indicate that
      retroperitoneoscopic nephroureterectomy is a feasible, safe, effective, and less
      invasive treatment modality for treating renal tuberculosis.

PMID- 29063011
TI  - Polymer-free versus permanent polymer drug eluting stents in coronary artery
      disease: A meta-analysis of 10 RCTs with 6575 patients.
AB  - BACKGROUND: Permanent polymer drug eluting stents (PP-DES) may induce
      inflammation of the vessel wall due to the existence of the polymer, which may
      delay intimal healing. Polymer-free DES (PF-DES) that eliminate the polymeric
      carrier may potentially lead to safer DES. However, the safety and efficacy of PF
      DES remains controversial. METHODS: Randomized controlled trials comparing PF-DES
      with PP-DES were searched in online database including MEDLINE, Excerpta Medica
      Database (EMBASE) and Cochrane Library. Studies reporting late lumen loss (LLL),
      all-cause death, myocardial infarction (MI), target lesion revascularization
      (TLR) and late stent thrombosis (LST) were enrolled and quantitatively analyzed.
      RESULTS: Ten studies enrolling 6575 patients were included in this meta-analysis.
      The PF-DES showed a benefit in reducing all-cause death (OR = 0.77, 95% CI: 0.61
      to 0.98, P = 0.03) and long-term LLL (weighted mean difference (WMD) -0.16 mm,
      95% CI: -0.22 to -0.11 mm, P < 0.001), while no superiority was found in reducing
      short-term LLL (WMD 0.03 mm, 95% CI: -0.07-0.13 mm, P = 0.57), MI (OR = 1.12, 95%
      CI: 0.19 to 23.18, P = 0.39), TLR (OR = 1.19, 95% CI: 0.42 to 3.38, P = 0.83) and
      LST (OR = 0.92, 95% CI: 0.05 to 5.71, P = 0.74). CONCLUSION: PF-DES showed
      benefits in reducing long-term LLL and mortality compared with PP-DES, but no
      superiority was found in short-term LLL, MI, TLR and LST. These findings provide
      a sound basis for the wide application of PF-DES in the future.

PMID- 29063012
TI  - Study progress of berberine for treating cardiovascular disease.
AB  - Berberine (BBR) is a natural alkaloid isolated from the Coptis chinensis. While
      this plant has been used in Chinese medicine for more than 2500 years, interest
      in its effects in treating cardiovascular disease has been growing in the last
      decade. Recent researches showed that BBR had the effect of anti-heart failure,
      anti-hypertension, anti-hyperlipidemia, anti-insulin resistance, anti
      arrhythmias, and anti-platelet aggregation.

PMID- 29063013
TI  - A meta-analysis of the prognosis in patients with breast cancer with ipsilateral
      supraclavicular lymph node metastasis versus patients with stage IIIb/c or IV
      breast cancer.
AB  - OBJECTIVE: To systematically evaluate the prognosis in patients with breast
      cancer with ipsilateral supraclavicular lymph node metastasis (SLNM) versus
      patients with stage IIIb/c or IV breast cancer, so as to provide evidence for
      clinical practice and research. METHODS: Computer retrieval from PubMed, Cochrane
      Libratory, CNKI (China National Knowledge Infrastructure), CBM and Wanfang
      Database with the assistance of other retrieval tools. All the studies evaluating
      the prognosis in patients with breast cancer with ipsilateral supraclavicular
      lymph node metastasis versus patients with stage IIIb/c or IV breast cancer were
      collected. Quality assessment was performed for the included data based on the
      quality assessment criteria appropriate for this study. Meta-analysis was
      performed using RevMan 5.3 software. RESULTS: A total of four references (1277
      patients) were included. Assessment of influences on prognosis: As compared to
      the stage IIIb/c group, the 5-year survival rate was slightly lower in the SLNM
      group (relative risk (RR) 0.79; 95% confidence interval (CI) 0.59-1.06; Z = 1.55,
      P = 0.12), but there was no statistical significance; in contrast, the 5-year
      survival rate was significantly increased in the SLNM group as compared to the
      stage IV group (RR = 2.70; 95%CI: 1.36-5.37; Z = 2.84, P = 0.005). As compared to
      the stage IIIb/c group, the 5-year disease-free survival rate was lower in the
      SLNM group (RR = 0.65; 95%CI: 0.40-1.05; Z = 1.75, P = 0.08); however, there was
      no statistical significance. CONCLUSIONS: In patients with advanced breast cancer
      receiving combined therapy, the prognosis in patients with breast cancer with
      ipsilateral SLNM was significantly better than in those with stage IV breast
      cancer, and slightly worse than those with stage IIIb/c breast cancer. However,
      with the scarcity and poor quality of these observational studies, the long-term
      prognosis remains to be further verified in large-sample, high-quality studies.

PMID- 29063014
TI  - The value of the speech audiometry in diagnosis of X-linked adrenoleukodystrophy.

PMID- 29063016
TI  - Mass prevention and treatment: Fundamental strategy for chronic disease control
      and prevention.

PMID- 29063015
TI  - Esophageal ulcer induced by ibuprofen tablets.

PMID- 29063017
TI  - Clinical considerations of lipid target and goal in dyslipidemia control.

PMID- 29063018
TI  - Amendment of the low-density lipoprotein cholesterol target in the 'Chinese
      Guidelines for the Prevention and Treatment of Adult Dyslipidemia': Opinion.

PMID- 29063019
TI  - Advances for achieving a pathological complete response for rectal cancer after
      neoadjuvant therapy.
AB  - Neoadjuvant therapy has become the standard of care for locally advanced mid-low
      rectal cancer. Pathological complete response (pCR) can be achieved in 12%-38% of
      patients. Patients with pCR have the most favorable long-term outcomes.
      Intensifying neoadjuvant therapy and extending the interval between termination
      of neoadjuvant treatment and surgery may increase the pCR rate. Growing evidence
      has raised the issue of whether local excision or observation rather than radical
      surgery is an alternative for patients who achieve a clinical complete response
      after neoadjuvant therapy. Herein, we highlight many of the advances and
      resultant controversies that are likely to dominate the research agenda for pCR
      of rectal cancer in the modern era.

PMID- 29063020
TI  - Granulomatous lobular mastitis.
AB  - Granulomatous lobular mastitis is an unusual breast benign inflammatory disorder
      with unknown aetiology. It is generally emerged with the clinical symptoms of
      breast mass, abscess, inflammation and mammary duct fistula. The diagnosis is
      made by histopathology with a chronic non-necrotizing granulomatous inflammation
      in lobules of the breast tissue as the microscopic feature. Therapy of
      granulomatous lobular mastitis consists of surgical, medication treatment or
      combination of both, but now researches suggest that observational management is
      an acceptable treatment.

PMID- 29063021
TI  - Changes of junctions of endothelial cells in coronary sclerosis: A review.
AB  - Atherosclerosis, the major cause of cardiovascular diseases, has been a leading
      contributor to morbidity and mortality in the United States and it has been on
      the rise globally. Endothelial cell-cell junctions are critical for vascular
      integrity and maintenance of vascular function. Endothelial cell junctions
      dysfunction is the onset step of future coronary events and coronary artery
      disease.

PMID- 29063022
TI  - High uric acid level predicts left atrial thrombus or spontaneous echo contrast
      detected by transesophageal echocardiography: Meta-analysis and systematic
      review.
AB  - BACKGROUND: Recent observational studies have suggested that the patients with
      hyperuricemia have a higher risk of having left atrial thrombus (LATH) or left
      atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography
      (TEE), while the ultimate predictive value of a high uric acid (UA) level on
      LATH/LASEC remained obscure. METHODS: We searched the PubMed and Cochrane
      clinical trials databases up to July 2015. Following screening the 369 initially
      identified studies, we analyzed six observational studies with 2381 patients.
      RESULTS: The meta-analysis of these studies showed that an elevated serum UA
      level was associated with a higher likelihood of LATH/LASEC (OR = 1.59, 95%CI
      1.13-2.23, P = 0.008), while significant differences exist among individual
      trials (P < 0.00001 and I2 = 85%). Sensitivity analysis failed to find any
      heterogeneity. CONCLUSION: An elevated UA level was associated with a higher risk
      of detecting a left atrial abnormality represented by LATH/LASEC.

PMID- 29063023
TI  - Comparison of maintenance effect of probiotics and aminosalicylates on ulcerative
      colitis: A meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the maintenance effect of probiotics versus that of
      aminosalicylates on ulcerative colitis. METHODS: MEDLINE, EMBASE, the Cochrane
      Controlled Trials Register, and the Chinese Biomedical Database were searched in
      English or Chinese. Data extracted were selected with strict criteria. RESULTS:
      In six randomized controlled trials (RCTs), a total of 721 participants were
      enrolled and the maintenance effect of probiotics (n = 364) versus that of
      aminosalicylates (n = 357) on ulcerative colitis was investigated. No significant
      difference was observed between probiotics and aminosalicylate groups (relative
      risk (RR) = 1.08; 95% confidence interval (CI): 0.91-1.28; P = 0.40). Three RCTs
      compared the incidence of adverse events with probiotics versus those with
      aminosalicylates. No significant difference was observed in the incidence of
      adverse events between the two groups (RR = 1.20; 95% CI: 0.92-1.56; P = 0.17).
      CONCLUSIONS: Probiotics and aminosalicylates both showed a maintenance effect on
      ulcerative colitis. However, more well-designed RCTs are required.

PMID- 29063024
TI  - The value of three-dimensional helical computed tomography for the retrograde
      flexible ureteronephroscopy in the treatment of lower pole calyx stones.
AB  - OBJECTIVE: The aim of our study was to determine if there is any advantage of
      three-dimensional helical computed tomography (3D-HCT) over intravenous urogram
      (IVU) for the retrograde flexible ureteronephroscopy in the treatment of lower
      pole calyx stones. METHODS: From June 2012 to January 2014, a total of 52 cases
      of lower pole renal stones underwent retrograde intrarenal surgery (RIRS) in our
      center. All patients underwent a preoperative IVU and three-dimensional helical
      computed tomography urography (3D-CTU) program to define the collecting system
      anatomy, manly concerning the following lower pole features; infundibu-lopelvic
      angle (IPA), infundibular length (IL), and infundibular width (IW). The
      examinations were performed in the same center of reference with a standardized
      method and with 3D-HCT Siemens Somaton Plus equipment. The measurements were
      performed by the same researcher, using a ruler and a square. RESULTS: Based on
      clinical threshold difference of the anatomic factors on an IVU image to compare
      the difference between an IVU image and a 3D-CT image of 52 patients, the IPA was
      <30 degrees  when measured on intravenous pyelography (IVP) for 21 patients. We
      found that with the IPA of <30 degrees  measured with IVP only 19% (4/21) were
      correctly classified in the same size category using 3D-HCT, whereas 81% (17/21)
      were upgraded to 40-50 degrees  on 3D-CT. This difference was significant between
      IVP and 3D-HCT. CONCLUSIONS: 3D-HCT has advantages over IVU when analyzing the
      morphometric and the morphological features of kidney lower pole spatial anatomy
      for the retrograde flexible ureteronephroscopy in the treatment of lower pole
      calyx stones.

PMID- 29063025
TI  - Relationships between serum Omentin-1 levels and bone mineral density in older
      men with osteoporosis.
AB  - OBJECTIVE: To investigate the correlation between serum Omentin-1 levels and the
      presence of osteoporosis in older men. METHODS: Serum Omentin-1, bone turnover
      biochemical markers, and bone mineral density (BMD) were determined in 45 older
      men with osteoporosis or 45 older men without osteoporosis (65-70 years old).
      RESULTS: Omentin-1 levels were increased in older men with osteoporosis, and the
      differences remained significant after controlling for fat mass. Omentin-1 was
      negatively correlated with BMD. In a multiple linear stepwise regression
      analysis, Omentin-1, lean mass, but not fat mass, were independent predictors of
      BMD for the combined group. Significant negative correlations between Omentin-1
      and bone-specific alkaline phosphatase (BAP) and bone cross-linked N-telopeptides
      of type I collagen (NTX) were found. Omentin-1 was also independently associated
      with BMD and bone turnover markers in older men with osteoporosis and control
      groups that were considered separately. CONCLUSIONS: Omentin-1 is an independent
      predictor of BMD in older men with osteoporosis, and it is negatively correlated
      with bone turnover biochemical markers. It is suggested that Omentin-1 may exert
      a negative effect on bone mass through the regulation of the osteoblast
      differentiation in the older men with osteoporosis.

PMID- 29063026
TI  - Relationship between occult hepatitis B virus infection and chronic kidney
      disease in a Chinese population-based cohort.
AB  - OBJECTIVE: Previous studies have revealed inconsistent results regarding the
      association between occult hepatitis B virus (HBV) infection and chronic kidney
      disease (CKD). Therefore, we conducted a prospective cohort study to evaluate the
      association between occult HBV infection and CKD. METHODS: A total of 4329
      adults, aged 46.2 +/- 13.7 years, without CKD at baseline were enrolled while
      undergoing physical examinations. Occult HBV infection was defined as
      seropositivity for antibody to HBV core antigen. CKD was defined as decreased
      estimated glomerular filtration rate (eGFR < 60 ml.min-1.1.73 m-2) or presence of
      proteinuria >=1+, assessed using a repeated dipstick method. eGFR was computed
      using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
      RESULTS: The prevalence of occult HBV infection was 8.1% (352/4329). During 5
      years of follow-up, 165 patients (3.8%) developed CKD. Univariate Logistic
      regression analysis showed that occult HBV infection was positively associated
      with decreased eGFR, with an odds ratio (OR) of 2.15 (95% confidence interval
      (CI): 1.05-4.11). In contrast, occult HBV infection was not associated with
      either proteinuria or CKD (P > 0.05). After adjustment for potential confounders
      in the multivariate Logistic regression analysis, age, hypertension, diabetes,
      and the highest quartile of uric acid were associated with CKD, with ORs of 1.04
      (95% CI: 1.02-1.05), 2.1 (95% CI: 1.46-3.01), 2.02 (95% CI: 1.36-2.99), and 1.86
      (95% CI: 1.17-2.95), respectively. However, occult HBV infection was not
      associated with CKD, with an OR of 1.12 (95% CI: 0.65-1.95). CONCLUSIONS: This
      study did not find an association between occult HBV infection and CKD. However,
      high-risk patients infected with HBV should still be targeted for monitoring for
      the development of CKD.

PMID- 29063028
TI  - Elevation of serum uric acid and incidence of type 2 diabetes: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: Recently, several cohort studies suggested a positive relationship
      between serum uric acid (SUA) and type 2 diabetes mellitus (T2DM), which is
      inconsistent with the results of functional research. Our aim was to further
      evaluate this correlation by conducting a systematic review. METHODS:
      Computerized literature searches of the Medline database, EMBASE database, and
      PubMed were used to evaluate the relationship between SUA and T2DM in cohort
      studies. Cochran's Q and I2 statistics were used to evaluate heterogeneity among
      studies, and pooled relative risk (RR) and odds ratio (OR) with 95% confidence
      intervals (CIs) were calculated using random-effects and fixed-effects models.
      The summary RR and OR of per 1 mg/ml-SUA increase were calculated separately
      because of their different epidemiological implications and calculation methods.
      Additionally, sensitivity analysis, stratified analysis, meta-regression, and
      multiple meta-regression were applied to investigate the heterogeneity among
      studies. RESULTS: A total of 970 articles were retrieved from the searches.
      Sixteen publications of cohort studies containing 61,714 participants were
      included. The pooled RR was 1.131 (95% CI: 1.084-1.179) with significant
      heterogeneity among studies (I2  = 51.9%, P = 0.018). Adjusted RR to evaluate the
      stability of the relationship between SUA and T2DM in the sensitivity analysis
      was similar (RR = 1.140, 95% CI: 1.087-1.197), with statistically significant
      heterogeneity (I2  = 54.5%, P = 0.015). Stratified analysis and meta-regression
      showed that the positive relationship remained irrespective of age, sex, region,
      and adjustment for confounding factors including body mass index, fasting blood
      glucose, systolic blood pressure, diastolic blood pressure, alcohol consumption,
      smoking, blood cholesterol, waist circumference, fatty liver, and drugs affecting
      SUA. CONCLUSION: Although SUA is independently associated with development of
      T2DM, insulin resistance increased as the baseline SUA concentration increased;
      thus, the correlation between SUA and T2DM requires further evaluation and the
      baseline insulin resistance status should also be considered.

PMID- 29063027
TI  - Regulatory T-cells promote hepatitis B virus infection and hepatocellular
      carcinoma progression.
AB  - Regulatory T-cells (Tregs), known for their immune suppressive function, have
      been reported in higher numbers, with activated phenotypes and greater potency,
      in hepatitis B virus (HBV)-related liver diseases than in normal conditions. The
      numbers, phenotypes, and function of intrahepatic and/or tumor-infiltrating Tregs
      in HBV-related liver diseases also differ from those of Tregs in the peripheral
      blood. By inhibiting the function of effector T-cells (Teffs), Tregs play a
      substantial role in the formation and maintenance of the liver's suppressive
      microenvironment, which might account for the progression of HBV-related
      hepatitis and hepatocellular carcinoma (HCC). In acute hepatitis B virus
      infection, Tregs can safeguard the liver from damage at the cost of prolonged
      antiviral processes, which results in chronic HBV infection in the liver.
      Furthermore, Tregs play a role in the development of cirrhosis, the
      transformation of cirrhosis to HCC, and the progression and metastasis of HCC.
      Higher levels of Tregs in the peripheral blood and/or tumor sites signify a
      poorer prognosis in HBV-related liver conditions, and observational data from
      mouse models and human patients support the theory that depleting Tregs may be
      therapeutic in HBV-related liver diseases by inducing antiviral and antitumor
      immunity.

PMID- 29063029
TI  - Stem cell transplantation dose in patients with acute myocardial infarction: A
      meta-analysis.
AB  - OBJECTIVE: To evaluate whether stem cell transplantation improves global left
      ventricular ejection fraction (LVEF) in patients with acute myocardial infarction
      (AMI), and to determine the appropriate stem cell therapy dose as well as the
      effective period after stem cell transplantation for therapy. METHODS: A
      systematic literature search included Pubmed, MEDLINE, China National Knowledge
      Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Cochrane
      Evidence-Based Medicine databases. The retrieval time limit ranged from January
      1990 to June 2016. We also obtained full texts through manual retrieval,
      interlibrary loan and document delivery service, or by contacting the authors
      directly. According to our inclusion and exclusion criteria, data were extracted
      independently by two evaluators. In case of disagreement, a joint discussion
      occurred and a third researcher was utilized. Data were analyzed quantitatively
      using Revman 5.2. Summary results are presented as the weighted mean difference
      (WMD) with 95% confidence intervals (CIs). We collected individual trial data and
      conducted a meta-analysis to compare changes in global left ventricular ejection
      fraction (DeltaLVEF) after stem cell therapy. In this study, four subgroups were
      based on stem cell dose (<=1 * 107 cells, <=1 * 108 cells, <=1 * 109 cells, and
      <=1 * 1010 cells) and three subgroups were based on follow-up time (<6 months, 6
      12 months, and >=12 months). RESULTS: Thirty-four studies, which included 40
      randomized controlled trials, were included in this meta-analysis, and 1927
      patients were evaluated. Changes in global LVEF were significantly higher in the
      stem cell transplantation group than in the control group (95% CI: 2.35-4.26%, P
      < 0.01). We found no significant differences in DeltaLVEF between the bone marrow
      stem cells (BMCs) group and control group when the dose of BMCs was <=1 * 107
      [DeltaLVEF 95% CI: 0.12-3.96%, P = 0.04]. The DeltaLVEF in the BMCs groups was
      significantly higher than in the control groups when the dose of BMCs was <=1 *
      108 [DeltaLVEF 95% CI: 0.95-4.25%, P = 0.002] and <=1 * 109 [DeltaLVEF 95% CI:
      2.31-4.20%, P < 0.01]. In addition, when the dose of BMCs was between 109 and
      1010 cells, we did not observe any significant differences [DeltaLVEF 95% CI: 
      0.99-11.82%, P = 0.10]. Our data suggest stem cell therapy improves cardiac
      function in AMI patients when treated with an appropriate dose of BMCs.
      CONCLUSION: Stem cell transplantation after AMI could improve global LVEF. Stem
      cells may be effectively administered to patients with AMI doses between 108 and
      109 cells.

PMID- 29063031
TI  - Association between quality of life and anxiety, depression, physical activity
      and physical performance in maintenance hemodialysis patients.
AB  - OBJECTIVE: Maintenance hemodialysis (MHD) patients often have impaired quality of
      life (QOL), anxiety, depression, and reduced daily physical activity (DPA) and
      physical performance. The contributions of these latter factors to reduced QOL in
      MHD are poorly understood. We examined the association of QOL with anxiety,
      depression, DPA, and physical performance. METHODS: Seventy-two relatively
      healthy adult MHD patients, vintage >=6 months, and 39 normals of similar age
      range and gender distribution were studied. QOL was assessed using the Kidney
      Disease Quality of Life-Short Form (KDQOL-SF). Anxiety and depression were each
      evaluated with two questionnaires. DPA and physical performance were assessed
      with a physical activity monitor, Human Activity Profile, and 6-minute walk, sit
      to-stand, and stair-climbing tests. RESULTS: Most KDQOL components were reduced
      in MHD patients versus normals. KDQOL components in patients were commonly
      inversely correlated with measures of anxiety and depression (P < 0.05) and were
      more reduced in patients with both anxiety and depression. KDQOL was often
      impaired in patients with either anxiety or depression. However, most KDQOL
      scores did not differ between patients and normals without anxiety or depression.
      DPA, Human Activity Profile, and physical performance often correlated with KDQOL
      scores in adjusted models, but after further adjustment for anxiety and
      depression, DPA, Human Activity Profile, and physical performance correlated less
      frequently with KDQOL scores. This reduction in significant correlations after
      adjustment for anxiety and depression was particularly pronounced for the
      association between KDQOL and DPA. CONCLUSION: In relatively healthy MHD
      patients, KDQOL scores are usually decreased in those with anxiety and/or
      depression but are usually normal in those without anxiety or depression. Lower
      DPA in MHD patients with reduced KDQOL scores often appears to be associated with
      anxiety and depression. The relationship between QOL and physical performance
      appears to be less influenced by anxiety and/or depression. These data suggest
      that treatment of anxiety and depression in MHD patients may improve their QOL,
      DPA, and possibly physical performance.

PMID- 29063030
TI  - Risk stratification of atherosclerotic cardiovascular disease in Chinese adults.
AB  - OBJECTIVE: This study aims to determine the distribution of observed
      atherosclerotic cardiovascular disease (ASCVD) incidence in contemporary cohorts
      in China, and to identify cut-off points for ASCVD risk classification based on
      traditional criteria and new equations developed by Prediction for ASCVD Risk in
      China (China-PAR). METHODS: The study populations included cohorts in the China
      PAR project, with 34,757 participants eligible for the current analysis.
      Traditional risk stratification was assessed by using Chinese guidelines on
      prevention of CVD and hypertension, and 5 risk groups were classified based on
      these guidelines after slight modification for available risk factors. Kaplan
      Meier analysis was conducted to obtain the cumulative incidence of observed ASCVD
      events for all subjects and sub-groups. The predicted 10-year ASCVD risk was
      obtained using the China-PAR equations. RESULTS: A total of 1922 ASCVD events
      were identified during an average follow-up of 14.1 years. According to the group
      classification based on traditional risk stratification, the observed 10-year
      risks for ASCVD were 4.61% (95% confidence interval [CI]: 4.11-5.10%) in the
      moderate-risk group and 8.74% (95% CI: 7.82-9.66%) in the high-risk group. Based
      on the China-PAR equations for risk assessment of ASCVD, those with predicted
      risks of <5%, 5-10%, and >=10% could be classified into categories of low-,
      moderate-, and high-risk for ASCVD, respectively. CONCLUSION: The findings enable
      development of a simple method for classification of individuals into low-,
      moderate-, and high-risk groups, based on the China-PAR equations. The method
      will be useful for self-management and prevention of ASCVD in Chinese adults.

PMID- 29063033
TI  - Study of the features of coronary artery atheromatous plaque using intravascular
      ultrasound in patients with impaired glucose tolerance.
AB  - OBJECTIVE: We used intravascular ultrasound (IVUS) to analyze the features of
      coronary artery atheromatous plaque in patients with impaired glucose tolerance
      and mild-to-moderate angiographic coronary stenosis. The aim was to determine the
      clinical significance of plaque characteristics as well as the relationship
      between hemoglobin A1c (HbA1c) levels and coronary artery lesions. METHODS: HbA1c
      levels were evaluated in 85 patients (96 lesions), of whom 46 had impaired
      glucose tolerance (IGT Group) and 39 had normal blood glucose (NBG Group). IVUS
      was used to analyze the lesion vessel of both groups qualitatively and
      quantitatively. The external elastic membrane area (EEMA), minimal lumen area
      (MLA), plaque area (PA), and plaque burden (PB) were measured for both the target
      lesion and the reference segments (reference external elastic membrane area
      (REEMA), reference minimal lumen area (RMLA), reference plaque area (RPA), and
      reference plaque burden (RPB), respectively). RESULTS: HbA1c levels were
      significantly higher in the IGT Group than in the NBG Group (P < 0.05). In the
      IGT Group there was more soft plaque, eccentric plaque, and positive remodeling,
      and less calcification, while in the NBG Group there was much harder plaque and
      calcification, no reconstruction, and negative remodeling (P < 0.05). MLA was
      smaller in the IGT Group than in the NBG Group, while EEMA, PA, and PB were
      clearly greater (P < 0.05). In the meantime, RMLA was clearly smaller in the IGT
      Group than in the NBG Group, while RPA and RPB were greater (P < 0.05). HbA1c
      levels were positively correlated with PA and PB, and negatively correlated with
      MLA. CONCLUSION: IVUS is very valuable for the evaluation of mild-to-moderate
      coronary lesions. The coronary artery lesions in patients with IGT are more
      serious and widespread than those in patients with NBG. HbA1c levels might be of
      some value in assessing the severity of coronary artery lesions.

PMID- 29063032
TI  - Prevalence of active and passive tobacco smoking among Beijing residents in 2011.
AB  - OBJECTIVES: This study was aimed to investigate the prevalence of active and
      passive tobacco smoking among Beijing residents in 2011. METHODS: A cross
      sectional survey was conducted, using a stratified multistage cluster random
      sampling method to select a representative sample of 20,242, among Beijing
      residents aged 18-79 years. Active and passive tobacco smoking information was
      collected by a standardized and validated questionnaire in a face-to-face
      interview. All estimates of prevalence and numbers were weighted by the 2010
      Beijing Population Census data and the sampling scheme. RESULTS: Among Beijing
      residents aged 18-79 years, the overall prevalence of ever smokers and current
      smokers were 33.13% and 30.18%, respectively. The prevalence in males was much
      higher than that in females (60.75% vs. 3.75% for ever smokers, and 55.53% vs.
      3.21% for current smokers, respectively). For overall current smokers, 14.12
      cigarettes were consumed per day. However, only 8.91% of ever smokers quitted
      smoking at the time of the survey, and 2.44% of ever smokers quitted smoking in
      recent two years. Furthermore, 44.74% of overall nonsmokers and former smokers,
      with 47.03% of males and 43.63% of females, reported exposure to secondhand smoke
      for at least 15 minutes per day and at least one day per week. CONCLUSIONS:
      Tobacco smoking prevalence is still extremely high in Beijing. Nonsmokers do
      still suffer from secondhand smoke critically. Further urgent efforts for tobacco
      control are warranted in Beijing.

PMID- 29063034
TI  - Advances in endovascular therapy for ischemic cerebrovascular diseases.
AB  - Endovascular therapy for ischemic cerebrovascular diseases has developed rapidly
      in recent years. The latest clinical trials of acute ischemic stroke have shown
      promising results with the continued advancement of concepts, techniques, and
      materials. Mechanical thrombectomy is recommended in the treatment of acute
      ischemic stroke caused by large vessel occlusion of the anterior circulation,
      according to the guidelines updated in Europe, USA, and China. The long-term
      therapeutic efficacy of endovascular stenting for carotid artery stenosis has
      also been proved noninferior to that of carotid endarterectomy. However, the
      latest clinical trials have shown that the efficacy of stenting for intracranial
      artery and vertebral artery stenosis is inferior to that of medical treatment
      alone, which needs urgent attention through further development and studies.

PMID- 29063035
TI  - Endoscopic treatment of hypertensive intracerebral hemorrhage: A technical
      review.
AB  - Hypertensive intracerebral hemorrhage (ICH) is still a highlighting global issue.
      Endoscopic evacuation as a minimally invasive treatment became an alternative
      other than conventional craniotomy and catheter drainage for ICH. However, there
      is no unified indication or standardized procedure on endoscopic treatment of
      ICH. Here we explored the literature and gathered information from different
      studies, to review the background, technical points, and existing problems of
      endoscopic treatment for ICH.

PMID- 29063036
TI  - Diabetes awareness, treatment, control rates and associated risk factors among
      Beijing residents in 2011: A cross-sectional survey.
AB  - OBJECTIVE: To examine the awareness, treatment and control rates of diabetes and
      identify their associated risk factors among Beijing residents. METHODS: A cross
      sectional survey was conducted in 2011, using a stratified multistage cluster
      random sampling method to select a representative sample of 20,242 residents in
      Beijing aged 18-79 years. Diabetes was defined as fasting blood glucose (FBG)
      >=7.0 mmol/L and/or history of diabetes and/or using insulin or hypoglycemic
      agents. All estimates of awareness, treatment and control rates were weighted by
      the 2010 Beijing Population Census data and the sampling scheme. Multivariate
      Logistic regression was used to identify factors associated with awareness,
      treatment and control rates. RESULTS: A total of 2061 (10.3%) participants were
      diagnosed as diabetes. The overall awareness, treatment and control rate among
      patients were 60.9%, 51.3% and 22.4%, respectively, while overall control rate
      among treated patients was 33.8%. These rates differed across subgroups. Women
      were more likely to be aware of diabetes status, receive treatment and have
      better glucose controlled than men (69.5% vs. 54.7% for awareness, 61.0% vs.
      44.3% for treatment, and 27.6% vs. 18.6% for control, respectively). In addition,
      only 22.2% of treated patients had both FBG and hemoglobin A1c (HbA1c) controlled
      well. Multivariate Logistic regression suggested that old age, women, higher
      education and family history of diabetes were associated with higher awareness,
      treatment and control rates (All P < 0.05). Treated individuals living in rural
      (OR = 0.67(95%CI: 0.47-0.96)) or with dyslipidemia (OR = 0.63 (95%CI: 0.44-0.91))
      had a lower diabetic control rate. CONCLUSIONS: Awareness, treatment and control
      rates of diabetes in Beijing were still low. A comprehensive intervention
      strategy on diabetes management and control is warranted.

PMID- 29063037
TI  - Coronary artery plaque imaging: Comparison of black-blood MRI and 64
      multidetector computed tomography.
AB  - OBJECTIVE: To comparatively evaluate black-blood coronary arterial wall MRI and
      64-multidetector computed tomography (64-MDCT) for detection and classification
      of coronary artery plaques. METHODS: We included 15 patients with confirmed
      coronary artery plaques in the proximal or middle segments of coronary arteries
      by 64-MDCT, who underwent black-blood coronary wall MRI at 1.5 T within 10 days.
      Cross-sectional coronary wall images were acquired using a 2D double-inversion
      recovery, electrocardiograph-triggered, navigator-gated, fat-suppressed, turbo
      spin-echo sequence on the coronary arteries with lesions from the ostium to the
      middle segment continuously without gap. The vessel cross-sectional area (CSA),
      luminal CSA, maximal wall thickness, plaque burden, contrast-to-noise ratio
      (CNR), and signal-to-noise ratio (SNR) were measured in each slice and
      subsequently compared with computed tomography angiography (CTA) images. CTA
      images were divided into 5-mm segments for side-by-side comparison with MRI.
      RESULTS: Of the 15 patients, 12 were enrolled in the study. Coronary plaques were
      found in 46 slices on both CTA and MRI. Plaques were classified to 3 groups based
      on CTA: calcified plaques (n = 11), soft plaques (n = 23), and mixed plaques (n =
      12). In MRI, the plaque burden, maximal wall thickness, SNR, and CNR in the
      coronary walls containing plaques were greater than in the normal coronary walls
      (0.83 +/- 0.08 vs. 0.73 +/- 0.08, 1.88 +/- 0.51 vs. 1.51 +/- 0.26 mm, 12.95 +/-
      2.78 vs. 9.93 +/- 2.31, and 6.76 +/- 2.52 vs. 3.89 +/- 1.54, respectively; P <
      0.05). The luminal CSA at the plaque was smaller than in normal coronary walls
      (2.50 +/- 1.50 vs. 4.72 +/- 2.28 mm2; P < 0.05). The SNR in the soft plaque was
      significantly greater than in calcified and mixed plaques (P < 0.05).
      CONCLUSIONS: Coronary wall MRI can identify coronary plaques in the proximal and
      middle segments and has the potential to differentiate plaque types based on
      signal intensity.

PMID- 29063038
TI  - Artificial intelligence: Neural network model as the multidisciplinary team
      member in clinical decision support to avoid medical mistakes.
AB  - OBJECTIVE: The continuous uninterrupted feedback system is the essential part of
      any well-organized system. We propose aLYNX concept that is a possibility to use
      an artificial intelligence algorithm or a neural network model in decision-making
      system so as to avoid possible mistakes and to remind the doctors to review
      tactics once more in selected cases. METHOD: aLYNX system includes: registry with
      significant factors, decisions and results; machine learning process based on
      this registry data; the use of the machine learning results as the adviser. We
      show a possibility to build a computer adviser with a neural network model for
      making a choice between coronary aortic bypass surgery (CABG) and percutaneous
      coronary intervention (PCI) in order to achieve a higher 5-year survival rate in
      patients with angina based on the experience of 5107 patients. RESULTS: The
      neural network was trained by 4679 patients who achieved 5-year survival. Among
      them, 2390 patients underwent PCI and 2289 CABG. After training, the correlation
      coefficient (r) of the network was 0.74 for training, 0.67 for validation, 0.71
      for test and 0.73 for total. Simulation of the neural network function has been
      performed after training in the two groups of patients with known 5-year outcome.
      The disagreement rate was significantly higher in the dead patient group than
      that in the survivor group between neural network model and heart team [16.8%
      (787/4679) vs. 20.3% (87/428), P = 0.065)]. CONCLUSION: The study shows the
      possibility to build a computer adviser with a neural network model for making a
      choice between CABG and PCI in order to achieve a higher 5-year survival rate in
      patients with angina.

PMID- 29063039
TI  - The correlation between white matter hyperintensity and balance disorder and fall
      risk: An observational, prospective cohort study.
AB  - OBJECTIVE: The presence of an association between white matter hyperintensity
      (WMH) and the risk of falls in older people is uncertain, with little supporting
      prospective evidence available at present. We aimed to determine whether WMH was
      associated with dysfunctions of balance and gait, and other sensorimotor factors
      leading to falls, and the independent factors related to falls in older Chinese
      people. The protective effect of exercise against falls was also addressed.
      METHODS: In a representative sample of hospital-based individuals aged 50 years
      and older in China, the patients' history of falls, magnetic resonance imaging
      data, scores on the 9-item Berg Balance Scale (BBS-9) test and timed up-and-go
      test (TUGT), and sensorimotor measures of computerized dynamic posturography
      (CDP) were analyzed. Incident falls were recorded prospectively over a 12-month
      period. Using regression modeling, the association between the risk of falls and
      baseline WMH was estimated. RESULTS: Only individuals with severe WMH were at an
      increased risk of falls, and CDP was more sensitive than BBS-9 in detecting WMH
      related balance and gait dysfunction. However, WMH was not an independent
      predictor of falls. Taller height and overweight or obese body habitus were
      identified as novel protective factors for falls. Female, fall history, and
      increased TUGT score were identified as independent risk factors for falls in
      older Chinese people. CONCLUSION: Although WMH was associated with an increased
      risk of falls, it was not an independent predictor.

PMID- 29063041
TI  - Supraventricular tachycardia with alternating QRS morphology and cycle length.

PMID- 29063040
TI  - Intraoperative high-field magnetic resonance imaging, multimodal neuronavigation,
      and intraoperative electrophysiological monitoring-guided surgery for treating
      supratentorial cavernomas.
AB  - OBJECTIVE: To determine the beneficial effects of intraoperative high-field
      magnetic resonance imaging (MRI), multimodal neuronavigation, and intraoperative
      electrophysiological monitoring-guided surgery for treating supratentorial
      cavernomas. METHODS: Twelve patients with 13 supratentorial cavernomas were
      prospectively enrolled and operated while using a 1.5 T intraoperative MRI,
      multimodal neuronavigation, and intraoperative electrophysiological monitoring.
      All cavernomas were deeply located in subcortical areas or involved critical
      areas. Intraoperative high-field MRIs were obtained for the intraoperative
      "visualization" of surrounding eloquent structures, "brain shift" corrections,
      and navigational plan updates. RESULTS: All cavernomas were successfully resected
      with guidance from intraoperative MRI, multimodal neuronavigation, and
      intraoperative electrophysiological monitoring. In 5 cases with supratentorial
      cavernomas, intraoperative "brain shift" severely deterred locating of the
      lesions; however, intraoperative MRI facilitated precise locating of these
      lesions. During long-term (>3 months) follow-up, some or all presenting signs and
      symptoms improved or resolved in 4 cases, but were unchanged in 7 patients.
      CONCLUSIONS: Intraoperative high-field MRI, multimodal neuronavigation, and
      intraoperative electrophysiological monitoring are helpful in surgeries for the
      treatment of small deeply seated subcortical cavernomas.

PMID- 29063042
TI  - Diagnosis, prevention and management of gestational diabetes mellitus.

PMID- 29063043
TI  - The importance and strategy of diabetes prevention.
AB  - Diabetes has become one of the largest public health problems to date. Decreased
      physical activity, overnutrition, and nutrition transitions caused by changes in
      lifestyle contribute to the increasing incidence of chronic metabolic diseases as
      well as deaths related to them. The shift from undernutrition to overnutrition
      indicates that chronic diseases of affluence have become a public health problem;
      hence, sustainable health-related goals have been developed for the prevention of
      these diseases. Environmental factors and the gut microbiota influence metabolism
      in the human body. Several studies have proven that lifestyle interventions can
      effectively deter the progression of diabetes in individuals with impaired
      glucose tolerance. If the window of prevention is shifted earlier, diabetes may
      become a fortuitous event. Effective prevention needs high attention from the
      government and the participation of all citizens. Concrete scientific and
      reasonable measures also need to be developed by experts and scholars.

PMID- 29063044
TI  - Exercise and its role in gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) refers to diabetes diagnosed in the second or
      third trimester of pregnancy that is not clearly either type 1 or type 2
      diabetes. GDM is a common medical complication in pregnancy that has been rapidly
      increasing worldwide. GDM is associated with both short- and long-term health
      issues for both mothers and offspring. Consistent with type 2 diabetes,
      peripheral insulin resistance contributes to the hyperglycemia associated with
      GDM. Accordingly, it is important to identify strategies to reduce the insulin
      resistance associated with GDM. To date, observational studies have shown that
      exercise can be a non-invasive therapeutic option for preventing and managing GDM
      that can be readily applied to the antenatal population. However, the relevant
      mechanisms for these outcomes are yet to be fully elucidated. The present review
      aimed to explain the potential mechanisms of exercise from the perspective of
      reducing the insulin resistance, which is the root cause of GDM. Exercise
      recommendations and opinions of exercise during pregnancy are briefly summarized.

PMID- 29063045
TI  - KRAS-related noncoding RNAs in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor overall
      prognosis. However, curative resection during the early stages of the disease can
      greatly improve survival rates, highlighting the importance of early screening
      and detection. Studies of noncoding RNAs, primarily microRNAs (miRNAs) and long
      noncoding RNAs (lncRNAs), provide important insights into strategies for the
      early detection of KRAS-driven PDAC. Here, we summarize our studies and review
      current reports on research investigating KRAS-related miRNAs and lncRNAs,
      emphasizing their aberrant expression, mechanisms, carcinogenic effects, and
      prognostic and predictive capacities in PDAC.

PMID- 29063046
TI  - Circulating free DNA in the era of precision oncology: Pre- and post-analytical
      concerns.
AB  - Cancer treatment has entered the era of precision medicine, where knowledge of a
      patient's genetic profile is used to facilitate early diagnosis, drug selection,
      prognosis, prediction of drug responsiveness, the onset of secondary resistance,
      and relapse. Circulating free DNA (cfDNA) has emerged as an ideal source of
      genetic information for cancer patients, and numerous studies have explored its
      validity in various clinical applications. However, clinical implementation of
      cfDNA-based tests has been slow. In this review, we addressed some of the pre-
      and post-analytical issues regarding cfDNA tests. First, we summarized the
      characteristics of cfDNA and reviewed the methods used to identify tumor-derived
      cfDNA from the pool of total cfDNA. Second, we described the procedures used to
      extract cfDNA, which have a great impact on representativeness and yield.
      Finally, we discussed our thoughts on the validation of cfDNA-based tests and the
      reporting of test results amid drastic limitations.

PMID- 29063047
TI  - Data analysis in the post-genome-wide association study era.
AB  - Since the first report of a genome-wide association study (GWAS) on human age
      related macular degeneration, GWAS has successfully been used to discover genetic
      variants for a variety of complex human diseases and/or traits, and thousands of
      associated loci have been identified. However, the underlying mechanisms for
      these loci remain largely unknown. To make these GWAS findings more useful, it is
      necessary to perform in-depth data mining. The data analysis in the post-GWAS era
      will include the following aspects: fine-mapping of susceptibility regions to
      identify susceptibility genes for elucidating the biological mechanism of action;
      joint analysis of susceptibility genes in different diseases; integration of
      GWAS, transcriptome, and epigenetic data to analyze expression and methylation
      quantitative trait loci at the whole-genome level, and find single-nucleotide
      polymorphisms that influence gene expression and DNA methylation; genome-wide
      association analysis of disease-related DNA copy number variations. Applying
      these strategies and methods will serve to strengthen GWAS data to enhance the
      utility and significance of GWAS in improving understanding of the genetics of
      complex diseases or traits and translate these findings for clinical
      applications.

PMID- 29063048
TI  - Frequent exercise: A healthy habit or a behavioral addiction?
AB  - It is well known that regular physical activity helps improve overall health and
      fitness and reduces the risk of many chronic diseases. However, excessive
      exercise might be harmful. Exercise addiction (EA) is a pattern of uncontrolled
      exercise that involves a craving for overwhelming exercise with addictive
      attributes. So far, little is known about this unique behavioral addiction. The
      aim of the current study is to introduce the diagnosis and assessment of EA, and
      to summarize several developing theoretical models. Eating disorders, body image
      disorder, low self-esteem, and high narcissism are related to high risk of EA.
      The paper also discusses the distinction between EA and highly involved physical
      activity.

PMID- 29063049
TI  - Preoperative serum lipid profile and outcome in nonmetastatic colorectal cancer.
AB  - OBJECTIVE: A large portion of non-metastatic colorectal cancers (non-mCRCs) recur
      after curative surgery. In addition to the traditional tumor-related factors,
      host-related factors are also required to accurately predict prognosis. A few
      studies have shown an association between the serum lipid profile and the
      survival and treatment response of patients with colorectal cancer. METHODS: We
      retrospectively evaluated the prognostic significance of the preoperative serum
      lipid profile [total cholesterol (TC), triglyceride (TG), low-density lipoprotein
      cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] in
      patients with non-mCRC treated with curative surgery. The Spearman rank
      correlation test was used to analyze associations between lipid levels and
      categorical variables. Lipid levels were modeled as four equal-sized quartiles
      based on the distribution among the whole cohort. Kaplan-Meier curves were used
      to estimate survival probabilities, and the log-rank test was used to detect
      differences between them. Multivariate fractional polynomial (MFP) analysis was
      used to model any non-linear effects and avoid categorization. To evaluate the
      added prognostic value of lipids, the predictive power of two models (with and
      without lipids as covariates) was compared by using Harrell's C-statistic and the
      Akaike information criterion (AIC). RESULTS: A total of 266 patients with non
      mCRC were enrolled in the present study. Spearman rank correlation test showed
      that TG levels inversely correlated with N stage (r = -0.20, P = 0.00) and Tumor
      Node-Metastasis (TNM) stage (r = -0.19, P = 0.00). HDL-C levels positively
      correlated with perineural invasion (PNI) (r = 0.15, P = 0.02), and LDL-C levels
      inversely correlated with lymphovascular invasion (LVI) (r = -0.12, P = 0.04).
      None of the four lipids predicted overall survival (OS) in univariate or
      multivariate analyses adjusted for age, gender, T stage, N stage, TNM stage,
      histological grade, tumor deposits, LVI, PNI, and adjuvant treatment (all P >
      0.05). In agreement, the Kaplan-Meier curves for OS according to the lipid
      quartiles were not significantly different, as confirmed by the log-rank test
      (all P > 0.05). MFP analysis also found no significant associations between lipid
      levels and OS (all P > 0.05). A prognostic model that included lipids had a
      higher Harrell's C-statistic and a lower AIC value than did a model that did not
      include lipids (for Harrell's C-statistic: 0.82 vs. 0.77; for AIC: 398 vs. 432).
      CONCLUSION: Measuring preoperative serum lipid levels may be a simple and cost
      effective way of increasing prognostic accuracy in patients with non-mCRC treated
      with curative surgery.

PMID- 29063050
TI  - Management of symptomatic caliceal diverticular calculi: Minimally invasive
      percutaneous nephrolithotomy versus flexible ureterorenoscopy.
AB  - OBJECTIVE: To retrospectively evaluate appropriate treatment for patients with
      symptomatic caliceal diverticular calculi, by comparing the therapeutic outcomes
      for those undergoing minimally invasive percutaneous nephrolithotomy (MPCNL) and
      flexible ureterorenoscopy (F-URS). METHODS: From March 2009 to May 2014, 36
      consecutive patients with caliceal diverticular calculi were divided into 2
      groups: 21 patients underwent MPCNL, and 15 were treated by F-URS. All procedures
      were performed by one surgical group, which ensured relatively constant
      parameters. Patient characteristics, operative time, hospital stay after surgery,
      stone-free rate, symptomatic improvement rate, complications, diverticular
      obliteration, and stone composition were analyzed retrospectively in the 2
      groups. RESULTS: Patient preoperative variables were comparable between the two
      groups, with no significant difference (P > 0.05). Mean operative time was 136.9
      +/- 22.8 min in the MPCNL group and 117.3 +/- 24.3 min in the F-URS group (P =
      0.019). Hospital stay was significantly longer in the MPCNL group than in the F
      URS group (9.4 +/- 3.1 vs. 6.9 +/- 2.1 days, P = 0.010). The stone-free rates
      after MPCNL and F-URS were 90.5% (19/21) and 60.0% (9/15), respectively (P =
      0.046). Additionally, 71.4% (15/21) of patients in the MPCNL group and 46.7%
      (7/15) of patients in the F-URS group had symptomatic improvement at the 6-month
      follow-up (P = 0.175); the rates of complications in the 2 groups were 19.0%
      (4/21) and 13.3% (2/15), respectively (P = 0.650). Complete diverticular
      obliteration was achieved in 16 (76.2%) cases in the MPCNL group and 5 (33.3%)
      cases in the F-URS group (P = 0.017). The distributions of calcium oxalate and
      hydroxyapatite in the stones were 66.7% (14/21) and 33.3% (7/21), respectively,
      in the MPCNL group; however, the distributions in the F-URS group were 46.7%
      (7/15) and 53.3% (8/15), respectively (P = 0.310). CONCLUSION: MPCNL is an
      effective method for the treatment of caliceal diverticular calculi. However, F
      URS is an alternative technique in selected patients with a patent infundibulum,
      despite lower stone-free rates than with MPCNL. Fulguration of the diverticular
      lining with a high-power holmium laser and permitting the cavity to collapse are
      useful to increase the chance of diverticular obliteration.

PMID- 29063051
TI  - Advancements in next-generation sequencing for diagnosis and treatment of non
      small-cell lung cancer.

PMID- 29063052
TI  - Quantitative magnetic resonance imaging biomarkers in oncological clinical
      trials: Current techniques and standardization challenges.
AB  - Radiological imaging plays an important role in oncological trials to provide
      imaging biomarkers for disease staging, stratifying patients, defining dose
      setting, and evaluating the safety and efficacy of new candidate drugs and
      innovative treatment. This paper reviews the techniques of most commonly used
      quantitative magnetic resonance imaging (qMRI) biomarkers (dynamic contrast
      enhanced, dynamic susceptibility contrast, and diffusion weighted imaging) and
      their applications in oncological trials. Challenges of incorporating qMRI
      biomarkers in oncological trials are discussed including understanding biological
      mechanisms revealed by MRI biomarkers, consideration of rigorous trial design and
      standardized implementation of qMRI protocols.

PMID- 29063054
TI  - Revision of the concept of anti-angiogenesis and its applications in tumor
      treatment.
AB  - Anti-angiogenesis therapy, by blocking formation of new blood vessels in tumors,
      is the standard-of-care therapy for various cancer types. The classic concept of
      anti-angiogenesis is expected to turn a tumor into a "dormant" disease. However,
      the combination of anti-angiogenesis agents with conventional therapeutics has
      generally produced only modest survival benefits for cancer patients in clinical
      trials. Therefore, the concept and applications of anti-angiogenesis have evolved
      dramatically along with lessons learned from recent clinical experience. In this
      article, we will discuss the revised concept of anti-angiogenesis therapy and the
      applications of anti-angiogenesis drugs, and focus particularly on how to utilize
      current anti-angiogenesis agents and develop new approaches to provide more
      benefits to patients with cancer.

PMID- 29063053
TI  - Management of breast cancer brain metastases: Focus on human epidermal growth
      factor receptor 2-positive breast cancer.
AB  - After the introduction of trastuzumab, a monoclonal antibody that binds to human
      epidermal growth factor receptor 2 (HER2), the overall survival (OS) among
      patients with HER2-positive breast cancer has been substantially improved.
      However, among these patients, the incidence of brain metastases (BM) has been
      increasing and an increased proportion of them have died of intracranial
      progression, which makes HER2-positive breast cancer brain metastases (BCBM) a
      critical issue of concern. For local control of limited BM, stereotactic
      radiosurgery (SRS) and surgical resection are available modalities with different
      clinical indications. Postoperative or preoperative radiation is usually
      delivered in conjunction with surgical resection to boost local control. Adjuvant
      whole-brain radiotherapy (WBRT) should be deferred for limited BM because of its
      impairment of neurocognitive function while having no benefit for OS. Although
      WBRT is still the standard treatment for local control of diffuse BM, SRS is a
      promising treatment for diffuse BM as the technique continues to improve.
      Although large molecules have difficulty crossing the blood brain barrier,
      trastuzumab-containing regimens are critical for treating HER2-positive BCBM
      patients because they significantly prolong OS. Tyrosine kinase inhibitors are
      more capable of crossing into the brain and they have been shown to be beneficial
      for treating BM in HER2-positive patients, especially lapatinib combined with
      capecitabine. The antiangiogenic agent, bevacizumab, can be applied in the HER2
      positive BCBM scenario as well. In this review, we also discuss several
      strategies for delivering drugs into the central nervous system and several
      microRNAs that have the potential to become biomarkers of BCBM.

PMID- 29063055
TI  - Can axillary radiotherapy replace axillary dissection for patients with positive
      sentinel nodes? A systematic review and meta-analysis.
AB  - OBJECTIVE: To compare the efficacy of axillary radiotherapy (ART) with that of
      completion axillary lymph node dissection (cALND) in clinically node-negative
      breast cancer patients with a positive sentinel lymph node. METHODS: A literature
      search was performed in PubMed, EMBASE and Cochrane Library by using the search
      terms "breast cancer", "sentinel lymph node biopsy", "axillary radiotherapy" or
      "regional node irradiation" for articles published between 2004 and 2016. Only
      randomized controlled trials that included patients with positive sentinel nodes
      were included in the meta-analysis. RESULTS: Two randomized controlled trials and
      three retrospective studies were identified. The reported overall survival rate
      (hazard ratio [HR] = 1.09, 95% confidence interval [CI]: 0.75-1.43, P = 0.365),
      disease-free survival rate (HR = 1.01, 95% CI: 0.58-1.45, P = 0.144), and
      axillary recurrence rate (1.2% and 0.4%, and 1.3% and 0.8%, respectively) were
      similar in both groups. The absence of knowledge on the extent of nodal
      involvement in the ART group appeared to have no major impact on the
      administration of adjuvant systemic therapy. CONCLUSIONS: ART is not inferior to
      cALND in the patients with clinically node-negative breast cancer who had a
      positive sentinel lymph node. Information obtained by using cALND after SLNB may
      have no major impact on the administration of adjuvant systemic therapy.

PMID- 29063058
TI  - New guidelines and evidence for prevention and treatment of dyslipidemia and
      atherosclerotic cardiovascular disease in China.

PMID- 29063057
TI  - Clinical epidemiological survey of gallbladder carcinoma in northwestern China,
      2009-2013: 2379 cases in 17 centers.
AB  - OBJECTIVE: To analyze the clinical epidemiological characteristics of patients
      with gallbladder carcinoma recruited from 17 hospitals in five northwestern
      provinces of China (Shaanxi Province, Gansu Province, Qinghai Province, Ningxia
      Hui Autonomous Region, and Xinjiang Uygur Autonomous Region) from 2009 to 2013,
      and to summarize the clinical diagnosis and treatment data of gallbladder
      carcinoma. METHODS: Clinical information of 2379 patients with gallbladder
      carcinoma from 17 hospitals in five northwestern provinces of China was
      retrospectively collected and analyzed using the "Questionnaire for Gallbladder
      Carcinoma Patients in Northwestern Area of China." All information was verified
      with EpiData software and analyzed with SPSS 13.0 software. RESULTS: (1)
      Gallbladder carcinoma accounted for 2.7% (2379/86,609) of all biliary tract
      diseases during the study period, which was significantly higher than that from
      1986 to 1998 (P < 0.001). (2) Gallbladder carcinoma was more prone to occur in
      elderly women. The male:female incidence ratio was 1.0:2.1, the average age of
      onset of disease was 63.7 +/- 11.3 years, and the incidence was higher in farmers
      than in other occupational groups. (3) A total of 57.2% (1360/2379) of patients
      with gallbladder carcinoma also had gallstones. (4) Abdominal pain (1796/2379,
      75.5%) and jaundice (727/2379, 30.6%) were the most common clinical
      manifestations, 81.2% (1527/1881) were positive in those receiving B ultrasound
      examinations and 90.7% (1567/1727) were positive in those undergoing computed
      tomography, and 64.5% (1124/1742) of patients with gallbladder carcinoma were
      positive for carbohydrate antigen (CA) 19-9. (5) The pathological type of
      gallbladder carcinoma was mainly moderately and poorly differentiated
      adenocarcinoma with a high degree of malignancy. At admission, 55.1% (1091/1981)
      of patients had stage IV cancer among patients with TNM staging information;
      55.9% (1331/2379) had lymphatic metastasis, 29.7% (706/2379) had bile duct
      metastasis, and 53.1% (1263/2379) had liver metastasis. (6) A total of 283
      patients (283/2379, 11.9%) had incidentally detected gallbladder carcinoma. (7)
      The rate of radical surgical resection was 30.4% (723/2379). CONCLUSION: The
      proportion of gallbladder carcinoma in biliary tract diseases in the northwestern
      area of China was significantly higher from 2009 to 2013 than from 1986 to 1998.
      Gallbladder carcinoma was common in older women and mainly diagnosed at an
      advanced stage. Compared with other surveys in different regions, the rate of
      metastasis in this survey was high, leading to a low resection rate. Populations
      at high risk should undergo B-ultrasound examinations at regular follow-up
      intervals to increase the rate of early diagnosis of gallbladder carcinoma.

PMID- 29063059
TI  - Integrated medical rehabilitation delivery in China.
AB  - Currently, China has a growing need for rehabilitative care; however,
      rehabilitative care has been underdeveloped for decades. Since the end of 2010,
      pilot programs in 46 cities (districts) of 14 provinces have been initiated by
      the Ministry of Health in China to establish formal arrangements for facilitating
      the delivery of continuous medical rehabilitative care for local communities.
      After 2 years of pilot work, an evaluation was conducted by researchers. This
      paper reviews the current status of rehabilitative care in China and discusses
      the findings of the nationwide pilot program on the integrated rehabilitative
      service. Some key mechanisms and main issues were identified after analyzing the
      preliminary outcomes of some of the pilot programs.

PMID- 29063056
TI  - Comparison of 627 patients with right- and left-sided colon cancer in China:
      Differences in clinicopathology, recurrence, and survival.
AB  - OBJECTIVE: Recent studies have reported increased mortality for right-sided colon
      cancers; however, the results are conflicting for different stage tumors. We
      examined the differences in clinicopathology between right- and left-sided colon
      cancers and the relationships between colon cancer location (right- and left
      side) and 5-year disease-free survival (DFS) and overall survival (OS). METHODS:
      We identified patients from 2005 to 2008 with stage II/III colon cancer who
      underwent surgery for curative intent. We explored the impact of the tumor
      location on the postoperative DFS and OS using univariate and multivariate
      analyses. RESULTS: Of 627 patients, 50.6% (317/627) had right-sided colon cancer.
      These patients were more likely to have weight loss, second primary tumor,
      elevated preoperative carbohydrate antigen 19-9 (CA19-9), increased incidence of
      non-adenocarcinoma, more poorly differentiated tumors, vascular invasion,
      defective mismatch repair, and a lighter smoking history (P < 0.05). Right-sided
      colon cancer had a higher recurrence incidence compared with left-sided cancer
      (30.6% vs. 23.2%, P = 0.037), particularly with multiple metastatic sites in the
      first recurrence (17.5% vs. 5.6%, P = 0.020). Kaplan-Meier survival curves
      demonstrated a significant difference in the 5-year DFS rate between right- and
      left-sided cancers across all stages (68.1% vs. 75.2%, P = 0.043). However, there
      was no significant difference in the 5-year OS rate between the two groups (73.8%
      vs. 79.0%, P = 0.103). Subgroup analysis demonstrated that patients with left
      sided colon cancer had a significantly better 5-year DFS and OS rates compared
      with those with right-sided disease at stage III (64.3% vs. 46.8%, P = 0.002;
      69.5% vs. 53.5%, P = 0.006, respectively); there were no significant differences
      in the 5-year DFS and OS rates at stage II (85.2% vs. 85.9%, P = 0.819; 89.8% vs.
      88.5%, P = 0.803, respectively). Adjusted Cox regression analysis showed no
      significant differences in the 5-year OS and DFS rates for stage II [hazard ratio
      (HR) = 1.203, 95% confidence interval (CI): 0.605-2.391, P = 0.598; HR = 0.980,
      95% CI: 0.542-1.774, P = 0.948, respectively] or all stages combined (HR = 0.867,
      95% CI: 0.613-1.227, P = 0.421; HR = 0.832, 95% CI: 0.606-1.142, P = 0.255,
      respectively). However, stage III left-sided cancer had higher 5-year OS and DFS
      rates (HR = 0.626, 95% CI: 0.414-0.948, P = 0.027; HR = 0.630, 95% CI: 0.428
      0.926, P = 0.019, respectively). CONCLUSION: We found that right- and left-sided
      colon cancers had significantly different clinicopathological characteristics.
      Right-sided colon cancer had a higher incidence of recurrence than left-sided
      disease. Patients with stage III right-sided colon cancer had a worse prognosis
      compared with those with stage III left-sided colon cancer.

PMID- 29063060
TI  - The growth of chronic conditions: Search for solutions to the problem.
AB  - The chronic conditions growth is determined by an increase of cases of adaptive
      system imbalance following a recent disease. One of its most significant causes
      is decrease of crisis importance (a stage of disease) as a moderator of a
      qualitative changeover of an adaptive system. The contemporary treatment methods
      increase efficiency of pre-crises adaptive responses, but simultaneously they
      equalize the crisis to a level, which is insufficient for complete after-crisis
      alignment of body defenses. But the crisis is the very key to a solution to a
      chronic conditions problem. One of the ways of the problem solving is medical
      interventions, which cause sparing provocation crisis and a successive changeover
      of an adaptive system. Based on this it is worth reviewing critically, studying
      and developing the existing experience of bio-regulatory therapy, where the
      principle of sparing provocation is often used. The new term definitions, such as
      "medical intervention", "health problems", "crisis" are described in terms of
      biomedicine. The patients and physicians should be motivated to deal with chronic
      conditions correction and the aforesaid sets new tasks before a health care
      system.

PMID- 29063061
TI  - Association between circulating oxidized low-density lipoprotein and
      atherosclerotic cardiovascular disease.
AB  - Atherosclerosis is a chronic, progressive disease which eventually leads to
      coronary heart disease (CHD), ischemic stroke and other atherosclerotic
      cardiovascular disease (ASCVD). Numerous studies have demonstrated an atherogenic
      role of oxidized low-density lipoprotein (ox-LDL) in the progression of ASCVD.
      This article briefly reviews the atherogenic mechanism of ox-LDL, the methods of
      measuring ox-LDL in the circulation, effect of medical therapy and life-style
      modification on ox-LDL level, and the association between circulating ox-LDL and
      atherosclerosis, including clinical ASCVD events and subclinical atherosclerosis,
      in observational studies.

PMID- 29063062
TI  - Association between the rs1042522 polymorphism in TP53 and prostate cancer risk:
      An updated meta-analysis.
AB  - OBJECTIVE: The proposal of the present study was to investigate whether the TP53
      rs1042522 polymorphism confers susceptibility to prostate cancer (PCa), by
      performing an updated meta-analysis. METHODS: Eligible publications investigating
      the association between the TP53 rs1042522 polymorphism and PCa susceptibility
      were selected from PubMed, Google Scholar, and Web of Science. We used STATA 12.0
      software to conduct the analyses. Odds ratio (OR) with 95% confidence interval
      (CI) was calculated. RESULTS: A total of 17 case-control studies were retrieved
      reporting a total of 2683 cases and 2981 controls. However, no significant
      association was uncovered between the TP53 rs1042522 polymorphism and PCa
      susceptibility in the overall population under the five genetic models. In the
      stratification analysis by source of control, an increased susceptibility to PCa
      was identified in the population-based (P-B) group (CG vs. GG: OR = 1.48, 95% CI:
      1.24-1.77, P < 0.01; CC/CG vs. GG: OR = 1.32, 95% CI: 1.12-1.57, P < 0.01),
      whereas a decreased susceptibility was uncovered in the hospital-based (H-B)
      group (CG vs. GG: OR = 0.67, 95% CI: 0.46-0.96, P = 0.03; CC/CG vs. GG: OR =
      0.67, 95% CI: 0.46-0.99, P = 0.04) under heterozygous and dominant model.
      CONCLUSION: This study did not find an association between the TP53 rs1042522
      polymorphism and PCa susceptibility in the overall population and corresponding
      subgroup analyses except in the stratification analysis by source of control. The
      results suggest that the TP53 rs1042522 polymorphism is not a risk factor for
      PCa.

PMID- 29063063
TI  - Effect of type 2 diabetic serum on the behavior of Wharton's jelly-derived
      mesenchymal stem cells in vitro.
AB  - OBJECTIVE: Wharton jelly-derived mesenchymal stem cells (WJMSCs) exhibit
      multilineage differentiation potential and can be used to treat multiple organs.
      However, diabetes affects the repair capability of MSCs. The aim of this study
      was to evaluate the effect of diabetic patient-derived serum on WJMSC behavior.
      METHODS: WJMSCs at passage 3 were treated with serum derived from type 2 diabetic
      patients. WJMSCs were characterized for surface markers expression by using
      immunocytochemistry technique. The effects on cell viability, proliferation, cell
      death rate, and vascular endothelial growth factor level were assessed by crystal
      violet staining, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      (MTT) assay, lactate dehydrogenase assay, and enzyme-linked immuno-sorbent assay,
      respectively. Oxidative stress was assessed by the estimation of free radical
      species malondialdehyde (MDA) and enzymes glutathione (GSH), catalase, and
      superoxide dismutase (SOD). RESULTS: WJMSCs isolated in this study were positive
      for CD29, CD49, CD73, CD90, CD105, and SSEA4 and negative for CD45 and CD34.
      Under diabetic stress conditions, WJMSCs showed low viability and high lactate
      dehydrogenase release. A low level of vascular endothelial growth factor was also
      observed after diabetic serum treatment. Antioxidant level was also lower in
      diabetic serum-treated WJMSCs compared to in normal serum-treated WJMSCs.
      CONCLUSION: The results of the present study suggest that pre-treatment of WJMSCs
      with type 2 diabetic serum decreases the survival of WJMSCs. The findings of this
      study provide insight into diabetes-induced harmful effects on WJMSCs.

PMID- 29063064
TI  - Burden of chronic illness and associated disabilities in Bangladesh: Evidence
      from the Household Income and Expenditure Survey.
AB  - OBJECTIVE: The purpose of this study was to investigate the distribution of
      chronic illness and associated disability, out-of-pocket payment (OOPP), and
      other related factors using survey data from Bangladesh. METHODS: This study
      analyzed Bangladesh Household Income and Expenditure Survey data that include
      socio-economic and demographic data, such as consumption, expenditures, and
      assets, along with information regarding chronic illness and disability. Multiple
      linear regression models were used to identify factors significantly associated
      with OOPP. Furthermore, a binary Logistic regression model was employed to assess
      the association of the explanatory variables with disability status. RESULTS: A
      higher prevalence of chronic illness was found for those with chronic gastritis
      (18.70%), and 41.92% of the population had at least one side disability. The
      average OOPP healthcare expenditure for chronic illness was estimated to be
      US$7.59. Higher OOPP was found among the upper 2 wealth quintiles. Overall OOPP
      health expenditure was significantly higher among individuals with an associated
      disability (P < 0.001). The likelihood of having an associated disability was
      higher among those individuals with a lower education level (OR = 2.36, 95% CI:
      1.95-4.06), those who not earning an income (OR = 2.85, 95% CI: 2.53-3.21), those
      who did not seek care (OR = 1.73, 95% CI: 1.57-1.90), those who sought care from
      a pharmacy (OR = 8.91, 95% CI: 7.38-10.74), and those in the lowest wealth
      quintile (OR = 7.21, 95% CI: 6.41-8.12). CONCLUSIONS: The high OOPP illustrates
      the necessity of financial risk protection for the population at low socio
      economic status. Therefore, we recommend that the government strengthen the
      healthcare system with appropriate support directed to the rural and elderly
      populations.

PMID- 29063065
TI  - Paradoxical embolism: Experiences from a single center.
AB  - OBJECTIVE: To present our treatment experiences and the follow-up data of
      patients with paradoxical embolism (PDE). METHODS: The clinical characteristics,
      management, and follow-up data of all included patients who were diagnosed with
      PDE at Fuwai Hospital from January 1994 to October 2015 were recorded. RESULTS:
      Twelve patients were included; all had a pulmonary embolism, and 8 had deep
      venous thrombosis. The artery embolisms involved the cerebral artery (7
      patients), renal artery (2 patients), mesentery artery (2 patients), popliteal
      artery (1 patient), descending aorta thrombus (1 patient), and thrombus-straddled
      patent foramen ovale (PFO) (1 patient). PFO was found in 3 cases. One patient
      underwent thrombectomy and PFO closure; Six patients received thrombolysis; and 3
      patients were implanted with a vena cava filter. Long-term anticoagulation with
      warfarin was recommended for each patient. One patient died from ventricular
      fibrillation despite cardiopulmonary resuscitation. Eleven patients were
      discharged with improvements. No late mortality occurred in 8 patients with a
      complete follow-up of 10.6-17.7 years. One had a recurrent deep venous
      thrombosis. No patient had a recurrent pulmonary or arterial embolism. Two
      patients changed their treatment from warfarin to aspirin; others remained on
      warfarin. Only 1 case had an occasional gum bleeding. CONCLUSIONS: PDE treatment
      including thrombolysis, anticoagulation, and embolectomy should be
      individualized. We recommend long-term anticoagulation therapy to prevent the
      recurrence of PDE, especially to those with an intracardiac communication or
      persistent risk factors for re-thrombosis.

PMID- 29063067
TI  - China's Medium-to-Long Term Plan for the Prevention and Treatment of Chronic
      Diseases (2017-2025) under the Healthy China Initiative.

PMID- 29063066
TI  - Stroke screening and health-related physical fitness testing in medical staff
      members in Urumqi, China.
AB  - OBJECTIVE: Stroke is the leading cause of death and disability, and is closely
      related to a lack of exercise. Currently, most Chinese medical staff members lack
      exercise and may be at risk for stroke. We sought to determine the risk factors
      for stroke and study the significance of health-related physical fitness testing
      in stroke prevention among Chinese medical staff members. METHODS: A total of 627
      subjects from Urumqi, Xinjiang, China, were included in the study and a survey
      was conducted from 1st January 2016 to 1st February 2016. Stroke screening and
      health-related physical fitness testing were completed according to the standard
      protocol, and the related data were analyzed. RESULTS: Based on the screening,
      27.6% (n = 173) of the subjects were at high risk for stroke. The top risk
      factors for stroke in these subjects were dyslipidemia, lack of exercise or mild
      physical activity, being overweight or obese, and high blood pressure. Body
      weight, body mass index, body fat, visceral fat area, body fat percentage, and
      basal metabolic rate were significantly higher (P < 0.01) in subjects at high
      risk for stroke than in subjects who were not at high risk. Lung capacity, step
      index, grip test, vertical jump, and sit-up/push-up index were significantly
      lower (P < 0.01) in subjects at high risk for stroke than in subjects who were
      not at high risk. CONCLUSIONS: A large proportion of China's on-the-job medical
      personnel is at high risk for stroke. This may be related to the nature of the
      profession and warrants more attention from the society. The health-related
      physical fitness measurement parameters in subjects at high risk for stroke were
      significantly different from those in subjects who were not at high risk.
      Screening and health-related physical fitness testing in medical staff members
      may contribute to stroke prevention. More rigorous controlled clinical trials
      will be needed in the future.

PMID- 29063068
TI  - Immunoglobulin G4-related kidney disease: Pathogenesis, diagnosis, and treatment.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized clinical
      entity that often involves multiple organs; it is characterized by high levels of
      serum immunoglobulin G4 (IgG4), dense infiltration of IgG4+ cells, and storiform
      fibrosis. Cellular immunity, particularly T cell-mediated immunity, has been
      implicated in the pathogenesis of IgG4-RD. The most frequent renal manifestations
      of IgG4-RD are IgG4-related tubulointerstitial nephritis, membranous
      glomerulonephropathy (MGN), and obstructive nephropathy secondary to urinary
      tract obstruction due to IgG4-related retroperitoneal fibrosis, prostatitis, or
      ureter inflammation. Kidney function impairment can be acute or chronic. In IgG4
      MGN, proteinuria can be in the nephrotic range. The diagnosis of IgG4-related
      kidney disease should not be based solely on serum IgG4 levels or the number of
      tissue-infiltrating IgG4+ plasma cells. Diagnosis should be based on specific
      histopathological findings, confirmed by tissue immunostaining and an appropriate
      clinical context. Steroid treatment is the first-line therapy. For relapsing or
      refractory cases, immunosuppressants could be combined with steroids. In
      hydronephrosis patients, appropriate immunosuppressive therapy could preclude the
      implantation of a double J ureteral catheter.

PMID- 29063069
TI  - Targeting MET in cancer therapy.
AB  - MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF).
      The specific combination of c-MET and HGF activates downstream signaling pathways
      to trigger cell migration, proliferation, and angiogenesis. MET exon 14
      alterations and MET gene amplification play a critical role in the origin of
      cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have
      been evaluated in clinical trials. In patients with advanced non-small cell lung
      cancer, cabozantinib and crizotinib showed clear efficacy with a generally
      tolerable adverse events profile. In gastrointestinal cancers, most phase III
      trials of MET inhibitors showed negative results. In hepatocellular carcinoma,
      based on the encouraging results of some phase II studies, a series of phase III
      trials are currently recruiting patients to access the efficacy and safety of MET
      inhibitors.

PMID- 29063070
TI  - Dietary behaviour changes to improve nutritional quality and health outcomes.
AB  - This narrative review examines the changes required in dietary behaviours to
      address the current global burden of disease resulting from diet-associated
      cardiometabolic dysfunction. Beginning with known relationships between
      nutritional factors and health outcomes, the review identifies a number of
      problems with current dietary behaviours, using examples from the Australian
      context. Implications for practice are then discussed drawing on insights from
      research in dietary trials. From a concerted research effort across the globe,
      the effects of foods, food components and dietary patterns on cardiometabolic
      parameters have been reasonably well exposed. The evidence base for these effects
      underpins dietary guidelines, which aim to meet nutritional requirements and
      protect against cardiometabolic disease. Thus foods recommended in dietary
      guidelines tend to be consistent with research that identifies foods that appear
      protective and those that appear detrimental to health. The need for dietary
      behaviour change is apparent through analyses that have exposed increasing
      consumption of detrimental foods, despite the availability of healthy foods.
      However, behaviour change is a complex area, and where weight loss is also
      required, there is high level evidence that interdisciplinary efforts combining
      diet, physical activity and psychological support are warranted. Insights from
      dietary trials and research indicate that focussing on foods and dietary patterns
      is integral to the specific dietary change required for health outcomes, but
      social and behavioural factors will influence the achievement of these changes.

PMID- 29063071
TI  - Novel strategies halt cardiovascular, diabetes, and cancer strips.
AB  - In this article, we introduce briefly several strategies for preventing
      atherosclerotic cardiovascular disease and promoting healthcare for non
      communicable diseases (NCDs). These novel strategies include four core elements
      of health - sleep, emotion, exercise, and diet - and consist of SEED intervention
      (SEEDi) and E(e)SEEDi due to supplementation of the environment as a core
      element, and Hu's healthy lifestyles intervention (HHLi) which originates from
      E(e)SEED-BasED healthy lifestyles. They are suitable for the early evaluation of
      risk factors, and play a key role in the prevention and management of human NCDs
      when combined with the RT-ABCDEF strategy and the Grade 210 prevention, which
      include obesity-OSA-hypertension syndrome and C-type hypertension, especially in
      halting cardiovascular, diabetes and cancer (CDC) strips we first discovered.
      After successful clinical practice, we may expect our novel strategies for
      controlling these chronic diseases according to the conception of mass prevention
      and treatment.

PMID- 29063072
TI  - Potential role of thymosin beta 4 in the treatment of nonalcoholic fatty liver
      disease.
AB  - As a result of increased prevalence of obesity worldwide, non-alcoholic fatty
      liver disease (NAFLD) has become one of the most common causes of chronic liver
      disease. Although most NAFLD cases remain benign, some progress to end-stage
      liver diseases such as cirrhosis and hepatocellular carcinoma. Therefore,
      treatment should be considered for NAFLD patients who are likely to progress to
      nonalcoholic steatohepatitis (NASH) or fibrosis. Thymosin beta 4 (Tbeta4), a G
      actin sequestering peptide, regulates actin polymerization in mammalian cells. In
      addition, studies have reported anti-inflammatory, insulin-sensitizing, and anti
      fibrotic effects of Tbeta4. However, no research has been done to investigate the
      effects of Tbeta4 on NAFLD. Based on the findings above mentioned, we hypothesize
      that Tbeta4 may represent an effective treatment for NAFLD.

PMID- 29063073
TI  - The association between metformin use and colorectal cancer survival among
      patients with diabetes mellitus: An updated meta-analysis.
AB  - OBJECTIVE: Recent studies have reported conflicting results on the correlation
      between metformin use and outcomes in patients with colorectal cancer (CRC). A
      meta-analysis was performed to evaluate the efficacy of metformin therapy on the
      prognosis of CRC patients with type 2 diabetes mellitus (T2DM). METHODS: We
      conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and the
      Web of Science for related articles up to August 2016. Two investigators
      independently identified and extracted information. Pooled risk estimates [hazard
      ratios (HRs)] and 95% confidence intervals (CIs) were calculated using fixed
      effects models. The risk of publication bias was assessed by examining funnel
      plot asymmetry as well as Egger's test and Begg's test. RESULTS: Of 81 articles
      identified, 8 retrospective cohort studies, representing 6098 cases of CRC
      patients with T2DM who used metformin and 4954 cases of CRC patients with T2DM
      who did not use metformin, were included in this meta-analysis. There was no
      significant heterogeneity and quality difference between studies. Metformin users
      had significantly improved overall survival (OS) (HR = 0.82, 95% CI: 0.77-0.87, P
      = 0.000). However, Metformin use cannot affect CRC-specific survival (HR = 0.84,
      95% CI: 0.69-1.02, P = 0.079) compared to non-users. CONCLUSION: This meta
      analysis suggests that metformin use may improve survival among CRC patients with
      T2DM. However, prospective controlled studies are still needed to rigorously
      evaluate the efficacy of metformin as an anti-tumor agent.

PMID- 29063074
TI  - Evaluation of symptoms and risks in stable chronic obstructive pulmonary disease
      patients with radiographic bronchiectasis.
AB  - OBJECTIVE: To investigate the presence of previously undiagnosed radiographic
      bronchiectasis in stable chronic obstructive pulmonary disease (COPD) patients
      using high resolution computed tomography (HRCT) and to evaluate the effect of
      radiographic bronchiectasis on the symptoms and risks in stable COPD patients.
      METHODS: From May 2012 to April 2014, there were 347 patients enrolled in COPD
      database. Data describing the general conditions, the frequency of acute
      exacerbations the year before, COPD assessment test, modified medical research
      council (mMRC) score, spirometric classification, and HRCT were collected. COPD
      patients were classified into two groups: COPD with bronchiectasis and COPD
      without bronchiectasis. The clinical characteristics of both groups were
      compared. RESULTS: Bronchiectasis was presented in 18.4% (n = 64). The proportion
      of smokers, smoking index, and forced expiratory volume in 1 second predicted
      value were 62.5%, 27.3 +/- 13.2, 48.2 +/- 26.4, respectively, in the
      bronchiectasis group, which were lower than those of the group without
      bronchiectasis (82.0%, 32.6 +/- 17.6, and 57.9 +/- 18.8) (P < 0.05).
      Complications, COPD assessment test (CAT) and the rate of CAT >= 10 in the
      bronchiectasis group were 2.8 +/- 1.7,13.6 +/- 7.4 and 26.6%, respectively, which
      were higher than those of the group without bronchiectasis (2.3 +/- 1.5,11.3 +/-
      6.0, and 11.7%) (P < 0.05). The proportion of type D (high-risk more-symptoms) in
      the bronchiectasis group was 50.0%; it was significantly higher than that of
      35.7% in the group without bronchiectasis (P < 0.05). CONCLUSIONS: COPD with
      bronchiectasis is associated with more complications, symptoms, and risks. More
      attention should be paid to the treatment of COPD with bronchiectasis to reduce
      the frequency of exacerbation and improve the health status.

PMID- 29063075
TI  - Analysis of the parathyroid function in maintenance hemodialysis patients from
      Changchun, China.
AB  - OBJECTIVE: To evaluate the parathyroid function in maintenance hemodialysis
      patients from 4 hemodialysis centers and to analyze the cause of the dysfunction.
      METHODS: This cross-sectional study included patients with chronic renal disease
      undergoing maintenance hemodialysis treatment at 4 hemodialysis centers in
      Changchun, China, between March 2014 and August 2015. A total of 337 patients
      were asked to complete a questionnaire including their name, gender, age,
      hemodialysis duration, the use of calcium carbonate and vitamin D3 supplements,
      health education status, hemofiltration frequency, appetite, and education level.
      Serum intact parathyroid hormone (iPTH), phosphorus, total calcium, blood urea
      nitrogen (BUN), and creatinine (Cre) levels were obtained from clinical
      information. Patients with iPTH data were divided into 2 groups: Normal group:
      the patients with an iPTH level < 100 pg/ml (28 subjects); Abnormal group: the
      patients with an iPTH level > 100 pg/ml (136 subjects). Intergroup differences
      were analyzed using the t-test. The enumeration data were analyzed by the chi2
      test. RESULTS: The iPTH levels were not monitored for 173 maintenance
      hemodialysis patients (51.3%) but for 164 patients (48.7%). Of the 164 patients,
      28 (17.1%) had a normal serum iPTH level, while the other 136 (82.9%) had an
      abnormal iPTH level. The maintenance hemodialysis duration and phosphorus levels
      in the Abnormal group were higher than those in the Normal group (P < 0.05). The
      appetites of patients in the Abnormal group were better than those of patients in
      the Normal group (P < 0.05). CONCLUSIONS: A lower proportion of patients on
      hemodialysis had a normal iPTH level. The phosphorus levels of patients on
      hemodialysis should be controlled via dietary interventions.

PMID- 29063077
TI  - Rhenium tricarbonyl complexes of AIE active tetraarylethylene ligands: tuning
      luminescence properties and HSA-specific binding.
AB  - The synthesis and photophysical properties of luminescent Re(i) tricarbonyl
      complexes prepared from bis(pyridyl)- and bis(quinolyl) tetraarylethylene (TAE)
      ligands are reported. Emission wavelengths of the complexes are influenced by
      structural variation in the tetraarylethylene ligands, and several complexes
      display aggregation-induced enhanced emission in aqueous solution. A Re(i)
      complex prepared from an indole-functionalized TAE ligand shows significant
      enhancement in its luminescence intensity accompanied by a remarkable blue shift
      (~95 nm) upon specific binding to site II of human serum albumin.

PMID- 29063076
TI  - Restless legs syndrome secondary to pontine infarction: Clinical analysis of five
      cases.
AB  - OBJECTIVE: Pontine infarction is a common type of stroke in the cerebral deep
      structures, resulting from occlusion of small penetrating arteries, may manifest
      as hemi-paralysis, hemi-sensory deficit, ataxia, vertigo, and bulbar dysfunction,
      but patients presenting with restless legs syndrome (RLS) are extremely rare.
      Herein, we reported five cases with RLS as a major manifestation of pontine
      infarction. METHODS: Five cases of pontine infarction related RLS were collected
      from July 2013 to February 2016. The diagnosis of RLS was made according to
      criteria established by the International RLS Study Group (IRLSSG) in 2003.
      Neurological functions were assessed according to the National Institutes of
      Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Severity of RLS was
      based on the International RLS Rating Scale (IRLS-RS). Sleep quality was assessed
      by Epworth Rating Scale (ERS), and individual emotional and psychological states
      were assessed by Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale
      (HAS). RESULTS: The laboratory data at the onset including hemoglobin, serum
      concentration of homocysteine, blood urea nitrogen (BUN), creatinine,
      electrolytes, and thyroid hormones were normal. The electroencephalogram (EEG),
      lower-extremity somatosensory evoked potential (SEP), and nerve conduction
      velocity (NCV) in four limbs were normal. The average period of follow-up was
      34.60 +/- 12.76 months. The MRI examination showed acute or subacute pontine
      infarction lesions, 3 cases in the rostral inner side, 1 case in the rostral
      lateral and inner side, and 1 case in rostral lateral side. The neurological
      deficits included weakness in 4 cases, contralateral sensory deficit in 1 case,
      and ataxia in 2 cases. All 5 patients presented with symptom of RLS at or soon
      after the onset of infarction and 4 patients experienced uncomfortable sensations
      in the paralyzed limbs contralateral to the ischemic lesion. Their neurological
      deficits improved significantly 2 weeks later, but the symptoms of RLS did not
      resolve. Among them, 3/5 patients were treated with dopaminergic drugs. At the
      end of the follow-up, RLS symptom eventually resolved in 3 patients but persisted
      in two. The IRLS-RS, NIHSS and mRS scores were significantly lower at the onset
      than those at the last follow-up (P = 0.035, 0.024 and 0.049, respectively).
      However, there was no significant difference in the ERS, HDS and HAS scores (P =
      0.477, 0.226 and 0.778, respectively). CONCLUSION: RLS can be an onset
      manifestation of pontine infarction, clinicians should be aware of this potential
      symptom. RLS usually occurs in the paralyzed limbs contralateral to the
      infarction lesion. The pathogenesis still needs further investigation.

PMID- 29063078
TI  - The hydration structure of the heavy-alkalines Rb+ and Cs+ through molecular
      dynamics and X-ray absorption spectroscopy: surface clusters and eccentricity.
AB  - Physicochemical properties of the two heaviest stable alkaline cations, Rb+ and
      Cs+, in water have been examined from classical molecular dynamics (MD)
      simulations. Alkaline cation-water intermolecular potentials have been built from
      ab initio interaction energies of [M(H2O)n]+ clusters. Unlike in the case of
      other monatomic metal cations, the sampling needed the inclusion of surface
      clusters to properly describe the interactions. The first coordination shell is
      found at an average M-O distance of 2.87 A and 3.12 A for Rb+ and Cs+,
      respectively, with coordination numbers of 8 and 10. Structural, dynamical and
      energetic properties are discussed on the basis of the delicate compromise among
      the ion-water and water-water interactions which contribute almost on the same
      foot to the definition of the solvent structure around the ions. A significant
      asymmetry is detected in the Rb+ and Cs+ first hydration shell. Reorientational
      times of first-shell water molecules for Cs+ support a clear structure-breaking
      nature for this cation, whereas the Rb+ values do not differ from pure water
      behavior. Experimental EXAFS and XANES spectra have been compared to simulated
      ones, obtained by means of application of the FEFF code to a set of statistically
      significant structures taken from the MD simulations. Due to the presence of
      multi-excitations in the absorption spectra, theoretical-experimental agreement
      for the EXAFS spectra is reached when the multi-excitations are removed from the
      experimental spectra.

PMID- 29063079
TI  - A microfluidic design to provide a stable and uniform in vitro microenvironment
      for cell culture inspired by the redundancy characteristic of leaf areoles.
AB  - The leaf venation is considered to be an optimal transportation system with the
      mesophyll cells being divided by minor veins into small regions named areoles.
      The transpiration of water in different regions of a leaf fluctuates over time
      making the transportation of water in veins fluctuate as well. However, because
      of the existence of multiple paths provided by the leaf venation network and the
      pits on the walls of the vessels, the pressure field and nutrient concentration
      in the areoles that the mesophyll cells live in are almost uniform. Therefore,
      inspired by such structures, a microfluidic design of a novel cell culture
      chamber has been proposed to obtain a stable and uniform microenvironment. The
      device consists of a novel microchannel system imitating the vessels in the leaf
      venation to transport the culture medium, a cell culture chamber imitating the
      areole and microgaps imitating the pits. The effects of the areole and pit on
      flow fields in the cell culture chamber have been discussed. The results indicate
      that the bio-inspired microfluidic device is a robust platform to provide an in
      vivo like fluidic microenvironment.

PMID- 29063081
TI  - Automated microfluidic platform for systematic studies of colloidal perovskite
      nanocrystals: towards continuous nano-manufacturing.
AB  - Colloidal organic/inorganic metal-halide perovskite nanocrystals have recently
      emerged as a potential low-cost replacement for the semiconductor materials in
      commercial photovoltaics and light emitting diodes. However, unlike III-V and IV
      VI semiconductor nanocrystals, studies of colloidal perovskite nanocrystals have
      yet to develop a fundamental and comprehensive understanding of nucleation and
      growth kinetics. Here, we introduce a modular and automated microfluidic platform
      for the systematic studies of room-temperature synthesized cesium-lead halide
      perovskite nanocrystals. With abundant data collection across the entirety of
      four orders of magnitude reaction time span, we comprehensively characterize
      nanocrystal growth within a modular microfluidic reactor. The developed high
      throughput screening platform features a custom-designed three-port flow cell
      with translational capability for in situ spectral characterization of the in
      flow synthesized perovskite nanocrystals along a tubular microreactor with an
      adjustable length, ranging from 3 cm to 196 cm. The translational flow cell
      allows for sampling of twenty unique residence times at a single equilibrated
      flow rate. The developed technique requires an average total liquid consumption
      of 20 MUL per spectra and as little as 2 MUL at the time of sampling. It may
      continuously sample up to 30 000 unique spectra per day in both single and multi
      phase flow formats. Using the developed plug-and-play microfluidic platform, we
      study the growth of cesium lead trihalide perovskite nanocrystals through in situ
      monitoring of their absorption and emission band-gaps at residence times ranging
      from 100 ms to 17 min. The automated microfluidic platform enables a systematic
      study of the effect of mixing enhancement on the quality of the synthesized
      nanocrystals through a direct comparison between single- and multi-phase flow
      systems at similar reaction time scales. The improved mixing characteristics of
      the multi-phase flow format results in high-quality perovskite nanocrystals with
      kinetically tunable emission wavelength, ranging as much as 25 nm at equivalent
      residence times. Further application of this unique platform would allow rapid
      parameter optimization in the colloidal synthesis of a wide range of
      nanomaterials (e.g., metal or semiconductor), that is directly transferable to
      continuous manufacturing in a numbered-up platform with a similar characteristic
      length scale.

PMID- 29063083
TI  - Sub-nanometre metal clusters for catalytic carbon-carbon and carbon-heteroatom
      cross-coupling reactions.
AB  - Catalytic cross-coupling reactions are fundamental transformations in modern
      organic synthesis. Traditionally based on single-atom transition metal complex
      catalysts, the use of sub-nanometre metal clusters with enhanced redox and
      coordinating properties may lead to more efficient catalysts. Recent developments
      and potential new directions of catalytic sub-nanometre metal clusters for cross
      coupling reactions are briefly discussed here.

PMID- 29063082
TI  - The electron density of delocalized bonds (EDDB) applied for quantifying
      aromaticity.
AB  - In this study the recently developed electron density of delocalized bonds (EDDB)
      is used to define a new measure of aromaticity in molecular rings. The
      relationships between bond-length alternation, electron delocalization and
      diatropicity of the induced ring current are investigated for a test set of
      representative molecular rings by means of correlation and principal component
      analyses involving the most popular aromaticity descriptors based on structural,
      electronic, and magnetic criteria. Additionally, a qualitative comparison is made
      between EDDB and the magnetically induced ring-current density maps from the
      ipsocentric approach for a series of linear acenes. Special emphasis is given to
      the comparative study of the description of cyclic delocalization of electrons in
      a wide range of organic aromatics in terms of the kekulean multicenter index KMCI
      and the newly proposed EDDBk index.

PMID- 29063080
TI  - Studies of copper trafficking in a mouse model of Alzheimer's disease by positron
      emission tomography: comparison of 64Cu acetate and 64CuGTSM.
AB  - Alzheimer's disease can involve brain copper dyshomeostasis. We aimed to
      determine the effect of AD-like pathology on 64Cu trafficking in mice, using
      positron emission tomography (PET imaging), during 24 hours after intravenous
      administration of ionic 64Cu (Cu(ii) acetate) and 64Cu-GTSM (GTSMH2 =
      glyoxalbis(thiosemicarbazone)). Copper trafficking was evaluated in 6-8-month-old
      and 13-15 month-old TASTPM transgenic and wild-type mice, by imaging 0-30 min and
      24-25 h after intravenous administration of 64Cu tracer. Regional 64Cu
      distribution in brains was compared by ex vivo autoradiography to that of amyloid
      beta plaque. 64Cu-acetate showed uptake in, and excretion through, liver and
      kidneys. There was minimal uptake in other tissues by 30 minutes, and little
      further change after 24 h. Radioactivity within brain was focussed in and around
      the ventricles and was significantly greater in younger mice. 64CuGTSM was taken
      up in all tissues by 30 min, remaining high in brain but clearing substantially
      from other tissues by 24 h. Distribution in brain was not localised to specific
      regions. TASTPM mice showed no major changes in global or regional 64Cu brain
      uptake compared to wildtype after administration of 64Cu acetate (unlike 64Cu
      GTSM) but efflux of 64Cu from brain by 24 h was slightly greater in 6-8 month-old
      TASTPM mice than in wildtype controls. Changes in copper trafficking associated
      with Alzheimer's-like pathology after administration of ionic 64Cu are minor
      compared to those observed after administration of 64Cu-GTSM. PET imaging with
      64Cu could help understand changes in brain copper dynamics in AD and underpin
      new clinical diagnostic imaging methods.

PMID- 29063085
TI  - Exploiting a single intramolecular conformational switching Ni-TPP molecule to
      probe charge transfer dynamics at the nanoscale on bare Si(100)-2 * 1.
AB  - Acquiring quantitative information on charge transfer (CT) dynamics at the
      nanoscale remains an important scientific challenge. In particular, CT processes
      in single molecules at surfaces need to be investigated to be properly controlled
      in various devices. To address this issue, the dynamics of switching molecules
      can be exploited. Here, nickel-tetraphenylporphyrin adsorbed on the Si(100)
      surface is used to study the CT process ruling the reversible activation of two
      chiral molecular conformations. Via the electrons of a scanning tunneling
      microscope (STM), a statistical study of molecular switching reveals two specific
      locations of the molecule for which their efficiency is optimized. The CT
      mechanism is shown to propagate from two lateral aryl groups towards the
      porphyrin macrocycle inducing an intramolecular movement of two symmetric
      pyrroles. The measured switching efficiencies can thus be related to a Markus
      Jordner model to estimate relevant parameters that describe the dynamics of the
      CT process. Numerical simulations provide a precise description of the molecular
      conformations and unveil the molecular energy levels that are involved in the CT
      process. This quantitative method opens a completely original approach to study
      CT at the nanoscale.

PMID- 29063084
TI  - A simple culture system for long-term imaging of individual C. elegans.
AB  - We have miniaturized standard culture techniques to rear arrays of isolated,
      individual C. elegans throughout their lives on solid gel media. The resulting
      apparatus is compatible with brightfield and fluorescence microscopy, enabling
      longitudinal studies of morphology and fluorescent transgene expression. Our
      culture system exploits a novel crosslinking reaction between a polyethylene
      glycol hydrogel and a silicone elastomer to constrain animals to individual
      "corrals" on the gel surface. These devices are simple to construct on the
      benchtop with commercially available reagents, and, unlike microfluidic isolation
      methods, do not rely on micropatterned materials. We demonstrate that this new
      culture method has negligible effects on the physiology of C. elegans compared to
      standard culture on agar plates. In addition, RNAi techniques are effective in
      this system. Finally, the hydrogel-silicone binding chemistry that we developed
      also allows traditional microfluidic devices to be covalently attached to gel
      substrates instead of glass.

PMID- 29063086
TI  - Vanadium(v) oxoanions in basic water solution: a simple oxidative system for the
      one pot selective conversion of l-proline to pyrroline-2-carboxylate.
AB  - The unprecedented, direct chemical oxidation of l-proline to pyrroline-2
      carboxylate was achieved in water (pH 9-10) by means of NH4VO3/NH3 or V2O5/MOH (K
      = Na, K), and the anion was fully characterized as ammonium or alkaline metal
      salts. Quantitative yield and higher atom economy performance were achieved with
      the latter system, the alkaline salts being more stable than the ammonium one.
      Different mixed valence V(iv)/V(v) compounds precipitated from the reaction
      mixtures depending on the nature of the employed base. A possible reaction
      mechanism is proposed according to DFT calculations. The analogous reaction of
      trans-4-hydroxy-l-proline with NH4VO3/NH3 afforded pyrrole-2-carboxylic acid in
      81% yield, while sarcosine underwent prevalent decomposition under similar
      experimental conditions. Instead, no reaction was observed with primary (glycine,
      l-alanine, l-phenylalanine) and tertiary alpha-amino acids (N,N-dimethyl-l
      phenylalanine, N,N-dimethylglycine).

PMID- 29063087
TI  - Luminescent complexes made from chelating isocyanide ligands and earth-abundant
      metals.
AB  - In this invited frontier article, recently discovered d6 and d10 complexes with
      long-lived metal-to-ligand charge transfer (MLCT) excited states are highlighted.
      Chelating diisocyanide ligands give access to emissive Mo(0) and Cr(0) complexes
      with d6 electron configuration exhibiting photophysical properties similar to
      those of Ru(ii) polypyridines or cyclometalated Ir(iii) complexes. With Ni(0),
      these ligands yield luminescent tetrahedral d10 complexes similar to
      isoelectronic Cu(i) bis(diimine) compounds.

PMID- 29063088
TI  - A metabolite of nobiletin, 4'-demethylnobiletin and atorvastatin synergistically
      inhibits human colon cancer cell growth by inducing G0/G1 cell cycle arrest and
      apoptosis.
AB  - Combining different chemopreventive agents is a promising strategy to reduce
      cancer incidence and mortality due to potential synergistic interactions between
      these agents. Previously, we demonstrated that oral administration of nobiletin
      (NBT, a citrus flavonoid) at 0.05% (w/w, in diet) together with atorvastatin
      (ATST, a lipid-lowering drug) at 0.02% (w/w, in diet) produced much stronger
      inhibition against colon carcinogenesis in rats in comparison with that produced
      by NBT (at 0.1% w/w in diet) or ATST (at 0.04% w/w in diet) alone at higher
      doses. To further elucidate the mechanism of this promising synergy between NBT
      and ATST, herein, we measured the levels of NBT, its major metabolites and ATST
      in the colonic tissue of rats fed NBT (0.05% w/w, in diet) + ATST (0.02% w/w, in
      diet), and determined the mode of interaction between the major NBT metabolite
      and ATST in inhibiting colon cancer cell growth. HPLC-MS analysis showed that 4'
      demethylnobiletin (4DN) is the most abundant metabolite of NBT with a level about
      5-fold as high as that of NBT in the colonic tissue, which indicated the
      potential significance of 4DN in mediating the biological effects of NBT in the
      colon. We found that co-treatments of 4DN/ATST at 2 : 1 concentration ratio
      produced much stronger growth inhibitory effects on human colon cancer HT-29
      cells than 4DN or ATST alone, and isobologram analysis confirmed that this
      enhanced inhibitory effect by the 4DN/ATST combination was highly synergistic.
      The co-treatment of 4DN/ATST led to G0/G1 cell cycle arrest and induced extensive
      apoptosis in HT-29 cells. Furthermore, the 4DN/ATST co-treatment profoundly
      modulated key signaling proteins related to the regulation of the cell cycle and
      apoptosis. Our results demonstrated a strong synergy produced by the 4DN/ATST co
      treatment in inhibiting colon cancer cell growth, which provided a novel
      mechanism by which NBT/ATST in combination synergistically inhibit colon
      carcinogenesis.

PMID- 29063090
TI  - Amino acid/crown ether hybrid materials: how charge affects liquid crystalline
      self-assembly.
AB  - To probe the influence of electrostatic interactions on the mesomorphic self
      assembly and phase behaviour of hybrid liquid crystals a series of crown
      ether/tyrosine hybrid systems was prepared by Steglich esterification of alkyl N
      (tert-butoxycarbonyl)-l-tyrosinates with 4-carboxybenzo[15]crown-5 and 4
      carboxybenzo[18]crown-6. The obtained derivatives allowed further manipulations
      at the NH functional group and complexation of the crown ether unit with NaI to
      give neutral or charged hybrid materials. All compounds were investigated by
      differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and
      X-ray diffraction (XRD) measurements. Neither the variation of the N-protecting
      group, introduction of charge at the N-terminus nor anion exchange (Cl vs. I)
      resulted in mesomorphism. In contrast, N-Boc-protected and unprotected hybrids
      formed rectangular columnar (Colr) mesophases with phase widths up to 35 K. NaI
      complexation switched these neutral thermotropic derivatives into ionic liquid
      crystals (ILCs) and induced a change of mesophase type from Colr to smectic A
      (SmA). A comparison of experimentally obtained layer distances and theoretically
      calculated molecular lengths indicated bilayer SmA formation with interdigitated
      alkyl chains. Packing models for both mesophase types are proposed and discussed
      with respect to stabilizing interactions.

PMID- 29063089
TI  - The interaction of halogen atoms and molecules with borophene.
AB  - The realization of buckled monolayer sheets of boron (i.e., borophene) and its
      other polymorphs has attracted significant interest in the field of two
      dimensional systems. Motivated by borophene's tendency to donate electrons, we
      analyzed the interaction of single halogen atoms (F, Cl, Br, I) with borophene.
      The possible adsorption sites are tested and the top of the boron atom is found
      as the ground state configuration. The nature of bonding and strong chemical
      interaction is revealed by using projected density of states and charge
      difference analysis. The migration of single halogen atoms on the surface of
      borophene is analyzed and high diffusion barriers that decrease with atomic size
      are obtained. The metallicity of borophene is preserved upon adsorption but
      anisotropy in electrical conductivity is altered. The variation of adsorption and
      formation energy, interatomic distance, charge transfer, diffusion barriers, and
      bonding character with the type of halogen atom are explored and trends are
      revealed. Lastly, the adsorption of halogen molecules (F2, Cl2, Br2, I2),
      including the possibility of dissociation, is studied. The obtained results are
      not only substantial for fundamental understanding of halogenated derivatives of
      borophene, but also are useful for near future technological applications.

PMID- 29063091
TI  - A baseline drift detrending technique for fast scan cyclic voltammetry.
AB  - Fast scan cyclic voltammetry (FSCV) has been commonly used to measure
      extracellular neurotransmitter concentrations in the brain. Due to the unstable
      nature of the background currents inherent in FSCV measurements, analysis of FSCV
      data is limited to very short amounts of time using traditional background
      subtraction. In this paper, we propose the use of a zero-phase high pass filter
      (HPF) as the means to remove the background drift. Instead of the traditional
      method of low pass filtering across voltammograms to increase the signal to noise
      ratio, a HPF with a low cutoff frequency was applied to the temporal dataset at
      each voltage point to remove the background drift. As a result, the HPF utilizing
      cutoff frequencies between 0.001 Hz and 0.01 Hz could be effectively used to a
      set of FSCV data for removing the drifting patterns while preserving the temporal
      kinetics of the phasic dopamine response recorded in vivo. In addition, compared
      to a drift removal method using principal component analysis, this was found to
      be significantly more effective in reducing the drift (unpaired t-test p <
      0.0001, t = 10.88) when applied to data collected from Tris buffer over 24 hours
      although a drift removal method using principal component analysis also showed
      the effective background drift reduction. The HPF was also applied to 5 hours of
      FSCV in vivo data. Electrically evoked dopamine peaks, observed in the nucleus
      accumbens, were clearly visible even without background subtraction. This
      technique provides a new, simple, and yet robust, approach to analyse FSCV data
      with an unstable background.

PMID- 29063092
TI  - Carbon-sulphur cross coupling reactions catalyzed by nickel-based coordination
      polymers based on metalloligands.
AB  - This work illustrates two Ni2+ based coordination polymers (CPs, 1-Ni and 2-Ni)
      synthesized using two related Co3+ based metalloligands offering appended
      arylcarboxylate groups. The crystal structure of 1-Ni displays a porous 3D
      network having well-defined major and minor pores whereas 2-Ni exhibits a
      somewhat densely packed structure. Both CPs supported the exchange of coordinated
      water molecules and the inclusion of iodine within their porous structure whereas
      binding studies illustrated that the Ni(ii) ion in these CPs can bind thiophenol,
      a reagent used in the C-S cross coupling reactions. The two CPs functioned as the
      reusable heterogeneous catalysts for the C-S cross coupling reactions between
      substituted aromatic halides and thiophenol as well as cyclohexanethiol and
      ethanethiol.

PMID- 29063093
TI  - NMR window of molecular complexity showing homeostasis in superorganisms.
AB  - NMR offers tremendous advantages in the analyses of molecular complexity, such as
      crude bio-fluids, bio-extracts, and intact cells and tissues. Here we introduce
      recent applications of NMR approaches, as well as next generation sequencing
      (NGS), for the evaluation of human and environmental health (i.e., maintenance of
      a homeostatic state) based on metabolic and microbial profiling and data science.
      We describe useful databases and web tools that are used to support these studies
      by facilitating the characterization of metabolites from complex NMR spectra.
      Because the NMR spectra of metabolic mixtures can produce numerical matrix data
      (e.g., chemical shift versus intensity) with high reproducibility and inter
      institution convertibility, advanced data science approaches, such as
      multivariate analysis and machine learning, are desirable; therefore, we also
      introduce informatics techniques derived from heterogeneously measured data, such
      as environmental microbiota, for the extraction of submerged information using
      data science approaches. We summarize recent studies of microbiomes that are
      based on these techniques and show that, particularly in human studies, NMR-based
      metabolic characterization of non-invasive samples, such as feces, can provide a
      large quantity of beneficial information regarding human health and disease.

PMID- 29063094
TI  - Three-dimensional porous V2O5 hierarchical spheres as a battery-type electrode
      for a hybrid supercapacitor with excellent charge storage performance.
AB  - Three-dimensional porous V2O5 hierarchical spheres composed of stacked platelets
      were fabricated by a facile, low-cost and template-free method. The synthetic
      route involved precipitation of precursor microspheres in aqueous solution at
      room temperature and subsequent calcination. Various techniques including XRD, FE
      SEM, TEM, EDS, IR, Raman and nitrogen adsorption-desorption isotherms were used
      to reveal the composition, morphology and structure of the as-obtained porous
      V2O5 hierarchical spheres. The BET specific surface area of V2O5 hierarchical
      spheres measured 14 m2.g-1 and their average pore size reached 18.2 nm, and a
      majority of pores in the hierarchical structures were mesoporous. Electrochemical
      properties of the as-obtained three-dimensional porous V2O5 hierarchical spheres
      as a battery-type electrode were investigated by cyclic voltammetry (CV),
      galvanostatic charge-discharge (GCD) and electrochemical impedance spectroscopy
      (EIS). The hierarchical spheres displayed excellent rate capability and an
      excellent capacity up to 473 C.g-1 at 0.2 A.g-1 owing to their high ion transfer
      speed that transpired between electrolytes and active electrode materials. A
      flexible hybrid supercapacitor (HSC) device was fabricated using the as-obtained
      three-dimensional porous V2O5 hierarchical spheres as a cathode and activated
      carbon as an anode and delivered an excellent capacitance of 0.26 F cm-2 at 10 mV
      s-1. The good electrochemical performance of the porous V2O5 hierarchical spheres
      indicates their high potential as a battery-type electrode material for the HSC
      device.

PMID- 29063095
TI  - One step fabrication of mesh-reinforced hierarchic perforated microporous
      honeycomb films with tunable filtering property.
AB  - Highly ordered porous films whose pore size ranges from submicron to micron scale
      have always been an extensive area of research due to their broad range of
      application to photonic crystals, cell culturing scaffolds, filtration and
      separation membranes, just to name a few. However, the fragile nature of such a
      functional porous film has hindered its implementation to advanced uses. Inspired
      by the hierarchic structure in nature which offers both robustness and
      functionality, we created in a single fabrication step a mesh-reinforced
      hierarchic perforated honeycomb film with highly ordered micron pores using the
      breath figure method. By using the elastomer 1,2-polybutadiene as the material
      for the film in the combination of the mesh grid, the pore size of the obtained
      film can be tuned upon stretching. Tubular structures made from the mesh
      reinforced hierarchic perforated porous honeycomb film with tunable pore size
      have been demonstrated.

PMID- 29063096
TI  - Correction: automated and controlled mechanical stimulation and functional
      imaging in vivo in C. elegans.
AB  - Correction for 'Automated and controlled mechanical stimulation and functional
      imaging in vivo in C. elegans' by Yongmin Cho et al., Lab Chip, 2017, 17, 2609
      2618.

PMID- 29063097
TI  - Synthesis and derivatisation of ceric tris(tert-butoxy)siloxides.
AB  - Metathesis reactions involving cerium(iv) complexes are generally hampered by a
      high tendency for reduction to the favoured trivalent state and a preference for
      ligand redistribution. Heteroleptic ceric Ce[OSi(OtBu)3]3Cl(thf) is easily
      obtained from the oxidation of Ce[OSi(OtBu)3]3(thf)2 with trityl chloride, while
      the absence of thf triggers formation of homoleptic Ce[OSi(OtBu)3]4.
      Ce[OSi(OtBu)3]3Cl(thf) engages in salt metathesis reactions with the alkali metal
      alkoxides KOCH3 and KOtBu, forming Ce[OSi(OtBu)3]3(OR)(thf)x, but experiences an
      extensive reductive ligand redistribution with the methylating agent ZnMe2.

PMID- 29063098
TI  - Zirconium arene triple-decker sandwich complexes: synthesis, electronic structure
      and bonding.
AB  - Reduction of a permethylpentalene zirconium(iv) chloride complex [eta8-Pn*Zr(MU
      Cl)3/2]2(MU-Cl)2Li.THFx with KC8 in benzene results in activation of the aromatic
      solvent to yield an "inverted sandwich" complex, [eta8-Pn*Zr]2(MU-eta6:eta6-C6H6)
      (1). The reactions in toluene, cumene, o-xylene and m-xylene also yield analogous
      solvent activated triple-decker sandwich complexes, which have been structurally
      characterised by single-crystal X-ray diffraction. Edge energies in the Zr K-edge
      XANES spectra are not distinguishable between 1 and formally Zr(ii) and Zr(iv)
      reference compounds, suggesting a broad edge structure. DFT calculations best
      describe the bonding in 1 as highly covalent with frontier molecular orbitals
      showing almost equal contributions from benzene and the Zr-permethylpentalene
      fragments.

PMID- 29063099
TI  - High-nuclearity heterometallic clusters with both an anion and a cation
      sandwiched by planar cluster units: synthesis, structure and properties.
AB  - To develop high-nuclearity clusters as multi-functional materials, we prepared a
      new type of sandwich clusters using an anion-templated synthetic strategy. The
      reactions of (2R,3R)-2,3-dihydroxybutanedioylbis(salicylidene hydrazone) (H6L)
      with [Cu2(OAc)4(H2O)2] in the presence of alkali metal halide (NaCl, NaBr, KCl or
      KBr) provided four high-nuclearity clusters [MCu18L6X(C5H5N)15(DMF)3].3DMF.6H2O
      (M = Na and X = Cl (1); M = Na and X = Br (2); M = K and X = Cl (3); and M = K
      and X = Br (4)). They represent a new type of nanoscale high-nuclearity
      heterometallic sandwich clusters, in which the halide anion is fully sandwiched
      by two planar nonanuclear clusters, and the alkali metal ion is half-sandwiched
      on the top of the upper planar nonanuclear cluster. The experimental magnetic
      data and simulating results reveal dominant antiferromagnetic interactions
      between metal ions in these compounds. Their dielectric constants and electric
      hysteresis loops were also measured.

PMID- 29063100
TI  - Synthesis and reactivity of iron-dinitrogen complexes bearing anionic methyl- and
      phenyl-substituted pyrrole-based PNP-type pincer ligands toward catalytic
      nitrogen fixation.
AB  - Iron-dinitrogen complexes bearing methyl- and phenyl-substituted pyrrole-based
      anionic PNP-type pincer ligands are prepared and characterized by X-ray analysis.
      The former complex is found to work as a more effective catalyst than that
      bearing a non-substituted PNP-type pincer ligand toward the transformation of
      nitrogen gas into ammonia and hydrazine under mild reaction conditions.

PMID- 29063101
TI  - Visible light-promoted dihydroxylation of styrenes with water and dioxygen.
AB  - An efficient visible light promoted metal-free dihydroxylation of styrenes with
      water and dioxygen has been developed for the construction of vicinal alcohols.
      The protocol was operationally simple with a broad substrate scope. The
      mechanistic studies demonstrated that one of the hydroxyl groups came from water
      and the other one came from molecular oxygen. Additionally, the beta-alkyoxy
      alcohols could also be obtained using a similar strategy.

PMID- 29063102
TI  - Stress-related arterial hypertension in Gper-deficient rats.
AB  - Numerous studies have demonstrated that estrogens may exert multifaceted effects
      on the cardiovascular system via activating the classical nuclear receptors
      ERalpha or ERbeta and the novel G protein coupled estrogen receptor (Gper).
      However, some studies have reported inconsistent cardiovascular phenotypes in
      Gper-deficient mice. The current study was aimed to reveal the effects of genetic
      deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats.
      Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9
      gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n
      = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6
      males) were measured under awake and restrained conditions through the non
      invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT
      rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5
      to 9, indicative of stress-related sympathoexcitation in the first few days and
      gradual adaptation to the restrained stress in later days. Gper-deficient rats
      had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to
      day 3) and similar ABP in later days of measurement compared with the WT rats.
      The heart rate of male Gper-deficient rats was consistently higher than that of
      the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats
      appeared to show slower body weight gain than the WT counterparts during the
      study period. Under anesthesia, ABP of Gper-deficient rats was not significantly
      different from their WT counterparts. These results indicate that Gper-deficient
      rats may be more sensitive to stress-induced sympathoexcitation and highlight the
      importance of Gper in the regulation of the cardiovascular function in stressful
      conditions.

PMID- 29063103
TI  - Influence of insulin on growth hormone secretion, level and growth hormone
      signalling.
AB  - Growth hormone (GH), as a vital hormone, has to experience a series of processes
      to fulfill its function including secretion, entering the circulation to reach
      target tissues (pre-receptor process), binding on the GH receptor (GHR) and
      triggering signaling inside cells (post-GHR process). Insulin can directly or
      indirectly influence part of these processes. GH secretion from pituitary
      somatotropes is regulated by GH-releasing hormone (GHRH) and somatostatin (SS)
      from hypothalamus. Insulin may exert positive or negative effects on the neurons
      expressing GHRH and SS and somatotropes under healthy and pathological conditions
      including obesity and diabetes. Glucose and lipid levels in circulation and
      dietary habits may influence the effect of insulin on GH secretion. Insulin may
      also affect GHR sensitivity and the level of insulin-like growth factor 1 (IGF
      1), thus influence the level of GH. The GH signaling is also important for GH to
      play its role. GH signaling involves GHR/JAK2/STATs, GHR/JAK2/SHC/MAPK and
      GH/insulin receptor substrate (IRS)/PI3K/Akt pathways. These pathways may be
      shared by insulin, which is the basis for the interaction between insulin and GH,
      and insulin may attenuate or facilitate the GH signal by influencing molecules in
      the pathways. Many factors are related to the effect of insulin, among them the
      most important ones are duration of action and amount of insulin. The tendency of
      insulin-reduced GH signaling becomes obvious with increased dose and acting time
      of insulin. The participation of suppressor of cytokine signaling (SOCS), the
      interaction between JAK2 and IRS, and GHR sensitivity should also be considered
      when discovering GH signal. The involvement of SS in response to insulin is not
      clear yet. The details of how GH secretion, level and signaling change in
      response to time and dose of insulin treatment warrant further studies.

PMID- 29063104
TI  - [Regulation of vascular function by nitric oxide-related S-nitrosylation].
AB  - Nitric oxide (NO), well known as the endothelium-derived relaxing factor (EDRF),
      has become increasingly recognized as an important determinant of cardiovascular
      diseases. A molecular pathway by which NO accomplishes various biochemical
      processes is the cGMP-independent post-translational modification of protein, S
      nitrosylation. Here we review the biochemistry and regulating mechanisms of NO
      related S-nitrosylation of proteins, and discuss the multiple roles of S
      nitrosylation in vascular functions and pathology in particular.

PMID- 29063105
TI  - The roles of microRNA-22 in myocardial infarction.
AB  - Myocardial infarction (MI) is the leading cause of morbidity and mortality
      worldwide. The regeneration capacity of the adult mammalian heart is very
      limited, so that the lost cells are replaced by fibrotic scar. This is followed
      by remodeling of the surrounding myocardium, which includes cardiac hypertrophy
      and fibrosis, and makes the ventricular wall thicken and stiffen. This adverse
      cardiac remodeling leads to impaired cardiac function and eventually leads to
      heart failure. Extensive studies have revealed that microRNAs (miRNAs) play an
      essential role in cardiovascular diseases. microRNA-22 (miR-22) is one of the
      most abundant miRNA in the heart. Many studies have demonstrated that miR-22
      plays critical roles in MI and subsequent cardiac remodeling. In this review, we
      summarized the recent research progresses, including the regulatory effects of
      miR-22 in oxidative stress, cardiac apoptosis, autophagy, hypertrophy, fibrosis
      and regeneration.

PMID- 29063106
TI  - [Recent progress of mitochondrial quality control in ischemic heart disease and
      its role in cardio-protection of vagal nerve].
AB  - Ischemic heart disease (IHD) is the life-threatening cardiovascular disease.
      Mitochondria have emerged as key participants and regulators of cellular energy
      demands and signal transduction. Mitochondrial quality is controlled by a number
      of coordinated mechanisms including mitochondrial fission, fusion and mitophagy,
      which plays an important role in maintaining healthy mitochondria and cardiac
      function. Recently, dysfunction of each process in mitochondrial quality control
      has been observed in the ischemic hearts. This review describes the mechanism of
      mitochondrial dynamics and mitophagy as well as its performance linked to
      myocardial ischemia. Moreover, in combination with our study, we will discuss the
      effect of vagal nerve on mitochondria in cardio-protection.

PMID- 29063108
TI  - Regulation of iron metabolism by hypoxia-inducible factors.
AB  - Hypoxia-inducible factors (HIFs) are central mediators of cellular adaption to
      hypoxia. The heterodimeric HIF transcription factors consist of HIF-alpha and HIF
      beta, that form functional HIFs. Mammals contain HIF-1alpha, HIF-2alpha, and HIF
      3alpha. HIFs play a key role in iron metabolism by regulating the expression of
      iron-related proteins, such as divalent metal transporter 1 (DMT1), ferroportin 1
      (FPN1), duodenal cytochrome b (Dcytb), and transferrin receptor (TfR). Hepcidin
      and iron regulatory proteins (IRPs), the central mediators for systematic and
      intracellular iron homeostasis, are also regulated by HIFs. In this review, we
      summarized the regulatory effects of HIFs on iron-related proteins, thus
      providing insights into the control of HIFs as therapeutic strategies for some
      iron related disorders.

PMID- 29063107
TI  - Evidence-based blood pressure reducing actions of electroacupuncture: mechanisms
      and clinical application.
AB  - Hypertension is a serious world-wide health problem as it increases
      cardiovascular atherosclerotic risk, stroke and attending morbidity and
      mortality. Both systolic and diastolic blood pressures and particularly systolic
      pressure increase with aging. The downsides from pharmacological therapy have led
      to consideration of additional treatments, including acupuncture, which evokes
      endogenous neural-hormonal systems to lower blood pressure. Using basic science
      studies to guide clinical approaches to research, it is apparent that low
      frequency, low intensity electroacupuncture reduces sympathetic outflow in
      approximately 70% of patients with mild to moderate hypertension who are off
      antihypertensive drugs. Systolic and, to a lesser extent, diastolic arterial
      blood pressures can be lowered over two to four weeks for prolonged periods,
      lasting as long as one month, after cessation of an eight weeks of once weekly
      stimulation. Many questions about long-term therapy, treatment of resistant
      patients and efficacy in patients on medication remain to be studied. Current
      data, however, suggest that there may be a role of acupuncture in treatment of
      hypertension.

PMID- 29063109
TI  - [Subthalamic nucleus: from circuits, functions to a deep brain stimulation target
      for the treatment of Parkinson's disease].
AB  - The subthalamic nucleus (STN) is the only excitatory glutamatergic nucleus in the
      basal ganglia circuitry. It not only is a key node in the classical indirect
      pathway, but also forms the "hyperdirect" pathway directly connecting the cortex,
      and even is implicated as a pacemaker for activity of whole basal ganglia. Due to
      the key position of STN in the basal ganglia circuitry, the STN is an optimal
      target for deep brain stimulation (DBS) in the neurosurgical treatment of
      Parkinson's disease (PD). However, the therapeutic mechanisms underlying the
      amelioration of parkinsonian motor dysfunctions induced by DBS on STN remain
      enigmatic. This paper reviews recent progresses in the studies on the input
      output configurations and functions of STN in the basal ganglia circuitry, and
      summarizes the hypotheses for mechanisms of DBS for the treatment of motor
      dysfunctions in PD. Studying on the DBS mechanisms will not only help to develop
      strategies for treatment of PD, but also contribute to the understanding of
      functions of the basal ganglia circuitry.

PMID- 29063110
TI  - [The structure and function of habenula].
AB  - The habenula (Hb) is an evolutionarily conserved diencephalic structure in
      vertebrates. It is considered as an emotion center and plays critical roles in
      regulating diverse types of emotion-related behaviors, including anxiety, fear,
      reward, depression, and nicotine withdrawal. On the one hand, action selection-
      and emotion-relevant inputs are transferred to the Hb through the basal ganglia
      and limbic system, respectively. At the same time, sensory inputs of multiple
      modalities also converge on the Hb. Among them, the visual input of the Hb from
      the retina ganglion cells - thalamus pathway has been found to play a critical
      role in light-preference behavior of zebrafish. On the other hand, the Hb
      projects to two main neuromodulatory systems, the dopaminergic system and the
      serotoninergic system. As the Hb receives both internal emotion inputs and
      external sensory inputs and regulates the function of neuromodulatory systems,
      its functions are quite diverse and complex. In this review, we summarize the
      progress in both the structure and connection of the Hb and propose future study
      direction.

PMID- 29063111
TI  - [Molecular mechanisms of NMDA receptor-MAPK-CREB pathway underlying the
      involvement of the anterior cingulate cortex in pain-related aversion].
AB  - The pain experience includes a sensory-discriminative component and an emotional
      affective component. The great progress in the genetic, molecular, cellular and
      systemic levels on the study of the sensory dimension of pain has been made.
      However, the study of the emotional components of pain is relatively backward. A
      line of clinic observations indicates that chronic pain and pain-related negative
      emotion affect the physical and mental health of patients. This review summarizes
      the main progress from our and other laboratories regarding the affective
      component of pain, elaborates the neuronal mechanisms of pain-related aversive
      emotion in the anterior cingulate cortex (ACC), especially the critical role of
      NMDA receptors and ERK-CREB pathway. A variety of regulatory molecules, such as
      synapse associated protein SIP30 and estrogen contribute to pain-related aversive
      emotion via facilitating presynaptic glutamate release and postsynaptic NMDA
      receptor-mediated synaptic transmission. The far-reaching effects of pain-related
      negative emotion on patients with chronic pain are emphasized.

PMID- 29063112
TI  - [The mechanism and function of hippocampal neural oscillation].
AB  - Neural oscillation is rhythmic or repetitive neural activity in the central
      nervous system that is usually generated by oscillatory activity of neuronal
      ensembles, reflecting regular and synchronized activities within these cell
      populations. According to several oscillatory bands covering frequencies from
      approximately 0.5 Hz to >100 Hz, neural oscillations are usually classified as
      delta oscillation (0.5-3 Hz), theta oscillation (4-12 Hz), beta oscillation (12
      30 Hz), gamma oscillation (30-100 Hz) and sharp-wave ripples (>100 Hz ripples
      superimposed on 0.01-3 Hz sharp waves). Neural oscillation in different
      frequencies can be detected in different brain regions of human and animal during
      perception, motion and sleep, and plays an essential role in cognition, learning
      and memory process. In this review, we summarize recent findings on neural
      oscillations in hippocampus, as well as the mechanism and function of hippocampal
      theta oscillation, gamma oscillation and sharp-wave ripples. This review may
      yield new insights into the functions of neural oscillation in general.

PMID- 29063114
TI  - [Research progress of complement-C1q/tumor necrosis factor-related protein 3].
AB  - Complement-C1q/tumor necrosis factor-related protein 3 (CTRP3) is an adipokine
      that primarily identified in 2003 and is an important member of CTRP family.
      CTRP3 is expressed in various tissues and cell types, and is highly conserved
      among different species. Multiple novel functions of CTRP3 have been reported
      recently as the further research on this protein develops. CTRP3 not only affects
      the proliferation of chondrocytes and the pathogenesis of osteoarthritis, but
      also regulates multiple physiological and pathological processes including the
      secretion of testosterone and adipokines, glucose and lipid metabolism,
      mitochondrial biogenesis, inflammatory response, cell apoptosis, angiogenesis,
      vascular calcification and ventricular remodeling. The present review mainly
      focuses on the research progresses on CTRP3, including its discovery, gene and
      protein structure, expression regulation, and biological functions. The
      progresses summarized may provide new clues for the further investigation of
      CTRP3.

PMID- 29063115
TI  - [TRPV1: an important molecule involved in the peripheral sensitization during
      chronic pain and central pain modulation].
AB  - As chronic pain is a severe problem in clinics, study of the mechanisms of
      chronic pain and development of novel analgesic agents is of significance. In the
      past decade, our lab completed a series of studies on the regulatory mechanisms
      of functional sensitization and membrane trafficking of transient receptor
      potential vanilloid type 1 (TRPV1), a key molecule involved in the development of
      peripheral sensitization. Our studies elucidated the important regulatory roles
      of several protein kinases, including PKD1 (protein kinase D1), Cdk5 (cyclin
      dependent kinase 5) and LIMK (LIM-motif containing kinase), in inflammatory
      thermal hyperalgesia. Moreover, based on these findings, we constructed a series
      of transmembrane Tat-fusion peptides for pain relief. The potential role of
      central TRPV1 was discussed as well. Prelimbic subregion of prefrontal cortex was
      revealed to be a critical brain region involved in the interaction between pain
      sensation and pain emotions by our recent studies. In addition, our work
      attempted to improve the analgesic effects of the agents targeting TRPV1 and
      concurrently reduce their side effects. Herein we summarized the work of our lab
      in pain and pain modulation during the past decade.

PMID- 29063116
TI  - [Cannabinoid receptor system regulates ion channels and synaptic transmission in
      retinal cells].
AB  - Endocannabinoid receptor system is extensively expressed in the vertebrate
      retina. There are two types of cannabinoid receptors, CB1 and CB2. Activation of
      these two receptors by endocannabinoids N-arachidonoylethanolamide (anandamine,
      AEA) and 2-arachidonyl glycerol (2-AG) regulates multiple neuronal and glial ion
      channels, thus getting involved in retinal visual information processing. In this
      review, incorporating our results, we discuss the modulation of cannabinoid CB1
      and CB2 receptors on retinal neuronal and glial ion channels and retinal synaptic
      transmission.

PMID- 29063117
TI  - [Progress in multisensory integration during self motion processing].
AB  - In the daily life, we perceive the world around us by integrating multiple
      sensory cues (visual, auditory, olfactory, gustatory, tactile, vestibular and
      proprioceptive) to create a coherent, reliable representation that allows us to
      interact meaningfully with the environment. The integration of different sensory
      information is necessary for our perception, motor transformation, decision
      making, learning and memory. In the past decades, many interdisciplinary
      researchers have been attracted to the field of multisensory research, and
      tremendous advances have been made in this field. We review the researches on
      multisensory integration during self-motion perception in the past decades from
      the candidate areas, the integration principles and the neural correlation of the
      behaviors, with the intention to provide a comprehensive source for those
      interested in understanding the neural substrates for multisensory integration.
      Meanwhile, we also provide a prospect for the future research in this field.

PMID- 29063113
TI  - Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons.
AB  - Several non-receptor tyrosine kinase (nRTK) members are expressed in neurons of
      mammalian brains. Among these neuron-enriched nRTKs, two Src family kinase
      members (Src and Fyn) are particularly abundant at synaptic sites and have been
      most extensively studied for their roles in the regulation of synaptic activity
      and plasticity. Increasing evidence shows that the synaptic subpool of nRTKs
      interacts with a number of local substrates, including glutamate receptors (both
      ionotropic and metabotropic glutamate receptors), postsynaptic scaffold proteins,
      presynaptic proteins, and synapse-enriched enzymes. By phosphorylating specific
      tyrosine residues in the intracellular domains of these synaptic proteins either
      constitutively or in an activity-dependent manner, nRTKs regulate these
      substrates in trafficking, surface expression, and function. Given the high
      sensitivity of nRTKs to changing synaptic input, nRTKs are considered to act as a
      critical regulator in the determination of the strength and efficacy of synaptic
      transmission.

PMID- 29063118
TI  - [DREAM: a multifunctional transcriptional regulator].
AB  - DREAM (downstream regulatory element antagonist modulator), Calsenilin and KChIP3
      (potassium channel interacting protein 3) belong to the neuronal calcium sensor
      (NCS) superfamily, which transduces the intracellular calcium signaling into a
      variety of activities. They are encoded by the same gene locus, but have distinct
      subcellular locations. DREAM was first found to interact with DRE (downstream
      regulatory element) site in the vicinity of the promoter of prodynorphin gene to
      suppress gene transcription. Calcium can disassemble this interaction by binding
      reversibly to DREAM protein on its four EF-hand motifs. Apart from having calcium
      dependent DRE site binding, DREAM can also interact with other transcription
      factors, such as cAMP responsive element binding protein (CREB), CREB-binding
      protein (CBP) and cAMP responsive element modulator (CREM), by this concerted
      actions, DREAM extends the gene pool under its control. DREAM is predominantly
      expressed in central nervous system with its highest level in cerebellum, and
      accumulating evidence demonstrated that DREAM might play important roles in pain
      sensitivity. Novel findings have shown that DREAM is also involved in learning
      and memory processes, Alzheimer's disease and stroke. This mini-review provides a
      brief introduction of its discovery history and protein structure properties,
      focusing on the mechanism of DREAM nuclear translocation and gene transcription
      regulation functions.

PMID- 29063119
TI  - [Inflammatory mechanism of depression and its new strategy for diagnosis and
      treatment].
AB  - Depression is a major class of mental illness; owing to its high prevalence, high
      disability rate and heavy disease burden, it has become a stern and formidable
      global health problem. It is generally believed that the etiology of depression
      is multifactorial, which is related to gender differences, chronic stress,
      dietary behavior and drug abuse. At present, the exact pathophysiological
      mechanism of depression still remains unclear, but researchers across the globe
      put forward various hypotheses to interpret the possible access to this disease,
      including monoamine neurotransmitter disturbance, hypothalamic-pituitary-adrenal
      (HPA) axis dysfunction, lack of neurotrophic factors and excessive pro
      inflammatory cytokines. Based on the latest research evidence and the objective
      fact that traditional antidepressants may be ineffective in some particular
      patients, the "cytokine theory" tends to attract more and more attention
      recently. To date, researches on the role of cytokines in the pathogenesis of
      depression mainly focus on pro-inflammatory cytokines, especially categories
      including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)
      and interleukin-6 (IL-6). With the proceeding of researches from all over the
      world, a variety of novel molecules and mechanisms were postulated. This paper
      summarized a large amount of in vitro and in vivo research evidence, in order to
      review the current progress of the researches on pathophysiology of depression
      from the perspective of pro-inflammatory cytokines. Since the response rate of
      antidepressant therapy during present medical practice is unsatisfying, we
      suggest a new feasible diagnosis and treatment strategy, that is to distinguish
      the inflammatory status of patients with depression and take anti-inflammatory
      treatment into consideration. Totally, this novel strategy aims at modulating the
      conventional clinical protocol for treatment-resistant depressive patients and
      overcoming the limitation of insufficient antidepressant response possibly
      resulted from inflammation.

PMID- 29063120
TI  - [Advances in mechanism of autophagy in renal tubular injury].
AB  - Autophagy is a lysosome-dependent degradation process that eliminates damaged
      macromolecular proteins and aging organelles to maintain intracellular
      homeostasis. Autophagy is observed in almost all eukaryotic cells and plays
      important roles in many cellular physiological processes, including the cell
      proliferation and growth, cellular functional alteration and phenotypical
      transition. Renal tubule is an important target for renal injury under different
      pathological conditions. Following the discoveries of the molecular basis of
      autophagy, accumulated lines of evidence have indicated that autophagy
      dysfunction in tubule is involved in the pathogenesis of many renal diseases.
      This review will summarize the recent progress in molecule mechanism of autophagy
      and its roles in renal tubular injury.

PMID- 29063121
TI  - [The platelet-producing function of lung].
AB  - It is generally believed that platelets are cytoplasmic bodies with biological
      activity falling off the cytoplasm of megakaryocytes from bone marrow. However, a
      large number of megakaryocytes have been found in the lung tissue in many
      researches. Whether the lung has the function of producing platelets has been
      controversial. In this paper, we briefly review the proposition, early stage
      researches, the latest confirmations and possible meaning of the hypothesis of
      platelet-producing function of lung.

PMID- 29063122
TI  - The education gradient in cancer screening participation: a consistent phenomenon
      across Europe?
AB  - OBJECTIVES: To extend the literature on educational inequalities in cancer
      screening participation (1) by simultaneously focusing on participation in
      screening for cervical, breast and colorectal cancer across 27 European countries
      and (2) by statistically testing whether these educational inequalities vary
      according to country-specific screening strategies: organised or opportunistic.
      METHODS: Self-reported data from Eurobarometer 66.2 (2006) on cancer screening
      participation in the preceding 12 months were used to outline cross-national
      variations in screening strategies, target populations and participation rates.
      Multilevel logistic regressions were applied. RESULTS: Individuals with higher
      levels of education were more likely to participate in screening for cervical,
      breast and colorectal cancer than were those with less education. Educational
      inequalities were significantly smaller in countries with organised cervical
      cancer screening than they were in countries with opportunistic screening (OR =
      0.716, 95% CI 0.549-0.935). The same interaction was observed for participation
      in screening for breast and colorectal cancer, albeit with marginal significance.
      CONCLUSIONS: This study clearly highlights the crucial role of educational level
      in the likelihood of participating in cancer screening. Countries can reduce
      educational inequalities by applying organised screening programmes.

PMID- 29063123
TI  - Cadherin 22 participates in the self-renewal of mouse female germ line stem cells
      via interaction with JAK2 and beta-catenin.
AB  - The self-renewal capacity of the stem cell pool determines tissue function and
      health. Cadherin-22 (Cdh22), a member of the cadherin superfamily, has two
      splicing patterns in rats, and the short type that lacks a catenin binding domain
      is closely related to spermatogonial stem cell self-renewal. Previously, we
      reported that CDH22 was highly expressed in mouse ovary germ cells, especially in
      female germ line stem cells (FGSCs). However, its underlying function in FGSCs is
      still not clear. Here, we found that Cdh22 encodes only one type of protein
      product in mice and demonstrated that CDH22 was required for FGSC self-renewal.
      In addition, JAK2 and beta-catenin were found to interact with CDH22 and be
      involved in CDH22 signaling in mouse FGSCs. Moreover, extrinsic CDH22 was
      identified as a potential molecule that participates in FGSC adhesion and is
      pivotal for FGSC maintenance and self-renewal. These results reveal that CDH22
      functions as an essential molecule in FGSC maintenance and self-renewal via
      different mechanisms, including interaction with the JAK-STAT signaling pathway
      and beta-catenin.

PMID- 29063124
TI  - [Diagnostic importance of the PR segment when interpreting the ECG].

PMID- 29063125
TI  - [Structured bedside-ultrasound in intensive care medicine].
AB  - The so-called point-of-care ultrasound (POCUS) is of increasing importance for
      diagnostics and therapy control in intensive care medicine. Based on focused
      thorax sonography, echocardiography, and abdominal sonography, the most important
      working and differential diagnoses can be demonstrated or excluded depending on
      the leading symptom. Sonographic-based algorithms allow a structured evaluation
      especially of patients with the common leading symptoms dyspnea and thoracic
      pain.

PMID- 29063127
TI  - Correction to: Islet-intrinsic effects of CFTR mutation.
AB  - Unfortunately, due to a tagging error, Dr Fiona N. Manderson Koivula's name is
      shown incorrectly as Koivula FN on PubMed. Her name appears correctly in the html
      and pdf versions of the paper.

PMID- 29063126
TI  - The antibody loci of the domestic goat (Capra hircus).
AB  - The domestic goat (Capra hircus) is an important ruminant species both as a
      source of antibody-based reagents for research and biomedical applications and as
      an economically important animal for agriculture, particularly for developing
      nations that maintain most of the global goat population. Characterization of the
      loci encoding the goat immune repertoire would be highly beneficial for both
      vaccine and immune reagent development. However, in goat and other species whose
      reference genomes were generated using short-read sequencing technologies, the
      immune loci are poorly assembled as a result of their repetitive nature. Our
      recent construction of a long-read goat genome assembly (ARS1) has facilitated
      characterization of all three antibody loci with high confidence and comparative
      analysis to cattle. We observed broad similarity of goat and cattle antibody
      encoding loci but with notable differences that likely influence formation of the
      functional antibody repertoire. The goat heavy-chain locus is restricted to only
      four functional and nearly identical IGHV genes, in contrast to the ten observed
      in cattle. Repertoire analysis indicates that light-chain usage is more balanced
      in goats, with greater representation of kappa light chains (~ 20-30%) compared
      to that in cattle (~ 5%). The present study represents the first characterization
      of the goat antibody loci and will help inform future investigations of their
      antibody responses to disease and vaccination.

PMID- 29063129
TI  - Accumulation of Methylmercury in Invertebrates and Masked Shrews (Sorex cinereus)
      at an Upland Forest-Peatland Interface in Northern Minnesota, USA.
AB  - Mercury (Hg) methylation is often elevated at the terrestrial-peatland interface,
      but methylmercury (MeHg) production at this "hot spot" has not been linked with
      in situ biotic accumulation. We examined total Hg and MeHg levels in peat,
      invertebrates and tissues of the insectivore Sorex cinereus (masked shrew),
      inhabiting a terrestrial-peatland ecotone in northern Minnesota, USA. Mean MeHg
      concentrations in S. cinereus (71 ng g-1) fell between concentrations measured in
      spiders (mean 70-140 ng g-1), and ground beetles and millipedes (mean 29-42 ng g
      1). Methylmercury concentrations in S. cinereus increased with age and differed
      among tissues, with highest concentrations in kidneys and muscle, followed by
      liver and brain. Nearly all Hg in S. cinereus was in the methylated form.
      Overall, the high proportional accumulation of MeHg in peat at the site (3.5%
      total Hg as MeHg) did not lead to particularly elevated concentrations in
      invertebrates or shrews, which are below values considered a toxicological risk.

PMID- 29063128
TI  - Aortic stiffness and ambulatory blood pressure as predictors of diabetic kidney
      disease: a competing risks analysis from the Rio de Janeiro Type 2 Diabetes
      Cohort Study.
AB  - AIMS/HYPOTHESIS: Diabetic kidney disease (DKD) is a microvascular complication
      associated with poor control of blood glucose and BP. We aimed to evaluate the
      predictors of development and progression of DKD in a cohort of high-risk
      individuals with type 2 diabetes, placing emphasis on ambulatory BP and arterial
      stiffness. METHODS: In a prospective study, 629 individuals without advanced
      renal failure had their renal function evaluated annually over a median follow-up
      period of 7.8 years. Ambulatory BP was monitored and aortic stiffness was
      assessed by carotid-femoral pulse wave velocity at baseline. Multivariate
      competing risks analysis with all-cause mortality, using the Fine and Gray
      approach, was used to examine the independent predictors of development and
      progression of DKD, a composite of development or progression of abnormal
      albuminuria and worsening of renal function (doubling of serum creatinine or
      progression to end-stage renal disease). RESULTS: At baseline, 197 individuals
      had DKD. During follow-up, DKD developed or progressed in 195 individuals,
      abnormal albuminuria developed or progressed in 125 individuals and renal
      function deteriorated in 91. After adjustments for baseline albuminuria and renal
      function, age, sex, diabetes duration and use of renin-angiotensin antagonists,
      poorer control of blood glucose (HR 1.17; 95% CI 0.98, 1.40; p = 0.09 for each 1
      SD increment in mean first-year HbA1c), higher ambulatory systolic BP (HR 1.28;
      95% CI 1.09, 1.50; p = 0.003, for each 1 SD increase in daytime systolic BP
      [SBP]) and increased aortic stiffness (HR 1.16; 95% CI 1.00, 1.34; p = 0.05) were
      independent predictors of development or progression of DKD. At baseline,
      ambulatory BP was a stronger predictor than BP measured in the clinic. Aortic
      stiffness predicted abnormal albuminuria development or progression (HR 1.26; 95%
      CI 1.02, 1.56; p = 0.036) whereas ambulatory BP was a stronger predictor of renal
      function deterioration (HR 1.32; 95% CI 1.09, 1.60; p = 0.005 for daytime SBP).
      CONCLUSIONS/INTERPRETATION: Poor blood glucose and BP control and increased
      aortic stiffness were the main predictors of development or progression of DKD;
      ambulatory SBP was a better predictor than BP measured in the clinic. Ambulatory
      BP monitoring and assessment of aortic stiffness should be more widely used in
      clinical type 2 diabetes management.

PMID- 29063130
TI  - What's new in the long-term neurodevelopmental outcome of critically ill
      children.

PMID- 29063131
TI  - ICM focus on thrombosis and bleeding.

PMID- 29063133
TI  - Split-bolus pancreas CTA protocol for local staging of pancreatic cancer and
      detection and characterization of liver lesions.
AB  - PURPOSE: To validate the use of a split-bolus pancreas CTA protocol for local
      staging of pancreatic cancer and to evaluate its ability to detect and
      characterize liver lesions. METHODS: Consecutive patients with pancreatic cancer
      who underwent split-bolus pancreas CTA between 12/2015 and 12/2016 were included
      in this IRB-approved HIPAA-compliant retrospective study. Objective evaluation of
      the abdominal vessels, the pancreas, the liver, and lesions, if present, was
      performed with attenuation measurements and tumor conspicuity and contrast-to
      noise ratio (CNR) calculations. An abdominal radiologist with 20 years of
      experience performed subjective evaluation of image quality and blindly detected
      and characterized liver lesions. Any inconclusive findings or grading scores were
      evaluated in consensus with another abdominal radiologist with 7 years of
      experience. Liver findings were validated using a composite reference standard to
      assess accuracy. RESULTS: There were 82 pancreatic cancer patients with a total
      of 91 liver findings. Tumor conspicuity and CNR were 60.8 +/- 35.1 HU and 8.0 +/-
      5.8 for the pancreatic lesions and 58 +/- 34.7 HU and 9.7 +/- 6.3 for the liver
      lesions, respectively. The accuracy, sensitivity, and specificity of the split
      bolus protocol for the hepatic findings were correspondingly 89/91 (97.8%, 95% CI
      92.3-99.4), 58/60 (96.7%, 95% CI 88.6-99.1), and 33/33 (100%, 95% CI 89.6-100).
      The subjective image quality ratings were optimal in more than 89% of the cases
      for various structures, with no non-diagnostic ratings. CONCLUSION: Split-bolus
      pancreas CTA protocol allows for detection and staging of pancreatic cancer, both
      for the primary tumor and detection and characterization of liver lesions.

PMID- 29063132
TI  - Tardus parvus waveforms in Doppler ultrasonography for hepatic artery stenosis
      after liver transplantation: can a new cut-off value guide the next step?
AB  - PURPOSE: Considering the high false-positive diagnosis of the tardus parvus
      waveform (TPW) in Doppler ultrasonography (DUS) for hepatic artery stenosis (HAS)
      after liver transplantation (LT), this study aimed to determine clinical features
      and new cut-off values to help guide treatment. MATERIALS AND METHODS: This
      retrospective study was approved by an Institutional Review Board. A total of 171
      LT recipients were included and underwent DUS and either computed tomography
      angiography or digital subtraction angiography with an interval < 4 weeks at
      least 1 month post-LT. The DUS of 69 patients exhibited TPW [defined as resistive
      index (RI) < 0.5 and systolic acceleration time (SAT) > 0.08 s]. A multilevel
      likelihood ratio (LR) analysis was used to explore new cut-off values for DUS. In
      addition, abnormal liver function was considered additional evidence (defined as
      any liver enzyme > 3-fold of the upper limit of normal level or 2-fold
      increased). The results were stratified into three categories, category 1
      (subjects with traditional TPW), category 2 (subjects with traditional TPW and
      abnormal liver function), and category 3 (subjects with traditional TPW and
      abnormal liver function, or with new cut-off values), and the diagnostic
      performance of each category was analyzed. RESULTS: The LR analysis revealed new
      cut-off values of RI < 0.4 (LR = 10.58) or SAT > 0.12 s (LR = 16.46). The false
      positive rates for categories 2 and 3 were significantly lower (7.6% vs. 18.1%, P
      = 0.038; 1.9% vs. 18.1%, P < 0.001, respectively) than those for category 1,
      while the sensitivity for category 2 was significantly lower (41.8% vs. 74.6%, P
      < 0.001; 41.8% vs. 61.2%, P = 0.038, respectively) than that for categories 1 and
      3. CONCLUSION: Using either (1) RI < 0.4 or SAT > 0.12 s, or (2) traditional TPW
      (RI < 0.5 and SAT > 0.08 s) in the presence of abnormal liver functions as the
      DUS criteria for HAS will significantly decrease the false-positive rate compared
      to traditional TPW without a significant increase in the false-negative rate.

PMID- 29063134
TI  - PFOS induces proliferation, cell-cycle progression, and malignant phenotype in
      human breast epithelial cells.
AB  - Perfluorooctanesulfonic acid (PFOS) is a synthetic fluorosurfactant widely used
      in the industry and a prominent environmental toxicant. PFOS is persistent,
      bioaccumulative, and toxic to mammalian species. Growing evidence suggests that
      PFOS has the potential to interfere with estrogen homeostasis, posing a risk of
      endocrine-disrupting effects. Recently, concerns about a potential link between
      PFOS and breast cancer have been raised, but the mechanisms underlying its
      actions as a potential carcinogen are unknown. By utilizing cell proliferation
      assays, flow cytometry, immunocytochemistry, and cell migration/invasion assays,
      we examined the potentially tumorigenic activity of PFOS (100 nM-1 mM) in MCF-10A
      breast cell line. The results showed that the growth of MCF-10A cells exposed to
      1 and 10 uM PFOS was higher compared to that of the control. Mechanistic studies
      using 10 uM PFOS demonstrated that the compound promotes MCF-10A proliferation
      through accelerating G0/G1-to-S phase transition of the cell cycle after 24, 48,
      and 72 h of treatment. In addition, PFOS exposure increased CDK4 and decreased
      p27, p21, and p53 levels in the cells. Importantly, treatment with 10 uM PFOS for
      72 h also stimulated MCF-10A cell migration and invasion, illustrating its
      capability to induce neoplastic transformation of human breast epithelial cells.
      Our experimental results suggest that exposure to low levels of PFOS might be a
      potential risk factor in human breast cancer initiation and development.

PMID- 29063135
TI  - Metal chelators and neurotoxicity: lead, mercury, and arsenic.
AB  - This article reviews the clinical use of the metal chelators sodium 2,3
      dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA),
      and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and
      poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has
      considerably lower toxicity than the classic heavy metal antagonist BAL (2,3
      dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse
      effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating
      moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously
      recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest
      that BAL in such cases acted as a shuttling Pb transporter from the intra- to the
      extracellular space. The present paper discusses if a combination of the
      extracellularly distributed DMSA with the ionophore, Monensin may provide a less
      toxic combination for Pb mobilization by increasing both the efflux of
      intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy
      with DMSA should be continued with several intermittent courses. DMPS and DMSA
      are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more
      efficient agent against As poisoning. However, new insight indicates that a
      combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to
      obtain mobilization of the intracerebral deposits into the circulation for
      subsequent rapid urinary excretion.

PMID- 29063136
TI  - Coupling biological detection to liquid chromatography: a new tool in drug
      discovery.
AB  - Procedures to characterize drugs that can be obtained from plant extracts or
      combinatorial chemistry are tedious, and they consume considerable resources
      (e.g., animals) and time. Thus, we have looked for a way to streamline this
      process. We describe here a novel system for the pre-characterization of drugs
      based on liquid chromatography coupled to biological detection using perifused or
      perfused organs. This novel system allows the on-line detection of
      pharmacologically active substances in hydrosoluble mixtures from vegetal
      extracts or combinatorial chemistry libraries. Depending on the volume of drug
      solution and concentration of the samples, the procedure can work through either
      medium pressure liquid chromatography or HPLC, and it enables the fingerprints of
      drugs to be assessed based on their contractile activity on combinations of
      different isolated tissues. As an example, we show how the system can identify
      active fractions from an extract of Stevia rebaudiana Bertoni, an activity that
      was later associated with rebaudioside N. Coupling liquid chromatography to
      biological detection offers a rapid way to focus attention on active products in
      complex samples, mostly from hydrosoluble species, helping to considerably reduce
      the time and cost of the pre-characterization of drugs.

PMID- 29063137
TI  - The adverse drug reaction reporting assignment for specialist oncology nurses: a
      preliminary evaluation of quality, relevance and educational value in a
      prospective cohort study.
AB  - In a new prescribing qualification course for specialist oncology nurses, we
      thought that it is important to emphasize pharmacovigilance and adverse drug
      reaction (ADR) reporting. We aimed to develop and evaluate an ADR reporting
      assignment for specialist oncology nurses. The quality of report documentation
      was assessed with the "Clinical Documentation tool to assess Individual Case
      Safety Reports" (ClinDoc). The relevance of the reports was evaluated in terms of
      ADR seriousness, the listing for additional monitoring of the drug by European
      Medicines Agency (EMA), and lack of labelling information about the ADR. Nurses'
      opinions of the assignment were evaluated using an E-survey. Thirty-three ADRs
      were reported, 32 (97%) of which were well documented according to ClinDoc.
      Thirteen ADRs (39%) were "serious" according to CIOMS criteria. In five cases
      (15%), the suspect drugs were listed for additional monitoring by EMA and in
      seven cases (21%), the ADR was not mentioned in the Summary of Product
      Characteristics. Twenty-five (78.1%) of the 32 enrolled nurses completed the E
      survey. Most were > 45 years of age (68%), female (92%) and had extensive
      clinical experience (6-33 years). All agreed or completely agreed that the
      reporting assignment was useful, that it fitted in daily practice and that it
      increased their attention for medication/patient safety. A large majority (84.0%)
      agreed the assignment changed how they dealt with ADRs. Specialist oncology
      nurses are capable of reporting ADRs, and they considered the assignment useful.
      The assignment yielded valuable, relevant, and well-documented ADR reports for
      pharmacovigilance practice.

PMID- 29063138
TI  - Decision-making, somatic markers and emotion processing in opiate users.
AB  - RATIONALE: Opiate use is associated with deficits in decision-making. A possible
      explanation for these deficits is provided by the somatic marker hypothesis,
      which suggests that substance users may experience abnormal emotional responses
      during decision-making involving reward and punishment. This in turn may
      interfere with the brief physiological arousal, i.e. somatic markers that
      normally occur in anticipation of risky decisions. To date, the applicability of
      the somatic marker hypothesis to explain decision-making deficits has not been
      investigated in opiate users. OBJECTIVES: This study assessed whether decision
      making deficits in opiate users were related to abnormal emotional responses and
      reduced somatic markers. METHODS: Opiate users enrolled in an opiate substitute
      treatment program (n = 28) and healthy controls (n = 32) completed the Iowa
      Gambling Task (IGT) while their skin conductance responses (SCRs) were recorded.
      Participants' emotional responses to emotion-eliciting videos were also recorded
      using SCRs and subjective ratings. RESULTS: Opiate users displayed poorer
      decision-making on the IGT than did controls. However, there were no differences
      between the groups in SCRs; both groups displayed stronger SCRs following
      punishment than following reward, and both groups displayed stronger anticipatory
      SCRs prior to disadvantageous decisions than advantageous decisions. There were
      no group differences in objective or subjective measures of emotional responses
      to the videos. CONCLUSIONS: The results suggest that deficits in emotional
      responsiveness are not apparent in opiate users who are receiving pharmacological
      treatment. Thus, the somatic marker hypothesis does not provide a good
      explanation for the decision-making deficits in this group.

PMID- 29063139
TI  - Dissociable effects of the kappa opioid receptor agonist nalfurafine on pain/itch
      stimulated and pain/itch-depressed behaviors in male rats.
AB  - RATIONALE: Nalfurafine is a G protein signaling-biased kappa opioid receptor
      (KOR) agonist approved in Japan for second-line treatment of uremic pruritus.
      Neither nalfurafine nor any other KOR agonist is currently approved anywhere for
      treatment of pain, but recent evidence suggests that G protein signaling-biased
      KOR agonists may have promise as candidate analgesics/antipruritics with reduced
      side effects compared to nonbiased or beta-arrestin-signaling-biased KOR
      agonists. OBJECTIVES: This study compared nalfurafine effects in rats using
      assays of pain-stimulated and pain-depressed behavior used previously to evaluate
      other candidate analgesics. Nalfurafine effects were also examined in
      complementary assays of itch-stimulated and itch-depressed behavior. METHODS:
      Intraperitoneal lactic acid (IP acid) and intradermal serotonin (ID 5HT) served
      as noxious and pruritic stimuli, respectively, in male Sprague Dawley rats to
      stimulate stretching (IP acid) or scratching (ID 5HT) or to depress positively
      reinforced operant responding in an assay of intracranial self-stimulation (ICSS;
      both stimuli). RESULTS: Nalfurafine was equipotent to decrease IP acid-stimulated
      stretching and ID 5HT-stimulated scratching; however, doses of nalfurafine that
      decreased these pain/itch-stimulated behaviors also decreased control ICSS
      performance. Moreover, nalfurafine failed to alleviate either IP acid- or ID 5HT
      induced depression of ICSS. CONCLUSIONS: These results suggest that nalfurafine
      induced decreases in pain/itch-stimulated behaviors may reflect nonselective
      decreases in motivated behavior rather than analgesia or antipruritus against the
      noxious and pruritic stimuli used here. This conclusion agrees with the absence
      of clinical data for nalfurafine analgesia and the weak clinical data for
      nalfurafine antipruritus. Nalfurafine bias for G protein signaling may not be
      sufficient for clinically safe and reliable analgesia or antipruritus.

PMID- 29063141
TI  - CmpX Affects Virulence in Pseudomonas aeruginosa Through the Gac/Rsm Signaling
      Pathway and by Modulating c-di-GMP Levels.
AB  - Pseudomonas aeruginosa is an ubiquitous organism which is able to infect and
      colonize many types of hosts including humans. Colonization of P. aeruginosa in
      chronic infections leads to the formation of biofilms, which are difficult to
      eradicate. P. aeruginosa is capable of regulating its virulence factors in
      response to external environment triggers and its signaling mechanism involves
      two-component regulatory systems and small molecules such as bis-(3'-5')-cyclic
      dimeric guanosine monophosphate. PA1611-RetS-GacS/A-RsmA/Y/Z is a key regulatory
      pathway in P. aeruginosa that controls several virulence factors and biofilm
      formation. We have previously identified a conserved cytoplasmic membrane protein
      cmpX (PA1775), as a regulator for PA1611 expression. In this study, we
      demonstrate that cmpX regulates virulence, and controls biofilm formation in P.
      aeruginosa as well as provide evidence showing that cmpX affects Gac/Rsm pathway,
      possibly by modulating intra-cellular c-di-GMP levels. A cmpX knockout showed
      significantly decreased promoter activity of exoS (PA1362) and increased activity
      of small RNA, RsmY. As compared to the wild-type PAO1, cmpX mutant had elevated
      intracellular c-di-GMP level as measured indirectly by cdrA (PA4625) activity, as
      well as increased expression of wspR (PA3702), a c-di-GMP synthase. The
      transcription of the major outer membrane porin gene oprF (PA1777), and sigma
      factor sigX (PA1776) was also significantly decreased in the cmpX mutant. Biolog
      phenotype microarray experiments further indicated that the cmpX knockout mutant
      had increased sensitivity to membrane detergents and antibiotics such as lauryl
      sulfobetaine, tobramycin, and vancomycin. These results point to a significant
      role of cmpX in P. aeruginosa virulence and colonization.

PMID- 29063143
TI  - The NAv1.7 blocker protoxin II reduces burn injury-induced spinal nociceptive
      processing.
AB  - : Controlling pain in burn-injured patients poses a major clinical challenge.
      Recent findings suggest that reducing the activity of the voltage-gated sodium
      channel Nav1.7 in primary sensory neurons could provide improved pain control in
      burn-injured patients. Here, we report that partial thickness scalding-type burn
      injury on the rat paw upregulates Nav1.7 expression in primary sensory neurons 3
      h following injury. The injury also induces upregulation in phosphorylated cyclic
      adenosine monophosphate response element-binding protein (p-CREB), a marker for
      nociceptive activation in primary sensory neurons. The upregulation in p-CREB
      occurs mainly in Nav1.7-immunopositive neurons and exhibits a peak at 5 min and,
      following a decline at 30 min, a gradual increase from 1 h post-injury. The
      Nav1.7 blocker protoxin II (ProTxII) or morphine injected intraperitoneally 15
      min before or after the injury significantly reduces burn injury-induced spinal
      upregulation in phosphorylated serine 10 in histone H3 and phosphorylated
      extracellular signal-regulated kinase 1/2, which are both markers for spinal
      nociceptive processing. Further, ProTxII significantly reduces the frequency of
      spontaneous excitatory post-synaptic currents in spinal dorsal horn neurons
      following burn injury. Together, these findings indicate that using Nav1.7
      blockers should be considered to control pain in burn injury. KEY MESSAGES: *
      Burn injury upregulates Nav1.7 expression in primary sensory neurons. * Burn
      injury results in increased activity of Nav1.7-expressing primary sensory
      neurons. * Inhibiting Nav1.7 by protoxin II reduces spinal nociceptive
      processing. * Nav1.7 represents a potential target to reduce pain in burn injury.

PMID- 29063140
TI  - Biocide Selective TolC-Independent Efflux Pumps in Enterobacteriaceae.
AB  - Bacterial resistance to biocides used as antiseptics, dyes, and disinfectants is
      a growing concern in food preparation, agricultural, consumer manufacturing, and
      health care industries, particularly among Gram-negative Enterobacteriaceae, some
      of the most common community and healthcare-acquired bacterial pathogens. Biocide
      resistance is frequently associated with antimicrobial cross-resistance leading
      to reduced activity and efficacy of both antimicrobials and antiseptics.
      Multidrug resistant efflux pumps represent an important biocide resistance
      mechanism in Enterobacteriaceae. An assortment of structurally diverse efflux
      pumps frequently co-exist in these species and confer both unique and overlapping
      biocide and antimicrobial selectivity. TolC-dependent multicomponent systems that
      span both the plasma and outer membranes have been shown to confer clinically
      significant resistance to most antimicrobials including many biocides, however, a
      growing number of single component TolC-independent multidrug resistant efflux
      pumps are specifically associated with biocide resistance: small multidrug
      resistance (SMR), major facilitator superfamily (MFS), multidrug and toxin
      extruder (MATE), cation diffusion facilitator (CDF), and proteobacterial
      antimicrobial compound efflux (PACE) families. These efflux systems are a growing
      concern as they are rapidly spread between members of Enterobacteriaceae on
      conjugative plasmids and mobile genetic elements, emphasizing their importance to
      antimicrobial resistance. In this review, we will summarize the known biocide
      substrates of these efflux pumps, compare their structural relatedness,
      Enterobacteriaceae distribution, and significance. Knowledge gaps will be
      highlighted in an effort to unravel the role that these apparent "lone wolves" of
      the efflux-mediated resistome may offer.

PMID- 29063144
TI  - [Grip strength measurement : Significance and boundaries].
AB  - BACKGROUND: Grip strength measurement is a widely used method for clinical as
      well as scientific purposes. In hand surgery, it is an essential component in the
      diagnosis of disease, treatment sequences and assessment. In epidemiological
      studies, it is a good predictor of healthy ageing or disease progression.
      PROBLEM: Measurement results and their interpretation can be influenced by many
      factors. The historical development of dynamometry, measurement technology and
      the standard values in various population groups are presented. Comparisons with
      standard values should only be made using current tables because the grip
      strength has changed in recent decades. Assessment of the voluntarily submaximal
      grip strength remains problematic. Proposals are made for how to assess grip
      strength during the evaluation.

PMID- 29063142
TI  - Molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia.
AB  - The FGFR3 gene encodes fibroblast growth factor receptor 3 protein, a negative
      regulator of chondrogenesis. Gain-of-function mutations result in constitutively
      activated FGFR3, leading to aberrant signal transduction, and accounting for
      inhibition of chondrocyte proliferation and differentiation. Generally, these
      pathogenic mutations maintain FGFR3 in an active state and cause diverse
      phenotypes in patients with skeletal dysplasia. For decades, studies have
      revealed the molecular mechanisms of constitutively activated FGFR3 and relevant
      therapeutic strategies. By modulating the FGFR3-induced signalling pathway with
      methods such as blocking binding between ligands and receptors, blocking tyrosine
      kinase activities, or antagonising the FGFR3 downstream signalling pathway, these
      strategies offer the possibility to ameliorate FGFR3 gene-related skeletal
      dysplasia phenotypes. In this review, we describe the mechanisms of potential
      therapeutic targets and underlying regulators and then systematically review
      molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia based
      on current knowledge.

PMID- 29063145
TI  - [Humeral and glenoid bone loss in shoulder arthroplasty : Classification and
      treatment principles].
AB  - TECHNIQUE: The treatment of bone defects in primary shoulder arthroplasty has
      evolved due to more detailed diagnostic tools, 3D planning and expanded
      indications for reverse shoulder arthroplasty. Glenoid bone defects combined with
      chronic posterior subluxation of the humeral head are gradually being treated by
      glenoid reconstruction and reverse implants even if the rotator cuff is still
      intact. The treatment of advanced bone loss due to glenoid loosening has been
      facilitated by bone augmentation using a cementless fixation as proposed by
      Norris. Precise pre-operative planning using reformatted computed tomography (CT)
      and dedicated instruments is recommended in primary and revision arthroplasty.
      RESULTS: Revision rates and complications are high for revision surgery in
      extended glenoid and humeral bone loss. Functional results are limited in these
      cases, particularly after multiple operations and damage of the soft tissue
      envelope.

PMID- 29063146
TI  - Progressive glenoid bone loss caused by erosion in humeral head resurfacing.
AB  - BACKGROUND: Cementless surface replacement of the shoulder represents an
      alternative to conventional stemmed anatomic prostheses. Glenoid erosion is a
      well-known complication in hemiarthroplasty. However, there is limited data
      concerning radiographic evaluation and prognostic factors for this phenomenon.
      OBJECTIVES: The aim of our study was to determine the development of glenoid
      erosion following shoulder resurfacing using a new measurement technique and
      detect potential prognostic factors. MATERIALS AND METHODS: We performed a
      retrospective analysis on 38 shoulders undergoing humeral head resurfacing with a
      mean follow-up of 65.4 +/- 43 months. Clinical and radiographic evaluation
      followed a standardized protocol including pre- and postoperative Constant score,
      active range of motion, and X-rays in true anteroposterior view. Three
      independent observers performed measurements of glenoid erosion. RESULTS: We
      found good interobserver reliability for glenoid erosion measurements (intraclass
      correlation coefficient [ICC] 0.74-0.78). Progressive glenoid erosion was present
      in all cases, averaging 5.5 +/- 3.9 mm at more than 5 years' follow-up. Male
      patients demonstrated increased glenoid bone loss within the first 5 years (p <
      0.04). The mean Constant score improved to 55.4 +/- 23.6 points at the latest
      follow-up. Younger age was correlated to increased functional outcome. Revision
      rate due to painful glenoid erosion was 37%. CONCLUSIONS: Glenoid erosion can be
      routinely expected in patients undergoing humeral head resurfacing. Painful
      glenoid erosion leads to deterioration in functional outcome and necessitates
      revision surgery in a high percentage of cases.

PMID- 29063148
TI  - Tide as Steering Factor in Structuring Archaeal and Bacterial Ammonia-Oxidizing
      Communities in Mangrove Forest Soils Dominated by Avicennia germinans and
      Rhizophora mangle.
AB  - Mangrove species are adapted to grow at specific zones in a tidal gradient. Here
      we tested the hypothesis that the archaeal and bacterial ammonia-oxidizing
      microbial communities differ in soils dominated by the mangrove species Avicennia
      germinans and Rhizophora mangle. Two of the sampling locations were tidal
      locations, while the other location was impounded. Differences in the community
      compositions of ammonia-oxidizing archaea (AOA) and bacteria (AOB) were analyzed
      by denaturing gradient gel electrophoresis (DGGE) of amoA genes and by MiSeq 16S
      rRNA gene-sequencing. The abundances of AOA and AOB were established by
      quantitative PCR of amoA genes. In addition, we analyzed the total microbial
      community composition based on 16S rRNA genes and explored the influence of soil
      physicochemical properties underneath Avicennia germinans and Rhizophora mangle
      on microbial communities. AOA were always more abundant than AOB, but the effect
      of mangrove species on total numbers of ammonia oxidizers was location-specific.
      The microbial communities including the ammonia oxidizers in soils associated
      with A. germinans and R. mangle differed only at the tidal locations. In
      conclusion, potential site-specific effects of mangrove species on soil microbial
      communities including those of the AOA and AOB are apparently overruled by the
      absence or presence of tide.

PMID- 29063147
TI  - Importance of Local and Regional Scales in Shaping Mycobacterial Abundance in
      Freshwater Lakes.
AB  - Biogeographical studies considering the entire bacterial community may
      underestimate mechanisms of bacterial assemblages at lower taxonomic levels. In
      this context, the study aimed to identify factors affecting the spatial and
      temporal dynamic of the Mycobacterium, a genus widespread in aquatic ecosystems.
      Nontuberculous mycobacteria (NTM) density variations were quantified in the water
      column of freshwater lakes at the regional scale (annual monitoring of 49 lakes
      in the Paris area) and at the local scale (2-year monthly monitoring in Creteil
      Lake) by real-time quantitative PCR targeting the atpE gene. At the regional
      scale, mycobacteria densities in water samples ranged from 6.7 * 103 to 1.9 * 108
      genome units per liter. Density variations were primarily explained by water pH,
      labile iron, and dispersal processes through the connection of the lakes to a
      river. In Creteil Lake, no spatial variation of mycobacterial densities was
      noticed over the 2-year monthly survey, except after large rainfall events.
      Indeed, storm sewer effluents locally and temporarily increased NTM densities in
      the water column. The temporal dynamic of the NTM densities in Creteil Lake was
      associated with suspended solid concentrations. No clear seasonal variation was
      noticed despite a shift in NTM densities observed over the 2012-2013 winter.
      Temporal NTM densities fluctuations were well predicted by the neutral community
      model, suggesting a random balance between loss and gain of mycobacterial taxa
      within Creteil Lake. This study highlights the importance of considering multiple
      spatial scales for understanding the spatio-temporal dynamic of bacterial
      populations in natural environments.

PMID- 29063150
TI  - Drug safety in pregnancy: the German Embryotox institute.
AB  - Since 1988, the German Embryotox institute combines individual counselling of
      pregnant women and their health care providers (HCP) with research on drug safety
      in pregnancy. In addition, Embryotox offers web-based information which covers
      the most important and most frequently requested pharmaceutical substances. In
      contrast to ready-made drug risk information in package leaflets and other
      product information, individual counselling considers different clinical settings
      such as (1) looking for a drug of choice or planning pregnancy under medication,
      (2) risk assessment of a particular drug that has already been taken during an
      (unplanned) pregnancy and (3) evaluation of an adverse pregnancy outcome in
      association with a particular medication. Using the three established
      developmental toxicants valproic acid, isotretinoin, and renin-angiotensin
      aldosterone system (RAAS) inhibitors as an example, the need of detailed
      information is illustrated. Through the risk communication process, pregnancy
      outcome data are routinely collected by Embryotox. This approach uses the
      advantages of a pre-existing communication structure and of dealing with
      motivated responders. Engagement in the treatment plan facilitates receiving
      reliable data on drug exposure as well as detailed follow-up data. Based on these
      patient records, prospective datasets are evaluated in observational cohort
      studies in comparison to non-exposed control cohorts. In addition, retrospective
      datasets received as suspected adverse drug reactions from multiple German
      sources allow a screening for signals of teratogenicity and distinct patterns of
      developmental toxicity. Clinical expertise in specialties such as teratology,
      paediatrics, embryology, obstetrics and human genetics are required to ensure
      high-quality assessment of drug safety in pregnancy.

PMID- 29063151
TI  - Correction to: A case series of lateral opening wedge high tibial osteotomy for
      valgus malalignment.
AB  - Unfortunately, one of the co-author affiliation was incorrect in the original
      publication of this article. The correct affiliation is given below: Abdulaziz Z.
      Alomar, King Khalid University Hospital, College of Medicine, King Saud
      University, Riyadh, Saudi Arabia.

PMID- 29063149
TI  - Primary care physicians report high trust in and usefulness of the Stockholm drug
      and therapeutic committee's list of recommended essential medicines (the 'Wise
      List').
AB  - PURPOSE: Inappropriate use of medicines causes increased morbidity, mortality,
      adverse drug reactions, therapeutic failures and drug resistance as well as
      wastes valuable resources. Evidence-based cost-effective treatment
      recommendations of essential medicines are a way of avoiding these. We assessed
      primary care prescribers' knowledge about and perceptions of an essential
      medicines formulary, as well as the reasons for adhering to the recommendations.
      METHODS: We conducted a web based questionnaire survey targeting all physicians
      working in the primary healthcare of the Stockholm healthcare region (2.3 million
      inhabitants), regarding the knowledge of, attitudes to and usefulness of the
      essential medicines formulary of the Stockholm Drug and Therapeutics Committee,
      the so-called Wise List. RESULTS: Of the 1862 physicians reached by our e-mail
      invitations, 526 (28%) participated in the survey. All but one respondent knew of
      the formulary, and 72% used it at least once a week when prescribing. The main
      reason for using the formulary was evidence-based prescribing; 97% trusted the
      guidelines, and almost all (98%) found the content easy to understand. At the
      same time, many prescribers thought that the annual changes of some
      recommendations were too frequent, and some felt that a national formulary would
      increase its trustworthiness. CONCLUSIONS: We found that the essential medicines
      formulary was widely used and trusted by the prescribers. The high uptake of the
      treatment recommendations could be due to the Stockholm Drug and Therapeutics
      Committee's transparent process for developing recommendations involving
      respected experts and clinicians using strict criteria for handling potential
      conflicts of interest, feedback to prescribers, continuous medical education and
      minor financial incentives.

PMID- 29063152
TI  - Bone grafts used for arthroscopic glenoid reconstruction restore the native
      glenoid anatomy.
AB  - PURPOSE: Recurrent anterior instability of the glenohumeral joint is a demanding
      condition, especially in cases of glenoid bone loss. Various treatment options
      have been described, such as arthroscopic grafting techniques and the Latarjet
      procedure. In this study, the degree to which an arthroscopically applied iliac
      crest graft restores the glenoid anatomy was evalutated. METHODS: Nine patients
      (three women and six men) with an average age of 31 +/- 9 years (21-46 years) who
      were treated with an arthroscopic iliac crest graft technique were included in
      this study. After a mean follow up of 34 +/- 10 months (19-50 months) after the
      procedure, MRI scans of both shoulders were performed and the glenoid width,
      Glenoid Index (GI), Pixel Signal intensity (PSI), thickness of the tissue
      covering the articular aspect of the graft, inclination, version, concavity and
      balance stability angle were measured. RESULTS: All scans showed the cultivation
      of tissue on the graft, which visually resembled the cartilage of the native
      ipsilateral glenoid. Additionally, reshaping of the graft to repair the glenoid
      configuration could be observed. Glenoid width (p = 0.022) and GI (p < 0.001)
      increased significantly through surgery. The tissue examined on the graft showed
      a significant pixel intensity gap (p = 0.017) but comparable thickness (n.s.) in
      relation to native cartilage. The remaining parameters did not differ
      significantly between both shoulders. CONCLUSION: In the cohort presented, iliac
      crest grafts were able to restore the glenoid configuration, and the glenoid was
      re-shaped to its native contour. Additionally, cartilage-like scar tissue with
      similar thickness as healthy cartilage was formed on the articular side of the
      graft. These results suggest that glenoid reconstruction is not only important
      for prevention of recurrence, but also for restoration of the native glenoid
      anatomy. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

PMID- 29063155
TI  - [Regional life expectancy rankings : Methodological artefacts in population
      updates].
AB  - For the calculation of life expectancy on a regional level, data from the
      mortality statistics and population numbers are needed. The latter are derived
      from population censuses, which have to be undertaken every 10 years according to
      the EU regulation No. 763/2008. In Germany, the last census took place in 2011
      (Census 2011). The current population numbers are calculated on the basis of the
      most recent population census (population update). Births, deaths, immigration
      and migration, in addition to other data, are taken into account in this
      calculation. However, with passing time since the last census, inaccuracies in
      population updates may increase, which can affect the value of life expectancy
      calculations.Based on the comparison of life expectancy rankings, the impact and
      extent of changing over from the 1987 to the more recent 2011 census for regional
      comparisons were examined in two parts of Germany, Bavaria and North Rhine
      Westphalia. As expected, the results show that larger changes in the calculated
      life expectancy result from larger changes in population statistics. However,
      noteworthy changes in life expectancy rankings do not necessarily follow larger
      changes in the population numbers. Regional life expectancy rankings are
      potentially always influenced by inaccuracies in the underlying population
      statistics. This should be taken into account when interpreting such small-scale
      differences.

PMID- 29063154
TI  - [Primary and secondary data on dementia care as an example of regional health
      planning].
AB  - BACKGROUND: Health service planning that takes into account as far as possible
      the regional needs and regional discrepancies is a controversial health issue in
      Germany. OBJECTIVES: In a pilot scheme, we tested a planning process for regional
      healthcare services, based on the example of dementia care. The aim of this
      article is to present the strengths and limitations of this planning process.
      MATERIALS AND METHODS: We developed an indicator set for dementia care based on
      routine regional data obtained from two German statutory health insurance
      companies. Additionally, primary data based on a questionnaire sent to all GPs in
      the area were evaluated. These data were expanded through the addition of
      official socio-demographic population data. Procedures and evaluation strategies,
      discussion of the results and the derivation of planning measures followed, in
      close agreement with a group of local experts. RESULTS: Few epidemiological data
      on regional variations in health care planning are publicly available. Secondary
      data from statutory health insurance companies can be assessed to support the
      estimation of regional health care needs, but interpretation is difficult. The
      use of surveys to collect primary data, and the assessment of results by the
      local health board may facilitate interpretation and may contribute towards more
      valid statements regarding regional health planning. CONCLUSIONS: Despite the
      limited availability of data and the considerable efforts involved in data
      analysis, the project demonstrates how needs-based health service planning can be
      carried out in a small region, taking into account the increasing demands of the
      local health care providers and the special local features.

PMID- 29063153
TI  - The posterior horn of the lateral meniscus is a reliable novel landmark for
      femoral tunnel placement in ACL reconstruction.
AB  - PURPOSE: Femoral tunnel placement is essential for good outcome in anterior
      cruciate ligament (ACL) reconstruction. In the past, several attempts have been
      made to optimize femoral tunnel placement. It was observed that the posterior
      horn of the lateral meniscus was always located directly below to the desired
      femoral ACL tunnel position, when the knee was brought to deep flexion (> 120
      degrees ). The goal of the present study was to verify the hypothesis that the
      posterior horn of the lateral meniscus can be used as a landmark for femoral
      tunnel placement. METHODS: Out of a consecutive series of ACL reconstructions
      done by a single surgeon, 55 lateral radiographs were evaluated according to the
      quadrant method by Bernard and Hertel. Additionally, on anterior-posterior
      radiographs the femoral tunnel angle was determined. RESULTS: In the present case
      series the posterior horn of the lateral meniscus could be identified and used as
      a landmark for femoral tunnel placement in all cases. The mean tunnel depth was
      24 +/- 5.1% and the mean tunnel height was 31.3 +/- 5.7%. The mean femoral tunnel
      angle was 41 +/- 4.9 degrees  using the anatomical axis as a reference. Compared
      to previous cadaver studies the data of the present study were within their
      anatomical range of the native ACL insertion site. CONCLUSION: The suggested
      technique using the posterior horn of the lateral meniscus as a landmark for
      femoral tunnel placement showed reproducible results and matches the native ACL
      insertion site compared to previous cadaveric studies. In particular, non
      experienced ACL surgeons will benefit from this apparent landmark and the
      corresponding easy-to-use ACL reconstruction method. LEVEL OF EVIDENCE: IV.

PMID- 29063156
TI  - [A spatially explicit analysis of traffic accidents involving pedestrians and
      cyclists in Berlin].
AB  - BACKGROUND: In many German cities and counties, sustainable mobility concepts
      that strengthen pedestrian and cyclist traffic are promoted. From the
      perspectives of urban development, traffic planning and public healthcare, a
      spatially differentiated analysis of traffic accident data is decisive.
      OBJECTIVES: 1) The identification of spatial and temporal patterns of the
      distribution of accidents involving cyclists and pedestrians, 2) the
      identification of hotspots and exploration of possible underlying causes and 3)
      the critical discussion of benefits and challenges of the results and the
      derivation of conclusions. MATERIAL AND METHODS: Spatio-temporal distributions of
      data from accident statistics in Berlin involving pedestrians and cyclists from
      2011 to 2015 were analysed with geographic information systems (GIS). RESULTS:
      While the total number of accidents remains relatively stable for pedestrian and
      cyclist accidents, the spatial distribution analysis shows, however, that there
      are significant spatial clusters (hotspots) of traffic accidents with a strong
      concentration in the inner city area. CONCLUSIONS: In a critical discussion, the
      benefits of geographic concepts are identified, such as spatially explicit health
      data (in this case traffic accident data), the importance of the integration of
      other data sources for the evaluation of the health impact of areas (traffic
      accident statistics of the police), and the possibilities and limitations of
      spatial-temporal data analysis (spatial point-density analyses) for the
      derivation of decision-supported recommendations and for the evaluation of policy
      measures of health prevention and of health-relevant urban development.

PMID- 29063157
TI  - [Mental disorders of working age : Evaluation of the administrative incidence and
      prevalence as well as regional differences in Lower Saxony on the basis of
      secondary data from a statutory health insurance provider].
AB  - BACKGROUND: Mental disorder is the subject of ever-increasing attention in the
      field of public health. However, the actual number of such cases is difficult to
      determine owing to the lack of comprehensive longitudinal studies. OBJECTIVES:
      The administrative incidence and prevalence of mental disorders were estimated on
      the basis of data from 2010 to 2013 provided by the health insurance company AOK,
      Lower Saxony, and were assessed according to age and gender. Additionally,
      possible correlations between local conditions and the occurrence of diagnosed
      mental disorders were examined for both urban and rural districts. MATERIALS AND
      METHODS: Analyses were conducted using the secondary datasets of 1.5 million
      persons born between 1940 and 1994 who had been continuously insured throughout
      the period specified. Only documented diagnoses from outpatient care were taken
      into account. RESULTS: One third of the insured persons showed at least one
      documented diagnosis of a mental disorder within a 12-month period. In
      approximately 11 out of 100 cases, there was a newly documented diagnosis in
      2012. With the exception of cases relating to psychotropic substance use, women
      were significantly more frequently affected than men. Age-specific differences
      were also determined. At a regional level, in relation to administrative
      prevalence, mental disorders showed positive correlations in the density of
      doctors and psychotherapists. Moreover, regions with a high rate of unemployment
      generally show a higher prevalence of mental disorders. CONCLUSION: Despite
      certain limitations, the use of administrative incidence and prevalence data is a
      viable approach to assessing gender- and age-specific, and regional differences.
      Our regional analyses suggest a correlation between the local job situation and
      the level of regional administrative prevalence.

PMID- 29063158
TI  - [The cartographic depiction of regional variation in morbidity : Data analysis
      options using the example of the small-scale cancer atlas for Schleswig
      Holstein].
AB  - The cancer registry in Germany collects area-wide small-area data that can be
      presented in themes (disease mapping). Because of the occurrence of random
      extreme values of rates, mapping without prior spatial-statistical data analysis
      is problematic from a methodological and risk-communicative viewpoint - the
      extreme values easily mislead the card reader and obscure actual spatial
      patterns.The problem of data instability can generally be met by aggregation or
      by smoothing. The cancer atlas for Schleswig-Holstein is based on data from 1142
      municipalities (median population: 721) for the diagnostic years 2001-2010. Maps
      for incidence (as a standardized incidence ratio), mortality (as a standardized
      mortality ratio), and relative survival (as a relative excess risk) were smoothed
      by using a Bayesian method (BYM model). The maps show that spatial differences
      can be made visible by smoothing.Data aggregation is the methodically simpler
      way, but means a loss of information. The atlas shows that small-scale mapping is
      possible while preserving the entire spatial information. The method of smoothing
      is complex, but useful for generating hypotheses. The spatial patterns found are
      complex, difficult to interpret, and require the collaboration of specialists
      from different professions, because of the diverse influencing factors (data
      collection, lifestyle factors, early detection, risk factors, etc.). The effort
      required to explain the methodology in a language easy to understand should not
      be underestimated.

PMID- 29063160
TI  - Elevation in Sclerostin After Exercise: Is It Affected by Age and Sex?

PMID- 29063159
TI  - Fibroblast Growth Factor (FGF) 23 Regulates the Plasma Levels of Parathyroid
      Hormone In Vivo Through the FGF Receptor in Normocalcemia, But Not in
      Hypocalcemia.
AB  - The calcium and phosphate homeostasis is regulated by a complex interplay between
      parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and calcitriol.
      Experimental studies have demonstrated an inhibitory effect of FG23 on PTH
      production and secretion; the physiological role of this regulation is however
      not well understood. Surprisingly, in uremia, concomitantly elevated FGF23 and
      PTH levels are observed. The parathyroid gland rapidly loses its responsiveness
      to extracellular calcium in vitro and a functional parathyroid cell line has
      currently not been established. Therefore, the aim of the present investigation
      was to study the impact of FGF23 on the Ca2+/PTH relationship in vivo under
      conditions of normocalcemia and hypocalcemia. Wistar rats were allocated to
      treatment with intravenous recombinant FGF23 and inhibition of the FGF receptor
      in the setting of normocalcemia and acute hypocalcemia. We demonstrated that
      FGF23 rapidly inhibited PTH secretion and that this effect was completely blocked
      by inhibition of the FGF receptor. Furthermore, inhibition of the FGF receptor by
      itself significantly increased PTH levels, indicating that FGF23 has a
      suppressive tonus on the parathyroid gland's PTH secretion. In acute
      hypocalcemia, there was no effect of either recombinant FGF23 or FGF receptor
      inhibition on the physiological response to the low ionized calcium levels. In
      conclusion, FGF23 has an inhibitory tonus on PTH secretion in normocalcemia and
      signals through the FGF receptor. In acute hypocalcemia, when increased PTH
      secretion is needed to restore the calcium homeostasis, this inhibitory effect of
      FGF23 is abolished.

PMID- 29063161
TI  - Improving the baking quality of bread wheat by genomic selection in early
      generations.
AB  - KEY MESSAGE: Genomic selection shows great promise for pre-selecting lines with
      superior bread baking quality in early generations, 3 years ahead of labour
      intensive, time-consuming, and costly quality analysis. The genetic improvement
      of baking quality is one of the grand challenges in wheat breeding as the
      assessment of the associated traits often involves time-consuming, labour
      intensive, and costly testing forcing breeders to postpone sophisticated quality
      tests to the very last phases of variety development. The prospect of genomic
      selection for complex traits like grain yield has been shown in numerous studies,
      and might thus be also an interesting method to select for baking quality traits.
      Hence, we focused in this study on the accuracy of genomic selection for
      laborious and expensive to phenotype quality traits as well as its selection
      response in comparison with phenotypic selection. More than 400 genotyped wheat
      lines were, therefore, phenotyped for protein content, dough viscoelastic and
      mixing properties related to baking quality in multi-environment trials 2009
      2016. The average prediction accuracy across three independent validation
      populations was r = 0.39 and could be increased to r = 0.47 by modelling major
      QTL as fixed effects as well as employing multi-trait prediction models, which
      resulted in an acceptable prediction accuracy for all dough rheological traits (r
      = 0.38-0.63). Genomic selection can furthermore be applied 2-3 years earlier than
      direct phenotypic selection, and the estimated selection response was nearly
      twice as high in comparison with indirect selection by protein content for baking
      quality related traits. This considerable advantage of genomic selection could
      accordingly support breeders in their selection decisions and aid in efficiently
      combining superior baking quality with grain yield in newly developed wheat
      varieties.

PMID- 29063162
TI  - Exhaled breath condensate methods adapted from human studies using longitudinal
      metabolomics for predicting early health alterations in dolphins.
AB  - Monitoring health conditions is essential to detect early asymptomatic stages of
      a disease. To achieve this, blood, urine and breath samples are commonly used as
      a routine clinical diagnostic. These samples offer the opportunity to detect
      specific metabolites related to diseases and provide a better understanding of
      their development. Although blood samples are commonly used routinely to monitor
      health, the implementation of a relatively noninvasive technique, such as exhaled
      breath condensate (EBC) analysis, may further benefit the well-being of both
      humans and other animals. EBC analysis can be used to track possible physical or
      biochemical alterations caused by common diseases of the bottlenose dolphin
      (Tursiops truncatus), such as infections or inflammatory-mediated processes. We
      have used an untargeted metabolomic method with liquid chromatography-mass
      spectrometry analysis of EBC samples to determine biomarkers related to disease
      development. In this study, five dolphins under human care were followed up for 1
      year. We collected paired blood, physical examination information, and EBC
      samples. We then statistically correlated this information to predict specific
      health alterations. Three dolphins provided promising case study information
      about biomarkers related to cutaneous infections, respiratory infections, dental
      disease, or hormonal changes (pregnancy). The use of complementary liquid
      chromatography platforms, with hydrophilic interaction chromatography and reverse
      phased columns, allowed us to detect a wide spectrum of EBC biomarker compounds
      that could be related to these health alterations. Moreover, these two analytical
      techniques not only provided complementary metabolite information but in both
      cases they also provided promising diagnostic information for these health
      conditions. Graphical abstract Collection of the exhaled condensed breath from a
      bottlenose dolphin from U.S. Navy Marine Mammal Program (MMP).

PMID- 29063163
TI  - Development of an integrated method of concentration and immunodetection of
      bacteria.
AB  - The microbial quality of water is a key aspect to avoid environmental and public
      health problems. The low pathogen concentration needed to produce a disease
      outbreak makes it essential to process large water volumes and use sensitive and
      specific methods such as immunoassays for its detection. In the present work, we
      describe the development of a device based on microfiltration membranes to
      integrate the concentration and the immunodetection of waterborne bacteria. A
      microfiltration membrane treatment protocol was designed to reduce the non
      specific binding of antibodies, for which different blocking agents were tested.
      Thus, the proof of concept of the microbial detection system was also carried out
      using Escherichia coli as the bacterial pathogen model. E. coli suspensions were
      filtered through the membranes at 0.5 mL s-1, and the E. coli concentration
      measurements were made by absorbance, at 620 nm, of the resultant product of the
      enzymatic reaction among the horseradish peroxidase (HRP) bonded to the antibody,
      and the substrate 3,3',5,5'-tetramethylbenzidine (TMB). The results showed that
      the homemade concentration system together with the developed membrane treatment
      protocol is able to detect E. coli cells with a limit of detection (LoD) of about
      100 CFU in 100 mL. Graphical abstract Scheme of the integrated method of
      concentration and immunodetection of bacteria.

PMID- 29063164
TI  - Pre-concentration and separation of bacteria by volume coupling electrophoresis
      on supercritical water-etched fused silica capillary with two segments of
      different internal diameters and inner surface roughnesses.
AB  - The transient isotachophoretic stacking and sweeping was used for the on-line
      large-volume sample pre-concentration of bacteria, Escherichia coli and
      Staphylococcus aureus cells (methicillin-susceptible or methicillin-resistant),
      in the initial stage of micellar electrokinetic chromatography using a non
      ionogenic surfactant or of capillary electrophoresis, respectively. These
      procedures were employed in single-piece fused silica capillary etched with
      supercritical water with two different internal diameter segments featuring
      different inner surface roughness. Large volumes (maximum 2.8 MUL) of the high
      conductivity sample matrices, physiological saline solution, urine or blood (with
      purification step), spiked with examined cells were injected into the wider end
      of a capillary with an inlet inner diameter 195 MUm. This novel on-line
      combination of preconcentration strategies for cells produced an up to 680-fold
      increase in sensitivity for E. coli or S. aureus cells. The average calculated
      resolutions, R, for five selected methicillin-susceptible or methicillin
      resistant strains were found to be 6.3 for the agar-cultivated and 14.9 for the
      blood-incubated cells. A low number of bacteria similar to those in clinical
      samples were also tested. The modified surface roughness step helped to
      significantly narrow the cell zones and to increase resolution. The migration
      velocities of E. coli agar-cultivated and blood-incubated cells were
      approximately the same as those of S. aureus, probably due to the minimal
      differences in their surface properties. This procedure, on-line pre
      concentration and separation of bacteria, is rapid and provides good
      reproducibility and repeatability.

PMID- 29063165
TI  - Simultaneous analysis of aminoglycosides with many other classes of drug residues
      in bovine tissues by ultrahigh-performance liquid chromatography-tandem mass
      spectrometry using an ion-pairing reagent added to final extracts.
AB  - The way to maximize scope of analysis, sample throughput, and laboratory
      efficiency in the monitoring of veterinary drug residues in food animals is to
      determine as many analytes as possible as fast as possible in as few methods as
      possible. Capital and overhead expenses are also reduced by using fewer
      instruments in the overall monitoring scheme. Traditionally, the highly polar
      aminoglycoside antibiotics require different chromatographic conditions from
      other classes of drugs, but in this work, we demonstrate that an ion-pairing
      reagent (sodium 1-heptanesulfonate) added to the combined final extracts from two
      sample preparation methods attains good separation of 174 targeted drugs,
      including 9 aminoglycosides, in the same 10.5-min ultrahigh-performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The full method
      was validated in bovine kidney, liver, and muscle tissues according to US
      regulatory protocols, and 137-146 (79-84%) of the drugs gave between 70 and 120%
      average recoveries with <= 25% RSDs in the different types of tissues spiked at
      0.5, 1, and 2 times the regulatory levels of interest (10-1000 ng/g depending on
      the drug). This method increases sample throughput and the possible number of
      drugs monitored in the US National Residue Program, and requires only one UHPLC
      MS/MS method and instrument for analysis rather than two by the previous scheme.
      Graphical abstract Outline of the streamlined approach to monitor 174 veterinary
      drugs, including aminoglycosides, in bovine tissues by combining two extracts of
      the same sample with an ion-pairing reagent for analysis by UHPLC-MS/MS.

PMID- 29063167
TI  - [Management and outcome of type II fractures of the odontoid process].
AB  - BACKGROUND: The most effective treatment of type II dens fractures according to
      Anderson and D'Alonzo remains controversial as there is no guidance on the choice
      of conservative or surgical therapy and if the anterior or the posterior approach
      is more advantageous. In 1993 Eysel and Roosen showed that the consolidation rate
      of type II odontoid fractures mostly depends on the morphology of the fracture
      and established a classification with corresponding treatment recommendations.
      OBJECTIVE: The investigation aimed at clarifying the outcome of type II dens
      fractures treated according to the recommendations of Eysel and Roosen. MATERIAL
      AND METHODS: Data of dens fractures from 72 patients were analyzed and
      categorized according to the Eysel and Roosen classification. Furthermore, the
      treatment was analyzed and the outcome was evaluated retrospectively using
      radiographs acquired during follow-up. RESULTS: The mean age of the 72 patients
      was 70.7 years. Of the patients 19.4% suffered from type A, 75% from type B and
      5.6% from type C fractures according to Eysel and Roosen. Out of the 72 patients
      45 were assessed by computed tomography (CT) scan during follow-up. According to
      the recommendations of the authors 34 of the 41 patients with type A or type B
      fractures underwent anterior screw fixation of the dens and 3 out of the 4
      patients with a type C fracture underwent a dorsal C1 and C2 fusion. After a mean
      follow-up of 7 months non-union was observed in 15.6% of the patients whereby 6
      of the these patients were treated by surgery and 1 patient was managed
      conservatively. All of the patients who developed a non-union had a type B
      fracture. CONCLUSION: The simple clinical applicability together with the low
      rate of non-union development shows that the Eysel and Roosen classification
      appears to be a suitable guide for clinical use when deciding on the appropriate
      treatment regimen.

PMID- 29063169
TI  - [Importance of C1 pedicle screws in the Goel-Harms technique].

PMID- 29063168
TI  - [Modified Goel-Harms technique using C1 pedicle screws].

PMID- 29063166
TI  - Heart irradiation reduces microvascular density and accumulation of HSPA1 in
      mice.
AB  - PURPOSE: Improvement of radiotherapy techniques reduces the exposure of normal
      tissues to ionizing radiation. However, the risk of radiation-related late
      effects remains elevated. In the present study, we investigated long-term effects
      of radiation on heart muscle morphology. MATERIALS AND METHODS: We established a
      mouse model to study microvascular density (MVD), deposition of collagen fibers,
      and changes in accumulation of heat shock 70 kDa protein 1 (HSPA1) in irradiated
      heart tissue. Hearts of C57BL/6 mice received a single dose of X-ray radiation in
      the range 0.2-16 Gy. Analyses were performed 20, 40, and 60 weeks after
      irradiation. RESULTS: Reduction in MD was revealed as a long-term effect observed
      20-60 weeks after irradiation. Moreover, a significant and dose-dependent
      increase in accumulation of HSPA1, both cytoplasmic and nuclear, was observed in
      heart tissues collected 20 weeks after irradiation. We also noticed an increase
      in collagen deposition in hearts treated with higher doses. CONCLUSIONS: This
      study shows that some changes induced by radiation in the heart tissue, such as
      reduction in microvessel density, increase in collagen deposition, and
      accumulation of HSPA1, are observed as long-term effects which might be
      associated with late radiation cardiotoxicity.

PMID- 29063170
TI  - [Neuromodulation of lower urinary tract dysfunction].
AB  - Neuromodulative procedures such as transcutaneous electrical nerve stimulation
      (TENS), transcutaneous/percutaneous tibial nerve stimulation (TTNS/PTNS), and
      sacral neuromodulation (SNM) are promising second-line treatments for refractory
      lower urinary tract dysfunction. Using these therapies, both storage and voiding
      disorders but also bowel dysfunction might be successfully treated. Although the
      mechanism of action of neuromodulation is not well understood, it seems to
      involve modulation of spinal cord reflexes and brain networks by peripheral
      afferents (genital/rectal, tibial and sacral afferents in the case of TENS,
      TTNS/PTNS, and SNM, respectively). Neuromodulative procedures might also be
      highly effective in the most desperate situations and further relevant
      developments are expected so that these innovative techniques will most likely
      become even more important in urology.

PMID- 29063171
TI  - [Neuroendocrine prostate cancer].
AB  - Neuroendocrine prostate cancer (NEPC) mostly occurs as a treatment-emergent
      adaptive response under the pressure of intensive androgen deprivation treatment
      (t-NEPC). Approximately 30-40% of patients with metastatic castration-resistant
      prostate cancer (mCRPC) also have neuroendocrine involvement. In contrast primary
      small cell prostate cancer is very rare (<1%). A t-NEPC should be clinically
      suspected in patients who have particularly aggressive mCRPC but a
      disproportionately low prostate-specific antigen (PSA) level and elevated
      neuroendocrine tumor markers, such as chromogranin A and neuron-specific enolase.
      The initial Gleason score was shown to be an independent factor correlated to the
      risk of development of t-NEPC. Treatment is oriented to that of small cell lung
      cancer. In patients with negative PSA levels, chemotherapy with cisplatin and
      etoposide is the first line treatment, for which response rates in the range of
      30-60% with a median survival time of usually less than 1 year can be achieved.
      In patients with much higher serum PSA levels, chemotherapy with carboplatin plus
      docetaxel should be considered.

PMID- 29063172
TI  - Improved thermostability of a metagenomic glucose-tolerant beta-glycosidase based
      on its X-ray crystal structure.
AB  - MeBglD2, a metagenomic beta-glycosidase, is stimulated by various saccharides,
      including D-glucose, D-xylose, and maltose, and it promotes the enzymatic
      saccharification of plant biomass. To improve the thermostability of MeBglD2, its
      X-ray crystal structure was analyzed, and the amino acid residues responsible for
      its thermostability were identified using the structural information. Mutations
      in His8, Asn59, and Gly295 improved the thermostability of MeBglD2, and the
      combination of these mutations resulted in the highest thermostability. Compared
      with wild-type MeBglD2, thermostable MeBglD2 mutants promoted plant biomass
      saccharification using Trichoderma reesei cellulase. In addition to
      thermostability, the thermostable mutants exhibited higher tolerance to ethanol,
      dimethyl sulfoxide, and copper ions, indicating that the MeBglD2 mutants
      generated in this study were improved in their tolerance to not only high
      temperature but also to organic solvents and metal ions.

PMID- 29063173
TI  - Bovine single chain Fv antibody inhibits bovine herpesvirus-1 infectivity by
      targeting viral glycoprotein D.
AB  - Glycoprotein D (gD) of bovine herpesvirus-1 (BoHV-1) is essential for attachment
      and penetration of cells during infection and is a major target for neutralizing
      antibodies during an adaptive immune response. Currently there are no recombinant
      antibodies capable of binding gD epitopes for use in treating BoHV-1 infection.
      In this study, a bovine scFv gene derived from a hybridoma secreting monoclonal
      antibodies (McAbs) against the amino acid motif MEESKGYEPP of gD was expressed in
      E. coli. Molecular modeling, western blot and ELISA analysis showed that this
      scFv had a high affinity for BoHV-1 gD, with a Kd of 161.2 +/- 37.58 nM and for
      whole BoHV-1 virus, with a Kd of 67.44 +/- 16.99 nM. In addition, this scFv
      displayed a high affinity for BoHV-1 antigen in an ELISA and competed with BoHV-1
      anti-serum in a competitive ELISA. Immunofluorescence assay (IFA) and laser
      confocal microscopy showed that this scFv could efficiently bind to and be
      internalized by BoHV-1 infected Madin-Darby bovine kidney (MDBK) cells.
      Importantly, this scFv was shown to inhibit BoHV-1 infectivity and to reduce the
      number of viral plaques by blocking viral attachment to MDBK cells. Our study
      suggests that this bovine single-chain antibody could be developed for use as a
      diagnostic and therapeutic agent against BoHV-1 infection in cattle.

PMID- 29063174
TI  - Effects of different carbon sources on enhanced biological phosphorus removal and
      "Candidatus Accumulibacter" community composition under continuous aerobic
      condition.
AB  - Previous studies have shown that enhanced biological phosphorus removal (EBPR)
      performance under continuous aerobic conditions always eventually deteriorates;
      however, the speed at which this happens depends on the carbon source supplied.
      The published data suggest that propionate is a better carbon source than acetate
      is for maintaining operational stability, although it is not clear why. A lab
      scale sequencing batch reactor was run initially under conventional
      anaerobic/aerobic conditions with either acetate or propionate as the carbon
      source. Chemical and microbiological analyses revealed that both sources
      performed as expected for such systems. When continuous aerobic conditions were
      imposed on both these established communities, marked shifts of the "Candidatus
      Accumulibacter" clades were recorded for both carbon sources. Here, we discuss
      whether this shift could explain the prolonged EBPR stability observed with
      propionate.

PMID- 29063176
TI  - Evaluation of protein phosphorylation in bull sperm during their maturation in
      the epididymis.
AB  - Phosphorylation, or dephosphorylation, is one of the most frequent post
      translational modifications regulating protein-protein activity in eukaryotic
      cells. Whereas mature spermatozoa (as specialized cells) are transcriptionally
      inactive and do not synthesize new proteins, phosphorylation of sperm proteins is
      very important for the regulation of the sperm function. Although the post
      testicular maturation of spermatozoa is a process common to all mammals,
      comparative studies showed significant differences in sperm surface proteins and
      the mechanisms of protein modification during the epididymal maturation. In our
      study, the evaluation of tyrosine phosphorylation, represented by the fluorescent
      patterns of used anti-phosphotyrosine antibodies (P-Tyr-01 and 4G10), in
      spermatozoa isolated from different regions of the epididymis - caput, corpus and
      cauda - was performed. Although in general both antibodies detected almost the
      same reaction patterns, we observed some dissimilarity associated with the
      binding specificity of the antibodies and also the segment-dependent manner of
      phosphorylated protein localization. These data were filled up by
      immunohistochemical analysis of testes and epididymides cryosections.
      Additionally, our phosphoproteomic study focused on evaluation of the changes in
      the pattern of tyrosine-phosphorylated proteins during the post-testicular
      maturation of bull spermatozoa (PY20 antibody). To summarize the results, an
      increasing trend of tyrosine phosphorylation of proteins during the maturation of
      bull sperm in the epididymis was consistently observed in all the
      methods/experiments.

PMID- 29063177
TI  - Approach to Richter transformation of chronic lymphocytic leukemia in the era of
      novel therapies.
AB  - Chronic lymphocytic leukemia (CLL) has a highly variable clinical course. About 2
      10% of CLL patients develop aggressive histological transformation, most commonly
      to diffuse large B cell lymphoma (DLBCL), historically called Richter
      transformation (RT). Clinical features suggestive of RT include elevated LDH and
      non-specific symptoms such as fever, weight loss, and lymphadenopathy. 18
      fluorodeoxyglucose (18-FDG) uptake is increased on PET scan (standardized uptake
      value max most commonly >= 10). PET/CT study can identify optimal site for
      excisional biopsy, which is the gold standard for RT diagnosis, as well as aid in
      disease staging and prognostication. In addition to clinical prognostic features
      such lactate dehydrogenase level, platelet count, and performance status,
      important predictors of poor outcome in RT are TP53 disruption and clonal
      relationship of DLBCL to underlying CLL. Chemoimmunotherapy constitutes the
      standard treatment for RT, followed by stem cell transplant (SCT) in eligible
      patients. However, the majority of patients do not proceed to allogeneic SCT,
      either due to inadequate disease control with initial therapy, poor performance
      status, or lack of donor availability. Overall outcome is dismal. Some novel
      agents under investigation, particularly PD-1 inhibitors, are showing clinical
      activity in Phase I and II trials. An ongoing incidence of RT has been noted in
      studies of previously treated patients receiving targeted therapies such as
      ibrutinib and venetoclax; the frequency of RT in patients initially treated with
      novel agents rather than chemoimmunotherapy will be important to determine with
      longer follow-up. This review focuses on the development, clinicopathologic
      features, and treatment of RT in the context of novel therapies.

PMID- 29063178
TI  - Epstein-Barr virus positive diffuse large B cell lymphoma with G17V RHOA mutation
      arising from peripheral T cell lymphoma, not otherwise specified.

PMID- 29063179
TI  - Complete response of age-related Epstein-Barr virus-associated polymorphic nodal
      lymphoproliferative disease of plasmacytic type to low-dose lenalidomide.

PMID- 29063175
TI  - Convergent pathways in Parkinson's disease.
AB  - Preferential degeneration of dopamine neurons (DAn) in the midbrain represents
      the principal hallmark of Parkinson's disease (PD). It has been hypothesized that
      major contributors to DAn vulnerability lie in their unique cellular physiology
      and architecture, which make them particularly susceptible to stress factors.
      Here, we report a concise overview of some of the cell mechanisms that may
      exacerbate DAn sensitivity and loss in PD. In particular, we highlight how
      defective protein sorting and clearance, endoplasmic reticulum stress, calcium
      dyshomeostasis and intracellular trafficking converge to contribute
      synergistically to neuronal dysfunction in PD pathogenesis.

PMID- 29063180
TI  - Serum lipid feature and potential biomarkers of lethal ventricular
      tachyarrhythmia (LVTA) induced by myocardial ion channel diseases: a rat model
      study.
AB  - To determine the cause of death in myocardial ion channel diseases (MICD)-induced
      sudden cardiac death (SCD) cases is a difficulty in forensic identification
      practices. The majority of MICD-induced SCD cases would experience lethal
      ventricular tachyarrhythmia (LVTA) before deaths; thus, confirming the occurrence
      of LVTA in bodies can offer a key evidence to identify these cases. Several
      lipids in the myocardia were found disturbed after LVTA; yet, whether serum
      lipidome would be disrupted by LVTA is not clear. Therefore, we aimed to screen
      lipid feature and related diagnostic markers of LVTA in serum here. An aconitine
      induced LVTA-SCD rat model was produced. Blood samples before LVTA and
      immediately after LVTA were retrieved and related serum specimens were used for
      ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based
      lipidomics analyses. On the basis of the defined differential lipids, a lipid
      related metabolic pathway network was constructed and potential biomarkers were
      screened. Twelve aconitine-induced LVTA rats were produced. Totally, 188 lipids
      in serum were disrupted during the LVTA-SCD process, which belong to 11 lipid
      classes. Most of the differential lipids were correlated, suggesting that they
      were interacted and that the changes were holistic during LVTA process. Ten lipid
      pathways were activated during LVTA process; the main lipid classes involved in
      these pathways were ceramide, sphingomyelin, phosphatidylcholine,
      phosphatidylethanolamine, and phosphatidylserine. Phosphatidylcholine O-40:4,
      sphingomyelin d46:5, and phosphatidylethanolamine 40:4 were tested as potential
      diagnostic markers of LVTA-SCD event in serum. The current results indicate a
      substantial change in serum lipidome after LVTA-SCD; lipidomics holds promise to
      identify MICD-induced SCDs in forensic practices.

PMID- 29063181
TI  - Correction to: An analysis of the kinetics of molecular response during the first
      trimester of treatment with nilotinib in newly diagnosed chronic myeloid leukemia
      patients in chronic phase.
AB  - Correction to: J Cancer Res Clin Oncol (2017) 143:2059-2066 DOI 10.1007/s00432
      017-2445-z.

PMID- 29063182
TI  - Correction to: Predictors of outcomes after arthroscopic transosseous equivalent
      rotator cuff repair in 155 cases: a propensity score weighted analysis of knotted
      and knotless self-reinforcing repair techniques at a minimum of 2 years.
AB  - The author claims that his name is wrongly listed on PubMed. It seems, that first
      and last name have been mixed up. Correct first name is: J. Christoph (on PubMed:
      J.).

PMID- 29063183
TI  - Diffuse midline gliomas with subclonal H3F3A K27M mutation and mosaic H3.3 K27M
      mutant protein expression.

PMID- 29063184
TI  - Three-dimensional navigation-guided percutaneous screw fixation for nondisplaced
      and displaced pelvi-acetabular fractures in a major trauma centre.
AB  - BACKGROUND: Navigation assisted minimally invasive percutaneous screw fixation
      (MIS) for pelvi-acetabular fracture was recently advocated. METHODS: We report 38
      consecutive cases of pelvi-acetabular fractures treated with 3D navigation-guided
      MIS from 2015 to 2016. Ohe hundred and forty-three screws were inserted (59
      sacroiliac, 45 retrograde anterior column, 34 supra-acetabular, three antegrade
      posterior-column and two subcristal). Navigation planning was mainly performed
      pre-operatively. RESULTS: The mean operative blood loss and time was 179 ml and
      141 mins, respectively. The distance (deviation) between the planned and executed
      screw entry and tip measured by the navigation computer were 1.91 and 1.94 mm,
      respectively. There were no immediate or early surgical complications. Patients
      were followed for at least 6 month; 79% had fracture healing at 4.3 months on
      average, and 53% walked unaided by the six month follow-up. The average visual
      analogue scale for pain was 2.69. CONCLUSION: We believe 3D navigation-guided MIS
      is a safe and effective surgical alternative in most pelvi-acetabular fractures.

PMID- 29063185
TI  - Post-transcriptional silencing of chalcone synthase is involved in phenotypic
      lability in petals and leaves of bicolor dahlia (Dahlia variabilis) 'Yuino'.
AB  - MAIN CONCLUSION: Post-transcriptional gene silencing (PTGS) of a chalcone
      synthase ( DvCHS2 ) occurred in the white part of bicolor petals and flavonoid
      poor leaves; however, it did not in red petals and flavonoid-rich leaves. Petal
      color lability is a prominent feature of bicolor dahlia cultivars, and causes
      plants to produce not only original bicolor petals with colored bases and pure
      white tips, but also frequently single-colored petals without white tips. In this
      study, we analysed the molecular mechanisms that are associated with petal color
      lability using the red-white bicolor cultivar 'Yuino'. Red single-colored petals
      lose their white tips as a result of recover of flavonoid biosynthesis. Among
      flavonoid biosynthetic genes including four chalcone synthase (CHS)-like genes
      (DvCHS1, DvCHS2, DvCHS3, and DvCHS4), DvCHS1 and DvCHS2 had significantly lower
      expression levels in the white part of bicolor petals than in red petals, while
      DvCHS3, DvCHS4, and other flavonoid biosynthetic genes had almost the same
      expression levels. Small RNAs from the white part of a bicolor petal were mapped
      onto DvCHS1 and DvCHS2, while small RNAs from a red single-colored petal were not
      mapped onto any of the four CHS genes. A relationship between petal color and
      leaf flavonoid accumulation has previously been demonstrated, whereby red petal
      producing plants accumulate flavonoids in their leaves, while bicolor petal
      producing plants tend not to. The expression level of DvCHS2 was down-regulated
      in flavonoid-poor leaves and small RNAs from flavonoid-poor leaves were mapped
      onto DvCHS2, suggesting that the down-regulation of DvCHS2 in flavonoid-poor
      leaves occurs post-transcriptionally. Genomic analysis also suggested that DvCHS2
      is the key gene involved in bicolor formation. Together, these results suggest
      that post-transcriptional gene silencing of DvCHS2 plays a key role in phenotypic
      lability in this bicolor dahlia.

PMID- 29063187
TI  - Composite poplars: a novel tool for ectomycorrhizal research.
AB  - KEY MESSAGE: Composite poplars were used for ectomycorrhiza formation.
      Structurally normal mycorrhizas of transgenic roots revealed better fungal sugar
      support. Targeting fluorescent proteins to peroxisomes allowed easy in planta
      visualization of successful transformation. A bottle neck in ectomycorrhizal
      research is the time demand for generation of transgenic plants. An alternative
      strategy for such root-centered research might be the formation of the so-called
      composite plants, where transgenic roots are formed by non-transgenic shoots. We
      have developed an Agrobacterium rhizogenes-mediated root transformation protocol
      using axenic Populus tremula * tremuloides and P. tremula * alba cuttings. When
      comparing four different bacterial strains, A. rhizogenes K599 turned out to be
      the most suitable for poplar transformation. Transgenic roots revealed only minor
      hairy root phenotype when plants were grown on agar plates with synthetic growth
      medium in the absence of a sugar source. When using different ectomycorrhizal
      fungi, formation of ectomycorrhizas by transgenic roots of composite poplars was
      not affected and mycorrhizas were anatomically indistinguishable from mycorrhizas
      of non-transgenic roots. Elevated trehalose content and marker gene expression,
      however, pointed towards somewhat better fungal carbon nutrition in
      ectomycorrhizas of transgenic compared to non-transgenic roots. Cell wall
      autofluorescence of poplar fine roots is an issue that can limit the use of
      fluorescent proteins as visual markers for in planta analysis, especially after
      ectomycorrhiza formation. By targeting marker proteins to peroxisomes, sensitive
      fluorescence detection, easily distinguishable from cell wall autofluorescence,
      was obtained for both poplar fine roots and ectomycorrhizas.

PMID- 29063186
TI  - Effects of supplementation with rice husk powder and rice bran on inflammatory
      factors in overweight and obese adults following an energy-restricted diet: a
      randomized controlled trial.
AB  - PURPOSE: Overweight and obesity are major public health concerns worldwide which
      are associated with a low-grade chronic inflammation. Dietary fiber as an
      important component of diet could be effective in controlling weight and
      inflammatory factors. The present study aimed to compare the effects of rice husk
      powder and rice bran on inflammatory factors along with an energy-restricted diet
      in overweight and obese adults. METHODS: In this randomized trial, 105 eligible
      individuals were assigned to one of the three energy-restricted diet groups
      receiving; rice bran (n = 35), rice husk powder (n = 35), and control group (n =
      35) for 12 weeks. Demographic data, dietary intake, anthropometric indices and
      inflammatory factors (serum levels of IL-6 and hs-CRP) were measured at baseline
      and at the end of the study. RESULTS: Weight, BMI and waist circumference reduced
      significantly in all groups after 12 weeks of study (P < 0.01 for all). However,
      pre- and post-measure differences between groups were not significant. Moreover,
      serum levels of hs-CRP and IL-6 were not significantly different between
      participants in the rice bran or rice husk groups. However, the reduction in
      serum levels of hs-CRP in rice husk (mean change = - 0.14 +/- 0.05 ug/ml) and
      rice bran (mean change = - 0.13 +/- 0.03 ug/ml) was significantly higher when
      compared to the control group (mean change = - 0.03 +/- 0.02 ug/ml) (P < 0.05 for
      both groups). The same pattern was found when changes in IL-6 serum levels of
      participants in rice husk (mean change = - 0.48 +/- 0.11 pg/ml) and rice bran
      (mean change = - 0.57 +/- 0.13 pg/ml) groups were compared to the control group
      (mean change= - 0.19 +/- 0.07 pg/ml) (P < 0.05 for both groups). CONCLUSION: The
      results of this study showed positive effects of rice bran and rice husk powder
      supplementation, combined with an energy-restricted diet, on inflammatory markers
      among overweight and obese adults.

PMID- 29063189
TI  - Cellular subtype may predict survival outcomes in salivary adenoid cystic
      carcinoma patients-a single-institution experience.

PMID- 29063188
TI  - World-wide distributions of lactase persistence alleles and the complex effects
      of recombination and selection.
AB  - The genetic trait of lactase persistence (LP) is associated with at least five
      independent functional single nucleotide variants in a regulatory region about 14
      kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), 
      13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These
      alleles have been inferred to have spread recently and present-day frequencies
      have been attributed to positive selection for the ability of adult humans to
      digest lactose without risk of symptoms of lactose intolerance. One of the
      inferential approaches used to estimate the level of past selection has been to
      determine the extent of haplotype homozygosity (EHH) of the sequence surrounding
      the SNP of interest. We report here new data on the frequencies of the known LP
      alleles in the 'Old World' and their haplotype lineages. We examine and confirm
      EHH of each of the LP alleles in relation to their distinct lineages, but also
      show marked EHH for one of the older haplotypes that does not carry any of the
      five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a
      region of suppressed recombination that is detectable in families as well as in
      population data, and the results show how such suppression may have exaggerated
      haplotype-based measures of past selection.

PMID- 29063190
TI  - [Sudden loss of vision after cosmetic face treatment].

PMID- 29063191
TI  - Analysis of a purely conductance-based stochastic nerve fibre model as applied to
      compound models of populations of human auditory nerve fibres used in cochlear
      implant simulations.
AB  - The study presents the application of a purely conductance-based stochastic nerve
      fibre model to human auditory nerve fibres within finite element volume
      conduction models of a semi-generic head and user-specific cochleae. The
      stochastic, threshold and temporal characteristics of the human model are
      compared and successfully validated against physiological feline results with the
      application of a mono-polar, bi-phasic, cathodic first stimulus. Stochastic
      characteristics validated include: (i) the log(Relative Spread) versus log(fibre
      diameter) distribution for the discharge probability versus stimulus intensity
      plots and (ii) the required exponential membrane noise versus transmembrane
      voltage distribution. Intra-user, and to a lesser degree inter-user, comparisons
      are made with respect to threshold and dynamic range at short and long pulse
      widths for full versus degenerate single fibres as well as for populations of
      degenerate fibres of a single user having distributed and aligned somas with
      varying and equal diameters. Temporal characteristics validated through
      application of different stimulus pulse rates and different stimulus intensities
      include: (i) discharge rate, latency and latency standard deviation versus
      stimulus intensity, (ii) period histograms and (iii) interspike interval
      histograms. Although the stochastic population model does not reduce the modelled
      single deterministic fibre threshold, the simulated stochastic and temporal
      characteristics show that it could be used in future studies to model user
      specific temporally encoded information, which influences the speech perception
      of CI users.

PMID- 29063192
TI  - Spectrum of retinal abnormalities in renal transplant patients using chronic low
      dose steroids.
AB  - PURPOSE: To assess the ophthalmological characteristics of asymptomatic patients
      with a renal transplant on chronic low-dose steroids for at least the last 2
      years prior to examination. METHODS: Cross-sectional study. All patients
      underwent an extensive ophthalmological examination. RESULTS: Of the 37 included
      patients [25 male, 12 female; 59 +/- 11 years (range, 38-77 years)]
      ophthalmological phenotyping revealed abnormalities in 22 patients (59%).
      Findings characteristic for (subclinical) central serous chorioretinopathy were
      detected in ten patients (27%), including two patients with serous subretinal
      fluid in the macula. An epiretinal membrane of the macula was present in six
      patients (16%). Mean subfoveal choroidal thickness was significantly increased in
      patients with ophthalmological abnormalities, in comparison with patients without
      abnormalities. CONCLUSIONS: Retinal abnormalities are common in the majority of
      renal transplant patients using chronic low-dose steroids. These retinal changes
      may be associated with the renal disease and/or the effect of chronic steroid use
      on the choroid and retina.

PMID- 29063193
TI  - Vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary
      arteries in vitro and increased optic disc blood flow in vivo.
AB  - PURPOSE: This study aimed to clarify the vasodilatory effect of L-arginine on
      isolated rabbit and human posterior ciliary arteries (PCAs) and to investigate
      changes in optic disc blood flow after an infusion of L-arginine in vivo.
      METHODS: Vascular ring segments were mounted on a double myograph system. After
      obtaining maximal contraction following administration of high-K solution, L
      arginine was administrated. Six volunteers received an intravenous drip infusion
      of 100 ml of L-arginine or saline. Changes in optic disc blood flow were measured
      by laser speckle flowgraphy. RESULTS: L-arginine relaxed high-K solution-induced
      contracted rabbit PCAs. Carboxy-PTIO (nitric oxide scavenger) and L-NAME (nitric
      oxide synthase inhibitor) inhibited L-arginine-induced relaxation in rabbit PCAs.
      After removal of the endothelium of the rabbit PCAs, L-arginine still relaxed
      rabbit PCAs. L-arginine relaxed human PCAs, despite the lack of nitric oxide
      production. In the L-arginine infusion group, the mean blur rate was
      significantly greater than that of the control group in vivo. CONCLUSION: L
      arginine has both nitric oxide-dependent and independent vasodilatory effect on
      high K- induced contractions in isolated rabbit and human PCAs. L-arginine
      increased optic disc blood flow in vivo.

PMID- 29063194
TI  - Avian haemosporidian detection across source materials: prevalence and genetic
      diversity.
AB  - Avian haemosporidians make up one of the most widely distributed and diverse
      vector borne parasite systems, found nearly worldwide in tropical and temperate
      areas. Despite the clear relationship between avian host fitness measures and
      infection, few studies have addressed the importance of source material selection
      when assessing these relationships. We show that source material, here blood and
      pectoral muscle, do not yield equivalent results when assessing prevalence and
      genetic diversity of haemosporidian genera. We find higher prevalence and genetic
      diversity are recovered from blood versus pectoral muscle for Haemoproteus.
      Contrastingly, we find that a higher prevalence of Plasmodium is detected from
      pectoral muscle, while higher genetic diversity is recovered from blood. Our
      results indicate that source material may bias parasite detection and be an
      important factor in study design, which is not only related to parasite
      infection, but by extension to the ecology and fitness of avian hosts.

PMID- 29063195
TI  - Guppies (Poecilia reticulata) introducing an alien parasite, Camallanus cotti
      (Nematoda: Camallanidae) to Africa, the first report.
AB  - Introduced alien fish species and their associated parasites may result in a
      serious threat to indigenous biodiversity. Furthermore, this may have negative
      impacts on cultured fish as well as on native parasitic fauna. In the present
      study, the invasive Asian nematode, Camallanus cotti Fujita, 1927 (Nematoda:
      Camallanidae), is reported from the guppy (Poecilia reticulata) for the first
      time in Africa. This parasite is assumed to be introduced into Africa along with
      the introduction of exotic poeciliid fishes, which are known to be the most
      common hosts of C. cotti in ornamental fish industry worldwide.The presence of
      this parasite in both aquarium-cultured fish as well as fish from natural
      waterbodies is evidence of the introduction of the alien organisms due to
      insufficient prophylactic veterinary control during transfer of non-native hosts
      between countries and the spread of them by the anthropogenic introduction to
      natural systems.

PMID- 29063197
TI  - Emission of greenhouse gases and soil carbon sequestration in a riparian marsh
      wetland in central Ohio.
AB  - Wetlands are a C sink, but they also account for a large natural source of
      greenhouse gases (GHG), particularly methane (CH4). Soils of wetlands play an
      important role in alleviating the global climate change regardless of the
      emission of CH4. However, there are uncertainties about the amount of C stored
      and emitted from wetlands because of the site specific factors. Therefore, the
      present study was conducted in a temperate riverine flow-through wetland, part of
      which was covered with emerging macrophyte Typhus latifolia in central Ohio, USA,
      with the objective to assess emissions of GHGs (CH4, CO2, N2O) and measure C and
      nitrogen (N) stocks in wetland soil in comparison to a reference upland site. The
      data revealed that CH4 emission from the open and vegetated wetland ranged from
      1.03-0.51 Mg C/ha/y and that of CO2 varied from 1.26-1.51 Mg C/ha/y. In
      comparison, CH4 emission from reference upland site was negligible (0.01 Mg
      C/ha/y), but CO2 emission was much higher (3.24 Mg C/ha/y). The stock of C in
      wetland soil was 85 to 125 Mg C/ha up to 0.3 m depth. The average rate of
      emission was 2.15 Mg C/ha/y, but the rate of sequestration was calculated as 5.55
      Mg C/ha/y. Thus, the wetland was actually a C sink. Emission of N2O was slightly
      higher in vegetated wetland (0.153 mg N2O-N/m2/h) than the open wetland and the
      reference site (0.129 mg N2O-N/m2/h). Effect of temperature on emission of GHGs
      from the systems was also studied.

PMID- 29063196
TI  - A newly synthesized nickel chelate can selectively target and overcome multidrug
      resistance in cancer through redox imbalance both in vivo and in vitro.
AB  - Induction of undesired toxicity and emergence of multidrug resistance (MDR) are
      the major obstacles for cancer treatment. Moreover, aggressive cancers are less
      sensitive towards existing chemotherapeutics. Therefore, selective targeting of
      cancers without inducing undesired side effects and designing proper strategies
      to overcome MDR has utmost importance in modern chemotherapy. Previously we
      revealed the anticancer properties of some transition metal chelates of Schiff
      base, but the effectiveness of nickel complex is still unrevealed. Herein, we
      synthesized and characterized a Schiff base nickel chelate, nickel-(II) N-(2
      hydroxyacetophenone) glycinate (NiNG), through different spectroscopic means.
      NiNG proves to be a broad spectrum anticancer agent with considerable efficacy to
      overcome MDR in cancer. Antiproliferative effects of NiNG was evaluated using
      drug-resistant (CEM/ADR5000; NIH-MDR-G185; EAC/Dox), drug-sensitive aggressive
      (Hct116; CCRF-CEM; EAC/S) and normal (NIH-3T3) cells that reveal the selective
      nature of NiNG towards drug resistant and sensitive cancer cells without inducing
      any significant toxicity in normal cells. Moreover, NiNG involves reactive oxygen
      species (ROS)-mediated redox imbalance for induction of caspase 3-dependent
      apoptosis in aggressive drug-sensitive Hct116 and drug-resistant NIH-MDR-G185
      cells through disruption of mitochondrial membrane potential. Moreover,
      intraperitoneal (i.p.) application of NiNG at non-toxic doses caused significant
      increase in the life-span of Swiss albino mice bearing sensitive and doxorubicin
      resistant subline of Ehrlich ascites carcinoma cells. It is noteworthy that, in
      vitro NiNG can only overcome P-glycoprotein-mediated MDR while in vivo NiNG can
      overcome MRP1-mediated MDR in cancer. Therefore, NiNG has therapeutic potential
      to target and overcome MDR in cancer.

PMID- 29063198
TI  - Dental fluorosis, nutritional status, kidney damage, and thyroid function along
      with bone metabolic indicators in school-going children living in fluoride
      affected hilly areas of Doda district, Jammu and Kashmir, India.
AB  - A case-control study was undertaken among the school children aged 8-15 years to
      know the presence and severity of dental fluorosis, nutrition and kidney status,
      and thyroid function along with bone metabolic indicators in Doda district
      situated at high altitude where drinking water was contaminated and heat stress.
      This study included 824 participants with an age of 8-15 years. The results of
      the study reviled that dental fluorosis was significantly higher in affected than
      control area children. Urinary fluoride was significantly higher (p < 0.05) in
      affected children as compared to the control area school children. Nutritional
      status of affected children was lower than control area children. The chronic
      kidney damage (CKD) was higher in affected than control school children. Thyroid
      function was affected more in affected than control area schools. Serum
      creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH)2 vitamin
      D, and osteocalcin were significantly higher in affected school children (p <
      0.05) as compared to control school children, whereas there was no significant
      difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among
      the two groups. There was a significant decrease in thyroid-stimulating hormone
      (TSH) in the affected area school children compared to control. In conclusion,
      fluorotic area school children were more affected with dental fluorosis, kidney
      damage, along and some bone indicators as compared to control school children.

PMID- 29063199
TI  - Urbanization-mediated context dependence in the effect of floral neighborhood on
      pollinator visitation.
AB  - Context dependence in ecological interactions is widespread, but our ability to
      predict how environmental variation will mediate the effects of a given
      interaction remains poor. Co-flowering plants can influence visitation of shared
      pollinators to one another; the effect of these interactions varies with
      ecological context. While research has investigated the effect of local biotic
      conditions on such interactions, little is known about how land use change,
      specifically urbanization, affects them. I tested how the interaction of
      urbanization and neighborhood floral density (NFD) and richness affected
      pollinator visitation rates to two crop species, cucumber and sunflower by
      placing experimental arrays of each species in paired high- (garden) and low-
      (lawn) floral density neighborhoods along an urban-to-rural gradient. Pollinator
      visitation to flowers was monitored over 2 years, as was NFD and richness. The
      two plant species showed contrasting responses to both urbanization and floral
      neighborhood density, with only cucumber experiencing context dependence in the
      effect of floral neighborhood. These contrasting responses to urbanization and
      floral neighborhood are likely due to differences between species in floral
      visitor community composition. Plants grown in gardens experienced higher
      pollinator visitation regardless of floral neighborhood. This study highlights
      the need for better understanding of genus- or species-specific pollinator
      responses to urbanization to predict the effect of urbanization on plant
      pollinator interactions.

PMID- 29063201
TI  - A population-based study of the relationship between perinatal depressive
      symptoms and breastfeeding: a cross-lagged panel study.
AB  - Studies suggest that perinatal depression and breastfeeding co-vary, but
      determining the relationship between breastfeeding and perinatal depression has
      proved challenging. A bidirectional association has been suggested, implying that
      depression may impact on breastfeeding and that breastfeeding might influence
      depressive symptoms. The present study aimed to contribute to the understanding
      of the relationship between perinatal depression and breastfeeding in a
      population-based sample where we used structural equation modeling (SEM)
      techniques to investigate cross-lagged and autoregressive effects as well as
      concurrent associations. The present study was part of a large-scale Norwegian
      prospective study. Nurses and midwives at nine well-baby clinics recruited
      participants. All the well-baby clinics had implemented the Edinburgh method,
      which combines the use of the Edinburgh Postnatal Depression Scale (EPDS) with an
      immediate follow-up conversation. Completed EPDS forms were recorded, as well as
      the mothers' reports of breastfeeding behaviors. Depressive symptoms measured
      prenatally during the last trimester, at 4 and 6 months postpartum did not
      predict breastfeeding behavior at 4, 6, or 12 months postpartum, respectively.
      Furthermore, breastfeeding at 4 and 6 months postpartum did not predict
      depressive symptomatology at 6 or 12 months postpartum. There were no significant
      concurrent associations between breastfeeding and depressive symptoms at 4, 6, or
      12 months postpartum. Depressive symptoms predicted subsequent depressive
      symptoms and breastfeeding predicted subsequent breastfeeding. There was no
      evidence of a relationship between depressive symptoms and breastfeeding.
      Potential explanations and implications are discussed.

PMID- 29063200
TI  - Insights on dispersal and recruitment paradigms: sex- and age-dependent
      variations in a nomadic breeder.
AB  - Sex- and age-dependence in recruitment and dispersal are often explained by costs
      arising from competition for holding a breeding territory over the years-a
      typical feature of species living in stable habitats. For instance, long-lived
      birds with male territoriality often exhibit large variation in recruitment age
      and higher dispersal in females and young individuals. As a corollary, we
      expected that species with ephemeral habitat suitability, and hence nomadic
      breeding, would show weak age- and sex-dependence in dispersal and low variation
      in recruitment age, because territory ownership is not maintained over the years.
      In addition, the higher cost of reproduction in females might not be
      (over)compensated for by costs of territoriality in males. Accordingly, females
      would recruit later than males. We explored these variations using multievent
      capture-recapture models over 13 years, 3479 (2392 sexed) slender-billed gulls
      (Chroicocephalus genei) and 45 colony sites along the French Mediterranean coast.
      As expected, variability in recruitment age was low with males recruiting earlier
      than females. Nonetheless, dispersal in and out of the study area decreased with
      age and was slightly higher in males than in females. Decreased dispersal with
      age might result from foraging benefits associated with increased spatial
      familiarity. Higher dispersal in males might be explained by a male-biased sex
      ratio or higher philopatry benefits in females (arising from their higher cost of
      reproduction). Sex- and age-dependent dispersal and recruitment may thus occur in
      the absence of year-to-year breeding territory ownership, which stresses the
      importance of considering other processes in shaping recruitment and dispersal
      patterns.

PMID- 29063202
TI  - Vitex agnus castus for premenstrual syndrome and premenstrual dysphoric disorder:
      a systematic review.
AB  - The objective of this study was to evaluate whether Vitex agnus castus is a safe
      and effective treatment for PMS and premenstrual dysphoric disorder (PMDD) and to
      discuss the implications of these findings for clinical practice. A systematic
      review of literature was conducted using PubMed and Scielo databases. The
      inclusion criteria were randomized controlled trials (RCT) using V. agnus castus
      in individuals with PMS or PMDD that compared this intervention with placebo or
      an active comparator and included a description of blinding and
      dropouts/withdrawals. The search was conducted by two independent investigators
      who reached consensus on the included trials. A total of eight RCTs were included
      in this study. Most studies focused on PMS, and the diagnostic criteria of PMS
      and PMDD changed over the years. Three different preparations of V. agnus castus
      (VAC) were tested, and there was significant variability in the measurement of
      treatment outcomes between the studies. Nevertheless, all eight studies were
      positive for VAC in the treatment of PMS or PMDD and VAC was overall well
      tolerated. Main limitations were differences in definition of diagnostic
      criteria, the instruments used as main outcome measures, and different
      preparations of VAC extracts limit the comparison of results between studies. In
      conclusion, the RCTs using VAC for treatment of PMS/PMDD suggested that the VAC
      extract is a safe and efficacious alternative to be considered for the treatment
      of PMS/PMDD symptoms.

PMID- 29063204
TI  - Catalytic coupling reaction mechanism of 4-nitrobenzenethiol on silver clusters:
      a density functional theoretical study.
AB  - The catalytic coupling reaction mechanism of the transformation from 4
      nitrobenzenethiol (4-NBT) to 4,4'-dimercaptoazobenzene (4,4'-DMAB) on a silver
      cluster was studied by density functional theory. Reactants, intermediates,
      transition states and products were optimized with the B3LYP method using the 6
      311 + G(d,p) basis set (Ag using the pseudo potential basis set of LanL2DZ).
      Transition states and intermediates were confirmed by the corresponding vibration
      analysis and intrinsic reaction coordinates (IRC). Consistent with literature
      reports, the key point of the transformation from 4-NBT absorbed on the surface
      of Ag5 clusters to 4,4'-DMAB is the elimination of two O atoms on the amino
      group. Meanwhile, the catalytic coupling reaction of 4-nitrobenzenethiol on a
      silver cluster is easy to carry out under irradiation. The possibility of "inter
      system channeling" (ISC) between different potential energy surfaces in the
      coupling reaction of 4-NBT is further discussed. The irradiation has an auxiliary
      catalytic effect on the coupling reaction. Our research results can explain the
      observed experimental phenomena. Graphical abstract Catalytic coupling reaction
      mechanism of the transformation from 4-nitrothiophenol (4-NBT) to 4,4'
      dimercaptoazobenzene (4,4'-DMAB) on silver clusters studied by density functional
      theory.

PMID- 29063203
TI  - Cortical dysplasia and autistic trait severity in children with Tuberous
      Sclerosis Complex: a clinical epidemiological study.
AB  - Tuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism
      spectrum disorders (ASD). Little is known about the relation between cortical
      dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism
      Diagnostic Observation Scale), tuber and radial migration line (RML) count and
      location, and cognitive functioning in 52 children with TSC and performed
      regression and mediation analyses. Tuber and RML count were strongly positively
      related to ASD severity. However, when correcting for cognitive functioning, the
      majority of associations became insignificant and only total tuber count remained
      associated to the severity of restricted/repetitive behaviors. Occipital RML
      count remained associated with overall ASD severity, and social
      communication/interaction deficit severity specifically. This study shows the
      important explanatory role of cognitive functioning in the association between
      cortical dysplasia and ASD severity, and the relevance of separately studying the
      two ASD subdomains.

PMID- 29063205
TI  - Steered molecular dynamics simulation of the binding of the bovine auxilin J
      domain to the Hsc70 nucleotide-binding domain.
AB  - The Hsp70 and Hsp40 chaperone machine plays critical roles in protein folding,
      membrane translocation, and protein degradation by binding and releasing protein
      substrates in a process that utilizes ATP. The activities of the Hsp70 family of
      chaperones are recruited and stimulated by the J domains of Hsp40 chaperones.
      However, structural information on the Hsp40-Hsp70 complex is lacking, and the
      molecular details of this interaction are yet to be elucidated. Here we used
      steered molecular dynamics (SMD) simulations to investigate the molecular
      interactions that occur during the dissociation of the auxilin J domain from the
      Hsc70 nucleotide-binding domain (NBD). The changes in energy observed during the
      SMD simulation suggest that electrostatic interactions are the dominant type of
      interaction. Additionally, we found that Hsp70 mainly interacts with auxilin
      through the surface residues Tyr866, Arg867, and Lys868 of helix II, His874,
      Asp876, Lys877, Thr879, and Gln881 of the HPD loop, and Phe891, Asn895, Asp896,
      and Asn903 of helix III. The conservative residues Tyr866, Arg867, Lys868,
      His874, Asp876, Lys877, and Phe891 were also found in a previous study to be
      indispensable to the catalytic activity of the DnaJ J domain and the binding of
      it with the NBD of DnaK. The in silico identification of the importance of
      auxilin residues Asn895, Asp896, and Asn903 agrees with previous mutagenesis and
      NMR data suggesting that helix III of the J domain of the T antigen interacts
      with Hsp70. Furthermore, our data indicate that Thr879 and Gln881 from the HPD
      loop are also important as they mediate the interaction between the bovine
      auxilin J domain and Hsc70.

PMID- 29063206
TI  - Plastic pollution in freshwater ecosystems: macro-, meso-, and microplastic
      debris in a floodplain lake.
AB  - Plastic pollution is considered an important environmental problem by the United
      Nations Environment Programme, and it is identified, alongside climate change, as
      an emerging issue that might affect biological diversity and human health.
      However, despite research efforts investigating plastics in oceans, relatively
      little studies have focused on freshwater systems. The aim of this study was to
      estimate the spatial distribution, types, and characteristics of macro-, meso-,
      and microplastic fragments in shoreline sediments of a freshwater lake. Food
      wrappers (mainly polypropylene and polystyrene), bags (high- and low-density
      polyethylene), bottles (polyethylene terephthalate), and disposable Styrofoam
      food containers (expanded polystyrene) were the dominant macroplastics recorded
      in this study. Contrary to other studies, herein macroplastic item surveys would
      not serve as surrogates for microplastic items. This is disadvantageous since
      macroplastic surveys are relatively easier to conduct. Otherwise, an average of
      25 mesoplastics (mainly expanded polystyrene) and 704 microplastic particles
      (diverse resins) were recorded per square meter in sandy sediments. Comparisons
      with other studies from freshwater and marine beaches indicated similar relevance
      of plastic contamination, demonstrating for the first time that plastic pollution
      is a serious problem in the Parana floodplain lakes. This study is also valuable
      from a social/educational point of view, since plastic waste has been ignored in
      the Parana catchment as a pollutant problem, and therefore, the outcome of the
      current study is a relevant contribution for decision makers.

PMID- 29063207
TI  - Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes.
AB  - PURPOSE OF REVIEW: This review summarizes the current knowledge on the
      relationship of physical activity, exercise, and cardiorespiratory fitness (CRF)
      with cardiovascular autonomic neuropathy (CAN) based on epidemiological,
      clinical, and interventional studies. RECENT FINDINGS: The prevalence of CAN
      increases with age and duration of diabetes. Further risk factors for CAN
      comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension,
      and the presence of diabetic complications. CAN has been also linked to reduced
      CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or
      oxidative capacity at the anaerobic threshold) are associated with cardiac
      autonomic function in patients recently diagnosed with type 1 or type 2 diabetes.
      Exercise interventions have shown that physical activity can increase cardiovagal
      activity and reduce sympathetic overactivity. In particular, long-term and
      regularly, but also supervised, performed endurance and high-intense and high
      volume exercise improves cardiac autonomic function in patients with type 2
      diabetes. By contrast, the evidence in those with type 1 diabetes and also in
      individuals with prediabetes or metabolic syndrome is weaker. Overall, the
      studies reviewed herein addressing the question whether favorably modulating the
      autonomic nervous system may improve CRF during exercise programs support the
      therapeutic concept to promote physical activity and to achieve physical fitness.
      However, high-quality exercise interventions, especially in type 1 diabetes and
      metabolic syndrome including prediabetes, are further required to better
      understand the relationship between physical activity, fitness, and cardiac
      autonomic function.

PMID- 29063208
TI  - Glucometrics and Insulinometrics.
AB  - PURPOSE OF REVIEW: Glucometrics is the systematic analysis of inpatient glucose
      data and is of key interest as hospitals strive to improve inpatient glycemic
      control. Insulinometrics is the systematic analysis and reporting of inpatient
      insulin therapy. This paper reviews some of the questions to be resolved before a
      national benchmarking process can be developed that will allow institutions to
      track and compare inpatient glucose control performance against established
      guidelines. RECENT FINDINGS: There remains a lack of standardization on how
      glucometircs should be measured and reported. Before hospitals can commit
      resources to compiling and extracting data, consensus must be reached on such
      questions as which measures to report, definitions of glycemic targets, and how
      data should be obtained. Examples are provided on how insulin administration can
      be measured and reported. Hospitals should begin assessment of glucometrics and
      insulinometrics. However, consensus and standardization must first occur to allow
      for a national benchmarking process.

PMID- 29063209
TI  - Interrelationship between iodine nutritional status of lactating mothers and
      their absolutely breast-fed infants in coastal districts of Gangetic West Bengal
      in India.
AB  - : Iodine nutritional status of 128 lactating mothers and their breast-fed infants
      (1-3 months) from iodine-replete villages during post-salt iodization period was
      evaluated. Mothers' urine, blood, and breast milk (BM) and infants' urine and
      blood were collected and analyzed for iodine and serum FT4 and TSH estimation.
      Mothers' and infants' age, parity, occupation, education, and household income
      were recorded. Median urinary iodine concentration (UIC) of infants was 250
      MUg/L, indicating their iodine intake was more than adequate. Mothers' median UIC
      was 185 MUg/L, indicating adequate iodine nutrition; however, 13.28% had mild to
      severe deficiency. Median breast milk iodine concentration (BMIC) was 230 MUg/L,
      which was more than their median UIC 185 MUg/L. In iodine-deficient mothers,
      positive correlation was found between mothers' and infants' serum FT4 and TSH
      levels, and negative correlation was found between mothers' and infants' serum
      FT4 and TSH levels in excessive iodine nutrition group. CONCLUSION: Iodine intake
      of breast-fed infants was at the limit of above requirement, and they are
      possibly at the risk of excess iodine intake. In iodine deficient and excessive
      iodine intake mothers, their infants' serum FT4 and TSH are independent on their
      iodine nutritional status but dependent on thyroid hormone profile of their
      mothers but differently. What is Known: * A median urinary iodine of 100 MUg/L is
      used to define adequate iodine intake of lactating mothers and children < 2
      years. However, adequate iodine intake in terms of urinary iodine of infants of
      age 1-3 months is not known. What is New: * Iodine intake of absolutely breast
      fed infants (1-3 months) was more than adequate, though their mother's intake was
      adequate as breast milk contains more iodine than urine. The infants of iodine
      deficient and excessive iodine intake mothers, infants' hormonal profile is
      independent of their iodine nutritional status but dependent on their mothers
      thyroid hormone profile.

PMID- 29063210
TI  - Late-onset sepsis due to urinary tract infection in very preterm neonates is not
      uncommon.
AB  - : Urinary tract infection (UTI) is a common cause of sepsis in infants. Premature
      infants hospitalized at a neonatal intensive care unit often have risk factors
      for infection. In this group, the risk of UTI is not clearly known, and
      guidelines for urine analysis are not unanimous. We aimed to identify the risk of
      UTI in premature infants with central lines, suspected of late-onset sepsis. We
      analyzed all 1402 infants admitted to our hospital between 2006 and 2014 with a
      gestational age less than 32 weeks. Six hundred sixty-two episodes of sepsis
      evaluations were found with an unknown source of infection based on clinical
      symptoms. In half of this group, urine analysis was performed identifying UTI in
      11.3% (24/212). In 13 of these infants (54%) with a UTI, infection was due to
      Candida albicans. In at least four episodes, the diagnosis and treatment would
      have been delayed if urine analysis had not been performed. CONCLUSION: Based on
      these findings, we conclude that in premature infants with central lines, urine
      analysis should be performed routinely when signs of infection occur beyond 72 h
      after birth. Urine collection should not be delayed and cultures should
      preferably be performed before the start of the antibiotic treatment. What is
      known: * In preterm infants, the presence of other risk factors for infection
      might make clinicians reluctant to obtain urine cultures during sepsis
      evaluation. * An internal survey demonstrated that there is no consensus within
      the NICUs in The Netherlands regarding urine analysis as part of LOS work-up.
      What is new: * The risk of UTI in the NICU population (11.3%) is comparable to
      term infants; therefore, urine analysis should be performed routinely when LOS is
      suspected. * Candida albicans was the most frequently (54%) detected pathogen
      causing UTI in this population.

PMID- 29063211
TI  - Physiopathology of Migraine: What Have We Learned from Functional Imaging?
AB  - PURPOSE OF REVIEW: This review aims to provide an overview of the most recent and
      significant functional neuroimaging studies which have clarified the complex
      mechanisms underlying migraine pathophysiology. RECENT FINDINGS: The recent data
      allow us to overcome the concept of a migraine generator suggesting that
      functional networks abnormalities may lead to changes in different brain area
      activities and consequent reduced migraine thresholds susceptibility, likely
      associated with higher migraine severity and burden. Although functional magnetic
      resonance imaging studies have allowed recognition of several migraine
      mechanisms, its pathophysiology is not completely understood and is still a
      matter of research. Nevertheless, in recent years, functional magnetic resonance
      imaging studies have allowed us to implement our knowledge of migraine
      pathophysiology. The pivotal role of both the brainstem and the hippocampus in
      the first phase of a migraine attack, the involvement of limbic pathway in the
      constitution of a migrainous pain network, the disrupted functional connectivity
      in cognitive brain networks, as well as the abnormal function of the visual
      network in patients with migraine with aura are the main milestones in migraine
      imaging achieved through functional imaging advances. We believe that further
      studies based on combined functional and structural techniques and the
      investigation of the different phases of migraine cycle may represent an
      efficient methodological approach for comprehensively looking into the migrainous
      brain secrets.

PMID- 29063214
TI  - Geisinger high-risk osteoporosis clinic (HiROC): 2013-2015 FLS performance
      analysis.
AB  - : Geisinger Health System (GHS) high-risk osteoporosis clinic (HiROC), which
      treats patients with low-trauma, fragility fractures, reports their 2013-2015
      performance measures in secondary fracture prevention. This fracture liaison
      service (FLS) pathway treats 75% of high-risk, drug eligible patients, compared
      to 13.8% in GHS primary care. This performance points to the need for more FLS
      programs throughout the world. INTRODUCTION: The purpose of this study is to
      analyze and report ongoing performance measures in outpatient and inpatient high
      risk osteoporosis clinic (HiROC) program designed for patients with low-trauma,
      fragility fractures. METHODS: Retrospective chart review of outpatient HiROC (511
      patients) and inpatient HiROC (1279 patients) performance from 2013 to 2015 is
      reported within Geisinger Health System (GHS). RESULTS: Similar to a prior
      report, we document that Geisinger's branded outpatient and inpatient HiROC
      pathways continue to function as an all-fracture FLS. Importantly, this analysis
      emphasizes the importance of FLS care that HiROC's treatment rate of 75% was
      markedly superior to GHS-PCP care of 13.8%. However, a large percentage of
      patients (37.8%) were lost to follow-up care. This led to the identification of
      multiple care gaps/barriers to ideal best practice. CONCLUSIONS: FLS programs use
      case finding strategies and address secondary fracture prevention. GHS HiROC's
      performance and initiation of drug therapy in this fracture patient population
      contrasts with GHS-PCP care's much lower rate of treatment, documenting the need
      for ongoing FLS care. Importantly, the results of this analysis have prompted the
      beginnings of GHS programmatic changes, designed to narrow the reported care gaps
      in this mature FLS.

PMID- 29063215
TI  - Were VCF patients at higher risk of mortality following the 2009 publication of
      the vertebroplasty "sham" trials?
AB  - : The 5-year period following 2009 saw a steep reduction in vertebral
      augmentation volume and was associated with elevated mortality risk in vertebral
      compression fracture (VCF) patients. The risk of mortality following a VCF
      diagnosis was 85.1% at 10 years and was found to be lower for balloon kyphoplasty
      (BKP) and vertebroplasty (VP) patients. INTRODUCTION: BKP and VP are associated
      with lower mortality risks than non-surgical management (NSM) of VCF. VP versus
      sham trials published in 2009 sparked controversy over its effectiveness, leading
      to diminished referral volumes. We hypothesized that lower BKP/VP utilization
      would lead to a greater mortality risk for VCF patients. METHODS: BKP/VP
      utilization was evaluated for VCF patients in the 100% US Medicare data set (2005
      2014). Survival and morbidity were analyzed by the Kaplan-Meier method and
      compared between NSM, BKP, and VP using Cox regression with adjustment by
      propensity score and various factors. RESULTS: The cohort included 261,756 BKP
      (12.6%) and 117,232 VP (5.6%) patients, comprising 20% of the VCF patient
      population in 2005, peaking at 24% in 2007-2008, and declining to 14% in 2014.
      The propensity-adjusted mortality risk for VCF patients was 4% (95% CI, 3-4%; p <
      0.001) greater in 2010-2014 versus 2005-2009. The 10-year risk of mortality for
      the overall cohort was 85.1%. BKP and VP cohorts had a 19% (95% CI, 19-19%; p <
      0.001) and 7% (95% CI, 7-8%; p < 0.001) lower propensity-adjusted 10-year
      mortality risk than the NSM cohort, respectively. The BKP cohort had a 13% (95%
      CI, 12-13%; p < 0.001) lower propensity-adjusted 10-year mortality risk than the
      VP cohort. CONCLUSIONS: Changes in treatment patterns following the 2009 VP
      publications led to fewer augmentation procedures. In turn, the 5-year period
      following 2009 was associated with elevated mortality risk in VCF patients. This
      provides insight into the implications of treatment pattern changes and
      associated mortality risks.

PMID- 29063213
TI  - High dairy protein intake is associated with greater bone strength parameters at
      the distal radius and tibia in older men: a cross-sectional study.
AB  - : Dairy protein but not plant protein was associated with bone strength of the
      radius and tibia in older men. These results are consistent with previous results
      in women and support similar findings related to fracture outcomes. Bone strength
      differences were largely due to thickness and area of the bone cortex.
      INTRODUCTION: Our objective was to determine the association of protein intake by
      source (dairy, non-dairy animal, plant) with bone strength and bone
      microarchitecture among older men. METHODS: We used data from 1016 men (mean 84.3
      years) who attended the Year 14 exam of the Osteoporotic Fractures in Men (MrOS)
      study, completed a food frequency questionnaire (500-5000 kcal/day), were not
      taking androgen or androgen agonists, and had high-resolution peripheral
      quantitative computed tomography (HR-pQCT) scans of the distal radius and distal
      or diaphyseal tibia. Protein was expressed as percentage of total energy intake
      (TEI); mean +/- SD for TEI = 1548 +/- 607 kcal/day and for total protein = 16.2
      +/- 2.9%TEI. We used linear regression with standardized HR-pQCT parameters as
      dependent variables and adjusted for age, limb length, center, education,
      race/ethnicity, marital status, smoking, alcohol intake, physical activity level,
      corticosteroids use, supplement use (calcium and vitamin D), and osteoporosis
      medications. RESULTS: Higher dairy protein intake was associated with higher
      estimated failure load at the distal radius and distal tibia [radius effect size
      = 0.17 (95% CI 0.07, 0.27), tibia effect size = 0.13 (95% CI 0.03, 0.23)], while
      higher non-dairy animal protein was associated with higher failure load at only
      the distal radius. Plant protein intake was not associated with failure load at
      any site. CONCLUSION: The association between protein intake and bone strength
      varied by source of protein. These results support a link between dairy protein
      intake and skeletal health, but an intervention study is needed to evaluate
      causality.

PMID- 29063218
TI  - 7th National Congress of the Italian Society of Colorectal Surgery : Rome,
      September 30-October 3, 2017 Presidents: Claudio Coco, Claudio Mattana, Carlo
      Ratto.

PMID- 29063216
TI  - Older men who sustain a hip fracture experience greater declines in bone mineral
      density at the contralateral hip than non-fractured comparators.
AB  - : Men experience declining bone mineral density (BMD) after hip fracture;
      however, changes attributable to fracture are unknown. This study evaluated the
      excess BMD decline attributable to hip fracture among older men. Older men with
      hip fracture experienced accelerated BMD declines and are at an increased risk of
      secondary fractures. INTRODUCTION: The objective was to determine whether bone
      mineral density (BMD) changes in men after hip fracture exceed that expected with
      aging. METHODS: Two cohorts were used: Baltimore Hip Studies 7th cohort (BHS-7)
      and Baltimore Men's Osteoporosis Study (MOST). BHS-7 recruited older adults (N =
      339) hospitalized for hip fracture; assessments occurred within 22 days of
      admission and at 2, 6, and 12 months follow-up. MOST enrolled age-eligible men (N
      = 694) from population-based listings; data were collected at a baseline visit
      and a second visit that occurred between 10 and 31 months later. The combined
      sample (n = 452) consisted of Caucasian men from BHS-7 (n = 89) and MOST (n =
      363) with >= 2 dual-energy X-ray absorptiometry scans and overlapping ranges of
      age, height, and weight. Mixed-effect models estimated rates of BMD change, and
      generalized linear models evaluated differences in annual bone loss at the total
      hip and femoral neck between cohorts. RESULTS: Adjusted changes in total hip and
      femoral neck BMD were - 4.16% (95% CI, - 4.87 to - 3.46%) and - 4.90% (95% CI, -
      5.88 to - 3.92%) in BHS-7 participants; - 1.57% (95% CI, - 2.19 to - 0.96%) and -
      0.99% (95% CI, - 1.88 to - 0.10%) in MOST participants; and statistically
      significant (P < 0.001) between-group differences in change were - 2.59% (95% CI,
      - 3.26 to - 1.91%) and - 3.91% (95% CI, - 4.83 to - 2.98%), respectively.
      CONCLUSION: Hip fracture in older men is associated with accelerated BMD declines
      at the non-fractured hip that are greater than those expected during aging, and
      pharmacological interventions in this population to prevent secondary fractures
      may be warranted.

PMID- 29063217
TI  - Quetiapine-Induced Hypomania and its Association with Quetiapine/Norquetiapine
      Plasma Concentrations: A Case Series of Bipolar Type 2 Patients.
AB  - International guidelines consider quetiapine at medium doses (300-400 mg/day) as
      valid options for the treatment of bipolar depression for the supposed lower risk
      of a switch to hypomania/mania than antidepressants. Norquetiapine is an active
      metabolite with antidepressant action. We describe three cases of induced
      hypomania in bipolar type 2 subjects who received quetiapine extended-release
      monotherapy (300 mg/day) for a mild/moderate major depressive episode. Quetiapine
      and norquetiapine plasma concentrations were measured after 1 week of treatment.
      Hypomania appeared after 7-10 days of quetiapine extended-release monotherapy and
      all subjects had a quetiapine/norquetiapine plasma concentration ratio <1. We
      propose a ratio value <1 as a predictor of risk for a switch to hypomania in
      bipolar depressed subjects receiving quetiapine extended-release monotherapy.
      Future research should ascertain the validity of this laboratory parameter to
      assess the risk of quetiapine-induced hypomania in large samples of bipolar
      patients.

PMID- 29063220
TI  - Assessment of a flexible robotic system for endoluminal applications and
      transanal total mesorectal excision (taTME): Could this be the solution we have
      been searching for?

PMID- 29063212
TI  - Staphylococcal Biofilms in Atopic Dermatitis.
AB  - PURPOSE OF REVIEW: Atopic dermatitis (AD) is a chronic, relapsing inflammatory
      skin disorder that is a major public health burden worldwide. AD lesions are
      often colonized by Staphylococcus aureus and Staphylococcus epidermidis. An
      important aspect of Staphylococcus spp. is their propensity to form biofilms,
      adhesive surface-attached colonies that become highly resistant to antibiotics
      and immune responses, and recent studies have found that clinical isolates
      colonizing AD skin are often biofilm-positive. Biofilm formation results in
      complex bacterial communities that have unique effects on keratinocytes and host
      immunity. This review will summarize recent studies exploring the role of
      staphyloccocal biofilms in atopic dermatitis and the implications for treatment.
      RECENT FINDINGS: Recent studies suggest an important role for biofilms in the
      pathogenesis of numerous dermatologic diseases including AD. S. aureus biofilms
      have been found to colonize the eccrine ducts of AD skin, and these biofilms
      influence secretion of keratinocyte cytokines and trigger differentiation and
      apoptosis of keratinocytes. These activities may act to disrupt barrier function
      and promote disease pathogenesis as well as allergen sensitization. Formation of
      biofilm is a successful strategy that protects the bacteria from environmental
      danger, antibiotics, and phagocytosis, enabling chronic persistence in the host.
      An increasing number of S. aureus skin isolates are resistant to conventional
      antibiotics, and staphylococcal biofilm communities are prevalent on the skin of
      individuals with AD. Staphylococcal colonization of the skin impacts skin barrier
      function and plays multiple important roles in AD pathogenesis.

PMID- 29063222
TI  - The Brain Drain Myth: Retention of Specialist Surgical Graduates in East, Central
      and Southern Africa 1974-2013.

PMID- 29063219
TI  - Treatment of obstructed defecation syndrome due to rectocele and rectal
      intussusception with a high volume stapler (TST STARR-plus).
AB  - BACKGROUND: In recent years, stapled transanal resection (STARR) has been adopted
      worldwide with convincing short-term results. However, due to the high recurrence
      rate and some major complications after STARR, there is still controversy about
      when the procedure is indicated. The aim of this study was to assess the safety,
      efficacy and feasibility of STARR performed with a new dedicated device for
      tailored transanal stapled surgery. METHODS: All the consecutive patients
      affected by obstructed defecation syndrome (ODS) due to rectocele or/and rectal
      intussusception, who underwent STARR with the TST STARR-Plus stapler, were
      included in a prospective study. Pain, Cleveland Clinic Score for Constipation
      (CCCS) and incontinence, patient satisfaction, number of hemostatic stitches,
      operative time, hospital stay and perioperative complications were recorded.
      Postoperative complications and recurrence were also reported. RESULTS: Forty
      five consecutive patients (median age 50; range 24-79) were included in the
      study. Median resected volume was 15 cm3 (range 12-19 cm3) with a median height
      of surgical specimen of 5.6 cm (range 4.5-10 cm). The mean CCCS decreased from
      17.26 (+/- 3.77) to 5.42 (+/- 2.78) postoperatively (p < 0.001). Patient
      satisfaction grade was excellent in 14 patients (31.1%), good in 25 (55.5%),
      sufficient in three (6.7%) and poor in three patients (6.7%). No major
      complications occurred. Five patients (11%) reported urgency after 30 days and
      two patients (4%) after 12 months. The Cleveland Clinic Incontinence score did
      not significantly change. At a median follow-up of 23 months (range 12-30
      months), only three patients (6.7%) reported recurrent symptoms of obstructed
      defecation comparable to those reported at baseline. CONCLUSIONS: TST STARR-Plus
      seems to be safe and effective for the treatment of ODS due to rectocele and
      rectal intussusception, and technical improvement could reduce the risk of some
      complications. However, careful patient selection is still the best means of
      preventing complications.

PMID- 29063221
TI  - High T2-weighted signal intensity for risk prediction of sudden cardiac death in
      hypertrophic cardiomyopathy.
AB  - In search of improved risk stratification in hypertrophic cardiomyopathy (HCM),
      CMR imaging has been implicated as a potential tool for prediction of sudden
      cardiac death (SCD). In follow-up of the promising results with extensive late
      gadolinium enhancement (LGE), high signal-intensity on T2-weighted imaging
      (HighT2) has become subject of interest given its association with markers of
      adverse disease progression, such as LGE, elevated troponin and non-sustained
      ventricular tachycardia. In lack of follow-up cohorts, we initiated an
      exploratory study on the association between HighT2 and the internationally
      defined risk categories of SCD. In a cohort of 109 HCM patients from a
      multicenter study on CMR imaging and biomarkers, we estimated the 5-year SCD risk
      (HCM Risk-SCD model). Patients were categorized as low (< 4%), intermediate (>= 4
      <6%) or high (>= 6%) risk. In addition, risk categorization according to the
      ACC/AHA guidelines was performed. HighT2 was present in 27% (29/109). Patients
      with HighT2 were more often at an intermediate-high risk of SCD according to the
      European (28 vs. 10%, p = .032) and American guidelines (41 vs. 18%, p = .010)
      compared to those without HighT2. The estimated 5-year SCD risk of our cohort was
      1.9% (IQR 1.3-2.9%), and projected SCD rates were higher in patients with than
      without HighT2 (2.8 vs. 1.8%, p = .002). In conclusion, HCM patients with HighT2
      were more likely to be intermediate-high risk, with projected SCD rates that were
      1.5 fold higher than in patients without HighT2. These pilot findings call for
      corroborative studies with more intermediate-high risk HCM patients and clinical
      follow-up to assess whether HighT2 may have additional value to current risk
      stratification.

PMID- 29063223
TI  - Preoperative Anemia and the Outcome After Coronary Artery Bypass Grafting: Reply.

PMID- 29063224
TI  - Predictors and Time-Based Hospital Mortality in Patients with Isolated and
      Polytrauma Brain Injuries.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major cause of morbidity and
      mortality worldwide. We studied the predictors and time-based mortality in
      patients with isolated and polytrauma brain injuries in a rapidly developing
      country. We hypothesized that TBI-related 30-day mortality is decreasing over
      time. METHODS: A retrospective analysis was conducted for all patients with
      moderate-to-severe TBI who were admitted directly to a level 1 trauma center
      between 2010 and 2014. Patient's data were analyzed and compared according to
      survival (survived vs. not survived), time (early death [2 days], intermediate [3
      7 days] versus late [>7 days]) post-injury, and type (polytrauma vs. isolated
      TBI). Cox proportional hazards models were performed for the predictors of
      mortality. RESULTS: A total of 810 patients were admitted with moderate-to-severe
      TBI with a median age of 27 years. Traffic-related injury was the main mechanism
      of TBI (65%). Isolated TBIs represented 22.6% of cases and 56% had head AIS >3.
      The overall mortality rate was 27%, and most of deaths occurred in the
      intermediate (40%) and early period (38%). The incidence of TBI was greater in
      patients aged 21-30 years but the mortality was proportionately higher among
      elderly. The average annual incidence was 8.43 per 100,000 population with an
      overall mortality of 2.28 per 100,000 population. Kaplan-Meier curves showed that
      polytrauma had greater mortality than isolated TBI. However, Cox survival
      analysis showed that age [Hazard ratio (HR) 1.02], scene GCS (HR
      0.86),subarachnoid hemorrhage (HR 1.7), and blood transfusion amount (HR 1.03)
      were the predictors of mortality regardless of being polytrauma or isolated TBI
      after controlling for 14 relevant covariates. CONCLUSIONS: The 30-day survival in
      patients with TBI is improving over the years in Qatar; however, the mortality
      remains high in the elderly males. The majority of deaths occurred within a week
      after the injury. Further studies are needed to assess the long-term survival in
      patients with moderate-to-severe TBI.

PMID- 29063225
TI  - Preperitoneal Surgical Approach to Treat Vesicoureteral Anastomotic Leakage,
      Distal Stenosis or Reflux After Kidney Transplantation.
AB  - BACKGROUND: If endourological approaches are not applicable to treat
      vesicoureteral anastomotic complications after kidney transplantation, the
      surgical gold standard in many transplant centers is pyeloureterostomy or
      ureteroureterostomy using the native ureter. We report an original preperitoneal
      technique that can be used for vesicoureteral reanastomosis in kidney transplant
      recipients not eligible for endourological treatment. METHODS: Between January
      2011 and December 2015, 18 kidney transplant recipients underwent this new
      surgical procedure. Of this number, 15 subjects with at least 1 year of follow-up
      were included in the analysis. The indications were vesicoureteral reflux,
      anastomotic stenosis, and leakage in 8, 5, and 2 patients, respectively. Briefly,
      a double J stent was preoperatively inserted into the grafted ureter. Surgery was
      performed through a Pfannenstiel incision. The preperitoneal space surrounding
      the bladder was dissected and the distal part of the grafted ureter was
      identified and mobilized. The anastomotic area was resected and another
      vesicoureteral anastomosis was performed (Lich-Gregoir technique), keeping the JJ
      stent in place for three weeks. RESULTS: This procedure was performed 213 days
      (range 17-2608) after kidney transplantation. Median surgical duration was 179
      minutes (range 112-314) and median hospital stay 8 days (range 4-14). The success
      rate was 86.7% (13/15), with a median follow-up of 1148 days (range 517-1808). In
      two patients, symptomatic recurrence of vesicoureteral reflux required a
      pyeloureterostomy using the native ureter. CONCLUSIONS: The authors describe a
      simple technique that avoids transperitoneal dissection, potentially yielding
      more esthetic results thanks to easy access, as well as excellent outcomes.

PMID- 29063226
TI  - Induced Granulation Tissue but not Artificial Dermis Enhances Early Host-Graft
      Interactions in Full-Thickness Burn Wounds.
AB  - BACKGROUND: Cellular grafts used for skin repair require rapid integration with
      the host tissue to remain viable and especially to nourish the epidermal cells.
      Here, we evaluated the responses in the split-thickness skin grafts (STSGs)
      grafted on three differently treated wound beds: directly on excised wound bed
      (EX), on an artificial dermal template (DT) and on granulation tissue (GT)
      induced by cellulose sponge. METHODS: In ten burn patients, after excision, a
      test area was divided into three sections: One transplanted with STSG
      instantaneously and two sections had a pre-treatment for 2 weeks with either DT
      or a cellulose sponge inducing granulation tissue formation and thereafter
      grafted with STSGs. RESULTS: One week after grafting, the STSGs on GT
      demonstrated most endothelial CD31+ staining, largest average vessel diameters as
      well as most CD163+ staining of M2-like macrophages and most MIB1+ proliferating
      epidermal cells, suggesting an active regenerative environment. STSGs on DT had
      smallest vessel diameters and the least CD163+ macrophages. STSGs on EX had the
      least CD31+ cells and the least MIB1+ proliferating cells. After 3 months, this
      reactivity in STSGs had subsided, except increased dermal cell proliferation was
      observed in STSGs on EX. CONCLUSIONS: Results show that pre-treatment of wound
      bed and induction of granulation tissue formation can accelerate host-graft
      interaction by stimulating graft vasculature and inducing cell proliferation.

PMID- 29063227
TI  - Implantation of Right Kidneys: Is the Risk of Technical Graft Loss Real?
AB  - BACKGROUND: The left kidney (LK) is preferred by transplant surgeons, because its
      vein is always of good length and has a thick wall that enables safe suturing. On
      the other hand, the right renal vein is generally shorter and thinner walled, and
      well known for its technical difficulty during venous anastomosis, and can result
      in graft loss. We examined our living (LD) and deceased donor (DD) recipient data
      and compared the incidence of technical graft loss and early graft function in
      right and left kidneys. METHODS: A cohort of 58 adult and pediatric recipients
      received an LD or DD kidney between January 2015 and December 2016. The donor and
      recipient data were retrieved and retrospectively analyzed. Technical graft loss
      was defined as graft thrombosis within the 7 days after transplant. RESULTS:
      Right kidneys (RKs) were not a risk factor for technical graft loss, and no graft
      was lost for technical reasons in either LD or DD transplants. Early graft
      function in LK and RKs was also comparable in the LD cohort, and there were no
      LKs in the DD cohort. CONCLUSION: Based on our data, the use of RKs was not a
      risk factor for technical graft loss and early graft function was comparable to
      LKs.

PMID- 29063228
TI  - Safety and Feasibility of a Ketamine Package to Support Emergency and Essential
      Surgery in Kenya when No Anesthetist is Available: An Analysis of 1216
      Consecutive Operative Procedures.
AB  - BACKGROUND: Lack of access to emergency and essential surgery is widespread in
      low- and middle-income countries. Scarce anesthesia services contribute to this
      unmet need. The aim of this study was to evaluate the safety and feasibility of
      the Every Second Matters for Emergency and Essential Surgery-Ketamine (ESM
      Ketamine) package for emergency and essential procedures when no anesthetist was
      available. METHODS: From November 2013 to September 2017, the ESM-Ketamine
      package was used for patients requiring emergency or life-improving surgeries in
      fifteen selected facilities across Kenya when no anesthetist was available. A
      mixed-methods approach was used to assess safety and feasibility of the ESM
      Ketamine package, including demand, acceptability, and practicality. The primary
      outcome was ketamine-related adverse events. Key-informant interviews captured
      perceptions of providers, hospital administrators, and surgeons/proceduralists.
      RESULTS: Non-anesthetist mid-level providers used ESM-Ketamine for 1216 surgical
      procedures across the fifteen study facilities. The median ketamine dose was 2.1
      mg/kg. Brief (<30 s) oxygen desaturations occurred in 39 patients (3%), and
      prolonged (>30 s) oxygen desaturations occurred in seven patients (0.6%). There
      were 157 (13%) reported cases of hallucinations and agitation which were treated
      with diazepam. All patients recovered uneventfully, and no ketamine-related
      deaths were reported. Twenty-seven key-informant interviews showed strong support
      for the program with four main themes: financial considerations, provision of
      services, staff impact, and scaling considerations. CONCLUSIONS: The ESM-Ketamine
      package appears safe and feasible and is capable of expanding access to emergency
      and essential surgeries in rural Kenya when no anesthetist is available.

PMID- 29063229
TI  - Interfacing with the nervous system: a review of current bioelectric
      technologies.
AB  - The aim of this study is to discuss the state of the art with regard to
      established or promising bioelectric therapies meant to alter or control
      neurologic function. We present recent reports on bioelectric technologies that
      interface with the nervous system at three potential sites-(1) the end organ, (2)
      the peripheral nervous system, and (3) the central nervous system-while exploring
      practical and clinical considerations. A literature search was executed on
      PubMed, IEEE, and Web of Science databases. A review of the current literature
      was conducted to examine functional and histomorphological effects of
      neuroprosthetic interfaces with a focus on end-organ, peripheral, and central
      nervous system interfaces. Innovations in bioelectric technologies are providing
      increasing selectivity in stimulating distinct nerve fiber populations in order
      to activate discrete muscles. Significant advances in electrode array design
      focus on increasing selectivity, stability, and functionality of implantable
      neuroprosthetics. The application of neuroprosthetics to paretic nerves or even
      directly stimulating or recording from the central nervous system holds great
      potential in advancing the field of nerve and tissue bioelectric engineering and
      contributing to clinical care. Although current physiotherapeutic and surgical
      treatments seek to restore function, structure, or comfort, they bear significant
      limitations in enabling cosmetic or functional recovery. Instead, the
      introduction of bioelectric technology may play a role in the restoration of
      function in patients with neurologic deficits.

PMID- 29063230
TI  - Models for estimation of the presence of non-regulated disinfection by-products
      in small drinking water systems.
AB  - Among all the organic disinfection by-products (DBPs), only trihalomethanes
      (THMs) and haloacetic acids (HAAs) are regulated in drinking water, while most
      DBPs are not. Very little information exists on the occurrence of non-regulated
      DBPs, particularly in small water systems (SWS). Paradoxically, SWS are more
      vulnerable to DBPs because of a low capacity to implement adequate treatment
      technologies to remove DBP precursors. Since DBP analyses are expensive, usually
      SWS have difficulties to implement a rigorous characterization of these
      contaminants. The purpose of this study was to estimate non-regulated DBP levels
      in SWS from easy measurements of relevant parameters regularly monitored. Since
      no information on non-regulated DBPs in SWS was available, a sampling program was
      carried out in 25 SWS in two provinces of Canada. Five DBP families were
      investigated: THMs, HAAs, haloacetonitriles (HANs), halonitromethanes (HNMs), and
      haloketones (HKs). Multivariate linear mixed regression models were developed to
      estimate HAN, HK, and HNM levels from water quality characteristics in the water
      treatment plant, concentrations of regulated DBPs, and residual disinfectant
      levels. The models obtained have a good explanatory capacity since R 2 varies
      from 0.77 to 0.91 according to compounds and conditions for application (season
      and type of treatment). Model validation with an independent database suggested
      their ability for generalization in similar SWS in North America.

PMID- 29063231
TI  - Modified single-stage segmental cricotracheal resection.
AB  - The objective of our work is to demonstrate in a large cohort of patients with
      cricotracheal stenosis that resection of long airway segments could be performed
      with no increased risk of postoperative complications. A consecutive series of
      patients getting cervical segmental cricotracheal resection (CTR) were reviewed.
      The typical segmental tracheal resection technique has been modified to
      accommodate long segment removal. Modifications include using trachea to enable
      the reconstruction of the larynx itself as well as the placement of a
      "laryngosternopexy" stitch between the thyroid lamina and the sternoclavicular
      ligament designed to take all of the tension off the anastomosis and to prevent
      inadvertent head extension. Anastomosis was performed by using continuous barbed
      sutures that allowed gradual approximation of the proximal and distal segments
      even in the presence of a large segmental airway resection defect that could
      involve as much as half of the tracheal length. Thirty-eight patients were
      treated. Primary etiologies of cricotracheal stenosis were prolonged intubation
      and tracheostomy. All had Grade III-IV stenosis. Only one patient had
      postoperative revision surgery for anastomosis-based disease. All patients with
      tracheostomy (n = 29) were successfully decannulated. Complications occurred in
      five patients. These included acute airway obstruction requiring emergency
      tracheostomy through the anastomosis, a tracheal dehiscence, laryngeal edema with
      airway obstruction, superficial wound infections, neck abscesses, and transient
      vocal cord immobility. Modified cricotracheal resection has comparable results to
      traditional techniques and may offer advantages such as resection of long
      tracheal segments without any increase in the risk of post-anastomosis airway
      leak.

PMID- 29063232
TI  - Psychological Predictors of Health Anxiety in Response to the Zika Virus.
AB  - The threat of a United States (U.S.) Zika virus pandemic during 2015-2016 was
      associated with public anxiety. Such threats represent opportunities to examine
      hypotheses about health anxiety. The present study investigated psychological
      predictors of Zika-related anxiety during the 2015-2016 outbreak. U.S. adults (N
      = 216) completed a battery of measures assessing Zika-related anxiety as well as
      psychological variables hypothesized to predict anxious responding to the threat
      of a domestic Zika outbreak. Contrary to hypotheses, regression analyses
      indicated that only contamination severity overestimates and greater Zika
      knowledge significantly predicted Zika-related anxiety. Study limitations and
      clinical implications are discussed.

PMID- 29063234
TI  - The growth of uterine myomas in untreated women: influence factors and ultrasound
      monitoring.
AB  - PURPOSE: Until now there are no systematic studies about the long-term course of
      myoma growth. Therefore, the aims of the present study were: (1) ultrasound
      monitoring of the natural course of growth of uterine leiomyomas; (2) assessment
      of whether the growth of myomas depends on the age of the patients, the location,
      or the initial size (possible co-factors/predictor criteria for increase of
      growth); influence of oral contraceptives (OC). METHODS: Patient records (2010
      May 2016) were retrospectively and systematically evaluated in regards to their
      growth and clinical course. The patients received a follow-up questionnaire by
      mail about the further history. Linear regression analysis and generalized
      regression analysis were performed to determine the influence of various factors
      on the growth of myomas. RESULTS: Overall, 152 met the further inclusion
      criteria. Most of the myomas increased in size but 10% of the myomas became
      smaller without therapy. There is a significant dependency between the initial
      myoma size, and the first and second measurements, but not between those measures
      and myoma localization. In regression analysis, there was also a significant
      association between the growth of the myomas and the initial size but no
      association with age, complaint symptoms, and use of OC. However, the use of OC
      waas significantly associated with myoma growth in GEE. CONCLUSIONS: The course
      of growth of myomas has large variance, so this should not be taken as a sign for
      a malignant event (sarcoma or the so-called STUMP). The growth takes place with
      considerable individual variability and ultimately is not predictable.

PMID- 29063236
TI  - Identification of differentially expressed genes regulated by molecular signature
      in breast cancer-associated fibroblasts by bioinformatics analysis.
AB  - OBJECTIVE: Breast cancer is a severe risk to public health and has adequately
      convoluted pathogenesis. Therefore, the description of key molecular markers and
      pathways is of much importance for clarifying the molecular mechanism of breast
      cancer-associated fibroblasts initiation and progression. Breast cancer
      associated fibroblasts gene expression dataset was downloaded from Gene
      Expression Omnibus database. METHODS: A total of nine samples, including three
      normal fibroblasts, three granulin-stimulated fibroblasts and three cancer
      associated fibroblasts samples, were used to identify differentially expressed
      genes (DEGs) between normal fibroblasts, granulin-stimulated fibroblasts and
      cancer-associated fibroblasts samples. The gene ontology (GO) and pathway
      enrichment analysis was performed, and protein-protein interaction (PPI) network
      of the DEGs was constructed by NetworkAnalyst software. RESULTS: Totally, 190
      DEGs were identified, including 66 up-regulated and 124 down-regulated genes. GO
      analysis results showed that up-regulated DEGs were significantly enriched in
      biological processes (BP), including cell-cell signalling and negative regulation
      of cell proliferation; molecular function (MF), including insulin-like growth
      factor II binding and insulin-like growth factor I binding; cellular component
      (CC), including insulin-like growth factor binding protein complex and integral
      component of plasma membrane; the down-regulated DEGs were significantly enriched
      in BP, including cell adhesion and extracellular matrix organization; MF,
      including N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase activity and
      calcium ion binding; CC, including extracellular space and extracellular matrix.
      WIKIPATHWAYS analysis showed the up-regulated DEGs were enriched in myometrial
      relaxation and contraction pathways. WIKIPATHWAYS, REACTOME, PID_NCI and KEGG
      pathway analysis showed the down-regulated DEGs were enriched endochondral
      ossification, TGF beta signalling pathway, integrin cell surface interactions,
      beta1 integrin cell surface interactions, malaria and glycosaminoglycan
      biosynthesis-chondroitin sulfate/dermatan sulphate. The top 5 up-regulated hub
      genes, CDKN2A, MME, PBX1, IGFBP3, and TFAP2C and top 5 down-regulated hub genes
      VCAM1, KRT18, TGM2, ACTA2, and STAMBP were identified from the PPI network, and
      subnetworks revealed these genes were involved in significant pathways, including
      myometrial relaxation and contraction pathways, integrin cell surface
      interactions, beta1 integrin cell surface interaction. Besides, the target hsa
      mirs for DEGs were identified. hsa-mir-759, hsa-mir-4446-5p, hsa-mir-219a-1-3p
      and hsa-mir-26a-5p were important miRNAs in this study. CONCLUSIONS: We pinpoint
      important key genes and pathways closely related with breast cancer-associated
      fibroblasts initiation and progression by a series of bioinformatics analysis on
      DEGs. These screened genes and pathways provided for a more detailed molecular
      mechanism underlying breast cancer-associated fibroblasts occurrence and
      progression, holding promise for acting as molecular markers and probable
      therapeutic targets.

PMID- 29063235
TI  - Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated
      with platinum-based chemotherapy.
AB  - PURPOSE: DNA mismatch repair (MMR) is a highly conserved biological pathway that
      plays a key role in maintaining genomic stability. MMR has been reported as a
      prognostic marker in certain cancers; however, the results are controversial.
      Therefore, identification of the prognostic value of MMR genes in ovarian cancer
      based on a large sample size is pivotal. METHODS: In the current study, we
      systemically investigated the prognostic roles of seven MMR genes, MSH2, MSH3,
      MSH6, MLH1, MLH3, PMS1 and PMS2, in ovarian cancer patients treated with platinum
      based chemotherapy through "The Kaplan-Meier plotter" (KM plotter) database,
      which contains gene expression data and survival information of ovarian cancer
      patients. RESULTS: Among seven MMR genes, high mRNA levels of MSH6, MLH1 and PMS2
      were significantly associated with a better overall survival for all ovarian
      cancer patients treated with platinum-based chemotherapy, especially in late
      stage and poor-differentiated ovarian cancer patients. Increased MSH6 and PMS2
      mRNA expression was correlated with a favorable overall survival in serous
      ovarian cancer patients. CONCLUSIONS: Our results indicate that sufficient MMR
      system is associated with an improved survival in ovarian cancer treated with
      platinum-based chemotherapy. MMR gene may be a potential prognosis predictor in
      ovarian cancer.

PMID- 29063237
TI  - A Tutorial Review on Multi-subject Decomposition of EEG.
AB  - Over the last years we saw a steady increase in the relevance of big neuroscience
      data sets, and with it grew the need for analysis tools capable of handling such
      large data sets while simultaneously extracting properties of brain activity that
      generalize across subjects. For functional magnetic resonance imaging, multi
      subject or group-level independent component analysis provided a data-driven
      approach to extract intrinsic functional networks, such as the default mode
      network. Meanwhile, this methodological framework has been adapted for the
      analysis of electroencephalography (EEG) data. Here, we provide an overview of
      the currently available approaches for multi-subject data decomposition as
      applied to EEG, and highlight the characteristics of EEG that warrant special
      consideration. We further illustrate the importance of matching one's choice of
      method to the data characteristics at hand by guiding the reader through a set of
      simulations. In sum, algorithms for group-level decomposition of EEG provide an
      innovative and powerful tool to study the richness of functional brain networks
      in multi-subject EEG data sets.

PMID- 29063239
TI  - Correction to: The sequence of disease-modifying therapies in relapsing multiple
      sclerosis: safety and immunologic considerations.
AB  - Unfortunately, the online published article has errors in Table 2. The
      Peginterferon is listed as IM, when it should be SC.

PMID- 29063233
TI  - Austrian consensus guidelines on the management and treatment of portal
      hypertension (Billroth III).
AB  - The Billroth III guidelines were developed during a consensus meeting of the
      Austrian Society of Gastroenterology and Hepatology (OGGH) and the Austrian
      Society of Interventional Radiology (OGIR) held on 18 February 2017 in Vienna.
      Based on international guidelines and considering recent landmark studies, the
      Billroth III recommendations aim to help physicians in guiding diagnostic and
      therapeutic strategies in patients with portal hypertension.

PMID- 29063238
TI  - Metabolic advantages and vulnerabilities in brain metastases.
AB  - Metabolic adaptations permit tumor cells to metastasize to and thrive in the
      brain. Brain metastases continue to present clinical challenges due to rising
      incidence and resistance to current treatments. Therefore, elucidating altered
      metabolic pathways in brain metastases may provide new therapeutic targets for
      the treatment of aggressive disease. Due to the high demand for glucose in the
      brain, increased glycolytic activity is favored for energy production. Primary
      tumors that undergo Warburg-like metabolic reprogramming become suited to growth
      in the brain microenvironment. Indeed, elevated metabolism is a predictor of
      metastasis in many cancer subtypes. Specifically, metabolic alterations are seen
      in primary tumors that are associated with the formation of brain metastases,
      namely breast cancer, lung cancer, and melanoma. Because of this selective
      pressure, inhibitors of key metabolic factors may reduce tumor cell viability,
      thus exploiting metabolic pathways for cancer therapeutics. This review
      summarizes the metabolic advantages and vulnerabilities of brain metastases.

PMID- 29063240
TI  - Corticobasal degeneration: key emerging issues.
AB  - Corticobasal degeneration (CBD) was first described by Rebeiz et al. in 1967, and
      was called corticodentatonigral degeneration with neuronal achromasia [1]. Since
      then, our knowledge of the clinical features and underlying tau pathology has
      grown tremendously. Clinical antemortem diagnosis of CBD pathology remains
      challenging and has led to the development of revised diagnostic criteria. As
      various clinical phenotypes may have CBD pathology, accurate prevalence studies
      are lacking. Recently, pooled prevalence of fronto-temporal lobar degeneration,
      PSP and CBS was reported as 10.6 per 100,000 [2]. Although rare, CBD is an
      important disease to understand because it provides a model of a specific
      proteinopathy (tauopathy) and, therefore, opportunity to study pathophysiology of
      tauopathies and efficacy of tau-directed therapies. In the past few years,
      identification of tau specific ligands has advanced neuroimaging of tauopathies
      such as CBD and progressive supranuclear palsy. However, clinical prediction of
      CBD pathology remains challenging and an active are of research. In this review,
      we highlight key emerging issues in CBD pathophysiology, genetics and novel
      neuroimaging techniques with tau ligands.

PMID- 29063241
TI  - Prevalence and clinical characteristics of cortical superficial siderosis in
      patients with acute stroke.
AB  - Cortical superficial siderosis (cSS) is a pathologic and radiologic diagnosis of
      hemosiderin deposition in subpial brain layers. However, cSS has not been fully
      studied in patients with acute stroke. Here, we investigated the prevalence of
      cSS in patients with acute stroke and analyzed the relationship between cSS and
      different clinical and neuroimaging characteristics. From September 2014 through
      June 2016, consecutive patients with acute stroke who were admitted to our
      department were retrospectively investigated. We analyzed the prevalence of cSS
      and the associations between cSS and risk factors, the topographic distribution
      of cerebral microbleeds (CMBs), and the severity of white matter lesions (WMLs).
      In total, 739 patients (589 patients with ischemic stroke/transient ischemic
      stroke [IS/TIA] and 150 with intracerebral hemorrhage [ICH]; mean age, 71.4
      years) were enrolled. We identified cSS in six (1.0%) patients with IS/TIA and
      seven (4.7%) patients with ICH. The presence of cSS was associated with ICH (P <
      0.0001), WMLs (P = 0.0105), and lobar and non-lobar CMBs (both P < 0.0001); no
      associations between cSS and age, sex, cardiovascular risk factors, IS subtype
      classification, or antiplatelet and anticoagulant therapy were found. In a
      multivariable logistic regression analysis, high numbers of lobar CMBs (>= 2;
      odds ratio, 11.03; 95% confidence interval, 2.03-205.40; P = 0.0029) were
      independently associated with cSS. Furthermore, cSS was often located near lobar
      CMBs. Our results suggest that cSS is prevalent in ICH and is independently
      associated with lobar CMBs; however, no associations between cSS and other risk
      factors or comorbidities were observed.

PMID- 29063243
TI  - Characterization of Charcot-Marie-Tooth optic neuropathy.
AB  - Varying degrees of optic neuropathy can be seen in patients with Charcot-Marie
      Tooth (CMT) disease. To define and characterize the extent of optic neuropathy in
      patients with CMT2A and CMT1A, two patients from both sub-classifications were
      evaluated. All patients underwent complete neuro-ophthalmic examinations, and
      optical coherence (OCT) measurements of the retinal nerve fiber layer (RNFL) and
      ganglion cell layer complex (GCC) were obtained, along with pattern visual evoked
      potential (VEP) and pattern electroretinogram (ERG) recordings. RNFL thickness
      measurements were decreased in both patients with CMT2A, and normal in both
      patients with CMT1A. GCC measurements were decreased in both patients with CMT2A,
      mildly decreased in one patient with CMT1A and normal in the second CMT1A
      patient. VEP latencies were delayed in one patient with CMT2A and one patient
      with CMT1A. VEP latencies were immeasurable in the other CMT2A patient and not
      obtained in the second CMT1A patient. Pattern ERG P50-N95 amplitudes were
      decreased in both patients with CMT2A and normal in one patient with CMT1A. The
      pattern ERG was immeasurable in the second patient with CMT1A. The pattern of
      RNFL and GCC thinning in CMT2A with optic neuropathy, a subset of HMSN VI,
      closely resembles that seen in other mitochondrial optic neuropathies.

PMID- 29063242
TI  - Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte
      glycoprotein antibody-associated syndromes: a multicenter study.
AB  - Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as
      a potential biomarker in patients with inflammatory demyelinating diseases of the
      central nervous system. We here compare the clinical and laboratory findings
      observed in a cohort of MOG-Ab seropositive and seronegative cases and describe
      IgG subclass analysis results. Consecutive serum samples referred to Verona
      University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab
      testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab
      was determined using a cell-based assay. A live cell immunofluorescence assay was
      used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed
      samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration
      of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of
      425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive
      patients were mainly characterised by the involvement of the optic nerve and/or
      spinal cord. Half of the cases presented relapses and the recovery was usually
      partial. Brain MRI was heterogeneous while short lesions were the prevalent
      observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing
      cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were
      predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies
      were also detectable. We confirm that MOG-Ab-related syndromes have distinct
      features in the spectrum of demyelinating conditions, and we describe the
      possible role of the different IgG subclasses in this condition.

PMID- 29063246
TI  - Correction to: The Aging Urban Brain: Analyzing Outdoor Physical Activity Using
      the Emotiv Affectiv Suite in Older People.
AB  - Please note that the legend to Fig. 1 has been modified since this article was
      originally published, and also that in Tables 2, 3 and 4, R[2] was corrected to
      (the now correct) R squared.

PMID- 29063245
TI  - Transparenchymal glissonean approach: a novel surgical technique for advanced
      perihilar bile duct cancer.
AB  - PURPOSE: To increase the surgical opportunities for locally advanced perihilar
      bile duct cancers that require left-sided hepatectomies, we developed the
      transparenchymal glissonean approach (TGA); it comprises intra-hepatic exposure
      and dissection of the Glisson's sheath to gain access to the hepatic artery and
      portal vein for reconstruction. METHODS: Following skeletonization of the
      hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If
      extra-hepatic attempts to access the distal portions of the invaded vessels fail,
      TGA can be used. The distal portion of the invaded right or right posterior
      Glisson's sheath is exposed following liver transection. The anterior portion of
      the wall of bile duct is cut and transected circumferentially including the
      fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated
      and dissected towards the hepatic hilum until the invaded distal portion of the
      vessels, and vascular reconstructions are performed. RESULTS: TGA was performed
      in 9 patients; 5 patients underwent left hemihepatectomy and 4 underwent left tri
      sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo
      classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients,
      respectively. No patients had CDC grades IV and V disease. Pathologically, all
      cases were pT4; 3 cases were R0, 5 were R1 with microscopic positive margin, and
      2 were R1 with microscopic metastasis. The overall median survival time was 25.0
      months. CONCLUSIONS: TGA is feasible with acceptable prognosis and expands the
      surgical opportunities.

PMID- 29063244
TI  - Efficacy of fingolimod and interferon beta-1b on cognitive, MRI, and clinical
      outcomes in relapsing-remitting multiple sclerosis: an 18-month, open-label,
      rater-blinded, randomised, multicentre study (the GOLDEN study).
AB  - Cognitive impairment (CI) affects 40-65% of multiple sclerosis (MS) patients.
      This study attempted evaluating the effects of fingolimod and interferon beta-1b
      (IFN beta-1b) on CI progression, magnetic resonance imaging (MRI) and clinical
      outcomes in relapsing-remitting MS (RRMS) patients over 18 months. The GOLDEN
      study was a pilot study including RRMS patients with CI randomised (2:1) to
      fingolimod (0.5 mg daily)/IFN beta-1b (250 ug every other day). CI was assessed
      via Rao's Brief Repeatable Battery and Delis-Kaplan Executive Function System
      test. MRI parameters, Expanded Disability Status Scale scores and relapses were
      measured. Overall, 157 patients were randomised, of whom 30 discontinued the
      study (fingolimod, 8.49%; IFN beta-1b, 41.18%; p <= 0.0001). Patients randomised
      to fingolimod had more severe clinical and MRI disease characteristics at
      baseline compared with IFN beta-1b. At Month (M) 18, both treatment groups showed
      improvements in all cognitive parameters. At M18, relapse rate, total number and
      volume of T2/T1 gadolinium-enhancing lesions were higher with IFN beta-1b, as
      well as the percentage brain volume change during the study. Safety and
      tolerability of both treatments were similar to previous studies. Both treatments
      showed improvements in cognitive parameters. Fingolimod demonstrated
      significantly better effects on MRI parameters and relapse rate. Imbalance in
      baseline characteristics and the drop-out pattern may have favoured IFN beta-1b.
      A longer duration trial may be needed to observe the complete expression of
      differential effects on CI scales reflecting the between-groups differences on
      MRI. Although limited in size, the GOLDEN study confirms the favourable benefit
      risk profile of fingolimod reported in previous studies.

PMID- 29063247
TI  - Methodological considerations of terrestrial laser scanning for vegetation
      monitoring in the sagebrush steppe.
AB  - Terrestrial laser scanning (TLS) provides fast collection of high-definition
      structural information, making it a valuable field instrument to many monitoring
      applications. A weakness of TLS collections, especially in vegetation, is the
      occurrence of unsampled regions in point clouds where the sensor's line-of-sight
      is blocked by intervening material. This problem, referred to as occlusion, may
      be mitigated by scanning target areas from several positions, increasing the
      chance that any given area will fall within the scanner's line-of-sight from at
      least one position. Because TLS collections are often employed in remote regions
      where the scope of sampling is limited by logistical factors such as time and
      battery power, it is important to design field protocols which maximize
      efficiency and support increased quantity and quality of the data collected. This
      study informs researchers and practitioners seeking to optimize TLS sampling
      methods for vegetation monitoring in dryland ecosystems through three analyses.
      First, we quantify the 2D extent of occluded regions based on the range from
      single scan positions. Second, we measure the efficacy of additional scan
      positions on the reduction of 2D occluded regions (area) using progressive
      configurations of scan positions in 1 ha plots. Third, we test the
      reproducibility of 3D sampling yielded by a 5-scan/ha sampling methodology using
      redundant sets of scans. Analyses were performed using measurements at analysis
      scales of 5 to 50 cm across the 1-ha plots, and we considered plots in grass and
      shrub-dominated communities separately. In grass-dominated plots, a center-scan
      configuration and 5 cm pixel size sampled at least 90% of the area up to 18 m
      away from the scanner. In shrub-dominated plots, sampling at least 90% of the
      area was only achieved within a distance of 12 m. We found that 3 and 5 scans/ha
      are needed to sample at least ~ 70% of the total area (1 ha) in the grass and
      shrub-dominated plots, respectively, using 5 cm pixels to measure sampling
      presence-absence. The reproducibility of 3D sampling provided by a 5 position
      scan layout across 1-ha plots was 50% (shrub) and 70% (grass) using a 5-cm voxel
      size, whereas at the 50-cm voxel scale, reproducibility of sampling was nearly
      100% for all plot types. Future studies applying TLS in similar dryland
      environments for vegetation monitoring may use our results as a guide to
      efficiently achieve sampling coverage and reproducibility in datasets.

PMID- 29063248
TI  - Discrepancies between coronary CT angiography and invasive coronary angiography
      with focus on culprit lesions which cause future cardiac events.
AB  - OBJECTIVES: To evaluate the clinical significance of discrepant lesions between
      coronary computed tomography angiography (CCTA) and invasive coronary angiography
      (ICA) in a longitudinal study. METHODS: In 220 patients with suspected coronary
      artery disease (CAD) who underwent both 256-row CCTA and ICA, the obstructive CAD
      (>= 50% stenosis) on CCTA was compared with that on ICA as the reference
      standard. We analysed the causes of the discrepancy between CCTA and ICA. During
      a 40-month follow-up period, major adverse cardiac events (MACE) were assessed.
      RESULTS: Discordance between CCTA and ICA was observed in 121 of the 3166
      coronary artery segments (3.8%). Common causes were calcification (45.9%) and
      positive remodelling (PR) (29.6%) in 83 false positive lesions, and noise (40.0%)
      and motion artefact (37.8%) in 38 false negative lesions. MACE occurred in seven
      lesions among the discrepant lesions; six among the 29 PR lesions (20.7%) and one
      among the 53 calcified lesions (1.9%). With respect to the prediction power of
      MACE in an intermediate stenosis, the CCTA-related value including PR was higher
      than the ICA-related value. CONCLUSIONS: PR was a frequent cause of MACE among
      the false positive lesions on CCTA. Therefore, the presence of PR on CCTA may
      suggest clinical significance, although it can be missed by ICA. KEY POINTS: *
      Compared to ICA, PR in CCTA may be cause of false positive lesion. * CCTA-related
      value including PR shows higher prediction power of MACE than ICA-related value.
      * PR reflects atherosclerotic burden that can be related to cardiac events. * PR
      in CCTA should be observed carefully, even if it is false positive.

PMID- 29063249
TI  - Early US findings of biliary atresia in infants younger than 30 days.
AB  - PURPOSE: To investigate and compare ultrasound (US) findings for the diagnosis of
      biliary atresia (BA) in infants younger than 30 days with those of infants older
      than 30 days. MATERIALS AND METHODS: From 2000 to 2015, we reviewed hepatobiliary
      US images in 12 BA infants younger than 30 days (younger BA group) and 62 BA
      infants older than 30 days (older BA group) before Kasai procedure. Eight (67%)
      of younger BA group underwent follow-up US examinations before Kasai procedure.
      Our review of the images focused on triangular cord sign, gallbladder (GB)
      abnormalities, vascular changes, and signs of portal hypertension. RESULTS: The
      triangular cord sign was present in 17% of younger BA group and in 56% of older
      BA group (P=.024). GB abnormalities were commonly identified in both groups. The
      hepatic artery diameter was significantly smaller in younger BA group than in
      older BA group (P<.001). Signs of portal hypertension were less common in younger
      BA group (17%) than in older BA group (84%) (P<.001). Follow-up US of two infants
      in younger BA group showed a new appearance of the triangular cord sign.
      CONCLUSION: BA infants younger than 30 days showed atypical US findings compared
      with those older than 30 days. KEY POINTS: * BA infants younger than 30 days show
      atypical US findings. * GB abnormalities were common in both younger and older BA
      group. * Subsequent US examination may be helpful to diagnose BA in young
      infants.

PMID- 29063250
TI  - Whole-tumour diffusion kurtosis MR imaging histogram analysis of rectal
      adenocarcinoma: Correlation with clinical pathologic prognostic factors.
AB  - OBJECTIVE: To investigate potential relationships between diffusion kurtosis
      imaging (DKI)-derived parameters using whole-tumour volume histogram analysis and
      clinicopathological prognostic factors in patients with rectal adenocarcinoma.
      MATERIAL AND METHODS: 79 consecutive patients who underwent MRI examination with
      rectal adenocarcinoma were retrospectively evaluated. Parameters D, K and
      conventional ADC were measured using whole-tumour volume histogram analysis.
      Student's t-test or Mann-Whitney U-test, receiver operating characteristic curves
      and Spearman's correlation were used for statistical analysis. RESULTS: Almost
      all the percentile metrics of K were correlated positively with nodal
      involvement, higher histological grades, the presence of lymphangiovascular
      invasion (LVI) and circumferential margin (CRM) (p<0.05), with the exception of
      between K10th, K90th and histological grades. In contrast, significant negative
      correlations were observed between 25th, 50th percentiles and mean values of ADC
      and D, as well as ADC10th, with tumour T stages (p< 0.05). Meanwhile, lower 75th
      and 90th percentiles of ADC and D values were also correlated inversely with
      nodal involvement (p< 0.05). Kmean showed a relatively higher area under the
      curve (AUC) and higher specificity than other percentiles for differentiation of
      lesions with nodal involvement. CONCLUSION: DKI metrics with whole-tumour volume
      histogram analysis, especially K parameters, were associated with important
      prognostic factors of rectal cancer. KEY POINTS: * K correlated positively with
      some important prognostic factors of rectal cancer. * K mean showed higher AUC
      and specificity for differentiation of nodal involvement. * DKI metrics with
      whole-tumour volume histogram analysis depicted tumour heterogeneity.

PMID- 29063251
TI  - Management of subcentimetre arterially enhancing and hepatobiliary hypointense
      lesions on gadoxetic acid-enhanced MRI in patients at risk for HCC.
AB  - OBJECTIVES: To investigate the significance of subcentimetre (<=1 cm) arterially
      enhancing and hepatobiliary hypointense lesions (SAELs) observed on gadoxetic
      acid-enhanced magnetic resonance imaging (MRI) of patients at risk of
      hepatocellular carcinoma (HCC). METHODS: A SAEL was defined as a subcentimetre
      hypervascular nodule exhibiting a hepatobiliary phase defect on gadoxetic acid
      enhanced MRI. We included 52 SAELs from 46 patients in a HCC surveillance
      population. The HCC reference standard was pathologic confirmation or a nodule >1
      cm with typical imaging features of HCC at follow-up imaging. The malignancy rate
      and HCC-favourable imaging findings of SAELs were evaluated. RESULTS: The
      malignancy rate among SAELs was 57.7% (30/52). At diagnosis, all SAELs that
      progressed to overt HCC were treatable with curative intention. Venous or late
      dynamic phase washout was more frequently observed with malignant SAELs than with
      benign SAELs (57.7% vs. 30.6%; P = 0.01). If SAELs exhibiting washout were
      considered as HCC, sensitivity, specificity, and positive predictive value was
      83.3%, 50%, and 69.4%, respectively. CONCLUSION: Among patients at risk of HCC,
      SAELs on gadoxetic acid-enhanced MRI exhibited high malignant potential. However,
      close observation may be an appropriate strategy for isolated SAELs. A washout
      appearance may be helpful for predicting malignancy. KEY POINTS: * Gadoxetic acid
      enhanced MRI provides hepatobiliary phase (HBP) images. * Screening frequently
      detects subcentimetre arterially enhancing and hepatobiliary hypointense lesions
      (SAELs). * A majority of SAELs progressed to overt HCC within 2 years. * A venous
      phase washout appearance correlated significantly with malignancy in SAELs.

PMID- 29063253
TI  - Risk factors for haemoptysis after percutaneous transthoracic needle biopsies in
      4,172 cases: Focusing on the effects of enlarged main pulmonary artery diameter.
AB  - OBJECTIVES: To evaluate the risk factors for haemoptysis after cone-beam computed
      tomography (CBCT)-guided percutaneous transthoracic needle biopsy (PTNB),
      particularly on whether the enlargement of main pulmonary artery diameter (mPAD)
      is a risk factor for PTNB-related haemoptysis. METHODS: 4,172 cases of CBCT
      guided PTNBs in 3,840 patients were retrospectively included in this study.
      Various data including mPAD measured on preprocedural CT images were evaluated
      using logistic regression analyses to determine significant risk factors for both
      haemoptysis and severe haemoptysis, designated as when blood transfusion,
      vascular embolisation or cardiopulmonary resuscitation were required to manage
      patients with haemoptysis. RESULTS: Haemoptysis occurred in 5.78 % (241/4172) of
      all PTNB procedures, while severe haemoptysis occurred in 0.18 % (7/4172). Female
      sex, history of antiplatelet or anticoagulative drugs, prolonged activated
      partial thromboplastin time, subsolid nodules, cavitary nodules and long pleura
      to-target distance were revealed to be independent risk factors for haemoptysis,
      while mPAD enlargement (> 29.5 mm) was not. Regarding severe haemoptysis,
      however, mPAD enlargement was demonstrated to be an independent risk factor along
      with the presence of subsolid and cavitary target nodules. CONCLUSION: mPAD
      enlargement was not a significant risk factor for PTNB-related haemoptysis;
      however, it was a significant risk factor for severe haemoptysis. KEY POINTS: *
      mPAD enlargement was a significant risk factor for severe PTNB-related
      haemoptysis. * mPAD can be useful in screening high-risk patients for severe
      haemoptysis. * Subsolid or cavitary nodule was another significant risk factor
      for severe haemoptysis.

PMID- 29063252
TI  - Radiologist involvement is associated with reduced use of MRI in the acute period
      of low back pain in a non-elderly population.
AB  - PURPOSE: To test the hypothesis that "acute-period" lumbar MRI in non-elderly
      patients with low back pain is less frequently performed at clinics/hospitals
      with greater involvement of full-time radiologists in the imaging workflow.
      METHODS: In a national-level claims database, we identified 14,819 non-elderly
      patients (mean age: 38.7+/-8.0 years) who visited clinics/hospitals for low back
      pain in 2013-2015. We classified the clinics/hospitals into four groups based on
      the level of full-time radiologist involvement and MRI ownership, and compared
      the frequency of acute-period lumbar MRI using hierarchical logistic regression
      analysis. RESULTS: Patients visiting facilities without a full-time radiologist
      (n=2105) were significantly (p<0.001) more likely to undergo acute-period MRI
      than those visiting facilities with >=1 radiologist partially managing imaging
      workflow (level-1, n=491) or >=1 radiologist intensively involved in imaging
      workflow (level-2, n=1190) (15.7% vs. 6.9% and 7.3%; adjusted odds ratio of no
      radiologist versus level-2: 2.93, p=0.018). No difference was observed between
      level-1 and level-2 involvement. CONCLUSIONS: Facilities with no full-time
      radiologist were more likely to perform acute-period MRI to assess for low back
      pain, while no difference was seen between facilities with varying levels of
      radiologist involvement in the imaging workflow. Radiologist involvement may
      contribute to optimal utilisation of medical imaging. KEY POINTS: * Lumbar MRI
      was more frequently performed at facilities without full-time radiologists. *
      Full-time radiologists may play an important role in appropriate utilisation of
      imaging. * Frequency of MRI was similar between moderate and intensive
      radiologist involvement.

PMID- 29063255
TI  - Gadolinium retention after administration of contrast agents based on linear
      chelators and the recommendations of the European Medicines Agency.
AB  - : The Pharmacovigilance Risk Assessment Committee (PRAC) of the European
      Medicines Agency (EMA) earlier this year recommended to suspend some marketing
      authorisations for Gadolinium Containing Contrast Agents (GCCAs) based on linear
      chelators due to the potential risk of gadolinium retention in the human body.
      These recommendations have recently been re-evaluated by EMA's Committee for
      Medicinal Products for Human Use (CHMP), and confirmed the final opinion of the
      European Medicines Agency. This editorial provides an overview of the available
      GCCAs and summarises the recent evidence of gadolinium retention. Moreover, a
      critical appraisal of the strengths and limitations of the scientific evidence
      currently available on gadolinium retention is given. KEY POINTS: * EMA
      recommended suspension of some EU marketing authorisations of four linear GCCAs.
      * Brain MRI findings indicating gadolinium retention have been confirmed by mass
      spectrometry. * Current scientific evidence for gadolinium retention has several
      methodological limitations. * No clear clinical evidence exists indicating that
      gadolinium retention causes neurotoxicity. * Long-term safety of GCCAs, however,
      remains unclear.

PMID- 29063254
TI  - Dual-layer DECT for multiphasic hepatic CT with 50 percent iodine load: a matched
      pair comparison with a 120 kVp protocol.
AB  - OBJECTIVES: To evaluate the image quality and lesion conspicuity of virtual
      monochromatic-imaging (VMI) with dual-layer DECT (DL-DECT) for reduced-iodine
      load multiphasic-hepatic CT. METHODS: Forty-five adults with renal dysfunction
      who had undergone hepatic DL-DECT with 300-mgI/kg were included. VMI (40-70-keV,
      DL-DECT-VMI) was generated at each enhancement phase. As controls, 45 matched
      patients undergoing standard 120-kVp protocol (120-kVp, 600-mgI/kg, and iterative
      reconstruction) were included. We compared the size-specific dose estimate
      (SSDE), image noise, CT attenuation, and contrast-to-noise ratio (CNR) between
      protocols. Two radiologists scored the image quality and lesion conspicuity.
      RESULTS: SSDE was significantly lower in DL-DECT group (p < 0.01). Image noise of
      DL-DECT-VMI was almost constant at each keV (differences of <=15%) and equivalent
      to or lower than of 120-kVp. As the energy decreased, CT attenuation and CNR
      gradually increased; the values of 55-60 keV images were almost equivalent to
      those of standard 120-kVp. The highest scores for overall quality and lesion
      conspicuity were assigned at 40-keV followed by 45 to 55-keV, all of which were
      similar to or better than of 120-kVp. CONCLUSIONS: For multiphasic-hepatic CT
      with 50% iodine-load, DL-DECT-VMI at 40- to 55-keV provides equivalent or better
      image quality and lesion conspicuity without increasing radiation dose compared
      with standard 120-kVp protocol. KEY POINTS: * 40-55-keV yields optimal image
      quality for half-iodine-load multiphasic-hepatic CT with DL-DECT. * DL-DECT
      protocol decreases radiation exposure compared with 120-kVp scans with iterative
      reconstruction. * 40-keV images maximise conspicuity of hepatocellular carcinoma
      especially at hepatic-arterial phase.

PMID- 29063256
TI  - Sciatic neurosteatosis: Relationship with age, gender, obesity and height.
AB  - AIM: To evaluate inter-reader performance for cross-sectional area and fat
      quantification of bilateral sciatic nerves on MRI and assess correlations with
      anthropometrics. METHODS: In this IRB-approved, HIPPA-compliant study, three
      readers performed a cross-sectional analysis of 3T lumbosacral plexus MRIs over
      an 18-month period. Image slices were evaluated at two levels (A and B). The
      sciatic nerve was outlined using a free hand region of interest tool on PACS.
      Proton-density fat fraction (FF) and cross-sectional areas were recorded. Inter
      reader agreement was assessed using intra-class correlation coefficient (ICC).
      Spearman correlation coefficients were used for correlations with age, BMI and
      height and Wilcoxon rank sum test was used to assess gender differences. RESULTS:
      A total of 67 patients were included in this study with male to female ratio of
      1:1. Inter-reader agreement was good to excellent for FF measurements at both
      levels (ICC=0.71-0.90) and poor for sciatic nerve areas (ICC=0.08-0.27). Positive
      correlations of sciatic FF and area were seen with age (p value<0.05). Males had
      significantly higher sciatic intraneural fat than females (p<0.05). CONCLUSION:
      Fat quantification MRI is highly reproducible with significant positive
      correlations of sciatic FF and area with age, which may have implications for MRI
      diagnosis of sciatic neuropathy. KEY POINTS: * MR proton density fat fraction is
      highly reproducible at multiple levels. * Sciatic intraneural fat is positively
      correlated with increasing age (p < 0.05). * Positive correlations exist between
      bilateral sciatic nerve areas and age (p < 0.05). * Males had significantly
      higher sciatic intraneural fat than females (p < 0.05).

PMID- 29063257
TI  - Detection of lung carcinoma with predominant ground-glass opacity on CT using
      temporal subtraction method.
AB  - PURPOSE: To evaluate the usefulness of the CT temporal subtraction (TS) method
      for the detection of the lung cancer with predominant ground-glass opacity (LC
      pGGO). MATERIALS AND METHODS: Twenty-five pairs of CT and their TS images in
      patients with LC-pGGO (31 lesions) and 25 pairs of those in patients without
      nodules were used for an observer performance study. Eight radiologists
      participated and the statistical significance of differences with and without the
      CT-TS was assessed by JAFROC analysis. RESULTS: The average figure-of-merit (FOM)
      values for all radiologists increased to a statistically significant degree, from
      0.861 without CT-TS to 0.912 with CT-TS (p < .001). The average sensitivity for
      detecting the actionable lesions improved from 73.4 % to 85.9 % using CT-TS. The
      reading time with CT-TS was not significantly different from that without.
      CONCLUSION: The use of CT-TS improves the observer performance for the detection
      of LC-pGGO. KEY POINTS: * CT temporal subtraction can improve the detection
      accuracy of lung cancer. * Reading time with temporal subtraction is not
      different from that without. * CT temporal subtraction improves observer
      performance for ground-glass/subsolid nodule detection.

PMID- 29063258
TI  - NMR relaxation parameters of methyl groups as a tool to map the interfaces of
      helix-helix interactions in membrane proteins.
AB  - In the case of soluble proteins, chemical shift mapping is used to identify the
      intermolecular interfaces when the NOE-based calculations of spatial structure of
      the molecular assembly are impossible or impracticable. However, the reliability
      of the membrane protein interface mapping based on chemical shifts or other
      relevant parameters was never assessed. In the present work, we investigate the
      predictive power of various NMR parameters that can be used for mapping of helix
      helix interfaces in dimeric TM domains. These parameters are studied on a dataset
      containing three structures of helical dimers obtained for two different proteins
      in various membrane mimetics. We conclude that the amide chemical shifts have
      very little predictive value, while the methyl chemical shifts could be used to
      predict interfaces, though with great care. We suggest an approach based on
      conversion of the carbon NMR relaxation parameters of methyl groups into
      parameters of motion, and one of such values, the characteristic time of methyl
      rotation, appears to be a reliable sensor of interhelix contacts in transmembrane
      domains. The carbon NMR relaxation parameters of methyl groups can be measured
      accurately and with high sensitivity and resolution, making the proposed
      parameter a useful tool for investigation of protein-protein interfaces even in
      large membrane proteins. An approach to build the models of transmembrane dimers
      based on perturbations of methyl parameters and TMDOCK software is suggested.

PMID- 29063259
TI  - [What is new in symptomatic MS treatment: Part 2-gait disorder and spasticity].
AB  - The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar
      importance as immunotherapy within a comprehensive concept of therapy of this
      chronic disease, since it contributes considerably to the reduction of
      disabilities in activities of daily living as well as social and occupational
      life. Moreover, symptomatic treatment is of great importance for amelioration of
      quality of life. Since our last survey of symptomatic MS treatment in 2004 and
      publication of the guidelines of the German Neurological Society and the
      Klinisches Kompetenznetz Multiple Sklerose (KKN-MS) in 2014 several developments
      within the topics of mobility, bladder and sexual function, vision, fatigue,
      cognition and rehabilitation took place. These new findings together with further
      aspects of disease measures and overall treatment strategies of the respective
      symptoms, as well as treatment goals are introduced in a series of six individual
      contributions. Here, the symptoms of gait disorders and spasticity will be
      discussed.

PMID- 29063260
TI  - [Childhood stroke : What are the special features of childhood stroke?]
AB  - Childhood arterial ischemic stroke differs in essential aspects from adult
      stroke. It is rare, often relatively unknown among laypersons and physicians and
      the wide variety of age-specific differential diagnoses (stroke mimics) as well
      as less established care structures often lead to a considerable delay in the
      diagnosis of stroke. The possible treatment options in childhood are mostly off
      label. Experiences in well-established acute treatment modalities in adult
      stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in
      children and only based on case reports and case series. The etiological
      clarification is time-consuming due to the multitude of risk factors which must
      be considered. Identifying each child's individual risk profile is mandatory for
      acute treatment and secondary prevention strategies and has an influence on the
      individual outcome. In addition to the clinical neurological outcome the residual
      neurological effects of stroke on cognition and behavior are decisive for the
      integration of the child into its educational, later professional and social
      environment.

PMID- 29063261
TI  - [What is new in symptomatic MS treatment: Part 1-introduction and methodical
      approach, ataxia and tremor].
AB  - The symptomatic treatment of multiple sclerosis (MS) nowadays is of similar
      importance as immunotherapy within a comprehensive concept of therapy of this
      chronic disease, since it contributes considerably to the reduction of
      disabilities in activities of daily living as well as social and occupational
      life. Moreover, symptomatic treatment is of great importance for amelioration of
      quality of life. Since our last survey of symptomatic MS treatment in 2004 and
      publication of the guidelines of the German Neurological Society and the
      Klinisches Kompetenznetz Multiple Sklerose (KKN-MS) in 2014 several developments
      within the topics of mobility, bladder and sexual function, vision, fatigue,
      cognition and rehabilitation took place. These new findings together with further
      aspects of disease measures and overall treatment strategies of the respective
      symptoms, as well as treatment goals are introduced in a series of six individual
      contributions. Here, the topic will be introduced, the methodical approach will
      be explained, and the treatment of ataxia and tremor will be discussed.

PMID- 29063262
TI  - [Neurointensive care in Germany : Results of an inspection of intensive care
      units].
AB  - BACKGROUND: The situation of neurointensive care in Germany is unclear.
      OBJECTIVES: An inspection of neurointensive wards should help to clarify the
      situation. MATERIALS AND METHODS: On the occasion of stroke unit certification
      audits, 320 intensive care units (39 independent neurological and 20
      neurosurgical, 6 combined neurological/neurosurgical, 253 interdisciplinary
      intensive wards) were inspected. RESULTS: On the 39 neurological and the 20
      neurosurgical intensive care units, a physician with intensive care
      specialization was available in 92% and 100% of units, respectively, and a
      physician with authorization for intensive care training was available in 74% and
      80% of units, respectively. A whole day shiftwork existed in 59% and 55% of
      units, respectively. On the interdisciplinary wards a physician with intensive
      care specialization was available in 76% and a physician with authorization for
      intensive care training was available in 52% of units. A whole day shiftwork
      existed in 64% of units. A full-time neurological/neurosurgical presence during
      business hours was found only in 18% of units. CONCLUSIONS: The
      neurological/neurosurgical presence and the opportunities for intensive care
      training on the interdisciplinary wards are not sufficient. There is an urgent
      need for improvement.

PMID- 29063263
TI  - [Healthcare research in forensic commitment or poking around in the dark :
      Consensus paper on the necessity for more uniform and better data].
AB  - Complex trends in occupancy determined by many influencing factors, clear state
      specific differences in imprisonment practices as well as recently implemented
      statutory alterations to the appropriate paragraphs in criminal law, underline
      the necessity for qualitative high-grade concomitant research of German forensic
      commitment; however, neither the structural prerequisites nor an adequate data
      situation are currently present in order to do justification to this aim. Not
      even the total number of patients currently accommodated in forensic commitment
      can be elucidated from the publicized (partial) statistics. This consensus paper,
      which was formulated by three research institutes active at the state level,
      describes the limited possibilities for current forensic healthcare research and
      raises the demand for a nationwide uniform data situation on patients in forensic
      commitment. Furthermore, how the appropriate elicitation instrument should be
      organizationally and structurally achieved, is sketched from a scientific
      perspective. This article aims at initiating a discussion on a sustainable
      improvement in the prerequisites for healthcare research in German forensic
      commitment and targets a sensitization of decision makers in politics and
      administration for this topic.

PMID- 29063264
TI  - Neurosurgical pathology of limited dorsal myeloschisis.
AB  - PURPOSE: The term limited dorsal myeloschisis (LDM) was used by Pang et al.
      (2010) to describe a distinct clinicopathological entity. LDMs are characterized
      by two invariable features: a focal-closed neural tube defect and a fibroneural
      stalk that links the skin lesion to the underlying spinal cord. METHODS: We
      retrospectively analyzed the neurosurgical pathologic findings of four LDM
      patients. RESULTS: Case 1 had a saccular skin lesion with nonterminal abortive
      myelocystocele at T11-12. Cases 2, 3, and 4 had a non-saccular (flat) skin lesion
      in the lumbosacral region. The morphologic features of the lesion in case 2 were
      those of meningocele manque. Cases 3 and 4 had accompanying non-LDM anomalies,
      caudal-type lipoma and type II split-cord malformation with neurenteric cyst,
      respectively. At preoperative diagnosis of the LDM stalk, magnetic resonance
      imaging, including 3D heavily T2-weighted image was useful; however, minute
      findings were often missed in the complicated cases 3 and 4. All patients had a
      favorable outcome following untethering of the stalk from the cord. The central
      histopathological feature of the LDM stalk is neuroglial tissue in the
      fibrocollagenous band; however, the stalk in cases 2 and 4 did not have glial
      fibrillary acidic protein-immunopositive neuroglial tissues. CONCLUSIONS:
      Therefore, the diagnosis of LDM should be made based on comprehensive evaluation
      of histologic and clinical findings.

PMID- 29063265
TI  - Method to perform safety stereotactic procedures in children under 2 years of
      age.
AB  - INTRODUCTION: Stereotactic procedures have been used in neurosurgery for many
      years. In children especially, care should be considered to avoid complication
      caused by fixation of the frame in a not fully developed skull bone. We present
      our method to adapt the frame in children under 2 years of age. METHODS: Twelve
      procedures in patients under 24 months were performed between 2003 and 2015.
      Micromar frame was used. It was adapted with a small pillow made of gauss
      attached to the posterior part to hold the head, then four pins were fixed
      without adjustment. We analyze for each patient age, indication, histopathology,
      and complications. RESULTS: Eleven patients with a mean age of 13.5 months (range
      9 to 22 months) underwent 12 stereotactic procedures. In all cases, biopsy
      samples were obtained, histopathology was positive in 11/12 cases. No
      complications occurred. CONCLUSION: Stereotactic frame procedures need special
      attention in small children where the skull bones are not fully developed. We
      present a simple method to perform this surgery in patients under 2 years of age.

PMID- 29063266
TI  - Congenital absence of the bilateral internal carotid artery: a review of the
      associated (ab)normalities from a newborn status to the eighth decade of life.
AB  - PURPOSE: Due to the fact that the internal carotid artery (ICA) is responsible
      for nourishing two thirds of the brain volume, our aim was to inspect the
      morphofunctional consequences of the bilateral lack of this artery. METHODS: In
      order to examine this condition, we referred to both the library archive of our
      Faculty of Medicine and electronic databases of anatomical and clinical reports
      that included the following keywords: "absence," "aplasia," or "agenesis" in
      combination with "internal carotid artery," "common carotid artery," or only
      "carotid artery." RESULT: We found 60 recorded cases of the bilateral ICA absence
      in the subjects of newborn status to the eighth decade of life, which had been
      discovered in 20 countries. The following ten parameters were described: the
      embryological base, terminology, history, incidence, general data, differential
      diagnosis, collateral circulation, the associated vascular aplasia and/or other
      variants, pathophysiology, and the importance in praxis. CONCLUSION: This review
      noted all the cases of the bilateral ICA aplasia published for the past 104
      years. Although there were 11.6% of cases of the associated cerebral aneurysms
      and 1-4 cases of 16 other diseases, approximately one quarter of the cases was
      without any pathology.

PMID- 29063267
TI  - Effect of post-nephrectomy acute kidney injury on renal outcome: a retrospective
      long-term study.
AB  - PURPOSE: The effects on renal prognosis of acute kidney injury after elective
      unilateral nephrectomy are ill-defined. We evaluated as whether post-operative
      acute kidney injury modifies renal outcome over the long term. METHODS: This is a
      retrospective study examining all consecutive adult patients referred to three
      Nephrology Units and that had previously undergone elective unilateral
      nephrectomy. We evaluated the association of post-nephrectomy acute kidney injury
      with the combined renal outcome of chronic dialysis requirement, >= 40% decline
      in glomerular filtration rate or new-onset severe proteinuria (> 500 mg/24 h).
      Clinical correlates of acute kidney injury and renal outcome were also examined.
      RESULTS: 106 patients were enrolled. 52 patients had post-operative acute kidney
      injury with a median increment of serum creatinine of 0.67 [0.48-0.86] mg/dl; in
      these patients, serum creatinine and urea increased from the first day post
      nephrectomy while contraction of urinary output was found in 7 patients. Older
      age [OR: 1.72; 95% CI 1.05-2.82; P = 0.030] associated with post-operative acute
      kidney injury. Over a median follow-up of 8.9 [95% CI 3.1-24.2] years, the
      combined renal outcome occurred, respectively, in 28 (53.8%) and 14 (25.9%)
      patients with and without acute kidney injury (P = 0.003). Logistic regression
      analysis showed that acute kidney injury (OR: 3.22; 95% CI 1.35-7.66; P = 0.008)
      and male gender (OR: 2.72; 95% CI 1.08-6.85; P = 0.034) were associated with poor
      renal outcome after adjustment for main comorbidities. CONCLUSIONS: In our
      population of referred patients, acute kidney injury after unilateral nephrectomy
      was common and associated with progressive chronic kidney disease, especially in
      older males.

PMID- 29063268
TI  - Radical prostatectomy or radiotherapy reduce prostate cancer mortality in elderly
      patients: a population-based propensity score adjusted analysis.
AB  - PURPOSE: Contemporary data regarding the effect of local treatment (LT) vs. non
      local treatment (NLT) on cancer-specific mortality (CSM) in elderly men with
      localized prostate cancer (PCa) are lacking. Hence, we evaluated CSM rates in a
      large population-based cohort of men with cT1-T2 PCa according to treatment type.
      METHODS: Within the SEER database (2004-2014), we identified 44,381 men >= 75
      years with cT1-T2 PCa. Radical prostatectomy and radiotherapy patients were
      matched and the resulting cohort (LT) was subsequently matched with NLT patients.
      Cumulative incidence and competing risks regression (CRR) tested CSM according to
      treatment type. Analyses were repeated after Gleason grade group (GGG)
      stratification: I (3 + 3), II (3 + 4), III (4 + 3), IV (8), and V (9-10).
      RESULTS: Overall, 4715 (50.0%) and 4715 (50.0%) men, respectively, underwent NLT
      and LT. Five and 7-year CSM rates for, respectively, NLT vs. LT patients were 3.0
      and 5.4% vs. 1.5 and 2.1% for GGG II, 4.5 and 7.2% vs. 2.5 and 2.8% for GGG III,
      7.1 and 10.0% vs. 3.5 and 5.1% for GGG IV, and 20.0 and 26.5% vs. 5.4 and 9.3%
      for GGG V patients. Separate multivariable CRR also showed higher CSM rates in
      NLT patients with GGG II [hazard ratio (HR) 3.3], GGG III (HR 2.6), GGG IV (HR
      2.4) and GGG V (HR 2.6), but not in GGG I patients (p = 0.5). CONCLUSIONS:
      Despite advanced age, LT provides clinically meaningful and statistically
      significant benefit relative to NLT. Such benefit was exclusively applied to GGG
      II to V but not to GGG I patients.

PMID- 29063270
TI  - Is the complete excision of circumferential intradural spinal meningiomas
      achievable?
AB  - BACKGROUND: Circumferential intradural spinal meningiomas are exceptionally rare.
      They pose several surgical challenges and a complete excision is not easy. The
      aim of this study is to provide surgical strategies to facilitate a full excision
      of such tumors. METHODS: A fully circumferential intradural meningioma at T9/10
      was fully removed via a posterior approach and a structured single procedure,
      with no intra or perioperative complications. CONCLUSIONS: Complete removal of
      circumferential spinal meningiomas can be achieved with wise preoperative
      planning, familiarity with techniques needed to transpose the spinal cord, and a
      structured staged excision of the four components of these tumors.

PMID- 29063269
TI  - Slow-metabolizing ADH1B and inactive heterozygous ALDH2 increase vulnerability to
      fatty liver in Japanese men with alcohol dependence.
AB  - BACKGROUND: Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B; rs1229984,
      His48Arg) and aldehyde dehydrogenase-2 (ALDH2; rs671, Glu504Lys) affect body
      weight, body fat, and lipid metabolism in individuals with alcohol dependence,
      and the aim of this study was to identify their determinants in relation to the
      development of fatty liver. METHODS: We evaluated associations between the
      presence of fatty liver and ADH1B and ALDH2 genotypes and other factors in 1604
      Japanese men who had been admitted for treatment of alcohol dependence. RESULTS:
      Fatty liver was diagnosed when ultrasonography showed both hepatorenal contrast
      and liver brightness. Age-adjusted usual alcohol intake did not differ according
      to ADH1B or ALDH2 genotypes. A multivariate analysis showed that the adjusted
      odds ratio (OR, 95% confidence interval) of slow-metabolizing ADH1B Arg/Arg
      carriers was 1.61 (1.27-2.03) for fatty liver and 1.82 (1.37-2.41) for fatty
      liver with deep attenuation in comparison with the ADH1B His/Arg or His/His
      carriers, and that the OR of inactive heterozygous ALDH2 Glu/Lys carriers was
      1.43 (1.08-1.91) for fatty liver and 1.84 (1.31-2.59) for fatty liver with deep
      attenuation in comparison with the ALDH2 Glu/Glu carriers. Younger age, shorter
      interval between the last drink and the ultrasound examination, larger body mass
      index, and absence of cirrhosis were identified as other positive determinants
      for fatty liver. CONCLUSIONS: The ADH1B Arg/Arg genotype and the ALDH2 Glu/Lys
      genotype were positive determinants of fatty liver in the subjects. These results
      suggest that slow ethanol and acetaldehyde metabolism accelerates the development
      of alcoholic fatty liver in heavy drinkers.

PMID- 29063271
TI  - Patients' beliefs about diagnosis and treatment of cervical spondylosis with
      radiculopathy.
AB  - BACKGROUND: The clinical results of surgical spine care may be influenced by the
      patients' understanding and knowledge of his or her condition, treatment options
      and decision-making process. The aim of this survey study was to evaluate certain
      beliefs and opinions of patients with a degenerative condition in the cervical
      spine with a history of cervical radiculopathy such as importance of magnetic
      resonance imaging, risk factors, treatment alternatives and effectiveness.
      METHODS: An anonymous questionnaire survey was performed on two different patient
      populations with a degenerative condition in the cervical spine with a history of
      cervical radiculopathy referred to the outpatients' clinics of two neurosurgical
      departments in Germany and Norway. The survey consisted of seven questions: four
      questions about the respondents' gender and age, history of previous spine
      surgery and/or conservative treatment for cervical disorder and three questions
      regarding the importance of imaging in the decision-making process, patients'
      willingness to undergo cervical surgery based on imaging findings even with few
      or no symptoms and the effectiveness of surgical or conservative treatment.
      RESULTS: Two hundred eleven patients answered the questionnaire. Sixty-seven
      percent of all patients with a degenerative cervical condition believe that
      results from MRI studies are more important than clinical findings. Forty-seven
      percent were willing to undergo surgery based on MRI showing abnormalities even
      without or having few symptoms. Fifty percent believe that surgery is more
      effective in the treatment of axial neck pain. CONCLUSION: Misbeliefs and
      misconceptions exist concerning certain aspects of the diagnosis and management
      in patients with degenerative conditions in the cervical spine with a history of
      cervical radiculopathy in a large proportion of patients referred to
      neurosurgical outpatient clinics.

PMID- 29063273
TI  - Clinical and radiological results of posterior cervical foraminotomy at two or
      three levels: a 3-year follow-up.
AB  - BACKGROUND: Single-level unilateral posterior cervical foraminotomy is regarded
      as a safe method. However, the outcomes of posterior cervical foraminotomy
      performed on two or three levels are uncertain and debated. We aimed to analyze
      the long-term clinical and radiological outcomes of posterior cervical
      foraminotomy at two or three levels. METHODS: From September 2008 to December
      2011, a total of 42 patients who underwent a posterior cervical foraminotomy at
      two or three levels and were followed for at least 3 years were analyzed with
      retrospective cohort study. Clinical assessments were performed using the visual
      analog scale (VAS), neck disability index (NDI) and modified MacNab criteria.
      Radiological evaluation included the assessment of static and dynamic lateral
      radiographs to identify instability, postlaminectomy kyphotic deformity, adjacent
      segmental degeneration (ASD), and focal degeneration. RESULTS: The mean VAS
      improved from preoperative score 8.5 +/- 0.3 to postoperative score 1.8 +/- 0.5
      significantly. The mean presenting NDI score was 32.9 +/- 2.0 and the mean
      postoperative NDI score was 14.2 +/- 1.3. Improvement of radiculopathy was
      displayed in 39 patients (92.9%). During radiological evaluation, no significant
      change in disc height related to ASD and focal degeneration was noted. However,
      we confirmed one patient with radiological instability and one patient with
      radiological postlaminectomy kyphotic deformity. CONCLUSIONS: Posterior cervical
      foraminotomy at two or three levels is fairly effective for treating patients
      with cervical radiculopathy, and results in long-lasting pain relief and improved
      quality of life in nearly all patients. However, further studies of three levels
      that include more patients are needed.

PMID- 29063272
TI  - The learning curve for endoscopic trans-sphenoidal resection of pituitary
      macroadenomas. A single institution experience, Leeds, UK.
AB  - BACKGROUND: The object of this study was to assess whether increasing operative
      experience results in greater endoscopic trans-sphenoidal resection of pituitary
      macroadenomas and lower complications. METHODS: A retrospective single
      institution cohort study was performed. Subjects underwent endoscopic trans
      sphenoidal resection of pituitary macroadenoma between July 2009 and July 2016 by
      three neurosurgeons. Following data collection, statistical analysis compared
      percentage of tumor resection and length of hospital stay (LOS) with experience.
      Complications including CSF leak are reported. RESULTS: In total, 142 patients
      (87 male, 55 female) mean age 55.1 were included. Surgeon 1 performed 106 cases;
      surgeon 2 performed 23 cases; and surgeon 3 performed 13 cases. Mean pre
      operative tumor volumes were 8.18 cm3, 6.52 cm3, and 3.47 cm3 and post-operative
      volumes were 2.21, 1.74, and 1.93 cm3 for surgeons 1, 2, and 3, respectively.
      Respective percentage resections were 74.3, 77.2, and 52.1%. Analysis
      demonstrated no difference in tumor resection with increasing experience for all
      three surgeons (p = 0.11, p = 0.17, and p = 0.26). Tumor consistency and
      cavernous sinus involvement did not appear to affect tumor resection. Mean LOS
      was 5 days, 4 days, and 3 days, respectively, with no significant correlation
      with experience for all three surgeons. Intraoperative CSF leak incidence was
      19/106 (18%) for surgeon 1, 6/23(26%) for surgeon 2, and 2/13(15%) for surgeon 3.
      Primary closure rate was 96.3% and only three other complications occurred.
      CONCLUSIONS: This study demonstrates that in our institution there is no
      statistically significant learning curve for the endoscopic resection of
      pituitary macroadenoma. However, there is a trend of improvement in tumor
      resection with experience for one surgeon. These findings suggest that the
      surgeons in our institution were capable of performing this procedure effectively
      with a low complication rate since adoption of the endoscopic technique in 2009.

PMID- 29063275
TI  - Intracellular Trafficking of Gonadotropin Receptors in Health and Disease.
AB  - Gonadotropin receptors belong to the highly conserved subfamily of the G protein
      coupled receptor (GPCR) superfamily, the so-called Rhodopsin-like family (class
      A), which is the largest class of GPCRs and currently a major drug target. Both
      the follicle-stimulating hormone receptor (FSHR) and the luteinizing
      hormone/chorionic gonadotropin hormone receptor (LHCGR) are mainly located in the
      gonads where they play key functions associated to essential reproductive
      functions. As any other protein, gonadotropin receptors must be properly folded
      into a mature tertiary conformation compatible with quaternary assembly and
      endoplasmic reticulum export to the cell surface plasma membrane. Several primary
      and secondary structural features, including presence of particular amino acid
      residues and short motifs and in addition, posttranslational modifications,
      regulate intracellular trafficking of gonadotropin receptors to the plasma
      membrane as well as internalization and recycling of the receptor back to the
      cell surface after activation by agonist. Inactivating mutations of gonadotropin
      receptors may derive from receptor misfolding and lead to absent or reduced
      plasma membrane expression of the altered receptor, thereby manifesting an array
      of phenotypical abnormalities mostly characterized by reproductive failure and/or
      abnormal or absence of development of secondary sex characteristics. In this
      chapter we review the structural requirements necessary for intracellular
      trafficking of the gonadotropin receptors, and describe how mutations in these
      receptors may lead to receptor misfolding and disease in humans.

PMID- 29063276
TI  - The Infamous, Famous Sulfonylureas and Cardiovascular Safety: Much Ado About
      Nothing?
AB  - PURPOSE OF REVIEW: Sulfonylureas (SUs) are one of the most commonly used glucose
      lowering agents worldwide. While their efficacy is undisputed, their
      cardiovascular safety has been debated since the 1970's. RECENT FINDINGS: With no
      dedicated cardiovascular studies to definitively answer this question,
      observational studies and meta-analyses abound and have reported divergent
      results, fueling the controversy. Studies that compared SUs to metformin or newer
      agents, like GLP-1 agonists and SGLT2 inhibitors, suggest a difference in
      cardiovascular events, yet this is likely the result of beneficial effects of the
      latter. Studies comparing SUs to other agents have been reassuring. SUs remain a
      common choice of treatment for patients with type 2 diabetes due to their
      exceptional value. They are effective at lowering glucose and thus contributing
      to the prevention of microvascular complications. Weight gain and hypoglycemia
      are their main side effects, although less severe when compared to insulin
      treatment. Their cardiovascular safety will remain a controversial topic due to
      lack of conclusive data, but there is no definitive evidence of harm with the
      second-generation agents.

PMID- 29063277
TI  - 3D-2D registration in endovascular image-guided surgery: evaluation of state-of
      the-art methods on cerebral angiograms.
AB  - PURPOSE: Image guidance for minimally invasive surgery is based on spatial co
      registration and fusion of 3D pre-interventional images and treatment plans with
      the 2D live intra-interventional images. The spatial co-registration or 3D-2D
      registration is the key enabling technology; however, the performance of state-of
      the-art automated methods is rather unclear as they have not been assessed under
      the same test conditions. Herein we perform a quantitative and comparative
      evaluation of ten state-of-the-art methods for 3D-2D registration on a public
      dataset of clinical angiograms. METHODS: Image database consisted of 3D and 2D
      angiograms of 25 patients undergoing treatment for cerebral aneurysms or
      arteriovenous malformations. On each of the datasets, highly accurate "gold
      standard" registrations of 3D and 2D images were established based on patient
      attached fiducial markers. The database was used to rigorously evaluate ten state
      of-the-art 3D-2D registration methods, namely two intensity-, two gradient-,
      three feature-based and three hybrid methods, both for registration of 3D pre
      interventional image to monoplane or biplane 2D images. RESULTS: Intensity-based
      methods were most accurate in all tests (0.3 mm). One of the hybrid methods was
      most robust with 98.75% of successful registrations (SR) and capture range of 18
      mm for registrations of 3D to biplane 2D angiograms. In general, registration
      accuracy was similar whether registration of 3D image was performed onto mono- or
      biplanar 2D images; however, the SR was substantially lower in case of 3D to
      monoplane 2D registration. Two feature-based and two hybrid methods had
      clinically feasible execution times in the order of a second. CONCLUSIONS:
      Performance of methods seems to fall below expectations in terms of robustness in
      case of registration of 3D to monoplane 2D images, while translation into
      clinical image guidance systems seems readily feasible for methods that perform
      registration of the 3D pre-interventional image onto biplanar intra
      interventional 2D images.

PMID- 29063274
TI  - Conserved Oligomeric Golgi and Neuronal Vesicular Trafficking.
AB  - The conserved oligomeric Golgi (COG) complex is an evolutionary conserved multi
      subunit vesicle tethering complex essential for the majority of Golgi apparatus
      functions: protein and lipid glycosylation and protein sorting. COG is present in
      neuronal cells, but the repertoire of COG function in different Golgi-like
      compartments is an enigma. Defects in COG subunits cause alteration of Golgi
      morphology, protein trafficking, and glycosylation resulting in human congenital
      disorders of glycosylation (CDG) type II. In this review we summarize and
      critically analyze recent advances in the function of Golgi and Golgi-like
      compartments in neuronal cells and functions and dysfunctions of the COG complex
      and its partner proteins.

PMID- 29063278
TI  - Relationships of relative humidity with PM2.5 and PM10 in the Yangtze River
      Delta, China.
AB  - Severe particulate matter (PM, including PM2.5 and PM10) pollution frequently
      impacts many cities in the Yangtze River Delta (YRD) in China, which has aroused
      growing concern. In this study, we examined the associations between relative
      humidity (RH) and PM pollution using the equal step-size statistical method. Our
      results revealed that RH had an inverted U-shaped relationship with PM2.5
      concentrations (peaking at RH = 45-70%), and an inverted V-shaped relationship
      (peaking at RH = 40 +/- 5%) with PM10, SO2, and NO2. The trends of polluted-day
      number significantly changed at RH = 70%. The very-dry (RH < 45%), dry (RH = 45
      60%) and low-humidity (RH = 60-70%) conditions positively affected PM2.5 and
      exerted an accumulation effect, while the mid-humidity (RH = 70-80%), high
      humidity (RH = 80-90%), and extreme-humidity (RH = 90-100%) conditions played a
      significant role in reducing particle concentrations. For PM10, the accumulation
      and reduction effects of RH were split at RH = 45%. Moreover, an upward slope in
      the PM2.5/PM10 ratio indicated that the accumulation effects from increasing RH
      were more intense on PM2.5 than on PM10, while the opposite was noticed for the
      reduction effects. Secondary transformations from SO2 and NO2 to sulfate and
      nitrate were mainly responsible for PM2.5 pollution, and thus, controlling these
      precursors is effective in mitigating the PM pollution in the YRD, especially
      during winter. The conclusions in this study will be helpful for regional air
      quality management.

PMID- 29063279
TI  - Clinical Application of Genetic Testing in Heart Failure.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present our current
      understanding of the genetic etiologies that may cause or predispose to heart
      failure. We highlight known phenotypes for which a genetic evaluation has
      clinical utility. RECENT FINDINGS: The literature continues to demonstrate and
      confirm a genetic basis for conditions that cause heart failure. Evidence
      suggests a genetic model involving rare and common variants of strong or weak
      effect, in combination with environmental factors that may manifest as familial
      or simplex disease. Clinical genetic testing is available for several phenotypes,
      which can aid in the diagnosis and identification of at-risk family members. The
      evaluation of heart failure should include investigating etiologies with a
      genetic basis. Conducting a genetic evaluation in patients with heart failure
      requires the ability to identify possible genetic etiologies in an individual's
      phenotype, obtain relevant family history, and clinically interpret genetic
      testing results.

PMID- 29063280
TI  - Pulmonary Hypertension Due to Left Ventricular Cardiomyopathy: Is it the Result
      or Cause of Disease Progression?
AB  - PURPOSE OF REVIEW: The purpose of this review is to define pulmonary hypertension
      in the setting of left heart disease (PH-LHD), discuss its epidemiology and
      pathophysiology, and highlight the cause and effect relationship it has with
      disease progression in the setting of cardiomyopathy. RECENT FINDINGS: Both
      pulmonary hypertension (PH) and heart failure are becoming increasingly common.
      As such, PH-LHD is now the most common form of PH. The pathophysiology of the
      condition relates to backward transmission of elevated left ventricular filling
      pressures into the pulmonary circulation and, ultimately, right ventricular (RV)
      strain/dysfunction. It is evident that these pathophysiologic processes are both
      the effect and cause of left heart disease progression. In this review, we
      describe the complex relationship between disease progression in left ventricular
      cardiomyopathy and PH-LHD. Clinicians and researchers should take note of the
      importance of PH-LHD and RV dysfunction to appropriately risk stratify patients
      and develop therapies for the condition.

PMID- 29063281
TI  - Identification and characterization of aldehyde oxidases (AOXs) in the cotton
      bollworm.
AB  - Aldehyde oxidases (AOXs) are a family of metabolic enzymes that oxidize aldehydes
      into carboxylic acids; therefore, they play critical roles in detoxification and
      degradation of chemicals. By using transcriptomic and genomic approaches, we
      successfully identified six putative AOX genes (HarmAOX1-6) from cotton bollworm,
      Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae). In silico expression
      profile, reverse transcription (RT)-PCR, and quantitative PCR (qPCR) analyses
      showed that HarmAOX1 is highly expressed in adult antennae, tarsi, and larval
      mouthparts, so they may play an important role in degrading plant-derived
      compounds. HarmAOX2 is highly and specifically expressed in adult antennae,
      suggesting a candidate pheromone-degrading enzyme (PDE) to inactivate the sex
      pheromone components (Z)-11-hexadecenal and (Z)-9-hexadecenal. RNA sequencing
      data further demonstrated that a number of host plants they feed on could
      significantly upregulate the expression levels of HarmAOX1 in larvae. This study
      improves our understanding of insect aldehyde oxidases and insect-plant
      interactions.

PMID- 29063282
TI  - Pressure-induced improvement in symmetry and change in electronic properties of
      SnSe.
AB  - To explore the structural and electronic properties of SnSe under pressure, we
      applied hydrostatic pressure from 0 to 8 GPa to a fully relaxed SnSe cell sample
      based on plane-wave pseudopotential density functional theory. The calculated
      results indicate that the structure of SnSe changes gradually from an irregular
      zigzag structure with low symmetry to a B1-like structure with regular
      arrangement and high symmetry under pressure. The lattice parameters and cell
      volume of SnSe decrease monotonically as the applied pressure increases. The
      energy band gap of SnSe becomes narrow under pressure and is finally closed at
      6.1 GPa. Moreover, we found that SnSe exhibits non-magnetic and semi-metallic
      features based on analyzing its electronic state density and spin state density.
      This can be attributed to the decrease in the lattices constants and the
      enhancement of the Sn-Se bond interaction under pressure, which causes the
      density of electronic states to increase near the Fermi surface. Finally, the
      charge distribution between Se-Sn-Se along the c-axis changes gradually from
      asymmetric to symmetric as the pressure is increased to 6.1 GPa and beyond. This
      implies that enhancement of the structure symmetry of SnSe can lead to a
      symmetrical distribution of charges, which further affects the bonding
      characteristics of the Sn-Se bond.

PMID- 29063283
TI  - [Prosthesis replacement in periprosthetic humeral fractures].
AB  - OBJECTIVE: Stabilization of the humerus with preservation or restoration of the
      shoulder function. INDICATIONS: Always in the presence of a loose prosthesis. It
      may become necessary in conditions of poor bone stock and if osteosynthesis is
      not possible. CONTRAINDICATIONS: Noncompliant patients due to alcohol or drugs.
      Local infections. SURGICAL TECHNIQUE: The loose implant is removed using an
      extended anterior deltopectoral approach. After exploration of the fracture and
      extended soft tissue release, the glenoidal components are implanted with
      visualization and protection of the axillary nerve. A long stemmed implant is
      typically needed on the humeral side. It is anchored in the distal fragment over
      a length of about 6 cm. Soft tissue tension is crucial, especially with reverse
      shoulder arthroplasty. POSTOPERATIVE MANAGEMENT: Postoperatively, the affected
      limb is immobilized for 6 weeks on a 15 degrees  shoulder abduction pillow with
      active assisted movement therapy up to the horizontal plane. This is followed by
      gradual pain-adapted increases of movement, muscle coordination, and strength.
      RESULTS: In 17 patients with periprosthetic fractures of the humerus surgically
      treated in our institution, 4 underwent revision arthroplasty because of a loose
      prosthesis. No intra- or postoperative complications were observed. All fractures
      healed except one.

PMID- 29063284
TI  - Androgen receptors and muscle: a key mechanism underlying life history trade
      offs.
AB  - Sexual dimorphism in skeletal muscle is prominent in mammals, with males
      typically having larger and stronger muscles than females. Furthermore,
      neuromuscular systems with sexual functions are remarkably sexually dimorphic in
      a wide variety of vertebrates. Endocrine mechanisms are of central importance for
      sexual differentiation of these traits, and anabolic actions of gonadal
      testosterone have been intensively studied. Here we review the relationship
      between androgen receptor (AR) and sexual differentiation of neuromuscular
      systems. We focus our review on the hypotheses that sexual dimorphism and
      androgen responsiveness of neuromuscular systems is a function of the amount of
      AR expressed by muscle and that AR in muscle is a key mechanism on which
      evolution acts to shape individual and species differences in reproductive
      behavior.

PMID- 29063286
TI  - Nitrite administration improves sepsis-induced myocardial and mitochondrial
      dysfunction by modulating stress signal responses.
AB  - PURPOSE: A specific therapeutic strategy in sepsis-induced myocardial dysfunction
      remains to be determined. Nitrite may have cardioprotective effects against
      sepsis-induced myocardial dysfunction. This study investigated the
      cardioprotective effects of nitrite on myocardial function, mitochondrial
      bioenergetics, and its underlying molecular mechanisms in severe septic rats.
      METHODS: Sepsis was induced in male Wistar rats by cecal ligation and puncture
      (CLP). After CLP, we administered normal saline (NS group) or nitrite (nitrite
      group) subcutaneously. We administered nitrite at different doses (0.1-10 mg/kg)
      to ascertain the most effective dose and examined cardiac function in an isolated
      heart experiment 8 h after CLP. We investigated mitochondrial bioenergetics and
      molecular mechanisms underlying the administration of nitrite in vitro. RESULTS:
      In isolated heart experiments, the left ventricular developed pressure (96 +/- 5
      mmHg) at a moderate nitrite dose (1.0 mg/kg) was significantly higher than that
      in the NS group (75 +/- 4 mmHg, P < 0.05). Mitochondrial oxidative
      phosphorylation in the nitrite group was significantly higher than that in the NS
      group (P < 0.01). Immunoblotting revealed that nitrite significantly increased
      the phosphorylation of Akt (P < 0.05) and reduced the nuclear translocation of NF
      kappaB (P < 0.05) compared with the NS group. Nitrite was also shown to improve
      the rate of survival in severe septic rats (P < 0.001). CONCLUSIONS: Our results
      showed that a moderate nitrite dose improved septic myocardial dysfunction at
      organ, cellular, and molecular levels via modulation of stress signal responses,
      which resulted in an improvement in survival.

PMID- 29063287
TI  - Characterization of a mildly alkalophilic and thermostable recombinant Thermus
      thermophilus laccase with applications in decolourization of dyes.
AB  - OBJECTIVE: To examine the potential for applications of TthLAC, a monomeric (~ 53
      kDa) laccase encoded by the genome of Thermus thermophilus (strain HB 27) which
      can be produced at low cost in Escherichia coli. RESULT: Functional, thermostable
      and mildly alkalophilic TthLAC of high purity (> 90%) was produced through simple
      heating of suspended (TthLAC overexpressing) E.coli cells at 65  degrees C. For
      reactions of short duration (< 1 h) the temperature for optimal activity is ~ 90 
      degrees C. However, TthLAC undergoes slow partial unfolding and thermal
      inactivation above 65  degrees C, making it unsuitable for long incubations above
      this temperature. With different substrates, optimal function was observed from
      pH 6 to 8. With the substrate, ABTS, catalytic efficiency (K m) and maximum
      velocity (Vmax) at 60  degrees C and pH 6.0 were determined to be 2.4 * 103 uM
      and 0.04 * 103 uM/min respectively. Ultra-pure, affinity-purified TthLAC was used
      to confirm and characterize the enzyme's ability to oxidize known (laccase)
      substrates such as ABTS, syringaldazine and 4-fluoro-2-methylphenol. TthLAC
      decoloured up to six different industrial dyes, with or without the use of redox
      mediators such as ABTS. CONCLUSIONS: Unlike versatile laccases from most other
      sources, which tend to be thermolabile as well as acidophilic, TthLAC is a
      versatile, thermostable, mildly alkalophilic laccase which can be produced at low
      cost in E.coli for various redox applications.

PMID- 29063285
TI  - Songbird chemical signals reflect uropygial gland androgen sensitivity and
      predict aggression: implications for the role of the periphery in chemosignaling.
AB  - Chemical signals can provide useful information to potential mates and rivals.
      The production mechanisms of these signals are poorly understood in birds,
      despite emerging evidence that volatile compounds from preen oil may serve as
      chemosignals. Steroid hormones, including testosterone (T), may influence the
      production of these signals, yet variation in circulating T only partly accounts
      for this variation. We hypothesized that odor is a T-mediated signal of an
      individual's phenotype, regulated in part by androgen sensitivity in the
      uropygial gland. We quantified natural variation in chemosignals, T, uropygial
      gland androgen sensitivity, and aggressive behavior in dark-eyed juncos (Junco
      hyemalis). The interaction between circulating T and androgen receptor transcript
      abundance significantly correlated with volatile concentrations in male, but not
      female, preen oil. In both sexes, odorant variables correlated with aggressive
      response to an intruder. Our results suggest that preen oil volatiles could
      function as signals of aggressive intent, and, at least in males, may be
      regulated by local androgen receptor signaling in the uropygial gland. Because
      these behavioral and chemical traits have been linked with reproductive success,
      local regulation of androgen sensitivity in the periphery has the potential to be
      a target of selection in the evolution of avian olfactory signaling.

PMID- 29063288
TI  - Development of RNA aptamer that inhibits methyltransferase activity of dengue
      virus.
AB  - OBJECTIVES: To develop an RNA aptamer specific for the methyltransferase (MTase)
      of dengue virus (DENV) which is essential for viral genome replication and
      translation acting directly on N-7 and 2'-O-methylation of the type-I cap
      structure of the viral RNA. RESULTS: We identified 2'-fluoro-modified RNA
      aptamers that can specifically bind DENV serotype 2 (DENV2) MTase using
      systematic evolution of ligands by exponential enrichment technology. We
      truncated the chosen aptamer into a 45-mer RNA sequence that can bind DENV2 MTase
      with K d  ~ 28 nM and inhibit N-7 methylation activity of the protein. Moreover,
      the 45-mer truncated aptamer could not only bind with an K d  ~ 15.6 nM but also
      inhibit methylation activity of DENV serotype 3 (DENV3) MTase. The 45-mer aptamer
      competitively impeded binding of both DENV2 and DENV3 genomic RNA to MTase of
      each serotype. CONCLUSION: The selected 45-mer truncated RNA aptamer specifically
      and avidly bound DENV MTase and competitively inhibited its methylation activity,
      and thus could be useful for the development of anti-DENV agents.

PMID- 29063291
TI  - Predictive factors of drug-resistant epilepsy in children presenting under 2
      years of age: experience of a tertiary center in Turkey.
AB  - Population-based studies report that children with epilepsy have relatively
      better prognosis than those with an onset at infancy, though studies about this
      period are limited. We aimed to evaluate the etiology in infant epilepsy less
      than 2 years of age and foreseeable risk factors for anti-epileptic drug
      resistance. We evaluated the patients who were presented to the division of
      pediatric neurology in our university hospital with seizures when they were
      between 1 and 24 months of age and diagnosed as epilepsy. Two hundred and twenty
      nine patients (110 male and 119 female) who were diagnosed between the ages of 1
      24 months were included in the study. The etiologies were structural (n =
      55;24%), genetic (n = 29;12.7%), metabolic (n = 27;11.7%), and infectious (n =
      8;3.5%), and it was unknown in 110 patients (48%). One-hundred and forty (61%)
      patients met the criteria for drug-resistant epilepsy (DRE). Multivariate
      logistic regression analysis showed that developmental delay at onset (OR 3.9,
      95% CI 1.22, 12.47, p = 0.021), multifocal epileptiform discharges (OR 2.8, 95%
      CI 1.1, 7.44, p = 0.031), and history of status epilepticus (OR 32.9, 95% CI 3.8,
      285.35, p = 0.001) were strong predictive factors for DRE. The epilepsy in
      children under 2 years of age is highly resistant to the anti-epileptic drugs,
      which could be related to the history of status epilepticus, developmental delay
      at onset, and multifocal epileptiform discharges.

PMID- 29063290
TI  - Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral
      Uterine Artery Remodelling.
AB  - PURPOSE OF REVIEW: The aim of the study is to perform a critical assessment of in
      vitro models of pre-eclampsia using complementary human and cell line-based
      studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling
      and trophoblast functionality will also be discussed. RECENT FINDINGS: A number
      of proteins and microRNAs have been implicated as key in SUA remodelling, which
      could be explored as early biomarkers or therapeutic targets for prevention of
      pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells,
      endothelial cells, immune cells and placental tissue were discussed to elucidate
      the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a
      multifactorial disease, and the mechanisms involved in its pathogenesis are
      complex and still largely unknown. Further studies are required to provide better
      understanding of the key processes leading to inappropriate placental development
      which is the root cause of pre-eclampsia. This new knowledge could identify novel
      biomarkers and treatment strategies.

PMID- 29063289
TI  - Salsolinol: an Unintelligible and Double-Faced Molecule-Lessons Learned from In
      Vivo and In Vitro Experiments.
AB  - Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a
      tetrahydroisoquinoline derivative whose presence in humans was first detected in
      the urine of Parkinsonian patients on L-DOPA (L-dihydroxyphenylalanine)
      medication. Thus far, multiple hypotheses regarding its
      physiological/pathophysiological roles have been proposed, especially related to
      Parkinson's disease or alcohol addiction. The aim of this review was to outline
      studies related to salsolinol, with special focus on in vivo and in vitro
      experimental models. To begin with, the chemical structure of salsolinol together
      with its biochemical implications and the role in neurotransmission are
      discussed. Numerous experimental studies are summarized in tables and the most
      relevant ones are stressed. Finally, the ability of salsolinol to cross the blood
      brain barrier and its possible double-faced neurobiological potential are
      reviewed.

PMID- 29063293
TI  - Two mTOR inhibitors, rapamycin and Torin 1, differentially regulate iron-induced
      generation of mitochondrial ROS.
AB  - It is generally believed that gene-environment interaction may contribute to
      neurodegeneration. Of particular note is that iron overload may be one of the
      risk factors for neurodegeneration. However, the mechanisms underlying iron
      associated neurotoxicity are not fully understood. Here we explored the effects
      of mechanistic target of rapamycin (mTOR) inhibition in iron-stressed human
      neuroblastoma cells. Two mTOR inhibitors, rapamycin and Torin 1, had similar
      effects in cells exposed to a relatively low concentration of iron. At a higher
      concentration of iron, Torin 1, instead of rapamycin, could further aggravate
      iron-induced cytotoxicity, and mitochondrial ROS levels were significantly higher
      in Torin 1-treated cells. These results suggest that mTOR inhibition may not be
      able to alleviate iron-induced neurotoxicity.

PMID- 29063294
TI  - Erratum to: Phase 1 study of darolutamide (ODM-201), a new-generation androgen
      receptor antagonist, in Japanese patients with metastatic castration-resistant
      prostate cancer.

PMID- 29063295
TI  - Long-Term Outcomes After R0 Resection of Synchronous Peritoneal Metastasis from
      Colorectal Cancer Without Cytoreductive Surgery or Hyperthermic Intraperitoneal
      Chemotherapy.
AB  - BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines for colon
      cancer recently added the following footnote regarding the therapeutic strategy
      for peritoneal metastases: "If R0 resection can be achieved, surgical resection
      of isolated peritoneal disease may be considered at experienced centers." This
      study investigated the efficacy of R0 resection of peritoneal metastasis from
      colorectal cancer without cytoreductive surgery or hyperthermic intraperitoneal
      chemotherapy (HIPEC). METHODS: This retrospective cohort study was conducted at a
      single-institution tertiary care cancer center. Among 496 consecutive M1c
      colorectal cancer patients, R0 resection was achieved for 94 patients (19%). The
      subjects were 78 consecutive patients with colorectal cancer and simultaneous
      peritoneal metastasis but no other distant metastases who underwent R0 resection
      at the National Cancer Center Hospital from 1971 to 2016 (16% of all M1c
      patients). Overall survival (OS) was investigated, and clinicopathologic
      variables were analyzed for prognostic significance. RESULTS: No perioperative
      mortality was noted. The 3-year OS rate was 45%, and the 5-year OS rate was
      28.7%. The median survival time was 33.4 months. Notably, 17 patients survived
      for more than 5 years, and 9 of these patients did not receive any chemotherapy.
      Multivariate analysis showed cancer location in the colon and harvesting of 12 or
      more lymph nodes to be independent factors associated with a better prognosis.
      CONCLUSIONS: From the perspective of long-term outcomes and no perioperative
      mortality, R0 resection of peritoneal metastasis from colorectal cancer, without
      complete peritonectomy or HIPEC, appeared to be an acceptable therapeutic option
      for some patients with peritoneal metastasis.

PMID- 29063292
TI  - The six metal binding domains in human copper transporter, ATP7B: molecular
      biophysics and disease-causing mutations.
AB  - Wilson Disease (WD) is a hereditary genetic disorder, which coincides with a
      dysfunctional copper (Cu) metabolism caused by mutations in ATP7B, a membrane
      bound P1B-type ATPase responsible for Cu export from hepatic cells. The N
      terminal part (~ 600 residues) of the multi-domain 1400-residue ATP7B constitutes
      six metal binding domains (MBDs), each of which can bind a copper ion, interact
      with other ATP7B domains as well as with different proteins. Although the ATP7B's
      MBDs have been investigated in vitro and in vivo intensively, it remains unclear
      how these domains modulate overall structure, dynamics, stability and function of
      ATP7B. The presence of six MBDs is unique to mammalian ATP7B homologs, and many
      WD causing missense mutations are found in these domains. Here, we have
      summarized previously reported in vitro biophysical data on the MBDs of ATP7B and
      WD point mutations located in these domains. Besides the demonstration of where
      the research field stands today, this review showcasts the need for further
      biophysical investigation about the roles of MBDs in ATP7B function. Molecular
      mechanisms of ATP7B are important not only in the development of new WD treatment
      but also for other aspects of human physiology where Cu transport plays a role.

PMID- 29063296
TI  - Surgical Resection Does Not Improve Survival in Multifocal Intrahepatic
      Cholangiocarcinoma: A Comparison of Surgical Resection with Intra-Arterial
      Therapies.
AB  - BACKGROUND: Multifocal intrahepatic cholangiocarcinoma (ICC) has traditionally
      been treated with surgical resection when amenable. Intra-arterial therapy (IAT)
      for multifocal ICC has not been directly compared with surgical resection.
      METHODS: A single-center, retrospective review of consecutive patients treated
      for multifocal ICC was conducted. Patients with distant metastases or treatment
      with systemic chemotherapy alone were excluded. Patients were divided into two
      groups: surgical resection versus IAT; IAT included transarterial
      chemoembolization (TACE), transarterial radioembolization (TARE), and hepatic
      arterial infusion (HAI) pump therapy. Subjects were also analyzed by surgical
      resection, TACE, and HAI pump therapy. RESULTS: Overall, 116 patients with
      multifocal ICC were studied, 57 in the surgical resection group and 59 in the IAT
      group (TACE = 41, HAI pump = 16, TARE = 2). The IAT group was characterized by a
      higher incidence of bilobar disease (88.1% vs. 47.4%, p < 0.001), larger tumors
      (median 10.6 vs. 7.5 cm, p = 0.004), higher incidence of macrovascular invasion
      (44.1% vs. 24.6%, p = 0.027), and higher rate of nodal metastases (57.6% vs.
      28.6%, p = 0.002). Median overall survival for surgical resection was 20 months
      versus 16 months for IAT (p = 0.627). Multivariate analysis found that
      macrovascular invasion [hazard ratio (HR) 2.52, 95% confidence interval (CI) 1.56
      4.09] and non-receipt of systemic chemotherapy (HR 3.81, 95% CI 2.23-6.52) were
      independent poor prognostic risk factors. Surgical resection was not associated
      with a survival advantage over IAT on multivariate analysis (p = 0.242).
      CONCLUSION: Despite selection bias for use of surgical resection compared with
      IAT, no survival advantage was conferred in the treatment of multifocal ICC.

PMID- 29063297
TI  - Pre-operative Axillary Ultrasound-Guided Needle Sampling in Breast Cancer:
      Comparing the Sensitivity of Fine Needle Aspiration Cytology and Core Needle
      Biopsy.
AB  - BACKGROUND: Pre-operative ultrasound-guided needle sampling (UNS) of abnormal
      axillary lymph nodes in breast cancer can identify patients with axillary
      metastases and therefore rationalize patient care and inform decision-making. To
      obtain tissue diagnosis, UNS can be performed by either fine needle aspiration
      (FNA) or core needle biopsy (CNB). However, few studies have compared the
      sensitivity of these techniques and the majority show no difference. METHODS: All
      node-positive patients (those with micro- and macrometastases but not isolated
      tumor cells) treated at a tertiary referral center between January 2012 and
      December 2015 were retrospectively identified from pathology records. The result
      of the first axillary UNS performed on each patient was compared with
      postoperative histopathology results. The UNS method used was according to
      individual radiologist preference. RESULTS: A total of 215 patients underwent FNA
      (1 patient had bilateral breast cancer and underwent bilateral FNA), and 92
      underwent CNB. Sensitivity of CNB was significantly higher than FNA (83.7 vs.
      69.0%, P = 0.008). The false-negative rate in the FNA group was therefore higher
      than in the CNB group by a factor of 2.5. There was no difference in inadequacy
      rate between the two techniques. There were no complications in the FNA group,
      and only one hematoma (which did not require operative intervention) in the CNB
      group. CONCLUSIONS: CNB is safe and should be the preferred technique for UNS to
      improve sensitivity.

PMID- 29063298
TI  - Four-Dimensional Computed Tomography: Clinical Impact for Patients with Primary
      Hyperparathyroidism.
AB  - BACKGROUND: In recent years, four-dimensional computed tomography (4DCT) has
      emerged as a new localization study for primary hyperparathyroidism (pHPT).
      OBJECTIVE: We aimed to assess the added value of 4DCT in our institution in the
      first 4 years of use. METHODS: A retrospective cohort study was conducted from
      February 2004 to June 2015. Since 2011, patients over 50 years of age without
      concordant sestamibi-SPECT (SeS) and ultrasound (US) findings underwent 4DCT.
      Imaging results, surgical findings, histopathology, and postoperative
      biochemistry were collected. RESULTS: A total of 536 parathyroid operations in
      510 patients were performed during the study period. The overall cure rate was
      99.2% after reoperation in some patients, and the overall sensitivity for SeS was
      76.0%, and 74.8% for US. Since 2011, 100 patients without concordant SeS/US
      findings have undergone 4DCT, with a sensitivity of 72.9%. This is in comparison
      to the sensitivities for SeS (48.3%) and US (52.3%). 4DCT was more sensitive in
      patients with persistent/recurrent disease (60.0% compared with SeS 43.8% and US
      36.4%) and patients with multigland disease (67.4% compared with SeS 40.9% and US
      42.1%). Comparison between outcomes in the pre- versus post-CT era demonstrated
      no difference in the initial cure rate (95.4 vs. 95.9%, p = 0.85) or the rate of
      minimally invasive parathyroidectomies (74.5 vs. 79.9%, p = 0.22). CONCLUSION:
      Parathyroid 4DCT can aid surgical planning in cases without concordant SeS/US
      findings; however, the introduction of 4DCT as a second-line test did not change
      our overall cure rate or rate of minimally invasive parathyroidectomy. The role
      of 4DCT as the primary localization study for pHPT merits further investigation.

PMID- 29063299
TI  - Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Surgical
      Resection of Pancreatic Ductal Adenocarcinoma Appears to be Safe and Effective.
AB  - BACKGROUND: A standardized treatment regimen for unresectable isolated local
      recurrence (ILR) of pancreatic ductal adenocarcinoma has not been established.
      This study evaluated the outcomes for patients with ILR who underwent
      stereotactic body radiation therapy (SBRT). METHODS: The records of patients with
      ILR who underwent SBRT between 2010 and 2016 were retrospectively reviewed.
      Symptom palliation and treatment-related toxicity were recorded. Associations
      between patient or treatment characteristics and overall survival (OS),
      progression-free survival (PFS), and local progression-free survival (LPFS) were
      assessed. RESULTS: The study identified 51 patients who received SBRT for ILR. Of
      the 51 patients, 26 (51%) had not received radiation therapy before SBRT. The
      median OS was 36 months after diagnosis. From the first day of SBRT, the median
      OS, PFS, and LPFS were respectively 16, 7, and 10 months. Patients with a
      recurrence-free interval of 9 months or longer after surgery had superior OS (P =
      0.019). Maintenance chemotherapy after SBRT was associated with superior OS (P <
      0.001) and LPFS (P = 0.027). In the multivariable analysis, poorly differentiated
      tumor grade [hazard ratio (HR) 11.274], positive surgical margins (HR 0.126), and
      reception of maintenance chemotherapy (HR 0.141) were independently associated
      with OS. Positive surgical margins (HR 0.255) and maintenance chemotherapy (HR
      0.299) were associated with improved LPFS. Of 16 patients, 10 (63%) experienced
      abdominal pain relief after SBRT. Four patients (8%) experienced grade 3
      gastrointestinal toxicity, and one patient experienced grade 4 gastrointestinal
      toxicity. CONCLUSIONS: Use of SBRT for ILR improved pain for a majority of the
      patients with acceptable acute and late toxicity. The findings show that SBRT is
      a feasible treatment for select patients with ILR. For those who receive SBRT,
      maintenance chemotherapy should be considered.

PMID- 29063301
TI  - Significance of a frozen section analysis of the ureteral margin in bladder
      cancer patients treated with radical cystectomy and neoadjuvant chemotherapy.
AB  - Although the clinical utility of a frozen section analysis (FSA) at the time of
      radical cystectomy (RC) has already been established, its significance and
      utility in bladder cancer patients receiving neoadjuvant chemotherapy (NAC) have
      not yet been fully evaluated. We identified 458 patients (937 ureters) who
      underwent open RC for bladder cancer at our 7 Japanese institutions between 2004
      and 2015. Among these patients, 139 (284 ureters) received NAC before RC (NAC
      group), while 319 (653 ureters) underwent RC alone (non-NAC group). FSA was
      performed on 356 out of 937 (38.0%) ureters and 179 out of 458 (39.1%) patients.
      FSA was positive in 30 out of 356 (8.4%) ureters and its sensitivity,
      specificity, and accuracy were 89.3, 98.5, and 97.8%, respectively. In the NAC
      group, FSA was performed on 138 out of 284 (48.6%) ureters and 68 out of 139
      (48.9%) patients. FSA was positive in 8 out of 138 ureters (5.8%), and its
      sensitivity, specificity, and accuracy were 77.8, 99.2, and 97.8%, respectively.
      In the non-NAC group, FSA was performed on 218 out of 653 (33.4%) ureters and 111
      out of 319 (34.8%) patients. FSA was positive in 22 out of 218 (10.1%) ureters,
      and its sensitivity, specificity, and accuracy were 94.7, 98.0, and 97.7%,
      respectively. No correlation was observed between preoperative clinical factors
      and FSA positivity in the NAC group; however, in the non-NAC group, the incidence
      of FSA positivity in the ureters of patients with concomitant CIS in TUR-BT
      specimens was 8/41 (19.5%), which was significantly higher than that in their
      counterpart (14/177, 7.9%, p = 0.033). Even in the era of NAC in the management
      of bladder cancer patients, the performance of FSA does not change and FSA at the
      time of RC may provide useful diagnostic information.

PMID- 29063303
TI  - Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA
      with PET Imaging.
AB  - PURPOSE: Determining the glomerular filtration rate (GFR) is essential for
      clinical medicine but also for pre-clinical animal studies. Functional imaging
      using positron emission tomography (PET) allows repetitive almost non-invasive
      measurements. The aim of the study was the development and evaluation of easily
      synthesizable PET tracers for GFR measurements in small animals. PROCEDURES:
      Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid
      (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins
      was tested in vitro. The distribution of the tracers in rats was analyzed by PET
      imaging and ex vivo measurements. From the time-activity-curve of the blood
      compartment (heart) and the total tracer mass excreted by the kidney, the GFR was
      calculated. These values were compared directly with the inulin clearance in the
      same animals. RESULTS: Both tracers did not bind to blood cells. [68Ga]DPTA but
      not [68Ga]EDTA showed strong binding to plasma proteins. For this reason,
      [68Ga]DPTA stayed much longer in the blood and only 30 % of the injected dose was
      eliminated by the kidney within 60 min whereas the excretion of [68Ga]EDTA was 89
      +/- 1 %. The calculated GFR using [68Ga]EDTA was comparable to the measured
      inulin clearance in the same animal. Using [68Ga]-DPTA, the measurements led to
      values which were 80 % below the normal GFR. The results also revealed that
      definition of the volume of interest for the blood compartment affects the
      calculation and may lead to a slight overestimation of the GFR. CONCLUSIONS:
      [68Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small
      animals. It is easy to be labeled, and the results are in good accordance with
      the inulin clearance. [68Ga]DTPA led to a marked underestimation of GFR due to
      its strong binding to plasma proteins and is therefore not an appropriate tracer
      for GFR measurements.

PMID- 29063302
TI  - Effects of tolvaptan on urine output in hospitalized heart failure patients with
      hypoalbuminemia or proteinuria.
AB  - Hypoalbuminemia is an independent prognostic factor in hospitalization for heart
      failure (HHF). Hypoalbuminemia or proteinuria is related to resistance to loop
      diuretics. Tolvaptan is an oral non-peptide, competitive antagonist of
      vasopressin receptor-2. It has been used for the treatment of volume overload in
      HHF patients in several Asian countries. Several studies have demonstrated marked
      improvement in congestion in HHF patients. However, whether tolvaptan is useful
      for HHF patients with hypoalbuminemia or proteinuria (both of which are related
      to resistance to loop diuretics) has not been clarified. We examined the diuretic
      response to tolvaptan in HHF patients with hypoalbuminemia or proteinuria. We
      defined hypoalbuminemia as a serum level of albumin < 2.6 g/dl. Fifty-one HHF
      patients who received additional tolvaptan upon therapies with loop diuretics
      were divided into the hypoalbuminemia group (n = 24) or control group (n = 27).
      The changes in urine output per day were not different between the two groups
      [610 (range 100-1032); 742 (505-1247) ml, P = 0.313]. There was no difference in
      diuretic responses between patients with and without proteinuria. The serum level
      of albumin did not correlate with changes in urine output per day after tolvaptan
      treatment (P = 0.276, r = 0.156). Thus, additional administration of tolvaptan
      elicited a good diuretic response in HHF patients with hypoalbuminemia or
      proteinuria. These data suggest that tolvaptan might be beneficial for such HHF
      patients.

PMID- 29063300
TI  - Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: Beyond Vasospasm and
      Towards a Multifactorial Pathophysiology.
AB  - PURPOSE OF REVIEW: Delayed cerebral ischemia (DCI) is common after subarachnoid
      hemorrhage (SAH) and represents a significant cause of poor functional outcome.
      DCI was mainly thought to be caused by cerebral vasospasm; however, recent
      clinical trials have been unable to confirm this hypothesis. Studies in humans
      and animal models have since supported the notion of a multifactorial
      pathophysiology of DCI. This review summarizes some of the main mechanisms under
      investigation including cerebral vascular dysregulation, microthrombosis,
      cortical spreading depolarizations, and neuroinflammation. RECENT FINDINGS:
      Recent guidelines have differentiated between DCI and angiographic vasospasm and
      have highlighted roles of the microvasculature, coagulation and fibrinolytic
      systems, cortical spreading depressions, and the contribution of the immune
      system to DCI. Many therapeutic interventions are underway in both preclinical
      and clinical studies to target these novel mechanisms as well as studies
      connecting these mechanisms to one another. Clinical trials to date have been
      largely unsuccessful at preventing or treating DCI after SAH. The only successful
      pharmacologic intervention is the calcium channel antagonist, nimodipine. Recent
      studies have provided evidence that cerebral vasospasm is not the sole
      contributor to DCI and that additional mechanisms may play equal if not more
      important roles.

PMID- 29063304
TI  - Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance
      with Gadolinium Enhancement and Added Value to [18F]FDG PET.
AB  - PURPOSE: The purpose of this study is to evaluate the diagnostic concordance and
      metric correlations of amide proton transfer (APT) imaging with gadolinium
      enhanced magnetic resonance imaging (MRI) and 2-deoxy-2-[18F-]fluoro-D-glucose
      ([18F]FDG) positron emission tomography (PET), using hybrid brain PET/MRI.
      PROCEDURES: Twenty-one subjects underwent brain gadolinium-enhanced [18F]FDG
      PET/MRI prospectively. Imaging accuracy was compared between unenhanced MRI, MRI
      with enhancement, APT-weighted (APTW) images, and PET based on six diagnostic
      criteria. Among tumors, the McNemar test was further used for concordance
      assessment between gadolinium-enhanced imaging, APT imaging, and [18F]FDG PET. As
      well, the relation of metrics between APT imaging and PET was analyzed by the
      Pearson correlation analysis. RESULTS: APT imaging and gadolinium-enhanced MRI
      showed superior and similar diagnostic accuracy. APTW signal intensity and
      gadolinium enhancement were concordant in 19 tumors (100 %), while high [18F]FDG
      avidity was shown in only 12 (63.2 %). For the metrics from APT imaging and PET,
      there was significant correlation for 13 hypermetabolic tumors (P < 0.05) and no
      correlation for the remaining six [18F]FDG-avid tumors. CONCLUSIONS: APT imaging
      can be used to increase diagnostic accuracy with no need to administer gadolinium
      chelates. APT imaging may provide an added value to [18F]FDG PET in the
      evaluation of tumor metabolic activity during brain PET/MR studies.

PMID- 29063305
TI  - Should alcohol screening be a routine practice in alcohol-related facial trauma
      care? A narrative review.
AB  - The link between alcohol intoxication and Emergency Department (ED) attendance
      for management of alcohol-related injuries has been well documented. The acute
      settings such as ED and surgical wards may not be the most appropriate
      environment for treatment of chronic conditions, but traumatic episode
      presentation to ED may offer the most opportunistic time to focus on screening
      against harmful alcohol use in order to provide timely feedback and support.
      Although ED provides an opportunity to identify patients with alcohol problems,
      the initial challenge is finding suitable ways to identify and screen affected
      patients. This paper is a narrative review on methods of alcohol screening and
      its effectiveness and efficacy in trauma care setting. It is second part in a
      series on implementation of screening and brief intervention in managing trauma
      patients.

PMID- 29063306
TI  - What happens to biliary colic patients in New York State? 10-year follow-up from
      emergency department visits.
AB  - INTRODUCTION: Biliary colic is a common diagnosis for patients presenting to the
      emergency department (ED). The purpose of this study is to examine the outcomes
      of patients coming to the ED with biliary colic. METHODS: The NYS longitudinal
      SPARCS database was used to identify patients presenting to the ED with biliary
      colic from 2005 to 2014. Through the use of a unique identifier, patients were
      followed in NYS across multiple institutions. Patients who were lost to follow
      up, with duplicated records, and those that underwent percutaneous
      cholecystectomy tubes were excluded from the analysis. RESULTS: Between 2005 and
      2014, there were 72,376 patients who presented to an ED with biliary colic. The
      admission rate was 20.7-26.02%. Overall, most patients who presented to the ED
      did not undergo surgery (39,567, 54.7%), of which 35,204 (89%) had only one ED
      visit, while 4,363(11%) returned to the ED (>= 2 visits). Only 3.23-5.51% of
      patients underwent cholecystectomy at the time of initial presentation. Most
      subsequent cholecystectomies were performed electively (27.38-52.51%) (See Table
      1 in this article). Average time to surgery among patients with elective
      cholecystectomy was 178.4 days. From the patients who underwent cholecystectomy,
      10.35% had cholecystectomy at their first ED visit, 77.7% had cholecystectomy
      following the first ED visit, and 12% had multiple ED visits prior to surgery.
      Among patients who were discharged from the ED, 32% had their surgery at a
      different hospital than index presentation. CONCLUSION: A significant portion of
      patients (48.6%) who present to the ED with biliary colic will not return or have
      surgery within 5 years. A third of patients who eventually undergo
      cholecystectomy will go to another hospital for their surgery.

PMID- 29063308
TI  - Correction to: CASPer, an online pre-interview screen for personal/professional
      characteristics: prediction of national licensure scores.
AB  - In re-examining the paper "CASPer, an online pre-interview screen for
      personal/professional characteristics: prediction of national licensure scores"
      published in AHSE (22(2), 327-336), we recognized two errors of interpretation.

PMID- 29063307
TI  - Prospective evaluation of poly-4-hydroxybutyrate mesh in CDC class I/high-risk
      ventral and incisional hernia repair: 18-month follow-up.
AB  - BACKGROUND: Long-term resorbable mesh represents a promising technology for
      complex ventral and incisional hernia repair (VIHR). Preclinical studies indicate
      that poly-4-hydroxybutyrate (P4HB) resorbable mesh supports strength restoration
      of the abdominal wall. This study evaluated outcomes of high-risk subjects
      undergoing VIHR with P4HB mesh. METHODS: This was a prospective, multi
      institutional study of subjects undergoing retrorectus or onlay VIHR. Inclusion
      criteria were CDC Class I, defect 10-350 cm2, <= 3 prior repairs, and >= 1 high
      risk criteria (obesity (BMI: 30-40 kg/m2), active smoker, COPD, diabetes,
      immunosuppression, coronary artery disease, chronic corticosteroid use,
      hypoalbuminemia, advanced age, and renal insufficiency). Physical exam and/or
      quality of life surveys were performed at regular intervals through 18 months (to
      date) with longer-term, 36-month follow-up ongoing. RESULTS: One hundred and
      twenty-one subjects (46M, 75F) with an age of 54.7 +/- 12.0 years and BMI of 32.2
      +/- 4.5 kg/m2 (mean +/- SD), underwent VIHR. Comorbidities included the
      following: obesity (n = 95, 78.5%), hypertension (n = 72, 59.5%), cardiovascular
      disease (n = 42, 34.7%), diabetes (n = 40, 33.1%), COPD (n = 34, 28.1%),
      malignancy (n = 30, 24.8%), active smoker (n = 28, 23.1%), immunosuppression (n =
      10, 8.3%), chronic corticosteroid use (n = 6, 5.0%), advanced age (n = 6, 5.0%),
      hypoalbuminemia (n = 3, 2.5%), and renal insufficiency (n = 1, 0.8%). Hernia
      types included the following: primary ventral (n = 17, 14%), primary incisional
      (n = 54, 45%), recurrent ventral (n = 15, 12%), and recurrent incisional hernia
      (n = 35, 29%). Defect and mesh size were 115.7 +/- 80.6 and 580.9 +/- 216.1 cm2
      (mean +/- SD), respectively. Repair types included the following: retrorectus (n
      = 43, 36%), retrorectus with additional myofascial release (n = 45, 37%), onlay
      (n = 24, 20%), and onlay with additional myofascial release (n = 8, 7%). 95 (79%)
      subjects completed 18-month follow-up to date. Postoperative wound infection,
      seroma requiring intervention, and hernia recurrence occurred in 11 (9%), 7 (6%),
      and 11 (9%) subjects, respectively. CONCLUSIONS: High-risk VIHR with P4HB mesh
      demonstrated positive outcomes and low incidence of hernia recurrence at 18
      months. Longer-term 36-month follow-up is ongoing.

PMID- 29063310
TI  - Dose adjustment in obese breast cancer patients receiving neoadjuvant
      chemotherapy might have an impact on survival.

PMID- 29063309
TI  - Exercise following breast cancer: exploratory survival analyses of two
      randomised, controlled trials.
AB  - PURPOSE: The Exercise for Health trials were randomised, controlled trials
      designed to evaluate an 8-month pragmatic exercise intervention, commencing 6
      weeks post-surgery for women with newly diagnosed breast cancer residing in urban
      or rural/regional Australia. For these exploratory analyses, the primary and
      secondary outcomes were overall survival (OS) and disease-free survival (DFS),
      respectively. METHODS: Consenting urban- (n = 194) and rural/regional-residing
      women (n = 143) were randomised to exercise (intervention delivered face-to-face
      or by telephone) or usual care. Cox proportional hazards models were used to
      estimate hazard ratios (HRs) and 95% confidence intervals (CI) for survival
      outcomes (exercise group, n = 207, 65% urban women; usual care group, n = 130,
      46% urban women). RESULTS: After a median follow-up of 8.3 years, there were 11
      (5.3%) deaths in the exercise group compared with 15 (11.5%) deaths in the usual
      care group (OS HR for the exercise group: 0.45, 95% CI 0.20-0.96; p = 0.04). DFS
      events for the exercise versus usual care group were 25 (12.1%) and 23 (17.7%),
      respectively (HR: 0.66, 95% CI 0.38-1.17; p = 0.16). HRs for OS favoured exercise
      irrespective of age, body mass index, stage of disease, intervention compliance,
      and physical activity levels at 12 months post-diagnosis, although were stronger
      (p < 0.05) for younger women, women with stage II + disease, women with 1 +
      comorbidity at time of diagnosis, higher intervention compliance and for those
      who met national physical activity guidelines at 12 months post-diagnosis.
      CONCLUSION: An exercise intervention delivered during and beyond treatment for
      breast cancer, and that was designed to cater for all women irrespective of place
      of residence and access to health services, has clear potential to benefit
      survival. Trial numbers: ACT RN: 012606000233527; ACT RN: 12609000809235.

PMID- 29063311
TI  - Reclassifying HER2-equivocal disease.

PMID- 29063312
TI  - Canine invasive mammary carcinomas as models of human breast cancer. Part 2:
      immunophenotypes and prognostic significance.
AB  - PURPOSE: Relevant animal models of human breast cancer are currently needed,
      especially for the aggressive triple-negative breast cancer subtype. Recent
      studies and our results (Part 1) indicate that spontaneous canine invasive
      mammary carcinomas (CMCs) resemble human breast cancer by clinics and pathology
      as well as behavior and prognostic indicators. We hypothesized that the current
      molecular classifications of human breast cancer, used for therapeutic decision,
      could be relevant to dogs. METHODS: Three hundred and fifty female dogs with
      spontaneous CMC and a 2-year follow-up were retrospectively included. By
      immunohistochemistry, CMCs were classified according to Nielsen (Clin Cancer Res
      10:5367-5374, 2004) and Blows (PlosOne doi: 10.1371/journal.pmed.1000279, 2010)
      into the subtypes of human breast cancer. RESULTS: Four immunophenotypes were
      defined either according to Nielsen classification (luminal A 14.3%, luminal B
      9.4%, triple-negative basal-like 58.6%, and triple-negative nonbasal-like 17.7%
      CMCs); or to Blows classification (luminal 1-: 11.4%, luminal 1+: 12.3%, Core
      basal phenotype: 58.6%, and five-negative phenotype: 17.7%). No HER2
      overexpressing CMC as defined by a 3 + immunohistochemical score was observed in
      our cohort. By univariate and multivariate analyses, both immunophenotypical
      classifications applied to CMCs showed strong prognostic significance: luminal A
      or luminal 1+ CMCs showed a significantly longer disease-free interval (HR =
      0.46), Overall (HR = 0.47), and Specific Survival (HR = 0.56) compared to triple
      negative carcinomas, after adjustment for stage. CONCLUSIONS: In our cohort,
      triple-negative CMCs largely predominated (76%), were much more prevalent than in
      human beings, and showed an aggressive natural behavior after mastectomy. Dogs
      are thus potent valuable spontaneous models to test new therapeutic strategies
      for this particular subtype of breast cancer.

PMID- 29063314
TI  - Discrete Stretch Eliminates Electrophysiological Dose-Dependent Effects of Nitric
      Oxide Donor SNAP in Rat Atrium.
AB  - Depolarization of cardiomyocytes triggered by stretch and activation of
      mechanically gated ion channels can lead to serious arrhythmias. However, stretch
      induced signaling activating these channels remain little studied. This study
      tested the hypothesis on implication of NO in shaping the electrical
      abnormalities provoked by stretch of the right atrial myocardium in rat via a
      mechanism engaging a signaling cascade, where NO plays a significant role. This
      approach showed that in isolated right atrial preparation, NO donor SNAP induces
      the electrical abnormalities similar to those provoked by stretch, and the latter
      results from activation of NO synthase.

PMID- 29063313
TI  - Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic
      breast cancer: a phase 1b JAVELIN Solid Tumor study.
AB  - PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD
      L1) have shown antitumor activity in the treatment of metastatic breast cancer
      (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1
      inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid
      Tumor; NCT01772004), patients with MBC refractory to or progressing after
      standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks.
      Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were
      graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by
      immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168
      patients with MBC, including 58 patients with triple-negative breast cancer
      (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months.
      Patients were heavily pretreated with a median of three prior therapies for
      metastatic or locally advanced disease. Grade >= 3 treatment-related AEs occurred
      in 13.7% of patients, including two treatment-related deaths. The confirmed
      objective response rate (ORR) was 3.0% overall (one complete response and four
      partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR
      was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in
      the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs.
      2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical
      activity in a subset of patients with MBC. PD-L1 expression in tumor-associated
      immune cells may be associated with a higher probability of clinical response to
      avelumab in MBC.

PMID- 29063315
TI  - New Approach to Calculation of Renal Cation Clearance in Rats after V1a Receptor
      Stimulation.
AB  - V1a receptor agonist [Phe2, Ile3, Orn8]-vasopressin produces maximum diuretic and
      saluretic effects in a dose of 0.1 nmol/100 g body weight: renal excretion of Na+
      increases by 50 times in comparison with the initial level over 90 min, excretion
      of K+, Mg2+, and Sa2+ increases by 3, 2, and 16 times, respectively. New formulas
      were proposed for calculation of the clearance considering total cation content
      in the extracellular fluid and the time of total effect of the injected dose.
      After injection of V1a receptors agonist, clearance of Na+ was 7% of its total
      content in the extracellular fluid, the corresponding values for K+, Mg2+, and
      Ca2+ were 63, 35, and 6%, respectively. The proposed approach differs
      significantly from the standard cation excretion evaluation and characterizes
      selective shifts in ion balance induced by physiologically active substances and
      possible side effects due to unbalanced loss of certain ions.

PMID- 29063316
TI  - Modeling of Lymphogenous and Hematogenous Metastasizing from Murine V16 Melanoma
      in Rats.
AB  - We developed a model of experimental melanoma. Intralienal xenogeneic
      transplantation of a suspension of melanoma cells B16 in physiological saline
      (0.1 ml; 1:10) was conducted to outbred male rats. In 6 months, histologically
      confirmed melanoma B16 in the spleen and its metastases in the liver, intestine,
      pancreas, adrenal glands, and lungs (hematogenous metastasis), as well as in the
      thymus and lymph nodes (lymphogenous metastasis) were revealed in rats. The
      proposed rat model of melanoma B16 metastasizes by the hematogenous and
      lymphogenous pathways, develops over 6 months, and allows receiving sufficient
      volume of material for analysis.

PMID- 29063317
TI  - Effect of Phytoadaptogen Administration during Early Ontogeny on Lifespan and
      Somatic Status of CBA Mice with High Incidence of Tumors.
AB  - We studied the influence of nontoxic phytoadaptogen complex on the lifespan and
      somatic status (body weight, coat state, and motor activity) of CBA mice
      predisposed to spontaneous hepatomas. Administration of the complex
      phytoadaptogen during the first month of postnatal ontogeny increased mean animal
      lifespan by 17.1% (p<0.001) and median of survival by 25.6% (p<0.001) and
      promoted maintenance of satisfactory physical status of CBA mice during
      spontaneous hepatocarcinogenesis.

PMID- 29063318
TI  - Method of Selection of Bacteria Antibiotic Resistance Genes Based on Clustering
      of Similar Nucleotide Sequences.
AB  - A new method for selection of bacterium antibiotic resistance genes is proposed
      and tested for solving the problems related to selection of primers for PCR
      assay. The method implies clustering of similar nucleotide sequences and
      selection of group primers for all genes of each cluster. Clustering of
      resistance genes for six groups of antibiotics (aminoglycosides, beta-lactams,
      fluoroquinolones, glycopeptides, macrolides and lincosamides, and fusidic acid)
      was performed. The method was tested for 81 strains of bacteria of different
      genera isolated from patients (K. pneumoniae, Staphylococcus spp., S. agalactiae,
      E. faecalis, E. coli, and G. vaginalis). The results obtained by us are
      comparable to those in the selection of individual genes; this allows reducing
      the number of primers necessary for maximum coverage of the known antibiotic
      resistance genes during PCR analysis.

PMID- 29063319
TI  - Pattern of Notch2, Numb, and Cas8 Gene Expression in Relevant Structures of the
      Rat Brain during Formation of Spatial Memory.
AB  - The expression of Notch2, Numb, and Cas8 genes, whose protein products are
      involved in regulation of neurogenesis/neuroapoptosis processes, was studied in
      the relevant cerebral structures of male Wistar rats trained in a spatial habit.
      The formation of long-term spatial memory was found to be associated with the
      formation of a specific pattern of transcription activity of the studied genes in
      different brain structures. The maximum expression of Notch2 gene was found in
      the hippocampus and cerebellum, the maximum expression of Numb was detected in
      the prefrontal cortex and cerebellum, and the maximum expression of Cas8 was
      revealed in the prefrontal cortex of trained animals.

PMID- 29063320
TI  - Study of Sedative Tea Phytocomplex within the Framework of Studies Aimed at
      Creation of a Rectal Dosage Form with Antihistaminic Effect.
AB  - We designed a new complex drug with antiallergic effect containing, in addition
      to the main component loratadine, a phytocomplex for an extra therapeutic effect.
      A collection of plants with sedative activity is chosen and the optimal agent for
      extraction of bioactive compounds (40% ethanol) and optimal degree of plant
      fragmentation are determined. Chemical composition of the sedative tea is
      evaluated by reverse phase HPLC. The marker components of the species are
      detected: xanthohumol and isoxanthohumol - Humulus lupulus cone components,
      Mentha piperita rosmarinic acid, and scutellareine, Menyanthes trifolia element -
      quercetin-3-rutinoside, and caffeic acid. Standardization of the species by the
      absolute graduation method in conversion to quercetin-3-rutinoside is suggested.

PMID- 29063321
TI  - Elimination of a Viscumin-Ferromagnetic Nanoparticles Conjugate from the Tumor
      Nodule in Mice.
AB  - External magnetic field is characterized by low toxicity and existence of
      magnetic properties, which contributes to an interest in the development of
      products from ferromagnetic nanoparticles (FNP) for antitumor therapy. Previously
      we synthesized a conjugate of ferromagnetic magnetite nanoparticles and viscumin
      (mistletoe lectin I, MLI), which exhibits the antitumor activity. Studying the
      pharmacological properties of this conjugate (FNP-MLI) was directed to the
      evaluation of FNP-MLI elimination after intratumor injection in mice. The
      elimination rate of FNP-MLI was much lower than that of native plant MLI. The
      presence of FNP-MLI was not accompanied by undesired changes in the tumor tissue.
      The use of a FNP-MLI conjugate allowed us to prolong the time of MLI presence in
      tissues without increasing the dose of exogenous lectin. These features
      contribute to the prolongation of an immunomodulatory effect of MLI.

PMID- 29063323
TI  - Ultrastructural Morphological Characterization of Right Atrial and Left
      Ventricular Rat Cardiomyocytes during Postreperfusion Period.
AB  - Immunocytochemistry and transmission electron microscopy were employed to examine
      the ultrastructural morphometric parameters of the left ventricular
      cardiomyocytes and right atrial secretory myocytes in rats during early and
      delayed postreperfusion periods. The revealed alterations in these cells are
      stereotypical, but differed by their severity, probably due to specific
      morphofunctional peculiarities of these heart structures.

PMID- 29063322
TI  - Analysis of Immunogenicity of Intracellular CTAR Fragments of Epstein-Barr Virus
      Latent Phase Protein LMP1.
AB  - Intracellular fragments of latent phase protein LMP1 of Epstein-Barr virus,
      denoted as CTAR1/2/3, can trigger a variety of cell cascades and contribute to
      the transforming potential of the virus. Generation of recombinant proteins
      CTAR1/2/3 is expected to yield more ample data on functional and immunogenic
      characteristics of LMP1. We created genetic constructs for prokaryotic expression
      of LMP1 CTAR fragments and selected optimal conditions for their production and
      purification. Using a new library of LMP1 CTAR fragments, we carried out epitope
      mapping of a diagnostic anti-LMP1 antibody S12. Analysis of polyclonal serum
      antibodies from mice immunized with full-length LMP1 confirmed immunogenicity of
      CTAR elements comparable with that of full-length protein.

PMID- 29063324
TI  - Expression of Flk-1 and Cyclin D2 mRNA in the Myocardium of Rats with Doxorubicin
      Induced Cardiomyopathy and after Treatment with Betulonic Acid Amide.
AB  - The expression of VEGFR2 (Flk-1, according to immunohistochemistry) and of cyclin
      D2 mRNA (according to real-time PCR) in the myocardium of rats is studied in
      doxorubicin-induced cardiomyopathy and in response to betulonic acid amide.
      Doxorubicin alone and in combination with betulonic acid amide causes after 3
      days a manifest reduction of cyclin D2 mRNA expression (by 38 and 63%,
      respectively), while injection of betulonic acid amide alone causes a 23-fold
      increase of cyclin D2 mRNA expression. An increase of cyclin D2 mRNA expression
      has been detected in all experimental groups after 14 days of experiment, the
      most pronounced in response to betulonic acid amide (63 times). The expression of
      Flk-1 in cardiomyocytes increases significantly in response to both chemical
      agents starting from day 3 of experiment. These results indicate that doxorubicin
      and betulonic acid amide induce cytoprotective reactions in the myocardium, first
      at the intracellular, then at the cellular levels.

PMID- 29063325
TI  - Comparative Study of Sutureless Fixation of Lightweight Surgical Meshes for
      Hernia Repair in a Rat Model.
AB  - The aim of this study was to compare the efficacy of different methods of
      sutureless fixation of lightweight meshes made of different polymers for repair
      of experimental hernias. Two lateral hernia defects were modeled in male rats and
      covered with polyester and polypropylene prostheses. The meshes were fixed with
      Histacryl glue (group 1), or self-gripping meshes were used (group 2), or the
      meshes were implanted without fixation (group 3). On day 5 after surgery, mesh
      position and efficiency of fixation were evaluated. It was found that fixation is
      necessary for all light surgical meshes. Polyester meshes demonstrated better
      adhesive properties than polypropylene meshes. The most pronounced differences in
      the adhesive properties were found for self-gripping prosthesis, while in the
      groups with glue fixation, the differences were less pronounced.

PMID- 29063326
TI  - Comparative Effects of Platelet-Rich Plasma, Platelet Lysate, and Fetal Calf
      Serum on Mesenchymal Stem Cells.
AB  - We studied the effects of human platelet-rich plasma and platelet lysate on
      proliferation, migration, and colony-forming properties of rat mesenchymal stem
      cells. Platelet-rich plasma and platelet lysate stimulated the proliferation,
      migration, and colony formation of mesenchymal stem cells. A real-time study
      showed that platelet-rich plasma produces the most potent stimulatory effect,
      while both platelet-rich plasma and platelet lysate stimulated migration of
      cells.

PMID- 29063327
TI  - Design of Nanosomal Form of Aprotinin.
AB  - Liposomes containing aprotinin were produced by the phase inversion technique and
      purified by gel filtration. Aprotinin inclusion was assessed fluorescence
      labeling of the protein. The size of obtained liposomes was 212+/-35 nm and
      aprotinin concentration in the liposomal suspension was 3000 KIU/ml. The
      efficiency of aprotinin inclusion into liposomes was 31.9%.

PMID- 29063328
TI  - Correlation between LC50 for Adult Fish and Fish Embryos.
AB  - Testing for substance toxicity for living organisms is an important step in the
      development and adaptation of new drugs for various purposes. Analysis of the
      dependences between toxicological parameters of chemical substances for various
      test objects and physicochemical properties of these agents is a promising trend.
      Partition coefficient logP (logKow) was chosen as the key physicochemical
      parameter determining the toxicological parameters of the same substance for
      hydrobionts at different developmental stages. We found a correlation between
      decimal logarithm of the ratio of LCe50 for fish embryos to LCa50 for adult fish
      and logP. This dependence was found as a liner combination of equations obtained
      by drawing a trend line between experimental points and calculation of Pearson's
      correlation coefficient R.

PMID- 29063329
TI  - Analysis of the Efficiency of Microencapsulated Sustained-Release Form of
      Naloxone on the Experimental Model of Fentanyl Poisoning.
AB  - We compared samples of microencapsulated naloxone prepared by using spray drying
      technique. 2-Hydroxypropyl-beta-cyclodextrin, sodium alginate, polycaprolactone,
      and carboxymethyl cellulose were used as the carriers. It was found that the
      combination of naloxone with sodium alginate was characterized by the highest
      naloxone content in the matrix and the lowest release rate (100% release time was
      60 min). Using the model of respiratory disturbances caused by 10 ED50 fentanyl
      (anesthetic effect), we studied the effects of naloxone-sodium alginate complex
      on the dynamics of CO2 concentration in the expired air. It was shown that
      treatment with the developed microencapsulated naloxone after fentanyl injection
      allowed reducing the therapeutic dose of the antagonist by more than 2 times and
      eliminated the necessity of repeated injections.

PMID- 29063330
TI  - Effects of Oxytocin on the Levels and Metabolism of Monoamines in the Brain of
      White Outbred Mice during Long-Term Social Isolation.
AB  - The effects of intranasal administration of oxytocin on the levels and metabolism
      of monoamines in symmetrical structures of the brain of white outbred mice kept
      under conditions of long-term social isolation were studied by HPLC.
      Disappearance of initial right-sided asymmetry in the content of dopamine
      metabolites in the striatum, increased 5-hydroxyacetic acid content in the right
      striatum, and disappearance of the initial left-sided asymmetry in serotonin
      level in the cortex were noted; we also found a decrease in norepinephrine
      content in the left hippocampus with appearance of asymmetry and higher content
      in the right olfactory tubercle. It can be hypothesized that minor changes in the
      serotoninergic and dopaminergic systems against the background of high reactivity
      of noradrenergic system represent specific response of the brain to oxytocin in
      aggressive animals.

PMID- 29063331
TI  - Role of LIF Cytokine and CD34 Angiogenesis Marker in Non-Developing Pregnancy.
AB  - The expression of cytokine LIF (leukemia inhibiting factor) in the endometrium of
      women of young reproductive age with non-developing pregnancy of unknown genesis
      is higher than in older women and women with infection-related miscarriages by
      1.26 and 1.43 times, respectively. The expression of angiogenesis marker CD34 in
      the endometrium of young women with non-developing pregnancy of unknown origin is
      1.59 times higher and in case of endometrial inflammation 1.31 times higher than
      in women of the older reproductive age with the same disease. Correlation between
      the endometrial expression of LIF and CD34 is detected in women of the younger
      reproductive age with non-developing pregnancy of unknown etiology. The
      expression of LIF and CD34 can be used for endometrial function evaluation in
      women of different age with first trimester non-developing pregnancy.

PMID- 29063332
TI  - Pretreatment with Antiviral Preparation Kagocel Normalizes the Content of Bone
      Marrow Multipotent Stromal Cells and TNFalpha in Blood Serum of CBA Mice
      Disturbed by Administration of S. typhimurium Antigen Complex In Vivo and
      Maintains High Concentration of IL-10 and Th1 Cytokines.
AB  - Pretreatment with the active substance of antiviral preparation Kagocel, inductor
      of type I endogenous IFN, in a daily therapeutic dose (30 MUg/mouse) 3 h prior to
      administration of S. typhimurium antigens to CBA mice reduced the number of bone
      marrow multipotent stromal cell (significantly increased by 3.2 times on the next
      day after antigen injection) to the initial level. Thus, activation of the
      stromal tissue induced by administration of the bacterial antigen was blocked. In
      addition, preliminary administration of Kagocel modulated the cytokine profile of
      the blood serum affected by S. typhimurium antigens: reduced 1.6-fold elevated
      concentration a proinflammatory cytokine TNFalpha to the control level (in 4 h
      after antigen injection) and maintained this level in 20 h after antigen
      administration. Kagocel also maintained the concentration of anti-inflammatory
      cytokine IL-10 at the level surpassing the normal by 1.6 times and high
      concentrations of Th1 cytokines (IL-2, IFNgamma, and IL-12). These results
      suggest that Kagocel can reduce the immune response to bacterial antigens
      (similar to type I IFN [7]), which can contribute to its therapeutic and
      preventive effects in addition to its well documented antiviral activity and then
      this preparation can be used for the therapy of diseases accompanied by excessive
      or chronic inflammation.

PMID- 29063333
TI  - Studying the Toxic Effects of Some Biologically Active Peptides on the Model of
      Mouse Embryonic Stem Cells.
AB  - We studied the effects of peptide drugs (HLDF-6, PGP, RPGP, and PGLP) and peptide
      pharmaceutical products (Semax, Selank, and thyroliberin) on proliferation and
      survival of mouse embryonic stem cells and their derivatives. Differentiation of
      mouse embryonic stem cells into neuronal precursors was evaluated. PGP and PGLP
      in concentrations of 10 and 0.1 MUM, respectively, had little, but significant
      inhibitory effect on proliferative activity of cells. These peptides in
      concentrations of 10 and 0.1 MUM, respectively, and Semax (10 and 0.1 MUM)
      significantly increased the survival rate of mouse embryonic stem cells (serum
      deprivation). Moreover, study peptides had little effect on the formation of
      neuronal precursors from mouse embryonic stem cells. HLDF-6, Selank, and
      thyroliberin produced an insignificant effect on the differentiation of these
      cells into mature neurons. Analysis of differentiation of embryonic stem cells
      into GABA+ neurons showed that Selank, thyroliberin (100 MUM), and NGF (100
      ng/ml) decrease the ratio of these cells by 61, 58, and 87%, respectively, in
      comparison with the control. Our results indicate that these peptide compounds do
      not produce toxic effect during the embryonic and fetal period of life.

PMID- 29063334
TI  - Effects of Multicide, Antibacterial Drug, on Staphylococcus Biomembranes.
AB  - Drug penetration into bacterial biomembranes is one of the most important factors
      determining the efficiency of antibacterial therapy. Multicide, antibacterial
      drug, is a nanomolecule 1.3-2.0 nm in size, easily penetrating into
      staphylococcus biomembranes and causing rapid death of bacteria. The drug
      efficiency depends on its concentration and duration of exposure. Bacteria die as
      a result of cell wall perforation, which is associated with changes in its
      morphology and release of DNA from bacterial cell into the environment. Our
      results indicate the efficiency of primary damage to bacterial wall leading to
      elimination of biomembranes.

PMID- 29063335
TI  - Selectivity in Physiological Action of Nitric Oxide: A Hypothetical Mechanism.
AB  - The study showed that dinitrosyl iron complex (NO)2Fe(RS)2 containing the
      thiolate ligands, which is the basic physiological donor of NO, can transfer NO
      to other molecule only at the moment of rearrangement. This rearrangement can
      occur during interaction of the complex with more effective iron chelators than
      the thiolate ligands. In the absence of NO trap, a new complex is formed with a
      new ligand. NO transfer to a trap can also occur under the action of the agents
      such as mercury salts or ROS, which interact with the thiolate ligands. Probably,
      the ligands in the dinitrosyl iron complexes are the structures responsible for
      interaction of these complexes with physiological targets and for specificity and
      effectiveness of this interaction.

PMID- 29063336
TI  - Role of beta2-Adrenoreceptors in Adrenergic Anti-Inflammatory Mechanism in
      Sepsis.
AB  - Experiments on random-bred albino mice showed that of beta2-adrenoreceptor
      agonist hexaprenaline sulfate significantly reduced mortality of mice from
      experimental sepsis (intraperitoneal administration of E. coli) in 4 and 24 h
      after modeling by reducing blood levels of proinflammatory cytokines TNFalpha, IL
      1beta, and IL-6. The antagonist of beta2AR ICI-118,551 eliminated this effect.

PMID- 29063338
TI  - Effect of Lipid Surface Composition on the Formation and Structure of Fibrin
      Clots.
AB  - We studied the influence of lipid surface composition on the kinetics of fibrin
      clot formation and its structure. It was shown that lipid surface affects all
      phases of fibrin polymerization and chances clot morphology. The magnitude and
      character of the effect depend on the charge and phase state of lipids that
      determine the interaction of fibrinogen with the lipid surface and its
      conformational changes, which modulated the process of fibrinogen conversion into
      fibrin and, as a result, the formation and morphology of the fibrin clot.

PMID- 29063337
TI  - Mast Cells in Renal Cancer: Clinical Morphological Correlations and Prognosis.
AB  - Morphofunctional activity of mast cells in renal cancer is studied on specimens
      from the center of the tumor, peritumorous zone (with an obligatory fragment of
      the pseudocapsule), and from renal tissues maximally distant from the tumor. The
      counts and areas of tumor cells were maximum in the peritumorous zone in
      comparison with intact kidney tissue and central zone of the tumor. Analysis of
      correlations revealed a direct correlation between the tumor cell count in the
      peritumorous zone and some clinical morphological parameters of the tumor
      (anaplasia degree, size, presence of invasion and metastases, and angiogenesis).
      The count of mast cells in the renal peritumorous zone inversely correlated with
      5-year survival: 100% cumulative 5-year survival in patients with mast cell count
      <6.7+/-1.6 per field of view.

PMID- 29063339
TI  - Metagenomic Analysis of Gingival Sulcus Microbiota and Pathogenesis of
      Periodontitis Associated with Type 2 Diabetes Mellitus.
AB  - Biofilm of the gingival sulcus from 22 patients with type 2 diabetes mellitus and
      periodontitis, 30 patients with periodontitis not complicated by diabetes
      mellitus (reference group), and 22 healthy volunteers without signs of gingival
      disease (control group) was studied by quantitative PCR. Quantitative analysis
      for the content of P. gingivalis, T. forsythia, A. ctinomycetemcomitans, T.
      denticola, P. intermedia, F. nucleatum/periodonticum, and P. endodontalis in the
      dental plaque was performed with a Dentoscreen kit. The presence of other
      bacterial groups was verified by metagenomic sequencing of the 16S rRNA gene to
      evaluate some specific features of the etiological factor for periodontitis in
      type 2 diabetes mellitus. Specimens of the Porphiromonadaceae and
      Fusobacteriaceae families were characterized by an extremely high incidence in
      combined pathology. The amount of Sphingobacteriaceae bacteria in the biofilm was
      shown to decrease significantly during periodontitis. Metagenomic analysis
      confirmed the pathogenic role of microbiota in combined pathology, as well as the
      hypothesis on a possible influence of periodontitis on the course and development
      of type 2 diabetes mellitus.

PMID- 29063340
TI  - Antibacterial Activity of L-Lysine-alpha-Oxidase from the Trichoderma.
AB  - We studied the effects of a concentrate of metabolites of Trichoderma harzianum
      Rifai F-180, an active producer of L-lysine-alpha-oxidase, and homogenous enzyme
      on a highly virulent bacteria Erwinia amylovora. The producer of antitumor and
      antiviral Trichoderma enzyme L-lysine-alpha-oxidase was cultured on a processing
      system of G. K. Skryabin Institute of Biochemistry and Physiology of
      Microorganisms, Russian Academy of Sciences (Pushchino). Activity of L-lysine
      alpha-oxidase in the prepared concentrate of metabolic products of the producer
      was 5.4 U/ml, and activity of the homogenous enzyme was 50 U/ml. Antibacterial
      activity of the enzyme was shown in our experiments.

PMID- 29063341
TI  - Involvement of Microflora Metabolites in Up-Regulation of Electrical Activity in
      Rat Small Intestine.
AB  - The study examined implication of tributyrin, a metabolic precursor in small
      intestinal microflora, in stimulation of electrical activity of duodenum and
      jejunum. Enteral administration of tributyrin enhanced electrical activity of
      both examined structures in small intestine with elimination of the rest periods.
      The stimulatory effect was manifested in a prolongation of the periods of
      irregular activity. The up-regulating effects of tributyrin on electrical
      activity in upper segments of small intestine are mediated via the
      cholecystokinin receptors being also associated with activation of cholinergic
      and blockade of nitrinergic signal transduction pathways.

PMID- 29063342
TI  - Microradiopharmaceutical for Metastatic Melanoma.
AB  - PURPOSE: The purpose of this article was to develop, characterize and test (in
      vivo) dacarbazine microparticles that may be labeled with 99mTc and Ra-223 for
      both use: diagnostic and therapy of metastatic melanoma. METHODS: We developed by
      double emulsion solvent evaporation methodology the microparticle. The
      characterization has been done using, Dynamic Light Scattering (DLS) and Scanning
      Electron Microscopy (SEM). The labeling with 99mTc and Ra-223 has been done by
      the direct labeling process. Also the formulation has been tested pre-clinically
      using Balb/c mice inducted with melanoma, performing the the biodistribution and
      planar imaging. Cytotoxicity evaluation was also done in M3 V cell line. In order
      to understand the safety aspects of the microparticles, microbiological study
      (endotoxin and sterility) has been done. Finally, planar imaging was performed to
      evaluate the diagnosing aspect. RESULTS: The results showed that a 559 nm
      microparticles was obtained with a spherical shape. The labeling process with
      99mTc reached over 90% of efficacy. On the other hand, the labeling process with
      Ra-223 showed a 70% efficacy. The results in inducted animals demonstrated that
      the microparticles were able to reach the tumor with a high rate (20%). Also
      demonstrated a low recognition by the Mononuclear Phagocytic System. The
      cytotoxicity and the microbiological control, corroborates the safety aspect of
      these microparticles. CONCLUSION: The planar image and the possible labeling with
      Ra-223, corroborates the use as a theragnostic agent for imaging and therapy of
      Metastatic Melanoma.

PMID- 29063343
TI  - Acetaminophen clearance during ex vivo continuous renal replacement therapies.
AB  - Intravenous acetaminophen is an adjuvant to opioid use in critically ill and
      surgical patients requiring continuous renal replacement therapy (CRRT). The
      objective of this study was to determine the ex vivo transmembrane clearance of
      intravenous acetaminophen during continuous hemofiltration and hemodialysis.
      Transmembrane clearance was assessed using a validated ex vivo bovine blood model
      for CRRT using an F8 or HF1400 hemodiafilter. Ultrafiltrate and dialysate flow
      rates were 1, 2, and 3 L/h. Urea and acetaminophen clearances were calculated and
      compared. Acetaminophen was readily cleared by continuous hemofiltration with
      both hemodiafilters. Acetaminophen clearance rates were 92-98% of ultrafiltrate
      production rates. Similarly, dialytic acetaminophen clearances approximated
      dialysate flow rates for both hemodiafilters. Acetaminophen is readily cleared by
      CRRT. Patients receiving CRRT and acetaminophen may require increased doses for
      adequate pain control.

PMID- 29063344
TI  - Haematospirillum and insect Wolbachia DNA in avian blood.
AB  - In this study, blood samples of 259 Acrocephalus sp. warblers were molecularly
      analysed for Anaplasmataceae and Rhodospirillaceae based on PCR amplification of
      16S rRNA gene fragments. One bird blood sample (from Reed Warbler, Acrocephalus
      scirpaceus) yielded a sequence with 99.8% identity to Haematospirillum jordaniae.
      This is the first molecular evidence for the occurrence of this species in the
      blood of any vertebrate other than human. Another bird blood sample (from Marsh
      Warbler: Acrocephalus palustris) yielded a Wolbachia sequence, closely related to
      a moth endosymbiont with 99.8% identity. A nematode origin of Wolbachia DNA
      detected here in avian blood can be excluded, because results of phylogenetic
      analysis showed its closest alignment with insect wolbachiae. This is the first
      finding of insect Wolbachia DNA in the circulatory system of birds, which can be
      explained either by the inoculation of wolbachiae by blood-sucking vectors, or
      passing of Wolbachia DNA from the gut into the blood of this insectivorous bird
      species.

PMID- 29063346
TI  - Tho' Much is Taken, Much Abides: Asylum Seekers' Subjective Wellbeing.
AB  - The influence of psychosocial factors on the subjective wellbeing of asylum
      seekers residing in host Western countries has scarcely been explored
      qualitatively. Qualitative data derived from a mixed methods prospective study
      investigated the subjective wellbeing of 56 community-dwelling asylum-seekers and
      refugees at baseline and an average of 15.7 months later. Positive and negative
      experiences over time were explored in relation to self-perceived emotional
      health. Nineteen positive and 15 negative categories of experience emerged.
      Distinct psychosocial and protective factors were salient regarding the valence
      of experiences over time, with positive experiences comprising employment,
      improved financial circumstances, and social support or connectivity. Negative
      experiences included news of adversity from one's homeland, un(der)employment,
      poor health, and factors relating to the refugee determination process. Positive
      and negative experiences were contemporaneous, indicating that employment and
      social support may ameliorate the detrimental impact of traversing the protracted
      process of refugee status determination for asylum-seekers in particular.

PMID- 29063345
TI  - Cessation of annual apical growth and partial death of cambium in stem of Abies
      sachalinensis under intensive shading.
AB  - This study evaluated variation in the height at which absent rings and internodes
      were detected along stem of Abies sachalinensis trees grown under shade for 39
      years. Eight sample trees planted in 1974 under a secondary forest in Japan were
      felled in 2013 and analyzed. A. sachalinensis is a monopodial species in which it
      is possible to measure annual apical growth using the distinct internodes. We
      applied microscopic analysis on 154 stem disks from the stem base to the top to
      evaluate the cessation of apical and radial growth caused by intensive shading.
      Cessation of apical stem growth for one or more years was found in 6 out of 8
      sample trees. We termed this phenomenon as "absent internode". In addition, the
      absent growth rings were detected more frequently in the lower part of sample
      stems, and the number of absent rings at the stem base did not correspond with
      the number of absent internodes in the six trees. From cellular level
      observation, the five suppressed trees had no living cambial cells at the stem
      base but had living cells at the stem top. The cessation of the apical and radial
      growth did not occur synchronously but did occur independently under a shade
      environment in A. sachalinensis.

PMID- 29063347
TI  - Nrf2 Signaling Pathway Mediates the Antioxidative Effects of Taurine Against
      Corticosterone-Induced Cell Death in HUMAN SK-N-SH Cells.
AB  - Substantial evidence has shown that elevated circulating corticosteroids or
      chronic stress contributes to neuronal cell death, cognitive and mental
      disorders. However, the underlying mechanism is still unclear. Taurine is
      considered to protect neuronal cells from apoptotic cell death in
      neurodegenerative diseases and neuropsychiatric disorders. In the present study,
      the protective effects of taurine against corticosterone (CORT)-induced oxidative
      damage in SK-N-SH neuronal cells were investigated. The results showed that CORT
      significantly induced cell death, which was blocked by pretreatment with taurine.
      Similarly, pretreatment with taurine suppressed CORT-induced apoptotic cell death
      decreasing the levels of intracellular reactive oxygen species and improving
      mitochondrial function. Pretreatment with taurine increased the expression of
      phosphorylated extracellular regulated protein kinases (ERK) as well as the
      nuclear translocation of nuclear factor (erythroid 2-derived)-like 2 (Nrf2) in
      the CORT rich environment. Furthermore, administration of the ERK inhibitor U0126
      or transient (siRNA) silencing of Nrf2 blocked the protective effects of taurine
      on cell viability and expression levels of Nrf2 and heme oxygenase-1 (HO-1) in
      the CORT model of neuronal damage. These results suggest that the Nrf2 signaling
      pathway may play a role in the protection mechanism of taurine against CORT
      induced neuronal oxidative damage.

PMID- 29063349
TI  - Electroconvulsive therapy does not alter the synaptic protein neurogranin in the
      cerebrospinal fluid of patients with major depression.
AB  - Neurogranin (Ng) is a dendritic protein associated with synaptic plasticity,
      proposed to be a novel biomarker to measure synaptic dysfunction and degeneration
      in Alzheimer's disease. Since electroconvulsive therapy (ECT) has been suggested
      to facilitate neurogenesis and neural plasticity, we tested whether ECT could
      modify CSF Ng concentrations measured before and after a course of ECT in 12
      patients with major depression. CSF Ng concentrations did not change, but
      baseline levels were positively correlated with the therapeutic response.

PMID- 29063350
TI  - Bias in retrospective assessment of perceived dental treatment effects when using
      the Oral Health Impact Profile.
AB  - PURPOSE: Aim of this exploratory study was to investigate whether a retrospective
      assessment of oral health-related quality of life (OHRQoL) using the Oral Health
      Impact Profile (OHIP) is susceptible to bias such as implicit theory of change
      and cognitive dissonance. METHODS: In this prospective clinical study, a sample
      of 126 adult patients (age 17-83 years, 49% women) requiring prosthodontic
      treatment was consecutively recruited. The OHRQoL was assessed using the 49-item
      OHIP at baseline and at follow-up. Additionally, patients were asked at follow-up
      to retrospectively rate their oral health status at baseline (retrospective
      pretest or then-test) and the change in oral health status using a global
      transition question. Furthermore, patients' ratings of overall oral health and
      general health were used as validity criteria for the OHRQoL assessments.
      Response shift was calculated as the difference between the initial and
      retrospective baseline assessments. RESULTS: Baseline and retrospective pretest
      did not differ substantially in terms of internal consistency and convergent
      validity. Response shift was more pronounced when patients perceived a large
      change in OHRQoL during treatment. Retrospective pretests were more highly
      correlated with the baseline than with the follow-up assessment. CONCLUSION:
      Findings suggest that retrospective assessments of OHRQoL using the OHIP-49 are
      susceptible to bias. Cognitive dissonance is more likely to appear as a source of
      bias than implicit theory of change.

PMID- 29063348
TI  - Differential contribution of microglia and monocytes in neurodegenerative
      diseases.
AB  - Neuroinflammation is a hallmark of neurodegenerative diseases including
      Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral
      sclerosis (ALS). Microglia, the innate immune cells of the CNS, are the first to
      react to pathological insults. However, multiple studies have also demonstrated
      an involvement of peripheral monocytes in several neurodegenerative diseases. Due
      to the different origins of these two cell types, it is important to distinguish
      their role and function in the development and progression of these diseases. In
      this review, we will summarize and discuss the current knowledge of the
      differential contributions of microglia and monocytes in the common
      neurodegenerative diseases AD, PD, and ALS, as well as multiple sclerosis, which
      is now regarded as a combination of inflammatory processes and neurodegeneration.
      Until recently, it has been challenging to differentiate microglia from
      monocytes, as there were no specific markers. Therefore, the recent
      identification of specific molecular signatures of both cell types will help to
      advance our understanding of their differential contribution in neurodegenerative
      diseases.

PMID- 29063351
TI  - Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with
      Discordant Handedness.
AB  - Handedness differentiates patterns of neural asymmetry and interhemispheric
      connectivity in cortical systems that underpin manual and language functions.
      Contemporary models of cerebellar function incorporate complex motor behaviour
      and higher-order cognition, expanding upon earlier, traditional associations
      between the cerebellum and motor control. Structural MRI defined cerebellar
      volume asymmetries and correlations with corpus callosum (CC) size were compared
      in 19 pairs of adult female monozygotic twins strongly discordant for handedness
      (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated
      parcellation.CC area and regional widths were obtained from midsagittal
      planimetric measurements. Within the cerebellum and CC, neurofunctional
      distinctions were drawn between motor and higher-order cognitive systems.
      Relationships amongst regional cerebellar asymmetry and cortical connectivity (as
      indicated by CC widths) were investigated. Interactions between hemisphere and
      handedness in the anterior cerebellum were due to a larger right-greater-than
      left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH)
      twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor
      control were associated with CC size, particularly in callosal regions associated
      with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI,
      Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness
      group. These novel results reflected distinct patterns of cerebellar-cortical
      relationships delineated by specific CC regions and an anterior-posterior
      cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may
      contribute to the greater degree of bilateral cortical organisation of frontal
      motor function in LH individuals.

PMID- 29063352
TI  - Multivariable Analysis of Gluten-Free Pasta Elaborated with Non-Conventional
      Flours Based on the Phenolic Profile, Antioxidant Capacity and Color.
AB  - The phenolic compounds, color and antioxidant capacity of gluten-free pasta
      prepared with non-conventional flours such as chickpea (CHF), unripe plantain
      (UPF), white maize (WMF) and blue maize (BMF) were analyzed. Fifteen phenolic
      compounds (five anthocyanins, five hydroxybenzoic acids, three hydroxycinnamic
      acids, one hydroxyphenylacetic acid and one flavonol) were identified in pasta
      prepared with blue maize, and 10 compounds were identified for samples prepared
      with white maize. The principal component analysis (PCA) led to results
      describing 98% of the total variance establishing a clear separation for each
      pasta. Both the proportion (25, 50 and 75%) and type of maize flour (white and
      blue) affected the color parameters (L*, C ab *, h ab and DeltaE* ab ) and
      antioxidant properties (DPPH, ABTS and FRAP methods) of samples, thus producing
      gluten-free products with potential health benefits intended for general
      consumers (including the population with celiac disease).

PMID- 29063353
TI  - High prevalence and antimicrobial resistance of mecA Staphylococcus aureus in
      dairy cattle, sheep, and goat bulk tank milk in Jordan.
AB  - The aim of this study was to determine the prevalence and antimicrobial
      resistance of mecA and mecC methicillin-resistant Staphylococcus aureus (MRSA) in
      cattle, sheep, and goat dairy farms in Jordan. Milk samples were collected from
      bulk tanks at 117 dairy farms (44 cattle, 47 sheep, and 26 goat dairy farms) in
      each region of the country. MRSA were isolated on mecA and mecC chromogenic media
      and confirmed by PCR. The confirmed isolates were tested for resistance toward 15
      antimicrobials by the disc diffusion method. None of the tested bulk milk samples
      were positive for mecC and 26% (95% CI 20-32%) were positive for mecA MRSA.
      Specifically, mecA MRSA was detected in 31.8% (95% CI 17.5-46.1) of cattle, 29.8%
      (95% CI 16.2-43.4) of sheep, and 11.5% (95% CI - 1.6-24.7%) of goat dairy farms.
      All isolates (n = 86) exhibited resistance to penicillin, oxacillin, cefoxitin;
      meanwhile, most isolates (70-85%) exhibited resistance toward gentamicin,
      clindamycin, rifampicin, neomycin, fusidic acid, erythromycin, tetracycline, and
      ciprofloxacin. All mecA MRSA isolates were resistant to at least one class of
      antimicrobials. Isolates from all goat milk, 88% of cattle milk, and 87% of sheep
      milk samples exhibited resistance to three classes of antimicrobials and were
      considered multidrug resistant (MDR). These data demonstrate widespread MDR MRSA
      in dairy ruminants in Jordan, and these rates are higher than those reported in
      other countries. Such high prevalence of MDR MRSA and mecA MRSA could lead to
      economic losses in the dairy industry in Jordan and poses a possible public
      health risk.

PMID- 29063354
TI  - Effects of substituting sow and weaner meal with brewers' spent grains on the
      performance of growing pigs in Rwanda.
AB  - Nutrient composition of brewers' spent grains (BSG) from two industries and sow
      and weaner meal (SWM) were different (p < 0.05). In completely randomised design
      (CRD), thirty (30) Landrace x Pietrain crosses 35 to 40 +/- 5 kg were randomly
      allocated to 10 pens each with 3 pigs based on the initial weight. Five diets
      were assigned to pig, where BSG replaced SWM at 0% (T1), 25% (T2), 50% (T3), 75%
      (T4) and 100% (T5) on DM basis. Daily feed intake and weekly live weight, feed
      conversion ratio (FCR) and the net profit were recorded for 42 days. Feed intake
      increased from T1-T3 and then decreased (p < 0.05). The average daily gains (ADG)
      were different (p < 0.05), but T1 to T3 were similar (p > 0.05). FCR was similar
      (p > 0.05) from T1 to T3 but different for T4 and T5 (p < 0.05). Feed cost
      decreased with the increase in BSG levels. The net return was highest in T3 (50%
      BSG) than in T1 and T2 but lower in T5. It was concluded that BSG can replace 50%
      SWM in grower pigs' diets without adverse effect on daily gain with good economic
      returns.

PMID- 29063355
TI  - Comment on "Serum human epididymis protein 4 is associated with the treatment
      response of concurrent chemo-radiotherapy and prognosis in patients with locally
      advanced non-small cell lung cancer" by Lan WG et al.

PMID- 29063356
TI  - Changing trends in postoperative cataract care: impact of electronic patient
      records in optometrist-delivered shared care.
AB  - BACKGROUND: This study evaluates a community optometrist-delivered postoperative
      care scheme in patients discharged from the hospital ophthalmology department
      following uncomplicated cataract surgery. AIM: The aim of this study is to assess
      the efficacy of electronic patient records (EPR) in facilitating co-managed
      cataract care. METHODS: We performed a retrospective analysis of a prospectively
      maintained Medisoft EPR database of postoperative cataract review data at a
      single centre, Sligo University Hospital (SUH), which serves a large and
      predominantly rural catchment area. All patients undergoing cataract surgery at
      SUH from October 2012 to September 2013 were included in this study. A total of
      39 optometric practices, all with access to the Medisoft EPR software,
      participated in this pilot co-management scheme. RESULTS: One thousand four
      hundred and twenty-two cataract surgeries were performed in SUH (55% female, 45%
      male); 1011 patients (71%) were discharged to the community on the day of
      cataract surgery. Complete postoperative feedback (i.e. data on refraction,
      visual acuity and intraocular pressure) was available in 97% of these patients
      compared to 50% of patients reviewed in the hospital. Patients followed up by
      optometrists were twice as likely to have complete postoperative clinical details
      (RR = 1.934, 95% CI: 1.759-2.126, p < 0.0001). Overall, 65% of operations were
      performed on first eyes. Hospital doctors were more likely to document
      requirement for second eye surgery compared to community optometrists (RR =
      1.434, 95% CI: 1.302-1.580, p < 0.0001). CONCLUSIONS: Optometrists provided an
      excellent postoperative care service with superior postoperative feedback rates
      compared to hospital doctors. EPRs facilitate a postoperative shared-care pathway
      that is of high quality and efficiency with major economic advantages.

PMID- 29063357
TI  - Implementing an electronic clinical handover system in a university teaching
      hospital.
AB  - INTRODUCTION: Clinical handover is defined as inter-clinician communication
      occurring at care interfaces. In this study, we analyse the clinical outcomes and
      physician attitudes associated with the implementation of a electronic clinical
      handover system in our medical department. AIM: The aim of this project was to
      introduce a reliable, standardised, reproducible method of communicating
      information regarding inpatients within our medical department. We also sought to
      assess the attitudes of physicians within our department to medical handover.
      METHODS: We designed and implemented an electronic handover template with a
      protocol to guide staff as to its use. Handover was audited weekly. In addition,
      we surveyed attitudes of doctors to handover before and after our handover pilot.
      RESULTS: An average of 32 patients were handed over each week. Compliance with
      mandatory handover of ICU/CCU patients averaged at 59%. Extrapolating our pilot
      results for the year would result in approximately 1655 handover events per annum
      in our department. One hundred percent of physicians surveyed felt that
      documentation of handover was beneficial, and staff satisfaction with handover
      improved after initiation of the pilot (81 vs 24%, p = 0.000914). While 64% of
      staff were concerned that typed electronic handover would increase their
      workload, only 6% of the post pilot survey group felt that it did increase
      workload significantly. CONCLUSION: Electronic clinical handover is feasible and
      practical within the Irish healthcare system. In addition, it was found in our
      study to be attractive and effective to physicians without increasing their
      workload.

PMID- 29063358
TI  - Geographic distribution and incidence of Lyme borreliosis in the west of Ireland.
AB  - BACKGROUND: Lyme borreliosis is caused by Borrelia burgdorferi and is the most
      common tick-transmitted infection in temperate regions. Infection often presents
      with erythema migrans and/or other clinical features in early infection. METHODS:
      Blood samples are submitted for testing for antibodies to Borrelia burgdorferi by
      enzyme immunoassay and positive samples are confirmed by a reference laboratory
      by IgG and IgM line immune assay. A retrospective extraction of all laboratory
      requests and results for Lyme borreliosis from 2011 to 2014 was performed.
      Patient addresses were mapped to local electoral area (LEA). RESULTS: The total
      number of requests was 5049 and 242 (5%) were positive over 5 years. The number
      of positive and tested samples were 40/748, 45/905, 41/947, 73/1126 and 43/1323
      from 2011 to 2014. Even though the number of requests increased over the years,
      there was no significant increase in the number of positives. Incidences per
      100,000 population for requests and positives were calculated at LEA level and
      showed considerable variation. The highest incidence was shown in one LEA
      (Connemara) with nearly 500 requests and 43 positives per 100,000 population per
      year. CONCLUSIONS: Increased awareness may explain the increase in requests.
      There is no indication of an increase in incidence. As many GPs treat suspected
      Lyme borreliosis empirically without testing and as antibody may be undetectable
      early in the course of illness, the true incidence of infection is likely to
      exceed the number of laboratory-confirmed cases.

PMID- 29063359
TI  - Heparin, coumarin, protein C, antithrombin, fibrinolysis and other clotting
      related resistances: old and new concepts in blood coagulation.
AB  - The concept of resistance in blood coagulation has become important. In the past
      it was limited to the resistance shown by some patients to heparin, coumarin or
      aspirin. Subsequently, it was demonstrated that a mutation in a single clotting
      factor, FV, showed resistance to activated protein C. Since activated protein C
      is supposed to downregulate aFV and aFVIII, their persistence in the circulation
      gives origin to a hypercoagulable state. Recently antithrombin resistance has
      been defined. Several prothrombin abnormalities (dysprothrombinemias) have been
      shown to be resistant to the action of antithrombin. This is associated with the
      occurrence of a trombophilic state. Prothrombin may therefore be associated like
      FV with both a bleeding condition (prothrombin deficiency) and a thrombophilic
      state (some dysprothrombinemias). Finally, thrombomodulin resistance has been
      defined in liver cirrhosis. These patients often show an increased ratio between
      FVIII levels and protein C. This imbalance may be partly responsible for the
      frequent presence of portal vein thrombosis seen in these patients. All these
      studies have greatly increased the complexity of the clotting mechanisms and
      interactions. They have cast light on clinical events which had remained unknown
      or ill-defined.

PMID- 29063360
TI  - New phenanthrene and 9, 10-dihydrophenanthrene derivatives from the stems of
      Dendrobium officinale with their cytotoxic activities.
AB  - Two new phenanthrene and 9, 10-dihydrophenanthrene derivatives (1-2) with six
      known congeners (3-8) were isolated from the extraction of stems of Dendrobium
      officinale. Compounds 1 and 2 were based on carbon skeleton in which phenanthrene
      and 9, 10-dihydrophenanthrene moiety were linked with a phenylpropane unit
      through a dioxane bridge, respectively. Their structures were determined by
      comprehensive NMR spectroscopic data, the absolute configuration of new compounds
      were determined by comparing their experimental and calculated ECD for the first
      time. All the compounds were investigated contains two cancer cell lines (HI-60,
      THP-1). All the isolates showed cytotoxicity, especially compound 4 showed
      markedly cytotoxic activities against HI-60 and THP-1 cell lines with IC50 values
      of 11.96 and 8.92 MUM.

PMID- 29063361
TI  - Evaluation of raw nepodin extraction from Rumex japonicus and R. obtusifolius and
      their DNA polymorphisms.
AB  - Nepodin, found in the roots of Rumex japonicus Houtt. (Polygonaceae), inhibits
      osteoclast differentiation and has an antidiabetic effect. We propose nepodin as
      an ingredient of new functional foods or as a drug candidate for reducing the
      risk of reduced locomotion resulting from diseases such as osteoporosis. Although
      there are no previous reports of R. obtusifolius L., which is found throughout
      Japan, having roots containing nepodin, we found nepodin in the roots of this
      species. Therefore, R. obtusifolius as well as R. japonicus was considered a
      candidate raw material for nepodin extraction. We also discuss the suitability of
      R. japonicus and R. obtusifolius as sources of raw nepodin for cultivation on the
      Ryukyu Islands. In this study, all specimens on the Ryukyu Islands were
      identified as R. japonicus. Conversely, all specimens on mainland Japan were R.
      obtusifolius. The DNA sequence of the chloroplast trnL-trnF intergenic spacer
      region and partial nuclear internal transcribed spacer was consistent with the
      identification of R. japonicus and R. obtusifolius by morphological
      characteristics of the perianth segments. Therefore, to avoid erroneous
      identification and misuse of the plant species used for extraction of raw
      materials, it is preferable to develop DNA markers for these two regions. The
      content of nepodin varied from undetectable to 0.34% of the fresh weight (%FW) in
      R. japonicus and from undetectable to 0.21%FW in R. obtusifolius. From a
      pharmacological perspective, as plants that might be suitable as raw materials
      for nepodin extraction, it became clear that both R. japonicus and R.
      obtusifolius can be used with the same expected extraction efficiency. Based on
      our findings, R. obtusifolius could not be confirmed as inhabiting the Ryukyu
      Islands. For this reason, to conserve the endemic genetic characteristics of the
      Ryukyu Islands and to prevent genetic pollution by R. obtusifolius, only R.
      japonicus should be cultivated on the Ryukyu Islands.

PMID- 29063362
TI  - Piperine-like alkamides from Piper nigrum induce BDNF promoter and promote
      neurite outgrowth in Neuro-2a cells.
AB  - Black pepper (Piper nigrum) contains a variety of alkamides. Among them, piperine
      has been reported to have antidepressant-like effects in chronically stressed
      mice, but little is known about the biological activity of other alkamides. In
      this study, we investigated the effects of alkamides from white pepper (P.
      nigrum) on neuronal cells. Twelve alkamides were isolated from white pepper MeOH
      extracts, and their chemical structures were identified by NMR and MS analyses.
      The compounds were subjected to assays using the luciferase-reporter gene under
      the control of the BDNF promoter or cAMP response element in mouse neuroblastoma
      Neuro-2a cells. In both assays, marked reporter-inducing activity was observed
      for piperine (1), piperettine (2) and piperylin (7), all of which have in common
      an (E)-5-(buta-1,3-dien-1-yl)benzo[d] [1, 3] dioxole moiety. Piperettine (2) and
      piperylin (7) tended to increase endogenous BDNF protein levels. Furthermore,
      piperylin (7) promoted retinoic acid-induced neurite outgrowth. These results
      suggest that piperylin (7), or analogues thereof, may have a beneficial effect on
      disorders associated with dysregulation of BDNF expression, such as depression.

PMID- 29063363
TI  - A new cinnamoylphenethylamine derivative from a Mongolian Allium species, Allium
      carolinianum.
AB  - A new cinnamoylphenethylamine derivative, compound 1, was isolated as the main
      HPLC peak after partitioning the methanol extract of bulbs of a Mongolian onion
      species, Allium carolinianum DC. The chemical structure of this substance was
      determined by spectroscopic analysis including MS, and 1D and 2D NMR. Compound 1
      showed weak cytotoxic activity in the murine leukemia cell line P388.

PMID- 29063364
TI  - History Matters: The Critical Contribution of Historical Analysis to Contemporary
      Health Policy and Health Care.
AB  - History is popular with health policymakers, if the regularity with which they
      invoke historical anecdotes to support policy change is used as an indicator. Yet
      the ways in which they 'use' history vary enormously, as does its impact. This
      paper explores, from the perspective of a UK academic historian, the development
      of 'applied' history in health policy. It draws on personal experience of
      different types and levels of engagement with policymakers, and highlights
      mechanisms through which this dialogue and partnership can be made more
      efficient, effective, and intellectually rewarding for all involved.

PMID- 29063367
TI  - Explorations in the Aesthetic Pastoral Theology of Donald E. Capps.
AB  - This paper will examine the curative effects of art and the reorienting
      perspective of poetry in the aesthetic pastoral theology of Donald E. Capps by
      exploring two key volumes, The Poet's Gift and At Home in the World. The paper
      identifies some of the key contributions of Capps's exploration of art and poetry
      including the recovery of perception, the advancement of reframing perspective,
      the notion of embodied pastoral conversation and the roots of religious
      sensibility. The therapeutic effect of the imaginative aesthetic pastoral
      theology in these two volumes is further developed by integrating three corollary
      themes in Capps's particular orientation to pastoral theology, namely hope,
      freedom and authenticity.

PMID- 29063365
TI  - Intervertebral disc degeneration: an experimental and numerical study using a
      rabbit model.
AB  - Animal models have been extensively used for the study of degenerative diseases
      and evaluation of new therapies to stop or even reverse the disease progression.
      The aim of this study is to reproduce lumbar intervertebral disc degeneration in
      a rabbit model by performing a percutaneous annular puncture at L4L5 level. The
      effect of this damage on the spine behaviour was analysed combining three
      different techniques: imaging processing, mechanical testing and computational
      modelling. Twenty New Zealand white rabbits were divided into control and
      experimental groups and followed up during 6 months. Intervertebral disc height,
      as well as nucleus area and signal intensity, decreased with degeneration while
      storage and loss moduli increased. Both changes may be related to the loss of
      water and tissue fibrosis. Similar but slighter changes were reported for
      adjacent discs. A finite element model was built based on MRI and mechanical
      testing findings to add new biomechanical information that cannot be obtained
      experimentally. Four stages were computationally simulated representing the
      different experimental phases. The numerical simulations showed that compressive
      stresses in the damaged and adjacent discs were modified with the progression of
      degeneration. Although extrapolation to humans should be carefully made, the use
      of numerical animal models combined with an experimental one could give a new
      insight of the overall mechanical behaviour of the spine.

PMID- 29063366
TI  - Time measurement characterization of stand-to-sit and sit-to-stand transitions by
      using a smartphone.
AB  - The aim of this study is to analyze a common method to measure the acceleration
      of a daily activity pattern by using a smartphone. In this sense, a numerical
      approach is proposed to transform the relative acceleration signal, recorded by a
      triaxial accelerometer, into an acceleration referred to an inertial reference.
      The integration of this acceleration allows to determine the velocity and
      position with respect to an inertial reference. Two different kinematic
      parameters are suggested to characterize the profile of the velocity during the
      sit-to-stand and stand-to-sit transitions for Parkinson and control subjects. The
      results show that a dimensionless kinematic parameter, which is linked to the
      time of sit-to-stand and stand-to-sit transitions, has the potential to
      differentiate between Parkinson and control subjects.

PMID- 29063368
TI  - Giving Counsel: Donald Capps' Contributions to Pastoral Counseling.
AB  - This article explores some of Donald Capps' contributions to the ministry of
      pastoral counseling. In particular, several key attributes of pastoral counseling
      as a ministry of the church are identified and discussed. This is followed by
      identifying six features necessary for good enough pastoral counseling. A final
      brief section offers some musings that I wish Capps could respond to.

PMID- 29063369
TI  - Spirituality and Well-Being in Old Age: Exploring the Dimensions of Spirituality
      in Relation to Late-Life Functioning.
AB  - A growing body of research connects spirituality with positive late-life
      functioning. In this research, spirituality is often approached as a single
      measure in relation to well-being, neglecting its complex nature. Therefore, this
      study explores whether different dimensions of spirituality contribute uniquely
      to psychological well-being in advanced age. Results indicated that well-being
      was positively predicted by spirituality experienced through connectedness with
      the transcendent and through connectedness with others. Spirituality experienced
      through connectedness with nature did not predict well-being. These findings
      highlight the unique influence of each spirituality dimension on well-being as
      well as the need for a multidimensional approach.

PMID- 29063372
TI  - Obstacles to Widening Biosample Research.
AB  - Switzerland has an excellent culture of medical research and is a melting pot for
      medical experts with international expertise. Nevertheless, as in other
      countries, the resources available to medical researchers are not being fully
      used. Biological samples, which enable a host of medical research studies to be
      carried out without invasive methods involving patients, are frequently left
      unused or forgotten. The aim of this study is to examine the experiences of
      biobank stakeholders regarding the use or underuse of biosamples, in order to
      develop paths to optimize biosample research. Interviews were carried out with 36
      biobank stakeholders in Switzerland concerning their experiences with biosample
      use, and the possible obstacles at each stage of the process. Interviews revealed
      that standard operating procedures were the most frequently cited obstacle,
      although these were not judged to be severe hindrances. Despite a stated desire
      to develop biosample research, skepticism of sharing networks and wariness of new
      partnerships were strong themes. Biobanking still functions as an emerging field,
      in which exchange practices have yet to be established at the national and
      international levels. Sample exchange continues to function largely based on
      personal contacts; while this is an inherent feature of competitive medical
      research, opportunities for large-scale studies may be lost due to excessive
      caution.

PMID- 29063370
TI  - Pathways of production and delivery of hepatocyte exosomes.
AB  - Hepatocyte exosomes (ExoHep) are proposed to mediate physiological or
      pathophysiological signaling in a variety of hepatic target cells. ExoHep were
      purified from the medium of primary mouse hepatocytes or AML12 cells and
      characterized as ~100 nm nanovesicles that were positive for proteins commonly
      found in exosomes (CD9, CD81, flotillin) or hepatocytes (asialoglycoprotein
      receptor). Ethanol treatment of hepatocytes caused increased ExoHep release and
      increased cellular mRNA expression of components involved in intracellular
      vesicle trafficking (Rab 5a,b,c, Rab 7a, Rab 27a,b) or exosome biogenesis via the
      ESCRT (HGS, Alix, STAM1, TSG101, VTA1, YKT6) or ceramide (nSmase2) pathways. RNA
      interference of HGS, Alix, TSG101 or nSmase 2 caused exosome production by normal
      or ethanol-treated hepatocytes to be reduced. In mice, in vivo administration of
      fluorescently-labeled ExoHep resulted in their accumulation in the liver and
      preferential localization to hepatic stellate cells (HSC) or hepatocytes, the
      latter of which showed enhanced ExoHep binding when isolated from fibrotic mice.
      In cell co-cultures, the intercellular transfer of RNA from hepatocytes to
      hepatocytes or HSC was blocked by the exosome inhibitor GW4869. ExoHep binding to
      HSC or hepatocytes occurred via mechanisms that involved heparin-like molecules
      and cellular integrin alphav or beta1 subunits , and resulted in a reversal of
      fibrosis-associated gene expression in HSC and of ethanol-induced damage in
      hepatocytes. These studies provide insight regarding the regulation and/or
      participation of exosome biogenesis or trafficking components in hepatocytes and
      show that ExoHep can mediate therapeutic changes in activated HSC or injured
      hepatocytes that occur downstream of heparin- or integrin-dependent binding
      interactions.

PMID- 29063371
TI  - Prognostic significance of the preoperative neutrophil-to-lymphocyte ratio for
      complete resection of thymoma.
AB  - PURPOSE: The preoperative peripheral neutrophil-to-lymphocyte ratio (NLR) is
      associated with a poor prognosis for various cancers. We evaluated the prognostic
      role of the preoperative NLR in patients with thymoma. METHODS: We reviewed the
      medical records of 254 patients who underwent resection of thymic epithelial
      tumors at our institution. Patients were excluded if they had received steroid
      therapy, neoadjuvant therapy, or incomplete resection, or if they had thymic
      carcinoma or Good's syndrome, recurrence of thymoma, or missing data. The NLR was
      measured preoperatively, and outcomes of patients with a low (< 1.96) vs those
      with a high (>= 1.96) NLR were compared statistically. RESULTS: Of 159 eligible
      patients, 59 (37.1%) had a high NLR and 100 (62.9%) had a low NLR. Overall
      survival (OS), recurrence-free survival (RFS), disease-specific survival (DSS),
      disease-related survival (DRS), and the cumulative incidence of recurrence (CIR)
      differed significantly between the groups. Multivariate analyses revealed that a
      high NLR was independently associated with disease-related survival and a
      cumulative incidence of recurrence. A high NLR was also associated with a higher
      risk of recurrence of Masaoka stage I or II thymoma. CONCLUSIONS: An elevated
      preoperative NLR was associated with poor outcomes after thymoma resection. Thus,
      the NLR may be a useful biomarker of the postoperative prognosis of thymoma.

PMID- 29063373
TI  - Responses of zinc recovery to temperature and mineral composition during
      sphalerite bioleaching process.
AB  - Temperature and energy resources (e.g., iron, sulfur and organic matter) usually
      undergo dynamic changes, and play important roles during industrial bioleaching
      process. Thus, it is essential to investigate their synergistic effects and the
      changes of their independent effects with simultaneous actions of multi-factors.
      In this study, we explored the synergistic effects of temperature and original
      mineral compositions (OMCs, energy resources) on the sphalerite bioleaching
      process. The microbial community structure was monitored by 16S rRNA gene
      sequencing technology and showed clear segregation along temperature gradients
      and Shannon diversity decreased at high temperature. On the contrary, the
      physicochemical parameters (pH and [Fe3+]) in the leachate were significantly
      affected by the OMCs. Interestingly, the influence of temperature on zinc
      recovery was greater at relatively simpler OMCs level, whereas the influence of
      OMCs was stronger at lower temperature. In addition, using [Fe3+], pH, relative
      abundances of dominant OTUs of microbial community and temperature as variable
      parameters, several models were constructed to predict zinc leaching efficiency,
      providing a possibility to predict the metal recovery efficiency under
      temperature change and variable energy resources.

PMID- 29063374
TI  - Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes:
      Still a Long Way to Go?
AB  - PURPOSE OF REVIEW: Type 2 diabetes (T2D) is a complex genetic metabolic disorder.
      T2D heritability has been estimated around 40-70%. In the last decade,
      exponential progress has been made in identifying T2D genetic determinants,
      through genome-wide association studies (GWAS). Among single-nucleotide
      polymorphisms mostly associated with T2D risk, rs10830963 is located in the
      MTNR1B gene, encoding one of the two receptors of melatonin, a neurohormone
      involved in circadian rhythms. Subsequent studies aiming to disentangle the role
      of MTNR1B in T2D pathophysiology led to controversies. In this review, we will
      tackle them and will try to give some directions to get a better view of MTNR1B
      contribution to T2D pathophysiology. RECENT FINDINGS: Recent studies either based
      on genetic/genomic analyses, clinical/epidemiology data, functional analyses at
      rs10830963 locus, insulin secretion assays in response to melatonin (involving or
      not MTNR1B) or animal model analyses have led to strong controversies at each
      level of interpretation. We discuss possible caveats in these studies and present
      ways to go beyond these issues, towards a better understanding of T2D molecular
      mechanisms, keeping in mind that melatonin is a versatile hormone and regulates
      many functions via its primary role in the body clock.

PMID- 29063375
TI  - Lactic acid alleviates stress: good for female genital tract homeostasis, bad for
      protection against malignancy.
AB  - Women are unique from all other mammals in that lactic acid is present at high
      levels in the vagina during their reproductive years. This dominance may have
      evolved in response to the unique human lifestyle and a need to optimally protect
      pregnant women and their fetuses from endogenous and exogenous insults. Lactic
      acid in the female genital tract inactivates potentially pathogenic bacteria and
      viruses, maximizes survival of vaginal epithelial cells, and inhibits
      inflammation that may be damaging to the developing fetus and maintenance of the
      pregnancy. In an analogous manner, lactic acid production facilitates survival of
      malignantly transformed cells, inhibits activation of immune cells, and prevents
      the release of pro-inflammatory mediators in response to tumor-specific antigens.
      Thus, the same stress-reducing properties of lactic acid that promote lower
      genital tract health facilitate malignant transformation and progression.

PMID- 29063376
TI  - Recurrent heat shock impairs the proliferation and differentiation of C2C12
      myoblasts.
AB  - Heat-related illness and injury are becoming a growing safety concern for the
      farmers, construction workers, miners, firefighters, manufacturing workers, and
      other outdoor workforces who are exposed to heat stress in their routine lives. A
      primary response by a cell to an acute heat shock (HS) exposure is the induction
      of heat-shock proteins (HSPs), which chaperone and facilitate cellular protein
      folding and remodeling processes. While acute HS is well studied, the effect of
      repeated bouts of hyperthermia and the sustained production of HSPs in the
      myoblast-myotube model system of C2C12 cells are poorly characterized. In C2C12
      myoblasts, we found that robust HS (43  degrees C, dose/time) significantly
      decreased the proliferation by 50% as early as on day 1 and maintained at the
      same level on days 2 and 3 of HS. This was accompanied by an accumulation of
      cells at G2 phase with reduced cell number in G1 phase indicating cell cycle
      arrest. FACS analysis indicates that there was no apparent change in apoptosis
      (markers) and cell death upon repeated HS. Immunoblot analysis and qPCR
      demonstrated a significant increase in the baseline expression of HSP25, 70, and
      90 (among others) in cells after a single HS (43  degrees C) for 60 min as a
      typical HS response. Importantly, the repeated HS for 60 min each on days 2 and 3
      maintained the elevated levels of HSPs compared to the control cells. Further,
      the continuous HS exposure resulted in significant inhibition of the
      differentiation of C2C12 myocytes to myotubes and only 1/10th of the cells
      underwent differentiation in HS relative to control. This was associated with
      significantly higher levels of HSPs and reduced expression of myogenin and Myh2
      (P < 0.05), the genes involved in the differentiation process. Finally, the cell
      migration (scratch) assay indicated that the wound closure was significantly
      delayed in HS cells relative to the control cells. Overall, these results suggest
      that a repeated HS may perturb the active process of proliferation, motility, and
      differentiation processes in an in vitro murine myoblast-myotube model.

PMID- 29063377
TI  - The Relationship Between the Permeability and the Performance of Carrier-Based
      Dry Powder Inhalation Mixtures: New Insights and Practical Guidance.
AB  - The permeability of a powder bed reflects its particle size distribution, shape,
      packing, porosity, cohesivity, and tensile strength in a manner relevant to
      powder fluidization. The relationship between the permeability and the
      performance of carrier-based dry powder inhalation (DPI) mixtures has, however,
      aroused controversy. The current study sought to gain new insights into the
      relationship and to explore its potential applications. We studied eight lactose
      materials as DPI carriers. The carriers covered a broad permeability range of
      0.42-13.53 D and moreover differed in particle size distribution, particle shape,
      crystal form, and/or porosity. We evaluated the performance of inhalation
      mixtures of each of these carriers and fluticasone propionate after
      aerosolization from an Aerolizer(r), a model turbulent-shear inhaler, at a flow
      rate of 60 L/min. Starting from the high permeability side, the inhalation
      mixture performance increased as the carrier permeability decreased until optimum
      performance was reached at permeability of ~ 3.2 D. Increased resistance to air
      flow strengthens aerodynamic dispersion forces. The inhalation mixture
      performance then decreased as the carrier permeability further decreased. Very
      high resistance to air flow restricts powder dispersion. The permeability
      accounted for effects of carrier size, shape, and macroporosity on the
      performance. We confirmed the relationship by analysis of two literature
      permeability-performance datasets, representing measurements that differ from
      ours in terms of carrier grades, drug, technique used to determine permeability,
      turbulent-shear inhaler, and/or aerosolization flow rate. Permeability provides
      useful information that can aid development of DPI mixtures for turbulent-shear
      inhalers. A practical guidance is provided.

PMID- 29063378
TI  - Epidemiology of hepatitis B in pregnant Iranian women: a systematic review and
      meta-analysis.
AB  - Perinatal transmission is one of the most common routes of hepatitis B virus
      (HBV) transmission. This study aims to identify the epidemiological features of
      HBV among pregnant Iranian women. This study followed the Preferred Reporting
      Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two authors
      independently searched several online databases without time limit until May
      2017. The databases include Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus,
      PubMed, Science Direct, Cochrane, Web of Science and Google Scholar. The data
      were analyzed based on a random-effects model using Comprehensive Meta-Analysis
      software version 2. Thirty-seven studies were included in the meta-analysis. The
      prevalence of HBV among pregnant Iranian women was 1.18% (95% CI: 0.09%-1.53%).
      The prevalence of HBV among pregnant women living in urban and rural areas was
      1.60% (95% CI: 0.06%-4.30%) and 1.70% (95% CI: 0.09%-3.2%), respectively. The
      prevalence of HBV among housewives and working pregnant women was 4.3% (95% CI:
      1.4%-12.5%) and 1.2% (95% CI: 0.02%-5.8%), respectively. The risk of developing
      an HBV infection was significantly associated with illiteracy (p = 0.013),
      abortion (p = 0.001), blood transfusion (p < 0.001) and addicted spouse (p =
      0.045). However, no significant relationship was observed between HBV infection
      and urbanization (p = 0.65), occupation (p = 0.37), history of surgery (p = 0.32)
      or tattooing (p = 0.69). Vaccination coverage (receiving at least a single dose)
      in pregnant women was 9.8% (95% CI: 5.3%-17.5%). The prevalence of HBV among
      pregnant women is lower than in the general population of Iran. HBV vaccination
      coverage was low among pregnant Iranian women. Therefore, health policy-makers
      are recommended to enforce immunization programs for HBV vaccination among high
      risk pregnant women.

PMID- 29063379
TI  - Dietary Patterns and Cardiovascular Disease Risk in People with Type 2 Diabetes.
AB  - PURPOSE OF REVIEW: The primary objective of this review is to identify dietary
      patterns with beneficial effects on cardiovascular health of adults with type 2
      diabetes. RECENT FINDINGS: The prevalence of diabetes is increasing globally.
      People with diabetes have a greater risk for cardiovascular disease.
      Mediterranean diet, dietary approaches to stop hypertension diet, vegetarian
      diet, traditional Korean diet, Japanese diet, and low-glycemic-index diet can
      reduce cardiovascular disease risk in people with diabetes. Dietary intake is a
      key modifiable factor in the management of diabetes and plays a significant role
      in limiting the incidence of cardiovascular diseases.

PMID- 29063381
TI  - Push-out bond strength of three different calcium silicate-based root-end filling
      materials after ultrasonic retrograde cavity preparation.
AB  - OBJECTIVE: The aim of this study was to evaluate the bond strength of three
      calcium silicate-based root-end filling materials. MATERIALS AND METHODS: The
      root canals of 30 single-rooted teeth were endodontically treated; their root
      ends were resected and root-end cavities were prepared using ultrasonic tip. The
      teeth were randomly divided into three groups according to the material: (1)
      Micro-Mega mineral trioxide aggregate (MM-MTA), (2) Biodentine, and (3) TotalFill
      root repair material (RRM). Push-out test was performed using universal testing
      machine, and failure mode was analyzed by stereomicroscope. The data were
      statistically analyzed using Kruskal-Wallis and Man-Whitney post hoc tests. All p
      values < 0.05 were considered significant. RESULTS: TotalFill RRM exhibited
      significantly higher bond strength (12.69 MPa) than Biodentine (9.34 MPa, p =
      0.023) and MM-MTA (7.89 MPa, p = 0.002). The difference between Biodentine and MM
      MTA was not significant (p = 0.447). Mixed failures were the most noted in all
      three groups. MM-MTA had more adhesive failures than Biodentine and TotalFill,
      and no cohesive failures, but without statistical significance (p = 0.591).
      CONCLUSION: The bond strength was the highest for TotalFill RRM. CLINICAL
      RELEVANCE: In order to provide a persistent apical seal, root-end filling
      materials should resist dislodgement under static conditions, during function and
      operative procedures. TotalFill RRM exhibited higher bond strength to dentin than
      MM-MTA and Biodentine.

PMID- 29063382
TI  - Relationship between anterior mandibular bone thickness and the angulation of
      incisors and canines-a CBCT study.
AB  - OBJECTIVES: The morphology of the maxillary and mandibular alveolar cortex plays
      an important role in the planning of orthodontic treatment. Cone-beam computed
      tomography (CBCT) provides a precise demonstration of anatomical structures.
      Therefore, the aim of this paper was to evaluate what influence the position of
      incisors and canines have on the dimensions of the cortical and spongious bone of
      the anterior mandibular alveolar process. MATERIALS AND METHODS: The material
      consisted of 100 CBCT volumes (61 females and 39 males, aged 18-71 years)
      obtained by means of a Gendex GXCB-500 machine and analysed using i-CAT Vision
      and CorelDRAW 9 software. Several linear and angular measurements were taken of
      cortical and spongious mandibular, vestibular and lingual alveolar bone. RESULTS:
      The thickness of the vestibular spongious bone increased around lateral incisors
      and canines together with dental axis inclination, as did the thickness of the
      lingual spongious bone around central incisors and canines with greater angles of
      vestibular cortex curvature. In all teeth, the thickness of lingual cancellous
      bone decreased along with increase of the angle of tooth inclination. In the case
      of almost all groups of teeth, the thickness of lingual cancellous bone around
      teeth declined as the angle of curvature of the cortical bone decreased. The
      rotation of mandibular incisors and canines did not affect the thickness of the
      surrounding bone. CONCLUSIONS: The position of teeth has little influence on
      vestibular bone thickness and is only significant around central incisors. In the
      case of almost all groups of teeth, the thickness of lingual spongious bone
      around teeth declined as the angle of curvature of the cortical bone decreased.
      CLINICAL RELEVANCE: CBCT is a diagnostic tool that provides detailed information
      on the dimensions of the anterior dentate mandibular alveolar process.

PMID- 29063383
TI  - Risk factors associated with new caries lesions in permanent first molars in
      children: a 5-year historical cohort follow-up study.
AB  - OBJECTIVE: The objective of this study is to analyze the factors associated with
      the occurrence of caries in the permanent teeth (PT) and in the permanent first
      molar (PFM) 5 years after their eruption. MATERIAL AND METHODS: Children born in
      2005 and enrolled in a community dental program were included. The inclusion
      criteria were: age 10 years in 2015; the availability of clinical dental history
      (CDH) data from before eruption of the PT and a follow-up period of 5 years after
      eruption of the PT. A total of 206 children were enrolled. Risk factors evaluated
      were: caries experience in the mother, educational level of the mother, frequent
      drug use, systemic diseases, eating habits, brushing frequency, presence of molar
      incisor hypomineralization (MIH) in PT, and caries in deciduous teeth (DT).
      Associations between explanatory factors and the DMF-T (decayed, missing, filled
      teeth in PT) and DMFT-M (DMF in PFM) indexes, independently considering cavitated
      or cavitated and non-cavitated caries as outcomes, were evaluated by poisson
      regression with robust variance analysis. RESULTS: In the multivariate analysis,
      a cariogenic diet, especially soft drinks, was associated to high DMF-T and DMFT
      M scores when both cavitated and non-cavitated caries were considered. A brushing
      frequency < 1 a day was significantly associated to high DMF-T scores. The
      presence of df-t (decayed and filled temporary teeth) score > 0 and MIH
      conditioned high DMF-T or DMFT-M values, considering cavitated or cavitated and
      non-cavitated caries. CONCLUSIONS: The intake of sweets and soft drinks, brushing
      frequency, caries in DT, and MIH in PT were the best predictors of caries in PT.
      CLINICAL RELEVANCE: Control of risk factors in early childhood is important for
      preventing caries in PT.

PMID- 29063380
TI  - What Twin Studies Tell Us About Brain Responses to Food Cues.
AB  - PURPOSE OF REVIEW: Functional magnetic resonance imaging (fMRI) using visual food
      cues provides insight into brain regulation of appetite in humans. This review
      sought evidence for genetic determinants of these responses. RECENT FINDINGS:
      Echoing behavioral studies of food cue responsiveness, twin study approaches
      detect significant inherited influences on brain response to food cues. Both
      polygenic (whole genome) factors and polymorphisms in single genes appear to
      impact appetite regulation, particularly in brain regions related to satiety
      perception. Furthermore, genetic confounding might underlie findings linking
      obesity to stereotypical response patterns on fMRI, i.e., associations with
      obesity may actually reflect underlying inherited susceptibilities rather than
      acquired levels of adiposity. Insights from twin studies show that genes
      powerfully influence brain regulation of appetite, emphasizing the role of
      inherited susceptibility factors in obesity risk. Future research to delineate
      mechanisms of inherited obesity risk could lead to novel or more targeted
      interventional approaches.

PMID- 29063384
TI  - Peroxiredoxin I expression in epithelial cells of buccal mucosa from patients
      exposed to panoramic X-rays: influence of the age.
AB  - OBJECTIVES: The aim of this study was to evaluate peroxiredoxin I (Prx I)
      participation in the cellular antioxidant response to low-dose X-rays through the
      analysis of its expression in buccal mucosa cells from patients of different ages
      following panoramic dental radiography. MATERIALS AND METHODS: Of the 50 patients
      included in this study, oral mucosa cells from six adults were collected for the
      immunofluorescence cytological analysis. The other 44 patients, 11 patients aged
      below 20 years; 22 patients aged between 20 and 50 years; and 11 patients aged
      above 50 years, were submitted to panoramic dental radiography, and oral mucosa
      cells were collected for the gene expression analysis before and 1 hour after
      exposure. RESULTS: The results demonstrated Prx I expression in the cytoplasm of
      oral mucosa cells either before or after radiation exposure. The quantitative
      analysis showed that in oral mucosa cells from patients aged below 50 years the
      mRNA levels of PRDX1 were significantly increased after radiation exposure. On
      the other hand, the cells from patients aged above 50 years presented
      significantly lower PRDX1 transcript levels after radiation exposition.
      CONCLUSIONS: Panoramic radiography leads to increased Prx I expression in buccal
      mucosa cells, probably as an adaptive response to eliminate X-ray-induced ROS,
      except in cells from elderly people. CLINICAL RELEVANCE: Even low doses of
      radiation employed for dental purposes are capable to provoke stress to cells,
      which was demonstrated via the induction of the antioxidant gene PRDX1. In
      elderly patients, such mechanism was demonstrated to be impaired.

PMID- 29063385
TI  - Does smoking habit increase the micronuclei frequency in the oral mucosa of
      adults compared to non-smokers? A systematic review and meta-analysis.
AB  - OBJECTIVES: A systematic review of clinical studies to evaluate the frequency of
      micronuclei in the oral mucosa of smokers and non-smokers in adult patients was
      performed. MATERIALS AND METHODS: A comprehensive search was carried out on
      MEDLINE via PubMeb, Scopus, Web of Science, LILACS, BBO, and Cochrane Library and
      SIGLE without restrictions. Dissertations and thesis were searched using the
      ProQuest Dissertations and Periodicos Capes Thesis Databases. We included only
      cross-sectional clinical trials that compared the frequency of micronuclei in the
      oral mucosa of smokers and non-smokers in adult patients. DATA: After the removal
      of duplicates, 1338 articles were identified. After title and abstract screening,
      35 studies remained. Eighteen studies were further excluded, whereas 17 studies
      remained for qualitative analysis and 16 for the meta-analysis of the primary and
      secondary outcomes. A significant difference in the frequency of micronuclei in
      smokers when compared to non-smokers was observed in the present study.
      CONCLUSIONS: Despite the high variation in the methodology of the assessed
      studies, this study showed a higher frequency of micronuclei in exfoliated cells
      of smokers compared to non-smokers. CLINICAL SIGNIFICANCE: The use of tobacco is
      associated with cytotoxic and genotoxic effects because a higher frequency of
      micronuclei in exfoliated cells of smokers was observed.

PMID- 29063387
TI  - Erratum to: Accounting for thermodynamic non-ideality in the Guinier region of
      small-angle scattering data of proteins.
AB  - The article "Accounting for thermodynamic non-ideality in the Guinier region of
      small-angle scattering data of protein", written by David J. Scott, was
      originally published without open access.

PMID- 29063386
TI  - Assessment of immune organ dysfunction in critical illness: utility of innate
      immune response markers.
AB  - In critically ill patients, organ dysfunctions are routinely assessed, monitored,
      and treated. Mounting data show that substantial critical illness-induced changes
      in the immune system can be observed in most ICU patients and that not only
      "hyper-inflammation" but also persistence of an anti-inflammatory phenotype (as
      in sepsis-associated immunosuppression) is associated with increased morbidity
      and mortality. Despite common perception, changes in functional immunity cannot
      be adequately assessed by routine inflammatory biomarkers such as C-reactive
      protein, procalcitonin, or numerical analysis of leukocyte (sub)-counts.
      Cytokines appear also not suited due to their short half-life and pleiotropy,
      their unexclusive origin from immune cells, and their potential to undergo
      antagonization by circulating inactivating molecules. Thus, beyond leukocyte
      quantification and use of routine biomarkers, direct assessment of immune cell
      function seems required to characterize the immune systems' status. This may
      include determination of, e.g., ex vivo cellular cytokine release, phagocytosis
      activity, and/or antigen-presenting capacity. In this regard, standardized flow
      cytometric assessment of the major histocompatibility-II complex human leukocyte
      antigen (-D related) (HLA-DR) has gained particular interest. Monocytic HLA-DR
      (mHLA-DR) controls the interplay between innate and adaptive immunity and may
      serve as a "global" biomarker of injury-associated immunosuppression, and its
      decreased expression is associated with adverse clinical outcomes (e.g.,
      secondary infection risk, mortality). Importantly, recent data demonstrate that
      injury-associated immunosuppression can be reversed-opening up new therapeutic
      avenues in affected patients. Here we discuss the potential scientific and
      clinical value of assessment of functional immunity with a focus on
      monocytes/macrophages and review the current state of knowledge and potential
      perspectives for affected critically ill patients.

PMID- 29063388
TI  - Utilization of agents to prevent skeletal-related events among patients with
      multiple myeloma: analysis of real-world data.
AB  - PURPOSE: This study examined real-world utilization patterns of bone-targeted
      agents (BTA) in patients with multiple myeloma (MM). METHODS: In this
      retrospective cohort study, adults with an MM diagnosis recorded in 2012-2014
      were identified from electronic health records in the Oncology Services
      Comprehensive Electronic Records (OSCER) database. Patients received zoledronic
      acid (ZA) or pamidronate (PA) on/after first MM diagnosis recorded in the study
      period, had no BTA use in prior 6 months, and were followed through earliest of
      May 31, 2015 or last clinic visit. Patients with any solid tumor diagnosis were
      excluded. Time to BTA initiation, compliance (>= 12 administrations in a year),
      switching, and non-persistence (switch or >= 90-day gap in therapy) were
      described by agent and follow-up period. RESULTS: Among 9,617 patients with MM,
      3,735 (38.8%) received a BTA. Most patients (90.9%) received ZA, with first BTA
      use generally seen within 3 months of first observed MM diagnosis (ZA 76.1%, PA
      75.1%). A minority of ZA (27.4%) and PA (23.0%) patients were compliant in Year
      1, with lower compliance in Year 2 (19.8% and 15.6%, respectively). The median
      time to non-persistence was 16.2 (95% confidence interval [CI] 15.4-17.4) months
      for ZA and 13.8 (95% CI 11.5-15.4) months for PA. Persistence was 86% at 6 months
      and 34% at 24 months for ZA, and 77% and 30% for PA, respectively. CONCLUSIONS:
      These results highlight the possibility of suboptimal prevention of skeletal
      related events due to non-compliant dosing and non-persistence after patients
      initiate BTA therapy.

PMID- 29063389
TI  - Building psychosocial capacity through training of front-line health
      professionals to provide brief therapy: lessons learned from the PROMPT study.
AB  - PURPOSE: This report describes the views of front-line health professionals who
      participated in a randomised controlled trial examining a model of care in which
      depressed cancer patients received a brief psychosocial intervention. Health
      professionals from four cancer centres received focused training, skill
      development and clinical supervision in order to deliver the intervention.
      METHODS: We interviewed 20 health professionals asking them about their
      perceptions of participation in the study and their views about more widespread
      implementation of this model of care. RESULTS: Participants strongly advocated
      for widespread implementation of this model of care; however, their ability to
      deliver the intervention varied depending on clinical roles and responsibilities.
      Many oncology nurses expressed conflict about delivering a psychosocial
      intervention when their clinical unit was busy. Finding a private area in which
      to talk was a frequent barrier in busy clinical units. Participants reported that
      they applied the skills and insights acquired in the study in their routine
      clinical work. Supervision was highly valued and was feasible to provide in
      clinical settings. CONCLUSION: Psychosocial care can be provided by a range of
      health professionals if they receive focused training and have access to
      supervision, but competing clinical demands are likely to limit their ability to
      routinely provide psychosocial care. This suggests that training should target
      professionals who have greater autonomy and flexibility in their work roles.
      TRIAL REGISTRATION NUMBER: ANZCTR1260000448044.

PMID- 29063390
TI  - Comparison of quality of life between 2-year and 3-or-more-year administration of
      leuprorelin acetate every-3-months depot in combination with tamoxifen as
      adjuvant endocrine treatment in premenopausal patients with endocrine-responsive
      breast cancer: a randomized controlled trial.
AB  - BACKGROUND: We conducted an open-label, randomized controlled trial evaluating
      the appropriate treatment duration of leuprorelin acetate 3-month depot, TAP-144
      SR (3M), administered postsurgically every 3 months for 2 years versus 3 or more
      (up to 5) years, in combination with tamoxifen, for 5 years in premenopausal
      endocrine-responsive breast cancer patients and reported similar survival benefit
      in the two treatment groups. We hereby present patient-reported quality of life
      (QOL) data obtained from this trial. METHODS: Three self-administered QOL
      questionnaires (QOL-ACD, QOL-ACD-B, FACT-ES subscale) were used, and the
      difference in QOL score changes between the two groups was analyzed using a mixed
      effects model for repeated measures. RESULTS: Eligible patients (N = 222) were
      randomly assigned to a 2-year (2YG, N = 112) or 3-or-more-year treatment group
      (3YG, N = 110). The time courses of the three QOL scores during the trial period
      were similar in the two groups. The mean changes in the QOL scores from week 96
      were largely stable through week 240 in the 3YG, but showed significantly greater
      improvement in the score changes from week 96 in the 2YG than the 3YG. Symptoms
      associated with menopause such as hot flashes and sweating contributed to these
      results. Menstruation recovery was associated with significantly greater
      improvement of these symptoms in the 2YG than the 3YG. CONCLUSIONS: Patient
      reported menopause-associated symptoms and QOL improved after discontinuation of
      the LH-RH agonist administration and menstruation recovery. QOL information
      should be a consideration in long-term treatment.

PMID- 29063391
TI  - Degradation of atenolol via heterogeneous activation of persulfate by using
      BiOCl@Fe3O4 catalyst under simulated solar light irradiation.
AB  - Efficient oxidative degradation of pharmaceutical pollutants in aquatic
      environments is of great importance. This study used magnetic BiOCl@Fe3O4
      catalyst to activate persulfate (PS) under simulated solar light irradiation.
      This degradation system was evaluated using atenolol (ATL) as target pollutant.
      Four reactive species were identified in the sunlight/BiOCl@Fe3O4/PS system. The
      decreasing order of the contribution of each reactive species on ATL degradation
      was as follows: h+ ~ HO. > O2.- > SO4.-. pH significantly influenced ATL
      degradation, and an acidic condition favored the reaction. High degradation
      efficiencies were obtained at pH 2.3-5.5. ATL degradation rate increased with
      increased catalyst and PS contents. Moreover, ATL mineralization was higher in
      the sunlight/BiOCl@Fe3O4/PS system than in the sunlight/BiOCl@Fe3O4 or
      sunlight/PS system. Nine possible intermediate products were identified through
      LC-MS analysis, and a degradation pathway for ATL was proposed. The BiOCl@Fe3O4
      nanomagnetic composite catalyst was synthesized in this work. This catalyst was
      easily separated and recovered from a treated solution by using a magnet, and it
      demonstrated a high catalytic activity. Increased amount of the BiOCl@Fe3O4
      catalyst obviously accelerated the efficiency of ATL degradation, and the
      reusability of the catalyst allowed the addition of a large dosage of BiOCl@Fe3O4
      to improve the degradation efficiency.

PMID- 29063392
TI  - Prokaryotic community profiling of local algae wastewaters using advanced 16S
      rRNA gene sequencing.
AB  - Algae biomass-fed wastewaters are a promising source of lipid and bioenergy
      manufacture, revealing substantial end-product investment returns. However,
      wastewaters would contain lytic pathogens carrying drug resistance detrimental to
      algae yield and environmental safety. This study was conducted to simultaneously
      decipher through high-throughput advanced Illumina 16S ribosomal RNA (rRNA) gene
      sequencing, the cultivable and uncultivable bacterial community profile found in
      a single sample that was directly recovered from the local wastewater systems.
      Samples were collected from two previously documented sources including
      anaerobically digested (AD) municipal wastewater and swine wastewater with algae
      namely Chlorella spp. in addition to control samples, swine wastewater, and
      municipal wastewater without algae. Results indicated the presence of a
      significant level of Bacteria in all samples with an average of approximately
      95.49% followed by Archaea 2.34%, in local wastewaters designed for algae
      cultivation. Taxonomic genus identification indicated the presence of Calothrix,
      Pseudomonas, and Clostridium as the most prevalent strains in both local
      municipal and swine wastewater samples containing algae with an average of 17.37,
      12.19, and 7.84%, respectively. Interestingly, swine wastewater without algae
      displayed the lowest level of Pseudomonas strains < 0.1%. The abundance of some
      Pseudomonas species in wastewaters containing algae indicates potential
      coexistence between these strains and algae microenvironment, suggesting further
      investigations. This finding was particularly relevant for the earlier documented
      adverse effects of some nosocomial Pseudomonas strains on algae growth and their
      multidrug resistance potential, requiring the development of targeted
      bioremediation with regard to the beneficial flora.

PMID- 29063394
TI  - Multivariate curve resolution of organic pollution patterns in mangrove forest
      sediment from Qeshm Island and Khamir Port-Persian Gulf, Iran.
AB  - Straight-chain alkanes (n-alkanes) have been proposed as biomarkers to assess
      petroleum pollution sources in marine environments. In this work, three sampling
      sites were selected along Iranian-protected mangrove forests in the Persian Gulf.
      Sample sites were chosen to represent different compositions and sources of n
      alkanes in surface sediments (0-5 cm) from different locations in the Khamir
      Port, in the middle part of the Gulf, and in the Qeshm Island. Samples were
      analyzed by gas chromatography-mass spectrometry (GC-MS), and the obtained n
      alkanes concentrations were analyzed by principal component analysis (PCA) and
      multivariate curve resolution alternating least squares (MCR-ALS) to deduce their
      possible sources and distribution patterns. Results revealed that n-alkanes have
      a dominant biogenic source in marginal Qeshm Island stations, which changed from
      biogenic to petrogenic sources in the Khamir Port areas. Sediment samples from
      the Khamir Port showed the significant presence of oil pollution due to
      transportation. These samples are being exposed to basic Persian Gulf currents
      entering from the Hormuz Strait causing oil pollution spread over the entire Gulf
      area. Sediment samples of the Middle Part stations located between two other
      sites show a combined condition of the two previous sections, with petrogenic and
      biogenic contributions. The present study demonstrates that the Hara Protected
      Area was already contaminated by background oil pollution as a result of
      continuous oil spills and war conflicts in the Persian Gulf.Additionally, the MCR
      ALS method is shown to be a powerful chemometric tool for the investigation,
      resolution, identification, and description of pollution patterns distributed
      over a particular geographical area and environmental compartment. They can be
      used as well as parameters like unresolved to resolved ratio (U/R), pristane to
      phytane (Pr/Ph), n-C17/Pr, n-C18/Ph, and unresolved complex mixture (UCM) to
      assess petroleum pollution sources in the sediments.

PMID- 29063393
TI  - Corn industrial wastewater (nejayote): a promising substrate in Mexico for
      methane production in a coupled system (APCR-UASB).
AB  - In Mexico, the corn tortilla is a food of great economic importance. Corn
      tortilla production generates about 1500-2000 m3 of wastewater per 600 tons of
      processed corn. Although this wastewater (also known as nejayote) has a high
      organic matter content, few studies in Mexico have analyzed its treatment. This
      study presents fresh data on the potential methane production capacity of
      nejayote in a two-phase anaerobic digestion system using an Anaerobic-Packed
      Column Reactor (APCR) to optimize the acidogenic phase and an up-flow anaerobic
      sludge blanket (UASB) reactor to enhance the methanogenic process. Results
      indicate that day 8 was ideal to couple the APCR to the UASB reactor. This
      allowed for a 19-day treatment that yielded 96% COD removal and generated a
      biogas containing 84% methane. The methane yield was 282 L kg-1 of CODremoved.
      Thus, two-phase anaerobic digestion is an efficient process to treat nejayote;
      furthermore, this study demonstrated the possibility of using an industrial
      application by coupling the APCR to the UASB reactor system, in order to assess
      its feasibility for biomethane generation as a sustainable bioenergy source.

PMID- 29063395
TI  - Combined effects of binary antibiotic mixture on growth, microcystin production,
      and extracellular release of Microcystis aeruginosa: application of response
      surface methodology.
AB  - The interactive effects of binary antibiotic mixtures of spiramycin (SP) and
      ampicillin (AMP) on Microcystis aeruginosa (MA) in terms of growth as well as
      microcystin production and extracellular release were investigated through the
      response surface methodology (RSM). SP with higher 50 and 5% effective
      concentrations in MA growth was more toxic to MA than AMP. RSM model for toxic
      unit approach suggested that the combined toxicity of SP and AMP varied from
      synergism to antagonism with SP/AMP mixture ratio decreasing from reversed
      equitoxic ratio (5:1) to equitoxic ratio (1:5). Deviations from the prediction of
      concentration addition (CA) and independent action (IA) model further indicated
      that combined toxicity of target antibiotics mixed in equivalent ratio (1:1)
      varied from synergism to antagonism with increasing total dose of SP and AMP.
      With the increase of SP/AMP mixture ratio, combined effect of mixed antibiotics
      on MA growth changed from stimulation to inhibition due to the variation of the
      combined toxicity and the increasing proportion of higher toxic component (SP) in
      the mixture. The mixture of target antibiotics at their environmentally relevant
      concentrations with increased total dose and SP/AMP mixture ratio stimulated
      intracellular microcystin synthesis and facilitated MA cell lysis, thus leading
      to the increase of microcystin productivity and extracellular release.

PMID- 29063396
TI  - Purification of Hg0 from flue gas by wet oxidation method and its mechanism: a
      review.
AB  - The vast majority of Hg2+ can be removed while elemental mercury (Hg0) can hardly
      be removed due to its characteristic of high volatility and insolubility in
      water. Till now, how to oxidize Hg0 to Hg2+ is the key for the purification of
      Hg0, especially when there are others pollutants, such as HCl, SO2, and NOx. In
      this review, the method and mechanism of Hg0 purification from flue gas by H2O2,
      KMnO4, NaClO2, and O3 are reviewed comprehensively. It is concluded that the
      oxidation of Hg0 mainly depends on the electronic supply efficiency from the
      solution. The Fenton reagent, composed of H2O2 and metal cations, is superior to
      O3 and the solution of KMnO4 and NaClO2. Moreover, HCl, SO2, and NOx in the flue
      gas can influence the oxidation and purification mechanism of Hg0. It is found
      that HCl in flue gas had obvious auxo-action on the oxidation of mercury, and SO2
      and NOx have different effects on the oxidation of Hg0 with the change of
      compositions and concentration of pollutants in the flue gas. In general, SO2 and
      NOx can slightly promote the oxidation of Hg0 due to the synergistic effect.

PMID- 29063397
TI  - Effect of zero-valent iron and trivalent iron on UASB rapid start-up.
AB  - In order to realize the rapid start-up of upflow anaerobic sludge blanket (UASB)
      reactor, the iron ion in different valence state was added to UASB. The results
      indicated that the start-up time of R3 (FeCl3) was 48 h faster than that of R2
      (zero-valent iron (ZVI)). It was because the FeCl3 could rapidly promote
      granulation of sludge as a flocculant. However, ZVI released Fe2+ through
      corrosion slowly, and then the Fe2+ increased start-up speed by enhancing enzyme
      activity and enriching methanogens. In addition, the ZVI and FeCl3 could promote
      hydrolysis acidification and strengthen the decomposition of long-chain fatty
      acids. The detection of iron ions showed that iron ions mainly existed in the
      sludge. Because the high concentration of Fe2+ could inhibit anaerobic bacteria
      activity, excess Fe3+ could be changed into iron hydroxide precipitation to
      hinder the mass transfer process of anaerobic bacteria under the alkaline
      condition. The FeCl3 was suitable to be added at the initial stage of UASB start
      up, and the ZVI was more fitted to be used in the middle stage of reactor start
      up to improve the redox ability.

PMID- 29063398
TI  - Macroinvertebrate communities in riverine systems of buffer areas of protected
      wildland, rangeland and city areas: implications for conservation of riverine
      systems on urbanising watersheds.
AB  - Riverine systems in developing countries continue to be degraded by anthropogenic
      pressures such as urbanisation. The responses of biota in watersheds surrounding
      a drainage divide may provide critical information that is required to protect
      the ecological condition of riverine systems. This study assessed the spatial
      variation of selected environmental variables together with macroinvertebrate
      communities in upper reaches of riverine systems across different land use
      categories of the Bulawayo region. Based on an a priori selection criterion,
      studied sites were grouped following an urban-wastewater disturbance gradient
      comprising of (i) heavily polluted city sites, (ii) moderately disturbed
      rangeland sites and (iii) less disturbed sites of the buffer areas of protected
      wildland. Most of the studied environmental variables and the macroinvertebrate
      community assemblages were significantly (ANOVA, p < 0.05) different and degraded
      within the city areas. In this study, the variance of environmental variables
      known to be associated with organic pollution like increased nutrients,
      embeddedness by particulates, salinity, COD, conductivity, turbidity and reduced
      dissolved oxygen was found to be related with the variation of macroinvertebrate
      communities across the studied sites. Besides affirming the effectiveness of
      macroinvertebrate-based bioassessment approaches, the results of our study
      demonstrate that an aggressive riverine protection policy that prohibits the
      discharge of poor-quality urban effluents and preservation of the less disturbed
      riverine systems needs to be part of the larger urban planning and regulatory
      framework in urbanising watersheds.

PMID- 29063399
TI  - Photocatalytic degradation of organic pollutant aldicarb by non-metal-doped
      nanotitania: synthesis and characterization.
AB  - The current study focused on pollution control by titania through photocatalytic
      degradation of aldicarb pesticide in aqueous medium. Titania, which is an
      efficient photocatalyst, can bring about degradation of aqueous organic
      pollutants under UV and visible light irradiation. Here, we prepared titania by
      sol-gel method from titanium tetraisopropoxide and doped non-metals like N and S
      from sources such as urea and thiourea, respectively. The prepared catalyst was
      characterized by XRD, UV-Vis.DRS, TEM, XPS, etc. Photocatalytic activity of the
      catalyst was evaluated from extend of degradation of aldicarb pesticide by
      measuring its concentration with the help of HPLC. It was found that the modified
      catalyst showed better photocatalytic degradation than pure titania in visible
      light.

PMID- 29063400
TI  - Occurrence of multi-class surfactants in urban wastewater: contribution of a
      healthcare facility to the pollution transported into the sewerage system.
AB  - Healthcare facility discharges, by their nature, are often considered as non
      domestic effluent, which can provide significant pollution comparatively to other
      domestic sources. In this context, a total of 12 monthly sampling campaigns were
      collected from a healthcare facility as well as the output of a sewerage system
      of Site Pilote de Bellecombe (SIPIBEL) observatory. This study focuses more
      specifically on 12 surfactants and biocides: four anionics, four cationic, two
      non-ionic, one zwitterionic, and one dispersive agent, among the most commonly
      used commercial surfactants. Particular attention was also provided to routine
      wastewater quality parameters. Both effluents were heavily contaminated by most
      anionic surfactants; they displayed median concentrations up to 1 to 2 mg/L for
      linear alkylbenzene sulfonates and between 10 and 100 MUg/L for other sodium
      sulfate congeners (lauryl and laureth). Overall, for the majority of surfactants,
      the healthcare facility contribution to the total flux reaching the wastewater
      treatment plant ranges between 5 and 9%.

PMID- 29063401
TI  - Biofilm formation is determinant in tomato rhizosphere colonization by Bacillus
      velezensis FZB42.
AB  - In this work, the behavior in tomato rhizosphere of Bacillus velezensis FZB42 was
      analyzed taking into account the surfactin production, the use of tomato roots
      exudate as substrates, and the biofilm formation. B. velezensis FZB42 and B.
      amyloliquefaciens S499 have a similar capability to colonize tomato rhizosphere.
      Little difference in this colonization was observed with surfactin non producing
      B. velezensis FZB42 mutant strains. B. velezensis is able to grow in the presence
      of root exudate and used preferentially sucrose, maltose, glutamic, and malic
      acids as carbon sources. A mutant enable to produce exopolysaccharide (EPS-) was
      constructed to demonstrate the main importance of biofilm formation on
      rhizosphere colonization. This mutant had completely lost its ability to form
      biofilm whatever the substrate present in the culture medium and was unable to
      efficiently colonize tomato rhizosphere.

PMID- 29063402
TI  - Existing forms and changes of nitrogen inside of horizontal subsurface
      constructed wetlands.
AB  - Horizontal zeolite subsurface constructed wetland system (HZCWs) and horizontal
      limestone subsurface constructed wetland system (HLCWs) were applied to the
      removal of nitrogen in lightly polluted wastewater, and the existing forms,
      changes, and removal mechanism of nitrogen in the constructed wetlands were
      analyzed. The results indicated that compared with HLCWs, HZCWs exhibited better
      nitrogen removal effect, and the maximum removal rates of ammonia nitrogen and
      total nitrogen could reach 96.97 +/- 5.29 and 93.12 +/- 3.35%, respectively.
      Besides, analysis of the removal effect on nitrogen in different existing forms
      on different substrate heights in the constructed wetlands showed that variation
      of nitrogen removal efficiency had certain regularities, which were related to
      the interior construction features of the wetland systems, and agreed with the
      regularities in the changes of the influential factors such as DO inside of the
      wetlands. In addition, degradation mechanism of pollutions was also analyzed, and
      the results indicated that the quantity of microorganisms and enzymes, including
      FDA, catalase, and urease, on the surface of the substrates had significant
      influence on the removal regularities and effects of the major pollutions in
      constructed wetlands.

PMID- 29063403
TI  - Relay cropping of wheat (Triticum aestivum L.) in cotton (Gossypium hirsutum L.)
      improves the profitability of cotton-wheat cropping system in Punjab, Pakistan.
AB  - Delayed sowing of wheat (Triticum aestivum L.) in cotton-based system reduces the
      productivity and profitability of the cotton-wheat cropping system. In this
      scenario, relay cropping of wheat in standing cotton might be a viable option to
      ensure the timely wheat sowing with simultaneous improvement in wheat yields and
      system profitability. This 2-year study (2012-2013 and 2013-2014) aimed to
      evaluate the influence of sowing dates and relay cropping combined with different
      management techniques of cotton sticks on the wheat yield, soil physical
      properties, and the profitability of the cotton-wheat system. The experiment
      consisted of five treatments viz. (S1) sowing of wheat at the 7th of November by
      conventional tillage (two disc harrows + one rotavator + two plankings) after the
      removal of cotton sticks, (S2) sowing of wheat at the 7th of November by
      conventional tillage (two disc harrows + two plankings) after the incorporation
      of cotton sticks in the field with a rotavator, (S3) sowing of wheat at the 7th
      of November as relay crop in standing cotton with broadcast method, (S4) sowing
      of wheat at the 15th of December by conventional tillage (two disc harrows + one
      rotavator + two plankings) after the removal of cotton sticks, and (S5) sowing of
      wheat at the 15th of December by conventional tillage (two disc harrows + two
      plankings) after the incorporation of cotton sticks in the field with a
      rotavator. The highest seed cotton yield was observed in the S5 treatment which
      was statistically similar with the S3 and S4 treatments; seed cotton yield in the
      S1 and S2 treatments has been the lowest in both years of experimentation.
      However, the S2 treatment produced substantially higher root length, biological
      yield, and grain yield of wheat than the other treatments. The lower soil bulk
      density at 0-10-cm depth was recorded in the S2 treatment which was statistically
      similar with the S5 treatment during both years of experimentation. The
      volumetric water contents, net benefit, and benefit-cost ratio were the highest
      in the S3 treatment during both years of experimentation. Thus, relay cropping of
      wheat in standing cotton might be a viable option to improve the soil physical
      environment and profitability of the cotton-wheat cropping system.

PMID- 29063404
TI  - Isolation and characterization of culturable bacteria present in the spent
      nuclear fuel pool water.
AB  - A spent nuclear fuel (SNF) pool is a key facility for safe management of nuclear
      waste, where spent nuclear fuel rods are stored in a water pool. The spent fuel
      rods carry a significant amount of radioactivity; they are either recycled or
      stored for further processing. Pool water acts as a heat sink as well as a shield
      against the radiation present in spent/burned fuel rods. The water used in these
      pools is filtered by an ultra-filtration process which makes certain the purity
      of water. As the life span of these pools is approximately 20 to 40 years, the
      maintenance of pure water is a big challenge. A number of researchers have shown
      the presence of bacterial communities in this ultrapure water. The bacterial
      types present in SNF pool water is of increasing interest for their potential
      bioremediation applications for radioactive waste. The present study showed the
      isolation of six bacterial species in the SNF pool water samples, which had
      significant radio-tolerance (D10 value 248 Gy to 2 kGy) and also biofilm-forming
      capabilities. These strains were also investigated for their heavy metal removal
      capacity. Maximum biofilm-mediated heavy metal (Co and Ni) removal (up to 3.8
      MUg/mg of biomass) was observed by three isolates (FPB1, FPB4, and FPB6). The
      ability of these bacterial isolates to survive in radioactive environments can be
      of great interest for remediation of radioactive contaminants.

PMID- 29063405
TI  - The impact of foreign direct investment on CO2 emissions in Turkey: new evidence
      from cointegration and bootstrap causality analysis.
AB  - Pollution haven hypothesis (PHH), which is defined as foreign direct investment
      inducing a raising impact on the pollution level in the hosting country, is
      lately a subject of discussion in the field of economics. This study, within the
      scope of related discussion, aims to look into the potential impact of foreign
      direct investments on CO2 emission in Turkey in 1974-2013 period using
      environmental Kuznets curve (EKC) model. For this purpose, Maki (Econ Model
      29(5):2011-2015, 2012) structural break cointegration test, Stock and Watson
      (Econometrica 61:783-820, 1993) dynamic ordinary least square estimator (DOLS),
      and Hacker and Hatemi-J (J Econ Stud 39(2):144-160, 2012) bootstrap test for
      causality method are used. Research results indicate the existence of a long-term
      balance relationship between FDI, economic growth, energy usage, and CO2
      emission. As per this relationship, in Turkey, (1) the potential impact of FDI on
      CO2 emission is positive. This result shows that PHH is valid in Turkey. (2)
      Moreover, this is not a one-way relationship; the changes in CO2 emission also
      affect FDI entries. (3) The results also provide evidence for the existence of
      the EKC hypothesis in Turkey. Within the frame of related findings, the study
      concludes several polities and presents various suggestions.

PMID- 29063406
TI  - Assessing watercourse quality: challenges in implementing European and Swiss
      legal frameworks.
AB  - Hydro-climatic changes and the increasing release of pollutants into rivers by
      human activities tend to affect the quality of watercourses, to alter aquatic
      ecosystems and to reduce the amount of useable water. The ecological and chemical
      states of rivers and their evolution is thus of growing concern. In Europe and
      Switzerland, water policies are progressively shifting towards a holistic
      approach of river systems. The European Commission notably established a
      framework to highlight rivers' ecological deficits and to enhance regional or
      local water management plans. In Switzerland, a similar framework is currently
      under development. In this paper, both procedures are compared and implemented in
      a Swiss catchment dominated by agricultural activities. The aim is to define the
      challenges that still need to be addressed to assess and sustain river health.
      The hydromorphological, ecological, and ecotoxicological quality of the river was
      evaluated. Both frameworks highlighted the fact that no section of the river can
      currently be classified as being in a good environmental state and that the state
      deteriorates as tributaries and wastewater discharge flow into the main riverbed.
      Chemical issues and water quality changes due to hydro-climatic variations and
      management strategies were also pinpointed. Both frameworks are thus useful tools
      to survey changes in rivers quality in space and over time. However, challenges
      remain regarding the appropriate strategies to monitor and analyze chemicals, the
      definition of target values and conditions, the evaluation and integration of
      human-induced pressures, and the overall evaluation of the state of a river. The
      development of integrated indicators or of ecosystem services approaches is
      considered as a potential solution to explore river health and to define
      efficient restoration measures by water managers.

PMID- 29063407
TI  - Heavy metal and nutrient uptake in plants colonizing post-flotation copper
      tailings.
AB  - Copper ore mining and processing release hazardous post-flotation wastes that are
      difficult for remediation. The studied tailings were extremely rich in Cu (1800
      mg kg-1) and contaminated with Co and Mn, and contained very little available
      forms of P, Fe, and Zn. The plants growing in tailings were distinctly enriched
      in Cu, Cd, Co, Ni, and Pb, and the concentration of copper achived the critical
      toxicity level in shoots of Cerastium arvense and Polygonum aviculare. The
      redundancy analysis demonstrated significant relationship between the
      concentration of available forms of studied elements in substrate and the
      chemical composition of plant shoots. Results of the principal component analysis
      enabled to distinguish groups of plants which significantly differed in the
      pattern of element accumulation. The grass species Agrostis stolonifera and
      Calamagrostis epigejos growing in the tailings accumulated significantly lower
      amounts of Cu, but they also had the lowest levels of P, Fe, and Zn in comparison
      to dicotyledonous. A. stolonifera occurred to be the most suitable species for
      phytostabilization of the tailings with regard to its low shoot Cu content and
      more efficient acquisition of limiting nutrients in relation to C. epigejos. The
      amendments improving texture, phosphorus fertilization, and the introduction of
      native leguminous species were recommended for application in the
      phytoremediation process of the tailings.

PMID- 29063408
TI  - 210Po and 210Pb bioaccumulation and possible related dose assessment in parasol
      mushroom (Macrolepiota procera).
AB  - Presented are results of a study on accumulation and distribution of 210Po and
      210Pb in the fruitbodies of parasol mushroom (Macrolepiota procera) and risk to
      human consumer due to exposure from highly radiotoxic decay particles emitted by
      both radionuclides. Mushrooms were collected from 16 forested places in central
      and northern regions of Poland. Activity concentrations of 210Po and 210Pb were
      determined after radiochemical separation of nuclides and subsequent measurement
      using validated method and alpha spectrometer. Results showed on spatially
      heterogeneous distribution of the 210Po and 210Po activity concentrations in M.
      procera and two interpolation maps were prepared. Activity concentrations of
      nuclides in dried caps of M. procera were in the range from 3.38 +/- 0.41 to
      16.70 +/- 0.33 Bq?210Po ?kg-1 and from 5.11 +/- 0.21 to 13.42 +/- 0.30 Bq?210Pb
      ?kg-1. Consumption of M. procera foraged in central and northern Poland should
      not contribute significantly to the annual effective radiation doses from 210Po
      and 210Pb due to amount of both nuclides accumulated by fungus in caps.

PMID- 29063409
TI  - Environmental impact assessment of municipal solid waste management options using
      life cycle assessment: a case study.
AB  - The goal of this study is to use life cycle assessment (LCA) tool to assess
      possible environmental impacts of different municipal solid waste management
      (MSWM) scenarios on various impact categories for the study area Dhanbad City,
      India. The scenarios included in the present study are collection and
      transportation (denoted as S1); baseline scenario consisting of recycling, open
      burning, open dumping, and finally unsanitary landfilling without energy recovery
      (denoted by S2); composting and landfilling (denoted by S3); and recycling and
      composting followed by landfilling of inert waste without energy recovery
      (denoted by S4). One ton of municipal solid waste (MSW) was selected as the
      functional unit. The primary data were collected through sampling, surveys, and
      literatures. Background data were obtained from Eco-invent data of SimaPro 8.1
      libraries. The scenarios were compared using the CML 2 baseline 2000 method, and
      the results indicated that the scenario S1 had the highest impact on marine
      aquatic ecotoxicity (1.86E + 04 kg 1,4-DB eq.) and abiotic depletion (2.09E + 02
      kg Sb eq.). S2 had the highest impact on global warming potential (9.42E + 03 kg
      CO2 eq.), acidification (1.15E + 01 kg SO2 eq.), eutrophication (2.63E + 00 kg
      PO43- eq.), photochemical oxidation (2.12E + 00 kg C2H4 eq.), and human toxicity
      (2.25E + 01 kg 1,4-DB eq.). However, S3 had the highest impact on abiotic
      depletion (fossil fuels) (2.71E + 02 MJ), fresh water aquatic ecotoxicity (6.54E
      + 00 kg 1,4-DB eq.), terrestrial ecotoxicity (3.36E - 02 kg 1,4-DB eq.), and
      ozone layer depletion (2.73E - 06 kg CFC-11 eq.). But S4 did not have the highest
      impact on any of the environmental impact categories due to recycling of
      packaging waste and landfilling of inert waste. Landfilling without energy
      recovery of mixed solid waste was found as the worst disposal alternative. The
      scenario S4 was found as the most environmentally suitable technology for the
      study area and recommended that S4 should be considered for strategic planning of
      MSWM for the study area.

PMID- 29063410
TI  - Discovery of Potent Neuraminidase Inhibitors Using a Combination of Pharmacophore
      Based Virtual Screening and Molecular Simulation Approach.
AB  - Neuraminidase (NA), a surface protein, facilitates the release of nascent virus
      and thus spreads infection. It has been renowned as a potential drug target for
      influenza A virus infection. The drugs such as oseltamivir, zanamivir, peramivir,
      and laninamivir are approved for the treatment of influenza infection.
      Additionally, investigational drugs namely MK2206, tamiphosphor, crenatoside, and
      dehydroepiandrosterone (DHEA) are also available for the treatment. However,
      recent outbreaks of highly pathogenic and drug-resistant influenza A strains
      highlighted the need to discover novel NA inhibitor. Keeping this in mind, in the
      current investigation, an effort was made to ascertain potent inhibitors using
      pharmacophore-based virtual screening and docking approach. A 3D pharmacophore
      model was generated based on the chemical features of approved and
      investigational NA inhibitors using PHASE module of Schrodinger suite. The model
      consists of two hydrogen bond acceptors (A), one hydrogen bond donor (D), and one
      positively charged group (P), AADP. Subsequently, molecules with same
      pharmacophoric features were screened from among the two million compounds
      available in the ZINC database using the generated pharmacophore hypothesis.
      Ligand filtration was also done to obtain an efficient collection of hit
      molecules by employing Lipinski "rule of five" using Qikprop module. Finally, the
      screened molecule was subjected to docking and molecular dynamic simulations to
      examine the inhibiting activity of the compounds. The results of our analysis
      suggest that "acebutolol hydrochloride" (156792) could be the promising
      candidates for the treatment of influenza A virus infection.

PMID- 29063411
TI  - Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation
      Strategies.
AB  - Sensitive and specific methodology is required for the detection and
      characterization of anti-drug antibodies (ADAs). High-quality ADA data enables
      the evaluation of potential impact of ADAs on the drug pharmacokinetic profile,
      patient safety, and efficacious response to the drug. Immunogenicity assessments
      are typically initiated at early stages in preclinical studies and continue
      throughout the drug development program. One of the potential bioanalytical
      challenges encountered with ADA testing is the need to identify and mitigate the
      interference mediated by the presence of soluble drug target. A drug target, when
      present at sufficiently high circulating concentrations, can potentially
      interfere with the performance of ADA and neutralizing antibody (NAb) assays,
      leading to either false-positive or, in some cases, false-negative ADA and NAb
      assay results. This publication describes various mechanisms of assay
      interference by soluble drug target, as well as strategies to recognize and
      mitigate such target interference. Pertinent examples are presented to illustrate
      the impact of target interference on ADA and NAb assays as well as several
      mitigation strategies, including the use of anti-target antibodies, soluble
      versions of the receptors, target-binding proteins, lectins, and solid-phase
      removal of targets. Furthermore, recommendations for detection and mitigation of
      such interference in different formats of ADA and NAb assays are provided.

PMID- 29063412
TI  - Epilepsy: Knowledge, Attitude, and Practice Among Secondary School Teachers in
      Khartoum State.
AB  - INTRODUCTION: Epilepsy is a continuing tendency to have seizures, i.e., a
      convulsion or any transient abnormal event resulting from paroxysmal cerebral
      neurons discharge, even if the attacks are separated by long intervals. Eighty
      nine percent of the global burden of epilepsy is in developing countries.
      Knowledge about the disease is the cornerstone for its treatment and prevention.
      OBJECTIVES: The aim of this study was to assess knowledge, attitude, and practice
      of secondary school teachers toward epilepsy in Khartoum state, Sudan. METHOD: A
      38-item structured close ended questionnaire was self-administered to 317
      secondary school teachers in Khartoum state, Sudan. RESULTS: The majority of the
      teachers knew about the term "epilepsy" (93.6%) and had witnessed an epileptic
      seizure (83.5%). But their knowledge about the etiology and treatment is
      generally poor: 48% believe that epileptic patients should not be treated
      normally in the community; 12.9% would tie and 47.6% would put a spoon in the
      mouth of the seizing patient. CONCLUSION: There is a relatively low level of
      knowledge, especially about treatment and whether the disease is curable or not.
      Also there is misconception about the etiology and treatment by traditional means
      in spite of the high educational level. There is a high level of negative
      attitude toward epileptic patients, especially in dealing with them as normal
      people who can live their lives, get married, and work in areas that suit them.
      There is a good level of positive practice toward epileptic seizures and their
      first aid measures, but there is also a high level of negative practice that can
      harm patients like tying them and putting a spoon in their mouths.

PMID- 29063413
TI  - Neighborhood Effects on PND Symptom Severity for Women Enrolled in a Home
      Visiting Program.
AB  - The aim of this study was to investigate the association between postnatal
      depression (PND) symptoms severity and structural neighborhood characteristics
      among women enrolled in a home visiting program. The sample included 295 mothers
      who were at risk for developing PND, observed as 3-month Edinburgh Postnatal
      Depression Scale (EPDS) scores >= 10. Two neighborhood predictor components
      (residential stability and social disadvantage) were analyzed as predictors of
      PND symptom severity using a generalized estimating equation. Residential
      stability was negatively associated with PND symptom severity. Social
      disadvantage was not found to be statistically significantly. The findings
      suggest that residential stability is associated with a reduction in PND symptom
      severity for women enrolled in home visiting program.

PMID- 29063414
TI  - Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts
      Consortium.
AB  - Several studies have reported a decline in incidence of dementia which may have
      large implications for the projected burden of disease, and provide important
      guidance to preventive efforts. However, reports are conflicting or inconclusive
      with regard to the impact of gender and education with underlying causes of a
      presumed declining trend remaining largely unidentified. The Alzheimer Cohorts
      Consortium aggregates data from nine international population-based cohorts to
      determine changes in the incidence of dementia since 1990. We will employ Poisson
      regression models to calculate incidence rates in each cohort and Cox
      proportional hazard regression to compare 5-year cumulative hazards across study
      specific epochs. Finally, we will meta-analyse changes per decade across cohorts,
      and repeat all analysis stratified by sex, education and APOE genotype. In all
      cohorts combined, there are data on almost 69,000 people at risk of dementia with
      the range of follow-up years between 2 and 27. The average age at baseline is
      similar across cohorts ranging between 72 and 77. Uniting a wide range of disease
      specific and methodological expertise in research teams, the first analyses
      within the Alzheimer Cohorts Consortium are underway to tackle outstanding
      challenges in the assessment of time-trends in dementia occurrence.

PMID- 29063416
TI  - Nonalcoholic Fatty Liver Disease Is Associated with Increased Risk of Reflux
      Esophagitis.
AB  - BACKGROUND: Reflux esophagitis is associated with obesity and metabolic syndrome;
      however, the relationship between nonalcoholic fatty liver disease (NAFLD) and
      reflux esophagitis is unclear. AIM: We examined the association between NAFLD and
      the development of reflux esophagitis. METHODS: Our cohort consisted of 117,377
      Korean adults without reflux esophagitis at baseline who underwent a health
      checkup program including upper endoscopy between 2002 and 2014 and were followed
      annually or biennially until December 2014. NAFLD was defined as hepatic
      steatosis on ultrasonography in the absence of excessive alcohol use or any other
      identifiable cause. RESULTS: Over 520,843.2 person-years of follow-up, 22,500
      participants developed reflux esophagitis (incidence density, 43.2 per 1000
      person-years). In models adjusted for age and sex, the adjusted hazard ratio
      (aHR) (95% confidence interval [CI]) for incident reflux esophagitis in subjects
      with NAFLD compared to those without was 1.16 (1.13-1.20). After further
      adjustment for confounders of center, year of visit, smoking status, alcohol
      intake, regular exercise, education level, and body mass index, the association
      between NAFLD and incident reflux esophagitis was attenuated, but remained
      significant (aHR 1.06; 95% CI 1.02-1.10). CONCLUSIONS: In this large cohort of
      Korean men and women, participants with NAFLD exhibited increased incidence of
      reflux esophagitis independent of possible confounders, suggesting that NAFLD
      contributes to the development of reflux esophagitis.

PMID- 29063415
TI  - Sex-Specific Neurotoxic Effects of Organophosphate Pesticides Across the Life
      Course.
AB  - PURPOSE OF REVIEW: This review discusses the sex-specific effects of exposure to
      various organophosphate (OP) pesticides throughout the life course and potential
      reasons for the differential vulnerabilities observed across sexes. RECENT
      FINDINGS: Sex is a crucial factor in the response to toxicants, yet the sex
      specific effects of OP exposure, particularly in juveniles and adults, remain
      unresolved. This is largely due to study design and inconsistencies in exposure
      and outcome assessments. Exposure to OPs results in multiple adverse outcomes
      influenced by many factors including sex. Reported sex-specific effects suggest
      that males are more susceptible to OPs, which reflects the sex-dependent
      prevalence of various neurodevelopmental and neurodegenerative disorders such as
      autism and amyotrophic lateral sclerosis (ALS), in which males are at greater
      risk. Thus, this review proposes that the biological sex-specific effects
      elicited by OP exposure may in part underlie the dimorphic susceptibilities
      observed in neurological disorders. Understanding the immediate and long-term
      effects of OP exposure across sexes will be critical in advancing our
      understanding of OP-induced neurotoxicity and disease.

PMID- 29063417
TI  - Propofol Does Not Reduce Pyroptosis of Enterocytes and Intestinal Epithelial
      Injury After Lipopolysaccharide Challenge.
AB  - BACKGROUND: To date, mechanisms of sepsis-induced intestinal epithelial injury
      are not well known. P2X7 receptor (P2X7R) regulates pyroptosis of lymphocytes,
      and propofol is usually used for sedation in septic patients. AIMS: We aimed to
      determine the occurrence of enterocyte pyroptosis mediated by P2X7R and to
      explore the effects of propofol on pyroptosis and intestinal epithelial injury
      after lipopolysaccharide (LPS) challenge. METHODS: A novel regimen of LPS
      challenge was applied in vitro and in vivo. Inhibitors of P2X7R (A438079) and
      NLRP3 inflammasome (MCC950), and different doses of propofol were administered.
      The caspase-1 expression, caspase-3 expression, caspase-11 expression, P2X7R
      expression and NLRP3 expression, extracellular ATP concentration and YO-PRO-1
      uptake, and cytotoxicity and HMGB1 concentration were detected to evaluate
      enterocyte pyroptosis in cultured cells and intestinal epithelial tissues. Chiu's
      score, diamine oxidase and villus length were used to evaluate intestinal
      epithelial injury. Moreover, survival analysis was performed. RESULTS: LPS
      challenge activated caspase-11 expression and P2X7R expression, enhanced ATP
      concentration and YO-PRO-1 uptake, and led to increased cytotoxicity and HMGB1
      concentration. Subsequently, LPS resulted in intestinal epithelial damage, as
      evidenced by increased levels of Chiu's score and diamine oxidase, and shorter
      villus length and high mortality of animals. A438079, but not MCC950,
      significantly relieved LPS-induced enterocyte pyroptosis and intestinal
      epithelial injury. Importantly, propofol did not confer the protective effects on
      enterocyte pyroptosis and intestinal epithelia although it markedly decreased
      P2X7R expression. CONCLUSION: LPS attack leads to activation of caspase-11/P2X7R
      and pyroptosis of enterocytes. Propofol does not reduce LPS-induced pyroptosis
      and intestinal epithelial injury, although it inhibits P2X7R upregulation.

PMID- 29063420
TI  - Correction to: Altered oscillation of Doppler-derived renal and renal interlobar
      venous flow velocities in hypertensive and diabetic patients.
AB  - In the original publication of this paper the legend of Fig. 1 should read as:
      Fig. 1 Pulsed Doppler flow velocity recordings of the aorta (a), right renal
      artery (b), right renal interlobar artery (c), inferior vena cava (d), right
      renal vein (e), and right renal interlobar vein (f). PSV peak systolic velocity,
      EDV end-diastolic velocity, V MAX maximum velocity, V MIN minimum velocity.

PMID- 29063419
TI  - Understanding Cultural Influences on Dietary Habits in Asian, Middle Eastern, and
      Latino Patients with Type 2 Diabetes: A Review of Current Literature and Future
      Directions.
AB  - PURPOSE OF REVIEW: This review focuses on evaluating and identifying gaps in the
      current literature regarding culturally specific dietary influences for patients
      with type 2 diabetes. As this topic has previously been examined in African
      American populations, we chose to focus on four other distinct populations
      (Hispanic, Middle Eastern, Western Pacific, South Asian). Given the rapid
      increase in global rates of type 2 diabetes and high rates of diabetes among
      certain ethnic groups, it is important to understand how culturally adapted
      strategies in diabetes management have been described in different regions and
      populations. RECENT FINDINGS: The specific role of nutrition in controlling
      diabetes is tied to cultural habits and customs. Variation in cultural practices,
      including diet, create unique environments in which patients with diabetes must
      navigate. The role of family, particularly among Hispanics, is crucial to
      cultural adaptations of diabetes management. Incorporating alternative medicine,
      namely observed in Chinese and Indian populations, also guided diabetes care
      strategies. Language barriers, health literacy, and acculturation were all unique
      factors affecting cultural approaches to diabetes management in these four
      populations. Understanding such cultural determinants is crucial to addressing
      diabetes disparities and improving outcomes.

PMID- 29063422
TI  - Anisotropic dehydration of hydrogel surfaces.
AB  - Efforts to develop tissue-engineered skin for regenerative medicine have explored
      natural, synthetic, and hybrid hydrogels. The creation of a bilayer material,
      with the stratification exhibited by native skin, is a complex problem. The
      mechanically robust, waterproof epidermis presents the stratum corneum at the
      tissue/air interface, which confers many of these protective properties. In this
      work, we explore the effect of high temperatures on alginate hydrogels, which are
      widely employed for tissue engineering due to their excellent mechanical
      properties and cellular compatibility. In particular, we investigate the rapid
      dehydration of the hydrogel surface which occurs following local exposure to
      heated surfaces with temperatures in the range 100-200  degrees C. We report the
      creation of a mechanically strengthened hydrogel surface, with improved puncture
      resistance and increased coefficient of friction, compared to an unheated
      surface. The use of a mechanical restraint during heating promoted differences in
      the rate of mass loss; the rate of temperature increase within the hydrogel, in
      the presence and absence of restraint, is simulated and discussed. It is hoped
      that the results will be of use in the development of processes suitable for
      preparing skin-like analogues; application areas could include wound healing and
      skin restoration.

PMID- 29063418
TI  - Health Benefits of Fasting and Caloric Restriction.
AB  - PURPOSE OF REVIEW: Obesity and obesity-related diseases, largely resulting from
      urbanization and behavioral changes, are now of global importance. Energy
      restriction, though, is associated with health improvements and increased
      longevity. We review some important mechanisms related to calorie limitation
      aimed at controlling of metabolic diseases, particularly diabetes. RECENT
      FINDINGS: Calorie restriction triggers a complex series of intricate events,
      including activation of cellular stress response elements, improved autophagy,
      modification of apoptosis, and alteration in hormonal balance. Intermittent
      fasting is not only more acceptable to patients, but it also prevents some of the
      adverse effects of chronic calorie restriction, especially malnutrition. There
      are many somatic and potentially psychologic benefits of fasting or intermittent
      calorie restriction. However, some behavioral modifications related to abstinence
      of binge eating following a fasting period are crucial in maintaining the desired
      favorable outcomes.

PMID- 29063423
TI  - Examining the response programming function of the Quiet Eye: Do tougher shots
      need a quieter eye?
AB  - Support for the proposition that the Quiet Eye (QE) duration reflects a period of
      response programming (including task parameterisation) has come from research
      showing that an increase in task difficulty is associated with increases in QE
      duration. Here, we build on previous research by manipulating three elements of
      task difficulty that correspond with different parameters of golf-putting
      performance; force production, impact quality and target line. Longer QE
      durations were found for more complex iterations of the task and furthermore,
      more sensitive analyses of the QE duration suggest that the early QE proportion
      (prior to movement initiation) is closely related to force production and impact
      quality. However, these increases in QE do not seem functional in terms of
      supporting improved performance. Further research is needed to explore QE's
      relationship with performance under conditions of increased difficulty.

PMID- 29063424
TI  - Assessing renal changes after remote ischemic preconditioning (RIPC) of the upper
      extremity using BOLD imaging at 3T.
AB  - OBJECTIVE: Acute kidney injury (AKI) is an important risk factor for a number of
      adverse outcomes including end-stage renal disease and cardiovascular morbidity
      and mortality. Whilst many clinical situations that can induce AKI are known-e.g.
      drug toxicity, contrast agent exposure or ischemia during surgery-targeted
      preventive or therapeutic measures are still lacking. As to renoprotective
      strategies, remote ischemic preconditioning (RIPC) is one of the most promising
      novel approaches and has been examined by a number of clinical trials. The aim of
      this study was to use blood oxygenation level-dependent (BOLD) MRI as a surrogate
      parameter to assess the effect of RIPC in healthy volunteers. MATERIALS AND
      METHODS: In this IRB-approved, prospective study, 40 healthy volunteers were
      stratified with 20 undergoing an RIPC procedure (i.e. RIPC group) with a
      transient ischemia of the right arm, and 20 undergoing a sham procedure. Before
      and after the procedure, both kidneys of all participants were scanned using a 12
      echo mGRE sequence for functional BOLD imaging at 3T. For each volunteer, 180
      ROIs were placed in the cortex and the medulla of the kidneys. Ultimately, R2*
      values, which have an inverse correlation with the oxygenation level of tissue,
      were averaged for the RIPC and control groups. RESULTS: Following intervention,
      mean R2* values significantly decreased in the RIPC group in both the cortex
      (18.6 +/- 2.3 vs. 17.5 +/- 1.7 Hz; p = 0.0047) and medulla (34 +/- 5.2 vs. 32.2
      +/- 4.2 Hz; p = 0.0001). However, no significant differences were observed in the
      control group. CONCLUSION: RIPC can be non-invasively assessed in healthy
      volunteers using BOLD MRI at 3T, demonstrating a higher oxygen content in kidney
      tissue. This study presents a first-in-man trial establishing a quantifiable
      readout of RIPC and its effects on kidney physiology. BOLD measurements may
      advance clinical trials in further evaluating RIPC for future clinical care.

PMID- 29063425
TI  - Correction to: A phase I/II study of gemcitabine during radiotherapy in children
      with newly diagnosed diffuse intrinsic pontine glioma.
AB  - In Table 2 of the original publication, there were errors in the baseline scores
      for the PedsQL TM 3.0 Cancer Module questionnaire, so a corrected version of
      Table 2 is shown in this erratum. In the subcategories of the PedsQL TM 3.0
      Cancer Module questionnaire, nausea and fear of procedure did not score
      significantly lower after treatment compared to baseline. So, based on the
      corrected data in Table 2, there was no significant decrease in the total score
      of the cancer questionnaire, and this statement in the previous manuscript was
      incorrect.

PMID- 29063426
TI  - Introduction.
AB  - Atopic dermatitis (AD) is a chronic relapsing condition that is characterized by
      itching and redness of the skin. Our modern usage of atopic dermatitis dates back
      to 1933, when Wise and Sulzberger first coined the term to signify the disease's
      close association with other respiratory atopy, such as bronchial asthma and
      allergic rhinitis. A recent systematic review of 69 cross-sectional and cohort
      studies has confirmed that AD is now a worldwide phenomenon with lifetime AD
      prevalences of well over 20% in many affluent country settings. Although there is
      no obvious consistent overall global trend in the prevalence of AD, studies have
      shown that climate, urbanization, lifestyle, and socioeconomic class influence
      the prevalence of atopic dermatitis. Despite the pervasiveness of the disease, an
      understanding of atopic dermatitis has been hampered by a number of factors. Data
      suggests that extrinsic environmental factors work in concert with intrinsic
      immune mechanism and genetic factors to drive disease progression. With such a
      complex etiology, management of atopic dermatitis currently at best achieves
      symptomatic control rather than cure. This approach poses a significant burden on
      healthcare resources, as well as patients' quality of life. Current management
      methods of AD often involves a combination of non-pharmacologic modalities and
      prescription medications. Though they can be effective when employed, there are
      significant barriers to treatment for patients including time, costs, and
      medication side effects. Our aim, throughout this text, is to explore the
      complexities of AD, providing the healthcare provider with tips and tricks to
      improve patient care and satisfaction and the most current trends and treatment
      approaches on the horizon.

PMID- 29063427
TI  - Atopic Dermatitis: Disease Background and Risk Factors.
AB  - Multiple risk factors have been associated with the development of atopic
      dermatitis (AD). Recent advances in understanding the role of genetics in this
      disease have been made, with discovery of the filaggrin (FLG) gene as the most
      notable so far. In addition to FLG gene mutations as a risk factor for AD, a
      positive family history of atopic or allergic disease in either parent, has been
      shown to confer a greater risk of developing AD. Atopic dermatitis usually
      presents early in life and is thought to represent the initial-step in the
      "atopic march" which is characterized by the development of other atopic diseases
      later in life such as asthma, allergic rhinitis and/or rhinoconjunctivitis, food
      allergies and hay fever. Other comorbid diseases that have been associated with
      AD include increase risk of viral and bacterial skin infections, neuropsychiatric
      diseases such as attention-deficit hyperactivity disorders (ADHD) and autistic
      spectrum disorder (ASD). Patients with AD, have also been found to have worse
      sleep quality overall compared to patients without AD. In this chapter, we will
      discuss the risk factors associated with development of atopic dermatitis as well
      as the most commonly reported comorbidities in patients with this disease.

PMID- 29063428
TI  - Atopic Dermatitis: Pathophysiology.
AB  - The pathophysiology of atopic dermatitis is complex and multifactorial, involving
      elements of barrier dysfunction, alterations in cell mediated immune responses,
      IgE mediated hypersensitivity, and environmental factors. Loss of function
      mutations in filaggrin have been implicated in severe atopic dermatitis due to a
      potential increase in trans-epidermal water loss, pH alterations, and
      dehydration. Other genetic changes have also been identified which may alter the
      skin's barrier function, resulting in an atopic dermatitis phenotype. The
      imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create
      alterations in the cell mediated immune responses and can promote IgE mediated
      hypersensitivity, both of which appear to play a role in the development of
      atopic dermatitis. One must additionally take into consideration the role of the
      environment on the causation of atopic dermatitis and the impact of chemicals
      such as airborne formaldehyde, harsh detergents, fragrances, and preservatives.
      Use of harsh alkaline detergents in skin care products may also unfavorably alter
      the skin's pH causing downstream changes in enzyme activity and triggering
      inflammation. Environmental pollutants can trigger responses from both the innate
      and adaptive immune pathways. This chapter will discuss the multifaceted etiology
      of atopic dermatitis which will help us to elucidate potential therapeutic
      targets. We will also review existing treatment options and their interaction
      with the complex inflammatory and molecular triggers of atopic dermatitis.

PMID- 29063429
TI  - Clinical Presentation of Atopic Dermatitis.
AB  - Atopic dermatitis, commonly known as eczema, is a chronic inflammatory dermatosis
      that can affect individuals from infancy to adulthood. Also referred to as "the
      itch that rashes", atopic dermatitis is classically associated with significant
      pruritus that is accompanied by characteristic cutaneous and other clinical
      findings. The diagnosis of atopic dermatitis can be challenging due to the wide
      range of clinical presentations based on patient factors such as age, skin type,
      ethnicity, and other comorbid conditions. This chapter reviews the classical
      findings as well as the less common manifestations of atopic dermatitis.

PMID- 29063430
TI  - Atopic Dermatitis Disease Complications.
AB  - This chapter will describe infectious complications of atopic dermatitis,
      including bacterial, viral, and fungal infections and the evolving understanding
      of the relationship between atopic dermatitis and infectious disease. The
      underlying immunological dysregulation and poor skin barrier function associated
      with atopic dermatitis not only increases the likelihood of infectious
      complications, but also lends atopic dermatitis skin vulnerable to flares induced
      by environmental triggers. Thus, this chapter will also highlight the impact of
      common external environmental agents on precipitating flares of disease. Lastly,
      this chapter will discuss complications that can arise from treatments and the
      association of atopic dermatitis with more serious conditions such as lymphoma.

PMID- 29063431
TI  - The Psychosocial Impact of Atopic Dermatitis.
AB  - Atopic dermatitis is a chronic skin condition which has significant psychosocial
      and quality of life impact. The condition causes physical discomfort, emotional
      distress, embarrassment, social stigma and daily activity limitation. In an
      effort to assess these aspects of disease burden, quality of life measurement
      tools were developed. Through use of these tools, we have expanded our knowledge
      of the psychosocial and quality of life burden of this condition. A variety of
      quality of life assessment tools exist, yet there is no consensus on which tool
      is best suited to assess the quality of life impact of atopic dermatitis.
      Research studies assessing quality of life in atopic dermatitis patients utilize
      a variety of quality of life measurement tools; this complicates comparisons
      across research studies. Though comparison across studies is difficult, the data
      echoes tremendous overall burden of disease, especially pertaining to
      psychosocial status and life quality.

PMID- 29063432
TI  - Stressors in Atopic Dermatitis.
AB  - As with other inflammatory skin disorders, atopic dermatitis has a tendency to
      cause stress and also be exacerbated by it. Patients with atopic dermatitis have
      several disease-associated stressors, some of which include physical discomfort
      due to itching and altered appearance due to flare-ups. These stressors have been
      shown to effect patients psychosocially by altering sleep patterns, decreasing
      self-esteem and interfering with interpersonal relationships. In combination with
      its direct effect on patients, atopic dermatitis also causes stress for parents
      and caregivers. Studies suggest that atopic dermatitis is strongly correlated
      with co-sleeping habits, which can negatively impact the health and mood of
      parents or caregivers. It has also been reported to interfere with the formation
      of a strong mother-child relationship. In order to optimize treatment for
      patients with atopic dermatitis, it is important to note the impact that it has
      on quality of life. By implementing patient counseling, sleep-targeted therapies,
      and the use of quality of life (QoL) indices, atopic dermatitis patients and
      caregivers have the potential to experience greater satisfaction with treatment.

PMID- 29063433
TI  - The Economics Burden of Atopic Dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory disorder that affects over 30
      million people in the United States of America. Given the large and growing
      prevalence of AD, the associated economic burden is significant. It has been
      estimated that AD costs over $5 billion dollars annually. These costs include
      both direct and indirect costs. Direct costs include prescription medicines,
      visits to health care providers, hospitalizations, and transportation. Indirect
      costs include missed days or lost productivity at work or school, career
      modification, and reduced quality of life. Understanding and measuring these
      costs can be accomplished through rigorous economic evaluation, which is the
      organized process of considering inputs and outcomes of various activities.
      Economic evaluation has been used to contextualize the burden of AD in society.
      It has also been used to inform patients, providers, and other stakeholders on
      how to deliver the most evidence-based, efficient care possible. Understanding
      the economic impact of atopic dermatitis is an important aspect of delivering
      high quality care.

PMID- 29063434
TI  - Defining and Measuring the Scope of Atopic Dermatitis.
AB  - Atopic dermatitis (AD) has no definitive diagnostic test and has a large range of
      phenotypes, making it a difficult disease to assess and define. However, an
      agreed-upon definition of AD is important for clinical trials, population-based
      studies, and clinical practice. Several diagnostic criteria systems have been
      proposed to fill these needs, with none considered the gold standard. To further
      aid in standardized assessment of AD patients, numerous disease severity and
      quality of life measurement tools have been proposed. There is similarly no gold
      standard and efforts are ongoing to develop a single consensus scale. Finally,
      assessment of AD-associated comorbidities, including allergic/immunologic
      conditions, psychiatric disorders, and metabolic/cardiac conditions, is important
      when evaluating this patient population.

PMID- 29063435
TI  - Prescription Treatment Options.
AB  - Atopic dermatitis frequently requires the use of over-the-counter and
      prescription medications for effective management. Emollients and topical
      corticosteroids are effective for most patients and are the most commonly
      utilized agents by experienced dermatologists. Antihistamines, antibiotics, and
      calcineurin inhibitors may also prove helpful in the correct clinical scenarios.
      Severe atopic dermatitis, however, can be difficult to manage and not
      infrequently require substantial immunomodulatory medications. Targeted molecular
      therapies, such as dupilumab, are promising, emerging atopic dermatitis
      therapies. The medication pearls reviewed in this chapter will assist providers
      in managing atopic dermatitis patients.

PMID- 29063436
TI  - Non-Prescription Treatment Options.
AB  - The pathogenesis of atopic dermatitis (AD) is complex and multifactorial.
      However, recent advancements in the genetics and pathophysiology of AD suggest
      that epidermal barrier dysfunction is paramount in the development and
      progression of the condition (Boguniewicz and Leung, Immunol Rev 242(1):233-246,
      2011). In addition to standard therapy for AD, there are a plethora of non
      prescription treatment modalities which may be employed. Over-the-counter
      treatments for atopic dermatitis can come in the form of topical corticosteroids,
      moisturizers/emollients, and oral anti-histamines. Though these treatments are
      beneficial, prescription treatments may be quicker acting and more efficacious in
      patients with moderate to severe disease or during flares. OTC agents are best
      used for maintenance between flares and to prevent progression of mild disease.
      Alternative and complementary treatments lack strong efficacy evidence. However,
      wet wraps, bleach baths, and other treatments appear to be promising when used in
      conjunction with conventional treatments. With the financial burden of atopic
      dermatitis ranging from 364 million to 3.8 billion dollars each year in the
      United States, we suspect this topic will gain further research attention.

PMID- 29063437
TI  - Adherence in Atopic Dermatitis.
AB  - Atopic dermatitis is a chronic dermatologic condition requiring extended
      treatment times with topical application of medications. While atopic dermatitis
      treatments can be highly effective when used as directed, oftentimes patients do
      not respond as expected, raising concern for non-adherence versus non-response.
      This chapter aims to describe what is currently known about adherence in atopic
      dermatitis and to discuss strategies to improve adherence in order to improve
      treatment outcomes. Whether intentional or unintentional, non-adherence to
      treatment can limit patient outcomes of this disease for a variety of reasons.
      These include frustration with medication efficacy, inconvenience, and fear of
      side effects. Other factors include forgetfulness, financial burden of treatment,
      lack of trust in the physician, dislike of prescribed medication, or lack of
      understanding of disease or treatment. Several interventions have been studied
      with the aim of improving adherence in atopic dermatitis-such as educational
      workshops for patients and caregivers, earlier follow-up visits, and text
      messages reminders-however these are often limited by sample size and power.
      Further research is needed to study both specific patterns of nonadherence in
      atopic dermatitis, as well as methods to improve them.

PMID- 29063438
TI  - Atopic Dermatitis: Managing the Itch.
AB  - Atopic dermatitis has a substantial impact on sleep, appearance, psychological
      well-being, and other qualities of life. The visual appearance of
      lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be
      socially stigmatizing, and treatment of these symptoms is challenging. In
      managing pruritus in patients, practitioners should assess and document pruritus
      through questionnaires at each routine visit. Initially, practitioners should
      advise patients to employ non-pharmaceutical treatments such as emollients with
      wet wraps, elimination of triggers, changing scratching habits, and psychological
      interventions. If these methods of treatment are not successful or if the disease
      presentation is severe, pharmacological therapies should be employed. This
      chapter describes the therapeutic ladder for pruritus in atopic dermatitis and
      discusses each treatment modality in further detail for practitioners to advise
      their patients.First-line topical pharmaceutical agents include topical
      glucocorticoids and topical calcineurin inhibitors. Second-line topical agents
      include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents
      has been exhausted, primary systemic agents can be applied. These include
      sedating antihistamines, non-sedating antihistamines, oral glucocorticoids, or
      cyclosporine A. Finally, neuromodulating or immunomodulating agents can be
      attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and
      opioid receptor modulators. Outside of pharmacological treatments, phototherapy
      has been shown to provide a dramatic improvement of pruritus in atopic dermatitis
      and can be used at any stage of treatment including as a first-line agent.

PMID- 29063439
TI  - Atopic Dermatitis Disease Education.
AB  - Atopic dermatitis is a skin condition that is increasing burdensome to patient's
      lives. Patients require effective strategies to cope with the condition as well
      as the vast amount of new research that is coming to the forefront. This chapter
      discusses the patient education aspect of atopic dermatitis. We drew from various
      sources-such as peer-reviewed academic journals, online groups, and
      organizational websites-to provide a brief survey of the available types of
      patient educational resources. We discuss educational materials and
      interventions, such as workshops and support groups. In addition to the content
      of the workshops, we also explore the importance of their facilitators. We also
      review organizations in the US that pertain to atopic dermatitis and eczema care,
      such as the National Eczema Association and the American Academy of Dermatology.
      Lastly, we survey the role of technology-such as social media, web-based
      applications and teledermatology-in facilitating patient education. Despite the
      promising impacts of these technological interventions in the way patients
      consume educational materials, we also acknowledge that they are not widely used.

PMID- 29063440
TI  - The Future of Atopic Dermatitis Treatment.
AB  - In recent years, there has been a growing movement towards the use of targeted
      therapies in treating of atopic dermatitis (AD), parallel to that which has
      occurred in psoriasis. Among the systemic medications being studied are
      subcutaneous or intravenously administered biologic drugs targeting specific
      molecules such as IL4, IL13, IL17, and IgE. Non-biologic oral therapies are also
      being developed for AD and include small molecule drugs targeting
      phosphodiesterase type IV (PDE4) inhibition or Janus Kinase (JAK) inhibition.
      Numerous topical formulations are also being studied, with some formulations that
      are novel therapies that act as topical biologic or small molecule agents with
      mechanisms of action similar to systemic treatments. Others are being developed
      as skin barrier repair therapies for reduction of AD symptoms. This chapter will
      discuss new advances in AD treatment from medications in the initial stages of
      development to those nearing FDA approval.

PMID- 29063442
TI  - Between Past and Present: The Sociopsychological Constructs of Colonialism,
      Coloniality and Postcolonialism.
AB  - If one of the major aspirations of postcolonial theory is to re-establish a
      balance in the relationship between the (former) colonizer and the colonized by
      engaging the voices of the "subaltern", and on the other hand to illuminate how
      power relations of the present are embedded in history (Mills 2007), we argue
      that important theoretical insights might inform research by anchoring post
      colonial theory within a sociopsychological framework. While there is a growing
      corpus of sociopsychological research articles focusing on how major geopolitical
      events and historical processes bear on people's lives, we aim to investigate the
      theoretical potential of postcolonial theory within the disciplines aiming at a
      sociopsychological approach. By focusing on the social dynamics of power
      imbalances, post-colonial theory finds its operational meaning: the feelings
      stemming from actions committed in the past are indeed crucial in determining
      reparatory attitudes and policies towards members of former colonized groups.
      Firstly, drawing from the sociopsychological scientific production related to
      consequences of colonial past, seen in recent years as a growing research
      interest in the field, we will explore patterns and trends through a thematic
      analysis of literature. Social Psychology as well as adjacent disciplines can
      greatly benefit from this theoretical fertilization, especially in the way post
      colonial ideologies relate to the symbolic promotion versus exclusion of
      indigenous culture (Sengupta et al., International Journal of Intercultural
      Relations, 36(4), 506-517, 2012). Furthermore, by comparing and contrasting the
      ideological cosmologies relating to this particular topic, this study aims to
      establish the state of knowledge in the field, to identify how research methods
      and thematic fields are paired, to find "gaps" and create spaces for research
      that become integrative of postcolonial theory. While focusing on academic
      production, we also hope to contribute to develop the idea of cosmopolitism
      within academia but also beyond academic doors.

PMID- 29063441
TI  - Building Blocks of Psychology: on Remaking the Unkept Promises of Early Schools.
AB  - The appeal and popularity of "building blocks", i.e., simple and dissociable
      elements of behavior and experience, persists in psychological research. We begin
      our assessment of this research strategy with an historical review of
      structuralism (as espoused by E. B. Titchener) and behaviorism (espoused by J. B.
      Watson and B. F. Skinner), two movements that held the assumption in their
      attempts to provide a systematic and unified discipline. We point out the ways in
      which the elementism of the two schools selected, framed, and excluded topics of
      study. After the historical review, we turn to contemporary literature and
      highlight the persistence of research into building blocks and the associated
      framing and exclusions in psychological research. The assumption that complex
      categories of human psychology can be understood in terms of their elementary
      components and simplest forms seems indefensible. In specific cases, therefore,
      reliance on the assumption requires justification. Finally, we review alternative
      strategies that bypass the commitment to building blocks.

PMID- 29063443
TI  - Beyond Verbal Narratives: Using Timeline Images in the Semiotic Cultural Study of
      Meaning Making.
AB  - Contemporary semiotic cultural tradition in psychology views human meaning making
      as unfolding through the negotiation of multiple real and imagined scenarios and
      storylines. While emphasising this complex and layered nature of meaning making,
      this research tradition offers little methodological guidance for appreciating
      and evidencing this multiplicity in data analysis and interpretation. This paper
      suggests that a methodological approach that combines visual and verbal ways of
      representing one's personal stories might offer a useful alternative for
      evidencing the multiple meanings that individuals create about their personal
      journeys. By presenting two examples of drawn timeline images and corresponding
      interview extracts, the paper discusses how the chosen methodological approach
      offered opportunities for participants to 'show and tell' their complex and
      layered stories, and gave them freedom and agency to shape the research encounter
      and data production processes. The paper also highlights how the incorporation of
      visual methods into the methodology enabled the researcher to find alternative
      ways of interpreting participants' stories. The paper argues for a purposeful
      integration of visual and verbal methods, where the semiotic tensions and clashes
      between these modes can reveal novel ways of seeing researchers' and
      participants' meanings in the making.

PMID- 29063444
TI  - Fast Inactivation of CaV2.2 Channels Is Prevented by the Gbeta1 Subunit in Rat
      Sympathetic Neurons.
AB  - Voltage-dependent regulation of CaV2.2 channels by G-proteins is performed by the
      beta (Gbeta) subunit. Most studies of regulation by G-proteins have focused on
      channel activation; however, little is known regarding channel inactivation. This
      study investigated inactivation of CaV2.2 channels in superior cervical ganglion
      neurons that overexpressed Gbeta subunits. CaV2.2 currents were recorded by whole
      cell patch clamping configuration. We found that the Gbeta1 subunit reduced
      inactivation, while Gbeta5 subunit did not alter at all inactivation kinetics
      compared to control recordings. CaV2.2 current decay in control neurons consisted
      of both fast and slow inactivation; however, Gbeta1-overexpressing neurons
      displayed only the slow inactivation. Fast inactivation was restored by a strong
      depolarization of Gbeta1-overexpressing neurons, therefore, through a voltage
      dependent mechanism. The Gbeta1 subunit shifted the voltage dependence of
      inactivation to more positive voltages and reduced the fraction of CaV2.2
      channels resting in the inactivated state. These results support that the Gbeta1
      subunit inhibits the fast inactivation of CaV2.2 channels in SCG neurons. They
      explain the long-observed sustained Ca2+ current under G-protein modulation.

PMID- 29063445
TI  - IL-17 Exerts Anti-Apoptotic Effect via miR-155-5p Downregulation in Experimental
      Autoimmune Encephalomyelitis.
AB  - Multiple sclerosis is an autoimmune, neurodegenerative disease, affecting mostly
      young adults and resulting in progressive disability. It is a multifactorial
      disorder, with important involvement of both cellular and epigenetic components.
      Among the epigenetic factors, microRNAs are currently intensively investigated in
      the context of multiple sclerosis. It has been shown that their biogenesis and
      function may be regulated by various cytokines. IL-17, a hallmark cytokine of
      Th17 cells, has been thought to function predominantly as a pro-inflammatory
      factor, leading to increased disease symptoms. However, there are several studies
      indicating its protective role during inflammatory process. In this work, we have
      assessed the impact of high-dose IL-17 administration on microRNAs' expression
      profile during the preclinical stage of EAE. For selected microRNA, we have
      performed computational analysis of its potential target mRNAs and cellular
      pathways. Based on results obtained from in silico analysis, we have chosen genes
      from neurotrophin signaling pathway for further experiments-BDNF, HRAS, and BCL2.
      Results obtained in this study suggested that high dose of IL-17 exerts
      protective activity via miR-155-5p downregulation. Increased expression of all
      studied genes, especially BCL2, indicated a potential anti-apoptotic function of
      IL-17 during the preclinical phase of EAE.

PMID- 29063447
TI  - Stage IV gastric cancer successfully treated by multidisciplinary therapy
      including chemotherapy, immunotherapy, and surgery: a case report.
AB  - BACKGROUND: The prognosis of stage IV gastric cancer (GC) still remains
      unfavorable. Multidisciplinary approaches should therefore be considered to
      improve the survival of patients with stage IV GC. We report here a case of
      primary GC with potentially unresectable metastasis, successfully treated by a
      multidisciplinary approach including chemotherapy, immunotherapy, and surgery.
      CASE PRESENTATION: A 74-year-old man presented with multiple left neck masses.
      Abdominal computed tomography showed a thickened gastric wall and multiple
      lymphadenopathies including left supraclavicular lymph node. Gastroenterological
      endoscopy revealed tumor lesions in the gastric cardia. Tumor biopsy indicated a
      pathological diagnosis of poorly differentiated adenocarcinoma. Open left
      cervical lymph node biopsy showed histological features identical with the
      gastric tumor, indicating left clavicle lymph node metastasis of GC. After 2
      years of chemo-immunotherapy with S-1/CDDP, paclitaxel, and cytokine-activated
      killer cells, lesions other than the stomach lesion had regressed to undetectable
      on imaging studies. The patient then underwent laparoscopy-assisted total
      gastrectomy with Roux-en-Y reconstruction followed by adjuvant chemo
      immunotherapy with paclitaxel and S-1 for 1 year, and immunotherapy with tumor
      lysate-pulsed dendritic cell-activated killer cells for 5 years. The patient
      remained well after 5 years and 6 months of follow-up, with no signs of
      recurrence. CONCLUSION: Therapeutic combinations including immunotherapy may thus
      allow surgery to be performed in patients previously considered unsuitable for
      surgical intervention, potentially leading to a clinical cure, as in the current
      case.

PMID- 29063446
TI  - Extensive colonization with carbapenemase-producing microorganisms in Romanian
      burn patients: infectious consequences from the Colectiv fire disaster.
AB  - Health care of severe burn patients is highly specialized and may require
      international patient transfer. Burn patients have an increased risk of
      developing infections. Patients that have been hospitalized in countries where
      carbapenemase-producing microorganisms (CPMO) are endemic may develop infections
      that are difficult to treat. In addition, there is a risk on outbreaks with CPMOs
      in burn centers. This study underlines that burn patients may extensively be
      colonized with CPMOs, and it provides best practice recommendations regarding
      clinical microbiology and infection control. We evaluated CPMO-carriage and wound
      colonization in a burn patient initially treated in Romania, and transported to
      the Netherlands. The sequence types and acquired beta-lactamase genes of highly
      resistant microorganisms were derived from next generation sequencing data. Next,
      we searched literature for reports on CPMOs in burn patients. Five different
      carbapenemase-producing isolates were cultured: two unrelated OXA-48-producing
      Klebsiella pneumoniae isolates, OXA-23-producing Acinetobacter baumanii, OXA-48
      producing Enterobacter cloacae, and NDM-1-producing Providencia stuartii. Also,
      multi-drug resistant Pseudomonas aeruginosa isolates were detected. Among the
      sampling sites, there was high variety in CPMOs. We found 46 reports on CPMOs in
      burn patients. We listed the epidemiology of CPMOs by country of initial
      treatment, and summarized recommendations for care of these patients based on
      these reports and our study.

PMID- 29063449
TI  - Thrombectomy in ischemic stroke due to metastatic sacral chordoma: a case report.

PMID- 29063448
TI  - Prenatal methamphetamine exposure is associated with corticostriatal white matter
      changes in neonates.
AB  - Diffusion tensor imaging (DTI) studies have shown that prenatal exposure to
      methamphetamine is associated with alterations in white matter microstructure,
      but to date no tractography studies have been performed in neonates. The striato
      thalamo-orbitofrontal circuit and its associated limbic-striatal areas, the
      primary circuit responsible for reinforcement, has been postulated to be
      dysfunctional in drug addiction. This study investigated potential white matter
      changes in the striatal-orbitofrontal circuit in neonates with prenatal
      methamphetamine exposure. Mothers were recruited antenatally and interviewed
      regarding methamphetamine use during pregnancy, and DTI sequences were acquired
      in the first postnatal month. Target regions of interest were manually
      delineated, white matter bundles connecting pairs of targets were determined
      using probabilistic tractography in AFNI-FATCAT, and fractional anisotropy (FA)
      and diffusion measures were determined in white matter connections. Regression
      analysis showed that increasing methamphetamine exposure was associated with
      reduced FA in several connections between the striatum and midbrain,
      orbitofrontal cortex, and associated limbic structures, following adjustment for
      potential confounding variables. Our results are consistent with previous
      findings in older children and extend them to show that these changes are already
      evident in neonates. The observed alterations are likely to play a role in the
      deficits in attention and inhibitory control frequently seen in children with
      prenatal methamphetamine exposure.

PMID- 29063450
TI  - The "heart appearance" sign on MRI of Wernekink's commissure syndrome caused by
      bilateral caudal paramedian midbrain infarction.

PMID- 29063451
TI  - Diabetic polyneuropathy, deep white matter lesions, and carotid atherosclerosis:
      is there any association?
AB  - The morphologic and functional damages of diabetes mellitus (DM) on
      microcirculation can play a role in the pathogenesis of both polyneuropathy and
      cerebral white matter lesions. The aim of this study is to investigate the
      relation between polyneuropathy and cerebral deep white matter lesions (DWMLs)
      and carotid atherosclerosis in patients with type 2 DM. Sixty-six patients with
      type 2 DM without any disorder that may cause polyneuropathy, and vascular risk
      factors except for DM and hyperlipidemia were included in the study. DWMLs and
      carotid atherosclerosis were investigated in patients with and without
      polyneuropathy. Forty patients (60.6%) had diabetic sensorimotor polyneuropathy.
      DWMLs were more frequent in patients with polyneuropathy compared to patients
      without polyneuropathy (p = 0.003). Logistic regression analysis confirmed
      association between polyneuropathy and DWMLs after adjusted for age (p = 0.013),
      duration of DM (p = 0.007), and both age and duration of DM (p = 0.016). No
      statistically significant difference was found between patients with and without
      polyneuropathy for carotid atherosclerosis. Among patients with polyneuropathy,
      those having DWMLs had higher mean age (p = 0.003) and longer symptom duration (p
      = 0.020) compared to patients without DWMLs. No association was found between
      DWMLs and carotid atherosclerosis. Polyneuropathy and cerebral DWMLs in type 2 DM
      patients may share common pathogenesis; presence and duration of polyneuropathy
      symptoms may predict ischemic white matter damage independent of carotid
      atherosclerosis.

PMID- 29063452
TI  - The Italian version of cognitive function instrument (CFI): reliability and
      validity in a cohort of healthy elderly.
AB  - The Alzheimer's disease Cooperative Study (ADCS)-Cognitive Function Instrument
      (CFI) is a 14-item questionnaire administered to the subject and the referent,
      aimed at detecting early changes in cognitive and functional abilities in
      individuals without clinical impairment. It is used for monitoring annual
      variations in cognitive functioning in prevention trials. The aim of the present
      study was to validate the Italian version of the CFI. A consecutive series of 257
      functionally independent subjects was recruited among relatives of patients or as
      volunteers. They were administered CFI and global cognition measurements: Mini
      Mental Status Examination (MMSE) and Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS). The reliability and criterion validity were
      comparable to the original in both self- and partner-report. Similarly to what
      reported in the original version, we found a corrected item-total correlation
      ranging between 0.38 and 0.54 in self-report and between 0.33 and 0.64 in partner
      report. Cronbach's alpha was 0.77 (95% CI 0.72-0.83) in self-report and 0.78 (95%
      CI 0.73-0.84) in partner-report. Total partner- and self-report scores were
      significantly correlated (rS = 0.31, p < 0.001). CFI self-report and CFI total
      score (partner + self-report) were negatively correlated with MMSE (rS = - 0.15,
      p = 0.022; rS = - 0.17, p = 0.008) and RBANS (rS = - 0.22, p < 0.001; rS = -
      0.25, p < 0.001). Analogous trends were found in the partner score, with a
      correlation with RBANS (rS = - 0.17, p = 0.014) and MMSE (rS = - 0.11, p =
      0.071). Our results support the reliability and validity of the Italian version
      of CFI. In order to definitely propose the use of CFI for tracking longitudinal
      changes of cognitive and functional abilities in subjects without clinical
      impairment, data from the follow-up of this cohort are needed.

PMID- 29063453
TI  - Right-to-left shunt may be prone to affect the white matter integrity of
      posterior circulation in migraine without aura.
AB  - Numerous studies have indicated an association between migraine and right-to-left
      shunt. However, little is known about whether right-to-left shunt has an effect
      on the migraine brain. This observational study aims to explore the impact of
      right-to-left shunt on the brain of migraine without aura on microstructural
      level. Thirty-five patients with migraine without aura were enrolled in this
      study. Contrast-enhanced Transcranial Doppler was performed to evaluate the
      status of right-to-left shunt. Three-dimensional T1-weighted and diffusion tensor
      images were acquired for data analysis. We employed voxel-based morphometry and
      tract-based spatial statistical analyses to assess the differences of gray and
      white matter between migraineurs with and without right-to-left shunt,
      respectively. Among the 35 patients, 19 (54.3%) patients had right-to-left shunt.
      There were no significant differences in headache features between migraineurs
      with and without right-to-left shunt. There were significant increases of mean
      and radial diffusivity in migraineurs with right-to-left shunt compared with
      migraineurs without right-to-left shunt. The alterations were primarily located
      in the right posterior thalamic radiation, secondly in the body of corpus
      callosum and the right superior corona radiata. No significant differences were
      observed in values of fractional anisotropy and axial diffusivity. No significant
      between-group differences were found in gray matter volume. Right-to-left shunt
      may cause alterations of white matter integrity in migraine without aura, and the
      alterations are more likely to be located at the posterior circulation.

PMID- 29063455
TI  - "Double scleral tunnel in tandem" technique for glaucoma drainage tube implants.
AB  - PURPOSE: To describe a new technique of Ahmed glaucoma valve implantation in
      patients with refractory glaucoma and present the long-term results. METHODS:
      Twenty-eight eyes of 28 patients with refractory glaucoma participated in the
      study. "Double scleral tunnel in tandem" technique was used for glaucoma valve
      implantation in all patients. The technique consists of the formation of two
      scleral tunnels in tandem so as to completely cover the extraocular part of
      valve's tube and facilitate a parallel to the iris placement of the intraocular
      part of the tube. RESULTS: Postoperative hypotony developed in two (7.1%) cases
      which resolved within 3 days in all cases. One (3.6%) eye manifested
      postoperative hyphema that resolved without complications within a week, and two
      (7.1%) cases presented with exposure of the tube. The average highest
      postoperative intraocular pressure (IOP) during the follow-up period was 19 mmHg
      (range 8-38 mmHg) without medications, and the average IOP at the last follow-up
      visit was 14.5 mmHg (range 8-22 mmHg). Additional treatment for IOP control was
      necessary in 11 (39.3%) cases. The average follow-up period was 60 months.
      CONCLUSION: This novel technique was found to be easy to master, effective and
      with low cost and rate of complications.

PMID- 29063456
TI  - Prompt 27-gauge sutureless transconjunctival vitrectomy for bleb-associated
      endophthalmitis.
AB  - PURPOSE: To summarize the characters of 6 bleb-associated endophthalmitis (BAE)
      cases and to report the outcomes of prompt 27-gauge sutureless transconjunctival
      vitrectomy to treat these cases. METHODS: Retrospective, non-randomized,
      consecutive case series of patients diagnosed with bleb-associated
      endophthalmitis who underwent prompt 27-gauge vitrectomy. RESULTS: The interval
      to get bleb-associated endophthalmitis from previous surgery was variant from 2
      weeks to 36 months. Most of the patients experienced eye pain. The visual acuity
      was affected quickly. All the patients presented with hypopyon, fibrinous
      reaction, and vitreous wick. The size of the hypopyon was from 2 to 4 mm. Two
      patients came with intraocular lenses. Prompt 27-gauge sutureless
      transconjunctival vitrectomy was performed on all patients with bleb-associated
      endophthalmitis. None of the patients experienced complications of sutureless
      vitrectomy such as hypotony or wound leak. The improvement of best corrected
      visual acuity (BCVA) was significant in four of six patients. The improvement of
      BCVA was statistically calculated by using logMAR VA (p < 0.01). The intraocular
      pressure (IOP) in all six patients reduced after the surgery. At 6 months' follow
      up, four patients with diffuse blebs had normal IOPs while two patients with
      cystic or encapsulated blebs had uncontrolled IOPs (> 21 mmHg) and received
      pressure-lowering agents. CONCLUSIONS: BAE is associated with substantial visual
      morbidity. Prompt 27-gauge sutureless transconjunctival vitrectomy is an
      effective and safe way for treating bleb-associated endophthalmitis.

PMID- 29063457
TI  - Hydrogeochemical processes identification and groundwater pollution causes
      analysis in the northern Ordos Cretaceous Basin, China.
AB  - It is necessary to identify the hydrogeochemical processes and analyze the causes
      of groundwater pollution due to the lack of knowledge about the groundwater
      chemical characteristics and the endemic diseases caused by groundwater pollution
      in the northern Ordos Cretaceous Basin. In this paper, groundwater chemical
      facies were obtained using the piper trilinear diagram based on the analysis of
      190 samples. The hydrogeochemical processes were identified using ionic ratio
      coefficient, such as leaching, evaporation and condensation. The causes and
      sources of groundwater pollution were analyzed by correspondence analysis, and
      the spatial distribution and enrichment reasons of fluoride ion were analyzed
      considering the endemic fluorosis emphatically. The results show that leaching,
      evaporation and condensation, mixing, and anthropogenic activities all had
      significant impact on hydrogeochemical processes in the study area. However,
      cation exchange and adsorption effects were strong in the S2 and S3 groundwater
      flow systems, but weak in S1. Groundwater is mainly polluted by Mn and CODMn in
      the study area. The landfill leachate, domestic sewage, and other organic
      pollutants, excessive use of pesticides and fertilizers in agriculture, and
      pyrite oxidation from long-term and large-scale exploitation of coal are the
      sources of groundwater pollution. The S1 has the highest degree of groundwater
      pollution, followed by S2 and S3. High concentration of fluoride ion is mainly
      distributed in the north and west of study area. Evaporation and condensation and
      groundwater chemistry component are the most important causes of fluoride ion
      enrichment. The results obtained in this study will be useful for understanding
      the groundwater quality for effective management and utilization of groundwater
      resources and assurance of drinking water safety.

PMID- 29063458
TI  - Geochemical fractions and phytoavailability of Zinc in a contaminated calcareous
      soil affected by biotic and abiotic amendments.
AB  - Many studies have conducted to determine the best management practice to reduce
      the mobility and phytoavailability of the trace metals in contaminated soils. In
      this study, geochemical speciation and phytoavailability of Zn for sunflower were
      studied after application of nanoparticles (SiO2 and zeolite, with an application
      rate of 200 mg kg-1) and bacteria [Bacillus safensis FO-036b(T) and Pseudomonas
      fluorescens p.f.169] to a calcareous heavily contaminated soil. Results showed
      that the biotic and abiotic treatments significantly reduced the Zn concentration
      in the aboveground to non-toxicity levels compared to the control treatment, and
      the nanoparticle treatments were more effective than the bacteria and control
      treatments. The concentration of CaCl2-extractable Zn in the treated soils was
      significantly lower than those of the control treatment. The results of
      sequential extraction showed that the maximum portion of total Zn belonged to the
      fraction associated with iron and manganese oxides. On the contrary, the minimum
      percent belonged to the exchangeable and water-soluble Zn (F1). From the
      environmental point of view, the fraction associated with iron and manganese
      oxides is less bioavailable than the F1 and carbonated fractions. On the basis of
      plant growth promotion, simultaneous application of the biotic and abiotic
      treatments significantly increased the aboveground dry biomass yield and also
      significantly reduced the CaCl2-extractable form, uptake by aboveground and
      translocation factor of Zn compared to the control treatment. Therefore, it might
      be suggested as an efficient strategy to promote the plant growth and reduce the
      mobile and available forms of toxic metals in calcareous heavily contaminated
      soils.

PMID- 29063454
TI  - Acute Effects of Dynamic Stretching on Muscle Flexibility and Performance: An
      Analysis of the Current Literature.
AB  - Stretching has long been used in many physical activities to increase range of
      motion (ROM) around a joint. Stretching also has other acute effects on the
      neuromuscular system. For instance, significant reductions in maximal voluntary
      strength, muscle power or evoked contractile properties have been recorded
      immediately after a single bout of static stretching, raising interest in other
      stretching modalities. Thus, the effects of dynamic stretching on subsequent
      muscular performance have been questioned. This review aimed to investigate
      performance and physiological alterations following dynamic stretching. There is
      a substantial amount of evidence pointing out the positive effects on ROM and
      subsequent performance (force, power, sprint and jump). The larger ROM would be
      mainly attributable to reduced stiffness of the muscle-tendon unit, while the
      improved muscular performance to temperature and potentiation-related mechanisms
      caused by the voluntary contraction associated with dynamic stretching.
      Therefore, if the goal of a warm-up is to increase joint ROM and to enhance
      muscle force and/or power, dynamic stretching seems to be a suitable alternative
      to static stretching. Nevertheless, numerous studies reporting no alteration or
      even performance impairment have highlighted possible mitigating factors (such as
      stretch duration, amplitude or velocity). Accordingly, ballistic stretching, a
      form of dynamic stretching with greater velocities, would be less beneficial than
      controlled dynamic stretching. Notwithstanding, the literature shows that
      inconsistent description of stretch procedures has been an important deterrent to
      reaching a clear consensus. In this review, we highlight the need for future
      studies reporting homogeneous, clearly described stretching protocols, and
      propose a clarified stretching terminology and methodology.

PMID- 29063459
TI  - Tension pneumopericardium following suicidal stab wounds to the chest.
AB  - Pneumopericardium (PPC) and Tension Pneumopericardium (TPPC) refer to collections
      of gas in the pericardial cavity, the latter resulting in air tamponade and
      cardiac compromise. Following penetrating chest injuries, PPC and TPPC appear to
      be uncommon findings associated with a high mortality and correlated with other
      thoracic trauma. Diagnosis of PPC and TPPC is difficult relying on conventional
      autopsy alone, while postmortem computed tomography (PMCT) shows a high
      sensitivity for the detection of internal gas collections. Possibly due to
      difficulty in detection, PPC and TPPC have not been discussed from a forensic
      point of view and many lethal cases of PPC and TPPC might have been missed in
      medicolegal investigations. In this report, we present a case with suicidal,
      penetrating stab wounds to the chest resulting in a TPPC with lethal air
      tamponade documented by PMCT.

PMID- 29063460
TI  - Copper-beaten skull appearance in the setting of Marfan syndrome.

PMID- 29063461
TI  - A case of sudden death due to spontaneous right subclavian artery dissection.
AB  - Acute subclavian artery dissection (SAD) is a rare entity which is usually
      associated with several vascular abnormalities and traumatic events. Spontaneous
      SAD remains exceptional and often affects the left artery. We report the autopsy
      case of a 29-year-old female who died suddenly following a spontaneous dissection
      of the right subclavian artery.

PMID- 29063462
TI  - The role of microalbuminuria as a predictor of subclinical cardiovascular events
      in rheumatoid arthritis patients and its relation to disease activity.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that
      affects many body tissues and leads to major morbidity and mortality. Renal
      disease in RA is clinically important because it restricts the management of
      primary disease and increases mortality. The objectives of this study are to (1)
      investigate the difference between RA patients with and without microalbuminuria
      (MAU) and (2) find out the relation between MAU and disease activity as well as
      subclinical cardiovascular effects. Ninety RA patients were divided into two
      groups according to the presence of MAU, in addition to 30 healthy volunteers.
      ESR, hs-CRP, RF, lipid profile, urinary microalbumin, GFR, renal function tests,
      carotid intima media thickness (cIMT), flow-mediated dilatation of the brachial
      artery (FMD), ECG, and echocardiographic examination were performed for patients
      and controls. MAU positive RA patients revealed significantly higher lipid
      profile, ESR, hs-CRP, DAS 28, cIMT, and lower FMD as well as ECG and
      echocardiographic abnormalities compared to MAU negative RA patients. Moreover,
      there was significant positive correlation between MAU and DAS28, hs-CRP, LDL,
      cIMT as well as negative correlation with FMD%. In our study, all RA patients
      with MAU had a normal serum creatinine concentration and gave a negative result
      with Albustix. MAU is significantly correlated with ESR, hs-CRP, lipid profile,
      cIMT, and FMD% in RA patients; therefore, it can be used as an index to measure
      disease activity as well as subclinical cardiovascular affection in RA patients.

PMID- 29063463
TI  - Prevalence of depression and anxiety in rheumatoid arthritis patients and their
      associations with serum vitamin D level.
AB  - Vitamin D deficiency may be associated with depression in the general population.
      This study aimed to describe the prevalence of depression and anxiety in
      rheumatoid arthritis (RA) patients from Northwestern China and identify
      associations of Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale
      (HAMA) scores with serum vitamin D level in these patients. We recruited 161 RA
      patients inform the First Affiliated Hospital of Xi'an Jiaotong University during
      Nov. 2016 to Feb. 2017. All patients completed a survey including HAMD and HAMA
      scales. RA activity (DAS28) was scored by a rheumatologist, and serum 25-OH-D3
      levels were measured by electrochemiluminescence immunoassay. The data were
      analyzed using the SPSS16.0 based on "possible and probable" cut points for HAMD
      and HAMA. About 62 and 60% of patients had some degrees of depression and
      anxiety, respectively. The mean of serum 25-OH-D3 levels in RA patients with
      depression was 15.24 +/- 8.78 ng/mL, which was significantly lower than those
      without depression (24.68 +/- 10.98 ng/mL, p = 0.009). Despite negative
      correlations between serum 25-OH-D3 level and the score of HAMD (r = - 0.520, p <
      0.001) or HAMA (r = - 0.469, p < 0.001), there was a positive correlations
      between DAS28and the score of HAMD (r = 0.459, p = 0.001) or HAMA (r = 0.486, p <
      0.001). The multivariate logistic regression showed that disease duration, serum
      25-OH-D3 level, and treatment of tumor necrosis factor inhibitor were associated
      with depression/anxiety in RA patients. Our study shows a high prevalence of
      depression and anxiety in RA patients from Northwestern China. Both disease
      activity of RA and low serum 25-OH-D3 level are associated with the severity of
      depression and anxiety. It is imperative for clinicians to screen hypovitaminosis
      of vitamin D and depression/anxiety in RA patients.

PMID- 29063465
TI  - Are cost differences between specialist and general hospitals compensated by the
      prospective payment system?
AB  - Prospective payment systems fund hospitals based on a fixed-price regime that
      does not directly distinguish between specialist and general hospitals. We
      investigate whether current prospective payments in England compensate for
      differences in costs between specialist orthopaedic hospitals and trauma and
      orthopaedics departments in general hospitals. We employ reference cost data for
      a sample of hospitals providing services in the trauma and orthopaedics
      specialty. Our regression results suggest that specialist orthopaedic hospitals
      have on average 13% lower profit margins. Under the assumption of break-even for
      the average trauma and orthopaedics department, two of the three specialist
      orthopaedic hospitals appear to make a loss on their activity. The same holds
      true for 33% of departments in our sample. Patient age and severity are the main
      drivers of such differences.

PMID- 29063464
TI  - Diverse patterns of anti-TNF-alpha-induced lupus: case series and review of the
      literature.
AB  - The induction of autoantibodies is common following therapy with anti-TNF-alpha
      agents. However, anti-TNF-alpha-induced lupus (ATIL) is rare. We assessed the
      clinical characteristics of three patients with inflammatory bowel disease (IBD)
      who were treated with infliximab and developed distinct subsets of ATIL. Also, we
      searched for similar cases in the published literature. We describe three
      patients with ATIL. The first patient had a classical drug-induced lupus (DIL)
      presented by thrombocytopenia that resolved after infliximab discontinuation. The
      second case experienced symmetric polyarthritis of 14 joints in rheumatoid
      arthritis (RA)-like distribution accompanied by lymphopenia. The third one had a
      severe serositis including ascites and pleural and pericardial effusions along
      with pancytopenia. In this patient, ATIL coexisted with anti-TNF-alpha-induced
      hepatitis. The second and third patients met the American College of Rheumatology
      classification criteria for SLE. Nevertheless, all three cases exhibited ANA and
      anti-dsDNA positivity, and only the second patient had anticardiolipin (aCL IgG)
      and anti-histone antibodies. The coexistence of both lupus-like syndrome and
      hepatitis following anti-TNF-alpha therapy in the same patient is very rare, and
      to the best of our knowledge, only four such case reports are mentioned in
      literature. Patients with mild ATIL may tolerate another anti-TNF-alpha agent
      without recurrence of the disease. Rheumatologists should be aware of the
      distinct clinical presentations of ATIL and its coexistence with other rare anti
      TNF-alpha complications such as hepatitis.

PMID- 29063466
TI  - Understanding and improving decisions in clinical medicine (III): towards
      cognitively informed clinical thinking.

PMID- 29063468
TI  - Different Survival Benefits of Chinese Medicine for Pancreatic Cancer: How to
      Choose?
AB  - OBJECTIVE: To assess the efficacy of Chinese medicine (CM) on patients with
      pancreatic cancer (PC) in a retrospective population-based study. METHODS:
      Between January 1, 2013, and August 30, 2016, according to whether received
      Western medicine treatment, the patients were included into either integrative
      medicine (IM) group or CM group. All enrolled patients were orally administrated
      with Gexia Zhuyu Decoction () or Liujun Ermu Decoction () by syndrome
      differentiation, twice a day, last for at least 2 months. The primary end point
      was overall survival (OS). RESULTS: A total of 174 patients with PC were enrolled
      in this study. In stage I/II, the median OS was 20.5 months in the IM group [95%
      confidence interval (CI), 12.499 to 28.501] and 11.17 months in the CM group (95%
      CI, 5.160 to 17.180, P=0.015). The 1- and 2-year survival rates for the two
      groups were 47.0%, 40.0% and 21.0%, 21.0%, respectively. In stage III/IV, median
      OS was 13.53 months (95% CI, 8.665 to 18.395) in the IM group versus 6.4 months
      (95% CI, 0.00 to 15.682) in the CM group, respectively (P=0.32). The 1- and 2
      year survival rate for the IM and CM groups were 27.0%, 7.0% and 20.0%, 2.0%,
      respectively. CONCLUSIONS: Intervention of CM contributes to the different
      survival benefits for PC in different stages. Multimodality treatment might be a
      promising strategy for PC patients in early stage. While, in advanced stage, CM
      might be an alternative candidate for PC patients.

PMID- 29063467
TI  - Correlations between dopamine transporter density measured by 123I-FP-CIT SPECT
      and regional gray matter volume in Parkinson's disease.
AB  - PURPOSE: Parkinson's disease (PD) is caused by a selective degeneration of
      dopamine neurons. The relationship between dopamine transporter (DAT) density and
      gray matter volume has been unclear. Here we investigated the voxelwise
      correlation between gray matter volume and DAT binding measured by 123I-N-omega
      fluoropropyl-2beta-carboxymethoxy-3beta-(4-iodophenyl)nortropane (123I-FP-CIT)
      single-photon emission computed tomography (SPECT; DaTscanTM imaging) in PD.
      MATERIALS AND METHODS: Thirty-one male patients with PD were examined with MRI
      and DaTscan. To measure nigrostriatal dopaminergic degeneration in PD, the
      specific binding ratio (SBR) of the striatum was obtained by DaTscan. Voxel-based
      morphometry (VBM) of 3D T1-weighted images was used to evaluate the relationships
      between the regional gray matter volume and the SBR in the striatum. RESULTS:
      There were significant positive correlations between the SBR and the gray matter
      volume in the right pulvinar and posterior middle temporal gyrus and a trend
      level in the left pulvinar, all of which are associated with the second visual
      pathway. CONCLUSION: The nigrostriatal dopaminergic degeneration might affect the
      secondary visual pathway, leading to visual dysfunctions in PD.

PMID- 29063469
TI  - Effect of modified Wuzi Yanzong Pill () on Tip60-mediated apoptosis in testis of
      male rats after microwave radiation.
AB  - OBJECTIVE: To investigate the effect of a modified Wuzi Yanzong Pill (, WZYZP) on
      the male rats' testis after microwave radiation, as well as its potential
      mechanism. METHODS: Forty-five male rats were randomly assigned to three groups:
      the control group, the radiation group, and the WZYZP group. The rats in the
      radiation group and WZYZP group were exposed to microwave radiation for 15 min
      once, while the rats in the control group were not exposed to any radiation. The
      rats in the WZYZP group were given a modified of WZYZP by gavage daily for 7
      days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl
      transferase mediated nick end labeling (TUNEL) assay. Histopathological
      alterations of the testis were observed by haematoxylin-eosin (HE) staining. Tat
      interactive protein, 60kD (Tip60) and p53 expressions were determined by Western
      blotting. RESULTS: The apoptosis index (AI) in the radiation group was higher
      than that of the WZYZP group and control group on day 1 (D1), day 7 (D7) day 14
      (D14) after radiation (P<0.05). The seminiferous tubules were of normal
      morphology in the control group. In the radiation group, the partial seminiferous
      tubules were collapsed, basement membranes of the seminiferous epithelia became
      detached. WZYZP could restore the morphological changes. There was no expression
      of Tip60 among the three groups on D7 and D14. The expression of p53 was higher
      in the radiation group than in the control group (P<0.05). WZYZP could down
      regulate the rising p53 induced by radiation on D7 and D14 (P<0.05). CONCLUSION:
      A modified WZYZP may affect germ cells, and its protective effects may partly
      result from its ability to intervene in Tip60 mediated apoptosis.

PMID- 29063470
TI  - Characteristics of American scholars' research on Chinese medical classics and
      their contributions.
AB  - Chinese medical classics are important carriers for the inheritance, innovation
      and development of academic thoughts of Chinese medicine (CM), containing rich
      thoughts on diagnosis and treatment as well as therapeutic principles of CM. The
      international exchange of CM has a very long history. With the development of
      society, Western scholars in modern times are deepening their researches on
      Chinese medical classics. This would provide a new way for promoting CM in
      Western countries to investigate researches made by famed American scholars and
      their academic viewpoints.

PMID- 29063472
TI  - Effects of photobiomodulation on experimental models of peripheral nerve injury.
AB  - Phototherapy has demonstrated positive effects in the treatment of peripheral
      nerve injury, but there is a need to investigate the dosimetric parameters. Thus,
      the aim of the present study was to conduct a literature review on the effects of
      photobiomodulation with the use of low-level laser therapy (LLLT) on the
      treatment of peripheral nerve injury in experimental models. The databases of
      PubMed/MEDLINE, SCOPUS, and SPIE Digital Library were searched for articles on
      the use of LLLT in experimental models of peripheral nerve injury published in
      English between January 2007 and March 2016. The laser parameter variability was
      wavelength (632.8 to 980 nm), power (10 to 190 mW), and total energy (0.15 to 90
      J) in pulsed or continuous wave and single or multiple points. Eighteen original
      articles demonstrating the effects of LLLT on the acceleration of functional
      recovery, morphological aspects as well as the modulation of the expression
      inflammatory cytokines, and growth factors were selected. LLLT is a viable
      phototherapeutic modality for the treatment of peripheral nerve injury,
      demonstrating positive effects on the neuromuscular repair process using either
      red or infrared light. The majority of studies used a power of up to 50 mW and
      total energy of up to 15 J administered to multiple points. The determination of
      these parameters is important to the standardization of a LLLT protocol to
      enhance the regeneration process following a peripheral nerve injury.

PMID- 29063473
TI  - Comparing aspheric ablation profile with standard corneal ablation for correction
      of myopia and myopic astigmatism, a contralateral eye study.
AB  - The purpose of this study is to compare visual outcomes of myopic refractive
      surgery, using tissue saving (TS), a standard ablation profile by a Technolas
      217z100, and aberration smart ablation (ASA), an aspheric algorithm by a MEL 80
      excimer laser in two eyes of one patient. In this prospective interventional
      paired-eye controlled study, a total of 100 eyes of 50 participants with myopia
      with or without astigmatism underwent thin-flap Femto-LASIK, using a Femto LDV
      femtosecond laser (Ziemer Ophthalmic Systems AG, Port, Switzerland). For each
      patient, one eye was randomly treated with tissue-saving algorithm (TS group) by
      the Technolas 217z100 excimer laser and the other eye was treated with optimized
      smart ablation profile (ASA group) by the MEL 80 excimer laser. Outcome measures
      were uncorrected distance visual acuities (UDVAs), corrected distance visual
      acuities (CDVAs), manifest refraction, higher-order aberrations (HOAs), contrast
      sensitivity, and patient satisfaction 12 months after surgery. At 12 months
      postoperative, "45 subjects returned with mean" UDVA was - 0.02 +/- 0.08
      Logarithm of mean angle of resolution (LogMAR) for TS group and - 0.02 +/- 0.09
      LogMAR for ASA group (P = 0.91). Of the TS eyes, 42/45 (93.3%) and 32/45 (71.1%)
      were within +/- 0.5 D and +/- 0.25 D of target refraction, respectively, and of
      the ASA eyes, 41/45 (91.1%) and 30/45 (66.6%) were within +/- 0.5 D and +/- 0.25
      D of target refraction, respectively. No statistically significant differences
      were observed between groups in HOAs changes and contrast sensitivity function.
      Aspheric and non-aspheric LASIKs using the two different excimer lasers provide
      similar results in myopic and myopic astigmatism patients.

PMID- 29063471
TI  - Granulocyte Colony-Stimulating Factor (G-CSF) for the Treatment of Spinal Cord
      Injury.
AB  - Spinal cord injury (SCI) is a common medical condition with a poor prognosis for
      recovery and catastrophic effects on a patient's quality of life. Available
      treatments for SCI are limited, and the evidence suggesting their harmful side
      effects is more consistent than any suggestion of clinical benefit. Developing
      novel safe and effective therapeutic options for SCI is crucial. Granulocyte
      colony-stimulating factor (G-CSF) is a hematopoietic cytokine with known
      multifaceted effects on the central nervous system. Herein, we review the
      accumulating preclinical evidence for the beneficial effects of G-CSF on
      functional and structural outcomes after SCI. Meanwhile we present and discuss
      multiple mechanisms for G-CSF's neuroprotective and neuroregenerative actions
      through the results of these studies. In addition, we present the available
      clinical evidence indicating the efficacy and safety of G-CSF administration for
      the treatment of acute and chronic traumatic SCI, compression myelopathy, and SCI
      associated neuropathic pain. Our review indicates that although the quality of
      clinical evidence regarding the use of G-CSF in SCI is inadequate, the
      encouraging available preclinical and clinical data warrant its further clinical
      development, and bring new hope to the longstanding challenge that is treatment
      of SCI.

PMID- 29063474
TI  - Dispersion of near-infrared laser energy through radicular dentine when using
      plain or conical tips.
AB  - The aim of this study was to investigate the influence of tip design on patterns
      of laser energy dispersion through the dentine of tooth roots when using near
      infrared diode lasers. Diode laser emissions of 810 or 940 nm were used in
      combination with optical fiber tips with either conventional plain ends or
      conical ends, to irradiate tooth roots of oval or round cross-sectional shapes.
      The lasers were operated in continuous wave mode at 0.5 W for 5 s with the distal
      end of the fiber tip placed in the apical or coronal third of the root canal at
      preset positions. Laser light exiting through the roots and apical foramen was
      imaged, and the extent of lateral spread calculated. There was a significant
      difference in infrared light exiting the root canal apex between plain and
      conical fiber tips for both laser wavelengths, with more forward transmission of
      laser energy through the apex for plain tips. For both laser wavelengths, there
      were no significant differences in emission patterns when the variable of canal
      shape was used and all other variables were kept the same (plain vs conical tip,
      tip position). To ensure optimal treatment effect and to prevent the risks of
      inadvertent laser effects on the adjacent periapical tissues, it is important to
      have a good understanding of laser transmission characteristics of the root canal
      and root dentine. Importantly, it is also essential to understand transmission
      characteristics of plain and conical fibers tips.

PMID- 29063475
TI  - Structural Transformation Detection Contributes to Screening of Behaviorally
      Active Compounds: Dynamic Binding Process Analysis of DhelOBP21 from Dastarcus
      helophoroides.
AB  - In light of reverse chemical ecology, the fluorescence competitive binding assays
      of functional odorant binding proteins (OBPs) is a recent advanced approach for
      screening behaviorally active compounds of insects. Previous research on
      Dastareus helophoroides identified a minus-C OBP, DhelOBP21, which preferably
      binds to several ligands. In this study, only (+)-beta-pinene proved attractive
      to unmated adult beetles. To obtain a more in-depth explanation of the lack of
      behavioral activity of other ligands we selected compounds with high (camphor)
      and low (beta-caryophyllene) binding affinities. The structural transformation of
      OBPs was investigated using well-established approaches for studying binding
      processes, such as fluorescent quenching assays, circular dichroism, and
      molecular dynamics. The dynamic binding process revealed that the flexibility of
      DhelOBP21 seems conducive to binding specific ligands, as opposed to broad
      substrate binding. The compound (+)-beta-pinene and DhelOBP21 formed a stable
      complex through a secondary structural transformation of DhelOBP21, in which its
      amino-terminus transformed from random coil to an alpha-helix to cover the
      binding pocket. On the other hand, camphor could not efficiently induce a stable
      structural transformation, and its high binding affinities were due to strong
      hydrogen-bonding, compromising the structure of the protein. The other compound,
      beta-caryophyllene, only collided with DhelOBP21 and could not be positioned in
      the binding pocket. Studying structural transformation of these proteins through
      examining the dynamic binding process rather than using approaches that just
      measure binding affinities such as fluorescence competitive binding assays can
      provide a more efficient and reliable approach for screening behaviorally active
      compounds.

PMID- 29063477
TI  - Easy, Fast, and Reproducible Quantification of Cholesterol and Other Lipids in
      Human Plasma by Combined High Resolution MSX and FTMS Analysis.
AB  - Reliable, cost-effective, and gold-standard absolute quantification of non
      esterified cholesterol in human plasma is of paramount importance in clinical
      lipidomics and for the monitoring of metabolic health. Here, we compared the
      performance of three mass spectrometric approaches available for direct detection
      and quantification of cholesterol in extracts of human plasma. These approaches
      are high resolution full scan Fourier transform mass spectrometry (FTMS)
      analysis, parallel reaction monitoring (PRM), and novel multiplexed MS/MS (MSX)
      technology, where fragments from selected precursor ions are detected
      simultaneously. Evaluating the performance of these approaches in terms of
      dynamic quantification range, linearity, and analytical precision showed that the
      MSX-based approach is superior to that of the FTMS and PRM-based approaches. To
      further show the efficacy of this approach, we devised a simple routine for
      extensive plasma lipidome characterization using only 8 MUL of plasma, using a
      new commercially available ready-to-spike-in mixture with 14 synthetic lipid
      standards, and executing a single 6 min sample injection with combined MSX
      analysis for cholesterol quantification and FTMS analysis for quantification of
      sterol esters, glycerolipids, glycerophospholipids, and sphingolipids. Using this
      simple routine afforded reproducible and absolute quantification of 200 lipid
      species encompassing 13 lipid classes in human plasma samples. Notably, the
      analysis time of this procedure can be shortened for high throughput-oriented
      clinical lipidomics studies or extended with more advanced MSALL technology
      (Almeida R. et al., J. Am. Soc. Mass Spectrom. 26, 133-148 [1]) to support in
      depth structural elucidation of lipid molecules. Graphical Abstract ?.

PMID- 29063476
TI  - Fungal beta-Glucan Activates the NLRP3 Inflammasome in Human Bronchial Epithelial
      Cells Through ROS Production.
AB  - The nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3)
      inflammasome has developed as an important bridge between innate immune and
      infection recently, and has the ability to drive proteolytic procaspase-1 into
      bioactive caspase-1, then responsible for proteolytic processing of inflammatory
      cytokines IL-1beta and IL-18. Fungal beta-glucan, a major component of fungal
      cell wall, triggers inflammatory response in multiple immune cells, but rarely
      described in epithelial cells. Also, the relationship between fungal beta-glucan
      and NLRP3 inflammasome is not clear yet. In this study, we first identified that
      curdlan, a large particulate beta-glucan, could activate the NLRP3 inflammasome
      in LPS-primed human bronchial epithelial cells (HBECs). RT-PCR and Western Blot
      showed that curdlan upregulate the mRNA as well as intracellular protein
      expression of NLRP3 and IL-1beta in HBECs, along with the activity of caspase-1,
      and the level of mature IL-1beta in cell supernatants was higher by ELISA
      detection. Further studies demonstrated that the activation of NLRP3 inflammasome
      could be attenuated by NAC, an inhibitor of ROS. Thus, it indicated curdlan
      activate NLRP3 inflammasome through a pathway requiring ROS production in HBECs.
      These findings may provide a new therapeutic target, NLRP3 inflammasome, in
      invasive pulmonary fungal infections.

PMID- 29063478
TI  - Effects of Magnetic and Electric Field Uniformity on Coded Aperture Imaging
      Quality in a Cycloidal Mass Analyzer.
AB  - Cycloidal mass analyzers are unique sector mass analyzers as they exhibit perfect
      double focusing, making them ideal for incorporating spatial aperture coding,
      which can increase the throughput of a mass analyzer without affecting the
      resolving power. However, the focusing properties of the cycloidal mass analyzer
      depend on the uniformity of the electric and magnetic fields. In this paper,
      finite element simulation and charged particle tracing were used to investigate
      the effect of field uniformity on imaging performance of a cycloidal mass
      analyzer. For the magnetic field, we evaluate a new permanent magnet geometry by
      comparing it to a traditional geometry. Results indicate that creating an
      aperture image in a cycloidal mass spectrometer with the same FWHM as the slit
      requires less than 1% variation in magnetic field strength along the ion
      trajectories. The new magnet design, called the opposed dipole magnet, has less
      than 1% field variation over an area approximately 62 * 65 mm; nearly twice the
      area available in a traditional design of similar size and weight. This allows
      ion imaging across larger detector arrays without loss of resolving power. In
      addition, we compare the aperture imaging quality of a traditionally used
      cycloidal mass spectrometer electric design with a new optimized design with
      improved field uniformity. Graphical abstract ?.

PMID- 29063479
TI  - Dyssynergic defecation: Demographics, symptoms, colonoscopic findings in north
      Indian patients.

PMID- 29063480
TI  - An update of pitfalls in prostate mpMRI: a practical approach through the lens of
      PI-RADS v. 2 guidelines.
AB  - OBJECTIVES: The aim of the current report is to provide an update in the imaging
      interpretation of prostate cancer on multiparametric magnetic resonance imaging
      (mpMRI), with a special focus on how to discriminate pathological tissue from the
      most common pitfalls that may be encountered during daily clinical practice using
      the Prostate Imaging Reporting and Data System (PI-RADS) version 2 guidelines.
      METHODS: All the cases that are shown in this pictorial review comply with the
      European Society of Urogenital Radiology (ESUR) guidelines for technical mpMRI
      requirements. RESULTS: Despite the standardised manner to report mpMRI (PI-RADS
      v. 2), some para-physiologic appearances of the prostate can mimic cancer. As
      such, it is crucial to be aware of these pitfalls, in order to avoid the
      under/overestimation of prostate cancer. CONCLUSIONS: A detailed knowledge of
      normal and abnormal findings in mpMRI of the prostate is pivotal for an accurate
      management of the wide spectrum of clinical scenarios that radiologists may
      encounter during their daily practice. TEACHING POINTS: * Some para-physiologic
      appearances of the prostate may mimic cancer. * Knowledge of normal and abnormal
      findings in prostate mpMRI is pivotal. * Any radiologist involved in prostate
      mpMRI reporting should be aware of pitfalls.

PMID- 29063481
TI  - Body composition determinants of radiation dose during abdominopelvic CT.
AB  - OBJECTIVES: We designed a prospective study to investigate the in-vivo
      relationship between abdominal body composition and radiation exposure to
      determine the strongest body composition predictor of dose length product (DLP)
      at CT. METHODS: Following institutional review board approval, quantitative
      analysis was performed prospectively on 239 consecutive patients who underwent
      abdominopelvic CT. DLP, BMI, volumes of abdominal adipose tissue, muscle, bone
      and solid organs were recorded. RESULTS: All measured body composition parameters
      correlated positively with DLP. Linear regression (R2 = 0.77) revealed that total
      adipose volume was the strongest predictor of radiation exposure [B (95% CI) =
      0.027(0.024-0.030), t=23.068, p < 0.001]. Stepwise linear regression using DLP as
      the dependent and BMI and total adipose tissue as independent variables
      demonstrated that total adipose tissue is more predictive of DLP than BMI [B (95%
      CI) = 16.045 (11.337-20.752), t=6.681, p < 0.001]. CONCLUSIONS: The volume of
      adipose tissue was the strongest predictor of radiation exposure in our cohort.
      MAIN MESSAGE: * Individual body composition variables correlate with DLP at
      abdominopelvic CT. * Total abdominal adipose tissue is the strongest predictor of
      radiation exposure. * Muscle volume is also a significant but weaker predictor of
      DLP.

PMID- 29063482
TI  - Information, Advocacy and Signposting as a Low-Level Support for Adults with High
      Functioning Autism Spectrum Disorder: An Example from the UK.
AB  - 'Low-level' support is championed to support adults with high functioning autism
      spectrum disorder (HFASD) to achieve good quality health and social care, yet
      research in the area is sparse. Drawing on semi-structured interview data, this
      paper considers the efficacy of an intervention to provide low-level support to
      adults with HFASD with little or no funded support. The intervention led to a
      number of perceived positive outcomes for adults with HFASD, their families, and
      service providers in the city, including increased access to education,
      volunteering, support and information, socialising, improved health and
      wellbeing, and managing day-to-day. Although many of life's difficulties still
      persisted, the intervention helped service users overcome barriers to availing
      further support, possibly leading to beneficial outcomes down the line.

PMID- 29063483
TI  - The Future of Contextual Fear Learning for PTSD Research: A Methodological Review
      of Neuroimaging Studies.
AB  - There has been a great deal of recent interest in human models of contextual fear
      learning, particularly due to the use of such paradigms for investigating neural
      mechanisms related to the etiology of posttraumatic stress disorder. However, the
      construct of "context" in fear conditioning research is broad, and the
      operational definitions and methods used to investigate contextual fear learning
      in humans are wide ranging and lack specificity, making it difficult to interpret
      findings about neural activity. Here we will review neuroimaging studies of
      contextual fear acquisition in humans. We will discuss the methodology associated
      with four broad categories of how contextual fear learning is manipulated in
      imaging studies (colored backgrounds, static picture backgrounds, virtual
      reality, and configural stimuli) and highlight findings for the primary neural
      circuitry involved in each paradigm. Additionally, we will offer methodological
      recommendations for human studies of contextual fear acquisition, including using
      stimuli that distinguish configural learning from discrete cue associations and
      clarifying how context is experimentally operationalized.

PMID- 29063484
TI  - MicroRNAs in Post-traumatic Stress Disorder.
AB  - Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop
      following exposure to or witnessing of a (potentially) threatening event. A
      critical issue is to pinpoint the (neuro)biological mechanisms underlying the
      susceptibility to stress-related disorder such as PTSD, which develops in the
      minority of ~15% of individuals exposed to trauma. Over the last few years, a
      first wave of epigenetic studies has been performed in an attempt to identify the
      molecular underpinnings of the long-lasting behavioral and mental effects of
      trauma exposure. The potential roles of non-coding RNAs (ncRNAs) such as
      microRNAs (miRNAs) in moderating or mediating the impact of severe stress and
      trauma are increasingly gaining attention. To date, most studies focusing on the
      roles of miRNAs in PTSD have, however, been completed in animals, using cross
      sectional study designs and focusing almost exclusively on subjects with
      susceptible phenotypes. Therefore, there is a strong need for new research
      comprising translational and cross-species approaches that use longitudinal
      designs for studying trajectories of change contrasting susceptible and resilient
      subjects. The present review offers a comprehensive overview of available studies
      of miRNAs in PTSD and discusses the current challenges, pitfalls, and future
      perspectives of this field.

PMID- 29063485
TI  - The Dissociative Subtype of Post-traumatic Stress Disorder: Research Update on
      Clinical and Neurobiological Features.
AB  - Recently, a dissociative subtype of post-traumatic stress disorder (PTSD) has
      been included in the DSM-5. This review focuses on the clinical and
      neurobiological features that distinguish the dissociative subtype of PTSD from
      non-dissociative PTSD. Clinically, the dissociative subtype of PTSD is associated
      with high PTSD severity, predominance of derealization and depersonalization
      symptoms, a more significant history of early life trauma, and higher levels of
      comorbid psychiatric disorders. Furthermore, PTSD patients with dissociative
      symptoms exhibit different psychophysiological and neural responses to the recall
      of traumatic memories. While individuals with non-dissociative PTSD exhibit an
      increased heart rate, decreased activation of prefrontal regions, and increased
      activation of the amygdala in response to traumatic reminders, individuals with
      the dissociative subtype of PTSD show an opposite pattern. It has been proposed
      that dissociation is a regulatory strategy to restrain extreme arousal in PTSD
      through hyperinhibition of limbic regions. In this research update, promises and
      pitfalls in current research studies on the dissociative subtype of PTSD are
      listed. Inclusion of the dissociative subtype of PTSD in the DSM-5 stimulates
      research on the prevalence, symptomatology, and neurobiology of the dissociative
      subtype of PTSD and poses a challenge to improve treatment outcome in PTSD
      patients with dissociative symptoms.

PMID- 29063486
TI  - Diagnosis and Management of Pancreatic Cystic Neoplasms.
AB  - OPINION STATEMENT: Pancreatic cystic neoplasms (PCNs) are being diagnosed with
      increasing frequency. PCNs have diverse presentations, natural history, and
      biological behavior. Obtaining an accurate diagnosis of the type of cyst and
      assessing the potential for malignancy are crucial in determining the appropriate
      management strategy. Cross-sectional imaging with computed tomography (CT) or
      magnetic resonance imaging (MRI), at experienced centers, is effective in
      defining the type of cyst as well as identifying high-risk features. Endoscopic
      ultrasound with fine-needle aspiration (EUS-FNA) and cyst fluid analysis can
      categorize and risk-stratify cysts and is the test of choice in selected
      patients. However, there is currently no "perfect" test and studies have
      demonstrated substantial misdiagnosis and over-treatment of benign cysts using
      standard clinical, imaging, and cyst fluid analyses. Patients with symptomatic
      cysts or cysts with high-risk features suggestive of malignancy should be
      considered for surgical resection. Patients with low-risk PCNs can be placed in
      surveillance protocols with interval imaging. Various gastrointestinal societies
      have put forth evidence- or consensus-based guidelines that provide a framework
      for management of PCNs. However, the management can be complex and should ideally
      be planned in a multidisciplinary fashion by experienced specialists. Recent
      investigations using molecular markers to risk-stratify cysts offer promise in
      the future for an effective and accurate management strategy.

PMID- 29063487
TI  - Targeting of circulating Th17 cells by beta-D-mannuronic acid (M2000) as a novel
      medication in patients with rheumatoid arthritis.
AB  - OBJECTIVE: This study aimed at investigating the inhibitory effect of beta-D
      mannuronic acid (M2000) on the Th17 circulating levels and IL-17 a related
      cytokine in rheumatoid arthritis (RA) patients. METHODS: The study included 27
      patients with RA who had failed response to treatment. All patients were treated
      orally by M2000 at a dose of 500 mg twice daily for 12 weeks (Clinical trial
      identifier: IRCT2014011213739N2). The patients based on anti-tumor necrosis
      factor alpha (TNFalpha) blocker treatment were classified into two groups
      (conventional group and etanercept group). They were then allowed to continue
      their treatment excluding non-steroidal anti-inflammatory drugs (NSAIDs). The
      frequency of circulating Th17 cells and IL-17 serum level were determined before
      and 12 weeks after M2000 therapy and were compared to the healthy controls by
      using flow cytometry analysis and ELISA method, respectively. RESULTS: At
      baseline, higher circulating Th17 and IL-17 serum levels were significantly
      observed in both groups of RA patients than in the healthy controls (all P <
      0.001). The frequency of Th17 cells significantly decreased in the conventional
      group as well as in the etanercept group after M2000 therapy but the level of
      reduction was higher in the conventional group compared to the etanercept group
      (P < 0.03 and P < 0.04, respectively). The IL-17 serum level significantly
      decreased in both groups after M2000 therapy (P < 0.01 and P < 0.02,
      respectively). Furthermore, the frequency of Th17 cells was positively correlated
      with Disease Activity Score (DAS28) (r = 0.34, P = 0.02). CONCLUSION: M2000 shows
      the inhibitory effect on the frequency of circulating Th17 cells as well as in
      the production of IL-17 in RA patients.

PMID- 29063488
TI  - Attenuation of nociceptive pain and inflammatory disorders by total steroid and
      terpenoid fraction of Euphorbia tirucalli Linn root in experimental in vitro and
      in vivo model.
AB  - The plant Euphorbia tirucalli Linn has been successfully used as a tribal folk
      medicine in India and Africa for the management of acute inflammatory, arthritic,
      nociceptive pain and asthmatic symptoms. The present study was conducted to
      assess the anti-inflammatory, analgesic, anti-asthmatic and anti-arthritic role
      of the total steroid and terpenoid rich fractions of the hydro-alcoholic extract
      of E. tirucalli root (STF-HAETR). STF-HAETR fraction demonstrated 71.25 +/- 2.5
      and 74.25 +/- 5.1% protection against acetic acid-induced pain and central
      neuropathic pain at 75 and 100 mg/kg doses, respectively. It showed 96.97%
      protection against acute inflammation at 100 mg/kg with 1.6-fold better activity
      than the standard drug. The fraction exhibited such efficacy via inhibition of
      proinflammatory cytokines TNF-alpha, IFN-gamma, by 61.12 and 65.18%,
      respectively, at 100 MUg/mL. Inhibition of cyclooxygenase and Nitric oxide
      synthase in a dose-dependent manner affirms its analgesic and anti-inflammatory
      activity. The spectrophotometric analysis reveals that STF-HAETR induces
      ameliorative effect against heat-induced denaturation of Bovine serum albumin
      (BSA) and exhibits significant anti-proteinase activity. The plant fraction also
      demonstrated anti-asthmatic activity by displaying 62.45% protection against
      histamine induced bronchoconstriction or dyspnoea. Our findings suggest that STF
      HAETR could be an effective safe therapeutic agent to treat nociceptive pain,
      acute inflammation, asthma, and arthritis which may authenticate its traditional
      use.

PMID- 29063489
TI  - Mesenchymal stromal cells modulate gut inflammation in experimental colitis.
AB  - Inflammatory bowel diseases (IBDs) affect millions of people worldwide and their
      frequencies in developed countries have increased since the twentieth century. In
      this context, there is an intensive search for therapies that modulate
      inflammation and provide tissue regeneration in IBDs. Recently, the
      immunomodulatory activity of adipose tissue-derived mesenchymal stromal cells
      (ADMSCs) has been demonstrated to play an important role on several immune cells
      in different conditions of inflammatory and autoimmune diseases. In this study,
      we explored the immunomodulatory potential of ADMSC in a classical model of DSS
      induced colitis. First, we found that treatment of mice with ADMSC ameliorated
      the severity of DSS-induced colitis, reducing colitis pathological score and
      preventing colon shortening. Moreover, a prominent reduction of pro-inflammatory
      cytokines levels (i.e., IFN-gamma, TNF-alpha, IL-6 and MCP-1) was observed in the
      colon of animals treated with ADMSC. We also observed a significant reduction in
      the frequencies of macrophages (F4/80+CD11b+) and dendritic cells (CD11c+CD103+)
      in the intestinal lamina propria of ADMSC-treated mice. Finally, we detected the
      up-regulation of immunoregulatory-associated molecules in intestine of mice
      treated with ADMSCs (i.e., elevated arginase-1 and IL-10). Thus, this present
      study demonstrated that ADMSC modulates the overall gut inflammation (cell
      activation and recruitment) in experimental colitis, providing support to the
      further development of new strategies in the treatment of intestinal diseases.

PMID- 29063490
TI  - Effect of somatosensory and neurofeedback training on balance in older healthy
      adults: a preliminary investigation.
AB  - The aim of this study was to assess the effectiveness of balance training with
      somatosensory and neurofeedback training on dynamic and static balance in
      healthy, elderly adults. The sample group consisted of 45 healthy adults randomly
      assigned to one of the three test groups: somatosensory, neurofeedback, and a
      control. Individualization of the balance program started with pre-tests for
      static and dynamic balances. Each group had 15- and 30-min training sessions. All
      groups were tested for static (postural stability) and dynamic balances (Berg
      Balance Scale) in acquisition and transfer tests (fall risk of stability and
      timed up and go). Improvements in static and dynamic balances were assessed by
      somatosensory and neurofeedback groups and then compared with the control group.
      Results indicated significant improvements in static and dynamic balances in both
      test groups in the acquisition test. Results revealed a significant improvement
      in the transfer test in the neurofeedback and somatosensory groups, in static and
      dynamic conditions, respectively. The findings suggest that these methods of
      balance training had a significant influence on balance. Both the methods are
      appropriate to prevent falling in adults. Neurofeedback training helped the
      participants to learn static balance, while somatosensory training was effective
      on dynamic balance learning. Further research is needed to assess the effects of
      longer and discontinuous stimulation with somatosensory and neurofeedback
      training on balance in elderly adults.

PMID- 29063493
TI  - Chronic Disease Model of Shared Care after Obesity and Metabolic Surgery.

PMID- 29063491
TI  - A possible correlation between the basal ganglia motor function and the inverse
      kinematics calculation.
AB  - The main hypothesis of this study, based on experimental data showing the
      relations between the BG activities and kinematic variables, is that BG are
      involved in computing inverse kinematics (IK) as a part of planning and decision
      making. Indeed, it is assumed that based on the desired kinematic variables (such
      as velocity) of a limb in the workspace, angular kinematic variables in the joint
      configuration space are calculated. Therefore, in this paper, a system-level
      computational model of BG is proposed based on geometrical rules, which is able
      to compute IK. Next, the functionality of each part in the presented model is
      interpreted as a function of a nucleus or a pathway of BG. Moreover, to overcome
      existing redundancy in possible trajectories, an optimization problem minimizing
      energy consumption is defined and solved to select an optimal movement trajectory
      among an infinite number of possible ones. The validity of the model is checked
      by simulating it to control a three-segment manipulator with rotational joints in
      a plane. The performance of the model is studied for different types of movement
      including different reaching movements, a continuous circular movement and a
      sequence of tracking movements. Furthermore, to demonstrate the physiological
      similarity of the presented model to the BG structure, the neuronal activity of
      each part of the model considered as a BG nucleus is verified. Some changes in
      model parameters, inspired by the dopamine deficiency, also allow simulating some
      symptoms of Parkinson's disease such as bradykinesia and akinesia.

PMID- 29063496
TI  - Kocuria massiliensis sp. nov, a new bacterial species isolated from a patient
      with foot osteomyelitis.
AB  - Most of the species from the genus Kocuria are environmental or commensals of
      mammalian skin and oral bacteria, and had rarely been associated with human
      infection. However, recent reports showed an increase of the clinical role of
      these bacteria in human infectious diseases. Most of the cases occurred in
      hospitals and were device related. They included bacteremia, peritonitis,
      abscess, endocarditis and ocular infection. We here describe the main
      characteristics and the draft genome of Kocuria massiliensis sp. nov., strain
      P3598T (CSURP3598), a new Kocuria species that caused foot osteomyelitis in a 78
      year-old woman. The improvement of diagnostic tools for the identification of
      bacteria in microbiological laboratories, including MALDI-TOF MS and 16S rRNA
      sequencing, largely contributed to the emergence and to the expansion of the
      clinical spectrum of infections caused by Kocuria spp. To the best of our
      knowledge, we report here the first case of osteomyelitis with a bacterial
      species from the genus Kocuria.

PMID- 29063494
TI  - Bariatric Embolization of the Left Gastric Arteries for the Treatment of Obesity:
      9-Month Data in 5 Patients.
AB  - PURPOSE: The purpose of this study is to investigate the safety and 9-month
      effectiveness of transcatheter left gastric artery embolization (LGAE) for
      treating patients with obesity. MATERIALS AND METHODS: The protocol of this study
      was approved by the Institutional Ethics Review Board. Five obese patients (3 men
      and 2 women) with mean weight of 102.0 +/- 16.19 kg (range, 82.1-125.5 kg) and
      mean body mass index (BMI) of 38.1 kg/m2 +/- 3.8 (range, 32.9-42.4 kg/m2)
      underwent LGAE with polyvinyl alcohol (PVA) particles in diameter of 500-710 MUm.
      The primary endpoint was the safety by grading the adverse events (AEs) according
      to the Common Terminology Criteria for Adverse Events (CTCAE v4.0) within 30 days
      after LGAE. The secondary endpoints were measured with serum ghrelin and leptin
      levels, body weight, waist circumference, waist-to-height ratio, and abdominal
      fat quantity on MRI at the day immediately before LGAE and every 3 months after
      LGAE. RESULTS: LGAE was successfully performed in all patients. A superficial
      linear ulceration below the cardia was seen in 1 patient 3 days after LGAE and
      healed within 30 days. No other serious AEs (grade III or above) occurred.
      Average body weight loss at 3, 6, and 9 months was 8.28 +/- 7.3 kg (p = 0.074),
      10.42 +/- 8.21 kg (p = 0.047), and 12.9 +/- 14.66 kg (p = 0.121), respectively.
      The level of serum ghrelin decreased by 40.83% (p = 0.009), 31.94% (p = 0.107),
      and 24.82% (p = 0.151) at 3, 6, and 9 months after LGAE, respectively. There was
      minimal reduction of leptin levels at 3 and 6 months following LGAE (decreased by
      0.26%, p = 0.929, and 4.33%, p = 0.427, respectively), but it declined obviously
      9 months after LGAE (decreased by 11.22%, p = 0.295). Both waist circumference
      and waist-to-height ratio decreased after LGAE. MRI showed the area of
      subcutaneous adipose tissue decreased from the baseline of 400.90 +/- 79.25 to
      320.36 +/- 68.06 cm2 (decreased by 20.09%, p = 0.006) at 3 months, to 328.31 +/-
      52.67 cm2 (decreased by 18.11%, p = 0.020) at 6 months, and to 286.40 +/- 55.72
      cm2 (decreased by 28.52%, p = 0.101) at 9 months after LGAE, respectively. But
      the decrease of abdominal fat loss at 9 months after LGAE was largely due to the
      reduction in visceral adipose tissue. CONCLUSIONS: Our study with 9-month data in
      5 patients indicates that bariatric embolization of the LGA is a safe and may be
      a promising strategy to suppress the production of ghrelin and results in weight
      loss and abdominal fat reduction. TRIAL REGISTRATION: ClinicalTrials.gov
      (NCT02786108).

PMID- 29063495
TI  - Calcitonin-Producing Neuroendocrine Neoplasms of the Pancreas:
      Clinicopathological Study of 25 Cases and Review of the Literature.
AB  - Increased levels of circulating calcitonin are a clue in the diagnosis of
      medullary thyroid carcinoma. However, hypercalcitoninemia can also be related to
      other pathological conditions, including pancreatic neuroendocrine neoplasms
      (PanNENs). Ectopic hormonal production is not unusual in both functioning and non
      functioning PanNENs; however, little is known about the frequency of calcitonin
      expression in these neoplasms. The aims of this study were to assess the
      frequency of calcitonin immunoreactivity in PanNENs, independently from serum
      calcitonin levels, and to evaluate the clinicopathological and prognostic
      features of calcitonin-immunoreactive (Cal-IR) PanNENs, including a comparison
      with cases already reported in the literature. We screened 229 PanNENs for the
      immunohistochemical expression of calcitonin, including both functioning and non
      functioning neoplasms, as well as both well-differentiated and poorly
      differentiated PanNENs. Both the clinicopathological data and the follow-up
      information were available and were compared with the immunohistochemical
      results. In addition, we reviewed the features of the calcitonin-producing
      PanNENs previously reported in the literature. Calcitonin was expressed in 25 of
      our 229 PanNENs (10.9%). Examples of well- and poorly differentiated, as well as
      both functioning and non-functioning PanNENs, were found to be calcitonin
      immunoreactive. Cal-IR PanNENs did not show any significant difference with the
      whole series of neoplasms included in the study, when the clinicopathological
      parameters were considered, except for a younger age at diagnosis and for a
      larger size of the tumor in non-functioning Cal-IR PanNENs. Taken together, our
      results show that calcitonin immunoreactivity is not an exceptional event in
      PanNENs. Furthermore, calcitonin expression does not identify a separate clinical
      entity, in contrast to other PanNENs with ectopic hormone production, such as
      adrenocorticotropic hormone (ACTH)-producing PanNENs, which show a distinctively
      more aggressive behavior.

PMID- 29063497
TI  - Coping and adjustment in men with prostate cancer: a systematic review of
      qualitative studies.
AB  - PURPOSE: Prostate cancer (PCa) is one of the most common forms of cancer amongst
      males. Men's coping responses are an important determinant of functioning and
      adjustment to this disease. Previous qualitative research exists in this area,
      but the current review sought to systematically review and summarise these
      studies. METHODS: A systematic review was conducted to identify studies concerned
      with men's coping strategies in their attempts to live with PCa. A search of
      relevant electronic databases was conducted to identify studies that met
      inclusion criteria for this review. Methodological quality assessment was also
      undertaken for each included study. RESULTS: One hundred twenty-one publications
      were identified for initial screening, and 18 studies were included in the
      review. A total of five coping strategy categories or 'meta-themes' were
      identified across included studies. These categories were labelled 'avoidance,
      minimisation, and withdrawal', 'directing cognition and attention', 'reframing
      masculinity and seeking support', 'retain pre-illness identity and lifestyle',
      and 'symptom/side-effect management'. CONCLUSIONS: A range of coping strategies
      were reported by men with PCa. Some of these strategies appear to be partially
      influenced by gender roles and masculinities. Coping meta-themes reported in this
      review have also been found in other research on men's coping. Strategies
      relating to flexible interpretation of gender roles/masculinities may be a
      particularly relevant category of coping responses due to the hypothesised
      beneficial impact of flexibility on psychological well-being. IMPLICATIONS FOR
      CANCER SURVIVORS: PCa survivors utilise a range of coping strategies, and the
      types of strategies used may have implications for men's well-being. The ability
      to be flexible in both coping responses used, and in the view of oneself as a man
      may be particularly important skills in meeting the challenges associated with
      this disease.

PMID- 29063498
TI  - Inhibiting influenza virus replication and inducing protection against lethal
      influenza virus challenge through chitosan nanoparticles loaded by siRNA.
AB  - Influenza virus causes a highly contagious viral respiratory tract infection with
      potentially fatal outcomes in humans and animals. There is now widespread
      influenza virus resistance to commercial drugs due to the genetic diversity of
      virus. Therefore, new therapeutic formulation needs to be developed.
      Chitosan/siRNA nanoparticles were generated as a new therapeutic approach against
      influenza virus infections both in vitro and in vivo. Designed siRNA against
      influenza nucleoprotein was formulated in chitosan polymer as siRNA/chitosan
      nanoparticle complex. Particle size and zeta potential of the nanoparticles were
      measured by dynamic light scattering. The uptake of labeled siRNA into Vero cells
      was visualized using fluorescence microscopy. Nanoparticle-mediated knockdown of
      enhanced green fluorescent protein (EGFP) was analyzed and quantified by flow
      cytometry in Vero cells. Results of the in vitro study showed that chitosan/siRNA
      nanoparticle was efficiently uptaken by Vero cells, leading to inhibition of
      influenza virus replication. Furthermore, nasal delivery of siRNA by chitosan
      nanoparticle complex has antiviral effects and significantly protected BALB/c
      mice from a lethal influenza challenge. These findings suggest that chitosan
      nanoparticle equipped with siRNA is a promising system for controlling influenza
      virus infection.

PMID- 29063499
TI  - At the dawn of personalized reproductive medicine: opportunities and challenges
      with incorporating multigene panel testing into fertility care.

PMID- 29063500
TI  - A case of chimerism-induced paternity confusion: what ART practitioners can do to
      prevent future calamity for families.
AB  - In the fertility clinic setting, a negative DNA paternity test result usually
      suggests a sample mix-up likely occurred at the testing company or in the clinic.
      However, we report a case where, despite repeat negative paternity test results,
      the alleged father (referred to as "the proband") was confirmed to be the baby's
      father. The proband, a 34 year-old male, contacted our research group when
      routine blood testing revealed discrepant blood types between the parents and the
      baby, repeat paternity tests were negative (excluding the proband as the baby's
      father), and the fertility clinic found no evidence of any wrongdoing. Microarray
      technology was utilized to confirm biological relatedness, which revealed an
      avuncular (uncle/nephew) relationship. Additional tissue samples were analyzed
      and family studies were conducted at paternity and forensic laboratories using
      STR-based DNA tests to elucidate the proband's condition of congenital
      tetragametic chimerism. His paternity was subsequently affirmed and the fertility
      clinic exonerated of claims of a semen sample mix-up. This case underscores the
      possibility that some allegations of fertility clinic missteps may be explained
      by undiagnosed chimerism, a condition where an individual harbors two distinct
      genomes. We offer specific suggestions for improving laboratory reporting and
      creating clinical guidelines to aid in identifying and rectifying future cases of
      false exclusions of paternity due to chimerism.

PMID- 29063503
TI  - Are blastocyst aneuploidy rates different between fertile and infertile
      populations?
AB  - PURPOSE: This study aimed to determine if patients with infertility or recurrent
      pregnancy loss have higher rates of embryo aneuploidy than fertile controls.
      METHODS: This was a retrospective review of all pre-implantation genetic
      screening (PGS) cases processed by a single reference lab prior to March 2014
      after a blastocyst biopsy. Cases were excluded if no indication for PGS was
      designated or patients were translocation carriers. The fertile control group
      consisted of patients undergoing IVF with PGS for sex selection only. The
      comparison cohorts included those with recurrent pregnancy loss, male factor
      infertility, unexplained infertility, prior failed IVF, or previous aneuploid
      conceptions. A quasi-binomial regression model was used to assess the
      relationship between the dependent variable, aneuploidy rate and the independent
      variables, maternal age and reason for PGS. A quasi-Poisson regression model was
      used to evaluate the relationship between similar independent variables and the
      number of blastocyst biopsies per case. RESULTS: The initial study population
      consisted of 3378 IVF-PGS cycles and 18,387 analyzed trophectoderm samples.
      Controlling for maternal age, we observed an increased rate of aneuploidy among
      patients with recurrent pregnancy loss (OR 1.330, p < 0.001), prior aneuploid
      pregnancy (OR 1.439, p < 0.001), or previous failed IVF cycles (OR 1.356, p =
      0.0012) compared to fertile controls. Patients with unexplained and male factor
      infertility did not have a significantly different aneuploidy rate than controls
      (p > 0.05). The increase in aneuploidy in patients with RPL and prior IVF failure
      was driven by both an increase in meiotic (OR 1.488 and 1.508, p < 0.05) and
      mitotic errors (1.269 and 1.393, p < 0.05) relative to fertile controls, while
      patients with prior aneuploid pregnancies had only an increased risk of meiotic
      error aneuploidies (OR 1.650, p < 0.05). CONCLUSIONS: Patients with recurrent
      pregnancy loss, previous IVF failures, and prior aneuploid pregnancies have a
      significantly higher, age-independent, aneuploidy rate compared to patients
      without infertility.

PMID- 29063504
TI  - Abnormal interaction between cognitive control network and affective network in
      patients with end-stage renal disease.
AB  - End-stage renal disease (ESRD) is a common complicated disorder that is generally
      associated with an altered central nervous system and cognitive impairment.
      Neuroimaging studies have recorded aberrant brain circuits in patients with ESRD
      that were closely associated with abnormal clinical manifestations. However,
      whether the altered interaction was within and/or between these circuits is
      largely unclear. We investigated brain topological organization and/or module
      interaction by employing resting-state functional magnetic resonance imaging (rs
      fMRI) and modularity network analysis in 24 patients with ESRD and 20 age- and
      gender-matched healthy control (HC) subjects. Stroop task was used to evaluate
      the performance of cognitive control in all subjects. At the global level, ESRD
      patients exhibited significantly decreased global and local efficiency which were
      mainly related to abnormal functional connectivity of the amygdala and inferior
      frontal gyrus (IFG). Stepwise regression analysis was applied to estimate the
      relationships between network efficiency and blood biochemistry level (urea,
      creatine, phosphate, Ca2+, hematocrit, cystatin, hemoglobin levels, parathyroid
      hormone, K+ and Na+), and only the hematocrit level was significantly associated
      with global efficiency in patients with ESRD. At the modular level, we discovered
      an aberrant brain interaction between the amygdala- and IFG-related circuits in
      the ESRD group, and the regional efficiency of the amygdala was observably
      relative to the performance of cognitive control in patients with ESRD. Our
      results suggested that ESRD exhibited aberrant brain functional topological
      organization and module-level interaction between the affective and cognitive
      control circuits, providing crucial insights into the pathophysiological
      mechanism of ESRD patients.

PMID- 29063501
TI  - The normality of sperm in an infertile man with ring chromosome 15: a case
      report.
AB  - PURPOSE: The purpose of this report is to analyze the chromosome status and
      fertilization capability of sperm obtained from an infertile male patient with
      ring chromosome 15. METHODS: This was a case report at a private in vitro
      fertilization clinic. A man diagnosed with severe oligozoospermia carrying ring
      chromosome 15. To evaluate the chromosome status and fertilization capability,
      sperm from a patient carrying ring chromosome 15 were injected into enucleated
      mouse oocytes. RESULTS: The karyotypes of motile sperm from a patient carrying
      ring chromosome 15 were normal, and ring chromosome 15 was not observed in the
      chromosome spread samples of 1PN. In addition, these motile sperm retained the
      fertilization capability. However, the fertilization rates decreased (85.2, 76.2,
      and 64.3%, respectively) along with the decline of the aspect ratio of the sperm
      head (>= 1.50, 1.30-1.49, and < 1.30, respectively). CONCLUSIONS: The karyotypes
      were normal without ring chromosome 15, and motile sperm with a high aspect ratio
      showed adequate potential for fertilization.

PMID- 29063502
TI  - Arabian Peninsula ethnicity is associated with lower ovarian reserve and ovarian
      response in women undergoing fresh ICSI cycles.
AB  - PURPOSE: Recent studies have demonstrated that ethnicity can be an independent
      determinant of assisted reproductive technology (ART) outcomes. In this context,
      we investigate whether ART outcomes differ between Arabian Peninsula and
      Caucasian women. METHODS: This is a retrospective cohort study of women
      undergoing fresh intracytoplasmic sperm injection (ICSI)-embryo transfer (ET)
      cycles for male factor infertility. The study cohort was divided into 2 groups
      based on ethnicity-Arabian Peninsula or Caucasian. Ovarian reserve, ovarian
      response, and pregnancy outcomes were compared between the groups. A sub-analysis
      was performed between individual Arabian Peninsula nationalities for the same
      outcomes. A multiple linear regression model was used to assess the independent
      effect of ethnicity on ovarian response. RESULTS: Seven hundred sixty-three
      patients were included-217 (28.4%) Arabian Peninsula and 546 (71.6%) Caucasian.
      There was no difference in the mean age of the two groups; however, the former
      had a higher body mass index (28.5 +/- 7.5 vs. 23.3 +/- 5.7; P < 0.001). Although
      follicle stimulating hormone (FSH) levels and antral follicle counts (AFC) were
      within the normal range in both groups, Arabian Peninsula women had higher FSH
      levels (5.7 +/- 2.5 vs. 4.9 +/- 2.8; P = 0.001) and lower AFC (13.9 +/- 4.7 vs.
      16.5 +/- 4.3; P < 0.001) when compared to Caucasian women. Women from the Arabian
      Peninsula also had a statistically lower number of mature oocytes retrieved (15.6
      +/- 6.8 vs. 14.1 +/- 8.4; P = 0.01), despite requiring higher gonadotropin doses.
      Multiple linear regression reveled that Arabian Peninsula women had 2.5 (95% CI
      2.1-3.9) less mature oocytes, even after controlling for confounders. A sub
      analysis within the Arab cohort demonstrated that Qatari women had a higher yield
      of mature oocytes when compared to Emirati, Kuwaiti, and Saudi women. There was
      no difference in the rates of implantation, clinical pregnancy, or live birth
      when comparing individual Arabian Peninsula nationalities with each other or to
      Caucasians. CONCLUSIONS: Arabian Peninsula ethnicity is associated with lower
      ovarian reserve and ovarian response parameters in women undergoing their first
      ICSI-ET cycle.

PMID- 29063505
TI  - Control beliefs are associated with preserved memory function in the face of low
      hippocampal volume among diverse older adults.
AB  - Growing evidence supports a link between locus of control and memory in older
      adults. Control beliefs may directly predict larger hippocampal volume (i.e.,
      brain maintenance). Alternatively, control beliefs may be associated with smaller
      hippocampal volume at any given level of memory (i.e., cognitive reserve).
      Multivariable regression analyses examined associations between verbal episodic
      memory, locus of control and hippocampal volume among 236 non-demented older
      adults in the community-based Washington Heights-Inwood Columbia Aging Project.
      Control beliefs were negatively associated with hippocampal volume when
      controlling for memory performance, indicating that individuals with stronger
      control beliefs were able to maintain memory function in the face of lower
      hippocampal volume. Subsequent exploratory models stratified by race/ethnicity
      indicated that this association was more prominent among racial/ethnic minorities
      (particularly Caribbean Hispanic older adults) than among non-Hispanic White
      older adults. Control beliefs were not associated with hippocampal volume before
      memory was taken into account. Results are consistent with the view that control
      beliefs facilitate the maintenance of memory function despite hippocampal volume
      loss. Results are not consistent with the view that locus of control contributes
      to brain maintenance. Culturally-appropriate interventions are needed to test
      whether strengthening control beliefs provides cognitive resistance to
      neuropathology.

PMID- 29063507
TI  - Awareness and Knowledge Levels of 18-Year-Old and Older Individuals Regarding
      Human Papillomavirus (HPV) and HPV Vaccine in Hatay, Turkey.
AB  - The aim of this study was to evaluate the knowledge and awareness levels of 18
      year-old and older women and men on HPV infection, HPV vaccine, and the potential
      risk factors in Hatay, Turkey. In our study, it was found that overall 27.0 and
      23.2% of the participants reported having heard of HPV infection and HPV vaccine.
      The rate of participants who had heard of HPV infection and HPV vaccine was
      higher in women than in men (p < 0.000). Thirteen percent of the participants was
      aware of the fact that HPV triggers cervical cancer, 10.2% penile cancer, and
      16.7% genital warts, respectively. The overall vaccination rate of the
      participants was 2.7%. When the total knowledge score of the participants about
      HPV infection and HPV vaccine was evaluated according to independent variables,
      it was found that being a woman, urbanization, and having a high level of
      education had a positive effect on knowledge score, while never having heard of
      HPV infection and HPV vaccine had a negative effect on knowledge score (p <
      0.000). It was determined in the linear regression model that gender, educational
      status, residential area, and having heard of HPV infection before influenced
      knowledge levels. It was determined that the relation between these variables and
      the total knowledge scores of the participants was statistically significant (p <
      0.05). It was also determined that women who had higher educational levels, those
      who were living in urban areas, and those who had heard HPV infection before had
      higher knowledge levels. The level of knowledge of the participants about HPV
      infection and HPV vaccine was found to be very low. Having adequate knowledge
      about HPV infection and increasing the acceptance of HPV vaccination in public
      will play an important role in decreasing the rate of mortality and morbidity of
      the different HPV-associated cancers in women and men.

PMID- 29063506
TI  - Opportunities for an enhanced integration of neuroscience and genomics.
AB  - Neuroimaging and genetics are two rapidly expanding fields of research.
      Thoughtful integration of these areas is critical for ongoing large-scale
      research into the genetic mechanisms underlying brain structure, function, and
      development. Neuroimaging genetics has been slow to evolve relative to
      psychiatric genetics research, and some may be unaware that new statistical
      methods allow for the genomic analysis of more modestly-sized imaging samples. We
      present a broad overview of the extant imaging genetics literature, provide an
      interpretation of the major problems surrounding the integration of neuroimaging
      and genetics, discuss the influence and impact of genetics consortia, and suggest
      statistical genetic analyses that expand the repertoire of imaging researchers
      amassing rich behavioral data in modestly-sized samples. Specific attention is
      paid to the creative use of polygenic risk scoring in imaging genetic analyses,
      with primers on the most current risk scoring applications.

PMID- 29063508
TI  - Age-related changes in cyclic phosphatidic acid-induced hyaluronic acid synthesis
      in human fibroblasts.
AB  - Hyaluronic acid is a major component of the extracellular matrix, which is
      important for skin hydration. As aging brings skin dehydration, we aimed to
      clarify the mRNA expression of hyaluronic acid-related proteins in human skin
      fibroblasts from donors of various ages (range 0.7-69 years). Previously, we
      reported that cyclic phosphatidic acid (cPA), a unique phospholipid mediator,
      stimulated the expression of HAS2 and increased hyaluronic acid synthesis in
      human skin fibroblasts (donor age: 3 days). In this study, we measured the mRNA
      expression of hyaluronic acid-related proteins: hyaluronan synthase (HAS) 1-3,
      hyaluronidase-1, -2, and hyaluronic acid-binding protein (versican). In addition,
      we tested whether cPA could increase hyaluronic acid synthesis in skin
      fibroblasts derived from donors of various ages. The expression of HAS1, 3,
      hyaluronidase-1, and -2 did not change with aging. However, the mRNA expression
      of versican decreased with aging. Although it is thought that the amount of
      hyaluronic acid in the dermis decreases with aging, the mRNA expression of HAS2
      was increased. But the amount of hyaluronic acid secreted by fibroblasts did not
      increase with aging. This suggests that the activity and/or protein expression of
      HAS2 decrease with aging. Furthermore, we observed that cPA caused the increase
      of hyaluronic acid synthesis at any age, and this effect was increased with
      aging. These results suggest that aging made the fibroblasts more sensitive to
      cPA treatment. Therefore, cPA represents a suitable candidate for the health
      maintenance and improvement of the skin by increasing the level of hyaluronic
      acid in the dermis.

PMID- 29063509
TI  - Erratum to: Efficacy of Additional Canagliflozin Administration to Type 2
      Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic
      Patterns Using Continuous Glucose Monitoring (CGM).
AB  - Unfortunately, the original publication of this paper contained errors in the
      presentation of Fig. 2.

PMID- 29063510
TI  - Timing of Insulin Injections, Adherence, and Glycemic Control in a Multinational
      Sample of People with Type 2 Diabetes: A Cross-Sectional Analysis.
AB  - INTRODUCTION: We investigated the association of bolus insulin dose timing with
      demographics, adherence, diabetes education program participation, experience
      with hypoglycemic events, glycemic control, and patient preference among
      respondents with type 2 diabetes. METHODS: Adults with type 2 diabetes from 12
      countries were recruited to a Web-based self-reported patient preference survey.
      Adherence was measured using an adapted Morisky Medication Adherence Scale
      questionnaire. RESULTS: In total 1483 respondents reported using bolus insulin
      with 58% (n = 864) dosing bolus insulin before meals (pre-meal cohort), 354 (24%)
      during or after meals (post-meal cohort), and 265 (18%) before, during, or after
      meals (mixed cohort). The mixed cohort was excluded, thus 1218 respondents were
      included in the analysis. Respondent distribution across HbA1c category differed
      significantly depending on insulin dose timing (p = 0.0006); more respondents in
      the post-meal cohort (40%) had HbA1c >= 9% (74.9 mmol/mol) than in the pre-meal
      cohort (29%). The post-meal cohort was significantly more likely to report non
      adherence than the pre-meal cohort (OR = 1.50, p = 0.01) and significantly more
      often reported participating in diabetes education programs (p < 0.05). Seventy
      eight percent of all respondents reported preferring bolus insulin administrable
      whenever convenient. CONCLUSIONS: Approximately 24% of respondents never comply
      with guidelines for insulin dose timing, with higher risk of non-adherence and
      increased participation in diabetes care programs. Respondents dosing insulin
      post-meal are more likely to have poor glycemic control (HbA1c >= 9%, 74.9
      mmol/mol). Given that many respondents had high HbA1c and were non-adherent, a
      treatment which satisfies patient preference for bolus insulin with flexible dose
      timing could be considered. FUNDING: Novo Nordisk.

PMID- 29063511
TI  - Cost-Effectiveness of IDegLira Versus Insulin Intensification Regimens for the
      Treatment of Adults with Type 2 Diabetes in the Czech Republic.
AB  - INTRODUCTION: The aim of this study was to evaluate the long-term cost
      effectiveness of the insulin degludec/liraglutide combination (IDegLira) versus
      basal insulin intensification strategies for patients with type 2 diabetes
      mellitus (T2DM) not optimally controlled on basal insulin in the Czech Republic.
      METHODS: Cost-effectiveness was evaluated using the QuintilesIMS Health CORE
      Diabetes model, an interactive internet-based model that simulates clinical
      outcomes and costs for cohorts of patients with diabetes. The analysis was
      conducted from the perspective of the Czech Republic public payer. Sensitivity
      analyses were conducted to explore the sensitivity of the model to plausible
      variations in key parameters. RESULTS: The use of IDegLira was associated with an
      improvement in the quality-adjusted life expectancy of 0.31 quality-adjusted life
      years (QALYs), at an additional cost of Czech Koruna (CZK) 107,829 over a
      patient's lifetime compared with basal-bolus therapy, generating an incremental
      cost-effectiveness ratio (ICER) of CZK 345,052 per QALY gained. In a scenario
      analysis, IDegLira was associated with an ICER of CZK 693,763 per QALY gained
      compared to basal insulin + glucagon-like peptide-1 receptor agonist (GLP-1 RA).
      The ICERs are below the generally accepted willingness-to-pay threshold (CZK
      1,100,000/QALY gained at the time of this analysis). CONCLUSIONS: Results from
      this evaluation suggest that IDegLira is a cost-effective treatment option
      compared with basal-bolus therapy and basal insulin + GLP-1 RA for patients with
      T2DM in the Czech Republic whose diabetes is not optimally controlled with basal
      insulin. FUNDING: Novo Nordisk.

PMID- 29063512
TI  - Brain-specific HIV Nef identified in multiple patients with neurological disease.
AB  - HIV-1 Nef is a flexible, multifunctional protein with several cellular targets
      that is required for pathogenicity of the virus. This protein maintains a high
      degree of genetic variation among intra- and inter-host isolates. HIV Nef is
      relevant to HIV-associated neurological diseases (HAND) in patients treated with
      combined antiretroviral therapy because of the protein's role in promoting
      survival and migration of infected brain macrophages. In this study, we analyzed
      2020 HIV Nef sequences derived from 22 different tissues and 31 subjects using a
      novel computational approach. This approach combines statistical regression and
      evolved neural networks (ENNs) to classify brain sequences based on the physical
      and chemical characteristics of functional Nef domains. Based on training,
      testing, and validation data, the method successfully classified brain Nef
      sequences at 84.5% and provided informative features for further examination.
      These included physicochemical features associated with the Src-homology-3
      binding domain, the Nef loop (including the AP-2 Binding region), and a cytokine
      binding domain. Non-brain sequences from patients with HIV-associated
      neurological disease were frequently classified as brain, suggesting that the
      approach could indicate neurological risk using blood-derived virus or for the
      development of biomarkers for use in assay systems aimed at drug efficacy studies
      for the treatment of HIV-associated neurological diseases.

PMID- 29063513
TI  - Variability in C-reactive protein is associated with cognitive impairment in
      women living with and without HIV: a longitudinal study.
AB  - Despite the availability of effective antiretroviral therapies, cognitive
      impairment (CI) remains prevalent in HIV-infected (HIV+) individuals. Evidence
      from primarily cross-sectional studies, in predominantly male samples, implicates
      monocyte- and macrophage-driven inflammatory processes linked to HIV-associated
      CI. Thus, peripheral systemic inflammatory markers may be clinically useful
      biomarkers in tracking HIV-associated CI. Given sex differences in immune
      function, we focused here on whether mean and intra-individual variability in
      inflammatory marker-predicted CI in HIV+ and HIV- women. Seventy-two HIV+ (36
      with CI) and 58 HIV- (29 with CI) propensity-matched women participating in the
      Women's Interagency HIV Study completed a neuropsychological battery once between
      2009 and 2011, and performance was used to determine CI status. Analysis of 13
      peripheral immune markers was conducted on stored biospecimens at three time
      points (7 and 3.5 years before neuropsychological data collection and concurrent
      with data collection). HIV+ women showed alterations in 8 immune markers compared
      to HIV- women. The strongest predictors of CI across HIV+ and HIV- women were
      lower mean soluble tumor necrosis factor receptor I (sTNFRI) levels, higher mean
      interleukin (IL)-6 levels, and greater variability in C-reactive protein (CRP)
      and matrix metalloproteinase (MMP)-9 (p values < 0.05). Stratified by HIV, the
      only significant predictor of CI was greater variability in CRP for both HIV+ and
      HIV- women (p values < 0.05). This variability predicted lower executive
      function, attention/working memory, and psychomotor speed in HIV+ but only
      learning in HIV- women (p values < 0.05). Intra-individual variability in CRP
      levels over time may be a good predictor of CI in predominately minority low
      socioeconomic status midlife women.

PMID- 29063515
TI  - Zika virus induces astrocyte differentiation in neural stem cells.
AB  - Zika virus (ZIKV) is a rapidly emerging flavivirus that has been associated with
      a number of congenital neurological manifestations. Here, we show that ZIKV
      replicated efficiently in mouse neural stem cells (mNSCs). ZIKV infection caused
      a cytopathic effect without affecting cell viability, yet led to a significant
      decrease in the number of proteins secreted into mNSC supernatants. A gene
      expression array of neural stem cell progenitor and differentiation markers
      suggested that infection reduced the number of neuronal and oligodendrocyte
      progenitors while increasing the number of astrocyte progenitors. Infection in
      astrocytes increased transcription of key genes involved in the antiviral
      response. These data provide molecular and cellular evidence that ZIKV
      significantly alters neural development in the vertebrate host and that astrocyte
      differentiation may be a protective response that limits neuropathogenesis.

PMID- 29063514
TI  - Biomarkers of neuronal injury and amyloid metabolism in the cerebrospinal fluid
      of patients infected with HIV-1 subtypes B and C.
AB  - Based on prior reports that the HIV-1 Tat protein modulates amyloid-beta (Abeta)
      metabolism, this study aimed to compare CSF neural injury biomarkers between 27
      patients with HIV subtype B, 26 patients with HIV subtype C, 18 healthy HIV
      negative controls, and 24 patients with Alzheimer's disease (AD). Immunoassays
      were used to measure soluble amyloid precursor protein alpha and beta (sAPPalpha,
      sAPPbeta), Abeta oligomers 38, 40, 42, and Abeta-total; phosphorylated tau (P
      tau181), and total tau (T-tau). Comparisons between HIV(+) and HIV(-) (including
      AD) were adjusted by linear regression for gender and age; HIV subtype
      comparisons were adjusted for nadir CD4 and plasma viral load suppression. The p
      values were corrected for multiple testing with the Benjamini-Hochberg procedure.
      CSF Abeta-42 and Hulstaert (P-tau181) index were lower in HIV1-C than B (p =
      0.03, and 0.049 respectively); subtypes did not differ on other CSF biomarkers or
      ratios. Compared to AD, HIV(+) had lower CSF levels of T-tau, P-tau181 (p <
      0.001), and sAPPalpha (p = 0.041); HIV(+) had higher CSF Abeta-42 (p = 0.002) and
      higher CSF indexes: [Abeta-42/(240 + 1.18 T-tau)], P-tau181/Abeta-42, T-tau/Abeta
      42, P-tau181/T-tau, sAPPalpha/beta (all p <= 0.01) than AD. Compared to HIV(-),
      HIV(+) had lower CSF Abeta-42, and T-tau (all p <= 0.004). As conclusion, amyloid
      metabolism was influenced by HIV infection in a subtype-dependent manner. Abeta
      42 levels were lower in HIV1-C than B, suggesting that there may be greater
      deposition of Abeta-42 in HIV1-C. These findings are supported by CSF Hulstaert
      (P-tau181) index. Differences between HIV and AD in the patterns of Abeta and Tau
      biomarkers suggest that CNS HIV infection and AD may not share some of same
      mechanisms of neuronal injury.

PMID- 29063516
TI  - Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment:
      results from a double-blind, placebo-controlled trial.
AB  - Paroxetine and fluconazole have neuroprotective effects in an in vitro model of
      HIV protein-mediated neuronal injury. This study evaluated the safety,
      tolerability, and efficacy of both paroxetine and fluconazole for the treatment
      of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double
      blind, placebo-controlled 2 * 2 factorial design study was used. HIV+ individuals
      with cognitive impairment were enrolled in the 24-week trial. Participants were
      randomly assigned to one of four groups: (1) paroxetine 20 mg/day, (2)
      fluconazole 100 mg every 12 h, (3) paroxetine and fluconazole, or (4) placebo.
      Safety, tolerability, and efficacy were evaluated. Forty-five HIV+ individuals
      were enrolled. Medications were well tolerated. Compared to no paroxetine arms,
      HIV+ individuals receiving paroxetine showed improved NPZ8 summary scores, (mean
      change = 0.25 vs - 0.19, p = 0.049), CalCAP sequential test reaction time (mean
      change = 0.34 vs -0.23, p = 0.014), Trail Making Part B test performance (mean
      change = 0.49 vs - 0.33, p = 0.041), and FAS verbal fluency (mean change = 0.25
      vs 0.02, p = 0.020) but a decline in the Letter number sequencing test (mean
      change = - 0.40 vs 0.26, p = 0.023). Biomarkers of cellular stress, inflammation,
      and neuronal damage were not affected by paroxetine. HIV+ individuals receiving
      fluconazole did not show a benefit in cognition and showed an increase in
      multiple markers of cellular stress compared to the no fluconazole arms. In
      conclusion, paroxetine was associated with improvement in a summary
      neuropsychological test measure and in several neuropsychological tests but worse
      performance in one neuropsychological test. Further studies of paroxetine for the
      treatment of HAND and to define its precise neuroprotective properties are
      warranted.

PMID- 29063517
TI  - PARP Inhibitors in the Treatment of Triple-Negative Breast Cancer.
AB  - Breast cancer is a heterogeneous disease, manifesting in a broad differentiation
      in phenotypes and morphologic profiles, resulting in variable clinical behavior.
      Between 10 and 20% of all breast cancers are triple negative. Triple-negative
      breast cancer (TNBC) lacks the expression of human epidermal growth factor
      receptor 2 (HER2) and hormone receptors; therefore, to date, chemotherapy remains
      the backbone of treatment. TNBC tends to be aggressive and has a high
      histological grade, resulting in a poor 5-year prognosis. It has a high
      prevalence of BRCA1 mutations and an increased Ki-67 expression. This subtype
      usually responds well to taxanes and/or platinum compounds and poly (ADP-ribose)
      polymerase (PARP) inhibitors. Studies with PARP inhibitors have demonstrated
      promising results in the treatment of BRCA-mutated breast and ovarian cancer, and
      PARP inhibitors have been studied as monotherapy and in combination with
      cytotoxic therapy or radiotherapy. PARP inhibitor efficacy on poly (ADP-ribose)
      polymer (PAR) formation in vivo can be quantified by pharmacodynamic assays that
      measure PAR activity in peripheral blood mononuclear cells (PBMC). Biomarkers
      such as TP53, ATM, PALB2 and RAD51C might be prognostic or predictive indicators
      for treatment response, and could also provide targets for novel treatment
      strategies. In summary, this review provides an overview of the treatment options
      for basal-like TNBC, including PARP inhibitors, and focuses on the
      pharmacotherapeutic options in these patients.

PMID- 29063518
TI  - Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate
      in Development for the Treatment of Alzheimer's Disease.
AB  - BACKGROUND: ALZ-801 is an orally available, valine-conjugated prodrug of
      tramiprosate. Tramiprosate, the active agent, is a small-molecule beta-amyloid
      (Abeta) anti-oligomer and aggregation inhibitor that was evaluated extensively in
      preclinical and clinical investigations for the treatment of Alzheimer's disease
      (AD). Tramiprosate has been found to inhibit beta-amyloid oligomer formation by a
      multi-ligand enveloping mechanism of action that stabilizes Abeta42 monomers,
      resulting in the inhibition of formation of oligomers and subsequent aggregation.
      Although promising as an AD treatment, tramiprosate exhibited two limiting
      deficiencies: high intersubject pharmacokinetic (PK) variability likely due to
      extensive gastrointestinal metabolism, and mild-to-moderate incidence of nausea
      and vomiting. To address these, we developed an optimized prodrug, ALZ-801, which
      retains the favorable efficacy attributes of tramiprosate while improving oral PK
      variability and gastrointestinal tolerability. In this study, we summarize the
      phase I bridging program to evaluate the safety, tolerability and PK for ALZ-801
      after single and multiple rising dose administration in healthy volunteers.
      METHODS: Randomized, placebo-controlled, phase I studies in 127 healthy male and
      female adult and elderly volunteers included [1] a single ascending dose (SAD)
      study; [2] a 14-day multiple ascending dose (MAD) study; and [3] a single-dose
      tablet food-effect study. This program was conducted with both a loose-filled
      capsule and an immediate-release tablet formulation, under both fasted and fed
      conditions. Safety and tolerability were assessed, and plasma and urine were
      collected for liquid chromatography-mass spectrometry (LC-MS) determination and
      non-compartmental PK analysis. In addition, we defined the target dose of ALZ-801
      that delivers a steady-state plasma area under the curve (AUC) exposure of
      tramiprosate equivalent to that studied in the tramiprosate phase III study.
      RESULTS: ALZ-801 was well tolerated and there were no severe or serious adverse
      events (AEs) or laboratory findings. The most common AEs were transient mild
      nausea and some instances of vomiting, which were not dose-related and showed
      development of tolerance after continued use. ALZ-801 produced dose-dependent
      maximum plasma concentration (C max) and AUC exposures of tramiprosate, which
      were equivalent to that after oral tramiprosate, but with a substantially reduced
      intersubject variability and a longer elimination half-life. Administration of
      ALZ-801 with food markedly reduced the incidence of gastrointestinal symptoms
      compared with the fasted state, without affecting plasma tramiprosate exposure.
      An immediate-release tablet formulation of ALZ-801 displayed plasma exposure and
      low variability similar to the loose-filled capsule. ALZ-801 also showed
      excellent dose-proportionality without accumulation or decrease in plasma
      exposure of tramiprosate over 14 days. Based on these data, 265 mg of ALZ-801
      twice daily was found to achieve a steady-state AUC exposure of tramiprosate
      equivalent to 150 mg twice daily of oral tramiprosate in the previous phase III
      trials. CONCLUSIONS: ALZ-801, when administered in capsule and tablet forms,
      showed excellent oral safety and tolerability in healthy adults and elderly
      volunteers, with significantly improved PK characteristics over oral
      tramiprosate. A clinical dose of ALZ-801 (265 mg twice daily) was established
      that achieves the AUC exposure of 150 mg of tramiprosate twice daily, which
      showed positive cognitive and functional improvements in apolipoprotein E4/4
      homozygous AD patients. These bridging data support the phase III development of
      ALZ-801in patients with AD.

PMID- 29063520
TI  - Individual differences in skewed financial risk-taking across the adult life
      span.
AB  - Older adults are disproportionately targeted by fraud schemes that advertise
      unlikely but large returns (positively skewed risks). We examined adult age
      differences in choice and neural activity as individuals considered risky
      gambles. Gambles were symmetric (50% chance of modest win or loss), positively
      skewed (25% chance of large gain), or negatively skewed (25% chance of large
      loss). The willingness to accept positively skewed relative to symmetric gambles
      increased with age, and this effect replicated in an independent behavioral
      study. Whole-brain functional magnetic resonance imaging analyses comparing
      positively (vs. negatively) skewed trials revealed that relative to younger
      adults, older adults showed increased anticipatory activity for negatively skewed
      gambles but reduced activity for positively skewed gambles in the anterior
      cingulate and lateral prefrontal regions. Individuals who were more biased toward
      positively skewed gambles showed increased activity in a network of regions
      including the nucleus accumbens. These results reveal age biases toward
      positively skewed gambles and age differences in corticostriatal regions during
      skewed risk-taking, and have implications for identifying financial decision
      biases across adulthood.

PMID- 29063519
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones.
AB  - Oxazolidinones are a class of synthetic antimicrobial agents with potent activity
      against a wide range of multidrug-resistant Gram-positive pathogens including
      methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.
      Oxazolidinones exhibit their antibacterial effects by inhibiting protein
      synthesis acting on the ribosomal 50S subunit of the bacteria and thus preventing
      formation of a functional 70S initiation complex. Currently, two oxazolidinones
      have been approved by the US Food and Drug Administration: linezolid and more
      recently tedizolid. Other oxazolidinones are currently under investigation in
      clinical trials. These antimicrobial agents exhibit a favourable pharmacokinetic
      profile with an excellent bioavailability and a good tissue and organ
      penetration. In-vitro susceptibility studies have shown that oxazolidinones are
      bacteriostatic against enterococci and staphylococci, and bactericidal for the
      majority of strains of streptococci. In the context of emergence of resistance to
      glycopeptides, oxazolidinones have become an effective alternative to vancomycin
      treatment frequently associated with nephrotoxicity. However, oxazolidinones, and
      linezolid in particular, are associated with significant adverse events,
      myelosuppression representing the main unfavourable side effect. More recently,
      tedizolid has been shown to effectively treat acute bacterial skin and skin
      structure infections. This newer oxazolidinone offers the advantages of once
      daily dosing and a better safety profile in healthy volunteer studies (fewer
      gastrointestinal and haematological side effects). The potential use of tedizolid
      for other infections that could require longer therapy warrants further studies
      for positioning this new oxazolidinone in the available antimicrobial
      armamentarium. Moreover, other oxazolidinones are currently under active
      investigation.

PMID- 29063521
TI  - Blunted amygdala activity is associated with depression severity in treatment
      resistant depression.
AB  - Up to 50% of individuals with major depressive disorder (MDD) do not recover
      after two antidepressant medication trials, and therefore meet the criteria for
      treatment-resistant depression (TRD). Mindfulness-based cognitive therapy (MBCT)
      is one promising treatment; however, the extent to which MBCT influences clinical
      outcomes relative to baseline neural activation remains unknown. In the present
      study we investigated baseline differences in amygdala activation between TRD
      patients and healthy controls (HCs), related amygdala activation to depression
      symptoms, and examined the impacts of MBCT and amygdala activation on
      longitudinal depression outcomes. At baseline, TRD patients (n = 80) and HCs (n =
      37) participated in a functional magnetic resonance imaging task in which they
      identified either the emotion (affect labeling) or the gender (gender labeling)
      of faces, or passively viewed faces (observing). The TRD participants then
      completed eight weeks of MBCT or a health enhancement program (HEP). Relative to
      HCs, the TRD patients demonstrated less amygdala activation during affect
      labeling, and marginally less during gender labeling. Blunted amygdala activation
      in TRD patients during affect labeling was associated with greater depression
      severity. MBCT was associated with greater depression reductions than was HEP
      directly following treatment; however, at 52 weeks the treatment effect was not
      significant, and baseline amygdala activation across the task conditions
      predicted depression severity in both groups. TRD patients have blunted amygdala
      responses during affect labeling that are associated with greater concurrent
      depression. Furthermore, although MBCT produced greater short-term improvements
      in depression than did HEP, overall baseline amygdala reactivity was predictive
      of long-term clinical outcomes in both groups.

PMID- 29063524
TI  - On the relationship between proteinuria and plasma phosphate.
AB  - Albuminuria is strongly associated with renal and cardiovascular outcomes
      independently of renal function level. However, the pathophysiology of these
      associations is debated. In chronic kidney disease (CKD), phosphate retention
      participates in cardiovascular events and increased cardiovascular mortality. We
      hypothesised that albuminuria may modulate tubular phosphate handling by the
      kidney. To verify this hypothesis, we first studied the association between
      phosphataemia and albuminuria in children with nephrotic syndrome and in adults
      with CKD. In both cases, higher albuminuria was associated with higher phosphate
      level, independently of glomerular filtration rate. We further tried to decipher
      the molecular mechanisms of these observations. Using animal models of nephrotic
      proteinuria, we could show that albuminuric rats and mice had abnormally elevated
      sodium-phosphate apical co-transporter expression, despite elevated fibroblast
      growth factor 23 (FGF23). The FGF23 downstream pathway was inhibited despite
      elevated FGF23 levels. Klotho protein expression was also lower in proteinuric
      animals compared to controls. Finally, albumin had no direct effects on phosphate
      transport in cells. Altogether, we show that albuminuria induces alteration of
      phosphate tubular handling, independently of glomerular filtration rate. The
      mechanisms involved appear to include Klotho down-regulation and resistance to
      FGF23. This observation may link albuminuria to increased cardiovascular disease
      via altered phosphate handling. Finally, this observation opens up further
      opportunities to better understand the link between albuminuria, Klotho, FGF23
      and phosphate handling.

PMID- 29063523
TI  - Evaluation of existing and desired antimicrobial stewardship activities and
      strategies in Swiss hospitals.
AB  - Antimicrobial stewardship (AMS) is an important component in the fight against
      antimicrobial resistance. Currently, few hospitals have an ongoing institutional
      AMS programme. Swissnoso - the national centre for infection prevention - has
      launched a national Swiss AMS initiative supported by the office of public
      health. To guide AMS priorities and resources, current AMS activities in
      Switzerland were assessed. We distributed an internet-based questionnaire
      directed mainly to board-certified infectious diseases specialists and, if not
      available, senior internal medicine staff. Responses were received from 63/134
      hospitals surveyed. More than 90% were in favour of national treatment guidelines
      currently in development under the umbrella of the Swiss society for infectious
      diseases. Many AMS activities - such as antimicrobial formulary restrictions and
      approval systems, review of antimicrobial prescriptions with point of care
      intervention, and direct feedback or therapeutic drug monitoring - are currently
      lacking in the majority of Swiss hospitals surveyed. Development of a modular
      formal AMS standard for Swiss hospitals may aid in advancing current AMS
      strategies and in introducing AMS programmes in Switzerland. In combination with
      the surveillance of antimicrobial use and resistance by ANRESIS, the national
      antimicrobial resistance surveillance system, this approach may reduce the use of
      antimicrobial agents and consequently the risk of emergence of multi-resistant
      pathogens.

PMID- 29063522
TI  - Remembering specific features of emotional events across time: The role of REM
      sleep and prefrontal theta oscillations.
AB  - When an episode of emotional significance is encountered, it often results in the
      formation of a highly resistant memory representation that is easily retrieved
      for many succeeding years. Recent research shows that beyond generic
      consolidation processes, rapid eye movement (REM) sleep importantly contributes
      to this effect. However, the boundary conditions of consolidation processes
      during REM sleep, specifically whether these extend to source memory, have not
      been examined extensively. The current study tested the effects of putative
      consolidation processes emerging during REM sleep and slow wave sleep (SWS) on
      item and source memory of negative and neutral images, respectively. Results
      demonstrate superior emotional relative to neutral item memory retention after
      both late night REM sleep and early night SWS. Emotional source memory, on the
      other hand, exhibited an attenuated decline following late night REM sleep,
      whereas neutral source memory was selectively preserved across early night SWS.
      This pattern of results suggests a selective preservation of emotional source
      memory during REM sleep that is functionally dissociable from SWS-dependent
      reprocessing of neutral source memory. This was further substantiated by a
      neurophysiological dissociation: Postsleep emotional source memory was
      selectively correlated with frontal theta lateralization (REM sleep), whereas
      postsleep neutral item memory was correlated with SWS spindle power. As such, the
      present results contribute to a more comprehensive characterization of sleep
      related consolidation mechanisms underlying emotional and neutral memory
      retention. Subsidiary analysis of emotional reactivity to previously encoded
      material revealed an enhancing rather than attenuating effect of late night REM
      sleep on emotional responses.

PMID- 29063525
TI  - Evaluation of the National Skin Cancer Campaign: a Swiss experience of
      Euromelanoma.
AB  - AIMS OF THE STUDY: Skin cancer is a burden to healthcare and patients worldwide.
      The incidence of skin cancer has been rising during recent decades and this trend
      is expected to continue in the future. Numerous risk factors have been identified
      and prevention strategies developed. The Euromelanoma campaign is a pan-European
      skin cancer prevention programme, targeted to both primary and secondary
      prevention of malignant melanoma. The current study aimed to evaluate the results
      of the Swiss skin cancer screening day 2016. METHODS: A questionnaire was used to
      obtain data on characteristics and suspected skin cancers of all participants.
      Follow-up of patients with suspicious lesions was performed 3 to 6 months later.
      RESULTS: During the campaign, 2795 people were screened. Of the screened
      individuals, 157 participants (58% female, 42% male; mean age 58.8 years)
      underwent further evaluations; 6 cutaneous malignant melanomas, 21 basal cell
      carcinomas and 2 squamous cell carcinomas were detected. Detection rates were
      0.21% for cutaneous melanoma, 0.75% for basal cell carcinoma and 0.07% for
      squamous cell carcinoma. CONCLUSIONS: Our study provides an up-to-date evaluation
      of the Swiss Euromelanoma campaign 2016. The results are mostly in line with data
      from other European studies. Considering the morbidity, mortality and financial
      and social impact of skin cancer, the capacity to raise awareness of risk
      factors, skin cancer prevention methods and educating high-risk and at-risk
      individuals, we may assume that a National Screening Day has a crucial impact on
      the public health system.

PMID- 29063526
TI  - Malaria cases in Switzerland from 2005 to 2015 and recent rise of imported
      Plasmodium vivax malaria.
AB  - Reporting cases of malaria to the Federal Office of Public Health has been
      mandatory in Switzerland since 1974. We analysed notifications of imported
      confirmed malaria cases between 2005 and 2015 in Switzerland or Liechtenstein.
      Data for previously visited countries, nationality and reason for travelling were
      analysed. In contrast with the impressive drop of malaria cases reported
      worldwide since 2000, we found that the number of malaria cases imported yearly
      in Switzerland doubled in 2014 and 2015 compared to the average for the preceding
      decade. Since 2014, Plasmodium vivax infection represented 36% of all diagnosed
      malaria cases in Switzerland, compared to 11% in the decade leading to 2013. Most
      of the vivax malaria patients originated from the Horn of Africa, especially from
      Eritrea. This rise in cases was a consequence not only of an increase in the
      number of Eritrean refugees, but also their vivax malaria incidence rate, which
      jumped from 1-30/00 previously to 120/00 in 2014. This is a trend that is not
      matched by national statistics in Eritrea. An unreported increased incidence in
      the country of origin (Eritrea) might be the cause of the rise of Pv cases
      imported into Switzerland, but infections are also likely to occur along the
      harsh and long migration journey. This epidemiology highlights the need to
      register and use primaquine for the treatment of latent-phase P. vivax malaria in
      Switzerland, a medicine currently neither marketed nor systematically reimbursed.
      Moreover, general practitioners should be aware of this specific epidemiological
      situation in order to avoid misdiagnosis of febrile Eritreans even months after
      they reach Switzerland.

PMID- 29063530
TI  - President's Statement.

PMID- 29063532
TI  - Transforming Data into Knowledge: How to Improve the Efficiency of Clinical Care?
AB  - Objectives: To provide an introduction to the 2017 IMIA Yearbook of Medical
      Informatics by the editors. Methods: We present a brief overview of the 2017
      special topic "Learning from experience: Secondary use of patient data". We
      review our choice of special topic section editors, present the new section
      "Health Information Management", and discuss transitions in the editorial team.
      Results: In this edition of the Yearbook, we focused on one of the most important
      issues for the medical informatics community: The secondary use of clinical data.
      With the ubiquitous adoption of electronic health records (EHRs) and the
      increasing availability of genomic and environmental data, as well as the
      accessibility of unstructured data in social media, issues related to data
      integration, storage, and management, as well as the need for novel analytic
      approaches are clear challenges. The paradigm of Learning Health Systems (LHSs)
      is presented in the keynote paper and survey papers review the significant
      developments in allied fields such as clinical research, clinical systems,
      translational informatics, and public health over the past two years. IMIA
      Working Groups also contributed to this topic. Conclusion: The 2017 issue of the
      IMIA yearbook focuses on the secondary use of patient data and presents the
      difficulties that still need to be solved before witnessing the actual
      development of LHSs.

PMID- 29063527
TI  - High participation rate among 25 721 patients with broad age range in a hospital
      based research project involving whole-genome sequencing - the Lausanne
      Institutional Biobank.
AB  - AIMS: We aimed to evaluate the interest of adult inpatients and selected
      outpatients in engaging in a large, real-life, hospital-based, genomic medicine
      research project and in receiving clinically actionable incidental findings.
      METHODS: Within the framework of the cross-sectional Institutional Biobank of
      Lausanne, Switzerland, a total of 25721 patients of the CHUV University Hospital
      were systematically invited to grant researchers access to their biomedical data
      and to donate blood for future analyses, including whole-genome sequencing.
      Multivariable logistic regression analysis was used to identify personal factors,
      including age, gender, religion, ethnicity, citizenship, education level and mode
      of admission, associated with willingness to participate in this genomic research
      project and with interest in receiving clinically actionable incidental findings.
      RESULTS: The overall participation rate was 79% (20343/25721). Participation rate
      declined progressively with age, averaging 83%, 75%, 67% and 62% in patients aged
      <64 years (n = 13108), >=64 years (n = 12613), >=80 years (n = 4557) and >=90
      years (n = 1050), respectively. Factors associated with participation
      substantially differed between age strata. Patients less likely to participate
      included women (odds ratio 0.86, [95% confidence interval 0.79-0.95] and 0.78
      [0.71-0.85] before and after age 64, respectively), non-Swiss (0.81 [0.74-0.90]
      and 0.58 [0.52-0.65]) and those admitted through the emergency ward (0.88 [0.79
      0.98] and 0.66 [0.60-0.73]). Religion and marital status were associated with
      participation among patients aged <64 years. A total of 19 018 (93%) participants
      were willing to be re-contacted for incidental findings. A high education level
      was associated with higher participation rate, but not with higher willingness to
      receive incidental findings within the population who had agreed to participate.
      CONCLUSION: A large proportion of adult patients, even among the elderly, are
      willing to actively participate and receive incidental findings in this
      systematic hospital-based precision and genomic medicine research program with
      broad consent.

PMID- 29063533
TI  - The International Academy of Health Sciences Informatics: An Academy of
      Excellence.

PMID- 29063535
TI  - Update on Data Reuse in Health Care.
AB  - Objective: Reuse of clinical data has broad use in clinical, research,
      governmental, and business settings. This summary provides an update on the
      benefits, barriers to use with large clinical databases, policy frameworks that
      have been formulated, and challenges. Methods: This report highlights some recent
      publications on the diverse uses of clinical data and some policy initiatives to
      promote reuse. It also contains the opinions of the author. Results: Although
      many examples of the benefits of data reuse have been documented, this summary
      also reviews why the quality of clinical data needs to be the focus of future
      informatics work. Conclusion: The promise of reusing data outweighs potential
      risks, but concerns about privacy and the need to modernize our legal framework
      will be necessary to realize the full benefits of real-world evidence.

PMID- 29063538
TI  - Health Information Management: Changing with Time.
AB  - Objective: With the evolution of patient medical records from paper to electronic
      media and the changes to the way data is sourced, used, and managed, there is an
      opportunity for health information management (HIM) to learn and facilitate the
      increasing expanse of available patient data. Methods: This paper discusses the
      emerging trends and lessons learnt in relation with the following four areas: 1)
      data and information governance, 2) terminology standards certification, 3)
      International Classification of Diseases, 11th edition (ICD-11), and 4) data
      analytics and HIM. Results: The governance of patient data and information
      increasingly requires the HIM profession to incorporate the roles of data
      scientists and data stewards into its portfolio to ensure data analytics and
      digital transformation is appropriately managed. Not only are terminology
      standards required to facilitate the structure and primary use of this data,
      developments in Canada in relation with the standards, role descriptions,
      framework and curricula in the form of certification provide one prime example of
      ensuring the quality of the secondary use of patient data. The impending
      introduction of ICD-11 brings with it the need for the HIM profession to manage
      the transition between ICD versions and country modifications incorporating
      changes to standards and tools, and the availability and type of patient data
      available for secondary use. Conclusions: In summary, the health information
      management profession now requires abilities in leadership, data, and informatics
      in addition to health information science and coding skills to facilitate the
      expanding secondary use of patient data.

PMID- 29063536
TI  - Secondary Use of Patient Data: Review of the Literature Published in 2016.
AB  - Objectives: To summarize recent research and emerging trends in the area of
      secondary use of healthcare data, and to present the best papers published in
      this field, selected to appear in the 2017 edition of the IMIA Yearbook. Methods:
      A literature review of articles published in 2016 and related to secondary use of
      healthcare data was performed using two bibliographic databases. From this
      search, 941 papers were identified. The section editors independently reviewed
      the papers for relevancy and impact, resulting in a consensus list of 14
      candidate best papers. External reviewers examined each of the candidate best
      papers and the final selection was made by the editorial board of the Yearbook.
      Results: From the 941 retrieved papers, the selection process resulted in four
      best papers. These papers discuss data quality concerns, issues in preserving
      privacy of patients in shared datasets, and methods of decision support when
      consuming large amounts of raw electronic health record (EHR) data. Conclusion:
      In 2016, a significant effort was put into the development of new systems which
      aim to avoid significant human understanding and pre-processing of healthcare
      data, though this is still only an emerging area of research. The value of
      temporal relationships between data received significant study, as did effective
      information sharing while preserving patient privacy.

PMID- 29063540
TI  - Findings from the 2017 Yearbook Section on Health Information Management.
AB  - Objectives: To summarize the recent literature and research and present a
      selection of the best papers published in 2016 in the field of Health Information
      Management (HIM). Methods: A systematic review of the literature for the IMIA
      Yearbook HIM section was performed by the two section editors with the help of a
      medical librarian. We searched bibliographic databases for HIM-related papers
      were searched using both MeSH headings and key words in titles and abstracts. A
      shortlist of candidate best papers was first selected by section editors before
      being peer-reviewed by independent external reviewers. Results: The five papers
      selected as 'Best Papers' illustrate a variety of themes, include authors from a
      variety of countries, and were published in some of the best journals in the
      field. The themes of the five best papers include health information exchange,
      personal health records, patient engagement, data quality, and e-quality
      measures. Conclusions: The discipline of Health Information Management is
      increasingly becoming allied with the field of Biomedical Informatics in that
      both disciplines have interests in common. Traditional HIM areas of expertise (in
      the pre-electronic health record world), such as coding and privacy and security
      of health information, are necessary for the electronic exchange and secondary
      use of health information. With the changes in healthcare delivery brought by the
      use of electronic health records, addressing issues of information governance is
      essential. This synopsis discusses these key issues at the intersection of HIM
      and informatics, examines the potential challenges, and points the way for best
      practices, future research, and public policy considerations and directions.

PMID- 29063543
TI  - Trends and Progress in Human Factors and Organizational Issues in 2016: Learning
      from Experience.
AB  - Objective: To summarize significant research contributions on human factors and
      organizational issues in medical informatics published in 2016. Methods: An
      extensive search using PubMed/Medline and Web of Science(r) was conducted to
      identify the scientific contributions published in 2016 that address human
      factors and organizational issues in medical informatics. The selection process
      comprised three steps: (i) 15 candidate best papers were first selected by the
      two section editors, (ii) external reviewers from internationally renowned
      research teams reviewed each candidate best paper, and (iii) the final selection
      of five best papers was conducted by the editorial board of the Yearbook.
      Results: The five selected best papers present studies with rigorous methods,
      properly designed and described and are, therefore, efficiently reusable for
      other researches. Conclusion: Human factors and ergonomics- based interventions
      must be tailored to the context, but meaningful ways must be simultaneously found
      to generate a stronger evidence base for research and to provide efficient, easy
      to implement, and useful methods.

PMID- 29063542
TI  - Are We There Yet? Human Factors Knowledge and Health Information Technology - the
      Challenges of Implementation and Impact.
AB  - Objective: To review the developments in human factors (HF) research on the
      challenges of health information technology (HIT) implementation and impact given
      the continuing incidence of usability problems and unintended consequences from
      HIT development and use. Methods: A search of PubMed/Medline and Web of
      Science(r) identified HF research published in 2015 and 2016. Electronic health
      records (EHRs) and patient-centred HIT emerged as significant foci of recent HF
      research. The authors selected prominent papers highlighting ongoing HF and
      usability challenges in these areas. This selective rather than systematic review
      of recent HF research highlights these key challenges and reflects on their
      implications on the future impact of HF research on HIT. Results: Research
      provides evidence of continued poor design, implementation, and usability of HIT,
      as well as technology-induced errors and unintended consequences. The paper
      highlights support for: (i) strengthening the evidence base on the benefits of HF
      approaches; (ii) improving knowledge translation in the implementation of HF
      approaches during HIT design, implementation, and evaluation; (iii) increasing
      transparency, governance, and enforcement of HF best practices at all stages of
      the HIT system development life cycle. Discussion and Conclusion: HF and
      usability approaches are yet to become embedded as integral components of HIT
      development, implementation, and impact assessment. As HIT becomes ever-more
      pervasive including with patients as end-users, there is a need to expand our
      conceptualisation of the problems to be addressed and the suite of tactics and
      strategies to be used to calibrate our pro-active involvement in its improvement.

PMID- 29063547
TI  - Clinical Information Systems as the Backbone of a Complex Information Logistics
      Process: Findings from the Clinical Information Systems Perspective for 2016.
AB  - Objective: To summarize recent research and to propose a selection of best papers
      published in 2016 in the field of Clinical Information Systems (CIS). Method: The
      query used to retrieve the articles for the CIS section of the 2016 edition of
      the IMIA Yearbook of Medical Informatics was reused. It again aimed at
      identifying relevant publications in the field of CIS from PubMed and Web of
      Science and comprised search terms from the Medical Subject Headings (MeSH)
      catalog as well as additional free text search terms. The retrieved articles were
      categorized in a multi-pass review carried out by the two section editors. The
      final selection of candidate papers was then peer-reviewed by Yearbook editors
      and external reviewers. Based on the review results, the best papers were then
      chosen at the selection meeting with the IMIA Yearbook editorial board. Text
      mining, term co-occurrence mapping, and topic modelling techniques were used to
      get an overview on the content of the retrieved articles. Results: The query was
      carried out in mid-January 2017, yielding a consolidated result set of 2,190
      articles published in 921 different journals. Out of them, 14 papers were
      nominated as candidate best papers and three of them were finally selected as the
      best papers of the CIS field. The content analysis of the articles revealed the
      broad spectrum of topics covered by CIS research. Conclusions: The CIS field is
      multi-dimensional and complex. It is hard to draw a well-defined outline between
      CIS and other domains or other sections of the IMIA Yearbook. The trends observed
      in the previous years are progressing. Clinical information systems are more than
      just sociotechnical systems for data collection, processing, exchange,
      presentation, and archiving. They are the backbone of a complex, trans
      institutional information logistics process.

PMID- 29063545
TI  - Grappling with the Future Use of Big Data for Translational Medicine and Clinical
      Care.
AB  - Objectives: Although patients may have a wealth of imaging, genomic, monitoring,
      and personal device data, it has yet to be fully integrated into clinical care.
      Methods: We identify three reasons for the lack of integration. The first is that
      "Big Data" is poorly managed by most Electronic Medical Record Systems (EMRS).
      The data is mostly available on "cloud-native" platforms that are outside the
      scope of most EMRs, and even checking if such data is available on a patient
      often must be done outside the EMRS. The second reason is that extracting
      features from the Big Data that are relevant to healthcare often requires complex
      machine learning algorithms, such as determining if a genomic variant is protein
      altering. The third reason is that applications that present Big Data need to be
      modified constantly to reflect the current state of knowledge, such as
      instructing when to order a new set of genomic tests. In some cases, applications
      need to be updated nightly. Results: A new architecture for EMRS is evolving
      which could unite Big Data, machine learning, and clinical care through a
      microservice-based architecture which can host applications focused on quite
      specific aspects of clinical care, such as managing cancer immunotherapy.
      Conclusion: Informatics innovation, medical research, and clinical care go hand
      in hand as we look to infuse science-based practice into healthcare. Innovative
      methods will lead to a new ecosystem of applications (Apps) interacting with
      healthcare providers to fulfill a promise that is still to be determined.

PMID- 29063550
TI  - Sensor, Signal, and Imaging Informatics.
AB  - Objective: To summarize significant contributions to sensor, signal, and imaging
      informatics published in 2016. Methods: We conducted an extensive search using
      PubMed(r) and Web of Science(r) to identify the scientific contributions
      published in 2016 that addressed sensors, signals, and imaging in medical
      informatics. The three section editors selected 15 candidate best papers by
      consensus. Each candidate article was reviewed by the section editors and at
      least two other external reviewers. The final selection of the six best papers
      was conducted by the editorial board of the Yearbook. Results: The selected
      papers of 2016 demonstrate the important scientific advances in management and
      analysis of sensor, signal, and imaging information. Conclusion: The growing
      volume of signal and imaging data provides exciting new challenges and
      opportunities for research in medical informatics. Evolving technologies provide
      faster and more effective approaches for pattern recognition and diagnostic
      evaluation. The papers selected here offer a small glimpse of the high-quality
      scientific work published in 2016 in the domain of sensor, signal, and imaging
      informatics.

PMID- 29063549
TI  - An Assessment of Imaging Informatics for Precision Medicine in Cancer.
AB  - Objectives: Precision medicine requires the measurement, quantification, and
      cataloging of medical characteristics to identify the most effective medical
      intervention. However, the amount of available data exceeds our current capacity
      to extract meaningful information. We examine the informatics needs to achieve
      precision medicine from the perspective of quantitative imaging and oncology.
      Methods: The National Cancer Institute (NCI) organized several workshops on the
      topic of medical imaging and precision medicine. The observations and
      recommendations are summarized herein. Results: Recommendations include: use of
      standards in data collection and clinical correlates to promote interoperability;
      data sharing and validation of imaging tools; clinician's feedback in all phases
      of research and development; use of open-source architecture to encourage
      reproducibility and reusability; use of challenges which simulate real-world
      situations to incentivize innovation; partnership with industry to facilitate
      commercialization; and education in academic communities regarding the challenges
      involved with translation of technology from the research domain to clinical
      utility and the benefits of doing so. Conclusions: This article provides a survey
      of the role and priorities for imaging informatics to help advance quantitative
      imaging in the era of precision medicine. While these recommendations were drawn
      from oncology, they are relevant and applicable to other clinical domains where
      imaging aids precision medicine.

PMID- 29063552
TI  - Advances in Clinical Decision Support: Highlights of Practice and the Literature
      2015-2016.
AB  - Introduction: Advances in clinical decision support (CDS) continue to evolve to
      support the goals of clinicians, policymakers, patients and professional
      organizations to improve clinical practice, patient safety, and the quality of
      care. Objectives: Identify key thematic areas or foci in research and practice
      involving clinical decision support during the 2015-2016 time period. Methods:
      Thematic analysis consistent with a grounded theory approach was applied in a
      targeted review of journal publications, the proceedings of key scientific
      conferences as well as activities in standards development organizations in order
      to identify the key themes underlying work related to CDS. Results: Ten key
      thematic areas were identified, including: 1) an emphasis on knowledge
      representation, with a focus on clinical practice guidelines; 2) various aspects
      of precision medicine, including the use of sensor and genomic data as well as
      big data; 3) efforts in quality improvement; 4) innovative uses of computer-based
      provider order entry (CPOE) systems, including relevant data displays; 5)
      expansion of CDS in various clinical settings; 6) patient-directed CDS; 7)
      understanding the potential negative impact of CDS; 8) obtaining structured data
      to drive CDS interventions; 9) the use of diagnostic decision support; and 10)
      the development and use of standards for CDS. Conclusions: Active research and
      practice in 2015-2016 continue to underscore the importance and broad utility of
      CDS for effecting change and improving the quality and outcome of clinical care.

PMID- 29063553
TI  - Contributions from the 2016 Literature on Clinical Decision Support.
AB  - Objectives: To summarize recent research and select the best papers published in
      2016 in the field of computerized clinical decision support for the Decision
      Support section of the IMIA yearbook. Methods: A literature review was performed
      by searching two bibliographic databases for papers related to clinical decision
      support systems (CDSSs). The aim was to identify a list of candidate best papers
      from the retrieved papers that were then peer-reviewed by external reviewers. A
      consensus meeting of the IMIA editorial team finally selected the best papers on
      the basis of all reviews and section editor evaluation. Results: Among the 1,145
      retrieved papers, the entire review process resulted in the selection of four
      best papers. The first paper describes machine learning models used to predict
      breast cancer multidisciplinary team decisions and compares them with two
      predictors based on guideline knowledge. The second paper introduces a linked
      data approach for publication, discovery, and interoperability of CDSSs. The
      third paper assessed the variation in high-priority drug-drug interaction (DDI)
      alerts across 14 Electronic Health Record systems, operating in different
      institutions in the US. The fourth paper proposes a generic framework for
      modeling multiple concurrent guidelines and detecting their recommendation
      interactions using semantic web technologies. Conclusions: The process of
      identifying and selecting best papers in the domain of CDSSs demonstrated that
      the research in this field is very active concerning diverse dimensions, such as
      the types of CDSSs, e.g. guideline-based, machine-learning-based, knowledge
      fusion-based, etc., and addresses challenging areas, such as the concurrent
      application of multiple guidelines for comorbid patients, the resolution of
      interoperability issues, and the evaluation of CDSSs. Nevertheless, this process
      also showed that CDSSs are not yet fully part of the digitalized healthcare
      ecosystem. Many challenges remain to be faced with regard to the evidence of
      their output, the dissemination of their technologies, as well as their adoption
      for better and safer healthcare delivery.

PMID- 29063556
TI  - Knowledge Representation and Management, It's Time to Integrate!
AB  - Objectives: To select, present, and summarize the best papers published in 2016
      in the field of Knowledge Representation and Management (KRM). Methods: A
      comprehensive and standardized review of the medical informatics literature was
      performed based on a PubMed query. Results: Among the 1,421 retrieved papers, the
      review process resulted in the selection of four best papers focused on the
      integration of heterogeneous data via the development and the alignment of
      terminological resources. In the first article, the authors provide a curated and
      standardized version of the publicly available US FDA Adverse Event Reporting
      System. Such a resource will improve the quality of the underlying data, and
      enable standardized analyses using common vocabularies. The second article
      describes a project developed in order to facilitate heterogeneous data
      integration in the i2b2 framework. The originality is to allow users integrate
      the data described in different terminologies and to build a new repository, with
      a unique model able to support the representation of the various data. The third
      paper is dedicated to model the association between multiple phenotypic traits
      described within the Human Phenotype Ontology (HPO) and the corresponding
      genotype in the specific context of rare diseases (rare variants). Finally, the
      fourth paper presents solutions to annotation-ontology mapping in genome-scale
      data. Of particular interest in this work is the Experimental Factor Ontology
      (EFO) and its generic association model, the Ontology of Biomedical AssociatioN
      (OBAN). Conclusion: Ontologies have started to show their efficiency to integrate
      medical data for various tasks in medical informatics: electronic health records
      data management, clinical research, and knowledge-based systems development.

PMID- 29063555
TI  - Representing Knowledge Consistently Across Health Systems.
AB  - Objectives: Electronic health records (EHRs) have increasingly emerged as a
      powerful source of clinical data that can be leveraged for reuse in research and
      in modular health apps that integrate into diverse health information
      technologies. A key challenge to these use cases is representing the knowledge
      contained within data from different EHR systems in a uniform fashion. Method: We
      reviewed several recent studies covering the knowledge representation in the
      common data models for the Observational Medical Outcomes Partnership (OMOP) and
      its Observational Health Data Sciences and Informatics program, and the United
      States Patient Centered Outcomes Research Network (PCORNet). We also reviewed the
      Health Level 7 Fast Healthcare Interoperability Resource standard supporting app
      like programs that can be used across multiple EHR and research systems. Results:
      There has been a recent growth in high-impact efforts to support quality-assured
      and standardized clinical data sharing across different institutions and EHR
      systems. We focused on three major efforts as part of a larger landscape moving
      towards shareable, transportable, and computable clinical data. Conclusion: The
      growth in approaches to developing common data models to support interoperable
      knowledge representation portends an increasing availability of high-quality
      clinical data in support of research. Building on these efforts will allow a
      future whereby significant portions of the populations in the world may be able
      to share their data for research.

PMID- 29063559
TI  - Present and Future Trends in Consumer Health Informatics and Patient-Generated
      Health Data.
AB  - Objectives: Consumer Health Informatics (CHI) and the use of Patient-Generated
      Health Data (PGHD) are rapidly growing focus areas in healthcare. The objective
      of this paper is to briefly review the literature that has been published over
      the past few years and to provide a sense of where the field is going. Methods:
      We searched PubMed and the ACM Digital Library for articles published between
      2014 and 2016 on the topics of CHI and PGHD. The results of the search were
      screened for relevance and categorized into a set of common themes. We discuss
      the major topics covered in these articles. Results: We retrieved 65 articles
      from our PubMed query and 32 articles from our ACM Digital Library query. After a
      review of titles, we were left with 47 articles to conduct our full article
      survey of the activities in CHI and PGHD. We have summarized these articles and
      placed them into major categories of activity. Within the domain of consumer
      health informatics, articles focused on mobile health and patient-generated
      health data comprise the majority of the articles published in recent years.
      Conclusions: Current evidence indicates that technological advancements and the
      widespread availability of affordable consumer-grade devices are fueling research
      into using PGHD for better care. As we observe a growing number of (pilot)
      developments using various mobile health technologies to collect PGHD, major gaps
      still exist in how to use the data by both patients and providers. Further
      research is needed to understand the impact of PGHD on clinical outcomes.

PMID- 29063560
TI  - Secondary Use of Recorded or Self-expressed Personal Data: Consumer Health
      Informatics and Education in the Era of Social Media and Health Apps.
AB  - Objective: To summarize the state of the art during the year 2016 in the areas
      related to consumer health informatics and education with a special emphasis in
      secondary use of patient data. Methods: We conducted a systematic review of
      articles published in 2016, using PubMed with a predefined set of queries. We
      identified over 320 potential articles for review. Papers were considered
      according to their relevance for the topic of the section. Using consensus, we
      selected the 15 most representative papers, which were submitted to external
      reviewers for full review and scoring. Based on the scoring and quality criteria,
      five papers were finally selected as best papers Results: The five best papers
      can be grouped in two major areas: 1) methods and tools to identify and collect
      formal requirements for secondary use of data, and 2) innovative topics
      highlighting the interest of carrying on "secondary" studies on patient data,
      more specifically on the data self-expressed by patients through social media
      tools. Regarding the formal requirements about informed consent, the selected
      papers report a comparison of legal aspects in European countries to find a
      common and unified grammar around the concept of "data donation". Regarding
      innovative approaches to value patient data, the selected papers report machine
      learning algorithms to extract knowledge from patient experience and satisfaction
      with health care delivery, drug and medication use, treatment compliance and
      barriers during cancer disease, or acceptation of public health actions such as
      vaccination. Conclusions: Secondary use of patient data (apart from personal
      health care record data) can be expressed according to many ways. Requirements to
      allow this secondary use have to be harmonized between countries, and social
      media platforms can be efficiently used to explore and create knowledge on
      patient experience with health problems or activities. Machine learning
      algorithms can explore those massive amounts of data to support health care
      professionals, and institutions provide more accurate knowledge about use and
      usage, behaviour, sentiment, or satisfaction about health care delivery.

PMID- 29063562
TI  - A Review of Recent Advances in Translational Bioinformatics: Bridges from Biology
      to Medicine.
AB  - Objectives: To highlight and provide insights into key developments in
      translational bioinformatics between 2014 and 2016. Methods: This review
      describes some of the most influential bioinformatics papers and resources that
      have been published between 2014 and 2016 as well as the national genome
      sequencing initiatives that utilize these resources to routinely embed genomic
      medicine into healthcare. Also discussed are some applications of the secondary
      use of patient data followed by a comprehensive view of the open challenges and
      emergent technologies. Results: Although data generation can be performed
      routinely, analyses and data integration methods still require active research
      and standardization to improve streamlining of clinical interpretation. The
      secondary use of patient data has resulted in the development of novel algorithms
      and has enabled a refined understanding of cellular and phenotypic mechanisms.
      New data storage and data sharing approaches are required to enable diverse
      biomedical communities to contribute to genomic discovery. Conclusion: The
      translation of genomics data into actionable knowledge for use in healthcare is
      transforming the clinical landscape in an unprecedented way. Exciting and
      innovative models that bridge the gap between clinical and academic research are
      set to open up the field of translational bioinformatics for rapid growth in a
      digital era.

PMID- 29063566
TI  - Clinical Research Informatics: Contributions from 2016.
AB  - Objectives: To summarize key contributions to current research in the field of
      Clinical Research Informatics (CRI) and to select the best papers published in
      2016. Methods: A bibliographic search using a combination of MeSH and free terms
      on CRI was performed using PubMed, followed by a double-blind review in order to
      select a list of candidate best papers to be then peer-reviewed by external
      reviewers. A consensus meeting between the two section editors and the editorial
      team was organized to finally conclude on the selection of best papers. Results:
      Among the 452 papers published in 2016 in the various areas of CRI and returned
      by the query, the full review process selected four best papers. The authors of
      the first paper utilized a comprehensive representation of the patient medical
      record and semi-automatically labeled training sets to create phenotype models
      via a machine learning process. The second selected paper describes an open
      source tool chain securely connecting ResearchKit compatible applications (Apps)
      to the widely-used clinical research infrastructure Informatics for Integrating
      Biology and the Bedside (i2b2). The third selected paper describes the FAIR
      Guiding Principles for scientific data management and stewardship. The fourth
      selected paper focuses on the evaluation of the risk of privacy breaches in
      releasing genomics datasets. Conclusions: A major trend in the 2016 publications
      is the variety of research on "real-world data" - healthcare-generated data,
      person health data, and patient-reported outcomes -highlighting the opportunities
      provided by new machine learning techniques as well as new potential risks of
      privacy breaches.

PMID- 29063565
TI  - Clinical Research Informatics: Supporting the Research Study Lifecycle.
AB  - Objectives: The primary goal of this review is to summarize significant
      developments in the field of Clinical Research Informatics (CRI) over the years
      2015-2016. The secondary goal is to contribute to a deeper understanding of CRI
      as a field, through the development of a strategy for searching and classifying
      CRI publications. Methods: A search strategy was developed to query the PubMed
      database, using medical subject headings to both select and exclude articles, and
      filtering publications by date and other characteristics. A manual review
      classified publications using stages in the "research study lifecycle", with key
      stages that include study definition, participant enrollment, data management,
      data analysis, and results dissemination. Results: The search strategy generated
      510 publications. The manual classification identified 125 publications as
      relevant to CRI, which were classified into seven different stages of the
      research lifecycle, and one additional class that pertained to multiple stages,
      referring to general infrastructure or standards. Important cross-cutting themes
      included new applications of electronic media (Internet, social media, mobile
      devices), standardization of data and procedures, and increased automation
      through the use of data mining and big data methods. Conclusions: The review
      revealed increased interest and support for CRI in large-scale projects across
      institutions, regionally, nationally, and internationally. A search strategy
      based on medical subject headings can find many relevant papers, but a large
      number of non-relevant papers need to be detected using text words which pertain
      to closely related fields such as computational statistics and clinical
      informatics. The research lifecycle was useful as a classification scheme by
      highlighting the relevance to the users of clinical research informatics
      solutions.

PMID- 29063568
TI  - Capturing the Patient's Perspective: a Review of Advances in Natural Language
      Processing of Health-Related Text.
AB  - Background: Natural Language Processing (NLP) methods are increasingly being
      utilized to mine knowledge from unstructured health-related texts. Recent
      advances in noisy text processing techniques are enabling researchers and medical
      domain experts to go beyond the information encapsulated in published texts
      (e.g., clinical trials and systematic reviews) and structured questionnaires, and
      obtain perspectives from other unstructured sources such as Electronic Health
      Records (EHRs) and social media posts. Objectives: To review the recently
      published literature discussing the application of NLP techniques for mining
      health-related information from EHRs and social media posts. Methods: Literature
      review included the research published over the last five years based on searches
      of PubMed, conference proceedings, and the ACM Digital Library, as well as on
      relevant publications referenced in papers. We particularly focused on the
      techniques employed on EHRs and social media data. Results: A set of 62 studies
      involving EHRs and 87 studies involving social media matched our criteria and
      were included in this paper. We present the purposes of these studies, outline
      the key NLP contributions, and discuss the general trends observed in the field,
      the current state of research, and important outstanding problems. Conclusions:
      Over the recent years, there has been a continuing transition from lexical and
      rule-based systems to learning-based approaches, because of the growth of
      annotated data sets and advances in data science. For EHRs, publicly available
      annotated data is still scarce and this acts as an obstacle to research progress.
      On the contrary, research on social media mining has seen a rapid growth,
      particularly because the large amount of unlabeled data available via this
      resource compensates for the uncertainty inherent to the data. Effective
      mechanisms to filter out noise and for mapping social media expressions to
      standard medical concepts are crucial and latent research problems. Shared tasks
      and other competitive challenges have been driving factors behind the
      implementation of open systems, and they are likely to play an imperative role in
      the development of future systems.

PMID- 29063569
TI  - Making Sense of Big Textual Data for Health Care: Findings from the Section on
      Clinical Natural Language Processing.
AB  - Objectives: To summarize recent research and present a selection of the best
      papers published in 2016 in the field of clinical Natural Language Processing
      (NLP). Method: A survey of the literature was performed by the two section
      editors of the IMIA Yearbook NLP section. Bibliographic databases were searched
      for papers with a focus on NLP efforts applied to clinical texts or aimed at a
      clinical outcome. Papers were automatically ranked and then manually reviewed
      based on titles and abstracts. A shortlist of candidate best papers was first
      selected by the section editors before being peer-reviewed by independent
      external reviewers. Results: The five clinical NLP best papers provide a
      contribution that ranges from emerging original foundational methods to
      transitioning solid established research results to a practical clinical setting.
      They offer a framework for abbreviation disambiguation and coreference
      resolution, a classification method to identify clinically useful sentences, an
      analysis of counseling conversations to improve support to patients with mental
      disorder and grounding of gradable adjectives. Conclusions: Clinical NLP
      continued to thrive in 2016, with an increasing number of contributions towards
      applications compared to fundamental methods. Fundamental work addresses
      increasingly complex problems such as lexical semantics, coreference resolution,
      and discourse analysis. Research results translate into freely available tools,
      mainly for English.

PMID- 29063571
TI  - Health Data for Public Health: Towards New Ways of Combining Data Sources to
      Support Research Efforts in Europe.
AB  - Objectives: To present the European landscape regarding the re-use of health
      administrative data for research. Methods: We present some collaborative projects
      and solutions that have been developed by Nordic countries, Italy, Spain, France,
      Germany, and the UK, to facilitate access to their health data for research
      purposes. Results: Research in public health is transitioning from siloed systems
      to more accessible and re-usable data resources. Following the example of the
      Nordic countries, several European countries aim at facilitating the re-use of
      their health administrative databases for research purposes. However, the
      ecosystem is still a complex patchwork, with different rules, policies, and
      processes for data provision. Conclusion: The challenges are such that with the
      abundance of health administrative data, only a European, overarching public
      health research infrastructure, is able to efficiently facilitate access to this
      data and accelerate research based on these highly valuable resources.

PMID- 29063574
TI  - Public Health and Epidemiology Informatics.
AB  - Objectives: To summarize current research in the field of Public Health and
      Epidemiology Informatics. Methods: The complete 2016 literature concerning public
      health and epidemiology informatics has been searched in PubMed and Web of
      Science, and the returned references were reviewed by the two section editors to
      select 14 candidate best papers. These papers were then peer-reviewed by external
      reviewers to allow the editorial team an enlightened selection of the best
      papers. Results: Among the 829 references retrieved from PubMed and Web of
      Science, three were finally selected as best papers. The first one compares
      Google, Twitter, and Wikipedia as tools for Influenza surveillance. The second
      paper presents a Geographic Knowledge-Based Model for mapping suitable areas for
      Rift Valley fever transmission in Eastern Africa. The last paper evaluates the
      factors associated with the visit of Facebook pages devoted to Public Health
      Communication. Conclusions: Surveillance is still a productive topic in public
      health informatics but other very important topics in public health are
      appearing.

PMID- 29063572
TI  - Public Health, Population Health, and Epidemiology Informatics: Recent Research
      and Trends in the United States.
AB  - Objectives: To survey advances in public and population health and epidemiology
      informatics over the past 18 months. Methods: We conducted a review of English
      language research works conducted in the domain of public and population health
      informatics and published in MEDLINE or Web of Science between January 2015 and
      June 2016 where information technology or informatics was a primary subject or
      main component of the study methodology. Selected articles were presented using a
      thematic analysis based on the 2011 American Medical Informatics Association
      (AMIA) Public Health Informatics Agenda tracks as a typology. Results: Results
      are given within the context developed by Dixon et al., (2015) and key themes
      from the 2011 AMIA Public Health Informatics Agenda. Advances are presented
      within a socio-technical infrastructure undergirded by a trained, competent
      public health workforce, systems development to meet the business needs of the
      practice field, and research that evaluates whether those needs are adequately
      met. The ability to support and grow the infrastructure depends on financial
      sustainability. Conclusions: The fields of public health and population health
      informatics continue to grow, with the most notable developments focused on
      surveillance, workforce development, and linking to or providing clinical
      services, which encompassed population health informatics advances. Very few
      advances addressed the need to improve communication, coordination, and
      consistency with the field of informatics itself, as identified in the AMIA
      agenda. This will likely result in the persistence of the silos of public health
      information systems that currently exist. Future research activities need to aim
      toward a holistic approach of informatics across the enterprise.

PMID- 29063583
TI  - Infrared Red Intubation System (IRRIS) guided flexile videoscope assisted
      difficult airway management.
AB  - BACKGROUND: Tracheal intubation with a flexible scope is a cornerstone technique
      in patients with severely difficult airways, but may fail. We report on a
      technique, Infrared Red Intubation System (IRRIS), that seems to facilitate the
      identification of the glottis. METHODS: The IRRIS is placed over the patient's
      cricothyroid membrane and emits blinking infrared light through the patient's
      skin into the subglottic space. When a flexible videoscope (one that does not
      filter infrared light) is introduced into the airway, it will display this as a
      blinking white light emerging from the glottis, retrograde transillumination,
      showing the pathway to the trachea. We have introduced this as an adjunct when
      managing our patients with difficult airways. We describe the technique and
      retrospectively report on the first ten patients where it was used. RESULTS: All
      ten patients had significant pathology in the airway, radiation therapy,
      predictors for difficult intubation and/or morbid obesity. In all cases the
      blinking light was visible during the flexible endoscopy and provided unambiguous
      identification of the glottis, from a distance. The blinking nature of the light
      from the IRRIS helped to distinguish it from the reflections in the mucosa that
      inevitably arise when the mucosa is hit by the light from the flexible scope
      itself. CONCLUSION: The addition of the IRRIS technique to intubation with
      flexible videoscopes may be a tool that will make intubation of the most
      difficult airways easier and may be of special help to the clinician who only
      rarely uses flexible videoscopes for tracheal intubation.

PMID- 29063584
TI  - Structural brain abnormalities in genetic generalized epilepsies: A systematic
      review and meta-analysis.
AB  - According to the International League Against Epilepsy (ILAE) definition, no
      structural abnormalities are present on a standard brain magnetic resonance image
      in genetic generalized epilepsy (GGE) patients. However, recent studies raise
      contradictory evidence with increasing use of quantitative magnetic resonance
      imaging techniques. Following PRISMA guidelines, a systematic, quantitative
      review was conducted using 28 peer-reviewed, case-control studies published after
      1989. Furthermore, a meta-analysis with a random-effect model revealed
      differences in structural brain abnormalities between GGE patients and controls.
      Significant structural differences between GGE and healthy controls were observed
      with volume reductions in whole brain, thalamus, putamen, caudate, pallidum, and
      supplementary motor area. Furthermore, gray matter volume reduction in the right
      and left hemispheres, thalamus, and insula, and surface area reduction in the
      caudal anterior cingulate cortex were revealed, along with gray matter increase
      in the medial frontal gyrus. Due to methodological differences, findings should
      be interpreted with caution. Nevertheless, contrary to the ILAE definition, it
      would appear that structural brain abnormalities may be present in GGE patients.
      Findings are consistent with a hypothesis regarding the underlying involvement of
      the thalamocortical networks in the generation of generalized spike-wave
      discharges, but structural abnormalities appear to extend outside these regions
      to potentially involve attention and other cognitive domains.

PMID- 29063585
TI  - Early (< 8 days) systemic postnatal corticosteroids for prevention of
      bronchopulmonary dysplasia in preterm infants.
AB  - BACKGROUND: Bronchopulmonary dysplasia remains a major problem in neonatal
      intensive care units. Persistent inflammation in the lungs is the most likely
      underlying pathogenesis. Corticosteroids have been used to prevent or treat
      bronchopulmonary dysplasia because of their potent anti-inflammatory effects.
      OBJECTIVES: To examine the relative benefits and adverse effects of systemic
      postnatal corticosteroids commenced within the first seven days of life for
      preterm infants at risk of developing bronchopulmonary dysplasia. SEARCH METHODS:
      For the 2017 update, we used the standard search strategy of Cochrane Neonatal to
      search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue
      1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013
      to 21 February 2017); and the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL) (January 2013 to 21 February 2017). We also searched clinical
      trials databases, conference proceedings, and reference lists of retrieved
      articles for randomised controlled trials (RCTs) and quasi-randomised trials.
      SELECTION CRITERIA: For this review, we selected RCTs examining systemic
      postnatal corticosteroid treatment within the first seven days of life (early) in
      high-risk preterm infants. Most studies evaluated the use of dexamethasone, but
      we also included studies that assessed hydrocortisone, even when used primarily
      for management of hypotension. DATA COLLECTION AND ANALYSIS: We used the GRADE
      approach to assess the quality of evidence.We extracted and analysed data
      regarding clinical outcomes that included mortality, bronchopulmonary dysplasia,
      death or bronchopulmonary dysplasia, failure to extubate, complications during
      primary hospitalisation, and long-term health outcomes. MAIN RESULTS: We included
      32 RCTs enrolling a total of 4395 participants. The overall risk of bias of
      included studies was probably low, as all were RCTs, and most trials used
      rigorous methods. Investigators reported significant benefits for the following
      outcomes overall: lower rates of failure to extubate, decreased risks of
      bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual
      age, death or bronchopulmonary dysplasia at 28 days of life and at 36 weeks'
      postmenstrual age, patent ductus arteriosus, and retinopathy of prematurity
      (ROP), including severe ROP. Researchers found no significant differences in
      rates of neonatal or subsequent mortality; they noted that gastrointestinal
      bleeding and intestinal perforation were important adverse effects, and that
      risks of hyperglycaemia, hypertension, hypertrophic cardiomyopathy, and growth
      failure were increased. The 13 trials that reported late outcomes described
      several adverse neurological effects at follow-up examination, including cerebral
      palsy. However, study authors indicated that major neurosensory disability was
      not significantly increased, either overall in the eight studies for which this
      outcome could be determined, or in the two individual studies in which rates of
      cerebral palsy or abnormal neurological examination were significantly increased.
      Moreover, data show that rates of the combined outcomes of death or cerebral
      palsy, or of death or major neurosensory disability, were not significantly
      increased. Two-thirds of studies used dexamethasone (n = 21). Subgroup analyses
      by type of corticosteroid revealed that most of the beneficial and harmful
      effects of treatment were attributable to dexamethasone. However, as with
      dexamethasone, hydrocortisone was associated with reduced rates of patent ductus
      arteriosus, mortality, and the combined outcome of mortality or chronic lung
      disease, but with increased occurrence of intestinal perforation. Results showed
      that hydrocortisone was not associated with obvious longer-term problems.Use of
      the GRADE approach revealed that the quality of evidence was high for the major
      outcomes considered, but review authors downgraded quality one level for several
      outcomes (mortality at latest age, bronchopulmonary dysplasia at 36 weeks, and
      death or bronchopulmonary dysplasia at 36 weeks) because of weak evidence of
      publication bias or moderate heterogeneity (death or cerebral palsy). AUTHORS'
      CONCLUSIONS: Benefits of early postnatal corticosteroid treatment (<= 7 days),
      particularly dexamethasone, may not outweigh adverse effects associated with this
      treatment. Although early corticosteroid treatment facilitates extubation and
      reduces risk of bronchopulmonary dysplasia and patent ductus arteriosus, it
      causes short-term adverse effects including gastrointestinal bleeding, intestinal
      perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy, and
      growth failure. Long-term follow-up studies report increased risk of abnormal
      findings on neurological examination and increased risk of cerebral palsy.
      However, the methodological quality of studies examining long-term outcomes is
      limited in some cases: Surviving children have been assessed predominantly before
      school age; no study has been sufficiently powered to detect important adverse
      long-term neurosensory outcomes; and no study has been designed with survival
      free of adverse long-term neurodevelopmental disability as the primary outcome.
      There is a compelling need for long-term follow-up and reporting of late
      outcomes, especially neurological and developmental outcomes, among surviving
      infants who participated in all randomised trials of early postnatal
      corticosteroid treatment. Hydrocortisone reduced rates of patent ductus
      arteriosus, of mortality, and of the combined outcome of mortality or
      bronchopulmonary dysplasia, without causing any obvious long-term harm. However,
      gastrointestinal perforation was more frequent in the hydrocortisone group.
      Longer-term follow-up into late childhood is vital for assessment of important
      effects or other effects that cannot be assessed in early childhood, such as
      effects of early hydrocortisone treatment on higher-order neurological functions,
      including cognitive function, academic performance, behaviour, mental health, and
      motor function. Further randomised controlled trials of early hydrocortisone
      should include longer-term survival free of neurodevelopmental disability as the
      main outcome.

PMID- 29063586
TI  - Protein expression during early stages of bone regeneration under hydrophobic and
      hydrophilic titanium domes. A pilot study.
AB  - BACKGROUND AND OBJECTIVES: There is significant evidence that, during the early
      stages of osseointegration, moderately rough hydrophilic (SLActive) surfaces can
      accelerate osteogenesis and increase bone-to-implant contact in comparison to
      hydrophobic (SLA) surfaces. However, very little is known regarding the molecular
      mechanisms behind the influence that surface chemistry modifications to increase
      hydrophilicity determine on bone healing. The aim of this study was to describe
      for the first time the proteins and related signalling pathways expressed during
      early osseous healing stages under SLA and SLActive titanium domes for guided
      bone regeneration. MATERIAL AND METHODS: One SLA and 1 SLActive dome with an
      internal diameter of 5.0 mm and a height of 3.0 mm were secured to the parietal
      bones of nine 6-month-old male New Zealand rabbits. Three animals were randomly
      euthanized at 4, 7 and 14 days and the newly formed tissues retrieved under the
      domes were analysed with liquid chromatography-mass spectrometry/mass
      spectrometry. STRING and KEGG databases were applied for Gene Ontology and
      pathway analyses. RESULTS: A different modulation of several pathways was
      detected between the 2 groups at all healing times. The main differences in the
      osseous healing response associated to the 2 surfaces were related to pathways
      involved in regulating the inflammatory response, differentiation of osteoblast
      precursors and skeletogenesis. At day 7, the highest number of proteins and the
      highest cellular activity were observed in both groups, although a more complex
      and articulated proteome in terms of cellular metabolism and signal transduction
      was observed in SLActive samples. CONCLUSION: This is the first study describing
      the proteome expressed during early healing stages of guided bone regeneration
      and osseointegration. A combination of enhanced early osteogenic response and
      reduced inflammatory response were suggested for the hydrophilic group. Future
      studies are needed to corroborate these findings and explore the molecular
      effects of different titanium surfaces on the cascade of events taking place
      during bone formation.

PMID- 29063587
TI  - Carbon dioxide and submersed macrophytes in lakes: linking functional ecology to
      community composition.
AB  - Evaluating plant community response to atmospheric CO2 rise is critical to
      predicting ecosystem level change. Freshwater lakes offer a model system for
      examining CO2 effects as submersed macrophyte species differ greatly in their
      growth responses to CO2 enrichment, and free CO2 concentrations among these
      habitats show a wide range of natural, spatial variation. We determined free CO2
      concentrations in the water column and sediment porewater in littoral zones with
      pH < 6.0 in Adirondack Mountain (New York, USA) lakes, and derived a community
      CO2 responsiveness index (CCRI) based on quantitative sampling of 15 submersed
      macrophyte communities coupled with greenhouse-derived growth responses to CO2
      enrichment of constituent species to test two hypotheses: (1) CCRI, which is
      higher for communities dominated by species with greater growth responses to CO2
      enrichment, is positively correlated to free [CO2 ] in the water column, and (2)
      in natural communities, the percent of sediment CO2 -using species, which are
      relatively unresponsive to CO2 enrichment, is negatively correlated to free [CO2
      ]. A significant positive correlation (P = 0.003) between our physiologically
      based CCRI and the concentration of free CO2 in the water column supported our
      primary hypothesis that sites with higher levels of free CO2 are dominated by
      species with greater growth responses to CO2 enrichment. Our CCRI is also highly
      significantly correlated (P < 0.001) to the first axis scores for the same
      vegetation data from polar ordination. Finally, the relative importance of
      species that use sediment CO2 as a photosynthetic carbon source is significantly
      negatively correlated (P = 0.029) with the concentration of free CO2 in the water
      column. Our results indicate that natural variations in CO2 levels are important
      determinants of submersed macrophyte community composition. Further, we
      demonstrate the utility of a physiologically-based index of community
      composition, our CCRI, as an ecologically valid measure of community response to
      CO2 .

PMID- 29063588
TI  - Optimizing lifetime reproductive output: Intermittent breeding as a tactic for
      females in a long-lived, multiparous mammal.
AB  - In iteroparous species, intermittent breeding is an important life-history tactic
      that can greatly affect animal population growth and viability. Despite its
      importance, few studies have quantified the consequences of breeding pauses on
      lifetime reproductive output, principally because calculating lifetime
      reproductive output requires knowledge of each individual's entire reproductive
      history. This information is extremely difficult to obtain in wild populations.
      We applied novel statistical approaches that account for uncertainty in state
      assessment and individual heterogeneity to an 18-year capture-recapture dataset
      of 6,631 female southern elephant seals from Macquarie Island. We estimated
      survival and breeding probabilities, and investigated the consequences of
      intermittent breeding on lifetime reproductive output. We found consistent
      differences in females' demographic performance between two heterogeneity
      classes. In particular, breeding imbued a high cost on survival in the females
      from the heterogeneity class 2, assumed to be females of lower quality.
      Individual quality also appeared to play a major role in a female's decision to
      skip reproduction with females of poorer quality more likely to skip breeding
      events than females of higher quality. Skipping some breeding events allowed
      females from both heterogeneity classes to increase lifetime reproductive output
      over females that bred annually. However, females of lower quality produced less
      offspring over their lifetime. Intermittent breeding seems to be used by female
      southern elephant seals as a tactic to offset reproductive costs on survival and
      enhance lifetime reproductive output but remains unavoidable and driven by
      individual-specific constraints in some other females.

PMID- 29063590
TI  - The prevalence and concordance of human papillomavirus infection in different
      anogenital sites among men and women in Liuzhou, China: A population-based study.
AB  - Human papillomavirus (HPV) infection is the pathogenesis of anogenital cancers
      and genital warts in both men and women, whereas there is a scarcity of large
      studies focused on HPV prevalence in different anogenital sites of both sexes in
      the same population. From May to July 2014, 2,309 men and 2,378 women aged 18-55
      were enrolled from communities in Liuzhou, China. Penis/glans penis/coronary
      sulcus (PGC) and perianal/anal canal (PA) specimens of men, and vaginal (VA),
      vulvar (VU) and PA specimens of women, were collected and genotyped for HPV. The
      prevalence of any HPV tested in PGC and PA samples from men and VA, VU and PA
      samples from women was 10.8%, 3.8%, 14.2%, 13.3% and 8.4%, respectively. The
      concordance of VA and VU was highest (kappa = 0.74), followed by VU and PA
      (0.44), VA and PA (0.38) and PGC and PA (0.14). Besides sex behavior, ever having
      used a towel supplied by a hotel was a risk factor for both external genital and
      PA HPV infection. Our data indicated that women were more of a major reservoir
      for oncogenic HPV infection of both genital sites and PA sites than was men. In
      both sexes, the genital sites were more likely than PA sites to harbor HPV
      infection. The concordance rates of HPV infection between genital sites and PA
      infection were poor.

PMID- 29063589
TI  - Endometrial carcinoma recurrence according to race and ethnicity: An NRG
      Oncology/Gynecologic Oncology Group 210 Study.
AB  - Non-Hispanic black (NHB) women are more likely to experience an endometrial
      carcinoma (EC) recurrence compared to non-Hispanic white (NHW) women. The extent
      to which tumor characteristics, socioeconomic status (SES) and treatment
      contribute to this observation is not well defined. In the NRG
      Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations
      between race/ethnicity and EC recurrence according to tumor characteristics with
      adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB
      and 232 Hispanic women with EC. Recurrence was documented during follow-up. We
      used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals
      (CIs) for associations between race/ethnicity and EC recurrence in models
      stratified by histologic subtype (low-grade endometrioid, high-grade
      endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II,
      III) and adjusted for age, SES, body mass index, smoking status and treatment. In
      histologic subtype-stratified models, higher EC recurrence was noted in NHB women
      with low-grade endometrioid (HR = 1.94, 95% CI = 1.21-3.10) or carcinosarcomas
      (HR = 1.66, 95% CI = 0.99-2.79) compared to NHWs. In stage-stratified models,
      higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI =
      1.06-2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11
      2.95). Our observations of higher EC recurrence risk among NHB and Hispanic
      women, as compared to NHW women, were not explained by tumor characteristics,
      SES, treatment or other confounders. Other factors, such as racial differences in
      tumor biology or other patient factors, should be explored as contributors to
      racial disparities in EC recurrence.

PMID- 29063592
TI  - Omega-3 supplementation associated with improved parent-rated executive function
      in youth with mood disorders: secondary analyses of the omega 3 and therapy
      (OATS) trials.
AB  - BACKGROUND: Improvements in executive functioning (EF) may lead to improved
      quality of life and lessened functional impairment for children with mood
      disorders. The aim was to assess the impact of omega-3 supplementation (Omega3)
      and psychoeducational psychotherapy (PEP), each alone and in combination, on EF
      in youth with mood disorders. We completed secondary analyses of two randomized
      controlled trials (RCTs) of Omega3 and PEP for children with depression and
      bipolar disorder. METHODS: Ninety-five youths with depression or bipolar disorder
      not otherwise specified/cyclothymic disorder were randomized in 12-week RCTs. Two
      capsules (Omega3 or placebo) were given twice daily (1.87 g Omega3 total daily,
      mostly eicosapentaenoic acid). Families randomized to PEP participated in twice
      weekly 50-min sessions. Analyses assess impact of interventions on the Behavior
      Rating Inventory of Executive Functioning (BRIEF) parent-report Global Executive
      Composite (GEC) and two subscales, Behavior Regulation (BRI) and Metacognition
      (MI) Indices. Intent-to-treat repeated measures ANOVAs, using multiple imputation
      for missing data, included all 95 randomized participants. Trials were registered
      with www.clinicaltrials.gov, NCT01341925 & NCT01507753. RESULTS: Participants
      receiving Omega3 (aggregating combined and monotherapy) improved significantly
      more than aggregated placebo on GEC (p = .001, d = .70), BRI (p = .004, d = .49),
      and MI (p = .04, d = .41). Omega3 alone (d = .49) and combined with PEP (d = .67)
      each surpassed placebo on GEC. Moderation by attention-deficit/hyperactivity
      disorder (ADHD) comorbidity was nonsignificant although those with ADHD showed
      nominally greater gains. PEP monotherapy had negligible effect. CONCLUSIONS:
      Decreased impairment in EF was associated with Omega3 supplementation in youth
      with mood disorders. Research examining causal associations of Omega3, EF, and
      mood symptoms is warranted.

PMID- 29063591
TI  - Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the
      hippocampus.
AB  - Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated
      by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to
      bind and activate the cognate receptor, growth hormone secretagogue receptor type
      1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was
      demonstrated to be widespread in the brain, including the cortex and hippocampus,
      indicating that it has multifaceted functions beyond the regulation of
      metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain,
      outside of the hypothalamus, is not well understood. Here, we report the presence
      of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus.
      GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer
      in the rat and wild-type mouse. This immunoreactivity was not affected by the
      pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation
      of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse
      hippocampus, pointing the possibility that the expression of GHSR1a may be a
      prerequisite for the production of GOAT. Application of fluorescein
      isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal
      slice culture (but not in fixed culture or in the presence of GOAT inhibitors)
      mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting
      that extracellularly applied non-octanoylated ghrelin was acylated by endogenous
      GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our
      results will advance the understanding for the role of endogenous GOAT in the
      hippocampus and facilitate the search for the source of ghrelin that is intrinsic
      to the brain.

PMID- 29063593
TI  - Transmitter receptors reveal segregation of the arcopallium/amygdala complex in
      pigeons (Columba livia).
AB  - At the beginning of the 20th century it was suggested that a complex group of
      nuclei in the avian posterior ventral telencephalon is comparable to the
      mammalian amygdala. Subsequent findings, however, revealed that most of these
      structures share premotor characteristics, while some indeed constitute the avian
      amygdala. These developments resulted in 2004 in a change of nomenclature of
      these nuclei, which from then on were named arcopallial or amygdala nuclei and
      referred to as the arcopallium/amygdala complex. The structural basis for the
      similarities between avian and mammalian arcopallial and amygdala subregions is
      poorly understood. Therefore, we analyzed binding site densities for
      glutamatergic AMPA, NMDA and kainate, GABAergic GABAA , muscarinic M1 , M2 and
      nicotinic acetylcholine (nACh; alpha4 beta2 subtype), noradrenergic alpha1 and
      alpha2 , serotonergic 5-HT1A and dopaminergic D1/5 receptors using quantitative
      in vitro receptor autoradiography combined with a detailed analysis of the cyto-
      and myelo-architecture. Our approach supports a segregation of the pigeon's
      arcopallium/amygdala complex into the following subregions: the arcopallium
      anterius (AA), the arcopallium ventrale (AV), the arcopallium dorsale (AD), the
      arcopallium intermedium (AI), the arcopallium mediale (AM), the arcopallium
      posterius (AP), the nucleus posterioris amygdalopallii pars basalis (PoAb) and
      pars compacta (PoAc), the nucleus taeniae amgygdalae (TnA) and the area
      subpallialis amygdalae (SpA). Some of these subregions showed further subnuclei
      and each region of the arcopallium/amygdala complex are characterized by a
      distinct multi-receptor density expression. Here we provide a new detailed map of
      the pigeon's arcopallium/amygdala complex and compare the receptor architecture
      of the subregions to their possible mammalian counterparts.

PMID- 29063594
TI  - Late (> 7 days) systemic postnatal corticosteroids for prevention of
      bronchopulmonary dysplasia in preterm infants.
AB  - BACKGROUND: Many preterm infants who survive go on to develop bronchopulmonary
      dysplasia, probably as the result of persistent inflammation in the lungs.
      Corticosteroids have powerful anti-inflammatory effects and have been used to
      treat individuals with established bronchopulmonary dysplasia. However, it is
      unclear whether any beneficial effects outweigh the adverse effects of these
      drugs. OBJECTIVES: To examine the relative benefits and adverse effects of late
      systemic postnatal corticosteroid treatment (> 7 days) for preterm infants with
      evolving or established bronchopulmonary dysplasia. SEARCH METHODS: For the 2017
      update, we used the standard search strategy of Cochrane Neonatal to search the
      Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE
      via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21
      February 2017); and the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL; January 2013 to 21 February 2017). We also searched clinical trials
      databases, conference proceedings, and reference lists of retrieved articles for
      randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We
      selected for inclusion in this review randomised controlled trials (RCTs)
      comparing systemic postnatal corticosteroid treatment versus placebo or nothing
      initiated more than seven days after birth for preterm infants with evolving or
      established bronchopulmonary dysplasia. DATA COLLECTION AND ANALYSIS: We used the
      GRADE approach to assess the quality of evidence.We extracted and analysed data
      regarding clinical outcomes including mortality, bronchopulmonary dysplasia,
      death or bronchopulmonary dysplasia, failure to extubate, complications during
      primary hospitalisation, and long-term health outcomes. MAIN RESULTS: Twenty-one
      RCTs enrolling a total of 1424 participants were eligible for this review. All
      were RCTs, but methods used for random allocation were not always clear.
      Allocation concealment, blinding of the intervention, and blinding of outcome
      assessments most often were satisfactory. Late steroid treatment was associated
      with a reduction in neonatal mortality (at 28 days) but no reduction in mortality
      at 36 weeks, at discharge, or at latest reported age. Benefits of delayed steroid
      treatment included reductions in failure to extubate by 3, 7, or 28 days;
      bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual
      age; need for late rescue treatment with dexamethasone; discharge on home oxygen;
      and death or bronchopulmonary dysplasia both at 28 days of life and at 36 weeks'
      postmenstrual age. Data revealed a trend towards increased risk of infection and
      gastrointestinal bleeding but no increase in risk of necrotising enterocolitis.
      Short-term adverse affects included hyperglycaemia, glycosuria, and hypertension.
      Investigators reported an increase in severe retinopathy of prematurity but no
      significant increase in blindness. Trial results showed a trend towards reduction
      in severe intraventricular haemorrhage, but only five studies enrolling 247
      infants reported this outcome. Trends towards an increase in cerebral palsy or
      abnormal neurological examination findings were partly offset by a trend in the
      opposite direction involving death before late follow-up. The combined rate of
      death or cerebral palsy was not significantly different between steroid and
      control groups. Major neurosensory disability and the combined rate of death or
      major neurosensory disability were not significantly different between steroid
      and control groups. There were no substantial differences between groups for
      other outcomes in later childhood, including respiratory health or function,
      blood pressure, or growth, although there were fewer participants with a
      clinically important reduction in forced expired volume in one second (FEV1) on
      respiratory function testing in the dexamethasone group.GRADE findings were high
      for all major outcomes considered, but review authors degraded the quality of
      evidence by one level because we found evidence of publication bias
      (bronchopulmonary dysplasia at 36 weeks). AUTHORS' CONCLUSIONS: Benefits of late
      corticosteroid therapy may not outweigh actual or potential adverse effects. This
      review of postnatal systemic corticosteroid treatment for bronchopulmonary
      dysplasia initiated after seven days of age suggests that late therapy may reduce
      neonatal mortality without significantly increasing the risk of adverse long-term
      neurodevelopmental outcomes. However, the methodological quality of studies
      determining long-term outcomes is limited in some cases (some studies assessed
      surviving children only before school age, when some important neurological
      outcomes cannot be determined with certainty), and no studies were sufficiently
      powered to detect increased rates of important adverse long-term neurosensory
      outcomes. Evidence showing both benefits and harms of treatment and limitations
      of available evidence suggests that it may be prudent to reserve the use of late
      corticosteroids for infants who cannot be weaned from mechanical ventilation, and
      to minimise both dose and duration for any course of treatment.

PMID- 29063595
TI  - Pulmonary anatomy and a case of unilateral aplasia in a common snapping turtle
      (Chelydra serpentina): developmental perspectives on cryptodiran lungs.
AB  - The common snapping turtle (Chelydra serpentina) is a well studied and broadly
      distributed member of Testudines; however, very little is known concerning
      developmental anomalies and soft tissue pathologies of turtles and other
      reptiles. Here, we present an unusual case of unilateral pulmonary aplasia,
      asymmetrical carapacial kyphosis, and mild scoliosis in a live adult C.
      serpentina. The detailed three-dimensional (3D) anatomy of the respiratory system
      in both the pathological and normal adult C. serpentina, and a hatchling are
      visualized using computed tomography (CT), microCT, and 3D digital anatomical
      models. In the pathological turtle, the right lung consists of an extrapulmonary
      bronchus that terminates in a blind stump with no lung present. The left lung is
      hyperinflated relative to the normal adult, occupying the extra coelomic space
      facilitated by the unusual mid-carapacial kyphotic bulge. The bronchial tree of
      the left lung retains the overall bauplan of the normal specimens, with some
      minor downstream variation in the number of secondary airways. The primary
      difference between the internal pulmonary structure of the pathological
      individual and that of a normal adult is a marked increase in the surface area
      and density of the parenchymal tissue originating from the secondary airways, a
      14.3% increase in the surface area to volume ratio. Despite this, the aplasia has
      not had an impact upon the ability of the turtle to survive; however, it did
      interfere with aquatic locomotion and buoyancy control under water. This turtle
      represents a striking example of a non-fatal congenital defect and compensatory
      visceral hypertrophy.

PMID- 29063597
TI  - Patterning spinal nerves and vertebral bones.
AB  - A prominent anatomical feature of the peripheral nervous system is the
      segmentation of mixed (motor, sensory and autonomic) spinal nerves alongside the
      spinal cord. During early development their axon growth cones avoid the
      developing vertebral elements by traversing the anterior/cranial half of each
      somite-derived sclerotome, so ensuring the separation of spinal nerves from
      vertebral bones as axons extend towards their peripheral targets. A glycoprotein
      expressed on the surface of posterior half-sclerotome cells confines growth cones
      to the anterior half-sclerotomes by contact repulsion. A closely similar
      glycoprotein is expressed in avian and mammalian grey matter, where we
      hypothesize it may have evolved to regulate neural plasticity in birds and
      mammals.

PMID- 29063596
TI  - Ca2+ -dependent down-regulation of human histamine H1 receptors in Chinese
      hamster ovary cells.
AB  - Gq/11 protein-coupled human histamine H1 receptors in Chinese hamster ovary cells
      stimulated with histamine undergo clathrin-dependent endocytosis followed by
      proteasome/lysosome-mediated down-regulation. In this study, we evaluated the
      effects of a sustained increase in intracellular Ca2+ concentrations induced by a
      receptor-bypassed stimulation with ionomycin, a Ca2+ ionophore, on the
      endocytosis and down-regulation of H1 receptors in Chinese hamster ovary cells.
      All cellular and cell-surface H1 receptors were detected by the binding of [3
      H]mepyramine to intact cells sensitive to the hydrophobic and hydrophilic H1
      receptor ligands, mepyramine and pirdonium, respectively. The pretreatment of
      cells with ionomycin markedly reduced the mepyramine- and pirdonium-sensitive
      binding sites of [3 H]mepyramine, which were completely abrogated by the
      deprivation of extracellular Ca2+ and partially by a ubiquitin-activating enzyme
      inhibitor (UBEI-41), but were not affected by inhibitors of calmodulin (W-7 or
      calmidazolium) and protein kinase C (chelerythrine or GF109203X). These ionomycin
      induced changes were also not affected by inhibitors of receptor endocytosis via
      clathrin (hypertonic sucrose) and caveolae/lipid rafts (filipin or nystatin) or
      by inhibitors of lysosomes (E-64, leupeptin, chloroquine, or NH4 Cl), proteasomes
      (lactacystin or MG-132), and a Ca2+ -dependent non-lysosomal cysteine protease
      (calpain) (MDL28170). Since H1 receptors were normally detected by confocal
      immunofluorescence microscopy with an antibody against H1 receptors, even after
      the ionomycin treatment, H1 receptors appeared to exist in a form to which [3
      H]mepyramine was unable to bind. These results suggest that H1 receptors are
      apparently down-regulated by a sustained increase in intracellular Ca2+
      concentrations with no process of endocytosis and lysosomal/proteasomal
      degradation of receptors.

PMID- 29063598
TI  - Insertion methods comparison for The Streamlined Liner of the Pharynx Airway in
      children by novice.
AB  - BACKGROUND: The Streamlined Liner of the Pharynx Airway (SLIPATM) is a popular
      supraglottic airway device used for pediatric anesthesia. However, based on the
      anatomical features of pediatric patients, novice residents are expected to have
      difficulties inserting the device. The objective of this work was to improve the
      SLIPA insertion by modifying the device. METHODS: A total of 134 children were
      randomized into two groups. Anesthesia was standardized among all patients except
      for the way in which the SLIPA was inserted. One group underwent the conventional
      method of insertion (Group C), while the modified group received a SLIPA that was
      bent120 degrees  at the 'bridge' point with an intubating stylet (Group M). The
      primary outcome was insertion success rate, and the secondary outcomes included
      insertion time, incidence of complications and hemodynamic responses to
      insertion. RESULTS: The insertion success rate was significantly higher in Group
      M than Group C (94% vs. 73%, Chi2 = 10.659, P = 0.001). The insertion time for
      Group M [29.31 (25.91-35.60) seconds] was shorter than for Group C [34.72 (26.81
      42.58) seconds] (Z = -2.381, P = 0.017). Trends in heart rate (F = 0.260, P =
      0.794), mean blood pressure (F = 0.167, P = 0.683) did not significantly differ
      between the two groups over time. In terms of complications, we found no
      significant differences between groups (P > 0.05). CONCLUSION: The 120 degrees 
      bend improved SLIPA insertion when performed by novice, as reflected by higher
      insertion success rates and shorter insertion times, with no statistical
      differences in hemodynamic response to insertion or the incidence rates of
      complications between the two groups.

PMID- 29063600
TI  - Practicing for the Future: Deliberate Practice in Early Childhood.
AB  - Deliberate practice is essential for acquiring a wide range of skills that have
      been central to humans' adaptive success, yet little is known about when and how
      children develop this capability. The current study examined 4- to 7-year-olds'
      (N = 120) ability to selectively practice a skill that would be useful in the
      near future, as well as their broader understanding of the role of deliberate
      practice in skill acquisition. Six- and 7-year-olds demonstrated both an explicit
      understanding of deliberate practice and the capacity to practice without being
      prompted. Five-year-olds showed an understanding of deliberate practice and some
      capacity to practice, whereas 4-year-olds showed neither of these capabilities.
      Findings reveal important developments in children's future-directed behavior
      beyond the preschool years.

PMID- 29063599
TI  - Observation and determination of periodontal tissue profile using optical
      coherence tomography.
AB  - BACKGROUND AND OBJECTIVE: Diagnosis is a crucial step in periodontal treatment.
      The aim of this study was to evaluate the effectiveness of optical coherence
      tomography (OCT) for observation and determination of periodontal tissue profiles
      in vivo. MATERIAL AND METHODS: In experiment 1, refractive indices of purified
      water, porcine gingiva and human gingiva at 1330 nm were determined for the
      analysis of OCT images of periodontal tissues. In experiment 2, OCT examination
      was performed in the midlabial apico-coronal plane of mandibular anteriors in 30
      Asian volunteers with healthy gingiva. Sulcus depth was measured on intra-oral
      photographs taken during probing. In the OCT images, the gingival, epithelial and
      connective tissue thickness, and the position of alveolar bone crest were
      determined and finally, the biologic width was measured. RESULTS: Refractive
      indices of purified water, porcine gingiva and human gingiva were 1.335, 1.393
      and 1.397, respectively. Cross-sectional images of gingival epithelium,
      connective tissue and alveolar bone were depicted in real-time. The sulcular and
      junctional epithelium could be visualized occasionally. Laser penetration and
      reflection were limited to a certain depth with an approximate maximal imaging
      depth capability of 1.5 mm and OCT images of the periodontal structure were not
      clear in some cases. The average maximal thickness of gingiva and epithelium and
      biologic width at the mandibular anteriors were 1.06 +/- 0.21, 0.49 +/- 0.15 and
      2.09 +/- 0.60 mm, respectively. CONCLUSION: OCT has promise for non-invasive
      observation of the periodontal tissue profile in detail and measurement of
      internal periodontal structures including biologic width in the anterior region.

PMID- 29063601
TI  - Community-Based Palliative Care and Advance Care Planning Documentation: Evidence
      from a Multispecialty Group.
AB  - BACKGROUND/OBJECTIVES: With the growing public demand for access to critical
      health data across care settings, it is essential that advance care planning
      (ACP) information be included in the electronic health record (EHR) so that
      multiple clinicians can access it and understand individuals' preferences for end
      of-life care. Community-based palliative care programs often incorporate ACP
      services. This study examined whether a community-based palliative care program
      is associated with digitally extractable ACP documentation in the EHR. DESIGN:
      Observational study using propensity score-weighted generalized estimation
      equations to examine patterns of digitally extractable ACP documentation.
      SETTING: Palo Alto Medical Foundation (PAMF), a multispecialty ambulatory
      healthcare system in northern California. PARTICIPANTS: Individuals aged 65 and
      older with serious illnesses between January 1, 2013, and December 31, 2014 (N =
      3,444). INTERVENTION: Community-based palliative care program in PAMF.
      MEASUREMENTS: Digitally extractable ACP in EHR. RESULTS: We found that only 14%
      (n = 483) of individuals with serious illnesses had digitally extractable ACP in
      electronic health records. Of the 6% of individuals receiving palliative care,
      65% had ACP, versus 11% of those not receiving palliative care. Study results
      showed a strong positive association between palliative care and ACP. CONCLUSION:
      Only a small percentage of individuals with serious illnesses had ACP
      documentation in the EHR. Individuals with serious illnesses infrequently used
      palliative care delivered by board-certified palliative care specialists.
      Palliative care service use was associated with higher rates of ACP after
      controlling for organizational and individual characteristics using a propensity
      score weighting method. Scalable interventions targeted at non-palliative care
      clinicians for universal access to ACP are needed.

PMID- 29063604
TI  - Obituary: Professor Mike Benjamin (1948-2017).

PMID- 29063602
TI  - Inhibitory neuron-specific Cre-dependent red fluorescent labeling using VGAT BAC
      based transgenic mouse lines with identified transgene integration sites.
AB  - Inhibitory neurons are crucial for shaping and regulating the dynamics of the
      entire network, and disturbances in these neurons contribute to brain disorders.
      Despite the recent progress in genetic labeling techniques, the heterogeneity of
      inhibitory neurons requires the development of highly characterized tools that
      allow accurate, convenient, and versatile visualization of inhibitory neurons in
      the mouse brain. Here, we report a novel genetic technique to visualize the vast
      majority and/or sparse subsets of inhibitory neurons in the mouse brain without
      using techniques that require advanced skills. We developed several lines of Cre
      dependent tdTomato reporter mice based on the vesicular GABA transporter (VGAT)
      BAC, named VGAT-stop-tdTomato mice. The most useful line (line #54) was selected
      for further analysis based on two characteristics: the inhibitory neuron
      specificity of tdTomato expression and the transgene integration site, which
      confers efficient breeding and fewer adverse effects resulting from transgene
      integration-related genomic disruption. Robust and inhibitory neuron-specific
      expression of tdTomato was observed in a wide range of developmental and cellular
      contexts. By breeding the VGAT-stop-tdTomato mouse (line #54) with a novel Cre
      driver mouse line, Galntl4-CreER, sparse labeling of inhibitory neurons was
      achieved following tamoxifen administration. Furthermore, another interesting
      line (line #58) was generated through the unexpected integration of the transgene
      into the X-chromosome and will be used to map X-chromosome inactivation of
      inhibitory neurons. Taken together, our studies provide new, well-characterized
      tools with which multiple aspects of inhibitory neurons can be studied in the
      mouse.

PMID- 29063603
TI  - Effects of paraoxonase 1 on the cytodifferentiation and mineralization of
      periodontal ligament cells.
AB  - BACKGROUND AND OBJECTIVE: Single nucleotide polymorphisms (SNPs) of paraoxonase 1
      (PON1) are known to be associated with the pathogenesis of osteoporosis and
      periodontitis. However, the effects of PON1 on the osteoblastic differentiation
      of periodontal ligament (PDL) cells are unclear. In this study, we examined the
      effects of PON1 on the osteoblastic differentiation of PDL cells, and analysed
      the role of PON1 SNPs on the pathogenesis of aggressive periodontitis (AgP) in
      the Japanese population. MATERIAL AND METHODS: Human PDL (HPDL) cells were
      exposed to the PON1 plasmid and PON1 inhibitor, 2-hydroxyquinoline, and cultured
      in mineralization medium. Expression of calcification-related genes and calcified
      nodule formation were assessed by real-time PCR, an alkaline phosphatase (ALPase)
      activity assay and Alizarin red staining. Sanger sequencing was performed to
      evaluate whether PON1 SNPs are associated with the pathogenesis of AgP in
      Japanese people. RESULTS: During osteoblastic differentiation of HPDL cells,
      expression of PON1 mRNA increased in a time-dependent manner. PON1 stimulated an
      increase in expression of mRNA for calcification-related genes, as well as ALPase
      activity. In contrast, 2-hydroxyquinoline clearly inhibited the expression of
      calcification-related genes, ALPase activity and calcified nodule formation in
      HPDL cells. Moreover, there was a statistically significant difference in the
      minor allele frequency of PON1 SNP rs854560 between the Japanese control database
      and patients with AgP in the Japanese population (P = .0190). CONCLUSION: PON1
      induced cytodifferentiation and mineralization of HPDL cells, and PON1 SNP
      rs854560 may be associated with the pathogenesis of AgP in the Japanese
      population.

PMID- 29063605
TI  - Disturbance of verticality perception and postural dysfunction in Parkinson's
      disease.
AB  - OBJECTIVES: Verticality perception is known to be abnormal in Parkinson's disease
      (PD), but in which stage respective dysfunctions arise and how they relate to
      postural disorders remains to be settled. These issues were studied with respect
      to different dimensions of the subjective visual vertical (SVV) in relation to
      clinical parameters of postural control. MATERIALS & METHODS: All participants
      had to orientate a luminous line at random planar orientations to a strictly
      vertical position using an automated operator system. The SVV was analyzed in 58
      PD patients and 28 control subjects with respect to (i) the angle between true
      and subjective vertical (deviation) and (ii) the variability of this across five
      measurements (variability). Results were referred to the subjective upright head
      position (SUH), the disease stage, and clinical gait/balance features assessed by
      the MDS-UPDRS and the Tinetti test. RESULTS: Parkinson's disease patients had
      significantly higher SVV deviation and variability than controls. With respect to
      disease stage, deviation developed before abnormal variability. SVV variability
      was associated with poor balance and gait performance, as well as postural
      instability. Deficits in SUH and SVV deviation were correlated and mostly
      unidirectional, but did not correspond to the side of motor symptom dominance.
      CONCLUSIONS: Visual verticality perception in PD is deviated already in early
      stages, conceivably as a relatively static internal misrepresentation of object
      orientation. Variability about verticality perception emerges in more advanced
      stages and is associated with postural and balance abnormalities.

PMID- 29063606
TI  - Harnessing Meta-analysis to Refine an Oncology Patient Population for Physiology
      Based Pharmacokinetic Modeling of Drugs.
AB  - Certain oncology compounds exhibit fundamental pharmacokinetic (PK) disparities
      between healthy and malignant conditions. Given the effects of tumor-associated
      inflammation on enzyme and transporter expression, we performed a meta-analysis
      of CYP- and transporter-sensitive substrate clinical PK to quantitatively compare
      enzyme and transporter abundances between healthy volunteers (HV) and cancer
      patients (CP). Hepatic and intestinal CYP1A2, CYP2C19, and CYP3A4 abundance were
      subsequently adjusted via Simcyp's sensitivity analysis tool. Of the 11
      substrates we investigated, seven displayed marked exposure differences >1.25
      fold between CP and HV. Although CP studies are limited, meta-analysis-based
      reduction in CYP1A2, CYP2C19, and CYP3A4 enzyme abundances in a virtual oncology
      population effectively captures CP-PK for caffeine, theophylline, midazolam,
      simvastatin, omeprazole, and a subset of oncology compounds. These changes allow
      extrapolation from HV to CP, enhancing predictive capability; therefore,
      conducting simulations in this CYP-modified oncology (MOD-CP) population provides
      a more relevant characterization of CP-PK.

PMID- 29063607
TI  - Spinal or general anaesthesia for lower-limb amputation in peripheral artery
      disease - a retrospective cohort study.
AB  - BACKGROUND: The present study aimed to determine which method of anaesthesia
      (spinal anaesthesia or general anaesthesia) is better in reducing post-operative
      analgesic requirements in patients undergoing major limb amputation for lower
      limb ischaemia. Another aim was to find out if anaesthesiologists use neuraxial
      anaesthesia in high-risk patients despite abnormal coagulation profile or use of
      anticoagulation. METHODS: The study was a retrospective cohort study. All
      patients undergone above-the-knee amputation or below-the-knee amputation due to
      peripheral artery disease between 1996 and 2010 were reviewed to evaluate post
      operative opioid consumption and complications. RESULTS: A total of 434
      amputations in 323 patients were included in the study. The number of surgical
      complications, the need for surgical revision and the number of intensive care
      unit admissions were significantly higher in the general anaesthesia group. The
      need for post-operative opioid medication was significantly lower in patients
      with above-the-knee amputation and spinal anaesthesia. The use of post-operative
      epidural analgesia did not reduce analgesic requirements. In the present study,
      there were patients who received neuraxial anaesthesia despite abnormal
      coagulation profile or uninterrupted warfarin or clopidogrel. There were no
      reported cases of spinal or epidural haematoma. CONCLUSION: Patients with spinal
      anaesthesia had a lower rate of surgical complications, re-operations and
      intensive care unit admissions. Patients with above-the-knee amputation and
      spinal anaesthesia had a lesser need for opioid medication in the post-operative
      period than patients with general anaesthesia. Anaesthesiologists performed
      neuraxial anaesthesia and/or analgesia in high-risk patients despite abnormal
      coagulation profile or ongoing anticoagulation, but no adverse outcomes were
      reported.

PMID- 29063608
TI  - Parental Autonomy Support in Two Cultures: The Moderating Effects of Adolescents'
      Self-Construals.
AB  - Parental autonomy support has been related to positive adolescent outcomes,
      however, its relation to outcomes in collectivist cultural groups is unclear.
      This study examined relations of specific autonomy supportive behaviors and
      outcomes among 401 adolescents (Mage  = 12.87) from the United States (N = 245)
      and collectivist-oriented Ghana (N = 156). It also examined whether adolescents'
      self-construals moderated the relations of specific types of autonomy support
      with outcomes. Factor analyses indicated two types of autonomy support:
      perspective taking/open exchange and allowance of decision making/choice. In both
      countries, perspective taking/open exchange predicted positive outcomes, but
      decision making/choice only did so in the United States. With regard to
      moderation, the more independent adolescents' self-construals, the stronger the
      relations of decision making/choice to parental controllingness and school
      engagement.

PMID- 29063610
TI  - Erratum.

PMID- 29063611
TI  - Erratum.

PMID- 29063609
TI  - Integrated genome analysis of uterine leiomyosarcoma to identify novel driver
      genes and targetable pathways.
AB  - Uterine leiomyosarcomas (uLMS) are rare, aggressive malignancies for which
      limited treatment options are available. To gain novel molecular insights into
      uLMS and identify potential novel therapeutic targets, we characterized 84 uLMS
      samples for genome-wide somatic copy number alterations, mutations, gene fusions
      and gene expression and performed a data integration analysis. We found that
      alterations affecting TP53, RB1, PTEN, MED12, YWHAE and VIPR2 were present in the
      majority of uLMS. Pathway analyses additionally revealed that the PI3K/AKT/mTOR,
      estrogen-mediated S-phase entry and DNA damage response signaling pathways, for
      which inhibitors have already been developed and approved, frequently harbored
      genetic changes. Furthermore, a significant proportion of uLMS was characterized
      by amplifications and overexpression of known oncogenes (CCNE1, TDO2), as well as
      deletions and reduced expression of tumor suppressor genes (PTEN, PRDM16).
      Overall, it emerged that the most frequently affected gene in our uLMS samples
      was VIPR2 (96%). Interestingly, VIPR2 deletion also correlated with unfavorable
      survival in uLMS patients (multivariate analysis; HR = 4.5, CI = 1.4-14.3, p =
      1.2E-02), while VIPR2 protein expression was reduced in uLMS vs. normal
      myometrium. Moreover, stimulation of VIPR2 with its natural agonist VIP decreased
      SK-UT-1 uLMS cell proliferation in a dose-dependent manner. These data suggest
      that VIPR2, which is a negative regulator of smooth muscle cell proliferation,
      might be a novel tumor suppressor gene in uLMS. Our work further highlights the
      importance of integrative molecular analyses, through which we were able to
      uncover the genes and pathways most frequently affected by somatic alterations in
      uLMS.

PMID- 29063612
TI  - Endothelial tubes: another window into lymphatic function.

PMID- 29063613
TI  - Interactive Effects of Maternal Alcohol Problems and Parental Separation on
      Timing of Daughter's First Drink.
AB  - BACKGROUND: Few studies examine risk to offspring who experience both parental
      alcohol problems and parental separation and still fewer consider gender of the
      affected parent. We examined interactive effects of maternal versus paternal
      alcohol problems and parental separation on timing of first alcoholic drink in
      daughters. METHODS: Data were drawn from a sample of 3,539 European (or other)
      ancestry (EA) and 611 African ancestry (AA) female twins born between 1975 and
      1985, median age 15 at first assessment. Cox proportional hazards regression
      models were estimated predicting age at first full drink from parental history of
      alcohol problems (mother only, father only, or both parents), parental separation
      during childhood, and the interaction of parental alcohol problems and parental
      separation. Cox models were estimated without and with adjustment for correlated
      risk factors, separately for EA and AA twins. RESULTS: For both EA and AA twins,
      a significant interaction between parental separation and mother-only alcohol
      problems was observed, suggesting reduced risk of drinking associated with mother
      only alcohol problems in separated versus intact families. CONCLUSIONS: Findings
      highlight parental separation as an important moderator of risk to children of
      mothers who have a history of problem drinking, with interactive effects observed
      consistently across racial group. To identify underlying processes, additional
      research is needed with more detailed characterization of separated families
      where mother only has a history of alcohol problems.

PMID- 29063615
TI  - Regression analysis of interval-censored failure time data with possibly crossing
      hazards.
AB  - Interval-censored failure time data occur in many areas, especially in medical
      follow-up studies such as clinical trials, and in consequence, many methods have
      been developed for the problem. However, most of the existing approaches cannot
      deal with the situations where the hazard functions may cross each other. To
      address this, we develop a sieve maximum likelihood estimation procedure with the
      application of the short-term and long-term hazard ratio model. In the method,
      the I-splines are used to approximate the underlying unknown function. An
      extensive simulation study was conducted for the assessment of the finite sample
      properties of the presented procedure and suggests that the method seems to work
      well for practical situations. The analysis of an motivated example is also
      provided.

PMID- 29063614
TI  - Meta-Analyses of Externalizing Disorders: Genetics or Prenatal Alcohol Exposure?
AB  - BACKGROUND: Externalizing disorders are heritable precursors to alcohol
      dependence, common in children of alcoholics (COA), and in children with prenatal
      alcohol exposure (PAE). Pregnancies involving alcohol exposure sufficient to
      affect the fetus may involve women with genetic risk for alcohol dependence. We
      hypothesized that known PAE will increase the odds of having an externalizing
      disorder compared to COA. METHODS: The odds ratios of 3 externalizing disorders
      (attention-deficit hyperactivity disorder [ADHD], conduct disorder [CD], and
      oppositional defiant disorder [ODD]) were obtained for 2 domains: (i) PAE and
      (ii) COA, by estimating the logged odds ratio (LOR) for each study. Permutation
      tests were implemented to compare LORs for PAE versus COA studies within each
      disorder, including PAE versus an alcohol dependent (AD) mother and PAE versus an
      AD father. RESULTS: In PAE studies, the odds of ADHD and CD were elevated. Rates
      of all 3 disorders were elevated in COA studies. Permutation tests revealed that
      the mean LOR for ADHD was significantly higher in PAE studies compared to: COA (p
      = 0.01), AD mother (p < 0.05), and AD father (p = 0.03). No differences were
      found for ODD (p = 0.09) or CD (p = 0.21). CONCLUSIONS: These results provide
      compelling evidence of an increased risk of ADHD in those with PAE beyond that
      due to parental alcohol dependence or a genetic liability, consistent with a
      unique etiology most likely due to direct alcohol exposure during prenatal
      development.

PMID- 29063616
TI  - Genetic association studies and the risk factors for developing the "Immuno-bile
      logic" disease primary biliary cholangitis.

PMID- 29063617
TI  - Ivermectin and its target molecules: shared and unique modulation mechanisms of
      ion channels and receptors by ivermectin.
AB  - Ivermectin (IVM) is an antiparasitic drug that is used worldwide and rescues
      hundreds of millions of people from onchocerciasis and lymphatic filariasis. It
      was discovered by Satoshi Omura and William C. Campbell, to whom the 2015 Nobel
      Prize in Physiology or Medicine was awarded. It kills parasites by activating
      glutamate-gated Cl- channels, and it also targets several ligand-gated ion
      channels and receptors, including Cys-loop receptors, P2X4 receptors and
      fernesoid X receptors. Recently, we found that IVM also activates a novel target,
      the G-protein-gated inwardly rectifying K+ channel, and also identified the
      structural determinant for the activation. In this review, we aim to provide an
      update and summary of recent progress in the identification of IVM targets, as
      well as their modulation mechanisms, through molecular structures, chimeras and
      site-directed mutagenesis, and molecular docking and modelling studies.

PMID- 29063618
TI  - Vulnerability of employees in businesses with fewer than five workers (micro
      enterprises) to occupational safety and health problems.
AB  - INTRODUCTION: We assessed the characteristics of micro-enterprises (businesses
      with fewer than five workers) focusing on occupational safety and health (OSH)
      issues. METHODS: We performed a secondary analysis of data from the Economically
      Active Population Supplementary Survey and the fourth Korean Working Conditions
      Survey of 2014. RESULTS: Relative to larger businesses, micro-enterprises employ
      more women, temporary workers, and older workers (>55 years). In addition, more
      workers in micro-enterprises held "elementary occupations" (unskilled or under
      skilled) or "sales and service jobs." Key sectors of such employment included the
      sectors of "wholesale and retail trade" and "hotel and restaurants." Furthermore,
      lower skilled workers in such micro-enterprises more frequently reported exposure
      to ergonomic risk factors and subsequent musculoskeletal disorders, and they also
      experienced a much higher fatality rate due to occupational injuries. CONCLUSION:
      Our results indicate that Korean workers in micro-enterprises are more vulnerable
      to OSH problems than workers in larger businesses.

PMID- 29063619
TI  - Effect of an acute moderate-exercise session on metabolic and inflammatory
      profile of PPAR-alpha knockout mice.
AB  - : Peroxisome proliferator-activated receptors (PPARs) play a major role in
      metabolism and inflammatory control. Exercise can modulate PPAR expression in
      skeletal muscle, adipose tissue, and macrophages. Little is known about the
      effects of PPAR-alpha in metabolic profile and cytokine secretion after acute
      exercise in macrophages. In this context, the aim of this study was to understand
      the influence of PPAR-alpha on exercise-mediated immune metabolic parameters in
      peritoneal macrophages. Mice C57BL/6 (WT) and PPAR-alpha knockout (KO) were
      examined in non-exercising control (n = 4) or 24 hours after acute moderate
      exercise (n = 8). Metabolic parameters (glucose, non-esterified fatty acids,
      total cholesterol [TC], and triacylglycerol [TG]) were assessed in serum.
      Cytokine concentrations (IL-1beta, IL-6, IL-10, TNF-alpha, and MCP-1) were
      measured from peritoneal macrophages cultured or not with LPS (2.5 MUg/mL) and
      Rosiglitazone (1 MUM). Exercised KO mice exhibited low glucose concentration and
      higher TC and TG in serum. At baseline, no difference in cytokine production
      between the genotypes was observed. However, IL-1beta was significantly higher in
      KO mice after LPS stimulus. IL-6 and IL-1beta had increased concentrations in KO
      compared with WT, even after exercise. MCP-1 was not restored in exercised KO LPS
      group. Rosiglitazone was not able to reduce proinflammatory cytokine production
      in KO mice at baseline level or associated with exercise. Acute exercise did not
      alter mRNA expression in WT mice. CONCLUSION: PPAR-alpha seems to be needed for
      metabolic glucose homeostasis and anti-inflammatory effect of acute exercise. Its
      absence may induce over-expression of pro-inflammatory cytokines in LPS stimulus.
      Moreover, moderate exercise or PPAR-gamma agonist did not reverse this response.

PMID- 29063620
TI  - Predictive value of epithelial-mesenchymal-transition (EMT) signature and PARP-1
      in prostate cancer radioresistance.
AB  - INTRODUCTION: Epithelial-mesenchymal-transition (EMT) has been previously
      identified as a contributor to prostate cancer progression to metastasis and
      therapeutic resistance to antiandrogens and radiotherapy. In this study we
      conducted a retrospective analysis to investigate the significance of radiation
      induced EMT and consequential changes to the tumor microenvironment in
      biochemical recurrence and response to radiotherapy in prostate cancer patients.
      METHODS: Expression profiling and localization for EMT effectors, E-Cadherin, N
      Cadherin, beta-catenin and Vimentin was assessed in human prostate tumor
      specimens pre- and post-radiotherapy and correlated with biochemical recurrence.
      In addition, immunoreactivity of the DNA repair enzyme, polymerase (PARP-1) and
      the cytoskeletal-remodeling regulator, cofilin was evaluated in prostate tumor
      specimens pre- and post-radiotherapy and correlated with pre-treatment prostate
      specific antigen levels (PSA). RESULTS: Our findings identified that
      characteristic changes associated with the EMT phenotype and its reversal to
      mesenchymal-epithelial-transition (MET) within the tumor microenvironment
      correlate with biochemical recurrence and resistance to radiotherapy among
      prostate cancer patients. Moreover, elevated PARP-1 expression among the tumor
      cells undergoing EMT implicates that DNA repair mechanisms may potentially
      reverse the cytotoxic effects of radiotherapy-induced DNA breaks. CONCLUSIONS:
      Our results suggest that EMT programming effectors, integrated with the actin
      cytoskeleton regulator cofilin and mesenchymal PARP-1 expression profile provide
      a signature of potential predictive significance of therapeutic response to
      radiotherapy in a subset of prostate cancer patients.

PMID- 29063621
TI  - Impetigo: A need for new therapies in a world of increasing antimicrobial
      resistance.
AB  - WHAT IS KNOWN AND OBJECTIVE: Impetigo is a highly contagious bacterial skin
      infection and is one of the most common skin infections in children. Antibiotics
      are the first-line treatment when multiple lesions exist, but with an increasing
      prevalence of antibiotic-resistant bacteria the successful management of impetigo
      in the future is an area of concern. COMMENT: Current treatment options that
      favour the use of oral antibiotic therapy are increasingly problematic.
      Widespread use of these agents contributes to antimicrobial resistance and has
      adverse consequences for individuals and communities. There is a need for new
      topical antimicrobials and antiseptics as an alternative treatment strategy. WHAT
      IS NEW AND CONCLUSION: To successfully treat impetigo into the future and ensure
      that therapy does not contribute to bacterial resistance, additional research is
      required to ascertain the usefulness of alternative agents, including new topical
      antimicrobials and antiseptics.

PMID- 29063623
TI  - Cooling muscles following exercise.

PMID- 29063622
TI  - Effect of menstrual cycle phase and hormonal treatments on evaluation of tubal
      patency in baboons.
AB  - BACKGROUND: We evaluated whether menstrual cycle phase influences the assessment
      of tubal patency by hysterosalpingography (HSG) in baboons. METHODS:
      Retrospective analysis of baseline tubal patency studies and serum estradiol (E2
      ) and progesterone (P4) values obtained from female baboons used as models for
      development of non-surgical permanent contraception in women. The main outcome
      measure was bilateral tubal patency (BTP) in relationship with estradiol level.
      RESULTS: Female baboons (n = 110) underwent a single (n = 81), two (n = 26), or
      three (n = 3) HSG examinations. In 33/142 (23%) HSG examinations, one or both
      tubes showed functional occlusion (FO). The median E2 in studies with BTP (49
      pg/mL) was significantly higher than in those studies with FO (32 pg/mL, P =
      .005). Among 18 animals with repeat examinations where serum E2 changed from <60
      to >= 60 pg/mL, 13 results changed from FO to BTP (P = .0001). No sets showed a
      change from BTP to FO with an increase in estradiol. CONCLUSION: In baboons,
      functional occlusion of the fallopian tube is associated with low estradiol
      levels, supporting a role for estrogen-mediated relaxation of the utero-tubal
      junction.

PMID- 29063624
TI  - The intestinal nematode inhibits T-cell reactivity by targeting P-GP activity.
AB  - Host immunosuppression occurs during chronic nematode infection, partly due to
      effector T-cell hyporesponsiveness. The role of P-glycoprotein (P-gp), a member
      of the ABC transporter family, has been assessed in T-cell activity. This study
      assesses the possible role of P-gp in T-cell activity during nematode infection.
      Our findings indicate that blockade of P-gp in vivo increased protection against
      Heligmosomoides polygyrus nematode infection and was associated with the enhanced
      T-cell activity. Three P-gp-inhibitors, verapamil (VRP), cyclosporine (CsA) and
      tariquidar (XR9576), were used to determine the influence of nematode infection
      on the P-gp function of T cells. The influence of the nematode on the uptake,
      efflux and kinetics of extrusion in T-cell subsets CD4+ and CD8+ was assessed by
      the accumulation of Rho123 dye. The results indicate that H. polygyrus infection
      contributes to the inhibition of T-cell function by elevating P-gp activity. The
      blockade of P-gp in the T cells of infected mice led to an impressive increase in
      T-cell proliferation and IL-4 cytokine release through the upregulation of NF
      kappaB activation. These results provide the first evidence that the P-gp
      function of T cells is altered during nematode infection to open the way for
      further studies aiming to explore the role of P-gp in host-parasite interactions.

PMID- 29063625
TI  - Effect of phenolic compounds on the growth of selected probiotic and pathogenic
      bacteria.
AB  - : Fruit extracts from different tissues (pulp, seed and peel) have shown
      antimicrobial and prebiotic activities related to their phenolic profile,
      although structure-specific evaluations have not been reported yet. The effect of
      five phenolic compounds (catechin and gallic, vanillic, ferulic and
      protocatechuic acids) identified in different fruits, particularly in mango, was
      evaluated on the growth of two probiotic (Lactobacillus rhamnosusGG ATCC 53103
      and Lactobacillus acidophilusNRRLB 4495) and two pathogenic (Escherichia coli
      0157:H7 ATCC 43890 and Salmonella enterica serovar Typhimurium ATCC 14028)
      bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) of phenolic acids ranged from 15-20 mmol l-1 and 20-30 mmol l
      1 against E. coli and S. Typhimurium, respectively. For catechin, the MIC and MBC
      were 35 mmol l-1 and >35 mmol l-1 against E. coli and S. Typhimurium,
      respectively. The presence of catechin and gallic, protocatechuic and vanillic
      acids in MRS broth without dextrose allowed the growth of lactobacilli. Catechin
      combined with protocatechuic or vanillic acid mildly allowed the growth of both
      probiotics. In conclusion, phenolic compounds can selectively inhibit the growth
      of pathogenic bacteria without affecting the viability of probiotics.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides relevant information
      about the effects of phenolic compounds commonly present in fruit and vegetables
      on the growth of probiotic and pathogenic bacteria. The compounds selectively
      allowed the growth of probiotic lactobacilli (Lactobacillus rhamnosus GG and
      Lactobacillus acidophilus) and inhibited pathogenic bacteria (Escherichia coli
      and Salmonella Typhimurium) at the same concentration (20 mmol l-1 ). These
      findings can contribute to the formulation of nutraceutical products, such as
      synbiotics, that can restore or maintain an optimal composition of human
      microbiota, potentially improving the overall health of the consumer.

PMID- 29063626
TI  - Polydopamine deposition with anodic oxidation for better connective tissue
      attachment to transmucosal implants.
AB  - BACKGROUND AND OBJECTIVE: Nowadays, most designs for the transmucosal surface of
      implants are machined-smooth. However, connective tissue adhered to the smooth
      surface of an implant has poor mechanical resistance, which can render separation
      of tissue from the implant interface and induce epithelial downgrowth.
      Modification of the transmucosal surface of implants, which can help form a good
      seal of connective tissue, is therefore desired. We hypothesized that anodic
      oxidation (AO) and polydopamine (PD) deposition could be used to enhance the
      attachment between an implant and peri-implant connective tissue. We tested this
      hypothesis in the mandibles of Beagle dogs. MATERIAL AND METHODS: AO and PD were
      used to modify the transmucosal region of transmucosal implants (implant neck).
      The surface microstructure, surface roughness and elemental composition were
      investigated in vitro. L929 mouse fibroblasts were cultured to test the effect of
      PD on cell adhesion. Six Beagle dogs were used for the in vivo experiment (n = 6
      dogs per group). Three months after building the edentulous animal model, four
      groups of implants (control, AO, PD and AO + PD) were inserted. After 4 months of
      healing, samples were harvested for histometric analyses. RESULTS: The surfaces
      of anodized implant necks were overlaid with densely distributed pores, 2-7 MUm
      in size. On the PD-modified surfaces, N1s, the chemical bond of nitrogen in PD,
      was detected using X-ray photoelectron spectroscopy. L929 developed pseudopods
      more quickly on the PD-modified surfaces than on the surfaces of the control
      group. The in vivo experiment showed a longer connective tissue seal and a more
      coronally located peri-implant soft-tissue attachment in the AO + PD group than
      in the control group (P < .05). CONCLUSION: The modification of AO + PD on the
      implant neck yielded better attachment between the implant and peri-implant
      connective tissue.

PMID- 29063628
TI  - First case of brain protection in out-of-hospital cardiac arrest.

PMID- 29063627
TI  - Impulsive Personality Traits Mediate the Relationship Between Adult Attention
      Deficit/Hyperactivity Symptoms and Alcohol Dependence Severity.
AB  - BACKGROUND: While the role of attention-deficit/hyperactivity disorder (ADHD) as
      a risk factor for developing alcohol use disorder (AUD) has been established, the
      underlying pathways connecting the two are still not fully understood.
      Overlapping constructs such as impulsivity may explain the increased risk for
      developing AUD in individuals with ADHD. METHODS: In this study, we assessed
      whether adult ADHD symptoms increase the odds of having a diagnosis of AUD.
      Furthermore, we tested whether facets of impulsivity explained the relationship
      between ADHD symptoms and alcohol dependence (AD) severity. RESULTS: In a
      logistic regression of 749 participants (464 = AD, 285 = controls), overall adult
      ADHD symptoms, and more specifically, symptoms of hyperactivity/restlessness and
      problems with self-concept, increased the odds of having a diagnosis of AD.
      Within the AD sample, we found that impulsivity mediated the relationship between
      adult ADHD symptoms and AD severity. In particular, negative and positive urgency
      meditated the relationship of overall adult ADHD symptoms, and symptoms of
      hyperactivity/restlessness and problems with self-concept with AD severity.
      CONCLUSIONS: These results highlight the importance of looking at cohorts of ADHD
      symptoms and facets of impulsivity to assess the risk of developing AUD. They
      also suggest potential avenues for intervention strategies in individuals with
      preexisting adult ADHD symptoms who are seeking treatment for AUD.

PMID- 29063629
TI  - Central carbon metabolism influences cellulase production in Bacillus
      licheniformis.
AB  - : Bacillus licheniformis that can produce cellulase including endo glucanase and
      glucosidase is an important industrial microbe for cellulose degradation. The
      purpose of this research was to assess the effect of endo glucanase gene bglC and
      glucosidase gene bglH on the central metabolic flux in B. licheniformis. bglC and
      bglH were knocked out using homologous recombination method, respectively, and
      the corresponding knockout strains were obtained for 13 C metabolic flux
      analysis. A significant change was observed in metabolic fluxes after 13 C
      metabolic flux ratio analysis. In both of the knockout strains, the increased
      fluxes of the pentose phosphate pathway and malic enzyme reaction enabled an
      elevated supply of NADPH which provided enough reducing power for the in vivo
      synthesis reactions. The fluxes through tricarboxylic acid cycle and anaplerotic
      reactions increased fast in the two knockout strains, which meant more energy
      generated. The changed fluxes in central carbon metabolism provided a holistic
      view of the physiological status in B. licheniformis and possible targets for
      further strain engineering. SIGNIFICANCE AND IMPACT OF THE STUDY: Cellulase is
      very important in the field of agriculture and bioenergy because of its degrading
      effect on cellulosic biomass. This study presented the effect of central carbon
      metabolism on cellulase production in Bacillus licheniformis. The study also
      provided a holistic view of the physiological status in B. licheniformis. The
      shifted metabolism provided a quantitative evaluation of the biosynthesis of
      cellulase and a priority ranked target list for further strain engineering.

PMID- 29063630
TI  - Isolation and characterization of multidrug-resistant Leclercia species from
      animal clinical case.
AB  - : Leclercia adecarboxylata, a Gram-negative bacillus of family
      Enterobacteriaceae, is an uncommonly identified pathogen isolated from
      environmental and clinical specimens. Most of the human infections are
      polymicrobial and commonly occur in immunocompromised hosts, although nosocomial
      infections in immunocompetent hosts have been documented. Here, we describe the
      case of isolation of Leclercia species as polymicrobial infection from bovine
      suffering from respiratory distress in Chhattisgarh state of India. The isolates
      were identified by their phenotypes, 16S rDNA sequencing and MALDI-TOF-MS. The
      isolate was found to be resistant to aminoglycosides and fluoroquinolone
      antibiotics and intermediate resistant to cephalosporins and evidenced for
      uncertain clinical relevance and could act as hidden source of public health
      hazard. SIGNIFICANCE AND IMPACT OF THE STUDY: Leclercia adecarboxylata is a
      rarely reported human pathogen. We report here the case from bovine suffering
      from respiratory distress; the sample yielded Leclercia species as polymicrobial
      culture. The isolate was found to be multidrug resistant and evidenced for
      uncertain clinical relevance and could act as hidden source of public health
      hazard. The limited literature available on this organism is reviewed, and the
      potential implications of findings are discussed. To the best of our knowledge,
      this is the first report of isolation and characterization of multidrug-resistant
      Leclercia species from animal clinical case from India.

PMID- 29063632
TI  - Highway driving safety the day after using sleep medication: the direction of
      lapses and excursions out-of-lane in drowsy drivers.
AB  - The primary outcome measure of the on-road driving test is the Standard Deviation
      of Lateral Position. However, other outcome measures, such as lapses and
      excursions out-of-lane, also need to be considered as they may be related to
      crash risk. The aim of this study was to determine the direction of lapses and
      excursions out-of-lane (i.e. towards/into the adjacent traffic lane or
      towards/into the road shoulder). In total, data from 240 driving tests were re
      analysed, and 628 lapses and 401 excursions out-of-lane were identified. The
      analyses revealed that lapses were made equally frequently over left (49.4%) and
      over right (43.3%). In contrast, excursions out-of-lane were almost exclusively
      directed over right into the (safer) road shoulder (97.3%). These findings
      suggest that drivers are unaware of having lapses, whereas excursions out-of-lane
      are events where the driver is aware of loss of vehicle control.

PMID- 29063631
TI  - Donor-specific individuality of red blood cell performance during storage is
      partly a function of serum uric acid levels.
AB  - BACKGROUND: Previous investigations in leukoreduced units of red blood cells
      (RBCs) in mannitol additive solution revealed the close association of uric acid
      (UA) levels in vivo with the susceptibility of RBCs to storage lesion markers. In
      this study, we examined whether UA has a similar correlation with the capability
      of RBCs to cope with the oxidative provocations of storage under different
      conditions, namely, in CPDA-1 and in the absence of leukoreduction. STUDY DESIGN
      AND METHODS: The UA-dependent antioxidant capacity of the supernatant was
      measured in nonleukoreduced units of RBCs in CPDA (n = 47). The possible effect
      of UA variability on the storage lesion profile was assessed by monitoring
      several physiologic properties of RBCs and supernatant, including cell shape,
      reactive oxygen species, and size distribution of extracellular vesicles, in
      units exhibiting the lowest or highest levels of UA activity (n = 16) among
      donors, throughout the storage period. RESULTS: In stored RBC units, the UA
      dependent antioxidant activity of the supernatant declined as a function of
      storage duration but always in strong relation to the UA levels in fresh blood.
      Contrary to units of poor-UA activity, RBCs with the highest levels of UA
      activity exhibited better profile of calcium- and oxidative stress-driven
      modifications, including a significant decrease in the percentages of spherocytes
      and of 100- to 300-nm-sized vesicles, typically associated with the
      exovesiculation of stored RBCs. CONCLUSION: The antioxidant activity of UA is
      associated with donor-specific differences in the performance of RBCs under
      storage in nonleukoreduced CPDA units.

PMID- 29063633
TI  - In search of a common currency: A comparison of seven EQ-5D-5L value sets.
AB  - The recently published EQ-5D-5L value sets from Canada, England, Japan, Korea,
      the Netherlands, Spain, and Uruguay are compared with an aim to identify any
      similarities in preference pattern. We identify some striking similarities for
      Canada, England, the Netherlands, and Spain in terms of (a) the relative
      importance of the 5 dimensions; (b) the relative utility decrements across the 5
      levels; and (c) the scale length. On the basis of the observed similarities
      across these 4 Western countries, we develop an amalgam model, WePP (western
      preference pattern), and compare it with these 4 value sets. The values generated
      by this model show a high degree of concordance with those of England, Canada,
      and Spain. Patient level data were obtained from the Multi-Instrument Comparison
      project, which includes participants from 6 countries in 7 disease groups (N =
      7,933): The WePP values lie within the confidence intervals for the value sets in
      Canada, England, and Spain across the whole severity distribution. We suggest
      that the WePP model represents a useful "common currency" for (Western) countries
      that have not yet developed their own value sets. Further research is needed to
      disentangle the differences between value sets due to preference heterogeneity
      from those stemming from methodological differences.

PMID- 29063634
TI  - Health-care quality and information failure: Evidence from Nigeria.
AB  - Low-quality health services are a problem across low- and middle-income
      countries. Information failure may contribute, as patients may have insufficient
      knowledge to discern the quality of health services. That decreases the
      likelihood that patients will sort into higher quality facilities, increasing
      demand for better health services. This paper presents results from a health
      survey in Nigeria to investigate whether patients can evaluate health service
      quality effectively. Specifically, this paper demonstrates that although more
      than 90% of patients agree with any positive statement about the quality of their
      local health services, satisfaction is significantly associated with the
      diagnostic ability of health workers at the facility. Satisfaction is not
      associated with more superficial characteristics such as infrastructure quality
      or prescriptions of medicines. This suggests that patients may have sufficient
      information to discern some of the most important elements of quality, but that
      alternative measures are crucial for gauging the overall quality of care.

PMID- 29063635
TI  - Immunogenicity of a Glycoconjugate from Hydrazine-Detoxified Lipopolysaccharide
      of Vibrio cholerae O139.
AB  - A glycoconjugate (dLPS-CBSA) from hydrazine-detoxified lipopolysaccharide (LPS)
      of Vibrio cholerae O139 and BSA was used for immunization of BALB/c mice. The
      immunogenicity (concentration of induced IgG antibodies) of the conjugate was
      determined by enzyme-linked immunosorbent assay. The highest level of LPS
      specific IgGs was found in sera collected 2 weeks after the third immunization.
      Both IgM and IgG antibodies present in the anti-V. cholerae O139-specific sera
      showed long-lasting vibriocidal activity. The glycoconjugate also stimulated
      production of IL-4, IL-6, IFNgamma, TNFalpha and IL-10. Immunization with the
      conjugate induced significant production of both Th1 and Th2 cytokine sets,
      indicating balanced Th1/Th2 immune response polarization. The quantitative
      analysis of total and LPS-specific IgM and IgG antibodies production by B
      lymphocytes (from both the spleen and the bone marrow) was performed by ELISPOT
      assay. From the analysis of antibodies produced directly by B lymphocytes in the
      bone marrow (of dLPS-CBSA immunized mice), we were able to identify the IgM-IgG
      switch in the antibodies produced.

PMID- 29063636
TI  - Presence of cancer cells in gastric lavage of gastric cancer patients as an
      indicator of advanced disease, predictor of tumour aggressive phenotype and
      independent prognostic factor for poor survival: The endoluminal metastatic
      pathway of gastric cancer and GL0/GL1 classification.
AB  - OBJECTIVE: As of 2017, the pathobiology of gastric cancer (GC) is far from fully
      understood; consequently, new methods of basic and advanced research have been
      proposed and tested. The presence (GL1) vs absence (GL0) of malignant cells
      exfoliated in gastric lavage (GL) of GC patients was formerly evaluated with
      diagnostic intent but not for staging or prognostic assessment. We investigated
      this hitherto unreported application of cytopathology. METHODS: GL was
      preoperatively and prospectively collected from 80 GC patients and cytologically
      analysed. The results were compared with the classic clinicopathological features
      of GC and related to survival. The prognostic value of GL1 was assessed through
      univariate and multivariate analyses. RESULTS: GL1 was detected in 36 samples
      (45%) and correlated with advanced tumour depth (T3-T4), lymphatic metastasis
      (N+), distant metastasis (M1) and lymphovascular invasion (LVI1; P=.0317, .0024,
      .003 and .0028, respectively). Overall survival (OS) was significantly shorter
      for GL1 (23 months) vs GL0 patients (42 months; P=.005) and GL1 vs GL0 T1
      subjects (12.6 vs 47.8 months, P=.0029). Univariate analysis revealed that GL1,
      N+, M1, LVI1 and advanced stage were significantly associated with OS.
      Multivariate analysis assessed GL1 as the only independent prognostic factor for
      worse OS and progression-free survival (P=.0013 and .0107). CONCLUSIONS: In the
      present study, GL1 was correlated with advanced disease, aggressive tumour
      behaviour and poor prognosis. Although additional studies are needed to confirm
      these findings, the GL0/GL1 classification can be applied to GC patients to
      achieve higher accuracy in staging, prognostic stratification and treatment
      selection.

PMID- 29063637
TI  - Phenotypic Prenatal Diagnosis of Chronic Granulomatous Disease: A Useful Tool in
      The Absence Of Molecular Diagnosis.
AB  - Chronic granulomatous disease (CGD) is an inherited immunodeficiency disorder
      affecting the microbicidal function of the phagocytes. It is characterized by
      susceptibility to recurrent infections leading to significant morbidity and
      mortality. Antibacterial and antifungal prophylaxis, though, has significantly
      reduced the rate and severity of the infections; the breakthrough infections
      still remain a challenge. Currently, allogenic haematopoietic stem cell
      transplantation is the only curative option which is very expensive and
      unavailable for many due to lack of suitable donor. Thus, prenatal diagnosis
      (PND) forms an important component of management in the affected families. PND is
      challenging in families approaching late in pregnancy with an uncharacterized
      molecular defect. In such cases, PND can be performed by analysis of NADPH
      activity of fetal blood (FB) neutrophils at 18-20 weeks of gestation. Cord blood
      samples at 18 weeks of gestation from healthy control were used to establish
      normal ranges for NBT and DHR. PND was offered for six pregnancies (NBT: n = 3,
      DHR: n = 6) with index cases of CGD confirmed by abnormal NBT and DHR analysis.
      NBT and DHR tests were found to be negative for all the six cases, confirming the
      same on samples post-delivery. NBT and DHR tests offer a rapid and sensitive PND
      of CGD in the absence of facilities for molecular diagnosis. It was observed that
      addition of CD15 along with CD45 led to an accurate DHR analysis. It is
      recommended to perform the diagnosis with adequate precautions only at centres
      with considerable experience and expertise in the diagnosis of CGD.

PMID- 29063638
TI  - Repeated ultraviolet irradiation induces the expression of Toll-like receptor 4,
      IL-6, and IL-10 in neonatal human melanocytes.
AB  - BACKGROUND: Human melanocytes express Toll-like receptor 4 (TLR4), which
      regulates ultraviolet (UV)-induced cutaneous immunosuppression in Langerhans
      cells. Lipopolysaccharide (LPS) stimulation increases melanocyte pigmentation and
      TLR4 expression, while inducing local innate inflammatory responses. AIMS: We
      investigated whether UV radiation induces TLR4 expression in neonatal human
      melanocytes (NHMs) and how this affects the immune system. METHODS: We cultured
      NHMs with LPS treatment or with one-time or repeated UVA or UVB exposure, and
      investigated and compared the effects on TLR4 expression, melanin contents, and
      cytokine production. RESULTS: NHMs in the resting state did not express TLR4. LPS
      stimulation induced TLR4 expression and increased pigmentation. TLR4 expression
      was not detected after single-dose UVA or UVB treatment, but pigmentation
      increased. Repeated UV treatment induced TLR4 expression and increased
      pigmentation. LPS stimulation and repeated UV treatment increased IL-6 secretion,
      and repeated UVB treatment increased IL-10 secretion. CONCLUSION: These results
      suggest that human melanocytes may actively participate in UV-induced immune
      modulation.

PMID- 29063639
TI  - Calibrating actigraphy to improve sleep efficiency estimates.
AB  - Actigraphy (ACT) can enhance treatment for insomnia by providing objective
      estimates of sleep efficiency; however, only two studies have assessed the
      accuracy of actigraphy-based estimates of sleep efficiency (ACT-SE) in sleep
      disordered samples studied at home. Both found poor correspondence with
      polysomnography-based estimates (PSG-SE). The current study tested that
      concordance in a third sample and piloted a method for improving ACT-SE.
      Participants in one of four diagnostic categories (panic disorder, post-traumatic
      stress disorder, comorbid post-traumatic stress and panic disorder and controls
      without sleep complaints) underwent in-home recording of sleep using concurrent
      ambulatory PSG and actigraphy. Precisely synchronized PSG and ACT recordings were
      obtained from 41 participants. Sleep efficiency was scored independently using
      conventional methods, and ACT-SE/PSG-SE concordance examined. Next, ACT data
      recorded initially at 0.5 Hz were resampled to 30-s epochs and rescaled on a per
      participant basis to yield optimized concordance between PSG- and ACT-based sleep
      efficiency estimates. Using standard scoring of ACT, the correlation between ACT
      SE and PSG-SE across participants was statistically significant (r = 0.35, P <
      0.025), although ACT-SE failed to replicate a main effect of diagnosis.
      Individualized calibration of ACT against a night of PSG yielded a significantly
      higher correlation between ACT-SE and PSG-SE (r = 0.65, P < 0.001; z = 1.692, P =
      0.0452, one-tailed) and a significant main effect of diagnosis that was highly
      correspondent with the effect on PSG-SE. ACT-based estimates of sleep efficiency
      in sleep-disordered patients tested at home can be improved significantly by
      calibration against a single night of concurrent PSG.

PMID- 29063640
TI  - Amyotrophic lateral sclerosis and parkinsonism-dementia complex of the Hohara
      focus of the Kii Peninsula: A multiple proteinopathy?
AB  - The high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism
      dementia complex (PDC) has been previously known in the Kii Peninsula of Japan
      and in Guam. Recently, the accumulation of various proteins, such as tau, trans
      activation response DNA binding protein 43 kDa (TDP-43), and alpha-synuclein
      (alphaSyn), was reported in the brains of patients with ALS/PDC in Guam. To
      confirm whether similar findings are present in Kii ALS/PDC, we
      neuropathologically examined the brains and spinal cords of 18 patients with
      ALS/PDC (clinical diagnoses: eight ALS and 10 PDC) in Hohara Village, which is
      the eastern focus of Kii ALS. The average age at death was 71.6 years, and 16
      patients (88.9%) had a family history of ALS/PDC. Autopsy specimens were
      immunohistochemically examined with antibodies against four major proteins.
      Neurofibrillary tangles, including ghost tangles, and tau-positive astrocytes
      were distributed widely in all of the brains examined, and TDP-43-positive
      neuronal cytoplasmic inclusions were observed mainly in the limbic system.
      Synuclein pathology was present in 14 patients (77.8%). These patients were
      classified into three pathological subtypes according to the most prominent
      proteinopathy: the tauopathy-dominant type, the TDP-43 proteinopathy-dominant
      type, and the synucleinopathy-dominant type. Five patients with severe tau
      deposition showed clinical features of atypical parkinsonism and dementia with or
      without motor neuron disease. Eight patients were predominated by phosphorylated
      TDP-43 inclusions and clinically showed ALS, and five patients were predominated
      by synuclein pathology and clinically showed signs of PDC. Based on the common
      characteristic tau pathology, three subtypes seemed to be pathologically
      continuous on a spectrum of a single disease. Thus, we conclude that ALS/PDC in
      the Hohara focus of the Kii Peninsula is a single disease characterized
      neuropathologically by a multiple proteinopathy, even though the clinical
      manifestations of the three subtypes differed from each other. It remains unclear
      whether the coexistence of the three proteinopathies was incidental or
      pathogenetically related.

PMID- 29063641
TI  - Fluorine-19 magnetic resonance imaging probe for the detection of tau pathology
      in female rTg4510 mice.
AB  - Aggregation of tau into neurofibrillary tangles (NFTs) is characteristic of
      tauopathies, including Alzheimer's disease. Recent advances in tau imaging have
      attracted much attention because of its potential contributions to early
      diagnosis and monitoring of disease progress. Fluorine-19 magnetic resonance
      imaging (19 F-MRI) may be extremely useful for tau imaging once a high-quality
      probe has been formulated. In this investigation, a novel fluorine-19-labeling
      compound has been developed as a probe for tau imaging using 19 F-MRI. This
      compound is a buta-1,3-diene derivative with a polyethylene glycol side chain
      bearing a CF3 group and is known as Shiga-X35. Female rTg4510 mice (a mouse model
      of tauopathy) and wild-type mice were intravenously injected with Shiga-X35, and
      magnetic resonance imaging of each mouse's head was conducted in a 7.0-T
      horizontal-bore magnetic resonance scanner. The 19 F-MRI in rTg4510 mice showed
      an intense signal in the forebrain region. Analysis of the signal intensity in
      the forebrain region revealed a significant accumulation of fluorine-19 magnetic
      resonance signal in the rTg4510 mice compared with the wild-type mice.
      Histological analysis showed fluorescent signals of Shiga-X35 binding to the NFTs
      in the brain sections of rTg4510 mice. Data collected as part of this
      investigation indicate that 19 F-MRI using Shiga-X35 could be a promising tool to
      evaluate tau pathology in the brain.

PMID- 29063642
TI  - Neonatal maternal separation opposes the facilitatory effect of castration on the
      respiratory response to hypercapnia of the adult male rat: Evidence for the
      involvement of the medial amygdala.
AB  - Respiratory manifestations of panic disorder (PD) include a greater respiratory
      instability and enhanced responsiveness to CO2 compared to normal individuals.
      Although the prevalence of PD is approximately three times greater in women
      compared to men, the origins of this sexual dimorphism remain poorly understood.
      Similar to PD patients, adult female rats previously subjected to neonatal
      maternal separation (NMS) show an increase in their ventilatory response to CO2 .
      Because this effect of NMS is not observed in males, we hypothesised that
      testosterone prevents NMS-induced hyper-responsiveness to CO2 . Pups subjected to
      NMS were placed in an incubator for 3 h d-1 from postnatal days 3-12. Control
      pups remained undisturbed. At adulthood (8-10 weeks of age), rats were then
      subjected either to sham surgery or castration. Fourteen days later, breathing
      was measured at rest (room air) and during acute exposure to hypercapnia (5 and
      10% CO2 for 10 minutes each) using plethysmography. To gain insight into the
      mechanisms involved, c-fos expression was used as an indicator of neuronal
      activation. Brains were collected following air or CO2 exposure for
      quantification of c-fos positive cells by immunohistochemistry in selected
      regions, including the paraventricular nucleus of the hypothalamus, the
      dorsomedial hypothalamus and the amygdalar complex. Castration produced a 100%
      increase of hyperventilatory response to 10% CO2 in control rats. Unexpectedly,
      castration had no effect on the hyperventilatory response of NMS rats. The
      intensity of the hypercapnic response was inversely correlated with c-fos
      expression in the medial amygdala. We conclude that testosterone prevents the
      hyper-responsiveness to CO2 , whereas NMS attenuates sensitivity to hormone
      withdrawal. We propose that an inhibitory influence from the medial amygdala
      contributes to this effect.

PMID- 29063643
TI  - Primary central nervous system extranodal nasal-type natural killer/T-cell
      lymphoma with CD20 expression.
AB  - We report a unique case of primary CNS extranodal natural killer/T-cell lymphoma
      (PCNS ENKTCL) with CD20 expression and the monoclonal rearrangement of Ig heavey
      chain (IgH) gene. Resection specimens were evaluated using HE-stained sections,
      immunohistochemistry, in situ hybridization and PCR. Histopathologic examination,
      immunohistochemistry and molecular studies showed the intermediate-sized lymphoma
      cells expressing CD2, CD3epsilon, granzyme B, TIA-1, CD20 and Epstein-Barr virus
      encoded RNA, with germline T-cell receptor gene and the monoclonal rearrangement
      of IgH gene. Clinicopathologic and radiographic evaluation indicated the lesion
      was of exclusive left cerebellar localization. Thus, PCNS ENKTCL with the CD20
      expression was diagnosed. ENKTCL with both CD20-positive expression and the
      monoclonal rearrangement of IgH gene may be mistaken for B-cell lymphoma; thus,
      the comprehensive evaluation of histomorphology, more extensive immunoprofiles
      and molecular studies is essential to reach the correct diagnosis. The rare PCNS
      ENKTCL shows a highly aggressive nature and a poorer prognosis.

PMID- 29063644
TI  - Chylous leakage after axillary lymph node dissection in a patient with breast
      cancer.

PMID- 29063645
TI  - Curriculum content in geriatric dentistry in USA dental schools.
AB  - OBJECTIVES: The aim of this study was to re-examine the teaching of geriatric
      dentistry in the USA dental schools, to identify curriculum content and compare
      the findings to previous reports. METHODS: All dental schools in the United
      States were contacted via email with a questionnaire to assess the teaching of
      geriatric dentistry. Non-responding schools were sent a minimum of three reminder
      emails to complete the survey. A statistical analysis was performed. Descriptive
      statistics were conducted to profile the variables of interest. Bivariate
      analysis was performed to explore if any of the variables were related using
      Fisher's exact test, non-parametric Wilcoxon rank-sum test and the Kruskal-Wallis
      test. RESULTS: Fifty-six of the 67 dental schools completed the questionnaire.
      Geriatric dentistry was taught in all dental schools; for 92.8%, the course was
      compulsory. We found that 62.5% were teaching it as an independent course, 25% as
      an organised series of lectures and 8.9% as occasional lectures in parts of other
      courses. Clinically, 84.2% have some form of compulsory education in geriatric
      dentistry. Public schools were marginally associated with an increased interest
      in expanding the geriatric dentistry curriculum (P = .078). No differences were
      found between these variables and school location. CONCLUSIONS: Geriatric
      dentistry is now required in 92.8% of dental schools. The teaching of traditional
      topics has not changed much; however, the number of gerontological topics has
      increased. Clinical teaching needs to be expanded, as in only 57.1% of schools
      was it a requirement. The ageing imperative will require research to determine
      the impact of teaching on services to the geriatric community.

PMID- 29063646
TI  - Direct Aryl C-H Amination with Primary Amines Using Organic Photoredox Catalysis.
AB  - The direct catalytic C-H amination of arenes is a powerful synthetic strategy
      with useful applications in pharmaceuticals, agrochemicals, and materials
      chemistry. Despite the advances in catalytic C-H functionalization, the use of
      aliphatic amine coupling partners is limited. Described herein is the
      construction of C-N bonds, using primary amines, by direct C-H functionalization
      with an acridinium photoredox catalyst under an aerobic atmosphere. A wide
      variety of primary amines, including amino acids and more complex amines are
      competent coupling partners. Various electron-rich aromatics and heteroaromatics
      are useful scaffolds in this reaction, as are complex, biologically active
      arenes. We also describe the ability to functionalize arenes that are not
      oxidized by an acridinium catalyst, such as benzene and toluene, thus supporting
      a reactive amine cation radical intermediate.

PMID- 29063647
TI  - Fast Heavy-Atom Tunneling in Trifluoroacetyl Nitrene.
AB  - Chemical reactions involving quantum mechanical tunneling (QMT) increasingly
      attract the attention of scientists. In contrast to the hydrogen-tunneling as
      frequently observed in chemistry and biology, tunneling solely by heavy atoms is
      rare. Herein, we report heavy-atom tunneling in trifluoroacetyl nitrene, CF3
      C(O)N. The carbonyl nitrene CF3 C(O)N in the triplet ground state was generated
      in cryogenic matrices by laser (193 or 266 nm) photolysis of CF3 C(O)N3 and
      characterized by IR and EPR spectroscopy. In contrast to the theoretically
      predicted activation barriers (>10 kcal mol-1 ), CF3 C(O)N undergoes rapid
      rearrangement into CF3 NCO with half-life times of less than 10 min and
      unprecedentedly large 14 N/15 N kinetic isotope effects (1.18-1.33) in solid Ar,
      Ne, and N2 matrices even at 2.8 K. The tunneling disappearance of CF3 C(O)N
      becomes much slower in the chemically active toluene and in 2
      methyltetrahydrofuran at 5 K.

PMID- 29063648
TI  - Conditional relative survival among female breast cancer patients in the United
      States.

PMID- 29063649
TI  - Atomically Dispersed Copper-Platinum Dual Sites Alloyed with Palladium Nanorings
      Catalyze the Hydrogen Evolution Reaction.
AB  - Designing highly active catalysts at an atomic scale is required to drive the
      hydrogen evolution reaction (HER). Copper-platinum (Cu-Pt) dual sites were
      alloyed with palladium nanorings (Pd NRs) containing 1.5 atom % Pt, using
      atomically dispersed Cu on ultrathin Pd NRs as seeds. The ultrafine structure of
      atomically dispersed Cu-Pt dual sites was confirmed with X-ray absorption fine
      structure (XAFS) measurements. The Pd/Cu-Pt NRs exhibit excellent HER properties
      in acidic solution with an overpotential of only 22.8 mV at a current density of
      10 mA cm-2 and a high mass current density of 3002 A g-1(Pd+Pt) at a -0.05 V
      potential.

PMID- 29063650
TI  - Access to Chiral Hydropyrimidines through Palladium-Catalyzed Asymmetric Allylic
      C-H Amination.
AB  - A palladium-catalyzed asymmetric intramolecular allylic C-H amination controlled
      by a chiral phosphoramidite ligand was established for the preparation of various
      substituted chiral hydropyrimidinones, the precursors of hydropyrimidines, in
      high yields with high enantioselectivities. In particular, dienyl sodium N
      sulfonyl amides bearing an arylethene-1-sulfonyl group underwent a sequential
      allylic C-H amination and intramolecular Diels-Alder (IMDA) reaction to produce
      chiral fused tricyclic tetrahydropyrimidinone frameworks in high yields and with
      high levels of stereoselectivity. Significantly, this method was used as the key
      step in an asymmetric synthesis of letermovir.

PMID- 29063651
TI  - Area under the curve of temporal estrogen and progesterone measurements during
      assisted reproductive technology: Which hormone is the main determinant of cycle
      outcome?
AB  - AIM: Is there any relationship between estrogen and progesterone concentrations
      during assisted reproductive technology (ART)? Which hormone is the main
      determinant of impaired endometrial receptivity? METHODS: This study was
      conducted from July to December 2016 at the in vitro
      Fertilization/Intracytoplasmic Sperm Injection unit at Zeynep Kamil Women and
      Children's Health Training and Research Hospital. A total of 289 women who
      underwent ART were prospectively screened and areas under the curve of temporal
      estrogen (AUCEM) and progesterone measurements (AUCPM) were calculated for each
      participant. Women were included if they had regular menstrual cycles, normal
      serum prolactin levels and had not received hormone treatment within three
      months. ART was indicated in all patients for unexplained infertility. Patients
      were divided into two groups: with (n = 90) and without (n = 199) embryo
      implantation. The relationship between the two AUCs and ART success was assessed
      in terms of embryo implantation and clinical pregnancy. RESULTS: Implantation was
      successful in 90 (31.1%) women, and a fetal heart rate was detected in 83 (28.7%)
      cases. There was a significant correlation between AUCEM and AUCPM (r = 0.525, P
      < 0.001). Multivariate regression analysis showed significant associations
      between failure of implantation, lack of clinical pregnancy and AUCEM (beta
      coefficient = 0.311, P < 0.001; beta coefficient = 0.297, P < 0.001,
      respectively) after adjusting for AUCPM. CONCLUSION: Our data showed that the
      degree of endometrial estrogen exposure is the main factor functioning as a
      detrimental effect of ovarian stimulation on endometrial receptivity.

PMID- 29063652
TI  - Evaluation of prophylactic therapy in haemophilia with global coagulation tests.

PMID- 29063653
TI  - Unraveling the Mechanism for the Sharp-Tip Enhanced Electrocatalytic Carbon
      Dioxide Reduction: The Kinetics Decide.
AB  - The electrocatalytic reduction reaction of carbon dioxide can be significantly
      enhanced by the use of a sharp-tip electrode. However, the experimentally
      observed rate enhancement is many orders of magnitudes smaller than what would be
      expected from an energetic point of view. The kinetics of this tip-enhanced
      reaction are shown to play a decisive role, and a novel reaction-diffusion
      kinetic model is proposed. The experimentally observed sharp-tip enhanced
      reaction and the maximal producing rate of carbon monoxide under different
      electrode potentials are well-reproduced. Moreover, the optimal performance shows
      a strong dependence on the interaction between CO2 and the local electric field,
      on the adsorption rate of CO2 , but not on the reaction barrier. Two new
      strategies to further enhance the reaction rate have also been proposed. The
      findings highlight the importance of kinetics in modeling electrocatalytic
      reactions.

PMID- 29063655
TI  - Ultrasound-guided wire localization of focal ductal dilatation in the evaluation
      and treatment of pathologic nipple discharge.
AB  - Patients presenting with pathologic nipple discharge (PND) often pose a
      diagnostic and therapeutic challenge. We used ultrasound to identify focal ductal
      dilatation-hypothesized to be a radiographic manifestation of the causative
      lesion-in patients with PND and no relevant clinical or radiographic findings.
      Twenty-two excisions guided by ultrasound wire localization of focal duct
      dilation were performed. Surgical pathology revealed papilloma in 20 cases (91%);
      atypia or carcinoma was detected in 7 cases (32%). The ultrasound finding of
      focal duct dilatation enables excision of otherwise occult though clinically
      significant lesions and is worthy of further study.

PMID- 29063654
TI  - Improvements in peripheral vascular function with vitamin D treatment in
      deficient adolescents with type 1 diabetes.
AB  - BACKGROUND: Vitamin D (VitD) deficiency is prevalent in adolescents with type 1
      diabetes (T1D) and is associated with diabetes-related vascular complications in
      adulthood. The objective of this clinical trial was to assess VitD treatment on
      endothelial function (EF) and markers of renal inflammation, in this patient
      group. METHODS: Adolescents with T1D with suboptimal levels of VitD (<37.5
      nmol/L) were treated for 12 to 24 weeks with a VitD analog (VitD3 ) at doses of
      1000 or 2000 IU daily. The primary end-point assessed the change in reactive
      hyperemia index (lnRHI), a measure of EF. Secondary end-points included changes
      in blood pressure, lipid profile, HbA1c and albumin creatinine ratio (ACR).
      Urinary cytokine/chemokine inflammatory profile was also assessed in a subset of
      subjects posttreatment. RESULTS: Two hundred and seventy-one subjects were
      screened for VitD status and 31 VitD deficient subjects with a mean age of 15.7
      +/- 1.4 years were enrolled and completed the study. Mean 25-OH-VitD levels
      significantly increased (33.0 +/- 12.8 vs 67.0 +/- 23.2 nmol/L, P < .01) with a
      significant improvement in EF following VitD supplementation (lnRHI 0.58 +/- 0.20
      vs 0.68 +/- 0.21, P = .03). VitD supplementation did not significantly impact
      systolic blood pressure/diastolic blood pressure (SBP/DBP), lipids, HbA1c and ACR
      and no adverse effects were seen. Several urinary inflammatory
      cytokines/chemokines: MCP-3 (P < .01), epidermal growth factor (EGF) (P < .01)
      tumor necrosis factor beta (TNFbeta) (P = .01), interleukin-10 (IL-10) (P = .01),
      also significantly decreased post-VitD-treatment. CONCLUSIONS: Treatment with
      VitD was associated with an improvement in EF and reduced expression of urinary
      inflammatory markers in adolescents with T1D. This data is suggestive of an
      additional benefit of VitD supplementation on early markers of microvascular
      complications.

PMID- 29063656
TI  - Micropapillary variant of mucinous breast carcinoma: A distinct subtype.
AB  - Invasive micropapillary carcinoma of the breast is a subtype with high malignant
      potential characterized by lymphovascular invasion (LVI) and a predilection for
      axillary lymph node (AXLN) metastases. In contrast, pure mucinous breast
      carcinoma (MBC) is relatively indolent with low metastatic potential. Recent
      studies have described a histologic variant of breast cancer that displays
      combined mucinous and micropapillary patterns, ie, micropapillary variant of
      mucinous carcinoma (MpVMBC). This underrecognized variant is, as yet,
      incompletely characterized clinicopathologically. Extant reports suggest a more
      aggressive lesion than pure MBC with greater propensity for both LVI and AXLN
      metastases. Here we present our institution's experience with MpVMBCs including
      clinicopathologic and immunohistochemical (IHC) analyses. Greater awareness and
      recognition of this variant could positively contribute to patient care by (1)
      avoiding underestimation of malignant potential for individuals whose tumors may
      have been diagnosed as simply "MBC, not otherwise specified", and (2)
      recommending a postsurgical adjuvant approach emphasizing the hormone receptor
      targets, even perhaps in younger women presenting with AXLN positive disease.

PMID- 29063657
TI  - Cancer identified in accessory breast tissue within the mid axilla.

PMID- 29063658
TI  - Physiological augmentation of esophageal distension pressure and peristalsis
      during conditions of increased esophageal emptying resistance.
AB  - BACKGROUND: Abdominal compression has been implemented as a provocative maneuver
      in high-resolution impedance manometry (HRIM) to "challenge" normal esophageal
      physiology with the aim of revealing abnormal motor patterns which may explain
      symptoms. In this study, we measured the effects of abdominal compression on
      esophageal functioning utilizing novel pressure-impedance parameters and
      attempted to identify differences between healthy controls and globus patients.
      METHODS: Twenty-two healthy volunteers (aged 23-32 years, 41% female) and 22
      globus patients (aged 23-72 years, 68% female) were evaluated with HRIM using a
      3.2-mm water perfused manometric and impedance catheter. All participants
      received 10 * 5 mL liquid swallows; healthy controls also received 10 * 5 mL
      liquid swallows with abdominal compression created using an inflatable cuff. All
      swallows were analyzed to assess esophageal pressure topography (EPT) and
      pressure-flow metrics, indicative of distension pressure, flow timing and bolus
      clearance were derived. KEY RESULTS: The effect of abdominal compression was
      shown as a greater contractile vigor of the distal esophagus by EPT and higher
      distension pressure based on pressure-flow metrics. Age and body mass index also
      increased contractile vigor and distension pressure. Globus patients were similar
      to controls. CONCLUSIONS AND INTERFERENCES: Intrabolus pressure and contractile
      vigor are indicative of the physiological modulation of bolus transport
      mechanisms. Provocative testing by abdominal compression induces changes in these
      esophageal bolus dynamics.

PMID- 29063659
TI  - Quantitative losses vs. qualitative stability of ectomycorrhizal community
      responses to 3 years of experimental summer drought in a beech-spruce forest.
AB  - Forest ecosystems in central Europe are predicted to face an increasing frequency
      and severity of summer droughts because of global climate change. European beech
      and Norway spruce often coexist in these forests with mostly positive effects on
      their growth. However, their different below-ground responses to drought may lead
      to differences in ectomycorrhizal (ECM) fungal community composition and
      functions which we examined at the individual root and ecosystem levels. We
      installed retractable roofs over plots in Kranzberg Forest (11 degrees 39'42"E,
      48 degrees 25'12"N; 490 m a.s.l.) to impose repeated summer drought conditions
      and assigned zones within each plot where trees neighboured the same or different
      species to study mixed species effects. We found that ECM fungal community
      composition changed and the numbers of vital mycorrhizae decreased for both tree
      species over 3 drought years (2014-2016), with the ECM fungal community diversity
      of beech exhibiting a faster and of spruce a stronger decline. Mixed stands had a
      positive effect on the ECM fungal community diversity of both tree species after
      the third drought year. Ectomycorrhizae with long rhizomorphs increased in both
      species under drought, indicating long-distance water transport. However, there
      was a progressive decline in the number of vital fine roots during the
      experiment, resulting in a strong reduction in enzyme activity per unit volume of
      soil. Hydrolytic enzyme activities of the surviving ectomycorrhizae were stable
      or stimulated upon drought, but there was a large decline in ECM fungal species
      with laccase activity, indicating a decreased potential to exploit nutrients
      bound to phenolic compounds. Thus, the ectomycorrhizae responded to repeated
      drought by maintaining or increasing their functionality at the individual root
      level, but were unable to compensate for quantitative losses at the ecosystem
      level. These findings demonstrate a strong below-ground impact of recurrent
      drought events in forests.

PMID- 29063660
TI  - Localized Supramolecular Peptide Self-Assembly Directed by Enzyme-Induced Proton
      Gradients.
AB  - Electrodes are ideal substrates for surface localized self-assembly processes.
      Spatiotemporal control over such processes is generally directed through the
      release of ions generated by redox reactions occurring specifically at the
      electrode. The so-used gradients of ions proved their effectiveness over the last
      decade but are in essence limited to material-based electrodes, considerably
      reducing the scope of applications. Herein is described a strategy to
      enzymatically generate proton gradients from non-conductive surfaces. In the
      presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film
      provides a flow of protons through enzymatic oxidation of glucose by GOx. The
      confined acidic environment located at the solid-liquid interface allows the self
      assembly of Fmoc-AA-OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides
      into beta-sheet nanofibers exclusively from and near the surface. In the absence
      of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase
      (HRP) similarly induces Fmoc-AA-OH self-assembly.

PMID- 29063661
TI  - A simple screening test to recognize fibromyalgia in primary care patients with
      chronic pain.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Primary care providers are increasingly expected
      to recognize and treat fibromyalgia (FM) without significant interaction with
      rheumatologists. The purpose of this study was to evaluate the potential
      usefulness of 3 simple measures (tenderness to digital pressure, BP cuff-evoked
      pain, and a single patient question) as a screening test for possible FM in a
      patient with chronic pain. METHODS: A total of 352 patients (mean age 50 +/- 16.3
      years, 70% female) scheduled for routine examination in 2 primary care practices
      were studied. They were comprised of 52 patients (14.8%) who carried a chart
      diagnosis of FM, 108 (30.7%) with chronic pain but not FM, and 192 who had
      neither pain nor FM (54.5%). Subjects were assessed for tenderness to digital
      pressure at 10 locations, BP cuff-evoked pain, and a single question, "I have a
      persistent deep aching over most of my body" (0-10). RESULTS: FM patients
      endorsed the single deep ache question substantially more than those with chronic
      pain but without FM (7.4 +/- 2.9 vs 3.2 +/- 3.4; P < .0001) and exhibited greater
      bilateral digital evoked tenderness (6.1 +/- 3.1 vs 2.4 +/- 2.4, P < 0.0001), and
      BP-evoked pressure pain (132.6 mmHg +/-45.5 vs 169.2 mmHg +/-48.0, P < 0.0001).
      However, on multivariate logistic regressions, the BP cuff-evoked pain became non
      significant. On further analyses, a useful screening test was provided by: (1)
      pain on pinching the Achilles tendon at 4 kg/pressure over 4 seconds, and (2) and
      positive endorsement of the question "I have a persistent deep aching over most
      of my body". CONCLUSION: These results suggest that 2 tests, taking less than 1
      minute, can indicate a probable diagnosis of FM in a chronic pain patient. In the
      case of a positive screen, a follow-up examination is required for confirmation
      or refutation.

PMID- 29063664
TI  - Reducing chronic breast cancer-related lymphedema utilizing a program of
      prospective surveillance with bioimpedance spectroscopy.
AB  - This single-institution experience evaluated the use of bioimpedance spectroscopy
      to facilitate early detection and treatment of breast cancer-related lymphedema
      (BCRL) in a cohort of 596 patients (79.6% high risk). Seventy-three patients
      (12%) developed an elevated L-Dex score with axillary lymph node dissection (P <
      .001), taxane chemotherapy (P = .008), and regional nodal irradiation (P < .001)
      associated. At last follow-up, only 18 patients (3%) had unresolved clinically
      significant BCRL requiring complete decongestive physiotherapy. This rate of BCRL
      is lower than reported in contemporary studies, supporting recent NCCN guidelines
      promoting prospective screening, education and intervention for BCRL.

PMID- 29063663
TI  - Enhanced natural killer cell activity is found in exposed uninfected recipients
      of hepatitis C-contaminated blood.
AB  - A minority of injecting drug users, termed exposed uninfected, are resistant to
      hepatitis C (HCV) infection despite repeated low-dose exposures. We identify for
      the first time a cohort of blood recipients who remained uninfected despite large
      dose exposure to HCV-contaminated blood and characterize immune factors that may
      confer protection. Of 1340 blood recipients from the English Look Back database
      who were transfused HCV-contaminated blood, we identified 8 who remained
      uninfected. In these 8 exposed uninfecteds, we characterized their natural killer
      (NK) cell populations and HCV-specific T-cell responses. Findings were compared
      with 10 spontaneous resolvers of HCV infection, 10 patients with chronic HCV
      infection and 10 healthy controls. Exposed uninfecteds had significantly greater
      numbers of NK cells with the activating receptor NKp30+ on CD56bright and CD56dim
      subsets compared with other groups (P < .05). Following interleukin-2 activation,
      NK cells of exposed uninfecteds had enhanced cytotoxicity that positively
      correlated with NKp30 expression (P = .02). Differences in NKp80 and KIR2DL3
      expression were also observed. HCV-specific T-cell responses were observed in
      some exposed uninfecteds but of low amplitude. Exposure without infection
      following transfusion of HCV-contaminated blood is a very rare phenomenon and
      suggests a high level of resistance to infection. Enhanced NK cell activation and
      killing, with weak HCV-specific T-cell responses, were observed many years after
      exposure in uninfected recipients and may contribute to protection from HCV
      acquisition, although additional protective factors are being sought in this
      important cohort.

PMID- 29063662
TI  - Breast density in multiethnic women presenting for screening mammography.
AB  - Data on ethnic variations in breast density are limited and often not inclusive
      of underrepresented minorities. As breast density is associated with elevated
      breast cancer risk, investigating racial and ethnic difference may elucidate the
      observed differences in breast cancer risk among different populations. We
      reviewed breast density from initial screening of women from the Capital Breast
      Care Center and Georgetown University Hospital from 2010 to 2014. Patient
      demographics including race, age at screening, education, menopausal status, and
      body mass index were abstracted. We recorded the BI-RADS density categories: (1)
      "fatty," (2) "scattered fibroglandular densities," (3) "heterogeneously dense,"
      and (4) "extremely dense." Multivariable unconditional logistic regression was
      used to identify predictors of breast density. Density categorization was
      recorded for 2146 women over the 5-year period, comprising Blacks (n = 940),
      Hispanics (n = 893), and Whites (n = 314). Analysis of subject characteristics by
      breast density showed that high category is observed in younger, Hispanic,
      nulliparous, premenopausal, and nonobese women (t-test or chi-square test, P
      values <.0001). Obese women are 70% less likely to have high density. Being
      Hispanic, premenopausal, and nonobese were predictive of high density on logistic
      regression. In this analysis of density distribution in a diverse sample,
      Hispanic women have the highest breast density, followed by Blacks and Whites.
      Unique in our findings is women who identify as Hispanic have the highest breast
      density and lower rates of obesity. Further investigation of the impact of
      obesity on breast density, especially in the understudied Hispanic group is
      needed.

PMID- 29063665
TI  - A retrospective comparison of thoracic epidural infusion and multimodal analgesia
      protocol for pain management following the minimally invasive repair of pectus
      excavatum.
AB  - BACKGROUND: Pain management following minimally invasive repair of pectus
      excavatum is variable. We recently adopted a comprehensive multimodal analgesic
      protocol that standardizes perioperative analgesic management. We hypothesized
      that patients managed with this protocol would use more opioids postoperatively,
      have similar pain control, and shorter length of stay compared to patients
      managed with thoracic epidural infusion. AIMS: We retrospectively compared opioid
      consumption, pain scores, and length of stay between a cohort of patients managed
      with our multimodal analgesic protocol and a cohort managed with a thoracic
      epidural infusion. METHODS: This retrospective cohort comparison includes
      patients, 8 to 21 years of age, managed with either thoracic epidural infusion (n
      = 21) or multimodal analgesic protocol (n = 29) following minimally invasive
      repair of pectus excavatum from January 1, 2011 through September 15, 2015. The
      primary outcome, total daily opioid consumption in morphine equivalents, is
      presented as an average by postoperative day. Secondary outcomes included median
      daily pain score and length of stay. RESULTS: Patients were similar in age,
      weight, sex, and physical status. Patients managed with thoracic epidural
      infusion received less opioid (morphine equivalents-mg/kg) intraoperatively
      compared to multimodal analgesic protocol (difference of mean [95% confidence
      interval] 0.22 [0.16-0.28] P <= .01) but required more total opioid through
      postoperative day 3 (difference of mean [95% confidence interval] 1.2 [0.26-2.14]
      P = .01). We did not observe a difference in pain scores. Median length of stay
      was 1 day less in patients managed with multimodal analgesic protocol (difference
      of median [95% confidence interval] 1 [0.3-1.7] P = .003). CONCLUSION:
      Implementation of a standardized comprehensive multimodal analgesic protocol
      following minimally invasive repair of pectus excavatum resulted in equivalent
      analgesia with a modest reduction in length of stay when compared to thoracic
      epidural. We did not observe an opioid sparing effect in our thoracic epidural
      which may reflect technique variability.

PMID- 29063666
TI  - Dimethyl fumarate inhibits osteoclasts via attenuation of reactive oxygen species
      signalling by augmented antioxidation.
AB  - Bone destructive diseases are common worldwide and are caused by dysregulation of
      osteoclast formation and activation. During osteoclastogenesis, reactive oxygen
      species (ROS) play a role in the intracellular signalling triggered by receptor
      activator of nuclear factor-kappaB ligand (RANKL) stimulation. Previously, we
      demonstrated that induction of antioxidant enzymes by Nrf2 activation using Nrf2
      gene transfer, an ETGE-peptide or polyphenols, successfully ameliorated RANKL
      dependent osteoclastogenesis. Dimethyl fumarate (DMF) has been shown to activate
      Nrf2 signalling and has been lately used in clinical trials for neurodegenerative
      diseases. In this study, we hypothesized that Nrf2 activation by DMF would
      inhibit osteoclastogenesis and bone destruction via attenuation of intracellular
      ROS signalling through antioxidant mechanisms. RAW 264.7 cells were used as
      osteoclast progenitor cells. We found that DMF induced Nrf2 translocation to the
      nucleus, augmented Nrf2 promoter-luciferase reporter activity and increased
      antioxidant enzyme expression. Using flow cytometry, we found that DMF attenuated
      RANKL-mediated intracellular ROS generation, which resulted in the inhibition of
      RANKL-mediated osteoclastogenesis. Local DMF injection into the calvaria of male
      BALB/c mice resulted in attenuated bone destruction in lipopolysaccharide-treated
      mice. In conclusion, we demonstrated in a preclinical setting that DMF inhibited
      RANKL-mediated osteoclastogenesis and bone destruction via induction of Nrf2
      mediated transcription of antioxidant genes and consequent decrease in
      intracellular ROS levels. Our results suggest that DMF may be a promising
      inhibitor of bone destruction in diseases like periodontitis, rheumatoid
      arthritis and osteoporosis.

PMID- 29063668
TI  - Anomalous pH-Dependent Nanofluidic Salinity Gradient Power.
AB  - Previous studies on nanofluidic salinity gradient power (NSGP), where energy
      associated with the salinity gradient can be harvested with ion-selective
      nanopores, all suggest that nanofluidic devices having higher surface charge
      density should have higher performance, including osmotic power and conversion
      efficiency. In this manuscript, this viewpoint is challenged and anomalous
      counterintuitive pH-dependent NSGP behaviors are reported. For example, with
      equal pH deviation from its isoelectric point (IEP), the nanopore at pH < IEP is
      shown to have smaller surface charge density but remarkably higher NSGP
      performance than that at pH > IEP. Moreover, for sufficiently low pH, the NSGP
      performance decreases with lowering pH (increasing nanopore charge density). As a
      result, a maximum osmotic power density as high as 5.85 kW m-2 can be generated
      along with a conversion efficiency of 26.3% achieved for a single alumina
      nanopore at pH 3.5 under a 1000-fold concentration ratio. Using the rigorous
      model with considering the surface equilibrium reactions on the pore wall, it is
      proved that these counterintuitive surface-charge-dependent NSGP behaviors result
      from the pH-dependent ion concentration polarization effect, which yields the
      degradation in effective concentration ratio across the nanopore. These findings
      provide significant insight for the design of next-generation, high-performance
      NSGP devices.

PMID- 29063669
TI  - 'It is an entrustment': Broad consent for genomic research and biobanks in Sub
      Saharan Africa.
AB  - In recent years, there has been an increase in the establishment of biobanks for
      genetic and genomic studies around the globe. One example of this is the Human
      Heredity and Health in Africa Initiative (H3Africa), which has established
      biobanks in the sub-region to facilitate future indigenous genomic studies. The
      concept of 'broad consent' has been proposed as a mechanism to enable potential
      research participants in biobanks to give permission for their samples to be used
      in future research studies. However, questions remain about the acceptability of
      this model of consent. Drawing on findings from empirical research about the role
      of trust in decision-making, we argue that an account of entrustment may be an
      appropriate way of addressing current challenges of seeking consent for biobank
      research in Africa. We propose a set of key points to consider that can support
      the proposed entrustment framework.

PMID- 29063671
TI  - Magnesium supplementation: A consideration in dialysis patients.
AB  - Even though disorders of magnesium (Mg) balance are common in dialyzed patients,
      this cation is often neglected. Many factors interfere with serum magnesium
      including diet, medications (eg, antacids or phosphate binders), and the dialysis
      prescription. Mg supplementation may help reduce serum phosphate concentration,
      PTH, and interfere with vascular calcification and bone mineralization. It could
      also decrease the all-cause and cardiovascular mortalities, although the results
      of current studies are conflicting. As with many other variables that influence
      hard endpoints in nephrology, additional research directly targeting the role of
      Mg supplementation in dialyzed patients are required. Nevertheless, a current
      risk/benefit assessment suggests that supplementation of Mg targeting high normal
      serum levels may represent a plausible option to improve the outcome of dialysis
      patients.

PMID- 29063672
TI  - Molecular characterization, spatial-temporal expression and magnetic response
      patterns of iron-sulfur cluster assembly1 (IscA1) in the rice planthopper,
      Nilaparvata lugens.
AB  - The mechanisms of magnetoreception have been proposed as the magnetite-based, the
      chemical radical-pair and biocompass model, in which magnetite particles, the
      cryptochrome (Cry) or iron-sulfur cluster assembly 1 (IscA1) may be involved.
      However, little is known about the association among the molecules. Here we
      investigated the molecular characterization and the mRNA expression of IscA1 in
      different developmental stages, tissues and magnetic fields in the migratory
      brown planthopper (BPH), Nilaparvata lugens. NlIscA1 contains an open reading
      frame of 390 bp, encoding amino acids of 129, with the predicted molecular weight
      of 14.0 kDa and the isoelectric point of 9.10. Well-conserved Fe-S cluster
      binding sites were observed in the predicted protein. Phylogenetic analysis
      demonstrated NlIscA1 to be clustered into the insect's IscA1. NlIscA1 showed up
      regulated mRNA expression during the period of migration. The mRNA expression of
      NlIscA1 could be detected in all the three tissues of head, thorax and abdomen,
      with the highest expression level in the abdomen. For the macropterous migratory
      Nilaparvata lugens, mRNA expression of NlIscA1 and N. lugens cryptochrome1
      (Nlcry1) were up-regulated under the magnetic fields of 5 Gauss and 10 Gauss in
      strength (vs. local geomagnetic field), while N. lugens cryptochrome2 (Nlcry2)
      remained stable. For the brachyterous non-migratory Nilaparvata lugens, no
      significant changes were found in mRNA expression of NlIscA1, Nlcry1 and Nlcry2
      among different magnetic fields. These findings preliminarily reveal that the
      expression of NlIscA1 and Nlcry1 exhibited coordinated responses to the magnetic
      field. It suggests some potential associations among the putative magneto
      sensitive molecules of cryptochrome and iron-sulfur cluster assembly.

PMID- 29063673
TI  - Theoretical development in the context of nursing-The hidden epistemology of
      nursing theory.
AB  - This article is about nursing theories, the development of nursing knowledge and
      the underlying, hidden epistemology. The current technical-economical rationality
      in society and health care calls for a specific kind of knowledge based on a
      traditional Western, Socratic view of science. This has an immense influence on
      the development of nursing knowledge. The purpose of the article was therefore to
      discuss the hidden epistemology of nursing knowledge and theories seen in a broad
      historical context and point to an alternative epistemology for a future context.
      It is a question about which nursing theories and what nursing knowledge should
      be developed in order to benefit patients and relatives of the future. We suggest
      that future knowledge development in nursing be developed in an interchange
      between theory and practice and guided by philosophy like a kind of pendulum
      where all three elements are treated as equals. We suggest a framework for the
      development of nursing knowledge based on a caring-ethical practice, a theory on
      life phenomena in suffering and relationship-based nursing, and thereby, we may
      be able to help patients to be cured, to recover, to be alleviated or comforted
      when suffering.

PMID- 29063667
TI  - Bacterial lipoproteins and other factors released by Francisella tularensis
      modulate human neutrophil lifespan: Effects of a TLR1 SNP on apoptosis
      inhibition.
AB  - Francisella tularensis infects several cell types including neutrophils, and
      aberrant neutrophil accumulation contributes to tissue destruction during
      tularaemia. We demonstrated previously that F. tularensis strains Schu S4 and
      live vaccine strain markedly delay human neutrophil apoptosis and thereby prolong
      cell lifespan, but the bacterial factors that mediate this aspect of virulence
      are undefined. Herein, we demonstrate that bacterial conditioned medium (CM) can
      delay apoptosis in the absence of direct infection. Biochemical analyses show
      that CM contained F. tularensis surface factors as well as outer membrane
      components. Our previous studies excluded roles for lipopolysaccharide and
      capsule in apoptosis inhibition, and current studies of [14 C] acetate-labelled
      bacteria argue against a role for other bacterial lipids in this process. At the
      same time, studies of isogenic mutants indicate that TolC and virulence factors
      whose expression requires FevR or MglA were also dispensable, demonstrating that
      apoptosis inhibition does not require Type I or Type VI secretion. Instead, we
      identified bacterial lipoproteins (BLPs) as active factors in CM. Additional
      studies of isolated BLPs demonstrated dose-dependent neutrophil apoptosis
      inhibition via a TLR2-dependent mechanism that is significantly influenced by a
      common polymorphism, rs5743618, in human TLR1. These data provide fundamental new
      insight into pathogen manipulation of neutrophil lifespan and BLP function.

PMID- 29063670
TI  - Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and
      exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.
AB  - Emerging evidence indicates that irisin provides beneficial effects in diabetes.
      However, whether irisin influences the development of diabetic cardiomyopathy
      (DCM) remains unclear. Therefore, we investigated the potential role and
      mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice.
      Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic
      mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 MUg/g
      body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood
      glucose levels in the diabetic mice. However, the results of echocardiographical
      and histopathological assays indicated that low-dose irisin treatment alleviated
      cardiac fibrosis and left ventricular function in the diabetic mice, whereas high
      dose irisin failed to mitigate the ventricular function impairment and increased
      collagen deposition. The potential mechanism underlying the effect of low-dose
      irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to
      mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced
      high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling
      and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated
      DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose
      irisin disrupted normal MMP expression and induced cardiac fibroblast
      proliferation and migration, which results in excess collagen deposition. Thus,
      irisin can inhibit high glucose-induced EndMT and exert a dose-dependent
      bidirectional effect on DCM.

PMID- 29063674
TI  - Indirect osteoblast differentiation by liposomal clodronate.
AB  - Bisphosphonates impair function of osteoclasts and prevent bone resorption, the
      mechanism of which has been studied extensively. However, the possible effects of
      bisphosphonates on chondroblast differentiation and calcium deposition by
      osteoblasts have only been demonstrated recently. Moreover, cells from monocytic
      lineage are capable of stimulating osteoblast proliferation. Hence,
      susceptibility of osteoblasts to various factors requires further investigation.
      A primary culture of bone marrow-derived stromal cells was treated with liposomal
      clodronate (0.1, 0.5, or 1.0 mg/ml) or conditioned medium from liposomal
      clodronate. Liposomal clodronate (0.25 mg) was injected into mouse femur for in
      vivo experiments. The effects of liposomal clodronate were examined by alkaline
      phosphatase staining and/or activity assay, and real-time RT-PCR was used for
      studying the effect on osteogenic gene expression. Administration of liposomal
      clodronate to bone marrow-derived mesenchymal stromal cell culture enhanced
      alkaline phosphatase activity and mRNA levels of Runx2 and Dlx5. In addition,
      conditioned medium from liposomal clodronate also stimulated osteogenic
      characteristics similar to those of observed in vitro, and the number of exosomes
      in the conditioned medium was highest when pre-treated with liposomal clodronate.
      Western blot analysis revealed the presence of RANK proteins in exosomes
      collected from conditioned medium of liposomal clodronate. Identical observations
      were obtained in vivo, as liposomal clodronate-injected mouse femur showed
      increased alkaline phosphatase activity and Runx2 and Dlx5 mRNA expressions, even
      though the numbers of monocytes and macrophages were reduced. In conclusion,
      osteoblast differentiation was promoted via soluble RANK-containing exosomes in
      response to clodronates.

PMID- 29063675
TI  - Feasibility of infrared tracking of beating heart motion for robotic assisted
      beating heart surgery.
AB  - BACKGROUND: Accurate tracking of the heart surface motion is a major requirement
      for robot assisted beating heart surgery. METHOD: The feasibility of a stereo
      infrared tracking system for measuring the free beating heart motion was
      investigated by experiments on a heart motion simulator, as well as model surgery
      on a dog. RESULTS: Simulator experiments revealed a high tracking accuracy (81
      MUm root mean square error) when the capturing times were synchronized and the
      tracker pointed at the target from a 100 cm distance. The animal experiment
      revealed the applicability of the infrared tracker with passive markers in
      practical heart surgery conditions. CONCLUSION: With the current technology,
      infrared tracking with passive markers might be the optimal solution for
      accurate, fast, and reliable tracking of heart motion during robot assisted
      beating heart surgery.

PMID- 29063677
TI  - Transporters of Trypanosoma brucei-phylogeny, physiology, pharmacology.
AB  - Trypanosoma brucei comprise the causative agents of sleeping sickness, T. b.
      gambiense and T. b. rhodesiense, as well as the livestock-pathogenic T. b.
      brucei. The parasites are transmitted by the tsetse fly and occur exclusively in
      sub-Saharan Africa. T. brucei are not only lethal pathogens but have also become
      model organisms for molecular parasitology. We focus here on membrane transport
      proteins of T. brucei, their contribution to homeostasis and metabolism in the
      context of a parasitic lifestyle, and their pharmacological role as potential
      drug targets or routes of drug entry. Transporters and channels in the plasma
      membrane are attractive drug targets as they are accessible from the outside.
      Alternatively, they can be exploited to selectively deliver harmful substances
      into the trypanosome's interior. Both approaches require the targeted transporter
      to be essential: in the first case to kill the trypanosome, in the second case to
      prevent drug resistance due to loss of the transporter. By combining functional
      and phylogenetic analyses, we were mining the T. brucei predicted proteome for
      transporters of pharmacological significance. Here, we review recent progress in
      the identification of transporters of lipid precursors, amino acid permeases and
      ion channels in T. brucei.

PMID- 29063676
TI  - X-linked inhibitor of apoptosis inhibition sensitizes acute myeloid leukemia cell
      response to TRAIL and chemotherapy through potentiated induction of proapoptotic
      machinery.
AB  - Acute myeloid leukemia (AML) is an aggressive disease with an increasing
      incidence and relatively low 5-year survival rate. Unfortunately, the underlying
      mechanism of leukemogenesis is poorly known, and there has been little progress
      in the treatment for AML. Studies have shown that X-linked inhibitor of apoptosis
      (XIAP), one of the inhibitors of apoptosis proteins (IAPs), is highly expressed
      and contributes to chemoresistance in AML. Hence, a novel drug, RO6867520 (RO
      BIR2), developed by Roche targeting the BIR2 domain in XIAP to reactivate blocked
      apoptosis, is a promising therapy for AML. The monotherapy of RO-BIR2 had minimal
      effect on most of the AML cell lines tested except U-937. In contrast to AML cell
      lines, in general, RO-BIR2 alone has been shown to inhibit the proliferation of
      primary AML patient samples effectively and induced apoptosis in a dose-dependent
      manner. A combination of RO-BIR2 with TNF-related apoptosis-inducing ligand
      (TRAIL) led to highly synergistic effect on AML cell lines and AML patient
      samples. This combination therapy is capable of inducing apoptosis, thereby
      leading to an increase in specific apoptotic cell population, along with the
      activation of caspase 3/7. A number of apoptotic-related proteins such as XIAP,
      cleavage of caspase 3, cleavage of caspase 7, and cleaved PARP were changed upon
      combination therapy. Combination of RO-BIR2 with Ara-C had similar effect as the
      TRAIL combination. Ara-C combination also led to synergistic effect on AML cell
      lines and AML patient samples with low combination indexes (CIs). We conclude
      that the combination of RO-BIR2 with either TRAIL or Ara-C represents a potent
      therapeutic strategy for AML and is warranted for further clinical trials to
      validate the synergistic benefits in patients with AML, especially for the
      elderly who are abstaining from intensive chemotherapy.

PMID- 29063679
TI  - Estrogen receptor mutations and splice variants determined in liquid biopsies
      from metastatic breast cancer patients.
AB  - Mutations and splice variants in the estrogen receptor (ER) gene, ESR1, may yield
      endocrine resistance in metastatic breast cancer (MBC) patients. These putative
      endocrine resistance markers are likely to emerge during treatment, and
      therefore, its detection in liquid biopsies, such as circulating tumor cells
      (CTCs) and cell-free DNA (cfDNA), is of great interest. This research aimed to
      determine whether ESR1 mutations and splice variants occur more frequently in
      CTCs of MBC patients progressing on endocrine treatment. In addition, the
      presence of ESR1 mutations was evaluated in matched cfDNA and compared to CTCs.
      CellSearch-enriched CTC fractions (>=5/7.5 mL) of two MBC cohorts were evaluated,
      namely (a) patients starting first-line endocrine therapy (n = 43, baseline
      cohort) and (b) patients progressing on any line of endocrine therapy (n = 40,
      progressing cohort). ESR1 hotspot mutations (D538G and Y537S/N/C) were evaluated
      in CTC-enriched DNA using digital PCR and compared with matched cfDNA (n = 18
      baseline cohort; n = 26 progressing cohort). Expression of ESR1 full-length and 4
      of its splice variants (?5, ?7, 36 kDa, and 46 kDa) was evaluated in CTC-enriched
      mRNA. It was observed that in the CTCs, the ESR1 mutations were not enriched in
      the progressing cohort (8%), when compared with the baseline cohort (5%) (P =
      0.66). In the cfDNA, however, ESR1 mutations were more prevalent in the
      progressing cohort (42%) than in the baseline cohort (11%) (P = 0.04). Three of
      the same mutations were observed in both CTCs and cfDNA, 1 mutation in CTCs only,
      and 11 in cfDNA only. Only the ?5 ESR1 splice variant was CTC-specific expressed,
      but was not enriched in the progressing cohort. In conclusion, sensitivity for
      detecting ESR1 mutations in CTC-enriched fractions was lower than for cfDNA. ESR1
      mutations detected in cfDNA, rarely present at the start of first-line endocrine
      therapy, were enriched at progression, strongly suggesting a role in conferring
      endocrine resistance in MBC.

PMID- 29063680
TI  - Development of a physical shoulder simulator for the training of basic
      arthroscopic skills.
AB  - BACKGROUND: Orthopaedic training programs are incorporating arthroscopic
      simulations into their residency curricula. There is a need for a physical
      shoulder simulator that accommodates lateral decubitus and beach chair positions,
      has realistic anatomy, allows for an objective measure of performance and
      provides feedback to trainees. METHODS: A physical shoulder simulator was
      developed for training basic arthroscopic skills. Sensors were embedded in the
      simulator to provide a means to assess performance. Subjects of varying skill
      level were invited to use the simulator and their performance was objectively
      assessed. RESULTS: Novice subjects improved their performance after practice with
      the simulator. A survey completed by experts recognized the simulator as a
      valuable tool for training basic arthroscopic skills. CONCLUSIONS: The physical
      shoulder simulator helps train novices in basic arthroscopic skills and provides
      objective measures of performance. By using the physical shoulder simulator,
      residents could improve their basic arthroscopic skills, resulting in improved
      patient safety.

PMID- 29063678
TI  - Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and
      CDK9 inhibitor.
AB  - Deregulation of the cyclin-dependent kinases (CDKs) has been implicated in the
      pathogenesis of multiple cancer types. Consequently, CDKs have garnered intense
      interest as therapeutic targets for the treatment of cancer. We describe herein
      the molecular and cellular effects of CCT068127, a novel inhibitor of CDK2 and
      CDK9. Optimized from the purine template of seliciclib, CCT068127 exhibits
      greater potency and selectivity against purified CDK2 and CDK9 and superior
      antiproliferative activity against human colon cancer and melanoma cell lines. X
      ray crystallography studies reveal that hydrogen bonding with the DFG motif of
      CDK2 is the likely mechanism of greater enzymatic potency. Commensurate with
      inhibition of CDK activity, CCT068127 treatment results in decreased
      retinoblastoma protein (RB) phosphorylation, reduced phosphorylation of RNA
      polymerase II, and induction of cell cycle arrest and apoptosis. The
      transcriptional signature of CCT068127 shows greatest similarity to other small
      molecule CDK and also HDAC inhibitors. CCT068127 caused a dramatic loss in
      expression of DUSP6 phosphatase, alongside elevated ERK phosphorylation and
      activation of MAPK pathway target genes. MCL1 protein levels are rapidly
      decreased by CCT068127 treatment and this associates with synergistic
      antiproliferative activity after combined treatment with CCT068127 and ABT263, a
      BCL2 family inhibitor. These findings support the rational combination of this
      series of CDK2/9 inhibitors and BCL2 family inhibitors for the treatment of human
      cancer.

PMID- 29063681
TI  - Oxidative stress and its possible relation to lower urinary tract functional
      pathology.
AB  - Oxidative stress is considered to reflect an imbalance between the systemic
      manifestation of reactive oxygen and nitrogen species (RONS) and a biological
      system's ability to readily detoxify the reactive intermediates or to repair the
      resulting damage. RONS are not only harmful agents that cause oxidative damage in
      pathologies; they also have important roles as regulatory agents in a range of
      biological phenomena. They are normally generated as by-products of oxygen
      metabolism; however, environmental stressors (i.e., ultraviolet radiation,
      ionizing radiations, pollutants, heavy metal, and xenobiotics) contribute to
      greatly increase RONS production. Several antioxidants have been exploited in
      recent years for their actual or supposed beneficial effect against oxidative
      stress, but to date, none has been approved for any indication because they have
      not met the criteria of efficacy for drug approval. The present review discusses
      the concept of oxidative stress, how to measure it, how to prevent it, and its
      occurrence in different organ systems with special reference to the lower urinary
      tract.

PMID- 29063682
TI  - Early discharge and post-discharge outcomes in patients undergoing radical
      cystectomy for bladder cancer.
AB  - OBJECTIVE: To assess whether discharging patients early after radical cystectomy
      (RC) is associated with an increased risk of readmission and post-discharge
      complications. MATERIALS AND METHODS: The National Surgical Quality Improvement
      Program database was queried to identify patients who underwent an elective RC
      from 2012 to 2015. Patients were stratified into two groups: those with a length
      of hospital stay (LOS) of 4-5 days (early-discharge group) and those with an LOS
      of 6-9 days (routine-discharge group). We used multivariable logistic regression
      analyses to assess the impact of early discharge on 30-day readmission and post
      discharge complication rates. Sensitivity analyses and subgroup analyses were
      performed to validate the robustness of our primary analyses. RESULTS: A total of
      3 311 patients were included. Unadjusted outcomes comparison showed no difference
      in readmission rate (21.6% vs 23.0%) or post-discharge complication rate (17.7%
      vs 19.6%) between the early-discharge and the routine-discharge group.
      Multivariable logistic regression also showed that early discharge was not
      associated with increased odds of readmission (odds ratio [OR] 1.00, 95%
      confidence interval [CI] 0.82-1.22; P = 1.000) or post-discharge complications
      (OR 0.95, 95% CI 0.77-1.17; P = 0.616). Two-step sensitivity analyses (excluding
      patients with LOS of 8-9 days, followed by patients with any pre-discharge
      adverse event) validated the robustness of our primary analyses. Subgroup
      analyses also yielded similar results in all subgroups except for the subgroup of
      patients aged >=85 years. CONCLUSIONS: Early discharge after RC was not
      associated with increased readmissions or post-discharge complications. Future
      prospective studies, with defined peri-operative care pathways, are needed to
      identify potential components that may enable hospitals to discharge patients
      early without compromising post-discharge outcomes.

PMID- 29063683
TI  - Skin contact with a stinging tree requiring intensive care unit admission.

PMID- 29063684
TI  - In search of a better patch test concentration for povidone-iodine.

PMID- 29063685
TI  - A new application for epoxy resins resulting in occupational allergic contact
      dermatitis: the three-dimensional printing industry.

PMID- 29063686
TI  - Active sensitization to cadmium, tin, and indium.

PMID- 29063687
TI  - Erythema multiforme-like reaction resulting from vitamin K1 oxide (phytomenadione
      epoxide).

PMID- 29063688
TI  - Allergic contact stomatitis caused Salvadora persica in toothpaste.

PMID- 29063689
TI  - Concomitant immediate and delayed sensitization by philodendron (Philodendron
      scandens) in a plant keeper.

PMID- 29063690
TI  - Intractable pruritus with chronic eczema in an elderly patient caused by long
      term intake of calcium channel blocker.

PMID- 29063691
TI  - Editorial.

PMID- 29063692
TI  - Hand dermatitis: hand hygiene consequences among healthcare workers.

PMID- 29063693
TI  - Occupational allergic contact dermatitis caused by isothiazolinones in ultrasound
      gel: 2 cases.

PMID- 29063694
TI  - Linear eczema on the amputation stump as a clinical clue to the diagnosis.

PMID- 29063696
TI  - Airborne contact dermatitis in a patient with type I and IV sensitivity to
      chicory.

PMID- 29063695
TI  - Occupational contact dermatitis caused by hydrogenated formaldehyde-benzenamine
      polymer (FBAP) in epoxy hardeners.

PMID- 29063697
TI  - Erythema multiforme-like eruption induced by risedronate.

PMID- 29063698
TI  - Exploring barriers and enablers for scaling up a community-based grain bank
      intervention for improved infant and young child feeding in Ethiopia: A
      qualitative process evaluation.
AB  - Child malnutrition remains high in Ethiopia, and inadequate complementary feeding
      is a contributing factor. In this context, a community-based intervention was
      designed to provide locally made complementary food for children 6-23 months,
      using a bartering system, in four Ethiopian regions. After a pilot phase, the
      intervention was scaled up from 8 to 180 localities. We conducted a process
      evaluation to determine enablers and barriers for the scaling up of this
      intervention. Eight study sites were selected to perform 52 key informant
      interviews and 31 focus group discussions with purposely selected informants. For
      analysis, we used a framework describing six elements of successful scaling up:
      socio-political context, attributes of the intervention, attributes of the
      implementers, appropriate delivery strategy, the adopting community, and use of
      research to inform the scale-up process. A strong political will, alignment of
      the intervention with national priorities, and integration with the health care
      system were instrumental in the scaling up. The participatory approach in
      decision-making reinforced ownership at community level, and training about
      complementary feeding motivated mothers and women's groups to participate.
      However, the management of the complex intervention, limited human resources, and
      lack of incentives for female volunteers proved challenging. In the bartering
      model, the barter rate was accepted, but the bartering was hindered by
      unavailability of cereals and limited financial and material resources to
      contribute, threatening the project's sustainability. Scaling up strategies for
      nutrition interventions require sufficient time, thorough planning, and
      assessment of the community's capacity to contribute human, financial, and
      material resources.

PMID- 29063700
TI  - Employment for radiation oncologists in Australia and New Zealand: Recent
      graduates survey of experiences and perspectives.
AB  - INTRODUCTION: This paper reports the key findings of the first survey of recent
      Radiation Oncology graduates in Australia, New Zealand (ANZ) and Singapore. It
      explores their experiences in entering the workforce, challenges and
      perspectives. METHODS: The survey was conducted in April and May 2016 focusing on
      graduates from 2013 to 2015. The questions related to relocation, current
      employment, experiences in finding a job, intentions regarding rural work, job
      satisfaction and perceptions of the job market. RESULTS: The response rate was
      80% (66/83). Most respondents (72.7%) commenced and completed their training in
      the same location. The large majority of respondents (91%) were employed with 51%
      as consultants, 20% as fellows and 15% as locums. Sixty-four percent of
      respondents spent more than twelve weeks looking for a consultant position, but
      this was expected by 80% of respondents. Seventy-three percent of respondents
      spent more than four weeks looking for a fellowship position, but this was
      expected by 90%. Twenty seven percent of respondents lived and worked in a rural
      area with nearly half of respondents who did not work in a rural area, indicating
      they would consider so if certain conditions were met. The large majority (75%)
      were satisfied with their current employment with only seven percent reporting
      dissatisfaction. Respondents felt that the job market was very competitive
      because of the large number of trainees and better workforce planning was
      required to ensure a reasonable balance between workforce supply and demand. Some
      career guidance and mentorship for readiness for the job market was thought to be
      beneficial. CONCLUSIONS: This initial survey of recent Radiation Oncology
      graduates in ANZ and Singapore has revealed the large majority are employed as
      consultants or fellows, although there is apprehension about a competitive job
      market. The survey should be repeated on a regular basis to monitor future
      trends.

PMID- 29063699
TI  - Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) from
      Staphylococcus lugdunensis.
AB  - The 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine
      monophosphate (IMP) cyclohydrolase (ATIC) catalyzes final two steps of purine
      nucleotide de novo biosynthetic pathway. This study reports the characterization
      of ATIC from Staphylococcus lugdunensis (SlugATIC). Apart from kinetic analysis
      and a detailed biophysical characterization of SlugATIC, the role of ATIC in cell
      proliferation has been demonstrated for the first time. The purified recombinant
      SlugATIC and its truncated domains exist mainly in dimeric form was revealed in
      gel-filtration and glutaraldehyde cross-linking studies. The two activities
      reside on separate domains was demonstrated in kinetic analysis of SlugATIC and
      reconstituted truncated N-terminal IMP cyclohydrolase (IMPCHase) and C-terminal
      AICAR transformylase (AICAR TFase) domains. Site-directed mutagenesis showed that
      Lys255 and His256 are the key catalytic residues, while Asn415 substantially
      contributes to AICAR TFase activity in SlugATIC. The differential scanning
      calorimetry (DSC) analysis revealed a molten globule-like structure for
      independent N-terminal domain as compared with a relatively stable conformational
      state in full-length SlugATIC signifying the importance of covalently linked
      domains. Unlike reported crystal structures, the DSC studies revealed significant
      conformational changes on binding of leading ligand to AICAR TFase domain in
      SlugATIC. The cell proliferation activity of SlugATIC was observed where it
      promoted proliferation and viability of NIH 3T3 and RIN-5F cells, exhibited in
      vitro wound healing in NIH 3T3 fibroblast cells, and rescued RIN-5F cells from
      the cytotoxic effects of palmitic acid and high glucose. The results suggest that
      ATIC, an important drug target, can also be exploited for its cell proliferative
      properties.

PMID- 29063701
TI  - Jealousy and relationship satisfaction among Indonesian dating adults.
AB  - This study aimed to explore the link between jealousy and relationship
      satisfaction among dating adults in Indonesia. A survey of 150 adults showed
      that, while the overall level of jealousy was not significantly correlated with
      relationship satisfaction, correlations exist between relationship satisfaction
      and certain aspects of jealousy.

PMID- 29063702
TI  - Antiresorptive treatment-associated ONJ.
AB  - Osteonecrosis of the jaw (ONJ) is a severe complication of therapy with
      antiresorptive agents (e.g. bisphosphonates and denosumab), which are used to
      manage bone metastases from cancer, to reduce the incidence of skeletal-related
      events. Available data indicate that 0-27, 5% of patients exposed to
      antiresorptive agents may develop ONJ, depending on the number of infusions and
      the duration of therapy. Besides antiresorptive therapy, a number of risk factors
      for osteonecrosis have been identified. Oral surgical procedures, tooth
      extractions and infection to the jawbones are considered the main risk factors
      for developing ONJ, when receiving antiresorptive therapy. However, a growing
      number of patients develop ONJ without apparent risk factors, raising concern for
      other predisposing factors. Jaw bone necrosis may be irreversible, resulting in a
      chronic disease with negative impact on the quality of patients' lives. The role
      of risk reduction strategies like meticulous dental screening and optimal oral
      hygiene is fundamental for preventing development of ONJ. ONJ is usually treated
      conservatively to relieve the symptoms and manage jaw bone necrosis. In certain
      cases, surgical intervention is required. Future research should emphasize
      individual predisposition to ONJ, more effective preventive measures and more
      efficient therapeutic procedures.

PMID- 29063703
TI  - Analysis of retinal layer thickness in diabetic macular oedema treated with
      ranibizumab or triamcinolone.
AB  - PURPOSE: To evaluate detailed changes in retinal layer thickness in spectral
      domain optical coherence tomography (SD-OCT) images during a 1-year follow-up of
      patients treated for diabetic macula oedema (DME). METHODS: Post hoc analysis of
      retinal layer thickness changes applying the automated layer segmentation of SD
      OCT images in eyes with DME that were randomly assigned to receive pro re nata
      (PRN) treatment with either 0.5 mg ranibizumab or 8 mg triamcinolone. In each
      patient, seven retinal layers were segmented in 49 scans covering a 20 degrees  *
      20 degrees  area of the macula at baseline and after 1 year of treatment. Changes
      in individual layer thickness were correlated with visual acuity (VA) and
      compared between treatment arms. RESULTS: Twenty-five patients (seven female,
      60.2 +/- 15.1 years) were evaluated. Thickness decrease of retinal nerve fibre
      layer (RNFL) was associated with a gain in VA over 12 months (r > 0.54; p <
      0.05). Decrease in ganglion cell layer (GCL) and GCL+IPL thickness pooled for
      nasal Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields correlated
      with VA as follows: ranibizumab r = 0.74 (GCL) and r = 0.63 (GCL+IPL); and
      triamcinolone r = 0.45 (GCL) and r = 0.46 (GCL+IPL). CONCLUSION: In DME therapy,
      reduction in RNFL thickness may have a considerable impact on retinal function,
      unrelated to the type of pharmacological treatment. Precise morphologic
      quantification of neurosensory layers by SD OCT offers new insight into disease
      pathology and therapeutic targets.

PMID- 29063704
TI  - Way-finding strategies of blind persons in urban scale.
AB  - The aim of this study was to determine whether urban environments with different
      prominent sensory inputs have an impact on the way-finding strategies of blind
      people and to identify these impacts, where applicable. We specifically
      investigated how blind people use their senses to compensate for the lack of
      visual information and how the priority of senses changes according to the urban
      context. The participants of the study consisted of nine congenitally blind
      individuals and the study took place in two urban settings: a dense urban
      district, Kemeralti district in Izmir; and an urban park, the Izmir Fair Park.
      During the learning phase, a first trial along the selected routes was conducted
      for each participant individually along with one of the researchers. In the test
      phase, the participants were requested to re-walk the route and verbally report
      the environmental cues they attended to. The participants' verbal reports were
      recorded and transcripts of the recordings were coded according to the
      environmental sensory inputs. In addition, the short-term memory of each
      participant was also evaluated. The results show that the characteristics of the
      urban environment seem to have an impact on way-finding strategies of blind
      individuals. It was found that the sound of the city and the echo from the
      environment are the most important factors for blind participants in the dense
      urban environment. Environmental boundaries provided echoes and gave a sense of
      enclosure that helped them orient themselves, whereas, in the park environment,
      the sense of enclosure was not enhanced due to a lack of boundaries in the
      environment.

PMID- 29063706
TI  - Relationship Between Mortality and Cancer-Bearing Status in Patients With Chronic
      Kidney Disease Who Attended an Educational Program.
AB  - Patients with malignancy have a poorer prognosis than others do, which must be
      taken into consideration when treating them for chronic kidney disease (CKD).
      However, there are few studies investigating their prognosis. This was an
      observational study of 515 (394 men and 121 women) stable non-dialysis patients
      with CKD who attended a CKD educational program. Mean age was 68.8 +/- 13.0
      years. Median follow-up was 968.5 days. Mean creatinine was 3.4 +/- 1.6 mg/dL. Of
      these, 63 had malignancy and 452 did not; 20.6% of the former and 11.9% of the
      latter group died by the end of the study period (P = 0.0548). Malignancy was not
      associated with all-cause mortality (HR: 1.3475, 95% CI: 0.7202-2.5214, P =
      0.3507) but with malignancy-associated mortality (HR: 3.9477, 95% CI: 1.6348
      9.5331, P = 0.0023). Renal replacement therapy was not associated with mortality.
      Since malignancy greatly affects the prognosis, it must be taken into
      consideration when treating these patients.

PMID- 29063707
TI  - Pulmonary cryptococcosis diagnosed on a lung fine-needle aspiration.

PMID- 29063705
TI  - Refinement of the subunit interaction network within the nucleosome remodelling
      and deacetylase (NuRD) complex.
AB  - : The nucleosome remodelling and deacetylase (NuRD) complex is essential for the
      development of complex animals. NuRD has roles in regulating gene expression and
      repairing damaged DNA. The complex comprises at least six proteins with two or
      more paralogues of each protein routinely identified when the complex is purified
      from cell extracts. To understand the structure and function of NuRD, a map of
      direct subunit interactions is needed. Dozens of published studies have attempted
      to define direct inter-subunit connectivities. We propose that conclusions
      reported in many such studies are in fact ambiguous for one of several reasons.
      First, the expression of many NuRD subunits in bacteria is unlikely to lead to
      folded, active protein. Second, interaction studies carried out in cells that
      contain endogenous NuRD complex can lead to false positives through bridging of
      target proteins by endogenous components. Combining existing information on NuRD
      structure with a protocol designed to minimize false positives, we report a
      conservative and robust interaction map for the NuRD complex. We also suggest a
      3D model of the complex that brings together the existing data on the complex.
      The issues and strategies discussed herein are also applicable to the analysis of
      a wide range of multi-subunit complexes. ENZYMES: Micrococcal nuclease (MNase),
      EC 3.1.31.1; histone deacetylase (HDAC), EC 3.5.1.98.

PMID- 29063708
TI  - Haematological indices and haematinic levels after mini gastric bypass: a matched
      comparison with Roux-en-Y gastric bypass.
AB  - Many surgeons believe mini gastric bypass (MGB) is more likely to cause
      micronutrient malabsorption compared to Roux-en-Y gastric bypass (RYGB). Till
      date, there is no published study evaluating haematological indices and
      haematinic levels in patients undergoing MGB and comparing these with a matched
      cohort of RYGB. Two hundred patients who underwent MGB between October 2012 and
      October 2015 were matched to 200 patients who underwent RYGB for age, sex, body
      mass index and time of surgery. We then compared haemoglobin, mean corpuscular
      volume, iron, ferritin, vitamin B12 and folic acid levels preoperatively and at 6
      monthly intervals after surgery until 2 years. The percentage total weight loss
      was significantly higher in the MGB group compared to the RYGB group at all time
      points. At 2 years, MGB and RYGB both led to an increase in anaemia rates but the
      difference was only significant for MGB group. Compared to RYGB, MGB patients
      were more likely to be anaemic at 2 years, although the difference was not
      significant statistically (16.6% vs. 12.7%; P value = 0.55). There was a trend
      for lower iron and folate levels in MGB group compared to RYGB group but the
      difference was statistically significant at some of the time periods only
      (significantly lower folate at 6 and 12 months and lower iron at 6 months in the
      MGB group). MGB leads to a significant increase in anaemia rates in a
      supplemented cohort. There is a trend towards lower iron and folate levels and
      higher anaemia rates in MGB group in comparison with RYGB. Larger studies with
      longer follow-up should evaluate results of MGB with a shorter biliopancreatic
      limb.

PMID- 29063710
TI  - Adaptive social impact management for conservation and environmental management.
AB  - Concerns about the social consequences of conservation have spurred increased
      attention the monitoring and evaluation of the social impacts of conservation
      projects. This has resulted in a growing body of research that demonstrates how
      conservation can produce both positive and negative social, economic, cultural,
      health, and governance consequences for local communities. Yet, the results of
      social monitoring efforts are seldom applied to adaptively manage conservation
      projects. Greater attention is needed to incorporating the results of social
      impact assessments in long-term conservation management to minimize negative
      social consequences and maximize social benefits. We bring together insights from
      social impact assessment, adaptive management, social learning, knowledge
      coproduction, cross-scale governance, and environmental planning to propose a
      definition and framework for adaptive social impact management (ASIM). We define
      ASIM as the cyclical process of monitoring and adaptively managing social impacts
      over the life-span of an initiative through the 4 stages of profiling, learning,
      planning, and implementing. We outline 14 steps associated with the 4 stages of
      the ASIM cycle and provide guidance and potential methods for social-indicator
      development, predictive assessments of social impacts, monitoring and evaluation,
      communication of results, and identification and prioritization of management
      responses. Successful ASIM will be aided by engaging with best practices -
      including local engagement and collaboration in the process, transparent
      communication of results to stakeholders, collective deliberation on and choice
      of interventions, documentation of shared learning at the site level, and the
      scaling up of insights to inform higher-level conservation policies-to increase
      accountability, trust, and perceived legitimacy among stakeholders. The ASIM
      process is broadly applicable to conservation, environmental management, and
      development initiatives at various scales and in different contexts.

PMID- 29063709
TI  - Pitfalls in diagnosis with the use of circulating tumor-derived epidermal growth
      factor receptor mutations in lung cancer harboring pretreatment T790M.
AB  - The circulating tumor DNA (ctDNA) assay has recently been approved for the
      selection of EGFR-tyrosine kinase inhibitors as first-line treatment in lung
      cancer. However, it remains to be determined whether this assay can detect all
      complex EGFR mutations within a single tumor. We report a case of an elderly
      woman with stage IV lung adenocarcinoma, in which EGFR mutation assays detected
      L858R and pretreatment T790M from a tissue biopsy. In contrast, the circulating
      tumor DNA assay detected L858R, but not pretreatment T790M in the plasma,
      regardless of the fact that similar amounts of each mutation were present in the
      biopsy specimen. Treatment with afatinib was not effective, but subsequent
      treatment with osimertinib remarkably regressed the tumor. Our findings indicate
      that physicians should accurately evaluate EGFR-tyrosine kinase inhibitor
      insensitive mutations using tissue samples in the first-line setting, even when
      L858R and exon 19 deletions are detected in the plasma.

PMID- 29063711
TI  - Role of ultrasound measuring position and ventilation pressure in determining
      correct tube size in children.
AB  - BACKGROUND: Ultrasound measurements of the airway are useful for determining
      correctly sized, uncuffed endotracheal tubes in children. AIMS: The primary
      objective of this study was to evaluate the influence of ventilation pressure on
      the sonographically measured tracheal diameter at different levels. METHODS: A
      total of 100 patients (under 7 years) were enrolled in this study. Six
      sonographic measurements of minimal transverse diameters at 3 locations (vocal
      chords, cricoid cartilage, and proximal trachea) and at 2 different ventilation
      pressures (0 and 15 mbar) were performed before the intubation procedure. The
      intubating anesthesiologists were blinded to the results of the ultrasound
      measurements. The rate of agreement of the outer diameter of the correctly sized
      endotracheal tube (reference) with the 6 sonographic diameters was determined. In
      addition, the correct tube sizes were compared with the results of traditional
      prediction methods (Penlington's and Cole's formula in children >=1 year and a
      decision table in children <1 year). RESULTS: Best rate of agreement resulted
      from cricoid cartilage (70% and 83% at 0 and 15 mbar). CONCLUSION: The airway
      level selected for ultrasound and airway pressure during measurement determines
      the rate of agreement between the measurement result and correct ETT size.

PMID- 29063712
TI  - The possible causal relationship between fragmentation of genomic DNA and
      formation of viable, but non-culturable probiotic bacteria upon storage in dry
      state.
AB  - In this study, the aim was to establish if loss of DNA integrity is a cause of
      loss of culturability for probiotic bacteria during storage in dry state. The
      number of colony forming units (CFU), number of metabolically active cells, and
      DNA integrity during dry storage of probiotic strains, B. animalis subsp. lactis
      BB-12 and L. acidophilus LA-5, were investigated. The probiotic strains were
      freeze-dried and stored at 20 degrees C, with and without oxygen present, and at
      water activity levels 0.22 or 0.32. Dry storage resulted in a decrease in CFU
      during the entire storage period. The number of metabolically active cells was
      unchanged during storage of B. animalis subsp. lactis BB-12, but did decrease
      during the first week of storage of L. acidophilus LA-5. Loss of DNA integrity
      was evident for both strains during storage and correlated well with the loss of
      CFU. Both loss of CFU and loss of DNA integrity were significantly greater for
      both strains when oxygen was present and when aw was increased. Statistical
      analysis indicates a possible causal relationship between DNA degradation and
      loss of culturability and this idea is consistent with the function of DNA at
      cell division. The study contributes with new knowledge of the cause for loss of
      CFU during dry storage of probiotic bacteria, which possibly can aid in the
      improvement of preservation techniques. (c) 2017 American Institute of Chemical
      Engineers Biotechnol. Prog., 34:231-242, 2018.

PMID- 29063714
TI  - Factorization of Force and Timing in Sensorimotor Performance: Long-Range
      Correlation Properties of Two Different Task Goals.
AB  - Long-range correlations are often manifested in the form of 1/fbeta noise in a
      series of repeated measurements of the same neural or behavioral variable. Recent
      work has demonstrated that the magnitude and nature of these long-range
      correlations reliably capture individual differences and variation in task
      performance. In sensorimotor timing experiments, task characteristics such as
      tapping or circle drawing affect these long-range correlations during the
      production of isochronous time intervals. Such correlations are highly
      reproducible across multiple trials for the same task but do not correlate
      between tasks. In the present experiment, we investigate whether two behavioral
      variables that are simultaneously controlled by the same participant in a given
      experimental condition can show such differentially organized fluctuations. In
      order to answer this question, 13 participants were asked to produce repetitive
      movements with their right index finger at a specified time interval (500 ms) and
      a specified force (8N) in the absence of an auditory metronome and visual
      feedback of force levels following a synchronization-continuation paradigm.
      Although participants showed high levels of consistency in the long-range
      correlations for each task component separately over multiple
      trials/observations, the long-range fluctuations for force and timing were found
      to show no correlations with each other for each participant. Cross recurrence
      quantification analyses (CRQA) revealed that there was limited shared structure
      between the timing and force time series data. Taken together, these results
      suggest that complex systems can organize multiple processes in a relatively
      independent manner while maintaining a high degree of reliability within one task
      parameter.

PMID- 29063715
TI  - Comparative Aspects of Pre- and Postnatal Development of the Male Reproductive
      System.
AB  - This review describes pre- and postnatal development of the male reproductive
      system in humans and laboratory animals, and highlights species differences in
      the timing and control of hormonal and morphologic events. Major differences are
      that the fetal testis is dependent on gonadotropins in humans, but is independent
      of such in rats; humans have an extended postnatal quiescent period, whereas rats
      exhibit no quiescence; and events such as secretion by the prostate and seminal
      vesicles, testicular descent, and the appearance of spermatogonia are all
      prenatal events in humans, but are postnatal events in rats. Major differences in
      the timing of the developmental sequence between rats and humans include:
      gonocyte transformation period (rat: postnatal day 0-9; human: includes
      gestational week 22 to 9 months of age); masculinization programming window (rat:
      gestational day 15.5-17.5; human: gestational week 9-14); and mini-puberty (rat:
      0-6 hr after birth; human: 3-6 months of age). Endocrine disruptors can cause
      unique lesions in the prenatal and early postnatal testis; therefore, it is
      important to consider the differences in the timing of the developmental sequence
      when designing preclinical studies as identification of windows of sensitivity
      for endocrine disruption or toxicants will aid in interpretation of results and
      provide clues to a mode of action. Birth Defects Research 110:190-227, 2018. (c)
      2017 Wiley Periodicals, Inc.

PMID- 29063713
TI  - Cognition and the course of prodromal Parkinson's disease.
AB  - BACKGROUND: Prospective data on cognition in prodromal Parkinson's disease are
      limited. The objectives of this study were to assess in prodromal PD (1) if
      baseline cognition predicts conversion to clinical PD, (2) if baseline dopamine
      transporter binding predicts longitudinal changes in cognition, and (3) if
      impaired olfaction predicts future cognitive decline. METHODS: Prodromal
      participants were 136 hyposmic individuals enrolled in the Parkinson Associated
      Risk Study. We examined baseline neuropsychological test performance in PD
      converters versus nonconverters and the association between baseline dopamine
      transporter binding and change in cognition. An additional 73 normosmic
      individuals were included in analyses of the relationship between hyposmia and
      cognitive decline. RESULTS: In prodromal participants, baseline cognitive scores
      did not significantly predict conversion, but converters performed numerically
      worse on 5 of the 6 cognitive domains assessed, with the greatest differences in
      executive function/working memory (0.68 standard deviation lower) and global
      cognition (0.64 standard deviation lower). Lower baseline dopamine transporter
      binding predicted greater future decline in processing speed/attention (P =
      0.02). Hyposmia predicted greater future decline in language (P = 0.005) and
      memory (P = 0.01) abilities. CONCLUSIONS: Given hyposmia in the general
      population predicts cognitive decline, the role of cognition in predicting
      conversion in prodromal PD needs to be assessed in large cohorts followed long
      term. The dopamine system may be associated with changes in processing
      speed/attention in individuals at risk for PD. (c) 2017 International Parkinson
      and Movement Disorder Society.

PMID- 29063717
TI  - Chemical Fixation of CO2 and Other Heterogeneous Catalytic Studies by Employing a
      Layered Cu-Porphyrin Prepared Through Single-Crystal to Single-Crystal Exchange
      of a Zn Analogue.
AB  - A solvothermal reaction of Zn(NO3 )2 ?6 H2 O, tetra-(4-pyridyl)porphyrin (H2
      TPyP), and 4,4'-oxybis(benzoic acid) (H2 OBA) resulted in a new two-dimensional
      Zn- porphyrin metal-organic framework compound, [Zn2 (C40 H24 N8 )0.5 (C14 H8 O5
      )(DMA)](DMA)(H2 O)6 (1; DMA=N,N-dimethylacetamide). The ZnII ions present in 1
      could be exchanged by using a solution of Cu(NO3 )2 ?3 H2 O in DMA at room
      temperature to give [Cu2 (C40 H24 N8 )0.5 (C14 H8 O5 )(DMA)](DMA)(H2 O)3 (Cu?1).
      The extra-framework solvent molecules have been shown to be reversibly removed or
      exchanged without collapse of the framework. Solvent-free Cu?1 was explored as an
      active heterogeneous catalyst towards three different organic reactions: 1) the
      chemical fixation of CO2 into cyclic carbonate at room temperature and 1 atm; 2)
      the nitroaldol reaction under solvent-free conditions, and 3) the three-component
      coupling of aminopyridine, benzaldehyde, and aryl alkynes followed by 5-exo-dig
      cyclization to produce the important pharmacophore imidazopyridine.

PMID- 29063716
TI  - Variations in demand and provision for publicly funded outpatient musculoskeletal
      physiotherapy services across Quebec, Canada.
AB  - RATIONALE: The prevalence of musculoskeletal disorders is high and expected to
      increase in the next decade. Persons suffering from musculoskeletal disorders
      benefit from early physiotherapy services. However, access to publicly funded
      physiotherapy services has been shown to be compromised by long waiting times and
      limited availability of resources in many countries around the world. Decisions
      on resource allocation may create geographic disparities in provision and access
      to services, which may result in inequity in access. AIMS AND OBJECTIVES: This
      study aimed to assess variations in demand and provision of publicly funded
      outpatient physiotherapy services across the province of Quebec, Canada, as well
      as to assess the demand to provision relationship. METHODS: We conducted a
      secondary analysis of data retrieved from the 2008 Quebec Health Survey and data
      obtained from a survey of hospitals in the province of Quebec in 2015. We used
      geographic information systems analyses and descriptive analyses to assess
      geographic variations and the relationship between demand and provision. RESULTS:
      Our results indicate substantial variations in the provision and demand for
      physiotherapy services in the province of Quebec. The variations in service
      provision did not follow the variations in demand. Long waiting times and
      insufficient provision of services were found in many regions. CONCLUSIONS: The
      variations in provision of physiotherapy services between regions reported in our
      study did not correspond to the variations in demand. Such geographic variations
      and demand to provision mismatches may create inequity in access to services,
      especially for those unable to afford private services.

PMID- 29063718
TI  - GLUT1 -mediated venlafaxine-thiamine disulfide system-glucose conjugates with
      "lock-in" function for central nervous system delivery.
AB  - Venlafaxine, a novel third-generation antidepressant drug, has been described as
      a reference treatment for major depression, owing to its ability of inhibiting
      both noradrenalin and serotonin neuronal reuptake, and inhibiting dopamine
      reuptake slightly. However, its clinical application is hampered by a limited
      brain distribution. Glucosylation is an effective way to enhance the brain
      targeting ability of drugs, but the bidirectional transport of glucose
      transporter 1 (GLUT1 ) might decrease the concentrations of venlafaxine-glucose
      (V-G) in brain before the release of parent drug venlafaxine. To conquer this
      drawback of GLUT1 , "lock-in" thiamine disulfide system (TDS) was introduced to
      modify the V-G conjugate. Both conjugates could release venlafaxine when
      incubated with the various buffers, mice plasma, and brain homogenate. The
      evaluation in vivo demonstrated that venlafaxine-TDS-glucose (V-TDS-G) had an
      improved targeting ability and significantly increased the level of venlafaxine
      in brain compared to the naked venlafaxine and V-G. The relative uptake
      efficiency (RE) and concentration efficiency (CE) were enhanced to 5.69 and 5.70
      times higher than that of naked venlafaxine, respectively. The results of this
      study suggest that the conjugate strategy based on the glucose-TDS (G-TDS) is
      available to enhance the delivery of central nervous system (CNS) drugs into
      brain.

PMID- 29063719
TI  - Aberrant single-minded homolog 1 methylation as a potential biomarker for
      cervical cancer.
AB  - BACKGROUND: The aim of this study is to evaluate the possibility of using the
      methylation status of single-minded homolog 1 (SIM1) as a diagnostic biomarker
      for cervical cancer. METHODS: All the patient and normal specimens including the
      normal cervix (n = 10), cervical cancer tissues (n = 45), blood (n = 45), and
      cervical brush specimens (n = 110) were retrospectively obtained. Quantitative
      methylation-specific PCR was performed to detect SIM1 methylation in primary
      tumors, cervical brush specimens, and plasma circulating cell-free DNA (ccfDNA).
      SIM1 expression was detected by western blot analysis. RESULTS: We found that
      SIM1 was highly methylated in the majority of the cervical cancer tissues that we
      tested, but not in any of the normal tissues. Hypermethylation of SIM1 led to a
      pronounced reduction in SIM1 expression in cervical cancer tissues compared with
      normal cervix. SIM1 methylation status on cervical brush specimens also
      distinguished cervical cancer from normal, cervical intraepithelial neoplasia
      (CIN) 1 and 2. The degree of SIM1 methylation was significantly associated with
      the severity of the disease (Ptrend  < .0001). We also investigated the
      possibility of detecting methylated SIM1 in plasma ccfDNA from cervical cancer
      patients. Methylated SIM1 was detected in 36.6% (15/41) of ccfDNA samples, and
      concordance rate with the matched cancer tissues was 41.5% (17/41) with
      sensitivity 38.5% and specificity 100%. CONCLUSION: This study has shown that
      SIM1 is frequently hypermethylated in cervical cancer, compared with normal
      cervix tissue, CIN1 and 2 samples, suggesting that the methylation status of SIM1
      could be a potential diagnostic biomarker for cervical cancer.

PMID- 29063720
TI  - Association of CDKN2A/CDKN2B with inflammatory bowel disease in Koreans.
AB  - BACKGROUND AND AIM: CDKN2A/CDKN2B locus on 9p21 is reported to be associated with
      various diseases, including cancer and cardiovascular and inflammatory diseases.
      Significant downregulation of CDKN2B-AS1 in inflamed colon tissue of inflammatory
      bowel disease (IBD) cases was reported in Europeans. This study aimed to confirm
      the suggestive association of CDKN2A/CDKN2B with IBD identified in our recent
      genome-wide association study (GWAS). METHODS: We examined the association of
      CDKN2A/CDKN2B locus with IBD in an additional sample of 574 IBD cases and 542
      controls, totaling 4068 cases and 8074 controls. In silico study was performed at
      various levels for functional annotation of the causal variant. Co-localization
      of the GWAS association signals and the corresponding expression quantitative
      trait loci in IBD-related tissues was evaluated using eCAVIAR. RESULTS: An
      expanded GWAS showed genome-wide significant association of rs3731257 at 9p21
      with IBD (odds ratio = 1.17, 95% confidence interval = 1.12-1.22, Pcombined  =
      5.68 * 10-9 ) and Crohn's disease (odds ratio = 1.22, 95% confidence interval =
      1.15-1.28, Pcombined  = 8.85 * 10-9 ) in the Korean population. Co-localization
      study suggested that both CDKN2B-AS1 and CDKN2A might be functionally associated
      with the locus in the small intestine. CONCLUSIONS: rs3731257 in CDKN2A/CDKN2B is
      an IBD-susceptible locus in Koreans, with a suggestive role for small intestine
      specific gene regulation. Our findings suggested that alterations of the
      CDKN2A/CDKN2B locus could affect the pathophysiology of IBD.

PMID- 29063721
TI  - High yield purification and first structural characterization of the full-length
      bacterial toxin CNF1.
AB  - The Cytotoxic Necrotizing Factor 1 (CNF1) is a bacterial toxin secreted by
      certain Escherichia coli strains causing severe pathologies, making it a protein
      of pivotal interest in toxicology. In parallel, the CNF1 capability to influence
      important neuronal processes, like neuronal arborization, astrocytic support, and
      efficient ATP production, has been efficiently used in the treatment of
      neurological diseases, making it a promising candidate for therapy. Nonetheless,
      there are still some unsolved issues about the CNF1 mechanism of action and
      structuration probably caused by the difficulty to achieve sufficient amounts of
      the full-length protein for further studies. Here, we propose an efficient
      strategy for the production and purification of this toxin as a his-tagged
      recombinant protein from E. coli extracts (CNF1-H8). CNF1-H8 was expressed at the
      low temperature of 15 degrees C to diminish its characteristic degradation. Then,
      its purification was achieved using an immobilized metal affinity chromatography
      (IMAC) and a size exclusion chromatography so as to collect up to 8 mg of protein
      per liter of culture in a highly pure form. Routine dynamic light scattering
      (DLS) experiments showed that the recombinant protein preparations were
      homogeneous and preserved this state for a long time. Furthermore, CNF1-H8
      functionality was confirmed by testing its activity on purified RhoA and on HEp-2
      cultured cells. Finally, a first structural characterization of the full-length
      toxin in terms of secondary structure and thermal stability was performed by
      circular dichroism (CD). These studies demonstrate that our system can be used to
      produce high quantities of pure recombinant protein for a detailed structural
      analysis. (c) 2017 American Institute of Chemical Engineers Biotechnol. Prog.,
      34:150-159, 2018.

PMID- 29063722
TI  - A quality improvement initiative to increase the safety of pediatric emergency
      airway management.
AB  - BACKGROUND: Emergency airway management is commonly associated with life
      threatening hypoxia and hypotension which may be preventable. AIMS: The aim of
      this quality improvement study was to reduce the frequency of intubation-related
      hypoxia and hypotension. METHODS: This prospective quality improvement study was
      conducted over 4 years in the Emergency Department of The Royal Children's
      Hospital, Melbourne, Australia. A preintervention cohort highlighted safety gaps
      and was used to design study interventions, including an emergency airway
      algorithm, standardized airway equipment, a preintubation checklist and equipment
      template, endtidal carbon dioxide monitoring, postintubation team debriefing, and
      multidisciplinary team training. Following implementation, a postintervention
      cohort was used to monitor the impact of study interventions on clinical process
      and patient outcome. Process measures were as follows: use of a preintubation
      checklist, verbalization of an airway plan, adequate resuscitation prior to
      intubation, induction agent dose titration, use of apneic oxygenation, and use of
      endtidal carbon dioxide to confirm endotracheal tube position. The primary
      outcome measure was first pass success rate without hypoxia or hypotension.
      Potential harms from study interventions were monitored. RESULTS: Forty-six
      intubations were included over one calendar year in the postintervention cohort
      (compared to 71 in the preintervention cohort). Overall clinical uptake of the 6
      processes measures was 85%. First pass success rate without hypoxia or
      hypotension was 78% in the postintervention cohort compared with 49% in the
      preintervention cohort (absolute risk reduction: 29.0%; 95% confidence interval
      12.3%-45.6%, number needed to treat: 3.5). No significant harms from study
      interventions were identified. CONCLUSION: Quality improvement initiatives
      targeting emergency airway management may be successfully implemented in the
      emergency department and are associated with a reduction in adverse intubation
      related events.

PMID- 29063723
TI  - Revealing Conformational Variants of Solution-Phase Intrinsically Disordered Tau
      Protein at the Single-Molecule Level.
AB  - Intrinsically disordered proteins, such as tau protein, adopt a variety of
      conformations in solution, complicating solution-phase structural studies. We
      employed an anti-Brownian electrokinetic (ABEL) trap to prolong measurements of
      single tau proteins in solution. Once trapped, we recorded the fluorescence
      anisotropy to investigate the diversity of conformations sampled by the single
      molecules. A distribution of anisotropy values obtained from trapped tau protein
      is conspicuously bimodal while those obtained by trapping a globular protein or
      individual fluorophores are not. Time-resolved fluorescence anisotropy
      measurements were used to provide an explanation of the bimodal distribution as
      originating from a shift in the compaction of the two different families of
      conformations.

PMID- 29063725
TI  - Associations of specific postoperative complications with costs after radical
      cystectomy.
AB  - OBJECTIVE: To quantify the financial impact of complications after radical
      cystectomy (RC) and their associations with respective 90-day costs, as RC is a
      morbid surgery plagued by complications and the expenditure attributed to
      specific complications after RC is not well characterised. PATIENTS AND METHODS:
      We used the Premier Hospital Database (Premier Inc., Charlotte, NC, USA) to
      identify 9 137 RC patients (weighted population of 57 553) from 360 hospitals
      between 2003 and 2013. Complications were categorised according to Agency for
      Healthcare Research and Quality Clinical Classifications. Patients with and
      without complications were compared, and multivariable analysis was performed.
      RESULTS: An index complication increased costs by $9 262 (95% confidence interval
      [CI] 8 300-10 223) and a readmission complication increased costs by $20 697 (95%
      CI 18 735-22 660). The four most costly index complications (descending order)
      were venous thromboembolism (VTE), infection, wound and soft tissue
      complications, and pulmonary complications (P < 0.001, vs no complication). A
      complication increased length of stay by 4 days (95% CI 3.6-4.3). One in five
      patients were readmitted in 90 days and the four costliest readmission
      complications (descending order) were pulmonary, bleeding, VTE, and
      gastrointestinal complications (P < 0.001, vs no complication). Readmitted
      patients had multiple complications upon readmission (median of 3, interquartile
      range 2-4). On multivariable analysis, more comorbidities, longer surgery (>6 h),
      transfusions of >3 units, and teaching hospitals were associated with higher
      costs (P < 0.05), whilst high-volume surgeons and shorter surgeries (<4 h) were
      associated with lower costs (P < 0.05). CONCLUSIONS: Complications after RC
      increase index and readmission costs for hospitals, and can be categorised based
      on magnitude. Future initiatives in RC may also consider costs of complications
      when establishing quality improvement priorities for patients, providers, or
      policymakers.

PMID- 29063724
TI  - Prevalence of rear seat belt use among pregnant women in a suburban area of
      Japan.
AB  - AIM: The aim of this study was to clarify the prevalence and influencing factors
      of rear seat belt use among pregnant women. METHODS: Questionnaires were given to
      1546 pregnant women who visited obstetrics clinics and hospitals for prenatal
      checkups from October to December 2013. A total of 1494 pregnant women (96.6%)
      agreed to participate in this study and completed the questionnaire. RESULTS:
      Fewer than 20% of the rear-seat passengers 'always' used seat belts before and
      during pregnancy, whereas a third 'never' used a seat belt before or during
      pregnancy. There was no significant decrease in seat belt use by rear-seat
      passengers during compared to before pregnancy. Multivariate analysis revealed
      that age, knowledge of how to use a seat belt during pregnancy, belief in the
      compulsory use of a rear seat belt and driver behavioral characteristics before
      pregnancy were associated with rear seat belt use during pregnancy. CONCLUSIONS:
      The prevalence of fastening seat belts was substantially low. The provision of
      information regarding proper seat belt use and its role in protecting the fetus
      may increase use.

PMID- 29063726
TI  - Phenological match drives pollen-mediated gene flow in a temporally dimorphic
      tree.
AB  - Variation in flowering phenology is common in natural populations, and is
      expected to be, together with inter-mate distance, an important driver of
      effective pollen dispersal. In populations composed of plants with temporally
      separated sexual phases (i.e. dichogamous or heterodichogamous populations),
      pollen-mediated gene flow is assumed to reflect phenological overlap between
      complementary sexual phases. In this study, we conducted paternity analyses to
      test this hypothesis in the temporally dimorphic tree Acer opalus. We performed
      spatially explicit analyses based on categorical and fractional paternity
      assignment, and included tree size, pair-wise genetic relatedness and morph type
      as additional predictors. Because differences between morphs in flowering
      phenology may also influence pollination distances, we modelled separate pollen
      dispersal kernels for the two morphs. Extended phenological overlap between male
      and female phases (mainly associated with inter-morph crosses) resulted in higher
      siring success after accounting for the effects of genetic relatedness, morph
      type and tree size, while reduced phenological overlap (mainly associated with
      intra-morph crosses) resulted in longer pollination distances achieved. Siring
      success also increased in larger trees. Mating patterns could not be predicted by
      phenology alone. However, as heterogeneity in flowering phenology was the single
      morph-specific predictor of siring success, it is expected to be key in
      maintaining the temporal dimorphism in A. opalus, by promoting not only a
      prevalent pattern of inter-morph mating, but also long-distance pollination
      resulting from intra-morph mating events.

PMID- 29063727
TI  - Nurse-driven analgesia and sedation in pediatric patients with univentricular
      hearts requiring extracorporeal life support after first-stage palliation
      surgery: A pilot study.
AB  - BACKGROUND: Few data are available regarding requirements of sedation and
      analgesia in children during extracorporeal life support. AIMS: The aim of this
      study was to evaluate if children with functionally univentricular hearts on
      extracorporeal life support after first-stage palliation surgery have higher
      requirement of analgesics and sedatives compared with children without
      extracorporeal life support using a goal-directed nurse-driven analgesia and
      sedation protocol. METHODS: This prospective observational matched case-control
      pilot study was conducted at a cardiac pediatric intensive care unit of a
      tertiary referral center. Seventeen patients with functionally univentricular
      hearts including hypoplastic left heart syndrome who were on extracorporeal life
      support after first-stage palliation surgery were enrolled from July 2012 to
      January 2017. Seventeen matched patients served as controls. Doses of morphine,
      midazolam, clonidine, and muscle relaxants as well as sedation scores (COMFORT
      behavior scale and the nurse interpretation of sedation scale) were assessed
      according to a nurse-driven protocol every 8 hours up to 120 hours after first
      stage palliation surgery. RESULTS: Sedation scores were equal in the
      extracorporeal life support group and in the control group at most points in
      time. There was no significant difference in cumulative doses of morphine and
      midazolam. However, children of the extracorporeal life support group received
      higher doses of midazolam and morphine at some points in time. CONCLUSION: A
      nurse-driven protocol for analgesia and sedation of children with extracorporeal
      life support is feasible. Patients with extracorporeal life support do not need
      deeper sedation levels and have not higher cumulative sedation requirements than
      children without extracorporeal life support.

PMID- 29063728
TI  - Laparoscopic and robot-assisted vs open radical prostatectomy for the treatment
      of localized prostate cancer: a Cochrane systematic review.
AB  - OBJECTIVE: To determine the effects of laparoscopic radical prostatectomy (LRP),
      or robot-assisted radical prostatectomy (RARP) compared with open radical
      prostatectomy (ORP) in men with localized prostate cancer. MATERIALS AND METHODS:
      We performed a comprehensive search using multiple databases (CENTRAL, MEDLINE,
      EMBASE) and abstract proceedings, with no restrictions on the language of
      publication or publication status, up until 9 June 2017. We included all
      randomized or pseudo-randomized controlled trials that directly compared LRP and
      RARP with ORP. Two review authors independently examined full-text reports,
      identified relevant studies, assessed the eligibility of studies for inclusion,
      extracted data and assessed risk of bias. We performed statistical analyses using
      a random-effects model and assessed the quality of the evidence according to
      Grading of Recommendations Assessment, Development and Evaluation (GRADE). The
      primary outcomes were prostate cancer-specific survival, urinary quality of life
      and sexual quality of life. Secondary outcomes were biochemical recurrence-free
      survival, overall survival, overall surgical complications, serious postoperative
      surgical complications, postoperative pain, hospital stay and blood transfusions.
      RESULTS: We included two unique studies in a total of 446 randomized participants
      with clinically localized prostate cancer. All available outcome data were short
      term (up to 3 months). We found no study that addressed the outcome of prostate
      cancer-specific survival. Based on one trial, RARP probably results in little to
      no difference in urinary quality of life (mean difference [MD] -1.30, 95%
      confidence interval [CI] -4.65 to 2.05; moderate quality of evidence) and sexual
      quality of life (MD 3.90, 95% CI: -1.84 to 9.64; moderate quality of evidence).
      No study addressed the outcomes of biochemical recurrence-free survival or
      overall survival. Based on one trial, RARP may result in little to no difference
      in overall surgical complications (risk ratio [RR] 0.41, 95% CI: 0.16-1.04; low
      quality of evidence) or serious postoperative complications (RR 0.16, 95% CI:
      0.02-1.32; low quality of evidence). Based on two studies, LRP or RARP may result
      in a small, possibly unimportant improvement in postoperative pain at 1 day (MD 
      1.05, 95% CI: -1.42 to -0.68; low quality of evidence) and up to 1 week (MD 
      0.78, 95% CI: -1.40 to -0.17; low quality of evidence). Based on one study, RARP
      probably results in little to no difference in postoperative pain at 12 weeks (MD
      0.01, 95% CI: -0.32 to 0.34; moderate quality of evidence). Based on one study,
      RARP probably reduces the length of hospital stay (MD -1.72, 95% CI: -2.19 to 
      1.25; moderate quality of evidence). Based on two studies, LRP or RARP may reduce
      the frequency of blood transfusions (RR 0.24, 95% CI: 0.12-0.46; low quality of
      evidence). Assuming a baseline risk for a blood transfusion to be 8.9%, LRP or
      RARP would result in 68 fewer blood transfusions per 1,000 men (95% CI: 78-48
      fewer). CONCLUSIONS: There is no evidence to inform the comparative effectiveness
      of LRP or RARP compared with ORP for oncological outcomes. Urinary and sexual
      quality of life appear similar. Overall and serious postoperative complication
      rates appear similar. The difference in postoperative pain may be minimal. Men
      undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood
      transfusions.

PMID- 29063729
TI  - Dual Mechanism of an Intramolecular Charge Transfer (ICT)-FRET-Based Fluorescent
      Probe for the Selective Detection of Hydrogen Peroxide.
AB  - A dual-mechanism intramolecular charge transfer (ICT)-FRET fluorescent probe for
      the selective detection of H2 O2 in living cells has been designed and
      synthesized. This probe used a coumarin-naphthalimide hybrid as the FRET platform
      and a boronate moiety as the recognition group. Upon the addition of H2 O2 , the
      probe exhibited a redshifted (73 nm) fluorescence emission, and the ratio of
      fluorescence intensities at lambda=558 and 485 nm (F558 /F485 ) shifted notably
      (up to 100-fold). Moreover, there was a good linearity (R2 =0.9911) between the
      ratio and concentration of H2 O2 in the range of 0 to 60 MUm, with a limit of
      detection of 0.28 MUm (signal to noise ratio (S/N)=3). This probe could also
      detect enzymatically generated H2 O2 . Importantly, it could be used to visualize
      endogenous H2 O2 produced by stimulation from epidermal growth factor.

PMID- 29063731
TI  - Exhaustive sampling of the fragment space associated to a molecule leading to the
      generation of conserved fragments.
AB  - The first step in hit optimization is the identification of the pharmacophore,
      which is normally achieved by deconstruction of the hit molecule to generate
      "deletion analogues." In silico fragmentation approaches often focus on the
      generation of small fragments that do not describe properly the fragment space
      associated to the deletion analogues. We present significant modifications to the
      molecular fragmentation programme molBLOCKS, which allows the exhaustive sampling
      of the fragment space associated with a molecule to generate all possible
      molecular fragments. This generates larger fragments, by combining the smallest
      fragments. Additionally, it has been modified to deal with the problem of
      changing pharmacophoric properties through fragmentation, by highlighting bond
      cuts. The modified molBLOCKS programme was used on a set of drug compounds, where
      it generated more unique fragments than standard fragmentation approaches by
      increasing the number of fragments derived per compound. This fragment set was
      found to be more diverse than those generated by standard fragmentation
      programmes and was relevant to drug discovery as it contains the key fragments
      representing the pharmacophoric elements associated with ligand recognition. The
      use of dummy atoms to highlight bond cuts further increases the information
      content of fragments by visualizing their previous bonding pattern.

PMID- 29063732
TI  - Timing, intensity, and duration of household food insecurity are associated with
      early childhood development in Kenya.
AB  - This study examines the association between 3 dimensions of food insecurity
      (timing, intensity, and duration) and 3 domains of child development (gross
      motor, communication, and personal social). Longitudinal data from 303 households
      (n = 309 children) visited 9 times over 2 years were collected. Children in
      households experiencing severe food insecurity 3 months prior (timing) had
      significantly lower gross motor (beta -0.14; 95% CI [0.27, -0.0033]; p = .045),
      communication (beta -0.16; 95% CI [-0.30, -0.023]; p = .023), and personal social
      (beta -0.20; 95% CI [-0.33, -0.073]; p = .002) Z-scores, using lagged
      longitudinal linear models controlling for current food insecurity; these results
      were attenuated in full models, which included maternal education, household
      asset index, and child anthropometry. Children in households that experienced
      greater aggregate food insecurity over the past 2 years (intensity) had
      significantly lower gross motor (beta -0.047; 95% CI [-0.077, -0.018]; p = .002),
      communication (beta -0.042; 95% CI [-0.076, -0.0073]; p = .018), and personal
      social (beta -0.042; 95% CI [-0.074, -0.010]; p = .010) Z-scores; these results
      were also attenuated in full models. Children with more time exposed to food
      insecurity (duration) had significantly lower gross motor (beta -0.050; 95% CI [
      0.087, -0.012]; p = .010), communication (beta -0.042; 95% CI [-0.086, 0.0013]; p
      = .057), and personal social (beta -0.037; 95% CI [-0.077, 0.0039]; p = .076) Z
      scores; these results were no longer significant in full models. Our findings
      suggest that acute and chronic food insecurity and child development are related,
      but that many associations are attenuated with the inclusion of relevant
      covariates.

PMID- 29063733
TI  - Design and synthesis of 9H-fluorenone based 1,2,3-triazole analogues as
      Mycobacterium tuberculosis InhA inhibitors.
AB  - We prepared fifty various 9H-fluorenone based 1,2,3-triazole analogues varied
      with NH, -S-, and -SO2 - groups using click chemistry. The target compounds were
      characterized by routine analytical techniques, 1 H, 13 CNMR, mass, elemental,
      single-crystal XRD (8a) and screened for in vitro antitubercular activity against
      Mycobacterium tuberculosis (MTB) H37Rv strain and two "wild" strains Spec. 210
      and Spec. 192 and MIC50 was determined. Further, the compounds were evaluated for
      MTB InhA inhibition study as well. The final analogues exhibited minimum
      inhibitory concentration (MIC) ranging from 52.35 to >295 MUm. Among the -NH-
      analogues, one compound 5p (MIC 58.34 MUm), among -S- containing analogues four
      compounds 8e (MIC 66.94 MUm), 8f (MIC 74.20 MUm), 8g (MIC 57.55 MUm), and 8q (MIC
      56.11 MUm), among -SO2 - containing compounds one compound 10p (MIC 52.35 MUm)
      showed less than MTB MIC 74.20 MUm: Compound 4-(((9H-fluoren-9
      yl)sulfonyl)methyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole (10p) was found
      to be the most active compound with 73% InhA inhibition at 50 MUm; it inhibited
      MTB with MIC 52.35 MUm. Further, 10f and 10p were docked to crystal structure of
      InhA to know binding interaction pattern. Most active compounds were found to be
      non-cytotoxic against HEK 293 cell lines at 50 MUm.

PMID- 29063730
TI  - Fibroblast growth factors in the management of spinal cord injury.
AB  - Spinal cord injury (SCI) possesses a significant health and economic burden
      worldwide. Traumatic SCI is a devastating condition that evolves through two
      successive stages. Throughout each of these stages, disturbances in ionic
      homeostasis, local oedema, ischaemia, focal haemorrhage, free radicals stress and
      inflammatory response were observed. Although there are no fully restorative
      cures available for SCI patients, various molecular, cellular and rehabilitative
      therapies, such as limiting local inflammation, preventing secondary cell death
      and enhancing the plasticity of local circuits in the spinal cord, were
      described. Current preclinical studies have showed that fibroblast growth factors
      (FGFs) alone or combination therapies utilizing cell transplantation and
      biomaterial scaffolds are proven effective for treating SCI in animal models.
      More importantly, some studies further demonstrated a paucity of clinical
      transfer usage to promote functional recovery of numerous patients with SCI. In
      this review, we focus on the therapeutic capacity and pitfalls of the FGF family
      and its clinical application for treating SCI, including the signalling component
      of the FGF pathway and the role in the central nervous system, the
      pathophysiology of SCI and the targets for FGF treatment. We also discuss the
      challenges and potential for the clinical translation of FGF-based approaches
      into treatments for SCI.

PMID- 29063734
TI  - Identifying candidates for super-extended staging pelvic lymph node dissection
      among patients with high-risk prostate cancer.
AB  - OBJECTIVES: To assess if the preoperative lymph node invasion (LNI) risk could be
      used to tailor the extent of pelvic lymph node dissection (PLND) according to
      individual profile in patients with prostate cancer (PCa) undergoing radical
      prostatectomy (RP), and to identify those who would benefit from the removal of
      the common iliac and pre-sacral nodes. PATIENTS AND METHODS: A total of 471
      patients with high-risk PCa treated with RP and a super-extended PLND that
      included the removal of the pre-sacral and common iliac nodes between 2006 and
      2016 were identified. The risk of LNI was calculated according to the Briganti
      nomogram. Multivariable logistic regression analyses assessed the association
      between LNI risk and involvement of the common iliac and pre-sacral regions. The
      risk of positive common iliac and pre-sacral nodes was plotted over the LNI risk
      using the LOWESS-smoothed fit curve. RESULTS: The median preoperative LNI risk
      was 25.5%. The median number of nodes removed was 23, and 171 (36.3%) patients
      had LNI. Overall, 61 (13.0%) and 28 patients (5.9%), respectively, had positive
      common iliac and pre-sacral nodes alone or in combination with other sites. The
      LNI risk was associated with the involvement of the common iliac and pre-sacral
      regions (all P < 0.001). The proportion of patients with positive common iliac
      and pre-sacral nodes progressively increased according to the LNI risk. The
      adoption of a 30% threshold would result in avoiding the removal of the common
      iliac and pre-sacral nodes in >60% cases, with a risk of missing LNI in these
      regions of <5%. CONCLUSIONS: Fewer than 5% of patients with an LNI risk of <30%
      harbour positive common iliac and pre-sacral nodes. A super-extended PLND that
      includes the dissection of these regions should be considered exclusively in
      patients with an LNI risk >=30%.

PMID- 29063735
TI  - Remarkable response of nivolumab-refractory lung cancer to salvage chemotherapy.
AB  - Promising outcomes of salvage chemotherapy after nivolumab therapy have been
      reported; however, little is known about the detailed clinical and immunologic
      features in lung cancer patients in whom nivolumab is unsuccessful. We report two
      cases of nivolumab-refractory lung cancer, in which chemotherapy resulted in
      rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens
      showed PD-ligand 1 (PD-L1)-expressing cancer cells, accompanied by tumor
      infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive
      regulatory T cells and cells positive for TIM-3 were also observed. Physicians
      should take caution in treating lung cancer patients after progression on
      nivolumab. Further studies with a large cohort are warranted to identify the
      patients that may benefit from salvage chemotherapy.

PMID- 29063736
TI  - A practical guide to the preparation and use of metal ion-buffered systems for
      physiological research.
AB  - Recent recognition that mobile pools of Zn2+ and Cu2+ are involved in the
      regulation of neuronal, endocrine and other cells has stimulated the development
      of tools to visualize and quantify the level of free trace metal ions. Most of
      the methods used to measure or control loosely bound metals require reference
      media that contain exactly defined free concentrations of the target ions.
      Despite the central importance of proper metal ion buffering, there is still a
      lack of international standards and beginners in the field may have difficulties
      finding a coherent description of how to prepare trace metal ion buffers,
      especially when experiments are to be performed in multimetal systems. To close
      this gap, we provide a guide for the design, preparation and use of metal ion
      buffered systems that facilitate immediate application under physiologically
      relevant ionic conditions. Thermodynamic and kinetic concepts of chemical
      speciation as well as general protocols and specific examples are outlined for
      the accurate preparation of single- and dual-metal ion buffers. In addition,
      experiments have been performed with FluoZin-3 to illustrate that metal ion
      buffered systems are required for reliable preparation of nanomolar Zn2+
      solutions and that dual-metal ion buffers can be used to calibrate suitable
      fluorescent Zn2+ sensors in the presence of millimolar Ca2+ concentrations.
      Together, the information provided should sensitize readers to the many potential
      pitfalls and uncertainties that exist when working with physiologically relevant
      concentrations of trace metal ions and enable them to formulate their own metal
      ion buffers for most in vitro applications.

PMID- 29063738
TI  - Cardiovascular outcomes of pregnancy in Marfan's syndrome patients: A literature
      review.
AB  - AIMS: Pregnancy in patients with Marfan's syndrome (MFS) carries an increased
      risk of cardiovascular complications, resulting in increased maternal and fetal
      mortality and morbidity. Literature on MFS pregnant patients is relatively
      sparse, and there has yet to be a concrete consensus on the management of this
      unique patient population. The purpose of our paper is to provide a literature
      review of case reports and studies on MFS during pregnancy (published between
      2005 and 2015) and to explore cardiovascular outcomes of patients with MFS.
      METHODS AND RESULTS: Of the 852 women in our review, there were 1112 pregnancies,
      with an aortic dissection rate of 7.9% and mortality of 1.2%. Data demonstrated a
      trend that patients whose aortic diameter >=40 mm had a greater rate of
      dissection than MFS patients whose aortic diameter <40 mm (Fisher's exact test, P
      = .0504). Fetal outcome included a 5.6% mortality rate and 41% of births were
      cesarean deliveries and of those reported, 75% secondary to cardiac emergencies.
      CONCLUSIONS: Patients with MFS, especially those whose initial aortic diameters
      >=40 mm, planning a pregnancy or currently pregnant should be carefully counseled
      about the maternal and fetal risks throughout pregnancy. MFS patients whose
      aortic diameters >=40 mm should be advised to ideally await pregnancy until
      prophylactic aortic surgery. As MFS varies in its phenotypic expression, each
      patient's risk of adverse cardiac events should be assessed individually through
      a joint Maternal Fetal Medicine and Cardiology Center.

PMID- 29063739
TI  - Microbial Biotechnology is 10!

PMID- 29063737
TI  - Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb
      Wounds in Horses.
AB  - Distal extremity wounds are a significant clinical problem in horses and humans
      and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated
      the effects of direct wound treatment with allogeneic stem cells, in terms of
      gross, histologic, and transcriptional features of healing. Three full-thickness
      cutaneous wounds were created on each distal forelimb in six healthy horses, for
      a total of six wounds per horse. Umbilical cord-blood derived equine MSCs were
      applied to each wound 1 day after wound creation, in one of four forms: (a)
      normoxic- or (b) hypoxic-preconditioned cells injected into wound margins, or (c)
      normoxic- or (d) hypoxic-preconditioned cells embedded in an autologous fibrin
      gel and applied topically to the wound bed. Controls were one blank (saline)
      injected wound and one blank fibrin gel-treated wound per horse. Data were
      collected weekly for 6 weeks and included wound surface area, thermography, gene
      expression, and histologic scoring. Results indicated that MSC treatment by
      either delivery method was safe and improved histologic outcomes and wound area.
      Hypoxic-preconditioning did not offer an advantage. MSC treatment by injection
      resulted in statistically significant increases in transforming growth factor
      beta and cyclooxygenase-2 expression at week 1. Histologically, significantly
      more MSC-treated wounds were categorized as pro-healing than pro-inflammatory.
      Wound area was significantly affected by treatment: MSC-injected wounds were
      consistently smaller than gel-treated or control wounds. In conclusion, MSC
      therapy shows promise for distal extremity wounds in horses, particularly when
      applied by direct injection into the wound margin. Stem Cells Translational
      Medicine 2018;7:98-108.

PMID- 29063740
TI  - Submacular Hemorrhage: Visual Outcomes and Prognostic Factors.
AB  - PURPOSE: To describe causes, visual outcomes, and prognostic factors in patients
      with submacular hemorrhage (SMH). DESIGN: Retrospective case review. METHODS: We
      performed a retrospective review of SMH with a size of at least 1 disc diameter.
      SMH causes were classified into 3 groups: 1) neovascular age-related macular
      degeneration (nAMD), 2) polypoidal choroidal vasculopathy (PCV), and 3) other
      miscellaneous causes. RESULTS: Ninety-eight eyes of 98 patients were included.
      Based on clinical presentation and indocyanine green angiography (ICGA), the
      diagnoses of PCV (59%), nAMD (31%), and miscellaneous other causes (10%) were
      made. PCV patients were younger (P = 0.005) and had larger SMH size than nAMD
      patients (P = 0.008). Poor visual outcome [>1.0 logarithm of the minimum angle of
      resolution (logMAR)] at 6 months was associated with low initial visual acuity
      (VA; >1.0 logMAR; P = 0.002) and with the diagnosis of nAMD (P = 0.02). In
      addition, limited visual outcomes were noted for patients older than 65 years and
      those with persistent SMH for at least 2 months. CONCLUSIONS: PCV was the most
      common cause of SMH in Thailand. ICGA represented a valuable tool for the
      diagnosis. Visual outcomes were limited for patients with nAMD and for patients
      who presented with poor initial VA.

PMID- 29063742
TI  - Corrigenda: Omission of the Description of Informed Consent on the Identifiable
      Photos and the Description on Ethical Treatment of Experimental Animals.

PMID- 29063741
TI  - Optic Nerve Head Hemorrhages Associated With Posterior Vitreous Detachment.
AB  - PURPOSE: To report and evaluate the clinical and optical coherence tomography
      (OCT) features of optic nerve hemorrhages (ONH) associated with spontaneous
      posterior vitreous detachment (PVD). DESIGN: A prospective case series conducted
      at a private ophthalmic practice in Auckland, New Zealand. METHODS: A consecutive
      series of patients presenting at a private multispecialty practice in Auckland,
      New Zealand, with symptoms of PVD with ONH underwent imaging of the optic nerve
      with digital retinal photography and OCT. The number and location of each
      hemorrhage were recorded, together with relevant ophthalmic and demographic data.
      RESULTS: Twenty of 30 eyes with ONH had evidence of persistent vitreopapillary
      adhesion. Three patterns of adhesion were identified: central, peripheral, and
      combined. In all, 52 hemorrhages were identified, of which the majority were
      flame-shaped, although other types were seen including dot and blot hemorrhages.
      One subretinal hemorrhage occurred in a patient with a central vitreopapillary
      adhesion. CONCLUSIONS: ONH hemorrhages associated with PVD are commonly found
      with persistent vitreopapillary adhesions as evidenced on OCT. The clinical
      features of ONH together with OCT imaging may help to distinguish ONH associated
      with PVD from other hemorrhages found on or adjacent to the optic nerve.

PMID- 29063743
TI  - Transorbital superior eyelid endoscopic approach to the temporal lobe.

PMID- 29063744
TI  - Tailored surgical strategy in clival chordomas: an extraordinary selection bias
      that limits approach comparison.

PMID- 29063745
TI  - Neurosurgery and neuroethics.

PMID- 29063746
TI  - Ogilvie's syndrome following spinal surgery.

PMID- 29063747
TI  - Pregnancy outcomes in women with endometriosis.
AB  - BACKGROUND: The aim of this study was to investigate whether patients with
      endometriosis who achieved pregnancy have a higher risk for pregnancy
      complications and adverse perinatal outcomes as compared to patients without
      endometriosis. METHODS: The study compared obstetrical and perinatal outcomes of
      women with and without endometriosis who delivered between 1988-2013 at the
      Soroka University Medical Center. The study population included 504 deliveries
      divided into the following groups: 1) women with endometriosis (N.=35); and 2)
      without endometriosis (N.=467). Endometriosis was diagnosed by laparoscopy or
      laparotomy. Multiple logistic regression models were used to control for
      confounders. RESULTS: No significant increase in obstetrical complications was
      noted in the endometriosis group, but significantly higher rates of cesarean
      sections. Perinatal outcomes were comparable between the groups. CONCLUSIONS: In
      our population, endometriosis was not found as a risk factor for obstetrical
      complications or adverse perinatal outcomes. Larger population based cohort
      studies are needed to clarify the relationship between endometriosis and adverse
      pregnancy outcomes.

PMID- 29063748
TI  - New data on chronic venous disease: a new place for Cyclo 3(r) Fort.
AB  - With our increasing knowledge of the epidemiology, pathophysiology, investigation
      and clinical aspects of chronic venous disease (CVD) and new data on the various
      therapies available, an update of the recommendations on CVD and its management
      appears to be necessary. The symposium New Data on Chronic Venous Disease: A New
      Place for Cyclo 3(r) Fort, held during the annual meeting of the European Venous
      Forum on June 30th, 2017 in Porto, Portugal, reported the recent developments on
      the Ruscus, hesperidin methyl chalcone (HMC), and vitamin C combination (Cyclo
      3(r) Fort), including the results of a series of in-vivo pharmacological
      experiments and a recent meta-analysis. Additionally, the symposium provided
      first-hand information on the process, rules, main findings, and expected
      contents of the prospective 2018 CVD guidelines. Analysis of the evidence showed
      that the effect of the Ruscus, HMC, and vitamin C combination on pain, heaviness,
      feeling of swelling, tingling, ankle circumference and global symptoms score
      reached Grade A. Therefore, the new guidelines should specify that the Ruscus,
      HMC, and vitamin C combination merits a Grade 1A recommendation.

PMID- 29063749
TI  - [RECONSTRUCTING THE LIFE OF AN UNKNOWN MAN--INTERDISCIPLINARY APPROACH].
AB  - The remains of a tomb were discovered below the foundations of the Roman church
      of "Majka Bozja Gorska" in Lobor in2002. It was a vaulted tomb carved from a
      single stone. The narthex of ancient Christian and pre-roman churches oftenserved
      as the resting place of religious, secular and noble dignitaries, who were
      credited for founding the church at thetime. By anthropological methods, the age,
      gender, height, pathological changes, tendon and ligament hinges and degreeof
      development were able to be analysed. The stable isotopes of Carbon-13, Nitrogen
      15 and Oxygen-18 were analysedand expressed as ??-values according to the PDB
      standard. Dental analysis showed a build-up of tartar on the buccal side,with 5
      teeth missing from the dentition post-mortem and a partial lowering and accretion
      of the alveolar walls of the 2ndmolar space secondary to tooth loss. The remains
      of the person from grave 107 show that the person was approximately30-35 years of
      age, confirmed by microscopical analysis of the bone samples. Almost all of the
      cranial sutures wereexposed with the exception of the saggital suture which was
      closed at the S3 position, while the transverse palatal suturewas in the initial
      stages of closure on the lateral sides. Analysis of the iliac bone showed visible
      changes on the bone. Thesurface had retained its youthful appearance however with
      a microporous and pronounced granular structure and onlya slight apical and
      marginal activity. The transverse striations are still apparent, but no longer
      along the entirety of thebone surface. Anthropometric analysis according to
      cranial cavity indexes, showed a cranium or relatively large
      volume(aristencephalic in type), long, narrow and medium in height. The index
      values were used in facial reconstruction. Analysisof the development of tendon
      and ligament hinges of the preserved anatomical elements, gave further
      information aboutthe morphology and physical activity of the person. The hinge
      sites of the brachial and antebrachial muscles showed asignificant development
      and these enthesopathies would be consistent with a strenuous physical activity,
      especially at thebiceps tendon and shoulder girdle, portraying an anterior
      elevation, cubital flexion, pronation, circumduction and fixation. Itcan be said
      that the person predominantly used the left arm. The developed muscle hinges,
      show common pronatory andsupinatory movements and presume a routine swinging
      motion of an object above the head or in front of the person. Theleft tibia was
      suggestive of the height and male gender of the person. According to Pearson's
      regression formula, for thelength of the brachium, radius and tibia, it can be
      reasoned that the person was approximately 169 cm tall. The upper thirdof the L3
      vertebra shows a Schmorl's hernia which can be secondary to strong
      anteroposterior and lateral flexion of thespine. On the supero-lateral surface of
      the left patella, there is a Messeri sign, suggestive of a long and repeated
      flexion ofthe knee (kneeling). The molars of the lower and especially upper jaw
      show signs of paradontosis and a slight abrasion ofthe first degree according to
      Gustafson. The secondary dentin can be seen on the incisors, canines and molars.
      The boneimpression of the left temporal bone, was oval in shape and measured 12x9
      mm. It was probably and old, healed wound,possibly consequential to a fall or
      strike from a sharp object. The left tibia, showed a treated but still active
      periostitis.Analysis of the stable isotopes (C, N, O) shows an increased
      consumption of vegetables, common to a moderately warmand dry climate (millet).
      The person had access to water of a good quality, possibly from a well and did
      not eat fish or drinkwine. We do not know whether the person from grave 107 was a
      member of the clergy or nobility, but was most likely amember of the social
      elite.

PMID- 29063750
TI  - SERS-Fluorescence Dual-Mode pH-Sensing Method Based on Janus Microparticles.
AB  - A surface-enhanced Raman scattering (SERS)-fluorescence dual-mode pH-sensing
      method based on Janus microgels was developed, which combined the advantages of
      high specificity offered by SERS and fast imaging afforded by fluorescence. Dual
      mode probes, pH-dependent 4-mercaptobenzoic acid, and carbon dots were
      individually encapsulated in the independent hemispheres of Janus microparticles
      fabricated via a centrifugal microfluidic chip. On the basis of the obvious
      volumetric change of hydrogels in different pHs, the Janus microparticles were
      successfully applied for sensitive and reliable pH measurement from 1.0 to 8.0,
      and the two hemispheres showed no obvious interference. The proposed method
      addressed the limitation that sole use of the SERS-based pH sensing usually
      failed in strong acidic media. The gastric juice pH and extracellular pH change
      were measured separately in vitro using the Janus microparticles, which confirmed
      the validity of microgels for pH sensing. The microparticles exhibited good
      stability, reversibility, biocompatibility, and ideal semipermeability for
      avoiding protein contamination, and they have the potential to be implantable
      sensors to continuously monitor pH in vivo.

PMID- 29063751
TI  - Tannic Acid/Fe3+/Ag Nanofilm Exhibiting Superior Photodynamic and Physical
      Antibacterial Activity.
AB  - Silver nanoparticles (AgNPs) enwrapped in the biologically safe tannic acid
      (TA)/Fe3+ nanofilm are synthesized by an ultrafast, green, simple, and universal
      method. The physical antibacterial activity and photodynamic antibacterial
      therapy (PAT) efficacy of the TA/Fe3+/AgNPs nanofilm were investigated for the
      first time, which exhibited a strong physical antibacterial activity as well as
      great biocompatibility, through in vitro and in vivo studies. The results
      disclosed that this hybrid coating could possess high PAT capabilities upon
      irradiation under a visible light of 660 nm, which is longer than those of
      previously reported green and blue sensitization light, thus allowing deeper
      light penetration into biological tissues. Electron spin resonance (ESR) spectra
      proved that the PAT efficacy of the TA/Fe3+/AgNPs nanofilm was associated with
      the yields of singlet oxygen (1O2) under the irradiation of visible light (660
      nm). A higher PAT efficiency of 100 and 94% against Escherichia coli and
      Staphylococcus aureus could be achieved within 20 min of illumination under 660
      nm visible light, whereas the innate physical antibacterial activity of AgNPs
      could endow the implants with long-term prevention of bacterial infection. The
      mechanism of PAT may be associated with the formation of oxidative stress and
      oxidative damage to key biomolecules (proteins and lipids) in bacteria. Our
      results reveal that the synergistic action of both PAT and physical action of
      AgNPs in this hybrid nanofilm is an effective way to inactivate bacteria, with
      minimal side effects.

PMID- 29063752
TI  - Sub-10 nm Water-Dispersible beta-NaGdF4:X% Eu3+ Nanoparticles with Enhanced
      Biocompatibility for in Vivo X-ray Luminescence Computed Tomography.
AB  - As a novel molecular and functional imaging modality, X-ray luminescence computed
      tomography (XLCT) has shown its potentials in biomedical and preclinic
      applications. However, there are still some limitations of X-ray-excited
      luminescent materials, such as low luminescence efficiency, poor
      biocompatibility, and cytotoxicity, making in vivo XLCT imaging quite
      challenging. In this study, for the very first time, we present on using sub-10
      nm beta-NaGdF4:X% Eu3+ nanoparticles with poly(acrylic acid) (PAA) surface
      modification, which demonstrate outstanding luminescence efficiency, uniform size
      distribution, water dispersity, and biosafety, as the luminescent probes for in
      vivo XLCT application. The pure hexagonal phase (beta-) NaGdF4 has been
      successfully synthesized and characterized by X-ray powder diffraction (XRD) and
      transmission electron microscopy (TEM), and then the results of X-ray
      photoelectron spectroscopy (XPS), energy-dispersive X-ray spectrometry  (EDX),
      and elemental mapping further confirm Eu3+ ions doped into NaGdF4 host. Under X
      ray excitation, the beta-NaGdF4 nanoparticles with a doping level of 15% Eu3+
      exhibited the most efficient luminescence intensity. Notably, the doping level of
      Eu3+ has no effect on the crystal phase and morphology of the NaGdF4-based host.
      Afterward, beta-NaGdF4:15% Eu3+ nanoparticles were modified with PAA to enhance
      the water dispersity and biocompatibility. The compatibility of in vivo XLCT
      imaging using such nanoparticles was systematically studied via in vitro
      cytotoxicity, physical phantom, and in vivo imaging experiments. The ultralow
      cytotoxicity of PAA-modified nanoparticles, which is confirmed by over 80% cell
      viability of SH-SY5Y cells when treated by high nanoparticle concentration of 200
      MUg/mL, overcome the major obstacle for in vivo application. In addition, the
      high luminescence intensity of PAA-modified nanoparticles enables the location
      error of in vivo XLCT imaging less than 2 mm, which is comparable to that using
      commercially available bulk material Y2O3:15% Eu3+. The proposed nanoparticles
      promote XLCT research into an in vivo stage. Further modification of these
      nanoparticles with biofunctional molecules could enable the potential of
      targeting XLCT imaging.

PMID- 29063753
TI  - Visibility-Based PM2.5 Concentrations in China: 1957-1964 and 1973-2014.
AB  - China established ground PM2.5 monitoring network in late 2012 and hence the long
      term and large-scale PM2.5 data were lacking before 2013. In this work, we
      developed a national-scale spatiotemporal linear mixed effects model to estimate
      the long-term PM2.5 concentrations in China from 1957 to 1964 and from 1973 to
      2014 using ground visibility monitoring data as the primary predictor. The
      overall model-fitting and cross-validation R2 is 0.72 and 0.71, suggesting that
      the model is not overfitted. Validation beyond the model year (2014) indicated
      that the model could accurately estimate historical PM2.5 concentrations at the
      monthly (R2 = 0.71) level. The historical PM2.5 estimates suggest that air
      pollution is not a new environmental issue that occurs in the recent decades but
      a problem existing in a longer time before 1980. The PM2.5 concentrations have
      reached 60-80 MUg/m3 in the north part of North China Plain during 1950s-1960s
      and increased to generally higher than 90 MUg/m3 during 1970s. The results also
      show that the entire China experienced an overall increasing trend (0.19
      MUg/m3/yr, P < 0.001) in PM2.5 concentrations from 1957 to 2014 with fluctuations
      among different periods. This paper demonstrated visibility data allow us to
      understand the spatiotemporal characteristics of PM2.5 pollution in China in a
      long-term.

PMID- 29063754
TI  - Synthesis of Allahabadolactone A.
AB  - A synthesis of allahabadolactone A is described employing diastereoselective
      Diels-Alder and selenocyclization reactions, starting from (R)-citronellal and
      propylene oxide. The Diels-Alder substrate is built up in an efficient manner by
      rhodium-catalyzed alkyne hydroboration and palladium-catalyzed coupling reactions
      of E-1,2-dichloroethene. It is observed that the Diels-Alder reaction only
      displays high diastereoselectivity when the diene bears an additional alkene
      substituent but not an alkyne substituent.

PMID- 29063755
TI  - Analysis of Phenolic Compounds in Rooibos Tea (Aspalathus linearis) with a
      Comparison of Flavonoid-Based Compounds in Natural Populations of Plants from
      Different Regions.
AB  - Tea samples from 17 populations of "wild tea" ecotypes Aspalathus linearis
      (rooibos tea) and 2 populations of Aspalathus pendula were analyzed. Recent
      advances in column technology together with high-resolution mass spectrometry
      were applied to improve resolution, facilitating the identification of several
      new compounds as well as grouping of the wild tea ecotypes according to their
      chemical composition. The collisional cross-section data obtained from ion
      mobility-mass spectrometry is reported for the flavonoids in rooibos for the
      first time. Enzyme pathways for the synthesis of the unique flavonoids found in
      rooibos tea are also proposed. A. linearis and A. pendula produce similar
      combinations of main phenolic compounds, with no diagnostically different
      discontinuities between populations or species. Northern resprouters (Gifberg and
      Nieuwoudtville) contain higher phenylpropenoic acid glucoside levels while teas
      from Wupperthal and surrounding areas were found to contain unique
      dihydrochalcones (phloridzin and a sieboldin analog), which are reported here for
      the first time.

PMID- 29063756
TI  - Substrate-Dependent Two-State Reactivity in Iron-Catalyzed Alkene [2+2]
      Cycloaddition Reactions.
AB  - Iron-catalyzed alkene [2+2] cycloaddition reactions represent a promising
      stepwise pathway to effect the kinetically hindered concerted [2+2]
      cycloaddition. However, the fundamental reactivity paradigm of these reactions
      remains unclear. Based on high level combined CASPT2/DFT modelings, herein we
      reveal an unprecedented substrate-dependent two-state reactivity scenario for the
      key C-C coupling in this iron catalysis, in which the representative substrates
      of mono-olefins only and mono-olefin plus 1,3-diene exhibit different reactivity
      paradigms. The role of the redox-active ligand is found to generate a ferric
      oxidation state for the metallacyclic intermediate of C-C coupling, thereby
      rendering a thermodynamically more accessible FeIII/FeI reductive elimination
      process compared with the otherwise FeII/Fe0 one. The enhancement of the spin
      state transition efficiency between the singlet and triplet states is predicted
      as an alternative way to increase the C-C coupling reactivity in the cross [2+2]
      cycloaddition reactions between mono-olefins and dienes. This work highlights the
      ab initio multi-reference method in describing very complicated open-shell iron
      catalysis.

PMID- 29063758
TI  - Role of Electrical Double Layer Structure in Ionic Liquid Gated Devices.
AB  - Ionic liquid gating of transition metal oxides has enabled new states (magnetic,
      electronic, metal-insulator), providing fundamental insights into the physics of
      strongly correlated oxides. However, despite much research activity, little is
      known about the correlation of the structure of the liquids in contact with the
      transition metal oxide surface, its evolution with the applied electric
      potential, and its correlation with the measured electronic properties of the
      oxide. Here, we investigate the structure of an ionic liquid at a semiconducting
      oxide interface during the operation of a thin film transistor where the
      electrical double layer gates the device using experiment and theory. We show
      that the transition between the ON and OFF states of the amorphous indium gallium
      zinc oxide transistor is accompanied by a densification and preferential spatial
      orientation of counterions at the oxide channel surface. This process occurs in
      three distinct steps, corresponding to ion orientations, and consequently,
      regimes of different electrical conductivity. The reason for this can be found in
      the surface charge densities on the oxide surface when different ion arrangements
      are present. Overall, the field-effect gating process is elucidated in terms of
      the interfacial ionic liquid structure, and this provides unprecedented insight
      into the working of a liquid gated transistor linking the nanoscopic structure to
      the functional properties. This knowledge will enable both new ionic liquid
      design as well as advanced device concepts.

PMID- 29063757
TI  - Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran
      and the Effects on Immune Cell Binding and Stimulatory Characteristics.
AB  - Surface modifications of nanoparticles can alter their physical and biological
      properties significantly. They effect particle aggregation, circulation times,
      and cellular uptake. This is particularly critical for the interaction with
      primary immune cells due to their important role in particle processing. We can
      show that the introduction of a hydrophilic PEG layer on the surface of the
      polysaccharide-based nanoparticles prevents unwanted aggregation under
      physiological conditions and decreases unspecific cell uptake in different
      primary immune cell types. The opposite effect can be observed with a parallel
      performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa)
      on the particle surface (DEXylation) that encourages the nanoparticle uptake by
      antigen-presenting cells like macrophages and dendritic cells. Binding of
      DEXylated particles to these immune cells results in an upregulation of surface
      maturation markers and elevated production of proinflammatory cytokines,
      reflecting cell activation. Hence, DEXylated particles can potentially be used
      for passive targeting of antigen presenting cells with inherent adjuvant function
      for future immunotherapeutic applications.

PMID- 29063759
TI  - Enhancing Optoelectronic Properties of Low-Dimensional Halide Perovskite via
      Ultrasonic-Assisted Template Refinement.
AB  - Low-dimensional halide perovskite (HP) has triggered lots of research attention
      in recent years due to anisotropic optoelectronic/semiconducting properties and
      enhanced stability. High-quality low-dimensional HPs via controllable engineering
      are required to fulfill the encouraging promise for device applications. Here, we
      introduce, for the first time, postsynthetic ultrasonic-assisted refinement of
      two-dimensional homologous HPs (OA2PbBr4, OA is octadecylamine). The solution
      prepared OA2PbBr4, either in the form of large-sized microcrystal or nanosheet,
      obtains significantly enhanced crystallinity after ultrasonic treatment. We
      further show that OA2PbBr4 nanosheets can be used as a template to construct low
      dimensional CsPbBr3 with the size and morphology inherited. Importantly, we found
      the ultrasonic-treated OA2PbBr4 crystals, compared with pristine ones, lead to
      enhanced optoelectronic properties for the resultant low-dimensional CsPbBr3, as
      demonstrated by improved photodetection performances, including prolonged charge
      carrier lifetime, improved photostability, increased external quantum
      yield/responsivity, and faster response speed. We believe this work provides
      novel engineering of low-dimensional HPs beyond the reach of straightforward
      synthesis.

PMID- 29063761
TI  - Correction to "Time-Resolved Coherent Anti-Stokes Raman Scattering of Graphene:
      Dephasing Dynamics of Optical Phonon".

PMID- 29063760
TI  - A Two-Dimensional Biodegradable Niobium Carbide (MXene) for Photothermal Tumor
      Eradication in NIR-I and NIR-II Biowindows.
AB  - Conventionally, ceramics-based materials, fabricated by high-temperature solid
      phase reaction and sintering, are preferred as bone scaffolds in hard-tissue
      engineering because of their tunable biocompatibility and mechanical properties.
      However, their possible biomedical applications have rarely been considered,
      especially the cancer phototherapeutic applications in both the first and second
      near-infrared light (NIR-I and NIR-II) biowindows. In this work, we explore, for
      the first time as far as we know, a novel kind of 2D niobium carbide (Nb2C),
      MXene, with highly efficient in vivo photothermal ablation of mouse tumor
      xenografts in both NIR-I and NIR-II windows. The 2D Nb2C nanosheets (NSs) were
      fabricated by a facile and scalable two-step liquid exfoliation method combining
      stepwise delamination and intercalation procedures. The ultrathin, lateral
      nanosized Nb2C NSs exhibited extraordinarily high photothermal conversion
      efficiency (36.4% at NIR-I and 45.65% at NIR-II), as well as high photothermal
      stability. The Nb2C NSs intrinsically feature unique enzyme-responsive
      biodegradability to human myeloperoxidase, low phototoxicity, and high
      biocompatibility. Especially, these surface-engineered Nb2C NSs present highly
      efficient in vivo photothermal ablation and eradication of tumor in both NIR-I
      and NIR-II biowindows. This work significantly broadens the application prospects
      of 2D MXenes by rationally designing their compositions and exploring related
      physiochemical properties, especially on phototherapy of cancer.

PMID- 29063762
TI  - Highly Efficient Moisture-Triggered Nanogenerator Based on Graphene Quantum Dots.
AB  - A high-performance moisture triggered nanogenerator is fabricated by using
      graphene quantum dots (GQDs) as the active material. GQDs are prepared by direct
      oxidation and etching of natural graphite powder, which have small sizes of 2-5
      nm and abundant oxygen-containing functional groups. After the treatment by
      electrochemical polarization, the GQDs-based moisture triggered nanogenerator can
      deliver a high voltage up to 0.27 V under 70% relative humidity variation, and a
      power density of 1.86 mW cm-2 with an optimized load resistor. The latter value
      is much higher than the moisture-electric power generators reported previously.
      The GQD moisture triggered nanogenerator is promising for self-power electronics
      and miniature sensors.

PMID- 29063763
TI  - Scopranones with Two Atypical Scooplike Moieties Produced by Streptomyces sp. BYK
      11038.
AB  - Three new compounds, designated scopranones A-C, were isolated from the culture
      broth of a soil isolate, Streptomyces sp. BYK-11038, and shown to be inhibitors
      of bone morphogenetic protein (BMP) induced alkaline phosphatase activity in a
      BMP receptor mutant cell line. The structures were elucidated using NMR and other
      spectral data. The scopranones have an unusual structure with two atypical
      scooplike moieties linked at the tails to form part of a unique 3-furanone ring.

PMID- 29063764
TI  - Structural Disruption of an Adenosine-Binding DNA Aptamer on Graphene:
      Implications for Aptasensor Design.
AB  - We report on the predicted structural disruption of an adenosine-binding DNA
      aptamer adsorbed via noncovalent interactions on aqueous graphene. The use of
      surface-adsorbed biorecognition elements on device substrates is needed for
      integration in nanofluidic sensing platforms. Upon analyte binding, the
      conformational change in the adsorbed aptamer may perturb the surface properties,
      which is essential for the signal generation mechanism in the sensor. However, at
      present, these graphene-adsorbed aptamer structure(s) are unknown, and are
      challenging to experimentally elucidate. Here we use molecular dynamics
      simulations to investigate the structure and analyte-binding properties of this
      aptamer, in the presence and absence of adenosine, both free in solution and
      adsorbed at the aqueous graphene interface. We predict this aptamer to support a
      variety of stable binding modes, with direct base-graphene contact arising from
      regions located in the terminal bases, the centrally located binding pockets, and
      the distal loop region. Considerable retention of the in-solution aptamer
      structure in the adsorbed state indicates that strong intra-aptamer interactions
      compete with the graphene-aptamer interactions. However, in some adsorbed
      configurations the analyte adenosines detach from the binding pockets,
      facilitated by strong adenosine-graphene interactions.

PMID- 29063765
TI  - Directional Photonic Wire Mediated by Homo-Forster Resonance Energy Transfer on a
      DNA Origami Platform.
AB  - Elaborating efficient strategies and deepening the understanding of light
      transport at the nanoscale is of great importance for future designs of
      artificial light-harvesting assemblies and dye-based photonic circuits. In this
      work, we focus on studying the phenomenon of Forster resonance energy transfer
      (FRET) among fluorophores of the same kind (homo-FRET) and its implications for
      energy cascades containing two or three different dye molecules. Utilizing the
      spatial programmability of DNA origami, we arranged a chain of cyanine 3 (Cy3)
      dyes flanked at one end with a dye of lower excitation energy, cyanine 5 (Cy5),
      with or without an additional dye of higher excitation energy, Alexa488, at the
      other end. We characterized the response of our fluorophore assemblies with bulk
      and single-molecule spectroscopy and support our measurements by Monte Carlo
      modeling of energy transfer within the system. We find that, depending on the
      arrangement of the fluorophores, homo-FRET between the Cy3 dyes can lead to an
      overall enhanced energy transfer to the acceptor fluorophore. Furthermore, we
      systematically analyzed the homo-FRET system by addressing the fluorescence
      lifetime and anisotropy. Finally, we built a homo-FRET-mediated photonic wire
      capable of transferring energy through the homo-FRET system from the blue donor
      dye (Alexa488) to the red acceptor fluorophore (Cy5) across a total distance of
      16 nm.

PMID- 29063766
TI  - Accessing the Inaccessible: Analyzing the Oxygen Reduction Reaction in the
      Diffusion Limit.
AB  - The oxygen reduction reaction (ORR) is one of the key processes in
      electrocatalysis. In this communication, the ORR is studied using a rotating disk
      electrode (RDE). In conventional work, this method limits the potential region
      where kinetic (mass transport free) reaction rates can be determined to a narrow
      range. Here, we applied a new approach, which allows us to analyze the ORR rates
      in the diffusion-limited potential region of high mass transport. Thus, for the
      first time, the effect of anion adsorption on the ORR can be studied at such
      potentials.

PMID- 29063767
TI  - Detection and Analysis of Targeted Biological Cells by Electrophoretic Coulter
      Method.
AB  - Combining the electrophoresis and conventional Coulter methods, we previously
      proposed the electrophoretic Coulter method (ECM), enabling simultaneous analysis
      of the size, number, and zeta potential of individual specimens. We validated the
      ECM experimentally using standard polystyrene particles and red blood cells
      (RBCs) from sheep; the latter was the first ECM application to biological
      particles in biotechnology research. However, specimens are prevented from
      passing through the ECM module aperture, which prevents accurate determination of
      the zeta potential of each specimen. This problem is caused by electro-osmotic
      flow (EOF) due to the high zeta potential at the ECM microchannel surfaces. To
      significantly improve ECM feasibility for biomedicine, we here propose a method
      to estimate the zeta potential at the ECM microchannel surfaces separate from the
      zeta potential of each specimen, by investigating the electric-field dependence
      of the specimen's experimental electrophoretic velocity. We minimize the zeta
      potential at the microchannel surfaces by applying an organic-molecule coating,
      and we suppress the surface zeta potential and its resultant EOF by optimizing
      the microchannel geometry. We demonstrate that the ECM can distinguish between
      different biological cells using the differences in zeta potential values and/or
      sizes. We also demonstrate that the ECM can determine the number of biomolecules
      attached to individual cells and identify whether the average cell state in an
      analyzed vial is alive or dead. The high-performance ECM can detect cellular
      morphology alterations, improve immunologic test sensitivity, and identify cell
      states (living, dying, and dead); this information is clinically useful for early
      diagnosis and its follow-up.

PMID- 29063769
TI  - [Current application and future perspectives of capsule colonoscopy].
AB  - Colon capsule endoscopy (CCE) is a noninvasive technique for diagnostic imaging
      of the colon that does not require air insufflation or sedation. CCE can be used
      in average-risk patients, in patients with incomplete colonoscopy and in patients
      with contraindications for conventional colonoscopy. In this paper, we review the
      technical characteristics, current application and possible future development of
      CCE.Key words: colorectal cancer - screening colon capsule endoscopy.

PMID- 29063770
TI  - [Diagnosis of early pancreatic cancer and precursor lesions].
AB  - Pancreatic cancer is a malignancy, which usually carries a poor prognosis; the 5
      year survival is less than 6%. Therefore, its early detection in a stage when
      curable resection can be performed is essential to give the patients the best
      possible chance for a long-term survival. Despite the use of the most up-to-date
      diagnostic procedures, an early diagnosis of pancreatic carcinoma is rather
      unsuccessful. Furthermore, long-term survival rates for pancreatic cancer
      patients are still unsatisfactory, even when diagnosed early. Nevertheless,
      alterations occur in biomolecules as early as during the onset of oncogenesis,
      which can be detected by structure-sensitive spectroscopic methods. These methods
      provide a potential for detecting a sufficiently specific biomarker of early
      pancreatic carcinoma. A pilot study using molecular spectroscopy was conducted at
      the 1st Department of Internal Medicine, 1st Faculty of Medicine, Charles
      University and Military University Hospital in Prague, Czech Republic, in
      cooperation with the Department of Analytical Chemistry, University of Chemistry
      and Technology in Prague, Czech Republic. In the study, we compared the spectral
      response of blood plasma of patients with pancreatic carcinoma and healthy
      controls. Molecular spectroscopy provided evidence of significant differences
      between the two groups as illustrated by the study results. This approach thus
      might be suitable for detecting a specific biomarker of early pancreatic
      carcinoma. The findings have forced us to rethink the practical benefits of all
      potential biomarkers. In the future, we might face a situation where although any
      given marker is positive in a patient, no convincing morphological correlation
      can be found using available imaging methods. An important question is thus
      raised - whether or not to indicate surgical resection only on the basis of the
      biomarker positivity, and what type of resection to opt for.Key words: pancreatic
      cancer - early detection - spectroscopy - pancreatectomy.

PMID- 29063768
TI  - The Role of Repulsion in Colloidal Crystal Engineering with DNA.
AB  - Hybridization interactions between DNA-functionalized nanoparticles (DNA-NPs) can
      be used to program the crystallization behavior of superlattices, yielding access
      to complex three-dimensional structures with more than 30 different lattice
      symmetries. The first superlattice structures using DNA-NPs as building blocks
      were identified almost a decade ago, yet the role of repulsive interactions in
      guiding structure formation is still largely unexplored. Here, a comprehensive
      approach is taken to study the role of repulsion in the assembly behavior of DNA
      NPs, enabling the calculation of interparticle interaction potentials based on
      experimental results. In this work, we used two different means to assemble DNA
      NPs-Watson-Crick base-pairing interactions and depletion interactions-and
      systematically varied the salt concentration to study the effective interactions
      in DNA-NP superlattices. A comparison between the two systems allows us to
      decouple the repulsive forces from the attractive hybridization interactions that
      are sensitive to the ionic environment. We find that the gap distance between
      adjacent DNA-NPs follows a simple power law dependence on solution ionic strength
      regardless of the type of attractive forces present. This result suggests that
      the observed trend is driven by repulsive interactions. To better understand such
      behavior, we propose a mean-field model that provides a mathematical description
      for the observed trend. This model shows that the trend is due to the variation
      in the effective cross-sectional diameter of DNA duplex and the thickness of DNA
      shell.

PMID- 29063771
TI  - [Hamartoma of the abdominal cavity and retroperitoneum- a review and a case
      report].
AB  - METHODS: We have reviewed recent as well as older literature with the intention
      of compiling a summary report on hamartomas of the abdominal cavity and
      retroperitoneum. INTRODUCTION: Hamartoma of the abdominal cavity and
      retroperitoneum is a rare condition which has received relatively little
      attention. RESULTS: The most commonly affected organs are the liver, spleen,
      digestive tract, pancreas and kidneys. By its nature, hamartoma is a benign
      lesion with a good prognosis. However, neoplastic transformation may occur and
      hamartomas need to be regarded as potentially malignant. Patients are very often
      asymptomatic. Signs and symptoms depend on the organ involved and are caused, to
      different degrees, by obstruction, surrounding tissue compression, rupture or
      tumor bleeding. In imaging diagnostics, it is usually not possible to safely
      distinguish between a hamartoma and a malignant lesion. Therefore, the patient is
      preferably indicated for surgery (or endoscopic removal) for the purpose of
      histological verification and definitive treatment. CONCLUSION: Hamartomas of the
      abdominal cavity and retroperitoneum are relatively rare, benign and often
      asymptomatic diseases which, however, may manifest as compression, obstruction,
      perforation, bleeding or even malignant transformation. The recent case report of
      splenic hamartoma presented at the end of this review proves that surgical
      management is often the only rational option to obtain definitive confirmation of
      the diagnosis.Key words: splenic hamartoma hamartoma of the liver hamartoma of
      the pancreas hamartomatous polyps of the colon multiple hamartoma syndrome.

PMID- 29063772
TI  - [Omentum majus and milky spots as an important part of the immune system].
AB  - INTRODUCTION: Description and analysis of human omental milky spots is still not
      sufficiently clarified. In our study we describe the morphology of human omental
      milky spots and we also bring together a summary of the current knowledge of
      their function based on the available literature. METHOD: Samples of the omentum
      majus were collected preoperatively during surgical procedures in Vitkovice
      Hospital and subsequently subjected to further processing and histological
      analysis. Histological sections were stained with hematoxylin and eosin with a
      focus on the milky spots morphology and comparison of two groups of patients.
      RESULTS: Milky spots detected in the study were predominantly oval 56% (n=10),
      irregular in shape 28% (n=5) and round 16% (n=3). The average number of immune
      cells found in one milky spot in group A was 435 (194620). The average number of
      immune cells found in one milky spot in group B was 54 (40112). All milky spots
      were unencapsulated, macroscopically, they appear as furtive structures
      resembling white cotton balls. 72% (n=13) of milky spots were covered by
      mesothelial cells. CONCLUSION: Milky spots are small submesothelial lymphatic
      structures found in the omentum majus. They are in contact with the peritoneal
      cavity. They have their own vascular supply and no capsule. Our results show that
      the number and size of omental milky spots increase in patients with
      peritonitis.Key words: omentum majus milky spots - morphology surgery.

PMID- 29063774
TI  - [Massive bleeding in portal hypertension endoscopic, surgical or endovascular
      management?]
AB  - Upper gastrointestinal bleeding is a serious and potentially life-threatening
      abdominal emergency. An important diagnostic goal is to determine the cause and
      localize the bleeding site(s), which is crucial for choosing an appropriate
      therapy and consequently also for the long-term result. Our case report presents
      a patient with recurrent upper gastrointestinal bleeding where even repeated
      endoscopic, surgical and endovascular interventions were not sufficient to
      determinate the cause of bleeding and to save the patient's life.Key words:
      portal hypertension hepatic cirrhosis variceal bleeding ulcerative bleeding.

PMID- 29063773
TI  - [Pneumoperitoneum after colonoscopy - "to cut or not to cut"].
AB  - Colon perforation is a very serious complication of colonoscopy. The correct
      diagnosis and management of therapy improve the prognosis of patients. The
      treatment can be conservative, endoscopic and surgical. In this case report we
      present microperforation as a complication of polypectomy in the caecum during
      colonoscopy, followed by laparoscopic surgery.Key words: colonoscopy -
      complication -perforation polypectomy.

PMID- 29063775
TI  - [Combination of endoscopic mucosal resection and full-thickness resection in the
      treatment of local residual neoplasia of the colon two case reports].
AB  - We present the case of a 61-year-old patient with local residual neoplasia (LRN)
      of the rectum and the case of a 65-year-old patient with LRN of the cecum. In
      both cases, the lesion measured 25 mm in diameter and its center was fixed by
      submucosal fibrosis causing the non-lifting sign. For endoscopic treatment, which
      was uneventful,a combination of endoscopic mucosal resection (EMR) and full
      thickness resection (FTR) was used. In both cases, histological examination
      showed completely resected tubular adenoma with HGIN.Key words: colorectal
      carcinoma local residual neoplasia full-thickness resection endoscopic mucosal
      resection.

PMID- 29063777
TI  - [Articles of the Hungarian Medical Journal from May, 1997].

PMID- 29063776
TI  - [Articles of the Hungarian Medical Journal from April, 1997].

PMID- 29063779
TI  - [Articles of the Hungarian Medical Journal from November, 1997].

PMID- 29063778
TI  - [Articles of the Hungarian Medical Journal from June, 1997].

PMID- 29063781
TI  - [Articles of the Hungarian Medical Journal from December, 1997].

PMID- 29063782
TI  - Effects Of HIV stigma reduction interventions in diasporic communities: insights
      from the CHAMP study.
AB  - Racialized diasporic communities in Canada experience disproportionate burden of
      HIV infection. Their increased vulnerabilities are associated with interlocking
      challenges, including barriers in accessing resources, migration and settlement
      stress, and systemic exclusion. Further, people living with HIV (PLHIV) in these
      diasporic communities face stigma and discrimination in both mainstream Canadian
      society as well as their own ethno-racial communities. HIV stigma negatively
      impacts all aspects of HIV care, from testing to disclosure to treatment and
      ongoing care. In response to these challenges, a Toronto based community
      organization developed and implemented the CHAMP project to engage people living
      with HIV/AIDS (PLHIV) and leaders from different service sectors from the
      African/Caribbean, Asian and Latino communities to explore challenges and
      strategies to reduce HIV stigma and build community resilience. The study engaged
      66 PLHIV and ethno-racial leaders from faith, media and social justice sectors in
      two stigma-reduction training programs: Acceptance Commitment Therapy Training
      (ACT) and Social Justice Capacity Building (SJCB). Data collection included pre
      and post- intervention surveys, focus groups and monthly activity logs.
      Participants were followed for a year and data on changes in the participants'
      attitudes and behaviors as well as their actual engagement in HIV prevention,
      PLHIV support and stigma reduction activities were collected. CHAMP results
      showed that the interventions were effective in reducing HIV stigma and
      increasing participants' readiness to take action towards positive social change.
      Participants' activity logs over a period of 9 months after completing the
      training showed they had engaged in 1090 championship activities to advocate for
      HIV related health equity and social justice issues affecting racialized and
      newcomer PLHIV and communities.

PMID- 29063780
TI  - Transarterial chemoembolization with DC Bead LUMITM radiopaque beads for primary
      liver cancer treatment: preliminary experience.
AB  - AIM: Primary objectives of the study were to assess the safety of transarterial
      chemoembolization (TACE) using DC Bead LUMITM for the treatment of hepatocellular
      carcinoma and beads distribution after TACE. PATIENTS/METHODS: This was a
      prospective observational cohort study. The study included 44 hepatocellular
      carcinoma patients who were treated with TACE using DC Bead LUMI. Beads
      distribution was monitored 1 h after TACE by CT scan. RESULTS: TACE had no
      intraprocedural complications. Observed side effects were of mild intensity and
      included pain in 5 (11%), fever in 4 (9%) and vomiting in 2 (5%) patients. Most
      patients (89%) reported no adverse event. Non-target distribution was observed in
      only two cases (5%). CONCLUSION: DC Bead LUMI allowed assessing in real time
      their distribution. This could prevent non-target infusion and reduce toxicity.

PMID- 29063783
TI  - Iron therapy substantially restores qEEG maturational lag among iron-deficient
      anemic infants.
AB  - OBJECTIVE: To use quantitative electroencephalography (qEEG) to assess the impact
      of iron-deficiency anemia on central nervous system maturation in the first year
      of life. METHOD: Twenty-five infants (3-12 months old) presenting ferropenic
      anemia (IDA) and 25 healthy controls (CTL1), matched by age/gender with the
      former, were studied in two stages. Electroencephalogram during spontaneous sleep
      was recorded from all participants; the fast Fourier transform was calculated to
      obtain absolute power (AP) and relative power (RP) qEEG measures. In the first
      stage, a qEEG comparison between CTL1 and IDA was performed. Second stage
      consisted in comparing qEEG of the IDA infants before and after supplementation
      with iron (IDA-IS group), and comparing qEEG of the IDA-IS group with another
      control age-matched group (CTL2). Non-parametric multivariate permutation tests
      (NPT) were applied to assess differences between CTL1 and IDA groups, as well as
      IDA vs. IDA-IS, and IDA-IS vs. CTL2. RESULTS: More power in slow frequency bands
      and less power in fast frequency bands in 64% of IDA babies were observed. NPT
      evinced higher alpha AP and RP (P < 0.001), less theta AP, and less delta and
      theta RP in CTL1 than in IDA. After iron-restoration therapy, alpha AP and RP
      increased while theta AP and theta and delta RP decreased, reaching almost normal
      values. DISCUSSION: This work reveals CNS developmental delay through the study
      of qEEG (less rapid and more slow frequencies) which recovered significantly with
      iron supplementation. It is concluded that IDA constitutes a high risk factor for
      a lag of CNS maturation.

PMID- 29063784
TI  - [Articles of the Hungarian Medical Journal from August, 1997].

PMID- 29063785
TI  - [Articles of the Hungarian Medical Journal from October, 1997].

PMID- 29063787
TI  - Two new stilbenoids from aerial parts of Flickingeria fimbriata.
AB  - Two new stilbenoids, named 2,3 -dimethoxyl-7-hydroxyl-1,4-phenanthrenedione (1)
      and 2-methoxyl-3-methyl-7-hydroxyl-9,10-dihydro-1,4-phenanthrenedione (2),
      together with two known stilbenoids including densiflorol B (3) and
      ephemeranthoquinone (4), were isolated from aerial parts of Flickingeria
      fimbriata (Bl.) Hawkes. The structures of two new compounds were elucidated by
      extensive spectroscopic analysis, including HRESIMS, 1H and 13C NMR, DEPT, HMBC,
      COSY, HMQC, NOESY. All the compounds were obtained from this genus for the first
      time. In addition, they all exhibited moderate cytotoxic activities against HepG2
      cell lines.

PMID- 29063788
TI  - [Articles of the Hungarian Medical Journal from February, 1997].

PMID- 29063786
TI  - Light-activated phenalen-1-one bactericides: efficacy, toxicity and mechanism
      compared with benzalkonium chloride.
AB  - AIM: Five photoactive compounds with variable elongated alkyl-substituents in a
      phenalen-1-one structure were examined in view of structural similarity to the
      antimicrobial agent benzalkonium chloride (BAC). METHODS: All phenalen-1-ones and
      BAC were evaluated for their antimicrobial properties against Staphylococcus
      aureus, methicillin-resistant S. aureus, Escherichia coli, Pseudomonas aeruginosa
      and for their eukaryotic toxicity against normal human epidermal keratinocyte
      (NHEK) cells to narrow down the BAC-like effect and the photodynamic effect
      depending on the chemical structure. All compounds were investigated for
      effective concentration ranges, where a bacterial reduction of 5 log10 is
      achieved, while an NHEK survival of 80% is ensured. RESULTS: Effective
      concentration ranges were found for four out of five photoactive compounds, but
      not for BAC and the compound with BAC-like alkyl chain length. CONCLUSION: Chain
      length size and polar area of the respective head-groups of phenalen-1-one
      compounds or BAC showed an influence on the incorporation inside lipid membranes
      and thus, head-groups may have an impact on the toxicity of antimicrobials.

PMID- 29063789
TI  - Two new metabolites from Daldinia eschscholtzii, an endophytic fungus derived
      from Pogostemon cablin.
AB  - The chemical investigation of the mycelia of endophytic fungus Daldinia
      eschscholtzii A630, which was isolated from the medicinal plant Pogostemon
      cablin, resulted in the isolation of two new compounds, named eschscholin A (1),
      3-ene-2-methyl-2H-1-benzopyran-5-ol (2), and one new natural product 3,5
      dihydroxy-2-methyl-4H-chromen-4-one (3), along with seven known compounds. Their
      structures were fully characterized by means of detailed spectroscopic analysis,
      and in comparison with published data for known compounds. All of the isolated
      compounds (1-10) were evaluated for their antibacterial activities.

PMID- 29063790
TI  - Trauma and amyotrophic lateral sclerosis: a european population-based case
      control study from the EURALS consortium.
AB  - OBJECTIVES: To assess the association between amyotrophic lateral sclerosis (ALS)
      and previous traumatic events, age of trauma, and site of injury. METHODS: A
      population-based case-control study was performed in five European countries
      (Italy, Ireland, France, United Kingdom, Serbia). Newly diagnosed ALS patients
      and matched controls were interviewed to collect relevant demographic factors and
      exposures. Key clinical features at diagnosis were collected in ALS patients.
      Trauma was any accidental event causing an injury. Injuries were dated and
      classified according to cause, severity, type, site, and complications. All
      exposures were censored five years before symptoms onset. Risks were computed as
      odds ratios (OR) with 95% confidence intervals (CI) using univariate and
      multivariate conditional logistic regression models. RESULTS: Five hundred and
      seventy-five ALS patients and 1150 controls were interviewed. Disabling traumatic
      events predominated in the cases (OR 1.54 (95% CI 1.24-1.92)) and maintained
      significance after adjustment, with a significant gradient. A history of 2 + head
      injuries was associated with an almost three-fold increased risk of ALS. The risk
      was almost two-fold when trauma occurred at age 35-54 years. Site of injury was
      uneventful. CONCLUSIONS: Traumatic events leading to functional disability or
      confined to the head are risk factors for ALS. Traumatic events experienced at
      age 35-54 years carry the highest risk.

PMID- 29063791
TI  - Ginsenoside Rg3 micelles mitigate doxorubicin-induced cardiotoxicity and enhance
      its anticancer efficacy.
AB  - Doxorubicin (DOX) is one of the most effective chemotherapy agents used in the
      treatment of hematological and solid tumors, however, it causes dose-related
      cardiotoxicity that may lead to heart failure in patients. One of the major
      reasons was increased reactive oxygen species (ROS) production. Ginsenoside Rg3
      (Rg3), was powerful free radical scavengers and possessed cardioprotective
      effects. Nevertheless, Rg3 has low aqueous solubility and oral bioavailability,
      limiting its effects. Herein, we encapsulated Rg3 through spontaneous self
      assembly of Pluronic F127 to improve its solubility and oral bioavailability.
      Moreover, co-administering Rg3 in Pluronic F127 micelles with doxorubicin can
      mitigate the cardiotoxicity, with ameliorating mitochondrial and metabolic
      function, improving calcium handling, and decreasing ROS production. In addition,
      it can improve the anticancer efficacy of doxorubicin. Therefore, our study
      provides a rational strategy for further developing a potentially viable adjunct
      supportive treatment for reducing toxicity and increasing efficiency on
      chemotherapy.

PMID- 29063792
TI  - Synthesis and antitumor activity of a series of lactone-opened camptothecin
      derivatives.
AB  - A series of E-ring lactone-opened camptothecin (CPT) derivatives bearing with
      terminal aza-heterocyclic groups were synthesized, and their antitumor activity
      was evaluated both in vitro and in vivo. Hydroxyl-amide analogues with morpholin
      4-yl displayed excellent antitumor activity in vitro and efficient inhibition on
      tumor xenograph model in nude mice. Ester-amide compounds acted less active in
      vitro cytotoxicity and lower inhibition activity in vivo. Substitutions at 7- and
      10- positions favored the antitumor activity.

PMID- 29063793
TI  - The Participation Pyramid: a response to "Reconsideration ICF scheme" by Heerkens
      et al. 2017.

PMID- 29063794
TI  - Critical physicochemical and biological attributes of nanoemulsions for pulmonary
      delivery of rifampicin by nebulization technique in tuberculosis treatment.
AB  - The study investigated aerosolization, pulmonary inhalation, intracellular
      trafficking potential in macrophages and pharmacokinetics profiles of rifampicin
      oleic acid first-generation nanoemulsion and its respective chitosan- and
      chitosan-folate conjugate-decorated second and third-generation nanoemulsions,
      delivered via nebulization technique. The nanoemulsions were prepared by
      conjugate synthesis and spontaneous emulsification techniques. They were
      subjected to physicochemical, drug release, aerosolization, inhalation, cell
      culture and pharmacokinetics analysis. The nanoemulsions had average droplet
      sizes of 40-60 nm, with narrow polydispersity indices. They exhibited desirable
      pH, surface tension, viscosity, refractive index, density and viscosity
      attributes for pulmonary rifampicin administration. All nanoemulsions
      demonstrated more than 95% aerosol output and inhalation efficiency greater than
      75%. The aerosol output, aerosolized and inhaled fine particle fractions were
      primarily governed by the size and surface tension of nanoemulsions in an inverse
      relationship. The nanoemulsions were found to be safe with third-generation
      nanoemulsion exhibiting higher cell internalization potential, reduced plasma
      drug concentration, and higher lung drug content.

PMID- 29063796
TI  - [Articles of the Hungarian Medical Journal from July, 1997].

PMID- 29063795
TI  - Do shame and perfectionistic self-presentation explain the link between early
      affiliative memories and eating psychopathology?
AB  - This study tested a model examining the impact that early affiliative memories
      (both with family and peers) on eating psychopathology, and whether these links
      are carried by the mechanisms of external shame and body image-related
      perfectionistic self-presentation, in a sample of 480 female college students.
      Path analyses' results revealed that this model accounted for 48% of disordered
      eating's variance and suggests that the lack of early positive emotional memories
      is associated with higher levels of shame (feelings of inferiority and
      unattractiveness), and with higher tendency to adopt body image-related
      perfectionistic strategies, that seem to explain excessive eating concern and
      rigid control of one's eating behaviors. This study offers important insights for
      future research and for the development of intervention programs, by revealing
      the importance of assessing and targeting shame and perfectionistic strategies
      and suggesting the importance of promoting adaptive emotion regulation
      strategies.

PMID- 29063797
TI  - [Articles of the Hungarian Medical Journal from September, 1997].

PMID- 29063798
TI  - Design, synthesis and biological evaluation of chrysin benzimidazole derivatives
      as potential anticancer agents.
AB  - A series of chrysin benzimidazole derivatives were synthesised and evaluated for
      their anticancer activity in the search for potential anticancer agents. Among
      them, compound 18 displayed the most potent anti-proliferative activity against
      MFC cells with IC50 values of 25.72 +/- 3.95 MUM. The flow cytometry results
      displayed that compound 18 induced apoptosis of MFC cells in a dose-dependent
      manner and caused the cell cycle to be arrested in the G0/G1 phase. Furthermore,
      the preliminary anticancer activity in vivo was also studied in tumour-bearing
      mice, and the compound 18 exerted good inhibition effect on tumour growth. These
      results suggested that compound 18 had good anticancer activity, which could be a
      potential anticancer agent after further optimisation and evaluation.

PMID- 29063799
TI  - Genistein: mechanisms of action for a pleiotropic neuroprotective agent in
      stroke.
AB  - Genistein is a plant estrogen promoted as an alternative to post-menopausal
      hormone therapy because of a good safety profile and its promotion as a natural
      product. Several preclinical studies of cerebral ischemia and other models of
      brain injury support a beneficial role for genistein in protecting the brain from
      injury whether administered chronically or acutely. Like estrogen, genistein is a
      pleiotropic molecule that engages several different mechanisms to enhance brain
      health, including reduction of oxidative stress, promotion of growth factor
      signaling, and immune suppression. These actions occur in endothelial, glial, and
      neuronal cells to provide a coordinated beneficial action to ischemic challenge.
      Though many of these protective actions are associated with estrogen-like actions
      of genistein, additional activities on other receptors and intracellular targets
      suggest that genistein is more than a mere estrogen-mimic. Importantly, genistein
      lacks some of the detrimental effects associated with post-menopausal estrogen
      treatment and may provide an alternative to hormone therapy in those patients at
      risk for ischemic events.

PMID- 29063800
TI  - The development and evaluation of a web-based programme to support problem
      solving skills following brain injury.
AB  - BACKGROUND AND AIM: Cognitive impairments following brain injury, including
      difficulty with problem solving, can pose significant barriers to successful
      community reintegration. Problem-solving strategy training is well-supported in
      the cognitive rehabilitation literature. However, limitations in insurance
      reimbursement have resulted in fewer services to train such skills to mastery and
      to support generalization of those skills into everyday environments. The purpose
      of this project was to develop and evaluate an integrated, web-based programme,
      ProSolv, which uses a small number of coaching sessions to support problem
      solving in everyday life following brain injury. METHOD: We used participatory
      action research to guide the iterative development, usability testing, and within
      subject pilot testing of the ProSolv programme. The finalized programme was then
      evaluated in a between-subjects group study and a non-experimental single case
      study. RESULTS: Results were mixed across studies. Participants demonstrated that
      it was feasible to learn and use the ProSolv programme for support in problem
      solving. They highly recommended the programme to others and singled out the
      importance of the coach. Limitations in app design were cited as a major reason
      for infrequent use of the app outside of coaching sessions. CONCLUSIONS: Results
      provide mixed evidence regarding the utility of web-based mobile apps, such as
      ProSolv to support problem solving following brain injury. Implications for
      Rehabilitation People with cognitive impairments following brain injury often
      struggle with problem solving in everyday contexts. Research supports problem
      solving skills training following brain injury. Assistive technology for
      cognition (smartphones, selected apps) offers a means of supporting problem
      solving for this population. This project demonstrated the feasibility of a web
      based programme to address this need.

PMID- 29063801
TI  - "It's incredible how much I've had to fight." Negotiating medical uncertainty in
      clinical encounters.
AB  - PURPOSE: Clinical encounters related to medically unexplained physical symptoms
      (MUPS) are associated with high levels of conflict between patients and doctors.
      Collaborative difficulties are fused by the medical uncertainty that dominates
      these consultations. The main aim of this study is to explore the interactional
      dynamics of clinical encounters riddled by medical uncertainty, as experienced by
      people living with long-term medically unexplained fatigue in Norway. METHOD: A
      qualitative thematic analysis of written texts from 256 study participants.
      RESULTS: We found that patients experience being met with disbelief,
      inappropriate psychological explanations, marginalisation of experiences,
      disrespectful treatment, lack of physical examination and damaging health advice.
      The main source of their discontent is not the lack of biomedical knowledge, but
      doctors who fail to communicate acknowledgement of patients' experiences,
      knowledge and autonomy. War metaphors are emblematic of how participants describe
      their medical encounters. The overarching storyline depicts experiences of being
      caught in a power struggle with doctors and health systems, fused by a lack of
      common conceptual ground. CONCLUSION: When physical symptoms cannot be detected,
      explained and managed by biomedical knowledge and technology, good doctor-patient
      partnerships are crucial. Without clearly acknowledging patients' perspectives
      and capabilities in clinical practice, such partnerships cannot be achieved.

PMID- 29063802
TI  - Association between Mediterranean diet adherence and dyslipidaemia in a cohort of
      adults living in the Mediterranean area.
AB  - The aim of the present study was to determine the association between
      Mediterranean diet adherence and dyslipidaemia in a cohort of adults living in
      the Mediterranean area. The cross-sectional study comprised a total sample of
      2044 men and women, aged >18 years old from southern Italy. The Mediterranean
      diet adherence was assessed using a validated score (MEDI-LITE score). Clinical
      data were investigated and anthropometric examinations were collected using
      standardised methods. Among included individuals, 18.4% had dyslipidaemia. The
      percentage of females with dyslipidaemia was higher than males (21.2% vs. 14.6%).
      Higher adherence to Mediterranean diet was inversely associated with
      dyslipidaemia (OR: 0.56, 95% Cl: 0.36, 0.86). Similar association was observed in
      men, but not in women. On the contrary, a positive association was found between
      dyslipidaemia and current smoking and higher occupational status. Our results
      support the potential effectiveness of this diet in the prevention of
      dyslipidaemia and justify future intervention studies.

PMID- 29063803
TI  - Evaluation of chronic stress indicators in geriatric and oncologic caregivers: a
      cross-sectional study.
AB  - Caregiving induces chronic stress with physical and psychological impact on
      informal caregivers health. Therefore, subjective and objective indicators are
      needed for the early diagnosis of pathologic stress to prevent the risk of
      developing stress-related diseases in caregivers. Our aim was to assess the self
      perceived stress, that is, how and how much the stressor affects the individual,
      through endocrine, metabolic, and immunologic biomarkers levels in geriatric and
      oncologic informal caregivers. Informal caregivers and non-caregivers were
      invited to participate in a cross-sectional study at the Clinic Hospital of
      Barcelona. Demographic and lifestyle characteristics, self-perceived stress
      (Perceived Stress Scale, State-Trait Anxiety Inventory and Stress Visual Analogue
      Scale), and biomarkers (copeptin, glucose, glycated hemoglobin, low-density
      lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL),
      cholesterol, triglycerides, alpha-amylase, cortisol, tumor necrosis factor (TNF
      alpha), and Interleukins (IL-6 and IL-10)) were evaluated. Descriptive and non
      parametric statistical data analysis were performed. Fifty-six subjects (19 non
      caregivers, 17 geriatric caregivers, and 20 oncologic caregivers) participated.
      Median age (IQR) was 57 years (47-66) and 71.46% were women. Self-perceived
      stress was higher in oncologic caregivers than geriatric caregivers in all
      psychometric test analyzed (Wilcoxon Rank Sum test, p value < .05). Glucose
      concentrations and glycated hemoglobin levels differed statistically among groups
      (Kruskal-Wallis test (K-W tests), p value < .05), even though the median levels
      were not clinically relevant. Levels of other biomarkers did not differ
      significantly (K-W tests, p value > .05). These findings suggest that perceived
      stress is not homogeneous in the caregivers community and thus these two groups
      could be differentiated. These results provide the baseline information to
      initiate social actions addressed to each group of caregivers to increase their
      wellbeing.

PMID- 29063804
TI  - The pre-operative neutrophil-lymphocyte ratio predicts overall and disease-free
      survival following cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) in patients with pseudomxyoma peritonei of appendiceal
      origin.
AB  - AIM: The neutrophil-lymphocyte ratio (NLR) and other inflammation-based scores
      have been used as a prognostic tool to predict survival in solid tumours
      including pseudomyxoma peritonei (PMP). The aim was to evaluate the prognostic
      value of this marker and risk stratify PMP patients undergoing cytoreductive
      surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS:
      Retrospective analysis was conducted of a prospectively collected database of
      patients with PMP who underwent CRS and HIPEC between 1994 and 2015. The NLR was
      calculated by dividing the pre-operative neutrophil count by lymphocyte count.
      Predicted overall survival (OS) and disease-free interval (DFI) were calculated
      using a Kaplan-Meier survival model. RESULTS: The study included 699 patients,
      stratified into four groups as defined by their NLR. Group A: 200 (28.6%)
      patients (NLR = 0.10-2.00), Group B: 160 (22.8%) patients (NLR = 2.10-2.78),
      Group C: 184 (26.3%) patients (NLR = 2.79-4.31) and Group D: 155 (22.2%) patients
      (NLR >= 4.32). The median follow-up for this cohort was 36 months. The predicted
      DFI was 132.2, 113.1, 84.4 and 47.9 months and the OS was 141.1, 117.6, 88.7 and
      51.2 months for Groups A, B, C and D, respectively. As the NLR increases, there
      is a reduction in long-term survival. CONCLUSION: The pre-operative NLR is cost
      effective and has equivalent prognostic value to pre-operative tumour markers for
      patients with PMP treated with CRS and HIPEC. The NLR is a reliable tool that may
      have a role in predicting outcomes following CRS and HIPEC for patients with PMP
      of appendiceal origin.

PMID- 29063805
TI  - Telomere length in poor-risk chronic lymphocytic leukemia: associations with
      disease characteristics and outcome.
AB  - Telomere length in chronic lymphocytic leukemia (CLL) is described as an
      independent prognostic factor based largely on previously untreated patients from
      chemotherapy based trials. Here, we studied telomere length associations in high
      risk, relapsed/refractory CLL treated with alemtuzumab in the CLL2O study (n =
      110) of German and French CLL study groups. Telomere length (median 3.28 kb,
      range 2.52-7.24 kb) was relatively short, since 84.4% of patients had 17p- which
      is generally associated with short telomeres. Median telomere length was used for
      dichotomization into short and long telomere subgroups. Telomere length was
      associated with s-TK (p = .025) and TP53 mutations (p = .050) in untreated
      patients, while no association with clinical/biological characteristics was
      observed in relapsed/refractory CLL. Short telomeres had significant association
      with shorter PFS (p = .018) only in refractory CLL. Presence of short telomeres,
      loss of genes maintaining genomic integrity (SMC5) and increased incidence of
      chromothripsis, indicated the prevalence of genomic instability in this high-risk
      cohort (clinicaltrials.gov: NCT01392079).

PMID- 29063806
TI  - Does a Mediterranean-type dietary pattern exert a cardio-protective effect
      outside the Mediterranean region? A review of current evidence.
AB  - Current evidence suggests a beneficial effect of the Mediterranean diet (MD) on
      human health. This has led to a rise in studies investigating the role of the MD
      in cardiovascular disease (CVD) prevention outside the region of its origin. We
      aimed to outline the evolving understanding of the MD and to provide an overview
      of adherence to MD in non-Mediterranean countries and the modulatory effects of
      MD on CVD biomarkers. Evidence suggest that MD may exert a protective effect on
      CVD via ameliorating blood lipid profile and blood pressure. A protective effect
      of MD was found with regard to left ventricular mass but data on carotid intima
      media thickness and pulse wave velocity are lacking. The paucity of data does not
      give a clear picture of the health effects of the MD in non-Mediterranean
      countries, thus larger and well-designed studies on MD outside the Mediterranean
      countries are warranted.

PMID- 29063808
TI  - Hugo L. Obwegeser (1920-2017) - The father of modern orthognathic surgery.

PMID- 29063807
TI  - Unilateral pleural effusion as the sole clinical presentation of severe ovarian
      hyperstimulation syndrome: a systematic review.
AB  - The pathophysiology of isolated pleural effusion in ovarian hyperstimulation
      syndrome (OHSS) is not well defined. The objective of the current review is to
      delineate the pathophysiology, risk factors, preventive measures, and therapeutic
      options of isolated pleural effusion in severe OHSS. Major databases were
      searched until June 2016. Studies evaluating women who presented with pleural
      effusion as the sole extra-ovarian manifestation of severe OHSS were included.
      Data were extracted from 24 articles encompassing 30 reported cases. Values were
      expressed as mean +/- SEM. Patients were young (31.5 +/- 0.8 years old) and 29.1%
      of them were diagnosed with polycystic ovary syndrome. All the patients received
      human chorionic gonadotropin to trigger oocyte maturation. Estradiol level was
      3110 +/- 330 pg/mL on the day of the ovulatory trigger. Dyspnea was the
      presenting symptom in 86.6% of the patients. Pleural effusion was predominantly
      on the right side (80%). Ninety percent of the patients underwent thoracentesis
      (4332 +/- 769 mL): 66.7% exudate and 33.3% transudate. Fluid initially
      accumulates in the peritoneal cavity then enters the pleural space due to the
      pressure gradient through the thoracic duct and diaphragmatic defects, which are
      more common on the right side. The risk factors, prevention, and management,
      which are also discussed in this review, are similar to those of severe OHSS.

PMID- 29063809
TI  - Thoracic gamma irradiation-induced obesity in C57BL/6 female mice.
AB  - PURPOSE: To investigate the late effects of thoracic region irradiation (TRI) on
      mouse body weight. MATERIALS AND METHODS: Female C57BL/6 mice were divided into
      nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and
      12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were
      monitored every other week at similar time points for 12 months. The anatomical
      characteristics of abdominal visceral fat distribution were recorded, and
      mitochondrial DNA copy number in the hearts and livers and lipid metabolic
      signaling in the liver were analyzed. Data were analyzed by one-way analysis of
      variance and a student's t-test. RESULTS: TRI led to a significant increase (p <
      .001) in body weight that was dependent on time and individuals [42.1% of mice
      were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice
      were overweight at 10 months post-TRI]. Gross anatomical features of abdominal
      visceral fat distribution and storage in radiation-induced overweight/severely
      overweight mice were similar to those of high fat diet-induced
      overweight/severely overweight mice. The mitochondrial genome of heart and liver
      tissues from overweight/severely overweight mice had significantly (p < .05)
      decreased functional mitochondrial DNA copy number (ratios decreased from 1 to
      0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial
      DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and
      IRS2 lipid metabolic signaling was significantly (p < .05-.01) decreased for both
      mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold
      decrease from 1 to 0.62 or 0.19, respectively). CONCLUSIONS: TRI can cause mice
      to gain weight. These findings indicate that TRI can result in lipid metabolic
      abnormalities and provide a model to study the factors that result in these
      abnormalities.

PMID- 29063810
TI  - The use of uHearTM to screen for hearing loss in older patients with cancer as
      part of a comprehensive geriatric assessment.
AB  - OBJECTIVE: We previously validated uHearTM to screen for hearing loss in older
      patients with cancer without a known hearing loss, as part of a comprehensive
      geriatric assessment (CGA). In view of low specificity, we tested a new modified
      uHearTM scoring system as described by Handzel. METHODS: Patients, aged >=70
      years, were evaluated by uHearTM and conventional audiometry, which is considered
      the gold standard, as part of a CGA. The pass or fail screening cut-off for
      uHearTM was defined as having >=2 consecutive hearing grades starting from the
      moderate-severe threshold zone ranging from 0.5 to 2.0 kHz (modified Handzel
      uHearTM scoring system). To accept the modified Handzel-uHearTM as screening
      tool, it was predefined that the combined sensitivity (S) and specificity (Sp) of
      the test (S + Sp/2) was at least 80% and that an actual combined (S + Sp)/2 of
      90% would be found. RESULTS: Ninety ears (45 subjects) were tested. Of those
      ears, 24.4% were identified as impaired by conventional audiometry. Modified
      Handzel-uHearTM identified 26.7% of tested ears as impaired. The combined (S +
      Sp)/2 of the modified Handzel-uHearTM was calculated as 77.5%, while in previous
      cohort, this was retrospectively calculated as 94.6%. A new uHearTM scoring
      system was proposed and tested in current and previous cohort. A (S + Sp)/2 of
      80.2 and 78.8%, respectively, were obtained. CONCLUSION: uHearTM is a feasible
      tool for use within the CGA and shows promising results. However, further
      research is warranted to optimize the cut-off method before it could be routinely
      implemented within geriatric oncology.

PMID- 29063811
TI  - Emergence of colistin resistance in Enterobacter aerogenes from Croatia.
AB  - A colistin-resistant Enterobacter aerogenes [study code 12264] was isolated from
      the tracheal aspirate of a 71-year-old male patient in the General Hospital [GH]
      in Pula, Croatia. The patient was previously treated in University Hospital
      Centre in Rijeka with colistin in order to eradicate Acinetobacter baumannii
      isolate, susceptible only to colistin and tigecycline. Genes encoding ESBLs
      [blaTEM, blaSHV, blaCTX-M, blaPER-1] were screened by PCR. The strain was shown
      to possess blaCTX-M-15 and blaTEM-1 genes. To asses genes possibly involved in
      resistance to colistin the chromosomal enconding mgrB gene and the plasmid
      mediated mcr-1 and mcr-2 genes were screened as described previously. Mcr-1 and
      mcr-2 genes were not detected and mgrB gene presented a wild-type sequence. PCR
      based Replicon typing method [PBRT] conducted on an E. aerogenes isolate, showed
      that the strain carried an IncN plasmid. Adaptive mechanisms such as changes of
      the bacterial cell outer membrane that cause porin decrease or presence of an
      efflux pump, due to selection pressure exerted by the therapeutic administration
      of colistin, could be responsible for the development of colistin resistance in
      our strain, as recently reported in E. aerogenes from France. Due to effective
      infection control measures, the colistin-resistant strain did not spread to other
      patients or hospital wards. This is the first report of an ESBL-producing,
      colistin-resistant E. aerogenes in clinically relevant samples such as
      endotracheal aspirate and blood culture, showing the presence of this rare
      resistance profile among Gram-negative bacteria.

PMID- 29063812
TI  - Reorganized neural activation in motor cortex following subdural fluid
      collection: an fMRI and DTI study.
AB  - We report a patient with a cavernous malformation involving the right lentiform
      nucleus. Pre-surgical planning included fMRI localization of language, motor, and
      sensory processing, and DTI of white matter tracts. fMRI results revealed no
      activation near the planned resection zone. However, post-surgery the patient
      developed a subdural fluid collection, which applied pressure to the primary
      motor cortex (M1). Follow-up scans revealed that motor activation had shifted due
      to pressure, and then shifted to a new location after the fluid collection
      subsided. This case report suggests that long-term neural reorganization can
      occur in response to short term compression in the cortex.

PMID- 29063814
TI  - The use of cannabidiol for seizure management in patients with brain tumor
      related epilepsy.
AB  - Epilepsy, commonly encountered by patients with brain tumors, is often refractory
      to standard therapies. Our aim was to examine the safety and efficacy of
      pharmaceutical grade cannabidiol (CBD; Epidiolex; Greenwich Biosciences) in those
      patients with epilepsy with concomitant tumors enrolled in The University of
      Alabama at Birmingham CBD Program (NCT02700412 and NCT02695537). Of the three
      patients with refractory seizures and a history of a primary brain tumor, two had
      improvement in seizure frequency and all three had improvement in seizure
      severity. These pilot results suggest that CBD should be further studied for the
      treatment of brain tumor-related epilepsy.

PMID- 29063815
TI  - N-acetyl-L-cysteine functionalized nanostructured lipid carrier for improving
      oral bioavailability of curcumin: preparation, in vitro and in vivo evaluations.
AB  - The application of orally administered nanoparticles in the circulation system is
      limited by the secretion and shedding of intestinal tract mucous layer. In order
      to enhance mucoadhesion and mucus penetration of curcumin (Cur)-loaded
      nanostructured lipid carrier (NLC) after oral administration, a new
      multifunctional conjugate, N-acetyl-L-cysteine-polyethylene glycol (100)
      monostearate (NAPG), was synthesized. Functionalized nanocarriers (Cur-NAPG-NLC)
      modified by different amounts of NAPG (the amounts of NAPG were 20, 50, and 100
      mg) were prepared and investigated for in vitro and in vivo behavior. Mean
      particle sizes of 89-141 nm with negative zeta potential (-15 to -11 mV) and high
      encapsulation efficiency (EE, >90%) possessing spherical and stable nanocarriers
      were observed. Sustained drug release was also observed for the NAPG-NLC. In situ
      intestinal perfusion studies showed that with increasing the amount of NAPG
      increase absorption of Cur. In vivo oral pharmacokinetic evaluation suggested
      that the bioavailability of Cur in rats was proportional to the degree of
      functionalization of NLCs with NAPG. AUC0-t of Cur-NAPG100-NLC was improved by
      499.45 and 116.89 folds as compared to that of Cur solution and unmodified Cur
      NLC, respectively. In conclusion, NAPG modified NLC could be a promising drug
      delivery system for improving oral performance of BCS class IV drugs.

PMID- 29063813
TI  - The eIF2-alpha kinase HRI: a potential target beyond the red blood cell.
AB  - INTRODUCTION: The eIF2alpha kinase heme-regulated inhibitor (HRI) is one of four
      well-described kinases that phosphorylate eIF2alpha in response to various cell
      stressors, resulting in reduced ternary complex formation and attenuation of mRNA
      translation. Although HRI is well known for its role as a heme sensor in
      erythroid progenitors, pharmacologic activation of HRI has been demonstrated to
      have anti-cancer activity across a wide range of tumor sub-types. Here, the
      potential of HRI activators as novel cancer therapeutics is explored. Areas
      covered: We provide an introduction to eIF2 signaling pathways in general, and
      specifically review data on the eIF2alpha kinase HRI in erythroid and non
      erythroid cells. We review aspects of targeting eIF2 signaling in cancer and
      highlight promising data using HRI activators against tumor cells. Expert
      opinion: Pharmacologic activation of HRI inhibits tumor growth as a single agent
      without appreciable toxicity in vivo. The ability of HRI activators to provide
      direct and sustained eIF2alpha phosphorylation without inducing oxidative stress
      or broad eIF2alpha kinase activation may be especially advantageous for
      tolerability. Combination therapy with established therapeutics may further
      augment anti-cancer activity to overcome disease resistance.

PMID- 29063816
TI  - Stress analysis of irradiated human tooth enamel using finite element methods.
AB  - The objectives of this project were to use finite element methods to determine
      how changes in the elastic modulus due to oral cancer therapeutic radiation alter
      the distribution of mechanical stresses in teeth and to determine if observed
      failures in irradiated teeth correlate with changes in mechanical stresses. A
      thin slice section finite element (FE) model was constructed from micro CT
      sections of a molar tooth using MIMICS and 3-Matic software. This model divides
      the tooth into three enamel regions, the dentin-enamel junction (DEJ) and dentin.
      The enamel elastic modulus was determined in each region using nano indentation
      for three experimental groups namely - control (non-radiated), in vitro
      irradiated (simulated radiotherapy following tooth extraction) and in vivo
      irradiated (extracted subsequent to oral cancer patient radiotherapy) teeth.
      Physiological loads were applied to the tooth models at the buccal and lingual
      cusp regions for all three groups (control, in vitro and in vivo). The principal
      tensile stress and the maximum shear stress were used to compare the results from
      different groups since it has been observed in previous studies that delamination
      of enamel from the underlying dentin was one of the major reasons for the failure
      of teeth following therapeutic radiation. From the FE data, we observed an
      increase in the principal tensile stress within the inner enamel region of in
      vivo irradiated teeth (9.97 +/- 1.32 MPa) as compared to control/non-irradiated
      teeth (8.44 +/- 1.57 MPa). Our model predicts that failure occurs at the inner
      enamel/DEJ interface due to extremely high tensile and maximum shear stresses in
      in vivo irradiated teeth which could be a cause of enamel delamination due to
      radiotherapy.

PMID- 29063818
TI  - The efficacy of a pilot pediatric cognitive remediation summer program to prepare
      for transition of care.
AB  - This study assessed the efficacy of a time-sensitive cognitive remediation summer
      program (CRSP) that provided patients and their families with tools to help
      mitigate neurocognitive deficits and promote independence to foster precursor
      transition of medical care skills. A total of 38 participants (aged 9-15) were
      included in one of the CRSPs offered yearly from 2013 to 2016. A longitudinal
      design was employed and at each evaluation time point, one week before start of
      the CRSP (pre-testing) and within three weeks after the end of the program (post
      testing)), participants were administered measures of executive functioning in
      addition to parent ratings of behavior, executive functioning, and adaptive
      skills (Year 1-Year 4). In Year 4, additional measures were collected, including
      parenting style and parent engagement and involvement in the program. Results
      from Year 1 to Year 4 (n = 35) demonstrated that participants in the CRSP showed
      significant improvement on neuropsychological testing in sustained and selective
      attention, planning, and cognitive flexibility. Robust changes in parent ratings
      of adaptive functioning from pre- to post-treatment were also found. Specific to
      Year 4 (n = 13), results revealed that participants showed improvement in levels
      of independence with at least one of the individualized goals focused on during
      the program. This study provided a systematic method to gauge the levels of
      instruction necessary to reach goals, a crucial tool in skill-teaching. Overall,
      our study provides evidence for the efficacy of the CRSP and validates a feasible
      intervention that can be integrated into standard of care for pediatric medical
      populations.

PMID- 29063817
TI  - The intersection of intimate partner violence and HIV risk among women engaging
      in transactional sex in Ugandan fishing villages.
AB  - Intimate partner violence (IPV) may increase risk for HIV/AIDS among women
      engaging in transactional sex in Ugandan fishing communities. In this cross
      sectional study, 115 women reporting engaging in transactional sex in Lake
      Victoria fishing communities completed a computerized interview. We tested
      associations between IPV and other HIV risk factors, with unprotected sex and HIV
      status, and tested moderators of the IPV-HIV risk relationship. Women reporting
      recent sexual IPV reported 3.36 times more unprotected sex acts (AdjExp[B] =
      3.36, 95% CI = 1.29-8.69, p = 0.07). The effect of sexual IPV on sexual risk was
      significantly greater among alcohol and fish sellers compared to sex workers
      (interaction: Exp[B] = 12.29, 95% CI = 5.06-29.85, p < 0.001). Women reporting
      any sexual IPV were nearly four times more likely to report being HIV positive
      than women reporting no sexual IPV (AOR = 3.94, 95% CI = 1.22-12.66, p = 0.02).
      Integrated IPV and HIV interventions are needed in this context, especially among
      alcohol and fish sellers engaging in transactional sex.

PMID- 29063819
TI  - Investigation of the effects of various antibiotics against Klebsiella pneumoniae
      biofilms on in vitro catheter model.
AB  - Klebsiella pneumoniae continues to be an important cause of community-acquired
      and nosocomial infection. This bacterium can cause catheter related infections by
      forming biofilm on the surface of catheter. The aim of our study is to determine
      the in vitro stability and efficacy of colistin, ciprofloxacin, tobramycin,
      doripenem and tigecycline alone, or in combination with clarithromycin or
      esomeprazole, as 24-h lock solutions against biofilm-embedded K. pneumoniae
      strains. The efficacy of antibiotic lock solutions was tested in an in vitro
      catheter biofilm model against K. pneumoniae. In our study, we observed that the
      use of doripenem and tobramycin as a lock solution had potent bactericidal
      effects. When colistin was used in combination with clarithromycin or
      esomeprazole, the combinations had a synergistic effect. No antagonistic effect
      was observed. The findings of our study have important information for
      effectiveness of tested antibiotic lock solution in the catheter-related
      infections with K. pneumoniae.

PMID- 29063820
TI  - F240 of beta2-Tubulin Explains why Fusarium graminearum is Less Sensitive to
      Carbendazim than Botrytis cinerea.
AB  - beta-Tubulin is the target of benzimidazole fungicides, the most widely used of
      which is carbendazim (methyl benzimidazol-2-ylcarbamate [MBC]). MBC sensitivity
      is determined by the differential affinity of MBC for beta-tubulins. However, the
      mechanism of less sensitivity of Fusarium graminearum to MBC compared with other
      fungi, including Botrytis cinerea, Colletotrichum gloeosporioides, and
      Sclerotinia sclerotiorum, remains exclusive. Alignment of beta-tubulin amino acid
      sequences showed that position 240 of beta-tubulins is leucine (L) in most
      pathogenic fungi but is phenylalanine (F) in the Fgbeta2-tubulin of the F.
      graminearum wild type. The effective concentration resulting in 50% inhibition
      (EC50) value of MBC against the Fgbeta2F240L mutant of F. graminearum is 0.047
      MUg/ml, which was 10-fold lower than that of wild-type strain 2021. Moreover, The
      EC50 value of MBC against the BcbetaL"240"F (actually position 232) mutant of
      Botrytis cinerea was 0.44 MUg/ml, which was ninefold higher than that of B.
      cinerea wild-type strain Bt4-1. In response to MBC treatment (0.15 MUg/ml),
      microtubules were clearly visible in Fgbeta2-enhanced green fluorescent protein
      (EGFP) but not in Fgbeta2F240L-EGFP. Moreover, a molecular docking assay
      indicated that F240L mutation created a pi-pi interaction between Fgbeta2-tubulin
      and MBC and increased the binding affinity of Fgbeta2-tubulin to MBC. Our results
      suggest that F240 is responsible for the naturally less MBC sensitivity in F.
      graminearum compared with B. cinerea, C. gloeosporioides, and S. sclerotiorum by
      decreasing the binding affinity between Fgbeta2-tubulin and MBC.

PMID- 29063821
TI  - Single Nucleotide Polymorphisms in B-Genome Specific UDP-Glucosyl Transferases
      Associated with Fusarium Head Blight Resistance and Reduced Deoxynivalenol
      Accumulation in Wheat Grain.
AB  - An in vitro spike culture method was optimized to evaluate Fusarium head blight
      (FHB) resistance in wheat (Triticum aestivum) and used to screen a population of
      ethyl methane sulfonate treated spike culture-derived variants (SCDV). Of the 134
      SCDV evaluated, the disease severity score of 47 of the variants was <=30%.
      Single nucleotide polymorphisms (SNP) in the UDP-glucosyltransferase (UGT) genes,
      TaUGT-2B, TaUGT-3B, and TaUGT-EST, differed between AC Nanda (an FHB-susceptible
      wheat variety) and Sumai-3 (an FHB-resistant wheat cultivar). SNP at 450 and
      1,558 bp from the translation initiation site in TaUGT-2B and TaUGT-3B,
      respectively were negatively correlated with FHB severity in the SCDV population,
      whereas the SNP in TaUGT-EST was not associated with FHB severity. Fusarium
      graminearum strain M7-07-1 induced early expression of TaUGT-2B and TaUGT-3B in
      FHB-resistant SCDV lines, which were associated with deoxynivalenol accumulation
      and reduced FHB disease progression. At 8 days after inoculation, deoxynivalenol
      concentration varied from 767 ppm in FHB-resistant variants to 2,576 ppm in FHB
      susceptible variants. The FHB-resistant SCDV identified can be used as new
      sources of FHB resistance in wheat improvement programs.

PMID- 29063822
TI  - Comparison of Marker-Based Genomic Estimated Breeding Values and Phenotypic
      Evaluation for Selection of Bacterial Spot Resistance in Tomato.
AB  - Bacterial spot affects tomato crops (Solanum lycopersicum) grown under humid
      conditions. Major genes and quantitative trait loci (QTL) for resistance have
      been described, and multiple loci from diverse sources need to be combined to
      improve disease control. We investigated genomic selection (GS) prediction models
      for resistance to Xanthomonas euvesicatoria and experimentally evaluated the
      accuracy of these models. The training population consisted of 109 families
      combining resistance from four sources and directionally selected from a
      population of 1,100 individuals. The families were evaluated on a plot basis in
      replicated inoculated trials and genotyped with single nucleotide polymorphisms
      (SNP). We compared the prediction ability of models developed with 14 to 387 SNP.
      Genomic estimated breeding values (GEBV) were derived using Bayesian least
      absolute shrinkage and selection operator regression (BL) and ridge regression
      (RR). Evaluations were based on leave-one-out cross validation and on empirical
      observations in replicated field trials using the next generation of inbred
      progeny and a hybrid population resulting from selections in the training
      population. Prediction ability was evaluated based on correlations between GEBV
      and phenotypes (rg), percentage of coselection between genomic and phenotypic
      selection, and relative efficiency of selection (rg/rp). Results were similar
      with BL and RR models. Models using only markers previously identified as
      significantly associated with resistance but weighted based on GEBV and mixed
      models with markers associated with resistance treated as fixed effects and
      markers distributed in the genome treated as random effects offered greater
      accuracy and a high percentage of coselection. The accuracy of these models to
      predict the performance of progeny and hybrids exceeded the accuracy of
      phenotypic selection.

PMID- 29063823
TI  - Age differences in vocal emotion perception: on the role of speaker age and
      listener sex.
AB  - Older adults have greater difficulty than younger adults perceiving vocal
      emotions. To better characterise this effect, we explored its relation to age
      differences in sensory, cognitive and emotional functioning. Additionally, we
      examined the role of speaker age and listener sex. Participants (N = 163) aged 19
      34 years and 60-85 years categorised neutral sentences spoken by ten younger and
      ten older speakers with a happy, neutral, sad, or angry voice. Acoustic analyses
      indicated that expressions from younger and older speakers denoted the intended
      emotion with similar accuracy. As expected, younger participants outperformed
      older participants and this effect was statistically mediated by an age-related
      decline in both optimism and working-memory. Additionally, age differences in
      emotion perception were larger for younger as compared to older speakers and a
      better perception of younger as compared to older speakers was greater in younger
      as compared to older participants. Last, a female perception benefit was less
      pervasive in the older than the younger group. Together, these findings suggest
      that the role of age for emotion perception is multi-faceted. It is linked to
      emotional and cognitive change, to processing biases that benefit young and own
      age expressions, and to the different aptitudes of women and men.

PMID- 29063824
TI  - Time to redefine body mass index categories in chronic diseases? Spotlight on
      obesity paradox.
AB  - Obesity is a complex condition classically characterised by excessive body fat
      accumulation and represents one of the most important public health problems
      worldwide. Although several epidemiological studies have shown that elevated BMI
      is associated with higher morbidity, and with increased rate of death from all
      causes and from cardiovascular disease, accumulating evidence suggests that being
      overweight or obese may be protective (the so-called obesity paradox), at least
      in chronic diseases. These observations, not only question the validity of the
      BMI system, but also raise the intriguing question of whether we should redefine
      what the normal range of BMI is in individuals suffering from a chronic disease.
      In the present article, we review the available information on the association
      between elevated BMI and increased morbidity and mortality including obesity
      related paradoxes, explore key aspects of the role and limitations of BMI as a
      measure of increased adiposity and outline potential solutions to address the
      current controversies regarding the impact of obesity on human health.

PMID- 29063825
TI  - Target visualisation and microwave hyperthermia monitoring using nanoparticle
      enhanced transmission ultrasound (NETUS).
AB  - PURPOSE: The aim of this study was to examine the feasibility of using
      nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based
      monitoring modality for microwave hyperthermia treatment. METHODS: A dedicated
      transmission ultrasound imaging system was used to obtain acoustic projections
      and ultrasound computed tomography images. Initially, speed-of-sound based images
      were used to non-invasively monitor temperature changes in in vitro and ex vivo
      specimens, induced by a microwave needle-type applicator. Next, the hyperthermia
      acceleration ability of two ultrasound nanoparticles based contrast agents (iron
      oxide and copper oxide) was examined and visualised. Finally, a two-step image
      guided microwave therapeutic procedure using NETUS was investigated in a
      realistic breast mimicking phantom. First, the pathology simulating region
      borders were detected. Then, a microwave-induced temperature elevation was non
      invasively monitored. RESULTS: The transmission ultrasound scanning system was
      able to detect temperature changes with a resolution of less than 0.5  degrees C,
      both in vitro and ex vivo. In accordance with previous studies, it was visually
      demonstrated that iron oxide nanoparticles expedite the heating process (p <
      0.05). Copper oxide nanoparticles, however, did not alter the hyperthermia
      profile significantly. In the breast mimicking phantom, NETUS yielded accurate
      detection of the target region as well as thermal monitoring of the microwave
      heating procedure. CONCLUSIONS: NETUS can combine enhanced target visualisation
      with non-invasive thermometry and accelerated heating effect. Quantitative
      feedback, however, requires a tissue-specific calibration-curve. A proof of
      concept for microwave hyperthermia treatment monitoring using NETUS was
      established. The suggested methodology may potentially provide a non-invasive
      cost-effective means for monitoring thermal treatment of the breast.

PMID- 29063826
TI  - Degradative treatment of bispyribac sodium herbicide from synthetically
      contaminated water by colloidal MnO2 dioxide in the absence and presence of
      surfactants.
AB  - Bispyribac sodium (BS) is one of the most commonly used herbicides used to kill
      selectively unwanted herbs particularly in rice plantation. However, the
      increasing use of herbicides in agricultural field is associated with a potential
      risk to water resources and aquatic system. Thus, the treatment of such
      pesticides after fulfillment of their herbicidal activity is of quite interest to
      minimize the contamination of water. The degradation kinetics of BS from
      synthetic contaminated water by water-soluble colloidal MnO2 in acidic medium
      (HClO4) has been studied spectrophotometrically in the absence and presence of
      different surfactants. The degradation has been observed to be fractionally
      ordered in both BS and HClO4 under pseudo-first-order reaction condition with
      respect to MnO2. The anionic surfactant (sodium dodecyl sulfate) has been
      observed to be ineffective whereas the cationic surfactant (cetyltrimethyl
      ammonium bromide) causes flocculation with oppositely charged colloidal MnO2 and
      therefore could not be studied further. However, the non-ionic surfactant (Triton
      X-100) has been observed to accelerate the reaction rate. The catalytic effect of
      this surfactant has been analyzed and discussed in the light of the available
      mathematical model. The kinetic data have been used to generate the various
      activation parameters accompanying the degradation process of BS in the absence
      and presence of the non-ionic surfactant, Triton X-100.

PMID- 29063827
TI  - Subcutaneous Injection of Adalimumab Trial compared with Control (SCIATiC): a
      randomised controlled trial of adalimumab injection compared with placebo for
      patients receiving physiotherapy treatment for sciatica.
AB  - BACKGROUND: Biological treatments such as adalimumab (Humira(r); AbbVie Ltd,
      Maidenhead, UK) are antibodies targeting tumour necrosis factor alpha, released
      from ruptured intervertebral discs, which might be useful in sciatica. Recent
      systematic reviews concluded that they might be effective, but that a definitive
      randomised controlled trial was needed. Usual care in the NHS typically includes
      a physiotherapy intervention. OBJECTIVES: To test whether or not injections of
      adalimumab plus physiotherapy are more clinically effective and cost-effective
      than injections of saline plus physiotherapy for patients with sciatica. DESIGN:
      Pragmatic, parallel-group, randomised controlled trial with blinded participants
      and clinicians, and an outcome assessment and statistical analysis with
      concurrent economic evaluation and internal pilot. SETTING: Participants were
      referred from primary care and musculoskeletal services to outpatient
      physiotherapy clinics. PARTICIPANTS: Adults with persistent symptoms of sciatica
      of 1-6 months' duration and with moderate to high levels of disability.
      Eligibility was assessed by research physiotherapists according to clinical
      criteria for diagnosing sciatica. INTERVENTIONS: After a second eligibility
      check, trial participants were randomised to receive two doses of adalimumab (80
      mg and then 40 mg 2 weeks later) or saline injections. Both groups were referred
      for a course of physiotherapy. MAIN OUTCOME MEASURES: Outcomes were measured at
      the start, and after 6 weeks' and 6 months' follow-up. The main outcome measure
      was the Oswestry Disability Index (ODI). Other outcomes: leg pain version of the
      Roland-Morris Disability Questionnaire, Sciatica Bothersomeness Index, EuroQol-5
      Dimensions, 5-level version, Hospital Anxiety and Depression Scale, resource use,
      risk of persistent disabling pain, pain trajectory based on a single question,
      Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia and adverse
      effects. SAMPLE SIZE: To detect an effect size of 0.4 with 90% power, a 5%
      significance level for a two-tailed t-test and 80% retention rate, 332
      participants would have needed to be recruited. ANALYSIS PLAN: The primary
      effectiveness analysis would have been linear mixed models for repeated measures
      to measure the effects of time and group allocation. An internal pilot study
      would have involved the first 50 participants recruited across all centres. The
      primary economic analysis would have been a cost-utility analysis. RESULTS: The
      internal pilot study was discontinued as a result of low recruitment after eight
      participants were recruited from two out of six sites. One site withdrew from the
      study before recruitment started, one site did not complete contract negotiations
      and two sites signed contracts shortly before trial closure. In the two sites
      that did recruit participants, recruitment was slow. This was partly because of
      operational issues, but also because of a low rate of uptake from potential
      participants. LIMITATIONS: Although large numbers of invitations were sent to
      potential participants, identified by retrospective searches of general
      practitioner (GP) records, there was a low rate of uptake. Two sites planned to
      recruit participants during GP consultations but opened too late to recruit any
      participants. CONCLUSION: The main failure was attributable to problems with
      contracts. Because of this we were not able to complete the internal pilot or to
      test all of the different methods for primary care recruitment we had planned. A
      trial of biological therapy in patients with sciatica still needs to be done, but
      would require a clearer contracting process, qualitative research to ensure that
      patients would be willing to participate, and simpler recruitment methods. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN14569274. FUNDING: This project was
      funded by the National Institute for Health Research (NIHR) Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 21, No. 60. See the NIHR Journals Library website for further
      project information.

PMID- 29063828
TI  - Assessment of the insecticidal activity of afoxolaner against Aedes aegypti in
      dogs treated with NexGard(r).
AB  - Twelve healthy dogs were studied in this parallel group, blinded, randomised, and
      negative controlled efficacy study. On Day -1, the 12 dogs included were ranked
      within sex in descending order of individual pre-treatment (Day -5) fed mosquito
      counts and randomly allocated by blocks of two dogs to the untreated control
      group or the afoxolaner-treated group. NexGard(r) (Merial, now part of Boehringer
      Ingelheim Animal Health) was administered orally on Day 0 in accordance with the
      European label instructions. On Days 1, 7, 14, 21 and 28, all dogs were exposed
      for a duration of 1 hour to 50 +/- 5 unfed Aedes aegypti females. After each
      exposure, mosquitoes were collected after 1 hour and assessed for viability
      during collection and at 24 +/- 2 hours. The arithmetic (and geometric) mean
      values of live fed mosquito counts at 24 hours after the exposure periods for the
      negative control group ranged from 33.7 (32.3) to 49.8 (49.7), indicating that
      this was a vigorous mosquito strain. There was no significant difference between
      control and treated groups in the number of live and fed mosquitoes at each 1
      hour post-exposure collection time. Based on arithmetic and geometric mean values
      at 24 hours after each exposure, significantly fewer live fed mosquitoes were
      recorded in the treated group, compared to the negative control group, throughout
      the study (p < 0.001). The afoxolaner insecticidal efficacy against A. aegypti
      varied from 98% (Day 2) to 75.3% (Day 29) based on arithmetic means, and 98.7%
      (Day 2) to 89.8% (Day 29) based on geometric means.

PMID- 29063829
TI  - A transcriptional switch controls meiosis.
AB  - A key protein involved in the segregation of meiotic chromosomes is produced
      'just in time' by the regulated expression of two mRNA isoforms.

PMID- 29063830
TI  - Many si/shRNAs can kill cancer cells by targeting multiple survival genes through
      an off-target mechanism.
AB  - Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand
      (CD95L) induce a form of cell death characterized by simultaneous activation of
      multiple cell death pathways preferentially killing transformed and cancer stem
      cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by
      targeting the 3'UTR of critical survival genes in a unique form of off-target
      effect we call DISE (death induced by survival gene elimination). Drosha and
      Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE,
      suggesting cellular miRNAs protect cells from this form of cell death. By testing
      4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated
      control gene, Venus, we have identified many toxic sequences - most of them
      located in the open reading frame of CD95L. We propose that specific toxic RNAi
      active sequences present in the genome can kill cancer cells.

PMID- 29063831
TI  - Theta-burst microstimulation in the human entorhinal area improves memory
      specificity.
AB  - The hippocampus is critical for episodic memory, and synaptic changes induced by
      long-term potentiation (LTP) are thought to underlie memory formation. In
      rodents, hippocampal LTP may be induced through electrical stimulation of the
      perforant path. To test whether similar techniques could improve episodic memory
      in humans, we implemented a microstimulation technique that allowed delivery of
      low-current electrical stimulation via 100 MUm-diameter microelectrodes. As
      thirteen neurosurgical patients performed a person recognition task,
      microstimulation was applied in a theta-burst pattern, shown to optimally induce
      LTP. Microstimulation in the right entorhinal area during learning significantly
      improved subsequent memory specificity for novel portraits; participants were
      able both to recognize previously-viewed photos and reject similar lures. These
      results suggest that microstimulation with physiologic level currents-a radical
      departure from commonly used deep brain stimulation protocols-is sufficient to
      modulate human behavior and provides an avenue for refined interrogation of the
      circuits involved in human memory.

PMID- 29063832
TI  - daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to
      support survival.
AB  - daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how
      daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO
      restructures carbohydrate metabolism by driving carbon flux through the
      glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a
      disaccharide of glucose. Trehalose is a well-known stress protectant, capable of
      preserving membrane organization and protein structure during abiotic stress.
      Metabolomic, genetic, and pharmacological analyses confirm increased trehalose
      synthesis and further show that trehalose not only supports survival as a stress
      protectant but also serves as a glycolytic input. Furthermore, we provide
      evidence that metabolic cycling between trehalose and glucose is necessary for
      this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes
      starvation resistance by shifting carbon metabolism to drive trehalose synthesis,
      which in turn supports survival by providing an energy source and acting as a
      stress protectant.

PMID- 29063833
TI  - SAV1 promotes Hippo kinase activation through antagonizing the PP2A phosphatase
      STRIPAK.
AB  - The Hippo pathway controls tissue growth and homeostasis through a central MST
      LATS kinase cascade. The scaffold protein SAV1 promotes the activation of this
      kinase cascade, but the molecular mechanisms remain unknown. Here, we discover
      SAV1-mediated inhibition of the PP2A complex STRIPAKSLMAP as a key mechanism of
      MST1/2 activation. SLMAP binding to autophosphorylated MST2 linker recruits
      STRIPAK and promotes PP2A-mediated dephosphorylation of MST2 at the activation
      loop. Our structural and biochemical studies reveal that SAV1 and MST2
      heterodimerize through their SARAH domains. Two SAV1-MST2 heterodimers further
      dimerize through SAV1 WW domains to form a heterotetramer, in which MST2
      undergoes trans-autophosphorylation. SAV1 directly binds to STRIPAK and inhibits
      its phosphatase activity, protecting MST2 activation-loop phosphorylation.
      Genetic ablation of SLMAP in human cells leads to spontaneous activation of the
      Hippo pathway and alleviates the need for SAV1 in Hippo signaling. Thus, SAV1
      promotes Hippo activation through counteracting the STRIPAKSLMAP PP2A phosphatase
      complex.

PMID- 29063834
TI  - What's in a name?
AB  - Numerous concerns have been raised about the sustainability of the biomedical
      research enterprise in the United States. Improving the postdoctoral training
      experience is seen as a priority in addressing these concerns, but even
      identifying who the postdocs are is made difficult by the multitude of different
      job titles they can carry. Here, we summarize the detrimental effects that
      current employment structures have on training, compensation and benefits for
      postdocs, and argue that academic research institutions should standardize the
      categorization and treatment of postdocs. We also present brief case studies of
      two institutions that have addressed these challenges and can provide models for
      other institutions attempting to enhance their postdoctoral workforces and
      improve the sustainability of the biomedical research enterprise.

PMID- 29063835
TI  - Two single-point mutations shift the ligand selectivity of a pheromone receptor
      between two closely related moth species.
AB  - Male moths possess highly sensitive and selective olfactory systems that detect
      sex pheromones produced by their females. Pheromone receptors (PRs) play a key
      role in this process. The PR HassOr14b is found to be tuned to (Z)-9-hexadecenal,
      the major sex-pheromone component, in Helicoverpa assulta. HassOr14b is co
      localized with HassOr6 or HassOr16 in two olfactory sensory neurons within the
      same sensilla. As HarmOr14b, the ortholog of HassOr14b in the closely related
      species Helicoverpa armigera, is tuned to another chemical (Z)-9-tetradecenal, we
      study the amino acid residues that determine their ligand selectivity. Two amino
      acids located in the transmembrane domains F232I and T355I together determine the
      functional difference between the two orthologs. We conclude that species
      specific changes in the tuning specificity of the PRs in the two Helicoverpa moth
      species could be achieved with just a few amino acid substitutions, which
      provides new insights into the evolution of closely related moth species.

PMID- 29063837
TI  - Differences in Normal Tissue Response in the Esophagus Between Proton and Photon
      Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging
      Biomarkers.
AB  - PURPOSE: To determine whether there exists any significant difference in normal
      tissue toxicity between intensity modulated radiation therapy (IMRT) or proton
      therapy for the treatment of non-small cell lung cancer. METHODS AND MATERIALS: A
      total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT)
      treated in a randomized trial had a previously validated esophageal toxicity
      imaging biomarker, esophageal expansion, quantified during radiation therapy, as
      well as esophagitis grade (Common Terminology Criteria for Adverse Events version
      3.0), on a weekly basis during treatment. Differences between the 2 modalities
      were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis
      analysis of variance), as well as the incidence and severity of esophagitis grade
      (chi2 and Fisher exact tests, respectively). The dose-response of the imaging
      biomarker was also compared between modalities using esophageal equivalent
      uniform dose, as well as delivered dose to an isotropic esophageal subvolume.
      RESULTS: No statistically significant difference in the distribution of
      esophagitis grade, the incidence of grade >=3 esophagitis (15 and 11 patients
      treated with IMRT and proton therapy, respectively), or the esophageal expansion
      imaging biomarker between cohorts (P>.05) was found. The distribution of imaging
      biomarker metric values had similar distributions between treatment arms, despite
      a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose
      response was similar between modalities for dose quantified as esophageal
      equivalent uniform dose and delivered esophageal subvolume dose. Regardless of
      treatment modality, there was high variability in imaging biomarker response, as
      well as esophagitis grade, for similar esophageal doses between patients.
      CONCLUSIONS: There was no significant difference in esophageal toxicity from
      either proton- or photon-based radiation therapy as quantified by esophagitis
      grade or the esophageal expansion imaging biomarker.

PMID- 29063836
TI  - Patient-specific mutations impair BESTROPHIN1's essential role in mediating Ca2+
      dependent Cl- currents in human RPE.
AB  - Mutations in the human BEST1 gene lead to retinal degenerative diseases
      displaying progressive vision loss and even blindness. BESTROPHIN1, encoded by
      BEST1, is predominantly expressed in retinal pigment epithelium (RPE), but its
      physiological role has been a mystery for the last two decades. Using a patient
      specific iPSC-based disease model and interdisciplinary approaches, we
      comprehensively analyzed two distinct BEST1 patient mutations, and discovered
      mechanistic correlations between patient clinical phenotypes, electrophysiology
      in their RPEs, and the structure and function of BESTROPHIN1 mutant channels. Our
      results revealed that the disease-causing mechanism of BEST1 mutations is
      centered on the indispensable role of BESTROPHIN1 in mediating the long
      speculated Ca2+-dependent Cl- current in RPE, and demonstrate that the
      pathological potential of BEST1 mutations can be evaluated and predicted with our
      iPSC-based 'disease-in-a-dish' approach. Moreover, we demonstrated that patient
      RPE is rescuable with viral gene supplementation, providing a proof-of-concept
      for curing BEST1-associated diseases.

PMID- 29063838
TI  - Toward Personalized Dosimetry with 32P Microparticle Therapy for Advanced
      Pancreatic Cancer.
AB  - PURPOSE: To develop a Monte Carlo model for patient-specific dosimetry of 32P
      microparticle localized internal radionuclide therapy for advanced pancreatic
      cancer. METHODS AND MATERIALS: Spherical tumor geometries and a pancreatic
      phantom were modeled, as well as different 3-dimensional non-uniform clinical
      pancreatic geometries based on patient-specific ultrasound images. The dosimetry
      simulations modeled the dose distribution due to the energy spectrum of emitted
      beta particles. RESULTS: The average dose for small (3-cm diameter) and large (6
      cm diameter) spherical tumors was 111 Gy (for 7.6 MBq administered activity) and
      128 Gy (for 58 MBq), respectively. For the clinical 3-dimensional geometries, on
      the basis of patient data, the mean doses delivered to the tumor were calculated
      to be in the range 102 to 113 Gy, with negligible dose to the pancreas for the
      smallest tumor volumes. The calculated dose distributions are highly non-uniform.
      For the largest tumor studied, the pancreas received approximately 6% of the
      tumor dose (5.7 Gy). Importantly, we found that because the smallest tumor
      studied exhibited the most dynamic changes in volume in response to the
      treatment, the dose to tumor and pancreas is significantly underestimated if a
      static tumor volume is assumed. CONCLUSIONS: These results demonstrate the
      dosimetry of 32P microparticle localized internal radionuclide therapy for
      pancreatic cancer and the possibility of developing personalized treatment
      strategies. The results also highlight the importance of considering the effects
      of non-uniform dose distributions and dynamic change of tumor mass during
      treatment on the dosimetry of the tumor and critical organs.

PMID- 29063839
TI  - In Regard to Likhacheva et al.

PMID- 29063840
TI  - In Reply to Liu and Li.

PMID- 29063841
TI  - Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer: The Hunt
      for the Silver Bullet.

PMID- 29063842
TI  - The Prickly Predicament of Pursuing Pulmonary Polymetastases.

PMID- 29063844
TI  - Let "Whitmore's Principle" be the Guide.

PMID- 29063845
TI  - Metastasis-Directed Therapy: Right for Some, but Not All, and Not Here.

PMID- 29063843
TI  - SABR Given Thoughtfully.

PMID- 29063846
TI  - Give Resection a Chance.

PMID- 29063847
TI  - Avoid Futile Therapy.

PMID- 29063848
TI  - Neoadjuvant Chemoradiation in the Treatment of Locally Advanced Breast Cancer.

PMID- 29063849
TI  - Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection
      in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal
      Field Design for Adjuvant Radiation Therapy.
AB  - PURPOSE: To identify prognostic factors and patterns of local failure in patients
      with cholangiocarcinoma (CCA), after surgical resection in the absence of
      adjuvant radiation, for optimal definition of target volumes encompassing the
      majority of local recurrences. METHODS AND MATERIALS: A chart review was
      performed in patients who underwent resection for primary CCA (intrahepatic,
      hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence
      in a theoretical reasonable postoperative radiation volume. This includes the cut
      surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri
      pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who
      received adjuvant radiation were excluded. RESULTS: A total of 189 patients
      underwent surgical resection for CCA, of whom 145 patients had sufficient follow
      up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months).
      Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant
      chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine
      based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%)
      had a locoregional component. Among patients who had a recurrence, 23 (27%) had a
      recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight
      patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in
      the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis
      identified tumor size, any vascular invasion, presence of satellites, stage/nodal
      status, and receipt of chemotherapy as significant prognostic factors of overall
      recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx
      status remained statistically significant in multivariable modeling. CONCLUSIONS:
      The areas at highest risk for locoregional recurrence after surgical resection
      for primary CCA are the biliary anastomosis/cut liver surface, portal lymph
      nodes, and retroperitoneal lymph nodes. Although these results need to be
      validated, adjuvant radiation should possibly cover these areas to maximize
      locoregional control.

PMID- 29063851
TI  - Development and Internal Validation of a Clinical Risk Score to Predict Pain
      Response After Palliative Radiation Therapy in Patients With Bone Metastases.
AB  - PURPOSE: To investigate the relationship between patient and tumor
      characteristics and pain response in patients with metastatic bone disease, and
      construct and internally validate a clinical prediction model for pain response
      to guide individualized treatment decision making. MATERIAL AND METHODS: A total
      of 965 patients with painful bone metastases undergoing palliative radiation
      therapy at a tertiary referral center between 1999 and 2007 were identified. Pain
      scores were measured at 1, 2, and 3 months after radiation therapy. Pain response
      was defined as at least a 2-point decrease on a pain score scale of 0-10, without
      increase in analgesics, or an analgesic decrease of at least 25% without an
      increase in pain score. Thirteen candidate predictors were identified from the
      literature and expert experience. After multiple imputation, final predictors
      were selected using stepwise regression and collapsed into a prediction model.
      Model performance was evaluated by calibration and discrimination and corrected
      for optimism. RESULTS: Overall 462 patients (47.9%) showed a response. Primary
      tumor site, performance status, and baseline pain score were predictive for pain
      response, with a corrected c-statistic of 0.63. The predicted response rates
      after radiation therapy increased from 37.5% for patients with the highest risk
      score to 79.8% for patients with the lowest risk score and were in good agreement
      with the observed response rates. CONCLUSIONS: A prediction score for pain
      response after palliative radiation therapy was developed. The model performance
      was moderate, showing that prediction of pain response is difficult. New
      biomarkers and predictors may lead to improved identification of the large group
      of patients who are unlikely to respond and who may benefit from other or
      innovative treatment options.

PMID- 29063852
TI  - Local Control Outcomes Using Stereotactic Body Radiation Therapy for Liver
      Metastases From Colorectal Cancer.
AB  - PURPOSE: To evaluate the effective dose and patterns of recurrence after
      stereotactic body radiation therapy (SBRT) for hepatic metastases that arise from
      colorectal cancer. METHODS AND MATERIALS: A cohort of 70 patients with 103
      colorectal liver metastases were treated with SBRT at a single institution. The
      prescribed doses were 45 to 60 Gy in 3 to 4 fractions, but these were modified
      according to the tolerance of the adjacent normal tissue. To allow for dose
      comparisons, a biological equivalent dose was calculated. RESULTS: The median
      follow-up period was 34.2 months (range, 5.3-121.8 months). The 2-year overall
      survival and progression-free survival rates were 75% and 35%, respectively. In
      subgroups, the 2-year local control rates for biological equivalent dose <=80 Gy
      (group 1), 100 to 112 Gy (group 2), and >=132 Gy (group 3) were 52%, 83%, and
      89%, respectively. Cox proportional hazards model revealed a significant
      difference between groups (hazard ratio 0.44, P=.03 for group 2; hazard ratio
      0.17, P=.17 for group 3; P=.01 for total). The major pattern of failure was a new
      liver metastasis out of the SBRT field. There was no grade >=3 toxicity.
      CONCLUSIONS: Stereotactic body radiation therapy of liver metastases derived from
      colorectal cancer offers a locally effective treatment without significant
      complications. Longer local control can be expected if higher doses are used.
      Further studies will be needed to compare the efficacies of SBRT with those of
      surgical resection or radiofrequency ablation.

PMID- 29063850
TI  - Estimating Survival in Melanoma Patients With Brain Metastases: An Update of the
      Graded Prognostic Assessment for Melanoma Using Molecular Markers (Melanoma
      molGPA).
AB  - PURPOSE: To update the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA)
      for a markedly heterogeneous patient population, patients with melanoma and brain
      metastases, using a larger, more current cohort, including molecular markers.
      METHODS: The original Melanoma-GPA is based on data from 483 patients whose
      conditions were diagnosed between 1985 and 2005. This is a multi-institutional
      retrospective database analysis of 823 melanoma patients with newly diagnosed
      brain metastases from January 1, 2006, to December 31, 2015. Multivariable
      analyses identified significant prognostic factors, which were weighted and
      included in the updated index (Melanoma-molGPA). Multiple Cox regression was used
      to select and weight prognostic factors in proportion to their hazard ratios to
      design the updated Melanoma-molGPA in which scores of 4.0 and 0.0 are associated
      with the best and worst prognoses, as with all of the diagnosis-specific GPA
      indices. Log-rank tests were used to compare adjacent classes. RESULTS: There
      were 5 significant prognostic factors for survival (age, Karnofsky performance
      status [KPS], extracranial metastases [ECM], number of brain metastases, and BRAF
      status), whereas only KPS and the number of brain metastases were significant in
      the original Melanoma-GPA. Median survival improved from 6.7 to 9.8 months
      between the 2 treatment eras, and the median survival times for patients with
      Melanoma-molGPA of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 4.9,
      8.3, 15.8, and 34.1 months (P<.0001 between each adjacent group). CONCLUSIONS:
      Survival and our ability to estimate survival in melanoma patients with brain
      metastases has improved significantly. The updated Melanoma-molGPA, a user
      friendly tool to estimate survival, will facilitate clinical decision making
      regarding whether and which treatment is appropriate and will also be useful for
      stratification of future clinical trials. To further simplify use, a free
      online/smart phone app is available at brainmetgpa.com.

PMID- 29063853
TI  - Lack of Benefit From the Addition of External Beam Radiation Therapy to
      Brachytherapy for Intermediate- and High-risk Prostate Cancer.
AB  - PURPOSE: A recent randomized controlled trial demonstrated that the addition of
      external beam radiation therapy (EBRT) to brachytherapy did not improve
      progression-free survival in select patients with intermediate-risk prostate
      cancer. We evaluated whether the addition of EBRT to brachytherapy improves
      prostate cancer-specific mortality (PCSM) for intermediate- and high-risk disease
      using a large national database. METHODS AND MATERIALS: We identified 5836
      patients in the Surveillance, Epidemiology, and End Results-Medicare linked
      database with a diagnosis of National Comprehensive Cancer Network intermediate
      risk (Gleason score 7, prostate-specific antigen 10-20 ng/mL, or stage cT2b-T2c)
      or high-risk (Gleason score 8-10 or prostate-specific antigen >20 ng/mL and stage
      <=cT3a) prostate cancer who had undergone brachytherapy, with or without EBRT and
      androgen deprivation therapy (ADT). Patients were diagnosed from 2004 through
      2009. Intermediate-risk patients with Gleason score <=3+4 and 1 intermediate-risk
      factor were considered favorable and all others unfavorable. We used
      multivariable Fine-Gray competing risks regression to study PCSM while adjusting
      for sociodemographic and clinical factors and ADT use. RESULTS: Overall, 50.3% of
      intermediate- and high-risk patients who received brachytherapy and EBRT did not
      have significantly improved PCSM compared with that of the patients who received
      brachytherapy alone (adjusted hazard ratio [AHR] 1.46, 95% confidence interval
      [CI] 0.69-3.11; P=.322; 5-year PCSM 2.4% vs 1.0%). This lack of benefit was seen
      among favorable intermediate-risk (AHR 2.66, 95% CI 0.93-7.62, P=.069; 5-year
      PCSM 1.3% vs 0.6%), unfavorable intermediate-risk (AHR 0.68, 95% CI 0.16-2.96,
      P=.612; 5-year PCSM 1.0% vs 1.2%), and high-risk (AHR 1.82, 95% CI 0.67-4.98,
      P=.242; 5-year PCSM 5.3% vs 2.1%) subgroups. CONCLUSIONS: These results suggest
      that certain patients with intermediate- or high-risk prostate cancer treated
      with brachytherapy might not benefit from the addition of EBRT. A randomized
      controlled trial of brachytherapy plus ADT with or without EBRT for unfavorable
      intermediate- and favorable high-risk organ-confined prostate cancer should be
      undertaken.

PMID- 29063855
TI  - Potential Role of the Quality Assurance Review Center Platform in Global
      Radiation Oncology.

PMID- 29063854
TI  - Prospective Study of Serial Imaging Comparing Fluorodeoxyglucose Positron
      Emission Tomography (PET) and Fluorothymidine PET During Radical Chemoradiation
      for Non-Small Cell Lung Cancer: Reduction of Detectable Proliferation Associated
      With Worse Survival.
AB  - PURPOSE: To investigate the associations between interim tumor responses on 18F
      fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and 18F
      fluorothymidine (18F-FLT) PET and patient outcomes, especially progression-free
      survival (PFS) and overall survival (OS), in non-small cell lung cancer (NSCLC)
      patients. METHODS AND MATERIALS: Patients with FDG-PET/computed tomography stage
      I-III NSCLC were prescribed concurrent chemotherapy and radiation therapy (60 Gy
      in 30 fractions). Scans were acquired at baseline (FDG-PET/computed tomography
      [FDGBL] for radiation therapy planning and FLT-PET [FLTBL]), week 2 (FDGwk2 and
      FLTwk2), and week 4 (FDGwk4 and FLTwk4) of chemoradiation therapy. Tumor
      responses were categorized as complete or partial responses or stable or
      progressive disease (SD, PD) using European Organization for Research and
      Treatment of Cancer criteria. Associations between response, OS, and PFS were
      analyzed with univariate Cox regressions and plotted using Kaplan-Meier curves.
      RESULTS: Between 2009 and 2013, 60 patients were recruited. Thirty-seven (62%)
      were male, and the median age was 66 years (range, 31-86 years). Two-year OS and
      PFS were 0.51 and 0.26, respectively. Unexpectedly, SD on FLTwk2 compared with
      complete response/partial response was associated with longer OS (hazard ratio
      [95% confidence interval] 2.01 [0.87-4.65], P=.082) and PFS (2.01 [0.92-4.36],
      P=.061). Weeks 2 and 4 FDG PET/CT were not significantly associated with
      survival. Study scans provided additional information to FDGBL in 21 patients
      (35%). Distant metastases detected in 3 patients on FLTBL and in 2 patients on
      FDG/FLTwk2 changed treatment intent from curative to palliative. Locoregional
      progression during radiation therapy was observed in 5 (8%) patients, prompting
      larger radiation therapy fields. CONCLUSIONS: Stable uptake of 18F-FLT at week 2
      was paradoxically associated with longer OS and PFS. This suggests that
      suppression of tumor cell proliferation may protect against radiation-induced
      tumor cell killing. Baseline FLT, FLTwk2, and FDGwk2 detected rapid distant and
      locoregional progression in 10 patients (17%), prompting changes in management.

PMID- 29063858
TI  - Some nematodes from freshwater fishes in central Africa.
AB  - Twenty species (sixteen adult and four larval) of parasitic nematodes belonging
      to the Ascaridoidea, Camallanoidea, Cosmocercoidea, Dioctophymatoidea,
      Habronematoidea, Oxyuroidea, Seuratoidea, and Thelazioidea were collected from
      freshwater fishes of the Congo River basin in the Democratic Republic of the
      Congo and the Central African Republic in 2008 and 2012, respectively. Based on
      light and scanning electron microscopical examination, many species are
      redescribed in detail. This material also contained four previously unknown
      species, Labeonema longispiculatum sp. n. from Synodontis acanthomias Boulenger,
      Gendria longispiculata sp. n. from Schilbe grenfelli (Boulenger), G. sanghaensis
      sp. n. from Schilbe marmoratus Boulenger, and Cucullanus congolensis sp. n. from
      Auchenoglanis occidentalis (Valenciennes). The new species L. longispiculatum is
      mainly characterised by conspicuously long (210-228 um) spicules, approximately
      twice as long as those in other congeners, the length (45-48 um) of the
      gubernaculum and the host family (Mochokidae), whereas G. longispiculata by very
      long (1.2 mm) spicules, the shape of the oesophagus and cephalic vesicle,
      distribution of postanal papillae and the host family (Schilbeidae). Main
      characteristic features of G. sanghaensis are the presence of a hexagonal oral
      aperture surrounded by lip-like structures, the posterior portion of the
      oesophagus moderately expanded, spicules and the gubernaculum 414-438 um and 54
      57 um long, respectively, deirids located at the level of the posterior end of
      the oesophagus and the absence of cervical alae. Cucullanus congolensis differs
      from congeneric species parasitising African freshwater and brackish-water fishes
      mainly in the absence of a ventral precloacal sucker and lateral preanal
      papillae, the presence of a large median precloacal papilla-like formation,
      spicules 480-489 um long and the location of the excretory pore in the region of
      the oesophago-intestinal junction. Chabaudus Inglis et Ogden, 1965 is considered
      a junior synonym of Gendria Baylis, 1930 and, consequently, species listed in the
      former genus are transferred to the latter as G. alaini (Alfonso-Roque, 1981)
      comb. n., G. chabaudi (Inglis et Ogden, 1965) comb. n., G. dehradunensis (Rizvi,
      Bursey et Maity, 2016) comb. n., G. thysi (Puylaert, 1970) comb. n. and G.
      williamsi (Puylaert, 1970) comb. n. The findings represent many new host and
      geographical records.

PMID- 29063857
TI  - Anti-tumour necrosis factor activity in saliva of various tick species and its
      appearance during the feeding period.
AB  - Tumour necrosis factor (TNF) plays a central role in the inflammatory process. In
      the skin, it contributes to immune containment of tick-transmitted pathogens like
      Borrelia burgdorferi. In the saliva of some tick species, active compounds are
      present that inhibit detection of TNF in specific ELISA. We compared the presence
      of anti-TNF activity in saliva or salivary gland extract from 11 tick species
      from the family Ixodidae and demonstrated it in genera Ixodes Latreille, 1795 and
      Haemaphysalis Koch, 1844. Analysis of anti-TNF activity in Ixodes ricinus
      (Linnaeus, 1758) saliva during the feeding period showed that it is present in
      the late, rapid phase of engorgement. Significance of anti-TNF activity for tick
      feeding and transmission of tick-borne pathogens is discussed.

PMID- 29063856
TI  - Does neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization
      improve survival in patients undergoing liver transplant for hepatocellular
      carcinoma?
AB  - PURPOSE: We aimed to compare the overall (OS) and disease-free survival (DFS) of
      patients undergoing orthotopic liver transplant (OLT) for hepatocellular
      carcinoma who did and did not have neoadjuvant doxorubicin drug-eluting bead
      transarterial chemoembolization (DEB-TACE). METHODS: This is a retrospective
      study of 94 patients with HCC transplanted between 2000 and 2014 in a single
      tertiary center. Pre- and postoperative features, DFS and OS were compared
      between patients who received pre-OLT DEB-TACE (n=34, DEB-TACE group) and those
      who did not (n=60, non-TACE group). Radiologic and histologic response to
      neoadjuvant treatment as well as its complications were also studied. RESULTS:
      There were no significant differences in post-transplantation DFS and OS rates
      between groups (5-year DFS: 70% in DEB-TACE group vs. 63% in non-TACE group, P =
      0.454; 5-year OS: 70% in DEB-TACE group vs. 65% in non-TACE group, P = 0.532).
      The DEB-TACE group had longer OLT waiting time compared with the non-TACE group
      (110 vs. 72 days; P = 0.01). On univariate and multivariate analyses, alpha
      fetoprotein (AFP) levels >500 ng/mL prior to OLT were associated with decreased
      OS and DFS regardless of neoadjuvant approach (hazard ratio of 6, P = 0.001 and
      5.5, P = 0.002, respectively). CONCLUSION: Patients who underwent neoadjuvant DEB
      TACE and OLT for hepatocellular carcinoma had no statistically different OS or
      DFS at 3 and 5 years from patients undergoing OLT alone.

PMID- 29063859
TI  - Meticulous plasma isolation is essential to avoid false low-level viraemia in
      Roche Cobas HIV-1 viral load assays.
AB  - BACKGROUND: Pre-analytical sample processing is often overlooked as a potential
      cause of inaccurate assay results. Here we demonstrate how plasma, extracted from
      standard EDTA-containing blood collection tubes, may contain traces of blood
      cells consequently resulting in a false low-level HIV-1 viral load when using
      Roche Cobas HIV-1 assays. METHODS: The presence of human DNA in Roche Cobas 4800
      RNA extracts and in RNA extracts from the Abbott HIV-1 RealTime assay was
      assessed by quantifying the human albumin gene by means of quantitative PCR. RNA
      was extracted from plasma samples before and after an additional centrifugation
      and tested for viral load and DNA contamination. The relation between total DNA
      content and viral load was defined. RESULTS: Elevated concentrations of genomic
      DNA were detected in 28 out of 100 Cobas 4800 extracts and were significantly
      more frequent in samples processed outside of the AIDS Reference Laboratory. An
      association between genomic DNA presence and spurious low-level viraemia results
      was demonstrated. Supplementary centrifugation of plasma before RNA extraction
      eliminated the contamination and the false viraemia. CONCLUSIONS: Plasma isolated
      from standard EDTA-containing blood collection tubes may contain traces of HIV
      DNA leading to false viral load results above the clinical cutoff. Supplementary
      centrifugation of plasma before viral load analysis may eliminate the occurrence
      of this spurious low-level viraemia.

PMID- 29063860
TI  - Characterization of HCV resistance from a 3-day monotherapy study of
      voxilaprevir, a novel pangenotypic NS3/4A protease inhibitor.
AB  - BACKGROUND: Voxilaprevir (VOX; GS-9857) is a pangenotypic HCV NS3/4A protease
      inhibitor (PI) with potent antiviral activity against HCV genotypes (GTs) 1-6 and
      improved coverage of GT1 NS3 resistance-associated substitutions (RAS) associated
      with other HCV PIs. In a 3-day Phase Ib monotherapy study in patients infected
      with HCV GT1a, 1b, 2, 3 and 4, VOX was well-tolerated and resulted in maximal
      mean viral load reduction >3 log10 IU/ml at the 100 mg dose across all genotypes
      evaluated. This report characterizes the HCV NS3 RAS in the study. METHODS: The
      NS3 gene was amplified and successfully deep sequenced using MiSeq for 66
      patients at baseline and 61 patients post-baseline using 15% and 1% assay
      cutoffs. RESULTS: With a 15% assay cutoff, pretreatment HCV NS3 RAS were present
      in the HCV of 38% (9/24) of patients with GT1a and 5% (1/19) with GT3a; there
      were no pretreatment NS3 RAS present in patients with GT1b (n=6), GT2 (n=7) or
      GT4 (n=4). In patients with and without pretreatment NS3 RAS, >=3.4 log10 mean
      maximal viral load reductions over 3 days of VOX administration were observed.
      The majority of patients did not have detectable treatment-emergent NS3 RAS and
      only 12% (7/53) and 26% (14/53) had emergent NS3 RAS using 15% and 1% cutoffs,
      respectively. No NS3 RAS were detected in patients with GT2 or GT4. A156T or
      A156V were the most prevalent emergent NS3 RAS in patients with GT1a or GT1b
      infection, but were not observed in patients with GT3 infection. CONCLUSIONS: The
      lack of selection of NS3 RAS in the majority of patients demonstrates a high
      resistance barrier for VOX. ClinicalTrails.gov identifier NCT02185794.

PMID- 29063861
TI  - Analysis of time-correlated single photon counting data: a comparative evaluation
      of deterministic and probabilistic approaches.
AB  - We review various methods for analysing time-resolved fluorescence data acquired
      using the time-correlated single photon counting method in an attempt to evaluate
      their benefits and limitations. We have applied these methods to both
      experimental and simulated data. The relative merits of using deterministic
      approaches, such as the commonly used iterative reconvolution method, and
      probabilistic approaches, such as the smoothed exponential series method, the
      maximum entropy method and recently proposed basis pursuit denoising (compressed
      sensing) method, are outlined. In particular, we show the value of using multiple
      methods to arrive at the most appropriate choice of model. We show that the use
      of probabilistic analysis methods can indicate whether a discrete component or
      distribution analysis provides the better representation of the data.

PMID- 29063862
TI  - Doping Effect on the Physical Properties of
      Ca<sub>10</sub>Pt<sub>3</sub>As<sub>8</sub>(Fe<sub>2</sub>As<sub>2</sub>)<sub>5</
      ub> Single Crystals.
AB  - Ca10Pt3As8(Fe2As2)5 is a unique parent compound for superconductivity, which
      consists of both semiconducting Pt3As8 and metallic FeAs layers. We report the
      observation of superconductivity induced via chemical doping in either Ca site
      using rare-earth (RE) elements (RE = La, Gd) or Fe site using Pt. The interlayer
      distance and the normal-state physical properties of the doped system change
      correspondingly. The coupled changes include (1) superconducting transition
      temperature T_c increases with increasing both doping concentration and
      interlayer distance, (2) our Tc value is higher than previously reported maximum
      value for Pt doping in the Fe site, (3) both the normal-state in-plane
      resistivity and out-of-plane resistivity change from non-metallic to metallic
      behavior with increasing doping concentration and Tc, and (4) the transverse in
      plane magnetoresistance (MRab) changes from linear-field dependence to quadratic
      behavior upon increasing Tc. For La-doped compound with the highest Tc (~35 K),
      upper critical fields ("H" _"c2" ^"ab" , "H" _"c2" ^"c" ), coherence lengths
      (xiab, xic), and in-plane penetration depth (lambdaab) are estimated. We discuss
      the relationship between chemical doping, interlayer distance, and physical
      properties in this system.

PMID- 29063863
TI  - Controlled preparation of M(Ag, Au)/TiO2 through sulfydryl-assisted method for
      enhanced photocatalysis.
AB  - Here a simple and effective method was explored to fabricate M/TiO2 (M = Ag, Au)
      composites, which required neither pre-treatment of TiO2 nor any additives as
      reducing agent. Using amorphous TiO2 spheres functionalized with SH groups as
      starting materials, the noble metallic ions (Ag, Au) can be adsorbed by TiO2 due
      to their special affinity with SH groups, which is beneficial to the uniform
      dispersion of metallic ions on the surface of TiO2. Then the adsorbed ions were
      reduced to form noble metal nanoparticles by heating process (95  degrees C)
      directly without additive as reduction agent. Meanwhile, the amorphous TiO2 was
      transformed into anatase phase during the heating process. Thus, the
      transformation of TiO2 along with the reduction of noble metallic ions (Ag, Au)
      was simultaneously carried out by heating. The XRD patterns proved the formation
      of anatase TiO2 after heating. The characterizations of XPS and TEM proved the
      formation of Ag and Au nanoparticles on the surface of TiO2. The element mapping
      indicated that Ag nanoparticles are dispersed uniformly on the surface of TiO2.
      The photocatalytic activity of the composites has been investigated by the
      degradation of methyl orange under visible light irradiation. The results showed
      that when Ag/TiO2 (2.8 wt%) was used as photocatalyst, about 98% of the MO
      molecules were degraded in 70 min.

PMID- 29063864
TI  - Structural control in porous/compact multilayer systems grown by magnetron
      sputtering.
AB  - In this work we analyze a phenomenon that takes place when growing magnetron
      sputtered porous/compact multilayer systems by alternating the oblique angle and
      the classical configuration geometries. We show that the compact layers develop
      numerous fissures rooted in the porous structures of the film below, in a
      phenomenon that amplifies when increasing the number of stacked layers. We
      demonstrate that these fissures emerge during growth due to the high roughness of
      the porous layers and the coarsening of a discontinuous interfacial region. To
      minimize this phenomenon, we have grown thin interlayers between porous and
      compact films under the impingement of energetic plasma ions, responsible for
      smoothing out the interfaces and inhibiting the formation of structural fissures.
      This method has been tested in practical situations for compact TiO2/porous SiO2
      multilayer systems, although it can be extrapolated to other materials and
      conditions.

PMID- 29063865
TI  - In situ preparation of Fe3O4 in a carbon hybrid of graphene nanoscrolls and
      carbon nanotubes as high performance anode material for lithium-ion batteries.
AB  - A new conductive carbon hybrid combining both reduced graphene nanoscrolls and
      carbon nanotubes (rGNSs-CNTs) is prepared, and used to host Fe3O4 nanoparticles
      through an in situ synthesis method. As an anode material for LIBs, the obtained
      Fe3O4@rGNSs-CNTs shows good electrochemical performance. At a current density of
      0.1 A g-1, the anode material shows a high reversible capacity of 1232.9 mAh g-1
      after 100 cycles. Even at a current density of 1 A g-1, it still achieves a high
      reversible capacity of 812.3 mAh g-1 after 200 cycles. Comparing with bare Fe3O4
      and Fe3O4/rGO composite anode materials without nanoscroll structure, Fe3O4@rGNSs
      CNTs shows much better rate capability with a reversible capacity of 605.0 and
      500.0 mAh g-1 at 3 and 5 A g-1, respectively. The excellent electrochemical
      performance of the Fe3O4@rGNSs-CNTs anode material can be ascribed to the hybrid
      structure of rGNSs-CNTs, and their strong interaction with Fe3O4 nanoparticles,
      which on one hand provides more pathways for lithium ions and electrons, on the
      other hand effectively relieves the volume change of Fe3O4 during the charge
      discharge process.

PMID- 29063866
TI  - Fabrication of water-dispersible single-walled carbon nanotube powder using N
      methylmorpholine N-oxide.
AB  - Dispersion of nanocarbon materials in liquid media, via solution processing such
      as spraying, printing, spinning, etc. is one of the prerequisites for practical
      applications. Here we report that water-dispersible single-walled carbon
      nanotubes (SWCNTs) were prepared through successive treatments with
      chlorosulfuric acid (CSA)/H2O2 and N-methylmorpholine N-oxide (NMO) monohydrate.
      The powder of the CSA/H2O2- and NMO-treated SWCNTs (N-SWCNTs) could be readily
      redispersed in water in concentrations as high as 1 g l-1 without requiring a
      dispersant. The mechanism responsible for the high dispersity of the N-SWCNT
      powder in polar solvents, including water, was elucidated based on the high
      polarity of the NMO molecule. In order to highlight the wide applicability of the
      N-SWCNTs, they were used successfully to prepare conducting thin films by spray
      coating plastic substrates with an aqueous hybrid solution containing the N
      SWCNTs and Ag nanowires (NWs). In addition, a flexible, large-area thin-film
      heater was prepared based on the N-SWCNT/AgNW hybrid film with a transmittance of
      93% and sheet resistance of 30 Omega sq-1.

PMID- 29063867
TI  - Highly reflective Er-doped ZnO thin-film coating for application in a UV optical
      ring resonator.
AB  - We achieved doping-induced optical variation in Erbium-doped ZnO (EZO) that may
      prove to be a promising material for use in optical ring resonators. EZO thin
      film samples were deposited on n-type Si substrate via the sol-gel spin-coating
      technique followed by annealing in air at 500  degrees C. The doping-induced
      morphological variations of the deposited thin film were characterized using x
      ray diffraction, ellipsometry, scanning electron microscopy and energy dispersive
      x-ray spectroscopy. Further, in order to establish the suitability of EZO for
      optical applications, detailed optical analysis was performed that exhibited that
      1 mol% Er-doped ZnO may prove to be suitable material. Finally, a ring resonator
      design has been proposed using 1 mol% EZO thin film. The proposed structure was
      simulated using the MODE tool by Lumerical solutions. The Eigenmode Solver has
      been used to simulate and calculate the effective refractive index, group
      velocity, propagation constant beta, dispersion and bending losses for a
      wavelength region of 200 nm to 900 nm. Simplified expressions for the free
      spectral range, full-width at half-maximum and quality factor have been derived
      and validated by the simulated data for the proposed ring resonator.

PMID- 29063868
TI  - Dual-gate operation and carrier transport in SiGe p-n junction nanowires.
AB  - We investigate carrier transport in silicon-germanium nanowires with an axial p-n
      junction doping profile by fabricating these wires into transistors that feature
      separate top gates over each doping segment. By independently biasing each gate,
      carrier concentrations in the n- and p-side of the wire can be modulated. For
      these devices, which were fabricated with nickel source-drain electrical
      contacts, holes are the dominant charge carrier, with more favorable hole
      injection occurring on the p-side contact. Channel current exhibits greater
      sensitivity to the n-side gate, and in the reverse biased source-drain
      configuration, current is limited by the nickel/n-side Schottky contact.

PMID- 29063870
TI  - Endoscopic ultrasound-guided pancreatic duct drainage: Ready for the prime time?

PMID- 29063869
TI  - Role of chemotherapy in prostate cancer.
AB  - Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes.
      While earlier studies utilized varying chemotherapy regimens which were found to
      be largely palliative in nature and hardly resulted in durable or meaningful
      responses, docetaxel resulted in the first chemotherapy agent that showed
      improvement in overall survival in metastatic castration-resistant prostate
      cancer (mCRPC). However, combination chemotherapy or any agents added to
      docetaxel have failed to yield incremental benefits. The improvement in overall
      survival as well as secondary endpoints of prostate-specific antigen (PSA) and
      time to recurrence when using docetaxel in the metastatic hormone-sensitive state
      has changed the standard of care for treatment of newly diagnosed de novo
      metastatic PCa. There are also promising results in locally advanced PCa and high
      risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes
      the historical as well as the more contemporary use of chemotherapeutic agents in
      PCa in varying states and phases of disease.

PMID- 29063871
TI  - A multi-institutional consensus on how to perform endoscopic ultrasound-guided
      peri-pancreatic fluid collection drainage and endoscopic necrosectomy.
AB  - There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst
      drainage and endoscopic necrosectomy should be performed. This survey was carried
      out amongst members of the EUS Journal Editorial Board to describe their
      practices in performing this procedure. This was a worldwide multi-institutional
      survey amongst members of the EUS Journal Editorial Board in May 2017. The
      responses to a 22-question survey with respect to the practice of EUS-guided
      pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two
      endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the
      opinion that lumen-apposing metal stents (LAMS) should be the standard of care
      for the creation of an endoscopic cystenterostomy in patients with pancreatic
      walled-off necrosis (WON); 95.5% (21/22) recommended large diameter (d=15 mm)
      LAMS for drainage in patients with WON; 54.5% (12/22) would not dilate LAMS after
      placement into the WOPN; 86.4% (19/22) would not perform endoscopic necrosectomy
      during the same procedure as the creation of the cystenterostomy; 45.5% (10/22)
      recommend that agents, such as diluted hydrogen peroxide, should be used to
      lavage the peri-pancreatic fluid collection (PFC) cavity in patients with WON;
      and 45.5% (10/22) considered a naso-cystic or other tube to be necessary for
      lavage of WON after initial drainage. The mean optimal interval recommended for
      endoscopic necrosectomy procedures after EUS-guided drainage was 6.23 days. The
      mean optimal interval recommended for repeat imaging in patients undergoing
      endoscopic necrosectomy was 12.32 days. The mean time recommended for LAMS
      removal was 4.59 weeks. This is the first worldwide survey on the practice of EUS
      guided pseudocyst drainage and endoscopic necrosectomy. There were wide
      variations in practice and randomized studies are urgently needed to establish
      the best approach for management of this condition. There is also a pressing need
      to establish a best practice consensus.

PMID- 29063872
TI  - Endobronchial ultrasonography using a guide sheath technique for diagnosis of
      peripheral pulmonary lesions.
AB  - Endobronchial ultrasonography using a guide sheath (EBUS-GS) is a novel method
      used for collecting peripheral pulmonary lesion (PPL) samples. EBUS-GS is
      performed by introducing a guide sheath-covered miniprobe into the target
      bronchus and then withdrawing the miniprobe after lesion detection, leaving the
      guide sheath in situ as a working channel for obtaining lesion samples. EBUS-GS
      can improve PPL diagnosis rates and be used for obtaining specimens for molecular
      analysis. In this review, we discuss the clinical applications of EBUS-GS, the
      factors that affect its diagnostic sensitivity, and potential complications. We
      also compare EBUS-GS with other available diagnostic techniques and discuss the
      strengths and limitations of this method.

PMID- 29063874
TI  - A rare case of pancreatic metastasis of angiosarcoma: Diagnosed by endoscopic
      ultrasound-guided fine-needle aspiration and biopsy.

PMID- 29063873
TI  - Future role of endoscopic ultrasound in personalized management of pancreatic
      cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is aggressive and lethal with the
      majority of cases presenting with advanced unresectable disease due to delayed
      diagnosis. Despite improvement in surgery, chemotherapies, and intensive care
      medicine, the outcome of PDAC remains poor, which may relate to the tumor
      biology. Recent data suggest that PDAC is a "systemic cancer" with complex
      molecular or genomics derangement with marked heterogeneity. The ability to
      characterize the PDAC better by detailed evaluation of tissue biomarkers or
      genomics allows for improved prediction of prognosis and stratification of
      treatment, a concept known as "personalized cancer therapy." Using tissue from
      resected PDAC specimens has several weaknesses and is only possible in 20% of
      patients with PDAC. Endoscopic ultrasound (EUS)-guided biopsy overcomes these
      weaknesses, and with recent advancements in needle technology, tissue can be
      obtained for personalized cancer therapy for all patients with PDAC. This review
      aims to outline our current understanding of the molecular biology of PDAC
      specifically focusing on how EUS-guided biopsy may play a fundamental role in
      tissue acquisition, allowing for assessment and stratify therapy according to the
      individual cancer biology as we move toward the era of precision medicine.

PMID- 29063875
TI  - Laboratory diagnosis of tuberculosis: Advances in technology and drug
      susceptibility testing.
AB  - There have been rapid technological advances in the detection of Mycobacterium
      tuberculosis and its drug susceptibility in clinical samples. These include
      advances in microscopic examination, in vitro culture and application of
      molecular techniques. The World Health Organization (WHO) has played a large role
      in evaluating these technologies for their efficacy and feasibility, especially
      in the developing countries. Amongst these, the Revised National Tuberculosis
      Control Programme (RNTCP), through its national network of designated microscopy
      centres and intermediate reference laboratories, has adopted certain technologies
      that are currently implemented in India. Advances in microscopy technology
      include fluorescent microscopy using light-emitting diode source, sodium
      hypochlorite microscopy and vital fluorescent staining of sputum smears.
      Automation of in vitro culture has markedly reduced the turnaround time (TAT),
      even in smear-negative samples, and permits simultaneous detection of resistant
      mutants. Molecular detection of drug resistance has further reduced the TAT, and
      the cartridge-based nucleic acid amplification test with its performance
      convenience and rapid results, appears poised to become the future of
      tuberculosis (TB) diagnosis in all settings, provided the cost of testing is
      reduced especially for use in private diagnostic settings. This article reviews
      technologies currently available for the diagnosis of TB, keeping in mind the WHO
      recommendations and the RNTCP practices. This is a thematic synthesis of data
      available on diagnosis in literature, preserving the conclusions of the primary
      studies.

PMID- 29063876
TI  - Prevalence of hepatitis B and hepatitis C virus co-infection in India: A
      systematic review and meta-analysis.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) have several important
      similarities including worldwide distribution, hepato-tropism, similar modes of
      transmission and the ability to induce chronic infection that may lead to liver
      cirrhosis and hepatocellular carcinoma. Since both viruses are individually known
      to cause the pathologies mentioned above, co-infection with both HBV and HCV
      would be expected to be linked with higher morbidity as well as mortality and
      impact healthcare resource utilisation. Precise estimate of the prevalence of
      HBV/HCV co-infection would be needed to formulate policy decisions and plan
      communal health interventions. This systematic review and meta-analysis,
      therefore, aims to understand the prevalence of HBV and HCV co-infection in India
      based on the available literature. Following PRISMA guidelines, primary studies
      reporting the prevalence of HBV/HCV co-infection in India were retrieved through
      searches conducted in PubMed, Google SCHOLAR, Medline, Cochrane Library, WHO
      reports, Indian and International journals online. All online searches were
      conducted between December 2016 and February 2017. Meta-analysis was carried out
      using StatsDirect statistical software. Thirty studies published between 2000 and
      2016 conducted across six regions of India were included in this review. The
      pooled HBV/HCV co-infection prevalence rate across the thirty studies was 1.89%
      (95% confidence intervals [CI] = 1.2%-2.4%). A high heterogeneity was observed
      between prevalence estimates. The HBV/HCV co-infection prevalence in different
      subgroups varied from 0.02% (95% CI = 0.0019%-0.090%) to 3.2% (95% CI = 1.3%
      5.9%). The pooled prevalence of HBV/HCV co-infection in India was found to be
      1.89%. This systematic review and meta-analysis revealed high prevalence of
      HBV/HCV co-infection in chronic liver patients, followed by HIV-positive
      patients, and then followed by persons who inject drugs and kidney disease
      patients.

PMID- 29063877
TI  - Optimisation of antimicrobial dosing based on pharmacokinetic and pharmacodynamic
      principles.
AB  - While suboptimal dosing of antimicrobials has been attributed to poorer clinical
      outcomes, clinical cure and mortality advantages have been demonstrated when
      target pharmacokinetic (PK) and pharmacodynamic (PD) indices for various classes
      of antimicrobials were achieved to maximise antibiotic activity. Dosing
      optimisation requires a good knowledge of PK/PD principles. This review serves to
      provide a foundation in PK/PD principles for the commonly prescribed antibiotics
      (beta-lactams, vancomycin, fluoroquinolones and aminoglycosides), as well as
      dosing considerations in special populations (critically ill and obese patients).
      PK principles determine whether an appropriate dose of antimicrobial reaches the
      intended pathogen(s). It involves the fundamental processes of absorption,
      distribution, metabolism and elimination, and is affected by the antimicrobial's
      physicochemical properties. Antimicrobial pharmacodynamics define the
      relationship between the drug concentration and its observed effect on the
      pathogen. The major indicator of the effect of the antibiotics is the minimum
      inhibitory concentration. The quantitative relationship between a PK and
      microbiological parameter is known as a PK/PD index, which describes the
      relationship between dose administered and the rate and extent of bacterial
      killing. Improvements in clinical outcomes have been observed when antimicrobial
      agents are dosed optimally to achieve their respective PK/PD targets. With the
      rising rates of antimicrobial resistance and a limited drug development pipeline,
      PK/PD concepts can foster more rational and individualised dosing regimens,
      improving outcomes while simultaneously limiting the toxicity of antimicrobials.

PMID- 29063878
TI  - Recurrent urinary tract infections in women: How promising is the use of
      probiotics?
AB  - Urinary tract infections (UTIs) currently rank amongst the most prevalent
      bacterial infections, representing a major health hazard. UTIs in females usually
      start as vaginal infections and ascend to the urethra and bladder. Recurrent UTIs
      (rUTIs) can be defined as at least three episodes of UTI in 1 year or two
      episodes in 6 months. Various antibiotics have been the mainstay of therapy in
      ameliorating the incidence of UTIs, but recurrent infections continue to afflict
      many women. It necessitates the exploitation of alternative antimicrobial
      therapy. Probiotics have been shown to be effective in varied clinical trials for
      long-term preventions of rUTI. Because Escherichia coli is the primary pathogen
      involved in UTIs which spreads from the rectum to vagina and then ascends up the
      sterile urinary tract, improving the gut or vaginal flora will thus impact the
      urinary tract. Since a healthy vaginal microbiota is mainly dominated by
      Lactobacillus species, in this context, exogenously administered probiotics
      containing Lactobacilli play a pivotal role in reducing the risk of rUTI. The
      concept of artificially boosting the Lactobacilli numbers through probiotic
      administration has long been conceived but has been recently shown to be
      possible. Lactobacilli may especially be useful for women with a history of
      recurrent, complicated UTIs or on prolonged antibiotic use. Probiotics do not
      cause antibiotic resistance and may offer other health benefits due to vaginal re
      colonisation with Lactobacilli. However, more comprehensive research is still
      needed, to recommend for probiotics as an alternative to antibiotics.

PMID- 29063879
TI  - Review on transovarial transmission potentiality of dengue vectors: An
      international perspective with special reference to North-Eastern region of
      India.
AB  - Despite extensive research in vaccine development, there is at present no known
      method of controlling dengue except by the mosquito vectors. Virologic
      surveillance which involves the detection of dengue virus (DENV) in human serum
      and followed by isolation of virus using cell culture or mosquito inoculation is
      used as an early warning symptom to predict the outbreak. The technique is not
      much effective as the virus is in the human population. However, if the virus is
      detected in mosquito before it can infect humans could be more effective
      approach. One of the great mysteries about the epidemiology of dengue is how the
      virus persists in the interepidemic period. So far, no such studies on dengue
      vectors have been conducted in the north-eastern region of India, especially in
      Assam and the dengue cases are increasing every year. There are no reports on the
      identification of active and potential role of dengue vector responsible for the
      transmission of dengue in this state. Such type of study will give an overall
      picture of potential dengue vector responsible for human DENV infection and the
      viral load carried by the mosquito species in different generations. Such study
      will be useful in helping the public health personnel.

PMID- 29063880
TI  - Discriminatory power of three typing techniques in determining relatedness of
      nosocomial Klebsiella pneumoniae isolates from a tertiary hospital in India.
AB  - PURPOSE: The purpose of this study was to evaluate the discriminatory power of
      two DNA-based technique and a protein-based technique for the typing of
      nosocomial isolates of Klebsiella pneumoniae. A second objective was to determine
      the antimicrobial susceptibility pattern and characterise the presence of genes
      encoding extended-spectrum beta-lactamases (ESBLs) and carbapenemases. MATERIALS
      AND METHODS: Forty-six K. pneumoniae isolates from patients with bloodstream
      infections at a tertiary care hospital in India between December 2014 and
      December 2015 were studied. All isolates were typed using enterobacterial
      repetitive intergenic consensus sequence-polymerase chain reaction (ERIC-PCR),
      randomly amplified polymorphic DNA (RAPD) analysis and matrix-assisted laser
      desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry. Antimicrobial
      susceptibility profiles and ESBLs were detected using the BD Phoenix system. The
      types of ESBL and carbapenemase genes present were detected using PCR. RESULTS:
      Isolates were subtyped into 31, 30 and 33 distinct genotypes by ERIC-PCR, RAPD
      and MALDI-TOF, respectively. Several isolates displaying identical DNA
      fingerprints were binned into different branches based on their proteomic
      fingerprint. Antimicrobial susceptibility tests revealed that 33/46 strains were
      multidrug resistant (MDR); a majority of the strains (83%) were sensitive to
      colistin. PCR-based analysis demonstrated 19 strains to harbour two or more ESBL
      and carbapenemase genes. CONCLUSION: ERIC-PCR was the most reproducible method
      for typing K. pneumoniae isolates and could not be substituted by MALDI-TOF for
      clonality analysis. A high degree of genetic diversity and the presence of MDR
      genes highlight the challenges in treating K. pneumoniae-associated infections.

PMID- 29063881
TI  - Antimicrobial prescribing patterns of surgical speciality in a tertiary care
      hospital in India: Role of persuasive intervention for changing antibiotic
      prescription behaviour.
AB  - BACKGROUND: Inappropriate use of antibiotics globally has been linked to increase
      in antibiotic resistance. OBJECTIVES: This interventional study assessed the
      impact of antibiotic prescription feedback and focus group discussions (FGD) on
      hospital-based prescribers before and after the FGD. STUDY DESIGN: The present
      study was performed at a tertiary care centre in New Delhi, wherein 45 units from
      surgical specialities were included for FGD. Thirty-five units were assessed for
      the antibiotic usage during 12 months pre-intervention and 3 and 6 months post
      intervention period. The outcome measured was a change in antibiotic prescription
      rates reflected as daily defined doses per 100 bed days as defined by the World
      Health Organisation. RESULTS: Reduction in the level of antibiotic consumption
      was observed in 15 of 35 units (42.85%) during the 3 months post-intervention
      period, which was significant (P < 0.05) in 3/35 (8.57%) surgical units. A
      significant reduction (P < 0.05) was observed for the units of endoscopic
      gynaecology, super-speciality and transplant surgery units B and C, and
      orthopaedic unit C during the 6 months period. Decreasing trend (P < 0.05) was
      observed in 2/35 (5.71%) units during the entire period. Overall reduction of
      antibiotic consumption (1.88%) was observed, with an increase in the use of low
      end antibiotics and a decrease in the use of high-end antibiotics. CONCLUSION:
      The present study clearly demonstrates a weak impact of FGD in changing
      antibiotic prescribing behaviour. Further analysis of the sustainability of FGD
      and its long-term impact on antimicrobial resistance needs to be evaluated. The
      effect of continuous educational sessions and multifaceted interventions cannot
      be ignored.

PMID- 29063882
TI  - Diagnostic efficacy of microscopy, rapid diagnostic test and polymerase chain
      reaction for malaria using bayesian latent class analysis.
AB  - INTRODUCTION: The diagnostic techniques for malaria are undergoing a change
      depending on the availability of newer diagnostics and annual parasite index of
      infection in a particular area. At the country level, guidelines are available
      for selection of diagnostic tests; however, at the local level, this decision is
      made based on malaria situation in the area. The tests are evaluated against the
      gold standard, and if that standard has limitations, it becomes difficult to
      compare other available tests. Bayesian latent class analysis computes its
      internal standard rather than using the conventional gold standard and helps
      comparison of various tests including the conventional gold standard. MATERIALS
      AND METHODS: In a cross-sectional study conducted in a tertiary care hospital
      setting, we have evaluated smear microscopy, rapid diagnostic test (RDT), and
      polymerase chain reaction (PCR) for diagnosis of malaria using Bayesian latent
      class analysis. RESULTS: We found the magnitude of malaria to be 17.7% (95%
      confidence interval: 12.5%-23.9%) among the study subjects. In the present study,
      the sensitivity of microscopy was 63%, but it had very high specificity (99.4%).
      Sensitivity and specificity of RDT and PCR were high with RDT having a marginally
      higher sensitivity (94% vs. 90%) and specificity (99% vs. 95%). On comparison of
      likelihood ratios (LRs), RDT had the highest LR for positive test result (175)
      and the lowest LR for negative test result (0.058) among the three tests.
      CONCLUSION: In settings like ours conventional smear microscopy may be replaced
      with RDT and as we move toward elimination and facilities become available PCR
      may be roped into detect cases with lower parasitaemia.

PMID- 29063883
TI  - Standardization of a two-step real-time polymerase chain reaction based method
      for species-specific detection of medically important Aspergillus species.
AB  - PURPOSE: Standardization of Aspergillus polymerase chain reaction (PCR) poses two
      technical challenges (a) standardization of DNA extraction, (b) optimization of
      PCR against various medically important Aspergillus species. Many cases of
      aspergillosis go undiagnosed because of relative insensitivity of conventional
      diagnostic methods such as microscopy, culture or antigen detection. The present
      study is an attempt to standardize real-time PCR assay for rapid sensitive and
      specific detection of Aspergillus DNA in EDTA whole blood. MATERIALS AND METHODS:
      Three nucleic acid extraction protocols were compared and a two-step real-time
      PCR assay was developed and validated following the recommendations of the
      European Aspergillus PCR Initiative in our setup. In the first PCR step (pan
      Aspergillus PCR), the target was 28S rDNA gene, whereas in the second step,
      species specific PCR the targets were beta-tubulin (for Aspergillus fumigatus,
      Aspergillus flavus, Aspergillus terreus), gene and calmodulin gene (for
      Aspergillus niger). RESULTS: Species specific identification of four medically
      important Aspergillus species, namely, A. fumigatus, A. flavus, A. niger and A.
      terreus were achieved by this PCR. Specificity of the PCR was tested against 34
      different DNA source including bacteria, virus, yeast, other Aspergillus sp.,
      other fungal species and for human DNA and had no false-positive reactions. The
      analytical sensitivity of the PCR was found to be 102 CFU/ml. CONCLUSION: The
      present protocol of two-step real-time PCR assays for genus- and species-specific
      identification for commonly isolated species in whole blood for diagnosis of
      invasive Aspergillus infections offers a rapid, sensitive and specific assay
      option and requires clinical validation at multiple centers.

PMID- 29063884
TI  - Molecular and phylogenetic evidence of chikungunya virus circulating in Assam,
      India.
AB  - PURPOSE: Northeast Region of India possesses an abundant number of Aedes
      mosquitoes, the common vector for Dengue and Chikungunya (CHIK). Dengue is
      reported every year from Assam, but active surveillance for CHIK virus (CHIKV)
      infection is lacking in this part of India. Therefore, this present study has
      been undertaken to detect any CHIKV infection during a dengue outbreak in Assam.
      MATERIALS AND METHODS: A total of 42 dengue negative samples collected from
      Guwahati were screened for the presence of CHIK IgM antibodies. Further, all the
      samples were processed for CHIKV RNA detection by reverse transcriptase
      polymerase chain reaction (RT-PCR). Phylogenetic analysis was done by Maximum
      Likelihood method using Kimura-2 parameter model. RESULTS: No IgM positivity was
      found in the processed samples; however, 7 samples were positive for CHIKV by RT
      PCR. Phylogenetic analysis revealed that the circulating CHIKV belonged to
      Eastern, Central and Southern African genotype. Sequence analysis showed two
      uniform nucleotide substitutions and very less amino acid substitution.
      CONCLUSION: Silent existence of CHIKV beside dengue is reported from this study.
      Therefore, CHIKV diagnosis should be included as a regular practice for active
      surveillance of the disease and its accomplishment before commencing an outbreak.

PMID- 29063885
TI  - Systemic antibody response to Chlamydia Trachomatis infection in patients either
      infected or reinfected with different Chlamydia serovars.
AB  - INTRODUCTION: Chlamydia trachomatis is the etiological agent for the most
      prevalent bacterial sexually transmitted infection in both developed and
      developing countries. The aim of present study was to characterize the antibody
      response between two groups of individuals, having either a single C. trachomatis
      infection and or repeated infections. MATERIAL AND METHODS: Current study
      consisted of two groups, one with an initial Chlamydia infection and a second
      with repeated infections. A titre based estimation of specific serum (IgG and
      IgA) levels using ELISA were performed, which further validated by western blot.
      In vitro neutralizing ability of each patient's serum against both homologous and
      heterologous strains was also determined. RESULTS: Individuals infected with one
      of the C. trachomatis serovars D, E or K exhibited a strong systemic antibody
      response as characterized by ELISA and western blot. These individuals may have
      developed at least some level of protection as they only represented single
      infection. By comparison, individuals infected with serovar D, E or F that
      exhibited low systemic antibody response often presented repeated C. trachomatis
      infections, suggesting an association with poor immune response. An in vitro
      neutralizing level of 60-90% was observed in the human sera against homologous
      serovar D and two heterologous C. trachomatis serovars E and K, compared to <40%
      against heterologous serovars F. CONCLUSION: Individuals infected with serovars D
      and K showed a potential association between circulating antibody response and re
      infection risk. While the patients infected with serovars E showed a
      disconnection between systemic antibody response and re-infection risk.

PMID- 29063886
TI  - Evaluation of concurrent malaria and dengue infections among febrile patients.
AB  - CONTEXT: Despite a wide overlap between endemic areas for two important vector
      borne infections, malaria and dengue, published reports of co-infections are
      scarce till date. AIMS: To find the incidence of dengue and malaria co-infection
      as well as to ascertain the severity of such dengue and malaria co-infection
      based on clinical and haematological parameters. SETTING AND DESIGN:
      Observational, retrospective cross-sectional study was designed including
      patients who consulted the tertiary care hospital of Ahmedabad seeking treatment
      for fever compatible with malaria and/or dengue. SUBJECTS AND METHODS: A total of
      8364 serum samples from clinically suspected cases of fever compatible with
      malaria and/or dengue were collected. All samples were tested for dengue NS-1
      antigen before 5 days of onset of illness and for dengue IgM after 5 days of
      onset of illness. In all samples, malaria diagnosis was based on the
      identification of Plasmodium parasites on a thin and thick blood films
      microscopy. RESULTS: Only 10.27% (859) patients with fever were tested positive
      for dengue and 5.1% (434) were tested positive for malaria. 3.14% (27) dengue
      cases show concurrent infection with malarial parasites. Hepatomegaly and
      jaundice 37.03% (10), haemorrhagic manifestations 18.51% (5) and kidney failure
      3.7% (1), haemoglobin <12 g/dl 100% (27) and thrombocytopenia (platelet count
      <150,000/cmm) 96.29% (26) were common in malaria and dengue co-infections and
      were much more common in Plasmodium falciparum infections. CONCLUSION: All
      febrile patients must be tested for malaria and dengue, both otherwise one of
      them will be missed in case of concurrent infections which could lead to severe
      diseases with complications.

PMID- 29063888
TI  - Epidemiology of malaria and MSP-2 gene-based genetic diversity of Plasmodium
      falciparum from patients attending community health centre, Jiribam, Manipur.
AB  - Two millilitres of peripheral blood was collected from 323 patients of different
      age groups and rapid diagnosis (RDT test) was performed. Parasite genomic DNA was
      extracted from whole blood and MSP-2 gene-based diversity and polymorphism was
      determined followed by restriction fragment length polymorphism analysis using
      Taq 1 and Vsp 1 digestion of each polymerase chain reaction product to analyse
      MSP-2 genotypes. Twenty-six sequences of P. falciparum MSP-2 gene were retrieved
      from the current GenBank database to represent strains from various geographical
      locations and were analysed for the Taq 1 and Vsp 1 enzyme restriction sites
      using in silico restriction digestion in Sequence Manipulation Suite, Version 2.

PMID- 29063887
TI  - Detection of clarithromycin-resistant Helicobacter pylori by polymerase chain
      reaction using residual samples from rapid urease test.
AB  - BACKGROUND: Approximately 50% of the world population is infected with
      Helicobacter pylori, which corresponds to a high infection rate. Furthermore, the
      incidence of antibiotic-resistant H. pylori has increased with the recent rise in
      use of antibiotics for H. pylori elimination, suggesting growing treatment
      failures. AIM: The study was aimed to assess the use of residual samples from
      rapid urease test (RUT) for biomolecular testing as an effective and accurate
      method to detect antibiotic-resistant H. pylori. SETTINGS AND DESIGN: This study
      was a retrospective study performed using data obtained from medical records of
      previously isolated H. pylori strains. MATERIALS AND METHODS: RUT was conducted
      for 5440 biopsy samples from individuals who underwent health examination in
      South Korea. Subsequently, 469 RUT residual samples were randomly selected and
      subjected to polymerase chain reaction (PCR) to detect antibiotic-resistant H.
      pylori. STATISTICAL ANALYSIS USED: The Chi-square test was used to analyse
      categorical data. P < 0.05 was considered statistically significant. RESULTS: The
      results showed a concordance between the results of PCR and conventional RUT in
      450 of 469 samples, suggesting that the H. pylori PCR test is a time- and cost
      effective detection method. CONCLUSIONS: This study demonstrated that PCR test
      can aid physicians to prescribe the appropriate antibiotics at the time of
      diagnosis, thus preventing the reduction in H. pylori eradication due to
      antibiotic resistance, averting progression to serious diseases and increasing
      the treatment success rate.

PMID- 29063889
TI  - Survivability and fitness cost of heterogeneous vancomycin-intermediate
      Staphylococcus aureus.
AB  - The aim of this study was to observe the survivability and fitness cost of
      heterogeneous vancomycin-intermediate Staphylococcus aureus(hVISA) isolates.
      Survivability study was performed on dry cotton swab, and fitness cost was
      evaluated by estimating growth kinetics and generation time constant in BACTEC
      automated system. Total mean maximum time of recovery on primary culture was 4.1
      and 7.1 weeks (P = 0.0001) for hVISA and vancomycin-sensitive S. aureus (VSSA),
      respectively, in dry starved condition. No significant difference between the
      mean value of lag phase duration (P = 0.89) was noted between hVISA and VSSA
      isolate in growth kinetics. However, we observed lesser generation time of hVISA
      isolates compared to S. aureus ATCC 29213 (P = 0.0076). This study concluded that
      a significant difference in generation time between VSSA and hVISA and suggests
      that hVISA have fitness cost compared to VSSA. However, further studies with more
      cases are required.

PMID- 29063890
TI  - Investigation of an outbreak of varicella in Chandigarh, North India, using a
      real-time polymerase chain reaction approach.
AB  - Outbreaks of varicella are reported when susceptible population accumulates. This
      study reports a chickenpox outbreak in Burail in August 2014, wherein 20
      laboratory-confirmed cases were identified by the detection of varicella zoster
      virus (VZV) DNA and VZV IgM antibodies. The viral load between vesicular swabs
      and serum samples from 8 patients with active lesions was found to have good
      correlation and further also related with disease severity. Real-time polymerase
      chain reaction can be useful for early diagnosis of an outbreak and vesicular
      swab can be used as a less invasive sample for assessing the disease severity.

PMID- 29063891
TI  - Identification of carbapenemase-mediated resistance among Enterobacteriaceae
      bloodstream isolates: A molecular study from India.
AB  - Acquired resistance in carbapenem-resistant Enterobacteriaceae (CRE) conferred by
      carbapenemases is a major concern worldwide. Consecutive, non-duplicate isolates
      of Escherichia coli (EC) and Klebsiella pneumoniae from clinically diagnosed
      bloodstream infections were screened for the presence of carbapenem resistance by
      standard disk-diffusion method and minimum inhibitory concentration breakpoints
      using the Clinical and Laboratory Standards Institute guidelines. Carbapenemase
      encoding genes were amplified by polymerase chain reaction. Of 387 isolates (214
      K. pneumoniae, 173 EC) tested, 93 (24.03%) were found to be CRE. Of these, 71
      (76.3%) were positive for at least one tested carbapenemase gene. The frequency
      of carbapenemase genes was New Delhi metallo-beta-lactamse-1 (65.6%),
      oxacillinase (OXA)-48 (24.7%), OXA-181 (23.6%), Verona integron-encoded metallo
      beta-lactamase (6.4%) and K. pneumoniae carbapenemase (2.1%). Our study
      identified presence of carbapenemases in a large proportion of CRE isolates.
      Delineation of resistance mechanisms is important in view of future therapeutics
      concerned with the treatment of CRE and for aiding control efforts by
      surveillance and infection control interventions.

PMID- 29063892
TI  - Hantavirus and tuberculosis co-infection in an Indian child.
AB  - Hantaviruses are a group of antigenically distinct viruses carried out in rodents
      and insectivores. Humans are accidental hosts and get infected by aerosols
      generated from contaminated urine, faeces and saliva of infected rodents.
      Hantaviruses are identified as aetiological agents of two human diseases,
      haemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.
      Hantavirus causing pulmonary renal disease has rarely been reported in children
      in India. Hantavirus infection is uncommon under the age of 12 years. We report a
      9-year-old girl from Mumbai, India with fever, bilateral pleural effusion,
      thrombocytopaenia, haemoconcentration and oliguria due to hantavirus infection.
      She also had associated tuberculosis.

PMID- 29063893
TI  - A case of sterile pyuria caused by Chlamydia trachomatis and Mycoplasma hominis:
      A diagnostic challenge.
AB  - Sterile pyuria is a highly prevalent condition with a wide aetiological spectrum,
      which often challenges the diagnostician. We describe the case of a middle-aged
      female admitted to the medical Intensive Care Unit for acute gastroenteritis,
      whose urinalysis revealed persistent sterile pyuria. Polymerase chain reaction
      assay in urine was positive for Chlamydia trachomatis and Mycoplasma hominis. She
      responded to antimicrobial therapy. We hereby reflect on the approach to a case
      of sterile pyuria and review the available literature on this entity.

PMID- 29063894
TI  - Multiple parasitic and viral infections in a patient living with HIV/AIDS on
      antiretroviral therapy.
AB  - Patients with human immunodeficiency virus (HIV) infection are more prone for
      gastrointestinal infections causing diarrhoea, particularly with parasites.
      Parasitic infections have been regularly reported in such patients. A female
      patient confirmed positive for HIV 1 on antiretroviral therapy came with
      complaints of chronic diarrhoea for the past 7 months. Her initial CD4 count was
      89 cells/MUl of blood, and antibodies to cytomegalovirus and herpes simplex virus
      1 and 2 virus were found to be positive in the patient's serum, but there was no
      HIV-associated retinopathy. Her stool examination showed decorticated fertilised
      eggs of Ascaris lumbricoides, cysts of Blastocystis sp. and Entamoeba species in
      the unconcentrated sample and oocysts of Cystoisospora species, egg of
      Schistosoma haematobium and eggs of Trichuris trichiura in the concentrated. The
      patient responded well to cotrimoxazole and albendazole, and repeat samples were
      negative for all these parasites.

PMID- 29063895
TI  - Multidrug-resistant Candida auris: Need for alert among microbiologists.

PMID- 29063896
TI  - In vitro fosfomycin susceptibility against carbapenem-resistant or extended
      spectrum beta-lactamase-producing gram-negative fosfomycin-naive uropathogens: An
      alluring option or an illusion.

PMID- 29063897
TI  - Urbanization, cities, and health: The challenges to Nigeria - A review.
AB  - The Nigerian society is rapidly becoming urban as a result of a multitude of push
      and pull factors. This has generated urban health crises among city dwellers
      notably the urban poor. A systematic search of published literature in English
      was conducted between 1960 and 2015. Published peer review journals, abstracts,
      Gray literature (technical reports, government documents, reports, etc.),
      inaugural lectures, and internet articles were reviewed. Manual search of
      reference lists of selected articles were checked for further relevant studies.
      The review showed that the pace of urbanization is unprecedented with cities such
      as Lagos having annual urban growth rate of 5.8%. Urbanization in Nigeria is
      mainly demographically driven without commensurate socioeconomic dividends and
      benefits to the urban environment. This has created urban health crises of
      inadequate water safe supply, squalor and shanty settlements, sanitation, solid
      waste management, double burden of diseases and inefficient, congested, and risky
      transport system. In conclusion, when managed carefully, urbanization could
      reduce hardship and human suffering; on the other hand, it could also increase
      poverty and squalor. Some laws need to be amended to change the status of poor
      urban settlements. Urban health development requires intersectoral approach with
      political will and urban renewal program to make our urban societies sustainable
      that promote healthy living.

PMID- 29063898
TI  - Pattern of presentation of gastroesophageal reflux disease among patients with
      dyspepsia in Kano, Nigeria.
AB  - BACKGROUND: Dyspepsia is a symptom complex rather than a specific disease entity.
      It can be caused by both organic and functional gastrointestinal (GI) disorders.
      Gastroesophageal reflux disease (GORD) though a common digestive disorder
      worldwide is scarcely reported in Nigeria. The aim of this study is to determine
      the pattern of presentation of GORD among patients with dyspepsia. METHODS: One
      hundred and seventy dyspeptic patients were recruited consecutively as they were
      referred to the Gastroenterology Unit of Aminu Kano Teaching Hospital for upper
      GI endoscopy. A prepared questionnaire on relevant demographic and clinical
      history relating to GORD was administered. Upper GI endoscopy was then performed
      on each patient. RESULTS: The prevalence of GORD was 24.1%, with a M:F ratio of
      1:1.1. Endoscopy-positive variant accounted for 16 cases (9.4%), while endoscopy
      negative variant accounted for 25 cases (14.7%), with of the total GORD patients,
      26(63.4%) were males while 15(36.6%) were females. Los Angeles Grade A (37.5%)
      was the predominant endoscopic esophageal mucosal injury found in 6 cases.
      Barrett's esophagus and esophageal adenocarcinoma accounted 4.9% each and were
      considered to be rare. Extra-esophageal manifestations were also rare.
      CONCLUSIONS: Endoscopy-negative variant still remains the predominant endoscopic
      finding in GORD patients.

PMID- 29063899
TI  - Clinicians-related determinants of anticoagulation therapy and prophylaxis in
      Nigeria.
AB  - BACKGROUND: Thromboembolic and hypercoagulable diseases are common life
      threatening but treatable problems in hospital practice. Fortunately,
      anticoagulation is an efficacious management practice indicated for arterial,
      venous, and intracardiac thromboembolism. Clinicians in developing countries may
      have gaps in their knowledge of anticoagulation therapy/prophylaxis which could
      affect their clinical decision. OBJECTIVES: The study examined the knowledge and
      attitude of clinicians to anticoagulation therapy/prophylaxis in some tertiary
      hospitals in Nigeria. METHODOLOGY: The study was a multicenter survey. A
      pretested questionnaire was administered to clinicians in six tertiary hospitals
      in Southeast Nigeria. RESULTS: A total of 528 questionnaires were returned by 419
      (79.4%) residents and 109 (20.6%) consultants. We observed significant abysmal
      knowledge and lack of awareness of direct oral anticoagulants (DOACs) among most
      respondents irrespective of their job grades (P = 0.02, odds ratio [OR] 0.59, 95%
      confidence interval [CI] 0.38-0.90). Their knowledge of anti-Xa assay as
      laboratory monitoring tool was also significantly inadequate (P = 0.001, OR 0.23,
      95% CI 0.10-0.51). On statement analysis on their attitude to anticoagulation
      therapy/prophylaxis, "Do you think anticoagulation therapy/prophylaxis is
      clinically relevant" had the highest mean of 4.60, P = 0.01, and a high degree of
      agreement; while "Should hospital inpatient with > 3 days admission routinely
      receive anticoagulation/prophylaxis?" had the lowest mean of 2.27, P = 0.02, and
      a low degree of agreement. CONCLUSION: There is the need to upscale knowledge of
      anticoagulation agents and an attitude change to anticoagulation
      therapy/prophylaxis, especially on the DOACs through continuing medical education
      activities in emerging countries such as Nigeria.

PMID- 29063900
TI  - Demographic characteristics and visual status of patients undergoing cataract
      surgery at a tertiary hospital in Kano, Nigeria.
AB  - : Objective/Purpose: To describe the demographic and baseline ocular
      characteristics, prevalence of blindness and visual impairment among patients
      undergoing extracapsular cataract extraction for age related cataract at the
      study hospital over a one year period. Materials/Patients: All consecutive
      patients aged 40 years and above identified with age related cataract in one or
      both eyes who voluntarily agree to participate were included. METHODS: The study
      adhered to the tenets of the Helsinki declaration. Written informed consent was
      obtained from all eligible patients. All patients underwent basic eye examination
      by the ophthalmologist. Visual impairment was determined for each eye according
      to the standard WHO categorizations. Information obtained also included age, sex
      and history of previous cataract surgery. Data were recorded in manual tally
      sheets and on modified computer Cataract Surgery Record forms. Analyses were done
      using SPSS (version 16, SPSS Inc., Chicago, USA). RESULTS: The participation rate
      was 91.2%. There were 495 eyes of 487 consecutive patients. This include 212
      males and 275 females (M:F, 1:1.3). The age range was 40 to 99 years with a mean
      age of 62.76 +/- 10.49 years (61.35 +/- 9.75 years in men and 63.85+/-10.9 years
      in females). Most of the patients (n = 451; 92.6%, 95% CI: 89.9-94.6%) were aged
      50 years and above. Sixty patients (12.3%, 95% CI: 9.6-15.5%) had cataract in
      both eyes, 427 (87.7%, 95% CI: 84.5-90.3%) were in one eye. Among these,
      preoperatively 16 (3.3%, 95% CI: 2.0-5.3%) had aphakia, 21 (4.3%, 95% CI: 2.8
      6.5%) had uniocular pseudophakia. About 63.2% (95% CI: 58.9-67.4%) of patients
      had normal vision in the better eye (presenting VA >=6/18). Overall 9.5% (95% CI:
      7.3-12.7%) were bilaterally blind. About 96.8% of eyes (95% CI: 94.5-98.0%)
      undergoing cataract surgery were blind (presenting VAConclusion: The study
      highlights preponderance of females and high incidence of blinding cataract.
      Education and early disease awareness may play an important role in these
      patients and could improve cataract surgical services in our hospital..

PMID- 29063901
TI  - Eclampsia in rural Nigeria: The unmitigating catastrophe.
AB  - INTRODUCTION: Eclampsia is one of the most dreaded causes of adverse outcomes of
      pregnancy worldwide. It is one of the greatest causes of maternal and perinatal
      morbidity and mortality world over. We do not know the prevalence, management
      outcome, and the devastation caused by this dreaded disease in our center hence
      the need for this work. MATERIALS AND METHODS: This is a 7-year retrospective
      review of all cases of eclampsia managed in Mater Misericordiae Hospital Afikpo,
      a rural secondary cum referral Catholic Mission Hospital in Afikpo, Ebonyi State
      in Southeastern Nigeria. RESULTS: The prevalence of eclampsia in our center is
      1.12% or one case of eclampsia for every 89 women that delivered in our facility.
      The majority of the women that had eclampsia in our center 56 (71.8%) were
      primigravidae. Seventeen women (21.8%) had various antenatal complications with 4
      or 23.6% presenting with intrauterine fetal deaths and two (11.8%) each with
      intrauterine growth restriction, and domestic violence, respectively. Thirty-five
      or 44.9% of the women were delivered by emergency lower segment cesarean section.
      Fifteen or 17.9% babies were dead giving a perinatal mortality rate of 174 per
      1,000After delivery, and 3 (3.8%) of the women had postpartum hemorrhage. Two
      women (2.6%) died giving a maternal mortality ratio of 2564 per 100,000
      deliveries. CONCLUSION: Eclampsia is a dreaded obstetric disease with adverse
      fetal and maternal consequences that are not mitigating, and no effort should be
      spared in managing it effectively including public enlightenment.

PMID- 29063902
TI  - Tumor-associated macrophages, angiogenesis, and tumor cell migration in oral
      squamous cell carcinoma.
AB  - OBJECTIVE: To investigate the relationship between tumor-associated macrophages
      (TAMs), neovascularization, and tumor cell migration in oral squamous cell
      carcinoma (OSCC) of an African subpopulation. MATERIALS AND METHODS: Twenty OSCC
      paraffin blocks underwent immunohistochemistry to TAM1 (CCR7), TAM2 (CD206),
      Twist, E-cadherin, N-cadherin, and CD34. The relative percentage of CCR7 + and
      CD206 + cells to overall immune cell population was calculated for three high
      power fields and an average was taken. TAM-related microvessel density (MVD) was
      determined as the mean of the three recorded values. Cases that had no CD34 +
      vessels adjacent to the TAMs region were regarded as having an MVD score of 0.
      RESULTS: Ten cases (50%) expressed greater CCR7 activity than CD206, seven cases
      (35%) expressed approximately equal activity of CCR7 and CD206, while three cases
      (15%) expressed greater activity of CD206 than CCR7. Twist expression was strong
      in some cases with strong N-cadherin and weak E-cadherin, but the expression of
      Twist was not consistently high in all cases that expressed strong N-cadherin and
      weak E-cadherin. CONCLUSIONS: TAMs distribution suggested antitumor activity and
      the potential for tumor metastasis was only partly due to Twist-mediated
      epithelial-mesenchymal transition.

PMID- 29063903
TI  - Iron and vitamin D levels among autism spectrum disorders children.
AB  - AIM: The aim of this study was to investigate iron deficiency anemia and Vitamin
      D deficiency among autism children and to assess the importance of risk factors
      (determinants). SUBJECTS AND METHODS: This was a case-control study conducted
      among children suffering from autism at the Hamad Medical Corporation in Qatar. A
      total of 308 cases and equal number of controls were enrolled. The Autism
      Diagnostic Observation Schedule-Generic was the instrument used for diagnosis of
      Autism. RESULTS: The mean age (+/-standard deviation, in years) for autistic
      versus control children was 5.39 +/- 1.66 versus 5.62 +/- 1.81, respectively. The
      mean value of serum iron levels in autistic children was severely reduced and
      significantly lower than in control children (74.13 +/- 21.61 MUg/dL with a
      median 74 in autistic children 87.59 +/- 23.36 MUg/dL in controls) (P = 0.003).
      Similarly, the study revealed that Vitamin D deficiency was considerably more
      common among autistic children (18.79 +/- 8.35 ng/mL) as compared to healthy
      children (22.18 +/- 9.00 ng/mL) (P = 0.004). Finally, mean values of hemoglobin,
      ferritin, magnesium; potassium, calcium; phosphorous; glucose, alkaline
      phosphate, hematocrit, white blood cell, and mean corpuscular volume were all
      statistically significantly higher in healthy control children as compared to
      autistic children (P < 0.001). Multivariate logistic regression analysis revealed
      that serum iron deficiency, serum calcium levels, serum Vitamin D levels;
      ferritin, reduced physical activity; child order, body mass index percentiles,
      and parental consanguinity can all be considered strong predictors and major
      factors associated with autism spectrum disorders. CONCLUSION: This study
      suggests that deficiency of iron and Vitamin D as well as anemia were more common
      in autistic compared to control children.

PMID- 29063904
TI  - Study of carotid intimal medial thickness in essential hypertension with or
      without left ventricular hypertrophy.
AB  - INTRODUCTION: Hypertension and atherosclerosis though separate entities, are
      interrelated as hypertension plays an important role in the pathogenesis of
      atherosclerosis. This study was undertaken to study the association of carotid
      intimal medial thickness with left ventricular hypertrophy (LVH) in hypertensive
      patients. MATERIALS AND METHODS: Hundred hypertensives (JNC-7, Stage 1 and 2)
      between 30 and 55 years were enrolled in this prospective observational study
      conducted at a tertiary care teaching institute of Punjab, India.
      Electrocardiogram, Carotid Doppler, and Echocardiography were carried out in
      addition to routine biochemical investigations. RESULTS: Increased carotid
      intimal medial thickness (CIMT) had statistically significant association with
      age, duration of hypertension, high systolic and diastolic blood pressure (BP),
      left ventricular hypertrophy and left ventricular mass index but was not
      associated with body mass index, low-density lipoproteins, and total cholesterol.
      CONCLUSIONS: LVH and arterial wall changes occur concurrently, and therefore,
      management of hypertension should not be limited just to control of BP but should
      also include therapy for carotid plaques and increased CIMT.

PMID- 29063905
TI  - A rare case of bleeding disorder: Glanzmann's thrombasthenia.
AB  - BACKGROUND: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder, which is
      characterized by a lack of platelet aggregation. It is characterized by
      qualitative or quantitative abnormalities of the platelet membrane glycoprotein
      IIb/IIIa. Physiologically, this platelet receptor normally binds several adhesive
      plasma proteins, and this facilitates attachment and aggregation of platelets to
      ensure thrombus formation at sites of vascular injury. The lack of resultant
      platelet aggregation in GT leads to mucocutaneous bleeding whose manifestation
      may be clinically variable, ranging from easy bruising to severe and potentially
      life-threatening hemorrhages. OBJECTIVE: To highlight this rare but potentially
      life-threating disorder, GT. CASE REPORT: We report a case of GT that was first
      detected because of the multiple episodes of gum bleeding. The patient was an 18
      year-old girl who presented with a history of repeated episodes of gum bleeding
      since childhood. Till the first visit to our hospital, she had not been diagnosed
      with GT despite a history of bleeding tendency, notably purpura in areas of easy
      bruising, gum bleeding, and prolonged bleeding time after abrasions and insect
      stings. GT was diagnosed on the basis of prolonged bleeding time, lack of
      platelet aggregation with adenosine di phosphate, epinephrine and collagen.
      CONCLUSION: GT should always be considered as differential diagnosis while
      evaluating any case of bleeding disorder.

PMID- 29063906
TI  - Dual-energy computed tomographic visualization of urate crystals in a case of
      familial gout in Western India.

PMID- 29063909
TI  - Prevalence of carpal tunnel syndrome and its correlation with pain amongst female
      hairdressers.
AB  - OBJECTIVES: Carpal tunnel syndrome (CTS) may develop with repetitive and forced
      movements of the hands and wrists. In this study, we have aimed to evaluate
      whether the frequency of CTS is increased amongst female hairdressers as compared
      with unemployed women or not. Besides, we have also analyzed whether the
      functionality and pain intensity levels amongst female hairdressers with CTS are
      different from the ones of unemployed women with CTS or not. MATERIAL AND
      METHODS: The consecutive female hairdressers and unemployed women who had
      referred to our electroneuromyography (ENMG) laboratory for the upper extremity
      nerve conduction studies were included. They were evaluated in terms of clinical
      and ENMG findings, socio-demographic characteristics, functionality and pain
      intensity levels determined with the Boston CTS Questionnaire and visual analog
      scale (VAS). RESULTS: In this study, 110 women (70 female hairdressers and 40
      unemployed women) were included. The frequency of CTS among hairdressers (74.3%)
      was higher than the one of the unemployed control group (55%) (p = 0.032). We
      detected that as the time period of occupation in hairdressing increased, the
      risk of developing CTS also increased among hairdressers (p < 0.001).
      Additionally, pain intensity and functional loss levels were higher for
      hairdressers with CTS than those for the control group with CTS (p = 0.005, p <
      0.001, p = 0.028, respectively). CONCLUSIONS: The frequency of CTS is elevated
      for female hairdressers with respect to the unemployed women as in many other
      occupations requiring forced or repetitive hand movements. Besides, the
      occupational exposure in hairdressing also results in more elevated pain
      intensity and functional loss levels related with CTS as compared with the
      unemployed subjects. Int J Occup Med Environ Health 2018;31(3):333-339.

PMID- 29063908
TI  - Adherence to Mediterranean Diet and Non-Alcoholic Fatty Liver Disease: Effect on
      Insulin Resistance.
AB  - OBJECTIVES: The prevalence of cardiometabolic disorders, including non-alcoholic
      fatty liver disease (NAFLD), is increasing in western countries, because of
      changes in lifestyle and dietary habits. Mediterranean Diet (Med-Diet) is
      effective for cardiovascular prevention, but its relationship with NAFLD has been
      scarcely investigated. METHODS: We included 584 consecutive outpatients
      presenting with one or more cardiovascular risk factor such as type 2 diabetes
      mellitus (T2DM), arterial hypertension, overweight/obesity, and dyslipidemia.
      Liver steatosis was assessed using ultrasonography. Med-Diet adherence was
      investigated by a validated semiquantitative nine-item dietary questionnaire;
      patients were divided into low, intermediate, and high adherence. Insulin
      resistance was defined by the 75th percentile of homeostasis model of insulin
      resistance (HOMA-IR; >=3.8). RESULTS: The mean age was 56.2+/-12.4 years and
      38.2% were women. Liver steatosis was present in 82.7%, and its prevalence
      decreased from low to high adherence group (96.5% vs. 71.4%, P<0.001). In a
      multiple logistic regression analysis, hypertriglyceridemia (odds ratio (OR):
      2.913; P=0.002), log (ALT) (OR: 6.186; P<0.001), Med-Diet adherence (intermediate
      vs. low OR: 0.115; P=0.041, high vs. low OR: 0.093; P=0.030), T2DM (OR: 3.940;
      P=0.003), and high waist circumference (OR: 3.012; P<0.001) were associated with
      NAFLD. Among single foods, low meat intake (OR: 0.178; P<0.001) was inversely
      significantly associated with NAFLD. In 334 non-diabetic NAFLD patients, age (OR:
      1.035, P=0.025), high waist circumference (OR: 7.855, P<0.001),
      hypertriglyceridemia (OR: 2.152, P=0.011), and Log (ALT) (OR: 2.549, P=0.002)
      were directly associated with HOMA-IR, whereas Med-Diet score was inversely
      associated (OR: 0.801, P=0.018). CONCLUSIONS: We found an inverse relationship
      between Med-Diet and NAFLD prevalence. Among NAFLD patients, good adherence to
      Med-Diet was associated with lower insulin resistance. Our findings suggest that
      Med-Diet may be a beneficial nutritional approach in NAFLD patients.

PMID- 29063910
TI  - Health status of long-term sick leave and working female teachers in Germany: A
      cross-sectional study.
AB  - OBJECTIVES: Limited research on the health situation of teachers on long-term
      sick leave is available. The aim of this study has been to describe the health
      status of female teachers on long-term sick leave (LSFT) in comparison to working
      female teachers (WFT) and to determine predictors for their state of mental
      health (MH) and cardiovascular fitness (CF). MATERIAL AND METHODS: Twenty-eight
      LSFT and 300 WFT (average age: 53+/-5 years old) participated in a screening
      diagnostic inventory. Mental health, CF, blood pressure (BP), body mass index
      (BMI), body fat mass (BFM), health behavior (smoking, alcohol intake, physical
      activity) and disease burden (DB - number of medical diagnoses) were analyzed for
      the purpose of characterization of the health status. The multiple linear
      regression analysis was performed to identify predictors for the state of MH and
      CF. RESULTS: Adverse values for the MH but also for CF, BFM and the DB (median of
      medical diagnoses: LSFT: 5; WFT: 2) among the LSFT in comparison to the WFT were
      confirmed. Additionally, the part of smokers among LSFT (25%) was higher (WFT:
      8%). In contrast, the WFT (61%) were much more affected by an elevated BP (LSFT:
      26%). Disease burden proved as the strongest predictor for MH of the female
      teachers. Age, BMI and DB proved as predictors for CF. CONCLUSIONS: Health
      related differences between long-term sick leave and working teachers were
      particularized and a link between physical and mental health among teachers was
      quantified. Therefore, health-related concepts for teachers should equally focus
      on physical and psychological aspects. The relevance of regular well-structured
      occupational health check-ups should be brought to the attention of the
      profession to prevent diseases and early retirements. Int J Occup Med Environ
      Health 2018;31(2):227-242.

PMID- 29063907
TI  - Beyond binding: antibody effector functions in infectious diseases.
AB  - Antibodies play an essential role in host defence against pathogens by
      recognizing microorganisms or infected cells. Although preventing pathogen entry
      is one potential mechanism of protection, antibodies can control and eradicate
      infections through a variety of other mechanisms. In addition to binding and
      directly neutralizing pathogens, antibodies drive the clearance of bacteria,
      viruses, fungi and parasites via their interaction with the innate and adaptive
      immune systems, leveraging a remarkable diversity of antimicrobial processes
      locked within our immune system. Specifically, antibodies collaboratively form
      immune complexes that drive sequestration and uptake of pathogens, clear toxins,
      eliminate infected cells, increase antigen presentation and regulate
      inflammation. The diverse effector functions that are deployed by antibodies are
      dynamically regulated via differential modification of the antibody constant
      domain, which provides specific instructions to the immune system. Here, we
      review mechanisms by which antibody effector functions contribute to the balance
      between microbial clearance and pathology and discuss tractable lessons that may
      guide rational vaccine and therapeutic design to target gaps in our infectious
      disease armamentarium.

PMID- 29063913
TI  - [Letter to the Editor (June 27, 2017) concerning the paper "Factors affecting
      exposure level for medical staff during orthopedic procedures under fluoroscopic
      control"].

PMID- 29063911
TI  - [Occupational cancers - Epidemiology and certification].
AB  - The etiology of cancer is multifactorial. Malignant tumors caused by factors
      occurring in the work environment, classified as carcinogenic in humans, can be
      recognized as an occupational disease. Analysis of epidemiological data indicates
      a significant underestimation of occupational cancer, mainly due to long latency
      period of these diseases. This publication provides guidance to certify
      occupational etiology of malignant tumors, based on the reviews of existing
      legislation and medical literature, as well as on the experience of their
      authors. The publication presents the epidemiology of cancers, including
      occupational cancers, risk factors, occupational carcinogens and presents the
      principles of occupational cancer certification. Med Pr 2018;69(1):93-108.

PMID- 29063912
TI  - [Importance of dental care to maintain oral health of children and youth with
      type 1 diabetes].
AB  - BACKGROUND: Dental care for children and youth with type 1 diabetes should rely
      on reliable examination of the oral cavity, early treatment of dental caries and
      maintenance of the treatment results. This can be achieved through regular
      control visits consistent with the standards, and also through following the
      recommendations for prevention of dental caries and periodontal disease. The aim
      of the study was to investigate whether dental care allows to preserve good oral
      health of children and youth with type 1 diabetes. MATERIAL AND METHODS: The
      study included 60 patients with type 1 diabetes, aged 7-17 years, and 30 healthy
      children and youth within the same age range. There were evaluated intensity of
      caries, the effectiveness of conservative treatment, periodontal health and oral
      hygiene. RESULTS: The results of examinations showed significantly lower caries
      prevalence and better periodontal health in the children and youth with type 1
      diabetes. The effectiveness of conservative treatment was significantly higher
      among patients with mixed dentition. There was no significant difference in oral
      hygiene between the compared groups. CONCLUSIONS: Diabetes is a risk factor for
      oral diseases, so children and youth with type 1 diabetes should be provided with
      special preventive care and curative measures. The main goal of the insulin
      dependent diabetes care program is to early classify them to highrisk groups to
      improve general oral health and thus improve the quality of life. Proper dental
      care for children and yuoth with type 1 diabetes is a condition to maintain oral
      health. Med Pr 2018;69(1):37-44.

PMID- 29063914
TI  - A new developing class of gene delivery: messenger RNA-based therapeutics.
AB  - Gene therapy has long been held as having the potential to become a front line
      treatment for various genetic disorders. However, the direct delivery of nucleic
      acids to correct a genetic disorder has numerous limitations owing to the
      inability of naked nucleic acids (DNA and RNA) to traverse the cell membrane.
      Recently, messenger RNA (mRNA) based delivery has become a more attractive
      alternative to DNA due to the relatively easier transfection process, higher
      efficiency and safety profile. As with all gene therapies, the central challenge
      that remains is the efficient delivery of nucleic acids intracellularly. This
      review presents the recent progress in mRNA delivery, focusing on comparing the
      advantages and limitations of non-viral based delivery vectors.

PMID- 29063927
TI  - Dealloying-directed synthesis of efficient mesoporous CoFe-based catalysts
      towards the oxygen evolution reaction and overall water splitting.
AB  - It is a great challenge to design highly active, stable and low-cost catalysts
      for electrochemically splitting water to realize the clean energy generation and
      renewable energy storage. Herein, a facile one-step dealloying strategy was
      proposed to synthesize mesoporous CoFe-based oxides and layered double hydroxides
      (LDHs). Benefitting from the fast mass transfer and more active sites caused by
      the open mesoporous structure, the CoFe-based materials exhibit excellent
      electrocatalytic activities and stability towards the oxygen evolution reaction
      (OER) in an alkaline electrolyte (1 M KOH). The CoFe-LDH catalyst only needs an
      overpotential of 0.286 V to achieve 10 mA cm-2, and a small Tafel slope of 45 mV
      dec-1 for the OER. Moreover, an alkaline electrolyzer was constructed with the
      CoFe-LDH as both the anode and cathode. The electrolyzer delivers a current
      density of 10 mA cm-2 at a voltage of 1.69 V toward overall water splitting in
      the 1 M KOH solution.

PMID- 29063928
TI  - Shell thickness effects on quantum dot brightness and energy transfer.
AB  - Heterostructured core/shell quantum dots (QDs) are prized in biomedical imaging
      and biosensing applications because of their bright, photostable emission and
      effectiveness as Forster resonance energy transfer (FRET) donors. However, as
      nanomaterials chemistry has progressed beyond traditional QDs to incorporate new
      compositions, ultra-thick shells, and alloyed structures, few of these materials
      have had their optical properties systematically characterized for effective
      application. For example, thick-shelled QDs, also known as 'giant' QDs (gQDs) are
      useful in single-particle tracking microscopy because of their reduced blinking,
      but we know only that CdSe/CdS gQDs are qualitatively brighter than thin-shelled
      CdSe/CdS in aqueous media. In this study, we quantify the impact of shell
      thickness on the nanoparticle molar extinction coefficient, quantum yield,
      brightness, and effectiveness as a FRET donor for CdSe/xCdS core/shell and
      CdSe/xCdS/ZnS core/shell/shell QDs, with variable thicknesses of the CdS shell
      (x). Molar extinction coefficients up to three orders of magnitude higher than
      conventional dyes and forty-fold greater than traditional QDs are reported. When
      thick CdS shells are combined with ZnS capping, quantum yields following thiol
      ligand exchange reach nearly 40%-5-10* higher than either the commercially
      available QDs or gQDs without ZnS caps treated the same way. These results
      clearly show that thick CdS shells and ZnS capping shells work in concert to
      provide the brightest possible CdSe-based QDs for bioimaging applications. We
      demonstrate that thicker shelled gQDs are over 50-fold brighter than their thin
      shelled counterparts because of significant increases in their absorption cross
      sections and higher quantum yield in aqueous milieu. Consistent with the point
      dipole approximation commonly used for QD-FRET, these data show that thick shells
      contribute to the donor-acceptor distance, reducing FRET efficiency. Despite the
      reduction in FRET efficiency, even the thickest-shell gQDs exhibited energy
      transfer. Through this systematic study, we elucidate the tradeoffs between
      signal output, which is much higher for the gQDs, and FRET efficiency, which
      decreases with shell thickness. This study serves as a guide to
      nanobiotechnologists striving to use gQDs in imaging and sensing devices.

PMID- 29063930
TI  - Sensitive and specific detection of explosives in solution and vapour by surface
      enhanced Raman spectroscopy on silver nanocubes.
AB  - Surface-enhanced Raman spectroscopy (SERS) has been widely utilised as a
      sensitive analytical technique for the detection of trace levels of organic
      molecules. The detection of organic compounds in the gas phase is particularly
      challenging due to the low concentration of adsorbed molecules on the surface of
      the SERS substrate. This is particularly the case for explosive materials, which
      typically have very low vapour pressures, limiting the use of SERS for their
      identification. In this work, silver nanocubes (AgNCs) were developed as a highly
      sensitive SERS substrate with very low limit-of-detection (LOD) for explosive
      materials down to the femtomolar (10-15 M) range. Unlike typical gold-based
      nanostructures, the AgNCs were found suitable for the detection of both aromatic
      and aliphatic explosives, enabling detection with high specificity at low
      concentration. SERS studies were first carried out using a model analyte,
      Rhodamine-6G (Rh-6G), as a probe molecule. The SERS enhancement factor was
      estimated as 8.71 * 1010 in this case. Further studies involved femtomolar
      concentrations of 2,4-dinitrotoluene (DNT) and nanomolar concentrations of 1,3,5
      trinitroperhydro-1,3,5-triazine (RDX), as well as vapour phase detection of DNT.

PMID- 29063933
TI  - Signal self-enhancement by coordinated assembly of gold nanoparticles enables
      accurate one-step-immunoassays.
AB  - Current immunoassays are in general performed through time-consuming multi-step
      procedures that depend on the use of premade signal-producing reporters and often
      cause assay inaccuracy. Here we report an advanced immunoassay technology that
      resolves the delayed, complex, and inaccurate assay problems of conventional
      immunoassays. We have developed an accurate, rapid, simple, and label-free one
      step-immunoassay based on the self-enhancement of sensitive immunoassay signals
      in an assay solution. The nano-scale protein particles (hepatitis B virus capsid
      and human ferritin heavy chain particles) were genetically engineered to present
      many well-oriented antibody (or antigen) probes and multi-copies of poly
      histidine peptides on their surface, resulting in the construction of 3
      dimensional (3D) bioprobes that chemisorb gold ions via coordination bonding and
      sensitively detect both antigen and antibody analytes. Systematic numerical and
      experimental analyses show that the signal self-enhancement happens through two
      coupled reactions under reducing conditions: (1) 3D bioprobe-based sensitive
      immuno-detection of analytes and (2) coordinated assembly of free and chemisorbed
      gold nanoparticles around the 3D bioprobe-analyte-associated complexes, which is
      followed by the quick generation of apparent optical signals. This advanced one
      step-immunoassay was successfully applied to diagnostic assays requiring high
      accuracy and/or speed, i.e. diagnosis of acute myocardial infarction and
      hepatitis C through detecting a cardiac protein (troponin I) and anti-hepatitis C
      virus antibodies in patient sera, indicating that it is applicable to the
      accurate and rapid detection of both antigen and antibody markers of a wide range
      of diseases.

PMID- 29063940
TI  - On the nanosecond proton dynamics in phosphoric acid-benzimidazole and phosphoric
      acid-water mixtures.
AB  - The unique proton conduction mechanism of phosphoric acid is important for the
      functions of complex phosphate containing biological and technological systems
      (e.g. phospholipid membranes and polybenzimidazole phosphoric acid membranes for
      high-temperature PEM fuel cells). In neat phosphoric acid structural proton
      diffusion, i.e. proton hopping between phosphoric acid molecules, is superimposed
      onto hydrodynamic diffusion of the molecules in the viscous liquid. In this study
      we separate the two dynamic contributions on the nanosecond timescale for the
      model systems phosphoric acid-water and phosphoric acid-benzimidazole. We
      demonstrate that 1H NMR dipolar relaxation measurements are controlled by
      hydrodynamic diffusion for the investigated conditions, while 17O NMR quadrupolar
      relaxation measurements reflect local proton displacement as part of structural
      diffusion. Quasielastic neutron scattering (QENS) applying high resolution
      backscattering spectroscopy (nBSS) confirms structural proton diffusion
      measurements using PFG-NMR in phosphoric acid-benzimidazole mixtures at different
      concentrations. With increasing benzimidazole content proton diffusion
      coefficients on the nanosecond scale decrease, thus following the trend of
      reduced hydrogen bond network frustration. The momentum transfer (Q) dependence
      of the width of the QENS spectra indicates the jump diffusion mechanism and can
      be scaled to a master plot both for different temperatures and different
      benzimidazole contents. This indicates a fundamentally unchanged structural
      proton diffusion process, however, with a lower probability of occurrence for
      successful intermolecular proton transfer with increasing benzimidazole content.
      Results of this work enable a better separation of different diffusion processes
      on short timescales also in more complex phosphoric acid containing systems.

PMID- 29063941
TI  - Experimental and theoretical study of the collisional quenching of S(1D) by Ar.
AB  - We present an experimental and theoretical investigation of the deactivation rate
      of S(1D) atoms by collisions with argon. Kinetic measurements were performed at
      temperatures from 5.8 K to 298 K in cold uniform supersonic flows using a CRESU
      (Cinetique de Reaction en Ecoulement Supersonique Uniforme or Reaction Kinetics
      in a Uniform Supersonic Flow) apparatus. In order to simulate them, ab initio
      electronic structure calculations using internally contracted MRCI methodology
      were performed to describe the interaction. Starting from them, close-coupling
      calculations were carried out to determine collisional quenching probabilities
      for the transition S(1D) -> S(3P) in the energy range 1-3000 K (1 K ~ 0.7 cm-1),
      sufficient to calculate thermal rate coefficients up to 300 K. Stuckelberg-like
      oscillations in the quenching probabilities as a function of the energy are found
      and interpreted using a semiclassical model. Differences between the temperature
      dependence of the experimental and theoretical rate coefficients are detected at
      low temperatures. They are discussed in the light of a study of the high
      sensitivity of the theoretical results to the potential curves, due to the
      interference mechanisms which underlie the process.

PMID- 29063942
TI  - Pure zero-dimensional Cs4PbBr6 single crystal rhombohedral microdisks with high
      luminescence and stability.
AB  - Zero-dimensional (0D) perovskite Cs4PbBr6 has been speculated to be an efficient
      solid-state emitter, exhibiting strong luminescense on achieving quantum
      confinement. Although several groups have reported strong green luminescence from
      Cs4PbBr6 powders and nanocrystals, doubts that the origin of luminescence comes
      from Cs4PbBr6 itself or CsPbBr3 impurities have been a point of controversy in
      recent investigations. Herein, we developed a facile one-step solution self
      assembly method to synthesize pure zero-dimensional rhombohedral Cs4PbBr6 micro
      disks (MDs) with a high PLQY of 52% +/- 5% and photoluminescence full-width at
      half maximum (FWHM) of 16.8 nm. The obtained rhombohedral MDs were high quality
      single-crystalline as demonstrated by XRD and SAED patterns. We demonstrated that
      Cs4PbBr6 MDs and CsPbBr3 MDs were phase-separated from each other and the strong
      green emission comes from Cs4PbBr6. Power and temperature dependence spectra
      evidenced that the observed strong green luminescence of pure Cs4PbBr6 MDs
      originated from direct exciton recombination in the isolated octahedra with a
      large binding energy of 303.9 meV. Significantly, isolated PbBr64- octahedra
      separated by a Cs+ ion insert in the crystal lattice is beneficial to maintaining
      the structural stability, depicting superior thermal and anion exchange
      stability. Our study provides an efficient approach to obtain high quality single
      crystalline Cs4PbBr6 MDs with highly efficient luminescence and stability for
      further optoelectronic applications.

PMID- 29063943
TI  - Real-space imaging of translational and rotational dynamics of hard spheres from
      the fluid to the crystal.
AB  - Using real-space imaging of single particles, we investigate the interplay
      between translational and rotational motion of tracer particles in suspensions of
      colloidal particles over a wide range of volume fractions from dilute fluid to
      densely packed crystal. To this end, we introduce a new type of spherical
      colloidal tracer particles containing two differently labelled fluorescent cores.
      The tracer particles can be combined with host particles enclosing a single
      fluorescent core and chemical and physical properties identical to the tracers.
      This leads to a system of spherical colloidal particles, in which spatio-temporal
      trajectories of rotation and translation of individual particles can be recorded
      simultaneously with full 360 degrees  resolution of rotational dynamics. Our
      analysis shows that translation and rotation of colloidal particles are
      uncorrelated and decoupled for all volume fractions irrespective of the phase of
      the particle system.

PMID- 29063945
TI  - A screening tool for the risk of disability retirement due to musculoskeletal
      disorders.
AB  - Objective This study aimed to develop and validate a risk screening tool using a
      points system to assess the risk of future disability retirement due to
      musculoskeletal disorders (MSD). Methods The development population, the Health
      2000 Survey, consisted of a nationally representative sample of Finnish employees
      aged 30-60 years (N=3676) and the validation population, the Helsinki Health
      Study, consisted of employees of the City of Helsinki aged 40-60 years (N=6391).
      Both surveys were linked to data on disability retirement awards due to MSD from
      national register for an 11-year follow-up. Results The discriminative ability of
      the model with seven predictors was good (Gonen and Heller's K concordance
      statistic=0.821). We gave points to seven predictors: sex-dependent age, level of
      education, pain limiting daily activities, multisite musculoskeletal pain,
      history of arthritis, and surgery for a spinal disorder or carpal tunnel
      syndrome. A score of 3 or higher out of 7 (top 30% of the index) had good
      sensitivity (83%) and specificity (70%). Individuals at the top 30% of the risk
      index were at 29 [95% confidence interval (CI) 15-55) times higher risk of
      disability retirement due to MSD than those at the bottom 40%. Conclusion This
      easy-to-use screening tool based on self-reported risk factor profiles can help
      identify individuals at high risk for disability retirement due to MSD.

PMID- 29063946
TI  - The Effect of Nitric Oxide Pollution on Oxidative Stress in Pregnant Women Living
      in Durban, South Africa.
AB  - The purpose of the study was to evaluate the effect nitric oxide (NO x )
      pollution had on maternal serum 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG)
      levels and neonatal outcomes in pregnant women living in Durban, South Africa
      (SA). Women, in their third trimester with singleton pregnancies, were recruited
      from the heavily industrialised south (n = 225) and less industrialised north (n
      = 152). Biomarker levels of serum 8-OHdG concentrations were analysed, and the
      women were genotyped for glutathione-S-transferases pi 1 (GSTP1) and glutathione
      S-transferases mu 1 (GSTM1) polymorphisms. The level of NO x pollution in the two
      regions was determined by using land use regression modelling. The serum 8-OHdG
      was shown to correlate significantly with NO x levels; this relationship was
      strengthened in the south (p < 0.05). This relationship was still observed after
      adjusting for maternal characteristics. GSTP1 was significantly associated with
      the south region, where the variant (AG+GG) genotype was associated with
      increased 8-OHdG levels as a result of NO x exposure (p < 0.05). GSTM1 null
      genotype was associated with a positive correlation between NO x and 8-OHdG
      levels (p < 0.05). NO x levels were found marginally to reduce gestational age (p
      < 0.05) with mothers carrying male neonates. Variant GSTP1 and living in the
      north were factors that contributed to gestational age reduction (p < 0.05). Our
      study demonstrated that NO x exposure resulted in increased 8-OHdG levels in
      pregnant women living in Durban, SA, which led to gestational age reduction. The
      GSTP1 variant increased susceptibility of individuals to harmful effects of NO x
      .

PMID- 29063947
TI  - Retinoic acid regulates endometriotic stromal cell growth through upregulation of
      Beclin1.
AB  - PURPOSE: To elucidate the role of retinoic acid (RA) in autophagy-mediated
      endometriosis. METHODS: The mRNA and protein expressions of autophagy markers
      were examined in Ishikawa cells and endometriotic stromal cells (ESCs) after RA
      treatment. Beclin1 expression was specifically analyzed in clinical samples of
      endometriosis. The effect of Beclin1 knockdown on ESC growth was assessed, and
      the effect of autophagy inhibition on the sensitivity of endometriotic cells to
      RA was analyzed. RESULTS: RA treatment enhanced the autophagy in ESCs, and
      Beclin1 expression showed a negative correlation with the clinical stage of
      endometriosis. Beclin1 knockdown enhanced ESC growth, whereas RA treatment
      reversed this effect. Furthermore, inhibition of autophagy by chloroquine (CQ)
      and Beclin1 knockdown did not show any positive effect on the sensitivity of
      endometriotic cells to RA. CONCLUSIONS: RA treatment induces autophagy and
      Beclin1 may play an important role in endometriosis progression.

PMID- 29063948
TI  - Uncommon mutation types of epidermal growth factor receptor and response to EGFR
      tyrosine kinase inhibitors in Chinese non-small cell lung cancer patients.
AB  - PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is
      the standard therapy for advanced lung adenocarcinomas with common EGFR
      mutations. However, the efficacy of EGFR-TKIs in patients with uncommon EGFR
      mutations (other than exon 19 deletions or exon 21 L858R mutation) remains
      undetermined. METHODS: Seven hundred and fifty-five non-small cell lung cancer
      (NSCLC) patients with EGFR mutation analyses for TKI therapy were identified
      between October 2010 and December 2015 in East of China. And 66 patients bearing
      uncommon EGFR mutations were included to collect data from TKI response and
      prognosis. We categorised EGFR uncommon mutations as: sensitizing rare mutations
      (group 1: G719X, L861Q, S768I); Ex20 ins (group 2), or complex mutations (G719X +
      L861Q, G719X + S768I, 19 del + T790M, 19 del + L858R, L858R + S768I, and L858R +
      T790M; group 3). RESULTS: Of 66 patients given EGFR-TKI treatment, rare sensitive
      mutations, Ex20 ins, and complex mutations were identified in 37 (56.1%), 9
      (13.6%), and 20 (33.3%) cases, respectively. TKI efficacy in patients harboring
      uncommon EGFR mutations exhibited a tumor response rate of 28.8% and a median
      progression-free survival (PFS) of 4.8 months. Additionally, patients with
      complex EGFR mutations had significantly longer PFS when compared with the
      remaining sensitizing rare mutations or Ex20 ins cases (8.6 vs. 4.1 vs. 3.1
      months; p = 0.041). Importantly, complex EGFR mutations were independent
      predictors of increased overall survival (Hazard Ratios = 0.31; 95% confidence
      intervals: 0.11-0.90; p = 0.031). Among them, patients harboring Del-19 combined
      with L858R mutations showed a tendency to have higher response rate (RR) and
      improved PFS than those with other complex mutation patterns (RR: 66.7 vs. 14.3%,
      p = 0.021; PFS: 10.1 vs. 8.6 months, p = 0.232). CONCLUSIONS: Personalized
      treatment should be evolving in different types of uncommon EGFR mutations.
      Clinical benefit from EGFR-TKIs was higher in NSCLC patients with complex EGFR
      mutations than those with other uncommon EGFR mutation types.

PMID- 29063950
TI  - [Report of the chairman of the Working Group for Head and Neck Pathology of the
      German Society for Pathology : Annual activities 2016/2017].

PMID- 29063949
TI  - Bovine colostrum supplementation does not affect plasma I-FABP concentrations
      following exercise in a hot and humid environment.
AB  - PURPOSE: To quantify the impact of a 14-day bovine colostrum (BC) supplementation
      on intestinal cell damage following exercise in a hot and humid environment.
      METHODS: Ten male participants (20 +/- 2 years, VO2max 55.80 +/- 3.79 mL kg-1 min
      1, 11.81 +/- 2.71% body fat) ran for 46 +/- 7.75 min at 95% of ventiliatory
      threshold in 40  degrees C and 50% RH following a 14-day double-blinded
      supplementation with either BC or placebo (Plac). Core temperature, skin
      temperature, heart rate, and rating of perceived exertion were recorded every 5
      min during exercise. Blood was taken pre, post, 1 h, and 4 h post exercise.
      Intestinal cell damage was assessed via intestinal fatty acid binding protein (I
      FABP). RESULTS: I-FABP concentrations were similar between conditions at all time
      points [pre 989.39 +/- 490.88 pg ml-1 (BC) 851.35 +/- 450.71 pg ml-1 (Plac) post
      1505.10 +/- 788.63 pg ml-1 (BC) 1267.12 +/- 521.51 pg ml-1 (Plac) 1-h, 1087.77 +/
      397.06 pg ml-1 (BC) 997.25 +/- 524.74 pg ml-1 (Plac) 4-h, 511.35 +/- 243.10 pg
      ml-1 (BC) 501.46 +/- 222.54 pg ml-1 (Plac)]. I-FABP was elevated pre to post
      exercise for both BC (162 +/- 50%) and Plac (162 +/- 56%) (p < 0.05). BC had no
      effect on mean body temperature [beginning 36.11 +/- 0.30  degrees C, ending:
      39.52 +/- 0.28  degrees C (BC); beginning:35.96 +/- 0.43  degrees C, ending:39.42
      +/- 0.38  degrees C (Plac)]. CONCLUSIONS: While BC supplementation may protect
      against enterocyte damage during exercise in thermonuetral environments, our data
      suggest that BC supplementation may not be an effective technique for preventing
      enterocyte damage during exercise when core temperature exceeds 39  degrees C.

PMID- 29063951
TI  - [Biliary tract cancers : Molecular characterization and identification of novel
      prognostic markers].
AB  - BACKGROUND: Bile duct cancers (BTCs) are highly aggressive tumors with a dismal
      prognosis and an increasing incidence. BTC is a tumorbiologically and clinically
      heterogeneous tumor group and can be subdivided according to anatomical aspects
      into intrahepatic cholangiocarcinomas (iCCA), extrahepatic cholangiocarcinomas
      (eCCA) and gallbladder carcinomas (GBC). NEW THERAPY OPTIONS: Chronic
      inflammatory processes of the biliary system seem to play a role in the
      development of these tumors. Insights into molecular cholangiocarcinogenesis
      could make an important contribution to novel and more precise classification
      attempts and to the development of new, targeted therapies for BTC. EPIGENETIC
      AND GENETIC ALTERATIONS IN CHOLANGIOCARCINOMAS: The first description of genome
      wide DNA methylation patterns in CCA showed drastic global methylation
      differences between CCA and corresponding non-neoplastic tissue (matched-pair
      analyses). Moreover, significant methylation differences between the CCA subtypes
      (eCCA and iCCA) could be found. Using immunohistochemistry and Sanger sequencing,
      it was shown that the actual BRAF V600E mutation rate seems to be significantly
      lower (1.3%) than previously described in the literature. IMMUNEPHENOTYPING IN
      BILIARY TRACT CANCERS: A comprehensive, subtype-specific characterization of
      tumor-infiltrating immune cells as well as an expression analysis of Major
      Histocompatibility Complex I was performed in a large and well-characterized BTC
      cohort. For further studies on the efficacy of immunomodulatory therapy
      approaches for BTC, the presented results provide a solid basis.

PMID- 29063954
TI  - A gastroenterologist's perspective on the role of barium esophagography in
      gastroesophageal reflux disease.
AB  - Although endoscopy is a sophisticated technique for evaluating patients with
      gastroesophageal reflux disease (GERD), the single diagnostic test that enables
      the most comprehensive assessment for GERD is a well-performed video esophagram.
      Not only does the barium study permit assessment of morphologic abnormalities in
      the pharynx and esophagus, but also oropharyngeal swallowing function, esophageal
      motility, and gastroesophageal reflux. These factors are especially important for
      detection of anatomic findings such as strictures and hernias, for assessment of
      esophageal motility before and after fundoplication, and for excluding conditions
      that mimic GERD. Thus, esophagography and esophagoscopy are complementary
      procedures that provide a more comprehensive and therapeutically actionable plan
      for patients with GERD than either diagnostic test alone.

PMID- 29063953
TI  - Magnetic Resonance Myocardial Perfusion Imaging: Safety and Indications in
      Pediatrics and Young Adults.
AB  - The purpose of this study was to assess the safety and indications for cardiac
      magnetic resonance (CMR) with myocardial perfusion imaging (MPI) in a cohort of
      children and young adults. A retrospective review of 178 children and young
      adults who underwent CMR with MPI was performed. Studies were categorized based
      on study protocols as MPI with resting perfusion only, adenosine stress MPI,
      exercise-induced stress MPI, and MPI for cardiac mass diagnosis. Relevant
      clinical history, exam indications, and adverse reactions following gadolinium
      based contrast agent and adenosine administration were recorded. Studies were
      reviewed for the presence of myocardial perfusion defects, wall motion
      abnormalities, and delayed myocardial enhancement. The most common indications
      from MPI were congenital heart disease (CHD), Kawasaki disease, anomalous
      coronary artery, or myocardial mass characterization. Of these, 51% were
      protocoled with adenosine stress, 23% without stress, 6% with exercise stress,
      and 20% for cardiac mass evaluation. Excluding patients for myocardial mass
      evaluation, MPI defects were present in 16% (14 with adenosine stress, 1 with
      exercise stress, 8 on resting studies only). For cardiac mass evaluation, a mass
      was confirmed in 58%. No adverse reactions occurred with intravenous
      administration of a gadolinium-based contrast agent. Three self-limited adverse
      reactions, 2 patients with chest pain, and 1 patient with bradycardia, occurred
      following adenosine administration. MPI is a safe modality for the evaluation of
      pediatric and young adults with minimal adverse events. The most common
      indications for MPI were for the evaluation of CHD, Kawasaki disease, anomalous
      coronary artery, or myocardial mass characterization.

PMID- 29063956
TI  - Jean Cruveilhier and his contributions to understanding childhood hydrocephalus,
      Chiari II malformation, and spina bifida.

PMID- 29063955
TI  - Novel agent-based salvage autologous stem cell transplantation for relapsed
      multiple myeloma.
AB  - High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is
      a standard frontline therapy for multiple myeloma (MM). Therapeutic options for
      patients with relapsed MM after ASCT include novel agents in different combos,
      salvage ASCT (sASCT), and allogeneic transplant, with no unique standard of care.
      We retrospectively analyzed 66 MM patients who relapsed after up-front single or
      double ASCT(s) and received novel agent-based sASCT at five Italian centers.
      Median event-free survival from up-front ASCT(s) to first relapse (EFS1) was 44
      months. Seventy-three percent of patients received sASCT at first disease
      progression. Re-induction regimens were bortezomib based in 87% of patients.
      Response to re-induction therapy included complete response (CR) 18%, >= very
      good partial response (VGPR) 48%, and overall response rate (ORR) 83%. Response
      to sASCT included CR 44%, >= VGPR 77%, and ORR 94%. With a median follow-up of 24
      months after sASCT, 39 patients experienced disease progression. Median EFS from
      sASCT (EFS2) was 17 months. Median overall survival from ASCT (OS1) and sASCT
      (OS2) was 166 and 43 months, respectively. EFS2 and OS2 were significantly
      shorter in patients with EFS1 <= 24 months, in patients who did not receive sASCT
      at first disease progression and in patients with extramedullary disease (EMD).
      In multivariate analysis, EFS1 <= 24 months was associated with shorter EFS2 and
      OS2, EMD was associated with shorter EFS2, and < CR after sASCT was associated
      with shorter OS2. Novel agent-based sASCT is a safe and effective procedure for
      relapsed MM.

PMID- 29063957
TI  - Significance of H3K27M mutation with specific histomorphological features and
      associated molecular alterations in pediatric high-grade glial tumors.
AB  - PURPOSE: Pediatric high-grade gliomas (pHGGs) constitute almost 15% of all
      childhood brain tumors. Recurrent mutations such as H3K27M mutation in H3F3A and
      HIST1H3B genes encoding histone H3 and its variants were identified in
      approximately 30% of pediatric glioblastomas. This study aimed to ascertain the
      morphological and molecular characteristics of pHGGs with H3K27M mutation.
      METHODS: In total, 61 cases of pHGGs (anaplastic astrocytoma, 12; glioblastomas,
      49) from four university hospitals were studied. The histomorphological features
      were examined and immunohistochemistry was performed to evaluate the mutation
      status of H3K27M, ATRX, IDH1, BRAF V600E, and p53 genes. RESULTS: The study
      comprised 25 females and 36 males (age range, 1-18 years) with a clinical follow
      up of up to 108 months. From the total, 31 patients were positive for H3K27M
      mutation located in the midline, mostly in the pons and thalamus. H3K27M mutation
      was commonly associated with ATRX loss (32.3%) and p53 (74.2%) immunoreactivity
      with a co-expression rate of 25.8%. While IDH1 mutation was not detected in pHGGs
      with H3K27M mutation, BRAFV600E mutation was rarely observed. Among the various
      histomorphological features, increased number of mitosis, increased Ki-67
      proliferation index, and palisading and geographical necrosis along with small
      cell patterns were significantly associated with the H3K27M wild-type tumors.
      Focal infarct-like necrosis and pilomyxoid morphology was significantly
      associated with these tumors. CONCLUSION: H3K27M mutation occurs exclusively in
      pHGGs arising from the midline and presents with varied histomorphological
      features ranging from low-grade pilomyxoid astrocytoma to highly pleomorphic
      glioblastoma along with ATRX loss and p53 mutations.

PMID- 29063958
TI  - Identification and characterization of a novel chemically induced allele at the
      planar cell polarity gene Vangl2.
AB  - Planar cell polarity (PCP) signaling controls a number of morphogenetic processes
      including convergent extension during gastrulation and neural tube formation.
      Defects in this pathway cause neural tube defects (NTD), the most common
      malformations of the central nervous system. The Looptail (Lp) mutant mouse was
      the first mammalian mutant implicating a PCP gene (Vangl2) in the pathogenesis of
      NTD. We report on a novel chemically induced mutant allele at Vangl2 called Curly
      Bob that causes a missense mutation p.Ile268Asn (I268N) in the Vangl2 protein.
      This mutant segregates in a semi-dominant fashion with heterozygote mice
      displaying a looped tail appearance, bobbing head, and a circling behavior.
      Homozygote mutant embryos suffer from a severe form of NTD called
      craniorachischisis, severe PCP defects in the inner hair cells of the cochlea and
      posterior cristae, and display a distinct defect in retinal axon guidance. This
      mutant genetically interacts with the Lp allele (Vangl2 S464N ) in neural tube
      development and inner ear hair cell polarity. The Vangl2I268N protein variant is
      expressed at very low levels in affected neural and retinal tissues of mutant
      homozygote embryos. Biochemical studies show that Vangl2I268N exhibits impaired
      targeting to the plasma membrane and accumulates in the endoplasmic reticulum.
      The Vangl2I268N variant no longer physically interacts with its PCP partner DVL3
      and has a reduced protein half-life. This mutant provides an important model for
      dissecting the role of Vangl2 in the development of the neural tube,
      establishment of polarity of sensory cells of the auditory and vestibular
      systems, and retinal axon guidance.

PMID- 29063960
TI  - Neurodevelopmental outcome in survivors of hypoxic ischemic encephalopathy
      without cerebral palsy.
AB  - : To access outcome following hypoxic ischemic encephalopathy (HIE), survivors
      without cerebral palsy were invited for formal developmental assessment. Children
      aged >= 42 months were assessed using the NEPSY-2, Movement Assessment Battery
      for Children 2 (Movement ABC-2), Behavior Rating Inventory of Executive Function,
      and the Child Behavior Checklist. Children aged < 42 months were assessed using
      the Bayley Scales of Infant and Toddler Development, Third Edition (BSITD-3). One
      hundred forty-six children attended for assessments [Grade 1 (112), Grade 2 (33),
      and Grade 3 (1)]. BSITD-3 did not identify significant rates of impairment on
      cognitive, motor, or language subtests. A significant proportion of children
      scored < 3rd percentile on the adaptive behavior scale. In older age groups,
      difficulties were seen in 16/24 NEPSY-2 subtests and on timed assessments using
      Movement ABC-2. Difficulties arose especially in the "control" aspects of
      cognition and behavior. Behavioral difficulties were common with internalizing
      problems predominating. There was a graded effect with grade 2 cases differing
      significantly from grade 1 cases. CONCLUSION: Following HIE, children may
      experience attention, memory, and behavior difficulties which are not always
      evident at a young age. The adaptive behavior questionnaire may be a useful tool
      to select children requiring developmental surveillance beyond 2 years of age.
      What is known: * Diversity of outcome across grades of HIE is reported and few
      studies have looked at the milder consequences of HIE at school age. What is new:
      * Following HIE children may experience attention, memory, and behavior
      difficulties which are not always evident at a young age. * The adaptive behavior
      questionnaire may be a useful tool to select children requiring developmental
      surveillance beyond 2 years of age.

PMID- 29063959
TI  - Update on investigations pertaining to the pathogenesis of biliary atresia.
AB  - Biliary atresia is a devastating biliary disease of neonates that results in
      liver transplantation for the vast majority. The etiology of biliary atresia is
      unknown and is likely multifactorial, with components of genetic predisposition,
      environmental trigger and autoimmunity contributing to disease pathogenesis. This
      review highlights recent work related to investigations of disease pathogenesis
      in biliary atresia.

PMID- 29063961
TI  - Genome-wide identification and expression analysis of the B-box gene family in
      the Apple (Malus domestica Borkh.) genome.
AB  - The B-box proteins (BBXs) are a family of zinc finger proteins containing one/two
      B-box domain(s). Compared with intensive studies of animal BBXs, investigations
      of the plant BBX family are limited, though some specific plant BBXs have been
      demonstrated to act as transcription factors in the regulation of flowering and
      photomorphogenesis. In this study, using a global search of the apple (Malus
      domestica Borkh.) genome, a total of 64 members of BBX (MdBBX) were identified.
      All the MdBBXs were divided into five groups based on the phylogenetic
      relationship, numbers of B-boxes contained and whether there was with an
      additional CCT domain. According to the characteristics of organ-specific
      expression, MdBBXs were divided into three groups based on the microarray
      information. An analysis of cis-acting elements showed that elements related to
      the stress response were prevalent in the promoter sequences of most MdBBXs.
      Twelve MdBBX members from different groups were randomly selected and exposed to
      abiotic stresses. Their expressions were up-regulated to some extent in the roots
      and leaves. Six among 12 MdBBXs were sensitive to osmotic pressure, salt, cold
      stress and exogenous abscisic acid treatment, with their expressions enhanced
      more than 20-fold. Our results suggested that MdBBXs may take part in response to
      abiotic stress.

PMID- 29063963
TI  - Does Oxidative Stress Play a Role in Altered Characteristics of Diabetic Bone? A
      Systematic Review.
AB  - Diabetes mellitus (DM) has been associated with increased bone fracture rates,
      impaired bone regeneration, delayed bone healing, and depressed osteogenesis.
      However, the plausible pathogenic mechanisms remain incompletely understood. The
      aim of the present systematic review was to investigate whether oxidative stress
      (OS) plays a role in altered characteristics of diabetic bone under in vivo
      conditions. An electronic search of the MEDLINE (via PubMed) and Embase databases
      was performed. In vivo animal studies involving DM and providing information
      regarding assessment of OS markers combined with analyses of bone
      histology/histomorphometry parameters were selected. A descriptive analysis of
      selected articles was performed. Ten studies were included in the present review.
      Both bone formation and bone resorption parameters were significantly decreased
      in the diabetic groups of animals compared to the healthy groups. This finding
      was consistent regardless of different animal/bone models employed or different
      evaluation periods. A statistically significant increase in systemic and/or local
      OS status was also emphasised in the diabetic groups in comparison to the healthy
      ones. Markers of OS were associated with histological and/or histomorphometric
      parameters, including decreased trabecular bone and osteoid volumes, suppressed
      bone formation, defective bone mineralisation, and reduced osteoclastic activity,
      in diabetic animals. Additionally, insulin and antioxidative treatment proved to
      be efficient in reversing the deleterious effects of high glucose and associated
      OS. The present findings support the hypotheses that OS in the diabetic condition
      contributes at least partially to defective bone features, and that antioxidative
      supplementation can be a valuable adjunctive strategy in treating diabetic bone
      disease, accelerating bone healing, and improving osteointegration.

PMID- 29063962
TI  - Association of PGC-1alpha gene with type 2 diabetes in three unrelated endogamous
      groups of North-West India (Punjab): a case-control and meta-analysis study.
AB  - PGC-1alpha (Peroxisome proliferator-activated receptor gamma, coactivator 1
      alpha) plays a key role in glucose homeostasis inside liver and muscle. The
      impact of six polymorphisms of PGC-1alpha with Type 2 Diabetes (T2D)
      susceptibility was evaluated on 1125 samples comprising of 554 T2D cases and 571
      controls among three endogamous groups (Bania, Brahmin and Jat Sikh) of North
      West India (Punjab). Single-locus analysis showed a significant differential
      pattern of genetic association of PGC-1alpha among studied groups emphasizing the
      role of ethnicity towards disease susceptibility. Haplotypes G-A-G-G-C-C in Bania
      group; G-G-G-G-C-A in Brahmin; G-A-A-G-T-C, G-G-G-G-T-C in Jat Sikh groups
      conferred ~ two to fivefold increased T2D risk. Intriguingly, the haplotype
      combination G-A-G-G-C-C provided T2D risk in Banias whereas it played a
      protective role in Brahmins reflecting the role of ethnic heterogeneity. In the
      secondary structure prediction of mRNA, slight free energy change along with
      structural changes was observed between the wild and variant allele of rs3736265,
      rs8192678 and rs2970847 loci. Meta-analyses conducted on rs8192678 and rs2970847
      variants illustrated the overall effect of minor alleles providing a higher risk
      for the T2D development. Divergence in genetic variants and haplotype
      combinations associated with T2D risk among studied groups is inferred from the
      present dataset, which strongly highlights the combinatorial effect of diverse
      ethnic background of the population under study with genetics towards
      susceptibility to complex diseases like T2D.

PMID- 29063965
TI  - Prognostic and influencing factors of tinnitus in chronic otitis media after
      tympanoplasty.
AB  - The purpose of this study is to investigate what characteristics of tinnitus in
      patients with chronic otitis media was reduced after tympanoplasty and to assess
      the relationship between post-operative tinnitus reduction and pre-operative
      tinnitus tone, tinnitus duration, post-operative hearing recovery, and
      tympanogram. Medical records were prospective between March 2013 and May 2016.
      Audiologic evaluation by pure tone audiometry and acoustic impedance and tinnitus
      assessment using scores on the Tinnitus Handicap Inventory (THI) was conducted
      preoperatively and 6 months post-operatively. The data were analyzed using the
      Wilcoxon test, Student's and paired t test, and ANOVA. The pre-operative
      incidence of tinnitus in patients with COM was 47%. There was a very significant
      difference between pre-operative and post-operative mean THI scores (p < 0.05).
      Tinnitus was reduced or alleviated in 83% of tinnitus patients. Pre-operative low
      tone tinnitus was significantly reduced 6 months after surgery. After surgery,
      air-conducted hearing improvement at 250, 500, and 1000 Hz in the tinnitus
      significant recovery group was greater than the tinnitus non-significant recovery
      group (p < 0.05). Tinnitus reduction in tympanogram A was significantly greater
      than in tympanograms B or C (p < 0.05). There was no statistically significant
      correlation between tinnitus duration and tinnitus reduction (p > 0.05). There
      was no significant effect of presence cholesteatoma and dry period on the gain
      THI (p > 0.05). The types of tympanoplasty had no effect on tinnitus improvement
      (p > 0.05). No patients experienced new tinnitus after surgery. Following
      tympanoplasty, most patients experienced a reduction in tinnitus. Pre-operative
      low-tone tinnitus is easier to reduce after tympanoplasty. Post-operative normal
      tympanogram and improved low-frequency AC hearing were important to tinnitus
      reduction.

PMID- 29063966
TI  - The Draft Genome Sequence of Clostridium beijerinckii NJP7, a Unique Bacterium
      Capable of Producing Isopropanol-Butanol from Hemicellulose Through Consolidated
      Bioprocessing.
AB  - A wild type solventogenic Clostridium beijerinckii NJP7 capable of converting
      polysaccharides, such as hemicellulose, into butanol and isopropanol via a unique
      acetone-isopropanol-butanol (AIB) pathway was isolated and characterized. This
      represents the first wild type isopropanol-butanol generating bacterium which
      could achieve butanol production directly from lignocellulose through
      consolidated bioprocessing (CBP). Strain NJP7 was isolated from decomposite soil
      from Laoshan Nature Park, China, and its genome shows 98.6% identical to 89.5% of
      the Clostridium diolis submitted genome sequence. The assembled draft genome
      contains 5.76 Mb and 5101 predicted encoding proteins with a GC content of
      29.73%. Among these annotated proteins, hemicellulase and the secondary alcohol
      dehydrogenase play key roles in achievement of AIB production from hemicellulose
      through CBP.

PMID- 29063964
TI  - Phytocannabinoids modulate emotional memory processing through interactions with
      the ventral hippocampus and mesolimbic dopamine system: implications for
      neuropsychiatric pathology.
AB  - Growing clinical and preclinical evidence suggests a potential role for the
      phytocannabinoid cannabidiol (CBD) as a pharmacotherapy for various
      neuropsychiatric disorders. In contrast, delta-9-tetrahydrocannabinol (THC), the
      primary psychoactive component in cannabis, is associated with acute and
      neurodevelopmental propsychotic side effects through its interaction with central
      cannabinoid type 1 receptors (CB1Rs). CB1R stimulation in the ventral hippocampus
      (VHipp) potentiates affective memory formation through inputs to the mesolimbic
      dopamine (DA) system, thereby altering emotional salience attribution. These
      changes in DA activity and salience attribution, evoked by dysfunctional VHipp
      regulatory actions and THC exposure, could predispose susceptible individuals to
      psychotic symptoms. Although THC can accelerate the onset of schizophrenia, CBD
      displays antipsychotic properties, can prevent the acquisition of emotionally
      irrelevant memories, and reverses amphetamine-induced neuronal sensitization
      through selective phosphorylation of the mechanistic target of rapamycin (mTOR)
      molecular signaling pathway. This review summarizes clinical and preclinical
      evidence demonstrating that distinct phytocannabinoids act within the VHipp and
      associated corticolimbic structures to modulate emotional memory processing
      through changes in mesolimbic DA activity states, salience attribution, and
      signal transduction pathways associated with schizophrenia-related pathology.

PMID- 29063967
TI  - Sequence Analysis of Changes in Microbial Composition in Different Milk Products
      During Fermentation and Storage.
AB  - The objective of this study was to analyze the changes in the microbiota of milk
      products during fermentation and storage. Two kinds of Yoghurt, one Kefir, and
      one Acidophilus milk were observed during the fermentation process and storage
      using 16S rDNA amplicon sequencing. Cow's, goat's, raw and pasteurized milk were
      also examined. The most represented organisms in all manufactured products were
      shown to be those of the phylum Firmicutes. In some products, Proteobacteria,
      Bacteroidetes and Actinobacteria were also present in high amounts.

PMID- 29063968
TI  - Draft Genome Sequence of Cyclohexylamine-Degrading Strain Acinetobacter sp. YT-02
      Isolated.
AB  - Acinetobacter sp. YT-02, a Gram-negative bacterium isolated from the activated
      sludge from a sodium N-cyclohexylsulfamate production plant, has the ability to
      degrade cyclohexylamine. It was classified as a member of Acinetobacter sp., a
      Gram-negative bacterium, sharing a 16S rRNA gene sequence identity of 99% with
      Acinetobacter guangdongensis strain 1NM-4. It could degrade 10 mmol/L
      cyclohexylamine within 22 h. Based on the identified metabolite, the metabolic
      pathway of cyclohexylamine could be postulated as it was degraded via
      cyclohexanone. Draft genome sequence of this strain (2,993, 647 bp of chromosome
      length) is presented here. We further identified the genes encoding the enzymes
      involved in cyclohexylamine oxidation to cyclohexanone and the subsequent
      downstream metabolic pathway of cyclohexanone oxidation. Strain YT-02 has the
      potentiality to be applied in the treatment of the pollutant cyclohexylamine, and
      it could also be treated as a research material to study the degradation
      mechanism of cyclohexylamine.

PMID- 29063969
TI  - Neisseria flavescens: A Urease-Expressing Potential Pathogen Isolated from
      Gastritis Patients.
AB  - Parasitic pathogens, such as H. pylori (Helicobacter pylori), are considered as
      primary elements for causing stomach infection and leading to chronic gastritis
      or ulcers. Here, an unreported urease- and oxidase-producing Neisseria flavescens
      like bacteria was isolated from the gastroscopic biopsies of 14C-UBT-positive
      gastritis patients. The isolate expressed the activity of urease, which is a
      pathogenic factor and considered as a reliable marker for diagnosis of H. pylori
      infection. However, the isolate didn't express the key functional genes of H.
      pylori including vacA and hpaA, and also the morphological feature of isolate was
      significantly different with H. pylori. Eventually, the 16S rDNA of isolate was
      sequenced and its sequence shared about 99.8% similarity with the N. flavescens
      standard strains, but about 20.8% similarity with the H. pylori. Further study of
      antibiotics-resistance revealed the N. flavescens isolate is high resistant to
      metronidazole, but highly sensitive to ampicillin sodium. To summarize, a urease
      expressing N. flavescens strain was isolated and identified from Chinese
      gastritis patients; the encouraging results provides an important reference for
      the further study of its pathogenicity and the reasonable diagnosis and use of
      antibiotics clinically.

PMID- 29063970
TI  - Borosilicate Glass Fiber-Optic Biosensor for the Detection of Escherichia coli.
AB  - Polyclonal antibodies against Escherichia coli and fluorescent, secondary,
      antibodies were immobilized on borosilicate glass fibers pre-treated with 3
      glycidyloxypropyl trimethoxysilane (GPS). Light with an average wavelength of 627
      nm, emitted by a diode placed at one end of the glass fiber, was detected by an
      ultrasensitive photodiode with peak sensitivity at 640 nm. Changes in
      fluorescence, caused by binding of E. coli to the antibodies, changed the net
      refractive index of the glass fiber and thus the internal reflection of light.
      These evanescent changes in photon energy were recorded by an ultrasensitive
      photodiode. Signals were amplified and changes in voltage recorded with a digital
      multimeter. A linear increase in voltage readings was recorded over 2 h when 3.0
      * 107 CFU/ml and 2.77 * 109 CFU/ml E. coli were adhered to the antibodies.
      Voltage readings were recorded with E. coli cell numbers from 2 * 103 CFU/ml to 2
      * 106 CFU/ml, but readings remained unchanged for 2 h, indicating that the limit
      of detection is 3.0 * 107 CFU/ml. This simple technology may be used to develop a
      low-cost, portable, fiber-optic biosensor to detect E. coli in infections and may
      have applications in the medical field. Research is in progress to optimize the
      sensitivity of the fiber-optic biosensor and determine its specificity.

PMID- 29063971
TI  - Novel Microbial Sources of Tropane Alkaloids: First Report of Production by
      Endophytic Fungi Isolated from Datura metel L.
AB  - Eighteen endophytic fungi were isolated from various tissues of Datura metel and
      genes encoding for putrescine N-methyltransferase (PMT), tropinone reductase 1
      (TR1) and hyoscyamine 6beta-hydroxylase (H6H) were used as molecular markers for
      PCR-based screening approach for tropane alkaloids (TAs) producing endophytic
      fungi. These fungi were identified taxonomically by sequence analysis of the
      internal transcribed spacer region (ITS1-5.8S-ITS2) and also based on
      morphological characteristics of the fungal spore as Colletotrichum boninense,
      Phomopsis sp., Fusarium solani, Colletotrichum incarnatum, Colletotrichum
      siamense and Colletotrichum gloeosporioides. The production of TAs hyoscyamine
      and scopolamine by the fungi has been ascertained using chromatography and
      spectroscopy methods by comparison with the standards. Among the fungi, the
      highest yields of hyoscyamine (3.9 mg/L) and scopolamine (4.1 mg/L) were found in
      C. incarnatum culture. This is the first report of endophytic fungi possess the
      PMT, TR1 and H6H genes and produces TAs. These endophytic fungi have significant
      potential to be applied in fermentation technology to meet the demands for TAs
      economically.

PMID- 29063973
TI  - Improving Regional Stroke Systems of Care.
AB  - PURPOSE OF REVIEW: Acute ischemic stroke (AIS) care is rapidly evolving. This
      review discusses current diagnostic, therapeutic, and process models that can
      expedite stroke treatment to achieve best outcomes. RECENT FINDINGS: Use of stent
      retrievers after selection via advanced imaging is safe and effective, and is an
      important option for AIS patients with large vessel occlusion (LVO). Significant
      time delays occur before and during patient transfers, and upon comprehensive
      stroke center (CSC) arrival, and have deleterious effects on functional outcome.
      Removing obstacles, enhancing inter-facility communication, and creating acute
      stroke management processes and protocols are paramount strategies to enhance
      network efficiency. Inter-departmental CSC collaboration can significantly reduce
      door-to-treatment times. Streamlined stroke systems of care may result in higher
      treatment rates and better functional outcomes for AIS patients, simultaneously
      conserving healthcare dollars. Stroke systems of care should be structured
      regionally to minimize time to treatment. A proactive approach must be employed;
      a management plan incorporating stroke team prenotification and parallel
      processes between departments can save valuable time, maximize brain salvage, and
      reduce disability from stroke.

PMID- 29063974
TI  - Is Mini-Gastric Bypass a Rational Approach for Type-2 Diabetes?
AB  - PURPOSE OF REVIEW: Morbid obesity and type-2 diabetes mellitus (T2DM) are both
      major public health problems. Bariatric surgery is a proven and effective
      treatment for these conditions; laparoscopic Roux-en-Y gastric bypass (RYGB) is
      currently the gold-standard treatment. One-anastomosis gastric bypass (OAGB) is
      described as a simpler, safer, and non-inferior alternative to RYGB to treat
      morbid obesity. Concerning T2DM, experts of the OAGB procedure report promising
      metabolic results with good long-term remission of T2DM; however, heterogeneity
      within the literature prompted us to analyze this issue. RECENT FINDINGS: OAGB
      has gained popularity given its safety and long-term efficacy. Concerning the
      effect of OAGB for the treatment of T2DM, most reports involve non-controlled
      single-arm studies with heterogeneous methodologies and a few randomized
      controlled trials. However, this available literature supports the efficacy of
      OAGB for remission of T2DM in obese and non-obese patients. Two years after OAGB,
      the T2DM remission and improvement rate increased from 67 to 100%. The results
      were improved and stable in the long term. The 5-year T2DM remission rate
      increased from 82 to 84.4%. OAGB is non-inferior compared with RYGB and even
      superior to other accepted bariatric procedures, such as sleeve gastrectomy and
      adjustable gastric banding. OAGB is an efficient, safe, simple, and reversible
      procedure to treat T2DM. The literature reveals interesting results for T2DM
      remission in non-obese patients. High-level comparative studies are required to
      support these data.

PMID- 29063975
TI  - Reliability of the Parabola Approximation Method in Heart Rate Variability
      Analysis Using Low-Sampling-Rate Photoplethysmography.
AB  - Photoplethysmographic signals are useful for heart rate variability analysis in
      practical ambulatory applications. While reducing the sampling rate of signals is
      an important consideration for modern wearable devices that enable 24/7
      continuous monitoring, there have not been many studies that have investigated
      how to compensate the low timing resolution of low-sampling-rate signals for
      accurate heart rate variability analysis. In this study, we utilized the parabola
      approximation method and measured it against the conventional cubic spline
      interpolation method for the time, frequency, and nonlinear domain variables of
      heart rate variability. For each parameter, the intra-class correlation, standard
      error of measurement, Bland-Altman 95% limits of agreement and root mean squared
      relative error were presented. Also, elapsed time taken to compute each
      interpolation algorithm was investigated. The results indicated that parabola
      approximation is a simple, fast, and accurate algorithm-based method for
      compensating the low timing resolution of pulse beat intervals. In addition, the
      method showed comparable performance with the conventional cubic spline
      interpolation method. Even though the absolute value of the heart rate
      variability variables calculated using a signal sampled at 20 Hz were not exactly
      matched with those calculated using a reference signal sampled at 250 Hz, the
      parabola approximation method remains a good interpolation method for assessing
      trends in HRV measurements for low-power wearable applications.

PMID- 29063976
TI  - RELA fusion-positive anaplastic ependymoma: molecular characterization and
      advanced MR imaging.

PMID- 29063977
TI  - Highly-expressed polyamine oxidases catalyze polyamine back conversion in
      Brachypodium distachyon.
AB  - To understand the polyamine (PA) catabolic pathways in Brachypodium distachyon,
      we focused on the flavin-containing polyamine oxidase enzymes (PAO), and
      characterized them at the molecular and biochemical levels. Five PAO isoforms
      were identified from database searches, and we named them BdPAO1 to BdPAO5. By
      gene expression analysis using above-ground tissues such as leaf, stem and
      inflorescence, it was revealed that BdPAO2 is the most abundant PAO gene in
      normal growth conditions, followed by BdPAO3 and BdPAO4. BdPAO1 and BdPAO5 were
      expressed at very low levels. All Arabidopsis thaliana and rice orthologs
      belonging to the same clade as BdPAO2, BdPAO3 and BdPAO4 have conserved
      peroxisome-targeting signal sequences at their C-termini. Amino acid sequences of
      BdPAO2 and BdPAO4 also showed such a sequence, but BdPAO3 did not. We selected
      the gene with the highest expression level (BdPAO2) and the peroxisome-targeting
      signal lacking PAO (BdPAO3) for biochemical analysis of substrate specificity and
      catabolic pathways. BdPAO2 catalyzed conversion of spermine (Spm) or
      thermospermine to spermidine (Spd), and Spd to putrescine, but its most-favored
      substrate was Spd. In contrast, BdPAO3 favored Spm as substrate and catalyzed
      conversion of tetraamines to Spd. These results indicated that the major PAOs in
      B. distachyon have back-conversion activity.

PMID- 29063978
TI  - Mst1 regulates colorectal cancer stress response via inhibiting Bnip3-related
      mitophagy by activation of JNK/p53 pathway.
AB  - The Hippo-Mst1 pathway is associated with tumor development and progression.
      However, little evidence is available for its role in colorectal cancer (CRC)
      stress response via mitochondrial homeostasis. In this study, we conducted gain
      of function assay about Mst1 in CRC via adenovirus transfection. Then, cellular
      viability and apoptosis were measured via MTT, TUNEL assay, and typan blue
      staining. Mitochondrial function was detected via JC1 staining, mPTP opening
      assay, and immunofluorescence of cyt-c. Mitophagy was observed via western blots
      and immunofluorescence. Cell migration and proliferation were evaluated via
      Transwell and BrdU assay. Western blots were used to analyze the signaling
      pathways with JNK inhibitors or p53 siRNA. We found that Mst1 was down-regulated
      in CRC. Overexpression of Mst1 induced CRC apoptosis and impaired cell
      proliferation and migration. Functional studies have illustrated that recovery of
      Mst1 could activate JNK pathway which upregulated the p53 expression. The latter
      repressed Bnip3 transcription and activity, leading to the mitophagy arrest. The
      defective mitophagy impaired mitochondrial homeostasis, evoked cellular oxidative
      stress, and initiated the mitochondrial apoptosis. Meanwhile, bad-structured
      mitophagy also hindered the cancer proliferation via CyclinD/E. Moreover, Mst1
      suppressed mitophagy was associated with CRC migration inhibition via regulation
      of CXCR4/7 expression. Collectively, our data described the comprehensive role of
      Mst1 in colorectal cancer stress response involving apoptosis, mobilization, and
      growth via handling mitophagy by JNK/p53/Bnip3 pathways.

PMID- 29063979
TI  - Transanal total mesorectal excision with triangle rules: a road map to prevent
      injuries.

PMID- 29063980
TI  - Bilateral acute angle closure glaucoma and myopic shift by topiramate-induced
      ciliochoroidal effusion: case report and literature review.
AB  - PURPOSE: To report two cases of ciliochoroidal effusion after the usage of
      topiramate. CASES: Two middle-aged women experienced sudden onset of acute
      glaucoma and acquired myopia after taking topiramate. Ultrasound biomicroscopy
      demonstrated bilateral ciliochoroidal effusion and angle closure. The A-scan
      ultrasonography revealed shallow anterior chamber and thick lens. After the
      treatment and drug withdrawal, intraocular pressure, refractive status and angle
      anatomy returned to normal and there was resolution of ciliochoroidal effusion.
      During the clinical course, the anterior chamber depth (ACD) increased from 2.02
      to 3.30 mm (1.28 mm of changes) OD and from 1.94 to 3.36 mm (1.42 mm of changes)
      OS. The lens thickness (LT) became thinner from 4.53 to 4.31 mm (0.22 mm of
      changes) OD and from 4.59 to 4.30 mm (0.29 mm of changes) OS in the first case.
      In the second case, the ACD increased from 2.33 to 3.07 mm (0.74 mm of changes)
      OD and from 2.30 to 3.05 mm (0.75 mm of changes) OS. The LT became thinner from
      4.42 to 4.27 mm (0.15 mm of changes) OD and from 4.38 to 4.26 mm (0.12 mm of
      changes) OS. The forward displacement of the lens-iris diaphragm contributed more
      to the shallowness of the anterior chamber than the thickening of the lens itself
      (only accounting for 20%). CONCLUSION: Topiramate-induced bilateral acute angle
      closure glaucoma and myopic shift was due to ciliochoroidal effusion which
      resulted in thicker lens and shallow anterior chamber. The later was mainly due
      to anterior displacement of the lens-iris diaphragm.

PMID- 29063981
TI  - The effect of genetic variants on the relationship between statins and breast
      cancer in postmenopausal women in the Women's Health Initiative observational
      study.
AB  - PURPOSE: Statins have been postulated to have chemopreventive activity against
      breast cancer. We evaluated whether germline genetic polymorphisms modified the
      relationship between statins and breast cancer risk using data from the Women's
      Health Initiative. We evaluated these interactions using both candidate gene and
      agnostic genome-wide approaches. METHODS: To identify candidate gene-statin
      interactions, we tested interactions between 22 SNPS in nine candidate genes
      implicated in the effect of statins on lipid metabolism in 1687 cases and 1687
      controls. We then evaluated statin use interaction with the remaining 30,380 SNPs
      available in this sample from the CGEMS GWAS study. RESULTS: After adjusting for
      multiple comparisons, no SNP interactions with statin usage and risk of breast
      cancer were statistically significant in either the candidate genes or genome
      wide approaches. CONCLUSIONS: We found no evidence of SNP interactions with
      statin usage for breast cancer risk in a population of 3374 individuals. These
      results suggest that genome-wide common genetic variants do not moderate the
      association between statin usage and breast cancer in the population of women in
      the Women's Health Initiative.

PMID- 29063983
TI  - Retrospective analysis of first-line treatment for follicular lymphoma based on
      outcomes and medical economics.
AB  - BACKGROUND: Follicular lymphoma (FL) is the most common type of non-Hodgkin
      lymphoma (NHL), with indolent progression. Several treatment options are
      selected, based not only on disease status, quality of life (QOL), and age of
      patient, but also on recent increasing medical costs. We retrospectively analysed
      the first-line treatment of FL with regard to treatment outcomes and medical
      economics, and discuss the appropriate strategies for FL. METHODS: Data on a
      total of 69 newly-diagnosed patients with FL was retrospectively collected from
      2001 to 2015. RESULTS: The median age of the patients was 60 years and the median
      follow-up was 58 months. A total of 25 cases with FL were treated with R
      monotherapy, and 28 cases were treated with R-CHOP as first-line treatment. The
      factors affecting the decision of physicians to use R or R-CHOP treatment were
      serum level of lactate dehydrogenase (LDH) and disease stage. The first-line
      treatment-associated survival did not show any statistical differences between R
      and R-CHOP. The average hospitalization and average of all medical costs during
      the first-line treatment were 4.1 days (R) versus 55.7 days (R-CHOP), and JPY
      1,707,693 (USD 15,324) (R) versus JPY 2,136,117 (USD 19,170) (R-CHOP),
      respectively. CONCLUSION: R monotherapy for patients whose diseases show low
      tumor burden and who are not candidates for local treatment has benefits as a
      first-line treatment compared to R-CHOP, based on the patients' QOL and medical
      economics.

PMID- 29063986
TI  - The gesture 'Touch': Does meaning-making develop in chimpanzees' use of a very
      flexible gesture?
AB  - In this bottom-up study of gesture, we focused on the details of a single
      gesture, Touch. We compared characteristics of use by three young chimpanzees
      with those of 11 adults, their interactive partners, housed in a semi-natural
      social group at the Kyoto University Primate Research Institute (KUPRI) in Japan.
      Five hundred eighty-one observations of the gesture Touch were collected across a
      four-year time span. This single gesture had 36 different forms, was directed to
      70 different target locations on the body of social partners, and occurred in 26
      different contexts. Significant differences were found between infant and adult
      initiators in the form, target locations, and contexts of the gesture Touch.
      There was a wide diversity in form-location patterns within each context, and
      there were no form-location patterns specific to particular contexts. Thus, we
      demonstrate that this gesture exhibits flexibility in form and flexibility in
      use. The results from this study illustrate the importance of contextualized
      meaning in understanding flexibility in the gesture use of great apes.

PMID- 29063984
TI  - Esophageal squamous cell neoplasia is an independent negative prognostic factor
      for head and neck cancer patients.
AB  - BACKGROUND: Patients with head and neck cancer (HNC) have a high incidence of
      esophageal squamous cell neoplasms (ESCN). ESCN also has a negative impact on the
      survival of HNC patients. However, recent endoscopic advances enable the early
      detection of ESCN, and novel treatments may lead to improving survival rates for
      HNC patients with ESCN. METHODS: HNC patients who underwent magnifying
      esophagogastroduodenoscopy (EGDS) from 2005 to 2012 were included in this study
      (n = 226). We analyzed the prevalence and prognostic value of ESCN in HNC
      patients and the difference in overall survival between HNC patients with and
      without ESCN. RESULTS: Thirty-four patients (15%) developed an ESCN during their
      clinical course. Of the 34 patients, 10 patients underwent endoscopic resection
      for ESCN and 10 patients underwent simultaneous chemoradiation therapy for HNC
      and ESCN. The 3-year survival rates in HNC patients with and without ESCN were
      53% and 70%, respectively. Multivariate analysis identified the advanced clinical
      stage of the HNC [hazard ratio (HR) = 2.15; 95% confidence interval (CI) = 1.18
      3.93; p = 0.012] and the presence of ESCN (HR = 1.73; 95% CI = 1.00-2.97; p =
      0.049) as significant and independent determinants of overall survival.
      CONCLUSIONS: Our study suggests that although the survival of HNC patients with
      ESCN may be improved by routine EGDS during tumor surveys and by advances in
      endoscopy, the presence of ESCN still remains an independent negative prognostic
      factor for HNC patients.

PMID- 29063982
TI  - Role of Beta-adrenergic Receptors and Sirtuin Signaling in the Heart During
      Aging, Heart Failure, and Adaptation to Stress.
AB  - In the heart, catecholamine effects occur by activation of beta-adrenergic
      receptors (beta-ARs), mainly the beta 1 (beta1-AR) and beta 2 (beta2-AR)
      subtypes, both of which couple to the Gs protein that activates the adenylyl
      cyclase signaling pathway. The beta2-ARs can also couple to the Gi protein that
      counterbalances the effect of the Gs protein on cyclic adenosine monophosphate
      production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling
      pathway. In several cardiovascular disorders, including heart failure, as well as
      in aging and in animal models of environmental stress, a reduction in the
      beta1/beta2-AR ratio and activation of the beta2-AR-Gi-PI3K-Akt signaling pathway
      have been observed. Recent studies have shown that sirtuins modulate certain
      organic processes, including the cellular stress response, through activation of
      the PI3K-Akt signaling pathway and of downstream molecules such as p53, Akt, HIF1
      alpha, and nuclear factor-kappa B. In the heart, SIRT1, SIRT3, and beta2-ARs are
      crucial to the regulation of the cardiomyocyte energy metabolism, oxidative
      stress, reactive oxygen species production, and autophagy. SIRT1 and the beta2-AR
      Gi complex also control signaling pathways of cell survival and death. Here, we
      review the role played by beta2-ARs and sirtuins during aging, heart failure, and
      adaptation to stress, focusing on the putative interplay between the two. That
      relationship, if proven, merits further investigation in the context of cardiac
      function and dysfunction.

PMID- 29063987
TI  - A decision support model to predict the presence of an acute infiltrate on chest
      radiograph.
AB  - A chest infiltrate is needed to make a diagnosis of community-acquired pneumonia,
      but chest X-rays might be time consuming, entail radiation exposure, and demand
      resources that are not always available. We sought to derive a model to predict
      whether a patient will have an infiltrate on chest X-ray (CXR). This prospective
      observational study included patients visiting the Emergency Department of
      Beilinson Hospital in the years 2003-2004 (derivation cohort) and 2010-2011
      (validation cohort), who had undergone a CXR, and were suspected of having a
      respiratory infection. We excluded all patients with possible healthcare
      associated infections. A logistic regression model was derived and applied to the
      validation cohort. A total of 1,555 patients met inclusion criteria: 993 in the
      derivation cohort and 562 in the validation cohort with 287 (29%) and 226 (40%)
      having an infiltrate, respectively. The derivation model area-under-the curve
      (AUC) was 0.79 (95% CI 0.76-0.82). We categorized the patients into three groups
      presence or absence of infiltrate, or undetermined. In the validation cohort, 70
      (12%) patients were classified as 'no infiltrate'; 3 (4%) of them had an
      infiltrate, 367 (65%) were classified as 'infiltrate'; 190 (52%) of them had an
      infiltrate on CXR, and 125 (46%) were classified as 'undetermined'; 33 (26%) of
      them with an infiltrate on CXR. Using this prediction model for the evaluation of
      patients with suspected respiratory infection in an ED setting may help avoid
      over 10% of CXRs.

PMID- 29063988
TI  - Correction to: Biochars mitigate greenhouse gas emissions and bioaccumulation of
      potentially toxic elements and arsenic speciation in Phaseolus vulgaris L.
AB  - The original version of this article unfortunately contained a mistake. One
      affiliation and one author were missing. The corrected affiliations and authors
      are given here.

PMID- 29063989
TI  - Viscous dissipation and dynamics of defects in an active nematic interface?.
AB  - We consider active flow and dynamics of topological defects in an active nematic
      interfacial layer confined between immissible viscous fluid layers. The velocity
      of defects is determined by asymptotic matching of solutions in the defect core
      and the far field. Self-propulsion of positive defects along the direction of
      their "comet tails" is identified as the principal deterministic component of
      defect dynamics, while topological and hydrodynamic interactions among mobile
      defects is responsible for quasi-random jitter.

PMID- 29063990
TI  - Identification and biochemical characterization of WbwB, a novel UDP-Gal: Neu5Ac
      R alpha1,4-galactosyltransferase from the intestinal pathogen Escherichia coli
      serotype O104.
AB  - The intestinal pathogen Escherichia coli serotype O104:H4 (ECO104) can cause
      bloody diarrhea and haemolytic uremic syndrome. The ECO104 O antigen has the
      unique repeating unit structure [4Galalpha1-4Neu5,7,9Ac3alpha2-3Galbeta1
      3GalNAcbeta1-], which includes the mammalian sialyl-T antigen as an internal
      structure. Previously, we identified WbwC from ECO104 as the beta3Gal-transferase
      that synthesizes the T antigen, and showed that alpha3-sialyl-transferase WbwA
      transfers sialic acid to the T antigen. Here we identify the wbwB gene product as
      a unique alpha1,4-Gal-transferase WbwB that transfers Gal from UDP-Gal to the
      terminal sialic acid residue of Neu5Acalpha2-3Galbeta1-3GalNAcalpha-diphosphate
      lipid acceptor. NMR analysis of the WbwB enzyme reaction product indicated that
      Galalpha1-4Neu5Acalpha2-3Galbeta1-3GalNAcalpha-diphosphate-lipid was synthesized.
      WbwB from ECO104 has a unique acceptor specificity for terminal sialic acid as
      well as the diphosphate group in the acceptor. The characterization studies
      showed that WbwB does not require divalent metal ion as a cofactor. Mutagenesis
      identified Lys243 within an RKR motif and both Glu315 and Glu323 of the fourth
      EX7E motif as essential for the activity. WbwB is the final glycosyltransferase
      in the biosynthesis pathway of the ECO104 antigen repeating unit. This work
      contributes to knowledge of the biosynthesis of bacterial virulence factors.

PMID- 29063991
TI  - Mitochondrial DNA content is associated with ploidy status, maternal age, and
      oocyte maturation methods in mouse blastocysts.
AB  - PURPOSE: It was reported that mitochondrial DNA (mtDNA) was significantly
      increased in aneuploid human embryos compared to euploid embryos and was also
      associated with maternal age. In this study, we further established the mouse
      model of mtDNA quantitation in reproductive samples based on whole-genome
      amplification (WGA) and next-generation sequencing (NGS). METHODS: WGA followed
      by NGS-based mtDNA quantitation was first performed on 6 single- and 100-cell
      samples from a tumor-derived mouse cell line, which was exposed to ethidium
      bromide to reduce mtDNA content. The relative mtDNA content was normalized to
      nuclear DNA. This method was then applied to mouse reproductive samples,
      including 40 pairs of oocytes and polar bodies from 8 CD-1 female mice of
      advanced reproductive age and 171 blastocysts derived via in vitro maturation
      (IVM) or in vivo maturation (IVO) from young (6-9 weeks) and reproductively aged
      (13.5 months) female CF-1 mice. RESULTS: Exposure to ethidium bromide for 3 and 6
      days decreased mtDNA levels in both the single- and 100-cell samples as expected.
      Results demonstrated that the first polar body contained an average of 0.9% of
      mtDNA relative to oocytes. Compared to the cells in blastocysts, oocytes
      contained about 180 times as much mtDNA per cell. mtDNA levels were compared
      among blastocysts from reproductively young and old female mice that had either
      been produced by IVM or IVO. Cells in blastocysts from younger mice contained
      significantly lower amounts of mtDNA compared to aged mice (P < 0.0001). Cells in
      blastocysts produced via IVO had higher mtDNA content than IVM-derived
      blastocysts (P = 0.0001). Cells in aneuploid blastocysts were found to have
      significantly higher (1.74-fold) levels of mtDNA compared to euploid blastocysts
      (P = 0.0006). CONCLUSION: A reliable method for assessing mtDNA content in mouse
      gametes and embryos was established. Relative mtDNA levels were elevated in
      aneuploid embryos relative to euploid embryos, were higher in blastocysts from
      reproductively old mice relative to young mice, and were lower in embryos derived
      from IVM compared to IVO.

PMID- 29063993
TI  - Thiophene-Based Organic Semiconductors.
AB  - Thiophene-based pi-conjugated organic small molecules and polymers are the
      research subject of significant current interest owing to their potential use as
      organic semiconductors in material chemistry. Despite simple and similar
      molecular structures, the hitherto reported properties of thiophene-based organic
      semiconductors are rather diverse. Design of high performance organic
      semiconducting materials requires a thorough understanding of inter- and intra
      molecular interactions, solid-state packing, and the influence of both factors on
      the charge carrier transport. In this chapter, thiophene-based organic
      semiconductors, which are classified in terms of their chemical structures and
      their structure-property relationships, are addressed for the potential
      applications as organic photovoltaics (OPVs), organic field-effect transistors
      (OFETs) and organic light emitting diodes (OLEDs).

PMID- 29063992
TI  - FDA-approved drugs that are spermatotoxic in animals and the utility of animal
      testing for human risk prediction.
AB  - PURPOSE: This study reviews FDA-approved drugs that negatively impact spermatozoa
      in animals, as well as how these findings reflect on observations in human male
      gametes. METHODS: The FDA drug warning labels included in the DailyMed database
      and the peer-reviewed literature in the PubMed database were searched for
      information to identify single-ingredient, FDA-approved prescription drugs with
      spermatotoxic effects. RESULTS: A total of 235 unique, single-ingredient, FDA
      approved drugs reported to be spermatotoxic in animals were identified in the
      drug labels. Forty-nine of these had documented negative effects on humans in
      either the drug label or literature, while 31 had no effect or a positive impact
      on human sperm. For the other 155 drugs that were spermatotoxic in animals, no
      human data was available. CONCLUSION: The current animal models are not very
      effective for predicting human spermatotoxicity, and there is limited information
      available about the impact of many drugs on human spermatozoa. New approaches
      should be designed that more accurately reflect the findings in men, including
      more studies on human sperm in vitro and studies using other systems (ex vivo
      tissue culture, xenograft models, in silico studies, etc.). In addition, the
      present data is often incomplete or reported in a manner that prevents
      interpretation of their clinical relevance. Changes should be made to the
      requirements for pre-clinical testing, drug surveillance, and the warning labels
      of drugs to ensure that the potential risks to human fertility are clearly
      indicated.

PMID- 29063994
TI  - High Dietary Protein Intake and Protein-Related Acid Load on Bone Health.
AB  - PURPOSE OF REVIEW: Consumption of high-protein diets is increasingly popular due
      to the benefits of protein on preserving lean mass and controlling appetite and
      satiety. The paper is to review recent clinical research assessing dietary
      protein on calcium metabolism and bone health. RECENT FINDINGS: Epidemiological
      studies show that long-term, high-protein intake is positively associated with
      bone mineral density and reduced risk of bone fracture incidence. Short-term
      interventional studies demonstrate that a high-protein diet does not negatively
      affect calcium homeostasis. Existing evidence supports that the negative effects
      of the acid load of protein on urinary calcium excretion are offset by the
      beneficial skeletal effects of high-protein intake. Future research should focus
      on the role and the degree of contribution of other dietary and physiological
      factors, such as intake of fruits and vegetables, in reducing the acid load and
      further enhancing the anabolic effects of protein on the musculoskeletal system.

PMID- 29063996
TI  - Dr. Google and Premature Consent: Patients Who Trust the Internet More Than They
      Trust Their Provider.
AB  - A growing number of patients make up their minds about some medical issue before
      they see their provider, either by googling their symptoms or asking a friend.
      They've made up their minds before coming in, and they resist their provider's
      recommendations even after receiving information and advice from their provider.
      This is a new kind of medical autonomy problem; it differs from cases of standard
      consent, futility, or conscientious refusal. Providers sometimes call this
      problem "Dr. Google." I call it premature consent. Providers may wonder whether
      these patient decisions command the same deference and respect as other patient
      decisions. The answer is "no," for these patients are neither fully competent nor
      properly informed. They typically appear to be competent, but competence includes
      the ability to deliberate, and they are not deliberating well when they make up
      their minds before consulting a qualified provider. They seem informed,
      especially after talking to their provider, but they are misinformed about what
      sources of medical advice to trust. Moreover, being informed requires believing
      the information one has received, and these patients sometimes don't believe the
      information their provider gives them.

PMID- 29063995
TI  - Psychology as a Science of Subject and Comportment, beyond the Mind and Behavior.
AB  - The turn of qualitative inquiry suggests a more open, plural conception of
      psychology than just the science of the mind and behavior as it is most commonly
      defined. Historical, ontological and epistemological binding of this conception
      of psychology to the positivist method of natural science may have exhausted its
      possibilities, and after having contributed to its prestige as a science, has now
      become an obstacle. It is proposed that psychology be reconceived as a science of
      subject and comportment in the framework of a contextual hermeneutic, social,
      human behavioral science. Thus, without rejecting quantitative inquiry,
      psychology recovers territory left aside like introspection and pre-reflective
      self-awareness, and reconnects with traditions marginalized from the main stream.
      From this perspective psychology might also recover its credibility as a human
      science in view of current skepticism.

PMID- 29063997
TI  - Clinical Ethics Consultation After God: Implications for Advocacy and Neutrality.
AB  - In After God: Morality and Bioethics in a Secular Age, H. Tristram Engelhardt,
      Jr. explores the broad implications for moral reasoning once a culture has lost a
      God's-eye perspective. In this paper, I focus on the implications of Engelhardt's
      views for clinical ethics consultation. I begin by examining the question of
      whether clinical ethics consultants (CECs) should advocate a particular viewpoint
      and/or process during consultations or adopt a neutral stance. I then examine the
      implications of Engelhardt's views for this question. Finally, I discuss some of
      Engelhardt's foundational ontological, metaphysical, meta-ethical, and
      epistemological commitments and how these commitments connect to his views on
      clinical ethics consultation.

PMID- 29063999
TI  - Backbone 1H, 13C and 15N resonance assignments of the OB domain of the single
      stranded DNA-binding protein hSSB2 (NABP1/OBFC2A) and chemical shift mapping of
      the DNA-binding interface.
AB  - Single stranded DNA-binding proteins (SSBs) are essential for the maintenance of
      genome integrity and are required in in all known cellular organisms. Over the
      last 10 years, the role of two new human SSBs, hSSB1 (NABP2/OBFC2B) and hSSB2
      (NABP1/OBFC2A), has been described and characterised in various important DNA
      repair processes. Both these proteins are made up of a conserved oligonucleotide
      binding (OB) fold that is responsible for ssDNA recognition as well a unique
      flexible carboxy-terminal extension involved in protein-protein interactions. Due
      to their similar domain organisation, hSSB1 and hSSB2 have been found to display
      some overlapping functions. However, several studies have also revealed cell- and
      tissue-specific roles for these two proteins, most likely due to small but
      significant differences in the protein sequence of the OB domains. While the
      molecular details of ssDNA binding by hSSB1 has been studied extensively,
      comparatively little is known about hSSB2. In this study, we use NMR solution
      state backbone resonance assignments of the OB domain of hSSB2 to map the ssDNA
      interaction interface. Our data reveal that ssDNA binding by hSSB2 is driven by
      four key aromatic residues in analogy to hSSB1, however, some significant
      differences in the chemical shift perturbations are observed, reflecting
      differences in ssDNA recognition. Future studies will aim at determining the
      structural basis of these differences and thus help to gain a more comprehensive
      understanding of the functional divergences that these novel hSSBs display in the
      context of genome maintenance.

PMID- 29063998
TI  - Diabetes Mellitus and the Colon.
AB  - OPINION STATEMENT: Diabetes mellitus (DM) can affect the structure and function
      of the colon promoting commonly encountered lower gastrointestinal symptoms such
      as constipation, diarrhea, abdominal distention, bloating, and abdominal pain.
      Specific colonic disorders for which adults with DM are at greater risk include
      chronic constipation, enteropathic diarrhea, colorectal cancer (CRC),
      inflammatory bowel disease, microscopic colitis, and Clostridium difficile
      colitis. Smooth muscle structure and function, density of the interstitial cells
      of Cajal, and the health and function of the autonomic and enteric nerves of the
      colon are all potential affected by DM. These effects can in turn lead to
      alterations in colon motility, visceral sensation, immune function, endothelial
      function, and the colonic microbiome. The evaluation and treatment for slow
      transit constipation as well as pelvic floor dysfunction should be considered
      when constipation symptoms are refractory to initial treatment measures. DM
      related medications and small bowel conditions such as celiac disease and small
      intestinal bowel overgrowth should be considered and excluded before a diagnosis
      of enteropathic diarrhea is made. Given the higher risk of CRC, adults with DM
      should be appropriately screened and may require a longer bowel preparation to
      ensure an adequate evaluation.

PMID- 29064000
TI  - 1H, 15N, 13C backbone resonance assignment of the C-terminal domain of enzyme I
      from Thermoanaerobacter tengcongensis.
AB  - Phosphoenolpyruvate binding to the C-terminal domain (EIC) of enzyme I of the
      bacterial phosphotransferase system (PTS) initiates a phosphorylation cascade
      that results in sugar translocation across the cell membrane and controls a large
      number of essential pathways in bacterial metabolism. EIC undergoes an expanded
      to compact conformational equilibrium that is regulated by ligand binding and
      determines the phosphorylation state of the overall PTS. Here, we report the
      backbone 1H, 15N and 13C chemical shift assignments of the 70 kDa EIC dimer from
      the thermophilic bacterium Thermoanaerobacter tengcongensis. Assignments were
      obtained at 70  degrees C by heteronuclear multidimensional NMR spectroscopy. In
      total, 90% of all backbone resonances were assigned, with 264 out of a possible
      299 residues assigned in the 1H-15N TROSY spectrum. The secondary structure
      predicted from the assigned backbone resonance using the program TALOS+ is in
      good agreement with the X-ray crystal structure of T. tengcongensis EIC. The
      reported assignments will allow detailed structural and thermodynamic
      investigations on the coupling between ligand binding and conformational dynamics
      in EIC.

PMID- 29064002
TI  - CEA Response and Depth of Response (DpR) to Predict Clinical Outcomes of First
      Line Cetuximab Treatment for Metastatic Colorectal Cancer.
AB  - BACKGROUND: The decrease in carcinoembryonic antigen (CEA) level is faster and
      greater during cetuximab treatment than bevacizumab treatment and correlates with
      prolonged survival in patients with metastatic colorectal cancer (mCRC) who
      receive cetuximab. OBJECTIVE: We investigated if the degree of change in the CEA
      value can serve as a diagnostic tool for predicting survival, as well as tumor
      regression in mCRC patients treated with cetuximab combined regimen as first-line
      treatment. PATIENTS AND METHODS: Associations among the CEA decrease, depth of
      response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC
      from two phase II trials of first-line therapy: the JACCRO CC-05 trial of
      cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was
      performed using Spearman's rank correlation coefficient. A 75% decrease in the
      CEA was used as the cut-off value to define the CEA response and discriminate CEA
      responders on the basis of the results of a previous study. RESULTS: Ninety-two
      patients were eligible for analyses of both CEA and DpR. The median CEA decrease
      was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to
      the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (rs
      = 0.56, P < 0.0001; rs = 0.39, P = 0.0090, respectively); moreover, the CEA
      decrease correlated with PFS (rs = 0.56, P < 0.0001), as well as OS (rs = 0.35, P
      = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months,
      hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS
      (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA
      decrease was statistically significantly associated with the DpR (rs = 0.44, P <
      0.0001). CONCLUSIONS: Our study demonstrates that both DpR and CEA response
      correlate with clinical outcomes of first-line treatment with cetuximab. The CEA
      decrease may serve as a surrogate for DpR in patients who receive first-line
      cetuximab treatment (UMIN000004197, UMIN000007022).

PMID- 29064001
TI  - Comparison of changes in renal function with dosimetric parameters in gastric
      cancer patients treated with adjuvant chemoradiotherapy.
AB  - PURPOSE: Our objective was to analyze kidney damage using glomerular filtration
      rate (GFR) and dynamic renal scintigraphy (DRS) compared with dose volume
      histogram (DVH) parameters in gastric cancer patients. MATERIALS AND METHODS:
      Twenty-two gastric cancer patients treated with postoperative chemoradiotherapy
      were retrospectively evaluated. Student's t test was used to compare pre- and
      posttreatment GFR and creatinine values. The relative contribution of the left
      and right kidney in DRS results was expressed as left-to-right ratio (L/R), and
      the percentage of initial and control participation ratio difference was
      calculated. Spearman's correlation analysis was used to compare the percentage
      difference of L/R ratio with DVH parameters of each kidney. RESULTS: In DRS
      analysis, decrease in left kidney cortical function was observed in one patient.
      V5-V10 of the left and bilateral kidneys were significantly associated with GFR
      decline. None of the DVH parameter was significantly associated with L/R ratio.
      However, the V15 and Dmean of the bilateral kidney were significantly correlated
      with greater decrease in L/R ratio in seven patients whose posttreatment DRS
      period was > 12 months. CONCLUSIONS: Decline in renal function, even with current
      renal constraints, was observed. Minimization of V5, V10, and V15 and mean dose
      (Dmean) to the kidney should be considered.

PMID- 29064003
TI  - Atypical small acinar proliferation at index prostate biopsy: rethinking the re
      biopsy paradigm.
AB  - PURPOSE: Guidelines for atypical small acinar proliferation (ASAP) diagnosed on
      prostate biopsy recommend repeat biopsy within 3-6 months after diagnosis. We
      sought to discern the rate of detecting clinically significant prostate cancer on
      repeat biopsy and predictors associated with progression. MATERIALS AND METHODS:
      We performed a retrospective chart review of patients who underwent prostate
      biopsy at our institution from January 1, 2008, to December 31, 2015. Gleason
      grade group (GGG) system and D'Amico stratification were used to report pathology
      and risk stratification, respectively. Logistic and linear regression analyses
      were performed. RESULTS: A total of 593 patients underwent transrectal ultrasound
      guided prostate biopsy, of which 27 (4.6%) had the diagnosis of ASAP. Of these,
      11 (41%) had a repeat biopsy. Median time from diagnosis to repeat biopsy was 147
      days (IQR 83.5-247.0). Distribution across the GGG system on repeat biopsy was as
      follows: 7 (63.6%) benign, 3 (27.3%) GG1, and 1 (9.1%) GG2. ASAP was not
      associated with subsequent diagnosis of clinically significant prostate cancer
      (OR 0.46, 95% CI 0.064-3.247, P = 0.432). There was no association between ASAP
      and high cancer risk (ASAP: beta = - 0.12; P = 0.204). CONCLUSIONS: Patients
      diagnosed with ASAP managed according to guideline recommendations are more
      likely diagnosed with benign pathology and indolent prostate cancer on repeat
      biopsy. These findings support prior studies suggesting refinement of guidelines
      in regard to the appropriateness and timeliness of repeat biopsy among patients
      diagnosed with ASAP.

PMID- 29064004
TI  - Outpatient Total Joint Arthroplasty.
AB  - PURPOSE OF REVIEW: Outpatient total joint arthroplasty (OTJA) allows for a safe,
      cost effective pathway for appropriately selected patients. With current
      pressures on arthroplasty surgeons and their associated institutions to reduce
      costs per episode of care, it is important to define the steps and challenges
      associated with establishing an outpatient arthroplasty program. RECENT FINDINGS:
      Several studies have outlined techniques of selecting patients suitable for this
      type of postoperative pathway. With emerging concerns about patients who undergo
      outpatient arthroplasty being at increased risk of medical complications, which
      may lessen projected cost savings, it is important to identify value-based
      strategies to optimize patient recovery after OTJA. This article reviews digital
      techniques for patient selection and data collection, operating room efficiency
      systems, and provides a summary of methods to build and maintain value in
      outpatient total joint replacement within the framework of bundled payment
      reimbursement.

PMID- 29064005
TI  - Obstructive sleep apnea patients without hypertension or diabetes and subsequent
      incidence of chronic kidney disease.

PMID- 29064006
TI  - Characterization of Protein Complexes Using Chemical Cross-Linking Coupled
      Electrospray Mass Spectrometry.
AB  - Identification and characterization of large protein complexes is a mainstay of
      biochemical toolboxes. Utilization of cross-linking chemicals can facilitate the
      capture and identification of transient or weak interactions of a transient
      nature (Huang and Kim, PloS One 8:e61430, 2013; Gao et al., J Vis Exp doi:
      10.3791/51387, 2014). Here we describe a detailed methodology for a cell culture
      based proteomic approach. We describe the generation of cells stably expressing
      green fluorescent protein (GFP)-tagged proteins under the tetracycline-inducible
      promoter and subsequent proteomic analysis of GFP-interacting proteins. We
      include a list of proteins that were identified as interactors of GFP.

PMID- 29064007
TI  - Production of steviol from steviol glucosides using beta-glucosidase from a
      commercial pectinase, Sumizyme PX.
AB  - OBJECTIVE: To purify and characterize a specific enzyme from a commercial
      pectinase for the production of steviol from stevioside (Ste) without adding
      organic solvent and to improve steviol production. RESULTS: Commercial Sumizyme
      PX converted Ste to steviol with a yield of 98%. beta-Glucosidase from Sumizyme
      PX (betaglyPX) was purified in three steps with 12.5-fold purification and 51%
      yield. The specific activity of the purified betaglyPX was 141 U/mg. The
      molecular weight of betaglyPX was ~ 116 kDa on SDS-PAGE. Its optimum activity was
      at pH 3.5 and 65  degrees C. It was stable for 12 h up to 55  degrees C and for
      24 h at pH 2-9.5. K m values of betaglyPX for pNPGal, oNPGlc, lactose, and Ste
      were 2.4, 0.7, 18, and 7.8 mM, respectively. The optimum conditions for steviol
      production were 55  degrees C, 900 U/ml, 80 mg Ste/ml, 12 h. CONCLUSION:
      betaglyPX contains great potential for industrial steviol production from Ste.

PMID- 29064008
TI  - Paediatric population neuroimaging and the Generation R Study: the second wave.
AB  - Paediatric population neuroimaging is an emerging field that falls at the
      intersection between developmental neuroscience and epidemiology. A key feature
      of population neuroimaging studies involves large-scale recruitment that is
      representative of the general population. One successful approach for population
      neuroimaging is to embed neuroimaging studies within large epidemiological
      cohorts. The Generation R Study is a large, prospective population-based birth
      cohort in which nearly 10,000 pregnant mothers were recruited between 2002 and
      2006 with repeated measurements in the children and their parents over time.
      Magnetic resonance imaging was included in 2009 with the scanning of 1070 6-to-9
      year-old children. The second neuroimaging wave was initiated in April 2013 with
      a total of 4245 visiting the MRI suite and 4087 9-to-11-year-old children being
      scanned. The sequences included high-resolution structural MRI, 35-direction
      diffusion weighted imaging, and a 6 min and 2 s resting-state functional MRI
      scan. The goal of this paper is to provide an overview of the imaging protocol
      and the overlap between the neuroimaging data and metadata. We conclude by
      providing a brief overview of results from our first wave of neuroimaging, which
      highlights a diverse array of questions that can be addressed by merging the
      fields of developmental neuroscience and epidemiology.

PMID- 29064010
TI  - Toxicity of Copper Oxide (CuO) Nanoparticles on Human Blood Lymphocytes.
AB  - CuO nanoparticles (CuO-NPs) serve several important functions in human life,
      particularly in the fields of medicine, engineering, and technology. These
      nanoparticles have been utilized as catalysts, semiconductors, sensors, gaseous
      and solid ceramic pigments, and magnet rotatable devices. Further use for CuO-NPs
      has been employed in the pharmaceutical industry especially in the production of
      anti-microbial fabric treatments or prevention of infections caused by
      Escherichia coli and methicillin-resistant Staphylococcus aureus. Two key
      potential routes of exposure to CuO-NPs exist through inhalation and skin
      exposure. Toxicity of these nanoparticles has been reported in various studies;
      however, no study as of yet has investigated the complete cellular mechanisms
      involved in CuO-NPs toxicity on human cells. The aim of this study was to
      determine the cytotoxicity of CuO-NPs on human blood lymphocytes. Blood
      lymphocytes were obtained from healthy male subjects through the use of Ficoll
      polysaccharide subsequently by gradient centrifugation. The following parameters
      were assayed in blood lymphocytes after a 6-h incubation with different
      concentrations of CuO-NPs: cell viability, reactive oxygen species (ROS)
      formation, lipid peroxidation, cellular glutathione levels, and mitochondrial and
      lysosomal damage. Our results demonstrate that CuO-NPs, in particular, decreased
      cell viability in a concentration-dependent manner and the IC50 determined was
      382 MUM. CuO-NP cytotoxicity was associated with significant increase at
      intracellular ROS level and loss of mitochondrial membrane potential and
      lysosomal membrane leakiness. Hence, CuO-NPs are shown to effectively induce
      oxidative stress in addition to inflict damage on mitochondria and lysosomes in
      human blood lymphocytes.

PMID- 29064011
TI  - Using the theory of planned behavior framework for designing interventions
      related to organ donation.

PMID- 29064012
TI  - Challenges Faced by US-Trained Gastroenterologists When Pursuing a Medical Career
      Outside of the USA.

PMID- 29064013
TI  - Ocular, Auricular, and Oral Manifestations of Inflammatory Bowel Disease.
AB  - Inflammatory bowel disease (IBD) is primarily a disease of the gastrointestinal
      tract, though it can often affect other organ systems. These extraintestinal
      manifestations occur in a quarter to one-third of patients with Crohn's disease
      and ulcerative colitis. While musculoskeletal and dermatologic manifestations are
      the most common, it is also important to be cognizant of head, eye, ear, nose,
      and throat (HEENT) manifestations and educate IBD patients about them. Here we
      review the ocular manifestations in conjunction with the lesser-known but
      increasingly recognized ENT manifestations. Considering the lack of randomized
      controlled trials in treating HEENT manifestations of IBD, this review is
      primarily based on case reports, case series, and expert opinion with a
      particular focus on the newer literature supporting use of anti-TNF agents.

PMID- 29064014
TI  - A Statistically Significant Association Between Esophageal Granular Cell Tumors
      and Eosinophilic Esophagitis: A 16-year Analysis at Two Large Hospitals of
      167,434 EGDs.
AB  - BACKGROUND: Esophageal granular cell tumor (eGCT) is a rare, usually benign,
      neoplasm of neuroectodermic origin. Eosinophilic esophagitis (EoE) is a
      relatively uncommon, immune-mediated, chronic disease. Both diseases commonly
      present with dysphagia. One case has been reported of simultaneous occurrence of
      both diseases. AIMS: To determine the association between diseases. METHODS: The
      present study was an IRB-approved, retrospective review of
      esophagogastroduodenoscopies (EGDs) with esophageal biopsies from two large
      hospitals, 1999-2014. RESULTS: Among 29,235 EGDs with esophageal biopsies for 16
      years (167,434 total EGDs), 16 patients had pathologically diagnosed eGCT, and
      1225 patients had pathologically diagnosed EoE. Five (31%) of 16 patients with
      eGCT had concomitant EoE (p = 0.001, OR 10.43, 95% ORCI 3.16-32.44, Fisher's
      exact test). Patients with simultaneous eGCT and EoE were young (mean age = 33.6
      +/- 12.9 years). Three were female. Dysphagia was presenting symptom in 4 (80%)
      of patients. Three had asthma. All five patients had > 20 eosinophils/hpf in
      esophageal biopsy specimens. Three patients had endoscopic esophageal
      abnormalities suggesting EoE. Four patients were treated with a PPI (before and
      after diagnosis of EoE), and 2 patients underwent six-food-elimination diet with
      partial symptomatic improvement. The eGCTs averaged 13.4 +/- 4.2 mm in maximal
      diameter and were located in upper-2, middle-2, and lower esophagus-2 (1 patient
      had 2 eGCTs). eGCTs were endoscopically resected-3 patients, and monitored-2
      patients. Surveillance endoscopies revealed no recurrence or growth of eGCTs
      after resection (mean follow-up = 4.6 years). CONCLUSIONS: This novel report of 5
      patients with simultaneous EoE and eGCT adds to one, previously published case
      and suggests these two diseases are associated, and have a common
      pathophysiologic link, despite apparently different pathogenesis. Large,
      prospective, endoscopic and pathologic studies are warranted to further
      investigate this association.

PMID- 29064015
TI  - Isolated Acute Terminal Ileitis Without Preexisting Inflammatory Bowel Disease
      Rarely Progresses to Crohn's Disease.
AB  - BACKGROUND: Isolated acute terminal ileitis without chronic features of
      inflammation poses a diagnostic challenge. Few studies have investigated the
      clinical significance of this entity in patients without history of inflammatory
      bowel disease. AIMS: We sought to elucidate the long-term prognosis of patients
      with isolated acute terminal ileitis, its rate of progression to Crohn's disease,
      and the factors associated with terminal ileitis development to Crohn's disease.
      METHODS: Retrospective review of clinical, endoscopic, and radiographic records
      was performed on 108 patients with histologic evidence of isolated acute terminal
      ileitis on terminal ileal biopsies obtained by diagnostic ileocolonoscopy
      performed between January 1, 2002, and December 31, 2014, at the Mayo Clinic.
      Statistical analysis was performed with Student's t test and Fisher's exact test
      to identify the factors associated with the progression of isolated acute
      terminal ileitis to Crohn's disease. RESULTS: The median follow-up time across
      108 patients was 54.7 months (interquartile range 32.0-89.0 months). Five
      patients (4.6%) developed Crohn's disease after a median of 32.3 months (7.5-43.2
      months). The presence of narrowing/stricturing (p = 0.03) on abdominal cross
      sectional imaging at the time of terminal ileitis diagnosis was correlated with
      eventual Crohn's disease development. No significant correlation was found with
      clinical symptoms, endoscopic features, laboratory testing, NSAID use, smoking
      history, or family history of inflammatory bowel disease. CONCLUSIONS: Isolated
      acute terminal ileitis discovered on diagnostic ileocolonoscopy rarely develops
      to Crohn's disease. Presence of stricturing/narrowing on cross-sectional imaging
      may predict eventual Crohn's disease development.

PMID- 29064016
TI  - Clinical Features and Outcomes of Gastric Ischemia.
AB  - BACKGROUND AND AIMS: Gastric ischemia is a rare condition associated with poor
      prognosis. Our study aim was to highlight the clinical features and outcomes of
      patients with gastric ischemia. METHODS: A retrospective review of patients
      diagnosed with isolated gastric ischemia at our institution from January 1, 2000,
      to May 5, 2016, was performed. Demographic, clinical, endoscopic, radiologic, and
      outcome variables were abstracted for analysis. RESULTS: Seventeen patients (65%
      men) with mean age of 69.3 +/- 11.3 years and body mass index of 28.8 +/- 11.1
      were identified. The etiologies for gastric ischemia included local vascular
      causes (n = 8), systemic hypoperfusion (n = 4), and mechanical obstruction (n =
      5). The most common presenting symptoms were abdominal pain (65%),
      gastrointestinal bleeding (47%), and altered mental status (23%). The typical
      endoscopic appearance was mucosal congestion and erythema with or without
      ulceration. Gastric pneumatosis and portal venous air were more commonly seen on
      CT imaging. Radiologic and/or surgical intervention was needed in 9 patients,
      while the remaining 8 patients were managed conservatively with acid suppression,
      antibiotics, and nasogastric tube decompression. The median duration of hospital
      stay was 15 days (range 1-36 days). There were no cases of rebleeding and the
      mortality rate as a direct result of gastric ischemia was 24% within 6 months of
      diagnosis. CONCLUSION: Although uncommon, gastric ischemia is associated with
      significant mortality. Endoscopy and CT imaging play an important role in its
      diagnosis. The management of gastric ischemia is dictated by its severity and
      associated comorbidities.

PMID- 29064017
TI  - Looking Back at the Past Year of Stem Cell Reviews and Reports.

PMID- 29064019
TI  - Stability of MRI metrics in the advanced research core of the NCAA-DoD concussion
      assessment, research and education (CARE) consortium.
AB  - The NCAA-DoD Concussion Assessment, Research, and Education (CARE) consortium is
      performing a large-scale, comprehensive study of sport related concussions in
      college student-athletes and military service academy cadets. The CARE "Advanced
      Research Core" (ARC), is focused on executing a cutting-edge investigative
      protocol on a subset of the overall CARE athlete population. Here, we present the
      details of the CARE ARC MRI acquisition and processing protocol along with
      preliminary analyzes of within-subject, between-site, and between-subject
      stability across a variety of MRI biomarkers. Two experimental datasets were
      utilized for this analysis. First, two "human phantom" subjects were imaged
      multiple times at each of the four CARE ARC imaging sites, which utilize
      equipment from two imaging vendors. Additionally, a control cohort of healthy
      athletes participating in non-contact sports were enrolled in the study at each
      CARE ARC site and imaged at four time points. Multiple morphological image
      contrasts were acquired in each MRI exam; along with quantitative diffusion,
      functional, perfusion, and relaxometry imaging metrics. As expected, the imaging
      markers were found to have varying levels of stability throughout the brain.
      Importantly, between-subject variance was generally found to be greater than
      within-subject and between-site variance. These results lend support to the
      expectation that cross-site and cross-vendor advanced quantitative MRI metrics
      can be utilized to improve analytic power in assessing sensitive neurological
      variations; such as those effects hypothesized to occur in sports-related
      concussion. This stability analysis provides a crucial foundation for further
      work utilizing this expansive dataset, which will ultimately be freely available
      through the Federal Interagency Traumatic Brain Injury Research Informatics
      System.

PMID- 29064009
TI  - The Rotterdam Study: 2018 update on objectives, design and main results.
AB  - The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city
      of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine,
      hepatic, neurological, ophthalmic, psychiatric, dermatological,
      otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926
      subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016,
      the cohort is being expanded by persons aged 40 years and over. The findings of
      the Rotterdam Study have been presented in over 1500 research articles and
      reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the
      rationale of the study and its design. It also presents a summary of the major
      findings and an update of the objectives and methods.

PMID- 29064020
TI  - Changes in dynamic resting state network connectivity following aphasia therapy.
AB  - Resting state magnetic resonance imaging (rsfMRI) permits observation of
      intrinsic neural networks produced by task-independent correlations in low
      frequency brain activity. Various resting state networks have been described,
      with each thought to reflect common engagement in some shared function. There has
      been limited investigation of the plasticity in these network relationships after
      stroke or induced by therapy. Twelve individuals with language disorders after
      stroke (aphasia) were imaged at multiple time points before (baseline) and after
      an imitation-based aphasia therapy. Language assessment using a narrative
      production task was performed at the same time points. Group independent
      component analysis (ICA) was performed on the rsfMRI data to identify resting
      state networks. A sliding window approach was then applied to assess the dynamic
      nature of the correlations among these networks. Network correlations during each
      30-second window were used to cluster the data into ten states for each window at
      each time point for each subject. Correlation was performed between changes in
      time spent in each state and therapeutic gains on the narrative task. The amount
      of time spent in a single one of the (ten overall) dynamic states was positively
      associated with behavioral improvement on the narrative task at the 6-week post
      therapy maintenance interval, when compared with either baseline or assessment
      immediately following therapy. This particular state was characterized by minimal
      correlation among the task-independent resting state networks. Increased
      functional independence and segregation of resting state networks underlies
      improvement on a narrative production task following imitation-based aphasia
      treatment. This has important clinical implications for the targeting of
      noninvasive brain stimulation in post-stroke remediation.

PMID- 29064018
TI  - Impact of Human Adipose Tissue-Derived Stem Cells on Malignant Melanoma Cells in
      An In Vitro Co-culture Model.
AB  - This study focuses on the interactions of human adipose tissue-derived stem cells
      (ADSCs) and malignant melanoma cells (MMCs) with regard to future cell-based skin
      therapies. The aim was to identify potential oncological risks as ADSCs could
      unintentionally be sited within the proximity of the tumor microenvironment of
      MMCs. An indirect co-culture model was used to analyze interactions between ADSCs
      and four different established melanoma cell lines (G-361, SK-Mel-5, MeWo and
      A2058) as well as two low-passage primary melanoma cell cultures (M1 and M2).
      Doubling time, migration and invasion, angiogenesis, quantitative real-time PCR
      of 229 tumor-associated genes and multiplex protein assays of 20 chemokines and
      growth factors and eight matrix metalloproteinases (MMPs) were evaluated. Co
      culture with ADSCs significantly increased migration capacity of G-361, SK-Mel-5,
      A2058, MeWo and M1 and invasion capacity of G-361, SK-Mel-5 and A2058 melanoma
      cells. Furthermore, conditioned media from all ADSC-MMC-co-cultures induced tube
      formation in an angiogenesis assay in vitro. Gene expression analysis of ADSCs
      and MMCs, especially of low-passage melanoma cell cultures, revealed an increased
      expression of various genes with tumor-promoting activities, such as CXCL12,
      PTGS2, IL-6, and HGF upon ADSC-MMC-co-culture. In this context, a significant
      increase (up to 5,145-fold) in the expression of numerous tumor-associated
      proteins could be observed, e.g. several pro-angiogenic factors, such as VEGF, IL
      8, and CCL2, as well as different matrix metalloproteinases, especially MMP-2. In
      conclusion, the current report clearly demonstrates that a bi-directional
      crosstalk between ADSCs and melanoma cells can enhance different malignant
      properties of melanoma cells in vitro.

PMID- 29064021
TI  - Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia.
AB  - PURPOSE OF REVIEW: Over the past decade, the pathogenic role of mutations in
      isocitrate dehydrogenases (IDH) 1 and 2, affecting approximately 20% of patients
      with AML, has been defined, allowing for the development of specific therapeutic
      strategies for IDH-mutant AML. In this review, the landscape and progress of
      targeted therapeutics aimed at IDH mutations in AML and related myeloid
      malignancies will be described. RECENT FINDINGS: Since 2013, several mutant IDH
      targeted inhibitors have been developed, and nearly a dozen clinical trials have
      opened specifically for IDH-mutant hematologic malignancies. Preliminary results
      for several of these investigations have shown evidence of safety, tolerability,
      and encouraging evidence of efficacy. Targeting IDH mutations in AML is a
      biologically informed and rational strategy to promote clinical responses,
      primarily through differentiation and maturation of the malignant clone. The use
      of IDH targeted therapy is expected to soon become part of a genomically defined
      and individualized AML treatment strategy.

PMID- 29064023
TI  - Diagnostic and Prognostic Utility of Fluorescence In situ Hybridization (FISH)
      Analysis in Acute Myeloid Leukemia.
AB  - PURPOSE OF REVIEW: Acute myeloid leukemia (AML) is a hematologic neoplasia
      consisting of incompletely differentiated hematopoietic cells of the myeloid
      lineage that proliferate in the bone marrow, blood, and/or other tissues.
      Clinical implementation of fluorescence in situ hybridization (FISH) in
      cytogenetic laboratories allows for high-resolution analysis of recurrent
      structural chromosomal rearrangements specific to AML, especially in AML with
      normal karyotypes, which comprises approximately 33-50% of AML-positive
      specimens. Here, we review the use of several FISH probe strategies in the
      diagnosis of AML. We also review the standards and guidelines currently in place
      for use by clinical cytogenetic laboratories in the evaluation of AML. RECENT
      FINDINGS: Updated standards and guidelines from the WHO, ACMG, and NCCN have
      further defined clinically significant, recurring cytogenetic anomalies in AML
      that are detectable by FISH. FISH continues to be a powerful technique in the
      diagnosis of AML, with higher resolution than conventional cytogenetic analysis,
      rapid turnaround time, and a considerable diagnostic and prognostic utility.

PMID- 29064022
TI  - Novel Pathways and Potential Therapeutic Strategies for Blastic Plasmacytoid
      Dendritic Cell Neoplasm (BPDCN): CD123 and Beyond.

PMID- 29064024
TI  - Measurement of Residual Disease in Acute Myeloid Leukemia.
AB  - PURPOSE OF REVIEW: Assessment of measurable residual disease (MRD) after
      treatment can identify patients with acute myeloid leukemia (AML) that are at
      high risk of poor outcomes. However, there is no consensus yet regarding a
      standardized approach to measuring MRD that is most clinically meaningful. We
      review multiparameter flow cytometry (MFC) and reverse transcriptase polymerase
      chain reaction (RT-PCR), and discuss a framework for assessing remission MRD
      using next-generation sequencing (NGS). RECENT FINDINGS: MFC and RT-PCR may not
      fully capitalize on the major advances that have been made in characterizing the
      genetic landscape of AML, which has offered insight into the biological and
      clinical implications of clonal genetic architecture. NGS has increasingly been
      shown to provide a qualitative and quantitative assessment of MRD with
      significant prognostic implications. The assessment of clonal architecture by NGS
      may complement or extend existing approaches for MRD monitoring. Long-term serial
      monitoring of diagnostic, remission, and relapse samples with clinical
      correlation will need to be performed in order to determine the impact of various
      MRD patterns using this technique.

PMID- 29064025
TI  - Analysis of First-Year Twitter Metrics of a Rare Disease Community for Blastic
      Plasmacytoid Dendritic Cell Neoplasm (BPDCN) on Social Media: #BPDCN.
AB  - PURPOSE OF REVIEW: The use of Twitter, one of the most commonly engaged social
      media platforms in the world, is increasing among the general public. Notably,
      this trend has also been observed among those involved in the healthcare field.
      With its ability to readily connect diverse groups of stakeholders in a given
      area of interest, Twitter has become a focal point for those involved in
      increasing awareness and information exchange in orphan disease fields. Blastic
      plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic
      malignancy with generally poor long-term outcomes for adult patients and no
      standard therapeutic guidelines. Coupled with its low incidence rate, the disease
      has experienced a number of name changes over the past three decades (e.g.,
      blastic NK cell lymphoma, CD4+CD56+ hematodermic tumor), thereby historically
      resulting in difficulties in its clinico-pathologic diagnosis and treatment
      approaches. All of these factors have led to a striking gap in terms of accurate
      information available to patients and the general public. Therefore, there is an
      urgent need for the development of more venues for the dissemination of
      information, particularly online, for this rare cancer. RECENT FINDINGS: In this
      context, we began the Twitter medical community, #BPDCN, over a year ago, to help
      fill this information void. Now, completing its first year of existence, we aimed
      to analyze the metrics of Twitter use in order to better understand and to
      describe the characteristics and reach in of #BPDCN, and to determine the
      feasibility of starting and maintaining a disease-specific hashtag community in a
      particularly rare cancer.

PMID- 29064026
TI  - Models of Prognostication in Chronic Myelomonocytic Leukemia.
AB  - PURPOSE OF REVIEW: Within the group of the myelodysplastic/myeloproliferative
      overlap neoplasms of the adult age, chronic myelomonocytic leukemia (CMML) is
      characterized by an extremely variable clinical course. This review aims to cover
      over the years main advancements in the identification of CMML clinical and
      biological features associated to survival outcomes and the consequent
      development of prognostic tools for individual patient treatment decision making.
      RECENT FINDINGS: According to the last WHO classification of myeloid neoplasms,
      three subgroups of patients may be recognized on the base of percentage of blasts
      in marrow and in peripheral blood (CMML-0, CMML-1, and CMML-2), with
      corresponding decreasing life-expectations. Nonetheless, in each of the
      subgroups, prominent disparateness of biological characteristics associates to a
      large heterogeneity of clinical presentation, with very different prognostic
      implications. Recent findings indicate that the integration of clinical and
      molecular data appears to provide the most helpful prognostic information.
      Together with an orderly enlightenment for the increasing conception of specific
      disease characteristics, this review offers a comprehensive and thoughtful
      summary of the prognostic models developed over the last three decades for CMML.

PMID- 29064027
TI  - Social Media in Hematology in 2017: Dystopia, Utopia, or Somewhere In-between?
AB  - PURPOSE OF REVIEW: Social media is becoming a crucial part of our society. While
      the field of medicine has lagged behind in adopting and harnessing these
      platforms, we are now starting to see a surge in social media usage for medical
      education and scientific communication (e.g., knowledge translation, research
      collaboration, discussion, and discourse). Over the course of this review, we aim
      to update the reader on the way in which Twitter and other social media platforms
      may be used in hematology for research ideas, collaboration, and scholarly
      activity. RECENT FINDINGS: Twitter use has grown exponentially over the past
      decade and is now woven into the fabric of modern communication. It can be a
      useful tool for those who wish to engage both colleagues and the public. While
      some issues such as reporting of financial conflict of interest still need to be
      addressed, Twitter, and social medial in general, can be a powerful instrument
      for researchers, educators, patients, and advocacy groups.

PMID- 29064028
TI  - Mother-to-infant transmission of hepatitis B virus: challenges and perspectives.
AB  - Chronic hepatitis B virus (HBV) infection due to perinatal mother-to-infant
      transmission (MTIT) remains a serious global health problem. Despite passive
      active immunoprophylaxis using hepatitis B vaccination with or without hepatitis
      B immunoglobulin (HBIg), up to 8-10% of newborns still acquire HBV infection.
      Understanding the mechanisms of MTIT is essential for the interruption of HBV
      transmission. There are three possible routes of transmission: intrauterine
      transmission, transmission during delivery (intrapartum) and postnatal
      transmission through close contact or breast milk (postpartum). Overall,
      positivity for hepatitis B e antigen (HBeAg) and the high viral load of the
      mothers are the two most important risk factors related to MTIT of HBV. This
      article briefly reviews the viral factors related to MTIT of HBV and discusses
      the issues that warrant further investigation.

PMID- 29064030
TI  - Comparison of One-Stage Batch and Fed-Batch Enzymatic Hydrolysis of Pretreated
      Hardwood for the Production of Biosugar.
AB  - Fed-batch method has shown a great promise in debottlenecking the high-solid
      enzymatic hydrolysis for the commercialization of cellulosic biosugar conversion
      for biofuel/biochemical production. To further improve enzymatic hydrolysis
      efficiency at high solid loading, fed-batch methods of green liquor-pretreated
      hardwood were performed to evaluate their effects on sugar recovery by comparing
      with one-stage batch method in this study. Among all the explored conditions, the
      fed-batch at 15% consistency gave higher sugar recovery on green liquor
      pretreated hardwood compared to that of one-stage batch. By using general linear
      model analysis, the percentage of enzymatic sugar recovery in fed-batch
      consistency method (increasing consistency from the initial 10.7 to 15% at
      intervals of 24 and 48 h) was higher than that of batch hydrolysis at higher
      density of 15% consistency. Under that best fed-batch condition, the total sugar
      recovery of pretreated hardwood in enzymatic hydrolysate reached approximately
      48.41% at Cellic(r) enzyme loading of 5 filter-paper unit (FPU)/g and 58.83% at
      Cellic(r) enzyme loading of 10 FPU/g with a hydrolysis time of 96 h.

PMID- 29064031
TI  - Vaginal cystocele repair and hysteropexy in women with anterior and central
      compartment prolapse: efficacy and safety after 30 months of follow-up.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the safety and
      efficacy of vaginal native tissue repair and uterine suspension after a follow-up
      of at least 1 year. METHODS: We included all consecutive women with an anterior
      vaginal prolapse of stage II or higher and a concomitant uterine prolapse of
      stage II who underwent this surgical procedure. We considered women with a
      descensus with maximum point of less than -1 in any compartment as objectively
      cured. Overall success was defined as no prolapse symptoms, together with a
      Patient Global Impression of Improvement (PGI-I) score of 2 or less, prolapse of
      stage lower than II, and no need for other surgery. RESULTS: A total of 102
      patients underwent this surgical procedure during the study period and met all
      the inclusion criteria for statistical analysis. The mean follow-up was 31 +/-
      8.2 months; no patient was lost to follow-up. Five patients (4.9%) showed
      postoperative complications. In terms of subjective outcomes, at the last
      available follow-up, failure of this surgical procedure was seen in 2% of
      patients. The objective cure rate and the overall cure rate were the 95.1%. No
      significant deterioration in objective cure rates was observed over time (p =
      0.6). CONCLUSIONS: Vaginal repair and hysteropexy appear to be an effective and
      safe option for women with advanced uterovaginal prolapse.

PMID- 29064029
TI  - The portal hypertension syndrome: etiology, classification, relevance, and animal
      models.
AB  - BACKGROUND: Portal hypertension is a key complication of portal hypertension,
      which is responsible for the development of varices, ascites, bleeding, and
      hepatic encephalopathy, which, in turn, cause a high mortality and requirement
      for liver transplantation. AIM: This review deals with the present day state-of
      the-art preventative treatments of portal hypertension in cirrhosis according to
      disease stage. Two main disease stages are considered, compensated and
      decompensated cirrhosis, the first having good prognosis and being mostly
      asymptomatic, and the second being heralded by the appearance of bleeding or non
      bleeding complications of portal hypertension. RESULTS: The aim of treatment in
      compensated cirrhosis is preventing clinical decompensation, the more frequent
      event being ascites, followed by variceal bleeding and hepatic encephalopathy.
      Complications are mainly driven by an increase of hepatic vein pressure gradient
      (HVPG) to values >=10 mmHg (defining the presence of Clinically Significant
      Portal Hypertension, CSPH). Before CSPH, the treatment is limited to etiologic
      treatment of cirrhosis and healthy life style (abstain from alcohol,
      avoid/correct obesity...). When CSPH is present, association of a non-selective
      beta-blocker (NSBB), including carvedilol should be considered. NSBBs are
      mandatory if moderate/large varices are present. Patients should also enter a
      screening program for hepatocellular carcinoma. In decompensated patients, the
      goal is to prevent further bleeding if the only manifestation of decompensation
      was a bleeding episode, but to prevent liver transplantation and death in the
      common scenario where patients have manifested first non-bleeding complications.
      Treatment is based on the same principles (healthy life style..) associated with
      administration of NSBBs in combination if possible with endoscopic band ligation
      if there has been variceal bleeding, and complemented with simvastatin
      administration (20-40 mg per day in Child-Pugh A/B, 10-20 mg in Child C).
      Recurrence shall be treated with TIPS. TIPS might be indicated earlier in
      patients with: 1) Difficult/refractory ascites, who are not the best candidates
      for NSBBs, 2) patients having bleed under NSBBs or showing no HVPG response
      (decrease in HVPG of at least 20% of baseline or to values equal or below 12
      mmHg). Decompensated patients shall all be considered as potential candidates for
      liver transplantation. CONCLUSION: Treatment of portal hypertension has markedly
      improved in recent years. The present day therapy is based on accurate risk
      stratification according to disease stage.

PMID- 29064032
TI  - [Shoulder dislocations in elderly patients].
AB  - In contrast to shoulder dislocations in younger patients, anterior shoulder
      dislocation in the elderly is often associated with concomitant injuries to the
      rotator cuff and fractures. There is also frequent involvement of the brachial
      plexus or peripheral nerves. After closed reduction and a short period of
      immobilization, physiotherapy should be performed to restore mobility and
      strength. The evaluation of the rotator cuff is essential for further treatment
      decisions. The majority of patients are classically treated conservatively.
      Elderly patients with accompanying rotator cuff lesions and failed conservative
      therapy can benefit from a surgical intervention. Reconstructive interventions of
      the rotator cuff should be principally considered; however, some individuals may
      benefit from a reverse prosthesis in this elderly subgroup of patients. The
      challenge for the treating surgeon is to exactly define the structural injury of
      the shoulder (which may include pre-existing lesions) and to select the optimal
      treatment option.

PMID- 29064034
TI  - Immobilization of CALB on lysine-modified magnetic nanoparticles: influence of
      the immobilization protocol.
AB  - Magnetic biocatalysts offer enormous advantages over traditional ones. Their
      ability to be isolated by means of a magnet, in combination with their extensive
      reuse possibilities, makes them highly attractive and competitive from the
      commercial point of view. In this work, magnetic biocatalysts were prepared by
      immobilization of Candida antarctica Lipase B (E.C. 3.1.1.3, CALB) on magnetite
      lysine nanoparticles. Two methodologies were explored tending to find the optimal
      biocatalyst in terms of its practical implementation: I-physical adsorption of
      CALB followed by cross-linking, and II-covalent coupling of the lipase on the
      nanoparticles surface. Both procedures involved the use of glutaraldehyde (GLUT)
      as cross-linker or coupling agent, respectively. A range of GLUT concentrations
      was evaluated in method I and the optimum one, in terms of efficiency and
      operational stability, was chosen to induce the covalent linkage CALB-support in
      method II. The chosen test reaction was solvent-free ethyl oleate synthesis.
      Method I produced operationally unstable catalysts that deactivated totally in
      four to six cycles. On the other hand, covalently attached CALB (method II)
      preserved 60% of its initial activity after eight cycles and also retained 90% of
      its initial activity along 6 weeks in storage. CALB immobilization by covalent
      linkage using controlled GLUT concentration appears as the optimum methodology to
      asses efficient and stable biocatalysts. The materials prepared within this work
      may be competitive with commercially available biocatalysts.

PMID- 29064035
TI  - [Patient-sharing networks : New approaches in the analysis and transformation of
      geographic variation in healthcare].
AB  - The analysis of geographic variations has spurred arguments that area of
      residence determines access to and quality of healthcare. In this paper we argue
      that unwarranted geographic variations can be traced back to actions of
      individual patients and their healthcare providers (doctors, hospitals). These
      actors interact in a complicated web of shared responsibilities. Designing
      effective interventions to reduce unwarranted geographic variations may therefore
      depend on methods to identify these interactions and communities of providers
      with a shared accountability. In the US, Canada, and Germany, routine data have
      been used to identify self-organized informal or virtual networks of physicians
      and hospitals, so-called patient-sharing networks (PSNs). This is an emerging
      field of analysis. We attempt to provide a brief report on the state of work in
      progress. It can be shown that variation between PSNs in a given area is
      effectively greater than variation between regions. While this suggests that
      reducing unwarranted variation needs to start at the level of PSN, methods to
      identify PSNs still vary widely. We compare epidemiological approaches and
      approaches based on graph theory and social network analysis. We also present
      some preliminary findings of exploratory analyses based on comprehensive claims
      data of physician practices in Germany. Defining PSNs based on usual provider
      relationships helps to create distinctive patient populations while PSNs may not
      be mutually exclusive. Social network analysis, on the other hand, appears better
      equipped to differentiate between provider communities with stronger and weaker
      ties; it does not yield distinctive patient populations. To achieve
      accountability and to support change management, analytic methods to describe
      PSNs still need refinement. There are first projects in Germany which use PSNs as
      an intervention platform in order to achieve improved cooperation and reduce
      unwarranted variation in their care processes.

PMID- 29064033
TI  - Association of maternal exposures with adiposity at age 4/5 years in white
      British and Pakistani children: findings from the Born in Bradford study.
AB  - AIMS/HYPOTHESIS: There is evidence that, from birth, South Asians are fatter, for
      a given body mass, than Europeans. The role of developmental overnutrition
      related to maternal adiposity and circulating glucose in these ethnic differences
      is unclear. Our aim was to compare associations of maternal gestational adiposity
      and glucose with adiposity at age 4/5 years in white British and Pakistani
      children. METHODS: Born in Bradford is a prospective study of children born
      between 2007 and 2010 in Bradford, UK. Mothers completed an OGTT at 27-28 weeks
      of gestation. We examined associations between maternal gestational BMI, fasting
      glucose, post-load glucose and diabetes (GDM) and offspring height, weight, BMI
      and subscapular skinfold (SSF) and triceps skinfold (TSF) thickness at age 4/5
      years, using data from 6060 mother-offspring pairs (2717 [44.8%] white British
      and 3343 [55.2%] Pakistani). RESULTS: Pakistani mothers had lower BMI and higher
      fasting and post-load glucose and were twice as likely to have GDM (defined using
      modified WHO criteria) than white British women (15.8% vs 6.9%). Pakistani
      children were taller and had lower BMI than white British children; they had
      similar SSF and lower TSF. Maternal BMI was positively associated with the
      adiposity of offspring in both ethnic groups, with some evidence of stronger
      associations in Pakistani mother-offspring pairs. For example, the difference in
      adjusted mean BMI per 1 kg/m2 greater maternal BMI was 0.07 kg/m2 (95% CI 0.05,
      0.08) and 0.10 kg/m2 (95% CI 0.09. 0.11) in white British and Pakistani children,
      respectively, with equivalent results for SSF being 0.07 mm (95% CI 0.05, 0.08)
      and 0.09 mm (95% CI 0.08. 0.11) (p for ethnic difference < 0.03 for both). There
      was no strong evidence of association of fasting and post-load glucose, or GDM,
      with outcomes in either group. CONCLUSIONS/INTERPRETATION: At age 4/5 years,
      Pakistani children are taller and lighter than white British children. While
      maternal BMI is positively associated with offspring adiposity, gestational
      glycaemia is not clearly related to offspring adiposity in either ethnic group.

PMID- 29064036
TI  - Comparative long-term trend analysis of daily weather conditions with daily
      pollen concentrations in Brussels, Belgium.
AB  - A clear rise in seasonal and annual temperatures, a gradual increase of total
      radiation, and a relative trend of change in seasonal precipitation have been
      observed for the last four decades in Brussels (Belgium). These local
      modifications may have a direct and indirect public health impact by altering the
      timing and intensity of allergenic pollen seasons. In this study, we assessed the
      statistical correlations (Spearman's test) between pollen concentration and
      meteorological conditions by using long-term daily datasets of 11 pollen types (8
      trees and 3 herbaceous plants) and 10 meteorological parameters observed in
      Brussels between 1982 and 2015. Furthermore, we analyzed the rate of change in
      the annual cycle of the same selected pollen types by the Mann-Kendall test. We
      revealed an overall trend of increase in daily airborne tree pollen (except for
      the European beech tree) and an overall trend of decrease in daily airborne
      pollen from herbaceous plants (except for Urticaceae). These results revealed an
      earlier onset of the flowering period for birch, oak, ash, plane, grasses, and
      Urticaceae. Finally, the rates of change in pollen annual cycles were shown to be
      associated with the rates of change in the annual cycles of several
      meteorological parameters such as temperature, radiation, humidity, and rainfall.

PMID- 29064038
TI  - Hypofractionated high-energy proton-beam irradiation is an alternative treatment
      for WHO grade I meningiomas.
AB  - BACKGROUND: Radiation treatment is commonly employed in the treatment of
      meningiomas. The aim of this study was to evaluate the effectiveness and safety
      of hypofractionated high-energy proton therapy as adjuvant or primary treatment
      for WHO grade I meningiomas. METHOD: A total of 170 patients who received
      irradiation with protons for grade I meningiomas between 1994 and 2007 were
      included in the study. The majority of the tumours were located at the skull base
      (n = 155). Eighty-four patients were treated post subtotal resection, 42 at
      tumour relapse and 44 with upfront radiotherapy after diagnosis based on the
      typical radiological image. Irradiation was given in a hypofractionated fashion
      (3-8 fractions, usually 5 or 6 Gy) with a mean dose of 21.9 Gy (range, 14-46 Gy).
      All patients were planned for follow-up with clinical controls and magnetic
      resonance imaging scans at 6 months and 1, 2, 3, 5, 7 and 10 years after
      treatment. The median follow-up time was 84 months. Age, gender, tumour location,
      Simpson resection grade and target volume were assessed as possible prognostic
      factors for post-irradiation tumour progression and radiation related
      complications. RESULTS: The actuarial 5- and 10-year progression-free survival
      rates were 93% and 85% respectively. Overall mortality rate was 13.5%, while
      disease-specific mortality was 1.7% (3/170 patients). Older patients and patients
      with tumours located in the middle cranial fossa had a lower risk for tumour
      progression. Radiation-related complications were seen in 16 patients (9.4%),
      with pituitary insufficiency being the most common. Tumour location in the
      anterior cranial fossa was the only factor that significantly increased the risk
      of complications. CONCLUSIONS: Hypofractionated proton-beam radiation therapy may
      be used particularly in the treatment of larger World Health Organisation grade I
      meningiomas not amenable to total surgical resection. Treatment is associated
      with high rates of long-term tumour growth control and acceptable risk for
      complications.

PMID- 29064039
TI  - Posterior long segment stabilization of an adjacent insufficiency fracture.

PMID- 29064040
TI  - A systematic review of prognostic factors predicting survival in patients with
      spinal bone metastases.
AB  - PURPOSE: For the selection of treatment in patients with spinal bone metastases
      (SBM), survival estimation plays a crucial role to avoid over- and under
      treatment. To aid clinicians in this difficult task, several prediction models
      have been developed, consisting of many different risk factors. The aim of this
      systematic review was to identify prognostic factors that are associated with
      survival in patients with SBM to support development of predictive models.
      METHODS: A systematic review was performed with focus on prognostic factors
      associated with survival in patients with SBM. Two reviewers independently
      selected studies for inclusion and assessed the risk of bias. A level of evidence
      synthesis was performed for each prognostic factor. Inter-observer agreement for
      the risk of bias assessment was determined by the kappa-statistic. RESULTS: After
      screening, 142 full-text articles were obtained, of which 22 met the eligibility
      criteria. A total of 43 different prognostic factors were investigated in the
      included studies, of which 17 were relevant to pre-treatment survival estimation.
      The prognostic factors most frequently associated with survival were the primary
      tumor and the performance status. The prognostic factors most frequently not
      associated with survival were age, gender, number and location of the SBM and the
      presence of a pathologic fracture. CONCLUSIONS: Prognostication for patients with
      SBM should be based on an accurate primary tumor classification, combined with a
      performance score. The benefit of adding other prognostic factors is doubtful.

PMID- 29064041
TI  - Does Cardiac Resynchronization Therapy Benefit Patients with Non-Left Bundle
      Branch Block Prolonged QRS Patterns?
AB  - PURPOSE OF REVIEW: We sought to assess the utility of CRT in patients with non
      LBBB. RECENT FINDINGS: CRT has an established role as a device-based therapy for
      patients with HF with systolic dysfunction and intraventricular conduction
      disease, specifically LBBB. In modern practice, the use of CRT in non-LBBB
      patients remains controversial, with high rates of non-response for CRT in
      patients with RBBB, in particular. Recent studies have identified sub-populations
      of non-LBBB patients that respond to resynchronization, such as those with
      prolonged PR intervals (>= 230 ms), with RBBB and concomitant left-sided delay
      and those with significant burden of right ventricular pacing. As technology has
      advanced to allow for detailed mapping of LV electrical and mechanical function,
      benefits have been found with placement of LV leads utilizing intra-procedural
      mapping to target areas of greatest electrical activation delay or mechanical
      dyssynchrony, leading to more widespread benefit through the more specific
      application of CRT.

PMID- 29064042
TI  - Treatment-Induced Neuropathy of Diabetes.
AB  - PURPOSE OF REVIEW: Treatment-induced neuropathy of diabetes (TIND) is an under
      recognized iatrogenic painful sensory and autonomic neuropathy. This review
      highlights the clinical symptoms and signs, raises awareness of the cause, and
      provides education about prevention of TIND. RECENT FINDINGS: TIND may be
      triggered by a rapid decline in the blood glucose levels following the use of
      insulin, oral hypoglycemic medications, or even diet only to control diabetes.
      This may be seen in up to 10% of patients with diabetic neuropathy and has the
      potential for significant long-term complications that could be avoided through
      careful disease management. Based on the available evidence, a decrease in the
      glycosylated hemoglobin A1C of more than 3 points in 3 months in individuals with
      chronic hyperglycemia increases the risk of developing TIND. TIND is more common
      than previously suspected, and is tied to rates of glycemic control. Slower
      changes to glucose control are suggested, although there is no prospective data
      on disease prevention. Future research is necessary to guide treatment
      recommendations.

PMID- 29064043
TI  - A case of regional migratory osteoporosis.
AB  - We present the case of a middle-aged man with three episodes of regional
      migratory osteoporosis of the lower extremities occurring over a period of 8
      years. Symptoms included a sudden onset of unilateral bone and joint pain. After
      initiation of pamidronate treatment, symptoms improved significantly. Regional
      migratory osteoporosis is a rare, but probably underdiagnosed condition with an
      unclear etiology. This case illustrates the importance of recognition of the
      disease in order to inform the patient, start treatment, and prevent unnecessary
      invasive procedures. Although in literature, not much is reported about treatment
      strategies, our patient was successfully treated with pamidronate after failure
      of oral bisphosphonates.

PMID- 29064044
TI  - Management of Elective Surgery and Emergent Bleeding with Direct Oral
      Anticoagulants.
AB  - PURPOSE OF REVIEW: The purpose of this review was to offer practical management
      strategies for when patients receiving direct oral anticoagulants require
      elective surgery or present with bleeding complications. RECENT FINDINGS:
      Clinical practice guidelines are now available on the timing of periprocedural
      interruption of treatment with the newer direct oral anticoagulants based on
      their pharmacodynamics and pharmacokinetics and based on findings from cohort
      studies and clinical trials. An antibody that reverses the effects of dabigatran
      is now available, and a factor Xa decoy is being developed as an antidote to
      apixaban, betrixaban, edoxaban, and rivaroxaban. The timing of interruption of
      direct oral anticoagulants for elective surgery is based on multiple factors,
      including pharmacologic properties and interactions, the patient's renal
      function, and the type of planned surgery. There is little role for low-molecular
      weight heparin bridging. Idarucizumab is the treatment of choice for dabigatran
      related life-threatening bleeding, while andexanet alfa is being developed to
      reverse factor Xa inhibitors.

PMID- 29064045
TI  - Long-term outcome of catheter ablation and other form of therapy for electrical
      storm in patients with implantable cardioverter-defibrillators.
AB  - PURPOSE: Radiofrequency catheter ablation (RFCA) for electrical storm (ES) has
      become a widely used therapeutic method. Its effectiveness in comparison to other
      forms of ES treatment is however uncertain. METHODS: This single-centre
      retrospective study investigated the long-term clinical outcome after RFCA for ES
      and compared long-time effects of ablation to other forms of treatment. The study
      population consisted of 70 consecutive patients hospitalised between January 2010
      and June 2015 due to ES. Patients were recruited for the study if the following
      criteria were fulfilled: first ES caused by ventricular tachycardia (VT) or
      ventricular fibrillation (VF), implanted cardioverter defibrillator or cardiac
      resynchronisation therapy device and left ventricular ejection fraction < 50%.
      The follow-up data on VT/ES recurrence was obtained from pacemaker/implanted
      cardioverter defibrillator memory. Data on all-cause mortality was collected
      during outpatient visits or by telephone contact. RESULTS: Of the 70 patients
      enrolled, 28 (40%) were treated with RFCA (group A) and 42 (60%) received other
      forms of treatment for ES (group B). During a mean (+/-SD) 864 (629) days of
      follow-up, death occurred in 4 (14.3%) patients in the ablation group and in 16
      (38.1%) patients treated with other methods [p = 0.03]. There was no significant
      between-group difference in VT/VF and ES recurrence. Statistical analysis
      revealed that the presence of cardiac resynchronisation therapy device during ES,
      stroke and/or transient ischaemic attack and lower baseline hematocrit level were
      the multivariate predictors of all-cause mortality. CONCLUSIONS: In patients
      treated with RFCA for ES, all-cause mortality was significantly lower compared to
      the group treated with other methods.

PMID- 29064046
TI  - HLA, infections and inflammation in early stages of atherosclerosis in children
      with type 1 diabetes.
AB  - AIMS: This prospective study focuses on risk factors for arterial damage in
      children with type 1 diabetes (T1D). METHODS: Eighty children and adolescents
      with T1D were investigated twice, approximately 2 years apart, for carotid artery
      intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation
      (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)
      8. All subjects were genotyped for HLA. The number of respiratory tract
      infections (RTI) during the past year was obtained by a questionnaire in 56
      patients. RESULTS: cIMT progression, defined as percentage (%) change of cIMT
      from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r =
      - 0.3; n = 62) and FMD (p = 0.03, r = - 0.3; n = 47). In multivariate analysis,
      RTI frequency correlated significantly with cIMT progression irrespective of age,
      diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided
      in relation to RTI, the association of DQ2/8 with cIMT progression remained
      significant in patients with over three infections/year (p = 0.04, r = 0.3).
      During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed
      significantly higher levels of plasma MMP-8 than the non-DQ2/8 group.
      CONCLUSIONS: The diabetes-risk genotype DQ2/8 and systemic inflammation
      contribute to pro-atherosclerotic vascular changes in children and adolescents
      with T1D.

PMID- 29064048
TI  - Patient-physician relationship in specific cultural settings.

PMID- 29064047
TI  - Pancreatic imaging using an antibody fragment targeting the zinc transporter type
      8: a direct comparison with radio-iodinated Exendin-4.
AB  - AIM: The zinc transporter 8 (ZnT8) has been suggested as a suitable target for
      non-invasive visualization of the functional pancreatic beta cell mass, due to
      both its pancreatic beta cell restricted expression and tight involvement in
      insulin secretion. METHODS: In order to examine the potential of ZnT8 as a
      surrogate target for beta cell mass, we performed mRNA transcription analysis in
      pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was
      radiolabeled with iodine-125, and evaluated by in vitro autoradiography in
      insulinoma and pancreas as well as by in vivo biodistribution. The evaluation was
      performed in a direct comparison with radio-iodinated Exendin-4. RESULTS:
      Transcription of the ZnT8 mRNA was higher in islets of Langerhans compared to
      exocrine tissue. Ab31 targeted ZnT8 in the cytosol and on the plasma membrane
      with 108 nM affinity. Ab31 was successfully radiolabeled with iodine-125 with
      high yield and > 95% purity. [125I]Ab31 binding to insulinoma and pancreas was
      higher than for [125I]Exendin-4, but could only by partially competed away by 200
      nM Ab31 in excess. The in vivo uptake of [125I]Ab31 was higher than [125I]Exendin
      4 in most tissues, mainly due to slower clearance from blood. CONCLUSIONS: We
      report a first-in-class ZnT8 imaging ligand for pancreatic imaging. Development
      with respect to ligand miniaturization and radionuclide selection is required for
      further progress. Transcription analysis indicates ZnT8 as a suitable target for
      visualization of the human endocrine pancreas.

PMID- 29064049
TI  - Phenolic Glycosides in Populus tremuloides and their Effects on Long-Term
      Ungulate Browsing.
AB  - In the aspen-grassland ecotone of Riding Mountain, Manitoba, lightly browsed
      vigorous clones of trembling aspen (Populus tremuloides Michx.) occur in close
      proximity to heavily browsed dieback clones. This study examines whether
      intraspecific variation in the production of phenolic glycosides is correlated
      with this strong dichotomy in clonal vigor. Individual clones were sampled over
      four years at three sites located along a gradient of increasing soil moisture
      stress. At each site, eight aspen clones of similar size and age were sampled:
      four vigorous and four dieback clones (total of 24 individual clones). The
      severity of wapiti (elk) browsing was assessed as the ratio of browse-damaged to
      total branches per aspen ramet. Statistically significant differences in foliar
      concentrations of the phenolic glycosides salicortin and tremulacin were observed
      between vigorous and dieback clones: a mean of 14.8% dry mass for lightly browsed
      (vigorous) clones, versus just 7.0% for heavily browsed (dieback) clones. Mean
      concentrations of foliar phenolics were also significantly greater in more
      moisture-stressed sites. These results demonstrate that the strong dichotomy in
      clonal vigor (vigorous versus dieback clones) is associated with large
      differences in phenolic glycoside production. Vigorous clone ramets produce high
      amounts of phenolic glycosides and have low levels of herbivore browsing and low
      mortality rates, whereas dieback clone ramets have low amounts of phenolic
      glycosides and much higher herbivore browsing and mortality rates. This suggests
      that intraspecific variation in phenolic glycosides in trembling aspen is an
      important predisposing factor leading to ramet mortality, and by extension to the
      decline of aspen clones.

PMID- 29064052
TI  - Bidimensional perovskite systems for spintronic applications.
AB  - The half-metallic behavior of the perovskite Sr2FeMoO6 (SFMO) suggests that this
      material could be used in spintronic applications. Indeed, SFMO could be an
      attractive material for multiple applications due to the possibility that its
      electronic properties could be changed by modifying its spatial confinement or
      the relative contents of its constituent transition metals. However, there are no
      reports of theoretical studies on the properties of confined SFMOs with different
      transition metal contents. In this work, we studied the electronic properties of
      SFMO slabs using spin-polarized first-principles density functional theory along
      with the Hubbard-corrected local density approximation and a supercell scheme. We
      modeled three insulated SFMO slabs with Fe:Mo atomic ratios of 1:1, 1:0, and 0:1;
      all with free surfaces parallel to the (001) crystal plane. The results show that
      the half-metallicity of the SFMO is lost upon confinement and the material
      becomes a conductor, regardless of the ratio of Fe to Mo. It was also observed
      that the magnetic moment of the slab is strongly influenced by the oxygen atoms.
      These results could prove useful in attempts to apply SFMOs in fields other than
      spintronics. Graphical abstract Losing the metallic behaviour: density of states
      changes, around the Fermi level, due to the Fe/Mo ratio for bidimensional
      perovskite systems.

PMID- 29064051
TI  - A Brief Review on Fluorescent Copper Sensor Based on Conjugated Organic Dyes.
AB  - The design and development of the fluorescence reporting molecules for the trace
      recognition of the metallic ions in the aqueous, mixed organic aqueous media,
      environmental specimen, living things e.g., body fluids, serum, urine etc is the
      evergreen research area. Among several methodologies utilized for these purposes,
      the fluorescent techniques have wonderful impact in the era of metal sensor
      development due to their acclamatory features of non-invasive detection process
      and appreciable sensitivity. The utilization of small organic molecules for the
      sensation of metallic ions through the fluorescent techniques harvested the
      wonderful results having some interesting features of chromogenic response on
      metal binding, robustness in the preparation and applicability to establish the
      metallic accumulation level inside the live cells via bioimaging studies. The
      detailed knowledge and background about the several reported chemosening
      strategies have the utmost importance in order to understand or to design the
      novel molecules for metal sensing purposes. The objective of the presents review
      was to compile the best ever used copper sensing strategies via fluorescent means
      in the running decade. We have summarized the values of optical positions of the
      spectral lines, spectral shifting upon metal binding,
      binding/association/dissociation constants, chromogenic changes in the reaction
      mixture, proposed complexation mechanism of the ligand with the copper, ligand
      sensitivities toward the copper recognition, binding stoichiometries and the
      detailed bioimaging results where applicable.

PMID- 29064053
TI  - Correlation of Circulating CD64+/CD163+ Monocyte Ratio and stroma/peri-tumoral
      CD163+ Monocyte Density with Human Papillomavirus Infected Cervical Lesion
      Severity.
AB  - HPV infected cervical cells secrete mediators that are gradually changed and have
      influence on infiltrating M2 phenotypic monocytes in cervical lesions. However,
      profiles of circulating immune cells in women with cervical lesions and M2
      phenotypic monocyte activity in HPV infected cervical lesions are limited. This
      study aimed to investigate circulating monocyte populations correlated with M2
      phenotype density and its activity in HPV infected cervical lesions. HPV DNA was
      investigated in cervical tissues using PCR. High risk HPV E6/E7 mRNA was detected
      using in situ hybridization. CD163 immunohistochemical staining was performed for
      M2 macrophage. CD163 and Arg1 mRNA expression were detected using real-time PCR.
      Circulating monocyte subpopulations were analyzed using flow cytometry. CD163 and
      Arg1 mRNA expression were increased according to cervical lesion severity and
      corresponding with density of M2 macrophage in HSIL and SCC in stroma and peri
      tumoral areas. Additionally, the relationship between M2 macrophage infiltration
      and high risk HPV E6/E7 mRNA expression was found and corresponded with cervical
      lesion severity. Circulating CD14+CD16+ and CD14+CD163+ monocytes were elevated
      in No-SIL and cervical lesions. Interestingly, CD14+CD64+ monocyte was greatly
      elevated in HSIL and SCC, whereas intracellular IL-10+ monocytes were not
      significantly different between cervical lesions. The correlation between
      increasing ratio of circulating CD64+/CD163+ monocyte and density of infiltrating
      CD163+ monocytes was associated with severity of HPV infected cervical lesions.
      The elevated circulating CD64+/CD163+ monocyte ratio correlates to severity of
      HPV infected cervical lesions and might be a prognostic marker in cervical cancer
      progression.

PMID- 29064055
TI  - Towards Rectifying Performance at the Molecular Scale.
AB  - Molecular diode, proposed by Mark Ratner and Arieh Aviram in 1974, is the first
      single-molecule device investigated in molecular electronics. As a fundamental
      device in an electric circuit, molecular diode has attracted an enduring and
      extensive focus during the past decades. In this review, the theoretical and
      experimental progresses of both charge-based and spin-based molecular diodes are
      summarized. For the charge-based molecular diodes, the rectifying properties
      originated from asymmetric molecules including D-sigma-A, D-pi-A, D-A, and sigma
      pi type compounds, asymmetric electrodes, asymmetric nanoribbons, and their
      combination are analyzed. Correspondingly, the rectification mechanisms are
      discussed in detail. Furthermore, a series of strategies for modulating
      rectification performance is figured out. Discussion on concept of molecular spin
      diode is also involved based on a magnetic co-oligomer. At the same time, the
      intrinsic mechanism as well as the modulation of the spin-current rectification
      performance is introduced. Finally, several crucial issues that need to be
      addressed in the future are given.

PMID- 29064054
TI  - HistoScanningTM to Detect and Characterize Prostate Cancer-a Review of Existing
      Literature.
AB  - PURPOSE OF REVIEW: The widely acknowledged limitations of the standard prostate
      cancer (PCa) diagnostic paradigm have provided an impetus to explore novel
      imaging modalities to diagnose, localize, and risk stratify PCa. As the body of
      literature focused on HistoScanningTM(HS) grows, there is need for a
      comprehensive review of the clinical efficacy of this technology. RECENT
      FINDINGS: Eighteen original, English language articles were found to adequately
      study the use of HistoScanningTM for prostate cancer diagnosis in the clinical
      setting. The articles were found by conducting a bibliographic search of PubMed
      in April 2017 in addition to utilizing references. The studies are divided into
      four groups based on study design. Study methods and quantitative data are
      summarized for each of the relevant articles. The results are synthesized to
      evaluate the utility of HistoScanningTM for the purpose of diagnosing PCa.
      Despite the promise of early pilot studies, there is a lack of consistent results
      across a number of further investigations of HistoScanningTM. This becomes
      increasingly evident as study size increases. As various other modern diagnostic
      modalities continue to develop, the future of HistoScanningTM, both alone and in
      conjunction with these technologies, remains unclear.

PMID- 29064056
TI  - Isolation, Identification of Lactobacillus mucosae AN1 and its Antilisterial
      Peptide Purification and Characterization.
AB  - Lactobacillus mucosae strain AN1 isolated from sheep milk and characterized for
      its probiotic suitability. In vitro evaluation of critical gut endurance
      properties of this strain were assessed by different screening methods such as
      bile salt, gastric acid, lysozyme tolerance assays, hemolytic, cholesterol
      reduction properties, and HT-29 cell line adhesion assay. Antibacterial peptide
      from this strain was purified using ammonium sulphate precipitation, gel
      filtration chromatography and reverse-phase HPLC. The molecular mass of peptides
      was determined by Tricine-SDS-PAGE and confirmed by matrix-assisted laser
      desorption ionization-time of flight mass spectroscopy (MALDI-TOF-MS). Purified
      peptide was named as AN1 having a molecular mass of 10.66 kDa. Helical structures
      of peptide were determined using circular dichroism spectroscopy. Stability of
      peptide AN1 towards different parameters such as pH, temperature, organic
      solvents, proteolytic, and glycolytic enzymes was also analyzed.

PMID- 29064057
TI  - Antiaflatoxigenic Potential of Cell-Free Supernatant from Lactobacillus plantarum
      MYS44 Against Aspergillus parasiticus.
AB  - The study aims to evaluate the cell-free supernatant (CFS) from Lactobacillus
      plantarum strain MYS44 against the growth and aflatoxin production by Aspergillus
      parasiticus MTCC 411. Standard in vitro techniques revealed the potential
      antifungal activity of CFS of LpMYS44. In poison food technique, it was observed
      that 6% CFS of LpMYS44 retarded maximum growth. The inhibition of A. parasiticus
      on peanuts confirmed the ability of CFS of LpMYS44 for biopreservation. Further,
      CFS of LpMYS44 was purified by chromatography and analyzed by GC-MS. The major
      antifungal compounds were oleic acid, octanoic acid, butanamide, and decanoic
      acid derivatives. Twofold concentrated 80 MUL of CFS was found to be minimum
      inhibitory concentration (MIC) of CFS of LpMYS44. CFS of LpMYS44 suppressed the
      germination and growth of the spores of A. parasiticus. Microscopic observation
      showed that CFS of LpMYS44 severely affected the hyphal wall of A. parasiticus by
      the leakage of cytoplasmic content leading to complete destruction. Acidic
      condition is favorable for CFS of LpMYS44 activity. In poultry feed sample, CFS
      of LpMYS44 reduced the aflatoxin B1 content by 34.2%, reflecting its potentiality
      to use as detoxification agent. The multiple antifungal components in CFS of
      LpMYS44 exhibited antifungal properties against aflatoxigenic A. parasiticus
      resulted in causing overall morphological changes. Furthermore, we also observed
      the biopreservative ability of CFS of LpMYS44 against A. parasiticus and AFB1
      reduction in for poultry feed. This study makes a contribution to using CFS of
      LpMYS44 and their applications in food and feed as pretreatment against
      aflatoxigenic A. parasiticus to reduce or eliminate AFB1 and maybe other
      aflatoxins, produced by other Aspergillus spp.

PMID- 29064060
TI  - Regulation of Gene and Protein Expression in the Lyme Disease Spirochete.
AB  - The infectious cycle of Borrelia burgdorferi necessitates persistent infection of
      both vertebrates and ticks, and efficient means of transmission between those two
      very different types of hosts. The Lyme disease spirochete has evolved mechanisms
      to sense its location in the infectious cycle, and use that information to
      control production of the proteins and other factors required for each step.
      Numerous components of borrelial regulatory pathways have been characterized to
      date. Their effects are being pieced together, thereby providing glimpses into a
      complex web of cooperative and antagonistic interactions. In this chapter, we
      present a broad overview of B. burgdorferi gene and protein regulation during the
      natural infectious cycle, discussions of culture-based methods for elucidating
      regulatory mechanisms, and summaries of many of the known regulatory proteins and
      small molecules. We also highlight areas that are in need of substantially more
      research.

PMID- 29064058
TI  - Growth Performance, Hemato-Immunological Responses, and Digestive Enzyme
      Activities in Silvery-Black Porgy (Sparidentex hasta) Fed Dietary Bovine
      Lactoferrin.
AB  - An 8-week study was conducted to evaluate three different diets supplemented with
      bovine lactoferrin (LF) at 0 (control), 800, and 1200 mg LF kg-1 diet on somatic
      growth, hemato-immunological parameters, antioxidant status, and digestive enzyme
      activities in silvery-black porgy (Sparidentex hasta) juveniles. Fish fed the 800
      mg LF kg-1 diet had higher growth performance and feed utilization parameters
      than the other groups. Hematological and liver antioxidant parameters were not
      affected by dietary LF supplementation. Fish fed the 800 mg LF kg-1 diet had
      higher plasma lysozyme activity values than the other groups. Total protease
      activity was higher in fish fed LF-supplemented diets than the control group.
      Results indicated that diet supplemented with 800 mg kg-1 for 8 weeks enhanced
      somatic growth performance, lysozyme activity, and proteolytic digestive enzyme
      activities in S. hasta, as well as improving feed efficiency parameters like the
      protein efficiency and feed conversion ratios.

PMID- 29064059
TI  - Spiking resonances in models with the same slow resonant and fast amplifying
      currents but different subthreshold dynamic properties.
AB  - The generation of spiking resonances in neurons (preferred spiking responses to
      oscillatory inputs) requires the interplay of the intrinsic ionic currents that
      operate at the subthreshold voltage level and the spiking mechanisms.
      Combinations of the same types of ionic currents in different parameter regimes
      may give rise to different types of nonlinearities in the voltage equation (e.g.,
      parabolic- and cubic-like), generating subthreshold (membrane potential)
      oscillations patterns with different properties. These nonlinearities are not
      apparent in the model equations, but can be uncovered by plotting the voltage
      nullclines in the phase-plane diagram. We investigate the spiking resonant
      properties of conductance-based models that are biophysically equivalent at the
      subthreshold level (same ionic currents), but dynamically different (parabolic-
      and cubic-like voltage nullclines). As a case study we consider a model having a
      persistent sodium and a hyperpolarization-activated (h-) currents, which exhibits
      subthreshold resonance in the theta frequency band. We unfold the concept of
      spiking resonance into evoked and output spiking resonance. The former focuses on
      the input frequencies that are able to generate spikes, while the latter focuses
      on the output spiking frequencies regardless of the input frequency that
      generated these spikes. A cell can exhibit one or both types of resonances. We
      also measure spiking phasonance, which is an extension of subthreshold phasonance
      (zero-phase-shift response to oscillatory inputs) to the spiking regime. The
      subthreshold resonant properties of both types of models are communicated to the
      spiking regime for low enough input amplitudes as the voltage response for the
      subthreshold resonant frequency band raises above threshold. For higher input
      amplitudes evoked spiking resonance is no longer present in these models, but
      output spiking resonance is present primarily in the parabolic-like model due to
      a cycle skipping mechanism (involving mixed-mode oscillations), while the cubic
      like model shows a better 1:1 entrainment. We use dynamical systems tools to
      explain the underlying mechanisms and the mechanistic differences between the
      resonance types. Our results demonstrate that the effective time scales that
      operate at the subthreshold regime to generate intrinsic subthreshold
      oscillations, mixed-mode oscillations and subthreshold resonance do not
      necessarily determine the existence of a preferred spiking response to
      oscillatory inputs in the same frequency band. The results discussed in this
      paper highlight both the complexity of the suprathreshold responses to
      oscillatory inputs in neurons having resonant and amplifying currents with
      different time scales and the fact that the identity of the participating ionic
      currents is not enough to predict the resulting patterns, but additional dynamic
      information, captured by the geometric properties of the phase-space diagram, is
      needed.

PMID- 29064062
TI  - Assessing robustness of designs for random effects parameters for nonlinear mixed
      effects models.
AB  - Optimal designs for nonlinear models are dependent on the choice of parameter
      values. Various methods have been proposed to provide designs that are robust to
      uncertainty in the prior choice of parameter values. These methods are generally
      based on estimating the expectation of the determinant (or a transformation of
      the determinant) of the information matrix over the prior distribution of the
      parameter values. For high dimensional models this can be computationally
      challenging. For nonlinear mixed-effects models the question arises as to the
      importance of accounting for uncertainty in the prior value of the variances of
      the random effects parameters. In this work we explore the influence of the
      variance of the random effects parameters on the optimal design. We find that the
      method for approximating the expectation and variance of the likelihood is of
      potential importance for considering the influence of random effects. The most
      common approximation to the likelihood, based on a first-order Taylor series
      approximation, yields designs that are relatively insensitive to the prior value
      of the variance of the random effects parameters and under these conditions it
      appears to be sufficient to consider uncertainty on the fixed-effects parameters
      only.

PMID- 29064061
TI  - Molecular Characterization and Antifungal Susceptibility Testing of Sequentially
      Obtained Clinical Cryptococcus deneoformans and Cryptococcus neoformans Isolates
      from Ljubljana, Slovenia.
AB  - AIM: To retrospectively investigate the epidemiology of cryptococcosis in
      Ljubljana, Slovenia. METHODOLOGY: Forty-six sequentially obtained isolates from
      19 patients were subjected to amplified fragment length polymorphism (AFLP)
      genotyping, microsatellite typing, mating- and serotype PCRs and antifungal
      susceptibility testing. RESULTS: Majority of the isolates were Cryptococcus
      deneoformans (n = 29/46; 63%) followed by Cryptococcus neoformans (n = 16/46;
      34.8%) and their interspecies hybrid (n = 1/46; 2.2%). Mating-type alpha was
      predominant, two mating-type a C. deneoformans isolates and one mating-type
      a/alpha isolate were observed. Several mixed infections were found by
      microsatellite typing; one patient had a persisting C. deneoformans infection for
      > 2.5 years. For C. deneoformans, the in vitro antifungal MIC90 and
      susceptibility ranges were for amphotericin B 0.25 ug/ml (0.031-0.25 ug/ml), 5
      fluorocytosine 0.25 ug/ml (0.063-4 ug/ml), fluconazole 8 ug/ml (0.5-16 ug/ml),
      voriconazole 0.063 ug/ml (0.008-0.125 ug/ml), posaconazole 0.063 ug/ml (0.008
      0.063 ug/ml) and itraconazole 0.063 ug/ml (0.031-0.125 ug/ml). For C. neoformans,
      these values were for amphotericin B 0.25 ug/ml (0.063-0.5 ug/ml), 5
      fluorocytosine 1 ug/ml (0.063-1 ug/ml), fluconazole 16 ug/ml (0.5-64 ug/ml),
      voriconazole 0.125 ug/ml (0.008-0.25 ug/ml), posaconazole 0.063 ug/ml (0.008
      0.063 ug/ml) and itraconazole 0.063 ug/ml (0.031-0.125 ug/ml). CONCLUSIONS:
      Majority of the cases were caused by C. deneoformans; mating-type alpha was
      predominant. Several mixed infections were identified by AFLP genotyping and
      microsatellite typing. Despite antifungal therapy, a cryptococcal isolate could
      persist for years. Voriconazole, itraconazole and posaconazole were the most
      potent antifungal drugs.

PMID- 29064063
TI  - Production, performance, slaughter characteristics, and meat quality of Ziwuling
      wild crossbred pigs.
AB  - Wild boars, because of their large size and ability to survive adverse
      conditions, are usually used to cross with domestic breeds to improve the quality
      of domesticated pigs. This study aimed to investigate the growth performance,
      slaughter performance, and meat quality of Ziwuling crossbred pigs. Crossbred
      pigs in four groups (n = 8 per group, 4 boars and 4 sows, all aged 100 days), F1
      [wild * B (Bamei)], F1 * B, F1 * Y (Yorkshire), and F1 * F1, were selected at a
      commercial pig farm. Growth performance, slaughter performance, and meat quality
      of these crossbred pigs were determined. Characteristics of fatty acids, amino
      acids, and longissimus muscle fiber in relation to growth, carcass, and meat
      quality traits were also investigated. Pigs in F1 and F1 * F1 groups had lower
      average daily weight gain, water and storage loss rates, larger meat color score,
      higher muscle amino acid levels, larger muscle fiber diameter, and higher ratio
      of flavor amino acids to unsaturated fatty acids compared to other groups.
      Crossbred pigs with higher rate of wild boar's consanguinity could improve
      production performance, slaughter performance, and meat quality. Thus,
      crossbreeding wild pig with domestic breeds might be an effective method to
      improve meat quality and flavor.

PMID- 29064064
TI  - Updated Review on the Clinical Use of Repetitive Transcranial Magnetic
      Stimulation in Psychiatric Disorders.
AB  - With the ability to modulate cortical activity, repetitive transcranial magnetic
      stimulation (rTMS) is becoming increasingly important in clinical applications
      for psychiatric disorders. Previous studies have demonstrated its promising
      efficacy in depression and schizophrenia, and emerging evidence has also been
      found in patients with anxiety disorder, obsessive-compulsive disorder, and
      substance or food craving. However, the overall literature features some
      conflicting results, varied quality of studies, and a lack of consensus on
      optimal rTMS parameters. Besides, the efficacy of rTMS in patients with
      medication-resistant symptoms has drawn most attention from clinicians. Here we
      review multi-site studies and double-blind randomized controlled trials (RCTs) in
      single sites, as well as meta-analyses of RCTs in the last three years, in order
      to update evidence on efficacy and the optimal protocol of rTMS in psychiatric
      disorders, especially for medication-resistant symptoms.

PMID- 29064067
TI  - Stem Cells in Regenerative Cardiology.
AB  - The common prevalence of heart failure and limitations in its treatment are
      leading cause of attention and interest towards the induction of cardiac
      regeneration with novel approaches. Recent studies provide growing evidence
      regarding bona fide cardiac regeneration post genetic manipulations,
      administration of stimulatory factors and myocardial injuries in animal models
      and human studies. To this end, stem cells of different sources have been tested
      to treat heart failure for the development of cellular therapies. Endogenous and
      exogenous stem cells sources used in regenerative cardiology have provided a
      proof of concept and applicability of cellular therapies in myocardial
      improvement. Recent clinical studies, especially, based on the endogenous cardiac
      progenitor and stem cells highlighted the possibility to regenerate lost
      cardiomyocytes in the myocardium. This review discusses emerging concepts in
      cardiac stem cell therapy, their sources and route of administration, and
      plausibility of de novo cardiomyocyte formation.

PMID- 29064066
TI  - Molecular Mechanism of Plant Recognition of Extracellular ATP.
AB  - Adenosine 5'-triphosphate (ATP), a ubiquitously dispersed biomolecule, is not
      only a major source of biochemical energy for living cells, but also acts as a
      critical signaling molecule through inter-cellular communication. Recent studies
      have clearly shown that extracellular ATP is involved in various physiological
      processes in plants, including root growth, stomata movement, pollen tube
      development, gravitropism, and abiotic/biotic stress responses. The first plant
      purinergic receptor for extracellular ATP, DORN1 (the founding member of the P2K
      family of purinergic receptors), was identified in Arabidopsis thaliana by a
      forward genetic screen. DORN1 consists of an extracellular lectin domain,
      transmembrane domain, and serine/threonine kinase, intracellular domain. The
      predicted structure of the DORN1 extracellular domain revealed putative key ATP
      binding residues but an apparent lack of sugar binding. In this chapter, we
      summarize recent studies on the molecular mechanism of plant recognition of
      extracellular ATP with specific reference to the role of DORN1.

PMID- 29064065
TI  - Methods for Assessing Long-Term Exposures to Outdoor Air Pollutants.
AB  - PURPOSE OF REVIEW: Epidemiological studies of health effects of long-term
      exposure to outdoor air pollution rely on different exposure assessment methods.
      This review discusses widely used methods with a special focus on new
      developments. RECENT FINDINGS: New data and study designs have been applied,
      including satellite measurements of fine particles and nitrogen dioxide (NO2).
      The methods to apply satellite data for epidemiological studies are improving
      rapidly and have already contributed significantly to national-, continental- and
      global-scale models. Spatiotemporal models have been developed allowing more
      detailed temporal resolution compared to spatial models. The development of
      hybrid models combining dispersion models, satellite observations, land use and
      surface monitoring has improved models substantially. Mobile monitoring designs
      to develop models for long-term UFP exposure have been conducted. Methods to
      assess long-term exposure to outdoor air pollution have improved significantly
      over the past decade. Application of satellite data and mobile monitoring designs
      is promising new methods.

PMID- 29064069
TI  - New genus and species of the extinct aphid family Szelegiewicziidae and their
      implications for aphid evolution.
AB  - Recently, we are witnessing an increased appreciation for the importance of the
      fossil record in phylogenetics and testing various evolutionary hypotheses.
      However, this approach brings many challenges, especially for such a complex
      group as aphids and requires a thorough morphological analysis of the extinct
      groups. The extinct aphid family Szelegiewicziidae is supposed to be one of the
      oviparous lineages in aphid evolution. New material from the rock fossil deposits
      of Shar Teg (Upper Jurassic of Mongolia), Baissa (Lower Cretaceous of Siberia
      Russia), and Burmese amber (Upper Cretaceous of Myanmar) allowed us to undertake
      a more detailed examination of the morphological features and carry out an
      analysis of the taxonomical composition and evolution of the family. This led us
      to the conclusion that evolution of the body plan and wing structure was similar
      in different, often not closely related groups, probably as a result of
      convergence. Additionally, we present a description of a new genus and two
      species (Tinaphis mongolica Zyla &Wegierek, sp. nov., and Feroorbis burmensis
      Wegierek & Huang, gen. et sp. nov.) that belong to this family.

PMID- 29064068
TI  - Dexamethasone Inhibits Copper-Induced Alpha-Synuclein Aggregation by a
      Metallothionein-Dependent Mechanism.
AB  - Intracellular aggregates of alpha-synuclein are the pathological hallmark of
      Parkinson's disease (PD) and dementia with Lewy bodies (DLB), being linked to
      neurotoxicity. Multiple triggers of alpha-synuclein aggregation have been
      implicated, including raised copper. The potential protective role of the
      endogenous copper-/zinc-binding proteins, metallothioneins (MT), has been
      explored in relation to copper-induced alpha-synuclein aggregation. Up-regulated
      endogenous expression of MT was induced in SHSY-5Y cells by the synthetic
      glucocorticoid analogue, dexamethasone. After treatment to induce endogenous MT
      expression, immunofluorescence confocal microscopy was used to quantify protein
      aggregates in cells with/without copper treatment. MT induction resulted in
      significant (p < 0.01), dose-dependent up-regulation of MT expression and
      significant reduction in Cu-dependent alpha-synuclein intracellular aggregates (p
      < 0.01) that could be suppressed by MT-specific siRNA. Ubiquitous (MT-2) and
      brain-specific (MT-3) isoforms were investigated by transient transfection of the
      GFP-fusion proteins, observing equivalent alpha-synuclein aggregate suppression
      by each. These studies indicate MT induction could have potential in PD/DLB
      neuroprotective therapy by suppressing alpha-synuclein aggregation.

PMID- 29064070
TI  - Including the 'Spiritual' Within Mental Health Care in the UK, from the
      Experiences of People with Mental Health Problems.
AB  - Spirituality as a dimension of quality of life and well-being has recently begun
      to be more valued within person-centred treatment approaches to mental health in
      the UK. The aim of this paper is to provide indicators of the extent to which
      accessing a spiritual support group may be useful within mental health recovery
      from the view point of those in receipt of it. The study design was a small-scale
      exploratory study utilising mixed methods. Quantitative methods were used to map
      the mental health, general well-being and social networks of the group. These
      were complimented by a semi-structured open-ended interview which allowed for
      Interpretative Phenomenological Analysis (IPA) of the life-history accounts of
      nine individuals with mental health problems who attended a 'spirituality support
      group'. Data from unstructured open-ended interviews with five faith chaplains
      and a mental health day centre manager were also analysed using thematic
      analysis. The views of 15 participants are therefore recounted. Participants
      reported that the group offered them: an alternative to more formal religious
      organisations, and an opportunity to settle spiritual confusions/fears. The
      'group' was also reported to generally help individual's subjective feelings of
      mental wellness through social support. Whilst the merits of spiritual care are
      appealing, convincing services to include it within treatment may still be
      difficult.

PMID- 29064071
TI  - Tuskegee as Sacred Rhetoric: Focal Point for the Emergent Field of African
      American Religion and Health.
AB  - Scholars in African American religion engage the Tuskegee Syphilis Study as the
      focal point of the African American experience in institutional medicine. Seeking
      a way forward from this history and its intentional evil, the author proposes to
      position Tuskegee as a form of Lynch's culturally contextual sacred rhetoric to
      make use of its metaphoric value in the emerging field of African American
      religion and health. In this broader meaning-making frame, Tuskegee serves as a
      reminder that African American religious sensibility has long been an agential
      resource that counters abuse of the Black body. It also acknowledges the complex
      decisions facing African American clinical trial participants.

PMID- 29064072
TI  - Physicians' professional performance: an occupational health psychology
      perspective.
AB  - INTRODUCTION: Physician work engagement is considered to benefit physicians'
      professional performance in clinical teaching practice. Following an occupational
      health psychology perspective, this PhD report presents research on how
      physicians' professional performance in both doctor and teacher roles can be
      facilitated by work engagement and how work engagement is facilitated by job
      resources and personality traits. METHODS: First, we conducted a systematic
      review on the impact of physician work engagement and related constructs (e. g.
      job satisfaction) on physicians' performance in patient care. We additionally
      investigated physician work engagement and job resources in relation to patient
      care experience with physicians' performance at ten outpatient clinics covering
      two hospitals. In a following multicentre survey involving 61 residency training
      programs of 18 hospitals, we studied associations between physician work
      engagement and personality traits with resident evaluations of physicians'
      teaching performance. RESULTS: The findings showed that physician work engagement
      was associated with fewer reported medical errors and that job satisfaction was
      associated with better communication and patient satisfaction. Autonomy and
      learning opportunities were positively associated with physician work engagement.
      Work engagement was positively associated with teaching performance. In addition,
      physician work engagement was most likely supported by personality trait
      conscientiousness (e. g. responsibility). CONCLUSION: Given the reported
      associations of physician work engagement with aspects of their professional
      performance, hospitals could support physician work engagement in service of
      optimal performance in residency training and patient care. This could be
      facilitated by worker health surveillance, peer support or promoting job crafting
      at the individual or team level.

PMID- 29064074
TI  - Diversity in alphabeta and betaalpha Loop Connections in TIM Barrel Proteins:
      Implications for Stability and Design of the Fold.
AB  - The (betaalpha)8/TIM barrel is one of the most common folds of known protein
      structures facilitating diverse catalytic functions. The fold is formed by the
      repetition of the basic betaalphabeta building block in which the beta-strands
      are followed by alpha-helices eight times alternating in sequence and structure.
      alphabeta and betaalpha loops connecting alpha-helices to the beta-strands and
      the beta-strands to the alpha-helices contribute to stability and function,
      respectively, an inherent imposition by the TIM barrel architecture itself. In
      this study, alphabeta and betaalpha loops from a data set of 430 non-redundant,
      high-resolution triosephosphate isomerase (TIM) barrels bearing sequence homology
      of <30% were analyzed for their amino acid propensities, sequence profiles, and
      positional preferences of amino acids. While the distribution of short
      connections is significantly higher in alphabeta loops, there appears to be no
      such preference in betaalpha loops. Glycine, proline, lysine, and arginine tend
      to show greater preference to occur in alphabeta loops, whereas serine,
      threonine, cysteine, tryptophan, and histidine occur more frequently in betaalpha
      loops. In addition, striking dissimilarities in sequence and positional
      preferences of amino acids, especially, in short, alphabeta and betaalpha loops
      are observed. Together, the analysis suggests the role for short loops and
      charged residues in promoting both non-polar and polar interactions and in beta
      strand registry. The observed diversity, perhaps, dictates the distinct role of
      alphabeta and betaalpha loops in stability and function, respectively. In
      summary, the overall observations and reasoning, in addition to steering protein
      engineering efforts on TIM barrel design and stabilization can provide the basis
      for incorporating consensus loop sequences for designing independently folding
      betaalphabeta modules.

PMID- 29064073
TI  - Genuine participation in participant-centred research initiatives: the rhetoric
      and the potential reality.
AB  - The introduction of Web 2.0 technology, along with a population increasingly
      proficient in Information and Communications Technology (ICT), coupled with the
      rapid advancements in genetic testing methods, has seen an increase in the
      presence of participant-centred research initiatives. Such initiatives, aided by
      the centrality of ICT interconnections, and the ethos they propound seem to
      further embody the ideal of increasing the participatory nature of research,
      beyond what might be possible in non-ICT contexts alone. However, the majority of
      such research seems to actualise a much narrower definition of 'participation'
      where it is merely the case that such research initiatives have increased contact
      with participants through ICT but are otherwise non-participatory in any
      important normative sense. Furthermore, the rhetoric of participant-centred
      initiatives tends to inflate this minimalist form of participation into something
      that it is not, i.e. something genuinely participatory, with greater connections
      with both the ICT-facilitated political contexts and the largely non-ICT
      participatory initiatives that have expanded in contemporary health and research
      contexts. In this paper, we highlight that genuine (ICT-based) 'participation'
      should enable a reasonable minimum threshold of participatory engagement through,
      at least, three central participatory elements: educative, sense of being
      involved and degree of control. While we agree with criticisms that, at present,
      genuine participation seems more rhetoric than reality, we believe that there is
      clear potential for a greater ICT-facilitated participatory engagement on all
      three participatory elements. We outline some practical steps such initiatives
      could take to further develop these elements and thereby their level of ICT
      facilitated participatory engagement.

PMID- 29064075
TI  - O blood type is a risk factor for upper gastrointestinal bleeding.

PMID- 29064076
TI  - CHA2DS2-VASc score predicts short- and long-term outcomes in patients with acute
      ischemic stroke treated with intravenous thrombolysis.
AB  - The CHA2DS2-VASc score is a validated tool to assess the thromboembolic risk in
      patients with atrial fibrillation. Pre-stroke CHA2DS2-VASc score may predict
      outcome in patients with acute ischemic stroke (AIS) without atrial fibrillation.
      The aim of this study was to investigate if the pre-stroke CHA2DS2-VASc score is
      able to predict short- and long-term outcomes in AIS patients treated with
      intravenous thrombolysis (IVT). The study group consisted of 256 consecutive
      patients admitted to the Udine University Hospital with AIS and underwent IVT
      between January 2015 to March 2017. The pre-stroke CHA2DS2-VASc score for each
      patient was calculated from the collected baseline data. Patients were classified
      into three groups according to their pre-stroke CHA2DS2-VASc score: a score of 0
      of 1, a score of 2 or 3 and a score above 3. Primary outcome measures were: rate
      of favorable outcome at 90-days and at 1-year, and mortality at 90-days and at 1
      year. Data on functional outcome and mortality 1 year after stroke were collected
      in 165 patients (65% of the entire sample). Favorable outcome was defined as a
      modified Rankin Scale score <= 2. Compared with the CHA2DS2-VASc score 0-1 group,
      patients with higher CHA2DS2-VASc scores had a worse outcome and a higher
      mortality 3 months and 1 year after stroke. The diagnostic performance of the
      CHA2DS2-VASc score as judged with AUC-ROC was 0.70 (95% CI, 0.64-0.76; p < 0.001)
      for favorable outcome at 90-days, 0.78 (95% CI, 0.71-0.85; p < 0.001) for
      favorable outcome at 1-year, 0.71 (95% CI 0.61-0.79) for mortality at 90-days,
      0.73 (95% CI 0.64-0.80; p < 0.001) for mortality at 1-year. Pre-stroke CHA2DS2
      VASc score represents a good predictor for short- and long-term outcomes in AIS
      patients treated with IVT.

PMID- 29064077
TI  - HSP27 immunization reinforces AII amacrine cell and synapse damage induced by
      S100 in an autoimmune glaucoma model.
AB  - Previous studies have revealed a loss of retinal ganglion cells (RGCs) and optic
      nerve fibers after immunization with the S100B protein. Addition of heat shock
      protein 27 (HSP27) also leads to a decrease of RGCs. Our present aim has been to
      analyze various retinal cell types after immunization with S100B or S100B + HSP27
      (S100 + HSP). After 28 days, retinas were processed for immunohistology and
      Western blot. RGCs, immunostained for NeuN, were significantly decreased in the
      S100 and the S100 + HSP groups. Significantly fewer ChAT+ cells were noted in
      both groups, whereas parvalbumin+ cells were only affected in the S100 + HSP
      group. Western blot results also revealed fewer ChAT signals in both immunized
      groups. No changes were noted with regard to PKCalpha+ rod bipolar cells, whereas
      a significant loss of recoverin+ cone bipolar cells was observed in both groups
      via immunohistology and Western blot. The presynaptic marker Bassoon and the
      postsynaptic marker PSD95 were significantly reduced in the S100 + HSP group.
      Opsin+ and rhodopsin+ photoreceptors revealed no changes in either group. Thus,
      the inner retinal layers are affected by immunization. However, the combination
      of S100 and HSP27 has a stronger additive effect on the retinal synapses and AII
      amacrine cells.

PMID- 29064078
TI  - Defective Wnt3 expression by testicular Sertoli cells compromise male fertility.
AB  - Testicular Sertoli cells make a niche for the division and differentiation of
      germ cells. Sertoli cells respond to increased follicle-stimulating hormone (FSH)
      and testosterone (T) levels at the onset of puberty by producing paracrine
      factors which affect germ cells and trigger robust onset of spermatogenesis. Such
      paracrine support to germ cells is absent during infancy, despite Sertoli cells
      being exposed to high FSH and T within the infant testis. This situation is
      similar to certain cases of male idiopathic infertility where post-pubertal
      Sertoli cells fail to support germ cell division and differentiation in spite of
      endogenous or exogenous hormonal support. Defective Sertoli cells in such
      individuals may fail to express the full complement of their paracrine
      repertoire. Identification and supplementation with such factors may overcome
      Sertoli cells deficiencies and help trigger quantitatively and qualitatively
      normal differentiation of germ cells. To this end, we compared the transcriptome
      of FSH- and T-treated infant and pubertal monkey Sertoli cells by DNA microarray.
      Expression of Wnt3, a morphogen of the Wnt/beta-catenin pathway, was higher in
      pubertal Sertoli cells relative to infant Sertoli cells. Transgenic mice were
      generated by us in which Wnt3 expression was curtailed specifically in post
      pubertal Sertoli cells by shRNA. Subfertility and oligozoospermia were noticed in
      such animals with low Wnt3 expression in post-pubertal Sertoli cells along with
      diminished expression of Connexin43, a gap-junctional molecule essential for germ
      cell development. We report that the FSH- and T-targetedf Wnt3 governs Sertoli
      cell-mediated regulation of spermatogenesis and hence is crucial for fertility.

PMID- 29064080
TI  - Photoprotection in intact cells of photosynthetic bacteria: quenching of
      bacteriochlorophyll fluorescence by carotenoid triplets.
AB  - Upon high light excitation in photosynthetic bacteria, various triplet states of
      pigments can accumulate leading to harmful effects. Here, the generation and
      lifetime of flash-induced carotenoid triplets (3Car) have been studied by
      observation of the quenching of bacteriochlorophyll (BChl) fluorescence in
      different strains of photosynthetic bacteria including Rvx. gelatinosus
      (anaerobic and semianaerobic), Rsp. rubrum, Thio. roseopersicina, Rba.
      sphaeroides 2.4.1 and carotenoid- and cytochrome-deficient mutants Rba.
      sphaeroides Ga, R-26, and cycA, respectively. The following results were
      obtained: (1) 3Car quenching is observed during and not exclusively after the
      photochemical rise of the fluorescence yield of BChl indicating that the charge
      separation in the reaction center (RC) and the carotenoid triplet formation are
      not consecutive but parallel processes. (2) The photoprotective function of 3Car
      is not limited to the RC only and can be described by a model in which the
      carotenoids are distributed in the lake of the BChl pigments. (3) The observed
      lifetime of 3Car in intact cells is the weighted average of the lifetimes of the
      carotenoids with various numbers of conjugated double bonds in the bacterial
      strain. (4) The lifetime of 3Car measured in the light is significantly shorter
      (1-2 MUs) than that measured in the dark (2-10 MUs). The difference reveals the
      importance of the dynamics of 3Car before relaxation. The results will be
      discussed not only in terms of energy levels of the 3Car but also in terms of the
      kinetics of transitions among different sublevels in the excited triplet state of
      the carotenoid.

PMID- 29064079
TI  - Molecular mechanisms of alpha-synuclein and GBA1 in Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative movement disorder characterized
      pathologically by the presence of Lewy bodies comprised of insoluble alpha
      (alpha)-synuclein. Pathological, clinical and genetic studies demonstrate that
      mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase
      (GCase) that is deficient in Gaucher's disease, are important risk factors for
      the development of PD. The molecular mechanism for the association between these
      two diseases is not completely understood. We discuss several possible mechanisms
      that may lead to GBA1-related neuronal death and alpha-synuclein accumulation
      including disruptions in lipid metabolism, protein trafficking and impaired
      protein quality control mechanisms. Elucidating the mechanism between GCase and
      alpha-synuclein may provide insight into potential therapeutic pathways for PD
      and related synucleinopathies.

PMID- 29064081
TI  - Recommendations for the treatment of hepatitis C virus infection in chronic
      kidney disease: a position statement by the Spanish association of the liver and
      the kidney.
AB  - Hepatitis C virus (HCV) infection is one of the main causes of liver cirrhosis
      worldwide. The long-term impact of HCV infection is highly variable, ranging from
      minimal histological changes to extensive fibrosis with hepatocellular carcinoma.
      The development of HCV drugs has increased dramatically in recent years, even in
      special populations such as chronic kidney disease patients. Classical treatment
      of chronic hepatitis C was based on the administration of interferon and
      ribavirin for 24-48 weeks, which was associated with a poor viral response and a
      high rate of side effects, especially in patients with a lower estimated
      glomerular filtration rate. The current high availability of the new direct
      acting antivirals renders the classification of these agents for this special
      population necessary. The Spanish Association of the Liver and the Kidney has
      produced a position statement on the treatment of HCV infection in chronic kidney
      disease patients since the evidence to guide this treatment is scant and what
      evidence does exist is weak. The recommendations are based on the results of
      clinical trials and controlled studies conducted to date, with data published
      hitherto by the authors of these studies. Since the indications for treatment
      have been evaluated by other societies or are dependent on internal clinical
      protocols, the main goal of this position statement is to assist in decision
      making when choosing a therapeutic option.

PMID- 29064082
TI  - Abnormal 1-hour post-load glycemia during pregnancy impairs post-partum metabolic
      status: a single-center experience.
AB  - PURPOSE: Recent evidence indicates that people with normal glucose tolerance
      (NGT) but 1-h post-load plasma glucose (1-h OGTT) >= 155 mg/dl have an increased
      risk for developing Type 2 diabetes mellitus (T2DM), determining a new risk
      category with deeper metabolic impairment. The aim of this study was to identify,
      among women with gestational diabetes (GDM), which alterations at OGTT during
      pregnancy are more frequently associated with 1-h OGTT >= 155 mg/dl at post
      partum examination. METHODS: Among 297 women affected by GDM, we retrospectively
      evaluated 244 resulted NGT after delivery. Based on post-partum glucose levels at
      1-h OGTT, these people were divided into 188 cases (77.0%) with 1-h OGTT < 155
      mg/dl (L-NGT) and 56 (23.0%) with 1-h OGTT >= 155 mg/dl (H-NGT). RESULTS:
      Abnormal glucose levels at 1-h OGTT during pregnancy (>= 180 mg/dl) were more
      frequent in H-NGT than in L-NGT (39.3 vs. 24.6%, odds ratio 3.7 [95% CI 1.4-9.6];
      p = 0.016). Moreover, H-NGT showed more frequently the simultaneous alteration of
      all three OGTT plasma glucose values during pregnancy (10.7 vs. 2.1%, odds ratio
      4.5 [95% CI 1.5-20.3]; p = 0.038) and less frequently the alteration of fasting
      plasma glucose alone (14.3 vs. 30.8%, odds ratio 0.4 [95% CI 0.1-0.7]; p =
      0.028). CONCLUSIONS: Abnormal 1-h OGTT during pregnancy predicts an increased
      risk for post-partum 1-h OGTT >= 155 mg/dl in women with previous GDM. Even if
      NGT after delivery, these women may require a closer long-term post-partum follow
      up, being at higher risk to develop future glucose intolerance.

PMID- 29064083
TI  - New insights into flavivirus biology: the influence of pH over interactions
      between prM and E proteins.
AB  - Diseases caused by flaviviruses, such as dengue and zika, are globally recognized
      as major threats. During infection, a critical point in their replicative cycle
      is the maturation step, which occurs throughout the cellular exocytic pathway.
      This step is a pH-dependent process that involves the modification of the viral
      envelope by converting prM (pre-membrane) into M (membrane) proteins with the
      release of a "pr peptide". After this reaction, the pr peptides remain bound to
      the viral envelope while the virions cross the acidic trans-Golgi network, and
      are released only at neutral pH after secretion of the virus particles. Despite
      this current knowledge, the molecular basis of the flavivirus maturation step is
      largely unknown. Here, based on the crystal structure of the dengue pr-E complex
      ("pr peptide" bound to virus envelope protein) and using molecular dynamics
      simulations, we found that the pH shift from acidic to neutral yields
      considerable structural changes in the system. Dynamic cross correlation maps and
      root mean square deviation analyses revealed that the pr-E junction is clearly
      unstable under neutral pH. Secondary structure analysis also revealed that the
      fusion loop region, present in the E protein, is sensitive to pH and tends to
      unstructure at a neutral environment. Moreover, we found that five residues
      present in the E protein, Gly102, His244, Thr70, Thr68 and Asn67 are critical to
      confer stability to the pr-E complex while inside the Golgi apparatus. This work
      brings details about the dynamical behavior of the pr-E system, helps to better
      understand the flavivirus biology and may also be of use in the development of
      novel antiviral strategies.

PMID- 29064084
TI  - Adverse cardiac events in out-patients initiating clozapine treatment: a
      nationwide register-based study.
AB  - OBJECTIVE: Using national Danish registers, we estimated rates of clozapine
      associated cardiac adverse events. Rates of undiagnosed myocarditis were
      estimated by exploring causes of death after clozapine initiation. METHOD:
      Through nationwide health registers, we identified all out-patients initiating
      antipsychotic treatment (January 1, 1996-January 1, 2015). Rates of clozapine
      associated myocarditis and pericarditis within 2 months from clozapine initiation
      and rates of cardiomyopathy within 1-2 years from clozapine initiation were
      compared to rates for other antipsychotics. Mortality within 2 months from
      clozapine initiation was extracted. RESULTS: Three thousand two hundred and sixty
      two patients of a total 7932 patients initiated clozapine as out-patients
      (41.12%). One patient (0.03%) developed myocarditis, and no patients developed
      pericarditis within 2 months from clozapine initiation. Two (0.06%) and four
      patients (0.12%) developed cardiomyopathy within 1 and 2 years respectively.
      Rates were similar for other antipsychotics. Twenty-six patients died within 2
      months from clozapine initiation. Pneumonia (23.08%) and stroke (11.54%) were the
      main causes of death. We estimated the maximum rate of clozapine-associated fatal
      myocarditis to 0.28%. CONCLUSION: Cardiac adverse effects in Danish out-patients
      initiating clozapine treatment are extremely rare and these rates appear to be
      comparable to those observed for other antipsychotic drugs.

PMID- 29064086
TI  - Histopathological and ultrastructural assessment of two mugilid species infected
      with myxozoans and helminths.
AB  - The histopathology and ultrastructure of the intestine of mullets, Liza ramada
      and Liza saliens, from Comacchio lagoons (northern Italy) naturally infected with
      myxozoans and helminths were investigated and described. Sixty-two (80.5%) of 77
      mullets harboured one or more of the following parasites species: Myxobolus
      mugchelo (Myxozoa), Neoechinorhynchus agilis (Acanthocephala), Haplosplanchnus
      pachysomus and Dicrogaster contractus (Digenea). Co-occurrence of helminths with
      myxozoans was common. The main damage caused by digeneans was destruction of the
      mucosal epithelium of the villi, necrosis and degeneration of intestinal
      epithelial cells. More severe intestinal damage was caused by acanthocephalans
      which reach the submucosa layer with their proboscis. At the site of helminths
      infection, several mast cells (MCs), rodlet cells (RCs), mucous cells and few
      neutrophils and macrophages were observed in the epithelium. RCs and mucous cells
      exhibited discharge activity in close vicinity to the worm's tegument. M.
      mugchelo conspicuous plasmodia were encysted mainly in muscle and submucosa
      layers of the intestine. Indeed, spores of M. mugchelo were documented within the
      epithelial cells of host intestine and in proximity to MCs. Degranulation of the
      MCs near the myxozoans was very frequent.

PMID- 29064087
TI  - Sentinel lymph node biopsy status is not the most powerful predictor of prognosis
      in cutaneous melanoma.
AB  - Sentinel lymph node (SLN) status has been advocated in several recently published
      articles as the single most valuable prognostic marker for melanoma, and of
      greater prognostic importance than more established parameters such as Breslow
      thickness. A careful examination of the evidence for these claims, however,
      indicates that they are not substantiated by the available data, are somewhat
      misleading and suggest misinterpretation of the statistical analysis of the
      papers to which they refer. We will examine the basis for these claims and show
      why they are invalid.

PMID- 29064088
TI  - Systemic sclerosis impacts right heart and cardiac autonomic nervous system.
AB  - AIM: To evaluate the influence of systemic sclerosis (SSc) on right ventricular
      (RV) remodeling by two- and three-dimensional echocardiography (2DE and 3DE) and
      heart rate variability (HRV). METHODS: Forty-five SSc patients and 35 age- and
      gender-matched healthy controls underwent clinical examination, 24-h Holter
      monitoring, and comprehensive 2DE and 3DE. RESULTS: 2DE RV global and RV free
      wall longitudinal strains, as well as 2DE RV endocardial, mid-myocardial, and
      epicardial longitudinal strains were lower in SSc subjects, who exhibited greater
      3DE RV volumes but lower 3DE RV ejection fraction than controls. HRV indices were
      impaired in SSc subjects. These differences in RV global and free wall
      longitudinal strain, layer-specific strains, and ejection fraction, were
      associated with HRV indices independently of demographic, clinical, and
      echocardiographic parameters. Modified Rodnan Skin Score, clinical indicator of
      skin involvement in SSc, was associated with HRV parameters, RV layer-specific
      mechanics, and RV ejection fraction. CONCLUSION: SSc affects RV function and
      mechanics of all myocardial layers, as well as cardiac autonomic nervous
      function. HRV indices are significantly associated with RV function, RV
      deformation, and skin involvement in SSc patients.

PMID- 29064089
TI  - High-risk squamous cell carcinoma masquerading as dense inflammation on Mohs
      frozen sections.
AB  - High-risk squamous cell carcinoma (SCC) can present a unique challenge in Mohs
      surgery. This case report describes how high-risk SCC may masquerade as only a
      dense inflammation on frozen sections. This feature should raise the index of
      suspicion for hidden SCC and be a routine indication for further processing by
      paraffin sections and immunohistochemistry.

PMID- 29064085
TI  - The biology of natural killer cells during sepsis.
AB  - Natural killer (NK) cells are large granular lymphocytes largely recognized for
      their importance in tumour surveillance and the host response to viral
      infections. However, as the major innate lymphocyte population, NK cells also
      coordinate early responses to bacterial infections by amplifying the
      antimicrobial functions of myeloid cells, especially macrophages, by production
      of interferon-gamma (IFN-gamma). Alternatively, excessive NK cell activation and
      IFN-gamma production can amplify the systemic inflammatory response during sepsis
      resulting in increased physiological dysfunction and organ injury. Our
      understanding of NK cell biology during bacterial infections and sepsis is mostly
      derived from studies performed in mice. Human studies have demonstrated a
      correlation between altered NK cell functions and outcomes during sepsis.
      However, mechanistic understanding of NK cell function during human sepsis is
      limited. In this review, we will review the current understanding of NK cell
      biology during sepsis and discuss the challenges associated with modulating NK
      cell function during sepsis for therapeutic benefit.

PMID- 29064090
TI  - Different communication strategies for disclosing a diagnosis of schizophrenia
      and related disorders.
AB  - BACKGROUND: Delivering the diagnosis of a serious illness is an important skill
      in most fields of medicine, including mental health. Research has found that
      communication skills can impact on a person's recall and understanding of the
      diagnosis, treatment options and prognosis. People may feel confused and
      perplexed when information about their illness is not communicated properly.
      Sharing information about diagnosis of a serious mental illness is particularly
      challenging. The nature of mental illness is often difficult to explain since
      there may be no clear aetiology, and the treatment options and prognosis may vary
      enormously. In addition, newly diagnosed psychiatric patients, who are actively
      ill, often may not accept their diagnosis due to lack of insight or stigma
      attached to the condition. There are several interventions that aim to help
      clinicians to communicate life changing medical diagnoses to people; however,
      little is known specifically for delivering a diagnosis of schizophrenia.
      OBJECTIVES: To evaluate evidence from randomised controlled trials (RCTs) for the
      efficacy of different communication strategies used by clinicians to inform
      people about the diagnosis and outcome of schizophrenia compared with treatment
      as usual and to compare efficacy between different communication strategies.
      SEARCH METHODS: On 22 June 2015 and 29 June 2016, we searched the Cochrane
      Schizophrenia Group's Study-Based Register of Trials. We also searched sources of
      grey literature (e.g., dissertations, theses, clinical reports, evaluations
      published on websites, clinical guidelines and reports from regulatory agencies).
      SELECTION CRITERIA: We planned to include all relevant RCTs that included adults
      with schizophrenia or related disorders, including schizophreniform disorder,
      schizoaffective disorder and delusional disorder. The trials would have
      investigated the effects of communication strategy or strategies that helped
      clinicians deliver information specifically about a diagnosis of schizophrenia
      (which can also include communication regarding the treatment options available
      and prognosis). DATA COLLECTION AND ANALYSIS: Review authors independently
      examined all reports from the searches for any relevant studies. We planned to
      extract data independently. For binary outcomes, we would have calculated risk
      ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis.
      For continuous data, we would have estimated the mean difference (MD) between
      groups and its 95% CI. We would have employed a random-effects model for
      analyses. We planned to assess risk of bias for included studies. We created a
      'Summary of findings' table using GRADE. MAIN RESULTS: The searches identified 44
      records which appeared to be relevant to the aims of the review. We obtained full
      reports for seven potential studies; however, after close inspection none of
      these studies met the inclusion criteria. AUTHORS' CONCLUSIONS: Good
      communication of diagnosis can affect treatment planning, compliance and patient
      outcomes, especially in the case of conditions such as schizophrenia, which has
      the potential to cause serious life disruption for both people with schizophrenia
      and their carers. Currently, there is no evidence based on findings from RCTs
      assessing the effects of communication strategies for disclosing the diagnosis of
      schizophrenia and related disorders. Research is required.

PMID- 29064091
TI  - DNA vaccines for fish: Review and perspectives on correlates of protection.
AB  - Recently in 2016, the European Medicines Agency (EMA) recommended granting a
      marketing authorization in the EU for "Clynav," a DNA vaccine against salmon
      pancreas disease (salmonid alphavirus-3). Generally, DNA vaccines induce both
      early and late immune responses in fish that may be protective against disease.
      Several transcriptomic approaches have been performed to map immunome profiles
      following DNA vaccination, but the precise immune mechanism(s) that is
      responsible for protection is not known, although reasonable suggestions have
      been made. The current review includes an overview on main transcriptomic
      findings from microarray experiments after DNA vaccination against VHSV, IHNV,
      HIRRV and IPNV-with considerations of what can be considered as correlates of
      protection (CoP) or merely a surrogate of protection. Identification and use of
      correlates of protection (COPs) may be a strategic tool for accelerated and
      targeted vaccine design, testing and licensure. General rules on what can be
      considered as CoPs can be extracted from past knowledge on protective immune
      responses following vaccination that induced protection. Lastly, there will be an
      overview on non-viral molecular adjuvants that have been exploited to obtain
      higher vaccine potencies and efficacies.

PMID- 29064092
TI  - Effects of vitamin D deficiency on left atrial function as evaluated by 2D
      speckle-tracking echocardiography.
AB  - PURPOSE: Vitamin D deficiency is prevalent the world over, and some of its
      effects on the cardiovascular system have been previously demonstrated. We
      evaluated left atrial (LA) function via 2D speckle-tracking echocardiography
      (2DSTE) in subjects with and without vitamin D deficiency. METHODS: Ninety-seven
      consecutive patients without significant coronary artery disease on selective
      coronary angiography were incorporated in our study and divided according to
      their serum level of vitamin D into 2 groups: with and without vitamin D
      deficiency. RESULTS: The early diastolic strain rate, as a marker of LA conduit
      function, was increased in patients with vitamin D deficiency (P = .008) and
      after adjustment for age (P = .046). However, after adjustment for all the
      confounding factors, vitamin D deficiency showed only a trend to be the
      independent determinant of LA early diastolic longitudinal strain rate (SRE, P =
      .065). CONCLUSIONS: Our findings indicated that LA function, as evaluated by
      2DSTE, was not different between subjects with and without vitamin D deficiency
      after adjustment for the confounding factors.

PMID- 29064093
TI  - Focal cortical malformations in children with early infantile epilepsy and PCDH19
      mutations: case report.
AB  - : In this case report we assess the occurrence of cortical malformations in
      children with early infantile epilepsy associated with variants of the gene
      protocadherin 19 (PCDH19). We describe the clinical course, and electrographic,
      imaging, genetic, and neuropathological features in a cohort of female children
      with pharmacoresistant epilepsy. All five children (mean age 10y) had an early
      onset of epilepsy during infancy and a predominance of fever sensitive seizures
      occurring in clusters. Cognitive impairment was noted in four out of five
      patients. Radiological evidence of cortical malformations was present in all
      cases and, in two patients, validated by histology. Sanger sequencing and
      Multiplex Ligation-dependent Probe Amplification analysis of PCDH19 revealed
      pathogenic variants in four patients. In one patient, array comparative genomic
      hybridization showed a microdeletion encompassing PCDH19. We propose molecular
      testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with
      onset in early infancy, seizures in clusters, and fever sensitivity. Structural
      lesions are to be searched in patients with PCDH19 pathogenic variants. Further,
      PCDH19 analysis should be considered in epilepsy surgery evaluation even in the
      presence of cerebral structural lesions. WHAT THIS PAPER ADDS: Focal cortical
      malformations and monogenic epilepsy syndromes may coexist. Structural lesions
      are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic
      variants with refractory focal seizures.

PMID- 29064094
TI  - Cardiac amyloidosis is associated with increased aortic stiffness.
AB  - OBJECTIVE: Cardiac amyloidosis (CA) is as an infiltrative disorder primarily
      caused by extracellular tissue deposition of amyloid fibrils in the myocardial
      interstitium. The current study was designed to test whether alterations in
      ascending aortic elastic properties could be detected by echocardiography in CA
      patients, and to compare their results to controls. PATIENTS AND METHODS: We
      included 19 CA patients from which CA proved to be AL amyloidosis in 17 cases and
      transthyretin (TTR) amyloidosis in 2 cases. Their results were compared to 20 age
      , gender-, and risk factor-matched controls. RESULTS: There was significantly
      greater interventricular septum and left ventricular (LV) posterior wall
      thickness, lower LV ejection fraction and greater E/A in CA patients than in
      controls, suggesting systolic, and diastolic dysfunction. CA patients also showed
      significantly reduced aortic strain and pulsatile change in aortic diameter, and
      increased aortic stiffness index. CONCLUSION: These results suggest increased
      aortic stiffness in CA patients.

PMID- 29064095
TI  - Prenatal sonographic diagnosis of cephalopagus conjoined twins at 14 weeks of
      pregnancy.
AB  - Conjoined twins are extremely rare and are a type of monozygotic twins that occur
      due to an incomplete embryonic division on postconception day 13 to 15. Eight
      different types of conjoined twins have been described in the literature.
      Management of the condition depends on the site and extent of the union. We
      present a case of cephalopagus twins diagnosed at 14 weeks of gestation.

PMID- 29064096
TI  - Chemical peels: A review of current practice.
AB  - Chemical peels belong to a group of cutaneous resurfacing procedures that are
      used in the treatment of photoageing, inflammatory dermatoses, epidermal
      proliferations, pigmentary disorders and scarring. This review describes best
      current practice, highlights recent advances in chemical peel technology and
      discusses the recommended uses for different peel types. It also presents the
      results of a survey of the chemical peeling practices of 30 Australian
      dermatologists.

PMID- 29064097
TI  - Transcranial direct current stimulation for rehabilitating the brain.

PMID- 29064098
TI  - Latin-American Academy of Child Development and Disabilities: the first steps
      into the future.

PMID- 29064099
TI  - Congenital anomalies and cerebral palsy: cause or comorbidity?

PMID- 29064100
TI  - Gait performance measures for children with neuromotor disorders in inpatient
      rehabilitation.

PMID- 29064101
TI  - Reflections on the usefulness of the term 'health-related quality of life'.

PMID- 29064102
TI  - A rapid method for simultaneously diagnosing four shrimp diseases using PCR-DNA
      chromatography method.

PMID- 29064103
TI  - Establishment and characterization of a new cell line from koi brain (Cyprinus
      carpio L.).
AB  - A novel permanently growing brain cell line from koi (Cyprinus carpio L.) (KB
      cell line) was established, and its suitability for detection of koi herpesvirus
      (KHV) was demonstrated in this study. The KB cell line was optimally maintained
      at 27 degrees C in Leibovitz's L-15 medium supplemented with 10% foetal bovine
      serum (FBS). It was subcultured more than 100 times, and chromosome analysis
      revealed that 51.54% of KB cells at passage 80 maintained the abnormal diploid
      chromosome number 2n = 96 while the modal chromosome number was 2n = 100. The
      cell line was cryopreserved in liquid nitrogen at -196 degrees C and was
      recovered from storage after 1 year with good cell viability and vitality. The
      results of virus isolation demonstrated that KB cells were susceptible to KHV,
      which was shown by the presence of an obvious cytopathic effect and abundant
      virus particles. The viral titres of KHV in KB reached 105.73 TCID50 /0.1 ml
      within 7 days. Immunofluorescence and Western blot assays confirmed that KB
      replicated KHV. The newly established KB cell line will serve as a useful tool to
      elucidate KHV disease (KHVD) pathogenesis.

PMID- 29064104
TI  - Antimicrobial susceptibility of Flavobacterium psychrophilum isolates from the
      United Kingdom.
AB  - Routine application of antimicrobials is the current treatment of choice for
      rainbow trout fry syndrome (RTFS) or bacterial coldwater disease (BCWD) caused by
      Flavobacterium psychrophilum. In this study, the antimicrobial susceptibilities
      of 133 F. psychrophilum isolates, 118 of which were from the UK, were evaluated
      by broth microdilution and disc diffusion methods following VET04-A2 and VET03-A
      guidelines of Clinical and Laboratory Standards Institute (CLSI), respectively.
      Isolates were categorized as wild type (fully susceptible, WT) or non-wild type
      (NWT) using normalized resistance interpretation (NRI)-determined cut-off values
      (COWT ). Broth microdilution testing showed that only 12% of UK isolates were WT
      to oxolinic acid (MIC COWT  <= 0.25 mg/L) and 42% were WT for oxytetracycline
      (MIC COWT  <= 0.25 mg/L). In contrast, all the isolates tested were WT (MIC COWT 
      <= 2 mg/L) for florfenicol, the main antimicrobial for RTFS control in the UK.
      Disc diffusion-based COWT values were >=51 mm for 10 MUg amoxicillin, >=44 mm for
      30 MUg florfenicol, >=30 mm for 2 MUg oxolinic acid and >=51 mm for 30 MUg
      oxytetracycline. There was a high categorical agreement between the
      classifications of the isolates by two testing methods for florfenicol (100%),
      oxytetracycline (93%) and oxolinic acid (99%).

PMID- 29064105
TI  - Carp edema virus from three genogroups is present in common carp in Hungary.
AB  - Hungary is an important carp producer with intensive trading relationships with
      farms in other carp-producing areas in Europe. Carp in Europe were recently found
      infected with carp edema virus (CEV), a poxvirus which causes the koi sleepy
      disease (KSD) syndrome. Moribund carp were collected from 17 fish farms and
      angling ponds in different regions of Hungary. Histological analysis of gills
      from these carp revealed a proliferation of the interlamellar epithelium and an
      infiltration by eosinophilic cells. In 13 of 17 of these carp, CEV DNA was
      detected by qPCR and in seven fish more than 1 * 104 copies of virus-specific DNA
      sequences per 250 ng of DNA, which could be considered as clinically relevant and
      a cause of disease. A phylogenetic analysis of the sequences revealed that all
      three genogroups of CEV were present in Hungarian common carp with genogroup I
      being most abundant. These results support the hypothesis of a prolonged presence
      of CEV in European carp populations and suggest that previous outbreaks of KSD
      were not recorded or misdiagnosed. Hence, a testing of carp and koi for infection
      with CEV should be included into disease surveillance programmes to prevent
      further spreading of this disease.

PMID- 29064108
TI  - Strategies to diversify natural products for drug discovery.
AB  - Natural product libraries contain specialized metabolites derived from plants,
      animals, and microorganisms that play a pivotal role in drug discovery due to
      their immense structural diversity and wide variety of biological activities. The
      strategies to greatly extend natural product scaffolds through available
      biological and chemical approaches offer unique opportunities to access a new
      series of natural product analogues, enabling the construction of diverse natural
      product-like libraries. The affordability of these structurally diverse molecules
      has been a crucial step in accelerating drug discovery. This review provides an
      overview of various approaches to exploit the diversity of compounds for natural
      product-based drug development, drawing upon a series of examples to illustrate
      each strategy.

PMID- 29064106
TI  - Integration of mechanistic and pharmacokinetic information to derive oral
      reference dose and margin-of-exposure values for hexavalent chromium.
AB  - The current US Environmental Protection Agency (EPA) reference dose (RfD) for
      oral exposure to chromium, 0.003 mg kg-1  day-1 , is based on a no-observable
      adverse-effect-level from a 1958 bioassay of rats exposed to <=25 ppm hexavalent
      chromium [Cr(VI)] in drinking water. EPA characterizes the confidence in this RfD
      as "low." A more recent cancer bioassay indicates that Cr(VI) in drinking water
      is carcinogenic to mice at >=30 ppm. To assess whether the existing RfD is health
      protective, neoplastic and non-neoplastic lesions from the 2 year cancer bioassay
      were modeled in a three-step process. First, a rodent physiological-based
      pharmacokinetic (PBPK) model was used to estimate internal dose metrics relevant
      to each lesion. Second, benchmark dose modeling was conducted on each lesion
      using the internal dose metrics. Third, a human PBPK model was used to estimate
      the daily mg kg-1 dose that would produce the same internal dose metric in both
      normal and susceptible humans. Mechanistic research into the mode of action for
      Cr(VI)-induced intestinal tumors in mice supports a threshold mechanism involving
      intestinal wounding and chronic regenerative hyperplasia. As such, an RfD was
      developed using incidence data for the precursor lesion diffuse epithelial
      hyperplasia. This RfD was compared to RfDs for other non-cancer endpoints; all
      RfD values ranged 0.003-0.02 mg kg-1  day-1 . The lowest of these values is
      identical to EPA's existing RfD value. Although the RfD value remains 0.003 mg kg
      1  day-1 , the confidence is greatly improved due to the use of a 2-year
      bioassay, mechanistic data, PBPK models and benchmark dose modeling.

PMID- 29064109
TI  - Single determinant N-representability and the kernel energy method applied to
      water clusters.
AB  - The Kernel energy method (KEM) is a quantum chemical calculation method that has
      been shown to provide accurate energies for large molecules. KEM performs
      calculations on subsets of a molecule (called kernels) and so the computational
      difficulty of KEM calculations scales more softly than full molecule methods.
      Although KEM provides accurate energies those energies are not required to
      satisfy the variational theorem. In this article, KEM is extended to provide a
      full molecule single-determinant N-representable one-body density matrix. A
      kernel expansion for the one-body density matrix analogous to the kernel
      expansion for energy is defined. This matrix is converted to a normalized
      projector by an algorithm due to Clinton. The resulting single-determinant N
      representable density matrix maps to a quantum mechanically valid wavefunction
      which satisfies the variational theorem. The process is demonstrated on clusters
      of three to twenty water molecules. The resulting energies are more accurate than
      the straightforward KEM energy results and all violations of the variational
      theorem are resolved. The N-representability studied in this article is
      applicable to the study of quantum crystallography. (c) 2017 Wiley Periodicals,
      Inc.

PMID- 29064107
TI  - Cardiomyopathy syndrome in Atlantic salmon Salmo salar L.: A review of the
      current state of knowledge.
AB  - Cardiomyopathy syndrome (CMS) is a severe cardiac disease affecting Atlantic
      salmon Salmo salar L. The disease was first recognized in farmed Atlantic salmon
      in Norway in 1985 and subsequently in farmed salmon in the Faroe Islands,
      Scotland and Ireland. CMS has also been described in wild Atlantic salmon in
      Norway. The demonstration of CMS as a transmissible disease in 2009, and the
      subsequent detection and initial characterization of piscine myocarditis virus
      (PMCV) in 2010 and 2011 were significant discoveries that gave new impetus to the
      CMS research. In Norway, CMS usually causes mortality in large salmon in
      ongrowing and broodfish farms, resulting in reduced fish welfare, significant
      management-related challenges and substantial economic losses. The disease thus
      has a significant impact on the Atlantic salmon farming industry. There is a need
      to gain further basic knowledge about the virus, the disease and its
      epidemiology, but also applied knowledge from the industry to enable the
      generation and implementation of effective prevention and control measures. This
      review summarizes the currently available, scientific information on CMS and PMCV
      with special focus on epidemiology and factors influencing the development of
      CMS.

PMID- 29064110
TI  - Colectomy prior to diagnosis of primary sclerosing cholangitis is associated with
      improved prognosis in a nationwide cohort study of 2594 PSC-IBD patients.
AB  - BACKGROUND: Despite the close relationship between primary sclerosing cholangitis
      (PSC) and inflammatory bowel disease (IBD), the association between colectomy and
      the prognosis of PSC remains controversial. AIM: To explore whether colectomy
      prior to PSC-diagnosis is associated with transplant-free survival. METHODS: A
      nationwide cohort study in Sweden including all patients aged 18 to 69 years in
      whom both PSC and IBD was diagnosed between 1987 and 2014 was undertaken. Each
      patient was followed from date of both PSC and IBD diagnoses until liver
      transplantation or death, or 31 December 2014. Patients with colon in situ, and
      colectomy prior to PSC-diagnosis were compared. Survival analyses were performed
      using the Kaplan-Meier method and multivariable Cox regression models. RESULTS:
      Of the 2594 PSC-IBD patients, 205 patients were treated with colectomy before PSC
      diagnosis. During follow-up, liver transplantations were performed in 327
      patients and 509 died. The risk of liver transplantation or death was lower in
      patients treated with colectomy prior to PSC-diagnosis (HR 0.71, 95% CI 0.53
      0.95) than in patients with colon in situ. Male gender, longer time between IBD
      and PSC-diagnosis and older age were all associated with an increased risk of
      liver transplantation or death. Colectomy after PSC-diagnosis was however not
      associated with an increased risk of liver transplantation or death during long
      term follow-up. CONCLUSIONS: In PSC-IBD patients, colectomy prior to PSC
      diagnosis is associated with a decreased risk of liver transplantation or death.

PMID- 29064111
TI  - Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid
      Elasticity in Pediatric Patients With Hashimoto Thyroiditis.
AB  - OBJECTIVES: To evaluate the parenchymal elasticity of the thyroid gland with
      acoustic radiation force impulse imaging in pediatric patients with Hashimoto
      thyroiditis and to compare it with healthy volunteers. METHODS: Twenty-six
      patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17
      years were included. The shear wave velocity (SWV) values of both thyroid lobes
      in both groups were evaluated. RESULTS: The age and sex characteristics of the
      controls and patients with Hashimoto thyroiditis were similar. The SWV of the
      thyroid gland in patients with Hashimoto thyroiditis (mean +/- SD, 1.67 +/- 0.63
      m/s) was significantly higher than that in the control group (1.30 +/- 0.13 m/s;
      P < .001). There was no significant difference between the thyroid lobes in both
      groups. A receiver operating characteristic curve analyses showed an optimal
      cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 %
      positive predictive value, and a 75.0% negative predictive value (area under the
      curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a
      positive correlation between the SWV values versus anti-thyroperoxidase (Pearson
      r = 0.46; P = .038). There were no correlations between age, body mass index,
      thyroid function test results, and anti-thyroglobulin values and versus SWV
      values. Also, no significant differences were seen between the groups for gland
      size, gland vascularity, and l-thyroxine treatment. CONCLUSIONS: Acoustic
      radiation force impulse elastography showed a significant difference in the
      stiffness of the thyroid gland between children with Hashimoto thyroiditis and
      the healthy group. Using acoustic radiation force impulse elastography
      immediately after a standard ultrasound evaluation may predict chronic autoimmune
      thyroiditis.

PMID- 29064112
TI  - Contribution of 3-Dimensional Contrast-Enhanced Ultrasonography (CEUS) Compared
      With 2-Dimensional CEUS in the Analysis of Liver Tumors.
AB  - OBJECTIVES: In this study, we investigated the vascular characteristics of liver
      tumors on 3-dimensional (3D) and 2-dimensional (2D) contrast-enhanced
      ultrasonography (CEUS). The clinical value of these CEUS methods in the diagnosis
      of benign and malignant liver tumors was evaluated and compared. METHODS: A total
      of 126 liver tumors were examined by conventional ultrasonography (US), 2D CEUS,
      and dynamic 3D CEUS (frequency range, 1-6 MHz; focusing ability, 2-25 cm in
      depth; mechanical index, 0.09). Dynamic 3D CEUS images were postprocessed with
      high-resolution intelligent tomographic technology. The sensitivity and
      specificity of the CEUS methods in differentiating benign and malignant liver
      tumors were compared, as were the vascular characteristics (including the number
      and spatial relationships of the tumor vessels, such as origin and continuity) of
      the tumors in the arterial phase. RESULTS: The imaging methods did not
      significantly differ in their sensitivity and specificity for differentiating
      benign and malignant liver tumors (P > .05). Dynamic 3D CEUS was significantly
      better than 2D CEUS in revealing the vascular characteristics of the tumors (P <
      .05). The vascular morphologic characteristics of benign and malignant hepatic
      tumors in the arterial phase of dynamic 3D CEUS using intelligent tomographic
      technology differed significantly (P < .05). CONCLUSIONS: Dynamic 3D CEUS of
      liver tumors provides a more intuitive and comprehensive view of the spatial
      relationships of their blood vessels, including their peripheral and internal
      distribution. The volume information obtained with dynamic 3D CEUS combined with
      intelligent tomographic technology can improve the US-based diagnosis of liver
      tumors and thus guide their treatment.

PMID- 29064113
TI  - Genetic parameters for resistance against Flavobacterium columnare in Nile
      tilapia Oreochromis niloticus (Linnaeus, 1758).
AB  - Columnaris disease is a major cause of mortality in tilapia hatcheries and
      commonly occurs during the summer season in Thailand. One way of reducing the
      problem is by selective breeding for increased disease resistance. The objective
      of this study was to estimate quantitative genetic parameters for resistance
      against columnaris in the Chitralada 4 strain of Nile tilapia. Data from 43 full
      sib families (2,580 records) of fry (age = 32 +/- 4 days post-hatch) were used in
      the analyses. Initially, fry were subjected to bath challenge with Flavobacterium
      columnare (LD50 concentration = 1.2 * 106  CFU/ml) for 14 days. Disease
      resistance was defined as the number of days from challenge until death (DD) or
      as a binary trait (dead/alive) on day 14. Linear animal and sire-dam models were
      used for DD, while threshold animal, threshold sire-dam, binary linear animal and
      binary linear sire-dam models were used for binary outcomes. Covariate effect of
      age, fixed effect of challenge day and random effects of the individual animals
      or sires and dams were included in the models. Mean survival was 32.4 +/- 11.6%,
      and survival rates of the best and poorest families were 70% and 8%,
      respectively. The highest estimate of heritability (0.30 +/- 0.025) was obtained
      under the threshold sire-dam model. Heritability estimates for DD (0.16 +/- 0.034
      and 0.17 +/- 0.046) were comparable to those obtained from the threshold animal
      (0.15 +/- 0.031) and the binary linear (0.14 +/- 0.045 and 0.15 +/- 0.044)
      models. The linear animal and sire-dam models for DD and the threshold sire-dam
      models performed equally with similar values of rEBV (0.629, 0.628 and 0.627) and
      accuracy of selection (0.793, 0.793 and 0.791). This study reveals the potential
      of selective breeding to increase disease resistance to F. columnare in the
      studied population of Nile tilapia.

PMID- 29064114
TI  - Invasive squamous cell carcinoma: comparison of differentiation grade and tumour
      depth by anatomical site in 1666 tumours.
AB  - BACKGROUND: Invasive squamous cell carcinomas (SCCs) presents with different
      grades of differentiation and depths of invasion. AIM: To compare the grade of
      differentiation, tumour diameter and tumour depth by anatomical site in invasive
      SCC. METHODS: Retrospective clinical and histopathological data on consecutive
      cases of SCC came from a clinic in Sydney, Australia were assessed. A multinomial
      logistic regression model was applied to compare grades of differentiation by
      age, sex, anatomical sites, and histological tumour maximum diameter and depth.
      RESULTS: In total, 1666 SCCs were identified, including 82.1% (n = 1367) well
      differentiated, 13.3% (n = 222), moderately differentiated and 4.6% (n = 77)
      poorly differentiated SCCs. Patients with poorly differentiated tumours were more
      likely to be older and male (both P < 0.001). The most common site for poor
      differentiation was the scalp in men (n = 12; 15.6%) and the cheek or chin in
      women (n = 7; 9.1%). In the multivariate model, compared with well-differentiated
      SCC, older age was significantly associated with poorly and moderately
      differentiated SCC (P < 0.01 and P = 0.02, respectively). Larger tumour diameters
      were related to poor differentiation (P = 0.03). Ear, forehead and chest sites
      had increased tumour depth and poor differentiation. CONCLUSIONS: This study
      found increased rates of poorly differentiated SCC on the forehead and cheek for
      both sexes, while men displayed increased rates of poorly differentiated SCC on
      the bald scalp and the ears. Tumour diameter and depth increased as tumours
      varied from well-differentiated to moderately differentiated and from moderately
      differentiated to poorly differentiated. An increase in depth and increased
      prevalence of poorly differentiated tumours were found on the ears for men and on
      various facial sites for both sexes.

PMID- 29064115
TI  - Living with disasters: social capital for disaster governance.
AB  - This paper explores how social networks and bonds within and across organisations
      shape disaster operations and strategies. Local government disaster training
      exercises serve as a window through which to view these relations, and 'social
      capital' is used as an analytic for making sense of the human relations at the
      core of disaster management operations. These elements help to expose and
      substantiate the often intangible relations that compose the culture that exists,
      and that is shaped by preparations for disasters. The study reveals how this
      social capital has been generated through personal interactions, which are shared
      among disaster managers across different organisations and across 'levels' within
      those organisations. Recognition of these 'group resources' has significant
      implications for disaster management in which conducive social relations have
      become paramount. The paper concludes that socio-cultural relations, as well as a
      people-centred approach to preparations, appear to be effective means of readying
      for, and ultimately responding to, disasters.

PMID- 29064116
TI  - 'Faith can come in, but not religion': secularity and its effects on the disaster
      response to Typhoon Haiyan.
AB  - While other works have analysed what constitutes a faith-based approach, this
      study examines what values and practices are employed in a secular approach to
      disaster response in communities where religion matters. Evidence of a secular
      approach is assessed in the context of the disaster response to Typhoon Haiyan
      (2013) in the Philippines, a country in which more than 90 per cent of the
      population identify themselves as religious. Using interviews with staff members
      of non-governmental organisations (NGOs) and focus groups composed of
      beneficiaries, this paper provides an overview of how respondents commonly
      characterise a secular approach to disaster response. Results indicate differing
      NGO and beneficiary opinions on interaction over efficiency and the impartiality
      and neutrality of organisations. Secularity had a distinct effect on the disaster
      response to Haiyan, mostly by creating boundaries vis-a-vis when and where
      religion was permitted in the secularised humanitarian system. An awareness of
      these effects is encouraged to improve interaction with affected populations and
      local organisations.

PMID- 29064118
TI  - UK multicentre audit of the management of eczema in children.

PMID- 29064117
TI  - Correlation Between the Thymic-Thoracic Ratio and Cardiac Axis in Healthy
      Fetuses.
AB  - OBJECTIVES: The aim of this study was to assess the correlation between the
      thymic-thoracic ratio and cardiac axis in healthy fetuses. METHODS: The fetal
      thymic-thoracic ratio and cardiac axis were measured in 220 healthy fetuses. The
      normal ranges of the fetal thymic-thoracic ratio and cardiac axis for each
      gestational week were established. The Pearson correlation coefficient was
      calculated to analyze the relationship between the thymic-thoracic ratio and
      cardiac axis. RESULTS: The mean fetal thymic-thoracic ratio increased slightly
      throughout the pregnancy, from 0.33 at 17 weeks' gestation to 0.37 at 37 weeks.
      No statistically significant correlation was found between the thymic-thoracic
      ratio and cardiac axis in healthy fetuses. CONCLUSIONS: In healthy fetuses, the
      thymus occupies an increasingly larger portion of the upper mediastinum when the
      pregnancy advances. The cardiac axis is not affected by the thymic-thoracic ratio
      in healthy fetuses.

PMID- 29064119
TI  - In chronic spontaneous urticaria, high numbers of dermal endothelial cells, but
      not mast cells, are linked to recurrent angio-oedema.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder
      characterized by recurrent weals, angio-oedema or both. Recent studies have shown
      that the number of endothelial cells is increased in the skin of patients with
      CSU, but the underlying mechanisms and clinical implications of this are unclear.
      AIM: To evaluate whether mast cell (MC) or endothelial cell (EC) numbers
      correlate with CSU and whether they are relevant for disease duration, disease
      activity or the presence of clinical features. METHODS: We determined the numbers
      of CD31+ ECs and MCs in nonlesional skin of 30 patients with CSU using
      quantitative histomorphometry, and assessed their correlation with each other and
      with clinical features such as disease duration, disease activity and occurrence
      of angio-oedema. RESULTS: The numbers of MCs and ECs were high in the nonlesional
      skin of patients with CSU, but did not correlate with each other. Neither MC
      number nor EC number correlated with disease duration or disease activity.
      Interestingly, patients with high numbers of cutaneous CD31+ ECs had higher rates
      of recurrent angio-oedema and vice versa. CONCLUSIONS: Based on these findings,
      we speculate that vascular remodelling and MC hyperplasia in patients with CSU
      occurs independently and via different mechanisms. Targeting of the mechanisms
      that drive neoangiogenesis in CSU may result in novel therapeutic strategies for
      the management of patients with angio-oedema.

PMID- 29064120
TI  - Prospects of Contrast-Enhanced Ultrasonography for the Diagnosis of Peripheral
      Arterial Disease: A Meta-analysis.
AB  - OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) is a modern diagnostic
      method that can also be used to study microperfusion. This study compared the
      time to peak intensity measured by CEUS in patients with peripheral arterial
      disease (PAD) and healthy control participants. METHODS: After a comprehensive
      literature search in multiple electronic databases and study selection, a random
      effect meta-analysis was performed to compare the time to peak intensity measured
      by CEUS in patients with PAD and healthy controls, which followed meta-regression
      analyses for identification of factors affecting the outcomes. RESULTS: Fourteen
      studies (data for 322 patients with PAD and 314 healthy individuals) were used
      for the meta-analysis. The age of this sample of patients with PAD was 64.92 (95%
      confidence interval, 62.53, 67.31) years, and that of the healthy controls was
      55.32 (51.67, 58.98) years. The times to peak intensity were 18.55 (15.62, 21.48)
      seconds in healthy controls, 33.40 (27.65, 39.15) seconds in patients with PAD,
      and 76.22 (36.23, 116.22) seconds in patients with PAD and diabetes mellitus. The
      difference between patients with PAD and healthy controls in the time to peak
      intensity was statistically significant (mean difference, 24.80 [10.16, 39.44]
      seconds; P < .00009). The ABI was not significantly associated with the time to
      peak intensity in patients with PAD. Age and sex were also not significantly
      associated with the time to peak intensity. CONCLUSIONS: Contrast-enhanced
      ultrasonography is a valuable tool for the diagnosis of PAD based on its ability
      to differentiate the time to peak intensity between patients with PAD and healthy
      individuals, but little data are yet available to assess its diagnostic ability
      in clinical practice.

PMID- 29064121
TI  - U-stitches in microvascular anastomosis in an animal model.

PMID- 29064122
TI  - Using linear cutting stapler for gracillis muscle flap splitting in facial
      reanimation.

PMID- 29064124
TI  - Toward a New Generation of Smart Biomimetic Actuators for Architecture.
AB  - Motile plant structures (e.g., leaves, petals, cone scales, and capsules) are
      functionally highly robust and resilient concept generators for the development
      of biomimetic actuators for architecture. Here, a concise review of the state-of
      the-art of plant movement principles and derived biomimetic devices is provided.
      Achieving complex and higher-dimensional shape changes and passive-hydraulic
      actuation at a considerable time scale, as well as mechanical robustness of the
      motile technical structures, is challenging. For example, almost all currently
      available bioinspired hydraulic actuators show similar limitations due to the
      poroelastic time scale. Therefore, a major challenge is increasing the system
      size to the meter range, with actuation times of minutes or below. This means
      that response speed and flow rate need significant improvement for the systems,
      and the long-term performance degradation issue of hygroscopic materials needs to
      be addressed. A theoretical concept for "escaping" the poroelastic regime is
      proposed, and the possibilities for enhancing the mechanical properties of
      passive-hydraulic bilayer actuators are discussed. Furthermore, the promising
      aspects for further studies to implement tropistic movement behavior are
      presented, i.e., movement that depends on the direction of the triggering
      stimulus, which can finally lead to "smart building skins" that autonomously and
      self-sufficiently react to changing environmental stimuli in a direction
      dependent manner.

PMID- 29064123
TI  - In vitro antifungal activity of amphotericin B and 11 comparators against
      Aspergillus terreus species complex.
AB  - Aspergillus terreus infections are difficult to treat because of the intrinsic
      resistance to amphotericin B, and higher mortality compared to infections caused
      by other Aspergillus species. The aim of the present study was to determine the
      in vitro antifungal activity of amphotericin B and 11 comparators against
      clinical (n = 36) and environmental (n = 45) A. terreus isolates. In vitro
      antifungal susceptibility was performed using the CLSI M38-A2 procedure.
      Amphotericin B exhibited the highest MICs (MIC range, 0.125-4 MUg/mL; MIC90 , 2
      MUg/mL), followed by terbinafine (MIC range, 0.002-1 MUg/mL; MIC90 , 1 MUg/mL).
      Only one isolate (1/81) showed amphotericin B MIC above the epidemiologic cut-off
      value (ECV; 4 MUg/mL). None of the isolates had a MIC of >= ECV for voriconazole,
      itraconazole and posaconazole. The reasons for the difference in amphotericin B
      susceptibility patterns between studies remain unknown. The genetic and species
      diversity, clinical, environmental and ecological factors in Terrei section on
      various amphotericin B susceptibility profiles in different countries should be
      considered more as the main reasons associated with these differences.

PMID- 29064125
TI  - Fluorescence Correlation Spectroscopy of Labeled Azurin Reveals Photoinduced
      Electron Transfer between Label and Cu Center.
AB  - Fluorescent labeling of biomacromolecules enjoys increasing popularity for
      structural, mechanistic, and microscopic investigations. Its success hinges on
      the ability of the dye to alternate between bright and dark states. Forster
      resonance energy transfer (FRET) is an important source of fluorescence
      modulation. Photo-induced electron transfer (PET) may occur as well, but is often
      considered only when donor and acceptor are in van der Waals contact. In this
      study, PET is shown between a label and redox centers in oxidoreductases, which
      may occur over large distances. In the small blue copper protein azurin, labeled
      with ATTO655, PET is observed when the label is at 18.5 A, but not when it is at
      29.1 A from the Cu. For CuII , PET from label to Cu occurs at a rate of (4.8+/
      0.3)*104  s-1 and back at (0.7+/-0.1)*103  s-1 . With CuI the numbers are (3.3+/
      0.7)*106  s-1 and (1.0+/-0.1)*104  s-1 . Reorganization energies and electronic
      coupling elements are in the range of 0.8-1.2 eV and 0.02-0.5 cm-1 ,
      respectively. These data are compatible with electron transfer (ET) along a
      through-bond pathway although transient complex formation followed by ET cannot
      be ruled out. The outcome of this study is a useful guideline for experimental
      designs in which oxidoreductases are labelled with fluorescent dyes, with
      particular attention to single molecule investigations. The labelling position
      for FRET can be optimized to avoid reactions like PET by evaluating the structure
      and thermodynamics of protein and label.

PMID- 29064126
TI  - Microporous Organic Materials for Membrane-Based Gas Separation.
AB  - Membrane materials with excellent selectivity and high permeability are crucial
      to efficient membrane gas separation. Microporous organic materials have evolved
      as an alternative candidate for fabricating membranes due to their inherent
      attributes, such as permanent porosity, high surface area, and good
      processability. Herein, a unique pore-chemistry concept for the designed
      synthesis of microporous organic membranes, with an emphasis on the relationship
      between pore structures and membrane performances, is introduced. The latest
      advances in microporous organic materials for potential membrane application in
      gas separation of H2 , CO2 , O2 , and other industrially relevant gases are
      summarized. Representative examples of the recent progress in highly selective
      and permeable membranes are highlighted with some fundamental analyses from pore
      characteristics, followed by a brief perspective on future research directions.

PMID- 29064127
TI  - Second-generation cryoballoon ablation for treatment of persistent atrial
      fibrillation: Three-year outcome and predictors of recurrence after a single
      procedure.
AB  - INTRODUCTION: Data on long-term outcomes of cryoballoon (CB) ablation for
      treatment of persistent atrial fibrillation (AF) are sparse. Here, we report the
      first 3-year follow-up results and predictors of success for catheter ablation
      using the second-generation CB in patients with persistent AF. METHODS AND
      RESULTS: For this prospective observational study, we enrolled 101 patients
      ablated with the second-generation CB at our institution. The endpoint was the
      first documented recurrence (> 30 seconds) of AF, atrial flutter, or atrial
      tachycardia after a 3-month blanking period. Follow-up data were collected during
      outpatient clinic visits and included Holter-ECG recordings. The impact of
      several variables on recurrence was evaluated by means of univariate and
      multivariate analyses and Cox proportional hazards regression models. After a
      median follow-up of 37 (31 of 42) months, recurrence was documented in 30
      patients (29.7%). The median procedure and fluoroscopy times were 120 (102 of
      147) and 20 (16 of 27) minutes, respectively. Phrenic nerve palsy occurred in
      2.0% of the patients. Among the 30 patients who experienced recurrence, 16
      underwent repeat ablation in radiofrequency technique. Cox regression analysis
      showed that left atrial area > 21 cm2 and AF history duration > 2 years
      independently predicted recurrence. CONCLUSIONS: Sinus rhythm was maintained in a
      substantial proportion of patients even 3 years after CB ablation. Patients with
      a nonenlarged left atrium and short AF history had the best outcome.

PMID- 29064128
TI  - The Association Between Change in Serum Bicarbonate and Change in Thyroid Hormone
      Levels in Patients Receiving Conventional or More Frequent Maintenance
      Hemodialysis.
AB  - AIM: Correction of metabolic acidosis in patients with chronic kidney disease has
      been associated with improvement in thyroid function. We examined whether changes
      in bicarbonate were associated with changes in thyroid function in patients with
      end-stage renal disease receiving conventional or more frequent hemodialysis.
      METHODS: In the Frequent Hemodialysis Network Trials, the relationship between
      changes in serum bicarbonate, free triiodothyronine (FT3) and free thyroxine
      (FT4) was examined among 147 and 48 patients with endogenous thyroid function who
      received conventional (3x/week) or more frequent (6x/week) hemodialysis (Daily
      Trial) or who received conventional or more frequent nocturnal hemodialysis
      (Nocturnal Trial). Equilibrated normalized protein catabolic rate (enPCR) was
      examined to account for nutritional factors affecting both acid load and thyroid
      function. RESULTS: Increasing dialysis frequency was associated with increased
      bicarbonate level. Baseline bicarbonate level was not associated with baseline
      FT3 and FT4. Change in bicarbonate level was not associated with changes in FT3
      and FT4 in the Daily Trial nor for FT4 in the Nocturnal Trial (r<=0.14, P>0.21).
      While, a significant correlation between change in serum bicarbonate and change
      in FT3 (r=0.44, P=0.02) was observed in the Nocturnal Trial; findings were no
      longer significant after adjusting for change in enPCR (r=0.37, P=0.08). For
      participants with baseline bicarbonate <23mMol/L, no association between change
      in bicarbonate and change in thyroid indices were seen in the Daily Trial; for
      the Nocturnal Trial, findings were also not significant for change in FT3 and the
      association between change in bicarbonate and change in FT4 (r=0.54, P=0.03) was
      no longer significant after adjusting for enPCR (r=0.45, P=0.11). CONCLUSIONS:
      Changes in bicarbonate were not associated with changes in thyroid hormone levels
      after adjusting for enPCR, as a marker of nutritional status. Future studies
      should examine whether improvement in acid base status improves thyroid function
      in hemodialysis patients with evidence of thyroid hypofunction.

PMID- 29064129
TI  - Validating Nonlinear Registration to Improve Subtraction Images for Lesion
      Detection and Quantification in Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: To propose and validate nonlinear registration techniques
      for generating subtraction images because of their ability to reduce artifacts
      and improve lesion detection and lesion volume quantification. METHODS:
      Postcontrast T1 -weighted spin echo and T2 -weighted dual echo images were
      acquired for 20 patients with relapsing-remitting multiple sclerosis (RRMS) on a
      monthly basis for a year (14 women, average age 33.6 +/- 6.9). The T2 -weighted
      images from the first scan were used as a baseline for each patient. The images
      from the last scan were registered to the baseline image. Four different
      registration algorithms used for evaluation included; linear, halfway linear,
      nonlinear, and nonlinear halfway. Subtraction images were generated after brain
      extraction, intensity normalization, and Gaussian blurring. Lesion activity
      changes along with identified artifacts were scored on all four techniques by two
      independent observers. Additionally, quantitative analysis of the algorithms was
      performed by estimating the volume changes of simulated lesions and real lesions.
      For real lesion volume change analysis, five subjects were selected randomly.
      Subtraction images were generated between all the 11 time points and the baseline
      image using linear and nonlinear registration for the five subjects. RESULTS:
      Lesion activity detection resulted in similar performance among the four
      registration techniques. Lesion volume measurements on subtraction images using
      nonlinear registration were closer to lesion volume on T2 -weighted images. A
      statistically significant difference was observed among the four registration
      techniques while evaluating yin-yang artifacts. Pairwise comparisons showed that
      nonlinear registration results in the least amount of yin-yang artifacts, which
      are significantly different. CONCLUSIONS: Nonlinear registration for generation
      of subtraction images has been demonstrated to be a promising new technique as it
      shows improvement in lesion activity change detection. This approach decreases
      the number of artifacts in subtraction images. With improved lesion volume
      estimates and reduced artifacts, nonlinear registration may lead to discarding
      less subject data and an improvement in the statistical power of subtraction
      imaging studies.

PMID- 29064131
TI  - Responsibility of the doctor who prescribes serotonin and noradrenaline reuptake
      inhibitors for patients with chronic musculoskeletal pain.

PMID- 29064132
TI  - Evaluation of the influence of time and concentration of sodium hypochlorite on
      the bond strength of glass fibre post.
AB  - This study evaluated the effect of time and concentrations of sodium hypochlorite
      on the bond strength of a glass fibre post cemented in a root canal with resin
      cement. A total of 45 single-rooted extracted human teeth were prepared with
      Protaper(r) universal files, randomly allocated into nine groups and then
      subjected to 1% or 4% NaOCl for a period of 1 min or 2 min. Fibre posts were then
      bonded into the root canal, sectioned and the bond strength tested using a push
      out test. A longer irrigation time resulted in a significant reduction (P < 0.05)
      in bond strength, while a final additional irrigation with distilled water
      significantly reduced bond strength. The concentration of NaOCl did not
      significantly affect bond strength. Within the limitations of this study, it was
      observed that regardless of the concentration of NaOCl used, shorter irrigation
      times favoured better fibre post bonding.

PMID- 29064130
TI  - Use of cell surface protein typing for genotyping of azole-resistant and 
      susceptible Aspergillus fumigatus isolates in Iran.
AB  - Aspergillus fumigatus is the leading cause of mortality in severely
      immunocompromised individuals. Understanding pathogen dispersion and relatedness
      is essential for determining the epidemiology of nosocomial infections.
      Therefore, the aim of this study was to investigate the diversity and putative
      origins of clinical and environmental azole-susceptible and -resistant A.
      fumigatus isolates from Iran. In all, 79 isolates, including 64 azole-susceptible
      and 15 -resistant isolates, were genotyped using the cell surface protein (CSP)
      gene. Seven distinct repeat types (r01, r02, r03, r04, r05, r06 and r07) and 11
      different CSP variants (t01, t02, t03, t04A, t06A, t06B, t08, t10, t18A, t18B and
      t22) were observed. Interestingly, t06B, t18A and t18B were exclusively present
      in azole-resistant isolates. The Simpson's index of diversity (D) was calculated
      at 0.78. Resistant isolates were genetically less diverse than azole-susceptible
      isolates. However, azole-resistant A. fumigatus without TR34 /L98H were more
      diverse than with TR34 /L98H. The limited CSP type diversity of the TR34 /L98H
      isolates versus azole-susceptible isolates suggests that repeated independent
      emergence of the TR34 /L98H mechanism is unlikely. It has been suggested that CSP
      types might have a common ancestor that developed locally and subsequently
      migrated worldwide.

PMID- 29064134
TI  - Reducing radiation exposure during procedures performed in the electrophysiology
      laboratory.
AB  - INTRODUCTION: Expert societies recently published strong recommendations to
      reduce the exposure of patients and staff to ionizing radiation (IR) during
      interventional and electrophysiology (EP) procedures. However, adherence to these
      guidelines remains difficult and the impact of implementing such recommendations
      is poorly characterized. METHODS AND RESULTS: We conducted a single-center cohort
      study to quantify radiation exposure over time in three EP laboratories at the
      Montreal Heart Institute during 5,546 consecutive procedures from 2012 to 2015 by
      11 primary operators. Overall, 2,618 (47.2%) procedures were catheter-based and
      2,928 (52.8%) were device interventions. Interventions to reduce radiation
      exposure included educational initiatives to raise awareness (i.e., limiting cine
      acquisition, patient position, table height), slower frame rate, lower radiation
      dose per pulse, collimation, and integration with 3-D mapping systems and/or
      MediGuide technology. An 85% reduction in IR exposure was observed from 2012 to
      2015, with the mean dose-area-product (DAP) decreasing from 7.65 +/- 0.05 Gy.cm2
      to 1.15 +/- 0.04 Gy.cm2 (P < 0.001). This was true for catheter-based procedures
      (mean DAP 16.99 +/- 0.08 to 2.00 +/- 0.06 Gy.cm2 , P < 0.001) and device
      interventions (mean DAP 4.18 +/- 0.06 to 0.64 +/- 0.05 Gy.cm2 , P < 0.001). The
      median effective dose of IR recorded per quarter by 282 cervical dosimeters on EP
      staff decreased from 0.57 (IQR 0.18, 1.03) mSv in 2012 to 0.00 (IQR 0.00, 0.19)
      mSv in 2015, P < 0.001. CONCLUSION: Enforcing good clinical practices with simple
      measures and low-dose fluoroscopy settings are highly effective in reducing IR
      exposure in the EP lab. These promising results should encourage other EP labs to
      adopt similar protective measures.

PMID- 29064135
TI  - Approaches for Selective Synthesis of Ullazine Donor-Acceptor Systems.
AB  - Methods for effective synthesis for the four possible isomeric 3,9
      diphenylullazine carboxaldehydes and reactive halogen intermediates are
      described. Ullazine donor-acceptor (D-A) dyes were studied using UV/Vis,
      photoluminescence (PL) spectroscopy and cyclic voltammetry. X-ray single crystal
      diffraction analysis independently confirmed the structures of two key
      intermediates. A D-A dye based on ullazine with dihexylmalonate acceptor was
      tested as a dopant-free hole-transporting material (HTM) in a perovskite solar
      cell, exhibiting promising power conversion efficiency (PCE) reaching 13.07 %.

PMID- 29064133
TI  - "Double carbapenem" and oral fosfomycin for the treatment of complicated urinary
      tract infections caused by blaNDM -harboring Enterobacteriaceae in kidney
      transplantation.
AB  - Infections with carbapenemase-producing carbapenem-resistant Enterobacteriaceae
      represent an emergent problem worldwide. Treatment of infections caused by New
      Delhi metallo-beta-lactamase (NDM)-harboring Enterobacteriaceae is particularly
      challenging as it frequently involves the use of nephrotoxic agents, which is
      problematic in kidney transplant recipients and non-renal transplant patients
      with marginal kidney function. We present two cases of urinary tract infections
      caused by NDM-harboring Enterobacteriaceae successfully treated with a
      combination of "double carbapenem" and oral fosfomycin.

PMID- 29064137
TI  - Diffusion Tensor Imaging Shows Corpus Callosum Differences between High-Grade
      Gliomas and Metastases.
AB  - BACKGROUND AND PURPOSE: The corpus callosum (CC) has an important role in
      regulating interhemispheric transfer and is thought to be instrumental in
      contralateral brain reorganization in patients with brain tumors, as suggested by
      a previous study reporting callosal differences between language dominance groups
      through diffusion tensor imaging (DTI) characteristics. The purpose of this study
      was to explore the structural differences in the CC between high-grade gliomas
      (HGGs) and metastatic tumors (METs) using the DTI characteristics of fractional
      anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD). METHODS: HGG
      (n = 30) and MET (n = 20) subjects with Magnetic Resonance Imaging (MRI) scans
      including DTI were retrospectively studied. The tumor and CC were segmented using
      the 3-dimensional T1-weighted scans to determine their volumes. The region of
      interest (ROI; mean volume of the ROI = 3,090 +/- 464 mm3 ) of the body of the CC
      was overlaid onto the DTI parametric maps to obtain the averaged FA, MD, and AD
      values. RESULTS: There were significant differences in the distributions of FA
      and MD values between the two patient groups (mean FA for HGG/MET = .691/.646, P
      < .05; mean MD for HGG/MET = .894*10-3 mm 2/ second /.992*10-3 mm2 /second, P <
      .01), while there was no correlation between the DTI parameters and the
      anatomical volumes. CONCLUSION: These results suggest that there is more
      contralateral brain reorganization in HGG patients than MET patients and that
      neither the tumor nor callosal volume impact the degree of contralateral brain
      reorganization.

PMID- 29064136
TI  - Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress.
AB  - AIM: The aim of this clinical trial was to obtain proof of concept for high-dose
      pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl
      stress. METHODS: Ten Japanese schizophrenia patients with high plasma
      pentosidine, which is a representative biomarker of enhanced carbonyl stress,
      were recruited in a 24-week, open trial in which high-dose pyridoxamine (ranging
      from 1200 to 2400 mg/day) was administered using a conventional antipsychotic
      regimen. Main outcomes were the total change in Positive and Negative Syndrome
      Scale score and the Brief Psychiatric Rating Scale score from baseline to end of
      treatment at week 24 (or at withdrawal). RESULTS: Decreased plasma pentosidine
      levels were observed in eight patients. Two patients showed marked improvement in
      their psychological symptoms. A patient who harbors a frameshift mutation in the
      Glyoxalase 1 gene also showed considerable reduction in psychosis accompanied
      with a moderate decrease in plasma pentosidine levels. A reduction of greater
      than 20% in the assessment scale of drug-induced Parkinsonism occurred in four
      patients. Although there was no severe suicide-related ideation or behavior,
      Wernicke's encephalopathy-like adverse drug reactions occurred in two patients
      and were completely suppressed by thiamine supplementation. CONCLUSION: High-dose
      pyridoxamine add-on treatment was, in part, effective for a subpopulation of
      schizophrenia patients with enhanced carbonyl stress. Further randomized, placebo
      controlled trials with careful monitoring will be required to validate the
      efficacy of high-dose pyridoxamine for these patients.

PMID- 29064139
TI  - Psychometric properties of the Parental Feeding Behaviours Questionnaire for
      Indonesian parents of young children.
AB  - PURPOSE: The objective of this study was to test the psychometric properties of
      the Parental Feeding Behaviours Questionnaire (PFBQ) to measure feeding
      behaviours of Indonesian parents of toddlers (young children). METHODS: A total
      of 696 parents of toddlers were obtained by convenience sampling during September
      2013 to April 2014. To validate the PFBQ, confirmatory factor analysis and the
      contrasted group technique were conducted. Reliability of this instrument was
      examined by construct reliability and test-retest reliability. RESULTS: Results
      showed that the regression coefficients of all 56 indicators were statistically
      significant (P < 0.001). The contrasted group technique showed significantly
      different parental feeding behaviours between parents of well-nourished and
      malnourished toddlers (P = 0.047). The test-retest reliability of the PFBQ was
      acceptable (Pearson correlation = 0.644), and the construct reliability ranged
      from 0.88 to 0.96. CONCLUSIONS: The PFBQ is a valid and reliable instrument;
      however, more studies are required to identify acceptable tools to measure more
      culturally diverse range of parental feeding behaviours.

PMID- 29064138
TI  - Treatment of human polyomavirus-7-associated rash and pruritus with topical
      cidofovir in a lung transplant patient: Case report and literature review.
AB  - Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic
      superficial viral skin infection, which primarily impacts immunocompromised
      individuals. We report on a case of PVARP in a lung transplant recipient. Our
      patient developed symptoms 13 years after being on his immunosuppressive regimen,
      with an insidious course of progressive gray lichenification with marked islands
      of sparing and quality of life-altering pruritus. Treatment for PVARP is not
      established; however, topical cidofovir combined with immunomodulation may offer
      sustained therapeutic benefit.

PMID- 29064141
TI  - Role of dietary phosphate restriction in chronic kidney disease.
AB  - AIM: Patients with progressive chronic kidney disease (CKD) develop positive
      phosphate balance that is associated with increased cardiovascular risk and
      mortality. Modification of dietary phosphate is a commonly used strategy to
      improve outcomes but is complicated by the need for adequate dietary protein.
      Surprisingly, the evidence for patient-level benefits from phosphate restriction
      is tenuous, and the justification for using any phosphate binder for pre-dialysis
      patients is questionable. METHODS: The evidence for dietary phosphate
      modification was reviewed, along with the possible role of a smart phone
      application (app) that provides information on phosphate, sodium, potassium and
      nutrients in over 50 000 Australian foods. A pilot study of healthy participants
      assigned to dietetic advice and standard diet sheets, or dietetic advice, diet
      sheets and use of the smart phone app was performed. RESULTS: Following baseline
      studies, 25 participants commenced the sodium and phosphate restricted diet.
      After 2 weeks, both groups showed non-significant trends to reduction in urinary
      phosphate and sodium. App users referred to information on the app more
      frequently than the control group participants referred to written instructions,
      found referring to the app more convenient, felt they learned more new
      information, were more motivated to maintain the diet and were more likely to
      recommend their information source to family or friends (all P < 0.05).
      CONCLUSIONS: Maintaining phosphate balance remains an important goal of CKD
      management, although diets incorporating very low phosphate and protein contents
      may worsen patient outcomes. For selected patients, a smart phone app may improve
      dietary acceptance and compliance.

PMID- 29064140
TI  - Incidence and clinical profile of tuberculosis after allogeneic stem cell
      transplantation.
AB  - BACKGROUND: Patients post allogeneic stem cell transplantation (alloSCT) are
      expected to be at high risk of tuberculosis (TB) owing to underlying
      immunosuppression. We conducted a retrospective study in patients post alloSCT
      for clinical features and factors associated with TB. METHODS: Records of all
      patients transplanted from January 1, 2012 until December 31, 2015 were reviewed.
      Diagnosis of TB was considered if Mycobacterium tuberculosis was cultured from
      clinical samples or acid-fast bacilli (AFB) were demonstrated on
      histopathology/smears. A presumptive TB diagnosis was considered in the presence
      of signs and symptoms suggestive of TB with epithelioid cell granulomas, without
      AFB. RESULTS: In 175 eligible patients, TB was detected in 5 patients (pulmonary
      = 4, lymph node = 1), with incidence of 2.84% at median of 258 (157-639) days
      after transplantation. Cumulative incidence rate of TB among the patients
      undergoing alloSCT was calculated to be 1.9/100 person-years. Median duration of
      symptoms was 20 days till diagnosis was confirmed. All patients were started on
      four-drug anti-tubercular therapy (ATT) with clinical/radiological response in
      all. Two patients developed hepatotoxicity (transaminitis, n = 1;
      hyperbilirubinemia, n = 1) following ATT. Presence of chronic graft-versus-host
      disease (GVHD) (P = .008) and steroid-refractory GVHD (P = .001) was found to be
      significantly associated with TB. CONCLUSION: TB should be suspected in patients
      with unexplained fever post alloSCT. Active GVHD and ongoing
      immunosuppression/steroids are possible risk factors. Early diagnosis and
      treatment can salvage most patients. Hepatotoxicity following ATT is a potential
      concern.

PMID- 29064142
TI  - Parent-to-Parent support providers: How recruits are identified.
AB  - OBJECTIVE: To examine selection criteria for Parent-to-Parent support parents
      trained to provide support to other parents of children with disabilities.
      METHOD: Ten leaders of Parent-to-Parent programmes participated in telephone
      interviews to explore attributes associated with parents selected to be trained
      as support parents. RESULTS: Qualitative analysis reveals parents deemed "ready"
      to become support parents, build relationships, exhibit positivity, build
      capacities, have good communication skills and a future orientation and feel the
      need to give back. An additional set of attributes we have named, "red flags" are
      associated with parents not suitable to provide support are also presented.
      CONCLUSIONS: Parent-to-Parent support parents are informally identified by a set
      of characteristics that can be operationalized for screening purposes. Findings
      provide support for the positive influence of the peer support relationship and
      identify the need for a measure of parent "readiness" to assist in the
      recruitment of quality support parents for the Parent-to-Parent organization.

PMID- 29064143
TI  - Lesbian, gay, and bisexual (LGB) people's experiences of nursing health care: An
      emancipatory nursing practice integrative review.
AB  - AIM: To review current research on lesbian, gay, and bisexual (LGB) individuals'
      experience of nursing services from an emancipatory nursing practice framework.
      BACKGROUND: As LGB issues are marginalized in health care, it is important to
      understand LGB individuals' experiences of nursing. DESIGN: An integrative
      literature review using critical analysis based on an emancipatory nursing
      practice framework was conducted. DATA SOURCES: A search of all English nursing
      journals in the World of Science database was conducted. REVIEW METHODS:
      Established methods were used to search, identify, and appraise articles meeting
      the criteria of examining LGB individuals' experiences of nursing services,
      published in the years 2009 to 2015. Sixteen articles that met the inclusion
      criteria were identified independently by the two authors. Data were analysed
      using descriptive and critical phases of enquiry. RESULTS: Results show a nexus
      of experiences of exclusion and oppressive social norms. Our analytical framework
      highlighted absences in nursing practice. No research indicates that LGB people
      experience nurses as advocates or participatory health care processes.
      CONCLUSION: Standards, training, and systems need to be devised that ensure
      inclusionary nursing practices, that encourage nurses to act as advocates for LGB
      health care justice, and that allow LGB individual to participate in the
      development of health care policies and procedures.

PMID- 29064144
TI  - Treatment of self-poisoning at a tertiary-level hospital in Bangladesh: cost to
      patients and government.
AB  - OBJECTIVES: Approximately 10 000 people die from suicide annually in Bangladesh,
      many from pesticide poisoning. We aimed to estimate financial costs to patients
      and health services of treating patients with self-poisoning. METHODS: Data on
      direct costs to families, sources of funds for treatment and family wealth were
      collected prospectively over a one-month period in 2016 at the tertiary
      Chittagong Medical College Hospital, Bangladesh. Aggregate operational costs to
      the government were calculated using annual budget, bed occupancy and length-of
      stay data. RESULTS: Agrochemicals were the most common substances ingested
      (58.8%). Median duration of stay and of illness was 2 and 5 days, respectively.
      Median total cost to patients was conservatively estimated at US$ 98.40, highest
      in agrochemical poisoning (US$ 179.50), with the greatest cost due to medicines
      and equipment. Misdiagnosis as organophosphorus poisoning in 17.0% of
      agrochemical cases resulted in increased cost to patients. Only 51.9% of patients
      had indicators of wealth; 78.1% borrowed money to cover costs. Conservatively
      estimated median healthcare costs (US$ 21.30 per patient) were markedly lower
      than costs to patients. CONCLUSIONS: Cost to patients of treating a case of
      agrochemical poisoning was approximately three times the cost of one month's
      essential items basket. Incorrect diagnosis at admission costs families
      substantial sums of money and increased length of stay; it costs the national
      government an estimated US$ 80 428.80 annually. Widespread access to a list of
      pesticides used in self-poisoning plus greater focus on training doctors to
      better manage different forms of agrochemical poisoning should reduce the
      financial burden to patients and healthcare systems.

PMID- 29064145
TI  - The roles of adult siblings in the lives of people with severe intellectual and
      developmental disabilities.
AB  - BACKGROUND: Siblings of people with intellectual and developmental disabilities
      (IDD) often assume key roles to support their brothers and sisters. For people
      with more significant support needs, siblings may undertake additional roles and
      responsibilities throughout their lives. The purpose of the present study was to
      identify and describe the roles of adult siblings who have a brother or sister
      with severe IDD. METHOD: Seventy-nine adult siblings from 19 to 72 years of age
      completed an online survey with open-ended questions about the roles they play in
      their relationships with their brother or sister. RESULTS: Thematic analysis
      resulted in identification of several roles including caregiver, friend (social
      partner), advocate, legal representative, sibling (teacher/role model), leisure
      planner and informal service coordinator. CONCLUSION: Siblings assume key roles
      in the lives of people with IDD and need support from family and professionals to
      perform these roles.

PMID- 29064147
TI  - Anemia as very late-onset cytomegalovirus disease after kidney transplantation.
AB  - Very late-onset cytomegalovirus (CMV) disease after solid organ transplantation
      is not associated with classic risk factors; therefore, it does not follow a
      pattern of predictable appearance. A high index of suspicion is necessary to make
      an accurate diagnosis. Anemia has multiple etiologies among kidney transplanted
      recipients, and CMV could be one of them. We report the case of a kidney
      recipient with anemia refractory to treatment which proved to be secondary to
      extremely late CMV digestive disease.

PMID- 29064146
TI  - Short- and long-term evaluation of cognitive functions after electroconvulsive
      therapy in a Japanese population.
AB  - AIM: While electroconvulsive therapy (ECT) is a well-established, safe, and
      effective treatment for mental illnesses, the potential for adverse effects on
      cognitive functions remains controversial. We aimed to evaluate multiple
      cognitive functions in different time periods before and after ECT in a Japanese
      population. METHODS: A battery of five neurocognitive tests was administered to
      patients who underwent a course of ECT treatment at three time points: before,
      immediately after, and 4 weeks after ECT. RESULTS: A transient but significant
      decline in letter fluency function was observed immediately after ECT, but had
      recovered well by 4 weeks. We also observed a significant improvement in the
      trail-making task at 4 weeks after ECT. CONCLUSION: In a Japanese population,
      adverse effects of ECT on verbal fluency function-related and other cognitive
      impairments were transient. Over the longer term, we detected significant
      improvements in the performance of tasks that presumably reflected information
      processing speed and executive functions.

PMID- 29064148
TI  - The GDCh and Angewandte Chemie Celebrate the 150th Anniversary and a Change of
      Editor-in-Chief.
AB  - On September 10, 2017, the GDCh celebrated the anniversary of the founding of one
      of its predecessor organizations, and on September 11, to mark this anniversary
      an Angewandte Fest Symposium was held at the Freie Universitat Berlin. On October
      1, Neville Compton (middle) took over as Editor-in-Chief of Angewandte Chemie, a
      position held by Peter Golitz (left) for 35 years. The Editor-in-Chief change was
      commented on by Alois Furstner, chairman of the journal's Editorial Board.

PMID- 29064149
TI  - Risk manager formula for success: Influencing decision making.
AB  - Providing the ultimate decision makers with a quantitative risk analysis based on
      thoughtful assessment by the organization's experts enables an efficient
      decision.

PMID- 29064150
TI  - Case law update.

PMID- 29064151
TI  - The underlying narrative of risk management.

PMID- 29064152
TI  - Curing hepatitis C virus (HCV) after organ transplantation: Increased risk of
      rejection following HCV elimination.

PMID- 29064153
TI  - Comparison of albumin, colloid osmotic pressure, von Willebrand factor, and
      coagulation factors in canine cryopoor plasma, cryoprecipitate, and fresh frozen
      plasma.
AB  - OBJECTIVE: To compare albumin concentrations, coagulation factors activity, and
      colloid osmotic pressure (COP) of cryoprecipitate (CRYO) and cryopoor plasma
      (CPP) to that of source fresh frozen plasma (FFP). DESIGN: Prospective in vitro
      study. SETTING: University teaching hospital. ANIMALS: Ten healthy, non-Greyhound
      dogs enrolled in an academic teaching hospital blood donor program.
      INTERVENTIONS: Fresh blood was obtained from canine blood donors and separated
      into FFP and packed red blood cells. The source FFP was further separated into
      CRYO and CPP. Albumin and fibrinogen concentrations, COP, activities of
      coagulation factors II, V, VII, VIII, IX, X, and von Willebrand factor (vWf) were
      assessed for each FFP, CRYO, and CPP. MEASUREMENTS AND MAIN RESULTS: The mean
      albumin concentration and COP in CPP were significantly higher compared with
      those found in FFP, with 31.7 g/L (+/-6) in CPP compared to 28.9 g/L (+/-0.5) in
      FFP (P < 0.001) and 14.5 mm Hg (+/-0.7) in CPP compared to 12.7 mm Hg (+/-0.3) in
      FFP (P = 0.03), respectively. CRYO had significantly higher concentrations of
      fibrinogen (median 3.46 g/L, 95% CI 2.65-4.27), and higher activities of factor
      VIII (mean activity 427.0%, +/-95.4) and vWf (mean activity 504.7%, +/-41.39) as
      compared to the other products. The activities of vitamin K dependent factors II,
      VII, and X were similar in CPP compared to FFP, although factor IX activity was
      lower in CPP. There was no significant difference in factor II or VII activities
      between the 3 products. CONCLUSIONS: The mean albumin concentration and COP were
      highest in CPP, suggesting that CPP may be a potential alternative to FFP for
      oncotic support and albumin replacement. CRYO contained higher activities of vWf
      and factor VIII than other products and could be used to treat vWf deficiency and
      hemophilia A. As vitamin K dependent coagulation factors II, VII, and X in CPP
      were similar to FFP, CPP may be an option for replacement of most of vitamin K
      dependent factors.

PMID- 29064154
TI  - Nanoscale Bubble Domains and Topological Transitions in Ultrathin Ferroelectric
      Films.
AB  - Observation of a new type of nanoscale ferroelectric domains, termed as "bubble
      domains"-laterally confined spheroids of sub-10 nm size with local dipoles self
      aligned in a direction opposite to the macroscopic polarization of a surrounding
      ferroelectric matrix-is reported. The bubble domains appear in ultrathin
      epitaxial PbZr0.2 Ti0.8 O3 /SrTiO3 /PbZr0.2 Ti0.8 O3 ferroelectric sandwich
      structures due to the interplay between charge and lattice degrees of freedom.
      The existence of the bubble domains is revealed by high-resolution piezoresponse
      force microscopy (PFM), and is corroborated by aberration-corrected atomic
      resolution scanning transmission electron microscopy mapping of the polarization
      displacements. An incommensurate phase and symmetry breaking is found within
      these domains resulting in local polarization rotation and hence impart a mixed
      Neel-Bloch-like character to the bubble domain walls. PFM hysteresis loops for
      the bubble domains reveal that they undergo an irreversible phase transition to
      cylindrical domains under the electric field, accompanied by a transient rise in
      the electromechanical response. The observations are in agreement with ab-initio
      based calculations, which reveal a very narrow window of electrical and elastic
      parameters that allow the existence of bubble domains. The findings highlight the
      richness of polar topologies possible in ultrathin ferroelectric structures and
      bring forward the prospect of emergent functionalities due to topological
      transitions.

PMID- 29064155
TI  - Assessing Inflammation in Acute Intracerebral Hemorrhage with PK11195 PET and
      Dynamic Contrast-Enhanced MRI.
AB  - BACKGROUND AND PURPOSE: Studies in animal models suggest that inflammation is a
      major contributor to secondary injury after intracerebral hemorrhage (ICH).
      Direct, noninvasive monitoring of inflammation in the human brain after ICH will
      facilitate early-phase development of anti-inflammatory treatments. We sought to
      investigate the feasibility of multimodality brain imaging in subacute ICH.
      METHODS: Acute ICH patients were recruited to undergo multiparametric MRI
      (including dynamic contrast-enhanced measurement of blood-brain barrier transfer
      constant (Ktrans ) and PET with [11 C]-(R)-PK11195). [11 C]-(R)-PK11195 binds to
      the translocator protein 18 kDa (TSPO), which is rapidly upregulated in activated
      microglia. Circulating inflammatory markers were measured at the time of PET.
      RESULTS: Five patients were recruited to this feasibility study with imaging
      between 5 and 16 days after onset. Etiologies included hypertension-related small
      vessel disease, cerebral amyloid angiopathy (CAA), cavernoma, and arteriovenous
      malformation (AVM). [11 C]-(R)-PK11195 binding was low in all hematomas and 2
      (patient 2 [probable CAA] and 4 [AVM]) cases showed widespread increase in
      binding in the perihematomal region versus contralateral. All had increased
      Ktrans in the perihematomal region (mean difference = 2.2 * 10-3 minute-1 ; SD =
      1.6 * 10-3 minute-1 ) versus contralateral. Two cases (patients 1 [cavernoma] and
      4 [AVM]) had delayed surgery (3 and 12 months post-onset, respectively) with
      biopsies showing intense microglial activation in perilesional tissue.
      CONCLUSIONS: Our study demonstrates for the first time the feasibility of
      performing complex multimodality brain imaging for noninvasive monitoring of
      neuroinflammation for this severe stroke subtype.

PMID- 29064156
TI  - Directed Evolution: Bringing New Chemistry to Life.
AB  - Tailor-made: Discussed herein is the ability to adapt biology's mechanisms for
      innovation and optimization to solving problems in chemistry and engineering. The
      evolution of nature's enzymes can lead to the discovery of new reactivity,
      transformations not known in biology, and reactivity inaccessible by small
      molecule catalysts.

PMID- 29064157
TI  - Inflammation and oxidative stress in corneal tissue in experimental keratitis due
      to Fusarium solani: Amelioration following topical therapy with voriconazole and
      epigallocatechin gallate.
AB  - Combined antifungal and antioxidant therapy may help to reduce oxidative stress
      in fungal keratitis. Experimental Fusarium solani keratitis was induced by
      application of F. solani conidia to scarified cornea (right eye) of 16 rabbits
      (another four rabbits were negative controls [Group I]). Five days later, F.
      solani-infected animals began receiving hourly topical saline alone (Group II),
      voriconazole (10 mg/mL) alone (Group III), epigallocatechin gallate (EGCG, 10
      mg/mL) alone (Group IV) or voriconazole and EGCG (Group V). Twenty days post
      inoculation, corneal lesions were graded. After animal sacrifice, excised corneas
      underwent histopathological and microbiological investigations. Corneal tissue
      levels/activities of interleukin 1 beta (IL-1beta) and tumour necrosis factor
      alpha (TNF-alpha) gene mRNA transcripts, matrix metalloproteinase (MMP) 2 and 9
      proteins, malondialdehyde (MDA) and reduced glutathione (GSH), and superoxide
      dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were also
      measured. Clinical and histopathological scores (severity of corneal lesions; [P
      < .05]) and mean levels (P < .05) of IL-1beta and TNF-alpha mRNA transcripts, MMP
      2, MMP 9 and MDA were Group II > Groups IV and III > Groups V and I. Mean SOD,
      CAT, GPx and GSH levels (P < .05) were Group II < Groups IV and III < Groups V
      and I. Topical voriconazole with EGCG apparently reduces inflammation in
      experimental F. solani keratitis, as manifested by improved clinical,
      histological, microbiological and molecular parameters.

PMID- 29064158
TI  - The natural compound 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d glucoside protects
      against adriamycin-induced nephropathy through activating the Nrf2-Keap1
      antioxidant pathway.
AB  - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-d-glucoside (THSG) is an active compound
      extracted from Polygonum multiflorum Thunb. This herb and radix Polygoni
      Multiflori preparata have been used to treat arteriosclerosis, hyperlipidemia,
      hypercholesterolemia, and diabetes for thousands of years. This study aimed to
      investigate the protective effects of THSG in an Adriamycin (AD)-induced focal
      segmental glomerulosclerosis (FSGS) mouse model and the underlying mechanisms in
      an in vitro system. Mice were treated with THSG (2.5 and 10 mg/kg, oral gavage)
      for 24 consecutive days. On the third day, mice were intravenously given a single
      dose of AD (10 mg/kg). At the end of the experiment, plasma and kidney samples
      were harvested to evaluate the therapeutic effects of THSG. The potential
      mechanisms of THSG in protecting against AD-induced cytotoxicity were examined
      using a real-time polymerase chain reaction, immunoblots, lactate dehydrogenase
      assay, and a cellular oxidized-thiol detection system in a mouse mesangial cell
      line. In this study, THSG showed concentration-dependent protective effects in
      ameliorating the progression of AD-induced FSGS. THSG suppressed albuminuria and
      hypercholesterolemia and reduced the status of lipid peroxidation in urine,
      plasma, and kidney tissue samples. Furthermore, THSG protected against podocyte
      damage, reduced renal fibrotic gene expressions, and alleviated the severity of
      glomerulosclerosis. Treatment of mouse mesangial cells with THSG induced nuclear
      factor erythroid-derived 2-like 2 (Nrf2) nuclear translocation, increased heme
      oxygenase-1 and NAD(P)H:quinone oxidoreductase (NQO)-1 gene expressions, and
      reduced cellular thiol oxidation and resistance to AD-induced cytotoxicity.
      Silencing Nrf2 and its repressor protein, Kelch-like ECH-associated protein 1
      (Keap1), abolished these protective effects of THSG. In conclusion, THSG can play
      a protective role in ameliorating the progression of FSGS in a mouse model
      through activation of the Nrf2-Keap1 antioxidant pathway. Although a well
      designed therapeutic study is needed, THSG may be applied to manage chronic
      kidney disease.

PMID- 29064159
TI  - Influence of catecholamines at different dosages on the function of the LiDCO
      sensor in isoflurane anesthetized horses.
AB  - OBJECTIVE: To compare the lithium dilution method for cardiac output (LiDCO) and
      bolus-thermo-dilution (BTD) measurements before and during infusion of
      dobutamine, dopamine, phenylephrine, or noradrenaline at 2 different doses in
      anesthetized horses and to examine the correlation between sensor voltages
      (saline-blood exposed) and possible measurement errors. DESIGN: Prospective
      experimental study. SETTING: University teaching hospital. ANIMALS: Nine
      Warmblood horses. INTERVENTIONS: Following 90 minutes of equilibration, 3
      different doses of dobutamine (0.5-3 MUg/kg/min), dopamine (1-5 MUg/kg/min),
      phenylephrine (0.5-3 MUg/kg/min), or noradrenaline (0.1-0.5 MUg/kg/min) were
      administered for 15 minutes in anesthetized horses, and measurements using the
      LiDCO were performed at the lowest and highest doses. Pairs of LiDCO and BTD
      measurements were collected and sensor voltages exposed to blood and saline were
      measured before and at the end of each infusion period. Agreement between LiDCO
      and BTD was assessed with the Bland-Altman method. MEASUREMENT AND MAIN RESULTS:
      The biases (2 standard deviations) before infusion of dobutamine, dopamine,
      phenylephrine, and noradrenaline were 1.1 (5.7), 1.6 (7.3), 0.2 (6.6), and 1.5
      (4.1) L/min, respectively, and minimally and nonsignificantly changed following
      low-dose catecholamine infusions. Following infusion of higher doses, biases were
      significantly higher compared to baseline with 10.7 (7.8), 11.2 (11.9), 6.9
      (11.7), and 3.5 (3.8) L/min, respectively. The difference between saline- and
      blood-exposed sensor voltage decreased during infusion of high doses of
      catecholamines with correlations (rs = 0.62) between cardiac output differences
      and sensor voltage differences (saline-blood). CONCLUSIONS: This study
      demonstrated that catecholamines could lead to overestimation in a dose-dependent
      fashion in LiDCO measurements. Monitoring changes in sensor voltage differences
      (saline-blood) is a valuable and clinically applicable tool to predict errors in
      LiDCO measurements.

PMID- 29064160
TI  - Marijuana commercialization and adolescent substance treatment outcomes in
      Colorado.
AB  - BACKGROUND AND OBJECTIVES: In Colorado, marijuana was legalized for medical use
      in 2000, commercialized in 2009, and approved for recreational purposes in 2012.
      Little is known about the association between recent policy changes and
      adolescent substance treatment outcomes measured by urine drug screens (UDS).
      This study addressed this research gap. METHODS: Participants were youth (N =
      523) aged 11-19 years who were enrolled in an outpatient motivational
      interviewing (MI)/cognitive behavioral therapy (CBT) plus contingency management
      (CM) in Denver, Colorado from October 2007 to June 2014. The measures included
      UDS collected during weekly treatment sessions and sent to a commercial
      laboratory for quantitative analysis of tetrahydrocannabinol (THC)/Creatinine
      (Cr). Linear regression models and logistic regression models using a Generalized
      Estimating Equations (GEE) approach for repeated measures were completed to
      answer the study aims. RESULTS: Males, but not females, had a marginally
      significant increasing trend over time in monthly average THC/Cr (beta = 1.99, p
      = 0.046). There was a significant increasing trend over time (per 30 days) in the
      odds of having a negative UDS within 6 sessions (OR = 1.02, 95%CI = 1.003-1.04, p
      = 0.006). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Based on these data, substance
      treatment outcomes from MI and CBT are mixed, but overall treatment appears to
      remain effective in a state with legalized marijuana. (Am J Addict 2017;26:802
      806).

PMID- 29064161
TI  - Immobilized optical fiber microprobe for selective and sensitive Escherichia coli
      detection.
AB  - Escherichia coli (E. coli) bacteria have been found to be responsible for various
      health outbreaks caused by contaminated food and water. Accurate and rapid test
      of E. coli is thus crucial for protecting the public health. A fast-response,
      label-free bacteriophage-based detection of E. coli using multimode microfiber
      probe is proposed and demonstrated in this paper. Due to the abrupt taper and
      subwavelength diameter, different modes are excited and guided in the microfiber
      as evanescent field that can interact with surrounding E. coli directly. The
      change of E. coli concentration and corresponding binding of E. coli bacteria on
      microfiber surface will lead to the shift of optical spectrum, which can be
      exploited for the application of biosensing. The proposed method is capable of
      reliable detection of E. coli concentration as low as 103 cfu/mL within the range
      of 103 to 107  cfu/mL. Owing to the advantages of high sensitivity and fast
      response, the microfiber probe has great potential application in the fields of
      environment monitoring and food safety.

PMID- 29064162
TI  - The novel allele, HLA-A*24:383, was identified in a Chinese individual by
      sequence-based typing.
AB  - HLA-A*24:383 differs HLA-A*24:02:01:01 by one nucleotide substitution from C to G
      in exon 4, position 755.

PMID- 29064163
TI  - The oxygen uptake efficiency slope is not a valid surrogate of aerobic fitness in
      cystic fibrosis.
AB  - BACKGROUND: Maximal cardiopulmonary exercise testing is recommended on an annual
      basis for children with cystic fibrosis (CF), due to clinically useful prognostic
      information provided by maximal oxygen uptake (VO2max ). However, not all
      patients are able, or willing, to reach VO2max , and therefore submaximal
      alternatives are required. This study explored the validity of the oxygen uptake
      efficiency slope (OUES) as a submaximal measure of VO2max in children and
      adolescents with CF. METHODS: Data were collated from 72 cardiopulmonary exercise
      tests (36 CF, 36 controls), with OUES determined relative to maximal and
      submaximal parameters of exercise intensity, time, and individual metabolic
      thresholds. Pearson's correlation coefficients, independent t-tests, and
      factorial ANOVAs were used to determine validity. RESULTS: Significant (P < 0.05)
      correlations with VO2max were observed for most expressions of OUES, but were
      consistently weaker in CF (r = 0.30-0.47) when compared to CON (r = 0.58-0.89).
      Mean differences for all OUES parameters between groups were not significant (P >
      0.05). When split by VO2max tertiles, minimal significant differences were found
      between, and within, groups for OUES, indicating poor discrimination of VO2max .
      CONCLUSIONS: The OUES is not a valid (sub) maximal measure of VO2max in children
      and adolescents with mild-to-moderate CF. Clinicians should continue to use
      maximal markers (ie, VO2max ) of exercise capacity.

PMID- 29064164
TI  - The aquaculture microbiome at the centre of business creation.

PMID- 29064165
TI  - Regarding "Lactation Status and Studies of Pyrimethamine Pharmacokinetics in
      Pregnancy".

PMID- 29064166
TI  - Non-invasive high-frequency oscillatory ventilation for preterm newborns: The
      time has come for consideration.

PMID- 29064167
TI  - Sequence-based typing identification of the novel HLA-C*07:565 variant in a
      Chinese family.
AB  - HLA-C*07:565 differs from HLA-C*07:02:01:01 (400C->T, exon 3, L110F).

PMID- 29064169
TI  - Unexpandable lung from pleural disease.
AB  - Unexpandable lung is a common complication of malignant pleural effusions and
      inflammatory pleural diseases, such as pleural infection (e.g. empyema and
      complicated parapneumonic effusion) and noninfectious fibrinous pleuritis.
      Unexpandable lung due to pleural disease may be because of an active pleural
      process, and is referred to as malignant or inflammatory lung entrapment. An
      unexpandable lung may also be encountered in the setting of remote pleural
      inflammation resulting in a mature fibrous membrane overlying the visceral pleura
      preventing full expansion of the lung. This condition is termed trapped lung and
      may be understood as a form of defective healing of the pleural space. Trapped
      lung typically presents as a chronic, stable pleural effusion without evidence of
      active pleural disease. An unexpandable lung most often manifests itself as an
      inability of fully expanding the lung with pleural space drainage. Patients will
      either develop chest pain preventing complete drainage of the pleural space or
      develop a post-procedure pneumothorax. Pleural manometry and radiological imaging
      are useful in the assessment of an unexpandable lung. Pleural manometry can
      demonstrate abnormal lung expansion during drainage and imaging will demonstrate
      abnormal visceral pleural thickening found in trapped lung or malignant and
      inflammatory lung entrapment.

PMID- 29064168
TI  - High prevalence of HIV and non-communicable disease (NCD) risk factors in rural
      KwaZulu-Natal, South Africa.
AB  - INTRODUCTION: South Africa faces epidemics of HIV and non-communicable diseases
      (NCDs). The aim of this study was to characterize the prevalence of non
      communicable disease risk factors and depression, stratified by HIV status, in a
      community with a high burden of HIV. METHODS: We conducted a home-based HIV
      counselling and testing study in KwaZulu-Natal, South Africa between November
      2011 and June 2012. Contiguous households were approached and all adults >=18
      years old were offered an HIV test. During follow-up visits in January 2015,
      screening for HIV, depression, obesity, blood glucose, cholesterol and blood
      pressure were conducted using point-of-care tests. RESULTS: Of the 570
      participants located and screened; 69% were female and 33% were HIV-positive. NCD
      risk factor prevalence was high in this sample; 71% were overweight (body mass
      index (BMI) 25 to 29.9 kg/m2 ) or obese (BMI>=30 kg/m2 ), 4% had hyperglycaemia
      (plasma glucose >11.0 mmol/l/200 mg/dl), 33% had hypertension (HTN, >140/90
      mmHg), 20% had hyperlipidaemia (low density cholesterol >5.2 mmol/l/193.6 mg/dl)
      and 12% had major depressive symptoms (nine item Patient Health Questionnaire
      >=10). Of the 570 participants, 87% had one or more of HIV, hyperglycaemia, HTN,
      hyperlipidaemia and/or depression. Over half (56%) had two or more. Older age and
      female gender were significantly associated with the prevalence of both HIV
      infection and NCD risk factors. Around 80% of both HIV-positive and negative
      persons had one of the measured risk factors (i.e. obesity, hyperglycaemia,
      hyperlipidaemia, HTN), or depression. CONCLUSIONS: In a community-based sample of
      adults in KwaZulu-Natal, South Africa, the prevalence of both HIV infection and
      NCD risk factors were high. This study is among the first to quantify the
      substantial burden of NCD risk factors and depression in this non-clinic based
      population.

PMID- 29064172
TI  - Measuring residual renal function for hemodialysis adequacy: Is there an easier
      option?
AB  - Most patients starting hemodialysis (HD) have residual renal function. As such,
      there has been increased interest in starting patients with less frequent and
      shorter dialysis session times. However, for this incremental approach to be
      successful, patients require regular monitoring of residual renal function, so
      that as residual renal function declines, the amount of HD is appropriately
      increased. Currently most dialysis centers rely on interdialytic urine
      collections. However, many patients find these inconvenient and there may be
      marked intrapatient variability due to compliance issues. Thus, alternative
      markers of residual renal function are required for routine clinical practice.
      Currently three middle sized molecules; cystatin C, beta2 microglobulin, and
      betatrace protein have been investigated as potential endogenous markers of
      glomerular filtration. Although none is ideal, combinations of these markers have
      been proposed to provide a more accurate estimation of glomerular clearance, and
      in particular cut offs for minimal residual renal function. However, in patients
      with low levels of residual renal function it remains unclear as to whether the
      benefits of residual renal function equally apply to glomerular filtration or
      tubular function.

PMID- 29064170
TI  - Sleep disordered breathing in bronchopulmonary dysplasia.
AB  - BACKGROUND: There are limited data on the effect of bronchopulmonary dysplasia
      (BPD) on sleep disordered breathing (SDB). We hypothesized that both the severity
      of prematurity and BPD would increase the likelihood of SDB in early childhood.
      Our secondary aim was to evaluate the association of demographic factors on the
      development of SDB. METHODS: This is a retrospective study of patient factors and
      overnight polysomnogram (PSG) data of children enrolled in our BPD registry
      between 2008 and 2015. Association between PSG results and studied variables was
      assessed using multiple linear regression analysis. RESULTS: One-hundred-forty
      children underwent at least one sleep study on room air. The mean respiratory
      disturbance index (RDI) was elevated at 9.9 events/hr (SD: 10.1). The mean
      obstructive apnea-hypopnea index (OAHI) was 6.5 (9.1) events/hr and the mean
      central event rate of 3.0 (3.7) events/hr. RDI had decreased by 22% or 1.5
      events/hour (95%CI: 0.6, 1.9) with each year of age (P = 0.005). Subjects with
      more severe respiratory disease had 38% more central events (P = 0.02). Infants
      exposed to secondhand smoke had 2.4% lower (P = 0.04) oxygen saturation nadirs
      and a pattern for more desaturation events. Non-white subjects were found to have
      33% higher OAHI (P = 0.05), while white subjects had a 61% higher rate of central
      events (P < 0.001). CONCLUSIONS: RDI was elevated in a selected BPD population
      compared to norms for non-preterm children. BPD severity, smoke exposure, and
      race may augment the severity of SDB. RDI improved with age but was still
      elevated by age 4, suggesting that this population is at risk for the sequelae of
      SDB.

PMID- 29064171
TI  - Breath detection by transcutaneous electromyography of the diaphragm and the
      Graseby capsule in preterm infants.
AB  - OBJECTIVE: To compare triggering, breath detection and delay time of the Graseby
      capsule (GC) and transcutaneous electromyography of the diaphragm (dEMG) in
      spontaneous breathing preterm infants. METHODS: In this observational study, a 30
      minutes respiration measurement was conducted by respiratory inductance
      plethysmography (RIP), the GC, and dEMG in stable preterm infants. Triggering was
      investigated with an in vitro set-up using the Infant Flow(r) SiPAPTM system. The
      possibility to optimize breath detection was tested by developing new algorithms
      with the abdominal RIP band (RIPAB ) as gold standard. In a subset of breaths,
      the delay time was calculated between the inspiratory onset in the RIPAB signal
      and in the GC and dEMG signal. RESULTS: Fifteen preterm infants with a mean
      gestational age of 28 +/- 2 weeks and a mean birth weight of 1086 +/- 317 g were
      included. In total, 14 773 breaths were analyzed. Based on the GC and dEMG
      signal, the Infant Flow(r) SiPAPTM system, respectively, triggered 67.8% and
      62.6% of the breaths. Breath detection was improved to 99.9% for the GC and
      113.4% for dEMG in new algorithms. In 1492 stable breaths, the median delay time
      of inspiratory onset detection was +154 ms (IQR +118 to +164) in the GC and -50
      ms (IQR -90 to -22) in the dEMG signal. CONCLUSION: Breath detection using the GC
      can be improved by optimizing the algorithm. Transcutaneous dEMG provides similar
      breath detection but with the advantage of detecting the onset of inspiration
      earlier than the GC.

PMID- 29064174
TI  - Preface.

PMID- 29064173
TI  - Evaluation of the functions of the temporary catheter with various tip types.
AB  - INTRODUCTION: A temporary catheter (TC) is used short-term and for emergencies.
      There are some cases when we cannot withdraw blood immediately after inserting
      the catheter in our patients. The reason is said to be the tips of the TC
      sticking to the vascular walls. OBJECTIVE: We evaluated examined 3 catheters with
      different tip shapes in a simulation circuit to assess the effect on the blood
      flow. METHODS: Water was circulated in the simulation circuit at 1 L/minute.
      Next, we inserted each TC into the model, and the TCs were connected to the
      dialysis circuit at 200 mL/minute. We put gold powder into the simulation
      circuit. We visually observed the movement of the gold power at the head of the
      catheter and measured the recirculation rate. RESULT: The uplift type TC was able
      to perform blood removal and reinfusion with the least difficulties. All
      recirculation rates were less than 1%. The hindrance caused by hitting a vascular
      wall is believed to have been reduced. CONCLUSION: With the manipulation of the
      catheter tip shapes, blood was able to circulate smoothly. We expect less blood
      clots and a decrease in sticking to the vascular wall. We plan to study these 3
      catheters at clinical tests in the future.

PMID- 29064175
TI  - Verification of physicochemical structures of dialysis membrane using reversal
      dialysis technique.
AB  - OBJECTIVE: Solute removal performance of the dialyzer is closely related to
      physicochemical structures of the membrane. The objective of this study is to
      devise a new in vitro evaluation technique to directly correlate the
      physicochemical structures of the membrane to the dialysis performance. MATERIALS
      AND METHODS: Commercial 11 dialyzers with cellulose triacetate (CTA), ethylene
      vinylalcohol co-polymer (EVAL), asymmetry CTA (termed ATA), 4 polysulfone (PSf),
      polyether sulfone (PES), and 3 polyester polymer alloy (PEPA) membranes were
      employed for investigation. Normal dialysis experiments were performed with
      aqueous creatinine (MW 113), bromophenol blue (MW 670), vitamin B12 (MW 1355),
      chymotrypsin (MW 25,000) test solutions. Reversal dialysis experiments were
      devised introducing the test solution outside the hollow fiber (HF) and the
      dialysate inside the HF, respectively. Clearances were measured under QB  = 200
      mL/min and QD  = 500 mL/min at 310 K. The ratio of clearance in the reversal
      dialysis to that in the normal dialysis termed the yielding factor of asymmetry,
      fYA , was defined for evaluation. RESULTS AND DISCUSSION: According to the
      classic mass transfer theory, clearance in the normal dialysis and that in the
      reversal dialysis are expected to be identical; however, the average fYA was 0.96
      for creatinine and was always slightly lower than unity in 10 dialyzers out of
      11. This may be caused by un-uniform distribution of the test solution outside
      the HF, which was more likely to occur than when it flowed inside the HF. Unlike
      creatinine, the average fYA for vitamin B12 was 1.0 and that for chymotrypsin was
      1.06 to 1.45 in membranes with heterogeneous structures (ATA, PSf, PEPA, and
      PES), but was almost unity (1.02) in homogeneous membrane (CTA). This must be
      based on the fact that the membrane permeability in the reversal dialysis is much
      larger than that in the normal dialysis due to the physicochemical structures of
      the heterogeneous membrane that has a wedge-like pore size distribution in the
      radial direction. CONCLUSIONS: A wedge-like pore size distribution in the radial
      direction in heterogeneous membrane was semiquantitatively evaluated by
      introducing a reversal dialysis technique with a new index.

PMID- 29064176
TI  - Calciphylaxis after parathyroidectomy.
AB  - A 60-year-old African American man with end stage renal disease on hemodialysis
      (HD) for the past 2.5 years developed severe hyperparathyroidism. Other past
      medical history included atrial fibrillation, type II diabetes mellitus,
      hypertension, gout, pericardial effusion needing pericardial window, deep vein
      thrombosis, mitral insufficiency, and cardiomyopathy with implantable
      cardioversion device placement. His parathyroid hormone (PTH) level peaked at
      4,191 pg/mL despite being on cinacalcet, sevelamer, and paricalcitol. He
      underwent a subtotal parathyroidectomy in January 2015, after which his PTH
      levels dropped to 184 pg/mL. Approximately 4 weeks later he developed extensive,
      painful necrotic skin lesions in both his lower extremities and buttocks,
      suggestive of calciphylaxis which was confirmed by tissue biopsy. The patient was
      treated with elaborate wound care, wound debridements, increased dialysis dose,
      and IV sodium thiosulfate (STS) during hemodialysis. Besides STS, he was treated
      with narcotics, gabapentin, topical lidocaine on intact skin, and oral steroids
      for pain control. Even though his lesions improved initially, he deteriorated due
      to recurrent sepsis, respiratory failure, and prolonged hospitalization which
      culminated in stopping dialysis before he passed away. Calciphylaxis, or calcific
      uremic arteriolopathy, is a life-threatening complication of end stage renal
      disease. Treatment of this condition is multidisciplinary which includes
      elaborate wound care, increasing dialysis dose, and discontinuing vitamin D
      supplements and calcium containing phosphate binders. Even though STS has been
      recommended off-label, several studies have shown promising results with
      resolution of lesions. Thus, sodium thiosulfate has become the mainstay of
      treatment. Parathyroidectomy is a recommended modality of treatment in those with
      high PTH levels. Our case was unique in that calciphylaxis developed after
      subtotal parathyroidectomy. We believe that this is due to a decreased PTH level
      and decreasing bone turnover which resulted in more circulating calcium
      facilitating vascular and soft tissue calcification. The exact mechanism of
      developing calciphylaxis after parathyroidectomy is unknown. Even though
      parathyroidectomy is an effective treatment for calciphylaxis, clinicians should
      be aware that it can rarely present after parathyroidectomy.

PMID- 29064177
TI  - MicroRNA 499 gene expression in patients on hemodialysis with cardiovascular
      complications.
AB  - BACKGROUND: MicroRNA (miRNA) 499 is an evolutionarily conserved muscle-specific
      miRNA that is encoded by an intron of the myh7 gene and is likely to play a role
      in myosin gene regulation. It has been shown to be involved in inhibiting
      apoptosis and myocardial infarction induced by ischemia and anoxia. It is unknown
      whether levels of miRNAs are affected in patients undergoing hemodialysis.
      OBJECTIVE: The aim of this study was to assess circulating levels of miRNA 499 in
      hemodialysis patients and whether the levels are affected by dialyzer membranes
      (high flux vs. low flux). METHODS: The studied population consisted of 32 end
      stage renal disease (ESRD) patients (22 males and 10 females) with age ranged
      from 38% to 75% years on regular hemodialysis (4 hours, 3 times weekly) for at
      least 1 year duration with cardiovascular events in the last 6 months and 32
      healthy controls (20 males and 12 females) with an age range from 54 to 60 years.
      Patients were involved into a two-stage sequential study; high-flux hemodialysis
      stage (stage I), then low-flux hemodialysis stage (stage II). Expressed levels of
      plasma miRNA 499 have been measured by Real Time-PCR. Lipid profile, serum
      phosphorus, serum calcium, serum creatinine, and blood urea were measured in all
      patients. RESULTS: In this study, 2 patients with an open-heart surgery showed
      highly elevation in the miRNA 499, while the other patients, showing different
      degrees of ischemia, had different levels of elevated miRNA 499. Statistically
      significant higher levels of miRNA 499 in plasma were observed in all the studied
      patients with cardiovascular diseases compared to the levels of miRNA 499 found
      in healthy controls (P < 0.0001). MicroRNA 499 was found to be a dialyzable
      marker. A significant decrease in plasma levels of miRNA 499 was obtained after
      either high-flux or low-flux dialysis compared to plasma levels of miRNA 499
      found before dialysis (P < 0.0001). On comparing both types of hemodialysis
      membranes with respect to miRNA 499 clearance, we found that low-flux membrane
      showed better clearance for miRNA 499 than high-flux membrane with a
      statistically significant difference between them (P < 0.001). CONCLUSION: In
      conclusion, miRNA 499 levels are elevated in patients with ESRD with
      cardiovascular complications. High-flux membrane seems to be less efficient in
      miRNA 499 clearance in cardiac patients on hemodialysis.

PMID- 29064178
TI  - Low dialysate potassium concentration is associated with prolonged recovery time.
AB  - INTRODUCTION: Modifiable hemodialysis treatment parameters may impact patient
      reported outcomes, including recovery time. Answers to the recovery question may
      predict the impact of treatment parameters on clinical outcomes and health
      related quality of life. However, the reliability of answers to the recovery
      question after consecutive and nonconsecutive dialysis treatments in diverse
      populations has not been established. OBJECTIVE: To assess the reliability of
      this instrument and to determine if recovery time was associated with modifiable
      dialysis parameters, we conducted a quality assurance project in which we asked,
      "How long did it take you to recover from your last dialysis session?" after
      consecutive and nonconsecutive treatments. METHODS: We asked patients the
      recovery question <= seven times. We computed polychoric correlations to assess
      within patient correlations. We used random intercept ordinal logistic regression
      models to test for associations of recovery time with patient variables. RESULTS:
      We obtained answers to the recovery question in association with 1572 treatments
      in 364 patients. Recovery time was <2 hours in 52.1%; 2 to 7 hours in 20.9%; and
      >7 hours in 27.0% of treatments. Polychoric correlations demonstrated highly
      reliable responses within individual patients between consecutive and
      nonconsecutive treatments. Prolonged recovery was associated with a dialysate
      potassium of 1 vs. 2 mEq/L (odds ratio [OR] 2.25 {95% confidence interval [CI]
      1.43-3.55}) and 1 vs. 3 mEq/L (OR 1.88 [95% CI 1.06-3.33]); vintage >6 months (OR
      2.43 [95% CI 1.42-4.16]), body mass index >35 kg/m2 (OR 1.94 [95% CI 1.18-3.20]),
      post-dialysis systolic blood pressure (SBP) <115 mmHg (OR 1.57 [95% CI 1.04
      2.37]) and intradialytic cramps (OR 1.76 [95% CI 1.09-2.86]). There were no
      associations with gender, race, age, ESRD etiology, intradialytic SBP <90 mmHg,
      serum sodium or potassium, dialysate sodium, bicarbonate or temperature, blood
      flow rate, or ultrafiltration rate. CONCLUSIONS: Responses to the recovery
      question were reliable and low dialysate potassium was associated with prolonged
      recovery.

PMID- 29064179
TI  - A case of hypothermia on CRRT.
AB  - A 64-year-old Asian man, with past medical history of hypertension,
      hypothyroidism, and hyperlipidemia, presented with 3 days history of fever
      associated with cough and worsening shortness of breath. Subsequent clinical
      course was complicated by acute lung injury leading to acute respiratory distress
      syndrome requiring positive pressure ventilation, septic shock requiring
      inotropic support, and acute kidney injury requiring continuous renal replacement
      therapy (CRRT). On day 3 of CRRT, the patient developed significant hypothermia
      (temporal temperature 27.5 degrees C), which was successfully managed. Continuous
      renal replacement therapy was subsequently discontinued as renal function
      recovered and the patient was discharged home after a prolonged hospital stay. He
      currently remains off dialysis and is being followed as an outpatient for chronic
      kidney disease. In this article, we examine various aspects of pathophysiology
      and management of hypothermia on CRRT and review relevant literature in this
      field.

PMID- 29064180
TI  - A service review to assess if innovative intensive phosphate dietary education
      can help reduce phosphate levels to the recommended range in a hemodialysis
      population.
AB  - INTRODUCTION: Studies suggest that hemodialysis (HD) patients are less likely to
      adhere to phosphate dietary restriction than to potassium, sodium, or fluid
      restriction. It is particularly important that dietary education is provided
      appropriately, consistently, and reinforced regularly to encourage compliance
      with diet and phosphate-binder regimens. Patient awareness of the consequences of
      a chronically raised phosphate and its treatment is associated with lower serum
      phosphate levels. OBJECTIVE: The aim of this study was to assess the impact of a
      structured educational program on patient knowledge and control of serum
      phosphate in a maintenance HD population. METHODS: Thirty-six patients with a
      phosphate level >1.7 mmol/L for the previous 3 months were assessed. A phosphate
      knowledge questionnaire was devised by the authors and completed by the patient
      group. This focused on patient knowledge of dietary sources of phosphate and
      complications of high phosphate levels. The education program was divided into
      three modules and was based around diet, phosphate additives, and complications
      of hyperphosphatemia. Visual aids, oral, and written information were provided to
      each patient throughout the sessions. Seventeen patients completed the education
      sessions. The knowledge and food frequency questionnaire were repeated at the end
      of the modules to assess change. RESULTS: Phosphate levels dropped from an
      average of 2.12-1.73 mmol/L over the education period with a significance level
      of P = 0.000481 (significant if P < 0.001). This average falls in line with
      recommended guidelines. Knowledge questionnaire results improved overall.
      CONCLUSION: This education program displayed excellent outcomes with an overall
      reduction in phosphate levels and an improved phosphate knowledge among our
      sampled HD population. This education program shows that discovering novel ways
      of education is crucial to enhancing dietetic practice with renal dietitians best
      placed to deliver patient specific phosphate education.

PMID- 29064181
TI  - A Mayo Clinic 13-year investigation of the syndrome of rapid onset ESRD among
      renal transplant recipients: An analysis of the implications of renal allograft
      biopsy results.
AB  - INTRODUCTION: We first described the syndrome of rapid onset end stage renal
      disease (SORO-ESRD), acute yet irreversible renal failure, in 2010. OBJECTIVE:
      The impact of SORO-ESRD renal allograft survival remains speculative and we plan
      to study this question. METHODS: A retrospective analysis of individual adult
      patient-level serum creatinine trajectories of ESRD patients on maintenance
      hemodialysis for >90 days at Mayo Clinic, Rochester, 2001-2013. RESULTS: Of 1461
      ESRD patients, 149 (10%) patients including 13 renal transplant recipients (RTRs)
      satisfied the diagnosis of SORO-ESRD - 4 males, 9 females, 12 Caucasians/one
      other, age 45 (18-83) years. Serum creatinine was 1.4 (0.8-1.7) mg/dL in the last
      year before hemodialysis initiation. Initial hemodialysis access was a dialysis
      catheter in all 13 patients. AKI precipitating SORO-ESRD followed acute rejection
      (4), postoperative (2), tubulo-interstitial nephritis (2), unknown (2),
      infection/sepsis (1), contrast nephropathy (1), BKV nephropathy (1), and cardio
      renal syndrome (1). Renal allograft survival was 1469 (277-4939) days (4 years).
      Renal allograft biopsies were available in 9/14 (69%) RTRs - Four showed acute
      rejection, two of which followed interruption of immunosuppression, three
      revealed acute tubular necrosis and four others also showed chronic transplant
      glomerulopathy. Time on hemodialysis was 856 (129-1630) days (2.4 years). 5/13
      RTRs with SORO-ESRD (38%) died - 3 (60%) following cardiac arrest, 2 (40%) after
      stopping hemodialysis. 4/13 (31%) were re-transplanted in the period of this
      study. CONCLUSION: SORO-ESRD contributed significantly to late renal allograft
      loss and return to hemodialysis with 100% initial dialysis catheter rate.
      Potentially preventable causes of AKI leading to SORO-ESRD were identified. The
      application of experience gained from such studies would help reduce late renal
      allograft loss and the need for re-transplantation. This would further help
      reduce the yawning gap between need and availability of donor kidney organs both
      here in the United States and around the world. Larger studies are warranted.

PMID- 29064182
TI  - Anti-thrombotic therapy for atrial fibrillation in patients with chronic kidney
      disease: Current views.
AB  - Chronic kidney disease (CKD) occurs in approximately one-third of patients with
      non-valvular atrial fibrillation (AF). The presence of CKD, particularly advanced
      CKD, confers increased risk of both thromboembolism and major bleeding in this
      group of patients who are already at risk for ischemic stroke and systemic
      embolism and at risk of bleeding due to anticoagulation. Studies assessing the
      effect of warfarin on risk of ischemic stroke, systemic embolism, and major
      bleeding have produced disparate results, particularly in patients with advanced
      CKD including those treated with hemodialysis. The direct oral anticoagulants
      (DOAC's) have been studied in patients with stage III (moderate) CKD and appear
      to be as effective or more effective (dabigatran 150 mg twice daily) than
      warfarin in preventing ischemic stroke or embolism in this group. Two of the
      DOAC's, apixaban and edoxaban, confer lower risk of major bleeding than warfarin
      with appropriate dose adjustments. Substantial gaps exist in our knowledge of
      anti-thrombotic therapy in patients with AF and CKD, primarily due to exclusion
      of patients with advanced CKD from randomized controlled trials comparing DOAC's
      with warfarin.

PMID- 29064183
TI  - Induced sputum versus broncho-alveolar lavage for pathogen surveillance in young
      cystic fibrosis patients: Low specificity is not necessarily a bad thing.

PMID- 29064185
TI  - Field efficacy of insect pathogen, botanical, and jasmonic acid for the
      management of wheat midge Sitodiplosis mosellana and the impact on adult
      parasitoid Macroglenes penetrans populations in spring wheat.
AB  - The wheat midge, Sitodiplosis mosellana, is a serious pest of wheat worldwide. In
      North America, management of S. mosellana in spring wheat relies on the timely
      application of pesticides, based on midge adults levels caught in pheromone traps
      or seen via field scouting during wheat heading. In this context, biopesticides
      can be an effective alternative to pesticides for controlling S. mosellana within
      an Integrated Pest Management program. A field study using insect pathogenic
      fungus Beauveria bassiana GHA, nematode Steinernema feltiae with Barricade
      polymer gel 1%, pyrethrin, combined formulations of B. bassiana GHA and
      pyrethrin, Jasmonic acid (JA) and chlorpyrifos (chemical check) was performed to
      determine to which extent they affect midge larval populations, kernel damage
      levels, grain yield, and quality, and the impacts on adult parasitoid Macroglenes
      penetrans populations. The results indicated that biopesticides JA and S. feltiae
      were the most effective in reducing larval populations and kernel damage levels,
      and produced a higher spring wheat yield when compared to the water control at
      both study locations (East Valier and North Valier, Montana, USA). Increased test
      weight in wheat had been recorded with two previous biopesticides at East Valier
      but not for North Valier, when compared over water control. These results were
      comparable in efficacy to the chlorpyrifos. This study also suggested that B.
      bassiana and pyrethrin may work synergistically, as exemplified by lower total
      larval populations and kernel damage levels when applied together. This study did
      not demonstrate the effect of any treatments on M. penetrans populations.

PMID- 29064184
TI  - Cystic fibrosis clinical characteristics associated with dornase alfa treatment
      regimen change.
AB  - BACKGROUND: When the chronic respiratory therapy dornase alfa was made
      commercially available for cystic fibrosis (CF) more than 20 years ago, two
      regimens were approved: 2.5 mg inhaled once daily (QD) or twice daily (BID). In
      the intervening years, there has been little guidance as to when to use each
      regimen. We have studied clinical practice patterns captured in the Epidemiologic
      Study of CF (ESCF) during the decade following dornase alfa approval (1994-2005)
      to better understand clinical characteristics associated with QD versus BID
      dornase alfa use. Methods We studied the characteristics of ESCF patients who
      received either dornase alfa regimen for at least 12 months and who were then
      switched to the alternate regimen for at least 6 months and who had adequate data
      available around the time of the switch. Average lung function and weight-for-age
      (WFA) z-scores, numbers of intravenous (IV) antibiotic-treated pulmonary
      exacerbations, and prevalence of signs and symptoms were determined for 6-month
      periods capturing the beginning (FIRST) and the end (LAST) of the initial
      regimen, the 6 months preceding the final 6 months of the initial regimen
      (PRIOR), and the beginning of the second regimen (POST). Changes in values from
      FIRST to LAST, PRIOR to LAST, and LAST to POST were studied to better understand
      clinical scenarios associated with decisions to change regimens. RESULTS: A total
      of 1342 QD and 574 BID regimens were studied with median durations of 3.19 and
      2.09 years, respectively. On average, patients beginning BID regimens had worse
      lung function and a greater number of pulmonary exacerbations treated with IV
      antibiotics than those beginning QD regimens. However, by the time of regimen
      switch, patients switching from QD to BID dornase alfa had experienced
      substantial deterioration with respect to pulmonary exacerbations and signs and
      symptoms, whereas patients switching from BID to QD had not. Interestingly,
      incidence of IV-treated pulmonary exacerbations and signs and symptom prevalence
      decreased for both populations after regimen switch. CONCLUSIONS: We have studied
      populations of patients with CF receiving dornase alfa who were switched between
      regimens to characterize clinical course. Our results suggest that the most
      common clinical attribute associated with switching from QD to BID dornase alfa
      was a marked deterioration in stability characterized by increased incidence and
      frequency of pulmonary exacerbation. For this population, deterioration in lung
      function did not appear to be a driver for this switch. In contrast, patients
      receiving BID dornase alfa who were ultimately switched to QD appeared to be
      clinically stable, on average, suggesting that treatment burden and cost may have
      been drivers of the decision to switch regimens.

PMID- 29064186
TI  - Weaning long term non-invasive ventilation (NIV) therapy in children.

PMID- 29064187
TI  - Posterior corneal surface differences between non-laser in situ keratomileusis
      (LASIK) and 10-year post-LASIK myopic eyes.
AB  - PURPOSE: To evaluate the posterior corneal surface differences between non-laser
      in situ keratomileusis (LASIK) and 10-year post-LASIK myopic eyes. METHODS: The
      study included 130 eyes from 65 patients, who were treated with myopic LASIK 10
      years ago. In addition, 130 eyes from 65 unoperated myopic patients of matching
      present age and preoperative refraction were divided into control group. Data on
      the posterior corneal surface and anterior chamber were obtained from Pentacam
      software and compared between the groups. Postoperative visual acuity (VA) and
      refractive error were also analysed. RESULTS: The mean preoperative spherical
      equivalent (SE) was -6.99 +/- 1.78 dioptre (D) in the LASIK group. Ten years
      after surgery, the mean SE was -0.45 +/- 1.22 D, the efficacy index was 0.98, and
      the safety index was 1.01. The posterior corneal elevations of the LASIK group at
      2 mm corneal diameter were significantly lower than those of the control group.
      However, posterior corneal elevations at 6 mm corneal diameter were higher in the
      LASIK group than the controls (p < 0.01 for all). The mean Q-values of posterior
      corneal surface demonstrated significant positive direction compared to that of
      control eyes at 6 and 7 mm corneal diameters (p < 0.05 for both). At the thinnest
      point of the cornea, the anterior chamber depths were shallower in the LASIK
      group than in controls. Meanwhile, the anterior chamber volumes (ACV) were
      smaller in the LASIK group than in the control group. CONCLUSION: Our results
      demonstrated that the posterior corneal surface tends to show signs of central
      flattening and peripheral steepening 10 years after myopic LASIK surgery compared
      to that of non-operated myopic eyes.

PMID- 29064188
TI  - Reconsidering Water Electrolysis: Producing Hydrogen at Cathodes Together with
      Selective Oxidation of n-Butylamine at Anodes.
AB  - Electrocatalysis for the oxygen evolution reaction (OER) is of great interest for
      improving the effectiveness of water splitting devices. Decreasing the anodic
      overpotential and simultaneously changing the anodic reaction selectively to
      produce valuable chemicals instead of O2 would be a major improvement of the
      overall cost efficiency. Some amines, when present in aqueous electrolytes, were
      recently shown to change the selectivity of the anodic process to generate H2 O2
      rather than O2 on MnOx at pH 10. This results in unusually high apparent "anodic
      activities". In this work, industrially relevant OER catalysts, oxyhydroxides of
      cobalt (CoOx ), nickel-iron (NiFeOx ), and nickel (NiOx ) all show more
      pronounced effects. Moreover, as anodes they also selectively catalyzed the
      production of nbutyronitrile from n-butylamine at higher pH as an easily
      retrievable valuable product. The pH dependence of the activity was investigated
      at pH values closer those at which alkaline electrolyzers operate. The highest
      activities were observed for NiOx thin-film electrodes at pH 12 in the presence
      of 0.4 m n-butylammonium sulfate, without poisoning the active sites of Pt
      electrocatalysts at the hydrogen evolution electrode. 1 H NMR spectroscopy showed
      that n-butylamine is selectively oxidized to n-butyronitrile, an organic chemical
      with numerous applications. However, measurements using rotating ring-disk
      electrodes indicated that some H2 O2 is also generated at the surface of the
      oxide anodes.

PMID- 29064189
TI  - Three new HLA class I alleles with synonymous mutations: HLA-A*03:01:62, 
      C*07:02:82 and -C*12:03:42.
AB  - Three new HLA class I alleles with synonymous mutations were identified.

PMID- 29064190
TI  - Portable optical-resolution photoacoustic microscopy for volumetric imaging of
      multiscale organisms.
AB  - Photoacoustic microscopy (PAM) provides a fundamentally new tool for a broad
      range of studies of biological structures and functions. However, the use of PAM
      has been largely limited to small vertebrates due to the large size/weight and
      the inconvenience of the equipment. Here, we describe a portable optical
      resolution photoacoustic microscopy (pORPAM) system for 3-dimensional (3D)
      imaging of small-to-large rodents and humans with a high spatiotemporal
      resolution and a large field of view. We show extensive applications of pORPAM to
      multiscale animals including mice and rabbits. In addition, we image the 3D
      vascular networks of human lips, and demonstrate the feasibility of pORPAM to
      observe the recovery process of oral ulcer and cancer-associated capillary loops
      in human oral cavities. This technology is promising for broad biomedical studies
      from fundamental biology to clinical diseases.

PMID- 29064191
TI  - ?

PMID- 29064192
TI  - [Detection of bacteriemia by blood cultures : who will benefit ?]
AB  - Blood cultures are often prescribed in the hospital setting, even if their yield
      is weak. It's important to try to predict which patient will really benefit from
      them. There are some parameters that increase the chances of positivity of a
      blood culture, such as septic choc, chills or suspicion of Staphylococcus aureus
      bacteremia. Fever is not indicative. There are some clinical scores that permit
      to determinate the probability of a blood culture's positivity ; they haven't a
      high specificity, thus allowing mainly to avoid the taking of blood cultures
      whose risk of being negative is high. A new subject of interest in the field of
      infectious disease is the prediction of a resistant-organism bacteremia. This
      article aims to summarize the main predictions that we can draw when it comes to
      evaluate the utility of collecting a blood culture.

PMID- 29064194
TI  - [Proton pump inhibitors overprescription].
AB  - Overutilization of proton pump inhibitors (PPI) is obvious despite available
      recommendations, with clinical and economical issues. This overuse is due to
      abusive stress ulcer prophylaxis and to automatic represcription, particularly
      during transitions from intensive care unit to other inhospital units and at
      hospital discharge. Withdrawal symptoms may contribute to the difficulty of PPI
      interruption. It is mandatory to limit initiation of PPI treatment outside of
      appropriate indications and to regularly reassess the need of this treatment.

PMID- 29064193
TI  - [Paracentesis and cirrhotic patients: should we fear hemorrhages ?]
AB  - Paracentesis is a frequent procedure, especially in patients with cirrhosis. In
      these patients, given the fears of severe bleeding associated with coagulation
      disorders as well as thrombocytopenia, we were interested to review the
      literature on this subject. Few studies are available and, for the moment,
      recommendations are of a low level of evidence. Paracentesis seems to be a safe
      procedure without severe haemorrhagic complications (< 1%), regardless of
      coagulation disorders and platelet count. Renal insufficiency, Child-Pugh C
      cirrhosis, thrombocytes < 50 G/L and cirrhosis of alcoholic origin may however
      increase the risk of bleeding. Caution should be observed in these patients.

PMID- 29064195
TI  - [Prevention of thrombosis among medical inpatients : should we adapt enoxaparin
      doses to the patient's weight ?]
AB  - Venous thromboembolism (VTE) is a common condition affecting hospitalized
      patients and it is associated with increased mortality, length of stay and health
      care costs. Prophylaxis using low-molecular weight heparins (LMWH) is an
      efficient intervention preventing VTE in high-risk patients, yet some evidence
      suggests suboptimal prophylaxis in obese inpatients. This narrative review
      evaluates current evidence, both on clinical and surrogate outcomes, which can
      guide the adaptation of prophylactic doses of enoxaparin among obese medical
      inpatients.

PMID- 29064196
TI  - [A palliative care approach of patients with chronic obstructive pulmonary
      disease].
AB  - Chronic obstructive pulmonary disease (COPD) is a frequent, progressive and
      lethal disease. As opposed to other chronic illnesses, such as cardio-vascular
      diseases, the prevalence of COPD is still on the rise. It is now well documented
      that these patients can present many invalidating symptoms towards the end of
      their life. The aim of a palliative approach for patients living with advanced
      COPD is to decrease the impact of symptoms and offer a pluridisciplinary approach
      so as to maintain the best possible quality of life.

PMID- 29064197
TI  - [Reactive hemophagocytic syndrome].
AB  - The reactive hemophagocytic syndrome comes from an overstimulation of the immune
      system which causes a cytokine storm. This is a life-threatening condition
      caracterised by a febrile cytopenia, hepatosplenomegaly and multi-organ failure.
      The diagnosis is not easy and the HScore can be useful, looking at
      hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. The evidence of
      hemophagocytosis in the bone marrow is not necessary nor sufficient to make the
      diagnosis but is part of the workup. The underlying cause has to be actively
      sought, typically an infectious, malignant or autoimmune disorder. This syndrome
      should be supported in conjunction with the hematologist, and initiation of a
      treatment is a medical emergency.

PMID- 29064199
TI  - ?

PMID- 29064198
TI  - [Revised WHO classification 2016 of gliomas : what's new ?]
AB  - The revised WHO classification 2016 of central nervous system tumours
      incorporates molecular biomarkers in addition to histological features in an "
      integrated diagnosis ". Thus, it refines classification with more homogenous
      diagnosis groups in order to improve prognosis and to guide treatment, notably
      for gliomas. This article firstly summarized the new concept of this revised
      classification, some basis of the molecular genetics of gliomas and practical
      application of the " integrated diagnosis ". It analyses the impact of this
      classification on the diagnosis and outcome of gliomas performed at the
      University Institute of Pathology - CHUV, Lausanne from October 2015 to November
      2016.

PMID- 29064200
TI  - ?

PMID- 29064202
TI  - ?

PMID- 29064201
TI  - ?

PMID- 29064203
TI  - ?

PMID- 29064204
TI  - ?

PMID- 29064205
TI  - The association between serum vitamin D levels and urticaria: a meta-analysis of
      observational studies.
AB  - INTRODUCTION: Despite the recent studies revealed Vitamin D may play a role in
      urticaria, no meta-analysis providing definite conclusions in this field has been
      reported. EVIDENCE ACQUISITION: A systematic search up to June 30th, 2017 was
      conducted in MEDLINE (via PubMed) and Excerpta Medica database (EMBASE) to
      identify relevant articles. Search terms included ''vitamin D'' or "25
      hydroxyvitamin D" or "25-hydroxy-vitamin D" or "25(OH)D" or "1,25
      dihydroxyvitamin D" combined with ''urticaria." EVIDENCE SYNTHESIS: Initial
      searches yielded 30 citations. Of these original results, 10 met specific
      selection criteria and were included in the meta-analysis with 547 urticaria
      cases and 517 controls. Vitamin D levels were significantly decreased in the
      urticarial cases (WMD -9.8 mg/L, 95% CI: -12.57 to -7.04 mg/L, from a random
      effects model), with a significant heterogeneity (I2=85.9%, P=0.000). When divide
      the Vitamin D level into two subgroups, the pooled OR comparing vitamin D
      insufficiency vs. normal level was 1.64 (95% CI: 0.71 to 3.77). Meanwhile,
      vitamin D deficiency vs. normal level was 4.09 (95% CI: 1.32 to 12.73).
      CONCLUSIONS: The study demonstrated that patients with urticaria had a lower
      Vitamin D level than healthy controls. Vitamin D deficiency rather than
      insufficiency has a positive relationship with urticaria. However, larger-scale
      studies with a longer duration of treatment are needed to confirm this
      conclusion.

PMID- 29064206
TI  - Correlation of changes in HIF-1alpha and p53 expressions with vitamin B3
      deficiency in skin cancer patients.
AB  - BACKGROUND: To investigate the correlation of changes in hypoxia-inducible factor
      1alpha (HIF-1alpha) and p53 expressions with vitamin B3 deficiency in skin cancer
      patients. METHODS: Twenty non-melanoma skin cancer patients with positive HIF
      1alpha and p53 expressions were selected and randomly divided into two groups,
      the placebo group and the experimental group. After an appropriate number of
      cancer tissues were taken, the experimental group was treated with oral
      administration of 500 mg vitamin B3 every day, while the placebo group was
      treated with oral administration of the same amount of placebo; after 1 week, the
      skin cancer tissues in the same part were taken, and the skin tissues of healthy
      people were taken as the control group; the mRNA and protein expression levels of
      HIF-1alpha and p53 in tissues were detected. RESULTS: HIF-1alpha and p53 were
      mainly expressed in the nucleus in non-melanoma skin cancer. The protein and mRNA
      expression levels of HIF-1alpha and p53 in tissues of skin cancer patients were
      significantly increased compared with those in skin tissues of healthy people
      (p<0.05). The protein and mRNA expression levels of HIF-1alpha and p53 in tissues
      of skin cancer patients were significantly decreased at 1 week after the oral
      administration of vitamin B3 compared with those before the oral administration
      of vitamin B3 (p<0.05), but the protein and mRNA expression levels of HIF-1alpha
      and p53 in tissues of skin cancer patients in placebo group had no significant
      changes (p>0.05). The vitamin B3 deficiency in skin cancer patients was
      positively correlated with the expressions of HIF-1alpha and p53. CONCLUSIONS:
      The expression levels of HIF-1alpha and p53 in tissues of skin cancer patients
      are significantly increased compared with those in skin tissues of healthy
      people, and the changes in their expressions are positively correlated with the
      vitamin B3 deficiency. Supplementing vitamin B3 has a certain protective effect
      on skin cancer patients.

PMID- 29064207
TI  - [PARENT'S AND CHILDREN'S BEHAVIOR AND KNOWLEDGE ABOUT ORAL HEALTH].
AB  - Responsible health behavior plays an important role in every individual. Oral
      health quality results from the level ofinformation available, attitudes, habits
      and nutrition. Family is the most important environment where children can
      acquireknowledge, attitudes and habits related to oral health. The aim of the
      study was to compare the habits of parents andchildren related to their oral
      health, and to conclude how parental behavior influences oral health of their
      children. Thestudy included 101 parent-child pairs (age 11-15 years), their
      knowledge and behavior according to their oral hygiene,fluoro-prophylaxis and
      nutrition assessed by anonymous questionnaire. Oral health of parents was
      estimated according totheir tooth loss and compensation, while oral health of
      children was assessed by dental examination. A total of 101 child-parentpairs
      were included. Most children were excellent pupils (43.56%). In the group of
      parents, most participants weremothers (73.27%). Most parents had high school
      education (65.35%) and were employed (61.62%), and most perceivedthemselves to be
      living with average financial situation (86%). A comparable proportion of parents
      (95%) and children(87%) believed that it was necessary to wash teeth at least
      twice a day (p=0.125) and most of them thought it necessary tobrush teeth for 1-3
      minutes (57% of children and 57.43% of parents; p=0.599). The majority of
      children (56%) and parents(72%) considered it necessary to use dental floss with
      a toothbrush and toothpaste (p=0.065), while 63% of children and71.72% of parents
      believed that toothpaste contained fluoride (p=0.156). Most of the parents
      (72.3%) and children (65.35%)brushed teeth in the morning and at bedtime
      (p=0.167) for 1-3 minutes (p=0.098). About 30% of parents and children usedthe
      handler for brushing teeth (p=1). Most children (86.32%) and parents (92.1%) had
      3-5 meals a day (p=0.181), and 80%of them had their teeth examined by a dentist
      the year before (p=0.658). The children believing that teeth should be
      brushedonly in the morning have a 3.38-fold greater chance to develop tooth
      disorders (DMFT >0; p=0.004). Those that do notknow that caries and periodontal
      diseases can be prevented have a 26.3-fold greater chance to develop caries
      comparedto those who are aware of it. Children of parents who only brush their
      teeth in the morning have a 25 times higher chanceof developing CEP >0 as
      compared with those that brush their teeth after each meal (p=0.016). Children of
      parents whogive them money to buy snacks are 2.9 times more likely to develop CEP
      >0 (p=0.01) compared to children without moneyfor snack. Children of parents who
      feel that their health is not good have 3.9 times higher chance of developing CEP
      >0as compared to those whose parents think they have a neat bite (p=0.017). Oral
      hygiene in Croatia is still not at a level ofthe standards in Western countries.
      Ignorance about oral hygiene and irresponsible health behavior are the main
      causesof the poor condition of the teeth. Results of this study showed the close
      relationship between family attitudes aboutoral hygiene, as children follow their
      parents' habits and behavior. In conclusion, by educating parents, we influence
      theirchildren's behavior and knowledge about oral health, and this is the way
      that health workers should plan interventions toprevent oral diseases.

PMID- 29064208
TI  - [ACUTE PAIN MANAGEMENT IN PATIENT ON OPIOID SUBSTITUTION THERAPY WITHMETHADONE OR
      BUPRENORPHINE].
AB  - The result of the increase in drug abuse is a growing number of patients
      receiving methadone or buprenorphinesubstitution therapy. Physicians are
      increasingly confronted with patients on substitution therapy at the time when
      theyare developing acute pain conditions or when they need surgery. Although pain
      has sensory qualities, it is a very personaland complex experience. The intensity
      and duration of pain are influenced by numerous factors. Poorly controlled
      painleads to unnecessary suffering of the patients with the possibility of
      permanent changes in behavior and reduced qualityof life. Efficacious pain
      treatment is considered a basic right of every patient. Because of the complex
      mechanisms of theemergence and transmission of pain and the emotional components
      that are involved in the experience of pain, appropriatepain relief in patients
      on substitution therapy is a major challenge for both the physicians and the
      patients. The article givesan overview of issues related to the treatment of
      acute pain and perioperative treatment in patients on substitution therapywith
      methadone and buprenorphine. The article highlights the wrong common
      misconception about pain treatment in thesepatients, which also are the most
      common cause of their inadequate treatment.

PMID- 29064209
TI  - [DWI MAGNETIC RESONANCE IN CHARACTERIZATION OF FOCAL LIVER LESIONS].
AB  - The aim of this study was to examine the possibilities of measuring ADC/DWI
      values with the ROI method for precisedifferentiation of focal liver lesions from
      normal liver parenchyma. The study included 100 liver lesions sized >=1 cm,
      previouslydetected in patients by ultrasound and computed tomography. It is done
      by measuring the diffusion coefficient ADC folder(MRI 3T), setting the ROI on the
      periphery of hepatic lesions, on the liver parenchyma around the focal hepatic
      lesions andon liver parenchyma that is distant to hepatic lesions. In our study,
      difference between the average ADC value of focalliver lesions (1.24 x10(-3)
      mm(2)/s) and normal liver parenchyma around focal liver lesions (1.001x10(-3)
      mm(2)/s) was statisticallyconfirmed. There was statistically proven difference in
      the average ADC values between normal liver parenchyma aroundfocal lesions and
      liver parenchyma located distant from focal lesions of (1.003x10-3 mm2/s).
      Wilcoxon rank test yieldeddifferences in the average (median) ADC values between
      total lesions in patients and liver parenchyma directly aroundfocal lesions
      (p<0.0005). Wilcoxon rank test showed no differences in the average (median) ADC
      between liver parenchymadirectly around focal lesions and distant of focal
      hepatic lesions (p<0.0005). The results obtained for each focal liver lesionwere
      compared with histopathology findings obtained by puncture or surgery, and for
      cystic lesions radiological follow upwas sufficient. For all liver lesions, the
      resulting overall DWI/ADC sensitivity was 92% and specificity 77%. Kendall's tau
      bcoefficient of concordance showed a statistically significant correlation
      between our DWI diagnosis and histopathologyverification for all liver lesions
      (p<0.0005). He mangiomas and cysts showed greatest difference in ADC values as
      comparedwith healthy liver. ADC values of hepatocellular carcinoma (HCC) and the
      surrounding normal liver parenchyma were notstatistically different, which can be
      explained by similarities in their cell structure. Related articles conclude that
      DWI hasinadequate sensitivity in detecting HCC, explaining this minimal
      difference in cellularity of well differentiated HCC and liverparenchyma. DWI/ADC
      has the potential to differentiate and reliably define the limits of focal
      lesions of the normal liverparenchyma. ADC delimitation of focal lesions of the
      liver parenchyma is most reliable for hemangiomas and cysts, whileADC
      delimitation of HCC can pose diagnostic difficulties.

PMID- 29064210
TI  - [SURGICAL TREATMENT OF THYROID GLAND IN ELDERLY PATIENTS: OUR EXPERIENCES].
AB  - The share of elderly persons in the population is growing rapidly and
      continuously. Requirements for their surgical treatmentare increasing and so is
      the number of published papers on the safety and success of some surgical
      procedures performedin these patients. The present study included 183 patients
      aged >=65 out of 897 patients surgically treated for thyroid glanddiseases. They
      were divided into two groups (group 1 aged 65-69 and group 2 aged >=70) in order
      to determine between-groupdifferences in the indications, surgical strategy,
      final histopathologic analysis, preoperative physical status, numberof comorbid
      diseases and postoperative complications. Analysis of the results justified our
      decision to divide our patientsinto two groups of younger and older ones. In
      group 1, the indications for surgery were mostly benign changes (93.2%),whereas
      malignant, verified and suspected disease was considerably more frequent in group
      2 (21.8%), with a significantlyhigher percentage of compressive syndrome.
      Significant between-group differences were recorded in the preoperativephysical
      status (group 2: ASA III and IV, 73.8% and 5%, respectively), number of
      thyroidectomies performed (group 1,56.2% vs. group 2, 77.3%) and secondary
      hemithyroidectomy. A difference was also found in the number of surgical andnon
      surgical complications. The absence of a higher percentage of permanent
      complications, hypocalcemia and recurrentlaryngeal nerve paralysis, in total and
      by groups, confirmed that surgical treatment of thyroid gland diseases can
      beconsidered safe and successful in older age groups, regardless of the between
      group differences observed.

PMID- 29064211
TI  - [RARE LOCALIZATION OF OSTEOID OSTEOMA--DISTAL PHALANX OF THE RING FINGER].
AB  - With this clinical observation we would like to bring to mind osteoid osteoma as
      a possible cause of problems of distalphalanx of the fingers. Osteoid osteoma
      occurs rarely at this location and has atypical presentation. The main
      symptomsare swelling and redness of the fingertip with nail deformity, while
      typical night pain may not be present. Unusual clinicaland x-ray presentation of
      tumor in this localization can make diagnosis of osteoid osteoma very difficult.
      A 20-year-oldpatient reported pain in the fingertip of his right ring finger
      persisting for five years. Swelling and redness of the fingertipcombined with
      nail deformity was also present. X-rays showed osteolysis in the base of distal
      phalanx. Magnetic resonanceimaging showed suspicion of osteoid osteoma, which was
      confirmed by computed tomography (CT). We performedsurgical removal of osteoid
      osteoma in February 2014. The tumor was approached by longitudinal incision on
      the lateralside of the distal phalanx of the ring finger and the basal part of
      distal phalanx was cut with a small chisel to enable accessto cystic change of
      the bone. Tumor removal with excochleation was performed and the material thus
      obtained was sentfor histopathologic analysis. After surgery, the ring finger was
      immobilized in a plaster splint for a three-week period. Afterremoval of
      immobilization, the patient was referred to physical therapy consisting of
      individual exercises in order to obtainthe full range of motion in all joints of
      the hands and strengthen hand and forearm muscles. After surgical removal of
      osteoidosteoma, all symptoms disappeared completely. Histopathologic findings
      confirmed the diagnosis of osteoid osteoma.After physical therapy, he returned to
      daily activities without any problems. On regular follow ups at 3, 6 and 12
      months aftersurgery, clinical findings were normal and the patient had no pain or
      discomforts. Full recovery was shown by the result ofthe DASH questionnaire three
      months after the procedure. Preoperative DASH score 54.4 decreased to 0. Distal
      phalanx ofthe finger is a very rare localization of osteoid osteoma, and typical
      night pain may not be present. In addition, appearanceon x-rays is not typical.
      Instead of central enlightenment surrounded with sclerosis, x-rays usually show a
      lytic lesion. Forthis reason, it may be difficult to make the diagnosis of
      osteoid osteoma. The main symptom is permanent pain, swellingand redness of the
      finger, with nail deformity. The imaging method of choice is CT, which must be
      performed with thin layersof 1 to 2 mm. Furthermore, cooperation of surgeon and
      radiologist is extremely important to reach the accurate diagnosis.Many treatment
      options are described in the literature, such as CT-guided percutaneous
      thermocoagulation, destructionof lesions with alcohol, or CT-guided
      radiofrequency ablation. However, due to the proximity of neurovascular
      structures,tendons and joints, the best method for treatment osteoid osteoma in
      distal phalanx of the fingers is surgical excision orexcochleation. Our
      conclusion is that one should always bear in mind that osteoid osteoma can be the
      cause of swellingof distal phalanx of the finger with nail deformity, and pain
      that alleviated with the use of non-steroidal anti-infl ammatorydrugs. Surgical
      excision or excochleation is the best method for the treatment osteoid osteoma of
      distal phalanx of thefinger.

PMID- 29064213
TI  - [Letter].

PMID- 29064212
TI  - [Letter].

PMID- 29064214
TI  - Aliens Among Us.

PMID- 29064215
TI  - Brands and Independent Contractors.

PMID- 29064216
TI  - Children's Oral Health Disparities Persist Despite Equal Dental Care Access.

PMID- 29064217
TI  - Study Estimates Health Impact of UK Soft Drinks Levy.

PMID- 29064218
TI  - Fossilized Teeth Reveal Much About Ancestors.

PMID- 29064219
TI  - Dental Implant Coatings Help Prevent Infection.

PMID- 29064220
TI  - The Management of Infections and the Use of Antibiotic Prophylaxis by Dentists: A
      Review of the Evidence.
AB  - Dentistry plays an important role in managing the antibiotic resistanceproblem.
      Guidelines for the use of antibiotics for prevention of endocarditis,prosthetic
      joint infections and other medical conditions have changed
      frequently.Unfortunately, the original guidelines and subsequent changes were
      often madethrough consensus opinions and not evidence based. Clinical decisions
      on the use ofantibiotics must be made on the basis of the scientific evidence
      with knowledge ofthe most current guidelines and indications.

PMID- 29064221
TI  - Management of Mandibular Fractures in Pediatric Patients With Conservative
      Technique: A Case Series.
AB  - The management of fractures in children is complex compared to that ofadults
      because of greater elasticity of bone, presence of tooth buds, faster healing
      rate,potential for future growth and lesser co-operative ability. Fractures of
      the mandiblein children are conventionally treated by circummandibular wiring.
      This paperreports a variation in the technique of using circummandibular wiring
      with acrylicsplints in the conservative treatment of mandibular fractures in two
      pediatric patients.

PMID- 29064223
TI  - Through Treatment Plans Build Patient Trust.

PMID- 29064222
TI  - Ex Vivo Assessment of Photodynamic Therapy in Achieving Microbial Reduction.
AB  - The study was to assess the effects of photodynamic therapy (PDT)on root canals
      contaminated by Enterococcus faecalis (E. faecalis). PDT wasperformed with 0.005%
      methylene blue dye and with a low-intensity red emissionlaser. Microbiological
      samples were collected before, immediately and 72 hoursafter instrumentation.
      Although PDT performed with the chosen light parameterspromoted additional
      microbial reduction, this therapy did not achieve a statisticallysignificant
      reduction of E. faecalis.

PMID- 29064224
TI  - Single-Shot Top-Down Proteomics with Capillary Zone Electrophoresis-Electrospray
      Ionization-Tandem Mass Spectrometry for Identification of Nearly 600 Escherichia
      coli Proteoforms.
AB  - Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry
      (CZE-ESI-MS/MS) has been recognized as an invaluable platform for top-down
      proteomics. However, the scale of top-down proteomics using CZE-MS/MS is still
      limited due to the low loading capacity and narrow separation window of CZE. In
      this work, for the first time we systematically evaluated the dynamic pH junction
      method for focusing of intact proteins during CZE-MS. The optimized dynamic pH
      junction-based CZE-MS/MS approached a 1 MUL loading capacity, 90 min separation
      window, and high peak capacity (~280) for characterization of an Escherichia coli
      proteome. The results represent the largest loading capacity and the highest peak
      capacity of CZE for top-down characterization of complex proteomes. Single-shot
      CZE-MS/MS identified about 2800 proteoform-spectrum matches, nearly 600
      proteoforms, and 200 proteins from the Escherichia coli proteome with spectrum
      level false discovery rate (FDR) less than 1%. The number of identified
      proteoforms in this work is over three times higher than that in previous single
      shot CZE-MS/MS studies. Truncations, N-terminal methionine excision, signal
      peptide removal, and some post-translational modifications including oxidation
      and acetylation were detected.

PMID- 29064226
TI  - Quick Activation of Nanoporous Anatase TiO2 as High-Rate and Durable Anode
      Materials for Sodium-Ion Batteries.
AB  - To understand the slow capacity activation behavior of anatase TiO2 as a sodium
      ion battery anode during cycling, a nanoporous configuration was designed and
      prepared. On the basis of the comprehension of the Na-ion storage mechanism, the
      behavior is demonstrated to be related with the gradual formation of amorphous
      phase resulting from the phase transition during discharge. In addition, the
      level of phase transition is determined by the discharge rates and cycle numbers,
      which strongly affects the electrochemical performance of anatase TiO2. Via a
      quick formation process of the amorphous phase in the initial cycles, the
      capacity activation is accelerated, and high initial capacity is achieved with no
      fading after 500 cycles. Particularly, anatase TiO2 displays surprisingly unique
      properties in the fast charge (even at 20 C, 6.7 A g-1) mode, delivering a 179 mA
      h g-1 charge capacity. This study is significant for the comprehensive
      understanding of the controversial sodium storage mechanisms and unclear special
      behaviors occurring in anatase TiO2, thus greatly contributing to better guidance
      on the computational studies and experiment technologies for further performance
      promotion.

PMID- 29064225
TI  - Comprehensive Ion Mobility Calibration: Poly(ethylene oxide) Polymer Calibrants
      and General Strategies.
AB  - Ion mobility (IM) is now a well-established and fast analytical technique. The IM
      hardware is constantly being improved, especially in terms of the resolving
      power. The Drift Tube (DTIMS), the Traveling Wave (TWIMS), and the Trapped Ion
      Mobility Spectrometry (TIMS) coupled to mass spectrometry are used to determine
      the Collision Cross-Sections (CCS) of ions. In analytical chemistry, the CCS is
      approached as a descriptor for ion identification and it is also used in physical
      chemistry for 3D structure elucidation with computational chemistry support. The
      CCS is a physical descriptor extracted from the reduced mobility (K0)
      measurements obtainable only from the DTIMS. TWIMS and TIMS routinely require a
      calibration procedure to convert measured physical quantities (drift time for
      TWIMS and elution voltage for TIMS) into CCS values. This calibration is a
      critical step to allow interinstrument comparisons. The previous calibrating
      substances lead to large prediction bands and introduced rather large
      uncertainties during the CCS determination. In this paper, we introduce a new IM
      calibrant (CCS and K0) using singly charged sodium adducts of poly(ethylene
      oxide) monomethyl ether (CH3O-PEO-H) for positive ionization in both helium and
      nitrogen as drift gas. These singly charged calibrating ions make it possible to
      determine the CCS/K0 of ions having higher charge states. The fitted calibration
      plots exhibit larger coverage with less data scattering and significantly
      improved prediction bands and uncertainties. The reasons for the improved CCS/K0
      accuracy, advantages, and limitations of the calibration procedures are also
      discussed. A generalized IM calibration strategy is suggested.

PMID- 29064227
TI  - Simple One-Pot Synthesis of Fully Biobased Unsaturated Polyester Resins Based on
      Itaconic Acid.
AB  - For the preparation of fully biobased unsaturated polyester resins (UPRs), the
      replacement of styrene with alternate nonpetroleum-based monomers turned out to
      be one of the most challenging tasks. Its complexity lies in the fact that
      reactive diluents (RD) have to have low viscosity and volatility, good
      compatibility with prepolymer, and capability to homopolymerize and copolymerize
      with its unsaturations. In this context, we directed our efforts to develop fully
      biobased UPRs using the dialkyl itaconates as an alternative to styrene.
      Therefore, a series of 100% biobased UPRs were prepared from itaconic acid and
      1,2-propandiol and diluted by dialkyl itaconates. The resins were characterized
      by Fourier transform infrared spectroscopy, NMR, volatility, and viscosity
      measurements, while the cured samples were characterized by dynamic mechanical
      properties, thermomechanical analysis, thermogravimetric analysis data, and
      tensile tests. The influence of RD structure on the properties of cured samples
      was discussed in detail. It was shown that the prepared resins had evaporation
      rates of dialkyl itaconates of several orders of magnitude less compared to
      styrene. The cured resins with dimethyl itaconate showed comparable or even
      better thermal and mechanical properties compared to the one with styrene. This
      investigation showed that itaconic acid and dialkyl itaconates are promising
      bioresources for the preparation of fully biobased UPRs for mass consumption.

PMID- 29064228
TI  - Group 6 Dihapto-Coordinate Dearomatization Agents for Organic Synthesis.
AB  - This review covers publications ranging from 2005 to 2017 concerning the organic
      reactions of aromatic ligands eta2-coordinated to tungsten or molybdenum and the
      use of these reactions in the synthesis of novel organic substances. An emphasis
      is placed on C-C bond-forming reactions using conventional building blocks of
      organic synthesis such as acetals, enolates, Michael acceptors, acylating
      reagents, and activated aromatics. Substrates activated by the metal include
      arenes, pyridines, pyrroles, pyrimidines, furans, and thiophenes. General
      reactivity patterns are elucidated, as well as stereochemical preferences. These
      trends are compared to those of osmium and rhenium forebears as well as to the
      reactivity patterns of other methods of stoichiometric transition-metal-based
      dearomatization (i.e., eta6-arene complexes).

PMID- 29064229
TI  - Validating Quantitative Untargeted Lipidomics Across Nine Liquid Chromatography
      High-Resolution Mass Spectrometry Platforms.
AB  - Liquid chromatography-mass spectrometry (LC-MS) methods are most often used for
      untargeted metabolomics and lipidomics. However, methods have not been
      standardized as accepted "best practice" documents, and reports lack
      harmonization with respect to quantitative data that enable interstudy
      comparisons. Researchers use a wide variety of high-resolution mass spectrometers
      under different operating conditions, and it is unclear if results would yield
      different biological conclusions depending on the instrument performance. To this
      end, we used 126 identical human plasma samples and 29 quality control samples
      from a nutritional intervention study. We investigated lipidomic data
      acquisitions across nine different MS instruments (1 single TOF, 1 Q/orbital ion
      trap, and 7 QTOF instruments). Sample preparations, chromatography conditions,
      and data processing methods were kept identical. Single-point internal standard
      calibrations were used to estimate absolute concentrations for 307 unique lipids
      identified by accurate mass, MS/MS spectral match, and retention times.
      Quantitative results were highly comparable between the LC-MS platforms tested.
      Using partial least-squares discriminant analysis (PLS-DA) to compare results
      between platforms, a 92% overlap for the most discriminating lipids based on
      variable importance in projection (VIP) scores was achieved for all lipids that
      were detected by at least two instrument platforms. Importantly, even the
      relative positions of individual samples on the PLS-DA projections were
      identical. The key for success in harmonizing results was to avoid ion saturation
      by carefully evaluating linear dynamic ranges using serial dilutions and
      adjusting the resuspension volume and/or injection volume before running actual
      study samples.

PMID- 29064230
TI  - Development of Dopant-Free Donor-Acceptor-type Hole Transporting Material for
      Highly Efficient and Stable Perovskite Solar Cells.
AB  - In perovskite solar cells (PSCs), overlying hole transporting materials (HTMs)
      are important for achieving high efficiencies as well as protecting perovskite
      active layers from degradation factors. This study reports the synthesis of a
      dopant-free HTM based on a D'-A-D-A-D-A-D' (D, D': electron donor, A: electron
      acceptor) conjugated structure and incorporation of the HTM into a PSC. The
      resulting PSC exhibits a high efficiency of 17.3%, which is comparable to that of
      the device based on doped spiro-OMeTAD HTM, and exhibits much improved stability:
      without encapsulation, the PSC based on the new HTM was found to retain 80% of
      its initial performance over 500 h under the conditions of 60% relative
      humidity/1 sun light-soaking without encapsulation. The high performance is
      attributed to efficient hole-extraction/collection and hole transport. We
      demonstrate that the extended pi-structure of the D'-A-D-A-D-A-D'-type HTM slows
      moisture intrusion and protects the perovskite layer better than smaller D-A-type
      molecules. The improved stability is primarily due to the hydrophobic nature of
      the HTM; the relatively large pi-conjugated molecule forms denser films, which
      effectively decrease the spaces between the molecules and retard water intrusion.
      The dopant-free D-A-type HTM with an extended pi-structure is effective not only
      in improving device efficiency, but also device stability.

PMID- 29064232
TI  - Correction to Structure-activity Relationships for Rates of Aromatic Amine
      Oxidation by Manganese Dioxide.

PMID- 29064233
TI  - Micro-Intertexture Carbon-Free Iron Sulfides as Advanced High Tap Density Anodes
      for Rechargeable Batteries.
AB  - Numerous materials have been considered as promising electrode materials for
      rechargeable batteries; however, developing efficient materials to achieving good
      cycling performance and high volumetric energy capacity simultaneously remains a
      great challenge. Considering the appealing properties of iron sulfides, which
      include low cost, high theoretical capacity, and favorable electrochemical
      conversion mechanism, in this work, we demonstrate the feasibility of carbon-free
      microscale Fe1-xS as high-efficiency anode materials for rechargeable batteries
      by designing hierarchical intertexture architecture. The as-prepared intertexture
      Fe1-xS microspheres constructed from nanoscale units take advantage of both the
      long cycle life of nanoscale units and the high tap density (1.13 g cm-3) of the
      micro-intertexture Fe1-xS. As a result, high capacities of 1089.2 mA h g-1
      (1230.8 mA h cm-3) and 624.7 mA h g-1 (705.9 mA h cm-3) were obtained after 100
      cycles at 1 A g-1 in Li-ion and Na-ion batteries, respectively, demonstrating one
      of the best performances for iron sulfide-based electrodes. Even after deep
      cycling at 20 A g-1, satisfactory capacities could be retained. Related results
      promote the practical application of metal sulfides as high-capacity electrodes
      with high rate capability for next-generation rechargeable batteries.

PMID- 29064231
TI  - Chiral Measurement of Aspartate and Glutamate in Single Neurons by Large-Volume
      Sample Stacking Capillary Electrophoresis.
AB  - d-Amino acids (d-AAs) are endogenous molecules found throughout the metazoan, the
      functions of which remain poorly understood. Measurements of low abundance and
      heterogeneously distributed d-AAs in complex biological samples, such as cells
      and multicellular structures of the central nervous system (CNS), require the
      implementation of sensitive and selective analytical approaches. In order to
      measure the d- and l-forms of aspartate and glutamate, we developed and applied a
      stacking chiral capillary electrophoresis (CE) with laser-induced fluorescence
      detection method. The achieved online analyte preconcentration led to a 480-fold
      enhancement of detection sensitivity relative to capillary zone electrophoresis,
      without impacting separation resolution or analysis time. Additionally, the
      effects of inorganic ions on sample preconcentration and CE separation were
      evaluated. The approach enabled the relative quantification of d-aspartate and d
      glutamate in individual neurons mechanically isolated from the CNS of the sea
      slug Aplysia californica, a well characterized neurobiological model. Levels of
      these structurally similar d-AAs were significantly different in subpopulations
      of cells collected from the investigated neuronal clusters.

PMID- 29064234
TI  - Two-Photon Spectra of Chlorophylls and Carotenoid-Tetrapyrrole Dyads.
AB  - We present a direct comparison of two-photon spectra of various carotenoid
      tetrapyrrole dyads and phthalocyanines (Pc) as well as chlorophylls (Chl) in the
      spectral range between 950 and 1360 nm, corresponding to one-photon spectra
      between 475 and 680 nm. For carotenoids (Car) with 8, 9, or 10 conjugated double
      bonds, the two-photon absorption cross section of states below the optical
      allowed carotenoid S2 is at least about 3-10 times higher than that of Pc or
      chlorophyll a and b at 550/1100 nm. A quantitative comparison of spectra from Pc
      with and without carotenoids of eight and nine conjugated double bonds confirms
      energy transfer from optically forbidden carotenoid states to Pc in these dyads.
      When considering that less than 100% efficient energy transfer reduces the two
      photon contribution of the carotenoids in the spectra, the actual Car two-photon
      cross sections relative to Chl/Pc are even higher than a factor of 3-10. In
      addition, strong spectroscopic two-photon signatures at energies below the
      optical allowed carotenoid S2 state support the presence of additional optical
      forbidden carotenoid states such as S*, Sx, or, alternatively, contributions from
      higher vibronic or hot S1 states dominating two-photon spectra or energy transfer
      from the carotenoids. The onset of these states is shifted about 1500-3500 cm-1
      to lower energies in comparison to the S2 states. Our data provides evidence that
      two-photon excitation of the carotenoid S*, Sx, or hot S1 states results in
      energy transfer to tetrapyrroles or chlorophylls similar to that observed with
      the Car S1 two-photon excitation.

PMID- 29064235
TI  - Single Cell Electrochemiluminescence Imaging: From the Proof-of-Concept to
      Disposable Device-Based Analysis.
AB  - We report here the development of coreactant-based electrogenerated
      chemiluminescence (ECL) as a surface-confined microscopy to image single cells
      and their membrane proteins. Labeling the entire cell membrane allows one to
      demonstrate that, by contrast with fluorescence, ECL emission is only detected
      from fluorophores located in the immediate vicinity of the electrode surface
      (i.e., 1-2 MUm). Then, to present the potential diagnostic applications of our
      approach, we selected carbon nanotubes (CNT)-based inkjet-printed disposable
      electrodes for the direct ECL imaging of a labeled plasma receptor overexpressed
      on tumor cells. The ECL fluorophore was linked to an antibody and enabled to
      localize the ECL generation on the cancer cell membrane in close proximity to the
      electrode surface. Such a result is intrinsically associated with the unique ECL
      mechanism and is rationalized by considering the limited lifetimes of the
      electrogenerated coreactant radicals. The electrochemical stimulus used for
      luminescence generation does not suffer from background signals, such as the
      typical autofluorescence of biological samples. The presented surface-confined
      ECL microscopy should find promising applications in ultrasensitive single cell
      imaging assays.

PMID- 29064236
TI  - Toward Fractioning of Isomers through Binding-Induced Acceleration of Azobenzene
      Switching.
AB  - The E/Z isomerization process of a uracil-azobenzene derivative in which the
      nucleobase is conjugated to a phenyldiazene tail is studied in view of its
      ability to form triply H-bonded complexes with a suitably complementary 2,6
      diacetylamino-4-pyridine ligand. UV-vis and 1H NMR investigations of the
      photochemical and thermal isomerization kinetics show that the thermal Z -> E
      interconversion is 4-fold accelerated upon formation of the H-bonded complex. DFT
      calculations show that the formation of triple H-bonds triggers a significant
      elongation of the N?N double bond, caused by an increase of its pig* antibonding
      character. This results in a reduction of the N?N torsional barrier and thus in
      accelerated thermal Z -> E isomerization. Combined with light-controlled E -> Z
      isomerization, this enables controllable fractional tuning of the two
      configurational isomers.

PMID- 29064237
TI  - (Oxo)(Fluoro)-Aluminates in KF-Al2O3 System: Thermal Stability and Structural
      Correlation.
AB  - Precise investigation of part of the phase diagram of KF-Al2O3 system was
      performed in an experiment combining different techniques. Solidified mixtures of
      KF-Al2O3 were studied by X-ray powder diffraction and high-field solid-state NMR
      spectroscopy over a wide range of compositions. To help with the interpretation
      of the NMR spectra of the solidified samples found as complex admixtures, we
      synthesized the following pure compounds: KAlO2, K2Al22O34, alpha-K3AlF6, KAlF4,
      and K2Al2O3F2. These compounds were then characterized using various solid-state
      NMR techniques, including MQ-MAS and D-HMQC. NMR parameters of the pure compounds
      were finally determined using first-principles density functional theory
      calculations. The phase diagram of KF-Al2O3 with the alumina content up to 30 mol
      % was determined by means of thermal analysis. Thermal analysis was also used for
      the description of the thermal stability of one synthesized compound, K2Al2O3F2.

PMID- 29064238
TI  - Cobalt Tetrabutano- and Tetrabenzotetraarylporphyrin Complexes: Effect of
      Substituents on the Electrochemical Properties and Catalytic Activity of Oxygen
      Reduction Reactions.
AB  - Three series of cobalt tetraarylporphyrins were synthesized and characterized by
      electrochemistry and spectroelectrochemistry. The investigated compounds have the
      general formula (TpYPP)Co, butano(TpYPP)CoII, and benzo(TpYPP)CoII, where TpYPP
      represents the dianion of the meso-substituted porphyrin, Y is a CH3, H, or Cl
      substituent on the para position of the four phenyl rings, and butano and benzo
      are respectively the beta- and beta'-substituted groups on the four pyrrole rings
      of the compound. Each porphyrin undergoes one or two reductions depending upon
      the meso substituent and solvent utilized. Two irreversible reductions are
      observed for (TpYPP)CoII and butano(TpYPP)CoII in CH2Cl2 containing 0.1 M tetra-n
      butylammonium perchlorate; the first leads to the formation of a highly reactive
      cobalt(I) porphyrin, which can then rapidly react with a solvent to give a
      CoIIICH2Cl as the product. Only one reversible reduction is seen for
      benzo(TpYPP)CoII under the same solution conditions, and the one-electron
      reduction product is assigned as a cobalt(II) porphyrin pi-anion radical. Three
      oxidations can be observed for each examined compound in CH2Cl2. The first
      oxidation is metal-centered for the (TpYPP)Co and benzo(TpYPP)CoII derivatives,
      leading to generation of a cobalt(III) porphyrin with an intact pi-ring system,
      but this redox process is ring-centered in the case of butano(TpYPP)CoII and
      gives a CoII pi-cation radical product. Each porphyrin was also examined as a
      catalyst for oxygen reduction reactions (ORRs) when adsorbed on a graphite
      electrode in 1.0 M HClO4. The number of electrons transferred (n) during ORRs is
      2.0 for the butano(TpYPP)CoII derivatives, consistent with only H2O2 being
      produced as a product for the reaction with O2. However, the reduction of O2
      using the cobalt benzoporphyrins as catalysts gave n values between 2.6 and 3.1
      under the same solution conditions, thus producing a mixture of H2O and H2O2 as
      the reduction product. This result indicates that the beta and beta' substituents
      have a significant effect on the catalytic properties of the cobalt porphyrins
      for ORRs in acid media.

PMID- 29064239
TI  - Dynamics of Coupled Electron-Boson Systems with the Multiple Davydov D1 Ansatz
      and the Generalized Coherent State.
AB  - The dynamics of a coupled electron-boson system is investigated by employing a
      multitude of the Davydov D1 trial states, also known as the multi-D1 Ansatz, and
      a second trial state based on a superposition of the time-dependent generalized
      coherent state (GCS Ansatz). The two Ansatze are applied to study population
      dynamics in the spin-boson model and the Holstein molecular crystal model, and a
      detailed comparison with numerically exact results obtained by the (multilayer)
      multiconfiguration time-dependent Hartree method and the hierarchy equations of
      motion approach is drawn. It is found that the two methodologies proposed here
      have significantly improved over that with the single D1 Ansatz, yielding
      quantitatively accurate results even in the critical cases of large energy biases
      and large transfer integrals. The two methodologies provide new effective tools
      for accurate, efficient simulation of many-body quantum dynamics thanks to a
      relatively small number of parameters which characterize the electron-nuclear
      wave functions. The wave-function-based approaches are capable of tracking
      explicitly detailed bosonic dynamics, which is absent by construct in approaches
      based on the reduced density matrix. The efficiency and flexibility of our
      methods are also advantages as compared with numerically exact approaches such as
      QUAPI and HEOM, especially at low temperatures and in the strong coupling regime.

PMID- 29064240
TI  - Structural Evolution in BaSn2F5X (X = Cl, Br, I): A Family of Alkaline Earth
      Metal Tin Mixed Halides.
AB  - As the first family of Sn-based alkaline earth metal mixed halides, three new
      compounds, BaSn2F5X (X = Cl, Br, and I), are synthesized by hydrothermal method.
      These compounds are crystallized in the centrosymmetric space groups of P21/c,
      P4/nmm, and Pmma for BaSn2F5Cl, BaSn2F5Br, and BaSn2F5I, respectively, and their
      microscopic frameworks are all composed of the fundamental structural unit
      [SnF4]2- and its derivatives ([SnF4Cl]3- and [SnF5]3- groups). Interestingly, the
      structures in BaSn2F5X are significantly changed from one-dimensional (1D) to two
      dimensional (2D) and then to 1D motifs as X varies from Cl, Br, to I. Structural
      analysis combined with theoretical calculations reveals that the structural
      diversities are caused by the difference of ionic radius and electronegativity of
      X- anions as well as the orientation of the lone-pair electrons on Sn2+ cations.
      Moreover, the optical, electronic, and thermal properties for these three
      compounds are determined. This work provides a representative example to show how
      microscopic ions influence the structures, thus in favor of the design for new
      mixed halides, a type of important functional materials with many optoelectronic
      applications.

PMID- 29064241
TI  - Is C3N4 Chemically Stable toward Reactive Oxygen Species in Sunlight-Driven Water
      Treatment?
AB  - Reactive oxygen species (ROS) are key oxidants for the degradation of organic
      pollutants in sunlight-driven photocatalytic water treatment, but their
      interaction with the photocatalyst is easily ignored and, hence, is comparatively
      poorly understood. Here we show that graphitic carbon nitride (C3N4, a famous
      visible-light-responsive photocatalyst) is chemically stable toward ozone and
      superoxide radical; in contrast, hydroxyl radical (*OH) can tear the heptazine
      unit directly from C3N4 to form cyameluric acid and further release nitrates into
      the aqueous environment. The ratios of released nitrogen from nanosheet
      structured C3N4 and bulk C3N4 that finally exists in the form of NO3- reach 9.5
      and 6.8 mol % in initially ultrapure water, respectively, after 10 h treatment by
      solar photocatalytic ozonation, which can rapidly generate abundant *OH to attack
      C3N4. On a positive note, in the presence of organic pollutants which compete
      against C3N4 for *OH, the C3N4 decomposition has been completely or partially
      blocked; therefore, the stability of C3N4 under practical working conditions has
      been obviously preserved. This work supplements the missing knowledge of the
      chemical instability of C3N4 toward *OH and calls for attention to the potential
      deactivation and secondary pollution of catalysts in *OH-involved water treatment
      processes.

PMID- 29064242
TI  - Inferring Past Trends in Lake Water Organic Carbon Concentrations in Northern
      Lakes Using Sediment Spectroscopy.
AB  - Changing lake water total organic carbon (TOC) concentrations are of concern for
      lake management because of corresponding effects on aquatic ecosystem
      functioning, drinking water resources and carbon cycling between land and sea.
      Understanding the importance of human activities on TOC changes requires
      knowledge of past concentrations; however, water-monitoring data are typically
      only available for the past few decades, if at all. Here, we present a universal
      model to infer past lake water TOC concentrations in northern lakes across Europe
      and North America that uses visible-near-infrared (VNIR) spectroscopy on lake
      sediments. In the orthogonal partial least-squares model, VNIR spectra of surface
      sediment samples are calibrated against corresponding surface water TOC
      concentrations (0.5-41 mg L-1) from 345 Arctic to northern temperate lakes in
      Canada, Greenland, Sweden and Finland. Internal model-cross-validation resulted
      in a R2 of 0.57 and a prediction error of 4.4 mg TOC L-1. First applications to
      lakes in southern Ontario and Scotland, which are outside of the model's
      geographic range, show the model accurately captures monitoring trends, and
      suggests that TOC dynamics during the 20th century at these sites were primarily
      driven by changes in atmospheric deposition. Our results demonstrate that the
      lake water TOC model has multiregional applications and is not biased by
      postdepositional diagenesis, allowing the identification of past TOC variations
      in northern lakes of Europe and North America over time scales of decades to
      millennia.

PMID- 29064244
TI  - Thermodynamics of Indomethacin Adsorption to Phospholipid Membranes.
AB  - Using second-harmonic generation, we directly monitored adsorption of
      indomethacin, a nonsteroidal anti-inflammatory drug, to supported lipid bilayers
      composed of phospholipids of varying phase, cholesterol content, and head group
      charge without the use of extrinsic labels at therapeutically relevant aqueous
      concentrations. Indomethacin adsorbed to gel-phase lipids with a high binding
      affinity, suggesting that like other arylacetic acid-containing drugs, it
      preferentially interacts with ordered lipid domains. We discovered that
      adsorption of indomethacin to gel-phase phospholipids was endothermic and
      entropically driven, whereas adsorption to fluid-phase phospholipids was
      exothermic and enthalpically driven. As temperature increased from 19 to 34 
      degrees C, binding affinities to gel-phase lipids increased by 7-fold but
      relative surface concentration decreased to one-fifth of the original value. We
      also compared our results to the entropies reported for indomethacin adsorbed to
      surfactant micelles, which are used in drug delivery systems, and assert that
      adsorbed water molecules in the phospholipid bilayer may be buried deeper into
      the acyl chains and less accessible for disruption. The thermodynamic studies
      reported here provide mechanistic insight into indomethacin interactions with
      mammalian plasma membranes in the gastrointestinal tract and inform studies of
      drug delivery, where indomethacin is commonly used as a prototypical, hydrophobic
      small-molecule drug.

PMID- 29064247
TI  - In Situ Stimulation of Thiocyanate Biodegradation through Phosphate Amendment in
      Gold Mine Tailings Water.
AB  - Thiocyanate (SCN-) is a contaminant requiring remediation in gold mine tailings
      and wastewaters globally. Seepage of SCN--contaminated waters into aquifers can
      occur from unlined or structurally compromised mine tailings storage facilities.
      A wide variety of microorganisms are known to be capable of biodegrading SCN-;
      however, little is known regarding the potential of native microbes for in situ
      SCN- biodegradation, a remediation option that is less costly than engineered
      approaches. Here we experimentally characterize the principal biogeochemical
      barrier to SCN- biodegradation for an autotrophic microbial consortium enriched
      from mine tailings, to arrive at an environmentally realistic assessment of in
      situ SCN- biodegradation potential. Upon amendment with phosphate, the consortium
      completely degraded up to ~10 mM SCN- to ammonium and sulfate, with some evidence
      of nitrification of the ammonium to nitrate. Although similarly enriched in known
      SCN--degrading strains of thiobacilli, this consortium differed in its source
      (mine tailings) and metabolism (autotrophy) from those of previous studies. Our
      results provide a proof of concept that phosphate limitation may be the principal
      barrier to in situ SCN- biodegradation in mine tailing waters and also yield new
      insights into the microbial ecology of in situ SCN- bioremediation involving
      autotrophic sulfur-oxidizing bacteria.

PMID- 29064245
TI  - Organophosphonate-Bridged Polyoxometalate-Based Dysprosium(III) Single-Molecule
      Magnet.
AB  - A novel dysprosium(III)-containing polytungstoarsenate,
      [{(AsW9O33)3Dy2(H2O)4W4O9(H2O)}2(NH2(CH2PO3)2)]33-, comprising two identical
      subunits bridged by an organophosphonate ligand shows single-molecule-magnet
      (SMM) behavior. Magnetic studies reveal that this complex exhibits a butterfly
      shaped hysteresis loop up to 8 K, and a thermally activated energy barrier of
      101(5) K reached a breakthrough among all polyoxometalate-supported SMMs.

PMID- 29064248
TI  - Highly Efficient Room-Temperature Phosphorescence from Halogen-Bonding-Assisted
      Doped Organic Crystals.
AB  - The development of metal-free organic room temperature phosphorescence (RTP)
      materials has attracted increasing attention because of their applications in
      sensors, biolabeling (imaging) agents and anticounterfeiting technology, but
      remains extremely challenging owing to the restricted spin-flip intersystem
      crossing (ISC) followed by low-yield phosphorescence that cannot compete with
      nonradiative relaxation processes. Here, we report a facile strategy to realize
      highly efficient RTP by doping iodo difluoroboron dibenzoylmethane (I-BF2dbm-R)
      derivatives into a rigid crystalline 4-iodobenzonitrile (Iph-C=N) matrix. We
      found that halogen bonding between cyano group of Iph-C=N matrix and iodine atom
      of I-BF2dbm-R dopant is formed in doped crystals, i.e., Iph-C=N...I-BF2dbm-R,
      which not only suppresses nonradiative relaxation of triplets but also promotes
      the spin-orbit coupling (SOC). As a result, the doped crystals show intense RTP
      with an efficiency up to 62.3%. By varying the substituent group R in I-BF2dbm-R
      from electron donating -OCH3 to electron accepting -F, -CN groups, the ratio
      between phosphorescence and fluorescence intensities has been systematically
      increased from 3.8, 15, to 50.

PMID- 29064243
TI  - Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone
      Receptor with Broad beta Residue Distribution.
AB  - The parathyroid hormone receptor 1 (PTHR1) is a member of the B-family of GPCRs;
      these receptors are activated by long polypeptide hormones and constitute targets
      of drug development efforts. Parathyroid hormone (PTH, 84 residues) and PTH
      related protein (PTHrP, 141 residues) are natural agonists of PTHR1, and an N
      terminal fragment of PTH, PTH(1-34), is used clinically to treat osteoporosis.
      Conventional peptides in the 20-40-mer length range are rapidly degraded by
      proteases, which may limit their biomedical utility. We have used the PTHR1
      ligand system to explore the impact of broadly distributed replacement of alpha
      amino acid residues with beta-amino acid residues on susceptibility to
      proteolysis and agonist activity. This effort led us to identify new PTHR1
      agonists that contain alpha -> beta replacements throughout their sequences,
      manifest potent agonist activity in cellular assays, and display remarkable
      resistance to proteolysis, in cases remaining active after extended exposure to
      simulated gastric fluid. The strategy we have employed suggests a path toward
      identifying protease-resistant agonists of other B-family GPCRs.

PMID- 29064249
TI  - Why Do Simple Molecules with "Isolated" Phenyl Rings Emit Visible Light?
AB  - pi-Bonds connected with aromatic rings were generally believed as the standard
      structures for constructing highly efficient fluorophores. Materials without
      these typical structures, however, exhibited only low fluorescence quantum yields
      and emitted in the ultraviolet spectral region. In this work, three molecules,
      namely bis(2,4,5-trimethylphenyl)methane, 1,1,2,2-tetrakis(2,4,5
      trimethylphenyl)ethane, and 1,1,2,2-tetraphenylethane, with nonconjugated
      structures and isolated phenyl rings were synthesized and their photophysical
      properties were systematically investigated. Interestingly, the emission spectra
      of these three molecules could be well extended to 600 nm with high solid-state
      quantum yields of up to 70%. Experimental and theoretical analyses proved that
      intramolecular through-space conjugation between the "isolated" phenyl rings
      played an important role for this abnormal phenomenon.

PMID- 29064250
TI  - Mutations of Residues in Pocket P1 of a Cyclodipeptide Synthase Strongly Increase
      Product Formation.
AB  - Expression of a cyclodipeptide synthase gene from Nocardiopsis prasina (CDPS-Np)
      in Escherichia coli resulted in the formation of cyclo-(l-Tyr-l-Tyr) (1) as the
      minor and cyclo-(l-Tyr-l-Phe) (2) as the major products. Site-directed
      mutagenesis revealed a strong influence on product accumulation of the amino acid
      residues in pocket P1. An 8-fold increase in product formation for 1 and 10-fold
      for 2 were detected in the double mutant T82V_Y196F compared with the wild type.

PMID- 29064251
TI  - Nucleophilic Functionalizations of Aniline Derivatives: Aromatic Pummerer
      Reaction for Umpolung Halogenation and Hydroxylation on Benzene Ring.
AB  - In this paper, a metal-free protocol of nucleophilic ortho-halogenation and
      hydroxylation of anilines via an aromatic Pummerer process is reported.

PMID- 29064252
TI  - Hydrostatic Pressurization of Lung Surfactant Microbubbles: Observation of a
      Strain-Rate Dependent Elasticity.
AB  - The microbubble offers a unique platform to study lung surfactant mechanics at
      physiologically relevant geometry and length scale. In this study, we compared
      the response of microbubbles (~15 MUm initial radius) coated with pure
      dipalmitoyl-phosphatidylcholine (DPPC) versus naturally derived lung surfactant
      (SURVANTA) when subjected to linearly increasing hydrostatic pressure at
      different rates (0.5-2.3 kPa/s) at room temperature. The microbubbles contained
      perfluorobutane gas and were submerged in buffered saline saturated with
      perfluorobutane at atmospheric pressure. Bright-field microscopy showed that DPPC
      microbubbles compressed spherically and smoothly, whereas SURVANTA microbubbles
      exhibited wrinkling and smoothing cycles associated with buckling and collapse.
      Seismograph analysis showed that the SURVANTA collapse amplitude was constant,
      but the collapse rate increased with the pressurization rate. An analysis of the
      pressure-volume curves indicated that the dilatational elasticity increased
      during compression for both shell types. The initial dilatational elasticity for
      SURVANTA was nearly twice that of DPPC at higher pressurization rates (>1.5
      kPa/s), producing a pressure drop of up to 60 kPa across the film prior to
      condensation of the perfluorobutane core. The strain-rate dependent stiffening of
      SURVANTA shells likely arises from their composition and microstructure, which
      provide enhanced in-plane monolayer rigidity and lateral repulsion from surface
      associated collapse structures. Overall, these results provide new insights into
      lung surfactant mechanics and collapse behavior during compression.

PMID- 29064253
TI  - Macroscopic Quantum Tunneling in Superconducting Junctions of beta-Ag2Se
      Topological Insulator Nanowire.
AB  - We report on the fabrication and electrical transport properties of
      superconducting junctions made of beta-Ag2Se topological insulator (TI) nanowires
      in contact with Al superconducting electrodes. The temperature dependence of the
      critical current indicates that the superconducting junction belongs to a short
      and diffusive junction regime. As a characteristic feature of the narrow
      junction, the critical current decreases monotonously with increasing magnetic
      field. The stochastic distribution of the switching current exhibits the
      macroscopic quantum tunneling behavior, which is robust up to T = 0.8 K. Our
      observations indicate that the TI nanowire-based Josephson junctions can be a
      promising building block for the development of nanohybrid superconducting
      quantum bits.

PMID- 29064254
TI  - Strain-Dependent Edge Structures in MoS2 Layers.
AB  - Edge structures are low-dimensional defects unavoidable in layered materials of
      the transition metal dichalcogenides (TMD) family. Among the various types of
      such structures, the armchair (AC) and zigzag (ZZ) edge types are the most
      common. It has been predicted that the presence of intrinsic strain localized
      along these edges structures can have direct implications for the customization
      of their electronic properties. However, pinning down the relation between local
      structure and electronic properties at these edges is challenging. Here, we
      quantify the local strain field that arises at the edges of MoS2 flakes by
      combining aberration-corrected transmission electron microscopy (TEM) with the
      geometrical-phase analysis (GPA) method. We also provide further insight on the
      possible effects of such edge strain on the resulting electronic behavior by
      means of electron energy loss spectroscopy (EELS) measurements. Our results
      reveal that the two-dominant edge structures, ZZ and AC, induce the formation of
      different amounts of localized strain fields. We also show that by varying the
      free edge curvature from concave to convex, compressive strain turns into tensile
      strain. These results pave the way toward the customization of edge structures in
      MoS2, which can be used to engineer the properties of layered materials and thus
      contribute to the optimization of the next generation of atomic-scale electronic
      devices built upon them.

PMID- 29064255
TI  - Ultrafast Interlayer Electron Transfer in Incommensurate Transition Metal
      Dichalcogenide Homobilayers.
AB  - Two-dimensional materials, such as graphene, transition metal dichalcogenides,
      and phosphorene, can be used to construct van der Waals multilayer structures.
      This approach has shown potentials to produce new materials that combine novel
      properties of the participating individual layers. One key requirement for
      effectively harnessing emergent properties of these materials is electronic
      connection of the involved atomic layers through efficient interlayer charge or
      energy transfer. Recently, ultrafast charge transfer on a time scale shorter than
      100 fs has been observed in several van der Waals bilayer heterostructures formed
      by two different materials. However, information on the transfer between two
      atomic layers of the same type is rare. Because these homobilayers are essential
      elements in constructing multilayer structures with desired optoelectronic
      properties, efficient interlayer transfer is highly desired. Here we show that
      electron transfer between two monolayers of MoSe2 occurs on a picosecond time
      scale. Even faster transfer was observed in homobilayers of WS2 and WSe2. The
      samples were fabricated by manually stacking two exfoliated monolayer flakes. By
      adding a graphene layer as a fast carrier recombination channel for one of the
      two monolayers, the transfer of the photoexcited carriers from the populated to
      the drained monolayers was time-resolved by femtosecond transient absorption
      measurements. The observed efficient interlayer carrier transfer indicates that
      such homobilayers can be used in van der Waals multilayers to enhance their
      optical absorption without significantly compromising the interlayer transport
      performance. Our results also provide valuable information for understanding
      interlayer charge transfer in heterostructures.

PMID- 29064256
TI  - Long-Term Stability of Human Plasma Metabolites during Storage at -80  degrees C.
AB  - Prolonged storage of biospecimen can lead to artificially altered metabolite
      concentrations and thus bias data analysis in metabolomics experiments. To
      elucidate the potential impact of long-term storage on the metabolite profile, a
      pooled human plasma sample was aliquoted and stored at -80  degrees C. During a
      time period of five years, 1012 of the aliquots were measured with the Biocrates
      AbsoluteIDQ p180 targeted-metabolomics assay at 193 time points. Modeling the
      concentration courses over time revealed that 55 out of 111 metabolites remained
      stable. The statistically significantly changed metabolites showed on average an
      increase or decrease of +13.7% or -14.5%, respectively. In detail, increased
      concentration levels were observed for amino acids (mean: + 15.4%), the sum of
      hexoses (+7.9%), butyrylcarnitine (+9.4%), and some phospholipids mostly with
      chain lengths exceeding 40 carbon atoms (mean: +18.0%). Lipids tended to exhibit
      decreased concentration levels with the following mean concentration changes:
      acylcarnitines, -12.1%; lysophosphatidylcholines, -15.1%; diacyl
      phosphatidylcholines, -17.0%; acyl-alkyl-phosphatidylcholines, -13.3%;
      sphingomyelins, -14.8%. We conclude that storage of plasma samples at -80 
      degrees C for up to five years can lead to altered concentration levels of amino
      acids, acylcarnitines, glycerophospholipids, sphingomyelins, and the sum of
      hexoses. These alterations must be considered when analyzing metabolomics data
      from long-term epidemiological studies.

PMID- 29064257
TI  - Effect of Coadministered Water on the In Vivo Performance of Oral Formulations
      Containing N-Acetylcysteine: An In Vitro Approach Using the Dynamic Open Flow
      Through Test Apparatus.
AB  - The drug plasma profile after oral administration of immediate release dosage
      forms can be affected by the human gastrointestinal physiology, the formulation,
      and the drug itself. In this work, we investigated the in vivo and in vitro
      performance of two formulations (granules vs. tablet) containing the highly
      soluble drug N-Acetylcysteine (BCS class I). Thereby, special attention was paid
      to the effect of the dosage form and the coadministration of water on drug
      release. Interestingly, the in vivo results from a pharmacokinetic study with 11
      healthy volunteers indicated that the drug plasma concentrations were comparable
      for the tablet given with water as well as for the granules given with and
      without water. In order to mechanistically understand this outcome, we used a
      biorelevant dissolution test device, the dynamic open flow-through test
      apparatus. With the aid of this test apparatus, we were able to simulate
      biorelevant parameters, such as gastric emptying, hydrodynamic flow as well as
      physical stress. By this, it was possible to mimic the intake conditions of the
      clinical trial (i.e., drug intake with and without water). Whereas the
      experiments in the USP paddle apparatus revealed differences between the two
      formulations, we could not observe significant differences in the release
      profiles of the two formulations by using the dynamic open flow-through test
      apparatus. Even by considering the different intake conditions, drug release was
      slow and amounted to around 30% until simulated gastric emptying. These results
      suggest that dissolution was irrespective of coadministered water and the
      formulation. Despite the high aqueous solubility of N-Acetylcysteine, the
      limiting factor for drug release was the slow dissolution rate in relation to the
      gastric emptying rate under simulated gastric conditions. Thus, in case of
      administration together with water, large amounts of the drug are still present
      in the stomach even after complete gastric emptying of the water. Consequently,
      the absorption of the drug is largely controlled by the nature of gastric
      emptying of the remaining drug. The data of this study indicated that the water
      emptying kinetics are only determining drug absorption if drug release is rapid
      enough. If this is not the case, physiological mechanisms, such as the migrating
      motor complex, play an important role for oral drug delivery.

PMID- 29064258
TI  - New or presumed new left bundle branch block in patients with suspected ST
      elevation myocardial infarction.
AB  - AIMS: Using a comprehensive large prospective regional ST-elevation myocardial
      infarction (STEMI) system database, we evaluated the prevalence, clinical and
      angiographic characteristics, and outcomes in patients with ischemic symptoms and
      new or presumed new left bundle branch block (LBBB). We then tested a new
      hierarchical diagnosis and triage algorithm to identify more accurately new LBBB
      patients with an acute culprit lesion. METHODS AND RESULTS: From March 2003 to
      June 2013, 3903 consecutive STEMI patients were treated using the Minneapolis
      Heart Institute regional STEMI protocol including 131 patients (3.3%) with new
      LBBB. These patients had fewer culprit arteries (54.2% vs. 86.4%; P<0.001), were
      older, more commonly women, with a lower ejection fraction, and more frequently
      presented with cardiac arrest or heart failure than those without new LBBB. At 1
      year follow-up, all-cause mortality accounting for baseline differences was
      higher in patients with new LBBB (hazard ratio 1.73, 95% confidence interval 1.17
      2.58; P=0.007). The new algorithm yielded high sensitivity (97%) and negative
      predictive value (94%) for identification of a culprit lesion. Using the
      definition of new LBBB with either hemodynamically unstable features or Sgarbossa
      concordance criteria on electrocardiogram (ECG), 45% of new LBBB patients would
      have been treated as 'STEMI equivalent'. CONCLUSION: Patients with acute ischemic
      symptoms and new LBBB represent a high-risk population with unique clinical
      challenges. If validated in an independent dataset, the new algorithm may improve
      the diagnostic accuracy regarding reperfusion therapy for new LBBB patients.

PMID- 29064259
TI  - Editor's Choice-The cardiovascular implications of sedatives in the cardiac
      intensive care unit.
AB  - Patients admitted to the cardiac intensive care unit frequently develop multi
      organ system dysfunction associated with their cardiac disease. In many cases,
      invasive mechanical ventilation is required, which often necessitates sedation
      for patient-ventilator synchrony, reduction of work of breathing, and patient
      comfort. In this paper, we describe the use of common sedatives available in the
      endotracheally intubated critically ill patient and emphasize the clinical and
      cardiovascular effects. We review gamma-aminobutyric acid agonists such as
      etomidate, benzodiazepines, and propofol, the centrally acting alpha2-agonist
      dexmedetomidine, and the N-methyl-D-aspartate receptor antagonist ketamine.
      Additionally, we outline the use of opioids and their role in potentiating other
      sedatives. We note that some sedatives are associated with increased delirium
      rates, and emphasize that judicious strategies minimizing sedative use are
      associated with decreases in morbidity and mortality. We also discuss
      standardized sedation assessment scales and highlight the importance of sedation
      weaning. Finally, we offer recommendations for sedation use during therapeutic
      hypothermia, and discuss the use of adjuvant neuromuscular blocking agents.

PMID- 29064261
TI  - Risk assessment for infected endocarditis in Staphylococcus aureus bacteremia
      patients: When is transesophageal echocardiography needed?
AB  - AIMS: Echocardiography is the main technique for the diagnosis of endocarditis in
      patients with Staphylococcus aureus bacteremia (SAB), but a consensus about
      performing transthoracic echocardiography or transesophageal echocardiography
      (TEE) as first-line tests is currently lacking. Recently, a new scoring system
      has been proposed by Palraj et al. to guide the use of TEE in this population.
      Our aim was to validate this scoring system or modify it, if necessary. METHODS
      AND RESULTS: Data from SAB patients admitted from 2012 to 2014 were collected. We
      tested the Palraj scores to stratify patients' risk for endocarditis. Moreover,
      we analyzed our population to identify any other possible clinical predictors of
      endocarditis not included in the score. Endocarditis was diagnosed in 38 of 205
      patients (18.5%). Palraj's score was effective in the detection of patients at
      high risk of endocarditis. In addition, we identified the presence of cardiac
      devices, prolonged bacteremia and intravenous drug abuse (IVDA) as elements
      strongly correlated with endocarditis. Two scoring systems (Day-1 and Day-5) were
      derived including IVDA as a variable. Using a Day-1 cut-off value >=5 and a Day-5
      cut-off value >=2, the 'modified Palraj's score' showed sensitivities of 42.1%
      and 97.0% and specificities of 88.6% and 32.0% for Day-1 and Day-5 scores,
      respectively. CONCLUSION: We modify and expand upon an effective scoring system
      to identify SAB patients at high risk for endocarditis in order to guide use of
      TEE. The inclusion of IVDA in the criteria for the calculation of the scores
      improves its effectiveness.

PMID- 29064262
TI  - Prognostic comparison between creatinine-based glomerular filtration rate
      formulas for the prediction of 10-year outcome in patients with non-ST elevation
      acute coronary syndrome treated by percutaneous coronary intervention.
AB  - BACKGROUND:: Estimated glomerular filtration rate (eGFR) is a predictor of
      outcome among patients with non-ST-elevation acute coronary syndrome (NSTE-ACS),
      but which estimation formula provides the best long-term risk stratification in
      this setting is still unclear. We compared the prognostic performance of four
      creatinine-based formulas for the prediction of 10-year outcome in a NSTE-ACS
      population treated by percutaneous coronary intervention. METHODS:: In 222 NSTE
      ACS patients submitted to percutaneous coronary intervention, eGFR was calculated
      using four formulas: Cockcroft-Gault, re-expressed modification of diet in renal
      disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-Epi), and
      Mayo-quadratic. Predefined endpoints were all-cause death and a composite of
      cardiovascular death, non-fatal reinfarction, clinically driven repeat
      revascularisation, and heart failure hospitalisation. RESULTS:: The different
      eGFR values showed poor agreement, with prevalences of renal dysfunction ranging
      from 14% to 35%. Over a median follow-up of 10.2 years, eGFR calculated by the
      CKD-Epi and Mayo-quadratic formulas independently predicted outcome, with an
      increase in the risk of death and events by up to 17% and 11%, respectively, for
      each decrement of 10 ml/min/1.73 m2. The Cockcroft-Gault and MDRD equations
      showed a borderline association with mortality and did not predict events. When
      compared in terms of goodness of fit, discrimination and calibration, the Mayo
      quadratic outperformed the other formulas for the prediction of death and the CKD
      Epi showed the best performance for the prediction of events (net
      reclassification improvement values 0.33-0.35). CONCLUSIONS:: eGFR is an
      independent predictor of long-term outcome in patients with NSTE-ACS treated by
      percutaneous coronary intervention. The Mayo-quadratic and CKD-Epi equations
      might be superior to classic eGFR formulas for risk stratification in these
      patients.

PMID- 29064263
TI  - Long-term prognostic value of delirium in elderly patients with acute cardiac
      diseases admitted to two cardiac intensive care units: a prospective study
      (DELIRIUM CORDIS).
AB  - BACKGROUND: Delirium is a frequent in-hospital complication in elderly patients,
      and is associated with poor clinical outcome. Its clinical impact, however, has
      not yet been fully addressed in the setting of the cardiac intensive care unit
      (CICU). The present study is a prospective, two-centre registry aimed at
      assessing the incidence, prevalence and significance of delirium in elderly
      patients with acute cardiac diseases. METHODS: Between January 2014 and March
      2015, all consecutive patients aged 65 years or older admitted to the CICU of our
      institutions were enrolled and followed for 6 months. Delirium was defined
      according to the confusion assessment method. RESULTS: During the study period,
      726 patients were screened for delirium. The mean age was 79.1+/-7.8 years. A
      total of 111 individuals (15.3%) were diagnosed with delirium; of them, 46
      (41.4%) showed prevalent delirium (PD), while 65 (58.6%) developed incident
      delirium (ID). Patients 85 years or older showed a delirium rate of 52.3%.
      Hospital stay was longer in delirious versus non-delirious patients. Patients
      with delirium showed higher in-hospital, 30-day and 6-month mortality compared to
      non-delirious patients, irrespective of the onset time (overall, ID or PD). Six
      month re-hospitalisation was significantly higher in overall delirium and the PD
      group, as compared to non-delirious patients. Kaplan-Meier analysis showed a
      significant reduction of 6-month survival in patients with delirium compared to
      those without, irrespective of delirium onset time (i.e. ID or PD). A positive
      confusion assessment method was an independent predictor of short and long-term
      mortality. CONCLUSIONS: Delirium is a common complication in elderly CICU
      patients, and is associated with a longer and more complicated hospital stay and
      increased short and long-term mortality. Our findings suggest the usefulness of a
      protocol for the early identification of delirium in the CICU.
      Clinicaltrials.gov: NCT02004665.

PMID- 29064264
TI  - Accuracy of Models to Identify Lung Nodule Cancer Risk in the National Lung
      Screening Trial.

PMID- 29064260
TI  - Deterioration of Limb Muscle Function during Acute Exacerbation of Chronic
      Obstructive Pulmonary Disease.
AB  - Important features of both stable and acute exacerbation of chronic obstructive
      pulmonary disease (COPD) are skeletal muscle weakness and wasting. Limb muscle
      dysfunction during an exacerbation has been linked to various adverse outcomes,
      including prolonged hospitalization, readmission, and mortality. The contributing
      factors leading to muscle dysfunction are similar to those seen in stable COPD:
      disuse, nutrition/energy balance, hypercapnia, hypoxemia, electrolyte
      derangements, inflammation, and drugs (i.e., glucocorticoids). These factors may
      be the trigger for a downstream cascade of local inflammatory changes, pathway
      process alterations, and structural degradation. Ultimately, the clinical effects
      can be wide ranging and include reduced limb muscle strength. Current therapies,
      such as pulmonary/physical rehabilitation, have limited impact because of low
      participation rates. Recently, novel drugs have been developed in similar
      disorders, and learnings from these studies can be used as a foundation to
      facilitate discovery in patients hospitalized with a COPD exacerbation.
      Nevertheless, investigators should approach this patient population with
      knowledge of the limitations of each intervention. In this Concise Clinical
      Review, we provide an overview of acute muscle dysfunction in patients
      hospitalized with acute exacerbation of COPD and a strategic approach to drug
      development in this setting.

PMID- 29064265
TI  - Pregnancy Complications and Wheezing and Asthma in Childhood.

PMID- 29064266
TI  - Outcome after cardiopulmonary resuscitation in patients with congenital heart
      disease.
AB  - BACKGROUND: Outcome after cardiopulmonary resuscitation (CPR) in patients with
      underlying congenital heart disease is uncertain. This study aimed at evaluating
      outcome after CPR in patients with underlying congenital heart disease, factors
      related to worse outcome after CPR and whether survivors of sudden cardiac death
      (SCD) have a worse outcome when compared to an age, gender and disease-matched
      control population. METHODS: Between 1984 and 2015, all patients with congenital
      heart disease who received in or out-of-hospital CPR were identified from the
      database of congenital heart disease from the University Hospitals Leuven.
      Postoperative and neonatal (<6 months of age) CPR was excluded. For each survivor
      of SCD, two control patients matched for gender, age and underlying heart defect
      were included in the study. RESULTS: Thirty-eight patients (66% men; median age
      25 years (interquartile range 9-40); 68% out-of-hospital) were identified, of
      which 27 (66%) survived the event. The main cause of SCD was ventricular
      tachycardia or fibrillation ( n=21). Heart defect complexity (odds ratio (OR)
      5.1; 95% confidence interval (CI) 1.2-21.9; P=0.027), pulmonary hypertension (OR
      13.8; 95% CI 2.1-89.5; P=0.006) and time to return of spontaneous circulation (OR
      1.1; 95% CI 1.0-1.1; P=0.046) were related to worse outcome. Survivors of SCD had
      a worse prognosis when compared to an age, gender and disease-matched control
      group (5-year survival 76% vs. 98%; P=0.002). CONCLUSIONS: The complexity of
      underlying heart defect, pulmonary hypertension and time to return of spontaneous
      circulation are related to worse outcome in the case of CPR. Survivors of SCD
      have a worse outcome when compared to matched controls, indicating the need for
      adequate implantable cardioverter defibrillator indication assessment and for
      stringent follow-up of patients with worsening haemodynamics.

PMID- 29064267
TI  - Frailty and acute coronary syndrome: A structured literature review.
AB  - The health burden of acute coronary syndrome (ACS) and frailty is high, but the
      impact of frailty on ACS treatment and outcomes is uncertain. In this structured
      literature review, we investigated the relationship between frailty, ACS
      treatment and outcomes. Between 2000 and 2016, we identified only a small number
      of primary research studies investigating frailty and ACS care ( n = 10). Frailty
      was independently associated with increased mortality following ACS (adjusted all
      cause mortality hazard ratios for patients with frailty ranged from 1.54 to
      5.39). Older people with frailty were significantly less likely to receive
      guideline-indicated ACS care, including percutaneous coronary intervention (PCI)
      (rates ranged from 6.7% to 43.7% vs. from 30.4% to 69.5%). Available data for PCI
      indicated a gap between treatment recommended by international guidelines and
      clinical practice. Further research is warranted in order to investigate methods
      for identifying frailty in the acute setting and opportunities for improving care
      among older people with frailty presenting with ACS.

PMID- 29064268
TI  - Swyer-James Syndrome.

PMID- 29064269
TI  - Complement activation products in acute heart failure: Potential role in
      pathophysiology, responses to treatment and impacts on long-term survival.
AB  - BACKGROUND: Previous studies have indicated a correlation between heart failure,
      inflammation and poorer outcome. However, the pathogenesis and role of
      inflammation in acute heart failure (AHF) is incompletely studied and understood.
      The aim of our study was to explore the potential role of innate immunity -
      quantified by complement activation products (CAPs) - in pathophysiology,
      responses to treatment and impacts on long-term survival in AHF. METHODS: In a
      prospective study enrolling 179 unselected patients with AHF, plasma
      concentrations of C4d, C3a and sC5b-9 were measured in a blinded fashion on the
      first day of hospitalisation and prior to discharge. The final diagnosis,
      including the AHF phenotype, was adjudicated by two independent cardiologists.
      Long-term follow-up was obtained. Findings in AHF were compared to that obtained
      in 75 healthy blood donors (control group). RESULTS: Overall, concentrations of
      all three CAPs were significantly higher in patients with AHF than in healthy
      controls (all p < 0.001). In an age-adjusted subgroup analysis, significant
      differences could be confirmed for concentrations of C4d and sC5b-9, and these
      parameters further increased after 6 days of in-hospital treatment ( p < 0.001).
      In contrast, C3a levels in AHF patients did not differ from those of the control
      group in the age-adjusted subgroup analysis and remained constant during
      hospitalisation. Concentrations of C4d, C3a and sC5b-9 were significantly higher
      when AHF was triggered by an infection as compared to other triggers ( p <
      0.001). In addition, CAP levels significantly correlated with each other ( r =
      0.64-0.76), but did not predict death within 2 years. CONCLUSIONS: Activation of
      complement with increased plasma levels of C4d and sC5b-9 at admission and
      increasing levels during AHF treatment seems to be associated with AHF,
      particularly when AHF was triggered by an infection. However, CAPs do not have a
      prognostic value in AHF.

PMID- 29064270
TI  - Women have a worse prognosis and undergo fewer coronary angiographies after out
      of-hospital cardiac arrest than men.
AB  - BACKGROUND: Out-of-hospital cardiac arrest is more often reported in men than in
      women. OBJECTIVES: We aimed to assess sex-related differences in post
      resuscitation care; especially with regards to coronary angiography, percutaneous
      coronary intervention, mortality and functional status after out-of-hospital
      cardiac arrest. METHODS: We included 704 consecutive adult out-of-hospital
      cardiac arrest-patients with cardiac aetiology in the Copenhagen area from 2007
      2011. Utstein guidelines were used for the pre-hospital data. Vital status and
      pre-arrest comorbidities were acquired from Danish registries and review of
      patient charts. Logistic regression was used to assess differences in functional
      status and use of post-resuscitation care. Cox regression was used to assess
      differences in 30-day mortality. We used 'smcfcs' and 'mice' imputation to handle
      missing data. RESULTS: Female sex was associated with higher 30-day mortality
      after adjusting for age and comorbidity (hazard ratio (HR): 1.42, confidence
      interval (CI): 1.13-1.79, p<0.01), this was not significant when adjusting for
      primary rhythm (HR: 1.12, CI: 0.88-1.42, p=0.37). Women less frequently received
      coronary angiography <24 h in multiple regression after out-of-hospital cardiac
      arrest (odds ratio (OR)CAG=0.55, CI: 0.31-0.97, p=0.041), however no difference
      in percutaneous coronary intervention was found (ORPCI=0.55, CI: 0.23-1.36,
      p=0.19). Coronary artery bypass grafting was less often performed in women
      (ORCABG: 0.10, CI: 0.01-0.78, p=0.03). There was no difference in functional
      status at discharge between men and women ( p=1). CONCLUSION: Female sex was not
      significantly associated with higher mortality when adjusting for confounders.
      Women less often underwent coronary angiography and coronary artery bypass
      grafting, but it is not clear whether this difference can be explained by other
      factors, or an actual under-treatment in women.

PMID- 29064271
TI  - Effects of extracorporeal cardiopulmonary resuscitation on neurological and
      cardiac outcome after ischaemic refractory cardiac arrest.
AB  - BACKGROUND: Extracorporeal cardiopulmonary resuscitation is increasingly
      recognised as a rescue therapy for refractory cardiac arrest, nevertheless data
      are scanty about its effects on neurologic and cardiac outcome. The aim of this
      study is to compare clinical outcome in patients with cardiac arrest of ischaemic
      origin (i.e. critical coronary plaque during angiography) and return of
      spontaneous circulation during conventional cardiopulmonary resuscitation vs
      refractory cardiac arrest patients needing extracorporeal cardiopulmonary
      resuscitation. Moreover, we tried to identify predictors of survival after
      successful cardiopulmonary resuscitation. METHODS: We enrolled 148 patients with
      ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared
      clinical characteristics, cardiac arrest features, neurological and
      echocardiographic data obtained after return of spontaneous circulation (within
      24 h, 15 days and six months). RESULTS: Patients in the extracorporeal
      cardiopulmonary resuscitation group ( n=63, 43%) were younger (59+/-9 vs 63+/-8
      year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those
      with conventional cardiopulmonary resuscitation. In the extracorporeal
      cardiopulmonary resuscitation group, left ventricular ejection fraction was lower
      than conventional cardiopulmonary resuscitation at early echocardiography (19+/
      16% vs 37+/-11 p<0.01). Survivors in both groups showed similar left ventricular
      ejection fraction 15 days and 4-6 months after cardiac arrest (46+/-8% vs 49+/
      10, 47+/-11% vs 45+/-13%, p not significant for both), despite a major extent and
      duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation
      patients. At multivariate analysis, the total cardiac arrest time was the only
      independent predictor of survival. CONCLUSIONS: Extracorporeal cardiopulmonary
      resuscitation patients are younger and have less comorbidities than conventional
      cardiopulmonary resuscitation, but they have worse survival and lower early left
      ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary
      resuscitation have a neurological outcome and recovery of heart function
      comparable to subjects with return of spontaneous circulation. Total cardiac
      arrest time is the only predictor of survival after cardiopulmonary resuscitation
      in both groups.

PMID- 29064272
TI  - Risk Factors Associated with Asthma Development and Control in Children. Mouse
      Infestation, Antipyretics, Respiratory Viruses, and Allergic Sensitization.

PMID- 29064273
TI  - Acculturation is associated with higher prevalence of cardiovascular disease risk
      factors among Chinese immigrants in Australia: Evidence from a large population
      based cohort.
AB  - Background Acculturation is associated with increased prevalence of
      cardiovascular disease (CVD) risk-factors among immigrants in Western countries.
      Little is known about acculturation effects on CVD risks among Chinese
      immigrants, one of the fastest growing populations in Western countries. In this
      study, we aim to examine the association between acculturation and CVD risk
      factors among Chinese immigrants, Australia's third-largest foreign-born group.
      Methods We accessed a subsample of Chinese immigrants ( n = 3220) within the 45
      and-Up Study (2006-2009). Poisson regression model with a robust error variance
      examined the association between acculturation and CVD risk-factors, and
      prevalence ratios were reported, adjusted for socio-demographic characteristics.
      Indicators of acculturation included age at migration, length of Australian
      residence and language spoken at home. The outcomes were self-reported CVD
      diagnosis and six risk-factors (hypertension, diabetes, high cholesterol,
      smoking, overweight/obesity, physical inactivity). Results Mean age of Chinese
      participants was 58.9-years (SD = 10.7) and 55.5% were women. Chinese migrating
      to Australia aged <18 years were significantly more likely to report diabetes
      (prevalence ratio = 1.71; p < 0.01), overweight/obesity (prevalence ratio = 1.49;
      p < 0.001) and >= 3 CVD risk-factors (prevalence ratio = 1.47; p < 0.05) compared
      with those who migrated after 18-years-old. Chinese immigrants who lived in
      Australia for >= 30 years were significantly more likely to have diabetes
      (prevalence ratio = 1.84; p < 0.01) and >= 3 CVD risk-factors (prevalence ratio =
      1.84; p < 0.01). There were no significant differences by language spoken at
      home. The association between indicators of acculturation and CVD risk-factors
      appeared to differ by sex. Conclusion Greater acculturation was associated with
      adverse CVD risk-factors among Chinese immigrants in Australia.

PMID- 29064274
TI  - Effects of birth weight on profiles of dried blood amino-acids and
      acylcarnitines.
AB  - Background Birth weight influences profiles of dried blood amino-acids and
      acylcarnitines in newborn screening. This study aimed to define a more
      appropriate cut-off value to reduce the false positive rate and the number of
      recalled patients in newborn screening. Methods All babies who underwent newborn
      screening in our center were included; they were divided into groups by birth
      weight: 2500-3999 g (comparator group), <1000 g (group 1), 1000-1499 g (group 2),
      1500-2499 g (group 3), and >4000 g (group 4). The 0.5th and 99.5th percentiles
      were used as the cut-off values. Comparisons were done on amino acid and
      acylcarnitines concentrations between the groups. False positive rate, positive
      predictive value, corrected false positive rate by birth weights were determined.
      Results Data on a total of 578,287 newborn infants were included in the analysis.
      The total false positive rate was 0.75%, and positive predictive value 2.89%. The
      false positive rate was 0.69%, 0.54% and 5.31% in infants with normal birth
      weight, birth weight of >4000 (group 4) and low birth weight of < 2500 g (groups
      1, 2 and 3), respectively. Low-birth weight infants had much higher
      phenylalanine, tyrosine, methionine, arginine, propionylcarnitine,
      isovalerylcarnitine and octadecanoylcarnitine concentrations. Free carnitines and
      palmitoylcarnitine concentrations were lower. After adjusting for birth weight,
      false positive rate of all indices decreased to 0.53%, and positive predictive
      value increased to 4.31%. Conclusions Amino acid and carnitine concentrations in
      low-birth weight newborn infants may differ from the normal term newborn infants.
      The cut-off values of individual metabolites should be adjusted based on birth
      weight, to reduce false positive rate and increase positive predictive value.

PMID- 29064275
TI  - Challenges in the Diagnosis and Management of Pediatric Hemophagocytic
      Lymphohistiocytosis.

PMID- 29064276
TI  - Predictors of acute kidney injury in patients admitted with ST-elevation
      myocardial infarction - results from the Bremen STEMI-Registry.
AB  - BACKGROUND:: Deterioration of renal function after exposition to contrast media
      is a common problem in patients with myocardial infarction undergoing
      percutaneous coronary interventions. The aim of the present study was to assess
      the incidence of acute kidney injury in patients admitted with ST-elevation
      myocardial infarction (STEMI) and its association with infarction severity,
      comorbidities and treatment modalities, including amount of contrast media
      applied. METHODS:: All patients with STEMI from the metropolitan area of Bremen,
      Germany are treated at the Bremen Heart Centre and since 2006 documented in the
      Bremen STEMI-Registry. Acute kidney injury was graded from stage 0 to 3 following
      the Kidney-disease-improving-global outcomes criteria from 2012. RESULTS:: Data
      from 3810 patients admitted with STEMI were included in this study. No acute
      kidney injury was observed in 3120 (82%) patients while acute kidney injury was
      detected in 690 (18%) patients: Stage 1: n=497 (13%), 2: n=66 (2%), 3: n=127
      (3%). Acute kidney injury was associated with elevated 30-day (0: 3%, 1: 20%, 2:
      46%, 3: 58%) and one-year mortality rates (0: 6%, 1: 26%, 2: 49%, 3: 66%). Higher
      acute kidney injury stages were associated with higher peak creatine kinase (in
      U/l+/-SEM): stage 0: 1748+/-33, 1: 2588+/-127, 2: 3684+/-395, 3: 3330+/-399, p
      (<0.01), lower mean systolic blood pressure at admission (in mmHG+/-SD): 0: 133+/
      28, 1: 129+/-31; 2: 121+/-31, 3: 115+/-33 ( p<0.01) and higher Thrombolysis in
      Myocardial Infarction risk score for STEMI (scale 0-14+/-SD): 0: 2.71+/-2, 1:
      4.08+/-2, 2: 4.98+/-2, 3: 5.05+/-2, ( p<0.01). However, no such association could
      be found between acute kidney injury stage and amount of contrast media applied
      (in ml+/-SD) 0: 138+/-57, 1: 139+/-61; 2: 140+/-76; 3: 145+/-80 ( p=0.5). Reduced
      initial glomerular filtration rate was associated with higher incidences of acute
      kidney injury while again no relation to amount of contrast media could be
      observed in subgroups ranked by initial glomerular filtration rate. A
      multivariate analysis confirmed these results: while left-heart
      failure/cardiogenic shock (odds ratio (OR) 4.2, 95% confidence interval (CI) 3.3
      5.5) as well as larger infarctions (peak creatine kinase >3000 U/l (OR 2.2, 95%
      CI 1.7-2.8)) were independently associated with a greater risk for acute kidney
      injury, amount of contrast media applied during angiography was not (150-250 ml,
      OR 0.95, 95% CI 0.8-1.2 ( p=0.7), >250 ml, OR 1.3, 95% CI 0.8-2.0 ( p=0.5)).
      CONCLUSIONS:: Acute kidney injury, which was associated with elevated short- and
      long-term mortality rates, could be observed in 18% of patients admitted with
      STEMI. The present data suggest that severity and haemodynamic impairment due to
      STEMI rather than contrast-media-induced nephropathy is the key contributor for
      acute kidney injury in STEMI patients. The deleterious effect of the myocardial
      infarction itself on renal function can be explained through renal hypoperfusion,
      neurohormonal activation or other pathomechanisms that might have been
      underestimated in the past.

PMID- 29064278
TI  - Marijuana/Cannabis Use and Breastfeeding: A Clinical Dilemma.

PMID- 29064277
TI  - High sensitivity cardiac troponins: Can they help in diagnosing myocardial
      ischaemia?
AB  - BACKGROUND: Cardiac troponin is the most sensitive marker of myocardial injury,
      but controversy still exists about its role in detecting ischaemia. METHODS: To
      investigate the role of troponin as a marker of stress-induced ischaemia,
      circulating high sensitivity cardiac troponin T (hs-cTnT) was measured and
      compared with the MB fraction of creatine kinase (CK-MB) in 125 patients
      undergoing a stress test (53 electrocardiogram/echo exercise, 42 echo
      dipyridamole and 30 echo dobutamine tests). RESULTS: Plasma concentrations of hs
      cTnT increased after the tests in 90/125 patients, while an increase of CK-MB was
      seen in 31/125 patients ( p<0.0001). Overall, hs-cTnT significantly increased
      from 17.5+/-16.9 ng/l to 25.5+/-27.9 ng/l ( p<0.0001), without significant
      changes of CK-MB. Significant increments in hs-cTnT were documented after
      exercise test (from 15.9+/-11.9 ng/l to 19.5+/-13.6 ng/l, p<0.0001) and
      dobutamine test (from 20.6+/-20.8 ng/l to 37.8+/-31.1 ng/l, p=0.0006), in absence
      of changes in CK-MB according to each stressor. Among the 125 tests, 84 were
      diagnosed as negative and 41 as positive for myocardial ischaemia. Significant
      increments in hs-cTnT were detected after both negative (from 18.6+/-19.2 ng/l to
      27.1+/-32.1 ng/l, p=0.0018) and positive test (from 15.2+/-10.8 ng/l to 22.3+/
      16.2 ng/l, p=0.0005), without significant changes of CK-MB according to the test
      result. Despite a positive correlation between stress-induced increase of hs-cTnT
      and obstructive coronary artery disease, the release of troponin was observed
      also in a significant proportion of patients without coronary stenoses. Left
      ventricular hypertrophy markedly enhanced myocardial release of troponin.
      CONCLUSIONS: Circulating troponin increases in most patients undergoing a stress
      test, irrespective of the test result and of coronary artery disease. Plasma
      release of troponin depends on multiple pathogenetic mechanisms, making the
      biomarker a not reliable tool in detecting transient ischaemia.

PMID- 29064279
TI  - The Effect of Yoga on Arm Volume, Strength, and Range of Motion in Women at Risk
      for Breast Cancer-Related Lymphedema.
AB  - OBJECTIVES: To assess the feasibility, safety, and initial estimates of efficacy
      of a yoga program in postoperative care for women at high risk for breast cancer
      related lymphedema (BCRL). DESIGN: Single-group pretest-post-test design.
      SETTINGS/LOCATION: Patients were recruited from the University of California, San
      Francisco Carol Franc Buck Breast Care Center. SUBJECTS: Twenty-one women were
      enrolled in the study. Women were >18 years of age, had undergone surgical
      treatment for breast cancer, and were at high risk for BCRL. INTERVENTION: The
      women participated in an Ashtanga yoga intervention for 8 weeks. Sessions
      consisted of once/week instructor-led practice and once/week home practice.
      Particular attention was given to poses that emphasized upper body strength and
      flexibility, while avoiding significant time with the upper extremity (UE) in a
      dependent position. OUTCOME MEASURES: UE volume was assessed through
      circumferential forearm measurement, which was converted to volume using the
      formula for a truncated cone. Range of motion (ROM) was assessed for the
      shoulders, elbows, and wrists, using a standard goniometer. UE strength was
      assessed for shoulder abduction, elbow flexion, wrist flexion, and grip using a
      dynamometer. RESULTS: Twenty women completed the yoga intervention, with 17
      returning for final assessment. Mean age was 52 (+/-9.1) years and body mass
      index was 24.8 (+/-5.1) kg/m2. Postintervention, mean volume in the at-risk UE
      was slightly reduced (p = 0.397). ROM for shoulder flexion (p < 0.01) and
      external rotation (p < 0.05) significantly increased bilaterally. Shoulder
      abduction ROM significantly improved for the unaffected limb (p = 0.001).
      Following intervention, strength improved on the affected side for shoulder
      abduction and grip strength, and bilaterally for elbow flexion (p < 0.05 for
      all). CONCLUSIONS: These preliminary findings suggest that yoga is feasible and
      safe for women who are at risk for BCRL and may result in small improvements in
      shoulder ROM and UE strength.

PMID- 29064280
TI  - Prevalence and Trends in Donor Milk Use in the Well-Baby Nursery: A Survey of
      Northeast United States Birth Hospitals.
AB  - BACKGROUND AND OBJECTIVES: Pasteurized donor human milk ("donor milk") is an
      alternative to formula for supplementation of breastfed infants. We conducted a
      survey to determine (1) prevalence, trends, and hospital-level correlates of
      donor milk use for healthy newborns in the northeast United States and (2)
      clinician knowledge and opinions regarding this practice. METHODS: We conducted
      parallel surveys of clinicians (88% nurse and/or lactation consultant) at (1) all
      birth hospitals in Massachusetts (MA) and (2) all birth hospitals served by a
      northeast United States milk bank. We asked about hospital use of donor milk for
      newborns >=35 weeks' gestation and receiving Level I care in well nursery,
      hospital-related factors we hypothesized would be associated with this practice,
      and clinician knowledge and opinions about donor milk use. RESULTS: 35/46 (76%)
      of MA birth hospitals and 51/69 (74%) of hospitals served by the milk bank
      responded; 71 unique hospitals were included. Twenty-nine percent of MA birth
      hospitals and 43% of hospitals served by the milk bank reported using donor milk
      for healthy newborns. Hospitals that used donor milk for healthy newborns had
      higher exclusive breastfeeding at hospital discharge than hospitals that did not
      (77% versus 56%, p = 0.02). Eighty-three percent of respondents agreed or
      strongly agreed that using donor milk is an effective way to increase the
      hospital's exclusive breastfeeding rate. CONCLUSIONS: Many northeast United
      States birth hospitals currently use donor milk for healthy newborns. This
      practice is associated with higher exclusive breastfeeding at hospital discharge.
      Relationships with breastfeeding after discharge and related outcomes are
      unknown.

PMID- 29064282
TI  - Cannabis and Breastfeeding.

PMID- 29064283
TI  - Treating anxiety and depression in young adults: A randomised controlled trial
      comparing clinician-guided versus self-guided Internet-delivered cognitive
      behavioural therapy.
AB  - BACKGROUND: Internet-delivered cognitive behaviour therapy may increase access by
      young adults to evidence-based treatments for anxiety and depression. OBJECTIVE:
      The aim of this study was to compare the efficacy of an Internet-delivered
      cognitive behaviour therapy intervention designed for adults aged 18-24 years,
      when delivered in clinician-guided versus self-guided formats. DESIGN: The
      intervention, the Mood Mechanic Course, is a transdiagnostic treatment that
      simultaneously targets symptoms of anxiety and depression using cognitive and
      behavioural skills. The brief intervention comprised four lessons, delivered over
      5 weeks. Following a brief telephone interview, young adults ( n = 191) with
      symptoms of anxiety and depression were randomly allocated to either (1)
      clinician-guided treatment ( n = 96) or (2) self-guided treatment ( n = 95).
      RESULTS: At post treatment, large reductions (average improvement; clinician
      guided vs self-guided) were observed in symptoms of anxiety (44% vs 35%) and
      depression (40% vs 31%) in both groups. Significant improvements were also
      observed in general psychological distress (33% vs 29%), satisfaction with life
      (18% vs 15%) and disability (36% vs 29%). No marked or consistent differences in
      clinical outcomes emerged between conditions at post-treatment, at 3-month or 12
      month follow-up. Satisfaction was high with both treatment formats, but slightly
      higher for clinician-guided treatment. CONCLUSION: These results indicate the
      potential of carefully developed Internet-delivered cognitive behaviour therapy
      interventions for young adults with anxiety and depression provided in either
      self or therapist-guided format. Further large-scale research is required to
      determine the short- and long-term advantages and disadvantages of different
      models of support.

PMID- 29064281
TI  - IFN-stimulated Gene Expression, Type 2 Inflammation, and Endoplasmic Reticulum
      Stress in Asthma.
AB  - RATIONALE: Quantification of type 2 inflammation provided a molecular basis for
      heterogeneity in asthma. Non-type 2 pathways that contribute to asthma
      pathogenesis are not well understood. OBJECTIVES: To identify dysregulated
      pathways beyond type 2 inflammation. METHODS: We applied RNA sequencing to airway
      epithelial brushings obtained from subjects with stable mild asthma not on
      corticosteroids (n = 19) and healthy control subjects (n = 16). Sequencing reads
      were mapped to human and viral genomes. In the same cohort, and in a separate
      group with severe asthma (n = 301), we profiled blood gene expression with
      microarrays. MEASUREMENTS AND MAIN RESULTS: In airway brushings from mild asthma
      on inhaled corticosteroids, RNA sequencing yielded 1,379 differentially expressed
      genes (false discovery rate < 0.01). Pathway analysis revealed increased
      expression of type 2 markers, IFN-stimulated genes (ISGs), and endoplasmic
      reticulum (ER) stress-related genes. Airway epithelial ISG expression was not
      associated with type 2 inflammation in asthma or with viral transcripts but was
      associated with reduced lung function by FEV1 (rho = -0.72; P = 0.0004). ER
      stress was confirmed by an increase in XBP1 (X-box binding protein 1) splicing in
      mild asthma and was associated with both type 2 inflammation and ISG expression.
      ISGs were also the most activated genes in blood cells in asthma and were
      correlated with airway ISG expression (rho = 0.55; P = 0.030). High blood ISG
      expression in severe asthma was similarly unrelated to type 2 inflammation.
      CONCLUSIONS: ISG activation is prominent in asthma, independent of viral
      transcripts, orthogonal to type 2 inflammation, and associated with distinct
      clinical features. ER stress is associated with both type 2 inflammation and ISG
      expression.

PMID- 29064284
TI  - Pacing in age group marathoners in the "New York City Marathon".
AB  - The aim of the study was to investigate how women and men age group runners pace
      during a large city marathon. We analysed changes in running speed by splits of 5
      km in 20,283 women and 28,282 men age group runners competing in the 2015 edition
      of the "New York City Marathon". A moderate split*sex interaction on running
      speed (p < 0.001, eta2 = 0.108) was observed with men showing a larger decrease
      in speed from the fastest split (5-10 km) to the slowest one (35-40 km) than
      women (21.1 vs. 16.7%), and a different pattern was observed in the 25-30 km
      split (increase in women, decrease in men). A trivial split*age group interaction
      on speed was observed in women (p < 0.001, eta2 = 0.003) and men (p < 0.001, eta2
      = 0.004). In summary, men and women of all age groups reduced running speed
      during the marathon with a final spurt in the last segment (i.e. 40-42.2 km).

PMID- 29064285
TI  - The combined effects of on-road and simulator training with feedback on older
      drivers' on-road performance: Evidence from a randomized controlled trial.
AB  - OBJECTIVE: A number of training programs that seek to improve driving performance
      among older drivers are available accompanied by a growing interest in their
      effectiveness. The purpose of the present investigation was to examine the
      combined effect of (1) basic in-class training (BT); (2) on-road training with
      individualized feedback (OR); and (3) training on a driving simulator (S).
      METHODS: Using a randomized controlled trial study design, 78 older drivers were
      randomly assigned to one of 3 groups (BT, BT + OR, or BT + OR + S). All
      participants completed a pre- and postintervention on-road driving evaluation on
      a standardized route. The driving evaluations were recorded using video and
      Global Positioning System (GPS) equipment and were scored by a blind assessor.
      RESULTS: The results indicated a significant reduction of approximately 30% in
      overall number of driving errors/omissions among participants in the BT + OR and
      the BT + OR + S groups in comparison to participants in the BT group.
      CONCLUSIONS: This study adds to the mounting evidence demonstrating the
      effectiveness of individualized driver training in improving safe driving among
      older adults.

PMID- 29064287
TI  - Aerodynamic evaluation of the empty nose syndrome by means of computational fluid
      dynamics.
AB  - The potential outcome of a surgical enlargement of internal nasal channels may be
      a complication of nasal breathing termed the Empty Nose Syndrome (ENS). ENS
      pathophysiology is not entirely understood because the expansion of air pathways
      would in theory ease inhalation. The present contribution is aimed at defining
      the biophysical markers responsible for ENS. Our study, conducted in silico,
      compares nasal aerodynamics in pre- and post-operative geometries acquired by
      means of computer tomography from the same individual. In this article, we
      elucidate and analyse the deviation of airflow patterns and nasal microclimate
      from the healthy benchmarks. The analysis reveals 53% reduction in flow
      resistance, radical re-distribution of nasal airflow, as well as dryer and colder
      nasal microclimate for the post-operative case.

PMID- 29064286
TI  - Spontaneous coronary artery dissection, challenges of diagnosis and management.
AB  - Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause
      of acute coronary syndrome in young patients. No clear factors exist to predict
      the natural history of the disease and the prognosis of the condition.
      Furthermore, current management practice of SCAD is based mainly on retrospective
      data and case series and clear management guidelines are lacking. In this
      article, we present a series of cases of patients with SCAD and we will discuss
      the different clinical presentations, the diagnostic approaches and the options
      of management of this cohort of patients. Our aim is to outline the challenges of
      diagnosis and management of this interesting and serious pathology.

PMID- 29064289
TI  - The paradox of compassionate work: a mixed-methods study of satisfying and
      fatiguing experiences of animal health care providers.
AB  - BACKGROUND AND OBJECTIVES: Compassionate work appears paradoxical as it may
      provide great rewards, but may also come at great costs to care providers. This
      paper explores the paradox of compassionate work by examining what interactions
      contribute to compassion satisfaction and what interactions contribute to
      compassion fatigue. DESIGN: This mixed-methods, cross-sectional study uses
      qualitative interview data from animal health care providers (N = 20) to identify
      work interactions that they find satisfying or stressful. Quantitative survey
      data (N = 572) are used to test hypotheses generated from the interviews
      regarding predictors of compassion satisfaction and compassion fatigue. METHODS:
      Interview transcripts were analyzed using a directed content analysis approach.
      Survey data were analyzed using ordinary least squares regression. RESULTS: The
      results highlight the complex nature of compassionate work. As hypothesized,
      making a difference to animals and building relationships with animal patients
      and human clients relate to greater compassion satisfaction. Human client
      barriers to animal care and witnessing client grief relate to greater compassion
      fatigue, as predicted. None of the predictors relate to less compassion fatigue,
      but forming relationships with animal patients relates to both greater compassion
      satisfaction and compassion fatigue. CONCLUSIONS: This paper enhances our
      understanding of provider-client-patient interactions and highlights the paradox
      of compassionate work.

PMID- 29064288
TI  - Traumatic brain injury, psychiatric diagnoses, and suicide risk among Veterans
      seeking services related to homelessness.
AB  - OBJECTIVES: To explore the differences in negative psychiatric outcomes (i.e.
      type and number of psychiatric diagnoses, suicide risk) among Veterans with and
      without a history of traumatic brain injury (TBI) seeking homeless services.
      METHODS: Observational design with data collected at one time-point. Veterans
      seeking homeless services from two Veteran Affairs (VA) Medical Centres completed
      study measures (n = 309; 282 with a history of TBI and 27 without a history of
      TBI). Veterans participated in structured clinical interviews regarding
      psychiatric and TBI histories. RESULTS: Those with a history of TBI met the
      criteria for significantly more psychiatric diagnoses (p = 0.0003), and were more
      likely to be at risk for suicide (p = 0.007) than those without a history of TBI.
      CONCLUSIONS: Even among the high-risk cohort of homeless Veterans, those with a
      history of TBI were found to be at even greater risk for negative psychiatric
      outcomes. Further research is required to determine if and how the history of TBI
      contributes to the inability to maintain stable housing. Moreover, the findings
      highlight both the importance of assessing for history of TBI among this cohort,
      and educating providers regarding how to address the needs related to injury
      sequelae.

PMID- 29064291
TI  - Red beet and betaine as ingredients in diets of rainbow trout (Oncorhynchus
      mykiss): effects on growth performance, nutrient retention and flesh quality.
AB  - The objective of the study was to evaluate the impact of different concentrations
      of dietary red beet and betaine on the growth performance and fish flesh quality
      of rainbow trout. Therefore, a control diet was compared with four diets in which
      two levels of red beet (14% and 28%) and betaine (0.9% and 1.63%) were
      incorporated in combination. The study was set up with an average body weight of
      69 +/- 2.2 g and finished when fish reached commercial weight (175-250 g) after
      105 d. The impact of the diets was studied based on the growth performance,
      biometric indexes, proximal composition, protein and fat retention efficiencies
      and apparent nutrient digestibility by fish reared on a recirculation system.
      Further estimates were the effect of red beet and betaine on the flesh proximate
      composition and quality of the final product (water activity, colour, texture,
      thiobarbituric acid reactive substances and sensory characteristics). Results
      showed that inclusion of 14% red beet and 0.9% betaine did not affect growth,
      nutritive or biometric parameters and nutrient retention when compared with the
      control diet. However, higher levels of red beet and betaine had negative effects
      on growth and nutritive parameters. The tested ingredients enhanced quality
      parameters regardless of the concentration used. After feeding the red beet and
      betaine, fish flesh showed lower water activity and better textural and colour
      properties than the control and also a dose-dependent effect on lipid oxidation
      was observed.

PMID- 29064290
TI  - Quercetin/oleic acid-based G-protein-coupled receptor 40 ligands as new insulin
      secretion modulators.
AB  - AIM: Management of Type 2 diabetes mellitus by diet is achievable at the early
      stage of the disease; patients usually underestimate this approach and an
      appropriate drug therapy is required. RESULTS: Starting from quercetin and oleic
      acid, that have effect on insulin secretion, a small set of hybrid molecules was
      synthesized. Insulin secretion was evaluated in both in vitro and ex vivo models.
      AV1  was able to enhance insulin secretion dose dependently, behaving as a
      conceivable agonist of G-protein-coupled receptor 40. CONCLUSION: AV1 represents
      an interesting tool that interacts with G-protein-coupled receptor 40. Further
      studies will be carried out to evaluate the exact binding mode, and also to
      enlarge the library of these antidiabetic agents. [Formula: see text].

PMID- 29064292
TI  - Psychophysiological Response and Fine Motor Skills in High-Altitude Parachute
      Jumps.
AB  - Clemente-Suarez, Vicente Javier, Jose Juan Robles-Perez, Ketty Herrera-Mendoza,
      Belina Herrera-Tapias, and Jesus Fernandez-Lucas. Psychophysiological response
      and fine motor skills in high-altitude parachute jumps. High Alt Med Biol 18:392
      399, 2017.-We analyzed the psychophysiological response and specific fine motor
      skill of an experienced jumper in HALO (high altitude low opening) and HAHO (high
      altitude high opening) parachute jumps. Eight HALO and eight HAHO jumpers were
      analyzed. They jumped at 5500 m, HALO jumpers opened the parachute at 500 m and
      HAHO jumpers at 4300 m of altitude. Before and after the jumps, parameters of
      muscle strength, cortical arousal, blood creatine kinase (CK) and glucose, blood
      oxygen saturation, rate of perceived exertion (RPE), and specific fine motor
      skills of an experienced jumper were assessed; during the jump, heart rate (HR),
      HR variability, and speed were evaluated. HALO and HAHO jumps produced a
      significant increase in CK, lactate, and RPE, and a decrease in glucose. HAHO
      decreased cortical arousal, presented a higher sympathetic modulation, and a
      higher HR during the jump than HALO. HALO and HAHO produced an increase in the
      physiological, sympathetic modulation and muscle destruction, and a decrease in
      cortical arousal and a higher blood lactate concentration only in the HAHO jump.
      Also, somatic and cognitive anxiety correlated with higher strength manifestation
      and muscle destruction. This novel research could be used to improve actual
      training systems in both civil and military parachute jumpers.

PMID- 29064293
TI  - Transcatheter aortic valve implantation: where are we now?
AB  - Transcatheter aortic valve implantation (TAVI) was first used in clinical
      practice in 2002. Since 2002, there has been a rapid increase in TAVI activity in
      patients with symptomatic severe aortic stenosis. This has been supported by
      systematic randomized data comparing TAVI against the gold standard treatment for
      the last 50 years' surgical aortic valve replacement. TAVI is now currently a
      recommended therapeutic intervention in the treatment of severe aortic stenosis
      patients who are deemed either high risk or inoperable. The indications for TAVI
      continue to expand. Within this review we will focus on the current guidelines
      for TAVI, the evidence for it, the complications of TAVI, postprocedure care, the
      technology available to clinicians now and finally the future perspectives for
      TAVI.

PMID- 29064294
TI  - Voicing contrast of stop consonant production in the speech of individuals with
      Parkinson disease ON and OFF dopaminergic medication.
AB  - The aims of this study were to: 1) compare voicing contrast in speakers with
      Parkinson disease (PD) and healthy controls by comparing the separation of voice
      onset time (VOT) distributions of voiced and voiceless stop consonants and 2) to
      determine whether the administration of dopaminergic medication affected VOT
      separation in speakers with PD. Data from a previous study by Fisher and Goberman
      (2010) were used to compare the VOT measures obtained from a group of speakers
      with PD with both ON and OFF medication, and a group of healthy controls.
      Supplementing the previous findings, the current analysis revealed that
      individuals with PD exhibited significantly less contrast between voiced and
      voiceless VOT than that observed in healthy speakers. Medication administration
      did not affect VOT contrast as no differences in VOT separation were observed
      between the ON and OFF medication states.

PMID- 29064295
TI  - Vitamin D as a Therapeutic Option for Sunburn: Clinical and Biologic
      Implications.

PMID- 29064297
TI  - Updating the "Risk Index": A systematic review and meta-analysis of occupational
      injuries and work schedule characteristics.
AB  - Fatigue is a major risk factor for occupational 'accidents' and injuries, and
      involves dimensions of physical, mental, and muscular fatigue. These dimensions
      are largely influenced by temporal aspects of work schedules. The "Risk Index"
      combines four fatigue-related components of work schedules to estimate
      occupational 'accident' and injury risk based on empirical trends: shift type
      (morning, afternoon/evening, night), length and consecutive number, and on-shift
      rest breaks. Since its first introduction in 2004, several additional studies
      have been published that allow the opportunity to improve the internal and
      external validity of the "Risk Index". Thus, we updated the model's estimates by
      systematically reviewing the literature and synthesizing study results using meta
      analysis. Cochrane Collaboration directives and MOOSE guidelines were followed.
      We conducted systematic literature searches on each model component in Medline.
      An inverse variance approach to meta-analysis was used to synthesize study effect
      sizes and estimate between-studies variance ('heterogeneity'). Meta-regression
      models were conducted to explain the heterogeneity using several effect
      modifiers, including the sample age and sex ratio. Among 3,183 initially
      identified abstracts, after screening by two independent raters (95-98%
      agreement), 29 high-quality studies were included in the meta-analysis. The
      following trends were observed: Shift type. Compared to morning shifts, injury
      risk significantly increased on night shifts (RR = 1.36 [95%CI = 1.15-1.60], n =
      14 studies), while risk was slightly elevated on afternoon/evening shifts,
      although non-significantly (RR = 1.12 [0.76-1.64], n = 9 studies). Meta
      regressions revealed worker's age as a significant effect modifier: adolescent
      workers (<= 20 y) showed a decreased risk on the afternoon/evening shift compared
      to both morning shifts and adult workers (p < 0.05). Number of consecutive
      shifts. Compared to the first shift in a block of consecutive shifts, risk
      increased exponentially for morning shifts (e.g., 4th: RR = 1.09 [0.90-1.32]; n =
      6 studies) and night shifts (e.g., 4th: RR = 1.36 [1.14-1.62]; n = 8 studies),
      while risk on afternoon/evening shifts appeared unsystematic. Shift length.
      Injury risk rose substantially beyond the 9th hour on duty, a trend that was
      mirrored when looking at shift lengths (e.g., >12 h: RR = 1.34 [1.04-1.51], n = 3
      studies). Rest breaks. Risk decreased for any rest break duration (e.g., 31-60
      min: RR = 0.35 [0.29-0.43], n = 2 studies). With regards to time between breaks,
      risk increased with every additional half hour spent on the work task compared to
      the first 30 min (e.g., 90-119 min: RR = 1.62 [1.00-2.62], n = 3 studies). Rest
      break duration and interval seem to interact such that with increasing duration,
      the time between breaks becomes irrelevant. The updated "Risk Index". All four
      components were combined to form the updated model and the relative risk values
      estimated for a variety of work schedules. The resulting "Risk Map" shows regions
      of highest risk when rest breaks are not taken frequently enough (i.e. <4 h) or
      are too short (i.e. <30 min), when shift length exceeds 11 h, and when work takes
      place during the night (particularly for >3 consecutive night shifts). The "Risk
      Index" is proposed as an empirical model to predict occupational 'accident' and
      injury risk based on the most recent data in the field, and can serve as a tool
      to evaluate hazards and maximize safety across different work schedules.

PMID- 29064296
TI  - Tolerability and efficacy of colestipol hydrochloride for accelerated elimination
      of teriflunomide.
AB  - BACKGROUND: Teriflunomide is an oral disease modifying therapy approved for the
      treatment of relapsing forms of multiple sclerosis. Teriflunomide' s
      pharmacokinetics (PK) contribute to its slow elimination, on average taking 6-8
      months, though it can take up to 2 years in some instances. This slow elimination
      can become problematic in certain clinical situations - such as during pregnancy,
      when teriflunomide has potential teratogenic effects. In such scenarios, an
      accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral
      cholestyramine or activated charcoal are available but are restricted by adverse
      effects, limited administration routes, and dosing frequencies. METHODS: A single
      center, PK interaction study was performed in a total of 14 healthy volunteers,
      to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine
      for the elimination of teriflunomide. Participants received teriflunomide for 14
      days, followed by an AEP with colestipol HCl for 15 days. RESULTS AND
      CONCLUSIONS: The administration of colestipol HCl for 15 days was sufficient to
      reduce plasma teriflunomide concentrations by greater than 96%. Although
      colestipol HCl did not completely eliminate teriflunomide with the same
      effectiveness as cholestyramine, it may offer an alternative method for
      accelerated elimination of teriflunomide with potentially improved tolerability
      and more favorable dosing and administration options.

PMID- 29064299
TI  - Multilevel modeling of chronotype and weekdays versus weekends to predict
      nonrestorative sleep.
AB  - Nonrestorative sleep, a form of subjective sleep disturbance that has been
      largely neglected in the literature, is newly accessible to researchers via the
      validated restorative sleep questionnaire (RSQ). The daily version of the RSQ
      allows for analysis of within-subjects variation in restorative sleep across
      repeated samplings, and such day-to-day regularity in sleep variables has been
      highlighted as an important new direction for research. The present study used a
      sophisticated statistical approach, multilevel modeling, to examine the
      contributions of circadian chronotype, calendar day of questionnaire completion
      (weekends versus weekdays), and their interaction in explaining both
      interindividual and intraindividual variance in restorative sleep. Analyses were
      conducted using an archival dataset of college undergraduates who continuously
      completed daily RSQs over a 14-day sampling period. In the final multilevel
      model, possessing an evening type predicted lower restorative sleep between
      subjects, while sampling on weekdays predicted lower restorative sleep within
      subjects. Furthermore, a cross-level interaction was observed, such that the
      difference in restorative sleep on weekends versus weekdays was more pronounced
      among those with greater evening circadian preference. All of the effects were
      maintained after accounting for the significant influence of gender (women had
      less restorative sleep than men). These results are theoretically consistent with
      findings that evening types display stronger disparities in sleep schedules
      across free and workdays (i.e., social jet lag), and attest to the usefulness of
      multilevel models for statistically investigating how stable traits interact with
      factors that vary day to day (e.g., work or school schedules) in influencing
      sleep outcomes.

PMID- 29064298
TI  - Investigating Achilles and patellar tendinopathy prevalence in elite athletics.
AB  - Although injury surveillance in athletics is routinely conducted, discipline
      specific Achilles and patellar tendinopathy prevalence remains unknown. The
      purpose of this study was to explore discipline-specific tendinopathy prevalence
      and identify whether injury-specific risk factors differed in athletes. Elite
      athletes were recruited and provided information on their sport training
      including Achilles and patellar tendon pain history. In order to ascertain
      whether between-discipline differences existed, data were categorized into
      discipline groups. Middle-distance athletes reported the highest prevalence of
      Achilles tendinopathy and the combined athletes reported the highest patellar
      tendinopathy prevalence. Greater calf stiffness was reported in athletes who
      experienced Achilles tendinopathy compared to those who did not. A substantial
      portion of athletes believed their performance decreased as a result of their
      tendon pain. In order to develop discipline-specific evidence-based injury
      prevention programmes, further discipline-specific research is required to
      quantify the mechanism for Achilles and patellar tendinopathy development in
      elite athletics.

PMID- 29064300
TI  - Interdisciplinary eHealth for the care of people living with traumatic brain
      injury: A systematic review.
AB  - OBJECTIVE: To identify literature which discusses the barriers and enablers of
      eHealth technology and which evaluates its role in facilitating interdisciplinary
      team work for the care of people with a traumatic brain injury (TBI). DESIGN:
      Systematic review. DATA SOURCES: Studies were identified by searching CINAHL,
      Embase, Medline, PsycINFO, Scopus, and Web of Science. STUDY SELECTION: Studies
      included in the review were required to feature an eHealth intervention which
      assisted interdisciplinary care for people with TBI. DATA EXTRACTION: Descriptive
      data for each study described the eHealth intervention, interdisciplinary team,
      outcomes, and barriers and facilitators in implementing eHealth interventions.
      RESULTS: The search resulted in 1389 publications, of which 35 were retrieved and
      scanned in full. Six studies met all the inclusion criteria for the review. Four
      different eHealth interventions were identified: (i) an electronic goals systems,
      (ii) telerehabilitation, (iii) videoconferencing, and (iv) a point-of-care team
      based information system. Various barriers and facilitators were identified in
      the use of eHealth. CONCLUSION: eHealth interventions have been reported to
      support interdisciplinary teams for the care of TBI. However, there is a
      substantial gap in existing literature regarding the barriers and enablers which
      characterize a successful interdisciplinary eHealth model for people with TBI.

PMID- 29064302
TI  - Study of chest injuries to 3-year-old child occupants seated in impact shield and
      5-point harness CRSs.
AB  - OBJECTIVE: The objective of this study was to investigate whether the 5-point
      harness or the impact shield child restraint system (CRS) or both have the
      potential to cause chest injuries to children. This is determined by examining
      whether the loading to the chest reaches the internal organ injury threshold for
      children. METHOD: The chest injury risk to a child occupant in a CRS was
      investigated using Q3 dummy tests, finite element (FE) simulations (Q3 dummy and
      human models), and animal tests. The investigation was done for 2 types of CRSs
      (i.e., the impact shield CRS and 5-point harness CRS) based on the UN R44 dynamic
      test specifications. RESULTS: The tests using a Q3 dummy indicated that although
      the chest deflection of the dummy in the impact shield CRS was large, it was less
      than the injury threshold (40 mm). Computational biomechanics simulations (using
      finite element FE analysis) showed that the Q3 dummy's chest is loaded by the
      shield and deforms substantially under this load. To clarify whether chest
      injuries due to chest compression can occur with an impact shield or with the 5
      point harness CRS, 7 experiments were performed using Tibetan miniature pigs with
      weights ranging from 9.7 to 13 kg. Severe chest and abdominal injuries (lung
      contusion, coronary artery laceration, liver laceration) were found in the tests
      using the impact shield CRS. No chest injuries were present when using the 5
      point harness CRS. CONCLUSION: When using the impact shield CRS, the chest
      deformed substantially in dummy tests and FE simulations, and chest and abdominal
      injuries were observed in pig tests. It is possible that these chest injuries
      could also occur to child occupants sitting in the impact shield CRS.

PMID- 29064301
TI  - Association of waterpipe smoking with myocardial infarction and determinants of
      metabolic syndrome among catheterized patients.
AB  - BACKGROUND: Waterpipe smoking is a rising global public health epidemic perceived
      by many users to be less harmful, though its toxicity overlaps or even exceeds
      that of cigarette smoking. Short-term cardiovascular changes due to waterpipe
      smoking are well established, but longer-term health impacts are still not fully
      elucidated. OBJECTIVE: We aim to investigate the association of waterpipe smoking
      with myocardial infarction among patients undergoing cardiac catheterization.
      METHODS: The study was performed on Lebanese patients referred for cardiac
      catheterization. Patient's blood was collected for metabolic measures and
      questionnaires were filled out to include socio-demographic, behavioral and
      pertinent medical characteristics of the study subjects. RESULTS: Myocardial
      infarction is significantly and independently associated with waterpipe smoking,
      with odds ratio (OR) of 1.329 (95% CI: [1.04-1.68]; p = .021), which is lower
      than that for cigarette smoking (OR = 1.87, 95% CI: [1.63-2.15]; p < .001). Only
      diabetes showed significant association with waterpipe smoking among MI enrollees
      (OR = 1.66, 95%CI: [1.04-2.63]; p = .032). CONCLUSION: The study provides yet
      another evidence for the adverse cardiovascular effects of waterpipe smoking on a
      clinical level. The harmful effects of waterpipe smoking should be underscored by
      health care professionals.

PMID- 29064303
TI  - Daily rhythms of locomotor and demand-feeding activities in Schizothorax pelzami
      (Kessler, 1870).
AB  - A study was carried out to investigate the daily rhythms of locomotor and feeding
      activity of Khajoo, Schizothorax pelzami, a candidate species for freshwater
      aquaculture. Using self-feeder juvenile Khajoo were exposed to a 12/12 LD cycle
      to determine the rhythms of locomotor and feeding activity. The effects of
      feeding on locomotor and feeding activity of fish were also examined. Finally,
      the endogenous rhythmicity under different lighting condition tested. Fish
      displayed a strictly diurnal feeding and locomotor activities with 98% and 84% of
      the total activity occurred in the photophase, respectively. In scheduled
      feeding, both the L-group (fed in light) and the D-group (fed in the dark) showed
      a diurnal locomotor activity pattern. However, the L-group had a peak of
      locomotor activity near the feeding time, but the D-group had a scarce locomotor
      activity in the scatophase with no significant change at the mealtime. Most of
      the individuals display free-running rhythms when exposed to different lighting
      condition including, constant darkness, ultradian 45:45 min LD cycle and reversed
      DL photo cycle. Taken together the results of this study showed that both
      locomotor and feeding activity have diurnal rhythms in Khajoo S. pelzami, even
      fish feeding had taken place at night. Additionally, the free-running locomotor
      activity of the fish in the absence of external light stimuli, suggests the
      existence of an endogenous timing mechanism in this fish species.

PMID- 29064304
TI  - Introducing the model of cognitive-communication competence: A model to guide
      evidence-based communication interventions after brain injury.
AB  - PRIMARY OBJECTIVE: Communication impairments associated with acquired brain
      injury (ABI) are devastating in their impact on family, community, social,
      academic, and vocational participation. Despite international evidence-based
      guidelines for communication interventions, evidence practice gaps include under
      identification of communication deficits, infrequent referrals, and inadequate
      treatment to realize functional communication outcomes. Evidence-informed
      communication intervention requires synthesis of abundant interdisciplinary
      research. This study describes the development of the model of cognitive
      communication competence, a new model that summarizes a complex array of
      influences on communication to provide a holistic view of communication
      competence after ABI. RESEARCH DESIGN: A knowledge synthesis approach was
      employed to integrate interdisciplinary evidence relevant to communication
      competence. METHODS AND PROCEDURES: Development of the model included review of
      the incidence of communication impairments, practice guidelines, and factors
      relevant to communication competence guided by three key questions. This was
      followed by expert consultation with researchers, clinicians, and individuals
      with ABI. MAIN OUTCOMES AND RESULTS: The resulting model comprises 7 domains, 7
      competencies, and 47 factors related to communication functioning and
      intervention. CONCLUSION: This model could bridge evidence to practice by
      promoting a comprehensive and consistent view of communication competence for
      evidence synthesis, clinical decision-making, outcome measurement, and
      interprofessional collaboration.

PMID- 29064305
TI  - Maintaining the Momentum of Measuring What Matters: Overcoming Hurdles To Develop
      Electronic Clinical Quality Measures.

PMID- 29064306
TI  - Sex Differences in Patient-Reported Poststroke Disability.
AB  - BACKGROUND: Recent studies have shown that stroke has a differential impact in
      women compared to men. Women are more likely to survive strokes than men, yet
      they experience more severe strokes resulting in greater poststroke disability.
      However, few studies have characterized sex differences in functional ability
      after stroke. This study examined sex differences in long-term disability among
      stroke survivors. METHODS: This was a retrospective analysis of the 2015 National
      Health Interview Survey. Respondents were asked to rate their ability to perform
      11 functional tasks. Univariate comparisons were completed to evaluate sex
      differences in performance, and multinomial logistic regression was used to
      determine the odds of reporting functional limitations. RESULTS: Five hundred
      fourteen men and 641 women stroke survivors completed the survey (mean age: 66.9
      years). Approximately 75% of the sample reported having hypertension, 61% high
      cholesterol, 33% diabetes, 24% heart disease, 21% heart attack, and 16% chronic
      obstructive pulmonary disease. In the predictive models, men were less likely to
      report "very difficult/can't do at all" in walking 1/4 mile (odds ratios [OR] =
      0.68, 95% CI 0.51-0.90), climbing 10 steps (OR = 0.65, 95% CI 0.49-0.85),
      standing 2 hours (OR = 0.66, 95% CI 0.50-0.87), stooping (OR = 0.51, 95% CI 0.39
      0.68), reaching overhead (OR = 0.69, 95% CI 0.49-0.97), carrying 10 pounds (OR =
      0.45, 95% CI 0.34-0.59), and pushing large objects (OR = 0.37, 95% CI 0.28-0.5)
      compared to women. CONCLUSIONS: The functional outcomes of men stroke survivors
      were significantly greater than women. The specific factors that contribute to
      sex differences in stroke-related outcomes are not entirely clear. Future
      research is needed to better understand these differences to ensure that equity
      of care is received.

PMID- 29064307
TI  - Metabolomic Analysis and Antioxidant Effect of Amla (Emblica officinalis) Extract
      in Preventing Oxidative Stress-Induced Red Cell Damage and Plasma Protein
      Alterations: An In Vitro Study.
AB  - Amla (Emblica officinalis) has antidiabetic, hypolipidemic, anti-inflammatory,
      and antioxidant properties, but its effect on free radical induced red cell
      damage and membrane and plasma protein alterations has not been adequately
      addressed. The aim of the present study was to evaluate the antioxidant property
      of amla against oxidative stress-induced red cell damage and plasma protein
      alterations. Red blood cells (RBCs) were preincubated with different
      concentrations of amla extract (50, 100, 150, and 200 MUg/mL) and then treated
      with physiological (5 mM) and pathological (50 mM) concentrations of glucose for
      24 h. In another in vitro study the plasma was pretreated with different
      concentrations of amla extract and then incubated with 2, 2'-Azo-Bis (2
      methylpropionamidine) dihydrochloride (AAPH) for 2 h. After the incubation RBC
      malondialdehyde (MDA), RBC-reduced glutathione (GSH), RBC indices, RBC
      morphometric study, plasma MDA, protein carbonylation, total protein, and albumin
      were estimated. The antioxidant property of amla was assessed by DPPH assay. RBC
      MDA levels were significantly decreased and RBC-GSH levels were significantly
      increased with higher concentration of amla extract (150 and 200 MUg/mL). Red
      cell count and its indices were improved with the increasing concentration of
      amla. In addition, at higher concentration, amla restored the RBC membrane
      integrity. The plasma in vitro study also showed that amla improved the plasma
      MDA, protein carbonylation, total protein, and albumin levels. Amla extract
      effectively protected the RBCs and plasma proteins from the reactive oxygen
      species induced oxidative damage. Liquid chromatography-mass spectrometry (LC-MS)
      analysis of the extract revealed the presence of gallic acid, quinic acid, and
      quercetin as the major constituents in addition to the other flavonoids.

PMID- 29064308
TI  - Systematic Review of Drug-Induced Sleep Endoscopy Scoring Systems.
AB  - Objective To systematically review the scoring systems used to report findings
      during drug-induced sleep endoscopy (DISE) for adults and children with
      obstructive sleep apnea. Data Sources PubMed, CINAHL, EBM Reviews, Embase, and
      Scopus databases. Review Methods This is a systematic review of all indexed years
      of publications referring to scoring of DISE for children and adults with
      obstructive sleep apnea. The type of DISE scoring system utilized was the primary
      outcome. PRISMA guidelines were followed to carry out this review; articles were
      independently reviewed by 2 investigators. All pediatric and adult studies that
      utilized >=1 DISE grading systems were included. Results Of 492 identified
      abstracts, 44 articles (combined population, N = 5784) were ultimately included;
      6 reported on children, 35 on adults, and 1 on children and adults. Twenty-one
      reporting methods were used in these studies, with the most common being the VOTE
      system (velum, oropharynx, tongue base, and epiglottis; 38.6%) and the Pringle
      and Croft classification (15.9%). The sites of obstruction most commonly included
      in a scoring system were the tongue base (62%), lateral pharynx/oropharynx (57%),
      palate (57%), epiglottis/supraglottis (38%), and hypopharynx (38%). Less commonly
      included sites were the larynx (29%), velum (23%), nose (23%), tongue (14%),
      adenoids (10%), and nasopharynx (10%). Conclusion There is no consensus regarding
      which scoring system should be utilized to report findings during DISE. The VOTE
      system and the Pringle and Croft classification were the most frequent scoring
      systems reported for patients undergoing DISE. Standardization of the reporting
      of DISE findings would improve comparability among studies.

PMID- 29064309
TI  - Eyes on New Product Development.

PMID- 29064310
TI  - Hidden Blood Loss and Its Influential Factors After Laparoscopy-Assisted
      Gastrectomy for Gastric Cancer.
AB  - INTRODUCTION: Laparoscopy-assisted gastrectomy (LAG) is a minimally invasive
      procedure for the treatment of gastric cancer. It is generally thought that a
      minimally invasive technique results in less visible blood loss during the
      surgery. Nevertheless, a meaningful perioperative hidden blood loss (HBL) is
      often ignored. In this study, we investigated the amount of HBL and the
      influential factors after LAG for gastric cancer. METHODS: A retrospectively
      analyzed clinical data of 62 consecutive patients who underwent laparoscopy
      assisted total or distal gastrectomy at our center from May 2016 to May 2017. The
      HBL was calculated according to Gross's and Nadler's formula. The data of patient
      gender, age, height, weight, body mass index, preoperative and postoperative
      hematocrit, postoperative drainage, albumin loss, diabetes mellitus, and
      hypertension were analyzed by multivariate linear regression analysis. The type
      of surgical reconstruction was analyzed by one-way analysis of variance. The
      difference between the preoperative blood pressure and postoperative blood
      pressure was measured by paired sample t-test and boxplot. RESULTS: The HBL was
      322.2 +/- 195.9 mL (64.3% +/- 14.1% in total blood loss [TBL]), the TBL was 475.6
      +/- 222.8 mL, and the hemoglobin (HB) loss was 15.0 +/- 8.7 (11.5% +/- 6.1% of HB
      level loss). Multivariate linear regression analysis revealed that gender,
      hypertension, and albumin loss between preoperation and postoperation are
      influential factors of HBL in patients after LAG for gastric cancer. Compared to
      male patients, female patients are positively associated with HBL. CONCLUSION: In
      our study, we found HBL is a significant segment of TBL and is much larger than
      what we considered previously in LAG for gastric cancer. Gender, hypertension,
      and albumin loss are significantly correlated with HBL. Therefore, paying
      attention to HBL is significant for promoting clinical treatment and ensuring
      patients' safety.

PMID- 29064311
TI  - Transanal Endoscopic Microsurgery Implementation in Ultra-Low Anterior Resection.
AB  - BACKGROUND: Distal rectal cancer resection is an ongoing challenge for the
      colorectal surgeon. In recent years new technical approaches, especially with
      implementation of transanal platforms were developed to help in the visualization
      and resection of these tumors. Nevertheless, the use of these platforms is
      demanding with significant complications during the onset phase. METHODS:
      Patients with very low rectal cancer were operated on in a single tertiary center
      with a combined abdominal and transanal endoscopic microsurgery (TEM) approach.
      Demographic, pathological, and surgical data were collected retrospectively with
      an emphasis on distal margin involvement. RESULTS: Nineteen patients were
      operated on during the study period. All patients had negative distal resection
      margins with a low complication rate. The distant metastasis and local recurrence
      rates were low with a mean follow-up of 2 years. CONCLUSIONS: TEM provides an
      appealing and viable option for the resection of low rectal cancer in a combined
      transabdominal and transanal approach in patients with a good response after
      neoadjuvant treatment. This is one of the available platforms a colorectal
      surgeon might benefit from having in his armamentarium. It has a very low
      complication rate with maintenance of oncological principles, enabling a clear
      visualization of the distal rectum, and thus ensures free distal resection
      margins.

PMID- 29064312
TI  - Percutaneous pinning versus volar locking plate internal fixation for unstable
      distal radius fractures: a meta-analysis.
AB  - : This meta-analysis compared outcomes between percutaneous pinning/wiring and
      open reduction internal fixation (ORIF) with locking plates for treatment of
      unstable distal radius fractures. Medline, Cochrane, EMBASE, and Google Scholar
      were searched through December 30, 2015. Twenty randomised controlled trials
      (RCTs) and non-randomised two-arm studies were included. Outcomes included scores
      of Disabilities of the Arms, Shoulders and Hands (DASH), visual analogue scale
      (VAS) pain, and patient rated wrist evaluation (PRWE) score, as well as range of
      motion (ROM) and complication incidence. ORIF/plating was associated with lower
      DASH scores but longer procedure time, while there was no difference between the
      two methods with respect to VAS pain score and PRWE score. The overall incidence
      of complications, including complex regional pain syndrome, was higher with
      pinning/wiring, though the incidence of carpal tunnel syndrome and nerve defects
      was not different. Supination and grip strength were better with ORIF.
      Radiographically, ulnar variation was greater with pinning/wiring. These results
      suggest that ORIF/plating is the preferred method of managing unstable distal
      radius fractures. LEVEL OF EVIDENCE: II.

PMID- 29064313
TI  - National Multispecialty Survey Results: Comparing Morbidity and Mortality
      Conference Practices within and outside Otolaryngology.
AB  - Objective The objective is to describe variations in the otolaryngology morbidity
      and mortality (M&M) conference and to compare with other specialties. Design
      Cross-sectional survey. Setting The setting included otolaryngology departments
      across the United States and nonotolaryngology medical and surgical departments
      at 4 academic medical centers. Subjects and Methods Participants were members of
      a national otolaryngology quality/safety network and nonotolaryngology quality
      leaders at 4 large academic hospitals. Surveys were administered January 2017.
      Respondents described M&M conference practices, goals, and educational role.
      Results Twenty-eight of 39 individuals representing 28 institutions completed the
      otolaryngology survey (72% response rate). Of 197 individuals, 60 (30% response
      rate) representing 11 surgical and 20 nonsurgical specialties completed the
      comparison survey. Twenty-seven of 28 otolaryngologists (46 of 60
      nonotolaryngologists) worked in academic settings. All otolaryngology programs
      conducted an M&M conference: 54% discussed all adverse events and errors; 32%
      used standard case selection processes; 70% used structured discussion, usually
      root cause analysis (64%); and 32% classified harm level. In comparison with
      other specialties, otolaryngology programs were more likely to discuss all
      adverse events and errors ( P = .01). Most conferences led to quality projects
      and intrainstitutional communication: 22% communicated to patients and families;
      73% of respondents thought that M&M conferences should be standardized or use
      "best practices." In both surveys, improving patient care was rated the
      conference's most important function, followed by trainee education and culture
      change. Patient care and practice-based learning were rated the most relevant
      Accreditation Council for Graduate Medical Education Core Competencies in both
      surveys. Conclusions Academic otolaryngology M&M practices generally align with
      other specialties, but specifics vary widely, making collaborative quality
      improvement challenging. Educational and administrative priorities cross
      specialties. Most respondents thought that standardization and best practices are
      worthwhile. Nonacademic practice data are needed.

PMID- 29064314
TI  - Rituximab in pemphigus.
AB  - Pemphigus is a severe autoimmune blistering disease mediated by pathogenic anti
      desmoglein antibodies leading to an inter keratinocyte disjunction. Rituximab is
      a monoclonal antibody that binds to the CD-20 antigen of B lymphocytes, which
      causes B-cell depletion and a subsequent reduction in pathogenic autoantibodies.
      Its therapeutic role in pemphigus has been progressively growing with increasing
      evidence of successful outcomes. Rituximab was initially off-labeled used as an
      alternative in patients with recalcitrant or relapsing pemphigus and in patients
      with contraindications to systemic corticosteroids. Recently, a large randomized
      clinical trial has shown that first-line use of rituximab combined with short
      term prednisone regimen was both more effective and potentially safer than a
      standard regimen of high doses of corticosteroids in patients with moderate to
      severe pemphigus.

PMID- 29064316
TI  - Quality of Life in Women with Endometriosis: An Integrative Review.
AB  - OBJECTIVE: The purpose of this study was to conduct an integrative review of the
      health-related quality of life (QoL) burden in women with endometriosis.
      MATERIALS AND METHODS: This integrative review was carried out by consulting the
      BIREME/MEDLINE databases through July 2017. We searched for articles published in
      the past 12 years using the MeSH terms "quality of life" and "endometriosis" and
      its representations in Portuguese and English. RESULTS: Database search yielded
      367 records, and eight additional records were identified through other sources.
      After analyzing articles based on inclusion and exclusion criteria, rigor and
      methodological evidence, 26 publications constituted the final corpus of our
      analysis. Generic instruments most commonly used to assess QoL included the Short
      Form Health Survey (SF-36), World Health Organization Quality of Life Assessment
      bref (WHOQOL-bref); the 12-item Short Form Health Survey (SF-12), and the Duke
      Health Profile, among others. Disease-specific questionnaires were also used, and
      two studies collected qualitative data. Endometriosis had a negative impact in
      all domains of QoL, which was more associated to symptoms than to the diagnosis
      per se. It also negatively affected sleep quality and perceived stress. Impact
      had age-related differences in most studies, and was not related to endometriosis
      staging. CONCLUSIONS: Endometriosis negatively affects QoL. A consensus must be
      reached as to which QoL instrument should be used to make studies comparable.

PMID- 29064315
TI  - Safety and efficacy of helminth treatment in relapsing-remitting multiple
      sclerosis: Results of the HINT 2 clinical trial.
AB  - BACKGROUND: The hygiene hypothesis suggests that microbial replacement may be
      therapeutic in allergic and autoimmune diseases. Nevertheless, the results of
      helminth treatment, including in multiple sclerosis (MS), have been inconclusive.
      OBJECTIVE: To assess safety and brain magnetic resonance imaging (MRI) activity
      in subjects with relapsing-remitting multiple sclerosis (RRMS) during oral
      administration of ova from the porcine whipworm, Trichuris suis (TSO). METHODS: A
      total of 16 disease-modifying treatment (DMT) naive RRMS subjects were studied in
      a baseline versus treatment (BVT) controlled prospective study. MRI scans were
      performed during 5 months of screening-observation, 10 months of treatment, and 4
      months of post-treatment surveillance. RESULTS: No serious symptoms or adverse
      events occurred during treatment. For the cohort, there was a trend consistent
      with a 35% diminution in active lesions when observation MRIs were compared to
      treatment MRIs ( p = 0.08), and at the level of individuals, 12 of 16 subjects
      improved during TSO treatment. T regulatory lymphocytes were increased during TSO
      treatment. CONCLUSION: TSO is safe in RRMS subjects. Potentially favorable MRI
      outcomes and immunoregulatory changes were observed during TSO treatment;
      however, the magnitude of these effects was modest, and there was considerable
      variation among the responses of individual subjects.

PMID- 29064317
TI  - Executive Functions, Trait Self-Control, and the Intention-Behavior Gap in
      Physical Activity Behavior.
AB  - Many people fail to translate their physical activity intentions into behavior.
      This intention-behavior gap can be explained by (a) explicit trait self-control,
      (b) implicit executive functions, and (c) their interactions. In 118
      participants, the intention-behavior gap was measured in a prospective design.
      Trait self-control was assessed via self-report questionnaires, whereas executive
      functioning was measured with test performance in inhibition, updating, and
      shifting at baseline. Regression analysis showed that (a) higher trait self
      control predicts a smaller intention-behavior gap; (b) updating performance is
      related with this gap; and (c) behavior in tests on inhibition, updating, and
      shifting moderate the relation between the trait self-control and the intention
      behavior gap. The present study showed that the complex pattern that modulates
      the relation between intended and realized physical activity behavior includes
      trait self-control, executive functions, as well as the combination of these
      cognitive components supporting dual-process approaches of self-control including
      implicit and explicit processing components.

PMID- 29064318
TI  - Comparing the performance of people who stutter and people who do not stutter on
      the Test of Everyday Attention.
AB  - INTRODUCTION: Compelling findings into the relationship between stuttering and
      attentional ability have started to emerge, with some child and adult studies
      indicating poorer attentional ability among people who stutter (PWS). The purpose
      of the present research was to provide a more complete picture of the attentional
      abilities of PWS, as well as to gather insights into their individual attentional
      performance. METHOD: We compared the attentional ability of PWS to that of people
      who do not stutter (PWNS) by using the Test of Everyday Attention (TEA). TEA is a
      clinical assessment battery with a very good validity and reliability comprising
      8 subtests that pose differential demands on sustained attention, selective
      attention, attentional switching, and divided attention. Fifty age- and gender
      matched PWS and PWNS (aged 19-77 years) took part in the study. Importantly, we
      also examined stuttering severity in the PWS group. RESULTS: PWS performed
      significantly worse on tasks tapping into visual selective and divided
      attentional resources. Furthermore despite failing to reach statistical
      significance, the results also revealed an interesting trend for stuttering to be
      associated with poorer performance on two subtests measuring attentional
      switching and one tapping into auditory selective attention. Moreover, as
      hypothesized, there was also a negative association between stuttering severity
      and performance on two TEA subtests measuring visual selective attention.
      Finally, the type of TEA test variant produced no significant effect on
      performance. CONCLUSIONS: We interpret these results as indicative of stuttering
      being associated with poorer performance on tasks measuring certain attentional
      abilities. These tie in well with theoretical models identifying speech
      production as particularly attention-demanding in stuttering or approaches
      placing attentional dysfunction at the heart of the condition. The present
      research also has practical implications for the use of attentional training to
      improve fluency.

PMID- 29064319
TI  - Short- versus Long-term Stenting in Children with Subglottic Stenosis Undergoing
      Laryngotracheal Reconstruction.
AB  - Objectives Suprastomal stents are routinely used in laryngotracheal
      reconstruction (LTR) to stabilize grafts and provide framework to sites of
      repair. However, the duration of stenting varies according to patient history and
      physician preference. We examined outcomes of short- versus long-term stenting in
      children with subglottic stenosis (SGS) undergoing LTR. Study Design Case series
      with chart review. Setting Tertiary care pediatric hospital. Subjects and Methods
      Thirty-six children <18 years old who underwent double-stage LTR for SGS from
      January 2012 to January 2015 were included. Demographic data, stenosis grade, and
      decannulation rates were compared between children with short-term stenting (<=21
      days; n = 14) and those with long-term stenting (>21 days; n = 22). Results No
      significant difference between groups was seen for sex, age, race, or previous
      repair. Children in the short-term group were stented for 10.9 +/- 4.9 days,
      compared with 44.0 +/- 10.6 for those long-term ( P < .0001). A similar number of
      children with short- versus long-term stents had grade 3/4 stenosis
      preoperatively (71.4% vs 77.2%). Although time to decannulation was not
      significantly different, 72.7% of children with long-term stents were
      decannulated, as opposed to 35.7% with short-term stents ( P = .03). After
      adjusting for grade at surgery and age, children with long-term stents had 4.3
      greater odds (95% CI, 1.0-18.3) of decannulation than children with short-term
      stents. Conclusions Children with long-term stenting were more likely to be
      successfully decannulated. Although long-term stenting improved outcomes for
      children with SGS, additional research is needed to better define ideal
      candidates for short- versus long-term stenting.

PMID- 29064320
TI  - The Hospital-Acquired Conditions (HAC) reduction program: using cranberry
      treatment to reduce catheter-associated urinary tract infections and avoid
      Medicare payment reduction penalties.
AB  - OBJECTIVE: The Affordable Care Act (ACA) established the Hospital-Acquired
      Condition (HAC) Reduction Program. The Centers for Medicare and Medicaid Services
      (CMS) established a total HAC scoring methodology to rank hospitals based upon
      their HAC performance. Hospitals that rank in the lowest quartile based on their
      HAC score are subject to a 1% reduction in their total Medicare reimbursements.
      In FY 2017, 769 hospitals incurred payment reductions totaling $430 million. This
      study analyzes how improvements in the rate of catheter-associated urinary tract
      infections (CAUTI), based on the implementation of a cranberry-treatment regimen,
      impact hospitals' HAC scores and likelihood of avoiding the Medicare
      reimbursement penalty. METHODS: A simulation model is developed and implemented
      using public data from the CMS' Hospital Compare website to determine how
      hospitals' unilateral and simultaneous adoption of cranberry to improve CAUTI
      outcomes can affect HAC scores and the likelihood of a hospital incurring the
      Medicare payment reduction, given results on cranberry effectiveness in
      preventing CAUTI based on scientific trials. The simulation framework can be
      adapted to consider other initiatives to improve hospitals' HAC scores. RESULTS:
      Nearly all simulated hospitals improved their overall HAC score by adopting
      cranberry as a CAUTI preventative, assuming mean effectiveness from scientific
      trials. Many hospitals with HAC scores in the lowest quartile of the HAC-score
      distribution and subject to Medicare reimbursement reductions can improve their
      scores sufficiently through adopting a cranberry-treatment regimen to avoid
      payment reduction. LIMITATIONS: The study was unable to replicate exactly the
      data used by CMS to establish HAC scores for FY 2018. The study assumes that
      hospitals subject to the Medicare payment reduction were not using cranberry as a
      prophylactic treatment for their catheterized patients, but is unable to confirm
      that this is true in all cases. The study also assumes that hospitalized catheter
      patients would be able to consume cranberry in either juice or capsule form, but
      this may not be true in 100% of cases. CONCLUSION: Most hospitals can improve
      their HAC scores and many can avoid Medicare reimbursement reductions if they are
      able to attain a percentage reduction in CAUTI comparable to that documented for
      cranberry-treatment regimes in the existing literature.

PMID- 29064321
TI  - Metabolic syndrome in menopause and associated factors: a meta-analysis.
AB  - OBJECTIVE: Metabolic syndrome (MetS) is a cluster of risk factors for
      cardiovascular disease and diabetes. Menopause is associated with an increased
      risk for MetS. The purpose of this meta-analysis is to better understand the
      relationship between MetS and menopause. METHODS: MEDLINE and EMBASE were
      searched for all the associated articles on (1) MetS components in postmenopausal
      women vs. premenopausal women, (2) comparison of MetS incidence between surgical
      menopause and natural menopause, (3) the effect of hormone therapy (HT) with
      17beta-estradiol (E2) compared to conjugated equine estrogen (CEE) on MetS
      components among postmenopausal women. A meta-analysis was applied by Review
      Manager 5.3 software. RESULTS: All comparable indicators were significantly
      unfavorably changed in postmenopausal women compared to premenopausal women
      except for high density lipoprotein cholesterol. Women who underwent surgical
      menopause suffered a 1.51-fold higher risk for MetS compared to those with
      natural menopause. HT with E2 provided more benefits for levels of triglyceride
      and diastolic blood, while CEE showed a better effect on both high and low
      density lipoprotein cholesterol levels. CONCLUSIONS: Menopause nearly adversely
      affects all components of MetS, and surgical menopause may lead to a higher
      incidence of MetS compared to natural menopause. HT with various preparations may
      have different effects on MetS components. These results may clarify the
      management of menopause-related MetS in clinical practice.

PMID- 29064322
TI  - Interaction mechanism of insulin with ZnO nanoparticles by replica exchange
      molecular dynamics simulation.
AB  - The interaction of ZnO nanoparticles with biological molecules such as proteins
      is one of the most important and challenging problems in molecular biology.
      Molecular dynamics (MD) simulations are useful technique for understating the
      mechanism of various interactions of proteins and nanoparticles. In the present
      work, the interaction mechanism of insulin with ZnO nanoparticles was studied.
      Simulation methods including MD and replica exchange molecular dynamics (REMD)
      and their conditions were surveyed. According to the results obtained by REMD
      simulation, it was found that insulin interacts with ZnO nanoparticle surface via
      its polar and charged amino acids. Unfolding insulin at ZnO nanoparticle surface,
      the terminal parts of its chains play the main role. Due to the linkage between
      chain of insulin and chain of disulfide bonds, opposite directional movements of
      N terminal part of chain A (toward nanoparticle surface) and N termini of chain B
      (toward solution) make insulin unfolding. In unfolding of insulin at this
      condition, its helix structures convert to random coils at terminal parts chains.

PMID- 29064324
TI  - 2D-QSAR study, molecular docking, and molecular dynamics simulation studies of
      interaction mechanism between inhibitors and transforming growth factor-beta
      receptor I (ALK5).
AB  - Transforming growth factor type 1 receptor (ALK5) is kinase associated with a
      wide variety of pathological processes, and inhibition of ALK5 is a good strategy
      to treat many kinds of cancer and fibrotic diseases. Recently, a series of
      compounds have been synthesized as ALK5 inhibitors. However, the study of their
      selectivity against other potential targets remains elusive. In this research, a
      data-set of ALK5 inhibitors were collected and studied based on the combination
      of 2D-QSAR, molecular docking and molecular dynamics simulation. The quality of
      QSAR models were assessed statistically by F, R2, and R2ADJ, proved to be
      credible. The cross-validations for the models (q2LOO = 0.571 and 0.629,
      respectively) showed their robustness, while the external validations (r2test =
      0.703 and 0.764, respectively) showed their predictive power. Besides, the
      predicted binding free energy results calculated by MM/GBSA method were in
      accordance with the experimental data, and the van der Waals energy term was the
      factor that had the most significant impact on ligand binding. What is more,
      several important residues were found to significantly affect the binding
      affinity. Finally, based on our analyses above, a proposed series of molecules
      were designed.

PMID- 29064325
TI  - Real-world treatment patterns and outcomes of omalizumab use in patients with
      chronic idiopathic urticaria.
AB  - OBJECTIVE: To examine treatment patterns, treatment response, and demographic and
      clinical characteristics of patients with chronic idiopathic urticaria (CIU)
      newly initiated on omalizumab therapy in real-world practice in the US. METHODS:
      This retrospective observational cohort study used US claims data from the
      HealthCore Integrated Research Database (HIRD(r)) augmented with medical record
      data to identify CIU patients newly-treated with omalizumab (>=4 omalizumab
      claims within 6 months of initial claim; index date = first omalizumab claim
      date) between March 21, 2014 and October 31, 2015 and with >=6 months pre- and
      >=12 months post-index health plan eligibility. Study outcomes were captured from
      medical records for up to 12 months pre-index and up to 24 months post-index.
      Descriptive statistics were reported. RESULTS: This study consisted of 88
      patients with a mean (SD) age of 43.4 (+/- 13.46) years, 68.2% were female, and
      36 patients had >=18 months post-index eligibility. Among 69 patients with
      documented index dose, 75.4% received omalizumab 300 mg and 69.6% remained on
      index dose throughout follow-up. For 52 patients with documented index dosing
      frequency, 96.2% had every 4-week dosing frequency. Among 86 patients with
      omalizumab documentation, 83.7% reported CIU improvement after omalizumab
      initiation and 24.4% discontinued omalizumab. For all patients, the proportion
      using oral corticosteroids (OCS) decreased pre- to post-index (52.3% vs 39.8%).
      Similar results were observed for patients with >=18 months post-index
      eligibility. CONCLUSIONS: In this real-world analysis, the majority of patients
      remained on omalizumab for >=12 months, and had a positive response. OCS use
      decreased following omalizumab initiation.

PMID- 29064323
TI  - Non-invasive imaging of global and regional cardiac function in pulmonary
      hypertension.
AB  - Pulmonary hypertension (PH) is a progressive illness characterized by elevated
      pulmonary artery pressure; however, the main cause of mortality in PH patients is
      right ventricular (RV) failure. Historically, improving the hemodynamics of
      pulmonary circulation was the focus of treatment; however, it is now evident that
      cardiac response to a given level of pulmonary hemodynamic overload is variable
      but plays an important role in the subsequent prognosis. Non-invasive tests of RV
      function to determine prognosis and response to treatment in patients with PH is
      essential. Although the right ventricle is the focus of attention, it is clear
      that cardiac interaction can cause left ventricular dysfunction, thus
      biventricular assessment is paramount. There is also focus on the atrial chambers
      in their contribution to cardiac function in PH. Furthermore, there is evidence
      of regional dysfunction of the two ventricles in PH, so it would be useful to
      understand both global and regional components of dysfunction. In order to
      understand global and regional cardiac function in PH, the most obvious non
      invasive imaging techniques are echocardiography and cardiac magnetic resonance
      imaging (CMRI). Both techniques have their advantages and disadvantages.
      Echocardiography is widely available, relatively inexpensive, provides
      information regarding RV function, and can be used to estimate RV pressures.
      CMRI, although expensive and less accessible, is the gold standard of
      biventricular functional measurements. The advent of 3D echocardiography and
      techniques including strain analysis and stress echocardiography have improved
      the usefulness of echocardiography while new CMRI technology allows the
      measurement of strain and measuring cardiac function during stress including
      exercise. In this review, we have analyzed the advantages and disadvantages of
      the two techniques and discuss pre-existing and novel forms of analysis where
      echocardiography and CMRI can be used to examine atrial, ventricular, and
      interventricular function in patients with PH at rest and under stress.

PMID- 29064326
TI  - Ligand- and structure-based in silico studies to identify kinesin spindle protein
      (KSP) inhibitors as potential anticancer agents.
AB  - Kinesin spindle protein (KSP) belongs to the kinesin superfamily of microtubule
      based motor proteins. KSP is responsible for the establishment of the bipolar
      mitotic spindle which mediates cell division. Inhibition of KSP expedites the
      blockade of the normal cell cycle during mitosis through the generation of
      monoastral MT arrays that finally cause apoptotic cell death. As KSP is highly
      expressed in proliferating/cancer cells, it has gained considerable attention as
      a potential drug target for cancer chemotherapy. Therefore, this study envisaged
      to design novel KSP inhibitors by employing computational techniques/tools such
      as pharmacophore modelling, virtual database screening, molecular docking and
      molecular dynamics. Initially, the pharmacophore models were generated from the
      data-set of highly potent KSP inhibitors and the pharmacophore models were
      validated against in house test set ligands. The validated pharmacophore model
      was then taken for database screening (Maybridge and ChemBridge) to yield hits,
      which were further filtered for their drug-likeliness. The potential hits
      retrieved from virtual database screening were docked using CDOCKER to identify
      the ligand binding landscape. The top-ranked hits obtained from molecular docking
      were progressed to molecular dynamics (AMBER) simulations to deduce the ligand
      binding affinity. This study identified MB-41570 and CB-10358 as potential hits
      and evaluated these experimentally using in vitro KSP ATPase inhibition assays.

PMID- 29064328
TI  - The story of 'Scientist: The Story of a Word'.
AB  - This examination of an important paper by Sydney Ross is the first in a projected
      series of occasional reflections on 'Annals of Science Classic Papers' that have
      had enduring utility within the field of history of science and beyond. First the
      messages of the paper are examined, some well known but others, particularly
      Ross's own contemporary concerns about the use of the word 'scientist', less so.
      The varied uses made of the paper by scholars are then traced before Ross's
      biography is examined in order to try to understand how a figure professionally
      marginal to the field of history of science came to write such a significant
      piece. Ross's interest in the topic appears to have been informed by a
      romantically tinged scientific progressivism and a deep concern with the
      importance of linguistic precision in science and in public affairs. The
      inspirations of the author and the interests of his audience have been only
      partially aligned, but the paper's insights remain of broad historical interest
      and have wider ramifications since the denotation 'scientist' and its proper
      application are much debated today in contests over the authority of science.

PMID- 29064327
TI  - The expression of APE1 in triple-negative breast cancer and its effect on drug
      sensitivity of olaparib.
AB  - Triple-negative breast cancer is a kind of breast cancer with poor prognosis and
      special biological behavior, which lacked endocrine therapy and targeted therapy.
      We investigate the effect of human APE1 (apurinic/apyrimidyl endonuclease 1), a
      rate-limiting enzyme of base excision repair, on the prognosis in triple-negative
      breast cancer and drug sensitivity of olaparib. The expression of APE1 was
      detected by immunohistochemistry in the triple-negative breast cancer tissues and
      its effect on survival of triple-negative breast cancer patients was followed. To
      find whether APE1 effect the drug sensitivity in triple-negative breast cancer
      cells, the APE1-knockout HCC1937 cell line (triple-negative breast cancer cell
      line) was established by CRISPR/Cas9 system. Then, we use the wild-type and
      knockout one to test the drug sensitivity of olaparib. The expression of APE1 in
      triple-negative breast cancer tissues was significantly higher than that in the
      adjacent tissues (85.6% vs 14.4%) and its expression was related to tumor size (p
      < 0.05). We also found that it is an independent prognostic factor in patients
      with triple-negative breast cancer (overall survival, p = 0.01). In vitro assay,
      the half maximal inhibitory concentration of olaparib in HCC1937-APE1-KO was
      significantly increased (17.22 vs 91.85 MUM) compared to the wild type. The
      growth curve showed that olaparib had a stronger lethality on HCC1937 compared to
      HCC1937- APE1-KO (p < 0.05 on day 3). HCC1937 resulted in more mitotic G2/M
      arrest and increased apoptosis rate after treatment with 40 MUM of olaparib,
      while HCC1937-APE1-KO did not change significantly. When HCC1937 was treated with
      different concentrations of olaparib, it was found that APE1 expression decreased
      more significantly at 15 MUM of olaparib was. In HCC1937-APE1-KO, the expression
      of endogenous poly (ADP-ribose) polymerase 1 was also less than that of HCC1937.
      These results suggested that the expression of APE1 was an important basis for
      the maintenance of poly (ADP-ribose) polymerase 1, and the deletion of APE1 may
      be related to the resistance of olaparib.

PMID- 29064329
TI  - Erratum.
AB  - Alghadir, A., Zafar, H., Iqbal, Z. A., Al-Eisa, E. (2017). Work-related low back
      pain among physical therapists in Riyadh, Saudi Arabia. Workplace Health &
      Safety, 65(8), 337-345. (Original DOI: 10.1177/2165079916670167). The following
      acknowledgment should have been included in this article. The text is included
      below. Acknowledgment The authors are grateful to the Deanship of Scientific
      Research, King Saud University for funding through Vice Deanship of Scientific
      Research Chairs.

PMID- 29064330
TI  - Augmented Intelligence: Enhancing the Roles of Health Actuaries and Health
      Economists for Population Health Management.

PMID- 29064331
TI  - Patent Highlights June-July 2017.
AB  - A snapshot of noteworthy recent developments in the patent literature of
      relevance to pharmaceutical and medical research and development.

PMID- 29064332
TI  - Use of prothrombin complex concentrate containing heparin for emergency reversal
      of bivalirudin anticoagulation: a word of caution.

PMID- 29064333
TI  - Molecular Detection and Serological Evidence of Tick-Borne Encephalitis Virus in
      Serbia.
AB  - Tick-borne encephalitis (TBE) is a zoonotic flaviviral infection that is a
      growing public health concern in European countries. The aims of this research
      were to detect and characterize tick-borne encephalitis virus (TBEV) in Ixodes
      ricinus ticks at presumed natural foci in Serbia, and to determine seroprevalence
      of TBEV IgG antibodies in humans and animals. A total of 500 I. ricinus ticks
      were examined for the presence of TBEV by real-time RT-PCR, and conventional
      nested PCR and sequencing. To determine TBEV seroprevalence, 267 human sera
      samples were collected, as were 200 sera samples from different animal species.
      All sera samples were examined by ELISA for the presence of anti-TBEV antibodies.
      To exclude cross-reactivity, all sera samples were tested for anti-West Nile
      virus (WNV) antibodies and all human sera samples were also tested for anti-Usutu
      virus antibodies by ELISA. Results of this preliminary study indicated TBEV
      activity in Serbia at two microfoci. Several decades after the previous
      documentation of TBEV in Serbia, we have demonstrated the presence of TBEV in I.
      ricinus questing nymphs (prevalence 2% and 6.6% at the two different localities)
      and anti-TBEV antibodies in humans (seroprevalence 0.37%). Moreover, we show for
      the first time TBEV seroprevalence in several animal species in Serbia, including
      dogs (seroprevalence 17.5%), horses (5%), wild boars (12.5%), cattle (2.5%), and
      roe deer (2.5%). None of the goats tested was positive for anti-TBEV IgG
      antibodies. TBEV isolate from I. ricinus tick in this study belonged to the
      Western European subtype. To understand the true public health concern in Serbia,
      detailed epidemiological, clinical, virological, and acarological research are
      required. This is important for implementation of effective control measures to
      reduce the incidence of TBE in Serbia.

PMID- 29064334
TI  - Melanoma treatment with intratumoral electroporation of tavokinogene telseplasmid
      (pIL-12, tavokinogene telseplasmid).
AB  - Tumors evade detection and/or clearance by the immune system via multiple
      mechanisms. IL-12 is a potent immunomodulatory cytokine that plays a central role
      in immune priming. However, systemic delivery of IL-12 can result in life
      threatening toxicity and therefore has shown limited efficacy at doses that can
      be safely administered. We developed an electroporation technique to produce
      highly localized IL-12 expression within tumors leading to regression of both
      treated and untreated lesions in animal models and in patients with a favorable
      safety profile. Furthermore, intratumoral tavokinogene telseplasmid
      electroporation can drive cellular immune responses, converting 'cold' tumors
      into 'hot' tumors. Clinical trials are ongoing to determine whether intratumoral
      tavokinogene telseplasmid electroporation synergizes with checkpoint blockade
      therapy in immunologically cold tumors predicted not to respond to PD-1 antibody
      monotherapy.

PMID- 29064335
TI  - Overall Safety of Ospemifene in Postmenopausal Women from Placebo-Controlled
      Phase 2 and 3 Trials.
AB  - OBJECTIVE: To evaluate the safety of daily oral ospemifene 60 mg, estrogen
      agonist/antagonist, used to treat moderate-to-severe dyspareunia due to
      postmenopausal vulvovaginal atrophy, which is part of genitourinary syndrome of
      menopause. METHODS: Post hoc analysis of safety data (treatment-emergent adverse
      events [TEAEs]) pooled from six phase 2 and 3 randomized, double-blind,
      multicenter placebo-controlled studies, evaluating the effects of ospemifene 60
      mg on the breast, cardiovascular system, and bone in postmenopausal women.
      RESULTS: At least one TEAE was reported by 67.6% (840/1242) and 54.1% (518/958)
      of women taking ospemifene 60 mg and placebo, respectively. Most TEAEs were mild
      or moderate and occurred within 4 to 12 weeks. The most commonly reported TEAEs
      with ospemifene were hot flush (8.5% vs. 3.3% for placebo) and urinary tract
      infection (6.5% vs. 4.8%). Discontinuation due to TEAEs was 7.6% with ospemifene
      and 3.8% with placebo. Most women discontinued treatment due to adverse events
      (AEs): hot flushes, muscle spasms, headache, and vaginal discharge. Serious AEs
      occurred infrequently (ospemifene, 2.6%; placebo, 1.8%); most were not considered
      related to treatment. Breast cancer and other breast-related TEAE incidences were
      comparable between ospemifene (2.5%) and placebo (2.2%), and cardiovascular TEAE
      incidence, including deep vein thrombosis, was low with ospemifene (0.3%) and
      placebo (0.1%). CONCLUSION: No unexpected safety signals were reported, and
      discontinuation due to TEAEs was low, with use of ospemifene 60 mg versus placebo
      in six phase 2 and 3 trials, suggesting a lack of detrimental effects on the
      breast, bone, and cardiovascular health of postmenopausal women when ospemifene
      is used to effectively treat moderate-to-severe postmenopausal dyspareunia.

PMID- 29064336
TI  - The effect of dim light at night on cerebral hemodynamic oscillations during
      sleep: A near-infrared spectroscopy study.
AB  - Recent studies have reported that dim light at night (dLAN) is associated with
      risks of cardiovascular complications, such as hypertension and carotid
      atherosclerosis; however, little is known about the underlying mechanism. Here,
      we evaluated the effect of dLAN on the cerebrovascular system by analyzing
      cerebral hemodynamic oscillations using near-infrared spectroscopy (NIRS).
      Fourteen healthy male subjects underwent polysomnography coupled with cerebral
      NIRS. The data collected during sleep with dim light (10 lux) were compared with
      those collected during sleep under the control dark conditions for the sleep
      structure, cerebral hemodynamic oscillations, heart rate variability (HRV), and
      their electroencephalographic (EEG) power spectrum. Power spectral analysis was
      applied to oxy-hemoglobin concentrations calculated from the NIRS signal.
      Spectral densities over endothelial very-low-frequency oscillations (VLFOs)
      (0.003-0.02 Hz), neurogenic VLFOs (0.02-0.04 Hz), myogenic low-frequency
      oscillations (LFOs) (0.04-0.15 Hz), and total LFOs (0.003-0.15 Hz) were obtained
      for each sleep stage. The polysomnographic data revealed an increase in the N2
      stage under the dLAN conditions. The spectral analysis of cerebral hemodynamics
      showed that the total LFOs increased significantly during slow-wave sleep (SWS)
      and decreased during rapid eye movement (REM) sleep. Specifically, endothelial
      (median of normalized value, 0.46 vs. 0.72, p = 0.019) and neurogenic (median,
      0.58 vs. 0.84, p = 0.019) VLFOs were enhanced during SWS, whereas endothelial
      VLFOs (median, 1.93 vs. 1.47, p = 0.030) were attenuated during REM sleep. HRV
      analysis exhibited altered spectral densities during SWS induced by dLAN,
      including an increase in very-low-frequency and decreases in low-frequency and
      high-frequency ranges. In the EEG power spectral analysis, no significant
      difference was detected between the control and dLAN conditions. In conclusion,
      dLAN can disturb cerebral hemodynamics via the endothelial and autonomic systems
      without cortical involvement, predominantly during SWS, which might represent an
      underlying mechanism of the increased cerebrovascular risk associated with light
      exposure during sleep.

PMID- 29064338
TI  - Corrigendum.

PMID- 29064337
TI  - David Bowie and the Art of Slow Innovation: A Fast-Second Winner Strategy for
      Biotechnology and Precision Medicine Global Development.
AB  - Original ideas and innovation cannot always be ordered like a courier service and
      delivered fresh to our desk at 9 am. Yet, most creativity-based organizations,
      careers, and professions, science and biotechnology innovation included,
      emphasize the speed as the prevailing ideology. But a narrow focus on speed has
      several and overlooked shortcomings. For example, it does not offer the
      opportunity to draw from, and stitch together disparate concepts and practices
      for truly disruptive innovation. Preventing false starts, learning from others'
      or our own mistakes, and customizing innovations for local community needs are
      difficult in a speed-hungry innovation ecosystem. We introduce a new strategy,
      the Fast-Second Winner, specifically in relation to global development of
      biotechnologies and precision medicine. This a la carte global development
      strategy envisions a midstream entry into the innovation ecosystem. Moreover, we
      draw from the works of the late David Bowie who defied rigid classifications as
      an artist and prolific innovator, and introduce the concept and practice of slow
      innovation that bodes well with the Fast-Second Winner strategy. A type of slow
      innovation, the Fast-Second Winner is actually fast and sustainable in the long
      term, and efficient by reducing false starts in new precision medicine
      application contexts and geographies, learning from other innovators' failures,
      and shaping innovations for the local community needs. The establishment of
      Centers for Fast-Second Innovation (CFSIs), and their funding, for example, by
      crowdfunding and other innovative mechanisms, could be timely for omics and
      precision medicine global development. If precision medicine is about tailoring
      drug treatments and various health interventions to individuals, we suggest to
      start from tailoring new ideas, and focus not only on how much we innovate but
      also what and how we innovate. In principle, the Fast-Second Winner can be
      applied to omics and other biotechnology responsible development in medical
      practice or any field of applied innovation.

PMID- 29064339
TI  - The Neurobiology of Agrammatic Sentence Comprehension: A Lesion Study.
AB  - Broca's area has long been implicated in sentence comprehension. Damage to this
      region is thought to be the central source of "agrammatic comprehension" in which
      performance is substantially worse (and near chance) on sentences with
      noncanonical word orders compared with canonical word order sentences (in
      English). This claim is supported by functional neuroimaging studies
      demonstrating greater activation in Broca's area for noncanonical versus
      canonical sentences. However, functional neuroimaging studies also have
      frequently implicated the anterior temporal lobe (ATL) in sentence processing
      more broadly, and recent lesion-symptom mapping studies have implicated the ATL
      and mid temporal regions in agrammatic comprehension. This study investigates
      these seemingly conflicting findings in 66 left-hemisphere patients with chronic
      focal cerebral damage. Patients completed two sentence comprehension measures,
      sentence-picture matching and plausibility judgments. Patients with damage
      including Broca's area (but excluding the temporal lobe; n = 11) on average did
      not exhibit the expected agrammatic comprehension pattern-for example, their
      performance was >80% on noncanonical sentences in the sentence-picture matching
      task. Patients with ATL damage ( n = 18) also did not exhibit an agrammatic
      comprehension pattern. Across our entire patient sample, the lesions of patients
      with agrammatic comprehension patterns in either task had maximal overlap in
      posterior superior temporal and inferior parietal regions. Using voxel-based
      lesion-symptom mapping, we find that lower performances on canonical and
      noncanonical sentences in each task are both associated with damage to a large
      left superior temporal-inferior parietal network including portions of the ATL,
      but not Broca's area. Notably, however, response bias in plausibility judgments
      was significantly associated with damage to inferior frontal cortex, including
      gray and white matter in Broca's area, suggesting that the contribution of
      Broca's area to sentence comprehension may be related to task-related cognitive
      demands.

PMID- 29064340
TI  - Transcranial Cerebellar Direct Current Stimulation Enhances Verb Generation but
      Not Verb Naming in Poststroke Aphasia.
AB  - Although the role of the cerebellum in motor function is well recognized, its
      involvement in the lexical domain remains to be further elucidated. Indeed, it
      has not yet been clarified whether the cerebellum is a language structure per se
      or whether it contributes to language processing when other cognitive components
      (e.g., cognitive effort, working memory) are required by the language task.
      Neuromodulation studies on healthy participants have suggested that cerebellar
      transcranial direct current stimulation (tDCS) is a valuable tool to modulate
      cognitive functions. However, so far, only a single case study has investigated
      whether cerebellar stimulation enhances language recovery in aphasic individuals.
      In a randomized, crossover, double-blind design, we explored the effect of
      cerebellar tDCS coupled with language treatment for verb improvement in 12
      aphasic individuals. Each participant received cerebellar tDCS (20 min, 2 mA) in
      four experimental conditions: (1) right cathodal and (2) sham stimulation during
      a verb generation task and (3) right cathodal and (4) sham stimulation during a
      verb naming task. Each experimental condition was run in five consecutive daily
      sessions over 4 weeks. At the end of treatment, a significant improvement was
      found after cathodal stimulation only in the verb generation task. No significant
      differences were present for verb naming among the two conditions. We hypothesize
      that cerebellar tDCS is a viable tool for recovery from aphasia but only when the
      language task, such as verb generation, also demands the activation of
      nonlinguistic strategies.

PMID- 29064342
TI  - Quantitative Anatomical Evidence for a Dorsoventral and Rostrocaudal Segregation
      within the Nonhuman Primate Frontal Cortex.
AB  - The intrinsic white matter connections of the frontal cortex are highly complex,
      and the organization of these connections is not fully understood. Quantitative
      graph-theoretical methods, which are not solely reliant on human observation and
      interpretation, can be powerful tools for describing the organizing network
      principles of frontal cortex. Here, we examined the network structure of frontal
      cortical subregions by applying graph-theoretical community detection analyses to
      a graph of frontal cortex compiled from over 400+ macaque white-matter tracing
      studies. We find evidence that the lateral frontal cortex can be partitioned into
      distinct modules roughly organized along the dorsoventral and rostrocaudal axis.

PMID- 29064343
TI  - The Effect of Functional Movement Training After Anterior Cruciate Ligament
      Reconstruction: A Randomized Controlled Trial.
AB  - OBJECTIVES: To evaluate the effect of functional movement screen (FMS)-based
      functional exercise in patients after anterior cruciate ligament reconstruction
      (ACLR). DESIGN: Randomized, controlled, single-blind trial. SETTING:
      Institutional, single center. PATIENTS: A total of 38 patients who underwent ACLR
      were recruited and randomly assigned to group 1 (n = 19) or group 2 (n = 19).
      INTERVENTIONS: Both groups received 6-month routine rehabilitation immediately
      after surgery. From the postoperative fourth to sixth month, group 1 received FMS
      based functional exercise plus routine rehabilitation and group 2 received
      routine rehabilitation only. The FMS-based functional exercise was individualized
      and customized functional corrective exercise, which was designed based on the 3
      month postoperative FMS results. The frequency of rehabilitation was 1 hour per
      session, twice a week, for a total duration of 6 months. MAIN OUTCOME MEASURES:
      At 3 and 6 months postoperatively, patients were evaluated by FMS scoring,
      Lysholm Knee Score, and International Knee Documentation Committee 2000 Score.
      RESULTS: After the intervention, both groups had significantly increased FMS,
      Lysholm Knee Score, and International Knee Documentation Committee 2000 score.
      Group 1 had significantly greater changes in FMS (median: 4 vs 3, P < .001),
      Lysholm Knee Score (median: 24 vs 16, P = .001), and International Knee
      Documentation Committee 2000 Score (median: 22 vs 8, P < .001) than group 2.
      CONCLUSION: The application of FMS-based functional exercise to patients after
      ACLR resulted in significant improvement in knee function and movements. The
      authors suggested integrating FMS evaluation and FMS-based training into routine
      post-ACLR rehabilitation programs.

PMID- 29064341
TI  - The Role of Visual Association Cortex in Associative Memory Formation across
      Development.
AB  - Associative learning underlies the formation of new episodic memories.
      Associative memory improves across development, and this age-related improvement
      is supported by the development of the hippocampus and pFC. Recent work, however,
      additionally suggests a role for visual association cortex in the formation of
      associative memories. This study investigated the role of category-preferential
      visual processing regions in associative memory across development using a paired
      associate learning task in a sample of 56 youths (age 6-19 years). Participants
      were asked to bind an emotional face with an object while undergoing fMRI
      scanning. Outside the scanner, participants completed a memory test. We first
      investigated age-related changes in neural recruitment and found linear age
      related increases in activation in lateral occipital cortex and fusiform gyrus,
      which are involved in visual processing of objects and faces, respectively.
      Furthermore, greater activation in these visual processing regions was associated
      with better subsequent memory for pairs over and above the effect of age and of
      hippocampal and pFC activation on performance. Recruitment of these visual
      processing regions mediated the association between age and memory performance,
      over and above the effects of hippocampal activation. Taken together, these
      findings extend the existing literature to suggest that greater recruitment of
      category-preferential visual processing regions during encoding of associative
      memories is a neural mechanism explaining improved memory across development.

PMID- 29064344
TI  - Low Infection-Related Re-Admission Rates in a Retrospective of 4725 Children with
      Appendicitis Using a Clinical Pathway in a Tertiary Care Pediatric Center.
AB  - BACKGROUND: Standardization of antibiotic management of appendicitis in tertiary
      care pediatric centers has been associated with improved outcomes. Rady
      Children's Hospital-San Diego implemented an appendicitis clinical pathway in
      2005. We evaluated infection-related re-admission risk factors since 2010, when
      an electronic medical record was established, with the aim to optimize the
      clinical pathway. METHODS: Between January 2010 and August 2015, 4725 children
      with a diagnosis of appendicitis were evaluated for demographic data, pathology
      diagnoses, culture results, and inpatient and oral step-down antibiotic therapy
      regimens. From children originally admitted for appendicitis, those who were re
      admitted with infection were compared with those who were not re-admitted for
      infection. The populations were controlled by severity of infection using a
      pathology-defined appendicitis severity scale: Grade 0, no appendicitis; grade 1,
      simple acute appendicitis with gross and microscopic evidence of inflammation,
      but no perforation; grade 2, gangrenous/necrotizing/micro-perforated appendicitis
      with subserosal or serosal exudate, but no frank or visually appreciated
      perforation; and grade 3, frank perforation. RESULTS: Of 4725 children (total
      population, TP) admitted with a diagnosis of appendicitis, only 199 (4.2%) were
      re-admitted, with 125 of these admissions for infection (2.65% of the TP). Age,
      race/ethnicity, language preference, and body mass index were not found to
      correlate with re-admission for infection. Length of stay significantly differed
      between the no infection-related re-admission population and infection-related re
      admission population (3.02 vs. 4.03 d, p < 0.001). There was a trend toward
      higher infection-re-admission rates as the pathology grade increased (odds ratio
      grade 1 vs. grade 3 = 2.28, 95% confidence interval 1.03, 5.03). CONCLUSIONS:
      Infection-related re-admission rates for children on the clinical pathway in our
      institution were infrequent. The greater association of all-cause and infection
      related re-admission rates with pathology grade suggest that defining
      appendicitis by pathology and clinical severity may provide an evidence-based
      scoring system to support clinical observation in the use and duration of
      antibiotic therapy.

PMID- 29064345
TI  - Need for Comprehensive Health Care Quality Measures for Older Adults.
AB  - Research indicates that older adults receive only about half of their recommended
      care, with varying quality and limited attention to social issues impacting their
      health through the most commonly used quality measures. Additionally, many
      existing measures neglect to address nonclinical social determinants of health.
      Evidence of the need for more comprehensive measures for seniors is growing. The
      primary purpose of this article, which is supported by a limited review of
      literature, is to describe gaps among current quality measures in addressing
      certain nonclinical needs of older adults, including key social determinants of
      health. In doing so, the authors describe their position on the need for expanded
      measures to incorporate these factors to improve care and quality of life. The
      authors conducted a limited review of the literature to inform this article,
      focusing specifically on selected measures for older adults rather than a broader
      systematic review of all measures. Most research identified was related to
      clinical practice guidelines rather than quality measures of care as applied to
      older adults. Furthermore, the literature reviewed reflected limited evidence of
      efforts to tailor quality measures for the unique social needs of older adults,
      confirming a potential gap in this area. A growing need exists for improved
      quality measures specifically designed to help providers address the unique
      social needs of older adults. Filling this gap will improve overall understanding
      of seniors and help them to achieve optimal health and successful aging.

PMID- 29064346
TI  - Metabolic counterparts of sodium accumulation in multiple sclerosis: A whole
      brain 23Na-MRI and fast 1H-MRSI study.
AB  - BACKGROUND: Increase of brain total sodium concentrations (TSC) is present in
      multiple sclerosis (MS), but its pathological involvement has not been assessed
      yet. OBJECTIVE: To determine in vivo the metabolic counterpart of brain sodium
      accumulation. MATERIALS/METHODS: Whole brain 23Na-MR imaging and 3D-1H-EPSI data
      were collected in 21 relapsing-remitting multiple sclerosis (RRMS) patients and
      20 volunteers. Metabolites and sodium levels were extracted from several regions
      of grey matter (GM), normal-appearing white matter (NAWM) and white matter (WM)
      T2 lesions. Metabolic and ionic levels expressed as Z-scores have been averaged
      over the different compartments and used to explain sodium accumulations through
      stepwise regression models. RESULTS: MS patients showed significant 23Na
      accumulations with lower choline and glutamate-glutamine (Glx) levels in GM; 23Na
      accumulations with lower N-acetyl aspartate (NAA), Glx levels and higher Myo
      Inositol (m-Ins) in NAWM; and higher 23Na, m-Ins levels with lower NAA in WM T2
      lesions. Regression models showed associations of TSC increase with reduced NAA
      in GM, NAWM and T2 lesions, as well as higher total-creatine, and smaller
      decrease of m-Ins in T2 lesions. GM Glx levels were associated with clinical
      scores. CONCLUSION: Increase of TSC in RRMS is mainly related to neuronal
      mitochondrial dysfunction while dysfunction of neuro-glial interactions within GM
      is linked to clinical scores.

PMID- 29064347
TI  - Excess mortality in Italy: Should we care about low influenza vaccine uptake?
AB  - AIMS: The aims of this study were to explore 2015 mortality data further and to
      assess excess deaths' determinants. METHODS: We analysed data from a large
      metropolitan area in the north of Italy, the city of Bologna. We took advantage
      of a comprehensive local-level database and merged three different data sources
      to analitically explore reported 2014-2015 excess mortality and its determinants.
      Effect estimates were derived from multivariable Poisson regression analysis,
      according to vaccination status and frailty index. RESULTS: We report 9.8% excess
      mortality in 2015 compared to 2014, with seasonal and age distribution patterns
      in line with national figures. All-cause mortality in the elderly population is
      36% higher (risk ratio [RR]=1.36, 95% confidence interval [CI] 1.27-1.45) in
      subjects not vaccinated against seasonal flu compared to vaccinated subjects,
      with risk of death for influenza or pneumonia being 43% higher (RR=1.43, 95% CI
      1.02-2.00) in unvaccinated subjects. CONCLUSIONS: Reported excess mortality's
      determinants in Italy should be further explored. Elderly subjects not vaccinated
      against the flu appear to have increased risk of all-cause and cause-specific
      mortality compared to vaccinated subjects after accounting for possible
      confounders. Our findings raise awareness of the need to promote immunisation
      against the flu among elder populations and offer insights to plan and implement
      effective public-health interventions.

PMID- 29064348
TI  - The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing
      Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single
      Center Study Over a Period of 12 Years.
AB  - Despite global efforts to tackle resistance in extended-spectrum beta-lactamase
      (ESBL)-producing isolates via old antibiotics, there are limited data on the
      efficacy of fosfomycin-an old oral antibiotic-against Enterobacteriaceae in the
      Middle East. The purpose of this study was to evaluate the in vitro activity of
      fosfomycin against urinary ESBL-producing isolates of Enterobacteriaceae. Between
      2004 and 2015, 363 isolates of ESBL-producing Enterobacteriaceae were recovered
      from high-risk patients suffering from cardiac disorders and were subjected to
      polymerase chain reaction using specific primers for the blaTEM, blaSHV, and
      blaCTX-M genes. Antibiotic susceptibility testing was performed for fosfomycin
      and other antibiotic comparators. For the isolates considered nonsusceptible to
      fosfomycin by disk diffusion, the minimum inhibitory concentration (MIC) was
      determined. The susceptibility rate to fosfomycin remained almost steady (90
      100%) over a 12-year period, although it fluctuated vis-a-vis ciprofloxacin (0
      54%), trimethoprim/sulfamethoxazole (9.1-31.7%), and nitrofurantoin (41.7-100%).
      Of all the antibiotics tested, fosfomycin was the most active antimicrobial agent
      (97%) against the ESBL-positive isolates. Fosfomycin maintained higher activity
      against ESBL-Escherichia coli than against ESBL-Klebsiella pneumoniae. Only 11
      (3%) isolates were not susceptible to fosfomycin according to disk diffusion and
      they had MICs greater than 1,024 mg/ml. All of the fosfomycin-nonsusceptible
      isolates were positive for the blaCTX-M gene (100%), while 5 (45.4%) and 3
      (27.3%) of the isolates harbored the blaTEM and blaSHV genes, respectively. We
      showed that fosfomycin had a numerically higher susceptibility rate than the
      other antibiotics against the ESBL-producing isolates of the most common
      Enterobacteriaceae. Given its low resistance rate and oral administration,
      fosfomycin may be deemed a promising antibiotic for the treatment of urinary
      tract infections caused by ESBL-producing Enterobacteriaceae.

PMID- 29064350
TI  - Patenting the microbiome: trends, challenges and insights.

PMID- 29064349
TI  - Bosentan-based, treat-to-target therapy in patients with pulmonary arterial
      hypertension: results from the COMPASS-3 study.
AB  - The phase 4 COMPASS-3 study evaluated whether a singular endpoint produces
      clinically meaningful outcomes in patients with pulmonary arterial hypertension
      (PAH). The relationship between cardiac magnetic resonance imaging (cMRI)-derived
      parameters and right heart catheterization (RHC) measurements was also examined.
      In COMPASS-3 (ClinicalTrials.gov NCT00433329), 100 patients with PAH received
      bosentan monotherapy for 16 weeks. Patients continued monotherapy if their 6-min
      walk distance (6MWD) was >=380 m, or otherwise received add-on sildenafil for an
      additional 12 weeks. 6MWD, RHC, and cMRI were performed at baseline, week 16, and
      week 28 (6MWD and cMRI). Baseline median 6MWD was 274 m and 82% of patients had
      WHO Functional Class III/IV. At week 16, 17% (n = 16) of remaining patients
      achieved the 6MWD threshold and 78 (83%) did not. In the intention-to-treat
      population, median 6MWD increased significantly relative to baseline (week 16 =
      308 m; week 28 = 327 m; P < 0.001). At week 28, 9/16 (monotherapy) and 15/76
      (20%; add-on sildenafil) patients met the target threshold. Baseline cMRI-derived
      and RHC-derived parameters showed moderate-to-strong correlations (e.g. right to
      left ventricular end-diastolic ratio [RVEDV:LVEDV] correlated strongly with
      pulmonary vascular resistance [r = +0.729, P < 0.0001]). cMRI-derived parameters
      predicted clinical worsening/decline (e.g. week 16 RVEDV:LVDEV [ P = 0.0172]).
      Time to clinical worsening/decline did not differ between patients based on 6MWD
      threshold achievement. No unexpected safety events were reported. A substantial
      proportion of patients failed to achieve the goal of 380 m, regardless of
      treatment. Several cMRI parameters predicted clinical worsening/decline and its
      non-invasive nature further supports its use in future clinical trials.

PMID- 29064351
TI  - Mechanisms and Factors That Drive Extensive Human Immunodeficiency Virus Type-1
      Hypervariability: An Overview.
AB  - The extensive hypervariability of human immunodeficiency virus type-1 (HIV-1)
      populations represents a major barrier against the success of currently available
      antiretroviral therapy. Moreover, it is still the most important obstacle that
      faces the development of an effective preventive vaccine against this infectious
      virus. Indeed, several factors can drive such hypervariability within and between
      HIV-1 patients. These factors include: first, the very low fidelity nature of HIV
      1 reverse transcriptase; second, the extremely high HIV-1 replication rate; and
      third, the high genomic recombination rate that the virus has. All these factors
      together with the APOBEC3 proteins family and the immune and antiviral drugs
      pressures drive the extensive hypervariability of HIV-1 populations. Studying
      these factors and the mechanisms that drive such hypervariability will provide
      valuable insights that may guide the development of effective therapeutic and
      preventive strategies against HIV-1 infection in the near future. To this end, in
      this review, we summarized recent advances in this area of HIV-1 research.

PMID- 29064352
TI  - Seroprevalence of Anti-Toxoplasma gondii Antibodies Among Lebanese Pregnant
      Women.
AB  - OBJECTIVE: Toxoplasma gondii, the causative agent of toxoplasmosis, is a zoonotic
      obligate intracellular protozoan parasite responsible for the infection of almost
      one-third of the world's population. T. gondii is particularly threatening for
      primo-infected pregnant women and may lead, following vertical transplacental
      transmission, to spontaneous abortion, miscarriage, or severe manifestations in
      the newborn. The aim of this study was to provide an updated estimate of the
      seroprevalence of anti-T. gondii antibodies among a group of Lebanese pregnant
      women and its seroconversion rate. METHODS: This is a retrospective cohort study,
      in which medical records of 11,000 pregnant women were screened. These women
      visited a private Obstetrics and Gynecology clinic located in Beirut, the capital
      of Lebanon, during the period of January 1994 till September 2015. Serological
      results of anti-T. gondii immunoglobulin G (IgG) and immunoglobulin M (IgM)
      results of 2456 Lebanese pregnant women who fulfilled the inclusion criteria were
      included in the analysis. Seropositivity and seroconversion rates for women with
      repeated tests were reported according to age and area of residence. RESULTS: The
      overall anti-T. gondii IgG and IgM seropositivity among 2456 Lebanese pregnant
      women was 82.6% and 1.8% respectively. The highest IgG seropositivity is among
      the age group of 35-44 years (87.81%) and at the governorate of "Mount Lebanon"
      (82.95%). Sixty-four seroconversions were detected and two abortions due to T.
      gondii infection during pregnancy were recorded. CONCLUSIONS: The seroprevalence
      of anti-T. gondii IgG among the screened pregnant women in Lebanon is the highest
      in the Arab region. These results highlight the importance of running a national
      sample survey to estimate the real potential burden of this infection and its
      impact on maternal and fetal health.

PMID- 29064353
TI  - Dual ETA/ETB blockade with macitentan improves both vascular remodeling and
      angiogenesis in pulmonary arterial hypertension.
AB  - Dysregulated metabolism and rarefaction of the capillary network play a critical
      role in pulmonary arterial hypertension (PAH) etiology. They are associated with
      a decrease in perfusion of the lungs, skeletal muscles, and right ventricle (RV).
      Previous studies suggested that endothelin-1 (ET-1) modulates both metabolism and
      angiogenesis. We hypothesized that dual ETA/ETB receptors blockade improves PAH
      by improving cell metabolism and promoting angiogenesis. Five weeks after disease
      induction, Sugen/hypoxic rats presented severe PAH with pulmonary artery (PA)
      remodeling, RV hypertrophy and capillary rarefaction in the lungs, RV, and
      skeletal muscles (microCT angiogram, lectin perfusion, CD31 staining). Two-week
      treatment with dual ETA/ETB receptors antagonist macitentan (30 mg/kg/d)
      significantly improved pulmonary hemodynamics, PA vascular remodeling, and RV
      function and hypertrophy compared to vehicle-treated animals (all P = 0.05).
      Moreover, macitentan markedly increased lung, RV and quadriceps perfusion, and
      microvascular density (all P = 0.05). In vitro, these effects were associated
      with increases in oxidative phosphorylation (oxPhox) and markedly reduced cell
      proliferation of PAH-PA smooth muscle cells (PASMCs) treated with macitentan
      without affecting apoptosis. While macitentan did not affect oxPhox,
      proliferation, and apoptosis of PAH-PA endothelial cells (PAECs), it
      significantly improved their angiogenic capacity (tube formation assay). Exposure
      of control PASMC and PAEC to ET-1 fully mimicked the PAH cells phenotype, thus
      confirming that ET-1 is implicated in both metabolism and angiogenesis
      abnormalities in PAH. Dual ETA/ETB receptor blockade improved the metabolic
      changes involved in PAH-PASMCs' proliferation and the angiogenic capacity of PAH
      PAEC leading to an increased capillary density in lungs, RV, and skeletal
      muscles.

PMID- 29064354
TI  - Building and Rebuilding: The National Public Health Laboratory Systems and
      Services Before and After the Earthquake and Cholera Epidemic, Haiti, 2009-2015.
AB  - Before the 2010 devastating earthquake and cholera outbreak, Haiti's public
      health laboratory systems were weak and services were limited. There was no
      national laboratory strategic plan and only minimal coordination across the
      laboratory network. Laboratory capacity was further weakened by the destruction
      of over 25 laboratories and testing sites at the departmental and peripheral
      levels and the loss of life among the laboratory health-care workers. However,
      since 2010, tremendous progress has been made in building stronger laboratory
      infrastructure and training a qualified public health laboratory workforce across
      the country, allowing for decentralization of access to quality-assured services.
      Major achievements include development and implementation of a national
      laboratory strategic plan with a formalized and strengthened laboratory network;
      introduction of automation of testing to ensure better quality of results and
      diversify the menu of tests to effectively respond to outbreaks; expansion of
      molecular testing for tuberculosis, human immunodeficiency virus, malaria,
      diarrheal and respiratory diseases; establishment of laboratory-based
      surveillance of epidemic-prone diseases; and improvement of the overall quality
      of testing. Nonetheless, the progress and gains made remain fragile and require
      the full ownership and continuous investment from the Haitian government to
      sustain these successes and achievements.

PMID- 29064355
TI  - Assessment of Drinking Water Sold from Private Sector Kiosks in Post-Earthquake
      Port-au-Prince, Haiti.
AB  - Consumption of drinking water from private vendors has increased considerably in
      Port-au-Prince, Haiti, in recent decades. A major type of vendor is private
      kiosks, advertising reverse osmosis-treated water for sale by volume. To describe
      the scale and geographical distribution of private kiosks in metropolitan Port-au
      Prince, an inventory of private kiosks was conducted from July to August 2013.
      Coordinates of kiosks were recorded with global positioning system units and a
      brief questionnaire was administered with the operator to document key kiosk
      characteristics. To assess the quality of water originating from private kiosks,
      water quality analyses were also conducted on a sample of those inventoried as
      well as from the major provider company sites. The parameters tested were
      Escherichia coli, free chlorine residual, pH, turbidity, and total dissolved
      solids. More than 1,300 kiosks were inventoried, the majority of which were
      franchises of four large provider companies. Approximately half of kiosks
      reported opening within 12 months of the date of the inventory. The kiosk
      treatment chain and sales price was consistent among a majority of the kiosks. Of
      the 757 kiosks sampled for water quality, 90.9% of samples met World Health
      Organization (WHO) microbiological guideline at the point of sale for
      nondetectable E. coli in a 100-mL sample. Of the eight provider company sites
      tested, all samples met the WHO microbiological guideline. Because of the
      increasing role of the private sector in drinking water provision in Port-au
      Prince and elsewhere in Haiti, this assessment was an important first step for
      government regulation of this sector.

PMID- 29064356
TI  - Expansion of Vaccination Services and Strengthening Vaccine-Preventable Diseases
      Surveillance in Haiti, 2010-2016.
AB  - Following the 2010 earthquake, Haiti was at heightened risk for vaccine
      preventable diseases (VPDs) outbreaks due to the exacerbation of long-standing
      gaps in the vaccination program and subsequent risk of VPD importation from other
      countries. Therefore, partners supported the Haitian Ministry of Health and
      Population to improve vaccination services and VPD surveillance. During 2010
      2016, three polio, measles, and rubella vaccination campaigns were implemented,
      achieving a coverage > 90% among children and maintaining Haiti free of those
      VPDs. Furthermore, Haiti is on course to eliminate maternal and neonatal tetanus,
      with 70% of communes achieving tetanus vaccine two-dose coverage > 80% among
      women of childbearing age. In addition, the vaccine cold chain storage capacity
      increased by 91% at the central level and 285% at the department level, enabling
      the introduction of three new vaccines (pentavalent, rotavirus, and pneumococcal
      conjugate vaccines) that could prevent an estimated 5,227 deaths annually. Haiti
      moved from the fourth worst performing country in the Americas in 2012 to the
      sixth best performing country in 2015 for adequate investigation of suspected
      measles/rubella cases. Sentinel surveillance sites for rotavirus diarrhea and
      meningococcal meningitis were established to estimate baseline rates of those
      diseases prior to vaccine introduction and to evaluate the impact of vaccination
      in the future. In conclusion, Haiti significantly improved vaccination services
      and VPD surveillance. However, high dependence on external funding and competing
      vaccination program priorities are potential threats to sustaining the
      improvements achieved thus far. Political commitment and favorable economic and
      legal environments are needed to maintain these gains.

PMID- 29064358
TI  - Public Health Progress in Haiti.

PMID- 29064357
TI  - Retention Throughout the HIV Care and Treatment Cascade: From Diagnosis to
      Antiretroviral Treatment of Adults and Children Living with HIV-Haiti, 1985-2015.
AB  - Monitoring retention of people living with HIV (PLHIV) in the HIV care and
      treatment cascade is essential to guide program strategy and evaluate progress
      toward globally-endorsed 90-90-90 targets (i.e., 90% of PLHIV diagnosed, 81% on
      sustained antiretroviral therapy (ART), and 73% virally suppressed). We describe
      national retention from diagnosis throughout the cascade for patients receiving
      HIV services in Haiti during 1985-2015, with a focus on those receiving HIV
      services during 2008-2015. Among the 266,256 newly diagnosed PLHIV during 1985
      2015, 49% were linked-to-care, 30% started ART, and 18% were retained on ART by
      the time of database closure. Similarly, among the 192,187 newly diagnosed HIV
      positive patients during 2008-2015, 50% were linked to care, 31% started ART, and
      19% were retained on ART by the time of database closure. Most patients (90-92%)
      at all cascade steps were adults (>= 15 years old), among whom the majority (60
      61%) were female. During 2008-2015, outcomes varied significantly across 42
      administrative districts (arrondissements) of residence; cumulative linkage-to
      care ranged from 23% to 69%, cumulative ART initiation among care enrollees
      ranged from 2% to 80%, and cumulative ART retention among ART enrollees ranged
      from 30% to 88%. Compared with adults, children had lower cumulative incidence of
      ART initiation among care enrollees (64% versus 47%) and lower cumulative
      retention among ART enrollees (64% versus 50%). Cumulative linkage-to-care was
      low and should be prioritized for improvement. Variations in outcomes by
      arrondissement and between adults and children require further investigation and
      programmatic response.

PMID- 29064359
TI  - Applying a New Framework for Public Health Systems Recovery following Emergencies
      and Disasters: The Example of Haiti following a Major Earthquake and Cholera
      Outbreak.
AB  - Emergencies can often directly impact health systems of an affected region or
      country, especially in resource-constrained areas. Health system recovery
      following an emergency is a complex and dynamic process. Health system recovery
      efforts have often been structured around the World Health Organization's health
      systems building blocks as demonstrated by the Post-Disaster Needs Assessment.
      Although this structure is valuable and well known, it can overlook the
      intricacies of public health systems. We retrospectively examine public health
      systems recovery, a subset of the larger health system, following the 2010 Haiti
      earthquake and cholera outbreak, through the lens of the 10 essential public
      health services. This framework illustrates the comprehensive nature of and helps
      categorize the activities necessary for a well-functioning public health system
      and can complement other assessments. Outlining the features of a public health
      system for recovery in structured manner can also help lay the foundation for
      sustainable long-term development leading to a more robust and resilient health
      system.

PMID- 29064360
TI  - Haiti's Commitment to Malaria Elimination: Progress in the Face of Challenges,
      2010-2016.
AB  - Haiti is committed to malaria elimination by 2020. Following a 2010 earthquake
      and cholera epidemic, Haiti capitalized on investments in its health system to
      refocus on malaria elimination. Efforts, including expanding diagnostics,
      ensuring efficacy of standard treatments, building institutional capacity, and
      strengthening surveillance were undertaken to complement the broad health system
      strengthening activities. These efforts led to the adoption and scale-up of
      malaria rapid diagnostic tests as a diagnostic modality. In addition, drug
      resistant monitoring has been established in the country, along with the
      development of molecular testing capacity for the Plasmodium falciparum parasite
      at the National Public Health Laboratory. The development and piloting of
      surveillance activities to include an enhanced community-based approach for
      testing and treatment of patients has increased the ability of the Ministry of
      Health to map foci of transmission and respond promptly to outbreaks. The
      reinforcement of evidence-based approaches coupled with strong collaboration
      among the Ministry of Health and partners has demonstrated that malaria
      elimination by 2020 is a realistic prospect.

PMID- 29064361
TI  - Strengthening National Disease Surveillance and Response-Haiti, 2010-2015.
AB  - Haiti's health system has faced many challenges over the years, with competing
      health priorities in the context of chronic financial and human resource
      limitations. As a result, the existing notifiable disease surveillance system was
      unable to provide the most basic epidemiologic data for public health decision
      making and action. In the wake of the January 2010 earthquake, the Haitian
      Ministry of Public Health and Population collaborated with the U.S. Centers for
      Disease Control and Prevention, the Pan American Health Organization, and other
      local and international partners to implement a functional national surveillance
      system. More than 7 years later, it is important to take the opportunity to
      reflect on progress made on surveillance and response in Haiti, including disease
      detection, reporting, outbreak investigation, and response. The national
      epidemiologic surveillance network that started with 51 sites in 2010 has been
      expanded to 357 sites as of December 2015. Disease outbreaks identified via the
      surveillance system, or other surveillance approaches, are investigated by
      epidemiologists trained by the Ministry of Health's Field Epidemiology Training
      Program. Other related surveillance modules have been developed on the same model
      and electronic platform, allowing the country to document the impact of
      interventions, track progress, and monitor health problems. Sustainability
      remains the greatest challenge since most of the funding for surveillance come
      from external sources.

PMID- 29064362
TI  - Cost Evaluation of a Government-Conducted Oral Cholera Vaccination Campaign
      Haiti, 2013.
AB  - The devastating 2010 cholera epidemic in Haiti prompted the government to
      introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We
      evaluated the direct costs associated with the government's first vaccine
      campaign implemented in August-September 2013. We analyzed data for major cost
      categories and assessed the efficiency of available campaign resources to
      vaccinate the target population. For a target population of 107,906 persons,
      campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total
      vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per
      dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and
      transport $0.35 per dose. Resources were greater than needed-our analyses
      suggested that approximately 2.5-6 times as many persons could have been
      vaccinated during this campaign without increasing the resources allocated for
      vaccine delivery and administration. These results can inform future OCV
      campaigns in Haiti.

PMID- 29064363
TI  - The Health Impact of Rabies in Haiti and Recent Developments on the Path Toward
      Elimination, 2010-2015.
AB  - Haiti, a Caribbean country of 10.5 million people, is estimated to have the
      highest burden of canine-mediated human rabies deaths in the Western Hemisphere,
      and one of the highest rates of human rabies deaths in the world. Haiti is also
      the poorest country in the Western Hemisphere and has numerous economic and
      health priorities that compete for rabies-control resources. As a result, primary
      rabies-control actions, including canine vaccination programs, surveillance
      systems for human and animal rabies, and appropriate postbite treatment, have not
      been fully implemented at a national scale. After the 2010 earthquake that
      further hindered the development of public health program infrastructure and
      services, the U.S. Centers for Disease Control and Prevention worked with the
      Ministry of Public Health and Population and key health development partners
      (including the Pan-American Health Organization) to provide technical expertise
      and funding for general disease surveillance systems, laboratory capacity, and
      selected disease control programs; including rabies. In 2011, a cross-ministerial
      rabies consortium was convened with participation from multiple international
      rabies experts to develop a strategy for successful rabies control in Haiti. The
      consortium focused on seven pillars: 1) enhancement of laboratory diagnostic
      capacity, 2) development of comprehensive animal surveillance system, 3)
      development of comprehensive human rabies surveillance system, 4) educational
      outreach, 5) sustainable human rabies biologics supply, 6) achievement of
      sustained canine vaccination rates of >= 70%, and 7) finalization of a national
      rabies control strategy. From 2010 until 2015, Haiti has seen improvements in the
      program infrastructure for canine rabies control. The greatest improvements were
      seen in the area of animal rabies surveillance, in support of which an
      internationally recognized rabies laboratory was developed thereby leading to an
      18-fold increase in the detection of rabid animals. Canine rabies vaccination
      practices also improved, from a 2010 level of approximately 12% to a 2015 dog
      population coverage level estimated to be 45%. Rabies vaccine coverage is still
      below the goal of 70%, however, the positive trend is encouraging. Gaps exist in
      the capacity to conduct national surveillance for human rabies cases and access
      to human rabies vaccine is lacking in many parts of the country. However, control
      has improved over the past 5 years as a result of the efforts of Haiti's health
      and agriculture sectors with assistance from multiple international
      organizations. Haiti is well situated to eliminate canine-mediated human rabies
      deaths in the near future and should serve as a great example to many developing
      countries struggling with similar barriers and limitations.

PMID- 29064364
TI  - Translating Research into Reality: Elimination of Lymphatic Filariasis from
      Haiti.
AB  - Research provides the essential foundation of disease elimination programs,
      including the global program to eliminate lymphatic filariasis (GPELF). The
      development and validation of new diagnostic tools and intervention strategies,
      critical steps in the evolution of GPELF, required a global effort. Lymphatic
      filariasis research in Haiti involved many partners and was directly linked to
      the development of the national elimination program and to the success achieved
      to date. Ongoing research efforts involving many partners will continue to be
      important in resolving the challenges faced by the program today in its final
      efforts to achieve elimination.

PMID- 29064365
TI  - Trends in Tuberculosis Case Notification and Treatment Success, Haiti, 2010-2015.
AB  - Since the 2010 earthquake, tuberculosis (TB) control has been a major priority
      for health sector response and recovery efforts in Haiti. The goal of this study
      was to analyze trends in TB case notification in Haiti from the aggregate data
      reported by the National TB Control Program to understand the effects of such
      efforts. A total of 95,745 TB patients were registered for treatment in Haiti
      between 2010 and 2015. Three regions, the West, Artibonite, and North departments
      accounted for 68% of the TB cases notified during the period. Patients in the 15
      34 age groups represented 53% (50,560) of all cases. Case notification rates of
      all forms of TB increased from 142.7/100,000 in 2010 to 153.4 in 2015, peaking at
      163.4 cases/100,000 in 2013. Case notification for smear-positive pulmonary TB
      increased from 85.5 cases/100,000 to 105.7 cases/100,000, whereas treatment
      success rates remained stable at 79-80% during the period. Active TB case finding
      efforts in high-risk communities and the introduction of new diagnostics have
      contributed to increasing TB case notification trends in Haiti from 2010 to 2015.
      Targeted interventions and novel strategies are being implemented to reach high
      risk populations and underserved communities.

PMID- 29064366
TI  - Spot protein-creatinine ratio and spot albumin-creatinine ratio in the assessment
      of pre-eclampsia: a diagnostic accuracy study with decision-analytic model-based
      economic evaluation and acceptability analysis.
AB  - BACKGROUND: The National Institute for Health and Care Excellence (NICE)
      guidelines highlighted the need for 'large, high-quality prospective studies
      comparing the various methods of measuring proteinuria in women with new-onset
      hypertensive disorders during pregnancy'. OBJECTIVES: The primary objective was
      to evaluate quantitative assessments of spot protein-creatinine ratio (SPCR) and
      spot albumin-creatinine ratio (SACR) in predicting severe pre-eclampsia (PE)
      compared with 24-hour urine protein measurement. The secondary objectives were to
      investigate interlaboratory assay variation, to evaluate SPCR and SACR thresholds
      in predicting adverse maternal and fetal outcomes and to assess the cost
      effectiveness of these models. DESIGN: This was a prospective diagnostic accuracy
      cohort study, with decision-analytic modelling and a cost-effectiveness analysis.
      SETTING: The setting was 36 obstetric units in England, UK. PARTICIPANTS:
      Pregnant women (aged >= 16 years), who were at > 20 weeks' gestation with
      confirmed gestational hypertension and trace or more proteinuria on an automated
      dipstick urinalysis. INTERVENTIONS: Women provided a spot urine sample for
      protein analysis (the recruitment sample) and were asked to collect a 24-hour
      urine sample, which was stored for secondary analysis. A further spot sample of
      urine was taken immediately before delivery. MAIN OUTCOME MEASURES: Outcome data
      were collected from hospital records. There were four index tests on a spot
      sample of urine: (1) SPCR test (conducted at the local laboratory); (2) SPCR test
      [conducted at the central laboratory using the benzethonium chloride (BZC)
      assay]; (3) SPCR test [conducted at the central laboratory using the pyrogallol
      red (PGR) assay]; and (4) SACR test (conducted at the central laboratory using an
      automated chemistry analyser). The comparator tests on 24-hour urine collection
      were a central test using the BZC assay and a central test using the PGR assay.
      The primary reference standard was the NICE definition of severe PE. Secondary
      reference standards were a clinician diagnosis of severe PE, which is defined as
      treatment with magnesium sulphate or with severe PE protocol; adverse perinatal
      outcome; one or more of perinatal or infant mortality, bronchopulmonary
      dysplasia, necrotising enterocolitis or grade III/IV intraventricular
      haemorrhage; and economic cost and outcomes. Health service data on service use
      and costs followed published economic models. RESULTS: In total, 959 women were
      available for primary analysis and 417 of them had severe PE. The diagnostic
      accuracy of the four assays on spot urine samples against the reference standards
      was similar. The three SPCR tests had sensitivities in excess of 90% at
      prespecified thresholds, with poor specificities and negative likelihood ratios
      of >= 0.1. The SACR test had a significantly higher sensitivity of 99%
      (confidence interval 98% to 100%) and lower specificity. Receiver operating
      characteristic (ROC) curves were similar (area under ROC curve between 0.87 and
      0.89); the area under the central laboratory's SACR curve was significantly
      higher (p = 0.004). The central laboratory's SACR test was the most cost
      effective option, generating an additional 0.03 quality-adjusted life-years at an
      additional cost of L45.07 compared with the local laboratory's SPCR test. The
      probabilistic analysis showed it to have a 100% probability of being cost
      effective at the standard willingness-to-pay threshold recommended by NICE.
      LIMITATIONS: Implementation of NICE guidelines has led to an increased
      intervention rate in the study population that affected recruitment rates and led
      to revised sample size calculations. CONCLUSIONS: Evidence from this clinical
      study does not support the recommendation of 24-hour urine sample collection in
      hypertensive pregnant women. The SACR test had better diagnostic performance when
      predicting severe pre-eclampsia. All four tests could potentially be used as rule
      out tests for the NICE definition of severe PE. FUTURE WORK: Testing SACR at a
      threshold of 8 mg/mmol should be studied as a 'rule-out' test of proteinuria.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN82607486. FUNDING: This
      project was funded by the National Institute Health Research (NIHR) Health
      Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 21, No. 61. See the NIHR Journals Library website for
      further project information.

PMID- 29064367
TI  - Cross-species functional diversity within the PIN auxin efflux protein family.
AB  - In Arabidopsis, development during flowering is coordinated by transport of the
      hormone auxin mediated by polar-localized PIN-FORMED1 (AtPIN1). However
      Arabidopsis has lost a PIN clade sister to AtPIN1, Sister-of-PIN1 (SoPIN1), which
      is conserved in flowering plants. We previously proposed that the AtPIN1 organ
      initiation and vein patterning functions are split between the SoPIN1 and PIN1
      clades in grasses. Here we show that in the grass Brachypodium sopin1 mutants
      have organ initiation defects similar to Arabidopsis atpin1, while loss of PIN1
      function in Brachypodium has little effect on organ initiation but alters stem
      growth. Heterologous expression of Brachypodium SoPIN1 and PIN1b in Arabidopsis
      provides further evidence of functional specificity. SoPIN1 but not PIN1b can
      mediate flower formation in null atpin1 mutants, although both can complement a
      missense allele. The behavior of SoPIN1 and PIN1b in Arabidopsis illustrates how
      membrane and tissue-level accumulation, transport activity, and interaction
      contribute to PIN functional specificity.

PMID- 29064370
TI  - Stability analysis of a deterministic dose calculation for MRI-guided
      radiotherapy.
AB  - Modern effort in radiotherapy to address the challenges of tumor localization and
      motion has led to the development of MRI guided radiotherapy technologies.
      Accurate dose calculations must properly account for the effects of the MRI
      magnetic fields. Previous work has investigated the accuracy of a deterministic
      linear Boltzmann transport equation (LBTE) solver that includes magnetic field,
      but not the stability of the iterative solution method. In this work, we perform
      a stability analysis of this deterministic algorithm including an investigation
      of the convergence rate dependencies on the magnetic field, material density,
      energy, and anisotropy expansion. The iterative convergence rate of the
      continuous and discretized LBTE including magnetic fields is determined by
      analyzing the spectral radius using Fourier analysis for the stationary source
      iteration (SI) scheme. The spectral radius is calculated when the magnetic field
      is included (1) as a part of the iteration source, and (2) inside the streaming
      collision operator. The non-stationary Krylov subspace solver GMRES is also
      investigated as a potential method to accelerate the iterative convergence, and
      an angular parallel computing methodology is investigated as a method to enhance
      the efficiency of the calculation. SI is found to be unstable when the magnetic
      field is part of the iteration source, but unconditionally stable when the
      magnetic field is included in the streaming-collision operator. The discretized
      LBTE with magnetic fields using a space-angle upwind stabilized discontinuous
      finite element method (DFEM) was also found to be unconditionally stable, but the
      spectral radius rapidly reaches unity for very low-density media and increasing
      magnetic field strengths indicating arbitrarily slow convergence rates. However,
      GMRES is shown to significantly accelerate the DFEM convergence rate showing only
      a weak dependence on the magnetic field. In addition, the use of an angular
      parallel computing strategy is shown to potentially increase the efficiency of
      the dose calculation.

PMID- 29064368
TI  - AMPylation targets the rate-limiting step of BiP's ATPase cycle for its
      functional inactivation.
AB  - The endoplasmic reticulum (ER)-localized Hsp70 chaperone BiP contributes to
      protein folding homeostasis by engaging unfolded client proteins in a process
      that is tightly coupled to ATP binding and hydrolysis. The inverse correlation
      between BiP AMPylation and the burden of unfolded ER proteins suggests a post
      translational mechanism for adjusting BiP's activity to changing levels of ER
      stress, but the underlying molecular details are unexplored. We present
      biochemical and crystallographic studies indicating that irrespective of the
      identity of the bound nucleotide AMPylation biases BiP towards a conformation
      normally attained by the ATP-bound chaperone. AMPylation does not affect the
      interaction between BiP and J-protein co-factors but appears to allosterically
      impair J protein-stimulated ATP-hydrolysis, resulting in the inability of
      modified BiP to attain high affinity for its substrates. These findings suggest a
      molecular mechanism by which AMPylation serves as a switch to inactivate BiP,
      limiting its interactions with substrates whilst conserving ATP.

PMID- 29064371
TI  - Emission dynamics of hybrid plasmonic gold/organic GaN nanorods.
AB  - We studied the emission of bare and aluminum quinoline (Alq3)/gold coated
      wurtzite GaN nanorods by temperature- and intensity-dependent time-integrated and
      time-resolved photoluminescence (PL). The GaN nanorods of ~1.5 MUm length and
      ~250 nm diameter were grown by plasma-assisted molecular beam epitaxy. Gold/Alq3
      coated GaN nanorods were synthesized by organic molecular beam deposition. The
      near band-edge and donor-acceptor pair luminescence was investigated in bare GaN
      nanorods and compared with multilevel model calculations providing the dynamical
      parameters for electron-hole pairs, excitons, impurity bound excitons, donors and
      acceptors. Subsequently, the influence of a 10 nm gold coating without and with
      an Alq3 spacer layer was studied and the experimental results were analyzed with
      the multilevel model. Without a spacer layer, a significant PL quenching and
      lifetime reduction of the near band-edge emission is found. The behavior is
      attributed to surface band-bending and Forster energy transfer from excitons to
      surface plasmons in the gold layer. Inserting a 5 nm Alq3 spacer layer reduces
      the PL quenching and lifetime reduction which is consistent with a reduced band
      bending and Forster energy transfer. Increasing the spacer layer to 30 nm results
      in lifetimes which are similar to uncoated structures, showing a significantly
      decreased influence of the gold coating on the excitonic dynamics.

PMID- 29064369
TI  - Allosteric fine-tuning of the conformational equilibrium poises the chaperone BiP
      for post-translational regulation.
AB  - BiP is the only Hsp70 chaperone in the endoplasmic reticulum (ER) and similar to
      other Hsp70s, its activity relies on nucleotide- and substrate-controllable
      docking and undocking of its nucleotide-binding domain (NBD) and substrate
      binding domain (SBD). However, little is known of specific features of the BiP
      conformational landscape that tune BiP to its unique tasks and the ER
      environment. We present methyl NMR analysis of the BiP chaperone cycle that
      reveals surprising conformational heterogeneity of ATP-bound BiP that
      distinguishes BiP from its bacterial homologue DnaK. This unusual poise enables
      gradual post-translational regulation of the BiP chaperone cycle and its
      chaperone activity by subtle local perturbations at SBD allosteric 'hotspots'. In
      particular, BiP inactivation by AMPylation of its SBD does not disturb Hsp70
      inter-domain allostery and preserves BiP structure. Instead it relies on a
      redistribution of the BiP conformational ensemble and stabilization the domain
      docked conformation in presence of ADP and ATP.

PMID- 29064372
TI  - Cellulose nanocrystal-derived hollow mesoporous carbon spheres and their
      application as a metal-free catalyst.
AB  - In this contribution, we demonstrate the fabrication of hollow mesoporous carbon
      spheres (HCSs) derived from cellulose nanocrystals (CNCs). The HCSs were prepared
      by templating CNCs onto sacrificial silica spheres followed by heat treatment.
      Mesoporous carbon spheres result from the removal of the silica spheres by
      etching. The walls of the HCSs are approximately 4 nm thick and are composed of
      amorphous and graphitic carbon. The catalytic activity of the HCSs was
      investigated for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) by
      sodium borohydride (NaBH4). The present investigation reveals the outstanding
      catalytic activity of these particles. The reaction rate followed pseudo-first
      order kinetics with k value of 4.72 * 10-3 s-1 and activity parameter of 52.2 s-1
      g-1, which showed superior performance compared to that of metal nanoparticle and
      metal nanoparticle-carbon hybrid based catalysts.

PMID- 29064373
TI  - The influence of the topography and physico-chemical properties of the cuticle
      surface on the wettability and adhesive properties of the elytra of the dung
      beetle Geotrupes stercorarius (Coleoptera, Scarabaeidae).
AB  - The elytral surface of dung beetles is generally accepted to be self-cleaning due
      to its anti-adhesive properties. In this article, the wettability and adhesive
      properties of elytral surface (intact and treated with Acetone and Ethanol) of
      the beetle Geotrupes stercorarius were characterized. Since these properties are
      influenced by the surface structure and chemistry, the micro- and nanostructure
      of the elytra were observed using scanning electron microscopy and the surface
      roughness were estimated with white light interferometery, whereas the water
      contact angle and adhesion force of the elytra were evaluated using contact angle
      measurement device and force transducer, respectively. The results show that the
      microstructure of the elytra changed greatly after different chemical treatments
      and the changes in wettability were mainly related to the changes of elytra
      roughness after treatments. The differences in adhesion force between differently
      treated elytra and wet sand indicate that the molecular polarity of the elytral
      surface is decisive for its anti-adhesive (self-cleaning) property.

PMID- 29064374
TI  - In vitro toxic effects of reduced graphene oxide nanosheets on lung cancer cells.
AB  - The intriguing properties of reduced graphene oxide (rGO) have paved the way for
      a number of potential biomedical applications such as drug delivery, tissue
      engineering, gene delivery and bio-sensing. Over the last decade, there have been
      escalating concerns regarding the possible toxic effects, behaviour and fate of
      rGO in living systems and environments. This paper reports on integrative
      chemical-biological interactions of rGO with lung cancer cells, i.e. A549 and
      SKMES-1, to determine its potential toxicological impacts on them, as a function
      of its concentration. Cell viability, early and late apoptosis and necrosis were
      measured to determine oxidative stress potential, and induction of apoptosis for
      the first time by comparing two lung cancer cells. We also showed the general
      trend between cell death rates and concentrations for different cell types using
      a Gaussian process regression model. At low concentrations, rGO was shown to
      significantly produce late apoptosis and necrosis rather than early apoptotic
      events, suggesting that it was able to disintegrate the cellular membranes in a
      dose dependent manner. For the toxicity exposures undertaken, late apoptosis and
      necrosis occurred, which was most likely resultant from limited bioavailability
      of unmodified rGO in lung cancer cells.

PMID- 29064375
TI  - On algorithms for calculating arterial pulse pressure variation during major
      surgery.
AB  - OBJECTIVE: Arterial pulse pressure variation (PPV) is widely used for predicting
      fluid responsiveness and supporting fluid management in the operating room and
      intensive care unit. Available PPV algorithms have been typically validated for
      fluid responsiveness during episodes of hemodynamic stability. Yet, little is
      known about the performance of PPV algorithms during surgery, where fast changes
      of the blood pressure may affect the robustness of the presented PPV value. This
      work provides a comprehensive understanding of how various existing algorithmic
      designs affect the robustness of the presented PPV value during surgery, and
      proposes additional processing for the pulse pressure signal before calculating
      PPV. APPROACH: We recorded arterial blood pressure waveforms from 23 patients
      undergoing major abdominal surgery. To evaluate the performance, we designed
      three clinically relevant metrics. Main results and Significance: The results
      show that all algorithms performed well during episodes of hemodynamic stability.
      Moreover, it is demonstrated that the proposed processing helps improve the
      robustness of PPV during the entire course of surgery.

PMID- 29064376
TI  - Lifetime attributable risk as an alternative to effective dose to describe the
      risk of cancer for patients in diagnostic and therapeutic nuclear medicine.
AB  - The aim of this study is to implement lifetime attributable risk (LAR)
      predictions of cancer for patients of various age and gender, undergoing
      diagnostic investigations or treatments in nuclear medicine and to compare the
      outcome with a population risk estimate using effective dose and the
      International Commission on Radiological Protection risk coefficients. The
      radiation induced risk of cancer occurrence (incidence) or death from four
      nuclear medicine procedures are estimated for both male and female between 0 and
      120 years. Estimations of cancer risk are performed using recommended
      administered activities for two diagnostic (18F-FDG and 99mTc-phosphonate
      complex) and two therapeutic (131I-iodide and 223Ra-dichloride)
      radiopharmaceuticals to illustrate the use of cancer risk estimations in nuclear
      medicine. For 18F-FDG, the cancer incidence for a male of 5, 25, 50 and 75 years
      at exposure is 0.0021, 0.0010, 0.0008 and 0.0003, respectively. For 99mTc
      phosphonates complex the corresponding values are 0.000 59, 0.000 34, 0.000 27
      and 0.000 13, respectively. For an 131I-iodide treatment with 3.7 GBq and 1%
      uptake 24 h after administration, the cancer incidence for a male of 25, 50 and
      75 years at exposure is 0.041, 0.029 and 0.012, respectively. For 223Ra
      dichloride with an administration of 21.9 MBq the cancer incidence for a male of
      25, 50 and 75 years is 0.31, 0.21 and 0.09, respectively. The LAR estimations are
      more suitable in health care situations involving individual patients or specific
      groups of patients than the health detriment based on effective dose, which
      represents a population average. The detriment consideration in effective dose
      adjusts the cancer incidence for suffering of non-lethal cancers while LAR
      predicts morbidity (incidence) or mortality (cancer). The advantages of these
      LARs are that they are gender and age specific, allowing risk estimations for
      specific patients or subgroups thus better representing individuals in health
      care than effective dose.

PMID- 29064377
TI  - 3D printing nano conductive multi-walled carbon nanotube scaffolds for nerve
      regeneration.
AB  - OBJECTIVE: Nanomaterials, such as carbon nanotubes (CNTs), have been introduced
      to modify the surface properties of scaffolds, thus enhancing the interaction
      between the neural cells and biomaterials. In addition to superior electrical
      conductivity, CNTs can provide nanoscale structures similar to those present in
      the natural neural environment. The primary objective of this study is to
      investigate the proliferative capability and differential potential of neural
      stem cells (NSCs) seeded on a CNT incorporated scaffold. APPROACH: Amine
      functionalized multi-walled carbon nanotubes (MWCNTs) were incorporated with a
      PEGDA polymer to provide enhanced electrical properties as well as nanofeatures
      on the surface of the scaffold. A stereolithography 3D printer was employed to
      fabricate a well-dispersed MWCNT-hydrogel composite neural scaffold with a
      tunable porous structure. 3D printing allows easy fabrication of complex 3D
      scaffolds with extremely intricate microarchitectures and controlled porosity.
      MAIN RESULTS: Our results showed that MWCNT-incorporated scaffolds promoted
      neural stem cell proliferation and early neuronal differentiation when compared
      to those scaffolds without the MWCNTs. Furthermore, biphasic pulse stimulation
      with 500 uA current promoted neuronal maturity quantified through protein
      expression analysis by quantitative polymerase chain reaction. SIGNIFICANCE:
      Results of this study demonstrated that an electroconductive MWCNT scaffold,
      coupled with electrical stimulation, may have a synergistic effect on promoting
      neurite outgrowth for therapeutic application in nerve regeneration.

PMID- 29064379
TI  - Resuscitation Training for Schoolchildren Worldwide: Kids Save Lives: Erratum.

PMID- 29064378
TI  - Technical characterization of five x-ray detectors for paediatric radiography
      applications.
AB  - Physical image quality of five x-ray detectors used in the paediatric imaging
      department is characterized with the aim of establishing the range/scope of
      imaging performance provided by these detectors for neonatal imaging. Two
      computed radiography (CR) detectors (MD4.0 powder imaging plate (PIP) and HD5.0
      needle imaging plate (NIP), Agfa HealthCare NV, B-2640 Mortsel, Belgium) and
      three flat panel detectors (FPD) (the Agfa DX-D35C and DX-D45C and the DRX-2530C
      (Carestream Health Inc., Rochester, NY 14608, USA)) were assessed. Physical image
      quality was characterized using the detector metrics given by the International
      Electrotechnical Commission (IEC 62220-1) to measure modulation transfer function
      (MTF), the noise power spectrum (NPS) and the detective quantum efficiency (DQE)
      using the IEC-specified beam qualities of RQA3 and RQA5. The DQE was evaluated at
      the normal operating detector air kerma (DAK) level, defined at 2.5 uGy for all
      detectors, and at factors of 1/3.2 and 3.2 times the normal level. MTF curves for
      the different detectors were similar at both RQA3 and RQA5 energies; the average
      spatial frequency for the 50% point (MTF0.5) at RQA3 was 1.26 mm-1, with a range
      from 1.20 mm-1 to 1.37 mm-1. The DQE of the NIP CR compared to the PIP CR was
      notably greater and similar to that for the FPD devices. At RQA3, average DQE for
      the FPD and NIP (at 0.5 mm-1; 2.5 uGy) was 0.57 compared to 0.26 for the PIP CR.
      At the RQA5 energy, the DRX-2530C and the DX-D45C had the highest DQE (~0.6 at
      0.5 mm-1; 2.5 uGy). Noise separation analysis using the polynomial model showed
      higher electronic noise for the DX-D35C and DRX-2530C detectors; this explains
      the reduced DQE seen at 0.7 uGy/image. The NIP CR detector offers notably
      improved DQE performance compared to the PIP CR system and a value similar to the
      DQE for FPD devices at the RQA3 energy.

PMID- 29064381
TI  - A Novel Way to Secure the Laryngeal Mask Airway During Oral Surgery Procedures:
      Erratum.

PMID- 29064382
TI  - Age-Related Thermoregulatory Differences in a Warm Operating Room Environment
      (Approximately 26 degrees C): Erratum.

PMID- 29064383
TI  - Recent Advances in the Isolation, Synthesis and Biological Activity of Marine
      Guanidine Alkaloids.
AB  - Marine organisms are prolific resources of guanidine-containing natural products
      with intriguing structures and promising biological activities. These molecules
      have therefore attracted the attention of chemists and biologists for their
      further studies towards potential drug leads. This review focused on the
      guanidine alkaloids derived from marine sources and discussed the recent progress
      on their isolation, synthesis and biological activities, covering the literature
      from the year 2010 to the present.

PMID- 29064384
TI  - Association between Obesity and Puberty Timing: A Systematic Review and Meta
      Analysis.
AB  - This systematic review and meta-analysis examined the associations between
      obesity and puberty timing based on scientific evidence. Eight electronic
      databases were searched up to February 2017 for eligible studies, and two
      reviewers screened the articles and extracted the data independently. A total of
      11 cohort studies with 4841 subjects met the inclusion criteria. Compared with
      the group of normal-weight girls, the obese group had more girls with menarche
      (RR: 1.87, 95% CI: 1.59-2.19, 2 studies). The number of girls with early puberty
      was significantly higher in the obese group than the normal weight group (RR:
      2.44, 95% CI: 1.32-4.52, 5 studies). However, no differences were detected
      between girls who were obese or normal weight at age of menarche (WMD: -0.53
      years, 95% CI: -1.24-0.19, 2 studies). There is no consistent result in the
      relationship between obesity and timing of pubertal onset in boys. Obesity may
      contribute to early onset of puberty in girls, while in boys, there is
      insufficient data. Given the limited number of cohort studies included in this
      meta-analysis, high-quality studies with strong markers of puberty onset, as well
      as standardized criteria for defining obesity are needed.

PMID- 29064385
TI  - Three-Axis Ground Reaction Force Distribution during Straight Walking.
AB  - We measured the three-axis ground reaction force (GRF) distribution during
      straight walking. Small three-axis force sensors composed of rubber and sensor
      chips were fabricated and calibrated. After sensor calibration, 16 force sensors
      were attached to the left shoe. The three-axis force distribution during straight
      walking was measured, and the local features of the three-axis force under the
      sole of the shoe were analyzed. The heel area played a role in receiving the
      braking force, the base area of the fourth and fifth toes applied little vertical
      or shear force, the base area of the second and third toes generated a portion of
      the propulsive force and received a large vertical force, and the base area of
      the big toe helped move the body's center of mass to the other foot. The results
      demonstrate that measuring the three-axis GRF distribution is useful for a
      detailed analysis of bipedal locomotion.

PMID- 29064386
TI  - The Role of PXR Genotype and Transporter Expression in the Placental Transport of
      Lopinavir in Mice.
AB  - Lopinavir (LPV), an antiretroviral protease inhibitor frequently prescribed in
      HIV-positive pregnancies, is a substrate of Abcb1 and Abcc2. As differences in
      placental expression of these transporters were seen in Pregnane X Receptor (PXR)
      -/- mice, we examined the impact of placental transporter expression and fetal
      PXR genotype on the fetal accumulation of LPV. PXR +/- dams bearing PXR +/+, PXR
      +/-, and PXR -/- fetuses were generated by mating PXR +/- female mice with PXR +/
      males. On gestational day 17, dams were administered 10 mg/kg LPV (i.v.) and
      sacrificed 30 min post injection. Concentrations of LPV in maternal plasma and
      fetal tissue were measured by LC-MS/MS, and transporter expression was determined
      by quantitative RT-PCR. As compared to the PXR +/+ fetal units, placental
      expression of Abcb1a, Abcc2, and Abcg2 mRNA were two- to three-fold higher in PXR
      -/- fetuses (p < 0.05). Two-fold higher fetal:maternal LPV concentration ratios
      were also seen in the PXR +/+ as compared to the PXR -/- fetuses (p < 0.05), and
      this significantly correlated to the placental expression of Abcb1a (r = 0.495; p
      < 0.005). Individual differences in the expression of placental transporters due
      to genetic or environmental factors can impact fetal exposure to their
      substrates.

PMID- 29064387
TI  - Fiber-Optic Point-Based Sensor Using Specklegram Measurement.
AB  - Here, we report a fiber-optic point-based sensor to measure temperature and
      weight based on correlated specklegrams induced by spatial multimode
      interference. The device is realized simply by splicing a multimode fiber (MMF)
      to a single-mode fiber (SMF) with a core offset. A series of experiments
      demonstrates the approximately linear relation between the correlation
      coefficient and variation. Furthermore, we show the potential applications of the
      refractive index sensing of our device by disconnecting the splicing point of MMF
      and SMF. A modification of the algorithm in order to improve the sensitivity of
      the sensor is also discussed at the end of the paper.

PMID- 29064388
TI  - The Role of Platelet-Derived ADP and ATP in Promoting Pancreatic Cancer Cell
      Survival and Gemcitabine Resistance.
AB  - Platelets have been demonstrated to be vital in cancer epithelial-mesenchymal
      transition (EMT), an important step in metastasis. Markers of EMT are associated
      with chemotherapy resistance. However, the association between the development of
      chemoresistance, EMT, and the contribution of platelets to the process, is still
      unclear. Here we report that platelets regulate the expression of (1) human
      equilibrative nucleoside transporter 1 (hENT1) and (2) cytidine deaminase (CDD),
      markers of gemcitabine resistance in pancreatic cancer. Human ENT1 (hENT1) is
      known to enable cellular uptake of gemcitabine while CDD deactivates gemcitabine.
      Knockdown experiments demonstrate that Slug, a mesenchymal transcriptional factor
      known to be upregulated during EMT, regulates the expression of hENT1 and CDD.
      Furthermore, we demonstrate that platelet-derived ADP and ATP regulate Slug and
      CDD expression in pancreatic cancer cells. Finally, we demonstrate that
      pancreatic cancer cells express the purinergic receptor P2Y12, an ADP receptor
      found mainly on platelets. Thus ticagrelor, a P2Y12 inhibitor, was used to
      examine the potential therapeutic effect of an ADP receptor antagonist on cancer
      cells. Our data indicate that ticagrelor negated the survival signals initiated
      in cancer cells by platelet-derived ADP and ATP. In conclusion, our results
      demonstrate a novel role of platelets in modulating chemoresistance in pancreatic
      cancer. Moreover, we propose ADP/ATP receptors as additional potential drug
      targets for treatment of pancreatic cancer.

PMID- 29064389
TI  - Identification of Gene Expression Changes in the Aorta of ApoE Null Mice Fed a
      High-Fat Diet.
AB  - Atherosclerosis is a chronic multifactorial inflammatory disease with high
      worldwide prevalence, and has become the leading cause of death. In the present
      study, we analyzed global gene expression changes in the aorta of Apolipoprotein
      E (ApoE) null mice fed a high-fat diet by using RNA-seq. We identified a total of
      280 differentially expressed genes, of which 163 genes were upregulated and 117
      genes were downregulated by high-fat diet compared with normal diet. Functional
      clustering and gene network analysis revealed that fatty acid metabolic process
      is crucial for atherosclerosis. By examining of the promoter regions of
      differentially expressed genes, we identified four causal transcription factors.
      Additionally, through connectivity map (CMap) analysis, multiple compounds were
      identified to have anti-atherosclerotic effects due to their ability to reverse
      gene expression during atherosclerosis. Our study provides a valuable resource
      for in-depth understanding of the mechanism underlying atherosclerosis.

PMID- 29064390
TI  - Asymmetrical Competition between Aedes aegypti and Culex quinquefasciatus
      (Diptera: Culicidae) Coexisting in Breeding Sites.
AB  - Aedes aegypti and Culex quinquefasciatus are mosquito vectors for several
      tropical diseases that represent a current public health problem. The ecological
      requirements for each species are different, however, both species show high
      biological adaptability, which promotes their coexistence in the same breeding
      sites. The purpose of this study was to assess the effect of larval association
      between Ae. aegypti and Cx. quinquefasciatus under different laboratory
      conditions of food supply and temperature, and under field simulated conditions
      like peridomestic containers. Our findings showed that under field simulated
      conditions there was no asymmetrical competition in mixed cultures with the
      different Cx. quinquefasciatus/Ae. aegypti ratios tested. However, under
      laboratory conditions in which different doses of food supply were evaluated, it
      was observed that competition between the two species takes place. Larval
      coexistence under food scarcity conditions (0.95 mg/larva) showed that Ae.
      aegypti had a greater adult emergence than Cx. quinquefasciatus and was capable
      of depriving Cx. quinquefasciatus of the food needed to complete metamorphosis.
      In an intermediate dose of food (1.9 mg/larva), the dry weight of Cx.
      quinquefasciatus adults decreased, and their larval development time increased
      when Cx. quinquefasciatus/Ae. aegypti ratio was low. Also, a temperature effect
      was assessed demonstrating that Cx. quinquefasciatus was more vulnerable to
      changes in temperature. We suggest that Ae. aegypti is more successful in
      exploiting microhabitats when food is scarce, due to its scrape active feeding
      habitats and fast larval development times. Therefore, in conditions of food
      paucity both species will compete, and Ae. aegypti larvae will prevail.

PMID- 29064391
TI  - Transcriptomic Analysis of Gibberellin- and Paclobutrazol-Treated Rice Seedlings
      under Submergence.
AB  - Submergence stress is a limiting factor for rice growing in rainfed lowland areas
      of the world. It is known that the phytohormone gibberellin (GA) has negative
      effects on submergence tolerance in rice, while its inhibitor paclobutrazol (PB)
      does the opposite. However, the physiological and molecular basis underlying the
      GA- and PB-regulated submergence response remains largely unknown. In this study,
      we reveal that PB could significantly enhance rice seedling survival by retaining
      a higher level of chlorophyll content and alcohol dehydrogenase activity, and
      decelerating the consumption of non-structure carbohydrate when compared with the
      control and GA-treated samples. Further transcriptomic analysis identified 3936
      differentially expressed genes (DEGs) among the GA- and PB-treated samples and
      control, which are extensively involved in the submergence and other abiotic
      stress responses, phytohormone biosynthesis and signaling, photosynthesis, and
      nutrient metabolism. The results suggested that PB enhances rice survival under
      submergence through maintaining the photosynthesis capacity and reducing nutrient
      metabolism. Taken together, the current study provided new insight into the
      mechanism of phytohormone-regulated submergence response in rice.

PMID- 29064392
TI  - Relationship between Bone Health Biomarkers and Cardiovascular Risk in a General
      Adult Population.
AB  - : Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge
      as closely related conditions, showing common risk factors and/or
      pathophysiological mechanisms. The aim of this study was to evaluate the
      association between bone health markers (BHM) and individual CV risk factors and
      overall CV risk (FRAMINGHAM-FRS, and PROCAM scores) in a general adult
      population. METHODS: In 103 subjects (21 males; age: 56 +/- 12 years), vitamin D
      (25(OH)D), osteocalcin (OC), bone alkaline phospatase (BALP), procollagen I
      aminoterminal propeptide (P1NP), CTx-telopeptide, as well clinical history and
      life style were evaluated. RESULTS: Aging (p < 0.001) and glycemia (p < 0.05)
      emerged as independent 25(OH)D predictors. Aging (p < 0.001), male sex (p <
      0.05), and obesity (p < 0.05) represented independent OC determinants. Aging (p <
      0.05) was the only independent BALP determinant. After multivariate adjustment,
      low 25(OH)D (<20 ng/mL) (Odds ratio OR (95% confidence intervals CI)) (5 (1.4-18)
      p < 0.05) and elevated OC (>75th percentile-16.6 ng/mL) (6.7 (1.9-23.8) p < 0.01)
      were found to be significant FRS predictors, while subjects with elevated OC
      and/or BALP (>75th percentile-9.8 MUg/L) showed a higher CV risk as estimated by
      PROCAM (3.6 (1.2-10.7) p < 0.05). CTx and P1NP did not significantly correlate
      with CV risk factors or scores. CONCLUSION: As we go further into bone and CV
      physiology, it is evident that a close relationship exists between these
      diseases. Further studies are needed to investigate mechanisms by which bone
      turnover markers are related to metabolic risk and could modulate CV risk. This
      knowledge may help to develop possible multiple-purpose strategies for both CV
      disease and OP prevention and treatment.

PMID- 29064394
TI  - Is Obesity More Than a Double Burden among People with Mobility Disability? The
      Effect of Obesity on HRQoL and Participation in Society.
AB  - Obesity is more common in individuals with mobility disability than in those
      without this condition. Individuals with mobility disability also have lower
      health-related quality of life (HRQoL) and are limited in their participation in
      society. Therefore, this study aimed to investigate the body mass index (BMI)
      status and the association of overweight or obesity on HRQoL and participation in
      society among those with mobility disability in comparison to those without
      mobility disability. This cross-sectional study was based on a health survey
      conducted in Sweden in 2012 (n = 18,322; age, 18-64 years). Logistic regression
      with and without interaction analysis was applied. Effect modification by
      overweight status was significant for, moderate pain. For obesity, effect
      modification was seen for low general health, pain (moderate and severe), and not
      participating in work. BMI was higher among those with mobility disability, but
      no associations between overweight or obesity and HRQoL or participation in
      society were observed for those with mobility disability. Overweight and obesity
      did not add an additional burden to mobility disability, probably because
      mobility disability is associated with low HRQoL and low participation in
      society. Despite these results, population obesity prevention strategies are
      still needed.

PMID- 29064393
TI  - Genome-Wide Identification and Structural Analysis of bZIP Transcription Factor
      Genes in Brassica napus.
AB  - The basic region/leucine zipper motif (bZIP) transcription factor family is one
      of the largest families of transcriptional regulators in plants. bZIP genes have
      been systematically characterized in some plants, but not in rapeseed (Brassica
      napus). In this study, we identified 247 BnbZIP genes in the rapeseed genome,
      which we classified into 10 subfamilies based on phylogenetic analysis of their
      deduced protein sequences. The BnbZIP genes were grouped into functional clades
      with Arabidopsis genes with similar putative functions, indicating functional
      conservation. Genome mapping analysis revealed that the BnbZIPs are distributed
      unevenly across all 19 chromosomes, and that some of these genes arose through
      whole-genome duplication and dispersed duplication events. All expression
      profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from
      17 different B. napus ZS11 tissues with 42 various developmental stages. These
      genes exhibited different expression patterns in various tissues, revealing that
      these genes are differentially regulated. Our results provide a valuable
      foundation for functional dissection of the different BnbZIP homologs in B. napus
      and its parental lines and for molecular breeding studies of bZIP genes in B.
      napus.

PMID- 29064395
TI  - Growth, Toxin Production and Allelopathic Effects of Pseudo-nitzschia multiseries
      under Iron-Enriched Conditions.
AB  - In order to assess the effects of Fe-enrichment on the growth and domoic acid
      (DA) production of the toxigenic diatom Pseudo-nitzschia multiseries, static
      cultures that received the addition of different iron (Fe) concentrations were
      maintained for 30 days. Intra- and extracellular DA concentrations were evaluated
      over time, and growth and chain-formation were compared to those of non-toxic
      diatoms, Bacillaria sp. Growth rates of P. multiseries (MU = 0.45-0.73 d-1) were
      similar among cultures containing different Fe concentrations. Likewise, the
      similar incidence and length of P. multiseries stepped cell chains (usually 2-4;
      up to 8-cell long) among the treatments reinforces that the cultures were not
      growth-inhibited under any condition tested, suggesting an efficient Fe
      acquisition mechanism. Moreover, DA concentrations were significantly higher
      under the highest Fe concentration, indicating that Fe is required for toxin
      synthesis. Bacillaria sp. reached comparable growth rates under the same Fe
      concentrations, except when the dissolved cell contents from a P. multiseries
      culture was added. The 50-70% reduction in cell density and 70-90% decrease in
      total chlorophyll-a content of Bacillaria sp. at early stationary growth phase
      indicates, for the first time, an allelopathic effect of undetermined compounds
      released by Pseudo-nitzschia to another diatom species.

PMID- 29064396
TI  - Intermittent Administration of Parathyroid Hormone 1-34 Enhances Osteogenesis of
      Human Mesenchymal Stem Cells by Regulating Protein Kinase Cdelta.
AB  - Human mesenchymal stem cells (hMSCs) can differentiate into osteoblasts and are
      regulated by chemical cues. The recombinant N-terminal (1-34 amino acids)
      fragment of the parathyroid hormone (PTH (1-34)) is identified to promote
      osteogenesis. The osteoanabolic effects of intermittent PTH (1-34) treatment are
      linked to a complex consisting of signaling pathways; additionally, protein
      kinase C (PKC) act as mediators of multifunctional signaling transduction
      pathways, but the role of PKC delta (PKCdelta), a downstream target in regulating
      osteoblast differentiation during intermittent administration of PTH (1-34) is
      less studied and still remains elusive. The purpose of this study is to examine
      the role of PKCdelta during intermittent and continuous PTH (1-34) administration
      using osteoblast-lineage-committed hMSCs. Relative gene expression of osteoblast
      specific genes demonstrated significant upregulation of RUNX2, type I Collagen,
      ALP, and Osterix and increased alkaline phosphatase activity in the presence of
      PTH (1-34). Intermittent PTH (1-34) administration increased PKC activity at day
      7 of osteogenic differentiation, whereas inhibition of PKC activity attenuated
      these effects. In addition, the specific isoform PKCdelta was activated upon
      treatment. These findings demonstrate that intermittent PTH (1-34) treatment
      enhances the osteogenesis of hMSCs by upregulating osteoblast-specific genes via
      PKCdelta activation.

PMID- 29064397
TI  - Association of Vitamin D3 Level with Breast Cancer Risk and Prognosis in African
      American and Hispanic Women.
AB  - Background: This study investigated the association of vitamin D3 levels with
      breast cancer risk and progression in African-Americans and Hispanics. Methods: A
      total of 237 African-American (Cases = 119, Control = 118) and 423 Hispanic women
      (Cases = 124, Control = 299) were recruited in the study. Blood samples were
      collected at the time of breast cancer screening and prior to cancer treatment
      for 4 weeks on average for the cases. The serum 25-hydroxyvitamin D (25(OH)D3)
      was measured at a Quest-Diagnostics facility. Results: The results showed that
      69.2% of African-Americans and 37.8% of Hispanics had 25(OH)D3 levels below 20
      ng/mL. The 25(OH)D3 level below 20 ng/mL was significantly associated with breast
      cancer in both African-Americans (OR = 2.5, 95% CI = 1.3-4.8) and Hispanics (OR =
      1.9, 95% CI = 1.1-3.0). However, the predicted probabilities of breast cancer in
      African-Americans were significantly higher than in Hispanics (p < 0.001). The
      25(OH)D3 below 20 ng/mL was significantly associated with triple negative breast
      cancer (TNBC) in African-Americans (OR = 5.4, p = 0.02, 95% CI = 1.4-15), but not
      in Hispanics in our cohort of participants. Levels of 25(OH)D3 below 26 ng/mL
      predicts a decrease in disease-free survival, but it was not an independent
      predictor. Conclusions: Our data shows an association between 25(OH)D3 levels and
      the risk of breast cancer. Further studies on the relationship between 25(OH)D3
      level and breast cancer risk are warranted.

PMID- 29064398
TI  - Coumestrol Epigenetically Suppresses Cancer Cell Proliferation: Coumestrol Is a
      Natural Haspin Kinase Inhibitor.
AB  - Targeting epigenetic changes in gene expression in cancer cells may offer new
      strategies for the development of selective cancer therapies. In the present
      study, we investigated coumestrol, a natural compound exhibiting broad anti
      cancer effects against skin melanoma, lung cancer and colon cancer cell growth.
      Haspin kinase was identified as a direct target protein of coumestrol using
      kinase profiling analysis. Histone H3 is a direct substrate of haspin kinase. We
      observed haspin kinase overexpression as well as greater phosphorylation of
      histone H3 at threonine 3 (Thr-3) in the cancer cells compared to normal cells.
      Computer modeling using the Schrodinger Suite program identified the binding
      interface within the ATP binding site. These findings suggest that the anti
      cancer effect of coumestrol is due to the direct targeting of haspin kinase.
      Coumestrol has considerable potential for further development as a novel anti
      cancer agent.

PMID- 29064400
TI  - Industrial-Graded Epoxy Nanocomposites with Mechanically Dispersed Multi-Walled
      Carbon Nanotubes: Static and Damping Properties.
AB  - The majority of currently published dispersion protocols of carbon nanotubes rely
      on techniques that are not scalable to an industrial level. This work shows how
      to obtain polymer nanocomposites with good mechanical characteristics using multi
      walled carbon nanotubes epoxy resins obtained by mechanical mixing only. The
      mechanical dispersion method illustrated in this work is easily scalable to
      industrial level. The high shearing force due to the complex field of motion
      produces a good and reproducible carbon nanotube dispersion. We have tested an
      industrial epoxy matrix with good baseline mechanical characteristics at
      different carbon nanotube weight loads. ASTM-derived tensile and compressive
      tests show an increment in both Young's modulus and compressive strength compared
      with the pristine resin from a starting low wt %. Comparative vibration tests
      show improvement in the damping capacity. The new carbon nanotube enhanced epoxy
      resin has superior mechanical proprieties compared to the market average
      competitor, and is among the top products in the bi-components epoxy resins
      market. The new dispersion method shows significant potential for the industrial
      use of CNTs in epoxy matrices.

PMID- 29064399
TI  - Pharmabiotics as an Emerging Medication for Metabolic Syndrome and Its Related
      Diseases.
AB  - Metabolic syndrome (MetS) is a cluster of metabolic risk factors associated with
      central obesity, hyperglycemia, insulin resistance, dyslipidemia and high blood
      pressure. In recent decades, because of the remarkable increase in both
      prevalence and severity, MetS and its related diseases such as cardiovascular
      diseases (CVDs), obesity, hypertension and diabetes have become the main global
      burden and challenge in strategic management involving prevention and treatment.
      However, currently, the preventions and treatments based on pharmaceutical
      interventions do not provide a solution for MetS and its related diseases.
      Recently, gut microbiota showed clear evidence of preventing and/or treating
      MetS, shedding light on treating MetS and its related diseases through a
      completely different approach. In this review, we will interpret the effects of
      current pharmaceutical drugs used in preventing and treating MetS and its related
      diseases to understand remaining issues of those interventions. We will explore
      the possibility of developing gut microbiota as pharmabiotics in a completely new
      medication option for treating MetS and its related diseases.

PMID- 29064401
TI  - Impact of Psychosocial Environment on Young Children's Emotional and Behavioral
      Difficulties.
AB  - Objective: The impact of maternal psychosocial stress on young children's mental
      difficulties is unclear. This study investigated the joint effects of the
      socioeconomic status and parent-child relationships on emotional and behavioral
      difficulties in preschool children. Methods: The case-control study included 1416
      mothers and their 4-6 year-old children pairs, living in Kaunas city, Lithuania.
      The parent-child relationships were measured using the Parent-Child Dysfunctional
      Interaction subscale. Children's mental health difficulties were assessed by the
      Strengths and Difficulties Questionnaire. We used logistic regression models to
      indicate the strength of the associations. Results: Lower socioeconomic status
      women more often than higher ones reported pathological mother-child relations.
      Low education level was associated with statistically significant increase
      adjusted odds ratios for emotional symptoms and total behavioral difficulties.
      With reference to the group of better-educated mothers and normal mother-child
      relations, low education and pathological mother-child relations statistically
      significantly increased the risk of total difficulties in 4-6 year-old children;
      the adjusted odds ratios were 2.45; 95% CI 1.51-3.99. Conclusions: Pathological
      mother-child relations strengthened the effect of lower education on the
      increased risk of emotional and behavioral difficulties in preschool-age
      children. Measures oriented towards health behavior and psychosocial difficulties
      management may decrease children's emotional and behavioral difficulties.

PMID- 29064402
TI  - Dermaseptin-PH: A Novel Peptide with Antimicrobial and Anticancer Activities from
      the Skin Secretion of the South American Orange-Legged Leaf Frog, Pithecopus
      (Phyllomedusa) hypochondrialis.
AB  - The dermaseptin peptides, mainly derived from the skin secretions of Hylidae
      frogs, belong to a superfamily of antimicrobial peptides and exhibit diverse
      antimicrobial and anticancer activities with low cytotoxicity. Here, we reported
      a novel dermaseptin peptide, from the South American orange-legged leaf frogs,
      Pithecopus (Phyllomedusa) hypochondrialis, processing the shortest peptide
      length, namely Dermaseptin-PH. The complementary DNA (cDNA) encoding biosynthetic
      precursor of Dermaseptin-PH was initially identified by the rapid amplification
      of cDNA ends PCR (RACE-PCR) technique from the skin secretion. The predicted
      primary structure was confirmed by a combination of reverse-phase high
      performance liquid chromatography (RP-HPLC) and MS/MS fragmentation from the skin
      secretion. Chemically-synthetic Dermaseptin-PH was investigated using a range of
      bioactivity assessment assays to evaluate the biological activities and
      cytotoxicity of Dermaseptin-PH. Dermaseptin-PH inhibited the growth of Gram
      negative bacteria, Gram-positive bacteria, and pathogenic yeast Candidaalbicans.
      In addition, Dermaseptin-PH showed a broad-spectrum of anticancer activities
      against several cancer cell lines including MCF-7, H157, U251MG, MDA-MB-435S, and
      PC-3. The potent antimicrobial and anticancer activities of Dermaseptin-PH make
      it a promising candidate in the discovery of new drugs for clinical applications,
      and the relatively short sequence of Dermaseptin-PH can provide new insight for
      the research and structural modification of new peptide drugs.

PMID- 29064404
TI  - Application of Sodium Selenite in the Prevention and Treatment of Cancers.
AB  - Selenium is an essential trace element that occurs in nature, in both inorganic
      and organic forms. This element participates in numerous biochemical processes,
      including antioxidant potential, but the mechanism of its anti-cancer action is
      still not well known. It should be noted that the anti-cancer properties of
      selenium depends on its chemical form, therapeutic doses, and the tumor type.
      Higher nutritional doses of selenium can stimulate human immune system. There are
      several hypotheses concerning the anticancer activity of selenium, including
      oxidation of sulfhydryl groups in proteins causing their conformational
      alterations. Conformational changes in proteins have the ability to weaken the
      activity of enzymes involved in the metabolism of cancer cells. In case of human
      fibrinogen sodium selenite, but not selenate, it inhibits protein disulfide
      exchange reactions, thus preventing formation of a hydrophobic polymer termed
      parafibrin, circulatory accumulation, of which is associated with numerous
      degenerative diseases. Parafibrin can specifically form a protein coat around
      tumor cells that is completely resistant to degradation induced with lymphocyte
      protease. In this way, cancer cells become protected against destruction by the
      organism's immune system. Other possible mechanisms of anticancer action of
      selenium are being still investigated.

PMID- 29064403
TI  - Characterization of Three Ocular Clinical Isolates of P. aeruginosa: Viability,
      Biofilm Formation, Adherence, Infectivity, and Effects of Glycyrrhizin.
AB  - We selectively characterized three isolates from Pseudomonas aeruginosa keratitis
      patients and how glycyrrhizin (GLY) affected them. Type III toxins were
      determined using polymerase chain reaction (PCR). Minimum Inhibitory
      Concentration (MIC) of GLY and assays for its effects on: time kill, bacterial
      permeability, and biofilm/adhesion were done. In vivo, C57BL/6 (B6) mice were
      treated topically with GLY after G81007 infection. Clinical score, photography
      with a slit lamp and RT-PCR were used to assess treatment effects. Isolates
      expressed exoS and exoT, but not exoU. MIC for all isolates was 40 mg/mL GLY and
      bacteriostatic effects were seen for G81007 after treatment using time kill
      assays. From viability testing, GLY treatment significantly increased the number
      of permeabilized bacteria (live/dead assay). Isolates 070490 and G81007 formed
      more biofilms compared with R59733 and PAO1 (control). GLY-treated bacteria had
      diminished biofilm compared with controls for all isolates. GLY reduced adherence
      of the G81007 isolate to cultured cells and affected specific biofilm associated
      systems tested by reverse transcription PCR (RT-PCR). In vivo, after G81007
      infection, GLY treatment reduced clinical score and messenger RNA (mRNA)
      expression of IL-1beta, TNF-alpha, CXCL2 and HMGB1. This study provides evidence
      that GLY is bacteriostatic for G81007. It also affects biofilm production,
      adherence to cultured cells, and an improved keratitis outcome.

PMID- 29064405
TI  - Influence of Afforestation on the Species Diversity of the Soil Seed Bank and
      Understory Vegetation in the Hill-Gullied Loess Plateau, China.
AB  - The Chinese Loess Plateau region has long been suffering from serious soil
      erosion. Thus, large-scale afforestation has continued during the past decades in
      order to control soil erosion. Afforestation can dramatically alter nutrient
      cycles, affect soil-carbon storage, and change hydrology. However, it is unknown
      how afforestation influences species diversity of the soil seed bank and
      understory vegetation compared with spontaneous restoration of abandoned land.
      Forest land with trees planted 30 years ago, abandoned slope land restored
      spontaneously for 30 years, and the corresponding slopes with remnant natural
      vegetation were selected as sampling sites. The species richness both in the soil
      seed bank and vegetation was significantly higher on the afforested slope
      compared to the spontaneously restored abandoned land. The species similarity
      between the afforested slope and the remnant slope land was high both in the soil
      seed bank and standing vegetation compared to the abandoned land. The soil seed
      bank density varied from 1778 +/- 187 to 3896 +/- 221 seeds/m2, and more than
      half of it was constituted by annual and biennial species, with no significant
      difference among sampling habitats. However, the afforested slope had higher seed
      density of grass and shrub/subshrubs compared to the abandoned slope. The present
      study indicates that in the study region, characterized by serious soil erosion,
      afforestation can better facilitate vegetation succession compared to
      spontaneously restoration of abandoned slope land.

PMID- 29064406
TI  - Diosgenin-Rich Yam Extract Enhances Cognitive Function: A Placebo-Controlled,
      Randomized, Double-Blind, Crossover Study of Healthy Adults.
AB  - Diosgenin, a yam-derived compound, was found to facilitate the repair of axonal
      atrophy and synaptic degeneration and improve memory dysfunction in a transgenic
      mouse model of Alzheimer's disease (AD). It was also found to enhance neuronal
      excitation and memory function even in normal mice. We hypothesized that
      diosgenin, either isolated or in an extract, may represent a new category of
      cognitive enhancers with essential activities that morphologically and
      functionally reinforce neuronal networks. This study aimed to investigate the
      effects of a diosgenin-rich yam extract on cognitive enhancement in healthy
      volunteers. For this placebo-controlled, randomized, double-blind, crossover
      study, 28 healthy volunteers (age: 20-81 years) were recruited from Toyama
      Prefecture, Japan, and was randomly assigned to receive either a yam extract or
      placebo. Preliminary functional animal experiments indicated that an oil solvent
      mediated the most efficient distribution of diosgenin into the blood and brain
      after oral administration, and was a critical factor in the cognitive benefits.
      Therefore, test samples (placebo and yam extract) were prepared with olive oil
      and formulated as soft capsules. The intake period was 12 weeks, and a 6-week
      washout period separated the two crossover intake periods. The Japanese version
      of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
      test was used for neurocognitive assessment, and the adverse effects were
      monitored through blood testing. Diosgenin-rich yam extract consumption for 12
      weeks yielded significant increases in total RBANS score. Among the 12 individual
      standard cognitive subtests, diosgenin-rich yam extract use significantly
      improved the semantic fluency. No adverse effects were reported. The diosgenin
      rich yam extract treatment appeared to safely enhance cognitive function in
      healthy adults.

PMID- 29064407
TI  - Flavonoid Naringenin Attenuates Oxidative Stress, Apoptosis and Improves
      Neurotrophic Effects in the Diabetic Rat Retina.
AB  - Diabetic retinopathy (DR) is one of the leading causes of decreased vision and
      blindness worldwide. Diabetes-induced oxidative stress is believed to be the key
      factor that initiates neuronal damage in the diabetic retina leading to DR.
      Experimental approaches to utilize dietary flavonoids, which possess both
      antidiabetic and antioxidant activities, might protect the retinal damage in
      diabetes. The aim of this study was to investigate the potential protective
      effects of naringenin in the retina of streptozotocin-induced diabetic rats.
      Diabetic rats were orally treated and untreated with naringenin (50 mg/kg/day)
      for five weeks and retinas were analyzed for markers of oxidative stress,
      apoptosis and neurotrophic factors. Systemic effects of naringenin treatments
      were also analyzed and compared with untreated groups. The results showed that
      elevated levels of thiobarbituric acid reactive substances (TBARs) and decreased
      level of glutathione (GSH) in diabetic rats were ameliorated with naringenin
      treatments. Moreover, decreased levels of neuroprotective factors (Brain derived
      neurotrophic factor (BDNF)), tropomyosin related kinase B (TrkB) and
      synaptophysin in diabetic retina were augmented with naringenin treatments. In
      addition, naringenin treatment ameliorated the levels of apoptosis regulatory
      proteins; B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax) and caspase
      3 in the diabetic retina. Thus, the study demonstrates the beneficial effects of
      naringenin that possesses anti-diabetic, antioxidant and antiapoptotic
      properties, which may limit neurodegeneration by providing neurotrophic support
      to prevent retinal damage in diabetic retinopathy.

PMID- 29064408
TI  - Avian Group D Rotaviruses: Structure, Epidemiology, Diagnosis, and Perspectives
      on Future Research Challenges.
AB  - In 1981, a new virus (virus 132) was described for the first time with
      morphological and biochemical similarities to rotaviruses (RVs), but without
      antigenic similarity to any of the previously known rotavirus groups.
      Subsequently, it was re-designated as D/132, and formed a new serogroup among
      rotaviruses, the group D rotavirus (RVD). Since their identification, RVs are the
      leading cause of enteritis and diarrhea in humans and various animal species, and
      are also associated with abridged growth, particularly in avian species.
      Recently, RVD has been suggested to play a role in the pathogenesis of runting
      and stunting syndrome (RSS), alongside other viruses such as reovirus,
      astrovirus, coronavirus, and others, all of which cause colossal economic losses
      to the poultry industry. RVD has been reported from several countries worldwide,
      and to date, only one complete genome sequence for RVD is available. Neither an
      immunodiagnostic nor a vaccine is available for the detection and prevention of
      RVD infection. Despite our growing understanding about this particular group,
      questions remain regarding its exact prevalence and pathogenecity, and the
      disease-associated annual losses for the poultry industry. Here, we describe the
      current knowledge about the identification, epidemiology, diagnosis, and
      prevention of RVD in poultry.

PMID- 29064409
TI  - Effect of Altering Dietary n-6:n-3 Polyunsaturated Fatty Acid Ratio with Plant
      and Marine-Based Supplement on Biomarkers of Bone Turnover in Healthy Adults.
AB  - Although there is accumulating evidence for a protective role of n-3
      polyunsaturated fatty acids (n-3 PUFAs) on bone health, there are limited studies
      that examine the effect of altering dietary n-6:n-3 PUFA ratio with plant and
      marine sources of n-3 PUFA on bone health. Healthy adults (n = 24) were
      randomized into an eight-week crossover study with a four-week washout between
      treatments, with each subject consuming three of four diets. The four diets
      differed in the dietary n-6:n-3 PUFA ratios and either had an algal oil
      supplement added or not: (Control diet (10:1); alpha-linolenic acid (ALA) diet
      (2:1); Eicosapentaenoic acid/Docosahexaenoic acid (EPA/DHA) diet (10:1 plus
      supplement (S) containing EPA/DHA; Combination diet (2:1 + S)). The supplement
      was microalgae oil that provided 1 g EPA + DHA/day. Flaxseed oil and walnuts
      provided 8.6 g of ALA/day in the 2:1 diets. Serum levels of c-telopeptide (CTX),
      procollagen Type I N-terminal peptide, and osteocalcin showed significant
      correlation with age but none of the bone markers or peroxisomal proliferator
      activated receptor-gamma mRNA expression was significantly different between the
      diets. Serum CTX was negatively associated with red blood cell membrane linoleic
      acid and ALA and positively associated with membrane DHA. Neither altering
      dietary n-6:n-3 PUFA ratio from a 10:1 to a 2:1 ratio nor adding EPA/DHA
      supplement significantly changed bone turnover in the short term in healthy
      adults.

PMID- 29064410
TI  - Lithium Ion Sensors.
AB  - The detection and monitoring of lithium in environmental and clinical settings is
      becoming increasingly important. In this review, sensors incorporating conductive
      polymers and lithium bronzes are discussed, together with electrochemical and
      spectroscopic approaches. Ionophore-based methods have been employed extensively,
      with varying degrees of selectivity and sensitivity, and these are discussed in
      depth.

PMID- 29064411
TI  - Comparison between Random Forests, Artificial Neural Networks and Gradient
      Boosted Machines Methods of On-Line Vis-NIR Spectroscopy Measurements of Soil
      Total Nitrogen and Total Carbon.
AB  - Accurate and detailed spatial soil information about within-field variability is
      essential for variable-rate applications of farm resources. Soil total nitrogen
      (TN) and total carbon (TC) are important fertility parameters that can be
      measured with on-line (mobile) visible and near infrared (vis-NIR) spectroscopy.
      This study compares the performance of local farm scale calibrations with those
      based on the spiking of selected local samples from both fields into an European
      dataset for TN and TC estimation using three modelling techniques, namely
      gradient boosted machines (GBM), artificial neural networks (ANNs) and random
      forests (RF). The on-line measurements were carried out using a mobile, fiber
      type, vis-NIR spectrophotometer (305-2200 nm) (AgroSpec from tec5, Germany),
      during which soil spectra were recorded in diffuse reflectance mode from two
      fields in the UK. After spectra pre-processing, the entire datasets were then
      divided into calibration (75%) and prediction (25%) sets, and calibration models
      for TN and TC were developed using GBM, ANN and RF with leave-one-out cross
      validation. Results of cross-validation showed that the effect of spiking of
      local samples collected from a field into an European dataset when combined with
      RF has resulted in the highest coefficients of determination (R2) values of 0.97
      and 0.98, the lowest root mean square error (RMSE) of 0.01% and 0.10%, and the
      highest residual prediction deviations (RPD) of 5.58 and 7.54, for TN and TC,
      respectively. Results for laboratory and on-line predictions generally followed
      the same trend as for cross-validation in one field, where the spiked European
      dataset-based RF calibration models outperformed the corresponding GBM and ANN
      models. In the second field ANN has replaced RF in being the best performing.
      However, the local field calibrations provided lower R2 and RPD in most cases.
      Therefore, from a cost-effective point of view, it is recommended to adopt the
      spiked European dataset-based RF/ANN calibration models for successful prediction
      of TN and TC under on-line measurement conditions.

PMID- 29064412
TI  - Development and Elucidation of a Novel Fluorescent Boron-Sensor for the Analysis
      of Boronic Acid-Containing Compounds.
AB  - Novel boron-containing drugs have recently been suggested as a new class of
      pharmaceuticals. However, the majority of current boron-detection techniques
      require expensive facilities and/or tedious pretreatment methods. Thus, to
      develop a novel and convenient detection method for boron-based pharmaceuticals,
      imine-type boron-chelating-ligands were previously synthesized for use in a
      fluorescent sensor for boronic acid containing compounds. However, the
      fluorescence quantum yield of the imine-type sensor was particularly low, and the
      sensor was easily decomposed in aqueous media. Thus, in this paper, we report the
      development of a novel, convenient, and stable fluorescent boron-sensor based on
      O- and N-chelation (i.e., 2-(pyridine-2yl)phenol), and a corresponding method for
      the quantitative and qualitative detection of boronic acid-containing compounds
      using this commercially available sensor is presented.

PMID- 29064413
TI  - Enhanced Efficiency in Dye-Sensitized Solar Cells by Electron Transport and Light
      Scattering on Freestanding TiO2 Nanotube Arrays.
AB  - Dye-sensitized solar cells (DSSCs) were fabricated with closed- or open-ended
      freestanding TiO2 nanotube arrays as photoelectrodes that were decorated with
      carbon materials and large TiO2 nanoparticles (NPs) to enhance energy conversion
      efficiency. The energy conversion efficiency of DSSCs based on open-ended
      freestanding TiO2 nanotube arrays increased from 4.47% to 5.39%, compared to the
      DSSCs based on closed-ended freestanding TiO2 nanotube arrays. In DSSCs based on
      the open-ended freestanding TiO2 nanotube arrays, the energy conversion
      efficiency with carbon materials increased from 5.39% to 6.19% due to better
      electron transport, and that with a scattering layer from 5.39% to 6.24% due to
      more light harvesting compared to the DSSCs without carbon materials or
      scattering layer. Moreover, the energy conversion efficiency of DSSCs based on
      the open-ended freestanding TiO2 nanotube arrays with both carbon materials and
      scattering layer increased from 5.39% to 6.98%, which is an enhancement of
      29.50%. In DSSCs based on the TiO2 nanotube arrays, the carbon materials can
      improve electron transport by pi-pi conjugation, and the large TiO2 NPs can
      enhance the capacity to light-harvest by scattering.

PMID- 29064414
TI  - Effects of In Utero Exposure to Di-n-Butyl Phthalate on Testicular Development in
      Rat.
AB  - Humans are inevitably exposed to ubiquitous phthalate esters (PAEs). In utero
      exposure to di-n-butyl phthalate (DBP) induces abnormal development of the testis
      and reproductive tract in male offspring, which correspond closely with the human
      condition of testicular dysgenesis syndrome (TDS)-like syndrome. However, the
      underlying mechanisms have not been elucidated in detail. In this study, pregnant
      rats were orally exposed to either corn oil (controls) or DBP at three different
      doses by gavage during Gestational Days 12.5-21.5. Pathological examinations were
      performed for toxicity evaluation. Proliferation and apoptosis related proteins
      (ras related dexamethasone induced 1 (Rasd1), mitogen-activated protein kinase
      kinases1/2 (MEK1/2), Bcl-2, and Bax) were measured for mechanisms exploration.
      The results showed that different doses of DBP caused male developmental and
      reproductive toxicity in rats, including the decrease of anogenital distance
      (AGD), the histological damage of testis, and apoptosis of seminiferous tubule
      cells. Our data suggested that DBP played chronic and continuous toxic roles on
      male reproductive system by disrupting expression of Rasd1 and MEK1/2 as well as
      Bcl-2/Bax ratio. Further research is warranted.

PMID- 29064415
TI  - Solitary Intra-Osseous Myofibroma of the Jaw: A Case Report and Review of
      Literature.
AB  - Myofibroma is a rare benign spindle cell neoplasm in children that usually
      affects both soft tissue and bone in the head and neck region. Approximately one
      third of these cases are seen within jaw bones as solitary lesions. Solitary
      intra-osseous myofibroma of the jaw bone shares its clinical, radiographic and
      histological features with other spindle cell tumors. The rarity of this lesion
      can make diagnosis difficult for clinicians and pathologists. We report a case of
      a solitary intra-osseous myofibroma in the mandible of a nine-year-old child.

PMID- 29064416
TI  - A Novel Unsupervised Segmentation Quality Evaluation Method for Remote Sensing
      Images.
AB  - The segmentation of a high spatial resolution remote sensing image is a critical
      step in geographic object-based image analysis (GEOBIA). Evaluating the
      performance of segmentation without ground truth data, i.e., unsupervised
      evaluation, is important for the comparison of segmentation algorithms and the
      automatic selection of optimal parameters. This unsupervised strategy currently
      faces several challenges in practice, such as difficulties in designing effective
      indicators and limitations of the spectral values in the feature representation.
      This study proposes a novel unsupervised evaluation method to quantitatively
      measure the quality of segmentation results to overcome these problems. In this
      method, multiple spectral and spatial features of images are first extracted
      simultaneously and then integrated into a feature set to improve the quality of
      the feature representation of ground objects. The indicators designed for spatial
      stratified heterogeneity and spatial autocorrelation are included to estimate the
      properties of the segments in this integrated feature set. These two indicators
      are then combined into a global assessment metric as the final quality score. The
      trade-offs of the combined indicators are accounted for using a strategy based on
      the Mahalanobis distance, which can be exhibited geometrically. The method is
      tested on two segmentation algorithms and three testing images. The proposed
      method is compared with two existing unsupervised methods and a supervised method
      to confirm its capabilities. Through comparison and visual analysis, the results
      verified the effectiveness of the proposed method and demonstrated the
      reliability and improvements of this method with respect to other methods.

PMID- 29064417
TI  - Precise GNSS Positioning Using Smart Devices.
AB  - The recent access to GNSS (Global Navigation Satellite System) phase observations
      on smart devices, enabled by Google through its Android operating system, opens
      the possibility to apply precise positioning techniques using off-the-shelf, mass
      market devices. The target of this work is to evaluate whether this is feasible,
      and which positioning accuracy can be achieved by relative positioning of the
      smart device with respect to a base station. Positioning of a Google/HTC Nexus 9
      tablet was performed by means of batch least-squares adjustment of L1 phase
      double-differenced observations, using the open source goGPS software, over
      baselines ranging from approximately 10 m to 8 km, with respect to both physical
      (geodetic or low-cost) and virtual base stations. The same positioning procedure
      was applied also to a co-located u-blox low-cost receiver, to compare the
      performance between the receiver and antenna embedded in the Nexus 9 and a
      standard low-cost single-frequency receiver with external patch antenna. The
      results demonstrate that with a smart device providing raw GNSS phase
      observations, like the Nexus 9, it is possible to reach decimeter-level accuracy
      through rapid-static surveys, without phase ambiguity resolution. It is expected
      that sub-centimeter accuracy could be achieved, as demonstrated for the u-blox
      case, if integer phase ambiguities were correctly resolved.

PMID- 29064418
TI  - Effect of Clostridium perfringens beta-Toxin on Platelets.
AB  - Clostridium perfringensbeta-toxin (CPB) is the major virulence factor of
      C.perfringens type C causing a hemorrhagic enteritis in animals and humans. In
      experimentally infected pigs, endothelial binding of CPB was shown to be
      associated with early vascular lesions and hemorrhage but without obvious
      thrombosis of affected vessels, suggesting altered hemostasis in the early phase
      of the disease. The objective of the present study was to investigate the effect
      of CPB on platelets, with respect to primary hemostasis. Our results demonstrate
      that CPB binds to porcine and human platelets and forms oligomers resulting in a
      time- and dose-dependent cell death. Platelets showed rapid ultrastructural
      changes, significantly decreased aggregation and could no longer be activated by
      thrombin. This indicates that CPB affects the physiological function of platelets
      and counteracts primary hemostasis. Our results add platelets to the list of
      target cells of CPB and extend the current hypothesis of its role in the
      pathogenesis of C. perfringens type C enteritis.

PMID- 29064419
TI  - Ni(II) Complexes with Schiff Base Ligands: Preparation, Characterization,
      DNA/Protein Interaction and Cytotoxicity Studies.
AB  - In this study, two Ni(II) complexes, namely [Ni(HL1)2(OAc)2] (1) and [Ni(L2)2]
      (2) (where HL1 and HL2 are (E)-1-((1-(2-hydroxyethyl)-1H-pyrazol-5
      ylimino)methyl)-naphthalen-2-ol) and (E)-ethyl-5-((2-hydroxynaphthalen-1
      yl)methyleneamino)-1-methyl-1H-pyrazole-4-carboxylate, respectively), were
      synthesized and characterized by X-ray crystallography, Electrospray Ionization
      Mass Spectrometry (ESI-MS), elemental analysis, and IR. Their uptake in
      biological macromolecules and cancer cells were preliminarily investigated
      through electronic absorption (UV-Vis), circular dichroism (CD) and fluorescence
      quenching measurements. Bovine serum albumin (BSA) interaction experiments were
      investigated by spectroscopy which showed that the complexes and ligands could
      quench the intrinsic fluorescence of BSA through an obvious static quenching
      process. The spectroscopic studies indicated that these complexes could bind to
      DNA via groove, non-covalent, and electrostatic interactions. Furthermore, in
      vitro methyl thiazolyl tetrazolium (MTT) assays and Annexin V/PI flow cytometry
      experiments were performed to assess the antitumor capacity of the complexes
      against eight cell lines. The results show that both of the complexes possess
      reasonable cytotoxicities.

PMID- 29064420
TI  - Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications.
AB  - The immune system has a substantial effect on colorectal cancer (CRC)
      progression. Additionally, the response to immunotherapeutics and conventional
      treatment options (e.g., chemotherapy, radiotherapy and targeted therapies) is
      influenced by the immune system. The molecular characterization of colorectal
      cancer (CRC) has led to the identification of favorable and unfavorable
      immunological attributes linked to clinical outcome. With the definition of
      consensus molecular subtypes (CMSs) based on transcriptomic profiles, multiple
      characteristics have been proposed to be responsible for the development of the
      tumor immune microenvironment and corresponding mechanisms of immune escape. In
      this review, a detailed description of proposed immune phenotypes as well as
      their interaction with different therapeutic modalities will be provided.
      Finally, possible strategies to shift the CRC immune phenotype towards a
      reactive, anti-tumor orientation are proposed per CMS.

PMID- 29064422
TI  - Systemic Interleukin-4 Administration after Spinal Cord Injury Modulates
      Inflammation and Promotes Neuroprotection.
AB  - Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in
      the motor, sensory and autonomic systems. The severe inflammatory reaction that
      occurs after SCI is strongly associated with further tissue damage. As such,
      immunomodulatory strategies have been developed, aimed at reducing inflammation,
      but also at shaping the immune response in order to protect, repair and promote
      regeneration of spared neural tissue. One of those promising strategies is the
      intraspinal administration of the cytokine interleukin-4 (IL-4) that was shown to
      promote a phenotype on specific immune cells associated with neuroprotection and
      repair. In this work, we evaluated if a systemic delivery of IL-4 for a 7-days
      period was also capable of promoting neuroprotection after SCI by analyzing
      different neural cells populations and motor recovery. IL-4 treatment promoted an
      elevation of the anti-inflammatory cytokine IL-10 in the serum both at 24 h and 7
      days after injury. Locally, treatment with IL-4 led to a reduction on cells
      expressing markers associated with inflammation, CD11b/c and iNOS. Importantly,
      IL-4 treatment increased the neuronal markers betaIII-tubulin and NeuN, and the
      oligodendrocyte marker O4, suggesting a neuroprotective effect. Moreover, 100% of
      the animals treated with IL-4 were able to recover weight support against only
      33% of saline treated animals. Overall, these results show that systemic
      administration of IL-4 positively impacts different aspects of spinal cord
      injury, creating a more favorable environment for recovery to take place.

PMID- 29064421
TI  - Muscle-Bone Crosstalk: Emerging Opportunities for Novel Therapeutic Approaches to
      Treat Musculoskeletal Pathologies.
AB  - Osteoporosis and sarcopenia are age-related musculoskeletal pathologies that
      often develop in parallel. Osteoporosis is characterized by a reduced bone mass
      and an increased fracture risk. Sarcopenia describes muscle wasting with an
      increasing risk of injuries due to falls. The medical treatment of both diseases
      costs billions in health care per year. With the impact on public health and
      economy, and considering the increasing life expectancy of populations, more
      efficient treatment regimens are sought. The biomechanical interaction between
      both tissues with muscle acting on bone is well established. Recently, both
      tissues were also determined as secretory endocrine organs affecting the function
      of one another. New exciting discoveries on this front are made each year, with
      novel signaling molecules being discovered and potential controversies being
      described. While this review does not claim completeness, it will summarize the
      current knowledge on both the biomechanical and the biochemical link between
      muscle and bone. The review will highlight the known secreted molecules by both
      tissues affecting the other and finish with an outlook on novel therapeutics that
      could emerge from these discoveries.

PMID- 29064424
TI  - Synthesis and Antitumor Activity of Triazole-Containing Sorafenib Analogs.
AB  - Using a highly effective binuclear Cu complex as the catalyst, the 1,3-dipolar
      cycloaddition reactions between 16 alkynes and two azides were successfully
      performed and resulted in the production of 25 new triazole-containing sorafenib
      analogs. Several compounds were evaluated as potent antitumor agents. Among them,
      4-(4-(4-(3-fluorophenyl)-1H-1,2,3-triazol-1-yl)phenoxy)-N-methylpicolinamide (8f)
      potently suppressed the proliferation of HT-29 cancer cells by inducing apoptosis
      and almost completely inhibited colony formation at a low micromolar
      concentration.

PMID- 29064425
TI  - Hydrogen Sulfide Releasing 2-Mercaptoacrylic Acid-Based Derivative Possesses
      Cytoprotective Activity in a Small Intestine of Rats with Medication-Induced
      Enteropathy.
AB  - Small intestinal injury is known to be one of the most commonly appearing
      pathologies, resulting in the use of medications such as: nonsteroidal anti
      inflammatory drugs (NSAIDs), antitumor drugs and angiotensin-converting enzyme
      (ACE) inhibitors. The principal objective of this study is to evaluate the action
      of a novel mercaptoacrylic acid derivative able to release H2S on parameters of
      NO-synthase system and oxidative stress. Inducing enteropathy, three types of
      medications were used: indomethacin, an NSAID (35 mg/kg); methotrexate, an
      antitumor drug (10 mg/kg); and enalapril, an ACE inhibitor (2 mg/kg/day). 2-[(4
      chlorophenyl-carbamoyl)-methyl]-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-acrylic
      acid (2C3DHTA) was introduced based on the background of medication-induced
      enteropathy (10 mg/kg/day). The survey showed that malondialdehyde (MDA)
      concentration, myeloperoxidase (MPO) activity, superoxide dismutase (SOD),
      catalase, and NO-synthases (NOS) were determined in the small intestinal mucosa.
      The increase in inducible NO-synthase (iNOS) activity was due to indomethacin and
      methotrexate administration. Constitutive NO-synthase (cNOS) activity was
      decreased by an ACE-inhibitor. The cytoprotective effect was demonstrated by
      2C3DHTA, which returned iNOS activity to its control level and increased cNOS
      activity. The enterotoxic action of studied medication was accompanied by the
      development of oxidative stress manifested, activity of MPO was increased. MPO
      activity and manifestations of oxidative stress were decreased by 2C3DHTA.
      Effects of 2C3DHTA can be explained by the action of H2S, released from this
      compound in the gastrointestinal (GI) system.

PMID- 29064423
TI  - Targeting PDK1 for Chemosensitization of Cancer Cells.
AB  - Despite the rapid development in the field of oncology, cancer remains the second
      cause of mortality worldwide, with the number of new cases expected to more than
      double in the coming years. Chemotherapy is widely used to decelerate or stop
      tumour development in combination with surgery or radiation therapy when
      appropriate, and in many cases this improves the symptomatology of the disease.
      Unfortunately though, chemotherapy is not applicable to all patients and even
      when it is, there are many cases where a successful initial treatment period is
      followed by chemotherapeutic drug resistance. This is caused by a number of
      reasons, ranging from the genetic background of the patient (innate resistance)
      to the formation of tumour-initiating cells (acquired resistance). In this
      review, we discuss the potential role of PDK1 in the development of
      chemoresistance in different types of malignancy, and the design and application
      of potent inhibitors which can promote chemosensitization.

PMID- 29064426
TI  - Stress and the HPA Axis: Balancing Homeostasis and Fertility.
AB  - An organism's reproductive fitness is sensitive to the environment, integrating
      cues of resource availability, ecological factors, and hazards within its
      habitat. Events that challenge the environment of an organism activate the
      central stress response system, which is primarily mediated by the hypothalamic
      pituitary-adrenal (HPA) axis. The regulatory functions of the HPA axis govern the
      cardiovascular and metabolic system, immune functions, behavior, and
      reproduction. Activation of the HPA axis by various stressors primarily inhibits
      reproductive function and is able to alter fetal development, imparting a
      biological record of stress experienced in utero. Clinical studies and
      experimental data indicate that stress signaling can mediate these effects
      through direct actions in the brain, gonads, and embryonic tissues. This review
      focuses on the mechanisms by which stress activation of the HPA axis impacts
      fertility and fetal development.

PMID- 29064427
TI  - The MEK Inhibitors Trametinib and Cobimetinib Induce a Type I Interferon Response
      in Human Keratinocytes.
AB  - Mitogen-activated protein kinase kinases (MEK) 1 and 2 have crucial roles in
      tumorigenesis, cell proliferation, and protection from apoptosis, and their
      inhibition is therefore an attractive therapeutic strategy in cancer. Orally
      available and highly selective MEK inhibitors have been developed and assessed in
      numerous clinical trials, either alone or in combination with cytotoxic
      chemotherapy and/or other targeted agents. Of note, a complex picture of class
      specific adverse effects associates with these drugs, frequently including
      inflammatory skin rash. Here, we investigated the response of normal human
      keratinocytes to the MEK inhibitors trametinib and cobimetinib, alone and in
      combination with the v-Raf murine sarcoma viral oncogene homolog B (BRAF)
      inhibitors dabrafenib and vemurafenib, in terms of signal transduction and de
      novo gene expression. MEK inhibitors triggered enhanced expression of interferon
      regulatory factor 1 (IRF1) and phosphorylation of signal transducer and activator
      of transcription 1 (STAT1), and up-regulated the keratinocyte-specific type I
      interferon kappa (IFN-kappa), the anti-viral effectors interferon-induced
      tetratricopeptide repeats (IFIT) 1 and 2, and the pro-inflammatory chemokine (C-C
      motif) ligand 2 (CCL2) and the C-X-C motif chemokine 10 (CXCL10), both at the
      mRNA and protein level. Impairment of IRF1 expression, or abrogation of STAT1
      phosphorylation due to IFN-kappa gene silencing, suppressed anti-viral and pro
      inflammatory gene expression. These data suggest that, similar to what we
      observed for epidermal growth factor receptor (EGFR) blockade, MEK inhibition
      activates a type I interferon response, which is now recognized as an effective
      anti-cancer response, in human epidermal keratinocytes.

PMID- 29064428
TI  - Diurnal Hypothalamic-Pituitary-Adrenal Axis Measures and Inflammatory Marker
      Correlates in Major Depressive Disorder.
AB  - Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory
      systems is a consistent finding in patients with Major Depressive Disorder (MDD).
      Cortisol is often assessed by measurement of the cortisol awakening response
      (CAR) and/or diurnal cortisol levels. Some methods of cortisol measurement
      overestimate cortisol concentration due to detection of other glucocorticoids
      including the relatively inert cortisone, therefore this study aimed to assess
      the presence of both cortisol and cortisone, and the cortisol-cortisone
      catalyzing enzyme 11beta-hydroxysteroiddehydrogenase type 1 (11beta-HSD1), in
      depressed patients and controls. Because the HPA axis is known to regulate the
      body's immune system, relationships between measures of cytokines and cortisol
      were also assessed. Saliva samples were collected from 57 MDD patients and 40
      healthy controls at five post-wakening time points (0, +30, +60, +720 and +750
      min). Glucocorticoid concentrations were measured by liquid chromatography mass
      spectrometry. Whole blood mRNA expression of several inflammatory markers was
      measured by quantitative polymerase chain reaction. This study replicated the
      common finding of elevated morning cortisol and reduced CAR reactivity in MDD and
      found no differences in cortisone or 11beta-HSD1 mRNA measures. There was a
      negative association between interleukin 1-beta (IL-1beta) mRNA and morning
      cortisol reactivity within the depressed group, indicating that dysregulation of
      the HPA axis and immune system may be interconnected.

PMID- 29064430
TI  - Nature Elements and Fundamental Motor Skill Development Opportunities at Five
      Elementary School Districts in British Columbia.
AB  - : The majority of Canadian children are not physically active enough for healthy
      development. School playgrounds are a primary location to promote physical
      activity and motor skill practice. The benefits of children's play in nature have
      also been highlighted, but few studies have evaluated children's access and
      exposure to nature for play on school grounds. This study examined children's
      access to nature on school grounds and the opportunities afforded by those
      natural elements for motor skill practice. RESULTS: Extensive naturescapes
      (multiple nature elements in one setting) were not common, and natural elements
      were limited, ranging from 1.97 to 5.71 elements/school. The most common element
      was a forested area (26.5% of all natural elements identified). In comparison to
      built structures, the number of natural elements was low. Some elements differed
      between school districts and appeared to be related to local geography and
      terrain (hilly, rocky terrain, tidal flats, etc.). Our assessment showed that
      naturescape elements afforded opportunities for the development of some key
      fundamental motor skills (FMS), specifically, locomotor and stability skills, but
      opportunities to develop manipulative skills were limited. To maximize potential
      FMS development, physical literacy, and psycho-social benefits, additional
      elements or more comprehensive multi-element naturescapes and facilitation
      (social or environmental) are recommended.

PMID- 29064431
TI  - Release Behavior and Antibacterial Activity of Chitosan/Alginate Blends with Aloe
      vera and Silver Nanoparticles.
AB  - Aloe vera is a perennial plant employed for medical, pharmaceutical and cosmetic
      purposes that is rich in amino acids, enzymes, vitamins and polysaccharides,
      which are responsible for its therapeutic properties. Incorporating these
      properties into a biopolymer film obtained from alginate and chitosan allowed the
      development of a novel wound dressing with antibacterial capacity and healing
      effects to integrate the antibacterial capacity of silver nanoparticles with the
      healing and emollient properties of Aloe vera gel. Three alginate-chitosan
      matrices were obtained through blending methods using different proportions of
      alginate, chitosan, the Aloe vera (AV) gel and silver nanoparticles (AgNps),
      which were incorporated into the polymeric system through immersion methods.
      Physical, chemical and antibacterial characteristics were evaluated in each
      matrix. Interaction between alginate and chitosan was identified using the
      Fourier transform infrared spectroscopy technique (FTIR), porosity was studied
      using scanning electron microscopy (SEM), swelling degree was calculated by
      difference in weight, Aloe vera gel release capacity was estimated by applying a
      drug model (Peppas) and finally antibacterial capacity was evaluated against S.
      Aureus and P. aeruginosa. Results show that alginate-chitosan (A (1:3 Chit 1/Alg
      1); B (1:3 Chit 1.5/Alg 1) and C (3:1 Chit 1/Alg 1/B12)) matrices with Aloe vera
      (AV) gel and silver nanoparticles (AgNps) described here displayed antibacterial
      properties and absorption and Aloe vera release capacity making it a potential
      wound dressing for minor injuries.

PMID- 29064433
TI  - Short Review on Predicting Fouling in RO Desalination.
AB  - Reverse Osmosis (RO) membrane fouling is one of the main challenges that membrane
      manufactures, the scientific community and industry professionals have to deal
      with. The consequences of this inevitable phenomenon have a negative effect on
      the performance of the desalination system. Predicting fouling in RO systems is
      key to evaluating the long-term operating conditions and costs. Much research has
      been done on fouling indices, methods, techniques and prediction models to
      estimate the influence of fouling on the performance of RO systems. This paper
      offers a short review evaluating the state of industry knowledge in the
      development of fouling indices and models in membrane systems for desalination in
      terms of use and applicability. Despite major efforts in this field, there are
      gaps in terms of effective methods and models for the estimation of fouling in
      full-scale RO desalination plants. In existing models applied to full-scale RO
      desalination plants, neither the spacer geometry of membranes, nor the efficiency
      and frequency of chemical cleanings are considered.

PMID- 29064429
TI  - Zinc Signals and Immunity.
AB  - Zinc homeostasis is crucial for an adequate function of the immune system. Zinc
      deficiency as well as zinc excess result in severe disturbances in immune cell
      numbers and activities, which can result in increased susceptibility to
      infections and development of especially inflammatory diseases. This review
      focuses on the role of zinc in regulating intracellular signaling pathways in
      innate as well as adaptive immune cells. Main underlying molecular mechanisms and
      targets affected by altered zinc homeostasis, including kinases, caspases,
      phosphatases, and phosphodiesterases, will be highlighted in this article. In
      addition, the interplay of zinc homeostasis and the redox metabolism in affecting
      intracellular signaling will be emphasized. Key signaling pathways will be
      described in detail for the different cell types of the immune system. In this,
      effects of fast zinc flux, taking place within a few seconds to minutes will be
      distinguish from slower types of zinc signals, also designated as "zinc waves",
      and late homeostatic zinc signals regarding prolonged changes in intracellular
      zinc.

PMID- 29064432
TI  - Chromosome Evolution in Connection with Repetitive Sequences and Epigenetics in
      Plants.
AB  - Chromosome evolution is a fundamental aspect of evolutionary biology. The
      evolution of chromosome size, structure and shape, number, and the change in DNA
      composition suggest the high plasticity of nuclear genomes at the chromosomal
      level. Repetitive DNA sequences, which represent a conspicuous fraction of every
      eukaryotic genome, particularly in plants, are found to be tightly linked with
      plant chromosome evolution. Different classes of repetitive sequences have
      distinct distribution patterns on the chromosomes. Mounting evidence shows that
      repetitive sequences may play multiple generative roles in shaping the chromosome
      karyotypes in plants. Furthermore, recent development in our understanding of the
      repetitive sequences and plant chromosome evolution has elucidated the
      involvement of a spectrum of epigenetic modification. In this review, we focused
      on the recent evidence relating to the distribution pattern of repetitive
      sequences in plant chromosomes and highlighted their potential relevance to
      chromosome evolution in plants. We also discussed the possible connections
      between evolution and epigenetic alterations in chromosome structure and
      repatterning, such as heterochromatin formation, centromere function, and
      epigenetic-associated transposable element inactivation.

PMID- 29064434
TI  - Towards Harmonious Coexistence in the Unlicensed Spectrum: Rational Cooperation
      of Operators.
AB  - 5G New Radio (NR) operating in the unlicensed spectrum is accelerating the Fourth
      Industrial Revolution by supporting Internet of Things (IoT) networks or
      Industrial IoT deployments. Specifically, LTE-Advanced (LTE-A) is looking to
      achieve spectrum integration through coexistence with multi-radio access
      technology (RAT) systems in the same unlicensed bands with both licensed-assisted
      and stand-alone access. The listen-before-talk (LBT) mechanism is mainly
      considered to enable an LTE operator to protect other incumbent unlicensed
      systems. In this article, we investigate the behaviors of multiple LTE operators
      along with the deployment of WiFi networks in the unlicensed spectrum from both
      short- and long-term points of view. In countries without mandatory LBT
      requirements, we show that an LTE operator is susceptible to collusion with
      another LTE operator, thus exploiting scarce spectrum resources by deceiving
      other wireless networks into thinking that channels are always busy; hence,
      mandatory usage of LTE with LBT is highly recommended at national level to
      achieve harmonious coexistence in the unlicensed spectrum. We discuss several
      possible coexistence scenarios to resolve the operator's dilemmaas well as to
      improve unlicensed spectrum efficiency among multi-RAT systems, which is viable
      in the near future.

PMID- 29064435
TI  - Effect of Wafer Level Underfill on the Microbump Reliability of Ultrathin-Chip
      Stacking Type 3D-IC Assembly during Thermal Cycling Tests.
AB  - The microbump (MU-bump) reliability of 3D integrated circuit (3D-IC) packaging
      must be enhanced, in consideration of the multi-chip assembly, during temperature
      cycling tests (TCT). This research proposes vehicle fabrications, experimental
      implements, and a nonlinear finite element analysis to systematically investigate
      the assembled packaging architecture that stacks four thin chips through the
      wafer level underfill (WLUF) process. The assembly of MU-bump interconnects by
      daisy chain design shows good quality. Results of both TCT data and the
      simulation indicate that MU-bumps with residual SnAg solders can reach more than
      1200 fatigue life cycles. Moreover, several important design factors in the
      present 3D-IC package influence MU-bump reliability. Analytical results show that
      the MU-bump's thermo-mechanical reliability can be improved by setting proper
      chip thickness, along with a WLUF that has a low elastic modulus and a small
      coefficient of thermal expansion.

PMID- 29064436
TI  - Modelling of Hydrophilic Interaction Liquid Chromatography Stationary Phases
      Using Chemometric Approaches.
AB  - Metabolomics is a powerful and widely used approach that aims to screen
      endogenous small molecules (metabolites) of different families present in
      biological samples. The large variety of compounds to be determined and their
      wide diversity of physical and chemical properties have promoted the development
      of different types of hydrophilic interaction liquid chromatography (HILIC)
      stationary phases. However, the selection of the most suitable HILIC stationary
      phase is not straightforward. In this work, four different HILIC stationary
      phases have been compared to evaluate their potential application for the
      analysis of a complex mixture of metabolites, a situation similar to that found
      in non-targeted metabolomics studies. The obtained chromatographic data were
      analyzed by different chemometric methods to explore the behavior of the
      considered stationary phases. ANOVA-simultaneous component analysis (ASCA),
      principal component analysis (PCA) and partial least squares regression (PLS)
      were used to explore the experimental factors affecting the stationary phase
      performance, the main similarities and differences among chromatographic
      conditions used (stationary phase and pH) and the molecular descriptors most
      useful to understand the behavior of each stationary phase.

PMID- 29064437
TI  - The Assessment of Toxic Metals in Plants Used in Cosmetics and Cosmetology.
AB  - Heavy metals polluting the natural environment are absorbed by plants. The use of
      herbs as components of cosmetics may pose a health risk for humans. The aim of
      the study was to determine the concentrations of Pb, Cd and Hg in selected
      species of herbs (horsetail Equisetum arvense, nettle Urtica dioica, St. John's
      wort Hypericum perforatum, wormwood Artemisia absinthium, yarrow Achillea
      millefolium, cottonwood Solidago virgaurea) self-collected from the natural
      environment in two different locations, and purchased in stores on the territory
      of Poland. The concentration of the metals studied was: 4.67-23.8 mg/kg Pb, 0.01
      1.51 mg/kg Cd, 0.005-0.028 mg/kg Hg. Different concentrations of metals,
      depending on species and origin of plants, were found. The mean concentration of
      all studied metals was the lowest in St. John's wort, and the highest in nettle.
      In herbs purchased in Polish stores, the concentration of Pb was higher than in
      plants self-collected in the natural environment.

PMID- 29064438
TI  - Planar Microstrip Ring Resonators for Microwave-Based Gas Sensing: Design Aspects
      and Initial Transducers for Humidity and Ammonia Sensing.
AB  - A planar microstrip ring resonator structure on alumina was developed using the
      commercial FEM software COMSOL. Design parameters were evaluated, eventually
      leading to an optimized design of a miniaturized microwave gas sensor. The sensor
      was covered with a zeolite film. The device was successfully operated at around
      8.5 GHz at room temperature as a humidity sensor. In the next step, an additional
      planar heater will be included on the reverse side of the resonator structure to
      allow for testing of gas-sensitive materials under sensor conditions.

PMID- 29064440
TI  - Psycho-Physiological Associates of Dyspnea in Hospitalized Patients with
      Interstitial Lung Diseases: A Cross-Sectional Study.
AB  - Dyspnea has been found to be an independent predictor of mortality among patients
      with respiratory diseases and is often regarded as a difficult symptom to control
      in patients with interstitial lung diseases (ILDs). Previous studies have found
      an association of psychological and physiological factors with dyspnea among
      patients with chronic obstructive airway diseases. However, symptom management of
      hospitalized patients with ILDs has been hampered by difficulty in priority,
      since they are often admitted with multiple psycho-physiological needs. This
      study examined the prevalence of dyspnea and the psycho-physiological factors
      associated with it among hospitalized Chinese patients with ILDs. We studied 165
      hospitalized patients with ILDs recruited consecutively over three months in a
      public hospital in Guangzhou, China. Dyspnea and common psycho-physiological
      factors, including cough symptoms, activity capacity, lung function, physical and
      mental health status, and anxiety and depression symptoms, were measured. By
      ordered logistic regression, level of dyspnea statistically significantly
      affected performance in a six-minute walk test and physical functioning in work
      or other regular daily activities in hospitalized patients with ILDs. Respiratory
      rehabilitation with an appropriate intensity of exercise training or other
      strategies for enhancing the physical functioning of this population with
      moderate and severe levels of dyspnea should be prioritized.

PMID- 29064439
TI  - Roles of microRNAs and RNA-Binding Proteins in the Regulation of Colorectal
      Cancer Stem Cells.
AB  - Colorectal cancer stem cells (CSCs) are responsible for the initiation,
      progression and metastasis of human colorectal cancers, and have been
      characterized by the expression of cell surface markers, such as CD44, CD133,
      CD166 and LGR5. MicroRNAs (miRNAs) are differentially expressed between CSCs and
      non-tumorigenic cancer cells, and play important roles in the maintenance and
      regulation of stem cell properties of CSCs. RNA binding proteins (RBPs) are
      emerging epigenetic regulators of various RNA processing events, such as
      splicing, localization, stabilization and translation, and can regulate various
      types of stem cells. In this review, we summarize current evidences on the roles
      of miRNA and RBPs in the regulation of colorectal CSCs. Understanding the
      epigenetic regulation of human colorectal CSCs will help to develop biomarkers
      for colorectal cancers and to identify targets for CSC-targeting therapies.

PMID- 29064442
TI  - Enhanced Glucose Uptake in Human Liver Cells and Inhibition of Carbohydrate
      Hydrolyzing Enzymes by Nordic Berry Extracts.
AB  - A Western lifestyle with low physical activity and a diet rich in sugar, fat and
      processed food contribute to higher incidences of diabetes and obesity. Enhanced
      glucose uptake in human liver cells was observed after treatment with phenolic
      extracts from different Nordic berries. All berry extracts showed higher
      inhibition against alpha-amylase and alpha-glucosidase than the anti-diabetic
      agent acarbose. Total phenolic content and phenolic profiles in addition to
      antioxidant activities, were also investigated. The berries were extracted with
      80% methanol on an accelerated solvent extraction system (ASE) and then purified
      by C-18 solid phase extraction (SPE). Among the ASE methanol extracts, black
      chokeberry, crowberry and elderberry extracts showed high stimulation of glucose
      uptake in HepG2 cells and also considerable inhibitory effect towards
      carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of
      phenolics, resulted in increased glucose uptake and enhanced inhibition of alpha
      amylase and alpha-glucosidase compared to the ASE extracts. Crowberry and
      cloudberry were the most potent 15-lipoxygenase inhibitors, while bog
      whortleberry and lingonberry were the most active xanthine oxidase inhibitors.
      These results increase the value of these berries as a component of a healthy
      Nordic diet and have a potential benefit against diabetes.

PMID- 29064443
TI  - The Relationship between Starting to Drink and Psychological Distress, Sleep
      Disturbance after the Great East Japan Earthquake and Nuclear Disaster: The
      Fukushima Health Management Survey.
AB  - This longitudinal study aimed to investigate the prevalence of newly-started
      drinkers and their continuing drinking behaviors after the Great East Japan
      earthquake. Moreover, the relationships between newly-started drinking and
      psychological factor, disaster-related experience, and perceived radiation risk
      were examined. We used data from 37,687 pre-disaster non-drinkers who
      participated in the 2012 and 2013 surveys conducted in Fukushima. We defined
      newly-started drinkers as those who did not drink before the disaster but who
      began drinking after the disaster, based on information collected
      retrospectively. In 2012, 9.6% of non-drinkers began drinking, of which the
      prevalence of heavy drinkers was 18.4%. The prevalence of continued drinking
      among newly-started drinkers in 2013 was 53.8%. Logistic regression analyses
      revealed post-disaster newly-started drinking was significantly associated with
      being male, less than 65 years old, sleep dissatisfaction and psychological
      distress (Kessler 6 <= 13) when this model was adjusted for disaster-related
      experience and perceived radiation risk. Moreover, psychological distress and
      heavy drinking were significant risk factors for continued drinking among newly
      started drinkers. Newly-started drinkers might use alcohol to cope with disaster
      related stress. Thus, they may be targeted for disaster-related health services.
      Moreover, early intervention should encourage responsible drinking, since post
      disaster heavy drinkers were likely to continue heavy drinking.

PMID- 29064444
TI  - Design of Novel, Water Soluble and Highly Luminescent Europium Labels with
      Potential to Enhance Immunoassay Sensitivities.
AB  - To meet the continual demands of more-sensitive immunoassays, the synthesis of
      novel luminescent Eu(III) chelate labels having similar substituted 4
      (phenylethynyl)pyridine chromophores in three different chelate structure classes
      are reported. Significantly enhanced luminescence intensities were obtained,
      evidently caused by the intra-ligand charge transfer (ILCT) mediated
      sensitization, but the alternative ligands triplet state process cannot be ruled
      out. Based on the present study, even quite small changes on the chelate
      structure, and, especially, on the substituents' donor/acceptor strength on both
      ends of 4-(phenylethynyl)pyridine subunits have an unpredictable effect on the
      luminescence. The highest observed brightness was 16,400 M-1cm-1 in solution and
      69,500 M-1cm-1 on dry surface, being 3.4 and 8.7 fold higher compared to the
      reference chelate. The new label chelates provide solutions for improved assay
      sensitivity up-to tenfold from the present concepts.

PMID- 29064445
TI  - Pediatric Perioperative Pulmonary Arterial Hypertension: A Case-Based Primer.
AB  - The perioperative period is an extremely tenuous time for the pediatric patient
      with pulmonary arterial hypertension. This article will discuss a
      multidisciplinary approach to preoperative planning, the importance of early
      identification of pulmonary hypertensive crises, and practical strategies for
      postoperative management for this unique group of children.

PMID- 29064441
TI  - Pattern Recognition of the Multiple Sclerosis Syndrome.
AB  - During recent decades, the autoimmune disease neuromyelitis optica spectrum
      disorder (NMOSD), once broadly classified under the umbrella of multiple
      sclerosis (MS), has been extended to include autoimmune inflammatory conditions
      of the central nervous system (CNS), which are now diagnosable with serum
      serological tests. These antibody-mediated inflammatory diseases of the CNS share
      a clinical presentation to MS. A number of practical learning points emerge in
      this review, which is geared toward the pattern recognition of optic neuritis,
      transverse myelitis, brainstem/cerebellar and hemispheric tumefactive
      demyelinating lesion (TDL)-associated MS, aquaporin-4-antibody and myelin
      oligodendrocyte glycoprotein (MOG)-antibody NMOSD, overlap syndrome, and some yet
      to-be-defined/classified demyelinating disease, all unspecifically labeled under
      MSsyndrome. The goal of this review is to increase clinicians' awareness of the
      clinical nuances of the autoimmune conditions for MS and NMSOD, and to highlight
      highly suggestive patterns of clinical, paraclinical or imaging presentations in
      order to improve differentiation. With overlay in clinical manifestations between
      MS and NMOSD, magnetic resonance imaging (MRI) of the brain, orbits and spinal
      cord, serology, and most importantly, high index of suspicion based on pattern
      recognition, will help lead to the final diagnosis.

PMID- 29064446
TI  - Single Actin Bundle Rheology.
AB  - Bundled actin structures play an essential role in the mechanical response of the
      actin cytoskeleton in eukaryotic cells. Although responsible for crucial cellular
      processes, they are rarely investigated in comparison to single filaments and
      isotropic networks. Presenting a highly anisotropic structure, the determination
      of the mechanical properties of individual bundles was previously achieved
      through passive approaches observing bending deformations induced by thermal
      fluctuations. We present a new method to determine the bending stiffness of
      individual bundles, by measuring the decay of an actively induced oscillation.
      This approach allows us to systematically test anisotropic, bundled structures.
      Our experiments revealed that thin, depletion force-induced bundles behave as
      semiflexible polymers and obey the theoretical predictions determined by the
      wormlike chain model. Thickening an individual bundle by merging it with other
      bundles enabled us to study effects that are solely based on the number of
      involved filaments. These thicker bundles showed a frequency-dependent bending
      stiffness, a behavior that is inconsistent with the predictions of the wormlike
      chain model. We attribute this effect to internal processes and give a possible
      explanation with regard to the wormlike bundle theory.

PMID- 29064447
TI  - Investigation of Sex Differences in the Microglial Response to Binge Ethanol and
      Exercise.
AB  - The female brain appears selectively vulnerable to the neurotoxic effects of
      alcohol, but the reasons for this are unclear. One possibility is an exaggerated
      neuroimmune response in the female brain, such that alcohol increases microglia
      number and reactivity to subsequent stimuli, such as exercise. It is important to
      better characterize the interactive neural effects of alcohol and exercise, as
      exercise is increasingly being used in the treatment of alcohol use disorders.
      The present study compared the number of microglia and evidence of their
      activation in alcohol-vulnerable regions of the brain (medial prefrontal cortex
      and hippocampus) in male and female rats following binge alcohol and/or exercise.
      Binge alcohol increased microglia number and morphological characteristics
      consistent with their activation in the female brain but not the male, regardless
      of exercise. Binge alcohol followed by exercise did increase the number of MHC
      II+ (immunocompetent) microglia in females, although the vast majority of
      microglia did not express MHC II. These results indicate that binge alcohol
      exerts sex-specific effects on microglia that may result in enhanced reactivity
      to a subsequent challenge and in part underlie the apparent selective
      vulnerability of the female brain to alcohol.

PMID- 29064448
TI  - Production and Use of Hymenolepis diminuta Cysticercoids as Anti-Inflammatory
      Therapeutics.
AB  - Helminthic therapy has shown considerable promise as a means of alleviating some
      inflammatory diseases that have proven resistant to pharmaceutical intervention.
      However, research in the field has been limited by a lack of availability to
      clinician scientists of a helminth that is relatively benign, non-communicable,
      affordable, and effectively treats disease. Previous socio-medical studies have
      found that some individuals self-treating with helminths to alleviate various
      diseases are using the rat tapeworm (cysticercoid developmental stage of
      Hymenolepis diminuta; HDC). In this study, we describe the production and use of
      HDCs in a manner that is based on reports from individuals self-treating with
      helminths, individuals producing helminths for self-treatment, and physicians
      monitoring patients that are self-treating. The helminth may fit the criteria
      needed by clinical scientists for clinical trials, and the methodology is
      apparently feasible for any medical center to reproduce. It is hoped that future
      clinical trials using this organism may shed light on the potential for
      helminthic therapy to alleviate inflammatory diseases. Further, it is hoped that
      studies with HDCs may provide a stepping stone toward population-wide restoration
      of the biota of the human body, potentially reversing the inflammatory
      consequences of biota depletion that currently affect Western society.

PMID- 29064449
TI  - Molecular Affinity of Mabolo Extracts to an Octopamine Receptor of a Fruit Fly.
AB  - Essential oils extracted from plants are composed of volatile organic compounds
      that can affect insect behavior. Identifying the active components of the
      essential oils to their biochemical target is necessary to design novel
      biopesticides. In this study, essential oils extracted from Diospyros discolor
      (Willd.) were analyzed using gas chromatography mass spectroscopy (GC-MS) to
      create an untargeted metabolite profile. Subsequently, a conformational ensemble
      of the Drosophila melanogaster octopamine receptor in mushroom bodies (OAMB) was
      created from a molecular dynamics simulation to resemble a flexible receptor for
      docking studies. GC-MS analysis revealed the presence of several metabolites,
      i.e. mostly aromatic esters. Interestingly, these aromatic esters were found to
      exhibit relatively higher binding affinities to OAMB than the receptor's natural
      agonist, octopamine. The molecular origin of this observed enhanced affinity is
      the pi -stacking interaction between the aromatic moieties of the residues and
      ligands. This strategy, computational inspection in tandem with untargeted
      metabolomics, may provide insights in screening the essential oils as potential
      OAMB inhibitors.

PMID- 29064450
TI  - Equol, a Clinically Important Metabolite, Inhibits the Development and
      Pathogenicity of Magnaporthe oryzae, the Causal Agent of Rice Blast Disease.
AB  - Equol, a metabolite of soybean isoflavone daidzein, has been proven to have
      various bioactivities related to human health, but little is known on its
      antifungal activity to plant fungal pathogens. Magnaporthe oryzae is a
      phytopathogenic fungus that causes rice blast, a devastating disease on rice.
      Here, we demonstrated that equol influences the development and pathogenicity of
      M. oryzae. Equol showed a significant inhibition to the mycelial growth, conidial
      generation and germination, and appressorial formation of M. oryzae. As a result,
      equol greatly reduced the virulence of M. oryzae on rice and barley leaves. The
      antifungal activity of equol was also found in several other plant fungal
      pathogens. These findings expand our knowledge on the bioactivities of equol.

PMID- 29064451
TI  - Doing Good Again? A Multilevel Institutional Perspective on Corporate
      Environmental Responsibility and Philanthropic Strategy.
AB  - This study investigates the relationship between corporate environmental
      responsibility and corporate philanthropy. Using a sample of Chinese listed firms
      from 2008 to 2013, this paper examines the role of corporate environmental
      responsibility in corporate philanthropy and the moderating influence of the
      institutional environment using multilevel analysis. The results show that
      corporate eco-friendly events are positively associated with corporate
      philanthropic strategy to a significant degree. Provincial-level government
      intervention positively moderate the positive relationship between eco-friendly
      events and corporate philanthropy and government corruption is negatively
      moderate the relationship. All these results are robust according to robustness
      checks. These findings provide a new perspective on corporate philanthropic
      strategy as a means to obtain critical resources from the government in order to
      compensate for the loss made on environmental responsibility. Moreover, the
      institutional environment is proved here to play an important role in corporate
      philanthropic strategy.

PMID- 29064453
TI  - Accumulation and Tissue Distribution of Dinophysitoxin-1 and Dinophysitoxin-3 in
      the Mussel Crenomytilus grayanus Feeding on the Benthic Dinoflagellate
      Prorocentrum foraminosum.
AB  - A DTX-1-producing microalga, Prorocentrum foraminosum, from Peter the Great Bay,
      Sea of Japan, was fed to Gray's mussels, Crenomytilus grayanus, for 12 days. An
      increase in DTX-1 and 7-O-acyl-DTX-1 (DTX-3) was observed in the digestive gland,
      kidneys, and gills. The digestive gland accumulated 91-100% of DTX-1 + DTX-3; and
      kidneys and gills accumulated, up to 8.5% and 4.3%, respectively. The kidneys had
      a distinctive pattern of toxin accumulation where the concentration of DTX-1 did
      not grow significantly after the eighth day of feeding, indicating the potential
      of DTX-1 elimination. The digestive gland and gills predominantly accumulated DTX
      1, with a dramatic increase between Days 8 and 12. The DTX-3 content was highest
      in the digestive gland. The composition of DTX-3 in the acyl groups was similar
      for the digestive gland and kidneys, and did not change during feeding. The total
      toxin uptake of mussels exceeded the total toxin content from ingested cells by
      2.4 times, showing that toxins may have accumulated from the seawater. This
      assumption needs to be further proved. The muscle, gonads, and mantle remained
      free of toxins. No genotoxic effect was observed in the gills and digestive
      gland.

PMID- 29064454
TI  - Near-Field Three-Dimensional Planar Millimeter-Wave Holographic Imaging by Using
      Frequency Scaling Algorithm.
AB  - In this paper, a fast three-dimensional (3-D) frequency scaling algorithm (FSA)
      with large depth of focus is presented for near-field planar millimeter-wave
      (MMW) holographic imaging. Considering the cross-range range coupling term which
      is neglected in the conventional range migration algorithm (RMA), we propose an
      algorithm performing the range cell migration correction for de-chirped signals
      without interpolation by using a 3-D frequency scaling operation. First, to deal
      with the cross-range range coupling term, a 3-D frequency scaling operator is
      derived to eliminate the space variation of range cell migration. Then, a range
      migration correction factor is performed to compensate for the residual range
      cell migration. Finally, the imaging results are obtained by matched filtering in
      the cross-range direction. Compared with the conventional RMA, the proposed
      algorithm is comparable in accuracy but more efficient by using only chirp
      multiplications and fast Fourier transforms (FFTs). The algorithm has been tested
      with satisfying results by both simulation and experiment.

PMID- 29064452
TI  - Marine-Derived Penicillium Species as Producers of Cytotoxic Metabolites.
AB  - Since the discovery of penicillin, Penicillium has become one of the most
      attractive fungal genera for the production of bioactive molecules. Marine
      derived Penicillium has provided numerous excellent pharmaceutical leads over the
      past decades. In this review, we focused on the cytotoxic metabolites * (*
      Cytotoxic potency was referred to five different levels in this review,
      extraordinary (IC50/LD50: <1 MUM or 0.5 MUg/mL); significant (IC50/LD50: 1~10 MUM
      or 0.5~5 MUg/mL); moderate (IC50/LD50: 10~30 MUM or 5~15 MUg/mL); mild
      (IC50/LD50: 30~50 MUM or 15~25 MUg/mL); weak (IC50/LD50: 50~100 MUM or 25~50
      MUg/mL). The comparative potencies of positive controls were referred when they
      were available). produced by marine-derived Penicillium species, and on their
      cytotoxicity mechanisms, biosyntheses, and chemical syntheses.

PMID- 29064455
TI  - Spatiotemporal Pixelization to Increase the Recognition Score of Characters for
      Retinal Prostheses.
AB  - Most of the retinal prostheses use a head-fixed camera and a video processing
      unit. Some studies proposed various image processing methods to improve visual
      perception for patients. However, previous studies only focused on using spatial
      information. The present study proposes a spatiotemporal pixelization method
      mimicking fixational eye movements to generate stimulation images for artificial
      retina arrays by combining spatial and temporal information. Input images were
      sampled with a resolution that was four times higher than the number of pixel
      arrays. We subsampled this image and generated four different phosphene images.
      We then evaluated the recognition scores of characters by sequentially presenting
      phosphene images with varying pixel array sizes (6 * 6, 8 * 8 and 10 * 10) and
      stimulus frame rates (10 Hz, 15 Hz, 20 Hz, 30 Hz, and 60 Hz). The proposed method
      showed the highest recognition score at a stimulus frame rate of approximately 20
      Hz. The method also significantly improved the recognition score for complex
      characters. This method provides a new way to increase practical resolution over
      restricted spatial resolution by merging the higher resolution image into high
      frame time slots.

PMID- 29064457
TI  - Detection of Stress Levels from Biosignals Measured in Virtual Reality
      Environments Using a Kernel-Based Extreme Learning Machine.
AB  - Virtual reality (VR) is a computer technique that creates an artificial
      environment composed of realistic images, sounds, and other sensations. Many
      researchers have used VR devices to generate various stimuli, and have utilized
      them to perform experiments or to provide treatment. In this study, the
      participants performed mental tasks using a VR device while physiological signals
      were measured: a photoplethysmogram (PPG), electrodermal activity (EDA), and skin
      temperature (SKT). In general, stress is an important factor that can influence
      the autonomic nervous system (ANS). Heart-rate variability (HRV) is known to be
      related to ANS activity, so we used an HRV derived from the PPG peak interval. In
      addition, the peak characteristics of the skin conductance (SC) from EDA and SKT
      variation can also reflect ANS activity; we utilized them as well. Then, we
      applied a kernel-based extreme-learning machine (K-ELM) to correctly classify the
      stress levels induced by the VR task to reflect five different levels of stress
      situations: baseline, mild stress, moderate stress, severe stress, and recovery.
      Twelve healthy subjects voluntarily participated in the study. Three
      physiological signals were measured in stress environment generated by VR device.
      As a result, the average classification accuracy was over 95% using K-ELM and the
      integrated feature (IT = HRV + SC + SKT). In addition, the proposed algorithm can
      embed a microcontroller chip since K-ELM algorithm have very short computation
      time. Therefore, a compact wearable device classifying stress levels using
      physiological signals can be developed.

PMID- 29064458
TI  - CO2 Permeability of Biological Membranes and Role of CO2 Channels.
AB  - We summarize here, mainly for mammalian systems, the present knowledge of (a) the
      membrane CO2 permeabilities in various tissues; (b) the physiological
      significance of the value of the CO2 permeability;

PMID- 29064456
TI  - Reduced Abundance and Subverted Functions of Proteins in Prion-Like Diseases:
      Gained Functions Fascinate but Lost Functions Affect Aetiology.
AB  - Prions have served as pathfinders that reveal many aspects of proteostasis in
      neurons. The recent realization that several prominent neurodegenerative diseases
      spread via a prion-like mechanism illuminates new possibilities for diagnostics
      and therapeutics. Thus, key proteins in Alzheimer Disease and Amyotrophic lateral
      sclerosis (ALS), including amyloid-beta precursor protein, Tau and superoxide
      dismutase 1 (SOD1), spread to adjacent cells in their misfolded aggregated forms
      and exhibit template-directed misfolding to induce further misfolding,
      disruptions to proteostasis and toxicity. Here we invert this comparison to ask
      what these prion-like diseases can teach us about the broad prion disease class,
      especially regarding the loss of these key proteins' function(s) as they misfold
      and aggregate. We also consider whether functional amyloids might reveal a role
      for subverted protein function in neurodegenerative disease. Our synthesis
      identifies SOD1 as an exemplar of protein functions being lost during prion-like
      protein misfolding, because SOD1 is inherently unstable and loses function in its
      misfolded disease-associated form. This has under-appreciated parallels amongst
      the canonical prion diseases, wherein the normally folded prion protein, PrPC, is
      reduced in abundance in fatal familial insomnia patients and during the
      preclinical phase in animal models, apparently via proteostatic mechanisms. Thus
      while template-directed misfolding and infectious properties represent gain-of
      function that fascinates proteostasis researchers and defines (is required for)
      the prion(-like) diseases, loss and subversion of the functions attributed to
      hallmark proteins in neurodegenerative disease needs to be integrated into design
      towards effective therapeutics. We propose experiments to uniquely test these
      ideas.

PMID- 29064459
TI  - mlCAF: Multi-Level Cross-Domain Semantic Context Fusioning for Behavior
      Identification.
AB  - The emerging research on automatic identification of user's contexts from the
      cross-domain environment in ubiquitous and pervasive computing systems has proved
      to be successful. Monitoring the diversified user's contexts and behaviors can
      help in controlling lifestyle associated to chronic diseases using context-aware
      applications. However, availability of cross-domain heterogeneous contexts
      provides a challenging opportunity for their fusion to obtain abstract
      information for further analysis. This work demonstrates extension of our
      previous work from a single domain (i.e., physical activity) to multiple domains
      (physical activity, nutrition and clinical) for context-awareness. We propose
      multi-level Context-aware Framework (mlCAF), which fuses the multi-level cross
      domain contexts in order to arbitrate richer behavioral contexts. This work
      explicitly focuses on key challenges linked to multi-level context modeling,
      reasoning and fusioning based on the mlCAF open-source ontology. More
      specifically, it addresses the interpretation of contexts from three different
      domains, their fusioning conforming to richer contextual information. This paper
      contributes in terms of ontology evolution with additional domains, context
      definitions, rules and inclusion of semantic queries. For the framework
      evaluation, multi-level cross-domain contexts collected from 20 users were used
      to ascertain abstract contexts, which served as basis for behavior modeling and
      lifestyle identification. The experimental results indicate a context recognition
      average accuracy of around 92.65% for the collected cross-domain contexts.

PMID- 29064460
TI  - GC-MS Profiling of Volatile Components in Different Fermentation Products of
      Cordyceps Sinensis Mycelia.
AB  - The fermentation products of Cordyceps sinensis (C. sinensis) mycelia are
      sustainable substitutes for natural C. sinensis. However, the volatile
      compositions of the commercial products are still unclear. In this paper, we have
      developed a simultaneous distillation-extraction (SDE) and gas chromatography
      mass spectrometry (GC-MS) method for the profiling of volatile components in five
      fermentation products. A total of 64, 39, 56, 52, and 44 components were
      identified in the essential oils of Jinshuibao capsule (JSBC), Bailing capsule
      (BLC), Zhiling capsule (ZLC), Ningxinbao capsule (NXBC), and Xinganbao capsule
      (XGBC), respectively. 5,6-Dihydro-6-pentyl-2H-pyran-2-one (massoia lactone) was
      first discovered as the dominant component in JSBC volatiles. Fatty acids
      including palmitic acid (C16:0) and linoleic acid (C18:2) were also found to be
      major volatile compositions of the fermentation products. The multivariate
      partial least squares-discriminant analysis (PLS-DA) showed a clear
      discrimination among the different commercial products as well as the
      counterfeits. This study may provide further chemical evidences for the quality
      evaluation of the fermentation products of C. sinensis mycelia.

PMID- 29064462
TI  - [Reporting on Suicide. WHO recommendations for the Media.]
AB  - Inappropriate reporting on suicide in the media may lead to a contagious effect
      or "Werther effect", while appropriate characteristics may have a protective
      effect or "Papageno effect". Therefore, the media can contribute to the
      prevention of suicide. For this reason, the WHO has developed three documents
      with recommendations for media professionals about how to report on suicide.
      However, only the first one has been translated into Spanish, they have overlaps
      and have a different structure. Therefore, Spanish-speaking media professionals
      in general, and Spanish ones in particular, can hardly have access to these WHO
      recommendations displayed in a clear and concise manner. The objective of this
      work was the elaboration and provision of a single and concise text that includes
      the recommendations of these documents. A formal and structured procedure was
      followed, combining scientific and linguistic criteria. The final text contains
      the recommendations grouped into three categories: "what to do", "what not to do"
      and "other recommendations". This document can be very useful for media
      professionals, for training activities to disseminate such recommendations for
      preventive purposes, and for research.

PMID- 29064461
TI  - Endocrine Disruptors Leading to Obesity and Related Diseases.
AB  - The review aims to comprehensively present the impact of exposure to endocrine
      disruptors (EDs) in relation to the clinical manifestation of obesity and related
      diseases, including diabetes mellitus, metabolic syndrome, cardiovascular
      diseases, carcinogenesis and infertility. EDs are strong participants in the
      obesity epidemic scenery by interfering with cellular morphological and
      biochemical processes; by inducing inflammatory responses; and by presenting
      transcriptional and oncogenic activity. Obesity and lipotoxicity enhancement
      occur through reprogramming and/or remodeling of germline epigenome by exposure
      to EDs. Specific population groups are vulnerable to ED exposure due to current
      dietary and environmental conditions. Obesity, morbidity and carcinogenicity
      induced by ED exposure are an evolving reality. Therefore, a new collective
      strategic approach is deemed essential, for the reappraisal of current global
      conditions pertaining to energy management.

PMID- 29064464
TI  - A global moderate resolution dataset of gross primary production of vegetation
      for 2000-2016.
AB  - Accurate estimation of the gross primary production (GPP) of terrestrial
      vegetation is vital for understanding the global carbon cycle and predicting
      future climate change. Multiple GPP products are currently available based on
      different methods, but their performances vary substantially when validated
      against GPP estimates from eddy covariance data. This paper provides a new GPP
      dataset at moderate spatial (500 m) and temporal (8-day) resolutions over the
      entire globe for 2000-2016. This GPP dataset is based on an improved light use
      efficiency theory and is driven by satellite data from MODIS and climate data
      from NCEP Reanalysis II. It also employs a state-of-the-art vegetation index (VI)
      gap-filling and smoothing algorithm and a separate treatment for C3/C4
      photosynthesis pathways. All these improvements aim to solve several critical
      problems existing in current GPP products. With a satisfactory performance when
      validated against in situ GPP estimates, this dataset offers an alternative GPP
      estimate for regional to global carbon cycle studies.

PMID- 29064463
TI  - Personality in the chimpanzees of Gombe National Park.
AB  - Researchers increasingly view animal personality traits as products of natural
      selection. We present data that describe the personalities of 128 eastern
      chimpanzees (Pan troglodytes schweinfurthii) currently living in or who lived
      their lives in the Kasekela and Mitumba communities of Gombe National Park,
      Tanzania. We obtained ratings on 24 items from an established, reliable, well
      validated questionnaire used to study personality in captive chimpanzee
      populations. Ratings were made by former and present Tanzanian field assistants
      who followed individual chimpanzees for years and collected detailed behavioral
      observations. Interrater reliabilities across items ranged from acceptable to
      good, but the personality dimensions they formed were not as interpretable as
      those from captive samples. However, the personality dimensions corresponded to
      ratings of 24 Kasekela chimpanzees on a different questionnaire in 1973 that
      assessed some similar traits. These correlations established the repeatability
      and construct validity of the present ratings, indicating that the present data
      can facilitate historical and prospective studies that will lead to better
      understanding of the evolution of personality in chimpanzees and other primates.

PMID- 29064466
TI  - Experimental formation enthalpies for intermetallic phases and other inorganic
      compounds.
AB  - The standard enthalpy of formation of a compound is the energy associated with
      the reaction to form the compound from its component elements. The standard
      enthalpy of formation is a fundamental thermodynamic property that determines its
      phase stability, which can be coupled with other thermodynamic data to calculate
      phase diagrams. Calorimetry provides the only direct method by which the standard
      enthalpy of formation is experimentally measured. However, the measurement is
      often a time and energy intensive process. We present a dataset of enthalpies of
      formation measured by high-temperature calorimetry. The phases measured in this
      dataset include intermetallic compounds with transition metal and rare-earth
      elements, metal borides, metal carbides, and metallic silicides. These
      measurements were collected from over 50 years of calorimetric experiments. The
      dataset contains 1,276 entries on experimental enthalpy of formation values and
      structural information. Most of the entries are for binary compounds but ternary
      and quaternary compounds are being added as they become available. The dataset
      also contains predictions of enthalpy of formation from first-principles
      calculations for comparison.

PMID- 29064465
TI  - Small non-coding RNA transcriptome of the NCI-60 cell line panel.
AB  - Only 3% of the transcribed human genome is translated into protein, and small non
      coding RNAs from these untranslated regions have demonstrated critical roles in
      transcriptional and translational regulation of proteins. Here, we provide a
      resource that will facilitate cell line selection for gene expression studies
      involving sncRNAs in cancer research. As the most accessible and tractable models
      of tumours, cancer cell lines are widely used to study cancer development and
      progression. The NCI-60 panel of 59 cancer cell lines was curated to provide
      common models for drug screening in 9 tissue types; however, its prominence has
      extended to use in gene regulation, xenograft models, and beyond. Here, we
      present the complete small non-coding RNA (sncRNA) transcriptomes of these 59
      cancer cell lines. Additionally, we examine the abundance and unique sequences of
      annotated microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nuclear RNAs
      (snRNAs), and small nucleolar RNAs (snoRNAs), and reveal novel unannotated
      microRNA sequences.

PMID- 29064467
TI  - Parkinson disease: Caffeine and nicotine do not provide symptomatic relief in
      Parkinson disease.

PMID- 29064468
TI  - Neuromuscular disease: Tadalafil fails to halt the progression of Duchenne
      muscular dystrophy.

PMID- 29064469
TI  - Movement disorders: Patients with spinocerebellar ataxia 38 benefit from DHA
      supplementation.

PMID- 29064470
TI  - Neurometabolic disease: Gene therapy success for cerebral adrenoleukodystrophy.

PMID- 29064471
TI  - Nasopharyngeal metagenomic deep sequencing data, Lancaster, UK, 2014-2015.
AB  - Nasopharyngeal swabs were taken from volunteers attending a general medical
      practice and a general hospital in Lancaster, UK, and at Lancaster University, in
      the winter of 2014-2015. 51 swabs were selected based on high RNA yield and
      allocated to deep sequencing pools as follows: patients with chronic obstructive
      pulmonary disease; asthmatics; adults with no respiratory symptoms; adults with
      feverish respiratory symptoms; adults with respiratory symptoms and presence of
      antibodies against influenza C; paediatric patients with respiratory symptoms (2
      pools); adults with influenza C infection (2 pools), giving a total of 9 pools.
      Illumina sequencing was performed, with data yields per pool in the range of
      345.6 megabases to 14 gigabases after removal of reads aligning to the human
      genome. The data were deposited in the Sequence Read Archive at NCBI, and
      constitute a resource for study of the viral, bacterial and fungal metagenome of
      the human nasopharynx in healthy and diseased states and comparison with other
      metagenomic studies on the human respiratory tract.

PMID- 29064473
TI  - Corrigendum: Diffraction data of core-shell nanoparticles from an X-ray free
      electron laser.
AB  - This corrects the article DOI: 10.1038/sdata.2017.48.

PMID- 29064474
TI  - Long-term metabolic risk for the metabolically healthy overweight/obese
      phenotype.
AB  - BACKGROUND/OBJECTIVES: The clinical relevance of the metabolically healthy
      overweight/obese (MHO) phenotype is controversial and the relationships between
      weight change and the development of cardiometabolic risk factors is unknown.
      Therefore, we aim to: (1) Assess the long-term risk of developing one or more
      components of the metabolic syndrome in MHO adults compared with metabolically
      healthy normal weight (MHNW); (2) Evaluate risk of a composite of death,
      cardiovascular disease (CVD), and risk of developing type 2 diabetes between
      adults defined according to baseline body mass index and metabolic health.
      SUBJECTS/METHODS: Retrospective cohort study of adults 18-65 years of age seen at
      our institution between 1998 and 2000 who lived in Olmsted County. Metabolically
      healthy was defined as the absence of all components of the metabolic syndrome
      (except for waist circumference). Main outcome was the development of metabolic
      risk factors. The secondary outcome was a composite of mortality, CVD and heart
      failure. RESULTS: Of the 18 070 individuals with complete data at baseline, 1805
      (10%) were MHO (mean age 38+/-11 years) and 3047 were MHNW (mean age 35+/-11
      years). After a median follow-up of 15 years, interquartile range 10-17, 80% of
      MHO vs 68% of MHNW developed at least one cardiometabolic risk factor (P<0.001).
      In multivariate analysis, MHO individuals who gained ?10% of their body weight
      were more likely to have developed metabolic complications compared to MHO
      individuals that did not gain weight (P=0.001 for 10-15%, P<0.001 for >15% weight
      gain). The risk for the secondary composite end point was similar between MHO and
      MHNW, number of events 218/1805 vs 217/3048 for MHO and MHNW, respectively,
      (hazard ratio: 1.16, 95% confidence interval: 0.96-1.40). CONCLUSIONS: MHO are
      more likely to develop metabolic complications than MHNW, especially if they gain
      weight.

PMID- 29064472
TI  - Genome-wide association studies of smooth pursuit and antisaccade eye movements
      in psychotic disorders: findings from the B-SNIP study.
AB  - Eye movement deviations, particularly deficits of initial sensorimotor processing
      and sustained pursuit maintenance, and antisaccade inhibition errors, are
      established intermediate phenotypes for psychotic disorders. We here studied eye
      movement measures of 849 participants from the Bipolar-Schizophrenia Network on
      Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective
      disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as
      quantitative phenotypes in relation to genetic data, while controlling for
      genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide
      association studies approach was used including ~4.4 million genotypes (PsychChip
      and 1000 Genomes imputation). Across participants, sensorimotor processing at
      pursuit initiation was significantly associated with a single nucleotide
      polymorphism in IPO8 (12p11.21, P=8 * 10-11), whereas suggestive associations
      with sustained pursuit maintenance were identified with SNPs in SH3GL2 (9p22.2,
      P=3 * 10-8). In participants of predominantly African ancestry, sensorimotor
      processing was also significantly associated with SNPs in PCDH12 (5q31.3, P=1.6 *
      10-10), and suggestive associations were observed with NRSN1 (6p22.3, P=5.4 * 10
      8) and LMO7 (13q22.2, P=7.3x10-8), whereas antisaccade error rate was
      significantly associated with a non-coding region at chromosome 7 (P=6.5 * 10-9).
      Exploratory pathway analyses revealed associations with nervous system
      development and function for 40 top genes with sensorimotor processing and
      pursuit maintenance (P=4.9 * 10-2-9.8 * 10-4). Our findings suggest novel
      patterns of genetic variation relevant for brain systems subserving eye movement
      control known to be impaired in psychotic disorders. They include genes involved
      in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and
      synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal
      degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous
      system development and function.

PMID- 29064475
TI  - Brain substrates of unhealthy versus healthy food choices: influence of
      homeostatic status and body mass index.
AB  - BACKGROUND/OBJECTIVES: Unhealthy dietary choices are a major contributor to
      harmful weight gain and obesity. This study interrogated the brain substrates of
      unhealthy versus healthy food choices in vivo, and evaluated the influence of
      hunger state and body mass index (BMI) on brain activation and connectivity.
      SUBJECTS/METHODS: Thirty adults (BMI: 18-38 kg m-2) performed a food-choice task
      involving preference-based selection between beverage pairs consisting of high
      calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional
      magnetic resonance imaging (fMRI). Selected food stimuli were delivered to
      participants using an MRI-compatible gustometer. fMRI scans were performed both
      after 10-h fasting and when sated. Brain activation and hypothalamic functional
      connectivity were assessed when selecting between unhealthy-healthy beverage
      pairings, relative to unhealthy-unhealthy and healthy-healthy options. Results
      were considered significant at cluster-based family-wise error corrected P<0.05.
      RESULTS: Selecting between unhealthy and healthy foods elicited significant
      activation in the hypothalamus, the medial and dorsolateral prefrontal cortices,
      the anterior insula and the posterior cingulate. Hunger was associated with
      higher activation within the ventromedial and dorsolateral prefrontal cortices,
      as well as lower connectivity between the hypothalamus and both the ventromedial
      prefrontal cortex and dorsal striatum. Critically, people with higher BMI showed
      lower activation of the hypothalamus-regardless of hunger state-and higher
      activation of the ventromedial prefrontal cortex when hungry. CONCLUSIONS: People
      who are overweight and obese have weaker activation of brain regions involved in
      energy regulation and greater activation of reward valuation regions while making
      choices between unhealthy and healthy foods. These results provide evidence for a
      shift towards hedonic-based, and away from energy-based, food selection in
      obesity.

PMID- 29064476
TI  - Perirenal fat is related to carotid intima-media thickness in children.
AB  - BACKGROUND/OBJECTIVES: It is well known that increased abdominal fat is
      associated with cardiovascular (CV) risk. Perirenal fat has been recently
      associated with CV risk in adults. However, studies with children are lacking. We
      investigated the relationship of perirenal fat and other abdominal fat depots
      (including preperitoneal, intra-abdominal and subcutaneous fat) with carotid
      intima-media thickness (cIMT-a surrogate marker of CV risk) in prepubertal
      children, so as to identify novel markers that can be easily assessed and used in
      the early prevention of cardiovascular disease. SUBJECTS/METHODS: Subjects were
      702 asymptomatic prepubertal Caucasian children (418 lean, 142 overweight and 142
      obese) who were recruited in a primary care setting. Ultrasound measurements
      (perirenal, preperitoneal, intra-abdominal and subcutaneous fat and cIMT),
      clinical (body mass index (BMI) and systolic blood pressure) and metabolic
      parameters (insulin resistance (HOMA-IR), high molecular weight (HMW) adiponectin
      and serum lipids) were assessed. RESULTS: Perirenal fat was associated with
      diverse metabolic and CV risk factors in all the studied subjects. However, in
      overweight and obese children, perirenal fat was mostly associated with cIMT
      (P<0.001) and was the only fat depot that showed independent associations with
      cIMT in multivariate analyses (overweight chidren: beta=0.250, P=0.003, r2=12.8%;
      obese children: beta=0.254, P=0.002, r2=15.5%) after adjusting for BMI, gender,
      age and metabolic parameters. Perirenal fat was also the only fat depot that
      showed independent associations with HMW-adiponectin in obese children (beta=
      0.263, P=0.006, r2=22.8%). CONCLUSIONS: Perirenal fat is the main abdominal fat
      depot associated with cIMT, especially in overweight and obese children, and may
      thus represent a helpful parameter for assessing CV risk in the pediatric
      population.

PMID- 29064477
TI  - Earlier BMI rebound and lower pre-rebound BMI as risk of obesity among Japanese
      preschool children.
AB  - OBJECTIVES: Longitudinal growth data of children were analyzed to clarify the
      relationship between the timing of body mass index (BMI) rebound and obesity risk
      in later ages. SUBJECTS/METHODS: Of 54 558 children born between April 2004 and
      March 2005 and longitudinally measured in April and October every year in the
      preschool period, 15 255 children were analyzed wherein no longitudinal
      measurement is missing after 1 year of age. BMI rebound age was determined as the
      age with smallest BMI value across longitudinal individual data after 1 year of
      age. Rebound age was compared between overweight and non-overweight groups. The
      subjects were divided into groups based on the timing of rebound. The sex- and
      age-adjusted mean of the BMI, height and weight s.d. scores for age group, along
      with 6 months weight and height gain, were compared among groups using analysis
      of covariance. RESULTS: Among those who were overweight at 66-71 months of age,
      BMI rebound age obtained at approximately 3 years of age was compared with the
      non-overweight group, whose BMI rebound age was utmost 66 months or later
      (P<0.001). The comparison among BMI age group showed that earlier BMI rebound
      results in larger BMI (P<0.001) and larger weight and height gain after the
      rebound (P<0.001). Among the group with BMI rebound earlier than 30 months of
      age, low BMI was observed (P<0.001). Slight elevation of height and weight gain
      was observed before the BMI rebound among groups with rebound age earlier than 60
      months of age (P<0.001). CONCLUSION: Earlier BMI rebound timing with pre-rebound
      low BMI leads to greater childhood obesity risk; hence, early detection and
      prevention is necessary for such cases.

PMID- 29064478
TI  - DNA methylation in blood from neonatal screening cards and the association with
      BMI and insulin sensitivity in early childhood.
AB  - BACKGROUND/OBJECTIVES: There is increasing evidence that metabolic diseases
      originate in early life, and epigenetic changes have been implicated as key
      drivers of this early life programming. This led to the hypothesis that
      epigenetic marks present at birth may predict an individual's future risk of
      obesity and type 2 diabetes. In this study, we assessed whether epigenetic marks
      in blood of newborn children were associated with body mass index (BMI) and
      insulin sensitivity later in childhood. SUBJECTS/METHODS: DNA methylation was
      measured in neonatal blood spot samples of 438 children using the Illumina
      Infinium 450 k BeadChip. Associations were assessed between DNA methylation at
      birth and BMI z-scores, body fat mass, fasting plasma glucose, insulin and
      homeostatic model assessment of insulin resistance (HOMA-IR) at age 5 years, as
      well as birth weight, maternal BMI and smoking status. RESULTS: No individual
      methylation sites at birth were associated with obesity or insulin sensitivity
      measures at 5 years. DNA methylation in 69 genomic regions at birth was
      associated with BMI z-scores at age 5 years, and in 63 regions with HOMA-IR. The
      methylation changes were generally small (<5%), except for a region near the non
      coding RNA nc886 (VTRNA2-1) where a clear link between methylation status at
      birth and BMI in childhood was observed (P=0.001). Associations were also found
      between DNA methylation, maternal smoking and birth weight. CONCLUSIONS: We
      identified a number of DNA methylation regions at birth that were associated with
      obesity or insulin sensitivity measurements in childhood. These findings support
      the mounting evidence on the role of epigenetics in programming of metabolic
      health. Whether many of these small changes in DNA methylation are causally
      related to the health outcomes, and of clinical relevance, remains to be
      determined, but the nc886 region represents a promising obesity risk marker that
      warrants further investigation.

PMID- 29064479
TI  - Recurrent patterns of microdiversity in a temperate coastal marine environment.
AB  - Temperate coastal marine environments are replete with complex biotic and abiotic
      interactions that are amplified during spring and summer phytoplankton blooms.
      During these events, heterotrophic bacterioplankton respond to successional
      releases of dissolved organic matter as algal cells are lysed. Annual seasonal
      shifts in the community composition of free-living bacterioplankton follow
      broadly predictable patterns, but whether similar communities respond each year
      to bloom disturbance events remains unknown owing to a lack of data sets,
      employing high-frequency sampling over multiple years. We capture the fine-scale
      microdiversity of these events with weekly sampling using a high-resolution
      method to discriminate 16S ribosomal RNA gene amplicons that are >99% identical.
      Furthermore, we used 2 complete years of data to facilitate identification of
      recurrent sub-networks of co-varying microbes. We demonstrate that despite inter
      annual variation in phytoplankton blooms and despite the dynamism of a coastal
      oceanic transition zone, patterns of microdiversity are recurrent during both
      bloom and non-bloom conditions. Sub-networks of co-occurring microbes identified
      reveal that correlation structures between community members appear quite stable
      in a seasonally driven response to oligotrophic and eutrophic conditions.

PMID- 29064480
TI  - Bacterial SBP56 identified as a Cu-dependent methanethiol oxidase widely
      distributed in the biosphere.
AB  - Oxidation of methanethiol (MT) is a significant step in the sulfur cycle. MT is
      an intermediate of metabolism of globally significant organosulfur compounds
      including dimethylsulfoniopropionate (DMSP) and dimethylsulfide (DMS), which have
      key roles in marine carbon and sulfur cycling. In aerobic bacteria, MT is
      degraded by a MT oxidase (MTO). The enzymatic and genetic basis of MT oxidation
      have remained poorly characterized. Here, we identify for the first time the MTO
      enzyme and its encoding gene (mtoX) in the DMS-degrading bacterium Hyphomicrobium
      sp. VS. We show that MTO is a homotetrameric metalloenzyme that requires Cu for
      enzyme activity. MTO is predicted to be a soluble periplasmic enzyme and a member
      of a distinct clade of the Selenium-binding protein (SBP56) family for which no
      function has been reported. Genes orthologous to mtoX exist in many bacteria able
      to degrade DMS, other one-carbon compounds or DMSP, notably in the marine model
      organism Ruegeria pomeroyi DSS-3, a member of the Rhodobacteraceae family that is
      abundant in marine environments. Marker exchange mutagenesis of mtoX disrupted
      the ability of R. pomeroyi to metabolize MT confirming its function in this DMSP
      degrading bacterium. In R. pomeroyi, transcription of mtoX was enhanced by DMSP,
      methylmercaptopropionate and MT. Rates of MT degradation increased after pre
      incubation of the wild-type strain with MT. The detection of mtoX orthologs in
      diverse bacteria, environmental samples and its abundance in a range of
      metagenomic data sets point to this enzyme being widely distributed in the
      environment and having a key role in global sulfur cycling.

PMID- 29064481
TI  - Development of a modeling approach to estimate indoor-to-outdoor sulfur ratios
      and predict indoor PM2.5 and black carbon concentrations for Eastern
      Massachusetts households.
AB  - The effects of indoor air pollution on human health have drawn increasing
      attention among the scientific community as individuals spend most of their time
      indoors. However, indoor air sampling is labor-intensive and costly, which limits
      the ability to study the adverse health effects related to indoor air pollutants.
      To overcome this challenge, many researchers have attempted to predict indoor
      exposures based on outdoor pollutant concentrations, home characteristics, and
      weather parameters. Typically, these models require knowledge of the infiltration
      factor, which indicates the fraction of ambient particles that penetrates
      indoors. For estimating indoor fine particulate matter (PM2.5) exposure, a common
      approach is to use the indoor-to-outdoor sulfur ratio (Sindoor/Soutdoor) as a
      proxy of the infiltration factor. The objective of this study was to develop a
      robust model that estimates Sindoor/Soutdoor for individual households that can
      be incorporated into models to predict indoor PM2.5 and black carbon (BC)
      concentrations. Overall, our model adequately estimated Sindoor/Soutdoor with an
      out-of-sample by home-season R2 of 0.89. Estimated Sindoor/Soutdoor reflected
      behaviors that influence particle infiltration, including window opening, use of
      forced air heating, and air purifier. Sulfur ratio-adjusted models predicted
      indoor PM2.5 and BC with high precision, with out-of-sample R2 values of 0.79 and
      0.76, respectively.

PMID- 29064482
TI  - Development of a total hydrocarbon ordinal job-exposure matrix for workers
      responding to the Deepwater Horizon disaster: The GuLF STUDY.
AB  - The GuLF STUDY is a cohort study investigating the health of workers who
      responded to the Deepwater Horizon oil spill in the Gulf of Mexico in 2010. The
      objective of this effort was to develop an ordinal job-exposure matrix (JEM) of
      airborne total hydrocarbons (THC), dispersants, and particulates to estimate
      study participants' exposures. Information was collected on participants' spill
      related tasks. A JEM of exposure groups (EGs) was developed from tasks and THC
      air measurements taken during and after the spill using relevant exposure
      determinants. THC arithmetic means were developed for the EGs, assigned ordinal
      values, and linked to the participants using determinants from the questionnaire.
      Different approaches were taken for combining exposures across EGs. EGs for
      dispersants and particulates were based on questionnaire responses. Considerable
      differences in THC exposure levels were found among EGs. Based on the maximum THC
      level participants experienced across any job held, ~14% of the subjects were
      identified in the highest exposure category. Approximately 10% of the cohort was
      exposed to dispersants or particulates. Considerable exposure differences were
      found across the various EGs, facilitating investigation of exposure-response
      relationships. The JEM is flexible to allow for different assumptions about
      several possibly relevant exposure metrics.

PMID- 29064483
TI  - Coupling external with internal exposure metrics of trihalomethanes in young
      females from Kuwait and Cyprus.
AB  - The Eastern Mediterranean and the Middle Eastern regions are both understudied in
      terms of possible environmental health risks for their populations. Water
      scarcity and desalination treatment provide the general population of countries
      from these regions (e.g., Kuwait and Cyprus) with unique tap water
      characteristics. This study investigated the association between external (tap
      water and 24 h personal air samples) and internal (urine) THM exposure metrics
      that reflected information about THM-related habits and activities collected
      using questionnaires and time activity diaries. The study population comprised of
      young females residing in either Kuwait (n=13) or Cyprus (n=22). First morning
      urine voids were collected on 2 consecutive days. Urinary creatinine-adjusted
      total THM (TTHM) levels were higher in Kuwait (median (interquartile range): 1044
      (814, 1270) ng/g) than in Cyprus (691 (510, 919) ng/g, P<0.05). Median personal
      air TTHM levels in Kuwait (1.4 (0.7, 1.7) MUg/m3) were higher than those in
      Cyprus (0.9 (0.5, 1.4) MUg/m3), but did not reach statistical significance
      (P=0.17). Median tap water TTHM in Kuwait (6.7 (5.4, 11.6) MUg/l) did not
      correlate with urinary or air THM and they were lower than those in Cyprus (29.5
      (20.1, 48.0) MUg/l; P<0.01). Despite that tap water did not contain chloroform
      (TCM), TCM was detected in both air and urine samples in Kuwait, suggesting other
      TCM exposure sources, such as household cleaning activities. Total duration of
      activities and mopping were significantly correlated with air and urine THM in
      Kuwait, as reported in the time activity diary. Personal air and urine exposure
      metrics were correlated in Kuwait (TTHM rho=0.62, P<0.05), but not in Cyprus
      (TTHM rho=-0.32, P>0.05). Time-activity diaries and urinary THM seemed to be
      useful measures of THM exposures in Kuwait. Coupling both external with internal
      exposure metrics could find use in population health studies towards further
      refining the association between environmental exposures and health outcomes.

PMID- 29064484
TI  - JAM-A as a prognostic factor and new therapeutic target in multiple myeloma.
AB  - Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized
      as a major mechanism of MM cell survival and the development of drug resistance.
      Here we addressed the hypothesis that the protein junctional adhesion molecule-A
      (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated
      JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and
      biopsies at different disease stages. Elevated JAM-A levels in patient-derived
      plasma cells were correlated with poor prognosis. Moreover, circulating soluble
      JAM-A (sJAM-A) levels were significantly increased in MM patients as compared
      with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony
      formation, chemotaxis, proliferation and viability. In vivo treatment with an
      anti-JAM-A monoclonal antibody (alphaJAM-A moAb) impaired tumor progression in a
      murine xenograft MM model. These results demonstrate that therapeutic targeting
      of JAM-A has the potential to prevent MM progression, and lead us to propose JAM
      A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical
      stratification.

PMID- 29064487
TI  - Nihonium the obscure.

PMID- 29064486
TI  - Direct, enantioselective alpha-alkylation of aldehydes using simple olefins.
AB  - Although the alpha-alkylation of ketones has already been established, the
      analogous reaction using aldehyde substrates has proven surprisingly elusive.
      Despite the structural similarities between the two classes of compounds, the
      sensitivity and unique reactivity of the aldehyde functionality has typically
      required activated substrates or specialized additives. Here, we show that the
      synergistic merger of three catalytic processes-photoredox, enamine and hydrogen
      atom transfer (HAT) catalysis-enables an enantioselective alpha-aldehyde
      alkylation reaction that employs simple olefins as coupling partners. Chiral
      imidazolidinones or prolinols, in combination with a thiophenol, iridium
      photoredox catalyst and visible light, have been successfully used in a triple
      catalytic process that is temporally sequenced to deliver a new hydrogen and
      electron-borrowing mechanism. This multicatalytic process enables both intra- and
      intermolecular aldehyde alpha-methylene coupling with olefins to construct both
      cyclic and acyclic products, respectively. With respect to atom and step-economy
      ideals, this stereoselective process allows the production of high-value
      molecules from feedstock chemicals in one step while consuming only photons.

PMID- 29064485
TI  - Differential impact of drugs on the outcome of ETV6-RUNX1 positive childhood B
      cell precursor acute lymphoblastic leukaemia: results of the EORTC CLG 58881 and
      58951 trials.

PMID- 29064488
TI  - Local epigenetic reprogramming induced by G-quadruplex ligands.
AB  - DNA and histone modifications regulate transcriptional activity and thus
      represent valuable targets to reprogram the activity of genes. Current epigenetic
      therapies target the machinery that regulates these modifications, leading to
      global transcriptional reprogramming with the potential for extensive undesired
      effects. Epigenetic information can also be modified as a consequence of
      disrupting processive DNA replication. Here, we demonstrate that impeding
      replication by small-molecule-mediated stabilization of G-quadruplex nucleic acid
      secondary structures triggers local epigenetic plasticity. We report the use of
      the BU-1 locus of chicken DT40 cells to screen for small molecules able to induce
      G-quadruplex-dependent transcriptional reprogramming. Further characterization of
      the top hit compound revealed its ability to induce a dose-dependent inactivation
      of BU-1 expression in two steps: the loss of H3K4me3 and then subsequent DNA
      cytosine methylation, changes that were heritable across cell divisions even
      after the compound was removed. Targeting DNA secondary structures thus
      represents a potentially new approach for locus-specific epigenetic
      reprogramming.

PMID- 29064489
TI  - Engineering nucleic acid structures for programmable molecular circuitry and
      intracellular biocomputation.
AB  - Nucleic acids have attracted widespread attention due to the simplicity with
      which they can be designed to form discrete structures and programmed to perform
      specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology
      offer numerous opportunities for in-cell and in-vivo applications, and the
      technology holds great promise to advance the growing field of synthetic biology.
      Many elegant examples have revealed the potential in integrating nucleic acid
      nanostructures in cells and in vivo where they can perform important
      physiological functions. In this Review, we summarize the current abilities of
      DNA/RNA nanotechnology to realize applications in live cells and then discuss the
      key problems that must be solved to fully exploit the useful properties of
      nanostructures. Finally, we provide viewpoints on how to integrate the tools
      provided by DNA/RNA nanotechnology and related new technologies to construct
      nucleic acid nanostructure-based molecular circuitry for synthetic biology.

PMID- 29064491
TI  - Gas-phase chemical kinetics: Three is the magic number.

PMID- 29064492
TI  - Assembly of a biocompatible triazole-linked gene by one-pot click-DNA ligation.
AB  - The chemical synthesis of oligonucleotides and their enzyme-mediated assembly
      into genes and genomes has significantly advanced multiple scientific
      disciplines. However, these approaches are not without their shortcomings;
      enzymatic amplification and ligation of oligonucleotides into genes and genomes
      makes automation challenging, and site-specific incorporation of epigenetic
      information and/or modified bases into large constructs is not feasible. Here we
      present a fully chemical one-pot method for the assembly of oligonucleotides into
      a gene by click-DNA ligation. We synthesize the 335 base-pair gene that encodes
      the green fluorescent protein iLOV from ten functionalized oligonucleotides that
      contain 5'-azide and 3'-alkyne units. The resulting click-linked iLOV gene
      contains eight triazoles at the sites of chemical ligation, and yet is fully
      biocompatible; it is replicated by DNA polymerases in vitro and encodes a
      functional iLOV protein in Escherichia coli. We demonstrate the power and
      potential of our one-pot gene-assembly method by preparing an epigenetically
      modified variant of the iLOV gene.

PMID- 29064490
TI  - Fluorescent nucleobases as tools for studying DNA and RNA.
AB  - Understanding the diversity of dynamic structures and functions of DNA and RNA in
      biology requires tools that can selectively and intimately probe these
      biomolecules. Synthetic fluorescent nucleobases that can be incorporated into
      nucleic acids alongside their natural counterparts have emerged as a powerful
      class of molecular reporters of location and environment. They are enabling new
      basic insights into DNA and RNA, and are facilitating a broad range of new
      technologies with chemical, biological and biomedical applications. In this
      Review, we will present a brief history of the development of fluorescent
      nucleobases and explore their utility as tools for addressing questions in
      biophysics, biochemistry and biology of nucleic acids. We provide chemical
      insights into the two main classes of these compounds: canonical and non
      canonical nucleobases. A point-by-point discussion of the advantages and
      disadvantages of both types of fluorescent nucleobases is made, along with a
      perspective into the future challenges and outlook for this burgeoning field.

PMID- 29064493
TI  - A triaxial supramolecular weave.
AB  - Despite recent advances in the synthesis of increasingly complex topologies at
      the molecular level, nano- and microscopic weaves have remained difficult to
      achieve. Only a few diaxial molecular weaves exist-these were achieved by
      templation with metals. Here, we present an extended triaxial supramolecular
      weave that consists of self-assembled organic threads. Each thread is formed by
      the self-assembly of a building block comprising a rigid oligoproline segment
      with two perylene-monoimide chromophores spaced at 18 A. Upon pi stacking of the
      chromophores, threads form that feature alternating up- and down-facing voids at
      regular distances. These voids accommodate incoming building blocks and establish
      crossing points through CH-pi interactions on further assembly of the threads
      into a triaxial woven superstructure. The resulting micrometre-scale
      supramolecular weave proved to be more robust than non-woven self-assemblies of
      the same building block. The uniform hexagonal pores of the interwoven network
      were able to host iridium nanoparticles, which may be of interest for practical
      applications.

PMID- 29064494
TI  - Synthesis facilitates an understanding of the structural basis for translation
      inhibition by the lissoclimides.
AB  - The lissoclimides are unusual succinimide-containing labdane diterpenoids that
      were reported to be potent cytotoxins. Our short semisynthesis and analogue
      oriented synthesis approaches provide a series of lissoclimide natural products
      and analogues that expand the structure-activity relationships (SARs) in this
      family. The semisynthesis approach yielded significant quantities of
      chlorolissoclimide (CL) to permit an evaluation against the National Cancer
      Institute's 60-cell line panel and allowed us to obtain an X-ray co-crystal
      structure of the synthetic secondary metabolite with the eukaryotic 80S ribosome.
      Although it shares a binding site with other imide-based natural product
      translation inhibitors, CL engages in a particularly interesting and novel face
      on halogen-pi interaction between the ligand's alkyl chloride and a guanine
      residue. Our analogue-oriented synthesis provides many more lissoclimide
      compounds, which were tested against aggressive human cancer cell lines and for
      protein synthesis inhibitory activity. Finally, computational modelling was used
      to explain the SARs of certain key compounds and set the stage for the structure
      guided design of better translation inhibitors.

PMID- 29064495
TI  - Bifluoride-catalysed sulfur(VI) fluoride exchange reaction for the synthesis of
      polysulfates and polysulfonates.
AB  - Polysulfates and polysulfonates possess exceptional mechanical properties making
      them potentially valuable engineering polymers. However, they have been little
      explored due to a lack of reliable synthetic access. Here we report bifluoride
      salts (Q+[FHF]-, where Q+ represents a wide range of cations) as powerful
      catalysts for the sulfur(VI) fluoride exchange (SuFEx) reaction between aryl
      silyl ethers and aryl fluorosulfates (or alkyl sulfonyl fluorides). The
      bifluoride salts are significantly more active in catalysing the SuFEx reaction
      compared to organosuperbases, therefore enabling much lower catalyst-loading
      (down to 0.05 mol%). Using this chemistry, we are able to prepare polysulfates
      and polysulfonates with high molecular weight, narrow polydispersity and
      excellent functional group tolerance. The process is practical with regard to the
      reduced cost of catalyst, polymer purification and by-product recycling. We have
      also observed that the process is not sensitive to scale-up, which is essential
      for its future translation from laboratory research to industrial applications.

PMID- 29064496
TI  - CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via
      shuttle catalysis.
AB  - The synthesis of carboxylic acid derivatives from unsaturated hydrocarbons is an
      important process for the preparation of polymers, pharmaceuticals, cosmetics and
      agrochemicals. Despite its industrial relevance, the traditional Reppe-type
      carbonylation reaction using pressurized CO is of limited applicability to
      laboratory-scale synthesis because of: (1) the safety hazards associated with the
      use of CO, (2) the need for special equipment to handle pressurized gas, (3) the
      low reactivity of several relevant nucleophiles and (4) the necessity to employ
      different, often tailor-made, catalytic systems for each nucleophile. Herein we
      demonstrate that a shuttle-catalysis approach enables a CO- and HCl-free transfer
      process between an inexpensive reagent, butyryl chloride, and a wide range of
      unsaturated substrates to access the corresponding acid chlorides in good yields.
      This new transformation provides access to a broad range of carbonyl-containing
      products through the in situ transformation of the reactive acid chloride
      intermediate. In a broader context, this work demonstrates that isodesmic shuttle
      catalysis reactions can unlock elusive catalytic reactions.

PMID- 29064497
TI  - The changing culture of chemistry.

PMID- 29064498
TI  - Ephemeral collision complexes mediate chemically termolecular transformations
      that affect system chemistry.
AB  - Termolecular association reactions involve ephemeral collision complexes-formed
      from the collision of two molecules-that collide with a third and chemically
      inert 'bath gas' molecule that simply transfers energy to/from the complex. These
      collision complexes are generally not thought to react chemically on collision
      with a third molecule in the gas-phase systems of combustion and planetary
      atmospheres. Such 'chemically termolecular' reactions, in which all three
      molecules are involved in bond making and/or breaking, were hypothesized long ago
      in studies establishing radical chain branching mechanisms, but were later
      concluded to be unimportant. Here, with data from ab initio master equation and
      kinetic-transport simulations, we reveal that reactions of H + O2 collision
      complexes with other radicals constitute major kinetic pathways under common
      combustion situations. These reactions are also found to influence flame
      propagation speeds, a common measure of global reactivity. Analogous chemically
      termolecular reactions mediated by ephemeral collision complexes are probably of
      significance in various combustion and planetary environments.

PMID- 29064499
TI  - Thermally bisignate supramolecular polymerization.
AB  - One of the enticing characteristics of supramolecular polymers is their
      thermodynamic reversibility, which is attractive, in particular, for stimuli
      responsive applications. These polymers usually disassemble upon heating, but
      here we report a supramolecular polymerization that occurs upon heating as well
      as cooling. This behaviour arises from the use of a metalloporphyrin-based
      tailored monomer bearing eight amide-containing side chains, which assembles into
      a highly thermostable one-dimensional polymer through pi-stacking and multivalent
      hydrogen-bonding interactions, and a scavenger, 1-hexanol, in a dodecane-based
      solvent. At around 50  degrees C, the scavenger locks the monomer into a non
      polymerizable form through competing hydrogen bonding. On cooling, the scavenger
      preferentially self-aggregates, unlocking the monomer for polymerization. Heating
      also results in unlocking the monomer for polymerization, by disrupting the
      dipole and hydrogen-bonding interactions with the scavenger. Analogous to 'upper
      and lower critical solution temperature phenomena' for covalently bonded
      polymers, such a thermally bisignate feature may lead to supramolecular polymers
      with tailored complex thermoresponsive properties.

PMID- 29064501
TI  - Directing the path of light-induced electron transfer at a molecular fork using
      vibrational excitation.
AB  - Ultrafast electron transfer in condensed-phase molecular systems is often
      strongly coupled to intramolecular vibrations that can promote, suppress and
      direct electronic processes. Recent experiments exploring this phenomenon proved
      that light-induced electron transfer can be strongly modulated by vibrational
      excitation, suggesting a new avenue for active control over molecular function.
      Here, we achieve the first example of such explicit vibrational control through
      judicious design of a Pt(II)-acetylide charge-transfer donor-bridge-acceptor
      bridge-donor 'fork' system: asymmetric 13C isotopic labelling of one of the two 
      C=C- bridges makes the two parallel and otherwise identical donor->acceptor
      electron-transfer pathways structurally distinct, enabling independent
      vibrational perturbation of either. Applying an ultrafast UVpump(excitation)
      IRpump(perturbation)-IRprobe(monitoring) pulse sequence, we show that the pathway
      that is vibrationally perturbed during UV-induced electron transfer is
      dramatically slowed down compared to its unperturbed counterpart. One can thus
      choose the dominant electron transfer pathway. The findings deliver a new
      opportunity for precise perturbative control of electronic energy propagation in
      molecular devices.

PMID- 29064500
TI  - A new and selective cycle for dehydrogenation of linear and cyclic alkanes under
      mild conditions using a base metal.
AB  - Selectively converting linear alkanes to alpha-olefins under mild conditions is a
      highly desirable transformation given the abundance of alkanes as well as the use
      of olefins as building blocks in the chemical community. Until now, this reaction
      has been primarily the remit of noble-metal catalysts, despite extensive work
      showing that base-metal alkylidenes can mediate the reaction in a stoichiometric
      fashion. Here, we show how the presence of a hydrogen acceptor, such as the
      phosphorus ylide, when combined with the alkylidene complex (PNP)Ti=CHtBu(CH3)
      (PNP=N[2-P(CHMe2)2-4-methylphenyl]2-), catalyses the dehydrogenation of
      cycloalkanes to cyclic alkenes, and linear alkanes with chain lengths of C4 to C8
      to terminal olefins under mild conditions. This Article represents the first
      example of a homogeneous and selective alkane dehydrogenation reaction using a
      base-metal titanium catalyst. We also propose a unique mechanism for the transfer
      dehydrogenation of hydrocarbons to olefins and discuss a complete cycle based on
      a combined experimental and computational study.

PMID- 29064503
TI  - Epigenetics: Making your mark on DNA.

PMID- 29064504
TI  - Self-assembly: Supramolecular basketry.

PMID- 29064502
TI  - Phase behaviour of disordered proteins underlying low density and high
      permeability of liquid organelles.
AB  - Many intracellular membraneless organelles form via phase separation of
      intrinsically disordered proteins (IDPs) or regions (IDRs). These include the
      Caenorhabditis elegans protein LAF-1, which forms P granule-like droplets in
      vitro. However, the role of protein disorder in phase separation and the
      macromolecular organization within droplets remain elusive. Here, we utilize a
      novel technique, ultrafast-scanning fluorescence correlation spectroscopy, to
      measure the molecular interactions and full coexistence curves (binodals), which
      quantify the protein concentration within LAF-1 droplets. The binodals of LAF-1
      and its IDR display a number of unusual features, including 'high concentration'
      binodal arms that correspond to remarkably dilute droplets. We find that LAF-1
      and other in vitro and intracellular droplets are characterized by an effective
      mesh size of ~3-8 nm, which determines the size scale at which droplet properties
      impact molecular diffusion and permeability. These findings reveal how specific
      IDPs can phase separate to form permeable, low-density (semi-dilute) liquids,
      whose structural features are likely to strongly impact biological function.

PMID- 29064505
TI  - A halogen-bonding-catalyzed Michael addition reaction.
AB  - Only a few studies on the use of halogen bonding in catalysis have been published
      so far. Herein, (benz)imidazolium-based halogen bond donors are used as catalysts
      in a Michael addition reaction. The most potent catalyst, a rigid atropisomer
      featuring two iodobenzimidazolium moieties, provided a rate acceleration versus a
      reference compound of ca. 50.

PMID- 29064509
TI  - Patient-driven N-of-1 in Parkinson's Disease. Lessons Learned from a Placebo
      controlled Study of the Effect of Nicotine on Dyskinesia.
AB  - BACKGROUND: New insights and knowledge in biomedical science often come from
      observation and experimentation. Methods traditionally used include self
      experimentation, case reports, randomised controlled trials, and N-of-1 studies.
      Technological advances have lead to an increasing number of individuals and
      patients engaging in self-tracking. We use the term patient-driven N-of-1 for
      self-tracking performed with the explicit intention to disseminate the results by
      academic publishing. OBJECTIVES: The aim of the study was to: 1) explore the
      potential role for patient-driven N-of-1 studies as a tool for improving self
      management in Parkinson's disease (PD) using the example of managing levodopa
      induced dyskinesia (LID) with nicotine, and 2) based on this example; identify
      some specific challenges of patient-driven N-of-1 studies. METHODS: We used a
      placebo controlled patient-driven N-of-1 study with nicotine administered via e
      cigarette to treat LID. The first author initiated and conducted the experiment
      on herself and noted her observations. The evaluations of the potential of N-of-1
      for improving self-management of PD as well as the effects of nicotine on
      dyskinesia were based on the perception of the subject. During the planning and
      undertaking of the experiment, notes were made to identify challenges specific to
      patient-driven N-of-1 studies. RESULTS: The subject was able to distinguish a
      decrease of her LID from nicotine but no effect from placebo. The main challenges
      of patient-driven N-of-1 studies were identified to be associated with planning
      of the study, recruiting a suitable research team, making sure the data
      collection is optimal, analysis of data, and publication of results. CONCLUSIONS:
      Our study indicates that nicotine administered via e-cigarette may have an effect
      on levodopa-induced dyskinesia in individual patients with PD. The main
      contribution is however highlighting the work done by patients on a daily basis
      for understanding their conditions and conducting self-tracking experiments. More
      work is needed to further develop methods around patient-driven N-of-1 studies
      for PD.

PMID- 29064510
TI  - Biomolecular computers with multiple restriction enzymes.
AB  - The development of conventional, silicon-based computers has several limitations,
      including some related to the Heisenberg uncertainty principle and the von
      Neumann "bottleneck". Biomolecular computers based on DNA and proteins are
      largely free of these disadvantages and, along with quantum computers, are
      reasonable alternatives to their conventional counterparts in some applications.
      The idea of a DNA computer proposed by Ehud Shapiro's group at the Weizmann
      Institute of Science was developed using one restriction enzyme as hardware and
      DNA fragments (the transition molecules) as software and input/output signals.
      This computer represented a two-state two-symbol finite automaton that was
      subsequently extended by using two restriction enzymes. In this paper, we propose
      the idea of a multistate biomolecular computer with multiple commercially
      available restriction enzymes as hardware. Additionally, an algorithmic method
      for the construction of transition molecules in the DNA computer based on the use
      of multiple restriction enzymes is presented. We use this method to construct
      multistate, biomolecular, nondeterministic finite automata with four commercially
      available restriction enzymes as hardware. We also describe an experimental
      applicaton of this theoretical model to a biomolecular finite automaton made of
      four endonucleases.

PMID- 29064511
TI  - Mapping QTLs for drought tolerance in a SEA 5 x AND 277 common bean cross with
      SSRs and SNP markers.
AB  - The common bean is characterized by high sensitivity to drought and low
      productivity. Breeding for drought resistance in this species involves genes of
      different genetic groups. In this work, we used a SEA 5 x AND 277 cross to map
      quantitative trait loci associated with drought tolerance in order to assess the
      factors that determine the magnitude of drought response in common beans. A total
      of 438 polymorphic markers were used to genotype the F8 mapping population.
      Phenotyping was done in two greenhouses, one used to simulate drought and the
      other to simulate irrigated conditions. Fourteen traits associated with drought
      tolerance were measured to identify the quantitative trait loci (QTLs). The map
      was constructed with 331 markers that covered all 11 chromosomes and had a total
      length of 1515 cM. Twenty-two QTLs were discovered for chlorophyll, leaf and stem
      fresh biomass, leaf biomass dry weight, leaf temperature, number of pods per
      plant, number of seeds per plant, seed weight, days to flowering, dry pod weight
      and total yield under well-watered and drought (stress) conditions. All the QTLs
      detected under drought conditions showed positive effects of the SEA 5 allele.
      This study provides a better understanding of the genetic inheritance of drought
      tolerance in common bean.

PMID- 29064512
TI  - Adiponectin promoter polymorphisms are predictors of lipid profile improvement
      after bariatric surgery.
AB  - Our aim was to investigate if single nucleotide polymorphisms (SNPs) located in
      the 5' regions of leptin (LEP, -2548 G > A, rs7799039), resistin (RETN, -420 C >
      G, rs1862513) and adiponectin (ADIPOQ, -11391 G > A, rs17300539 and -11377 C > G,
      rs266729) genes were related to changes in body mass index (BMI) and metabolic
      variables after bariatric surgery in 60 extremely obese individuals. At baseline,
      ADIPOQ -11391 A-allele carriers showed higher plasma adiponectin and lower total
      cholesterol levels when compared to G/G homozygotes. Approximately 32 months post
      surgery, a mean reduction of 35% in BMI and an important improvement in metabolic
      profiles were observed. In addition, for the ADIPOQ -11377 polymorphism, a higher
      decrease in lipid profile was associated to the C/C genotype. Moreover,
      individuals bearing the A-C haplotype for the two ADIPOQ SNPs were more prone to
      show a reduction in low-density lipoprotein levels after bariatric surgery (
      43.0% A-C carriers vs. -18.1% G-G carriers, p = 0.019). We did not find any
      association of leptin and resistin SNPs with the clinical parameters analyzed. In
      summary, our results indicate that the A-C haplotype is a predictor of better
      lipid profile post-surgery and the studied SNPs in ADIPOQ gene are associated to
      changes in metabolic variables in obese individuals.

PMID- 29064513
TI  - The complete mitochondrial genome of Engyodontium album and comparative analyses
      with Ascomycota mitogenomes.
AB  - Engyodontium album is a widespread pathogen that causes different kinds of
      dermatoses and respiratory tract diseases in humans and animals. In spite of its
      perniciousness, the basic genetic and molecular background of this species
      remains poorly understood. In this study, the mitochondrial genome sequence of E.
      album was determined using a high-throughput sequencing platform. The circular
      mitogenome was found to be 28,081 nucleotides in length and comprised of 17
      protein-coding genes, 24 tRNA genes, and 2 rRNA genes. The nucleotide composition
      of the genome was A+T-biased (74.13%). Group-II introns were found in the nad1,
      nad5, and cob genes. The most frequently used codon of protein-coding genes was
      UAU. Isoleucine was identified as the most common amino acid, while proline was
      the least common amino acid in protein-coding genes. The gene-arrangement order
      is nearly the same when compared with other Ascomycota mitogenomes. Phylogenetic
      relationships based on the shared protein-coding genes revealed that E. album is
      closely related to the Cordycipitaceae family, with a high-confidence support
      value (100%). The availability of the mitogenome of E. album will shed light on
      the molecular systematic and genetic differentiation of this species.

PMID- 29064515
TI  - ?
AB  - Patient care always starts with an encounter Being a doctor is essentially a
      moral enterprise and all kinds of care begin with the encounter with the patient.
      This encounter occurs at the intersection of the patient's need for assistance
      and the doctor's professional knowledge. The meeting can be characterised by
      paternalism, autonomy or participation. It is important to regard the patient as
      a person and explore his or her perceptions, apprehensions and expectations early
      in the meeting. All decisions in medicine rely on both facts and values. It is,
      therefore, important that both the doctor's and the patient's values and
      preferences are out in the open. The medical encounter is always asymmetrical,
      which necessitates that the power perspective be acknowledged.

PMID- 29064514
TI  - Comparative transcriptome profile of the leaf elongation zone of wild barley
      (Hordeum spontaneum) eibi1 mutant and its isogenic wild type.
AB  - The naturally occurring wild barley mutant eibi1/hvabcg31 suffers from severe
      water loss due to the permeable leaf cuticle. Eibi1/HvABCG31 encodes a full ATP
      binding cassette (ABC) transporter, HvABCG31, playing a role in cutin deposition
      in the elongation zone of growing barley leaves. The eibi1 allele has pleiotropic
      effects on the appearance of leaves, plant stature, fertility, spike and grain
      size, and rate of germination. Comparative transcriptome profile of the leaf
      elongation zone of the eibi1 mutant as well as its isogenic wild type showed that
      various pathogenesis-related genes were up-regulated in the eibi1 mutant. The
      known cuticle-related genes that we analyzed did not show significant expression
      difference between the mutant and wild type. These results suggest that the
      pleiotropic effects may be a compensatory consequence of the activation of
      defense genes in the eibi1 mutation. Furthermore, we were able to find the
      mutation of the eibi1/hvabcg31 allele by comparing transcript sequences, which
      indicated that the RNA-Seq is useful not only for researches on general molecular
      mechanism but also for the identification of possible mutant genes.

PMID- 29064516
TI  - ?

PMID- 29064517
TI  - ?
AB  - The aim of this article is to elucidate the traditional ward round from an
      historical, ethical and legal perspective. On the traditional ward round in
      hospitals, a senior clinician leads a group of other clinicians and health
      professionals on a walking tour through the ward to visit the patients for whom
      they are responsible at bedside. It is a long-lived tradition or routine, which
      has been substantially resistant to change. We recommend that work designed to
      improve the ward round should begin from values or ethical principles, such as
      respecting the patient's integrity and right to participate in decision-making.
      Moreover, the focal point should be creating opportunities for "the good meeting"
      and patient narratives. A team-based, person-centred ward round has been
      implemented in some hospitals in Sweden. The patient meets the ward team in a
      separate room to discuss the plan of care together. We argue that it is no longer
      possible to defend the traditional way of walking rounds, either ethically or
      legally.

PMID- 29064518
TI  - ?
AB  - Medical simulation training - an overview of the evidence Medical simulation
      training has become an important model for training of technical and non
      technical clinical skills, aiming at preventing avoidable mistakes. The evidence
      for effects of simulation training is increasing, and several systematic reviews
      on the effect of medical simulation training have been published. This article
      summarizes the evidence for medical simulation training based on systematic
      reviews of medical simulation published in the last three years. There is a
      consistent finding in all systematic reviews that simulation training has a
      positive effect on learning and skills transfer, and small positive effects on
      patient-related outcomes. However, there is considerable uncertainty about the
      strength of evidence of this research, and all systematic reviews reported
      serious weaknesses in research methods of the included studies. We hope that the
      newly published guidelines for study design and reporting of medical simulation
      research can help create a stronger evidence base.

PMID- 29064519
TI  - ?

PMID- 29064521
TI  - ?

PMID- 29064520
TI  - ?

PMID- 29064522
TI  - ?

PMID- 29064523
TI  - ?

PMID- 29064524
TI  - ?

PMID- 29064525
TI  - ?

PMID- 29064526
TI  - ?

PMID- 29064527
TI  - ?

PMID- 29064528
TI  - ?

PMID- 29064529
TI  - ?

PMID- 29064530
TI  - ?
AB  - Knot on the epidural catheter, a rare complication: a case report A 30-year 1
      grava woman received an epidural for labor pain. Insertion was uncomplicated and
      she had an effective analgesia. The epidural was successfully converted to
      epidural anaesthesia for Caesarean section. The epidural was removed 24 hours
      thereafter. The mother was lying and trying to curve the back during removal. It
      was initially easy to pull but after some centimeters it became difficult. The
      mother was asked to curve further and pulling continued. The catheter came out
      with some constraints with a knot on the tip. The mother had no pain during
      traction. The subsequent course was uneventful. A knot on the epidural catheter
      is a rare complication to epidural analgesia/anaesthesia. There are several
      reviews giving advice how to avoid its occurrence and how to act if the catheter
      cannot be easily removed. It is advised to limit the length of catheter inserted
      into the epidural space; no more than 4-5 cm. If the catheter is not easily
      removed; "gentle and steady traction" is recommended with the patient initially
      in a position as similar as possible to the one during insertion. If it is still
      not possible to remove, an X-ray or MRI is suggested to confirm that there isn't
      any nerve involvement, followed by pulling firmly again until the catheter comes
      out or breaks. A broken catheter should "in general" be left in place unless
      symptoms occur.

PMID- 29064531
TI  - ?

PMID- 29064532
TI  - A review of the application of reinforced hydrogels and silk as biomaterials for
      intervertebral disc repair.
AB  - The degeneration of the intervertebral disc (IVD) within the spinal column
      represents a major pain source for many patients. Biological restoration or
      repair of the IVD using "compressive-force-resistant" and at the same time
      "cytocompatible" materials would be desirable over current purely mechanical
      solutions, such as spinal fusion or IVD implants. This review provides an
      overview of recent research on the repair of the inner (nucleus pulposus = NP)
      and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have
      addressed NP repair using hydrogel-like materials. However, only a few studies
      have so far focused on AF repair. As the AF possesses an extremely low self
      healing capacity and special attention to shear-force resistance is essential,
      special repair designs are required. In our review, we stated the challenges in
      IVD repair and highlighted the use of composite materials such as silk
      biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the
      origin of silk and its many in tissue engineering. Furthermore, techniques such
      as electrospinning and 3D printing technologies allow the fabrication of
      versatile and functionalised 3D scaffolds. We summarised the research that has
      been conducted in the field of regenerative medicine over the recent years, with
      a special focus on the potential application and the potential of combining silk
      and reinforced - and thus mechanically tailored - hydrogels for IVD repair.

PMID- 29064533
TI  - In vitro effects of particulate bone substitute materials on the resorption
      activity of human osteoclasts.
AB  - Much research has been done on bone cells, but only a few studies deal with
      biomaterial-induced effects on human osteoclasts, which may take on an important
      role in the successful regeneration of bone. In order to highlight such effects,
      human peripheral blood mononuclear cells (PBMCs) were extracted from venous
      blood, differentiated to osteoclasts and then cultured in, the presence of five
      particulate hydroxyapatite (HA)/beta-tricalcium phosphate (TCP) biomaterials, on
      bovine bone slices and glass cover slips. The biomaterials, AlgOSS 50/50 (50 %
      HA/50 % TCP), AlgOSS 20/80 (20 % HA/80 % TCP), Algipore (98 % HA), Cerasorb (100
      % TCP) and Bio-Oss (100 % HA) were chosen to assess their influence on cell
      morphology and numbers. Light microscopic evaluation was performed during ongoing
      cell culture. After 21 d of cultivation, the biomaterial-induced effects on
      osteoclastic resorption of the bone slices were evaluated by scanning electron
      microscopy (SEM). Osteoclast-like cells were identified by TRAP staining. All
      five biomaterials showed larger area fractions of resorbed bone than the control
      (5.6 +/- 6.8 %), as measured on SEM images. The purely hydroxyapatite-based
      Algipore (9.8 +/- 9.7 %) and Bio-Oss (7.9 +/- 8.8 %) showed significantly
      elevated area fraction rates (p <= 0.05) of bone resorption. Light microscope
      evaluation revealed a significant, but inhibiting effect of Cerasorb (p = 0.05).
      These data indicated that introducing of small biomaterial hydroxyapatite
      particles may have improved the performance of bone substitute materials.

PMID- 29064534
TI  - Benefits of laboratory personalized antiplatelet therapy in patients undergoing
      percutaneous coronary intervention: A meta-analysis of randomized controlled
      trials.
AB  - BACKGROUND: The preventive effects of laboratory personalized antiplatelet
      therapy (PAPT) strategy in-cluding genetic detection and platelet function
      testing (PFT) on major adverse cardiac events (MACEs) and bleeding events in
      coronary artery disease (CAD) patients undergoing stenting has been extensively
      studied. Despite that, no clear conclusion can be drawn. In this study, a meta
      analysis was performed to explore a more precise estimation of the benefits of
      laboratory PAPT. METHODS: Randomized controlled trials were identified by the use
      of search databases such as PubMed, Embase, and Cochrane Controlled Trials
      Register up to May 2017, and the estimates were pooled. RESULTS: Fourteen studies
      including 9497 patients met the inclusion criteria. The laboratory PAPT reduced
      MACEs risk (risk ratio [RR] 0.58, 95% confidence interval [CI] 0.42-0.80, p =
      0.001), stent thrombosis (RR 0.60, 95% CI 0.41-0.87, p = 0.008) and myocardial
      infarctions (RR 0.43, 95% CI 0.21-0.88, p = 0.02) compared to the non-PAPT group.
      No statistically significant difference was observed between the two groups
      regarding cardiovascular death (RR 0.77, 95% CI 0.51-1.16, p = 0.21), bleeding
      events (RR 0.96, 95% CI 0.81-1.13, p = 0.59) and ischemic stroke (RR 0.81; 95% CI
      0.39-1.66, p = 0.57). The preventive effect on MACEs was more significant in
      patients with high on-treatment platelet reactivity (RR 0.46; 95% CI 0.27-0.80, p
      = 0.006). CONCLUSIONS: Coronary artery disease patients after stenting could
      obtain benefits from laboratory PAPT. (Cardiol J 2018; 25, 1: 128-141).

PMID- 29064535
TI  - Diagnostic performance of microRNA-133a in acute myocardial infarction: A meta
      analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the diagnostic performance of
      microRNA-133a in the diagnosis of acute myocardial infarction (AMI). METHODS:
      Major databases including PubMed, Embase and the Cochrane Library were searched
      for case-controlled studies comparing AMI and non-AMI patients. The outcome was
      evaluated by the relative expression of microRNA-133a in plasma or serum. The
      Mantel-Haenszel odds ratio (OR) was calculated using a fixed-effects model meta
      analysis for the outcome. The primary outcomes of interest were pooled
      sensitivity, specificity and diagnostic accuracy of microRNA-133a for AMI.
      RESULTS: Out of 137 identified related articles, 10 were found to conform with
      the inclusion and ex-clusion criteria of the study. The 10 case-controlled
      studies contained complete data for 1,074 patients (with no restrictions of race,
      age or sex), and a database containing 137 patients from the registry of each
      study. In addition to low heterogeneity, a statistically significant increase was
      found in overall microRNA-133a expression between AMI vs. non-AMI; the pooled OR
      was 22.84 (95% confidence interval [CI] 13.87-37.63), sensitivity was 0.84 (95%
      CI 0.75-0.90), specificity was 0.82 (95% CI 0.74-0.89) and area under curve (AUC)
      was 0.90 (95% CI 0.87-0.92). CONCLUSIONS: Based on the meta-analysis of ten case
      controlled studies including 1,074 patients,it was found that the level of
      microRNA-133a in blood serum or plasma maybe used as a diagnostic biomarker of
      AMI.

PMID- 29064536
TI  - Flow-mediated dilatation to relieve puncture-induced radial artery spasm: A pilot
      study.
AB  - BACKGROUND: Puncture-induced radial artery spasm (RAS) may extend the duration of
      coronary an-giography (CAG) or cause transradial access failure. Flow-mediated
      dilatation (FMD), a widely-used noninvasive approach for assessing endothelial
      function, was reported to remove the entrapped radial sheath after percutaneous
      coronary intervention. Herein, the efficacy and safety of FMD in treating
      puncture-induced RAS before transradial CAG was investigated. METHODS: Ninety
      patients with puncture-induced RAS were randomized in a 1:1:1 ratio into three
      groups: FMD group was immediately treated with blockage of brachial artery blood
      for 5 min using a sphygmomanometric cuff and then rapid relief; nitroglycerin
      (NTG) group was administered with 0.5 mg sublingual NTG instantly; and the no
      therapy group was treated with a wait-and-watch strategy. The time of radial
      pulse recovery, and regional and systemic complications were recorded. RESULTS:
      The rate of radial pulse recovery within 30 min in FMD group was significantly
      higher than that in no-therapy group (97% vs. 73%, p = 0.026). The median time to
      return of radial pulse in FMD group and NTG group was significantly shorter than
      that in no-therapy group (7 [6.5-9] min vs. 15 [12-18] min, 8 [7-9] min vs. 15
      [12-18] min, respectively; both p < 0.001). Headache and decreased blood pressure
      were more prevalent in NTG group than those in FMD and no-therapy groups.
      CONCLUSIONS: FMD is a feasible, noninvasive and nonpharmacological approach to
      relieve RAS and facilitate radial artery cannulation after an initial failed
      attempt. (Cardiol J 2018; 25, 1: 1-6).

PMID- 29064537
TI  - In-stent restenosis-prone coronary plaque composition: A retrospective virtual
      histology-intravascular ultrasound study.
AB  - BACKGROUND: The mechanism of in-stent restenosis (ISR) is multifactorial, which
      includes biological, mechanical and technical factors. This study hypothesized
      that increased inflammatory reaction, which is known to be an important
      atherosclerotic process, at a culprit lesion may lead to higher restenosis rates.
      METHODS: The study population consisted of 241 patients who had undergone
      percutaneous coronary intervention with virtual histology-intravascular
      ultrasound (VH-IVUS) and a 9-month follow-up coronary angiography. Compared
      herein is the coronary plaque composition between patients with ISR and those
      without ISR. RESULTS: Patients with ISR (n = 27) were likely to be older (66.2 +/
      9.5 years vs. 58.7 +/- 11.7 years, p = 0.002) and have higher levels of high
      sensitivity C-reactive protein (hs-CRP, 1.60 +/- 3.59 mg/dL vs. 0.31 +/- 0.76
      mg/dL, p < 0.001) than those without ISR (n = 214). VH-IVUS examination showed
      that percent necrotic core volume (14.3 +/- 8.7% vs. 19.5 +/- 9.1%, p = 0.005)
      was higher in those without ISR than those with ISR. Multivariate analysis
      revealed that hs-CRP (odds ratio [OR] 3.334, 95% con-fidence interval [CI] 1.158
      9.596, p = 0.026) and age (OR 3.557, 95% CI 1.242-10.192, p = 0.018) were
      associated with ISR. CONCLUSIONS: This study suggests that ISR is not associated
      with baseline coronary plaque composition but is associated with old age and
      increased expression of the inflammatory marker of hs-CRP. (Cardiol J 2018; 25,
      1: 7-13).

PMID- 29064538
TI  - Morning and afternoon serum cortisol level in patients with post-myocardial
      infarction depression.
AB  - BACKGROUND: Post-myocardial depression is a highly prevalent condition which
      worsens the course and prognosis of coronary artery disease. One possible
      pathogenetic factor is dysregulation of the hypothalamic-pituitary-adrenal axis,
      resulting in cortisol profile disturbances. METHODS: Thirty seven patients
      hospitalized due to a first myocardial infarction (MI) were enrolled in this
      study. The Beck Depression Inventory (BDI) was used to rate the severity of their
      depressive symptoms. Morning and afternoon serum cortisol samples were taken on
      the fifth day of the MI. RESULTS: Depression, defined as BDI >= 10, was present
      in 34.4% of the patients. A statistically significant difference was observed
      between the mean morning and the evening plasma concentrations in patients with
      depression compared to the no-depression group: F (1.29) = 5.0405, p = 0.0328,
      95% CI. CONCLUSIONS: Patients with depressive symptoms directly after MI have a
      flattened diurnal serum cortisol profile. This is particularly expressed in
      patients with longer lasting symptoms.

PMID- 29064539
TI  - Guidezilla extension catheter for percutaneous interventional therapy of complex
      lesions via a transradial approach: Case series from a single-center experience.
AB  - BACKGROUND: Guide catheter extension systems have become one of the most powerful
      tools for address-ing complex lesions during percutaneous coronary intervention
      (PCI), but data on a new-generation rapid exchange extension catheter - the
      Guidezilla catheter - are limited. Summarized herein reports on experience using
      the Guidezilla catheter for complex coronary lesions via a transradial approach
      at the documented institution an evaluation of its safety and efficacy. METHODS:
      A total of 25 patients (19 males and 6 females) who underwent PCI via the radial
      approach with the Guidezilla catheter for adequate back-up support and to
      facilitate equipment delivery were enrolled. The clinical, angiographic and
      procedural data of all 26 procedures in 25 patients (1 patient underwent two PCI
      procedures on different lesions) were collected to evaluate the safety and
      efficacy of this novel equipment. RESULTS: The mean age of the enrolled patients
      was 67.7 +/- 8.41 years old. The mean depth of intuba-tion was 27.90 +/- 12.23
      mm. Stent implantation was successful in 23 out of 26 procedures (88.5%) and
      failed in 3 cases: 1 case of tortuosity and severe angulation in a chronic total
      occlusion lesion; 1 case of an existing type B dissection (NHLBI classification
      system for coronary artery dissection types); and 1 case in which a stent was
      stripped off its balloon. None of the patients experienced coronary dissection,
      perforation, air embolism, pressure dampening or other major complications during
      the procedure. CONCLUSIONS: The Guidezilla extension catheter is an effective and
      safe tool that provides improved back-up support and increases the success rate
      of PCI for complex coronary lesion by radial access.

PMID- 29064540
TI  - Myocardial strain characteristics and outcomes after transcatheter aortic valve
      replacement.
AB  - BACKGROUND: Objective of this study was to make an assessment of standard
      functional and defor-mation parameters (strain) in patients after transcatheter
      aortic valve replacement (TAVR) by cardiac magnetic resonance imaging (CMR) and
      the evaluation of their prognostic impact. METHODS: Patients undergoing TAVR
      received CMR on a 1.5 T whole-body scanner at 3 months after the procedure.
      Deformation parameters (strain, strain rate, velocity, displacement) were
      assessed in lon-gitudinal, circumferential and radial orientation using a feature
      tracking approach. Primary outcome measure was defined according to Valve
      Academic Research Consortium-2 (VARC-2) criteria. RESULTS: Eighty-three patients
      formed the study population. Deformation parameters were significantly reduced in
      all three orientations for strain (longitudinal: -12.1 +/- 5.4% vs. -15.9 +/-
      1.96%, p < 0.0001; radial: 34.4 +/- 15.3% vs. 47.2 +/- 11.4%, p < 0.0001;
      circumferential: -16.8 +/- 4.3% vs. -21.1 +/- 2.5%, p < 0.0001) and strain rate
      (longitudinal: -0.79 +/- 0.33%/s vs. -0.91 +/- 0.23%/s, p = 0.043; radial: 2.5 +/
      1.2%/s vs. 2.9 +/- 0.9%, p = 0.067; circumferential: -1.1 +/- 0.6%/s vs. -1.3 +/
      0.3%/s, p = 0.006) in comparison to a healthy control population. Median follow
      up was 614 days. During this period, 13 endpoints occurred (cumulative event rate
      of 10.7%). Patients with event by trend exhibited poorer strain and strain rate
      in longitudinal and radial orientation without reaching statistical significance
      (longitudinal strain: -11.2 +/- 5.4% vs. -12.3 +/- 5.4%, p = 0.52; longitudinal
      strain rate: -0.73 +/- +/- 0.23%/s vs. 0.80 +/- 0.35%/s, p = 0.53; radial strain:
      29.5 +/- 19.6% vs. 35.2 +/- 14.5%, p = 0.24; radial strain rate: 2.2 +/- 1.6%/s
      vs. 2.6 +/- 1.2%/s, p = 0.31). CONCLUSIONS: Assessment of left ventricular
      deformation parameters by CMR revealed functional abnormalities in comparison to
      healthy controls. Prognostic significance remains to be further investi-gated.

PMID- 29064541
TI  - Hypertrophic reversed palmaris longus muscle: a cadaveric finding.
AB  - Variations of the forearm musculature are vastly described in the literature. The
      palmaris longus muscle is one of the most variable structures of the human body.
      It usually arises from the medial epicondyle of the humerus and inserts itself
      into the palmar aponeurosis. Anatomy textbooks and recent papers state that this
      muscle may act as a weak wrist flexor. The present work aims to report an
      anatomical variation where the palmaris longus muscle was abnormally
      hypertrophied and was completely fleshy throughout the whole forearm. Anatomical
      variations of the palmaris longus may induce symptoms of neurovascular bundle
      compression, especially of the median nerve. The palmaris longus muscle may be
      used in tendon graft or muscle graft, due to its lack of apparent function.
      Furthermore, it is one of the anatomical landmarks for local anaesthesia
      procedures. (Folia Morphol 2018; 77, 2: 403-405).

PMID- 29064542
TI  - Elevated leukocyte count as a harbinger of systemic inflammation, disease
      progression, and poor prognosis: a review.
AB  - Total leukocyte count increases significantly in response to infection, trauma,
      inflammation, and certain diseases. Factors affecting leukocyte count in healthy
      adults include sex, hormonal milieu, genetic inheritance, stress level, diet,
      nutrition, and lifestyle (e.g. tobacco-induced inflammatory changes, chronic
      psychological stress, etc.). To date, numerous studies have reported that high
      but normal leukocyte counts at baseline predict increased cardiovascular and
      noncardiovascular mortality in older adults. Recent findings suggest that
      elevated leukocyte count within the normal range, but especially neutrophil and
      monocyte counts, may be a harbinger of increased systemic inflammation and
      subclinical disease. Moreover, elderly people who tend to have high but normal
      leukocyte counts are at greater risk of cancer, cardiovascular disease, type 2
      diabetes, some other age-related conditions, and they also have increased all
      cause mortality. These results indicate that strong and reliable inflammatory
      markers, such as leukocyte count, may reflect the rate of ageing and therefore
      can predict long-term survival in the elderly. Remarkably, leukocyte count
      correlates positively with genuine markers of systemic inflammation like C
      reactive protein and interleukin 6. Interestingly, some authors conclude that
      leukocyte counts have a stronger prognostic ability with regard to total and
      cardiovascular mortality than total cholesterol or low-density lipoproteins. The
      fact that these inflammatory markers are clinically useful predictors of long
      term survival in the elderly is quite remarkable as these blood parameters are
      included in routine medical check-ups. Therefore, they can be used as simple and
      reliable morphological indicators of chronic systemic inflammation, disease
      progression, and poor prognosis, especially among individuals who are likely to
      develop age-related conditions. Nevertheless, the pathomechanism that links
      elevated but normal leukocyte counts to increased mortality remains poorly
      understood. This review summarises the most important findings on the links
      between leukocyte count, chronic systemic inflammation, and health outcomes in
      older adults. (Folia Morphol 2018; 77, 2: 171-178).

PMID- 29064543
TI  - Effect of valproic acid administration during pregnancy on postnatal development
      of cerebellar cortex and the possible protective role of folic acid.
AB  - BACKGROUND: Valproic acid (VPA), one of the most important antiepileptic drugs,
      proved to be inevitable for epileptic pregnant women to limit the hazards of
      convulsions on the foetuses and mothers. Periconceptional folic acid supple
      mentation was investigated to protect against several birth defects. However, its
      role against VPA cerebellar toxicity was not properly investigated. The present
      study was conducted to evaluate the protective effect of folic acid against VPA
      cerebellar neurotoxicity. MATERIALS AND METHODS: Twenty-four pregnant female
      albino rats were divided into three groups; group I (control group, did not
      receive any drugs), group II (given VPA at a dose of 50 mg/kg body weight once
      daily) and group III (given the same dose of VPA and 400 MUg/kg of body weight
      folic acid once daily). Ten male offspring from each group were sacrificed at two
      ages: at 2 and 12 weeks after birth. Samples of cerebellar cortex were taken and
      prepared for light, electron microscopic examination, glial fibrillary acidic
      protein (GFAP) immunohistochemical study and histomorphometric analysis. RESULTS:
      The present study confirmed the neurotoxic effect of prenatal VPA on the
      cerebellar cortex, especially on Purkinje cells. The cells appeared shrunken,
      reduced in density, disorganised and surrounded by empty haloes. Nuclear damage
      and axon degeneration in the form of vacuolation, loss of organelles and absence
      of neurofilaments with myelin sheath depletion were detected. Concomitant supply
      of folic acid was shown to retain the normal architecture of Purkinje cells with
      their axons and nuclei. In many animals receiving folic acid, the thickness of
      all layers of the cortex increased up to that of the control groups, after being
      markedly reduced in VPA-treated groups. GFAP immunoreaction was also improved
      against the strong positive gliosis detected in VPA-treated groups. CONCLUSIONS:
      The present study confirmed the protective role of folic acid against the
      cerebellar neurotoxic effects of VPA prenatal exposure. It is recommended that
      folic acid supplements should be given to every epileptic pregnant mother treated
      with VPA. (Folia Morphol 2018; 77, 2: 201-209).

PMID- 29064544
TI  - Width of dental arches in patients with maxillary midline diastema.
AB  - BACKGROUND: The aims of the study were as follows: (1) to examine the width of
      the dental arches of patients with maxillary midline diastema and compare it with
      control group; (2) to investigate the impact of the width of upper dental arch on
      the width of diastema. MATERIALS AND METHODS: Diagnostic orthodontic plaster
      models of 102 patients with permanent dentition were studied. Patients were
      divided into two groups: study group with diastema and control group without
      diastema. Patients with severe malocclusion, craniofacial diseases, hypodontia
      and microdontia and pa-tients with periodontal disease were excluded. The
      transpalatal width of palate, premolar and molar arch widths in Pont's points of
      upper and lower jaw were measured using digital calliper. The results were
      statistically analysed. RESULTS: Analysis showed a significant correlation
      between presence of diastema and premolar and molar width of the dental arches
      for both upper and lower jaw. Studied widths were larger in patients with
      diastema compared to the group without diastema. Analysis of the transpalatal
      width showed statistically significant differences between the study group and
      the control group. Analysis of widths of diastema and transpalatal widths showed
      that there was not statistically sig-nificant correlation. CONCLUSIONS: Patients
      with diastema had increased in size in both the premolar and molar width of the
      dental arches. Increase the width affect to both upper and lower dental arch.
      Patients with diastema also were characterised by often occurrence of normal or
      increased of the transpalatal width but the width of the diastema did not
      correlate with the width of the palate. (Folia Morphol 2018; 77, 2: 340-344).

PMID- 29064545
TI  - The morphological characters of the male external genitalia of the European
      hedgehog (Erinaceus Europaeus).
AB  - This study was conducted to depict anatomical characteristics of the penis of he
      dgehog. Seven sexually mature male European hedgehogs were used. Following
      anaesthesia, the animals were scarified with chloroform inhalation. Gross penile
      characteristics such as length and diameter were thoroughly explored and measu
      red using digital callipers. Tissue samples stained with haematoxylin and eosin
      and Masson's trichrome for microscopic analysis. The penis of the European
      hedgehog was composed of a pair of corpus cavernosum penis and the glans penis
      without corpus spongiosum penis. The urethra at the end of penis, protruded as
      urethral process, on both sides of which two black nail-like structures, could be
      observed. The lower part was rounded forming a blind sac (sacculus urethralis)
      with a me-dian split below the urethra. Microscopically, the penile bulb lacked
      the corpus spongiosum penis, but, corpus spongiosum glans was seen at the
      beginning of the free part. In the European hedgehog, entirely stratified
      squamous epithelium of penile urethra, absence of corpus spongiosum penis around
      the urethra and bilateral urethral glands are basically different compared with
      other mammals. This information is expected to contribute to comparative penile
      morphology as well as for testing phylogenic hypotheses and expanding knowledge
      about reproductive biology in this animal. (Folia Morphol 2018; 77, 2: 293-300).

PMID- 29064546
TI  - Wandering spleen: a unique cause of acute abdomen.
AB  - We present the case of a 16-year-old boy presented with 2-week episode of wor
      sening lower abdominal pain. Clinically, there was a tender palpable mass on the
      suprapubic region. Ultrasonography showed an absent spleen at its usual area,
      instead suprapubic mass suggestive of ectopic spleen was identified. An emer
      gency laparotomy revealed a congested spleen in the pelvic cavity. Splenectomy
      was undertaken as it was non-viable. The patient was discharged uneventfully with
      triple vaccinations. We describe this unique entity with its literature review.
      (Folia Morphol 2018; 77, 2: 400-402).

PMID- 29064547
TI  - Comparison of type I collagens and MMP-2 proteins in temporomandibular joint of
      young and old mice.
AB  - BACKGROUND: The effects of ageing on the histopathological changes of tem
      poromandibular joint (TMJ) and the existence and age related alterations of
      immunochemical expressions of type I collagen and matrix metalloproteinase-2 (MMP
      2) proteins was aimed to be displayed. MATERIALS AND METHODS: In this study, 14
      Balb/C type white mice (50- -80 g) were included. Groups were organised as group
      1 - 2-month-old young animals (n = 7) and group 2 - 18-month-old old animals (n =
      7). Of the paraffin embedded tissues 4-5 MUm thick sections were taken and
      immunohisto-chemical stainings of haematoxylin-eosin, type-1 collagen and MMP-2
      were performed. RESULTS: Collagen bundles showed sagittal and oblique
      localisations in the young mice, which were comprised of compact collagen bundle
      layers positioned alterna-tely. While collagen bundle fragmentation was observed
      in the disks of old mice, some disk regions showed ruptures. In the old mice a
      decrease in blood vessels, structural impairments and dilatation in arterioles
      and venules were detected. In the TMJ tissues of the young mice type I collagen
      and MMP-2 expressions were increased, while they were decreased in old mice. In
      the MMP-2 H-score evaluation young mice showed significant increase compared to
      the old mice. CONCLUSIONS: Occurrence of degenerations in the collagen structure
      of TMJ and decimation in the matrix metalloproteases were observed with age.
      (Folia Morphol 2018; 77, 2: 329-334).

PMID- 29064548
TI  - Expression and localisation of FSHR, GHR and LHR in different tissues and
      reproductive organs of female yaks.
AB  - BACKGROUND: This study aimed to investigate the expression and localisation of
      fol-licle stimulating hormone receptor/growth hormone receptor/luteinising
      hormone receptor (FSHR/GHR/LHR) in different tissues and examine the regulatory
      effects of FSHR/GHR/LHR in the reproductive organs of female yaks during luteal
      phase. MATERIALS AND METHODS: The quantitative real-time polymerase chain
      reaction (qRT-PCR) and immunohistochemistry assays were utilised to analyse the
      expression and localisation of FSHR/GHR/LHR in different tissues on female yaks.
      RESULTS: The qRT-PCR results showed that the mRNA expressions of FSHR/GHR/ /LHR
      were significantly different in the non-reproductive organs (p < 0.01); the
      highest expression level was observed in the kidney, cerebellum and lung, whereas
      the lower expression level was observed in the liver and spleen. Im
      munohistochemistry assay results showed that FSHR/GHR/LHR were located in kidney
      tubules, Purkinje cells, cerebellar medulla, alveolar cells and hepato-cytes. In
      addition, the expression levels of FSHR and GHR were considerably higher than LHR
      in the reproductive organs of female yaks during luteal phase (p < 0.01).
      FSHR/GHR/LHR were located in cardiac muscle cells, cerebellar medulla, and theca
      cell lining of reproductive organs. Furthermore, the expression level of FSHR was
      higher than those of GHR and LHR in all examined tissues. CONCLUSIONS: Therefore,
      the expression and localisation of FSHR/GHR/LHR possibly helped to evaluate the
      effects of them in tissue specific expression on female yaks, investigate the
      function and mechanism of FSHR/GHR/LHR in the reproductive organs of female yaks
      during luteal phase. (Folia Morphol 2018; 77, 2: 301-309).

PMID- 29064549
TI  - A comparative morphometric study of the myocardium during the postnatal
      development in normotensive and spontaneously hypertensive rats.
AB  - BACKGROUND: Differences in the size of cardiac muscle cells observed in normal
      and hypertrophic hearts have been assessed through different methodologies.
      Spontaneously hypertensive rats are often used as an experimental model of
      essential hypertension in humans, which allows researchers to study the relation
      between hypertension and cardiac hypertrophy. It has been shown that ventricular
      hypertrophy in mammals progresses and ventricular failure develops in the end
      stage of hypertrophy. The aim of the present study was to analyse a number of
      morphometric markers and compare them between male normotensive Wistar rats (WR)
      and male spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: The total
      number of male WR was 15, distributed in five age groups, each containing three
      animals: 2-week-old; 1-month-old; 3-month--old; 6-month-old; 12-month-old. The
      male SHR were distributed in two age groups, each containing three animals: 1
      month-old (young) and 6-month-old (adult). RESULTS: As aging progressed, both in
      male normotensive WR and in male SHR we noted a statistically significant
      increase in the morphometric parameters thickness of the free wall and the cross
      sectional area of the cardiomyocytes and their nuclei and a decrease in the
      cardiomyocytic density in both ventricles. These changes were more pronounced and
      occurred at an earlier age in SHR. CONCLUSIONS: The present study analyses in
      detail the alterations in the myocardium of the left and right ventricle,
      initiated by age-related hypertrophy, as well as hy-pertrophy induced by arterial
      hypertension. (Folia Morphol 2018; 77, 2: 253-265).

PMID- 29064551
TI  - Organisation of the dopamine neuronal subsets within midbrain of the feathertail
      glider (Acrobates pygmaeus, Acrobatidae, Marsupialia).
AB  - The Marsupial feathertail glider has a unique set of morphological, anatomical
      and behavioural features that make it a promising model for study of primate
      evolution. Among them it has many locomotor adaptations to arboreal life, such as
      diagonal gait of movements, gliding, fast climbing and running along branches.
      These ecological and behavioural specialisations could result in differences in
      anatomy of the brain systems involved in their integration. It is well
      acknowledged that dopaminergic neurons are involved in motor control, motivation
      and cognition. Due to the fact that there are no data on morphological
      organisation of dopaminergic system in the midbrain of this species, we decided
      to investigate it using immunohistochemical and quantitative methods. Our study
      showed that the general distribution and characteristics of the dopaminergic
      cells within midbrain nuclei of the pygmy acrobat is similar to that in other
      species, but it lack the substantia nigra compact part - ventral tier and "tail"
      of the substantia nigra subnuclei. This study provides the first description of
      the dopaminergic cells and nuclei in the midbrain of the feathertail glider and
      we hope it will start interest in the neurobiology of this species.

PMID- 29064550
TI  - Process of neovascularisation compared with pain intensity in tendinopathy of the
      long head of the biceps brachii tendon associated with concomitant shoulder
      disorders, after arthroscopic treatment. Microscopic evaluation supported by
      immunohistochemical.
AB  - BACKGROUND: Tendinopathy of the long head of the biceps brachii tendon (LHBT) is
      one of the most common, painful conditions of the anterior part of the shoulder
      and often coexists with rotator cuff tears. Multifactorial aetiopathology of
      tendi-nopathy is poorly understood; however, several studies indicated that it is
      seen predominantly in areas with decreased vascularity of the tissue; the
      pathology is also characterised by expansive and abundant neovascular in-growth.
      The aim of the study was to investigate the relationship between the
      neovascularisation of proximal part of the LHBT and pain along the bicipital
      groove. MATERIALS AND METHODS: Tissue material was obtained from 28 patients who
      underwent a shoulder arthroscopy and experienced pain along the bicipital groove
      measured using Visual-Analog Scale (VAS) score. CD31 and CD34 molecules were
      visualised by immunohistochemical method to assess biceps tendon neovascula
      risation and quantify it based on a Bonar scoring system. RESULTS: Although all
      patients reported pain prior to arthroscopy (mean VAS score was 7.5), microscopic
      examination did not reveal neovascularisation in all cases. Immunohistochemical
      staining for CD31 and CD34 allowed for very precise visualisation and
      quantification of neovascularisation; however there was also no correlation
      between vessels in-growth scores and pain. CONCLUSIONS: The obtained data suggest
      that neovascularisation process in tendino-pathy is not directly related to pain;
      however, further studies are needed to explain its significance in the LHBT
      tendinopathy. (Folia Morphol 2018; 77, 2: 378-385).

PMID- 29064553
TI  - N-acetylcysteine versus progesterone on the cisplatin-induced peripheral
      neurotoxicity.
AB  - BACKGROUND: Cisplatin-induced peripheral nerve neurotoxicity (CIPN) is the main
      obstacle in cisplatin treatment. The aim of this study was to compare the
      modulatory effects of N-acetylcysteine (NAC) and progesterone on CIPN, because
      there are scarce literature data on the protective effect of the proge-sterone on
      the CIPN. MATERIALS AND METHODS: Twenty-four rats were divided into four groups:
      control, cisplatin-treated, concomitant cisplatin-treated and NAC-treated, and
      concomitant cisplatin-treated and progesterone-treated. Electron microscopic,
      immunohistochemical, real time polymerase chain reaction and histomorphome-tric
      analysis; oxidative/antioxidative markers (MDA/GSH and SOD), neurotoxic/
      neuroprotective markers (iNOS/nNOS), inflammatory mediators (TNF-a and NF-kB) and
      BAX were done. RESULTS: The myelin sheath in the cisplatin-treated group
      elucidated infolding. The myelin was disfigured, degenerated, and extensively
      split with areas of focal loss. The axoplasm was atrophic. Ballooning and
      vacuolations of the mitochon-dria with alterations of Remak bundles structures
      were observed. Fewer of these changes were noted in the NAC and progesterone
      treated groups. Decrease of the antioxidant SOD and GSH (81% and 64%) and
      increase of the oxidant MDA (9 folds), increment of the neurotoxic iNOS (1.9
      folds) and decrement of the neuroprotective nNOS (64%) and elevation of the
      inflammatory mediators' TNF-a and NF-kB (8.3 and 11 folds) in the cisplatin
      treated group. Increase of the antioxidant SOD (1.3 and 2.5 folds) and GSH (120%
      and 79%) and decrease of the oxidant MDA (69% and 88%), decrement of the
      neurotoxic iNOS (56% and 68%) and increment of the neuroprotective nNOS (1.6 and
      one folds) and elevation of the inflammatory mediators' TNF-a and NF-kB were
      observed in the NAC and progesterone-treated groups, respectively. CONCLUSIONS:
      The toxic effect of CIPN might be attributed to either oxidative or severe
      inflammatory stress. Progesterone is efficient in ameliorating these effects;
      however, NAC is better. (Folia Morphol 2018; 77, 2: 234-245).

PMID- 29064552
TI  - Evaluation of the spatial arrangement of Purkinje cells in ataxic rat's
      cerebellum after Sertoli cells transplantation.
AB  - BACKGROUND: Purkinje cells (PCs) pathology is important in cerebellar disorders
      like ataxia. The spatial arrangement of PCs after different treatments has not
      been studied extensively. Immunohistochemistry (IHC) analysis of cerebellum can
      give a proper tool for explaining the pathophysiology of PCs in ataxia. Here we
      stereologically analysed the 3-dimensional spatial arrangement of PCs in the
      cerebellum of rats after ataxia induction with 3-acetylpyridine (3-AP). MATERIALS
      AND METHODS: Ataxia was induced in rats by intraperitoneal injection of 3-AP (65
      mg/kg). Spatial arrangement of PCs for differences in ataxic rats with (3-AP-SC)
      or without (3-AP) Sertoli cells (SCs) transplantation was evaluated using second
      order stereology. The IHC method by using antibodies to anti-calbindin in the
      cerebellum was applied. RESULTS: Our results showed that a random arrangement is
      at larger distances between PCs in 3-AP and 3-Ap-SC groups. Therefore the PCs are
      not normally arranged after 3-AP and SCs transplantation stored the spatial
      arrangements of the cells after ataxia induction in rats. IHC analyse shows that
      number of PCs was significantly improved after the SC transplantation.
      CONCLUSIONS: Segregation of PCs can be observed at some areas in the ataxic rats'
      cerebellum. However, the spatial arrangement of PCs was unchanged in SCs
      transplanted rats. (Folia Morphol 2018; 77, 2: 194-200).

PMID- 29064555
TI  - Does simulation-based training facilitate the integration of human anatomy with
      surgery? A report of a novel Surgical Anatomy Course.
AB  - BACKGROUND: Knowledge of gross anatomy, as a basic core subject, is fundamental
      for medical students and essential to medical practitioners, particularly for
      those intending a surgical career. However, both medical students and clinical
      teachers have found a significant gap in teaching basic sciences and the
      transition into clinical skills. The authors present a Surgical Anatomy Course
      developed to teach the anatomical basis of surgical procedures with particular
      emphasis on laparo-scopic skills while incorporating medical simulation.
      MATERIALS AND METHODS: An evaluation of the students' satisfaction of the
      Surgical Anatomy Course was completed using a mix of multiple choice and open
      ended questions, and a six-point Likert Scale. Questions were asked about the
      students' perceived improvement in surgical and laparoscopic skills. Manual
      skills were assessed using a laparoscopic simulator. RESULTS: Both evaluation of
      the course structure and the general impression of the course were positive. Most
      students believed the course should be an integral part of a modern curriculum.
      The course supported the traditional surgical classes and improved anatomical
      knowledge and strengthened students' confidentiality and facilitated
      understanding and taking surgical rotations. CONCLUSIONS: A medical course
      combining the practical learning of anatomy and surgical-based approaches will
      bring out the best from the students. Medical students positively evaluated the
      Surgical Anatomy Course as useful and benefi-cial regarding understanding
      anatomical structure and relationship necessary for further surgical education.
      (Folia Morphol 2018; 77, 2: 279-285).

PMID- 29064554
TI  - The comparative anatomy of the folds, fossae, and adhesions around the
      duodenojejunal flexure in mammals.
AB  - BACKGROUND: Anatomical knowledge of the duodenojejunal flexure is necessary for
      abdominal surgeries, and also important for physiologic studies about the
      duodenum. But little is known about the anatomy of this region in mammals. Here,
      we examined comparative anatomy to understand the anatomical formation of the
      duodenojejunal flexure in mammals. MATERIALS AND METHODS: The areas around the
      duonenojejunal flexure were ob-served in mouse, rat, dog, pig, and human, and the
      anatomical structures around the duodenojejunal junction in the animals were
      compared with those in human. RESULTS: The superior and inferior duodenal folds,
      and the superior and inferior duodenal fossae were identified in all examined
      humans. In pig, the structures were not clearly identified because the duodenum
      strongly adhered to the retroperitoneum and to the mesocolon. In mouse, rat, and
      dog, only the plica duodenocolica, which is regarded as the animal counterpart of
      the superior duo-denal fold in human, was identified, and other folds or fossae
      were not observed, probably because the duodenum was not fixed to the parietal
      peritoneum in those animals. Transection of the plica duodenocolica could return
      the normally rotated intestine back to the state of non-rotation in rat.
      CONCLUSIONS: This study showed the anatomical similarities and dissimilarities of
      the duodenojejunal flexure among the mammals. Anatomical knowledge of the area is
      useful for duodenal and pancreatic surgeries, and for animal studies about the
      duodenum. (Folia Morphol 2018; 77, 2: 286-292).

PMID- 29064556
TI  - Patients' and therapists' experiences of general change mechanisms during bug-in
      the-eye and delayed video-based supervised cognitive-behavioral therapy. A
      randomized controlled trial.
AB  - OBJECTIVE: This secondary analysis of a randomized controlled trial investigated
      whether bug-in-the-eye (BITE) supervision (live computer-based supervision during
      a psychotherapy session) affects the manner in which patients and therapists
      experience general change mechanisms (GCMs) during cognitive-behavioral therapy
      (CBT). METHOD: A total of 23 therapists were randomized either to the BITE
      condition or the control condition (delayed video-based [DVB] supervision). After
      each session, both patients (BITE: n = 19; DVB: n = 23) and therapists (BITE: n =
      11; DVB: n = 12) completed the Helping Alliance Questionnaire (HAQ) and the
      Bernese Post Session Report (BPSR). The HAQ total score and the 3 secondary
      factors of the BPSR (interpersonal experiences, intrapersonal experiences,
      problem actuation) functioned as GCMs. Multilevel models were performed. RESULTS:
      For patients, GCMs did not develop differently between BITE and DVB during CBT.
      Therapists rated the alliance as well as interpersonal and intrapersonal
      experiences not significantly different between BITE and DVB during CBT, but they
      perceived problem actuation to increase significantly more in BITE than in DVB (p
      < .05). CONCLUSION: BITE supervision might be helpful in encouraging CBT
      therapists to apply interventions, which focus on the activation of relevant
      problems and related emotions.

PMID- 29064557
TI  - Comparative genomics and transcriptomics analysis-guided metabolic engineering of
      Propionibacterium acidipropionici for improved propionic acid production.
AB  - Acid stress induced by the accumulation of organic acids during the fermentation
      of propionibacteria is a severe limitation in the microbial production of
      propionic acid (PA). To enhance the acid resistance of strains, the tolerance
      mechanisms of cells must first be understood. In this study, comparative genomic
      and transcriptomic analyses were conducted on wild-type and acid-tolerant
      Propionibacterium acidipropionici to reveal the microbial response of cells to
      acid stress during fermentation. Combined with the results of previous proteomic
      and metabolomic studies, several potential acid-resistance mechanisms of P.
      acidipropionici were analyzed. Energy metabolism and transporter activity of
      cells were regulated to maintain pH homeostasis by balancing transmembrane
      transport of protons and ions; redundant protons were eliminated by enhancing the
      metabolism of certain amino acids for a relatively stable intracellular
      microenvironment; and protective mechanism of macromolecules were also induced to
      repair damage to proteins and DNA by acids. Transcriptomic data indicated that
      the synthesis of acetate and lactate were undesirable in the acid-resistant
      mutant, the expression of which was 2.21-fold downregulated. In addition,
      metabolomic data suggested that the accumulation of lactic acid and acetic acid
      reduced the carbon flow to PA and led to a decrease in pH. On this basis, we
      propose a metabolic engineering strategy to regulate the synthesis of lactic acid
      and acetic acid that will reduce by-products significantly and increase the PA
      yield by 12.2% to 10.31 +/- 0.84 g/g DCW. Results of this study provide valuable
      guidance to understand the response of bacteria to acid stress and to construct
      microbial cell factories to produce organic acids by combining systems biology
      technologies with synthetic biology tools.

PMID- 29064558
TI  - Effect of different light spectra on the pigmentation of stored elephant garlic.
AB  - BACKGROUND: In the present study high-brightness light-emitting diodes were used
      to investigate the influence of different light spectra on garlic discoloration
      at different humidity levels and temperature. Many processes involved in the
      discoloration process of garlic/leek during storage under different conditions
      remain unanswered. For this reason in this study the ability of specific light
      spectra to enhance the production of desirable pigments has been evaluated in
      elephant garlic. It is well known that the pigments involved in the discoloration
      reaction are of great interest because of their potential ability to increase the
      nutritional value and health benefits of the food. RESULTS: In the present study,
      we show how the chlorophyll content of the sprout increases directly
      proportionally to the wavelength of the light tested; green/blue light delays the
      greening process of garlic young shoots whilst red/infra-red light irradiance
      conditions increase the greening process at different storage temperatures and
      humidity. Moreover different lights in the visible spectrum have been observed to
      stimulate and enhance the outer layer purple coloration. CONCLUSION: The use of
      different lights to modulate garlic pigmentation has been demonstrated and, in
      particular, the utilisation of red/green/blue lights and lower temperature
      resulted in higher red/pink pigments production supporting the hypothesis that
      this process involves more than one light to be fully performed and the low
      temperature is a condition that influences the formation of these products. (c)
      2017 Society of Chemical Industry.

PMID- 29064560
TI  - Chemical imaging of a Symbiodinium sp. cell using synchrotron infrared
      microspectroscopy: a feasibility study.
AB  - The symbiotic relationship between corals and Symbiodinium spp. is the key to the
      success and survival of coral reef ecosystems the world over. Nutrient exchange
      and chemical communication between the two partners provides the foundation of
      this key relationship, yet we are far from a complete understanding of these
      processes. This is due, in part, to the difficulties associated with studying an
      intracellular symbiosis at the small spatial scales required to elucidate
      metabolic interactions between the two partners. This feasibility study, which
      accompanied a more extensive investigation of fixed Symbiodinium cells (data
      unpublished), examines the potential of using synchrotron radiation infrared
      microspectroscopy (SR-IRM) for exploring metabolite localisation within a single
      Symbiodinium cell. In doing so, three chemically distinct subcellular regions of
      a single Symbiodinium cell were established and correlated to cellular function
      based on assignment of diagnostic chemical classes.

PMID- 29064559
TI  - The impact of short-term UV irradiation on grains of sensitive and tolerant
      cereal genotypes studied by EPR.
AB  - BACKGROUND: UV irradiation has ionisation character and leads to the generation
      of reactive oxygen species (ROS). The destructive character of ROS was observed
      among others during interaction of cereal grains with ozone and was caused by
      changes in structures of biomolecules leading to the formation of stable organic
      radicals. That effect was more evident for stress sensitive genotypes. In this
      study we investigated the influence of UV irradiation on cereal grains
      originating from genotypes with different tolerance to oxidative stress. RESULTS:
      Grains and their parts (endosperm, embryo and seed coat) of barley, wheat and oat
      were subjected to short-term UV irradiation. It was found that UV caused the
      appearance of various kinds of reactive species (O2-* , H2 O2 ) and stable
      radicals (semiquinone, phenoxyl and carbon-centred). Simultaneously, lipid
      peroxidation occurred and the organic structure of Mn(II) and Fe(III) complexes
      become disturbed. CONCLUSIONS: UV irradiation causes damage of main biochemical
      structures of plant tissues, the effect is more significant in sensitive
      genotypes. In comparison with ozone treatment, UV irradiation leads to stronger
      destruction of biomolecules in grains and their parts. It is caused by the high
      energy of UV light, facilitating easier breakage of molecular bonds in
      biochemical compounds. (c) 2017 Society of Chemical Industry.

PMID- 29064561
TI  - Reactivity and structural evolution of urchin-like Co nanostructures under
      controlled environments.
AB  - In situ transmission electron microscopy (TEM) of samples in a controlled gas
      environment allows for the real time study of the dynamical changes in
      nanomaterials at high temperatures and pressures up to the ambient pressure (105
      Pa) with a spatial resolution close to the atomic scale. In the field of
      catalysis, the implementation and quantitative use of in situ procedures are
      fundamental for a better understanding of the behaviour of catalysts in their
      environments and operating conditions. By using a microelectromechanical systems
      (MEMS)-based atmospheric gas cell, we have studied the thermal stability and the
      reactivity of crystalline cobalt nanostructures with initial 'urchin-like'
      morphologies sustained by native surface ligands that result from their synthesis
      reaction. We have evidenced various behaviors of the Co nanostructures that
      depend on the environment used during the observations. At high temperature under
      vacuum or in an inert atmosphere, the migration of Co atoms towards the core of
      the particles is activated and leads to the formation of carbon nanostructures
      using as a template the initial multipods morphology. In the case of reactive
      environments, for example, pure oxygen, our investigation allowed to directly
      monitor the voids formation through the Kirkendall effect. Once the
      nanostructures were oxidised, it was possible to reduce them back to the metallic
      phase using a dihydrogen flux. Under a pure hydrogen atmosphere, the sintering of
      the whole structure occurred, which illustrates the high reactivity of such
      structures as well as the fundamental role of the present ligands as morphology
      stabilisers. The last type of environmental study under pure CO and syngas (i.e.
      a mixture of H2 :CO = 2:1) revealed the metal particles carburisation at high
      temperature.

PMID- 29064563
TI  - Comparison of purification strategies for antibodies used in a broad spectrum
      host cell protein immunoassay.
AB  - Host cell proteins (HCPs) are a heterogeneous mixture of impurities that should
      be minimized in bulk preparations of biotechnologically produced medicines.
      Immunoassays are commonly used to detect and measure HCPs in therapeutic
      products, and a successful assay is directly dependent on the quality of the
      polyclonal antibodies (pAbs) used. These pAbs are enriched from antisera of
      animals immunized with a broad mixture of HCPs, but there is limited information
      regarding the best strategy for purification of these critical reagents. The use
      of protein A or protein G affinity chromatography results in purified pAbs that
      are not entirely HCP-specific, while the use of HCP affinity chromatography
      results in a more specific pAb population but may be harder to recover fully. In
      theory, both approaches have advantages and disadvantages for generating optimal
      reagents. In this study, we compared reagents from these two purification
      procedures using the same starting material, as well as those from a step-wise
      combination of the two by evaluating purity, concentration, reagent coverage by
      Western blotting, and performance in an enzyme-linked immunosorbent assay
      (ELISA). This study demonstrates that pAbs purified by each of the methods are
      very similar in terms of sensitivity, the ability to recognize a broad range of
      HCPs, and overall performance in an ELISA measuring a range of HCPs in upstream
      process and final drug substance (DS) samples.

PMID- 29064562
TI  - Bioactive compounds from orange epicarp to enrich fish burgers.
AB  - BACKGROUND: The orange industry produces considerable amounts of by-products,
      traditionally used for animal feed or fuel production. Most of these by-products
      could be used as functional ingredients. To assess the potential food application
      of orange epicarp, different percentages of micro-encapsulated orange extract
      were added to fresh fish burgers. Then, an in vitro digestion was also carried
      out, before and after micro-encapsulation, to measure the bio-accessibility of
      the active compounds. RESULTS: A significant increase of bio-accessibility of
      bioactive compounds has been observed in the orange epicarp extract after micro
      encapsulation by spray-drying. From the sensory point of view, the fish sample
      enriched with 50 g kg-1 micro-encapsulated extract was the most comparable to the
      control burger, even if it showed a higher phenolic, flavonoid and carotenoid bio
      accessibility. CONCLUSION: Orange epicarp may be used as a food additive to
      enhance the health content of food products. The micro-encapsulation is a valid
      technique to protect the bioactive compounds and increase their bio
      accessibility. (c) 2017 Society of Chemical Industry.

PMID- 29064564
TI  - Directed evolution of polypropylene and polystyrene binding peptides.
AB  - Surface functionalization of biological inert polymers (e.g., polypropylene PP;
      polystyrene PS) with material binding peptides facilitates an efficient
      immobilization of enzymes, bioactive peptides or antigens at ambient temperature
      in water. The developed robust directed evolution protocol enables to tailor
      polymer binding anchor peptides (PBPs) for efficient binding under application
      conditions. Key for a successful directed evolution campaign was to develop an
      epPCR protocol with a very high mutation frequency (60 mutations/kb) to ensure
      sufficient diversity in PBPs (47 aas LCI: "liquid chromatography peak I"; 44 aas
      TA2: "Tachystatin A2"). LCI and TA2 were genetically fused to the reporter egfp
      to quantify peptide binding on PP and PS by fluorescence analysis. The Peptide
      Polymer evolution protocol (PePevo protocol) was validated in two directed
      evolution campaigns for two PBPs and polymers (LCI: PP; TA2: PS). Surfactants
      were used as selection pressure for improved PBP binders (non-ionic surfactant
      Triton X-100; 1 mM for LCI-PP // anionic surfactant LAS; 0.5 mM for TA2-PS).
      PePevo yielded an up to three fold improved PP-binder (LCI-M1-PP: I24T, Y29H, E42
      K and LCI-M2-PP: D31V, E42G) and an up to six fold stronger PS-binder (TA2-M1-PS:
      R3S, L6P, V12 K, S15P, C29R, R30L, F33S, Y44H and TA2-M2-PS: F9C, C24S, G26D,
      S31G, C41S, Y44Q).

PMID- 29064565
TI  - Effect of culture density on biomass production and light utilization efficiency
      of Synechocystis sp. PCC 6803.
AB  - The viability of large-scale microalgae cultivation depends on providing optimal
      growth conditions, for which a key operational parameter is culture density.
      Using Synechocystis sp. PCC 6803, we conducted a series of fixed-density, steady
      state experiments and one batch-growth experiment to investigate the role of
      culture density on biomass production and light utilization efficiency. In all
      cases, the fixed-density, steady-state experiments and batch-growth experiment
      showed good agreement. The highest biomass production rates (260 mg L-1  d-1 )
      and efficiency for converting light energy to biomass (0.80 MUg (MUmol photons)-1
      ) occurred together at a culture density near 760 mg L-1 , which approximately
      corresponded to the lowest culture density where almost all incident light was
      absorbed. The ratio of OD680 /OD735 increased with culture density up to the
      point of maximum productivity, where it plateaued (at a value of 2.4) for higher
      culture densities. This change in OD680 /OD735 indicates a photoacclimation
      effect that depended on culture density. Very high culture densities led to a
      sharp decline in efficiency of biomass production per photons absorbed, likely
      due to a combination of increased decay relative to growth, metabolic changes due
      to cell-cell interactions, and photodamage due to mixing between regions with
      high light intensity and zero light intensity.

PMID- 29064566
TI  - Generation and Characterization of Functional Human Hypothalamic Neurons.
AB  - Neurons in the hypothalamus orchestrate homeostatic physiological processes and
      behaviors essential for life. Defects in the function of hypothalamic neurons
      cause a spectrum of human diseases, including obesity, infertility, growth
      defects, sleep disorders, social disorders, and stress disorders. These diseases
      have been studied in animal models such as mice, but the rarity and relative
      inaccessibility of mouse hypothalamic neurons and species-specific differences
      between mice and humans highlight the need for human cellular models of
      hypothalamic diseases. We and others have developed methods to differentiate
      human pluripotent stem cells (hPSCs) into hypothalamic neurons and related cell
      types, such as astrocytes. This protocol builds on published studies by providing
      detailed step-by-step instructions for neuronal differentiation, quality control,
      long-term neuronal maintenance, and the functional interrogation of hypothalamic
      cells by calcium imaging. Together, these protocols should enable any group with
      appropriate facilities to generate and study human hypothalamic cells. (c) 2017
      by John Wiley & Sons, Inc.

PMID- 29064567
TI  - Learning from the past: reflections on recently completed myasthenia gravis
      trials.
AB  - Recently competed clinical trials of therapeutics for myasthenia gravis have
      varied widely in design, but also perhaps in less explicit ways. We explore ways
      in which these design characteristics may have influenced recruitment and
      results, as well as the implications for forthcoming studies. Trial eligibility
      criteria may inadvertently select for incident versus prevalent cases or patients
      with relatively mild versus more severe disease. Trial enrichment with patients
      who have relatively mild disease may limit the sensitivity of the trial to detect
      a therapeutic effect. Enrichment for patients with more severe disease may
      introduce confounds caused by regression toward the mean. Overly narrow
      eligibility may limit the generalizability of results. An exclusive focus on
      incident cases may hamper recruitment, as may many other factors, such as access
      to the experimental therapeutic treatment outside of the trial or following
      completion of the double-blind treatment period. We illustrate how other design
      characteristics (e.g., treatment duration, strategy for steroid tapering,
      selection of the primary outcome, and principal analytic approach) may affect the
      sensitivity of a trial to demonstrate therapeutic effects. Finally, we consider
      the importance of placebo effects, being careful to differentiate these from
      therapeutic effects observed in the placebo group, and discuss how the use of
      combined outcome measures may minimize placebo effects.

PMID- 29064568
TI  - Utility of preoperative Holter monitoring in children undergoing extracardiac
      conduit Fontan operation.
AB  - BACKGROUND: In patients undergoing extracardiac conduit Fontan (ECF) who require
      postoperative pacing, epicardial leads are usually required because of anatomical
      constraints. If indicated, these could be conveniently placed at the time of ECF.
      We have routinely performed ambulatory 24-hour Holter monitoring before ECF to
      determine the presence or absence of preoperative sinus node dysfunction, in an
      attempt to avoid repeat sternotomy at a later time. METHODS: We performed a
      retrospective study of all patients undergoing ECF from January 2000 to December
      2015. RESULTS: Two hundred sixteen patients met inclusion criteria. Patients were
      separated into two groups, those with preoperative Holter monitoring (PHM, n =
      150) and those without (No-PHM, n = 66). Ten patients (4.6%) underwent permanent
      pacemaker implantation at the time of ECF (eight patients [5.3%] in PHM vs two
      patients [3.0%] in No-PHM, P = 0.46). There were seven (3.2%) patients who
      underwent pacemaker implantation after ECF requiring repeat sternotomy (four
      patients [2.7%] in PHM vs three patients [4.5%] in No-PHM, P = 0.47). Fourteen
      (6.5%) patients underwent permanent epicardial lead placement without a pulse
      generator at the time of ECF. None from this group underwent pacemaker
      implantation to date (median follow-up of 5.7 years). The overall incidence of
      pacemaker implantation was 9.3% (20 patients). CONCLUSIONS: In our series,
      arrhythmia disturbances requiring pacing after ECF occurred in just over 9% of
      patients. While PHM in those patients may help predict which patients might
      require postoperative pacing, this approach did not result in a significant
      decrease in those patients requiring repeat sternotomy for pacemaker
      implantation.

PMID- 29064569
TI  - A modified Maquet-tibial tuberosity advancement technique for treatment of canine
      cranial cruciate ligament disease: Short term outcome and complications.
AB  - OBJECTIVE: To describe and report the outcomes of a novel modified Maquet-tibial
      tuberosity advancement (mTTA) technique in dogs with naturally occurring cranial
      cruciate ligament (CCL) rupture, compared to a traditional tibial tuberosity
      advancement (tTTA) technique. STUDY DESIGN: Descriptive report and retrospective
      clinical cohort study. SAMPLE POPULATION: Dogs (n = 70) treated via tibial
      tuberosity advancement (TTA). METHODS: Medical records (2013-2015) of dogs
      treated for CCL rupture via TTA were reviewed for: signalment, findings on
      physical examination, procedure (tTTA or mTTA), radiographs, complications, and
      outcome. Radiographs were retrospectively evaluated for patellar tendon
      thickness, evidence of tibial crest fractures, and implant placement.
      Intraoperative and postoperative complications and outcome were compared between
      procedures. RESULTS: A total of 70 cases met inclusion criteria, 35 of each
      procedure (tTTA or mTTA). The mTTA procedure was successfully performed with good
      clinical and radiographic outcomes. The only difference in outcomes detected
      between groups is that dogs were more lame 2 weeks after tTTA than mTTA group.
      CONCLUSION: The mTTA technique represents a safe, repeatable alternative to the
      tTTA, with similar outcome and complication rates.

PMID- 29064570
TI  - Effects of scaffold microstructure and low intensity pulsed ultrasound on
      chondrogenic differentiation of human mesenchymal stem cells.
AB  - The effects of low intensity pulsed ultrasound (LIPUS) on proliferation and
      chondrogenic differentiation of human mesenchymal stem cells (hMSCs) seeded on 3D
      printed poly-(ethylene glycol)-diacrylate (PEG-DA) scaffolds with varying pore
      geometries (square and hexagonal channels) were investigated. The scaffold with
      square pores resulted in higher hMSC growth and chondrogenic differentiation than
      a solid or a hexagonally porous scaffold. The optimal LIPUS parameters at 1.5 MHz
      were found to be 100 mW/cm2 and 20% duty cycle. LIPUS stimulation increased
      proliferation by up to 60% after 24 hr. For chondrogenesis, we evaluated key
      cartilage biomarkers abundant in cartilage tissue; glycosaminoglycan (GAG), type
      II collagen and total collagen. LIPUS stimulation enhanced GAG synthesis up to
      16% and 11% for scaffolds with square and hexagonal patterns, respectively, after
      2 weeks. Additionally, type II collagen production increased by 60% and 40% for
      the same patterns, respectively under LIPUS stimulation after 3 weeks. These
      results suggest that LIPUS stimulation, which has already been approved by FDA
      for treatment of bone fracture, could be a highly efficient tool for tissue
      engineering in combination with 3D printing and hMSCs to regenerate damaged
      cartilage tissues.

PMID- 29064572
TI  - Changing pattern of prevalence, genetic diversity, and mixed infections of
      viruses associated with acute gastroenteritis in pediatric patients in New Delhi,
      India.
AB  - There are very few studies that have assessed multiple viral agents causing Acute
      Gastroenteritis (AGE) in India. The present study compared the changing pattern
      of prevalence and genetic diversity of five enteric viruses associated with acute
      diarrhea in Delhi children within a gap of 5 years. Fecal samples were collected
      from diarrheal children (<4 years) during two winter seasons: year 2009-2010 (n =
      59) and year 2014-2015 (n = 85). Samples were individually tested for rotavirus
      A, norovirus, astrovirus, adenovirus, and sapovirus using EIA/RT-PCR and
      genetically characterized by phylogenetic analysis. Rotavirus was the most
      predominant (54.9%) virus followed by norovirus (25.7%), astrovirus (8.3%), and
      adenovirus (4.9%) with rare detection of sapovirus (0.7%). While detection rate
      increased for both rotavirus (49.2-58.8%) and astrovirus (5.1-10.6%), norovirus
      detection rate decreased (30.5-22.4%) from 2009 to 2015. During the same time
      period, adenovirus detection remained low (4.7-5.1%). Interestingly, mixed
      infections increased from 8.5% to 16.5% after 5 years. G1P[8] rotavirus strain
      was found most predominant (40%). Both type-1 and 8 astroviruses were detected.
      Single sapovirus detected was of genotype GII.1. Both GI (GI.5, GI.3) and GII
      (GII.1, GII.4, GII.7, GII.21, GII.13) genogroups of norovirus were detected. Of
      particular significance was the first detection of other NoV genotypes (besides
      GII.4 and GI.3) in Delhi. This is also the first report of NoV GI.5 from India. A
      change in prevalence pattern and increased diversity from 2009 to 2015 emphasizes
      the need for continued enteric virus surveillance to help measure the impact of
      new diarrhea vaccine(s) introduced in India.

PMID- 29064571
TI  - Estimation of the Potential Effectiveness of Lowering the Blood Alcohol
      Concentration (BAC) Limit for Driving from 0.08 to 0.05 Grams per Deciliter in
      the United States.
AB  - BACKGROUND: In 2013, the National Transportation Safety Board (NTSB) issued a
      report recommending that states lower the illegal blood alcohol concentration
      (BAC) limit for driving from 0.08 to 0.05 g/dl. The NTSB concluded that there is
      a strong evidence-based foundation for a BAC limit of 0.05 or lower. Most
      industrialized nations have already enacted a 0.05 illegal BAC limit. This study
      was undertaken to contribute to the scientific evidence as to whether lowering
      the BAC limit to 0.05 will be an effective alcohol policy in the United States.
      METHODS: We accomplished our objective by: (i) conducting a meta-analysis of
      qualifying international studies to estimate the range and distribution of the
      most likely effect size from a reduction to 0.05 BAC or lower; (ii) translating
      this synthesis toward estimating the effects of reducing the current 0.08 BAC
      limit to 0.05 in the United States; and (iii) estimating the life-saving benefits
      of the proposed 0.03 reduction in the driving limit from 0.08 to 0.05 BAC.
      RESULTS: In our meta-analysis of studies on lowering the BAC limit in general, we
      found a 5.0% decline in nonfatal alcohol-related crashes, a 9.2% decline in fatal
      alcohol-related crashes from lowering the BAC to 0.08, and an 11.1% decline in
      fatal alcohol-related crashes from lowering the BAC to 0.05 or lower. We estimate
      that 1,790 lives would be saved each year if all states adopted a 0.05 BAC limit.
      CONCLUSIONS: This study provides strong evidence of the relationship between
      lowering the BAC limit for driving and the general deterrent effect on alcohol
      related crashes.

PMID- 29064573
TI  - Effects of magnetic field orientation and strength on the treatment planning of
      nonsmall cell lung cancer.
AB  - PURPOSE: Magnetic resonance image-guided radiotherapy (MRgRT) has the potential
      to increase the accuracy of radiation treatment delivery. Several research groups
      have developed hybrid MRgRT devices differing by radiation source used and
      magnetic field orientation and strength. In this work, we investigate the impact
      of different magnetic field orientations and strengths on the treatment planning
      of nonsmall cell lung cancer patients (NSCLC). METHODS: A framework using the in
      house developed treatment planning system matRad and the EGSnrc Monte Carlo code
      system was introduced to perform Monte Carlo-based treatment planning in the
      presence of a magnetic field. A specialized spectrum-based source model for the
      beam qualities of 6 MV and cobalt-60 was applied. Optimized plans for
      stereotactic body radiation therapy (SBRT) and intensity-modulated radiation
      therapy (IMRT) were generated for four NSCLC patients in the presence of
      different magnetic field orientations and strengths which are applied in hybrid
      MRgRT devices currently under development or in clinical use. RESULTS: SBRT and
      IMRT treatment planning could be performed with consistent plan quality for all
      magnetic field setups. Only minor effects on the treatment planning outcome were
      found in the case of magnetic fields orientated perpendicular to the beam
      direction. Compared to the perpendicular magnetic field orientation, the inline
      orientation showed the capability to reduce the dose to lung while maintaining
      equal target coverage. Particularly for tumors with a central position in lung, a
      distinct dose reduction was obtained which led to a maximum reduction of mean
      lung dose by 18.5% (0.5 Gy), when applying a 1 T inline magnetic field.
      CONCLUSION: All plans generated in this work obtained dose metrics within
      clinical constraints according to RTOG guidelines. When considering conventional
      dose metrics, no detrimental effects due to the magnetic fields were observed on
      the dose to the tumor or to organs at risk. An evaluation of the effects on skin
      dose was not ascertainable due to the simplified specification of the source
      model used. By accounting for the magnetic field during treatment planning, a
      dose reduction in lung could be achieved for inline-oriented magnetic fields. An
      inline orientation of the magnetic field therefore showed a potential benefit
      when treating NSCLC with MRgRT.

PMID- 29064575
TI  - DNA detection of JC and BK virus in archival urine cytospin slides.
AB  - To identify decoy cells, cytological examination was performed in urine cytospin
      slides. Decoy cells are related to Polyomaviruses (JC virus [JCV] and BK virus
      [BKV]), which are recognized worldwide due to potential infection and morbidity
      in kidney transplant recipients. Cytologically, it is difficult to evaluate the
      cytopathic effect of JCV and BKV in urine of patients with urothelial neoplasia.
      For this reason, there is a need for molecular approaches. To evaluate the
      incidence of BKV and JCV DNA in archival slides of urine cytospin material with
      benign and malignant characteristics. A total of 176 urine specimens were used
      for cytological examination of neoplastic or decoy cells. The samples were
      analyzed for the presence of JCV and BKV, by polymerase chain reaction (PCR) in
      DNA Isolated from archival slides of urine cytospin material. A typical samples
      (n = 48) were compared with the remaining 128 samples without atypia/neoplasia
      for the presence of JCV or BKV DNA. A statistically nonsignificant result was
      observed correlating the presence of JCV or BKV. The results show that DNA
      Isolated from archival slides of urine cytospin material can be used for
      detection of BKV and JCV.

PMID- 29064576
TI  - Molecular characterization of hepatitis C virus in end-stage renal disease
      patients under hemodialysis.
AB  - New direct-acting antiviral (DAA) agents are in development or already approved
      for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness
      of these drugs is related to the previous existence of resistant variants.
      Certain clinical conditions can allow changes in immunological characteristics of
      the host and even modify genetic features of viral populations. The aim of this
      study was to perform HCV molecular characterization from samples of end-stage
      renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger
      sequencing were used to obtain genetic information from the NS5B partial region
      of a cohort composed by 86 treatment-naive patients. Genomic sequences from the
      Los Alamos databank were employed for comparative analysis. Bioinformatics
      methodologies such as phylogenetic reconstructions, informational entropy, and
      mutation analysis were used to analyze datasets separated by geographical
      location, HCV genotype, and renal function status. ESRD-HD patients presented HCV
      genotypes 1a (n = 18), 1b (n = 16), 2a (n = 2), 2b (n = 2), and 3a (n = 4).
      Control subjects were infected with genotypes 1a (n = 11), 1b (n = 21), 2b (n =
      4), and 3a (n = 8). Dataset phylogenetic reconstruction separated HCV subtype 1a
      into two distinct clades. The entropy analysis from the ESRD-HD group revealed
      two amino acid positions related to an epitope for cytotoxic T lymphocytes and T
      helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also,
      genotype 1a ERSD-HD patients had a higher mean of amino acids changes in
      comparison to control group patients. The identification of specific mutations on
      epitopes and high genetic diversity within the NS5B HCV partial protein in
      hemodialysis patients can relate to host immunological features and geographical
      distribution patterns. This genetic diversity can affect directly the new DAA's
      resistance mechanisms.

PMID- 29064574
TI  - Adolescent mothers' anthropometrics and grandmothers' schooling predict infant
      anthropometrics in Ethiopia, India, Peru, and Vietnam.
AB  - We investigated intergenerational associations of adolescent mothers' and
      grandmothers' anthropometrics and schooling with adolescent mothers' offspring's
      anthropometrics in Ethiopia, India, Peru, and Vietnam. We examined birthweight (n
      = 283), birthweight Z-score (BWZ), conditional growth in weight-for-age Z-score
      (cWAZ, residuals from a regression of WAZ at last survey round on BWZ, sex, and
      age), and height-for-age Z-score (HAZ) of children born to older cohort
      adolescent girls in the Young Lives study. Our key independent variables were
      adolescent mothers' body size: HAZ and body-mass-index-for-age Z-score (BMIZ) at
      age 8, conditional HAZ (cHAZ, residuals from a regression of HAZ at the end of a
      growth period on prior HAZ, age, and sex), conditional BMIZ growth (cBMIZ,
      calculated analogously), and grandmaternal BMIZ, HAZ, and schooling. We adjusted
      for child, maternal, and household characteristics. Adolescent mothers' cHAZ
      (ages 8-15) predicted birthweight (beta = 130 g, 95% confidence interval (CI) 31
      228), BWZ (beta = 0.31, CI 0.09-0.53), and cWAZ (beta = 0.28, CI 0.04-0.51).
      Adolescent mothers' BMIZ at age 8 predicted birthweight (beta = 79 g, CI 16-43)
      and BWZ (beta = 0.22, CI 0.08-0.36). Adolescent mothers' cBMIZ (ages 12-15)
      predicted child cWAZ and HAZ. Grandmothers' schooling predicted grandchild
      birthweight (beta = 22 g, CI 1-44) and BWZ (beta = 0.05, CI 0.01-0.10).

PMID- 29064577
TI  - Wearable cardioverter defibrillators in schools: A guide for parents and
      educators.
AB  - Keeping children safe is a goal for everyone. To stay safe, some children need a
      wearable cardioverter defibrillator (WCD). WCDs protect individuals who are at
      risk for life-threatening arrhythmias. The LifeVest(r) (ZOLL, Pittsburgh, PA,
      USA) is a WCD that identifies, records, and treats potentially life-threatening
      abnormal heartbeats, or arrhythmias. The WCD will provide electrical energy to
      the heart with up to five high-energy shocks if a potentially dangerous cardiac
      arrhythmia is detected. This type of arrhythmia, if not treated within a short
      time period (less than 2 minutes), can result in disruption of blood flow to the
      brain and other vital organs (that is, a sudden cardiac arrest), and death can
      occur within minutes. A shock delivered by the LifeVest can terminate an
      arrhythmia and restore a normal heart rhythm and blood flow to the body. In
      December 2015, the Food and Drug Administration approved the LifeVest for
      patients under 18 years old. The purpose of this guide is to serve as a resource
      for parents and educators, to promote awareness of the LifeVest, and to answer
      questions about the safety of the LifeVest in schools.

PMID- 29064578
TI  - A diagnosis and treatment gap for thiamine deficiency disorders in sub-Saharan
      Africa?
AB  - Staple diets that are deficient in thiamine can result in low body thiamine
      levels, which may be subclinical or may manifest as a thiamine-deficiency
      syndrome. In many communities in the developing countries of Africa, the staple
      diets of polished rice or processed cassava are deficient in thiamine, and thus
      the communities are at high risk for marginal or frank thiamine deficiency unless
      their diets are supplemented by other sources of thiamine, such as protein meals
      and vegetables. African communities with large numbers of individuals in low
      socioeconomic strata are more likely to subsist on a monotonous diet of rice or
      cassava with minimal or no protein supplementation and are therefore particularly
      at risk of thiamine-deficiency disorders. Indeed, there is evidence of widespread
      biochemical thiamine deficiency from community-based studies in Africa. The
      protean manifestations of thiamine deficiency disorders in the developing
      countries of Africa are presented in this paper. We present evidence supporting
      the contention that there is a diagnosis and treatment gap for thiamine
      deficiency disorders in Africa. We discuss research and clinical options for
      bridging the putative diagnosis and treatment gap for thiamine-deficiency
      disorders in the developing countries of Africa.

PMID- 29064579
TI  - Quantitative imaging of peripheral trabecular bone microarchitecture using MDCT.
AB  - PURPOSE: Osteoporosis associated with reduced bone mineral density (BMD) and
      microarchitectural changes puts patients at an elevated risk of fracture. Modern
      multidetector row CT (MDCT) technology, producing high spatial resolution at
      increasingly lower dose radiation, is emerging as a viable modality for
      trabecular bone (Tb) imaging. Wide variation in CT scanners raises concerns of
      data uniformity in multisite and longitudinal studies. A comprehensive cadaveric
      study was performed to evaluate MDCT-derived Tb microarchitectural measures. A
      human pilot study was performed comparing continuity of Tb measures estimated
      from two MDCT scanners with significantly different image resolution features.
      METHOD: Micro-CT imaging of cadaveric ankle specimens (n=25) was used to examine
      the validity of MDCT-derived Tb microarchitectural measures. Repeat scan
      reproducibility of MDCT-based Tb measures and their ability to predict mechanical
      properties were examined. To assess multiscanner data continuity of Tb measures,
      the distal tibias of 20 volunteers (age:26.2+/-4.5Y,10F) were scanned using the
      Siemens SOMATOM Definition Flash and the higher resolution Siemens SOMATOM Force
      scanners with an average 45-day time gap between scans. The correlation of Tb
      measures derived from the two scanners over 30% and 60% peel regions at the 4% to
      8% of distal tibia was analyzed. RESULTS: MDCT-based Tb measures characterizing
      bone network area density, plate-rod microarchitecture, and transverse trabeculae
      showed good correlations (r?0.85,0.92) with the gold standard micro-CT-derived
      values of matching Tb measures. However, other MDCT-derived Tb measures
      characterizing trabecular thickness and separation, erosion index, and structure
      model index produced weak correlation (r<0.8) with their micro-CT-derived values.
      Most MDCT Tb measures were found repeatable (ICC?0.94,0.98). The Tb plate-width
      measure showed a strong correlation (r = 0.89) with experimental yield stress,
      while the transverse trabecular measure produced the highest correlation (r =
      0.81) with Young's modulus. The data continuity experiment showed that, despite
      significant differences in image resolution between two scanners (10% MTF along
      xy-plane and z-direction - Flash: 16.2 and 17.9 lp/cm; Force: 24.8 and 21.0
      lp/cm), most Tb measures had high Pearson correlations (r > 0.95) between values
      estimated from the two scanners. Relatively lower correlation coefficients were
      observed for the bone network area density (r = 0.91) and Tb separation (r =
      0.93) measures. CONCLUSION: Most MDCT-derived Tb microarchitectural measures are
      reproducible and their values derived from two scanners strongly correlate with
      each other as well as with bone strength. This study has highlighted those MDCT
      derived measures which show the greatest promise for characterization of bone
      network area density, plate-rod and transverse trabecular distributions with a
      good correlation (r >= 0.85) compared with their micro-CT-derived values. At the
      same time, other measures representing trabecular thickness and separation,
      erosion index, and structure model index produced weak correlations (r < 0.8)
      with their micro-CT-derived values, failing to accurately portray the projected
      trabecular microarchitectural features. Strong correlations of Tb measures
      estimated from two scanners suggest that image data from different scanners can
      be used successfully in multisite and longitudinal studies with linear
      calibration required for some measures. In summary, modern MDCT scanners are
      suitable for effective quantitative imaging of peripheral Tb microarchitecture if
      care is taken to focus on appropriate quantitative metrics.

PMID- 29064580
TI  - Preparation and characterisation of a novel hydrogel based on Auricularia
      polytricha beta-glucan and its bio-release property for vitamin B12 delivery.
AB  - BACKGROUND: This study investigates a novel hydrogel synthesis method and its bio
      release property. This hydrogel, with a three-dimensional network structure based
      on Auricularia polytricha beta-glucan, was characterised by means of Fourier
      transform infrared spectroscopy, 1 H NMR and scanning electron microscopy.
      Vitamin B12 (VB12 , cobalamin) as a hydrophilic functional food component was
      entrapped into these hydrogels. The in vitro release profile of VB12 was
      established in simulated gastric fluid (SGF) and simulated intestinal fluid
      (SIF). RESULTS: The results showed that the hydrogel had medium pore size from 30
      to 300 um, and the swelling ratio increased with the degree of substitution. The
      hydrogel demonstrated good stability in SGF and bio-release capability in SIF for
      VB12 . The accumulated release rate is about 80% in SIF and below 20% in SGF,
      which indicated the significant different release property in stomach and
      intestine. CONCLUSION: The Auricularia polytricha beta-glucan-based hydrogel has
      a good swelling ratio, pepsin stability and pancrelipase-catalysed biodegradation
      property. The bio-release rate is significantly different in SIF and SGF, which
      indicated that this hydrogel could be a good intestinal target carrier of VB12 .
      (c) 2017 Society of Chemical Industry.

PMID- 29064581
TI  - Prospective evaluation of outcome of dogs with intrahepatic portosystemic shunts
      treated via percutaneous transvenous coil embolization.
AB  - OBJECTIVE: To report outcome and complications after percutaneous transvenous
      coil embolization (PTCE) and evaluate the clinical, laboratory, and imaging
      changes in dogs with intrahepatic portosystemic shunts (IHPSS) pre-PTCE and post
      PTCE. STUDY DESIGN: Prospective clinical trial. ANIMALS: Twenty-five dogs (15
      dogs in imaging subgroup) with IHPSS. METHODS: Clinical signs, hematologic, and
      biochemical parameters were recorded before and 3 months after PTCE. All dogs
      received the same medical treatment and underwent PTCE. In the imaging subgroup,
      ultrasonography, hepatic portal scintigraphy, and computed tomography-angiography
      were performed pre-PTCE and post-PTCE. RESULTS: All evaluated bloodwork values
      improved by at least 50% of their initial value, by 3 months post-PTCE. Liver
      volume increased after PTCE (P = .001), but remained lower than normal in 11/15
      dogs. Hepatic arterial fraction decreased after PTCE (P = .029), consistent with
      increased portal blood flow to the liver. Twenty-four of 25 dogs were available
      for reevaluation at 3 months, and all abnormal clinical signs had resolved in
      22/24 dogs. CONCLUSION: PTCE appears promising as a treatment for IHPSS, as
      clinical signs resolved in most cases, bloodwork abnormalities often normalized,
      and the procedure was performed safely with minimal complications. PTCE increased
      hepatic portal perfusion and liver volume in most dogs. These promising results
      justify a future randomized clinical trial comparing PTCE, other attenuation
      options, and medical management alone.

PMID- 29064582
TI  - Establishment of a platform for molecular and immunological characterization of
      the RNA-dependent-RNA-polymerase NS5B of an Egyptian HCV isolate.
AB  - The present work aimed at establishing a platform to enable frequent
      characterization of the HCV RNA-dependent-RNA-polymerase from Egyptian clinical
      isolates. Subjecting amplified HCV-NS5B coding gene from Egyptian patient's serum
      to sequencing, multiple alignment, and phylogenetic analysis confirmed its
      subtype 4a origin. Nucleotide sequence analysis revealed presence of an
      additional start codon at the beginning of the NS5B gene. Peptide sequence
      alignment demonstrated presence of unique amino acid residues in our 4a-NS5B
      sequence distinct from the JFH-1-NS5B sequence as well as unique amino acids
      compared to other genotypes. The distinct molecular structure of the herein
      characterized 4a-NS5B from the 2a-JFH-1-NS5B was further demonstrated both in the
      built 3D models and the Ramachandran plots corresponding to each structure. Both
      the unique amino acid residues and 3D structure of the 4a-NS5B may influence both
      genotype 4a replication rate and response to therapy in comparison to other
      genotypes. Many resistance mutations to polymerase inhibitors were found both in
      ours and other genotypes' sequences. The presence of the required amino acid
      motifs for the RNA dependent RNA polymerase activity encouraged to clone the
      NS5B570-encoding sequence downstream CMV promotor in a mammalian expression
      vector. Such construct was used for both prokaryotic expression in bacteria and
      for DNA immunization. Successful mammalian expression and induction of specific
      immune response were demonstrated by ELISA and Western blotting. The potential of
      both the raised antibodies and the expressed NS5B to differentiate between HCV
      infected and control human sera were demonstrated which reflect their diagnostic
      value.

PMID- 29064583
TI  - Reductions in margin length after excision of grade II mast cell tumors and grade
      I and II soft tissue sarcomas in dogs.
AB  - OBJECTIVE: Quantify changes in the circumferential lengths of surgical margins of
      resected canine mast cell tumors (MCT) and soft tissue sarcomas (STS) between the
      time of collection and histopathology. STUDY DESIGN: Prospective, hypothesis
      driven, clinical study. SAMPLE POPULATION: Two hundred and thirty-seven margins
      from 69 excised tumors (50 MCT and 19 STS) in 51 client-owned dogs. METHODS: The
      lengths of surgical margins were recorded (eg, cranial, caudal, dorsal, and
      ventral) for each tumor at 5 time points: intraoperatively (in vivo), immediately
      after excision (ex vivo), after formalin fixation (postfixation), once mounted on
      glass slides (subgross), and as histologically tumor-free margins (HTFMs).
      RESULTS: Compared to in vivo dimensions, the length of surgical margins at each
      processing step (ie, ex vivo, postfixation, subgross, and HTFM) was reduced by a
      median of 3.0, 5.0, 6.0, and 8.8 mm for MCT; 2.5, 2.0, 5.0, and 5.0 mm for STS.
      All processing steps resulted in significant reductions among MCT samples (P <
      .0001), except between postfixation vs subgross, and for STS samples (P < .0001),
      except between ex vivo vs postfixation and subgross vs HTFM. The maximum
      reduction in the total length of margins (from in vivo to HTFM) was 29.6 and 24.2
      mm for MCT and STS, respectively. CONCLUSION: Surgical margin length reductions
      occur due to a combination of physical factors (eg, tissue elasticity, myofibril
      contraction, and histologic processing) and biological factors (eg, microscopic
      tumor infiltration into the grossly normal surgical margin). CLINICAL
      SIGNIFICANCE: These data provide information relevant to evidence-based surgical
      planning and may influence patient morbidity in the most commonly encountered
      cutaneous malignancies of dogs.

PMID- 29064584
TI  - Accuracy of a patient-specific 3D printed drill guide for placement of cervical
      transpedicular screws.
AB  - OBJECTIVE: To develop a patient-specific 3-dimensional (3D) printed drill guide
      for placement of cervical transpedicular screws and to assess its accuracy. STUDY
      DESIGN: Prospective case-series. SAMPLE POPULATION: Thirty-two cervical pedicle
      screws (CPS) placed in 3 large breed dogs. METHODS: Computed tomographic (CT)
      data of the cervical vertebrae were exported to a medical image processing
      software and 3D virtual vertebral models were created for each vertebra. These
      models were processed in a computer aided design (CAD) software to determine the
      optimal trajectory and size of the CPS. Virtual drill guides were created for
      each patient, 3D-printed, and used intraoperatively. Locking titanium screw heads
      were bonded with polymethylmethacrylate cement to stabilize affected vertebral
      segments. Postoperative CT was used to assess the radiological accuracy of CPS
      placement in each dog. For each screw, CAD files were analyzed to determine a
      screw-diameter-to-pedicle-width-ratio (SDPWR) at the narrowest point of the
      pedicle. RESULTS: A total of 32 CPS were placed, measuring 3.5 mm (n = 20), 2.7
      mm (n = 11), and 2.4 mm (n = 1) in diameter. The majority (29/32) of these screws
      were placed without evidence of vertebral canal breach (grade 0), whereas a
      vertebral canal breach <2 mm (grade 1) was detected in 3/32 screws. This outcome
      was achieved despite a mean SDPWR of 0.75 (range 0.58-0.93). CONCLUSION: The use
      of a 3D-printed patient-specific drill guide permitted accurate placement of 32
      bicortical pedicle screws in the caudal cervical vertebrae of 3 dogs. This
      technique may improve clinical outcome through superior biomechanical properties
      of screws, reduced surgical time, and reduced morbidity. These results warrant
      evaluation of patient outcome in a larger population.

PMID- 29064585
TI  - The dosimetric impact of the prescription isodose line (IDL) on the quality of
      robotic stereotactic radiosurgery (SRS) plans.
AB  - PURPOSE: There is no consensus on the optimal prescription isodose line (IDL) in
      CyberKnife (CK) SRS. We designed a strategy to search for optimal CK plans at
      different levels of IDLs and investigated the dosimetric impact on the quality of
      CK plans. METHODS AND MATERIALS: The retrospective study consisted of 13 CK
      patients with 16 brain tumors. The mean volume and size of the tumors was 9.7 +/-
      10.4 cc and 30.3 +/- 10.9 mm, respectively. Four shells were created at distances
      of 2-3 mm to 60 mm from the target. The constraint dose of the innermost shell
      (D1) was the primary optimization parameter. For isolated brain tumors, D1
      started from the prescription dose and gradually reduced after optimization
      started over. The optimal plans were reached when the coverage started to degrade
      and the desired IDL was achieved. For eight tumors abutting an OAR, both the D1
      and constraint dose to the OAR were gradually pushed until an optimal plan was
      reached for the desired IDL. RESULTS: For the isolated tumors, the V5 Gy, V10 Gy,
      V15 Gy, V20 Gy, and V25 Gy of low IDL (49.6 +/- 2.1%) plans were on average
      23.6%, 28.6%, 33.8%, 26.2%, and 10.6% lower, respectively, comparing to the high
      IDL (88.6 +/- 1.3%) plans. The Conformality Index (CI) of the low IDL plans
      outperformed the high IDL plans (mean: 1.15 vs. 1.24), except for a lesion under
      0.5 cc. The quality of the middle IDL plans (69.6 +/- 1.5%) was close to the low
      IDL plans. Similar results were observed for tumors abutting an OAR. CONCLUSIONS:
      Low IDL plans outperformed high IDL plans for all metrics in tumors > 0.5 cc. The
      lower dose exposure of normal brain tissue and better CI could potentially reduce
      radiation necrosis while the higher maximum dose could improve local control.

PMID- 29064586
TI  - A pivotal role of AMPK signaling in medicarpin-mediated formation of brown and
      beige.
AB  - Obesity poses a substantial threat of a worldwide epidemic and requires better
      understanding of adipose-tissue biology as well as necessitates research into the
      etiology and therapeutic interventions. In this study, Medicarpin (Med), a
      natural pterocarpan, was selected (by screening) as a small-molecule inducer of
      adipocyte differentiation among 854 candidates by using C3H10T1/2 mesenchymal
      stem cell; a cellular model of adipogenesis. Med induced the expression of brown
      adipocyte commitment marker Bmp7 as well as the early regulators of brown fat
      fate Ppargamma, Prdm16, and Pgc-1alpha during differentiation of C3H10T1/2
      mesenchymal stem cells. Med also induced the expression of a key thermogenic
      marker-uncoupling protein 1 (UCP1)-along with expression of other brown-fat
      specific markers and beige-fat-specific markers. Of note, Med significantly
      reduced the expression of white fat markers too. Furthermore, Med treatment
      promoted formation of multilocular lipid droplets (LDs), expression of
      mitochondrial-biogenesis-related genes, and increased oxygen consumption. Gene
      silencing study revealed that Med promotes the development of brown- and beige
      adipocyte characteristics in C3H10T1/2 mesenchymal stem cells through activation
      of the AMPK pathway, and our data allow us to propose Med as a candidate for
      therapeutics against obesity or related metabolic disorders. (c) 2017 BioFactors,
      44(2):168-179, 2018.

PMID- 29064587
TI  - An anergic immune signature in the tumor microenvironment of classical Hodgkin
      lymphoma is associated with inferior outcome.
AB  - OBJECTIVE: The classical Hodgkin lymphoma (cHL) tumor microenvironment shows an
      ongoing inflammatory response consisting of varying degrees of infiltrating
      eosinophils, mast cells, macrophages, regulatory T lymphocytes (Tregs), and
      activated lymphocytes surrounding the malignant cells. Herein, different immune
      signatures are characterized and correlated with treatment outcome. METHODS:
      Tumor-infiltrating leukocytes were phenotyped in biopsies from 459 patients with
      cHL. Time to progression (TTP) (primary progression, relapse, or death from cHL)
      and overall survival were analyzed using Cox proportional hazards regression.
      RESULTS: The leukocyte infiltration in the microenvironment was highly diverse
      between patients and was categorized in 4 immune signatures (active, anergic,
      innate, or mixed). A high proportion of Tregs (anergic) resulted in shorter TTP
      (median 12.9-year follow-up) in age-adjusted analyses (hazard ratio = 1.82; 95%
      confidence interval 1.05-3-15). Epstein-Barr virus (EBV)-positive cases had
      higher proportions of macrophages and activated lymphocytes than EBV negative,
      but neither of those leukocytes predicted prognosis. CONCLUSIONS: Abundant Tregs
      (anergic signature) indicate a shorter TTP, particularly in younger patients.
      This is probably due to a reduced ability of the immune system to attack the
      tumor cells. Our data warrant further investigation if these suggested immune
      signatures could predict outcome of immunotherapy such as immune checkpoint
      inhibitors.

PMID- 29064588
TI  - RECK inhibits cervical cancer cell migration and invasion by promoting p53
      signaling pathway.
AB  - The present study was conducted to investigate the effects of RECK on cervical
      cancer cell migration and invasion to help understand relevant molecular
      mechanisms. QRT-PCR and western blot were respectively utilized to examine the
      transcriptional and translational levels of RECK in cervical cancer cell lines
      (HELA and C33A) and normal cell line (H8). After transfection with RECK
      overexpressing vectors, the expression of RECK mRNA, RECK and p53 signaling
      pathway-related proteins (p21, p53, bcl-2, and Bax) in cervical cancer cells were
      respectively examined using qRT-PCR and western blot. Cervical cancer cell
      migration after transfection was detected by wound healing assay and transwell
      assay. RECK expression was much lower in cervical cancer cell lines compared with
      normal cell line. Results of wound-healing assay results indicated that RECK
      could inhibit cervical cancer cell migration, and transwell assay results
      demonstrated that cell invasion was suppressed by RECK overexpression.
      Furthermore, western blot indicated that the overexpression of RECK could promote
      the activation of p53 signaling pathway by influencing related protein
      expression; whereas its inhibition by PFT-alpha could antagonize the effect of
      RECK on migrative and invasive abilities of cervical cancer cells. RECK could
      inhibit the migration and invasion of cervical cancer cells by activating p53
      signaling pathway.

PMID- 29064589
TI  - Immunodetection of acetylated alpha-tubulin in stony corals: Evidence for the
      existence of flagella in coral male germ cells.
AB  - The molecular and cellular characteristics of male germ cell development remain
      largely unknown in corals. This study focused on the expression pattern of
      acetylated alpha-tubulin (Ac-alpha-Tu), which is involved in male germ cell
      development in various animals across taxa, to gain a better understanding of
      male germ cell development in the stony coral Euphyllia ancora.
      Immunohistochemical analysis of the different stages of male germ cells showed
      the presence of filamentous Ac-alpha-Tu in the early to late stages of male germ
      cells-such as spermatogonia, spermatocytes, and spermatids-as well as in the
      flagella of mature sperm. Immunocytochemical and transmission electron microscope
      analyses demonstrated that early-stage male germ cells possess long flagella
      containing Ac-alpha-Tu. The presence of filamentous Ac-alpha-Tu was also
      immunohistochemically demonstrated in the male germ cells from 14 other coral
      species, implying that possession of flagella with Ac-alpha-Tu is a common
      characteristic of male germ cells in stony corals. Therefore, as a distinctive
      cellular characteristic of male germ cells, Ac-alpha-Tu could be used as a male
      germ cell marker in stony corals; indeed, immunolabeling for Ac-alpha-Tu may be a
      useful method to aid in the identification and morphological observation of male
      germ cells in various corals in basic and applied biology (e.g., aquaculture) as
      well as in ecological studies.

PMID- 29064590
TI  - An Amino-Functionalized Metal-Organic Framework, Based on a Rare Ba12 (COO)18
      (NO3 )2 Cluster, for Efficient C3 /C2 /C1 Separation and Preferential Catalytic
      Performance.
AB  - A barium(II) metal-organic framework (MOF) based on a predesigned amino
      functionalized ligand, namely [Ba2 (L)(DMF)(H2 O)(NO3 )1/3 ]?DMF?EtOH?2 H2 O (UPC
      33) [H3 L=4,4'-((2-amino-5-carboxy-1,3-phenylene)bis(ethyne-2,1-diyl))dibenzoic
      acid] has been synthesized. UPC-33 is a 3-dimensional 3,18-connected network with
      fcu topology with a rare twelve-nuclear Ba12 (COO)18 (NO3 )2 cluster. UPC-33
      shows permanent porosity and a high adsorption heat of CO2 (49.92 kJ mol-1 ),
      which can be used as a platform for selective adsorption of CO2 /CH4 (8.09). In
      addition, UPC-33 exhibits high separation selectivity for C3 light hydrocarbons
      with respect to CH4 (228.34, 151.40 for C3 H6 /CH4 , C3 H8 /CH4 at 273k and 1
      bar), as shown by single component gas sorption and selectivity calculations. Due
      to the existence of -NH2 groups in the channels, UPC-33 can effectively catalyze
      Knoevenagel condensation reactions with high yield, and substrate size and
      electron dependency.

PMID- 29064591
TI  - Self-Assembly through Noncovalent Preorganization of Reactants: Explaining the
      Formation of a Polyfluoroxometalate.
AB  - High-order elementary reactions in homogeneous solutions involving more than two
      molecules are statistically improbable and very slow to proceed. They are not
      generally considered in classical transition-state or collision theories. Yet,
      rather selective, high-yield product formation is common in self-assembly
      processes that require many reaction steps. On the basis of recent observations
      of crystallization as well as reactions in dense phases, it is shown that self
      assembly can occur by preorganization of reactants in a noncovalent
      supramolecular assembly, whereby directing forces can lead to an apparent one
      step transformation of multiple reactants. A simple and general kinetic model for
      multiple reactant transformation in a dense phase that can account for many
      bodied transformations was developed. Furthermore, the self-assembly of
      polyfluoroxometalate anion [H2 F6 NaW18 O56 ]7- from simple tungstate Na2 WO2 F4
      was demonstrated by using 2D 19 F-19 F NOESY, 2D 19 F-19 F COSY NMR spectroscopy,
      a new 2D 19 F{183 W} NMR technique, as well as ESI-MS and diffusion NMR
      spectroscopy, and the crucial involvement of a supramolecular assembly was found.
      The deterministic kinetic reaction model explains the reaction in a dense phase
      and supports the suggested self-assembly mechanism. Reactions in dense phases may
      be of general importance in understanding other self-assembly reactions.

PMID- 29064592
TI  - Pharmaceuticals and pesticides archived on polar passive sampling devices can be
      stable for up to 6 years.
AB  - In the present study, we report the freezer storage stability of pharmaceuticals
      and pesticides for the organic-diffusive gradients in thin-films (o-DGT) passive
      sampler and the polar organic chemical integrative sampler (POCIS). The average
      change on o-DGT after approximately 18 mo was 9 +/- 9% across 30 compounds. For
      POCIS, the average change after approximately 6 yr was 14 +/- 14% for the same
      compounds. Our data suggest that analytes stored on these samplers are stable and
      appropriate for archival purposes. Environ Toxicol Chem 2018;37:762-767. (c) 2017
      SETAC.

PMID- 29064593
TI  - Combination therapy incorporating Bcl-2 inhibition with Venetoclax for the
      treatment of refractory primary plasma cell leukemia with t (11;14).
AB  - Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma
      cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with
      the presence of a chromosome translocation involving the immunoglobulin heavy
      chain (IgH) locus on 14q32, that is t (11;14). Results from early phase clinical
      trials utilizing the selective Bcl-2 inhibitor, venetoclax, as a single agent in
      patients with relapsed MM have had remarkable efficacy among patients with t
      (11;14) abnormality. The present case demonstrates the ability of a combination
      regimen incorporating Bcl-2 inhibition with daratumumab, bortezomib, venetoclax,
      and dexamethasone to induce a rapid and very deep hematologic response in a pPCL
      patient with t (11;14), even in a setting of very refractory disease. This case
      highlights the need to further study Bcl-2 inhibition-based therapy as an option
      for therapy in patients with pPCL with t (11;14).

PMID- 29064594
TI  - Exploration of the expeditious potential of Pseudomonas fluorescens lipase in the
      kinetic resolution of racemic intermediates and its validation through molecular
      docking.
AB  - A profoundly time-efficient chemoenzymatic method for the synthesis of (S)-3-(4
      chlorophenoxy)propan-1,2-diol and (S)-1-chloro-3-(2,5-dichlorophenoxy)propan-2
      ol, two important pharmaceutical intermediates, was successfully developed using
      Pseudomonas fluorescens lipase (PFL). Kinetic resolution was successfully
      achieved using vinyl acetate as acylating agent, toluene/hexane as solvent, and
      reaction temperature of 30 degrees C giving high enantioselectivity and
      conversion. Under optimized condition, PFL demonstrated 50.2% conversion,
      enantiomeric excess of 95.0%, enantioselectivity (E = 153) in an optimum time of
      1 hour and 50.3% conversion, enantiomeric excess of 95.2%, enantioselectivity (E
      = 161) in an optimum time of 3 hours, for the two racemic alcohols, respectively.
      Docking of the R- and S-enantiomers of the intermediates demonstrated stronger H
      bond interaction between the hydroxyl group of the R-enantiomer and the key
      binding residues of the catalytic site of the lipase, while the S-enantiomer
      demonstrated lesser interaction. Thus, docking study complemented the
      experimental outcome that PFL preferentially acylated the R form of the
      intermediates. The present study demonstrates a cost-effective and expeditious
      biocatalytic process that can be applied in the enantiopure synthesis of
      pharmaceutical intermediates and drugs.

PMID- 29064595
TI  - Achieving Amphibious Superprotonic Conductivity in a CuI Metal-Organic Framework
      by Strategic Pyrazinium Salt Impregnation.
AB  - Treatment of a pyrazine (pz)-impregnated CuI metal-organic framework (MOF)
      ([1?pz]) with HCl vapor renders an interstitial pyrazinium chloride salt
      hybridized MOF ([1?pz?6 HCl]) that exhibits proton conductivity over 10-2  S cm-1
      both in anhydrous and under humid conditions. Framework [1?pz?6 HCl] features the
      highest anhydrous proton conductivity among the lesser-known examples of MOF
      based materials exhibiting proton conductivity under both anhydrous and humid
      conditions. Moreover, [1?pz] and corresponding pyrazinium sulfate- and pyrazinium
      phosphate-hybridized MOFs also exhibit superprotonic conductivity over 10-2  S cm
      1 under humid conditions. The impregnated pyrazinium ions play a crucial role in
      protonic conductivity, which occurs through a Grotthuss mechanism.

PMID- 29064596
TI  - A report on the mosquitoes of mainland Aland, southwestern Finland and revised
      list of Finnish mosquitoes.
AB  - To successfully implement surveillance or control strategies for mosquitoes, up
      to-date knowledge of regional species composition is vital. The last report
      regarding mosquitoes (Diptera: Culicidae) in the Aland archipelago, southwestern
      Finland listed 19 species (Utrio, 1979). To determine the current species
      diversity, one collection trip was made to mainland Aland in 2015 and three in
      2016. Mosquitoes (n = 3286) were collected as both adult and immature life stages
      from 88 collections within 29 1-km2 areas. Fifteen of the 19 previously reported
      species were obtained, leaving the current status of four species uncertain. At
      least 11 species previously not reported from Aland, but confirmed on the Finnish
      mainland, were collected. Aedes geminus Peus was identified based on examination
      of the gonostylus, and represents a new species distribution for Finland.
      Anopheles maculipennis s.s. Meigen was confirmed from cytochrome c oxidase
      subunit I (COI) and internal transcribed spacer 2 (ITS2) sequence data and is
      reinstated on the list of Finnish species, along with Ochlerotatus sticticus
      (Meigen). Dahliana geniculata (Olivier) was found in two locations, in 2 months,
      indicating that there is an established population in Aland. The present data
      confirm that at least 27 species inhabit mainland Aland, rising to 31 when
      historical data are included. The Finnish mosquito fauna is increased from 38 to
      41 species.

PMID- 29064597
TI  - miR-23b-3p and miR-125b-5p downregulate apo(a) expression by targeting Ets1 in
      HepG2 cells.
AB  - High concentrations of plasma lipoprotein(a) [Lp(a)] have been inferred to be an
      independent risk factor for cardiovascular and cerebrovascular diseases, such as
      coronary artery diseases, restenosis, and stroke. Apolipoprotein(a) [apo(a)] is
      one of the most important components of Lp(a) and contributes greatly to the
      increased concentration of plasma Lp(a). As a critical positive transacting
      factor of apo(a) gene, Ets1 has been proven as a target gene of several miRNAs,
      such as miR-193b, miR-125b-5p, miR-200b, miR-1, and miR-499. In this study, a
      series of experiments on miRNAs and relative miRNAs inhibitor delivered HepG2
      cells were conducted, and two miRNAs that downregulate the apo(a) by targeting
      the 3'-UTR of Ets1 were identified. Results showed that apo(a) and Ets1 were
      differentially expressed in SMMC7721 and HepG2 cell lines. Meanwhile, apo(a) and
      Ets1 were inversely correlated with several hepatic endogenous miRNAs, such as
      miR-125b-5p, miR-23b-3p, miR-26a-5p, and miR-423-5p, which were predicted to bind
      to Ets1. Results show that miR-125b-5p and miR-23b-3p mimics could inhibit the
      synthesis of apo(a) by directly targeting Ets1 in HepG2, thereby reducing the
      plasma Lp (a) concentration.

PMID- 29064598
TI  - Contribution to mitochondrial research in Brazil: 10th anniversary of the
      mitomeeting.
AB  - This commentary introduces the subject, the context and the history of the
      Brazilian annually held meeting on Mitochondrial Research by the occasion of its
      10th anniversary. Mitomeetings gather people interested in all aspects of
      mitochondrial biology in diverse species, including protists, animals, plants,
      and fungi.

PMID- 29064599
TI  - Spinal Cord Stimulation in Patients With Complex Regional Pain Syndrome: A
      Possible Target for Immunomodulation?
AB  - OBJECTIVE: Complex regional pain syndrome (CRPS) is characterized by continued
      pain disproportional to the inciting event, sensory abnormalities, vasomotor and
      sudomotor disturbances, and motor and trophic changes. Inflammatory involvement
      has been demonstrated in past CRPS studies resulting in pain, swelling, and
      warmth. Currently, it is unknown whether spinal cord stimulation (SCS) has
      immunomodulatory properties. The aim of this study was to determine whether SCS
      has immunomodulatory properties in CRPS patients. METHODS: The primary outcome
      parameters are cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-15, IL
      17, TNF-alpha, IFN-gamma), chemokines (IP-10 and Eotaxin), and growth factors
      (VEGF, PDGFbb, and basic FGF) from interstitial fluid of artificial skin blisters
      before (T0-baseline without SCS) and after SCS therapy (T1-40 Hz standard
      frequency stimulation and T2-preferred frequency stimulation). Secondary outcome
      parameters were baseline demographics, CRPS signs, symptoms, and phenotype
      (inflammatory, vasomotor, dystonia, or neuropathic). Results were analyzed by
      means of a MANOVA repeated measures design. RESULTS: After SCS, the expression of
      both pro- and anti-inflammatory cytokines decreased over time in both the CRPS
      affected extremity and the contralateral extremity. The levels of IP-10, Eotaxin,
      VEGF, and PDGFbb were also significantly reduced bilaterally. There were no
      significant changes in IL-6 and TNF-alpha before and after SCS. The sensory
      signs, symptoms, and phenotype improved after SCS. DISCUSSION: SCS in CRPS
      patients attenuates T-cell activation, improves peripheral tissue oxygenation and
      decreases anti-angiogenetic activity which results in diminished endothelial
      dysfunction and improved bloodflow. The possible immunomodulatory effects of SCS
      opens new therapeutic possibilities in diseases with the involvement of the
      immune system and vasomotor disturbances, and requires further research on these
      mechanisms of action.

PMID- 29064601
TI  - Differential involvement of nigral subregions in idiopathic parkinson's disease.
AB  - In this study, the prevalence of abnormality in putative nigrosome 1 and
      nigrosome 4 (N1 and N4, respectively) was investigated in early versus late-stage
      idiopathic Parkinson's disease (IPD) patients. A total of 128 IPD patients (early
      stage[n = 89]; late stage[n = 39]) and 15 healthy subjects were scanned for high
      resolution (0.5 * 0.5 * 1.0 mm3 ) multiecho gradient-recalled echo MRI and
      dopamine transporter PET imaging. The MRI data were processed for susceptibility
      map-weighted imaging (SMWI) to improve a contrast-to-noise ratio, and the images
      were resliced at 0.5 mm to define N1 and N4. When each side of N1 and N4 was
      assessed separately for the loss of hyperintensity by two independent reviewers,
      the consensus review results showed that in early-stage IPD (178 substantia
      nigras [SNs]), the loss of hyperintensity was observed more often in only the N1
      region (65.2%) when compared to in both N1 and N4 regions (34.8%). In late-stage
      IPD (78 SNs), on the other hand, the loss in only the N1 region (25.6%) was less
      prevalent than in both N1 and N4 (74.4%) (P < 0.0001). Additionally, intact SNs
      (both in N1 and N4) were observed 17 SNs (9.6%) of the early-stage IPD patients,
      whereas it was not found in any SNs of the late-stage IPD patients (P = 0.005).
      Moreover, involvement of both N1 and N4 on both sides was found in 19.1% of the
      early-stage IPD patients, whereas its incidence was higher (61.5%) in the late
      stage IPD patients (P < 0.0001), suggesting that the loss of hyperintensity in
      IPD progresses from N1 to N4 as the disease advances. Hum Brain Mapp 39:542-553,
      2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29064600
TI  - Propensity for cis-Proline Formation in Unfolded Proteins.
AB  - In unfolded proteins, peptide bonds involving Pro residues exist in equilibrium
      between the minor cis and major trans conformations. Folded proteins
      predominantly contain trans-Pro bonds, and slow cis-trans Pro isomerization in
      the unfolded state is often found to be a rate-limiting step in protein folding.
      Moreover, kinases and phosphatases that act upon Ser/Thr-Pro motifs exhibit
      preferential recognition of either the cis- or trans-Pro conformer. Here, NMR
      spectra obtained at both atmospheric and high pressures indicate that the
      population of cis-Pro falls well below previous estimates, an effect attributed
      to the use of short peptides with charged termini in most prior model studies.
      For the intrinsically disordered protein alpha-synuclein, cis-Pro populations at
      all of its five X-Pro bonds are less than 5 %, with only modest ionic strength
      dependence and no detectable effect of the previously demonstrated interaction
      between the N- and C-terminal halves of the protein. Comparison to small peptides
      with the same amino-acid sequence indicates that peptides, particularly those
      with unblocked, oppositely charged amino and carboxyl end groups, strongly
      overestimate the amount of cis-Pro.

PMID- 29064602
TI  - Brain stimulation-induced neuroplasticity underlying therapeutic response in
      phantom sounds.
AB  - Noninvasive brain stimulation can modify phantom sounds for longer periods by
      modulating neural activity and putatively inducing regional neuroplastic changes.
      However, treatment response is limited and there are no good demographic or
      clinical predictors for treatment outcome. We used state-of-the-art voxel-based
      morphometry (VBM) to investigate whether transcranial magnetic stimulation
      induced neuroplasticity determines therapeutic outcome. Sixty subjects
      chronically experiencing phantom sounds (i.e., tinnitus) received repetitive
      transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and
      temporal cortex according to a protocol that has been shown to yield a
      significantly higher number of treatment responders than sham stimulation and
      previous stimulation protocols. Structural magnetic resonance imaging was
      performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE
      corrected), we assessed longitudinal gray matter changes as well as structural
      connectivity between the ensuing regions. We observed longitudinal mesoscopic
      gray matter changes of left dorsolateral prefontal (DLPFC), left operculo
      insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not
      nonresponders (N = 38), as indicated by a group * time interaction and post-hoc
      tests. These results were neither influenced by age, sex, hearing loss nor by
      tinnitus laterality, duration, and severity at baseline. Furthermore, we found
      robust DLPFC-insula and insula-ITC connectivity in responders, while only
      relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be
      demonstrated in nonresponders. Our results reinforce the implication of
      nonauditory brain regions in phantom sounds and suggest the dependence of
      therapeutic response on their neuroplastic capabilities. The latter in turn may
      depend on (differences in) their individual structural connectivity. Hum Brain
      Mapp 39:554-562, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29064603
TI  - Histone deacetylase inhibitor stimulates E2 and P4 secretion in sika deer ovarian
      granulosa cells at a moderate dose.
AB  - The histone deacetylase inhibitor (HDACi) and tumor suppressor play an important
      role in genome reorganization and epigenetic regulation. In this study, granulosa
      cells (GCs) isolated from sika deer ovaries were cultured and treated with
      different concentrations of trichostatin A (TSA) for 48 h. It was found that TSA
      inhibited GCs proliferation and induced GCs apoptosis by upregulating expression
      of BAX, meanwhile, downregulating expression of GLUT3, GLUT8, BCL-XL. In
      addition, TSA caused cell cycle arrest at the G1 and G2/M phase accompanied by
      reducing expression of Cyclin D2 and CDK4. TSA pretreatment increased DNMT3a,
      DNMT1, HDAC1, and HAT1 expression, and attenuated them when TAS higher than 50
      nM. The protein levels of H3K9ac and H4K8ac in GCs were increased at 48 h after
      TSA treatment. TSA stimulated the secretion of estradiol and progesterone at a
      moderate dose. Our data suggest that TSA is important as a regulator of steroid
      hormone synthesis in granulosa cells during follicular development in the sika
      deer ovary.

PMID- 29064604
TI  - Changes of Metabolic Disorders Associated Peripheral Cytokine/Adipokine Traffic
      in Non-Obese Chronic Back Patients Responsive to Burst Spinal Cord Stimulation.
AB  - OBJECTIVES: In our previous study, anti-inflammatory IL-10 serum levels were
      significantly elevated after burst spinal cord stimulation (SCS) in back pain
      patients and correlated with pain intensity. This current study extended cytokine
      analysis including metabolic-associated adipokine/cytokine serum assessment in
      chronic back pain patients with co-existing metabolic disorders such as diabetes,
      hypertension, and cardiovascular diseases. METHODS: At baseline and after three
      months of burst SCS treatment, leptin (LP), adiponectin (AN), and ghrelin (GH)
      were recorded in non-/pre-obese chronic back pain patients with co-existing
      metabolic disorders and compared to age-/gender-matched healthy controls (HC).
      RESULTS: Mean BMI was 22 +/- 0.81 kg/m2 in 12 (five male/seven female)
      participants with diabetes in 6/12 (50%), hypertension in 9 (75%), and CVD in
      five patients (42%). Pre- and post-SCS LP levels were significantly higher
      compared to healthy controls: pre-SCS, 30567 (12,996-58,821) vs. HC, 7952 (4932
      12,583) pg/mL, p = 0.029; post-SCS, 18,890 (7140-44,719) vs. HC, 7952 (4932
      12,583) pg/mL, p = 0.035. Pre- and post-SCS changes of GH (p = 0.18) and AN (p =
      0.8) did not differ significantly. GH serum levels correlated with AN (Spearman r
      = 0.5; p = 0.012; 95 CI 0.11 to -0.76) and AN levels were significantly
      correlated with higher age (Pearson correlation r = 0.8; p = 0.002; 95 CI 0.41
      0.94) at baseline. CONCLUSIONS: This study determined serum changes of metabolic
      associated cytokines/adipokines in non-obese chronic back pain patients
      responsive to burst SCS suggesting that neuroinflammation assessment may consider
      pain-associated mood, cognition, sleep, and metabolic state.

PMID- 29064606
TI  - Long-Term Stability of Short Circuits in Deep Brain Stimulation.
AB  - OBJECTIVES: To evaluate the long-term course of DBS electrodes with short
      circuited contacts. MATERIALS AND METHODS: Electrodes with bipolar impedances
      below 150 Omega were identified from a cohort of 1044 patients with 2082
      electrodes for variable movement disorders. The long-term course was analyzed
      from follow-up data. RESULTS: Short circuits were found in 62 electrodes (3.0%)
      from 60 patients (5.7%). They were restricted to two contacts in 57 electrodes
      (91.9%) and included more than two contacts in five electrodes. Onset was related
      to surgery (implantation, impulse generator replacements, or other surgical
      revisions) in 42 electrodes (67.7%). The onset was undetermined in 11 electrodes.
      In eight electrodes (12.9%) with previously normal impedances, the short circuit
      occurred spontaneously during long-term DBS and in one electrode after a fall.
      Repeated impedance checks at follow-ups of >=3 months were available in 41
      electrodes with short circuits. Twenty-six electrodes (63.4%) showed stable low
      impedances during observation up to nine years and two months (median 29 months).
      In four electrodes low impedances were stable until surgical revisions. In eight
      electrodes (19.5%) with observation up to nine years and seven months (median 54
      months), short circuits were only detected intermittently but remained restricted
      to two contacts. In three electrodes (7.3%) intermittent short circuits between
      more than two contacts were found during long-term DBS. CONCLUSIONS: An
      increasing cumulative incidence demonstrates the clinical importance of short
      circuits. In the majority of electrodes, short circuits are restricted and remain
      restricted to two contacts during long-term stimulation.

PMID- 29064607
TI  - Hypothalamic-pituitary-thyroid (HPT) axis functioning in anxiety disorders. A
      systematic review.
AB  - Depression has repeatedly been linked to subclinical hypothyroidism, and thyroid
      hormones have successfully been used to augment antidepressant treatment. By
      contrast, the extent of thyroid dysfunction in anxiety disorders remains less
      clear. This is surprising, given that anxiety-related symptoms (e.g.,
      nervousness, palpitations, increased perspiration) are highly prevalent in
      hyperthyroidism. The present study was undertaken to synthesize the literature on
      hypothalamic-pituitary-thyroid (HPT) axis functioning in anxiety disorders. The
      PubMed and PsycINFO databases were systematically searched. Three types of
      studies were included: (1) "comorbidity studies" assessing the prevalence of
      thyroid disorders in individuals with anxiety disorders, (2) "case-control
      studies" comparing HPT parameters between patients and controls, and (3)
      "correlational studies" assessing self-reported anxiety levels and HPT
      parameters. Risk of bias was assessed via a standardized quality rating. Twenty
      studies were eligible. Nearly all found the comorbidity between anxiety and
      thyroid disorders was significant. Half of the studies additionally supported the
      notion of subtle thyroid dysfunction in that thyroid-stimulating hormone (TSH)
      responses to the administration of thyrotropin-releasing hormone (TRH) were
      blunted and an inverse relationship was observed between self-reported anxiety
      levels and TSH. Overall, HPT assessments were well conducted, but several studies
      failed to adjust their analyses for smoking, body mass index (BMI), and
      depression. The findings resonate well with clinical recommendations to routinely
      screen for thyroid disorders in patients with anxiety disorders, and with what is
      known from basic research about thyroid-brain interactions. The results of the
      risk of bias assessment underscore the importance of further high-quality
      experimental and longitudinal epidemiological research.

PMID- 29064608
TI  - Diffuse brain damage in normal tension glaucoma.
AB  - Brain changes within and beyond the visual system have been demonstrated in
      primary open angle glaucoma (POAG), the most common type of glaucoma. These
      changes have been often interpreted as a neurodegenerative process due, at least
      partially, to the raised intraocular pressure (IOP). In this context, normal
      tension glaucoma (NTG), a form of POAG with IOP <21 mm Hg despite the typical
      glaucomatous findings, represents the most suitable model of glaucoma to test the
      validity of this hypothesis. We acquired multimodal brain MRI in NTG patients (n
      = 17) and compared them with demographically matched groups of POAG patients with
      raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was
      performed with nonparametric permutation testing. Both NTG and POAG patients
      showed, compared to NC, significantly more gray matter atrophy in both the visual
      system and in nonvisual brain regions and altered diffusion tensor imaging
      derived anatomical connectivity (AC; lower fractional anisotropy and/or higher
      diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and
      higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with
      respect to NC was altered in NTG at short-range level [visual network (VN),
      ventral attention network] and in POAG at long-range level (between secondary VN
      and limbic network). FC of POAG was higher than NTG in both VN and executive
      network. This study provides further evidence that diffuse structural and
      functional abnormalities across glaucoma brain may be, at least partially,
      independent of raised IOP and the consequent retinal degeneration. This further
      defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp
      39:532-541, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29064609
TI  - The micronome of mesenchymal stromal cells is partially responsive to
      inflammation.
AB  - Mesenchymal stromal cells (MSCs) display a special immunological profile that
      allows their potential use as immunotherapeutic cells. Nowadays, foreskin (FSK)
      represents a valuable reservoir of MSCs with International Society for Cellular
      Therapy (ISCT) compliant criteria and relevant functional properties. However,
      their mode of action is poorly understood and needs to be more elucidated to
      optimize their therapeutic use. Because microRNAs (miRNAs) act as key regulators
      in a wide variety of biological processes, we decided to establish the micronome
      of FSK-MSCs, the influence of inflammation and the predicted target pathways.
      Here, we provide the full list of unchanged and additional four differentially
      expressed miRNAs, miR-199b, -296-3p and -589-5p being downregulated whilst miR
      146-3p being upregulated, in MSCs following their exposure to a cocktail of
      proinflammatory cytokines. MicroRNA target prediction in addition to Pathway
      enrichment analysis performed using miRNet, showed that miR-296-3p is linked to
      antigen processing and presentation pathway. Collectively, our data indicate that
      the micronome of FSK-MSCs is partially responsive to inflammation. Differentially
      expressed miRNAs are subsequently modulated by inflammation and seem to be
      involved in regulating the immunological fate of FSK-MSCs. These miRNAs deserve
      more attention in order to optimize MSC-based therapy and achieve the appropriate
      therapeutic effect.

PMID- 29064610
TI  - Small incision cataract surgery provided by a regional population in the Pacific:
      a 12-month follow-up.

PMID- 29064612
TI  - Wavelength-Gated Dynamic Covalent Chemistry.
AB  - Chemical reactions are classically controlled by the judicious choice of
      functional groups as well as external factors such as temperature and catalysts.
      However, the use of light-induced reactions not only offers precise temporal and
      spatial control, but critically allows highly specific reaction channels to be
      selectively addressed through wavelength and intensity, thereby enabling targeted
      covalent bonds to be made and broken. Photoreversible cycloadditions are the most
      promising candidates to seize the outlined potential upon selective cyclization
      and cycloreversion, but are today still far from fulfilling these expectations.
      The current Minireview critically explores the current challenges in the
      application of photoreversible cycloadditions and discusses the steps necessary
      to realize their potential in molecular biology, biomimetic systems, 3D laser
      lithographic processes, and advanced soft matter materials with reprogrammable
      and self-healing properties.

PMID- 29064611
TI  - Understanding suicide risk within the Research Domain Criteria (RDoC) framework:
      A meta-analytic review.
AB  - BACKGROUND: The field is in need of novel and transdiagnostic risk factors for
      suicide. The National Institute of Mental Health's Research Domain Criteria
      (RDoC) provides a framework that may help advance research on suicidal behavior.
      METHOD: We conducted a meta-analytic review of existing prospective risk and
      protective factors for suicidal thoughts and behaviors (ideation, attempts, and
      deaths) that fall within one of the five RDoC domains or relate to a prominent
      suicide theory. Predictors were selected from a database of 4,082 prospective
      risk and protective factors for suicide outcomes. RESULTS: A total of 460
      predictors met inclusion criteria for this meta-analytic review and most examined
      risk (vs. protective) factors for suicidal thoughts and behaviors. The overall
      effect of risk factors was statistically significant, but relatively small, in
      predicting suicide ideation (weighted mean odds ratio: wOR = 1.72; 95% CI: 1.59
      1.87), suicide attempt (wOR = 1.66 [1.57-1.76), and suicide death (wOR = 1.41
      [1.24-1.60]). Across all suicide outcomes, most risk factors related to the
      Negative Valence Systems domain, although effect sizes were of similar magnitude
      across RDoC domains. CONCLUSIONS: This study demonstrated that the RDoC framework
      provides a novel and promising approach to suicide research; however, relatively
      few studies of suicidal behavior fit within this framework. Future studies must
      go beyond the "usual suspects" of suicide risk factors (e.g., mental disorders,
      sociodemographics) to understand the processes that combine to lead to this
      deadly outcome.

PMID- 29064613
TI  - Everolimus-associated perianal ulcers in an eight-month-old heart transplant
      recipient.
AB  - mTOR inhibitors have a wide spectrum of therapeutic applications in adults and
      children. Little is known, however, about serious adverse effects in children
      undergoing mTOR inhibitor therapy. Oral ulcers are common and sometimes severe,
      but no other gastrointestinal involvement has been reported so far. Here we
      present a case of everolimus-associated perianal ulcers in an eight-month-old
      infant, 3 months after heart transplantation, which necessitated the drug's
      discontinuation. In a thorough series of diagnostic tests, we identified no other
      cause for the progressive perianal ulceration. The recognition and appropriate
      management of mTOR inhibitors' adverse effects in pediatric patients are
      essential and remain challenging.

PMID- 29064614
TI  - Accuracy of the pacemaker event recorder versus Holter-ECG to detect both
      symptomatic and asymptomatic ventricular arrhythmias.
AB  - BACKGROUND: Although new pacemakers can register cardiac rhythm, few studies were
      performed evaluating their accuracy in diagnosing ventricular arrhythmias (VA).
      This study aimed to assess the correlation and agreement between the pacemaker's
      monitor and the ambulatory Holter in detecting VA. METHODS AND RESULTS: We
      studied 129 patients with pacemakers, mean age 68.6 +/- 19.1 years, 54.8% female.
      Once Holter monitoring was connected, the pacemakers' event counters were reset
      and clocks of both systems were synchronized to register electrocardiograms (ECG)
      simultaneously. Pacemakers were programmed to detect the lowest ventricular rate
      and lowest number of sequential beats allowed in their event monitors. After 72
      hours, Holter and pacemakers records were analyzed. VA was defined in Holter and
      event monitor, respectively, as: isolated premature ventricular complexes: "PVC";
      pairs: "couplets"; nonsustained ventricular tachycardia (NSVT): "triplets"-3
      beats; "runs"-4-8 or > 8 beats, and high ventricular rates ("HVR")-3-4 beats.
      Spearman correlations evaluated whether pacemaker and Holter identified the same
      parameters. Intraclass correlation coefficients (ICCs) and respective 95%
      confidence intervals were calculated to assess the concordance between methods.
      The agreement between both systems was low, except for "triplet" and three beats
      NSVT (ICC = 0.984). The correlation for more than 10 PVC/h was moderate (Kappa =
      0.483). When the pacemaker was programmed to detect HVR sequences of three beats
      lower than 140 bpm (< 140/3), the correlation with NSVT was perfect (r = 1) and
      agreement was also quite high (ICC = 0.800). CONCLUSIONS: Pacemakers' event
      monitors underestimate the occurrence of ventricular arrhythmias detected by
      Holter. Standardization of pacemakers' algorithms is required before using this
      function for patients' clinical follow-up.

PMID- 29064615
TI  - Evaluation of a microfluidic flow assay to screen for von Willebrand disease and
      low von Willebrand factor levels.
AB  - : Essentials von Willebrand factor (VWF) function is shear stress dependent.
      Platelet accumulation in a microfluidic assay correlates with VWF levels. The
      microfluidic assay discriminates type 1 von Willebrand disease from healthy
      controls. The microfluidic flow assay detects responses to therapeutic
      intervention (DDAVP). SUMMARY: Background von Willebrand disease (VWD) is a
      mucocutaneous bleeding disorder with a reported prevalence of 1 in 10 000. von
      Willebrand factor (VWF) function and platelet adhesion are regulated by
      hemodynamic forces that are not integrated into most current clinical assays.
      Objective We evaluated whether a custom microfluidic flow assay (MFA) can screen
      for deficiencies in VWF in patients presenting with mucocutaneous bleeding.
      Methods Whole blood from individuals with mucocutaneous bleeding was assayed in a
      custom MFA. Results Thirty-two patients with type 1 VWD (10/32) or reported
      mucocutaneous bleeding were enrolled. The platelet adhesion velocity (r = 0.5978
      for 750 s-1 and 0.6895 for 1500 s-1 ) and the maximum platelet surface area
      coverage (r = 0.5719 for 750 s-1 and 0.6633 for 1500 s-1 ) in the MFA correlated
      with VWF levels. Furthermore, the platelet adhesion velocity at 750 s-1 (type 1
      VWD, mean 0.0009761, 95% confidence interval [CI] 0.0003404-0.001612; control,
      mean 0.003587, 95% CI 0.002455-0.004719) and at 1500 s-1 (type 1 VWD, mean
      0.0003585, 95% CI 0.00003914-0.0006778; control, mean 0.003132, 95% CI 0.001565
      0.004699) differentiated type 1 VWD from controls. Maximum platelet surface area
      coverage at 750 s-1 (type 1 VWD, mean 0.1831, 95% CI 0.03816-0.3281; control,
      mean 0.6755, 95% CI 0.471-0.88) and at 1500 s-1 (type 1 VWD, mean 0.07873, 95% CI
      0.01689-0.1406; control, mean 0.6432, 95% CI 0.3607-0.9257) also differentiated
      type 1 VWD from controls. We also observed an improvement in platelet
      accumulation after 1-desamino-8-d-arginine vasopressin (DDAVP) treatment at 1500
      s-1 (pre-DDAVP, mean 0.4784, 95% CI 0.1777-0.7791; post-DDAVP, mean 0.8444, 95%
      CI 0.7162-0.9726). Conclusions These data suggest that this approach can be used
      as a screening tool for VWD.

PMID- 29064616
TI  - Gain-of-function HCN2 variants in genetic epilepsy.
AB  - Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses
      seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker
      hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered
      integral to SWD genesis, making them an ideal gene candidate for GGE. We
      identified HCN2 missense variants from a large cohort of 585 GGE patients,
      recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional
      analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The
      p.S632W variant was identified in a patient with idiopathic photosensitive
      occipital epilepsy and segregated in the family. This variant was also
      independently identified in an unrelated patient with childhood absence seizures
      from a European cohort of 238 familial GGE cases. The p.V246M variant was
      identified in a patient with photo-sensitive GGE and his father diagnosed with
      juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and
      p.V246M had an identical functional impact including a depolarizing shift in the
      voltage dependence of activation that is consistent with a gain-of-function. In
      contrast, no biophysical changes resulted from the introduction of common
      population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that
      did not segregate with disease. Our data suggest that HCN2 variants can confer
      susceptibility to GGE via a gain-of-function mechanism.

PMID- 29064617
TI  - Social comparison in the brain: A coordinate-based meta-analysis of functional
      brain imaging studies on the downward and upward comparisons.
AB  - Social comparison is ubiquitous across human societies with dramatic influence on
      people's well-being and decision making. Downward comparison (comparing to worse
      off others) and upward comparison (comparing to better-off others) constitute two
      types of social comparisons that produce different neuropsychological
      consequences. Based on studies exploring neural signatures associated with
      downward and upward comparisons, the current study utilized a coordinate-based
      meta-analysis to provide a refinement of understanding about the underlying
      neural architecture of social comparison. We identified consistent involvement of
      the ventral striatum and ventromedial prefrontal cortex in downward comparison
      and consistent involvement of the anterior insula and dorsal anterior cingulate
      cortex in upward comparison. These findings fit well with the "common-currency"
      hypothesis that neural representations of social gain or loss resemble those for
      non-social reward or loss processing. Accordingly, we discussed our findings in
      the framework of general reinforcement learning (RL) hypothesis, arguing how
      social gain/loss induced by social comparisons could be encoded by the brain as a
      domain-general signal (i.e., prediction errors) serving to adjust people's
      decisions in social settings. Although the RL account may serve as a heuristic
      framework for the future research, other plausible accounts on the
      neuropsychological mechanism of social comparison were also acknowledged. Hum
      Brain Mapp 39:440-458, 2018. (c) 2017 Wiley Periodicals, Inc.

PMID- 29064619
TI  - External validation of the PLASMIC score: a clinical prediction tool for
      thrombotic thrombocytopenic purpura diagnosis and treatment.
AB  - : Essentials Severe ADAMTS-13 deficiency is key to thrombotic thrombocytopenic
      purpura (TTP) diagnosis. PLASMIC score predicts ADAMTS-13 deficiency in suspected
      TTP with high discrimination. PLASMIC score is more generalizable with fewer
      missing data than alternative clinical scores. PLASMIC score identifies a
      subgroup of patients lacking significant response to plasma exchange. SUMMARY:
      Background The PLASMIC score was recently published to distinguish patients with
      severe ADAMTS-13 deficiency from those without for early identification of
      thrombotic thrombocytopenia purpura (TTP). Objective We performed an independent
      external validation of the PLASMIC score for clinical prediction of severe ADAMTS
      13 deficiency. Patients/Methods We studied an independent cohort of 112
      consecutive hospitalized patients with suspected thrombotic microangiopathy and
      appropriate ADAMTS-13 testing (including 21 patients with TTP diagnosis). Results
      The PLASMIC score model predicted severe ADAMTS-13 deficiency with a c statistic
      of 0.94 (0.88-0.98). When dichotomized at high (score 6-7) vs. low-intermediate
      risk (score 0-5), the model predicted severe ADAMTS-13 deficiency with positive
      predictive value of 72%, negative predictive value of 98%, sensitivity of 90% and
      specificity of 92%. In the low-intermediate risk group (score 0-5) there was no
      significant improvement in overall survival associated with plasma exchange.
      Conclusions The PLASMIC score model had excellent applicability, discrimination
      and calibration for predicting severe ADAMTS-13 deficiency. The clinical
      algorithm allowed identification of a subgroup of patients who lacked a
      significant response to empiric treatment.

PMID- 29064620
TI  - Intrathecal Drug Delivery Systems for the Management of Chronic Noncancer Pain: A
      Systematic Review of Economic Evaluations.
AB  - BACKGROUND: Intrathecal drug delivery (ITDD) systems are one of a limited number
      of management options for chronic noncancer pain, cancer pain, and spasticity.
      Concerns over their effectiveness and high initial costs led National Health
      Service (NHS) England to decommission ITDD for patients with chronic noncancer
      pain. However, the extent to which this decision is in line with existing
      economic evidence is unclear. The aim of this systematic review was to identify
      and review the existing evidence on the cost effectiveness of ITDD for chronic
      noncancer pain. METHODS: Full and partial economic evaluations on ITDD were
      identified through systematic searches in MEDLINE, Embase, Web of Science, and
      the NHS for Reviews and Dissemination databases. Database searches were
      complemented by hand searching of reference lists of relevant studies and
      searches of grey literature. Study selection was carried out by 2 assessors,
      independently. Study quality assessment was performed to inform critical
      appraisal of health economics studies. Data were extracted using a data
      extraction form developed for the purposes of this study. RESULTS: Four thousand
      four hundred and sixty-four unique studies were identified, of which 7 met the
      inclusion criteria. With the exception of 1 study, the studies found ITDD to be
      either cost saving or cost effective compared to conventional medical management.
      ITDD became cost ineffective in 1 further study following price year adjustment
      to 2016. CONCLUSIONS: Study findings showed ITDD to be not cost effective only in
      extremely conservative scenarios. There is limited evidence on the effectiveness
      of ITDD in noncancer pain; however, the available economic evidence controverts
      arguments to refute the treatment on economic grounds.

PMID- 29064621
TI  - Synthesis, biological evaluation and SAR analysis of novel poly-heterocyclic
      compounds containing pyridylpyrazole group.
AB  - BACKGROUND: In recent years, pyridylpyrazole derivatives, such as pyridylpyrazole
      containing anthranilic diamide have attracted much attention by virtue of their
      useful insecticidal properties and unique action mode. Moreover, some
      pyridylpyrazole-containing compounds have also been found to possess significant
      fungicidal activities. With the aim of discovering new bioactive agrochemicals
      for crop protection, a series of poly-heterocyclic compounds containing
      pyridylpyrazole and aziridine, or beta-lactam, or thiazolinone moieties were
      synthesized. RESULTS: A series of pyridylpyrazole-containing poly-heterocyclic
      compounds were obtained, and confirmed through IR, 1 H NMR, 13 C NMR, HRMS and
      elemental analysis. The crystalline structure of 4-(3-bromo-1-(3-chloropyridin-2
      yl)-1H-pyrazol-5-yl)-3-chloro-1-mesitylazetidin-2-one (compound 13f) was
      determined to further illustrate a trans- configuration of the beta-lactam motif.
      In addition, bioassays showed that most of these new compounds exhibited modest
      insecticidal activity towards Mythimna separate Walker at 200 ug mL-1 . Some of
      the compounds displayed excellent fungicidal activity towards some plant fungi,
      including Cercospora arachidicola (13j: EC50 = 14.5 ug mL-1 ), Physalospora
      piricola (12d and 13d: EC50 = 10.5 and 9.70 ug mL-1 ), Alternaria solani Sorauer
      (13j: EC50 = 7.29 ug mL-1 ), Puccinia sorghi Schw. (13d: control efficacy 99.0 +/
      2.1% at 200 ug mL-1 ) and Erysiphe graminis (14d: control efficacy 95.0 +/- 1.4%
      at 200 ug mL-1 ). CONCLUSION: Compounds 12b-12e, 13a, 13d, 13f, 13j, 13 k and 14d
      could be considered potential fungicidal lead compounds to do further structural
      optimization. The structure-activity relationship analysis in this study brings
      some new understanding to the biological activities of N-pyridylpyrazole
      containing compounds, and provides important information for the research and
      development of novel agricultural fungicides with poly-heterocyclic structures.
      (c) 2017 Society of Chemical Industry.

PMID- 29064622
TI  - Allelopathic Activity and Chemical Composition of Rhynchosia minima (L.) DC.
      Essential Oil from Egypt.
AB  - Aromatic plants attract the attention of many researchers worldwide due to their
      worthy applications in agriculture, human prosperity, and the environment.
      Essential oil (EO) could be exploited as effective alternatives to synthetic
      compounds as it has several biological activities including allelopathy. The EO
      from the aerial parts of Rhynchosia minima was extracted by hydrodistillation and
      investigated by gas chromatography/mass spectrometry (GC/MS). Different
      concentrations (50, 100, 150 and 200 MUL L-1 ) of the EO were prepared for
      investigation of their allelopathic potential on two weeds; Dactyloctenium
      aegyptium and Rumex dentatus. Twenty-eight compounds, mainly sesquiterpenes
      (69.13%) were determined. The major compounds are alpha-eudesmol, 2-allyl-5-tert
      butylhydroquinone, caryophyllene oxide, trans-caryophyllene, and tau-cadinol. The
      EO from the R. minima showed a significant inhibition of D. aegyptium and R.
      dentatus germination, while the seedling growth was stimulated. Therefore, it is
      not recommended to treat these noxious weeds with the EO of R. minima before the
      germination. In contrast, the apparent stimulatory effect on the seedling growth
      offers further studies to use the EO of R. minima to enhance the fitness of
      different economic crops. However, characterization of green bio-herbicides such
      as EO (allelochemicals) from wild plants raises a new opportunity for the
      incorporation of new technology of bio-control against the noxious weeds.

PMID- 29064623
TI  - Experimental design matters for statistical analysis: how to handle blocking.
AB  - BACKGROUND: Nowadays, evaluation of the effects of pesticides often relies on
      experimental designs that involve multiple concentrations of the pesticide of
      interest or multiple pesticides at specific comparable concentrations and,
      possibly, secondary factors of interest. Unfortunately, the experimental design
      is often more or less neglected when analysing data. Two data examples were
      analysed using different modelling strategies. First, in a randomized complete
      block design, mean heights of maize treated with a herbicide and one of several
      adjuvants were compared. Second, translocation of an insecticide applied to maize
      as a seed treatment was evaluated using incomplete data from an unbalanced design
      with several layers of hierarchical sampling. Extensive simulations were carried
      out to further substantiate the effects of different modelling strategies.
      RESULTS: It was shown that results from suboptimal approaches (two-sample t-tests
      and ordinary ANOVA assuming independent observations) may be both quantitatively
      and qualitatively different from the results obtained using an appropriate linear
      mixed model. The simulations demonstrated that the different approaches may lead
      to differences in coverage percentages of confidence intervals and type 1 error
      rates, confirming that misleading conclusions can easily happen when an
      inappropriate statistical approach is chosen. CONCLUSION: To ensure that
      experimental data are summarized appropriately, avoiding misleading conclusions,
      the experimental design should duly be reflected in the choice of statistical
      approaches and models. We recommend that author guidelines should explicitly
      point out that authors need to indicate how the statistical analysis reflects the
      experimental design. (c) 2017 Society of Chemical Industry.

PMID- 29064625
TI  - Coincidence.

PMID- 29064624
TI  - Toxicity to and egg-laying avoidance of Drosophila suzukii (Diptera:
      Drosophilidae) caused by an old alternative inorganic insecticide preparation.
AB  - BACKGROUND: The application of synthetic insecticides remains the most used tool
      for the management of spotted-wing drosophila, Drosophila suzukii (Matsumura)
      (Diptera: Drosophilidae). However, management of this pest in the organic
      production of soft-skinned fruits is a complex task due to the restricted number
      of registered products. Here, we assess the toxicity of lime sulfur and evaluate
      whether lime sulfur-treated strawberry plants affected the oviposition and
      development of D. suzukii. RESULTS: Lime sulfur exhibited adequate toxicity to D.
      suzukii (LC50 = 26.6 mL L-1 ) without phytotoxicity to strawberry plants. When D.
      suzukii females were exposed to lime sulfur-treated plants in no-choice
      bioassays, oviposition was significantly (t-test, P < 0.05) reduced compared with
      that on untreated plants. In free-choice bioassays, D. suzukii females laid
      significantly (paired t-test, P < 0.05) more eggs on untreated plants.
      Furthermore, in the free-choice bioassays, immature development was slower for
      adults that originated from eggs laid on lime sulfur-treated plants than from
      those laid on untreated plants. CONCLUSIONS: Lime sulfur showed adequate control
      and, therefore, has potential for use as a management tool against D. suzukii
      infestations in organic production systems. This old, alternative insecticide
      preparation not only caused adult fly mortality, but also reduced the number of
      eggs laid on lime sulfur-treated plants. (c) 2017 Society of Chemical Industry.

PMID- 29064627
TI  - Interpreting the Effectiveness of Opioids and Pregabalin for Pain Severity, Pain
      Interference, and Fatigue in Fibromyalgia Patients.
AB  - OBJECTIVE: To evaluate the effectiveness of opioids and/or pregabalin on patient
      reported outcomes among fibromyalgia (FM) patients based on levels of
      improvement. METHODS: A total of 1,421 FM patients were identified, with 3,082
      observational periods of opioids with or without pregabalin use between April
      2008 and February 2015. Patients were categorized by opioids, and pregabalin with
      and without opioids; opioids were designated by morphine equivalent dose (MED) of
      <= 20 (low MED), > 20 to < 100 (moderate MED), >= 100 (high MED), and pregabalin
      doses of <= 150 mg, 151 to 300 mg, and 301 to 450 mg. Proportions of patients
      meeting clinically relevant thresholds of >= 30% and >= 50% improvement for pain
      interference (ability to enjoy life; activity; mood; relationships; sleep), pain
      severity, and fatigue were compared among treatments, and area under the curve
      (AUC) for improvement and worsening of effects was determined, enabling ranking
      of treatments. Further analysis compared pregabalin doses. RESULTS: Pregabalin
      without opioids resulted in the highest proportions of patients with >= 30%
      improvement on all pain items and pain interference with "ability to enjoy life,"
      "activity" "mood," and "sleep." For the >= 50% threshold, pregabalin alone was
      highest for all pain interference items and for "average pain" and "worst pain."
      Pregabalin was consistently lowest across thresholds for fatigue, but showed
      better results combined with moderate MED opioids. Pregabalin doses recommended
      for treatment of FM (151 to 450 mg) generally resulted in the highest proportion
      of patients achieving thresholds relative to opioids. The AUC results were
      consistent with thresholds; pregabalin without opioids resulted in the greatest
      benefits with regard to improvement, with the highest ranking for overall
      improvement and overall effects. CONCLUSION: Pregabalin without opioids provided
      the most favorable outcomes overall based on >= 30% and >= 50% improvement
      thresholds and AUC, with support for moderate MED opioids + pregabalin in
      patients suffering from fatigue. While most patients took less than recommended
      pregabalin doses, higher doses may lead to improved outcomes.

PMID- 29064626
TI  - High-sensitivity C-reactive protein, low-density lipoprotein cholesterol and
      cardiovascular outcomes in patients with type 2 diabetes in the EXAMINE
      (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care)
      trial.
AB  - AIMS: We sought to assess the risk of major adverse cardiovascular events (MACE)
      by utilizing high-sensitivity C-reactive protein (hsCRP) level and low-density
      lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and recent acute
      coronary syndrome. MATERIALS AND METHODS: Study participants enrolled in the
      EXAMINE trial (Clinical trials registration number: NCT00968708) and were
      stratified by baseline hsCRP levels (<1, 1-3 and >3 mg/L). They were also sub
      divided into 4 groups according to baseline hsCRP (<=3 or >3 mg/L) and achieved
      LDL-C (<70 or >=70 mg/dL) levels. Among 5380 patients, the MACE rate, a composite
      of cardiovascular death, non-fatal acute myocardial infarction and non-fatal
      stroke, was evaluated during the 30 months of follow-up. RESULTS: Cumulative
      incidence of MACE was 11.5% (119 events), 14.6% (209 events) and 18.4% (287
      events) in patients with hsCRP levels of <1, 1 to 3 and >3 mg/L, respectively (P
      < .001). In patients with hsCRP >3 mg/L, the adjusted hazard ratio (95%
      confidence interval) was 1.42 (1.13, 1.78; P = .002) for MACE compared with
      patients with hsCRP <1 mg/L. MACE cumulative incidences were 11.0% (128 events),
      14.4% (100 events), 15.6% (194 events) and 21.3% (182 events) in patients with
      low LDL-C and low hsCRP, low LDL-C and high hsCRP, high LDL-C and low hsCRP, and
      high LDL-C and high hsCRP levels, respectively (P < .001). CONCLUSIONS: Levels of
      hsCRP were associated with recurrent cardiovascular events in patients with type
      2 diabetes and recent acute coronary syndrome, and this association appears to be
      independent of and additive to the achieved LDL-C level.

PMID- 29064628
TI  - Off-label prescriptions and decisions on reimbursement requests in Germany - a
      retrospective analysis.
AB  - BACKGROUND AND OBJECTIVES: "Off-label use" is defined as the prescription of
      pharmaceutical products outside their approved indications. Rare diseases
      frequently lack "on-label" treatment options. In order to avoid reimbursement
      claims following the prescription of off-label drugs, physicians in Germany can -
      on a case-by-case basis - file an application for cost coverage with the
      competent health insurance prior to treatment initiation. PATIENTS AND METHODS:
      We conducted a chart review for cost coverage requests submitted by two
      outpatient clinics at a university-affiliated dermatology department between 2010
      and 2012 (clinic for autoimmune diseases and urticaria clinic). Insurance
      providers, acceptance rates, reasons for rejection, and processing times were
      analyzed. RESULTS: The analysis showed that 56.8 % of applications for off-label
      use (n = 44) were approved during the first round. The rate increased to 75.0 %
      when including approvals granted after up to two rejections. The time between
      initial application and the response of health insurers was 49 days (median). In
      case of cost coverage approval, treatments were initiated 92 days (median) after
      the initial request. CONCLUSIONS: The present case series shows that, in the
      majority of cases, health insurers in Germany have agreed to reimburse the costs
      of proposed off-label therapies. A prospective study is required in order to
      evaluate whether current changes to legal regulations (GKV
      Versorgungsstrukturgesetz, Patientenrechtegesetz) adequately address the problems
      identified.

PMID- 29064629
TI  - Proteomics and Protein Adsorption on Hemodialysis Membranes.
AB  - Adsorption of plasma proteins onto the membrane surface during the hemodialysis
      session represents a key feature of membranes used for chronic dialysis therapy.
      In this issue of Proteomics-Clinical Applications, Han et al. originally describe
      how, by using proteomic technologies, the adsorptive properties of two membranes
      made from the same biomaterial (Polyamix) may have different flux characteristics
      (low flux and high flux, the former having smaller pore size). A total of 497
      differentially expressed proteins were identified in eluates obtained after in
      vivo hemodialysis: 320 proteins concentrated more in low-flux membrane
      (predominantly proteins with molecular weight 30-60 kDa) and 177 in high flux
      (most represented by proteins with molecular weight 10-15 kDa). Use of
      bioinformatics tools shed light on the involvement of adsorbed proteins in
      important biological pathways, such as the coagulation cascade and the complement
      system, again with some differences between the two membranes. The study
      indicates that flux characteristics of a biomaterial used for hemodialysis
      membrane strongly influence its adsorptive properties, and that proteomic
      application may provide information relevant to renal replacement therapy.

PMID- 29064630
TI  - Screening and separation of alpha-amylase inhibitors from Solanum nigrum with
      amylase-functionalized magnetic graphene oxide combined with high-speed counter
      current chromatography.
AB  - A screening method using alpha-amylase-functionalized magnetic graphene oxide
      combined with high-speed counter-current chromatography was proposed and utilized
      to screen and separate alpha-amylase inhibitors from extract of Solanum nigrum.
      The alpha-amylase-functionalized magnetic graphene oxide was characterized and
      found to demonstrate satisfactory structure, magnetic response (24.5 emu/g), and
      reusability (retained 90% of initial activity after five cycles). The conditions
      for the screening with alpha-amylase functionalized magnetic graphene oxide were
      optimized and set at pH 7.0 and 25 degrees C. As a result, two potent flavonoid
      compounds, apigenin-7-O-glucuronide (1) and astragalin (2), were separated and
      collected through high-speed counter-current chromatography and subjected to high
      performance liquid chromatography analysis with purity higher than 90% (according
      to HPLC data), which were identified as alpha-amylase inhibitors. These results
      suggested that utilization of alpha-amylase functionalized magnetic graphene
      oxide in the rapid screening and isolation bioactive compounds from complex
      natural products is a feasible and environmentally friendly method.

PMID- 29064631
TI  - Ferric Citrate Supplementation Reduces Red-Blood-Cell Aggregation and Improves
      CD163+ Macrophage-Mediated Hemoglobin Metabolism in a Rat Model of High-Fat-Diet
      Induced Obesity.
AB  - SCOPE: In adults, >90% of the daily iron requirement is derived from macrophage
      mediated heme iron, recycling from senescent red blood cells (RBCs) or free
      hemoglobin (Hb). Currently, the effects of pharmacological doses of iron
      supplementation on RBCs and heme iron recycling in obesity are unclear. METHODS
      AND RESULTS: Sprague Dawley rats are fed a standard diet or a 50% high-fat diet
      (HFD) with (0.25, 1, and 2 g of ferric iron per kg diet) or without ferric
      citrate supplementation for 12 weeks. Ferric iron increases hepatic iron
      accumulation in macrophages and hepatocyte-like cells. Compared with rats that
      received the standard diet, HFD-fed rats exhibit higher RBC aggregation and serum
      free Hb levels but lower LVV-hemorphin-7 levels. These effects are reversed by
      ferric citrate supplementation. Immunofluorescent staining reveals that ferric
      iron increases the expression of hepatic CD163+ macrophages and heme oxygenase
      (HO)-1. A further analysis reveals the dose-related effects of ferric iron on
      hepatic globin degradation proteins (cathepsin D and glyoxalase 1), cytochrome
      p450 reductase expression, and HO-1 enzyme activity. CONCLUSIONS: Ferric citrate
      supplementation reduces RBC aggregation and improves CD163+ macrophage-mediated
      Hb metabolism in HFD-induced obese rats. These findings suggest that ferric
      citrate may be explored as an alternative treatment method for RBC dysfunction.

PMID- 29064633
TI  - Proteomics analysis of Trichoplusia ni midgut epithelial cell brush border
      membrane vesicles.
AB  - The insect midgut epithelium is composed of columnar, goblet, and regenerative
      cells. Columnar epithelial cells are the most abundant and have membrane
      protrusions that form the brush border membrane (BBM) on their apical side. These
      increase surface area available for the transport of nutrients, but also provide
      opportunities for interaction with xenobiotics such as pathogens, toxins and host
      plant allelochemicals. Recent improvements in proteomic and bioinformatics tools
      provided an opportunity to determine the proteome of the T. ni BBM in
      unprecedented detail. This study reports the identification of proteins from BBM
      vesicles (BBMVs) using single dimension polyacrylamide gel electrophoresis
      coupled with multi-dimensional protein identification technology. More than 3000
      proteins were associated with the BBMV, of which 697 were predicted to possess
      either a signal peptide, at least one transmembrane domain or a GPI-anchor
      signal. Of these, bioinformatics analysis and manual curation predicted that 185
      may be associated with the BBMV or epithelial cell plasma membrane. These are
      discussed with respect to their predicted functions, namely digestion, nutrient
      uptake, cell signaling, development, cell-cell interactions, and other functions.
      We believe this to be the most detailed proteomic analysis of the lepidopteran
      midgut epithelium membrane to date, which will provide information to better
      understand the biochemical, physiological and pathological processes taking place
      in the larval midgut.

PMID- 29064632
TI  - The Effects of Platelet-Derived Growth Factor-BB on Human Dental Pulp Stem Cells
      Mediated Dentin-Pulp Complex Regeneration.
AB  - Dentin-pulp complex regeneration is a promising alternative treatment for the
      irreversible pulpitis caused by tooth trauma or dental caries. This process
      mainly relies on the recruitment of endogenous or the transplanted dental pulp
      stem cells (DPSCs) to guide dentin-pulp tissue formation. Platelet-derived growth
      factor (PDGF), a well-known potent mitogenic, angiogenic, and chemoattractive
      agent, has been widely used in tissue regeneration. However, the mechanisms
      underlying the therapeutic effects of PDGF on dentin-pulp complex regeneration
      are still unclear. In this study, we tested the effect of PDGF-BB on dentin-pulp
      tissue regeneration by establishing PDGF-BB gene-modified human dental pulp stem
      cells (hDPSCs) using a lentivirus. Our results showed that PDGF-BB can
      significantly enhance hDPSC proliferation and odontoblastic differentiation.
      Furthermore, PDGF-BB and vascular endothelial growth factor (VEGF) secreted by
      hDPSCs enhanced angiogenesis. The chemoattractive effect of PDGF-BB on hDPSCs was
      also confirmed using a Transwell chemotactic migration model. We further
      determined that PDGF-BB facilitates hDPSCs migration via the activation of the
      phosphatidylinositol 3 kinase (PI3K)/Akt signaling pathway. In vivo, CM-DiI
      labeled hDPSCs were injected subcutaneously into mice, and our results showed
      that more labeled cells were recruited to the sites implanted with calcium
      phosphate cement scaffolds containing PDGF-BB gene-modified hDPSCs. Finally, the
      tissue-engineered complexes were implanted subcutaneously in mice for 12 weeks,
      the Lenti-PDGF group generated more dentin-like mineralized tissue which showed
      positive staining for the DSPP protein, similar to tooth dentin tissue, and was
      surrounded by highly vascularized dental pulp-like connective tissue. Taken
      together, our data demonstrated that the PDGF-BB possesses a powerful function in
      prompting stem cell-based dentin-pulp tissue regeneration. Stem Cells
      Translational Medicine 2017;6:2126-2134.

PMID- 29064634
TI  - The ISTH Bleeding Assessment Tool and the risk of future bleeding.
AB  - : Essentials ISTH Bleeding Assessment Tool (ISTH-BAT) is used to assist the
      diagnosis of bleeding disorders. We examined whether the ISTH-BAT is capable of
      predicting the risk of future bleeding. 136 subjects were administered the ISTH
      BAT and followed for up to four years. The ISTH-BAT score failed to predict the
      risk of future bleeding. SUMMARY: Background The ISTH Bleeding Assessment Tool
      (ISTH-BAT) is a diagnostic tool used in subjects with suspected inherited
      bleeding disorders. Aim To evaluate whether the ISTH-BAT, applied at first work
      up in a tertiary-care center, predicts the risk of subsequent bleeding events.
      Methods This was an observational cohort study including all consecutive
      subjects, of either sex and any age, referred between 2011 and 2015 because of a
      suspected bleeding disorder. The analysis was restricted to those with an ISTH
      BAT score of >= 3. Incidence rates (IRs) of major bleeding (MB) and clinically
      relevant non-major bleeding (CRNMB) events were calculated as the number of
      events over accrued person-years. The main analysis was performed with Cox
      regression analysis, assessing an ISTH-BAT score of <= 5 versus a score of > 5,
      as well as the score as a continuous variable, and various covariates (sex, age,
      and presence/absence of a final diagnosis). Results One hundred and thirty-six
      subjects had a median ISTH-BAT score of 4 (range 3-18). Eleven subjects (8.1%)
      had a bleeding event during follow-up (one MB event; 10 CRNMB events). The
      overall IR of bleeding events per 100 person-years was 3.7 (95% confidence
      interval [CI] 1.8-6.6). No difference was observed between subjects with an ISTH
      BAT score of <= 5 and those with a score of > 5 (hazard ratio [HR] 1.2, 95% CI
      0.3-4.6). The results were similar when the ISTH-BAT score was considered as a
      continuous variable (HR 1.1, 95% CI 0.9-1.4). The IR of bleeding was increased in
      individuals with a diagnosis of a hemostatic defect (IR of 7.5 per 100 person
      years; HR 3.0, 95% CI 0.8-11.8). Conclusions The ISTH-BAT does not identify
      patients at increased risk of future bleeding events.

PMID- 29064635
TI  - Voltage-sensitive sodium channel mutations S989P + V1016G in Aedes aegypti confer
      variable resistance to pyrethroids, DDT and oxadiazines.
AB  - BACKGROUND: Aedes aegypti is a vector of several important human pathogens.
      Control efforts rely primarily on pyrethroid insecticides for adult mosquito
      control, especially during disease outbreaks. A. aegypti has developed resistance
      nearly everywhere it occurs and insecticides are used. An important mechanism of
      resistance is due to mutations in the voltage-sensitive sodium channel (Vssc)
      gene. Two mutations, in particular, S989P + V1016G, commonly occur together in
      parts of Asia. RESULTS: We have created a strain (KDR:ROCK) that contains the
      Vssc mutations S989P + V1016G as the only mechanism of pyrethroid resistance
      within the genetic background of Rockefeller (ROCK), a susceptible lab strain. We
      created KDR:ROCK by crossing the pyrethroid-resistant strain Singapore with ROCK
      followed by four backcrosses with ROCK and Vssc S989P + V1016G genotype
      selections. We determined the levels of resistance conferred to 17 structurally
      diverse pyrethroids, the organochloride DDT, and oxadiazines (VSSC blockers)
      indoxacarb (proinsecticide) and DCJW (the active metabolite of indoxacarb).
      Levels of resistance to the pyrethroids were variable, ranging from 21- to 107
      fold, but no clear pattern between resistance and chemical structure was
      observed. Resistance is inherited as an incompletely recessive trait. KDR:ROCK
      had a > 2000-fold resistance to DDT, 37.5-fold cross-resistance to indoxacarb and
      13.4-fold cross-resistance to DCJW. CONCLUSION: Etofenprox (and DDT) should be
      avoided in areas where Vssc mutations S989P + V1016G exist at high frequencies.
      We found that pyrethroid structure cannot be used to predict the level of
      resistance conferred by kdr. These results provide useful information for
      resistance management and for better understanding pyrethroid interactions with
      VSSC. (c) 2017 The Authors. Pest Management Science published by John Wiley &
      Sons Ltd on behalf of Society of Chemical Industry.

PMID- 29064636
TI  - Advanced online mass spectrometry detection of proteins separated by capillary
      isoelectric focusing after sequential injection.
AB  - Capillary isoelectric focusing hyphenated with mass spectrometry detection,
      following the sequential injection of the carrier ampholytes and the sample zone,
      is highly efficient for the characterization of proteins. The main advantage of
      the sequential injection protocol is that ampholytes, with pH ranges, which are
      not supposed to cover the isoelectric points of the sample components, can be
      used for separation. The method then allows online mass spectrometry detection of
      separated analytes either in the absence (substances that have left the pH
      gradient) or in the presence of low-level ampholytes (substances that are
      migrating within the pH gradient). The appearance of the substances within, or
      outside the pH gradient depends on, e.g., the composition of the ampholytes
      (broad or narrow pH range) or on the composition of electrolyte solutions. The
      experiments performed in coated capillaries (with polyvinyl alcohol or with
      polyacrylamide) show that the amount and the injection length of the ampholytes
      influence the length of the pH gradient formed in the capillary.

PMID- 29064637
TI  - Adsorption and Selective Recovery of Citric Acid with Poly(4-vinylpyridine).
AB  - Citric acid (CA) is an important organic acid that is produced on a large scale
      by fermentation. Current methods to recover CA from the fermentation broth
      require large amounts of chemicals and produce considerable amounts of waste,
      while not all CA can be recovered. The use of adsorbents can increase the degree
      of product recovery and reduce chemical consumption and waste generation. In this
      work, poly(4-vinylpyridine) (PVP) is evaluated as an adsorbent for CA recovery.
      It has a high adsorption capacity (>30 wt %) at low pH and a high selectivity for
      CA at moderate pH in the presence of sulfate anions, two conditions that are
      frequently encountered during CA recovery. PVP could be efficiently regenerated
      after adsorption using simple alcohols like methanol and ethanol. Considering
      selectivity and regeneration, PVP distinctly outperforms more common adsorbents
      for organic acids, including commercial strongly and weakly basic anion
      exchangers. The desirable adsorptive features of PVP for CA can be attributed to
      the low basicity of the pyridine group.

PMID- 29064638
TI  - How to model temporal changes in nontargeted metabolomics study? A Bayesian
      multilevel perspective.
AB  - Analysis of time series data addresses the question on mechanisms underlying
      normal physiology and its alteration under pathological conditions. However,
      adding time variable to high-dimension, collinear, noisy data is a challenge in
      terms of mining and analysis. Here, we used Bayesian multilevel modeling for time
      series metabolomics in vivo study to model different levels of random effects
      occurring as a consequence of hierarchical data structure. A multilevel linear
      model assuming different treatment effects with double exponential prior,
      considering major sources of variability and robustness to outliers was proposed
      and tested in terms of performance. The treatment effect for each metabolite was
      close to zero suggesting small if any effect of cancer on metabolomics profile
      change. The average difference in 964 signals for all metabolites varied by a
      factor ranging from 0.8 to 1.25. The inter-rat variability (expressed as a
      coefficient of variation) ranged from 3-30% across all metabolites with median
      around 10%, whereas the inter-occasion variability ranged from 0-30% with a
      median around 5%. Approximately 36% of metabolites contained outlying data
      points. The complex correlation structure between metabolite signals was
      revealed. We conclude that kinetics of metabolites can be modeled using tools
      accepted in pharmacokinetics type of studies.

PMID- 29064639
TI  - Guide to Dental Practice Act Compliance.

PMID- 29064640
TI  - Tech Trends: A look into the latest dental and general technology on the market.

PMID- 29064641
TI  - Dr. Bob. Snakes: The Stuff of Nightmaresssssss.

PMID- 29064642
TI  - Kids' Perceptions toward Children's Ward Healing Environments: A Case Study of
      Taiwan University Children's Hospital
AB  - This paper summarizes the opinions of experts who participated in designing the
      environment of a children's hospital and reports the results of a questionnaire
      survey conducted among hospital users. The grounded theory method was adopted to
      analyze 292 concepts, 79 open codes, 25 axial codes, and 4 selective codes; in
      addition, confirmatory factor analysis and reliability analysis were performed to
      identify elements for designing a healing environment in a children's hospital,
      and 21 elements from 4 dimensions, namely, emotions, space design, interpersonal
      interaction, and pleasant surroundings, were determined. Subsequently, this study
      examined the perceptions of 401 children at National Taiwan University Children's
      Hospital. The results revealed that, regarding the children's responses to the
      four dimensions and their overall perception, younger children accepted the
      healing environment to a significantly higher degree than did older children. The
      sex effect was significant for the space design dimension, and it was not
      significant for the other dimensions.

PMID- 29064648
TI  - Whipped Cream, Fast Cars and Dentistry.

PMID- 29064649
TI  - Modelling pH-Optimized Degradation of Microgel-Functionalized Polyesters
AB  - We establish a novel mathematical model to describe and analyze pH levels in the
      vicinity of poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate-co-N
      vinylimidazole) (VCL/AAEM/VIm) microgel-functionalized polymers during
      biodegradation. Biodegradable polymers, especially aliphatic polyesters
      (polylactide/polyglycolide/polycaprolactone homo- and copolymers), have a large
      range of medical applications including delivery systems, scaffolds, or stents
      for the treatment of cardiovascular diseases. Most of those applications are
      limited by the inherent drop of pH level during the degradation process. The
      combination of polymers with VCL/AAEM/VIm-microgels, which aims at stabilizing pH
      levels, is innovative and requires new mathematical models for the prediction of
      pH level evaluation. The mathematical model consists of a diffusion-reaction PDE
      system for the degradation including reaction rate equations and diffusion of
      acidic degradation products into the vicinity. A system of algebraic equations is
      coupled to the degradation model in order to describe the buffering action of the
      microgel. The model is validated against the experimental pH-monitored
      biodegradation of microgel-functionalized polymer foils and is available for the
      design of microgel-functionalized polymer components.

PMID- 29064650
TI  - The demographic features, clinical outcomes, prognosis and treatment options for
      patients with sarcomatoid carcinoma of the urinary bladder: a single centre
      experience.
AB  - INTRODUCTION: Carcinosarcoma of the bladder is a very rare neoplasm. The
      pathogenesis of carcinosarcomas is not clearly understood and remains a subject
      of debate. Whilst there is some research conceptualizing the histopathological
      findings of bladder carcinosarcomas, the demographic features, clinical outcomes,
      prognosis and treatment options remain unclear. MATERIALS AND METHODS: We
      analyzed 12 consecutive cases of patients with sarcoma-toid bladder cancer who
      were treated surgically at a single Urology Department be-tween 1999 and 2015.
      Radiology, pathology and surgical reports were reviewed to determine the
      pathological staging at the time of cystectomy. These were directly compared with
      230 patients having cystectomies for urothelial cell carcinoma. The sarcomatoid
      patients, were compared to patients with urothelial cell cancers. The other
      histological sub types, squamous cell (17), neuroendocrine (9), metastatic (7),
      mixed (4), adenocarcinoma (3), were not included. RESULTS AND CONCLUSION:
      Carcinosarcoma of the urinary bladder is often described in the literature as a
      highly malignant neoplasm that is rapidly lethal. We found that the sarcoma does
      not offer a worse prognosis than conventional high-grade urothelial car-cinoma.
      There is no significant difference in grade, stage, positive surgical margin
      rate, nodal involvement, associated prostate cancer or incidence rates of
      progression, all cause or disease specific mortality. There was a barely
      significant difference in carcinoma in-situ. However, carcinosarcomas are three
      times the volume of urothelial cell tumors which may contribute to its reputation
      as an aggressive tumour (44cc v 14cc). Sarcomatous elements do not appear, from
      our small study, to bestow a worse prognosis.

PMID- 29064651
TI  - Effectiveness and durability of solifenacin versus percutaneous tibial nerve
      stimulation versus their combination for the treatment of women with overactive
      bladder syndrome: a randomized controlled study with a follow-up of ten months.
AB  - PURPOSE: To assess effectiveness and durability of Solifenacin (SS) versus tibial
      nerve stimulation (PTNS) versus combination therapy (PTNS + SS) in women with
      overactive bladder syndrome (OAB). MATERIALS AND METHODS: 105 women with OAB were
      divided randomly into three groups of 35 patients each. In group A women received
      SS, in group B women underwent PTNS, in group C women underwent combination of
      PTNS + SS. Improvements in OAB symptoms were assessed with OABSS questionnaire;
      patients' quality of life was assessed with OAB-q SF questionnaire. Evaluation of
      effectiveness of treatments was performed with PGI-I questionnaire. OABSS and PGI
      I were also assessed monthly for ten months. RESULTS: All treatments were
      effective on symptoms. PTNS showed a greater effectiveness than SS, but PTNS + SS
      was more effective than SS and PTNS. Furthermore, PTNS + SS showed a greater
      duration of effectiveness than PTNS and SS. CONCLUSIONS: Combination of PTNS with
      SS showed more effectiveness and more durability than PTNS and SS alone.

PMID- 29064653
TI  - Prostate cancer recurrence in vas deferens - fusion image guide as an important
      tool in dignosis.
AB  - The biochemical recurrence after local treatment for prostate cancer is an often
      challenging condition of clinical management. The aim of this report is to
      demonstrate the importance of the association of various imaging methods in the
      identification and subsequent accurate percutaneous biopsy in patients with
      recurrence of prostate cancer, especially in unusual sites. An 86 years old male
      with biochemical recurrence, during radiological investigation a PET-MRI was
      noted the presence of an asymmetry of the vas deferens with PSMA- 68Ga uptaken,
      suggesting the recurrence. A percutaneous fusion biopsy with PET-MRI and
      ultrasound was performed using transrectal access using ultrasound confirming
      infiltrating adenocarcinoma of the wall of the vas deferens, compatible with
      neoplastic prostate recurrence. The fusion image technique combines the real-time
      view of the US to the possibility of higher definition and higher specificity,
      methods more anatomical detail as tomography and magnetic resonance imaging,
      simultaneously. High resolution acquired in PET / MR associated with image fusion
      allows orientation procedures, even in areas of difficult access, with greater
      accuracy than conventional techniques.

PMID- 29064652
TI  - Impact of testicular sperm extraction and testicular sperm aspiration on gonadal
      function in an experimental rat model.
AB  - PURPOSE: To assess the impact of sperm retrieval on the gonadal function of rats
      with impaired spermatogenesis by comparing testicular sperm extraction (TESE) to
      aspiration (TESA). The efficacy of these procedures to sperm obtainment was also
      compared. MATERIALS AND METHODS: A pilot study showed impaired spermatogenesis,
      but normal testosterone (T) production after a bilateral orchidopexy applied to
      26 rats, which were randomly assigned into four groups: TESE (n=7), TESA (n=7),
      SHAM (n=6) and Control (n=6). The T levels were measured through comparative
      analysis after the orchidopexy. RESULTS: There was no statistical difference in
      the animal's baseline T levels after orchidopexy in comparison to the controls:
      the TESE and TESA groups, 6.66+/-4.67ng/mL; the SHAM group (orchidopexy only),
      4.99+/-1.96ng/mL; and the Control, 4.75+/-1.45ng/ mL, p=0.27. Accordingly, no
      difference was found in the postoperative T levels: TESE, 5.35+/-4.65ng/mL; TESA,
      3.96+/-0.80ng/mL; SHAM, 3.70+/-1.27ng/mL; p=0.4. The number of sperm cells found
      through TESE (41.0+/-7.0) was significantly larger than that found through TESA
      (21.3+/-8.1, p=0.001). Moreover, higher tissue weight was found through TESE
      (0.09+/-0.02g versus 0.04+/-0.04g, p=0.04). CONCLUSIONS: The testicular sperm
      capture performed in rats through extraction or aspiration, after orchidopexy,
      did not significantly decrease the T levels. The amount of sperm found through
      testicular sperm extraction was higher than that through testicular sperm
      aspiration.

PMID- 29064654
TI  - An unusual presentation of urethral duplication presenting with chronic bladder
      retention, left scrotal transposition and left renal agenesis.
AB  - INTRODUCTION AND OBJECTIVE: Urethral duplication is a rare congenital anomaly,
      with roughly 200 cases reported in the literature (1). It is more frequent in
      males, with few cases reported in females. The clinical presentation differs
      according to the anatomical variant present. The duplication most commonly occurs
      in the sagittal plane with one urethra located ventrally and the other dorsally
      (2). Usually the ventral urethra is the more functional of both. Duplications
      occurring in the coronal plane are quite rare and they are usually associated
      with bladder duplication (3). The purpose of this paper was to present a video of
      a boy with an unusual urethral duplication form. MATERIALS AND METHODS: Patient
      was born premature due to oligohydramnios at 7 months-gestational age and he has
      initial diagnosis of hypospadia. Since then, he presented at least 7 febrile UTI
      and mother complained of difficult micturition and a presence of a mass at lower
      abdomen. Patient was referred to our institution and we identified urethral
      duplication with a glandar and scrotal meatus, palpable bladder and left penile
      hemiscrotum transposition. US and CT-scan showed left kidney agenesis and
      overdistended bladder. VCUG and retrograde urethrography showed duplication,
      presence of contrast in the seminal vesicles and complete catheterizing of both
      urethras was not possible. RESULTS: The topic urethra was dysplastic and not
      patent to a 4Fr plastic tube so we were unable to access it endoscopically. We
      performed initially a Mitrofanoff procedure to allow CIC and treat chronic
      retention. Six months later, we assessed both urethras surgically and concluded
      that dorsal urethra was dysplastic after 3cm still in the penile area and scrotal
      urethra was not possible to be catheterized. We excised the ventral urethra
      because of dribbling complaints up to bulbar area and reconstructed the scrotal
      transposition, keeping the topic urethra for cosmetic issues. Patient had
      excellent outcome, performs CIC every 4 hours and has not presented further UTI
      episodes. DISCUSSION AND CONCLUSION: The urethral duplication is an anomaly that
      has multiple anatomical presentations. There are several theories about the
      etiology, but none can explain all types of presentations. There is also more
      than one rating available, and the Effmann classification is the most detailed.
      The case exemplifies this varied spectrum of anatomic urethral duplication. It
      resembles the urethral duplication type IIa-Y, however, ventral urethra meatus
      was located in penoscrotal area and both urethras were at least partially
      hypoplastic/dysplastic associated with obstruction and bladder retention. In
      determining how to best manage a patient with Y-type urethral duplication, the
      caliber and quality of the orthotopic urethra must first be assessed. Published
      reports suggest that best outcomes are those using the ventral duplicated urethra
      for the reconstruction (4). In this case, none of urethras were functional and a
      supravesical outlet channel had to be provided. The treatment of this condition
      requires an individualized planning and a vast technical knowledge of
      reconstructive surgery.

PMID- 29064655
TI  - Saphenous-sparing laparoscopic inguinal lymphadenectomy.
AB  - INTRODUCTION: Inguinal lymphadenectomy is an integral part in the management of
      penile cancer. Video endoscopic in-guinal lymphadenectomy (VEIL) is emerging as a
      minimally invasive treatment to reduce postoperative complications. MATERIALS AND
      METHODS: 62 years old man underwent glansectomy for a squamous cell carcinoma
      (pT1b). At the physical examination one left inguinal lymph node was detectable
      (cN1). The chest-abdomen-pelvis CT was negative for me-tastasis. A 10-mm optical
      trocar and two 5mm operating trocar were placed. The optical trocar was placed in
      the apex of Scarpa's triangle after a skin incision and after the creation of a
      subcutaneous space by blunt finger dissection. The pCO2 was 8-10mmHg. The
      surgical technique involved the removal of superficial lymph nodes according to
      the scheme described by Deseler and of the deep lymph nodes. Sparing main venous
      structures and closing lymphatic vessels is im-portant to reduce post operative
      complications. At the end of the procedure, a suction drain was placed per side.
      RESULTS: Operative time was 90 minutes per side. Drains were removed on the
      seventh postoperative day. Hospital stay was 8 days and no postoperative
      complications occurred. The total number of nodes removed was 16 (8 per side)
      with 2 superficial positive nodes on the left side. CONCLUSION: ILND is burned by
      a high complication rate. VEIL provides a less invasive approach and a saphenous
      sparing technique ensures a lower complication rate, reducing lymphorrhea, skin
      necrosis and wound complications (1-3). In experienced laparoscopic hands, VEIL
      is a safe and effective treatment.

PMID- 29064656
TI  - Stage effect of chronic kidney disease in erectile function.
AB  - PURPOSE: The study aims to assess the influence of the stage of chronic kidney
      disease and glomerular filtration rate on prevalence and degree of erectile
      dysfunction. MATERIALS AND METHODS: This transversal study, conducted from May
      2013 to December 2015, included patients with chronic kidney disease in
      conservative treatment, stages III/IV/V. Erectile dysfunction was evaluated by
      the International Index of Erectile Function. Data classically associated with
      erectile dysfunction were obtained by medical record review. Erectile
      dysfunction, degree of erectile dysfunction, and other main variables associated
      with erectile dysfunction were compared between patients with chronic kidney
      disease on conservative treatment stages III versus IV/V using the Chi-square
      test. The relationship between score of the International Index of Erectile
      Dysfunction and glomerular filtration rate was established by Pearson correlation
      coefficient. RESULTS: Two hundred and forty five patients with chronic kidney
      disease in con-servative treatment participated of the study. The prevalence of
      erectile dysfunction in patients with chronic kidney disease in stages IV/V was
      greater than in stage III. Glomerular filtration rate positively correlated with
      score of the International Index of Erectile Dysfunction. CONCLUSIONS: The study
      suggests that chronic kidney disease progression (glomerular filtration rate
      decrease and advance in chronic kidney disease stages) worsen erectile function.
      Hypothetically, diagnosis and treatment of erectile dysfunction may be
      anticipated with the analysis of chronic kidney disease progression.

PMID- 29064658
TI  - Assessment of the Nurse Medication Administration Workflow Process
AB  - This paper presents findings of an observational study of the Registered Nurse
      (RN) Medication Administration Process (MAP) conducted on two comparable medical
      units in a large urban tertiary care medical center in Columbia, South Carolina.
      A total of 305 individual MAP observations were recorded over a 6-week period
      with an average of 5 MAP observations per RN participant for both clinical units.
      A key MAP variation was identified in terms of unbundled versus bundled MAP
      performance. In the unbundled workflow, an RN engages in the MAP by performing
      only MAP tasks during a care episode. In the bundled workflow, an RN completes
      medication administration along with other patient care responsibilities during
      the care episode. Using a discrete-event simulation model, this paper addresses
      the difference between unbundled and bundled workflow and their effects on
      simulated redesign interventions.

PMID- 29064659
TI  - Cobalt(II) Magnetic Metal-Organic Framework with an Effective Kagome Lattice,
      Large Surface Area, and High Spin-Canted Ordering Temperature.
AB  - To make a porous material with high magnetic ordering temperature is challenging
      because the low density of the material is adverse to the dense magnetic moment,
      a prerequisite to high-performance magnets. Herein, we report a hollow magnetic
      metal-organic framework (MMOF) [Co3(bpdc)3(tpt)0.66] 1 (H2bpdc = 4,4'
      biphenyldicarboxylic acid) with a Langmuir surface area of 1118 m2/g and spin
      canted long-range magnetic ordering up to 22 K. Such a high performance is owing
      to the unique antiferromagnetic Kagome lattice made of ferromagnetic Co3 clusters
      and conjugated 2,4,6-tri(4-pyridinyl)-1,3,5-triazine (tpt) ligands, which is
      closely coupled with each other via double-interpenetration of the porous
      networks. Moreover, a parameter defined as the product of magnetic
      ordering/blocking temperature and the surface area for measuring the performance
      of porous molecular magnets is proposed.

PMID- 29064657
TI  - The association between the outcomes of extraperitoneal laparoscopic radical
      prostatectomy and the anthropometric measurements of the prostate by magnetic
      resonance imaging.
AB  - INTRODUCTION AND OBJECTIVE: To determine the association between the
      anthropometric measurements by magnetic resonance imaging (MRI) and perioperative
      outcomes of extraperitoneal laparoscopic radical prostatectomy (ELRP). MATERIALS
      AND METHODS: From 2008 to June 2016, 86 patients underwent preoperative MRI prior
      to undergoing ELRP for localized prostate cancer. We analyzed the associations
      between anthropometric measurements of MRI and the perioperative outcomes of
      patients who underwent ELRP. RESULTS: The mean patient age was 69.61+/-8.30
      years. The medians of operating time and blood loss were 2.30 hours and 725.30ml,
      respectively. The total post-surgical complication rate was 1.16%. The median
      hospital stay was 6.50 days. The pathological stages for T2 and T3 were 45.74%
      and 34.04%, respectively. The rate as positive surgical margins (PSMs) was 18.09%
      (pT2 and pT3; 6.38% and 9.57%). The angles between pubic bone and prostate gland
      (angle 1&2), were significantly associated with operative time and hospital stay,
      respectively (p<0.05). There was no correlation between the pelvimetry and
      positive surgical margin. CONCLUSIONS: The findings of the present study suggest
      that anthropometric measurements of the MRI are related to operative difficulties
      in ELRP. This study confirmed that MRI planning is the key to preventing
      complications in ELRP.

PMID- 29064660
TI  - Graphene-Carbon-Metal Composite Film for a Flexible Heat Sink.
AB  - The heat generated from electronic devices such as light emitting diodes (LEDs),
      batteries, and highly integrated transistors is one of the major causes
      obstructing the improvement of their performance and reliability. Herein, we
      report a comprehensive method to dissipate the generated heat to a vast area by
      using the new type of graphene-carbon-metal composite film as a heat sink. The
      unique porous graphene-carbon-metal composite film that consists of an
      electrospun carbon nanofiber with arc-graphene (Arc-G) fillers and an
      electrochemically deposited copper (Cu) layer showed not only high electrical and
      thermal conductivity but also high mechanical stability. Accordingly, superior
      thermal management of LED devices to that of conventional Cu plates and excellent
      resistance stability during the repeated 10 000 bending cycles has been achieved.
      The heat dissipation of LEDs has been enhanced by the high heat conduction in the
      composite film, heat convection in the air flow, and thermal radiation at low
      temperature in the porous carbon structure. This result reveals that the graphene
      carbon-metal composite film is one of the most promising materials for a heat
      sink of electronic devices in modern electronics.

PMID- 29064661
TI  - Electrodeposition of Copper for Three-Dimensional Metamaterial Fabrication.
AB  - Metamaterials typically consist of metallic and dielectric repeating structures.
      Electrodeposition of copper is the preferred approach to fabricating the metallic
      part of the metamaterials of interest in this study. The highly variant
      topography requires chemical additives, like chloride ions, 3-mercapto-1
      propanesulfonic acid (MPSA), polyethylene glycol (PEG), and polyvinylpyrrolidone
      (PVP) to enhance bottom-up superfilling while maintaining terrace flatness. This
      study focuses on both experimental and computational investigations of the
      degradation potential of the additives and their adsorption mechanism in a highly
      acidic copper electrolyte in order to optimally parametrize the copper
      electrodeposition process. Results show Cl-MPSA-PEG-PVP additives perform well,
      but substitution of PVP with Janus Green B provides better terrace leveling.
      Additionally, NMR data show a quick and complete conversion of MPSA to bis(3
      sulfopropyl) disulfide (SPS) in the acidic copper bath. Finally, FEM simulations
      further show that the accelerator species may initially accumulate and be
      transported vertically until overplating, whereby they are transported laterally.

PMID- 29064662
TI  - Near-Infrared Light Triggered Upconversion Optogenetic Nanosystem for Cancer
      Therapy.
AB  - In vivo the application of optogenetic manipulation in deep tissue is seriously
      obstructed by the limited penetration depth of visible light that is continually
      applied to activate a photoactuator. Herein, we designed a versatile upconversion
      optogenetic nanosystem based on a blue-light-mediated heterodimerization module
      and rare-earth upconversion nanoparticles (UCNs). The UCNs worked as a
      nanotransducer to convert external deep-tissue-penetrating near-infrared (NIR)
      light to local blue light to noninvasively activate photoreceptors for
      optogenetic manipulation in vivo. In this, we demonstrated that deeply
      penetrating NIR light could be used to control the apoptotic signaling pathway of
      cancer cells in both mammalian cells and mice by UCNs. We believe that this
      interesting NIR-light-responsive upconversion optogenetic nanotechnology has
      significant application potentials for both basic research and clinical
      applications in vivo.

PMID- 29064663
TI  - AFM Nanoindentation To Quantify Mechanical Properties of Nano- and Micron-Sized
      Crystals of a Metal-Organic Framework Material.
AB  - The mechanical properties of individual nanocrystals and small micron-sized
      single crystals of metal-organic frameworks (MOFs), hitherto, cannot be measured
      directly by employing the conventional instrumented nanoindentation approach.
      Here we propose the application of atomic force microscopy (AFM)-based
      nanoindentation technique, equipped with a calibrated diamond cube-corner
      indenter tip to quantify the Young's modulus, hardness, adhesion energy, and
      interfacial and fracture strengths of a zeolitic imidazolate framework (ZIF-8)
      porous material. We use ZIF-8 as a model MOF system to develop AFM
      nanoindentation leveraging the concept of unloading strain rate, enabling us to
      critically assess the practicality and technical limitations of AFM to achieve
      quantitative measurements of fine-scale MOF crystals. We demonstrate the
      advantages of using a high unloading strain rate (epsilon > 60 s-1) to yield
      reliable force-displacement data in the few MUN load range, corresponding to a
      shallow indentation depth of ~10s nm. We found that the Young's moduli (~3-4 GPa)
      determined by AFM nanoindentation of the nanocrystals (<500 nm) and micron-sized
      crystals (~2 MUm) are in agreement with magnitudes derived previously from other
      techniques, namely instrumented nanoindentation and Brillouin spectroscopy
      (however, these methods requiring large 100-MUm sized crystals) and also in line
      with density functional theory predictions of an idealized ZIF-8 crystal.

PMID- 29064664
TI  - Nitrogenase Cofactor Assembly: An Elemental Inventory.
AB  - Nitrogenase is known for its remarkable ability to catalyze the reduction of N2
      to NH3, and C1 substrates to short-chain hydrocarbon products, under ambient
      conditions. The best-studied Mo-nitrogenase utilizes a complex metallocofactor as
      the site of substrate binding and reduction. Designated the M-cluster, this
      [MoFe7S9C(R-homocitrate)] cluster can be viewed as [MoFe3S3] and [Fe4S3]
      subclusters bridged by three MU2-sulfides and one MU6-interstitial carbide, with
      its Mo end further coordinated by an R-homocitrate moiety. The unique cofactor
      has attracted considerable attention ever since its discovery; however, the
      complexity of its structure has hindered mechanistic understanding and chemical
      synthesis of this cofactor. Motivated by the pressing questions related to the
      structure and function of the nitrogenase cofactor, one major thrust of our
      research has been to unravel the key biosynthetic steps of this metallocluster to
      cultivate a deeper understanding of these reactions and their effects on
      functionalizing the cofactor. In this Account, we will discuss our recent work
      that provides insights into how simple Fe and S atoms, along with a single C
      atom, a heterometallic Mo atom and an organic homocitrate entity, are assembled
      into one of the most complex metalloclusters known in Nature. Combined
      biochemical, spectroscopic and structural studies have led us to a working model
      of M-cluster assembly, which starts with the sequential synthesis of small
      [Fe2S2] and [Fe4S4] units by NifS/U, followed by the coupling and rearrangement
      of two [Fe4S4] clusters on NifB concomitant with the insertion of an interstitial
      carbide and a "9th sulfur" that give rise to a [Fe8S9C] core that is nearly
      indistinguishable in structure to the M-cluster except for the absence of Mo and
      homocitrate. This 8Fe core is then matured into an M-cluster on NifEN upon
      substitution of a Mo-homocitrate conjugate for one terminal Fe atom of the
      cluster prior to transfer of the M-cluster to its target binding site in the
      catalytic component of Mo-nitrogenase. Taking stock of the elemental inventory
      during the cofactor assembly process, the core Fe and S atoms are derived from
      modular fusion of FeS building blocks, going through 2Fe, 4Fe and 8Fe stages to
      generate an 8Fe core of the cofactor. However, such a flow of Fe/S along the
      biosynthetic pathway of the M-cluster is "intervened" by the insertion of C and
      Mo, which renders the cofactor unique in structure and reactivity. Insertion of C
      occurs through a novel, radical SAM-dependent mechanism, which involves SN2-type
      methyl transfer from SAM to a [Fe4S4] cluster pair, hydrogen abstraction of the
      transferred methyl group by a SAM-derived 5'-dA. radical, and further
      deprotonation of the resultant methylene radical concomitant with radical
      chemistry-based coupling and rearrangement of the [Fe4S4] cluster pair into an
      [Fe8S9C] core. Insertion of Mo, on the other hand, employs an ATPase-dependent
      mechanism that parallels metal trafficking in the biosynthesis of molybdopterin
      and CO dehydrogenase cofactors. These findings provide a nice framework for
      further exploration of the "black box" of nitrogenase cofactor assembly and
      function.

PMID- 29064665
TI  - An Iron-Porphyrin Complex with Large Easy-Axis Magnetic Anisotropy on Metal
      Substrate.
AB  - Easy-axis magnetic anisotropy separates two magnetic states with opposite
      magnetic moments, and single magnetic atoms and molecules with large easy-axis
      magnetic anisotropy are highly desired for future applications in high-density
      data storage and quantum computation. By tuning the metalation reaction between
      tetra-pyridyl-porphyrin molecules and Fe atoms, we have stabilized the so-called
      initial complex, an intermediate state of the reaction, on Au(111) substrate, and
      investigated the magnetic property of this complex at a single-molecule level by
      low-temperature scanning tunneling microscopy and spectroscopy. As revealed by
      inelastic electron tunneling spectroscopy in magnetic field, this Fe-porphyrin
      complex has magnetic anisotropy energy of more than 15 meV with its easy-axis
      perpendicular to the molecular plane. Two magnetic states with opposite spin
      directions are discriminated by the dependence of spin-flip excitation energy on
      magnetic field and are found to have long spin lifetimes. Our density functional
      theory calculations reveal that the Fe atom in this complex, decoupled from Au
      substrate by a weak ligand field with elongated Fe-N bonds, has a high-spin state
      S = 2 and a large orbital angular momentum L = 2, which give rise to easy-axis
      anisotropy perpendicular to the molecular plane and large magnetic anisotropy
      energy by spin-orbit coupling. Since the Fe atom is protected by the molecular
      ligand, the complex can be processed at room or even higher temperatures. The
      reported system may have potential applications in nonvolatile data storage, and
      our work demonstrates on-surface metalation reactions can be utilized to
      synthesize organometallic complexes with large magnetic anisotropy.

PMID- 29064666
TI  - Few-Layer Thin-Film Metallic Glass-Enhanced Optical Properties of ZnO
      Nanostructures.
AB  - A few layers of Cu-based (Cu47Zr42Al7Ti4) thin-film metallic glasses (TFMGs) were
      sputtered on hydrothermally synthesized ZnO nanowires/glass and ZnO
      nanotubes/glass to fabricate UV photodetectors. The few layers of Cu-based TFMG
      are ultrathin at ~0.98 nm and have a noncrystalline metal structure according to
      X-ray diffraction, Raman, photoluminescence, and high-temperature transmission
      electron microscopy verification. The photoresponse performance of the coated few
      layers Cu-TFMG samples was enhanced 1680-7700% compared with the noncoated
      sample. The few-layers Cu-TFMG has high transmittance ~90% in the visible band
      and creates a large capacitor to absorb UV photocurrent and release dark current.

PMID- 29064667
TI  - Manganese-Oxygen Intermediates in O-O Bond Activation and Hydrogen-Atom Transfer
      Reactions.
AB  - Biological systems capitalize on the redox versatility of manganese to perform
      reactions involving dioxygen and its derivatives superoxide, hydrogen peroxide,
      and water. The reactions of manganese enzymes influence both human health and the
      global energy cycle. Important examples include the detoxification of reactive
      oxygen species by manganese superoxide dismutase, biosynthesis by manganese
      ribonucleotide reductase and manganese lipoxygenase, and water splitting by the
      oxygen-evolving complex of photosystem II. Although these enzymes perform very
      different reactions and employ structurally distinct active sites, manganese
      intermediates with peroxo, hydroxo, and oxo ligation are commonly proposed in
      catalytic mechanisms. These intermediates are also postulated in mechanisms of
      synthetic manganese oxidation catalysts, which are of interest due to the earth
      abundance of manganese. In this Account, we describe our recent efforts toward
      understanding O-O bond activation pathways of MnIII-peroxo adducts and hydrogen
      atom transfer reactivity of MnIV-oxo and MnIII-hydroxo complexes. In biological
      and synthetic catalysts, peroxomanganese intermediates are commonly proposed to
      decay by either Mn-O or O-O cleavage pathways, although it is often unclear how
      the local coordination environment influences the decay mechanism. To address
      this matter, we generated a variety of MnIII-peroxo adducts with varied ligand
      environments. Using parallel-mode EPR and Mn K-edge X-ray absorption techniques,
      the decay pathway of one MnIII-peroxo complex bearing a bulky macrocylic ligand
      was investigated. Unlike many MnIII-peroxo model complexes that decay to oxo
      bridged-MnIIIMnIV dimers, decay of this MnIII-peroxo adduct yielded mononuclear
      MnIII-hydroxo and MnIV-oxo products, potentially resulting from O-O bond
      activation of the MnIII-peroxo unit. These results highlight the role of ligand
      sterics in promoting the formation of mononuclear products and mark an important
      step in designing MnIII-peroxo complexes that convert cleanly to high-valent Mn
      oxo species. Although some synthetic MnIV-oxo complexes show great potential for
      oxidizing substrates with strong C-H bonds, most MnIV-oxo species are sluggish
      oxidants. Both two-state reactivity and thermodynamic arguments have been put
      forth to explain these observations. To address these issues, we generated a
      series of MnIV-oxo complexes supported by neutral, pentadentate ligands with
      systematically perturbed equatorial donation. Kinetic investigations of these
      complexes revealed a correlation between equatorial ligand-field strength and
      hydrogen-atom and oxygen-atom transfer reactivity. While this trend can be
      understood on the basis of the two-state reactivity model, the reactivity trend
      also correlates with variations in MnIII/IV reduction potential caused by changes
      in the ligand field. This work demonstrates the dramatic influence simple ligand
      perturbations can have on reactivity but also illustrates the difficulties in
      understanding the precise basis for a change in reactivity. In the enzyme
      manganese lipoxygenase, an active-site MnIII-hydroxo adduct initiates substrate
      oxidation by abstracting a hydrogen atom from a C-H bond. Precedent for this
      chemistry from synthetic MnIII-hydroxo centers is rare. To better understand
      hydrogen-atom transfer by MnIII centers, we developed a pair of MnIII-hydroxo
      complexes, formed in high yield from dioxygen oxidation of MnII precursors,
      capable of attacking weak O-H and C-H bonds. Kinetic and computational studies
      show a delicate interplay between thermodynamic and steric influences in hydrogen
      atom transfer reactivity, underscoring the potential of MnIII-hydroxo units as
      mild oxidants.

PMID- 29064668
TI  - Real-Time Observation of Exciton-Phonon Coupling Dynamics in Self-Assembled
      Hybrid Perovskite Quantum Wells.
AB  - Self-assembled hybrid perovskite quantum wells have attracted attention due to
      their tunable emission properties, ease of fabrication, and device integration.
      However, the dynamics of excitons in these materials, especially how they couple
      to phonons, remains an open question. Here, we investigate two widely used
      materials, namely, butylammonium lead iodide (CH3(CH2)3NH3)2PbI4 and
      hexylammonium lead iodide (CH3(CH2)5NH3)2PbI4, both of which exhibit broad
      photoluminescence tails at room temperature. We performed femtosecond vibrational
      spectroscopy to obtain a real-time picture of the exciton-phonon interaction and
      directly identified the vibrational modes that couple to excitons. We show that
      the choice of the organic cation controls which vibrational modes the exciton
      couples to. In butylammonium lead iodide, excitons dominantly couple to a 100 cm
      1 phonon mode, whereas in hexylammonium lead iodide, excitons interact with
      phonons with frequencies of 88 and 137 cm-1. Using the determined optical phonon
      energies, we analyzed photoluminescence broadening mechanisms. At low
      temperatures (<100 K), the broadening is due to acoustic phonon scattering,
      whereas at high temperatures, LO phonon-exciton coupling is the dominant
      mechanism. Our results help explain the broad photoluminescence line shape
      observed in hybrid perovskite quantum wells and provide insights into the
      mechanism of exciton-phonon coupling in these materials.

PMID- 29064669
TI  - Highly Specific Binding on Antifouling Zwitterionic Polymer-Coated Microbeads as
      Measured by Flow Cytometry.
AB  - Micron- and nano-sized particles are extensively used in various biomedical
      applications. However, their performance is often drastically hampered by the
      nonspecific adsorption of biomolecules, a process called biofouling, which can
      cause false-positive and false-negative outcomes in diagnostic tests. Although
      antifouling coatings have been extensively studied on flat surfaces, their use on
      micro- and nanoparticles remains largely unexplored, despite the widespread
      experimental (specifically, clinical) uncertainties that arise because of
      biofouling. Here, we describe the preparation of magnetic micron-sized beads
      coated with zwitterionic sulfobetaine polymer brushes that display strong
      antifouling characteristics. These coated beads can then be equipped with
      recognition elements of choice, to enable the specific binding of target
      molecules. First, we present a proof of principle with biotin-functionalized
      beads that are able to specifically bind fluorescently labeled streptavidin from
      a complex mixture of serum proteins. Moreover, we show the versatility of the
      method by demonstrating that it is also possible to functionalize the beads with
      mannose moieties to specifically bind the carbohydrate-binding protein
      concanavalin A. Flow cytometry was used to show that thus-modified beads only
      bind specifically targeted proteins, with minimal/near-zero nonspecific protein
      adsorption from other proteins that are present. These antifouling zwitterionic
      polymer-coated beads, therefore, provide a significant advancement for the many
      bead-based diagnostic and other biosensing applications that require stringent
      antifouling conditions.

PMID- 29064670
TI  - Pair of Stereodynamic Chiral Benzylicaldehyde Probes for Determination of
      Absolute Configuration of Amino Acid Residues in Peptides by Mass Spectrometry.
AB  - This paper describes a simple method to determine the absolute configuration of
      amino acids residues in peptides by mass spectrometry using a newly developed
      pair of mass-tagged chiral probes without the requirement of reference standards.
      A pair of benzylicaldehyde probes, 1-(S)-1H in S configuration and 2-(R)-2D in
      deuterium-labeled R configuration with the ratio of 1:1, were synthesized for in
      situ condensation with amino acid residues and transformed into a pair of
      stereodynamic imine products. The characteristic intensity difference observed in
      mass spectrometry can be used to determine the absolute configuration and to
      quantify the enantiomeric composition of chiral amino acid residues. Significant
      chiral recognition ability was achieved for 18 natural chiral amino acids and for
      one beta-amino acid by comparing the ion intensity ratio of imine products I[1
      (S)-1H-AA]- to I[2-(R)-2D-AA]-. For 16 kinds of amino acids, the L form of the
      amino acids was more reactive with 1-(S)-1H, while D configuration amino acids
      preferred to react with 2-(R)-2D. However, for three kinds of amino acid, the
      opposite result was obtained. The configurations of the residues in the peptides,
      Phe-Tyr-Ala, D-Phe-Tyr-Ala, Val-Pro-Phe-D-Leu-Met, Val-Pro-Phe-Leu-D-Met, as well
      as in a natural peptide with unknown chirality were determined by acid hydrolysis
      followed by the present method. In addition, molecular modeling results
      illustrate that the recognition process is mainly controlled by kinetic factors.
      Using the new probes coupled with a mass spectrometry approach avoids time
      consuming workup and separation steps. We expect that the probes could be applied
      as tools to determine the absolute configuration of amino acid residues in
      proteins in future research.

PMID- 29064671
TI  - Correction to Troponin C Mutations Partially Stabilize the Active State of
      Regulated Actin and Fully Stabilize the Active State When Paired with Delta14
      TnT.

PMID- 29064672
TI  - Fluorogenic Protein Labeling Probes to Study the Morphological Interplay between
      PreLamin and Mature Lamin.
AB  - Although many protein labeling probes have been developed to elucidate the
      trafficking and turnover processes of cell surface proteins, real-time tracking
      of intracellular proteins remains a challenging task. Herein, we describe a new
      design to construct a cell-permeable, photostable, and far-red fluorescent turn
      on probe to enable no-wash, organelle-specific, and long-term visualization of
      intracellular SNAP-tagged proteins in living cells. When the probe was used in
      dual-color pulse chase labeling experiments to differentiate between preLamin and
      mature Lamin, our results reveal that the shape of mature Lamin can be altered by
      the newly synthesized preLamin and that this alteration is progressive,
      cumulative, and due to a concentration-dependent dominant-negative effect of
      preLamin. We believe that this probe can also be applied to other intracellular
      proteins whose cellular localization and synthesis changes dynamically in
      response to external stimuli.

PMID- 29064673
TI  - Intramembrane Thiol Oxidoreductases: Evolutionary Convergence and Structural
      Controversy.
AB  - During oxidative protein folding, disulfide bond formation is catalyzed by thiol
      oxidoreductases. Through dedicated relay pathways, the disulfide is generated in
      donor enzymes, passed to carrier enzymes, and subsequently delivered to target
      proteins. The eukaryotic disulfide donors are flavoenzymes, Ero1 in the
      endoplasmic reticulum and Erv1 in mitochondria. In prokaryotes, disulfide
      generation is coupled to quinone reduction, catalyzed by intramembrane donor
      enzymes, DsbB and VKOR. To catalyze de novo disulfide formation, these different
      disulfide donors show striking structural convergence at several levels. They
      share a four-helix bundle core structure at their active site, which contains a
      CXXC motif at a helical end. They have also evolved a flexible loop with shuttle
      cysteines to transfer electrons to the active site and relay the disulfide bond
      to the carrier enzymes. Studies of the prokaryotic VKOR, however, have stirred
      debate about whether the human homologue adopts the same topology with four
      transmembrane helices and uses the same electron-transfer mechanism. The
      controversies have recently been resolved by investigating the human VKOR
      structure and catalytic process in living cells with a mass spectrometry-based
      approach. Structural convergence between human VKOR and the disulfide donors is
      found to underlie cofactor reduction, disulfide generation, and electron
      transfer.

PMID- 29064675
TI  - Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal
      Phosphoproteome.
AB  - Alcohol consumption during adolescence is deleterious to the developing brain and
      leads to persistent deficits in adulthood. Several results provide strong
      evidence for ethanol-associated alterations in glutamatergic signaling and
      impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a
      well-known and well-documented mechanism in memory processes, but information on
      phosphoprotein alterations in hippocampus after ethanol exposure is limited. This
      study focuses on age-related changes in the hippocampal phosphoproteome after
      acute alcohol administration. We have compared the phosphoprotein expression in
      the hippocampus of adult and adolescent Wistar rats treated with a single dose of
      ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein
      enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic
      analysis revealed that 13 proteins were differentially affected by age, ethanol
      administration, or both. Most of these proteins are involved in neuroprotection
      and are expressed less in young rats treated with ethanol. We conclude that acute
      alcohol induces important changes in the expression of phosphoproteins in the
      hippocampus that could increase the risk of neurodegenerative disorders,
      especially when the alcohol exposure begins in adolescence.

PMID- 29064676
TI  - Identification and Biosynthesis of 1-Mercaptoethanesulfonic Acid (1-MES), an
      Analogue of Coenzyme M, Found Widely in the Methanogenic Archaea.
AB  - Here I report on the identification of 1-mercaptoethanesulfonic acid (1-MES), an
      analogue of 2-mercaptoethanesulfonic acid (coenzyme M, HSCoM). 1-MES and HSCoM
      were both present in the growth media of eight different methanogens at
      concentrations ranging from ~1 to 100 MUM. In an effort to determine a chemical
      origin of 1-MES, several plausible chemical routes were examined each assuming
      that HSCoM was the precursor. In all examined routes, no 1-MES was formed.
      However, 1-MES was formed when a solution of vinylsulfonic acid and sulfide were
      exposed to ultraviolet light. On the basis of these results, I conclude 1-MES is
      formed enzymatically. This was confirmed by growing a culture of Methanococcus
      maripaludis S2 in the presence of [1,1',2,2'-2H4]HSCoM and measuring the
      incorporation of deuterium into 1-MES. 1-MES incorporated three of the four
      deuteriums from the fed HSCoM. This result is consistent with the abstraction of
      a C-2 deuterium of the HSCoM, likely by a 5'-dAdoCH2* radical, followed by a
      radical rearrangement in which the sulfonic acid moves to position C-1, followed
      by abstraction of a H* likely from 5'-dAdoCH2D. At present, the reason for the
      production of 1-MES is not clear. This is the first report of the occurrence of 1
      MES in Nature.

PMID- 29064674
TI  - Heterogeneity between Two alpha Subunits of alpha2beta2 Human Hemoglobin and O2
      Binding Properties: Raman, 1H Nuclear Magnetic Resonance, and Terahertz Spectra.
AB  - Following a previous detailed investigation of the beta subunit of alpha2beta2
      human adult hemoglobin (Hb A), this study focuses on the alpha subunit by using
      three natural valency hybrid alpha(Fe2+-deoxy/O2)beta(Fe3+) hemoglobin M (Hb M)
      in which O2 cannot bind to the beta subunit: Hb M Hyde Park (beta92His -> Tyr),
      Hb M Saskatoon (beta63His -> Tyr), and Hb M Milwaukee (beta67Val -> Glu). In
      contrast with the beta subunit that exhibited a clear correlation between O2
      affinity and Fe2+-His stretching frequencies, the Fe2+-His stretching mode of the
      alpha subunit gave two Raman bands only in the T quaternary structure. This means
      the presence of two tertiary structures in alpha subunits of the alpha2beta2
      tetramer with T structure, and the two structures seemed to be nondynamical as
      judged from terahertz absorption spectra in the 5-30 cm-1 region of Hb M
      Milwaukee, alpha(Fe2+-deoxy)beta(Fe3+). This kind of heterogeneity of alpha
      subunits was noticed in the reported spectra of a metal hybrid Hb A like
      alpha(Fe2+-deoxy)beta(Co2+) and, therefore, seems to be universal among alpha
      subunits of Hb A. Unexpectedly, the two Fe-His frequencies were hardly changed
      with a large alteration of O2 affinity by pH change, suggesting no correlation of
      frequency with O2 affinity for the alpha subunit. Instead, a new Fe2+-His band
      corresponding to the R quaternary structure appeared at a higher frequency and
      was intensified as the O2 affinity increased. The high-frequency counterpart was
      also observed for a partially O2-bound form, alpha(Fe2+-deoxy)alpha(Fe2+
      O2)beta(Fe3+)beta(Fe3+), of the present Hb M, consistent with our previous
      finding that binding of O2 to one alpha subunit of T structure alpha2beta2
      tetramer changes the other alpha subunit to the R structure.

PMID- 29064677
TI  - Characterization and Elimination of Undesirable Protein Residues in Plant Cell
      Wall Materials for Enhancing Lignin Analysis by Solution-State Nuclear Magnetic
      Resonance Spectroscopy.
AB  - Protein polymers exist in every plant cell wall preparation, and they interfere
      with lignin characterization and quantification. Here, we report the structural
      characterization of the residual protein peaks in 2D NMR spectra in corn cob and
      kenaf samples and note that aromatic amino acids are ubiquitous and evident in
      spectra from various other plants and tissues. The aromatic correlations from
      amino acid residues were identified and assigned as phenylalanine and tyrosine.
      Phenylalanine's 3/5 correlation peak is superimposed on the peak from typical
      lignin p-hydroxyphenyl (H-unit) structures, causing an overestimation of the H
      units. Protein contamination also occurs when using cellulases to prepare enzyme
      lignins from virtually protein-free wood samples. We used a protease to remove
      the protein residues from the ball-milled cell walls, and we were able to reveal
      H-unit structures in lignins more clearly in the 2D NMR spectra, providing a
      better basis for their estimation.

PMID- 29064678
TI  - Multi-Stimuli-Responsive Metallogel Molded from a Pd2L4-Type Coordination Cage:
      Selective Removal of Anionic Dyes.
AB  - A self-assembled binuclear coordination cage of the Pd2L4 formulation has been
      constructed by complexation of Pd(NO3)2 with N, N'-bis(3
      pyridylmethyl)naphthalenediimide (L). The cage, i.e., [Pd2(L)4](NO3)4 (1),
      displayed a further self-assembly phenomenon to afford a gel phase, upon
      dissolution in either dimethyl sulfoxide or acetonitrile-water (1:1) followed by
      standing at room temperature. It was observed that a synergy among the metal ion,
      ligand, counteranion, solvent, and concentration played a vital role for
      metallogel formation. The morphology of the metallogel as observed from
      microscopy studies revealed the formation of a rare variety of nanoscale metal
      organic particles. Salient features of the gel include the thixotropic
      (mechanoresponsive) nature, in addition to the reversible chemical-stimuli
      responsive behavior. The presence of naphthalenediimide moieties at the backbone
      of the cage and the cationic nature of the cavity of the cage could be exploited
      to study the functional aspects of the gel. The porous gel exhibited the
      abilities to uptake pyrene as a guest and to selectively remove anionic dyes from
      aqueous solutions. The gel could bind representative anionic dyes like "acid blue
      93" and "methyl orange" in the absence or presence of certain cationic dyes,
      making the material suitable for selective dye removal applications.

PMID- 29064681
TI  - Excited State Properties of Heteroleptic Cu(I) 4H-Imidazolate Complexes.
AB  - The excited state properties of three heteroleptic copper(I) xantphos 4H
      imidazolate complexes are investigated by means of femtosecond and nanosecond
      time-resolved transient absorption spectroscopy in dichloromethane solution. The
      subpicosecond spectral changes observed after excitation into the MLCT absorption
      band are interpreted as intersystem crossing from the singlet to the triplet
      manifold. This interpretation is corroborated by DFT and TD-DFT results,
      indicating a comparable molecular geometry in the ground state (and hence the
      nonrelaxed singlet state) and the excited triplet state. Population of the
      triplet state is followed by planarization of the N-aryl rings of the 4H
      imidazolate ligand on a 10 ps time scale. The planarization strongly depends on
      the substitution pattern of the N-aryls and correlates with the reduced moment of
      inertia for the planarization motion. The triplet state subsequently decays to
      the ground state in about 100 ns. These results demonstrate that the excited
      state processes of copper(I) complexes depend on the specific ligand(s) and their
      substitution pattern. Thus, the work presented points to a possibility to design
      copper(I) complexes with specific photophysical properties.

PMID- 29064680
TI  - Plant Translation Initiation Complex eIFiso4F Directs Pokeweed Antiviral Protein
      to Selectively Depurinate Uncapped Tobacco Etch Virus RNA.
AB  - Pokeweed antiviral protein (PAP) is a ribosome inactivating protein (RIP) that
      depurinates the sarcin/ricin loop (SRL) of rRNA, inhibiting protein synthesis.
      PAP depurinates viral RNA, and in doing so, lowers the infectivity of many plant
      viruses. The mechanism by which PAP accesses uncapped viral RNA is not known,
      impeding scientists from developing effective antiviral agents for the prevention
      of the diseases caused by uncapped RNA viruses. Kinetic rates of PAP interacting
      with tobacco etch virus (TEV) RNA, in the presence and absence of eIFiso4F, were
      examined, addressing how the eIF affects selective PAP targeting and depurination
      of the uncapped viral RNA. PAP-eIFs copurification assay and fluorescence
      resonance energy transfer demonstrate that PAP forms a ternary complex with the
      eIFiso4G and eIFiso4E, directing the depurination of uncapped viral RNA. eIFiso4F
      selectively targets PAP to depurinate TEV RNA by increasing PAP's specificity
      constant for uncapped viral RNA 12-fold, when compared to the depurination of an
      oligonucleotide RNA that mimics the SRL of large rRNA, and cellular capped
      luciferase mRNA. This explains how PAP is able to lower infectivity of pokeweed
      viruses, while preserving its own ribosomes and cellular RNA from depurination:
      PAP utilizes cellular eIFiso4F in a novel strategy to target uncapped viral RNA.
      It may be possible to modulate and utilize these PAP-eIFs interactions for their
      public health benefit; by repurposing them to selectively target PAP to
      depurinate uncapped viral RNA, many plant and animal diseases caused by these
      viruses could be alleviated.

PMID- 29064679
TI  - Mutation of Asn-475 in the Venezuelan Equine Encephalitis Virus nsP2 Cysteine
      Protease Leads to a Self-Inhibited State.
AB  - The alphaviral nsP2 cysteine protease of the Venezuelan equine encephalitis virus
      (VEEV) is a validated antiviral drug target. Clan CN proteases contain a cysteine
      protease domain that is intimately packed with an S-adenosyl-l-methionine
      dependent RNA methyltransferase (SAM MTase) domain. Within a cleft formed at the
      interface of these two domains, the peptide substrate is thought to bind. The
      nucleophilic cysteine can be found within a conserved motif, 475NVCWAK480, which
      differs from that of papain (22CGSCWAFS29). Mutation of the motif residue, N475,
      to alanine unexpectedly produced a self-inhibited state in which the N-terminal
      residues flipped into the substrate-binding cleft. Notably, the N-terminal
      segment was not hydrolyzed-consistent with a catalytically incompetent state. The
      N475A mutation resulted in a 70-fold decrease in kcat/Km. A side chain-substrate
      interaction was predicted by the structure; the S701A mutation led to a 17-fold
      increase in Km. An Asn at the n-2 position relative to the Cys was also found in
      the coronaviral papain-like proteases/deubiquitinases (PLpro) of the SARS and
      MERS viruses, and in several papain-like human ubiquitin specific proteases
      (USP). The large conformational change in the N475A variant suggests that Asn-475
      plays an important role in stabilizing the N-terminal residues and in orienting
      the carbonyl during nucleophilic attack but does not directly hydrogen bond the
      oxyanion. The state trapped in crystallo is an unusual result of site-directed
      mutagenesis but reveals the role of this highly conserved Asn and identifies key
      substrate-binding contacts that may be exploited by peptide-like inhibitors.

PMID- 29064682
TI  - Total Syntheses of Disorazoles A1 and B1 and Full Structural Elucidation of
      Disorazole B1.
AB  - Described herein are the first total syntheses of naturally occurring antitumor
      agents disorazoles A1 and B1 and the full structural assignment of the latter.
      The syntheses were achieved through convergent strategies employing
      enantioselective constructions of the required building blocks, including a novel
      Sharpless epoxidation/enzymatic kinetic resolution of stannane-containing
      substrates that led selectively to both enantiomeric forms of an epoxy vinyl
      stannane, and a series of coupling reactions, including a Wittig reaction, a
      Suzuki coupling, a Stille coupling, a Yamaguchi esterification and a Yamaguchi
      macrolactonization.

PMID- 29064684
TI  - Molecular and Crystal Structures of Uranyl Nitrate Coordination Polymers with
      Double-Headed 2-Pyrrolidone Derivatives.
AB  - Double-headed 2-pyrrolidone derivatives (DHNRPs) were designed and synthesized as
      bridging ligands for the efficient and selective separation of UO22+ from a HNO3
      solution by precipitation. The building blocks, UO2(NO3)2 and DHNRPs, were
      successfully connected to form an infinite 1D coordination polymer. The
      solubility of [UO2(NO3)2(DHNRP)]n is no longer correlated to the hydrophobicity
      of the ligand but is exclusively governed by the ligand symmetry and packing
      efficiency. The newly designed DHNRP family can be used to establish a new spent
      nuclear fuel reprocessing scheme.

PMID- 29064685
TI  - Chemotaxis of Molecular Dyes in Polymer Gradients in Solution.
AB  - Chemotaxis provides a mechanism for directing the transport of molecules along
      chemical gradients. Here, we show the chemotactic migration of dye molecules in
      response to the gradients of several different neutral polymers. The magnitude of
      chemotactic response depends on the structure of the monomer, polymer molecular
      weight and concentration, and the nature of the solvent. The mechanism involves
      cross-diffusion up the polymer gradient, driven by favorable dye-polymer
      interaction. Modeling allows us to quantitatively evaluate the strength of the
      interaction and the effect of the various parameters that govern chemotaxis.

PMID- 29064683
TI  - Post-Translational Modifications of Protein Backbones: Unique Functions,
      Mechanisms, and Challenges.
AB  - Post-translational modifications (PTMs) dramatically enhance the capabilities of
      proteins. They introduce new functionalities and dynamically control protein
      activity by modulating intra- and intermolecular interactions. Traditionally,
      PTMs have been considered as reversible attachments to nucleophilic functional
      groups on amino acid side chains, whereas the polypeptide backbone is often
      thought to be inert. This paradigm is shifting as chemically and functionally
      diverse alterations of the protein backbone are discovered. Importantly, backbone
      PTMs can control protein structure and function just as side chain modifications
      do and operate through unique mechanisms to achieve these features. In this
      Perspective, I outline the various types of protein backbone modifications
      discovered so far and highlight their contributions to biology as well as the
      challenges in studying this versatile yet poorly characterized class of PTMs.

PMID- 29064686
TI  - Extraordinarily Stable Amyloid Fibrils Engineered from Structurally Defined beta
      Solenoid Proteins.
AB  - The self-assembly of biological molecules into ordered nanostructures is an
      attractive method for fabricating novel nanomaterials. Nucleic acid-based
      nanostructures suffer from limitations to functionalization and stability.
      Alternatively, protein-based nanostructures have advantageous chemical
      properties, but design facility lags behind that of nucleic acids. Structurally
      defined fibrils engineered from beta-solenoid proteins (BSPs) form under mild
      conditions [Peralta, M. D. R., et al. (2015) ACS Nano 9, 449-463] and are good
      candidates for novel nanomaterials because of the defined sequence-to-structure
      relationship and tunable properties. Here, the stability of two types of
      engineered fibrils was examined using circular dichroism spectroscopy,
      transmission electron microscopy, and electrophoresis. Both are stable to at
      least 90  degrees C, and one survives autoclaving. They are stable toward organic
      solvents, urea, and pH extremes. One is even stable in 2% sodium dodecyl sulfate
      with heating. The fibrils show variable resistance to proteolytic digestion: one
      is resistant to trypsin, but chymotrypsin and proteinase K degrade both. These
      results show that BSPs have excellent potential for bottom-up design of rugged,
      functional, amyloid-based nanomaterials.

PMID- 29064687
TI  - Synthesis, Structure, and Luminescence of Copper(I) Halide Complexes of Chiral
      Bis(phosphines).
AB  - For investigation of structure-property relationships in copper phosphine halide
      complexes, treatment of copper(I) halides with chiral bis(phosphines) gave
      dinuclear [Cu((R,R)-i-Pr-DuPhos)(MU-X)]2 [X = I (1), Br (2), Cl (3)], [Cu(MU
      ((R,R)-Me-FerroLANE)(MU-I)]2 (5), and [Cu((S,S)-Et-FerroTANE)(I)]2 (6),
      pentanuclear cluster Cu5I5((S,S)-Et-FerroTANE)3 (7), and the monomeric Josiphos
      complexes Cu((R,S)-CyPF-t-Bu)(I) (8) and Cu((R,S)-PPF-t-Bu)(I) (9); 1-3, 5, and 7
      9 were structurally characterized by X-ray crystallography. Treatment of iodide 1
      with AgF gave [Cu((R,R)-i-Pr-DuPhos)(MU-F)]2 (4). DuPhos complexes 1-4 emitted
      yellow-green light upon UV irradiation at room temperature in the solid state.
      This process was studied by low-temperature emission spectroscopy and density
      functional theory (DFT) calculations, which assigned the luminescence to (M +
      X)LCT (Cu2X2 to DuPhos aryl) excited states. Including Grimme's dispersion
      corrections in the DFT calculations (B3LYP-D3) gave significantly shorter Cu-Cu
      distances than those obtained using B3LYP, with the nondispersion-corrected
      calculations better matching the crystallographic data; other intramolecular
      metrics are better reproduced using B3LYP-D3. A discussion of the factors leading
      to this unusual observation is presented.

PMID- 29064689
TI  - In Situ Healing of Compromised Membranes via Polyethylenimine-Functionalized
      Silica Microparticles.
AB  - Microscale damages to membranes used in large-scale filtration processes for
      water treatment can result in severe degradation of product water quality. One
      promising technology to address this issue is in situ healing of compromised
      membranes via healing agents that are added to the feed side of a membrane system
      and seal the defect site because of increased hydraulic drag through damage site
      during filtration. We herein introduce an improved in situ membrane healing
      method using amine-functionalized silica microparticles that is effective under
      varying operating conditions, overcoming limitations faced by previous healing
      agents such as chitosan agglomerates. The silica microparticles are
      functionalized with branched polyethylenimine (PEI) molecules for efficient
      interparticle cross-linking with glutaraldehyde. The PEI-decorated silica
      microparticles (SiO2@PEI MPs) were characterized using scanning electron
      microscopy, dynamic light scattering, and zeta potential analysis. This study
      investigates the selective deposition of the SiO2@PEI MPs on the damage area
      using confocal laser scanning microscopy under variable cross-flow rate (0.5-2.0
      L/min) and flushing time (10 to 30 min) conditions. The in situ healing technique
      recovered the particle rejection of compromised membranes to 99.1% of the
      original membrane's performance without any flux decline. The results of this
      study show that the use of SiO2@PEI MPs is a promising and practical approach to
      ensure membrane process integrity.

PMID- 29064688
TI  - Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and
      Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and
      Simpler Antibacterial Agents.
AB  - An improved and enantioselective total synthesis of antibiotic CJ-16,264 through
      a practical kinetic resolution and an iodolactonization reaction to form the iodo
      pyrrolizidinone fragment of the molecule is described. A series of racemic and
      enantiopure analogues of CJ-16,264 was designed and synthesized through the
      developed synthetic technologies and tested against drug-resistant bacterial
      strains. These studies led to interesting structure-activity relationships and
      the identification of a number of simpler, and yet equipotent, or even more
      potent, antibacterial agents than the natural product, thereby setting the
      foundation for further investigations in the quest for new anti-infective drugs.

PMID- 29064690
TI  - Defining Functional Structured RNA inside Living Cells.

PMID- 29064691
TI  - Structure- and Potential-Dependent Cation Effects on CO Reduction at Copper
      Single-Crystal Electrodes.
AB  - The complexity of the electrocatalytic reduction of CO to CH4 and C2H4 on copper
      electrodes prevents a straightforward elucidation of the reaction mechanism and
      the design of new and better catalysts. Although structural and electrolyte
      effects have been separately studied, there are no reports on structure-sensitive
      cation effects on the catalyst's selectivity over a wide potential range.
      Therefore, we investigated CO reduction on Cu(100), Cu(111), and
      Cu(polycrystalline) electrodes in 0.1 M alkaline hydroxide electrolytes (LiOH,
      NaOH, KOH, RbOH, CsOH) between 0 and -1.5 V vs RHE. We used online
      electrochemical mass spectrometry and high-performance liquid chromatography to
      determine the product distribution as a function of electrode structure, cation
      size, and applied potential. First, cation effects are potential dependent, as
      larger cations increase the selectivity of all electrodes toward ethylene at E > 
      0.45 V vs RHE, but methane is favored at more negative potentials. Second, cation
      effects are structure-sensitive, as the onset potential for C2H4 formation
      depends on the electrode structure and cation size, whereas that for CH4 does
      not. Fourier Transform infrared spectroscopy (FTIR) and density functional theory
      help to understand how cations favor ethylene over methane at low overpotentials
      on Cu(100). The rate-determining step to methane and ethylene formation is CO
      hydrogenation, which is considerably easier in the presence of alkaline cations
      for a CO dimer compared to a CO monomer. For Li+ and Na+, the stabilization is
      such that hydrogenated dimers are observable with FTIR at low overpotentials.
      Thus, potential-dependent, structure-sensitive cation effects help steer the
      selectivity toward specific products.

PMID- 29064692
TI  - NMR Study of Solvation Effect on the Geometry of Proton-Bound Homodimers of
      Increasing Size.
AB  - Hydrogen bond geometries in the proton-bound homodimers of quinoline and acridine
      derivatives in an aprotic polar solution have been experimentally studied using
      1H NMR at 120 K. The reported results show that an increase of the dielectric
      permittivity of the medium results in contraction of the N...N distance. The
      degree of contraction depends on the homodimer's size and its substituent
      specific solvation features. Neither of these effects can be reproduced using
      conventional implicit solvent models employed in computational studies. In
      general, the N...N distance in the homodimers of pyridine, quinoline, and
      acridine derivatives decreases in the sequence gas phase > solid state > polar
      solvent.

PMID- 29064693
TI  - Synthesis of Quaternary-Substituted Thiazolines via Halocyclization of S-Allyl
      Thioimidate Salts.
AB  - An efficient synthesis of S-allyl thioimidate hydrobromide salts via coupling of
      thioamides with allyl bromide derivatives is described. A range of mono-, di-,
      and trisubstituted olefins as well as alkyl- and arylthioamides with variations
      in electronics are tolerated. A rapid anti-diastereoselective halocyclization of
      these salts provides a variety of substituted alkyl- and arylthiazolines. Initial
      development of an efficient enantioselective synthesis of quaternary-substituted
      thiazolines through the organo-catalyzed halocyclization of sulfonate thioimidate
      salts is also described.

PMID- 29064695
TI  - Polar Molecular Ordering in the NX Phase of Bimesogens and Enantiotopic
      Discrimination in the NMR Spectra of Rigid Prochiral Solutes.
AB  - The potential of mean torque governing the orientational ordering of prochiral
      solutes in the two nematic phases (N and NX) formed by certain classes of
      symmetric achiral bimesogens is formulated and used for the analysis of existing
      NMR measurements on solutes of various symmetries dissolved in the two phases.
      Three distinct attributes of the solvent phase, namely polarity of the
      orientational ordering, chirality of the constituent molecules, and spatial
      modulation of the local director, are identified as underlying three possible
      mechanisms for the generation of chiral asymmetry in the low temperature nematic
      phase (NX). The role and quantitative contribution of each mechanism to
      enantiotopic discrimination in the NX phase are presented and compared with the
      case of the conventional chiral nematic phase (N*). It is found that polar
      ordering is essential for the appearance of enantiotopic discrimination in small
      rigid solutes dissolved in the NX phase and that such discrimination is
      restricted to solutes belonging to the point group symmetries Cs and C2v.

PMID- 29064694
TI  - Ligand-Substrate Dispersion Facilitates the Copper-Catalyzed Hydroamination of
      Unactivated Olefins.
AB  - The current understanding of ligand effects in transition metal catalysis is
      mostly based on the analysis of catalyst-substrate through-bond and through-space
      interactions, with the latter commonly considered to be repulsive in nature. The
      dispersion interaction between the ligand and the substrate, a ubiquitous type of
      attractive noncovalent interaction, is seldom accounted for in the context of
      transition-metal-catalyzed transformations. Herein we report a computational
      model to quantitatively analyze the effects of different types of catalyst
      substrate interactions on reactivity. Using this model, we show that in the
      copper(I) hydride (CuH)-catalyzed hydroamination of unactivated olefins, the
      substantially enhanced reactivity of copper catalysts based on bulky bidentate
      phosphine ligands originates from the attractive ligand-substrate dispersion
      interaction. These computational findings are validated by kinetic studies across
      a range of hydroamination reactions using structurally diverse phosphine ligands,
      revealing the critical role of bulky P-aryl groups in facilitating this process.

PMID- 29064696
TI  - Camellianols A-G, Barrigenol-like Triterpenoids with PTP1B Inhibitory Effects
      from the Endangered Ornamental Plant Camellia crapnelliana.
AB  - Seven new naturally occurring barrigenol-like compounds, camellianols A-G (1-7),
      and 10 known triterpenoids were isolated from the twigs and leaves of the
      cultivated endangered ornamental plant Camellia crapnelliana. According to the
      ECD octant rule for saturated cyclohexanones, the absolute configurations of
      camellianols D (4) and E (5) were defined. The backbones of the remaining new
      isolates are assumed to have the same absolute configuration as compounds 4, 5,
      and harpullone (12). Compounds 2, 3, 9, 10, 13, and 16 exhibited inhibitory
      effects on the protein tyrosine phosphatase 1B (PTP1B) enzyme, with IC50 values
      less than 10 MUM.

PMID- 29064697
TI  - Photosystem II Acts as a Spin-Controlled Electron Gate during Oxygen Formation
      and Evolution.
AB  - The oxygen evolution complex (OEC) of photosystem II (PSII) is intrinsically more
      active than any synthetic alternative for the oxygen evolution reaction (OER). A
      crucial question to solve for the progress of artificial photosynthesis is to
      understand the influential interactions during water oxidation in PSII. We study
      the principles of interatomic electron transfer steps in OER, with emphasis on
      exchange interactions, revealing the influence of delocalizing ferromagnetic spin
      potentials during the catalytic process. The OEC is found to be an exchange
      coupled mixed-valence electron-spin acceptor where its orbital physics determine
      the unique activity of PSII. The two unpaired electrons needed in the triplet O2
      molecule interact with the high spin state of the catalyst via exchange
      interactions; the optimal ferromagnetic catalyst and the resulting radical
      intermediates are spin paired. As a result, the active center of the CaMn4O5
      cofactor, stimulated by the driving potential provided by photons, works as a
      spin valve to accelerate the formation and release of O2 from diamagnetic H2O.

PMID- 29064698
TI  - Nature and Hierarchy of Noncovalent Interactions in Gas-Phase Binary Complexes of
      Indole and Benzimidazole with Ethers.
AB  - Hierarchy among the weak noncovalent interactions such as van der Waals,
      electrostatic, hydrogen bonding, etc. dictates the secondary and tertiary
      structures of proteins as well as their interactions with various ligands. In
      this work, we investigate the competition between conventional (N-H...O) hydrogen
      bonds, unconventional (C-H...O) hydrogen bonds, and the van der Waals interaction
      in the model compounds of the chromophores of the amino acids, tryptophan, and
      histidine. These include indole (IND), benzimidazole (BIM), and its N-methylated
      analog (N-methylbenzimidazole, MBIM), which present multiple docking sites. The
      binary complexes of these molecules with ethers (dimethyl ether, diethyl ether,
      and tetrahydrofuran), which possess high proton affinity but lack acidic protons
      (thereby only act as hydrogen bond acceptors), are investigated. The complexes
      are formed in a supersonic jet and jointly studied by electronic and vibrational
      spectroscopy as well as quantum chemical calculations. Only the N-H...O bound
      structures are observed for the complexes of IND and BIM with ethers, although
      computations predict reasonably competent C-H...O type of structures. Remarkably,
      IND and BIM produce three (N-H...O) conformers with Me2O but single conformers
      with Et2O and THF. In the case of MBIM, which lacks a conventional hydrogen bond
      donor, no evidence for C(2)-H...O hydrogen bonds is seen; instead, the complexes
      are found to be bound purely by van der Waals interactions. The results indicate
      that strong N-H...O and even weak van der Waals interactions are
      thermodynamically favored over C(2)-H...O bound structures in these binary gas
      phase complexes.

PMID- 29064699
TI  - mRNA-Sequencing Analysis Reveals Transcriptional Changes in Root of Maize
      Seedlings Treated with Two Increasing Concentrations of a New Biostimulant.
AB  - Biostimulants are a wide range of natural or synthetic products containing
      substances and/or microorganisms that can stimulate plant processes to improve
      nutrient uptake, nutrient efficiency, tolerance to abiotic stress, and crop
      quality ( http://www.biostimulants.eu/ , accessed September 27, 2017). The use of
      biostimulants is proposed as an advanced solution to face the demand for
      sustainable agriculture by ensuring optimal crop performances and better
      resilience to environment changes. The proposed approach is to predict and
      characterize the function of natural compounds as biostimulants. In this
      research, plant growth assessments and transcriptomic approaches are combined to
      investigate and understand the specific mode(s) of action of APR, a new product
      provided by the ILSA group (Arzignano, Vicenza). Maize seedlings (B73) were kept
      in a climatic chamber and grown in a solid medium to test the effects of two
      different combinations of the protein hydrolysate APR (A1 and A1/2). Data on root
      growth evidenced a significant enhancement of the dry weight of both roots and
      root/shoot ratio in response to APR. Transcriptomic profiles of lateral roots of
      maize seedlings treated with two increasing concentrations of APR were studied by
      mRNA-sequencing analysis (RNA-seq). Pairwise comparisons of the RNA-seq data
      identified a total of 1006 differentially expressed genes between treated and
      control plants. The two APR concentrations were demonstrated to affect the
      expression of genes involved in both common and specific pathways. On the basis
      of the putative function of the isolated differentially expressed genes, APR has
      been proposed to enhance plant response to adverse environmental conditions.

PMID- 29064700
TI  - Critical Role of the Spacer Length of Gemini Surfactants on the Formation of
      Ionic Liquid Crystals and Thermotropic Behavior.
AB  - Numerous reports have shown that the self-assembling properties of 12-s-12
      bis(quaternary ammonium) gemini surfactants in aqueous solution are significantly
      influenced by s, the number of methylene groups in the covalent spacer. However,
      the role played by s on the phase behavior of the single compounds has not been
      investigated in a similarly systematic way. Here, we report on the thermotropic
      phase behavior of the anhydrous compounds with s = 2-6, 8, 10, and 12, resorting
      to differential scanning calorimetry (DSC), polarized light microscopy (PLM), and
      X-ray diffraction (XRD). All of the compounds show a stepwise melting behavior,
      decomposing at 200  degrees C. As the spacer length increases, nonmonotonic
      trends are observed for the thermodynamic parameters of the thermotropic phase
      transitions, mesophase formation, and solid-state d00l spacings. In particular,
      the number and type of mesophases (ordered smectic phases and/or fluid smectic
      liquid crystals) depend critically on s. Further, upon heating molecules with s <
      8 decompose before the liquid phase, while those with long spacers, s = 8-12,
      reach the isotropization (clearing) temperature, hence forming both ionic liquid
      crystals and ionic liquid phases. We demonstrate that the melting behavior and
      type of ionic mesophases formed by gemini molecules can be usefully manipulated
      by a simple structural parameter like the length of the covalent linker.

PMID- 29064701
TI  - Support for a Dioxyallyl Cation in the Mechanism Leading to (-)-Levoglucosenone.
AB  - Levoglucosenone (LGO) is the major product formed when cellulose is pyrolyzed in
      the presence of acid at temperatures between 170 and 350  degrees C. The current
      intense interest in biomass conversion has led to a number of reports on its
      preparation; however, there is still uncertainty on the mechanism leading to LGO.
      We propose a new mechanism which involves a C2-C1 hydride shift followed by
      intramolecular trapping of a dioxyallyl cation. The reaction has been modeled
      using DFT calculations from the known LGO precursors levoglucosan and 1,4:3,6
      dianhydro-alpha-D-glucopyranose to a common intermediate with calculated barriers
      of 10.6 and 13.5 kcal.mol-1, respectively. A discussion of the literature on the
      formation of LGO from late pathway intermediates is also provided.

PMID- 29064702
TI  - Novel Potassium Polynitrides at High Pressures.
AB  - Polynitrogen compounds have attracted great interest due to their potential
      applications as high energy density materials. Most recently, a rich variety of
      alkali polynitrogens (RxNy; R = Li, Na, and Cs) have been predicted to be stable
      at high pressures and one of them, CsN5 has been recently synthesized. In this
      work, various potassium polynitrides are investigated using first-principles
      crystal structure search methods. Several novel molecular crystals consisting of
      N4 chains, N5 rings, and N6 rings stable at high pressures are discovered. In
      addition, an unusual nitrogen-rich metallic crystal with stoichiometry K2N16
      consisting of a planar two-dimensional extended network of nitrogen atoms
      arranged in fused 18 atom rings is found to be stable above 70 GPa. An
      appreciable electron transfer from K to N atoms is responsible for the appearance
      of unexpected chemical bonding in these crystals. The thermodynamic stability and
      high pressure phase diagram is constructed. The electronic and vibrational
      properties of the layered polynitrogen K2N16 compound are investigated, and the
      pressure-dependent IR spectrum is obtained to assist in experimental discovery of
      this new high-nitrogen content material.

PMID- 29064703
TI  - Unwinding Induced Melting of Double-Stranded DNA Studied by Free Energy
      Simulations.
AB  - DNA unwinding plays a major role in many biological processes, such as
      replication, transcription, and repair. It can lead to local melting and strand
      separation and can serve as a key mechanism to promote access to the separate
      strands of a double-stranded DNA. While DNA unwinding has been investigated
      extensively by DNA cyclization and single-molecule studies on a length-scale of
      kilo base pairs, it is neither fully understood at the base pair level nor at the
      level of molecular interactions. By employing a torque acting on the termini of
      DNA oligonucleotides during molecular dynamics free energy simulations, we
      locally unwind the central part of a DNA beyond an elastic (harmonic) regime. The
      simulations reproduce experimental results on the twist elasticity in the
      harmonic regime (characterized by a mostly quadratic free energy change with
      respect to changes in twist) and a deformation up to 7 degrees  was found as a
      limit of the harmonic response. Beyond this limit the free energy increase per
      twist change dropped dramatically coupled to local base pair disruptions and
      significant deformation of the nucleic acid backbone structure. Restriction of
      the DNA bending flexibility resulted in a stiffer harmonic response and an
      earlier onset of the anharmonic response. Whereas local melting with a complete
      disruption of base pairing and flipping of nucleotides was observed in case of an
      AT rich central segment strong backbone changes and changes in the stacking
      arrangements were observed in case of a GC rich segment. Unrestrained MD
      simulations starting from locally melted DNA reformed regular B-DNA after 50-300
      ns simulation time. The simulations may have important implications for
      understanding DNA recognition processes coupled with significant structural
      alterations.

PMID- 29064704
TI  - Fingerprints of Both Watson-Crick and Hoogsteen Isomers of the Isolated (Cytosine
      Guanine)H+ Pair.
AB  - Gas phase protonated guanine-cytosine (CGH+) pair was generated using an
      electrospray ionization source from solutions at two different pH (5.8 and 3.2).
      Consistent evidence from MS/MS fragmentation patterns and differential ion
      mobility spectra (DIMS) point toward the presence of two isomers of the CGH+
      pair, whose relative populations depend strongly on the pH of the solution. Gas
      phase infrared multiphoton dissociation (IRMPD) spectroscopy in the 900-1900 cm-1
      spectral range further confirms that the Watson-Crick isomer is preferentially
      produced (91%) at pH = 5.8, while the Hoogsteen isomer predominates (66%) at pH =
      3.2). These fingerprint signatures are expected to be useful for the development
      of new analytical methodologies and to trigger isomer selective photochemical
      studies of protonated DNA base pairs.

PMID- 29064705
TI  - Breakdown of Far-Field Raman Selection Rules by Light-Plasmon Coupling
      Demonstrated by Tip-Enhanced Raman Scattering.
AB  - We present an experimental study on the near-field light-matter interaction by
      tip-enhanced Raman scattering (TERS) with polarized light in three different
      materials: germanium-doped gallium nitride (GaN), graphene, and carbon nanotubes.
      We investigate the dependence of the TERS signal on the incoming light
      polarization and on the sample carrier concentration, as well as the Raman
      selection rules in the near-field. We explain the experimental data with a
      tentative quantum mechanical interpretation, which takes into account the role of
      plasmon polaritons, and the associated evanescent field. The driving force for
      the breakdown of the classical Raman selection rules in TERS is caused by photon
      tunneling through the perturbation of the evanescent field, with the consequent
      polariton annihilation. Predictions based on this quantum mechanical approach are
      in good agreement with the experimental data, which are shown to be independent
      of incoming light polarization, leading to new Raman selection rules for TERS.

PMID- 29064706
TI  - Charging Poly(methyl Methacrylate) Latexes in Nonpolar Solvents: Effect of
      Particle Concentration.
AB  - The electrophoresis of a well-established model system of charged colloids in
      nonpolar solvents has been studied as a function of particle volume fraction at
      constant surfactant concentration. Dispersions of poly(12-hydroxystearic acid)
      stabilized poly(methyl methacrylate) (PMMA) latexes in dodecane were prepared
      with added Aerosol OT surfactant as the charging agent. The electrophoretic
      mobility (MU) of the PMMA latexes is found to decrease with particle
      concentration. The particles are charged by a small molecule charging agent (AOT)
      at finite concentration, and this makes the origin of this decrease in MU
      unclear. There are two suggested explanations. The decrease could either be due
      to the reservoir of available surfactant being exhausted at high particle
      concentrations or the interactions between the charged particles at high particle
      number concentrations. Contrast-variation small-angle neutron scattering
      measurements of PMMA latexes and deuterated AOT-d34 surfactant in latex core
      contrast-matched solvent were used to study the former, and electrokinetic
      modeling was used to study the latter. As the same amount of AOT-d34 is found to
      be incorporated with the latexes at all volume fractions, the solvodynamic and
      electrical interactions between particles are determined to be the explanation
      for the decrease in mobility. These measurements show that, for small latexes,
      there are interactions between the charged particles at all accessible particle
      volume fractions and that it is necessary to account for this to accurately
      determine the electrokinetic zeta potential.

PMID- 29064707
TI  - l-Carnosine-Derived Fmoc-Tripeptides Forming pH-Sensitive and Proteolytically
      Stable Supramolecular Hydrogels.
AB  - A series of beta-amino acid containing tripeptides has been designed and
      synthesized in order to develop oligopeptide-based, thermoreversible, pH
      sensitive, and proteolytically stable hydrogels. The Fmoc [N-(fluorenyl-9
      methoxycarbonyl)]-protected tripeptides were found to produce hydrogels in both
      pH 7 and 2 buffers at a very low concentration (<0.2% w/v). It has been shown
      that the Fmoc group plays an important role in the gelation process. Also a
      dependence of gelation ability on hydrophobicity of the side chain of the Fmoc
      protected alpha-amino acid was observed. The effect of the addition of inorganic
      salts on the gelation process was investigated as well. Spectroscopic studies
      indicated formation of J-aggregates through pi-pi stacking interactions between
      Fmoc groups in solution as well as in the gel state. In the gel phase, these self
      assembling tripeptides form long interconnected nanofibrils leading to the
      formation of 3-dimensional network structure. The hydrogels were characterized by
      various techniques, including field emission electron microscopy, transmission
      electron microscopy, atomic force microscopy, rheology, Fourier transform IR,
      circular dichroism (CD), and wide-angle X-ray diffraction (WAXD) spectroscopy.
      The CD studies and WAXD analyses show an antiparallel beta-sheet structure in the
      gel state. l-Phenylalanine and l-tyrosine containing tripeptides formed helical
      aggregates with handedness opposite to those containing l-valine and l-leucine
      residues. The mechanical stability of the hydrogels was found to depend on the
      hydrophobicity of the side chain of the tripeptide as well as on the pH of the
      solution. Also, the tripeptides exhibit in vitro proteolytic stability against
      proteinase K enzyme.

PMID- 29064708
TI  - Oil-in-Water Emulsion Templated and Crystallization-Driven Self-Assembly
      Formation of Poly(l-lactide)-Polyoxyethylene-Poly(l-lactide) Fibers.
AB  - A molecular solution of an amphiphilic block copolymer may act as an oil phase by
      dispersing into an aqueous micellar system of small-molecular surfactant, forming
      oil-in-water (O/W) emulsion droplets. In this paper, an as-synthesized triblock
      copolymer poly(l-lactide)-polyoxyethylene-poly(l-lactide) (PLLA-PEO-PLLA) was
      dissolved in tetrahydrofuran (THF) and then added to an aqueous micellar solution
      of nonaethylene glycol monododecyl ether (AEO-9), forming initially coalescent
      O/W emulsion droplets in the size range of 35 nm-1.3 MUm. Along with gradual
      volatilization of THF and simultaneous concentration of PLLA-PEO-PLLA molecules,
      the amphiphilic copolymer backbones themselves experience solution-based self
      assembly, forming inverted core-corona aggregates within an oil-phase domain.
      Anisotropic coalescence of adjacent O/W emulsion droplets occurs, accompanied by
      further volatilization of THF. The hydrophilic block crystallization of core
      forming PEOs and the hydrophobic chain stretch of corona-forming PLLAs together
      induce the intermediate formation of rod-like architectures with an average
      diameter of 300-800 nm, and this leads to a large-scale deposition of the
      triblock copolymer fibers with an average diameter of ~2.0 MUm. Consequently,
      this strategy could be of general interest in the self-assembly formation of
      amphiphilic block copolymer fibers and could also provide access to aqueous
      solution crystallization of hydrophilic segments of these copolymers.

PMID- 29064709
TI  - Organocatalytic Phosphonylation of in Situ Formed o-Quinone Methides.
AB  - A new class of Bronsted acid catalysts based on N-heterocyclic phosphorodiamidic
      acids (NHPAs) has been developed. The NHPA catalyst promotes phospha-Michael
      addition reaction of trialkylphosphites to in situ generated ortho-quinone
      methides (o-QMs) for the construction of diaryl phosphonates in moderate to
      excellent yields with 1.5 mol % catalyst. Diastereoselective synthesis of P
      chiral phosphinate esters is achieved with the use of dialkyl phenylphosphonites.

PMID- 29064710
TI  - Synthesis of Tetrahydropyridine Derivatives through a Reaction of 1,6-Enynes,
      Sulfur Dioxide, and Aryldiazonium Tetrafluoroborates.
AB  - Sulfonated tetrahydropyridine derivatives are accessed through a radical reaction
      of 1,6-enynes, sulfur dioxide, and aryldiazonium tetrafluoroborates under mild
      conditions. Sulfonated pyrrolidine can be generated when terminal alkyne is used
      as the substrate. This reaction proceeds efficiently in dichloroethane without
      the addition of any catalysts or additives, providing sulfonated
      tetrahydropyridine derivatives in moderate to good yields. During this
      transformation, aryldiazonium tetrafluoroborates cooperate with DABCO.(SO2)2
      leading to sulfonyl radicals, which initiate the radical cyclization process. Two
      molecules of aryldiazonium tetrafluoroborates are involved in the reaction.

PMID- 29064711
TI  - Schizophrenic Diblock-Copolymer-Functionalized Nanoparticles as Temperature
      Responsive Pickering Emulsifiers.
AB  - Stimuli-responsive pickering emulsions have received considerable attention in
      recent years, and the utilization of temperature as a stimulus has been of
      particular interest. Previous efforts have led to responsive systems that enable
      the formation of stable emulsions at room temperature, which can subsequently be
      triggered to destabilize with an increase in temperature. The development of a
      thermoresponsive system that exhibits the opposite response, however, i.e., one
      that can be triggered to form stable emulsions at elevated temperatures and
      subsequently be induced to phase separate at lower temperatures, has so far been
      lacking. Here, we describe a system that accomplishes this goal by leveraging a
      schizophrenic diblock copolymer that exhibits both an upper and a lower critical
      solution temperature. The diblock copolymer was conjugated to 20 nm silica
      nanoparticles, which were subsequently demonstrated to stabilize O/W emulsions at
      65  degrees C and trigger phase separation upon cooling to 25  degrees C. The
      effects of particle concentration, electrolyte concentration, and polymer
      architecture were investigated, and facile control of emulsion stability was
      demonstrated for multiple oil types. Our approach is likely to be broadly
      adaptable to other schizophrenic diblock copolymers and find significant utility
      in applications such as enhanced oil recovery and liquid-phase heterogeneous
      catalysis, where stable emulsions are desired only at elevated temperatures.

PMID- 29064712
TI  - Superhydrophobicity from the Inside.
AB  - The nature of trapped air on submersed ultra-water-repellent interfaces has been
      investigated. These gaseous layers (plastrons) can last from hours to, in some
      examples such as the Salvinia molesta fern, months. The interface of submerged
      superhydrophobic surfaces with carefully controlled micropatterned surface
      roughness has been probed using synchrotron-based high-resolution X-ray phase
      tomography. This technique looks in situ, through the aqueous/gas interface in
      three dimensions. Long-term plastron stability appears to correlate with the
      appearance of scattered microdroplets <20 MUm in diameter that are sandwiched
      within the 30 MUm thick gaseous interfacial layer. These microdroplets are
      centered on defects or damaged sections within the substrate surface
      approximately 20-50 MUm apart. Such irregularities represent heterogeneous
      micro/nano-hierarchical structures with varying surface structures and chemistry.
      The stability of microdroplets is governed by a combination of electrostatic
      repulsion, contact angle limitations, and a saturated vapor pressure, the latter
      of which reduces the rate of diffusion of gas out of the air layer, thus
      increasing underwater longevity. Homogenous surfaces exhibiting purely nano- or
      micro-regularity do not support such microdroplets, and, as a consequence,
      plastrons can disappear in <20 h compared with >160 h for surfaces with scattered
      microdroplets. Such behavior may be a requirement for long-term nonwetting in any
      system.

PMID- 29064713
TI  - Morphological Transition in Fatty Acid Self-Assemblies: A Process Driven by the
      Interplay between the Chain-Melting and Surface-Melting Process of the Hydrogen
      Bonds.
AB  - In surfactant systems, the major role of the nature of the counterion in the
      surfactant behavior is well-known. However, the effect of the molar ratio between
      the surfactant and its counterion is less explored in the literature. We
      investigated the effect of the molar ratio (R) between 12-hydroxystearic acid (12
      HSA) and various alkanolamines as a function of the temperature in aqueous
      solution from the molecular scale to the mesoscale. By coupling microscopy
      techniques and small-angle neutron scattering, we showed that 12-HSA self
      assembled into multilamellar tubes and transitioned into micelles at a precise
      temperature. This temperature transition depended on both the molar ratio and the
      alkyl chain length of the counterion and could be precisely tuned from 20 to 75 
      degrees C. This thermal behavior was investigated by differential scanning
      calorimetry and wide-angle X-ray scattering. We highlighted that the transition
      at the supramolecular scale between tubes and micelles came from two different
      mechanisms at the molecular scale as a function of the molar ratio. At low R,
      with an excess of counterion, the transition came from the chain-melting
      phenomenon. At high R, with an excess of 12-HSA, the transition came from both
      the chain-melting process and the surface-melting process of the hydrogen bonds.
      At the mesoscale, this transition of supramolecular assemblies from tubes to
      micelles delimited a regime of high bulk viscosity, with a regime of low
      viscosity.

PMID- 29064715
TI  - Driving Force for Spontaneous Perforation of Bilayers Formed by Ionic Amphiphiles
      in Aqueous Salt.
AB  - Spontaneous perforation of amphiphilic membranes is important in both living
      matter and technology because of an impact on functions of biological membranes
      and shape transitions of self-assembling structures. Nevertheless, no definite
      molecular mechanism has been established so far even for simple ionic surfactant
      systems. We show that spontaneous perforation of a bilayer formed by an ionic
      amphiphile is driven by electrostatics. Creation of large pores with a concave
      convex geometry of the rim is promoted by lower electrostatic free energy than
      that for a flat nonperforated bilayer. The opposite effect comes from the
      elasticity of the hydrocarbon tails of the amphiphile that prefer flat geometry
      of a nonperforated bilayer. The balance between electrostatics and tail
      deformation controls the appearance of pores; this balance is modulated by added
      salt that screens the electrostatic interactions. We illustrate the proposed
      mechanism with the aid of classical aggregation model that has been extended by
      including an analytical description of the electrostatic contribution for the
      toroidal rim of a pore. Numerical solution of the linearized Poisson-Boltzmann
      equation confirms the role of electrostatic forces in formation of pores. For the
      ionic surfactants of CnTAB family, we predict shape transitions including bilayer
      perforations and formation of branched micellar networks induced by changing
      salinity or temperature and demonstrate the effect of surfactant's molecular
      parameters on these transitions.

PMID- 29064714
TI  - Gated Mesoporous Silica Nanocarriers for a "Two-Step" Targeted System to Colonic
      Tissue.
AB  - Colon targeted drug delivery is highly relevant not only to treat colonic local
      diseases but also for systemic therapies. Mesoporous silica nanoparticles (MSNs)
      have been demonstrated as useful systems for controlled drug release given their
      biocompatibility and the possibility of designing gated systems able to release
      cargo only upon the presence of certain stimuli. We report herein the preparation
      of three gated MSNs able to deliver their cargo triggered by different stimuli
      (redox ambient (S1), enzymatic hydrolysis (S2), and a surfactant or being in
      contact with cell membrane (S3)) and their performance in solution and in vitro
      with Caco-2 cells. Safranin O dye was used as a model drug to track cargo fate.
      Studies of cargo permeability in Caco-2 monolayers demonstrated that
      intracellular safranin O levels were significantly higher in Caco-2 monolayers
      when using MSNs compared to those of free dye. Internalization assays indicated
      that S2 nanoparticles were taken up by cells via endocytosis. S2 nanoparticles
      were selected for in vivo tests in rats. For in vivo assays, capsules were filled
      with S2 nanoparticles and coated with Eudragit FS 30 D to target colon. The
      enteric coated capsule containing the MSNs was able to deliver S2 nanoparticles
      in colon tissue (first step), and then nanoparticles were able to deliver
      safranin O inside the colonic cells after the enzymatic stimuli (second step).
      This resulted in high levels of safranin O in colonic tissue combined with low
      dye levels in plasma and body tissues. The results suggested that this
      combination of enzyme-responsive gated MSNs and enteric coated capsules may
      improve the absorption of drugs in colon to treat local diseases with a reduction
      of systemic effects.

PMID- 29064716
TI  - Copper-Catalyzed Enantioselective Cyclopropanation of Internal Olefins with
      Diazomalonates.
AB  - The first enantioselective copper catalyzed cyclopropanation of internal olefins
      with diazomalonates is reported. This process provides a new method for the
      synthesis of chiral 1,1-cyclopropane diesters. With a chiral bi-side arm
      bisoxazoline-copper(I) complex, the reaction performed well over a series of
      substrates, giving the desired products in good yields (up to 95%) and excellent
      enantioselectivities (90-95% ee).

PMID- 29064717
TI  - Synthesis of Alfaprostol and PGF2alpha through 1,4-Addition of an Alkyne to an
      Enal Intermediate as the Key Step.
AB  - The veterinary drug Alfaprostol and prostaglandin PGF2alpha have been synthesized
      in just nine steps. The strategy involved the conjugate addition of an alkyne to
      a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction
      of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest
      synthesis reported to date. For PGF2alpha, this approach improved our previous
      route by making the 1,4-addition and ozonolysis more operationally simple.

PMID- 29064718
TI  - Switchable Chemoselectivity for Organocatalytic, Asymmetric Malononitrile
      Addition to ortho-Formyl Chalcones.
AB  - Chemoselective 1,2- and 1,4-addition of malononitriles to ortho-formyl chalcones
      using cinchona alkaloid based bifunctional chiral organocatalysts has been shown
      by tuning the electronic nature of the malononitriles. Alkyl (hard)
      malononitriles undergo an asymmetric 1,2-addition followed by oxa-Michael
      reaction cascade to afford 1,3-disubstituted isobenzofurans with high enantio-
      and diastereoselectivity. Aryl (soft) malononitriles proceed through 1,4-addition
      followed by an aldol reaction cascade to provide indanols, having three
      consecutive stereocenters, in good yields and with good to excellent enantio- and
      diastereoselectivites.

PMID- 29064719
TI  - Visible-Light-Mediated Radical Arylation of Anilines with Acceptor-Substituted
      (Hetero)aryl Halides.
AB  - A visible-light-mediated, catalyst-free, direct (hetero)arylation of anilines
      with mild reaction conditions has been developed. The formation of a donor
      acceptor complex between electron-withdrawing substituted (hetero)aryl halides
      and anilines allows, under blue LED irradiation, the synthesis of ortho and para
      (hetero)arylated anilines in moderate to good yields. The reaction has a high
      functional group tolerance. Spectroscopic studies confirmed the donor-acceptor
      complex formation between aniline and aryl halide.

PMID- 29064720
TI  - Controllable Stereoselective Synthesis of (Z)- and (E)-Homoallylic Alcohols Using
      a Palladium-Catalyzed Three-Component Reaction.
AB  - Diastereoselective synthesis of (Z)- and (E)-homoallylic alcohols using a Pd
      catalyzed three-component reaction of 3-(pinacolatoboryl)allyl benzoates,
      aldehydes, and aryl stannanes was developed, which provides an alternative method
      for the allylboration of aldehydes using alpha,gamma-diaryl-substituted
      allylboronates. Both sets of reaction conditions enable access to either (Z)- or
      (E)-homoallylic alcohols with good to high alkene stereocontrol. The present
      method showed good functional group compatibility and generality. Efficient
      chirality transfer reactions to afford enantioenriched (Z)- and (E)-homoallylic
      alcohols were also achieved.

PMID- 29064721
TI  - Asymmetric Formal [3 + 2]-Cycloaddition of Azomethine Imines with Azlactones To
      Synthesize Bicyclic Pyrazolidinones.
AB  - An efficient enantioselective formal [3 + 2]-cycloaddition of azomethine imines
      with azlactones has been realized by using a chiral bifunctional bisguanidinium
      hemisalt as the catalyst. Optically active bicyclic pyrazolidinone compounds were
      generated under mild reaction conditions in high yields (up to 99%) with good dr
      (up to 88:12) and excellent ee values (up to 99%). This simple and efficient
      strategy provides a method to construct biologically important chiral
      tetrahydropyrazolo[1,2-a]pyrazole-1,7-dione derivatives bearing vicinal aza
      quaternary and tertiary carbon centers.

PMID- 29064723
TI  - Computing circadian misalignment: Why not combine sleep timing and duration to
      assess accumulated sleep deficiency?

PMID- 29064722
TI  - Palladium-Catalyzed Synthesis of 1H-Indenes and Phthalimides via Isocyanide
      Insertion.
AB  - A new and versatile multicomponent domino strategy has been developed for the
      synthesis of a series of 1H-indene and phthalimide derivatives from simple and
      readily available starting materials. This process operating under mild
      conditions shows a broad substrate scope with moderate to excellent yields.

PMID- 29064724
TI  - The effects of tackle height on inertial loading of the head and neck in Rugby
      Union: A multibody model analysis.
AB  - OBJECTIVE: There is evidence of chronic injury to the head-and-neck region of
      Rugby Union players. The aim of this study was to use multibody simulations to
      examine the effects of tackle height on both Tackler and Ball Carrier head
      kinematics and neck dynamics. RESEARCH DESIGN: Quantitative Exploratory Study
      Methods and procedures: 45 front-on shoulder tackles with no direct contact to
      the head/neck were simulated with the MADYMO pedestrian model and used to assess
      differences between upper body tackles and lower body tackles. The average
      resultant head linear and angular accelerations as well as neck forces and
      moments were assessed. MAIN OUTCOMES AND RESULTS: Much higher Ball Carrier head
      kinematic values and neck loading were predicted for upper body tackles compared
      to lower body tackles, and principal findings were unaffected by a sensitivity
      analysis. Tackler results were less straightforward and trends were influenced by
      the sensitivity analysis for muscle activation. CONCLUSION: Although further
      model validation is required, the results of this study indicate the need for
      further research on tackle heights and inertial head-and-neck loading in the
      tackle phase of play in Rugby Union.

PMID- 29064725
TI  - alpha2-Adrenoceptor-ir neurons' density changes after single dose of clonidine
      and yohimbine administration in the hippocampus of male rat.
AB  - OBJECTIVE: Despite the important role of alpha2-adrenoceptors in pain modulation
      processes, the impact of administration of alpha2-adrenoceptor agonist and
      antagonist on the density of hippocampal alpha2-adrenoceptor-immunoreactive
      neurons has not been investigated. Therefore, we aimed to determine the effect of
      single doses of clonidine and yohimbine on the density of alpha2-adrenoceptor
      immunoreactive neurons in rat hippocampus. MATERIALS AND METHODS: Adult male
      Wistar rats received a single dose of clonidine (0.7 mg/kg) alone or 5 min after
      intraperitoneal (1 mg/kg) and/or intracerebroventricular (5 ug/kg) injection of
      yohimbine. After histological processing, neurons with alpha2-adrenoceptor
      immunoreactivity were identified and counted through immunohistochemical analysis
      of hippocampal regions. RESULTS: Clonidine slightly increased the number of
      alpha2-adrenoceptor-immunoreactive neurons in the hippocampal subregions compared
      with the normal saline group. Intraperitoneal injection of yohimbine followed by
      injection of clonidine significantly increased the number of alpha2-adrenoceptor
      immunoreactive neurons in subregions cornu ammonis 1 (CA1) and cornu ammonis 3
      (CA3). Intracerebroventricular injection of yohimbine after injection of
      clonidine significantly reduced the number of alpha2-adrenoceptor-immunoreactive
      neurons in all hippocampal subregions. CONCLUSION: The present study demonstrates
      that intraperitoneal administration of alpha2-adrenoceptor agonist clonidine
      increases the density of alpha2-adrenoceptor-immunoreactive neurons in rat
      hippocampus, while intracerebroventricular injection of yohimbine decreases the
      density of these neurons.

PMID- 29064726
TI  - Relationship between wine composition and temperature: Impact on Bordeaux wine
      typicity in the context of global warming-Review.
AB  - Weather conditions throughout the year have a greater influence than other
      factors (such as soil and cultivars) on grapevine development and berry
      composition. Temperature affects gene expression and enzymatic activity of
      primary and secondary metabolism which determine grape ripening and wine
      characteristics. In the context of the climate change, temperatures will probably
      rise between 0.3 degrees C and 1.7 degrees C over the next 20 years. They are
      already rising and the physiology of grapevines is already changing. These
      modifications exert a profound shift in primary (sugar and organic acid balance)
      and secondary (phenolic and aromatic compounds) berry metabolisms and the
      resulting composition of wine. For example, some Bordeaux wines have a tendency
      toward reduced freshness and a modification of their ruby color. In this context
      it is necessary to understand the impact of higher temperatures on grape
      development, harvest procedures, and wine composition in order to preserve the
      typicity of the wines and to adapt winemaking processes.

PMID- 29064727
TI  - Proteomics for early detection of colorectal cancer: recent updates.
AB  - INTRODUCTION: Colorectal cancer (CRC) is a common type of cancer with a
      relatively poor survival rate. The survival rate of patients could be improved if
      CRC is detected early. Biomarkers associated with early stages of tumor
      development might provide useful tools for the early diagnosis of colorectal
      cancer. Areas covered: Online searches using PubMed and Google Scholar were
      performed using keywords and with a focus on recent proteomic studies. The aim of
      this review is to highlight the need for biomarkers to improve the detection rate
      of early CRC and provide an overview of proteomic technologies used for biomarker
      discovery and validation. This review will also discuss recent proteomic studies
      which focus on identifying biomarkers associated with the early stages of CRC
      development. Expert commentary: A large number of CRC biomarkers are increasingly
      being identified by proteomics using diverse approaches. However, the clinical
      relevance and introduction of these markers into clinical practice cannot be
      determined without a robust validation process. The size of validation cohorts
      remains a major limitation in many biomarker studies.

PMID- 29064729
TI  - Perceptions of experiences with interprofessional collaboration in public health
      nursing: A qualitative analysis.
AB  - In public health nursing interprofessional collaboration has become a goal,
      however, there is little clarity on the distribution of responsibility or
      approach to cooperation between the professional groups. The aim of the study was
      to explore public health nurses' perceptions of their experiences related to
      interprofessional collaboration. A qualitative content analysis was carried out.
      An interview study with a purposeful sample of 23 Norwegian public health nurses
      (PHNs) was conducted. Data were analysed using semi-structured interviews to
      identify categories and themes of PHNs' working lives. The data were classified
      into three major themes: institutionality: the institutional understanding of the
      professional roles; competence: clarifying jurisdictional borders, and
      recognition: professionals' recognition of different roles. There needs to be a
      robust strategy in collaborative working that involves public health nurses among
      other professionals to avoid role overlap, interpersonal and interprofessional
      conflict and reduce the damaging threat or stress that comes with informal or ad
      hoc rules of engagement and status claiming by one profession over another.

PMID- 29064728
TI  - Preparation and evaluation of a novel, live, attenuated influenza H1N1 vaccine
      strain produced by a modified classical reassortment method.
AB  - Live attenuated influenza vaccine (LAIV)-based Vero cells could provide a better
      choice to control and prevent influenza virus infections. This study used the
      human influenza virus A/Yunnan/1/2005Vca(H3N2) (YN/05Vca) as a donor strain.
      YN/05Vca has a double phenotype of cold adaption (ca) and Vero cell adaption
      (va). The parental virus strain used was the wild-type A/Solomon Islands/3/2006
      (H1N1) (SI/06wt). The study employed the modified classical reassortment method
      to generate a new virus strain. After co-infection of Vero cells, some different
      sub-types of the reassorted viruses were generated randomly. Then, the specific
      anti-serum (anti-YN/05Vca) could combine with and neutralize the donor virus, and
      the original parental virus could not grow in Vero cells at a low temperature
      until it was re-structured with the meaningful gene fragment from the donor virus
      in Vero cells. According to the plaques and RT-PCR results, a new monoclonal
      strain of Vero cell cold adaption virus was screened: SI/06Vca. After
      immunological and biological identification, this new strain virus could be used
      as a seed bank for LAIV, which has maintained surface antigenicity with SI/06wt.
      Consequently, this new Vero cell cold adaption virus SI/06Vca could be used for
      large-scale vaccine production with sufficient safety and efficacy, as confirmed
      by animal experiments with mice and ferrets.

PMID- 29064730
TI  - The CLOCK 3111T/C single nucleotide polymorphism and daytime fluctuations of
      gastric motility in healthy young women: A preliminary study.
AB  - The 3111T/C single nucleotide polymorphism (SNP) of Circadian Locomotor Output
      Cycles Kaput (CLOCK) gene reportedly affects gastric motility before breakfast.
      It is of interest to know whether this SNP can affect the motility during the
      daytime. We investigated the association between the CLOCK 3111T/C SNP and
      several gastric motility parameters during the time period from 8:00 to 20:00 in
      34 young women with scheduled meals. There were similar daytime fluctuations in
      gastric motility before and after the meals between the major (T/T) and minor
      (T/C) allele carriers. The CLOCK SNP may affect daytime gastric motility less
      than food stimulation.

PMID- 29064731
TI  - Suicide Lethality: A Concept Analysis.
AB  - PURPOSE: Suicide is a significant health problem internationally. Those who
      complete suicide may have different behaviors and risk factors than those who
      attempt a non-fatal suicide. The purpose of this article is to analyze the
      concept of suicide lethality and propose a clear definition of the concept
      through the identification of antecedents, attributes, and consequences. METHODS:
      A literature search for articles published in the English language between 1970
      and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit,
      Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were
      also reviewed to identify additional relevant citations. A concept analysis was
      conducted on the literature findings using six stages of Walker and Avant's
      method. FINDINGS: The concept analysis differentiated between suicide, lethality,
      suicidal behavior, and suicide lethality. Presence of a suicide plan or a written
      suicide note was not found to be associated with the majority of completed
      suicides included in the definition of suicide lethality. There are a few scales
      that measure the lethality of a suicide attempt, but none that attempt to measure
      the concept of suicide lethality as described in this analysis. CONCLUSIONS:
      Clarifying the concept of suicide lethality encourages awareness of the
      possibility of different suicidal behaviors associated with different suicide
      outcomes and will inform the development of future nursing interventions. A
      clearer definition of the concept of suicide lethality will guide clinical
      practice, research, and policy development aimed at suicide prevention.

PMID- 29064732
TI  - Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy
      Children and Patients with Mucopolysaccharidosis III: Perspective for AAV
      Mediated Gene Therapy.
AB  - Recombinant adeno-associated virus (AAV) vectors are promising gene therapy
      tools. However, pre-existing antibodies (Abs) to many useful AAV serotypes pose a
      critical challenge for the translation of gene therapies. As part of AAV gene
      therapy program for treating mucopolysaccharidosis (MPS) III patients, the
      seroprevalence profiles of AAV1-9 and rh74 were investigated in MPS IIIA/IIIB
      patients and in healthy children. Using enzyme-linked immunosorbent assay for
      alphaAAV-IgG, significantly higher seroprevalence was observed for AAV1 and
      AAVrh74 in 2- to 7-year-old MPS III patients than in healthy controls.
      Seroprevalence for the majority of tested AAV serotypes appears to peak before 8
      years of age in MPS III subjects, with the exception of increases in alphaAAV8
      and alphaAAV9 Abs in 8- to 19-year-old MPS IIIA patients. In contrast,
      significant increases in seroprevalence were observed for virtually all tested
      AAV serotypes in 8- to 15-year-old healthy children compared to 2- to 7-year
      olds. Co-prevalence and Ab level correlation results followed the previously
      established divergence-based clade positions of AAV1-9. Interestingly, the
      individuals positive for alphaAAVrh74-Abs showed the lowest co-prevalence with
      Abs for AAV1-9 (22-40%). However, all or nearly all (77-100%) of subjects who
      were seropositive for any of serotypes 1-9 were also positive for alphaAAVrh74
      IgG. Notably, the majority (78%) of alphaAAV seropositive individuals were also
      Ab-positive for one to five of the tested AAV serotypes, mostly with low levels
      of alphaAAV-Abs (1:50-100), while a minority (22%) were seropositive for six or
      more AAV serotypes, mostly with high levels of alphaAAV-IgG for multiple
      serotypes. In general, the highest IgG levels were reactive to AAV2, AAV3, and
      AAVrh74. The data illustrate the complex seroprevalence profiles of AAV1-9 and
      rh74 in MPS patients and healthy children, indicating the potential association
      of AAV seroprevalence with age and disease conditions. The broad co-prevalence of
      Abs for different AAV serotypes reinforces the challenge of pre-existing alphaAAV
      Abs for translating AAV gene therapy to clinical applications, regardless of the
      vector serotype.

PMID- 29064734
TI  - Characteristics of general movements in preterm infants assessed by computer
      based video analysis.
AB  - BACKGROUND: Previous evidence suggests that the variability of the spatial center
      of infant movements, calculated by computer-based video analysis software, can
      identify fidgety general movements (GMs) and predict cerebral palsy. AIM: To
      evaluate whether computer-based video analysis quantifies specific
      characteristics of normal fidgety movements as opposed to writhing general
      movements. METHODS: A longitudinal study design was applied. Twenty-seven low-to
      moderate-risk preterm infants (20 boys, 7 girls; mean gestational age 32 [SD 2.7,
      range 27-36] weeks, mean birth weight 1790 grams [SD 430g, range 1185-2700g])
      were videotaped at the ages of 3-5 weeks (period of writhing GMs) and 10-15 weeks
      (period of fidgety GMs) post term. GMs were classified according to Prechtl's
      general movement assessment method (GMA) and by computer-based video analysis.
      The variability of the centroid of motion (CSD), derived from differences between
      subsequent video frames, was calculated by means of computer-based video analysis
      software; group mean differences between GM periods were reported. RESULTS: The
      mean variability of the centroid of motion (CSD) determined by computer-based
      video analysis was 7.5% lower during the period of fidgety GMs than during the
      period of writhing GMs (p = 0.004). CONCLUSION: Our findings support that the
      variability of the centroid of motion reflects small and variable movements
      evenly distributed across the body, and hence shows that computer-based video
      analysis qualifies for assessment of direction and amplitude of FMs in young
      infants.

PMID- 29064735
TI  - Opioid Misuse Trends in Treatment Seeking Populations: Revised Prescription
      Opioid Policy and Temporally Corresponding Changes.
AB  - BACKGROUND: Over the last two decades, U.S. rates of prescription opioid (PO)
      misuse have risen drastically. In response, federal and state governments have
      begun to implement new PO policies. Recent legislative changes warrant up-to-date
      assessments of today's misuse rates. OBJECTIVE: To explore potential changes in
      opioid misuse trends among substance-using treatment seekers, in temporal
      relation to legislative response. METHODS: Substance-use data were collected from
      two cross-sectional Florida-based inpatient cohorts during periods preceding (pre
      policy; n = 647) and following (post-policy; n = 396) statewide PO policy
      initiatives. Participants provided information concerning their most frequently
      used drugs before treatment. PO and illicit opioid (IO) use prevalence, frequency
      and route of administration were examined for pre-policy vs. post-policy cohort
      differences. RESULTS: Relative to the pre-policy cohort, a greater percentage of
      the post-policy cohort reported recent misuse, daily use, and intravenous
      administration of POs. IO use was also more frequently reported post-policy. Non
      opioid drug use prevalence did not significantly differ between cohorts. Among
      the opioid-using subsample, equivalent percentages of the pre- and post-policy
      cohorts reported the use of POs without IOs, IOs without POs, and POs/IOs
      concurrently. Conclusions/Importance: Florida's PO policy amendments were
      temporally accompanied by a higher prevalence of PO misuse and IO use among
      treatment-seekers assessed in this study. Whether our data reflect increased
      awareness of and treatment seeking for opioid use disorders or insufficient
      efficacy of new policies to reduce opioid misuse remains in question. Regardless,
      findings suggest the need for enhanced emphasis on mitigating hazardous PO-use
      behaviors (e.g., IV use).

PMID- 29064733
TI  - A novel tool for naturalistic assessment of behavioural dysregulation after
      traumatic brain injury: A pilot study.
AB  - OBJECTIVE: This study aimed to develop a novel tool for measuring behavioural
      dysregulation in adults with traumatic brain injury (TBI) using objective data
      sources and real-world application and provide preliminary evidence for its
      psychometric properties. RESEARCH DESIGN: Fourteen adults with TBI receiving
      services at a local brain injury rehabilitation programme completed multiple
      assessments of behaviour and followed by a series of challenging problem-solving
      tasks while being video recorded. Trained clinicians completed post-hoc
      behavioural assessments using the behavioural dysregulation ratings scale, and
      behavioural event data were then extracted for comparison with self-report
      measures. RESULTS: Subject matter experts in neurorehabilitation were in 100%
      agreement that preliminarily, the new tool measured the construct of behavioural
      dysregulation. Construct validity was established through strong convergence with
      'like' measures and weak correlation with 'unlike' measures. Substantial inter
      rater reliability was established between two trained clinician raters.
      CONCLUSIONS: This study provides preliminary evidence supporting the use of a new
      precision measurement tool of behaviour in post-acute TBI that has the capability
      to be deployed naturalistically where deficits truly manifest. Future large
      scaled confirmatory psychometric trials are warranted to further establish the
      utility of this new tool in rehabilitation research.

PMID- 29064736
TI  - Safety of Staphylococcus aureus four-antigen and three-antigen vaccines in
      healthy adults: A meta-analysis of randomized controlled trials.
AB  - PURPOSE: Two new Staphylococcus aureus vaccines, S. aureus four-antigen (SA4Ag)
      and three-antigen (SA3Ag) vaccines, have good immunogenicity and tolerance.
      However, the safety of these vaccines is worth exploring. Here, we performed a
      meta-analysis to investigate the safety of SA3Ag and SA4Ag by evaluating systemic
      and local adverse events. METHODS: The Medline, EMBASE, and Cochrane databases
      were searched for randomized clinical trials confirming the safety of SA4Ag and
      SA3Ag. Two investigators independently selected suitable trials, assessed trial
      quality, and extracted data. RESULTS: Three studies comprising a total of 1,148
      participants were included in this review. The two S. aureus vaccines did not
      increase systemic adverse events (relative ratio 1.1 [95% confidence interval
      0.98, 1.24]), but increased the incidence of local adverse events (2.89 [2.15,
      3.90]). However, the incidence of severe local adverse events (4.06 [0.78,
      21.24]) did not rise significantly. CONCLUSIONS: SA4Ag and SA3Ag have acceptable
      safety in adults.

PMID- 29064737
TI  - Effects of APOE haplotypes and measures of cardiovascular risk over gender
      dependent cognitive and functional changes in one year in Alzheimer's disease.
AB  - BACKGROUND: Illiteracy, high cerebrovascular risk and copies of APOE-epsilon4 are
      risk factors for Alzheimer's disease dementia (AD). We aimed to investigate the
      impacts of gender, education, coronary heart disease (CHD) risk and creatinine
      clearance variations, body mass index (BMI) and APOE haplotypes over the rates of
      cognitive and functional decline of AD in one year. METHODS: Consecutive
      outpatients with late-onset AD were assessed for gender, schooling, BMI and APOE
      haplotypes, variations in one year of creatinine clearance and Framingham
      projections of the 10-year absolute CHD risk, and prospective scores of the Mini
      Mental State Examination (MMSE), the Clinical Dementia Rating Sum-of-Boxes (CDR
      SOB), the Index of Independence in Activities of Daily Living (ADL) and Lawton's
      Scale for Instrumental Activities of Daily Living (IADL). RESULTS: For 191
      patients, mean age at AD onset was 73.26 +/- 6.4 years-old, earlier for APOE
      epsilon4/epsilon4 carriers (p = 0.0039). For women, higher BMI led to
      improvements in CDR-SOB (beta = -0.091; p = 0.037) and MMSE (beta = 0.126; p =
      0.017) scores, while increased creatinine clearance was associated with
      improvements in ADL (beta = 0.028; p = 0.012) and MMSE (beta = 0.043; p = 0.039)
      scores and higher schooling led to faster worsening of IADL (beta = -0.195; p =
      0.022) scores. No variables impacted cognitive or functional decline for men,
      whereas copies of APOE-epsilon4 and the CHD risk had no significant effects
      whatsoever. CONCLUSIONS: Higher BMI and creatinine clearance are protective
      regarding cognitive and functional decline for women, whereas higher cognitive
      reserve may lead to faster decline in instrumental functionality. APOE haplotypes
      affected the age at AD onset, but not cognitive or functional decline.

PMID- 29064738
TI  - Effects of STING stimulation on macrophages: STING agonists polarize into
      "classically" or "alternatively" activated macrophages?
AB  - Stimulator of interferon genes (STING) was defined as an important molecule for
      promoting antitumor immunity through mediating type I interferon (IFN) production
      by sensing its ligands such as cyclic GMP-AMP (cGAMP). Our recent study indeed
      demonstrated that intratumoral injection of cGAMP showed effective antitumor
      responses via accumulating activated macrophages in the tumor microenvironment in
      a STING-dependent manner. Because the antitumor effect of cGAMP was abrogated
      when macrophages were depleted, the existence of the activated macrophages in the
      tumor site would be important for effective antitumor immune responses.
      Macrophages show phenotypic diversity and plasticity and are categorized into
      several groups by stimulation factors, e.g. IFN-gamma and IL-4 for M1 and M2
      macrophages, respectively. However, the impact of STING stimulation on the
      macrophage activation status remains to be evaluated. Here we summarize the
      complex polarized status of macrophages and the signaling cascade triggered by
      STING stimulation and also discuss the impact of STING signaling on the
      macrophage activation status for future directions.

PMID- 29064739
TI  - Estimation of the Most Influential Factors for Survival Probability Prediction of
      Prostate Cancer Patients.
AB  - The objective of the study was to address some important questions related to
      prostate cancer treatments and survivorship. One of possibility to improve the
      survival probability of prostate cancer patients is to improve predictive
      strategies. Therefore in this article was created short-term multistep ahead
      predictive model for survival probability prediction of prostate cancer patients.
      Neuro-fuzzy model was used to select the most important inputs for the predictive
      model. As the inputs, current and time lagged variables were used. The results
      could be useful for simplification of predictive models to avoid multiple inputs.

PMID- 29064741
TI  - Measurement of Wavelength and Temperature-Dependent Optical Properties of
      Thermochromic Pigments.
AB  - Thermochromic material is a substance that is capable of changing reversibly the
      color as the temperature rises. Therefore, the optical spectrum of thermochromic
      material is responsive to the environmental temperature. In this study, the
      temperature-dependent optical constants of thermochromic pigments over the
      wavelength of 350-1800 nm were investigated. Three kinds of thermochromic
      pigments featured with black, blue, and red colors at room temperature were
      suspended in water and the light reflection and transmission of the suspensions
      at different temperatures were measured by a multifunctional spectrophotometer.
      It was found that below the transition temperature of thermochromic material, the
      refractive index was 2.1-2.5, 2.2-2.6, and 2.0-2.4 over the wavelength range of
      350-1800 nm for black, blue, and red thermochromic pigment, respectively, while
      above the transition temperature it reached 2.3-2.7, 2.4-2.9, and 2.4-2.7,
      respectively. It was also observed that the relationship between refractive index
      of thermochromic pigment and wavelength follows the cubic polynomial function.
      Furthermore, the extinction coefficient is in the range of 1 * 10-5-1.2 * 10-4
      for all thermochromic pigments and remains approximately stable at different
      temperatures. The determination of optical constants of thermochromic pigments
      provides essential parameters in the modeling of light scattering and absorption
      by pigment particles to further fine-tune the optical properties of thermochromic
      coating.

PMID- 29064740
TI  - Organophosphorus flame retardants (PFRs) and phthalates in floor and road dust
      from a manual e-waste dismantling facility and adjacent communities in Thailand.
AB  - This study was undertaken to investigate levels of organophosphorus flame
      retardants (PFRs) and phthalates in floor and road dust from a manual e-waste
      dismantling facility and nearby communities in Thailand. Concentrations of
      Sigma10 PFRs and Sigma6 phthalates in floor dust from the facility were
      approximately 36-1,700 and 86,000-790,000 ng g-1, whereas those from the
      communities were about 13-9,200 and 44,000-2,700,000 ng g-1, respectively. The
      highest content of Sigma10 PFRs (9,200 ng g-1) and Sigma6 phthalates (2,700,000
      ng g-1) in indoor dust was both detected in the dust sampled from a house with no
      prevailing winds located 350 m northeast of the facility. Levels of Sigma10 PFRs
      and Sigma6 phthalates in road dust from the facility were around 1,100-2,100 and
      40,000-670,000 ng g-1, while those from the residences were about 650-2,000 and
      27,000-650,000 ng g-1, respectively. Concentrations of Sigma10 PFRs (2,100 ng g
      1) and Sigma6 phthalates (670,000 ng g-1) in road dust were greatest in the dust
      collected from the facility. For the distributional pattern, TBEP (tris (2
      butoxyethyl) phosphate) was the main PFR in residential dust, whereas TPP
      (triphenyl phosphate) was the major PFR in facility dust. TBEP was also found to
      be the most prominent PFR in all road dust samples. Furthermore, DEHP (di-2
      ethylhexyl phthalate) was the most abundant phthalate congener in both floor and
      road dust samples. Under realistic high-end scenarios of environmental exposure
      to DEHP, Thai toddlers (25.29 ug kg-1 bw day-1) in the adjacent communities were
      exposed above the US EPA's (United States Environmental Protection Agency)
      reference dose (RfD) for this congener (20 ug kg-1 bw day-1). Our data reveal
      that the PFR and phthalate-containing products at the residences are a likely
      substantial source of PFRs and phthalates to the surrounding indoor environment,
      and humans can be exposed to PFRs and phthalates in their dwellings via the
      settled floor dust.

PMID- 29064742
TI  - Seasonal effects on the sleep-wake cycle, the rest-activity rhythm and quality of
      life for Japanese and Thai older people.
AB  - BACKGROUND: The sleep-wake cycle and the rest-activity rhythm are known to change
      with aging, and such changes have been implicated in higher levels of depression
      as well as an increased incidence of dementia. However, information supporting
      seasonal changes in the sleep-wake cycle, the rest-activity rhythm and quality of
      life in older community-dwelling people remains insufficient. The aim of the
      present study was to prospectively investigate seasonal effects on the sleep-wake
      cycle, the rest-activity rhythm and quality of life among older people living in
      areas of Japan or Thailand with different climate classifications. METHOD: The
      survey was conducted from March 2016 to May 2017, and 109 participants were
      recruited from Japan and Thailand: 47 older people living in Akita prefecture,
      Japan, and 62 older people living in Chiang Mai or Nakhon Ratchasima, Thailand.
      According to the Koppen-Geiger classification of Asian climates comprising
      tropical, desert, steppe, temperate and subarctic climates, Akita prefecture,
      which is located in northern Japan, is classified as a humid subarctic climate,
      while the Thai study areas are classified as tropical savanna. To monitor
      parameters of the sleep-wake cycle during nighttime (e.g. total sleep time, sleep
      latency, sleep efficiency, awaking time and frequency of sleep interruptions) and
      to calculate parameters of the rest-activity rhythm over the 24 h profile (e.g.,
      interdaily stability, intradaily variability, relative amplitude, mean of least
      active 5 h period and mean of most active 10 h period), all the participants from
      both countries wore an Actiwatch 2 device on their nondominant wrist continuously
      for 7 days during each local season. The World Health Organization Quality of
      Life Questionnaire-BREF (WHOQOL-BREF) was also assessed during each local season.
      RESULTS: The final sample size was 37 older people living in Akita prefecture,
      Japan, and 44 older people living in Thailand; these subjects completed the data
      collections during each local season. The dropout rates were 21% in Japan and 29%
      in Thailand. The results for the Japanese subjects showed a significantly shorter
      sleep time with higher levels of activity during the nighttime on summer (p <
      0.001) and a fragmented rest-activity rhythm over the 24 h profile on winter (p <
      0.001). The older Thai participants exhibited a poor state of night sleeping year
      round, and a significant relationship was observed between seasonal variations in
      motor activity and the social domain of WHOQOL-BREF for each Thai season (|r| =
      0.4, p < 0.01). CONCLUSION: These findings provide new and important information
      regarding seasonal effects on the sleep-wake cycle, the rest-activity rhythm and
      quality of life in older community-dwelling people living in two different Asian
      climates. Consequently, clinical preventions targeting such seasonal variations
      might be useful for improving the quality of life of older Japanese and Thai
      individuals.

PMID- 29064743
TI  - Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese
      Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot
      Randomized Study.
AB  - BACKGROUND: Weight loss is often nonsustainable after liraglutide cessation. The
      present study is the first insight into the potential prevention of weight regain
      in obese subjects who have been withdrawn from liraglutide. We evaluated whether
      dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in adjunct to metformin
      prevents body weight regain more effectively than metformin alone in obese
      polycystic ovary syndrome (PCOS) previously treated with liraglutide. METHODS: A
      12-week prospective randomized open-label study was conducted with 24 obese women
      with PCOS who had been pretreated with liraglutide 3.0 mg due to antiobesity
      management (aged 34.3 +/- 6.8 years, body mass index [BMI] 36.3 +/- 5.2 kg/m2,
      mean +/- standard deviation). They were randomized to combined treatment (COMBO)
      with sitagliptin 100 mg per day (QD) and metformin (MET) 1000 mg twice daily
      (BID) (n = 12) or MET 1000 mg BID (n = 12). Lifestyle intervention was promoted
      in both groups. The primary outcome was change in anthropometric measures of
      obesity. RESULTS: Women treated with MET regain 4.7 +/- 2.7 kg (P = 0.002)
      compared with a 0.9 +/- 2.5 kg in COMBO (P = 0.147). BMI increased for 1.7 +/-
      0.9 kg/m2 in MET (P = 0.002) compared with 0.3 +/- 0.8 kg/m2 increase in COMBO (P
      = 0.136). MET group regain 4.5% +/- 2.5% of body weight as opposed to 0.8% +/-
      2.6% in COMBO. The between-treatment differences were significant for weight
      change (P < 0.001), percentage of weight change (P < 0.001), and BMI change (P <
      0.001). Greater ability to resist emotional eating was demonstrated in COMBO.
      CONCLUSION: Sitagliptin in adjunct to metformin prevented weight regain in obese
      women with PCOS previously treated with liraglutide.

PMID- 29064744
TI  - Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of
      Clinical Oncology Endorsement of the American Society for Radiation Oncology
      Evidence-Based Clinical Practice Guideline.
AB  - Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence
      based guideline on radiation therapy in oropharyngeal squamous cell carcinoma
      (OPSCC) that was determined to be relevant to the American Society of Clinical
      Oncology (ASCO) membership. After applying standard critical appraisal policy and
      endorsement procedures, ASCO chose to endorse the ASTRO guideline. Methods The
      ASTRO guideline was reviewed by ASCO content experts for clinical accuracy and by
      ASCO methodologists for developmental rigor. On favorable review, an ASCO Expert
      Panel was convened to review the guideline contents and recommendations. The ASCO
      guideline approval body, the Clinical Practice Guidelines Committee, approved the
      final endorsement. Results The ASCO Expert Panel determined that the ASTRO
      guideline recommendations, published in July 2017, are clear, thorough, and based
      upon the most relevant scientific evidence. ASCO endorsed the ASTRO guideline and
      added minor qualifying statements. Recommendations Recommendations for the
      addition of systemic therapy to definitive radiotherapy in the treatment of
      OPSCC, postoperative radiotherapy with and without systemic therapy following
      primary surgery of OPSCC, induction chemotherapy in the treatment of OPSCC, and
      the appropriate dose, fractionation, and volume regimens with and without
      systemic therapy in the treatment of OPSCC are outlined for a variety of disease
      stages and clinical scenarios. ASCO Endorsement Panel qualifying statements and
      minor modifications were made to the ASTRO recommendations. The staging system
      that is referenced in these guidelines is the American Joint Committee on Cancer
      Staging Manual, 7th edition. Additional information is available at:
      www.asco.org/head-neck-cancer-guidelines and www.asco.org/guidelineswiki .

PMID- 29064745
TI  - Timing of the interim analysis in adaptive enrichment designs.
AB  - With increasing interest in personalized medicine over the last years, study
      designs allowing to demonstrate efficacy in particular subgroups of the overall
      patient population become more important. Adaptive enrichment designs provide the
      possibility to both selecting the target population with the most promising
      treatment benefit and testing for efficacy within a single trial. Here, the
      target population is selected in a prespecified interim analysis. So far, it has
      not been very well investigated how timing of the interim analysis should be
      chosen. We investigate the impact of the interim analysis timing on power for the
      situation of a normally distributed outcome considering two different classes of
      selection rules. The interim selection is based either on the estimated effect
      difference between subgroup and total population or on absolute effect estimates.
      In this article, we demonstrate that there are indeed scenarios in which the
      timing of the interim analysis has a large impact on power. However, no
      universally applicable timing with favorable performance exist since power
      depends on treatment effects, subgroup prevalence, and especially the applied
      selection rule. Instead, the operating characteristics should be investigated for
      the specific scenario at hand to determine the most appropriate timing.

PMID- 29064746
TI  - "Kiss myAsthma": Using a participatory design approach to develop a self
      management app with young people with asthma.
AB  - OBJECTIVE: Young people with asthma often lack engagement in self-management.
      Smartphone apps offer an attractive, immediate method for obtaining asthma
      information and self-management support. In this research we developed an
      evidence-based asthma app tailored to young peoples needs, created using a
      participatory design approach to optimize user engagement. This paper describes
      the participatory design process. METHODS: This multi-phased research included
      concept generation and ideation of app design by young people with asthma, and
      development of asthma information by the research team. Clinical review was
      sought regarding safety and accuracy of app content. Participants suggestions for
      improvement and any problems with the app were logged throughout. Our young co
      designers were invited back to test a high fidelity prototype app using a "think
      aloud" process and completed a usability questionnaire. RESULTS: Twenty asthma
      patients aged 15-24 years contributed to the initial app design. Three
      respiratory specialists and two pharmacists suggested minor corrections to
      clinical terminology in the app which were all incorporated. Nine co-designers
      acted as expert reviewers of the prototype app, of whom eight completed a
      usability questionnaire. Median usability scores (maximum score 6) indicated high
      satisfaction with app content, usefulness and ease of use [median item score 5.3
      (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype
      app. CONCLUSIONS: A clinically sound asthma app has been developed which is
      considered highly acceptable to the young co-designers. A six-week test of the
      engagement, acceptability, and usefulness of the app in young people not involved
      in the participatory design will follow.

PMID- 29064747
TI  - Challenges Encountered by Nurses Working in Acute Psychiatric Wards: A
      Qualitative Study in Iran.
AB  - BACKGROUND: The provision of care to patients with psychiatric disorders and
      working in a challenging environment lead to many problems among psychiatric
      nurses. The aim of this study was to explore the challenges nurses faced while
      working in acute psychiatric wards. DESIGN: A qualitative design using content
      analysis was used. Fifteen nurses working in psychiatric wards in hospitals
      affiliated to a university hospital in an urban area of Iran were chosen using a
      purposive sampling approach. Semi-structured interviews were used for data
      collection. An inductive content analysis method was used to analyse the
      collected data. RESULTS: Four themes were developed based on the analysed data:
      "experiencing psycho-social challenges," "experiencing psychological challenges,"
      "encountering catalysts causing challenges," and "employing various strategies
      for coping with challenges." CONCLUSIONS: Given the importance of physical and
      mental well-being of nurses and the moral and professional responsibility of an
      organization to protect staff health, it is of prime importance to examine the
      inpatient psychiatric nurses' experiences to better understand them and hopefully
      use such knowledge so as to improve their work life.

PMID- 29064748
TI  - The Future of Contrast-Enhanced Mammography.
AB  - OBJECTIVE: The purpose of this article is to discuss facilitators of and barriers
      to future implementation of contrast-enhanced mammography (CEM) in the United
      States. CONCLUSION: CEM provides low-energy 2D mammographic images analogous to
      digital mammography and contrast-enhanced recombined images that allow assessment
      of neovascularity similar to that offered by MRI. The utilization of CEM in the
      United States is currently low but could increase rapidly given the many
      potential indications for its clinical use.

PMID- 29064749
TI  - Variability of Postsurgical Imaging Surveillance of Breast Cancer Patients: A
      Nationwide Survey Study.
AB  - OBJECTIVE: Because of observed clinical variance and the discretion of referring
      physicians and radiologists in patient follow-up, the purpose of this study was
      to conduct a survey to explore whether broad discrepancy exists in imaging
      protocols used for postsurgical surveillance. SUBJECTS AND METHODS: An online
      survey was created to assess radiologists' use of diagnostic versus screening
      mammography for women with a personal history of breast cancer and determine
      whether the choice of protocol was associated with practice characteristics
      (setting, region, and reader type). RESULTS: Of 8170 surveys sent, 849 (10%)
      completed responses were returned. Seventy-nine percent of respondents
      recommended initial diagnostic mammography after lumpectomy (65% at 6 months, 14%
      at 12 months); 49% recommended diagnostic surveillance for up to 2 years before a
      return to screening mammography; and 33% continued diagnostic surveillance for 2
      5 years before returning to screening. For imaging after mastectomy, 57% of
      respondents recommended diagnostic mammography of the unaffected breast. Among
      the 57%, however, 37% recommended diagnostic screening for only the first
      postmastectomy follow-up evaluation, and the other 20% permanently designated
      patients for diagnostic mammography after mastectomy. CONCLUSION: The optimal
      surveillance mammography regimen must be better defined. This preliminary study
      showed variability in diagnostic versus screening surveillance mammography for
      women with a history of breast cancer. Future studies should evaluate why these
      variations occur and how to standardize recommendations to tailor personalized
      imaging.

PMID- 29064750
TI  - The Attenuation Distribution Across the Long Axis of Breast Cancer Liver
      Metastases at CT: A Quantitative Biomarker for Predicting Overall Survival.
AB  - OBJECTIVE: The objective of our study was to compare attenuation distribution
      across the long-axis (ADLA) measurements, Response Evaluation Criteria in Solid
      Tumors (RECIST) version 1.1, and Choi criteria for predicting overall survival
      (OS) in patients with metastatic breast cancer treated with bevacizumab.
      MATERIALS AND METHODS: We obtained HIPAA-compliant data from a prospective,
      multisite, phase 3 trial of bevacizumab for the treatment of metastatic breast
      cancer. For patients with one or more liver metastases measuring 15 mm or larger
      at baseline, we evaluated up to two target liver lesions using RECIST, Choi
      criteria, and ADLA measurements, with the latter defined as the SD of the CT
      attenuation values of each pixel along the tumor long-axis diameter. The optimal
      percentage change threshold for defining an ADLA response was computed by cross
      validation analysis in a Cox model. The log-rank test was applied to evaluate
      RECIST, Choi criteria, and ADLA for discriminating patients with superior OS. The
      predictive accuracies of all three techniques were compared using Brier scores
      and areas under the ROC curve (AUC). All analyses were performed separately using
      best overall response (BOR) and response at the first follow-up time point (FU1).
      RESULTS: One hundred sixty-four patients met the inclusion criteria. A 25%
      decrease in the ADLA measurement from baseline was the optimal ADLA response
      threshold for BOR and FU1. RECIST, Choi criteria, and ADLA successfully
      identified patients with superior OS when using BOR (RECIST, p = 0.02; Choi and
      ADLA, p < 0.001), but only Choi criteria and ADLA measurements were successful
      when using FU1 (RECIST, p = 0.43; Choi and ADLA, p < 0.001). In a direct
      comparison, ADLA measurements outperformed both RECIST and Choi criteria using
      BOR (95% CI for Brier score differences, ADLA-RECIST [-0.58 to -0.08] and ADLA
      Choi [-0.55 to -0.06]; 95% CI for AUC differences, ADLA-RECIST [0.16-0.33] and
      ADLA-Choi [0.17-0.36]) as well as using FU1 (95% CI for Brier score differences,
      ADLA-RECIST [-0.77 to -0.08] and ADLA-Choi [-0.58 to -0.03]; 95% CI for AUC
      differences, ADLA-RECIST [0.22-0.39] and ADLA-Choi [0.01-0.22]). CONCLUSION: ADLA
      measurements may be a useful noninvasive indicator of cancer treatment response.
      Because ADLA measurements may be extracted relatively easily using existing
      radiologist workflows, further investigation of the ADLA technique is warranted.

PMID- 29064752
TI  - Improving Clinical Information on Head CT Requisitions From the Emergency
      Department to Aid Interpretation and Billing Efficiency.
AB  - OBJECTIVE: The accuracy of radiologic interpretations is higher when appropriate
      clinical information is provided, as is the likelihood of reimbursement for the
      studies. The purpose of this project was to evaluate and improve the quality of
      clinical information provided on head CT requisitions from an urban emergency
      department (ED). SUBJECTS AND METHODS: In a prospective study conducted from July
      2015 to May 2016, attending neuroradiologists evaluated 1100 randomly selected ED
      requisitions for unenhanced head CT, grading them for clinical and billing
      adequacy on a scale of 0-2. After acquisition of baseline data (400 studies), an
      intervention was performed that consisted of education of ED staff on the
      importance of clinical information in requisitions. A reminder slide was placed
      on a large screen in the ED staff working area with examples of appropriate
      history. Postintervention data (700 studies) were subsequently obtained. Mean
      scores and payment lag time before versus after the intervention were compared by
      Wilcoxon rank sum test. RESULTS: Statistically significant improvement was found
      in mean scores after the intervention for both clinical (1.32 to 1.43, p = 0.003)
      and billing (1.64 to 1.74, p = 0.02) adequacy categories. The percentage of
      studies with a score of 2 increased in both categories, and the percentages of 0
      and 1 scores declined. There was a 21.1-day decrease in payment lag time (from
      75.8 to 54.7 days, p < 0.0001). CONCLUSION: The quality of clinical information
      provided on imaging requisitions by ED faculty and residents improved after a
      fairly simple intervention. Billing efficiency improved, and payment lag time
      decreased substantially.

PMID- 29064751
TI  - Alternative Response Criteria and Clinical Risk Factors for Assessing Tumor
      Response in Patients With Metastatic Renal Cell Carcinoma Who Are Receiving
      Salvage Therapy.
AB  - OBJECTIVE: The purpose of this study is to compare the prognostic value of
      various solid tumor response criteria as well as the additive value of clinical
      risk factors in patients with advanced renal cell carcinoma (RCC). MATERIALS AND
      METHODS: Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months
      after treatment) were reviewed for 57 patients with metastatic RCC treated with
      pazopanib in the salvage setting. Tumor response on the posttherapy scan was
      evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi,
      modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and
      10% threshold criteria. In addition, combined Memorial Sloan-Kettering Cancer
      Center (MSKCC) risk factors plus imaging criteria were used to define response
      groups. Response evaluations using these criteria were correlated with overall
      survival (OS) and progression-free survival (PFS), with use of the log-rank test.
      RESULTS: Patients classified as having progressive disease (PD) on the basis of
      RECIST, mChoi, and MASS criteria had a significantly worse OS than patients with
      stable disease (SD) and partial response (PR). With the addition of MSKCC risk
      factors, all groups with PD defined by combined criteria had significantly worse
      OS. For 37 patients with no or one MSKCC risk factor, response groups defined by
      Choi, mChoi, MASS, and 10% threshold criteria did not differ in PFS or OS.
      However, among 20 patients with two to three MSKCC risk factors, those classified
      as having PR had longer PFS than did those with SD and had longer OS than did
      those with PD. CONCLUSION: For patients with advanced RCC for which prior
      therapies have failed, the prognostic value of various imaging-based tumor
      response criteria differs on the basis of the MSKCC clinical risk status.

PMID- 29064753
TI  - Ultrasound Features of Mammographic Developing Asymmetries and Correlation With
      Histopathologic Findings.
AB  - OBJECTIVE: The purpose of this study is to review the ultrasound (US) features of
      developing asymmetries and correlate them with histopathologic findings.
      MATERIALS AND METHODS: We searched the mammography database of an academic
      medical center, affiliated cancer center, and two ambulatory imaging facilities
      from 2009 to 2012 and identified 201 patients with developing asymmetries, 187 of
      whom had US at the time of, or within 1 month of, diagnostic mammography
      evaluation. Seventy-five (40.1%) of these 187 patients had a US correlate, and
      three additional patients had a positive second-look US after MRI (US results
      were initially negative), and one patient had a US correlate for a newly palpable
      developing asymmetry 1 month after receiving a BI-RADS category 3 mammography
      only assessment. These 78 developing asymmetries with US correlates comprised the
      study cases. US features were obtained by consensus image review; patient
      demographic characteristics and outcomes were obtained from the electronic
      medical record. RESULTS: Thirty-six of 78 US correlates (46.2%) were masses, the
      echotexture of which was as follows: 26 (72.2%) were hypoechoic, four (11.1%)
      were hyperechoic, three (8.3%) were mixed hyperechoic and hypoechoic, and three
      (8.3%) were anechoic. Forty-two of 78 US correlates (53.8%) were nonmass
      findings, the echotexture of which was as follows: 24 (57.1%) were mixed
      hyperechoic and hypoechoic, 13 (31.0%) were hypoechoic, and five (11.9%) were
      hyperechoic. Twenty-one of 78 lesions (26.9%) were malignant; of these, eight
      were invasive ductal carcinoma, seven were invasive lobular carcinoma, three were
      mixed invasive ductal and lobular carcinoma, and three were ductal carcinoma in
      situ. Malignant findings on US included 17 masses (81.0%) (13 hypoechoic and four
      mixed hyperechoic and hypoechoic), and four nonmass findings (19.0%) (three mixed
      hyperechoic and hypoechoic and one hypoechoic). CONCLUSION: When present, US
      correlates for developing asymmetries are often nonmass findings with mixed
      echotexture. Most malignant developing asymmetries with US correlates present as
      a hypoechoic mass, but 19% present as a nonmass finding with either mixed
      hyperechoic and hypoechoic echotexture or hypoechoic echotexture.

PMID- 29064755
TI  - Fat-Containing Liver Lesions on Imaging: Detection and Differential Diagnosis.
AB  - OBJECTIVE: The purpose of this article is to review how fat is detected on
      imaging and to discuss the differential diagnosis of fat-containing liver
      lesions. CONCLUSION: Fat is a highly useful feature in characterizing liver
      lesions on imaging. Although a variety of liver lesions can show fat on cross
      sectional imaging, the presence of fat usually indicates that the lesion is of
      hepatocellular origin. Less commonly, nonhepatocellular fatty lesions may be
      distinguished by ancillary clinical and imaging features.

PMID- 29064754
TI  - Age to Begin and Intervals for Breast Cancer Screening: Balancing Benefits and
      Harms.
AB  - OBJECTIVE: Screening mammography has been widely used for breast cancer detection
      and has been found to decrease mortality, but debate continues. The purpose of
      this article is to review screening recommendations and the benefits and
      perceived harms of earlier and more frequent screening. CONCLUSION: Annual
      mammography beginning at age 40 decreases mortality. Clinicians should educate
      women and preserve recommendations for early and annual screening.

PMID- 29064756
TI  - Concurrent Computer-Aided Detection Improves Reading Time of Digital Breast
      Tomosynthesis and Maintains Interpretation Performance in a Multireader Multicase
      Study.
AB  - OBJECTIVE: Digital breast tomosynthesis (DBT) is more accurate than full-field
      digital mammography alone but requires a longer reading time. A radiologist
      reader study evaluated the use of concurrent computer-aided detection (CAD) to
      shorten the reading time while maintaining interpretation performance. MATERIALS
      AND METHODS: A CAD system was developed to detect suspicious soft-tissue
      densities in DBT planes. Abnormalities are extracted from the plane in which they
      are detected and blended into the corresponding synthetic image. The study used
      an enriched sample of 240 DBT cases with 68 malignancies in 61 patients. Twenty
      radiologists retrospectively reviewed all 240 cases in a multireader multicase
      crossover design to compare reading time and performance with and without CAD.
      The performance of CAD alone was also evaluated. RESULTS: Reading time improved
      by 29.2% with CAD (95% CI, 21.1-36.5%; p < 0.01). Reader performance, measured by
      ROC AUC, was noninferior with CAD (p < 0.01). The mean AUC increased from 0.841
      without to 0.850 with CAD (95% CI, -0.012 to 0.030). Mean sensitivity increased
      from 0.847 without to 0.871 with CAD (difference 95% CI, -0.005 to 0.055),
      showing a 0.033 increase in sensitivity for cases with soft-tissue densities (95%
      CI, -0.002 to 0.068). Mean specificity decreased from 0.527 without to 0.509 with
      CAD (difference 95% CI, -0.041 to 0.005), and mean recall rate for noncancers
      slightly increased from 0.474 without to 0.492 with CAD (difference 95% CI, 
      0.006 to 0.041). CONCLUSION: Concurrent use of CAD with DBT resulted in 29.2%
      faster reading time, while maintaining reader interpretation performance.

PMID- 29064757
TI  - Incidental Pulmonary Embolism After Coronary Artery Bypass Surgery: Long-Term
      Clinical Follow-Up.
AB  - OBJECTIVE: The purpose of this study was to investigate the incidence and natural
      history of incidentally found and untreated pulmonary embolism (PE) at coronary
      CT angiography after coronary artery bypass grafting. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 353 patients consecutively registered
      between January 1, 2010, and November 11, 2015, who underwent coronary artery
      bypass grafting followed within 2 weeks by coronary CT angiography. All patients
      received 100 mg of aspirin and 75 mg of clopidogrel after surgery. We collected
      relevant clinical and CT data, including total follow-up duration after coronary
      artery bypass grafting, follow-up CT findings, mortality, and incidence of any
      recurrent PE. RESULTS: PE was diagnosed in 22 of the 353 patients (6.2%) who
      remained in the study after the exclusion criteria were applied. Most of the PEs
      occurred at the segmental or subsegmental level. All patients were in
      hemodynamically stable condition, had no symptoms, and underwent follow-up for a
      median of 53 months (range 19-74 months). Twenty of the 22 patients did not
      receive anticoagulation, and all but one of these patients had complete
      resolution of PE at second follow-up coronary CT angiography (median, 149 days
      after surgery). There was no associated mortality or recurrent PE. CONCLUSION:
      Incidental PE after coronary artery bypass grafting is found in approximately 6%
      of patients undergoing postoperative coronary CT angiography, and most PEs
      resolve spontaneously without anticoagulation. No patient in this study died or
      had recurrent PE during a median follow-up period of 53 months.

PMID- 29064759
TI  - Bibliometric Analysis of Manuscript Characteristics That Influence Citations: A
      Comparison of Six Major Radiology Journals.
AB  - OBJECTIVE: The objective of our study was to investigate radiology manuscript
      characteristics that influence citation rate, capturing features of manuscript
      construction that are discrete from study design. MATERIALS AND METHODS:
      Consecutive articles published from January 2004 to June 2004 were collected from
      the six major radiology journals with the highest impact factors: Radiology
      (impact factor, 5.076), Investigative Radiology (2.320), American Journal of
      Neuroradiology (AJNR) (2.384), RadioGraphics (2.494), European Radiology (2.364),
      and American Journal of Roentgenology (2.406). The citation count for these
      articles was retrieved from the Web of Science, and 29 article characteristics
      were tabulated manually. A point-biserial correlation, Spearman rank-order
      correlation, and multiple regression model were performed to predict citation
      number from the collected variables. RESULTS: A total of 703 articles-211
      published in Radiology, 48 in Investigative Radiology, 106 in AJNR, 52 in
      RadioGraphics, 129 in European Radiology, and 157 in AJR-were evaluated.
      Punctuation was included in the title in 55% of the articles and had the highest
      statistically significant positive correlation to citation rate (point-biserial
      correlation coefficient [rpb] = 0.85, p < 0.05). Open access status provided a
      low-magnitude, but significant, correlation to citation rate (rpb = 0.140, p <
      0.001). The following variables created a significant multiple regression model
      to predict citation count (p < 0.005, R2 = 0.186): study findings in the title,
      abstract word count, abstract character count, total number of words, country of
      origin, and all authors in the field of radiology. CONCLUSION: Using bibliometric
      knowledge, authors can craft a title, abstract, and text that may enhance
      visibility and citation count over what they would otherwise experience.

PMID- 29064758
TI  - A Comparison of Radiologists' and Urologists' Opinions Regarding Prostate MRI
      Reporting: Results From a Survey of Specialty Societies.
AB  - OBJECTIVE: The purpose of this study is to compare radiologists' and urologists'
      opinions regarding prostate MRI reporting. SUBJECTS AND METHODS: Radiologist
      members of the Society of Abdominal Radiology and urologist members of the
      Society of Urologic Oncology received an electronic survey regarding prostate MRI
      reporting. RESULTS: The response rate was 12% (135/1155) for Society of Abdominal
      Radiology and 8% (54/663) for Society of Urologic Oncology members. Most
      respondents in both specialties prefer Prostate Imaging Reporting and Data System
      version 2 (PI-RADSv2) (radiologists, 84%; urologists, 84%), indicate that it is
      used at their institution (radiologists, 84%; urologists, 78%), understand its
      implications for patient care (radiologists, 89%; urologists, 71%), and agree
      that radiologists apply PI-RADSv2 categories correctly (radiologists, 57%;
      urologists, 61%). Both specialties agreed regarding major barriers to PI-RADSv2
      adoption: radiologist inexperience using PI-RADSv2 (radiologists, 51%;
      urologists, 51%), urologist inexperience using PI-RADSv2 (radiologists, 46%;
      urologists, 51%), and lack of standardized templates (radiologists, 47%;
      urologists, 52%). The specialties disagreed (p <= 0.039) regarding whether
      reports should include the following management recommendations: targeted biopsy
      (radiologists, 58%; urologists, 34%), follow-up imaging (radiologists, 46%;
      urologists, 28%), and time interval for follow-up imaging (radiologists, 35%;
      urologists, 16%). There was also disagreement (p = 0.037) regarding report style:
      54% of urologists preferred fully structured reports, whereas 53% of radiologists
      preferred hybrid structured and free-text reports. CONCLUSION: Radiologists and
      urologists both strongly prefer PI-RADSv2 for prostate MRI reporting, despite
      recognizing barriers to its adoption. Urologists more strongly preferred a fully
      structured report and disagreed with radiologists' preference to include
      management recommendations. Collaborative radiologist-urologist educational
      efforts are warranted to help optimize the effect of prostate MRI reporting in
      patient care.

PMID- 29064761
TI  - Comparing the Healing Potential of Late-Stage Periodontitis and Peri-Implantitis.
AB  - Peri-implantitis is defined as an inflammatory disease affecting the tissues
      around osseointegrated functioning implants. Unfortunately, detailed peri
      implantitis pathogenesis is not well understood and current treatments lack
      predictability. Compare the healing potential of late-stage ligature-induced
      periodontitis and peri-implantitis after ligature removal. Four-week-old C57BL/6J
      male mice had their left maxillary molars extracted. After 8 weeks, implants were
      placed in healed sockets and allowed to osseointegrate. Mice were separated into
      control (no ligature) and experimental (ligature) groups. In the experimental
      group, ligatures were placed around the implant and the contralateral second
      molar. Four weeks later, the ligature group was randomly divided into ligature
      retained and ligature-removed groups. Mice were sacrificed at 2 time points: 1
      and 2 weeks after ligature removal. The samples were analyzed by microcomputed
      tomography (micro-CT) and histology. Ligature-induced significant bone loss in
      peri-implantitis and periodontitis were compared with respective controls. At the
      2-week time point, bone formation was observed in the ligature-removed groups
      compared with respective controls; however, more bone was regained in
      periodontitis ligature-removed compared with the peri-implantitis ligature
      removed group. Histologically, the peri-implantitis ligature-retained group had
      higher inflammatory levels and a higher number of osteoclasts compared with the
      periodontitis ligature-retained group. Moreover, in the peri-implantitis ligature
      retained group, collagen appeared less organized compared with the periodontitis
      ligature-retained group at both time points; although collagen tended to
      reorganize following ligature removal in both conditions. Peri-implantitis does
      not respond to treatment as well as periodontitis. Future work includes
      understanding peri-implantitis pathogenesis and developing predictable treatment
      protocols.

PMID- 29064760
TI  - Screening Mammography in Women 40-49 Years Old: Current Evidence.
AB  - OBJECTIVE: Breast cancer is an important health problem for women 40-49 years
      old, yet screening mammography for this age group remains controversial. This
      article reviews recent guidelines and supporting evidence on screening
      mammography in women of this age group. CONCLUSION: Evidence supports the benefit
      of annual screening mammography in women 40-49 years old. Models of different
      breast cancer screening strategies consistently show the greatest breast cancer
      mortality reduction and life-years gained with annual screening starting when
      women reach 40 years old.

PMID- 29064763
TI  - A Quantitative Examination of Identity Integration in Gay, Lesbian, and Bisexual
      People of Faith.
AB  - Much of the religious/spiritual development of gays, lesbians, and bisexuals
      (GLBs) has focused on experiences of conflict and distress, providing little
      insight into how these identities can be integrated. The present study explored
      the religious and spiritual lives of GLBs with a specific focus on the
      integration of these identities. We conducted a retrospective secondary data
      analysis of 750 GLB individuals from the Northern California Health Study to
      quantitatively assess sexual orientation and religion/spirituality integration
      using hierarchical cluster analysis. Resulting MANCOVA analyses of the five
      revealed groupings (integrated, gay identity struggle, anti-religious/spiritual,
      secular, and low gay salience) present numerous statistically significant
      differences between these integration clusters and a variety of dependent
      variables including measures of demographics, religiosity/spirituality, gay
      identity, and multiple mental health outcomes. We discuss the implications of
      these findings while also making suggestions for future research.

PMID- 29064762
TI  - Evaluation of the Anastomosis Canal in Lateral Maxillary Sinus Wall With Cone
      Beam Computerized Tomography: A Clinical Study.
AB  - This clinical study used cone beam computerized tomography (CBCT) to locate the
      position of the anastomosis canal in lateral wall of maxillary sinuses, and to
      evaluate the thickness of lateral sinus wall and the distance from the lower
      border of the canal to the sinus floor, which could provide surgeon with
      information about this anastomosis. Two hundred and forty-two (242) volumes of
      CBCT scans were included in this study. The distances from the lower border of
      the anastomosis canal to the sinus floor and from the maxillary alveolar crest to
      the sinus floor were evaluated in transversal plane, and the thickness of the
      lateral sinus wall was measured at the distance of 3, 6, 9 mm from the sinus
      floor and at the level of the lower border of the canal at the same plane. The
      canal was identified in 87.6% (424/484) of the sinus. Most canals were
      intraosseous, or beneath the sinus membrane. The mean distance was 9.2 +/- 3.5 mm
      from the lower border of the canal to the sinus floor, and 10.8 +/- 4.0 mm from
      the alveolar crest to the sinus floor. The thickness of the lateral sinus wall
      was 2.4 +/- 0.9 mm, 1.8 +/- 0.8 mm, 1.7 +/- 0.7 mm, 1.8 +/- 0.8 mm at the
      distance of 3, 6, 9 mm from the sinus floor and at the level of the lower border
      of the canal. The location of the anastomosis canals varied from each patient,
      but the distance from the sinus floor was similar in different teeth sites. The
      sinus floor could be an anatomic landmark of sinus floor augmentation. In order
      not to interrupt this canal, great care must be taken by the implant surgeon to
      identify this canal.

PMID- 29064765
TI  - Examination of Local Periosteal Microcirculation After Application of Absorbable
      and Nonabsorbable Membranes.
AB  - The use of different membranes is common in dentoalveolar surgery. Absorbable and
      nonabsorbable membranes are used, often beneath the periosteum, to fulfil
      different functions (as barriers, patches, or spacers). It is still unclear to
      what extent such membranes affect the biology of the periosteum and what role is
      played by piezoelectric devices during preparation of the periosteum. We placed
      two different membranes (absorbable and nonabsorbable) underneath the periosteum
      of rat calvaria. We prepared the periosteum using different methods
      (piezoelectric device vs mechanical device). We then examined and analyzed
      periosteal microcirculation over a period of 28 days. A clear difference was
      observed between the two methods when used with absorbable membranes: The
      piezoelectric device offered advantages. Absorbable membranes maintain
      considerably more local periosteal microcirculation and should be given
      preference. In addition, we observed an advantage to using a piezoelectric device
      for periosteal dissection. Therefore, this method should also be used more
      widely.

PMID- 29064764
TI  - Evaluation of Oral Stereognosis in Relation to Tactile Ability and Patient
      Satisfaction.
AB  - We investigated the oral stereognostic ability (OSA) of dentate individuals,
      conventional complete denture patients, and maxillary implant-supported denture
      patients with bar attachments. Stereognosis tests were carried out, and the
      relationship between OSA and patient satisfaction was assessed with a
      satisfaction survey: the Turkish version of the oral health impact profile-14
      (OHIP-TR-14). To compare differences in oral sensory function among individuals
      with natural dentition, complete denture wearers, and maxillary implant-supported
      denture wearers, tactile awareness (thickness perception threshold) and pressure
      awareness (threshold of lateral loading) were assessed. According to the results,
      the oral perception level of natural dentate patients was higher than that of the
      complete denture group and maxillary implant-supported complete denture group at
      the end of the study. There was no statistically significant difference in OHIP
      TR-14 scores between the maxillary implant-supported complete denture group and
      the complete denture group ( P < .05). The control group perceived the applied
      lateral and vertical forces statistically earlier than the other groups ( P <
      .001). There was no statistically significant difference between the complete
      denture and maxillary implant-supported denture groups in terms of the lateral
      pressure threshold or thickness tactile threshold ( P > .05). At the end of the
      study it was concluded that there was no correlation between oral perception
      levels and satisfaction in patients with complete dentures and patients with
      maxillary implant-supported complete dentures. The control group, compared with
      the complete denture and maxillary implant-supported complete denture groups,
      perceived the lateral and vertical forces statistically earlier than the other
      groups.

PMID- 29064766
TI  - Advanced patient transfer assist device with intuitive interaction control.
AB  - This research aims to improve patient transfers by developing a new type of
      advanced robotic assist device. It has multiple actuated degrees of freedom and a
      powered steerable base to maximize maneuverability around obstacles. An intuitive
      interface and control strategy allows the caregiver to simply push on the machine
      in the direction of desired patient motion. The control integrates measurements
      of both force and proximity to mitigate any potential large collision forces and
      provides operators information about obstacles with a form of haptic feedback.
      Electro-hydraulic pump controlled actuation provides high force density for the
      actuation. Nineteen participants performed tests to compare transfer operations
      (transferring a 250-lb mannequin between a wheelchair, chair, bed, and floor) and
      interaction control of a prototype device with a commercially available patient
      lift. The testing included a time study of the transfer operations and subjective
      rating of device performance. The results show that operators perform transfer
      tasks significantly faster and rate performance higher using the prototype
      patient transfer assist device than with a current market patient lift. With
      further development, features of the new patient lift can help facilitate patient
      transfers that are safer, easier, and more efficient for caregivers.

PMID- 29064768
TI  - Can PEEK Be an Implant Material? Evaluation of Surface Topography and Wettability
      of Filled Versus Unfilled PEEK With Different Surface Roughness.
AB  - Polyetheretherketone (PEEK) composites are biocompatible materials that may
      overcome the esthetic and allergic problems of titanium dental implants. However,
      their potential for osseointegration with a subsequent survival rate is still
      questionable. The aim of this study was to evaluate the surface roughness and
      wettability of different surface-treated filled and unfilled PEEK specimens,
      which may be indicative of the osseointegration behavior and potential use of
      PEEK as an implant material. Unfilled, ceramic-filled (CFP) and carbon fiber
      reinforced (CFRP) PEEK discs were prepared and left untreated or were surface
      treated with 50 MU, 110 MU, or 250 MU aluminum oxide particles. The roughness
      average (Ra) value of each disc was evaluated using a contact stylus
      profilometer. Their contact angles were measured to evaluate their wettability,
      which was compared among PEEK discs using ANOVA, followed by Bonferroni test for
      pairwise comparisons ( P <= .05). Regarding the surface roughness, a significant
      difference was found between unfilled and filled PEEK when untreated and
      bombarded with 50 or 110 microns of aluminum oxide particles. For the contact
      angle, a significant difference was found only among the untreated PEEK
      materials. Among the evaluated PEEK materials, CFRP50, CFRP110 and CFP110 showed
      the most favorable Ra values with good wettability properties, thus being
      potential substrates for dental implants.

PMID- 29064767
TI  - Healing at the Interface Between Autologous Block Bone Grafts and Recipient Sites
      Using n-Butyl-2-Cyanoacrylate Adhesive as Fixation: Histomorphometric Study in
      Rabbits.
AB  - The aim of the present split-mouth (split-plot) study was to describe the
      sequential healing in the interface between autologous bone grafts and recipient
      parent bone, fixed using an n-butyl-2-cyanoacrylate adhesive with or without an
      additional titanium fixation screw. Bone grafts were collected from the calvaria
      and fixed to the lateral aspect of the mandible in 24 rabbits. The cortical
      layers of the recipient sites were perforated, and the grafts were randomly fixed
      using an n-butyl-2-cyanocrylate adhesive, either alone or in conjunction with a
      1.5 mm * 6.0 mm titanium fixation screw. The animals were sacrificed after 3, 7,
      20, and 40 days, and histomorphometric evaluations of the interface between graft
      and parent bone were performed. Only 2 of 6 grafts in each group were partially
      incorporated to the parent bone after 40 days of healing. The remaining grafts
      were separated from the parent bone by adhesive and connective tissue. It was
      concluded that the use of n-butyl-2-cyanoacrylate as fixation of an autologous
      bone graft to the lateral aspect of the mandible was able to maintain the
      fixation over time but did not incorporate the graft to the recipient sites. Use
      of fixation screws did not improve the healing.

PMID- 29064770
TI  - Managing Titanium Mesh Exposure With Partial Removal of the Exposed Site: A Case
      Series Study.

PMID- 29064769
TI  - Gender differences in abdominal aortic aneurysms in Germany using health
      insurance claims data.
AB  - BACKGROUND: Endovascular aortic repair (EVAR) has emerged as standard of care for
      abdominal aortic aneurysm (AAA). Real-world evidence is limited to compare this
      technology to open repair (OAR). Major gaps exist related to short-term and long
      term outcomes, particularly in respect of gender differences. MATERIALS AND
      METHODS: Health insurance claims data from Germany's third largest insurance
      provider, DAK-Gesundheit, was used to investigate invasive in-hospital treatment
      of intact (iAAA) and ruptured AAA (rAAA). Patients operated between October 2008
      and April 2015 were included in the study. RESULTS: A total of 5,509 patients
      (4,966 iAAA and 543 rAAA) underwent EVAR or OAR with a median follow-up of 2.44
      years. Baseline demographics, comorbidities, and clinical characteristics of DAK
      G patients were assessed. In total, 84.6 % of the iAAA and 79.9 % of the rAAA
      were male. Concerning iAAA repair, the median age (74 vs. 73 years, p < .001)
      compared to men was higher in females, but their EVAR-rate (66.8 % vs. 71.1 %, p
      = .018) was lower. Besides higher age of female patients (80 vs. 75 years, p <
      .001), no further statistically significant differences were seen following rAAA
      repair. In-hospital mortality was slightly lower in males compared to females
      following iAAA (2.3 % vs. 3.1 %, p = .159) and rAAA (37.3 % vs. 43.1 %, p = .273)
      repair. Concerning iAAA repair, a higher rate of female patients was transferred
      to another hospital (3.7 % vs. 2.0 %, p = 0.008) or discharged to rehabilitation
      (6.0 % vs. 2.7 %, p < .001) compared to male patients. CONCLUSIONS: In this large
      German claims data cohort, women are generally older and more often transferred
      to another hospital or discharged to rehab following iAAA repair. Nonetheless, no
      significantly increased risk of in-hospital or late death appeared for women in
      multivariate analyses. Further studies are necessary to evaluate the impact of
      recent gender-specific treatment strategies on overall outcome under real-world
      settings.

PMID- 29064771
TI  - Contralateral prophylactic mastectomy: A qualitative approach to exploring the
      decision making process.
AB  - The proportion of women with unilateral breast cancer and no familial or genetic
      risk factors who elect contralateral prophylactic mastectomy (CPM) has grown
      dramatically, even in the absence of clear data demonstrating improved outcomes.
      To further extend the literature that addresses treatment decision-making,
      qualitative interviews were conducted with eleven women who considered CPM. A
      social ecological model of breast cancer treatment decision-making provided the
      conceptual framework, and grounded theory was used to identify the cognitive,
      psychosocial, and emotional influences motivating treatment choice. This research
      identified five themes that give context to women's decision-making experience:
      (1) variability in physician communication, (2) immediacy of the decision, (3)
      meaning of being proactive about treatment, (4) meaning of risk, and (5) women's
      relationship with their breasts. The results suggest that greater emphasis should
      be placed on a more nuanced understanding of patients' emotional reaction to
      breast cancer and managing the decision-making environment.

PMID- 29064772
TI  - Reducing diabetes distress and improving self-management with mindfulness.
AB  - Stress associated with diabetes makes managing diabetes harder. We investigated
      whether mindfulness-based stress reduction (MBSR) could reduce diabetes distress
      and improve management. We recruited 38 participants to complete an MBSR program.
      Surveys and lab values were completed at baseline and post-intervention.
      Participants showed significant improvement in diabetes-related distress (Cohen's
      d -.71, p < .002), psychosocial self-efficacy (Cohen's d .80, p < .001), and
      glucose control (Cohen's d -.79, p < .001). Significant improvements in
      depression, anxiety, stress, coping, self-compassion, and social support were
      also found. These results suggest that MBSR may offer an effective method for
      helping people better self-manage their diabetes and improve mental health.

PMID- 29064774
TI  - Using IMPrESS to guide policy change in multiple sclerosis.
AB  - The International MultiPlE Sclerosis Study (IMPrESS) studied the significant
      impact of multiple sclerosis (MS) on the health and well-being of both people
      with the disease and their caregivers, along with its broader socioeconomic
      impact. Results confirmed that there is an urgent need to achieve better outcomes
      for people with MS. This paper uses results from the IMPrESS to present new
      international evidence on the socioeconomic burden of MS and discuss the merits
      of a likely paradigm shift in the management of MS towards the use of better (and
      more accurate) diagnostic follow-up to monitor disease progression and the
      earlier use of disease-modifying treatments (DMTs) to achieve better clinical,
      quality-of-life and socioeconomic results for individuals.

PMID- 29064773
TI  - Can a Unified Service Delivery Philosophy Be Identified in Aging and Disability
      Organizations? Exploring Competing Service Delivery Models Through the Voices of
      the Workforce in These Organizations.
AB  - Services for older adults and younger people with disabilities are increasingly
      merging, as reflected in the creation of Aging and Disability Resource Centers
      (ADRCs). Using ADRCs to coordinate services is challenging, primarily because
      these fields have different service delivery philosophies. Independent Living
      Centers, which serve people with disabilities, have a philosophy that emphasizes
      consumer control and peer mentoring. However, the aging service delivery
      philosophy is based in a case management or medical model in which the role of
      consumers directing their services is less pronounced. Using institutional logics
      theory and a qualitative research design, this study explored whether a unified
      service delivery philosophy for ADRCs was emerging. Based on focus groups and
      questionnaires with staff from ADRCs, findings revealed that competing service
      delivery models continue to operate in the aging and disability fields.

PMID- 29064775
TI  - USPIO-positive MS lesions are associated with greater tissue damage than
      gadolinium-positive-only lesions during 3-year follow-up.
AB  - BACKGROUND: Identifying in vivo the processes that determine lesion severity in
      multiple sclerosis (MS) remains a challenge. OBJECTIVES: To describe the dynamics
      of ultrasmall superparamagnetic iron oxide (USPIO) enhancement in MS lesions and
      the relationship between USPIO enhancement and microstructural changes over 3
      years. METHODS: Lesion development was assessed at baseline, Months 3, 6, and 9,
      using magnetic resonance imaging (MRI) with gadolinium and USPIO. Microstructural
      changes were assessed at baseline, Months 3, 6, 9, 12, 18, 24, and 36, using
      relaxometry, magnetization transfer, and diffusion-weighted imaging. RESULTS: We
      included 15 patients with clinically isolated syndrome. In the 52 MRI scans
      acquired with USPIO, 22 lesions were USPIO and gadolinium positive, and 44 were
      USPIO negative but gadolinium positive. Lesions no longer exhibited sustained
      USPIO enhancement 3 months later. At baseline, lesions that were both USPIO and
      gadolinium positive had lower magnetization transfer ratio values (common
      language effect size = 0.84, p = 0.0005) and lower fractional anisotropy values
      (0.83, p = 0.001) than gadolinium-positive-only lesions. USPIO-positive lesions
      remained associated with greater damage than gadolinium-positive-only lesions
      throughout the 3-year follow-up. CONCLUSION: USPIO enhancement, mainly reflecting
      monocyte infiltration, is transient and is associated with persistent tissue
      damage after 3 years.

PMID- 29064776
TI  - Carotid stenosis - basing treatment on individual patients' needs. Optimal
      medical therapy alone or accompanied by stenting or endarterectomy.
AB  - Though carotid artery stenosis is a known origin of stroke, risk assessment and
      treatment modality are not yet satisfactorily established. Guideline updates
      according to latest evidence are expected shortly. Current clinical weakness
      concerns in particular the identification of "at-risk" patients. Beside the
      symptomatic status and the degree of stenosis, further signs of unstable plaque
      on carotid and cerebral imaging should be considered. Moreover, medical and
      endovascular therapy are continuously improving. Randomized trials and meta
      analyses have shown similar long-term results for protected carotid artery
      stenting and endarterectomy. However, endovascular revascularization was
      associated with an increased 30-day rate of minor strokes. Newly developed
      embolic protection devices could possibly compensate for this disadvantage.
      Furthermore, high-level optimal medical therapy alone is currently being
      evaluated comparatively. We assume that a comprehensive evaluation of plaque
      vulnerability, serious consideration of advanced embolic protection, and more
      space for optimal medical therapy alone according to latest evidence, will
      benefit patients with carotid stenosis.

PMID- 29064777
TI  - Mother of Berries, ACDC, or Chocolope: Examination of the Strains Used by Medical
      Cannabis Patients in New England.
AB  - Medical marijuana patients often believe that specific strains are more
      efficacious at treating their conditions. The goals of this investigation were to
      determine: (1) how many strains of cannabis are there; (2) which strains are used
      by medical cannabis (MC) patients; and (3) are there any differences in the
      strains used by patient condition? Study I involved quantifying the number of
      strains listed in the online database leafly.com and categorizing these by
      whether the strain name included a gustatory component. MC patients (N = 455)
      from New England completed an anonymous online survey about their medical history
      and strain preferences in Study II. There were 1,987 strains listed. Hybrids were
      significantly more likely than Cannabis indica strains to have a gustatory title.
      Strain preferences were highly state/dispensary specific with one-fifth of MC
      patients in Maine preferring Mother of Berries (M.O.B., 21.5%). Many respondents
      mentioned that they had developed a time-dependent pattern with sativa use during
      the day and an indica for nighttime use and for improving sleep. There is some
      general consistency across dispensaries in that hybrid strains and C. indica were
      most common. Further longitudinal and controlled investigations are necessary to
      identify the strains that are most efficacious for specific conditions.

PMID- 29064779
TI  - Anatomic Customization of Root-Analog Dental Implants With Cone-Beam CT and
      CAD/CAM Fabrication: A Cadaver-Based Pilot Evaluation.
AB  - Existing root-analog dental implant systems have no standardized protocols
      regarding retentive design, surface manipulation, or prosthetic attachment design
      relative to the site's unique anatomy. Historically, existing systems made those
      design choices arbitrarily. For this report, strategies were developed that
      deliberately reference the adjacent anatomy, implant and restorable path of draw,
      and bone density for implant and retentive design. For proof of concept, dentate
      arches from human cadavers were scanned using cone-beam computed tomography and
      then digitally modeled. Teeth of interest were virtually extracted and
      manipulated via computer-aided design to generate root-analog implants from
      zirconium. We created a stepwise protocol for analyzing and developing the
      implant sites, implant design and retention, and prosthetic emergence and
      connection all from the pre-op cone-beam data. Root-analog implants were placed
      at the time of extraction and examined radiographically and mechanically
      concerning ideal fit and stability. This study provides proof of concept that
      retentive root-analog implants can be produced from cone-beam data while
      improving fit, retention, safety, esthetics, and restorability when compared to
      the existing protocols. These advancements may provide the critical steps
      necessary for clinical relevance and success of immediately placed root-analog
      implants. Additional studies are necessary to validate the model prior to
      clinical trial.

PMID- 29064778
TI  - Studies of Physical Education in the United States Using SOFIT: A Review.
AB  - PURPOSE: An objective database for physical education (PE) is important for
      policy and practice decisions, and the System for Observing Fitness Instruction
      Time (SOFIT) has been identified as an appropriate surveillance tool for PE
      across the nation. The purpose of this review was to assess peer-reviewed studies
      using SOFIT to study K-12 PE in U.S. schools. METHOD: The Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses informed the review, and 10
      databases were searched for English-language articles published through 2016. A
      total of 704 records identifying SOFIT were located, and 137 full texts were
      read. Two authors reviewed full-text articles, and a data extraction tool was
      developed to select studies and main topics for synthesis. RESULTS: Twenty-nine
      studies that included direct observations of 12,256 PE lessons met inclusion
      criteria; 17 were conducted in elementary schools, 9 in secondary schools, and 3
      in combined-level schools. Inconsistent reporting among studies was evident,
      including not all identifying the number of classes and teachers involved. All
      studies reported student physical activity, but fewer reported observer
      reliabilities (88%), lesson context (76%), teacher behavior (38%), and PE dosage
      (34%). The most frequently analyzed independent variables were teacher
      preparation (48%), lesson location (38%), and student gender (31%). CONCLUSIONS:
      SOFIT can be used reliably in diverse settings. Inconsistent reporting about
      study procedures and variables analyzed, however, limited comparisons among
      studies. Adherence to an established protocol and more consistent reporting would
      more fully enable the development of a viable database for PE in U.S. schools.

PMID- 29064781
TI  - Dynamics of Learning in MLP: Natural Gradient and Singularity Revisited.
AB  - The dynamics of supervised learning play a main role in deep learning, which
      takes place in the parameter space of a multilayer perceptron (MLP). We review
      the history of supervised stochastic gradient learning, focusing on its singular
      structure and natural gradient. The parameter space includes singular regions in
      which parameters are not identifiable. One of our results is a full exploration
      of the dynamical behaviors of stochastic gradient learning in an elementary
      singular network. The bad news is its pathological nature, in which part of the
      singular region becomes an attractor and another part a repulser at the same
      time, forming a Milnor attractor. A learning trajectory is attracted by the
      attractor region, staying in it for a long time, before it escapes the singular
      region through the repulser region. This is typical of plateau phenomena in
      learning. We demonstrate the strange topology of a singular region by introducing
      blow-down coordinates, which are useful for analyzing the natural gradient
      dynamics. We confirm that the natural gradient dynamics are free of critical
      slowdown. The second main result is the good news: the interactions of elementary
      singular networks eliminate the attractor part and the Milnor-type attractors
      disappear. This explains why large-scale networks do not suffer from serious
      critical slowdowns due to singularities. We finally show that the unit-wise
      natural gradient is effective for learning in spite of its low computational
      cost.

PMID- 29064780
TI  - The relationship between holding back from communicating about breast concerns
      and anxiety in the year following breast biopsy.
AB  - PURPOSE: Evidence suggests open communication about breast cancer concerns
      promotes psychological adjustment, while holding back can lead to negative
      outcomes. Little is known about the relationship between communication and
      distress following breast biopsy. Design/ Sample: Women (N = 128) were assessed
      at the time of breast biopsy and again one week and three, six, and 12 months
      post-result. METHODS: Linear mixed modeling examined relationships between
      holding back and anxiety for women with benign results (n = 94) or DCIS/invasive
      disease (n = 34) following breast biopsy. FINDINGS: Anxiety increased among women
      with a benign result engaging in high but not low or average levels of holding
      back. Holding back was positively associated with anxiety post-result in breast
      cancer survivors, with anxiety decreasing over time. Conclusions/ Implications:
      Interventions to enhance communication are warranted, and knowledge of the
      differences among women with benign results and/or DCIS/invasive disease may
      allow for the development of tailored interventions.

PMID- 29064782
TI  - Capturing Spike Variability in Noisy Izhikevich Neurons Using Point Process
      Generalized Linear Models.
AB  - To understand neural activity, two broad categories of models exist: statistical
      and dynamical. While statistical models possess rigorous methods for parameter
      estimation and goodness-of-fit assessment, dynamical models provide mechanistic
      insight. In general, these two categories of models are separately applied;
      understanding the relationships between these modeling approaches remains an area
      of active research. In this letter, we examine this relationship using
      simulation. To do so, we first generate spike train data from a well-known
      dynamical model, the Izhikevich neuron, with a noisy input current. We then fit
      these spike train data with a statistical model (a generalized linear model, GLM,
      with multiplicative influences of past spiking). For different levels of noise,
      we show how the GLM captures both the deterministic features of the Izhikevich
      neuron and the variability driven by the noise. We conclude that the GLM captures
      essential features of the simulated spike trains, but for near-deterministic
      spike trains, goodness-of-fit analyses reveal that the model does not fit very
      well in a statistical sense; the essential random part of the GLM is not
      captured.

PMID- 29064783
TI  - Mechanism-Based and Input-Output Modeling of the Key Neuronal Connections and
      Signal Transformations in the CA3-CA1 Regions of the Hippocampus.
AB  - This letter examines the results of input-output (nonparametric) modeling based
      on the analysis of data generated by a mechanism-based (parametric) model of CA3
      CA1 neuronal connections in the hippocampus. The motivation is to obtain
      biological insight into the interpretation of such input-output (Volterra
      equivalent) models estimated from synthetic data. The insights obtained may be
      subsequently used to interpretat input-output models extracted from actual
      experimental data. Specifically, we found that a simplified parametric model may
      serve as a useful tool to study the signal transformations in the hippocampal CA3
      CA1 regions. Input-output modeling of model-based synthetic data show that
      GABAergic interneurons are responsible for regulating neuronal excitation,
      controlling the precision of spike timing, and maintaining network oscillations,
      in a manner consistent with previous studies. The input-output model obtained
      from real data exhibits intriguing similarities with its synthetic-data
      counterpart, demonstrating the importance of a dynamic resonance in the
      system/model response around 2 Hz to 3 Hz. Using the input-output model from real
      data as a guide, we may be able to amend the parametric model by incorporating
      more mechanisms in order to yield better-matching input-output model. The
      approach we present can also be applied to the study of other neural systems and
      pathways.

PMID- 29064784
TI  - Balancing New against Old Information: The Role of Puzzlement Surprise in
      Learning.
AB  - Surprise describes a range of phenomena from unexpected events to behavioral
      responses. We propose a novel measure of surprise and use it for surprise-driven
      learning. Our surprise measure takes into account data likelihood as well as the
      degree of commitment to a belief via the entropy of the belief distribution. We
      find that surprise-minimizing learning dynamically adjusts the balance between
      new and old information without the need of knowledge about the temporal
      statistics of the environment. We apply our framework to a dynamic decision
      making task and a maze exploration task. Our surprise-minimizing framework is
      suitable for learning in complex environments, even if the environment undergoes
      gradual or sudden changes, and it could eventually provide a framework to study
      the behavior of humans and animals as they encounter surprising events.

PMID- 29064785
TI  - Predictive Coding for Dynamic Visual Processing: Development of Functional
      Hierarchy in a Multiple Spatiotemporal Scales RNN Model.
AB  - This letter proposes a novel predictive coding type neural network model, the
      predictive multiple spatiotemporal scales recurrent neural network (P-MSTRNN).
      The P-MSTRNN learns to predict visually perceived human whole-body cyclic
      movement patterns by exploiting multiscale spatiotemporal constraints imposed on
      network dynamics by using differently sized receptive fields as well as different
      time constant values for each layer. After learning, the network can imitate
      target movement patterns by inferring or recognizing corresponding intentions by
      means of the regression of prediction error. Results show that the network can
      develop a functional hierarchy by developing a different type of dynamic
      structure at each layer. The letter examines how model performance during pattern
      generation, as well as predictive imitation, varies depending on the stage of
      learning. The number of limit cycle attractors corresponding to target movement
      patterns increases as learning proceeds. Transient dynamics developing early in
      the learning process successfully perform pattern generation and predictive
      imitation tasks. The letter concludes that exploitation of transient dynamics
      facilitates successful task performance during early learning periods.

PMID- 29064786
TI  - Improved Perceptual Learning by Control of Extracellular GABA Concentration by
      Astrocytic Gap Junctions.
AB  - Learning of sensory cues is believed to rely on synchronous pre- and postsynaptic
      neuronal firing. Evidence is mounting that such synchronicity is not merely
      caused by properties of the underlying neuronal network but could also depend on
      the integrity of gap junctions that connect neurons and astrocytes in networks
      too. In this perspective, we set out to investigate the effect of astrocytic gap
      junctions on perceptual learning, introducing a model for coupled neuron
      astrocyte networks. In particular, we focus on the fact that astrocytes are rich
      of GABA transporters (GATs) which can either uptake or release GABA depending on
      the astrocyte membrane potential, which is a function of local neural activity.
      We show that GABAergic signaling is a crucial component of intracolumnar neuronal
      synchronization, thereby promoting learning by neurons in the same cell assembly
      that are activated by a shared sensory cue. At the same time, we show that this
      effect can critically depend on astrocytic gap junctions insofar as these latter
      could synchronize extracellular GABA levels around many neurons and throughout
      entire cell assemblies. These results are supported by extensive computational
      arguments and predict that astrocytic gap junctions could improve perceptual
      learning by controlling extracellular GABA.

PMID- 29064787
TI  - Temporal Causal Inference with Time Lag.
AB  - Accurate causal inference among time series helps to better understand the
      interactive scheme behind the temporal variables. For time series analysis, an
      unavoidable issue is the existence of time lag among different temporal
      variables. That is, past evidence would take some time to cause a future effect
      instead of an immediate response. To model this process, existing approaches
      commonly adopt a prefixed time window to define the lag. However, in many real
      world applications, this parameter may vary among different time series, and it
      is hard to be predefined with a fixed value. In this letter, we propose to learn
      the causal relations as well as the lag among different time series
      simultaneously from data. Specifically, we develop a probabilistic decomposed
      slab-and-spike (DSS) model to perform the inference by applying a pair of
      decomposed spike-and-slab variables for the model coefficients, where the first
      variable is used to estimate the causal relationship and the second one captures
      the lag information among different temporal variables. For parameter inference,
      we propose an efficient expectation propagation (EP) algorithm to solve the DSS
      model. Experimental results conducted on both synthetic and real-world problems
      demonstrate the effectiveness of the proposed method. The revealed time lag can
      be well validated by the domain knowledge within the real-world applications.

PMID- 29064789
TI  - [Estimation of mercury in the urine of cigarette smokers].
AB  - INTRODUCTION: Cigarette smoking is one of the most common habits of the modern
      world. According to a NATPOL PLU study, every third adult Pole is dependent on
      nicotine. Tobacco smoke contains about 5,000 components, of which over 1,000 are
      very toxic chemical substances (3,4-benzopyrene, heavy metals, free radicals,
      hydrogen cyanide, nitrogen oxides and N-nitrosamines). Exposure to tobacco smoke
      is an example of a complex, with a significant number of interactions. THE AIM OF
      THE STUDY: To assess the concentration of copper in the urine of smokers. Based
      on the results, an attempt was made to determine whether smoking can affect the
      level of copper in the body. MATERIAL AND METHODS: The study involved 170 healthy
      volunteers, 99 smokers and 71 non-smokers (control group). The age of patients in
      both groups were in the range of 20-60 years. The mean age for men and women was
      41 years. The average length of cigarette smoking was 18 years for women and 21
      years for men, and the number of cigarettes smoked 1-40 / 24. The urine
      concentrations of Cu were determined by atomic absorption spectrometry (AAS) and
      serum creatinine kinetic method using a set of BIOLAB. Cu concentration in urine
      was expressed in mg / g creatinine. RESULTS: Smokers were found to have reduced
      levels of copper in the urine, depending on sex, age and brand of cigarettes. In
      male smokers, copper concentration in the urine was dependent on age and time of
      smoking, whereas among women this relationship was not observed. CONCLUSIONS:
      Cigarette smoking significantly influences the level of copper in the urine. Both
      female and male smokers showed reduced levels of copper in the urine, which may
      indicate its increased accumulation in the body. Excessive accumulation of copper
      is very dangerous since it may exhibit toxic effects towards many organs and
      systems.

PMID- 29064790
TI  - [The prognostic value of kcnq1 gene mutations in patients after myocardial
      infarction].
AB  - INTRODUCTION: Ion channel gene mutations are risk factors for SCD. THE AIM: To
      assess the prognostic value of A2753831C, C2505734T, C2505846A, G2753881A,
      T2755854C and T2755875G mutations in the KCNQ1 gene in patients after MI.
      MATERIAL AND METHODS: The study group of 100 patients after MI was divided into
      two groups: patients with mutations (n=23) and patients without mutations (n=77).
      The subjects underwent physical examinations, laboratory tests, ECG, Holter ECG
      and echocardiography. The examinations were repeated every 12 months. Cardiac
      events including deaths occurred during the observation period. RESULTS: The mean
      observation time was 8 +/- 4,3 years. KCNQ1 gene mutations were found in 23
      subjects and were four times more frequent in men than in women. Parameters such
      as QRS >= 110 ms, QTc >= 440 ms, VEBs >= 100 per 24 hours, nsVT and LVEF <=40%
      showed statistically significant differences between the group of patients who
      died and the group of patients who survived. LVEF <= 40% and VEBs >= 100/24 h
      were the factors that correlated the most with deaths. KCNQ1 gene mutations, PQ
      interval >= 200ms and QTd >= 60ms had no impact on death. CONCLUSIONS: The
      occurrence of KCNQ1 gene mutations in patients after MI is higher in men than in
      women. The presence of KCNQ1 gene mutations is not an additional risk factor for
      increased mortality in patients after MI. LVEF <=40% and VES >=100/24 h have a
      significant prognostic value in predicting deaths in patients after MI.

PMID- 29064788
TI  - Plasma Metal Concentrations and Incident Coronary Heart Disease in Chinese
      Adults: The Dongfeng-Tongji Cohort.
AB  - BACKGROUND: Circulating metals from both the natural environment and pollution
      have been linked to cardiovascular disease. However, few prospective studies have
      investigated the associations between exposure to multiple metals and incident
      coronary heart disease (CHD). OBJECTIVES: We conducted a nested case-control
      study in the prospective Dongfeng-Tongji cohort, to investigate the prospective
      association between plasma metal concentrations and incident CHD. METHODS: A
      total of 1,621 incident CHD cases and 1,621 controls free of major cardiovascular
      disease at baseline and follow-up visits were matched on age (+/-5 years) and
      sex. We measured baseline fasting plasma concentrations of 23 metals and used
      conditional logistic regression models to estimate odds ratios (ORs) of CHD for
      metal concentrations categorized according to quartiles in controls. RESULTS:
      Five metals (titanium, arsenic, selenium, aluminum, and barium) were
      significantly associated with CHD based on trend tests from single-metal
      multivariable models adjusted for established cardiovascular risk factors. When
      all five were included in the same model, adjusted ORs for barium and aluminum
      were close to the null, whereas associations with titanium, arsenic, and selenium
      were similar to estimates from single-metal models, and ORs comparing extreme
      quartiles were 1.32 (95% CI: 1.03, 1.69; p-trend=0.04), 1.78 (95% CI: 1.29, 2.46;
      p-trend=0.001), and 0.67 (95% CI: 0.52, 0.85; p-trend=0.001), respectively.
      CONCLUSIONS: Our study suggested that incident CHD was positively associated with
      plasma levels of titanium and arsenic, and inversely associated with selenium.
      Additional research is needed to confirm these findings in other populations.
      https://doi.org/10.1289/EHP1521.

PMID- 29064791
TI  - Effect of quercetin on parameters of central hemodynamics and myocardial ischemia
      in patients with stable coronary heart disease.
AB  - THE AIM: The aim of our research was to study the effect of quercetin on
      parameters of central hemodynamics and myocardial ischemia in patients with
      stable coronary heart disease (CHD). MATERIAL AND METHODS: The research involved
      85 patients with CHD: stable angina pectoris, FC II, and 30 healthy individuals
      made up the control group. After 1.5 months of stabilizing therapy (beta
      blockers, statins, aspirin) patients with CHD were randomized into 2 groups - the
      research group (30 people) and the comparison group (55 people). Quercetin at a
      dose of 120 mg per os daily was added to standard treatment of the patients of
      the research group (with CHD), patients of the comparison group continued
      receiving the same treatment. The day before randomization and 2 months after
      prescribing differentiation therapy to the patients, echocardiography (echo) and
      24 hour Holter ECG monitoring were made. RESULTS: Clinical evaluation of
      echocardiography revealed that diastolic dysfunction of the left ventricle (LV)
      had been found in 100% of patients studied: in 97.6% - in the form of violation
      of relaxation (type I), in 2.4% of patients - in the form of pseudonormalization
      (type II). The 24 hour Holter ECG monitoring revealed episodes of myocardial
      ischemia (10.7+2.7 episodes a day), premature atrial contractions (PACs) and
      premature ventricular contractions (PVCs) in patients with stable CHD. After a
      two-month term of therapy in patients of both research and comparison groups left
      ventricular systolic function in terms of ejection fraction (EF) of LV
      significantly improved (by 4.5% and 3.2% respectively). LV diastolic function
      improved in both groups in terms of the ratio of the phases of the transmitral
      flow E/A, also IVRT significance decreased (p<0.05). DT value dropped
      significantly influenced by quercetin, in the comparison group it didn't change.
      According to the 24 hour Holter ECG monitoring, the total time and number of
      episodes of ST segment depression decreased with dominative results in quercetin
      group. PVC number was significantly reduced only by influence of therapy with
      quercetin (?=0.0022). CONCLUSIONS: The data have shown cardioprotective
      properties of quercetin in conditions of CHD.

PMID- 29064792
TI  - Anti-inflammatory and endothelium protective effect of long-term pioglitazone
      intake in patients suffering from bronchial asthma concurrent with ischemic heart
      disease.
AB  - INTRODUCTION: Treatment of co-morbidities, including bronchial asthma (BA) and
      coronary heart disease (CHD), is a relevant issue of modern therapy. The aim of
      the research is to study the impact of long-term intake of pioglitazone on the
      development of inflammation and ED in patients with BA concurrent with CHD.
      MATERIAL AND METHODS: The clinical study involved 50 people aged 40-75 who
      suffered from asthma concurrent with CHD. On the first day of the study, blood
      samples were collected and clinical examinations were performed, after which
      patients were randomized and divided into the control group who continued to
      receive only the standard therapy, and the study group, who received pioglitazone
      (Pioglar, Ranbaxy, India) 15 mg once a day along with comprehensive therapy. Re
      examination was carried out in 6 months. RESULTS: It has been found that
      inclusion of pioglitazone in the course of standard therapy in patients with
      asthma concurrent with coronary heart within 6 months is a more efficient scheme
      than the course of standard therapies. According to the data obtained from the
      patients, there was a significant decrease in respiratory rate (p<0.01), levels
      of systolic blood pressure (p<0.001) and diastolic blood pressure (p<0.001).
      Administering pioglitazone contributed to the improvement of respiratory function
      and airflow obstruction, increased FEV1 performance (p<0.01) and Tiffeneau index
      (p<0.05). In patients of the study group, intake of pioglitazone helped to reduce
      angina. Intake of pioglitazone showed a significant decrease in the frequency of
      angina pectoris FC II (p<0.05) and a significant increase in the frequency of
      angina FC I (p<0.05), increase in the rate of threshold load power (p<0.05). In
      assessing endothelium-dependent vasodilation of the brachial artery, it has been
      noted that intake of pioglitazone by patients with asthma concurrent with
      coronary heart disease resulted in a statistically significant increase in the
      diameter of the brachial artery by an average of 4% (p<0.0001), the maximum blood
      flow velocity (TAMX) by an average of 40 % (p<0.0001), Delta% diameter increase
      in the brachial artery (p<0.0001), and achieved positive indicators of RI
      (p<0.0001). In assessing endothelium-dependent vasodilation of brachial artery in
      patients treated with pioglitazone, there was a significant increase in the
      diameter of brachial artery on average by 5% (p<0.0001) after taking
      nitroglycerin, an increase in ?% diameter of brachial artery (p<0.0001) and RI
      (p<0.0001). Inclusion of pioglitazone in the complex therapy for 6 months
      resulted in a significant decrease in the index of systemic inflammation hs-CRP
      (p<0.0001) and adhesion marker sVCAM-1 (p<0.0001), total cholesterol (p<0.001),
      triglycerides (p<0.001). CONCLUSION: Thus, these data demonstrate the anti
      inflammatory and endothelium protective effects of pioglitazone against the
      background of standard therapy in patients with BA concurrent with CHD within 6
      months, which may enhance the clinical efficacy in the treatment of these
      diseases.

PMID- 29064793
TI  - [Experience and comparison of antihypertensive effect of ace inhibitor spirapril
      and calcium antagonist amlodipinein standard and chronotherapeutic prescription
      mode].
AB  - Arterial pressure is an effect of many physiologic processes of organism effected
      by daily rhytmus. The introduction of round the 24-hour monitoring of arterial
      pressure enabled to detect arterial pressure circular fluctuation. Chronotherapy
      with the application of amlodipin and spirapril due to the data of round the 24
      hour arterial pressure monitoring increases the effectiveness of antihypertensive
      therapy.

PMID- 29064794
TI  - [Role of c+70g single nucleotide polymorphism of endothelin receptor a gene in
      the development of ischemic atherothrombotic stroke].
AB  - INTRODUCTION: Endothelial dysfunction is the basic pathogenic development
      mechanism of ischemic atherothrombotic stroke (IAS). One of the reasons for
      changes of endothelin structure and properties and its receptor can be genetic
      polymorphism of their genes. AIM: Study of C+70G polymorphic variant associations
      of endothelin receptor A gene (EDNRA) with IAS development became the goal of
      research. MATERIAL AND METHODS: Venous blood of 170 patients with IAS and 124
      persons without cerebrovascular pathology was used for the research. The groups
      did not differ in the ratio of two sexes (P = 0,294 for the ?2-test), but the
      average age of the first group (76,7 +/- 0,93 years) was significantly higher
      than that of the second one (P < 0,001). Determination of allelic variant of
      EDNRA gene by C+70G polymorphism was carried out using method of polymerase chain
      reaction with further analysis of restriction fragment length. RESULTS: As a
      result of the conducted genotyping, it has been discovered that homozygote
      correlation by the main allele (CC), heterozygotes (CG) and homozygotes by minor
      allele (GG) does not differ authentically in patients with IAS and control group
      (24.1 %, 57.6 %, 8.2 % against 29.0 %, 50.0 %, 21.0 %; ? = 0.426). It is shown
      that association of the studied genetic marker with the scope of brain damage,
      localization of atherothrombotic process, course severity, recurrence and
      neurological manifestations of IAS. CONCLUSIONS: There is no association between
      the C+70G polymorphism of the EDNRA gene and the development of IAS and its
      clinical characteristics.

PMID- 29064795
TI  - The impact of emergent infections on the fetal state.
AB  - THE AIM: To study the impact of emergent infections (human herpesvirus type 6) on
      the fetal state. MATERIALS AND METHODS: The study involved examination of 90
      pregnant women in the 2nd and 3rd trimesters of gestation (Group 1 (25 pregnant)
      consisted of patients with a viral infection, CMV carriers, Group 2 (25 pregnant)
      included women with a viral infection, herpes simplex virus types 1/2, Group 3
      amounted for 20 patients with a viral infection, herpes simplex virus type 6,
      Group 4 comprised 20 patients with normal pregnancy and no signs of infection.
      Concentration of IgM and IgG to herpes simplex virus types 1/2, IgM and IgG to
      herpesvirus type 6 in venous blood of the pregnant was determined by enzyme
      immunoassay. Giant cells typical for CMV were determined by cytological
      examination of saliva sediment. All the pregnant underwent ultrasound
      somatogenetic examination, Doppler evaluation of maternal-placental-fetal
      hemodynamics and biophysical profile (BPP) assessment. Results and their
      discussion: Ultrasound examination of Group 1, 2 and 3 pregnant showed signs of
      intrauterine infection. Pregnant women with a viral infection were found to have
      intrauterine growth retardation (IUGR) and Group 3 patients more commonly had
      symmetrical 3rd degree IUGR. BPP indices showed initial signs of fetal distress
      in 5 (20%) Group 1 pregnant, 7 (27%) Group 2 pregnant and 11 (55%) Group 3
      pregnant women. Doppler examination of uterine-feto-placental hemodynamics
      revealed a more pronounced increase in vascular resistance indices in Group 3
      patients. CONCLUSIONS: Emergent infections (herpesvirus type 6) of pregnant
      trigger more pronounced changes in the feto-placental system than other viral
      infections. Herpesvirus type 6 is a common cause of fetal state deterioration,
      which manifests in intrauterine growth retardation, changes in biophysical
      profile and hemodynamic disorders in the mother-placenta-fetus system.

PMID- 29064796
TI  - Association between depressive symptoms and cognitive impairment in patients with
      metabolic syndrome.
AB  - INTRODUCTION: Metabolic dysregulation is intimately associated with wide array of
      seemingly unrelated disorders, including cognitive impairment and depression. The
      aim was: to identify special characteristic features of depressive disorder in
      patients with metabolic syndrome (Mets); to identify possible association between
      depressive disorder (DD) and cognitive impairment in patients with Mets; to
      establish whether metabolic syndrome and its components are associated with
      severity of DD. MATERIALS AND METHODS: The study group consisted of 108 patients
      with depressive disorders aged from 45 to 84 years. All patients were divided
      into two groups: main- with Mets (n=60) and control - without metabolic syndrome
      (n=48), comparable for age, sex and level of education. The examination consisted
      of physical and neurological examination and the application of
      neuropsychological tests (Mini-Mental State Examination/MMSE, Hamilton Depression
      Rating Scale / HAM-D) magnetic resonance imaging and laboratory tests. RESULTS:
      It has been found more pronounced severity of depressive disorder (DD) in
      patients with Mets compared with patients without it (p<0,05). In the group of
      patients with Mets there was significantly higher incidence of somatic anxiety (p
      <0,01), hypochondria (p <0,05), reduced criticality (p <0,05) compared with
      patients without Mets. It has been found significantly higher incidence of
      dementia in patients with DD and Mets comparing with patients with DD without
      Mets (p<0,05). Statistically significant negative correlation was found between
      the total score on the Hamilton scale and the total MMSE score (r = -0,56, p
      <0.05) only in the group of patients with Mets. Of all Mets components a reliable
      positive correlation was found only between high triglyceride levels of blood and
      the total Hamilton scale score (rs = 0,27). CONCLUSIONS: Our study adds to the
      mounting evidence that links depression and Mets. Some specific features of DD in
      patients with MetS were established. The severity of DD was significantly
      associated with severity of cognitive impairment in patients with Mets. Of all
      components of Mets, only elevated levels of triglycerides of blood was
      significantly associated with the severity of DD in our maim group of patients.

PMID- 29064797
TI  - The use of injection-corrosive method in the study of extraorganic bloodstream of
      human intact stomach.
AB  - INTRODUCTION: Functional and morphological state of the organs and tissues mainly
      depends on the adequate blood supply and lymph movement, function of which is
      integrated by the nervous system. A crucial link in the morphogenesis of the
      gastric lesions is the intensity of vascularization, as well as the fact that in
      its venous part the gastric bloodstream is almost entirely included into the
      portal vein system. Knowledge of the anatomy of the normal human stomach
      conditions is of indispensable practical value, since they are required for the
      proper interpretation of the pathological changes occurred in it. THE AIM: To
      obtain the spatial visual information about the angioarchitecture of the
      extraorganic bloodstream of human intact stomach deep in the gastric wall.
      MATERIALS AND METHODS: 10 post-autopsy adult total stomach specimens of patients,
      died for the reasons not associated with manifested gastrointestinal diseases
      have been analyzed. The specimens were extracted during the dissection together
      with portions of lesser and greater omentum, and segment of aorta with celiac
      trunk. To neutralize the acidic contents of the stomach, its cavity was washed by
      4% sodium bicarbonate solution with subsequent wash in warm running water. The
      vascular injection method with subsequent corrosion of soft tissues was used in
      investigation of gastric bloodstream. RESULTS AND CONCLUSIONS: On the basis of
      the investigations the advantages of the countercurrent-crossing method of
      injection of extraorganic vessels to fill the bloodstream of human stomach have
      been discussed. Positive results of the suggested technique for morphological
      study of blood vessels have been noted. The three-dimensional spatial
      organization of the extraorganic bloodstream of the intact stomach can be studied
      on the basis of the injection-corrosive casts. Thus, the use of the suggested
      method enables to obtain the fine three-dimensional reproduction of extraorganic
      bloodstream of the human stomach. The obtained high-quality casts, in turn, are
      used for the subsequent morphological studies of the intact stomach.

PMID- 29064798
TI  - Anhedonia at experimental models of chronic stress and its correction.
AB  - INTRODUCTION: Different types of chronic stress lead to neurotic and depressive
      disorders. Key symptoms of these disorders are anhedonia and correction of which
      will indicate the efficacy of proposed therapy. The aim of the paper is to
      investigate the influence of amide 2-hydroxy-N-naftalen-1-il-2-(2-oxo-1,2-dihidro
      indole-3-iliden) and ethyl ether 4-[2-hydroxy-2-(2-oxo-1,2-dihidro-indole-3
      iliden)-acetamin]-butyric acid on anhedonia after the experimental neurosis and
      chronic moderate stress in rats. MATERIALS AND METHODS: It was studied the
      influence of therapeutic and preventive administration of substances 18 and E-38
      in the dosage of 12mg/kg during chronic mild stress "conflict of afferent
      activation" during 30 days and depression-like behavior chronic mild stress that
      modeled 8 weeks. Results of investigation: Experimental neurosis caused decrease
      of number of comings to drinking-bowl, decrease of total number of drank sucrose
      and decrease of the percent of drank water with sugar in comparison with intact
      animals. Analogical but more significant changes were noticed during depression
      like behavior. The use of amide 2-oxoindolin-3-glyoxylic acid based on neurosis
      counters effectively the development of anhedonia. Substance 18 increased the
      number of comings to drinking-bowl with sucrose and increased the amount of the
      number of drank water with sucrose in comparison with control pathology without
      correction. The substance possibly assists in use of solution with sucrose among
      water and does not compromise reference-preparation such as diazepam. The
      administration of ethyl ether of 2-oxoindolin-3-glyoxylic acid at chronic mild
      stress possibly increased the number of comings to the drinking-bowl and
      increased the number of drank sucrose in comparison with control pathology and it
      was more effective than imipramine and countered anhedonia. CONCLUSIONS: It was
      indicated that during 30 day experimental neurosis and 8 week depression-like
      behavior cause the development of anhedonia. Therapeutic use of amide 2-hydroxy-N
      naftalen-1-il-2-(2-oxo-1,2-dihidro-indole-3-iliden) and ethyl ether 4-[2-hydroxy
      2-(2-oxo-1,2-dihidro-indole-3-iliden)-acetamin]-butyric acid corrected
      effectively anhedonia after experimental neurosis and chronic mild stress in
      rats.

PMID- 29064799
TI  - Gastroesophageal reflux disease: the results of videolaparoscopic fundoplication
      at five years after surgery.
AB  - INTRODUCTION: GERD reduces social activity and significantly affects the quality
      of life (QOL) of patients and the risk of complications (cancer of the esophagus,
      esophageal-gastric bleeding, strictures, perforation) is one of the most pressing
      problems of medicine of XXI century. The aim of the research is to evaluate the
      results of videolaparoscopic fundoplication at five years after surgery in
      patients with gastroesophageal reflux disease. MATERIAL AND METHODS: We studied
      results of videolaparoscopic antireflux surgery (VLAS) during 2009-2016 years in
      Department of Surgery and Endoscopy Faculty of postgraduate medical education
      Lviv National Medical University. We have gathered the group of 195 patients who
      underwent VLAS. RESULTS: Among the complications of GERD, Barrett's esophagus was
      diagnosed in 9 (19.6 %), peptic ulcer of the esophagus in 10 (21.7 %), peptic
      stricture of the esophagus in 4 (8.7 %), esophageal-gastric bleeding in 23 (50.0
      %) patients, including Malory-Weiss syndrome in 18, erosive ulcerous bleeding in
      5 people. In 176 (90.2 %) patients completed Nissen fundoplication, in 14 (7.2 %)
      - Toupe, 5 (2.6 %) - Dor fundoplication. We use standart surgical techniques. The
      mean operative time was 95+/-25,2 minutes. In 2 patients after surgery
      capnothorax on left side had occurred and treated. The mean hospital stay was 3+/
      2,4 days. There were no serious complications in the time of surgery and after
      it, as well as no conversions or repeated antireflux surgeries at five years
      after surgery. CONCLUSION: Videolaparoscopic antireflux surgery for GERD is an
      equally effective alternative to medical therapy and should be offered to
      appropriately selected patients by skilled surgeons.

PMID- 29064800
TI  - The relationship between colonization resistance of the oral cavity and
      individual -typological characteristics of personality: dental aspects.
AB  - INTRODUCTION: The present article deals with the role of the oral mucosa
      colonization resistance in the implementation of the influence of individual
      typological characteristics of the individual susceptibility to caries and
      inflammatory periodontal diseases. THE AIM: to study the role of colonization
      resistance of the oral mucosa in the implementation of the influence of
      individual-typological characteristics of the individual susceptibility to caries
      and inflammatory periodontal diseases. MATERIALS AND METHODS: The studies were
      conducted on 182 medical students 19-29 years old. All the examinees had a
      screening assessment of the oral mucosa colonization resistance by our own
      method, which received a patent UA 51373. CONCLUSION: It is shown that
      psychophysiological features of healthy individuals and patients with dental
      caries and gingivitis determine the level of resistance to caries and periodontal
      inflammatory diseases, deviation of personality profile towards high neuroticism
      is a risk factor for caries and gingivitis. It is reported that the highest
      resistance to caries and inflammatory periodontal disease had emotionally stable
      introverts, inflammatory periodontal disease are more common in emotionally
      unstable introverts. The authors found that oral colonization resistance is a
      predictor of the risk of caries and inflammatory periodontal diseases. Reducing
      of the oral cavity colonization resistance most commonly diagnosed in emotionally
      unstable introverts, that correlated with their low resistance to inflammatory
      periodontal diseases.

PMID- 29064801
TI  - Early enteral nutrition as a part of intencive care of abdominal surgical
      pathology.
AB  - INTRODUCTION: Patients with abdominal surgical pathology always have
      gastrointestinal failure. Under such conditions, the enteral administration of
      nutrients may be started by trophic nutrition; however, starting nutritional
      mixtures for it have not been clearly defined. The aim of this study was
      optimization of energetic and plastic supply of patients with abdominal surgical
      pathology by studying the efficacy of the clinical nutrition means. MATERIALS AND
      METHODS: An observational analytical observational prospective case-control study
      of clinical nutrition efficacy has been conducted in 112 patients aged 18 to 45,
      who underwent intencive care after urgent abdominal surgical interventions. The
      patients were divided into two groups: in the treatment group (n=64), trophic
      nutrition by a semi-elemental nutritional formula was initiated within 12 hours
      after completion of surgery, and in the control group (n=48), the conventional
      clinical nutrition tactics was used. The levels of serum albumin,
      glycosaminoglycans, alkaline phosphatase and urine diastase activities were
      assessed; the lengths of patients' stay in the intensive care unit was recorded.
      RESULTS AND CONCLUSIONS: The application of early enteral nutrition in the
      regimen of trophic nutrition with the use of a semi-elemental nutritional formula
      allowed to improve protein provision (serum albumin level - 38.68+/-1.55 g/l vs
      32.04+/-1.5 g/l) (?<0.05), to decrease the functional load on the cytoprotective
      system of the gastrointestinal mucosa (level of glycosaminoglycans 0.11+/-0.079
      g/l vs 0.181+/-0.113) (?<0.05), to decrease the severity of cholestasis (alkaline
      phosphatase activity 620.6+/- 6.22 nmol/s/l vs 723+/-7.2 nmol/s/l (?<0.05), to
      achieve relative functional rest of the pancreas (44.5+/-1.7 g/(h x l) vs 62.6+/
      2.1 g/(h x l)) (?<0.05) and allowed to decrease the length of patients' stay in
      the intensive care unit (115.9+/-2.69 hours vs 130.8+/-3.06 hours) (?<0.05).

PMID- 29064802
TI  - Functional condition of masseters muscles of patients with class ?? subdivision.
AB  - INTRODUCTION: Main functional characteristics of masticator muscles in patients
      with class ?? malocclusions is activity dominance of m. temporalis in comparison
      with m. ?asseter. We have not found datum about functional status of the
      masticators in patients with class II subdivision. THE AIM: The purpose of our
      study was to investigate the functional characteristics of m. ?asseter, m.
      temporalis in adult patients with class II subdivision malocclusion. MATERIALS
      AND METHODS: There have been carried out the surface electromyographic study of
      m. masseter, m. temporalis in 17 adult patients with class II subdivision. It was
      realized quantitative analysis of 271 electromyogram, it was determined the
      average bioelectric activity, index activity, symmetry and torsion index.
      RESULTS: It was observed predominance of the bioelectrical activity of m.
      temporales on m. masseter for all persons with class II subdivision.
      Bioelectrical activity for m. masseter was bigger on side of distal ratio and for
      m. temporales on side of neutral ratio. In class ?? subdivision right, the
      mandible was deviated to the left side and in class ?? subdivision left is
      deviated to the right side. Thus, rotational moment generated during compression
      of the jaws, causes deviation of the lower jaw to the side, with a neutral molar
      ratio. During voluntary chewing bioelectrical activity of m. masseter and m.
      temporalis was higher in the right side. CONCLUSION: In accordance with the
      functional condition of the masticatory muscles of class II subdivision is
      characterized with functional features of distal occlusion.

PMID- 29064803
TI  - Morphological substantiation for acute immobilization stress-related disorders of
      adaptation mechanisms.
AB  - INTRODUCTION: Nowadays, an individual is being constantly accompanied by stresses
      in his/her everyday life. Stress reactions, produced in the process of evolution,
      have become the organisms' response to emergency action or pathological factors
      and are the important link in adaptation process. However, the adverse course of
      stress reaction can lead to derangement of the adaptation mechanisms in the body
      and become the element of the pathogenesis of various diseases. THE AIM: The
      study was aimed at morphological substantiation of derangement of adaptation
      mechanisms in white Wistar rats caused by the acute immobilization stress.
      MATERIALS AND METHODS: 40 Wistar white male rats of 240-260 g body weight aged 8
      10 months were involved into study. 20 laboratory animals were assigned to the
      main group and the rest 20 rats formed the control (II) group. Experimental
      stress model was simulated by immobilization of rats, lying supine, for 6 hours.
      Morphological examination of heart, lungs and kidneys was carried out after
      animals' decapitation, which proved the derangement of rats' adaptation
      mechanisms caused by the acute immobilization stress. RESULTS: It has been
      established that six-hour immobility of rats, lying in the supine position, led
      to the development of destructive phenomena, hemorrhagic lesions and impaired
      hemomicrocirculation. Microscopically, the acute immobilization stress causes
      significant subendocardial hemorrhages, plethora of vessels of
      hemomicrocirculatory flow with dysdiemorrhysis, myocardial intersticium edema in
      the heart. Histologically, immobilization-induced trauma causes significant
      hemodynamic disorders, spasm of arterioles and considerable venous hyperemia,
      concomitant with microthrombosis in kidneys; at the same time dystrophic lesions
      and desquamation of epithelium of renal tubules has been observed in renal
      corpuscles. CONCLUSION: The abovementioned structural changes can contribute to
      origination and development of multiple lesions, demonstrating the
      morphologically grounded role of the acute immobilization stress as the factor
      for disorders of adaptive mechanisms.

PMID- 29064804
TI  - [Giving medico-legal opinions in cases with suspicion of medical mistake. part 2.
      Expert evidence in cases with suspicion of medical mistake - expectations,
      possibilities, threats...].
AB  - Problems of medical mistake and therapeutic failure are inextricably linked with
      realization of medical services. In recent years, mostly by the media and
      increasing demanding attitude, a rapid increase of initiated cases opened by
      judicial body in conjunction with medical mistake made by medical staff is
      observed. Making medico-legal opinions is not easy task and often face many
      difficulties. These consist of lacks in medical documentation, time rigor, formal
      tightening and need to create team that consist of both forensic medicine
      specialist and clinicians, who together shall write complex medico-legal opinion.
      This article touches the essence of the opinion-making problem in the aspect of
      medical mistake. It shows specifics of the role of forensic medicine specialist,
      his challenges and difficulties in creating opinions. The article confronts real
      possibilities of court experts with expectations of judicial body, outlining new
      challenges and dangers which court experts have to face.

PMID- 29064805
TI  - [Key minerals significant for hypothyroidism including Hashimoto's thyroiditis -
      function and presence in food].
AB  - Thyroid diseases belong to the most common disorders of the ductless glands.
      Particular attention is paid to the growing morbidity of autoimmune affliction of
      the thyroid gland, including Hashimoto's thyroiditis. The main method of
      treatment is an oral substitution of thyroid hormones. However, the literature
      pays particular attention to supporting therapy with a diet rich in components
      essential for the proper functioning of this organ.

PMID- 29064806
TI  - [Gait disturbances and falls in various types of dementias].
AB  - Dementia is a group of symptoms of damage of higher cortical functions. The
      causes of dementia include brain diseases, most often chronic and progressive,
      leading to cognitive impairment typical of these disorders. Apart from
      progressive cognitive deficits, dementias may coexist with mental disorders,
      sleep disorders, epileptic seizures, parkinsonism and other motor disorders.
      Motor disorders, including gait disturbances and falls, represent a serious
      challenge to the health of older adults and contribute to loss of mobility and
      independence. Analysis of motor disturbances in the population of healthy older
      adults and those with progressive cognitive impairment is likely to support
      effective planning of pharmacological therapies and rehabilitation for this group
      of patients.

PMID- 29064807
TI  - [Central nervous system involvement in systemic lupus erythematosus - diagnosis
      and therapy].
AB  - Nervous system involvement in lupus belongs to its severe complications and
      significantly impacts its prognosis. Neuropsychiatric lupus includes 19 disease
      manifestations concerning both central and peripheral nervous system. This paper
      presents clinical aspects of central nervous system involvement in lupus. It
      reviews its epidemiology, risk factors and principles of diagnosis and therapy.

PMID- 29064808
TI  - [The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a
      literature review].
AB  - Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous
      articular, extra-articular and systemic manifestations. The cause of rheumatoid
      arthritis is multifactorial including genetic and environmental factors. Recent
      advantages in sequencing techniques have allowed the deep characterization of the
      human microbiota. Available evidence confirms the existence of an association
      between dysbiosis and rheumatoid arthritis but it still remains unclear whether
      alterations in the microbiome are a pathogenic cause or an effect of autoimmune
      disease. In patients with rheumatoid arthritis the most supported association
      between disease and microbiota is with the oral dysbiosis usually observed in
      patients with periodontitis. Given the strong variability and abundance of
      microbes living in close relation with human host, it becomes a difficult task to
      define what should be considered the favorable microbiome. There is need for
      broader studies to establish how the human microbiome contributes to disease
      susceptibility, and to characterize the role of microbial diversity in the
      pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The
      identification of dysbiosis specific for rheumatoid arthritis and the
      understanding of the dynamic interaction between microbiota and their host may
      help in establishing an individualized management for each patient with
      rheumatoid arthritis, and achieve a better efficacy of the therapy.

PMID- 29064809
TI  - [Parathormone and vitamin d in heart failure - theoretical influence on disease
      development and potential therapy targets].
AB  - Vitamin D and parathormone (PTH) are hormones regulating calcium and phosphorus
      homeostasis. The aim of the article is to summarize the current knowledge in the
      field and to assess its impact on heart failure (HF) pathogenesis. PTH serum
      concentration being frequently elevated in patients with HF has negative impact
      on circulatory system stimulating myocardial fibrosis, wall thickening and
      reninangiotensin-aldosterone system (RAAS) activity. PTH reacts with smooth
      muscle cells receptors mediating adrenergic and chronotropic activation resulting
      in increased oxidative stress, endothelial dysfunction, intracellular calcium
      overload and has negative influence on prognosis in chronic HF patients. Vitamin
      D, which deficiency is common in developed countries, has widely distributed
      receptors including myocardium, endothelium and smooth muscle cells. Being an
      antiproliferative agent vitamin D modulates RAAS, regulates natriuretic peptides
      and myosine expression, suppresses inflammatory cytokines activity, has
      antiarrhytmic properties and increases myocardial contractility. It decreases
      arterial pressure, inhibits atherosclerosis progression and plays a protective
      role against inflammation including viral infections of cardiotropic potential.
      Optimal vitamin D serum concentration has potential protective impact on
      cardiovascular system.

PMID- 29064810
TI  - [Nonadherence and ineffective methotrexate treatment of inflammatory arthritis].
AB  - Failure to comply with treatment recommendations in chronic diseases, including
      inflammatory arthritis, is one of the main reasons why patients do not achieve
      health benefits. It is widely recognized that effective pharmacotherapy requires
      a conviction to undertake and continue. In case of methotrexate therapy failure,
      it is necessary to consider the possibility and cause for non adherence to
      treatment. In order to achieve chosen therapy goals, cooperation of patient and
      physician is essential. A review of medical literature brings up a necessity to
      consider the differences in understanding and definition of both compliance and
      adherence, and whether the failure in treatment is tied to pharmacology, or
      inadequate patient knowledge. Patient education should entail thorough
      understanding of therapy goals, the mainstay role of methotrexate in current
      strategies and the benefits of consistent treatment. Attention should be paid to
      the role of methotrexate polyglutamates in monitoring therapy effectiveness, and
      the choice between subcutaneous and oral administration. A joint consideration of
      the dosing regimen, convenient methods of administration and dispelling any
      doubts over adverse events are milestones that will translate into better
      adherence.

PMID- 29064811
TI  - [The risk of epileptic seizures during antibiotic therapy].
AB  - Numerous antibiotics may trigger epileptic seizures or status epilepticus by
      decreasing inhibitory transmission in the brain, thus lowering the seizure
      threshold. The most potent seizurogenic effect is exerted by penicillins,
      cephalosporins, fluorochinolons and carbapenems. Predisposing factors that
      facilitate development of epileptic seizures in the course of antibiotic therapy
      comprise all conditions accompanied by damage to the blood-brain barrier
      (including cerebral trauma and encephalitis), a high dose of an antibiotic or
      lack of adequate dose adjustment in patients with renal failure. A particularly
      dangerous and difficult to diagnose complication is nonconvulsive status
      epilepticus in patients treated with cephalosporins. For this reason, in case the
      patient presents with alterations of consciousness in the course of cephalosporin
      therapy, an EEG test should be performed. Some antibiotics, such as carbapenems,
      macrolides and antitubercular medications enter into pharmacokinetic interactions
      with antiepileptic agents, causing a decrease or increase in the plasma
      concentration of the latter and in consequence lead to possible epileptic
      seizures or drug-associated neurotoxicity. In patients with risk of epileptic
      seizures or with diagnosed epilepsy, one should select an antibiotic with a low
      proconvulsive potential and administer it in an adequately adjusted dose,
      especially in individuals with renal failure. Employing antibiotics interacting
      with antiepileptic medications with which the patient is treated should be
      avoided.

PMID- 29064812
TI  - [The influence of drugs used in the treatment of diabetes type 2 on the cardio
      vascular risk].
AB  - With the obesity epidemic, we observe increase in the number of people suffering
      from diabetes mellitus type 2. This illness is considered cardiovascular disease
      equivalent, so influence of drugs used to manage diabetes on cardiovascular
      outcomes is important. Below we present review of main class of drugs used in
      diabetes treatment and summingup of trials conducted with their use to evaluate
      cardiovascular risk during treatment.

PMID- 29064813
TI  - Protecting the rights of producers original medicines.
AB  - INTRODUCTION: the article analyzes the state of protection of intellectual
      property rights of original medicine producers, its accordance with international
      standards. Attention is focused on the importance of exclusivity of medicine
      market. AIM: the analysis of protection of intellectual property rights of
      medicine producers in Ukraine and determination of its conformity or non
      conformity to the international standards. MATERIAL AND METHODS: the experience
      of certain countries is analyzed in the research. Additionally, we used
      statistical data of international organizations, conclusions of experts. RESULTS:
      there are numerous cases of state registration of generic medicinal products
      using the registration information of original medicinal products and delict of
      the rights of patent holders. CONCLUSIONS: an effective mechanism of judicial
      protection of the original medicine producers' intellectual property rights from
      disorders that affect the profit was elaborated in Ukraine.

PMID- 29064815
TI  - Legal aspects of counteracting the trafficking of falsified medicines in the
      european union.
AB  - INTRODUCTION: The paper identifies key risks associated with the illegal
      production and sale of medicines. Also there were generalized features of
      criminal responsibility for acts related to the trafficking of drugs in some
      Member States of the EU and analyzed legal means of combating the falsified drugs
      today. The problem concerning falsification of medicines is particularly acute
      not only in developing countries but also in developed ones. Fake is one in ten -
      twenty drug. The largest share of falsified drugs comes from the so-called "Asian
      tigers", already from which they come to the EU market. THE AIM: In this
      publication authors have set following objectives: - to determine the risks
      associated with illegal production and sale of medicines; - organize legal means
      of combating the falsified medicines in the EU member states; - clarify features
      of criminal responsibility for acts related to the trafficking of drugs in the EU
      countries. MATERIALS AND METHODS: The article bases on the works of scholars and
      experts, statistical information and other sources. Particular attention is paid
      to the analysis of regulations of the EU institutions and national criminal laws.
      So, provisions of the criminal codes of 10 EU member states were taken into
      account. RESULTS: There is a system of legal measures which counter the
      circulation of falsified medicines in the EU and consists of general and specific
      regulatory requirements, mainly of economic and legal nature. The most important
      role among the last play package labeling requirements for drugs and license
      conditions. DISCUSSION: In the article were discussed factors that stimulate the
      production and sale of falsified drugs and the risks associated with these.
      Demarcated the concept of "falsified medicinal product", "counterfeit drug",
      "substandard drug". CONCLUSIONS: Although there are guidelines for patients to
      identify falsified drugs, still a major role in this process should play public
      authorities and enterprises. In all the countries illegal circulation of
      falsified drugs is prohibited under threat of criminal or administrative
      responsibility.

PMID- 29064814
TI  - Didactical determinants use of information and communication technology in
      process of training of future specialists.
AB  - In the article the author touches upon the subject of significance of computer
      equipment for organization of cooperation of professor and future specialists.
      Such subject-subject interaction may be directed to forming of professional
      skills of future specialists. By using information and communication technologies
      in education system range of didactic tasks can be solved. Improving of process
      of teaching of subjects in high school, self-learning future specialists,
      motivating to learning and self-learning, the development of reflection in the
      learning process. The authors considers computer equipment as instrument for
      development of intellectual skills, potential and willingness of future
      specialists to solve communicative and communication tasks and problems on the
      creative basis. Based on results of researches the author comes to certain
      conclusions about the effectiveness of usage of computer technologies in process
      of teaching future specialists and their self-learning. Improper supplying of
      high schools with computer equipment, lack of appropriate educational programs,
      professors' teachers' poor knowledge and usage of computers have negative impact
      on organization of process of teaching disciplines in high schools. Computer
      equipment and ICT in general are the instruments of development of intellectual
      skills, potential and willingness of future specialists to solve communicative
      and communication tasks and problems. So, the formation of psychosocial
      environment of development of future specialist is multifaceted, complex and
      didactically important issue.

PMID- 29064817
TI  - [Modern perspective on the development conditions and diagnosis of systemic
      sclerosis].
AB  - Systemic sclerosis (SSc) is a multisystem disorder of the connective tissue
      characterized by a great deal of heterogeneity. This variability is a result of a
      combination of vascular damage inflammation and fibrosis leading to internal
      organ complications. The pathogenesis of disorder is still unknown. A large part
      is given to genetic, epigenetic and environmental factors. There is ongoing
      research into the new cells and mediators involved in the complicated development
      of disease. The overlap of vascular, autoimmune/ inflammatory alternations and
      fibrosis causes the multidirectional and unpredictable course of disease.
      Vascular complications may dominate in one group, whereas fibrosis in others. In
      addition, the disorder is characterized by individual variability; therefore
      although certain prognostic markers do exist, the course of disorder in largely
      unpredictable. This complexity of SSc, makes it difficult in terms of diagnosis
      and activity assessment, especially in early stages. Over a number of years,
      further classification criteria, which were more sensitive and more specific,
      were developed. The 2013 European League Against Rheumatism/American College of
      Rheumatology - EULAR/ACR classification criteria for SSc, were revised to include
      diagnosis in early stages and particularly in limited SSc. Unfortunately, there
      still exist certain groups of population which do not fulfil these criteria but
      develop the disorder; therefore, the search for new diagnostic methods which
      could elevate SSc diagnosis continues.

PMID- 29064816
TI  - [Coffee drinking and health - the current state of knowledge. whether the end of
      the doubts of patients is already coming?]
AB  - The impact of drinking coffee on health is still relevant in medicine. Patients,
      as well as some doctors noticed coffee as the product which can cause or increase
      a risk a lot of health complaints. However contemporary scientific researches are
      more optimistic and revealed that coffee doesn't have such negative impact on
      health, and what's more can has beneficial action. In spite of some differences
      in findings many of them demonstrated a lack of relationship between coffee and
      blood pressure, cancers, and in case of type 2 diabetes and neurodegenerative
      diseases even a protective action is possible. Drinking moderate amount of
      coffee, brewed using filters (3-4 cups a day) is preferred. Polyphenols are the
      main of bioactive components of coffee which act as antioxidants and can explain
      a positive impact of coffee on health.

PMID- 29064818
TI  - [Dental perspective on Crohn's disease: literature review].
AB  - Crohn's disease (CD) is a chronic, idiophatic inflammatory process of the
      gastrointestinal tract and its cause remains unknown. It can affect any part of
      the digestive system, but preferentially involves the terminal part of the small
      intestine and the beginning of the large intestine. The disease course is usually
      long-term with episodes of remission and relapses. The clinical presentation of
      the disease varies and depends on the site of inflammation. Oral lesions can
      occur in 80% of pediatric and 90% of adult patients with CD. The most frequent
      are swelling of the oral mucosa with surface cobblestoning, ulcerations,
      candidiasis, angular cheilitis. The difficulty in diagnosis, resulting from the
      non-specific clinical manifestation, hamper proper diagnosis and delay the start
      of treatment. This paper presents etiology, epidemiology, clinical features and
      basic therapeutic capabilities for CD in the light of the literature. Oral
      manifestation of this disease was particularly emphasized.

PMID- 29064819
TI  - Age-related decline of the acute local inflammation response: a mitigating role
      for the adenosine A2A receptor.
AB  - Aging is accompanied by an increase in markers of innate immunity. How aging
      affects neutrophil functions remains of debate.The adenosine A2A receptor (A2AR),
      essential to the resolution of inflammation, modulates neutrophil functions. We
      sought to determine whether or not A2AR protects against the effects of aging. We
      monitored neutrophil influx, viability, and activation as well as cytokine
      accumulation in wild-type (WT) and A2AR-knockout mice (KO) at three different
      ages.Several readouts decreased with aging: neutrophil counts in dorsal air
      pouches (by up to 55%), neutrophil viability (by up to 56%), elastase and total
      protein in exudates (by up to 80%), and local levels of cytokines (by up to 90%).
      Each of these parameters was significantly more affected in A2AR-KO mice. CXCL1-3
      levels were largely unaffected. The effects of aging were not observed
      systemically. Preventing neutrophil influx into the air pouch caused a comparable
      cytokine pattern in young WT mice. Gene expression (mRNA) in leukocytes was
      affected, with CXCL1 and CCL4 increasing and with TNF and IL-1alpha
      decreasing.ConclusionAging has deleterious effects on the acute inflammatory
      response and neutrophil-related activities, and defective migration appears as an
      important factor. A functional A2AR signaling pathway delays some of these.

PMID- 29064821
TI  - Senescence-associated ultrastructural features of long-term cultures of induced
      pluripotent stem cells (iPSCs).
AB  - Induced pluripotent stem cells (iPSCs) hold great promise for developing
      personalized regenerative medicine, however characterization of their biological
      features is still incomplete. Moreover, changes occurring in long-term cultured
      iPSCs have been reported, suggesting these as a model of cellular aging. For this
      reason, we addressed the ultrastructural characterization of iPSCs, with a focus
      on possible time-dependent changes, involving specific cell compartments. To this
      aim, we comparatively analysed cultures at different timepoints, by an innovative
      electron microscopic technology (FIB/SEM). We observed progressive loss of cell
      to-cell contacts, associated with increased occurrence of exosomes. Mitochondria
      gradually increased, while acquiring an elongated shape, with well-developed
      cristae. Such mitochondrial maturation was accompanied by their turnover, as
      assessed by the presence of autophagomes (undetectable in young iPSCs), some
      containing recognizable mitochondria. This finding was especially frequent in
      middle-aged iPSCs, while being occasional in aged cells, suggesting early
      autophagic activation followed by a decreased efficiency of the process with
      culturing time. Accordingly, confocal microscopy showed age-dependent alterations
      to the expression and distribution of autophagic markers. Interestingly,
      responsivity to rapamycin, highest in young iPSCs, was almost lost in aged cells.
      Overall, our results strongly support long-term cultured iPSCs as a model for
      studying relevant aspects of cellular senescence, involving intercellular
      communication, energy metabolism, and autophagy.

PMID- 29064822
TI  - Advanced capabilities for materials modelling with Quantum ESPRESSO.
AB  - Quantum EXPRESSO is an integrated suite of open-source computer codes for quantum
      simulations of materials using state-of-the-art electronic-structure techniques,
      based on density-functional theory, density-functional perturbation theory, and
      many-body perturbation theory, within the plane-wave pseudopotential and
      projector-augmented-wave approaches. Quantum EXPRESSO owes its popularity to the
      wide variety of properties and processes it allows to simulate, to its
      performance on an increasingly broad array of hardware architectures, and to a
      community of researchers that rely on its capabilities as a core open-source
      development platform to implement their ideas. In this paper we describe recent
      extensions and improvements, covering new methodologies and property calculators,
      improved parallelization, code modularization, and extended interoperability both
      within the distribution and with external software.

PMID- 29064823
TI  - Graphene-vertically aligned carbon nanotube hybrid on PDMS as stretchable
      electrodes.
AB  - Stretchable electrodes are a critical component for flexible electronics such as
      displays, energy devices, and wearable sensors. Carbon nanotubes (CNTs) and
      graphene have been considered for flexible electrode applications, due to their
      mechanical strength, high carrier mobility, and excellent thermal conductivity.
      Vertically aligned carbon nanotubes (VACNTs) provide the possibility to serve as
      interconnects to graphene sheets as stretchable electrodes that could maintain
      high electrical conductivity under large tensile strain. In this work, a graphene
      oxide (GO)-VACNT hybrid on a PDMS substrate was demonstrated. Here, 50 MUm long
      VACNTs were grown on a Si/SiO2 wafer substrate via atmospheric pressure chemical
      vapor deposition. VACNTs were directly transferred by delamination from the
      Si/SiO2 to a semi-cured PDMS substrate, ensuring strong adhesion between VACNTs
      and PDMS upon full curing of the PDMS. GO ink was then printed on the surface of
      the VACNT carpet and thermally reduced to reduced graphene oxide (rGO). The sheet
      resistance of the rGO-VACNT hybrid was measured under uniaxial tensile strains up
      to 300% applied to the substrate. Under applied strain, the rGO-VACNT hybrid
      maintained a sheet resistant of 386 +/- 55 Omega/sq. Cyclic stretching of the rGO
      VACNT hybrid was performed with up to 50 cycles at 100% maximum tensile strain,
      showing no increase in sheet resistance. These results demonstrate promising
      performance of the rGO-VACNT hybrid for flexible electronics applications.

PMID- 29064820
TI  - Identification of polymorphisms in cancer patients that differentially affect
      survival with age.
AB  - The World Health Organization predicts that the proportion of the world's
      population over 60 will almost double from 12% to 22% between 2015 and 2050.
      Ageing is the biggest risk factor for cancer, which is a leading cause of deaths
      worldwide. Unfortunately, research describing how genetic variants affect cancer
      progression commonly neglects to account for the ageing process. Herein is the
      first systematic analysis that combines a large longitudinal data set with a
      targeted candidate gene approach to examine the effect of genetic variation on
      survival as a function of age in cancer patients. Survival was significantly
      decreased in individuals with heterozygote or rare homozygote (i.e. variant)
      genotypes compared to those with a common homozygote genotype (i.e. wild type)
      for two single nucleotide polymorphisms (rs11574358 and rs4147918), one gene
      (SIRT3) and one pathway (FoxO signalling) in an age-dependent manner. All
      identified genes and pathways have previously been associated with ageing and
      cancer. These observations demonstrate that there are ageing-related genetic
      elements that differentially affect mortality in cancer patients in an age
      dependent manner. Understanding the genetic determinants affecting prognosis
      differently with age will be invaluable to develop age-specific prognostic
      biomarkers and personalized therapies that may improve clinical outcomes for
      older individuals.

PMID- 29064824
TI  - Uncoupling VOR and vestibuloautonomic retention to Coriolis acceleration training
      in student pilots and control subjects.
AB  - PURPOSE: Explore the different vestibular physiologic response retention patterns
      after Coriolis acceleration training in student pilots and extend the results for
      use with Chinese astronauts in the future. METHODS: Twelve healthy control male
      subjects were screened from males familiar with vestibular training and who
      physically resembled the astronauts. Fourteen student pilots were selected from
      23 participants by rotational vestibular function tests. All subjects were
      exposed to five-day continuous or intermittent Coriolis acceleration training.
      Subjective motion sickness (MS) symptom scores, electrocardiography,
      electrogastrography (EGG), post-rotatory nystagmus and renin-angiotensin system
      responses were measured before, during and after rotational vestibular function
      tests at different times after vestibular training. RESULTS: Subjects could
      tolerate 10 min or 15 min of vestibular with mild MS symptoms. Retention of
      vestibular autonomic responses (retention of MS symptom scores, heart rate
      variability, power density of EGG, variations in levels of arginine vasopressin)
      were approximately 1 week for control subjects and approximately 5 weeks for
      student pilots. Decreases in slow-phase velocity of post-rotatory nystagmus were
      maintained for 14 weeks for control subjects and 9 weeks for student pilots.
      CONCLUSIONS: Retention of the vestibulo-autonomic reaction after vestibular
      training was different for control subjects and student pilots. All parameters
      related to autonomic responses could be maintained at low levels after vestibular
      training for approximately 1 week for control subjects and approximately 5 weeks
      for student pilots. Uncoupling patterns between post-rotatory nystagmus and the
      vestibulo-autonomic reaction may be helpful in the design of clinical
      rehabilitation plans for balance-disorder patients and for exploration of
      artificial gravity in future space missions.

PMID- 29064825
TI  - Development of a new software and test setup for analyzing hVOR in very young
      children by vHIT.
AB  - INTRODUCTION: Earlier work revealed that vHIT examination is often difficult to
      perform on very young children. In particular, the calibration of the system can
      be difficult, as active cooperation of the patient is required. Additionally, the
      patient must be able to follow the examiner's instructions, which is challenging
      for very young children. Therefore, the aim of the present study was to develop
      and validate a new, software-based approach enabling vHIT testing of young
      children and infants. METHODS AND MATERIALS: Six patients (3 boys and 3 girls)
      aged 5-36 months were included in a prospective, monocentric study between
      January 2015 and August 2015.The newly developed intuitive software enabled
      calibration of the eye position signal with the subjects fixating on animated
      animal graphics which were projected on a screen. Testing ten healthy adults
      validated this new calibration and measurement method. After calibration, a vHIT
      goggle (EyeSeeCam (c)) was used to perform head impulses in the horizontal plane
      while the patient was watching a movie sitting on their parent's lap or in a baby
      chair. At least 15 impulses to each side were obtained and the occurrence of
      refixation saccades was analyzed. All tests were performed by one of two
      experienced examiners. RESULTS: The new calibration method and modified test
      setup provided reproducible results for all patients tested. An increased
      incidence of artifacts was not observed. In 2 patients, more than one test was
      needed. None of the included children showed catch-up overt or catch-up covert
      saccades. There was no gain reduction of more than two standard deviations as
      compared to the normative results published in the literature on vHIT
      examinations of children. CONCLUSION: The proposed protocol allows vHIT testing
      in very young children and infants (aged 5 months to 3 years). The study
      emphasizes that vHIT is an easy and sensitive screening tool to evaluate
      vestibular function in children and should be used as the gold standard in
      pediatric vestibular assessment.

PMID- 29064826
TI  - EthovisionTM analysis of open field behaviour in rats following bilateral
      vestibular loss.
AB  - Bilateral vestibular loss (BVL) causes a unique behavioural syndrome in rodents,
      with symptoms such as locomotor hyperactivity and changes in exploratory
      behaviour. Many of these symptoms appear to be indirect consequences of the loss
      of vestibular reflex function and are difficult to explain. Although such
      symptoms have been reported before, there have been few systematic studies of the
      effects of BVL using automated digital tracking systems in which many behavioural
      symptoms can be measured simultaneously with high precision. In this study, data
      were obtained from rats with BVL induced by intratympanic sodium arsanilate
      injections (n = 7) or sham injections (n = 8) and their behaviour in the open
      field was measured at 3 days and 23 days post-injection using EthovisionTM
      tracking software. BVL rats demonstrated reduced thigmotaxis, with more time
      spent in the central zones. Twenty-three days post-injection, BVL animals showed
      increased locomotor activity in the open field. The increase in activity was also
      reflected in the number of transitions between each zone of the field. In
      addition to increased activity, BVL animals showed increased whole body rotations
      following lesions. Using linear discriminant analysis (LDA) and random forest
      classification (RFC), we were able to show that the indirect behavioural effects
      of BVL, excluding direct measurement of vestibular reflex function, could
      correctly predict whether animals had received a BVL with a high degree of
      accuracy at both day 3 and day 23 post-BVL (83% and 100% for LDA, and 100% and
      100% for RFC, respectively). RFC has been similarly successful in classifying
      other hyperactivity syndromes such as attention deficit hyperactivity disorder.
      These results suggest that BVL results in a unique behavioural signature that can
      identify vestibular loss in rats even without direct vestibular reflex
      measurements.

PMID- 29064827
TI  - Mental body transformation deficits in patients with chronic balance disorders.
AB  - BACKGROUND: Movements may be generated consistent with imagining one's own body
      transformed or "disembodied" to a new position. Based on this concept we
      hypothesized that patients with objective balance deficits (obj-BD) would have
      altered neural transformation processes executing own body transformation (OBT)
      with functional consequences on balance control. Also we examined whether feeling
      unstable due to dizziness only (DO), without an obj-BD, also lead to an impaired
      OBT. METHODS: 32 patients with chronic dizziness were tested: 16 patients with
      obj-BD as determined by balance control during a sequence of stance and gait
      tasks, 16 patients with dizziness only (DO). Patients and 9 healthy controls
      (HCs) were asked to replicate roll trunk movements of an instructor in a life
      size video: first, with spontaneously copied (SPO) or "embodied" egocentric
      movements (lean when the instructor leans); second, with "disembodied" or
      "transformed" movements (OBT) with exact replication - lean left when the
      instructor leans left. Onset latency of trunk roll, rise time to peak roll angle
      (interval), roll velocity, and amplitude were measured. RESULTS: SPO movements
      were always mirror-imaged. OBT task latencies were significantly longer and
      intervals shorter than for SPO tasks (p < 0.03) for all groups. Obj-BD but not DO
      patients had more errors for the OBT task and, compared to HCs, had longer onset
      latencies (p < 0.05) and smaller velocities (p < 0.003) and amplitudes (p <
      0.001) in both the SPO and OBT tasks. Measures of DO patients were not
      significantly different from those of HCs. CONCLUSIONS: Mental transformation
      (OBT) and SPO copying abilities are impaired in subjects with obj-BD and
      dizziness, but not with dizziness only. We conclude that processing the
      neuropsychological representation of the human body (body schema) slows when
      balance control is deficient.

PMID- 29064828
TI  - Differences in head impulse test results due to analysis techniques.
AB  - BACKGROUND: Different analysis techniques are used to define vestibulo-ocular
      reflex (VOR) gain between eye and head angular velocity during the video head
      impulse test (vHIT). Comparisons would aid selection of gain techniques best
      related to head impulse characteristics and promote standardisation. OBJECTIVE:
      Compare and contrast known methods of calculating vHIT VOR gain. METHODS: We
      examined lateral canal vHIT responses recorded from 20 patients twice within 13
      weeks of acute unilateral peripheral vestibular deficit onset. Ten patients were
      tested with an ICS Impulse system (GN Otometrics) and 10 with an EyeSeeCam (ESC)
      system (Interacoustics). Mean gain and variance were computed with area, average
      sample gain, and regression techniques over specific head angular velocity (HV)
      and acceleration (HA) intervals. RESULTS: Results for the same gain technique
      were not different between measurement systems. Area and average sample gain
      yielded equally lower variances than regression techniques. Gains computed over
      the whole impulse duration were larger than those computed for increasing HV.
      Gain over decreasing HV was associated with larger variances. Gains computed
      around peak HV were smaller than those computed around peak HA. The median gain
      over 50-70 ms was not different from gain around peak HV. However, depending on
      technique used, the gain over increasing HV was different from gain around peak
      HA. Conversion equations between gains obtained with standard ICS and ESC methods
      were computed. For low gains, the conversion was dominated by a constant that
      needed to be added to ESC gains to equal ICS gains. CONCLUSIONS: We recommend
      manufacturers standardize vHIT gain calculations using 2 techniques: area gain
      around peak HA and peak HV.

PMID- 29064829
TI  - Cervical kinematics in patients with vestibular pathology vs. patients with neck
      pain: A pilot study.
AB  - OBJECTIVE: Research has consistently shown cervical kinematic impairments in
      subjects with persistent neck pain (NP). It could be reasoned that those with
      vestibular pathology (VP) may also have altered kinematics since vestibular
      stimulation via head movement can cause dizziness and visual disturbances.
      However, this has not been examined to date. This pilot study investigated
      changes in cervical kinematics between asymptomatic control, NP and VP subjects
      using a Virtual Reality (VR) system. It was hypothesised that there would be
      altered kinematics in VP subjects, which might be associated with dizziness and
      visual symptoms. DESIGN: Pilot cross sectional observational study. PARTICIPANTS:
      Twenty control, 14 VP and 20 NP subjects. INTERVENTION: Not applicable. MAIN
      OUTCOME MEASURES: Measures included questionnaires (neck disability index, pain
      on movement, dizziness and pain intensity, visual disturbances) and cervical
      kinematics (range, peak and mean velocity, smoothness, symmetry, and accuracy of
      cervical motion) using a virtual reality system. RESULTS: Results revealed
      significantly decreased mean velocity and symmetry of motion in both planes in
      those with NP but no differences in accuracy or range of motion. No significant
      differences were seen between VP subjects and asymptomatic controls. However,
      correlation analysis showed some moderate correlations between dizziness to
      selected kinematics in both the NP and the VP groups. CONCLUSIONS: These results
      support that cervical kinematics are altered in NP patients, with velocity most
      affected. There is potential for VP subjects to also have altered kinematics,
      especially those who experience dizziness. More research is required.

PMID- 29064830
TI  - Evaluation of vascular variations at cerebellopontine angle by 3D T2WI magnetic
      resonance imaging in patients with vertigo.
AB  - BACKGROUND: Vascular loops of the anterior-inferior cerebellar artery (AICA) at
      the cerebellopontine angle (CPA) are considered related to auditory-vestibular
      symptoms. Clinical association of these anatomical aberrations, which can be
      grouped together as vascular compression syndromes, is controversial. Magnetic
      resonance imaging (MRI) is widely used to visualize this anatomical region, given
      its high sensitivity and specificity. OBJECTIVE: To elucidate the clinical
      relationship of vertigo symptoms with vascular loop compression syndrome by
      evaluating the neurovascular contacts of the vestibulocochlear nerve (VCN) and
      AICA at the CPA and internal auditory canal via high-resolution MRI. METHODS: The
      study included 417 patients (178 with vertigo and 239 without vertigo) undergoing
      MRI for various clinical causes. MRI scans were assessed to study the presence of
      vascular abnormalities at the CPA. RESULTS: According to our findings, type 1
      vascular variation was observed most frequently in both sides. MRI findings were
      similar for the patients with and without vertigo. CONCLUSIONS: Identifying the
      prevalence of the vascular loops of the AICA primarily depends on diagnostic
      technique, and our results identified a slightly higher prevalence than those of
      previous studies, which might be partly related to the high-sensitivity of 3
      dimensional T2-weighted MRI.

PMID- 29064831
TI  - Vestibular vertigo is associated with abnormal sleep duration.
AB  - BACKGROUND/OBJECTIVE: Several small studies in animals and humans have suggested
      a relationship between vestibular function and sleep. In this study, we evaluate
      the association between vestibular vertigo and sleep duration in a large,
      representative sample of US adults. METHODS: We used data from the National
      Health Interview Survey, which administered a Balance Supplement in 2008 in a
      sample of 20,950 adult respondents. We evaluated the cross-sectional association
      between vestibular vertigo (based on a well-validated definition) and sleep
      duration (defined as short <6 hours, normal 6-8 hours, and long >8 hours). We
      performed multiple and multinomial logistic regression analyses to estimate the
      odds ratio and relative risk ratio (RRR) of impaired sleep duration compared to
      normal sleep duration associated with vestibular vertigo. Analyses were adjusted
      for demographic, lifestyle and health behavior characteristics as well as
      relevant comorbid conditions. RESULTS: Thirty percent of individuals with
      vestibular vertigo reported abnormal sleep duration (15.5% short duration and
      14.8% long duration). In adjusted analyses, individuals with vestibular vertigo
      had a 1.75 (95% CI 1.45-2.11) RRR of having short sleep duration compared to
      individuals without vestibular vertigo, and a 1.55 (95% CI 1.26-1.91) RRR of
      having long sleep duration compared to individuals without vestibular vertigo.
      CONCLUSION: This study presents epidemiologic evidence to support the association
      between vestibular function and sleep duration. Individuals with vestibular
      vertigo had a higher RRR for abnormally short or long sleep duration. Further
      work is needed to evaluate the causal direction(s) of this association.

PMID- 29064833
TI  - Micro-RNAs in transplant tolerance.
AB  - PURPOSE OF REVIEW: Micro-RNAs (miRNAs) are highly conserved small RNA molecules
      that have selective gene-regulatory functions. This posttranscriptional
      regulation by miRNAs is critical for many immunological processes. Many
      developments in establishing the biological role of miRNAs in solid organ
      transplantation have been generated in the last decade. Discoveries of immune
      regulation by miRNAs, resulting in graft prolongation and transplant tolerance,
      are rapidly advancing and are the subject of this review. RECENT FINDINGS: Many
      elegant experimental studies have revealed intriguing associations between
      transplant tolerance and specific miRNA profiles. These findings have provided
      insight into the miRNAs critical for sustaining immune suppression, and have
      revealed common miRNA pathways that should be further investigated and/or
      targeted therapeutically. Further reports have strategized and corroborated
      different methods of manipulating miRNA expression for prolonging allograft
      survival, yielding promising preclinical evidence of the efficacy of miRNA-based
      therapies. SUMMARY: The review covers these recent developments in miRNA research
      that can revolutionize how we implement diagnostics and prognostics and how we
      can strategize transplantation therapies.

PMID- 29064832
TI  - Prototype tests of vertical and torsional alignment nulling for screening
      vestibular function.
AB  - BACKGROUND: We have developed a non-invasive, behavioral measure of ocular
      alignment using a computer tablet, colored lenses, and touch screen software.
      OBJECTIVE: The goal of this study was to determine if these tests differentiate
      healthy controls from patients with vestibular disorders. METHODS: In the
      vertical alignment nulling test (VAN), subjects were asked to adjust a horizontal
      line that was offset vertically from a fixed horizontal line. In the torsional
      alignment nulling test (TAN) subjects were asked to adjust a line that was
      rotationally offset (i.e. clockwise) from a fixed horizontal line. We measured
      VAN and TAN in 14 healthy controls and 8 patients with known vestibular
      disorders. RESULTS: Patients had significantly worse scores than controls on TAN,
      (mean 2.2 vs 0.75, p = 0.01), and no differences for scores compared to controls
      on VAN, (mean 0.4 vs 0.8, p = 0.07). CONCLUSIONS: These results suggest that TAN,
      and possibly VAN, have potential for identifying misalignments in ocular
      position. After further technical development these tests might be useful in the
      future for screening patients in facilities that are not equipped to perform
      cervical and ocular vestibular evoked myogenic potentials.

PMID- 29064835
TI  - Spine Registries: Where Do We Stand?
AB  - To curb the unsustainable rise in health care costs, novel payment models are
      being explored which focus on value rather than volume. Underlying this reform is
      an accurate understanding of costs and outcomes. The Patient Protection and
      Affordable Care Act, the Institute of Medicine, and the Agency for Healthcare
      Research and Quality have specifically advocated for the use of registries to
      help define the real-world effectiveness of surgical interventions to help guide
      health care reform. Registries can help define value by documenting surgical
      efficacy, and specifically by reporting patient-based outcome measures. Over the
      past 10 years, several spine registries have been initiated and some others have
      expanded. These are providing a repository of evidence for surgical value.
      Herein, we will review the components of a well-designed registry and provide
      examples of such registries and their impact on health care delivery.

PMID- 29064836
TI  - Beware of the force of the horse: mechanisms and severity of equestrian-related
      injuries.
AB  - BACKGROUND: Equestrian-related injuries (ERIs) are relatively severe compared
      with injuries in other popular sports. Previous studies on epidemiology of ERIs
      vary widely and mainly focus on incidence instead of severity of the injury.
      PURPOSE: The aim of this study was to determine incidence, mechanisms and
      severity of ERIs in two Dutch hospitals (level 1 and level 2 trauma centers) over
      a 5-year period. PATIENTS AND METHODS: All patients with ERIs who visited the
      emergency departments of VieCuri Medical Centre in Venlo and Maastricht
      University Medical Centre+ in Maastricht, The Netherlands, between July 2010 and
      June 2015 were retrospectively included. Clinical data were extracted from
      medical records. RESULTS: Most ERIs occurred in mounted riders (646 events; 68%);
      94.9% of which involved a fall. Being kicked (42.5%) or trapped (30.1%) was the
      most common cause of injury in unmounted riders. Most frequently injured body
      parts were the upper extremities (43.8%) in mounted riders and lower extremities
      (40.5%) in the unmounted group. A relatively high percentage of facial injuries
      (9.7%) were found in the unmounted group. Seventeen per cent of all ERIs required
      admission. The median Injury Severity Score was 5 in the admitted population and
      1 in the total population. CONCLUSION: Horseback riding is a risky activity.
      Prior studies particularly studied admitted patients in level 1 trauma centers
      outside of Europe and demonstrated a high risk of significant injury. However,
      our study demonstrates that these studies in selected groups might have
      overestimated the severity of ERIs in the general population.

PMID- 29064838
TI  - Study of the Effectiveness of Multipurpose Solutions on the Bacterial
      Disinfection of Silicone Hydrogel Contact Lenses In Vitro.
AB  - OBJECTIVES: To assess the antimicrobial effectiveness of multipurpose solutions
      in regard to the disinfection of silicone hydrogel contact lenses (CL) using a
      study of clinical bacterial isolates from ocular material. METHODS: Three
      multipurpose solutions (solution A: polyhexamethylene biguanide 0.00025 g/100 mL;
      solution B: polyquaternary-1 0.001% and myristamidopropyl dimethylamine 0.0006%;
      and solution C: polyaminopropyl biguanide 0.00013% and polyquaternary 0.0001%)
      were used as a 3-phase disinfection on silicone hydrogel CL contaminated with
      bacteria from clinical isolates that were divided into five groups (group 1:
      Pseudomonas aeruginosa; group 2: Staphylococcus aureus; group 3: Staphylococcus
      epidermidis; group 4: Streptococcus spp; and group 5: enterobacteria). RESULTS:
      No differences were observed between the 24- and 48-hr measurements in any of the
      samples, and the positivity of microorganisms in T0 was 100% for all solutions;
      it was 0% in T3. Therefore, only steps T1 (rubbing followed by rinsing) and T2
      (rubbing followed by rinsing and immersion of CL into solution) were considered
      for analysis at the 24-hr measurement time. Throughout the phases, a decrease in
      the number of bacteria was observed, culminating in the elimination (no recovery)
      of all microorganisms in the three solutions. CONCLUSIONS: At the end of the
      proposed process, the tested solutions were effective.

PMID- 29064837
TI  - Co-management of cataract and glaucoma in the era of minimally invasive glaucoma
      surgery.
AB  - PURPOSE OF REVIEW: This review discusses the options available to be used in
      conjunction with phacoemulsification cataract surgery to control intraocular
      pressure. We present a strategy for planning which surgery should be performed
      based on goals of care. RECENT FINDINGS: New clinical evidence for using the
      CyPass, Kahook and Xen45 devices has been published recently and is summarized.
      SUMMARY: Cataract and glaucoma frequently exist together. Because the field of
      glaucoma surgical care is expanding and cataract surgery is becoming
      progressively safer, it is important to frequently re-evaluate our treatment
      paradigms. We review and evaluate current studies and treatment options.

PMID- 29064839
TI  - Sex differences in the association between a previous cancer diagnosis and the
      use of medication.
AB  - We aimed to quantify the association between a previous cancer diagnosis and
      medication use, depicting possible sex differences. We analysed data from a
      representative sample of the Portuguese adult population (n=32 610), which was
      collected through face-to-face interviews, using a structured questionnaire. The
      effect of a previous diagnosis of cancer was quantified through prevalence ratios
      (PR), adjusted for age, education and region of residence. Cancer survivors (CS)
      reported higher use of prescribed medication, with greater adjusted PR among men
      (1.25 vs. 1.13, P for interaction=0.001). Compared with the general population,
      male CS reported higher use of drugs for sleep problems, allergies and
      antibiotics, whereas female CS reported greater consumption of drugs for
      depression, anxiety, sleep problems and pain. This study contributes towards
      understanding sex disparities in the impact of cancer survival on medication use.

PMID- 29064840
TI  - The assessment and management of defecatory dysfunction: a critical appraisal.
AB  - PURPOSE OF REVIEW: To summarize the advances in diagnostic modalities and
      management options for defecatory dysfunction and highlight the areas in need of
      further research. RECENT FINDINGS: The diagnostic utility of high-resolution
      anorectal manometry (ARM), which has emerged as a promising tool for the
      diagnosis of defecatory dysfunction, appears to be questionable in
      differentiating disease from normal physiology. There also seems to be
      discrepancy between results of various tests of anorectal function in the
      diagnosis of defecatory dysfunction. New revisions in diagnostic criteria for
      defecatory dysfunction by Rome IV consortium, may enhance its diagnostic yield.
      Biofeedback remains to be the most effective evidence-based treatment option for
      patients with defecatory dysfunction. Anorectal pressure profile cannot predict
      or mediate the success of biofeedback. Biofeedback may improve the symptoms
      through central effects. SUMMARY: Despite the advances in the ARM and
      defecography techniques, no one test has been able to be considered as the 'gold
      standard' for diagnosis of defecatory dysfunction. The mechanism of action of
      biofeedback in defecatory dysfunction remains poorly understood.

PMID- 29064842
TI  - Effect of varenicline on behavioral deficits in a rat model of Parkinson's
      disease induced by unilateral 6-hydroxydopamine lesion of substantia nigra.
AB  - Nicotinic acetylcholine receptors (nAChRs) are implicated in the pathogenesis of
      Parkinson's disease (PD). Varenicline tartrate is a partial agonist at
      alpha4beta2 and full agonist at alpha7 neuronal nAChR subunits. A unilateral
      lesion of the substantia nigra (SN) has been used as a reliable model of PD. This
      study aimed to investigate the effect of varenicline on locomotor and
      nonlocomotor behavioral deficits induced by a unilateral lesion of the SN induced
      by 6-hydroxydopamine (6-OHDA) (8 ug/4 ul). Varenicline (1 mg/kg) was administered
      to the lesioned rats daily for 2 weeks, which commenced 3 weeks after 6-OHDA
      administration. The results showed that varenicline improved motor deficits
      induced by 6-OHDA. It improved locomotor and nonlocomotor activities such as
      forelimb use, rotarod performance, and forelimb asymmetry. Varenicline did not
      change rearing or vibrissae-elicited forelimb placing but did increase
      apomorphine-induced rotation. In conclusion, the present results suggest that
      drugs with specific partial/full agonistic activity on nAChR subunits could be of
      value in the treatment of neurodegenerative disorders such as PD.

PMID- 29064841
TI  - The effect of nicotine pre-exposure on demand for cocaine and sucrose in male
      rats.
AB  - The aim of the present study was to determine how nicotine pre-exposure affects
      the elasticity of demand for intravenous cocaine and for sucrose pellets in adult
      male rats. In Experiment 1, demand for cocaine was assessed in rats that had
      nicotine in their drinking water. Nicotine pre-exposure significantly decreased
      rats' willingness to defend cocaine consumption as the price (measured as the
      number of responses per cocaine infusion) increased compared with a control group
      with no nicotine pre-exposure. That is, nicotine increased the elasticity of
      demand for cocaine infusions. Experiment 2 repeated the first experiment, but
      with rats working for sucrose pellets instead of cocaine. Nicotine pre-exposure
      had no effect on the elasticity of demand for sucrose. This pattern of results
      suggests that nicotine pre-exposure can reduce the reinforcing effects of
      cocaine, but not sucrose, in adult male rats.

PMID- 29064844
TI  - The Smurf transition: new insights on ageing from end-of-life studies in animal
      models.
AB  - PURPOSE OF REVIEW: Over the past 5 years, many articles were published concerning
      the prediction of high risk of mortality in apparently healthy adults, echoing
      the first description in 2011 of the Smurf phenotype, a harbinger of natural
      death in drosophila. RECENT FINDINGS: These recent findings suggest that the end
      of-life is molecularly and physiologically highly stereotyped, evolutionarily
      conserved and predictable. SUMMARY: Taken altogether, these results from
      independent teams using multiple organisms including humans draw the lines of
      future directions in ageing research. The ability to identify and study
      individuals about to die of natural causes with no apparent diseases is a game
      changer in this field. In addition, the public health applications are
      potentially of tremendous impact in our ageing societies and raise important
      ethical questions.

PMID- 29064843
TI  - Touchscreen technology in the study of cognition-related behavior.
AB  - There is a growing need for new translational animal models designed to capture
      complex behavioral phenotypes implicated in addiction and other neuropsychiatric
      conditions. For example, a complete understanding of the effects of commonly
      abused drugs, as well as candidate medications, requires assessments of their
      effects on learning, memory, attention, and other cognition-related behavior.
      Modern touch-sensitive technology provides an extremely flexible means to expose
      an experimental subject to a variety of complex behavioral tasks designed to
      assay dimensions of cognitive function before, during, and after drug
      administration. In addition to tailored variants of gold-standard cognitive
      assessments, touchscreen chambers offer the ability to develop novel tasks based
      upon the researcher's needs. This methods perspective presents (i) a brief review
      of previous touchscreen-based animal studies, (ii) a primer on the construction
      of a touch-sensitive experimental chamber, and (iii) data from a proof-of-concept
      study examining cross-species continuity in performance across a diverse
      assortment of animal subjects (rats, marmosets, squirrel monkeys, and rhesus
      macaques) using the repeated acquisition task - a modern variant of a traditional
      animal model of learning. Taken together, the procedures and data discussed in
      this review illustrate the point that contemporary touchscreen methodology can be
      tailored to desired experimental goals and adapted to provide formal similarity
      in cognition-related tasks across experimental species. Moreover, touchscreen
      methodology allows for the development of new translational models that emerge
      through laboratory and clinical discovery to capture important dimensions of
      complex behavior and cognitive function.

PMID- 29064845
TI  - Team Approach: Management of Postoperative Delirium in the Elderly Patient with
      Femoral-Neck Fracture.

PMID- 29064848
TI  - Decrease of trabecular bone score reflects severity of Crohn's disease: results
      of a case-control study.
AB  - OBJECTIVES: Osteoporosis and osteopaenia are known chronic complications of
      inflammatory bowel diseases. The trabecular bone score (TBS) provides an indirect
      measurement of bone microarchitecture, independent of bone mineral density (BMD).
      PATIENTS AND METHODS: The study was designed as a case-control study with the aim
      to assess and compare bone quantity and quality in patients with Crohn's disease
      (CD). We purposefully excluded postmenopausal women and patients on long-term
      corticosteroid therapy. RESULTS: The cohort consisted of 50 CD patients and 25
      healthy controls who matched in age, sex, weight, or vitamin D status. There was
      no significant difference between CD patients versus controls in the mean lumbar
      BMD of 0.982+/-0.119 versus 0.989+/-0.12 g/cm and the mean TBS score of 1.37+/
      0.12 versus 1.38+/-0.12. We observed significantly lower TBS, but not lumbar BMD,
      in CD patients with stricturing (B2, 1.36+/-0.08) or penetrating (B3, 1.32+/
      0.11) disease compared with those with luminal disease (B1, 1.42+/-0.11; P=0.003
      and <0.0001, respectively). We also observed lower mean+/-SD TBS in patients on
      versus not on anti-tumour necrosis factor-alpha therapy: 1.341+/-0.138 versus
      1.396+/-0.099, respectively. However, the difference between these groups failed
      to reach statistical significance (P=0.11). No similar finding was seen comparing
      lumbar BMD in these groups. CONCLUSION: For the first time, it was observed that
      TBS, but not BMD, correlates with the severity of CD. Our results therefore
      suggest that TBS can potentially help to identify high fracture risk CD patients
      better than BMD alone.

PMID- 29064847
TI  - Quality of life of hepatitis B virus surface antigen-positive patients with
      suppressed viral replication: comparison between inactive carriers and
      nucleot(s)ide analog-treated patients.
AB  - OBJECTIVE: Hepatitis B virus infection is a relevant health problem with more
      than 400 million infected people worldwide. Our aim was to analyze quality of
      life of hepatitis B virus surface antigen-positive patients in inactive status or
      treated with antivirals. PATIENTS AND METHODS: Patients referred to our center
      between February and October 2016 were prospectively enrolled. Half-structured
      interview was used for examining psychological symptoms and Illness Behavior
      Questionnaire for exploring attitudes toward illness. We used World Health
      Organization Quality of Life-short version survey for studying quality of life
      and logistic regression to find possible predictors of nonadequate quality of
      life. RESULTS: The study involved 102 patients. At Illness Behavior Questionnaire
      test, psychological perception of illness (21.6%), and denial of illness itself
      (13.7%) were the most frequent conditions. Inactive and treated subgroups were
      comparable for almost all variables and scores, but patients on treatment were
      significantly more often male, older, and cirrhotic. Sleep disturbance emerged as
      an independent predictor of inadequate quality of life in Physical health,
      anxiety in Social relationship, and both anxiety and hostility in Environmental
      health domain. CONCLUSION: Inactive carriers and patients on treatment showed the
      same global quality of life, but the second group was older and more frequently
      with an advanced liver disease. Further studies might specifically evaluate the
      impact of antiviral therapy on quality of life.

PMID- 29064850
TI  - The association between physical activity and the risk of symptomatic Barrett's
      oesophagus: a UK prospective cohort study.
AB  - BACKGROUND: Physical activity affects the functioning of the gastrointestinal
      system through both local and systemic effects and may play an important role in
      the aetiology of gastroesophageal reflux disease, Barrett's oesophagus and
      oesophageal adenocarcinoma. We investigated, for the first time in a large
      prospective cohort study, associations between recreational and occupational
      levels of physical activity and the incidence of Barrett's oesophagus.
      PARTICIPANTS AND METHODS: The European Prospective Investigation of Cancer
      Norfolk recruited 30 445 men and women between 1993 and 1997. Occupational and
      recreational levels of physical activity were measured using a baseline
      questionnaire. The cohort was followed up until 2015 to identify symptomatic
      cases of Barrett's oesophagus. Cox proportional hazard regression estimated
      hazard ratios (HR) for physical activity and the development of disease. RESULTS:
      Two hundred and three participants developed Barrett's oesophagus (mean age: 70.6
      years) the majority of whom were men (70.9%). There was an inverse association
      between standing occupations and disease risk [HR: 0.50, 95% confidence interval
      (CI): 0.31-0.82, P=0.006] when compared with sedentary jobs. Heavy manual
      occupations were positively associated with disease risk (HR: 1.66, 95% CI: 0.91
      3.00), but conventional statistical significance was not reached (P=0.09). No
      associations were found between recreational activity and the risk of Barrett's
      oesophagus (HR: 1.34, 95% CI: 0.72-2.50, P=0.35, highest vs. lowest levels of
      activity). CONCLUSION: Our study suggests that occupational levels of physical
      activity may be associated with the risk Barrett's oesophagus. However, further
      work is required to confirm and describe specific occupations that may be
      protective.

PMID- 29064849
TI  - The outcome of transanal endoscopic microsurgery in obese patients.
AB  - BACKGROUND: The prevalence of obesity is as high as one-third of the adult
      population in the ultrasound. Obese patients operated for rectal cancer are less
      likely to undergo sphincter-preserving surgery, and have an increased morbidity
      and mortality. We aim to report the outcomes of transanal-endoscopic-microsurgery
      (TEM) in obese patients with benign and malignant neoplasms. MATERIALS AND
      METHODS: An analysis was carried out of all patients undergoing TEM at a single
      institution between 2004 and 2015. Clinical, demographic, and pathologic data
      were analyzed in respect to BMI; a dichotomous variable was created categorizing
      the patients in this retrospective case series as either obese (BMI>=30) or
      nonobese (BMI<30). RESULTS: Of the 158 patients who underwent TEM during the
      study period, 51 (32%) were obese and 107 (68%) were nonobese. No significant
      differences were found in terms of patients' demographics and tumor
      characteristics. There were no significant differences in operative time [105 min
      (range: 75-170) and 98 (range: 56-170), respectively, P=0.2], hospital length of
      stay [3 days (range: 2-6) and 4 (range: 2-12), respectively, P=0.48], or
      complication rates (20 and 23%, respectively, P=0.68). CONCLUSION: TEM is a safe
      procedure for rectal neoplasms in the obese population. We found no difference in
      surgical time and completeness of specimen resection, and no increase in
      complications or length of stay in the hospital in obese versus nonobese
      patients. As for selected high risk patients, the TEM may be of benefit in obese
      patients with T1/T2N0M0 rectal cancer.

PMID- 29064851
TI  - De-novo versus recurrent hepatocellular carcinoma following direct-acting
      antiviral therapy for hepatitis C virus.
AB  - INTRODUCTION: A recent appearance of direct-acting antivirals (DAAs) led to a
      surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of
      treated patients have cirrhosis with a retained possibility to develop
      hepatocellular carcinoma (HCC) even after complete cure. We aimed to study
      tumoral differences between patients who developed HCC after DAAs as either a
      recurrence or de-novo HCC. METHODS: We retrospectively analyzed 89 patients who
      presented to our HCC multidisciplinary clinic with HCC lesions following DAA
      therapy. A total of 45 patients had complete response to HCC according to the
      modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another
      44 patients developed de-novo lesions after DAA treatment. Both groups were
      compared regarding their baseline characteristics, tumor criteria, response to
      DAAs as well response to HCC treatment. RESULTS: Both groups showed no
      significant difference regarding their baseline characteristics (age, sex, Child
      Pugh score, and performance status) or response to DAAs (P=0.5). No significant
      difference was present between groups according to number, site, and size of
      lesions. However, time elapsed between the end of DAAs therapy and first
      diagnosis of HCC was significantly longer in de-novo group (15.22+/-16.39 months)
      versus recurrence group (6.76+/-5.1 months) (P=0.008). In addition, response to
      ablation was significantly better in de-novo lesions compared with recurrent HCC
      (P=0.03). CONCLUSIONS: Although de-novo HCC lesions significantly developed later
      than recurrent lesions in DAAs-treated patients, their response rates were
      significantly better. No differences were detected between both groups in their
      response to DAAs and their tumoral characteristics.

PMID- 29064852
TI  - Association between insulin therapy and risk of liver cancer among diabetics: a
      meta-analysis of epidemiological studies.
AB  - As the results of the association between insulin therapy and risk of liver
      cancer among diabetics have been inconsistent in epidemiological studies, we
      conducted a meta-analysis to quantify this issue. Data of relevant
      epidemiological studies were collected by searching articles in PubMed, Web of
      Science, and Embase till 29 June 2017. Random-effects models were employed to
      combine study-specific risks. Five cohort studies and nine case-control studies
      were included in our meta-analysis with 285 008 patients with diabetes mellitus
      and 4329 liver cancer cases. When we compared insulin-use group with noninsulin
      use group in patients with diabetes mellitus, we observed a statistically
      significant association between insulin therapy and liver cancer, with an overall
      relative risk of 1.90 (95% confidence interval: 1.44-2.50, I=76.1%). We did not
      find heterogeneity between subgroups stratified by study characteristics and
      adjusted confounders, except for subgroups related to 'follow-up years' of cohort
      studies. The combined estimate was robust across sensitivity analysis, and no
      publication bias was detected. Our results indicated that insulin therapy was
      associated with elevated incidence of liver cancer among diabetics. Given the
      high prevalence of diabetes, avoiding excess or unnecessary insulin use to
      control the blood glucose may offer a potential public health benefit in reducing
      liver cancer risk. Further studies are warranted to investigate the types, doses,
      and treatment duration of insulin use in large sample size or cohort of diabetic
      patients.

PMID- 29064853
TI  - Red blood cell distribution width independently predicts 1-month mortality in
      acute decompensation of cirrhotic patients admitted to emergency department.
AB  - AIM: The aim of this study was to explore whether red blood cell distribution
      width (RDW) can help predict the risk of short-term mortality in patients with
      acute decompensation of cirrhosis. PATIENTS AND METHODS: We carried out a
      retrospective analysis of all patients consecutively admitted to the emergency
      department (ED) of the University Hospital of Verona (Italy) for acute
      decompensation of liver cirrhosis, between 1 June 2013 and 31 December 2016. The
      RDW value was measured at ED admission, along with collection of clinical
      features and other laboratory data, and was then correlated with severity of
      disease (Chronic Liver Failure Consortium Acute Decompensation score; CLIF-C AD
      score) and 1-month mortality. RESULTS: The final study population consisted of
      542 patients, 80 (14.8%) of whom died within 30 days after ED admission. The
      median RDW of patients who died was significantly higher than the median RDW of
      those who survived (17.4 vs. 15.5%; P<0.001). The percentage of patients who died
      significantly increased across different RDW quartiles (6.8, 9.7, 11.5 and 32.1%,
      P<0.001). In univariate analysis, significant correlation was observed between
      RDW and clinical severity of acute decompensate cirrhosis (Child-Pugh score:
      r=0.198, P<0.001; Model for End-Stage Liver Disease score: r=0.311, P=0.001; CLIF
      C AD: 0.127, P=0.005). The combination of RDW and CLIF-C AD score exhibited
      better performance for predicting 1-month mortality than the CLIF-C AD score
      alone (area under the curve=0.769 vs. 0.720; P=0.006). In multivariate analysis,
      RDW was independently associated with a 1.2-2.3 higher risk of 1-month mortality.
      CONCLUSION: The assessment of RDW at ED admission may improve risk stratification
      of patients with acute decompensation of cirrhosis.

PMID- 29064854
TI  - CLINICAL COURSE OF INFLAMMATORY CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH
      FOCAL CHOROIDAL EXCAVATION.
AB  - PURPOSE: To report the clinical course of focal choroidal excavation associated
      with choroidal neovascularization in a case of choroidal inflammation. METHODS:
      Case report. RESULTS: A 41-year-old man presented with blurred vision and
      metamorphopsia in his left eye. Multimodal imaging including optical coherence
      tomography angiography showed nonconforming focal choroidal excavation in the
      setting of choroidal inflammation and the presence of choroidal
      neovascularization at the border of the excavation, nicely visualized by optical
      coherence tomography angiography. Pattern alteration from nonconforming to
      conforming focal choroidal excavation and choroidal neovascularization involution
      were observed after treatment with oral steroids. CONCLUSION: Multimodal imaging,
      including optical coherence tomography angiography, allowed to detect and monitor
      pattern focal choroidal excavation transformation and choroidal
      neovascularization reduction after treatment with oral steroids.

PMID- 29064855
TI  - ABNORMAL QUIESCENT NEOVASCULARIZATION IN A PATIENT WITH LARGE COLLOID DRUSEN
      VISUALIZED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
AB  - PURPOSE: We report a case of large colloid drusen complicated by extensive
      quiescent choroidal neovascularization in both eyes. METHODS: Case report.
      RESULTS: A 46-year old woman was referred to our department with diagnosis of
      early-onset retinal drusen. Review of examinations performed 16 years before
      along with current multimodal imaging evaluation showed the presence of numerous
      large colloid drusen, subsequently replaced by quiescent choroidal
      neovascularization in both eyes, nicely visualized by optical coherence
      tomography angiography. CONCLUSION: This case suggests progressive development of
      quiescent neovascularization beneath the drusen as a possible late evolution of
      degenerating large colloid drusens.

PMID- 29064856
TI  - Bone Mass Development from Childhood into Young Adulthood in Patients with
      Childhood-onset Inflammatory Bowel Disease.
AB  - BACKGROUND: Children who have inflammatory bowel disease (IBD) have increased
      risk of low bone mineral density (BMD). There is a scarcity of information on BMD
      development through puberty and into young adulthood in patients with childhood
      onset IBD. METHODS: We conducted a prospective longitudinal study of BMD in
      patients with childhood-onset IBD. In total, 74 children with IBD were followed
      into young adulthood, with a mean follow-up of 8.4 years. The BMD was assessed
      longitudinally using dual-energy X-ray absorptiometry of the lumbar spine, total
      hip and whole body, and related to anthropometric measures. RESULTS: Young adult
      male patients with IBD had lower mean BMD Z-scores for the lumbar spine at -0.8
      (+/-1.1 SD) and total hip at -0.5 (+/-0.9 SD), as compared to standard
      references. In young female patients, the BMD Z-scores were within the normal
      range at all 3 measured sites as compared to the standard references. There were
      no significant differences in the BMD Z-scores between patients with Crohn's
      disease and patients with ulcerative colitis. The female and male patients showed
      significantly improved mean lumbar spine BMD Z-scores during follow-up into young
      adulthood, indicating that bone accumulation in the lumbar spine continues beyond
      the expected age for achieving peak bone mass. CONCLUSIONS: Male patients with
      childhood-onset IBD seem to have an increased risk of compromised BMD in young
      adulthood. Both female and male patients with IBD seem to increase their BMD
      beyond the age for expected peak bone mass (see Video abstract, Supplemental
      Digital Content 1, http://links.lww.com/IBD/B648).

PMID- 29064858
TI  - Sheryl A Kingsberg, PhD 2017-2018 NAMS President.

PMID- 29064857
TI  - In Vivo Evaluation of Dual Acid-Etched and Grit-Blasted/Acid-Etched Implants With
      Identical Macrogeometry in High-Density Bone.
AB  - PURPOSE: Based on the current evidence, the effect of implant macrogeometry has a
      significant influence on osseointegration. Thus, this study evaluated
      histomorphometrically and histologically the bone response to acid-etched in
      comparison to grit-blasted/acid-etched (GB) and machined control (C) surfaced
      implants possessing identical macrogeometry placed in high-density bone.
      MATERIALS AND METHODS: Implant surface topography of the 3 different surfaced
      implants has previously been characterized. The macrogeometry of the implants
      were conical, and healing chambers were created in the cortical regions. The 3
      groups were placed in the external mandibular body of adult male sheep (n = 5).
      After 6 weeks in vivo, all samples were retrieved for histologic observation and
      histomorphometry (eg, bone-to-implant contact [BIC] and bone area fraction
      occupancy [BAFO]). RESULTS: No statistical difference was observed for BIC and
      for BAFO, although there was a tendency that the mean values for BAFO was higher
      for the textured surface groups. CONCLUSIONS: It is suggested that the effect of
      surface topography is minimal in high-density bone and osseointegration seemed to
      be macrogeometry dependent.

PMID- 29064859
TI  - Increasing the Accessibility of Sexual Assault Forensic Examinations: Evaluation
      of Texas Law SB 1191.
AB  - INTRODUCTION: Texas SB 1191 was enacted in 2013 with the intent of increasing
      access to medical forensic examinations for sexual assault victims by requiring
      every hospital with an emergency department to be prepared to provide a medical
      forensic examination if requested by a sexual assault victim. To realize that
      goal, the law also required basic forensic training for medical professionals
      before conducting a medical forensic examination as well as a requirement that
      hospitals develop a "plan to train personnel on sexual assault forensic evidence
      collection." METHODS: Interviews were conducted in 18 healthcare facilities (five
      with sexual assault nurse examiner [SANE] programs and 13 without SANE programs)
      in Dallas, Lubbock, and Austin to determine their awareness and compliance with
      SB 1191. RESULTS: The data suggest that the law had a little effect on actual
      practice, and sexual assault survivors still sought a SANE program for a medical
      forensic examination. DISCUSSION: Although SB 1191 is an important state level
      effort to make forensic examinations more readily available, it did not fully
      account for the challenges faced by smaller hospitals that do not see enough
      sexual assault victims to justify training staff to SANE standards and did not
      adequately address the training required by medical professionals to feel
      prepared to conduct a medical forensic examination.

PMID- 29064860
TI  - Global Voyeurism or Sustainable Ethical Practice?
AB  - This is a conceptual article exploring global voyeurism and service, overlaying
      ethical considerations in service within the profession of forensic nursing. Key
      elements considered include examining and reflecting on personal motivations,
      benefits, and consequences of service when viewed through an ethical perspective.
      Through this article we seek to examine the relationships between poverty tourism
      and service, while better supporting individual forensic nurses in their quest to
      align their actions with the ethical and practice comportment standards within
      the profession of nursing service globally. We include definition of terms,
      including professional identity, ethics and social justice, poverty tourism and
      voyeurism, global and professional service, cultural humility, partnerships, and
      trusting relationships. We conclude with implications, and considerations for
      forensic nursing.

PMID- 29064862
TI  - Stemless Prosthesis for Total Shoulder Arthroplasty.
AB  - The fourth generation of humeral components currently are being used in anatomic
      shoulder arthroplasty. Anatomic shoulder arthroplasty implants have evolved to
      better re-create anatomy, improve fixation, preserve bone, and facilitate
      revision surgery. Most of the design changes for shoulder arthroplasty implants
      have centered on the humeral stem, with a transition to shorter, metaphyseal
      humeral stems. Many of these humeral component design changes may be beneficial;
      however, long-term studies are necessary to determine if the results of anatomic
      shoulder arthroplasty with the use of newer humeral components can match those of
      anatomic shoulder arthroplasty with the use of older humeral components.

PMID- 29064863
TI  - The Influence of Collaboration: Ralph Waters' Friendship With John Lundy and the
      Spread of Regional Anesthesia.
AB  - Ralph Waters, the founder of the anesthesiology department and residency program
      at the University of Wisconsin-Madison, and John Lundy, the chair at the Mayo
      Clinic beginning in 1924, collaborated to expand regional anesthetic techniques
      and knowledge not only at their institutions, but also at institutions around the
      country through correspondence, meetings, and hosting of other anesthesiologists.
      The Ralph Waters Collection at the University of Wisconsin Archives was searched
      for information on Waters' and Lundy's involvement in regional anesthesia. This
      included publications by Waters and other anesthesiology department faculty, as
      well as personal correspondence with other leaders in anesthesia at that time.
      Correspondence between Waters and Lundy from this collection was reviewed in
      detail. This article underscores the importance of exchange of ideas by
      physicians through didactics, organizations, and research through the story of
      Ralph Waters and John Lundy's mutual exchange of ideas and even friendship
      beginning in the 1920s.

PMID- 29064864
TI  - Physiotherapist-Led Physical Activity Interventions Are Efficacious at Increasing
      Physical Activity Levels: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Physical activity (PA) interventions to address noncommunicable
      disease (NCD) risk are commonly delivered in private practice and outpatient
      physiotherapy settings. This study reviewed the efficacy of physiotherapist-led
      physical activity (PLPA) interventions at improving PA levels. DATA SOURCES:
      Twelve databases were searched using terms related to both physiotherapy and PA.
      English-language studies of all designs in adults were included. Meta-analyses
      were conducted separately for interventions measuring the following: (1)
      participants meeting recommended PA levels; (2) total PA at short- and long-term
      follow-up; and (3) total PA achieved after short and long PLPA interventions.
      Pooled effects were calculated using a fixed-effects model as standardized mean
      differences (SMDs). Nonstatistical analysis was used to identify the effect of
      PLPA interventions on the volume of PA performed at different intensities. MAIN
      RESULTS: From an initial 4140 studies, 8 were retained, and risk of bias ranged
      from low to high. Meta-analysis showed the odds of adults meeting minimum
      recommended PA levels were doubled in groups provided a PLPA intervention [OR =
      2.15, 95% confidence interval (CI) = 1.35-3.43]. Total PA levels were increased
      in the short term (SMD = 0.15, 95% CI = 0.03-0.27) but not in the long term.
      Longer term interventions did not improve outcomes. Nonstatistical analysis
      identified that PLPA interventions were efficacious at increasing the amount of
      PA adults performed at all intensities. CONCLUSIONS: Clinic-based PLPA
      interventions delivered in private practice, primary care, and outpatient
      settings were efficacious at increasing PA in adults at risk of NCDs.
      Improvements did not last long term and were not enhanced with longer
      interventions.

PMID- 29064865
TI  - Head Impact Exposure in Youth Soccer and Variation by Age and Sex.
AB  - OBJECTIVE: To examine variation in head impact exposure (HIE) by age and sex in
      youth soccer. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Youth
      soccer athletes (11-14 years old) in local clubs. EXPOSURES: Age and sex. OUTCOME
      MEASURES: Head impact exposure measured using adhesive-mounted accelerometers
      during 1 month of soccer. RESULTS: Forty-six youth athletes (54% female)
      participated. No athlete reported a concussion during the study. More males than
      females had at least 1 head impact >=15 g (P = 0.02). Of those who sustained a
      head impact above the 15-g threshold (57%), females sustained HIE of greater
      magnitude than males (median 47.4 g vs 33.3 g, P = 0.04). Eighty-five percent of
      athletes on U14 teams had at least 1 head impact >=15 g compared with 15% of
      athletes on U12 teams (P < 0.001). Poisson regression stratified by sex and
      controlling for team-suggested age effects were significant only for females (P =
      0.02). There was significant variation in HIE by team. There were no decrements
      in concussion symptoms, health-related quality of life, or neuropsychological
      testing after 1 month of soccer play. CONCLUSIONS: There is significant variation
      in HIE in youth soccer, which seems to be influenced by age and sex. Further
      studies are needed to better understand potential significance for injury
      prevention.

PMID- 29064866
TI  - "Recognize and Remove": A Universal Principle for the Management of Sports
      Injuries.
AB  - OBJECTIVE: To identify the locations and types of injury that result in players
      not being immediately removed from the field of play when injured and to quantify
      the magnitude of the situation. DESIGN: Prospective cohort epidemiological study
      with definitions and procedures compliant with the international consensus
      statement for studies in rugby. SETTING: Sevens World Series (SWS) (2008-2016)
      and Rugby World Cup (RWC) (2007, 2011, 2015). PARTICIPANTS: Players from 17
      countries taking part in the SWS and 22 countries taking part in the RWC. MAIN
      OUTCOME MEASURES: Location, type, and mean severity of injury, period of match
      when the injury occurred and whether players were removed from the field of play
      when injured. RESULTS: Injured players (51.5%) in the SWS and 33.1% of injured
      players in the RWC were immediately removed from the field of play at the time of
      injury. The percentages of players immediately removed varied from 16.7% for hand
      fractures (severity: 71 days) to 96.7% for shoulder dislocations/subluxations
      (severity: 105 days) during the SWS and from 4.5% for shoulder ligament sprains
      (severity: 25 days) to 65.9% for concussions (severity: 9 days) during the RWC.
      The percentage of players immediately removed from play when injured was not
      related to the severity of the injury sustained. CONCLUSIONS: A high proportion
      of players continue to play (in the same game) after sustaining an injury
      although the likelihood of being removed from play is not dependent on injury
      severity.

PMID- 29064867
TI  - Why Professional Football Players Chose Not to Reveal Their Concussion Symptoms
      During a Practice or Game.
AB  - OBJECTIVE: To determine why professional football players in Canada decided not
      to seek medical attention during a game or practice when they believed they had
      suffered a concussion. DESIGN: Retrospective survey. SETTING: Preseason Canadian
      Football League training camps. PARTICIPANTS: Four hundred fifty-four male
      professional football players. MAIN OUTCOME MEASURES: Reasons athletes did not
      seek medical attention for a presumed concussion during the previous season, how
      often this occurred and how important these reasons were in the decision process.
      RESULTS: One hundred six of the 454 respondents (23.4%) believed they had
      suffered a concussion during their previous football season and 87 of the 106
      (82.1%) did not seek medical attention for a concussion at least once during that
      season. The response "Did not feel the concussion was serious/severe and felt you
      could still continue to play with little danger to yourself" was the most
      commonly listed reason (49/106) for not seeking medical attention for a presumed
      concussion. Many players answered that they did not seek medical attention
      because they did not want to be removed from a game (42/106) and/or they did not
      want to risk missing future games (41/106) by being diagnosed with a concussion.
      CONCLUSIONS: Some professional football players who believed they had suffered a
      concussion chose not to seek medical attention at the time of injury. Players
      seemed educated about the concussion evaluation process and possible treatment
      guidelines, but this knowledge did not necessarily translate into safe and
      appropriate behavior at the time of injury.

PMID- 29064868
TI  - Association Between Previous Injury and Risk Factors for Future Injury in
      Preprofessional Ballet and Contemporary Dancers.
AB  - OBJECTIVES: To determine the prevalence of self-reported 1-year injury history
      and examine its association with preparticipation evaluation components aimed at
      predicting future injury risk (PPE-IP) among preprofessional ballet and
      contemporary dancers. DESIGN: Cross-sectional study. SETTING: Preprofessional
      ballet school, university contemporary dance program. PARTICIPANTS: Full-time
      preprofessional ballet and contemporary dancers. ASSESSMENT OF RISK FACTORS:
      Preparticipation evaluation consisted of the Athletic Coping Skills Inventory-28,
      body mass index, total bone mineral density, ankle range of motion, active
      standing turnout, lumbopelvic control, unipedal dynamic balance, and Y-Balance
      test. MAIN OUTCOME MEASURE: Self-reported 1-year history of dance-related medical
      attention and/or time-loss injury. RESULTS: A total of 155 ballet [n = 90, 80
      females, median age 15 years (range 11-19)] and contemporary [n = 65, 63 females,
      median age 20 years (range 17-30)] dancers participated. Forty-six percent (95%
      confidence interval (CI), 38.4-54.6) reported a 1-year injury history. Self
      reported injury history was not associated with any PPE-IP, however, an influence
      of age and psychological coping skills on the relationship between 1-year injury
      history and PPE-IP was identified. Multivariable analyses revealed that
      prevalence of 1-year injury history did not differ by age [referent group <15
      years; 15-18 years: odds ratio (OR) 0.80 (95% CI, 0.35-1.79); >18 years: OR 0.69
      (95% CI, 0.30-1.56)], or level of psychological coping skills [OR 1.35 (95% CI,
      0.61-2.94)]. CONCLUSIONS: The prevalence of self-reported 1-year injury history
      among preprofessional ballet and contemporary dancers is high. Although measures
      of PPE-IP did not differ based on injury history, it is important that age and
      psychological coping skills are considered in future dance injury prevention and
      prediction research. LEVEL OF EVIDENCE: Level 3 evidence.

PMID- 29064869
TI  - Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery
      in Children.
AB  - OBJECTIVE: Up to one-third of children with concussion have prolonged symptoms
      lasting beyond 4 weeks. Vision and vestibular dysfunction is common after
      concussion. It is unknown whether such dysfunction predicts prolonged recovery.
      We sought to determine which vision or vestibular problems predict prolonged
      recovery in children. DESIGN: A retrospective cohort of pediatric patients with
      concussion. SETTING: A subspecialty pediatric concussion program. PATIENTS (OR
      PARTICIPANTS): Four hundred thirty-two patient records were abstracted.
      ASSESSMENT OF RISK FACTORS: Presence of vision or vestibular dysfunction upon
      presentation to the subspecialty concussion program. MAIN OUTCOME MEASURES: The
      main outcome of interest was time to clinical recovery, defined by discharge from
      clinical follow-up, including resolution of acute symptoms, resumption of normal
      physical and cognitive activity, and normalization of physical examination
      findings to functional levels. RESULTS: Study subjects were 5 to 18 years (median
      = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular
      problems. A history of motion sickness was associated with vestibular
      dysfunction. Younger age, public insurance, and presence of headache were
      associated with later presentation for subspecialty concussion care. Vision and
      vestibular problems were associated within distinct clusters. Provocable symptoms
      with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and
      accommodative amplitude (AA) predicted prolonged recovery time. CONCLUSIONS:
      Vision and vestibular problems predict prolonged concussion recovery in children.
      A history of motion sickness may be an important premorbid factor. Public
      insurance status may represent problems with disparities in access to concussion
      care. Vision assessments in concussion must include smooth pursuits, saccades,
      near point of convergence (NPC), and accommodative amplitude (AA). A
      comprehensive, multidomain assessment is essential to predict prolonged recovery
      time and enable active intervention with specific school accommodations and
      targeted rehabilitation.

PMID- 29064870
TI  - Biomechanical Evaluation of Pediatric Anterior Cruciate Ligament (ACL)
      Reconstruction Techniques With and Without the Anterolateral Ligament (ALL).
AB  - BACKGROUND: Two popular physeal-sparing procedures used in the management of
      anterior cruciate ligament (ACL) injuries in skeletally immature patients are the
      iliotibial band (ITB) ACL reconstruction (ACLR) and the all-epiphyseal (AE) ACLR.
      Although there has been concern for overconstraint of the lateral compartment of
      the knee with the ITB ACLR technique, rotational stability, as provided by the
      anterolateral ligament (ALL) and ACL, has not been assessed in the setting of
      pediatric ACLR techniques. Our hypothesis is that the ITB ACLR and AE ACLR with
      ALL reconstruction (ALLR) will best replicate the biomechanical profile of the
      intact ACL that is lost with transection of the ACL and ALL. METHODS: Eight
      cadaveric legs were statically loaded with an anterior drawer force and varus,
      valgus, internal and external rotational moments at 0, 30, 60, and 90 degrees of
      flexion. Displacement and rotation were recorded in the following conditions:
      intact ACL/intact ALL, ACL-deficient/intact ALL, ITB ACLR/intact ALL, ITB
      ACLR/ALL-deficient, ACL-deficient/ALL-deficient, AE ACLR/ALL-deficient, AE
      ACLR/ALLR. RESULTS: Both ACLR techniques reduced anterior tibial translation from
      the ACL-deficient state, but neither restored it to the intact state (P<0.05),
      except in full extension. ALL deficiency increased anterior tibial translation in
      the ACL-deficient state (P<0.05). In rotational testing, no significant increase
      was seen with transection of the ACL, but the ACL-deficient/ALL-deficient state
      had a significant increase in internal rotation (P<0.05). This was significantly
      restored to the intact state at most flexion angles with the ITB ACLR without
      rotational overconstraint of the lateral compartment. The AE ACLR/ALL-deficient
      state and AE ACLR/ALLR improved rotational stability at lower flexion angles, but
      not at 60 and 90 degrees. There were no significant changes in varus/valgus
      moments. CONCLUSIONS: In this model, the ITB ACLR provided the superior
      biomechanical profile between our tested reconstructions. It best corrected both
      AP and rotatory stability without overconstraining the knee. The AE ACLR and AE
      ACLR/ALLR improved both parameters but not at all flexion angles and not as
      robustly. ACL deficiency in the knee increased anterior tibial translation, but
      did not affect rotatory stability. ALL deficiency in the knee increased anterior
      displacement and rotational moments in the ACL-deficient state. CLINICAL
      RELEVANCE: Cadaveric Laboratory Study. The ITB ACLR seems to be the
      biomechanically superior pediatric ACLR technique to regain translational and
      rotational stability.

PMID- 29064871
TI  - Best Practice Guidelines for Surgical Site Infection Prevention With Surgical
      Treatment of Early Onset Scoliosis.
AB  - BACKGROUND: Postoperative surgical site infection (SSI) is unfortunately a
      commonly encountered complication in the surgical treatment of children with
      Early Onset Scoliosis (EOS). There is documented variation in the treatment of
      this patient population. Previous work building consensus for the approach to
      high risk patients (eg, neuromuscular etiology) has been promising. The goal of
      the current study is to apply similar principles to develop consensus-based
      guidelines for the treatment of patients with EOS. METHODS: A focus group from 2
      multicenter pediatric spine deformity study groups developed a list of statements
      to be distributed to a larger group of EOS experts. Using the Delphi process,
      participants were presented with a systematic review of the literature as well as
      a review of current practices in growth friendly surgery. The first round was
      conducted using an electronic survey. Results of this survey were then discussed
      face-to-face and the statements were further refined. A final round was conducted
      using the Audience Response System, allowing participants to vote for each
      statement (strongly agree or agree). Agreement >80% or disagreement <20% was
      considered consensus. RESULTS: A total of 29 of 57 statements reached consensus.
      Negative statements (statements of disagreement) were excluded, so the final
      consensus guidelines included 22 statements. The number of statements from the
      previously published Best Practice Guidelines (BPG) approved for insertion and
      lengthening growth friendly procedures were 12 of 14 and 11 of 14, respectively.
      The high risk BPG therefore does not cover all of the issues specific to the EOS
      population, and explains why 22 statements reached consensus in the current
      guideline. Upon completion of the surveys, 100% of the participants agreed to
      support its publication. CONCLUSIONS: Using the Delphi process several "best
      practices" were developed for growth friendly surgical treatment of EOS. LEVEL OF
      EVIDENCE: Level V.

PMID- 29064873
TI  - No Significant Association Between the Transfusion of Small Volumes of Leukocyte
      Depleted Red Blood Cells and Mortality Over 7 Years of Follow-up in Patients
      Undergoing Cardiac Surgery: A Propensity Score Matched Analysis.
AB  - BACKGROUND: The impact of red blood cell (RBC) transfusion on long-term clinical
      outcome is controversial. METHODS: We prospectively recorded follow-up data of
      6124 cardiac surgical patients who received no transfusion (RBC- group) or 1-2
      units of leukocyte-depleted RBC (RBC+ group) at our institution. The primary end
      point was overall mortality up to 7 years after cardiac surgery; secondary end
      point was coronary artery revascularization during follow-up. To correct for
      nonrandomized group assignment, propensity score (PS) matching was performed. A
      subgroup analysis was also performed in patients with preoperative anemia.
      RESULTS: PS matching was possible in 4118 patients. During a mean follow-up of
      4.05 years (range, 0.0-7.3 years), 140 patients (14.6%) died in the RBC- group
      and 173 (17.2%) died in the RBC+ group. The hazard ratio for the RBC+ group
      versus the RBC- group was 1.00 (95% confidence interval, 0.79-1.25; P = .969).
      The number of revascularizations was 96 (9.9%) and 125 (10.6%), respectively,
      with a hazard ratio of 1.21 (95% confidence interval, 0.92-1.58; P = .166) for
      the RBC+ group. Preoperative anemia was not a risk factor for postoperative
      mortality, even when patients were transfused. CONCLUSIONS: This PS-matched
      analysis does not provide evidence for an association of the transfusion of small
      volumes of leukocyte-depleted RBCs with an increased postoperative mortality in
      cardiac surgical patients. Moreover, preoperative anemia could not be identified
      as a risk factor for increased postoperative mortality.

PMID- 29064872
TI  - No Differences in Renal Function between Balanced 6% Hydroxyethyl Starch
      (130/0.4) and 5% Albumin for Volume Replacement Therapy in Patients Undergoing
      Cystectomy: A Randomized Controlled Trial.
AB  - BACKGROUND: The use of artificial colloids has declined in critical care, whereas
      they are still used in perioperative medicine. Little is known about the
      nephrotoxic potential in noncritically ill patients during routine surgery. The
      objective of this trial was to evaluate the influences of albumin 5% and balanced
      hydroxyethyl starch 6% (130/0.4) on renal function and kidney injury. METHODS:
      One hundred urologic patients undergoing elective cystectomy were randomly
      assigned for this prospective, single-blinded, controlled study with two parallel
      groups to receive either albumin 5% or balanced hydroxyethyl starch 6% (130/0.4)
      as the only perioperative colloid. The primary endpoint was the ratio of serum
      cystatin C between the last visit at day 90 and the first preoperative visit.
      Secondary endpoints were estimated glomerular filtration rate and serum
      neutrophil gelatinase-associated lipocalin until the third postoperative day and
      risk, injury, failure, loss, and end-stage renal disease criteria at
      postoperative days 3 and 90. RESULTS: The median cystatin C ratio was 1.11
      (interquartile range, 1.01 to 1.23) in the albumin and 1.08 (interquartile range,
      1.00 to 1.20) in the hydroxyethyl starch group (median difference = 0.03; 95% CI,
      -0.09 to 0.08; P = 0.165). Also, there were no significant differences concerning
      serum cystatin C concentrations; estimated glomerular filtration rate; risk,
      injury, failure, loss, and end-stage renal disease criteria; and neutrophil
      gelatinase-associated lipocalin. Infusion requirements, transfusion rates, and
      perioperative hemodynamics were similar in both groups. CONCLUSIONS: With respect
      to renal function and kidney injury, this study indicates that albumin 5% and
      balanced hydroxyethyl starch 6% have comparable safety profiles in noncritically
      ill patients undergoing major surgery.

PMID- 29064874
TI  - Continuous Pulse Oximetry and Capnography Monitoring for Postoperative
      Respiratory Depression and Adverse Events: A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Death and anoxic brain injury from unrecognized postoperative
      respiratory depression (PORD) is a serious concern for patient safety. The
      American Patient Safety Foundation has called for continuous electronic
      monitoring for all patients receiving opioids in the postoperative period. These
      recommendations are based largely on consensus opinion with currently limited
      evidence. The objective of this study is to review the current state of knowledge
      on the effectiveness of continuous pulse oximetry (CPOX) versus routine nursing
      care and the effectiveness of continuous capnography monitoring with or without
      pulse oximetry for detecting PORD and preventing postoperative adverse events in
      the surgical ward. METHODS: We performed a systematic search of the literature
      databases published between 1946 and May 2017. We selected the studies that
      included the following: (1) adult surgical patients (>18 years old); (2)
      prescribed opioids during the postoperative period; (3) monitored with CPOX
      and/or capnography; (4) primary outcome measures were oxygen desaturation,
      bradypnea, hypercarbia, rescue team activation, intensive care unit (ICU)
      admission, or mortality; and (5) studies published in the English language. Meta
      analysis was performed using Cochrane Review Manager 5.3. RESULTS: In total, 9
      studies (4 examining CPOX and 5 examining continuous capnography) were included
      in this systematic review. In the literature on CPOX, 1 randomized controlled
      trial showed no difference in ICU transfers (6.7% vs 8.5%; P = .33) or mortality
      (2.3% vs 2.2%). A prospective historical controlled trial demonstrated a
      significant reduction in ICU transfers (5.6-1.2 per 1000 patient days; P = .01)
      and rescue team activation (3.4-1.2 per 1000 patient days; P = .02) when CPOX was
      used. Overall, comparing the CPOX group versus the standard monitoring group,
      there was 34% risk reduction in ICU transfer (P = .06) and odds of recognizing
      desaturation (oxygen saturation [SpO2] <90% >1 hour) was 15 times higher (P <
      .00001). Pooled data from 3 capnography studies showed that continuous
      capnography group identified 8.6% more PORD events versus pulse oximetry
      monitoring group (CO2 group versus SpO2 group: 11.5% vs 2.8%; P < .00001). The
      odds of recognizing PORD was almost 6 times higher in the capnography versus the
      pulse oximetry group (odds ratio: 5.83, 95% confidence interval, 3.54-9.63; P <
      .00001). No studies examined the impact of continuous capnography on reducing
      rescue team activation, ICU transfers, or mortality. CONCLUSIONS: The use of CPOX
      on the surgical ward is associated with significant improvement in the detection
      of oxygen desaturation versus intermittent nursing spot-checks. There is a trend
      toward less ICU transfers with CPOX versus standard monitoring. The evidence on
      whether the detection of oxygen desaturation leads to less rescue team activation
      and mortality is inconclusive. Capnography provides an early warning of PORD
      before oxygen desaturation, especially when supplemental oxygen is administered.
      Improved education regarding monitoring and further research with high-quality
      randomized controlled trials is needed.

PMID- 29064875
TI  - Perioperative Patient Blood Management to Improve Outcomes.
AB  - Anemia is common in elective surgery and is an independent risk factor for
      morbidity and mortality. Historical management of anemia has focused on the use
      of allogeneic blood transfusion but this in itself is not without risk. It too
      has been independently associated with morbidity and mortality, let alone the
      costs and relative shortage of this resource. In recognition of this, patient
      blood management (PBM) shifts the focus from the product to the patient and views
      the patient's own blood as a resource that should be conserved and managed
      appropriately as a standard of care. It consists of 3 pillars: the optimization
      of red blood cell mass; reduction of blood loss and bleeding; and optimization of
      the patient's physiological tolerance toward anemia. Integration of these 3
      pillars in the form of multimodal care bundles and strategies into perioperative
      pathways should improve care processes and patient outcome. Preoperative anemia
      is most commonly caused by functional iron deficiency and should be treated with
      oral iron, intravenous iron, and/or recombinant erythropoietin. An individualized
      assessment of the thrombotic risk of discontinuing anticoagulant and antiplatelet
      medication should be balanced against the risk of perioperative bleeding.
      Neuraxial anesthetic techniques should be considered and minimally invasive
      surgery undertaken where appropriate. Cell salvage should be used if significant
      blood loss is anticipated and pharmacological treatments such as tranexamic acid
      and fibrin sealants have been shown to reduce blood loss. Point of care tests can
      guide the perioperative management of dynamic coagulopathy. Blood testing
      sampling should be performed only when indicated and when taken, sample volume
      and waste should be minimized. Restrictive blood transfusion thresholds and
      reassessment after single unit transfusion should be incorporated into clinical
      practice where appropriate. For PBM to become standard practice in routine
      surgical care, national health care quality change initiatives must set the
      agenda for change but the patient-centered approach to PBM should be delivered in
      a way that is also hospital centered. Characterization of the current practice of
      PBM at each hospital is crucial to facilitate the benchmarking of performance.
      Barriers to effective implementation such as lack of knowledge should be
      identified and acted on. Continuous audit of practice with a focus on transfusion
      rates and patient outcomes can identify areas in need of improvement and provide
      iterative feedback to motivate and inspire the main stakeholders.

PMID- 29064876
TI  - Incidence of Anaphylaxis Associated With Sugammadex.
AB  - We retrospectively investigated the incidence of potential sugammadex-induced
      anaphylaxis at a single center in Japan over a period of 3 years. The overall
      incidence of intraoperative hypersensitivity reaction was 0.22% (95% confidence
      interval [CI], 0.17%-0.29%), and the incidence of anaphylaxis was 0.059% (95% CI,
      0.032%-0.10%). The total number of patients who received sugammadex during the
      study period was 15,479, and the incidence of anaphylaxis associated with
      sugammadex was 0.039% (n = 6; 95% CI, 0.014%-0.084%). This result implies that
      the incidence of sugammadex-associated anaphylaxis could be as high as that for
      succinylcholine or rocuronium. A prospective study, including testing for
      identification of cause, is necessary to confirm the exact incidence of
      sugammadex-induced anaphylaxis; however, the present finding calls attention to
      this potential.

PMID- 29064877
TI  - Evidence Basis for Regional Anesthesia in Ambulatory Arthroscopic Knee Surgery
      and Anterior Cruciate Ligament Reconstruction: Part II: Adductor Canal Nerve
      Block-A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Adductor canal block (ACB) has emerged as an effective analgesic
      regional technique for major knee surgeries in the last decade. Its motor-sparing
      properties make it particularly attractive for ambulatory knee surgery, but
      evidence supporting its use in ambulatory arthroscopic knee surgery is
      conflicting. This systematic review and meta-analysis evaluates the analgesic
      effects of ACB for ambulatory arthroscopic knee surgeries. METHODS: We conducted
      a comprehensive search of electronic databases for randomized controlled trials
      examining the analgesic effects of ACB compared to control or any other analgesic
      modality. Both minor arthroscopic and anterior cruciate ligament reconstruction
      (ACLR) surgeries were considered. Rest and dynamic pain scores, opioid
      consumption, opioid-related adverse effects, time to first analgesic request,
      patient satisfaction, quadriceps strength, and block-related complications were
      evaluated. Data were pooled using random-effects modeling. RESULTS: Our search
      yielded 10 randomized controlled trials comparing ACB with placebo or femoral
      nerve block (FNB); these were subgrouped according to the type of knee surgery.
      For minor knee arthroscopic surgery, ACB provided reduced postoperative resting
      pain scores by a mean difference (95% confidence interval) of -1.46 cm (-2.03 to 
      0.90) (P < .00001), -0.51 cm (-0.92 to -0.10) (P = .02), and -0.48 cm (-0.93 to 
      0.04) (P = .03) at 0, 6, and 8 hours, respectively, compared to control. Dynamic
      pain scores were reduced by a mean difference (95% confidence interval) of -1.50
      cm (-2.10 to -0.90) (P < .00001), -0.50 cm (-0.95 to -0.04) (P = .03), and -0.59
      cm (-1.12 to -0.05) (P = .03) at 0, 6, and 8 hours, respectively, compared to
      control. ACB also reduced the cumulative 24-hour oral morphine equivalent
      consumption by -7.41 mg (-14.75 to -0.08) (P = .05) compared to control. For ACLR
      surgery, ACB did not provide any analgesic benefits and did not improve any of
      the examined outcomes, compared to control. ACB was also not different from FNB
      for these outcomes. CONCLUSIONS: After minor ambulatory arthroscopic knee
      surgery, ACB provides modest analgesic benefits, including improved relief for
      rest pain, and reduced opioid consumption for up to 8 and 24 hours, respectively.
      The analgesic benefits of ACB are not different from placebo or FNB after
      ambulatory ACLR, suggesting a limited role of both blocks in this procedure.
      Paucity of trials dictates cautious interpretation of these findings. Future
      studies are needed to determine the role of ACB in the setting of local
      anesthetic instillation and/or graft donor-site analgesia.

PMID- 29064879
TI  - The Successful Implementation of a Modified Enhanced Recovery After Surgery
      (ERAS) Program for Bariatric Surgery in a South African Teaching Hospital.
AB  - BACKGROUND: This study assessed the impact of strict adherence to perioperative
      pathways incorporating an enhanced recovery after surgery protocol on the
      outcomes of bariatric surgery at our center. METHODS: Prospective data were
      collected on 62 patients undergoing bariatric surgery between January 2011 and
      March 2016. Outcomes were compared between those who adhered to the perioperative
      pathway and those who did not. RESULTS: Fifty-three patients underwent
      laparoscopic sleeve gastrectomy, and 9 patients underwent Laparoscopic Roux-en-Y
      Gastric Bypass. The majority of subjects were female individuals (n=45; 72.6%).
      The mean age (+/-SD) was 40.5+/-9.8 years (range, 21 to 59 y). The mean
      preoperative body mass index (BMI) was 54.8+/-11.0. The mean BMI loss from
      baseline was 14.8 kg/m (-15.9 kg m; P<0.001). There were no deaths, and there
      were only 2 postoperative complications (1 intra-abdominal bleeding
      postoperatively requiring reoperation and 1 patient requiring CPAP support in
      intensive care unit). Full adherence was achieved in 53 (85.5%) patients with a
      mean length of stay (LOS) of 3+/-0.8 days. The nonadherent group had a
      significantly longer LOS of 4+/-3.2 days (P=0.049). The time since last follow-up
      visit was on average 4.4+/-5.6 months in the fully adherent group and
      significantly longer in the nonadherent group at 10.6+/-11.3 months (P=0.013).
      Age, race, sex, and BMI did not significantly impact on adherence. The mean LOS
      among morbidly obese and super obese patients was comparable at 3 and 3.3 days,
      respectively (P=0.442). CONCLUSION: Adherence to enhanced recovery after surgery
      pathways was associated with a significantly shorter hospital stay and better
      follow-up in our surgical unit.

PMID- 29064880
TI  - Usefulness of the Transoral Anvil Delivery System for Esophagojejunostomy After
      Laparoscopic Total Gastrectomy: A Single-institution Comparative Study of
      Transoral Anvil Delivery System and the Overlap Method.
AB  - PURPOSE: Many reconstruction techniques have been reported after laparoscopic
      total gastrectomy (LTG), but it is not clear which anastomosis technique is most
      useful, and no standard methods have been established. This study examined
      whether LTG using the transoral anvil delivery system (TOADS) is a feasible and
      safe procedure for gastric cancer. MATERIALS AND METHODS: A series of 47 patients
      underwent the overlap method and 36 underwent the hemi-double-stapling technique
      with TOADS. Intraoperative and postoperative outcomes were compared between the 2
      groups. RESULTS: In the TOADS group, operation time for reconstruction was
      shorter (16+/-3 vs. 45+/-10 min, P=0.003), and blood loss was reduced (45+/-15
      vs. 126+/-13 mL, P=0.0002). There were no significant differences in
      intraoperative complications, conversion to open surgery, and intraoperative
      anastomosis-related complications between the 2 groups. Furthermore, there were
      no significant differences in the incidence of complications, reoperation,
      mortality, and postoperative hospital stay. CONCLUSION: LTG using TOADS for
      gastric cancer may be a technically feasible surgical procedure with acceptable
      morbidity.

PMID- 29064881
TI  - Propylene Glycol in Contact Dermatitis: A Systematic Review.
AB  - Propylene glycol (PG), an emollient and emulsifier found in cosmetics,
      medications, and food, has been granted the dubious honor of being named the
      American Contact Dermatitis Society's Allergen of the Year for 2018. Contact,
      systemic, and irritant cutaneous reactions have been documented for PG, which has
      become an increasingly common ingredient. Propylene glycol is as contentious as
      it is ubiquitous because it acts as both a weak sensitizer and an irritant,
      confounding the results of positive patch tests. This review serves to delve into
      what we know about PG from previous reports and studies so that providers will
      have a better understanding of PG contact dermatitis.

PMID- 29064882
TI  - CrossFit-Associated Allergic Contact Dermatitis.

PMID- 29064883
TI  - Patch Testing with Decyl and Lauryl Glucoside: How Well Does One Screen for
      Contact Allergic Reactions to the Other?
AB  - BACKGROUND: Alkyl glucoside surfactants, present in many cosmetic products, can
      cause allergic contact dermatitis. Decyl glucoside has been part of the North
      American Contact Dermatitis Group standard allergen panel since 2009. OBJECTIVES:
      This study aimed to identify rates and relevance of positive patch test reactions
      to decyl and lauryl glucosides and to determine how well one of these glucosides
      screens for contact allergic reactions to the other. METHODS: A retrospective
      analysis was performed on 897 patients suspected of having a cosmetic-related
      dermatitis and patch tested with both decyl and lauryl glucosides between 2009
      and 2016. RESULTS: Forty-eight patients (5%) had positive reactions to decyl
      glucoside and/or lauryl glucoside. Among the alkyl glucoside-allergic patients,
      65% had positive reactions to both decyl and lauryl glucosides. In 41% of cases,
      reactions were of definite or probable relevance. In approximately 55% of cases,
      reactions were of possible relevance. CONCLUSIONS: Sixty-five percent of
      glucoside-allergic patients exhibited co-reactions to decyl and lauryl
      glucosides. Thus, neither glucoside is an adequate screen for allergy to the
      other. Given that these reactions are often relevant, clinicians should patch
      test with decyl, lauryl, and other alkyl glucosides in cases of suspected
      cosmetic allergy.

PMID- 29064884
TI  - Efficacy of Preoperative Oral Antibiotic Prophylaxis for the Prevention of
      Surgical Site Infections in Patients with Crohn Disease: A Randomized Controlled
      Trial.
AB  - OBJECTIVES: We investigated the efficacy of oral antimicrobial prophylaxis in
      patients undergoing surgery for Crohn disease. BACKGROUND: Although oral
      antibiotic prophylaxis with mechanical bowel preparation has been recommended for
      colorectal surgery, the use of this approach remains somewhat controversial.
      Moreover, the efficacy of this approach for inflammatory bowel disease also
      remains unclear. METHODS: This study was conducted as a randomized controlled
      trial at the Hyogo College of Medicine. The study protocols were registered with
      the University Hospital Medical Information Network Clinical Trials Registry
      (000013369). In this study, 335 patients with Crohn disease who were scheduled to
      undergo intestinal resection with an open approach were randomly assigned to
      either group A or group B. The patients in group A received both preoperative
      oral antibiotics and intravenous antimicrobial prophylaxis, and intravenous
      antimicrobial prophylaxis alone was given to the patients in group B. All
      patients underwent preoperative mechanical bowel preparation with sodium
      picosulfate hydrate. The primary endpoint of this study was the incidence of
      surgical site infection (SSI) according to an intention-to-treat analysis.
      RESULTS: Although the incidences of overall and organ/space SSI were not
      significantly different, the incidence of incisional SSI was significantly lower
      in group A (12/163; 7.4%) than in group B (27/162; 16.6%) (P = 0.01). In the
      multivariate analysis, the absence of oral antibiotic prophylaxis was an
      independent risk factor for incisional SSI (odds ratio: 3.3; 95% confidence
      interval: 1.3-8.3; P = 0.01). CONCLUSIONS: Combined oral and intravenous
      antimicrobial prophylaxis in patients with Crohn disease contributed to the
      prevention of SSI.

PMID- 29064886
TI  - What We Learned From John Cameron.

PMID- 29064887
TI  - Adherence to Enhanced Recovery Protocols in NSQIP and Association With Colectomy
      Outcomes.
AB  - OBJECTIVE: To evaluate the effect of protocol adherence on length of stay (LOS)
      and recovery-specific outcomes after colectomy. BACKGROUND: Enhanced recovery
      protocols (ERPs) may decrease postoperative morbidity and LOS; however, the
      effect of overall protocol adherence remains unclear. METHODS: Using American
      College of Surgeons' National Surgical Quality Improvement Program colectomy data
      (July 2014-December 2015) and 13 novel ERP variables, propensity scores were
      constructed for low (0-5), moderate (6-9), and high adherence (10-13 components).
      Prolonged LOS (>75th percentile, uncomplicated cases) was modeled with
      multivariable logistic regression with robust standard errors, adjusted for
      hospital-level clustering and propensity score. Secondary recovery-specific
      outcomes were modeled with negative binomial regression. Subgroup analysis was
      conducted on uncomplicated cases. RESULTS: Among 8139 elective colectomies at 113
      hospitals, LOS increased with decreasing adherence (4.3 days [SD 3.3] high
      adherence vs 7.8 [SD 6.8] low adherence; P < 0.0001). High adherence was
      associated with fewer complications, including postoperative ileus, compared with
      moderate (P < 0.0001) and low adherence (P < 0.0001). High-adherence patients
      achieved recovery milestones earlier (vs low adherence), with return of bowel
      function at 1.9 (vs 3.7) days, tolerance of diet at 2.4 (vs 5.4) days, and oral
      pain control at 2.7 (vs 5.0) days (P < 0.0001). Risk-adjusted odds of prolonged
      LOS were significantly increased for low (odds ratio 2.7, 95% confidence interval
      2.0-3.6) and moderate-adherence (odds ratio 1.7, 95% confidence interval 1.4-2.1)
      groups. In a negative binomial regression, time to recovery was 60% to 95% longer
      for low versus high adherence (P < 0.0001). CONCLUSIONS: In this large, multi
      institutional North American data registry, high adherence to ERPs was associated
      with earlier recovery, decreased complications, and shorter LOS. ERPs can improve
      outcomes; however, benefits correlate with adherence.

PMID- 29064888
TI  - Response: "We Still in an Update Process of the BCLC System".

PMID- 29064885
TI  - Transplantation Versus Resection for Hilar Cholangiocarcinoma: An Argument for
      Shifting Treatment Paradigms for Resectable Disease.
AB  - OBJECTIVE: To investigate the influence of type of surgery (transplant vs
      resection) on overall survival (OS) in patients with hilar cholangiocarcinoma (H
      CCA). BACKGROUND: Outcomes after resection for H-CCA are poor, yet
      transplantation is currently only reserved for well-selected patients with
      unresectable disease. METHODS: All patients with H-CCA who underwent resection
      from 2000 to 2015 at 10 institutions were included. Three institutions
      additionally had active H-CCA transplant protocols with similar selection
      criteria over similar time periods. RESULTS: Of 304 patients with suspected H
      CCA, 234 underwent attempted resection and 70 were enrolled in a transplant
      protocol. Excluding incomplete/R2 resections (n = 43), patients who were
      enrolled, but did not undergo transplant (n = 24), and transplants without
      confirmed H-CCA diagnoses (n = 5), 191 patients underwent curative-intent
      resection and 41 curative-intent transplant. Compared with resection, transplant
      patients were younger (52 vs 65 years; P < 0.001), and more frequently had
      primary sclerosing cholangitis (PSC; 61% vs 2%; P < 0.001) and received
      chemotherapy and/or radiation (98% vs 57%; P < 0.001). Groups were otherwise
      similar in demographics and comorbidities. Patients who underwent transplant for
      confirmed H-CCA diagnosis had improved OS compared with resection (3-year: 72% vs
      33%; 5-year: 64% vs 18%; P < 0.001). Among patients who underwent resection for
      tumors <3 cm with lymph-node negative disease, and excluding PSC patients,
      transplant was still associated with improved OS (3-year: 54% vs 44%; 5-year: 54%
      vs 29%; P = 0.03). Transplant remained associated with improved survival on
      intention-to-treat analysis, even after accounting for tumor size, lymph node
      status, and PSC (P = 0.049). CONCLUSIONS: Resection for hilar cholangiocarcinoma
      that meets criteria for transplantation (<3 cm, lymph-node negative disease) is
      associated with substantially decreased survival compared to transplant for the
      same criteria with unresectable disease. Prospective trials are needed and
      justified.

PMID- 29064889
TI  - Impact of Sarcopenic Obesity on Outcomes in Patients Undergoing Hepatectomy for
      Hepatocellular Carcinoma.
AB  - OBJECTIVE: To evaluate preoperative body composition, including skeletal muscle
      and visceral adipose tissue, and to clarify the impact on outcomes after
      hepatectomy for hepatocellular carcinoma (HCC). BACKGROUND: Recent studies have
      indicated that sarcopenia is associated with morbidity and mortality in various
      pathologies, including cancer, and that obesity or visceral adiposity represents
      a significant risk factor for several cancers. However, the impact of sarcopenic
      obesity on outcomes after hepatectomy for HCC has not been fully investigated.
      METHODS: We retrospectively analyzed 465 patients who underwent primary
      hepatectomy for HCC between April 2005 and March 2015. Skeletal muscle mass and
      visceral adipose tissue were evaluated by preoperative computed tomography to
      define sarcopenia and obesity. Patients were classified into 1 of 4 body
      composition groups according to the presence or absence of sarcopenia and
      obesity. RESULTS: Body composition was classified as nonsarcopenic nonobesity in
      184 patients (39%), nonsarcopenic obesity in 219 (47%), sarcopenic nonobesity in
      31 (7%), and sarcopenic obesity in 31 (7%). Compared with patients with
      nonsarcopenic nonobesity, patients with sarcopenic obesity displayed worse median
      survival (84.7 vs. 39.1 mo, P = 0.002) and worse median recurrence-free survival
      (21.4 vs. 8.4 mo, P = 0.003). Multivariate analysis identified sarcopenic obesity
      as a significant risk factor for death (hazard ratio [HR] = 2.504, P = 0.005) and
      HCC recurrence (HR = 2.031, P = 0.006) after hepatectomy for HCC. CONCLUSION:
      Preoperative sarcopenic obesity was an independent risk factor for death and HCC
      recurrence after hepatectomy for HCC.

PMID- 29064890
TI  - Carotid Artery Reactivity Predicts Events in Peripheral Arterial Disease
      Patients.
AB  - OBJECTIVE: Patients with peripheral arterial disease (PAD) have increased risk on
      future cerebro- and cardiovascular events. Our aim was to examine whether carotid
      artery reactivity (CAR; a novel, simple procedure to examine endothelial
      function) predicts cardiovascular events in PAD patients. BACKGROUND: Increased
      risk for future cardiovascular events in PAD patients is likely related to
      endothelial dysfunction, highlighting the necessity for simple assessment of
      endothelial function. METHODS: A total of 172 PAD patients (68 +/- 10 years, 67%
      male) underwent the CAR, which involves ultrasound measurement of carotid artery
      diameter during sympathetic stimulation produced by 90-second hand immersion in 4
      degrees C ice-water (ie, cold pressor test). CAR-responses were dichotomized into
      carotid constriction or dilation. We recorded cardiac and cerebrovascular events,
      mortality, and clinical progression to percutaneous transluminal angioplasty or
      loss of patency during 12-month follow-up. RESULTS: Eighty-two PAD patients
      demonstrated carotid constriction and 90 patients demonstrated dilation. PAD
      patients with carotid constriction showed more cardiovascular events compared to
      patients with dilation (Kaplan-Meier Log rank; P < 0.05). Cox proportional hazard
      models showed that patients with carotid constriction continued to show higher
      risk for cardiovascular events [hazard ratio: 4.1; 95% confidence interval (CI),
      1.3-12.5] and clinical progression (hazard ratio: 2.0; 95% CI, 1.2-3.3), even
      after adjustment for other risk factors. Ankle brachial pressure index and
      carotid intima-medial thickness alone did not predict (cardiovascular) event or
      improve risk assessment beyond that provided by CAR. CONCLUSION: Carotid
      vasoconstriction identifies PAD patients with a 4-fold increased risk for future
      cardiovascular events and 2-fold increased risk for clinical deterioration. CAR
      provides a simple, novel strategy to predict cardiovascular events and
      progression in PAD patients. CLINICAL TRIAL REGISTRATION:
      www.trialregister.nl/trialreg/index.asp, NTR-4117.

PMID- 29064891
TI  - How Many Observations are Needed to Assess a Surgical Trainee's State of
      Operative Competency?
AB  - OBJECTIVE: To establish the number of operative performance observations needed
      for reproducible assessments of operative competency. BACKGROUND: Surgical
      training is transitioning from a time-based to a competency-based approach, but
      the number of assessments needed to reliably establish operative competency
      remains unknown. METHODS: Using a smart phone based operative evaluation
      application (SIMPL), residents from 13 general surgery training programs were
      evaluated performing common surgical procedures. Two competency metrics were
      investigated separately: autonomy and overall performance. Analyses were
      performed for laparoscopic cholecystectomy performances alone and for all
      operative procedures combined. Variance component analyses determined operative
      performance score variance attributable to resident operative competency and
      measurement error. Generalizability and decision studies determined number of
      assessments needed to achieve desired reliability (0.80 or greater) and determine
      standard errors of measurement. RESULTS: For laparoscopic cholecystectomy, 23
      ratings are needed to achieve reproducible autonomy ratings and 17 ratings are
      needed to achieve reproducible overall operative performance ratings. For the
      undifferentiated mix of procedures, 60 ratings are needed to achieve reproducible
      autonomy ratings and 40 are needed for reproducible overall operative performance
      ratings. CONCLUSION: The number of observations needed to achieve reproducible
      assessments of operative competency far exceeds current certification
      requirements, yet remains an important and achievable goal. Attention should also
      be paid to the mix of cases and raters in order to assure fair judgments about
      operative competency and fair comparisons of trainees.

PMID- 29064892
TI  - A Novel Method of Setting Performance Standards in Surgery Using Patient
      Outcomes.
AB  - OBJECTIVE: To describe a novel, outcome-based method of standard setting that
      differentiates between clinical outcomes rather than arbitrary educational goals.
      BACKGROUND: Standard setting methods used in assessments of procedural skill are
      currently not evidence-driven or outcome-based. This represents a potential
      obstacle for the broad implementation of these evaluations in summative
      assessments such as certification and credentialing. METHODS: The concept is
      based on deriving a receiver operating characteristic curve from a regression
      model that incorporates measures of intraoperative surgeon performance and
      confounding patient characteristics. This allows the creation of a performance
      standard that best predicts a clinically significant outcome of interest. The
      discovery cohort used to create the predictive model was derived from pilot data
      that used the Global Evaluative Assessment of Robotic Skill assessment tool to
      predict patient urinary continence 3 months following robotic-assisted radical
      prostatectomy. RESULTS: A receiver operating characteristic curve with an area
      under the curve of 0.75 was created from predicted probability statistic
      generated by the predictive model. We chose a predicted probability of 0.35,
      based on an optimal tradeoff in sensitivity and specificity (Youden Index).
      Rearranging the regression equation, we determined the performance score required
      to predict a 35%, patient-adjusted probability of postoperative urinary
      incontinence. CONCLUSIONS: This novel methodology is context, patient, and
      assessment-specific. Current standard setting methods do not account for the
      heterogeneity of the clinical environment. Workplace-based assessments in
      competency-based medical education require standards that are credible to the
      educator and the trainee. High-stakes assessments must ensure that surgeons have
      been evaluated to a standard that prioritizes satisfactory patient outcomes and
      safety.

PMID- 29064893
TI  - Time of Metastasis and Outcome in Colorectal Cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes of metastases at
      various time intervals after colorectal cancer (CRC) diagnosis. BACKGROUND:
      Earlier studies have indicated a short time interval between CRC diagnosis and
      distant metastases to be associated with poor prognosis. The majority of studies
      assessed outcome from CRC diagnosis or metastasis resection rather than from
      metastasis diagnosis and might be subject to immortal time bias. METHODS:
      Patients in the population-based DACHS study were stratified: metastases
      at/within 1 month (immediate), 2 to 6 months (early), 7 to 12 months
      (intermediate), and >12 months (late) after CRC diagnosis. The primary endpoint
      was overall survival (OS) from metastasis diagnosis. Cox proportional hazards
      regression models were used to calculate hazard ratios (HRs) and 95% confidence
      intervals (CI). HRs were adjusted for important confounders and immortal time.
      RESULTS: A total of 1027 patients were included. T4 (P < 0.0001) and node
      positive tumors (P < 0.0001) were more frequent in the immediate group. Lung
      metastases (P < 0.0001) and single-site metastases (P < 0.0001) were more
      prevalent in the late group. In multivariable analysis, immediate metastases were
      not associated with poor OS compared to metastases at later time points (late vs
      immediate: HR 1.21; 95% CI, 0.98-1.48). Subgroup analyses revealed poor OS of
      late versus immediate metastases for females (1.45; 1.08-1.96), proximal colon
      cancer (1.54; 1.09-2.16), and N0 (1.46; 1.00-2.12) or N1 disease (1.88; 1.17
      3.05). CONCLUSIONS: Immediate or early metastases are not associated with
      unfavorable outcome compared to late metastases. These findings challenge the
      current notion of poor outcome for CRC with immediate or early metastases.

PMID- 29064894
TI  - Transcatheter Arterial Embolization Compared With Surgery for Uncontrolled Peptic
      Ulcer Bleeding: A Population-based Cohort Study.
AB  - OBJECTIVE: To compare key outcomes after transcatheter arterial embolization
      (TAE) with conventional surgery for peptic ulcer bleeding when endoscopic
      intervention fails to achieve hemostasis. BACKGROUND: Mortality in peptic ulcer
      bleeding remains high, especially in patients who require surgical treatment.
      METHODS: A population-based cohort study in Stockholm, Sweden, in 2000 to 2014,
      assessing the main outcome all-cause mortality and the secondary outcomes re
      bleeding, re-intervention, length of hospitalization, and complications, was
      conducted. Data were taken from well-maintained registries and medical records.
      Multivariable Cox-regression provided hazard ratios (HRs) with 95% confidence
      intervals (CIs) adjusted for age, sex, ulcer history, comorbidity, and calendar
      period were considered. RESULTS: Included were 282 patients, 97 in the TAE group
      and 185 in the surgery group. Compared with the surgery group, the overall hazard
      of death was 34% decreased in the TAE group (adjusted HR 0.66, 95% CI 0.46-0.96).
      The corresponding HRs for mortality within 30 days, 90 days, 1 year, and 5 years
      were 0.70 (95% CI 0.37-1.35), 0.69 (95% CI 0.38-1.26), 0.88 (95% CI 0.53-1.47),
      and 0.67 (95% CI 0.45-1.00), respectively. The risk of re-bleeding was higher
      after TAE compared with surgery (HR 2.48, 95% CI 1.33-4.62). The median length of
      hospital stay was shorter in the TAE group-8 versus 16 days-acceleration factor
      0.59 (95% CI 0.45-0.77) and the risk of complications was lower (8.3% vs 32.2%; P
      < 0.0001). CONCLUSIONS: This study indicates that TAE compares favorably with
      surgery regarding prognosis after refractory peptic ulcer bleeding, and the
      shorter length of hospital stay and fewer complications outweigh a higher risk of
      re-bleeding. TAE could be recommended as first-line treatment for these patients.

PMID- 29064895
TI  - Nurse Telephonic Triage Service for After-hour Patient Calls in Neurosurgery.
AB  - OBJECTIVE: The aim of this study was to report the utilization and experience of
      the nurse telephonic triage service for after-hour patient calls in Neurosurgery.
      BACKGROUND: It is challenging for patients to reach their clinicians after-hours
      in a timely manner. This may result in worse health outcomes for the patients, or
      inappropriate utilization of emergency rooms and urgent care facilities.
      Physicians continue to remain overwhelmed with frequent after-hours calls in
      addition to other clinical responsibilities while on-call. METHODS: In August
      2015, our institution launched the Clinical Advice Service (CAS) to provide a
      patient-centric, nurse-run telephone triage service for after-hour calls from
      Neurosurgery patients. Clinical protocols were created for use by CAS staff by
      Neurosurgery clinicians. RESULTS: Between July 2016 and June 2017, CAS has
      accepted 1021 after-hours calls from Neurosurgery patients. A total of 71.4% of
      these calls were clinical, and the remaining nonclinical (directions,
      appointments, general information). CAS escalated 37.3% of the calls to the on
      call Neurosurgery physician; 4.8% Neurosurgery patients were triaged to the
      emergency room by CAS. CONCLUSION: CAS has been able to provide well-coordinated
      care to Neurosurgery patients while reducing physician workload.

PMID- 29064896
TI  - Barriers to Regionalized Surgical Care: Public Perspective Survey and Geospatial
      Analysis.
AB  - OBJECTIVE: To describe public willingness to participate in regionalized surgical
      care for cancer. SUMMARY OF BACKGROUND DATA: Improved outcomes at high-volume
      centers following complex surgery have driven a push to regionalize surgical
      care. Patient attitudes toward regionalization are not well described. METHODS:
      As part of the Cornell National Social Survey, a cross-sectional telephone survey
      was performed. Participants were asked about their willingness to seek
      regionalized care in a hypothetical scenario requiring surgery. Their responses
      were compared with demographic characteristics. A geospatial analysis of hospital
      proximity was performed, as well as a qualitative analysis of barriers to
      regionalization. RESULTS: Cooperation rate was 48.1% with 1000 total respondents.
      They were an average of 50 years old (range 18 to 100 years) and 48.9% female.
      About 49.6% were unwilling to travel 5 hours or more to seek regionalized care
      for improved survival. Age >70 years [odds ratio (OR) 0.34, 95% confidence
      interval (95% CI) 0.19-0.60] and perceived distance to a center >30 minutes (OR
      0.60, 95% CI 0.41-0.86) were associated with decreased willingness to seek
      regionalized care, while high income (OR 2.09, 95% CI 1.39-3.16) was associated
      with increased willingness. Proximity to a major center was not associated with
      willingness to travel (OR 0.92, 95% CI 0.67-1.22). Major perceived barriers to
      regionalization were transportation, life disruption, social support,
      socioeconomic resources, poor health, and remoteness. CONCLUSION: Americans are
      divided on whether the potential for improved survival with regionalization is
      worth the additional travel effort. Older age and lower income are associated
      with reduced willingness to seek regionalized care. Multiple barriers to
      regionalization exist, including a lack of knowledge of the location major
      centers.

PMID- 29064897
TI  - A Proposal to Mitigate the Consequences of Type 2 Error in Surgical Science.

PMID- 29064898
TI  - Open, Laparoscopic, or Robotic Rectal Cancer Surgery: Adjustments for Biases May
      Increase the Differences.

PMID- 29064899
TI  - Variation in Drain Management After Pancreatoduodenectomy: Early Versus Delayed
      Removal.
AB  - OBJECTIVE: The objectives are to report practice patterns and management of
      operatively placed drains and to compare outcomes in patients with early versus
      delayed drain removal after pancreatoduodenectomy. BACKGROUND: Early drain
      removal after pancreatoduodenectomy, when guided by postoperative day (POD) 1
      drain fluid amylase (DFA-1), is associated with reduced rates of clinically
      relevant postoperative pancreatic fistula (CR-POPF). However, whether surgeons
      have altered their management based on this strategy is unknown. METHODS: The
      American College of Surgeons-National Surgical Quality Improvement Program (ACS
      NSQIP) 2014 Participant Use File was queried to identify patients having
      undergone pancreatoduodenectomy (n = 3093). Patients with intraoperatively placed
      drains were stratified according to measurement of DFA-1 and day of drain
      removal. Patients with POD 1 DFA-1 of <=5000 U/L whose drains were removed by POD
      3 were propensity score-matched with patients whose drains were removed after POD
      3. RESULTS: Of 2698 patients, 580 (21.5%) had a DFA-1 recorded. Measurement of
      DFA-1 was associated with earlier time to drain removal and shorter postoperative
      length of stay (P < 0.01). Propensity score matching revealed that early drain
      removal when DFA-1 was <=5000 U/L was associated with significant (P < 0.05)
      reductions in overall morbidity (35.3% vs 52.3%), CR-POPF (0.9% vs 7.9%), and
      length of stay (6 vs 8 days). CONCLUSIONS: Significant variation exists in the
      use of drain fluid amylase in the management and timing of surgical drain removal
      after pancreatoduodenectomy. Clinical outcomes are best when drain fluid amylase
      is low and operatively placed drains are removed by POD 3.

PMID- 29064900
TI  - Use of Prophylactic Mesh When Creating a Colostomy Does Not Prevent Parastomal
      Hernia: A Randomized Controlled Trial-STOMAMESH.
AB  - OBJECTIVE: The aim of this study was to determine whether parastomal hernia (PSH)
      rate can be reduced by using synthetic mesh in the sublay position when
      constructing permanent end colostomy. The secondary aim was to investigate
      possible side-effects of the mesh. BACKGROUND: Prevention of PSH is important as
      it often causes discomfort and leakage from stoma dressing. Different methods of
      prevention have been tried, including several mesh techniques. The incidence of
      PSH is high; up to 78%. METHODS: Randomized controlled double-blinded multicenter
      trial. Patients undergoing open colorectal surgery, including creation of a
      permanent end colostomy, were randomized into 2 groups, with and without mesh. A
      lightweight polypropylene mesh was placed around the colostomy in the sublay
      position. Follow up after 1 month and 1 year. Computerized tomography and
      clinical examination were used to detect PSH at the 1-year follow up. Data were
      analyzed on an intention-to-treat basis. RESULTS: After 1 year, 211 of 232
      patients underwent clinical examination and 198 radiologic assessments. Operation
      time was 36 minutes longer in the mesh arm. No difference in rate of PSH was
      revealed in the analyses of clinical (P = 0.866) and radiologic (P = 0.748) data.
      There was no significant difference in perioperative complications. CONCLUSIONS:
      The use of reinforcing mesh does not alter the rate of PSH. No difference in
      complication rate was seen between the 2 arms. Based on these results, the
      prophylactic use of mesh to prevent PSH cannot be recommended.This is an open
      access article distributed under the Creative Commons Attribution License 4.0
      (CCBY), which permits unrestricted use, distribution, and reproduction in any
      medium, provided the original work is properly cited.
      http://creativecommons.org/licenses/by/4.0.

PMID- 29064901
TI  - Laparoscopic Versus Open Liver Resection for Colorectal Liver Metastases-Which Is
      a More Suitable Standard Practice?

PMID- 29064902
TI  - The Role of Bowel Preparation in Colorectal Surgery: Results of the 2012-2015 ACS
      NSQIP Data.
AB  - OBJECTIVE: To analyze potential benefits with regards to infectious complications
      with combined use of mechanical bowel preparation (MBP) and ABP in elective
      colorectal resections. BACKGROUND: Despite recent literature suggesting that MBP
      does not reduce infection rate, it still is commonly used. The use of oral
      antibiotic bowel preparation (ABP) has been practiced for decades but its use is
      also controversial. METHODS: Patients undergoing elective colorectal resection in
      the 2012 to 2015 American College of Surgeons National Surgical Quality
      Improvement Program cohorts were selected. Doubly robust propensity score
      adjusted multivariable regression was conducted for infectious and other
      postoperative complications. RESULTS: A total of 27,804 subjects were analyzed;
      5471 (23.46%) received no preparation, 7617 (32.67%) received MBP only, 1374
      (5.89%) received ABP only, and 8855 (37.98%) received both preparations. Compared
      to patients receiving no preparation, those receiving dual preparation had less
      surgical site infection (SSI) [odds ratio (OR) = 0.39, P < 0.001], organ space
      infection (OR = 0.56, P <= 0.001), wound dehiscence (OR = 0.43, P = 0.001), and
      anastomotic leak (OR = 0.53, P < 0.001). ABP alone compared to no prep resulted
      in significantly lower rates of surgical site infection (OR = 0.63, P = 0.001),
      organ space infection (OR = 0.59, P = 0.005), anastomotic leak (OR = 0.53, P =
      0.002). MBP showed no significant benefit to infectious complications when used
      as monotherapy. CONCLUSIONS: Combined MBP/ABP results in significantly lower
      rates of SSI, organ space infection, wound dehiscence, and anastomotic leak than
      no preparation and a lower rate of SSI than ABP alone. Combined bowel preparation
      significantly reduces the rates of infectious complications in colon and rectal
      procedures without increased risk of Clostridium difficile infection. For
      patients undergoing elective colon or rectal resection we recommend bowel
      preparation with both mechanical agents and oral antibiotics whenever feasible.

PMID- 29064903
TI  - Vacuum-Assisted Biopsy to Diagnose a Pathological Complete Response in Breast
      Cancer Patients After Neoadjuvant Systemic Therapy.

PMID- 29064904
TI  - Optimal Selection of Breast Cancer Patients for Elimination of Surgery Following
      Neoadjuvant Systemic Therapy.

PMID- 29064905
TI  - Which Is the True Role of Bridging Therapies for HCC Patients Waiting for Liver
      Transplantation?

PMID- 29064906
TI  - Response: "Which is the True Role of Bridging Therapies for HCC Patients Waiting
      for Liver Transplantation?"

PMID- 29064907
TI  - Preparation for the Diversity of 21st Century Surgical Leadership Opportunities
      Demands Diverse Opportunities for "Professional Development".

PMID- 29064909
TI  - Pexacerfont as a CRF1 antagonist for the treatment of withdrawal symptoms in men
      with heroin/methamphetamine dependence: a randomized, double-blind, placebo
      controlled clinical trial.
AB  - We assessed the efficacy of pexacerfont, a CRF1 antagonist, for the treatment of
      withdrawal symptoms. In this randomized, double-blind, placebo-controlled
      clinical trial, male patients with amphetamine or opioid dependence, on the basis
      of the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text
      Revision (DSM-IV-TR), in the age range 18-55 years, received either pexacerfont
      or placebo (300, 200, and 100 mg/day in the first, second, and third week,
      respectively). No antidepressants, behavioral interventions, or substitution
      therapy were administered. Candidates were excluded if they had DSM-IV-TR axis I
      or II disorders (other than depressive/anxiety disorders). The primary outcomes
      were difference in the distribution of positive urine test results for heroin and
      methamphetamine at the end of the trial, and the mean difference in the change in
      the Visual Analog Scale (VAS) score for craving from the baseline to the endpoint
      between the two groups. No significant difference was detected for urine test
      results, but a significant difference was observed for craving scores. Also,
      significant time*treatment interactions were found for all the scales including
      VAS craving, VAS temptation severity, frequency of temptation, Clinical Opiate
      Withdrawal Scale, Amphetamine Withdrawal Questionnaire, Beck Anxiety Inventory,
      and Beck Depression Inventory II. Our findings favor pexacerfont as a potential
      treatment for withdrawal from drug dependence; however, further comprehensive
      studies are warranted.

PMID- 29064910
TI  - A molecular pathway analysis informs the genetic risk for arrhythmias during
      antipsychotic treatment.
AB  - Arrhythmias are a frequent and potentially fatal side effect of antipsychotic
      treatment. Strict ECG monitoring and clinical interviews are the standards used
      to prevent arrhythmias. A biologic predictive tool is missing. The identification
      of a genetic makeup at risk of antipsychotic-induced arrhythmias is the aim of
      the present investigation. The aim of this study was to identify a molecular
      pathway enriched in single nucleotide polymorphisms associated with antipsychotic
      induced QTc modifications. In total, 661 schizophrenic individuals from the CATIE
      study, M=486 (73.52%), mean age=40.92+/-11.02, were included. QTc variation was
      measured as a phase-specific change-created variable. A nested mixed regression
      for a repeated-measures model served in R for the analysis of the clinical and
      treatment-related covariates and molecular pathway analysis. Plink was used for
      the genetic genome-wide analysis. Quality checking was the standard (genotype
      call rate>0.95; minor allele frequency>0.01; Hardy-Weinberg equilibrium<0.0001)
      and the inflation factor was controlled by lambda values. Quetiapine and
      perphenazine were associated with QTc variation during phase 1. No other
      significant association was detected. No significant inflation was detected. A
      number of molecular pathways were associated with QT variation at a conservative
      (adjusted) P value less than 0.05, including pathways related to neuronal wiring
      and collagen biosynthesis, along with pathways related to K+ currents and cardiac
      contraction. Pathways related to neuronal wiring, collagen biosynthesis, and ion
      currents were identified as possibly involved in QTc modifications during
      antispsychotic treatment in SKZ patients.

PMID- 29064911
TI  - Efficacy of antidepressants over placebo is similar in two-armed versus three
      armed or more-armed randomized placebo-controlled trials.
AB  - Previous studies have reported that effect sizes of antidepressants were larger
      in two-armed than in three-armed or more-armed (multiarmed) randomized trials,
      where the probability of being allocated to placebo is lower. However, these
      studies have not taken into account the publication bias, differences among
      antidepressants, or covariance in multiarmed studies, or examined sponsorship
      bias. We searched published and unpublished randomized-controlled trials that
      compared placebo with 21 antidepressants for the acute treatment of major
      depression in adults. We calculated the ratio of odds ratios (ROR) of drug
      response over placebo in two-armed versus multiarmed trials for each
      antidepressant, and then synthesized RORs across all the included antidepressants
      using the multivariate meta-analysis. A random-effects model was used throughout.
      Two hundred and fifty-eight trials (66 two-armed and 192 multiarmed trials; 80
      454 patients; 43.0% with unpublished data) were included in the present analyses.
      The pooled ROR for response of two-armed trials over multiarmed trials was 1.09
      (95% confidence interval: 0.96-1.24). The ROR did not materially change between
      types of antidepressants, publication year, or sponsorship. The differences
      between two-armed versus multiarmed studies were much smaller than were suggested
      in previous studies and were not significant.

PMID- 29064908
TI  - The Southampton Consensus Guidelines for Laparoscopic Liver Surgery: From
      Indication to Implementation.
AB  - OBJECTIVE: The European Guidelines Meeting on Laparoscopic Liver Surgery was held
      in Southampton on February 10 and 11, 2017 with the aim of presenting and
      validating clinical practice guidelines for laparoscopic liver surgery.
      BACKGROUND: The exponential growth of laparoscopic liver surgery in recent years
      mandates the development of clinical practice guidelines to direct the
      speciality's continued safe progression and dissemination. METHODS: A unique
      approach to the development of clinical guidelines was adopted. Three well
      validated methods were integrated: the Scottish Intercollegiate Guidelines
      Network methodology for the assessment of evidence and development of guideline
      statements; the Delphi method of establishing expert consensus, and the AGREE II
      GRS Instrument for the assessment of the methodological quality and external
      validation of the final statements. RESULTS: Along with the committee chairman,
      22 European experts; 7 junior experts and an independent validation committee of
      11 international surgeons produced 67 guideline statements for the safe
      progression and dissemination of laparoscopic liver surgery. Each of the
      statements reached at least a 95% consensus among the experts and were endorsed
      by the independent validation committee. CONCLUSION: The European Guidelines
      Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice
      guidelines that have been independently validated for the safe development and
      progression of laparoscopic liver surgery. The Southampton Guidelines have
      amalgamated the available evidence and a wealth of experts' knowledge taking in
      consideration the relevant stakeholders' opinions and complying with the
      international methodology standards.

PMID- 29064912
TI  - Letter From the Editor-November 2017.

PMID- 29064915
TI  - Financial Disclosure Appendix for "Advances in Breast Reconstruction".

PMID- 29064914
TI  - The "Advances in Breast Reconstruction" Supplement.

PMID- 29064913
TI  - The Impact of Number of Cycles of Neoadjuvant Chemotherapy on Survival of
      Patients Undergoing Interval Debulking Surgery for Stage IIIC-IV Unresectable
      Ovarian Cancer: Results From a Multi-Institutional Study.
AB  - OBJECTIVES: Neoadjuvant chemotherapy (NACT) followed by interval debulking
      surgery (IDS) may be a valuable treatment option in advanced ovarian cancer when
      primary cytoreduction is not feasible. However, a consensus on the ideal number
      of NACT cycles is still lacking. In the present investigation, we aimed to
      evaluate how number of cycles of NACT influenced patients' outcomes. METHODS:
      Data of consecutive patients undergoing NACT and IDS were retrospectively
      reviewed in 4 Italian centers, and survival outcomes were evaluated. RESULTS:
      Overall, 193 patients were included. Cycles of NACT were 3, 4, and at least 5 in
      77 (40%), 74 (38%), and 43 (22%) patients, respectively. Patients undergoing 3
      cycles experienced a similar disease-free survival (hazard ratio [HR], 1.12; 95%
      confidence interval [CI], 0.89-1.65; P = 0.20) but an improved overall survival
      (HR, 1.64; 95% CI, 1.05-2.4; P = 0.02) in comparison to patients receiving at
      least 4 cycles. Five-year overall survival was 46% and 31% for patients having 3
      and at least 4 cycles. Ten-year overall survival was 26% and 18% for patients
      having 3 and at least 4 cycles (HR, 1.70; 95% CI, 1.13-2.55; P = 0.009). Using
      multivariate analysis, we observed that only Eastern Cooperative Oncology Group
      performance status correlated with overall survival (HR, 1.76; 95% CI, 1.2-2.49;
      P = 0.001). In addition, a trend toward worse overall survival was observed for
      patients with residual disease at IDS (HR, 1.29; 95% CI, 0.98-1.70; P = 0.06) and
      patients receiving at least 4 cycles (HR, 1.76; 95% CI, 0.95-3.22; P = 0.06).
      CONCLUSION: Our data underline the potential implication of number of cycles of
      NACT before IDS. Further prospective studies are warranted to assess this
      correlation.

PMID- 29064916
TI  - Introduction to "Advances in Breast Reconstruction".

PMID- 29064918
TI  - Updated Evidence on the Oncoplastic Approach to Breast Conservation Therapy.
AB  - The oncoplastic approach to breast conservation therapy has become a useful and
      popular option for women with breast cancer who wish to preserve their breast.
      The initial driving forces were aimed at minimizing the potential for a breast
      conservation therapy deformity; however, various other benefits have been
      identified that include broadening the indications for breast conservation
      therapy in some patients and improved margin control. The various techniques can
      be categorized into glandular rearrangement techniques such as breast reductions
      usually in patients with larger breasts or flap reconstruction such as the
      latissimus dorsi muscle usually in patients with smaller breasts. As the
      acceptance continues to increase, we are starting to see more outcomes evidence
      in terms of patient satisfaction, quality of life, complications, and recurrence,
      to further support the safety and efficacy of the oncoplastic approach.

PMID- 29064917
TI  - Current Trends in Postmastectomy Breast Reconstruction.
AB  - Postmastectomy immediate breast reconstruction in the U.S. continues to
      experience an upward trend owing to heightened awareness, innovations in
      reconstructive technique, growing evidence of improved patient-reported outcomes,
      and shifts in mastectomy patterns. Women with unilateral breast cancer are
      increasingly electing to undergo contralateral prophylactic mastectomy, instead
      of unilateral mastectomy or opting for breast conservation. The ascent in
      prophylactic surgeries correlates temporally to a shift toward prosthetic methods
      of reconstruction as the most common technique. Factors associated with the
      choice for implants include younger age, quicker recovery time, along with
      documented safety and enhanced aesthetic outcomes with newer generations of
      devices. Despite advances in autologous transfer, its growth is constrained by
      the greater technical expertise required to complete microsurgical transfer and
      potential barriers such as poor relative reimbursement. The increased use of
      radiation as an adjuvant treatment for management of breast cancer has created
      additional challenges for plastic surgeons who need to consider the optimal
      timing and method of breast reconstruction to perform in these patients.

PMID- 29064919
TI  - Evolving Approaches to Tissue Expander Design and Application.
AB  - Prosthetic reconstruction utilizing a 2-stage saline tissue expander-to-implant
      procedure is the most common technique for breast reconstruction in the United
      States. For nearly the past 50 years, 2-stage breast reconstruction using saline
      tissue expanders has been the standard of care. However, in December 2016, a
      carbon dioxide-filled, remote-controlled tissue expander received U.S. Food and
      Drug Administration clearance. This tissue expander, known as the AeroForm Tissue
      Expander System (AirXpanders, Inc., Palo Alto, Calif.), is a novel, patient
      controlled, needle-free expander operated by a wireless remote control device,
      which allows patients the comfort and convenience of home expansion, precluding
      the need for percutaneous saline injections. A multicenter, randomized,
      prospective clinical trial has revealed statistically significant shorter times
      to full expansion as well as shorter overall reconstructive times. It is the
      first tissue expander device designed successfully with an alternative filling
      medium to saline, namely carbon dioxide. This CO2-filled expander thus provides
      several potential advantages over previous expander designs, including patient
      controlled expansion, obviation of saline injections, and shorter expansion
      times.

PMID- 29064920
TI  - What's New in Acellular Dermal Matrix and Soft-Tissue Support for Prosthetic
      Breast Reconstruction.
AB  - Of the nearly 90,000 implant-based breast reconstructions performed in the United
      States, the majority use internal soft-tissue support. Aesthetically, these
      constructs may allow for better positioning of prosthesis, improve lower pole
      expansion, and increase projection. They may have particular utility in direct-to
      implant, nipple-sparing mastectomies, and prepectoral reconstructions. In recent
      years, new permutations of acellular dermal matrices have evolved with diverse
      shapes, sizes, form-factor innovations, and processing characteristics. The
      literature is largely limited to retrospective studies (and meta-analyses
      thereof), making robust comparisons of 1 iteration vis-a-vis another difficult.
      Although synthetic mesh may provide a cost-effective alternative in primary and
      secondary reconstruction, comparative studies with acellular dermal matrix are
      lacking. This review aims to provide a balanced overview of recent biologic and
      synthetic mesh innovation. As this technology (and concomitant techniques)
      evolve, the reconstructive surgeon is afforded more-and better-choices to improve
      care for patients.

PMID- 29064921
TI  - Nipple-Sparing Mastectomy and Direct-to-Implant Breast Reconstruction.
AB  - Breast reconstruction following mastectomy has evolved to preserve the native
      skin and nipple of the breast and create a natural-appearing reconstruction in 1
      or 2 surgeries. Nipple-sparing procedures appear to be oncologically safe with
      low risks of cancer recurrence. In our series of 2,182 nipple-sparing
      mastectomies, there was no development or recurrence of cancer in the nipple.
      Direct-to-implant single-stage surgery offers the patient a complete
      reconstruction at the time of mastectomy. Patient selection centers on
      preoperative breast anatomy combined with postoperative goals for size and uplift
      of the breast. The best candidates for nipple-sparing mastectomy and direct-to
      implant breast reconstruction include those with grade I-II breast ptosis and
      those desiring to stay approximately the same breast size. The choice of incision
      and width of the implant play key roles in nipple centralization. Partial muscle
      coverage with acellular dermal matrix remains the most common technique to
      support the implant and offers the advantage of more soft-tissue coverage in the
      upper pole. With experience, complications and revisions are similar in this
      approach compared with more traditional 2-stage tissue expander-implant
      reconstruction. Thus, nipple-sparing mastectomy and direct-to-implant breast
      reconstruction is emerging as a preferred method of breast reconstruction when
      the breast skin envelope is sufficiently perfused.

PMID- 29064922
TI  - Prepectoral Breast Reconstruction.
AB  - Oncologic and reconstructive advancements in the management of patients with
      breast cancer and at high risk for breast cancer have led to improved outcomes
      and decreased patient morbidity. Traditional methods for prosthetic breast
      reconstructions have utilized total or partial muscle coverage of prosthetic
      devices. Although effective, placement of devices under the pectoralis major
      muscle can be associated with increased pain due to muscle spasm and animation
      deformities. Prepectoral prosthetic breast reconstruction has gained popularity
      in the plastic surgery community, and long-term outcomes have become available.
      This article will review the indications, technique, and current literature
      surrounding prepectoral prosthetic breast reconstruction.

PMID- 29064923
TI  - Breast Reconstruction and Radiation Therapy: An Update.
AB  - With the indications for radiation therapy in the treatment of breast cancer
      continuing to expand, many patients present for reconstruction having previously
      had radiation or having a high likelihood of requiring radiation following
      mastectomy. Both situations are challenging for the plastic surgeon, with
      different variables impacting the surgical outcome. To date, multiple studies
      have been performed examining prosthetic and autologous reconstruction in this
      setting. The purpose of this article was to provide a general platform for
      understanding the literature as it relates to reconstruction and radiation
      through an examination of recent systematic reviews and relevant recent
      publications. We examined this with a focus on the timing of the radiation, and
      within this context, examined the data from the traditional surgical outcomes
      standpoint as well as from a patient-reported outcomes perspective. The data
      provided within will aid in patient counseling and the informed consent process.

PMID- 29064924
TI  - Fat Grafting to the Breast: Clinical Applications and Outcomes for Reconstructive
      Surgery.
AB  - This article is a review of fat grafting for breast reconstruction. The use of
      small volume fat grafting for the correction of step-off deformities, intrinsic
      deformities, and extrinsic deformities of the breast, and the uses of large
      volume fat grafting for total breast reconstruction, correction of implant
      complications with simultaneous implant exchange with fat, and correction of
      noncancer chest wall deformities is reviewed. Cancer monitoring and the risks of
      cancer recurrence following fat-grafting to the breast is also reviewed.

PMID- 29064926
TI  - Functional Neuroimaging in Irritable Bowel Syndrome: A Brain Twister.

PMID- 29064925
TI  - Lower Extremity Free Flaps for Breast Reconstruction.
AB  - Thigh-based flaps are typically a secondary option for breast reconstruction
      because of concerns regarding limited tissue volume and donor-site morbidity. In
      recent years, there have been a number of new techniques and insights that have
      resulted in greater flexibility and improved outcomes. This article reviews
      lessons learned from a large collective experience using the following 4 flaps:
      transverse upper gracilis also known as transverse myocutaneous gracilis,
      diagonal upper gracilis, profunda artery perforator, and lateral thigh perforator
      flaps. Flap selection considerations include the patient's fat distribution and
      skin laxity, perforator anatomy, and scar location. Pearls to minimize donor-site
      morbidity include avoiding major lymphatic collectors in the femoral triangle and
      along the greater saphenous vein and respecting the limits of flap dimension to
      reduce wound healing complications and distal ischemia. Limited flap volume may
      be addressed with stacking another flap from the contralateral thigh or primary
      fat grafting as opposed to overaggressive flap harvest from a single thigh. A
      detailed review of the benefits and disadvantages of each flap and strategies to
      improve results is discussed. With careful planning and selection, thigh-based
      flaps can provide a reliable option patients desiring autologous breast
      reconstruction.

PMID- 29064927
TI  - Reduced Functional Connectivity Between the Hypothalamus and High-order Cortical
      Regions in Adolescent Patients With Irritable Bowel Syndrome.
AB  - The hypothalamus plays a critical role in maintaining visceral homeostasis.
      Altered hypothalamus activation has been implicated in functional
      gastrointestinal disorders, including irritable bowel syndrome (IBS). One
      important aspect of homeostatic regulation is the cortical modulation of limbic
      and paralimbic subsystems, including the hypothalamus, which in turn affects the
      descending regulatory processes mediating visceral homeostasis. Using
      neuroimaging, we evaluated hypothalamus functional connectivity in adolescent
      patients with IBS and age-matched healthy controls who received rectal distension
      stimulations. More extensive hypothalamus connectivity was observed in liminal
      than subliminal condition in controls, but not in patients with IBS. Compared
      with controls, patients with IBS showed significantly reduced hypothalamus
      connectivity in the bilateral prefrontal cortices, supplementary motor and
      premotor areas, bilateral sensorimotor cortex, and limbic subareas, which are
      specifically involved in homeostatic regulation. The findings support the
      generalized homeostatic regulation model that reduced cortical and limbic
      modulations of hypothalamus functioning underlies disrupted visceral homeostasis
      in patients with IBS.

PMID- 29064928
TI  - Rapid Infliximab Infusion in Children: A Multicenter Retrospective Cohort Study.
AB  - Pediatric data on rapid infliximab infusion are scarce. We report our experience
      with a 1-hour rapid infusion protocol, prescribed in 3 pediatric inflammatory
      bowel disease units during 18 to 26 months. Children treated with infliximab for
      inflammatory bowel disease using a standard 2- to 3-hour infusion protocol were
      switched to a 1-hour protocol if they had received at least 4 standard duration
      infusions with no infusion reactions, there was no recent dose increase and no
      more than 10 weeks had elapsed since the previous infusion. A total of 102
      children received infliximab infusions during the study period (85 Crohn disease;
      mean age 14.6 +/- 2.6 years) of whom 63 were switched to the rapid infusions.
      Seven patients on the rapid protocol (11%) and 6 patients on the standard
      protocol (15%) had infusion reactions (P = 0.55). Consistent with adult data, our
      study indicates that a 1-hour infliximab protocol in selected patients offers a
      safe alternative to the traditional 2- to 3-hour infusions.

PMID- 29064931
TI  - Transaminases and Pediatric Nonalcoholic Fatty Liver Disease Diagnosis.

PMID- 29064929
TI  - Highly Concentrated Preterm Formula as an Alternative to Powdered Human Milk
      Fortifier: A Randomized Controlled Trial.
AB  - OBJECTIVE: The aim of the study was to assess clinical feasibility and tolerance
      of concentrated preterm formula at 30 kcal/oz (CPF30) to fortify human milk to a
      caloric density of 24 kcal/oz, compared to conventional powdered human milk
      fortifier (PHMF). STUDY DESIGN: Very low birth weight neonates were stratified by
      birth weight and randomized to receive human milk fortification using CPF30 or
      PHMF. Infants were monitored from first introduction of human milk fortification,
      until fortified feeds were well tolerated. Primary outcome was weight gain;
      secondary outcomes included other measures of feeding intolerance (residual
      gastric aspirates, feeds held, prokinetic therapy), sepsis, and death. The
      clinical and study personnel were blinded to the intervention. RESULTS: No
      significant differences in weight gain or other measures of feeding tolerance
      were demonstrated between CPF30 and PHMF. Macronutrient intake was similar
      between both groups. Infants with a birth weight of >= 1000 g who received CPF30,
      experienced fewer days NPO (nil per os; nothing per mouth) and a trend toward
      lower incidence of NEC, compared with those who received PHMF.. The amount of
      human milk consumed was significantly lower in the CPF30 group. CONCLUSIONS: Both
      fortifiers were similarly well tolerated. Fortification of human milk with CPF30
      is a safe and feasible alternative to conventional PHMF.

PMID- 29064930
TI  - Please Do Not Forget Muscle Disease When Evaluating Elevated Transaminases.

PMID- 29064932
TI  - Screening for NAFLD in Children: Do We Know the Optimal ALT Cut-off?

PMID- 29064934
TI  - Amiodarone-induced pulmonary toxicity.
AB  - Amiodarone is widely used to prevent ventricular and supraventricular
      dysrhythmias but has a number of toxicities. One of the most devastating adverse
      reactions to this drug is pulmonary toxicity, which can present in a myriad of
      different ways. Toxicity is difficult to diagnose because many of its features
      also are seen in nontoxic patients. This article reviews the pathophysiology,
      presentation, diagnosis, and treatment of amiodarone-induced pulmonary toxicity.

PMID- 29064936
TI  - Efficiently finding and using evidence to guide clinical practice and improve
      care.
AB  - Using evidence to guide patient care improves patient outcomes. However, the
      volume of clinical and scientific literature and demands on provider time make
      staying current challenging. Primary literature searching or using public search
      engines to answer clinical questions often results in low-quality or incorrect
      answers, potentially yielding suboptimal clinical care. This article describes
      systematic strategies for primary literature searching that can yield higher
      quality results than an unstructured approach.

PMID- 29064935
TI  - Recognizing primary effort thrombosis in primary care.
AB  - Primary effort thrombosis is a noniatrogenic deep vein thrombosis of the upper
      extremity. The incidence of this condition is 1 to 2 in 100,000 per year. The
      risk factors and typical patient population differ from other thrombotic events.
      Patients with primary effort thrombosis are typically young, athletic, and lack
      comorbidities. Due to its low incidence and unique risk factors, primary effort
      thrombosis often is misdiagnosed as a musculoskeletal injury. However, early
      recognition, initial testing with Doppler ultrasound, and immediate referral to a
      vascular center is essential to achieve optimal outcomes. This article reviews
      risk factors, pathogenesis, presentation, diagnosis, and acute management of
      primary effort thrombosis for primary care providers.

PMID- 29064937
TI  - A history of US Army PAs.
AB  - The US military has a long tradition of using physician assistants (PAs). The
      Army began using PAs in 1971 in an effort to supplement the physicians and
      surgeons in the medical corps. As their numbers grew, PAs gradually replaced
      general medical officers assigned to battalions. Later, specialty positions
      developed in aviation medicine, orthopedics, and emergency medicine. The need for
      a PA serving as an adviser in the major commands slowly developed at all levels
      of leadership. In 2015, the Army removed limitations on female PAs assigned to
      combat units. PAs lead in tactical and clinical settings, filling command roles,
      senior clinical positions, and administrative leadership roles.

PMID- 29064938
TI  - Why is buprenorphine coformulated with naloxone?
AB  - Combination buprenorphine-naloxone is a cornerstone of outpatient treatment for
      substance use disorder, and is more widely accessible in primary care. Because
      oral buprenorphine has been diverted and abused for its euphoric properties, a
      combination formulation was developed and will trigger withdrawal symptoms if
      injected IV.

PMID- 29064939
TI  - Diabetic ketoacidosis.

PMID- 29064940
TI  - Pediatric forearm injury after a fall.

PMID- 29064942
TI  - What is the linear rash on this child's leg?

PMID- 29064943
TI  - Saying grace.

PMID- 29064941
TI  - Substance abuse screening in adolescents.
AB  - Substance abuse among adolescents is a significant public health challenge. This
      article reviews changes to the American Academy of Pediatrics' policy statement
      recommending the use of SBIRT (screening, brief intervention, and referral for
      treatment) to screen adolescents for substance abuse.

PMID- 29064944
TI  - I have hair.

PMID- 29064945
TI  - Triggers, part 2.

PMID- 29064946
TI  - Synthetic cannabinoids: A review of the clinical implications of a new drug of
      choice.
AB  - Synthetic marijuana use is an emerging public health problem in the United
      States, and can cause agitation, severe psychosis, bizarre hallucinations, and
      possibly death. This article describes these products, which are unregulated and
      can vary widely in composition, and how clinicians can recognize patients with
      synthetic cannabinoid toxicity and treat them appropriately to minimize morbidity
      and mortality.

PMID- 29064948
TI  - Efficacy and Acceptability of Psychotherapy for Anxious Young Children: A Meta
      analysis of Randomized Controlled Trials.
AB  - We aimed to provide an overview of psychotherapy in young anxious children (mean
      age, <7 years). Seven electronic databases, including PubMed, EMBASE, Cochrane,
      Web of Science, PsycINFO, CINAHL, and ProQuest Dissertations, were searched.
      Randomized controlled trials that compared psychotherapies with control
      conditions were included. Efficacy (score change on an anxiety rating scale and
      rate of being freed from anxiety) and acceptability (discontinuations due to any
      event) were evaluated. Six of the total seven studies included in our study
      adopted cognitive behavioral therapy (CBT), with only one adopting behavior
      therapy (BT). Psychotherapy effectively reduced anxiety symptoms (standardized
      mean difference = -0.83; 95% confidence interval [CI], -1.08 to -0.57), and its
      rate of freeing patients from anxiety was high (risk ratio [RR] = 0.30; 95% CI,
      0.19 to 0.47). No remarkable difference for acceptability was found between the
      two therapy types (RR = 0.54; 95% CI, 0.25 to 1.18). Psychotherapy, both CBT and
      BT, benefits young anxious children.

PMID- 29064951
TI  - From the Editor.

PMID- 29064952
TI  - Case in Health Care Management.

PMID- 29064950
TI  - Epidemiology of Reduced Visual Acuity among Chinese Multiethnic Students.
AB  - SIGNIFICANCE: Data regarding the epidemiology of reduced visual acuity (VA) among
      multiethnic children and adolescents in China are few. Understanding the vision
      related health inequalities among different ethnic groups is crucial for health
      resource allocations and clinical managements for eye diseases. PURPOSE: We aim
      to determine the prevalence, main causes, and health inequalities of reduced VA
      in multiethnic school students in rural China. METHODS: A school-based eye survey
      including 7681 multiethnic school students aged 5 to 16 years in the southwestern
      part of China was conducted. Detailed ocular examinations including VA
      measurements, ocular motility evaluations, bilateral postcycloplegic refractions,
      and the assessments of the external eye, anterior segment, media, and retinal
      fundus were carried out by trained research vision professionals. Visual acuity
      was measured using a logarithm of the minimum angle of resolution E-chart, and
      reduced VA was defined as a presenting VA of worse than 20/40. Concentration
      index was initiatively utilized to measure health inequalities among different
      ethnic groups. RESULTS: The prevalence of reduced VA was 11.4 per 100 children
      (95% confidence interval, 10.7 to 12.1%) based on the worse-seeing eye data. The
      prevalence of reduced VA increased with increasing age (P < .001 for trend) and
      was higher among girls compared with boys (P < .0001). Uncorrected refractive
      error was the principal cause for reduced VA, which accounted for 87.3% of the
      participants with reduced VA. The concentration index for reduced VA was 0.07
      among different ethnic groups. CONCLUSIONS: Compared with the estimates reported
      from previous studies on Chinese children and adolescents, a relatively lower
      prevalence of reduced VA was observed among multiethnic school students in rural
      China. Ethnic variations and health inequalities of reduced VA were not
      significant in this study.

PMID- 29064953
TI  - The Emperor's New Surgery.

PMID- 29064949
TI  - Metacognition Is Necessary for the Emergence of Motivation in People With
      Schizophrenia Spectrum Disorders: A Necessary Condition Analysis.
AB  - Metacognition deficits are a putative cause of reduced motivation in people with
      schizophrenia spectrum disorders. However, it is unclear whether certain levels
      of metacognition are necessary for motivation to emerge. This study used a
      Necessary Condition Analysis to test whether metacognition was necessary for the
      presence of motivation and to identify the minimum level of metacognition
      necessary for high motivation to be possible in people with schizophrenia
      spectrum disorders (N = 175). Participants completed clinician-rated measures of
      metacognition and motivation. Necessary Condition Analysis revealed that
      metacognition is a necessary condition for motivation and that high levels of
      motivation were only possible, although not guaranteed, when at least a basic
      level of metacognition was present. The findings suggest that metacognition is a
      necessary building block for the development of motivation. Results suggest that
      targeting metacognition may be essential for improving motivation among people
      with schizophrenia spectrum disorders who do not meet this metacognition
      threshold.

PMID- 29064954
TI  - MrgprA3 shows sensitization to chloroquine in an acetone-ether-water mice model.
AB  - Chronic itch, a distressing symptom of many cutaneous and systemic diseases,
      significantly impairs quality of life. However, its underlying molecular
      mechanism is still unclear. Mas-related G protein-coupled receptor A3 (MrgprA3)
      is considered an itch-specific receptor. MrgprA3 neurons are identified as a
      class of itch-specific neurons, but the role of MrgprA3 in chronic itch remains
      elusive. An acetone-ether-water (AEW) model as a histamine-independent itch model
      is often used in the study of chronic pruritus. In this study, behavioral tests,
      immunostaining, cell culture, calcium imaging, and other experiments were carried
      out to examine the expression of MrgprA3. The results showed that the scratching
      bouts induced by chloroquine increased significantly under the AEW condition; the
      density of MrgprA3 sensory fibers in the AEW-treated skin area and the number of
      MrgprA3 neurons in dorsal root ganglia from the AEW model mice also increased
      significantly. Further analysis showed that the MrgprA3 in mRNA level was also
      increased after AEW treatment. These results indicated that MrgprA3 played a
      crucial role in chronic pruritus in the AEW model.

PMID- 29064955
TI  - Modulation of short-latency afferent inhibition and short-interval intracortical
      inhibition by test stimulus intensity and motor-evoked potential amplitude.
AB  - The present study aimed to investigate the effects of changes in motor-evoked
      potential (MEP) amplitude on short-latency afferent inhibition (SAI) and short
      interval intracortical inhibition (SICI). MEPs in response to transcranial
      magnetic stimulation (TMS) of the left primary motor cortex were measured from
      the right first dorsal interosseous muscle of 10 healthy participants. SAI was
      evaluated by measuring MEPs in response to variable-intensity test TMS pulses
      delivered 22 ms following electrical stimulation of the right ulnar nerve
      (intensity fixed at the motor threshold). SICI was evaluated by pairing a
      constant conditioning TMS pulse [80% of resting motor threshold (RMT)] with a
      second variable-intensity TMS test pulse (interstimulus interval of 2 ms). The
      intensity of the test stimulus was set at 110, 115, 120, 125, or 130%RMT on a
      given trial. SAI was significantly reduced when evoked by a 125%RMT test TMS
      pulse compared with 110%RMT, and absent at 130%RMT. There was no significant
      difference in SICI at 110-130%RMT. Significant positive correlations were
      detected between the unconditioned and conditioned MEP amplitudes at both SAI and
      SICI. This study demonstrated that SAI and SICI are highly sensitive to the MEP
      amplitude and SAI decreases with increasing MEP amplitude, whereas SICI does not
      change. The different responses for SAI and SICI to the increasing MEP amplitude
      is interpreted as evidence that different inhibitory neural circuits may be
      involved in SAI and SICI.

PMID- 29064956
TI  - Patient Preferences for Outcomes After Kidney Transplantation: A Best-Worst
      Scaling Survey.
AB  - BACKGROUND: The care of kidney transplant recipients involves a balance between
      maximizing graft survival and serious adverse outcomes. This study aimed to
      quantify patients' preferences and trade-offs for important outcomes after
      transplantation. METHODS: A best-worst scaling survey, analyzed by multinomial
      logit models, was used to calculate normalized preference scores (0, best; 1,
      worst), for varying years of graft duration and risk of dying before graft
      failure, cancer, cardiovascular disease, diabetes, infection, anxiety/depression,
      diarrhoea/nausea, and weight gain. Willingness to trade years of graft survival
      to minimize the risk of adverse outcomes was calculated. RESULTS: Ninety-three
      transplant recipients from 2 Australian transplant units and an on-line panel
      (aged 18-69 years (mean time since transplantation, 7 years) completed the
      survey. Graft loss at 1 year was the least desirable outcome (mean preference
      value, 0.0:95% confidence intervals, -0.05 to 0.05) and worse than a 100% risk of
      dying before graft loss (0.17: 0.12-0.23). Graft duration of 5 years had the same
      preference scores (ie, as bad) as the maximum risk of all adverse outcomes
      including a 100% risk of dying before graft failure. To achieve zero risk of
      cancer, dying, and cardiovascular disease participants were only willing to trade
      3.1(2.1 to 4.7), 1.7(1.1 to 2.5), and 1.2(0.8 to 1.8) years of graft survival,
      respectively, and less than 1 year for all other outcomes. CONCLUSIONS:
      Transplant recipients regarded graft loss as worse than death and showed minimal
      willingness to trade a reduction in this outcome with an improvement in any other
      outcome.

PMID- 29064957
TI  - An Evaluation of the Safety and Efficacy of Simultaneous Bilateral Nephrectomy
      and Renal Transplantation for Polycystic Kidney Disease: A 20-Year Experience.
AB  - BACKGROUND: Many strategies regarding timing of native nephrectomies exist for
      patients with symptomatic polycystic kidney disease (PCKD). METHODS: This is a
      single-center, retrospective study of 594 adults with PCKD who had renal
      transplants from 1994 to 2014. Three groups were analyzed: renal transplant-only
      recipients (tx alone), recipients of simultaneous bilateral nephrectomies and
      transplant (simultaneous), and recipients with pretransplant bilateral
      nephrectomies (pre). The primary outcome was graft survival. Secondary outcomes
      included postoperative complications. RESULTS: Five hundred sixty-five adults
      with PCKD received kidney transplants (303 tx alone, 161 simultaneous, 27 pre).
      Ten-year posttransplant graft survival was 68.5%, 63.6%, and 65.7% for tx alone,
      simultaneous, and precohorts (P = 0.86). No statistically significant differences
      were observed in rates of postoperative ileus, deep vein thrombosis, small bowel
      obstruction, urinary stricture, urine leak, hernia formation, and delayed graft
      function. More wound complications were seen in prepatients (25.9% vs 11.1% tx
      alone, 5.1% simultaneous; P = 0.03), whereas simultaneous patients had a lower
      incidence of lymphocele (1.3% vs 11.1% pre, 10.2% tx-alone; P = 0.002).
      Importantly, simultaneous patients had more renal vascular thromboses (4.4% vs
      1.3% tx alone, 0% pre; P = 0.04). 16.3% of renal transplant alone patients
      required nephrectomy at 10 years follow-up. Twenty-nine patients were referred
      for transplant having had nephrectomies and were ultimately not transplanted. In
      4 of these patients who had data available for analysis, the mean panel-reactive
      antibody significantly increased after nephrectomy was performed. CONCLUSIONS:
      Simultaneous bilateral nephrectomy can be safely performed at the time of renal
      transplantation, however, carries a significantly increased risk of renal
      vascular thrombosis.

PMID- 29064958
TI  - Sildenafil Citrate Therapy for Oligohydramnios: A Randomized Controlled Trial.

PMID- 29064959
TI  - In Reply.

PMID- 29064960
TI  - Gestational Diabetes Mellitus and Frequency of Blood Glucose Monitoring: A
      Randomized Controlled Trial.

PMID- 29064964
TI  - Practice Bulletin No. 184 Summary: Vaginal Birth After Cesarean Delivery.
AB  - Trial of labor after cesarean delivery (TOLAC) refers to a planned attempt to
      deliver vaginally by a woman who has had a previous cesarean delivery, regardless
      of the outcome. This method provides women who desire a vaginal delivery the
      possibility of achieving that goal-a vaginal birth after cesarean delivery
      (VBAC). In addition to fulfilling a patient's preference for vaginal delivery, at
      an individual level, VBAC is associated with decreased maternal morbidity and a
      decreased risk of complications in future pregnancies as well as a decrease in
      the overall cesarean delivery rate at the population level (1-3). However,
      although TOLAC is appropriate for many women, several factors increase the
      likelihood of a failed trial of labor, which in turn is associated with increased
      maternal and perinatal morbidity when compared with a successful trial of labor
      (ie, VBAC) and elective repeat cesarean delivery (4-6). Therefore, assessing the
      likelihood of VBAC as well as the individual risks is important when determining
      who is an appropriate candidate for TOLAC. Thus, the purpose of this document is
      to review the risks and benefits of TOLAC in various clinical situations and to
      provide practical guidelines for counseling and management of patients who will
      attempt to give birth vaginally after a previous cesarean delivery.

PMID- 29064965
TI  - Practice Bulletin No. 185 Summary: Pelvic Organ Prolapse.
AB  - Pelvic organ prolapse (POP) is a common, benign condition in women. For many
      women it can cause vaginal bulge and pressure, voiding dysfunction, defecatory
      dysfunction, and sexual dysfunction, which may adversely affect qual-ity of life.
      Women in the United States have a 13% lifetime risk of undergoing surgery for POP
      (1). Although POP can occur in younger women, the peak incidence of POP symptoms
      is in women aged 70-79 years (2). Given the aging population in the United
      States, it is anticipated that by 2050 the number of women experiencing POP will
      increase by approximately 50% (3). The purpose of this joint document of the
      American College of Obstetricians and Gynecologists and the American
      Urogynecologic Society is to review information on the current understanding of
      POP in women and to outline guidelines for diagnosis and management that are
      consistent with the best available scientific evidence.

PMID- 29064966
TI  - Practice Bulletin No. 186 Summary: Long-Acting Reversible Contraception: Implants
      and Intrauterine Devices.
AB  - Intrauterine devices and contraceptive implants, also called long-acting
      reversible contraceptives (LARC), are the most effective reversible contraceptive
      methods. The major advantage of LARC compared with other reversible contraceptive
      methods is that they do not require ongoing effort on the part of the patient for
      long-term and effective use. In addition, after the device is removed, the return
      of fertility is rapid (1, 2). The purpose of this Practice Bulletin is to provide
      information for appropriate patient selection and evidence-based recommendations
      for LARC initiation and management. The management of clinical challenges
      associated with LARC use is beyond the scope of this document and is addressed in
      Committee Opinion No. 672, Clinical Challenges of Long-Acting Reversible
      Contraceptive Methods (3).

PMID- 29064967
TI  - Committee Opinion No. 724 Summary: Consumer Testing for Disease Risk.
AB  - With the increased emphasis on patient-driven health care and readily available
      access to patients through the internet and media, many genetic testing companies
      have begun to market directly to consumers. Direct-to-consumer genetic testing
      raises unique concerns and considerations, including limited knowledge among
      patients and health care providers of available genetic tests, difficulty in
      interpretation of genetic test results, lack of oversight of companies that offer
      genetic testing, and issues of privacy and confidentiality. When undergoing any
      direct-to-consumer genetic testing, the consumer should be apprised of risk from
      screening or susceptibility test results that can neither prove nor eliminate
      disease potential. Because ordering an appropriate genetic test and
      interpretation of genetic test results are complex, an obstetrician-gynecologist
      or other health care provider with knowledge of genetics should be involved in
      ordering and interpreting the results of any genetic test with medical
      implications. When an individual presents test results to a health care provider
      from a direct-to-consumer genomic test that putatively assesses the risk of
      specific diseases, the patient should be referred to an obstetrician-gynecologist
      or other health care provider who is skilled in risk assessment for the diseases
      of interest and interpretation of genetic testing results in the context of the
      individual's relevant medical and family history. Because of these considerations
      and in view of the fact that the interpretation of the results requires specific
      training and medical knowledge, direct-to-consumer genetic testing should be
      discouraged because of the potential harm of a misinterpreted or inaccurate
      result.

PMID- 29064968
TI  - Committee Opinion No. 725 Summary: Vaginal Seeding.
AB  - Vaginal seeding refers to the practice of inoculating a cotton gauze or a cotton
      swab with vaginal fluids to transfer the vaginal flora to the mouth, nose, or
      skin of a newborn infant. The intended purpose of vaginal seeding is to transfer
      maternal vaginal bacteria to the newborn. As the increase in the frequency of
      asthma, atopic disease, and immune disorders mirrors the increase in the rate of
      cesarean delivery, the theory of vaginal seeding is to allow for proper
      colonization of the fetal gut and, therefore, reduce the subsequent risk of
      asthma, atopic disease, and immune disorders. At this time, vaginal seeding
      should not be performed outside the context of an institutional review board
      approved research protocol until adequate data regarding the safety and benefit
      of the process become available.

PMID- 29064969
TI  - Clinical Updates in Women's Health Care Summary: Ischemic Heart Disease: Primary
      and Preventive Care Review.
AB  - Cardiovascular disease is the leading cause of death among women in the United
      States. Obstetrician-gynecologists often are the sole health care providers for
      otherwise healthy women. Therefore, they must be aware of risk factors, signs,
      and symptoms of cardiovascular disease and be prepared to recognize and treat
      this condition in patients as well as provide referrals when specialized care is
      indicated. Women with cardiac problems typically present with chest discomfort;
      however, they also are more likely than healthy women to present with other
      common symptoms, such as shortness of breath, back pain, jaw pain, or nausea and
      vomiting. This monograph, with a primary focus on ischemic heart disease (IHD),
      discusses the basic anatomy of the heart and coronary arteries; vascular biology;
      pathogenesis of atherosclerosis; and the screening, prevention, diagnosis, and
      treatment of IHD as well as the multiple risk factors associated with the
      development of IHD that contribute to both increased morbidity and mortality.

PMID- 29064970
TI  - Practice Bulletin No. 184: Vaginal Birth After Cesarean Delivery.
AB  - Trial of labor after cesarean delivery (TOLAC) refers to a planned attempt to
      deliver vaginally by a woman who has had a previous cesarean delivery, regardless
      of the outcome. This method provides women who desire a vaginal delivery the
      possibility of achieving that goal-a vaginal birth after cesarean delivery
      (VBAC). In addition to fulfilling a patient's preference for vaginal delivery, at
      an individual level, VBAC is associated with decreased maternal morbidity and a
      decreased risk of complications in future pregnancies as well as a decrease in
      the overall cesarean delivery rate at the population level (1-3). However,
      although TOLAC is appropriate for many women, several factors increase the
      likelihood of a failed trial of labor, which in turn is associated with increased
      maternal and perinatal morbidity when compared with a successful trial of labor
      (ie, VBAC) and elective repeat cesarean delivery (4-6). Therefore, assessing the
      likelihood of VBAC as well as the individual risks is important when determining
      who is an appropriate candidate for TOLAC. Thus, the purpose of this document is
      to review the risks and benefits of TOLAC in various clinical situations and to
      provide practical guidelines for counseling and management of patients who will
      attempt to give birth vaginally after a previous cesarean delivery.

PMID- 29064971
TI  - Practice Bulletin No. 185: Pelvic Organ Prolapse.
AB  - Pelvic organ prolapse (POP) is a common, benign condition in women. For many
      women it can cause vaginal bulge and pressure, voiding dysfunction, defecatory
      dysfunction, and sexual dysfunction, which may adversely affect qual-ity of life.
      Women in the United States have a 13% lifetime risk of undergoing surgery for POP
      (1). Although POP can occur in younger women, the peak incidence of POP symptoms
      is in women aged 70-79 years (2). Given the aging population in the United
      States, it is anticipated that by 2050 the number of women experiencing POP will
      increase by approximately 50% (3). The purpose of this joint document of the
      American College of Obstetricians and Gynecologists and the American
      Urogynecologic Society is to review information on the current understanding of
      POP in women and to outline guidelines for diagnosis and management that are
      consistent with the best available scientific evidence.

PMID- 29064972
TI  - Practice Bulletin No. 186: Long-Acting Reversible Contraception: Implants and
      Intrauterine Devices.
AB  - Intrauterine devices and contraceptive implants, also called long-acting
      reversible contraceptives (LARC), are the most effective reversible contraceptive
      methods. The major advantage of LARC compared with other reversible contraceptive
      methods is that they do not require ongoing effort on the part of the patient for
      long-term and effective use. In addition, after the device is removed, the return
      of fertility is rapid (1, 2). The purpose of this Practice Bulletin is to provide
      information for appropriate patient selection and evidence-based recommendations
      for LARC initiation and management. The management of clinical challenges
      associated with LARC use is beyond the scope of this document and is addressed in
      Committee Opinion No. 672, Clinical Challenges of Long-Acting Reversible
      Contraceptive Methods (3).

PMID- 29064973
TI  - Committee Opinion No. 724: Consumer Testing for Disease Risk.
AB  - With the increased emphasis on patient-driven health care and readily available
      access to patients through the internet and media, many genetic testing companies
      have begun to market directly to consumers. Direct-to-consumer genetic testing
      raises unique concerns and considerations, including limited knowledge among
      patients and health care providers of available genetic tests, difficulty in
      interpretation of genetic test results, lack of oversight of companies that offer
      genetic testing, and issues of privacy and confidentiality. When undergoing any
      direct-to-consumer genetic testing, the consumer should be apprised of risk from
      screening or susceptibility test results that can neither prove nor eliminate
      disease potential. Because ordering an appropriate genetic test and
      interpretation of genetic test results are complex, an obstetrician-gynecologist
      or other health care provider with knowledge of genetics should be involved in
      ordering and interpreting the results of any genetic test with medical
      implications. When an individual presents test results to a health care provider
      from a direct-to-consumer genomic test that putatively assesses the risk of
      specific diseases, the patient should be referred to an obstetrician-gynecologist
      or other health care provider who is skilled in risk assessment for the diseases
      of interest and interpretation of genetic testing results in the context of the
      individual's relevant medical and family history. Because of these considerations
      and in view of the fact that the interpretation of the results requires specific
      training and medical knowledge, direct-to-consumer genetic testing should be
      discouraged because of the potential harm of a misinterpreted or inaccurate
      result.

PMID- 29064974
TI  - Committee Opinion No. 725: Vaginal Seeding.
AB  - Vaginal seeding refers to the practice of inoculating a cotton gauze or a cotton
      swab with vaginal fluids to transfer the vaginal flora to the mouth, nose, or
      skin of a newborn infant. The intended purpose of vaginal seeding is to transfer
      maternal vaginal bacteria to the newborn. As the increase in the frequency of
      asthma, atopic disease, and immune disorders mirrors the increase in the rate of
      cesarean delivery, the theory of vaginal seeding is to allow for proper
      colonization of the fetal gut and, therefore, reduce the subsequent risk of
      asthma, atopic disease, and immune disorders. At this time, vaginal seeding
      should not be performed outside the context of an institutional review board
      approved research protocol until adequate data regarding the safety and benefit
      of the process become available.

PMID- 29064975
TI  - Introduction.

PMID- 29064976
TI  - Considerations When Treating Cosmetic Concerns in Men of Color.
AB  - BACKGROUND: Men of color include a diverse population encompassing individuals
      with Fitzpatrick skin Types IV through VI. Yet, there is a paucity of data
      describing the cosmetic concerns of this population. OBJECTIVE: To review the
      basic science of advantages and disadvantages of skin of color and
      pathophysiology, incidence, and treatment of disorders of cosmetic concern in men
      of color. METHODS: A MEDLINE search was performed for publications on sex and
      racial differences in basic science of skin, common disorders in men of color,
      and evidence-based treatments. RESULTS: There are intrinsic differences in skin
      and hair of darker-complexioned men, particularly in Hispanics, African
      Americans, Asians, and Afro-Caribbeans. Advantages of darker skin include
      increased photoprotection, slowed aging, and a lower incidence of skin cancer.
      However, the increased content of melanin is associated with myriad dyschromias
      including melasma and postinflammatory hyperpigmentation (PIH). Additional common
      skin conditions of concern in men of color include pseudofolliculitis barbae,
      acne keloidalis nuchae, and keloids. CONCLUSION: A skin color conscious approach
      should be administered in caring for the cosmetic concerns of men of color that
      is cognizant of differences in biology of the skin and hair, associated PIH of
      disorders, and cultural/social practices among this population.

PMID- 29064977
TI  - Commentary on Considerations When Treating Cosmetic Concerns in Men of Color.

PMID- 29064978
TI  - Aesthetic Treatment With Botulinum Toxin: Approaches Specific to Men.
AB  - BACKGROUND: Men are increasingly seeking aesthetic treatment with
      neuromodulators. OBJECTIVE: To successfully treat the male patient, it is
      imperative to understand anatomical and dosing differences from his, perhaps more
      familiar, female counterpart. CONCLUSION: After reading this review including
      male-specific botulinum toxin technique tips derived from their own practices,
      the authors hope injectors are able to approach their male patients with
      increased confidence to deliver superior outcomes.

PMID- 29064979
TI  - Commentary on Aesthetic Treatment With Botulinum Toxin.

PMID- 29064980
TI  - Hair Transplantation Controversies.
AB  - BACKGROUND: Hair transplant surgery creates consistently natural appearing
      transplanted hair for men. It is increasingly popular procedure to restore
      natural growing hair for men with hair loss. OBJECTIVE: To review some current
      controversies in hair transplant surgery. MATERIALS AND METHODS: Review of the
      English PubMed literature and specialty literature in hair transplant surgery.
      RESULTS: Some of the controversies in hair transplant surgery include appropriate
      donor harvesting technique including elliptical donor harvesting versus
      follicular unit extraction whether manual versus robotic, the role of platelet
      rich plasma and low-level light surgery in hair transplant surgery. CONCLUSION:
      Hair transplant surgery creates consistently natural appearing hair. As with all
      techniques, there are controversies regarding the optimal method for performing
      the procedure. Some of the current controversies in hair transplant surgery
      include optimal donor harvesting techniques, elliptical donor harvesting versus
      follicular unit extraction, the role of low-level light therapy and the platelet
      rich plasma therapy in the procedure. Future studies will further clarify their
      role in the procedure.

PMID- 29064981
TI  - Commentary on Chemical Peels in Men.

PMID- 29064982
TI  - Lasers and Energy-Based Devices in Men.
AB  - BACKGROUND: The demand for cosmetic treatments with lasers and energy-based
      devices has increased among men, but there is a dearth of literature that
      addresses the approach and treatment of cosmetic male patients. OBJECTIVE: To
      summarize common cosmetic concerns for which male patients seek cosmetic
      treatments and to provide sex-specific recommendations for the lasers and energy
      based devices that can be used for treatment. MATERIALS AND METHODS: The authors
      conducted a literature search using the PubMed/MEDLINE and Google Scholar
      databases using the search terms male, men, gender, and cosmetic dermatology.
      RESULTS: The authors review sex-specific treatment recommendations regarding the
      use of lasers and energy-based devices for the conditions for which men most
      commonly seek cosmetic treatment, which include photo-/actinic damage, acne
      scarring, rhinophyma, hair removal, axillary hyperhidrosis, and loose
      neck/submental skin. Cosmetic issues the authors will touch on, but whose
      approaches or considerations vary less in men compared with women, are
      hyperpigmentation, vascular lesions, and facial rejuvenation. CONCLUSION: Sex
      specific treatment approaches with lasers and energy-based devices should be used
      to best serve male cosmetic patients.

PMID- 29064983
TI  - Commentary on Lasers and Energy-Based Devices in Men.

PMID- 29064984
TI  - Commentary on Male Body Contouring.

PMID- 29064985
TI  - Optimizing Male Periorbital Rejuvenation.
AB  - BACKGROUND: Facial rejuvenation continues to be an increasing trend among males.
      The periorbital region deserves special mention given the overall differences in
      aesthetics between sexes. OBJECTIVE: To examine the aesthetics of the upper
      eyelid, lower eyelid, lateral canthus, and brow with respect to male periorbital
      rejuvenation. METHODS: The upper eyelid, lower eyelid, lateral canthus, and brow
      are examined, highlighting aesthetic differences in males and females. RESULTS:
      The authors outline principles so as to maintain a masculine appearance when
      treating the male upper eyelid, lower eyelid, lateral canthus, and brow.
      CONCLUSION: With guiding principles, the male upper lid, lower lid, brow, and
      lateral canthus can be managed to achieve optimal, consistent results.

PMID- 29064986
TI  - Male Surgical Neck Rejuvenation.
AB  - BACKGROUND: Patients who are aging, with weight gain, and increased skin laxity,
      request dermatologists to improve their neck area. Surgical and nonsurgical
      options are reviewed as well as benefits and side effects. This article will
      focus on how surgical techniques can be applied for male patients in particular.
      OBJECTIVE: To review surgical neck rejuvenation therapies available currently to
      find the best option for male patients. CONCLUSION: Surgical treatment of the
      male neck to improve mandibular contour and loose neck skin requires tightening
      of the platysmal muscle and usually skin removal in the postauricular sulcus and
      into the hairline. Most patients choose to have this performed underline
      tumescent anesthesia when given the choice of sedation versus local anesthesia.
      The other surgical variations of improving the neck contour on a male include
      using a direct excision by a midline incision starting in the submental crease
      and extending down the anterior neck. This approach allows for maximum tightening
      of the platysmal bands. The incision line can be minimized using intraoperative
      laser resurfacing immediately after suturing. Chin implants are necessary in some
      patients to give good neck improvement. The isolated neck lift is one the most
      common procedures requested by men asking for neck improvement.

PMID- 29064987
TI  - Commentary on Male Surgical Neck Rejuvenation.

PMID- 29064988
TI  - Signs of Facial Aging in Men in a Diverse, Multinational Study: Timing and
      Preventive Behaviors.
AB  - BACKGROUND: Men are a growing patient population in aesthetic medicine and are
      increasingly seeking minimally invasive cosmetic procedures. OBJECTIVE: To
      examine differences in the timing of facial aging and in the prevalence of
      preventive facial aging behaviors in men by race/ethnicity. METHODS: Men aged 18
      to 75 years in the United States, Canada, United Kingdom, and Australia rated
      their features using photonumeric rating scales for 10 facial aging
      characteristics. Impact of race/ethnicity (Caucasian, black, Asian, Hispanic) on
      severity of each feature was assessed. Subjects also reported the frequency of
      dermatologic facial product use. RESULTS: The study included 819 men. Glabellar
      lines, crow's feet lines, and nasolabial folds showed the greatest change with
      age. Caucasian men reported more severe signs of aging and earlier onset, by 10
      to 20 years, compared with Asian, Hispanic, and, particularly, black men. In all
      racial/ethnic groups, most men did not regularly engage in basic, antiaging
      preventive behaviors, such as use of sunscreen. CONCLUSION: Findings from this
      study conducted in a globally diverse sample may guide clinical discussions with
      men about the prevention and treatment of signs of facial aging, to help men of
      all races/ethnicities achieve their desired aesthetic outcomes.

PMID- 29064989
TI  - Commentary on Signs of Facial Aging in Men in a Diverse, Multinational Study:
      Timing and Preventive Behaviors.

PMID- 29064992
TI  - Developing Programs That Will Change Health Professions Education and Practice:
      Principles of Program Evaluation Scholarship.

PMID- 29064990
TI  - Commentary on ATX-101 (Deoxycholic Acid Injection) Treatment in Men.

PMID- 29064991
TI  - Efficacy of IncobotulinumtoxinA for the Treatment of Glabellar Frown Lines in
      Male Subjects: Post-Hoc Analyses From Randomized, Double-Blind Pivotal Studies.
AB  - BACKGROUND: Males are increasingly seeking minimally invasive cosmetic procedures
      such as botulinum toxin injection. However, few studies have specifically
      examined the efficacy of such procedures among men. OBJECTIVE: To assess the
      efficacy of incobotulinumtoxinA for treating glabellar frown lines (GFLs) in men.
      METHODS: Three incobotulinumtoxinA studies were included in post hoc analyses of
      responder rates: 2 pivotal Phase 3 US registration studies for GFLs (n = 55 males
      in a pooled analysis) and a European pivotal Phase 3 study for upper facial lines
      (UFLs; n = 21 males). RESULTS: In the pooled analysis of Phase 3 GFL studies,
      55.9% of males and 81.4% of females were responders on the Facial Wrinkle Scale
      (FWS) at 30 days. Similarly, 54.5% and 88.0% of males and females, respectively,
      treated for GFLs in the upper facial line study were responders on the Merz
      Aesthetics Scales (MAS) at 30 days. Lower proportions of male responders on the
      Facial Wrinkle Scale /Merz Aesthetics Scales were consistent with results from
      onabotulinumtoxinA and abobotulinumtoxinA GFL studies. CONCLUSION: Compared with
      females, males demonstrate lower response rates on wrinkle severity scales in
      studies on all 3 available botulinum toxins. Variations in treatment response are
      potentially associated with key male anatomic differences (e.g., muscle mass).
      Results emphasize the need for customized treatment plans.

PMID- 29064993
TI  - New Conversations: Justice, Disparities, and Meeting the Needs of Our Most
      Vulnerable Populations.

PMID- 29064994
TI  - Fostering Medical Student Activism With the Urban (and Rural) Poor.

PMID- 29064995
TI  - In Reply to George.

PMID- 29064996
TI  - Reflecting on Resident Attitudes About Quality Improvement.

PMID- 29064997
TI  - In Reply to Sampson et al.

PMID- 29064998
TI  - Unmatched U.S. Seniors and Residency Placement Fever.

PMID- 29064999
TI  - Educators Must Act Now to Protect Students in This Year's Match.

PMID- 29065000
TI  - A Proactive Approach for Improving Wellness Among Learners.

PMID- 29065001
TI  - Artist's Statement: Splitting.

PMID- 29065003
TI  - Commentary on A Matter of Opinion.

PMID- 29065002
TI  - A Matter of Opinion.

PMID- 29065004
TI  - 2017 Hope Babette Tang Humanism in Healthcare Essay Contest: Second Place: A
      Common Humanity We All Share.

PMID- 29065005
TI  - Finding Mary at Home: Learning Through House Calls.

PMID- 29065006
TI  - How Emotions Are Like Asbestos.

PMID- 29065007
TI  - A Fond and Grateful Farewell to JTI.

PMID- 29065008
TI  - Innovative Cardiac Devices on Chest Imaging: An Update.
AB  - Over the past decade, a rapidly increasing number of new cardiac devices have
      been created. Remaining current with these devices and how they appear on chest
      radiographs and other modalities used in chest imaging can be a challenge for the
      interpreting radiologist. This review is provides a concise summary of various
      common cardiac devices as well as recently developed devices that will be
      increasing in frequency over the coming years.

PMID- 29065010
TI  - INTRARETINAL HYPERREFLECTIVE FOCI IN BEST VITELLIFORM MACULAR DYSTROPHY.
AB  - PURPOSE: To report on the presence of hyperreflective foci (HF) on spectral
      domain optical coherence tomography in patients with Best vitelliform macular
      dystrophy (BVMD), and to describe the relationship between HF and stages of the
      disease. METHODS: Consecutive patients diagnosed with BVMD were enrolled in a
      prospective cross-sectional study. All patients and control subjects underwent a
      complete ophthalmologic examination, including best-corrected visual acuity and
      spectral domain optical coherence tomography. MAIN OUTCOME MEASURE:
      identification of HF in BVMD. Secondary outcome: assessment of the HF in each
      stage and correlation with best-corrected visual acuity. RESULTS: Overall, 75
      eyes of 39 patients were included in the study (Stage 1: 13%, Stage 2: 43%, Stage
      3: 15%, Stage 4: 21%, and Stage 5: 8%). On spectral domain optical coherence
      tomography assessment, intraretinal HF were present in 83% of all eyes, in 91% of
      eyes affected by clinical BVMD (Stages 2-5) and in 100% of patients in Stages 4
      and 5. In 46% of clinically diseased eyes, HF were localized in the fovea and in
      correspondence with the BVMD lesions at the level of the outer nuclear layer and
      outer plexiform layer. Hyperreflective foci were present in 16% of control eyes.
      Mean number of HF in eyes affected by clinical BVMD stood at 7.67 +/- 7.35. These
      were predominantly small HF (6.23 +/- 6.14, P < 0.001) localized in the outer
      nuclear layer (5.19 +/- 5.38, P = 0.001) and presented largely in the
      extrafoveal, rather than the foveal area (5.21 +/- 5.57 vs 2.46 +/- 2.73, P =
      0.001). Analysis of HF distribution revealed that the control group and Stage 1
      eyes had the fewest HF; Stage 4 displayed a significant increase in the number of
      HF compared with Stages 2 and 3; Stage 5 also showed an increased number of HF,
      although this difference was statistically significant only with Stage 3 eyes.
      The best-corrected visual acuity was negatively related to the number of HF, with
      best-corrected visual acuity deteriorating as the number of HF increased in
      Stages 2 to 5 (P < 0.001). CONCLUSION: This study describes the presence of HF in
      BVMD using spectral domain optical coherence tomography. Our data suggest that HF
      identification is correlated with the progression of the disease and could
      represent a useful biomarker of BVMD.

PMID- 29065009
TI  - Complications After Stent Placement for Aortic Coarctation: A Pictorial Essay of
      Computed Tomographic Angiography.
AB  - Stent placement is commonly used to treat aortic coarctation. Although invasive
      angiography remains the gold standard, follow-up is often performed using
      computed tomography, which allows rapid, noninvasive assessment of the aorta and
      surrounding tissues. The goal of this pictorial essay is to provide a guide to
      the interpretation of these examinations. Normal and abnormal computed
      tomographic appearance of different stent types is shown along with
      reconstructions that can help assess stent integrity and the stent position in
      relation to the aortic wall and branches. Furthermore, imaging findings of
      complications including aortic wall injuries, restenosis, and intimal hyperplasia
      are depicted.

PMID- 29065011
TI  - CORRELATION BETWEEN INNER-RETINAL CHANGES AND OUTER-RETINAL DAMAGE IN PATIENTS
      WITH IDIOPATHIC EPIRETINAL MEMBRANE.
AB  - PURPOSE: To investigate correlations between the inner-retinal irregularity index
      and interdigitation zone (IZ) defects preidiopathic and postidiopathic epiretinal
      membrane (ERM) surgery. METHODS: The authors retrospectively assessed ophthalmic
      parameters in 89 eyes of 89 patients with ERM. They divided patients into the no
      IZ defect (51, 57%) and IZ defect (38, 43%) groups. The IZ defect group was
      subdivided into recovered (22, 58%) and remaining IZ defect (16, 42%) subgroups,
      according to IZ recovery status at final examination. The inner-retinal
      irregularity index of each group was measured before and 1-, 3-, and 6-month
      postsurgery. RESULTS: Clinical characteristics were similar in both groups. The
      IZ defect group had a statistically significant higher inner-retinal irregularity
      index than the no-IZ defect group before (P = 0.023), but not after ERM surgery.
      The inner-retinal irregularity index of the recovered and remaining IZ defect
      subgroups was similar before surgery, but differed markedly 6 months after
      surgery (P = 0.048). Changes in the inner-retinal irregularity index
      quantitatively correlated with IZ defect size before and after ERM surgery (P <
      0.001). CONCLUSION: The inner-retinal irregularity index differed significantly
      according to the IZ status and also correlated with the IZ defect before and
      after ERM surgery. The inner-retinal irregularity index may reflect the outer
      retinal damage in ERM.

PMID- 29065012
TI  - PREFERRED RETINAL LOCUS LOCATIONS IN AGE-RELATED MACULAR DEGENERATION.
AB  - PURPOSE: An evaluation of the preferred retinal locus (PRL) in patients with age
      related macular degeneration and a central scotoma is becoming a standard of care
      in the practice of low-vision rehabilitation. This is a retrospective study of
      PRL specifications and whether they have a correlation with the best-corrected
      visual acuities of patients with age-related macular degeneration. METHODS:
      Seventy-two patients with macular degeneration (144 eyes) were included in the
      study. The PRLs were evaluated monocularly with a scanning laser ophthalmoscope.
      Each PRL's location, the fovea-PRL distance, the PRL edge of the lesion distance,
      and PRL stability were measured with the built-in caliper of the ophthalmoscope.
      RESULTS: The most frequent location of a PRL was nasal (29.2%). The PRL was
      located in the left visual field of 34.0% of the patients. The best-corrected
      visual acuity values were positively correlated with the lesion's vertical and
      horizontal dimensions, as well as its surface area, the PRL-fovea distance, the
      PRL border of the lesion distance, and PRL stability. CONCLUSION: The clinical
      PRL evaluation methodology that we describe can be used to facilitate making
      decisions on how to provide best visual rehabilitation to patients with a central
      scotoma.

PMID- 29065013
TI  - YOUNGER AGE AT PRESENTATION IN CHILDREN WITH COATS DISEASE IS ASSOCIATED WITH
      MORE ADVANCED STAGE AND WORSE VISUAL PROGNOSIS: A Retrospective Study.
AB  - PURPOSE: To determine the age distribution of children with Coats disease and the
      impact of age at diagnosis on the visual prognosis. METHODS: Consecutive Coats
      disease cases aged 18 years or younger at diagnosis were retrospectively
      included. Clinical and imaging parameters were analyzed by comparative,
      correlation, survival, univariate, and multivariate statistics. RESULTS: Ninety
      eight patients were included. At diagnosis, mean age was 5.4 years +/- 4.3 years
      (1 month-18 years). Younger age at diagnosis was correlated with more severe
      disease stage (P < 0.0001, r = -0.52), which was confirmed by survival analysis
      (P < 0.0001). Comparative analysis was performed between patients younger and
      older than 4 years at diagnosis. Leukocoria or strabismus was more frequent at
      presentation in patients younger than 4 years (P < 0.0001). Areas of peripheral
      nonperfusion and peripheral telangiectasia were more extensive at presentation in
      younger than older patients (P = 0.0003 and P = 0.039). Foveal sparing at
      diagnosis was less frequent in younger than older patients (2% vs. 23%, P =
      0.002). The incidence of structural complications or enucleation during follow-up
      (mean duration: 5.9 years +/- 4.5 years) was higher, and last-recorded visual
      acuity was lower in younger than older patients (P = 0.001 and P = 0.0009). Final
      logarithm of the minimal angle of resolution visual acuity was negatively
      correlated with age at diagnosis (P = 0.001, Spearman r = -0.42). Multivariate
      analysis indicated that disease stage (P < 0.0001), but not age at diagnosis (P =
      0.07), independently influenced the last-recorded visual acuity. CONCLUSION:
      Onset of Coats disease in children of younger age is associated with more severe
      manifestations, more advanced stage, and worse visual outcome. Age, correlated
      with disease stage, should be considered a prognostic marker in Coats disease.

PMID- 29065014
TI  - INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE FOR TREATMENT OF MACULAR HOLE
      RETINAL DETACHMENT IN HIGHLY MYOPIC EYES.
AB  - PURPOSE: To compare the efficacy of vitrectomy with inverted internal limiting
      membrane (ILM) flap to complete removal of the ILM for the treatment of macular
      hole (MH) retinal detachment in highly myopic eyes. METHODS: Pars plana
      vitrectomy with inverted ILM flap technique (16 eyes; inverted group) or with the
      complete removal of the ILM (16 eyes; removed group) was performed in patients
      with high myopia with MH retinal detachment. The rate of retinal reattachment and
      MH closure, the best-corrected visual acuities, and the integrity of the foveal
      microstructures in the optical coherence tomographic images were compared.
      RESULTS: Thirteen eyes (81%) in the inverted group and 15 eyes (93%) in the
      removed group had retinal reattachment after the initial surgery (P = 0.30). The
      MH was closed significantly more often in the inverted group (75%) than in the
      removed group (25%; P = 0.006). The postoperative best-corrected visual acuity
      was significantly better in the inverted group (P = 0.04). The number of eyes
      with outer nuclear layer, external limiting membrane, and ellipsoid zone lines at
      the closed MH was not significantly different in the two groups. CONCLUSION: The
      inverted ILM flap technique with the presence of bridging tissue over the MH is
      effective in closing the MH and improving the postoperative best-corrected visual
      acuity in eyes with MH retinal detachment by bridging tissue over the MH.

PMID- 29065015
TI  - Foreword: Sticks and Stones: Moving Toward a More Productive Peer-Review Process
      for Authors and Reviewers.

PMID- 29065016
TI  - Commentary: Racism and Bias in Health Professions Education: How Educators,
      Faculty Developers, and Researchers Can Make a Difference.
AB  - The Research in Medical Education (RIME) Program Planning Committee is committed
      to advancing scholarship in and promoting dialogue about the critical issues of
      racism and bias in health professions education (HPE). From the call for studies
      focused on underrepresented learners and faculty in medicine to the invited 2016
      RIME plenary address by Dr. Camara Jones, the committee strongly believes that
      dismantling racism is critical to the future of HPE.The evidence is glaring:
      Dramatic racial and ethnic health disparities persist in the United States,
      people of color remain deeply underrepresented in medical school and academic
      health systems as faculty, learner experiences across the medical education
      continuum are fraught with bias, and current approaches to teaching perpetuate
      stereotypes and insufficiently challenge structural inequities. To achieve racial
      justice in HPE, academic medicine must commit to leveraging positions of
      influence and contributing from these positions. In this Commentary, the authors
      consider three roles (educator, faculty developer, and researcher) represented by
      the community of scholars and pose potential research questions as well as
      suggestions for advancing educational research relevant to eliminating racism and
      bias in HPE.

PMID- 29065017
TI  - Summary: Research Diseases Need Holistic Care.

PMID- 29065018
TI  - Validity Evidence and Scoring Guidelines for Standardized Patient Encounters and
      Patient Notes From a Multisite Study of Clinical Performance Examinations in
      Seven Medical Schools.
AB  - PURPOSE: To examine validity evidence of local graduation competency examination
      scores from seven medical schools using shared cases and to provide rater
      training protocols and guidelines for scoring patient notes (PNs). METHOD:
      Between May and August 2016, clinical cases were developed, shared, and
      administered across seven medical schools (990 students participated). Raters
      were calibrated using training protocols, and guidelines were developed
      collaboratively across sites to standardize scoring. Data included scores from
      standardized patient encounters for history taking, physical examination, and
      PNs. Descriptive statistics were used to examine scores from the different
      assessment components. Generalizability studies (G-studies) using variance
      components were conducted to estimate reliability for composite scores. RESULTS:
      Validity evidence was collected for response process (rater perception), internal
      structure (variance components, reliability), relations to other variables
      (interassessment correlations), and consequences (composite score). Student
      performance varied by case and task. In the PNs, justification of differential
      diagnosis was the most discriminating task. G-studies showed that schools
      accounted for less than 1% of total variance; however, for the PNs, there were
      differences in scores for varying cases and tasks across schools, indicating a
      school effect. Composite score reliability was maximized when the PN was weighted
      between 30% and 40%. Raters preferred using case-specific scoring guidelines with
      clear point-scoring systems. CONCLUSIONS: This multisite study presents validity
      evidence for PN scores based on scoring rubric and case-specific scoring
      guidelines that offer rigor and feedback for learners. Variability in PN scores
      across participating sites may signal different approaches to teaching clinical
      reasoning among medical schools.

PMID- 29065019
TI  - Formative Assessment in an Integrated Curriculum: Identifying At-Risk Students
      for Poor Performance on USMLE Step 1 Using NBME Custom Exam Questions.
AB  - PURPOSE: The Hofstra Northwell School of Medicine (HNSOM) uses an essay-based
      assessment system. Recognizing the emphasis graduate medical education places on
      the United States Medical Licensing Examination (USMLE) Step exams, the authors
      developed a method to predict students at risk for lower performance on USMLE
      Step 1. METHOD: Beginning with the inaugural class (2015), HNSOM administered
      National Board of Medical Examiners (NBME) Customized Assessment Service (CAS)
      examinations as formative assessment at the end of each integrated course in the
      first two years of medical school. Using preadmission data, the first two courses
      in the educational program, and NBME score deviation from the national test
      takers' mean, a statistical model was built to predict students who scored below
      the Step 1 national mean. RESULTS: A regression equation using the highest
      Medical College Admission Test (MCAT) score and NBME score deviation predicted
      student Step 1 scores. The MCAT alone accounted for 21% of the variance. Adding
      the NBME score deviation from the first and second courses increased the variance
      to 40% and 50%, respectively. Adding NBME exams from later courses increased the
      variance to 52% and 64% by the end of years one and two, respectively. Cross
      validation demonstrated the model successfully predicted 63% of at-risk students
      by the end of the fifth month of medical school. CONCLUSIONS: The model
      identified students at risk for lower performance on Step 1 using the NBME CAS.
      This model is applicable to schools reforming their curriculum delivery and
      assessment programs toward an integrated model.

PMID- 29065020
TI  - Personalized Video Feedback and Repeated Task Practice Improve Laparoscopic Knot
      Tying Skills: Two Controlled Trials.
AB  - PURPOSE: Compare the effect of personalized feedback (PF) vs. task demonstration
      (TD), both delivered via video, on laparoscopic knot-tying skills and perceived
      workload; and evaluate the effect of repeated practice. METHOD: General surgery
      interns and research fellows completed four repetitions of a simulated
      laparoscopic knot-tying task at one-month intervals. Midway between repetitions,
      participants received via e-mail either a TD video (demonstration by an expert)
      or a PF video (video of their own performance with voiceover from a blinded
      senior surgeon). Each participant received at least one video per format, with
      sequence randomly assigned. Outcomes included performance scores and NASA Task
      Load Index (NASA-TLX) scores. To evaluate the effectiveness of repeated practice,
      scores from these trainees on a separate delayed retention test were compared
      against historical controls who did not have scheduled repetitions. RESULTS:
      Twenty-one trainees completed the randomized study. Mean change in performance
      scores was significantly greater for those receiving PF (difference = 23.1 of 150
      [95% confidence interval (CI): 0, 46.2], P = .05). Perceived workload was also
      significantly reduced (difference = -3.0 of 20 [95% CI: -5.8, -0.3], P = .04).
      Compared with historical controls (N = 93), the 21 with scheduled repeated
      practice had higher scores on the laparoscopic knot-tying assessment two weeks
      after the final repetition (difference = 1.5 of 10 [95% CI: 0.2, 2.8], P = .02).
      CONCLUSIONS: Personalized video feedback improves trainees' procedural
      performance and perceived workload compared with a task demonstration video.
      Brief monthly practice sessions support skill acquisition and retention.

PMID- 29065021
TI  - Quantitative and Qualitative Analysis of the Impact of Adoption of a Mobile
      Application for the Assessment of Professionalism in Medical Trainees.
AB  - PURPOSE: Capturing either lapses or excellence in behaviors related to medical
      professionalism is difficult. The authors report a mixed-methods analysis of a
      novel mobile platform for assessing medical professionalism in a training
      environment. METHOD: A mobile Web-based platform to facilitate professionalism
      assessment in a situated clinical setting (Professional Mobile Monitoring of
      Behaviors [PROMOBES]) was developed. A professionalism framework consisting of
      six domains (reliability, adaptability, peer relationships, upholding principles,
      team relationships, and scholarship) encompassing 25 subelements underpins the
      reporting structure. This pilot study involved 26 faculty supervising 93 medical
      trainees at two sites from January 12 to August 8, 2016. Notable professionalism
      behaviors were linked to the framework domains and elements; narrative details
      about incidences were captured on mobile devices. Surveys gauged the
      technological functionality and impact of PROMOBES on faculty assessment of
      professionalism. Qualitative focus groups were employed to elucidate user
      experience. RESULTS: Although users anticipated PROMOBES's utility would be for
      reporting lapses in professionalism, 94.7% of reports were for commendation.
      Comfort assessing professionalism (P = .04) and recognition of the reporting
      procedures for professionalism-related concerns (P = .01) improved. PROMOBES
      attained high acceptance ratings. Focus group analysis revealed that the explicit
      connection to the professionalism framework was powerful; similarly, the near
      real-time reporting capability, multiple observer inputs, and positive feedback
      facilitation were strengths. CONCLUSIONS: Making the professionalism framework
      visible and accessible via a mobile platform significantly strengthens faculty
      knowledge and behaviors regarding assessment. The strong desire to capture
      positive behaviors was an unexpected finding.

PMID- 29065022
TI  - A Randomized Cohort Study of Diagnostic and Therapeutic Thresholds in Medical
      Student Clinical Reasoning.
AB  - PURPOSE: Learning to make decisions under uncertain conditions is a critical
      component of diagnostic and therapeutic reasoning. This study sought to determine
      treatment decisions medical students make when presented with different
      thresholds of diagnostic uncertainty and whether they appropriately adjust
      diagnostic probabilities with test information. METHOD: Two classes (2015, 2016)
      of fourth-year students (N = 342) were presented a patient with viral pneumonia
      and given 10%, 20%, or 50% pretest probabilities of that patient having a
      superimposed bacterial infection. Students decided to not treat, order a
      diagnostic test to guide management, or treat without testing based on these
      probabilities. The 2015 class was provided a posttest probability of 10% or 50%
      and asked to adjust their initial treatment decision. RESULTS: When given a low
      (10%) pretest probability, students were less likely to decide to treat (6%) and
      more likely to decide not to treat (36%). The percentage of students deciding to
      treat increased as the pretest probability of a superimposed infection increased
      from 10% to 50%, while the percentage of students not wanting to treat decreased.
      Interestingly, at 10%, 20%, and 50% pretest probability levels, most students
      were unable to decide and chose to order another test (57%, 67%, and 64%,
      respectively). When provided low and high posttest probabilities, students
      appropriately adjusted their decision making, but 29% to 32% still wanted
      additional testing. CONCLUSIONS: Students adjusted treatment decisions to reflect
      different levels of diagnostic uncertainty, but varied considerably in their
      individual thresholds to make decisions, possibly contributing to unnecessary
      testing.

PMID- 29065023
TI  - "You Have to Know the End of the Story": Motivations to Follow Up After
      Transitions of Clinical Responsibility.
AB  - PURPOSE: Physicians routinely transition responsibility for patient care to other
      physicians. When transitions of responsibility occur before the clinical outcome
      is known, physicians may lose opportunities to learn from the consequences of
      their decision making. Sometimes curiosity about patients does not end with the
      transition and physicians continue to follow them. This study explores
      physicians' motivations to follow up after transitioning responsibilities.
      METHOD: Using a constructivist grounded theory approach, the authors conducted 18
      semistructured interviews in 2016 with internal medicine hospitalist and resident
      physicians at a single tertiary care academic medical center. Constant
      comparative methods guided the qualitative analysis, using motivation theories as
      sensitizing constructs. RESULTS: The authors identified themes that characterized
      participants' motivations to follow up. Curiosity about patients' outcomes
      determined whether or not follow-up occurred. Insufficient curiosity about
      predictable clinical problems resulted in the choice to forgo follow-up.
      Sufficient curiosity due to clinical uncertainty, personal attachment to
      patients, and/or concern for patient vulnerability motivated follow-up to fulfill
      goals of knowledge building and professionalism. The authors interpret these
      findings through the lenses of expectancy-value (EVT) and self-determination
      (SDT) theories of motivation. CONCLUSIONS: Participants' curiosity about what
      happened to their patients motivated them to follow up. EVT may explain how
      participants made choices in time-pressured work settings. SDT may help interpret
      how follow-up fulfills needs of relatedness. These findings add to a growing body
      of literature endorsing learning environments that consider task-value trade-offs
      and support basic psychological needs of autonomy, competency, and relatedness to
      motivate learning.

PMID- 29065024
TI  - Learning From Patients: Why Continuity Matters.
AB  - PURPOSE: Patient continuity, described as the student participating in the
      provision of comprehensive care of patients over time, may offer particular
      opportunities for student learning. The aim of this study was to describe how
      students experience patient continuity and what they learn from it. METHOD: An
      interpretive phenomenological study was conducted between 2015 and 2016.
      Seventeen fourth-year medical students were interviewed following a longitudinal
      clinical placement and asked to describe their experiences of patient continuity
      and what they learned from each experience. Transcripts were analyzed by
      iteratively refining and testing codes, using health system definitions of
      patient continuity as sensitizing concepts to develop descriptive themes.
      RESULTS: Students described three different forms of patient continuity.
      Continuity of care, or relational continuity, enabled students to build trusting
      and professional relationships with their patients. Geographical continuity
      allowed students to access information about patients from electronic records and
      their preceptors which allowed students to achieve diagnostic closure and learn
      to reevaluate their decisions. Students valued the learning that accrued from
      following challenging patients and addressing challenging decisions over time.
      Although difficult, these patient continuity experiences led students to critical
      reflection that was both iterative and deep, leading to intentions for future
      behavior. CONCLUSIONS: Patient continuity in medical education does not depend
      solely on face-to-face continuity. Within various patient continuity experiences,
      following challenging patients and experiencing unanticipated diagnostic and
      management outcomes trigger critical reflection in students, leading to deep
      learning.

PMID- 29065025
TI  - How and Why Preclerkship Students Set Learning Goals and Assess Their
      Achievement: A Qualitative Exploration.
AB  - PURPOSE: Health professionals are expected to routinely assess their weaknesses,
      set learning goals, and monitor their achievement. Unfortunately, it is well
      known that these professionals often struggle with effectively integrating
      external data and self-perceptions. To know how best to intervene, it is critical
      that the health professionals community understand the cues students and
      practitioners use to assess their abilities. Here the authors aimed to gain
      insights into how and why medical students set learning goals, monitor their
      progress, and demonstrate their learning. METHOD: In 2012, the authors conducted
      semistructured interviews with Year 2 students (n = 20), applying an inductive
      approach to data analysis by iteratively developing, refining, and testing coding
      structures. RESULTS: Themes were constructed through discussion and consensus:
      (1) Students were diverse in how they set learning goals, (2) they used a range
      of approaches to monitor their progress, and (3) they struggled to balance
      studying for exams with preparation for clinical training. Tensions observed
      highlight assumptions embedded in medical curricula that can be problematic.
      CONCLUSIONS: Educators often treat medical students as a cohesive whole, thereby
      creating a mismatch between assessments that are intended to be formative and
      information students use to monitor their progress. Despite limited exposure to
      clinical contexts, goal generation and monitoring often stem from a desire to
      prepare for clinical practice. In grappling with these tensions, it is important
      to be mindful that students are individualistic in how they balance their
      commitment to prepare for clinical work and the need to concentrate on exams.

PMID- 29065026
TI  - Study Behaviors and USMLE Step 1 Performance: Implications of a Student Self
      Directed Parallel Curriculum.
AB  - PURPOSE: To determine medical students' study behaviors when preparing for the
      United States Medical Licensing Examination (USMLE) Step 1, and how these
      behaviors are associated with Step 1 scores when controlling for likely
      covariates. METHOD: The authors distributed a study-behaviors survey in 2014 and
      2015 at their institution to two cohorts of medical students who had recently
      taken Step 1. Demographic and academic data were linked to responses. Descriptive
      statistics, bivariate correlations, and multiple linear regression analyses were
      performed. RESULTS: Of 332 medical students, 274 (82.5%) participated. Most
      students (n = 211; 77.0%) began studying for Step 1 during their preclinical
      curriculum, increasing their intensity during a protected study period during
      which they averaged 11.0 hours studying per day (standard deviation [SD] 2.1)
      over a period of 35.3 days (SD 6.2). Students used numerous third-party
      resources, including reading an exam-specific 700-page review book on average 2.1
      times (SD 0.8) and completing an average of 3,597 practice multiple-choice
      questions (SD 1,611). Initiating study prior to the designated study period,
      increased review book usage, and attempting more practice questions were all
      associated with higher Step 1 scores, even when controlling for Medical College
      Admission Test scores, preclinical exam performance, and self-identified score
      goal (adjusted R = 0.56, P < .001). CONCLUSIONS: Medical students at one public
      institution engaged in a self-directed, "parallel" Step 1 curriculum using third
      party study resources. Several study behaviors were associated with improved
      USMLE Step 1 performance, informing both institutional- and student-directed
      preparation for this high-stakes exam.

PMID- 29065027
TI  - Reflective Practice in the Clinical Setting: A Multi-Institutional Qualitative
      Study of Pediatric Faculty and Residents.
AB  - PURPOSE: To explore when and in what form pediatric faculty and residents
      practice reflection. METHOD: From February to June 2015, the authors conducted
      focus groups of pediatric faculty and residents at the University of California,
      Davis; Stanford University; and the University of California, San Francisco,
      until thematic saturation occurred. Transcripts were analyzed based on Mezirow's
      and Schon's models of reflection, using the constant comparative method
      associated with grounded theory. Two investigators independently coded
      transcripts and reconciled codes to develop themes. All investigators reviewed
      the codes and developed a final list of themes through consensus. Through
      iterative discussions, investigators developed a conceptual model of reflection
      in the clinical setting. RESULTS: Seventeen faculty and 20 residents from three
      institutions participated in six focus groups. Five themes emerged: triggers of
      reflection, intrinsic factors, extrinsic factors, timing, and outcome of
      reflection. Various triggers led to reflection; whether a specific trigger led to
      reflection depended on intrinsic and extrinsic factors. When reflection occurred,
      it happened in action or on action. Under optimal conditions, this reflection was
      goal and action directed and became critical reflection. In other instances, this
      process resulted in unproductive rumination or acted as an emotional release or
      supportive therapy. CONCLUSIONS: Participants reflected in clinical settings, but
      did not always explicitly identify it as reflection or reflect in growth
      promoting ways. Strategies to enhance critical reflection include developing
      knowledge and skills in reflection, providing performance data to inform
      reflection, creating time and space for safe reflection, and providing mentorship
      to guide the process.

PMID- 29065029
TI  - Medical Education to Enhance Critical Consciousness: Facilitators' Experiences.
AB  - PURPOSE: To analyze educators' experiences of facilitating cultural discussions
      in two global health professions education programs and what these experiences
      had taught them about critical consciousness. METHOD: A multicultural research
      team conducted in-depth interviews with 16 faculty who had extensive experience
      facilitating cultural discussions. They analyzed transcripts of the interviews
      thematically, drawing sensitizing insights from Gramsci's theory of cultural
      hegemony. Collaboration and conversation helped the team self-consciously examine
      their positions toward the data set and be critically reflexive. RESULTS:
      Participant faculty used their prior experience facilitating cultural discussions
      to create a "safe space" in which learners could develop critical consciousness.
      During multicultural interactions they recognized and explicitly addressed issues
      related to power differentials, racism, implicit bias, and gender bias. They
      noted the need to be "facile in attending to pain" as learners brought up
      traumatic experiences and other sensitive issues including racism and the impact
      of power dynamics. They built relationships with learners by juxtaposing and
      exploring the sometimes-conflicting norms of different cultures. Participants
      were reflective about their own understanding and tendency to be biased. They
      aimed to break free of such biases while role modeling how to have the courage to
      speak up. CONCLUSIONS: Experience had given facilitators in multicultural
      programs an understanding of their responsibility to promote critical
      consciousness and social justice. How faculty without prior experience or
      expertise could develop those values and skills is a topic for future research.

PMID- 29065028
TI  - A Multilevel Analysis of Professional Conflicts in Health Care Teams: Insight for
      Future Training.
AB  - PURPOSE: Without a proper understanding of conflict between health care
      professionals, designing effective conflict management training programs for
      trainees that reflect the complexity of the clinical working environment is
      difficult. To better inform the development of conflict management training, this
      study sought to explore health care professionals' experiences of conflicts and
      their characteristics. METHOD: Between 2014 and early 2016, 82 semistructured
      interviews were conducted with health care professionals directly involved in
      first-line patient care in four departments of the University Hospitals of
      Geneva. These professionals included residents, fellows, certified nursing
      assistants, nurses, and nurse supervisors. All interviews were transcribed
      verbatim, and conventional content analysis was used to derive conflict
      characteristics. RESULTS: Six conflict sources were identified. Among these
      sources, disagreements on patient care tended to be the primary trigger of
      conflict, whereas sources related to communication contributed to conflict
      escalation without directly triggering conflict. A framework of workplace
      conflict that integrates its multidimensional and cyclical nature was
      subsequently developed. This framework suggests that conflict consequences and
      responses are interrelated, and might generate further tensions that could affect
      health care professionals, teams, and organizations, as well as patient care.
      Findings also indicated that supervisors' responses to contentious situations
      often failed to meet health care professionals' expectations. CONCLUSIONS:
      Understanding conflicts between health care professionals involves several
      interrelated dimensions, such as sources, consequences, and responses to
      conflict. There is a need to strengthen health care professionals' ability to
      identify and respond to conflict and to further develop conflict management
      programs for clinical supervisors.

PMID- 29065030
TI  - Using the Readiness for Clerkship and Residency Surveys to Evaluate the
      Effectiveness of Four MD Programs: A Cross-Institutional Generalizability Study.
AB  - PURPOSE: The importance of confidence for learning and performance makes
      learners' perceptions of readiness for the next level of training valuable
      indicators of curricular success. The "Readiness for Clerkship" (RfC) and
      "Readiness for Residency" (RfR) surveys have been shown to provide reliable
      ratings of the relative effectiveness of various aspects of training. This study
      examines the generalizability of those results. METHOD: Surveys were administered
      at four medical schools approximately four months after the start of clerkship
      and eight months after the start of residency during 2013-2015. Collected data
      were anonymized. A total of 647 medical students and 483 residents participated.
      RESULTS: Reliabilities of G = 0.8 could be obtained with only 6 to 12 medical
      students and 8 to 15 residents. Within MD programs, no meaningful differences in
      item ratings were observed across cohorts. Residents in each school consistently
      rated themselves higher than clerks on the majority of Medical Expert and
      Communicator competencies common to both surveys. Similar strengths and
      weaknesses were identified across programs, but differences were observed on five
      clerkship items and one residency item. CONCLUSIONS: Across four MD programs, the
      RfC and RfR surveys provided reliable ratings of the relative effectiveness of
      aspects of training with small numbers of respondents. The capacity of these
      surveys to efficiently identify perceived strengths and weaknesses held by
      cohorts of learners may, thereby, facilitate program improvement.

PMID- 29065031
TI  - EQual, a Novel Rubric to Evaluate Entrustable Professional Activities for Quality
      and Structure.
AB  - PURPOSE: Entrustable professional activities (EPAs) have become a cornerstone of
      assessment in competency-based medical education (CBME). Increasingly, EPAs are
      being adopted that do not conform to EPA standards. This study aimed to develop
      and validate a scoring rubric to evaluate EPAs for alignment with their purpose,
      and to identify substandard EPAs. METHOD: The EQual rubric was developed and
      revised by a team of education scholars with expertise in EPAs. It was then
      applied by four residency program directors/CBME leads (PDs) and four
      nonclinician support staff to 31 stage-specific EPAs developed for internal
      medicine in the Royal College of Physicians and Surgeons of Canada's Competency
      by Design framework. Results were analyzed using a generalizability study to
      evaluate overall reliability, with the EPAs as the object of measurement. Item
      level analysis was performed to determine reliability and discrimination value
      for each item. Scores from the PDs were also compared with decisions about
      revisions made independently by the education scholars group. RESULTS: The EQual
      rubric demonstrated high reliability in the G-study with a phi-coefficient of
      0.84 when applied by the PDs, and moderate reliability when applied by the
      support staff at 0.67. Item-level analysis identified three items that performed
      poorly with low item discrimination and low interrater reliability indices.
      Scores from support staff only moderately correlated with PDs. Using the
      preestablished cut score, PDs identified 9 of 10 EPAs deemed to require major
      revision. CONCLUSIONS: EQual rubric scores reliably measured alignment of EPAs
      with literature-described standards. Further, its application accurately
      identified EPAs requiring major revisions.

PMID- 29065033
TI  - Increased Incidence of Vascular Injury in Obese Patients With Knee Dislocations.
AB  - OBJECTIVES: With rising rates of obesity in the United States, the burden of knee
      dislocations in this population remains unknown. This national epidemiologic
      study was designed to analyze the association of obesity with closed knee
      dislocation and vascular complications. DESIGN: Retrospective cohort study.
      SETTING: The deidentified Nationwide Inpatient Sample database was used to access
      the US inpatient data from 2000 to 2012. PATIENTS/PARTICIPANTS: Patients with
      noncongenital closed knee dislocations were included. Examined variables included
      patient age, sex, vascular injury, and obesity status. MAIN OUTCOME MEASURES:
      Outcome measures included hospital length of stay, amputation, and inpatient
      hospitalization charge. RESULTS: From 2000 to 2012, a total of 19,087 knee
      dislocations were identified, including 2265 in overweight/obese patients
      (11.9%). The annual incidence of knee dislocations reported in patients diagnosed
      as either obese or morbidly obese increased over the 13-year period (P < 0.0001).
      The overall average rate of vascular injury requiring intervention was 5.63%,
      whereas 7.2% of obese patients and 11.3% of morbidly obese patients with knee
      dislocations (P < 0.0001) sustained a vascular injury requiring intervention. The
      average length of stay and amputation rate for obese and morbidly obese patients
      who sustained a knee dislocation was not statistically different from nonobese
      patients when vascular injury was controlled. When patients with a vascular
      injury were excluded, obese and morbidly obese patients who sustained a knee
      dislocation had higher average cost of hospital stay than nonobese patients (P =
      0.0262). CONCLUSIONS: This study demonstrates significant increases in costs of
      stay with obese patients sustaining knee dislocations when compared with normal
      weight knee dislocation patients. Vascular injuries were found to be far more
      common in obese and morbidly obese patient groups than nonobese patients.
      Providers should be on high alert when managing knee dislocations in obese
      patients because a significant number require prompt vascular intervention. LEVEL
      OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29065034
TI  - Is S3 a Viable Osseous Fixation Pathway?
AB  - OBJECTIVES: To report the incidence of patients with a third sacral segment (S3)
      osseous fixation pathway (OFP) that could accommodate a transiliac-transsacral
      screw. DESIGN: Retrospective case series. SETTING: Regional Level 1 Trauma
      Center. PATIENTS/PARTICIPANTS: A total of 250 patients without pelvic trauma from
      January 2017 to February 2017 were included. INTERVENTION: The axial and sagittal
      reconstruction images of each patient's computed abdomen and pelvis tomography
      (CT) scans were reviewed. MAIN OUTCOME MEASUREMENTS: Each CT was evaluated for
      the presence of sacral dysmorphism and whether an S3 OFP that could accommodate
      an intraosseous transiliac-transsacral screw exists. RESULTS: There were 130 of
      the 250 patients (52%) with sacral dysmorphism. Overall, 38 of the 250 patients
      (15.2%) had an S3 OFP that could accommodate a 7.0-mm transiliac-transsacral
      style screw. When narrowed to patients who had an S3 OFP, 38 of 153 patients
      (24.8%) could accommodate a 7.0-mm transiliac-transsacral screw. Specific to the
      38 patients with an adequate S3 OFP, 34 of 38 patients (89.5%) were noted to have
      sacral dysmorphism. CONCLUSIONS: Our study demonstrates that 15.2% of patients
      have an S3 OFP large enough to accommodate an intraosseous implant. Patients who
      have sacral dysmorphism are more likely to have an adequate S3 OFP. Additional
      studies are needed to quantify the S3 OFP, understand the bone quality of the S3
      segment and accompanying biomechanical implications, and investigate the
      anatomical concerns associated with S3 screw placement. LEVEL OF EVIDENCE:
      Prognostic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29065035
TI  - The Effect of Soft Tissue Injuries on Clinical Outcomes After Tibial Plateau
      Fracture Fixation.
AB  - OBJECTIVE: To determine if ligamentous and meniscal injuries as determined by
      initial magnetic resonance imaging altered clinical outcomes after the fixation
      of tibial plateau fractures. DESIGN: Comparative cohort study. SETTING: Academic
      level I trauma center. PATIENTS/PARTICIPANTS: Eighty-two patients from a
      prospective database of operatively treated tibial plateau fractures met the
      inclusion criteria, which consisted of injury radiographs, preoperative knee
      magnetic resonance imaging (MRI), and a minimum of 12 months of clinical
      outcomes. INTERVENTION: In addition to radiographs and computed tomography scans
      for fracture assessment, an MRI was performed to detect tears in the medial and
      lateral menisci and complete ruptures of the cruciate ligaments (anterior
      cruciate ligament and posterior cruciate ligament) and collateral ligaments
      [lateral collateral ligament and medial collateral ligament (MCL)]. Surgical
      fixation of tibial plateau fractures was performed by a single surgeon based on
      injury patterns. MAIN OUTCOME MEASUREMENTS: Clinical outcomes included the Knee
      Outcome Survey Activities of Daily Living Scale, the Lower Extremity Functional
      Scale, the Short-Form 36, and knee range of motion. Secondary soft tissue
      surgeries and conversion to arthroplasty were also noted. RESULTS: On injury MRI,
      60 patients (73%) had injuries to at least one soft tissue structure. At final
      follow-up, 2 patients (2%) had a secondary soft tissue surgery and 1 patient (1%)
      underwent total knee arthroplasty. Patient-reported outcomes and range of motion
      assessments were not significantly different in patients with and without medial
      meniscal tears, lateral meniscal tears, and complete MCL ruptures. CONCLUSIONS:
      In this cohort of patients with operative tibial plateau fractures, sutured
      lateral meniscal tears, untreated medial meniscus tears, and complete MCL
      ruptures did not significantly affect clinical outcomes. In addition, these data
      suggest that obtaining a preoperative MRI in patients with tibial plateau
      fractures to diagnose soft tissue injuries may not alter the surgical treatment
      or alter patient prognosis for midterm outcomes. LEVEL OF EVIDENCE: Prognostic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 29065036
TI  - Is It Safe to Prep the External Fixator In Situ During Second-Stage Pilon
      Surgical Treatment?
AB  - OBJECTIVE: To evaluate the infection rate of our protocol of prepping the
      external fixator in situ during definitive second-stage pilon fracture open
      reduction internal fixation. DESIGN: Retrospective clinical investigation.
      SETTING: Academic Level 1 Trauma Center. PATIENTS/PARTICIPANTS: Out of 229
      patients with distal tibia fractures presenting to our institution from 1999 to
      2014, 100 were treated in a 2-stage fashion utilizing this protocol.
      INTERVENTION: Prepping the external fixator into the surgical field during the
      second-stage/definitive open reduction internal fixation procedure. MAIN OUTCOME
      MEASUREMENT: The rates of deep and superficial infections after definitive
      fixation. RESULTS: The deep infection rate was 13%, and the superficial infection
      rate was 11%. CONCLUSIONS: Infection rates using this protocol are comparable to
      previously reported infection rates for two-stage surgical treatment of pilon
      fractures. This protocol provides the treating surgeon information about an
      alternative method to streamline definitive fixation. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29065037
TI  - Early Surgery Confers 1-Year Mortality Benefit in Hip-Fracture Patients.
AB  - BACKGROUND: To evaluate the relationship between surgical timing and 1-year
      mortality in patients requiring hip fracture repair. METHODS: We analyzed all 720
      patients (>65 years) who had hip fracture surgery between March 2005 and February
      2015, identifying patients by ICD-9 diagnosis and procedure codes using
      electronic data query. Mortality data were obtained from the institutional
      database, state and Social Security Death Indices. The relationship between
      surgical timing (defined as the interval from admission to the start of surgery)
      and 1-year mortality was assessed using a multivariable logistic regression,
      adjusting for baseline clinical status and surgical factors. RESULTS: Among the
      720 patients, 159 patients (22%) died within 1 year. The median time from
      admission to surgery was 30 hours. A linear relationship between the surgical
      timing and 1-year mortality was demonstrated. Delaying surgery was significantly
      associated with increased 1-year mortality, odds ratio 1.05 (95% CI: 1.02-1.08)
      per 10-hour delay (P = 0.001). CONCLUSIONS: A linear relationship was observed
      between surgical timing and 1-year mortality. Each 10-hour delay from admission
      to surgery was associated with an estimated 5% higher odds of 1-year mortality.
      Therefore, we suggest that hip fractures should be treated urgently similar to
      other time-sensitive pathology such as stroke and myocardial ischemia. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29065038
TI  - Provisional Plating of Subtrochanteric Femur Fractures Before Intramedullary
      Nailing in the Lateral Decubitus Position.
AB  - Subtrochanteric femur fractures remain a challenge for surgeons to obtain and
      maintain adequate reduction and stable fixation. For this reason, multiple
      techniques have been described, but we are unaware of a detailed contemporary
      description of the combination of provisional plating before intramedullary
      fixation in the lateral decubitus position. We present our technique as it was
      used from 2011 to 2015 to treat 22 fractures and how it compared clinically to
      the other 48 subtrochanteric femur fractures treated during that period. The
      clinical and radiographic outcomes for all fractures were evaluated. The
      operative time was shorter when no open reduction was used but open cases showed
      no significant difference when using a provisional plate. Those patients treated
      with provisional plating were shown to have higher blood loss values and longer
      operative times, but when looking at the outcomes, the rate of malunion, which
      was defined as >5 degrees of angulation on postoperative radiographs, was
      significantly lower at 0% in the provision plating in the lateral decubitus
      position subset compared with the remaining subtrochanteric fractures, 27.7% (P =
      0.013). As the quality of reduction and stability of fixation are the most
      significant factors in determining outcomes of subtrochanteric femur fractures,
      this study shows that this technique is a valuable tool in an orthopaedist's
      armamentarium and present it as such.

PMID- 29065039
TI  - Opioid Prescribing Practices by Orthopaedic Trauma Surgeons After Isolated Femur
      Fractures.
AB  - OBJECTIVE: The purpose of this retrospective study was to identify opioid
      prescribing practices, determine the number of morphine milliequivalents (MMEs)
      prescribed by orthopaedic/nonorthopaedic members to narcotic naive and previously
      exposed patients, and provide narcotic prescribing recommendations. METHODS:
      Patients older than 18 years with an isolated femur fracture sustained between
      2013 and 2015 were identified using the CPT code 27506. Prescribing information
      was obtained from the State Controlled Substance Monitoring Database. Descriptive
      analysis of MMEs was then performed. Outliers and patients without prescriptions
      from orthopaedic providers were excluded to eliminate skewing of data. Mean and
      standard deviations were then calculated for patients without a history of
      opiates prescribed within 1 year of injury and for patients with a history of
      opiates prescribed within 1 year before the injury. RESULTS: Forty-five percent
      (40/88) of patients were opiate exposed at the time of injury. Previously exposed
      patients received 1491 MMEs (SD, 1044; median, 1350; range, 210-5140) and
      nonexposed patients received 1363 MMEs (SD, 977.2; median, 1260; range, 105-4935)
      from orthopaedic providers (P = 0.1473). Nonorthopedists prescribed 530 MMEs (SD,
      780.7; median, 140; range, 0-3515) to previously exposed patients and 175 MMEs
      (SD, 393; median, 140; range, 0-1890) to patients without exposure (P < 0.0001).
      CONCLUSION: Patients with prior exposure are more likely to be prescribed more
      opiates after femoral shaft fracture treatment. We recommend a protocol of
      prescribing half the mean of MMEs currently prescribed by orthopedists equating
      to 47 (711 MMEs) pills of oxycodone 10 mg in up to 3 prescriptions.

PMID- 29065040
TI  - Cadaveric Biomechanical Analysis of 3 Lateral Ulnar Collateral Ligament
      Reconstructions.
AB  - OBJECTIVE: To biomechanically assess the angular stability provided by 3
      techniques for reconstruction of the lateral ulnar collateral ligament. METHODS:
      Eight cadaveric elbows were tested with the lateral collateral ligament complex
      intact, disrupted from the origin at the lateral epicondyle, and reconstructed
      with 3 different techniques using ulnar bone tunnels: a suture "lasso" or
      palmaris longus tendon "lasso" both docked with a metal button at the origin, and
      a doubled-over palmaris longus tendon docked with metal buttons at both the
      origin and ulnar insertion. Elbows were tested with a physiologic elbow
      simulator, and varus angular position was quantified with an optical tracking
      system. Statistical analysis was performed using a repeated measures analysis of
      variance test to determine whether significance existed, and a Tukey post hoc
      analysis to compare statistical difference between native, disrupted, and repair
      states. RESULTS: There was a statistically significant difference between all
      repairs and the disrupted state (P < 0.05). The varus angulation after the
      repairs showed that the suture reconstruction was closest to the native case. The
      tendon reconstructions were similar to each other but less similar to the native
      elbow. Quantitatively, the suture reconstruction was within an average of 0.86
      degrees of the native elbow throughout range of motion. CONCLUSIONS: A suture
      reconstruction was most similar to a native elbow, but both tendon
      reconstructions significantly improved angular stability under varus
      gravitational loads.

PMID- 29065041
TI  - Publication of Podium Presentations at the Orthopaedic Trauma Association Annual
      Meetings: 2008-2012.
AB  - OBJECTIVE: To determine journal publication rates of podium presentations from
      the OTA Annual Meetings between 2008 and 2012. METHODS: Podium presentations from
      the 2008 to 2012 OTA annual meeting were compiled from the Annual Meeting
      archives. During December 2016, and Google Scholar were performed using
      individual keywords in the abstract title and content. The results were reviewed
      for matches to the meeting abstracts with regard to the title, authors, and
      abstract content. Yearly publication rates were calculated, along with time to
      publication and common journals for publication. RESULTS: The publication rate
      for the 357 podium abstracts presented at the OTA between 2008 and 2012 was
      72.8%. Eighty-one percent of abstracts were from the US institutions. The mean
      time to publication from podium presentation was 23.4 months, and the most common
      journals of publication were Journal of Orthopaedic Trauma (45.4%) and The
      Journal of Bone & Joint Surgery (15.3%). CONCLUSIONS: The publication rate of the
      podium presentations at the OTA Annual Meeting from 2008 to 2012 has increased
      since previous years. Compared with other orthopaedic subspecialty and
      nonorthopaedic specialty meetings, the OTA publication rate is among the highest
      in the medical field. OTA annual meetings are an opportunity for early access to
      high-quality research in the area of orthopaedic trauma.

PMID- 29065042
TI  - A New Operative One-Wing Technique to Correct Fronto-Orbital Region in Unilateral
      Nonsyndromic Plagiocephaly.
AB  - Anterior plagiocephaly is a premature closing of unilateral coronal suture. This
      premature suture fusion causes a series of cranial asymmetry and alteration of
      the fronto-orbital region.The authors described a new surgical technique to
      correct the facial asymmetry that reduces the operative time and the possible
      complications.In a period between 2013and 2016, 12 children affected by
      nonsyndromic anterior plagiocephaly were treated with this new
      procedure.Clinical, cranial development, and absence of postoperative
      complication demonstrated that one-wing surgical bone correction is a useful and
      innovative technique.

PMID- 29065043
TI  - Defining and Correcting Asymmetry in Isolated Unilateral Frontosphenoidal
      Synostosis: Differences in Orbital Shape, Facial Scoliosis, and Skullbase Twist
      Compared to Unilateral Coronal Synostosis.
AB  - INTRODUCTION: Isolated frontosphenoidal synostosis (FS) is a rare cause of fronto
      orbital plagiocephaly that can be challenging to distinguish from isolated
      unicoronal synostosis (UC). The purpose of this paper is to analyze differences
      in fronto-orbital dysmorphology between the 2 conditions, to describe approaches
      for surgical correction, and to report surgical outcomes between FS and UC
      patients in a casecontrol fashion. METHODS: Patients treated for craniosynostosis
      over a 12-year period at our institution were retrospectively evaluated under
      institutional review board approval. Frontosphenoidal synostosis patients who
      underwent bilateral fronto-orbital correction of anterior plagiocephaly with
      minimum 2-year follow-up, adequate pre-, and minimum 2-year postoperative
      computed tomography scans were included in the case-control portion of the study.
      These patients were randomly age-matched to UC patients meeting the same
      inclusion criteria. Preoperative and postoperative orbital shape and volumetric
      analysis was performed using Mimics software. RESULTS: Twelve FS patients were
      treated during the study period. Seven of these patients met casecontrol
      inclusion criteria with average follow-up of 47.5 months. The characteristic FS
      orbit was a relatively wide, short, and shallow trapezoid, while the
      characteristic UC orbit was a relatively narrow, tall, and deep parallelogram.
      Frontosphenoidal synostosis orbits were significantly wider, shorter, shallower,
      and smaller than UC orbits. Surgical correction tailored to the differential
      dysmorphologies resulted in statistical equalization of these differences between
      affected and contralateral control orbits at follow-up, with the exception of UC
      orbital width, which remained significantly narrower than unaffected
      contralateral control. One patient in each group required cranioplasty for skull
      defects at follow-up, while no patient underwent surgical readvancement.
      CONCLUSIONS: Frontosphenoidal synostosis and UC orbital shape differ
      significantly, and can be normalized using fronto-orbital advancement tailored to
      the distinct orbital dysmorphologies of these 2 groups.

PMID- 29065045
TI  - Transorbital Penetrating Intracranial Injury by a Battery.
AB  - The authors report a patient of transorbital penetrating intracranial injury by a
      battery. A 59-year-old man presented with a foreign body in the left orbital
      region after an explosion during waste combustion. Physical examination revealed
      his left eyelid had been punctured and the eyeball ruptured by what appeared to
      be a battery, which was lodged in the left orbit. The patient was neurologically
      intact. Facial computed tomography showed a ca. 6.2 * 1.7 cm sized metallic
      foreign body, probably an electric battery, penetrating through the left orbit
      and orbital roof and terminating in the left anterior cranial fossa. Clinical
      presentation, treatment course, and follow-up are discussed.

PMID- 29065044
TI  - Osteogenesis of Crouzon-Mutated Cells in an Experimental Model.
AB  - Crouzon syndrome is an autosomal-dominant congenital disease due to a mutation in
      the fibroblast growth factor receptor 2 protein. The purpose of this study is to
      evaluate wound-healing potential of Crouzon osteoblasts and adipose-derived stem
      cells (ADSCs) in a murine model. Parietal skull defects were created in Crouzon
      and mature wild-type (WT) CD-1 mice. One group of WT and Crouzon mice were left
      untreated. Another group was transplanted with both WT and Crouzon adipose
      derived stem cells. Additional groups compared the use of a fibrin glue scaffold
      and periosteum removal. Skulls were harvested from each group and evaluated
      histologically at 8-week and/or 16-week periods. Mean areas of defect were
      quantified and compared via ANOVA F-test. The average area of defect after 8 and
      16 weeks in untreated Crouzon mice was 15.37 +/- 1.08 cm and 16.69 +/- 1.51 cm,
      respectively. The average area of the defect in untreated WT mice after 8 and 16
      weeks averaged 14.17 +/- 1.88 cm and 14.96 +/- 2.26 cm, respectively. WT mice
      with autologous ADSCs yielded an average area of 15.35 +/- 1.34 cm after 16 weeks
      while Crouzon mice with WT ADSCs healed to an average size of 12.98 +/- 1.89 cm.
      Crouzon ADSCs transplanted into WT mice yielded an average area of 15.47 +/- 1.29
      cm while autologous Crouzon ADSCs yielded an area of 14.22 +/- 3.32 cm. ANOVA F
      test yielded P = .415. The fibroblast growth factor receptor 2 mutation in
      Crouzon syndrome does not promote reossification of critical-sized defects in
      mature WT and Crouzon mice. Furthermore, Crouzon ADSCs do not possess osteogenic
      advantage over WT ADSCs.

PMID- 29065046
TI  - Cell Polarity and PAR Complex Likely to Be Involved in Dexamethasone-Induced
      Cleft Palate.
AB  - Accumulating studies demonstrated that PAR complex contributed to the
      establishment and maintenance of cell polarity which was fundamental to many
      aspects of cell and developmental biology. The purpose of this study was to
      investigate whether dexamethasone (DEX) could downregulate the PAR complex and
      disrupt cell polarity in palatal epithelium during palatal fusion in mice. The
      C57BL/6J mice were selected for the experiment. Pregnant mice in control group
      and DEX-treated group were injected intraperitoneally with 0.9% sodium chloride
      0.1 mL, which contained DEX 6 mg/kg respectively, every day from E10 to E12. The
      palatal epithelia morphology was observed with hematoxylin and eosin and scanning
      electron microscopy. Immunofluorescence staining, western blot, and real-time
      polymerase chain reaction were performed to detect the expression of
      PAR3/PAR6/aPKC. After being treated with DEX, the palatal shelves showed delayed
      development and became shorter and smaller. During the process of palatogenesis,
      PAR3 and PAR6 expressed in the palatal epithelium, and aPKC expressed in both the
      epithelium and the mesenchyme. Dexamethasone could downregulate the expression
      levels of PAR3/PAR6/aPKC in both protein and gene level. In conclusions, DEX
      affected the PAR complex of mouse embryonic palate, and could perturb the PAR
      complex and the cell polarity of medial edge epithelium cells, and caused the
      failure of palatal fusion.

PMID- 29065047
TI  - Corticotomy With a Palatal Bone-Borne Retractor for Correcting Severe Bimaxillary
      Protrusion.
AB  - BACKGROUND: This article presents an alternate surgical treatment method to
      correct a severe anterior protrusion in the adult patient with an extremely thin
      alveolus. METHODS: In the maxilla, a wide linear corticotomy was performed under
      local anesthesia. Cortical alveolar bone of the upper first bicuspids area was
      widely removed. Orthopedic force for bony block movement was applied by a palatal
      bone-borne type retractor supported by skeletal anchorage. Residual extraction
      space closure was performed by biocreative orthodontics strategy (BOS). In the
      mandible, an anterior segmental osteotomy (ASO) and extraction of 1st premolars
      were performed under local anesthesia. RESULTS: In the maxilla, bony block
      movement followed by the wide linear corticotomy with a palatal bone-borne type
      retractor was implemented without complications. Remaining extraction space after
      the bony block movement was closed effectively by BOS. In the mandible, anterior
      segmental retraction was achieved effectively by ASO. CONCLUSIONS: Wide linear
      corticotomy with a palatal bone-borne type retractor and ASO under local
      anesthesia can be an effective alternative to orthognathic surgery in adults with
      protrusion and an extremely thin alveolus. The biocreative strategy also provides
      a simple and effective method to retract the 6 anterior teeth.

PMID- 29065048
TI  - Primary Central Nervous System Lymphoma of Optic Chiasma: Endoscopic Endonasal
      Treatment.
AB  - BACKGROUND: Isolated primary central nervous system lymphoma arising from
      anterior visual pathway is very rare. PATIENT PRESENTATION: A 76-year-old
      immunocompetent previously healthy man presented bilateral decreased visual
      acuity in 1 month. Pituitary magnetic resonans imaging (MRI) showed a lobulated
      mass with homogeneous enhancement after gadolinium administration that arising
      from optic chiasm suggested that inflammatory disease or an optic glioma. The
      patient underwent an extended endoscopic endonasal transsphenoidal surgery.
      Postoperative course and outcomes were wonderful. Histopathological diagnosis was
      diffuse large B-cell lymphoma. The patient underwent investigations for systemic
      lymphomatous involvement, did not detect any evidence of systemic disease.
      CONCLUSION: In this case, we claimed that differential diagnoses of anterior
      visual pathway lesions are difficult because of similarity of lesions on clinical
      and radiological examinations. Biopsy is essential for these lesions. As a biopsy
      technique, endoscopic endonasal transsphenoidal approach is safer and more
      effective than open procedures.

PMID- 29065049
TI  - Bioinformatics Associated With Conjoined Twin Separation.
AB  - The separation of conjoined twins is a rare event in the medical field and
      presents many unique challenges to overcome. With the complexities of today's
      interconnected healthcare technology and electronic medical record, there are
      many intricate details that need significant attention to guarantee proper care
      and accurate record keeping for conjoined twins. Items that require attention are
      how to digitally represent the twins-as 1 patient or 2, how to incorporate the
      physiological monitors into the medical record, and how to ensure the proper
      amount of infrastructure, equipment, and space. With careful planning and
      consideration, technology can be used as an aid in separating conjoined twins at
      any institution.

PMID- 29065050
TI  - Method for Securing Methlymethacrylate Bone Cement Using Histoacryl Glue During
      Cranioplasty for Contour Deformities.
AB  - Methylmethacrylate bone cement (MM-BC) is one of the reconstructive methods:
      during cranioplasty to correct cranial defects following trauma or cranial
      surgery. Perfect intraoperative immobilization of the MM-BC is crucial to ensure
      correct subsequent shaping to best improve contour defects. Current
      immobilization techniques reported are time-consuming and involve complex
      metalwork. The authors hereby present a technique that may simplify the
      immobilization process by using histoacryl glue to secure the MM-BC. This
      provides a quick, inexpensive, and readily available option providing fixation
      strong enough to withstand final shaping of the MM-BC.

PMID- 29065052
TI  - Energy Drink Doses Of Caffeine And Taurine Have A Null Or Negative Effect On
      Sprint Performance.
AB  - This study investigated the effects of caffeine and taurine co-ingestion on
      repeat-sprint cycling performance and associated physiological and perceptual
      responses. In a double blind, cross-over, repeated measures study, 11 male
      participants (age 21 +/- 2 years; stature 178 +/- 7 cm; body mass 80 +/- 13 kg)
      completed 10 x 6-s sprints on a cycle ergometer, each separated by 24-s, an hour
      after ingesting: caffeine (80 mg) and taurine (1 g), equivalent to the amount
      observed in popular commercial energy drinks, or placebo (maltodextrin ~1 g) in a
      gelatine capsule. Performance was measured on a cycle ergometer, whilst blood
      lactate concentration (B[la]), rating of perceived exertion (RPE) and heart rate
      (HR) were measured at baseline (pre-exercise) and after sprints 5 and 10.
      Magnitude-based inferences revealed likely, trivial differences in peak power and
      unclear, trivial inter-sprint fatigue index after ingestion of the caffeine and
      taurine supplement. Intra-sprint fatigue was greater in the caffeine and taurine
      condition at sprint 10 (likely, small) and possibly smaller in sprints 6-9. The
      caffeine and taurine supplement had a likely large effect on HR at baseline (ES =
      0.94) and increases in B[la] after sprint 5 (likely small) and 10 (possibly
      small). There was no effect of the supplement on RPE (unclear, trivial).
      Administration of caffeine and taurine at doses equivalent to commercial energy
      drinks did not improve repeat-sprint cycling performance and appeared to induce
      greater fatigue within selected sprints, particularly at the end of the trial.
      This undesirable performance effect occurs in parallel with increased HR and
      glycolytic metabolic bi-products.

PMID- 29065051
TI  - Relationship of a Metopic Ridge and Anterior Cranial Volume Measured by a
      Noninvasive Laser Shape Digitizer.
AB  - Cranial dysmorphology observed in patients with metopic craniosynostosis varies
      along a spectrum of severity including varying degrees of metopic ridging,
      bitemporal narrowing, and trigonocephaly. Management has been based upon the
      subjective clinical impression of presence and severity of trigonocephaly.
      Severity of cranial dysmorphology does not predict the occurrence or severity of
      associated abnormal neurodevelopment, as children with mild-to-moderate
      trigonocephaly may also experience developmental delays. The authors sought to
      determine the relationship between mild-to-moderate trigonocephaly and anterior
      cranial volume using a noninvasive laser shape digitizer (STARscanner) in
      patients with abnormal head shape.An IRB-approved retrospective review of a
      prospectively maintained database and medical records was performed. Two hundred
      three patients less than 1 year of age with abnormal head shape were categorized
      as having a metopic ridge with mild-to-moderate trigonocephaly, metopic ridge
      without trigonocephaly, or no ridge. Measurements of cranial volume,
      circumference, and symmetry were calculated by the STARscanner, which quantifies
      three-dimensional shape of the cranial surface. Measures were analyzed using a
      series of analyses of variance and post-hoc Tukey honest significant
      difference.The authors results showed ACV was significantly reduced in patients
      with mild-to-moderate trigonocephaly compared with those without metopic ridge (P
      = 0.009), and trended toward significance compared with those with a ridge but
      without trigonocephaly (P = 0.072). The ratio of anterior-to-posterior cranial
      volume was significantly reduced in those with mild-to-moderate trigonocephaly
      compared with those without metopic ridge (P = 0.036).In conclusion, patients
      with milder anterior cranial deformities demonstrated an association between a
      metopic ridge with mild-to-moderate trigonocephaly and reduced anterior cranial
      volume.

PMID- 29065053
TI  - Physical Characteristics Of Youth Elite Golfers And Their Relationship With
      Driver Clubhead Speed.
AB  - Increased clubhead speed (CHS) has a strong relationship with golf performance
      and is related to athletic qualities in adult golfers. Research investigating the
      youth golfer is limited. The purpose of this study was to explore the
      relationships between strength and power on CHS in youth golfers. A correlational
      design was used to assess relationships between CHS and anthropometric, strength
      and power measurements. 36 male and 33 female golfers aged 13-17 took part in
      this study. Male golfers showed significant relationships between CHS and
      handicap (HCP) (r=-0.50), seated medicine ball throw to the left (SMBTL)
      (r=0.67), and right (SMBTR) (r=0.61), rotational medicine ball throw to the left
      (RMBTL) (r=0.71), and right RMBTR (r=0.62). Female golfers showed significant
      relationships between CHS and HCP (r=-0.52), mass (r=0.72), countermovement jump
      (CMJ) power (r=0.60), RMBTL (r=0.57), RMBTR (r=0.56). Multiple stepwise linear
      regression analysis identified 77% of the variance in CHS could be explained
      through SMBTL and RMBTL in males. In females 84% of the variance in CHS could be
      explained through mass, RMBTR and height. This study demonstrated relationships
      between CHS and body mass and upper, lower and full body concentric dominant
      power exercises. This study could aid in the development of training
      interventions for youth golfers.

PMID- 29065054
TI  - The Importance of Body Composition in the National Hockey League Combine
      Physiologic Assessments.
AB  - The National Hockey League (NHL) combine was designed to assess draft-eligible
      players based on body composition, speed, power, and strength. The importance of
      body composition in the battery of combine physical tests was investigated and
      differences in results based on position were explored. Thirty-seven elite male
      Canadian university hockey players (age = 22.86 +/- 1.55 years, weight = 87.21 +/
      6.52 kg, height = 181.69 +/- 6.19 cm) participated in the study at the beginning
      of their hockey season. All participants underwent physical testing (as outlined
      in the 2016 NHL combine) and one total body dual energy x-ray absorptiometry
      (DXA) scan to measure body composition. Partial correlations (controlling for
      weight) were used to explore the relationship among body composition measures
      (body fat percentage, visceral fat, BMI, lower lean tissue mass, upper lean
      tissue mass, upper fat mass, lower fat mass) with NHL fitness tests (bench press,
      pull-ups, grip strength, long jump, pro-agility, vertical jump, V O2max, and the
      Wingate Anaerobic Test). In 4 of the 6 strength/power tests (Wingate Anaerobic
      Test, long jump, bench press, and both grip strengths) lower and upper lean
      tissue mass explained significant amounts of variance. Although forwards and
      defensemen significantly differed in right grip strength and pro-agility left
      scores, they did not differ in regards to any body composition variables. Body
      composition has a significant influence on several combine-specific tests, which
      may help sport scientists and strength and conditioning coaches better tailor
      training programs to optimize performance in elite hockey players.

PMID- 29065055
TI  - Police Officers Who Are Physically Active and Have Low Levels of Body Fat Show
      Better Reaction Time.
AB  - OBJECTIVE: To analyze the relationship between reaction time (RT), level of
      physical activity (PA), and anthropometric indicators in police officers in
      Special Operation Units. METHODS: Twenty-two police officers (34.5 +/- 9.1 years
      old) from Santa Catarina, Brazil, who were members of a Special Operation
      Coordination Unit. RT was measured by the Vienna Test System. Were obtained
      values of body mass index (BMI), body fat (BF), and waist-to-hip ratio. PA was
      investigated using the Physical Activity Evaluation Questionnaire. RESULTS:
      Younger police officers (less than 34 years) and BF less than 15% presented
      better performance in RT when compared with older, and BF more than 15%,
      respectively. RT was negatively related to PA (rho = -0.48, P < 0.05), and
      positively related to BF (rho = 0.76, P < 0.01) and to BMI (rho = 0.46, P <
      0.05). CONCLUSIONS: Participants from the group with greater BF and insufficient
      PA reacted significantly slower than others.

PMID- 29065057
TI  - Using the CDC Worksite Health ScoreCard to Assess Employer Health Promotion
      Efforts: A Case Study at Johns Hopkins Medicine.
AB  - OBJECTIVES: The aim of this study was to determine whether the Centers for
      Disease Control and Prevention Worksite Health ScoreCard (ScoreCard) is an
      effective vehicle for measuring workplace health promotion programs and causing
      change in a large employer with multiple entities defined by different physical
      environments and types of workers. METHODS: Johns Hopkins Medicine (JHM)
      representatives completed a baseline ScoreCard for each of their entities. In the
      subsequent year, improvement of the ScoreCard was tied to leadership performance
      evaluation. JHM year over year scores were analyzed, along with comparisons to
      national benchmarks. RESULTS: Eleven of the 12 JHM entities improved their
      overall score from year one to year two and the JHM enterprise surpassed national
      benchmarks in year two. CONCLUSION: Organizations can use the ScoreCard as an
      effective measurement tool and as a method to improve the number of evidenced
      based health promotion strategies provided to their employees.

PMID- 29065056
TI  - Self-Rated Health of the Temporary Employees in a Nordic Welfare State: Findings
      From the Finnish Public Sector Study.
AB  - OBJECTIVE: This 9-year follow-up study explores a possible association between
      temporary employment and declining health. METHODS: Years in temporary employment
      from 2004 to 2008 to 2009 were measured for a cohort of 26,886 public sector
      employees. Self-rated health was measured by surveys in 2004 (baseline),
      2008/2009 (short-term follow-up), and 2012/2013 (long-term follow-up). RESULTS:
      Compared with the permanently employed, the baseline health-adjusted odds of poor
      health were lower both in the short-term and long-term follow-up, but the
      differences became nonsignificant when adjusted for sociodemographic and work
      related factors. CONCLUSION: The results would suggest that temporary employment
      in public sector of a Nordic welfare state does not entail health risks. Future
      research is needed to elucidate if this is true also among those exposed to
      nonpermanent employment in the private labor market, in particular those with
      most atypical jobs and unstable job careers.

PMID- 29065058
TI  - Ensuring the Right to Rest: City Ordinances and Access to Rest Breaks for Workers
      in the Construction Industry.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of city Rest
      Break Ordinance (RBO) policies in expanding access to rest at work. METHODS: We
      use data from surveys of construction workers in Austin and Dallas, Texas, in
      2009, 2012, and 2015 (n = 557) to calculate the odds of receiving a rest break in
      pre- versus post-RBO Austin and in post-RBO Austin versus pre-RBO Dallas,
      controlling for demographic and employment characteristics. RESULTS: Construction
      workers were 35% more likely to report receiving a rest break in Austin post-RBO
      and 16% less likely in Dallas without a RBO as compared to Austin with a RBO.
      CONCLUSION: The increased likelihood of receiving rest breaks at work in a RBO
      city suggests that, in the absence of enforceable national standards, city-level
      RBOs can be an important first step to effective prevention of heat-related
      illnesses (HRIs) and heat-related fatalities at work.

PMID- 29065059
TI  - Characteristics of Decreased Pulmonary Function and Clinical Symptoms in Nickel
      Electroplating Workers.
AB  - OBJECTIVE: To investigate health problems, especially pulmonary function, among
      electroplating workers exposed to nickel. METHODS: We recruited 153 nickel
      exposed and 74 control workers from electroplating shops in printed circuit board
      production plants. Questionnaires were conducted to collect basic information.
      Symptoms and pulmonary function were ascertained. RESULTS: The average urine
      nickel level of the 79 high-exposure, 74 low-exposure, and 74 control workers
      were 7.38 +/- 5.96, 5.79 +/- 4.75, and 5.27 +/- 3.89 MUg/g Cr, respectively.
      Nickel-exposed workers had a significantly higher incidence of skin- and airway
      based symptoms. A significant relationship between impaired pulmonary function
      and high (more than5.2 MUg/g Cr) urine nickel level was observed. CONCLUSIONS:
      Nickel-exposed workers had significantly higher urine nickel levels with more
      skin-, airway-based symptoms, as well as impaired pulmonary function. A dose
      response relationship between decreased pulmonary function and nickel exposure
      status was observed.

PMID- 29065060
TI  - Emerging Occupational Health Needs at a Semiconductor Factory Following the 2016
      Kumamoto Earthquakes: Evaluation of Effectiveness and Necessary Improvements of
      List of Postdisaster Occupational Health Needs.
AB  - OBJECTIVES: We sought to share our experiences with occupational health efforts
      at a manufacturing site after a large earthquake event, and to evaluate the
      effectiveness of our "List of Occupational Health Needs Following Disasters"
      (Needs List). METHODS: We implemented occupational health efforts following the
      2016 Kumamoto earthquakes in Japan, with reference to the Needs List and a
      related manual, and analyzed the needs that arose. RESULTS: The instruments used
      enabled occupational health personnel to predict what needs would arise and
      facilitate their countermeasures. Among such needs that arose, 87.7% were in the
      Needs List, but seven undocumented needs were also observed. CONCLUSION: We
      confirmed that the Needs List could predict as many occupational health needs as
      we had expected at the disaster, though it is necessary to improve them by
      reflecting on our experiences.

PMID- 29065061
TI  - A National Study Links Nurses' Physical and Mental Health to Medical Errors and
      Perceived Worksite Wellness.
AB  - OBJECTIVE: The aim of this study was to describe (1) nurses' physical and mental
      health; (2) the relationship between health and medical errors; and (3) the
      association between nurses' perceptions of wellness support and their health.
      METHODS: A cross-sectional descriptive survey was conducted with 1790 nurses
      across the U.S. RESULTS: Over half of the nurses reported suboptimal physical and
      mental health. Approximately half of the nurses reported having medical errors in
      the past 5 years. Compared with nurses with better health, those with worse
      health were associated with 26% to 71% higher likelihood of having medical
      errors. There also was a significant relationship between greater perceived
      worksite wellness and better health. CONCLUSION: Wellness must be a high priority
      for health care systems to optimize health in clinicians to enhance high-quality
      care and decrease the odds of costly preventable medical errors.

PMID- 29065062
TI  - Impact of Obesity on Work Productivity in Different US Occupations: Analysis of
      the National Health and Wellness Survey 2014 to 2015.
AB  - OBJECTIVE: The aim of this study was to quantify the relationship between
      workers' body mass index and work productivity within various occupations.
      METHODS: Data from two administrations (2014 and 2015) of the United States (US)
      National Health and Wellness Survey, an Internet-based survey administered to an
      adult sample of the US population, were used for this study (n = 59,772).
      Occupation was based on the US Department of Labor's 2010 Standardized Occupation
      Codes. Outcomes included work productivity impairment and indirect costs of
      missed work time. RESULTS: Obesity had the greatest impact on work productivity
      in Construction, followed by Arts and Hospitality occupations. Outcomes varied
      across occupations; multivariable analyses found significant differences in work
      productivity impairment and indirect costs between normal weight and at least one
      obesity class. CONCLUSION: Obesity differentially impacted productivity and
      costs, depending upon occupation.

PMID- 29065063
TI  - Child seat belt guidelines: Examining the 4 feet 9 inches rule as the standard.
AB  - BACKGROUND: Current American Academy of Pediatrics recommendations regarding
      transition from child safety/booster seat to adult safety belt use indicate that
      children should be at least 4 feet 9 inches, 8 years old, or 80 pounds. Proper
      fit in the vehicle seat, assessed with a five-point fit test, should also be met.
      Although most children reach 4 feet 9 inches around age 8 years, each child and
      vehicle presents a unique combination; thus a child may not fit appropriately in
      all vehicle types using only the 4 feet 9 inches requirement. METHODS: We
      enrolled children, aged 7 years to 12 years, into our study. Height, weight, and
      demographic data were obtained. A Child Passenger Safety Technician then
      performed the five-point fit test in each of a uniform lineup of five vehicles.
      Data were collected on fit in the standard vehicle seat and also in a booster
      seat. We set 90% as the threshold proportion of children who meet all criteria
      for proper fit to validate current recommendations of a height of 4 feet 9
      inches. RESULTS: Data were collected on 388 children. The percentage of 90%
      proper fit was met in the compact car and small sport-utility vehicle (SUV).
      However, only 80 (77%) of 104 students (p < 0.0001) that were 4 feet 9 inches or
      higher fit properly in the large SUV, only 87 (83%) of 105 students (p = 0.02)
      fit properly in the pickup truck, and only 91 (89%) of 102 students (p = 0.74)
      fit properly in the minivan. CONCLUSION: Substantial proportions of children
      meeting current height guidelines for an adult seat belt do not meet safety
      requirements for fit, especially in larger, commonly used vehicles (large SUVs
      and trucks). This emphasizes the need for evaluation of fit by a trained
      personnel and/or development of standard back seat dimensions in all vehicles for
      maximum safety. LEVEL OF EVIDENCE: Epidemiologic level 1.

PMID- 29065064
TI  - A multiyear assessment of a hospital-school program to promote teen motor vehicle
      safety.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of death among teen
      drivers. The main goal of this program was to reduce texting while driving among
      high school teens through a unique peer-generated anti-texting campaign. METHODS:
      The program consisted of two phases. In phase 1, student leaders participated in
      a half-day, hospital-based experiential program that emphasized safe teen
      driving. In phase 2, these students conceptualized and implemented an anti
      texting while driving campaign during the school year. The program enrolled 32
      schools with 137 student participants in phase 1. This study uses a prospective
      quasi-experimental pre-post design. A presurvey and a follow-up online survey
      were used. Response rate was 81%. In phase 2, two rounds of observations of
      drivers were made near the participating schools at the beginning and end of the
      phase 2 campaign. The results were analyzed using proportion tests. RESULTS:
      There was a strong belief (6.49 on a seven-point scale) that texting while
      driving could result in a crash. About 58% had texted while driving in the
      previous 7 days in the pre-survey. This proportion decreased significantly to 44%
      in the follow-up (p < 0.05). Knowledge of Tennessee Graduated Driver Licensing
      laws and feeling of empowerment to take action with a teen driver who was texting
      improved significantly (p < 0.05). In phase 2, 12,309 drivers (adults and teens)
      were observed in the first round, and 13,153 were observed in the second round of
      observations. Significant reduction in the proportion of drivers texting while
      driving (from 13% to 9%; p < 0.0001) was observed. CONCLUSION: Results of driver
      observations support the effectiveness of this program in meeting the key
      objective of reducing texting while driving. The program also influenced
      teenagers' willingness to take positive steps when faced with a driver who was
      texting. Future efforts should aim to influence social and peer norms. LEVEL OF
      EVIDENCE: Therapeutic study, level IV.

PMID- 29065065
TI  - A cross-sectional study of emergency care utilization and associated costs of
      violent-related (assault) injuries in the United States.
AB  - BACKGROUND: Violent-related (assault) injuries are a leading cause of death and
      disability in the United States. Many violent injury victims seek treatment in
      the emergency department (ED). Our objectives were to (1) estimate rates of
      violent-related injuries evaluated in United States EDs, (2) estimate linear
      trends in ED visits for violent-related injuries from 2000 to 2010, and (3) to
      determine the associated health care and work-loss costs. METHODS: We examined
      adults 18 years and older from a nationally representative survey (the National
      Hospital Ambulatory Medical Care Survey) of ED visits, from 2000 to 2010. Violent
      injury was defined using International Classification of Diseases-9th Rev.
      Clinical Modification, diagnosis and mechanism of injury codes. We calculated
      rates of ED visits for violent injuries. Medical and work-loss costs accrued by
      these injuries were calculated for 2005, inflation-adjusted to 2011 dollars using
      the WISQARS Cost of Injury Reports. RESULTS: An annual average of 1.4 million
      adults were treated for violent injuries in EDs from 2000 to 2010, comprising
      1.6% (95% confidence interval, 1.5%-1.6%) of all US adult ED visits. Young adults
      (18-25 years), men, nonwhites, uninsured or publically insured patients, and
      those residing in high poverty urban areas were at increased risk for ED visits
      for violent injury. The 1-year, inflation-adjusted medical and work-loss cost of
      violent-inflicted injuries in adults in the United States was US $49.5 billion.
      CONCLUSION: Violent injuries account for over one million ED visits annually
      among adults, with no change in rates over the past decade. Young black men are
      at especially increased risk for ED visits for violent injuries. Overall, violent
      related injuries resulted in substantial financial and societal costs. LEVEL OF
      EVIDENCE: Epidemiological study, level III.

PMID- 29065067
TI  - The 2019 Magnet(r) Application Manual: Nursing Excellence Standards Evolving With
      Practice.
AB  - The American Nurses Credentialing Center's Magnet Recognition Program(r) released
      the 2019 Magnet(r) Application Manual () in October. The 2019 manual is the 12th
      application manual in the 27-year history of the program. The manual builds upon
      the foundation of seminal research conducted in the early 1980s that led to the
      creation of the program yet incorporates contemporary standards that address
      challenges faced globally by healthcare organizations today.

PMID- 29065066
TI  - Severe Burn-Induced Inflammation and Remodeling of Achilles Tendon in a Rat
      Model.
AB  - Severe burn causes systemic inflammation and hypercatabolism, resulting in damage
      to multiple organs distant to the burn site, including the musculoskeletal
      system. Bone mass and muscle loss have been reported. However, tendon that
      connects bone and muscle has not been studied in comparable detail. Here we aimed
      to characterize the molecular and functional changes in Achilles tendon triggered
      by severe burn. Forty male Sprague-Dawley rats received 40% total body surface
      area scald burn. Achilles tendons were collected up to 14 days postburn. Sham
      treated animals served as a control group. We analyzed tendons for changes in
      expression of IL-6, IL-1beta, TNF, MMP9, MMP13, TGFbeta1, Collagens I and III,
      and for morphological and biomechanical changes. Gene expression of IL-6 and IL
      1beta as well as MMP9 and MMP13 increased in rat tendon 3 days after burn. Col3a1
      increased at day 3 and col1a1 at day 7. At day 14, TGFbeta1 increased, whereas
      the protein ratio for collagens I/III decreased, indicating tendon remodeling.
      Histological analysis with H&E and Picrosirius red staining further revealed a
      decrease in organized collagen fibers 14 days after burn. Biomechanical analysis
      showed a decrease in stiffness and ultimate force of tendons in burn rats.We
      conclude that tendinopathy was observed in Achilles tendon 14 days after severe
      burn, via the induction of inflammation and remodeling. The present study
      provides a model of tendinopathy that may be used for the development of
      therapeutic approaches after burn.

PMID- 29065068
TI  - Supporting Clinical Nurses Through a Research Fellowship.
AB  - After reviewing the literature, nurses at the bedside seeking answers to clinical
      questions may find their inquiries remain unanswered. This article describes the
      yearlong Research Fellows Program in which candidates, funded for 12 hours per
      month of research release time, answered formal research questions in a
      curriculum designed to provide the skills to complete their study. Five have
      completed their studies; 1 has received a grant to continue. Two are in process
      of submitting manuscripts to journals.

PMID- 29065069
TI  - Consumer-Centric Care: Latest Buzzword or New Reality?
AB  - With the industry in flux as federal healthcare reform legislation debates
      continue, leaders are preparing for what the post-Affordable Care Act world might
      look like. Predictions include patients assuming more responsibility for
      healthcare costs and therefore behaving like consumers, including choosing
      providers based on perceived value. What actions should chief nurse executives
      take to ensure the nursing enterprise responds to rising consumerism in
      healthcare?

PMID- 29065070
TI  - Circle of Advisors: Creating a National Perspective for Graduate Curricula in
      Nursing Administration.
AB  - The CGEAN Board established a goal to support MSN administration programs to
      thrive and meet the need for well-prepared nurses to assume leadership roles.
      This column addresses how we embarked on this work through creation of a Circle
      of Advisors composed of national nursing leaders who came together to address
      specific curricular issues and more importantly to voice support for continuation
      of MSN administration programs.

PMID- 29065071
TI  - Combining Best Practices and Patient, Caregiver, and Healthcare Provider
      Perspectives for Late-Life Supportive Care: LifeCourse.
AB  - Healthcare systems seek effective ways to support and treat the growing number of
      individuals living with serious illness. The nature of these care episodes
      challenges delivery systems to attain proficiency in dealing with the
      multiplicity of chronic conditions in individuals and populations through
      understanding and attending to patients' medical and nonmedical aspects of
      health. This article describes LifeCourse, a healthcare approach that provides
      palliative care practices to patients with serious illness years prior to death.

PMID- 29065072
TI  - Preparing for Electronic Medical Record Implementation: Carolina Care
      Communication in an Electronic Environment.
AB  - This article describes 1 organization's successful approach to mitigating the
      potential negative effects of a new electronic medical record on patient
      experience. The Carolina Care model, developed at the University of North
      Carolina Hospitals to actualize caring theory in practice, helped to structure
      and greatly facilitate this work. Seven focus areas were integrated to create the
      "Communication in an Electronic Environment" program with a strong emphasis on
      nurse-patient communication.

PMID- 29065073
TI  - Exploring Acuity-Adaptable Care in a Rural Hospital.
AB  - OBJECTIVE: The objective of this study is to assess benefits of the acuity
      adaptable (AA) care model in rural hospitals. BACKGROUND: The AA model aims to
      provide care in the same space from admission to discharge regardless of acuity.
      Evidence is lacking to support claims that AA care will improve patient safety,
      increase nurse productivity, and improve patient/staff satisfaction in rural
      hospitals. METHODS: Patients admitted to a rural intensive care unit (ICU) were
      allocated to an AA group or an ICU group. Patients in the AA group remained in
      the ICU room through discharge. Patients in the ICU group transferred out of ICU
      when acuity permitted. Patient anxiety, depression, and perception of emotional
      care were measured. Staff responses were assessed qualitatively. RESULTS: Acuity
      adaptable patients reported significantly more anxiety and less perceived
      emotional care than ICU patients. Intensive care unit nurses resisted caring for
      less acute patients. CONCLUSION: Disadvantages may outweigh benefits of AA care
      delivery in the rural ICU.

PMID- 29065075
TI  - Pachydermodactyly.

PMID- 29065074
TI  - A Pilot Study to Examine the Relationship Between Napping and Fatigue in Nurses
      Practicing on the Night Shift.
AB  - OBJECTIVE: The aim of this study is to explore the relationship of night-shift
      napping on fatigue. BACKGROUND: Nurses' fatigue, especially at night, interferes
      with quality of life and job performance and impacts safety and health. METHODS:
      Night-shift nurses completed the Brief Fatigue Inventory and a demographic
      information sheet to determine differences in fatigue between nurses who napped
      during their night shift as compared with nurses who did not nap. RESULTS: No
      statistically significant differences in global fatigue were found; differences
      in rotating shift, age, and, gender were identified. Rotating shifts, a 2nd job,
      and caring for family predicted fatigue. CONCLUSIONS: Based on this pilot study,
      further investigations of fatigue among night-shift nurses are needed as well as
      evidence-based support to promote sleep.

PMID- 29065076
TI  - Effects of Two Training Modalities on Body Fat and Insulin Resistance in
      Postmenopausal Women.
AB  - Henriquez, S, Monsalves-Alvarez, M, Jimenez, T, Barrera, G, Hirsch, S, de la
      Maza, MP, Leiva, L, Rodriguez, JM, Silva, C, and Bunout, D. Effects of two
      training modalities on body fat and insulin resistance in postmenopausal women. J
      Strength Cond Res 31(11): 2955-2964, 2017-Our objective was to compare the
      effects of a low-load circuit resistance training protocol and usual aerobic
      training in postmenopausal women. Postmenopausal women with at least 1 feature of
      the metabolic syndrome were randomly allocated to a low-load circuit resistance
      training protocol or traditional aerobic training in a braked cycle ergometer.
      The intervention consisted in supervised sessions lasting 40 minutes, 3 times per
      week, during 6 months. At baseline and at the end of the intervention, fasting
      serum lipid levels, serum interleukin 6, C-reactive protein, 8 isoprostanes, and
      insulin resistance (assessed through QUICKI and HOMA-IR) were measured. Body fat
      was measured by double-beam X-ray absorptiometry and by computed tomography
      densitometric quantification at lumbar 3 vertebral level. Twenty-one women aged
      58 (54-59) years were allocated to aerobic training and 21 women aged 55 (52-61)
      years were allocated to the low-load circuit resistance training protocol.
      Eighteen and 16 women in each group completed the 6 months training period. Women
      in both groups experienced significant reductions in blood pressure, total body,
      subcutaneous, and intraabdominal body fat. Reductions in total cholesterol and
      triacylglycerol levels were also observed. No changes in insulin resistance
      indexes, 8 isoprostanes, C-reactive protein, or interleukin 6 were observed in
      either group. No significant differences between treatment groups were observed
      in any of the measured parameters. We conclude that low-load circuit resistance
      training and aerobic training resulted in the same reductions in body fat and
      serum lipid levels.

PMID- 29065078
TI  - Biomechanical Differences of Multidirectional Jump Landings Among Female
      Basketball and Soccer Players.
AB  - Taylor, JB, Ford, KR, Schmitz, RJ, Ross, SE, Ackerman, TA, and Shultz, SJ.
      Biomechanical differences of multidirectional jump landings among female
      basketball and soccer players. J Strength Cond Res 31(11): 3034-3045, 2017
      Anterior cruciate ligament (ACL) injury prevention programs are less successful
      in basketball than soccer and may be due to distinct movement strategies that
      these athletes develop from sport-specific training. The purpose of this study
      was to identify biomechanical differences between female basketball and soccer
      players during multidirectional jump landings. Lower extremity biomechanics of 89
      female athletes who played competitive basketball (n = 40) or soccer (n = 49) at
      the middle- or high-school level were analyzed with 3-dimensional motion analysis
      during a drop vertical jump, double- (SAG-DL) and single-leg forward jump (SAG
      SL), and double- (FRONT-DL) and single-leg (FRONT-SL) lateral jump. Basketball
      players landed with either less hip or knee, or both hip and knee excursion
      during all tasks (p <= 0.05) except for the SAGSL task, basketball players landed
      with greater peak hip flexion angles (p = 0.04). The FRONT-SL task elicited the
      most distinct sport-specific differences, including decreased hip adduction (p <
      0.001) angles, increased hip internal rotation (p = 0.003), and increased
      relative knee external rotation (p = 0.001) excursions in basketball players. In
      addition, the FRONT-SL task elicited greater forces in knee abduction (p = 0.003)
      and lesser forces in hip adduction (p = 0.001) and knee external rotation (p <
      0.001) in basketball players. Joint energetics were different during the FRONT-DL
      task, as basketball players exhibited less sagittal plane energy absorption at
      the hip (p < 0.001) and greater hip (p < 0.001) and knee (p = 0.001) joint
      stiffness. Sport-specific movement strategies were identified during all jump
      landing tasks, such that soccer players exhibited a more protective landing
      strategy than basketball players, justifying future efforts toward sport-specific
      ACL injury prevention programs.

PMID- 29065077
TI  - Optimizing Half Squat Postactivation Potential Load in Squat Jump Training for
      Eliciting Relative Maximal Power in Ski Jumpers.
AB  - Golas, A, Wilk, M, Stastny, P, Maszczyk, A, Pajerska, K, and Zajac, A. Optimizing
      half squat postactivation potential load in squat jump training for eliciting
      relative maximal power in ski jumpers. J Strength Cond Res 31(11): 3010-3017,
      2017-Training load manipulation in a single workout session can increase or
      decrease training effectiveness in terms of athletes' strength or power gains. In
      ski jumping, the complex training that elicits maximal power gains may take
      advantage of the postactivation potentiation (PAP) mechanism. The aim of this
      research was to evaluate the changes in rate of force development (RFD), rate of
      power development (RPD), and jump height during a complex training session
      consisted of the barbell half squat (Sq) as a conditioning exercise with loads
      ranged between 60 and 100% of 1 repetition maximum (1RM), followed by a body
      weight squat jump (SqJ) as a performance task. The study was conducted with 16
      elite athletes from the Polish National Ski Jumping Team, age 23 +/- 8 years,
      body mass 56 +/- 9 kg, and height 172 +/- 12 cm. Complex training session started
      with the Sq at 60% of 1RM as the conditioning exercise, followed by 3 minutes of
      rest and the SqJ. The conditioning barbell half Sq was performed with 70, 80, 90,
      and 100% of 1RM with 5 minutes of rest. The differences in RFD occurred between
      an SqJ following the application of 80% of 1RM and all other SqJs (p = 0.01), and
      in RPD between SqJ without conditioning, SqJ after 60% of 1RM and 80% of 1RM (p =
      0.02). On average, the most effective load in inducing PAP during ski jumpers'
      SqJ training is 80% of 1RM. The intensity of the conditioning exercise that
      elicits the greatest PAP effect should be individualized (60-100% 1RM), as it is
      dependent on the level of maximal strength.

PMID- 29065079
TI  - Leg Stiffness in Female Soccer Players: Intersession Reliability and the
      Fatiguing Effects of Soccer-Specific Exercise.
AB  - De Ste Croix, MBA, Hughes, JD, Lloyd, RS, Oliver, JL, and Read, PJ. Leg stiffness
      in female soccer players: intersession reliability and the fatiguing effects of
      soccer-specific exercise. J Strength Cond Res 31(11): 3052-3058, 2016-Low levels
      of leg stiffness and reduced leg stiffness when fatigue is present compromise
      physical performance and increase injury risk. The purpose of this study was to
      (a) determine the reliability of leg stiffness measures obtained from contact mat
      data and (b) explore age-related differences in leg stiffness after exposure to a
      soccer-specific fatigue protocol in young female soccer players. Thirty-seven
      uninjured female youth soccer players divided into 3 subgroups based on
      chronological age (under 13 [U13], under 15 [U15], and under 17 [U17] year-olds)
      volunteered to participate in the study. After baseline data collection, during
      which relative leg stiffness, contact time, and flight time were collected,
      participants completed an age-appropriate soccer-specific fatigue protocol
      (SAFT). Upon completion of the fatigue protocol, subjects were immediately
      retested. Intersession reliability was acceptable and could be considered capable
      of detecting worthwhile changes in performance. Results showed that leg stiffness
      decreased in the U13 year-olds, was maintained in the U15 age group, and
      increased in the U17 players. Contact times and flight times did not change in
      the U13 and U15 year-olds, but significantly decreased and increased,
      respectively, in the U17 age group. The data suggest that age-related changes in
      the neuromuscular control of leg stiffness are present in youth female soccer
      players. Practitioners should be aware of these discrepancies in neuromuscular
      responses to soccer-specific fatigue, and should tailor training programs to meet
      the needs of individuals, which may subsequently enhance performance and reduce
      injury risk.

PMID- 29065080
TI  - Walking Speed, Risk Factors, and Cardiovascular Events in Older Adults-Systematic
      Review.
AB  - Fonseca Alves, DJ, Bartholomeu-Neto, J, Junior, ER, Ribeiro Zarricueta, BS,
      Nobrega, OT, and Cordova, C. Walking speed, risk factors, and cardiovascular
      events in older adults-systematic review. J Strength Cond Res 31(11): 3235-3244,
      2017-It is important that new clinical measures can identify risk factors and
      predict cardiovascular events. Although the walking speed (WS) test is a
      potential candidate, consolidating data from multiple studies is required to
      determine comparative references. We examined the associations of WS measures
      with markers of cardiovascular risk and with cardiovascular events in
      noninstitutionalized subjects older than 60 years. A systematic review of
      observational studies was conducted using MEDLINE and SCOPUS from inception of
      the databases to December 2014, aiming at studies that evaluated WS as the
      primary outcome (usual or maximal pace) within a distance <=20 m associated with
      cardiovascular health. All 15 included studies (29,845 subjects) reported
      significant associations of WS with different cardiovascular risk factors
      (coronary artery calcification, C-reactive protein, hypertension, diabetes, and
      intima-media thickness) and occurrence of cardiovascular events (peripheral
      artery disease, stroke, and mortality). Approximately 80% of the studies used a
      distance <=6 m and WS at usual pace. There was high heterogeneity in the risk
      thresholds established by different studies. Our results suggest usefulness of
      the WS test as a tool for cardiovascular risk stratification in older adults.
      However, the variation in speed thresholds and diversity of protocols among
      studies suggest caution when generalizing results to different older adult
      populations. Because the WS test is a simple, cheap, and safe tool to administer,
      we make suggestions for its standardization in future studies.

PMID- 29065081
TI  - Reply.

PMID- 29065082
TI  - Reply.

PMID- 29065083
TI  - Correspondence.

PMID- 29065084
TI  - Reply.

PMID- 29065086
TI  - Aminoglycoside or Quinolone Ear Drops in the Postoperative Management of
      Tympanoplasty: What Choice Do We Have?

PMID- 29065085
TI  - Resolution of Persistent Post-Stapedotomy Vertigo With Migraine Prophylactic
      Medication.
AB  - OBJECTIVE: To describe persistent post-stapedotomy vertigo (PSV) and its
      treatment using migraine prophylaxis. PATIENTS: A retrospective review of all
      patients with persistent PSV spanning 10 years at a tertiary academic hospital
      was performed. Patients who experienced persistent vertigo for a minimum of 3
      months after surgery were included. Those with possible perilymph fistula, long
      prosthesis, and benign paroxysmal positional vertigo were excluded.
      INTERVENTIONS: All patients received instructions on migraine dietary and
      lifestyle changes and Vitamin B2 and magnesium. In addition, prophylactic
      treatment with nortriptyline, verapamil, or a combination thereof was started.
      MAIN OUTCOME MEASURE: Changes in vertigo frequency was the main outcome variable.
      The secondary outcome variables included the time period and medications
      necessary to achieve symptomatic resolution. RESULTS: Four women and one man with
      an average age of 53 years were identified that met criteria for persistent PSV
      indicating an incidence of 0.9% at our institution. The onset of vertigo symptoms
      was on average 20 days postoperatively. All five patients had daily vertigo
      episodes and experienced complete resolution with no vertigo episodes after
      treatment. Symptomatic resolution was achieved over an average of 9 weeks after
      initiating treatments. CONCLUSIONS: Persistent PSV beyond 3 months is a rare
      occurrence and its treatment can be challenging when there is no evidence of an
      underlying pathology. This subset of patients may be suffering from migraine,
      which was triggered postoperatively. Treatment with migraine prophylaxis in this
      cohort of patients may result in resolution of vertigo.

PMID- 29065087
TI  - Stress and Unusual Events Exacerbate Symptoms in Meniere's Disease: A
      Longitudinal Study.
AB  - HYPOTHESIS: Stress and unusual events are associated with a higher likelihood of
      attacks and increased symptom severity in Meniere's disease (MD). BACKGROUND: MD
      is an unpredictable condition which severely impacts the quality of life of those
      affected. It is thought that unusual activity and stress may act as an attack
      trigger in MD, but research in this area has been limited to date. METHODS: This
      was a longitudinal study conducted over two phases. A mobile phone application
      was used to collect daily data on Meniere's attacks and individual symptoms
      (aural fullness, dizziness, hearing loss, and tinnitus), as well as prevalence of
      unusual events (phase I), and stress levels (phase II). There were 1,031
      participants (730 women, mean age 46.0 yr) in phase I and 695 participants (484
      women, mean age 47.7 yr) in phase II. Panel data regression analyses were
      employed to examine for associations between unusual events/stress and
      attacks/symptoms, including the study of 24 hours lead and lag effects. RESULTS:
      Unusual events and higher stress levels were associated with higher odds of
      Meniere's attacks and more severe symptoms. The odds of experiencing an attack
      were 2.94 (95% confidence interval [CI] 2.37, 3.65) with reporting of unusual
      events and increased by 1.24 (95% CI 1.20, 1.28) per unit increase in stress
      level. Twenty-four hour lead (OR 1.10 [95% CI 1.07, 1.14]) and lag (OR 1.10 [95%
      CI 1.06, 1.13]) effects on attacks were also found with increases in stress.
      CONCLUSION: This study provides the strongest evidence to date that stress and
      unusual events are associated with attacks and symptom exacerbation in MD.
      Improving our understanding of stress and unusual events as triggers in Meniere's
      may reduce the uncertainty associated with this condition and lead to improved
      quality of life for affected individuals.

PMID- 29065088
TI  - Preventing Facial Nerve Stimulation by Triphasic Pulse Stimulation in Cochlear
      Implant Users: Intraoperative Recordings.
AB  - HYPOTHESIS: Triphasic pulse stimulation of the auditory nerve can prevent
      unintended facial nerve stimulation (FNS) due to a different electromyographic
      (EMG) input-output function compared with biphasic pulses. BACKGROUND: FNS is
      sometimes observed in cochlear implant (CI) users as an unpleasant side effect of
      electrical stimulation using biphasic pulse patterns (BPP). Clinical remedies to
      alleviate FNS are 1) to extend stimulus phase duration or 2) to completely
      deactivate the electrode. In some cases, these options do not provide sufficient
      FNS reduction or are detrimental to subject performance. Stimulation using
      triphasic pulse patterns (TPP) has been shown to prevent FNS more effectively,
      yet the underlying mechanism remains unclear. METHODS: EMG potentials of muscles
      innervated by the facial nerve (orbicularis oculi and oris muscles) were recorded
      to quantitatively compare the effect of BPP and TPP stimulation on FNS.
      Recordings were conducted in five subjects during CI surgery. In two exemplary
      cases, different leading phase polarities in alternating and non-alternating
      order were tested. RESULTS: Compared with our previous study in awake patients
      using surface electrodes (Bahmer and Baumann, 2016), intraoperative recordings
      using subdermal electrodes showed lower noise content and allowed higher sampling
      resolution. While inter-subject variation remained high, intra-subject results
      for different electrode positions were comparable: FNS was strongly reduced for
      cathodic-first TPP stimulation. In contrast, exemplary cases showed little
      reduction for anodic-first TPP as well as for alternating stimulation.
      CONCLUSION: FNS in CI users can be reduced using TPP stimulation, but the
      ameliorative effect appears to be dependent on the leading stimulus polarity.

PMID- 29065089
TI  - High Incidence of Bell's Palsy After Mastoidectomy: A Longitudinal Follow-up
      Study.
AB  - OBJECTIVE: The objective of this study was to compare the prevalence of Bell's
      palsy in participants who underwent mastoidectomy (to treat chronic otitis media)
      and nonmastoidectomy participants (control). METHODS: Using the national cohort
      study from the Korean Health Insurance Review and Assessment Service,
      mastoidectomy patients (2,045) and control participants (8,180) were matched 1:4
      for age, sex, income, and region of residence. The prevalence of Bell's palsy in
      both the groups was measured from 0 to 10 years postoperation. RESULTS: In a
      sample of 1,025,340 Korean individuals, 7,070 were diagnosed or treated with
      Bell's palsy between 2002 and 2013; the annual incidence of Bell's palsy was
      0.057%. The overall prevalence of Bell's palsy was three times higher in the
      mastoidectomy group (1.27%) than control group (0.49%) (p < 0.001). The
      prevalence of Bell's palsy was different between the two groups in postoperative
      0 year: 0.78% for the mastoidectomy group versus 0.01% for the control group (p <
      0.001). CONCLUSION: Although we could not verify the laterality, the prevalence
      of Bell's palsy was increased in chronic otitis media patients treated with
      mastoidectomy patients compared with controls, especially within a year after
      surgery.

PMID- 29065090
TI  - Do Measurements of Inner Ear Structures Help in the Diagnosis of Inner Ear
      Malformations? A Review of Literature.
AB  - OBJECTIVE: We conducted an extensive review of the literature relevant to inner
      ear measurements in normal and malformative conditions to select reproducible
      methods and normative ranges that may be used in clinical practice. DATA SOURCES
      AND STUDY SELECTION: A review of the published literature was performed in the
      English language using PubMed with appropriate keywords. We selected only those
      articles containing normative values of inner ear structures. DATA EXTRACTION AND
      DATA SYNTHESIS: The following measurements were identified as reproducible and
      sensitive for the diagnosis of inner malformations: cochlear height in coronal
      plane; maximal diameter of bony island of lateral semicircular canal; width of
      vestibular aqueduct: 1) at midpoint; 2) at operculum in axial plane; cochlear
      canal and cochlear width in multiplanar reconstructions (MPR)/axial; cochlear
      length. The following cutoffs for normal inner ears are proposed based on the
      comparative analysis of the literature: cochlea height: >4.3 mm; lateral
      semicircular canal bony island: >3 mm; vestibular aqueduct: <0.9 (midpoint) and
      <1.9 mm (operculum); cochlear canal (axial MPR): >1.4 mm and <2.5 mm; cochlear
      width (MPR): >5.4 mm. CONCLUSION: Measurements of inner ear structures can help
      in the interpretation of computed tomography images. They increase the
      sensitivity in detecting inner ear malformations, especially cochlear hypoplasia
      now considered more common than previously thought.

PMID- 29065091
TI  - Response to Letter to the Editor: "Comparison of Acyclovir and Famciclovir for
      Ramsay Hunt Syndrome".

PMID- 29065092
TI  - Letter to the Editor Comment on "Ramsay Hunt Syndrome".

PMID- 29065093
TI  - Cochlear Implantation in Cochlear Ossification: Retrospective Review of
      Etiologies, Surgical Considerations, and Auditory Outcomes.
AB  - OBJECTIVES: 1) To review the surgical and auditory outcomes and complications of
      cochlear implantation in cases with cochlear ossification. 2) To evaluate
      association between the extent and etiology of ossification to outcomes. STUDY
      DESIGN: Retrospective study. SETTING: Otology and skull base surgery center.
      SUBJECTS AND METHODS: Charts of 40 patients (42 ears) with cochlear ossification
      undergoing cochlear implantation were reviewed. Demographic features, operative
      findings, auditory outcomes, and complications were analyzed. Operative findings
      included extent of cochlear ossification, extent of drilling required to obtain
      patent cochlear lumen, approach (posterior tympanotomy/subtotal petrosectomy),
      electrode insertion (partial/complete, scala tympani/vestibuli), and
      complications. Auditory outcomes were assessed over a 4-year follow-up period
      using vowel, word, sentence, and comprehension scores. Patients were divided into
      groups (otosclerotic/non-otosclerotic and round window/basal turn ossification)
      for comparison of auditory outcomes. Outcomes were compared with 60 randomly
      identified controls (adults with postlingual deafness) who underwent implantation
      with no cochlear ossification. RESULTS: The median age and duration of deafness
      of patients was 54.39 and 27.15 years, respectively. Etiology of cochlear
      ossification was otosclerosis in 23 of 42 ears and mixed in 19 of 42 ears
      (chronic otitis media, temporal bone fractures, idiopathic, meningitis, Cogan's
      syndrome) with exclusive round window involvement in 54.7% of cases and the rest
      having partial or complete basal turn ossification. 59.5% ears underwent subtotal
      petrosectomy for implantation. Three patients underwent scala vestibuli insertion
      and five had incomplete electrode insertion. Auditory outcomes were comparable in
      otosclerotic and non-otosclerotic cases and in round window and basal turn
      ossification cases. No significant differences were observed in auditory scores
      when compared with controls with no ossification. CONCLUSIONS: Cochlear
      implantation in cochlear ossification is feasible despite surgical challenges and
      modifications. Auditory outcomes in basal turn ossification appear to be
      comparable to cases with no ossification with extent of ossification having no
      significant association with outcomes.

PMID- 29065094
TI  - The Growing-and Now Alarming-Burden of Hearing Loss Worldwide.

PMID- 29065095
TI  - Cochlear Implant Associated Labyrinthitis: A Previously Unrecognized Phenomenon
      With a Distinct Clinical and Electrophysiological Impedance Pattern.
AB  - OBJECTIVES: To report a unique clinical entity "cochlear implant associated
      labyrinthitis," characterized by a distinct constellation of clinical symptoms
      and pattern of electrode impedance fluctuations. STUDY DESIGN: Retrospective
      chart review. METHODS: All patients that underwent cochlear implantation between
      January 2014 and December 2016 were retrospectively reviewed. All subjects with
      acute onset dizziness, device performance decline, and characteristic erratic
      pattern of electrode impedances occurring after an asymptotic postoperative
      interval were identified and reported. RESULTS: Five patients with the above
      criteria were identified, representing 1.4% of all implant surgeries performed
      during this time. The median age at time of implantation was 71 years, and the
      median time interval between implantation and onset of symptoms was 126 days. All
      patients exhibited acute onset dizziness, subjective performance deterioration,
      erratic impedance pattern, and two experienced worsening tinnitus. Two of five
      patients underwent subsequent CT imaging, where good electrode placement was
      confirmed without cochlear ossification. Two of five patients received oral
      prednisone therapy. All patients reported a subjective improvement in symptoms
      and stabilization of electrode impedances. Three patients subsequently received
      vestibular testing, where significantly reduced peripheral vestibular function
      was identified. CONCLUSIONS: We describe a unique clinical entity, "cochlear
      implant associated labyrinthitis," characterized by a distinct constellation of
      clinical symptoms and corresponding electrode impedance anomalies. The exact
      cause for this event remains unknown, but may be related to viral illness,
      delayed foreign body reaction to the electrode, or a reaction to electrical
      stimulation. Future studies characterizing this unique clinical entity are needed
      to further elucidate cause and optimal management.

PMID- 29065096
TI  - Changes in Serum Prestin Concentration After Exposure to Cisplatin.
AB  - HYPOTHESIS: There are temporal changes in the outer-hair-cell-specific protein,
      prestin, in the blood after administration of low-dose cisplatin. METHODS: Two
      rodent models of ototoxicity were used. After control and baseline data
      collection, mice (n = 30) and guinea pigs (n = 10), respectively, were treated
      with cisplatin at 8 mg/kg. Auditory brainstem responses were recorded on Days 1,
      3, 7, and 14 after treatment. Five mice were sacrificed at each time point and
      serum samples were obtained. A group of 10 guinea pigs were tested and serum
      samples were collected at each time point. Serum prestin concentrations were
      measured using separate enzyme-linked immunosorbent assays for each species.
      RESULTS: Auditory brainstem responses thresholds changed relatively little in
      mice, but gradually increased in guinea pigs, as a function of time after
      cisplatin exposure. In contrast, serum prestin concentrations rose, reaching a
      peak on Days 3 and 7 after cisplatin treatment in mouse and guinea pig,
      respectively, before declining back to or below baseline/control levels 14 days
      after treatment. CONCLUSION: There was a time-dependent pattern of change in
      serum prestin after exposure to low-dose cisplatin in a resistant (mouse) and
      sensitive (guinea pig) rodent models. These comparative results suggest prestin
      may serve as a biomarker for cisplatin ototoxicity.

PMID- 29065097
TI  - Morphological Characteristics of Osseous External Auditory Canal and Its
      Relationship With External Auditory Canal Cholesteatoma in Patients With
      Congenital Aural Stenosis.
AB  - OBJECTIVE: To investigate the characteristics of stenotic external auditory canal
      (EAC) (e.g., shape, length, orientation, and curvature) and to compare them with
      those of the cholesteatoma and no cholesteatoma groups, which may help to explain
      cholesteatoma formation to a certain degree. METHODS: Computed tomography scans
      of two groups of patients (with and without EAC cholesteatoma) were analyzed. We
      determined the degree of microtia, the stenosis of EAC, radius and curvature of
      osseous EAC bending (abbreviated as OEB-r and OEB-c, respectively), and other
      anatomic parameters of EAC by using Mimics and Matlab. RESULTS: There was no
      significant difference in the degree of microtia between the cholesteatoma and no
      cholesteatoma groups using the Marx grading system. Additionally, no significant
      difference was found in the stenosis of EAC between the two groups. The OEB-r was
      smaller in the cholesteatoma group (4.62 +/- 0.62 mm) than in the no
      cholesteatoma group (7.41 +/- 0.50 mm), and the OEB-c was found to be larger in
      the cholesteatoma group (1.55 +/- 0.05 * 10 mm) than in the no cholesteatoma
      group (1.10 +/- 0.10 * 10 mm). Moreover, the OEB-c (OR, 8.60; 95% CI, 2.67-27.75)
      was associated with EAC cholesteatoma formation. CONCLUSION: The curvature of
      osseous EAC in the cholesteatoma group was significantly larger than that in the
      no cholesteatoma group. It is suggested that the curvature of osseous EAC was a
      risk factor for EAC cholesteatoma formation.

PMID- 29065098
TI  - Effects of sodium nitrite on renal function and blood pressure in hypertensive
      vs. healthy study participants: a randomized, placebo-controlled, crossover
      study.
AB  - OBJECTIVE: Nitric oxide is a key player in regulating vascular tone. Impaired
      endothelial nitric oxide synthesis plays an important role in hypertension.
      Replenishing of nitric oxide by sodium nitrite (NaNO2) has not been investigated
      in patients with essential hypertension (EHT). We aimed to determine the effects
      of NaNO2 on blood pressure (BP) and renal sodium and water regulation in patients
      with EHT compared with healthy control study participants (CON). METHODS: In a
      placebo-controlled, crossover study, we infused 240 MUg NaNO2/kg/h or isotonic
      saline for 2 h in 14 EHT and 14 CON. During infusion, we measured changes in
      brachial and central BP, free water clearance, fractional sodium excretion, and
      urinary excretion rate of gamma-subunit of the epithelial sodium channel (U
      ENaCgamma), and aquaporin-2 (U-AQP2). RESULTS: Placebo-adjusted brachial SBP
      decreased 18 mmHg (P < 0.001) during NaNO2 infusion in EHT and 12 mmHg (P <
      0.001) in CON (Pbetween = 0.024). Brachial DBP and central SBP decreased equally
      in both groups during NaNO2. In EHT, we found a decrease in U-ENaCgamma during
      NaNO2 infusion. In both groups, we observed a decrease in fractional sodium
      excretion, free water clearance, and U-AQP2 during NaNO2 infusion. CONCLUSION:
      This study demonstrated an augmented BP-lowering effect of NaNO2 in patients with
      EHT. We observed an antinatriuretic and antidiuretic effect of NaNO2 in both
      groups, and a decrease in U-ENaCgamma, solely in EHT. In both groups, we detected
      a nonvasopressin mediated decrease in U-AQP2, which is most likely compensatory
      to the decline in diuresis.

PMID- 29065100
TI  - Primary sarcoma of the heart.

PMID- 29065099
TI  - An unexpected cause of acute intestinal obstruction: the major role of imaging.

PMID- 29065101
TI  - Need for more action when young hearts are broken.

PMID- 29065102
TI  - The Function of the Novel Mechanical Activated Ion Channel Piezo1 in the Human
      Osteosarcoma Cells.
AB  - BACKGROUND The Piezo1 protein ion channel is a novel mechanical activated ion
      channel which is related to mechanical signal transduction. However, the function
      of the mechanically activated ion channel Piezo1 had not been explored. In this
      study, we explored the function of the Piezo1 ion channel in human osteosarcoma
      (OS) cells related to apoptosis, invasion, and the cell proliferation. MATERIAL
      AND METHODS Reverse transcription polymerase chain reaction (RT-PCR) and western
      blotting were used to detect the expression of the Piezo1 protein. CCK-8,
      Transwell experiments and AV-PI were used to detected cell proliferation, cell
      invasion and cell apoptosis. RESULTS The Piezo1 protein ion channel was highly
      expressed in human OS cells. The Piezo1-shRNA inhibited the expression of the
      Piezo1. We explored whether LV3-PIEZO1-homo-3201 could act as Piezo1-shRNA, which
      could then be an inhibitor of Piezo1. The expression of Piezo1 in the 2-hour
      stretch group were slightly higher than the 0-hour stretch group, and the
      difference was not statistically significant (n=3, p>0.05, one-way ANOVA). The
      apoptotic gene such as the Bax, BAD, caspase-3, and caspase-9 had the same
      characteristics as the Piezo1 expression under the stretch force. We also
      explored the invasion of Piezo1 in vivo using nude mice, and found that Piezo1
      shRNA could inhibit the invasion of the OS cells. CONCLUSIONS The Piezo1 protein
      may be a novel, potential therapeutic target for OS.

PMID- 29065103
TI  - Family history of cancer in children and adolescents with germ cell tumours: a
      report from the Children's Oncology Group.
AB  - BACKGROUND: Studies of family history of cancer in paediatric germ cell tumours
      (GCTs) are few, and none has had sufficient sample size to specifically evaluate
      family history of GCT. METHODS: We utilised family history data from a paediatric
      GCT study to calculate standardised incidence ratios (SIR) for GCT and other
      cancers using age- and sex-specific incidence rates from the SEER Program.
      RESULTS: This analysis included 7998 relatives of paediatric GCT probands. We
      observed a higher number of GCT cases than expected in male and female relatives
      of probands (SIR=2.38, 95% CI 1.25, 3.51 for males; SIR=14.3, 95% CI 0.29, 28.4
      for females). Further, we observed a particularly strong SIR for relatives of
      probands with intracranial GCT (SIR=8.07, 95% CI 3.51, 12.6). The SIR for
      relatives of probands with ovarian GCT was also elevated but did not reach
      statistical significance (SIR 4.35, 95% CI 0-9.27). Other notable associations
      include elevated SIRs for melanoma in male relatives and reduced SIRs for
      lymphatic/haematologic malignancies in male and female relatives. CONCLUSIONS:
      These results support the hypothesis that familial aggregation of GCT occurs in
      males and females.

PMID- 29065104
TI  - Systemic therapies for recurrent or metastatic nasopharyngeal carcinoma: a
      systematic review.
AB  - BACKGROUND: The majority of published studies in recurrent or metastatic
      nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of
      progression-free survival (PFS) and overall survival (OS) outcomes, therefore, is
      difficult. This study aim to analyse existent literature to estimate the relative
      efficacy of available systemic regimens in RM-NPC, as well as provide estimates
      of aggregate OS and PFS. METHODS: We conducted a systematic search of MEDLINE,
      EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only)
      investigating cytotoxic and molecularly targeted agents in adult patients with RM
      NPC were included. All relevant studies were assessed for quality using Downs and
      Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and
      Student's t-test were performed for all identified studies (model A). For studies
      that published analysable Kaplan-Meier curves, survival data were extracted and
      marginal proportional hazards models were constructed (model B). RESULTS: A total
      of 56 studies were identified and included in model A, 26 of which had analysable
      Kaplan-Meier curves and were included in model B. The 26 studies in model B had
      significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7,
      P=0.002). For patients receiving first line chemotherapy, the estimated median OS
      was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95%
      CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+),
      the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5
      months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first
      line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by
      model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting,
      the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by
      model B (95% CI, 4.7-5.6). CONCLUSIONS: We present the first aggregate estimates
      of OS and PFS for RM-NPC patients receiving first and second-line or higher
      treatment settings, which could inform the design of future clinical trials in
      this disease setting.

PMID- 29065105
TI  - A systematic review and meta-analysis of the association between childhood
      infections and the risk of childhood acute lymphoblastic leukaemia.
AB  - BACKGROUND: To determine whether childhood infections were associated with the
      development of childhood acute lymphoblastic leukaemia (ALL). METHODS: We
      included studies that assessed any infection in childhood prior to the diagnosis
      of ALL in children aged 0-19 years compared to children without cancer. The
      primary analysis synthesised any infection against the odds of ALL, and secondary
      analyses assessed the frequency, severity, timing of infections, and specific
      infectious agents against the odds of ALL. Subgroup analyses by data source were
      investigated. RESULTS: In our primary analysis of 12 496 children with ALL and 2
      356 288 children without ALL from 38 studies, we found that any infection was not
      associated with ALL (odds ratio (OR)=1.10, 95% CI: 0.95-1.28). Among studies with
      laboratory-confirmed infections, the presence of infections increased the odds of
      ALL by 2.4-fold (OR=2.42, 95% CI: 1.54-3.82). Frequency, severity, and timing of
      infection were not associated with ALL. CONCLUSIONS: The hypothesis put forward
      by Greaves and others about an infectious aetiology are neither confirmed nor
      refuted and the overall evidence remains inadequate for good judgement. The
      qualitative difference in the subgroup effects require further study, and future
      research will need to address the challenges in measuring infectious exposures.

PMID- 29065106
TI  - Dual roles of tumour cells-derived matrix metalloproteinase 2 on brain tumour
      growth and invasion.
AB  - BACKGROUND: A previous study on a murine astrocytoma cell-line ALTS1C1 showed a
      highly invasive pattern similar to clinical anaplastic astrocytoma in vivo. This
      cell-line also expressed a high level of matrix metalloproteinase 2 (MMP2). This
      study aimed to verify the role of MMP2 in brain tumour progression. METHODS:
      ALTS1C1 and MMP2 knockdown (MMP2kd) cells were inoculated intracranially, and
      tumour microenvironment was assessed by immunohistochemistry staining. RESULTS:
      MMP2 expression was co-localised with CD31-positive cells at invading the tumour
      front and correlated with an invasive marker GLUT-1. The suppression of MMP2
      expression prolonged the survival of tumour-bearing mice associated with tumours
      having smoother tumour margins, decreased Ki67-proliferating index, and down
      regulated GLUT-1 antigen. Although the reduction of MMP2 expression did not alter
      the vessel density in comparison to parental ALTS1C1 tumours, vessels in MMP2kd
      tumours were less functional, as evidenced by the low ratio of pericyte coverage
      and reduction in Hoechst33342 dye perfusion. CONCLUSIONS: This study illustrated
      that tumour-derived MMP2 has at least two roles in tumour malignancy; to enhance
      tumour invasiveness by degrading the extracellular matrix and to enhance tumour
      growth by promoting vessel maturation and function.

PMID- 29065107
TI  - TAMeless traitors: macrophages in cancer progression and metastasis.
AB  - Macrophages are conventionally classified into M1 and M2 subtypes according to
      their differentiation status and functional role in the immune system. However,
      accumulating evidence suggests that this binary classification system is
      insufficient to account for the remarkable plasticity of macrophages that gives
      rise to an immense diversity of subtypes. This diverse spectrum of macrophage
      subtypes play critical roles in various homeostatic and immune functions, but
      remain far from being fully characterised. In addition to their roles in normal
      physiological conditions, macrophages also play crucial roles in disease
      conditions such as cancer. In this review, we discuss the roles tumour-associated
      macrophages (TAMs) play in regulating different steps of tumour progression and
      metastasis, and the opportunities to target them in the quest for cancer
      prevention and treatment.

PMID- 29065109
TI  - Risk stratification of childhood cancer survivors necessary for evidence-based
      clinical long-term follow-up.
AB  - BACKGROUND: Reorganisation of clinical follow-up care in England was proposed by
      the National Cancer Survivorship Initiative (NCSI), based on cancer type and
      treatment, ranging from Level 1 (supported self-management) to Level 3
      (consultant-led care). The objective of this study was to provide an
      investigation of the risks of serious adverse health-outcomes associated with
      NCSI Levels of clinical care using a large population-based cohort of childhood
      cancer survivors. METHODS: The British Childhood Cancer Survivor Study (BCCSS)
      was used to investigate risks of specific causes of death, subsequent primary
      neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. RESULTS:
      Cumulative (excess) risks of specified adverse outcomes by 45 years from
      diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were
      for: SPNs-5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold
      expected); non-neoplastic death-2% (two-fold expected), 4% (three-fold expected)
      and 8% (seven-fold expected); non-fatal non-neoplastic condition-14%, 27% and
      40%, respectively. Consequently overall cumulative risks of any adverse health
      outcome were 21%, 45% and 69%, respectively. CONCLUSIONS: Despite its simplicity
      the risk stratification tool provides clear and strong discrimination between
      survivors assigned to different NCSI Levels in terms of long-term cumulative and
      excess risks of serious adverse outcomes.

PMID- 29065108
TI  - Towards gene- and gender-based risk estimates in Lynch syndrome; age-specific
      incidences for 13 extra-colorectal cancer types.
AB  - BACKGROUND: In Lynch syndrome, inherited mismatch repair (MMR) defects predispose
      to colorectal cancer and to a wide spectrum of extra-colorectal tumours.
      Utilising a cohort study design, we aimed to determine the risk of extra
      colorectal cancer and to identify yet unrecognised tumour types. METHODS: Data
      from 1624 Lynch syndrome mutation carriers in the Danish hereditary non-polyposis
      colorectal cancer register were used to estimate the sex- and age-specific
      incidence rate ratios (IRRs) for 30 extra-colorectal malignancies with comparison
      to the general population. RESULTS: Significantly increased IRRs were identified
      for 13 cancer types with differences related to gender, age and disease
      predisposing gene. The different cancer types showed variable peak age incidence
      rates (IRs) with the highest IRs for ovarian cancer at age 30-49 years, for
      endometrial cancer, breast cancer, renal cell cancer and brain tumours at age 50
      69 years, and for urothelial cancer, small bowel cancer, gastric cancer,
      pancreatic cancer and skin tumours after age 70. CONCLUSIONS: The broad spectrum
      of tumour types that develop at an increased incidence defines Lynch syndrome as
      a multi-tumour syndrome. The variable incidences in relation to age, gender and
      gene suggest a need for individualised surveillance.

PMID- 29065110
TI  - Antibody drug conjugates and bystander killing: is antigen-dependent
      internalisation required?
AB  - Antibody drug conjugates (ADCs) employ the exquisite specificity of tumour
      specific monoclonal antibodies (mAb) for the targeted delivery of highly potent
      cytotoxic drugs to the tumour site. The chemistry of the linker, which connects
      the drug to the mAb, determines how and when the drug is released from the mAb.
      This, as well as the chemistry of the drug, can dictate whether the drug can
      diffuse into surrounding cells, resulting in 'bystander killing'. Initially, any
      bystander killing mechanism of action of an ADC was understood to involve an
      essential sequence of steps beginning with surface antigen targeting,
      internalisation, intracellular linker cleavage, drug release, and diffusion of
      drug away from the targeted cell. However, recent studies indicate that,
      depending on the linker and drug combination, this mechanism may not be essential
      and ADCs can be cleaved extracellularly or via other mechanisms. In this
      minireview, we will examine the role of bystander killing by ADCs and explore the
      emerging evidence of how this can occur independently of internalisation.

PMID- 29065111
TI  - Identification of a specific peptide binding to colon cancer cells from a phage
      displayed peptide library.
AB  - BACKGROUND: New molecular probes are essential for early colon cancer diagnosis.
      A phage-display screening was performed to select novel binding peptides for
      early colon cancer imaging detection. METHODS: A human colon cancer cell line
      (COLO320HSR) and a normal human intestinal epithelial cell line (NCM460) were
      used for subtractive screening with a phage peptide library. The positive
      peptides were identified, and their binding capacities were confirmed by confocal
      immunofluorescence both in human colon cancer cells and in biopsy specimens. The
      sequences were further analysed for homology and the existing mimotopes by the
      BLAST algorithm and the MimoDB database. RESULTS: A peptide termed as CBP-DWS,
      which was demonstrated to be capable of binding to a panel of human colon cancer
      cell lines and tissues, was identified; it had virtually no binding to normal
      human intestinal epithelial cell line NCM460 and normal surrounding colon
      tissues. Bioinformatics analyses suggest that CBP-DWS targets human Glypican-3,
      which may be involved in important cellular functions in multiple cancer types.
      CONCLUSIONS: These studies suggest that the selected peptide CBP-DWS may be a
      candidate to serve as a novel probe for colon cancer imaging.

PMID- 29065112
TI  - Analytical equation for outflow along the flow in a perforated fluid distribution
      pipe.
AB  - Perforated fluid distribution pipes have been widely used in agriculture, water
      supply and drainage, ventilation, the chemical industry, and other sectors. The
      momentum equation for variable mass flow with a variable exchange coefficient and
      variable friction coefficient was developed by using the momentum conservation
      method under the condition of a certain slope. The change laws of the variable
      momentum exchange coefficient and the variable resistance coefficient along the
      flow were analyzed, and the function of the momentum exchange coefficient was
      given. According to the velocity distribution of the power function, the momentum
      equation of variable mass flow was solved for different Reynolds numbers. The
      analytical solution contains components of pressure, gravity, friction and
      momentum and reflects the influence of various factors on the pressure
      distribution along the perforated pipe. The calculated results of the analytical
      solution were compared with the experimental values of the study by Jin et al.
      1984 and Wang et al. 2001 with the mean errors 8.2%, 3.8% and 2.7%, and showed
      that the analytical solution of the variable mass momentum equation was
      qualitatively and quantitatively consistent with the experimental results.

PMID- 29065113
TI  - Identification of immune signatures predictive of clinical protection from
      malaria.
AB  - Antibodies are thought to play an essential role in naturally acquired immunity
      to malaria. Prospective cohort studies have frequently shown how continuous
      exposure to the malaria parasite Plasmodium falciparum cause an accumulation of
      specific responses against various antigens that correlate with a decreased risk
      of clinical malaria episodes. However, small effect sizes and the often
      polymorphic nature of immunogenic parasite proteins make the robust
      identification of the true targets of protective immunity ambiguous. Furthermore,
      the degree of individual-level protection conferred by elevated responses to
      these antigens has not yet been explored. Here we applied a machine learning
      approach to identify immune signatures predictive of individual-level protection
      against clinical disease. We find that commonly assumed immune correlates are
      poor predictors of clinical protection in children. On the other hand, antibody
      profiles predictive of an individual's malaria protective status can be found in
      data comprising responses to a large set of diverse parasite proteins. We show
      that this pattern emerges only after years of continuous exposure to the malaria
      parasite, whereas susceptibility to clinical episodes in young hosts (< 10 years)
      cannot be ascertained by measured antibody responses alone.

PMID- 29065114
TI  - Global genotype flow in Cercospora beticola populations confirmed through
      genotyping-by-sequencing.
AB  - Genotyping-by-sequencing (GBS) was conducted on 333 Cercospora isolates collected
      from Beta vulgaris (sugar beet, table beet and swiss chard) in the USA and
      Europe. Cercospora beticola was confirmed as the species predominantly isolated
      from leaves with Cercospora leaf spot (CLS) symptoms. However, C. cf. flagellaris
      also was detected at a frequency of 3% in two table beet fields in New York.
      Resolution of the spatial structure and identification of clonal lineages in C.
      beticola populations using genome-wide single nucleotide polymorphisms (SNPs)
      obtained from GBS was compared to genotyping using microsatellites. Varying
      distance thresholds (bitwise distance = 0, 1.854599 * 10-4, and 1.298 * 10-3)
      were used for delineation of clonal lineages in C. beticola populations. Results
      supported previous reports of long distance dispersal of C. beticola through
      genotype flow. The GBS-SNP data set provided higher resolution in discriminating
      clonal lineages; however, genotype identification was impacted by filtering
      parameters and the distance threshold at which the multi-locus genotypes (MLGs)
      were contracted to multi-locus lineages. The type of marker or different
      filtering strategies did not impact estimates of population differentiation and
      structure. Results emphasize the importance of robust filtering strategies and
      designation of distance thresholds for delineating clonal lineages in population
      genomics analyses that depend on individual assignment and identification of
      clonal lineages. Detection of recurrent clonal lineages shared between the USA
      and Europe, even in the relaxed-filtered SNP data set and with a conservative
      distance threshold for contraction of MLGs, provided strong evidence for global
      genotype flow in C. beticola populations. The implications of intercontinental
      migration in C. beticola populations for CLS management are discussed.

PMID- 29065115
TI  - Seroprevalence and disease burden of acute hepatitis A in adult population in
      South Korea.
AB  - BACKGROUND: Adult seroprevalence of HAV is decreasing in developed countries
      including South Korea, due to general sanitation improvement. Although hepatitis
      A vaccination was introduced in South Korea more than 20 years ago, recent
      infection rates have not decreased. In this study, we investigate the
      seroprevalence of anti-HAV IgG, and estimate the national disease burden of acute
      hepatitis A in adult population. METHODS: Seroprevalence data were collected from
      health promotion center of Korea University Guro Hospital, in Seoul, Korea from
      2010 to 2014. Data from adults (>=20-years) being tested for anti-HAV IgG were
      included. In addition, epidemiological and clinical data of patients diagnosed
      with acute hepatitis A from 2009 to 2013, were collected from Korean Statistical
      Information Service (KOSIS) and the National Health Insurance Service (NHIS)
      database. Data were stratified and compared by age groups. RESULTS: A total of
      11,177 subjects were tested for anti-HAV IgG from 2010 to 2014. Age-related
      seroprevalence showed relatively low seropositivity in young adults. Incidence of
      acute hepatitis A was highest in 2009 and lowest in 2013. When categorized by age
      group, adults in their 20s and 30s had more HAV infections and related-admissions
      than older adults. However, ICU admission rate and average insurance-covered cost
      was high in older adults. CONCLUSION: The anti-HAV IgG seropositivity in Korean
      younger adult population was low while the incidence of acute hepatitis A was
      high, especially in the 20-39 aged. However, a substantial number of older adults
      were infected, and required more intensive procedures and incurred higher
      insurance-covered medical costs.

PMID- 29065116
TI  - Serum IGF-1 is associated with cognitive functions in early, drug-naive
      Parkinson's disease.
AB  - OBJECTIVE: Cognitive deficits are common in Parkinson's disease (PD) since the
      early stages and many patients eventually develop dementia. Yet, occurrence of
      dementia in PD is unpredictable. Evidence supports the hypothesis that insulin
      like growth factor-1 (IGF-1) is involved in cognitive deficits. Our aim was to
      evaluate the relationship between serum IGF-1 levels and neuropsychological
      scores in a large cohort of drug-naive PD patients during the earliest stages of
      the disease. METHODS: Serum IGF-1 levels were determined in 405 early, drug-naive
      PD patients and 191 healthy controls (HC) enrolled in the Parkinson's Progression
      Markers Initiative (PPMI). The association between serum IGF-1 levels and
      neuropsychological scores was evaluated with linear regression analysis. RESULTS:
      IGF-1 levels were similar in PD and HC. In PD patients the lowest IGF-1 quartile
      was a predictor of lower performances at the Semantic Fluency task (beta = -3.46,
      95%CI: -5.87 to -1.01, p = 0.005), the Symbol Digit Modalities Score (beta = 
      2.09, 95%CI: -4.02 to -0.15, p = 0.034), and Hopkins Verbal Learning Test
      Retention (beta = -0.05, 95%CI: -0.09 to -0.009, p = 0.019). CONCLUSIONS: Lower
      serum IGF-1 levels are associated to poor performances in cognitive tasks
      assessing executive function, attention and verbal memory in a large cohort of
      early PD patients. Follow-up studies are warranted to assess if IGF-1 is related
      to the development of dementia in PD.

PMID- 29065117
TI  - Correction: mlh3 mutations in baker's yeast alter meiotic recombination outcomes
      by increasing noncrossover events genome-wide.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006974.].

PMID- 29065118
TI  - A fresh look at polymicrobial bloodstream infection in cancer patients.
AB  - OBJECTIVES: To assess the current incidence, clinical features, risk factors,
      aetiology, antimicrobial resistance and outcomes of polymicrobial bloodstream
      infection (PBSI) in patients with cancer. METHODS: All prospectively collected
      episodes of PBSI in hospitalised patients were compared with episodes of
      monomicrobial bloodstream infection (MBSI) between 2006 and 2015. RESULTS: We
      identified 194 (10.2%) episodes of PBSI and 1702 MBSI (89.8%). The presence of
      cholangitis, biliary stenting, neutropenia, corticosteroids, neutropenic
      enterocolitis and other abdominal infections were identified as risk factors for
      PBSI. Overall, Gram-negative organisms were the most frequent aetiology, but
      Enterococcus spp. were especially frequent causes of Gram-positive PBSI (30.8%).
      Multidrug-resistant (MDR) organisms were more commonly found in PBSI than in MBSI
      (20.6% vs 12.9%; p = 0.003). Compared to patients with MBSI, those with PBSI
      presented with higher early (15% vs 1.4%; p = 0.04) and overall (32% vs 20.9%;
      p<0.001) case-fatality rates. Risk factors for overall case-fatality were a high
      risk MASCC (Multinational Association of Supportive Care in Cancer) index score,
      corticosteroid use, persistent bacteraemia and septic shock. CONCLUSIONS: PBSI is
      a frequent complication in patients with cancer and is responsible for high
      mortality rates. Physicians should identify patients at risk for PBSI and provide
      empiric antibiotic therapy that covers the most frequent pathogens involved in
      these infections, including MDR strains.

PMID- 29065119
TI  - The quality-of-life burden of knee osteoarthritis in New Zealand adults: A model
      based evaluation.
AB  - BACKGROUND: Knee osteoarthritis is a leading global cause of health-related
      quality of life loss. The aim of this project was to quantify health losses
      arising from knee osteoarthritis in New Zealand (NZ) in terms of quality-adjusted
      life years (QALYs) lost. METHODS: The Osteoarthritis Policy Model (OAPol), a
      validated Monte Carlo computer simulation model, was used to estimate QALYs lost
      due to knee osteoarthritis in the NZ adult population aged 40-84 over their
      lifetimes from the base year of 2006 until death. Data were from the NZ Health
      Survey, NZ Burden of Diseases, NZ Census, and relevant literature. QALYs were
      derived from NZ EQ-5D value set 2. Sensitivity to health state valuation, disease
      and pain prevalence were assessed in secondary analyses. RESULTS: Based on NZ EQ
      5D health state valuations, mean health losses due to knee osteoarthritis over
      people's lifetimes in NZ are 3.44 QALYs per person, corresponding to 467,240
      QALYs across the adult population. Average estimated per person QALY losses are
      higher for non-Maori females (3.55) than Maori females (3.38), and higher for non
      Maori males (3.34) than Maori males (2.60). The proportion of QALYs lost out of
      the total quality-adjusted life expectancy for those without knee osteoarthritis
      is similar across all subgroups, ranging from 20 to 23 percent. CONCLUSIONS: At
      both the individual and population levels, knee osteoarthritis is responsible for
      large lifetime QALY losses. QALY losses are higher for females than males due to
      greater prevalence of knee osteoarthritis and higher life expectancy, and lower
      for Maori than non-Maori due to lower life expectancy. Large health gains are
      potentially realisable from public health and policy measures aimed at decreasing
      incidence, progression, pain, and disability of osteoarthritis.

PMID- 29065120
TI  - Neural field model to reconcile structure with function in primary visual cortex.
AB  - Voltage-sensitive dye imaging experiments in primary visual cortex (V1) have
      shown that local, oriented visual stimuli elicit stable orientation-selective
      activation within the stimulus retinotopic footprint. The cortical activation
      dynamically extends far beyond the retinotopic footprint, but the peripheral
      spread stays non-selective-a surprising finding given a number of anatomo
      functional studies showing the orientation specificity of long-range connections.
      Here we use a computational model to investigate this apparent discrepancy by
      studying the expected population response using known published anatomical
      constraints. The dynamics of input-driven localized states were simulated in a
      planar neural field model with multiple sub-populations encoding orientation. The
      realistic connectivity profile has parameters controlling the clustering of long
      range connections and their orientation bias. We found substantial overlap
      between the anatomically relevant parameter range and a steep decay in
      orientation selective activation that is consistent with the imaging experiments.
      In this way our study reconciles the reported orientation bias of long-range
      connections with the functional expression of orientation selective neural
      activity. Our results demonstrate this sharp decay is contingent on three
      factors, that long-range connections are sufficiently diffuse, that the
      orientation bias of these connections is in an intermediate range (consistent
      with anatomy) and that excitation is sufficiently balanced by inhibition.
      Conversely, our modelling results predict that, for reduced inhibition strength,
      spurious orientation selective activation could be generated through long-range
      lateral connections. Furthermore, if the orientation bias of lateral connections
      is very strong, or if inhibition is particularly weak, the network operates close
      to an instability leading to unbounded cortical activation.

PMID- 29065121
TI  - Is routine ophthalmoscopy really necessary in candidemic patients?
AB  - The purpose of this study was to determine among patients with candidemia the
      real rate of ophthalmoscopy and the impact of performing ocular assessment on the
      outcome of the disease. We performed a post hoc analysis of a prospective,
      multicenter, population-based candidemia surveillance program implemented in
      Spain during 2010-2011 (CANDIPOP). Ophthalmoscopy was performed in only 168 of
      the 365 patients with candidemia (46%). Ocular lesions related to candidemia were
      found in only 13/168 patients (7.7%), of whom 1 reported ocular symptoms
      (incidence of symptomatic disease in the whole population, 0.27% [1/365]).
      Ophthalmological findings led to a change in antifungal therapy in only 5.9% of
      cases (10/168), and performance of the test was not related to a better outcome.
      Ocular candidiasis was not associated with a worse outcome and progressed
      favorably in all but 1 evaluable patient, who did not experience vision loss. The
      low frequency of ophthalmoscopy and ocular involvement and the asymptomatic
      nature of ocular candidiasis, with a favorable outcome in almost all cases, lead
      us to reconsider the need for systematic ophthalmoscopy in all candidemic
      patients.

PMID- 29065122
TI  - Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend
      towards resistance over time.
AB  - Treatment with broadly neutralizing antibodies (bNAbs) has proven effective
      against HIV-1 infections in humanized mice, non-human primates, and humans. Due
      to the high mutation rate of HIV-1, resistance testing of the patient's viral
      strains to the bNAbs is still inevitable. So far, bNAb resistance can only be
      tested in expensive and time-consuming neutralization experiments. Here, we
      introduce well-performing computational models that predict the neutralization
      response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using
      non-linear support vector machines based on a string kernel, the models learnt
      even the important binding sites of bNAbs with more complex epitopes, i.e., the
      CD4 binding site targeting bNAbs, proving thereby the biological relevance of the
      models. To increase the interpretability of the models, we additionally provide a
      new kind of motif logo for each query sequence, visualizing those residues of the
      test sequence that influenced the prediction outcome the most. Moreover, we
      predicted the neutralization sensitivity of around 34,000 HIV-1 samples from
      different time points to a broad range of bNAbs, enabling the first analysis of
      HIV resistance to bNAbs on a global scale. The analysis showed for many of the
      bNAbs a trend towards antibody resistance over time, which had previously only
      been discovered for a small non-representative subset of the global HIV-1
      population.

PMID- 29065123
TI  - Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic
      shock preserves renal mitochondrial function.
AB  - Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays
      a vital role in maintaining vasomotor tone during acute blood loss. We
      hypothesized that decompensated hemorrhagic shock is associated with decreased
      AVP stores and supplementation during resuscitation would improve both blood
      pressure and renal function. Using a decompensated hemorrhagic shock model, male
      Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and
      maintained until the MAP could not be sustained without fluid. Once 40% of the
      shed volume was returned in lactated Ringer's (Severe Shock), animals were
      resuscitated over 60 minutes with 4x the shed volume in lactated Ringer's (LR) or
      the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6
      9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following
      resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with
      AVP). Blood samples were taken to measure AVP levels and renal function.
      Pituitaries were harvested and assayed for AVP. Kidney samples were taken to
      assess mitochondrial function, histology, and oxidative damage. Baseline
      pituitary AVP stores (30,364 +/- 5311 pg/mg) decreased with severe shock and were
      significantly depressed post-resuscitation (13,910 +/- 3016 pg/ml. p<0.05) and at
      18hr (15,592 +/-1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher
      serum AVP levels at 60R (31+/-8 vs 79+/-12; p<0.01) with an improved MAP both at
      60R (125+/-3 vs 77+/-7mmHg; p<0.01) and 18hr (82+/-6 vs 69+/-5mmHg;p<0.05). AVP
      supplementation preserved complex I respiratory capacity at 60R and both complex
      I and II function at 18hr (p<0.05). AVP was also associated with decreased
      reactive oxygen species at 60R (856+/-67 vs 622+/-48F RFU) and significantly
      decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9+/
      0.1 vs 1.7+/-0.1 fold change, p<0.01) and nitrosylation (0.9+/-0.1 vs 1.4+/-0.2
      fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic
      architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP
      levels decrease during severe hemorrhage and may contribute to the development of
      decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation
      improves blood pressure, preserves renal mitochondrial function, and mitigates
      acute kidney injury.

PMID- 29065124
TI  - Sustained virological response halts fibrosis progression: A long-term follow-up
      study of people with chronic hepatitis C infection.
AB  - BACKGROUND/AIMS: Long-term follow-up studies validating the clinical benefit of
      sustained virological response (SVR) in people with chronic hepatitis C (CHC)
      infection are lacking. Our aim was to identify rates and predictors of liver
      fibrosis progression in a large, well characterized cohort of CHC patients in
      whom paired liver fibrosis assessments were performed more than 10 years apart.
      METHODS: CHC patients who had undergone a baseline liver biopsy pre-2004 and a
      follow up liver fibrosis assessment more than 10 years later (biopsy or liver
      stiffness measurement (LSM) using transient elastography [FibroScan]) were
      identified. Subjects who had undergone a baseline liver biopsy but had no follow
      up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild
      moderate (METAVIR F0-2 / LSM result of <= 9.5 kPa) or advanced (METAVIR F3-4/ LSM
      >9.5 kPa). The primary objective was to assess the association between SVR and
      the rate of liver fibrosis progression over at least 10 years, defined as an
      increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to
      advanced fibrosis at follow-up liver fibrosis assessment. RESULTS: 131 subjects
      were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV.
      The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median
      estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis
      assessment was performed by LSM in 86% and liver biopsy in 14%. The median period
      between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had
      received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was
      a significant increase in the proportion of subjects with advanced liver
      fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced
      fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U
      (p = 0.343). However, advanced fibrosis became more common at F/U among subjects
      with persistent viremia: 10% at B/L vs 31% at F/U (p = 0.0001). SVR was
      independently associated with protection from liver fibrosis progression after
      adjustment for other variables including baseline ALT (p = 0.011), duration of
      HCV infection and mode of acquisition. CONCLUSION: HCV eradication is associated
      with lower rates of liver fibrosis progression. The data support early treatment
      to prevent long-term liver complications of HCV infection.

PMID- 29065125
TI  - The perceived feasibility of methods to reduce publication bias.
AB  - Publication bias is prevalent within the scientific literature. Whilst there are
      multiple ideas on how to reduce publication bias, only a minority of journals
      have made substantive changes to address the problem. We aimed to explore the
      perceived feasibility of strategies to reduce publication bias by gauging
      opinions of journal editors (n = 73) and other academics/researchers (n = 160)
      regarding nine methods of publishing and peer-reviewing research: mandatory
      publication, negative results journals/articles, open reviewing, peer-review
      training and accreditation, post-publication review, pre-study publication of
      methodology, published rejection lists, research registration, and two-stage
      review. Participants completed a questionnaire asking both quantitative (multiple
      choice or Likert scales) and qualitative (open-ended) questions regarding the
      barriers to implementing each suggestion, and their strengths and limitations.
      Participants were asked to rate the nine suggestions, then choose the method they
      felt was most effective. Mandatory publication was most popularly selected as the
      'most effective' method of reducing publication bias for editors (25%), and was
      the third most popular choice for academics/researchers (14%). The most common
      selection for academics/researchers was two-stage review (26%), but fewer editors
      prioritised this (11%). Negative results journals/articles were the second and
      third most common choices for academics/researchers (21%) and editors (16%),
      respectively. Editors more commonly chose research registration as 'most
      effective' (21%), which was favoured by only 6% of academics/researchers. Whilst
      mandatory publication was generally favoured by respondents, it is infeasible to
      trial at a journal level. Where suggestions have already been implemented (e.g.
      negative results journals/articles, trial registration), efforts should be made
      to objectively assess their efficacy. Two-stage review should be further trialled
      as its popularity amongst academics/researchers suggests it may be well received,
      though editors may be less receptive. Several underlying barriers to change also
      emerged, including scientific culture, impact factors, and researcher training;
      these should be further explored to reduce publication bias.

PMID- 29065127
TI  - Effectiveness of cervical screening after age 60 years according to screening
      history: Nationwide cohort study in Sweden.
AB  - BACKGROUND: The relatively high incidence of cervical cancer in women at older
      ages is a continuing concern in countries with long-established cervical
      screening. Controversy remains on when and how to cease screening. Existing
      population-based studies on the effectiveness of cervical screening at older ages
      have not considered women's screening history. We performed a nationwide cohort
      study to investigate the incidence of cervical cancer after age 60 years and its
      association with cervical screening at age 61-65, stratified by screening history
      at age 51-60. METHODS AND FINDINGS: Using the Total Population Register, we
      identified 569,132 women born between 1 January 1919 and 31 December 1945,
      resident in Sweden since age 51. Women's cytological screening records, cervical
      cancer occurrence, and FIGO stage (for those diagnosed with cancer) were
      retrieved from national registers and medical charts. We calculated the
      cumulative incidence of cervical cancer from age 61 to age 80 using a survival
      function considering competing risk, and estimated the hazard ratio (HR) of
      cervical cancer in relation to screening status at age 61-65 from Cox models,
      adjusted for birth cohort and level of education, conditioning on women's
      screening history in their 50s. In women unscreened in their 50s, the cumulative
      incidence up to age 80 was 5.0 per 1,000 women, and screening at age 61-65 was
      associated with a lower risk for cervical cancer (HR = 0.42, 95% CI 0.24-0.72),
      corresponding to a decrease of 3.3 cancer cases per 1,000 women. A higher
      cumulative incidence and similarly statistically significant risk decrease was
      seen for women with abnormal smears in their 50s. In women adequately or
      inadequately screened with only normal results between age 51 and age 60, the
      cumulative incidence of cervical cancer from age 61 to 80 was 1.6 and 2.5 per
      1,000 women, respectively, and further screening at age 61-65 was not associated
      with statistically significant decreases of cervical cancer risk up to age 80,
      but with fewer cancer cases of advanced stages at age 61-65. Adjustment for
      potential lifestyle confounders was limited. CONCLUSIONS: In this study, cervical
      screening with cytology at age 61-65 was associated with a statistically
      significant reduction of subsequent cervical cancer risk for women who were
      unscreened, or screened with abnormalities, in their 50s. In women screened with
      normal results in their 50s, the risk for future cancer was not sizeable, and the
      risk reduction associated with continued screening appeared limited. These
      findings should inform the current debate regarding age and criteria to
      discontinue cervical screening.

PMID- 29065128
TI  - A statistically rigorous sampling design to integrate avian monitoring and
      management within Bird Conservation Regions.
AB  - Monitoring is an essential component of wildlife management and conservation.
      However, the usefulness of monitoring data is often undermined by the lack of 1)
      coordination across organizations and regions, 2) meaningful management and
      conservation objectives, and 3) rigorous sampling designs. Although many
      improvements to avian monitoring have been discussed, the recommendations have
      been slow to emerge in large-scale programs. We introduce the Integrated
      Monitoring in Bird Conservation Regions (IMBCR) program designed to overcome the
      above limitations. Our objectives are to outline the development of a
      statistically defensible sampling design to increase the value of large-scale
      monitoring data and provide example applications to demonstrate the ability of
      the design to meet multiple conservation and management objectives. We outline
      the sampling process for the IMBCR program with a focus on the Badlands and
      Prairies Bird Conservation Region (BCR 17). We provide two examples for the
      Brewer's sparrow (Spizella breweri) in BCR 17 demonstrating the ability of the
      design to 1) determine hierarchical population responses to landscape change and
      2) estimate hierarchical habitat relationships to predict the response of the
      Brewer's sparrow to conservation efforts at multiple spatial scales. The
      collaboration across organizations and regions provided economy of scale by
      leveraging a common data platform over large spatial scales to promote the
      efficient use of monitoring resources. We designed the IMBCR program to address
      the information needs and core conservation and management objectives of the
      participating partner organizations. Although it has been argued that
      probabilistic sampling designs are not practical for large-scale monitoring, the
      IMBCR program provides a precedent for implementing a statistically defensible
      sampling design from local to bioregional scales. We demonstrate that integrating
      conservation and management objectives with rigorous statistical design and
      analyses ensures reliable knowledge about bird populations that is relevant and
      integral to bird conservation at multiple scales.

PMID- 29065126
TI  - Giardiasis as a neglected disease in Brazil: Systematic review of 20 years of
      publications.
AB  - INTRODUCTION: Giardiasis is an intestinal infection that affects more than two
      hundred million people annually worldwide; it is caused by the flagellated
      protozoan Giardia duodenalis. In tropical countries and in low or middle-income
      settings, like Brazil, its prevalence can be high. There is currently no
      systematic review on the presence of G. duodenalis in patients, animals or water
      sources in Brazil. METHODS: This systematic review was performed according to
      recommendations established by Preferred Reporting Items for Systematic Reviews
      and Meta-Analysis (PRISMA). As databases for our searches, we have used PubMed,
      Embase, Scopus and the Brazilian database SciELO using the keywords "Giardia*"
      and "Brazil". RESULTS: This systematic review identified research studies related
      to G. duodenalis in water, giardiasis in animals, prevalence of giardiasis across
      Brazilian regions, genotyping of strains isolated in humans, and giardiasis in
      indigenous populations. We also propose a network of G. duodenalis transmission
      in Brazil based on genotypes analyses. CONCLUSION: This is the first time within
      the last twenty years that a review is being published on the occurrence of G.
      duodenalis in Brazil, addressing relevant issues such as prevalence, molecular
      epidemiology and analytical methods for parasite detection.

PMID- 29065129
TI  - An equity analysis of health examination service utilization by women from
      underdeveloped areas in western China.
AB  - OBJECTIVE: This study sought to examine the sources of inequity in health
      examination service utilization by women from underdeveloped areas in western
      China. METHODS: Based on data from the 5th National Health Service Survey in
      Shaanxi province, women's utilization of health examination services was examined
      according to gynecological, cervical smear, and breast examination rates. The
      equity of health examination service utilization by 15- to 64-year-old women and
      the factors contributing to inequity were determined using the health
      concentration index, decomposition of the concentration index, and the horizontal
      inequity index. RESULTS: The examination rates for gynecological, cervical smear,
      and breast exams for 15- to 64-year-old women in Shaanxi province were 40.61%,
      27.08%, and 24.59%, respectively. The horizontal inequity indices of
      gynecological, cervical smear, and breast examination rates were 0.0480, 0.0423,
      and 0.0764, respectively, and each examination rate was higher for wealthy
      individuals. The contribution rates of economic status to the inequalities in
      gynecological, cervical smear, and breast examination rates were 65.80%, 74.31%,
      and 56.49%, respectively. The contribution rates of educational status to the
      inequalities in gynecological, cervical smear, and breast examination rates were
      21.01%, 14.83% and 30.00%, respectively. The contribution rates of age to the
      inequalities in gynecological, cervical smear, and breast examination rates were
      25.77%, 26.55%, and 18.40%, respectively. CONCLUSIONS: Women's health examination
      rates differed between populations with different socio-demographic
      characteristics. There is pro-wealth inequality in each examination rate. This
      study found that financial status, age, and education level were the main reasons
      for the unequal utilization of health examination services.

PMID- 29065130
TI  - Metabolic syndrome and Chronic Obstructive Pulmonary Disease (COPD): The
      interplay among smoking, insulin resistance and vitamin D.
AB  - BACKGROUND: A close relationship between Metabolic Syndrome (MetS) and Chronic
      Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of
      this link remains unclear. Current epidemiological data refer exclusively to the
      MetS prevalence among patients with COPD and data about the prevalence of COPD in
      MetS patients are still unavailable. AIM OF THE STUDY: To analyse and compare
      risk factors, clinical and metabolic characteristics, as well as the main
      respiratory function parameters, among patients affected by MetS, COPD or both
      diseases. PATIENTS: We recruited 59 outpatients with MetS and 76 outpatients with
      COPD. After medical history collection, physical examination, blood sampling for
      routine analysis, spirometric evaluation, they were subdivided into MetS (n =
      46), MetS+COPD (n = 60), COPD (n = 29). RESULTS: A MetS diagnosis was assigned to
      62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology
      Department, while the COPD prevalence in MetS patients enrolled in the Internal
      Medicine Metabolic Disorders Outpatients Clinic was 22%. More than 60% of
      subjects enrolled in each Department were unaware that they suffered from an
      additional disease. MetS+COPD patients exhibited significantly higher C-peptide
      levels. We also found a positive relation between C-peptide and pack-years in all
      subjects and a negative correlation between C-peptide and vitamin D only in
      current smokers. Finally, a negative association emerged between smoking and
      vitamin D. CONCLUSIONS: We have estimated, for the first time, the COPD
      prevalence in MetS and suggest a potential role of smoking in inducing insulin
      resistance. Moreover, a direct effect of smoking on vitamin D levels is proposed
      as a novel mechanism, which may account for both insulin resistance and COPD
      development.

PMID- 29065131
TI  - Kinetic characterization of Vibrio cholerae ApbE: Substrate specificity and
      regulatory mechanisms.
AB  - ApbE is a member of a novel family of flavin transferases that incorporates
      flavin mononucleotide (FMN) to subunits of diverse respiratory complexes, which
      fulfill important homeostatic functions. In this work a detailed characterization
      of Vibrio cholerae ApbE physiologic activity, substrate specificity and pH
      dependency was carried out. The data obtained show novel characteristics of the
      regulation and function of this family. For instance, our experiments indicate
      that divalent cations are essential for ApbE function, and that the selectivity
      depends largely on size and the coordination sphere of the cation. Our data also
      show that ApbE regulation by pH, ADP and potassium is an important mechanism that
      enhances the adaptation, survival and colonization of V. cholerae in the small
      intestine. Moreover, studies of the pH-dependency of the activity show that the
      reaction is favored under alkaline conditions, with a pKa of 8.4. These studies,
      together with sequence and structure analysis allowed us to identify His257,
      which is absolutely conserved in the family, as a candidate for the residue whose
      deprotonation controls the activity. Remarkably, the mutant H257G abolished the
      flavin transfer activity, strongly indicating that this residue plays an
      important role in the catalytic mechanism of ApbE.

PMID- 29065133
TI  - Trajectory modeling of gestational weight: A functional principal component
      analysis approach.
AB  - Suboptimal gestational weight gain (GWG), which is linked to increased risk of
      adverse outcomes for a pregnant woman and her infant, is prevalent. In the study
      of a large cohort of Canadian pregnant women, our goals are to estimate the
      individual weight growth trajectory using sparsely collected bodyweight data, and
      to identify the factors affecting the weight change during pregnancy, such as
      prepregnancy body mass index (BMI), dietary intakes and physical activity. The
      first goal was achieved through functional principal component analysis (FPCA) by
      conditional expectation. For the second goal, we used linear regression with the
      total weight gain as the response variable. The trajectory modeling through FPCA
      had a significantly smaller root mean square error (RMSE) and improved
      adaptability than the classic nonlinear mixed-effect models, demonstrating a
      novel tool that can be used to facilitate real time monitoring and interventions
      of GWG. Our regression analysis showed that prepregnancy BMI had a high
      predictive value for the weight changes during pregnancy, which agrees with the
      published weight gain guideline.

PMID- 29065132
TI  - Correlates of condomless anal sex among men who have sex with men (MSM) in
      Tijuana, Mexico: The role of public sex venues.
AB  - Condomless anal sex between male partners is the primary risk factor for HIV
      transmission among men who have sex with men (MSM). Correlates of condomless anal
      sex have been well-studied in developed countries, but they have received less
      attention in lower-to-middle income countries (LMIC), where MSM are often subject
      to stigma, discrimination, intolerance, and even the criminalization of same sex
      behavior. In Mexico, a LMIC where traditional views on homosexuality are common,
      HIV prevalence among MSM is high (16.9%), yet little research has been conducted
      on the correlates of condomless anal sex in this high-risk population. The
      present study examined correlates of condomless anal sex among 201 MSM recruited
      in Tijuana, Mexico, with a focus on the role of public sex venues in relation to
      sexual risk behavior. Eligibility requirements were: biologically male, 18 years
      of age or older, resident of Tijuana, and self-reported anal or oral sex with a
      male partner in the past year. Participants completed an interviewer
      administered, demographic and psychosocial survey, and were tested for HIV and
      syphilis. A hierarchical multiple linear regression model was tested to identify
      correlates of condomless anal sex. Thirty-eight percent of participants (N = 76)
      reported condomless anal sex with a male partner in the past 2 months. Higher
      levels of condomless anal sex were associated with higher levels of depressive
      symptoms, greater sexual compulsivity, and more frequent seeking out of sex
      partners in a public venue in the past 2 months. In view of these findings, we
      recommend the development of multi-level, "combination" interventions, which in
      the Mexican context should include enhanced condom promotion and distribution,
      improved availability and access to mental health treatment and counseling
      services, and expanded HIV/STI testing in public venues.

PMID- 29065134
TI  - Functional polymorphism of the renalase gene is associated with cardiac
      hypertrophy in female patients with aortic stenosis.
AB  - Renalase decreases circulating catecholamines concentration and is important in
      maintaining primary cellular metabolism. Renalase acts through the plasma
      membrane calcium ATPase 4b in the heart, which affects pressure overload but not
      exercise induced heart hypertrophy. The aim of this study was to test the
      association between a functional polymorphism Glu37Asp (rs2296545) of the
      renalase gene and left ventricular hypertrophy in a large cohort of patients with
      aortic stenosis. The study group consisted of 657 patients with aortic stenosis
      referred for aortic valve replacement. Preoperative echocardiographic assessment
      was performed to obtain cardiac phenotypes. Generalized-linear models were
      implemented to analyze data using crude or full model adjusted for selected
      clinical factors. In females, the Asp37 variant of the Glu37Asp polymorphism was
      associated with higher left ventricular mass (p = 0.0021 and p = 0.055 crude and
      full model respectively), intraventricular septal thickness (p = 0.0003 and p =
      0.0143) and posterior wall thickness (p = 0.0005 and p = 0.0219) all indexed to
      body surface area, as well as relative wall thickness (p = 0.001 and p = 0.0097).
      No significant associations were found among the male patients. In conclusion, we
      have found the association of the renalase Glu37Asp polymorphism with left
      ventricle hypertrophy in large group of females with aortic stenosis. The
      Glu37Asp polymorphism causes not only amino-acid substitution in FAD binding
      domain but may also change binding affinity of the hypoxia- and hypertrophy
      related transcription factors and influence renalase gene expression. Our data
      suggest that renalase might play a role in hypertrophic response to pressure
      overload, but the exact mechanism requires further investigation.

PMID- 29065135
TI  - The preclinical analysis of TW-37 as a potential anti-colorectal cancer cell
      agent.
AB  - TW-37 is a novel, potent and non-peptide Bcl-2 small-molecule inhibitor. Its
      activity in colorectal cancer (CRC) cells is studied. In both HCT-116 cells and
      primary human colon cancer cells, treatment with TW-37 at only nM concentration
      efficiently inhibited cell survival and proliferation. TW-37 also induced caspase
      3/9 and apoptosis activation in CRC cells. Feedback autophagy activation was
      observed in TW-37-treated CRC cells. Reversely pharmacological autophagy
      inhibition or Beclin-1 knockdown by targeted-shRNA potentiated TW-37-induced
      apoptosis and killing of CRC cells. In vivo, intravenous injection of TW-37
      inhibited HCT-116 tumor growth in mice. TW-37's anti-tumor activity was further
      potentiated against Beclin-1-silenced HCT-116 tumors. Together, targeting Bcl-2
      family protein by TW-37 efficiently inhibits CRC cell growth in vitro and in
      vivo. Inhibition of feedback autophagy activation could further sensitize TW-37.

PMID- 29065136
TI  - Collective motion of predictive swarms.
AB  - Theoretical models of populations and swarms typically start with the assumption
      that the motion of agents is governed by the local stimuli. However, an
      intelligent agent, with some understanding of the laws that govern its habitat,
      can anticipate the future, and make predictions to gather resources more
      efficiently. Here we study a specific model of this kind, where agents aim to
      maximize their consumption of a diffusing resource, by attempting to predict the
      future of a resource field and the actions of other agents. Once the agents make
      a prediction, they are attracted to move towards regions that have, and will
      have, denser resources. We find that the further the agents attempt to see into
      the future, the more their attempts at prediction fail, and the less resources
      they consume. We also study the case where predictive agents compete against non
      predictive agents and find the predictors perform better than the non-predictors
      only when their relative numbers are very small. We conclude that predictivity
      pays off either when the predictors do not see too far into the future or the
      number of predictors is small.

PMID- 29065137
TI  - Differences in the population structure of Neisseria meningitidis in two
      Australian states: Victoria and Western Australia.
AB  - Neisseria meningitidis is the causative agent of invasive meningococcal disease
      (IMD). A recombinant vaccine called Bexsero(r) incorporates four subcapsular
      antigens (fHbp, NHBA, NadA and PorA) which are used to assign a Bexsero(r)
      antigen sequence type (BAST) to each meningococcal strain. The vaccine elicits an
      immune response against combinations of variants of these antigens which have
      been grouped into specific BAST profiles that have been shown to have different
      distributions within geographical locations thus potentially affecting the
      efficacy of the vaccine. In this study, invasive meningococcal disease isolates
      from the western seaboard of Australia (Western Australia; WA) were compared to
      those from the south-eastern seaboard (Victoria; VIC) from 2008 to 2012. Whole
      genome sequencing (WGS) of 131 meningococci from VIC and 70 meningococci from WA
      were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both
      jurisdictions and a total of 10 MLST clonal complexes (cc) were shared by both
      states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst
      isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented
      one-third of the meningococcal population in each state but the predominant ST
      was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles
      identified in this collection, only 9 BASTs were simultaneously observed in both
      states. A significantly larger proportion of isolates in VIC harboured alleles
      for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by
      the Bexsero(r) vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI:
      41.1-53.1%]) was significantly lower than that in VIC (66.4% [95% CI: 62.3
      70.5%]). In conclusion, the antigenic structure of meningococci causing invasive
      disease in two geographically distinct states of Australia differed significantly
      during the study period which may affect vaccine effectiveness and highlights the
      need for representative surveillance when predicting potential impact of
      meningococcal B vaccines.

PMID- 29065138
TI  - In situ fibrillizing amyloid-beta 1-42 induces neurite degeneration and apoptosis
      of differentiated SH-SY5Y cells.
AB  - The progression of Alzheimer's disease is causatively linked to the accumulation
      of amyloid-beta aggregates in the brain, however, it is not clear how the amyloid
      aggregates initiate the death of neuronal cells. The in vitro toxic effects of
      amyloid peptides are most commonly examined using the human neuroblastoma derived
      SH-SY5Y cell line and here we show that differentiated neuron-like SH-SY5Y cells
      are more sensitive to amyloid peptides than non-differentiated cells, because the
      latter lack long neurites. Exogenous soluble amyloid-beta 1-42 covered cell
      bodies and whole neurites in differentiated cells with dense fibrils, causing
      neurite beading and fragmentation, whereas preformed amyloid-beta 1-42 fibrils
      had no toxic effects. Importantly, spontaneously fibrillizing amyloid-beta 1-42
      peptide exhibited substantially higher cellular toxicity than amyloid-beta 1-40,
      which did not form fibrils under the experimental conditions. These results
      support the hypothesis that peptide toxicity is related to the active
      fibrillization process in the incubation mixture.

PMID- 29065139
TI  - CLEC9A modulates macrophage-mediated neutrophil recruitment in response to heat
      killed Mycobacterium tuberculosis H37Ra.
AB  - Tuberculosis is a fatal human infectious disease caused by Mycobacterium
      tuberculosis (M. tuberculosis) that is prevalent worldwide. Mycobacteria differ
      from other bacteria in that they have a cell wall composed of specific surface
      glycans that are the major determinant of these organisms' pathogenicity. The
      interaction of M. tuberculosis with pattern recognition receptors (PRRs), in
      particular C-type lectin receptors (CLRs), on the surface of macrophages plays a
      central role in initiating innate and adaptive immunity, but the picture as a
      whole remains a puzzle. Defining novel mechanisms by which host receptors
      interact with pathogens in order to modulate a specific immune response is an
      area of intense research. In this study, based on an in vitro lectin binding
      assay, CLEC9A (DNGR-1) is identified as a novel CLR that binds with mycobacteria.
      Our results with CLEC9A-knocked down cells and a CLEC9A-Fc fusion protein as
      blocking agents show that CLEC9A is involved in the activation of SYK and MAPK
      signaling in response to heat-killed M. tuberculosis H37Ra treatment, and it then
      promotes the production of CXCL8 and IL-1beta in macrophages. The CXCL8 and IL
      1beta secreted by the activated macrophages are critical to neutrophil
      recruitment and activation. In a in vivo mouse model, when the interaction
      between CLEC9A and H37Ra is interfered with by treatment with CLEC9A-Fc fusion
      protein, this reduces lung inflammation and cell infiltration. These findings
      demonstrate that CLEC9A is a specialized receptor that modulates the innate
      immune response when there is a mycobacterial infection.

PMID- 29065140
TI  - Novel insights into the pathways regulating the canine hair cycle and their
      deregulation in alopecia X.
AB  - Alopecia X is a hair cycle arrest disorder in Pomeranians. Histologically,
      kenogen and telogen hair follicles predominate, whereas anagen follicles are
      sparse. The induction of anagen relies on the activation of hair follicle stem
      cells and their subsequent proliferation and differentiation. Stem cell function
      depends on finely tuned interactions of signaling molecules and transcription
      factors, which are not well defined in dogs. We performed transcriptome profiling
      on skin biopsies to analyze altered molecular pathways in alopecia X. Biopsies
      from five affected and four non-affected Pomeranians were investigated.
      Differential gene expression revealed a downregulation of key regulator genes of
      the Wnt (CTNNB1, LEF1, TCF3, WNT10B) and Shh (SHH, GLI1, SMO, PTCH2) pathways. In
      mice it has been shown that Wnt and Shh signaling results in stem cell activation
      and differentiation Thus our findings are in line with the lack of anagen hair
      follicles in dogs with Alopecia X. We also observed a significant downregulation
      of the stem cell markers SOX9, LHX2, LGR5, TCF7L1 and GLI1 whereas NFATc1, a
      quiescence marker, was upregulated in alopecia X. Moreover, genes coding for
      enzymes directly involved in the sex hormone metabolism (CYP1A1, CYP1B1,
      HSD17B14) were differentially regulated in alopecia X. These findings are in
      agreement with the so far proposed but not yet proven deregulation of the sex
      hormone metabolism in this disease.

PMID- 29065141
TI  - High-performance wireless powering for peripheral nerve neuromodulation systems.
AB  - Neuromodulation of peripheral nerves with bioelectronic devices is a promising
      approach for treating a wide range of disorders. Wireless powering could enable
      long-term operation of these devices, but achieving high performance for
      miniaturized and deeply placed devices remains a technological challenge. We
      report the miniaturized integration of a wireless powering system in soft
      neuromodulation device (15 mm length, 2.7 mm diameter) and demonstrate high
      performance (about 10%) during in vivo wireless stimulation of the vagus nerve in
      a porcine animal model. The increased performance is enabled by the generation of
      a focused and circularly polarized field that enhances efficiency and provides
      immunity to polarization misalignment. These performance characteristics
      establish the clinical potential of wireless powering for emerging therapies
      based on neuromodulation.

PMID- 29065143
TI  - A roaring trade? The legal trade in Panthera leo bones from Africa to East
      Southeast Asia.
AB  - The African lion is the only big cat listed on CITES Appendix II, and the only
      one for which international commercial trade is legal under CITES. The trade in
      lion body parts, and especially the contentious trade in bones from South Africa
      to Asia, has raised concerns spanning continents and cultures. Debates were
      amplified at the 2016 CITES Conference of the Parties (CoP17) when a proposal to
      up-list lions to Appendix I was not supported and a compromise to keep them on
      Appendix II, with a bone trade quota for South Africa, was reached instead. CoP17
      underscored a need for further information on the lion bone trade and the
      consequences for lions across the continent. Legal international trade in bones
      to Asia, allegedly to supply the substitute 'tiger bone' market, began in South
      Africa in February 2008 when the first CITES permits were issued. It was
      initially unclear the degree to which bones were sourced from captive-origin
      lions, and whether trade was a threat to wild lion populations. Our original
      assessment of the legal CITES-permitted lion bone trade from South Africa to East
      Southeast Asia was for the period 2008-2011 (published 2015). In this paper, we
      consolidate new information that has become available for 2012-2016, including
      CITES reports from other African countries, and data on actual exports for three
      years to 2016 supplied by a freight forwarding company. Thus, we update the
      figures on the legal trade in lion bones from Africa to East-Southeast Asia in
      the period 2008-2016. We also contextualise the basis for global concerns by
      reviewing the history of the trade and its relation to tigers, poaching and
      wildlife trafficking. CITES permits issued to export bones escalated from +/-314y
      1 skeletons from 2008-2011, to +/-1312y-1 skeletons from 2013-2015. South Africa
      was the only legal exporter of bones to Asia until 2013 when Namibia issued
      permits to export skeletons to Vietnam. While CITES permits to export +/-5363
      skeletons from Africa to Asia from 2008-2015 were issued (99.1% from South
      Africa; 0.7% from Namibia) (51% for Laos), actual exports were less than stated
      on the permits. However, information on actual exports from 2014-2016 indicated
      that >3400 skeletons were exported in that period. In total, >6000 skeletons
      weighing no less than 70 tonnes have been shipped to East-Southeast Asia since
      2008. Since few wild lions are hunted and poached within South African protected
      areas, skeletons for the legal trade appear to be derived from captive bred
      lions. However, confirmation of a 116kg shipment from Uganda to Laos, and reports
      of lion poaching in neighbouring countries, indicate that urgent proactive
      monitoring and evaluation of the legal and illegal trade is necessary in African
      lion range states where vulnerable wild lion populations are likely to be
      adversely affected.

PMID- 29065142
TI  - Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following
      a late MVA-B boost 4 years after the last immunization.
AB  - BACKGROUND: We have previously shown that an HIV vaccine regimen including three
      doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from
      clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and
      antibody responses in 75% and 95% of HIV-negative volunteers (n = 24),
      respectively (RISVAC02 study). Here, we describe the long-term durability of
      vaccine-induced responses and the safety and immunogenicity of an additional MVA
      B boost. METHODS: 13 volunteers from the RISVAC02 trial were recruited to receive
      a fourth dose of MVA-B 4 years after the last immunization. End-points were
      safety, cellular and humoral immune responses to HIV-1 and vector antigens
      assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed
      before and 2, 4 and 12 weeks after receiving the boost. RESULTS: Volunteers
      reported 64 adverse events (AEs), although none was a vaccine-related serious AE.
      After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low
      HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in
      IFN-gamma T-cell responses, mainly directed against Env, was detected by ELISPOT
      in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers
      showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+
      T cell-responses were similarly distributed against Env, Gag and GPN. In terms of
      antibody responses, 23.1% of the vaccinees had detectable Env-specific binding
      antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5.
      The late MVA-B boost significantly improved both the response rate (92.3%) and
      the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460).
      HIV-1 neutralizing antibodies were also enhanced and detected in 77% of
      volunteers. Moreover, MVA vector-specific T cell and antibody responses were
      boosted in 80% and 100% of volunteers respectively. CONCLUSIONS: One boost of MVA
      B four years after receiving 3 doses of the same vaccine was safe, induced
      moderate increases in HIV-specific T cell responses in 38% of volunteers but
      significantly boosted the binding and neutralizing antibody responses to HIV-1
      and to the MVA vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT01923610.

PMID- 29065145
TI  - A Markovian model of evolving world input-output network.
AB  - The initial theoretical connections between Leontief input-output models and
      Markov chains were established back in 1950s. However, considering the wide
      variety of mathematical properties of Markov chains, so far there has not been a
      full investigation of evolving world economic networks with Markov chain
      formalism. In this work, using the recently available world input-output
      database, we investigated the evolution of the world economic network from 1995
      to 2011 through analysis of a time series of finite Markov chains. We assessed
      different aspects of this evolving system via different known properties of the
      Markov chains such as mixing time, Kemeny constant, steady state probabilities
      and perturbation analysis of the transition matrices. First, we showed how the
      time series of mixing times and Kemeny constants could be used as an aggregate
      index of globalization. Next, we focused on the steady state probabilities as a
      measure of structural power of the economies that are comparable to GDP shares of
      economies as the traditional index of economies welfare. Further, we introduced
      two measures of systemic risk, called systemic influence and systemic fragility,
      where the former is the ratio of number of influenced nodes to the total number
      of nodes, caused by a shock in the activity of a node, and the latter is based on
      the number of times a specific economic node is affected by a shock in the
      activity of any of the other nodes. Finally, focusing on Kemeny constant as a
      global indicator of monetary flow across the network, we showed that there is a
      paradoxical effect of a change in activity levels of economic nodes on the
      overall flow of the world economic network. While the economic slowdown of the
      majority of nodes with high structural power results to a slower average monetary
      flow over the network, there are some nodes, where their slowdowns improve the
      overall quality of the network in terms of connectivity and the average flow of
      the money.

PMID- 29065144
TI  - Substantial vertebral body osteophytes protect against severe vertebral fractures
      in compression.
AB  - Recent findings suggest that vertebral osteophytes increase the resistance of the
      spine to compression. However, the role of vertebral osteophytes on the
      biomechanical response of the spine under fast dynamic compression, up to
      failure, is unclear. Seventeen human spine specimens composed of three vertebrae
      (from T5-T7 to T11-L1) and their surrounding soft tissues were harvested from
      nine cadavers, aged 77 to 92 years. Specimens were imaged using quantitative
      computer tomography (QCT) for medical observation, classification of the
      intervertebral disc degeneration (Thomson grade) and measurement of the vertebral
      trabecular density (VTD), height and cross-sectional area. Specimens were divided
      into two groups (with (n = 9) or without (n = 8) substantial vertebral body
      osteophytes) and compressed axially at a dynamic displacement rate of 1 m/s, up
      to failure. Normalized force-displacement curves, videos and QCT images allowed
      characterizing failure parameters (force, displacement and energy at failure) and
      fracture patterns. Results were analyzed using chi-squared tests for sampling
      distributions and linear regression for correlations between VTD and failure
      parameters. Specimens with substantial vertebral body osteophytes present higher
      stiffness (2.7 times on average) and force at failure (1.8 times on average) than
      other segments. The presence of osteophytes significantly influences the
      location, pattern and type of fracture. VTD was a good predictor of the dynamic
      force and energy at failure for specimens without substantial osteophytes. This
      study also showed that vertebral body osteophytes provide a protective mechanism
      to the underlying vertebra against severe compression fractures.

PMID- 29065146
TI  - Right dorsal colon ultrasonography in normal adult ponies and miniature horses.
AB  - The aim of this study was to determine the normal location, wall thickness and
      motility of the right dorsal colon in adult ponies and miniature horses. The
      abdominal ultrasonography examination was performed in a study group consisting
      of 23 ponies and miniature horses and in a control group comprising ten
      Thoroughbred horses. The procedure was performed in unsedated standing animals.
      The location and the thickness of the right dorsal colonic wall was examined on
      the right side of the abdomen between the 10th and the 14th intercostal space.
      The contractility was recorded in the 12th intercostal space. A comparative
      analysis between the study group and control group was carried out using the
      Student's t-test. Pearson's linear correlation coefficient was used to calculate
      the correlation between the thickness of the colonic wall as well as the number
      of peristaltic movements and age, wither height and body mass of the animals. The
      right dorsal colon was identified in all the horses in the 12th intercostal
      space. In all the intercostal spaces the mean +/- standard deviation (SD) wall
      thickness of the right dorsal colon was 0.27 +/- 0.03 cm in the horses from the
      study group and 0.37 +/- 0.03 cm in the control horses. The mean number of
      peristaltic contractions was 4.05 +/- 1.07 per minute in the animals from the
      study group and 1.7 +/- 0.46 contractions per minute in the control group. The
      values of the ultrasonographic wall thickness and peristaltic motility in small
      breed horses in the present study were different from the values obtained for
      large breed horses. The study also found that the right dorsal colon in small
      breed horses is physiologically located in the 12th intercostal space. This
      suggests that different reference values should be used in small horse breeds
      when performing an ultrasound examination.

PMID- 29065147
TI  - Developing citizen report cards for primary health care in low and middle-income
      countries: Results from cognitive interviews in rural Tajikistan.
AB  - Citizen report cards on health care providers have been identified as a potential
      means to increase citizen engagement, provider accountability and health systems
      performance. Research in high-income settings indicates that the wording,
      presentation and display of performance information are critical to achieve these
      goals. However, there are limited insights on developing effective report card
      designs for middle- and low-income settings. We conducted cognitive interviews to
      assess consumers' understanding, interpretation of and preferences for displaying
      information for a health care report card in rural Tajikistan. We recruited a
      convenience sample of 40 citizens (20 women and 20 men aged 18-45) from rural
      areas of two provinces of Tajikistan (Soghd and Khatlon oblasts). The interview
      protocol was adapted from the model of cognitive interviews used in social
      science research to improve survey questionnaires. We used multivariate
      regression to assess understanding and interpretation of the report card; chi2
      tests to assess differences in preferences for displaying information; and tests
      of proportions to assess the preferred comparison group. Respondents understood
      the main idea of the report card and are not confused by the indicators or
      display. However, many respondents had difficulties making comparisons, and when
      asked to identify worst-performing services. Respondents preferred detailed
      rankings using school grades, comparisons of their local clinic with the regional
      or national average performance, and the use of color in the report card. We
      found some heterogeneity across the two provinces. Overall, our findings are
      promising regarding the citizens' comprehension of health care report cards in
      rural Tajikistan, while underscoring the challenges of effectively providing
      health care performance information to communities. Cognitive interviews and
      iterative testing can support an effective implementation of reporting
      initiatives.

PMID- 29065148
TI  - Imagining the "open" university: Sharing scholarship to improve research and
      education.
AB  - Open scholarship, such as the sharing of articles, code, data, and educational
      resources, has the potential to improve university research and education as well
      as increase the impact universities can have beyond their own walls. To support
      this perspective, I present evidence from case studies, published literature, and
      personal experiences as a practicing open scholar. I describe some of the
      challenges inherent to practicing open scholarship and some of the tensions
      created by incompatibilities between institutional policies and personal
      practice. To address this, I propose several concrete actions universities could
      take to support open scholarship and outline ways in which such initiatives could
      benefit the public as well as institutions. Importantly, I do not think most of
      these actions would require new funding but rather a redistribution of existing
      funds and a rewriting of internal policies to better align with university
      missions of knowledge dissemination and societal impact.

PMID- 29065149
TI  - Outcomes of an HIV cohort after a decade of comprehensive care at Newlands Clinic
      in Harare, Zimbabwe: TENART cohort.
AB  - BACKGROUND: Data on long-term outcomes of patients receiving antiretroviral
      therapy (ART) in sub-Saharan Africa are few. We describe outcomes of patients
      commenced on ART at Newlands Clinic between 2004 and 2006 after >=10 years of
      comprehensive care including, psychosocial, adherence and food support. METHODS:
      In this retrospective cohort study, patient data from an electronic medical
      record collected during routine care were analysed. We describe baseline
      characteristics, virological and clinical outcomes, attrition rates, and
      treatment adverse effects until November 2016. We defined virological suppression
      as viral load <50 copies/ml and virological failure as >1000 copies/ml after >=6
      months of ART. RESULTS: We analysed data for 605 patients (67% female) who
      commenced ART, and were followed-up for 5819 person-years (median: 10.7 years,
      IQR: 10.1-11.4). Median age at ART initiation was 34 years (IQR: 17-42). Pre-ART,
      129 (21.3%) patients had history of pulmonary tuberculosis (PTB). In care, 66
      (11%) developed PTB, and 24 (4%) developed extrapulmonary tuberculosis. 385
      (63.6%) patients experienced >=1 adverse event, the most frequent being stavudine
      induced peripheral neuropathy (n = 252, 41.7%). At database closure on 14
      November 2016, 474 (78.3%) patients were still in care, 428 (90.3%) being
      virologically suppressed, and 21 (4.4%) failing. While 483 (79.8%) remained on
      first line, 122 (20.2%) were switched to second line ART. Fifty-nine patients
      (9.8%) were transferred to other ART facilities, 45 (7.4%) were lost to follow
      up, 25 (4.1%) died, and two stopped ART. CONCLUSION: Comprehensive HIV care can
      result in low mortality, high retention in care and virologic suppression rates
      in resource limited settings.

PMID- 29065150
TI  - Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery
      from injury.
AB  - Genetic disruption of the dystrophin complex produces muscular dystrophy
      characterized by a fragile muscle plasma membrane leading to excessive muscle
      degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the
      transforming growth factor beta (TGFbeta) pathway, osteopontin encoded by the
      SPP1 gene and latent TGFbeta binding protein 4 (LTBP4). We now evaluated the
      functional effect of these modifiers in the context of muscle injury and repair
      to elucidate their mechanisms of action. We found that excess osteopontin
      exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin
      reduced injury extent both in isolated myofibers and in muscle in vivo. We found
      that ablation of osteopontin was associated with reduced expression of TGFbeta
      and TGFbeta-associated pathways. We identified that increased TGFbeta resulted in
      reduced expression of Anxa1 and Anxa6, genes encoding key components of the
      muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic
      muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in
      concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide
      a model in which a feed forward loop of TGFbeta and osteopontin directly impacts
      the capacity of muscle to recover from injury, and identifies an intersection of
      genetic modifiers on muscular dystrophy.

PMID- 29065152
TI  - A deep transcriptomic resource for the copepod crustacean Labidocera madurae: A
      potential indicator species for assessing near shore ecosystem health.
AB  - Coral reef ecosystems of many sub-tropical and tropical marine coastal
      environments have suffered significant degradation from anthropogenic sources.
      Research to inform management strategies that mitigate stressors and promote a
      healthy ecosystem has focused on the ecology and physiology of coral reefs and
      associated organisms. Few studies focus on the surrounding pelagic communities,
      which are equally important to ecosystem function. Zooplankton, often dominated
      by small crustaceans such as copepods, is an important food source for
      invertebrates and fishes, especially larval fishes. The reef-associated
      zooplankton includes a sub-neustonic copepod family that could serve as an
      indicator species for the community. Here, we describe the generation of a de
      novo transcriptome for one such copepod, Labidocera madurae, a pontellid from an
      intensively-studied coral reef ecosystem, Kane'ohe Bay, Oahu, Hawai'i. The
      transcriptome was assembled using high-throughput sequence data obtained from
      whole organisms. It comprised 211,002 unique transcripts, including 72,391 with
      coding regions. It was assessed for quality and completeness using multiple
      workflows. Bench-marking-universal-single-copy-orthologs (BUSCO) analysis
      identified transcripts for 88% of expected eukaryotic core proteins. Targeted
      gene-discovery analyses included searches for transcripts coding full-length
      "giant" proteins (>4,000 amino acids), proteins and splice variants of voltage
      gated sodium channels, and proteins involved in the circadian signaling pathway.
      Four different reference transcriptomes were generated and compared for the
      detection of differential gene expression between copepodites and adult females;
      6,229 genes were consistently identified as differentially expressed between the
      two regardless of reference. Automated bioinformatics analyses and targeted
      manual gene curation suggest that the de novo assembled L. madurae transcriptome
      is of high quality and completeness. This transcriptome provides a new resource
      for assessing the global physiological status of a planktonic species inhabiting
      a coral reef ecosystem that is subjected to multiple anthropogenic stressors. The
      workflows provide a template for generating and assessing transcriptomes in other
      non-model species.

PMID- 29065153
TI  - Prognostic implication of EGFR gene mutations and histological classification in
      patients with resected stage I lung adenocarcinoma.
AB  - INTRODUCTION: The prognostic value of epidermal growth factor receptor (EGFR)
      mutations and the correlation between EGFR mutations and the new International
      Association for the Study of Lung Cancer/American Thoracic Society/European
      Respiratory Society (IASLC/ATS/ERS) histological classification remain
      controversial. The current study aimed to investigate the pure prognostic role of
      EGFR mutations in treatment-naive patients with resected stage I lung
      adenocarcinoma. METHODS: We retrospectively reviewed 373 patients with stage I
      pulmonary non-small-cell lung cancer who underwent complete surgical resection
      between January 2010 and May 2014. The tumors were classified according to
      IASLC/ATS/ERS criteria. EGFR mutation status was determined by established
      methods. RESULTS: A total of 120 patients were included for analysis; 87 had
      tumors with EGFR mutations and 33 had wild-type tumors. More low- and
      intermediate-grade tumors had EGFR mutations, and nearly half of the high-grade
      tumors were wild-type (75.7% versus 46.2%, p = 0.041). Patients with low-grade
      tumors had significantly greater median disease-free survival (DFS) (76.8 versus
      13 months, p < 0.0001) and better overall survival (OS) (median OS not reached, p
      = 0.0003) than those with intermediate- and high-grade tumors. Tumor recurrence
      was 41.4% and 30.3% in mutant and wild-type patients. The 5-years survival rate
      was 54% and 71.2%. Multivariate analysis revealed that the new histological
      classification and the pathologic stage were independent predictors of both DFS
      and OS. EGFR mutation status had no prognostic implications. CONCLUSION: Low
      grade tumors according to IASLC/ATS/ERS histological classification and the
      pathologic stage IA tumors of resected stage I lung adenocarcinomas independently
      predict better DFS and OS. EGFR mutations were frequently seen in histologically
      low- and intermediate-grade tumors but not a prognostic factor.

PMID- 29065154
TI  - Scaffolding the cup-shaped double membrane in autophagy.
AB  - Autophagy is a physiological process for the recycling and degradation of
      cellular materials. Forming the autophagosome from the phagophore, a cup-shaped
      double-membrane vesicle, is a critical step in autophagy. The origin of the cup
      shape of the phagophore is poorly understood. In yeast, fusion of a small number
      of Atg9-containing vesicles is considered a key step in autophagosome biogenesis,
      aided by Atg1 complexes (ULK1 in mammals) localized at the preautophagosomal
      structure (PAS). In particular, the S-shaped Atg17-Atg31-Atg29 subcomplex of Atg1
      is critical for phagophore nucleation at the PAS. To study this process, we
      simulated membrane remodeling processes in the presence and absence of membrane
      associated Atg17. We show that at least three vesicles need to fuse to induce the
      phagophore shape, consistent with experimental observations. However, fusion
      alone is not sufficient. Interactions with 34-nm long, S-shaped Atg17 complexes
      are required to overcome a substantial kinetic barrier in the transition to the
      cup-shaped phagophore. Our finding rationalizes the recruitment of Atg17
      complexes to the yeast PAS, and their unusual shape. In control simulations
      without Atg17, with weakly binding Atg17, or with straight instead of S-shaped
      Atg17, the membrane shape transition did not occur. We confirm the critical role
      of Atg17-membrane interactions experimentally by showing that mutations of
      putative membrane interaction sites result in reduction or loss of autophagic
      activity in yeast. Fusion of a small number of vesicles followed by Atg17-guided
      membrane shape-remodeling thus emerges as a viable route to phagophore formation.

PMID- 29065151
TI  - G protein-coupled estrogen receptor regulates embryonic heart rate in zebrafish.
AB  - Estrogens act by binding to estrogen receptors alpha and beta (ERalpha, ERbeta),
      ligand-dependent transcription factors that play crucial roles in sex
      differentiation, tumor growth and cardiovascular physiology. Estrogens also
      activate the G protein-coupled estrogen receptor (GPER), however the function of
      GPER in vivo is less well understood. Here we find that GPER is required for
      normal heart rate in zebrafish embryos. Acute exposure to estrogens increased
      heart rate in wildtype and in ERalpha and ERbeta mutant embryos but not in GPER
      mutants. GPER mutant embryos exhibited reduced basal heart rate, while heart rate
      was normal in ERalpha and ERbeta mutants. We detected gper transcript in discrete
      regions of the brain and pituitary but not in the heart, suggesting that GPER
      acts centrally to regulate heart rate. In the pituitary, we observed gper
      expression in cells that regulate levels of thyroid hormone triiodothyronine
      (T3), a hormone known to increase heart rate. Compared to wild type, GPER mutants
      had reduced levels of T3 and estrogens, suggesting pituitary abnormalities.
      Exposure to exogenous T3, but not estradiol, rescued the reduced heart rate
      phenotype in gper mutant embryos, demonstrating that T3 acts downstream of GPER
      to regulate heart rate. Using genetic and mass spectrometry approaches, we find
      that GPER regulates maternal estrogen levels, which are required for normal
      embryonic heart rate. Our results demonstrate that estradiol plays a previously
      unappreciated role in the acute modulation of heart rate during zebrafish
      embryonic development and suggest that GPER regulates embryonic heart rate by
      altering maternal estrogen levels and embryonic T3 levels.

PMID- 29065155
TI  - PRMT5: A novel regulator of Hepatitis B virus replication and an arginine
      methylase of HBV core.
AB  - In mammals, protein arginine methyltransferase 5, PRMT5, is the main type II
      enzyme responsible for the majority of symmetric dimethylarginine formation in
      polypeptides. Recent study reported that PRMT5 restricts Hepatitis B virus (HBV)
      replication through epigenetic repression of HBV DNA transcription and
      interference with encapsidation of pregenomic RNA. Here we demonstrate that PRMT5
      interacts with the HBV core (HBc) protein and dimethylates arginine residues
      within the arginine-rich domain (ARD) of the carboxyl-terminus. ARD consists of
      four arginine rich subdomains, ARDI, ARDII, ARDIII and ARDIV. Mutation analysis
      of ARDs revealed that arginine methylation of HBc required the wild-type status
      of both ARDI and ARDII. Mass spectrometry analysis of HBc identified multiple
      potential ubiquitination, methylation and phosphorylation sites, out of which
      lysine K7 and arginines R150 (within ARDI) and R156 (outside ARDs) were shown to
      be modified by ubiquitination and methylation, respectively. The HBc symmetric
      dimethylation appeared to be linked to serine phosphorylation and nuclear import
      of HBc protein. Conversely, the monomethylated HBc retained in the cytoplasm.
      Thus, overexpression of PRMT5 led to increased nuclear accumulation of HBc, and
      vice versa, down-regulation of PRMT5 resulted in reduced levels of HBc in nuclei
      of transfected cells. In summary, we identified PRMT5 as a potent controller of
      HBc cell trafficking and function and described two novel types of HBc post
      translational modifications (PTMs), arginine methylation and ubiquitination.

PMID- 29065157
TI  - Evaluating the efficiency of carbon utilisation via bioenergetics between
      biological aerobic and denitrifying phosphorus removal systems.
AB  - There are two biological systems available for removing phosphorus from waste
      water, conventional phosphorus removal (CPR) and denitrifying phosphorus removal
      (DPR) systems, and each is characterized by the type of sludge used in the
      process. In this study, we compared the characteristics associated with the
      efficiency of carbon utilization between CPR and DPR sludge using acetate as a
      carbon source. For DPR sludge, the heat emitted during the phosphorus release and
      phosphorus uptake processes were 45.79 kJ/mol e- and 84.09 kJ/mol e-,
      respectively. These values were about 2 fold higher than the corresponding values
      obtained for CPR sludge, suggesting that much of the energy obtained from the
      carbon source was emitted as heat. Further study revealed a smaller microbial
      mass within the DPR sludge compared to CPR sludge, as shown by a lower sludge
      yield coefficient (0.05 gVSS/g COD versus 0.36 gVSS/g COD), a result that was due
      to the lower energy capturing efficiency of DPR sludge according to bioenergetic
      analysis. Although the efficiency of anoxic phosphorus removal was only 39% the
      efficiency of aerobic phosphorus removal, the consumption of carbon by DPR sludge
      was reduced by 27.8% compared to CPR sludge through the coupling of
      denitrification with dephosphatation.

PMID- 29065156
TI  - Motor skill delays in pre-school children with leukemia one year after treatment:
      Hematopoietic stem cell transplantation therapy as an important risk factor.
AB  - CNS-directed therapies for the treatment of leukemia can adversely affect the
      acquisition of new skills, such as reading/writing and math. Two years after the
      end of treatments, children show gross and fine motor skill delays that may
      persist even when patients are considered healed. The goal of the present study
      was to assess motor skills difficulties in pre-school children with leukemia one
      year after treatment. Particular attention has been paid to those patients who
      had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the
      relationship between motor delays and age bands. Participants were 60 children
      (median age of 5; inter quartile range: 3.07-5.76), including 31 females and 29
      males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and
      8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents
      were interviewed by Vineland Adaptive Behavior Scales (VABS) on children's motor
      skills and filled in the Italian Temperament Questionnaire (QUIT). VABS's total
      scores were converted into equivalent mental age scores (EMA). A score difference
      of at least three months between current age and equivalent mental age was
      considered a developmental delay. Non-parametric analyses were run to understand
      if HSCT treatment and a specific age band influence children's motor skills.
      Significant delays were found in global motor skills (56.7%) as well as in fine
      and gross motor domains. Mann Whitney U tests showed that children with HSCT were
      reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank =
      15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on
      motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT
      Mean rank = 27.81). Kruskal Wallis' tests identified the high risk treatment
      showing that HSCT experience negatively impacted the motor skills and
      temperamental motor activity of pre-school children one year after the diagnosis
      of leukemia.

PMID- 29065158
TI  - Correction: Tetraspanin 6: A novel regulator of hippocampal synaptic transmission
      and long term plasticity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0171968.].

PMID- 29065160
TI  - Correction: Single Marker and Haplotype-Based Association Analysis of Semolina
      and Pasta Colour in Elite Durum Wheat Breeding Lines Using a High-Density
      Consensus Map.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0170941.].

PMID- 29065159
TI  - Cryopreserved rabbit amniotic membrane alleviated inflammatory response and
      fibrosis following experimental strabismus surgery in rabbits.
AB  - We evaluate the ability of cryopreserved rabbit amniotic membrane (AM)
      transplantation to reduce postoperative inflammation and the extent of fibrosis
      following experimental strabismus surgery. Ten white rabbits underwent bilateral
      superior rectus (SR) muscle resection. In the left eye, the resected SR muscle
      was wrapped with cryopreserved rabbit AM. The right eye underwent SR resection
      only and served as a control. The eyes were enucleated 4 weeks after strabismus
      surgery. The degree of postoperative inflammatory infiltration, the extent of
      fibrosis, and profile of the relative expression of inflammatory mediators in the
      SR muscle were evaluated and compared between the two groups by histological
      analysis and real-time polymerase chain reaction (PCR). There were statistically
      meaningful differences in the degree of postoperative inflammatory infiltration
      and extent of fibrosis between the eyes treated with cryopreserved rabbit AM
      after SR resection and those underwent SR resection only. A significant decrease
      in the expression of inflammatory cytokines [interleukin (IL)-12a, IL-12b, IL
      17f, and tumor necrosis factor- alpha (TNF-alpha)], and a markedly increased
      expression of anti-inflammatory cytokines (transforming growth factor-beta
      1(TGFbeta-1) and IL-10) were observed in the eyes treated with cryopreserved
      rabbit AM. In this study, we demonstrate that cryopreserved rabbit AM is
      effective in reducing postoperative inflammation and extent of fibrosis in a
      rabbit model of strabismus surgery. Our results imply that cryopreserved AM
      allograft has anti-inflammatory and anti-scarring properties that can prevent
      postoperative adhesions following strabismus surgery.

PMID- 29065161
TI  - Critical illness among adults with cystic fibrosis in Texas, 2004-2013: Patterns
      of ICU utilization, characteristics, and outcomes.
AB  - OBJECTIVE: Available reports on critically ill adults with cystic fibrosis (CF)
      suggest improving short-term outcomes. However, there is marked heterogeneity in
      reported findings, with studies mostly based on single-centered data, limiting
      generalizability. We sought to examine population-level patterns of demand for
      critical care resources, and the characteristics, resource utilization, and
      outcomes of ICU-managed adults with CF. METHODS: We used the Texas Inpatient
      Public Use Data File to identify ICU admissions with CF aged >=18 years in Texas
      between 2004-2013. We examined ICU utilization at population level (using CF
      Foundation annual reports) and, among ICU admissions, socio-demographic
      characteristics, burden of comorbidities, organ failure, life-support utilization
      and hospital disposition. Linear regression and multilevel logistic regression
      were used to examine temporal trends and predictors of short-term mortality
      (hospital death and discharge to hospice), respectively. RESULTS: Of 9,579
      hospitalizations of adults with CF, 1,249 (13%) were admitted to ICU. The
      incidence of ICU admission among adults with CF in Texas increased between 2004
      2005 and 2012-2013 from 16.7 to 19.2 per 100 person-years (p = 0.0181), with ICU
      admissions aged >=30 years accounting for 80.3% of the change. Among ICU
      admissions the following changes were noted between 2004-2005 and 2012-2013: any
      organ failure 30.2% vs. 56.3% (p = 0.0004), mechanical ventilation 11.5% vs.
      19.2% (p = 0.0216), and hemodialysis 1.0% vs. 8.1% (p = 0.0007). Short-term
      mortality for the whole cohort and for those with mechanical ventilation was
      11.4% and 41.8%, respectively, with corresponding home discharge among survivors
      84% and 62.1%, respectively. Key predictors (adjusted odds ratios [aOR (95% CI)])
      of short-term mortality included age >=45 years (2.051 [1.231-3.415]), female
      gender (1.907 [1.237-2.941]), and mechanical ventilation (7.982 [5.001-12.739]).
      CONCLUSIONS: Adults with CF had high and rising population-level burden of
      critical illness. Although ICU admissions were increasingly older and sicker, the
      majority survived hospitalization, with most discharged home, supporting short
      term benefits of critical care in the present cohort.

PMID- 29065162
TI  - Endosphere microbiome comparison between symptomatic and asymptomatic roots of
      Brassica napus infected with Plasmodiophora brassicae.
AB  - Clubroot caused by Plasmodiophora brassicae, is a severe disease of cruciferous
      crops that causes large hypertrophic galls in the roots. The plant microbiome is
      important for growth promotion and disease suppression. In this study, using 16S
      rRNA and internal transcribed spacer (ITS) sequencing techniques, we compared the
      endosphere microbiome of symptomatic and asymptomatic B. napus roots infected
      with P. brassicae collected from the same natural clubroot field. The results
      showed that the microbial population and its relative abundance in the
      asymptomatic roots was far higher than that in the symptomatic roots, and that
      many microorganisms in asymptomatic roots have biological control and plant
      growth promotion functions that may be related to clubroot symptoms. These
      results suggest the importance of the endosphere microbiome in clubroot disease
      and provide potential bio-control resources for its prevention.

PMID- 29065163
TI  - Drosophila VAMP7 regulates Wingless intracellular trafficking.
AB  - Drosophila Wingless (Wg) is a morphogen that determines cell fate during
      development. Previous studies have shown that endocytic pathways regulate Wg
      trafficking and signaling. Here, we showed that loss of vamp7, a gene required
      for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling.
      Interestingly, we found that levels of Dally-like (Dlp), a glypican that can
      interact with Wg to suppress Wg signaling at the dorsoventral boundary of the
      Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta
      in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that
      VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in
      Rab4-dependent recycling endosomes might affect Wg signaling.

PMID- 29065164
TI  - Oxygen uptake during functional activities after stroke-Reliability and validity
      of a portable ergospirometry system.
AB  - BACKGROUND: People with stroke have a low peak aerobic capacity and experience
      increased effort during performance of daily activities. The purpose of this
      study was to examine test-retest reliability of a portable ergospirometry system
      in people with stroke during performance of functional activities in a field
      test. Secondary aims were to examine the proportion of oxygen consumed during the
      field-test in relation to the peak-test and to analyse the correlation between
      the oxygen uptake during the field-test and peak-test in order to support the
      validity of the field-test. METHODS: With simultaneous measurement of oxygen
      consumption, participants performed a standardized field-test consisting of five
      activities; walking over ground, stair walking, stepping over obstacles, walking
      slalom between cones and from a standing position lifting objects from one height
      to another. All activities were performed in self-selected speed. Prior to the
      field-test, a peak aerobic capacity test was performed. The field-test was
      repeated minimum 2 and maximum 14 days between the tests. ICC2,1 and Bland Altman
      tests (Limits of Agreement, LoA) were used to analyse test-retest reliability.
      RESULTS: In total 31 participants (39% women, mean (SD) age 54.5 (12.7) years and
      21.1 (14.3) months' post-stroke) were included. The ICC2,1 was >= 0.80 for
      absolute VO2, relative VO2, minute ventilation, CO2, respiratory exchange ratio,
      heart rate and Borgs rating of perceived exertion. ICC2,1 for total time to
      complete the field-test was 0.99. Mean difference in steady state VO2 during Test
      1 and Test 2 was -0.40 (2.12) The LoAs were -3.75 and 4.51. Participants spent
      60.7% of their VO2peak performing functional activities. Correlation between
      field-test and peak-test was 0.689, p = 0.001 for absolute and 0.733, p = 0.001
      for relative VO2. CONCLUSIONS: This study presents first evidence on reliability
      of oxygen uptake during performance of functional activities after stroke,
      showing very good test-retest reliability. The secondary analysis showed that the
      amount of energy spent during the field-test relative to the peak-test was high
      and the correlation between the two test was good, supporting the validity of
      this method.

PMID- 29065165
TI  - Highly active antiretroviral therapy for critically ill HIV patients: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: It is unclear whether the treatment of an HIV infection with highly
      active antiretroviral therapy (HAART) affects intensive care unit (ICU) outcomes.
      In this paper, we report the results of a systematic review and meta-analysis
      performed to summarize the effects of HAART on the prognosis of critically ill
      HIV positive patients. MATERIALS AND METHODS: A bibliographic search was
      performed in 3 databases (PubMed, Web of Science and Scopus) to identify articles
      that investigated the use of HAART during ICU admissions for short- and long-term
      mortality or survival. Eligible articles were selected in a staged process and
      were independently assessed by two investigators. The methodological quality of
      the selected articles was evaluated using the Methodological Index for Non
      Randomized Studies (MINORS) tool. RESULTS: Twelve articles met the systematic
      review inclusion criteria and examined short-term mortality. Six of them also
      examined long-term mortality (>=90 days) after ICU discharge. The short-term
      mortality meta-analysis showed a significant beneficial effect of initiating or
      maintaining HAART during the ICU stay (random effects odds ratio 0.53, p = 0.02).
      The data analysis of long-term outcomes also suggested a reduced mortality when
      HAART was used, but the effect of HAART on long-term mortality of HIV positive
      critically ill patients remains uncertain. CONCLUSIONS: This meta-analysis
      suggests improved survival rates for HIV positive patients who were treated with
      HAART during their ICU admission.

PMID- 29065166
TI  - Genetic diversity and connectivity in the East African giant mud crab Scylla
      serrata: Implications for fisheries management.
AB  - The giant mud crab Scylla serrata provides an important source of income and food
      to coastal communities in East Africa. However, increasing demand and
      exploitation due to the growing coastal population, export trade, and tourism
      industry are threatening the sustainability of the wild stock of this species.
      Because effective management requires a clear understanding of the connectivity
      among populations, this study was conducted to assess the genetic diversity and
      connectivity in the East African mangrove crab S. serrata. A section of 535 base
      pairs of the cytochrome oxidase subunit I (COI) gene and eight microsatellite
      loci were analysed from 230 tissue samples of giant mud crabs collected from
      Kenya, Tanzania, Mozambique, Madagascar, and South Africa. Microsatellite genetic
      diversity (He) ranged between 0.56 and 0.6. The COI sequences showed 57 different
      haplotypes associated with low nucleotide diversity (current nucleotide diversity
      = 0.29%). In addition, the current nucleotide diversity was lower than the
      historical nucleotide diversity, indicating overexploitation or historical
      bottlenecks in the recent history of the studied population. Considering that the
      coastal population is growing rapidly, East African countries should promote
      sustainable fishing practices and sustainable use of mangrove resources to
      protect mud crabs and other marine fauna from the increasing pressure of
      exploitation. While microsatellite loci did not show significant genetic
      differentiation (p > 0.05), COI sequences revealed significant genetic divergence
      between sites on the East coast of Madagascar (ECM) and sites on the West coast
      of Madagascar, mainland East Africa, as well as the Seychelles. Since East
      African countries agreed to achieve the Convention on Biological Diversity (CBD)
      target to protect over 10% of their marine areas by 2020, the observed pattern of
      connectivity and the measured genetic diversity can serve to provide useful
      information for designing networks of marine protected areas.

PMID- 29065168
TI  - Evaluation of AISI Type 304 stainless steel as a suitable surface material for
      evaluating the efficacy of peracetic acid-based disinfectants against Clostridium
      difficile spores.
AB  - Disinfectants play an important role in controlling microbial contamination on
      hard surfaces in hospitals. The effectiveness of disinfectants in real life can
      be predicted by laboratory tests that measure killing of microbes on carriers.
      The modified Quantitative Disk Carrier Test (QCT-2) is a standard laboratory
      method that employs American Iron and Steel Institute (AISI) Type 430 stainless
      steel carriers to measure hospital disinfectant efficacy against Clostridium
      difficile spores. The formation of a rust-colored precipitate was observed on
      Type 430 carriers when testing a peracetic acid (PAA)-based disinfectant with the
      QCT-2 method. It was hypothesized that the precipitate was indicative of
      corrosion of the Type 430 carrier, and that corrosion could impact efficacy
      results. The objective of this study was to compare the suitability of AISI Type
      430 to Type 304 stainless steel carriers for evaluating PAA-based disinfectants
      using the QCT-2 method. Type 304 is more corrosion-resistant than Type 430, is
      ubiquitous in healthcare environments, and is used in other standard methods.
      Suitability of the carriers was evaluated by comparing their impacts on efficacy
      results and PAA degradation rates. In efficacy tests with 1376 ppm PAA,
      reductions of C. difficile spores after 5, 7 and 10 minutes on Type 430 carriers
      were at least about 1.5 log10 lower than reductions on Type 304 carriers. In
      conditions simulating a QCT-2 test, PAA concentration with Type 430 carriers was
      reduced by approximately 80% in 10 minutes, whereas PAA concentration in the
      presence of Type 304 carriers remained stable. Elemental analyses of residues on
      each carrier type after efficacy testing were indicative of corrosion on the Type
      430 carrier. Use of Type 430 stainless steel carriers for measuring the efficacy
      of PAA-based disinfectants should be avoided as it can lead to an underestimation
      of real life sporicidal efficacy. Type 304 stainless steel carriers are
      recommended as a suitable alternative.

PMID- 29065167
TI  - Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a highly debilitating disease of unknown
      aetiology. Abnormalities in bioenergetic function have been cited as one possible
      cause for CFS. Preliminary studies were performed to investigate cellular
      bioenergetic abnormalities in CFS patients. A series of assays were conducted
      using peripheral blood mononuclear cells (PBMCs) from CFS patients and healthy
      controls. These experiments investigated cellular patterns in oxidative
      phosphorylation (OXPHOS) and glycolysis. Results showed consistently lower
      measures of OXPHOS parameters in PBMCs taken from CFS patients compared with
      healthy controls. Seven key parameters of OXPHOS were calculated: basal
      respiration, ATP production, proton leak, maximal respiration, reserve capacity,
      non-mitochondrial respiration, and coupling efficiency. While many of the
      parameters differed between the CFS and control cohorts, maximal respiration was
      determined to be the key parameter in mitochondrial function to differ between
      CFS and control PBMCs due to the consistency of its impairment in CFS patients
      found throughout the study (p<=0.003). The lower maximal respiration in CFS PBMCs
      suggests that when the cells experience physiological stress they are less able
      to elevate their respiration rate to compensate for the increase in stress and
      are unable to fulfil cellular energy demands. The metabolic differences
      discovered highlight the inability of CFS patient PBMCs to fulfil cellular
      energetic demands both under basal conditions and when mitochondria are stressed
      during periods of high metabolic demand.

PMID- 29065169
TI  - Demographics and practices of semi-intensive free-range farming systems in
      Australia with an outdoor stocking density of <=1500 hens/hectare.
AB  - Baseline information on demographics and practices on semi-intensive free-range
      egg farms with an outdoor stocking density of <=1500 hens/hectare in Australia is
      presented. Free-range egg production is changing the structure of the egg
      industry in Australia and a broad variety and tiers of free-range systems have
      emerged due to lack of concrete legislative standards on outdoor stocking
      densities in the past. Information was extracted from a pre-existing online free
      range poultry survey dataset, consisting of a total of 79 questions related to
      nutrition, pasture management, welfare and health, animal housing, environmental
      impact and economics. Forty-one free-range egg farms, with an outdoor stocking
      density of <=1500 hens/hectare, were identified in the dataset from all major
      Australian states. Two types of semi-intensive free-range housing systems were
      documented: mobile (modified caravan/trailer) housing (56%), and fixed sheds
      (44%). Seventy-two percent of respondents reported >75% of the hens in the flock
      used the outdoor range. All respondents reported ingestion of range components by
      hens in the form of vegetation, insects, stones and grit. Up to 10% mortality was
      reported by 40% respondents with predation (34%), cannibalism (29%), heat stress
      (24%) and grass impaction (19.5%) as major causes. Biosecurity on farms was sub
      optimal with 8 of the 10 actions implemented by <50% respondents. Customer
      demand, consumer sentiment and welfare were the major factors for farmers moving
      into free-range egg production. This study resulted in identification of current
      practices and key challenges on semi-intensive free-range egg farms. Applied
      research and communication of results to farmers is highly recommended to ensure
      optimum health and welfare of free-range laying hens and sustained egg
      production.

PMID- 29065170
TI  - Zinc-finger protein 418 overexpression protects against cardiac hypertrophy and
      fibrosis.
AB  - BACKGROUND: This study aimed to investigated the effect and mechanism of zinc
      finger protein 418 (ZNF418) on cardiac hypertrophy caused by aortic banding (AB),
      phenylephrine (PE) or angiotensin II (Ang II) in vivo and in vitro. METHODS: The
      expression of ZNF418 in hearts of patients with dilated cardiomyopathy (DCM) or
      hypertrophic cardiomyopathy (HCM) and AB-induced cardiac hypertrophy mice, as
      well as in Ang II- or PE-induced hypertrophic primary cardiomyocytes was detected
      by western blotting. Then, the expression of ZNF418 was up-regulated or down
      regulated in AB-induced cardiac hypertrophy mice and Ang II -induced hypertrophic
      primary cardiomyocytes. The hypertrophic responses and fibrosis were evaluated by
      echocardiography and histological analysis. The mRNA levels of hypertrophy
      markers and fibrotic markers were detected by RT-qPCR. Furthermore, the
      phosphorylation and total levels of c-Jun were measured by western blotting.
      RESULTS: ZNF418 was markedly down-regulated in hearts of cardiac hypertrophy and
      hypertrophic primary cardiomyocytes. Down-regulated ZNF418 exacerbated the
      myocyte size and fibrosis, moreover increased the mRNA levels of ANP, BNP, beta
      MHC, MCIP1.4, collagen 1a, collagen III, MMP-2 and fibronection in hearts of AB
      treated ZNF418 knockout mice or Ang II-treated cardiomyocytes with AdshZNF418.
      Conversely, these hypertrophic responses were reduced in the ZNF418 transgenic
      (TG) mice treated by AB and the AdZNF418-transfected primary cardiomyocytes
      treated by Ang II. Additionally, the deficiency of ZNF418 enhanced the
      phosphorylation level of c-jun, and overexpression of ZNF418 suppressed the
      phosphorylation level of c-jun in vivo and in vitro. CONCLUSION: ZNF418 maybe
      attenuate hypertrophic responses by inhibiting the activity of c-jun/AP-1.

PMID- 29065171
TI  - Alleviatory effects of silicon on the foliar micromorphology and anatomy of rice
      (Oryza sativa L.) seedlings under simulated acid rain.
AB  - Silicon (Si) is a macroelement in plants. The biological effects and mitigation
      mechanisms of silicon under environmental stress have become hot topics. The main
      objectives of this study were to elucidate the roles of Si in alleviating the
      effects on the phenotype, micromorphology and anatomy of the leaves of rice
      seedlings under acid rain stress. The results indicated that the combined or
      single effects of Si and simulated acid rain (SAR) stress on rice roots depended
      on the concentration of Si and the intensity of the SAR stress. The combined or
      single effects of the moderate concentration of Si (2.0 mM) and light SAR (pH
      4.0) enhanced the growth of the rice leaves and the development of the mesophyll
      cells, and the combined effects were stronger than those of the single
      treatments. The high concentration of Si (4.0 mM) and severe SAR (pH 3.0 or 2.0)
      exerted deleterious effects. The incorporation of Si (2.0 or 4.0 mM) into SAR at
      pH values of 3.0 or 2.0 promoted rice leaf growth, decreased necrosis spots,
      maintained the structure and function of the mesophyll cells, increased the
      epicuticular wax content and wart-like protuberance (WP) density, and improved
      the stomatal characteristics of the leaves of rice seedlings more than the SAR
      only treatments. The alleviatory effects observed with a moderate concentration
      of Si (2.0 mM) were better than the effects obtained with the high concentration
      of Si (4.0 mM). The alleviatory effects were due to the enhancement of the
      mechanical barriers in the leaf epidermis.

PMID- 29065173
TI  - New nonlinear model of population growth.
AB  - The model of population growth is revised in this paper. A new model is proposed
      based on the concept of fractional differentiation that uses the generalized
      Mittag-Leffler function as kernel of differentiation. The new model includes the
      choice of sexuality. The existence of unique solution is investigated and
      numerical solution is provided.

PMID- 29065172
TI  - Concomitant nevirapine impacts pharmacokinetic exposure to the antimalarial
      artemether-lumefantrine in African children.
AB  - BACKGROUND: The antiretroviral drug nevirapine and the antimalarial artemisinin
      based combination therapy artemether-lumefantrine are commonly co-administered to
      treat malaria in the context of HIV. Nevirapine is a known inhibitor of
      cytochrome P450 3A4, which metabolizes artemether and lumefantrine. To address
      the concern that the antiretroviral nevirapine impacts the antimalarial
      artemether-lumefantrine pharmacokinetics, a prospective non-randomized controlled
      study in children presenting with uncomplicated malaria and HIV in sub-Saharan
      Africa was carried out. METHODS: Participants received artemether-lumefantrine
      (20/120 mg weight-based BID) for 3 days during nevirapine-based antiretroviral
      therapy (ART) co-administration (158-266 mg/m2 QD). HIV positive participants who
      were not yet on ART drugs were also enrolled as the control group. The target
      enrollment was children aged 3-12 years (n = 24 in each group). Intensive
      pharmacokinetics after the last artemether-lumefantrine dose was assessed for
      artemether, its active metabolite dihydroartemisinin, and lumefantrine.
      Pharmacokinetic parameters (area under the plasma concentration vs. time curve
      (AUC), maximum concentration and day 7 lumefantrine concentrations) were
      estimated using non-compartmental methods and compared to controls. RESULTS:
      Nineteen children (16 on nevirapine and three not on ART) enrolled. Fifteen of
      the 16 (aged 4 to 11 years) on nevirapine-based ART were included in the
      pharmacokinetic analysis. Due to evolving WHO HIV treatment guidelines,
      insufficient children were enrolled in the control group (n = 3), so the
      pharmacokinetic data were compared to a historical control group of 20 HIV
      uninfected children 5-12 years of age who also presented with malaria and
      underwent identical study procedures. Decreases of pharmacokinetic exposure [as
      estimated by AUC (AUC0-8hr)] were marginally significant for artemether (by -46%,
      p = 0.08) and dihydroartemisinin (-22%, p = 0.06) in the children on nevirapine
      based ART, compared to when artemether-lumefantrine was administered alone.
      Similarly, peak concentration was decreased by 50% (p = 0.07) for artemether and
      36% (p = 0.01) for dihydroartemisinin. In contrast, exposure to lumefantrine
      increased significantly in the context of nevirapine [AUC0-120hr:123% (p<0.001);
      Cday7:116% (p<0.001), Cmax: 95% (p<0.001)]. CONCLUSIONS: Nevirapine-based ART
      increases the exposure to lumefantrine in pre-pubescent children with a trend
      toward diminished artemether and dihydroartemisinin exposure. These findings
      contrast with other studies indicating NVP reduces or results in no change in
      exposure of antimalarial drugs, and may be specific to this age group (4-12
      years). Considering the excellent safety profile of artemether-lumefantrine, the
      increase in lumefantrine is not of concern. However, the reduction in artemisinin
      exposure may warrant further study, and suggests that dosage adjustment of
      artemether-lumefantrine with nevirapine-based ART in children is likely
      warranted.

PMID- 29065174
TI  - Glucagon like receptor 1/ glucagon dual agonist acutely enhanced hepatic lipid
      clearance and suppressed de novo lipogenesis in mice.
AB  - Lipid lowering properties of glucagon have been reported. Blocking glucagon
      signaling leads to rise in plasma LDL levels. Here, we demonstrate the lipid
      lowering effects of acute dosing with Glp1r/Gcgr dual agonist (DualAG). All the
      experiments were performed in 25 week-old male diet-induced (60% kCal fat) obese
      mice. After 2 hrs of fasting, mice were injected subcutaneously with vehicle,
      liraglutide (25nmol/kg) and DualAG (25nmol/kg). De novo cholesterol and palmitate
      synthesis was measured by deuterium incorporation method using D2O. 13C18-oleate
      infusion was used for measuring fatty acid esterification. Simultaneous
      activation of Glp1r and Gcgr resulted in decrease in plasma triglyceride and
      cholesterol levels. DualAG enhanced hepatic LDLr protein levels, along with
      causing decrease in content of plasma ApoB48 and ApoB100. VLDL secretion, de novo
      palmitate synthesis and fatty acid esterification decreased with acute DualAG
      treatment. On the other hand, ketone levels were elevated with DualAG treatment,
      indicating increased fatty acid oxidation. Lipid relevant changes were absent in
      liraglutide treated group. In an acute treatment, DualAG demonstrated significant
      impact on lipid homeostasis, specifically on hepatic uptake, VLDL secretion and
      de novo synthesis. These effects collectively reveal that lipid lowering
      abilities of DualAG are primarily through glucagon signaling and are liver
      centric.

PMID- 29065175
TI  - Comparative analysis of activation induced marker (AIM) assays for sensitive
      identification of antigen-specific CD4 T cells.
AB  - The identification and study of antigen-specific CD4 T cells, both in peripheral
      blood and in tissues, is key for a broad range of immunological research,
      including vaccine responses and infectious diseases. Detection of these cells is
      hampered by both their rarity and their heterogeneity, in particular with regards
      to cytokine secretion profiles. These factors prevent the identification of the
      total pool of antigen-specific CD4 T cells by classical methods. We have
      developed assays for the highly sensitive detection of such cells by measuring
      the upregulation of surface activation induced markers (AIM). Here, we compare
      two such assays based on concurrent expression of CD69 plus CD40L (CD154) or
      expression of OX40 plus CD25, and we develop additional AIM assays based on OX40
      plus PD-L1 or 4-1BB. We compare the relative sensitivity of these assays for
      detection of vaccine and natural infection-induced CD4 T cell responses and show
      that these assays identify distinct, but overlapping populations of antigen
      specific CD4 T cells, a subpopulation of which can also be detected on the basis
      of cytokine synthesis. Bystander activation had minimal effect on AIM markers.
      However, some T regulatory cells upregulate CD25 upon antigen stimulation. We
      therefore validated AIM assays designed to exclude most T regulatory cells, for
      both human and non-human primate (NHP, Macaca mulatta) studies. Overall, through
      head-to-head comparisons and methodological improvements, we show that AIM assays
      represent a sensitive and valuable method for the detection of antigen-specific
      CD4 T cells.

PMID- 29065176
TI  - Genome-wide analysis of structural variants reveals genetic differences in
      Chinese pigs.
AB  - Pigs have experienced long-term selections, resulting in dramatic phenotypic
      changes. Structural variants (SVs) are reported to exert extensive impacts on
      phenotypic changes. We built a high resolution and informative SV map based on
      high-depth sequencing data from 66 Chinese domestic and wild pigs. We inferred
      the SV formation mechanisms in the pig genome and used SVs as materials to
      perform a population-level analysis. We detected the selection signals on
      chromosome X for northern Chinese domestic pigs, as well as the differentiated
      loci across the whole genome. Analysis showed that these loci differ between
      southern and northern Chinese domestic pigs. Our results based on SVs provide new
      insights into genetic differences in Chinese pigs.

PMID- 29065177
TI  - miR-27a induced by colon cancer cells in HLECs promotes lymphangiogenesis by
      targeting SMAD4.
AB  - AIM: Metastasis of tumor cells occurs through lymphatic vessels, blood vessels
      and transcoelomic spreading. Growing evidence from in vivo and in vitro studies
      has indicated that tumor lymphangiogenesis facilitates metastasis. However, the
      regulation of lymphangiogenesis in colon cancer remains unclear. The aims of this
      study were to identify key miRNAs in colon cancer lymphangiogenesis and to
      investigate its target and mechanism. METHODS: miRNA microarray analysis was
      conducted to identify miRNAs in human lymphatic endothelial cells (HLECs) that
      were regulated by co-cultured human colon cancer cells. Gain- and loss-of
      function studies were performed to determine the function of miR-27a, a top hint,
      on lymphangiogenesis and migration in HLECs. Furthermore, bioinformatics
      prediction and experimental validation were performed to identify miR-27a target
      genes in lymphangiogenesis. RESULTS: We found that expression of miR-27a in HLECs
      was induced by co-culturing with colon cancer cells. Over-expression of miR-27a
      in HLECs enhanced lymphatic tube formation and migration, whereas inhibition of
      miR-27a reduced lymphatic tube formation and migration. Luciferase reporter
      assays showed that miR-27a directly targeted SMAD4, a pivotal component of the
      TGF-beta pathway. In addition, gain-of-function and loss-of-function experiments
      showed that SMAD4 negatively regulated the length of lymphatic vessels formed by
      HLECs and migration. CONCLUSIONS: Our data indicated that colon cancer cell
      induced the expression of miR-27a in HLECs, which promoted lymphangiogenesis by
      targeting SMAD4. Our finding implicated miR-27a as a potential target for new
      anticancer therapies in colon cancer.

PMID- 29065178
TI  - Intravital imaging of osteocytes in mouse calvaria using third harmonic
      generation microscopy.
AB  - Osteocytes are the most abundant cell in the bone, and have multiple functions
      including mechanosensing and regulation of bone remodeling activities. Since
      osteocytes are embedded in the bone matrix, their inaccessibility makes in vivo
      studies problematic. Therefore, a non-invasive technique with high spatial
      resolution is desired. The purpose of this study is to investigate the use of
      third harmonic generation (THG) microscopy as a noninvasive technique for high
      resolution imaging of the lacunar-canalicular network (LCN) in live mice. By
      performing THG imaging in combination with two- and three-photon fluorescence
      microscopy, we show that THG signal is produced from the bone-interstitial fluid
      boundary of the lacuna, while the interstitial fluid-osteocyte cell boundary
      shows a weaker THG signal. Canaliculi are also readily visualized by THG imaging,
      with canaliculi oriented at small angles relative to the optical axis exhibiting
      stronger signal intensity compared to those oriented perpendicular to the optical
      axis (parallel to the image plane). By measuring forward- versus epi-detected THG
      signals in thinned versus thick bone samples ex vivo, we found that the epi
      collected THG from the LCN of intact bone contains a superposition of backward
      directed and backscattered forward-THG. As an example of a biological
      application, THG was used as a label-free imaging technique to study structural
      variations in the LCN of live mice deficient in both histone deacetylase 4 and 5
      (HDAC4, HDAC5). Three-dimensional analyses were performed and revealed
      statistically significant differences between the HDAC4/5 double knockout and
      wild type mice in the number of osteocytes per volume and the number of
      canaliculi per lacunar surface area. These changes in osteocyte density and
      dendritic projections occurred without differences in lacunar size. This study
      demonstrates that THG microscopy imaging of the LCN in live mice enables
      quantitative analysis of osteocytes in animal models without the use of dyes or
      physical sectioning.

PMID- 29065179
TI  - Comparative proteome and peptidome analysis of the cephalic fluid secreted by
      Arapaima gigas (Teleostei: Osteoglossidae) during and outside parental care.
AB  - Parental investment in Arapaima gigas includes nest building and guarding,
      followed by a care provision when a cephalic fluid is released from the parents'
      head to the offspring. This fluid has presumably important functions for the
      offspring but so far its composition has not been characterised. In this study
      the proteome and peptidome of the cephalic secretion was studied in parental and
      non-parental fish using capillary electrophoresis coupled to mass spectrometry
      (CE-MS) and GeLC-MS/MS analyses. Multiple comparisons revealed 28 peptides were
      significantly different between males and parental males (PC-males), 126 between
      females and parental females (PC-females), 51 between males and females and 9
      between PC-males and PC-females. Identification revealed peptides were produced
      in the inner ear (pcdh15b), eyes (tetraspanin and ppp2r3a), central nervous
      system (otud4, ribeye a, tjp1b and syn1) among others. A total of 422 proteins
      were also identified and gene ontology analysis revealed 28 secreted
      extracellular proteins. From these, 2 hormones (prolactin and stanniocalcin) and
      12 proteins associated to immunological processes (serotransferrin, alpha-1
      antitrypsin homolog, apolipoprotein A-I, and others) were identified. This study
      provides novel biochemical data on the lateral line fluid which will enable
      future hypotheses-driven experiments to better understand the physiological roles
      of the lateral line in chemical communication.

PMID- 29065181
TI  - Chloroplast genomes of Lilium lancifolium, L. amabile, L. callosum, and L.
      philadelphicum: Molecular characterization and their use in phylogenetic analysis
      in the genus Lilium and other allied genera in the order Liliales.
AB  - Chloroplast (cp) genomes of Lilium amabile, L. callosum, L. lancifolium, and L.
      philadelphicum were fully sequenced. Using these four novel cp genome sequences
      and five other previously sequenced cp genomes, features of the cp genomes were
      characterized in detail among species in the genus Lilium and other related
      genera in the order Liliales. The lengths and nucleotide composition showed
      little variation. No structural variation was found among the cp genomes in
      Liliales. Gene contents were conserved among four newly sequenced cp genome in
      Lilium species, the only differences being in two pseudogenes. We identified 112
      genes in 13 functional categories, 18 of which carried introns that were
      conserved among the species in Liliales. There were 16-21 SSR loci (>12 bp, >3
      repeats) in the cp genomes in Lilium and the genomic locations of these loci were
      highly variable among the species. Average mutations were 15 SNPs per 1kb and 5
      indels per 1kb, respectively, in the cp genomes of the newly sequenced four
      Lilium species. Phylogenetic classifications revealed some discrepancies between
      trees based on the cp genomes and previous classifications based on the
      morphology and geographic distributions.

PMID- 29065180
TI  - Hepcidin in morbidly obese women with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of
      chronic liver disease in Western countries. Both iron and lipid metabolism seem
      to be involved in its pathogenesis. We aimed to assess the relationship between
      levels of hepcidin, the master iron-regulatory protein, in plasma and the
      presence of NAFLD in morbidly obese (MO) patients, and to investigate the
      association between the hepatic expression of the main iron and lipid metabolism 
      related genes. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay was used
      to measure plasma hepcidin levels in 49 normal-weight control women, 23 MO women
      with normal liver (NL) histology and 46 MO women with NAFLD. The mRNA expression
      of hepcidin, the main iron metabolism-related genes, and the main lipid
      metabolism genes was quantified by qRT-PCR in liver biopsies from members of the
      MO group undergoing bariatric surgery. RESULTS: Circulating hepcidin levels were
      significantly greater in MO than in normal-weight control women. However, there
      were no significant differences between MO women with NL and those with NAFLD.
      PCR analysis showed increased expression of hepcidin, FPN1, TfR1 and TfR2 in the
      liver of MO NAFLD women compared to those with NL. Moreover, a positive
      association of hepatic hepcidin mRNA expression and the iron metabolism-related
      genes was found with some key genes involved in the lipid metabolism. CONCLUSION:
      These findings suggest that circulating hepcidin levels are associated with
      obesity but not with the presence of NAFLD. However, the hepatic expression of
      hepcidin and the iron metabolism-related genes seem to play a role in regulating
      lipid metabolism pathways in liver, which has implications for NAFLD
      pathogenesis.

PMID- 29065182
TI  - Clinical characterization of acute and convalescent illness of confirmed
      chikungunya cases from Chiapas, S. Mexico: A cross sectional study.
AB  - BACKGROUND: The emerging chikungunya virus (CHIKV), is an arbovirus causing
      intense outbreaks in North America. The situation in Mexico is alarming, and
      CHIKV threatens to spread further throughout North America. Clinical and
      biological features of CHIKF outbreaks in Mexico have not been well described;
      thus, we conducted a cross sectional study of a CHIKV outbreak in Chiapas,
      Southern Mexico to further characterize these features. METHODOLOGY/PRINCIPAL
      FINDINGS: We collected blood samples from patients suspected of having
      chikungunya fever (CHIKF) who presented to Clinical Hospital ISSSTE Dr. Roberto
      Nettel in Tapachula, Chiapas, Mexico. In addition to the clinical examination,
      real-time polymerase chain reaction (PCR) standardized for the Asian Chikungunya
      lineage and/or enzyme-linked immunosorbent assay for immunoglobulin M (IgM) were
      used to confirm CHIKV diagnosis. Of a total of 850 patients who presented with
      probably CHIKV at Hospital "Dr. Roberto Nettel", 112 probable CHIKF cases were
      enrolled in this study from November 2014- June 2015, of which 95 patients
      (84.8%) were CHIKV positive and 17 were negative (15.2%). Of these 95 CHIKV
      positive patients, 62 were positive by real-time reverse transcriptase PCR (+qRT
      PCR); and 33 were seropositive to +IgM with a negative qRT-PCR. The most frequent
      symptoms reported were fever (100%), headache (82.3%), polyarthralgia (72.1%),
      and exanthem (82.3%). Biological abnormalities observed during CHIKV infection
      were lymphopenia (41.1%), leukopenia (51.6%), elevated transaminases (30.5%
      46.3%) and high LDH (46.3%) and CRP (60.0%). CONCLUSION: Clinical and biological
      data obtained from this study is providing more useful information for
      benchmarking purposes with outbreaks from different parts of the world and would
      be helpful for better patient care and treatment.

PMID- 29065183
TI  - An electroporation-free method based on Red recombineering for markerless
      deletion and genomic replacement in the Escherichia coli DH1 genome.
AB  - The lambda-Red recombination system is a popular method for gene editing.
      However, its applications are limited due to restricted electroporation of DNA
      fragments. Here, we present an electroporation-free lambda-Red recombination
      method in which target DNA fragments are excised by I-CreI endonuclease in vivo
      from the landing pad plasmid. Subsequently, the I-SceI endonuclease-cutting
      chromosome and DNA double-strand break repair were required. Markerless deletion
      and genomic replacement were successfully accomplished by this novel approach.
      Eight nonessential regions of 2.4-104.4 kb in the Escherichia coli DH1 genome
      were deleted separately with selection efficiencies of 5.3-100%. Additionally,
      the recombination efficiencies were 2.5-45%, representing an order of magnitude
      improvement over the electroporation method. For example, for genomic
      replacement, lycopene expression flux (3.5 kb) was efficiently and precisely
      integrated into the chromosome, accompanied by replacement of nonessential
      regions separately into four differently oriented loci. The lycopene production
      level varied approximately by 5- and 10-fold, corresponding to the integrated
      position and expression direction, respectively, in the E. coli chromosome.

PMID- 29065185
TI  - Gonadal cycle of Corbicula fluminea (Bivalvia: Corbiculidae) in Pampean streams
      (Southern Neotropical Region).
AB  - Corbicula fluminea is an aggressive invasive species of bivalve that arrived into
      the Rio de la Plata River between the late 60's and early 70's, and dispersed
      widely throughout the Neotropical region, evidencing a great adaptive flexibility
      to different environmental conditions. This species is a functional hermaphrodite
      with larval incubation inside the inner demibranch. Despite its widespread
      distribution, there are no previous studies of complete gonadal histology and
      reproductive cycle for this species in the Neotropical region. In this study, the
      reproductive dynamics of C. fluminea in a temperate region, the Santa Catalina
      Pampean stream, Argentina, is described. Samples of 20-30 individuals were
      collected monthly from April 2003-April 2005 and processed using traditional
      histological techniques. During the two years of this study, seven spawning
      events were recognized. Three major spawns occurred in spring and summer, and
      other four minor ones during summer and autumn. Events of oocyte recovery were
      observed after spawning. A high number of incubating individuals was detected.
      The results stressed the difficulty of identifying a particular pattern of gamete
      release and of spawning behaviour in this invasive species, especially when
      inhabiting an unstable environment.

PMID- 29065186
TI  - Environmental risk of leptospirosis infections in the Netherlands: Spatial
      modelling of environmental risk factors of leptospirosis in the Netherlands.
AB  - Leptospirosis is a globally emerging zoonotic disease, associated with various
      climatic, biotic and abiotic factors. Mapping and quantifying geographical
      variations in the occurrence of leptospirosis and the surrounding environment
      offer innovative methods to study disease transmission and to identify
      associations between the disease and the environment. This study aims to
      investigate geographic variations in leptospirosis incidence in the Netherlands
      and to identify associations with environmental factors driving the emergence of
      the disease. Individual case data derived over the period 1995-2012 in the
      Netherlands were geocoded and aggregated by municipality. Environmental covariate
      data were extracted for each municipality and stored in a spatial database.
      Spatial clusters were identified using kernel density estimations and quantified
      using local autocorrelation statistics. Associations between the incidence of
      leptospirosis and the local environment were determined using Simultaneous
      Autoregressive Models (SAR) explicitly modelling spatial dependence of the model
      residuals. Leptospirosis incidence rates were found to be spatially clustered,
      showing a marked spatial pattern. Fitting a spatial autoregressive model
      significantly improved model fit and revealed significant association between
      leptospirosis and the coverage of arable land, built up area, grassland and
      sabulous clay soils. The incidence of leptospirosis in the Netherlands could
      effectively be modelled using a combination of soil and land-use variables
      accounting for spatial dependence of incidence rates per municipality. The
      resulting spatially explicit risk predictions provide an important source of
      information which will benefit clinical awareness on potential leptospirosis
      infections in endemic areas.

PMID- 29065184
TI  - Do all inhibitions act alike? A study of go/no-go and stop-signal paradigms.
AB  - Response inhibition is frequently measured by the Go/no-go and Stop-signal tasks.
      These two are often used indiscriminately under the assumption that both measure
      similar inhibitory control abilities. However, accumulating evidence show
      differences in both tasks' modulations, raising the question of whether they tap
      into equivalent cognitive mechanisms. In the current study, a comparison of the
      performance in both tasks took place under the influence of negative stimuli,
      following the assumption that ''controlled inhibition'', as measured by Stop
      signal, but not ''automatic inhibition'', as measured by Go/no-go, will be
      affected. 54 young adults performed a task in which negative pictures, neutral
      pictures or no-pictures preceded go trials, no-go trials, and stop-trials. While
      the exposure to negative pictures impaired performance on go trials and improved
      the inhibitory capacity in Stop-signal task, the inhibitory performance in Go/no
      go task was generally unaffected. The results support the conceptualization of
      different mechanisms operated by both tasks, thus emphasizing the necessity to
      thoroughly fathom both inhibitory processes and identify their corresponding
      cognitive measures. Implications regarding the usage of cognitive tasks for
      strengthening inhibitory capacity among individuals struggling with inhibitory
      impairments are discussed.

PMID- 29065187
TI  - Prognostic value of sarcopenia in patients with liver cirrhosis: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Sarcopenia is a common syndrome in chronic diseases such as liver
      cirrhosis. The association between sarcopenia and outcomes, such as complications
      and survival has recently been described in various patient groups. However,
      study results remain inconclusive. Therefore, the aim of this study was to
      systematically review the impact of sarcopenia on outcome in patients with
      cirrhosis. METHODS AND FINDINGS: We conducted a systematic review (SR) and meta
      analysis (MA) on the impact of sarcopenia on outcome in liver cirrhosis was
      performed according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analysis guidelines. Of the 312 studies identified, 20 were eligible
      according to our inclusion criteria. Most of the studies used CT to diagnose
      sarcopenia. Two studies used bioelectrical impedance analysis (BIA), 10 studies
      used skeletal muscle index (SMI) and 8 studies used total psoas muscle area
      (TPA). Seven studies included Asian participants and the remaining 13 studies
      included Western participants. The prevalence rate of sarcopenia among
      participants was mean 48.1%, and appeared more among men with a rate of 61.6%
      whereas the rate was 36% for women. With respect to clinical outcomes, patients
      with sarcopenia had poorer survival rates and an increased risk of complications
      such as infection compared to those without sarcopenia. According to the analysis
      of race subgroup, Asians had a HR 2.45 (95% confidence interval (CI) = 1.44-4.16,
      P = 0.001) of mortality whereas Westerners had a HR 1.45 (95% CI = 1.002-2.09,
      P<0.05). CONCLUSIONS: Based on this SR and MA, the presence of sarcopenia is
      related to a poor prognosis and occurrence of cirrhotic complications and could
      be used for risk assessment. Moreover, Asian participants had higher mortality
      related to sarcopenia compared to the Western participants.

PMID- 29065188
TI  - Seasonal effects of wind conditions on migration patterns of soaring American
      white pelican.
AB  - Energy and time expenditures are determinants of bird migration strategies.
      Soaring birds have developed migration strategies to minimize these costs,
      optimizing the use of all the available resources to facilitate their
      displacement. We analysed the effects of different wind factors (tailwind,
      turbulence, vertical updrafts) on the migratory flying strategies adopted by 24
      satellite-tracked American white pelicans (Pelecanus erythrorhynchos) throughout
      spring and autumn in North America. We hypothesize that different wind conditions
      encountered along migration routes between spring and autumn induce pelicans to
      adopt different flying strategies and use of these wind resources. Using quantile
      regression and fine-scale atmospheric data, we found that the pelicans optimized
      the use of available wind resources, flying faster and more direct routes in
      spring than in autumn. They actively selected tailwinds in both spring and autumn
      displacements but relied on available updrafts predominantly in their spring
      migration, when they needed to arrive at the breeding regions. These effects
      varied depending on the flying speed of the pelicans. We found significant
      directional correlations between the pelican migration flights and wind
      direction. In light of our results, we suggest plasticity of migratory flight
      strategies by pelicans is likely to enhance their ability to cope with the
      effects of ongoing climate change and the alteration of wind regimes. Here, we
      also demonstrate the usefulness and applicability of quantile regression
      techniques to investigate complex ecological processes such as variable effects
      of atmospheric conditions on soaring migration.

PMID- 29065192
TI  - Studies on Vape Shop Density, a Response From the Authors.

PMID- 29065191
TI  - Epstein-Barr virus infection and oral squamous cell carcinoma risk: A meta
      analysis.
AB  - BACKGROUND: The evidence for association between Epstein-Barr virus (EBV)
      infection and risk of oral squamous cell carcinoma (OSCC) is inconsistent in the
      literature. Therefore, this meta-analysis was conducted to clarify this
      association. METHODS: A literature search was conducted in electronic databases
      for English- and Chinese-language publications until March 31, 2017 to include
      eligible case-control studies. The pooled odds ratio (OR) and 95% confidence
      interval (95% CI) were estimated to determine the association between EBV
      infection and OSCC risk using a fixed- or random-effects model based on
      heterogeneity. Publication bias was assessed using funnel plot analysis. RESULTS:
      A total of 13 case-control studies with 686 OSCC patients and 433 controls were
      included based on predetermined inclusion and exclusion criteria. The pooled OR
      with 95% CI between EBV infection and OSCC risk was 5.03 (1.80-14.01) with
      significant heterogeneity observed (I2 = 87%). The subgroup analysis indicates
      that the year of publication, study location, economic level, sample size, tissue
      type, detection method and marker, control type, and language might explain
      potential sources of heterogeneity. Publication bias was not observed, and
      sensitivity analysis showed stable results. CONCLUSIONS: The results of the
      current meta-analysis suggest that EBV infection is statistically associated with
      increased risk of OSCC. However, additional high-quality studies with larger
      sample sizes are needed to further confirm the relationship between EBV and OSCC.

PMID- 29065190
TI  - Discovery and pharmacological characterization of a new class of prolyl-tRNA
      synthetase inhibitor for anti-fibrosis therapy.
AB  - Scleroderma has clinical characteristics including skin and other tissue
      fibrosis, but there is an unmet need for anti-fibrotic therapy. Halofuginone (HF)
      is a well-known anti-fibrosis agent in preclinical and clinical studies which
      exerts its effect via inhibition of TGF-beta/Smad3 signaling pathway. Recently,
      prolyl-tRNA synthetase (PRS) was elucidated as a target protein for HF that binds
      to the proline binding site of the catalytic domain of PRS. Here, we
      characterized a new class of PRS inhibitor (T-3833261) that is carefully designed
      in a way that binds to the ATP site of the catalytic domain and does not disrupt
      binding of proline. The anti-fibrotic activity and the mechanism of action for T
      3833261 on TGF-beta-induced fibrotic assay were compared with those of HF in
      primary human skin fibroblast. We evaluated in vivo effect of topical application
      of T-3833261 and HF on TGF-beta-induced fibrotic genes expression in mice. We
      found that T-3833261 suppressed TGF-beta-induced alpha-smooth muscle actin (alpha
      SMA) and type I collagen alpha1 (COL1A1) expression through the Smad3 axis in a
      similar fashion to HF. In vivo topical application of T-3833261 reduced the
      increase of fibrotic genes expression such as alpha-Sma, Col1a1 and Col1a2 by TGF
      beta intradermal injection to the ear of a mouse. We revealed that T-3833261 is
      more effective than HF under the conditions of high proline concentration, as
      reported in fibrotic tissues. These results suggest the potential of ATP
      competitive PRS inhibitors for the treatment of fibrotic diseases such as
      scleroderma.

PMID- 29065189
TI  - Establishment of a novel hepatocyte model that expresses four cytochrome P450
      genes stably via mammalian-derived artificial chromosome for pharmacokinetics and
      toxicity studies.
AB  - The utility of HepG2 cells to assess drug metabolism and toxicity induced by
      chemical compounds is hampered by their low cytochrome P450 (CYP) activities. To
      overcome this limitation, we established HepG2 cell lines expressing major CYP
      enzymes involved in drug metabolism (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and CYP
      oxidoreductase (POR) using the mammalian-derived artificial chromosome vector.
      Transchromosomic HepG2 (TC-HepG2) cells expressing four CYPs and POR were used to
      determine time- and concentration-dependent inhibition and toxicity of several
      compounds by luminescence detection of CYP-specific substrates and cell viability
      assays. Gene expression levels of all four CYPs and POR, as well as the CYP
      activities, were higher in TC-HepG2 clones than in parental HepG2 cells.
      Additionally, the activity levels of all CYPs were reduced in a concentration
      dependent manner by specific CYP inhibitors. Furthermore, preincubation of TC
      HepG2 cells with CYP inhibitors known as time-dependent inhibitors (TDI) prior to
      the addition of CYP-specific substrates determined that CYP inhibition was
      enhanced in the TDI group than in the non-TDI group. Finally, the IC50 of
      bioactivable compound aflatoxin B1 was lower in TC-HepG2 cells than in HepG2
      cells. In conclusion, the TC-HepG2 cells characterized in the current study are a
      highly versatile model to evaluate drug-drug interactions and hepatotoxicity in
      initial screening of candidate drug compounds, which require a high degree of
      processing capacity and reliability.

PMID- 29065193
TI  - The Acute Effects of a Dopamine D3 Receptor Preferring Agonist on Motivation for
      Cigarettes in Dependent and Occasional Cigarette Smokers.
AB  - Background: Dopaminergic functioning is thought to play critical roles in both
      motivation and addiction. There is preliminary evidence that dopamine agonists
      reduce the motivation for cigarettes in smokers. However, the effects of
      pramipexole, a dopamine D3 receptor preferring agonist, have not been
      investigated. The aim of this study was to examine the effects of an acute dose
      of pramipexole on the motivation to earn cigarettes and nondrug rewards. Methods:
      Twenty dependent and 20 occasional smokers received 0.5 mg pramipexole using a
      double-blind, placebo-controlled crossover design. Motivation for cigarettes and
      consummatory nondrug rewards was measured using the DReaM-Choice task, in which
      participants earned, and later "consumed," cigarettes, music, and chocolate.
      Demand for cigarettes was measured using the Cigarette Purchase Task (CPT). Self
      reported craving, withdrawal, and drug effects were also recorded. Results:
      Dependent smokers chose (p < .001) and button-pressed for (p < .001) cigarettes
      more, and chose chocolate less (p < .001), than occasional smokers. Pramipexole
      did not affect the number of choices for or amount of button-pressing for any
      reward including cigarettes, which was supported by a Bayesian analysis. The
      dependent smokers had greater demand for cigarettes than occasional smokers
      across all CPT outcomes (ps < .021), apart from elasticity. Pramipexole did not
      affect demand for cigarettes, and this was supported by Bayesian analyses.
      Pramipexole produced greater subjective "feel drug" and "dislike drug" effects
      than placebo. Conclusions: Dependent and occasional cigarette smokers differed in
      their motivation for cigarettes but not for the nondrug rewards. Pramipexole did
      not acutely alter motivation for cigarettes. These findings question the role of
      dopamine D3 receptors in cigarette-seeking behavior in dependent and occasional
      smokers. Implications: This study adds to the growing literature about cigarette
      versus nondrug reward processing in nicotine dependence and the role of dopamine
      in cigarette-seeking behavior. Our results suggest nicotine dependence is
      associated with a hypersensitivity to cigarette rewards but not a hyposensitivity
      to nondrug rewards. Furthermore, our results question the importance of dopamine
      D3 receptors in motivational processing of cigarettes in occasional and dependent
      smokers.

PMID- 29065194
TI  - Nicotine-Induced Neuroprotection against Cognitive Dysfunction after Partial
      Hepatectomy Involves Activation of BDNF/TrkB Signaling Pathway and Inhibition of
      NF-kappaB Signaling Pathway in Aged Rats.
AB  - Introduction: The main purpose of this study was to investigate the effects and
      possible mechanisms of nicotine pre-treatment on postoperative cognitive
      dysfunction (POCD) in aged rats. Methods: Nicotine (0.5 mg/kg) was given i.p.
      immediately after anesthesia induction. After the Morris water maze test was used
      to evaluate the rats' spatial learning and memory, serum and hippocampal tissues
      were harvested 1 and 3 days after intervention. Inflammatory cytokines in the
      serum were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). Brain-derived
      neurotrophic factor (BDNF), p-TrkB, neuroinflammation cytokines, NF-kappaB p65,
      and cleaved caspase-3 were measured by western blotting; neuronal apoptosis in
      the hippocampal CA1 region was also evaluated by TUNEL staining. Results: We
      found that nicotine markedly attenuated the POCD and reduced the elevated levels
      of inflammatory cytokines in the serum, including IL-1beta and high mobility
      group box-1 (HMGB1), on postoperative day 1. Additionally, nicotine suppressed
      the surgery-induced release of IL-1beta, TNF-alpha, HMGB1, and NF-kappaB p65 in
      the hippocampus on postoperative day 1 and day 3. In addition, operated rats
      displayed lower BDNF and p-TrkB in the hippocampus on postoperative day 1,
      returning to baseline by postoperative day 3. However, nicotine pre-treatment
      clearly reversed the surgical stress-induced decrease in both BDNF and p-TrkB
      expression in the hippocampus. Furthermore, nicotine pre-treatment significantly
      alleviated the surgery-induced increase in the neuronal apoptosis in the
      hippocampus on postoperative day 1 and day 3. Conclusions: Our results showed
      that nicotine-induced neuroprotection against POCD may involve activation of the
      BDNF/TrkB signaling pathway and inhibition of the NF-kappaB signaling pathway.
      Implications: Nicotine has long been considered a potent therapeutic agent for
      neuroprotection. This study reported the positive effect of nicotine treatment on
      cognitive dysfunction after partial hepatectomy in aged rats. Furthermore, the
      underlying mechanism may involve activation of the BDNF/TrkB signaling pathway
      and inhibition of the NF-kappaB signaling pathway in the hippocampus.

PMID- 29065195
TI  - Movie Language Orientation, Gender, Movie Smoking Exposure, and Smoking
      Susceptibility among Youth in Mexico.
AB  - Introduction: As a result of globalization, youth in Mexico may be exposed to US
      culture remotely. This remote intercultural contact may influence their movie
      language orientation and cigarette smoking. To examine how intercultural contact
      with U.S. culture influences the smoking behaviors of youth in Mexico, this study
      investigated the influence of English- and Spanish-language movie orientation on
      movie smoking exposure through US- and Mexico-produced movies. It also examined
      whether youth movie smoking exposure was associated with higher positive smoking
      related expectancies and greater intentions to smoke cigarettes. Methods:
      Participants were 7524 adolescent never smokers in Mexico (51% female, Mage =
      12.39 years) who completed a school-based survey on movie language orientation,
      movie exposure (from which exposure to tobacco portrayals was estimated), smoking
      related expectancies, and smoking susceptibility. Results: Path and mediation
      analyses indicated that English-language movie orientation was associated with
      greater movie smoking exposure, leading to more positive smoking-related
      expectancies and greater youth smoking susceptibility. Conclusion: Consistent
      with research on the influence of US culture on the smoking of Mexican-heritage
      youth in the United States, findings suggest that orientation toward English
      language movies may put youth in Mexico at risk for smoking initiation. Findings
      extend existing research on intercultural contact and cigarette smoking with
      Hispanic youth in the United States to youth in Mexico. Implications for future
      research are discussed. Implications: This study is one of the first to
      investigate the influence of remote intercultural contact with US culture on
      Mexican youth's smoking-related expectancies and susceptibility. This study
      investigated pathways by which youth's movie language orientation (English vs.
      Spanish) exposed them to movie smoking through US- and Mexico-produced movies,
      thereby influencing their smoking-related cognitions. Findings provide initial
      empirical evidence of a significant association between US remote intercultural
      contact and smoking among youth in Mexico. An important next step is to
      investigate how this process unfolds longitudinally and to investigate additional
      ways youth may engage with US culture to affect their smoking behaviors.

PMID- 29065196
TI  - Compensatory Puffing With Lower Nicotine Concentration E-liquids Increases
      Carbonyl Exposure in E-cigarette Aerosols.
AB  - Introduction: Article 20 of the European Tobacco Products Directive (EU-TPD)
      specifies that e-liquids should not contain nicotine in excess of 20 mg/mL, thus
      many vapers may be compelled to switch to lower concentrations and in so doing,
      may engage in more intensive puffing. This study aimed to establish whether more
      intensive puffing produces higher levels of carbonyl compounds in e-cigarette
      aerosols. Methods: Using the HPLC-UV diode array method, four carbonyl compounds
      (formaldehyde, acetaldehyde, acetone, and acrolein) were measured in liquids and
      aerosols from nicotine solutions of 24 and 6 mg/mL. Aerosols were generated using
      a smoking machine configured to replicate puffing topography data previously
      obtained from 12 experienced e-cigarette users. Results: Carbonyl levels in
      aerosols from the puffing regimen of 6 mg/mL were significantly higher (p < .05
      using independent samples t tests) compared with those of 24 mg/mL nicotine. For
      the 6 and 24 mg/mL nicotine aerosols respectively, means +/- SD for formaldehyde
      levels were 3.41 +/- 0.94, and 1.49 +/- 0.30 ug per hour (ug/h) of e-cigarette
      use. Means +/- SD for acetaldehyde levels were 2.17 +/- 0.36 and 1.04 +/- 0.13
      ug/h. Means +/- SD for acetone levels were 0.73 +/- 0.20 and 0.28 +/- 0.14 ug/h.
      Acrolein was not detected. Conclusions: Higher levels of carbonyls associated
      with more intensive puffing suggest that vapers switching to lower nicotine
      concentrations (either due to the EU-TPD implementation or personal choice), may
      increase their exposure to these compounds. Based on real human puffing
      topography data, this study suggests that limiting nicotine concentrations to 20
      mg/mL may not result in the desired harm minimalization effect. Implications:
      More intensive puffing regimens associated with the use of low nicotine
      concentration e-liquids can lead to higher levels of carbonyl generation in the
      aerosol. Although in need of replication in a larger sample outside a laboratory,
      this study provides pragmatic empirical data on the potential risks of
      compensatory puffing behaviors in vapers, and can help to inform future
      regulatory decisions on nicotine e-liquid concentrations. The cap on nicotine
      concentration at 20 mg/mL set by the EU-TPD may therefore have the unintended
      consequence of encouraging use of lower nicotine concentration e-liquid, in turn
      increasing exposure to carbonyl compounds through compensatory puffing.

PMID- 29065198
TI  - Disgust but not Health Anxiety Graphic Warning Labels Reduce Motivated Attention
      in Smokers: A Study of P300 and Late Positive Potential Responses.
AB  - Background: Graphic health warning labels (GHWLs) on tobacco products attempt to
      leverage avoidance-promoting emotions, such as anxiety and disgust, to encourage
      cessation. Prior studies have relied on self-report or attentional metrics that
      may not accurately illuminate GHWLs' ability to motivate change. This report
      evaluates the impact of disgust- and anxiety-based GHWLs on electroencephalograph
      (EEG) measures of motivated attention among two groups of smokers-those that
      report higher versus lower cigarette dependence. We hypothesized that both
      anxiety and disgust GHWLs would reduce appetitive attention, as indexed by
      lowered P300 (P3) and late positive potential (LPP) activations. Methods: Sixty
      one smokers provided demographic and smoking history before completing an oddball
      paradigm consisting of three counterbalanced stimuli blocks. Each block (100
      trials) contained a neutral, GHWL-anxiety, or GHWL-disgust frequent image and a
      smoking cue as the oddball image (20%). Oddball trials for each block were
      averaged, P3 and LPP were identified at midline electrode positions (Fz, Cz, and
      Pz), and mean amplitude was analyzed. Results: Separate mixed-model ANOVAs of P3
      and LPP reactivity revealed disgust-focused GHWLs reduced motivated attentional
      processing. Conversely, the anxiety-focused GHWL appeared to increase the
      salience of the smoking cue (Fz only). Less-dependent smokers showed lower P3
      reactivity than those with higher dependence at Fz, but greater P3 reactivity at
      Cz and Pz. Conclusion: These results extend prior work in demonstrating that
      disgust, but not anxiety-based GHWLs, may reduce EEG-assessed motivated attention
      to smoking cues. Disgust may thus represent a more fruitful target for public
      health cessation efforts. Implications: Most GHWL evaluations have focused on
      fear (or anxiety) elicitation rather than disgust, an emotion that may have a
      unique link to smoking, having evolved specifically to facilitate the avoidance
      of contaminants via oral incorporation. Analyses of P300 and LPP responses to
      GHWLs suggest that disgust-focused images interfere with the EEG-indexed
      attentional processing of smoking cues and do so better than health anxiety
      focused messages. However, interaction effects at different electrode sites
      indicated that GHWLs have complex effects in more versus less-dependent smokers
      and that an understanding of how smoking cues and anti-smoking imagery become
      associated over time is needed to identify relevant targets for public health
      efforts.

PMID- 29065197
TI  - Effects of Filter Ventilation on Behavioral Economic Demand for Cigarettes: A
      Preliminary Investigation.
AB  - Introduction: The majority of cigarettes sold in the United States and abroad
      feature filter ventilation holes designed to dilute mainstream smoke. Although
      initially intended to produce a safer cigarette, data instead suggest that filter
      ventilation increases total harm from smoking. In the present study, we examined
      the effects of blocking ventilation holes on behavioral economic demand for
      cigarettes (i.e., consumption as a function of price). Methods: In a within
      subjects design, regular smokers (N = 15) of ventilated cigarettes sampled vent
      blocked cigarettes for 3 days. Subsequently, they completed three sessions in
      which they used an experimental income to purchase vent-blocked and/or control
      cigarettes across a range of prices. Participants also completed the Drug
      Effects/Liking Scale. Results: In sessions in which only one cigarette type was
      available, demand measures were undifferentiated between cigarette types.
      However, in sessions in which both cigarettes were available at equivalent
      prices, significantly greater preference for ventilated control cigarettes
      emerged in demand measures. Regardless of session type, participants also rated
      vent-blocked cigarettes more poorly in the Drug Effects/Liking Scale (more bad
      effects, fewer good effects, and less liking, desire, and less likely to use
      again). Conclusions: Removing filter ventilation reduced cigarette abuse
      liability, as measured by behavioral economic demand and the Drug Effects/Liking
      Scale. However, reduced demand was only apparent when both cigarette types were
      concurrently available. This selective effect suggests that regulatory action
      banning filter ventilation would only reduce cigarette consumption when effective
      substitutes for vent-blocked cigarettes are available. Implications: This
      preliminary study indicates that regulatory action designed to ban or restrict
      cigarette filter ventilation may decrease cigarette abuse liability as measured
      by both behavioral economic demand and self-report measures. However, effects of
      removing filter ventilation on demand measures appear to depend on concurrent
      availability of alternative, preferred cigarette types.

PMID- 29065199
TI  - Prevalence and Correlates of Smoking Among People Living With HIV in South
      Africa.
AB  - Introduction: Smoking likely exacerbates comorbidities which people living with
      HIV (PLWH) are predisposed. We assessed prevalence and correlates of smoking
      among PLWH in South Africa, which has 7 million PLWH but inadequate reporting of
      smoking. Methods: A cross-sectional survey was conducted among randomly selected
      adults with HIV infection in Klerksdorp, South Africa. Current smoking was
      assessed by questionnaire, exhaled carbon monoxide (eCO), and urine cotinine.
      Results: Of 1210 enrolled adults, 753 (62%) were women. In total, 409 (34%) self
      reported ever smoking: 301 (74%) were current and 108 (26%) were former smokers.
      Using eCO and urine cotinine tests, 239 (52%) men and 100 (13%) women were
      defined as current smokers. Nearly all smokers (99%) were receiving ART, and had
      a median (IQR) CD4 count of 333 cells/MUL (181-534), viral load of 31 IU/mL (25
      4750), and BMI of 21 kg/m2 (19-24). Adjusted analysis among men showed higher
      odds of smoking with marijuana use (OR = 7.5, 95% CI = 4.1 to 14.6). Among women,
      304 (43%) reported using snuff, compared to only 11 (3%) of men, and snuff use
      was inversely associated with smoking (OR = 0.1; 95% CI = 0.05 to 0.2). A subset
      of participants (n = 336) was asked about alcohol use, which was positively
      associated with smoking for men (OR = 8.1, 95% CI = 2.8 to 25.9) and women (OR =
      8.5, 95% CI = 2.9 to 26.8). Conclusion: Smoking prevalence among PLWH in South
      Africa is alarmingly high. Prevention and cessation strategies that consider
      marijuana and alcohol use are needed. Implications: As long-term HIV care
      continues to improve, more people living with HIV (PLWH) will die of diseases,
      including tuberculosis, for which smoking plays an important causal role. The
      prevalence of smoking is markedly higher among PLWH in high-resource settings,
      but data for Africa and other low-resource settings that shoulder the brunt of
      the HIV epidemic has previously not been well documented. We report an alarmingly
      high prevalence of smoking among PLWH in South Africa, particularly among men,
      and a strong association between current smoking and use of other substances.

PMID- 29065201
TI  - Objectivity and Evidence in the 2016 Surgeon General's Report on E-Cigarettes.

PMID- 29065203
TI  - Predictors of Postpartum Return to Smoking: A Systematic Review.
AB  - Background: Finding effective ways to help pregnant women quit smoking and remain
      abstinent is a major public health issue. Approximately half of UK women who
      smoke attempt cessation after conception; unfortunately, up to 75% return to
      smoking within 12 months postpartum. Interventions for preventing postpartum
      return to smoking (PPRS) have not been found to be effective. It is important to
      identify factors associated with PPRS, to inform development of alternative
      interventions. Aim: Identify by systematic review factors associated with PPRS.
      Methods: Systematic searches of electronic databases (MEDLINE, EMBASE, PsychINFO,
      CINAHL), trials registers, and conference proceedings were conducted to November
      2016. Studies statistically examining factors associated with PPRS were included.
      Modified versions of the Newcastle Ottawa Quality Assessment Scale were used to
      assess studies' quality and a narrative synthesis focused on those judged of high
      quality. Results: Thirty-nine studies (12 trials, 27 observational studies) were
      included. Thirty-one (79.5%) studies were high-quality. Among these, the most
      common significant predictors of PPRS were being less well educated, younger,
      multiparous, living with a partner or household member who smoked, experiencing
      higher stress, depression or anxiety, not breastfeeding, intending to quit only
      for pregnancy and low confidence to remain abstinent postpartum. Conclusions: Of
      the factors found to be associated with PPRS, intending to quit smoking only for
      the duration of pregnancy, partner/household member smoking and confidence to
      remain abstinent are those most likely to have a direct, causal impact on smoking
      behavior after childbirth, and need to be considered when designing interventions
      to prevent PPRS. Implications: This is the first systematic review of factors
      that may facilitate or inhibit PPRS. Considering how having a partner or
      household member who smokes, intending to quit smoking only for pregnancy, having
      self-efficacy to quit long term, breastfeeding and depression exert direct or
      indirect impacts on women's relapse to smoking and how such impacts could
      successfully be manipulated will inform development of new interventions to
      prevent PPRS.

PMID- 29065200
TI  - Basic Science and Public Policy: Informed Regulation for Nicotine and Tobacco
      Products.
AB  - Introduction: Scientific discoveries over the past few decades have provided
      significant insight into the abuse liability and negative health consequences
      associated with tobacco and nicotine-containing products. While many of these
      advances have led to the development of policies and laws that regulate access to
      and formulations of these products, further research is critical to guide future
      regulatory efforts, especially as novel nicotine-containing products are
      introduced and selectively marketed to vulnerable populations. Discussion: In
      this narrative review, we provide an overview of the scientific findings that
      have impacted regulatory policy and discuss considerations for further
      translation of science into policy decisions. We propose that open, bidirectional
      communication between scientists and policy makers is essential to develop
      transformative preventive- and intervention-focused policies and programs to
      reduce appeal, abuse liability, and toxicity of the products. Conclusions:
      Through these types of interactions, collaborative efforts to inform and modify
      policy have the potential to significantly decrease the use of tobacco and
      alternative nicotine products and thus enhance health outcomes for individuals.
      Implications: This work addresses current topics in the nicotine and tobacco
      research field to emphasize the importance of basic science research and provide
      examples of how it can be utilized to inform public policy. In addition to
      relaying current thoughts on the topic from experts in the field, the article
      encourages continued efforts and communication between basic scientists and
      policy officials.

PMID- 29065202
TI  - What Do Smokers Want in A Smartphone-Based Cessation Application?
AB  - Background: Fueled by rapid technological advances over the past decade, there is
      growing interest in the use of smartphones to aid in smoking cessation. Hundreds
      of applications have been developed for this purpose, but little is known about
      how these applications are accessed and used by smokers or what features smokers
      believe would be most useful. Purpose: The present study sought to understand the
      prevalence of smartphone ownership and patterns of use among smokers as well as
      the perceived utility of various smartphone application features for smoking
      cessation that are currently in development or already available. Methods: Daily
      cigarette smokers (n = 224) reported on smartphone ownership, their patterns of
      smartphone usage, and perceived utility of features. Features were ranked
      according to perceived utility and differences in both perceived utility and
      general smartphone use patterns were examined as a function of demographic and
      smoking-related variables. Results: Most smokers (80.4%) own a smartphone, but
      experience with smoking cessation applications is extremely rare (6.1%).
      Ownership and patterns of usage differed as a function of demographic and smoking
      related variables. Overall, gain-framed features were rated as most useful, while
      loss-framed and interpersonal features were rated as least useful. Conclusions:
      Mobile health interventions have the potential to reach a large number of smokers
      but are currently underutilized. Additional effort is needed to ensure parity in
      treatment access. Gain-framed messages may be especially useful for engaging
      smokers, even if other features ultimately drive treatment effects. Implications:
      This study describes patterns of smartphone usage among smokers and identifies
      the smartphone application features smokers believe would be most useful during a
      quit attempt. Findings indicate which subgroups of smokers are most likely to be
      reached with mobile health interventions and suggests that inclusion of specific
      features may be helpful for engaging smokers in the smoking cessation process.

PMID- 29065204
TI  - The Role of Nicotine Dependence in E-Cigarettes' Potential for Smoking Reduction.
AB  - Introduction: E-cigarettes (Electronic Nicotine Delivery Systems, or ENDS) are an
      increasingly popular tobacco product among youth. Some evidence suggests that e
      cigarettes may be effective for harm reduction and smoking cessation, although
      these claims remain controversial. Little is known about how nicotine dependence
      may contribute to e-cigarettes' effectiveness in reducing or quitting
      conventional smoking. Methods: A cohort of young adults were surveyed over 4
      years (approximately ages 19-23). Varying-coefficient models (VCMs) were used to
      examine the relationship between e-cigarette use and conventional smoking
      frequency, and how this relationship varies across users with different nicotine
      dependence levels. Results: Lifetime, but not recent, e-cigarette use was
      associated with less frequent concurrent smoking of conventional cigarettes among
      those with high levels of nicotine dependence. However, nondependent e-cigarette
      users smoked conventional cigarettes slightly more frequently than those who had
      never used e-cigarettes. Nearly half of ever e-cigarette users reported using
      them to quit smoking at the last measurement wave. For those who used e
      cigarettes in a cessation attempt, the frequency of e-cigarette use was not
      associated with reductions in future conventional smoking frequency. Conclusions:
      These findings offer possible support that e-cigarettes may act as a smoking
      reduction method among highly nicotine-dependent young adult cigarette smokers.
      However, the opposite was found in non-dependent smokers, suggesting that e
      cigarette use should be discouraged among novice tobacco users. Additionally,
      although a substantial proportion of young adults used e-cigarettes to help them
      quit smoking, these self-initiated quit attempts with e-cigarettes were not
      associated with future smoking reduction or cessation. Implications: This study
      offers potential support for e-cigarettes as a smoking reduction tool among
      highly nicotine-dependent young adult conventional smokers, although the extent
      and nature of this remains unclear. The use of e-cigarettes as a quit aid was not
      associated with reductions in conventional smoking, consistent with most other
      quit aids in this sample except for nicotine replacement therapy, which was only
      effective for the most dependent smokers. Notably, these findings highlight the
      necessity of accounting for smokers' nicotine dependence levels when examining
      tobacco use patterns.

PMID- 29065205
TI  - Content Analysis of US News Stories About E-Cigarettes in 2015.
AB  - Background: Coverage of e-cigarettes in the news media may shape public
      perceptions about them but little is known about such news content. This content
      analysis characterized discussion of e-cigarettes in leading print and online US
      news sources in 2015. Methods: We searched Access World News and Factiva
      databases for e-cigarette-related news articles appearing in the top 30
      circulating newspapers, 4 newswires, and 4 online news sources in the United
      States in 2015 (n = 295). Coders identified the presence of various e-cigarette
      topics (e.g. regulation), and benefit and risk statements. Results: Nearly half
      of articles (45.1%) focused primarily on e-cigarette policy/regulatory issues,
      although e-cigarette prevalence (21.0%) and health effects (21.7%) were common
      main topics. Concerns about youth were frequently mentioned, including the rise
      in youth e-cigarette use (45.4%), gateway to smoking potential (33.9%) and appeal
      of flavors (22.4%). Youth e-cigarette prevalence was more frequently mentioned
      than adult prevalence in articles discussing FDA regulation (61% vs. 13.5%,
      respectively). News articles more frequently discussed potential e-cigarette
      risks or concerns (80%) than benefits (45.4%), such as smoking harm-reduction.
      Quoted physicians, researchers, and government representatives were more likely
      to refer to e-cigarette risks than benefits. Conclusions: In 2015, rising rates
      of e-cigarette use among youth and policy strategies to address e-cigarettes
      dominated US e-cigarette news stories, leading up to their FDA regulation in
      2016. Statements about e-cigarettes' potential risks were frequently attributed
      to trusted sources such as physicians, and outnumbered claims about their harm
      reduction benefits. Such coverage may impact e-cigarette risk perceptions, use
      intentions and policy support. Implications: In the year leading up to the FDA's
      Deeming Rule, concerns about youth use or potential use were frequently discussed
      in e-cigarette news. News articles more frequently discussed potential e
      cigarette risks/concerns compared to potential harm-reduction benefits relative
      to tobacco cigarettes. While such coverage may inform the public about potential
      e-cigarette risks, they may also contribute to increasing perceptions that e
      cigarettes are as harmful as tobacco cigarettes. E-cigarette risk and benefit
      statements were most frequently made by or attributed to researchers and
      physicians in articles, which is significant given that they may be particularly
      trusted sources of e-cigarette risk information.

PMID- 29065206
TI  - The Regulatory Environment and Cost of Electronic Cigarettes in Italy, 2014-2015,
      Influenced their Use for Quitting.

PMID- 29065208
TI  - Advice From Former-Smoking E-Cigarette Users to Current Smokers on How to Use E
      Cigarettes as Part of an Attempt to Quit Smoking.
AB  - Introduction: Substitution of e-cigarettes for tobacco smoking has the potential
      to prevent almost all the harm caused by smoking. Identifying strategies that may
      increase smokers' capability, opportunity and motivation to use e-cigarettes in
      place of tobacco cigarettes is vital. Former smokers who have successfully used e
      cigarettes to quit smoking may be especially well qualified to increase current
      smokers' interest in switching and ability to switch to e-cigarettes. Methods: A
      multi-national, self-selected sample of 4192 former smokers who quit smoking by
      using e-cigarettes were asked, via an online survey, the advice they would offer
      to smokers who are considering using e-cigarettes to support an attempt to quit
      smoking. Results: Thematic analysis of participants' qualitative responses
      identified four emergent themes: (1) Find a combination of vaping device, flavors
      of e-liquid and nicotine strength that "works for you"; (2) Continuing to smoke
      for a while after starting to vape is OK; (3) Failure to quit smoking with the
      use of approved smoking cessation aids before success with e-cigarettes is
      common; and (4) Awareness of improved health and hygiene since switching to
      vaping. Conclusions: Experienced vapers who used to smoke appear eager to give
      smokers advice and practical information about vaping that may assist attempts to
      switch from smoking to vaping. Encouraging cigarette smokers to interact with
      experienced vapers in places where vapers themselves once received advice and now
      give advice about vaping-vape shops and online discussion fora-may have
      significant potential to help more smokers to switch to e-cigarette use.
      Implications: This study describes the advice that former-smokers who used e
      cigarettes to quit smoking would offer to smokers who are considering using an e
      cigarette to support an attempt to quit smoking. Vapers advised smokers to find
      the right combination of device, flavors and nicotine strength, continue to smoke
      and vape for a while if they wished, not be deterred by past failed attempts to
      quit smoking, and expect health to improve after they have switched to vaping.
      Encouraging smokers to interact with vaping peers in vape shops and in online
      vaping-dedicated discussion fora may help significantly more smokers switch to
      vaping.

PMID- 29065210
TI  - Toward an Equitable Society for Every Generation.

PMID- 29065213
TI  - Hitting Reset, Finding Common Ground, and Strengthening Care Delivery for Older
      Adults.

PMID- 29065212
TI  - Evidence-Based Practice Guideline: Fall Prevention for Older Adults.
AB  - Falls are a major cause of injury and death annually for millions of individuals
      65 and older. Older adults are at risk for falls for a variety of reasons
      regardless of where they live. Falls are defined as any sudden drop from one
      surface to a lower surface. The purpose of this fall prevention evidence-based
      practice guideline is to describe strategies that can identify individuals at
      risk for falls. A 10-step protocol including screening for falls, comprehensive
      fall assessment, gait and balance screening when necessary, and an individualized
      fall intervention program addressing specific fall risks is presented.
      Reassessing fall risk and fall prevention programs will ensure a proactive
      approach to reducing falls in the aging population. [Journal of Gerontological
      Nursing, 43(11), 15-21.].

PMID- 29065214
TI  - Changing contributions of stochastic and deterministic processes in community
      assembly over a successional gradient.
AB  - Successional dynamics in plant community assembly may result from both
      deterministic and stochastic ecological processes. The relative importance of
      different ecological processes is expected to vary over the successional
      sequence, between different plant functional groups, and with the disturbance
      levels and land-use management regimes of the successional systems. We evaluate
      the relative importance of stochastic and deterministic processes in bryophyte
      and vascular plant community assembly after fire in grazed and ungrazed
      anthropogenic coastal heathlands in Northern Europe. A replicated series of post
      fire successions (n = 12) were initiated under grazed and ungrazed conditions,
      and vegetation data were recorded in permanent plots over 13 years. We used
      redundancy analysis (RDA) to test for deterministic successional patterns in
      species composition repeated across the replicate successional series and
      analyses of co-occurrence to evaluate to what extent species respond
      synchronously along the successional gradient. Change in species co-occurrences
      over succession indicates stochastic successional dynamics at the species level
      (i.e., species equivalence), whereas constancy in co-occurrence indicates
      deterministic dynamics (successional niche differentiation). The RDA shows high
      and deterministic vascular plant community compositional change, especially early
      in succession. Co-occurrence analyses indicate stochastic species-level dynamics
      the first two years, which then give way to more deterministic replacements.
      Grazed and ungrazed successions are similar, but the early stage stochasticity is
      higher in ungrazed areas. Bryophyte communities in ungrazed successions resemble
      vascular plant communities. In contrast, bryophytes in grazed successions showed
      consistently high stochasticity and low determinism in both community composition
      and species co-occurrence. In conclusion, stochastic and individualistic species
      responses early in succession give way to more niche-driven dynamics in later
      successional stages. Grazing reduces predictability in both successional trends
      and species-level dynamics, especially in plant functional groups that are not
      well adapted to disturbance.

PMID- 29065207
TI  - Cerebellar Gray Matter Reductions Associate With Decreased Functional
      Connectivity in Nicotine-Dependent Individuals.
AB  - Introduction: Nicotine dependence (ND) is a chronic, relapsing mental disorder
      characterized by compulsive cigarette seeking and smoking. Although the
      cerebellum plays an increasingly implicated role in ND, the exact cerebellar
      alterations in ND remain unclear. Identifying the localization of these
      cerebellar abnormalities in ND may help to further understand the role of the
      cerebellum in ND. Thus, we investigated the structural and functional alterations
      in the cerebellum in a large sample of smokers using the spatially unbiased
      infratentorial template (SUIT). Methods: High-resolution structural magnetic
      resonance imaging (MRI) data were acquired from 85 smokers and 41 nonsmokers. We
      applied voxel-based morphometry (VBM) and the SUIT cerebellar atlas to compare
      the cerebellar gray matter (GM) volume between smokers and nonsmokers. Using
      resting-state functional MRI data, we also performed seed-based functional
      connectivity (FC) analysis to examine the functional correlates of the GM volume
      changes. Results: Both VBM and lobular analyses revealed smaller GM volume in the
      bilateral Crus I in smokers. The GM volume of the left Crus I was inversely
      correlated with the severity of nicotine dependence as assessed by Fagerstrom
      Test for Nicotine Dependence (r = -.268, p = .013). We also found reduced FC
      between the bilateral Crus I and brain regions involved in the default mode
      network and motor system, as well as the frontal and temporal cortex in smokers.
      Conclusions: Our results indicate that decreased cerebellar GM volume and
      corticocerebellar FC are associated with ND, and these may underlie the core ND
      phenotypes, including automatized smoking behavior, cognitive, and emotional
      deficits. Implications: As smoking remains a worldwide public health problem,
      identifying the related neural alterations may help to understand the
      pathophysiology of ND. Based on previous findings in the cerebellum, we
      investigated the localization of the GM differences and related FC changes in ND
      subjects. Our findings highlight altered corticocerebellar circuits in ND,
      suggesting an association between the cerebellum and the phenotypes of ND.

PMID- 29065215
TI  - On the catabolism of amino acids in the yeast Dekkera bruxellensis and the
      implications for industrial fermentation processes.
AB  - In the last years several reports have reported the capacity of the yeast Dekkera
      (Brettanomyces) bruxellensis to survive and adapt to the industrial process of
      alcoholic fermentation. Much of this feature seems to relate to the ability to
      assimilate limiting sources of nutrients, or somehow some that are inaccessible
      to Saccharomyces cerevisiae, in particular the sources of nitrogen. Among them,
      amino acids (AA) are relevant in terms of beverage musts, and could also be
      important for bioethanol. In view of the limited knowledge on the control of AA,
      the present work combines physiological and genetic studies to understand how it
      operates in D. bruxellensis in response to oxygen availibility. The results
      allowed separation of the AA in three groups of preferentiality and showed that
      glutamine is the preferred AA irrespective of the presence of oxygen. Glutamate
      and aspartate were also preferred AA in anaerobiosis, as indicated by the
      physiological data. Gene expression experiments showed that, apart from the
      conventional nitrogen catabolic repression mechanism that is operating in
      aerobiosis, there seems to be an oxygen-independent mechanism acting to
      overexpress key genes like GAP1, GDH1, GDH2 and GLT1 to ensure adequate anaerobic
      growth even in the presence of non-preferential nitrogen source. This could be of
      major importance for the industrial fitness of this yeast species.

PMID- 29065217
TI  - The fission yeast MAPK Spc1 senses perturbations in Cdc25 and Wee1 activities and
      targets Rad24 to restore this balance.
AB  - Mitogen-activated protein kinases (MAPKs) play vital roles in multiple cellular
      processes and represent prominently pursued targets for development of
      therapeutic regimes. The MAPK Spc1 (p38 homologue) is known to be very important
      for both mitotic promotion and delay in Schizosaccharomyces pombe. However, the
      mechanism responsible for mitotic inhibition has remained elusive. Cdc25 (Cdc2
      activator) and Wee1 (Cdc2 inhibtor) are important determinants of mitotic timing
      in all eukaryotes. Our results show that Spc1 can sense the perturbations in the
      balance of Cdc25 and Wee1 activities in S. pombe and that its function as a
      mitotic inhibitor is very important for controlling the same. An Spc1-Srk1-Rad24
      dependent pathway for mitotic inhibition has been reported earlier.Here we report
      the presence of an alternative mechanism wherein Spc1 targets the 14-3-3 protein,
      Rad24, independently of Srk1, leading to relocalization of Cdc25 and mitotic
      inhibition. Our observations suggest that this pathway can serve as a backup
      mechanism for Cdc2 inactivation in the absence of Wee1.

PMID- 29065218
TI  - Renal vectorial transport of berberine mediated by organic cation transporter 2
      (OCT2) and multidrug and toxin extrusion proteins 1 (MATE1) in rats.
AB  - Berberine, a well-known plant alkaloid derived from Rhizoma coptidis, has
      potential applications as a therapeutic drug for diabetic nephropathy. However,
      the transporter-mediated renal transport of berberine remains largely unclear.
      This study aimed to investigate the renal transport mechanism of berberine using
      transfected cells, kidney slices and animal experiments. In Madin-Darby canine
      kidney (MDCK) cells stably expressing rat OCT2 (MDCK-rOCT2) and kidney slices,
      saturable and non-saturable uptake of berberine was observed, and corticosterone
      could inhibit the uptake of berberine, with IC50 values of 0.1 MUm and 147.9 MUm,
      respectively. In double-transfected cells, the cellular accumulation of berberine
      into MDCK-rOCT2 and MDCK-rOCT2-rMATE1 (MDCK cells stably expressing rOCT2 and
      rMATE1) cells was significantly higher than the uptake into MDCK cells.
      Meanwhile, berberine transcellular transport was considerably higher in double
      transfected MDCK-rOCT2-rMATE1 cells than in MDCK and MDCK-rOCT2 cells.
      Corticosterone for MDCK-rMATE1 and MDCK-MDR1 and pyrimethamine for MDCK-rMATE1 at
      high concentrations could inhibit the efflux of berberine. In animal experiments,
      compared with the berberine alone group, the cumulative urinary excretion of
      berberine significantly decreased in the corticosterone or pyrimethamine
      pretreatment groups. In the rat kidney, pyrimethamine increased, and a low dose
      of corticosterone (5 mg/kg) decreased, the berberine concentration. However,
      there was no apparent change in the renal concentration of berberine in rats
      pretreated with corticosterone (10 or 20 mg/kg). Thus, berberine is not only a
      substrate of OCT2 and P-glycoprotein, but is also a substrate of MATE1. Both OCT2
      and MATE1 mediate the renal vectorial transport of berberine.

PMID- 29065216
TI  - Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST-Decreasing HMG-CoA
      Reductase Expression Via AMP-Activated Protein Kinase.
AB  - : GINST, a hydrolyzed ginseng extract, has been reported to have antidiabetic
      effects and to reduce hyperglycemia and hyperlipidemia. Hypercholesterolemia is
      caused by diet or genetic factors and can lead to atherosclerosis and coronary
      heart disease. Thus, the purpose of this study is to determine whether GINST and
      the ginsenoside metabolite, IH-901 (compound K), reduce cholesterol synthesis in
      HepG2 cells and the signal transduction pathways involved. Concentrations of
      cholesterol were measured by using an enzymatic method. Expression levels of
      sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR),
      peroxisome proliferators-activated receptor gamma (PPARgamma), CCAAT/enhancer
      binding proteins alpha (C/EBPalpha), GAPDH, and phosphorylation of AMP-activated
      protein kinase alpha (AMPKalpha), protein kinase B (PKB, also known as Akt), and
      mechanistic target of rapamycin complex 1 (mTORC1) were measured using western
      blot. Total cholesterol concentration decreased after GINST treatment for 24 and
      48 h. Expression of HMGCR decreased more with GINST than with the inhibitors,
      U18666A and atorvastatin, after 48 h in a dose-dependent manner. Phosphorylation
      of AMPKalpha increased 2.5x by GINST after 360 min of treatment, and
      phosphorylation of Akt decreased after 120 and 360 min. We separated compound K
      from GINST extracts flash chromatography. Compound K decreased cholesterol
      synthesis in HepG2 cells at 24 and 48 h. Therefore, we conclude that GINST
      inhibits cholesterol synthesis in HepG2 cells by decreasing HMGCR expression via
      AMPKalpha activation. PRACTICAL APPLICATION: GINST, a hydrolyzed ginseng extract,
      can inhibit cholesterol synthesis in liver cells via activation of AMPKalpha. IH
      901 (compound K), which is the main component with bioactivity in GINST, also has
      anticholesterol effects. Thus, we suggest that GINST can be used to reduce
      hypercholesterolemia.

PMID- 29065219
TI  - Simple Preparation of Thiol-Ene Particles in Glycerol and Surface
      Functionalization by Thiol-Ene Chemistry (TEC) and Surface Chain Transfer Free
      Radical Polymerization (SCT-FRP).
AB  - Thiol-ene (TE)-based polymer particles are traditionally prepared via emulsion
      polymerization in water (using surfactants, stabilizers, and cosolvents). Here, a
      green and simple alternative is presented with excellent control over particle
      size, while avoiding the addition of stabilizers. Glycerol is applied as a
      dispersing medium for the preparation of off-stoichiometric TE microparticles,
      where sizes in the range of 40-400 um are obtained solely by changing the mixing
      speed of the emulsions prior to crosslinking. Control over surface chemistry is
      achieved by surface functionalization of excess thiol groups via photochemical
      thiol-ene chemistry resulting in a functional monolayer. In addition, surface
      chain transfer free radical polymerization is used for the first time to
      introduce a thicker polymer layer on the particle surface. The application
      potential of the system is demonstrated by using functional particles as
      adsorbent for metal ions and as a support for immobilized enzymes.

PMID- 29065220
TI  - Effective Acetylene/Ethylene Separation at Ambient Conditions by a Pigment-Based
      Covalent-Triazine Framework.
AB  - A novel covalent-triazine framework (CTF-PO71) is designed and prepared from an
      organic pigment molecule for high-performance gas separation. The functional
      sites with different electrostatic potentials on the pore surface of CTF-PO71
      demonstrate a strong interaction between C2 H2 and CTF-PO71 to achieve
      preferential adsorption of C2 H2 over C2 H4 , thus enabling effective capture of
      a trace amount of C2 H2 from the gas mixture. This is the first organic porous
      polymer that is capable of separating C2 H2 and C2 H4 . The commercial
      availability and the low cost of the pigment as well as the high stability of the
      resultant framework endow CTF-PO71 with a significant potential for practical
      applications.

PMID- 29065222
TI  - Digital quantitative analysis of mast cell infiltration in interstitial cystitis.
AB  - AIMS: To evaluate the significance of mast cell infiltration in interstitial
      cystitis (IC) by comparison with equally inflamed controls using a digital
      quantification technique. METHODS: Bladder biopsy specimens from 31 patients with
      Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder
      biopsy specimens from 37 patients without IC, including 19 non-specific chronic
      cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal
      bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and
      CD138-immunoreactive cells were quantified using digital image analysis software
      to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and
      lymphoplasmacytic cell densities were counted independently in the entire lamina
      propria and detrusor areas and compared among the four groups. RESULTS: In the
      lamina propria, there were no significant differences in mast cell and
      lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or
      between non-Hunner type IC and normal bladder specimens. In the detrusor, the
      mast cell densities were not significantly different among the four groups. Mast
      cell density was correlated with lymphoplasmacytic cell density, but not with
      clinical parameters. CONCLUSIONS: Mast cell density is not significantly
      different between IC specimens and non-IC control specimens with a similar degree
      of background inflammation. The intensity of mast cell infiltration generally
      correlated with that of lymphoplasmacytic cells. We conclude that mast cell count
      is of no value in the differential diagnosis between IC and other etiologies.

PMID- 29065224
TI  - An On-Surface Reaction Confined within a Porous Molecular Template.
AB  - On-surface reactions based on metal-catalysed Ullmann coupling have been
      successfully employed to synthesise a wide variety of covalently coupled
      structures. Substrate chemistry and topology are both known to effect the
      progression of an on-surface reaction; offering routes to control efficiency and
      selectivity. Here, we detail ultra-high vacuum scanning probe microscopy
      experiments showing that templating a catalytically active surface, via a
      supramolecular template, influences the reaction pathway of an on-surface Ullmann
      type coupling reaction by inhibiting one potential intermediate structure and
      stabilising another.

PMID- 29065223
TI  - Influence of polysaccharide-based edible coatings as carriers of prebiotic fibers
      on quality attributes of ready-to-eat fresh blueberries.
AB  - BACKGROUND: Little information is available regarding the effect of dietary
      fibers added into edible coatings on quality attributes of ready-to-eat fruits.
      The aim of this study was to evaluate the effects of sodium alginate (AL) and
      chitosan (CH) edible coatings enriched with four different dietary fibers (apple
      fiber, orange fiber, inulin and oligofructose) on microbiological, nutritional,
      physico-chemical and sensorial properties of ready-to-eat fresh blueberries
      stored for 18 days at 5  degrees C. RESULTS: The most encouraging results were
      found for CH coatings (with and without fibers) which significantly inhibited the
      growth of mesophilic bacteria and yeasts/molds (reductions up to 1.9 log CFU g-1
      ), reduced decay rate by more than 50%, enhanced antioxidant properties, retained
      fruit firmness, delayed off-odor development and improved overall visual quality
      of blueberries. Oligofructose and orange fiber added to CH coatings enhanced
      antioxidant properties of fruits and allowed higher reductions in yeast/mold
      counts compared to the use of CH alone. CH-based coatings enriched with inulin,
      oligofructose and apple fiber extended sensory shelf life of blueberries by 6
      days. AL coatings (with and without fiber) allowed delaying fungal decay and also
      retaining antioxidant properties but did not improve the microbiological and
      sensory quality of fruits. CONCLUSION: The results proved that fiber-enriched CH
      treatments allowed the maintenance of freshness and the improvement of the
      quality of ready-to-eat blueberries. It might be an interesting option to offer
      consumers a healthy product with prebiotic potential and an extended shelf life.
      (c) 2017 Society of Chemical Industry.

PMID- 29065221
TI  - Berberine attenuates hepatic steatosis and enhances energy expenditure in mice by
      inducing autophagy and fibroblast growth factor 21.
AB  - BACKGROUND AND PURPOSE: Berberine, a compound from rhizome coptidis, is
      traditionally used to treat gastrointestinal infections, such as bacterial
      diarrhoea. Recently, berberine was shown to have hypoglycaemic and hypolipidaemic
      effects. We investigated the mechanisms by which berberine regulates hepatic
      lipid metabolism and energy expenditure in mice. EXPERIMENTAL APPROACH: Liver
      specific SIRT1 knockout mice and their wild-type littermates were fed a high-fat,
      high-sucrose (HFHS) diet and treated with berberine by i.p. injection for five
      weeks. Mouse primary hepatocytes and human HepG2 cells were treated with
      berberine and then subjected to immunoblotting analysis and Oil Red O staining.
      KEY RESULTS: Berberine attenuated hepatic steatosis and controlled energy balance
      in mice by inducing autophagy and FGF21. These beneficial effects of berberine on
      autophagy and hepatic steatosis were abolished by a deficiency of the nutrient
      sensor SIRT1 in the liver of HFHS diet-fed obese mice and in mouse primary
      hepatocytes. SIRT1 is essential for berberine to potentiate autophagy and inhibit
      lipid storage in mouse livers in response to fasting. Mechanistically, the
      berberine stimulates SIRT1 deacetylation activity and induces autophagy in an
      autophagy protein 5-dependent manner. Moreover, the administration of berberine
      was shown to promote hepatic gene expression and circulating levels of FGF21 and
      ketone bodies in mice in a SIRT1-dependent manner. CONCLUSIONS AND IMPLICATIONS:
      Berberine acts in the liver to regulate lipid utilization and maintain whole-body
      energy metabolism by mediating autophagy and FGF21 activation. Hence, it has
      therapeutic potential for treating metabolic defects under nutritional overload,
      such as fatty liver diseases, type 2 diabetes and obesity.

PMID- 29065225
TI  - Structural investigation by tandem mass spectrometry analysis of a heterogeneous
      mixture of Lipid An isolated from the lipopolysaccharide of Aeromonas hydrophila
      SJ-55Ra.
AB  - RATIONALE: We report herein the electrospray ionization mass spectrometry (ESI
      MS) negative ion mode and low-energy collision-induced dissociation tandem mass
      spectrometry (CID-MS/MS) analysis of a mixture of lipid An isolated from the
      lipopolysaccharide (LPS) of a rough-resistant wild strain of the Gram-negative
      bacteria Aeromonas hydrophila grown in the presence of phages (SJ-55Ra). This
      investigation indicates that the presence of a mixture of lipid A acylated
      disaccharides, whose molecular structures were not relatively conserved, resulted
      from the incomplete LPS biosynthesis caused by the phage treatment. METHODS: The
      heterogeneous lipid An mixture from the LPS-SJ55Ra was obtained following growth
      of the Gram-negative bacteria Aeromonas hydrophila (SJ-55R) in the presence of
      phages and isolation by the aqueous phenol method. Following hydrolysis and
      purification of the lipopolysaccharide, ESI-MS and low-energy CID-MS/MS analyses
      were performed on a triple-quadrupole (QqQ) and a Fourier transform ion cyclotron
      resonance (FTICR) instrument. RESULTS: ESI-MS analysis suggested that this lipid
      An mixture contained eight molecular disaccharide anions and three monosaccharide
      anions. This series of lipid An was asymmetrically substituted with ((R)-14:0(3
      OH)) fatty acids located at O-3 and N-2 and with branched fatty acids: (Cl4:0(3
      (R)-O-C14:0)) and (C12:0(3-(R)-O-(14:0)) at the O-3' and N-2' positions.
      CONCLUSIONS: Tandem mass spectrometric analyses allowed the exact determination
      of the fatty acid acylation locations on the D-GlcpN disaccharide. The MS/MS
      results established that it was possible to selectively cleave C-O, C-N, and C-C
      bonds, together with glycosidic C-O and cross-ring cleavages, affording excellent
      structural analysis of lipid A biomolecules.

PMID- 29065226
TI  - Inkjet-Printed Nanocavities on a Photonic Crystal Template.
AB  - The last decade has witnessed the rapid development of inkjet printing as an
      attractive bottom-up microfabrication technology due to its simplicity and
      potentially low cost. The wealth of printable materials has been key to its
      widespread adoption in organic optoelectronics and biotechnology. However, its
      implementation in nanophotonics has so far been limited by the coarse resolution
      of conventional inkjet-printing methods. In addition, the low refractive index of
      organic materials prevents the use of "soft-photonics" in applications where
      strong light confinement is required. This study introduces a hybrid approach for
      creating and fine tuning high-Q nanocavities, involving the local deposition of
      an organic ink on the surface of an inorganic 2D photonic crystal template using
      a commercially available high-resolution inkjet printer. The controllability of
      this approach is demonstrated by tuning the resonance of the printed nanocavities
      by the number of printer passes and by the fabrication of photonic crystal
      molecules with controllable splitting. The versatility of this method is
      evidenced by the realization of nanocavities obtained by surface deposition on a
      blank photonic crystal. A new method for a free-form, high-density, material
      independent, and high-throughput fabrication technique is thus established with a
      manifold of opportunities in photonic applications.

PMID- 29065227
TI  - Increased energy differentially increases richness and abundance of optimal body
      sizes in deep-sea wood falls.
AB  - Theoretical and empirical studies suggest that the total energy available in
      natural communities influences body size as well as patterns of abundance and
      diversity. But the precise mechanisms underlying these relationships or how these
      three ecological properties relate remain elusive. We identify five hypotheses
      relating energy availability, body size distributions, abundance, and species
      richness within communities, and we use experimental deep-sea wood fall
      communities to test their predicted effects both on descriptors describing the
      species-richness-body-size distribution, and on trends in species richness within
      size classes over an energy gradient (size-class-richness relationships).
      Invertebrate communities were taxonomically identified, weighed, and counted from
      32 Acacia sp. logs ranging in size from 0.6 to 20.6 kg (corresponding to
      different levels of energy available), which were deployed at 3,203 m in the
      Northeast Pacific Ocean for 5 and 7 yr. Trends in both the species-richness-body
      size distribution and the size-class-richness distribution with increasing wood
      fall size provide support for the Increased Packing hypothesis: species richness
      increases with increasing wood fall size but only in the modal size class.
      Furthermore, species richness of body size classes reflected the abundance of
      individuals in that size class. Thus, increases in richness in the modal size
      class with increasing energy were concordant with increases in abundance within
      that size class. The results suggest that increases in species richness occurring
      as energy availability increases may be isolated to specific niches, e.g., the
      body size classes, especially in communities developing on discrete and
      energetically isolated resources such as deep sea wood falls.

PMID- 29065228
TI  - Myxofibrosarcoma of unusual sites.
AB  - BACKGROUND: Myxofibrosarcoma classically presents as a painless mass in the
      proximal extremities. Cutaneous myxofibrosarcomas arising in the head and neck
      and distal extremities are extremely uncommon. We present a series of 6 cases of
      myxofibrosarcoma presenting in the head and neck and acral locations. METHODS:
      Archives were searched using the term "myxofibrosarcoma" over a 6-year period
      (2009-2015). The clinicopathologic features of myxofibrosarcoma were recorded.
      Cases in the head and neck or acral locations were retrieved. When available, the
      patient's medical records were reviewed. RESULTS: Ninety-five cases of
      myxofibrosarcoma were identified over a 6-year period. Six patients were
      identified with myxofibrosarcoma arising in the head (n = 4, M:F 3:1), hand (n =
      1, F) and foot (n = 1, F). Each had typical features of myxofibrosarcoma. Two of
      the tumors on the head were high-grade and had multiple recurrences, while the
      remaining 2 were intermediate grade. Both acral tumors were intermediate grade
      and 1 recurred locally within a year of diagnosis. CONCLUSIONS: Myxofibrosarcoma
      may rarely involve the head and neck and acral locations, and presentation in
      these sites is a potential source of diagnostic difficulty. Recognition of the
      characteristic histologic features of myxofibrosarcoma in conjunction with
      judicial use of immunohistochemical stains should allow for accurate diagnosis.

PMID- 29065229
TI  - Prediction of disease progression in Miller Fisher and overlap syndromes.
AB  - Patients with Miller Fisher syndrome (MFS) may have a relatively mild clinical
      course or progress to Guillain-Barre syndrome (GBS) with limb weakness (MFS-GBS
      overlap syndrome). Other variants in this spectrum are GBS with ophthalmoparesis
      and Bickerstaff's Brainstem encephalitis (BBE). To compare the clinical course of
      MFS and overlap syndromes and to identify predictors of disease progression. In a
      prospective study of 170 patients with GBS and variant forms, 37 (22%) had a MFS,
      MFS-GBS overlap syndrome, ophthalmoplegic GBS or BBE. The clinical, serological,
      and electrophysiological features were compared. Twenty-three patients presented
      with MFS, of which 10 (43%) developed limb weakness (MFS-GBS overlap syndrome).
      All these transitions occurred in the first week after onset of symptoms. There
      were no differences in the clinical, electrophysiological and serological
      features at entry between MFS and MFS-GBS. Twelve patients had ophthalmoplegic
      GBS and the disease severity at nadir and outcome was worse than in the patients
      with a MFS-GBS overlap syndrome. No early predictors for progression from MFS to
      MFS-GBS overlap syndrome were found. All transitions occurred in the first week.
      This finding implicates that all patients with MFS need careful monitoring for at
      least 1 week.

PMID- 29065230
TI  - Comparing chemistry and bioactivity of burned vs. decomposed plant litter:
      different pathways but same result?
AB  - Litter burning and biological decomposition are oxidative processes co-occurring
      in many terrestrial ecosystems, producing organic matter with different chemical
      properties and differently affecting plant growth and soil microbial activity. We
      tested the chemical convergence hypothesis, i.e., materials with different
      initial chemistry converge toward a common profile, with similar biological
      effects, as the oxidative process advances, for burning and decomposition. We
      compared the molecular composition, assessed by 13 C NMR, of seven plant litter
      types either fresh, decomposed for 30, 90, 180 d in a microcosms incubation
      experiment, or heated at 100 degrees C, 200 degrees C, 300 degrees C, 400 degrees
      C, 500 degrees C for 30 minutes. We used litter water extracts (5% dry weight) as
      treatments in bioassays on plant (Lepidium sativum) and fungal (Aspergillus
      niger) growth, and a washed quartz sand amended with litter (0.5% dw) to assess
      heterotrophic respiration by flux chamber (i.e., [MUg of CO2 released].[g added
      litter]-1 .d-1 ). We observed different molecular variations for materials either
      burning (i.e., a sharp increase of aromatic C and a decrease of other fractions
      above 200 degrees C) or decomposing (i.e., early increase of alkyl, methoxyl, and
      N-alkyl C and decrease of O-alkyl and di-O-alkyl C fractions). Soil respiration
      and fungal growth decreased with litter age and heating severity, down to 20%
      relative to fresh litter. Plants were inhibited on fresh litter (on average 13%
      of the control), but recovered on aged (180 d) and heated (30 min at 500 degrees
      C) materials, up to 126% and 63% of the control, respectively. Correlation
      between the intensity of 13 C NMR signals in litter spectra and bioassay results
      showed that O-alkyl, methoxyl, and aromatic C fractions are crucial to understand
      organic matter effects, with plant response negatively affected by labile C but
      positively associated to lignification and pyrogenic C. The pattern of
      association of soil respiration and fungal growth to these C fractions was
      essentially opposite to that observed for plant root growth. Our findings suggest
      a functional convergence of decomposed and burned organic substrates, emerging
      from the balance between the bioavailability of labile C sources and the presence
      of recalcitrant and pyrogenic compounds, oppositely affecting different trophic
      levels.

PMID- 29065231
TI  - Aqueous PCDTBT:PC71 BM Photovoltaic Inks Made by Nanoprecipitation.
AB  - The fabrication of organic solar cells from aqueous dispersions of photoactive
      nanoparticles has recently attracted the interest of the photovoltaic community,
      since these dispersions offer an eco-friendly solution for the fabrication of
      solar cells, avoiding the use of toxic solvents. In this work, aqueous
      dispersions of pure poly[n-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2
      thienyl-2',1',3'-benzothiadiazole)] (PCDTBT) and [6,6]-phenyl-C71 -butyric acid
      methyl ester (PC71 BM) nanoparticles, as well as of composite PC71 BM:PCDTBT
      nanoparticles, are prepared using the nanoprecipitation postpolymerization
      method. These dispersions are subsequently used to form the active layer of
      organic photovoltaic cells. Thin films of PC71 BM and PCDTBT are obtained by
      spray deposition of the nanoparticles' dispersions, and are characterized using a
      combination of spectroscopic and microscopic techniques. Photovoltaics that
      incorporate these active layers are fabricated thereafter. The impact of the
      annealing temperature and of the composition of the active layer on the
      efficiency of the solar cells is studied.

PMID- 29065232
TI  - Sampling scales define occupancy and underlying occupancy-abundance relationships
      in animals.
AB  - Occupancy-abundance (OA) relationships are a foundational ecological phenomenon
      and field of study, and occupancy models are increasingly used to track
      population trends and understand ecological interactions. However, these two
      fields of ecological inquiry remain largely isolated, despite growing
      appreciation of the importance of integration. For example, using occupancy
      models to infer trends in abundance is predicated on positive OA relationships.
      Many occupancy studies collect data that violate geographical closure assumptions
      due to the choice of sampling scales and application to mobile organisms, which
      may change how occupancy and abundance are related. Little research, however, has
      explored how different occupancy sampling designs affect OA relationships. We
      develop a conceptual framework for understanding how sampling scales affect the
      definition of occupancy for mobile organisms, which drives OA relationships. We
      explore how spatial and temporal sampling scales, and the choice of sampling unit
      (areal vs. point sampling), affect OA relationships. We develop predictions using
      simulations, and test them using empirical occupancy data from remote cameras on
      11 medium-large mammals. Surprisingly, our simulations demonstrate that when
      using point sampling, OA relationships are unaffected by spatial sampling grain
      (i.e., cell size). In contrast, when using areal sampling (e.g., species atlas
      data), OA relationships are affected by spatial grain. Furthermore, OA
      relationships are also affected by temporal sampling scales, where the curvature
      of the OA relationship increases with temporal sampling duration. Our empirical
      results support these predictions, showing that at any given abundance, the
      spatial grain of point sampling does not affect occupancy estimates, but longer
      surveys do increase occupancy estimates. For rare species (low occupancy),
      estimates of occupancy will quickly increase with longer surveys, even while
      abundance remains constant. Our results also clearly demonstrate that occupancy
      for mobile species without geographical closure is not true occupancy. The
      independence of occupancy estimates from spatial sampling grain depends on the
      sampling unit. Point-sampling surveys can, however, provide unbiased estimates of
      occupancy for multiple species simultaneously, irrespective of home-range size.
      The use of occupancy for trend monitoring needs to explicitly articulate how the
      chosen sampling scales define occupancy and affect the occupancy-abundance
      relationship.

PMID- 29065233
TI  - ARTHUR ASBURY LECTURE: Chronic inflammatory demyelinating polyradiculoneuropathy:
      clinical aspects and new animal models of auto-immunity to nodal components.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune
      disorder of the peripheral nerves with clinical and immunological heterogeneity.
      Both cellular and humoral immune mechanisms against peripheral nerve antigens are
      considered to contribute to the pathogenesis of the disorder. Currently, the
      diagnosis of CIDP is based on clinical, laboratory and electrophysiological
      criteria. The field of CIDP recently underwent a major change with the
      identification of autoantibodies directed against paranodal (CNTN1, CASPR1 and
      NF155) and nodal (NF186/140) proteins. Over the last 5 years, correlations have
      been found between these autoantibodies and CIDP clinical subtypes including the
      likelihood of response to specific immunotherapies. Additionally, during this
      time a series of experimental studies have unraveled the underlying
      immunopathogenesis for CNTN1 and NF155 antibody associated CIDP. Although
      paranodal and nodal autoantibodies are only found in a small subset of patients
      with CIDP, the detection of these immune biomarkers should be incorporated in the
      evaluation of patients, considering the implications of their presence on
      prognosis, follow-up, and treatment decisions.

PMID- 29065234
TI  - Improvement of refractory pruritus after lipoprotein-apheresis in arthrogryposis
      renal failure-cholestasis syndrome.
AB  - Accumulation of bile acids can lead to invalidating pruritus in cholestatic
      patients. Few reports exist on the influence of lipoprotein-apheresis (LA) on
      plasma level of total bile acids (tBA). We report of significant decrease in tBA
      levels and drastic improvement of pruritus in a 5-year-old girl with
      arthrogryposis-renal failure-cholestasis syndrome. We present LA as a suitable
      rescue treatment option in therapy-refractory cholestasis-associated pruritus, at
      least as bridge until a long-term solution such as entero-biliary anastomosis or
      transplantation is possible.

PMID- 29065235
TI  - Comparison of Active Stimulating Electrodes of Sacral Neuromodulation.
AB  - OBJECTIVE: The goal of this study was to compare the motor response to sacral
      neuromodulation (SNM) with different pairs of stimulating electrodes in
      anesthetized and awake sheep. MATERIALS AND METHODS: Similar to SNM clinical use
      in humans, the InterStim(r) quadripolar tined lead was implanted adjacent to the
      S3 nerve root in sheep and bipolar stimulation was configured with one electrode
      negative and one electrode positive on the four contacts (0 most distal to
      device, 1, 2, and 3 most proximal). RESULTS: Electrode 3-cathode and electrode 0
      anode (3-/0+) stimulation had the lowest visual response threshold (0.46 +/-
      0.14V, anesthetized, 0.56 +/- 0.21V, conscious), representing the most sensitive
      stimulation. Stimulation on electrode 0 (0-/1+) had the highest response
      threshold among tested electrodes (2.70 +/- 0.23V, anesthetized, 3.38 +/- 0.96V,
      conscious). The order according to response threshold from low to high was 3 < 2
      < 1 < 0. The triggered response by 3-/0+ stimulation solely occurred in the
      perineum, tail, or bellows. In contrast, the 0-/1+ stimulation frequently evoked
      response in gluteal and thigh regions. The electromyographic activities from the
      anus were sensitive to low intensities of stimulation on electrode 3 (e.g., 3
      /0+, 3-/2+). CONCLUSIONS: Objective motor responses to SNM as a functional
      indicator for optimal lead placement may be used to demonstrate that the contact
      which is most proximal to the foramen (electrode 3) is an optimal electrode to
      trigger an "on-target" response to lower intensity stimulation. Data from this
      preclinical work suggest that there are several principles that may be referenced
      to simplify and expedite the programming process in clinical practice.

PMID- 29065236
TI  - Recent developments in nanotechnology transforming the agricultural sector: a
      transition replete with opportunities.
AB  - The applications and benefits of nanotechnology in the agricultural sector have
      attracted considerable attention, particularly in the invention of unique
      nanopesticides and nanofertilisers. The contemporary developments in
      nanotechnology are acknowledged and the most significant opportunities awaiting
      the agriculture sector from the recent scientific and technical literature are
      addressed. This review discusses the significance of recent trends in
      nanomaterial-based sensors available for the sustainable management of
      agricultural soil, as well as the role of nanotechnology in detection and
      protection against plant pathogens, and for food quality and safety. Novel
      nanosensors have been reported for primary applications in improving crop
      practices, food quality, and packaging methods, thus will change the agricultural
      sector for potentially better and healthier food products. Nanotechnology is well
      known to play a significant role in the effective management of phytopathogens,
      nutrient utilisation, controlled release of pesticides, and fertilisers. Research
      and scientific gaps to be overcome and fundamental questions have been addressed
      to fuel active development and application of nanotechnology. Together,
      nanoscience, nanoengineering, and nanotechnology offer a plethora of
      opportunities, proving a viable alternative in the agriculture and food
      processing sector, by providing a novel and advanced solutions. (c) 2017 Society
      of Chemical Industry.

PMID- 29065237
TI  - A New Polymer Electron Acceptor Based on Thiophene-S,S-dioxide Unit for Organic
      Photovoltaics.
AB  - For polymer solar cells (PSCs), efficient polymer electron acceptors are always
      based on strong electron-withdrawing imide unit or boron-nitrogen coordinative
      bond (B<-N). In this paper, a new polymer electron acceptor based on thiophene
      S,S-dioxide (TDO) unit is reported. The polymer electron acceptor, PBDT-TDO,
      consists of alternating TDO unit and 4,8-bis(alkylthienyl)-2-yl]benzo[1,2-b:4,5
      b']dithiophene (BDT) unit. For comparison, a control polymer with alternating BDT
      unit and thiophene unit has also been synthesized. Replacing thiophene unit with
      TDO unit in the polymer backbone leads to large downshift of lowest unoccupied
      molecular orbital/highest occupied molecular orbital energy levels by 0.9 eV/0.4
      eV, which is attributed to the dearomatization and electron deficiency of TDO
      unit. The replacement also leads to redshift of absorption spectra by ~110 nm.
      PSC device with PBDT-TDO as the electron acceptor shows photovoltaic response
      with the preliminary power conversion efficiency of 0.64%. This work suggests a
      new approach to design polymer electron acceptors using the TDO unit.

PMID- 29065240
TI  - Bifurcated Nickel-Catalyzed Functionalizations: Heteroarene C-H Activation with
      Allenes.
AB  - A unified strategy for nickel(0)-catalyzed C-H allylations, alkenylations, and
      dienylations has been realized through versatile hydroarylations of allenes with
      ample scope. Thus, an inexpensive nickel catalyst modified with a N-heterocyclic
      carbene ligand enabled the direct transformation of C-H bonds of biologically
      relevant imidazole and purine derivatives with full control of regio- and
      chemoselectivity.

PMID- 29065241
TI  - Diastereoselective Construction of Densely Functionalized 1-Halocyclopentenes
      Using an Alkynyl Halo-Prins/Halo-Nazarov Cyclization Strategy.
AB  - A diastereoselective two-step strategy for the synthesis of densely
      functionalized 1-halocyclopentenes with several chiral centers has been
      developed. In the first step, a multicomponent alkynyl halo-Prins reaction joins
      an enyne, a carbonyl derivative, and either a chloride, bromide, or iodide to
      produce a cyclic ether intermediate. In the subsequent step, the intermediate is
      ionized to generate a halopentadienyl cation, which undergoes an interrupted halo
      Nazarov cyclization. The products contain three new contiguous stereogenic
      centers, generated with a high level of stereocontrol, as well as a vinyl halide
      allowing for additional functionalization. The strategy creates two new carbon
      carbon bonds, one carbon-halide bond, and one carbon-oxygen bond.

PMID- 29065242
TI  - Aging of the venous valves as a new risk factor for venous thrombosis in the
      elderly: the BATAVIA study.
AB  - : Essentials Risk of venous thrombosis (VT) related to valve thickness and
      valvular reflux in unknown. Venous valves and reflux were measured by
      ultrasonography in cases and controls aged 70+. Risk of VT was associated with
      increased valve thickness and valvular reflux >1second. Thickening of valves is a
      generic process: there was no difference between right and left legs. SUMMARY:
      Background Increasing age is the strongest risk factor for venous thrombosis
      (VT). Increasing age has been related to a thickening of the venous valves and a
      decreased valvular function. The association between valve thickness and the risk
      of VT is not known. Objectives To assess the association between increased valve
      thickness and valve closure time (VCT) and the risk of VT. Methods Analyses were
      performed in the BATAVIA study, including 70 cases aged 70 + with a first VT and
      96 controls. We performed an ultrasound examination of the valves in the
      popliteal veins. The valves were imaged with a 9 MHz linear probe using B-mode
      ultrasonography. VCT was measured as an indicator for valve function using an
      automatic inflatable cuff. To estimate the risk of VT, valve thickness was
      dichotomized at the 90th percentile as measured in controls and VCT was
      dichotomized at 1 s. Results Mean valve thickness of controls was similar in the
      left (0.36 mm, 95% CI 0.34-0.37) and right (0.36 mm, 95% CI 0.35-0.38) leg. In 45
      cases a valve was observed in the contralateral leg with a mean valve thickness
      of 0.39 mm (95% CI 0.36-0.42). Cases had an increased valve thickness compared
      with controls: mean difference 0.028 mm (95%CI 0.001-0.055). Valve thickness >
      90th percentile increased the risk of VT 2.9-fold. Mean VCT in controls was 0.38
      s, in contralateral leg of cases 0.58 s. VCT > 1 s increased the risk of VT 2.8
      fold (95% CI 0.8-10.4). Conclusions Risk of VT was associated with increased
      valve thickness and valvular reflux of > 1 s.

PMID- 29065239
TI  - Optothermally Reversible Carbon Nanotube-DNA Supramolecular Hybrid Hydrogels.
AB  - Supramolecular hydrogels (SMHs) are three-dimensional constructs wherein the
      majority of the volume is occupied by water. Since the bonding forces between the
      components of SMHs are noncovalent, SMH properties are often tunable, stimuli
      responsive, and reversible, which enables applications including triggered drug
      release, sensing, and tissue engineering. Meanwhile, single-walled carbon
      nanotubes (SWCNTs) possess superlative electrical and thermal conductivities,
      high mechanical strength, and strong optical absorption at near-infrared
      wavelengths that have the potential to add unique functionality to SMHs. However,
      SWCNT-based SMHs have thus far not realized the potential of the optical
      properties of SWCNTs to enable reversible response to near-infrared irradiation.
      Here, we present a novel SMH architecture comprised solely of DNA and SWCNTs,
      wherein noncovalent interactions provide structural integrity without
      compromising the intrinsic properties of SWCNTs. The mechanical properties of
      these SMHs are readily tuned by varying the relative concentrations of DNA and
      SWCNTs, which varies the cross-linking density as shown by molecular dynamics
      simulations. Moreover, the SMH gelation transition is fully reversible and can be
      triggered by a change in temperature or near-infrared irradiation. This work
      explores a new regime for SMHs with potential utility for a range of applications
      including sensors, actuators, responsive substrates, and 3D printing.

PMID- 29065243
TI  - Intramolecular Thioether Migration in the Rhodium-Catalyzed Ene
      Cycloisomerization of Alkenylidenecyclopropanes by a Metal-Mediated beta-Sulfide
      Elimination.
AB  - Reported is the first example of a rhodium-mediated beta-sulfide elimination,
      which represents a new mode of reactivity for late-transition-metal chemistry.
      This serendipitous discovery facilitates an ene-cycloisomerization of allylic
      sulfide-containing alkenylidenecyclopropanes (ACPs) to afford five-membered carbo
      and heterocyclic rings with concomitant intramolecular thioether migration.
      Interestingly, similar selectivity is obtained with both E- and Z-allylic
      sulfides and the reaction is also feasible with an allylic selenide. Mechanistic
      studies are consistent with an inner-sphere transfer of the sulfide, which is
      remarkable given the propensity for sulfides to poison transition-metal
      catalysts. Finally, this type of atom-economical rearrangement is envisioned to
      prompt the development of related processes given the utility of sulfides in
      target-directed synthesis.

PMID- 29065245
TI  - Manganese Complexes for (De)Hydrogenation Catalysis: A Comparison to Cobalt and
      Iron Catalysts.
AB  - The sustainable use of the resources on our planet is essential. Noble metals are
      very rare and are diversely used in key technologies, such as catalysis.
      Manganese is the third most abundant transition metal of the Earth's crust and
      based on the recently discovered impressive reactivity in hydrogenation and
      dehydrogenation reactions, is a potentially useful noble-metal "replacement". The
      hope of novel selectivity profiles, not possible with noble metals, is also an
      aim of such a "replacement". The reactivity of manganese complexes in
      (de)hydrogenation reactions was demonstrated for the first time in 2016. Herein,
      we summarize the work that has been published since then and especially discuss
      the importance of homogeneous manganese catalysts in comparison to cobalt and
      iron catalysts.

PMID- 29065244
TI  - Cooperative Multifunctional Catalysts for Nitrone Synthesis: Platinum
      Nanoclusters in Amine-Functionalized Metal-Organic Frameworks.
AB  - Nitrones are key intermediates in organic synthesis and the pharmaceutical
      industry. The heterogeneous synthesis of nitrones with multifunctional catalysts
      is extremely attractive but rarely explored. Herein, we report ultrasmall
      platinum nanoclusters (PtNCs) encapsulated in amine-functionalized Zr metal
      organic framework (MOF), UiO-66-NH2 (Pt@UiO-66-NH2 ) as a multifunctional
      catalyst in the one-pot tandem synthesis of nitrones. By virtue of the
      cooperative interplay among the selective hydrogenation activity provided by the
      ultrasmall PtNCs and Lewis acidity/basicity/nanoconfinement endowed by UiO-66-NH2
      , Pt@UiO-66-NH2 exhibits remarkable activity and selectivity, in comparison to
      Pt/carbon, Pt@UiO-66, and Pd@UiO-66-NH2 . Pt@UiO-66-NH2 also outperforms Pt
      nanoparticles supported on the external surface of the same MOF (Pt/UiO-66-NH2 ).
      To our knowledge, this work demonstrates the first examples of one-pot synthesis
      of nitrones using recyclable multifunctional heterogeneous catalysts.

PMID- 29065246
TI  - A review of the reporting of web searching to identify studies for Cochrane
      systematic reviews.
AB  - The literature searches that are used to identify studies for inclusion in a
      systematic review should be comprehensively reported. This ensures that the
      literature searches are transparent and reproducible, which is important for
      assessing the strengths and weaknesses of a systematic review and re-running the
      literature searches when conducting an update review. Web searching using search
      engines and the websites of topically relevant organisations is sometimes used as
      a supplementary literature search method. Previous research has shown that the
      reporting of web searching in systematic reviews often lacks important details
      and is thus not transparent or reproducible. Useful details to report about web
      searching include the name of the search engine or website, the URL, the date
      searched, the search strategy, and the number of results. This study reviews the
      reporting of web searching to identify studies for Cochrane systematic reviews
      published in the 6-month period August 2016 to January 2017 (n = 423). Of these
      reviews, 61 reviews reported using web searching using a search engine or website
      as a literature search method. In the majority of reviews, the reporting of web
      searching was found to lack essential detail for ensuring transparency and
      reproducibility, such as the search terms. Recommendations are made on how to
      improve the reporting of web searching in Cochrane systematic reviews.

PMID- 29065247
TI  - International collaborative study for the calibration of proposed International
      Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant,
      human, plain.
AB  - : Essentials Two candidate International Standards for thromboplastin (coded
      RBT/16 and rTF/16) are proposed. International Sensitivity Index (ISI) of
      proposed standards was assessed in a 20-centre study. The mean ISI for RBT/16 was
      1.21 with a between-centre coefficient of variation of 4.6%. The mean ISI for
      rTF/16 was 1.11 with a between-centre coefficient of variation of 5.7%. SUMMARY:
      Background The availability of International Standards for thromboplastin is
      essential for the calibration of routine reagents and hence the calculation of
      the International Normalized Ratio (INR). Stocks of the current Fourth
      International Standards are running low. Candidate replacement materials have
      been prepared. This article describes the calibration of the proposed Fifth
      International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for
      thromboplastin, recombinant, human, plain (coded rTF/16). Methods An
      international collaborative study was carried out for the assignment of
      International Sensitivity Indexes (ISIs) to the candidate materials, according to
      the World Health Organization (WHO) guidelines for thromboplastins and plasma
      used to control oral anticoagulant therapy with vitamin K antagonists. Results
      Results were obtained from 20 laboratories. In several cases, deviations from the
      ISI calibration model were observed, but the average INR deviation attributabled
      to the model was not greater than 10%. Only valid ISI assessments were used to
      calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21
      (between-laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for
      rTF/16 was 1.11 (between-laboratory CV: 5.7%). Conclusions The between-laboratory
      variation of the ISI for candidate material RBT/16 was similar to that of the
      Fourth International Standard (RBT/05), and the between-laboratory variation of
      the ISI for candidate material rTF/16 was slightly higher than that of the Fourth
      International Standard (rTF/09). The candidate materials have been accepted by
      WHO as the Fifth International Standards for thromboplastin, rabbit plain, and
      thromboplastin, recombinant, human, plain.

PMID- 29065248
TI  - The 35th Manfred Donike workshop on doping analysis.

PMID- 29065250
TI  - The van der Waals Interactions of n-Alkanethiol-Covered Surfaces: From Planar to
      Curved Surfaces.
AB  - The van der Waals (vdW) interactions of n-alkanethiols (ATs) adsorbed on planar
      Au(111) and Au(100) surfaces and curved Au nanoparticles of different diameters
      are reported. By means of electrochemical measurements and molecular dynamic
      calculations, the increase in the average geometrical curvature of the surface
      influences the global interactions, that is, decreasing vdW interactions between
      neighboring molecules. Small NPs do not present the same electrochemical behavior
      as planar surfaces. The transition between nanoparticle to flat surface
      electrochemical response is estimated to occur at a circa 13-20 nm diameter
      range.

PMID- 29065251
TI  - All aboard: the Journal's journey to broader content-ment.

PMID- 29065252
TI  - Why 'mood stabilizer' needs stability: Polar views on its utility.

PMID- 29065249
TI  - Fundamentals of Laser-Based Hydrogel Degradation and Applications in Cell and
      Tissue Engineering.
AB  - The cell and tissue engineering fields have profited immensely through the
      implementation of highly structured biomaterials. The development and
      implementation of advanced biofabrication techniques have established new avenues
      for generating biomimetic scaffolds for a multitude of cell and tissue
      engineering applications. Among these, laser-based degradation of biomaterials is
      implemented to achieve user-directed features and functionalities within
      biomimetic scaffolds. This review offers an overview of the physical mechanisms
      that govern laser-material interactions and specifically, laser-hydrogel
      interactions. The influences of both laser and material properties on efficient,
      high-resolution hydrogel degradation are discussed and the current application
      space in cell and tissue engineering is reviewed. This review aims to acquaint
      readers with the capability and uses of laser-based degradation of biomaterials,
      so that it may be easily and widely adopted.

PMID- 29065254
TI  - Erratum.

PMID- 29065253
TI  - Hepatic stellate cell autophagy in acute liver injury: A novel role for nitric
      oxide?

PMID- 29065255
TI  - Response to Non-invasive fibrosis markers for chronic hepatitis B in sub-Saharan
      Africa.

PMID- 29065256
TI  - Combining GP73 with liver stiffness measurements: A proof-of-concept for non
      invasive fibrosis assessment in antiviral-naive HBV patients.

PMID- 29065257
TI  - Response to Profile and outcome of first 109 cases of paediatric acute liver
      failure at a specialized paediatric liver unit in India: Methodological issues.

PMID- 29065259
TI  - An All-Silk-Derived Dual-Mode E-skin for Simultaneous Temperature-Pressure
      Detection.
AB  - Flexible skin-mimicking electronics are highly desired for development of smart
      human-machine interfaces and wearable human-health monitors. Human skins are able
      to simultaneously detect different information, such as touch, friction,
      temperature, and humidity. However, due to the mutual interferences of sensors
      with different functions, it is still a big challenge to fabricate
      multifunctional electronic skins (E-skins). Herein, a combo temperature-pressure
      E-skin is reported through assembling a temperature sensor and a strain sensor in
      both of which flexible and transparent silk-nanofiber-derived carbon fiber
      membranes (SilkCFM) are used as the active material. The temperature sensor
      presents high temperature sensitivity of 0.81% per centigrade. The strain sensor
      shows an extremely high sensitivity with a gauge factor of ~8350 at 50% strain,
      enabling the detection of subtle pressure stimuli that induce local strain.
      Importantly, the structure of the SilkCFM in each sensor is designed to be
      passive to other stimuli, enabling the integrated E-skin to precisely detect
      temperature and pressure at the same time. It is demonstrated that the E-skin can
      detect and distinguish exhaling, finger pressing, and spatial distribution of
      temperature and pressure, which cannot be realized using single mode sensors. The
      remarkable performance of the silk-based combo temperature-pressure sensor,
      together with its green and large-scalable fabrication process, promising its
      applications in human-machine interfaces and soft electronics.

PMID- 29065258
TI  - Characterization of body composition and definition of sarcopenia in patients
      with alcoholic cirrhosis: A computed tomography based study.
AB  - BACKGROUND: Alterations in body composition (BC) as loss of fat and muscle mass
      (sarcopenia) are associated with poor outcome in alcoholic cirrhosis (ALC).
      Prevalence of sarcopenia depends upon the method of assessment. Computed
      Tomography (CT) is a gold standard tool for assessing BC. AIM: To characterize BC
      and define sarcopenia in ALC patients using CT. METHODS: Single slice CT images
      at L3 vertebrae of healthy controls (HC) - organ transplant donors and ALC
      patients were analysed to give cross-sectional area of five skeletal muscles
      normalized for height -skeletal muscle index (SMI; cm2 /m2 ), area of
      subcutaneous (SAT;cm2 ) and visceral adipose tissue (VAT;cm2 ). Cut-offs for
      defining sarcopenia was established at 2SD below the mean of HC. HC were compared
      with Child A-compensated (C) and Child B+C-decompensated (DC) patients. RESULTS:
      Cut-offs of SMI derived from HC (n = 275; M: 50%; age 32.2 +/- 9.8 years; BMI
      24.2 +/- 3.2 Kg/m2 ) were 36.54 in males and 30.21 in females. Sarcopenia was
      found in 12.8% of ALC patients [n = 148; C (31.8%): DC (68.2%); M: 100%; age 46.6
      +/- 9.7 years; BMI 24.5 +/- 4.4]. Compared to HC, compensated patients had higher
      adiposity and comparable muscularity; decompensated patients had significantly
      lower muscle and also fat mass compared to both HC and compensated patients. HC
      vs C vs DC: SAT (140 +/- 82 vs 177.3 +/- 11 vs 112 +/- 8.2); VAT (96.5 +/- 6.5 vs
      154.9 +/- 8.7 vs 87.5 +/- 6.5) and SMI (52.1 +/- 0.9 vs 49.6 +/- 1.2 vs 46 +/-
      0.9). CONCLUSIONS: Compensated ALC have increased adiposity and relatively
      preserved muscularity but decompensation leads to loss of both muscle and fat
      mass. Prevalence of sarcopenia, based on derived ethnic cut-offs was 12.8%.

PMID- 29065260
TI  - Isothiocyanyl Alanine as a Synthetic Intermediate for the Synthesis of Thioureayl
      Alanines and Subsequent Aminotetrazolyl Alanines.
AB  - The synthesis of unnatural amino acids with small side-chain functionalities
      usable for further transformations is highly demanding for the expansion of the
      genetic code and other possible biotechnological applications. To this end, we
      wanted to report the utility of an unexplored unnatural amino acid, isothiocyanyl
      alanine (NCSAla = Ita), for the synthesis of another class of unnatural amino
      acids, thioureayl alanines (TUAla = Tua). The synthesis of a third class of
      unnatural amino acids, amino tetrazolyl alanines (ATzAla = Ata), in a very good
      yield was subsequently achieved utilizing thioureayl alanines. Thus, a variety of
      aliphatic- and aromatic-substituted thioureayl alanines and aromatic-substituted
      amino tetrazolyl alanines were successfully synthesized in good to excellent
      yields. The photophysical properties of three of the fluorescent unnatural amino
      acids from two classes were also studied and presented herein.

PMID- 29065261
TI  - Identification of Lipid Biomarkers To Discriminate between the Different
      Production Systems for Asiago PDO Cheese.
AB  - The lipid fraction of Asiago Protected Designation of Origin (PDO) cheese was
      analyzed to identify specific biomarkers of its main production systems through a
      canonical discriminant analysis. The three main production systems of the cheese
      were considered. Two were located in the upland (UL): pasture-based (P-UL) vs hay
      based total mixed rations (H-UL). The third was located in the lowland (LL) and
      processed milk from cows fed maize silage-based rations (maize silage lowland: MS
      LL). The discriminant analysis selected nine fatty acids and vitamin A as lipid
      biomarkers useful to separate the three production systems. High contents of
      conjugated linoleic acids, anteiso-C15:0, and vitamin A were discriminant factors
      for P-UL cheese. The separation between H-UL and MS-LL cheese was less marked
      with the former having the higher content of conjugated linoleic acids and some
      polyunsaturated n-6 fatty acids and with the latter being identified by
      cyclopropane fatty acid and C9:0.

PMID- 29065263
TI  - The Palladium-Catalyzed Intramolecular Alder-Ene Reactions of O- and N-Linked 1,6
      Enynes Incorporating Triethylsilyl Capping Groups.
AB  - A series of O- and N-linked 1,6-enynes (e.g., 11) have been prepared with each
      subjected to a palladium-catalyzed intramolecular Alder-ene (IMAE) reaction, thus
      producing the isomeric and cyclic 1,4-diene (e.g., 12). These processes proceed
      most effectively when a triethylsilyl group is attached to the alkyne moiety and
      so generating alkenylsilanes that can be manipulated in various useful ways,
      including via iododesilylation (to give, for example, iodoalkene 62).

PMID- 29065262
TI  - Unlocking Endosomal Entrapment with Supercharged Arginine-Rich Peptides.
AB  - Endosomal entrapment is a common bottleneck in various macromolecular delivery
      approaches. Recently, the polycationic peptide dfTAT was identified as a reagent
      that induces the efficient leakage of late endosomes and, thereby, enhances the
      penetration of macromolecules into the cytosol of live human cells. To gain
      further insights into the features that lead to this activity, the role of
      peptide sequence was investigated. We establish that the leakage activity of
      dfTAT can be recapitulated by polyarginine analogs but not by polylysine
      counterparts. Efficiencies of peptide endocytic uptake increase linearly with the
      number of arginine residues present. In contrast, peptide cytosolic penetration
      displays a threshold behavior, indicating that a minimum number of arginines is
      required to induce endosomal escape. Increasing arginine content above this
      threshold further augments delivery efficiencies. Yet, it also leads to
      increasing the toxicity of the delivery agents. Together, these data reveal a
      relatively narrow arginine-content window for the design of optimally active
      endosomolytic agents.

PMID- 29065264
TI  - Oxidant and Transition-Metal-Free Photoinduced Direct Oxidative Annulation of 1
      Aryl-2-(furan/thiophen-2-yl)butane-1,3-diones.
AB  - A photoinduced direct oxidative annulation of 1-aryl-2-(furan/thiophen-2
      yl)butane-1,3-diones and ethyl-2-(furan-2-yl)-3-oxo-3-(aryl-2-yl)propanoates in
      EtOH without the need for any transition metals and oxidants provided access to
      highly functionalized polyheterocyclic 1-(5-hydroxynaphtho[2,1-b]furan-4
      yl)ethanones and 1-(5-hydroxyfuran/thieno/pyrrolo[3,2-e]benzofuran-4
      yl)ethanones. The phenomenon of excited-state intramolecular proton transfer
      (ESIPT) was observed for both 1-(5-hydroxynaphtho[2,1-b]furan-4-yl)ethanone and 1
      (5-hydroxy furan/thieno/pyrrolo[3,2-e]benzofuran-4-yl)ethanone analogues.

PMID- 29065266
TI  - Protecting-Group-Free Synthesis of 1-Phenylisoquinolin-4-ols: Thermal Cyclization
      of Methyl 2-[(Diphenylmethylidene)amino]acetates.
AB  - A protecting-group-free synthetic approach to 1-phenylisoquinolin-4-ols was
      developed by the intramolecular thermal cyclization of methyl 2
      [(diphenylmethylidene)amino]acetates. R1 and R2 substituents were found to affect
      the required reaction temperatures, time, and yields of the cyclized products.
      The reactivity of the Schiff bases increased upon introduction of alpha-benzoyl
      and alpha-ester groups (R2). The cyclization yield also depended on the position
      of the R1 substituents on the phenyl groups.

PMID- 29065265
TI  - Energetics of Glutamate Binding to an Ionotropic Glutamate Receptor.
AB  - Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are
      responsible for the majority of excitatory transmission at the synaptic cleft.
      Mechanically speaking, agonist binding to the ligand binding domain (LBD)
      activates the receptor by triggering a conformational change that is transmitted
      to the transmembrane region, opening the ion channel pore. We use fully atomistic
      molecular dynamics simulations to investigate the binding process in the alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, an iGluR
      subtype. The string method with swarms of trajectories was applied to calculate
      the possible pathways glutamate traverses during ligand binding. Residues
      peripheral to the binding cleft are found to metastably bind the ligand prior to
      ligand entry into the binding pocket. Umbrella sampling simulations were
      performed to compute the free energy barriers along the binding pathways. The
      calculated free energy profiles demonstrate that metastable interactions
      contribute substantially to the energetics of ligand binding and form local
      minima in the overall free energy landscape. Protein-ligand interactions at sites
      outside of the orthosteric agonist-binding site may serve to lower the transition
      barriers of the binding process.

PMID- 29065267
TI  - The prognostic importance of TGF-beta, TGF-beta receptor, and fascin in childhood
      solid tumors.
AB  - Fascin plays a role in tumor metastasis under the influence of TGF-beta, each
      potentiating the effect of the other. We retrospectively investigated whether
      there was a prognostic relationship between TGF-beta and fascin, and disease
      stage, local recurrence, metastasis tendency, and response to treatment. Twelve
      neuroblastomas, 17 osteosarcomas, 14 Ewing's sarcomas, 15 rhabdomyosarcoma cases,
      and 8 rare solid tumors were included. Serum TGF-beta levels were high at the
      time of diagnosis in all groups (p = .015) and decreased significantly during
      remission (p = .008). Serum TGF-beta values in the relapse period rarely reached
      high levels at the time of diagnosis and even stayed under the control group
      values (p = .017). When TGF-beta receptor expression in tumor tissues was
      evaluated, the association of TGF-beta receptor positivity with metastatic
      disease and advanced stage was striking. We found that 88% of rhabdomyosarcoma
      cases with alveolar histopathology expressed the TGF-beta receptor, and the
      association between TGF-beta receptor positivity and alveolar histopathology
      seemed to be a negative prognostic marker. When fascin levels were evaluated in
      childhood solid tumor tissue, the risk of relapse increased when the fascin total
      score at diagnosis was >4. This is one of the few studies including prognostic
      markers such as serum TGF-beta, tissue TGF-beta, TGF-beta receptor, and fascin in
      pediatric solid tumors. Considering the poor prognosis of advanced stage
      pediatric solid tumors and the need for biomarkers to predict which patient might
      need more intensive therapy or warrant closer follow-up afterward, we think that
      TGF-beta, TGF-beta receptor, and fascin expression have an important prognostic
      role.

PMID- 29065268
TI  - High-Level Disinfection of Otorhinolaryngology Clinical Instruments: An
      Evaluation of the Efficacy and Cost-effectiveness of Instrument Storage.
AB  - Objectives Despite increasing interest in individual instrument storage, risk of
      bacterial cross-contamination of otorhinolaryngology clinic instruments has not
      been assessed. This study is the first to determine the clinical efficacy and
      cost-effectiveness of standard high-level disinfection and clinic instrument
      storage. Methods To assess for cross-contamination, surveillance cultures of
      otorhinolaryngology clinic instruments subject to standard high-level
      disinfection and storage were obtained at the start and end of the outpatient
      clinical workday. Rate of microorganism recovery was compared with cultures of
      instruments stored in individual peel packs and control cultures of contaminated
      instruments. Based on historical clinic data, the direct allocation method of
      cost accounting was used to determine aggregate raw material cost and additional
      labor hours required to process and restock peel-packed instruments. Results
      Among 150 cultures of standard high-level disinfected and co-located clinic
      instruments, 3 positive bacterial cultures occurred; 100% of control cultures
      were positive for bacterial species ( P < .001). There was no statistical
      difference between surveillance cultures obtained before and after the clinic
      day. While there was also no significant difference in rate of contamination
      between peel-packed and co-located instruments, peel packing all instruments
      requires 6250 additional labor hours, and conservative analyses place the cost of
      individual semicritical instrument storage at $97,852.50 per year. Discussion
      With in vitro inoculation of >200 otorhinolaryngology clinic instruments, this
      study demonstrates that standard high-level disinfection and storage are equally
      efficacious to more time-consuming and expensive individual instrument storage
      protocols, such as peel packing, with regard to bacterial contamination.
      Implications for Practice Standard high-level disinfection and storage are
      equally effective to labor-intensive and costly individual instrument storage
      protocols.

PMID- 29065269
TI  - The Brugmann Fatigue Scale: An Analogue to the Epworth Sleepiness Scale to
      Measure Behavioral Rest Propensity.
AB  - BACKGROUND: While often confused, fatigue (as opposed to sleepiness) mostly
      requires rest, not sleep, to recover from. Clinical evaluations of fatigue mainly
      rely on assessments of symptom intensity, however without taking into account the
      need to engage in behavioral countermeasures. We therefore developed an 8-item 4
      point Likert scale (the Brugmann Fatigue Scale; BFS) sharing a similar conceptual
      background with the Epworth Sleepiness Scale (ESS), assessing mental and physical
      fatigue and focusing specifically on rest propensity. METHODS: Out of 496
      consecutive patients addressed to the sleep unit of an academic hospital, we
      selected a sample of 295 hypnotic-free subjects (122 females). The present study
      examines (a) the psychometric properties of the BFS and (b) measurement
      invariance regarding perceived sleep quality, in parallel with common sleepiness
      and fatigue scales (ESS and Fatigue Severity Scale; FSS). In addition, (c)
      correlations of the BFS with clinical scales and polysomnographic variables were
      explored descriptively. RESULTS: Rasch analyses revealed that the BFS possesses
      sound psychometric characteristics (rating scale functioning, item fit,
      dimensionality and measurement invariance) allowing for valid, reliable, linear
      and unidimensional measurement of mental and physical rest propensity,
      irrespective of perceived sleep quality, age, or gender. In addition, the BFS was
      significantly correlated to periodic limb movements during sleep and inversely to
      REM sleep duration. For both mental and physical subscales, scores above 6 are
      proposed as cutoff values. CONCLUSION: In analogy to the ESS, the BFS shows to be
      a unique and precise instrument assessing symptomatic fatigue with respect to
      rest propensity.

PMID- 29065270
TI  - Medial Meniscus Resection Increases and Medial Meniscus Repair Preserves Anterior
      Knee Laxity: A Cohort Study of 4497 Patients With Primary Anterior Cruciate
      Ligament Reconstruction.
AB  - BACKGROUND: There are still controversies regarding the effects on knee laxity of
      additional meniscus resection or repair in the setting of anterior cruciate
      ligament reconstruction (ACLR). Hypothesis/Purpose: The purpose was to determine
      the effects on knee laxity of resection or repair of medial meniscus (MM) or
      lateral meniscus (LM) injuries in the ACLR knee. The hypothesis was that patients
      with an additional meniscus resection would have significantly increased
      postoperative knee laxity versus that of an isolated ACLR, whereas patients with
      meniscus repair would have laxity comparable to that of an isolated ACLR. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: The KT-1000 arthrometer,
      with an anterior tibial load of 134 N, was used to evaluate knee laxity
      preoperatively and at 6-month postoperative follow-up for a total of 4497
      patients with primary hamstring tendon ACLR. Patients with isolated ACLR or ACLR
      with additional MM resection, MM repair, LM resection, LM repair, or MM plus LM
      resection were compared, with the isolated ACLR group as a control. RESULTS: All
      patients showed a significant reduction of knee laxity preoperatively (3.6 +/-
      3.1 mm) to postoperatively (1.9 +/- 2.2 mm) ( P < 0.0001). Patients who had an
      ACLR with either an MM resection (2.2 +/- 2.55 mm) or MM + LM resection (2.35 +/-
      2.30 mm) showed significant increased postoperative knee laxity versus isolated
      ACLR (1.74 mm +/- 2.11 mm) ( P < 0.05), whereas patients with MM repair (1.69 +/-
      2.37 mm) did not show significantly different knee laxity when compared with the
      control group ( P > 0.05). LM resection or repair did not significantly affect
      knee laxity. Significantly more surgical failures, defined as side-to-side
      difference >5 mm, were found in the ACLR + MM resection group and the ACLR + MM +
      LM resection group. CONCLUSION: In ACLR, additional MM resection increased
      whereas MM repair preserved knee laxity in comparison with the ACLR knee with
      intact menisci. Neither LM resection or LM repair showed a significant effect on
      knee laxity. Surgeons should make every effort to repair the meniscus whenever
      possible to avoid the residual postoperative laxity present in the meniscus
      deficient knee.

PMID- 29065272
TI  - Clinical Practice Guidelines: AAO-HNSF Process for CPG Development and Topic
      Selection.
AB  - The American Academy of Otolaryngology-Head and Neck Surgery has been developing
      clinical practice guidelines (CPGs) for use by its members and the public. The
      process of CPG development and the selection of topics for CPGs can be confusing.
      This commentary attempts to clarify this process and delineate the issues that
      are considered in topic selection.

PMID- 29065271
TI  - Hamstring Graft Incorporation According to the Length of the Graft Inside
      Tunnels.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction with a quadrupled
      semitendinosus (ST4) graft is an evolution of the standard technique with 2
      hamstring tendons (semitendinosus + gracilis [STG]). However, there is no
      published comparison of how well these 2 types of hamstring grafts are
      incorporated into the bone tunnels. Because the ST4 graft is shorter, there is
      less graft material inside the tunnels. PURPOSE: To use magnetic resonance
      imaging (MRI) to compare graft incorporation in the tibial bone tunnels 1 year
      after ACL reconstruction with either an STG graft or ST4 graft. STUDY DESIGN:
      Cohort study; Level of evidence, 2. METHODS: Sixty-two patients who underwent ACL
      reconstruction were enrolled prospectively: 31 with an ST4 graft and 31 with an
      STG graft. The same surgical technique, fixation method, and postoperative
      protocol were used in both groups. Graft incorporation and ligamentization were
      evaluated with MRI after 1 year of follow-up. The following parameters were
      evaluated: signal-to-noise quotient (SNQ), tibial tunnel enlargement, signal
      intensity at the bone-graft interface, and graft signal according to the Howell
      scale. The number of participants needed to show that the mean SNQ did not differ
      between the 2 techniques was 31 in each group (with a 1-sided alpha of 2.5% and a
      1-sided beta of 10.0%). The Student t test was used to compare the distribution
      of continuous secondary endpoints. RESULTS: The mean SNQ was 5.2 +/- 4.5 for the
      STG group and 5.9 +/- 3.7 for the ST4 group ( P = .5100). The mean tibial tunnel
      widening was 93.7% +/- 51.7% for the STG group versus 80.0% +/- 42.9% for the ST4
      group ( P = .2605). The groups did not differ in signal intensity at the bone
      graft interface ( P = .7502) or in graft signal according to the Howell scale ( P
      = .4544). CONCLUSION: At the 1-year postoperative follow-up, incorporation and
      ligamentization of the STG and ST4 grafts were the same based on MRI analysis.
      The results were at least as good with the ST4 technique as with the standard STG
      technique in terms of incorporation and ligamentization.

PMID- 29065273
TI  - Endoscopic Sinus Surgery Improves Sleep Quality in Chronic Rhinosinusitis: A
      Systematic Review and Meta-analysis.
AB  - Objective Up to 75% of patients with chronic rhinosinusitis (CRS) suffer with
      poor sleep quality and reduced quality of life. Endoscopic sinus surgery has
      demonstrated encouraging results in improving sleep function. The aim of this
      systematic review is to assess the change in sleep quality after surgery for CRS.
      Data Sources PubMed, Web of Science, EMBASE. Review Methods An electronic search
      was conducted with the keywords "sinusitis" or "rhinosinusitis" and "sleep."
      Studies were included only when adults underwent endoscopic sinus surgery and
      were evaluated pre- and postoperatively by the Epworth Sleepiness Scale (ESS),
      the Pittsburgh Sleep Quality Index (PSQI), the Apnea-Hypopnea Index (AHI), the
      sleep domain of Sino-Nasal Outcome Test-22, or the sleep domain of Rhinosinusitis
      Disability Index. Results The database search yielded 1939 studies, of which 7
      remained after dual-investigator screening. The standardized mean differences
      (95% CI) for the ESS, PSQI, and AHI were -0.94 (-1.63 to -0.26), -0.80 (-1.46 to 
      0.14), and -0.20 (-0.32 to -0.07), indicating large, moderate to large, and small
      improvements, respectively. All analyses displayed high heterogeneity ( I2 = 95%
      99%). Conclusion Sleep quality, as measured by the ESS and PSQI surveys, shows
      substantial improvement after surgery for CRS, with smaller improvement seen for
      AHI. Generalizability of our results is limited by high heterogeneity among
      studies and by broad confidence intervals that cannot exclude small to trivial
      changes. The findings of this meta-analysis provide insight into the effect of
      CRS-related endoscopic sinus surgery on sleep quality, which should guide future
      research direction and counseling of patients in the clinical setting.

PMID- 29065274
TI  - High-Quality Feedback Regarding Professionalism and Communication Skills in
      Otolaryngology Resident Education.
AB  - Objective The Accreditation Council for Graduate Medical Education (ACGME)
      requires competency-based education for residents and recommends 5 basic features
      of high-quality feedback. Our aim was to examine the incorporation of feedback in
      articles regarding professionalism and interpersonal/communication skills for
      otolaryngology residency training curriculum. Data Sources PubMed, Embase, ERIC,
      Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov . Methods We
      used studies identified during a systematic review of all indexed years through
      October 4, 2016. Results Eighteen studies were included in this review.
      Professionalism was discussed in 16, of which 15 (94%) examined aspects of
      feedback. Interpersonal/communication skills were the focus of 16 articles, of
      which 14 16 (88%) discussed aspects of feedback. Our assessment demonstrated that
      timeliness was addressed in 8 (44%) articles, specificity in 4 (22%), learner
      reaction and reflection in 4 (22%), action plans in 3 (20%), and balancing
      reinforcing/corrective feedback in 2 (13%). Two articles did not address
      feedback, and 6 did not address aspects of high-quality feedback. The ACGME
      recommended feedback systems of ADAPT (ask, discuss, ask, plan together) and R2C2
      (relationship, reactions, content, and coach) were not reported in any of the
      studies. Conclusion Feedback is an essential component of graduate medical
      education and is required by the ACGME milestones assessment system. However, the
      core feedback components recommended by the ACGME are rarely included in the
      otolaryngology resident education literature.

PMID- 29065275
TI  - Multicenter Analysis of Midterm Clinical Outcomes of Arthroscopic Labral Repair
      in the Hip: Minimum 5-Year Follow-up.
AB  - BACKGROUND: The technique of hip arthroscopic surgery is advancing and becoming
      more commonly performed. However, most current reported results are limited to
      short-term follow-up, and therefore, the durability of the procedure is largely
      unknown. PURPOSE: To perform a multicenter analysis of mid-term clinical outcomes
      of arthroscopic hip labral repair and determine the risk factors for patient
      outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS:
      Prospectively collected data of primary hip arthroscopic labral repair performed
      at 4 high-volume centers between 2008 and 2011 were reviewed retrospectively.
      Patients were assessed preoperatively and postoperatively with the visual analog
      scale (VAS), modified Harris Hip Score (mHHS), and Hip Outcome Score-Sports
      Specific Subscale (HOS-SSS) at a minimum of 5 years' follow-up. Factors including
      age, body mass index (BMI), Tonnis grade, and cartilage grade were analyzed in
      relation to outcome scores, and revision rates were determined. Failure was
      defined as subsequent ipsilateral hip surgery, including revision arthroscopic
      surgery and open hip surgery. RESULTS: A total of 303 patients (101 male, 202
      female) with a mean age of 32.0 years (range, 10.7-58.9 years) were followed for
      a mean of 5.7 years (range, 5.0-7.9 years). Patients achieved mean improvements
      in VAS of 3.5 points, mHHS of 20.1 points, and HOS-SSS of 29.3 points. Thirty
      seven patients (12.2%) underwent revision arthroscopic surgery, and 12 (4.0%)
      underwent periacetabular osteotomy, resurfacing, or total hip arthroplasty during
      the study period. Patients with a BMI >30 kg/m2 had a mean mHHS score 9.5 points
      lower and a mean HOS-SSS score 15.9 points lower than those with a BMI <=30 kg/m2
      ( P < .01). Patients aged >35 years at surgery had a mean mHHS score 4.5 points
      lower and a HOS-SSS score 6.7 points lower than those aged <=35 years ( P = .03).
      Patients with Tonnis grade 2 radiographs demonstrated a 12.5-point worse mHHS
      score ( P = .02) and a 23.0-point worse HOS-SSS score ( P < .01) when compared
      with patients with Tonnis grade 0. CONCLUSION: Patients demonstrated significant
      improvements in VAS, mHHS, and HOS-SSS scores after arthroscopic labral repair.
      However, those with Tonnis grade 2 changes preoperatively, BMI >30 kg/m2, and age
      >35 years at the time of surgery demonstrated significantly decreased mHHS and
      HOS-SSS scores at final follow-up.

PMID- 29065276
TI  - Multiple comparisons in non-inferiority trials: Reaction to recent regulatory
      guidance on multiple endpoints in clinical trials.
AB  - We consider analysis of active control, non-inferiority clinical trials with
      multiple primary endpoints for assessing efficacy of an investigational
      treatment. Many of the issues with multiple endpoints for non-inferiority trials
      are similar to issues for superiority trials, but there are important
      differences. Because non-inferiority trials typically make decisions with
      confidence interval bounds instead of p-values, care must be taken in adjusting
      for multiple hypotheses. Composite endpoints are more difficult to interpret in
      non-inferiority trials due to difficulties in indirectly comparing the
      investigational treatment to placebo on each component. Otherwise many of the
      methods used in superiority trials (including sequential testing, graphical
      procedures and gatekeeping procedures) can be applied to non-inferiority trials
      with a little additional care. We focus on the differences between non
      inferiority and superiority trials to provide guidance on application of recent
      regulatory guidance to non-inferiority trials.

PMID- 29065277
TI  - Regulatory issues with multiplicity in drug approval: Principles and
      controversies in a changing landscape.
AB  - Recently, new draft guidelines on multiplicity issues in clinical trials have
      been issued by European Medicine Agency (EMA) and Food and Drug Administration
      (FDA), respectively. Multiplicity is an issue in clinical trials, if the
      probability of a false-positive decision is increased by insufficiently
      accounting for testing multiple hypotheses. We outline the regulatory principles
      related to multiplicity issues in confirmatory clinical trials intended to
      support a marketing authorization application in the EU, describe the reasons for
      an increasing complexity regarding multiple hypotheses testing and discuss the
      specific multiplicity issues emerging within the regulatory context and being
      relevant for drug approval.

PMID- 29065278
TI  - The effects of low and moderate doses of caffeine supplementation on upper and
      lower body maximal voluntary concentric and eccentric muscle force.
AB  - Despite the growing quantity of literature exploring the effect of caffeine on
      muscular strength, there is a dearth of data that directly explores differences
      in erogenicity between upper and lower body musculature and the dose-response
      effect. The present study sought to investigate the effects of low and moderate
      doses of caffeine on the maximal voluntary strength of the elbow flexors and knee
      extensors. Ten nonspecifically strength-trained, recreationally active
      participants (aged 21 +/- 0.3 years) completed the study. Using a randomised,
      counterbalanced, and double-blind approach, isokinetic concentric and eccentric
      strength was measured at 60 and 180 degrees /s following administration of a
      placebo, 3 mg.kg-1 body mass caffeine, and 6 mg.kg-1 body mass caffeine. There
      was no effect of caffeine on the maximal voluntary concentric and eccentric
      strength of the elbow flexors, or the eccentric strength of the knee extensors.
      Both 3 and 6 mg.kg-1 body mass caffeine caused a significant increase in peak
      concentric force of the knee extensors at 180 degrees /s. No difference was
      apparent between the 2 concentrations. Only 6 mg.kg-1 body mass caused an
      increase in peak concentric force during repeated contractions. The results infer
      that the effective caffeine concentration to evoke improved muscle performance
      may be related to muscle mass and contraction type. The present work indicates
      that a relatively low dose of caffeine treatment may be effective for improving
      lower body muscular strength, but may have little benefit for the strength of
      major muscular groups of the upper body.

PMID- 29065279
TI  - Gait Retraining for the Reduction of Injury Occurrence in Novice Distance
      Runners: 1-Year Follow-up of a Randomized Controlled Trial.
AB  - BACKGROUND: The increasing popularity of distance running has been accompanied by
      an increase in running-related injuries, such that up to 85% of novice runners
      incur an injury in a given year. Previous studies have used a gait retraining
      program to successfully lower impact loading, which has been associated with many
      running ailments. However, softer footfalls may not necessarily prevent running
      injury. PURPOSE: To examine vertical loading rates before and after a gait
      retraining program and assess the effectiveness of the program in reducing the
      occurrence of running-related injury across a 12-month observation period. STUDY
      DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of
      320 novice runners from the local running club completed this study. All the
      participants underwent a baseline running biomechanics evaluation on an
      instrumented treadmill with their usual running shoes at 8 and 12 km/h.
      Participants were then randomly assigned to either the gait retraining group or
      the control group. In the gait retraining group (n = 166), participants received
      2 weeks of gait retraining with real-time visual feedback. In the control group
      (n = 154), participants received treadmill running exercise but without visual
      feedback on their performance. The training time was identical between the 2
      groups. Participants' running mechanics were reassessed after the training, and
      their 12-month posttraining injury profiles were tracked by use of an online
      surveillance platform. RESULTS: A significant reduction was found in the vertical
      loading rates at both testing speeds in the gait retraining group ( P < .001,
      Cohen's d > 0.99), whereas the loading rates were either similar or slightly
      increased in the control group after training ( P = .001 to 0.461, Cohen's d =
      0.03 to -0.14). At 12-month follow-up, the occurrence of running-related
      musculoskeletal injury was 16% and 38% in the gait retraining and control groups,
      respectively. The hazard ratio between gait retraining and control groups was
      0.38 (95% CI, 0.25-0.59), indicating a 62% lower injury risk in gait-retrained
      runners compared with controls. CONCLUSION: A 2-week gait retraining program is
      effective in lowering impact loading in novice runners. More important, the
      occurrence of injury is 62% lower after 2 weeks of running gait modification.
      Registration: HKUCTR-1996 (University of Hong Kong Clinical Trials Registry).

PMID- 29065280
TI  - The Narcissism Epidemic Is Dead; Long Live the Narcissism Epidemic.
AB  - Are recent cohorts of college students more narcissistic than their predecessors?
      To address debates about the so-called "narcissism epidemic," we used data from
      three cohorts of students (1990s: N = 1,166; 2000s: N = 33,647; 2010s: N =
      25,412) to test whether narcissism levels (overall and specific facets) have
      increased across generations. We also tested whether our measure, the
      Narcissistic Personality Inventory (NPI), showed measurement equivalence across
      the three cohorts, a critical analysis that had been overlooked in prior
      research. We found that several NPI items were not equivalent across cohorts.
      Models accounting for nonequivalence of these items indicated a small decline in
      overall narcissism levels from the 1990s to the 2010s ( d = -0.27). At the facet
      level, leadership ( d = -0.20), vanity ( d = -0.16), and entitlement ( d = -0.28)
      all showed decreases. Our results contradict the claim that recent cohorts of
      college students are more narcissistic than earlier generations of college
      students.

PMID- 29065281
TI  - Preschool Intervention Can Promote Sustained Growth in the Executive-Function
      Skills of Children Exhibiting Early Deficits.
AB  - This study examined the effects of the Head Start Research-Based, Developmentally
      Informed (REDI) preschool intervention on growth in children's executive-function
      (EF) skills from preschool through third grade. Across 25 Head Start centers,
      each of 44 classrooms was randomly assigned either to an intervention group,
      which received enhanced social-emotional and language-literacy components, or to
      a "usual-practice" control group. Four-year-old children ( N = 356; 25% African
      American, 17% Latino, 58% European American; 54% girls) were followed for 5
      years, and EF skills were assessed annually. Latent-class growth analysis
      identified high, moderate, and low developmental EF trajectories. For children
      with low EF trajectories, the intervention improved EF scores in third grade
      significantly more ( d = 0.58) than in the control group. Children who received
      the intervention also demonstrated better academic outcomes in third grade than
      children who did not. Poverty often delays EF development; enriching the Head
      Start program with an evidence-based curriculum and teaching strategies can
      reduce early deficits and thereby facilitate school success.

PMID- 29065283
TI  - The Mechanism Forming the Cell Surface of Tip-Growing Rooting Cells Is Conserved
      among Land Plants.

PMID- 29065282
TI  - Does facial attractiveness influence perception of epilepsy diagnosis? An insight
      into stigma in epilepsy.
AB  - BACKGROUND: Using a group of young healthy individuals and patients with multiple
      sclerosis (pMS), we aimed to investigate whether the physical attractiveness
      judgment affects perception of epilepsy. We tested hypothesis that subjects, in
      the absence of relevant clues, would catch upon the facial attractiveness when
      asked to speculate which person suffers epilepsy and select less attractive
      choices. METHOD: Two photo-arrays (7 photos for each gender) selected from the
      Chicago Face Database (180 neutral faces of Caucasian volunteers with unknown
      medical status) were shown to study participants. Photos were evenly distributed
      along a continuum of attractiveness that was estimated by independent raters in
      prestudy stage. In each photo-array, three photos had rating 1-3 (unattractive),
      one photo had rating 4 (neutral), and three photos had rating 5-7 (attractive).
      High-quality printed photo-arrays were presented to test subjects, and they were
      asked to select one person from each photo-array "who has epilepsy". Finally, all
      subjects were asked to complete questionnaire of self-esteem and 19-item Scale of
      stereotypes toward people with epilepsy. RESULTS: In total, 71 students of
      psychology, anthropology, or andragogy (mean age: 21.6+/-1.7years; female: 85.9%)
      and 70 pMS (mean age: 37.9+/-8years; female: 71.4%) were tested. Majority of
      students or pMS had no previous personal experience with individuals with
      epilepsy (63.4%; 47.1%, p=0.052). Male photo was selected as epileptic in the
      following proportions: students - 84.5% unattractive, 8.5% neutral, and 7%
      attractive; pMS - 62.9% unattractive, 8.6% neutral, and 28.6% attractive
      (p=0.003). Female photo was selected as epileptic in the following proportions:
      students - 38% unattractive, 52.1% neutral, and 9.9% attractive; pMS - 32.9%
      unattractive, 34.3% neutral, and 32.9% attractive (0.003). Both groups showed
      very low potential for stigmatization: significantly lower in pMS in 10 items.
      Patients with multiple sclerosis showed significantly higher self-esteem than
      students (p=0.007). CONCLUSION: Facial attractiveness influences the perception
      of diagnosis of epilepsy. Both students and pMS were less willing to attribute
      epilepsy to attractive person of both genders.

PMID- 29065284
TI  - Cuttlefish.
AB  - In this quick guide, Darmaillacq and Osorio introduce the reader to the
      fascinating biology of the cuttlefish.

PMID- 29065285
TI  - Haploid induction in plants.
AB  - Gilles et al. introduce the technique of haploid induction in plant breeding.

PMID- 29065286
TI  - Phase separation in biology.
AB  - Cells have to organize their complex biochemistry to regulate their metabolism
      and respond to changes in the environment. Traditionally, intracellular
      organization has been associated with compartments that are surrounded by lipid
      membranes. However, in recent years, phase transitions have emerged as a novel
      form of cellular organization. Phase transition is a physical process whereby a
      substance changes from one physical state to another. Examples are provided by
      the freezing of water into ice (liquid to solid) or the heating of water to
      generate water vapor (liquid to gas).

PMID- 29065287
TI  - Distinct locomotor control and awareness in awake sleepwalkers.
AB  - Sleepwalkers' complex nocturnal behaviors have inspired fictional characters from
      Shakespeare's Lady Macbeth to Polidori's Vampyre to Cesare, the homicidal
      somnambulist in The Cabinet of Dr Caligari. Yet although the underlying
      pathophysiology of sleepwalking, i.e. the partial arousal from slow-wave sleep,
      is today well-documented, the detailed sensorimotor mechanisms permitting
      locomotion and further complex behaviors to occur outside of conscious control
      remain poorly understood [1]. Further, the paroxysmal character, nocturnal
      pattern, and spontaneous onset have made it nigh on impossible to study
      somnambulism behaviorally during wakefulness. The goal-directed walking paradigm
      reported here, based on full-body motion capture and virtual reality feedback,
      directly addresses this issue and provides unique insights into the functional
      mechanisms of this common parasomnia: sleepwalkers exhibited improved movement
      automation and a stronger dissociation between locomotor control and awareness
      than matched controls when challenged with a cognitive load. Our data therefore
      suggest that behavioral markers exist in awake sleepwalkers, characterized by
      their ability to perform complex locomotor actions in the absence of full
      consciousness. Our findings are important as they firmly link sleepwalking to the
      neuroscience of motor control and motor awareness and may complement formal
      diagnosis procedures (normally requiring time, cost-intensive sleep studies and
      polysomnographic recordings).

PMID- 29065288
TI  - Ocean life breaking rules by building shells in acidic extremes.
AB  - Rising levels of carbon dioxide (CO2)from fossil fuel combustion is acidifying
      our oceans [1,2]. This acidification is expected to have negative effects on
      calcifying animals because it affects their ability to build shells [3,4].
      However, the effects of ocean acidification in natural environments, subject to
      ecological and evolutionary processes (such as predation, competition, and
      adaptation), is uncertain [5,6]. These processes may buffer, or even reverse, the
      direct, short-term effects principally measured in laboratory experiments (for
      example, [6]). Here we describe the discovery of marine snails living at a
      shallow-water CO2 vent in the southwest Pacific, an environment 30 times more
      acidic than normal seawater (Figure 1). By measuring the chemical fingerprints
      locked within the shell material, we show that these snails have a restricted
      range of movement, which suggests that they live under these conditions for their
      entire lives. The existence of these snails demonstrates that calcifying animals
      can build their shells under the acidic and corrosive conditions caused by
      extreme CO2 enrichment. This unforeseen capacity, whether driven by ecological or
      adaptive processes, is key to understanding whether calcifying life may survive a
      high-CO2 future.

PMID- 29065289
TI  - Profound reversible seasonal changes of individual skull size in a mammal.
AB  - Postnatal size changes in most vertebrates are unidirectional and finite once the
      individual reaches full size [1]. In rare cases, changes of body length may occur
      in response to harsh environmental conditions. Such reactionary changes are
      distinct from seasonal, often anticipatory morphological changes, such as the
      reversible size change of some adult bird brains [2]. A unique pattern of
      profound anatomical change known as Dehnel's phenomenon has been described for
      the body, skull and brain size of red-toothed shrews and some mustelids [3-5].
      The seasonal 20% decrease and 15% re-growth of the most common proxy, braincase
      height, were documented at population level from extracted skulls post-mortem.
      Quantifying intra-individual change had so far been methodologically prohibitive.
      Here, we followed the intra-individual change in skull size and body mass
      throughout the full cycle in wild recaptured shrews (Sorex araneus). Using X-ray
      images we showed that individuals decreased the size of their braincases in
      anticipation of winter by an average of 15.3%. Braincases then partially regrew
      in spring by 9.3%. Body mass decreased by 17.6% and then dramatically increased
      by 83.4% in spring. Thus, we demonstrate that the dramatic changes incurred by
      Dehnel's phenomenon occur in the individual's bone and other tissues.

PMID- 29065290
TI  - Olfactory Imprinting: A Worm's Memory of Things Past.
AB  - Exposure to distinct stimuli during critical periods of development can affect
      behavior long-term. A new study in Caenorhabditis elegans demonstrates that
      changes in neuronal activity of one synaptic connection following early-life
      pheromone exposure are sufficient to permanently enhance specific avoidance
      responses.

PMID- 29065291
TI  - Theta Rhythm: Temporal Glue for Episodic Memory.
AB  - The low frequency theta rhythm is thought to promote the formation of long-term
      multimodal memories in the hippocampus by orchestrating input from multiple
      cortical sources. New research has demonstrated a causal association between the
      timing of experimentally induced theta rhythms and episodic memory formation in
      humans.

PMID- 29065292
TI  - Path Integration: Combining Optic Flow with Compass Orientation.
AB  - The discovery of translational optic flow detectors in the central complex of a
      bee has inspired a new model of path integration.

PMID- 29065293
TI  - Genetics: Ancient DNA Clarifies Population Histories of the Northeastern Margin
      of North America.
AB  - A new study of ancient mitochondrial DNA from Newfoundland and Labrador indicates
      that this region at the northeastern margin of North America was populated three
      times in succession by different indigenous groups. This research helps shed
      light on the movement of populations across the continent, following the initial
      peopling of the Americas.

PMID- 29065294
TI  - Structural Biology: Probing the Origins of Chromatin.
AB  - A new study finds that archaeal histone dimers can multimerize into extended
      superhelical structures that mediate gene expression changes, providing possible
      insights into the transition to eukaryotic nucleosomes.

PMID- 29065295
TI  - Conservation Biology: A Walking Stick's Redux on Lord Howe Island.
AB  - Arguably the world's rarest insect - the Lord Howe Island 'tree lobster' - is
      being brought back from the brink. A recent study has confirmed the identity of
      this species using genomic data, which backstops its reintroduction to this World
      Heritage listed oceanic island.

PMID- 29065296
TI  - Plant Genomics: Unlocking the Genome of Wheat's Progenitor.
AB  - The genome sequence and analysis of wheat's progenitor provides a roadmap to
      enhance genomics-assisted breeding and improvement of modern wheat varieties.

PMID- 29065297
TI  - Insect Flight: Navigating with Smooth Turns and Quick Saccades.
AB  - A new study shows that flying Drosophila prefer steady turns when following
      moving panoramas, but switch overwhelmingly to quick, intermittent body saccades
      when following narrow bars. This suggests insect brains trigger distinct flight
      patterns to stabilize gaze for different tasks.

PMID- 29065298
TI  - Metabolic Regulation: A Master Role for Ribulose-1,5-Bisphosphate in One-Carbon
      Assimilation.
AB  - Engineering organisms for biotechnology applications requires knowledge of their
      essential genes and associated regulatory networks. A new study of methylotrophic
      metabolism in Methylobacterium reveals essentiality of the unregulated, off
      pathway phosphoribulokinase gene and an unexpected key regulatory role for its
      product ribulose-1,5-bisphosphate.

PMID- 29065299
TI  - Economic, Socio-Political and Environmental Risks of Road Development in the
      Tropics.
AB  - It is projected that 25 million km of new paved roads will be developed globally
      by 2050 - enough to encircle the planet more than 600 times. Roughly 90% of new
      roads will be built in developing nations, frequently in tropical and subtropical
      regions with high biodiversity and environmental values. Many developing nations
      are borrowing from international lenders or negotiating access to their natural
      resources in order to expand their transportation infrastructure. Given the
      unprecedented pace and extent of these initiatives, it is vital to thoroughly
      assess the potential consequences of large-scale road and highway projects. In
      appropriate contexts and locales, new roads can promote sizeable economic and
      social benefits. If poorly planned or implemented, however, new roads can provoke
      serious cost overruns, corruption and environmental impacts, while generating
      sparse economic benefits and intense social and political conflict. Using
      examples from developing nations, we identify risks that can hinder road projects
      in wet and dry tropical environments. Such risks, we assert, are often
      inadequately considered by project proponents, evaluators and the general public,
      creating a systematic tendency to overestimate project benefits while
      understating project risks. A more precautionary approach is needed to reduce
      risks while maximizing benefits of new road projects in the tropics.

PMID- 29065300
TI  - Keeping in Touch to Differentiate.
AB  - During zebrafish gastrulation, mesendoderm progenitor cells differentiate to
      mesoderm or endoderm cells. In this issue of Developmental Cell, Barone and
      colleagues (2017) show that the interplay between cell-cell contact duration and
      morphogen signaling can control this fate segregation, providing a new framework
      for self-organization in embryonic patterning.

PMID- 29065301
TI  - The Plk1 Piece of the Nuclear Envelope Disassembly Puzzle.
AB  - Reporting in this issue of Developmental Cell, Linder et al. (2017) and Martino
      et al. (2017) reveal in highly complementary studies that Plk1 is recruited to
      the nuclear pore complex upon mitotic entry, where it acts with Cdk1 to
      hyperphosphorylate nucleoporin interfaces to promote NPC disassembly and nuclear
      envelope breakdown.

PMID- 29065302
TI  - PLD and PA Take MT1-MMP for a Metastatic Ride.
AB  - Polarized targeting and deposition of MT1-MMP is pivotal for metastasis. In this
      issue of Developmental Cell, Wang et al. (2017) reveal that a signaling molecule
      generated by phospholipase D2 drives deposition of MT1-MMP at the site of
      invadopodia formation and is critical for metastasis in a transgenic breast
      cancer model.

PMID- 29065303
TI  - Mitotic Chromosomes: Not So Silent After All.
AB  - Mitotic chromosome condensation is believed to be incompatible with
      transcription. Palozola et al. (2017) now report in Science that a transcription
      program is maintained during mitosis and that transcriptional re-activation at
      mitotic exit is geared to support cell growth rather than cell identity.

PMID- 29065304
TI  - Segmentation Genes Enter an Excited State.
AB  - The expression of segmentation clock genes is self-oscillatory due to a delayed
      negative-feedback mechanism. Hubaud et al. (2017), reporting in Cell, now reveal
      that segmentation clock genes also exhibit properties of an excitable system,
      with Yap signaling setting the threshold for adopting an oscillatory state and
      Notch signaling triggering oscillations.

PMID- 29065307
TI  - Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear
      Envelope Breakdown in C. elegans.
AB  - In animal cells, nuclear envelope breakdown (NEBD) is required for proper
      chromosome segregation. Whereas mitotic kinases have been implicated in NEBD, how
      they coordinate their activity to trigger this event is unclear. Here, we show
      that both in human cells and Caenorhabditis elegans, the Polo-like kinase 1 (PLK
      1) is recruited to the nuclear pore complexes, just prior to NEBD, through its
      Polo-box domain (PBD). We provide evidence that PLK-1 localization to the nuclear
      envelope (NE) is required for efficient NEBD. We identify the central channel
      nucleoporins NPP-1/Nup58, NPP-4/Nup54, and NPP-11/Nup62 as the critical factors
      anchoring PLK-1 to the NE in C. elegans. In particular, NPP-1, NPP-4, and NPP-11
      primed at multiple Polo-docking sites by Cdk1 and PLK-1 itself physically
      interact with the PLK-1 PBD. We conclude that nucleoporins play an unanticipated
      regulatory role in NEBD, by recruiting PLK-1 to the NE thereby facilitating
      phosphorylation of critical downstream targets.

PMID- 29065308
TI  - The Spindle Assembly Checkpoint in Arabidopsis Is Rapidly Shut Off during Severe
      Stress.
AB  - The spindle assembly checkpoint (SAC) in animals and yeast assures equal
      segregation of chromosomes during cell division. The prevalent occurrence of
      polyploidy in flowering plants together with the observation that many plants can
      be readily forced to double their genomes by application of microtubule drugs
      raises the question of whether plants have a proper SAC. Here, we provide a
      functional framework of the core SAC proteins in Arabidopsis. We reveal that
      Arabidopsis will delay mitosis in a SAC-dependent manner if the spindle is
      perturbed. However, we also show that the molecular architecture of the SAC is
      unique in plants. Moreover, the SAC is short-lived and cannot stay active for
      more than 2 hr, after which the cell cycle is reset. This resetting opens the
      possibility for genome duplications and raises the hypothesis that a rapid
      termination of a SAC-induced mitotic arrest provides an adaptive advantage for
      plants impacting plant genome evolution.

PMID- 29065306
TI  - Mitotic Disassembly of Nuclear Pore Complexes Involves CDK1- and PLK1-Mediated
      Phosphorylation of Key Interconnecting Nucleoporins.
AB  - During interphase, the nuclear envelope (NE) serves as a selective barrier
      between cytosol and nucleoplasm. When vertebrate cells enter mitosis, the NE is
      dismantled in the process of nuclear envelope breakdown (NEBD). Disassembly of
      nuclear pore complexes (NPCs) is a key aspect of NEBD, required for NE
      permeabilization and formation of a cytoplasmic mitotic spindle. Here, we show
      that both CDK1 and polo-like kinase 1 (PLK1) support mitotic NPC disintegration
      by hyperphosphorylation of Nup98, the gatekeeper nucleoporin, and Nup53, a
      central nucleoporin linking the inner NPC scaffold to the pore membrane.
      Multisite phosphorylation of Nup53 critically contributes to its liberation from
      its partner nucleoporins, including the pore membrane protein NDC1. Initial steps
      of NPC disassembly in semi-permeabilized cells can be reconstituted by a cocktail
      of mitotic kinases including cyclinB-CDK1, NIMA, and PLK1, suggesting that the
      unzipping of nucleoporin interactions by protein phosphorylation is an important
      principle underlying mitotic NE permeabilization.

PMID- 29065305
TI  - The Origin of Animal Multicellularity and Cell Differentiation.
AB  - Over 600 million years ago, animals evolved from a unicellular or colonial
      organism whose cell(s) captured bacteria with a collar complex, a flagellum
      surrounded by a microvillar collar. Using principles from evolutionary cell
      biology, we reason that the transition to multicellularity required modification
      of pre-existing mechanisms for extracellular matrix synthesis and cytokinesis. We
      discuss two hypotheses for the origin of animal cell types: division of labor
      from ancient plurifunctional cells and conversion of temporally alternating
      phenotypes into spatially juxtaposed cell types. Mechanistic studies in diverse
      animals and their relatives promise to deepen our understanding of animal origins
      and cell biology.

PMID- 29065309
TI  - PWP1 Mediates Nutrient-Dependent Growth Control through Nucleolar Regulation of
      Ribosomal Gene Expression.
AB  - Ribosome biogenesis regulates animal growth and is controlled by nutrient
      responsive mTOR signaling. How ribosome biogenesis is regulated during the
      developmental growth of animals and how nutrient-responsive signaling adjusts
      ribosome biogenesis in this setting have remained insufficiently understood. We
      uncover PWP1 as a chromatin-associated regulator of developmental growth with a
      conserved role in RNA polymerase I (Pol I)-mediated rRNA transcription. We
      further observed that PWP1 epigenetically maintains the rDNA loci in a
      transcription-competent state. PWP1 responds to nutrition in Drosophila larvae
      via mTOR signaling through gene expression and phosphorylation, which controls
      the nucleolar localization of dPWP1. Our data further imply that dPWP1 acts
      synergistically with mTOR signaling to regulate the nucleolar localization of
      TFIIH, a known elongation factor of Pol I. Ribosome biogenesis is often
      deregulated in cancer, and we demonstrate that high PWP1 levels in human head and
      neck squamous cell carcinoma tumors are associated with poor prognosis.

PMID- 29065311
TI  - Parents' transitions into and out of work-family conflict and children's mental
      health: Longitudinal influence via family functioning.
AB  - The demands arising from the combination of work and family roles can generate
      conflicts (work-family conflicts), which have become recognized as major social
      determinants of mothers' and fathers' mental health. This raises the question of
      the potential effects on children. The current study of 2496 Australian families
      (7652 observations from children aged 4-5 up to 12-13 years) asks whether changes
      in children's mental health corresponds with changes in mothers' and fathers'
      work-family conflicts. Using longitudinal random-effect structural equation
      models, adjusting for prior child mental health, changes in work-family conflict
      were examined across four adjacent pairs of biennial data waves. Children's
      mental health deteriorated when their mother or father experienced an increase in
      work-family conflict, but improved when parents' work-family conflict reduced.
      Results held for mothers, fathers and couples, and the key pathways appear to be
      changes in children's relational environments. These results contribute new
      evidence that conflicts between the work-family interface are powerful social
      determinants of mental health which have an intergenerational reach.

PMID- 29065312
TI  - Understanding the patient experience of cost-related non-adherence to
      prescription medications through typology development and application.
AB  - Many patients report skipping doses, splitting pills, or not filling
      prescriptions due to out-of-pocket costs-a phenomenon known as cost-related non
      adherence (CRNA). This study investigated CRNA from the patient's perspective,
      and, to our knowledge, is the first study to undertake a qualitative
      investigation of CRNA specifically. We report the results from 35 semi-structured
      interviews conducted in 2014-15 with adults in four Canadian cities across two
      provinces. We used framework analysis to develop a CRNA typology to characterize
      major factors in patients' CRNA decisions. Our typology identifies four major
      components: (1) the insurance reason driving the drug cost, (2) the individual's
      overall financial flexibility, (3) the burden of drug cost on the individual's
      budget, and (4) the importance of the drug from the individual's perspective. The
      first two components set the context for CRNA and the final two components are
      the drivers for the CRNA decision. We also found four major patterns in CRNA
      experiences: (1) CRNA in individuals with low financial flexibility occurred for
      all levels of drug importance and all but the lowest level of cost burden; (2)
      CRNA for high importance drugs only occurred when the drug cost had a high burden
      on an individual's budget; (3) CRNA in individuals with more financial
      flexibility primarily occurred in drugs with medium importance but high or very
      high cost burdens; and (4) CRNA for low importance drugs occurred at almost all
      levels of drug cost burden. Our study furthers the understanding of how numerous
      factors such as income, insurance, and individual preferences combine and
      interact to influence CRNA and suggests that policy interventions must be multi
      faceted or encourage significant insurance redesign to reduce CRNA.

PMID- 29065313
TI  - Analysis of the monitoring status of residual nitrite in meat products in China
      from 2000 to 2011.
AB  - The aim of this article was to analyze the monitoring status of nitrite in meat
      products consumed from 2000 to 2011 in 24 provinces, autonomous regions or direct
      controlled municipalities in China. Statistical analyses were performed on the
      monitoring status including number, proportion, and distribution of 13,316
      samples, of which 11,320 (85%) contained up to 2808.2mg/kg nitrite and 1996 (15%)
      contained no nitrite. A total of 10,299 samples (77%) qualified for GB/T 5009.33
      2003, 2003; however, 3017 samples (23%) contained nitrite at levels higher than
      the national standard. The districts with high percentage of samples with no
      nitrite were Shanghai (49%), Beijing (47%), and Liaoning (30%). While the
      districts with high percentage of meat products containing nitrite at levels
      exceeding the national standard were Jiangxi (49%), Jiangsu (33%), Shandong (29%)
      and Sichuan (29%). Therefore, the status of residue nitrite in meat products is
      of concern.

PMID- 29065310
TI  - Gender differences in the trends and correlates of major depressive episodes
      among juvenile offenders in the United States.
AB  - PURPOSE: Although it is well-established that juvenile offenders are at an
      elevated risk for depression and that, within this group, females have the
      highest risk, little is known regarding the trends in the prevalence of
      depression among juvenile offenders in the United States. In the present study,
      we systematically examine secular trends in major depressive episodes (MDE) and
      their correlates among male and female juvenile offenders and non-offenders in
      the United States. METHODS: Data were collected between 2005 and 2014 as part of
      the National Survey on Drug Use and Health (NSDUH). The NSDUH uses multistage
      area probability sampling methods to select a representative sample of the
      civilian, non-institutionalized population in the United States. Participants
      included 171,118 youth aged 12-17 (159,449 non-offenders and 11,669 offenders).
      The primary variable of interest was self-reported past year MDE. Logistic
      regression assessed whether sociodemographic factors and psychosocial and
      behavioral correlates affected the risk of MDE. RESULTS: Between 2005 and 2014,
      the prevalence of MDE among female youth increased for both offender and non
      offender groups: from 24.4% to 33.0% for the offenders and from 12.4% to 16.7%
      for the non-offenders. No significant trend changes were observed among male
      youth. In both male and female juvenile offenders, MDEs were associated with
      increased risk of illicit drug use (males OR=1.61, 95% CI=1.18-2.18; females
      OR=1.83, 95% CI=1.45-2.31). Additional correlates include alcohol use among male
      offenders (OR=1.36, 95% CI=1.01-1.83), and binge drinking in female offenders
      (OR=1.24, 95% CI=1.02-1.49). CONCLUSIONS: The prevalence of past year major
      depressive episodes is increasing for female juvenile offenders, highlighting a
      need for improved efforts to target these populations for prevention and
      treatment.

PMID- 29065314
TI  - Differential expression of extracellular matrix and integrin genes in the
      longissimus thoracis between bulls and steers and their association with
      intramuscular fat contents.
AB  - This study was performed to compare expression of genes for extracellular matrix
      (ECM) components, ECM degrading factors, and integrin subunits in the longissimus
      thoracis (LT) between bulls and steers. Steers had lower (P<0.05) ECM component
      collagen type 1 alpha1 and collagen type 3 alpha1 mRNA levels than did bulls, but
      they had higher (P<0.05) thrombospondin 1 mRNA and protein levels. Steers had
      higher (P<0.01) matrix metalloproteinase (MMP) 9 mRNA levels than did bulls.
      Steers had higher (P<0.05) integrin alpha5 mRNA levels but lower (P<0.05)
      integrin beta6 mRNA and protein levels; however, expression levels of several
      other integrin subunits were not different between steers and bulls. MMP9 mRNA
      levels were positively correlated (P<0.05) with intramuscular fat content in bull
      group. In conclusion, these results demonstrate that castration has moderate
      effects on expression of ECM components, ECM degrading factors, and integrin
      subunit genes in the LT.

PMID- 29065315
TI  - Switching memory perspective.
AB  - The perspective in which memories were spontaneously recalled, field (original
      perspective) or observer (see oneself in the memory), was examined for both
      recent and remote memories. Recent memories were dominated by field perspective
      whilst remote memories were dominated by observer perspective. Further, field
      memories contained reliably more episodic detail than observer memories. After a
      1-week interval, the same memories were recalled again but with a switched memory
      perspective. Switching from an observer to a field perspective did not reliably
      increase the amount of episodic details in a memory. Switching from field to
      observer perspective did, however, reliably reduce the number of episodic
      details. These findings suggest that memories may be represented in long-term
      memory with a fixed perspective, either field or observer, which can be
      temporarily altered sometimes changing the nature of a memory, i.e. how much
      detail remains accessible.

PMID- 29065316
TI  - Testosterone facilitates the sense of agency.
AB  - Sense of agency (SoA) refers to feelings of being in control of one's actions.
      Evidence suggests that SoA might contribute towards higher-order feelings of
      personal control - a key attribute of powerful individuals. Whether testosterone,
      a steroid hormone linked to power in dominance hierarchies, also influences the
      SoA is not yet established. In a repeated-measures design, 26 females
      participated in a double-blind, placebo-controlled trial to test the effects of
      0.5 mg testosterone on SoA, using an implicit measure based upon perceived shifts
      in time between a voluntary action and its outcome. Illusions of control, as
      operationalized by optimism in affective forecasting, were also assessed.
      Testosterone increased action binding but there was no significant effect on tone
      binding. Affective forecasting was found to be significantly more positive on
      testosterone. SoA and optimistic expectations are basic manifestations of power
      which may contribute to feelings of infallibility often associated with dominance
      and testosterone.

PMID- 29065317
TI  - Inspired by Mary Jane? Mechanisms underlying enhanced creativity in cannabis
      users.
AB  - Previous research suggests cannabis may enhance some aspects of creativity,
      although the results remain somewhat equivocal. Moreover, it is unclear whether
      differences in cannabis users' personalities may account for any potentially
      beneficial effects of cannabis on creativity. This study was designed to examine
      whether sober cannabis users demonstrate superior self-reported and objective
      creativity test performance relative to non-users, and to determine whether any
      of the Big 5 personality domains underlie these effects. A sample of sober
      cannabis users (n=412) and non-users (n=309) completed measures of cannabis
      consumption, personality, self-reported and objective creativity. Relative to non
      users, sober cannabis users self-reported higher creativity, and performed
      significantly better on a measure of convergent thinking. Controlling for
      cannabis users' higher levels of openness to experience abolished these effects.
      Therefore, while cannabis users appear to demonstrate enhanced creativity, these
      effects are an artifact of their heightened levels of openness to experience.

PMID- 29065318
TI  - The effect of teaching based on dominant learning style on nursing students'
      academic achievement.
AB  - The recognition of learning styles and teaching based on that recognition will
      help lecturers use suitable methods of teaching. The aim of this study was to
      evaluate the effect of education based on dominant learning styles on the
      academic achievement of nursing students. The population of this quasi
      experimental research consisted of 40 third-semester nursing students. The data
      were collected by using Kolb's Learning Style questionnaire. To determine the
      dominant learning style of the students, the researchers had them take a pre
      test; then, based on the dominant learning style, the students were taught
      through group discussion. A formative exam and a summative exam were taken. The
      most and least preferred learning styles of the participants were the divergent
      style and the assimilative style respectively. Education based on learning
      styles, particularly for college students, can not only enhance students'
      academic achievement and teachers' professional satisfaction, but can help with
      training professional nurses.

PMID- 29065319
TI  - Nurses' experiences of managing patient deterioration following a post
      registration education programme: A critical incident analysis study.
AB  - The aim of this study was to explore nurses' experiences assessing and managing
      deteriorating patients in practice following completion of a relevant post
      registration education programme. Recognising the increasing acuity of ward
      patients, nurses are faced with patients who are at an increased risk of
      deterioration. Patients who are acutely ill or deteriorating often exhibit
      periods of physiological deterioration; however there is evidence illustrating
      that these clinical changes are frequently missed, misinterpreted or mismanaged
      in practice. In order to prepare nurses to competently assess and manage the
      deteriorating patient, education as a care initiative is offered to develop the
      knowledge and skills required. A qualitative study using critical incident
      analysis was conducted to acquire narrative data from nurses, describing their
      clinical practice experiences of patient deterioration. Thematic analysis was
      used to analyse the data. Findings revealed improvements in nurses' abilities to
      recognise patient deterioration, greater application of the evidence base and an
      increase in confidence and assertiveness. There was some evidence of applying the
      knowledge and skills learned, however equally some nurses indicated that they
      remained ill-prepared to apply the skills in practice.

PMID- 29065320
TI  - Perceptions of community care and placement preferences in first-year nursing
      students: A multicentre, cross-sectional study.
AB  - BACKGROUND: Despite increasing shortages of highly educated community nurses, far
      too few nursing students choose community care. This means that a strong societal
      problem is emerging that desperately needs resolution. OBJECTIVES: To acquire a
      solid understanding of the causes for the low popularity of community care by
      exploring first-year baccalaureate nursing students' perceptions of community
      care, their placement preferences, and the assumptions underlying these
      preferences. DESIGN: A quantitative cross-sectional design. SETTINGS: Six
      universities of applied sciences in the Netherlands. PARTICIPANTS: Nursing
      students in the first semester of their 4-year programme (n=1058). METHODS: Data
      were collected in September-December 2014. The students completed the 'Scale on
      Community Care Perceptions' (SCOPE), consisting of demographic data and three
      subscales measuring the affective component of community care perception,
      perceptions of a placement and a profession in community care, and students'
      current placement preferences. Descriptive statistics were used. RESULTS: For a
      practice placement, 71.2% of first-year students prefer the general hospital and
      5.4% community care, whereas 23.4% opt for another healthcare area. Students
      consider opportunities for advancement and enjoyable relationships with patients
      as most important for choosing a placement. Community care is perceived as a 'low
      status-field' with many elderly patients, where students expect to find little
      variety in caregiving and few opportunities for advancement. Students'
      perceptions of the field are at odds with things they believe to be important for
      their placement. CONCLUSION: Due to misconceptions, students perceive community
      care as offering them few challenges. Strategies to positively influence
      students' perceptions of community nursing are urgently required to halt the
      dissonance between students' preference for the hospital and society's need for
      highly educated community nurses.

PMID- 29065321
TI  - Camera pose estimation to improve accuracy and reliability of joint angles
      assessed with attitude and heading reference systems.
AB  - Joint kinematics can be assessed using orientation estimates from Attitude and
      Heading Reference Systems (AHRS). However, magnetically-perturbed environments
      affect the accuracy of the estimated orientations. This study investigates, both
      in controlled and human mobility conditions, a trial calibration technic based on
      a 2D photograph with a pose estimation algorithm to correct initial difference in
      AHRS Inertial reference frames and improve joint angle accuracy. In controlled
      conditions, two AHRS were solidly affixed onto a wooden stick and a series of
      static and dynamic trials were performed in varying environments. Mean accuracy
      of relative orientation between the two AHRS was improved from 24.4 degrees  to
      2.9 degrees  using the proposed correction method. In human conditions, AHRS were
      placed on the shank and the foot of a participant who performed repeated trials
      of straight walking and walking while turning, varying the level of magnetic
      perturbation in the starting environment and the walking speed. Mean joint
      orientation accuracy went from 6.7 degrees  to 2.8 degrees  using the correction
      algorithm. The impact of starting environment was also greatly reduced, up to a
      point where one could consider it as non-significant from a clinical point of
      view (maximum mean difference went from 8 degrees  to 0.6 degrees ). The results
      obtained demonstrate that the proposed method improves significantly the mean
      accuracy of AHRS joint orientation estimations in magnetically-perturbed
      environments and can be implemented in post processing of AHRS data collected
      during biomechanical evaluation of motion.

PMID- 29065322
TI  - Sulfonyl hydrazones derived from 3-formylchromone as non-selective inhibitors of
      MAO-A and MAO-B: Synthesis, molecular modelling and in-silico ADME evaluation.
AB  - A series of sulfonyl hydrazones derived from 3-formylchromone was synthesized and
      discovered to be effective, non-selective inhibitors of monoamine oxidases (MAO-A
      and MAO-B). The compounds are easily (synthetically) accessible in high yields,
      by simple condensation of 4-methylbenzenesulfonohydrazide with different
      (un)substituted 3-formylchromones. All compounds had IC50 values in lower micro
      molar range (IC50 = 0.33-7.14 MUM for MAO-A, and 1.12-3.56 MUM for MAO-B). The
      most active MAO-B inhibitor was N'-[(E)-(6-fluoro-4-oxo-4H-chromen-3
      yl)methylidene]-4-methylbenzenesulfonohydrazide (3e) with IC50 value of 1.12 +/-
      0.02 MUM, and N'-[(E)-(6-chloro-4-oxo-4H-chromen-3-yl)methylidene]-4
      methylbenzenesulfonohydrazide (3f) was the most active MAO-A inhibitor with IC50
      value of 0.33 +/- 0.01 MUM. From enzyme kinetic studies, the mode of inhibition
      against MAO-B was found to be competitive, whereas against MAO-A, it was found to
      be non-competitive. Molecular docking studies indicated a new binding pocket for
      non-competitive MAO-A inhibitors. The activity of these compounds is optimally
      combined with highly favorable ADME profile with predicted good oral
      bioavailability.

PMID- 29065323
TI  - Amino acids in cell wall of Gram-positive bacterium Micrococcus sp. hsn08 with
      flocculation activity on Chlorella vulgaris biomass.
AB  - The aim of this work was to investigate the flocculation mechanism by Gram
      positive bacterium, Micrococcus sp. hsn08 as a means for harvesting Chlorella
      vulgaris biomass. Bacterial cells of Micrococcus sp. hsn08 were added into algal
      culture to harvest algal cells through direct contacting with algae to form
      flocs. Viability dependence test confirmed that flocculation activity does not
      depend on live bacteria, but on part of the peptidoglycan. The further
      investigation has determined that amino acids in cell wall play an important role
      to flocculate algal cells. Positively charged calcium can combine bacterial and
      algal cells together, and form a bridge between them, thereby forming the flocs,
      suggesting that ions bridging is the main flocculation mechanism. These results
      suggest that bacterial cells of Micrococcus sp. hsn08 can be applied to harvest
      microalgae biomass with the help of amino acids in cell wall.

PMID- 29065324
TI  - Heterotrophic culture of Chlorella pyrenoidosa using sucrose as the sole carbon
      source by co-culture with immobilized yeast.
AB  - Glucose is normally used as the carbon source for heterotrophic cultivation of
      algal cells, whereas sucrose is difficult to be heterotrophicly utilized by them.
      In this study, a new co-culture system was developed through mixed culture of
      Chlorella pyrenoidosa with immobilized Saccharomyces cerevisiae in the dark to
      effectively obtain pure algal suspension using sucrose as only carbon source. In
      this system, a pure algal suspension with a concentration of 2.08g/L was
      obtained. The lipid content reached 29%, which was higher than that obtained in
      glucose contained system. In addition, the immobilized yeast beads were
      repeatedly used for at least three times. Through immobilization, the choice for
      the yeast strains that are able to hydrolyze sucrose was not limited by its
      product and pure algal suspension was efficiently obtained. This strategy may
      effectively decrease the cost of carbon source in the heterotrophic cultivation
      of microalgae.

PMID- 29065325
TI  - Novel stepwise pH control strategy to improve short chain fatty acid production
      from sludge anaerobic fermentation.
AB  - This study reports an innovative strategy known as stepwise pH fermentation,
      developed to enhance the production of short chain volatile fatty acids (SCFA)
      from waste activated sludge (WAS) anaerobic fermentation. Experimental results
      confirmed the optimal pH for WAS disruption and acidification was 11 and 9,
      respectively, and corresponding optimal time was, respectively, 5 d and 2 d. In
      this scenario, the optimal SCFA yield was 2356 mg chemical oxygen demand (COD)/L,
      which was much higher than that derived from alkaline fermentation system.
      Investigation of the mechanism indicated that pH 11 could accelerate the
      disruption of WAS and inhibit the activities of methanogens; furthermore, pH 9
      was beneficial to the activity of acid-producing bacteria, resulting in more SCFA
      production. Stepwise pH fermentation integrated with sodium chloride (NaCl)
      present in WAS had synergistic impacts on WAS anaerobic fermentation.

PMID- 29065326
TI  - Effect of ultrasound pre-treatment on the physicochemical composition of Agave
      durangensis leaves and potential enzyme production.
AB  - Approximately 1 million tons of agave plants are processed annually by the
      Mexican tequila and mezcal industry, generating vast amounts of agroindustrial
      solid waste. This type of lignocellulosic biomass is considered to be
      agroindustrial residue, which can be used to produce enzymes, giving it added
      value. However, the structure of lignocellulosic biomass makes it highly
      recalcitrant, and results in relatively low yield when used in its native form.
      The aim of this study was to investigate an effective pre-treatment method for
      the production of commercially important hydrolytic enzymes. In this work, the
      physical and chemical modification of Agave durangensis leaves was analysed using
      ultrasound and high temperature as pre-treatments, and production of enzymes was
      evaluated. The pre-treatments resulted in modification of the lignocellulosic
      structure and composition; the ultrasound pre-treatment improved the production
      of inulinase by 4 U/mg and cellulase by 0.297 U/mg, and thermal pre-treatment
      improved beta-fructofuranosidase by 30 U/mg.

PMID- 29065327
TI  - Parameter estimation of activated sludge process based on an improved cuckoo
      search algorithm.
AB  - It is essential to use appropriate values for kinetic parameters in activated
      sludge model when the model is applied for wastewater treatment processes under
      different environments. An improved cuckoo search (ICS) algorithm was proposed in
      this paper for the estimation of kinetic parameters used in Activated Sludge
      Model No. 1 (ASM1). ICS is tested for its speed and accuracy in reaching solution
      by searching global minima of six standard functions. Cyclical adjustment
      strategy was employed into the detected probability to increase searching
      ability. Meanwhile, the searching step was adaptively adjusted based on the
      optimal nest of the last generation and the current iteration numbers.
      Subsequently, ICS is used to estimate 7 sensitive parameters in ASM1 for
      practical applications. Field data are used to validate prediction accuracy of
      ASM1 with estimated parameters. Predicted results of the model are closer to the
      actual data with adjusted parameters.

PMID- 29065328
TI  - Effect of zinc ions on nutrient removal and growth of Lemna aequinoctialis from
      anaerobically digested swine wastewater.
AB  - The effect of Zn2+ on ammonium and phosphorous removal and duckweed growth was
      evaluated for treatment of anaerobically digested swine wastewater (ADSW) at
      various initial Zn2+ concentrations ranging from 1.0 to 15mg/L. Lemna
      aequinoctialis taken from a local pond was selected for the treatment, and its
      fresh weight and contents of proteins, photosynthetic pigments, and vitamin E
      were examined. Results showed that the optimal Zn2+ concentration was 5.0mg/L for
      NH3-N and TP removal, the duckweed growth, and the accumulation of proteins in
      the duckweed. A maximum content of photosynthetic pigments increased with the
      increase of initial Zn2+ concentration, and it arrived earlier for a higher
      concentration of Zn2+. Vitamin E content in the duckweed reached 4.5mg/kg at
      15mg/L Zn2+ in 12-day cultivation, which showed the potential for producing and
      harvesting a high value-added product of vitamin E by culturing duckweed in ADSW.

PMID- 29065329
TI  - Phosphorus dissolution from dewatered anaerobic sludge: Effect of pHs,
      microorganisms, and sequential extraction.
AB  - Phosphorus (P) and iron mass balance from Limassol Wastewater Treatment Plant
      showed that the major removal and accumulation occurred at the aerobic secondary
      stage and at Dewatered Anaerobic Sludge (DWAS), respectively. The purpose of this
      study was to examine various parameters that effect the P dissolution under low
      pH from DWAS. The parameters that significantly contribute to P extraction were
      the exposure to pH 2.5, the anaerobic conditions and the sequential extraction.
      The addition of chemolithotrophic acidophilic bacteria has negatively influenced
      P dissolution, whereas the addition of acidophilic Heterotrophic Iron Reducing
      (HIR) bacteria has slightly increased P dissolution but they contributed to pH
      maintenance at lower levels compared to no addition of HIR. P fractionation of
      the residual sludge after sequential extraction pointed out that the organically
      bound P was hardly dissoluted from DWAS. The residual DWAS after acid treatment
      generated around 45% less methane compared to the initial DWAS.

PMID- 29065330
TI  - Experimental conditions affecting the kinetics of aqueous HCN polymerization as
      revealed by UV-vis spectroscopy.
AB  - HCN polymerization is one of the most important and fascinating reactions in
      prebiotic chemistry, and interest in HCN polymers in the field of materials
      science is growing. However, little is known about the kinetics of the HCN
      polymerization process. In the present study, a first approach to the kinetics of
      two sets of aqueous HCN polymerizations, from NH4CN and NaCN, at middle
      temperatures between 4 and 38 degrees C, has been carried out. For each series,
      the presence of air and salts in the reaction medium has been systematically
      explored. A previous kinetic analysis was conducted during the conversion of the
      insoluble black HCN polymers obtained as gel fractions in these precipitation
      polymerizations for a reaction of one month, where a limit conversion was
      achieved at the highest polymerization temperature. The kinetic description of
      the gravimetric data for this complex system shows a clear change in the linear
      dependence with the polymerization temperature for the reaction from NH4CN,
      besides a relevant catalytic effect of ammonium, in comparison with those data
      obtained from the NaCN series. These results also demonstrated the notable
      influence of air, oxygen, and the saline medium in HCN polymer formation. Similar
      conclusions were reached when the sol fractions were monitored by UV-vis
      spectroscopy, and a Hill type correlation was used to describe the polymerization
      profiles obtained. This technique was chosen because it provides an easy, prompt
      and fast method to follow the evolution of the liquid or continuous phase of the
      process under study.

PMID- 29065331
TI  - Two novel self-assemblies of supramolecular solar cells using N-heterocyclic
      anchoring porphyrins.
AB  - Two novel N-substituted anchoring porphyrins (ZnPAtz and ZnPAim) have been
      devised and synthesized. Moreover, these two anchoring porphyrins were linked to
      the TiO2 semiconductor through carboxyl groups and then a zinc porphyrin ZnP was
      bound to the anchoring porphyrin using a zinc-to-ligand axial coordination
      approach. The different performances of these assemblies were compared with
      single anchoring porphyrin devices ZnPAtz and ZnPAim. The photoelectric
      conversion efficiency of the new supramolecular solar cells sensitized by ZnP
      ZnPAx (x=tz, im) has been improved. The ZnP-ZnPAtz-based DSSCs provided the
      highest photovoltaic efficiency (1.86%). Fundamental studies showed that
      incorporation of these assemblies promote light-harvesting efficiency.

PMID- 29065332
TI  - Structural changes of wood during hydro-thermal and thermal treatments evaluated
      through NIR spectroscopy and principal component analysis.
AB  - Spruce wood samples were subjected to different conditions of thermal and hydro
      thermal treatment by varying the temperature, relative humidity and period of
      exposure. The obtained treated samples were evaluated using near infrared
      spectroscopy (NIR), principal component analysis (PCA) and hierarchical cluster
      analysis (HCA) in order to evidence the structural changes which may occur during
      the applied treatment conditions. Following this, modification in all wood
      components were observed, modifications which were dependent on the temperature,
      amount of relative humidity and also the treatment time. Therefore, higher
      variations were evidenced for samples treated at higher temperatures and for
      longer periods. At the same time, the increase in the amount of water vapours in
      the medium induced a reduced rate of side chains and condensation reactions
      occurring in the wood structure. Further, by PCA and HCA was possible to
      discriminate the modifications in the wood samples according to treatment time
      and amount of relative humidity.

PMID- 29065333
TI  - Validated spectroscopic methods for determination of anti-histaminic drug
      azelastine in pure form: Analytical application for quality control of its
      pharmaceutical preparations.
AB  - Two simple, sensitive, rapid, validated and cost effective spectroscopic methods
      were established for quantification of antihistaminic drug azelastine (AZL) in
      bulk powder as well as in pharmaceutical dosage forms. In the first method (A)
      the absorbance difference between acidic and basic solutions was measured at
      228nm, whereas in the second investigated method (B) the binary complex formed
      between AZL and Eosin Y in acetate buffer solution (pH3) was measured at 550nm.
      Different criteria that have critical influence on the intensity of absorption
      were deeply studied and optimized so as to achieve the highest absorption. The
      proposed methods obeyed Beer's low in the concentration range of (2.0-20.0MUg.mL
      1) and (0.5-15.0MUg.mL-1) with % recovery+/-S.D. of (99.84+/-0.87), (100.02+/
      0.78) for methods (A) and (B), respectively. Furthermore, the proposed methods
      were easily applied for quality control of pharmaceutical preparations without
      any conflict with its co-formulated additives, and the analytical results were
      compatible with those obtained by the comparison one with no significant
      difference as insured by student's t-test and the variance ratio F-test.
      Validation of the proposed methods was performed according the ICH guidelines in
      terms of linearity, limit of quantification, limit of detection, accuracy,
      precision and specificity, where the analytical results were persuasive.

PMID- 29065334
TI  - Continuous erector spinae plane block provides effective perioperative analgesia
      for breast reconstruction using tissue expanders: A report of two cases.

PMID- 29065335
TI  - Bilateral ultrasound-guided erector spinae plane blocks in breast cancer and
      reconstruction surgery.

PMID- 29065336
TI  - Do safety performance functions used for predicting crash frequency vary across
      space? Applying geographically weighted regressions to account for spatial
      heterogeneity.
AB  - Safety Performance Functions (SPFs) provide a basis for identifying locations
      where countermeasures can be effective. While SPFs in the Highway Safety Manual
      (HSM) were calibrated based on data from select states, calibration factors can
      be developed to localize SPFs to other states. Calibration factors typically
      provide a coarse adjustment-time and space stationarity of associations between
      crash frequencies and various factors is still assumed, implying that the SPF
      functional form is transferable. However, with increasing availability of
      statewide geo-referenced safety data, new spatial analysis methods, and
      increasing computational power, it is possible to relax the stationarity
      assumption. Specifically, to address spatial heterogeneity in SPFs, this study
      proposes relaxing SPFs (referring to them as Localized SPFs (L-SPFs)) that can be
      developed by using sophisticated geo-spatial modeling techniques that allow
      correlates of crash frequencies to vary in space. For demonstration, a 2013 geo
      referenced freeway crash and traffic database from Virginia is used. As a
      potential methodological alternative, crash frequencies are predicted by
      estimating Geographically Weighted Negative Binomial Regressions. This model
      significantly outperforms the traditional negative binomial model in terms of
      model goodness-of-fit, providing a better and fuller understanding of spatial
      variations in modeled relationships. Our study results uncover significant
      spatial variations in parameter estimates for Annual Average Daily Traffic (AADT)
      and segment length. Ignoring such variations can result in prediction errors. The
      results indicate low transferability of a single statewide SPF highlighting the
      importance of developing L-SPFs. From a practical standpoint, L-SPFs can better
      predict crash frequencies and support prioritizing safety improvements in
      specific locations.

PMID- 29065337
TI  - Generation of two induced pluripotent stem cell (iPSC) lines from X-linked
      adrenoleukodystrophy (X-ALD) patients with adrenomyeloneuropathy (AMN).
AB  - X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder caused by a
      mutation in the ATP-binding cassette transporter subfamily D member 1 (ABCD1)
      gene. We generated two induced pluripotent stem cell (iPSC) lines from X-ALD
      patients with adrenomyeloneuropathy (AMN) by Sendai virus containing OCT4, SOX2,
      KLF4 and c-MYC. Established iPSC lines expressed various pluripotency markers,
      had differentiation potential of three germ layers in vitro, had normal karyotype
      and retained ABCD1 mutation.

PMID- 29065338
TI  - Differences in the association of inflammation and tryptophan with depressive
      symptoms between white and non-white chronic dialysis patients.
AB  - OBJECTIVE: Possibly, different biochemical parameters are involved in the
      development of depressive symptoms in white and non-white dialysis patients. We
      examined whether the association between inflammation and depressive symptoms and
      between tryptophan and depressive symptoms differs between white and non-white
      dialysis patients and whether the association between inflammation and depressive
      symptoms is mediated by tryptophan degradation along the kynurenine pathway in
      both groups. METHOD: Depressive symptoms were measured with the BDI-II. HsCRP, IL
      1beta, IL-6, IL-10, and TNFalpha and tryptophan and its degradation products
      kynurenine and 3-hydroxykynurenine were measured in 270 white and 220 non-white
      patients. RESULTS: The presence of depressive symptoms was significantly higher
      in non-white patients (51%) than in white patients (37%) (P<0.01). Among white
      patients, HsCRP was significantly associated with depressive symptoms (beta=0.6
      (95% CI: 0.1-1.2)). Among non-white patients, significant associations with
      depressive symptoms were found for both HsCRP (beta=1.0 (95% CI: 0.1-2.0)) and IL
      6 (beta=2.6 (95% CI: 0.8-4.4)). Tryptophan levels were only significantly
      associated with depressive symptoms in non-white patients (beta=-0.3 (95% CI: 
      0.4--0.1)). Tryptophan degradation along the kynurenine pathway did not mediate
      the association between inflammatory markers and depressive symptoms in either
      group. CONCLUSION: Our results indicate that for white and non-white dialysis
      patients different biochemical parameters are associated with depressive
      symptoms.

PMID- 29065339
TI  - Reduced graphene oxide/BiFeO3 nanohybrids-based signal-on photoelectrochemical
      sensing system for prostate-specific antigen detection coupling with magnetic
      microfluidic device.
AB  - A novel magnetic controlled photoelectrochemical (PEC) sensing system was
      designed for sensitive detection of prostate-specific antigen (PSA) using reduced
      graphene oxide-functionalized BiFeO3 (rGO-BiFeO3) as the photoactive material and
      target-triggered hybridization chain reaction (HCR) for signal amplification.
      Remarkably enhanced PEC performance could be obtained by using rGO-BiFeO3 as the
      photoelectrode material due to its accelerated charge transfer and improved the
      visible light absorption. Additionally, efficient and simple operation could be
      achieved by introducing magnetic controlled flow-through device. The assay mainly
      involved in anchor DNA-conjugated magnetic bead (MB-aDNA), PSA aptamer/trigger
      DNA (Apt-tDNA) and two glucose oxidase-labeled hairpins (H1-GOx and H2-GOx). Upon
      addition of target PSA, the analyte initially reacted with the aptamer to release
      the trigger DNA, which partially hybridized with the anchor DNA on the MB.
      Thereafter, the unpaired trigger DNA on the MB opened the hairpin DNA structures
      in sequence and propagated a chain reaction of hybridization events between two
      alternating hairpins to form a long nicked double-helix with numerous GOx enzymes
      on it. Subsequently, the enzymatic product (H2O2) generated and consumed the
      photo-excited electrons from rGO-BiFeO3 under visible light irradiation to
      enhance the photocurrent. Under optimal conditions, the magnetic controlled PEC
      sensing system exhibited good photocurrent responses toward target PSA within the
      linear range of 0.001 - 100ng/mL with a detection limit of 0.31pg/mL. Moreover,
      favorable selectivity, good stability and satisfactory accuracy were obtained.
      The excellent analytical performance suggested that the rGO-BiFeO3-based PEC
      sensing platform could be a promising tool for sensitive, efficient and low cost
      detection of PSA in disease diagnostics.

PMID- 29065340
TI  - Hand-in-hand RNA nanowire-based aptasensor for the detection of theophylline.
AB  - Theophylline is a popular drug for many respiratory diseases. However, certain
      toxic side effects may be developed and the narrow safety range raises the demand
      for sensitive methods to constantly monitor theophylline levels. This study
      presents an electrochemical approach towards theophylline detection based on the
      recognition by split RNA aptamers. Target induced construction of hand-in-hand
      RNA nanowire on the electrode surface could further absorb silver nanoparticles
      (Ag NPs) as electrochemical species. When theophylline is not present, RNA probes
      are stable and their conformations remain unchanged. In contrast, theophylline is
      able to trigger the hairpin opening of RNA probe and subsequent self-assembly of
      RNA nanowire, which could be captured by DNA tetrahedron on the electrode
      interface. After further decorating Ag NPs on the nanowire, silver stripping
      current is measured to reveal initial theophylline concentration. The developed
      sensing strategy shows excellent specificity and sensitivity with the limit of
      detection of 50nM. Its practical utility is demonstrated by quantitative
      determination of theophylline levels in complex biological samples.

PMID- 29065341
TI  - Bio-bar-code-based photoelectrochemical immunoassay for sensitive detection of
      prostate-specific antigen using rolling circle amplification and enzymatic
      biocatalytic precipitation.
AB  - Methods based on photoelectrochemistry have been developed for immunoassay, but
      most involve in a low sensitivity and a relatively narrow detectable range.
      Herein a new bio-bar-code-based split-type photoelectrochemical (PEC) immunoassay
      was designed for sensitive detection of prostate-specific antigen (PSA), coupling
      rolling circle amplification (RCA) with enzymatic biocatalytic precipitation. The
      bio-bar-code-based immunoreaction was carried out on monoclonal anti-PSA antibody
      (mAb1)-coated microplate using primer DNA and polyclonal anti-PSA antibody
      conjugated gold nanoparticle (pDNA-AuNP-pAb2) with a sandwich-type assay format.
      Accompanying the immunocomplex, the labeled primer DNA on gold nanoparticle
      readily triggered RCA reaction in the presence of padlock
      probe/dNTPs/ligase/polymerase. The RCA product with a long single-stranded DNA
      could cause the formation of numerous hemin/G-quadruplex-based DNAzyme
      concatamers. With the assistance of nicking endonuclease, DNAzyme concatamers
      were dissociated from gold nanoparticle, which catalyzed the precipitation of 4
      chloro-1-naphthol in the presence of H2O2 onto CdS nanorods-coated electrode (as
      the photoanode for the generated holes). The formed insoluble precipitate
      inhibited the electron transfer from the solution to CdS nanorods-modified
      electrode by using ascorbic acid as the electron donor. Under the optimum
      conditions, the photocurrent of the modified electrode decreased with the
      increasing of PSA concentration. A detectable concentration for target PSA with
      this system could be achieved as low as 1.8pgmL-1. In addition, our strategy also
      showed good reproducibility, high specificity and accuracy matched well with
      commercial PSA ELISA kits for real sample analysis. These remarkable properties
      revealed that the developed PEC immunoassay has great potential as a useful tool
      for the detection of PSA in practical application.

PMID- 29065343
TI  - Characterization of structural motifs for interactions between glycosaminoglycans
      and proteins.
AB  - Glycosaminoglycans (GAGs) are a family of linear and anionic polysaccharides that
      play essential roles in many biological and physiological processes. Interactions
      between GAGs and proteins regulate function in many proteins and are related to
      many human diseases and disorders. The structural motifs and mechanisms for
      interactions between GAGs and proteins are not fully understood. Specific
      bindings, including minor but unique sequences sporadically distributed along the
      GAG chains or variably sulfated domains interspersed by undersulfated regions,
      may be specifically recognized by defined domains of a variety of proteins.
      Understanding the molecular basis of these interactions will provide a template
      for developing novel glycotherapeutic agents. The present article reviews recent
      methodologies and progress on the characterization of structural motifs in both
      GAGs and proteins involved in GAG-protein interactions. The analytical approaches
      are categorized into three groups: affinity-based methods; molecular docking,
      nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography; and mass
      spectrometry (MS) techniques. The advantages and limitations of each category of
      methods are discussed and are based on examples of using these techniques to
      investigate binding between GAGs and proteins.

PMID- 29065342
TI  - Synthesis of LewisX-O-Core-1 threonine: A building block for O-linked LewisX
      glycopeptides.
AB  - LewisX (LeX) is a branched trisaccharide Galbeta1->4(Fucalpha1->3)GlcNAc that is
      expressed on many cell surface glycoproteins and plays critical roles in innate
      and adaptive immune responses. However, efficient synthesis of glycopeptides
      bearing LeX remains a major limitation for structure-function studies of the LeX
      determinant. Here we report a total synthesis of a LeX pentasaccharide 1 using a
      regioselective 1-benzenesulfinyl piperidine/triflic anhydride promoted [3 + 2]
      glycosylation. The presence of an Fmoc-threonine amino acid facilitates
      incorporation of the pentasaccharide in solid phase peptide synthesis, providing
      a route to diverse O-linked LeX glycopeptides. The described approach is broadly
      applicable to the synthesis of a variety of complex glycopeptides containing O
      linked LeX or sialyl LewisX (sLeX).

PMID- 29065344
TI  - Quantitative analysis of the amygdala, thalamus and hippocampus on magnetic
      resonance images in paediatric bipolar disorders and compared with the children
      of bipolar parents and healthy control.
AB  - MR imaging studies in paediatric bipolar disorder have particularly focused on
      the amygdala and hippocampus, subcortical structures, and to a lesser extent on
      the thalamus. The purpose of this study was to perform structural analysis of the
      regions of interest (ROI) associated with mood regulation. In this study 18
      children (between the ages of 12-18) were matched according to their age and sex
      and were divided into three groups. These were: a paediatric bipolar disorder
      group, risk group and a healthy control group. The structured diagnostic
      interviews were performed with children and their parents. T1 weighted MR images
      in the sagittal plane with a thickness of 1mm were taken from the subjects.
      Automatic structural brain analysis was performed, and the volume and volume
      fraction (VF) of the ROIs were obtained. Brain size in the patients with
      paediatric bipolar disorder (742.4 +/- 110.1cm3) was significantly smaller than
      the healthy control group (880.7 +/- 73.8cm3) (p<=0.05). MRI analysis between the
      paediatric bipolar disorder, risk group and healthy control group revealed no
      difference between them in terms of amygdala, thalamus or hippocampal volumes. In
      this study, there was no difference between the volumes of amygdala, thalamus or
      hippocampus.

PMID- 29065345
TI  - Myelin dynamics: protecting and shaping neuronal functions.
AB  - Myelinating glial cells are well-known to insulate axons and to speed up action
      potential propagation. Through adjustments in the axonal coverage with myelin,
      myelin sheath thickness and possibly nodal/internode length oligodendrocytes are
      involved in fine-tuning the brain's computational power throughout life. Be it
      motor skill learning or social behaviors in higher vertebrates, proper
      myelination is critical in shaping brain functions. Neurons rely on their
      myelinating partners not only for setting conduction speed, but also for
      regulating the ionic environment and fueling their energy demands with
      metabolites. Also, long-term axonal integrity and neuronal survival are
      maintained by oligodendrocytes and loss of this well-coordinated axon-glial
      interplay contributes to neuropsychiatric diseases. Better insight into how
      myelination and oligodendrocyte functions are constantly fine-tuned in the adult
      CNS, which includes sensing of neuronal activity and adjusting glial metabolic
      support, will be critical for understanding higher brain functions and cognitive
      decline associated with myelin abnormalities in the aging brain.

PMID- 29065346
TI  - Sector-scanning 3D ultrasound imaging in frequency domain with 1D array
      transducer.
AB  - Sector-scanning is a conventional scanning mode in ultrasound imaging, which can
      increase the area to observe. In three-dimensional (3D) ultrasound, freehand
      imaging system is usually used. This method uses a moving elevation focused one
      dimensional (1D) transducer to construct a series of B-mode slice images, and
      then these B-mode slice images are combined to form a 3D volume image. When
      sector-scanning is used to acquire the B-mode slices, the elevation resolution is
      poor because of the elevation resolution of the probe and the interpolations
      between the slices. In this paper, based on the linear scanning method in our
      previous work, a sector-scanning 3D imaging method is proposed. In this imaging
      method, a linear array transducer without elevation focusing is also used, and
      the 1D transducer transmits limited diffraction beams and receives echo signals
      repeatedly when rotated around an axis parallel to the transducer. After
      finishing the scanning, all the received signals are combined to construct the 3D
      image in frequency domain with Fourier transform. Simulation results show that
      the new method can construct the 3D image effectively. Compared with the imaging
      method based on B-mode slices, the new method can improve the elevation
      resolution significantly. The elevation resolution can be promoted to less than 2
      mm with the imaging depth 100 mm by one transmission at each position. Besides,
      because only one transmission is needed at each position, the frame rate can be
      increased to some extent.

PMID- 29065347
TI  - Focusing phenomenon based on the coupling effect of acoustic waveguide.
AB  - We investigated the coupling effect in a pair of parallel acoustic cladded
      waveguides and extended the effect to obtain energy focusing in a specially
      structured waveguide of nested pipes. For the structure composed of two parallel
      waveguides, we simulated and verified that when an acoustic input wave propagates
      in one waveguide, the wave couples with the other and alternates between the two
      parallel waveguides with periodic amplitude and a well-defined coupling length.
      This length is related to the frequency of the input wave and the structure of
      the waveguide. Moreover, we fabricated a specially structured waveguide composed
      of four concentric circular pipes. In both simulations and experiments, we
      further demonstrated that the acoustic wave transmitted through designated ports
      of this fabricated waveguide structure can be focused onto the central waveguide
      with a well-defined focusing length, and that the focusing length is related to
      the wave frequency. Similar to its optics counterpart, not only can the coupling
      effect between the acoustic cladded waveguides be used in energy focusing in the
      nested waveguide structure, but it can also be used in other acoustic wave
      controlling devices, such as the frequency-selective device, the power switch for
      an acoustic wave, and the highly efficient pure-mode transducer.

PMID- 29065348
TI  - Subacromial impingement syndrome - What does this mean to and for the patient? A
      qualitative study.
AB  - BACKGROUND: Structured exercise has been reported as the current treatment of
      choice for patients diagnosed with subacromial impingement syndrome (SIS).
      However, it has been suggested that this diagnostic term and the language used to
      explain this condition might negatively influence patient expectations and serve
      as a barrier to engagement with exercise, hence compromising clinical outcomes.
      AIM: To explore how patients rationalise their shoulder pain following a
      diagnosis of SIS and how this understanding might impact on their perception of
      physiotherapy and engagement with exercise. DESIGN: A qualitative study using
      semi-structured interviews and analysed using the Framework method. SETTING: One
      NHS Physiotherapy department in South Yorkshire, England. PARTICIPANTS: Nine
      patients diagnosed with SIS were purposively sampled from those referred to the
      outpatient physiotherapy department by the orthopaedic team (consultant surgeons
      and registrars). RESULTS: Three main themes were generated: (1) The diagnostic
      experience, (2) Understanding of the problem, (3) Expectation of the treatment
      required; with one subtheme: (3b) Barriers to engagement with physiotherapy.
      CONCLUSION: The findings from this study suggest that diagnosis of shoulder pain
      remains grounded in a biomedical model. Understanding and explaining pain using
      the subacromial impingement model seems acceptable to patients but might have
      significant implications for engagement with and success of physiotherapy. It is
      suggested that clinicians should be mindful of the terminology they use and
      consider its impact on the patient's treatment pathway with the aim of doing no
      harm with the language used.

PMID- 29065349
TI  - Assessing muscle compliance in stroke with the Myotonometer.
AB  - BACKGROUND: This study explores changes of the intrinsic biomechanical property
      in the biceps brachii muscle after a hemispheric stroke using the Myotonometry
      technique. METHODS: Nineteen subjects with chronic hemiplegia participated in the
      study. Myotonometer was used to measure tissue displacement when compression
      force was applied at 8 levels from 2.45N to 19.6N. Muscle displacement and
      compliance were determined and averaged over multiple trials. FINDINGS:
      Statistical analysis indicated a significant decrease in muscle displacement and
      compliance in the spastic muscles compared with the contralateral side (muscle
      displacements: spastic: 4.51 (0.31) mm, contralateral: 5.74 (0.37) mm, p<0.005;
      compliance: spastic: 0.17 (0.011) mm/N, contralateral: 0.22 (0.014) mm/N,
      p<0.005). Correlation analysis, however, did not show any association between
      clinical assessments and myotonometric measurement (p>0.1). INTERPRETATION:
      Alterations of muscle compliance in the spastic side reflect changes in the
      contractile or intrinsic mechanical properties after a stroke. Findings of the
      study have demonstrated high sensitivity and effectiveness of the Myotonometer in
      assessing muscle compliance changes.

PMID- 29065350
TI  - Which one is a better predictor of ICU mortality in septic patients? Comparison
      between serial serum lactate concentrations and its removal rate.
AB  - PURPOSE: To predict 28-day mortality with serum lactate and oxygenation profile
      in sepsis. METHODS: 82 patients were admitted to the ICU with sepsis. Comorbid
      disease, hemodynamic and oxygenation parameters were recorded. Serum lactate was
      measured at T0, T6, T12 and T24 hours of admission. Arterial and venous oxygen
      saturation levels were also measured. Regression and ROC analyses were used to
      predict death within 28days. RESULTS: Out of 82 patients, 32 died within 28days
      of ICU admission. Non-survivors differed from survivors in having higher serum
      lactate concentrations on admission (0.6mmol/L; P=0.033), requiring more
      norepinephrine (14MUg/min; P<0.001), higher frequency of acute kidney injury,
      prolonged mechanical ventilation (5-days; P<0.001) and ICU stay (1-day; P=0.029).
      Saturation of oxygen in arterial (a), central venous blood (cv) and (a-cv) were
      similar between the survivors and non-survivors. T24 level of lactate was the
      best predictor of 28-day mortality with 78% sensitivity and 90% specificity
      (AUC=0.912+/-0.033). CONCLUSION: Serial measurements of serum lactate with
      special emphasis on its concentration at 24hour after admission remains the most
      predictive of short-term mortality in the ICU. Other predictors of mortality are
      relatively inferior and must be used collectively in context to better predict
      the clinical outcome of sepsis.

PMID- 29065351
TI  - End-organ recovery post-ventricular assist device can prognosticate survival.
AB  - BACKGROUND: This study examines our institutional ventricular assist devices
      (VADs) experience over two decades to understand trends towards predictors of
      mortality. METHODS: Retrospective study of patients aged 0-21years supported with
      a VAD from January 1996 to May 2015. Patient data was examined pre and post-VAD
      implant among survivors and non-survivors. RESULTS: Thirty-six patients
      identified (8 supported by Thoratec(r) VAD and 28 supported by EXCOR Berlin
      Heart(r)). Patient's diagnosis included dilated cardiomyopathy (DCM) (n=19,53%),
      congenital heart disease (CHD) (n=12,33%), and other (n=5,14%). Median age and
      body surface area (BSA) were 1.0years[0-7years] and 0.41[0.24-0.92],
      respectively. Survival to discharge was 75% with no deaths with DCM. The survival
      rate for patients with CHD was 42%. Univariate analysis showed diagnosis of CHD,
      smaller BSA and respiratory failure post-implant (Intermacs criteria) as risk
      factors for mortality. Median duration of VAD support was lower in non-survivors,
      14 vs 63days (p=0.03). Renal function at time of transplant or death was
      normal/pRIFLE Risk category in 20(74%) of survivors and 2(22%) of non-survivors
      (p=0.06). Post-implant, peak total bilirubin in the first week trended lower in
      survivors (p=0.06). CONCLUSIONS: Persistent end-organ impairment in the first
      2weeks after VAD placement could be a useful prognostic marker for survival to
      transplant.

PMID- 29065352
TI  - Sequence analysis of malacoherpesvirus proteins: Pan-herpesvirus capsid module
      and replication enzymes with an ancient connection to "Megavirales".
AB  - The order Herpesvirales includes animal viruses with large double-strand DNA
      genomes replicating in the nucleus. The main capsid protein in the best-studied
      family Herpesviridae contains a domain with HK97-like fold related to
      bacteriophage head proteins, and several virion maturation factors are also
      homologous between phages and herpesviruses. The origin of herpesvirus DNA
      replication proteins is less well understood. While analyzing the genomes of
      herpesviruses in the family Malacohepresviridae, we identified nearly 30 families
      of proteins conserved in other herpesviruses, including several phage-related
      domains in morphogenetic proteins. Herpesvirus DNA replication factors have
      complex evolutionary history: some are related to cellular proteins, but others
      are closer to homologs from large nucleocytoplasmic DNA viruses. Phylogenetic
      analyses suggest that the core replication machinery of herpesviruses may have
      been recruited from the same pool as in the case of other large DNA viruses of
      eukaryotes.

PMID- 29065353
TI  - Ancient wheat species and human health: Biochemical and clinical implications.
AB  - Wheat is the major staple food in many diets. Based on the increase in worldwide
      mortality attributable to diet-related chronic diseases, there is an increasing
      interest in identifying wheat species with greater health potential, more
      specifically for improved anti-oxidant and anti-inflammatory properties. In
      particular, ancient varieties (defined as those species that have remained
      unchanged over the last hundred years) are gaining interest since several studies
      suggested that they present a healthier nutritional profile than modern wheats.
      This manuscript reviews the nutritional value and health benefits of ancient
      wheats varieties, providing a summary of all in vitro, ex vivo, animal and human
      studies that have thus far been published. Differences in chemical composition,
      and biochemical and clinical implications of emmer, einkorn, spelt, khorasan and
      various regional Italian varieties are discussed. Although many studies based on
      in vitro analyses of grain components provide support to the premise of a
      healthier nutritional and functional potential of ancient wheat, other in vitro
      studies performed are not in support of an improved potential of ancient
      varieties. In the light of existing evidence derived from in vivo experiments,
      the ancient wheat varieties have shown convincing beneficial effects on various
      parameters linked to cardio-metabolic diseases such as lipid and glycaemic
      profiles, as well as the inflammatory and oxidative status. However, given the
      limited number of human trials, it is not possible to definitively conclude that
      ancient wheat varieties are superior to all modern counterparts in reducing
      chronic disease risk.

PMID- 29065354
TI  - Fukushima-derived radiocesium fallout in Hawaiian soils.
AB  - Several reactors at the Fukushima Dai-ichi Nuclear Power Plant suffered damage on
      March 11, 2011, resulting in the release of radiocesium (134Cs and 137Cs), as
      well as other radionuclides, into the atmosphere. A week later, these isotopes
      were detected in aerosols over the state of Hawai'i and in milk samples analyzed
      on the island of Hawai'i. This study estimated the magnitude of cesium deposition
      in soil, collected in 2015-2016, resulting from atmospheric fallout. It also
      examined the patterns of cesium wet deposition with precipitation observed on
      O'ahu and the island of Hawai'i following the disaster. Fukushima-derived fallout
      was differentiated from historic nuclear weapons testing fallout by the presence
      of 134Cs and the assumption that the 134Cs to 137Cs ratio was 1:1. Detectable,
      Fukushima-derived 134Cs inventories ranged from 30 to 630 Bq m-2 and 137Cs
      inventories ranged from 20 to 2200 Bq m-2. Fukushima-derived cesium inventories
      in soils were related to precipitation gradients, particularly in areas where
      rainfall exceeded 200 mm between March 19 and April 4, 2011. This research
      confirmed and quantified the presence of Fukushima-derived fallout in the state
      of Hawai'i in amounts higher than predicted by models and observed in the United
      States mainland, however the activities detected were an order of magnitude lower
      than fallout associated with historic sources such as the nuclear weapons testing
      in the Pacific. In addition, this study showed that areas of highest cesium
      deposition do not overlap with densely populated or agriculturally used areas.

PMID- 29065355
TI  - Study of soil-fern transfer of naturally occurring alpha emitting radionuclides
      in the Southern Region of Cameroon.
AB  - This study was carried out in the localities Melondo and Ngombas located in the
      Southern Region of Cameroon where there are known to be uranium-bearing and high
      background radiation areas. Activity concentrations of naturally occurring
      radionuclides 210Po, 238U, 235U, 234U, 232Th, 230Th, 228Th and 226Ra were
      determined in soil and fern (filicophyta) samples collected at 10 points in both
      localities. In soil, the average values of these activity concentrations (in
      Bq.kg-1 d.w.) were 210Po(130 +/- 10), 238U(126 +/- 11.6), 235U(5 +/- 1), 234U(131
      +/- 10), 232Th(400 +/- 22), 230Th(145 +/- 11), 228Th(381 +/- 21) and 226Ra(154 +/
      28) at Melondo; and 210Po(228 +/- 1), 238U(170 +/- 11), 235U(9 +/- 2), 234U(179
      +/- 12), 232Th(200 +/- 18), 230Th(184 +/- 18), 228Th(228 +/- 22) and 226Ra(416 +/
      7) at Ngomba. In fern the average activity concentrations were: 210Po(35 +/- 3),
      238U(0.68 +/- 0.05), 235U(0.042 +/- 0.01), 234U(0.90 +/- 0.05), 232Th(1.2 +/-
      0.2), 230Th(0.7 +/- 0.1), 228Th(39 +/- 3) and 226Ra(14 +/- 3) at Melondo and
      210Po(24 +/- 2), 238U(0.82 +/- 0.06), 235U(0.046 +/- 0.01), 234U(0.92 +/- 0.06),
      232Th(0.8 +/- 0.2), 230Th(0.9 +/- 0.2), 228Th(15 +/- 5) and 226Ra(14 +/- 3) at
      Ngomba. The soil-fern transfer factors (TF) (in kg.kg-1) were respectively
      210Po(1.64 * 10-1), 238U (5 * 10-3), 235U(7 * 10-3), 234U(6 * 10-3), 232Th(3 * 10
      3), 230Th(5 * 10-3), 228Th(7.9 * 10-2), and 226Ra(5.1 * 10-2). The highest TF for
      fern was for 210Po, probably because of atmospheric deposition. The TFs of
      uranium and thorium were comparable to those given in the IAEA handbook for
      grass.

PMID- 29065356
TI  - Bypassing CFTR dysfunction in cystic fibrosis with alternative pathways for anion
      transport.
AB  - One therapeutic strategy for cystic fibrosis (CF) seeks to restore anion
      transport to affected epithelia by targeting other apical membrane Cl- channels
      to bypass dysfunction of the cystic fibrosis transmembrane conductance regulator
      (CFTR) Cl- channel. The properties and regulation of the Ca2+-activated Cl-
      channel TMEM16A argue that long-acting small molecules which target directly
      TMEM16A are required to overcome CFTR loss. Through genetic studies of lung
      diseases, SLC26A9, a member of the solute carrier 26 family of anion
      transporters, has emerged as a promising target to bypass CFTR dysfunction. An
      alternative strategy to circumvent CFTR dysfunction is to deliver to CF epithelia
      artificial anion transporters that shuttle Cl- across the apical membrane.
      Recently, powerful, non-toxic, biologically-active artificial anion transporters
      have emerged.

PMID- 29065357
TI  - Determinants of compulsive buying behavior among young adults: The mediating role
      of materialism.
AB  - This research seeks to determine what makes young adults materialistic. The study
      examines the mediating role of materialism between the contextual factors and
      compulsive buying. Data was gathered from 219 Pakistani undergraduate university
      students. Partial Least Square (PLS) technique was used to analyze the data. The
      study confirms the intuition that more materialistic young adults are more likely
      to be involved in compulsive buying than are less materialistic young adults. The
      results were similar with the previous literature conducted in the western
      culture, indicating that also applies in a modern Islamic society. The findings
      of the study reveal that materialism mediated the relationship between certain
      sociological factors (i.e., group, media Celebrity endorsement, and TV
      advertisement) and compulsive buying. The study highlights the importance of
      understanding young adults' materialistic attitudes and consumption decisions and
      provides key knowledge for researchers, policymakers, and managers of leading
      brands.

PMID- 29065358
TI  - Response surface optimization, kinetic and thermodynamic studies for effective
      removal of rhodamine B by magnetic AC/CeO2 nanocomposite.
AB  - The activated carbon (AC) was obtained from waste scrap tires and modified by
      bimetallic Fe and Ce nanoparticles in order to combine both the high surface area
      and the active sites for enhanced adsorption of the dye. The produced
      nanocomposite was used as a novel cost-effective magnetic in rhodamine B (RhB)
      removal from aqueous solutions. The FT-IR, SEM, EDX, TEM, and surface area
      analysis methods were implemented to characterize the morphological, chemical,
      thermal and surface properties of the developed adsorbent. The optimum batch
      experimental conditions were found under the response surface methodology. The
      adsorption equilibrium data were well fitted by the Langmuir isotherm model. The
      adsorption capacity was 324.6 mg g-1. The kinetic and thermodynamics studies were
      also carried out to understand the adsorption mechanism. The study indicated that
      RhB adsorption by the AC/Fe/Ce magnetic adsorbent has an endothermic character
      and followed the pseudo-second-order kinetics model. By using ethanol solution,
      RhB was desorbed at high efficiency and the prepared material could be recycled
      for up to ten cycles. Thus, the magnetic nanocomposite is an effective and
      promising adsorbent for the cleaning treatment of RhB ions from wastewater by a
      large scale designed adsorption system.

PMID- 29065359
TI  - Modeling and optimization by particle swarm embedded neural network for
      adsorption of zinc (II) by palm kernel shell based activated carbon from aqueous
      environment.
AB  - Zn (II) is one the common pollutant among heavy metals found in industrial
      effluents. Removal of pollutant from industrial effluents can be accomplished by
      various techniques, out of which adsorption was found to be an efficient method.
      Applications of adsorption limits itself due to high cost of adsorbent. In this
      regard, a low cost adsorbent produced from palm oil kernel shell based
      agricultural waste is examined for its efficiency to remove Zn (II) from waste
      water and aqueous solution. The influence of independent process variables like
      initial concentration, pH, residence time, activated carbon (AC) dosage and
      process temperature on the removal of Zn (II) by palm kernel shell based AC from
      batch adsorption process are studied systematically. Based on the design of
      experimental matrix, 50 experimental runs are performed with each process
      variable in the experimental range. The optimal values of process variables to
      achieve maximum removal efficiency is studied using response surface methodology
      (RSM) and artificial neural network (ANN) approaches. A quadratic model, which
      consists of first order and second order degree regressive model is developed
      using the analysis of variance and RSM - CCD framework. The particle swarm
      optimization which is a meta-heuristic optimization is embedded on the ANN
      architecture to optimize the search space of neural network. The optimized
      trained neural network well depicts the testing data and validation data with R2
      equal to 0.9106 and 0.9279 respectively. The outcomes indicates that the
      superiority of ANN-PSO based model predictions over the quadratic model
      predictions provided by RSM.

PMID- 29065360
TI  - Use of multivariable and redundancy analysis to assess the behavior of metals and
      arsenic in urban soil and road dust affected by metallic mining as a base for
      risk assessment.
AB  - The vicinity of abandoned mining ponds to populated areas may suppose a high
      environmental and health risk being necessary evaluate unreclaimed ponds as
      source of metal(loid)s. In order to evaluate the behaviour of metals and arsenic
      from tailing ponds and their effects in urban areas, 10 mine wastes samples, 10
      urban soil and 10 urban road dust samples were collected from two mining
      districts (La Union and Mazarron, SE Spain). Physicochemical properties and
      total, available and water-soluble concentration of metals (Cd, Co, Cr, Cu, Fe,
      Ni, Mn, Pb, Zn) and As were analyzed. Results suggest enrichment in Fe, Mn, Pb
      and Zn of urban soil and road dust in both studied towns. Multivariable analysis
      indicated that Cd, Mn, Pb and Zn in La Union urban soil, and As, Cd, Cu, Pb and
      Zn in soil and Fe in road dust of Mazarron come from mining districts. In
      addition, redundancy analysis showed that mobility of metal(loid)s related to
      mining sources were more influenced by their total concentration, while metals
      with a lithogeny origin were more affected by physicochemical properties.

PMID- 29065361
TI  - Revisiting non-significant effects of intranasal oxytocin using equivalence
      testing.
AB  - The effects of intranasal oxytocin on social cognition are mixed, with several
      non-significant reports casting some doubts on its efficacy. Nevertheless,
      drawing inferences from non-significant values is problematic as non-significant
      results can be indicative of either statistical equivalence or insensitive data.
      Equivalence tests can be used to assess evidence for statistical equivalence,
      which can consequently facilitate theory falsification. To improve the inference
      of non-significant NHST p-values, this paper reports a set of equivalence tests
      performed on data from a recent meta-analysis synthesizing 32 intranasal oxytocin
      studies. Data from 26.1% of non-significant meta-analytic effects were indicative
      of data insensitivity, rather than statistical equivalence. Equivalence tests
      were also performed on a set of previously unpublished data from one laboratory,
      to examine whether unpublished data yields similar outcomes. Of the 34 non
      significant effects, 73.5% were due to data insensitivity. As these analyses
      illustrate how non-significant intranasal oxytocin results may not necessarily
      support the absence of an effect, researchers are encouraged to implement
      equivalence tests in the design of their studies. By facilitating theory
      falsification, the adoption of equivalence tests can advance the field by
      redirecting resources to more promising avenues of research.

PMID- 29065363
TI  - Hikikomori in Brazil: 29 years of Voluntary social Withdrawal.

PMID- 29065362
TI  - Pharmacological augmentation of endocannabinoid signaling reduces the
      neuroendocrine response to stress.
AB  - Activation of the hypothalamic-pituitary-adrenal axis (HPA) is critical for
      survival when the organism is exposed to a stressful stimulus. The
      endocannabinoid system (ECS) is currently considered an important neuromodulator
      involved in numerous pathophysiological processes and whose primary function is
      to maintain homeostasis. In the tissues constituting the HPA axis, all the
      components of the ECS are present and the activation of this system acts in
      parallel with changes in the activity of numerous neurotransmitters, including
      nitric oxide (NO). NO is widely distributed in the brain and adrenal glands and
      recent studies have shown that free radicals, and in particular NO, may play a
      crucial role in the regulation of stress response. Our objective was to determine
      the participation of the endocannabinoid and NOergic systems as probable
      mediators of the neuroendocrine HPA axis response to a psychophysical acute
      stress model in the adult male rat. Animals were pre-treated with cannabinoid
      receptors agonists and antagonists at central and systemic level prior to acute
      restraint exposure. We also performed in vitro studies incubating adrenal glands
      in the presence of ACTH and pharmacological compounds that modifies ECS
      components. Our results showed that the increase in corticosterone observed after
      acute restraint stress is blocked by anandamide administered at both central and
      peripheral level. At hypothalamic level both cannabinoid receptors (CB1 and CB2)
      are involved, while in the adrenal gland, anandamide has a very potent effect in
      suppressing ACTH-induced corticosterone release that is mainly mediated by
      vanilloid TRPV1 receptors. We also observed that stress significantly increased
      hypothalamic mRNA levels of CB1 as well as adrenal mRNA levels of TRPV1 receptor.
      In addition, anandamide reduced the activity of the nitric oxide synthase enzyme
      during stress, indicating that the anti-stress action of endocannabinoids may
      involve a reduction in NO production at hypothalamic and adrenal levels. In
      conclusion, an endogenous cannabinoid tone maintains the HPA axis in a stable
      basal state, which is lost with a noxious stimulus. In this case, the ECS dampens
      the response to stress allowing the recovery of homeostasis. Moreover, our work
      further contributes to in vitro evidence for a participation of the
      endocannabinoid system by inhibiting corticosterone release directly at the
      adrenal gland level.

PMID- 29065364
TI  - Effects of behavioral activation on default mode network connectivity in
      subthreshold depression: A preliminary resting-state fMRI study.
AB  - BACKGROUND: Subthreshold depression is a risk factor for major depressive
      disorder, and it is known to have a negative impact on quality of life (QOL).
      Although behavioral activation, which is one type of cognitive behavioral
      therapy, is an effective psychological intervention for subthreshold depression,
      neural mechanisms of behavioral activation are unclear. Enhanced functional
      connectivity between default mode network (DMN) and the other regions has been
      demonstrated in participants with subthreshold depression. The purpose of this
      study was to examine the effects of behavioral activation on DMN abnormalities by
      using resting-state functional MRI (rs-fMRI). METHODS: Participants with
      subthreshold depression (N =40) were randomly assigned to either an intervention
      group or a non-intervention group. They were scanned using rs-fMRI before and
      after the intervention. Independent component analysis indicated three
      subnetworks of the DMN. RESULTS: Analyzing intervention effects on functional
      connectivity of each subnetwork indicated that connectivity of the anterior DMN
      subnetwork with the dorsal anterior cingulate was reduced after the intervention.
      Moreover, this reduction was correlated with an increase in health-related QOL.
      LIMITATIONS: We did not compare the findings with healthy participants. Further
      research should be conducted by including healthy controls to verify the results
      of this study. CONCLUSIONS: Mechanisms of behavioral activation might be related
      to enhanced ability to independently use the dACC and the DMN, which increases an
      attention control to positive external stimuli. This is the first study to
      investigate neural mechanisms of behavioral activation using rs-fMRI.

PMID- 29065365
TI  - Consolidating new words from repetitive versus multiple stories: Prior knowledge
      matters.
AB  - Prior knowledge is proposed to support the consolidation of newly acquired
      material. The current study examined whether children with superior vocabulary
      knowledge show enhanced overnight consolidation, particularly when new words are
      encountered in varying stories. Children aged 10 and 11 years (N = 42) were
      exposed to two sets of eight spoken novel words (e.g., "crocodol"), with one set
      embedded in the same story presented twice and the other presented in two
      different stories. Children with superior vocabulary knowledge showed larger
      overnight gains in explicit phonological and semantic knowledge when novel words
      had been encountered in multiple stories. However, when novel words had been
      encountered in repetitive stories, existing knowledge exerted no influence on the
      consolidation of explicit phonological knowledge and had a negative impact on the
      consolidation of semantic knowledge. One full day (24 h) after story exposure,
      only very weak evidence of lexical integration (i.e., slower animacy decisions
      toward the basewords [e.g., "crocodile"] than toward the control words) was
      observed for novel words learned via repetitive (but not multiple) stories. These
      data suggest that although the consolidation of explicit new word knowledge
      learned through multiple contexts is supported by prior knowledge, lexical
      integration might benefit more from repetition.

PMID- 29065366
TI  - Social capital and oral health: The association of social capital with edentulism
      and chewing ability in the rural elderly.
AB  - OBJECTIVE: The association between social capital and oral health had been
      reported in various ways, but still remains unclear. We investigated the
      association between the social capital of the elderly living in a rural region
      and their edentulism and chewing ability. METHODS: A total of 241 elderly
      aged>=70years living in a rural city of Korea participated in this cross
      sectional study. Their social capital was surveyed by questionnaire assessing its
      network and trust dimensions. Their edentulism and chewing ability were assessed
      by oral examination and chewing gum whose color changes based on the mastication
      performance. RESULTS: The mean age of the participants was 82.7 (ranged 71 to
      101) years and 68.8% of them were female. In the binomial regression analysis,
      the general network aspect of the network dimension was significantly associated
      with chewing ability, of which the prevalence ratio was 1.88 (95% CI: 1.16-3.06)
      in the age, sex, education and marital status-adjusted model. CONCLUSION: Our
      findings suggest that social capital, such as a poor social network, is
      associated with poor chewing ability in the elderly living in rural areas.

PMID- 29065367
TI  - A healed incomplete rupture of a small artery jutting to the lateral ventricle: A
      possible cause of primary intraventricular hemorrhage.

PMID- 29065368
TI  - BBOX1 is down-regulated in maternal immune-activated mice and implicated in
      genetic susceptibility to human schizophrenia.
AB  - Prenatal exposure to infectious or inflammatory insults can increase the risk of
      developing neuropsychiatric disorders such as bipolar disorder, autism, and
      schizophrenia in later life. Gamma-butyrobetaine hydroxylase (BBOX 1) is an
      enzyme responsible for the biosynthesis of l-carnitine, a key molecule in fatty
      acid metabolism. This cytosolic dimeric protein belongs to the dioxygenase
      family. In this study, we investigated whether BBOX 1 expression was related to
      psychiatric disorder in an animal model. We also conducted a case-control study
      using 284 schizophrenia patients and 409 controls with single-nucleotide
      polymorphisms (SNPs) in the 5'-near region of BBOX 1. BBOX 1 expression was
      increased in the medial frontal cortex of a mouse model of schizophrenia induced
      by maternal immune activation. Furthermore, the genotype and allele frequencies
      of two SNPs (rs7939644 and rs10767592) were significantly associated with
      schizophrenia susceptibility. Our results suggest that BBOX 1 might be associated
      with maternal immune activation and schizophrenia susceptibility. Therefore, it
      might be involved in the pathophysiology of schizophrenia.

PMID- 29065369
TI  - The fecal microbiome of ALS patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron
      disease accompanied by both systemic and central nervous system-specific
      inflammation as well as deregulated energy metabolism. These potential
      pathogenetic factors have recently been found to mutually interact with the gut
      microbiota, raising the hypothesis of a link between microbiome alterations and
      ALS pathogenesis. The aim of our study was to assess whether ALS is associated
      with an altered composition of the fecal microbiota. We compared the fecal
      microbiota of 25 ALS patients with 32 age- and gender-matched healthy persons
      using 16S rRNA gene sequencing analysis. Confounding factors and secondary
      disease effects on the microbiome were minimized by selection of patients without
      dysphagia, gastrostomy, noninvasive ventilation, or reduced body mass index.
      Comparing the 2 carefully matched groups, the diversity and the abundance of the
      bacterial taxa on the different taxonomic levels as well as PICRUSt-predicted
      metagenomes were almost indistinguishable. Significant differences between ALS
      patients and healthy controls were only observed with regard to the overall
      number of microbial species (operational taxonomic units) and in the abundance of
      uncultured Ruminococcaceae. Conclusively, ALS patients do not exhibit a
      substantial alteration of the gut microbiota composition.

PMID- 29065371
TI  - A case-history illustrates importance of knowledge of drug-interactions when pain
      patients are prescribed non-pain drugs for co-morbidities.

PMID- 29065370
TI  - Interferon regulatory factor 6 variants affect nasolabial morphology in East
      Asian populations.
AB  - OBJECTIVE: The interferon regulatory factor 6 gene (IRF6) is one of the most
      conspicuous genes among a large number of candidate risk genes for non-syndromic
      cleft lip with or without cleft palate, which is considered to be a
      multifactorial defect. Variants of IRF6 are also suggested to affect normal
      craniofacial variations, especially in the area of the nose and the upper lip. In
      the present study, we used lateral cephalograms to establish the relationship
      between IRF6 and sagittal nasolabial morphology in healthy East Asian subjects.
      DESIGN: Genomic DNA was extracted from 215 Japanese and 226 Korean individuals,
      and genotyped for five IRF6 single nucleotide polymorphisms (SNPs): rs17389541,
      rs642961, rs2013162, rs2235371, and rs7802. These SNPs were tested by multiple
      regression analyses for their association with craniofacial measurements obtained
      from lateral cephalometrics. RESULTS: We detected a significant association
      between the derived variants, rs2013162 and rs2235371 and the distances between a
      facial bone plane indicated by distance from Nasion and Point A (NA plane) to
      soft tissue landmarks; the Subalare (NA-Sbal) and the Subnasale (NA-Sn) in the
      sagittal plane. CONCLUSION: Our results indicate that IRF6 variants play an
      important role in the normal range of variation in nasolabial soft-tissue
      morphology.

PMID- 29065372
TI  - Study of neutron fields around an intense neutron generator.
AB  - Neutron fields in the vicinity of the newly built neutron facility, at the
      University of Ontario Institute of Technology (UOIT), have been investigated in a
      series of Monte Carlo simulations and measurements. The facility hosts a P-385
      neutron generator based on a deuterium-deuterium fusion reaction. The neutron
      fluence at different locations around the neutron generator facility has been
      simulated using MCNPX 2.7E Monte Carlo particle transport program. To
      characterize neutron fields, three neutron sources were modeled with
      distributions corresponding to different incident deuteron energies of 90kV,
      110kV, and 130kV. Measurements have been carried out to determine the dose rate
      at locations adjacent to the generator using bubble detectors (BDs). The neutron
      intensity was evaluated and the total dose rates corresponding to different
      applied acceleration potentials were estimated at various locations.

PMID- 29065373
TI  - The mutual restraint effect between the expansion of Alternanthera philoxeroides
      (Mart.) Griseb and cadmium mobility in aquatic environment.
AB  - : Alternanthera philoxeroides (Mart.) Griseb is one of the most malignant weeds
      in its invision habitats. While in the cadmium-contaminated aquatic environment,
      does A. philoxeroides possess good tolerance and adaptability? To demonstrate the
      effects of cadmium on A. philoxeroides in the polluted water bodies, a hydroponic
      stress experiment was conducted over a gradient of Cd concentrations (0, 2.5 and
      5mg/l) in triplicate. The seedlings were cultured in a greenhouse and harvested
      on days 0, 10, 20, 30 and 40, respectively. The results showed the effects of
      mutual restraint between Cd and A. philoxeroides. The A. philoxeroides seedlings
      were enriched with large amounts of Cd, and the toxicity of Cd inhibited the
      rapid growth of A. philoxeroides and induced the rapid degradation of
      chlorophylls in its tissues. Furthermore, the use of iron plaque effectively
      immobilized Cd of 1123-2883mg/kg.DW on the root surface, thus it decreased the
      transferability of Cd in the aquatic environment. Due to its extensive
      adaptability, good Cd tolerance and the immobilization of Cd predominantly in the
      roots (the highest Cd concentration enriched was 7588.65+/-628.90mg/kg.DW in
      roots). A. philoxeroides effectively restrained the translocation of Cd and
      partitioned Cd in the roots within water bodies. CAPSULE: The antagonistic effect
      exists between the invasion of A. philoxeroides and cadmium mobility in aquatic
      environments.

PMID- 29065375
TI  - Cryptorchidism and increased risk of neurodevelopmental disorders.
AB  - Male congenital malformations as cryptorchidism may contribute to the development
      of neurodevelopmental disorders directly or via shared familial genetic and/or
      environmental factors, but the evidence is sparse. Using population-based health
      registries, we conducted a cohort study of all liveborn singleton boys in Denmark
      during 1979-2008. Boys with a diagnosis of cryptorchidism were categorized into
      the exposed cohort and the other boys into the unexposed comparison cohort. The
      outcomes were diagnoses of any neurodevelopmental disorders and their subtypes.
      We used Cox proportional hazards regression to compute hazard ratios (HRs),
      taking into consideration several potential confounders. Among 884,083 male
      infants, 27,505 received a diagnosis of cryptorchidism during follow-up. Boys
      with cryptorchidism were more likely to be diagnosed with intellectual disability
      (HR = 1.77; 95%confidence interval [CI]:1.59,1.97), autism spectrum disorders
      (ASD) (HR = 1.24; 95% CI:1.13,1.35), attention-deficit hyperactivity disorder
      (ADHD) (HR = 1.17; 95% CI: 1.08,1.26), anxiety (HR = 1.09; 95% CI: 1.01,1.17),
      and other behavioral/emotional disorders (HR = 1.16; 95% CI: 1.08,1.26) compared
      to boys without cryptorchidism. The observed risks of intellectual disability,
      ASD, and ADHD were increased further in boys with bilateral cryptorchidism.
      Except for anxiety, cryptorchid boys had higher risks of neurodevelopmental
      disorders than their non-cryptorchid full brothers. The observed increased risks
      were similar among boys who underwent orchiopexy, as well as among those with
      shorter waiting times for this surgery. Cryptorchidism may be associated with
      increased risks of intellectual disability, ASD, ADHD, and other
      behavioral/emotional disorders. Cryptorchidism and neurodevelopmental disorders
      may have shared genetic or in-utero/early postnatal risk factors, which need to
      be further investigated.

PMID- 29065374
TI  - Response of nematode communities to metals and PAHs in freshwater microcosms.
AB  - Freshwater microcosms were used to investigate the effects of various metals and
      polycyclic aromatic hydrocarbons (PAHs), applied as single substances and in
      mixtures, on sediment-inhabiting nematode assemblages. Several community
      measures, including nematode abundance, biomass, species richness, species
      composition and the NemaSPEAR[%]-index, were assessed and their changes in
      response to the chemical treatments were compared with the results of single
      species toxicity testing using the nematode Caenorhabditis elegans. The
      diagnostic power of endpoints revealing toxic effects was then evaluated to
      assess the general suitability of nematodes as bioindicators of sediment
      contamination by a set of relevant chemicals. Overall, community measures based
      on species-level (detected with principle response curves) responded most
      sensitively to chemical stress in the microcosms, especially in terms of biomass,
      with the C. elegans toxicity test was for the most part as sensitive to the
      chemicals as the nematode species composition. Generally, this study justified
      the suitability of nematodes in assessments of the risk of chemicals frequently
      associated with freshwater sediments and underlined the value of C. elegans in
      the prospective risk assessment of chemicals, as this species was able to
      indicate the negative effects of comparatively low sediment concentrations of the
      contaminants.

PMID- 29065376
TI  - Electronic medical record reminders and smoking cessation activities in primary
      care.
AB  - PURPOSE: The purpose of this paper is to assess electronic medical record (EMR)
      automatic reminder use in relation to smoking cessation activities among primary
      care providers. BACKGROUND: Primary-care physicians are in the frontline of
      efforts to promote smoking cessation. Moreover, doctors' prescribing privileges
      give them additional tools to help patients successfully quit smoking. New EMR
      functions can provide automated reminders for physicians to counsel smokers and
      provide prescriptions to support quit attempts. SAMPLE AND METHODS: Logit
      regression is used to analyze the 2012 National Ambulatory Medical Care Survey
      (NAMCS). Variables related to the EMR's clinical reminder capability, patient's
      smoking status, the provision of cessation counseling and the prescribing of
      drugs that support quitting are analyzed. RESULTS: For primary care visit
      documents, smoking status was recorded 77.7% of the time. Smoking cessation
      counseling was ordered/provided 16.4% of the time in physicians' offices using
      electronic reminders routinely compared to 9.1% in those lacking the
      functionality. Smoking cessation medication was ordered/prescribed for 3.7% of
      current smokers when reminders were routinely used versus 2.1% when no reminder
      was used. All the differences were statistically significant. CONCLUSIONS: The
      presence of an EMR equipped with automated clinical reminders is a valuable
      resource in efforts to promote smoking cessation. Insurers, regulators, and
      organizations promulgating clinical guidelines should include the use of EMR
      technology as part of their programs.

PMID- 29065377
TI  - Predictors of heroin abstinence in opiate substitution therapy in heroin-only
      users and dual users of heroin and crack.
AB  - AIMS: To analyse predictors of heroin abstinence in opiate substitution therapy
      (OST) based on frequency of crack use and its interactions with other predictors
      in a clinical non-experimental setting. DESIGN: Retrospective study. SETTING: A
      community drug service in London, UK. PARTICIPANTS: 325 clients starting OST
      between 2010 and 2014 (197 methadone and 128 buprenorphine). MEASUREMENTS:
      Logistic regression models (a general model and separate models for methadone and
      buprenorphine) assessed demographic and clinical data as predictors of heroin
      abstinence at one year after treatment start (or at the date of transfer to
      another service). FINDINGS: For the general model participants choosing methadone
      were more likely to use heroin at follow up (OR=2.36, 95% CI: 1.40-3.17) as were
      daily crack users on methadone (OR=2.62, 95% CI: 0.96-7.16). For the methadone
      model only daily crack use predicted heroin use at follow up (OR=2.62, 95% CI:
      0.96-7.16). For buprenorphine, higher amounts of baseline heroin use, lower
      buprenorphine dose and daily drinking predicted heroin use at follow up (OR=0.85,
      95% CI: 0.75-0.95; OR=1.31, 95% CI: 1.06-1.60 and OR=6.04, 95% CI: 1.26-28.92).
      Both use of cannabis and depression increased likelihood of heroin abstinence for
      clients not using crack compared to occasional (OR=6.68, 95% CI: 0.37-119.59;
      OR=106.31, 95% CI: 3.41-3313.30) and daily (OR=57.49 (95% CI: 2.37-1396.46;
      OR=170.99 (95% CI: 4.61-6339.47) users. CONCLUSIONS: Most of the predictors in
      the general model were found significant only in the buprenorphine but not in the
      methadone model, suggesting that a general model has little predictive value.
      Crack use was a significant predictor of heroin abstinence at follow up in all
      models, however for buprenorphine only when depression or cannabis use was
      present. Further research is needed to assess effective treatment approaches for
      the growing population of dual users.

PMID- 29065378
TI  - Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer:
      European Society of Digestive Oncology (ESDO) expert discussion and
      recommendations from the 17th European Society for Medical Oncology (ESMO)/World
      Congress on Gastrointestinal Cancer, Barcelona.
AB  - BACKGROUND AND SCOPE: In the epoch of precision medicine and personalised
      oncology, which aims to deliver the right treatment to the right patient,
      molecular genetic biomarkers are a topic of growing interest. The aim of this
      expert discussion and position paper is to review the current status of various
      molecular tests for gastrointestinal (GI) cancers and especially considering
      their significance for the clinical routine use. METHODOLOGY: Opinion leaders and
      experts from diverse nationalities selected on scientific merit were asked to
      answer to a prepared set of questions about the current status of molecular
      diagnostics in different GI cancers. All answers were then discussed during a
      plenary session and reported here in providing a well-balanced reflection of both
      clinical expertise and updated evidence-based medicine. RESULTS: Preselected
      molecular genetic biomarkers that are described and disputed in the current
      medical literature in different GI cancers were debated, and recommendations for
      clinical routine practice were made whenever possible. Furthermore, the
      preanalytical variations were commented and proposals for quality controls of
      biospecimens were made. CONCLUSION: The current article summarises the
      recommendations of the expert committee regarding prognostic and predictive
      molecular genetic biomarkers in different entities of GI cancers. The briefly and
      comprehensively formulated guidelines should assist clinicians in the process of
      decision making in daily clinical practice.

PMID- 29065380
TI  - An electron paramagnetic resonance mobile universal surface explorer.
AB  - Many samples cannot be studied by electron paramagnetic resonance (EPR)
      spectroscopy because they are too large to fit into the spectrometer and too
      precious to be destructively sampled for study. An EPR mobile universal surface
      explorer (MOUSE), also known as a unilateral EPR spectrometer, was constructed
      for studying this class of sample. The EPR MOUSE can nondestructively record a
      low frequency EPR (LFEPR) spectrum of a small region of any size object by
      placing the MOUSE against the object. The capabilities of the EPR MOUSE are
      demonstrated on paramagnetic paint pigments on canvas, magnetic ink on paper, and
      a ceramic candlestick. The mobile nature of the MOUSE will allow the spectrometer
      to be brought to the sample, thus opening new applications of EPR spectroscopy.

PMID- 29065379
TI  - Measuring the impact of global tropospheric ozone, carbon dioxide and sulfur
      dioxide concentrations on biodiversity loss.
AB  - The aim of this study is to examine the impact of air pollutants, including mono
      nitrogen oxides (NOx), nitrous oxide (N2O), sulfur dioxide (SO2), carbon dioxide
      emissions (CO2), and greenhouse gas (GHG) emissions on ecological footprint,
      habitat area, food supply, and biodiversity in a panel of thirty-four developed
      and developing countries, over the period of 1995-2014. The results reveal that
      NOx and SO2 emissions both have a negative relationship with ecological
      footprints, while N2O emission and real GDP per capita have a direct relationship
      with ecological footprints. NOx has a positive relationship with forest area, per
      capita food supply and biological diversity while CO2 emission and GHG emission
      have a negative impact on food production. N2O has a positive impact on forest
      area and biodiversity, while SO2 emissions have a negative relationship with
      them. SO2 emission has a direct relationship with per capita food production,
      while GDP per capita significantly affected per capita food production and food
      supply variability across countries. The overall results reveal that SO2, CO2,
      and GHG emissions affected potential habitat area, while SO2 and GHG emissions
      affected the biodiversity index. Trade liberalization policies considerably
      affected the potential habitat area and biological diversity in a panel of
      countries.

PMID- 29065381
TI  - Advances in transference-focused psychotherapy derived from the study of
      borderline personality disorder: clinical insights with a focus on mechanism.
AB  - The most current conceptualization of personality pathology emphasizes the
      assessment of the severity of selected domains of functioning involving lack of
      accurate perceptions of self and others that are common across the personality
      disorder categories. Advances in our understanding of personality pathology have
      stimulated further development of Transference-Focused Psychotherapy (TFP) for
      patients with borderline personality disorder, including treatment focus on both
      behavior and mental representations of self and others, the trajectory of change
      in TFP, and the extension of TFP principles to the entire domain of personality
      pathology.

PMID- 29065382
TI  - DSM models of personality disorders.
AB  - Personality disorders have been included in every edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM), published by the American
      Psychiatric Association. Diagnostic terms and revisions from the initial DSM to
      the current one (DSM-5) are described, and the continuing controversies regarding
      categorical versus dimensional models are reviewed, including a summary of the
      new Alternative Model for DSM-5 Personality Disorders, in Section III of DSM-5.

PMID- 29065384
TI  - Molecular control of regulatory T cell development and function.
AB  - Treg cells expressing the transcription factor Foxp3 are essential for
      immunological tolerance and homeostasis. Recent genome-wide studies have revealed
      that Foxp3+ natural Treg cells possess a number of unique transcriptional and
      epigenetic features, which appear to be acquired along the course of Treg cell
      development and maintained throughout their lifespan. These studies also provide
      novel insights into how genomic variations contribute to genetic susceptibility
      to human autoimmune diseases by affecting Treg cell development and function.

PMID- 29065383
TI  - Relation between polyphenols, malondialdehyde, antioxidant capacity, lactate
      dehydrogenase and toxic elements in human colostrum milk.
AB  - The present study investigated the interrelationships between the concentration
      of total polyphenols (TP), malondialdehyde (MDA), total antioxidant capacity
      (TAC), lactate dehydrogenase activity (LDH) and content of toxic elements (Al,
      As, Cd, Ni, Pb) in human colostrum milk (n = 75), and further assessed their
      potential association with maternal lifestyle characteristics. As and Cd were
      always below detection limits while Al, Ni and Pb were found at the level of
      89.7, 6.2 and 1.3 MUg L-1, respectively. Concentrations of TP and MDA, in the
      studied group were 46.91 +/- 21.25 mg GAE L-1 and 0.66 +/- 0.27 nmol mL-1,
      respectively, and were inversely correlated (Rs = -0.32; p < 0.01). TP and TAC
      increased significantly with maternal consumption of vegetables (Rs = 0.25 and Rs
      = 0.37, respectively; p < 0.05). Concentration of Al was positively correlated
      with MDA (Rs = 0.21; p < 0.01) and negatively with TP (Rs = -0.28; p < 0.01).
      Positive correlation was also found between Pb and MDA (Rs = 0.32; p < 0.01). No
      association with place of living (urban/rural), women's age and former smoking
      were found for any studied milk parameter. The results add to the general
      understanding of factors influencing redox balance in milk and potentially
      affecting its quality.

PMID- 29065386
TI  - Preparation and cold welding of silver nanowire based transparent electrodes with
      optical transmittances >90% and sheet resistances <10 ohm/sq.
AB  - In this article, silver nanowires (AgNWs) with aspect ratios of 1000 and lengths
      up to 200 MUm are obtained by a modified polyol approach. These very long AgNWs
      are then utilized to prepare transparent electrodes (TEs) displaying a
      transmittance of 91.3% at a sheet resistance of 8.6 ohm/sq without any post
      treatment. Furthermore, we also demonstrate a process for the cold welding of Ag
      NWs by simply dipping the AgNWs films into CTAB solutions, resulting in a further
      improvement for the optoelectronic performance. After the post-treatment, the
      AgNW-based TEs can achieve a transmittance of 93% at a sheet resistance of 9.5
      ohm/sq. In addition, the electric behaviors of AgNW-based TEs are investigated.
      In the bulk-like regime, for the as-prepared AgNW-based TEs, the Figure of merit
      (FOM), DC to optical conductivity ratio reaches up to 566.8. After the cold
      welding process, the DC to optical conductivity ratio can reach even higher
      values (631.6). In the percolative regime, the as-prepared and welded AgNW-based
      TEs can achieve Pi (FOM with percolative-like behavior) values of 166.8 and
      242.1, respectively.

PMID- 29065385
TI  - Insights into immune tolerance from AIRE deficiency.
AB  - AIRE is a well-established master regulator of central tolerance. It plays an
      essential role in driving expression of tissue-specific antigens in the thymus
      and shaping the development of positively selected T-cells. Humans and mice with
      compromised or absent AIRE function have markedly variable phenotypes that
      include a range of autoimmune manifestations. Recent evidence suggests that this
      variability stems from cooperation of autoimmune susceptibilities involving both
      central and peripheral tolerance checkpoints. Here we discuss the broadening
      understanding of the factors that influence Aire expression, modify AIRE
      function, and the impact and intersection of AIRE with peripheral immunity. This
      rapidly expanding body of knowledge will force a reexamination of the definition
      and clinical management of APS-1 patients as well as provide a foundation for the
      development of immunomodulatory strategies targeting central tolerance.

PMID- 29065387
TI  - Efficacious separation of electron-hole pairs in CeO2-Al2O3 nanoparticles
      embedded GO heterojunction for robust visible-light driven dye degradation.
AB  - Herein, we have developed a facile and one pot synthesis of ternary CeO2-Al2O3@GO
      nanocomposite via wet chemical method. The structural and morphological
      characteristics of the synthesized nanocomposite was investigated using UV-DRS,
      FT-IR, XRD, FE-SEM, HR-TEM, EDX and TGA analysis. The CeO2-Al2O3@GO composite was
      tested for its ability to photocatalytically degrade Rhodamine B (RhB) under
      visible light illumination. The influence of various operational parameters such
      as pH, catalyst dosage and initial dye concentration on the photo degradation was
      investigated in detail. The synthesized CeO2-Al2O3@GO composite shows greater
      photocatalytic degradation of RhB (99.0%) under visible light irradiation than
      the raw CeO2, Al2O3, and GO catalysts and any other reported nanocomposite
      materials. The recyclability results also demonstrate the excellent stability and
      reusability of the CeO2-Al2O3@GO nanocomposite. This work will be beneficial in
      the field of industrial and engineering applications in the degradation of
      organic pollutants. Also, a study of this kind will definitely stimulate many
      researches in the recently emerging field of solar-driven water splitting.

PMID- 29065388
TI  - Targeted sequencing of clade-specific markers from skin microbiomes for forensic
      human identification.
AB  - The human skin microbiome is comprised of diverse communities of bacterial,
      eukaryotic, and viral taxa and contributes millions of additional genes to the
      repertoire of human genes, affecting human metabolism and immune response.
      Numerous genetic and environmental factors influence the microbiome composition
      and as such contribute to individual-specific microbial signatures which may be
      exploited for forensic applications. Previous studies have demonstrated the
      potential to associate skin microbial profiles collected from touched items to
      their individual owner, mainly using unsupervised methods from samples collected
      over short time intervals. Those studies utilize either targeted 16S rRNA or
      shotgun metagenomic sequencing to characterize skin microbiomes; however, these
      approaches have limited species and strain resolution and susceptibility to
      stochastic effects, respectively. Clade-specific markers from the skin
      microbiome, using supervised learning, can predict individual identity using skin
      microbiomes from their respective donors with high accuracy. In this study the
      hidSkinPlex is presented, a novel targeted sequencing method using skin
      microbiome markers developed for human identification. The hidSkinPlex (comprised
      of 286 bacterial (and phage) family-, genus-, species-, and subspecies-level
      markers), initially was evaluated on three bacterial control samples represented
      in the panel (i.e., Propionibacterium acnes, Propionibacterium granulosum, and
      Rothia dentocariosa) to assess the performance of the multiplex. The hidSkinPlex
      was further evaluated for prediction purposes. The hidSkinPlex markers were used
      to attribute skin microbiomes collected from eight individuals from three body
      sites (i.e., foot (Fb), hand (Hp) and manubrium (Mb)) to their host donor.
      Supervised learning, specifically regularized multinomial logistic regression and
      1-nearest-neighbor classification were used to classify skin microbiomes to their
      hosts with up to 92% (Fb), 96% (Mb), and 100% (Hp) accuracy. All samples (n=72)
      regardless of body site origin were correctly classified with up to 94% accuracy,
      and body site origin could be predicted with up to 86% accuracy. Finally, human
      short tandem repeat and single-nucleotide polymorphism profiles were generated
      from skin swab extracts from a single subject to highlight the potential to use
      microbiome profiling in conjunction with low-biomass samples. The hidSkinPlex is
      a novel targeted enrichment approach to profile skin microbiomes for human
      forensic identification purposes and provides a method to further characterize
      the utility of skin microflora for human identification in future studies, such
      as the stability and diversity of the personal skin microbiome.

PMID- 29065389
TI  - Td4IN2: A drought-responsive durum wheat (Triticum durum Desf.) gene coding for a
      resistance like protein with serine/threonine protein kinase, nucleotide binding
      site and leucine rich domains.
AB  - Wheat, the main food source for a third of world population, appears strongly
      under threat because of predicted increasing temperatures coupled to drought.
      Plant complex molecular response to drought stress relies on the gene network
      controlling cell reactions to abiotic stress. In the natural environment, plants
      are subjected to the combination of abiotic and biotic stresses. Also the
      response of plants to biotic stress, to cope with pathogens, involves the
      activation of a molecular network. Investigations on combination of abiotic and
      biotic stresses indicate the existence of cross-talk between the two networks and
      a kind of overlapping can be hypothesized. In this work we describe the isolation
      and characterization of a drought-related durum wheat (Triticum durum Desf.)
      gene, identified in a previous study, coding for a protein combining features of
      NBS-LRR type resistance protein with a S/TPK domain, involved in drought stress
      response. This is one of the few examples reported where all three domains are
      present in a single protein and, to our knowledge, it is the first report on a
      gene specifically induced by drought stress and drought-related conditions, with
      this particular structure.

PMID- 29065390
TI  - Improving tobacco dependence treatment outcomes for smokers of lower
      socioeconomic status: A randomized clinical trial.
AB  - INTRODUCTION: Evidence-based treatments for tobacco dependence are significantly
      less effective for smokers of lower socioeconomic status which contributes to
      socioeconomic disparities in smoking prevalence rates and health. We aimed to
      reduce the socioeconomic gradient in treatment outcomes by systematically
      adapting evidence-based, cognitive-behavioral treatment for tobacco dependence
      for diverse lower socioeconomic smokers. METHODS: Participants were randomized to
      adapted or standard treatment, received six 1-h group treatment sessions, and
      were followed for six months. We examined the effectiveness of the adapted
      treatment to improve treatment outcomes for lower socioeconomic groups. RESULTS:
      Participants (n=227) were ethnically, racially, and socioeconomically diverse.
      The adapted treatment significantly reduced the days to relapse for the two
      lowest socioeconomic groups: SES1: M=76.6 (SD 72.9) vs. 38.3 (SD 60.1) days to
      relapse (RR=0.63 95% CI, 0.45, 0.88, p=0.0013); SES2: M=88.2 (SD 67.3) vs. 40.1
      (SD 62.6 days to relapse (RR=0.57 95% CI, 0.18, 0.70, p=0.0024). Interactions
      between socioeconomic status and condition were significant for initial
      abstinence (OR=1.26, 95% CI 1.09, 1.46, p=0.002), approached significance for 3
      month abstinence (OR=0.90, 95% CI 0.80, 1.01, p<0.071), and were not significant
      for 6-month abstinence (OR=0.99 95% CI 0.88, 1.10, p=0.795). No significant
      differences in long-term abstinence were observed. CONCLUSION: Systematic
      adaption of evidence-based treatment for tobacco dependence can significantly
      improve initial and short-term treatment outcomes for diverse lower socioeconomic
      smokers and reduce inequities in days to relapse. Novel methods of providing
      targeted extended support are needed to improve long-term outcomes.

PMID- 29065392
TI  - Cleavage of Ku80 by caspase-2 promotes non-homologous end joining-mediated DNA
      repair.
AB  - Non-homologous end-joining (NHEJ)-mediated repair of DNA double-strand breaks
      (DSBs) requires the formation of a Ku70/Ku80/DNA-PKcs complex at the DSB sites. A
      previous study has revealed Ku80 cleavage by caspase-3 during apoptosis. However,
      it remains largely unknown whether and how Ku80 cleavage affects its function in
      mediating NHEJ-mediated DNA repair. Here we report that Ku80 can be cleaved by
      caspases-2 at D726 upon a transient etoposide treatment. Caspase-2-mediated Ku80
      cleavage promotes Ku80/DNA-PKcs interaction as the D726A mutation diminished Ku80
      interaction with DNA-PKcs, while a Ku80 truncate (Ku80 DeltaC6) lacking all the 6
      residues following D726 rescued the weakened Ku80/DNA-PKcs interaction caused by
      caspase-2 knockdown. As a result, depletion or inhibition of caspase-2 impairs
      NHEJ-mediated DNA repair, and such impairment can be reversed by Ku80 DeltaC6
      overexpression. Taken together, our current study provides a novel mechanism for
      regulating NHEJ-mediated DNA repair, and sheds light on the function of caspase-2
      in genomic stability maintenance.

PMID- 29065391
TI  - Rural and urban comparisons of polysubstance use profiles and associated
      injection behaviors among people who inject drugs in Puerto Rico.
AB  - INTRODUCTION: In contrast to urban populations, little is known about
      polysubstance use among rural people who inject drugs (PWID), particularly in
      Puerto Rico where injection drug use and related health consequences are
      prevalent. The aim of the study is to compare injection and non-injection
      substance use profiles among separate urban and rural samples of Puerto Rican
      PWID. MATERIAL AND METHODS: Data for the urban sample come from 455 PWID who
      participated in the CDC's National HIV Behavioral Surveillance survey of
      injection drug use in San Juan. The data for the rural sample come from 315 PWID
      residing in four rural cities approximately 40-miles from San Juan. Latent class
      analysis was used to derive separate urban and rural profiles of weekly injection
      and non-injection substance use. Injection behaviors were examined as possible
      correlates of latent class membership. RESULTS: Five latent classes were
      identified in the urban sample, and three latent classes were identified in the
      rural sample. Classes were similar across samples; however, key differences
      emerged. Both samples had classes of primary heroin injectors, primary speedball
      injectors, and cocaine-heroin injectors. The urban sample had one high
      polysubstance class. Polysubstance use profiles that shared similar
      characteristics between samples also shared similar injection patterns, with some
      variation. DISCUSSION: Variations in substance use patterns and associated health
      risks are likely shaped by social and geographic boundaries. CONCLUSIONS:
      Understanding variations in substance use patterns across rural and urban locales
      may improve surveillance efforts and tailor desistance and harm reduction efforts
      at the state and local levels.

PMID- 29065393
TI  - Electronic structure, vibrational assignments and simulation studies with A/T
      rich DNA duplex of an aromatic bis-amidine derivative.
AB  - In this paper, computational investigations have been carried out on an aromatic
      bis-amidine which is considered to be crucial due to its peculiar properties
      including anti-Pneumocystis carinii pneumonia(PCP), anti-inflammatory and
      anticancer activities. The raw structure of an aromatic bis-amidine namely; 2,5
      bis[4-(N-cyclohexyl-amidino)phenyl]furan was retrieved, optimized and geometrical
      parameters were computed. The computational results have been compared with those
      of reported experimental values. In order to check its binding capability, we
      pave the way a step further by the interaction of the molecule with DNA duplex,
      5'(CGCGAATTCGCG)3', which consisted of A/T base pairs in its central region. In
      addition to geometrical, MEP, HOMO-LUMO analyses and IR assignments, molecular
      docking with DNA has also been performed. The best docked complex was subjected
      to molecular dynamics simulation for 50ns using AMBER force field. Free energy of
      binding has been calculated using MM/PBSA method. The outcomes demonstrate that
      the molecule recognizes both the strands of DNA duplex through hydrogen bonding
      within the minor groove side, preferably at A/T rich region and remains stable
      during the course of dynamics. It may be concluded that the compound shows better
      binding capability with duplex under study and may be used as a drug lead against
      Pneumocystis carinii pneumonia.

PMID- 29065394
TI  - Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the
      PI3K/Akt Signaling Pathway in Rats with Glaucoma.
AB  - BACKGROUND/AIMS: The aim of the present study is to investigate the effect of
      long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC)
      apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma.
      METHODS: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy
      1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression
      vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference
      (RNAi), and control vector MALAT1-negative control (NC) were constructed. A
      chronic high intraocular pressure (IOP) rat model of glaucoma was established by
      episcleral vein cauterization. The RGCs were divided into the RGC control, RGC
      pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure +
      MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the
      normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP +
      MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the
      expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect
      RGC apoptosis. RESULTS: Immunocytochemistry revealed that the cultured RGCs
      reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC
      pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1,
      lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while
      these expression levels were reversed in the RGC pressure + MALAT1-RNAi group.
      RGC numbers and PI3K/Akt expression levels in the high IOP model groups were
      lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the
      mRNA and protein expression levels of PI3K/Akt were reduced but higher than those
      in the other three high IOP model groups. Additionally, RGC numbers in the high
      IOP + MALAT1-RNAa group were lower than those in the normal group but higher than
      those in the other three high IOP model groups. CONCLUSION: Our study provides
      evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through
      activation of the PI3K/Akt signaling pathway.

PMID- 29065395
TI  - Life-Threatening Atypical Case of Acute Generalized Exanthematous Pustulosis.
AB  - Antibiotics are known to cause severe cutaneous adverse reactions, such as the
      rare acute generalized exanthematous pustulosis (AGEP). Unlike Stevens-Johnson
      syndrome or toxic epidermal necrolysis, AGEP is rarely life-threatening. Systemic
      involvement is not typical, and if present usually coincides with a mild
      elevation of the hepatic enzymes and a decrease in renal function. Hence, AGEP is
      known to have a good prognosis and to be life-threatening only in elderly
      patients or patients with chronic diseases. Herein, we report a case of AGEP in a
      young healthy male leading to systemic inflammatory response syndrome and to
      treatment in an intensive care unit after being treated with 5 different
      antibiotics. Initial symptoms were not indicative for AGEP and the patient's
      course of disease led promptly to critical cardiorespiratory symptoms and
      systemic inflammatory response syndrome. We assume that the administration of the
      5 different antibiotics resulted in type IV allergy as well as secondary
      infection with Enterococcus faecium and Staphylococcus aureus, while the
      underlying periodontitis also contributed to the severity of this case.

PMID- 29065397
TI  - Immune Therapy of Lympho-Hemopoietic Malignancies.

PMID- 29065398
TI  - A Call to Action to Develop Integrated Curricula in Cardiorenal Medicine.
AB  - With the adoption of the new definition and classification of cardiorenal
      syndrome (CRS) and its relevant subtypes, much attention has been placed on
      elucidating the mechanisms of heart and kidney interactions. Of great interest
      are the pathophysiological pathways by which acute heart failure may result in
      acute kidney injury (AKI; type 1), chronic heart failure accelerating the
      progression of chronic kidney disease (CKD; type 2), AKI provoking cardiac events
      (type 3), and CKD increasing the risk and severity of cardiovascular disease
      (type 4). A remarkable interest has also been placed on the acute and chronic
      systemic conditions, such as sepsis and diabetes, which simultaneously affect
      heart and kidney function (type 5). Furthermore, the physiology of acute and
      chronic heart-kidney cross talk is drawing attention to hemodynamics (fluids,
      pressures, flows, resistances, perfusion), physiochemical (electrolytes, pH, and
      toxins), and biological (inflammation, immune system activation, neurohormonal
      signals) processes. Common clinical scenarios call for recognition, knowledge,
      and skill in managing CRS. There is a clear need for medical and surgical
      specialists that are well versed in the pathophysiology and the clinical
      manifestations that arise in the setting of CRS. With this editorial, we are
      making a call to action to stimulate universities, medical schools, and teaching
      hospitals to create a core curriculum for cardiorenal medicine to better equip
      the physicians of the future for these common, serious, and frequently fatal
      syndromes.

PMID- 29065396
TI  - CD34+CD38-CD123+ Cells Are Present in Virtually All Acute Myeloid Leukaemia
      Blasts: A Promising Single Unique Phenotype for Minimal Residual Disease
      Detection.
AB  - BACKGROUND/AIMS: In CD34-positive acute myeloid leukaemia (AML), the leukaemia
      initiating event likely takes place in the CD34+CD38- cell compartment. CD123 has
      been shown to be a unique marker of leukaemic stem cells within the CD34+CD38-
      compartment. The aim of this study was to identify the percentage of CD34+CD38
      CD123+ cells in AML blasts, AML CD34+CD38- stem cells, and normal and
      regenerating bone marrow CD34+CD38- stem cells from non-myeloid malignancies.
      METHODS: Thirty-eight adult de novo AML patients with intention to treat were
      enrolled after the application of inclusion criteria from February 2012 to
      February 2017. The percentage of the CD34+CD38-CD123+ phenotype in the blast
      population at diagnosis was determined using a CD45-gating strategy and CD34+
      backgating by flow cytometry. We studied the CD34+CD38-CD123+ fraction in AML
      blasts at diagnosis, and its utility as a unique phenotype for minimal residual
      disease (MRD) of AML patients. RESULTS: CD123+ cells were present in 97% of AML
      blasts in patients at diagnosis (median 90%; range 21-99%). CD123+ cells were
      also present in 97% of the CD34+CD38- compartment (median 0.8164%, range 0.0262
      39.7%). Interestingly, CD123 was not present in normal and regenerating CD34+CD38
      bone marrow stem cells (range 0.002- 0.067 and 0.004-0.086, respectively).
      CONCLUSION: The CD34+CD38-CD123+ phenotype is present in virtually all AML blasts
      and it may be used as a unique single phenotype for MRD detection in AML
      patients.

PMID- 29065399
TI  - Definitive Radiotherapy for Primary Squamous Cell Carcinoma of the Vagina: Are
      High-Dose External Beam Radiotherapy and High-Dose-Rate Brachytherapy Boost the
      Best Treatment? Experience of Two Italian Institutes.
AB  - INTRODUCTION: We assessed the clinical outcome and survival of 70 patients with
      primary vaginal squamous cell carcinoma undergoing radiotherapy (RT) at the
      Divisions of Radiotherapy, University of Pisa and ASST Cremona between January
      1995 and June 2016. METHODS: 58 patients received external beam RT (EBRT) to the
      entire vagina, para-vaginal area and pelvic nodes (total dose: 45-50.4 Gy). 29
      patients (41.4%) received concomitant weekly cisplatin 40 mg/m2. 35 patients
      received an additional (15-36 Gy) high-dose-rate (HDR) brachytherapy (BT) boost
      and 13 received an additional (9-25 Gy) EBRT boost to the primary tumor site. 12
      women exclusively received HDR-BT up to a total dose of (30-58 Gy). RESULTS:
      Median overall survival (OS) was 85 months. A total RT dose of > 60 Gy was
      significantly associated with a better OS (p = 0.015). There was a trend for a
      better OS for patients aged < 70 years and for those undergoing EBRT to the
      entire vagina and pelvis plus BT boost. The most common grade 1-2 acute
      toxicities were diarrhea (24.1%) and cystitis (20.7%); grade 3 cystitis only
      occurred in 2 patients (3.4%). CONCLUSIONS: EBRT followed by BT boost seems to be
      the best treatment for vaginal carcinoma. The total dose of RT should be > 60 Gy.

PMID- 29065400
TI  - Dose-Dependent Effects of Binge-Like Methamphetamine Dosing on Dopamine and
      Neurotrophin Levels in Rat Brain.
AB  - This study investigated the acute effect of a dose range of low-to-moderate binge
      like methamphetamine treatments on the regional expression of neurotrophin
      proteins in the brain and serum 2 h after the last dose, in addition to assessing
      the behavioural effects and dopamine neurotransmitter changes produced. Male
      Sprague-Dawley rats received 4 subcutaneous doses of methamphetamine (0.5, 1, 2,
      and 4 mg/kg, or saline as a control) 2 h apart. Methamphetamine had a dose
      dependent stimulatory effect on locomotor activity over the 8 h of observation. A
      significant increase in dopamine concentration was observed in the frontal cortex
      with the highest dose of methamphetamine (2 h after the last dose). This effect
      was dose- and region-specific, as no significant increase was observed with lower
      doses, nor was a significant change observed in any other brain region tested. A
      similar dose- and region-specific increase in brain-derived neurotrophic factor
      (BDNF) was observed in the frontal cortex with the highest-dose regimen. No
      significant change occurred with lower doses of methamphetamine, or in any other
      brain region tested. A reduction in BDNF levels in the serum was also observed
      with the highest concentration, but not with lower doses. Collectively, this data
      highlights the importance of the frontal cortex in methamphetamine-induced
      effects, and also the similar dose-response effect of methamphetamine on dopamine
      and BDNF expression.

PMID- 29065401
TI  - Application of iTRAQ-Based Quantitative Proteomics Approach to Identify
      Deregulated Proteins Associated with Liver Toxicity Induced by Polygonum
      Multiflorum in Rats.
AB  - BACKGROUND/AIMS: Clinical reports on adverse reactions that result from Polygonum
      multiflorum (PM) and its preparations, especially regarding liver injury, have
      recently received widespread attention. This study aimed to investigate the
      mechanism of hepatotoxicity induced by different PM extracts through iTRAQ
      quantitative proteomics. METHODS: The different PM extracts were orally
      administrated for 90 days to rats, and the hepatotoxicity effect was evaluated
      through measurement of biochemical indexes, oxidative damage indexes and
      hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was
      investigated by iTRAQ quantitative proteomics. RESULTS: The results of
      biochemical and histopathological analyses showed that liver injury occurred in
      all groups of rats given by various PM extracts, which proved all of the PM
      extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ
      between the total extract group and the other groups through the results of
      biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity
      resulting from PM was mainly related to the abnormal activity of mitochondrion
      function-related oxidative phosphorylation pathways. CONCLUSION: This iTRAQ
      proteomics study revealed that the hepatotoxicity induced by PM is primarily
      related to the oxidative phosphorylation pathways. NADH dehydrogenase family
      proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting
      from PM.

PMID- 29065402
TI  - Vitamin E-Coated Dialyzer Inhibits Oxidative Stress.
AB  - AIM: To examine the effects of vitamin E-coated dialyzer on oxidative stress in
      vitro. METHODS: A dialyzer with a synthetic polymer membrane (APS-11SA) and
      vitamin E-coated dialyzer (VPS-11SA) were connected to a blood tubing line, and
      U937 cells were circulated in the device. The circulating fluid was collected at
      1, 2, 5, 10, 25, and 50 cycles, which are estimated numbers of passes through the
      dialyzer. Intracellular reactive oxygen species (ROS) production, malondialdehyde
      (MDA), and Cu/Zn-superoxide dismutase (SOD) were quantified. RESULTS:
      Intracellular ROS production was increased in the first cycle by APS-11SA and was
      decreased throughout the experiment by VPS-11SA. Intracellular ROS production in
      the VPS-11SA device was lower, and MDA levels were decreased. MDA levels were
      lower during VPS-11SA processing than during APS-11SA processing. Cu/Zn-SOD
      levels remained unchanged. CONCLUSION: Our results highlight anti-oxidative
      stress effects of a vitamin E-coated dialyzer.

PMID- 29065404
TI  - Urgent-Start Peritoneal Dialysis: The First Year of Brazilian Experience.
AB  - BACKGROUND: This study aimed to evaluate mechanical and infectious complications
      associated with urgent-start peritoneal dialysis (PD) and patients and technique
      survival in the first 180 days. METHODS: It was a prospective study that
      evaluated chronic patients who started unplanned PD using high-volume PD (HVPD)
      right after (<72 h) PD catheter placement. After hospital discharge, patients
      were treated with intermittent PD on alternate days in a dialysis unit until
      family training was provided. RESULTS: Fifty-one patients fulfilling the
      following criteria were included: age was 62.1 +/- 15 years, with diabetes as the
      main etiology of end-stage renal disease (39%), and uremia as the main dialysis
      indication (76%). Metabolic and fluid controls were achieved after 3 sessions of
      HVPD, and patients remained in intermittent PD for 23.2 +/- 7.2 days. Mechanical
      complications occurred in 25.7% and peritonitis rate was 0.5 episode/patient
      year. In the first 6 months, technique and patients survival rates were 86 and
      82.4% respectively. CONCLUSION: The PD modality was a feasible and safe
      alternative to hemodialysis in the urgent-start dialysis.

PMID- 29065403
TI  - Curcumin-Loaded Nanoparticles Protect Against Rhabdomyolysis-Induced Acute Kidney
      Injury.
AB  - BACKGROUND/AIMS: Rhabdomyolysis (RM) is a potentially life-threatening condition
      that results from the breakdown of muscle and consequent release of toxic
      compounds into circulation. The most common and severe complication of RM is
      acute kidney injury (AKI). This study aimed to evaluate the efficacy and
      mechanisms of action of curcumin-loaded nanoparticles (Cur-NP) for treatment of
      RM-induced AKI. METHODS: Curcumin-NP was synthesized using the nanocarrier
      distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to achieve a
      prolonged and constant drug release profile compared with the curcumin-free
      group. The anti-AKI effects of Curcumin-NP were examined both in vitro (myoglobin
      treated renal tubular epithelial HK-2 cells) and in vivo (glycerol-induced AKI
      model). RESULTS: Our results indicated that Curcumin-NP reversed oxidative
      stress, growth inhibition and cell apoptosis accompanied with down-regulation of
      apoptotic markers Caspase-3 and GRP-78 in vitro. In vivo studies revealed
      enhanced AKI treatment efficacy with Curcumin-NP as characterized by reduced
      serum creatine phosphokinase (CPK), creatinine (Cr) and urea and less severe
      histological damage in renal tubules. In addition, kidney tissues from Curcumin
      NP-treated AKI rats exhibited reduced oxidative stress, apoptosis, and cleaved
      Capase-3 and GRP-78 expression. CONCLUSION: Our results suggest that nanoparticle
      loaded curcumin enhances treatment efficacy for RM-induced AKI both in vitro and
      in vivo.

PMID- 29065405
TI  - Risk Factors for Uroseptic Shock in Patients with Urolithiasis-Related Acute
      Pyelonephritis.
AB  - OBJECTIVES: To analyze the risk factors of uroseptic shock induced by calculous
      acute pyelonephritis (APN). METHODS: This study included 69 patients (41 were
      women and 28 were men) who were admitted to our hospital for APN treatment
      associated with urolithiasis during the period from January 2005 to December
      2012. We reviewed the electronic medical records of these patients to analyze
      risk factors contributing to the development of uroseptic shock from APN in
      patients with urolithiasis. RESULTS: Urinary drainage with ureteral stent or
      nephrostomy was carried out in 62 cases. Septic shock requiring vasopressor
      infusion against circulatory collapse was observed in 25 patients, these patients
      showed significantly lower serum albumin levels and higher C-reactive protein
      (CRP) compared to patients who did not exhibit septic shock. Multivariate
      analysis revealed that serum albumin level and CRP were the significant risk
      factors for the development of uroseptic shock from calculous APN. CONCLUSIONS:
      Serum albumin level was the significant risk factor for the development of
      uroseptic shock from calculous APN. Emergency drainage to decompress the
      obstructed urinary tract is mandatory as an initial urological intervention for
      the patients with lower serum albumin level.

PMID- 29065407
TI  - Hypoxic Stress Upregulates the Expression of Slc38a1 in Brown Adipocytes via
      Hypoxia-Inducible Factor-1alpha.
AB  - The availability of amino acid in the brown adipose tissue (BAT) has been shown
      to be altered under various conditions; however, little is known about the
      possible expression and pivotal role of amino acid transporters in BAT under
      physiological and pathological conditions. The present study comprehensively
      investigated whether amino acid transporters are regulated by obesogenic
      conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the
      regulation of the expression of amino acid transporters by various stressors in
      brown adipocytes in vitro. The expression of solute carrier family 38 member 1
      (Slc38a1; gene encoding sodium-coupled neutral amino acid transporter 1) was
      preferentially upregulated in the BAT of both genetic and acquired obesity mice
      in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress
      through hypoxia-inducible factor-1alpha, which is a master transcription factor
      of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These
      results indicate that Slc38a1 is an obesity-associated gene in BAT and a hypoxia
      responsive gene in brown adipocytes.

PMID- 29065406
TI  - Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary
      Expansion of the Human Precuneus.
AB  - The precuneus is a major element of the superior parietal lobule, positioned on
      the medial side of the hemisphere and reaching the dorsal surface of the brain.
      It is a crucial functional region for visuospatial integration, visual imagery,
      and body coordination. Previously, we argued that the precuneus expanded in
      recent human evolution, based on a combination of paleontological, comparative,
      and intraspecific evidence from fossil and modern human endocasts as well as from
      human and chimpanzee brains. The longitudinal proportions of this region are a
      major source of anatomical variation among adult humans and, being much larger in
      Homo sapiens, is the main characteristic differentiating human midsagittal brain
      morphology from that of our closest living primate relative, the chimpanzee. In
      the current shape analysis, we examine precuneus variation in non-human primates
      through landmark-based models, to evaluate the general pattern of variability in
      non-human primates, and to test whether precuneus proportions are influenced by
      allometric effects of brain size. Results show that precuneus proportions do not
      covary with brain size, and that the main difference between monkeys and apes
      involves a vertical expansion of the frontal and occipital regions in apes. Such
      differences might reflect differences in brain proportions or differences in
      cranial architecture. In this sample, precuneus variation is apparently not
      influenced by phylogenetic or allometric factors, but does vary consistently
      within species, at least in chimpanzees and macaques. This result further
      supports the hypothesis that precuneus expansion in modern humans is not merely a
      consequence of increasing brain size or of allometric scaling, but rather
      represents a species-specific morphological change in our lineage.

PMID- 29065408
TI  - Low-Dose Allergen-Specific Immunotherapy Induces Tolerance in a Murine Model of
      Shrimp Allergy.
AB  - BACKGROUND: The efficacy and safety of allergen-specific immunotherapy (AIT) are
      highly dose-dependent. METHODS: We investigated the dosage effects of AIT and the
      underlying mechanisms in a murine model of shrimp hypersensitivity. BALB/c mice
      were sensitized with recombinant shrimp allergen rMet e 1 and challenged orally
      with a high dose of rMet e 1 to elicit an allergic response. These sensitized
      mice were then treated with a low (0.01 mg), medium (0.05 mg), or high dosage
      (0.1 mg) of rMet e 1 intraperitoneally before receiving a second oral challenge.
      The allergic responses and immunological changes in the gut were compared between
      animals receiving different dosages. RESULTS: We found that all sensitized mice
      that received rMet e 1 immunotherapy were desensitized, regardless of the dosage,
      and protected at the second oral challenge. Nevertheless, the mice in the high
      dosage group experienced severe systemic reactions during the treatment phase. In
      contrast, regulatory T (Treg) cell-associated genes were upregulated only in the
      low- and medium-dosage groups, and Foxp3+ cells were more abundant in the gut
      lymphoid tissues than in the high-dosage group. CONCLUSIONS: Our results
      demonstrate that low-dosage immunotherapy favors the induction of local Foxp3+
      Treg cells and the upregulation of regulatory cytokines. The safety advantages
      and long-term efficacy of low-dosage immunotherapy should be taken into
      consideration when developing immunotherapy dose schedules.

PMID- 29065409
TI  - Low-Frequency Components in Rat Pial Arteriolar Rhythmic Diameter Changes.
AB  - This study aimed to analyze the frequency components present in spontaneous
      rhythmic diameter changes in rat pial arterioles. Pial microcirculation was
      visualized by fluorescence microscopy. Rhythmic luminal variations were evaluated
      via computer-assisted methods. Spectral analysis was carried out on 30-min
      recordings under baseline conditions and after administration of acetylcholine
      (Ach), papaverine (Pap), Nomega-nitro-L-arginine (L-NNA) prior to Ach,
      indomethacin (INDO), INDO prior to Ach, charybdotoxin and apamin, and
      charybdotoxin and apamin prior to Ach. Under baseline conditions all arteriolar
      orders showed 3 frequency components in the ranges of 0.0095-0.02, 0.02-0.06, and
      0.06-0.2 Hz, another 2 in the ranges of 0.2-2.0 and 2.5-4.5 Hz, and another ultra
      low-frequency component in the range of 0.001-0.0095 Hz. Ach caused a significant
      increase in the spectral density of the frequency components in the range of
      0.001-0.2 Hz. Pap was able to slightly increase spectral density in the ranges of
      0.001-0.0095 and 0.0095-0.02 Hz. L-NNA mainly attenuated arteriolar responses to
      Ach. INDO prior to Ach did not affect the endothelial response to Ach.
      Charybdotoxin and apamin, suggested as endothelium-derived hyperpolarizing factor
      inhibitors, reduced spectral density in the range of 0.001-0.0095 Hz before and
      after Ach administration. In conclusion, regulation of the blood flow
      distribution is due to several mechanisms, one of which is affected by
      charibdotoxin and apamin, modulating the vascular tone.

PMID- 29065410
TI  - A Novel Positive Feedback Loop Between NTSR1 and Wnt/beta-Catenin Contributes to
      Tumor Growth of Glioblastoma.
AB  - BACKGROUND/AIMS: Neurotensin (NTS), an intestinal hormone, is profoundly
      implicated in cancer progression through binding its primary receptor NTSR1. The
      conserved Wnt/beta-Catenin pathway regulates cell proliferation and
      differentiation via activation of the beta-catenin/T-cell factor (TCF) complex
      and subsequent modulation of a set of target genes. In this study, we aimed to
      uncover the potential connection between NTS/NTSR1 signaling and Wnt/beta-Catenin
      pathway. METHODS: Genetic silencing, pharmacological inhibition and gain-of
      function studies as well as bioinformatic analysis were performed to uncover the
      link between NTS/ NTSR1 signaling and Wnt/beta-Catenin pathway. Two inhibitors
      were used in vivo to evaluate the efficiency of targeting NTS/NTSR1 signaling or
      Wnt/beta-Catenin pathway. RESULTS: We found that NTS/NTSR1 induced the activation
      of mitogen-activated protein kinase (MAPK) and the NF-kappaB pathway, which
      further promoted the expression of Wnt proteins, including Wnt1, Wnt3a and Wnt5a.
      Meanwhile, the mRNA and protein expression levels of NTSR1 were increased by the
      Wnt pathway activator Wnt3a and decreased by the Wnt inhibitor iCRT3 in
      glioblastoma cells. Furthermore, pharmacological inhibition of NTS/NTSR1 or
      Wnt/beta-Catenin signaling suppressed tumor growth in vitro and in vivo.
      CONCLUSION: These results reveal a positive feedback loop between NTS/NTSR1 and
      Wnt/beta-Catenin signaling in glioblastoma cells that might be important for
      tumor development and provide potential therapeutic targets for glioblastoma.

PMID- 29065411
TI  - Gut Microbiota and Host Metabolism: What Relationship.
AB  - A large number of genomic studies have reported associations between the gut
      microbiota composition and metabolic diseases such as obesity or type 2 diabetes.
      This led to the widespread idea that a causal relationship could exist between
      intestinal microbiota and metabolic diseases. At odds with this idea, some
      compelling studies reported that global changes in microbiota composition have no
      effect on the host metabolism in obese mice or humans. However, specific bacteria
      are able to confer host metabolic benefits, such as Akkermansia muciniphila or
      Prevotella copri, when they are given by gavage in obese mice. A crucial link by
      which gut bacteria communicate with the host mucosa is based on metabolites or
      low-molecular-weight compounds. Among them, short-chain fatty acids produced from
      the fermentation of dietary fibers initiate beneficial effects on the host
      metabolism via the activation of intestinal gluconeogenesis (a mucosal function
      exerting antidiabetic and antiobesity effects through the activation of gut-brain
      neural circuits). However, fermentation of short-chain fatty acids is a function
      that is widespread among the main bacterial phyla and thus weakly depends on
      microbiota composition. Therefore, even if some bacteria may confer on the host
      metabolic benefits, the causal role of microbiota in metabolic diseases is not
      established.

PMID- 29065413
TI  - An Evolutionary Genetic Perspective of Eating Disorders.
AB  - Eating disorders (ED) including anorexia nervosa (AN), bulimia nervosa (BN), and
      binge eating disorder (BED) affect up to 5% of the population in Western
      countries. Risk factors for developing an ED include personality traits, family
      environment, gender, age, ethnicity, and culture. Despite being moderately to
      highly heritable with estimates ranging from 28 to 83%, no genetic risk factors
      have been conclusively identified. Our objective was to explore evolutionary
      theories of EDs to provide a new perspective on research into novel biological
      mechanisms and genetic causes of EDs. We developed a framework that explains the
      possible interactions between genetic risk and cultural influences in the
      development of ED. The framework includes three genetic predisposition categories
      (people with mainly AN restrictive gene variants, people with mainly BED
      variants, and people with gene variants predisposing to both diseases) and a
      binary variable of either the presence or absence of pressure to be thin. We
      propose novel theories to explain the overlapping characteristics of the subtypes
      of AN (binge/purge and restrictive), BN, and BED. For instance,
      mutations/structural gene variants in the same gene causing opposite effects or
      mutations in nearby genes resulting in partial disequilibrium for the genes
      causing AN (restrictive) and BED may explain the overlap of phenotypes seen in AN
      (binge/purge).

PMID- 29065412
TI  - Circulating Cell-Free DNA Levels in Patients with Metastatic Renal Cell
      Carcinoma.
AB  - BACKGROUND: Limited data about biomarkers are available to predict the outcomes
      of targeted therapy in metastatic renal cell carcinoma (mRCC). Circulating cell
      free DNA (CFD) is elevated in various cancers. PATIENTS AND METHODS: We performed
      a prospective study of patients with mRCC who received targeted therapy in the
      Soroka Medical Center between 2013 and 2015. CFD levels were measured using a
      simple fluorometric assay. Blood samples for CFD were collected before treatment
      and at weeks 1, 4, 12, 18, and 24 of treatment. The normal cut-off level of CFD
      was defined as 800 ng/ml. The association of CFD with objective response,
      progression-free survival (PFS), and overall survival was tested, with adjustment
      for known confounding risk factors. RESULTS: A total of 23 patients were
      included; 18 were treated with first-line therapy and 5 with second- and third
      line therapies. Patients with normal pretreatment CFD level had a better PFS
      versus patients with increased levels (p = 0.023). In multivariate analysis,
      factors associated with PFS were pretreatment CFD levels (p = 0.020) and Heng
      risk (p = 0.006). CONCLUSIONS: Elevated pretreatment CFD levels measured using a
      simple fluorometric assay may be associated with a worse PFS in patients with
      mRCC. A larger prospective study is warranted in order to validate our
      observation.

PMID- 29065414
TI  - Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse
      Skeletal Muscle via AKT/mTOR/p70S6K Signaling.
AB  - BACKGROUND/AIMS: Skeletal muscle ischemia/reperfusion (I/R) injury is a common
      and severe disease. Sonic hedgehog (Shh) plays a critical role in post-natal
      skeletal muscle regeneration. In the present study, the role of Shh in skeletal
      muscle I/R injury and the mechanisms involved were investigated. METHODS: The
      expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were
      evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice
      were subjected to systemic administration of cyclopamine or one-shot treatment of
      a plasmid encoding the human Shh gene (phShh) to examine the effects of Shh on
      I/R injury. Moreover, mice were subjected to systemic administration of NVP
      BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered
      skeletal muscle protection. RESULTS: We found that the levels of Shh,
      AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio
      initially increased and then decreased at different time points post-I/R injury.
      Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle
      destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these
      protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited.
      CONCLUSION: Collectively, these data suggest that Shh signaling exerts a
      protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal
      muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting
      skeletal muscle from I/R injury.

PMID- 29065415
TI  - Evidence for an Association of ERCC1 Expression and Mismatch Repair Status with
      Overall Survival in Colorectal Cancer Patients.
AB  - BACKGROUND: The aim in this study was to determine if an association of excision
      repair cross-complementing group 1 (ERCC1) gene and mismatch repair (MMR) status
      with overall survival (OS) could be found from our analysis of a large cohort of
      Chinese colorectal cancer patients (CRC). METHODS: In total, 2,233 tissue samples
      isolated from individual CRC tumors were assessed by immunohistochemistry for the
      expression of ERCC1 and 4 MMR genes. RESULTS: The rates of proficient MMR (pMMR)
      and ERCC1 expression were 89.6 and 90.7%, respectively. We found that patients
      with positive ERCC1 expression and deficient (d)MMR status had higher overall
      survival (OS) than those with either positive ERCC1 and pMMR, negative ERCC1 and
      dMMR, or negative ERCC1 expression and pMMR status (OS 79 vs. 69 vs. 66 vs. 61%,
      hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.80-1.00; p = 0.043).
      Despite this finding, we found no statistical difference in OS between ERCC1
      positive and -negative CRC patients when ERCC1 expression was considered alone
      (OS 70 vs. 62%, HR 0.82, 95% CI 0.65-1.04; p = 0.11). CONCLUSION: Our results
      indicate that the combined examination of ERCC1 expression and dMMR status can be
      used to aid OS assessment in CRC patients.

PMID- 29065416
TI  - Bevacizumab in Combination with Platinum-Based Chemotherapy in Patients with
      Advanced Non-Squamous Non-Small Cell Lung Cancer with or without Brain
      Metastases: A French Cohort Study (EOLE).
AB  - OBJECTIVES: The aim of this study was to describe the characteristics of patients
      receiving bevacizumab plus first-line metastatic chemotherapy for non-squamous
      advanced non-small cell lung cancer (aNSCLC), with or without brain metastases,
      in routine clinical practice. Other objectives were to describe treatment
      efficacy, modalities of use, and safety. METHODS: For this non-interventional,
      prospective, national, multicentre study, data were collected every 3 months over
      18 months. RESULTS: Of the 407 patients analysed, 84 (21%) with brain metastases
      at bevacizumab initiation had poorer general health than patients with no brain
      metastases (Eastern Cooperative Oncology Group [ECOG] performance status score =
      2: 16 vs. 11%). All but 2 patients received bevacizumab (7.5 or 15 mg/kg/3 weeks
      in 99% of patients) in combination with doublet chemotherapy. Median progression
      free survival and overall survival did not differ significantly between patients
      with or without brain metastases (6.5 months, 95% CI 5.7-8.1 vs. 6.9 months, 95%
      CI 5.9-7.6, p = 0.57; 14.5 months, 95% CI 10.0 vs. 12.5 months, 95% CI 10.1-14.7,
      p = 0.33). In 30 and 32% of the patients, respectively, at least one serious
      adverse event was reported, with a causal relationship to bevacizumab in 20 and
      21% of the patients. CONCLUSION: This study confirmed in a real-life setting the
      safety profile and survival benefits of first-line chemotherapy with bevacizumab
      in aNSCLC patients with brain metastases.

PMID- 29065417
TI  - Comparisons between Psychiatric Symptoms of Patients with Anti-NMDAR Encephalitis
      and New-Onset Psychiatric Patients.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a
      potentially lethal autoimmune disease. Early diagnosis and immunotherapy can
      improve prognosis; however, early prominent psychiatric symptoms have led to
      misdiagnosis in numerous cases, delaying diagnosis and treatment. This study
      aimed to explore the clinical features and psychiatric symptoms of anti-NMDAR
      encephalitis and the association between antibody titers and psychiatric
      symptoms. METHODS: In this retrospective study, 43 patients with anti-NMDAR
      encephalitis and 70 new-onset psychiatric patients were enrolled. Psychiatric
      symptoms were assessed by trained psychiatrists using the Positive and Negative
      Syndrome Scale. RESULTS: There were significant differences in psychiatric
      symptoms between the antibody-positive and antibody-negative groups. The item
      scores for poor rapport (p < 0.01), difficulty in abstract thinking (p < 0.01),
      lack of spontaneity and flow of conversation (p < 0.01), unusual thought content
      (p < 0.01), and disorientation (p < 0.01) were significantly higher in the
      antibody-positive group, while the item scores for delusions (p < 0.01) were
      significantly higher in the antibody-negative group. These differences all
      remained significant after Holm-Bonferroni correction. In the antibody-positive
      group, scores for each item, subscale, and factor increased with increases in
      antibody titer, particularly for delusions (p < 0.05) and hallucinatory behavior
      (p < 0.01). Thereafter, only hallucinatory behavior remained significant.
      CONCLUSIONS: Patients with anti-NMDAR encephalitis with initial psychiatric
      symptoms may have the following characteristics: poor rapport, difficulty in
      abstract thinking, lack of spontaneity and flow of conversation, unusual thought
      content, and disorientation. Furthermore, antibody titer may be associated with
      psychiatric symptom severity, especially in hallucinatory behavior.

PMID- 29065418
TI  - Characterization of a Major Allergen from Mongolian Oak, Quercus mongolica, a
      Dominant Species of Oak in Korea.
AB  - BACKGROUND: Oaks are the most common trees in Korean forests, and Mongolian oak,
      Quercus mongolica, is the dominant species. However, no allergen has been
      characterized from Mongolian oak. In this study, we tried to characterize a major
      allergen from Mongolian oak. METHODS: A molecule homologous to pathogenesis
      related 10 (PR-10)-like protein, Que m 1, was cloned by RT-PCR. Its recombinant
      protein, along with Que a 1, an allergen from white oak (Q. alba), was produced.
      The allergenicity and diagnostic value of recombinant Que m 1, Que a 1, and Bet v
      1 proteins were compared by ELISA using sera from oak-sensitized subjects. A
      basophil activation test was also performed using CD63 expression as an
      activation marker. RESULTS: Que m 1 sequence shares 57.5-96.2% amino acid
      sequence identity with PR-10-like allergens from various plants. Specific IgE to
      recombinant Que m 1, Que a 1, and Bet v 1 were detected in 92.0, 74.0, and 38.0%
      of 50 serum samples from Korean tree pollinosis patients. Recombinant Que m 1 was
      able to inhibit IgE reactivity to Que a 1 and Bet v 1, indicating its strong
      cross-reactivity. The activation patterns of basophils from 5 patients were
      similar in terms of the CD63 expression and protein concentration of challenged
      Bet v 1 and Que m 1. CONCLUSIONS: A major allergen, Que m 1, was cloned, and its
      recombinant protein was produced from Mongolian oak, a dominant species in Korea.
      Recombinant Que m 1 is potentially useful for the diagnosis and treatment of tree
      pollinosis in Korea.

PMID- 29065420
TI  - Cellular Immunotherapy in B-Cell Malignancy.
AB  - In recent years, cellular immunotherapy in B-cell malignancies has been driven by
      adoptive transfer of genetically engineered T cells expressing chimeric antigen
      receptors (CARs). CARs consist of a single chain variable fragment (scFv) of a
      monoclonal antibody, a spacer domain, a transmembrane domain, an intracellular
      signaling domain, and additional costimulatory domains. The bulk of clinical data
      available is on CD19-targeting CAR T cells for the treatment of B-cell acute
      lymphocytic leukemia (B-ALL), chronic lymphocytic leukemia, and B-cell non
      Hodgkin lymphoma. Results so far have been promising with impressive rates and
      depth of remission especially among B-ALL patients. However, CAR T-cell therapy
      is a complex multi-step process, and clinical trials so far differ profoundly in
      CAR construct used, gene transfer method, composition of the cellular product,
      lymphodepletion, and CAR T-cell dose used. Randomized trials will be needed to
      conclusively evaluate the implications of these differences. The treatment
      concept is associated with significant neurotoxicity and potentially lethal
      cytokine release syndrome, both of which require specific management.
      Improvements in CAR design may help to overcome toxicity, the effects of an
      immunosuppressive microenvironment, and tumor escape by development of antigen
      negative clones. This review will explain the mechanism of action, summarize the
      clinical experience with this treatment modality so far, and explore future
      developments in the field.

PMID- 29065421
TI  - Checkpoint Inhibition in Non-Hodgkin's Lymphoma.
AB  - As patients continue to die from malignant lymphoma, novel treatment options
      continue to be warranted. To successfully grow and spread, tumor cells need to
      escape the immune system; therefore, the augmentation or restoration of immune
      effectors against the malignant cell could be of great value, as shown, e.g., for
      allogeneic transplantation. A deepened understanding of the regulation of
      activation and inhibition of the T cell-based effector mechanisms has led to the
      development of drugs that are able to modify specific checkpoints of this system
      and thereby raise an immune response against tumor cells. With dramatic responses
      observed in Hodgkin's disease (HD), interest has risen to explore these drugs in
      non-Hodgkin's lymphoma (NHL). Available data underline the potential of
      checkpoint inhibitors in a variety of lymphoma entities, such as primary
      mediastinal B cell lymphoma (PMBCL) or central nervous system (CNS) lymphoma, and
      there is hope that a significant proportion of patients will finally benefit.
      However, intensive efforts are needed to develop optimal screening tools,
      combinations, and sequences to explore the full potential of these new classes of
      therapeutic agents.

PMID- 29065419
TI  - Cognitive Aging in Dogs.
AB  - A decline in the physical or mental health of older dogs can be a challenge for
      the owners, whose relationship with their dog is compromised by the cognitive and
      behavioral changes in their dogs. Although dog owners tend to consider many
      physiological and behavioral changes in old dogs as part of the normal aging
      process, it is important to differentiate between normal aging and pathologic
      aging, since behavioral changes may be the first indication of declining health
      and welfare in old dogs. Most reviews on cognitive aging in dogs have focused on
      translational approaches to human Alzheimer's disease; from a practical
      perspective, however, understanding normal cognitive aging in pet dogs and
      screening cognitively affected dogs are important in their own right. Here we
      review the literature on different cognitive functions that decline during aging,
      signs of cognitive dysfunction, screening methods, and preventive measures for
      age-related cognitive decline. Moreover, we discuss the drawbacks of using
      questionnaires as subjective measures of aging and propose the development of
      objective methods to distinguish normal cognitive aging from severe cognitive
      dysfunction. We suggest that multi-targeted approaches that combine owner
      evaluated questionnaires with neuropsychological tests can be most effective in
      screening cognitively affected dogs from normally aging dogs. Regarding
      preventive measures, we conclude that combinations of dietary intervention and
      behavioral enrichment may be more beneficial than single-pathway manipulations in
      delaying cognitive aging or retaining various cognitive functions during aging.

PMID- 29065423
TI  - Efficacy, Safety and Mucosal Healing of Methotrexate in a Large Longitudinal
      Cohort of Inflammatory Bowel Disease Patients.
AB  - BACKGROUND/AIMS: Evidence for the effectiveness of methotrexate (MTX) in treating
      inflammatory bowel disease (IBD) is still incomplete. This study assessed the
      effectiveness, safety and mucosal healing in IBD patients treated with MTX in the
      Swiss IBD Cohort. METHODS: Efficacy was defined by physician assessment or by CD
      activity index <150 points for Crohn's disease (CD) or Modified Truelove and
      Witts activity index <4 points for ulcerative colitis (UC), measured at least
      after 3 months of MTX therapy. Mucosal healing was evaluated after 3 months or
      more of therapy. RESULTS: MTX was administered to 341 patients (262 CD; 79 UC)
      out of 2,660 patients. MTX effectiveness was 59.5% (128/215) in CD and 40.0%
      (24/60) in UC (chi2 = 7.2409, p = 0.007). Among patients on MTX therapy at the
      time of analysis, remission was obtained in 87.4% (76/87) and 69.2% (9/13) for CD
      and UC patients respectively. The median duration of MTX therapy was 40 months
      for CD and 15 months for UC. Occurrence of adverse events was the first reason
      for treatment discontinuation (39.4% of all cases). The rate of mucosal healing
      with MTX was 9.5% for CD and 25% for UC patients respectively. CONCLUSION: MTX
      therapy was effective for the induction and maintenance therapy in IBD patients,
      with only a modest mucosal healing ability.

PMID- 29065424
TI  - Checkpoint Inhibition in Hodgkin Lymphoma - a Review.
AB  - Physiological immune checkpoint pathways are important to regulate self
      tolerance, limit immune reactions, and moderate autoimmunity. Various cancers are
      commonly exploiting these mechanisms to evade the host immune system by
      restraining a durable, efficient anti-tumor immune response. Immune checkpoints
      include, but are not limited to, the programmed death 1 (PD1) and the cytotoxic T
      lymphocyte-associated protein-4 (CTLA4) axis, which are both druggable by
      monoclonal antibodies referred to as checkpoint inhibitors (CIs). To date, the
      anti-PD1 antibodies nivolumab and pembrolizumab are approved for relapsed or
      refractory classical Hodgkin lymphoma (cHL) due to high response rates with a
      favorable yet distinct safety profile, and other agents are under investigation.
      This review summarizes the available preclinical and clinical data including the
      toxicity and efficacy of different CIs in cHL. It also provides future
      perspectives based on ongoing clinical trials, potentially synergistic
      combinatory approaches, and their fit in the therapeutic landscape in cHL.

PMID- 29065422
TI  - Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory
      Cortex of Rats.
AB  - BACKGROUND/AIMS: The onset response to a single tone as measured by
      electroencephalography (EEG) is diminished in power and synchrony in
      schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80
      Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr)
      system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced
      similar deficits to tone stimuli in rats. METHODS: Experiment 1 tested the effect
      of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on
      intracranial EEG recorded over the auditory cortex in rats. Experiment 2
      evaluated the effect of PCP after acute administration of saline or PCP (5
      mg/kg), after continuous subchronic administration of saline or PCP (5
      mg/kg/day), and after a week of drug cessation. In both experiments, a time
      frequency analysis quantified mean power (MP) and phase locking factor (PLF)
      between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones,
      and EEG spectral power in the absence of auditory stimuli. RESULTS: Acute PCP
      increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between
      approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band
      increase in EEG power that extended into gamma range frequencies. There were no
      consistent effects of subchronic administration on gamma range activity. Acute
      PCP increased ERP amplitudes for the P16 and N70 components. CONCLUSIONS:
      Findings suggest that acute PCP-induced NMDAr hypofunction has differential
      effects on neural power and synchrony which vary with dose, time course of
      administration and EEG frequency. EEG synchrony and power appear to be sensitive
      translational biomarkers for disrupted NMDAr function, which may contribute to
      the pathophysiology of schizophrenia and other neuropsychiatric disorders.

PMID- 29065425
TI  - Multimodal Evaluation of the Fellow Eye of Patients with Retinal Angiomatous
      Proliferation.
AB  - INTRODUCTION: We conducted a multimodal, cross-sectional evaluation. METHODS:
      Eyes were divided into 4 study groups: controls, early/intermediate age-related
      macular degeneration (AMD), fellow eyes of retinal angiomatous proliferation
      (RAP), and RAP eyes. Patients were evaluated with spectral-domain optical
      coherence tomography (OCT), enhanced depth imaging-OCT, and OCT angiography
      (OCTA). OCTA images were processed to generate maps of the vessel density and
      perfusion density of the superficial and deep retinal layers (SRL and DRL) and
      the choriocapillaris level (CL). The thickness of the outer nuclear layer and
      choroid was manually assessed. RESULTS: We included 135 eyes of 100 patients (51
      controls, 30 AMD, 42 RAP, and 12 fellow eyes). The fellow eyes showed a
      significantly lower vascular perfusion of the SRL, DRL, and CL (p < 0.02) than
      the early/intermediate AMD and control eyes did. Similarly, RAP eyes presented a
      lower vascular perfusion of the DRL and CL (p < 0.05). Besides, structural
      analyses of the fellow eyes and RAP eyes revealed a significantly higher
      prevalence of macular pigmentary changes, atrophy of the retinal pigment
      epithelium, hyperreflective "clumps" above flat drusen, amongst others, than
      early/intermediate AMD and control eyes (p < 0.05). CONCLUSION: We present the
      first report on the OCTA analysis of the fellow eye of patients with RAP. The
      reduced perfusion density and vessel density observed contributes, in association
      with clearly defined structural changes, to a wider characterization of RAP as a
      distinctive phenotype.

PMID- 29065428
TI  - Molecular Analysis Confirms that FKRP-Related Disorders are Underdiagnosed in
      Mexican Patients with Neuromuscular Diseases.

PMID- 29065426
TI  - Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine
      related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk
      colon cancer patients.
AB  - BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) catabolises ~85% of the
      administered dose of fluoropyrimidines. Functional DPYD gene variants cause
      reduced/abrogated DPD activity. DPYD variants analysis may help for defining
      individual patients' risk of fluoropyrimidine-related severe toxicity. METHODS:
      The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6
      months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary
      pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G,
      rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A
      rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were
      retrospectively tested for associations with ?grade 3 fluoropyrimidine-related
      adverse events (FAEs). An association analysis and a time-to-toxicity (TTT)
      analysis were planned. To adjust for multiple testing, the Benjamini and
      Hochberg's False Discovery Rate (FDR) procedure was used. RESULTS: FAEs occurred
      in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs
      occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At
      multivariate TTT analysis, significant associations were found for *6 rs1801160 A
      allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and
      rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs
      (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant
      alleles were significantly associated with time to neutropenia. CONCLUSIONS: This
      study adds evidence on the role of DPYD pharmacogenetics for safety of patients
      undergoing fluoropyrimidine-based chemotherapy.

PMID- 29065429
TI  - Racial/Ethnic Differences in Labor Induction in a Contemporary US Cohort: A
      Retrospective Cohort Study.
AB  - OBJECTIVE: To examine labor induction by race/ethnicity and factors associated
      with disparity in induction. STUDY DESIGN: This is a retrospective cohort study
      of 143,634 women eligible for induction >=24 weeks' gestation from 12 clinical
      centers (2002-2008). Rates of labor induction for each racial/ethnic group were
      calculated and stratified by gestational age intervals: early preterm (240/7
      336/7), late preterm (340/7-366/7), and term (370/7-416/7 weeks). Multivariable
      logistic regression examined the association between maternal race/ethnicity and
      induction controlling for maternal characteristics and pregnancy complications.
      The primary outcome was rate of induction by race/ethnicity. Inductions that were
      indicated, non-medically indicated, or without recorded indication were also
      compared. RESULTS: Non-Hispanic black (NHB) women had the highest percentage rate
      of induction, 44.6% (p < 0.001). After adjustment, all racial/ethnic groups had
      lower odds of induction compared with non-Hispanic white (NHW) women. At term,
      NHW women had the highest percentage rate (45.4%) of non-medically indicated or
      induction with no indication (p < 0.001). CONCLUSION: Compared with other
      racial/ethnic groups, NHW women were more likely to undergo non-medically
      indicated induction at term. As labor induction may avoid the occurrence of
      stillbirth, whether this finding explains part of the increased risk of
      stillbirth for NHB women at term merits further research.

PMID- 29065427
TI  - Tenascin C in colorectal cancer stroma is a predictive marker for liver
      metastasis and is a potent target of miR-198 as identified by microRNA analysis.
AB  - BACKGROUND: Tumour stroma has important roles in the development of colorectal
      cancer (CRC) metastasis. We aimed to clarify the roles of microRNAs (miRNAs) and
      their target genes in CRC stroma in the development of liver metastasis. METHODS:
      Tumour stroma was isolated from formalin-fixed, paraffin-embedded tissues of
      primary CRCs with or without liver metastasis by laser capture microdissection,
      and miRNA expression was analysed using TaqMan miRNA arrays. RESULTS:
      Hierarchical clustering classified 16 CRCs into two groups according to the
      existence of synchronous liver metastasis. Combinatory target prediction
      identified tenascin C as a predicted target of miR-198, one of the top 10 miRNAs
      downregulated in tumour stroma of CRCs with synchronous liver metastasis.
      Immunohistochemical analysis of tenascin C in 139 primary CRCs revealed that a
      high staining intensity was correlated with synchronous liver metastasis
      (P<0.001). Univariate and multivariate analyses revealed that the tenascin C
      staining intensity was an independent prognostic factor to predict postoperative
      overall survival (P=0.005; n=139) and liver metastasis-free survival (P=0.001;
      n=128). CONCLUSIONS: Alterations of miRNAs in CRC stroma appear to form a
      metastasis-permissive environment that can elevate tenascin C to promote liver
      metastasis. Tenascin C in primary CRC stroma has the potential to be a novel
      biomarker to predict postoperative prognosis.

PMID- 29065430
TI  - Lipidomic Changes in Skeletal Muscle in Patients after Biliopancreatic Diversion.
AB  - The mechanisms behind the fast improvements of insulin sensitivity and release of
      the diabetic metabolic state after bariatric surgery are still not completely
      understood. To further elucidate the effects on the individual cellular level, we
      applied mass spectrometry to investigate the changes in the lipidomic profile of
      skeletal muscle cells before and after biliopancreatic diversion in six patients.
      We found a decrease in lipid storage species, mainly triacylglycerides (e. g.,
      TAG 52:2 from 19.84 to 13.26 mol%; p=0.028), and an increase in structural and
      signaling lipids, including phosphatidylcholines [PC 36:2 (18:1/18:1) from 0.12
      to 0.65 mol%; p=0.046], phosphatidylinositols (PI 36:2 from 0.008 to 0.039 mol%;
      p=0.046), and cardiolipins (CL 72:8 from 0.16 to 1.22 mol%; p=0.043). The
      proportional increase in structural lipids was directly and the decrease in TAGs
      was inversely correlated to improved post-operative insulin sensitivity, measured
      by euglycemic hyperinsulinemic clamp. Thus, short-term recovery of insulin
      sensitivity after biliopancreatic diversion may, beside gut hormonal adaptation,
      mechanical factors, shifts in the gut microbiome, and changes in bile acid and
      phospholipid metabolism, additionally be attributed to a metabolic recovery of
      skeletal muscle cells, reflected by normalization of the cellular lipidomic
      profile. Further studies are needed to investigate whether improved insulin
      sensitivity of skeletal muscle might be directly associated with the degradation
      of ectopic triglycerides, thereby reducing the reservoir of lipotoxic
      intermediates, which might interfere with insulin signaling and hamper
      mitochondrial metabolism.

PMID- 29065433
TI  - Primary Aldosteronism: The Next Five Years.
AB  - The management of primary aldosteronism is widely varied within various published
      guidelines, with very little in the way of data supporting the choice of one
      variation over others. Current estimates of prevalence are probably accurate for
      aldosterone producing adenoma, but fall very short of that for bilateral adrenal
      hyperplasia. Discovery at the level of basic science has proven illuminating over
      the past 6 years in terms of unilateral disease and both somatic and germline
      mutations, with much less focus on the much more common bilateral disease;
      Attempts at harmonization have begun - for example, criteria for
      complete/partial/absent cure after adrenalectomy for unilateral disease; again
      focus on bilateral disease is muted. A number of possibilities are suggested as
      agenda for active consideration and change, across a wide range of areas -
      referral patterns, screening, confirmation and lateralization, what will be
      needed is discussion and agreement, to fill the lacunae within the current
      guidelines. Those involved will want to change to make such an agenda possible.

PMID- 29065431
TI  - Liver Fat Content in People with Pituitary Diseases: Influence of Serum IGF1
      Levels.
AB  - Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity,
      metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with
      endocrinopathies. However, the relationship between endocrine diseases and the
      development of NAFLD is not well known. In this study, we set out to determine
      whether liver fat content (LFC) was associated with IGF1 levels in people with
      pituitary diseases (PD). Eighty-nine patients with pituitary diseases and 74
      healthy controls were included in this study. LFC was measured using MRI. Hepatic
      steatosis was defined as LFC>5.5%. Patients with PD were older, and had a higher
      BMI than healthy controls. LFC was significantly higher in people with PD than in
      controls (6.5% vs. 3.2%; p<0.001). LFC was negatively associated with the IGF1
      level. The prevalence of steatosis was higher in PD patients than in controls
      (36.3% vs. 14.8%; p=0.002). In multivariate analysis, which included patients and
      controls, the predictive variables for steatosis were age, BMI and IGF1 levels,
      whereas the presence of pituitary diseases and gender were not associated with
      steatosis. Our data showed that LFC was strongly associated with IGF1 levels.
      These results suggest that steatosis associated with PD is probably a consequence
      of a low IGF1 level in these patients.

PMID- 29065432
TI  - PreImplantation Factor (PIF*) Regulates Stress-Induced Adrenal Steroidogenesis
      and Anti-Inflammatory Cytokines: Potential Application for Bioartificial Adrenal
      Transplant.
AB  - The main treatment algorithm for adrenal insufficiency is hormonal replacement,
      however, inadequate hormone substitution often leads to severe side effects.
      Adrenal cell transplantation could be a more effective alternative but would
      require life-long immune suppressive therapy. PreImplantation Factor (PIF) is an
      endogenous peptide secreted by viable human embryos that leads to maternal
      tolerance without immunosuppression. PIF could be effective for xenogeneic cell
      transplantation such as of bovine adrenocortical cells (BAC), which are used for
      bioartificial adrenal gland development that may more effectively restore complex
      adrenal functions. We report here that PIF exerts a dual regulatory effect on BAC
      by targeting mostly hyper-activated cells to specifically reduce
      adrenocorticotropic hormone (ACTH)-stimulated cortisol secretion. Reverse
      transcription real time PCR analysis revealed that PIF modulates the expression
      of two genes in the cortisol synthesis pathway, Steroidogenic Factor 1 (SF1), an
      activator of steroidogenesis, and the downstream steroidogenic enzyme Cytochrome
      P450 17A1 (CYP17A1). PIF increased basal expression of SF1 and CYP17A1 regardless
      of the activation level of the adrenocortical cells. In contrast, following ACTH
      stimulation, PIF reduced SF1 expression and induced expression of the immune
      suppressing anti-inflammatory cytokine IL10 only in the hyper-activated cells,
      suggesting both a protective and immune tolerant function. In conclusion, PIF
      regulates stress-induced adrenal steroidogenesis and immune tolerance in BAC,
      supporting a potential clinical application to reduce rejection by the host's
      immune response following xenotransplantation.

PMID- 29065434
TI  - Unanswered Questions in the Genetic Basis of Primary Aldosteronism.
AB  - Over the past six years, the genetic basis of a significant fraction of primary
      aldosteronism (PA) cases has been solved. Breakthrough discoveries include the
      role of somatic variants in the KCNJ5, CACNA1D, ATP1A1, and ATP2B3 genes as
      causes of aldosterone-producing adenomas (APAs), and the recognition of three
      novel hyperaldosteronism syndromes with germline variants in the KCNJ5, CACNA1D,
      and CACNA1H genes. The description of somatic variants in CACNA1D and ATP1A1 in
      aldosterone-producing cell clusters (APCCs) suggests that these clusters are
      precursors of some aldosterone-producing adenomas. Yet, a number of questions
      remain unanswered. These include the genetic basis of about 40% of APAs without
      somatic variants in known genes. Do technical issues explain this finding, or are
      the unexplained APAs due to somatic copy number variation or rare variants in
      thus-far undiscovered genes? Similarly, the role of CTNNB1 (beta catenin)
      variants in APA pathogenesis is still unclear. The major question to be solved is
      the genetic basis of bilateral adrenal hyperplasia (BAH). Is BAH due to the
      bilateral occurrence of APCCs, to germline variants, or perhaps due to unknown
      serum factors? Lastly, the etiology of unsolved cases of apparently familial
      hyperaldosteronism remains to be discovered. It is expected that genetic studies
      over the next few years will lead to answers to at least some of the questions
      raised.

PMID- 29065435
TI  - Graph Theoretical Analysis, In Silico Modeling, Synthesis, Anti-Microbial and
      Anti-TB Evaluation of Novel Quinoxaline Derivatives.
AB  - BACKGROUND: We designed to synthesize a number of 2-(2-(substituted benzylidene)
      hydrazinyl)-N-(4-((3-(phenyl imino)-3,4-dihydro quinoxalin-2(1 H)-ylidene)amino)
      phenyl) acetamide S1-S13: with the hope to obtain more active and less toxic anti
      microbial and anti-TB agents. METHODS: A series of novel quinoxaline Schiff bases
      S1-S13: were synthesized from o-phenylenediamine and oxalic acid by a multistep
      synthesis. In present work, we are introducing graph theoretical analysis to
      identify drug target. In the connection of graph theoretical analysis, we
      utilised KEGG database and Cytoscape software. All the title compounds were
      evaluated for their in-vitro anti-microbial activity by using agar well diffusion
      method at three different concentration levels (50, 100 and 150 ug/ml). The MIC
      of the compounds was also determined by agar streak dilution method. RESULTS: The
      identified study report through graph theoretical analysis were highlights that
      the key virulence factor for pathogenic mycobacteria is a eukaryotic-like
      serine/threonine protein kinase, termed PknG. All compounds were found to display
      significant activity against entire tested bacteria and fungi. In addition the
      synthesized scaffolds were screened for their in vitro antituberculosis (anti-TB)
      activity against Mycobacterium tuberculosis (Mtb) strain H37Ra using standard
      drug Rifampicin. CONCLUSION: A number of analogs found markedly potent anti
      microbial and anti-TB activity. The relationship between the functional group
      variation and the biological activity of the evaluated compounds were well
      discussed. The observed study report was showing that the compound S6: (4-nitro
      substitution) exhibited most potent effective anti-microbial and anti-TB activity
      out of various tested compounds.

PMID- 29065436
TI  - Hot avulsion may be effective as salvage treatment for focal Barrett's esophagus
      remaining after endoscopic therapy for dysplasia or early cancer: a preliminary
      study.
AB  - BACKGROUND AND STUDY AIM: Both endoscopic mucosal resection (EMR) and
      radiofrequency ablation (RFA) are used to treat Barrett's esophagus (BE)
      complicated by dysplasia and intramucosal cancer. However, focal areas of BE can
      remain after otherwise successful application of these techniques. We report the
      results of hot avulsion using a hot biopsy forceps to resect these residual focal
      areas. PATIENTS AND METHODS: This was a retrospective study from a prospective
      database in a tertiary reference center from August 2013 to May 2015. All
      included patients had undergone hot avulsion for eradication of residual focal
      areas of BE that were <= 1 cm and not suspicious for dysplasia, following at
      least one previous endoscopic treatment for dysplasia or intramucosal cancer.
      RESULTS: 35 patients harboring 124 residual areas of 1 - 7 mm were treated with
      hot avulsion. After a mean follow-up of 17.4 months, all patients achieved
      complete eradication of residual focal BE. One of the patients required a second
      hot avulsion treatment. Hot avulsion provided samples in all cases but limited
      the assessment of dysplasia (cautery artifact) in 20.2 % of them. The only
      complication was bleeding in two patients, which was easily stopped by soft
      coagulation. CONCLUSIONS: Hot avulsion appears to be effective and safe in
      removing focal BE <= 1 cm at its greatest length remaining after endoscopic
      treatment for dysplasia or early cancer. Further studies are required before this
      technique can be considered the standard of care.

PMID- 29065437
TI  - BASIC (BLI Adenoma Serrated International Classification) classification for
      colorectal polyp characterization with blue light imaging.
AB  - BACKGROUND AND STUDY AIM: Advanced endoscopic imaging has revolutionized the
      characterization of lesions during colonoscopy. The aim of this study was to
      create a new classification for differentiating subcentimetric hyperplastic and
      adenomatous polyps, and deeply invasive malignant lesions using blue-light
      imaging (BLI) with high definition, with and without optical magnification, as
      well as to assess its interobserver concordance. METHODS: A video library
      consisting of 48 videos/still images (with/without optical magnification) from 24
      histologically verified polyps/cancer with BLI was prospectively created. In the
      first step, seven endoscopists with experience in electronic chromoendoscopy
      reviewed 12 BLI videos/still images with/without magnification representative of
      the different histotypes, and individually identified possible descriptors. In
      the second step, these descriptors were categorized and summarized with a
      modified Delphi methodology. In the third step, the seven endoscopists
      independently reviewed the remaining 36 videos/still images with/without optical
      magnification, and the interobserver agreement for the new descriptors was
      assessed. The interobserver agreement between endoscopists was assessed using
      Gwet's AC1. RESULTS: By reviewing the initial 12 videos/still images, 43
      descriptors were proposed. By a modified Delphi process, the endoscopists
      eventually agreed on summarizing 12 descriptors into three main domains. The main
      domains identified were: polyp surface (mucus, yes/no; regular/irregular;
      [pseudo]depressed, yes/no), pit appearance (featureless, yes/no; round/nonround
      with/without dark spots; homogeneous/heterogeneous distribution with/without
      focal loss), and vessels (present/absent, lacy, pericryptal, irregular).
      Interobserver agreement for the polyp surface domain appeared to be almost
      perfect for mucus (AC1 0.92 with and 0.88 without optical magnification),
      substantial for the regular/irregular surface (AC1 0.67 with and 0.66 without
      optical magnification). For the pit appearance domain, interobserver agreement
      was good for featureless (AC1 0.9 with and 0.8 without optical magnification),
      and round/nonround (AC1 0.77 with and 0.69 without optical magnification)
      descriptors, but less consistent for the homogeneity of distribution (AC1
      with/without optical magnification 0.58). Agreement was almost perfect for the
      vessel domain (AC1 0.81 - 0.85). CONCLUSIONS: The new BASIC classification takes
      into account both morphological features of the polyp, as well as crypt and
      vessel characteristics. A high concordance among the observers was shown for most
      of the summarized descriptors. Optical magnification had a beneficial effect in
      terms of interobserver agreement for most of the descriptors.

PMID- 29065439
TI  - Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta
      analysis of randomized trials.
AB  - : BACKGROUND AND STUDY AIMS : Recommendations on adjuvant use with bowel
      preparations remain disparate. We performed a meta-analysis determining the
      clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium
      phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens.
      METHODS: Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and
      ISI Web of knowledge for randomized trials from January 1980 to April 2016 that
      assessed preparations with or without adjuvants, given in split and non-split
      dosing, and PEG high- (> 3 L) or low-dose (<= 2 L) regimens. Bowel cleansing
      efficacy was the primary outcome. Secondary outcomes included patient willingness
      to repeat the procedure, and polyp and adenoma detection rates. RESULTS: Of 3093
      citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an
      adjuvant compared with no adjuvant, irrespective of the type of preparation and
      mode of administration, yielded improvements in bowel cleanliness (odds ratio
      [OR] 1.23 [1.01 - 1.51]) without greater willingness to repeat (OR 1.40 [0.91 -
      2.15]). Adjuvants combined with high-dose PEG significantly improved colon
      cleansing (OR 1.96 [1.32 - 2.94]). The odds for achieving adequate preparation
      with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR
      0.95 [0.73 - 1.22]), but yielded improved tolerance (OR 3.22 [1.85 - 5.55]).
      However, split high-dose PEG yielded superior cleanliness to low-dose PEG with
      adjuvants (OR 2.53 [1.25 - 5.13]). No differences were noted for OSS and PICO
      comparisons, or for any products regarding polyp or adenoma detection rates.
      CONCLUSIONS: Critical heterogeneity precludes firm conclusion on the impact of
      adjuvants with existing bowel preparations. Additional research is required to
      better characterize the methods of administration and resulting roles of
      adjuvants in an era of split-dosing.

PMID- 29065438
TI  - Surveillance colonoscopy in Austria: Are we following the guidelines?
AB  - BACKGROUND AND STUDY AIM: The European guidelines for quality assurance in
      colorectal cancer screening and diagnosis contain postpolypectomy surveillance
      recommendations. They recommend follow-up intervals depending on the findings at
      index colonoscopy, and divide patients into a low-, intermediate- or high-risk
      group. The aim of this study was to assess the adherence of Austrian endoscopists
      to the European guidelines and to determine whether sending a reminder letter
      resulted in better adherence. METHODS: A single reminder letter containing the
      guidelines was sent to all endoscopists who participated in the Certificate of
      Quality for Screening Colonoscopy program in Austria. Adherence was assessed
      before and after the letter had been sent. Factors associated with adherence were
      investigated. RESULTS: We found poor baseline adherence to the guidelines. After
      the reminder letter, the adherence slightly improved in the low-risk group, but
      did not change in the intermediate-risk or high-risk groups. An adenoma detection
      rate of at least 20 % was associated with higher adherence rates. Generally,
      internists and hospitals showed better adherence compared with surgeons and
      private practices, respectively, both before and after the reminder letter.
      CONCLUSION: A single reminder letter was not enough to improve the poor adherence
      to the European postpolypectomy surveillance guidelines. Thus, future studies are
      required to identify and eliminate all factors responsible for nonadherence to
      postpolypectomy guidelines in order to reach the goal of a safe, effective, and
      cost-effective colorectal cancer prevention tool in the near future.

PMID- 29065441
TI  - Harmonization of laboratory results by data adjustment in multicenter clinical
      trials.
AB  - BACKGROUND/AIMS: In multicenter clinical trials, laboratory tests are performed
      in the laboratory of each center, mostly using different measuring methodologies.
      The purpose of this study was to evaluate coefficients of variation (CVs) of
      laboratory results produced by various measuring methods and to determine whether
      mathematical data adjustment could achieve harmonization between the methods.
      METHODS: We chose 10 clinical laboratories, including Green Cross Laboratories
      (GC Labs), the central laboratory, for the measurement of total cholesterol, high
      density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL
      C), serum triglycerides, creatinine, and glucose. The serum panels made with
      patient samples referred to GC Labs were sent to the other laboratories. Twenty
      serum samples for each analyte were prepared, sent frozen, and analyzed by each
      participating laboratory. RESULTS: All methods used by participating laboratories
      for the six analytes had traceability by reference materials and methods. When
      the results from the nine laboratories were compared with those from GC Labs, the
      mean CVs for total cholesterol, HDL-C, LDL-C, and glucose analyzed using the same
      method were 1.7%, 3.7%, 4.3%, and 1.7%, respectively; and those for triglycerides
      and creatinine analyzed using two different methods were 4.5% and 4.48%,
      respectively. After adjusting data using Deming regression, the mean CV were
      0.7%, 1.4%, 1.8%, 1.4%, 1.6%, and 0.8% for total cholesterol, HDL-C, LDL-C,
      triglyceride, creatinine, and glucose, respectively. CONCLUSION: We found that
      more comparable results can be produced by laboratory data harmonization using
      commutable samples. Therefore, harmonization efforts should be undertaken in
      multicenter trials for accurate data analysis (CRIS number; KCT0001235).

PMID- 29065443
TI  - New Insights into "Permeability" as in the Enhanced Permeability and Retention
      Effect of Cancer Nanotherapeutics.

PMID- 29065440
TI  - Individual and combined effects of hepatitis B surface antigen level and viral
      load on liver cancer risk.
AB  - BACKGROUND: Hepatitis B surface antigen (HBsAg) and viral load are both hallmarks
      of hepatitis B virus (HBV) infection and have potential to stratify liver cancer
      risk. METHODS: We carried out a nested case-control study including 211 liver
      cancer cases and 221 controls who were seropositive for HBsAg within two
      population-based cohorts in Shanghai. Logistic regression was performed to
      estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Risk
      of liver cancer was positively related to increasing levels of HBV-DNA and HBsAg
      in dose-response manners. Compared with subjects with HBV-DNA < 2000 IU/ml, the
      adjusted ORs increased from 2.11 (95%CI: 0.99-4.50) to 10.47 (95%CI: 5.06-21.68)
      for those with HBV-DNA level at 2000-19 999 to >= 20 000 IU/ml. Compared with
      subjects at a low level of HBsAg (0.05-99 IU/ml), the adjusted ORs increased from
      1.82 (95%CI: 0.90-3.68) to 2.21 (95%CI: 1.10-4.43) for those with HBsAg level at
      100-999 to >= 1000 IU/ml. Compared with subjects with HBV-DNA < 2000 IU/ml and
      HBsAg < 100 IU/ml, the adjusted ORs were increased from 2.20 (95%CI: 1.07-4.49)
      for those with HBV-DNA < 2000 and HBsAg >= 100 IU/ml to 6.94 (95%CI: 3.39-14.23)
      for those with HBV-DNA >= 2000 IU/ml and HBsAg < 1000 IU/ml, and 16.15 (95%CI:
      7.60-34.32) for those with HBV-DNA >= 2000 IU/ml and HBsAg >= 1000 IU/ml.
      CONCLUSION: Elevated levels of HBV-DNA and HBsAg are associated with increased
      risks of liver cancer. Chronic HBsAg carriers may be suggested to simultaneously
      lower the viral load to < 2000 IU/ml and HBsAg level to < 100 IU/ml to lower
      their liver cancer risk.

PMID- 29065444
TI  - Direct Effects of the Home, School, and Consumer Food Environments on the
      Association between Food Purchasing Patterns and Dietary Intake among Rural
      Adolescents in Kentucky and North Carolina, 2017.
AB  - Background: Obesity rates are higher among rural versus urban adolescents. To
      examine possible mechanisms for the rural-urban adolescent obesity disparity, we
      examined the direct and indirect effects of food purchasing patterns, and the
      home, school, and consumer food environments on dietary intake among rural
      adolescents. Methods: A baseline survey was conducted among adolescents in eight
      rural high schools (four in Eastern Kentucky, and four in Eastern North
      Carolina). Participants answered questions about food purchasing patterns,
      dietary intake, home food availability, and demographics. The school and consumer
      food environments were assessed using validated measures from the School Meals
      Cost Study (United States Department of Agriculture-Mathematica) and the
      Nutrition Environment Measurement Survey for Stores, Restaurants, and Corner
      Stores. Results: Of 432 adolescents, 55% were normal weight, 24% were overweight,
      and 21% were obese. There was a direct association between unhealthy food
      purchasing patterns (shopping frequently at gas stations, fast food, and dollar
      stores) and consuming more added sugars, when compared to those with a healthy
      shopping pattern (shopping less frequently at gas stations, fast food, and dollar
      stores) [Odds Ratio = 2.41 (95% CI (confidence interval) 0.99, 3.82)]. Those who
      reported always having fruits and vegetables in the home consumed more servings
      of fruits and vegetables [OR = 0.31 cups (95% CI 0.22, 0.44)] compared to those
      who reported never having fruits and vegetables in the home. Adolescents
      attending a school with a low healthy food availability score consumed fewer
      servings of fruits and vegetables [-0.001 (95% CI -0.001, 0.0001)] compared to
      those attending a school with a high healthy food availability score.
      Conclusions: There are direct associations between food purchasing patterns, the
      home and school food environments, and dietary intake among rural adolescents.
      These cross-sectional results informed the development of the "Go Big and Bring
      it Home" program, a text messaging intervention to improve adolescents' fruit,
      vegetable, and healthy beverage intake.

PMID- 29065445
TI  - Towards Better Understanding of Pea Seed Dormancy Using Laser
      Desorption/Ionization Mass Spectrometry.
AB  - Seed coats of six pea genotypes contrasting in dormancy were studied by laser
      desorption/ionization mass spectrometry (LDI-MS). Multivariate statistical
      analysis discriminated dormant and non-dormant seeds in mature dry state.
      Separation between dormant and non-dormant types was observed despite important
      markers of particular dormant genotypes differ from each other. Normalized
      signals of long-chain hydroxylated fatty acids (HLFA) in dormant JI64 genotype
      seed coats were significantly higher than in other genotypes. These compounds
      seem to be important markers likely influencing JI64 seed imbibition and
      germination. HLFA importance was supported by study of recombinant inbred lines
      (JI64xJI92) contrasting in dormancy but similar in other seed properties.
      Furthemore HLFA distribution in seed coat was studied by mass spectrometry
      imaging. HLFA contents in strophiole and hilum are significantly lower compared
      to other parts indicating their role in water uptake. Results from LDI-MS
      experiments are useful in understanding (physical) dormancy (first phases of
      germination) mechanism and properties related to food processing technologies
      (e.g., seed treatment by cooking).

PMID- 29065446
TI  - The Roles of Matricellular Proteins in Oncogenic Virus-Induced Cancers and Their
      Potential Utilities as Therapeutic Targets.
AB  - Matricellular proteins differ from other classical extracellular matrix proteins;
      for instance, they are transiently expressed as soluble proteins rather than
      being constitutively expressed in pathological conditions, such as acute viral
      infections. Accumulating studies have revealed that matricellular proteins,
      including osteopontin and tenascin-C, both of which interact with integrin
      heterodimers, are involved in inflammatory diseases, autoimmune disorders, and
      cancers. The concentrations of these matricellular proteins are elevated in the
      plasma of patients with certain types of cancers, indicating that they play
      important roles in oncogenesis. Chronic viral infections are associated with
      certain cancers, which are distinct from non-viral cancers. Viral oncogenes play
      critical roles in the development and progression of such cancers. It is vital to
      investigate the mechanisms of tumorigenesis and, particularly, the mechanism by
      which viral proteins induce tumor progression. Viral proteins have been shown to
      influence not only the viral-infected cancer cells, but also the stromal cells
      and matricellular proteins that constitute the extracellular matrix that
      surrounds tumor tissues. In this review, we summarize the recent progress on the
      involvement of matricellular proteins in oncogenic virus-induced cancers to
      elucidate the mechanism of oncogenesis and consider the possible role of
      matricellular proteins as therapeutic targets in virus-induced cancers.

PMID- 29065447
TI  - Analysis of Predictive Factors on Minors' Mental Health According to the Spanish
      National Health Survey.
AB  - Research on minors' mental health is an increasingly developing area. Given the
      increased prevalence of disorders, it seems necessary to analyze the factors that
      can affect poor mental health. This study analyzes the influence of occupational
      class, educational level, age, sex and perceived mental health of Spanish
      children, which is measured through the Strengths and Difficulties Questionnaire.
      The sample consists of 3599 minors between 4 and 14 years old, who were
      interviewed through the Spanish National Health Survey 2011. Our results
      indicating the significant (p < 0.05) relationship between mental health,
      occupational class (OR 0.533) and minors' health in the last year (OR 0.313) are
      shown. However, gender (OR 1.187) and educational level of Pre-School Education
      in relation to Secondary Education (OR 1.174) and Primary Education (OR 0.996) do
      not generate significant differences. In conclusion, we consider it necessary to
      design and implement public policies aimed at improving the care system for
      children who have had poor or regular health in the last year, and whose parents
      are positioned in the lowest part of the occupational scale.

PMID- 29065449
TI  - Chronic Venous Insufficiency: Transforming Growth Factor-beta Isoforms and
      Soluble Endoglin Concentration in Different States of Wound Healing.
AB  - Venous leg ulcer (VLU) is a huge healthcare problem with poorly understood
      pathophysiology. Transforming growth factor-beta (TGF-beta) and endoglin (Eng),
      are inflammatory and wound healing mediators. Eng, co-receptor for TGF-beta type
      II receptors, may be cleaved forming soluble Eng (sEng), antagonizing TGF-beta
      signaling, a crucial process in vascular pathologies. We evaluated the
      accumulation in wound fluid (WF) of TGF-beta isoforms and sEng in healing stages,
      showing the effects of sulodexide treatments, a glycosaminoglycan with clinical
      efficacy in VLU healing. Patients with inflammatory (Infl) and granulating (Gran)
      VLU were recruited. WFs and THP-1 monocytes exposed to Infl and Gran WF
      (treated/untreated with sulodexide) were analyzed for TGF-beta isoforms and sEng
      by multiplex immunoassay. In both Infl and Gran WF, TGF-beta1 and beta2 were
      similar; TGF-beta3 was significantly increased in Infl compared to Gran WFs (p =
      0.033). sEng was significantly elevated in Gran compared to Infl WFs (p = 0.002).
      In THP-1 monocytes there was a significant increase in sEng after co-treatment of
      WF and sulodexide. The increase in TGF-beta3 found in Infl WF highlights its
      negative effect on wound healing, while the increased levels of sEng in Gran WF
      affects the leukocyte adhesion/transmigration through the endothelium, reducing
      the inflammatory response and favoring the wound healing. Glycosaminoglycan
      sulodexide potentiates the effects of sEng release from monocyte, representing an
      important therapeutic option for wound healing.

PMID- 29065448
TI  - Phytotherapeutics: The Emerging Role of Intestinal and Hepatocellular
      Transporters in Drug Interactions with Botanical Supplements.
AB  - In herbalism, botanical supplements are commonly believed to be safe remedies,
      however, botanical supplements and dietary ingredients interact with transport
      and metabolic processes, affecting drug disposition. Although a large number of
      studies have described that botanical supplements interfere with drug metabolism,
      the mode of their interaction with drug transport processes is not well
      described. Such interactions may result in serious undesired effects and changed
      drug efficacy, therefore, some studies on interaction between botanical
      supplement ingredients and drug transporters such as P-gp and OATPs are described
      here, suggesting that the interaction between botanical supplements and the drug
      transporters is clinically significant.

PMID- 29065450
TI  - Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin
      Proteasome System.
AB  - Gammaherpesviruses like Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated
      herpesvirus (KSHV) subvert the ubiquitin proteasome system for their own benefit
      in order to facilitate viral gene expression and replication. In particular,
      viral tegument proteins that share sequence homology to the formylglycineamide
      ribonucleotide amidotransferase (FGARAT, or PFAS), an enzyme in the cellular
      purine biosynthesis, are important for disrupting the intrinsic antiviral
      response associated with Promyelocytic Leukemia (PML) protein-associated nuclear
      bodies (PML-NBs) by proteasome-dependent and independent mechanisms. In addition,
      all herpesviruses encode for a potent ubiquitin protease that can efficiently
      remove ubiquitin chains from proteins and thereby interfere with several
      different cellular pathways. In this review, we discuss mechanisms and functional
      consequences of virus-induced ubiquitination and deubiquitination for early
      events in gammaherpesviral infection.

PMID- 29065451
TI  - Inhibitory Effects of Siegesbeckia orientalis Extracts on Advanced Glycation End
      Product Formation and Key Enzymes Related to Metabolic Syndrome.
AB  - Metabolic syndrome typically includes Type 2 diabetes associated with
      hyperglycemia, central obesity, dyslipidemia and hypertension. It is highly
      related to oxidative stress, formation of advanced glycated end products (AGEs)
      and key enzymes, such as carbohydrate digesting enzymes like pancreatic alpha
      amylase and intestinal alpha-glucosidase, pancreatic lipase and angiotensin I
      converting enzyme (ACE). This study used an in vitro approach to assess the
      potential of four extracts of Siegesbeckia orientalis linne on key enzymes
      relevant to metabolic syndrome. In this research, S. orientailis was firstly
      extracted by ethanol. The ethanol extract (SE) was then partitioned sequentially
      with hexane, ethyl acetate and methanol, and these extracts were named SE-Hex, SE
      EA and SE-MeOH, respectively. The experimental results showed that SE-EA had the
      highest total phenolic content (TPC, 76.9 +/- 1.8 mg/g) and the total flavonoids
      content (TFC, 5.3 +/- 0.3 mg/g). This extract exhibited the most significant
      antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8
      +/- 2.4 MUg/mL), ABTS radical-scavenging capacity (IC50 = 13.9 +/- 1.5 MUg/mL)
      and reducing power. For anti-glycation activities, SE-EA showed the best results
      in the inhibition of AGEs, as well as inhibitory activities against alpha
      glucosidase (IC50 = 362.3 +/- 9.2 MUg/mL) and alpha-amylase (IC50 = 119.0 +/-
      17.7 MUg/mL). For anti-obesity activities, SE-EA indicated the highest
      suppression effect on pancreatic lipase (IC50 = 3.67 +/- 0.52 mg/mL). Finally,
      for anti-hypertension activity, SE-EA also demonstrated the strongest inhibitory
      activity on ACE (IC50 = 626.6 +/- 15.0 MUg/mL). Close relationships were observed
      among the parameters of TPC, antioxidant activities, inhibitory activities on
      alpha-amylase, alpha-glucosidase, lipase and ACE (R > 0.9). Moderate correlations
      were found among the parameters of TFC, antioxidant activities, and suppression
      of dicarbonyl compounds formation (R = 0.5-0.9). Taken together these in vitro
      studies reveal the therapeutic potential of SE-EA extract in the prevention and
      treatment of metabolic disorders.

PMID- 29065452
TI  - Morphometric Modifications in Canthon quinquemaculatus Castelnau 1840
      (Coleoptera: Scarabaeinae): Sublethal Effects of Transgenic Maize?
AB  - The effects of transgenic compounds on non-target organisms remain poorly
      understood, especially in native insect species. Morphological changes (e.g.,
      changes in body size and shape) may reflect possible responses to environmental
      stressors, like transgenic toxins. The dung beetle Canthon quinquemaculatus
      (Coleoptera: Scarabaeinae) is a non-target species found in transgenic crops. We
      evaluated whether C. quinquemaculatus individuals inhabiting corn fields
      cultivated with different seed types (conventional, creole and transgenic)
      present modifications in body shape compared to individuals inhabiting adjacent
      native forest fragments. We collected C. quinquemaculatus specimens across an
      agricultural landscape in southern Brazil, during the summer of 2015. Six
      populations were sampled: three maize crop populations each under a different
      seed type, and three populations of adjacent forests. After sampling, specimens
      were subjected to morphometric analyses to discover differences in body shape. We
      chose fifteen landmarks to describe body shape, and morphometric data were tested
      with Procrustes ANOVA and Discriminant Analysis. We found that body shape did not
      differ between individuals collected in conventional and creole crops with their
      respective adjacent forests (p > 0.05); however, transgenic crop populations
      differed significantly from those collected in adjacent forests (p < 0.05).
      Insects in transgenic maize are more oval and have a retraction in the abdominal
      region, compared with the respective adjacent forest, this result shows the
      possible effect of transgenic crops on non-target species. This may have
      implications for the ecosystem service of organic matter removal, carried out by
      these organisms.

PMID- 29065453
TI  - An Update on the Sociomicrobiology of Quorum Sensing in Gram-Negative Biofilm
      Development.
AB  - Bacteria are social creatures that are able to interact and coordinate behaviors
      with each other in a multitude of ways. The study of such group behaviors in
      microbes was coined "sociomicrobiology" in 2005. Two such group behaviors in
      bacteria are quorum sensing (QS) and biofilm formation. At a very basic level, QS
      is the ability to sense bacterial density via cell-to-cell signaling using self
      produced signals called autoinducers, and biofilms are aggregates of cells that
      are attached to one another via a self-produced, extracellular matrix. Since
      cells in biofilm aggregates are in close proximity, biofilms represent an
      ecologically relevant environment for QS. While QS is known to affect biofilm
      formation in both Gram-negative and Gram-positive species, in this review, we
      will focus exclusively on Gram-negative bacteria, with an emphasis on Pseudomonas
      aeruginosa. We will begin by describing QS systems in P. aeruginosa and how they
      affect P. aeruginosa biofilm formation. We then expand our review to other Gram
      negative bacteria and conclude with interesting questions with regard to the
      effect of biofilms on QS.

PMID- 29065454
TI  - Perceptions of Risk Stratification Workflows in Primary Care.
AB  - Risk stratification (RS) in primary care is frequently used by policy-makers,
      payers, and health systems; the process requires risk assessment for adverse
      health outcomes across a population to assign patients into risk tiers and allow
      care management (CM) resources to be targeted effectively. Our objective was to
      understand the approach to and perception of RS in primary care practices. An
      online survey was developed, tested, and administered to 148 representatives of
      37 primary care practices engaged in RS varying in size, location and ownership.
      The survey assessed practices' approach to, perception of, and confidence in RS,
      and its effect on subsequent CM activities. We examined psychometric properties
      of the survey to determine validity and conducted chi-square analyses to
      determine the association between practice characteristics and confidence and
      agreement with risk scores. The survey yielded a 68% response rate (100
      respondents). Overall, participants felt moderately confident in their risk
      scores (range 41-53.8%), and moderately to highly confident in their subsequent
      CM workflows (range 46-68%). Respondents from small and independent practices
      were more likely to have higher confidence and agreement with their RS approaches
      and scores (p < 0.01). Confidence levels were highest, however, when practices
      incorporated human review into their RS processes (p < 0.05). This trend was not
      affected by respondents' professional roles. Additional work from a broad mixed
      methods effort will add to our understanding of RS implementation processes and
      outcomes.

PMID- 29065456
TI  - The Operophtera brumata Nucleopolyhedrovirus (OpbuNPV) Represents an Early,
      Divergent Lineage within Genus Alphabaculovirus.
AB  - Operophtera brumata nucleopolyhedrovirus (OpbuNPV) infects the larvae of the
      winter moth, Operophtera brumata. As part of an effort to explore the pesticidal
      potential of OpbuNPV, an isolate of this virus from Massachusetts (USA)-OpbuNPV
      MA-was characterized by electron microscopy of OpbuNPV occlusion bodies (OBs) and
      by sequencing of the viral genome. The OBs of OpbuNPV-MA consisted of irregular
      polyhedra and contained virions consisting of a single rod-shaped nucleocapsid
      within each envelope. Presumptive cypovirus OBs were also detected in sections of
      the OB preparation. The OpbuNPV-MA genome assembly yielded a circular contig of
      119,054 bp and was found to contain little genetic variation, with most
      polymorphisms occurring at a frequency of < 6%. A total of 130 open reading
      frames (ORFs) were annotated, including the 38 core genes of Baculoviridae, along
      with five homologous repeat (hr) regions. The results of BLASTp and phylogenetic
      analysis with selected ORFs indicated that OpbuNPV-MA is not closely related to
      other alphabaculoviruses. Phylogenies based on concatenated core gene amino acid
      sequence alignments placed OpbuNPV-MA on a basal branch lying outside other
      alphabaculovirus clades. These results indicate that OpbuNPV-MA represents a
      divergent baculovirus lineage that appeared early during the diversification of
      genus Alphabaculovirus.

PMID- 29065457
TI  - Metacognitive Precursors: An Analysis in Children with Different Disabilities.
AB  - The analysis of Metacognitive skills is a key element to guide the learning
      process. Current research has shown the initiation of these skills from an early
      age. The present study had two aims: (1) to validate a Scale Measuring Precursor
      Metacognitive Skills (SMPMS) in children with diverse disabilities, and (2) to
      study possible significant different between different disabilities in precursor
      metacognitive skill use. We worked with 87 children with different disabilities,
      with an average age range of 24-37 months. The results have shown high indicators
      of reliability and validity of the SMPMS. We isolated two factors related to
      cognitive and metacognitive and self-regulation skills response to an adult. We
      also found significant differences in the acquisition of metacognitive and self
      regulation skills among children with global developmental retardation as
      compared to children with expressive language and comprehension disability.

PMID- 29065455
TI  - Tubulin Post-Translational Modifications and Microtubule Dynamics.
AB  - Microtubules are hollow tube-like polymeric structures composed of alpha,beta
      tubulin heterodimers. They play an important role in numerous cellular processes,
      including intracellular transport, cell motility and segregation of the
      chromosomes during cell division. Moreover, microtubule doublets or triplets form
      a scaffold of a cilium, centriole and basal body, respectively. To perform such
      diverse functions microtubules have to differ in their properties. Post
      translational modifications are one of the factors that affect the properties of
      the tubulin polymer. Here we focus on the direct and indirect effects of post
      translational modifications of tubulin on microtubule dynamics.

PMID- 29065459
TI  - Investigation of Temperature Sensitivity of a Polymer-Overlaid Microfiber Mach
      Zehnder Interferometer.
AB  - The temperature sensitivity of the free spectral range (FSR) for a polymer
      overlaid microfiber Mach-Zehnder interferometer (MZI) is investigated both
      theoretically and experimentally. The waist diameter of the optical microfiber
      can be controlled to alter the thermal expansion and optic properties of the
      polymer-coated MZI. Inserting an optical microfiber with a strong evanescent
      field into the MZI, a low index polymer with high thermal characteristics is
      deposited on the surface of the microfibers to realize a polymer-overlaid
      microfiber MZI. It was found that the thermal expansion factor in the proposed
      MZI plays an important role in the temperature sensitivity of the FSR. The
      temperature sensitivity of the polymer-overlaid microfiber MZI is improved, which
      is measured to be -8.29 nm/ degrees C at 25  degrees C. The optical transmission
      spectrum of the polymer-overlaid microfiber MZI is converted to the spatial
      frequency spectrum via fast Fourier transform. The temperature sensitivity of the
      spatial frequency in the proposed polymer-overlaid MZI is estimated to be 18.31
      pm-1  degrees C-1, which is 17 times higher than that of the microfiber MZI
      without polymer coating (1.04 pm-1  degrees C-1).

PMID- 29065458
TI  - Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation
      Revealed by CRISPR/Cas9-Mediated Mouse Models.
AB  - A recent genetic analysis of infertile globozoospermic patients identified
      causative mutations in three genes: a protein interacting with C kinase 1
      (PICK1), dpy 19-like 2 (DPY19L2), and spermatogenesis associated 16 (SPATA16).
      Although mouse models have clarified the physiological functions of Pick1 and
      Dpy19l2 during spermatogenesis, Spata16 remains to be determined. Globozoospermic
      patients carried a homozygous point mutation in SPATA16 at 848G->A/R283Q. We
      generated CRISPR/Cas9-mediated mutant mice with the same amino acid substitution
      in the fourth exon of Spata16 to analyze the mutation site at R284Q, which
      corresponded with R283Q of mutated human SPATA16. We found that the point
      mutation in Spata16 was not essential for male fertility; however, deletion of
      the fourth exon of Spata16 resulted in infertile male mice due to spermiogenic
      arrest but not globozoospermia. This study demonstrates that Spata16 is
      indispensable for male fertility in mice, as well as in humans, as revealed by
      CRISPR/Cas9-mediated mouse models.

PMID- 29065461
TI  - Command Disaggregation Attack and Mitigation in Industrial Internet of Things.
AB  - A cyber-physical attack in the industrial Internet of Things can cause severe
      damage to physical system. In this paper, we focus on the command disaggregation
      attack, wherein attackers modify disaggregated commands by intruding command
      aggregators like programmable logic controllers, and then maliciously manipulate
      the physical process. It is necessary to investigate these attacks, analyze their
      impact on the physical process, and seek effective detection mechanisms. We
      depict two different types of command disaggregation attack modes: (1) the
      command sequence is disordered and (2) disaggregated sub-commands are allocated
      to wrong actuators. We describe three attack models to implement these modes with
      going undetected by existing detection methods. A novel and effective framework
      is provided to detect command disaggregation attacks. The framework utilizes the
      correlations among two-tier command sequences, including commands from the output
      of central controller and sub-commands from the input of actuators, to detect
      attacks before disruptions occur. We have designed components of the framework
      and explain how to mine and use these correlations to detect attacks. We present
      two case studies to validate different levels of impact from various attack
      models and the effectiveness of the detection framework. Finally, we discuss how
      to enhance the detection framework.

PMID- 29065460
TI  - Flotation Assembly of Large-Area Ultrathin MWCNT Nanofilms for Construction of
      Bioelectrodes.
AB  - We report a simple, versatile, and rapid method for the fabrication of optically
      transparent large-area carbon nanotube (CNT) films via flotation assembly. After
      solvent-induced assembly, floating films were transferred to a flat supporting
      substrate to form conductive and transparent CNT film electrodes. The resulting
      electrodes, with uniform 40 +/- 20 nm multi-walled CNT (MWCNT) layers, were
      characterized by electrochemical and microscopy methods. The flotation method
      does not require specialized thin-film instrumentation and avoids the need for
      surfactants and pre-oxidized CNTs which can hamper electrochemical performance. A
      proof-of-concept nanostructured bioelectrode demonstrating high sensitivity for
      glucose was developed with an electropolymerized poly(pyrene-adamantane) layer
      for host-guest immobilization of active beta-cyclodextrin tagged GOx enzymes. The
      polymer provides pyrene groups for cross-linking to CNTs and pendant adamantane
      groups for binding the beta-cyclodextrin groups of the tagged enzyme. This
      demonstration offers a new approach for the preparation of stable and transparent
      CNT film electrodes with attractive electrochemical properties towards future
      photobio- and bio-electrochemical fuel cells, electrochemical sensors, and
      electroanalysis.

PMID- 29065462
TI  - Cinnamic Acid Analogs as Intervention Catalysts for Overcoming Antifungal
      Tolerance.
AB  - Disruption of fungal cell wall should be an effective intervention strategy.
      However, the cell wall-disrupting echinocandin drugs, such as caspofungin (CAS),
      cannot exterminate filamentous fungal pathogens during treatment. For potency
      improvement of cell wall-disrupting agents (CAS, octyl gallate (OG)), antifungal
      efficacy of thirty-three cinnamic acid derivatives was investigated against
      Saccharomyces cerevisiaeslt2Delta, bck1Delta, mutants of the mitogen-activated
      protein kinase (MAPK), and MAPK kinase kinase, respectively, in cell wall
      integrity system, and glr1Delta, mutant of CAS-responsive glutathione reductase.
      Cell wall mutants were highly susceptible to four cinnamic acids (4-chloro-alpha
      methyl-, 4-methoxy-, 4-methyl-, 3-methylcinnamic acids), where 4-chloro-alpha
      methyl- and 4-methylcinnamic acids possessed the highest activity. Structure
      activity relationship revealed that 4-methylcinnamic acid, the deoxygenated
      structure of 4-methoxycinnamic acid, overcame tolerance of glr1Delta to 4
      methoxycinnamic acid, indicating the significance of para substitution of methyl
      moiety for effective fungal control. The potential of compounds as
      chemosensitizers (intervention catalysts) to cell wall disruptants (viz., 4
      chloro-alpha-methyl- or 4-methylcinnamic acids + CAS or OG) was assessed
      according to Clinical Laboratory Standards Institute M38-A. Synergistic
      chemosensitization greatly lowers minimum inhibitory concentrations of the co
      administered drug/agents. 4-Chloro-alpha-methylcinnamic acid further overcame
      fludioxonil tolerance of Aspergillus fumigatus antioxidant MAPK mutants
      (sakADelta, mpkCDelta). Collectively, 4-chloro-alpha-methyl- and 4-methylcinnamic
      acids possess chemosensitizing capability to augment antifungal efficacy of
      conventional drug/agents, thus could be developed as target-based (i.e., cell
      wall disruption) intervention catalysts.

PMID- 29065464
TI  - To Spray or Not to Spray: A Decision Analysis of Coffee Berry Borer in Hawaii.
AB  - Integrated pest management strategies were adopted to combat the coffee berry
      borer (CBB) after its arrival in Hawaii in 2010. A decision tree framework is
      used to model the CBB integrated pest management recommendations, for potential
      use by growers and to assist in developing and evaluating management strategies
      and policies. The model focuses on pesticide spraying (spray/no spray) as the
      most significant pest management decision within each period over the entire crop
      season. The main result from the analysis suggests the most important parameter
      to maximize net benefit is to ensure a low initial infestation level. A second
      result looks at the impact of a subsidy for the cost of pesticides and shows a
      typical farmer receives a positive net benefit of $947.17. Sensitivity analysis
      of parameters checks the robustness of the model and further confirms the
      importance of a low initial infestation level vis-a-vis any level of subsidy. The
      use of a decision tree is shown to be an effective method for understanding
      integrated pest management strategies and solutions.

PMID- 29065463
TI  - Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of
      Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat.
AB  - Among diabetes patients, ophthalmological complications are very frequent. High
      blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute
      significantly to the severity of retinopathies. Diabetic retinopathy is among the
      leading causes of blindness. Our study demonstrates the effect of sour cherry
      seed extract (SCSE) on blood glucose and function of the retina with
      electroretinography (ERG) in a diabetic setting with or without ischemia
      reperfusion (I/R) injury in Zucker Diabetic Fatty (ZDF) rats. Our results prove
      that the SCSE has a retinoprotective effect in diabetic rats: according to ERG
      measurements, SCSE treatment mitigated the retinal function-damaging effect of
      diabetes, and proved to be protective in the diabetic eye against ischemia
      reperfusion injuries of the retina. Outcomes suggest that the protective effects
      of SCSE may occur through several pathways, including HO-1 dependent mechanisms.
      The observation that SCSE treatment decreases blood glucose is also novel. These
      findings offer the possibility for development of novel therapeutic strategies
      utilizing this emerging functional food, in particular in the prevention of
      conditions resulting from high blood glucose or I/R injury, such as deterioration
      of retinal microcirculation.

PMID- 29065465
TI  - Assembly of 1D Granular Structures from Sulfonated Polystyrene Microparticles.
AB  - Being able to systematically modify the electric properties of nano- and
      microparticles opens up new possibilities for the bottom-up fabrication of
      advanced materials such as the fabrication of one-dimensional (1D) colloidal and
      granular materials. Fabricating 1D structures from individual particles offers
      plenty of applications ranging from electronic sensors and photovoltaics to
      artificial flagella for hydrodynamic propulsion. In this work, we demonstrate the
      assembly of 1D structures composed of individual microparticles with modified
      electric properties, pulled out of a liquid environment into air. Polystyrene
      particles were modified by sulfonation for different reaction times and
      characterized by dielectric spectroscopy and dipolar force measurements. We found
      that by increasing the sulfonation time, the values of both electrical
      conductivity and dielectric constant of the particles increase, and that the
      relaxation frequency of particle electric polarization changes, causing the
      measured dielectric loss of the particles to shift towards higher frequencies. We
      attributed these results to water adsorbed at the surface of the particles. With
      sulfonated polystyrene particles exhibiting a range of electric properties, we
      showed how the electric properties of individual particles influence the
      formation of 1D structures. By tuning applied voltage and frequency, we were able
      to control the formation and dynamics of 1D structures, including chain bending
      and oscillation.

PMID- 29065466
TI  - Collagen-Based Medical Device as a Stem Cell Carrier for Regenerative Medicine.
AB  - Maintenance of mesenchymal stem cells (MSCs) requires a tissue-specific
      microenvironment (i.e., niche), which is poorly represented by the typical
      plastic substrate used for two-dimensional growth of MSCs in a tissue culture
      flask. The objective of this study was to address the potential use of collagen
      based medical devices (HEMOCOLLAGENE(r), Saint-Maur-des-Fosses, France) as
      mimetic niche for MSCs with the ability to preserve human MSC stemness in vitro.
      With a chemical composition similar to type I collagen, HEMOCOLLAGENE(r) foam
      presented a porous and interconnected structure (>90%) and a relative low elastic
      modulus of around 60 kPa. Biological studies revealed an apparently inert
      microenvironment of HEMOCOLLAGENE(r) foam, where 80% of cultured human MSCs
      remained viable, adopted a flattened morphology, and maintained their
      undifferentiated state with basal secretory activity. Thus, three-dimensional
      HEMOCOLLAGENE(r) foams present an in vitro model that mimics the MSC niche with
      the capacity to support viable and quiescent MSCs within a low stiffness collagen
      I scaffold simulating Wharton's jelly. These results suggest that haemostatic
      foam may be a useful and versatile carrier for MSC transplantation for
      regenerative medicine applications.

PMID- 29065467
TI  - Adaptive Microwave Staring Correlated Imaging for Targets Appearing in Discrete
      Clusters.
AB  - Microwave staring correlated imaging (MSCI) can achieve ultra-high resolution in
      real aperture staring radar imaging using the correlated imaging process (CIP)
      under all-weather and all-day circumstances. The CIP must combine the received
      echo signal with the temporal-spatial stochastic radiation field. However, a
      precondition of the CIP is that the continuous imaging region must be discretized
      to a fine grid, and the measurement matrix should be accurately computed, which
      makes the imaging process highly complex when the MSCI system observes a wide
      area. This paper proposes an adaptive imaging approach for the targets in
      discrete clusters to reduce the complexity of the CIP. The approach is divided
      into two main stages. First, as discrete clustered targets are distributed in
      different range strips in the imaging region, the transmitters of the MSCI emit
      narrow-pulse waveforms to separate the echoes of the targets in different strips
      in the time domain; using spectral entropy, a modified method robust against
      noise is put forward to detect the echoes of the discrete clustered targets,
      based on which the strips with targets can be adaptively located. Second, in a
      strip with targets, the matched filter reconstruction algorithm is used to locate
      the regions with targets, and only the regions of interest are discretized to a
      fine grid; sparse recovery is used, and the band exclusion is used to maintain
      the non-correlation of the dictionary. Simulation results are presented to
      demonstrate that the proposed approach can accurately and adaptively locate the
      regions with targets and obtain high-quality reconstructed images.

PMID- 29065469
TI  - Rapid Assessment of the Toxicity of Fungal Compounds Using Luminescent Vibrio
      qinghaiensis sp. Q67.
AB  - Most tropical fruits after harvest are very perishable because of fungal
      infection. Since some pathogenic fungi can produce hazardous compounds such as
      mycotoxins, novel rapid and effective methods to assess those hazardous compounds
      are urgently needed. Herein we report that Vibrio qinghaiensis sp. Q67, a
      luminescent bacterium, can be used to rapidly assess the toxicities of mycotoxins
      and cultures from mycotoxin-producing pathogens. A good correlation (R2 > 0.98)
      between concentrations of the mycotoxins (fumonisin B1, deoxynivalenol,
      zearalenone, ochratoxin A, patulin, and citrinin) and the luminous intensity of
      V. qinghaiensis sp. Q67 was obtained. Furthermore, significant correlations (R2 >
      0.96) between the amount of mycotoxin and the luminous intensity from the
      cultures of 10 major mycotoxin-producing pathogens were also observed. In
      addition, Fusarium proliferatum (half-maximal inhibitory concentration (IC50) =
      17.49%) exhibited greater luminescence suppression than Fusarium semitectum (IC50
      = 92.56%) or Fusarium oxysporum (IC50 = 28.61%), which was in agreement with the
      existing higher levels of fumonisin B1, fumonisin B2, and deoxynivalenol, which
      were measured by high-performance liquid chromatography-tandem mass spectrometry.
      These results suggest that V. qinghaiensis sp. Q67 is a promising alternative for
      the rapid evaluation of the toxicity of fungal mycotoxins.

PMID- 29065470
TI  - Separation and Analysis of Adherent and Non-Adherent Cancer Cells Using a Single
      Cell Microarray Chip.
AB  - A new single-cell microarray chip was designed and developed to separate and
      analyze single adherent and non-adherent cancer cells. The single-cell microarray
      chip is made of polystyrene with over 60,000 microchambers of 10 different size
      patterns (31-40 um upper diameter, 11-20 um lower diameter). A drop of suspension
      of adherent carcinoma (NCI-H1650) and non-adherent leukocyte (CCRF-CEM) cells was
      placed onto the chip, and single-cell occupancy of NCI-H1650 and CCRF-CEM was
      determined to be 79% and 84%, respectively. This was achieved by controlling the
      chip design and surface treatment. Analysis of protein expression in single NCI
      H1650 and CCRF-CEM cells was performed on the single-cell microarray chip by
      multi-antibody staining. Additionally, with this system, we retrieved positive
      single cells from the microchambers by a micromanipulator. Thus, this system
      demonstrates the potential for easy and accurate separation and analysis of
      various types of single cells.

PMID- 29065471
TI  - Association between Diet Quality and Adiposity in the Atlantic PATH Cohort.
AB  - The aim of this study was to examine diet quality among participants in the
      Atlantic Partnership for Tomorrow's Health (PATH) cohort and to assess the
      association with adiposity. Data were collected from participants (n = 23,768)
      aged 35-69 years that were residents of the Atlantic Canadian provinces. Both
      measured and self-reported data were used to examine adiposity (including body
      mass index (BMI), abdominal obesity, waist-to-hip ratio and fat mass) and food
      frequency questionnaires were used to assess diet quality. Overall, diet quality
      was statistically different among provinces. Of concern, participants across all
      the provinces reported consuming only 1-2 servings of vegetables and 1-2 servings
      fruit per day. However, participants also reported some healthy dietary choices
      such as consuming more servings of whole grains than refined grains, and eating
      at fast food restaurants <=1 per month. Significant differences in BMI, body
      weight, percentage body fat, and fat mass index were also observed among
      provinces. Adiposity measures were positively associated with consumption of
      meat/poultry, fish, snack food, sweeteners, diet soft drinks, and frequenting
      fast food restaurants, and inversely associated with consumption of whole grains
      and green tea. Although all four provinces are in the Atlantic region, diet
      quality vary greatly among provinces and are associated with adiposity.

PMID- 29065468
TI  - A Summary of New Findings on the Biological Effects of Selenium in Selected
      Animal Species-A Critical Review.
AB  - Selenium is an essential trace element important for many physiological
      processes, especially for the functions of immune and reproductive systems,
      metabolism of thyroid hormones, as well as antioxidant defense. Selenium
      deficiency is usually manifested by an increased incidence of retention of
      placenta, metritis, mastitis, aborts, lowering fertility and increased
      susceptibility to infections. In calves, lambs and kids, the selenium deficiency
      demonstrates by WMD (white muscle disease), in foals and donkey foals, it is
      associated with incidence of WMD and yellow fat disease, and in pigs it causes
      VESD (vitamin E/selenium deficiency) syndrome. The prevention of these health
      disorders can be achieved by an adequate selenium supplementation to the diet.
      The review summarizes the survey of knowledge on selenium, its biological
      significance in the organism, the impact of its deficiency in mammalian livestock
      (comparison of ruminants vs. non-ruminants, herbivore vs. omnivore) and
      possibilities of its peroral administration. The databases employed were as
      follows: Web of Science, PubMed, MEDLINE and Google Scholar.

PMID- 29065473
TI  - Reasoning and Knowledge Acquisition Framework for 5G Network Analytics.
AB  - Autonomic self-management is a key challenge for next-generation networks. This
      paper proposes an automated analysis framework to infer knowledge in 5G networks
      with the aim to understand the network status and to predict potential situations
      that might disrupt the network operability. The framework is based on the Endsley
      situational awareness model, and integrates automated capabilities for metrics
      discovery, pattern recognition, prediction techniques and rule-based reasoning to
      infer anomalous situations in the current operational context. Those situations
      should then be mitigated, either proactive or reactively, by a more complex
      decision-making process. The framework is driven by a use case methodology, where
      the network administrator is able to customize the knowledge inference rules and
      operational parameters. The proposal has also been instantiated to prove its
      adaptability to a real use case. To this end, a reference network traffic dataset
      was used to identify suspicious patterns and to predict the behavior of the
      monitored data volume. The preliminary results suggest a good level of accuracy
      on the inference of anomalous traffic volumes based on a simple configuration.

PMID- 29065474
TI  - Multivariable Analysis of Nutritional and Socio-Economic Profiles Shows
      Differences in Incident Anemia for Northern and Southern Jiangsu in China.
AB  - Anemia is a prevalent public health problem associated with nutritional and socio
      economic factors that contribute to iron deficiency. To understand the complex
      interplay of risk factors, we investigated a prospective population sample from
      the Jiangsu province in China. At baseline, three-day food intake was measured
      for 2849 individuals (20 to 87 years of age, mean age 47 +/- 14, range 20-87
      years, 64% women). At a five-year follow-up, anemia status was re-assessed for
      1262 individuals. The dataset was split and age-matched to accommodate cross
      sectional (n = 2526), prospective (n = 837), and subgroup designs (n = 1844). We
      applied a machine learning framework (self-organizing map) to define four
      subgroups. The first two subgroups were primarily from the less affluent North:
      the High Fibre subgroup had a higher iron intake (35 vs. 21 mg/day) and lower
      anemia incidence (10% vs. 25%) compared to the Low Vegetable subgroup. However,
      the predominantly Southern subgroups were surprising: the Low Fibre subgroup
      showed a lower anemia incidence (10% vs. 27%), yet also a lower iron intake (20
      vs. 28 mg/day) compared to the High Rice subgroup. These results suggest that
      interventions and iron intake guidelines should be tailored to regional,
      nutritional, and socio-economic subgroups.

PMID- 29065472
TI  - The Battle of RNA Synthesis: Virus versus Host.
AB  - Transcription control is the foundation of gene regulation. Whereas a cell is
      fully equipped for this task, viruses often depend on the host to supply tools
      for their transcription program. Over the course of evolution and adaptation,
      viruses have found diverse ways to optimally exploit cellular host processes such
      as transcription to their own benefit. Just as cells are increasingly understood
      to employ nascent RNAs in transcription regulation, recent discoveries are
      revealing how viruses use nascent RNAs to benefit their own gene expression. In
      this review, we first outline the two different transcription programs used by
      viruses, i.e., transcription (DNA-dependent) and RNA-dependent RNA synthesis.
      Subsequently, we use the distinct stages (initiation, elongation, termination) to
      describe the latest insights into nascent RNA-mediated regulation in the context
      of each relevant stage.

PMID- 29065476
TI  - Estimation of the Driving Style Based on the Users' Activity and Environment
      Influence.
AB  - New models and methods have been designed to predict the influence of the user's
      environment and activity information to the driving style in standard automotive
      environments. For these purposes, an experiment was conducted providing two types
      of analysis: (i) the evaluation of a self-assessment of the driving style; (ii)
      the prediction of aggressive driving style based on drivers' activity and
      environment parameters. Sixty seven h of driving data from 10 drivers were
      collected for analysis in this study. The new parameters used in the experiment
      are the car door opening and closing manner, which were applied to improve the
      prediction accuracy. An Android application called Sensoric was developed to
      collect low-level smartphone data about the users' activity. The driving style
      was predicted from the user's environment and activity data collected before
      driving. The prediction was tested against the actual driving style, calculated
      from objective driving data. The prediction has shown encouraging results, with
      precision values ranging from 0.727 up to 0.909 for aggressive driving
      recognition rate. The obtained results lend support to the hypothesis that user's
      environment and activity data could be used for the prediction of the aggressive
      driving style in advance, before the driving starts.

PMID- 29065475
TI  - Comparison of Summer and Winter Objectively Measured Physical Activity and
      Sedentary Behavior in Older Adults: Age, Gene/Environment Susceptibility
      Reykjavik Study.
AB  - In Iceland, there is a large variation in daylight between summer and winter. The
      aim of the study was to identify how this large variation influences physical
      activity (PA) and sedentary behavior (SB). Free living PA was measured by a waist
      worn accelerometer for one week during waking hours in 138 community-dwelling
      older adults (61.1% women, 80.3 +/- 4.9 years) during summer and winter months.
      In general, SB occupied about 75% of the registered wear-time and was highly
      correlated with age (beta = 0.36). Although the differences were small, more time
      was spent during the summer in all PA categories, except for the moderate-to
      vigorous PA (MVPA), and SB was reduced. More lifestyle PA (LSPA) was accumulated
      in >=5-min bouts during summer than winter, especially among highly active
      participants. This information could be important for policy makers and health
      professionals working with older adults. Accounting for seasonal difference is
      necessary in analyzing SB and PA data.

PMID- 29065477
TI  - Treatment of Severely Resorbed Maxilla Due to Peri-Implantitis by Guided Bone
      Regeneration Using a Customized Allogenic Bone Block: A Case Report.
AB  - The objective of this case report is to introduce a customized CAD/CAM freeze
      dried bone allograft (FDBA) block for its use in Guided Bone Regeneration (GBR)
      procedures for severely deficient maxillary bones. Additionally, a special newly
      developed remote incision technique is presented to avoid wound dehiscence. The
      results show optimal integration behavior of the FDBA block after six months and
      the formation of new vital bone. Thus, the results of the present case report
      confirm the use of the customized CAD/CAM bone block for augmentation of complex
      defects in the maxillary aesthetic zone as a successful treatment concept.

PMID- 29065478
TI  - Nitrogen-Rich Polyacrylonitrile-Based Graphitic Carbons for Hydrogen Peroxide
      Sensing.
AB  - Catalytic substrate, which is devoid of expensive noble metals and enzymes for
      hydrogen peroxide (H2O2), reduction reactions can be obtained via nitrogen doping
      of graphite. Here, we report a facile fabrication method for obtaining such
      nitrogen doped graphitized carbon using polyacrylonitrile (PAN) mats and its use
      in H2O2 sensing. A high degree of graphitization was obtained with a mechanical
      treatment of the PAN fibers embedded with carbon nanotubes (CNT) prior to the
      pyrolysis step. The electrochemical testing showed a limit of detection (LOD)
      0.609 uM and sensitivity of 2.54 uA cm-2 mM-1. The promising sensing performance
      of the developed carbon electrodes can be attributed to the presence of high
      content of pyridinic and graphitic nitrogens in the pyrolytic carbons, as
      confirmed by X-ray photoelectron spectroscopy. The reported results suggest that,
      despite their simple fabrication, the hydrogen peroxide sensors developed from
      pyrolytic carbon nanofibers are comparable with their sophisticated nitrogen
      doped graphene counterparts.

PMID- 29065480
TI  - Effect of Steam Deactivation Severity of ZSM-5 Additives on LPG Olefins
      Production in the FCC Process.
AB  - ZSM-5-containing catalytic additives are widely used in oil refineries to boost
      light olefin production and improve gasoline octanes in the Fluid Catalytic
      Cracking (FCC) process. Under the hydrothermal conditions present in the FCC
      regenerator (typically >700  degrees C and >8% steam), FCC catalysts and
      additives are subject to deactivation. Zeolites (e.g., Rare Earth USY in the base
      catalyst and ZSM-5 in Olefins boosting additives) are prone to dealumination and
      partial structural collapse, thereby losing activity, micropore surface area, and
      undergoing changes in selectivity. Fresh catalyst and additives are added at
      appropriate respective levels to the FCC unit on a daily basis to maintain
      overall targeted steady-state (equilibrated) activity and selectivity. To mimic
      this process under accelerated laboratory conditions, a commercial P/ZSM-5
      additive was hydrothermally equilibrated via a steaming process at two
      temperatures: 788  degrees C and 815  degrees C to simulate moderate and more
      severe equilibration industrial conditions, respectively. n-Dodecane was used as
      probe molecule and feed for micro-activity cracking testing at 560  degrees C to
      determine the activity and product selectivity of fresh and equilibrated P-doped
      ZSM-5 additives. The fresh/calcined P/ZSM-5 additive was very active in C12
      cracking while steaming limited its activity, i.e., at catalyst-to-feed (C/F)
      ratio of 1, about 70% and 30% conversion was obtained with the fresh and steamed
      additives, respectively. A greater activity drop was observed upon increasing the
      hydrothermal deactivation severity due to gradual decrease of total acidity and
      microporosity of the additives. However, this change in severity did not result
      in any selectivity changes for the LPG (liquefied petroleum gas) olefins as the
      nature (Bronsted-to-Lewis ratio) of the acid/active sites was not significantly
      altered upon steaming. Steam deactivation of ZSM-5 had also no significant effect
      on aromatics formation which was enhanced at higher conversion levels. Coke
      remained low with both fresh and steam-deactivated P/ZSM-5 additives.

PMID- 29065481
TI  - CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor
      Growth.
AB  - CD47 is a glycoprotein of the immunoglobulin superfamily that is often
      overexpressed in different types of hematological and solid cancer tumors and
      plays important role in blocking phagocytosis, increased tumor survival,
      metastasis and angiogenesis. In the present report, we designed CAR (chimeric
      antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain
      variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for
      targeting different cancer cell lines. CD47-CAR-T cells effectively killed
      ovarian, pancreatic and other cancer cells and produced high level of cytokines
      that correlated with expression of CD47 antigen. In addition, CD47-CAR-T cells
      significantly blocked BxPC3 pancreatic xenograft tumor growth after intratumoral
      injection into NSG mice. Moreover, we humanized mouse CD47 ScFv and showed that
      it effectively bound CD47 antigen. The humanized CD47-CAR-T cells also
      specifically killed ovarian, pancreatic, and cervical cancer cell lines and
      produced IL-2 that correlated with expression of CD47. Thus, CD47-CAR-T cells can
      be used as a novel cellular therapeutic agent for treating different types of
      cancer.

PMID- 29065482
TI  - Photo Protection of Haematococcus pluvialis Algae by Astaxanthin: Unique
      Properties of Astaxanthin Deduced by EPR, Optical and Electrochemical Studies.
AB  - Abstract The antioxidant astaxanthin is known to accumulate in Haematococcus
      pluvialis algae under unfavorable environmental conditions for normal cell
      growth. The accumulated astaxanthin functions as a protective agent against
      oxidative stress damage, and tolerance to excessive reactive oxygen species (ROS)
      is greater in astaxanthin-rich cells. The detailed mechanisms of protection have
      remained elusive, however, our Electron Paramagnetic Resonance (EPR), optical and
      electrochemical studies on carotenoids suggest that astaxanthin's efficiency as a
      protective agent could be related to its ability to form chelate complexes with
      metals and to be esterified, its inability to aggregate in the ester form, its
      high oxidation potential and the ability to form proton loss neutral radicals
      under high illumination in the presence of metal ions. The neutral radical
      species formed by deprotonation of the radical cations can be very effective
      quenchers of the excited states of chlorophyll under high irradiation.

PMID- 29065483
TI  - Rosemary Essential Oil-Loaded Lipid Nanoparticles: In Vivo Topical Activity from
      Gel Vehicles.
AB  - Although rosemary essential oil (EO) shows many biological activities, its
      topical benefits have not been clearly demonstrated. In this work, we assessed
      the effects on skin hydration and elasticity of rosemary EO after topical
      application via gel vehicles in human volunteers. To improve its topical
      efficacy, rosemary EO was loaded into lipid nanoparticles (NLCs) consisting of
      cetyl palmitate as a solid lipid, and non-ionic surfactants. Such NLCs were
      prepared using different ratios of EO/solid lipid and those containing EO 3% w/w
      and cetyl pamitate 7% w/w were selected for in vivo studies, showing the best
      technological properties (small particle size, low polydispersity index and good
      stability). Gels containing free EO or EO-loaded NLCs were applied on the hand
      skin surface of ten healthy volunteers twice a day for one week. Skin hydration
      and elasticity changes were recorded using the instrument Soft Plus. Gels
      containing EO-loaded NLCs showed a significant increase in skin hydration in
      comparison with gels containing free EO. Skin elasticity increased, as well,
      although to a lesser extent. The results of this study point out the usefulness
      of rosemary EO-loaded NLCs for the treatment of cutaneous alterations involving
      loss of skin hydration and elasticity.

PMID- 29065479
TI  - Psoriasis and Cardiovascular Comorbidities: Focusing on Severe Vascular Events,
      Cardiovascular Risk Factors and Implications for Treatment.
AB  - Psoriasis is a common and chronic inflammatory disease of the skin. It may impair
      the physical and psychosocial function of patients and lead to decreased quality
      of life. Traditionally, psoriasis has been regarded as a disease affecting only
      the skin and joints. More recently, studies have shown that psoriasis is a
      systemic inflammatory disorder which can be associated with various
      comorbidities. In particular, psoriasis is associated with an increased risk of
      developing severe vascular events such as myocardial infarction and stroke. In
      addition, the prevalence rates of cardiovascular risk factors are increased,
      including hypertension, diabetes mellitus, dyslipidemia, obesity, and metabolic
      syndrome. Consequently, mortality rates have been found to be increased and life
      expectancy decreased in patients with psoriasis, as compared to the general
      population. Various studies have also shown that systemic treatments for
      psoriasis, including methotrexate and tumor necrosis factor-alpha inhibitors, may
      significantly decrease cardiovascular risk. Mechanistically, the presence of
      common inflammatory pathways, secretion of adipokines, insulin resistance,
      angiogenesis, oxidative stress, microparticles, and hypercoagulability may
      explain the association between psoriasis and cardiometabolic disorders. In this
      article, we review the evidence regarding the association between psoriasis and
      cardiovascular comorbidities, focusing on severe vascular events, cardiovascular
      risk factors and implications for treatment.

PMID- 29065487
TI  - Enhancing Photovoltaic Performance Using Broadband Luminescent Down-Shifting by
      Combining Multiple Species of Eu-Doped Silicate Phosphors.
AB  - This paper demonstrates the application of a broadband luminescent downshifting
      (LDS) layer with multiple species of europium (Eu)-doped silicate phosphors using
      spin-on film technique to enhance the photovoltaic efficiency of crystalline
      silicon solar cells. The surface morphology of the deposited layer was examined
      using a scanning electron microscope (SEM). The chemical composition of the Eu
      doped silicate phosphors was analyzed using energy-dispersive X-ray spectroscopy
      (EDS). The fluorescence emission of the Eu-doped silicate phosphors was
      characterized using photoluminescence (PL) measurements at room temperature. We
      also compared the optical reflectance and external quantum efficiency (EQE)
      response of cells with combinations of various Eu-doped phosphors species. The
      cell coated with two species of Eu-doped phosphors achieved a conversion
      efficiency enhancement (?eta) of 19.39%, far exceeding the ?eta = 15.08% of the
      cell with one species of Eu-doped phosphors and the ?eta = 8.51% of the reference
      cell with the same silicate layer without Eu-doped phosphors.

PMID- 29065484
TI  - Mycosporine-Like Amino Acids: Potential Health and Beauty Ingredients.
AB  - Human skin is constantly exposed to damaging ultraviolet radiation (UVR), which
      induces a number of acute and chronic disorders. To reduce the risk of UV-induced
      skin injury, people apply an additional external protection in the form of
      cosmetic products containing sunscreens. Nowadays, because of the use of some
      chemical filters raises a lot of controversies, research focuses on exploring
      novel, fully safe and highly efficient natural UV-absorbing compounds that could
      be used as active ingredients in sun care products. A promising alternative is
      the application of multifunctional mycosporine-like amino acids (MAAs), which can
      effectively compete with commercially available filters. Here, we outline a
      complete characterization of these compounds and discuss their enormous
      biotechnological potential with special emphasis on their use as sunscreens,
      activators of cells proliferation, anti-cancer agents, anti-photoaging molecules,
      stimulators of skin renewal, and functional ingredients of UV-protective
      biomaterials.

PMID- 29065485
TI  - A Wearable Magneto-Inertial System for Gait Analysis (H-Gait): Validation on
      Normal Weight and Overweight/Obese Young Healthy Adults.
AB  - Background: Wearable magneto-inertial sensors are being increasingly used to
      obtain human motion measurements out of the lab, although their performance in
      applications requiring high accuracy, such as gait analysis, are still a subject
      of debate. The aim of this work was to validate a gait analysis system (H-Gait)
      based on magneto-inertial sensors, both in normal weight (NW) and
      overweight/obese (OW) subjects. The validation is performed against a reference
      multichannel recording system (STEP32), providing direct measurements of gait
      timings (through foot-switches) and joint angles in the sagittal plane (through
      electrogoniometers). Methods: Twenty-two young male subjects were recruited for
      the study (12 NW, 10 OW). After positioning body-fixed sensors of both systems,
      each subject was asked to walk, at a self-selected speed, over a 14-m straight
      path for 12 trials. Gait signals were recorded, at the same time, with the two
      systems. Spatio-temporal parameters, ankle, knee, and hip joint kinematics were
      extracted analyzing an average of 89 +/- 13 gait cycles from each lower limb.
      Intraclass correlation coefficient and Bland-Altmann plots were used to compare H
      Gait and STEP32 measurements. Changes in gait parameters and joint kinematics of
      OW with respect NW were also evaluated. Results: The two systems were highly
      consistent for cadence, while a lower agreement was found for the other spatio
      temporal parameters. Ankle and knee joint kinematics is overall comparable. Joint
      ROMs values were slightly lower for H-Gait with respect to STEP32 for the ankle
      (by 1.9 degrees  for NW, and 1.6 degrees  for OW) and for the knee (by 4.1
      degrees  for NW, and 1.8 degrees  for OW). More evident differences were found
      for hip joint, with ROMs values higher for H-Gait (by 6.8 degrees  for NW, and
      9.5 degrees  for OW). NW and OW showed significant differences considering STEP32
      (p = 0.0004), but not H-Gait (p = 0.06). In particular, overweight/obese subjects
      showed a higher cadence (55.0 vs. 52.3 strides/min) and a lower hip ROM (23.0
      degrees  vs. 27.3 degrees ) than normal weight subjects. Conclusions: The two
      systems can be considered interchangeable for what concerns joint kinematics,
      except for the hip, where discrepancies were evidenced. Differences between
      normal and overweight/obese subjects were statistically significant using STEP32.
      The same tendency was observed using H-Gait.

PMID- 29065486
TI  - Pleiotropic Role of Puupehenones in Biomedical Research.
AB  - Marine sponges represent a vast source of metabolites with very interesting
      potential biomedical applications. Puupehenones are sesquiterpene quinones
      isolated from sponges of the orders Verongida and Dictyoceratida. This family of
      chemical compounds is composed of a high number of metabolites, including
      puupehenone, the most characteristic compound of the family. Chemical synthesis
      of puupehenone has been reached by different routes, and the special chemical
      reactivity of this molecule has allowed the synthesis of many puupehenone-derived
      compounds. The biological activities of puupehenones are very diverse, including
      antiangiogenic, antitumoral, antioxidant, antimicrobial, immunomodulatory and
      antiatherosclerotic effects. Despite the very important roles described for
      puupehenones concerning different pathologies, the exact mechanism of action of
      these compounds and the putative therapeutic effects in vivo remain to be
      elucidated. This review offers an updated and global view about the biology of
      puupehenones and their therapeutic possibilities in human diseases such as
      cancer.

PMID- 29065488
TI  - Few-Flakes Reduced Graphene Oxide Sensors for Organic Vapors with a High Signal
      to-Noise Ratio.
AB  - This paper reports our findings on how to prepare a graphene oxide-based gas
      sensor for sensing fast pulses of volatile organic compounds with a better signal
      to-noise ratio. We use rapid acetone pulses of varying concentrations to test the
      sensors. First, we compare the effect of graphene oxide deposition method
      (dielectrophoresis versus solvent evaporation) on the sensor's response. We find
      that dielectrophoresis yields films with uniform coverage and better sensor
      response. Second, we examine the effect of chemical reduction. Contrary to prior
      reports, we find that graphene oxide reduction leads to a reduction in sensor
      response and current noise, thus keeping the signal-to-noise ratio the same. We
      found that if we sonicated the sensor in acetone, we created a sensor with a few
      flakes of reduced graphene oxide. Such sensors provided a higher signal-to-noise
      ratio that could be correlated to the vapor concentration of acetone with better
      repeatability. Modeling shows that the sensor's response is due to one-site
      Langmuir adsorption or an overall single exponent process. Further, the
      desorption of acetone as deduced from the sensor recovery signal follows a single
      exponent process. Thus, we show a simple way to improve the signal-to-noise ratio
      in reduced graphene oxide sensors.

PMID- 29065489
TI  - Advances in Single-Chain Nanoparticles for Catalysis Applications.
AB  - Enzymes are the most efficient catalysts known for working in an aqueous
      environment near room temperature. The folding of individual polymer chains to
      functional single-chain nanoparticles (SCNPs) offers many opportunities for the
      development of artificial enzyme-mimic catalysts showing both high catalytic
      activity and specificity. In this review, we highlight recent results obtained in
      the use of SCNPs as bioinspired, highly-efficient nanoreactors (3-30 nm) for the
      synthesis of a variety of nanomaterials (inorganic nanoparticles, quantum dots,
      carbon nanodots), polymers, and chemical compounds, as well as nanocontainers for
      CO2 capture and release.

PMID- 29065490
TI  - Immunotherapy for Pediatric Brain Tumors.
AB  - Malignant brain tumors are the most common cause of solid cancer death in
      children. New targeted therapies are vital to improve treatment outcomes, but
      must be developed to enable trafficking across the blood brain barrier (BBB).
      Since activated T cells cross the BBB, cancer immunotherapy can be harnessed to
      unlock the cytotoxic potential of the immune system. However, standard of care
      treatments (i.e., chemotherapy and radiation) applied concomitant to pediatric
      brain tumor immunotherapy may abrogate induction of immunotherapeutic responses.
      This review will discuss the development of immunotherapies within this paradigm
      using emerging approaches being investigated in phase I/II trials in children
      with refractory brain tumors, including checkpoint inhibitors, vaccine
      immunotherapy, and adoptive cell therapy.

PMID- 29065491
TI  - How Do Communities Use a Participatory Public Health Approach to Build
      Resilience? The Los Angeles County Community Disaster Resilience Project.
AB  - Community resilience is a key concept in the National Health Security Strategy
      that emphasizes development of multi-sector partnerships and equity through
      community engagement. Here, we describe the advancement of CR principles through
      community participatory methods in the Los Angeles County Community Disaster
      Resilience (LACCDR) initiative. LACCDR, an initiative led by the Los Angeles
      County Department of Public Health with academic partners, randomized 16
      community coalitions to implement either an Enhanced Standard Preparedness or
      Community Resilience approach over 24 months. Facilitated by a public health
      nurse or community educator, coalitions comprised government agencies, community
      focused organizations and community members. We used thematic analysis of data
      from focus groups (n = 5) and interviews (n = 6 coalition members; n = 16
      facilitators) to compare coalitions' strategies for operationalizing community
      resilience levers of change (engagement, partnership, self-sufficiency,
      education). We find that strategies that included bidirectional learning helped
      coalitions understand and adopt resilience principles. Strategies that
      operationalized community resilience levers in mutually reinforcing ways (e.g.,
      disseminating information while strengthening partnerships) also secured
      commitment to resilience principles. We review additional challenges and
      successes in achieving cross-sector collaboration and engaging at-risk groups in
      the resilience versus preparedness coalitions. The LACCDR example can inform
      strategies for uptake and implementation of community resilience and uptake of
      the resilience concept and methods.

PMID- 29065492
TI  - The Prevalence and Predictors of Dietary Supplement Use in the Australian
      Population.
AB  - Current dietary supplement use in Australia is not well described. We
      investigated the prevalence and predictors of supplement use in the Australian
      population (n = 19,257) using data from the 2014-2015 National Health Survey. We
      reported the prevalence of supplement use by sex and age group and investigated
      the independent predictors of supplement use in adults, adolescents, and children
      using multiple logistic regression models. A total of 43.2% of adults (34.9% of
      males, 50.3% of females), 20.1% of adolescents (19.7% of males, 20.6% of
      females), and 23.5% of children (24.4% of males, 22.5% of females) used at least
      one dietary supplement in the previous two weeks. The most commonly used
      supplements were multivitamins and/or multiminerals and fish oil preparations. In
      adults, independent predictors of supplement use included being female,
      increasing age, being born outside Australia and other main English-speaking
      countries, having a higher education level, having a healthy BMI compared to
      those who were obese, being physically active, and being a non-smoker. To our
      knowledge, this is the first detailed investigation of dietary supplement use in
      a nationally-representative sample of the Australian population. Future studies
      investigating the contribution of supplements to overall dietary intakes of
      vitamins, minerals, and omega-3 fatty acids are warranted.

PMID- 29065493
TI  - Trace Oxygen Sensitive Material Based on Two Porphyrin Derivatives in a
      Heterodimeric Complex.
AB  - The successful preparation of a novel dimer complex formed between 5,10,15,20
      tetrakis(3,4-dimethoxyphenyl)-porphyrin Fe(III) chloride and (5,10,15,20
      tetraphenylporphinato) dichlorophosphorus(V) chloride using the well-known
      reactivity of the P-X bond is reported. The obtained complex was characterized by
      UV-vis, Fourier transform infrared spectroscopy (FT-IR), fluorescence, 1H-NMR,
      13C-NMR, and 31P-NMR spectroscopic techniques and also by additional
      Heteronuclear Single Quantum Coherence (HSQC) and Heteronuclear Multiple Bond
      Correlation (HMBC) experiments in order to correctly assign the NMR signals.
      Scanning electron microscopy (SEM) and EDX quantifications completed the
      characterizations. This novel porphyrin dimer complex demonstrated fluorescence
      sensing of H2O2 in water for low oxygen concentrations in the range of 40-90 uM
      proving medical relevance for early diagnosis of diseases such as Alzheimer's,
      Parkinson's, Huntington's, and even cancer because higher concentrations of H2O2
      than 50 MUM are consideredcytotoxic for life. Due to its optical properties, this
      novel metalloporphyrin-porphyrin based complex is expected to show PDT and
      bactericidal activity under visible-light irradiation.

PMID- 29065494
TI  - Human Metapneumovirus Attachment Protein Contributes to Neutrophil Recruitment
      into the Airways of Infected Mice.
AB  - Human Metapneumovirus (HMPV) is a leading respiratory pathogen that causes lower
      respiratory tract infections worldwide. Acute HMPV infection induces an
      exacerbated inflammatory neutrophilic response leading to bronchiolitis and
      pneumonia. However, the mechanism by which the virus regulates neutrophil
      infiltration into the airways still remains unexplored. In this work, we used an
      experimental mouse model of HMPV infection to demonstrate that the attachment (G)
      protein of HMPV contributes to the recruitment of neutrophils into the airways
      and modulate the production of neutrophil chemoattractants and Type I IFN
      responses, specifically IFN-alpha. These findings provide the first evidence that
      the HMPV G protein contributes to the in vivo neutrophilic response to HMPV
      infection and furthers our understanding on virus induced inflammatory responses
      in the airways.

PMID- 29065495
TI  - Importance-Performance Analysis (IPA) of Foodservice Operation, Dietary Life
      Education, and Nutrition Counseling Tasks of Nutrition Teachers and Dietitians in
      Jeju, Korea.
AB  - The purpose of this study was to analyze foodservice operation, dietary life
      education, and nutrition counseling tasks of nutrition teachers and dietitians in
      elementary, middle, and high schools in Jeju, Korea, and to provide effective
      ways to implement dietary life education and nutrition counseling in schools.
      This study surveyed 94 nutrition teachers and 46 dietitians working at
      elementary, middle, and high schools in Jeju during 7-14 May 2015. The importance
      and performance of 16 tasks of nutrition teachers and dietitians were measured
      using questionnaires. The data was analyzed by using the SPSS software and
      Importance-Performance Analysis (IPA). Importance was ranked in the order of
      foodservice operation (4.72), dietary life education (4.37), and nutrition
      counseling (4.24); and performance was ranked in the order of foodservice
      operation (4.48), dietary life education (3.70), and nutrition counseling (3.22).
      The importance-performance matrix showed that in Quadrant 4, the "Concentrate
      Here" item was "nutrition and dietary life education for students", while in
      Quadrant 2, the "Possible Overkill" item was "cost control and office
      management". These findings suggest that it is important to reduce unnecessary
      administrative and office management tasks in order for nutrition teachers and
      dietitians to implement effective nutrition education, dietary life education,
      and nutrition counseling programs.

PMID- 29065496
TI  - Curcumin: A Review of Its' Effects on Human Health.
AB  - Turmeric, a spice that has long been recognized for its medicinal properties, has
      received interest from both the medical/scientific world and from culinary
      enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the
      management of oxidative and inflammatory conditions, metabolic syndrome,
      arthritis, anxiety, and hyperlipidemia. It may also help in the management of
      exercise-induced inflammation and muscle soreness, thus enhancing recovery and
      performance in active people. In addition, a relatively low dose of the complex
      can provide health benefits for people that do not have diagnosed health
      conditions. Most of these benefits can be attributed to its antioxidant and anti
      inflammatory effects. Ingesting curcumin by itself does not lead to the
      associated health benefits due to its poor bioavailability, which appears to be
      primarily due to poor absorption, rapid metabolism, and rapid elimination. There
      are several components that can increase bioavailability. For example, piperine
      is the major active component of black pepper and, when combined in a complex
      with curcumin, has been shown to increase bioavailability by 2000%. Curcumin
      combined with enhancing agents provides multiple health benefits. The purpose of
      this review is to provide a brief overview of the plethora of research regarding
      the health benefits of curcumin.

PMID- 29065497
TI  - Barriers and Facilitators to the Elimination of Asbestos Related Diseases
      Stakeholders' Perspectives.
AB  - Despite sound scientific knowledge and evidence that any exposure to asbestos
      fibers in all of its forms, are carcinogenic to humans, its presence, use and
      trade is still substantial, including in the World Health Organization (WHO)
      European Region. Banning the production and use of all forms of asbestos, as
      recommended by the International Labour Organization (ILO) and WHO, has been
      proven as the most efficient evidence-based strategy to eliminate Asbestos
      Related Diseases (ARDs). To effectively move elimination of ARDs forward,
      attaining a greater understanding of key stakeholders perspectives was identified
      as an important action. The WHO Regional Office for Europe, the European Centre
      for Environment and Health, undertook semi-structured interviews, and follow-up
      discussions with diverse representatives dealing professionally with asbestos.
      The interview questionnaire was developed based on the current ARDs WHO Report,
      the Evidence Implementation Model for Public Health and categories of the theory
      of diffusion. Data were attained on three main questions within the interview
      questionnaire: (1) Identifying barriers to implementation of WHO evidence-based
      asbestos recommendations; (2) Describing roles of key stakeholders; and, (3)
      Proposing possible solutions. The results demonstrated use of sound and
      convincing scientific evidence along with economic evidence and facilitators can
      be used to achieve evidence-based policy development, and comprehensive diverse
      actions.

PMID- 29065498
TI  - A High-Temperature MEMS Surface Fence for Wall-Shear-Stress Measurement in
      Scramjet Flow.
AB  - A new variant of MEMS surface fence is proposed for shear-stress estimation under
      high-speed, high-temperature flow conditions. Investigation of high-temperature
      resistance including heat-resistant mechanism and process, in conjunction with
      high-temperature packaging design, enable the sensor to be used in environment up
      to 400  degrees C. The packaged sensor is calibrated over a range of ~65 Pa and
      then used to examine the development of the transient flow of the scramjet
      ignition process (Mach 2 airflow, stagnation pressure, and a temperature of 0.8
      MPa and 950 K, respectively). The results show that the sensor is able to detect
      the transient flow conditions of the scramjet ignition process including shock
      impact, flow correction, steady state, and hydrogen off.

PMID- 29065499
TI  - An Overview of Dietary Interventions and Strategies to Optimize the Management of
      Non-Alcoholic Fatty Liver Disease.
AB  - Aim: To investigate the efficacy of lifestyle adjustment strategies as a
      preventive measure and/or treatment of obesity-related non-alcoholic fatty liver
      disease in adults. Method: A systematic review of literature through 1 July 2017
      on the PubMed Database was performed. A comprehensive search was conducted using
      key terms, such as non-alcoholic fatty liver disease (NAFLD), combined with
      lifestyle intervention, diet, and exercise. All of the articles and studies
      obtained from the search were reviewed. Redundant literature was excluded.
      Results: Several types of dietary compositions and exercise techniques were
      identified. Most studies concluded and recommended reduction in the intake of
      saturated and trans fatty acids, carbohydrates, and animal-based protein, and
      increased intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty
      acids (MUFAs), plant-based proteins, antioxidants, and other nutrients was
      recommended. The Mediterranean and Paleo diet both seem to be promising schemes
      for NAFLD patients to follow. Exercise was also encouraged, but the type of
      exercise did not affect its efficacy as a NAFLD treatment when the duration is
      consistent. Conclusions: Although these different dietary strategies and exercise
      regimens can be adopted to treat NAFLD, current literature on the topic is
      limited in scope. Further research should be conducted to truly elucidate which
      lifestyle adjustments individually, and in combination, may facilitate patients
      with obesity-related NAFLD.

PMID- 29065500
TI  - Monitoring Autophagy in the Model Green Microalga Chlamydomonas reinhardtii.
AB  - Autophagy is an intracellular catabolic system that delivers cytoplasmic
      constituents and organelles in the vacuole. This degradative process is mediated
      by a group of proteins coded by autophagy-related (ATG) genes that are widely
      conserved from yeasts to plants and mammals. Homologs of ATG genes have been also
      identified in algal genomes including the unicellular model green alga
      Chlamydomonas reinhardtii. The development of specific tools to monitor autophagy
      in Chlamydomonas has expanded our current knowledge about the regulation and
      function of this process in algae. Recent findings indicated that autophagy is
      regulated by redox signals and the TOR network in Chlamydomonas and revealed that
      this process may play in important role in the control of lipid metabolism and
      ribosomal protein turnover in this alga. Here, we will describe the different
      techniques and approaches that have been reported to study autophagy and
      autophagic flux in Chlamydomonas.

PMID- 29065501
TI  - Standard Assays for the Study of Autophagy in the Ex Vivo Retina.
AB  - Autophagy is a catabolic pathway that mediates the degradation and recycling of
      intracellular components, and is a key player in a variety of physiological
      processes in cells and tissues. Recent studies of autophagy in the eye suggest
      that this pathway is fundamental for the preservation of retinal homeostasis.
      Given its accessible location outside the brain, the retina is an ideal organ in
      which to study the central nervous system and a wide range of neuronal processes,
      from development to neurodegeneration. Here we review several methods used to
      assess autophagy in the retina in both physiological and pathological conditions.

PMID- 29065502
TI  - Recovery of Oil with Unsaturated Fatty Acids and Polyphenols from
      Chaenomelessinensis (Thouin) Koehne: Process Optimization of Pilot-Scale
      Subcritical Fluid Assisted Extraction.
AB  - The potential effects of three modern extraction technologies (cold-pressing,
      microwaves and subcritical fluids) on the recovery of oil from
      Chaenomelessinensis (Thouin) Koehne seeds have been evaluated and compared to
      those of conventional chemical extraction methods (Soxhlet extraction). This oil
      contains unsaturated fatty acids and polyphenols. Subcritical fluid extraction
      (SbFE) provided the highest yield-25.79 g oil/100 g dry seeds-of the three
      methods. Moreover, the fatty acid composition in the oil samples was analysed
      using gas chromatography-mass spectrometry. This analysis showed that the
      percentages of monounsaturated (46.61%), and polyunsaturated fatty acids
      (42.14%), after applying SbFE were higher than those obtained by Soxhlet, cold
      pressing or microwave-assisted extraction. In addition, the oil obtained under
      optimized SbFE conditions (35 min extraction at 35  degrees C with four
      extraction cycles), showed significant polyphenol (527.36 mg GAE/kg oil), and
      flavonoid (15.32 mg RE/kg oil), content, had a good appearance and was of high
      quality.

PMID- 29065503
TI  - Aptamers for DNA Damage and Repair.
AB  - DNA is damaged on a daily basis, which can lead to heritable mutations and the
      activation of proto-oncogenes. Therefore, DNA damage and repair are critical risk
      factors in cancer, aging and disease, and are the underlying bases of most
      frontline cancer therapies. Much of our current understanding of the mechanisms
      that maintain DNA integrity has been obtained using antibody-based assays. The
      oligonucleotide equivalents of antibodies, known as aptamers, have emerged as
      potential molecular recognition rivals. Aptamers possess several ideal properties
      including chemical stability, in vitro selection and lack of batch-to-batch
      variability. These properties have motivated the incorporation of aptamers into a
      wide variety of analytical, diagnostic, research and therapeutic applications.
      However, their use in DNA repair studies and DNA damage therapies is surprisingly
      un-tapped. This review presents an overview of the progress in selecting and
      applying aptamers for DNA damage and repair research.

PMID- 29065504
TI  - A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with
      NADPH Oxidases, Angiogenesis, and Apoptosis.
AB  - Oxidative stress refers to elevated reactive oxygen species (ROS) levels, and
      NADPH oxidases (NOXs), which are one of the most important sources of ROS.
      Oxidative stress plays important roles in the etiologies, pathological
      mechanisms, and treatment strategies of vascular diseases. Additionally,
      oxidative stress affects mechanisms of carcinogenesis, tumor growth, and
      prognosis in malignancies. Nearly all solid tumors show stimulation of neo
      vascularity, termed angiogenesis, which is closely associated with malignant
      aggressiveness. Thus, cancers can be seen as a type of vascular disease.
      Oxidative stress-induced functions are regulated by complex endogenous mechanisms
      and exogenous factors, such as medication and diet. Although understanding these
      regulatory mechanisms is important for improving the prognosis of urothelial
      cancer, it is not sufficient, because there are controversial and conflicting
      opinions. Therefore, we believe that this knowledge is essential to discuss
      observations and treatment strategies in urothelial cancer. In this review, we
      describe the relationships between members of the NOX family and tumorigenesis,
      tumor growth, and pathological mechanisms in urological cancers including
      prostate cancer, renal cell carcinoma, and urothelial cancer. In addition, we
      introduce natural compounds and chemical agents that are associated with ROS
      induced angiogenesis or apoptosis.

PMID- 29065505
TI  - Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity.
AB  - Compared to other types of cells, neurons express the largest number of diverse
      mRNAs, including neuron-specific ones. This mRNA diversity is required for
      neuronal function, memory storage, maintenance and retrieval. Regulation of
      translation in neurons is very complicated and involves various proteins. Some
      proteins, implementing translational control in other cell types, are used by
      neurons for synaptic plasticity. In this review, we discuss the neuron-specific
      activity of four kinases: protein kinase R (PKR), PKR-like endoplasmic reticulum
      kinase (PERK), general control nonderepressible 2 kinase (GCN2), and heme
      reguated eIF2alpha kinase (HRI), the substrate for which is alpha-subunit of
      eukaryotic initiation factor 2 (eIF2alpha). Phosphorylation of eIF2alpha is
      necessary for the cell during stress conditions, such as lack of amino acids,
      energy stress or viral infection. We propose that, during memory formation,
      neurons use some mechanisms similar to those involved in the cellular stress. The
      four eIF2alpha kinases regulate translation of certain mRNAs containing upstream
      open reading frames (uORFs). These mRNAs encode proteins involved in the
      processes of long-term potentiation (LTP) or long-term depression (LTD). The
      review examines some neuronal proteins for which translation regulation by eIF2
      was suggested and checked experimentally. Of such proteins, we pay close
      attention to protein kinase Mzeta, which is involved in memory storage and
      regulated at the translational level.

PMID- 29065506
TI  - Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor
      Identifies Molecular Pathways Implicated in Their Impaired Differentiation.
AB  - Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy
      (EDMD), a disorder causing progressive skeletal muscle wasting, irregular heart
      rhythms and contractures of major tendons. RNA sequencing was performed on
      differentiating wildtype and emerin-null myogenic progenitors to identify
      molecular pathways implicated in EDMD, 340 genes were uniquely differentially
      expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes
      were uniquely expressed in emerin-null cells; 1706 genes were shared among both
      wildtype and emerin-null cells. One thousand and forty-seven transcripts showed
      differential expression during the transition from day 1 to day 2. Four hundred
      and thirty-one transcripts showed altered expression in both wildtype and emerin
      null cells. Two hundred and ninety-five transcripts were differentially expressed
      only in emerin-null cells and 321 transcripts were differentially expressed only
      in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified
      pathways implicated in impaired emerin-null differentiation, including cell
      signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem
      cell differentiation, and multiple muscle development and myogenic
      differentiation pathways. Functional enrichment analysis showed biological
      functions associated with the growth of muscle tissue and myogenesis of skeletal
      muscle were inhibited. The large number of differentially expressed transcripts
      upon differentiation induction suggests emerin functions during transcriptional
      reprograming of progenitors to committed myoblasts.

PMID- 29065508
TI  - 'I Can Step outside My Comfort Zone.'
AB  - On embarking upon such a multifactorial, professional degree as Pharmacy,
      students often find it difficult to meld the scientific- and practice-based
      components of the course. In final year of the undergraduate Masters of Pharmacy
      degree (MPharm) within the School of Pharmacy and Life Sciences at Robert Gordon
      University (RGU), students undertake a research project within a specific area.
      The aims of this study were to explore the effectiveness of a novel practice
      based approach to a biomedical science project, to identify elements of
      difficulty in the process, and to explore students' perceptions and reflections.
      Final year students were assigned to perform a systematic literature review
      working within a defined area of pharmacovigilance. Students were given
      individual ownership of the research question and were able to choose a topic of
      interest. Following the successful completion of the assignment, students were
      invited to explore their attitudes and views of the project and reflect on the
      process through a focus group using a talking wall method. The findings clearly
      identified a shift in mindset from predominantly negative opinions initially to
      an overwhelming positive viewpoint.

PMID- 29065509
TI  - An Improved Method of Pose Estimation for Lighthouse Base Station Extension.
AB  - In 2015, HTC and Valve launched a virtual reality headset empowered with
      Lighthouse, the cutting-edge space positioning technology. Although Lighthouse is
      superior in terms of accuracy, latency and refresh rate, its algorithms do not
      support base station expansion, and is flawed concerning occlusion in moving
      targets, that is, it is unable to calculate their poses with a small set of
      sensors, resulting in the loss of optical tracking data. In view of these
      problems, this paper proposes an improved pose estimation algorithm for cases
      where occlusion is involved. Our algorithm calculates the pose of a given object
      with a unified dataset comprising of inputs from sensors recognized by all base
      stations, as long as three or more sensors detect a signal in total, no matter
      from which base station. To verify our algorithm, HTC official base stations and
      autonomous developed receivers are used for prototyping. The experiment result
      shows that our pose calculation algorithm can achieve precise positioning when a
      few sensors detect the signal.

PMID- 29065510
TI  - An Investigation of the Antioxidant Capacity in Extracts from Moringa oleifera
      Plants Grown in Jamaica.
AB  - Moringa oleifera trees grow well in Jamaica and their parts are popularly used
      locally for various purposes and ailments. Antioxidant activities in Moringa
      oleifera samples from different parts of the world have different ranges. This
      study was initiated to determine the antioxidant activity of Moringa oleifera
      grown in Jamaica. Dried and milled Moringa oleifera leaves were extracted with
      ethanol/water (4:1) followed by a series of liquid-liquid extractions. The
      antioxidant capacities of all fractions were tested using a 2,2-diphenyl-1
      picrylhydrazyl (DPPH) assay. IC50 values (the amount of antioxidant needed to
      reduce 50% of DPPH) were then determined and values for the extracts ranged from
      177 to 4458 MUg/mL. Extracts prepared using polar solvents had significantly
      higher antioxidant capacities than others and may have clinical applications in
      any disease characterized by a chronic state of oxidative stress, such as sickle
      cell anemia. Further work will involve the assessment of these extracts in a
      sickle cell model of oxidative stress.

PMID- 29065507
TI  - Fatty Acids Consumption: The Role Metabolic Aspects Involved in Obesity and Its
      Associated Disorders.
AB  - Obesity and its associated disorders, such as insulin resistance, dyslipidemia,
      metabolic inflammation, dysbiosis, and non-alcoholic hepatic steatosis, are
      involved in several molecular and inflammatory mechanisms that alter the
      metabolism. Food habit changes, such as the quality of fatty acids in the diet,
      are proposed to treat and prevent these disorders. Some studies demonstrated that
      saturated fatty acids (SFA) are considered detrimental for treating these
      disorders. A high fat diet rich in palmitic acid, a SFA, is associated with lower
      insulin sensitivity and it may also increase atherosclerosis parameters. On the
      other hand, a high intake of eicosapentaenoic (EPA) and docosahexaenoic (DHA)
      fatty acids may promote positive effects, especially on triglyceride levels and
      increased high-density lipoprotein (HDL) levels. Moreover, polyunsaturated fatty
      acids (PUFAs) and monounsaturated fatty acids (MUFAs) are effective at limiting
      the hepatic steatosis process through a series of biochemical events, such as
      reducing the markers of non-alcoholic hepatic steatosis, increasing the gene
      expression of lipid metabolism, decreasing lipogenic activity, and releasing
      adiponectin. This current review shows that the consumption of unsaturated fatty
      acids, MUFA, and PUFA, and especially EPA and DHA, which can be applied as food
      supplements, may promote effects on glucose and lipid metabolism, as well as on
      metabolic inflammation, gut microbiota, and hepatic metabolism.

PMID- 29065511
TI  - Novel Tetra-Primer ARMS-PCR Assays for Thiopurine Intolerance Susceptibility
      Mutations NUDT15 c.415C>T and TPMT c.719A>G (TPMT*3C) in East Asians.
AB  - Thiopurines are clinically useful in the management of diverse immunological and
      malignant conditions. Nevertheless, these purine analogues can cause lethal
      myelosuppression, which may be prevented by prospective testing for variants in
      the thiopurine S-methyltransferase (TPMT) and, in East Asians, Nudix hydrolase 15
      (NUDT15) genes. Two single-tube, tetra-primer amplification refractory mutation
      system polymerase chain reaction (ARMS-PCR) assays were developed to genotype the
      common loss-of-function variants NUDT15 c.415C>T (rs116855232) and TPMT*3C
      c.719A>G (rs1142345). In a group of 60 unselected patients, one and seven were
      found to be homozygous and heterozygous, respectively, for NUDT15 c.415C>T; one
      was found to be heterozygous for TPMT*3C c.719A>G. There was no non-specific
      amplification, and the genotypes were 100% concordant with Sanger sequencing.
      Limit-of-detection for both assays was below 1 ng of heterozygous template per
      reaction. Time- and cost-effective ARMS-PCR assays, suitable for genotyping East
      Asian patients for thiopurine intolerance, were successfully developed and
      validated.

PMID- 29065512
TI  - Anti-Inflammatory Dembranoids from the Soft Coral Lobophytum crassum.
AB  - Abstract: Cembrane-type diterpenoids are among the most frequently encountered
      natural products from the soft corals of the genus Lobophytum. In the course of
      our investigation to identify anti-inflammatory constituents from a wild-type
      soft coral Lobophytumcrassum, two new cembranoids, lobophyolide A (1) and B (2),
      along with five known compounds (3-7), were isolated. The structures of these
      natural products were identified using NMR and MS spectroscopic analyses.
      Compound 1 was found to possess the first identified alpha-epoxylactone group
      among all cembrane-type diterpenoids. The in vitro anti-inflammatory effect of
      compounds 1-5 was evaluated. The results showed that compounds 1-5 not only
      reduced IL-12 release, but also attenuated NO production in LPS-activated
      dendritic cells. Our data indicated that the isolated series of cembrane-type
      diterpenoids demonstrated interesting structural features and anti-inflammatory
      activity which could be further developed into therapeutic entities.

PMID- 29065515
TI  - Laser-Interferometric Broadband Seismometer for Epicenter Location Estimation.
AB  - In this paper, we suggest a seismic signal measurement system that uses a laser
      interferometer. The heterodyne laser interferometer is used as a seismometer due
      to its high accuracy and robustness. Seismic data measured by the laser
      interferometer is used to analyze crucial earthquake characteristics. To measure
      P-S time more precisely, the short time Fourier transform and instantaneous
      frequency estimation methods are applied to the intensity signal ( I y ) of the
      laser interferometer. To estimate the epicenter location, the range difference of
      arrival algorithm is applied with the P-S time result. The linear matrix equation
      of the epicenter localization can be derived using P-S time data obtained from
      more than three observatories. We prove the performance of the proposed algorithm
      through simulation and experimental results.

PMID- 29065513
TI  - Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and
      Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N.
AB  - Argan oil is widely used in Morocco in traditional medicine. Its ability to treat
      cardiovascular diseases is well-established. However, nothing is known about its
      effects on neurodegenerative diseases, which are often associated with increased
      oxidative stress leading to lipid peroxidation and the formation of 7
      ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces
      oxidative stress, inflammation and cell death, it is important to identify
      compounds able to impair its harmful effects. These compounds may be either
      natural or synthetic molecules or mixtures of molecules such as oils. In this
      context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir
      (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were
      determined by different chromatographic techniques; and (ii) their anti-oxidant
      and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25
      50 uM; 24 h) without and with argan oil (0.1% v/v) or alpha-tocopherol (400 uM,
      positive control) were evaluated with complementary techniques of cellular and
      molecular biology. Among the unsaturated fatty acids present in argan oils,
      oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest
      quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0).
      Several phytosterols were found, mainly schottenol and spinasterol (specific to
      argan oil), cycloartenol, beta-amyrin and citrostadienol. alpha- and gamma
      tocopherols were also present. Tyrosol and protocatechic acid were the only
      polyphenols detected. Argan and extra virgin olive oils have many compounds in
      common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres
      (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and
      extra virgin olive oils have anti-oxidant properties. Argan oils were able to
      attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell
      growth inhibition, increased plasma membrane permeability, mitochondrial,
      peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy
      (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N
      oligodendrocytes provide evidence that argan oil is able to counteract the toxic
      effects of 7KC on nerve cells, thus suggesting that some of its compounds could
      prevent or mitigate neurodegenerative diseases to the extent that they are able
      to cross the blood-brain barrier.

PMID- 29065516
TI  - Effect of MgO Underlying Layer on the Growth of GaOx Tunnel Barrier in Epitaxial
      Fe/GaOx/(MgO)/Fe Magnetic Tunnel Junction Structure.
AB  - We investigated the effect of a thin MgO underlying layer (~3 monoatomic layers)
      on the growth of GaOx tunnel barrier in Fe/GaOx/(MgO)/Fe(001) magnetic tunnel
      junctions. To obtain a single-crystalline barrier, an in situ annealing was
      conducted with the temperature being raised up to 500  degrees C under an O2
      atmosphere. This annealing was performed after the deposition of the GaOx on the
      Fe(001) bottom electrode with or without the MgO(001) underlying layer.
      Reflection high-energy electron diffraction patterns after the annealing
      indicated the formation of a single-crystalline layer regardless of with or
      without the MgO layer. Ex situ structural studies such as transmission electron
      microscopy revealed that the GaOx grown on the MgO underlying layer has a cubic
      MgAl2O4-type spinel structure with a (001) orientation. When without MgO layer,
      however, a Ga-Fe-O ternary compound having the same crystal structure and
      orientation as the crystalline GaOx was observed. The results indicate that the
      MgO underlying layer effectively prevents the Fe bottom electrode from oxidation
      during the annealing process. Tunneling magneto-resistance effect was observed
      only for the sample with the MgO underlying layer, suggesting that Ga-Fe-O layer
      is not an effective tunnel-barrier.

PMID- 29065514
TI  - The Role of MDM2 in Promoting Genome Stability versus Instability.
AB  - In cancer, the mouse double minute 2 (MDM2) is an oncoprotein that contributes to
      the promotion of cell growth, survival, invasion, and therapeutic resistance. The
      impact of MDM2 on cell survival versus cell death is complex and dependent on
      levels of MDM2 isoforms, p53 status, and cellular context. Extensive
      investigations have demonstrated that MDM2 protein-protein interactions with p53
      and other p53 family members (p63 and p73) block their ability to function as
      transcription factors that regulate cell growth and survival. Upon genotoxic
      insults, a dynamic and intricately regulated DNA damage response circuitry is
      activated leading to release of p53 from MDM2 and activation of cell cycle
      arrest. What ensues following DNA damage, depends on the extent of DNA damage and
      if the cell has sufficient DNA repair capacity. The well-known auto-regulatory
      loop between p53-MDM2 provides an additional layer of control as the cell either
      repairs DNA damage and survives (i.e., MDM2 re-engages with p53), or undergoes
      cell death (i.e., MDM2 does not re-engage p53). Furthermore, the decision to live
      or die is also influenced by chromatin-localized MDM2 which directly interacts
      with the Mre11-Rad50-Nbs1 complex and inhibits DNA damage-sensing giving rise to
      the potential for increased genome instability and cellular transformation.

PMID- 29065517
TI  - Correction: Gustafson et al., Whole Genome Sequencing Revealed Mutations in Two
      Independent Genes as the Underlying Cause of Retinal Degeneration in an Ashkenazi
      Jewish Pedigree. Genes 2017, 8, 210.
AB  - Following publication of our article [1], we identified discrepancies between the
      pedigree shown in Figure 1 and the rest of the text.[...].

PMID- 29065518
TI  - Low-Cost Interrogation Technique for Dynamic Measurements with FBG-Based Devices.
AB  - Fiber Bragg gratings are widely used optical fiber sensors for measuring
      temperature and/or mechanical strain. Nevertheless, the high cost of the
      interrogation systems is the most important drawback for their large commercial
      application. In this work, an in-line Fabry-Perot interferometer based edge
      filter is explored in the interrogation of fiber Bragg grating dynamic
      measurements up to 5 kHz. Two devices an accelerometer and an arterial pulse wave
      probe were interrogated with the developed approach and the results were compared
      with a commercial interrogation monitor. The data obtained with the edge filter
      are in agreement with the commercial device, with a maximum RMSE of 0.05 being
      able to meet the requirements of the measurements. Resolutions of 3.6 pm and 2.4
      pm were obtained, using the optical accelerometer and the arterial pulse wave
      probe, respectively.

PMID- 29065519
TI  - Evaluation of the Effects of Nanoparticle Mixtures on Brassica Seed Germination
      and Bacterial Bioluminescence Activity Based on the Theory of Probability.
AB  - Effects of binary mixtures of six metal oxide nanoparticles (NPs; 54
      combinations) on the activities of seed germination and bacterial bioluminescence
      were investigated using the theory of probability. The observed toxicities of
      various NPs combinations were compared with the theoretically expected
      toxicities, calculated based on individual NPs toxicities. Different
      sensitivities were observed depending on the concentrations and the types of NPs.
      The synergistic mode (67%; observed toxicity greater than expected toxicity) was
      predominantly observed in the bioluminescence test, whereas both synergistic
      (47%) and additive (50%) modes were prevalent in the activity of seed
      germination. With regard to overall analysis, a slightly high percentage (56%) of
      the synergistic mode of action was (30 out of 54 binary mixture combinations; p <
      0.0392) observed. These results suggest that the exposure of an NPs mixture in
      the environment may lead to a similar or higher toxicity level than the sum of
      its constituent NPs would suggest. In addition, one organism for assessment did
      not always show same results as those from a different assessment. Therefore,
      combining results of different organisms exposed to a wide range of
      concentrations of binary mixture will more properly predict and evaluate the
      expected ecotoxicity of pollutants on environments.

PMID- 29065520
TI  - Analysis of Floral Volatile Components and Antioxidant Activity of Different
      Varieties of Chrysanthemum morifolium.
AB  - This study investigated the volatile flavor compounds and antioxidant properties
      of the essential oil of chrysanthemums that was extracted from the fresh flowers
      of 10 taxa of Chrysanthemum morifolium from three species; namely Dendranthema
      morifolium (Ramat.) Yellow, Dendranthema morifolium (Ramat.) Red, Dendranthema
      morifolium (Ramat.) Pink, Dendranthema morifolium (Ramat.) White, Pericallis
      hybrid Blue, Pericallis hybrid Pink, Pericallis hybrid Purple, Bellis perennis
      Pink, Bellis perennis Yellow, and Bellis perennis White. The antioxidant capacity
      of the essential oil was assayed by spectrophotometric analysis. The volatile
      flavor compounds from the fresh flowers were collected using dynamic headspace
      collection, analyzed using auto thermal desorber-gas chromatography/mass
      spectrometry, and identified with quantification using the external standard
      method. The antioxidant activities of Chrysanthemum morifolium were evaluated by
      DPPH and FRAP assays, and the results showed that the antioxidant activity of
      each sample was not the same. The different varieties of fresh Chrysanthemum
      morifolium flowers were distinguished and classified by fingerprint similarity
      evaluation, principle component analysis (PCA), and cluster analysis. The results
      showed that the floral volatile component profiles were significantly different
      among the different Chrysanthemum morifolium varieties. A total of 36 volatile
      flavor compounds were identified with eight functional groups: hydrocarbons,
      terpenoids, aromatic compounds, alcohols, ketones, ethers, aldehydes, and esters.
      Moreover, the variability among Chrysanthemum morifolium in basis to the data,
      and the first three principal components (PC1, PC2, and PC3) accounted for
      96.509% of the total variance (55.802%, 30.599%, and 10.108%, respectively). PCA
      indicated that there were marked differences among Chrysanthemum morifolium
      varieties. The cluster analysis confirmed the results of the PCA analysis. In
      conclusion, the results of this study provide a basis for breeding Chrysanthemum
      cultivars with desirable floral scents, and they further support the view that
      some plants are promising sources of natural antioxidants.

PMID- 29065521
TI  - A New Polar Transfer Alignment Algorithm with the Aid of a Star Sensor and Based
      on an Adaptive Unscented Kalman Filter.
AB  - Because of the harsh polar environment, the master strapdown inertial navigation
      system (SINS) has low accuracy and the system model information becomes abnormal.
      In this case, existing polar transfer alignment (TA) algorithms which use the
      measurement information provided by master SINS would lose their effectiveness.
      In this paper, a new polar TA algorithm with the aid of a star sensor and based
      on an adaptive unscented Kalman filter (AUKF) is proposed to deal with the
      problems. Since the measurement information provided by master SINS is
      inaccurate, the accurate information provided by the star sensor is chosen as the
      measurement. With the compensation of lever-arm effect and the model of star
      sensor, the nonlinear navigation equations are derived. Combined with the
      attitude matching method, the filter models for polar TA are designed. An AUKF is
      introduced to solve the abnormal information of system model. Then, the AUKF is
      used to estimate the states of TA. Results have demonstrated that the performance
      of the new polar TA algorithm is better than the state-of-the-art polar TA
      algorithms. Therefore, the new polar TA algorithm proposed in this paper is
      effectively to ensure and improve the accuracy of TA in the harsh polar
      environment.

PMID- 29065522
TI  - Ti-Based Biomedical Material Modified with TiOx/TiNx Duplex Bioactivity Film via
      Micro-Arc Oxidation and Nitrogen Ion Implantation.
AB  - Titanium (Ti) and Ti-based alloy are widely used in the biomedical field owing to
      their excellent mechanical compatibility and biocompatibility. However, the
      bioinert bioactivity and biotribological properties of titanium limit its
      clinical application in implants. In order to improve the biocompatibility of
      titanium, we modified its surface with TiOx/TiNx duplex composite films using a
      new method via micro-arc oxidation (MAO) and nitrogen ion implantation (NII)
      treatment. The structural characterization results revealed that the modified
      film was constructed by nanoarrays composed of TiOx/TiNx composite nanostitches
      with a size of 20~40 nm. Meanwhile, comparing this with pure Ti, the friction
      property, wear resistance, and bioactivity were significantly improved based on
      biotribological results and in vitro bioactivity tests.

PMID- 29065523
TI  - The Transcriptomes of Xiphinema index and Longidorus elongatus Suggest
      Independent Acquisition of Some Plant Parasitism Genes by Horizontal Gene
      Transfer in Early-Branching Nematodes.
AB  - Nematodes have evolved the ability to parasitize plants on at least four
      independent occasions, with plant parasites present in Clades 1, 2, 10 and 12 of
      the phylum. In the case of Clades 10 and 12, horizontal gene transfer of plant
      cell wall degrading enzymes from bacteria and fungi has been implicated in the
      evolution of plant parasitism. We have used ribonucleic acid sequencing (RNAseq)
      to generate reference transcriptomes for two economically important nematode
      species, Xiphinema index and Longidorus elongatus, representative of two genera
      within the early-branching Clade 2 of the phylum Nematoda. We used a
      transcriptome-wide analysis to identify putative horizontal gene transfer events.
      This represents the first in-depth transcriptome analysis from any plant
      parasitic nematode of this clade. For each species, we assembled ~30 million
      Illumina reads into a reference transcriptome. We identified 62 and 104
      transcripts, from X. index and L. elongatus, respectively, that were putatively
      acquired via horizontal gene transfer. By cross-referencing horizontal gene
      transfer prediction with a phylum-wide analysis of Pfam domains, we identified
      Clade 2-specific events. Of these, a GH12 cellulase from X. index was analysed
      phylogenetically and biochemically, revealing a likely bacterial origin and
      canonical enzymatic function. Horizontal gene transfer was previously shown to be
      a phenomenon that has contributed to the evolution of plant parasitism among
      nematodes. Our findings underline the importance and the extensiveness of this
      phenomenon in the evolution of plant-parasitic life styles in this speciose and
      widespread animal phylum.

PMID- 29065525
TI  - The SAR Payload Design and Performance for the GF-3 Mission.
AB  - This paper describes the C-band multi-polarization Synthetic Aperture Radar (SAR)
      sensor for the Gaofen-3 (GF-3) mission. Based on the requirement analysis, the
      design of working modes and SAR payload are given. An accurate antenna model is
      introduced for the pattern optimization and SAR performance calculation. The
      paper concludes with an overview of predicted performance which was verified by
      in-orbit tests.

PMID- 29065524
TI  - Parents' Perceived Barriers to Accessing Sports and Recreation Facilities in
      Ontario, Canada: Exploring the Relationships between Income, Neighbourhood
      Deprivation, and Community.
AB  - Sports and recreation facilities provide places where children can be physically
      active. Previous research has shown that availability is often worse in lower
      socioeconomic status (SES) areas, yet others have found inverse relationships, no
      relationships, or mixed findings. Since children's health behaviours are
      influenced by their parents, it is important to understand parents' perceived
      barriers to accessing sports and recreation facilities. Data from computer
      assisted telephone interviews with parents living in Ontario, Canada were merged
      via postal codes with neighbourhood deprivation data. Multivariable logistic
      regression modeling was used to estimate the likelihood that parents reported
      barriers to accessing local sports and recreation facilities. Parents with lower
      household incomes were more likely to report barriers to access. For each unit
      increase in deprivation score (i.e., more deprived), the likelihood of reporting
      a barrier increased 16% (95% CI: 1.04, 1.28). For parents, the relationships
      between household income, neighbourhood-level deprivation, and barriers are
      complex. Understanding these relationships is important for research, policy and
      planning, as parental barriers to opportunities for physical activity have
      implications for child health behaviours, and ultimately childhood overweight and
      obesity.

PMID- 29065526
TI  - Bias-Voltage Stabilizer for HVHF Amplifiers in VHF Pulse-Echo Measurement
      Systems.
AB  - The impact of high-voltage-high-frequency (HVHF) amplifiers on echo-signal
      quality is greater with very-high-frequency (VHF, >=100 MHz) ultrasound
      transducers than with low-frequency (LF, <=15 MHz) ultrasound transducers. Hence,
      the bias voltage of an HVHF amplifier must be stabilized to ensure stable echo
      signal amplitudes. We propose a bias-voltage stabilizer circuit to maintain
      stable DC voltages over a wide input range, thus reducing the harmonic-distortion
      components of the echo signals in VHF pulse-echo measurement systems. To confirm
      the feasibility of the bias-voltage stabilizer, we measured and compared the
      deviations in the gain of the HVHF amplifier with and without a bias-voltage
      stabilizer. Between -13 and 26 dBm, the measured gain deviations of a HVHF
      amplifier with a bias-voltage stabilizer are less than that of an amplifier
      without a bias-voltage stabilizer. In order to confirm the feasibility of the
      bias-voltage stabilizer, we compared the pulse-echo responses of the amplifiers,
      which are typically used for the evaluation of transducers or electronic
      components used in pulse-echo measurement systems. From the responses, we
      observed that the amplitudes of the echo signals of a VHF transducer triggered by
      the HVHF amplifier with a bias-voltage stabilizer were higher than those of the
      transducer triggered by the HVHF amplifier alone. The second, third, and fourth
      harmonic-distortion components of the HVHF amplifier with the bias-voltage
      stabilizer were also lower than those of the HVHF amplifier alone. Hence, the
      proposed scheme is a promising method for stabilizing the bias voltage of an HVHF
      amplifier, and improving the echo-signal quality of VHF transducers.

PMID- 29065527
TI  - Factors Influencing Early Feeding of Foods and Drinks Containing Free Sugars-A
      Birth Cohort Study.
AB  - Early feeding of free sugars to young children can increase the preference for
      sweetness and the risk of consuming a cariogenic diet high in free sugars later
      in life. This study aimed to investigate early life factors influencing early
      introduction of foods/drinks containing free sugars. Data from an ongoing
      population-based birth cohort study in Australia were used. Mothers of newborn
      children completed questionnaires at birth and subsequently at ages 3, 6, 12, and
      24 months. The outcome was reported feeding (Yes/No) at age 6-9 months of common
      foods/drinks sources of free sugars (hereafter referred as foods/drinks with free
      sugars). Household income quartiles, mother's sugar-sweetened beverage (SSB)
      consumption, and other maternal factors were exposure variables. Analysis was
      conducted progressively from bivariate to multivariable log-binomial regression
      with robust standard error estimation to calculate prevalence ratios (PR) of
      being fed foods/drinks with free sugars at an early age (by 6-9 months). Models
      for both complete cases and with multiple imputations (MI) for missing data were
      generated. Of 1479 mother/child dyads, 21% of children had been fed foods/drinks
      with free sugars. There was a strong income gradient and a significant positive
      association with maternal SSB consumption. In the complete-case model, income Q1
      and Q2 had PRs of 1.9 (1.2-3.1) and 1.8 (1.2-2.6) against Q4, respectively. The
      PR for mothers ingesting SSB everyday was 1.6 (1.2-2.3). The PR for children who
      had been breastfed to at least three months was 0.6 (0.5-0.8). Similar findings
      were observed in the MI model. Household income at birth and maternal behaviours
      were significant determinants of early feeding of foods/drinks with free sugars.

PMID- 29065529
TI  - Immobilization of Lead Migrating from Contaminated Soil in Rhizosphere Soil of
      Barley (Hordeum vulgare L.) and Hairy Vetch (Vicia villosa) Using Hydroxyapatite.
AB  - This study conducted plant growth tests using a rhizobox system to quantitatively
      determine the distance of immobilization lead migrating from contaminated soil
      into uncontaminated rhizosphere soil, and to assess the lead phases accumulated
      in rhizosphere soil by sequential extraction. Without the hydroxyapatite,
      exchangeable lead fractions increased as the rhizosphere soil got closer to the
      contaminated soil. Exchangeable lead fractions were higher even in the
      rhizosphere soil that shares a boundary with the root surface than in the soil
      before being planted. Thus, plant growth of hairy vetch was lower in the soil
      without the hydroxyapatite than in the soil with the hydroxyapatite. The presence
      of hydroxyapatite may immobilize the majority of lead migrating from contaminated
      soil into the rhizosphere soil within 1 mm from the contaminated soil. The
      dominant lead fraction in the rhizosphere soil with the hydroxyapatite was
      residual. Thus, plant growth was not suppressed and the lead concentration of the
      plant shoot remained at the background level. These results indicate that the
      presence of hydroxyapatite in the rhizosphere soil at 5% wt may immobilize most
      of the lead migrating into the rhizosphere soil within 1 mm from the contaminated
      soil, resulting in the prevention of lead migration toward the root surface.

PMID- 29065528
TI  - Understanding the Relationship between Socio-Economic Status, Physical Activity
      and Sedentary Behaviour, and Adiposity in Young Adult South African Women Using
      Structural Equation Modelling.
AB  - Socio-economic status (SES) is an important predictor of obesity, but how it is
      associated with differences in physical activity and sedentary behaviour is less
      clear. This cross-sectional study examined the association between SES (sum of
      household assets), physical activity and sedentary time, and how they predict
      adiposity. Socio-demographic, anthropometric, and physical activity data on rural
      (n = 509) and urban (n = 510) South African women (18-23 years) were collected.
      Overweight and obesity prevalence, and sedentary time, were higher; and moderate
      vigorous intensity physical activity (MVPA) was lower, in the urban sample.
      Structural equation models (SEMs) were constructed for BMI and waist
      circumference. In the urban sample SES had a direct inverse effect on MVPA (beta;
      95% CI, -41.69; -73.40 to -9.98), while in the rural sample SES had a direct
      effect on BMI (beta; 95% CI, 0.306; 0.03 to 0.59). In the pooled sample, SES had
      a direct inverse effect on MVPA (beta; 95% CI, -144; -170.34 to -119.04), and
      MVPA was directly associated with BMI (beta; 95% CI, 0.04; 0.01 to 0.08). The
      influence of SES, and the role of physical activity and sedentary time on
      adiposity differs between the urban and rural samples, and the importance of
      other environmental and behavioural factors must be considered in the development
      of obesity and the design of effective interventions.

PMID- 29065532
TI  - A Constitutive Relationship for Gravelly Soil Considering Fine Particle
      Suffusion.
AB  - Suffusion erosion may occur in sandy gravel dam foundations that use suspended
      cutoff walls. This erosion causes a loss of fine particles, degrades the soil
      strength and deformation moduli, and adversely impacts the cutoff walls of the
      dam foundation, as well as the overlying dam body. A comprehensive evaluation of
      these effects requires models that quantitatively describe the effects of fine
      particle losses on the stress-strain relationships of sandy gravels. In this
      work, we propose an experimental scheme for studying these types of models, and
      then perform triaxial and confined compression tests to determine the effects of
      particle losses on the stress-strain relationships. Considering the Duncan-Chang
      E-B model, quantitative expressions describing the relationship between the
      parameters of the model and the particle losses were derived. The results show
      that particle losses did not alter the qualitative stress-strain characteristics
      of the soils; however, the soil strength and deformation moduli were degraded. By
      establishing the relationship between the parameters of the model and the losses,
      the same model can then be used to describe the relationship between sandy
      gravels and erosion levels that vary in both time and space.

PMID- 29065530
TI  - Analysis of Intracellular Metabolites from Microorganisms: Quenching and
      Extraction Protocols.
AB  - Sample preparation is one of the most important steps in metabolome analysis. The
      challenges of determining microbial metabolome have been well discussed within
      the research community and many improvements have already been achieved in last
      decade. The analysis of intracellular metabolites is particularly challenging.
      Environmental perturbations may considerably affect microbial metabolism, which
      results in intracellular metabolites being rapidly degraded or metabolized by
      enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism
      is a pre-requisite for accurate intracellular metabolite analysis. After
      quenching, metabolites need to be extracted from the intracellular compartment.
      The choice of the most suitable metabolite extraction method/s is another crucial
      step. The literature indicates that specific classes of metabolites are better
      extracted by different extraction protocols. In this review, we discuss the
      technical aspects and advancements of quenching and extraction of intracellular
      metabolite analysis from microbial cells.

PMID- 29065534
TI  - Development of a Telemetric, Miniaturized Electrochemical Amperometric Analyzer.
AB  - In this research, we developed a portable, three-electrode electrochemical
      amperometric analyzer that can transmit data to a PC or a tablet via Bluetooth
      communication. We performed experiments using an indium tin oxide (ITO) glass
      electrode to confirm the performance and reliability of the analyzer. The
      proposed analyzer uses a current-to-voltage (I/V) converter to convert the
      current generated by the reduction-oxidation (redox) reaction of the buffer
      solution to a voltage signal. This signal is then digitized by the processor. The
      configuration of the power and ground of the printed circuit board (PCB) layer is
      divided into digital and analog parts to minimize the noise interference of each
      part. The proposed analyzer occupies an area of 5.9 * 3.25 cm2 with a current
      resolution of 0.4 nA. A potential of 0~2.1 V can be applied between the working
      and the counter electrodes. The results of this study showed the accuracy of the
      proposed analyzer by measuring the Ruthenium(III) chloride ( Ru III )
      concentration in 10 mM phosphate-buffered saline (PBS) solution with a pH of 7.4.
      The measured data can be transmitted to a PC or a mobile such as a smartphone or
      a tablet PC using the included Bluetooth module. The proposed analyzer uses a 3.7
      V, 120 mAh lithium polymer battery and can be operated for 60 min when fully
      charged, including data processing and wireless communication.

PMID- 29065533
TI  - Leucine-Enriched Essential Amino Acids Augment Muscle Glycogen Content in Rats
      Seven Days after Eccentric Contraction.
AB  - Eccentric contractions induce muscle damage, which impairs recovery of glycogen
      and adenosine tri-phosphate (ATP) content over several days. Leucine-enriched
      essential amino acids (LEAAs) enhance the recovery in muscles that are damaged
      after eccentric contractions. However, the role of LEAAs in this process remains
      unclear. We evaluated the content in glycogen and high energy phosphates
      molecules (phosphocreatine (PCr), adenosine di-phosphate (ADP) and ATP) in rats
      that were following electrically stimulated eccentric contractions. Muscle
      glycogen content decreased immediately after the contraction and remained low for
      the first three days after the stimulation, but increased seven days after the
      eccentric contraction. LEAAs administration did not change muscle glycogen
      content during the first three days after the contraction. Interestingly,
      however, it induced a further increase in muscle glycogen seven days after the
      stimulation. Contrarily, ATP content decreased immediately after the eccentric
      contraction, and remained lower for up to seven days after. Additionally, LEAAs
      administration did not affect the ATP content over the experimental period.
      Finally, ADP and PCr levels did not significantly change after the contractions
      or LEAA administration. LEAAs modulate the recovery of glycogen content in muscle
      after damage-inducing exercise.

PMID- 29065531
TI  - Cyclodipeptides: An Overview of Their Biosynthesis and Biological Activity.
AB  - Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic
      peptides that are produced as secondary functional metabolites or side products
      of protein metabolism by bacteria, fungi, and animals. They are widespread in
      nature, and exhibit a broad variety of biological and pharmacological activities.
      CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the
      biosynthesis of the CDP core structure, which is further modified by tailoring
      enzymes often associated with CDP biosynthetic gene clusters. In this review, we
      provide a comprehensive summary of CDP biosynthetic pathways and modifying
      enzymes. We also discuss the biological properties of some known CDPs and their
      possible applications in metabolic engineering.

PMID- 29065535
TI  - A Hyperspectral Image Classification Framework with Spatial Pixel Pair Features.
AB  - During recent years, convolutional neural network (CNN)-based methods have been
      widely applied to hyperspectral image (HSI) classification by mostly mining the
      spectral variabilities. However, the spatial consistency in HSI is rarely
      discussed except as an extra convolutional channel. Very recently, the
      development of pixel pair features (PPF) for HSI classification offers a new way
      of incorporating spatial information. In this paper, we first propose an improved
      PPF-style feature, the spatial pixel pair feature (SPPF), that better exploits
      both the spatial/contextual information and spectral information. On top of the
      new SPPF, we further propose a flexible multi-stream CNN-based classification
      framework that is compatible with multiple in-stream sub-network designs. The
      proposed SPPF is different from the original PPF in its paring pixel selection
      strategy: only pixels immediately adjacent to the central one are eligible,
      therefore imposing stronger spatial regularization. Additionally, with off-the
      shelf classification sub-network designs, the proposed multi-stream, late-fusion
      CNN-based framework outperforms competing ones without requiring extensive
      network configuration tuning. Experimental results on three publicly available
      datasets demonstrate the performance of the proposed SPPF-based HSI
      classification framework.

PMID- 29065537
TI  - Fabrication of Composite Filaments with High Dielectric Permittivity for Fused
      Deposition 3D Printing.
AB  - Additive manufacturing of complex structures with spatially varying
      electromagnetic properties can enable new applications in high-technology sectors
      such as communications and sensors. This work presents the fabrication method as
      well as microstructural and dielectric characterization of bespoke composite
      filaments for fused deposition modeling (FDM) 3D printing of microwave devices
      with a high relative dielectric permittivity epsilon = 11 in the GHz frequency
      range. The filament is composed of 32 vol % of ferroelectric barium titanate
      (BaTiO 3 ) micro-particles in a polymeric acrylonitrile butadiene styrene (ABS)
      matrix. An ionic organic ester surfactant was added during formulation to enhance
      the compatibility between the polymer and the BaTiO 3 . To promote reproducible
      and robust printability of the fabricated filament, and to promote plasticity,
      dibutyl phthalate was additionally used. The combined effect of 1 wt % surfactant
      and 5 wt % plasticizer resulted in a uniform, many hundreds of meters, continuous
      filament of commercial quality capable of many hours of uninterrupted 3D
      printing. We demonstrate the feasibility of using the high dielectric constant
      filament for 3D printing through the fabrication of a range of optical devices.
      The approach herein may be used as a guide for the successful fabrication of many
      types of composite filament with varying functions for a broad range of
      applications.

PMID- 29065536
TI  - Comparison of the Micellar Incorporation and the Intestinal Cell Uptake of
      Cholecalciferol, 25-Hydroxycholecalciferol and 1-alpha-Hydroxycholecalciferol.
AB  - In the context of the global prevalence of vitamin D insufficiency, we compared
      two key determinants of the bioavailability of 3 vitamin D forms with significant
      biopotencies: cholecalciferol, 25-hydroxycholecalciferol and 1-alpha
      hydroxycholecalciferol. To this aim, we studied their incorporation into
      synthetic mixed micelles and their uptake by intestinal cells in culture. Our
      results show that 1-alpha-hydroxycholecalciferol was significantly more
      solubilized into mixed micelles compared to the other forms (1.6-fold and 2.9
      fold improvement compared to cholecalciferol and 25-hydroxycholecalciferol,
      respectively). In Caco-2 TC7 cells, the hydroxylated forms were taken up more
      efficiently than cholecalciferol (p < 0.05), and conversely to cholecalciferol,
      their uptake was neither SR-BI(Scavenger-Receptor class B type I)- nor NPC1L1
      (NPC1 like intracellular cholesterol transporter 1)-dependent. Besides, the
      apical membrane sodium-bile acid transporter ASBT (Apical Sodium-dependent Bile
      acid Transporter) was not involved, at least in vitro, in the uptake of any of
      the three vitamin D forms. Further investigations are needed to identify the
      uptake pathways of both 1-alpha-hydroxycholecalciferol and 25
      hydroxycholecalciferol. However, considering its high bioavailability, our
      results suggest the potential interest of using 1-alpha-hydroxycholecalciferol in
      the treatment of severe vitamin D deficiency.

PMID- 29065538
TI  - Stable and Fast-Response Capacitive Humidity Sensors Based on a ZnO
      Nanopowder/PVP-RGO Multilayer.
AB  - In this paper, capacitive-type humidity sensors were prepared by sequentially
      drop-coating the aqueous suspensions of zinc oxide (ZnO) nanopowders and
      polyvinyl pyrrolidone-reduced graphene oxide (PVP-RGO) nanocomposites onto
      interdigitated electrodes. Significant improvements in both sensitivity and
      linearity were achieved for the ZnO/PVP-RGO sensors compared with the PVP
      RGO/ZnO, PVP-RGO, and ZnO counterparts. Moreover, the produced ZnO/PVP-RGO
      sensors exhibited rather small hysteresis, fast response-recovery time, and long
      term stability. Based on morphological and structural analyses, it can be
      inferred that the excellent humidity sensing properties of the ZnO/PVP-RGO
      sensors may be attributed to the high surface-to-volume ratio of the multilayer
      structure and the supporting roles of the PVP-RGO nanocomposites. The results in
      this work hence provide adequate guidelines for designing high-performance
      humidity sensors that make use of the multilayer structure of semiconductor oxide
      materials and PVP-RGO nanocomposites.

PMID- 29065539
TI  - Ureidopyrazine Derivatives: Synthesis and Biological Evaluation as Anti
      Infectives and Abiotic Elicitors.
AB  - Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) has become a
      frequently deadly infection due to increasing antimicrobial resistance. This
      serious issue has driven efforts worldwide to discover new drugs effective
      against Mtb. One research area is the synthesis and evaluation of pyrazinamide
      derivatives as potential anti-TB drugs. In this paper we report the synthesis and
      biological evaluations of a series of ureidopyrazines. Compounds were synthesized
      by reacting alkyl/aryl isocyanates with aminopyrazine or with propyl 5
      aminopyrazine-2-carboxylate. Reactions were performed in pressurized vials using
      a CEM Discover microwave reactor with a focused field. Purity and chemical
      structures of products were assessed, and the final compounds were tested in
      vitro for their antimycobacterial, antibacterial, and antifungal activities.
      Propyl 5-(3-phenylureido)pyrazine-2-carboxylate (compound 4, MICMtb = 1.56
      MUg/mL, 5.19 MUM) and propyl 5-(3-(4-methoxyphenyl)ureido)pyrazine-2-carboxylate
      (compound 6, MICMtb = 6.25 MUg/mL, 18.91 MUM) had high antimycobacterial activity
      against Mtb H37Rv with no in vitro cytotoxicity on HepG2 cell line. Therefore 4
      and 6 are suitable for further structural modifications that might improve their
      biological activity and physicochemical properties. Based on the structural
      similarity to 1-(2-chloropyridin-4-yl)-3-phenylurea, a known plant growth
      regulator, two selected compounds were evaluated for similar activity as abiotic
      elicitors.

PMID- 29065540
TI  - Activation of Alkaline Irrigation Fluids in Endodontics.
AB  - In conventional endodontic treatment, alkaline solutions of sodium hypochlorite
      (NaOCl) and ethylenediaminetetraacetic acid (EDTA) are used in combination to
      disinfect the root canal system and to eliminate debris and smear layers. An
      important concept that has emerged over recent years is the use of active
      physical methods for agitating these fluids to improve their penetration within
      areas that are not reached by endodontic instruments and to accelerate the
      chemical actions of these alkaline fluids against planktonic microorganisms,
      biofilms, soft tissue remnants and smear layers. Ultrasonic agitation and more
      recently pulsed lasers have emerged as two promising methods for activating
      endodontic irrigation fluids. Ultrasonic agitation with piezoelectric devices
      employs a moving tip, while laser agitation uses a stationary tip. Both methods
      cause cavitation, followed by implosions and shear forces which assist with
      debridement. Fluid streaming further enhances the activity of the fluids. While
      agitation enhances performance of irrigants, extrusion of fluids from the root
      canal during activation is a hazard that must be controlled.

PMID- 29065542
TI  - Aspects of Solvent Chemistry for Calcium Hydroxide Medicaments.
AB  - Calcium hydroxide pastes have been used in endodontics since 1947. Most current
      calcium hydroxide endodontic pastes use water as the vehicle, which limits the
      dissolution of calcium hydroxide that can be achieved and, thereby, the maximum
      pH that can be achieved within the root canal system. Using polyethylene glycol
      as a solvent, rather than water, can achieve an increase in hydroxyl ions release
      compared to water or saline. By adopting non-aqueous solvents such as the
      polyethylene glycols (PEG), greater dissolution and faster hydroxyl ion release
      can be achieved, leading to enhanced antimicrobial actions, and other
      improvements in performance and biocompatibility.

PMID- 29065541
TI  - Screening and Biosensor-Based Approaches for Lung Cancer Detection.
AB  - Early diagnosis of lung cancer helps to reduce the cancer death rate
      significantly. Over the years, investigators worldwide have extensively
      investigated many screening modalities for lung cancer detection, including
      computerized tomography, chest X-ray, positron emission tomography, sputum
      cytology, magnetic resonance imaging and biopsy. However, these techniques are
      not suitable for patients with other pathologies. Developing a rapid and
      sensitive technique for early diagnosis of lung cancer is urgently needed.
      Biosensor-based techniques have been recently recommended as a rapid and cost
      effective tool for early diagnosis of lung tumor markers. This paper reviews the
      recent development in screening and biosensor-based techniques for early lung
      cancer detection.

PMID- 29065543
TI  - The Regulatory Mechanism of MLT/MT1 Signaling on the Growth of Antler Mesenchymal
      Cells.
AB  - Melatonin (MLT) plays an important role in regulating the physiological cycle of
      seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in
      the cambium layer of deer antler. However, the function and metabolic mechanism
      of MLT/MT1 signaling in the mesenchymal cells of sika deer remain to be further
      elucidated. In this work, we detected the effects of MLT/MT1 signaling on
      mesenchymal cells proliferation and the interaction between MLT/MT1 and IGF1/IGF1
      R signaling. The results show that (1) deer antler mesenchymal cells actually
      express MT1; (2) exogenous melatonin significantly promotes mesenchymal cells
      proliferation, while MT1 knock-down significantly impairs the positive effects of
      melatonin; and (3) melatonin significantly enhanced IGF1/IGF1-R signaling, as
      both the expression of IGF1 and IGF-1R increased, while MT1 knock-down
      significantly decreased IGF1-R expression and IGF1 synthesis. In summary, these
      data verified that MLT/MT1 signaling plays a crucial role in antler mesenchymal
      proliferation, which may be mediated by IGF1/IGF1-R.

PMID- 29065544
TI  - Pharmacological Effects of Two Novel Bombesin-Like Peptides from the Skin
      Secretions of Chinese Piebald Odorous Frog (Odorrana schmackeri) and European
      Edible Frog (Pelophylax kl. esculentus) on Smooth Muscle.
AB  - Bombesin-like peptides, which were identified from a diversity of amphibian skin
      secretions, have been demonstrated to possess several biological functions such
      as stimulation of smooth muscle contraction and regulation of food intake. Here,
      we report two novel bombesin-like peptides, bombesin-OS and bombesin-PE, which
      were isolated from Odorrana schmackeri and Pelophylax kl. esculentus,
      respectively. The mature peptides were identified and structurally confirmed by
      high performance Scliquid chromatography (HPLC) and tandem mass spectrometry
      (MS/MS). Subsequently, the effects of these purified chemically-synthetic
      peptides on smooth muscle were determined in bladder, uterus, and ileum. The
      synthetic replications were revealed to have significant pharmacological effects
      on these tissues. The EC50 values of bombesin-OS for bladder, uterus and ileum,
      were 10.8 nM, 33.64 nM, and 12.29 nM, respectively. Furthermore, compared with
      bombesin-OS, bombesin-PE showed similar contractile activity on ileum smooth
      muscle and uterus smooth muscle, but had a higher potency on bladder smooth
      muscle. The EC50 value of bombesin-OS for bladder was around 1000-fold less than
      that of bombesin-PE. This suggests that bombesin-OS and bombesin-PE have unique
      binding properties to their receptors. The precursor of bombesin-OS was
      homologous with that of a bombesin-like peptide, odorranain-BLP-5, and bombesin
      PE belongs to the ranatensin subfamily. We identified the structure of bombesin
      OS and bombesin-PE, two homologues peptides whose actions may provide a further
      clue in the classification of ranid frogs, also in the provision of new drugs for
      human health.

PMID- 29065545
TI  - Effectiveness of a Video-Versus Text-Based Computer-Tailored Intervention for
      Obesity Prevention after One Year: A Randomized Controlled Trial.
AB  - Computer-tailored programs may help to prevent overweight and obesity, which are
      worldwide public health problems. This study investigated (1) the 12-month
      effectiveness of a video- and text-based computer-tailored intervention on energy
      intake, physical activity, and body mass index (BMI), and (2) the role of
      educational level in intervention effects. A randomized controlled trial in The
      Netherlands was conducted, in which adults were allocated to a video-based
      condition, text-based condition, or control condition, with baseline, 6 months,
      and 12 months follow-up. Outcome variables were self-reported BMI, physical
      activity, and energy intake. Mixed-effects modelling was used to investigate
      intervention effects and potential interaction effects. Compared to the control
      group, the video intervention group was effective regarding energy intake after 6
      months (least squares means (LSM) difference = -205.40, p = 0.00) and 12 months
      (LSM difference = -128.14, p = 0.03). Only video intervention resulted in lower
      average daily energy intake after one year (d = 0.12). Educational role and BMI
      did not seem to interact with this effect. No intervention effects on BMI and
      physical activity were found. The video computer-tailored intervention was
      effective on energy intake after one year. This effect was not dependent on
      educational levels or BMI categories, suggesting that video tailoring can be
      effective for a broad range of risk groups and may be preferred over text
      tailoring.

PMID- 29065546
TI  - Nucleophilicities of Lewis Bases B and Electrophilicities of Lewis Acids A
      Determined from the Dissociation Energies of Complexes B?A Involving Hydrogen
      Bonds, Tetrel Bonds, Pnictogen Bonds, Chalcogen Bonds and Halogen Bonds.
AB  - It is shown that the dissociation energy D e for the process B?A = B + A for 250
      complexes B?A composed of 11 Lewis bases B (N2, CO, HC=CH, CH2=CH2, C3H6, PH3,
      H2S, HCN, H2O, H2CO and NH3) and 23 Lewis acids (HF, HCl, HBr, HC=CH, HCN, H2O,
      F2, Cl2, Br2, ClF, BrCl, H3SiF, H3GeF, F2CO, CO2, N2O, NO2F, PH2F, AsH2F, SO2,
      SeO2, SF2, and SeF2) can be represented to good approximation by means of the
      equation D e = c ' N B E A , in which N B is a numerical nucleophilicity assigned
      to B, E A is a numerical electrophilicity assigned to A, and c ' is a constant,
      conveniently chosen to have the value 1.00 kJ mol-1 here. The 250 complexes were
      chosen to cover a wide range of non-covalent interaction types, namely: (1) the
      hydrogen bond; (2) the halogen bond; (3) the tetrel bond; (4) the pnictogen bond;
      and (5) the chalcogen bond. Since there is no evidence that one group of non
      covalent interaction was fitted any better than the others, it appears the
      equation is equally valid for all the interactions considered and that the values
      of N B and E A so determined define properties of the individual molecules. The
      values of N B and E A can be used to predict the dissociation energies of a wide
      range of binary complexes B?A with reasonable accuracy.

PMID- 29065547
TI  - Phenolic Compounds Present Schinus terebinthifolius Raddi Influence the Lowering
      of Blood Pressure in Rats.
AB  - This study identified two phenolic compounds in Schinus terebinthifolius Raddi
      fruits: naringenin (first report in this species) and gallic acid. Their
      structures were elucidated by nuclear magnetic resonance (NMR) data (1H-, 13C
      NMR) and a high-performance liquid chromatography (HPLC) technique. A high
      content of phenolics (659.21 mg of gallic acid equivalents/g of sample-Folin
      Ciocalteau method) and total flavonoids (140.69 mg of rutin equivalents/g of
      sample-aluminum chloride method) were quantified in S. terebinthifolius, as well
      as high antioxidant activity (77.47%-2,2-diphenyl-1-picrylhydrazyl, DPPH method).
      The antihypertensive activity related to its phenolic content was investigated.
      After intravenous infusion in Wistar rats, these phenolics significantly reduced
      (p < 0.05) the systolic, median, and diastolic arterial pressures of individuals.
      The rotarod test was performed to determine the mechanism of action of the sample
      vasorelaxant effect. It was found that its action exceeded that of the positive
      control used (diazepam). This confirmed the vasodilatory activity exerted by S.
      terebinthifolius fruits is related to the phenolic compounds present in the
      plant, which are potent antioxidants and inhibit oxidative stress, mainly in the
      central nervous system.

PMID- 29065548
TI  - Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in
      Melatonin Induction in Plants.
AB  - Cadmium is a well-known elicitor of melatonin synthesis in plants, including
      rice. However, the mechanisms by which cadmium induces melatonin induction remain
      elusive. To investigate whether cadmium influences physical integrities in
      subcellular organelles, we treated tobacco leaves with either CdCl2 or AlCl3 and
      monitored the structures of subcellular organelles-such as chloroplasts,
      mitochondria, and the endoplasmic reticulum (ER)-using confocal microscopic
      analysis. Unlike AlCl3 treatment, CdCl2 (0.5 mM) treatment significantly
      disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of
      chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT)
      to encounter serotonin in the cytoplasm, leading to the synthesis of N
      acetylserotonin followed by melatonin synthesis. In fact, the disruption of
      chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of
      melatonin in rice leaves, which suggests that cadmium-treated chloroplast
      disruption plays an important role in inducing melatonin in plants by removing
      physical barriers, such as chloroplast double membranes, allowing SNAT to gain
      access to the serotonin substrate enriched in the cytoplasm.

PMID- 29065549
TI  - Generally Recognized as Safe: Uncertainty Surrounding E-Cigarette Flavoring
      Safety.
AB  - Despite scientific uncertainty regarding the relative safety of inhaling e
      cigarette aerosol and flavorings, some consumers regard the U.S. Food and Drug
      Administration's "generally recognized as safe" (GRAS) designation as evidence of
      flavoring safety. In this study, we assessed how college students' perceptions of
      e-cigarette flavoring safety are related to understanding of the GRAS
      designation. During spring 2017, an online questionnaire was administered to
      college students. Chi-square p-values and multivariable logistic regression were
      employed to compare perceptions among participants considering e-cigarette
      flavorings as safe and those considering e-cigarette flavorings to be unsafe. The
      total sample size was 567 participants. Only 22% knew that GRAS designation meant
      that a product is safe to ingest, not inhale, inject, or use topically. Of
      participants who considered flavorings to be GRAS, the majority recognized that
      the designation meant a product is safe to ingest but also considered it safe to
      inhale. Although scientific uncertainty on the overall safety of flavorings in e
      cigarettes remains, health messaging can educate the public about the GRAS
      designation and its irrelevance to e-cigarette safety.

PMID- 29065552
TI  - Synthesis and Properties of MQ Copolymers: Current State of Knowledge.
AB  - In this review, we discuss currently available studies on the synthesis and
      properties of MQ copolymers. The data on methods of producing hydrolytic and
      heterofunctional polycondensation of functional organosilanes as well as the
      obtaining MQ copolymers based on silicic acids and nature silicates are
      considered. The ratio of M and Q monomers and the production method determine the
      structure of MQ copolymers and, accordingly, their physicochemical
      characteristics. It is shown that the most successful synthetic approach is a
      polycondensation of organoalkoxysilanes in the medium of anhydrous acetic acid,
      which reduces the differences in reactivity of M and Q monomers and leads to
      obtaining a product with uniform composition in all fractions, with full absence
      of residual alkoxy-groups. The current concept of MQ copolymers is that of organo
      inorganic hybrid systems with nanosized crosslinked inorganic regions limited by
      triorganosilyl groups and containing residual hydroxyl groups. The systems can be
      considered as a peculiar molecular composites consisting of separate parts that
      play the role of a polymer matrix, a plasticizer, and a nanosized filler.

PMID- 29065553
TI  - Effects of Aqueous Extract of Three Cultivars of Banana (Musa acuminata) Fruit
      Peel on Kidney and Liver Function Indices in Wistar Rats.
AB  - Background:Musa acuminata fruit peels are used in the northern part of Nigeria
      for the treatment of hypertension and other cardiovascular related diseases. The
      effects of aqueous extracts of ripped fruit peel of three cultivars of Musa
      acuminata (Saro, Ominni and Oranta) on the hepatic and renal parameters of normal
      rats were examined. Methods: Fruit peel aqueous extracts (FPAE) of the 3
      cultivars of Bananas (100 mg/kg b.w.) were administered by oral intubation (that
      is through esophageal cannula) to normal rats (140-180 g) for a period of 28
      days. Blood samples were collected for determination of plasma aspartate amino
      transferase (AST), alanine amino transferase (ALT), alkaline phosphatase ALK-P),
      total protein, albumin, creatinine as well as urea. Results: From the results
      obtained, there were no significant (p < 0.05) changes in the ALK-P, AST, ALT,
      total protein and albumin among the experimental rats administered FPAE of the 3
      cultivars of Musa acuminata when compared with the normal control group. There
      was a significant (p < 0.05) increase in the level of serum creatinine (in mg/dL)
      (1.53 +/- 0.23) when compared to the normal control (0.72 +/- 0.15), Ominni (0.92
      +/- 0.39) and Oranta (0.74 +/- 0.22). Similarly, there was a significant (p <
      0.05) increase in the level of serum urea (in mg/dL) of Saro (41.56 +/- 4.68)
      when compared to the normal control (26.05 +/- 0.73), Ommini (28.44 +/- 2.43) and
      Oranta (26.10 +/- 2.94). Conclusion: The findings reveal the Saro cultivar of
      Musa acuminata to be nephrotoxic and not a good potential drug candidate among
      the cultivars studied hence should be discouraged in the treatment of
      hypertension and other cardiovascular related diseases.

PMID- 29065551
TI  - Molecular Docking and Screening Studies of New Natural Sortase A Inhibitors.
AB  - To date, multi-drug resistant bacteria represent an increasing health threat,
      with a high impact on mortality, morbidity, and health costs on a global scale.
      The ability of bacteria to rapidly and permanently acquire new virulence factors
      and drug-resistance elements requires the development of new antimicrobial agents
      and selection of new proper targets, such as sortase A. This specific bacterial
      target plays an important role in the virulence of many Gram-positive pathogens,
      and its inhibition should produce a mild evolutionary pressure which will not
      favor the development of resistance. A primary screening using a fluorescence
      resonance energy transfer assay was used to experimentally evaluate the
      inhibitory activity of several compounds on sortase A. Using molecular docking
      and structure-activity relationship analyses, several lead inhibitors were
      identified, which were further tested for antimicrobial activity using the well
      diffusion test and minimum inhibitory concentration. The toxicity was assessed
      using the Daphnia magna test and used as a future screening filter. Three natural
      compounds were identified in this study as promising candidates for further
      development into therapeutically useful anti-infective agents that could be used
      to treat infections caused by multi-drug resistant bacterial pathogens which
      include sortase A in their enzymatic set.

PMID- 29065554
TI  - New Triterpenoid Saponins from the Herb Hylomecon japonica.
AB  - Background: Hylomecon japonica, a plant of the Papaveraceae family which is well
      known for the alkaloids they produce, is a perennial plant widely distributed in
      the northeast, central and east regions of China. Although a variety of chemical
      constituents, including alkaloids, flavonoids, and megastigmoids, have been
      isolated from H. japonica, the investigation of saponins in H. japonica has not
      been reported until now. Methods: Various separation techniques, including
      polyporous resin column chromatography, silica gel column chromatography and hemi
      preparative HPLC were applied to the isolation of triterpenoid saponins, and
      chemical methods such as acid hydrolysis and spectroscopic methods including
      HRESIMS and NMR were applied to their structure elucidation, and the XTT
      reduction method was used to assay cytotoxicity. Results: Two new triterpenoid
      saponins, named hylomeconoside A (1) and B (2) which were identified as 3-O-beta
      d-galactopyranosyl-(1->2)-beta-d-glucuronopyranosyl-gypsogenin-28-O-beta-d
      xylopyranosyl-(1->3)-beta-d-xylopyranosyl-(1->4)-alpha-l-rhamnopyranosyl-(1->2)
      beta-d-quinovopyranoside (1) and 3-O-beta-d-galactopyranosyl-(1->2)-beta-d
      glucuronopyranosyl-gypsogenin-28-O-beta-d-xylopyranosyl-(1->3)-beta-d
      xylopyranosyl-(1->4)-alpha-l-rhamnopyranosyl-(1->2)-alpha-l-arabinopyranoside
      (2), and two known triterpenoid saponins identified as dubioside C (3) and
      lucyoside P (4) on the basis of spectroscopic and chemical evidence, were
      isolated from H. japonica. Compound 1 exhibited moderate cytotoxicity on MGC-803
      and HL-60 cells, with IC50 values of 43.8 and 32.4 MUg.mL-1, respectively.
      Conclusions: Compounds 1 and 2 are new saponins, and 1 is considered to be one of
      the antitumor principles in this plant. This is the first time that triterpenoid
      saponins have been isolated from plants of the Papaveraceae family.

PMID- 29065555
TI  - Reassessing the Chromosome Number and Morphology of the Turtle Ant Cephalotes
      pusillus (Klug, 1824) Using Karyomorphometrical Analysis and Observations of New
      Nesting Behavior.
AB  - Here we use karyomorphometrical analysis to characterize and evaluate the
      karyotype of the turtle ant Cephalotes pusillus (Klug, 1824). This is the first
      representative of this diverse ant genus to be cytogenetically studied. They bear
      a diploid chromosome set of 44 chromosomes, which, according to the centromeric
      index, are metacentric, submetacentric, and subtelocentric. This small ant is
      quite widely distributed in the Neotropics and seems to be well adapted to living
      in disturbed areas. Here we report the species nesting on dead trunks used to
      build fences at countryside houses and farms. On these nests, we observed some
      never reported behavior of C. pusillus: the ants appear to be able to dig by
      actively removing small fragments of dead wood fiber, hence expanding their nest
      cavities. It was not thought that Cephalotes species had this ability, given that
      they nest in preexisting cavities. Our observations are initial remarks that the
      small plier-like mandibles of C. pusillus may not be a constraint for this
      species, adding to our knowledge on ant nesting biology.

PMID- 29065556
TI  - Optical Methods in Fingerprint Imaging for Medical and Personality Applications.
AB  - Over the years, analysis and induction of personality traits has been a topic for
      individual subjective conjecture or speculation, rather than a focus of inductive
      scientific analysis. This study proposes a novel framework for analysis and
      induction of personality traits. First, 14 personality constructs based on the
      "Big Five" personality factors were developed. Next, a new fingerprint image
      algorithm was used for classification, and the fingerprints were classified into
      eight types. The relationship between personality traits and fingerprint type was
      derived from the results of the questionnaire survey. After comparison of pre
      test and post-test results, this study determined the induction ability of
      personality traits from fingerprint type. Experimental results showed that the
      left/right thumbprint type of a majority of subjects was left loop/right loop and
      that the personalities of individuals with this fingerprint type were moderate
      with no significant differences in the 14 personality constructs.

PMID- 29065550
TI  - Metallothioneins: Emerging Modulators in Immunity and Infection.
AB  - Metallothioneins (MTs) are a family of metal-binding proteins virtually expressed
      in all organisms including prokaryotes, lower eukaryotes, invertebrates and
      mammals. These proteins regulate homeostasis of zinc (Zn) and copper (Cu),
      mitigate heavy metal poisoning, and alleviate superoxide stress. In recent years,
      MTs have emerged as an important, yet largely underappreciated, component of the
      immune system. Innate and adaptive immune cells regulate MTs in response to
      stress stimuli, cytokine signals and microbial challenge. Modulation of MTs in
      these cells in turn regulates metal ion release, transport and distribution,
      cellular redox status, enzyme function and cell signaling. While it is well
      established that the host strictly regulates availability of metal ions during
      microbial pathogenesis, we are only recently beginning to unravel the interplay
      between metal-regulatory pathways and immunological defenses. In this
      perspective, investigation of mechanisms that leverage the potential of MTs to
      orchestrate inflammatory responses and antimicrobial defenses has gained
      momentum. The purpose of this review, therefore, is to illumine the role of MTs
      in immune regulation. We discuss the mechanisms of MT induction and signaling in
      immune cells and explore the therapeutic potential of the MT-Zn axis in
      bolstering immune defenses against pathogens.

PMID- 29065557
TI  - Protective Effects of Red Ginseng Oil against Abeta25-35-Induced Neuronal
      Apoptosis and Inflammation in PC12 Cells.
AB  - One of pathological characteristics of Alzheimer's disease (AD), aggregation and
      deposition of beta amyloid (Abeta), has been accepted as a potent activator of
      neuronal cell death. Red ginseng is well-known for various pharmacological
      activities, but most studies have been focused on red ginseng water extract
      (RGW), which has resulted in the conception of the present study of red ginseng
      oil (RGO) against Abeta25-35-induced neurotoxicity. Cytotoxicity and apoptosis
      induction by Abeta were verified and the underlying mechanism by which RGO
      inhibited neuronal cell death, mitochondria dysfunction and NF-kappaB pathway
      related protein markers were evaluated. RGO attenuated Abeta25-35-induced
      apoptosis, not only by inhibiting calcium influx, but also by reducing
      mitochondrial membrane potential loss. RGO significantly decreased Bax, whereas
      increased Bcl-2 and inactivated of caspase-3 and -9 and PARP-1 stimulated by
      Abeta25-35. Anti-neuroinflammatory effect of RGO was demonstrated by
      downregulating c-Jun N-terminal kinase (JNK) and p38, resulting in inhibiting of
      the NF-kappaB pathway and thereby suppressing the expressions of pro-inflammatory
      mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX
      2), prostaglandin E2 (PGE2), nitric oxide (NO) and tumor necrosis factor-alpha
      (TNF-alpha). The present study revealed that RGO is a potential natural resource
      of the functional foods industry as well as a promising candidate of multi-target
      neuronal protective agent for the prevention of AD.

PMID- 29065559
TI  - Effect of Nano-CuO on Engineering and Microstructure Properties of Fibre
      Reinforced Mortars Incorporating Metakaolin: Experimental and Numerical Studies.
AB  - In this study, the effects of nano-CuO (NC) on engineering properties of fibre
      reinforced mortars incorporating metakaolin (MK) were investigated. The effects
      of polypropylene fibre (PP) were also examined. A total of twenty-six mixtures
      were prepared. The experimental results were compared with numerical results
      obtained by adaptive neuro-fuzzy inference system (ANFIS) and Primal Estimated
      sub-GrAdient Solver for SVM (Pegasos) algorithm. Scanning Electron Microscope
      (SEM) was also employed to investigate the microstructure of the cement matrix.
      The mechanical test results showed that both compressive and flexural strengths
      of cement mortars decreased with the increase of MK content, however the strength
      values increased significantly with increasing NC content in the mixture. The
      water absorption of samples decreased remarkably with increasing NC particles in
      the mixture. When PP fibres were added, the strengths of cement mortars were
      further enhanced accompanied with lower water absorption values. The addition of
      2 wt % and 3 wt % nanoparticles in cement mortar led to a positive contribution
      to strength and resistance to water absorption. Mixture of PP-MK10NC3 indicated
      the best results for both compressive and flexural strengths at 28 and 90 days.
      SEM images illustrated that the morphology of cement matrix became more porous
      with increasing MK content, but the porosity reduced with the inclusion of NC. In
      addition, it is evident from the SEM images that more cement hydration products
      adhered onto the surface of fibres, which would improve the fibre-matrix
      interface. The numerical results obtained by ANFIS and Pegasos were close to the
      experimental results. The value of R2 obtained for each data set (validate, test
      and train) was higher than 0.90 and the values of mean absolute percentage error
      (MAPE) and the relative root mean squared error (PRMSE) were near zero. The ANFIS
      and Pegasos models can be used to predict the mechanical properties and water
      absorptions of fibre-reinforced mortars with MK and NC.

PMID- 29065560
TI  - A Search-and-Rescue Robot System for Remotely Sensing the Underground Coal Mine
      Environment.
AB  - This paper introduces a search-and-rescue robot system used for remote sensing of
      the underground coal mine environment, which is composed of an operating control
      unit and two mobile robots with explosion-proof and waterproof function. This
      robot system is designed to observe and collect information of the coal mine
      environment through remote control. Thus, this system can be regarded as a
      multifunction sensor, which realizes remote sensing. When the robot system
      detects danger, it will send out signals to warn rescuers to keep away. The robot
      consists of two gas sensors, two cameras, a two-way audio, a 1 km-long fiber
      optic cable for communication and a mechanical explosion-proof manipulator.
      Especially, the manipulator is a novel explosion-proof manipulator for cleaning
      obstacles, which has 3-degree-of-freedom, but is driven by two motors.
      Furthermore, the two robots can communicate in series for 2 km with the operating
      control unit. The development of the robot system may provide a reference for
      developing future search-and-rescue systems.

PMID- 29065561
TI  - Cl-Assisted Large Scale Synthesis of Cm-Scale Buckypapers of Fe3C-Filled Carbon
      Nanotubes with Pseudo-Capacitor Properties: The Key Role of SBA-16 Catalyst
      Support as Synthesis Promoter.
AB  - We show a novel chemical vapour deposition (CVD) approach, in which the large
      scale fabrication of ferromagnetically-filled cm-scale buckypapers is achieved
      through the deposition of a mesoporous supported catalyst (SBA-16) on a silicon
      substrate. We demonstrate that SBA-16 has the crucial role of promoting the
      growth of carbon nanotubes (CNTs) on a horizontal plane with random orientation
      rather than in a vertical direction, therefore allowing a facile fabrication of
      cm-scale CNTs buckypapers free from the onion-crust by-product observed on the
      buckypaper-surface in previous reports. The morphology and composition of the
      obtained CNTs-buckypapers are analyzed in detail by scanning electron microscopy
      (SEM), Energy Dispersive X-ray (EDX), transmission electron microscopy (TEM),
      high resolution TEM (HRTEM), and thermogravimetric analysis (TGA), while
      structural analysis is performed by Rietveld Refinement of XRD data. The room
      temperature magnetic properties of the produced buckypapers are also investigated
      and reveal the presence of a high coercivity of 650 Oe. Additionally, the
      electrochemical performances of these buckypapers are demonstrated and reveal a
      behavior that is compatible with that of a pseudo-capacitor (resistive-capacitor)
      with better performances than those presented in other previously studied layered
      buckypapers of Fe-filled CNTs, obtained by pyrolysis of dichlorobenzene-ferrocene
      mixtures. These measurements indicate that these materials show promise for
      applications in energy storage systems as flexible electrodes.

PMID- 29065558
TI  - The Interactive Roles of Lipopolysaccharides and dsRNA/Viruses on Respiratory
      Epithelial Cells and Dendritic Cells in Allergic Respiratory Disorders: The
      Hygiene Hypothesis.
AB  - The original hygiene hypothesis declares "more infections in early childhood
      protect against later atopy". According to the hygiene hypothesis, the increased
      incidence of allergic disorders in developed countries is explained by the
      decrease of infections. Epithelial cells and dendritic cells play key roles in
      bridging the innate and adaptive immune systems. Among the various pattern
      recognition receptor systems of epithelial cells and dendritic cells, including
      toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like
      receptors (NLRs) and others, TLRs are the key systems of immune response
      regulation. In humans, TLRs consist of TLR1 to TLR10. They regulate cellular
      responses through engagement with TLR ligands, e.g., lipopolysaccharides (LPS)
      acts through TLR4 and dsRNA acts through TLR3, but there are certain common
      components between these two TLR pathways. dsRNA activates epithelial cells and
      dendritic cells in different directions, resulting in allergy-related Th2-skewing
      tendency in epithelial cells, and Th1-skewing tendency in dendritic cells. The
      Th2-skewing effect by stimulation of dsRNA on epithelial cells could be
      suppressed by the presence of LPS above some threshold. When LPS level decreases,
      the Th2-skewing effect increases. It may be via these interrelated networks and
      related factors that LPS modifies the allergic responses and provides a plausible
      mechanism of the hygiene hypothesis. Several hygiene hypothesis-related
      phenomena, seemingly conflicting, are also discussed in this review, along with
      their proposed mechanisms.

PMID- 29065564
TI  - Assessing Lightning and Wildfire Hazard by Land Properties and Cloud to Ground
      Lightning Data with Association Rule Mining in Alberta, Canada.
AB  - Hotspot analysis was implemented to find regions in the province of Alberta
      (Canada) with high frequency Cloud to Ground (CG) lightning strikes clustered
      together. Generally, hotspot regions are located in the central, central east,
      and south central regions of the study region. About 94% of annual lightning
      occurred during warm months (June to August) and the daily lightning frequency
      was influenced by the diurnal heating cycle. The association rule mining
      technique was used to investigate frequent CG lightning patterns, which were
      verified by similarity measurement to check the patterns' consistency. The
      similarity coefficient values indicated that there were high correlations
      throughout the entire study period. Most wildfires (about 93%) in Alberta
      occurred in forests, wetland forests, and wetland shrub areas. It was also found
      that lightning and wildfires occur in two distinct areas: frequent wildfire
      regions with a high frequency of lightning, and frequent wild-fire regions with a
      low frequency of lightning. Further, the preference index (PI) revealed locations
      where the wildfires occurred more frequently than in other class regions. The
      wildfire hazard area was estimated with the CG lightning hazard map and specific
      land use types.

PMID- 29065565
TI  - Enabling Health Reform through Regional Health Information Exchange: A Model
      Study from China.
AB  - Objective. To investigate and share the major challenges and experiences of
      building a regional health information exchange system in China in the context of
      health reform. Methods. This study used interviews, focus groups, a field study,
      and a literature review to collect insights and analyze data. The study examined
      Xinjin's approach to developing and implementing a health information exchange
      project, using exchange usage data for analysis. Results. Within three years and
      after spending approximately $2.4 million (15 million RMB), Xinjin County was
      able to build a complete, unified, and shared information system and many
      electronic health record components to integrate and manage health resources for
      198 health institutions in its jurisdiction, thus becoming a model of regional
      health information exchange for facilitating health reform. Discussion. Costs,
      benefits, experiences, and lessons were discussed, and the unique characteristics
      of the Xinjin case and a comparison with US cases were analyzed. Conclusion. The
      Xinjin regional health information exchange system is different from most of the
      others due to its government-led, government-financed approach. Centralized and
      coordinated efforts played an important role in its operation. Regional health
      information exchange systems have been proven critical for meeting the global
      challenges of health reform.

PMID- 29065563
TI  - Silver Nanoparticles Stabilised by Cationic Gemini Surfactants with Variable
      Spacer Length.
AB  - The present study is focused on the synthesis and investigation of the
      physicochemical and biological properties of silver nanoparticles stabilized with
      a series of cationic gemini surfactants having a polymethylene spacer of variable
      length. UV-VIS spectroscopy, dynamic light scattering, scanning electron
      microscopy and zeta potential measurements were applied to provide
      physicochemical characterization of the silver nanoparticles. The mean size
      values of the nanoparticles were found to be in the 50 to 115 nm range. From the
      nanoparticle size distributions and scanning electron microscopy images it
      results that a population of small nanoparticles with the size of several
      nanometers was confirmed if the nanoparticles were stabilized with gemini
      molecules with either a short methylene spacer (two or four -CH2- groups) or a
      long spacer (12 -CH2- groups). The average zeta potential value for silver
      nanoparticles stabilized with gemini molecules is roughly independent of gemini
      surfactant spacer length and is approx. +58 mV. An interaction model between
      silver nanoparticles and gemini molecules which reflects the gained experimental
      data, is suggested. Microbicidal activity determinations revealed that the silver
      nanoparticles stabilized with gemini surfactants are more efficient against Gram
      negative bacteria and yeasts, which has a direct relation to the interaction
      mechanism of nanoparticles with the bacterial cell membrane and its structural
      composition.

PMID- 29065567
TI  - Study of the Mechanical Environment of Chondrocytes in Articular Cartilage
      Defects Repaired Area under Cyclic Compressive Loading.
AB  - COMSOL finite element software was used to establish a solid-liquid coupling
      biphasic model of articular cartilage and a microscopic model of chondrocytes,
      using modeling to take into account the shape and number of chondrocytes in
      cartilage lacuna in each layer. The effects of cyclic loading at different
      frequencies on the micromechanical environment of chondrocytes in different
      regions of the cartilage were studied. The results showed that low frequency
      loading can cause stress concentration of superficial chondrocytes. Moreover,
      along with increased frequency, the maximum value of stress response curve of
      chondrocytes decreased, while the minimum value increased. When the frequency was
      greater than 0.2 Hz, the extreme value stress of response curve tended to be
      constant. Cyclic loading had a large influence on the distribution of liquid
      pressure in chondrocytes in the middle and deep layers. The concentration of
      fluid pressure changed alternately from intracellular to peripheral in the middle
      layer. Both the range of liquid pressure in the upper chondrocytes and the
      maximum value of liquid pressure in the lower chondrocytes in the same lacunae
      varied greatly in the deep layer. At the same loading frequency, the elastic
      modulus of artificial cartilage had little effect on the mechanical environment
      of chondrocytes.

PMID- 29065562
TI  - Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events.
AB  - There is a growing body of evidence documenting probiotic bacteria to have a
      beneficial effect to the host through their ability to modulate the mucosal
      immune system. Many probiotic bacteria can be considered to act as either immune
      activators or immune suppressors, which have appreciable influence on
      homeostasis, inflammatory- and suppressive-immunopathology. What is becoming
      apparent is the ability of these probiotics to modulate innate immune responses
      via direct or indirect effects on the signaling pathways that drive these
      activatory or suppressive/tolerogenic mechanisms. This review will focus on the
      immunomodulatory role of probiotics on signaling pathways in innate immune cells:
      from positive to negative regulation associated with innate immune cells driving
      gut mucosal functionality. Research investigations have shown probiotics to
      modulate innate functionality in many ways including, receptor antagonism,
      receptor expression, binding to and expression of adaptor proteins, expression of
      negative regulatory signal molecules, induction of micro-RNAs, endotoxin
      tolerisation and finally, the secretion of immunomodulatory proteins, lipids and
      metabolites. The detailed understanding of the immunomodulatory signaling effects
      of probiotic strains will facilitate strain-specific selective manipulation of
      innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune
      deviation and tolerisation in both healthy subjects and patients with
      inflammatory and suppressive pathology.

PMID- 29065566
TI  - Upper Limb Rehabilitation Robot Powered by PAMs Cooperates with FES Arrays to
      Realize Reach-to-Grasp Trainings.
AB  - The reach-to-grasp activities play an important role in our daily lives. The
      developed RUPERT for stroke patients with high stiffness in arm flexor muscles is
      a low-cost lightweight portable exoskeleton rehabilitation robot whose joints are
      unidirectionally actuated by pneumatic artificial muscles (PAMs). In order to
      expand the useful range of RUPERT especially for patients with flaccid paralysis,
      functional electrical stimulation (FES) is taken to activate paralyzed arm
      muscles. As both the exoskeleton robot driven by PAMs and the neuromuscular
      skeletal system under FES possess the highly nonlinear and time-varying
      characteristics, iterative learning control (ILC) is studied and is taken to
      control this newly designed hybrid rehabilitation system for reaching trainings.
      Hand function rehabilitation refers to grasping. Because of tiny finger muscles,
      grasping and releasing are realized by FES array electrodes and matrix scan
      method. By using the surface electromyography (EMG) technique, the subject's
      active intent is identified. The upper limb rehabilitation robot powered by PAMs
      cooperates with FES arrays to realize active reach-to-grasp trainings, which was
      verified through experiments.

PMID- 29065568
TI  - Handling Data Skew in MapReduce Cluster by Using Partition Tuning.
AB  - The healthcare industry has generated large amounts of data, and analyzing these
      has emerged as an important problem in recent years. The MapReduce programming
      model has been successfully used for big data analytics. However, data skew
      invariably occurs in big data analytics and seriously affects efficiency. To
      overcome the data skew problem in MapReduce, we have in the past proposed a data
      processing algorithm called Partition Tuning-based Skew Handling (PTSH). In
      comparison with the one-stage partitioning strategy used in the traditional
      MapReduce model, PTSH uses a two-stage strategy and the partition tuning method
      to disperse key-value pairs in virtual partitions and recombines each partition
      in case of data skew. The robustness and efficiency of the proposed algorithm
      were tested on a wide variety of simulated datasets and real healthcare datasets.
      The results showed that PTSH algorithm can handle data skew in MapReduce
      efficiently and improve the performance of MapReduce jobs in comparison with the
      native Hadoop, Closer, and locality-aware and fairness-aware key partitioning
      (LEEN). We also found that the time needed for rule extraction can be reduced
      significantly by adopting the PTSH algorithm, since it is more suitable for
      association rule mining (ARM) on healthcare data.

PMID- 29065569
TI  - New Directions in 3D Medical Modeling: 3D-Printing Anatomy and Functions in
      Neurosurgical Planning.
AB  - This paper illustrates the feasibility and utility of combining cranial anatomy
      and brain function on the same 3D-printed model, as evidenced by a neurosurgical
      planning case study of a 29-year-old female patient with a low-grade frontal-lobe
      glioma. We herein report the rapid prototyping methodology utilized in
      conjunction with surgical navigation to prepare and plan a complex neurosurgery.
      The method introduced here combines CT and MRI images with DTI tractography,
      while using various image segmentation protocols to 3D model the skull base,
      tumor, and five eloquent fiber tracts. This 3D model is rapid-prototyped and
      coregistered with patient images and a reported surgical navigation system,
      establishing a clear link between the printed model and surgical navigation. This
      methodology highlights the potential for advanced neurosurgical preparation,
      which can begin before the patient enters the operation theatre. Moreover, the
      work presented here demonstrates the workflow developed at the National
      University Hospital of Iceland, Landspitali, focusing on the processes of anatomy
      segmentation, fiber tract extrapolation, MRI/CT registration, and 3D printing.
      Furthermore, we present a qualitative and quantitative assessment for fiber tract
      generation in a case study where these processes are applied in the preparation
      of brain tumor resection surgery.

PMID- 29065571
TI  - Research on Safety and Compliance of a New Lower Limb Rehabilitation Robot.
AB  - The lower limb rehabilitation robot is an application of robotic technology for
      stroke people with lower limb disabilities. A new applicable and effective
      sitting/lying lower limb rehabilitation robot (LLR-Ro) is proposed, which has the
      mechanical limit protection, the electrical limit protection, and the software
      protection to prevent the patient from the secondary damage. Meanwhile, as a new
      type of the rehabilitation robots, its hip joint rotation ranges are different in
      the patient sitting training posture and lying training posture. The mechanical
      leg of the robot has a variable workspace to work in both training postures. So,
      if the traditional mechanical limit and the electrical limit cannot be used in
      the hip joint mechanism design, a follow-up limit is first proposed to improve
      the compatibility of human-machine motion. Besides, to eliminate the accident
      interaction force between the patient and LLR-Ro in the process of the passive
      training, an amendment impedance control strategy based on the position control
      is proposed to improve the compliance of the LLR-Ro. A simulation experiment and
      an experiment with a participant show that the passive training of LLR-Ro has
      compliance.

PMID- 29065570
TI  - A Numerical Investigation into the Effects of Overweight and Obesity on Total
      Knee Arthroplasty.
AB  - Overweight and obesity increase risks of knee osteoarthritis, which is a major
      cause of disability. Severe knee osteoarthritis can be treated by knee
      arthroplasty. Total knee arthroplasty has been used in overweight and obese
      patients; however, clinical reports showed that the outcome of this group of
      patients was not good as normal-weight patients. Two computer models were created
      in this paper to simulate the effect of excess loads on the distal femoral bone
      and contact pressures in total knee arthroplasty during a gait cycle. The
      numerical results showed increased stress in periprosthetic distal femoral bones
      and higher contact pressure on tibial polyethylene insert during the stance
      phase. Based on the computer simulation results and published research work,
      cementless total knee arthroplasty with thicker tibial polyethylene insert may be
      a better option for overweight patients.

PMID- 29065572
TI  - A Strain Feedback Compensation Method during Cell Tensile Experiments.
AB  - Cell tensile technique is an important and widely used tool in cell mechanical
      research. However, the strain control condition in traditional tensile
      experiments is not satisfied and would result in big errors. These strain errors
      will seriously impact the experimental accuracy and decrease the reliability and
      comparability of experimental results. In order to achieve the accurate strain
      control of the membrane during stretching, a strain feedback compensation method
      based on the digital image correlation is proposed in this paper. To evaluate the
      effect of the proposed compensation method, a series of stretching experiments in
      different strains ranging from 5% to 20% were performed. The results showed that
      our proposed method significantly decreased the errors of strain control. These
      results indicate that the strain feedback compensation method is very effective
      in controlling strain and can greatly improve the experimental accuracy.

PMID- 29065573
TI  - Robotics in Biomedical and Healthcare Engineering.

PMID- 29065574
TI  - Quantitative Analysis of Intracellular Motility Based on Optical Flow Model.
AB  - Analysis of cell mobility is a key issue for abnormality identification and
      classification in cell biology research. However, since cell deformation induced
      by various biological processes is random and cell protrusion is irregular, it is
      difficult to measure cell morphology and motility in microscopic images. To
      address this dilemma, we propose an improved variation optical flow model for
      quantitative analysis of intracellular motility, which not only extracts
      intracellular motion fields effectively but also deals with optical flow
      computation problem at the border by taking advantages of the formulation based
      on L1 and L2 norm, respectively. In the energy functional of our proposed optical
      flow model, the data term is in the form of L2 norm; the smoothness of the data
      changes with regional features through an adaptive parameter, using L1 norm near
      the edge of the cell and L2 norm away from the edge. We further extract
      histograms of oriented optical flow (HOOF) after optical flow field of
      intracellular motion is computed. Then distances of different HOOFs are
      calculated as the intracellular motion features to grade the intracellular
      motion. Experimental results show that the features extracted from HOOFs provide
      new insights into the relationship between the cell motility and the special
      pathological conditions.

PMID- 29065575
TI  - Inertial Sensor-Based Motion Analysis of Lower Limbs for Rehabilitation
      Treatments.
AB  - The hemiplegic rehabilitation state diagnosing performed by therapists can be
      biased due to their subjective experience, which may deteriorate the
      rehabilitation effect. In order to improve this situation, a quantitative
      evaluation is proposed. Though many motion analysis systems are available, they
      are too complicated for practical application by therapists. In this paper, a
      method for detecting the motion of human lower limbs including all degrees of
      freedom (DOFs) via the inertial sensors is proposed, which permits analyzing the
      patient's motion ability. This method is applicable to arbitrary walking
      directions and tracks of persons under study, and its results are unbiased, as
      compared to therapist qualitative estimations. Using the simplified mathematical
      model of a human body, the rotation angles for each lower limb joint are
      calculated from the input signals acquired by the inertial sensors. Finally, the
      rotation angle versus joint displacement curves are constructed, and the
      estimated values of joint motion angle and motion ability are obtained. The
      experimental verification of the proposed motion detection and analysis method
      was performed, which proved that it can efficiently detect the differences
      between motion behaviors of disabled and healthy persons and provide a reliable
      quantitative evaluation of the rehabilitation state.

PMID- 29065576
TI  - A SOA-Based Platform to Support Clinical Data Sharing.
AB  - The eSource Data Interchange Group, part of the Clinical Data Interchange
      Standards Consortium, proposed five scenarios to guide stakeholders in the
      development of solutions for the capture of eSource data. The fifth scenario was
      subdivided into four tiers to adapt the functionality of electronic health
      records to support clinical research. In order to develop a system belonging to
      the "Interoperable" Tier, the authors decided to adopt the service-oriented
      architecture paradigm to support technical interoperability, Health Level Seven
      Version 3 messages combined with LOINC (Logical Observation Identifiers Names and
      Codes) vocabulary to ensure semantic interoperability, and Healthcare Services
      Specification Project standards to provide process interoperability. The
      developed architecture enhances the integration between patient-care practice and
      medical research, allowing clinical data sharing between two hospital information
      systems and four clinical data management systems/clinical registries. The core
      is formed by a set of standardized cloud services connected through standardized
      interfaces, involving client applications. The system was approved by a medical
      staff, since it reduces the workload for the management of clinical trials.
      Although this architecture can realize the "Interoperable" Tier, the current
      solution actually covers the "Connected" Tier, due to local hospital policy
      restrictions.

PMID- 29065577
TI  - Experimental Study on the Mechanical Properties of Porcine Cartilage with
      Microdefect under Rolling Load.
AB  - OBJECTIVES: To investigate the mechanical responses of microdefect articular
      cartilage under rolling load and find out the failure rule. METHODS: Rolling load
      was applied to the porcine articular cartilage samples with rectangular notches
      of different depths. The displacement and strain near the notches were obtained
      by the noncontact digital image correlation technique. RESULTS: The strain value
      and peak frequency around the notch increased; the maximum equivalent strain
      value could be observed at both bottom corners of the notch; the equivalent
      strain value first increased and then decreased at the points in the superficial
      and middle layers with the increase of rolling velocity; the points in the deep
      layer were less affected by rolling velocity; the equivalent strain value of the
      points in the superficial layer declined after rising with the increase of defect
      depth, while a decreased trend could be found for the points in the middle and
      deep layers. CONCLUSIONS: The shear strain, which rose with the increase in
      defect depth, was the main factor in cartilage destruction. The cartilage tended
      to be destructed firstly at the bottom corner of the defect. Rolling velocity
      showed significant effects on superficial and middle layers. Cartilage had the
      ability to resist destruction.

PMID- 29065578
TI  - Axiomatic Design of a Framework for the Comprehensive Optimization of Patient
      Flows in Hospitals.
AB  - Lean Management and Six Sigma are nowadays applied not only to the manufacturing
      industry but also to service industry and public administration. The manifold
      variables affecting the Health Care system minimize the effect of a narrow Lean
      intervention. Therefore, this paper aims to discuss a comprehensive, system-based
      approach to achieve a factual holistic optimization of patient flows. This paper
      debates the efficacy of Lean principles applied to the optimization of patient
      flows and related activities, structures, and resources, developing a theoretical
      framework based on the principles of the Axiomatic Design. The demand for patient
      oriented and efficient health services leads to use these methodologies to
      improve hospital processes. In the framework, patients with similar
      characteristics are clustered in families to achieve homogeneous flows through
      the value stream. An optimization checklist is outlined as the result of the
      mapping between Functional Requirements and Design Parameters, with the right
      sequence of the steps to optimize the patient flow according to the principles of
      Axiomatic Design. The Axiomatic Design-based top-down implementation of Health
      Care evidence, according to Lean principles, results in a holistic optimization
      of hospital patient flows, by reducing the complexity of the system.

PMID- 29065579
TI  - Mechanical Bed for Investigating Sleep-Inducing Vibration.
AB  - In running cars or trains, passengers often feel sleepy. Our study focuses on
      this physiological phenomenon. If a machine can reproduce this phenomenon, it is
      feasible to put a person, such as an insomnia patient or an infant, to sleep
      without any harmful effects. The results of our previous study suggest that low
      frequency vibration induces sleep. This report describes a new mechanical bed for
      inducing sleep and discusses the effects of different vibration conditions. The
      new bed has two active DOFs in the vertical and horizontal directions to examine
      the anisotropy of sensation. The bed includes three main parts: a vertical driver
      unit, a horizontal driver unit, and a unique 2-DOF counterweight system to reduce
      driving force and noise. With regard to motion accuracy, the maximum motion error
      in the vertical direction lifting 75 kg load was only 0.06 mm with a 5.0 mm
      amplitude of a 0.5 Hz sinusoidal wave. The results of excitation experiments with
      10 subjects showed a significant difference in sleep latency between the
      conditions with vibration and without vibration. Furthermore, the average latency
      with insensible vibration (amplitude = 2.4 mm) was shorter than that with
      sensible vibration (amplitude = 7.5 mm). These results suggest the ability of
      appropriate vibration to induce sleep.

PMID- 29065580
TI  - An Interpretable Classification Framework for Information Extraction from Online
      Healthcare Forums.
AB  - Online healthcare forums (OHFs) have become increasingly popular for patients to
      share their health-related experiences. The healthcare-related texts posted in
      OHFs could help doctors and patients better understand specific diseases and the
      situations of other patients. To extract the meaning of a post, a commonly used
      way is to classify the sentences into several predefined categories of different
      semantics. However, the unstructured form of online posts brings challenges to
      existing classification algorithms. In addition, though many sophisticated
      classification models such as deep neural networks may have good predictive
      power, it is hard to interpret the models and the prediction results, which is,
      however, critical in healthcare applications. To tackle the challenges above, we
      propose an effective and interpretable OHF post classification framework.
      Specifically, we classify sentences into three classes: medication, symptom, and
      background. Each sentence is projected into an interpretable feature space
      consisting of labeled sequential patterns, UMLS semantic types, and other
      heuristic features. A forest-based model is developed for categorizing OHF posts.
      An interpretation method is also developed, where the decision rules can be
      explicitly extracted to gain an insight of useful information in texts.
      Experimental results on real-world OHF data demonstrate the effectiveness of our
      proposed computational framework.

PMID- 29065582
TI  - An Evaluation of the Benefits of Simultaneous Acquisition on PET/MR
      Coregistration in Head/Neck Imaging.
AB  - Coregistration of multimodal diagnostic images is crucial for qualitative and
      quantitative multiparametric analysis. While retrospective coregistration is
      computationally intense and could be inaccurate, hybrid PET/MR scanners allow
      acquiring implicitly coregistered images. Aim of this study is to assess the
      performance of state-of-the-art coregistration methods applied to PET and MR
      acquired as single modalities, comparing the results with the implicitly
      coregistration of a hybrid PET/MR, in complex anatomical regions such as
      head/neck (HN). A dataset consisting of PET/CT and PET/MR subsequently acquired
      in twenty-three patients was considered: performance of rigid (RR) and deformable
      (DR) registration obtained by a commercial software and an open-source
      registration package was evaluated. Registration accuracy was qualitatively
      assessed in terms of visual alignment of anatomical structures and qualitatively
      measured by the Dice scores computed on segmented tumors in PET and MRI. The
      resulting scores highlighted that hybrid PET/MR showed higher registration
      accuracy than retrospectively coregistered images, because of an overall
      misalignment after RR, unrealistic deformations and volume variations after DR.
      DR revealed superior performance compared to RR due to complex nonrigid movements
      of HN district. Moreover, simultaneous PET/MR offers unique datasets serving as
      ground truth for the improvement and validation of coregistration algorithms, if
      acquired with PET/CT.

PMID- 29065581
TI  - Low-Frequency Pulsed Electromagnetic Field Is Able to Modulate miRNAs in an
      Experimental Cell Model of Alzheimer's Disease.
AB  - The aim of the present study was to investigate on the effects of a low-frequency
      pulsed electromagnetic field (LF-PEMF) in an experimental cell model of
      Alzheimer's disease (AD) to assess new therapies that counteract
      neurodegeneration. In recent scientific literature, it is documented that the
      deep brain stimulation via electromagnetic fields (EMFs) modulates the
      neurophysiological activity of the pathological circuits and produces clinical
      benefits in AD patients. EMFs are applied for tissue regeneration because of
      their ability to stimulate cell proliferation and immune functions via the HSP70
      protein family. However, the effects of EMFs are still controversial and further
      investigations are required. Our results demonstrate the ability of our LF-PEMF
      to modulate gene expression in cell functions that are dysregulated in AD (i.e.,
      BACE1) and that these effects can be modulated with different treatment
      conditions. Of relevance, we will focus on miRNAs regulating the pathways
      involved in brain degenerative disorders.

PMID- 29065584
TI  - The Influence of Natural Head Position on the Cervical Sagittal Alignment.
AB  - INTRODUCTION: This study investigated the relationship between the parameters
      related to the natural head position and cervical segmental angles and alignment
      of patients with neck pain. MATERIAL AND METHODS: The lateral radiographs of the
      cervical spine were collected from 103 patients and were used to retrospectively
      analyze the correlation between the natural head position, cervical local
      sagittal angles, and alignment. Sagittal measurements were as follows: cervical
      curvature classification, slope of McGregor's line (McGS), local sagittal angles
      (C0-C2 angle, C2-C5 angle, C5-C7 angle, and C2-C7 angle), T1 slope, center of
      gravity of the head to sagittal vertical axis (CG-C7 SVA), and local sagittal
      alignment (C0-C2 SVA and C2-C7 SVA). RESULTS: McGS was significantly correlated
      to C0-C2 angle (r = 0.57), C0-C2 SVA (r = -0.53), C2-C7 SVA (r = -0.28), and CG
      C7 SVA (r = -0.47). CG-C7 SVA was also significantly correlated to curvature type
      (r = 0.27), C5-C7 angle (r = -0.37), and C2-C7 angle (r = -0.39). CONCLUSIONS: A
      backward shift with an extended head position may accompany a relatively normal
      curvature of the cervical spine. The effect of posture control in relieving
      abnormal mechanical state of the cervical spine needs to be further confirmed by
      biomechanical analysis.

PMID- 29065583
TI  - Neural Network-Based Coronary Heart Disease Risk Prediction Using Feature
      Correlation Analysis.
AB  - BACKGROUND: Of the machine learning techniques used in predicting coronary heart
      disease (CHD), neural network (NN) is popularly used to improve performance
      accuracy. OBJECTIVE: Even though NN-based systems provide meaningful results
      based on clinical experiments, medical experts are not satisfied with their
      predictive performances because NN is trained in a "black-box" style. METHOD: We
      sought to devise an NN-based prediction of CHD risk using feature correlation
      analysis (NN-FCA) using two stages. First, the feature selection stage, which
      makes features acceding to the importance in predicting CHD risk, is ranked, and
      second, the feature correlation analysis stage, during which one learns about the
      existence of correlations between feature relations and the data of each NN
      predictor output, is determined. RESULT: Of the 4146 individuals in the Korean
      dataset evaluated, 3031 had low CHD risk and 1115 had CHD high risk. The area
      under the receiver operating characteristic (ROC) curve of the proposed model
      (0.749 +/- 0.010) was larger than the Framingham risk score (FRS) (0.393 +/-
      0.010). CONCLUSIONS: The proposed NN-FCA, which utilizes feature correlation
      analysis, was found to be better than FRS in terms of CHD risk prediction.
      Furthermore, the proposed model resulted in a larger ROC curve and more accurate
      predictions of CHD risk in the Korean population than the FRS.

PMID- 29065585
TI  - A Review on Human Activity Recognition Using Vision-Based Method.
AB  - Human activity recognition (HAR) aims to recognize activities from a series of
      observations on the actions of subjects and the environmental conditions. The
      vision-based HAR research is the basis of many applications including video
      surveillance, health care, and human-computer interaction (HCI). This review
      highlights the advances of state-of-the-art activity recognition approaches,
      especially for the activity representation and classification methods. For the
      representation methods, we sort out a chronological research trajectory from
      global representations to local representations, and recent depth-based
      representations. For the classification methods, we conform to the categorization
      of template-based methods, discriminative models, and generative models and
      review several prevalent methods. Next, representative and available datasets are
      introduced. Aiming to provide an overview of those methods and a convenient way
      of comparing them, we classify existing literatures with a detailed taxonomy
      including representation and classification methods, as well as the datasets they
      used. Finally, we investigate the directions for future research.

PMID- 29065586
TI  - A Method for Assessing the Retention of Trace Elements in Human Body Using Neural
      Network Technology.
AB  - Models that describe the trace element status formation in the human organism are
      essential for a correction of micromineral (trace elements) deficiency. A direct
      trace element retention assessment in the body is difficult due to the many
      internal mechanisms. The trace element retention is determined by the amount and
      the ratio of incoming and excreted substance. So, the concentration of trace
      elements in drinking water characterizes the intake, whereas the element
      concentration in urine characterizes the excretion. This system can be
      interpreted as three interrelated elements that are in equilibrium. Since many
      relationships in the system are not known, the use of standard mathematical
      models is difficult. The artificial neural network use is suitable for
      constructing a model in the best way because it can take into account all
      dependencies in the system implicitly and process inaccurate and incomplete data.
      We created several neural network models to describe the retentions of trace
      elements in the human body. On the model basis, we can calculate the microelement
      levels in the body, knowing the trace element levels in drinking water and urine.
      These results can be used in health care to provide the population with safe
      drinking water.

PMID- 29065587
TI  - Endogenous Production of n-3 Polyunsaturated Fatty Acids Promotes Fracture
      Healing in Mice.
AB  - Bone fracture is a global healthcare issue for high rates of delayed healing and
      nonunions. Although n-3 polyunsaturated fatty acid (PUFA) is considered as a
      beneficial factor for bone metabolism, only few studies till date focused on the
      effects of n-3 PUFAs on fracture healing. In this study, we investigated the
      effect of endogenous n-3 PUFAs on fracture healing by measuring femur fracture
      repair in both fat-1 transgenic mice and WT mice. Proximal femoral fracture model
      was established in fat-1 transgenic mice and WT mice, respectively, and then the
      fracture was analyzed by using X-ray, micro-computed tomography (micro-CT), and
      histological assessment at 7, 14, 21, 28, and 35 days after fixation. The results
      showed that compared with WT mice, fat-1 mice exhibited acceleration in fracture
      healing through radiographic and histological analysis (18-21 days versus 21-28
      days postfracture). Meanwhile, X-ray and micro-CT analysis that showed better
      remodeling callus formation were in the fat-1 group compared to WT group.
      Furthermore, histological analysis revealed that endogenous n-3 PUFAs promoted
      local endochondral ossification and accelerated the remodeling of calcified
      calluses after fracture. In conclusion, the present study indicated that
      endogenously produced n-3 PUFAs promote fracture healing process and accelerate
      bone remodeling in mice, and supplementation of n-3 PUFAs was positively
      associated with fracture healing.

PMID- 29065588
TI  - Novel Passive Two-Stage Magnetic Targeting Devices for Distal Locking of
      Interlocking Nails.
AB  - Interlocking nailing is a common surgical operation to stabilize fractures in
      long bones. One of the difficult parts of the surgery is how to locate the
      position and direction of a screw hole on the interlocking nail, which is
      invisible to the naked eye after insertion of the nail into the medullary canal.
      Here, we propose a novel two-stage targeting process using two passive magnetic
      devices to locate the position and direction of the screw hole without radiation
      for the locking screw procedure. This involves a ring-shape positioning magnet
      inside the nail to generate a magnetic field for targeting. From the accuracy
      test results of these two-stage targeting devices, the search region can be
      identified in less than 20 seconds by the 1st-stage targeting device, while the
      total targeting time to locate the drilling position and direction takes less
      than 4 minutes, with 100% successful rate in 50 attempts. The drilling test
      further combines the two-stage targeting process and drilling process on the
      swine tibia, and it is shown that a 100% successful rate is achieved in all 10
      attempts, where the total time needed is less than 5 minutes.

PMID- 29065590
TI  - Development of Single-Channel Hybrid BCI System Using Motor Imagery and SSVEP.
AB  - Numerous EEG-based brain-computer interface (BCI) systems that are being
      developed focus on novel feature extraction algorithms, classification methods
      and combining existing approaches to create hybrid BCIs. Several recent studies
      demonstrated various advantages of hybrid BCI systems in terms of an improved
      accuracy or number of commands available for the user. But still, BCI systems are
      far from realization for daily use. Having high performance with less number of
      channels is one of the challenging issues that persists, especially with hybrid
      BCI systems, where multiple channels are necessary to record information from two
      or more EEG signal components. Therefore, this work proposes a single-channel (C3
      or C4) hybrid BCI system that combines motor imagery (MI) and steady-state
      visually evoked potential (SSVEP) approaches. This study demonstrates that
      besides MI features, SSVEP features can also be captured from C3 or C4 channel.
      The results show that due to rich feature information (MI and SSVEP) at these
      channels, the proposed hybrid BCI system outperforms both MI- and SSVEP-based
      systems having an average classification accuracy of 85.6 +/- 7.7% in a two-class
      task.

PMID- 29065589
TI  - The Electrode Modality Development in Pulsed Electric Field Treatment Facilitates
      Biocellular Mechanism Study and Improves Cancer Ablation Efficacy.
AB  - Pulsed electric field treatment is now widely used in diverse biological and
      medical applications: gene delivery, electrochemotherapy, and cancer therapy.
      This minimally invasive technique has several advantages over traditional
      ablation techniques, such as nonthermal elimination and blood vessel spare
      effect. Different electrodes are subsequently developed for a specific treatment
      purpose. Here, we provide a systematic review of electrode modality development
      in pulsed electric field treatment. For electrodes invented for experiment in
      vitro, sheet electrode and electrode cuvette, electrodes with high-speed
      fluorescence imaging system, electrodes with patch-clamp, and electrodes with
      confocal laser scanning microscopy are introduced. For electrodes invented for
      experiment in vivo, monopolar electrodes, five-needle array electrodes, single
      needle bipolar electrode, parallel plate electrodes, and suction electrode are
      introduced. The pulsed electric field provides a promising treatment for cancer.

PMID- 29065591
TI  - Semantic Modeling for Exposomics with Exploratory Evaluation in Clinical Context.
AB  - Exposome is a critical dimension in the precision medicine paradigm. Effective
      representation of exposomics knowledge is instrumental to melding nongenetic
      factors into data analytics for clinical research. There is still limited work in
      (1) modeling exposome entities and relations with proper integration to
      mainstream ontologies and (2) systematically studying their presence in clinical
      context. Through selected ontological relations, we developed a template-driven
      approach to identifying exposome concepts from the Unified Medical Language
      System (UMLS). The derived concepts were evaluated in terms of literature
      coverage and the ability to assist in annotating clinical text. The generated
      semantic model represents rich domain knowledge about exposure events (454 pairs
      of relations between exposure and outcome). Additionally, a list of 5667 disorder
      concepts with microbial etiology was created for inferred pathogen exposures. The
      model consistently covered about 90% of PubMed literature on exposure-induced
      iatrogenic diseases over 10 years (2001-2010). The model contributed to the
      efficiency of exposome annotation in clinical text by filtering out 78% of
      irrelevant machine annotations. Analysis into 50 annotated discharge summaries
      helped advance our understanding of the exposome information in clinical text.
      This pilot study demonstrated feasibility of semiautomatically developing a
      useful semantic resource for exposomics.

PMID- 29065592
TI  - A New Feature Ensemble with a Multistage Classification Scheme for Breast Cancer
      Diagnosis.
AB  - A new and effective feature ensemble with a multistage classification is proposed
      to be implemented in a computer-aided diagnosis (CAD) system for breast cancer
      diagnosis. A publicly available mammogram image dataset collected during the
      Image Retrieval in Medical Applications (IRMA) project is utilized to verify the
      suggested feature ensemble and multistage classification. In achieving the CAD
      system, feature extraction is performed on the mammogram region of interest (ROI)
      images which are preprocessed by applying a histogram equalization followed by a
      nonlocal means filtering. The proposed feature ensemble is formed by
      concatenating the local configuration pattern-based, statistical, and frequency
      domain features. The classification process of these features is implemented in
      three cases: a one-stage study, a two-stage study, and a three-stage study. Eight
      well-known classifiers are used in all cases of this multistage classification
      scheme. Additionally, the results of the classifiers that provide the top three
      performances are combined via a majority voting technique to improve the
      recognition accuracy on both two- and three-stage studies. A maximum of 85.47%,
      88.79%, and 93.52% classification accuracies are attained by the one-, two-, and
      three-stage studies, respectively. The proposed multistage classification scheme
      is more effective than the single-stage classification for breast cancer
      diagnosis.

PMID- 29065593
TI  - User-Centric Feedback for the Development and Review of a Unique Robotic Glove
      Prototype to Be Used in Therapy.
AB  - Disability can be a great impediment to daily living in later life and is often
      the result of illness or trauma. Modern thoughts on treatment are orientated
      towards the use of robotics; however, these are often designed without
      consultation with the user. This paper used a 5-point questionnaire to ask former
      therapy patients what they felt needed further improvements from potential
      robotics and what features of such a system were the most important. Significant
      emphasis was placed on helping them to grasp (M = 4.63) as well as having a
      functional use. They also desired a system with clearly distinguished (M = 4.22)
      and easy to operate controls (M = 4.44) whilst allowing them some freedom to move
      around independently (M = 4.44). This provided the rationale for a prototype dual
      layered vacuum glove that was sampled by healthcare staff to provide feedback
      that forms the basis for future improvements.

PMID- 29065594
TI  - The Edge Detectors Suitable for Retinal OCT Image Segmentation.
AB  - Retinal layer thickness measurement offers important information for reliable
      diagnosis of retinal diseases and for the evaluation of disease development and
      medical treatment responses. This task critically depends on the accurate edge
      detection of the retinal layers in OCT images. Here, we intended to search for
      the most suitable edge detectors for the retinal OCT image segmentation task. The
      three most promising edge detection algorithms were identified in the related
      literature: Canny edge detector, the two-pass method, and the EdgeFlow technique.
      The quantitative evaluation results show that the two-pass method outperforms
      consistently the Canny detector and the EdgeFlow technique in delineating the
      retinal layer boundaries in the OCT images. In addition, the mean localization
      deviation metrics show that the two-pass method caused the smallest edge shifting
      problem. These findings suggest that the two-pass method is the best among the
      three algorithms for detecting retinal layer boundaries. The overall better
      performance of Canny and two-pass methods over EdgeFlow technique implies that
      the OCT images contain more intensity gradient information than texture changes
      along the retinal layer boundaries. The results will guide our future efforts in
      the quantitative analysis of retinal OCT images for the effective use of OCT
      technologies in the field of ophthalmology.

PMID- 29065596
TI  - Cell Detection Using Extremal Regions in a Semisupervised Learning Framework.
AB  - This paper discusses an algorithm to build a semisupervised learning framework
      for detecting cells. The cell candidates are represented as extremal regions
      drawn from a hierarchical image representation. Training a classifier for cell
      detection using supervised approaches relies on a large amount of training data,
      which requires a lot of effort and time. We propose a semisupervised approach to
      reduce this burden. The set of extremal regions is generated using a maximally
      stable extremal region (MSER) detector. A subset of nonoverlapping regions with
      high similarity to the cells of interest is selected. Using the tree built from
      the MSER detector, we develop a novel differentiable unsupervised loss term that
      enforces the nonoverlapping constraint with the learned function. Our algorithm
      requires very few examples of cells with simple dot annotations for training. The
      supervised and unsupervised losses are embedded in a Bayesian framework for
      probabilistic learning.

PMID- 29065595
TI  - A Benchmark for Endoluminal Scene Segmentation of Colonoscopy Images.
AB  - Colorectal cancer (CRC) is the third cause of cancer death worldwide. Currently,
      the standard approach to reduce CRC-related mortality is to perform regular
      screening in search for polyps and colonoscopy is the screening tool of choice.
      The main limitations of this screening procedure are polyp miss rate and the
      inability to perform visual assessment of polyp malignancy. These drawbacks can
      be reduced by designing decision support systems (DSS) aiming to help clinicians
      in the different stages of the procedure by providing endoluminal scene
      segmentation. Thus, in this paper, we introduce an extended benchmark of
      colonoscopy image segmentation, with the hope of establishing a new strong
      benchmark for colonoscopy image analysis research. The proposed dataset consists
      of 4 relevant classes to inspect the endoluminal scene, targeting different
      clinical needs. Together with the dataset and taking advantage of advances in
      semantic segmentation literature, we provide new baselines by training standard
      fully convolutional networks (FCNs). We perform a comparative study to show that
      FCNs significantly outperform, without any further postprocessing, prior results
      in endoluminal scene segmentation, especially with respect to polyp segmentation
      and localization.

PMID- 29065597
TI  - Patient-Specific Deep Architectural Model for ECG Classification.
AB  - Heartbeat classification is a crucial step for arrhythmia diagnosis during
      electrocardiographic (ECG) analysis. The new scenario of wireless body sensor
      network- (WBSN-) enabled ECG monitoring puts forward a higher-level demand for
      this traditional ECG analysis task. Previously reported methods mainly addressed
      this requirement with the applications of a shallow structured classifier and
      expert-designed features. In this study, modified frequency slice wavelet
      transform (MFSWT) was firstly employed to produce the time-frequency image for
      heartbeat signal. Then the deep learning (DL) method was performed for the
      heartbeat classification. Here, we proposed a novel model incorporating automatic
      feature abstraction and a deep neural network (DNN) classifier. Features were
      automatically abstracted by the stacked denoising auto-encoder (SDA) from the
      transferred time-frequency image. DNN classifier was constructed by an encoder
      layer of SDA and a softmax layer. In addition, a deterministic patient-specific
      heartbeat classifier was achieved by fine-tuning on heartbeat samples, which
      included a small subset of individual samples. The performance of the proposed
      model was evaluated on the MIT-BIH arrhythmia database. Results showed that an
      overall accuracy of 97.5% was achieved using the proposed model, confirming that
      the proposed DNN model is a powerful tool for heartbeat pattern recognition.

PMID- 29065599
TI  - An Interactive Care System Based on a Depth Image and EEG for Aged Patients with
      Dementia.
AB  - Due to the limitations of the body movement and functional decline of the aged
      with dementia, they can hardly make an efficient communication with nurses by
      language and gesture language like a normal person. In order to improve the
      efficiency in the healthcare communication, an intelligent interactive care
      system is proposed in this paper based on a multimodal deep neural network (DNN).
      The input vector of the DNN includes motion and mental features and was extracted
      from a depth image and electroencephalogram that were acquired by Kinect and
      OpenBCI, respectively. Experimental results show that the proposed algorithm
      simplified the process of the recognition and achieved 96.5% and 96.4%,
      respectively, for the shuffled dataset and 90.9% and 92.6%, respectively, for the
      continuous dataset in terms of accuracy and recall rate.

PMID- 29065598
TI  - Heavy Metal Contamination in Soil and Brown Rice and Human Health Risk Assessment
      near Three Mining Areas in Central China.
AB  - BACKGROUND: Metal mining and waste discharge lead to regional heavy metal
      contamination and attract major concern because of the potential risk to local
      residents. METHODS: This research was conducted to determine lead (Pb), cadmium
      (Cd), arsenic (As), manganese (Mn), and antimony (Sb) concentrations in soil and
      brown rice samples from three heavy metal mining areas in Hunan Province, central
      China, and to assess the potential health risks to local inhabitants. RESULTS:
      Local soil contamination was observed, with mean concentrations of Cd, Pb, Sb,
      and As of 0.472, 193.133, 36.793, and 89.029 mg/kg, respectively. Mean
      concentrations of Cd, Pb, Sb, Mn, and As in brown rice were 0.103, 0.131, 5.175,
      6.007, and 0.524 mg/kg, respectively. Daily intakes of Cd, As, Sb, Pb, and Mn
      through brown rice consumption were estimated to be 0.011, 0.0002, 0.004, 0.0001,
      and 0.0003 mg/(kg/day), respectively. The combined hazard index for the five
      heavy metals was 22.5917, and the total cancer risk was 0.1773. Cd contributed
      most significantly to cancer risk, accounting for approximately 99.77% of this
      risk. CONCLUSIONS: The results show that potential noncarcinogenic and
      carcinogenic health risks exist for local inhabitants and that regular monitoring
      of pollution to protect human health is urgently required.

PMID- 29065601
TI  - Development of a Prototype Robotic System for Radiosurgery with Upper
      Hemispherical Workspace.
AB  - This paper introduces a specialized robotic system under development for
      radiosurgery using a small-sized linear accelerator. The robotic system is a 5
      DOF manipulator that can be installed above a patient to make an upper
      hemispherical workspace centered in a target point. In order to determine the
      optimal lengths of the link, we consider the requirements for the workspace of a
      linear accelerator for radiosurgery. A more suitable kinematic structure than
      conventional industrial manipulators is proposed, and the kinematic analysis is
      also provided. A graphic simulator is implemented and used for dynamic analysis.
      Based on those results, a prototype manipulator and its control system are under
      development.

PMID- 29065600
TI  - Model of Murine Ventricular Cardiac Tissue for In Vitro Kinematic-Dynamic Studies
      of Electromagnetic and beta-Adrenergic Stimulation.
AB  - In a model of murine ventricular cardiac tissue in vitro, we have studied the
      inotropic effects of electromagnetic stimulation (frequency, 75 Hz),
      isoproterenol administration (10 MUM), and their combination. In particular, we
      have performed an image processing analysis to evaluate the kinematics and the
      dynamics of beating cardiac syncytia starting from the video registration of
      their contraction movement. We have found that the electromagnetic stimulation is
      able to counteract the beta-adrenergic effect of isoproterenol and to elicit an
      antihypertrophic response.

PMID- 29065602
TI  - Graph-Based Semantic Web Service Composition for Healthcare Data Integration.
AB  - Within the numerous and heterogeneous web services offered through different
      sources, automatic web services composition is the most convenient method for
      building complex business processes that permit invocation of multiple existing
      atomic services. The current solutions in functional web services composition
      lack autonomous queries of semantic matches within the parameters of web
      services, which are necessary in the composition of large-scale related services.
      In this paper, we propose a graph-based Semantic Web Services composition system
      consisting of two subsystems: management time and run time. The management-time
      subsystem is responsible for dependency graph preparation in which a dependency
      graph of related services is generated automatically according to the proposed
      semantic matchmaking rules. The run-time subsystem is responsible for discovering
      the potential web services and nonredundant web services composition of a user's
      query using a graph-based searching algorithm. The proposed approach was applied
      to healthcare data integration in different health organizations and was
      evaluated according to two aspects: execution time measurement and correctness
      measurement.

PMID- 29065603
TI  - Safety of the Transcranial Focal Electrical Stimulation via Tripolar Concentric
      Ring Electrodes for Hippocampal CA3 Subregion Neurons in Rats.
AB  - Epilepsy is a neurological disorder that affects approximately one percent of the
      world population. Noninvasive electrical brain stimulation via tripolar
      concentric ring electrodes has been proposed as an alternative/complementary
      therapy for seizure control. Previous results suggest its efficacy attenuating
      acute seizures in penicillin, pilocarpine-induced status epilepticus, and
      pentylenetetrazole-induced rat seizure models and its safety for the rat scalp,
      cortical integrity, and memory formation. In this study, neuronal counting was
      used to assess possible tissue damage in rats (n = 36) due to the single dose or
      five doses (given every 24 hours) of stimulation on hippocampal CA3 subregion
      neurons 24 hours, one week, and one month after the last stimulation dose. Full
      factorial analysis of variance showed no statistically significant difference in
      the number of neurons between control and stimulation-treated animals (p = 0.71).
      Moreover, it showed no statistically significant differences due to the number of
      stimulation doses (p = 0.71) nor due to the delay after the last stimulation dose
      (p = 0.96). Obtained results suggest that stimulation at current parameters (50
      mA, 200 MUs, 300 Hz, biphasic, charge-balanced pulses for 2 minutes) does not
      induce neuronal damage in the hippocampal CA3 subregion of the brain.

PMID- 29065605
TI  - Feature Extraction and Classification on Esophageal X-Ray Images of Xinjiang
      Kazak Nationality.
AB  - Esophageal cancer is one of the fastest rising types of cancers in China. The
      Kazak nationality is the highest-risk group in Xinjiang. In this work, an
      effective computer-aided diagnostic system is developed to assist physicians in
      interpreting digital X-ray image features and improving the quality of diagnosis.
      The modules of the proposed system include image preprocessing, feature
      extraction, feature selection, image classification, and performance evaluation.
      300 original esophageal X-ray images were resized to a region of interest and
      then enhanced by the median filter and histogram equalization method. 37 features
      from textural, frequency, and complexity domains were extracted. Both sequential
      forward selection and principal component analysis methods were employed to
      select the discriminative features for classification. Then, support vector
      machine and K-nearest neighbors were applied to classify the esophageal cancer
      images with respect to their specific types. The classification performance was
      evaluated in terms of the area under the receiver operating characteristic curve,
      accuracy, precision, and recall, respectively. Experimental results show that the
      classification performance of the proposed system outperforms the conventional
      visual inspection approaches in terms of diagnostic quality and processing time.
      Therefore, the proposed computer-aided diagnostic system is promising for the
      diagnostics of esophageal cancer.

PMID- 29065606
TI  - Longitudinal Changes in Retinal Nerve Fiber Layer Thickness Evaluated Using
      Avanti Rtvue-XR Optical Coherence Tomography after 23G Vitrectomy for Epiretinal
      Membrane in Patients with Open-Angle Glaucoma.
AB  - OBJECTIVES: The aim of this study is to evaluate longitudinal RNFL thickness
      changes in patients with open-angle glaucoma (OAG) who underwent pars plana
      vitrectomy (PPV) with epiretinal membrane (ERM) and ILM removal using OCT RTVue
      XR 100 Avanti. METHODS: Retrospective analysis of OCT scans of 40 patients who
      underwent PPV or combined phacovitrectomy with ILM peeling for the idiopathic ERM
      has been carried out. The patients were divided into two groups for the study:
      patients with the ERM and OAG and those with ERM without glaucoma. A trend
      analysis of the RNFL thickness changes in 1 month and 3, 6, and 12 months was
      created. RESULTS: At 1 month after surgery, the RNFL thickness increased
      significantly in the temporalis quadrant from 89.9 MUm to 105.7 MUm in patients
      with OAG. Comparison between group with OAG and group without glaucoma showed
      that the RNFLT in the temporalis quadrant decreased significantly 6 months after
      the surgery. CONCLUSION: Postoperative changes in RNFL thickness appeared to be
      transient, and there was temporal retardation of the retinal nerve fibers without
      affecting visual acuity in both groups.

PMID- 29065607
TI  - Impact of Acetic Acid on the Survival of L. plantarum upon Microencapsulation by
      Coaxial Electrospraying.
AB  - In this work, coaxial electrospraying was used for the first time to
      microencapsulate probiotic bacteria, specifically Lactobacillus plantarum, within
      edible protein particles with the aim of improving their resistance to in vitro
      digestion. The developed structures, based on an inner core of whey protein
      concentrate and an outer layer of gelatin, were obtained in the presence of
      acetic acid in the outer solution as a requirement for the electrospraying of
      gelatin. Despite the limited contact of the inner suspension and outer solution
      during electrospraying, the combination of the high voltage used during
      electrospraying with the presence of acetic acid was found to have a severe
      impact on the lactobacilli, not only decreasing initial viability but also
      negatively affecting the survival of the bacteria during storage and their
      resistance to different stress conditions, including simulated in vitro
      digestion.

PMID- 29065604
TI  - Recent Development of Augmented Reality in Surgery: A Review.
AB  - INTRODUCTION: The development augmented reality devices allow physicians to
      incorporate data visualization into diagnostic and treatment procedures to
      improve work efficiency, safety, and cost and to enhance surgical training.
      However, the awareness of possibilities of augmented reality is generally low.
      This review evaluates whether augmented reality can presently improve the results
      of surgical procedures. METHODS: We performed a review of available literature
      dating from 2010 to November 2016 by searching PubMed and Scopus using the terms
      "augmented reality" and "surgery." Results. The initial search yielded 808
      studies. After removing duplicates and including only journal articles, a total
      of 417 studies were identified. By reading of abstracts, 91 relevant studies were
      chosen to be included. 11 references were gathered by cross-referencing. A total
      of 102 studies were included in this review. CONCLUSIONS: The present literature
      suggest an increasing interest of surgeons regarding employing augmented reality
      into surgery leading to improved safety and efficacy of surgical procedures. Many
      studies showed that the performance of newly devised augmented reality systems is
      comparable to traditional techniques. However, several problems need to be
      addressed before augmented reality is implemented into the routine practice.

PMID- 29065608
TI  - Realization of a CORDIC-Based Plug-In Accelerometer Module for PSG System in Head
      Position Monitoring for OSAS Patients.
AB  - Overnight polysomnography (PSG) is currently the standard diagnostic procedure
      for obstructive sleep apnea (OSA). It has been known that monitoring of head
      position in sleep is crucial not only for the diagnosis (positional sleep apnea)
      but also for the management of OSA (positional therapy). However, there are no
      sensor systems available clinically to hook up with PSG for accurate head
      position monitoring. In this paper, an accelerometer-based sensing system for
      accurate head position monitoring is developed and realized. The core CORDIC-
      (COordinate Rotation DIgital Computer-) based tilting sensing algorithm is
      realized in the system to quickly and accurately convert accelerometer raw data
      into the desired head position tilting angles. The system can hook up with PSG
      devices for diagnosis to have head position information integrated with other PSG
      monitored signals. It has been applied in an IRB test in Taipei Veterans General
      Hospital and has been proved that it can meet the medical needs of accurate head
      position monitoring for PSG diagnosis.

PMID- 29065609
TI  - Molecular Skin Surface-Based Transformation Visualization between Biological
      Macromolecules.
AB  - Molecular skin surface (MSS), proposed by Edelsbrunner, is a C2 continuous smooth
      surface modeling approach of biological macromolecules. Compared to the
      traditional methods of molecular surface representations (e.g., the solvent
      exclusive surface), MSS has distinctive advantages including having no self
      intersection and being decomposable and transformable. For further promoting MSS
      to the field of bioinformatics, transformation between different MSS
      representations mimicking the macromolecular dynamics is demanded. The
      transformation process helps biologists understand the macromolecular dynamics
      processes visually in the atomic level, which is important in studying the
      protein structures and binding sites for optimizing drug design. However,
      modeling the transformation between different MSSs suffers from high
      computational cost while the traditional approaches reconstruct every
      intermediate MSS from respective intermediate union of balls. In this study, we
      propose a novel computational framework named general MSS transformation
      framework (GMSSTF) between two MSSs without the assistance of union of balls. To
      evaluate the effectiveness of GMSSTF, we applied it on a popular public database
      PDB (Protein Data Bank) and compared the existing MSS algorithms with and without
      GMSSTF. The simulation results show that the proposed GMSSTF effectively improves
      the computational efficiency and is potentially useful for macromolecular dynamic
      simulations.

PMID- 29065610
TI  - Hollow Abutment Screw Design for Easy Retrieval in Case of Screw Fracture in
      Dental Implant System.
AB  - The prosthetic component of dental implant is attached on the abutment which is
      connected to the fixture with an abutment screw. The abutment screw fracture is
      not frequent; however, the retrieval of the fractured screw is not easy, and it
      poses complications. A retrieval kit was developed which utilizes screw removal
      drills to make a hole on the fractured screw that provides an engaging drill to
      unscrew it. To minimize this process, the abutment screw is modified with a
      prefabricated access hole for easy retrieval. This study aimed to introduce this
      modified design of the abutment screw, the concept of easy retrieval, and to
      compare the mechanical strengths of the conventional and hollow abutment screws
      by finite element analysis (FEA) and mechanical test. In the FEA results, both
      types of abutment screws showed similar stress distribution in the single
      artificial tooth system. A maximum load difference of about 2% occurred in the
      vertical load by a mechanical test. This study showed that the hollow abutment
      screw may be an alternative to the conventional abutment screws because this is
      designed for easy retrieval and that both abutment screws showed no significant
      difference in the mechanical tests and in the FEA.

PMID- 29065611
TI  - Blood Vessel Extraction in Color Retinal Fundus Images with Enhancement Filtering
      and Unsupervised Classification.
AB  - Retinal blood vessels have a significant role in the diagnosis and treatment of
      various retinal diseases such as diabetic retinopathy, glaucoma,
      arteriosclerosis, and hypertension. For this reason, retinal vasculature
      extraction is important in order to help specialists for the diagnosis and
      treatment of systematic diseases. In this paper, a novel approach is developed to
      extract retinal blood vessel network. Our method comprises four stages: (1)
      preprocessing stage in order to prepare dataset for segmentation; (2) an
      enhancement procedure including Gabor, Frangi, and Gauss filters obtained
      separately before a top-hat transform; (3) a hard and soft clustering stage which
      includes K-means and Fuzzy C-means (FCM) in order to get binary vessel map; and
      (4) a postprocessing step which removes falsely segmented isolated regions. The
      method is tested on color retinal images obtained from STARE and DRIVE databases
      which are available online. As a result, Gabor filter followed by K-means
      clustering method achieves 95.94% and 95.71% of accuracy for STARE and DRIVE
      databases, respectively, which are acceptable for diagnosis systems.

PMID- 29065613
TI  - R Peak Detection Method Using Wavelet Transform and Modified Shannon Energy
      Envelope.
AB  - Rapid automatic detection of the fiducial points-namely, the P wave, QRS complex,
      and T wave-is necessary for early detection of cardiovascular diseases (CVDs). In
      this paper, we present an R peak detection method using the wavelet transform
      (WT) and a modified Shannon energy envelope (SEE) for rapid ECG analysis. The
      proposed WTSEE algorithm performs a wavelet transform to reduce the size and
      noise of ECG signals and creates SEE after first-order differentiation and
      amplitude normalization. Subsequently, the peak energy envelope (PEE) is
      extracted from the SEE. Then, R peaks are estimated from the PEE, and the
      estimated peaks are adjusted from the input ECG. Finally, the algorithm generates
      the final R features by validating R-R intervals and updating the extracted R
      peaks. The proposed R peak detection method was validated using 48 first-channel
      ECG records of the MIT-BIH arrhythmia database with a sensitivity of 99.93%,
      positive predictability of 99.91%, detection error rate of 0.16%, and accuracy of
      99.84%. Considering the high detection accuracy and fast processing speed due to
      the wavelet transform applied before calculating SEE, the proposed method is
      highly effective for real-time applications in early detection of CVDs.

PMID- 29065612
TI  - A Novel Approach towards Medical Entity Recognition in Chinese Clinical Text.
AB  - Medical entity recognition, a basic task in the language processing of clinical
      data, has been extensively studied in analyzing admission notes in alphabetic
      languages such as English. However, much less work has been done on nonstructural
      texts that are written in Chinese, or in the setting of differentiation of
      Chinese drug names between traditional Chinese medicine and Western medicine.
      Here, we propose a novel cascade-type Chinese medication entity recognition
      approach that aims at integrating the sentence category classifier from a support
      vector machine and the conditional random field-based medication entity
      recognition. We hypothesized that this approach could avoid the side effects of
      abundant negative samples and improve the performance of the named entity
      recognition from admission notes written in Chinese. Therefore, we applied this
      approach to a test set of 324 Chinese-written admission notes with manual
      annotation by medical experts. Our data demonstrated that this approach had a
      score of 94.2% in precision, 92.8% in recall, and 93.5% in F-measure for the
      recognition of traditional Chinese medicine drug names and 91.2% in precision,
      92.6% in recall, and 91.7% F-measure for the recognition of Western medicine drug
      names. The differences in F-measure were significant compared with those in the
      baseline systems.

PMID- 29065614
TI  - Development and Implementation of an End-Effector Upper Limb Rehabilitation Robot
      for Hemiplegic Patients with Line and Circle Tracking Training.
AB  - Numerous robots have been widely used to deliver rehabilitative training for
      hemiplegic patients to improve their functional ability. Because of the
      complexity and diversity of upper limb motion, customization of training patterns
      is one key factor during upper limb rehabilitation training. Most of the current
      rehabilitation robots cannot intelligently provide adaptive training parameters,
      and they have not been widely used in clinical rehabilitation. This article
      proposes a new end-effector upper limb rehabilitation robot, which is a two-link
      robotic arm with two active degrees of freedom. This work investigated the
      kinematics and dynamics of the robot system, the control system, and the
      realization of different rehabilitation therapies. We also explored the influence
      of constraint in rehabilitation therapies on interaction force and muscle
      activation. The deviation of the trajectory of the end effector and the required
      trajectory was less than 1 mm during the tasks, which demonstrated the movement
      accuracy of the robot. Besides, results also demonstrated the constraint exerted
      by the robot provided benefits for hemiplegic patients by changing muscle
      activation in the way similar to the movement pattern of the healthy subjects,
      which indicated that the robot can improve the patient's functional ability by
      training the normal movement pattern.

PMID- 29065615
TI  - Effects of Pectus Excavatum on the Spine of Pectus Excavatum Patients with
      Scoliosis.
AB  - BACKGROUND: There is high risk in the correction surgery of pectus excavatum with
      scoliosis because of the lack of the correction mechanism of pectus excavatum
      with scoliosis. This study performed a comprehensive analysis about the impact
      that pectus excavatum had on scoliosis and elaborated its biomechanical mechanism
      in pectus excavatum patients with scoliosis. METHODS: 37 pectus excavatum
      patients were selected. According to age, Haller index of pectus excavatum,
      offset coefficient, vertical position, sternal torsion angle, and asymmetric
      index, 37 patients were, respectively, divided into 2 compared groups. The result
      was statistically calculated. RESULTS: The scoliosis incidence and severity did
      not correlate with Haller index, offset coefficient, vertical position, sternal
      torsion angle, and asymmetric index of pectus excavatum, and there was no
      statistical significance between the two compared groups. CONCLUSIONS: The
      incidence and severity of scoliosis in PE patients with scoliosis have nothing to
      do with the geometric parameters of pectus excavatum but correlate with age. The
      scoliosis will aggravate with the increase of age. The heart may provide an
      asymmetric horizontal force to push the spines to the right. The mechanism of how
      the biomechanical factors exert influences on spines needs to be further
      investigated to keep the spine stable.

PMID- 29065616
TI  - Smartphone-Driven Low-Power Light-Emitting Device.
AB  - Low-level light (laser) therapy (LLLT) has been widely researched in the recent
      past. Existing LLLT studies were performed based on laser. Recently, studies
      using LED have increased. This study presents a smartphone-driven low-power light
      emitting device for use in colour therapy as an alternative medicine. The device
      consists of a control unit and a colour probe. The device is powered by and
      communicates with a smartphone using USB On-The-Go (OTG) technology. The control
      unit controls emitting time and intensity of illumination with the configuration
      value of a smartphone application. Intensity is controlled by pulse width
      modulation (PWM) without feedback. A calibration is performed to resolve a
      drawback of no feedback. To calibrate, intensity is measured in every 10 percent
      PWM output. PWM value is linearly calibrated to obtain accurate intensity. The
      device can control the intensity of illumination, and so, it can find application
      in varied scenarios.

PMID- 29065617
TI  - Incorporating Topic Assignment Constraint and Topic Correlation Limitation into
      Clinical Goal Discovering for Clinical Pathway Mining.
AB  - Clinical pathways are widely used around the world for providing quality medical
      treatment and controlling healthcare cost. However, the expert-designed clinical
      pathways can hardly deal with the variances among hospitals and patients. It
      calls for more dynamic and adaptive process, which is derived from various
      clinical data. Topic-based clinical pathway mining is an effective approach to
      discover a concise process model. Through this approach, the latent topics found
      by latent Dirichlet allocation (LDA) represent the clinical goals. And process
      mining methods are used to extract the temporal relations between these topics.
      However, the topic quality is usually not desirable due to the low performance of
      the LDA in clinical data. In this paper, we incorporate topic assignment
      constraint and topic correlation limitation into the LDA to enhance the ability
      of discovering high-quality topics. Two real-world datasets are used to evaluate
      the proposed method. The results show that the topics discovered by our method
      are with higher coherence, informativeness, and coverage than the original LDA.
      These quality topics are suitable to represent the clinical goals. Also, we
      illustrate that our method is effective in generating a comprehensive topic-based
      clinical pathway model.

PMID- 29065618
TI  - Removal of Arterial Vessel Contributions in Susceptibility-Weighted Images for
      Quantification of Normalized Visible Venous Volume in Children with Sickle Cell
      Disease.
AB  - PURPOSE: To evaluate a new postprocessing framework that eliminates arterial
      vessel signal contributions in the quantification of normalized visible venous
      volume (NVVV, a ratio between venous and brain volume) in susceptibility-weighted
      imaging (SWI) exams in patients with sickle cell disease (SCD). MATERIALS AND
      METHODS: We conducted a retrospective study and qualitatively reviewed for
      hypointense arterial vessel contamination in SWI exams from 21 children with SCD.
      We developed a postprocessing framework using magnetic resonance angiography in
      combination with SWI to provide a more accurate quantification of NVVV. NVVV was
      calculated before and after removing arterial vessel contributions to determine
      the error from hypointense arterial vessels in quantifying NVVV. RESULTS:
      Hypointense arterial vessel contamination was observed in 86% SWI exams and was
      successfully corrected by the proposed method. The contributions of hypointense
      arterial vessels in the original SWI were significant and accounted for
      approximately 33% of the NVVV [uncorrected NVVV = 0.012 +/- 0.005 versus
      corrected NVVV = 0.008 +/- 0.003 (mean +/- SD), P < 0.01]. CONCLUSION:
      Hypointense arterial vessel contamination occurred in the majority of SWI exams
      and led to a sizeable overestimation of the visible venous volume. A prospective
      longitudinal study is needed to evaluate if quantitation of NVVV was improved and
      to assess the role of NVVV as a biomarker of SCD severity or stroke risk.

PMID- 29065619
TI  - Diagnosis of Alzheimer's Disease Based on Structural MRI Images Using a
      Regularized Extreme Learning Machine and PCA Features.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative brain disorder that
      attacks neurotransmitters, brain cells, and nerves, affecting brain functions,
      memory, and behaviors and then finally causing dementia on elderly people.
      Despite its significance, there is currently no cure for it. However, there are
      medicines available on prescription that can help delay the progress of the
      condition. Thus, early diagnosis of AD is essential for patient care and relevant
      researches. Major challenges in proper diagnosis of AD using existing
      classification schemes are the availability of a smaller number of training
      samples and the larger number of possible feature representations. In this paper,
      we present and compare AD diagnosis approaches using structural magnetic
      resonance (sMR) images to discriminate AD, mild cognitive impairment (MCI), and
      healthy control (HC) subjects using a support vector machine (SVM), an import
      vector machine (IVM), and a regularized extreme learning machine (RELM). The
      greedy score-based feature selection technique is employed to select important
      feature vectors. In addition, a kernel-based discriminative approach is adopted
      to deal with complex data distributions. We compare the performance of these
      classifiers for volumetric sMR image data from Alzheimer's disease neuroimaging
      initiative (ADNI) datasets. Experiments on the ADNI datasets showed that RELM
      with the feature selection approach can significantly improve classification
      accuracy of AD from MCI and HC subjects.

PMID- 29065620
TI  - An Approach to Evaluate Blurriness in Retinal Images with Vitreous Opacity for
      Cataract Diagnosis.
AB  - Cataract is one of the leading causes of blindness in the world's population. A
      method to evaluate blurriness for cataract diagnosis in retinal images with
      vitreous opacity is proposed in this paper. Three types of features are
      extracted, which include pixel number of visible structures, mean contrast
      between vessels and background, and local standard deviation. To avoid the wrong
      detection of vitreous opacity as retinal structures, a morphological method is
      proposed to detect and remove such lesions from retinal visible structure
      segmentation. Based on the extracted features, a decision tree is trained to
      classify retinal images into five grades of blurriness. The proposed approach was
      tested using 1355 clinical retinal images, and the accuracies of two-class
      classification and five-grade grading compared with that of manual grading are
      92.8% and 81.1%, respectively. The kappa value between automatic grading and
      manual grading is 0.74 in five-grade grading, in which both variance and P value
      are less than 0.001. Experimental results show that the grading difference
      between automatic grading and manual grading is all within 1 grade, which is much
      improvement compared with that of other available methods. The proposed grading
      method provides a universal measure of cataract severity and can facilitate the
      decision of cataract surgery.

PMID- 29065621
TI  - Comparison of Morphologic Parameters of Temporomandibular Joint for Asymptomatic
      Subjects Using the Two-Dimensional and Three-Dimensional Measuring Methods.
AB  - The differences of temporomandibular joint (TMJ) morphologic parameters by using
      two-dimensional (2D) and three-dimensional (3D) measuring methods were compared.
      Ten asymptomatic subjects (26.75 +/- 4.89 years) were randomly recruited. The 3D
      models of the maxilla, mandible, and teeth were reconstructed according to cone
      beam computed tomography (CBCT) image data. The morphologic parameters of TMJs
      were measured by the 2D CBCT measuring method (group A) and the 3D reconstruction
      model measuring method (group B), respectively. The morphologic parameters in
      each group were assessed by paired samples t-test, and the statistical
      significance was achieved when p < 0.05. The horizontal condylar angle (HCA),
      sagittal ramus angle (SRA), medial joint space (MJS), lateral joint space (LJS),
      superior joint space (SJS), and anterior joint space (AJS) in group A were
      significantly smaller than those in group B (p < 0.05). The HCA on the left side
      was significantly smaller than that on the right side in group A (p < 0.05).
      However, all the morphologic parameters in group B were not significantly
      different between left and right sides. In conclusion, there were significant
      differences for the morphologic parameters of TMJ measured on 2D CBCT and 3D
      models. 3D measuring method should be used for the detection of TMJ morphology in
      clinical practice.

PMID- 29065622
TI  - Effects of Two Fatigue Protocols on Impact Forces and Lower Extremity Kinematics
      during Drop Landings: Implications for Noncontact Anterior Cruciate Ligament
      Injury.
AB  - The purpose of the study was to determine the effects of fatigue on the impact
      forces and sagittal plane kinematics of the lower extremities in a drop landing
      task. 15 male collegiate athletes were recruited. Five successful trials of a
      drop landing task were obtained during prefatigue and postfatigue in two fatigue
      protocols (constant speed running fatigue protocol [R-FP] and shuttle running +
      vertical jumping fatigue protocol [SV-FP]). Duration time, maximal heart rate,
      and RPE of each protocol were measured separately. Kinematic measures of the hip,
      knee, and ankle joints at different times coupled with peak impact force and
      loading rate were acquired. Our results showed a more flexed landing posture due
      to an increase in hip and knee flexion angles in the postfatigue condition.
      However, no differences in peak impact force and loading rate were found between
      pre- and postfatigue conditions. The changes were similar between protocols, but
      the SV-FP showed a significantly shorter exercise duration time than the R-FP.
      Fatigued athletes in this study demonstrated altered motor control strategies
      during a drop landing task, which may be an intentional or unintentional
      protective strategy for preventing themselves from potential ACL injury.

PMID- 29065623
TI  - Segmentation Method for Magnetic Resonance-Guided High-Intensity Focused
      Ultrasound Therapy Planning.
AB  - High-intensity focused ultrasound (HIFU) is a minimally invasive therapy modality
      in which ultrasound beams are concentrated at a focal region, producing a rise of
      temperature and selective ablation within the focal volume and leaving
      surrounding tissues intact. HIFU has been proposed for the safe ablation of both
      malignant and benign tissues and as an agent for drug delivery. Magnetic
      resonance imaging (MRI) has been proposed as guidance and monitoring method for
      the therapy. The identification of regions of interest is a crucial procedure in
      HIFU therapy planning. This procedure is performed in the MR images. The purpose
      of the present research work is to implement a time-efficient and functional
      segmentation scheme, based on the watershed segmentation algorithm, for the MR
      images used for the HIFU therapy planning. The achievement of a segmentation
      process with functional results is feasible, but preliminary image processing
      steps are required in order to define the markers for the segmentation algorithm.
      Moreover, the segmentation scheme is applied in parallel to an MR image data set
      through the use of a thread pool, achieving a near real-time execution and making
      a contribution to solve the time-consuming problem of the HIFU therapy planning.

PMID- 29065625
TI  - Deep Learning- and Transfer Learning-Based Super Resolution Reconstruction from
      Single Medical Image.
AB  - Medical images play an important role in medical diagnosis and research. In this
      paper, a transfer learning- and deep learning-based super resolution
      reconstruction method is introduced. The proposed method contains one bicubic
      interpolation template layer and two convolutional layers. The bicubic
      interpolation template layer is prefixed by mathematics deduction, and two
      convolutional layers learn from training samples. For saving training medical
      images, a SIFT feature-based transfer learning method is proposed. Not only can
      medical images be used to train the proposed method, but also other types of
      images can be added into training dataset selectively. In empirical experiments,
      results of eight distinctive medical images show improvement of image quality and
      time reduction. Further, the proposed method also produces slightly sharper edges
      than other deep learning approaches in less time and it is projected that the
      hybrid architecture of prefixed template layer and unfixed hidden layers has
      potentials in other applications.

PMID- 29065624
TI  - Effects of Scan Resolutions and Element Sizes on Bovine Vertebral Mechanical
      Parameters from Quantitative Computed Tomography-Based Finite Element Analysis.
AB  - Quantitative computed tomography-based finite element analysis (QCT/FEA) has been
      developed to predict vertebral strength. However, QCT/FEA models may be different
      with scan resolutions and element sizes. The aim of this study was to explore the
      effects of scan resolutions and element sizes on QCT/FEA outcomes. Nine bovine
      vertebral bodies were scanned using the clinical CT scanner and reconstructed
      from datasets with the two-slice thickness, that is, 0.6 mm (PA resolution) and 1
      mm (PB resolution). There were significantly linear correlations between the
      predicted and measured principal strains (R2 > 0.7, P < 0.0001), and the
      predicted vertebral strength and stiffness were modestly correlated with the
      experimental values (R2 > 0.6, P < 0.05). Two different resolutions and six
      different element sizes were combined in pairs, and finite element (FE) models of
      bovine vertebral cancellous bones in the 12 cases were obtained. It showed that
      the mechanical parameters of FE models with the PB resolution were similar to
      those with the PA resolution. The computational accuracy of FE models with the
      element sizes of 0.41 * 0.41 * 0.6 mm3 and 0.41 * 0.41 * 1 mm3 was higher by
      comparing the apparent elastic modulus and yield strength. Therefore, scan
      resolution and element size should be chosen optimally to improve the accuracy of
      QCT/FEA.

PMID- 29065626
TI  - Hybrid Disease Diagnosis Using Multiobjective Optimization with Evolutionary
      Parameter Optimization.
AB  - With the widespread adoption of e-Healthcare and telemedicine applications,
      accurate, intelligent disease diagnosis systems have been profoundly coveted. In
      recent years, numerous individual machine learning-based classifiers have been
      proposed and tested, and the fact that a single classifier cannot effectively
      classify and diagnose all diseases has been almost accorded with. This has seen a
      number of recent research attempts to arrive at a consensus using ensemble
      classification techniques. In this paper, a hybrid system is proposed to diagnose
      ailments using optimizing individual classifier parameters for two classifier
      techniques, namely, support vector machine (SVM) and multilayer perceptron (MLP)
      technique. We employ three recent evolutionary algorithms to optimize the
      parameters of the classifiers above, leading to six alternative hybrid disease
      diagnosis systems, also referred to as hybrid intelligent systems (HISs).
      Multiple objectives, namely, prediction accuracy, sensitivity, and specificity,
      have been considered to assess the efficacy of the proposed hybrid systems with
      existing ones. The proposed model is evaluated on 11 benchmark datasets, and the
      obtained results demonstrate that our proposed hybrid diagnosis systems perform
      better in terms of disease prediction accuracy, sensitivity, and specificity.
      Pertinent statistical tests were carried out to substantiate the efficacy of the
      obtained results.

PMID- 29065627
TI  - Effect of Color Light Stimulation Using LED on Sleep Induction Time.
AB  - The effects of color are already being used widely. For this reason, in this
      study, an attempt was made to use such effects of color to examine the changes in
      sleep onset through the use of the preferred and nonpreferred color light
      stimulation. Color light stimulations were randomly presented to the subjects,
      and based on these colors, the changes in sleep onset were examined through the
      EEG. Also, to quantify the physiological changes that were caused by each color
      light stimulation, the changes in the HRV were examined through ECG to determine
      the level of activation of the autonomous nervous system. The results showed that
      sleep onset time was changed based on the light stimulation. The result of the
      EEG analysis showed that sleep onset time was most significantly shortened in
      preferred color light stimulation. Also, the result of HRV was the fastest change
      about both the time domain and the frequency domain in the preferred color light
      stimulation. Therefore, because the preferred color light stimulation activated
      the parasympathetic nervous system, sleep was induced quickly. Also, by simply
      using the HRV, the differences in the index of HRV showed changes of sleep onset
      according to the color light stimulation.

PMID- 29065628
TI  - The Effect of Lumbar Disc Herniation on Spine Loading Characteristics during
      Trunk Flexion and Two Types of Picking Up Activities.
AB  - The main purpose of this study was to investigate the compensatory response of
      the muscle activities of seventeen major muscle groups in the spinal region,
      intradiscal forces of the five lumbar motion segment units (MSUs), and facet
      forces acting on the ten lumbar facet joints in patients with lumbar disc
      herniation (LDH). Twenty-six healthy adults and seven LDH patients performed
      trunk flexion, ipsilateral picking up, and contralateral picking up in sequence.
      Eight optical markers were placed on the landmarks of the pelvis and spinal
      process. The coordinates of these markers were captured to drive a
      musculoskeletal model to calculate the muscle activities, intradiscal forces, and
      facet forces. The muscle activities of the majority of the seventeen major muscle
      groups were found increases in LDH patients. In addition, the LDH patients
      displayed larger compressive forces and anteroposterior forces on all the five
      lumbar MSUs and more lumbar facet inventions on most facet joints. These findings
      suggest that the LDH patients demonstrate compensatory increases in the most
      trunk muscle activities and all spinal loads. These negative compensatory
      responses increase the risk of the aggravation of disc herniation. Therefore,
      treatment should intervene as earlier as possible for the severe LDH patients.

PMID- 29065629
TI  - Exploring Space Management Goals in Institutional Care Facilities in China.
AB  - Space management has been widely examined in commercial facilities, educational
      facilities, and hospitals but not in China's institutional care facilities. Poor
      spatial arrangements, such as wasted space, dysfunctionality, and environment
      mismanagement, are increasing; in turn, the occupancy rate is decreasing due to
      residential dissatisfaction. To address these problems, this paper's objective is
      to explore the space management goals (SMGs) in institutional care facilities in
      China. Systematic literature analysis was adopted to set SMGs' principles, to
      identify nine theoretical SMGs, and to develop the conceptual model of SMGs for
      institutional care facilities. A total of 19 intensive interviews were conducted
      with stakeholders in seven institutional care facilities to collect data for
      qualitative analysis. The qualitative evidence was analyzed through open coding,
      axial coding, and selective coding. As a result, six major categories as well as
      their interrelationships were put forward to visualize the path diagram for
      exploring SMGs in China's institutional care facilities. Furthermore, seven
      expected SMGs that were explored from qualitative evidence were confirmed as
      China's SMGs in institutional care facilities by a validation test. Finally, a
      gap analysis among theoretical SMGs and China's SMGs provided recommendations for
      implementing space management in China's institutional care facilities.

PMID- 29065630
TI  - Influence of Gait Speeds on Contact Forces of Lower Limbs.
AB  - While walking with fast speed aims to promote health and fitness of individuals,
      the potential risk on lower limb joint loading across walking speed is still
      unknown. In order to determine the joint contact force loading associated with
      different walking speeds, fifteen young male and fifteen female participants
      performed barefoot walking across different speeds (regular = 1.1 m/s, medium =
      1.4 m/s, and fast = 1.7 m/s). The synchronized motion and ground reaction force
      (GRF) data were captured by Codamotion capture system and AMTI force platform.
      All kinematics and GRF information were input to the AnyBody musculoskeletal
      model to determine 3-dimensional knee contact forces. The results showed that
      increased walking speed was associated with a greater proximal-distal and
      anterior-posterior GRF during early impact phase, implying that the joint
      stability is more demanding at higher walking speed conditions (P < 0.05). In
      addition, higher proximal-distal and anterior-posterior knee contact forces were
      found when participants were walking at higher speeds (P < 0.05). Therefore, the
      risk of knee cartilage and ligament damage associated with the increased knee
      contact forces should require further attention.

PMID- 29065631
TI  - Association Patterns of Ontological Features Signify Electronic Health Records in
      Liver Cancer.
AB  - Electronic Health Record (EHR) system enables clinical decision support. In this
      study, a set of 112 abdominal computed tomography imaging examination reports,
      consisting of 59 cases of hepatocellular carcinoma (HCC) or liver metastases (so
      called HCC group for simplicity) and 53 cases with no abnormality detected (NAD
      group), were collected from four hospitals in Hong Kong. We extracted terms
      related to liver cancer from the reports and mapped them to ontological features
      using Systematized Nomenclature of Medicine (SNOMED) Clinical Terms (CT). The
      primary predictor panel was formed by these ontological features. Association
      levels between every two features in the HCC and NAD groups were quantified using
      Pearson's correlation coefficient. The HCC group reveals a distinct association
      pattern that signifies liver cancer and provides clinical decision support for
      suspected cases, motivating the inclusion of new features to form the augmented
      predictor panel. Logistic regression analysis with stepwise forward procedure was
      applied to the primary and augmented predictor sets, respectively. The obtained
      model with the new features attained 84.7% sensitivity and 88.4% overall accuracy
      in distinguishing HCC from NAD cases, which were significantly improved when
      compared with that without the new features.

PMID- 29065632
TI  - Anti-Skin Cancer Activities of Apostichopus japonicus Extracts from Low
      Temperature Ultrasonification Process.
AB  - OBJECTIVES: This work aimed to enhance anti-skin cancer activities of
      Apostichopus japonicus, spiky sea cucumber, through ultrasonification extraction
      process at low temperature. METHODS: Dried Apostichopus japonicus was extracted
      with an ultrasonification process at 50 degrees C and 95 kHz for two hours (UE),
      and anti-skin cancer activities of the extract from the UE were also compared
      with those from conventional extraction processes using hot water (WE) or 70%
      ethanol at 80 degrees C (EE) for 12 hours. RESULTS: The amount of canthaxanthin
      in the UE was higher than that in the WE or EE, and its cytotoxicity against
      human keratinocytes was less than the others. The extract from the UE showed
      93.5% inhibition against human malignant cell growth, which was also higher than
      those from both WE and EE. The extract from the UE demonstrated the ability of
      inhibiting both cancer cell proliferation and metastasis by downregulating the
      skin tumor-promoting genes such as Bcl-2, STAT3, and MMP-9. CONCLUSIONS: The
      ultrasonification process was proved to be effective especially in extracting
      heat-sensitive marine biomass, A. japonicus having higher amounts of
      canthaxanthin and better anti-skin cancer activities, possibly due to less
      destruction and high elution of bioactive substances under low temperature
      extraction condition.

PMID- 29065633
TI  - The Research of Clinical Decision Support System Based on Three-Layer Knowledge
      Base Model.
AB  - In many clinical decision support systems, a two-layer knowledge base model
      (disease-symptom) of rule reasoning is used. This model often does not express
      knowledge very well since it simply infers disease from the presence of certain
      symptoms. In this study, we propose a three-layer knowledge base model (disease
      symptom-property) to utilize more useful information in inference. The system
      iteratively calculates the probability of patients who may suffer from diseases
      based on a multisymptom naive Bayes algorithm, in which the specificity of these
      disease symptoms is weighted by the estimation of the degree of contribution to
      diagnose the disease. It significantly reduces the dependencies between
      attributes to apply the naive Bayes algorithm more properly. Then, the online
      learning process for parameter optimization of the inference engine was
      completed. At last, our decision support system utilizing the three-layer model
      was formally evaluated by two experienced doctors. By comparisons between
      prediction results and clinical results, our system can provide effective
      clinical recommendations to doctors. Moreover, we found that the three-layer
      model can improve the accuracy of predictions compared with the two-layer model.
      In light of some of the limitations of this study, we also identify and discuss
      several areas that need continued improvement.

PMID- 29065634
TI  - A Queue-Based Monte Carlo Analysis to Support Decision Making for Implementation
      of an Emergency Department Fast Track.
AB  - Emergency departments (EDs) are seeking ways to utilize existing resources more
      efficiently as they face rising numbers of patient visits. This study explored
      the impact on patient wait times and nursing resource demand from the addition of
      a fast track, or separate unit for low-acuity patients, in the ED using a queue
      based Monte Carlo simulation in MATLAB. The model integrated principles of
      queueing theory and expanded the discrete event simulation to account for time
      based arrival rates. Additionally, the ED occupancy and nursing resource demand
      were modeled and analyzed using the Emergency Severity Index (ESI) levels of
      patients, rather than the number of beds in the department. Simulation results
      indicated that the addition of a separate fast track with an additional nurse
      reduced overall median wait times by 35.8 +/- 2.2 percent and reduced average
      nursing resource demand in the main ED during hours of operation. This novel
      modeling approach may be easily disseminated and informs hospital decision-makers
      of the impact of implementing a fast track or similar system on both patient wait
      times and acuity-based nursing resource demand.

PMID- 29065635
TI  - Surgeon Training in Telerobotic Surgery via a Hardware-in-the-Loop Simulator.
AB  - This work presents a software and hardware framework for a telerobotic surgery
      safety and motor skill training simulator. The aims are at providing trainees a
      comprehensive simulator for acquiring essential skills to perform telerobotic
      surgery. Existing commercial robotic surgery simulators lack features for safety
      training and optimal motion planning, which are critical factors in ensuring
      patient safety and efficiency in operation. In this work, we propose a hardware
      in-the-loop simulator directly introducing these two features. The proposed
      simulator is built upon the Raven-IITM open source surgical robot, integrated
      with a physics engine and a safety hazard injection engine. Also, a Fast Marching
      Tree-based motion planning algorithm is used to help trainee learn the optimal
      instrument motion patterns. The main contributions of this work are (1)
      reproducing safety hazards events, related to da VinciTM system, reported to the
      FDA MAUDE database, with a novel haptic feedback strategy to provide feedback to
      the operator when the underlying dynamics differ from the real robot's states so
      that the operator will be aware and can mitigate the negative impact of the
      safety-critical events, and (2) using motion planner to generate semioptimal path
      in an interactive robotic surgery training environment.

PMID- 29065636
TI  - Iterative Learning Impedance for Lower Limb Rehabilitation Robot.
AB  - This paper discusses the problem of squatting training of stroke patients. The
      main idea is to correct the patient's training trajectory through an iterative
      learning control (ILC) method. To obtain better rehabilitation effect, a patient
      will typically be required to practice a reference posture for many times, while
      most of active training methods can hardly keep the patients training with
      correct posture. Instead of the conventional ILC strategy, an impedance-based
      iterative learning method is proposed to regulate the impedance value dynamically
      and smartly which will help patients correct their posture gradually and perform
      better. To facilitate impedance-based ILC, we propose two objectives. The first
      objective is to find the suitable values of impedance based on the ILC scheme.
      The second objective is to search the moderate learning convergence speed and
      robustness in the iterative domain. The simulation and experimental results
      demonstrate that the performance of trajectory tracking will be improved greatly
      via the proposed algorithm.

PMID- 29065638
TI  - Data Mining for Biomedicine and Healthcare.

PMID- 29065637
TI  - Early Spatiotemporal Patterns and Knee Kinematics during Level Walking in
      Individuals following Total Knee Arthroplasty.
AB  - PURPOSE: With the aim of investigating the spatiotemporal features of early gait
      pattern and knee kinematics after total knee arthroplasty and analyzing the
      association between outcomes of gait analyses and knee kinematic parameters, the
      relationship between walking and dynamic knee deformity at the early period after
      total knee arthroplasty was assessed in this study. METHODS: Eighteen patients
      including 14 women and 4 men who underwent total knee arthroplasty were analyzed
      using three-dimensional gait analysis system to observe gait parameters and
      values of maximum knee flexion angle (MKFA) during swing phase and knee flexion
      angle (KFA) and knee valgus angle (KVA) at midstance phase. RESULTS: 3D gait
      analysis showed that operated side exhibited significantly less total support
      time and single support time as well as significantly longer swing phase compared
      with the other side. During walking, the operated side had significantly smaller
      MKFA and greater KFA and KVA than the nonoperated side. There was moderate to
      significant correlation between gait pattern and the dynamic knee kinematics.
      CONCLUSION: The gait abnormality of patients after TKA was associated with
      inadequate flexion of knees at swing phase and insufficient extension at stance
      phase as well as increased range of valgus.

PMID- 29065639
TI  - A Real-Time Analysis Method for Pulse Rate Variability Based on Improved Basic
      Scale Entropy.
AB  - Base scale entropy analysis (BSEA) is a nonlinear method to analyze heart rate
      variability (HRV) signal. However, the time consumption of BSEA is too long, and
      it is unknown whether the BSEA is suitable for analyzing pulse rate variability
      (PRV) signal. Therefore, we proposed a method named sliding window iterative base
      scale entropy analysis (SWIBSEA) by combining BSEA and sliding window iterative
      theory. The blood pressure signals of healthy young and old subjects are chosen
      from the authoritative international database MIT/PhysioNet/Fantasia to generate
      PRV signals as the experimental data. Then, the BSEA and the SWIBSEA are used to
      analyze the experimental data; the results show that the SWIBSEA reduces the time
      consumption and the buffer cache space while it gets the same entropy as BSEA.
      Meanwhile, the changes of base scale entropy (BSE) for healthy young and old
      subjects are the same as that of HRV signal. Therefore, the SWIBSEA can be used
      for deriving some information from long-term and short-term PRV signals in real
      time, which has the potential for dynamic PRV signal analysis in some portable
      and wearable medical devices.

PMID- 29065640
TI  - A Fast SVM-Based Tongue's Colour Classification Aided by k-Means Clustering
      Identifiers and Colour Attributes as Computer-Assisted Tool for Tongue Diagnosis.
AB  - In tongue diagnosis, colour information of tongue body has kept valuable
      information regarding the state of disease and its correlation with the internal
      organs. Qualitatively, practitioners may have difficulty in their judgement due
      to the instable lighting condition and naked eye's ability to capture the exact
      colour distribution on the tongue especially the tongue with multicolour
      substance. To overcome this ambiguity, this paper presents a two-stage tongue's
      multicolour classification based on a support vector machine (SVM) whose support
      vectors are reduced by our proposed k-means clustering identifiers and red colour
      range for precise tongue colour diagnosis. In the first stage, k-means clustering
      is used to cluster a tongue image into four clusters of image background (black),
      deep red region, red/light red region, and transitional region. In the second
      stage classification, red/light red tongue images are further classified into red
      tongue or light red tongue based on the red colour range derived in our work.
      Overall, true rate classification accuracy of the proposed two-stage
      classification to diagnose red, light red, and deep red tongue colours is 94%.
      The number of support vectors in SVM is improved by 41.2%, and the execution time
      for one image is recorded as 48 seconds.

PMID- 29065641
TI  - Biomechanical Effects of Various Bone-Implant Interfaces on the Stability of
      Orthodontic Miniscrews: A Finite Element Study.
AB  - INTRODUCTION: Osseointegration is required for prosthetic implant, but the
      various bone-implant interfaces of orthodontic miniscrews would be a great
      interest for the orthodontist. There is no clear consensus regarding the minimum
      amount of bone-implant osseointegration required for a stable miniscrew. The
      objective of this study was to investigate the influence of different bone
      implant interfaces on the miniscrew and its surrounding tissue. METHODS: Using
      finite element analysis, an advanced approach representing the bone-implant
      interface is adopted herein, and different degrees of bone-implant
      osseointegration were implemented in the FE models. A total of 26 different FE
      analyses were performed. The stress/strain patterns were calculated and compared,
      and the displacement of miniscrews was also evaluated. RESULTS: The stress/strain
      distributions are changing with the various bone-implant interfaces. In the
      scenario of 0% osseointegration, a rather homogeneous distribution was predicted.
      After 15% osseointegration, the stress/strains were gradually concentrated on the
      cortical bone region. The miniscrew experienced the largest displacement under
      the no osseointegra condition. The maximum displacement decreases sharply from 0%
      to 3% and tends to become stable. CONCLUSION: From a biomechanical perspective,
      it can be suggested that orthodontic loading could be applied on miniscrews after
      about 15% osseointegration without any loss of stability.

PMID- 29065643
TI  - Experimental Simulation-Based Performance Evaluation of an SMS-Based Emergency
      Geolocation Notification System.
AB  - In an emergency, a prompt response can save the lives of victims. This statement
      generates an imperative issue in emergency medical services (EMS). Designing a
      system that brings simplicity in locating emergency scenes is a step towards
      improving response time. This paper therefore implemented and evaluated the
      performance of an SMS-based emergency geolocation notification system with
      emphasis on its SMS delivery time and the system's geolocation and dispatch time.
      Using the RAS metrics recommended by IEEE for evaluation, the designed system was
      found to be efficient and effective as its reliability stood within 62.7% to
      70.0% while its availability stood at 99% with a downtime of 3.65 days/year.

PMID- 29065644
TI  - Computer-Aided Clinical Trial Recruitment Based on Domain-Specific Language
      Translation: A Case Study of Retinopathy of Prematurity.
AB  - Reusing the data from healthcare information systems can effectively facilitate
      clinical trials (CTs). How to select candidate patients eligible for CT
      recruitment criteria is a central task. Related work either depends on DBA
      (database administrator) to convert the recruitment criteria to native SQL
      queries or involves the data mapping between a standard ontology/information
      model and individual data source schema. This paper proposes an alternative
      computer-aided CT recruitment paradigm, based on syntax translation between
      different DSLs (domain-specific languages). In this paradigm, the CT recruitment
      criteria are first formally represented as production rules. The referenced rule
      variables are all from the underlying database schema. Then the production rule
      is translated to an intermediate query-oriented DSL (e.g., LINQ). Finally, the
      intermediate DSL is directly mapped to native database queries (e.g., SQL)
      automated by ORM (object-relational mapping).

PMID- 29065645
TI  - Effect of Graded Facetectomy on Lumbar Biomechanics.
AB  - Facetectomy is an important intervention for spinal stenosis but may lead to
      spinal instability. Biomechanical knowledge for facetectomy can be beneficial
      when deciding whether fusion is necessary. Therefore, the aim of this study was
      to investigate the biomechanical effect of different grades of facetectomy. A
      three-dimensional nonlinear finite element model of L3-L5 was constructed. The
      mobility of the model and the intradiscal pressure (IDP) of L4-L5 for standing
      were inside the data from the literature. The effect of graded facetectomy on
      intervertebral rotation, IDP, facet joint forces, and maximum von Mises
      equivalent stresses in the annuli was analyzed under flexion, extension,
      left/right lateral bending, and left/right axial rotation. Compared with the
      intact model, under extension, unilateral facetectomy increased the range of
      intervertebral rotation (IVR) by 11.7% and IDP by 10.7%, while the bilateral
      facetectomy increased IVR by 40.7% and IDP by 23.6%. Under axial rotation, the
      unilateral facetectomy and the bilateral facetectomy increased the IVR by 101.3%
      and 354.3%, respectively, when turned to the right and by 1.1% and 265.3%,
      respectively, when turned to the left. The results conclude that, after
      unilateral and bilateral facetectomy, care must be taken when placing the spine
      into extension and axial rotation posture from the biomechanical point of view.

PMID- 29065646
TI  - Design and Fabrication of Smart Diapers with Antibacterial Yarn.
AB  - In this study, intelligent eco-diapers are made by combining antibacterial yarns
      coated with quaternary ammonium salts with conductive yarns to improve caretaking
      for urinary incontinence. The combination of conductive yarns and sensors can
      detect the moisture content in eco-diapers, and an alarm is sent when moisture is
      significant. A wireless module is used to send detected signals to a smartphone
      or tablet PC via the Internet. This concept is used for a scenario in which
      nurses do not randomly check on patients in a long-term care institution. When
      used offline, eco-diapers can send caregivers an alarm for the need to change
      diapers via cell phones. The diameters of the copper and silver-plated copper
      fibers are 0.08 and 0.10 mm, respectively. Cotton yarns are twisted with copper
      and silver-plated copper fibers to form the conductive yarns, which are 0.12 mm
      in diameter. Moreover, 30-count cotton and 150 D nylon yarns are coated with
      quaternary ammonium salt via dyeing and finishing processes to form antibacterial
      yarns. In the current study, intelligent eco-diapers are tested for their
      electrical and antibacterial properties as specified by AATC and JISL test
      standards.

PMID- 29065642
TI  - The Use of Optical Coherence Tomography in Dental Diagnostics: A State-of-the-Art
      Review.
AB  - Optical coherence tomography provides sections of tissues in a noncontact and
      noninvasive manner. The device measures the time delay and intensity of the light
      scattered or reflected from biological tissues, which results in tomographic
      imaging of their internal structure. This is achieved by scanning tissues at a
      resolution ranging from 1 to 15 MUm. OCT enables real-time in situ imaging of
      tissues without the need for biopsy, histological procedures, or the use of X
      rays, so it can be used in many fields of medicine. Its properties are not only
      particularly used in ophthalmology, in the diagnosis of all layers of the retina,
      but also increasingly in cardiology, gastroenterology, pulmonology, oncology, and
      dermatology. The basic properties of OCT, that is, noninvasiveness and low
      wattage of the used light, have also been appreciated in analytical technology by
      conservators, who use it to identify the quality and age of paintings, ceramics,
      or glass. Recently, the OCT technique of visualization is being tested in
      different fields of dentistry, which is depicted in the article.

PMID- 29065647
TI  - An Ensemble Multilabel Classification for Disease Risk Prediction.
AB  - It is important to identify and prevent disease risk as early as possible through
      regular physical examinations. We formulate the disease risk prediction into a
      multilabel classification problem. A novel Ensemble Label Power-set Pruned
      datasets Joint Decomposition (ELPPJD) method is proposed in this work. First, we
      transform the multilabel classification into a multiclass classification. Then,
      we propose the pruned datasets and joint decomposition methods to deal with the
      imbalance learning problem. Two strategies size balanced (SB) and label
      similarity (LS) are designed to decompose the training dataset. In the
      experiments, the dataset is from the real physical examination records. We
      contrast the performance of the ELPPJD method with two different decomposition
      strategies. Moreover, the comparison between ELPPJD and the classic multilabel
      classification methods RAkEL and HOMER is carried out. The experimental results
      show that the ELPPJD method with label similarity strategy has outstanding
      performance.

PMID- 29065648
TI  - Semiautomatic Segmentation of Glioma on Mobile Devices.
AB  - Brain tumor segmentation is the first and the most critical step in clinical
      applications of radiomics. However, segmenting brain images by radiologists is
      labor intense and prone to inter- and intraobserver variability. Stable and
      reproducible brain image segmentation algorithms are thus important for
      successful tumor detection in radiomics. In this paper, we propose a supervised
      brain image segmentation method, especially for magnetic resonance (MR) brain
      images with glioma. This paper uses hard edge multiplicative intrinsic component
      optimization to preprocess glioma medical image on the server side, and then, the
      doctors could supervise the segmentation process on mobile devices in their
      convenient time. Since the preprocessed images have the same brightness for the
      same tissue voxels, they have small data size (typically 1/10 of the original
      image size) and simple structure of 4 types of intensity value. This observation
      thus allows follow-up steps to be processed on mobile devices with low bandwidth
      and limited computing performance. Experiments conducted on 1935 brain slices
      from 129 patients show that more than 30% of the sample can reach 90% similarity;
      over 60% of the samples can reach 85% similarity, and more than 80% of the sample
      could reach 75% similarity. The comparisons with other segmentation methods also
      demonstrate both efficiency and stability of the proposed approach.

PMID- 29065650
TI  - Fall Prevention Shoes Using Camera-Based Line-Laser Obstacle Detection System.
AB  - Fall prevention is an important issue particularly for the elderly. This paper
      proposes a camera-based line-laser obstacle detection system to prevent falls in
      the indoor environment. When obstacles are detected, the system will emit alarm
      messages to catch the attention of the user. Because the elderly spend a lot of
      their time at home, the proposed line-laser obstacle detection system is designed
      mainly for indoor applications. Our obstacle detection system casts a laser line,
      which passes through a horizontal plane and has a specific height to the ground.
      A camera, whose optical axis has a specific inclined angle to the plane, will
      observe the laser pattern to obtain the potential obstacles. Based on this
      configuration, the distance between the obstacles and the system can be further
      determined by a perspective transformation called homography. After conducting
      the experiments, critical parameters of the algorithms can be determined, and the
      detected obstacles can be classified into different levels of danger, causing the
      system to send different alarm messages.

PMID- 29065649
TI  - Antagonist Muscle Prefatigue Increases the Intracortical Communication between
      Contralateral Motor Cortices during Elbow Extension Contraction.
AB  - To investigate the cortico-cortical coupling changes related to antagonist muscle
      prefatigue, we recorded EEG at FC3, C3, FC4, and C4 electrodes of twelve young
      male volunteers during a 30-second-long, nonfatiguing isometric elbow extension
      contraction with a target force level of 20% MVC before and after a sustained
      fatiguing elbow flexion contraction until task failure. EEG-EEG phase
      synchronization indices in alpha and beta frequency bands were calculated for the
      pre- and postfatigue elbow extension contractions. The phase synchronization
      index in the beta frequency band was found significantly increased between EEG of
      FC3-C3. The increased phase synchronization index may reflect an enhanced
      intracortical communication or integration of the signals between contralateral
      motor cortices with antagonist muscle prefatigue, which may be related to the
      central modulation so as to compensate for the antagonist muscle prefatigue
      induced joint instability.

PMID- 29065651
TI  - Using Deep Learning for Classification of Lung Nodules on Computed Tomography
      Images.
AB  - Lung cancer is the most common cancer that cannot be ignored and cause death with
      late health care. Currently, CT can be used to help doctors detect the lung
      cancer in the early stages. In many cases, the diagnosis of identifying the lung
      cancer depends on the experience of doctors, which may ignore some patients and
      cause some problems. Deep learning has been proved as a popular and powerful
      method in many medical imaging diagnosis areas. In this paper, three types of
      deep neural networks (e.g., CNN, DNN, and SAE) are designed for lung cancer
      calcification. Those networks are applied to the CT image classification task
      with some modification for the benign and malignant lung nodules. Those networks
      were evaluated on the LIDC-IDRI database. The experimental results show that the
      CNN network archived the best performance with an accuracy of 84.15%, sensitivity
      of 83.96%, and specificity of 84.32%, which has the best result among the three
      networks.

PMID- 29065652
TI  - Intraoral Scanner Technologies: A Review to Make a Successful Impression.
AB  - To overcome difficulties associated with conventional techniques, impressions
      with IOS (intraoral scanner) and CAD/CAM (computer-aided design and
      manufacturing) technologies were developed for dental practice. The last decade
      has seen an increasing number of optical IOS devices, and these are based on
      different technologies; the choice of which may impact on clinical use. To allow
      informed choice before purchasing or renewing an IOS, this article summarizes
      first the technologies currently used (light projection, distance object
      determination, and reconstruction). In the second section, the clinical
      considerations of each strategy such as handling, learning curve, powdering,
      scanning paths, tracking, and mesh quality are discussed. The last section is
      dedicated to the accuracy of files and of the intermaxillary relationship
      registered with IOS as the rendering of files in the graphical user interface is
      often misleading. This overview leads to the conclusion that the current IOS is
      adapted for a common practice, although differences exist between the
      technologies employed. An important aspect highlighted in this review is the
      reduction in the volume of hardware which has led to an increase in the
      importance of software-based technologies.

PMID- 29065653
TI  - A Mechanical Sensor Designed for Dynamic Joint Angle Measurement.
AB  - Background. The measurement of the functional range of motion (FROM) of lower
      limb joints is an essential parameter for gait analysis especially in evaluating
      rehabilitation programs. Aim. To develop a simple, reliable, and affordable
      mechanical goniometer (MGR) for gait analysis, with six-degree freedom to
      dynamically assess lower limb joint angles. Design. Randomized control trials, in
      which a new MGR was developed for the measurements of FROM of lower limb joints.
      Setting. Reliability of the designed MGR was evaluated and validated by a motion
      analysis system (MAS). Population. Thirty healthy subjects participated in this
      study. Methods. Reliability and validity of the new MGR were tested by intraclass
      correlation coefficient (ICC), Bland-Altman plots, and linear correlation
      analysis. Results. The MGR has good inter- and intrarater reliability and
      validity with ICC >= 0.93 (for both). Moreover, measurements made by MGR and MAS
      were comparable and repeatable with each other, as confirmed by Bland-Altman
      plots. Furthermore, a very high degree of linear correlation (R >= 0.92 for all
      joint angle measurements) was found between the lower limb joint angles measured
      by MGR and MAS. Conclusion. A simple, reliable, and affordable MGR has been
      designed and developed to aid clinical assessment and treatment evaluation of
      gait disorders.

PMID- 29065654
TI  - Biomechanical Property of a Newly Designed Assembly Locking Compression Plate:
      Three-Dimensional Finite Element Analysis.
AB  - In this study, we developed and validated a refined three-dimensional finite
      element model of middle femoral comminuted fracture to compare the biomechanical
      stability after two kinds of plate fixation: a newly designed assembly locking
      compression plate (NALCP) and a locking compression plate (LCP). CT data of a
      male volunteer was converted to middle femoral comminuted fracture finite element
      analysis model. The fracture was fixated by NALCP and LCP. Stress distributions
      were observed. Under slow walking load and torsion load, the stress distribution
      tendency of the two plates was roughly uniform. The anterolateral femur was the
      tension stress area, and the bone block shifted toward the anterolateral femur.
      Maximum stress was found on the lateral border of the number 5 countersink of the
      plate. Under a slow walking load, the NALCP maximum stress was 2.160e+03 MPa and
      the LCP was 8.561e+02 MPa. Under torsion load, the NALCP maximum stress was
      2.260e+03 MPa and the LCP was 6.813e+02 MPa. Based on those results of finite
      element analysis, the NALCP can provide adequate mechanical stability for
      comminuted fractures, which would help fixate the bone block and promote bone
      healing.

PMID- 29065655
TI  - The Effect of Arch Height and Material Hardness of Personalized Insole on
      Correction and Tissues of Flatfoot.
AB  - Flat foot is one of the common deformities in the youth population, seriously
      affecting the weight supporting and daily exercising. However, there is lacking
      of quantitative data relative to material selection and shape design of the
      personalized orthopedic insole. This study was to evaluate the biomechanical
      effects of material hardness and support height of personalized orthopedic insole
      on foot tissues, by in vivo experiment and finite element modeling. The
      correction of arch height increased with material hardness and support height.
      The peak plantar pressure increased with the material hardness, and these values
      by wearing insoles of 40 degrees  were apparently higher than the bare feet
      condition. Harder insole material results in higher stress in the joint and
      ligament stress than softer material. In the calcaneocuboid joint, the stress
      increased with the arch height of insoles. The material hardness did not
      apparently affect the stress in the ankle joints, but the support heights of
      insole did. In general, insole material and support design are positively
      affecting the correction of orthopedic insole, but negatively resulting in
      unreasonable stress on the stress in the joint and ligaments. There should be an
      integration of improving correction and reducing stress in foot tissues.

PMID- 29065656
TI  - Multimodal Image Alignment via Linear Mapping between Feature Modalities.
AB  - We propose a novel landmark matching based method for aligning multimodal images,
      which is accomplished uniquely by resolving a linear mapping between different
      feature modalities. This linear mapping results in a new measurement on
      similarity of images captured from different modalities. In addition, our method
      simultaneously solves this linear mapping and the landmark correspondences by
      minimizing a convex quadratic function. Our method can estimate complex image
      relationship between different modalities and nonlinear nonrigid spatial
      transformations even in the presence of heavy noise, as shown in our experiments
      carried out by using a variety of image modalities.

PMID- 29065657
TI  - Therapy Decision Support Based on Recommender System Methods.
AB  - We present a system for data-driven therapy decision support based on techniques
      from the field of recommender systems. Two methods for therapy recommendation,
      namely, Collaborative Recommender and Demographic-based Recommender, are
      proposed. Both algorithms aim to predict the individual response to different
      therapy options using diverse patient data and recommend the therapy which is
      assumed to provide the best outcome for a specific patient and time, that is,
      consultation. The proposed methods are evaluated using a clinical database
      incorporating patients suffering from the autoimmune skin disease psoriasis. The
      Collaborative Recommender proves to generate both better outcome predictions and
      recommendation quality. However, due to sparsity in the data, this approach
      cannot provide recommendations for the entire database. In contrast, the
      Demographic-based Recommender performs worse on average but covers more
      consultations. Consequently, both methods profit from a combination into an
      overall recommender system.

PMID- 29065658
TI  - Atlas-Free Cervical Spinal Cord Segmentation on Midsagittal T2-Weighted Magnetic
      Resonance Images.
AB  - An automatic atlas-free method for segmenting the cervical spinal cord on
      midsagittal T2-weighted magnetic resonance images (MRI) is presented. Pertinent
      anatomical knowledge is transformed into constraints employed at different stages
      of the algorithm. After picking up the midsagittal image, the spinal cord is
      detected using expectation maximization and dynamic programming (DP). Using DP,
      the anterior and posterior edges of the spinal canal and the vertebral column are
      detected. The vertebral bodies and the intervertebral disks are then segmented
      using region growing. Then, the anterior and posterior edges of the spinal cord
      are detected using median filtering followed by DP. We applied this method to 79
      noncontrast MRI studies over a 3-month period. The spinal cords were detected in
      all cases, and the vertebral bodies were successfully labeled in 67 (85%) of
      them. Our algorithm had very good performance. Compared to manual segmentation
      results, the Jaccard indices ranged from 0.937 to 1, with a mean of 0.980 +/-
      0.014. The Hausdorff distances between the automatically detected and manually
      delineated anterior and posterior spinal cord edges were both 1.0 +/- 0.5 mm.
      Used alone or in combination, our method lays a foundation for computer-aided
      diagnosis of spinal diseases, particularly cervical spondylotic myelopathy.

PMID- 29065659
TI  - Morphological and Microstructural Alterations of the Articular Cartilage and
      Bones during Treadmill Exercises with Different Additional Weight-Bearing Levels.
AB  - The aim of this study was to investigate the morphological and microstructural
      alterations of the articular cartilage and bones during treadmill exercises with
      different exercise intensities. Sixty 5-week-old female rats were randomly
      divided into 10 groups: five additional weight-bearing groups (WBx) and five
      additional weight-bearing with treadmill exercise groups (EBx), which were
      subjected to additional weight bearing of x% (x = 0, 5, 12, 19, and 26) of the
      corresponding body weight of each rat for 15 min/day. After 8 weeks of
      experiment, the rats were humanely sacrificed and their bilateral intact knee
      joints were harvested. Morphological analysis of the cartilages and microcomputed
      tomography evaluation of bones were subsequently performed. Results showed that
      increased additional weight bearing may lead to cartilage damage. No significant
      difference was observed among the subchondral cortical thicknesses of the groups.
      The microstructure of subchondral trabecular bone of 12% and 19% additional
      weight-bearing groups was significantly improved; however, the WB26 and EB26
      groups showed low bone mineral density and bone volume fraction as well as high
      structure model index. In conclusion, effects of treadmill exercise on joints may
      be associated with different additional weight-bearing levels, and exercise
      intensities during joint growth and maturation should be selected reasonably.

PMID- 29065660
TI  - Twin SVM-Based Classification of Alzheimer's Disease Using Complex Dual-Tree
      Wavelet Principal Coefficients and LDA.
AB  - Alzheimer's disease (AD) is a leading cause of dementia, which causes serious
      health and socioeconomic problems. A progressive neurodegenerative disorder,
      Alzheimer's causes the structural change in the brain, thereby affecting
      behavior, cognition, emotions, and memory. Numerous multivariate analysis
      algorithms have been used for classifying AD, distinguishing it from healthy
      controls (HC). Efficient early classification of AD and mild cognitive impairment
      (MCI) from HC is imperative as early preventive care could help to mitigate risk
      factors. Magnetic resonance imaging (MRI), a noninvasive biomarker, displays
      morphometric differences and cerebral structural changes. A novel approach for
      distinguishing AD from HC using dual-tree complex wavelet transforms (DTCWT),
      principal coefficients from the transaxial slices of MRI images, linear
      discriminant analysis, and twin support vector machine is proposed here. The
      prediction accuracy of the proposed method yielded up to 92.65 +/- 1.18 over the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, with a specificity of
      92.19 +/- 1.56 and sensitivity of 93.11 +/- 1.29, and 96.68 +/- 1.44 over the
      Open Access Series of Imaging Studies (OASIS) dataset, with a sensitivity of
      97.72 +/- 2.34 and specificity of 95.61 +/- 1.67. The accuracy, sensitivity, and
      specificity achieved using the proposed method are comparable or superior to
      those obtained by various conventional AD prediction methods.

PMID- 29065661
TI  - Joint Torque and Mechanical Power of Lower Extremity and Its Relevance to
      Hamstring Strain during Sprint Running.
AB  - The aim of this study was to quantify the contributions of lower extremity joint
      torques and the mechanical power of lower extremity muscle groups to further
      elucidate the loadings on hamstring and the mechanics of its injury. Eight
      national-level male sprinters performed maximum-velocity sprint running on a
      synthetic track. The 3D kinematic data and ground reaction force (GRF) were
      collected synchronously. Intersegmental dynamics approach was used to analyze the
      lower extremity joint torques and power changes in the lower extremity joint
      muscle groups. During sprinting, the GRF during the stance phase and the motion
      dependent torques (MDT) during the swing phase had a major effect on the lower
      extremity movements and muscle groups. Specifically, during the stance phase,
      torque produced and work performed by the hip and knee muscles were generally
      used to counteract the GRF. During the swing phase, the role of the muscle torque
      changed to mainly counteract the effect of MDT to control the movement direction
      of the lower extremity. Meanwhile, during the initial stance and late swing
      phases, the passive torques, namely, the ground reaction torques and MDT produced
      by the GRF and the inertial movement of the segments of the lower extremity,
      applied greater stress to the hamstring muscles.

PMID- 29065662
TI  - An Open-Structure Treadmill Gait Trainer: From Research to Application.
AB  - Lower limb rehabilitation robots are designed to enhance gait function in
      individuals with motor impairments. Although numerous rehabilitation robots have
      been developed, only few of these robots have been used in practical health care,
      particularly in China. The objective of this study is to construct a lower limb
      rehabilitation robot and bridge the gap between research and application. Open
      structure to facilitate practical application was created for the whole robot.
      Three typical movement patterns of a single leg were adopted in designing the
      exoskeletons, and force models for patient training were established and analyzed
      under three different conditions, respectively, and then a control system and
      security strategy were introduced. After establishing the robot, a preliminary
      experiment on the actual use of a prototype by patients was conducted to validate
      the functionality of the robot. The experiment showed that different patients and
      stages displayed different performances, and results on the trend variations
      across patients and across stages confirmed the validity of the robot and
      suggested that the design may lead to a system that could be successful in the
      treatment of patients with walking disorders in China. Furthermore, this study
      could provide a reference for a similar application design.

PMID- 29065663
TI  - Diagnosis of Alzheimer's Disease Using Dual-Tree Complex Wavelet Transform, PCA,
      and Feed-Forward Neural Network.
AB  - Background. Error-free diagnosis of Alzheimer's disease (AD) from healthy control
      (HC) patients at an early stage of the disease is a major concern, because
      information about the condition's severity and developmental risks present allows
      AD sufferer to take precautionary measures before irreversible brain damage
      occurs. Recently, there has been great interest in computer-aided diagnosis in
      magnetic resonance image (MRI) classification. However, distinguishing between
      Alzheimer's brain data and healthy brain data in older adults (age > 60) is
      challenging because of their highly similar brain patterns and image intensities.
      Recently, cutting-edge feature extraction technologies have found extensive
      application in numerous fields, including medical image analysis. Here, we
      propose a dual-tree complex wavelet transform (DTCWT) for extracting features
      from an image. The dimensionality of feature vector is reduced by using principal
      component analysis (PCA). The reduced feature vector is sent to feed-forward
      neural network (FNN) to distinguish AD and HC from the input MR images. These
      proposed and implemented pipelines, which demonstrate improvements in
      classification output when compared to that of recent studies, resulted in high
      and reproducible accuracy rates of 90.06 +/- 0.01% with a sensitivity of 92.00 +/
      0.04%, a specificity of 87.78 +/- 0.04%, and a precision of 89.6 +/- 0.03% with
      10-fold cross-validation.

PMID- 29065664
TI  - Development of an Omnidirectional-Capable Electromagnetic Shock Wave Generator
      for Lipolysis.
AB  - Traditional methods for adipose tissue removal have progressed from invasive
      methods such as liposuction to more modern methods of noninvasive lipolysis. This
      research entails the development and evaluation of an omnidirectional-capable
      flat-coil electromagnetic shock wave generator (EMSWG) for lipolysis. The
      developed EMSWG has the advantage of omnidirectional-capable operation. This
      capability increases the eventual clinical usability by adding three designed
      supports to the aluminum disk of the EMSWG to allow omnidirectional operation.
      The focal pressures of the developed EMSWG for different operating voltages were
      measured, and its corresponding energy intensities were calculated. The developed
      EMSWG was mounted in a downward orientation for lipolysis and evaluated as proof
      of concept. In vitro tests on porcine fatty tissues have been carried out. It is
      found that at a 6 kV operating voltage with 1500 shock wave exposures, a 2 cm
      thick subcutaneous hypodermis of porcine fatty tissue can be ruptured, resulting
      in a damaged area of 1.39 mm2. At a 6.5 kV operating voltage with 2000 shock wave
      exposures, the damaged area is increased to about 5.20 mm2, which can be enlarged
      by changing the focal point location, resulting in significant lipolysis for use
      in clinical applications.

PMID- 29065665
TI  - Numerical Investigation on the Biomechanical Performance of Laparoscopic-Assisted
      Plate Used for Fixing Pelvic Anterior Ring Fracture.
AB  - Because of the minimal soft tissue injury, the laparoscopic-assisted internal
      fixation is a promising technique in fixing the pelvic anterior ring fracture.
      The aim of this study was to investigate the biomechanical performance of the
      laparoscopic-assisted plate by the finite element method. Four kinds of implants
      were investigated, that is, the laparoscopic-assisted plate (LAP), the
      percutaneous anterior pelvic bridge (PAPB), the transramus intraosseous screw
      (TIS), and the open reduction (OR). The stability of the implants was
      investigated under three loading cases, showing that when the LAP was used, the
      stress at the fracture site was smaller than that at other parts, while for other
      implants, the high stress was always around the fracture site. In conclusion, the
      LAP demonstrated a good biomechanical performance in fixing the pelvic anterior
      ring fracture and is a promising technique in clinical applications.

PMID- 29065666
TI  - Low-Grade Glioma Segmentation Based on CNN with Fully Connected CRF.
AB  - This work proposed a novel automatic three-dimensional (3D) magnetic resonance
      imaging (MRI) segmentation method which would be widely used in the clinical
      diagnosis of the most common and aggressive brain tumor, namely, glioma. The
      method combined a multipathway convolutional neural network (CNN) and fully
      connected conditional random field (CRF). Firstly, 3D information was introduced
      into the CNN which makes more accurate recognition of glioma with low contrast.
      Then, fully connected CRF was added as a postprocessing step which purposed more
      delicate delineation of glioma boundary. The method was applied to T2flair MRI
      images of 160 low-grade glioma patients. With 59 cases of data training and
      manual segmentation as the ground truth, the Dice similarity coefficient (DSC) of
      our method was 0.85 for the test set of 101 MRI images. The results of our method
      were better than those of another state-of-the-art CNN method, which gained the
      DSC of 0.76 for the same dataset. It proved that our method could produce better
      results for the segmentation of low-grade gliomas.

PMID- 29065667
TI  - Nonrigid Registration of Prostate Diffusion-Weighted MRI.
AB  - Motion and deformation are common in prostate diffusion-weighted magnetic
      resonance imaging (DWI) during acquisition. These misalignments lead to errors in
      estimating an apparent diffusion coefficient (ADC) map fitted with DWI. To
      address this problem, we propose an image registration algorithm to align the
      prostate DWI and improve ADC map. First, we apply affine transformation to DWI to
      correct intraslice motions. Then, nonrigid registration based on free-form
      deformation (FFD) is used to compensate for intraimage deformations. To evaluate
      the influence of the proposed algorithm on ADC values, we perform statistical
      experiments in three schemes: no processing of the DWI, with the affine transform
      approach, and with FFD. The experimental results show that our proposed algorithm
      can correct the misalignment of prostate DWI and decrease the artifacts of ROI in
      the ADC maps. These ADC maps thus obtain sharper contours of lesions, which are
      helpful for improving the diagnosis and clinical staging of prostate cancer.

PMID- 29065668
TI  - How Arch Support Insoles Help Persons with Flatfoot on Uphill and Downhill
      Walking.
AB  - The main purpose of this study was to investigate the effect of arch support
      insoles on uphill and downhill walking of persons with flatfoot. Sixteen healthy
      college students with flatfoot were recruited in this study. Their heart rate,
      peak oxygen uptake (VO2), and median frequency (MDF) of surface electromyogram
      were recorded and analyzed. Nonparametric Wilcoxon signed-rank test was used for
      statistical analysis. The main results were as follows: (a) peak VO2
      significantly decreased with arch support insoles compared with flat insoles
      during uphill and downhill walking (arch support insole versus flat insole:
      uphill walking, 20.7 +/- 3.6 versus 31.6 +/- 5.5; downhill walking, 10.9 +/- 2.3
      versus 16.9 +/- 4.2); (b) arch support insoles could reduce the fatigue of the
      rectus femoris muscle during downhill walking (MDF slope of arch support insole:
      0.03 +/- 1.17, flat insole: -6.56 +/- 23.07); (c) insole hardness would increase
      not only the physical sensory input but also the fatigue of lower-limb muscles
      particularly for the rectus femoris muscle (MDF slope of arch support insole: 
      1.90 +/- 1.60, flat insole: -0.83 +/- 1.10) in persons with flatfoot during
      uphill walking. The research results show that arch support insoles could
      effectively be applied to persons with flatfoot to aid them during uphill and
      downhill walking.

PMID- 29065669
TI  - A Granular Ontology Model for Maternal and Child Health Information System.
AB  - In several developing countries, maternal and child health indicators trail
      behind the international targets set by the UN as Millennium or Sustainable
      Development Goals. One of the reasons is poor and nonstandardized maternal health
      record keeping that affects data quality. Effective decision making to improve
      public healthcare depends essentially on the availability of reliable data.
      Therefore, the aim of this research is the design and development of the standard
      compliant data access model for maintaining maternal and child health data to
      enable the effective exchange of healthcare data. The proposed model is very
      granular and comprehensive in contrast with existing systems. To evaluate the
      effectiveness of the model, a web application was implemented and was reviewed by
      healthcare providers and expectant mothers. User feedback highlights the
      usefulness of the proposed approach as compared to traditional record-keeping
      techniques. It is anticipated that the proposed model will lay a foundation for a
      comprehensive maternal and child healthcare information system. This shall enable
      trend analysis for policy making to help accelerate the efforts for meeting
      global maternal and child health targets.

PMID- 29065670
TI  - Gentamicin Released from Porous Scaffolds Fabricated by Stereolithography.
AB  - Porous oligolactide-hydroxyapatite composite scaffolds were obtained by
      stereolithographic fabrication. Gentamicin was then coated on the scaffolds
      afterwards, to achieve antimicrobial delivery ability to treat bone infection.
      The scaffolds examined by stereomicroscope, SEM, and MUCT-scan showed a well
      ordered pore structure with uniform pore distribution and pore interconnectivity.
      The physical and mechanical properties of the scaffolds were investigated. It was
      shown that not only porosity but also scaffold structure played a critical role
      in governing the strength of scaffolds. A good scaffold design could create
      proper orientation of pores in a way to strengthen the scaffold structure. The
      drug delivery profile of the porous scaffolds was also analyzed using
      microbiological assay. The release rates of gentamicin from the scaffolds showed
      prolonged drug release at the levels higher than the minimum inhibitory
      concentrations for S. aureus and E. coli over a 2-week period. It indicated a
      potential of the scaffolds to serve as local antibiotic delivery to prevent
      bacterial infection.

PMID- 29065671
TI  - A Kalman Filtering and Nonlinear Penalty Regression Approach for Noninvasive
      Anemia Detection with Palpebral Conjunctiva Images.
AB  - Noninvasive medical procedures are usually preferable to their invasive
      counterparts in the medical community. Anemia examining through the palpebral
      conjunctiva is a convenient noninvasive procedure. The procedure can be automated
      to reduce the medical cost. We propose an anemia examining approach by using a
      Kalman filter (KF) and a regression method. The traditional KF is often used in
      time-dependent applications. Here, we modified the traditional KF for the time
      independent data in medical applications. We simply compute the mean value of the
      red component of the palpebral conjunctiva image as our recognition feature and
      use a penalty regression algorithm to find a nonlinear curve that best fits the
      data of feature values and the corresponding levels of hemoglobin (Hb)
      concentration. To evaluate the proposed approach and several relevant approaches,
      we propose a risk evaluation scheme, where the entire Hb spectrum is divided into
      high-risk, low-risk, and doubtful intervals for anemia. The doubtful interval
      contains the Hb threshold, say 11 g/dL, separating anemia and nonanemia. A
      suspect sample is the sample falling in the doubtful interval. For the anemia
      screening purpose, we would like to have as less suspect samples as possible. The
      experimental results show that the modified KF reduces the number of suspect
      samples significantly for all the approaches considered here.

PMID- 29065672
TI  - The Effects of Physiological Biomechanical Loading on Intradiscal Pressure and
      Annulus Stress in Lumbar Spine: A Finite Element Analysis.
AB  - The present study was conducted to examine the effects of body weight on
      intradiscal pressure (IDP) and annulus stress of intervertebral discs at lumbar
      spine. Three-dimensional finite element model of osseoligamentous lumbar spine
      was developed subjected to follower load of 500 N, 800 N, and 1200 N which
      represent the loads for individuals who are normal and overweight with the pure
      moments at 7.5 Nm in flexion and extension motions. It was observed that the
      maximum IDP was 1.26 MPa at L1-L2 vertebral segment. However, the highest
      increment of IDP was found at L4-L5 segment where the IDP was increased to 30% in
      flexion and it was more severe at extension motion reaching to 80%. Furthermore,
      the maximum annulus stress also occurred at the L1-L2 segment with 3.9 MPa in
      extension motion. However, the highest increment was also found at L4-L5 where
      the annulus stress increased to 17% in extension motion. Based on these results,
      the increase of physiological loading could be an important factor to the
      increment of intradiscal pressure and annulus fibrosis stress at all
      intervertebral discs at the lumbar spine which may lead to early intervertebral
      disc damage.

PMID- 29065673
TI  - Evaluating the Relationship between Productivity and Quality in Emergency
      Departments.
AB  - BACKGROUND: In the United States, emergency departments (EDs) are constantly
      pressured to improve operational efficiency and quality in order to gain
      financial benefits and maintain a positive reputation. OBJECTIVES: The first
      objective is to evaluate how efficiently EDs transform their input resources into
      quality outputs. The second objective is to investigate the relationship between
      the efficiency and quality performance of EDs and the factors affecting this
      relationship. METHODS: Using two data sources, we develop a data envelopment
      analysis (DEA) model to evaluate the relative efficiency of EDs. Based on the DEA
      result, we performed multinomial logistic regression to investigate the
      relationship between ED efficiency and quality performance. RESULTS: The DEA
      results indicated that the main source of inefficiencies was working hours of
      technicians. The multinomial logistic regression result indicated that the number
      of electrocardiograms and X-ray procedures conducted in the ED and the length of
      stay were significantly associated with the trade-offs between relative
      efficiency and quality. Structural ED characteristics did not influence the
      relationship between efficiency and quality. CONCLUSIONS: Depending on the
      structural and operational characteristics of EDs, different factors can affect
      the relationship between efficiency and quality.

PMID- 29065674
TI  - Two-Segment Foot Model for the Biomechanical Analysis of Squat.
AB  - Squat exercise is acquiring interest in many fields, due to its benefits in
      improving health and its biomechanical similarities to a wide range of sport
      motions and the recruitment of many body segments in a single maneuver. Several
      researches had examined considerable biomechanical aspects of lower limbs during
      squat, but not without limitations. The main goal of this study focuses on the
      analysis of the foot contribution during a partial body weight squat, using a two
      segment foot model that considers separately the forefoot and the hindfoot. The
      forefoot and hindfoot are articulated by the midtarsal joint. Five subjects
      performed a series of three trials, and results were averaged. Joint kinematics
      and dynamics were obtained using motion capture system, two force plates closed
      together, and inverse dynamics techniques. The midtarsal joint reached a
      dorsiflexion peak of 4 degrees . Different strategies between subjects revealed 4
      degrees  supination and 2.5 degrees  pronation of the forefoot. Vertical GRF
      showed 20% of body weight concentrated on the forefoot and 30% on the hindfoot.
      The percentages varied during motion, with a peak of 40% on the hindfoot and
      correspondently 10% on the forefoot, while the traditional model depicted the
      unique constant 50% value. Ankle peak of plantarflexion moment, power absorption,
      and power generation was consistent with values estimated by the one-segment
      model, without statistical significance.

PMID- 29065675
TI  - Morphological, Immunocytochemical, and Biochemical Studies of Rat Costal
      Chondrocytes Exposed to IL-1beta and TGF-beta1.
AB  - This study was undertaken to determine the effects of IL-1beta and TGF-beta1 on
      the expression of differentiation-associated genes in chondrocytes in vitro. Rat
      costal chondrocytes were exposed to different concentrations of IL-1beta and TGF
      beta1 for 48 h and tested for gene expression. IL-1beta increased the expression
      of aggrecanase-1 and aggrecanase-2 and decreased the content of aggrecan and
      collagen II. Low concentration of TGF-beta1 decreased the expression of aggrecan
      and collagen II and increased the expression of aggrecanase-2. However, the level
      of aggrecanase-1 was significantly elevated in the presence of high concentration
      of TGF-beta1. IL-1beta and TGF-beta1 show the ability to modulate the production
      of aggrecan and collagen II in chondrocytes in vitro.

PMID- 29065676
TI  - Analysis of Cardiovascular Tissue Components for the Diagnosis of Coronary
      Vulnerable Plaque from Intravascular Ultrasound Images.
AB  - The purpose of this study was to characterize cardiovascular tissue components
      and analyze the different tissue properties for predicting coronary vulnerable
      plaque from intravascular ultrasound (IVUS) images. For this purpose, sequential
      IVUS image frames were obtained from human coronary arteries using 20 MHz
      catheters. The plaque regions between the intima and media-adventitial borders
      were manually segmented in all IVUS images. Tissue components of the plaque
      regions were classified into having fibrous tissue (FT), fibrofatty tissue (FFT),
      necrotic core (NC), or dense calcium (DC). The media area and lumen diameter were
      also estimated simultaneously. In addition, the external elastic membrane (EEM)
      was computed to predict the vulnerable plaque after the tissue characterization.
      The reliability of manual segmentation was validated in terms of inter- and
      intraobserver agreements. The quantitative results found that the FT and the
      media as well as the NC would be good indicators for predicting vulnerable
      plaques in IVUS images. In addition, the lumen was not suitable for early
      diagnosis of vulnerable plaque because of the low significance compared to the
      other vessel parameters. To predict vulnerable plaque rupture, future study
      should have additional experiments using various tissue components, such as the
      EEM, FT, NC, and media.

PMID- 29065678
TI  - Bilateral optic neuropathy related to severe anemia in a patient with alcoholic
      cirrhosis: a case report and review of the literature.
AB  - Anemia appears frequently in patients with alcoholic liver disease (ALD) but has
      never been linked to bilateral nonarteritic anterior ischemic optic neuropathy
      (NAION). A 65-year-old woman with a medical history of alcoholic cirrhosis was
      admitted for bilateral NAION. On admission, she was found to have a low arterial
      pressure and severe normocytic anemia (48 g/L). The anemia was related to chronic
      bleeding due to antral gastritis along with other factors associated with ALD.
      The applied treatment consisted of urgent transfusion followed by high doses of
      proton-pump inhibitors, iron and vitamin supplementation, and support in
      lifestyle measures. Her hemoglobin levels remained stable after 2 years but the
      patient still suffered from visual loss. This case highlights the link between
      anemia and bilateral NAION in ALD patients. The optic nerve head is prone to
      infarction in this context due to the vascularization characteristics of ALD.
      Hemoglobin levels should be monitored in ALD patients to avoid the severe
      complication of NAION.

PMID- 29065677
TI  - Developing a Low-Cost Force Treadmill via Dynamic Modeling.
AB  - By incorporating force transducers into treadmills, force platform-instrumented
      treadmills (commonly called force treadmills) can collect large amounts of gait
      data and enable the ground reaction force (GRF) to be calculated. However, the
      high cost of force treadmills has limited their adoption. This paper proposes a
      low-cost force treadmill system with force sensors installed underneath a
      standard exercise treadmill. It identifies and compensates for the force
      transmission dynamics from the actual GRF applied on the treadmill track surface
      to the force transmitted to the force sensors underneath the treadmill body. This
      study also proposes a testing procedure to assess the GRF measurement accuracy of
      force treadmills. Using this procedure in estimating the GRF of "walk-on-the-spot
      motion," it was found that the total harmonic distortion of the tested force
      treadmill system was about 1.69%, demonstrating the effectiveness of the
      approach.

PMID- 29065680
TI  - Scallop-Inspired DNA Nanomachine: A Ratiometric Nanothermometer for Intracellular
      Temperature Sensing.
AB  - Accurate measurement of intracellular temperature is of great significance in
      biology and medicine. With use of DNA nanotechnology and inspiration by nature's
      examples of "protective and reversible responses" exoskeletons, a scallop
      inspired DNA nanomachine (SDN) is desgined as a ratiometric nanothermometer for
      intracellular temperature sensing. The SDN is composed of a rigid DNA
      tetrahedron, where a thermal-sensitive molecular beacon (MB) is embedded in one
      edge of the DNA tetrahedron. Relying on the thermal-sensitive MB and fluorescence
      resonance energy transfer (FRET) signaling mechanism, the "On" to "Off" signal is
      reversibly responding to "below" and "over" the melting temperature. Mimicking
      the functional anatomy of a scallop, the SDN exhibits high cellular permeability
      and resistance to enzymatic degradation, good reversibility, and tunable response
      range. Furthermore, FRET ratiometric signal that allows the simultaneous
      recording of two emission intensities at different wavelengths can provide a
      feasible approach for precise detection, minimizing the effect of system
      fluctuations.

PMID- 29065679
TI  - Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression.
AB  - Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old
      woman as part of a health screening program, and revealed a depressed lesion
      approximately 20 mm in diameter in the lesser curvature of the mid-gastric body.
      Several biopsy specimens were collected as the lesion resembled early gastric
      cancer; however, histopathologic evaluation revealed chronic active gastritis
      with an ulcer and amorphous eosinophilic material deposition. Congo red staining
      identified amyloid proteins, and apple-green birefringence was shown using
      polarized light microscopy. Immunohistochemical staining revealed the presence of
      kappa and lambda chain-positive plasma cells. There was no evidence of underlying
      plasma cell dyscrasia or amyloid deposition in other segments of the
      gastrointestinal tract. Echocardiography and computed tomography of the chest,
      abdomen, and pelvis did not show any significant findings. Thus, the patient was
      diagnosed with localized gastric amyloidosis with kappa and lambda light chain
      coexpression.

PMID- 29065682
TI  - Ultrasensitive Detection of Methylmercaptan Gas Using Layered Manganese Oxide
      Nanosheets with a Quartz Crystal Microbalance Sensor.
AB  - Methylmercaptan (MM) is a marker of periodontal disease; however, the required
      sensitivity for MM is parts per billion, which has been challenging to realize
      with a simple sensor. Here, we report the capability to detect MM at
      concentrations as low as 20 ppb using layered manganese oxide nanosheets with a
      quartz crystal microbalance sensor. The sensing capabilities of the manganese
      oxide nanosheets are promoted by adsorbed water present on and between the
      nanosheets. The strong adsorption of MM to the sensor, which is necessary for the
      high sensitivity, leads to significant hysteresis in the response on cycling due
      to irreversible adsorption. However, the sensor can be readily reset by heating
      to 80  degrees C, which leads to highly reproducible response to MM vapor at low
      concentrations. A key aspect of this sensor design is the high selectivity toward
      MM in comparison to other compounds such as ethanol, ammonia, acetaldehyde,
      acetic acid, toluene, and pyridine. This layered nanosheets design for high
      sensitivity sensors, demonstrated here for dilute MM, holds significant promise
      for addressing needs to identify sulfur compounds associated for environmental
      protection and medical diagnostics.

PMID- 29065681
TI  - Direct Analysis of Biofluids by Mass Spectrometry with Microfluidic Voltage
      Assisted Liquid Desorption Electrospray Ionization.
AB  - Signal suppression by sample matrix in direct electrospray ionization-mass
      spectrometric (ESI-MS) analysis hampers its clinical and biomedical applications.
      We report herein the development of a microfluidic voltage-assisted liquid
      desorption electrospray ionization (VAL-DESI) source to overcome this limitation.
      Liquid DESI is achieved for the first time in a microfluidic format. Direct
      analysis of urine, serum, and cell lysate samples by using the proposed
      microfluidic VAL-DESI-MS/MS method to detect chemical compounds of biomedical
      interest, including nucleosides, monoamines, amino acids, and peptides is
      demonstrated. Analyzing a set of urine samples spiked with dihydroxyphenylalanine
      (DOPA) showed that the assay had a linear calibration curve with r2 value of
      0.997 and a limit of detection of 0.055 MUM DOPA. The method was applied to
      simultaneous quantification of nucleosides, that is, cytidine, adenosine,
      uridine, thymidine, and guanosine in cell lysates using 8-bromoadenosine as
      internal standard. Adenosine was found most abundant at 26.5 +/- 0.57 nmol/106
      cells, while thymidine was least at 3.1 +/- 0.31 nmol/106 cells. Interestingly,
      the ratio of adenosine to deoxyadenosine varied significantly from human red
      blood cells (1.07 +/- 0.06) to cancerous cells, including lymphoblast TK6 (0.52
      +/- 0.02), skin melanoma C32 (0.82 +/- 0.04), and promyelocytic leukemia NB4
      cells (0.38 +/- 0.06). These results suggest that the VAL-DESI-MS/MS technique
      has a good potential in direct analysis of biofluids. Further, because of the
      simplicity in its design and operation, the proposed microfluidic liquid DESI
      source can be fabricated as a disposable device for point-of-care measurements.

PMID- 29065683
TI  - Shock Tube and Laser Absorption Study of CH2O Oxidation via Simultaneous
      Measurements of OH and CO.
AB  - The oxidation of Ar-diluted stoichiometric CH2O-O2 mixtures was studied behind
      reflected shock waves over temperatures of 1332-1685 K, at pressures of about 1.5
      atm and initial CH2O mole fractions of 500, 1500, and 5000 ppm. Quantitative and
      time-resolved concentration histories of OH and CO (at both v" = 0 and v" = 1)
      were measured by narrow-linewidth laser absorption at 306.7 and 4854 nm,
      respectively. A time delay was observed between the formation of v" = 0 and v" =
      1 states of CO, suggesting that CO was kinetically generated primarily in the
      ground state and then collisionally relaxed toward vibrational equilibrium. The
      measured CO and OH time-histories were used to evaluate the performance of four
      detailed reaction mechanisms regarding the oxidation chemistry of CH2O. Further
      analyses of these time-history data have also led to improved determination for
      the rate constants of two key reactions, namely H + O2 = O + OH (R1) and OH + CO
      = CO2 + H (R2), as follows: k1 = 8.04 * 1013 exp(-7370 K/T) cm3 mol-1 s-1, k2 =
      1.90 * 1012 exp(-2760 K/T) cm3 mol-1 s-1; both expressions are valid over 1428
      1685 K and have 1sigma uncertainties of approximately +/-10%.

PMID- 29065685
TI  - Solution-Phase Conformation and Dynamics of Conjugated Isoindigo-Based Donor
      Acceptor Polymer Single Chains.
AB  - Conjugated polymers are the key material in thin-film organic optoelectronic
      devices due to the versatility of these molecules combined with their
      semiconducting properties. A molecular-scale understanding of conjugated polymers
      is important to the optimization of the thin-film morphology. We examine the
      solution-phase behavior of conjugated isoindigo-based donor-acceptor polymer
      single chains of various chain lengths using atomistic molecular dynamics
      simulations. Our simulations elucidate the transition from a rod-like to a coil
      like conformation from an analysis of normal modes and persistence length. In
      addition, we find another transition based on the solvent environment,
      contrasting the coil-like conformation in a good solvent with a globule-like
      conformation in a poor solvent. Overall, our results provide valuable insights
      into the transition between conformational regimes for conjugated polymers as a
      function of both the chain length and the solvent environment, which will help to
      accurately parametrize higher level models.

PMID- 29065684
TI  - Quantifying O3 Impacts in Urban Areas Due to Wildfires Using a Generalized
      Additive Model.
AB  - Wildfires emit O3 precursors but there are large variations in emissions, plume
      heights, and photochemical processing. These factors make it challenging to model
      O3 production from wildfires using Eulerian models. Here we describe a
      statistical approach to characterize the maximum daily 8-h average O3 (MDA8) for
      8 cities in the U.S. for typical, nonfire, conditions. The statistical model
      represents between 35% and 81% of the variance in MDA8 for each city. We then
      examine the residual from the model under conditions with elevated particulate
      matter (PM) and satellite observed smoke ("smoke days"). For these days, the
      residuals are elevated by an average of 3-8 ppb (MDA8) compared to nonsmoke days.
      We found that while smoke days are only 4.1% of all days (May-Sept) they are 19%
      of days with an MDA8 greater than 75 ppb. We also show that a published method
      that does not account for transport patterns gives rise to large overestimates in
      the amount of O3 from fires, particularly for coastal cities. Finally, we apply
      this method to a case study from August 2015, and show that the method gives
      results that are directly applicable to the EPA guidance on excluding data due to
      an uncontrollable source.

PMID- 29065686
TI  - Organocatalytic Enantioselective Michael-Acetalization-Henry Reaction Cascade of
      2-Hydroxynitrostyrene and 5-Oxohexanal for the Entry to the Hexahydro-6H
      benzo[c]chromenones with Four Consecutive Stereogenic Centers and an Approach to
      Aflatoxin Analogues.
AB  - A domino reaction with the organocatalytic enantioselective Michael-acetalization
      Henry reaction of 2-hydroxynitrostyrene and 5-oxohexanal was developed for the
      synthesis of hexahydro-6H-benzo[c]chromenones with four consecutive stereogenic
      centers and high enantioselectivity (up to >99% ee). The transformation of a
      NaBH4-reduced adduct to the aflatoxin system via the Nef-cyclization process was
      achieved by the assistant of ZnBr2.

PMID- 29065687
TI  - Nonenzymatic Sensor for Lactate Detection in Human Sweat.
AB  - For noninvasive diagnostics of hypoxia, we propose the nonenzymatic sensor based
      on screen-printed structures with the working surface modified in course of
      electropolymerization of 3-aminophenylboronic acid (3-APBA) with imprinting of
      lactate. Impedimetric sensor allows lactate detection in the range from 3 mM to
      100 mM with the detection limit of 1.5 mM; response time is 2-3 min. Sensor
      sensitivity remains unchanged within 6 months of storage unpacked in dry state at
      a room temperature, which is unachievable for enzyme based devices. Analysis of
      human sweat with poly(3-APBA) based sensor is possible due to (i) much higher
      lactate content compared to other polyols and (ii) high sensor selectivity
      (Klactateglucose < 3 * 10-2). Successful detection of lactate in human sweat by
      means of the poly(3-APBA) based sensor has been confirmed using the highly
      specific reference method based on lactate oxidase enzyme (correlation
      coefficient r > 0.9). The attractive performance characteristics of poly(3-APBA)
      based enzyme-free sensors justify their future use for noninvasive clinical
      analysis and sports medicine.

PMID- 29065688
TI  - Tandem Femto- and Nanomolar Analysis of Two Protein Biomarkers in Plasma on a
      Single Mixed Antibody Monolayer Surface Using Surface Plasmon Resonance.
AB  - The multiplexed detection of protein biomarkers in plasma present over a range of
      clinically relevant concentrations continues to be difficult for surface-based
      bioaffinity detection platforms such as surface plasmon resonance (SPR). As well
      as nonspecific adsorption, challenges include quantitative comparison between
      targets whose concentrations differ by orders of magnitude, regenerating SPR
      chips after plasma exposure, and the two- or four-channel limitation of many
      commercial SPR instruments limiting sample throughput. In this article, we
      explore an approach where two protein biomarkers alpha-1 antitrypsin (AAT) and
      Tau 381 are detected in tandem within a single SPR channel at micromolar and
      femtomolar concentrations, respectively. This was achieved by creating a mixed
      antibody (antiAAT and antiTau) monolayer on the chip surface. After the
      adsorption of AAT and/or Tau, further specificity was obtained via the adsorption
      of a DNA aptamer specific to each target. The detection range for each target was
      controlled via the relative surface density ratio of each antibody type as well
      as each aptamer concentration. Calibration measurements were performed in both
      buffer and spiked plasma with the detection of native concentrations of ~39 fM
      (Tau) and ~65 MUM (AAT) in a human plasma sample. Finally, tandem measurements of
      both targets within the same SPR signal channel were demonstrated at these very
      different concentrations.

PMID- 29065689
TI  - An Exploration of the Calcium-Binding Mode of Egg White Peptide, Asp-His-Thr-Lys
      Glu, and In Vitro Calcium Absorption Studies of Peptide-Calcium Complex.
AB  - The binding mode between the pentapeptide (DHTKE) from egg white hydrolysates and
      calcium ions was elucidated upon its structural and thermodynamics
      characteristics. The present study demonstrated that the DHTKE peptide could
      spontaneously bind calcium with a 1:1 stoichiometry, and that the calcium-binding
      site corresponded to the carboxyl oxygen, amino nitrogen, and imidazole nitrogen
      atoms of the DHTKE peptide. Moreover, the effect of the DHTKE-calcium complex on
      improving the calcium absorption was investigated in vitro using Caco-2 cells.
      Results showed that the DHTKE-calcium complex could facilitate the calcium influx
      into the cytosol and further improve calcium absorption across Caco-2 cell
      monolayers by more than 7 times when compared to calcium-free control. This study
      facilitates the understanding about the binding mechanism between peptides and
      calcium ions as well as suggests a potential application of egg white peptides as
      nutraceuticals to improve calcium absorption.

PMID- 29065691
TI  - Introduction: Bioinspired and Biomimetic Materials.

PMID- 29065690
TI  - Development of Multiple Heart-Cutting Two-Dimensional Liquid Chromatography
      Coupled to Quadrupole-Orbitrap High Resolution Mass Spectrometry for Simultaneous
      Determination of Aflatoxin B1, B2, G1, G2, and Ochratoxin A in Snus, a Smokeless
      Tobacco Product.
AB  - The combination of multiple heart-cutting two-dimensional liquid chromatography
      (MHC-LC/LC) and quadrupole-orbitrap high-resolution mass spectrometry (HRMS) for
      simultaneous determination of the aflatoxins and ochratoxin A in snus is
      presented in this work. A C18 capillary column was used as the first dimension
      (1D) to isolate the aflatoxins and ochratoxin A from the complex matrices; then,
      a 2-position/10-port high-pressure valve equipped with two 60 MUL loops was
      employed to transfer the heart-cuts of 1D-LC into a pentafluorophenyl (PFP)
      column for the second dimension (2D) separation. With the better separation of
      the MHC-LC/LC system, the sensitivity of the method was improved, which is
      essential for the trace mycotoxins analysis. Furthermore, HRMS performed in
      parallel reaction monitoring mode was employed to eliminate the interferences,
      and the sample pretreatment procedure was simplified. A new approach utilizing
      ethyl acetate with 1% formic acid/water solution was adopted to extract
      aflatoxins and ochratoxin A in snus, which provided parallel recoveries for
      aflatoxins and ochratoxin A with higher responses in comparison with the QuEChERS
      method. A dynamic range between 0.2 and 20 MUg/kg was achieved with LOQs of 0.05
      MUg/kg for aflatoxin B1, 0.1 MUg/kg for aflatoxin B2, G1, G2, and 1.0 MUg/kg for
      ochratoxin A in dry mass of product. The results revealed that the established
      method exhibited good repeatability and recovery and could be used as a rapid and
      reliable approach for routine analysis of aflatoxins and ochratoxin A in snus.

PMID- 29065692
TI  - Diffusion-Ordered Nuclear Magnetic Resonance Spectroscopy (DOSY-NMR): A Novel
      Tool for Identification of Phosphorus Compounds in Soil Extracts.
AB  - Liquid-state, one-dimension 31P nuclear magnetic resonance spectroscopy (NMR) has
      greatly advanced our understanding of the composition of organic phosphorus in
      the environment. However, the correct assignment of signals is complicated by
      overlapping and shifting signals in different types of soils. We applied
      therefore for the first time diffusion-ordered spectroscopy (DOSY) to soil
      extracts, allowing us to separate phosphorus components in the second domain
      based on their translational diffusion coefficients. After successful application
      to a mixture of 14 model compounds, diffusion rates correlated closely with the
      molecular weight of the individual compound in aqueous solution (R2 = 0.97). The
      method was then applied to NaOH/EDTA extracts of a grassland soil, of which
      paramagnetic contaminations were removed with sodium sulfide following high
      velocity centrifugation (21 500g, 45 min) at 4  degrees C. Diffusion rates in
      soil extracts were again closely related to molecular weight (R2 = 0.98), varying
      from 163.9 to 923.8 Da. However, our DOSY application failed for a forest soil
      with low organic phosphorus content. Overall, DOSY did help to clearly identify
      specific NMR signals like myo- and scyllo-inositol hexakisphosphate. It thus
      provides a more confident signal assignment than 1D 31P NMR, although currently
      the ubiquitous use of this novel methodology is still limited to soils with high
      organic phosphorus content.

PMID- 29065695
TI  - Photothermal Determination of Absorption and Scattering Spectra of Silver
      Nanoparticles.
AB  - This work reports on photothermal lens spectra of silver nanoparticles of
      different dimensions in the spectral region of 370-730 nm performed using an arc
      lamp-based photothermal spectrophotometer. We show that the photothermal and
      extinction cross-section spectra of the samples are similar for nanoparticles of
      reduced dimensions where scattering effects are small. The results differ
      substantially for nanoparticles of a diameter larger than 30 nm for which
      scattering becomes relevant. We demonstrate that the photothermal spectrum
      corresponds to the absorption component of the particle's extinction.
      Photothermal spectra show a clear picture of the plasmonic peaks of the
      nanoparticle even in the presence of high scattering. By subtracting the
      photothermal component from the total extinction, we extract the scattering cross
      section spectra of the nanoparticles. The technique allows determination of the
      absorption and scattering components of the extinction providing a better
      understanding of the particle's optical properties. The results agree well with
      the Mie approximation, which is valid for a single spherical nanoparticle. We
      discuss and demonstrate the application of the method to characterize particles
      of arbitrary shape and dimensions.

PMID- 29065694
TI  - ICRP Publication 135: Diagnostic Reference Levels in Medical Imaging.
AB  - Abstract -: The International Commission on Radiological Protection (ICRP) first
      introduced the term 'diagnostic reference level' (DRL) in 1996 in Publication 73.
      The concept was subsequently developed further, and practical guidance was
      provided in 2001. The DRL has been proven to be an effective tool that aids in
      optimisation of protection in the medical exposure of patients for diagnostic and
      interventional procedures. However, with time, it has become evident that
      additional advice is needed. There are issues related to definitions of the terms
      used in previous guidance, determination of the values for DRLs, the appropriate
      interval for re-evaluating and updating these values, appropriate use of DRLs in
      clinical practice, methods for practical application of DRLs, and application of
      the DRL concept to newer imaging technologies. This publication is intended as a
      further source of information and guidance on these issues. Some terminology has
      been clarified. In addition, this publication recommends quantities for use as
      DRLs for various imaging modalities, and provides information on the use of DRLs
      for interventional procedures and in paediatric imaging. It suggests
      modifications in the conduct of DRL surveys that take advantage of automated
      reporting of radiation-dose-related quantities, and highlights the importance of
      including information on DRLs in training programmes for healthcare workers. The
      target audience for this publication is national, regional, and local
      authorities; professional societies; and facilities that use ionising radiation
      for medical purposes, and responsible staff within these facilities. A full set
      of the Commission's recommendations is provided.

PMID- 29065696
TI  - Enhanced White Matter Integrity in Corpus Callosum of Long-Term Brahmakumaris
      Rajayoga Meditators.
AB  - Meditation has a versatile nature to affect cognitive functioning of human brain.
      Recent researches demonstrated its effects on white matter (WM) properties of
      human brain. In this research, we aim to investigate WM microstructure of corpus
      callosum (CC) in long-term meditators (LTMs) of rajayoga meditation using
      diffusion tensor imaging. For this cross-sectional analysis, 22 LTMs and 17
      control participants of age ranging from 30 to 50 years were recruited. Results
      show high fractional anisotropy values with low mean diffusivity in whole as well
      as different segments of CC in the LTM group. Also the experience of meditation
      was correlated with WM properties of CC tracts. Findings may suggest rajayoga
      meditation to bring potential changes in microstructure of CC segments. Further
      studies are suggested in clinical population to check its validity and efficacy
      against disorders involving agenesis of WM.

PMID- 29065698
TI  - Dysregulation of serum microRNA-574-3p and its clinical significance in
      hepatocellular carcinoma.
AB  - Objectives To explore microRNA-574-3p expression in serum of patients with
      hepatocellular carcinoma and investigate correlations between serum microRNA-574
      3p expression and the development and prognosis of hepatocellular carcinoma.
      Design and methods Serum samples were collected from 70 patients with primary
      hepatocellular carcinoma, 40 patients with cirrhosis and 45 healthy controls.
      Serum microRNA-574-3p expression levels were detected by real-time quantitative
      polymerase chain reaction. The linearity, specificity and reproducibility were
      evaluated. In addition, the diagnostic value of microRNA-574-3p and its
      correlations with clinicopathologic features were assessed. Results The relative
      expression of microRNA-574-3p in hepatocellular carcinoma patients, cirrhosis
      patients and healthy controls was 2.306 (1.801-3.130), 1.362 (0.994-1.665) and
      1.263 (0.765-1.723), respectively, indicating that it was significantly higher in
      hepatocellular carcinoma patients than that in the other two groups ( U = 439.5,
      514.5, both P < 0.0001) and was significantly correlated with hepatitis B virus
      DNA copies ( U = 383.0, P = 0.018). In hepatitis B virus-positive hepatocellular
      carcinoma patients, the relative expression of microRNA-574-3p was significantly
      correlated with hepatitis B virus DNA concentration ( r = 0.348, P = 0.022).
      Compared with healthy control group, AUCROC of serum microRNA-574-3p in
      hepatocellular carcinoma group was 0.837 with 95% CI: 0.763-0.910. Combining
      microRNA-574-3p, AFU and alpha-fetoprotein together, the sensitivity was highest
      compared with other markers alone or combined. Conclusions The relative
      expression of serum microRNA-574-3p in hepatocellular carcinoma patients was
      significantly higher than that in cirrhosis patients and healthy controls, and it
      may be an important biomarker in the auxiliary diagnosis of hepatocellular
      carcinoma.

PMID- 29065697
TI  - Altered Functional Connectivity Between Precuneus and Motor Systems in
      Parkinson's Disease Patients.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder that affects motor
      skills and cognition. As brain structure and function are compromised, functional
      magnetic resonance imaging (fMRI) can be a helpful tool to further investigate
      how intrinsic connectivity is impaired on the disease. The precuneus and medial
      prefrontal cortex (mPFC) are hub regions involved on the default mode network
      (DMN), a system that is active during rest and related to cognitive processes. We
      hypothesized that PD patients would present a decrease in functional connectivity
      among these two regions and the rest of the brain. Our goal was to identify
      regions in which functional connectivity to precuneus and mPFC was altered in PD.
      This study was based on resting-state fMRI data from 37 healthy subjects and 55
      PD patients. Precuneus and mPFC were selected as seed regions in a whole brain
      functional connectivity mapping. As expected, we found abnormal connectivity from
      precuneus to motor system regions in PD patients, pointing toward a decreased
      connectivity in the disease. No significant group effects were found for the
      mPFC. Our findings suggest that internetwork connectivity from DMN to motor
      system is impaired in PD.

PMID- 29065699
TI  - Performance of autotaxin as a serum marker for liver fibrosis.
AB  - Background Because autotaxin reportedly has a better performance than hyaluronic
      acid as a marker for liver fibrosis for the prediction of cirrhosis caused by
      hepatitis C, we aimed to further evaluate the role of autotaxin in liver fibrosis
      of other aetiologies. Methods Autotaxin antigen was measured in serum samples
      from 108 patients with chronic hepatitis B and 128 patients with non-alcoholic
      fatty liver disease who had undergone a liver biopsy as well as healthy subjects
      and patients with chronic kidney disease, diabetes mellitus, rheumatoid arthritis
      and cardiac dysfunction. Results When evaluated using receiver operator
      characteristics curves, the performance of autotaxin for the prediction of
      significant fibrosis (F2-F4) in chronic hepatitis B patients was better than that
      of hyaluronic acid or type IV collagen 7S. In non-alcoholic fatty liver disease
      patients, however, the performance of autotaxin for the prediction of significant
      fibrosis was poorer than that of hyaluronic acid or type IV collagen 7S. The
      increase in the serum autotaxin concentrations was less notable than that of
      hyaluronic acid or type IV collagen in patients with chronic kidney disease,
      diabetes mellitus, rheumatoid arthritis or cardiac dysfunction. Food intake did
      not affect the serum autotaxin concentrations. Conclusions Autotaxin is useful as
      a serum marker for liver fibrosis caused by not only chronic viral hepatitis C
      but also by hepatitis B, although it was less useful in patients with non
      alcoholic fatty liver disease. The increase in serum autotaxin concentrations is
      fairly specific for liver fibrosis, and the serum autotaxin concentrations can be
      analysed without consideration of food intake before blood collection.

PMID- 29065701
TI  - Postpartum hemorrhage from non-uterine arteries: clinical importance of their
      detection and the results of selective embolization.
AB  - Background Identification of the source of postpartum hemorrhage (PPH) is
      important for embolization because PPH frequently originates from non-uterine
      arteries. Purpose To evaluate the clinical importance of identifying the non
      uterine arteries causing the PPH and the results of their selective embolization.
      Material and Methods This retrospective study enrolled 59 patients who underwent
      embolization for PPH from June 2009 to July 2016. Angiographic findings and
      medical records were reviewed to determine whether non-uterine arteries
      contributed to PPH. Arteries showing extravasation or hypertrophy accompanying
      uterine hypervascular staining were regarded as sources of the PPH. The results
      of their embolization were analyzed. Results Of 59 patients, 19 (32.2%) underwent
      embolization of non-uterine arteries. These arteries were ovarian (n = 7),
      vaginal (n = 5), round ligament (n = 5), inferior epigastric (n = 3), cervical (n
      = 2), internal pudendal (n = 2), vesical (n = 1), and rectal (n = 1) arteries.
      The embolic materials used included n-butyl cyanoacrylate (n = 9), gelatin sponge
      particles (n = 8), gelatin sponge particles with microcoils (n = 1), and
      polyvinyl alcohol particles (n = 1). In 13 patients, bilateral uterine arterial
      embolization was performed. Re-embolization was performed in two patients with
      persistent bleeding. Hemostasis was achieved in 17 (89.5%) patients. Two patients
      underwent immediate hysterectomy due to persistent bleeding. One patient
      experienced a major complication due to pelvic organ ischemia. One patient
      underwent delayed hysterectomy for uterine infarction four months later.
      Conclusion Non-uterine arteries are major sources of PPH. Detection and selective
      embolization are important for successful hemostasis.

PMID- 29065702
TI  - Decreased background parenchymal enhancement of the contralateral breast after
      two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2
      positive breast cancer.
AB  - Background Several recent studies have focused on the association between
      background parenchymal enhancement (BPE) and tumor response to neoadjuvant
      chemotherapy (NAC), but early prediction of tumor response based on BPE has yet
      not been investigated. Purpose To retrospectively investigate whether changes in
      the BPE of the contralateral breast following NAC could help predict tumor
      response in early stage HER2-positive breast cancer. Material and Methods Data
      from 71 patients who were diagnosed with unilateral HER2 positive breast cancer
      and then underwent NAC with trastuzumab before surgery were analyzed
      retrospectively. Two experienced radiologists independently categorized the
      patients' levels of BPE of the contralateral breast into four categories (1 =
      minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second
      cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete
      response (pCR) and 37 patients had residual disease (non-pCR). The association
      between BPE and histopathologic tumor response was analyzed. Result The level of
      BPE was higher in premenopausal than post-menopausal women both at baseline and
      after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P <
      0.001) was observed after the second NAC cycle; however, a more obvious decrease
      in BPE was identified in premenopausal relative to post-menopausal women ( P =
      0.041). No significant association was identified between pCR and baseline BPE (
      P = 0.287). However, after the second NAC cycle, decreased BPE was significantly
      associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes
      in BPE may serve as an additional imaging biomarker of treatment response at an
      early stage.

PMID- 29065700
TI  - Murine Bone Marrow Mesenchymal Stromal Cells Respond Efficiently to Oxidative
      Stress Despite the Low Level of Heme Oxygenases 1 and 2.
AB  - AIMS: Mesenchymal stromal cells (MSCs) are heterogeneous cells from adult tissues
      that are able to differentiate in vitro into adipocytes, osteoblasts, or
      chondrocytes. Such cells are widely studied in regenerative medicine. However,
      the success of cellular therapy depends on the cell survival. Heme oxygenase-1
      (HO-1, encoded by the Hmox1 gene), an enzyme converting heme to biliverdin,
      carbon monoxide, and Fe2+, is cytoprotective and can affect stem cell
      performance. Therefore, our study aimed at assessing whether Hmox1 is critical
      for survival and functions of murine bone marrow MSCs. RESULTS: Both MSC Hmox1+/+
      and Hmox1-/- showed similar phenotype, differentiation capacities, and production
      of cytokines or growth factors. Hmox1+/+ and Hmox1-/- cells showed similar
      survival in response to 50 MUmol/L hemin even in increased glucose concentration,
      conditions that were unfavorable for Hmox1-/- bone marrow-derived proangiogenic
      cells (BDMC). Hmox1+/+ MSCs but not fibroblasts retained low ROS levels even
      after prolonged incubation with 50 MUmol/L hemin, although both cell types have a
      comparable Hmox1 expression and similarly increase its levels in response to
      hemin. MSCs Hmox1-/- treated with hemin efficiently induced expression of a vast
      panel of antioxidant genes, especially enzymes of the glutathione pathway.
      Innovation and Conclusion: Hmox1 overexpression is a popular strategy to enhance
      viability and performance of MSCs after the transplantation. However, murine MSCs
      Hmox1-/- do not differ from wild-type MSCs in phenotype and functions. MSC Hmox1
      /- show better resistance to hemin than fibroblasts and BDMCs and rapidly react
      to the stress by upregulation of quintessential genes in antioxidant response.
      Antioxid. Redox Signal. 00, 000-000.

PMID- 29065703
TI  - Safety and effectiveness of transarterial embolization for splenic artery
      hemorrhage in patients undergoing radical gastrectomy.
AB  - Background Perigastric lymph nodes are dissected during gastrectomy, potentially
      resulting in life-threatening postoperative bleeding. Purpose To evaluate the
      safety and effectiveness of transarterial embolization (TAE) for bleeding from
      the splenic artery in patients who underwent gastrectomy. Material and Methods
      Between January 2004 and December 2016, 14,523 patients underwent gastrectomy at
      our institution, and ten patients (nine men; mean age = 64.7 years; age range =
      51-80 years) underwent TAE for postoperative bleeding from the splenic artery.
      The location of bleeding was classified as either: (i) the main splenic artery
      (MSA) or (ii) the parenchymal splenic artery (PSA). The clinical outcomes of TAE
      were explored. Results Bleeding occurred at a median of 13.5 days (range = 4-34
      days) after gastrectomy. The onset of bleeding was late in all patients and
      clinically manifested as abdominal bleeding in seven patients and luminal
      bleeding in three patients. Technical and clinical success rates were 100% and
      70%, respectively. The three major complications occurred only in patients with
      MSA bleeding, resulting in two 30-day mortality cases and one splenic abscess
      with fistula formation to the jejunum. The causes of death were infarctions in
      the spleen and/or remnant stomach and sepsis. Conclusion TAE seems to be
      effective in stabilizing patients with bleeding from the splenic artery.
      Moreover, TAE with curative intent may be performed for bleeding from the PSA;
      however, further resection of the remnant stomach and/or spleen seems to be
      required to avoid sepsis and mortality in case of bleeding from the MSA.

PMID- 29065704
TI  - Diffusion-weighted MRI combined with susceptibility-weighted MRI: added
      diagnostic value for four common lateral ventricular tumors.
AB  - Background Diffusion-weighted imaging (DWI) and susceptibility-weighted imaging
      (SWI) are reliable imaging modalities for brain tumors. However, the role of DWI
      and SWI in the diagnosis of common lateral ventricular tumors has not been
      systematically evaluated. Purpose To evaluate the diagnostic performance of DWI
      and SWI in common lateral ventricular tumors. Material and Methods Fifty-two
      patients with histopathologically confirmed lateral ventricular tumors were
      included in this study (18 with central neurocytomas, nine with ependymomas,
      seven with high-grade gliomas, and 18 with meningiomas). The relative minimum
      apparent diffusion coefficient (rADCmin) and relative average apparent diffusion
      coefficient (rADCave) measured by DWI and the intratumoral susceptibility signal
      intensity (ITSS) of hemorrhage acquired by SWI were calculated. These
      quantitative parameters were evaluated using the Mann-Whitney U test, receiver
      operating characteristic curve, and logistic regression analyses. Results The
      rADCmin and rADCave ratios of central neurocytomas were significantly lower than
      those of the other neoplasms. The rADCmin and rADCave ratios of ependymomas and
      the rADCave ratio of high-grade gliomas were significantly higher than those of
      meningiomas. The ITSS score of meningiomas was significantly lower than those of
      the other tumors, while the score of central neurocytomas was obviously lower
      than those of ependymomas and high-grade gliomas. The combination of the rADC
      ratio with the ITSS showed no significant difference, except in discriminating
      between meningiomas and high-grade glioma-ependymomas. Conclusion The rADC ratios
      and ITSS may be useful for differentiating common lateral ventricular tumors. The
      diagnostic performance may be improved with the use of the rADC ratios and ITSS
      scores.

PMID- 29065705
TI  - Effects of a probiotic (SLAB51TM) on clinical and histologic variables and
      microbiota of cats with chronic constipation/megacolon: a pilot study.
AB  - Chronic constipation (CC) and idiopathic megacolon (IMC) occur frequently in
      cats. The aim of the study was to investigate the effects of a multi-strain
      probiotic (SLAB51TM) in constipated cats (n=7) and in patients with megacolon and
      constipation (n=3). Ten pet cats with a diagnosis of chronic constipation, non
      responsive to medical management received orally 2*1011 bacteria daily for 90
      days. For microbiota analysis, selected bacterial groups were analysed by qPCR.
      Histological samples in megacolons were evaluated for interstitial cells of Cajal
      (ICC), enteric neurons, and neuronal apoptosis. Biopsies were compared at
      baseline (T0) and after the end of treatment (T1), and with those obtained from
      healthy control tissues (archived material from five healthy cats). Constipated
      cats displayed significantly lower ICC, and cats with idiopathic megacolon had
      significantly more apoptotic enteric neurons than controls. After treatment with
      SLAB51TM, significant decreases were observed for feline chronic enteropathy
      activity index (FCEAI) (P=0.006), faecal consistency score, and mucosal histology
      scores (P<0.001). In contrast, a significant increase of ICC was observed after
      probiotic therapy. Lactobacillus spp. and Bacteroidetes were increased
      significantly after treatment (comparing constipated cats before and after
      treatment, and control healthy cats to constipated cats after treatment), but no
      other differences in microbiota were found between healthy controls and
      constipated cats. Treatment with SLAB51TM in cats with chronic constipation and
      idiopathic megacolon showed significant clinical improvement after treatment, and
      histological parameters suggest a potential anti-inflammatory effect of SLAB51TM,
      associated with a reduction of mucosal infiltration, and restoration of the
      number of interstitial cells of Cajal.

PMID- 29065706
TI  - Bacteriocin biosynthesis contributes to the anti-inflammatory capacities of
      probiotic Lactobacillus plantarum.
AB  - Plantaricin EF (PlnEF) is a class IIb bacteriocin produced by Lactobacillus
      plantarum. We compared L. plantarum NCIMB8826 and LM0419, a plnEFI deletion
      mutant of that strain lacking plnEF and the gene for the cognate immunity protein
      plnI, in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced mouse model of acute
      inflammatory bowel disease. Mice fed either L. plantarum NCIMB8826 or LM0419 were
      not protected against TNBS according to either disease activity or histology
      (Ameho) scores. Mice consuming NCIMB8826 exhibited intermediate (non-significant)
      levels of colonic tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL
      6) that ranged between the TNBS-treated animals and healthy controls. By
      comparison, TNF-alpha and IL-6 quantities were elevated in mice given L.
      plantarum LM0419 and equivalent to mice given TNBS alone. Both strains survived
      digestive tract transit in equal numbers and did not result in global changes to
      the bacterial composition in the intestine according to 16S rRNA gene sequencing
      either prior to or after TNBS administration. Examination of intestinal taxa
      showed that mice consuming wild-type L. plantarum, but not LM0419 contained lower
      proportions of Mucispirillum (Deferribacteres phylum) in the faeces prior to TNBS
      administration and Parabacteroides (Bacteroidetes phylum) in the caecum after
      disease induction. Parabacteroides also positively correlated with disease
      activity and histology scores. These findings suggest a role for PlnEFI
      production by L. plantarum in benefiting digestive tract health.

PMID- 29065708
TI  - Intracellular GSH of Streptococcus thermophilus shows anti-oxidative activity
      against low-density lipoprotein oxidation in vitro and in a hyperlipidaemic
      hamster model.
AB  - Streptococcus thermophilus YIT 2001 (ST-1), a lactic acid bacterial strain, was
      shown to have inhibitory effects on the oxidation of low-density lipoprotein
      (LDL) and the development of aortic fatty lesions in an animal model, and lower
      the serum levels of malondialdehyde-modified LDL, an oxidative modification
      product of LDL, in a clinical trial. This study aimed to identify the
      intracellular active component of ST-1 associated with anti-oxidative activity
      against LDL oxidation. High-performance liquid chromatography-electrospray
      ionisation mass spectrometry analysis after fractionation of the cellular extract
      by reversed-phase chromatography demonstrated that the active fraction contained
      reduced glutathione (GSH). GSH showed anti-oxidative activity in a dose-dependent
      manner, while this activity disappeared following thiol derivatisation. ST-1 had
      the strongest anti-oxidative activity against LDL oxidation and the highest level
      of intracellular GSH among five strains of S. thermophilus. In addition, the anti
      oxidative activity of ST-1 after thiol derivatisation decreased by about half,
      which was similar to that of three other strains containing poor or no
      intracellular GSH or thiol components. Moreover, anti-oxidative activity against
      LDL oxidation was observed in hyperlipidaemic hamsters fed with high GSH ST-1
      cells but not in those given low GSH cells. These findings suggest that
      intracellular GSH in ST-1 may provide beneficial effects via anti-oxidative
      activity against LDL oxidation and excess oxidative stress in the blood.

PMID- 29065707
TI  - Bifidobacterium longum BB536 alleviated upper respiratory illnesses and modulated
      gut microbiota profiles in Malaysian pre-school children.
AB  - This 10-months randomised, double-blind, parallel and placebo-controlled study
      evaluated the effects of Bifidobacterium longum BB536 on diarrhoea and/or upper
      respiratory illnesses in 520 healthy Malaysian pre-school children aged 2-6 years
      old. The subjects randomly received a one-gram sachet containing either BB536
      (5*109 cfu) or placebo daily. Data analysis was performed on 219 subjects who
      fully complied over 10-months (placebo n=110, BB536 n=109). While BB536 did not
      exert significant effects against diarrhoea in children, Poisson regression with
      generalised estimating equations model indicated significant intergroup
      difference in the mean number of times of respiratory illnesses over 10 months.
      The duration of sore throat was reduced by 46% (P=0.018), with marginal reduction
      for duration of fever (reduced by 27%, P=0.084), runny nose (reduced by 15%,
      P=0.087) and cough (reduced by 16%, P=0.087) as compared to the placebo.
      Principal coordinate analysis at genus level of the gut microbiota revealed
      significant differences between 0 and 10 months in the BB536 group (P<0.01) but
      not in placebo group (P>0.05). The abundance of the genus Faecalibacterium which
      is associated with anti-inflammatory and immuno-modulatory properties was
      significantly higher in the BB536 group (P<0.05) compared to the placebo group.
      Altogether, our present study illustrated the potential protective effects of
      BB536 against upper respiratory illnesses in pre-school Malaysian children, with
      gut microbiota modulating properties.

PMID- 29065709
TI  - Direct effects of fermented cow's milk product with Lactobacillus paracasei CBA
      L74 on human enterocytes.
AB  - Cow's milk fermented with Lactobacillus paracasei CBA L74 (FM-CBAL74) exerts a
      preventive effect against infectious diseases in children. We evaluated if this
      effect is at least in part related to a direct modulation of non-immune and
      immune defence mechanisms in human enterocytes. Human enterocytes (Caco-2) were
      stimulated for 48 h with FM-CBAL74 at different concentrations. Cell growth was
      assessed by colorimetric assay; cell differentiation (assessed by lactase
      expression), tight junction proteins (zonula occludens1 and occludin), mucin 2,
      and toll-like receptor (TRL) pathways were analysed by real-time PCR; innate
      immunity peptide synthesis, beta-defensin-2 (HBD-2) and cathelicidin (LL-37) were
      evaluated by ELISA. Mucus layer thickness was analysed by histochemistry. FMCBA
      L74 stimulated cell growth and differentiation, tight junction proteins and mucin
      2 expression, and mucus layer thickness in a dose-dependent fashion. A
      significant stimulation of HBD-2 and LL-37 synthesis, associated with a
      modulation of TLR pathway, was also observed. FM-CBAL74 regulates non-immune and
      immune defence mechanisms through a direct interaction with the enterocytes.
      These effects could be involved in the preventive action against infectious
      diseases demonstrated by this fermented product in children.

PMID- 29065710
TI  - Effect of a yoghurt drink containing Lactobacillus strains on bacterial vaginosis
      in women - a double-blind, randomised, controlled clinical pilot trial.
AB  - Bacterial vaginosis (BV) is characterised by a depletion of lactobacilli in
      favour of an overgrowth of anaerobic bacteria. It is associated with increased
      risk for urogenital infections and abortion. In this study we assessed the effect
      of a yoghurt drink containing Lactobacillus strains on BV. The strains had been
      isolated from healthy pregnant women and selected for acidification capacity,
      production of H2O2, glycogen utilisation, bile salt tolerance and inhibition of
      pathogens. Using Amsel criteria BV was diagnosed in 36 women aged >=18 years with
      stable menstrual cycle or menopause. They were treated with oral metronidazole
      for 7 days (2*500 mg/d). Starting with the treatment, women consumed twice daily
      either verum or placebo during 4 weeks. Verum was 125 g yoghurt containing
      (besides Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus
      thermophilus) living strains Lactobacillus crispatus LbV 88 (DSM 22566),
      Lactobacillus gasseri LbV 150N (DSM 22583), Lactobacillus jensenii LbV 116 (DSM
      22567) and Lactobacillus rhamnosus LbV96 (DSM 22560), each 1*107 cfu/ml; placebo
      was 125 g chemically acidified milk. After 4 weeks of intervention 0 of 17 had BV
      in the verum group versus 6 of 17 in the s.a. control (0.018 in Fisher Exact
      test). Amsel score decreased during the intervention period by 4.0 (median) (4.0;
      3.0) (25th; 75th percentile) in the verum group compared to 2.0 (4.0; 0.0) in the
      control group (P=0.038 in Mann-Whitney test). Discharge and odour (Amsel criteria
      2+3) also decreased by 2.0 (2.0; 1.0) in the verum compared to 1.0 (2.0; 0.0) in
      the control group (P=0.01) and differed after 4 weeks intervention between the
      groups 0.0 (0.0; 0.0) versus 1.0 (0.0; 2.0) (P=0.001). Nugent score decreased
      during the intervention period by 5.5 (7.0;2.3) in the verum compared to 3.0
      (6.0;0.5) in the control group (P=0.158). Additional intake of yoghurt containing
      these probiotic strains improved the recovery rate and symptoms of BV and tended
      to improve the vaginal microbial pattern.

PMID- 29065711
TI  - Vascular Adhesion Protein-1: A Cell Surface Amine Oxidase in Translation.
AB  - SIGNIFICANCE: Vascular adhesion protein-1 (VAP-1) is an ectoenzyme that oxidates
      primary amines in a reaction producing also hydrogen peroxide. VAP-1 on the blood
      vessel endothelium regulates leukocyte extravasation from the blood into tissues
      under physiological and pathological conditions. Recent Advances: Inhibition of
      VAP-1 by neutralizing antibodies and by several novel small-molecule enzyme
      inhibitors interferes with leukocyte trafficking and alleviates inflammation in
      many experimental models. Targeting of VAP-1 also shows beneficial effects in
      several other diseases, such as ischemia/reperfusion, fibrosis, and cancer.
      Moreover, soluble VAP-1 levels may serve as a new prognostic biomarker in
      selected diseases. CRITICAL ISSUES: Understanding the contribution of the enzyme
      activity-independent and enzyme activity-dependent functions, which often appear
      to be mediated by the hydrogen peroxide production, in the VAP-1 biology will be
      crucial. Similarly, there is a pressing need to understand which of the VAP-1
      functions are regulated through the modulation of leukocyte trafficking, and what
      is the role of VAP-1 synthesized in adipose and smooth muscle cells. FUTURE
      DIRECTIONS: The specificity and selectivity of new VAP-1 inhibitors, and their
      value in animal models under therapeutic settings need to be addressed. Results
      from several programs studying the therapeutic potential of VAP-1 inhibition,
      which now are in clinical trials, will reveal the relevance of this amine oxidase
      in humans. Antioxid. Redox Signal. 00, 000-000.

PMID- 29065714
TI  - The Art of Health Promotion: Linking research to practice.

PMID- 29065716
TI  - Incentives and Big E Engagement.
AB  - The kind of engagement industrial psychologists have shown can produce optimal
      performance relates more to a state of mind than to increasing participation in
      programs or motivating a workforce with financial incentives. In the context of
      quality improvement methodologies, the health promotion profession has yet to
      discover when, where and how large financial incentives should be and how they
      best fit in our processes. That is, there is no "standard work" for the use of
      extrinsic motivators. Yet, to argue against incentives given evidence to date has
      more to do with polemics than science.

PMID- 29065717
TI  - A dangerous chase: severe neurocognitive impairment and death following smoked
      heroin.

PMID- 29065712
TI  - Comparison of Whole Body SOD1 Knockout with Muscle-Specific SOD1 Knockout Mice
      Reveals a Role for Nerve Redox Signaling in Regulation of Degenerative Pathways
      in Skeletal Muscle.
AB  - AIMS: Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice
      (Sod1-/-) leads to accelerated age-related muscle loss and weakness, but specific
      deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice)
      resulted in only mild muscle functional deficits and failed to recapitulate the
      loss of mass and function observed in Sod1-/- mice. To dissect any underlying
      cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1
      /- mice, we characterized neuromuscular changes in the Sod1-/- model compared
      with mSod1KO mice and examined degenerative molecular mechanisms and pathways in
      peripheral nerve and skeletal muscle. RESULTS: In contrast to mSod1KO mice,
      myofiber atrophy in Sod1-/- mice was associated with increased muscle oxidative
      damage, neuromuscular junction degeneration, denervation, nerve demyelination,
      and upregulation of proteins involved in maintenance of myelin sheaths. Proteomic
      analyses confirmed increased proteasomal activity and adaptive stress responses
      in muscle of Sod1-/- mice that were absent in mSod1KO mice. Peripheral nerve from
      neither Sod1-/- nor mSod1KO mice showed increased oxidative damage or molecular
      responses to increased oxidation compared with wild type mice. Differential
      cysteine (Cys) labeling revealed a specific redox shift in the catalytic Cys
      residue of peroxiredoxin 6 (Cys47) in the peripheral nerve from Sod1-/- mice.
      Innovation and Conclusion: These findings demonstrate that neuromuscular
      integrity, redox mechanisms, and pathways are differentially altered in nerve and
      muscle of Sod1-/- and mSod1KO mice. Results support the concept that impaired
      redox signaling, rather than oxidative damage, in peripheral nerve plays a key
      role in muscle loss in Sod1-/- mice and potentially sarcopenia during aging.
      Antioxid. Redox Signal. 28, 275-295.

PMID- 29065713
TI  - Evaluating Teach One Reach One-An STI/HIV Risk-Reduction Intervention to Enhance
      Adult-Youth Communication About Sex and Reduce the Burden of HIV/STI.
AB  - PURPOSE: Parents and caregivers play an important role in sexual socialization of
      youth, often serving as the primary source of information about sex. For African
      American rural youth who experience disparate rates of HIV/sexually transmitted
      infection, improving caregiver-youth communication about sexual topics may help
      to reduce risky behaviors. This study assessed the impact of an intervention to
      improve sexual topic communication. DESIGN: A Preintervention-postintervention,
      quasi-experimental, controlled, and community-based trial. SETTING: Intervention
      was in 2 rural North Carolina counties with comparison group in 3 adjacent
      counties. SUBJECTS: Participants (n = 249) were parents, caregivers, or parental
      figures for African American youth aged 10 to 14. INTERVENTION: Twelve-session
      curriculum for participating dyads. MEASURES: Audio computer-assisted self
      interview to assess changes at 9 months from baseline in communication about
      general and sensitive sex topics and overall communication about sex. ANALYSIS:
      Multivariable models were used to examine the differences between the changes in
      mean of scores for intervention and comparison groups. RESULTS: Statistically
      significant differences in changes in mean scores for communication about general
      sex topics ( P < .0001), communication about sensitive sex topics ( P < .0001),
      and overall communication about sex ( P < .0001) existed. Differences in change
      in mean scores remained significant after adjusting baseline scores and other
      variables in the multivariate models. CONCLUSIONS: In Teach One Reach One
      intervention, adult participants reported improved communication about sex, an
      important element to support risk reduction among youth in high-prevalence areas.

PMID- 29065718
TI  - Maxillofacial prostheses challenges in resource constrained regions.
AB  - BACKGROUND: This study reviewed the current state of maxillofacial rehabilitation
      in resource-limited nations. METHOD: A rigorous literature review was undertaken
      using several technical and clinical databases using a variety of key words
      pertinent to maxillofacial prosthetic rehabilitation and resource-limited areas.
      In addition, interviews were conducted with researchers, clinicians and
      prosthetists that had direct experience of volunteering or working in resource
      limited countries. RESULTS: Results from the review and interviews suggest
      rehabilitating patients in resource-limited countries remains challenging and
      efforts to improve the situation requires a multifactorial approach. CONCLUSIONS:
      In conclusion, public health awareness programmes to reduce the causation of
      injuries and bespoke maxillofacial prosthetics training programmes to suit these
      countries, as opposed to attempting to replicate Western training programmes. It
      is also possible that usage of locally sourced and cheaper materials and the use
      of low-cost technologies could greatly improve maxillofacial rehabilitation
      efforts in these localities. Implications for Rehabilitation More information and
      support needs to be provided to maxillofacial defect/injuries patients and to
      their families or guardians in a culturally sensitive manner by governments. The
      health needs, economic and psychological needs of the patients need to be taken
      into account during the rehabilitation process by clinicians and healthcare
      organizations. The possibility of developing training programs to suit these
      resource limited countries and not necessarily follow conventional fabrication
      methods must be looked into further by educational entities.

PMID- 29065719
TI  - Inter-rater reliability, standard error of measurement and minimal detectable
      change of the 12-item WHODAS 2.0 and four performance tests in institutionalized
      ambulatory older adults.
AB  - PURPOSE: Self-reported and performance-based instruments are both necessary for a
      comprehensive view of the functioning of institutionalized older adults. Our aim
      was to assess the reliability and measurement error of the 12-item World Health
      Organization Disability assessment Schedule and compare these indexes against
      performance-based tests. MATERIALS AND METHODS: One hundred participants from
      Nursing Homes and Day Care Centers were assessed twice (two days to one week
      apart) by two independent assessors. Reliability and measurement error indexes
      were calculated. RESULTS: Reliability of the World Health Organization Disability
      assessment Schedule total score, and of three performance tests was appropriate
      for individual comparisons (ICC >= 0.92). Reliability for the five times seat to
      stand test was appropriate for group comparisons only (ICC = 0.84). The high
      measurement error of the timed up and go test (SEM = 4.25; MDC = 11.78) and of
      the five times seat to stand test (SEM = 3.47; MDC = 9.62) and the number of
      participants unable to perform them (TUG: n = 11; FTSST: n = 41) suggest that
      these tests are less suitable to monitor individual changes. CONCLUSIONS: The 12
      item World Health Organization Disability Assessment Schedule total score, the
      gait speed and hand grip tests could be used to monitor changes at both the
      individual and group level in a population with decreased functioning.
      Implications for Rehabilitation The 12-item World Health Organization Disability
      assessment Schedule, could be used to monitor changes in perceived functioning
      both at the individual and group level in institutionalized ambulatory older
      adults. The gait speed and hand grip tests could be used to monitor changes in
      performance both at the individual and group level in institutionalized
      ambulatory older adults' functioning. The utility of the time up and go and of
      the five times seat to stand test might be of limited value when aiming to
      monitor changes in institutionalized older adults' functioning.

PMID- 29065720
TI  - Identifying insulin treatment responders with a composite measure: beyond Hba1c <
      7% in patients with type 2 diabetes.
AB  - OBJECTIVES: Many insulin-treated patients with type 2 diabetes (T2D) do not reach
      hemoglobin A1c (HbA1c) < 7%, but have clinically relevant HbA1c reductions. Using
      an integrated database (IDB) of 53 insulin lispro clinical trials and a real
      world evidence (RWE) database of T2D patients initiating insulin therapy, an
      expanded HbA1c measure was used to identify responders to insulin therapy.
      METHODS: Analysis included 4,908 patients (IDB) and 1,134 patients (RWE) with T2D
      treated with any insulin regimen with a baseline and >=1 post-baseline HbA1c.
      Responders were defined as patients with endpoint HbA1c < 7% (cut point [CP])
      and/or either >=1% absolute (ABS) decrease, and/or >=10% relative (REL) decrease
      in HbA1c from baseline. The percentage of responders with CP vs ABS and
      concordance between ABS and REL were calculated. As the ABS and REL measures were
      highly correlated (94%), the ABS measure was used to compare characteristics of
      responders and non-responders by age, diabetes duration, race/ethnicity, baseline
      HbA1c, and insulin regimen at 24 weeks. RESULTS: In both databases, more
      responders were identified with ABS or REL (>62%) than CP (<41%). More ABS
      responders had a baseline HbA1c >= 9% and a shorter diabetes duration than non
      responders. Basal insulin-treated patients in the IDB had 78.2% responders at 24
      weeks, compared to 69.7% with basal/bolus or pre-mixed insulin (75.4%). Results
      were similar in the IDB and RWE. CONCLUSION: Composite HbA1c measures identified
      more patients with clinically meaningful responses to therapy than the broadly
      accepted HbA1c < 7% and may be useful in assessing clinical trials, clinical
      care, and quality measures.

PMID- 29065721
TI  - The safety of treatments used in pyoderma gangrenosum.
AB  - INTRODUCTION: Pyoderma gangrenosum (PG) is a severe ulcerating orphan dermatosis
      characterized by painful and rapidly progressive skin ulcers often associated
      with underlying inflammatory disease. Areas covered: In this article, we review
      and analyze the literature regarding treatment options for patients with PG, with
      particular attention to the efficacy and safety of therapies. Despite the
      significance of this problem, there are few studies devoted to the efficacy or
      safety of therapeutics in PG. We aim to present and evaluate existing studies and
      reports, and to make treatment recommendations based on the efficacy and safety
      data reviewed. Expert opinion: All patients with PG should be counseled on
      avoiding trauma, optimizing glycemic control, and smoking cessation. Proper local
      wound care and surveillance of superimposed infection is essential to healing.
      Control of underlying inflammatory conditions should be co-managed with
      appropriate specialists. Patients with limited disease should consider high
      potency topical steroid or topical calcineurin inhibitors. For systemic therapy,
      the best evidence supports the use of systemic steroids or cyclosporine. Biologic
      therapy should be reserved in patients as a third line therapy or in patients
      with underlying systemic inflammatory disease. There is an existing need for well
      designed studies to evaluate the efficacy and safety of therapeutics in PG.

PMID- 29065722
TI  - Perindopril arginine and amlodipine besylate for hypertension: a safety
      evaluation.
AB  - INTRODUCTION: Controlling blood pressure is a global health priority; single-pill
      antihypertensive combinations may improve adherence, persistence, and outcomes.
      Areas covered: A novel combination of perindopril arginine and amlodipine
      besylate was recently approved. A systematic review of the literature revealed
      its most common adverse effects as: peripheral edema (depending on the dose of
      amlodipine, but attenuated by perindopril), cough, dizziness and hypotension.
      Dose-dependent hyperkalemia, impairment of renal function (especially in
      renovascular hypertension), angioedema, and teratogenicity were derived from
      experience with other ACE-inhibitors. Expert opinion: Substantial clinical trial
      experience with amlodipine or perindopril suggests that these two agents
      effectively lower blood pressure, and can reduce the risk of major adverse
      cardiovascular events, as in the Anglo-Scandinavian Cardiac Outcomes Trial. The
      incidence of adverse effects reported in clinical trials is lower than expected,
      likely due to exclusion of subjects previously exposed to its components; the
      nature of open-label, uncontrolled observational studies; and difficulty in
      recognizing and measuring cough and pedal edema. This new formulation of
      perindopril arginine protects its ethyl ester, without requiring physical
      separation from amlodipine in a single tablet, and is less hygroscopic than
      perindopril erbumine. These and other attributes may make this combination an
      attractive addition to the antihypertensive armamentarium.

PMID- 29065723
TI  - Ciliary neurotrophic factor (CNTF) delivery to retina: an overview of current
      research advancements.
AB  - The intraocular administration of the ciliary neurotrophic factor (CNTF) has been
      found to attenuate the photoreceptor degeneration and preserve retinal functions
      in the animal research models of the inherited or induced retinal disease.
      Studies with the aim of CNTF transfer to the posterior segment inside the eye
      have been directed to determine the best method for its administration. An ideal
      delivery method would overcome the eye drug elimination mechanisms or barriers
      and provide the sustained release of the CNTF into retina in the safest fashion
      with the minimum harm to the quality of life. This review focuses on the present
      state of CNTF delivery to retina, also provides an overview of available
      technologies and their challenges.

PMID- 29065725
TI  - Call for human contact and support: an interview study exploring patients'
      experiences with inpatient stroke rehabilitation and their perception of nurses'
      and nurse assistants' roles and functions.
AB  - PURPOSE: To describe patients' experiences with inpatient stroke rehabilitation
      and their perception of nurses' and nurse assistants' roles and functions during
      hospitalisation. MATERIALS AND METHODS: In a qualitative study, 10 interviews
      with stroke patients were conducted, transcribed, and analysed using qualitative
      content analysis. RESULTS: The patients' experiences with inpatient stroke
      rehabilitation and their perception of nurses' and nurse assistants' roles and
      functions during hospitalisation were found to be related to one overall theme
      derived from 10 categories. As a recurring motif in the patients' interviews,
      they experienced existential thoughts, and these thoughts unquestionably affected
      their experiences within the rehabilitation unit. These thoughts enhanced their
      need for human contact, thereby affecting their relationships with and
      perceptions of the nursing staff. CONCLUSION: The findings deepen our
      understanding of how patients experience inpatient rehabilitation. The patients
      struggled with existential thoughts and concerns about the future and therefore
      called for human contact and support from the nursing staff. They perceived the
      nursing staff as mostly polite and helpful, but were unclear about the nursing
      staff's function in rehabilitation which, in the patients' perspective, equals
      physical training. Implications for Rehabilitation Nursing staff need to pay
      attention to the patients' needs, existential thoughts and concerns during
      inpatient rehabilitation. Meaningful goals for the rehabilitation of stroke
      patients are crucial, and it is vital that the patients commit to the goals.
      Patients expected polite and helpful nurses, but did not see them as therapeutic
      and active stakeholders, thus it is important that nursing staff present
      themselves as part of the interdisciplinary rehabilitation. There is a need for
      training and education of nursing staff, both pre and post graduate.

PMID- 29065724
TI  - Microcirculatory disturbances and cellular changes during progression of hepatic
      steatosis to liver tumors.
AB  - Non-alcoholic fatty liver disease is closely associated with metabolic syndrome
      and comprises a pathological spectrum of liver disease ranging from steatosis to
      steatohepatitis and can progress to fibrosis/cirrhosis and hepatocellular
      carcinoma. In 2013, a mouse model was described that mimics non-alcoholic fatty
      liver disease progression from steatohepatitis to tumors in a short time span and
      with high incidence. As microcirculatory disturbances play a crucial role in
      liver disease, the suitability of the steatosis-inflammation-tumor model for
      microcirculatory studies was assessed. Herein, we present a comprehensive view on
      morphological, microvascular, cellular, and functional aspects of non-alcoholic
      fatty liver disease progression in the steatosis-inflammation-tumor model using
      intravital microscopy, biochemical, and histological techniques. Mice develop
      steatohepatitis, mild fibrosis, and liver tumors at ages of 6, 12, and 20 weeks,
      respectively. Non-alcoholic fatty liver disease progression was accompanied by
      several general aspects of disease severity like increasing liver/body weight
      index, non-alcoholic fatty liver disease activity score, and hepatocellular
      apoptosis. Intravital microscopic analysis revealed significant changes in
      hepatic microcirculation with increasing structural alterations, elevated
      leukocyte adherence, and impaired nutritive perfusion. Non-alcoholic fatty liver
      disease was further characterized by a lower sinusoidal density with a striking
      rise at 20 weeks. The characteristic microcirculatory changes make the model a
      convenient tool for analysis of microcirculation during progression from
      steatosis to liver tumor. Impact statement Significant alterations of
      microcirculation contribute to progression of NAFLD, a chronic liver disease with
      increasing medical and socio-economic impact. Characterization of
      microcirculation in a NAFLD model reflecting all relevant stages of disease
      progression was still missing. Thus, we evaluated microcirculatory and cellular
      changes in a steatosis-inflammation-tumor model using in vivo microscopy.
      Analyses revealed increasing structural alterations, elevated leukocyte
      endothelial interaction, and impaired nutritive perfusion. Thus, this model is
      suitable for further studies investigating therapeutic approaches targeting these
      progressive microcirculatory disturbances.

PMID- 29065727
TI  - Design and fabrication of GelMA/chitosan nanoparticles composite hydrogel for
      angiogenic growth factor delivery.
AB  - The cellular microenvironment plays a crucial role in improving cell response and
      function of an engineered tissue. Scaffolds mimicking the native ECM and capable
      of releasing growth factors are great candidates for tissue engineering
      applications. Gelatin methacryloyl (GelMA) hydrogel, a photocrosslinkable
      biomaterial possessing tunable properties, has been widely used in tissue
      engineering. It has been suggested that incorporating micro/nano carriers in
      GelMA could provide a sustained release of growth factors. Specifically, chitosan
      nanoparticles can be used for growth factor delivery due to its biocompatibility,
      easy method of synthesis, and preventing the biomolecule from degradation. In
      this study, GelMA/chitosan nanoparticles composite hydrogel was developed to
      deliver an angiogenic growth factor (bFGF). The hydrogel was prepared by
      photopolymerization and its chemical and physical properties were characterized.
      Its degradation and swelling characteristics were also evaluated. The size of
      nanoparticles was evaluated and the profile of bFGF release from the hydrogel and
      its effect on the viability of fibroblast cells was studied. The results showed
      that GelMA/chitosan nanoparticles can significantly promote cell proliferation
      due to its biocompatible structure and providing a sustained profile of bFGF
      release. This hydrogel scaffold can be used for efficient delivery of bFGF in
      various applications and especially for angiogenesis.

PMID- 29065726
TI  - Saccharopolytide A, a new cyclic tetrapeptide with rare 4-hydroxy-proline
      moieties from the deep-sea derived actinomycete Saccharopolyspora cebuensis MCCC
      1A09850.
AB  - A genome mining analysis on the deep-sea derived actinomycete Saccharopolyspora
      cebuensis MCCC 1A09850 indicated its potential to produce polypeptides.
      Accordingly, a systematic chemical investigation was conducted, which resulted in
      the isolation of one new cyclic tetrapeptide (saccharopolytide A, 1) and two
      known polyketides (2, 3) along with six other miscellaneous compounds (4-9).
      Mainly by analysis of the 1D, 2D NMR and MS data, the chemical structure of
      saccharopolytide A was established as cyclo-(l-Leu-4-hydroxy-l-Pro-l-Phe-4
      hydroxy-l-Pro). All isolates were evaluated for anti-allergic and anti-tumor
      bioactivities. Indol-3-carbaldehyde (4) showed weak anti-allergic effect with
      IC50 value of 55.75 MUg/mL. And 2 showed weak anti-proliferative activity against
      Hela and H1299 tumor cell lines. Our results consolidate the potential of deep
      sea-derived microorganisms to produce structurally interesting compounds.

PMID- 29065729
TI  - Factors associated with stroke, myocardial infarction, ischemic heart disease,
      unstable angina, or mortality in patients from real world clinical practice with
      newly-diagnosed type 2 diabetes and early glycemic control.
AB  - OBJECTIVES: The objective of this study was to identify factors associated with
      stroke, myocardial infarction (MI), all-cause mortality, or a diagnosis of
      ischemic heart disease (IHD) or unstable angina (UA), among patients newly
      diagnosed with type 2 diabetes (T2DM) with no recent history of cardiovascular
      (CV) events who rapidly achieve and maintain HbA1c <=8.0%. METHODS: Data were
      obtained from the Clinical Practice Research Datalink (CPRD) from January 1990 to
      December 2012. A nested case-control design was used with Cox proportional
      hazards analysis. Cases were identified by the first occurrence of stroke, MI,
      IHD, UA, or death within 5 years after HbA1c <= 8.0% was first reached (index
      date) following T2DM diagnosis. Controls were selected using a risk-set sampling
      approach and were matched 4:1 to cases using index date, exposure time, age,
      gender, and HbA1c at index date. RESULTS: A total of 11,426 T2DM patients met the
      inclusion criteria for cases. Of these, 5,261 experienced a CV event. Stroke was
      the most frequent CV event (40%), followed by IHD (29%), MI (22%), and UA (9%).
      Mean HbA1c >=7.0% over the length of exposure (vs 6.5 to <7.0%) was associated
      with an increased risk of stroke, MI, and IHD. The use of anti-platelet
      medications at baseline was also associated with increased risk of stroke (HR =
      1.82 [CI = 1.60-2.06]), MI (HR = 1.67 [CI = 1.38-2.03]), and IHD (HR = 1.85 [CI =
      1.57-2.17]). Mean HbA1c < 6.0% was associated with increased risk of stroke (HR =
      1.29 [CI = 1.02-1.63]) and IHD (HR = 1.65 [CI = 1.25-2.19]). Use of nitrate
      medications at baseline was associated with increased risk of MI (HR = 2.83 [CI =
      2.24-3.57]), IHD (HR = 4.32 [CI = 3.57-5.22]), and UA (HR = 10.38 [CI = 7.67
      14.03]). CONCLUSIONS: Early and sustained HbA1c control between 6.5 and <7.0%
      appears to be an important modifiable factor that helps reduce CV risk in
      patients with newly-diagnosed T2DM in real-world clinical practice.

PMID- 29065728
TI  - Results of Applying Cultural Domain Analysis Techniques and Implications for the
      Design of Complementary Feeding Interventions in Northern Senegal.
AB  - BACKGROUND: Designing effective nutrition interventions for infants and young
      children requires knowledge about the population to which the intervention is
      directed, including insights into the cognitive systems and values that inform
      caregiver feeding practices. OBJECTIVE: To apply cultural domain analysis
      techniques in the context of implementation research for the purpose of
      understanding caregivers' knowledge frameworks in Northern Senegal with respect
      to infant and young child (IYC) feeding. This study was intended to inform
      decisions for interventions to improve infant and young child nutrition. METHODS:
      Modules from the Focused Ethnographic Study for Infant and Young Child Feeding
      Manual were employed in interviews with a sample of 126 key informants and
      caregivers from rural and peri-urban sites in the Saint-Louis region of northern
      Senegal. Descriptive statistics, cluster analysis, and qualitative thematic
      analysis were used to analyze the data. RESULTS: Cluster analysis showed that
      caregivers identified 6 food clusters: heavy foods, light foods, snack foods,
      foraged foods, packaged foods, and foods that are good for the body. The study
      also revealed similarities and differences between the 2 study sites in
      caregivers' knowledge frameworks. CONCLUSIONS: The demonstration of differences
      between biomedical concepts of nutrition and the knowledge frameworks of northern
      Senegalese women with regard to IYC feeding highlights the value of knowledge
      about emic perspectives of local communities to help guide decisions about
      interventions to improve nutrition.

PMID- 29065730
TI  - Fetal hydrops and the risk of severe preeclampsia.
AB  - OBJECTIVE: To assess the incidence and severity of preeclampsia in pregnancies
      complicated by fetal hydrops. METHODS: We performed a retrospective cohort study
      of singleton gestations from 2005 to 2008 in California. The primary predictor
      was fetal hydrops and the primary outcome was preeclampsia. Selected adverse
      maternal and neonatal events were assessed as secondary outcomes. Potential
      confounders examined included fetal anomalies, polyhydramnios, race/ethnicity,
      nulliparity, chronic hypertension, and gestational or pregestational diabetes
      mellitus. RESULTS: We identified 337 pregnancies complicated by fetal hydrops,
      70.0% had a concomitant fetal anomaly and 39.8% had polyhydramnios. Compared to
      the general population, hydrops was associated with an increased risk for severe
      preeclampsia (5.26 versus 0.91%, p < .001) but not mild preeclampsia (2.86 versus
      2.02%, p = .29). In multivariable analysis, fetal hydrops remained an independent
      risk factor for severe preeclampsia (as adjusted odds ratios (aOR) 3.13, 1.91
      5.14). Hydrops was also associated with increased rates of eclampsia, acute renal
      failure, pulmonary edema, postpartum hemorrhage, blood transfusion, preterm
      birth, and neonatal death. CONCLUSIONS: We find that fetal hydrops is an
      independent risk factor for severe preeclampsia. In light of serious concerns for
      maternal and neonatal health, heightened surveillance for signs and symptoms of
      severe preeclampsia is warranted in all pregnancies complicated by fetal hydrops.

PMID- 29065731
TI  - Optimising the effect of noise reduction algorithm ClearVoice in cochlear implant
      users by increasing the maximum comfort levels.
AB  - OBJECTIVE: ClearVoice is a single-microphone noise reduction algorithm in
      Advanced Bionics cochlear implant(CI) systems with the aim to improve performance
      in background noise. The present study investigated a hypothesised increased
      effect of ClearVoice if combined with a structural increase of maximum comfort
      stimulation levels (M-levels) in the CI fitting. DESIGN: We tested performance
      with ClearVoice (Medium) in four conditions, defined by combined settings of
      ClearVoice off/on and with/without 5% increase of M-levels. The main outcome
      measures were the Acceptable Noise Level (ANL) and the speech reception threshold
      in continuous background noise (SRTn). STUDY SAMPLE: Participants were 16
      experienced cochlear implant recipients with Advanced Bionics implants and a
      Naida Q70 processor. RESULTS: The ANL significantly improved by using either
      ClearVoice or an increase of M-levels. Combining both settings gave the largest
      improvement in ANL. For the SRTn, we found a small, but significant interaction
      between ClearVoice and an increase of M-levels, implying that ClearVoice improved
      speech understanding slightly, but only if combined with a 5% increase of M
      levels. CONCLUSIONS: Optimal profit from ClearVoice is obtained if combined with
      a structural 5% increase of M-levels.

PMID- 29065732
TI  - Choice of scheduled cesarean delivery versus trial of labor for advanced maternal
      age primiparous women.
AB  - OBJECTIVE: We aimed to evaluate perinatal outcomes of advanced maternal age (AMA)
      primiparous women seeking scheduled cesarean delivery (CD) versus a trial of
      labor (TOL). MATERIALS AND METHODS: This was a retrospective cohort study of
      primiparous women >=40 years of age carrying a single fetus, who delivered at a
      tertiary, university-affiliated medical center (2007-2014). We compared perinatal
      outcomes of women who chose a scheduled CD with those who chose TOL.
      Subsequently, we compared women who had successful TOL (sTOL) with those who had
      a failed TOL (fTOL). RESULTS: Out of 62 102 deliveries during the study period,
      inclusion criteria were met by 374 women. Of them, 83 (22.2%) women had a
      scheduled CD, and 291 (77.8%) had TOL. Of the TOL group, 118 women (40.5%) had
      fTOL and 173 (59.5%) had sTOL. Women in the fTOL had higher rates of 1-min Apgar
      score <7, neonatal asphyxia and adverse neonatal composite outcome compared with
      women in the sTOL group (p < .05). After adjusting for potential confounders,
      compared with sTOL, fTOL was not associated with adverse neonatal composite
      outcome. Compared with scheduled CD, fTOL was associated with an increased risk
      for adverse neonatal composite outcome (aOR 2.65, 95% CI 1.13-6.19, p = .03).
      CONCLUSION: AMA primiparous women attempting TOL have comparable outcome to those
      seeking scheduled CD, however, women with fTOL have higher rates of adverse
      neonatal outcome.

PMID- 29065733
TI  - Hepatitis B core protein as a therapeutic target.
AB  - INTRODUCTION: Chronic hepatitis B virus (HBV) infection is difficult to cure, due
      to the presence of covalently-closed-circular DNA and virus-mediated blunting of
      host immune response. Existing therapies with nucleos(t)ide analogue or pegylated
      interferon are not sufficient to achieve a high rate of HBV surface antigen
      seroclearance, a more desirable treatment outcome. Novel therapeutic agents
      targeting alternative viral replication steps are being developed. In this
      review, we will discuss the hepatitis B core antigen (HBcAg) as a therapeutic
      target. Areas covered: The basic structure and fundamental functions of HBcAg
      including nucleocapsid assembly, pre-genomic RNA encapsidation, reverse
      transcription, virion formation, cccDNA amplification, immune response
      regulation, and HBx protein interaction will be reviewed. Most of these are
      identified as therapeutic targets and tested in in vitro and in vivo studies,
      although clinical trials are scanty. Among the different components, the core
      protein allosteric modulators (CpAM) have been most widely investigated and
      appear promising in clinical trials. Expert opinion: The multiple and essential
      functions of HBcAg for HBV life cycle are important and attractive targets for
      HBV therapeutic interventions. Controlled trials involving CpAM are awaited.
      Apart from CpAM, drugs directed against different functions of HBcAg may be
      further explored to maximize the chance of cure.

PMID- 29065734
TI  - Comparison of 22-gauge standard fine needle versus core biopsy needle for
      endoscopic ultrasound-guided sampling of suspected pancreatic cancer: a
      randomized crossover trial.
AB  - BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is
      effective for tissue diagnosis of pancreatic mass. To improve diagnostic yield
      and drawbacks, 22-gauge (G) core biopsy (FNB) needle has been developed. This
      study aims to compare 22G FNA and FNB needles for EUS-guided sampling of
      suspected pancreatic cancer. METHODS: This is a randomized controlled crossover
      trial. A total of 60 patients with suspected unresectable pancreatic cancer
      referred for EUS-guided sampling were randomly assigned to two groups. Both
      groups had 22G FNA and FNB needles performed in a randomized order. The primary
      endpoint was the cytological, histological and overall diagnostic accuracy of
      pancreatic cancer. RESULTS: FNA and FNB needles reported similar level of
      diagnostic accuracy (FNA needle 95% vs. FNB needle 93.3%; p = .564), and it was
      not statistically different. However, cytological cellularity was significantly
      higher in the FNB needles compared to FNA needles (odds ratio 2.75, 95%
      confidence interval (CI)). There were no procedure-related complications in both
      needles. CONCLUSIONS: The diagnostic accuracy of EUS-guided sampling for
      pancreatic cancer using 22G FNA is comparable to FNB needles. The cytological
      quality of specimen is better in the FNB needle.

PMID- 29065735
TI  - Phase I and II clinical trials for the mucopolysaccharidoses.
AB  - INTRODUCTION: The mucopolysaccharidoses are lysosomal diseases characterized by
      deficient activity of one of the enzymes that degrades glycosaminoglycans.
      Treatment options are limited; therefore, new treatments are under investigation.
      Areas covered: We review the medicinal products for the treatment of
      mucopolysaccharidoses that are currently being investigated in phase I and phase
      II clinical trials. Expert opinion: The number of alternatives to treat MPS
      diseases increased dramatically in an attempt to provide therapy options for
      orphan MPS diseases and to address the unmet needs of the MPS that already have a
      treatment available. Intravenous enzyme replacement therapy (ERT) with fusion
      proteins, intrathecal/intracerebroventricular (ICV) ERT and gene therapy are the
      most promising strategies addressing the CNS manifestations. Stop-codon read
      through, although proposed only for patients with nonsense mutations, might be
      useful in all MPS types. Substrate reduction therapy could also play a role in
      any MPS type, as anti-inflammatory drugs are also being tested. This new
      generation of therapies is now in clinical development and should bring new hope
      to MPS patients. As cost and logistics remain major challenges, especially for
      low- and middle-income countries, the possibility of having a one-time treatment
      such as gene therapy is anxiously awaited by affected families and healthcare
      systems.

PMID- 29065736
TI  - Investigation of possible maternal and fetal factors which affect umbilical
      coiling index.
AB  - AIM: The aim of this study was to investigate the possible maternal and fetal
      factors, which affect the Umbilical Coiling Index (UCI). METHODS: This
      prospective, observational, analytic study was conducted using the data of 380
      women with term pregnancy and newborns who presented at a University Hospital.
      Hemoglobin (Hb), ferritin, iron, and the total iron binding capacity (TIBC) of
      the maternal blood were measured, and transferrin saturation was estimated based
      on the ratio between serum iron and TIBC. Blood gases, ferritin, iron, and TIBC
      of the umbilical cord were also measured, and the transferrin saturation was
      calculated. The length and thickness of the umbilical cord, numbers of coilings,
      weight of placenta, neonatal weight were registered. The UCI was calculated
      dividing the total number of coils by the length of the umbilical cord (in cm).
      RESULTS: A positive, linear, and statistically significant relationship was found
      between the UCI scores and the umbilical cord blood transferrin saturation,
      umbilical cord thickness, and the first- and fifth-min APGAR scores (p = .044, p
      < .001, p = .008, p = .022, respectively). No statistically significant
      relationship was found between the maternal Hb values and the UCI scores (p =
      .472). In addition, there was no statistically significant relationship between
      the UCI scores and maternal ferritin, maternal transferrin saturation and
      umbilical cordon ferritin levels (p = .940, p = .681, and p = .975,
      respectively). CONCLUSIONS: A positive correlation was found between the UCI and
      umbilical cord transferrin saturation and between the newborn APGAR scores.
      However, this finding is not sufficient to explain the relationship of the
      umbilical cord dynamics with the newborn wellbeing and coiling.

PMID- 29065737
TI  - Comparison of complication and conversion rates between robotic-assisted and
      laparoscopic rectal resection for rectal cancer: which patients and providers
      could benefit most from robotic-assisted surgery?
AB  - AIMS: To compare (1) complication and (2) conversion rates to open surgery (OS)
      from laparoscopic surgery (LS) and robotic-assisted surgery (RA) for rectal
      cancer patients who underwent rectal resection. (3) To identify patient,
      physician, and hospital predictors of conversion. MATERIALS AND METHODS: A US
      based database study was conducted utilizing the 2012-2014 Premier Healthcare
      Data, including rectal cancer patients >=18 with rectal resection. ICD-9-CM
      diagnosis and procedural codes were utilized to identify surgical approaches,
      conversions to OS, and surgical complications. Propensity score matching on
      patient, surgeon, and hospital level characteristics was used to create
      comparable groups of RA?LS patients (n = 533 per group). Predictors of conversion
      from LS and RA to OS were identified with stepwise logistic regression in the
      unmatched sample. RESULTS: Post-match results suggested comparable perioperative
      complication rates (RA 29% vs LS 29%; p = .7784); whereas conversion rates to OS
      were 12% for RA vs 29% for LS (p < .0001). Colorectal surgeons (RA 9% vs LS 23%),
      general surgeons (RA 13% vs LS 35%), and smaller bed-size hospitals (RA 14% vs LS
      33%) have reduced conversion rates for RA vs LS (p < .0001). Statistically
      significant predictors of conversion included LS, non-colorectal surgeon, and
      smaller bed-size hospitals. LIMITATIONS: Retrospective observational study
      limitations apply. Analysis of the hospital administrative database was subject
      to the data captured in the database and the accuracy of coding. Propensity score
      matching limitations apply. RA and LS groups were balanced with respect to
      measured patient, surgeon, and hospital characteristics. CONCLUSIONS: Compared to
      LS, RA offers a higher probability of completing a successful minimally invasive
      surgery for rectal cancer patients undergoing rectal resection without
      exacerbating complications. Male, obese, or moderately-to-severely ill patients
      had higher conversion rates. While colorectal surgeons had lower conversion rates
      from RA than LS, the reduction was magnified for general surgeons and smaller bed
      size hospitals.

PMID- 29065738
TI  - Gestational diabetes mellitus and maternal breast cancer risk: a meta-analysis of
      the literature.
AB  - OBJECTIVE: The association between gestational diabetes mellitus (GDM) and
      maternal breast cancer risk was controversial and inclusive. In this study, we
      aimed to examine the association between GDM and maternal breast cancer using
      meta-analysis method. METHODS: Researchers searched and reviewed the topic
      related articles comprehensively. For each eligible article, we extracted the
      effect size (odds ratio/relative risk or OR/RR) and its 95% confidence interval
      (CI). We used random effect models to combine the effect sizes. Subgroups
      analysis were used to examine whether the effects of GDM on breast cancer risk
      differed across GDM ascertainment methods, breast cancer ascertainment method,
      risk of bias, and country of study origin. RESULTS: Five case-control studies and
      six cohort studies which met the eligible criteria were included into analysis.
      Overall, we didn't find significant associations between GDM and breast cancer
      among case-control studies (pooled OR = 0.85, 95%CI = 0.65, 1.10) and cohort
      studies pooled RR = 1.00, 95%CI = 0.80, 1.25). However, our subgroup analysis
      showed that GDM was a protective factor for breast cancer among the case-control
      studies in which breast cancer was ascertained via cancer registry system (OR =
      0.73, 95%CI = 0.54, 1.00). CONCLUSIONS: GDM during pregnancy is not associated
      with breast cancer in our study, suggesting that GDM mothers are not needed to be
      too anxious about their future breast cancer risk.

PMID- 29065740
TI  - Budget impact analysis on the introduction of a guideline based hepatitis B and C
      screening into a routine check-up in the German primary care setting.
AB  - OBJECTIVES: Systematic screening for chronic hepatitis B and C does not yet exist
      in Germany. Therefore, the implementation of a screening approach within a
      preventive medical examination performed by primary care physicians ('Check-Up
      35+') was evaluated in a recent prospective multicenter study. The present
      analysis estimates the financial consequences for the statutory health insurance
      by budget impact analysis. MATERIALS AND METHODS: A Markov cohort model was
      developed consisting of 21 health states. Four different screening scenarios
      derived from the previous multicenter study were compared to usual care, a
      strategy without screening for hepatitis. Actual cost data for Germany were
      calculated and systematic literature searches for all input parameters were
      performed. RESULTS: The base case results in incremental costs for the screening
      strategies compared to no hepatitis screening of 165-227 ? per patient in a 20
      year horizon. Two main parameters influence the financial consequences: (A)
      detection and treatment increase the costs in the beginning. (B) Screening avoids
      hepatitis induced end-stage liver disease. The initial higher costs exceed the
      later savings. Sensitivity analyses demonstrate a strong impact of medication
      costs for the treatment of additionally detected hepatitis infections on the
      outcome. This finding is robust to sensitivity analysis. CONCLUSIONS: The
      screening strategy proposed here implies additional costs for the statutory
      health insurance, however, a decision regarding its usefulness must consider
      criteria other than cost. For example, the high burden of disease due to liver
      cirrhosis and liver carcinoma should be considered. Therefore, an additional cost
      effectiveness-analysis should be conducted.

PMID- 29065739
TI  - Fecal calprotectin in management of Clostridium difficile infection: a
      longitudinal study.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is characterized by a relevant
      intestinal neutrophil infiltrate. So far, role of fecal calprotectin in CDI, has
      been investigated only in few studies, mainly focused on diagnosis of the
      disease. AIM: By a longitudinal design, we assess fecal calprotectin
      concentrations (FCCs) in subjects with CDI, evaluating the correlation between
      fecal marker and response to therapy. METHODS: Clinical (diarrhea scoring) and
      laboratory (FCCs and leucocytes count) evaluation was performed in 56 subjects
      with CDI at time of diagnosis (T0) and after a week from starting of therapy
      (T1). Clinical response to therapy at T1 was related with both T0 and T1 FCC
      values. FCCs were also related to all-cause 30-day mortality, recurrence and
      death, both of them within 90 days. RESULTS: FCCs at T1 were significantly
      increased in subjects with persistence of diarrhea in respect to the other ones
      (285.5 +/- 270 ug/g vs 150.7 +/- 147 ug/g, respectively; p < .05). Patients who
      did not respond to therapy showed higher, but not significative, FCCs at T0 than
      patients who responded. No correlation was found among FCCs, both at T0 and T1,
      and the other outcomes. CONCLUSIONS: Longitudinal evaluation of FCCs in patients
      with CDI could support physicians in clinical management of disease, for example
      in term of duration (10 vs 14 days) or type (first vs second line therapy).
      Further and larger studies could confirm the eventual role of this marker in
      prognostic algorithms, mainly in prediction of recurrence.

PMID- 29065741
TI  - Intra-incisional liposomal bupivacaine and its impact on postcesarean analgesia:
      a retrospective study.
AB  - PURPOSE: The efficacy of long-acting intraincisional bupivacaine in reducing
      postoperative opioid use among women who have undergone a cesarean is currently
      unknown. MATERIALS AND METHODS: This was a retrospective case-control study with
      a 1:1 allocation. We identified 40 patients in each group, for a total of 80. The
      treatment group was administered 266 mg of liposomal bupivacaine after completion
      of the cesarean and was compared to historical controls. Data regarding
      anesthesia administered, opioid consumption, nonsteroidal anti-inflammatory use,
      acetaminophen use, type of cesarean, reason for cesarean, and length of
      postoperative stay were recorded. RESULTS: The treatment group used 41.51 mg of
      morphine equivalents, while the control group consumed 69.90 mg (p < .001);
      multivariate analysis demonstrated a mean difference of 26.52 mg (95%CI 12.76
      40.28). Univariate analysis demonstrated mean difference in intravenous (IV)
      ketorolac (40.77 mg, p < .001) and IV acetaminophen (1333.33 mg, p < .001) was
      different and greater in the treatment group; this was controlled for in the
      multivariate model. There was no difference in oral and IV ibuprofen or oral
      acetaminophen use between groups. There were no differences between the type of
      anesthesia, length of stay, reason for cesarean, and classical sections between
      groups. CONCLUSIONS: Incisional administration of liposomal bupivacaine may be an
      effective adjunct in reducing opioid use postoperatively and may be a useful
      adjunct within an enhanced recovery program.

PMID- 29065742
TI  - Balloon sandwich technique for retrieval of fractured delivery wire of pipeline
      stent.
AB  - Delivery wire fracture of flow-diverter stents are rare but have been described.
      We describe a video case of a successful technique to retrieve such a fractured
      delivery wire by using a balloon microcatheter and the intermediate catheter when
      other proven methods may fail.

PMID- 29065743
TI  - A maternal death from self-induced medical abortion: a call for action.
AB  - OBJECTIVES: In Georgia, which has a longstanding, liberalised abortion law, the
      abortion procedure is generally safe if it is performed in a medical facility.
      However, when socioeconomic barriers prevent women from seeking safe abortion
      services, some risk their life by self-terminating an unintended pregnancy. We
      present a case of maternal mortality after a self-induced medical abortion, with
      the aim to investigate the underlying non-clinical causes of maternal death and
      the relevant policy implications. CASE: A 34-year-old socially vulnerable woman
      self-administered 10 tablets of oral misoprostol to terminate an 18-week
      pregnancy. She expelled the fetus the following day. A week later, she developed
      excessive vaginal bleeding, difficulty in breathing and tachycardia. She was
      hospitalised and diagnosed with sepsis due to a retained placenta. Uterine
      curettage and aggressive conservative management, followed by total abdominal
      hysterectomy, failed to stop the fulminant septic process. The patient's
      condition deteriorated rapidly and she died 15 h after admission to hospital.
      CONCLUSION: Socially disadvantaged women in Georgia have limited access to safe
      abortion services, and some are impelled to self-induce abortion in order to
      terminate an unintended pregnancy. Inclusion of family planning and abortion
      services in the Universal Health Care benefits package for socially vulnerable
      families may reduce the morbidity and mortality associated with unsafe abortion
      practices.

PMID- 29065745
TI  - Response to: Comment on: Essential competencies in global health research for
      medical trainees: A narrative review.

PMID- 29065746
TI  - Authors reply: statins and new onset of diabetes: which one outweighs risk or
      benefit?

PMID- 29065744
TI  - Exploring the potential cost-effectiveness of precision medicine treatment
      strategies for diffuse large B-cell lymphoma.
AB  - Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) is associated
      with worse survival after standard rituximab, cyclophosphamide, doxorubicin,
      vincristine, and prednisone (RCHOP) chemoimmunotherapy compared to germinal
      center B-cell-like (GCB) subtype. Preliminary evidence suggests that benefits
      from novel agents may vary by subtype. Hypothesizing that treatment stratified by
      DLBCL subtype could be potentially cost-effective, we developed micro-simulation
      models to compare three first-line treatment strategies: (1) standard RCHOP for
      all patients (2) subtype testing followed by RCHOP for GCB and novel treatment
      for ABC DLBCL, and (3) novel treatment for all patients. Based on phase 2
      evidence, we used lenalidomide + RCHOP as a surrogate novel treatment. The
      subtype-based approach showed a favorable incremental cost-effectiveness ratio of
      $15,015/quality-adjusted life year compared with RCHOP. Although our exploratory
      analyses demonstrated a wide range of conditions where subtype-based treatment
      remained cost-effective, data from phase 3 trials are needed to validate our
      models' findings and draw definitive conclusions.

PMID- 29065748
TI  - Twelve tips for teaching quality improvement in the clinical environment.
AB  - Medical educators are expected to teach quality improvement (QI) skills alongside
      traditional clinical skills such as physical examination and bedside manner.
      Educational resources for intensive training in QI have proliferated. However,
      many physicians lack the time or resources to undergo this training, and may
      struggle with teaching these skills to their learners. In response, we offer
      twelve tips to help physicians teach basic QI concepts in the clinical
      environment. By following these tips physicians will be able to engage their
      learners interest in QI and provide experiential learning that makes a lasting
      impact.

PMID- 29065747
TI  - A phase 1 trial of autologous stem cell transplantation conditioned with
      melphalan 200 mg/m2 and total marrow irradiation (TMI) in patients with
      relapsed/refractory multiple myeloma.
AB  - In this phase 1 study, we tested increasing doses of total marrow irradiation
      (TMI) in addition to standard intravenous melphalan at 200 mg/m2 (Mel200) in the
      conditioning regimen prior to autologous stem cell transplant (ASCT) for multiple
      myeloma (NCT02043847). Twelve patients aged 18-75 with relapsed myeloma were
      enrolled in the study and received Mel200 and TMI 3 Gy (n = 3), 6 Gy (n = 3), or
      9 Gy (n = 6) prior to transplant. There were no grade 4 extra-hematologic
      toxicities and a maximum tolerated dose was not reached. Median time to
      neutrophil and platelet engraftment was 11 and 13 d, respectively. At day 90, 73%
      of patients were in CR or VGPR. Median progression free survival (PFS) was 449 d
      and median overall survival (OS) was 966 d. We conclude that TMI at a dose of 9
      Gy can be safely combined with Mel200 in therapeutic regimens for autologous
      transplant. Initial clinical results will prompt a phase 2 study.

PMID- 29065750
TI  - Twelve tips for efficient procedural simulation.
AB  - Procedural simulation (PS) is increasingly being used worldwide in healthcare for
      training caregivers in psychomotor competencies. It has been demonstrated to
      improve learners' confidence and competence in technical procedures, with
      consequent positive impacts on patient outcomes and safety. Several frameworks
      can guide healthcare educators in using PS as an educational tool. However, no
      theory-informed practical framework exists to guide them in including PS in their
      training programs. We present 12 practical tips for efficient PS training that
      translates educational concepts from theory to practice, based on the existing
      literature. In doing this, we aim to help healthcare educators to adequately
      incorporate and use PS both for optimal learning and for transfer into
      professional practice.

PMID- 29065749
TI  - Chronic periodontitis, inflammatory cytokines, and interrelationship with other
      chronic diseases.
AB  - Periodontal diseases, such as chronic periodontitis, share common inflammatory
      risk factors with other systemic and chronic inflammatory disorders. Mucosal
      tissues, such as oral epithelia, are exposed to environmental stressors, such as
      tobacco and oral bacteria, that might be involved in promoting a systemic
      inflammatory state. Conversely, chronic disorders can also affect oral health.
      This review will summarize recent evidence for the interrelationship between
      chronic periodontitis and other prevalent chronic diseases such as cardiovascular
      diseases, diabetes, cancer and chronic respiratory diseases. The association with
      pregnancy is also included due to possible obstetric complications. We will focus
      on inflammatory cytokines such as TNF-alpha, IL-1, and IL-6, because they have
      been shown to be increased in patients with chronic periodontitis, in patients
      with chronic systemic diseases, and in patients with both chronic periodontitis
      and other chronic diseases. Therefore, an imbalance towards a proinflammatory
      immune response could underline a bidirectional link between chronic
      periodontitis and other chronic diseases. Finally, we highlight that a close
      coordination between dental and other health professionals could promote oral
      health and prevent or ameliorate other chronic diseases.

PMID- 29065751
TI  - Assessing staff-oriented care with developmental support approach in Iranian
      NICUs.
AB  - BACKGROUND: Regarding improvements in preterm infants' survival rates, it is
      necessary the improvement of Neonatal Intensive Care Unit (NICUs) status in order
      to provide comprehensive care. The aim of this study was to assess the aspects of
      staffing-oriented neonatal care in NICUs affiliated to Universities of Medical
      Sciences in Iran. METHODS: This survey is a cross-sectional study which was
      conducted in 23 NICUs of nine type-1 Universities of Medical Sciences across
      country. The study checklist contained 39 items in four domains, including
      "Composition, Philosophy, Training, and Support", "Management", "Resources", and
      "Transition Systems". Data were gathered through observation and analyzed using
      Stata software, version 13. RESULTS: In this study, the mean score of staffing
      oriented care was 43.5 of 100. In none of the studied domains, the mean score
      obtained was not above 50. Among the four domains studied, the highest score was
      related to "Management", (the mean score of 50 of 100) and the lowest score
      related to "Resources" (the mean score of 35 of 100). CONCLUSIONS: Considering
      the importance of the role of health professionals in the neonatal comprehensive
      care, and also the low mean score of staffing-oriented care (43.51 out of 100)
      and also its items in NICUs in this study, it is concluded that more attention is
      needed for staff-oriented care as well as the strengthening of this dimension of
      developmental care along with other dimensions, through designing of appropriate
      interventions to improve the health outcomes of preterm infants.

PMID- 29065752
TI  - Is blood transfusion necessary in all patients with disseminated intravascular
      coagulation associated postpartum hemorrhage?
AB  - OBJECTIVE: The diagnosis of disseminated intravascular coagulation (DIC) in
      obstetrics is complicated owing to physiological changes, particularly during
      late pregnancy and the postpartum period. Therefore, a pregnancy-modified DIC
      score that includes only three components of the International Society on
      Thrombosis and Hemostasis (ISTH) DIC score has been constructed. Our aim was to
      determine how many blood-transfused postpartum women actually had the diagnosis
      of overt DIC according to the modified ISTH score and had the correct indications
      for blood transfusion. METHODS: We retrospectively analyzed 279 women who had
      received transfusion of at least two units of blood for postpartum hemorrhage. We
      used the modified ISTH score for DIC, which is based on platelet count,
      fibrinogen concentration, and prothrombin time (PT) differences. A total score of
      26 points or higher indicated overt DIC, whereas a score lower than 26 points
      represented nonovert DIC. RESULTS: According to the modified ISTH score, 100 of
      the 279 patients (35.8%) had overt DIC, with a median DIC score of 37.0. Thirty
      five percent of patients in the overt DIC group and 25.7% in the nonovert DIC
      group had received more than four units of blood. The levels of PT and activated
      partial thromboplastin time were higher, and the fibrinogen level was lower in
      patients with overt DIC. CONCLUSIONS: According to the modified ISTH score, we
      found that blood transfusion was unnecessary in 179 of the 279 postpartum women
      (64.1%). If this scoring system is used to determine which patients should be
      transfused, unnecessary transfusions and their related risks and complications
      will be prevented.

PMID- 29065754
TI  - Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a
      prospective study.
AB  - OBJECTIVE: To explore the gestational age of early-onset intrahepatic cholestasis
      (ICP) of pregnancy, and to analyze the relationship between the clinical
      biochemical indices and pregnancy outcomes in order to arrive at a reasonable
      diagnosis and administer appropriate treatment. DESIGN: This is a retrospective
      clinical study. POPULATION OR SAMPLE: We selected 47,260 pregnant women who
      received prenatal care and underwent childbirth at the International Peace
      Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University
      from January 2014 to December 2016 for participating in this study. Of these
      47,260 women, 407 developed ICP. METHODS: To calculate the gestational week
      cutoff between early- and late-onset ICP by the receiver-operating characteristic
      (ROC) curve and Youden's index. Two independent samples t tests and chi square
      test were used to compare the differences in biochemical indices and pregnancy
      outcomes between the two groups. RESULTS: We found that 34 weeks is the most
      appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early
      onset ICP is characterized by early onset, long disease duration and a higher
      incidence of preterm labor, fetal distress, and fetal low birth weight compared
      to late-onset ICP. CONCLUSIONS: Thirty-four weeks is the most appropriate cutoff
      gestational age for the diagnosis of early-onset ICP. And to reduce the adverse
      pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation
      up to 37 weeks as far as possible before selecting iatrogenic birth.

PMID- 29065753
TI  - Perioperative adjuvant corticosteroids for postoperative analgesia in knee
      arthroplasty.
AB  - Background and purpose - Immediate postoperative pain management offered in knee
      arthroplasty is suboptimal in up to one-third of patients resulting in high
      opiate consumption and delayed discharge. In this meta-analysis we investigate
      the analgesic effect and safety of perioperative adjuvant corticosteroids in knee
      arthroplasty. Methods - Databases Medline, Embase, and Central were searched for
      randomized studies comparing the analgesic effect of adjuvant perioperative
      corticosteroids in knee arthroplasty. Our primary outcome was pain score at 24
      hours postoperatively. Secondary outcomes included pain at 12, 48, and 72 hours,
      opiate consumption, postoperative nausea and vomiting, infection, and discharge
      time. Systemic (intravenous) and local (intra-articular) corticosteroids were
      analyzed separately. Results - 14 randomized controlled trials (1,396 knees) were
      included. Mean corticosteroid dosages were predominantly 50-75mg oral
      prednisolone equivalents for both systemic and local routes. Systemic
      corticosteroids demonstrated statistically significant and clinically modest
      reductions in pain at 12 hours by -1.1 points (95%CI -2.2 to 0.02), 24 hours by 
      1.3 points (CI -2.3 to -0.26) and 48 hours by -0.4 points (CI -0.67 to -0.04).
      Local corticosteroids did not reduce pain. Opiate consumption, postoperative
      nausea and vomiting, infection, or time till discharge were similar between
      groups. Interpretation - Corticosteroids modestly reduce pain postoperatively at
      12 and 24 hours when used systemically without any increase in associated risks
      for dosages between 50 and 75 mg oral prednisolone equivalents.

PMID- 29065755
TI  - Improving empathy in medical students: The role of patient tutors.

PMID- 29065758
TI  - Poster Session 1.

PMID- 29065757
TI  - MSParis2017 Committees.

PMID- 29065759
TI  - Late Breaking News Abstracts.

PMID- 29065761
TI  - Poster Session 2.

PMID- 29065763
TI  - ePosters.

PMID- 29065764
TI  - Recognition and stabilization of geranylgeranylated human Rab5 by the GDP
      Dissociation Inhibitor (GDI).
AB  - The small GTPase Rab5 is the key regulator of early endosomal fusion. It is post
      translationally modified by covalent attachment of two geranylgeranyl (GG) chains
      to adjacent cysteine residues of the C-terminal hypervariable region (HVR). The
      GDP dissociation inhibitor (GDI) recognizes membrane-associated Rab5(GDP) and
      serves to release it into the cytoplasm where it is kept in a soluble state. A
      detailed new structural and dynamic model for human Rab5(GDP) recognition and
      binding with human GDI at the early endosome membrane and in its dissociated
      state is presented. In the cytoplasm, the GDI protein accommodates the GG chains
      in a transient hydrophobic binding pocket. In solution, two different binding
      modes of the isoprenoid chains inserted into the hydrophobic pocket of the
      Rab5(GDP):GDI complex can be identified. This equilibrium between the two states
      helps to stabilize the protein-protein complex in solution. Interprotein contacts
      between the Rab5 switch regions and characteristic patches of GDI residues from
      the Rab binding platform (RBP) and the C-terminus coordinating region (CCR)
      reveal insight on the formation of such a stable complex. GDI binding to membrane
      anchored Rab5(GDP) is initially mediated by the solvent accessible switch regions
      of the Rab-specific RBP. Formation of the membrane-associated Rab5(GDP):GDI
      complex induces a GDI reorientation to establish additional interactions with the
      Rab5 HVR. These results allow to devise a detailed structural model for the
      process of extraction of GG-Rab5(GDP) by GDI from the membrane and the
      dissociation from targeting factors and effector proteins prior to GDI binding.

PMID- 29065766
TI  - Short report letter: Three-dimensional printed anatomical models in scaphoid
      surgery.

PMID- 29065767
TI  - Results of heterodigital flexor digitorum profundus hemi-tendon transfer for 23
      flexor tendon injuries in zones 1 or 2.
AB  - : We report outcomes of reconstruction of zone 1 or 2 flexor tendon injuries
      using a heterodigital hemi-tendon transfer of the flexor digitorum profundus in
      23 fingers of 23 patients. At mean follow-up of 57 months, the mean total active
      motion of the three finger joints including the metacarpophalangeal joint was 128
      degrees preoperatively and 229 degrees at final follow up. According to
      Strickland criteria, the function was excellent for 14 fingers, good for seven
      fingers and poor for two fingers. The subgroup analysis showed that the results
      were better in cases of primary surgery, children, and for the index and little
      fingers. Complications included stiffness of three fingers, and rupture in one
      finger that was converted to a two-stage tendon reconstruction. We conclude that
      this technique restores good function in most patients with zone 1 and 2 flexor
      tendon injuries, in which primary tendon repair has not been performed or was
      unsuccessful, and where pulley reconstruction is not required. LEVEL OF EVIDENCE:
      IV.

PMID- 29065765
TI  - Rolipram-Loaded Polymeric Micelle Nanoparticle Reduces Secondary Injury after Rat
      Compression Spinal Cord Injury.
AB  - Among the complex pathophysiological events following spinal cord injury (SCI),
      one of the most important molecular level consequences is a dramatic reduction in
      neuronal cyclic adenosine monophosphate (cAMP) levels. Many studies shown that
      rolipram (Rm), a phosphodiesterase IV inhibitor, can protect against secondary
      cell death, reduce inflammatory cytokine levels and immune cell infiltration, and
      increase white matter sparing and functional improvement. Previously, we
      developed a polymeric micelle nanoparticle, poly(lactide-co-glycolide)-graft
      polyethylenimine (PgP), for combinatorial delivery of therapeutic nucleic acids
      and drugs for SCI repair. In this study, we evaluated PgP as an Rm delivery
      carrier for SCI repair. Rolipram's water solubility was increased ~6.8 times in
      the presence of PgP, indicating drug solubilization in the micelle hydrophobic
      core. Using hypoxia as an in vitro SCI model, Rm-loaded PgP (Rm-PgP) restored
      cAMP levels and increased neuronal cell survival of cerebellar granular neurons.
      The potential efficacy of Rm-PgP was evaluated in a rat compression SCI model.
      After intraspinal injection, 1,1'-dioctadecyl-3,3,3',3'-tetramethyl
      indotricarbocyanine Iodide-loaded PgP micelles were retained at the injection
      site for up to 5 days. Finally, we show that a single injection of Rm-PgP
      nanoparticles restored cAMP in the SCI lesion site and reduced apoptosis and the
      inflammatory response. These results suggest that PgP may offer an efficient and
      translational approach to delivering Rm as a neuroprotectant following SCI.

PMID- 29065768
TI  - Clinical characteristics of generalized anxiety disorder: older vs. young adults.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common anxiety
      disorders in older people. Although GAD in older adults seems to differ in many
      aspects like clinical presentation, severity and treatment response, there is a
      paucity of comparative research. AIMS: The aim of the study is to compare the
      clinical presentation of GAD between older and young adults. METHODS: One hundred
      and two non-demented older patients (age >=65) and 64 young patients (age <45)
      who were diagnosed with GAD according to the DSM-IV-TR criteria were included to
      the study. Socio-demographic Data Form, the Structured Clinical Interview for DSM
      Disorders-1 (SCID-1), the Questionnaire for the Suggested Behavioral Criteria of
      GAD for DSM-5, the Hamilton Depression Scale (HAM-D), the Generalized Anxiety
      Disorder Severity Scale (GADSS) and the Sheehan Disability Scale (SDS) were
      applied to both groups. RESULTS AND CONCLUSIONS: Older GAD patients had more
      disturbances of sleep, less reassurance seeking behaviors, higher rates of
      depression and higher depression severity when compared to the young patients.
      Although older people seemed to have a lower severity of GAD, they had higher
      disability due to worries. Older patients worried more about their own health and
      family well-being, whereas young patients worried more about future and other's
      health.

PMID- 29065770
TI  - Salivary cortisol reactivity in preschoolers is associated with hair cortisol and
      behavioral problems.
AB  - The interplay between children's cortisol reactivity to challenge and cumulative
      cortisol exposure is not well understood. Examining the role of cortisol
      reactivity in early childhood may elucidate biological mechanisms that contribute
      to children's chronic physiological stress and behavioral dysregulation. In a
      sample of 65 preschool-aged children, we examined the relation between children's
      salivary cortisol reactivity to challenging tasks and their hair cortisol
      concentration (HCC). While both are biomarkers of the hypothalamic-pituitary
      adrenal (HPA) axis, salivary cortisol reactivity reflects an acute cortisol
      response to a stressor and HCC reflects cumulative cortisol exposure. In
      addition, we examined the relations of these stress biomarkers with internalizing
      and externalizing problems. Salivary cortisol reactivity was associated with
      higher HCC and with increased externalizing behaviors. Child HCC also was
      positively correlated with parent HCC. Results highlight the contributions of
      salivary cortisol reactivity to children's cumulative cortisol exposure, which
      may add to their biological risk for health problems later. The observed
      association between externalizing problems and salivary cortisol reactivity
      indicates concordances between dysregulated behavioral reactions and dysregulated
      cortisol responses to challenges. The finding that salivary cortisol reactivity
      to challenge in early childhood plays a role in children's cumulative cortisol
      exposure and behavioral development suggests pathways through which cortisol
      reactivity may influence long-term physical and mental health.

PMID- 29065771
TI  - On the periphery of HIV and AIDS: Reflections on stress as experienced by
      caregivers in a child residential care facility in South Africa.
AB  - Few researchers have investigated how female caregivers of institutionalised
      children, especially those affected by HIV and AIDS, experience stress. The role
      played by caregivers cannot be overemphasised; yet caregivers who work in
      institutions caring for orphaned and/or abandoned children affected by HIV and
      AIDS, are often marginalised and on the periphery of the HIV and AIDS pandemic.
      The implication is that insufficient attention or consideration is given to the
      importance of the role they play in these children's lives. The objective of the
      study was to explore how female caregivers of institutionalised children affected
      by HIV and AIDS experience stress. A qualitative research project with a case
      study design was conducted. The purposively selected participants from a
      previously identified care facility were seven females in the age ranges of 35
      59. Data was gathered during individual interviews and focus group discussions.
      Thematic content analysis of the data yielded the following themes: (1)
      contextualising caregiving as 'work'; (2) stresses linked to caregiving; and (3)
      coping with stress. Findings from this study indicated that participants
      experienced caregiving in an institution as stressful, demotivating, and
      emotionally burdensome. Moreover, caregivers working in an environment of HIV and
      AIDS experienced additional stress related to organisational and management
      impediments, lack of emotional and practical support, inadequate training,
      discipline difficulties, and lack of respect and appreciation from the children
      in their care. It is recommended that training and management support as well as
      personal support and counselling for caregivers in the institutional context
      could help them to cope better, feel empowered and to potentially elevate their
      status as valued members of society.

PMID- 29065772
TI  - The impact of Chlamydia trachomatis infection on sperm parameters and male
      fertility: A comprehensive study.
AB  - Chlamydia trachomatis (CT), an obligate intracellular bacterium, requires living
      cells to replicate. Half of men infected with CT are asymptomatic. CT infection
      can persist for up to four years within couples and affect their fertility.
      Chlamydia infection in men acts as a reservoir for transmission to women and can
      cause urinary tract inflammation, sperm DNA damage, and acute epididymitis. Semen
      samples from 1080 subfertile patients with normal and abnormal spermograms were
      examined to detect the presence of CT. An ELISA test was used to detect the
      presence of anti-CT IgA in these patients' seminal plasma. CT infection was also
      confirmed by molecular investigation using specific primers. In order to evaluate
      the effect of CT infections on the DNA Fragmentation Index (DFI), 40 CT-infected
      cases and 20 CT-negative controls were analyzed by a Sperm Chromatin Structure
      Assay using flow cytometry. Among 1080 patients with poor sperm parameters, 155
      (14.3%) patients were diagnosed with CT, 11% among those with semen abnormalities
      and 26% among those without semen abnormalities patients. The DFI was
      statistically higher in cases than in controls (p < 0.05). Given the prevalence
      of infection and also the high frequency of asymptomatic CT infection among
      infertile individuals with poor sperm parameters, screening for infection in
      these patients is essential in order to avoid adverse sequelae. We propose that
      the higher rate of DFI in CT-infected infertile men might be an underlying cause
      of their infertility and this warrants greater attention.

PMID- 29065769
TI  - Imaging of Cerebrovascular Function in Chronic Traumatic Brain Injury.
AB  - Traumatic cerebrovascular injury (TCVI) is a common pathologic mechanism of
      traumatic brain injury (TBI) and presents an attractive target for intervention.
      The aims of this study were to assess cerebral blood flow (CBF) and
      cerebrovascular reactivity (CVR) using magnetic resonance imaging (MRI) to assess
      their value as biomarkers of TCVI in chronic TBI, characterize the spatial
      distribution of TCVI, and assess the relationships between each biomarker and
      neuropsychological and clinical assessments. Forty-two subjects (27 chronic TBI,
      15 age- and gender-matched healthy volunteers) were studied cross-sectionally.
      CBF was measured by arterial spin labeling and CVR by assessing the MRI-blood
      oxygen level-dependent signal with hypercapnia challenge. A focused
      neuropsychological battery adapted from the TBI Common Data Elements and
      neurobehavioral symptom questionnaires were administered at the time of the
      imaging session. Chronic TBI subjects showed a significant reduction in mean
      global, gray matter (GM), and white matter (WM) CVR, compared with healthy
      volunteers (p < 0.001). Mean GM CVR had the greatest effect size (Cohen's d =
      0.9). CVR maps in chronic TBI subjects showed patchy, multifocal CVR deficits.
      CBF discriminated poorly between TBI subjects and healthy volunteers and did not
      correlate with CVR. Mean global CVR correlated best with chronic neurobehavioral
      symptoms among TBI subjects. Global, GM, and WM CVR are reliable and potentially
      useful biomarkers of TCVI in the chronic stage after moderate-to-severe TBI. CBF
      is less useful as biomarker of TCVI. CVR correlates best with chronic TBI
      symptoms. CVR has potential as a predictive and pharmacodynamic biomarker for
      interventions targeting TCVI.

PMID- 29065773
TI  - Describing and expanding the clinical phenotype of anti-MDA5-associated rapidly
      progressive interstitial lung disease: case series of nine Canadian patients and
      literature review.
AB  - OBJECTIVE: To describe and expand the phenotype of anti-MDA5-associated rapidly
      progressive interstitial lung disease (MDA5-RPILD) in Canadian patients. METHOD:
      All proven cases of MDA5-RPILD hospitalized in the University of Montreal's
      affiliated centres from 2004 to 2015 were selected for inclusion. RESULTS: Of
      nine consecutive patients, RPILD was the presenting manifestation in seven,
      whereas two patients developed RPILD 2 years after the onset of arthritis and of
      chronic interstitial lung disease. In the case with arthritis, RPILD was probably
      triggered by initiation of tumour necrosis factor-alpha-inhibitor therapy. In
      most patients (89%), RPILD was accompanied by concomitant onset of palmar/lateral
      finger papules, skin ulcerations, and/or mechanic's hands. All patients
      experienced profound weight loss over 1-2 months (mean +/- SD 10.2 +/- 4.8 kg).
      All had arthralgias and/or arthritis. Six patients were clinically amyopathic;
      only one patient had creatine kinase (CK) levels > 500 U/L. Initial ferritin and
      transaminase levels were elevated in 86% and 67% of patients, respectively. The
      antinuclear antibody (ANA) test was negative for nuclear and cytoplasmic
      staining; antisynthetase autoantibodies were negative. Three patients died; time
      from initial symptoms to death ranged from 7 to 15 weeks. All six survivors
      received mycophenolate mofetil and/or tacrolimus as part of induction and/or
      maintenance therapy. CONCLUSION: In an inpatient setting, RPILD associated with
      characteristic skin rashes, profound weight loss, articular symptoms, normal or
      low CK with elevated ferritin, and absent fluorescence on ANA testing should
      alert the clinician to the possibility of MDA5-RPILD. T-cell-mediated therapies
      may play a role in this highly lethal condition.

PMID- 29065774
TI  - State-of-the-art robotic devices for ankle rehabilitation: Mechanism and control
      review.
AB  - There is an increasing research interest in exploring use of robotic devices for
      the physical therapy of patients suffering from stroke and spinal cord injuries.
      Rehabilitation of patients suffering from ankle joint dysfunctions such as drop
      foot is vital and therefore has called for the development of newer robotic
      devices. Several robotic orthoses and parallel ankle robots have been developed
      during the last two decades to augment the conventional ankle physical therapy of
      patients. A comprehensive review of these robotic ankle rehabilitation devices is
      presented in this article. Recent developments in the mechanism design, actuation
      and control are discussed. The study encompasses robotic devices for treadmill
      and over-ground training as well as platform-based parallel ankle robots. Control
      strategies for these robotic devices are deliberated in detail with an emphasis
      on the assist-as-needed training strategies. Experimental evaluations of the
      mechanism designs and various control strategies of these robotic ankle
      rehabilitation devices are also presented.

PMID- 29065775
TI  - A risk-factor analysis of medical litigation judgments related to fall injuries
      in Korea.
AB  - The aim of this study was to find out the risk factors through analysis of seven
      medical malpractice judgments related to fall injuries. The risk factors were
      analysed by using the framework that approaches falls from a systems perspective
      and comprised people, organisational or environmental factors, with each factor
      being comprised of subfactors. The risk factors found in each of the seven
      judgments were aggregated into one framework. The risk factors related to
      patients (i.e. the people factor) were age, pain, related disease, activities and
      functional status, urination state, cognitive function impairment, past history
      of fall, blood transfusion, sleep endoscopy state and uncooperative attitude. The
      risk factors related to the medical staff and caregivers (i.e. people factor)
      were observation negligence, no fall prevention activities and negligence in
      managing high-risk group for fall. Organisational risk factors were a lack of
      workforce, a lack of training, neglecting the management of the high-risk group,
      neglecting the management of caregivers and the absence of a fall prevention
      procedure. Regarding the environment, the risk factors were found to be the
      emergency room, chairs without a backrest and the examination table. Identifying
      risk factors is essential for preventing fall accidents, since falls are
      preventable patient-safety incidents. Falls do not happen as a result of a single
      risk factor. Therefore, a systems approach is effective to identify risk factors,
      especially organisational and environmental factors.

PMID- 29065777
TI  - How do associative and phonemic overlap interact to boost illusory recollection?
AB  - This project investigated the underlying mechanisms that boost false remember
      responses when participants receive study words that are both semantically and
      phonologically similar to a critical lure. Participants completed a memory task
      in which they were presented with a list of words all associated with a critical
      lure. Included within the list of semantic associates was a target that was
      either semantically associated (e.g., yawn) to the critical lure (e.g., sleep) or
      shared the initial (e.g., slam) or final (e.g., beep) phoneme(s) with the
      critical lure. After hearing the list, participants recalled each list item and
      indicated whether they just knew it was on the list or if they instead
      recollected specific contextual details of that item's presentation. We found
      that inserting an initial phonemic overlap target boosted experiences of
      recollection, but only when semantically related associates were presented
      beforehand. The results are consistent with models of spoken word recognition and
      show that established semantic context plus initial phonemic overlap play
      important roles in boosting false recollection.

PMID- 29065778
TI  - Upregulation of VEGFR1 in a rat model of esophagogastric anastomotic healing.
AB  - INTRODUCTION: Anastomotic leakage after gastrointestinal surgery is a significant
      cause of morbidity and mortality. Esophagogastric and colorectal anastomoses are
      vulnerable to leakage. Extended knowledge of growth factors and their receptors
      is needed to understand anatomic healing. METHODS: The expression pattern of
      vascular growth factor receptor (VEGFR1-3), epidermal growth factor receptor
      (EGFR), platelet-derived growth factor receptor (PDGFRalpha/beta) and
      keratinocyte growth factor receptor (KGFR) were analyzed by semiquantitative-PCR
      in the rat intestinal tract and in esophagogastric anastomosis 5d after surgery.
      RESULTS: VEGFR1, VEGFR2, EGFR, KGFR and PDGFRalpha expression was observed
      throughout the intestinal tract including esophagus, stomach, small bowl and
      colon. VEGFR3 was not found in gastric samples and PDGFRbeta expression was not
      detected in the small bowl. Semiquantitative analyses of the VEGFR1, PDGFRalpha
      and EGFR expression in esophagogastric anastomotic tissues revealed a 2-fold
      upregulation of the VEGFR1 in gastric samples, while no change was observed in
      the esophageal anastomotic side. CONCLUSION: Our results revealed a distinct
      expression pattern of the investigated growth factor receptors in rat intestinal
      tract. Showing higher expression levels of growth factor receptors at the gastric
      anastomotic tissue at the fifth postoperative day suggests a different
      contribution of the gastric and the esophageal side to the anastomotic healing.

PMID- 29065776
TI  - Phosphate Functional Groups Improve Oligo[(Polyethylene Glycol) Fumarate]
      Osteoconduction and BMP-2 Osteoinductive Efficacy.
AB  - Off-the-shelf availability in large quantities, drug delivery functionality, and
      modifiable chemistry and mechanical properties make synthetic polymers highly
      suitable candidates for bone grafting. However, most synthetic polymers lack the
      ability to support cell attachment, proliferation, migration, and
      differentiation, and ultimately tissue formation. Incorporating anionic peptides
      into the polymer that mimics acidic proteins, which contribute to
      biomineralization and cellular attachment, could enhance bone formation.
      Therefore, this study investigates the effect of a phosphate functional group on
      osteoconductivity and BMP-2-induced bone formation in an injectable and
      biodegradable oligo[(polyethylene glycol) fumarate] (OPF) hydrogel. Three types
      of OPF hydrogels were fabricated using 0%, 20%, or 40% Bis(2
      (methacryloyloxy)ethyl) phosphate creating unmodified OPF-noBP and phosphate
      modified OPF-BP20 and OPF-BP40, respectively. To account for the osteoinductive
      effect of various BMP-2 release profiles, two different release profiles (i.e.,
      different ratios of burst and sustained release) were obtained by varying the BMP
      2 loading method. To investigate the osteoconductive effect of phosphate
      modification, unloaded OPF composites were assessed for bone formation in a bone
      defect model after 3, 6, and 9 weeks. To determine the effect of the hydrogel
      phosphate modification on BMP-2-induced bone formation, BMP-2 loaded OPF
      composites with differential BMP-2 release were analyzed after 9 weeks of
      subcutaneous implantation in rats. The phosphate-modified OPF hydrogels (OPF-BP20
      and OPF-BP40) generated significantly more bone in an orthotopic defect compared
      to the unmodified hydrogel (OPF-noBP). Furthermore, the phosphate functionalized
      surface-enhanced BMP-2-induced ectopic bone formation regardless of the BMP-2
      release profile. In conclusion, this study clearly shows that phosphate
      functional groups improve the osteoconductive properties of OPF and enhanced BMP
      2-induced bone formation. Therefore, functionalizing hydrogels with phosphate
      groups by crosslinking monomers into the hydrogel matrix could provide a valuable
      method for improving polymer characteristics and holds great promise for bone
      tissue engineering.

PMID- 29065779
TI  - Open surgery for iliofemoral deep vein thrombosis with temporary arteriovenous
      fistula remains valuable.
AB  - Objective We assessed outcomes of open surgical venous thrombectomy with
      temporary arteriovenous fistula, and the procedure's effect on health-related
      quality of life. Method We retrospectively analyzed 48 (26 at long-term) patient
      medical records. Mortality rates, patency, and risk of post-thrombotic syndrome
      were analyzed using Kaplan-Meier estimation. The association between risk
      factors/coagulation disorders and patency/post-thrombotic syndrome along with
      patient health-related quality of life at long-term was analyzed employing
      various statistical methods. Results Patient one-year survival rate was 93 +/- 4%
      and primary one-year patency rate was 89 +/- 5% (secondary one-year patency rate
      97 +/- 3%). Freedom from post-thrombotic syndrome after eight years was 80 +/-
      12% (post-thrombotic syndrome rate 20 +/- 12%). Health-related quality of life
      was impaired vs. normative data in the physical and social subscales, and in the
      mental component score ( p < .05). Conclusions Open surgical venous thrombectomy
      appears safe compared with literature-reported outcomes in similar patients using
      alternative approaches. Iliofemoral deep vein thrombosis impairs physical,
      social, and mental health-related quality of life.

PMID- 29065781
TI  - Several studies with significant C1 attention effects survive critical analysis.
AB  - In a discussion paper (Slotnick, this issue), I conducted a selective review of
      spatial attention studies to compare experimental parameters and determine
      whether particular stimulus, task, or analysis conditions were more likely to
      produce significant attentional modulation of the event-related potential (ERP)
      C1 component. It was concluded that to maximize C1 attention effects, stimuli
      should be in the upper visual field, there should be distractors, conditions
      should be high perceptual or attentional load, there should be exogenous cuing,
      and effects should be measured at midline parietal-occipital electrodes POz, Pz,
      and CPz. Commentaries were received by Fu (this issue), Qu and Ding (this issue),
      Zani and Proverbio (this issue), Pitts and Hillyard (this issue), Di Russo (this
      issue), and Mohr and Kelly (this issue). Comments included additional ideas to
      amplify C1 attention effects, support for some conclusions, and challenges to
      some conclusions. The challenges led to a more in depth analysis of many issues
      pertaining to C1 attention effects including optimal electrode and stimulus
      locations, null V1 source localization attention effects, whether all significant
      C1 attention effects can be discounted, and the number of studies with null
      versus significant C1 attention effects. Analysis of the studies that survived
      critical analysis, which included several that observed significant C1 attention
      effects, led to the same conclusions as Slotnick (this issue). Lines of future
      research include replicating studies that have observed C1 attention effects
      using identical experimental parameters and systematically manipulating
      parameters to determine the impact of each parameter on C1 spatial attention
      effects.

PMID- 29065780
TI  - Health literacy and current CD4 cell count in a multiethnic U.S. sample of adults
      living with HIV infection.
AB  - Hispanic and Black adults are disproportionately affected by HIV and experience
      poorer HIV-related health outcomes relative to non-Hispanic White adults. The
      current study adopted Sorensen's integrated model to test the hypothesis that
      lower functional and critical health literacy competencies contribute to poorer
      HIV-related health and CD4 cell count for Hispanic and Black individuals. Eighty
      one non-Hispanic White, Hispanic, and Black HIV seropositive individuals from a
      large, Southwestern metropolitan area were administered measures of health
      literacy, including the Expanded Numeracy Scale, Newest Vital Sign, Rapid
      Estimate of Adult Literacy in Medicine, Test of Functional Health Literacy
      (TOHFLA)-numeracy, and TOHFLA-reading. Hispanic and Black individuals
      demonstrated less HIV knowledge than non-Hispanic White individuals. Black
      participants demonstrated fewer health literacy appraisal skills. Importantly,
      lower levels of health literacy were linked to poorer CD4 cell count (an index of
      immune functioning) for Hispanic and Black individuals and not for non-Hispanic
      White individuals. These findings suggest race group differences for health
      literacy on current CD4 cell count such as very specific dimensions of low health
      literacy (e.g. poorer judgment of health-related information), but not other
      presumed deficits (e.g. motivation, access), play an important role in clinical
      health outcomes in HIV.

PMID- 29065782
TI  - The use of regression tree analysis for predicting the functional outcome
      following traumatic spinal cord injury.
AB  - Predicting the long-term functional outcome following traumatic spinal cord
      injury is needed to adapt medical strategies and to plan an optimized
      rehabilitation. This study investigates the use of regression tree for the
      development of predictive models based on acute clinical and demographic
      predictors. This prospective study was performed on 172 patients hospitalized
      following traumatic spinal cord injury. Functional outcome was quantified using
      the Spinal Cord Independence Measure collected within the first-year post injury.
      Age, delay prior to surgery and Injury Severity Score were considered as
      continuous predictors while energy of injury, trauma mechanisms, neurological
      level of injury, injury severity, occurrence of early spasticity, urinary tract
      infection, pressure ulcer and pneumonia were coded as categorical inputs. A
      simplified model was built using only injury severity, neurological level, energy
      and age as predictor and was compared to a more complex model considering all 11
      predictors mentioned above The models built using 4 and 11 predictors were found
      to explain 51.4% and 62.3% of the variance of the Spinal Cord Independence
      Measure total score after validation, respectively. The severity of the
      neurological deficit at admission was found to be the most important predictor.
      Other important predictors were the Injury Severity Score, age, neurological
      level and delay prior to surgery. Regression trees offer promising performances
      for predicting the functional outcome after a traumatic spinal cord injury. It
      could help to determine the number and type of predictors leading to a prediction
      model of the functional outcome that can be used clinically in the future.

PMID- 29065783
TI  - Efficacy of emergency exploratory laparotomy in incarcerated obturator hernia.
AB  - BACKGROUND: Incarcerated obturator hernia (IOH) is a scarce type of acute
      surgical disease, but the mortality rate is the highest in abdominal hernias. The
      aim of this study was to evaluate the efficacy of emergency exploratory
      laparotomy (EEL) in treating incarcerated obturator hernia (IOH). METHODS: We
      conducted a retrospective study of 12 female patients with IOH underwent EEL
      between January 2014 and March 2016. The variables which included patient
      characteristics, findings of CT, operative time, postoperative complications,
      length of hospital stay, ICU admission rate, 30-day readmission rate and
      mortality were analyzed. RESULTS: The age of patients was 82.5 +/- 4.2 years and
      the median body mass index (BMI) was 20.6 kg/m2 (IQR, 18.7-21.5 kg/m2). There
      were 10 patients (83.3%) underwent partial intestinal resection due to partial
      small bowel necrosis or perforation. The total operation time was 85.7 +/- 8.7
      min. The time to initiation of a soft diet was 3.9 +/- 0.7 days and the median
      length of stay was 15.0 days (IQR, 14.0-17.5 days), respectively. CONCLUSIONS:
      The EEL is a clinically safe and necessary choice for early diagnosis and
      treatment in IOH. EEL may improve the curative effect of IOH significantly.

PMID- 29065785
TI  - Corrigendum to "Enhancing the alignment of the preclinical and clinical stroke
      recovery research pipeline: Consensus-based core recommendations from the Stroke
      Recovery and Rehabilitation Roundtable translational working group".

PMID- 29065784
TI  - Effect of vancomycin initial dosing on time to systemic inflammatory response
      syndrome resolution in patients with methicillin-resistant Staphylococcus aureus
      bacteremia.
AB  - Current guidelines suggest using vancomycin-loading doses for complicated
      infections despite a lack of evidence to support this practice. To address this
      gap, we performed a single-centre cohort study of 124 patients with sepsis due to
      methicillin-resistant Staphylococcus aureus bacteremia. Patients were allocated
      into two groups based on initial dose of vancomycin, <20 mg/kg or >=20 mg/kg, and
      evaluated for time to resolution of systemic inflammatory response syndrome
      (SIRS). Among a cohort of 124 patients, 87 received vancomycin initial doses <20
      mg/kg and 37 received >=20 mg/kg. The median time to SIRS resolution was 109 h in
      the <20 mg/kg group compared to 67 h in the >=20 mg/kg group. Cox proportional
      hazard modelling showed a faster resolution of SIRS in the >=20 mg/kg group (HR =
      1.72[1.09-2.73]). Vancomycin initial doses of >=20 mg/kg led to faster resolution
      of SIRS although further studies are needed to evaluate the safety and efficacy
      of this approach.

PMID- 29065786
TI  - Severe liver toxicity in a chronic myeloid leukemia patient probably induced by a
      drug interaction between imatinib and sertraline.
AB  - Our objective is to describe a chronic myeloid leukemia patient with a severe
      liver toxicity likely due to a drug-drug interaction between imatinib and
      sertraline. The patient started treatment with sertraline three months after
      starting imatinib. From the beginning of sertraline treatment, the patient
      developed vomiting, and five weeks later she developed a severe hepatic failure
      and was admitted to the hospital. The Naranjo nomogram showed a probable
      correlation between this adverse effect and the interaction between imatinib and
      sertraline. This interaction is extremely rare and the mechanism of action is not
      clear; it could be a mix of pharmacokinetic and pharmacodynamic processes. To our
      knowledge, this is the first case in medical literature of a severe liver
      toxicity due to an interaction between imatinib and sertraline. This interaction
      is also not described in the main secondary data sources, such as Lexicomp(r) and
      Micromedex(r). However, due to the severity of this event, the hepatic function
      should be carefully monitored in patients treated with imatinib and sertraline.

PMID- 29065787
TI  - Preconditioning potential of purmorphamine: a hedgehog activator against
      ischaemic reperfusion injury in ovariectomised rat heart.
AB  - OBJECTIVE: The present study was been designed to investigate the role and
      pharmacological potential of hedgehog in oestrogen-deficient rat heart. METHODS:
      Oestrogen deficiency was produced in female Wistar rats by the surgical removal
      of both ovaries and these animals were used four weeks later. Isolated rat heart
      was subjected to 30 min ischaemia followed by 120 min of reperfusion (I/R). The
      heart was subjected to pharmacological preconditioning with the hedgehog agonist
      purmorphamine (1MUM) and GDC-0449, a hedgehog antagonist, in the last episode of
      reperfusion before I/R. Myocardial infarction was assessed in terms of the
      increase in lactate dehydrogenase (LDH), creatinine kinase-MB (CK-MB),
      myeloperoxidase (MPO) level and infarct size (triphenyltetrazolium chloride
      staining). Immunohistochemistry analysis was done for the assessment of tumour
      necrosis factor (TNF)-alpha level in cardiac tissue. eNOS expression was
      estimated by rt-PCR. RESULTS: Pharmacological preconditioning with purmorphamine
      significantly attenuated I/R-induced myocardial infarction, TNF-alpha, MPO level
      and release of LDH and CK-MB compared to the I/R control group. However, GDC-0449
      prevented the ameliorative preconditioning effect of estradiol. CONCLUSION: It
      may be concluded that the hedgehog agonist purmorphamine prevents the
      ovariectomised heart from ischaemic reperfusion injury.

PMID- 29065788
TI  - Walking speed is not the best outcome to evaluate the effect of robotic assisted
      gait training in people with motor incomplete Spinal Cord Injury: A Systematic
      Review with meta-analysis.
AB  - Context While there are previous systematic reviews on the effectiveness of the
      use of robotic-assisted gait training (RAGT) in people with spinal cord injuries
      (SCI), as this is a dynamic field, new studies have been produced that are now
      incorporated on this systematic review (SR) with meta-analysis, updating the
      available evidence on this area. Objective To synthesise the available evidence
      on the use of RAGT, to improve gait, strength and functioning. Methods SR and
      meta-analysis following the Cochrane Handbook for Systematic Reviews of
      Interventions were implemented. Cochrane Injuries Group Specialized Register,
      PubMed, MEDLINE, EMBASE, CINAHL, ISIWeb of Science (SCIEXPANDED) databases were
      reviewed for the period 1990 to December 2016. Three researchers independently
      identified and categorized trials; 293 studies were identified, 273 eliminated;
      remaining 15 randomized clinical trials (RCT) and five SR. Six studies had
      available data for meta-analysis (222 participants). Results The pooled mean
      demonstrated a beneficial effect of RAGT for WISCI, FIM-L and LEMS (3.01, 2.74
      and 1.95 respectively), and no effect for speed. Conclusions The results show a
      positive effect in the use of RAGT. However, this should be taken carefully due
      to heterogeneity of the studies, small samples and identified limitations of some
      of the included trials. These results highlight the relevance of implementing a
      well-designed multicenter RCT powered enough to evaluate different RAGT
      approaches.

PMID- 29065789
TI  - Images in Vascular Medicine: Quantitative digital subtraction angiography during
      type B chronic aortic dissection endovascular repair.

PMID- 29065790
TI  - Surgical and endovascular venous arterialization for treatment of critical limb
      ischaemia.
AB  - Patients with critical limb ischaemia have a poor life expectancy. Aggressive
      revascularization is accepted in order to preserve their independence in the
      final phase of their lives. Bypass surgery and more recently endovascular
      interventions with angioplasty and stenting have become the treatment of choice
      to prevent amputation and to resolve pain. However, as many as 20 % of patients
      with critical limb ischaemia are unsuitable candidates for a vascular
      intervention because of extensive occlusions of outflow in the crural and pedal
      vessels. Such "no-option critical limb ischaemia" may be treated with venous
      arterialization. In the present review, we discuss the history of the venous
      arterialization procedure, the mechanisms, the different techniques, and
      complications of venous arterialization.

PMID- 29065791
TI  - Epithelioid Hemangioma of the Thoracic Spine: A Case Report and Review of the
      Literature.
AB  - CONTEXT: Osseous epithelioid hemangioma is uncommon, and reports of epithelioid
      hemangiomas of the spine are especially rare. STUDY DESIGN: Case report.
      FINDINGS: A 43-year-old male was referred to our department with progressive gait
      disturbance. CT scans showed a lucent mass in the vertebral body at the T3 level.
      MRI of the thoracic spine showed a strongly enhanced mass compressing the spinal
      cord. The patient underwent laminectomy from T2 to T4, debulking of the tumor,
      and posterior fusion from T1 to T5. After the operation, the patient's
      neurological status improved significantly, and he was able walk without
      assistance. Histological examination determined that the tumor was an epithelioid
      hemangioma. The patient was treated with 40 Gy radiation for local control of the
      tumor. The patient could walk without difficulty 12 months after the surgery.
      CONCLUSION: This is a rare example of an epithelioid hemangioma that developed in
      the thoracic spine and compressed the spinal cord, and was treated successfully.

PMID- 29065792
TI  - Comparison of ambulatory blood pressure monitoring and office blood pressure
      measurements in obese children and adolescents.
AB  - BACKGROUND: Obesity in adults has been related to hypertension and abnormal
      nocturnal dipping of blood pressure, which are associated with poor
      cardiovascular and renal outcomes. Here, we aimed to resolve the relationship
      between the degree of obesity, the severity of hypertension and dipping status on
      ambulatory blood pressure in obese children. METHODS: A total 72 patients with
      primary obesity aged 7 to 18 years (mean: 13.48 +/- 3.25) were selected. Patients
      were divided into three groups based on body mass index (BMI) Z-score. Diagnosis
      and staging of ambulatory hypertension based on 24-h blood pressure measurements,
      obtained from ambulatory blood pressure monitoring. RESULTS: Based on our
      ambulatory blood pressure data, 35 patients (48.6%) had hypertension, 7 (20%) had
      ambulatory prehypertension, 21 (60%) had hypertension, and 7 patients (20%) had
      severe ambulatory hypertension. There was a significant relationship between
      severity of hypertension and the degree of obesity (p < 0.05). Thirty-one
      patients (88.6%) had isolated nighttime hypertension, and 53 patients (73.6%)
      were non-dippers. All systolic blood pressure results and loads were similar
      between groups. Diastolic and mean arterial blood pressure levels during the
      night, diastolic blood pressure loads, and heart rate during the day were
      significantly higher in Group 3 (p < 0.05). Nocturnal non-dipping was not
      associated with severity of obesity. CONCLUSION: Obesity was associated with
      severity of hypertension, higher diastolic blood pressure at night, mean arterial
      pressure at night, diastolic blood pressure loads and heart rate at day. Increase
      in BMI Z-score does not a significant impact on daytime blood pressure and
      nocturnal dipping status.

PMID- 29065793
TI  - The three-dimensional shapes of underground coal miners' feet do not match the
      internal dimensions of their work boots.
AB  - Mining work boots provide an interface between the foot and the ground,
      protecting and supporting miners' feet during lengthy coal mining shifts.
      Although underground coal miners report the fit of their work boots as reasonable
      to good, they frequently rate their boots as uncomfortable, suggesting that there
      is a mismatch between the shape of their feet and their boots. This study aimed
      to identify whether dimensions derived from the three-dimensional scans of 208
      underground coal miners' feet (age 38.3 +/- 9.8 years) differed from the internal
      dimensions of their work boots. The results revealed underground coal miners wore
      boots that were substantially longer than their feet, possibly because boots
      available in their correct length were too narrow. It is recommended boot
      manufacturers reassess the algorithms used to create boot lasts, focusing on
      adjusting boot circumference at the instep and heel relative to increases in foot
      length. Practitioner Summary: Fit and comfort ratings suggest a mismatch between
      the shape of underground coal miners' feet and their boots exists. This study
      examined whether three-dimensional scans of 208 miners' feet differed from their
      boot internal dimensions. Miners wore boots substantially longer than their feet,
      possibly due to inadequate width.

PMID- 29065794
TI  - Prolonged exposure of resveratrol induces reactive superoxide species-independent
      apoptosis in murine prostate cells.
AB  - Nitric oxide, a signaling molecule, inhibits mitochondrial respiration by binding
      with cytochrome c oxidase, resulting in elevated production of reactive
      superoxide species (reactive oxygen and nitrogen) in the mitochondria and
      increased susceptibility to cell death. Generation of mitochondrial superoxide
      species can be suppressed by natural compounds such as resveratrol, a dietary
      polyphenol found in the skin of red fruits. In various cancer cells, resveratrol
      shows anti-oxidant and cancer preventive properties. Since, the effect of
      resveratrol on reactive superoxide species-independent apoptosis in prostate
      cancer cells is not well illustrated; therefore, we investigated this phenomenon
      in TRAMP murine prostate cancer cells. To accomplish this, TRAMP cells were
      incubated with resveratrol, resveratrol + DETA-NONOate, DETA-NONOate (nitric
      oxide donor), resveratrol + L-NMMA, or L-NMMA (nitric oxide inhibitor) for 48 h,
      and reactive superoxide species in the mitochondria and culture supernatant were
      measured. In addition, the mitochondrial membrane potential, cell viability,
      expression of apoptotic markers (Bax and Bcl2), gamma-H2A.x, p53, and caspase-3
      was determined. We found that resveratrol suppressed reactive superoxide species
      such as reactive oxygen species in the mitochondria and nitric oxide in culture
      supernatant when compared to the DETA-NONOate treatment and disrupted the
      mitochondrial membrane potential. Resveratrol also reduced cell viability,
      altered the expression of apoptotic markers (Bax and Bcl2), and increased
      expression of gamma-H2A.x (indicative marker of DNA fragmentation) and p53 (a
      critical DNA damage response protein). However, there was no appreciable
      modulation of the caspase-3. Therefore, our data suggest that resveratrol induces
      superoxide species-independent apoptosis and may act as a therapeutic agent
      against prostate cancer.

PMID- 29065795
TI  - Antifilarial activity of caffeic acid phenethyl ester on Brugia pahangi in vitro
      and in vivo.
AB  - Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms
      such as Wuchereria bancrofti, Brugia malayi and B. timori, which are transmitted
      by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and
      lack activity against adult worms. This set back, poses a challenge for the
      control and elimination of filariasis. Thus, in this study the activities of
      caffeic acid phenethyl ester (CAPE) against the filarial worm B. pahangi and its
      bacterial endosymbiont, Wolbachia were evaluated. Different concentrations (2, 5,
      10, 15, 20 MUg/ml) of CAPE were used to assess its effects on motility, viability
      and microfilarial (mf) production of B. pahangi in vitro. Anti-Wolbachial
      activity of CAPE was measured in worms by quantification of Wolbachial wsp gene
      copy number using real-time polymerase chain reaction. Our findings show that
      CAPE was found to significantly reduce adult worm motility, viability, and mf
      release both in vitro and in vivo. 20 MUg/ml of CAPE halts the release of mf in
      vitro by day 6 of post treatment. Also, the number of adult worms recovered in
      vivo were reduced significantly during and after treatment with 50 mg/kg of CAPE
      relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR
      based on the Wolbachia ftsZ gene revealed a significant reduction in Wolbachia
      copy number upon treatment. Anti-Wolbachia and antifilarial properties of CAPE
      require further investigation as an alternative strategy to treat LF.

PMID- 29065797
TI  - Self-contained, low-cost Body-on-a-Chip systems for drug development.
AB  - Integrated multi-organ microphysiological systems are an evolving tool for
      preclinical evaluation of the potential toxicity and efficacy of drug candidates.
      Such systems, also known as Body-on-a-Chip devices, have a great potential to
      increase the successful conversion of drug candidates entering clinical trials
      into approved drugs. Systems, to be attractive for commercial adoption, need to
      be inexpensive, easy to operate, and give reproducible results. Further, the
      ability to measure functional responses, such as electrical activity, force
      generation, and barrier integrity of organ surrogates, enhances the ability to
      monitor response to drugs. The ability to operate a system for significant
      periods of time (up to 28 d) will provide potential to estimate chronic as well
      as acute responses of the human body. Here we review progress towards a self
      contained low-cost microphysiological system with functional measurements of
      physiological responses. Impact statement Multi-organ microphysiological systems
      are promising devices to improve the drug development process. The development of
      a pumpless system represents the ability to build multi-organ systems that are of
      low cost, high reliability, and self-contained. These features, coupled with the
      ability to measure electrical and mechanical response in addition to chemical or
      metabolic changes, provides an attractive system for incorporation into the drug
      development process. This will be the most complete review of the pumpless
      platform with recirculation yet written.

PMID- 29065796
TI  - Circadian hormone control in a human-on-a-chip: In vitro biology's ignored
      component?
AB  - Organs-on-Chips (OoCs) are poised to reshape dramatically the study of biology by
      replicating in vivo the function of individual and coupled human organs. Such
      microphysiological systems (MPS) have already recreated complex physiological
      responses necessary to simulate human organ function not evident in two
      dimensional in vitro biological experiments. OoC researchers hope to streamline
      pharmaceutical development, accelerate toxicology studies, limit animal testing,
      and provide new insights beyond the capability of current biological models.
      However, to develop a physiologically accurate Human-on-a-Chip, i.e., an MPS
      homunculus that functions as an interconnected, whole-body, model organ system,
      one must couple individual OoCs with proper fluidic and metabolic scaling. This
      will enable the study of the effects of organ-organ interactions on the
      metabolism of drugs and toxins. Critical to these efforts will be the
      recapitulation of the complex physiological signals that regulate the endocrine,
      metabolic, and digestive systems. To date, with the exception of research focused
      on reproductive organs on chips, most OoC research ignores homuncular endocrine
      regulation, in particular the circadian rhythms that modulate the function of all
      organ systems. We outline the importance of cyclic endocrine regulation and the
      role that it may play in the development of MPS homunculi for the pharmacology,
      toxicology, and systems biology communities. Moreover, we discuss the critical
      end-organ hormone interactions that are most relevant for a typical coupled-OoC
      system, and the possible research applications of a missing endocrine system
      MicroFormulator (MES-uF) that could impose biological rhythms on in vitro models.
      By linking OoCs together through chemical messenger systems, advanced
      physiological phenomena relevant to pharmacokinetics and pharmacodynamics studies
      can be replicated. The concept of a MES-uF could be applied to other standard
      cell-culture systems such as well plates, thereby extending the concept of
      circadian hormonal regulation to much of in vitro biology. Impact statement
      Historically, cyclic endocrine modulation has been largely ignored within in
      vitro cell culture, in part because cultured cells typically have their media
      changed every day or two, precluding hourly adjustment of hormone concentrations
      to simulate circadian rhythms. As the Organ-on-Chip (OoC) community strives for
      greater physiological realism, the contribution of hormonal oscillations toward
      regulation of organ systems has been examined only in the context of reproductive
      organs, and circadian variation of the breadth of other hormones on most organs
      remains unaddressed. We illustrate the importance of cyclic endocrine modulation
      and the role that it plays within individual organ systems. The study of cyclic
      endocrine modulation within OoC systems will help advance OoC research to the
      point where it can reliably replicate in vitro key regulatory components of human
      physiology. This will help translate OoC work into pharmaceutical applications
      and connect the OoC community with the greater pharmacology and physiology
      communities.

PMID- 29065800
TI  - Fatty acid transporter expression and regulation is impaired in placental
      macrovascular endothelial cells in obese women.
AB  - OBJECTIVE: Fetal fatty acid (FA) delivery is ultimately controlled by placental
      transport. Focus has been the maternal-placental interface, but regulation at the
      feto-placental interface is unknown. METHODS: Placental macrovascular endothelial
      cells (EC) (n = 4/group) and trophoblasts (TB) (n = 5/group) were isolated from
      lean (pregravid BMI <25 kg/m2) and obese (body mass index (BMI) > 30) women.
      Fatty acid transporters FAT/CD36, FABPpm, FATP4, FABP 3, 4 and 5, PLIN2 and
      PPARalpha, delta, gamma expression, was measured in EC and TB. Transporter
      response to 24 h palmitate (PA) was assessed. RESULTS: mRNA expression of FABP3,
      4, 5 and PPARgamma was 2- to 3-fold reduced in EC of obese versus lean women (p <
      .03), but not in TB. Protein level of FABPpm was 20% lower in obese (p < .05).
      Palmitate (PA) up-regulated CD36, FABP3, FABP4, and PLIN2 gene expression by 3-
      to 4-fold in lean but not obese EC (p < .05), while PA increased FABP4 and PLIN2
      in lean and obese TB, and FABP5 in lean (p < .05) EC. PA exposure up-regulated
      peroxisome proliferator activated receptors (PPARs) 2-fold in lean and obese EC
      (p < .05), but not in TB. CONCLUSIONS: In obese women, FA transporter expression
      is lower in placental EC, but not TB, and less sensitive to saturated FA,
      compared to lean women. FA transport may be regulated at the feto-placental
      interface.

PMID- 29065801
TI  - Liver resection in pregnancy.

PMID- 29065798
TI  - Microphysiologic systems in female reproductive biology.
AB  - Microphysiologic systems (MPS), including new organ-on-a-chip technologies,
      recapitulate tissue microenvironments by employing specially designed tissue or
      cell culturing techniques and microfluidic flow. Such systems are designed to
      incorporate physiologic factors that conventional 2D or even 3D systems cannot,
      such as the multicellular dynamics of a tissue-tissue interface or physical
      forces like fluid sheer stress. The female reproductive system is a series of
      interconnected organs that are necessary to produce eggs, support embryo
      development and female health, and impact the functioning of non-reproductive
      tissues throughout the body. Despite its importance, the human reproductive tract
      has received less attention than other organ systems, such as the liver and
      kidney, in terms of modeling with MPS. In this review, we discuss current gaps in
      the field and areas for technological advancement through the application of MPS.
      We explore current MPS research in female reproductive biology, including
      fertilization, pregnancy, and female reproductive tract diseases, with a focus on
      their clinical applications. Impact statement This review discusses existing
      microphysiologic systems technology that may be applied to study of the female
      reproductive tract, and those currently in development to specifically
      investigate gametes, fertilization, embryo development, pregnancy, and diseases
      of the female reproductive tract. We focus on the clinical applicability of these
      new technologies in fields such as assisted reproductive technologies, drug
      testing, disease diagnostics, and personalized medicine.

PMID- 29065803
TI  - Mechlorethamine, vincristine, melphalan and prednisolone rescue chemotherapy
      protocol for resistant feline lymphoma.
AB  - Objectives The goals of this retrospective study were to evaluate the use of
      mechlorethamine, vincristine, melphalan and prednisolone (MOMP) chemotherapy for
      rescue of feline lymphoma, to describe the protocol's toxicity and to determine
      prognostic indicators for progression-free survival. Methods The medical records
      of 12 cats treated with MOMP chemotherapy at the University of Tennessee
      Veterinary Medical Center between 2007 and 2017 were evaluated. Parameters
      assessed included lymphoma cell size, anatomical location, number of previous
      chemotherapy drugs and number of previous rescue protocols received. Chemotherapy
      related toxicity was also described. Results Seven of 12 cats responded to this
      rescue protocol. Three cats experienced complete response and four cats achieved
      partial response for a median duration of 39 days (range 14-345 days). Cats that
      achieved complete response had a significantly longer median progression-free
      survival than cats that did not respond to treatment. Five of 12 cats developed
      hematologic toxicity (neutropenia) and one cat developed gastrointestinal
      toxicity. Toxicity was mild in most cases; no cats needed to be hospitalized.
      Neutropenia was associated with increased progression-free survival. Conclusions
      and relevance MOMP is a safe and effective rescue chemotherapy protocol for cats
      with relapsing and refractory lymphoma.

PMID- 29065802
TI  - Transabdominal recordings of fetal heart rate in extremely small fetuses.
AB  - INTRODUCTION: As part of the fetal assessment for the Safe Passage Study, we
      recorded raw data of the fetal ECG via five maternal abdominal wall electrodes
      from 20 weeks to 23 weeks 6 days' gestation. MATERIALS: For this study were
      extracted and analyzed the FHR patterns from the stored raw data in 16
      stillbirths where the fetus weighed less than 1000 g and where autopsy was
      performed. RESULTS: Birth weights ranged from 190 to 970 g. The proportion FHR
      signal loss ranged from 0.3% to 21.1%. In the smallest fetus the heart weighed
      1.3 g, yet the FHR signal loss was only 0.9%.

PMID- 29065799
TI  - Fitting tissue chips and microphysiological systems into the grand scheme of
      medicine, biology, pharmacology, and toxicology.
AB  - Microphysiological systems (MPS), which include engineered organoids (EOs),
      single organ/tissue chips (TCs), and multiple organs interconnected to create
      miniature in vitro models of human physiological systems, are rapidly becoming
      effective tools for drug development and the mechanistic understanding of tissue
      physiology and pathophysiology. The second MPS thematic issue of Experimental
      Biology and Medicine comprises 15 articles by scientists and engineers from the
      National Institutes of Health, the IQ Consortium, the Food and Drug
      Administration, and Environmental Protection Agency, an MPS company, and
      academia. Topics include the progress, challenges, and future of organs-on-chips,
      dissemination of TCs into Pharma, children's health protection, liver zonation,
      liver chips and their coupling to interconnected systems, gastrointestinal MPS,
      maturation of immature cardiomyocytes in a heart-on-a-chip, coculture of multiple
      cell types in a human skin construct, use of synthetic hydrogels to create EOs
      that form neural tissue models, the blood-brain barrier-on-a-chip, MPS models of
      coupled female reproductive organs, coupling MPS devices to create a body-on-a
      chip, and the use of a microformulator to recapitulate endocrine circadian
      rhythms. While MPS hardware has been relatively stable since the last MPS
      thematic issue, there have been significant advances in cell sourcing, with
      increased reliance on human-induced pluripotent stem cells, and in
      characterization of the genetic and functional cell state in MPS bioreactors.
      There is growing appreciation of the need to minimize perfusate-to-cell-volume
      ratios and respect physiological scaling of coupled TCs. Questions asked by drug
      developers are followed by an analysis of the potential value, costs, and needs
      of Pharma. Of highest value and lowest switching costs may be the development of
      MPS disease models to aid in the discovery of disease mechanisms; novel compounds
      including probes, leads, and clinical candidates; and mechanism of action of drug
      candidates. Impact statement Microphysiological systems (MPS), which include
      engineered organoids and both individual and coupled organs-on-chips and tissue
      chips, are a rapidly growing topic of research that addresses the known
      limitations of conventional cellular monoculture on flat plastic - a well
      perfected set of techniques that produces reliable, statistically significant
      results that may not adequately represent human biology and disease. As reviewed
      in this article and the others in this thematic issue, MPS research has made
      notable progress in the past three years in both cell sourcing and
      characterization. As the field matures, currently identified challenges are being
      addressed, and new ones are being recognized. Building upon investments by the
      Defense Advanced Research Projects Agency, National Institutes of Health, Food
      and Drug Administration, Defense Threat Reduction Agency, and Environmental
      Protection Agency of more than $200 million since 2012 and sizable corporate
      spending, academic and commercial players in the MPS community are demonstrating
      their ability to meet the translational challenges required to apply MPS
      technologies to accelerate drug development and advance toxicology.

PMID- 29065804
TI  - Recurrence of spinal anaplastic astrocytoma in a cat after surgical treatment and
      long-term follow-up.

PMID- 29065806
TI  - "Mourning With the Morning Bell": An Examination of Secondary Educators'
      Attitudes and Experiences in Managing the Discourse of Death in the Classroom.
AB  - A plethora of research exists about death and dying, particularly with regard to
      the prescriptive strategy on how teachers should address death in their
      classrooms. However, there is a gap in the literature about teachers' perceived
      preparedness to discuss a student's death in their classrooms. The following
      qualitative study used focus groups to explore teachers' experiences with and
      beliefs about death, dying, coping, student death, and preparedness to address
      student death in the classroom. Data were transcribed and thematically analyzed.
      Themes and subthemes for all research questions are presented and explained; some
      themes explored include teachers' views of death, death versus dying, initial and
      long-term coping, difficulties in addressing student death, the teachers' role
      after a student's death, feelings of being prepared versus unprepared to address
      student death in the classroom.

PMID- 29065807
TI  - Prospective memory in children with attention deficit hyperactivity disorder: a
      review.
AB  - OBJECTIVE: The objective of the paper is to synthesize the research on
      prospective memory (PM) in children with attention-deficit/hyperactivity disorder
      (ADHD). METHOD: Research on PM and ADHD in youth was synthesized according to the
      PRISMA guidelines and a summary of the types of PM deficits typically seen in
      these children, as well as the methods currently available to assess and treat
      these deficits is provided. Suggestions on ways to better manage PM deficits in
      children's everyday lives are also discussed. RESULTS: Six studies have
      investigated PM in children with ADHD. The majority of these studies found a
      deficit in time-based PM, but not event-based PM. The mechanisms underlying this
      deficit, however, are still unknown. There are currently no specific measures
      available to clinically assess PM in children and there are no specific evidence
      based interventions available that specifically target PM deficits in children
      with ADHD. CONCLUSION: Remediation strategies aimed at compensating for these PM
      deficits in daily life may be most useful. Nevertheless, more research is
      necessary to better understand PM in children with ADHD.

PMID- 29065808
TI  - Childhood abuse in adults in primary care: Empirical findings and clinical
      implications.
AB  - In the healthcare setting, adult patients with histories of childhood abuse are
      of significant concern and are frequently encountered in the primary care
      setting. However, there is a dearth of studies investigating the relationships
      between psychopathology, overall health, healthcare utilization, physician
      ratings of patient difficulty, and childhood abuse. The present study examines
      these relationships in primary care patients with (N = 45) and without (N = 129)
      histories of childhood abuse (physical, sexual, and both). Findings revealed that
      adult patients with histories of childhood abuse generally scored significantly
      higher on measures of psychopathology, emergency room use, and doctor-patient
      relationship difficulty, and lower on a measure of mental and physician-rated
      physical health. In a multiple regression analysis, income and a history of
      childhood sexual abuse significantly predicted overall mental health. In a second
      multiple regression analysis, income, depression, somatization, borderline
      personality disorder, and difficult doctor-patient relationship ratings
      significantly predicted physician-rated physical health. Overall, these findings
      suggest that a history of childhood abuse is associated with a host of negative
      health outcomes. Findings also suggest that negative feelings about a patient may
      help physicians identify patients with histories of childhood abuse. It is
      especially important for physicians to routinely include an assessment of
      childhood abuse during the psychosocial portion of the medical interview or
      through screening instruments.

PMID- 29065805
TI  - Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor
      Imaging Study from the NCAA-DoD CARE Consortium.
AB  - Sports-related concussion (SRC) is an important public health issue. Although
      standardized assessment tools are useful in the clinical management of acute
      concussion, the underlying pathophysiology of SRC and the time course of
      physiological recovery after injury remain unclear. In this study, we used
      diffusion tensor imaging (DTI) to detect white matter alterations in football
      players within 48 h after SRC. As part of the NCAA-DoD CARE Consortium study of
      SRC, 30 American football players diagnosed with acute concussion and 28 matched
      controls received clinical assessments and underwent advanced magnetic resonance
      imaging scans. To avoid selection bias and partial volume effects, whole-brain
      skeletonized white matter was examined by tract-based spatial statistics to
      investigate between-group differences in DTI metrics and their associations with
      clinical outcome measures. Mean diffusivity was significantly higher in brain
      white matter of concussed athletes, particularly in frontal and subfrontal long
      white matter tracts. In the concussed group, axial diffusivity was significantly
      correlated with the Brief Symptom Inventory and there was a similar trend with
      the symptom severity score of the Sport Concussion Assessment Tool. In addition,
      concussed athletes with higher fractional anisotropy performed better on the
      cognitive component of the Standardized Assessment of Concussion. Overall, the
      results of this study are consistent with the hypothesis that SRC is associated
      with changes in white matter tracts shortly after injury, and these differences
      are correlated clinically with acute symptoms and functional impairments.

PMID- 29065809
TI  - Teaching resident physicians to work with the previously incarcerated patient.
AB  - Over 2 million adults in the United States are incarcerated and over 650,000
      return to the community each year. This disparate population is known to have an
      elevated burden of chronic disease and lower socioeconomic status. Medical
      residency training about care for incarcerated or previously incarcerated
      patients is significantly lacking in the United States. Curriculum can be
      developed and implemented in residency programs to help physicians learn how to
      work with this population, be sensitive to their unique needs, and achieve
      positive health outcomes. This article describes a method for "educating the
      educators" based on a workshop presented at a peer-reviewed national conference
      during the fall of 2016. Attendees participated in exercises addressing
      assumptions, expectations, bias, and worldview and increased their ability for
      self-reflection when interacting with patients who are or have experienced
      incarceration. In this session, strategies were identified that engaged the
      patient with the goal to aid in patient retention and compliance. Future steps
      include development of a formal curriculum for training in this area,
      incorporation into existing community medicine rotations or electives, and
      establishment of structured transition clinics where residents can be exposed to
      this population on a more regular basis and improve their overall health
      outcomes.

PMID- 29065810
TI  - Teaching health-care trainees empathy and homelessness IQ through service
      learning, reflective practice, and altruistic attribution.
AB  - This article describes a novel inter-professional curriculum designed to address
      the needs of homeless patients in a Midwestern region of the United States which
      has high rates of poverty. The curriculum is intended for healthcare trainees
      coming from undergraduate pre-medical programs, nursing, pharmacy, social work,
      clinical psychology, medical school and post-graduate medical training in family
      medicine, medicine-pediatrics, and psychiatry. The clinical component is
      specifically designed to reach destitute patients and the curriculum is
      structured to reverse commonly held myths about homelessness among the trainees,
      thereby improving their Homelessness Information Quotient, the ability to more
      fully understand homelessness. Participants across all disciplines and
      specialties have shown greater empathy and helper behavior as determined by
      qualitative measures. Learners have also developed a greater understanding of
      health-care systems allowing them to more consistently address social
      determinants of health identified by the authors as their Disparity Information
      Quotient. This article outlines the process of initiating a homeless service
      program, a curriculum for addressing common myths about homelessness and the
      effective use of narrative methods, relational connections, and reflective
      practice to enable trainees to process their experience and decrease burnout by
      focusing on the value of altruism and finding meaning in their work.

PMID- 29065811
TI  - Educational strategies for overcoming health care disparities.

PMID- 29065812
TI  - Grant writing: Moving from generating ideas to applying to grants that matter.
AB  - There is an extraordinary burden placed upon the healthcare system and people as
      a result of health disparities that exist within the United States. If there is
      going to be a concerted effort to develop innovative strategies to reduce health
      disparities, input from the community and behavioral scientists can and should be
      included in this approach and narrative. Grant writing provides one vehicle to
      express the narrative and to provide a means to fund research and programs within
      clinic-based and community settings. This paper describes a four-step inquiry
      process to guide healthcare professionals with varying degrees of clinical and
      scholarship interests through the grant writing process. They include: (1) Why
      write grants (motivations), (2) what is the area of focus? (Interests), (3) whom
      should be on the project? (partnerships), and (4) what needs to happen next to
      move the idea forward? (actions) The complexity of psychosocial issues means that
      behavioral science is well suited to develop both hypotheses-driven and
      phenomenological research to understand bio-psycho-social health issues. Grant
      writing does not need to be mysterious or daunting. It can provide a means to an
      end, not only to fund research but also as a means to an end of health
      disparities.

PMID- 29065813
TI  - Enter as an outsider: Teaching organizational humility.
AB  - The concept of cultural humility acknowledges the enormous task of becoming
      culturally competent by encouraging curiosity about the context within which
      others live. For physicians, this includes curiosity about the organizations in
      which they work as Outsiders in settings such as a new hospital or patients'
      homes. However, efforts to train healthcare professionals in cultural competence
      are often de-emphasized due to the pressure learners feel to acquire Medical
      Knowledge and clinical skills. Little time is devoted to address the significance
      of cultural humility for fully appreciating the experiences of others. Efforts to
      educate physicians-in-training about the cultural aspects of care require
      innovative approaches that help them recognize bias without provoking
      defensiveness. Enter as an Outsider is a highly focused activity which fosters a
      culturally humble approach to an often neglected problem, organizational bias.
      This article describes how cultural humility is explained to learners and small
      group activities are used to explore the thoughts and feelings of an
      organization's Insiders and Outsiders. This program relies on instructor self
      disclosure to facilitate learning and on a video vignette from popular-culture
      media to illustrate being an Outsider in a healthcare setting. Participants in
      this training have improved their ability to recognize when they are Outsiders
      where they provide care. They have developed a better understanding that cultural
      humility in organizations is a gateway to providing quality care. They have begun
      the process of committing to respectfully learn from the organization's Insiders.

PMID- 29065815
TI  - Management of pain in TMD patients: Bio-oxidative ozone therapy versus occlusal
      splints.
AB  - OBJECTIVE: To compare the effects of bio-oxidative ozone application with
      occlusal splints in temporomandibular disorder (TMD) patients with pain. METHODS:
      Forty participants were selected after the diagnosis of TMD and randomly divided
      into two groups: ozone group (OG, n = 20) and occlusal splint group (OCSG, n =
      20). Ozone was applied to patients three times per week, for a total of six
      sessions. Patients in the OCSG were instructed to use occlusal splints every
      night over a period of four weeks. RESULTS: Mandibular movements showed
      significant differences for the time factor in OG and OCSG. Pressure pain
      thresholds of the temporal and masseter muscles at follow-up were significantly
      higher in the OCSG group. Both treatments statistically decreased the visual
      analog scale (VAS) scores. However, no statistically significant difference was
      observed between groups after the application of treatments. DISCUSSION: Occlusal
      splint treatment is still the gold treatment modality for objective pain relief
      in patients with TMD pain.

PMID- 29065814
TI  - A commitment to health equity: Reflections on why; One journey toward how.
AB  - Many health care practitioners and educators feel stymied as to how to address
      the pervasive and persistent problem of health care disparities between racial
      and ethnic groups. The closing plenary for the 37th Forum for Behavioral Science
      in Family Medicine held in September 2016 reminded participants of the urgent
      need to attend to health inequities and provided both a theoretical framework as
      well as some sample resources for where to begin.

PMID- 29065817
TI  - What is the real scope of waste management?

PMID- 29065816
TI  - Attentional modulation of early visual areas.
AB  - This special issue of Cognitive Neuroscience focuses on the debate regarding
      whether spatial attention can rapidly modulate the event-related potential (ERP)
      C1 component, which reflects the initial feedforward signal in V1. A discussion
      paper by Baumgartner, Graulty, Hillyard, and Pitts (this issue) included an
      empirical experiment that failed to replicate the significant C1 attention
      effects of Kelly, Gomez-Ramirez, and Foxe. Commentaries were received by Ding
      (this issue), Klein (this issue), Pourtois, Rossi, Vuilleumier, and Rauss (this
      issue), Kelly and Mohr (this issue), Slagter, Alilovic, and Van Gaal (this
      issue), and Fu (this issue). The author response highlighted that C1 attention
      effects may be obtained in only limited conditions, considered problems of
      investigating C1 attention effects, and proposed future strategies. An empirical
      paper by Herde, Rossi, Pourtois, and Rauss (this issue) found that C1 was
      modulated by stimulus predictability, which indicates higher-level cognitive
      processes can modulate V1. A second discussion paper (Slotnick, this issue)
      compared experimental parameters across spatial attention studies and concluded
      certain stimulus, task, and analysis conditions were more likely to produce
      significant C1 attention effects. Commentaries were received by Fu (this issue),
      Qu and Ding (this issue), Zani and Proverbio (this issue), Pitts and Hillyard
      (this issue), Di Russo (this issue), and Mohr and Kelly (this issue). The author
      response included a more in depth analysis, and several studies that observed
      significant C1 attention effects survived critical analysis. The topics
      considered in this issue have clarified the current state of this debate and
      provided directions for future research.

PMID- 29065818
TI  - Antiresorptives: Safety Concerns-Clinical Perspective.
AB  - Antiresorptive drugs, such as amino-bisphosphonates and denosumab (Dmab), have
      dominated osteoporosis therapies for over 20 years. Since osteoporosis is a
      chronic disease, antifracture therapy could continue for the rest of a patient's
      life. Phase III clinical trials for antiresorptive drugs assessed relatively
      small patient populations for short durations and excluded up to 80% of patients
      who might seek osteoporosis therapy in clinical practice. Postmarketing reports
      based upon millions of patient-years and long-term (>5 years) clinical
      administration have associated some previously unknown, rare adverse events with
      antiresorptive use including osteonecrosis of the jaw (ONJ) and atypical femur
      fractures (AFFs). In the osteoporosis patient population, who receive much lower
      doses of bisphosphonate (BP) or Dmab, the incidence of ONJ is estimated at 0.001%
      to 0.01%, which is only slightly higher than that seen in the general population.
      AFFs are insufficiency or fissure transverse fractures originating on the lateral
      cortex of the subtrochanteric or diaphyseal region of the femur becoming oblique
      as they progress medially when complete. Incidence rates of AFF range from
      1.8/100,000 per year with a 2-year BP exposure to 113/100,000 per year with BP
      exposure from 8 to 9.9 years. Most recent pathogenic hypotheses of these rare
      events will be discussed.

PMID- 29065819
TI  - Feline Infectious Peritonitis: Immunohistochemical Features of Ocular
      Inflammation and the Distribution of Viral Antigens in Structures of the Eye.
AB  - Feline infectious peritonitis (FIP) is a serious, widely distributed systemic
      disease caused by feline coronavirus (FCoV), in which ocular disease is common.
      However, questions remain about the patterns of ocular inflammation and the
      distribution of viral antigen in the eyes of cats with FIP. This study
      characterized the ocular lesions of FIP including the expression of glial
      fibrillary acidic protein and proliferating cell nuclear antigen by Muller cells
      in the retina in cases of FIP and to what extent macrophages are involved in
      ocular inflammation in FIP. Immunohistochemistry for FCoV, CD3, CD79a, glial
      fibrillary acidic protein, calprotectin, and proliferating cell nuclear antigen
      was performed on paraffin sections from 15 naturally occurring cases of FIP and
      from controls. Glial fibrillary acidic protein expression was increased in the
      retina in cases of FIP. Muller cell proliferation was present within lesions of
      retinal detachment. Macrophages were present in FIP-associated ocular lesions,
      but they were the most numerous inflammatory cells only within granulomas (2/15
      cats, 13%). In cases of severe inflammation of the ciliary body with damage to
      blood vessel walls and ciliary epithelium (3/15, 20%), some macrophages expressed
      FCoV antigens, and immunolabeling for calprotectin on consecutive sections
      suggested that these FCoV-positive macrophages were likely to be recently derived
      from blood. In cases of severe and massive inflammation of most ocular structures
      (4/15, 26%), B cells and plasma cells predominated over T cells and macrophages.
      These results indicate that gliosis can be present in FIP-affected retinas and
      suggest that breakdown of the blood-ocular barrier can allow FCoV-bearing
      macrophages to access the eye.

PMID- 29065821
TI  - Modern Approach to Medical Diagnostics - the Use of Separation Techniques in
      Microorganisms Detection.
AB  - New analytical and molecular methods for microorganisms are being developed on
      various features of identification i.e. selectivity, specificity, sensitivity,
      rapidity and discrimination of the viable cell. The presented review was
      established following the current trends in improved pathogens separation and
      detection methods and their subsequent use in medical diagnosis. This
      contribution also focuses on the development of analytical and biological methods
      in the analysis of microorganisms, with special attention paid to bio-samples
      containing microbes (blood, urine, lymph, wastewater). First, the paper discusses
      microbes characterization, their structure, surface, properties, size and then it
      describes pivotal points in the bacteria, viruses and fungi separation procedure
      obtained by researchers in the last 30 years. According to the above, detection
      techniques can be classified into three categories, which were, in our opinion,
      examined and modified most intensively during this period: electrophoretic,
      nucleic-acid-based, and immunological methods. The review covers also the
      progress, limitations and challenges of these approaches and emphasizes the
      advantages of new separative techniques in selective fractionating of
      microorganisms.

PMID- 29065820
TI  - Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding
      Ability to its Anticancer Activity.
AB  - BACKGROUND: Considerable evidence demonstrates the importance of dithiocarbamates
      especially disulfiram as anticancer drugs. However there are no systematic
      reviews outlining how their metal-binding ability is related to their anticancer
      activity. This review aims to summarize chemical features and metal-binding
      activity of disulfiram and its metabolite DEDTC, and discuss different mechanisms
      of action of disulfiram and their contributions to the drug's anticancer
      activity. METHODS: We undertook a disulfiram-related search on bibliographic
      databases of peerreviewed research literature, including many historic papers and
      in vitro, in vivo, preclinical and clinical studies. The selected papers were
      carefully reviewed and summarized. RESULTS: More than five hundreds of papers
      were obtained in the initial search and one hundred eighteen (118) papers were
      included in the review, most of which deal with chemical and biological aspects
      of Disulfiram and the relationship of its chemical and biological properties.
      Eighty one (81) papers outline biological aspects of dithiocarbamates, and fifty
      seven (57) papers report biological activity of Disulfiram as an inhibitor of
      proteasomes or inhibitor of aldehyde dehydrogenase enzymes, interaction with
      other anticancer drugs, or mechanism of action related to reactive oxygen
      species. Other papers reviewed focus on chemical aspects of dithiocarbamates.
      CONCLUSION: This review confirms the importance of chemical features of compounds
      such as Disulfiram to their biological activities, and supports repurposing DSF
      as a potential anticancer agent.

PMID- 29065822
TI  - Privileged Structures in the design of Potential Drug Candidates for Neglected
      Diseases.
AB  - Privileged motifs are recurring in a wide range of biologically active compounds
      that reach different pharmaceutical targets and pathways and could represent a
      suitable start point to access potential candidates in the neglected diseases
      field. The current therapies to treat these diseases are based in drugs that lack
      of the desired effectiveness, affordable methods of synthesis and allow a way to
      emergence of resistant strains. Due the lack of financial return, only few
      pharmaceutical companies have been investing in research for new therapeutics for
      neglected diseases (ND). Based on the literature search from 2002 to 2016, we
      discuss how six privileged motifs, focusing phthalimide, isatin, indole,
      thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in
      compounds active against some of neglected diseases. It was observed that
      attention was paid particularly for Chagas disease, malaria, tuberculosis,
      schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African
      Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among
      the ND, antitrypanosomal and antiplasmodial activities were between the most
      searched. Besides, thiosemicarbazone moiety seems to be the most versatile and
      frequently explored scaffold. As well, phthalimide, isatin, thiazole, and
      thiazolidone nucleus have been also explored in the ND field. Some described
      compounds, appear to be promising drug candidates, while others could represent a
      valuable inspiration in the research for new lead compounds.

PMID- 29065823
TI  - Fluorescein-Inspired Near-Infrared Chemodosimeter for Luminescence Bioimaging.
AB  - Luminescence bioimaging is widely used for noninvasive monitoring biological
      targets in real-time with high temporal and spatial resolution. For efficient
      bioimaging in vivo, it is essential to develop smart organic dye platforms.
      Fluorescein (FL), a traditional dye, has been widely used in the biological and
      clinical study. However, the visible excitation and emission limited their
      further application for in vivo bioimaging. Near-infrared (NIR) dyes display
      prior advantageous of bioimaging because of their minimum absorption and photo
      damage to biological samples, as well as deep tissue penetration and low auto
      luminescence from background in living system. Thus, some great developments of
      near-infrared fluorescein-inspired dyes have been emerged for bioapplication in
      vitro and in vivo. In this review, we highlight the advances in the development
      of the near-infrared chemodosimeters for detecting and bioimaging based on the
      modification of fluorescein-inspired dyes naphtho-fluorescein (NPF) and cyanine
      fluorescein (Cy-FL).

PMID- 29065824
TI  - Statins and vulnerable plaque.
AB  - BACKGROUND: Atherosclerosis is a systemic, progressive lipid-driven inflammatory
      disease of the arterial vascular wall leading progressively to plaque
      development. The vulnerable plaque, the one considered to be the leading cause of
      cardiovascular events seems to exhibit a large and soft lipid-rich necrotic core
      covered by a thin and inflamed fibrous cap. Statin treatment is considered as one
      of the most effective methods for vulnerable plaque stabilization, currently
      being the principal drug in primary and secondary prevention of cardiovascular
      disease. OBJECTIVE: We sought to evaluate the beneficial effect of statins on
      biological processes involved in the evolution of vulnerable plaques Method: We
      performed a systematic review of the literature searching MEDLINE via Pubmed for
      all experimental and human studies implementing statins in vulnerable plaque.
      RESULTS: Statins seem to have a beneficial role in plaque stabilization and
      patient outcome. It seems that this effect is mediated by improving endothelial
      function, decreasing oxidative stress and inflammation, reducing inflammatory
      activation and inhibiting thrombogenic response. Although these data are quite
      promising, it remains to be determined the extent of a potent benefit of the
      pleiotropic effects of statin therapy in clinical setting. CONCLUSION:
      Prospective randomized trials should be conducted in order to further elucidate
      differences among type and dose of statin therapy, duration of treatment and
      association with LDL levels and clinical outcome.

PMID- 29065827
TI  - Effects of Arginine on Multimodal Chromatography: Experiments and Simulations.
AB  - Multimodal or mixed-mode chromatography can be used to separate various proteins,
      including antibodies. The separation quality and efficiency have been improved by
      the addition of solutes, especially arginine. This review summarizes the
      mechanism underlying the effects of arginine on protein elution in multimodal
      chromatography with neutral, anionic or cationic resin ligands; the mechanism has
      been investigated using experiments and molecular dynamics simulations. Arginine
      is effective in facilitating protein elution compared to salts and protein
      denaturants such as guanidine and urea. The unique elution effect of arginine can
      be explained by the interplay among arginine, proteins and the resin ligands.
      Arginine exhibits multiple binding modes for the ligands and further affinity for
      protein aromatic residues through its guanidinium group. These properties make
      arginine versatile for protein elution in multimodal chromatography. Taking into
      account that arginine is an aggregation suppressor for proteins but not a protein
      denaturant, arginine is a promising protein-eluting reagent for multimodal
      chromatography.

PMID- 29065825
TI  - 2-Hydroxypropyl-beta-cyclodextrins and the Blood-Brain Barrier: Considerations
      for Niemann-Pick Disease Type C1.
AB  - The rare, chronic, autosomal-recessive lysosomal storage disease Niemann-Pick
      disease type C1 (NPC1) is characterized by progressively debilitating and
      ultimately fatal neurological manifestations. There is an urgent need for disease
      modifying therapies that address NPC1 neurological pathophysiology, and passage
      through the blood-brain barrier represents an important consideration for novel
      NPC1 drugs. Animal investigations of 2-hydroxypropyl-beta-cyclodextrins
      (HPbetaCD) in NPC1 in mice demonstrated that HPbetaCD does not cross the blood
      brain barrier in significant amounts but suggested a potential for these complex
      oligosaccharides to moderately impact CNS manifestations when administered
      subcutaneously or intraperitoneally at very high doses; however, safety concerns
      regarding pulmonary toxicity were raised. Subsequent NPC1 investigations in cats
      demonstrated far greater HPbetaCD efficacy at much lower doses when the drug was
      administered directly to the CNS. Based on this, a phase 1/2a clinical trial was
      initiated with intrathecal administration of a specific, wellcharacterized
      mixture of HPbetaCD, with a tightly controlled molar substitution specification
      and a defined molecular "fingerprint" of the different species. The findings were
      very encouraging and a phase 2b/3 clinical trial has completed enrollment and is
      underway. In addition, phase 1 clinical studies utilizing high-dose intravenous
      administration of a different HPbetaCD are currently recruiting. Independent
      studies are needed for each product to satisfactorily address questions of
      safety, efficacy, dosing, and route of administration. The outcomes cannot be
      assumed to be translatable between HPbetaCD products and/or routes of
      administration.

PMID- 29065826
TI  - Green Synthesis of Palladium/Titanium Dioxide Nanoparticles and their Application
      for the Reduction of Methyl Orange, Congo Red and Rhodamine B in Aqueous Medium.
AB  - OBJECTIVE: Palladium nanoparticles (Pd NPs) supported on the TiO2 NPs were
      preparedusing Euphorbia thymifolia L. leaf extract. The Pd/TiO2 NPs were
      characterized by FESEM, EDS,TEM and XRD analysis and were used as nanocatalysts
      for the reduction of a variety of organicdyes. To the best of the author's
      knowledge, this study explains the first report to the synthesis ofPd/TiO2 NPs
      using Euphorbia thymifolia L. leaf extract. METHOD: 1.0 G of TiO2 was dispersed
      in 40 mL of 0.3 Mm PdCl2 solution and sonicated for 30 min.Then, 20 mL of the
      plant extract was mixed under continuous stirring at 60 degrees C for 2 h. The
      preparedPd/TiO2 NPs were centrifuged, washed and then dried. RESULTS: FESEM
      imaging showed the formation of NPs in the size range of 19-29 nm. The Pd/TiO2NPs
      exhibited high activity towards the reduction of Methyl Orange, Congo red and
      Rhodamine B inthe presence of NaBH4 in aqueous medium during 4, 1 and 54 s,
      respectively. CONCLUSION: The synthesis of the Pd/TiO2 NPs by this route is
      rapid, simple, less time consuming,environmentally safe and compatibility for
      medical and pharmaceutical applications because ofminimizing the use of toxic or
      hazardous organic solvents and reagents. Furthermore, thebiosyenthesized
      nanocatalyst can catalyze the reduction of organic dyes during short-time and can
      berecovered and recycled several times without significant loss of activity.

PMID- 29065828
TI  - Multimodal Chromatography for Purification of Biotherapeutics - A Review.
AB  - Process chromatography forms the core of purification of biotherapeutics. The
      unparalleled selectivity that it offers over other alternatives combined with the
      considerable robustness and scalability make it the unit operation of choice in
      downstream processing. It is typical to have three to five chromatography steps
      in a purification process for a biotherapeutic. Generally, these steps offer
      different modes of separation such as ion-exchange, reversed phase, size
      exclusion, and hydrophobic interaction. In the past decade, multimodal
      chromatography has emerged as an alternative to the traditional modes. It
      involves use of more than one mode of separation and typically combines ion
      exchange and hydrophobic interactions to achieve selectivity and sensitivity.
      Over the last decade, numerous authors have demonstrated the significant
      potential that multimode chromatography offers as a protein purification tool.
      This review aims to present key recent developments that have occurred on this
      topic together with a perspective on future applications of multimodal
      chromatography.

PMID- 29065830
TI  - Separation of Nucleic Acids Using Single- and Multimodal Chromatography.
AB  - The needs for purified nucleic acids for preparative and analytical applications
      have increased constantly, demanding for the development of new and more
      efficient methods for their recovery and isolation. DNA molecules harbour some
      intrinsic chemical properties that render them suitable for chromatographic
      separations. These include a negatively charged phosphate backbone as well as a
      hydrophobic character originating mainly from the major groove of DNA which
      exposes the base pairs on the surface of the molecule. In addition, single
      stranded DNA often allows for a free exposure of the hydrophobic aromatic bases.
      In this review, multimodal chromatography (MMC) has been evaluated as an
      alternative tool for complex separations of nucleic acids. MMC embraces more than
      one kind of interaction between the chromatographic ligand and the target
      molecules. These resins have often proved superior to conventional single-mode
      chromatographic materials for DNA isolation, including, e.g., the purification of
      plasmid DNA from crude cell lysates and for the preparation of DNA fragments
      before or after a polymerase chain reaction (PCR).

PMID- 29065829
TI  - Mixed Mode Chromatography: A Novel Way Toward New Selectivity.
AB  - Mixed mode chromatography offers a diversity of ligands, each providing a new
      selectivity. This allows the design of novel purification processes with reduced
      column steps. Structure of ligands is based on both hydrophobic and ionic groups.
      Thanks to its salt tolerance, crude extracts or post-IEX samples can be loaded
      directly without conditioning. The selectivity could be enhanced by modulating
      elution parameters or by using additives. More importantly, mixed mode
      chromatography could be as effective as affinity chromatography for mAb
      purification processes. Mixed mode chromatography opens the way to short and
      economical processes.

PMID- 29065831
TI  - Retention Mechanism of Proteins in Hydroxyapatite Chromatography - Multimodal
      Interaction Based Protein Separations: A Model Study.
AB  - BACKGROUND: Retention mechanism of proteins in hydroxyapatite chromatography
      (HAC) was investigated by linear gradient elution experiments (LGE). MATERIALS
      AND METHODS: Several mobile phase (buffer) solution strategies and solutes were
      evaluated in order to probe the relative contributions of two adsorption sites of
      hydroxyapatite (HA) particles, C-site due to Ca (metal affinity) and P-site due
      to PO4 (cation-exchange). When P-site was blocked, two basic proteins, lysozyme
      (Lys) and ribonuclease A(RNase), were not retained whereas cytochrome C(Cyt C)
      and lactoferrin (LF) were retained and also retention of acidic proteins became
      stronger as the repulsion due to P-site was eliminated. The number of the binding
      site B values determined from LGE also increased, which also showed reduction of
      repulsion forces. CONCLUSION: The selectivity (retention) of four basic proteins
      (RNase, Lys, Cyt C, LF) in HAC was different from that in ion-exchange
      chromatography. Moreover, it was possible to tune the selectivity by using NaCl
      gradient.

PMID- 29065832
TI  - Protein Solvent Interaction: Transition of Protein-solvent Interaction Concept
      from Basic Research into Solvent Manipulation of Chromatography.
AB  - Previously, we have reviewed in this journal (Arakawa, T., Kita, Y., Curr.
      Protein Pept. Sci., 15, 608-620, 2014) the interaction of arginine with proteins
      and various applications of this solvent additive in the area of protein
      formulations and downstream processes. In this special issue, we expand the
      concept of protein-solvent interaction into the analysis of the effects of
      solvent additives on various column chromatography, including mixed-mode
      chromatography. Earlier in our research, we have studied the interactions of such
      a variety of solvent additives as sugars, salts, amino acids, polymers and
      organic solvents with a variety of proteins, which resulted in mechanistic
      understanding on their protein stabilization and precipitation effects, the
      latter known as Hofmeister series. While such a study was then a pure academic
      research, rapid development of genetic engineering technologies and resultant
      biotechnologies made it a valuable knowledge in fully utilizing solvent additives
      in manipulation of protein solution, including column chromatography.

PMID- 29065833
TI  - On the Importance of Polyurethane and Polyurea Nanosystems for Future Drug
      Delivery.
AB  - BACKGROUND: During the last decade, polyurethanes and polyureas have emerged as
      promising alternatives to classical polyacrylate-, polyester- and polyaminoacid
      based drug delivery nanosystems. They are not only biocompatible and
      biodegradable, but also facilitate the manufacture of polymeric nanostructured
      nanoparticles in quantitative yields. The versatile chemistry reduces the amount
      of organic solvents used and allows the straightforward multifunctionalization of
      polymer precursors with the desired targeting molecule at each stage of the
      process. OBJECTIVES: To highlight the common issues encountered in current drug
      delivery systems (DDSs) and the state of the art of polyurethane and polyurea
      polymers that self-assemble in a stratified manner by hydrophobic interactions.
      Finally, we discuss the importance of taking a holistic view when applying
      polymer nanotechnologies, in order to enhance their efficiency during preclinical
      and clinical studies. CONCLUSIONS: Polyurethane-polyurea nanoparticles (PUUa NPs)
      emerge as suitable platforms to be manufactured in a cost-effective manner at
      industrial scale and following environmentally friendly synthetic methods.
      Furthermore, they allow the controlled delivery of a wide range of drugs and can
      be rapidly adapted to many clinical requirements by means of FDA-approved
      precursors. Additionally, the ease with which PUUa nanoparticles are biodegraded
      ensures control over temporal aspects of drug delivery compared to other
      nanosystems. These advantages make PUUa NPs attractive drug delivery vehicles as
      long as adequate safety and ethical guidelines for new NP formulations are
      developed.

PMID- 29065835
TI  - Hydroxypropyl-beta-Cyclodextrin Formulated in Nasal Chitosan Microspheres as
      Candidate Therapeutic Agent in Alzheimer's Disease.

PMID- 29065834
TI  - Polymeric Nano-Encapsulation of Curcumin Enhances its Anti-Cancer Activity in
      Breast (MDA-MB231) and Lung (A549) Cancer Cells Through Reduction in Expression
      of HIF-1alpha and Nuclear p65 (Rel A).
AB  - BACKGROUND: The anti-cancer potential of curcumin, a natural NFkappabeta
      inhibitor, has been reported extensively in breast, lung and other cancers. In
      vitro and in vivo studies indicate that the therapeutic efficacy of curcumin is
      enhanced when formulated in a nanoparticulate carrier. However, the mechanism of
      action of curcumin at the molecular level in the hypoxic tumour micro-environment
      is not fully understood. Hence, the aim of our study was to investigate the
      mechanism of action of curcumin formulated as nanoparticles in in vitro models of
      breast and lung cancer under an hypoxic microenvironment. METHODS: Biodegradable
      poly(lactic-co-glycolic acid) PLGA nanoparticles (NP), loaded with curcumin (cur
      PLGA-NP), were fabricated using a solvent evaporation technique to overcome
      solubility issues and to facilitate intracellular curcumin delivery. Cytotoxicity
      of free curcumin and cur-PLGA-NP was evaluated in MDA-MB-231 and A549 cell lines
      using migration, invasion and colony formation assays. All treatments were
      performed under an hypoxic micro-environment and whole cell lysates from controls
      and test groups were used to determine the expression of HIF-1alpha and p65
      levels using ELISA assays. RESULTS: A ten-fold increase in solubility, three-fold
      increase in anti-cancer activity and a significant reduction in the levels of
      cellular HIF-1alpha and nuclear p65 (Rel A) were observed for cur-PLGA-NP, when
      compared to free curcumin. CONCLUSION: Our findings indicate that curcumin can
      effectively lower the elevated levels of HIF-1alpha and nuclear p65 (Rel A) in
      breast and lung cancer cells under an hypoxic tumour micro-environment when
      delivered in nanoparticulate form. This applied means of colloidal delivery could
      explain the improved anti-cancer efficacy of curcumin and has further potential
      applications in enhancing the activity of anti-cancer agents of low solubility.

PMID- 29065836
TI  - Stability Indicating Liquid Chromatographic Method for Simultaneous Determination
      of Aspirin and Omeprazole.
AB  - BACKGROUND: Aspirin combination is prescribed for its thrombolytic activity where
      gastric ulceration is the major side effect of aspirin which can be prevented by
      combining it with proton pump inhibitor omeprazole. Present study describes
      development of analytical method for the estimation of aspirin and omeprazole in
      combination. OBJECTIVE: The aim of the present study was to develop and validate
      chromatographic method for simultaneous analysis of aspirin and omeprazole.
      METHODS: Isocratic, reversed phase stability indicating liquid chromatographic
      method was developed for the simultaneous determination of Aspirin and Omeprazole
      in combination. The separation was achieved on a Thermo Scientific Hypersil ODS
      (250 x 4.6 mm, 5 um) column, kept at ambient temperature, using acetonitrile:
      methanol: 0.05 M phosphate buffer (40:5:55; pH 4 adjusted with 0.1% tri ethyl
      amine) as a mobile phase at a flow rate of 1 mL/min and UV detection was
      performed at 225 nm. RESULTS: The retention time was found to be 3.9 min for
      aspirin and 5.3 min for omeprazole. The method was observed to be linear in the
      range of 2 - 80 ug/mL for aspirin and 1 - 40 ug/mL for omeprazole, respectively.
      The proposed method was validated as per ICH guidelines Q2 (R1). The developed RP
      HPLC method was successfully applied for the simultaneous estimation of aspirin
      and omeprazole in the presence of degradation products of both the drugs.
      CONCLUSION: The present study describes liquid chromatographic method for the
      estimation of aspirin and omeprzole in combination. The method can be used for
      the analysis of stability samples and routine quality control samples.

PMID- 29065837
TI  - USP7: Target Validation and Drug Discovery for Cancer Therapy.
AB  - BACKGROUND: USP7 (ubiquitin specific protease 7, also known as HAUSP) is one of
      the deubiquitinating enzymes (DUB) that reverses ubiquitination and spares
      substrate proteins from degradation. METHODS: After a brief introduction of
      ubiquitin-proteasome system (UPS) and human DUB, this review focuses on the
      structural and functional complexity of USP7 in tumor development and
      progression. Afterwards, physiological regulatory mechanisms and manipulation
      strategies for USP7 are elaborated. Finally, we discuss the advances and
      difficulties of USP7 as a novel therapeutic target for cancer. RESULTS: It is
      mostly concerned that USP7 regulates the dynamics of the p53 and Mdm2 network by
      deubiquitinating both p53 and its E3 ubiquitin ligase, Mdm2. Recently, USP7 has
      also been recognized as a regulator of many other tumor associated proteins such
      as FOXO, PTEN and Claspin, consequently being involved in cell cycle control, DNA
      damage response, apoptosis and many other cellular processes. Consistently,
      aberrant USP7 expression and activity have been connected to various types of
      cancers, which along with lots of validating genetic and functional experiments
      make this enzyme a compelling target for the treatment of cancer. Currently
      disclosed inhibitor discovery programs and relevant research have identified
      several synthetic small molecules, natural compounds, small peptides and one
      ubiquitin variant that have specific USP7 inhibitory effects and considerable
      antitumor activities. CONCLUSION: Taken together, USP7 is a promising therapeutic
      target and USP7 inhibitors hold promise as a new approach to cancer therapy.

PMID- 29065838
TI  - Synthesis, Structure and Antiproliferative Activity of New pyrazolo[4,3-
      e]triazolo[4,5-b][1,2,4]triazine Derivatives.
AB  - BACKGROUND: Triazoles and their fused derivatives are an important class of
      compounds that exhibit interesting biological properties, such as antiasthmatic,
      antimicrobial, antifungal, analgesic, antiallergic, antiinflammatory, herbicidal,
      plant growth regulative activity, and anti-HIV-1 activities. Moreover, anticancer
      activity of 1,2,4-triazole containing derivatives has been documented. Due to the
      fact a convenient approach toward polycyclic frameworks containing fused 1,2,4
      triazoles was described. OBJECTIVE: The objective of this article is the
      synthesis of new pyrazolo[4,3-e]triazolo[4,5- b][1,2,4]triazine derivatives with
      potential antiproliferative activity. METHODS: Cancer cell proliferation was
      analysed by means of MTT assay after 96 h treatment. IC50 was calculated using
      computerized linear regression analysis of quantal log doseprobit functions,
      according to the method of Litchfield and Wilcoxon. X-ray data were collected on
      the Bruker SMART APEX II CCD diffractometer; The structure was solved by direct
      methods using SHELXS-2013 and refined by full-matrix least-squares with SHELXL
      2014/7. All calculations were performed using WINGX version 2014.1 package.
      RESULTS: The series of pyrazolo[4,3-e]triazolo[4,5-b][1,2,4]triazine derivatives
      were synthesized. MTT assay revealed that the compounds inhibited cancer cells
      growth at concentrations below 10 uM. The tested compounds showed higher
      antiproliferative activity than popular cytostatics cisplatin (lung carcinoma)
      and 5-fluorouracil (colon adenocarcinoma). X-ray examinations showed that final
      products in the crystalline phase have a linear form. CONCLUSION: In the paper we
      have reported the synthesis and spectroscopic analysis of new condensed tricyclic
      derivatives of the pyrazolo[4,3-e]triazolo[4,5-b][1,2,4]triazine. MTT analysis
      revealed concentration-dependent decrease in lung A549 and colon LS180 cancer
      cells proliferation. In order to explain the molecular mechanisms involved in
      anticancer activity of pyrazolo[4,3- e]triazolo[4,5-b][1,2,4]triazine
      derivatives, our research will be continued.

PMID- 29065839
TI  - Anthranilic Acid Derivatives: Novel Inhibitors of Protein Glycation and the
      Associated Oxidative Stress in the Hepatocytes.
AB  - BACKGROUND: Anthranilic acid derivatives are important pharmacophores in drug
      discovery. Several of them are currently being used, such as mefenamic acid and
      meclofenamates, possess analgesic, anti-inflammatory and antipyretic activities.
      Some anthranilic acid-based scaffolds have also been reported for the management
      of metabolic disorders. OBJECTIVES: The aim of the current study was to
      investigate the antiglycation potential of 2-anilino benzoic acid derivatives
      against (N-phenylanthranilic acid) fructose- human serum albumin (HSA) glycation.
      The study also analyzed the effects of newly identified antiglycation inhibitors
      on AGEs-mediated intracellular reactive oxygen species production, and associated
      impaired proliferation of the hepatocytes. METHODS: The present study focuses on
      the antiglycation activity of 2- anilinobenzoic acid derivatives 1-18 in in-vitro
      human serum albumin (HSA)- fructose model. These derivatives were also identified
      as non-toxic to 3T3 mouse fibroblast cell-line using metabolic assay. The effect
      of the most promising derivative 1, 2- (2, 4- dinitroanilino)benzoic acid, was
      studied in a dose dependent manner, co-incubated with fructose-derived AGEs (0-
      200 MUg/mL), on rat hepatocytes proliferation and associated intracellular
      generation of ROS via MTT assay and DCFH-DA technique, respectively. RESULTS: We
      found that derivative 1 ameliorates the elevated intracellular oxidative stress
      and associated diminished proliferation of the hepatocytes in response to AGEs.
      CONCLUSION: In conclusion, we identify novel 2- anilino benzoic acid derivatives
      as antiglycation agents through in-vitro and cellular-based models.

PMID- 29065840
TI  - Design, Synthesis, and Evaluation of (2-(Pyridinyl)methylene)-1-tetralone
      Chalcones for Anticancer and Antimicrobial Activity.
AB  - BACKGROUND: Chalcones, natural products produced by plants as a natural defense
      mechanisms against various pathogens, are molecules with structures that include
      two aromatic rings joined by an alpha, beta unsaturated carbonyl system. Previous
      research has demonstrated that chalcones exhibit a wide variety of biological
      activities, including anticancer, antifungal, and antibiotic properties.
      OBJECTIVE: Our goal is to synthesize novel heterocyclic-containing chalcones and
      have their biological activities evaluated. Methods Sixteen chalcones were
      synthesized by the crossed aldol condensation of substituted tetralones with
      substituted pyridinylaldehydes. The products were purified by recrystallization
      in MeOH/H2O and characterized by 1H NMR, 13C NMR, and HRMS. Anticancer assays
      were performed by NCI (National Cancer Institute) against the NCI-60 panel of 60
      different human cancer cell lines, including leukemia, non-small-cell lung
      cancer, colon, central nervous system, melanoma, ovarian, renal, prostate, and
      breast cancer. Antimicrobial assays were performed by COADD (Community for Open
      Antimicrobial Drug Discovery) against Escherichia coli, Klebsiella pneumonia,
      Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus,
      Cryptococcus neoformans var. grubii, and Candida albicans. RESULT: Chalcone 3d
      had demonstrated growth inhibition greater than 60% against a variety of cancers:
      leukemia (MOLT-4, SR), non-small cell lung cancer (NCI-H522), colon cancer (HCT-
      116), prostate cancer (DU-145), and breast cancer (MCF7, MDA-MB-468) and was also
      cytotoxic to three different cell lines (CCRF-CEM, RPMI-8226, and KM12). 5c was
      active against leukemia (CCRF-CEM, RPMI-8226, SR) and breast cancer (MCF7) and 5e
      was active only against leukemia (RPMI-8226, SR). 5h was partially active and the
      best compound with growth inhibition of MRSA by 75%. 3b was the best compound
      against EC, KP, and PA and 3f had the greatest activity against AB. For fungi, 3f
      and 3e demonstrated the best growth inhibition. CONCLUSION: A small library of
      heterocyclic-containing chalcones was developed and initial screening
      demonstrates modest activity against cancers, bacteria, and fungi.

PMID- 29065841
TI  - Synthesis, Cytotoxicity Evaluation, Molecular Docking and Utility of Novel
      Chalcones as Precursors for Heterocycles Incorporating Pyrazole Moiety.
AB  - BACKGROUND: Chalcones, 2-pyrazolines and thiazoles have been reported to possess
      various pharmacological activities. OBJECTIVE: Synthesis of new chalcones and
      utilizing them as a building block for constructing a series of thiazole
      derivatives and evaluating some of them as anticancer agents. METHOD: The new
      compounds were synthesized via stirring at room temperature or thermal heating.
      Cytotoxic evaluation of the new synthesized compounds was tested using the method
      of Skehan et al. Moreover, the computational studies were performed using MOE
      2014.09 software. RESULT: A series of new chalcones were prepared by the reaction
      of ethyl 3-acetyl-1-aryl-5-methyl- 1H-pyrazole-4-carboxylate with a number of
      substituted benzaldehydes. One of these chalcones was used as a building block
      for constructing a pyrazoline ring via its reaction with thiosemicarbazide. The
      produced carbothioamide derivative was used for the preparation of two series of
      thiazole derivatives by its reaction with a number of hydrazonoyl chlorides.
      Moreover, reaction of 3- acetylpyrazole thiosemicarbazone derivative with a
      number of N-aryl-2-oxopropane hydrazonoyl chlorides afforded 5-arylazothiazole
      derivatives. The assigned structures for all the newly synthesized compounds were
      confirmed on the basis of elemental analyses and spectral data. Some of the newly
      synthesized chalcones and thiazoles were tested for their cytotoxicity against
      human colon carcinoma cell line (HCT-116) and the molecular docking was carried
      out on the most active compound 3f. CONCLUSION: The results of the anticancer
      activity revealed that compounds 3f, 3e, 3c and 3b have promising activities
      compared with the standard drug Doxorubicin. Moreover, the computational studies
      confirm the results of biological activity. Also, the ADME profile study showed
      that compound 3f can be considered as a promising drug by conducting good
      pharmacokinetic and medicinal chemistry tests.

PMID- 29065842
TI  - Effects of Vaccination Against the H1N1 Virus on BDNF and TNF-alpha Plasma Levels
      in Pregnant Women.
AB  - BACKGROUND: Vaccination is a widespread strategy to protect women and their
      children during fetal development. However, there is a lack of knowledge about
      potential effects of H1N1 vaccination on concentration of cytokines that are
      important to mother's central nervous system functions and fetal
      neurodevelopment. OBJECTIVE: The main purpose of the present study was to
      evaluate such interaction. The specific goals were to study the effects of
      vaccination against the H1N1 virus on plasma levels of the Brain Derived
      Neurotrophic Factor(BDNF), Tumor Necrosis Factor-alpha (TNF-alpha) and TNF-alpha
      Receptors 1 and 2 (sTNFR1; sTNFR2), in different periods of gestation. METHODS:
      Data were obtained during the period of 6 months in 2010, from a sample of 94
      pregnant women who were using the health care service of Conceicao do Mato
      Dentro, a rural area in the state of Minas Gerais, Brazil. Seventeen women were
      in the first trimester of pregnancy, forty were in the second trimester and 37
      were in the third trimester. Each of these groups was divided into two subgroups
      as follows: immunized against the H1N1 virus (I) and non-immunized (NI). Plasma
      concentrations of BDNF, TNF-alpha, sTNFR1 and sTNFR2 were measured using the
      sandwich ELISA. RESULTS: There was no difference in cytokine or neurotrophic
      factor levels evaluated between groups I and NI in any trimesters. CONCLUSION:
      These results show that the recommendation of vaccination against the H1N1 virus
      for all pregnant women as a public health measure could be considered safe,
      regarding aspects related to the role played by neurotrophin and cytokine, such
      as those of CNS development and immunological functions.

PMID- 29065843
TI  - Dual Antibacterial and Anticancer Activity of 4-Benzoyl-1
      dichlorobenzoylthiosemicarbazide Derivatives.
AB  - OBJECTIVE/METHOD: A group of 4-benzoyl-1-dichlorobenzoylthiosemicarbazides
      endowed with antibacterial activity was evaluated for its cytotoxic properties
      against breast cancer cells (MCF-7, MDA-MB-231) and head and neck squamous cell
      carcinomas (FaDu, SCC-25). Cytotoxicity of the investigated compounds was
      measured using MTT and [3H]-thymidine incorporation bioassays. RESULT: 1-(2,3
      Dichlorobenzoyl)-4-(2-methylbenzoyl)thiosemicarbazide (TA-4), 1-(2,4
      dichlorobenzoyl)- 4-(2-methylbenzoyl)thiosemicarbazide (TA-18), and 1-(2,4
      dichlorobenzoyl)-4-(4-nitrolbenzoyl)- thiosemicarbazide (TA-20) were found to
      possess anticancer activity equipotent or even stronger than that of reference
      drug - etoposide. In order to clarify the molecular mode of action of the
      mentioned compounds, the relaxation assay kit for human DNA topoisomerase II was
      used. It turned out that reduction of viability of cancer cells was a result of
      inhibition of human DNA topoII. Molecular docking studies proved that 4-benzoyl-1
      dichlorobenzoylthiosemicarbazides strongly interact with DNAdependent subunit of
      that enzyme.

PMID- 29065844
TI  - Oleanolic Acid Inhibits Colorectal Cancer Angiogenesis by Blocking the VEGFR2
      Signaling Pathway.
AB  - BACKGROUND: Angiogenesis is a crucial process that regulated by multiple
      intracellular signaling pathways including MEK/ERK and JNK/SAPK. Thus, many
      inhibitors have developed to these pathways as anti-cancer therapeutic
      strategies. Oleanolic acid (OA) is a natural pentacyclic triterpenoic acid
      compound that present in various herbal medicines. It has been used as antitumor
      agent for various cancers including colorectal cancer (CRC), which attenuates
      angiogenesis. OBJECTIVE: To study the molecular mechanism of OA suppressing
      angiogenesis. METHOD: The proliferation of human umbilical vein endothelial cells
      (HUVECs) was determined by MTT and the invasion and migration of them were
      measured by wound-healing Assay, transwell migration assay and tube formation
      assay. The xenograft mouse model was used to study the effect of OA blocking
      angiogenesis in vivo. The Western blot was used to checked the phosphorylation of
      VEGFR2. RESULTS: OA attenuates HUVECs invasion, migration, tube formation and
      vascular sprouting. Moreover, OA suppresses HUVECs sprout and tube formation.
      Importantly, OA also blocks angiogenesis in HUVECs and colorectal cancer cells
      (HCT-116) both in vitro and in vivo. OA-dependent suppression of tumor
      angiogenesis mediated by blocking the phosphorylation of the vascular endothelial
      growth factor receptor-2 (VEGFR2) that results in inhibition of MEK/ERK/JNK
      pathway. CONCLUSION: Our results suggest that inhibition of tumor angiogenesis
      via the suppression VEGFR2 phosphorylation may be one of the underlying
      mechanisms by which OA exerts its anti-cancer effect.

PMID- 29065845
TI  - Identification of Electrophysiological Changes in Alzheimer's Disease: A
      Microarray Based Transcriptomics and Molecular Pathway Analysis Study.
AB  - BACKGROUND & OBJECTIVE: Involvement of amyloid beta and tau proteins in
      pathogenesis of Alzheimer's disease (AD) has been studied extensively. However,
      electrophysiological activity, and cellular processes like membrane transport are
      mostly unstudied. Electrophysiological processes provide a bridge between brain
      activity and cognition, and show promise as translatable biomarkers in
      preclinical and clinical applications. Biochemical imbalance leads to change in
      glutamate-based neurotransmission, antioxidant capacity, and in membrane
      polarization-repolarization events, eventually, resulting in AD. We hypothesize
      that in AD, these processes are unified at a single metabolic hub and we carried
      out a holistic system-biology approach. METHOD: In the present study, we
      integrated and analyzed multiple AD expression datasets from the GEO database to
      identify significant genes associated with electrophysiological pathways and
      attempted determination of interconnected canonical molecular pathways. Partek
      Genomic suite based expression analysis identified 200 significantly expressed
      genes using cut-off value of <= 0.05 and 2 fold change. Transducer of ERBB2, 2
      (TOB2); lactotransferrin (LFT) and RAS-like, family 12 (RASL12) were most up
      regulated genes, while neurofilament light polypeptide (NEFL); collagen, type V,
      alpha 2 (COL5A2); visinin-like 1 (VSNL1); cannabinoid receptor 1 (brain) (CNR1);
      neurofilament, medium polypeptide (NEFM); regulator of G-protein signaling 4
      (RGS4), and synaptosomalassociated protein, 25kDa (SNAP25) were most down
      regulated ones. CONCLUSION: Interestingly, we found majority of transporter genes
      identified in dataset as downregulated. Ingenuity pathways analysis revealed
      glutamate receptor signaling, CREB signaling, dopamine- DARPP32 feedback in cAMP
      signaling, fMLP signaling in neutrophils, and synaptic long term potentiation
      pathway playing critical role in AD pathophysiology and having correlation with
      electrophysiological dysfunction.

PMID- 29065846
TI  - Computational Determination of the Effects of Bacteriophage Bacteriophage
      Interactions in Human Body.
AB  - BACKGROUND: Chronic diseases are becoming more serious and widely spreading and
      this carries a heavy burden on doctors to deal with such patients. Although many
      of these diseases can be treated by bacteriophages, the situation is
      significantly dangerous in patients having concomitant more than one chronic
      disease, where conflicts between phages used in treating these diseases are very
      closer to happen. METHOD: This research paper presents a method to detecting the
      Bacteriophage-Bacteriophage Interaction. This method is implemented based on
      Domain-Domain Interactions model and it was used to infer Domain-Domain
      Interactions between the bacteriophages injected in the human body at the same
      time. RESULTS: By testing the method over bacteriophages that are used to treat
      tuberculosis, salmonella and virulent E.coli, many interactions have been
      inferred and detected between these bacteriophages. Several effects were detected
      for the resulted interactions such as: playing a role in DNA repair such as
      nonhomologous end joining, playing a role in DNA replication, playing a role in
      the interaction between the immune system and the tumor cells and playing a role
      in the stiff man syndrome. We revised all patents relating to bacteriophage
      bacteriophage interactions and phage therapy. CONCLUSION: The proposed method is
      developed to help doctors to realize the effect of simultaneously injecting
      different bacteriophages into the human body to treat different diseases.

PMID- 29065847
TI  - Long-term Administration of Antipsychotic Drugs in Schizophrenia and Influence of
      Substance and Drug Abuse on the Disease Outcome.
AB  - BACKGROUND: Many schizophrenic patients with a long-term administration of
      antipsychotic drugs do not regularly adhere to the prescribed pharmacotherapy.
      Antipsychotic drugs constitute a palliative, but not a curative treatment, and
      the long-term effect of these drugs is not secure. Patients tend to consume
      nicotine and alcohol, as well as some patients consume drugs such as cannabis and
      amphetamines. OBJECTIVE: The objective of this mini-review is to examine the
      reasons for the high tendency of schizophrenic patients to consume alcohol,
      nicotine and drugs and in addition to suggest measures to reduce the abuse of
      substances and drugs. The effects of substances such as alcohol and nicotine and
      drugs such as cannabis and amphetamines on the disease outcome will be mentioned.
      METHOD: Previous reviews on the psychotic disorders and the pharmacological
      treatment were used to examine the effects of substances and drugs on
      schizophrenic symptoms and to investigate appropriate measures to improve
      medication adherence and the renouncement of consuming substances and drugs.
      RESULTS: A possible coherence between the function of single susceptibility genes
      and the alteration of neurotransmitters is mentioned. The mechanism of action of
      the most important secondgeneration antipsychotic drugs and their indications are
      described. The tendency of schizophrenic patients to consume alcohol and nicotine
      and in addition the effect of both substances to possibly worsen psychotic
      symptoms are pointed out. The effect of nicotinergic agonists to support smoking
      cessation is described. The different compounds of cannabis,
      tetrahydrocannabidiol (a psychotomimetic) and cannabidiol (exerts antipsychotic
      actions), are mentioned. Because a reduced adherence to the pharmacotherapy is
      frequently combined with the abuse of substances, additional drugs,
      psychoeducation and the administration of long-acting injectable antipsychotic
      drugs could reduce the abuse of substances and drugs; these strategies could help
      to maintain the antipsychotic administration. CONCLUSION: The abuse of drugs and
      substances might be combined with a reduced adherence to the antipsychotic
      pharmacotherapy. Drugs and substances might in some cases worsen the psychotic
      symptoms. Appropriate measures to reduce substance and drug abuse as well as to
      improve the adherence to the antipsychotic pharmacotherapy are cognitive
      behavioral therapy, psychoeducation and the administration of long-acting
      injectable antipsychotic drugs. Some new drugs, for example the cannabis compound
      cannabidiol that shows antipsychotic properties and beta-varenicline, a
      nicotinergic cholinergic agonist, might be administered when substance abuse
      (cannabis, nicotine) occurs.

PMID- 29065848
TI  - Cytotoxicity of Nanomaterials: Using Nanotoxicology to Address the Safety
      Concerns of Nanoparticles.
AB  - BACKGROUND: The rapid progress in the application of different types of
      nanoparticles in various biomedical applications resulted in substantial increase
      in the use of these materials. The special physicochemical properties like small
      size and increased surface area offered by nanoparticles may pose unexpected
      toxicologic threats despite of offering promising biological effects. OBJECTIVE:
      The intended as well as unintended exposure of nanoparticles to humans is a major
      challenge for the expanding field of nanoparticle therapy. In this review, an
      attempt has been made to briefly discuss the different factors affecting
      nanoparticle mediated toxicity, mechanism of toxicity, and interference of NPs
      with bioassays. A comprehensive overview has been provided for the in vitro and
      in vivo toxicologic assessment of NPs and what and how framing guidelines should
      be used for global unification of nanotoxicologic studies. CONCLUSION: The
      present review entails a discussion of the toxicity of nanoparticles along with
      interferences inherent to nanoparticles in toxicity studies. The lack of
      availability of regulatory guidelines for nanoparticles is one of the biggest
      issues. Our understanding of the mechanisms of NP-induced toxicity is
      superficial; thus, it is too early to come to a general consensus on the toxicity
      of NPs. There is a need, therefore, to standardize and validate the toxicity
      testing assays based on NPs properties.

PMID- 29065849
TI  - Biocompatible Synthetic and Semi-synthetic Polymers - A Patent Analysis.
AB  - BACKGROUND: Bioengineering has come of ages by setting up spare parts
      manufacturing units to be used in human body such as invasive implants and
      interventional controlled drug delivery in vivo systems. As a matter of fact
      patients on basis of their fiscal strength have the option to undergo
      prophylactic tactical manoeuvre for longer life spans. In this sphere of invasive
      implants, biocompatible polymer implants are a state of the art cutting edge
      technology with outstanding innovations leading to number of very successful
      start-up companies with a plethora of patent portfolios. OBJECTIVE: From 2000
      onwards, patent filings and grants for biocompatible polymers are expanding.
      Currently definition of biocompatibility is quite ambiguous with respect to the
      use of FDA approved polymeric materials. This article analysed patent portfolios
      for the trend patterns of prolific biocompatible polymers for capitalization and
      commercialization in the forthcoming years. METHODS: Pair Bulk Data (PBD) portal
      was used to mine patent portfolios. In this patent preliminary analysis report,
      patents from 2000 to 2015 were evaluated using 317(c) filings, grants and
      classifications data for poly(vinyl alcohol) (PVA), poly(glycolic acid) (PGA),
      poly(hydroxyalkanoates) (PHAs) and poly(lactic acid) (PLA). CONCLUSION: This
      patent portfolio preliminary analysis embarks into patent analysis for New
      Product Development (NPD) for corporate R&D investment managerial decisions and
      on government advocacy for federal funding which is decisive for developmental
      advances. An in-depth patent portfolio investigation with return of investment
      (RoI) is in the pipeline.

PMID- 29065850
TI  - Evaluation of Antioxidant Capacity and Phenolic Content in Ethanolic Extracts of
      Leaves and Flowers of Some Asteraceae Species.
AB  - BACKGROUND: Medicinal plants contain large amount of natural antioxidant
      compounds, which enable them to neutralize free radicals. Asteraceae family is an
      important source of phytochemical compounds. OBJECTIVE: The objective of this
      research is to find out the antioxidant potential and radical scavenging from the
      leaf and flowers of five species (Artemisia absinthium L., Arctium lappa L.,
      Silybum marianum L., Centaurea cyanus L. and Echinops ritro L.) of the Asteraceae
      family. This research includes recent patents (US20110179530A1) in plant
      biotechnology. METHODS: The plant extract obtained by absolute extraction method
      was investigated for Total Phenolic Content (TPC), total Flavonoid Content (TFC),
      Total Antioxidant Capacity (TAC), and Chain Breaking Activity (CBA).
      THIOBARBIOTURIC ACID (TBA), 2,2-diphenyl-1-picrylhydrazyl (DPPH), IC50, nitric
      oxide (NO), hydrogen peroxide (H2O2), superoxide (O-) radical scavenging and
      Ferric Reducing Antioxidant Power (FRAP) were also measured. RESULTS: The results
      showed the highest values for the TPC, TBA, FRAP and DPPH radical scavenging
      related to A. absinthium. While, A. lappa extract showed the maximum content for
      TFC, TAC, CBA and O2 radical scavenging. In addition, our results indicated that
      E. ritro is a good source of NO2 and H2O2 radical scavenging activity (P<0.05).
      Our findings suggest that the flower is more successful than the leaf.
      CONCLUSION: Artemisia absinthium, A. lappa and E. ritro can be used as an easily
      accessible source of natural antioxidants and as a possible food supplement or in
      pharmaceutical industry.

PMID- 29065851
TI  - The protective effect of activating Nrf2 / HO-1 signaling pathway on
      cardiomyocyte apoptosis after coronary microembolization in rats.
AB  - BACKGROUND: Myocardial apoptosis is closely related to myocardial injury caused
      by coronary microembolization (CME).Nuclear factor erythroid 2-like (Nrf2) has
      been taken into account as an inhibitor of apoptosis in various tissues. Thus,
      this research aims to investigate which part Nrf2/HO-1 signaling pathway plays in
      myocardial apoptosis process following the effect of CME on rats. METHODS:
      Separate 40 rats then form them into a group of shame, a group of CME, a group of
      CME plus AAV-Nrf2(AAV-Nrf2 (CME) group) and a group of CME plus AAV-control (AAV
      control (CME) group) stochastically and averagely. Rat CME was established by
      injecting into the left ventricular chamber, with or without pretreatment of
      adeno-associated virus Nrf2 (AAV-Nrf2). Echocardiological measurements, using
      Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) to
      stain, conducting Quantitative PCR in real time (RT-PCR) as well as Western
      blotting to evaluate the impacts of them functionally, morphologically and
      molecularly in CME. RESULTS: Nrf2 decreased in cardiomyocytes after CME.
      Upregulation of Nrf2 inside an organism through AAV connect to improving the
      function of heart as well as attenuating myocardial apoptosis, following the
      restrain of proapoptotic mRNAs and proteins like caspase-3, caspase-9 and bax
      expressing as well as the increase of antiapoptotic mRNA and proteins like HO-1
      and bcl-2 expressing. CONCLUSION: Activation of Nrf2/HO-1 pathway can improve CME
      induced cardiac dysfunction effectively and also reduce the myocardial apoptosis.

PMID- 29065852
TI  - Genetic determinants of growth hormone and GH-related phenotypes.
AB  - BACKGROUND: Higher fasting Growth Hormone (GH) has been associated with increased
      cardiovascular morbidity and mortality. Our objective was to find genetic
      determinants of fasting GH in order to facilitate future efforts of analyzing the
      association between fasting growth hormone and cardiovascular disease. A genome
      wide association study (GWAS) was performed in a discovery cohort of 4134 persons
      (58% females; age 46-68 yrs), linking SNPs to fasting hs-GH. Fifteen SNPs were
      replicated in an independent cohort of 5262 persons (28.9% females; age 56-85
      yrs). The best performing SNP was analyzed vs GH-related variables in a third
      independent cohort (n = 24,047; 61% females; age 44-73 yrs). A candidate gene
      approach searched for significant SNPs in the genes GH1 and GHR in the discovery
      cohort and was replicated as previously described. RESULTS: In the GWAS, the
      minor allele of rs7208736 was associated with lower GH in the discovery cohort (p
      = 5.15*10^-6) and the replication cohort (p = 0.005). The GH reducing allele was
      associated with lower BMI (P = 0.026) and waist (P = 0.021) in males only. In the
      candidate gene approach rs13153388 in the GHR-gene was associated with elevated
      GH-levels (P = 0.003) in the discovery cohort only and reduced height (P =
      0.003). CONCLUSION: In the first GWAS ever for GH, we identify a novel locus on
      chromosome 17 associated with fasting GH levels, suggesting novel biological
      mechanisms behind GH secretion and GH-related traits. The candidate gene approach
      identified a genetic variant in the GHR, which was associated with an elevation
      of fasting hs-GH and lower height suggesting reduced GHR ligand sensitivity. Our
      findings need further replication.

PMID- 29065854
TI  - Correction to: Development and validation of a risk score to assist screening for
      acute HIV-1 infection among men who have sex with men.

PMID- 29065853
TI  - An optimized approach for annotation of large eukaryotic genomic sequences using
      genetic algorithm.
AB  - BACKGROUND: Detection of important functional and/or structural elements and
      identification of their positions in a large eukaryotic genomic sequence are an
      active research area. Gene is an important functional and structural unit of DNA.
      The computation of gene prediction is, therefore, very essential for detailed
      genome annotation. RESULTS: In this paper, we propose a new gene prediction
      technique based on Genetic Algorithm (GA) to determine the optimal positions of
      exons of a gene in a chromosome or genome. The correct identification of the
      coding and non-coding regions is difficult and computationally demanding. The
      proposed genetic-based method, named Gene Prediction with Genetic Algorithm
      (GPGA), reduces this problem by searching only one exon at a time instead of all
      exons along with its introns. This representation carries a significant advantage
      in that it breaks the entire gene-finding problem into a number of smaller sub
      problems, thereby reducing the computational complexity. We tested the
      performance of the GPGA with existing benchmark datasets and compared the results
      with well-known and relevant techniques. The comparison shows the better or
      comparable performance of the proposed method. We also used GPGA for annotating
      the human chromosome 21 (HS21) using cross-species comparisons with the mouse
      orthologs. CONCLUSION: It was noted that the GPGA predicted true genes with
      better accuracy than other well-known approaches.

PMID- 29065855
TI  - Spatio-temporal pattern analysis for evaluation of the spread of human infections
      with avian influenza A(H7N9) virus in China, 2013-2014.
AB  - BACKGROUND: A large number (n = 460) of A(H7N9) human infections have been
      reported in China from March 2013 through December 2014, and H7N9 outbreaks in
      humans became an emerging issue for China health, which have caused numerous
      disease outbreaks in domestic poultry and wild bird populations, and threatened
      human health severely. The aims of this study were to investigate the directional
      trend of the epidemic and to identify the significant presence of spatial
      temporal clustering of influenza A(H7N9) human cases between March 2013 and
      December 2014. METHODS: Three distinct epidemic phases of A(H7N9) human
      infections were identified in this study. In each phase, standard deviational
      ellipse analysis was conducted to examine the directional trend of disease
      spreading, and retrospective space-time permutation scan statistic was then used
      to identify the spatio-temporal cluster patterns of H7N9 outbreaks in humans.
      RESULTS: The ever-changing location and the increasing size of the three
      identified standard deviational ellipses showed that the epidemic moved from east
      to southeast coast, and hence to some central regions, with a future
      epidemiological trend of continue dispersing to more central regions of China,
      and a few new human cases might also appear in parts of the western China.
      Furthermore, A(H7N9) human infections were clustering in space and time in the
      first two phases with five significant spatio-temporal clusters (p < 0.05), but
      there was no significant cluster identified in phase III. CONCLUSIONS: There was
      a new epidemiologic pattern that the decrease in significant spatio-temporal
      cluster of A(H7N9) human infections was accompanied with an obvious spatial
      expansion of the outbreaks during the study period, and identification of the
      spatio-temporal patterns of the epidemic can provide valuable insights for better
      understanding the spreading dynamics of the disease in China.

PMID- 29065857
TI  - CGDV: a webtool for circular visualization of genomics and transcriptomics data.
AB  - BACKGROUND: Interpretation of large-scale data is very challenging and currently
      there is scarcity of web tools which support automated visualization of a variety
      of high throughput genomics and transcriptomics data and for a wide variety of
      model organisms along with user defined karyotypes. Circular plot provides
      holistic visualization of high throughput large scale data but it is very complex
      and challenging to generate as most of the available tools need informatics
      expertise to install and run them. RESULT: We have developed CGDV (Circos for
      Genomics and Transcriptomics Data Visualization), a webtool based on Circos, for
      seamless and automated visualization of a variety of large scale genomics and
      transcriptomics data. CGDV takes output of analyzed genomics or transcriptomics
      data of different formats, such as vcf, bed, xls, tab limited matrix text file,
      CNVnator raw output and Gene fusion raw output, to plot circular view of the
      sample data. CGDV take cares of generating intermediate files required for
      circos. CGDV is freely available at https://cgdv-upload.persistent.co.in/cgdv/ .
      CONCLUSION: The circular plot for each data type is tailored to gain best
      biological insights into the data. The inter-relationship between data points,
      homologous sequences, genes involved in fusion events, differential expression
      pattern, sequencing depth, types and size of variations and enrichment of DNA
      binding proteins can be seen using CGDV. CGDV thus helps biologists and
      bioinformaticians to visualize a variety of genomics and transcriptomics data
      seamlessly.

PMID- 29065856
TI  - Factors associated to serum 25-hydroxyvitamin D levels among older adult
      populations in urban and suburban communities in Shanghai, China.
AB  - BACKGROUND: Vitamin D deficiency is widespread in China, particularly among older
      adults. Factors associated with suboptimal vitamin D levels are not well defined.
      The present study was a population-based study that included 10 urban and
      suburban communities in Shanghai, to evaluate vitamin D status and its correlates
      among older adults. METHOD: This cross-sectional study was based on study data
      for 3924 healthy men and women aged 65-95 years. Anthropometric and socioeconomic
      data were collected in June-July 2014. Serum 25(OH)D levels were detected using a
      chemiluminescence immunoassay. The following socioeconomic data were obtained
      through self-administered questionnaires: education level, lifestyle, residency,
      and dietary habits. A logistic regression model was used to assess associations
      between anthropometric factors, socioeconomic factors and serum 25(OH)D levels.
      RESULTS: Median levels of serum 25(OH)D in men and women were 22.73 and 19.99
      ng/mL, respectively. Vitamin D deficiency was common in subjects, even though
      data collection was conducted during summer. The general prevalence of serum
      25(OH)D levels <20 ng/mL were 35.4% and 50.5% for men and women respectively. The
      general prevalence of serum 25(OH)D levels <10 ng/mL were 2.73% and 5.9% for men
      and women respectively. A multivariable model indicated serum 25(OH)D levels >=20
      ng/mL were significantly and positively correlated with male sex, calcium or
      vitamin D supplementation, and residency in suburban communities. The model also
      indicated that high level of physical activity was protective factors of vitamin
      D deficiency for men and milk consumption for women, respectively. By contrast,
      deficient serum 25(OH)D levels were significantly correlated with education level
      (lower than primary school) or obesity [body mass index (BMI) >= 26.06 kg/m2] for
      men or women, respectively. CONCLUSION: This cross-sectional study of older
      adults in communities in Shanghai demonstrates that key factors positively
      correlated with serum 25(OH)D levels >=20 ng/mL include male sex, residency in
      suburban communities, calcium or vitamin D supplementation, high physical
      activity and education level (for men), and dairy consumption and maintenance of
      normal BMI (for women).

PMID- 29065858
TI  - A heuristic model for computational prediction of human branch point sequence.
AB  - BACKGROUND: Pre-mRNA splicing is the removal of introns from precursor mRNAs (pre
      mRNAs) and the concurrent ligation of the flanking exons to generate mature mRNA.
      This process is catalyzed by the spliceosome, where the splicing factor 1 (SF1)
      specifically recognizes the seven-nucleotide branch point sequence (BPS) and the
      U2 snRNP later displaces the SF1 and binds to the BPS. In mammals, the degeneracy
      of BPS motifs together with the lack of a large set of experimentally verified
      BPSs complicates the task of BPS prediction in silico. RESULTS: In this paper, we
      develop a simple and yet efficient heuristic model for human BPS prediction based
      on a novel scoring scheme, which quantifies the splicing strength of putative
      BPSs. The candidate BPS is restricted exclusively within a defined BPS search
      region to avoid the influences of other elements in the intron and therefore the
      prediction accuracy is improved. Moreover, using two types of relative
      frequencies for human BPS prediction, we demonstrate our model outperformed other
      current implementations on experimentally verified human introns. CONCLUSION: We
      propose that the binding energy contributes to the molecular recognition involved
      in human pre-mRNA splicing. In addition, a genome-wide human BPS prediction is
      carried out. The characteristics of predicted BPSs are in accordance with
      experimentally verified human BPSs, and branch site positions relative to the
      3'ss and the 5'end of the shortened AGEZ are consistent with the results of
      published papers. Meanwhile, a webserver for BPS predictor is freely available at
      http://biocomputer.bio.cuhk.edu.hk/BPS .

PMID- 29065860
TI  - Assessment of Haemostasis in patients undergoing emergent neurosurgery by
      rotational Elastometry and standard coagulation tests: a prospective
      observational study.
AB  - BACKGROUND: Rotational elastometry (ROTEM) has been shown useful to monitor
      coagulation in trauma patients and in major elective surgery. In this study, we
      aimed to evaluate the utility of ROTEM to identify hemostatic disturbances and to
      predict the need for transfusion, compared with standard coagulation tests (SCTs)
      in patients undergoing emergent neurosurgery. METHODS: Over a four-year period,
      adult patients who met criteria for emergent neurosurgery lasting more than 90
      min were included in the study. Blood was collected preoperatively and analyzed
      with SCTs (international normalized ratio [INR], fibrinogen concentration,
      prothrombin time [PT or Quick], partial thromboplastine time [PTT], fibrinogen
      concentration and platelet count), and ROTEM assays. Correlations between SCTs
      and ROTEM parameters as well as receiver operating characteristic curves were
      performed to detect a coagulopathic pattern based on standard criteria and the
      need for transfusing at least 3 units of packed red blood cells (PRBCs). RESULTS:
      In a cohort of 92 patients, 39 (42%) required >=3 PRBCs and a coagulopathic
      pattern was identified in 32 patients based on SCTs and in 19 based on ROTEM.
      There was a strong correlation between PTT and INTEM coagulation time (R = 0.76)
      as well as between fibrinogen concentrations and FIBTEM maximal clot firmess (R =
      0.70). The need for transfusion (>= 3 PRBCs) was best predicted by the maximal
      clot firmess of EXTEM and FIBTEM (AUC of 0.72 and 0.71, respectively) and by
      fibrinogen concentration (AUC of 0.70). CONCLUSIONS: In patients undergoing
      emergent neurosurgery, ROTEM analysis provides valid markers of early
      coagulopathy and predictors of blood transfusion requirements.

PMID- 29065859
TI  - Identification of copy number variation in French dairy and beef breeds using
      next-generation sequencing.
AB  - BACKGROUND: Copy number variations (CNV) are known to play a major role in
      genetic variability and disease pathogenesis in several species including cattle.
      In this study, we report the identification and characterization of CNV in eight
      French beef and dairy breeds using whole-genome sequence data from 200 animals.
      Bioinformatics analyses to search for CNV were carried out using four different
      but complementary tools and we validated a subset of the CNV by both in silico
      and experimental approaches. RESULTS: We report the identification and
      localization of 4178 putative deletion-only, duplication-only and CNV regions,
      which cover 6% of the bovine autosomal genome; they were validated by two in
      silico approaches and/or experimentally validated using array-based comparative
      genomic hybridization and single nucleotide polymorphism genotyping arrays. The
      size of these variants ranged from 334 bp to 7.7 Mb, with an average size of ~ 54
      kb. Of these 4178 variants, 3940 were deletions, 67 were duplications and 171
      corresponded to both deletions and duplications, which were defined as potential
      CNV regions. Gene content analysis revealed that, among these variants, 1100
      deletions and duplications encompassed 1803 known genes, which affect a wide
      spectrum of molecular functions, and 1095 overlapped with known QTL regions.
      CONCLUSIONS: Our study is a large-scale survey of CNV in eight French dairy and
      beef breeds. These CNV will be useful to study the link between genetic
      variability and economically important traits, and to improve our knowledge on
      the genomic architecture of cattle.

PMID- 29065862
TI  - Correction to: effects of dietary gelatin hydrolysates on bone mineral density in
      magnesium-deficient rats.

PMID- 29065861
TI  - Clinical effects of direct hemoperfusion using a polymyxin B-immobilized fiber
      column in clinically amyopathic dermatomyositis-associated rapidly progressive
      interstitial pneumonias.
AB  - BACKGROUND: Rapidly progressive interstitial pneumonias (RPIPs) associated with
      clinically amyopathic dermatomyositis (CADM) are highly resistant to therapy and
      have a poor prognosis. Multimodal therapies, including direct hemoperfusion using
      a polymyxin B-immobilized fiber column (PMX-DHP), have a protective effect on
      RPIPs. We evaluated the effects of PMX-DHP on CADM-associated RPIPs. METHODS: We
      retrospectively enrolled 14 patients with CADM-associated RPIPs and acute
      respiratory failure treated with PMX-DHP, corticosteroids, and immunosuppressive
      agents. Clinical manifestations were compared between survivors and non-survivors
      at 90 days after PMX-DHP. RESULTS: The survival rate at 90 days after PMX-DHP was
      35.7% (5/14). Before PMX-DHP, the survivor group exhibited a significantly higher
      PaO2/FiO2 (P/F) ratio and serum surfactant protein-D (SP-D) levels and
      significantly lower lactate dehydrogenase (LDH) and ferritin levels than the non
      survivor group. Platelet counts were significantly decreased after PMX-DHP
      therapy in both groups, but remained higher in the survivor group than the non
      survivor group over the course of treatment. Anti-melanoma differentiation
      associated gene 5 (MDA-5) antibody positive patients demonstrated a poor 90-day
      survival rate, lower platelet counts and P/F ratio, and higher LDH levels than
      anti-MDA-5 antibody negative patients. CONCLUSIONS: CADM-associated RPIPs with
      anti-MDA-5 antibody is associated with a very poor prognosis. A higher P/F ratio
      and SP-D level, lower LDH and ferritin levels, higher platelet counts, and anti
      MDA-5 antibody negativity are important prognostic markers in patients with CADM
      associated RPIPs treated with PMX-DHP.

PMID- 29065863
TI  - Obesity and socioeconomic disadvantage in midlife female public sector employees:
      a cohort study.
AB  - BACKGROUND: The two-way relationship between obesity and socioeconomic
      disadvantage is well established but previous studies on social and economic
      consequences of obesity have primarily focused on relatively young study
      populations. We examined whether obesity is associated with socioeconomic
      disadvantage through the 10-12-year follow-up, and how obesity-related
      socioeconomic inequalities develop during midlife among women. METHODS: Baseline
      data were derived from the female population of the Helsinki Health Study cohort,
      comprising 40-60 -year-old employees of the City of Helsinki, Finland in 2000
      2002 (n = 6913, response rate 69%). The follow-up surveys were carried out in
      2007 (n = 5810) and 2012 (n = 5400). Socioeconomic disadvantage was measured by
      five dichotomous measures. Repeated logistic regression analyses utilising
      generalized estimating equations (GEE) were used to test the association between
      baseline self-reported obesity and the likelihood of socioeconomic disadvantage
      through all phases. The effect of time on the development of inequalities was
      examined by time interaction terms in random effect logistic regression models.
      RESULTS: After adjustment for educational level, baseline obesity was associated
      with repeated poverty (OR = 1.23; 95% CI; 1.05-1.44), frequent economic
      difficulties (OR = 1.74; 95% CI; 1.52-1.99), low household net income (OR = 1.23;
      95% CI; 1.07-1.41), low household wealth (OR = 1.90; 95% CI; 1.59-2.26) and low
      personal income (OR = 1.22; 95% CI; 1.03-1.44). The differences in poverty rate
      and low personal income between the participants with obesity and participants
      with normal weight widened during the follow-up. Living without a partner and
      early exit from paid employment explained the widening of inequalities.
      CONCLUSIONS: Weight status inequalities in socioeconomic disadvantage persisted
      or widened during the late adulthood.

PMID- 29065864
TI  - Do some anxiety disorders belong to the prodrome of bipolar disorder? A clinical
      study combining retrospective and prospective methods to analyse the relationship
      between anxiety disorder and bipolar disorder from the perspective of biorhythms.
AB  - BACKGROUND: In clinical practice, some patients diagnosed with anxiety disorder
      (AD) may develop bipolar disorder (BD) many years later, and some cases of AD may
      be cured by the use of mood stabilizers. However, the relationship between AD and
      BD should be explored further. METHOD: To track how many cases of AD turned to BD
      and to discover the differences between them, we recruited 48 patients diagnosed
      with BD, who were assigned to the BD group for the retrospective analysis, and we
      also recruited 186 patients diagnosed with AD at enrolment; this latter group was
      asked to complete follow-up surveys conducted 3 months, 6 months, 12 months and
      18 months after the primary stage of the study. We defined another two groups
      according to the usage of mood stabilizers, the rates of reduction in scores on
      the Hamilton Anxiety Scale and Yale-Brown Obsessive Compulsive Scale, and the
      changes in Clinical Global Impression scores at different follow-up times: the
      anxiety group and the atypical BD group (who used mood stabilizers to treat AD).
      All subjects also completed the NEO Five-Factor Inventory and supplied blood
      samples to be tested for several endocrine indices (TSH, T3, FT3, T4, FT4,
      ACTH,PTC) and inflammatory cytokines (IL-6, IL-8, IL-10, TNF-alpha, CRP) at
      enrolment. RESULTS: In total, 14 subjects developed BD by the end of the study.
      One hundred eleven subjects were included in the anxiety group. Sixty-three
      subjects were assigned to the atypical BD group, and they had similar features to
      the 48 subjects in the BD group in terms of personality traits, abnormality rates
      of endocrine indices and levels of inflammatory cytokines. From the anxiety group
      to the atypical BD group and then the BD group, the age of first onset gradually
      decreased, while the frequency of onset and the score of suicidal ideation
      gradually increased. Furthermore, the atypical BD group showed markedly higher
      levels of TSH, IL-6, TNF-alpha and CRP than the other two groups. CONCLUSIONS:
      Some ADs with unique features might belong to the prodromal stage or the atypical
      presentation of BD, and recognizing these ADs early will economize many medical
      resources.

PMID- 29065865
TI  - Effectiveness and safety of exenatide in Korean patients with type 2 diabetes
      inadequately controlled with oral hypoglycemic agents: an observational study in
      a real clinical practice.
AB  - BACKGROUND: Randomized clinical trials have shown the efficacy and safety of
      short-acting exenatide in patients with type 2 diabetes mellitus (T2DM). The aim
      of this observational study was to investigate the effectiveness and safety of
      exenatide twice a day in Korean patients with T2DM who are suboptimally
      controlled with oral hypoglycemic agents. METHODS: This study was a post hoc
      analysis of multi-center (71 centers), prospective, observational, single-arm,
      post-marketing study of short-acting exenatide 5 to 10 MUg twice a day from March
      2008 to March 2014 and analyzed those who finished the follow-up over 20 weeks of
      medication. Changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and
      body weight values before and after exenatide treatment were analyzed. Adverse
      events and adverse drug reactions were estimated in patients who were treated
      with exenatide at least once and for whom follow-up for safety has been
      completed. RESULTS: After 20 weeks treatment with exenatide, mean HbA1c and body
      weight were significantly reduced from 8.4% to 7.7% and from 83.4 kg to 80.2 kg,
      respectively (both p < 0.001). Subjects with higher baseline glucose and HbA1c
      levels showed an independent association with a greater reduction in glucose
      level. In addition, short duration of diabetes less than 5 years was an
      independent predictor for the improvement in glucose level. The majority of study
      subjects showed a reduction in both body weight and glucose level (63.3%) after
      exenatide treatment. In terms of safety profile, exenatide treatment was
      generally well-tolerated and the incidence of severe adverse event was rare
      (0.8%). The gastrointestinal side effects were most common and hypoglycemia was
      reported in 1.7% of subjects. CONCLUSION: In real clinical practice, 20 weeks
      treatment with short-acting exenatide was well tolerated and showed a significant
      body weight and glucose reduction in Korean patients with T2D who are
      suboptimally controlled with oral hypoglycemic agents. TRIAL REGISTRATION:
      ClinicalTirals.gov , number NCT02090673 , registered 14 February 2008.

PMID- 29065866
TI  - Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and
      macrovascular complications.
AB  - BACKGROUND: Adipose tissue, an endocrine organ of the body, is involved in some
      obesity-related disease states such as insulin resistance, diabetes mellitus, and
      atherosclerosis. Vaspin is a novel adipocyte with insulin sensitizing effects. In
      this study, we planned to estimate serum vaspin concentrations as related to
      glycemic status and the presence of macrovascular complications among elderly
      patients with type-2 diabetes mellitus (T2DM). METHODS: A total of 230 elderly
      patients with T2DM were evaluated. These patients were divided into two groups:
      patients without complications (T2DM group, n = 110), and patients with
      macrovascular complications (T2DM + MC group, n = 120). In addition, 60 healthy
      elderly subjects were enrolled and assigned into the control group (NC group).
      Relevant parameters were matched for age and gender ratio. Serum vaspin
      concentrations were measured by Enzyme-linked immunosorbent assay (ELISA).
      Anthropometric measurements, plasma glucose and HbA1C levels, insulin
      concentration, liver and kidney functions, and lipid profile were measured for
      each participant. RESULTS: Serum vaspin concentrations were significantly higher
      in the T2DM group than in the T2DM + MC group (F = 13.122, P < 0.01). These
      concentrations were also significantly higher among females, compared to males (T
      = 3.567, P < 0.05). Logistic regression analysis revealed that serum vaspin
      concentration, systolic blood pressure, HDL-C and T2DM duration were independent
      influencing factors for diabetic macrovascular complications. CONCLUSION: Serum
      vaspin may be considered as a potential marker to assess the status of elderly
      patients with T2DM and the risk of developing serious macrovascular
      complications. Further prospective studies are warranted. TRIAL REGISTRATION:
      ChiCTR-OPC-14005698 , retrospectively registered on 20 Dec. 2014.

PMID- 29065867
TI  - The relative risk of second primary cancers in Austria's western states: a
      retrospective cohort study.
AB  - BACKGROUND: Cancer survivors are at risk of developing a second primary cancer
      (SPC) later in life because of persisting effects of genetic and behavioural risk
      factors, the long-term sequelae of chemotherapy, radiotherapy and the passage of
      time. This is the first study with Austrian data on an array of entities,
      estimating the risk of SPCs in a population-based study by calculating
      standardized incidence ratios (SIRs). METHODS: This retrospective cohort study
      included all invasive incident cancer cases diagnosed within the years 1988 to
      2005 being registered in the Tyrol and Vorarlberg Cancer Registries. Person years
      at risk (PYAR) were calculated from time of first diagnosis plus 2 months until
      the exit date, defined as the date of diagnosis of the SPC, date of death, or end
      of 2010, whichever came first. SIR for specific SPCs was calculated based on the
      risk of these patients for this specific cancer. RESULTS: A total of 59,638
      patients were diagnosed with cancer between 1988 and 2005 and 4949 SPCs were
      observed in 399,535 person-years of follow-up (median 5.7 years). Overall,
      neither males (SIR 0.90; 95% CI 0.86-0.93) nor females (SIR 1.00; 95% CI 0.96
      1.05) had a significantly increased SIR of developing a SPC. The SIR for SPC
      decreased with age showing a SIR of 1.24 (95% CI 1.12-1.35) in the age group of
      15-49 and a SIR of 0.85 (95% CI 0.82-0.89) in the age group of >= 65. If the site
      of the first primary cancer was head/neck/larynx cancer in males and females (SIR
      1.88, 95% CI 1.67-2.11 and 1.74, 95% CI 1.30-2.28), cervix cancer in females (SIR
      1.40, 95% CI 1.14-1.70), bladder cancer in males (SIR 1.20, 95% CI 1.07-1.34),
      kidney cancer in males and females (SIR 1.22, 95% 1.04-1.42 and 1.29, 95% CI 1.03
      1.59), thyroid gland cancer in females (SIR 1.40, 95% CI 1.11-1.75), patients
      showed elevated SIR, developing a SPC. CONCLUSIONS: Survivors of head & neck,
      bladder/kidney, thyroid cancer and younger patients show elevated SIRs,
      developing a SPC. This has possible implications for surveillance strategies.

PMID- 29065868
TI  - Using a very low-density SNP panel for genomic selection in a breeding program
      for sheep.
AB  - BACKGROUND: Building an efficient reference population for genomic selection is
      an issue when the recorded population is small and phenotypes are poorly
      informed, which is often the case in sheep breeding programs. Using stochastic
      simulation, we evaluated a genomic design based on a reference population with
      medium-density genotypes [around 45 K single nucleotide polymorphisms (SNPs)] of
      dams that were imputed from very low-density genotypes (<= 1000 SNPs). METHODS: A
      population under selection for a maternal trait was simulated using real
      genotypes. Genetic gains realized from classical selection and genomic selection
      designs were compared. Genomic selection scenarios that differed in reference
      population structure (whether or not dams were included in the reference) and
      genotype quality (medium-density or imputed to medium-density from very low
      density) were evaluated. RESULTS: The genomic design increased genetic gain by
      26% when the reference population was based on sire medium-density genotypes and
      by 54% when the reference population included both sire and dam medium-density
      genotypes. When medium-density genotypes of male candidates and dams were
      replaced by imputed genotypes from very low-density SNP genotypes (1000 SNPs),
      the increase in gain was 22% for the sire reference population and 42% for the
      sire and dam reference population. The rate of increase in inbreeding was lower
      (from - 20 to - 34%) for the genomic design than for the classical design
      regardless of the genomic scenario. CONCLUSIONS: We show that very low-density
      genotypes of male candidates and dams combined with an imputation process result
      in a substantial increase in genetic gain for small sheep breeding programs.

PMID- 29065869
TI  - Leading Comorbidity associated with 30-day post-anesthetic mortality in geriatric
      surgical patients in Taiwan: a retrospective study from the health insurance
      data.
AB  - BACKGROUND: Elderly patients with aged physical status and increased underlying
      disease suffered from more postoperative complication and mortality. We design
      this retrospective cohort study to investigate the relationship between existing
      comorbidity of elder patients and 30 day post-anesthetic mortality by using
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9-CM) from Health Insurance Database. METHODS: Patients aged above 65 years
      old who received anesthesia between 2000 and 2010 were included from 1 million
      Longitudinal Health Insurance Database in (LHID) 2005 in Taiwan. We use age, sex,
      type of surgery to calculate propensity score and match death group and survival
      one with 1:4 ratio (death: survival = 1401: 5823). Multivariate logistic model
      with stepwise variable selection was employed to investigate the factors
      affecting death 30 days after anesthesia. RESULTS: Thirty seven comorbidities can
      independently predict the post-anesthetic mortality. In our study, the leading
      comorbidities predict post-anesthetic mortality is chronic renal disease (OR =
      2.806), acute myocardial infarction (OR = 4.58), and intracranial hemorrhage (OR
      = 3.758). CONCLUSIONS: In this study, we present the leading comorbidity
      contributing to the postoperative mortality in elderly patients in Taiwan from
      National Health Insurance Database. Chronic renal failure is the leading
      contributing comorbidity of 30 days mortality after anesthesia in Taiwan which
      can be explained by the great number of hemodialysis and prolong life span under
      National Taiwan Health Insurance. Large scale database can offer enormous
      information which can help to improve quality of medical care.

PMID- 29065870
TI  - Crucial factors preceding compulsory psychiatric admission: a qualitative patient
      record study.
AB  - BACKGROUND: Compulsory admissions have a strong effect on psychiatric patients
      and represent a deprivation of personal liberty. Although the rate of such
      admissions is tending to rise in several Western countries, there is little
      qualitative research on the mental health-care process preceding compulsory
      admission. The objective of the study was to identify crucial factors in the
      mental health-care process preceding compulsory admission of adult psychiatric
      patients. METHODS: This retrospective, qualitative multiple-case study was based
      on the patient records of patients with severe mental illness, mainly
      schizophrenia and other psychotic disorders. Twenty two patient records were
      analyzed. Patients' demographic and clinical characteristics were heterogeneous.
      All were treated by Flexible Assertive Community Treatment teams (FACT teams) at
      two mental health institutions in the greater Rotterdam area in the Netherlands
      and had a compulsory admission in a predefined inclusion period. The data were
      analyzed according to the Prevention and Recovery System for Monitoring and
      Analysis (PRISMA) method, assessing acts, events, conditions, and circumstances,
      failing protective barriers and protective recovery factors. RESULTS: The most
      important patient factors in the process preceding compulsory admission were
      psychosis, aggression, lack of insight, care avoidance, and unauthorized
      reduction or cessation of medication. Neither were health-care professionals as
      assertive as they could be in managing early signs of relapse and care avoidance
      of these particular patients. CONCLUSION: The health-care process preceding
      compulsory admission is complex, being influenced by acts, events, conditions and
      circumstances, failing barriers, and protective factors. The most crucial factors
      are patients' lack of insight and cessation of medication, and health-care
      professionals' lack of assertiveness.

PMID- 29065871
TI  - Q&A: Cellular near death experiences-what is anastasis?
AB  - Apoptosis is a form of programmed cell death that is carried out by proteolytic
      enzymes called caspases. Executioner caspase activity causes cells to shrink,
      bleb, and disintegrate into apoptotic bodies and has been considered a point of
      no return for apoptotic cells. However, relatively recent work has shown that
      cells can survive transient apoptotic stimuli, even after executioner caspase
      activation. This process is called anastasis. In this Q&A, we answer common
      questions that arise regarding anastasis, including how it is defined, the origin
      of the name, the potential physiological consequences, molecular mechanisms, and
      open questions for this new field of study.

PMID- 29065873
TI  - High variability of TB, HIV, hepatitis C treatment and opioid substitution
      therapy among prisoners in Germany.
AB  - BACKGROUND: In Germany, medical care of prisoners is completely separated from
      extramural health care. The extent and quality of medical care among prisoners in
      Germany are therefore largely unknown. We performed a secondary data analysis of
      pharmacy sales data for tuberculosis (TB), HIV, hepatitis C (HCV) and opioid
      substitution treatment (OST) delivered to prisons in 11 federal states (FS) in
      Germany between 01/2012 and 03/2013. The aims of this study were to assess (i)
      the treatment availability for the selected diseases and OST in German prisons,
      (ii) the proportion of prisoners treated per FS and overall for TB, HIV, HCV and
      OST during the study period. METHODS: Substances unique to or typically used for
      the treatment of each disease were defined as marker substances with defined
      daily doses (DDD). For each marker substance we assessed the cumulative number of
      DDD, the average daily number of DDD (DDDd) and average treatment prevalence per
      day in percent (adTP). Accordingly, the DDDd represents one person treated per
      day and the adTP means the proportion of prisoners treated per day. We compared
      the adTP of the diseases with previously measured prevalences. RESULTS: We
      obtained data from pharmacies supplying prisons in 11 of 16 German FS. Of the
      included prisons, 41% were supplied with medicines for TB, 71% for HIV and 58%
      for HCV and OST. Twice as many delivered marker substances for TB were indicated
      for the continuation phase and chemoprevention than the intensive phase. The HIV
      adTP ranged from 0.06% to 0.94%, HCV adTP ranged from 0.03% to 0.59% and OST adTP
      ranged from 0% to 7.90%. The overall adTP for the respective treatment was 0.39%
      for HIV, 0.12% for HCV and 2.18% for OST. CONCLUSIONS: According to our findings
      treatment rates for TB were consistent with the expected TB prevalence, at least
      in Berlin. HIV treatment seems to be offered to an adequate proportion of
      estimated infected prisoners. In contrast, the HCV treatment prevalence was low.
      High variation among FS in provision of all treatments, particularly of OST,
      point to inconsistent treatment practices, although nationwide extramural
      treatment guidelines for Germany exist.

PMID- 29065872
TI  - QuaDMutEx: quadratic driver mutation explorer.
AB  - BACKGROUND: Somatic mutations accumulate in human cells throughout life. Some may
      have no adverse consequences, but some of them may lead to cancer. A cancer
      genome is typically unstable, and thus more mutations can accumulate in the DNA
      of cancer cells. An ongoing problem is to figure out which mutations are drivers 
      play a role in oncogenesis, and which are passengers - do not play a role. One
      way of addressing this question is through inspection of somatic mutations in DNA
      of cancer samples from a cohort of patients and detection of patterns that
      differentiate driver from passenger mutations. RESULTS: We propose QuaDMutEx, a
      method that incorporates three novel elements: a new gene set penalty that
      includes non-linear penalization of multiple mutations in putative sets of driver
      genes, an ability to adjust the method to handle slow- and fast-evolving tumors,
      and a computationally efficient method for finding gene sets that minimize the
      penalty, through a combination of heuristic Monte Carlo optimization and exact
      binary quadratic programming. Compared to existing methods, the proposed
      algorithm finds sets of putative driver genes that show higher coverage and lower
      excess coverage in eight sets of cancer samples coming from brain, ovarian, lung,
      and breast tumors. CONCLUSIONS: Superior ability to improve on both coverage and
      excess coverage on different types of cancer shows that QuaDMutEx is a tool that
      should be part of a state-of-the-art toolbox in the driver gene discovery
      pipeline. It can detect genes harboring rare driver mutations that may be missed
      by existing methods. QuaDMutEx is available for download from
      https://github.com/bokhariy/QuaDMutEx under the GNU GPLv3 license.

PMID- 29065874
TI  - Measurement invariance testing of the PHQ-9 in a multi-ethnic population in
      Europe: the HELIUS study.
AB  - BACKGROUND: In Western European countries, the prevalence of depressive symptoms
      is higher among ethnic minority groups, compared to the host population. We
      explored whether these inequalities reflect variance in the way depressive
      symptoms are measured, by investigating whether items of the PHQ-9 measure the
      same underlying construct in six ethnic groups in the Netherlands. METHODS: A
      total of 23,182 men and women aged 18-70 of Dutch, South-Asian Surinamese,
      African Surinamese, Ghanaian, Turkish or Moroccan origin were included in the
      HELIUS study and had answered to at least one of the PHQ-9 items. We conducted
      multiple group confirmatory factor analyses (MGCFA), with increasingly stringent
      model constraints (i.e. assessing Configural, Metric, Strong and Strict
      measurement invariance (MI)), and regression analysis, to confirm comparability
      of PHQ-9 items across ethnic groups. RESULTS: A one-factor model, where all nine
      items reflect a single underlying construct, showed acceptable model fit and was
      used for MI testing. In each subsequent step, change in goodness-of-fit measures
      did not exceed 0.015 (RMSEA) or 0.01 (CFI). Moreover, strict invariance models
      showed good or acceptable model fit (Men: RMSEA = 0.050; CFI = 0.985; Women:
      RMSEA = 0.058; CFI = 0.979), indicating between-group equality of item clusters,
      factor loadings, item thresholds and residual variances. Finally, regression
      analysis did not indicate potential ethnicity-related differential item
      functioning (DIF) of the PHQ-9. CONCLUSIONS: This study provides evidence of
      measurement invariance of the PHQ-9 regarding ethnicity, implying that the
      observed inequalities in depressive symptoms cannot be attributed to DIF.

PMID- 29065875
TI  - A randomised trial of the influence of racial stereotype bias on examiners'
      scores, feedback and recollections in undergraduate clinical exams.
AB  - BACKGROUND: Asian medical students and doctors receive lower scores on average
      than their white counterparts in examinations in the UK and internationally (a
      phenomenon known as "differential attainment"). This could be due to examiner
      bias or to social, psychological or cultural influences on learning or
      performance. We investigated whether students' scores or feedback show influence
      of ethnicity-related bias; whether examiners unconsciously bring to mind
      (activate) stereotypes when judging Asian students' performance; whether
      activation depends on the stereotypicality of students' performances; and whether
      stereotypes influence examiner memories of performances. METHODS: This is a
      randomised, double-blinded, controlled, Internet-based trial. We created near
      identical videos of medical student performances on a simulated Objective
      Structured Clinical Exam using British Asian and white British actors. Examiners
      were randomly assigned to watch performances from white and Asian students that
      were either consistent or inconsistent with a previously described stereotype of
      Asian students' performance. We compared the two examiner groups in terms of the
      following: the scores and feedback they gave white and Asian students; how much
      the Asian stereotype was activated in their minds (response times to Asian
      stereotypical vs neutral words in a lexical decision task); and whether the
      stereotype influenced memories of student performances (recognition rates for
      real vs invented stereotype-consistent vs stereotype-inconsistent phrases from
      one of the videos). RESULTS: Examiners responded to Asian-stereotypical words
      (716 ms, 95% confidence interval (CI) 702-731 ms) faster than neutral words (769
      ms, 95% CI 753-786 ms, p < 0.001), suggesting Asian stereotypes were activated
      (or at least active) in examiners' minds. This occurred regardless of whether
      examiners observed stereotype-consistent or stereotype-inconsistent performances.
      Despite this stereotype activation, student ethnicity had no influence on
      examiners' scores; on the feedback examiners gave; or on examiners' memories for
      one performance. CONCLUSIONS: Examiner bias does not appear to explain the
      differential attainment of Asian students in UK medical schools. Efforts to
      ensure equality should focus on social, psychological and cultural factors that
      may disadvantage learning or performance in Asian and other minority ethnic
      students.

PMID- 29065877
TI  - Postoperative C-reactive protein/albumin ratio as a novel predictor for short
      term complications following gastrectomy of gastric cancer.
AB  - BACKGROUND: Postoperative complications following gastric cancer resection remain
      a clinical problem. Early detection of postoperative complications is needed
      before critical illness develops. The purpose of this study was to evaluate the
      prognostic value of C-reactive protein/albumin ratio in patients with gastric
      cancer. METHODS: A total of 322 patients undergoing curative (R0) gastrectomy
      between 2015 and 2017 were retrospectively analyzed. Univariate and multivariate
      analyses were performed to identify clinical factors predicting postoperative
      complications. The cutoff values and diagnostic accuracy of C-reactive
      protein/albumin ratio and C-reactive protein were determined by receiver
      operating characteristic curves. RESULTS: Among all of the patients, 85 (26.4%)
      developed postoperative complications. The optimal cutoff of C-reactive
      protein/albumin ratio was set at 3.04 based on the ROC analysis. Multivariate
      analysis identified C-reactive protein/albumin ratio was an independent risk
      factors for complications after gastrectomy (OR 3.037; 95% CI 1.248-7.392; P =
      0.014). Additionally, C-reactive protein/albumin ratio showed a higher diagnostic
      accuracy than C-reactive protein on postoperative day 3 (AUC: 0.685 vs 0.660;
      sensitivity: 0.624 vs 0.471; specificity: 0.722 vs 0.835). CONCLUSIONS: Elevated
      C-reactive protein/albumin ratio was an independent predictor for postoperative
      complications following gastrectomy of gastric cancer, and the diagnostic
      accuracy was higher than C-reactive protein alone. Overall, postoperative C
      reactive protein/albumin ratio may help to identify patients with high
      probability of postoperative complications.

PMID- 29065876
TI  - Nanomaterials modulate stem cell differentiation: biological interaction and
      underlying mechanisms.
AB  - Stem cells are unspecialized cells that have the potential for self-renewal and
      differentiation into more specialized cell types. The chemical and physical
      properties of surrounding microenvironment contribute to the growth and
      differentiation of stem cells and consequently play crucial roles in the
      regulation of stem cells' fate. Nanomaterials hold great promise in biological
      and biomedical fields owing to their unique properties, such as controllable
      particle size, facile synthesis, large surface-to-volume ratio, tunable surface
      chemistry, and biocompatibility. Over the recent years, accumulating evidence has
      shown that nanomaterials can facilitate stem cell proliferation and
      differentiation, and great effort is undertaken to explore their possible
      modulating manners and mechanisms on stem cell differentiation. In present
      review, we summarize recent progress in the regulating potential of various
      nanomaterials on stem cell differentiation and discuss the possible cell uptake,
      biological interaction and underlying mechanisms.

PMID- 29065878
TI  - Mutants of Yarrowia lipolytica NCIM 3589 grown on waste cooking oil as a
      biofactory for biodiesel production.
AB  - BACKGROUND: Oleaginous yeasts are fast emerging as a possible feedstock for
      biodiesel production. Yarrowia lipolytica, a model oleaginous yeast is known to
      utilize a variety of hydrophobic substrates for lipid accumulation including
      waste cooking oil (WCO). Approaches to increase lipid content in this yeast
      include metabolic engineering which requires manipulation of multiple genes in
      the lipid biosynthesis pathway. A classical and cost-effective approach, namely,
      random chemical mutagenesis on the yeast can lead to increased production of
      biodiesel as is explored here. RESULTS: In this study, chemical mutagenesis using
      the alkylating agent, N- methyl-N'-nitro-N-nitrosoguanidine (MNNG) as well as an
      additional treatment with cerulenin, a fatty acid synthase inhibitor generated
      800 mutants of Y. lipolytica NCIM 3589 (761 MNNG treated and 39 MNNG + cerulenin
      treated). A three-stage screening using Sudan Black B plate technique, Nile red
      fluorimetry and total lipid extraction using solvent was performed, which enabled
      selection of ten high lipid yielding mutants. Time course studies of all the ten
      mutants were further undertaken in terms of biomass, lipid yield and lipid
      content to select three stable mutants (YlB6, YlC7 and YlE1) capable of growing
      and accumulating lipid on WCO, with lipid contents of 55, 60 and 67% as compared
      to 45% for the wild type. The mutants demonstrated increased volumetric lipid
      productivities (0.062, 0.044 and 0.041 g L-1 h-1) as compared to the wild type
      (0.033 g L-1 h-1). The fatty acid profile of the three mutants consisted of a
      high content of C16 and C18 saturated and monounsaturated fatty acids and was
      found to be suitable for biodiesel production. The fuel properties, namely,
      density, kinematic viscosity, total acid number, iodine value of the three
      mutants were evaluated and found to lie within the limits specified by
      internationally accepted standards. Additionally, it was noted that the mutants
      demonstrated better cetane numbers and higher heating values than the wild type
      strain. CONCLUSION: The chemical mutagenesis strategy adopted in this study
      resulted in the successful isolation of three stable high SCO yielding mutants.
      The mutants, namely, YlB6, YlC7 and YlE1 exhibited a 1.22, 1.33 and 1.49-fold
      increase in lipid contents when grown on 100 g L-1 waste cooking oil than the
      parental yeast strain. The fatty acid methyl ester (FAME) profiles of all the
      three mutants was determined to be suitable for biodiesel suggesting their
      potential applicability while simultaneously addressing the management of waste
      cooking oil.

PMID- 29065879
TI  - Impact of surgical resection extension on outcome for primary well-differentiated
      thyroid cancer-a retrospective analysis.
AB  - BACKGROUND: The surgical resection extension in well-differentiated thyroid
      cancer is controversially discussed with the possibility of an overtreatment on
      the one hand against the risk of local disease recurrence. The aim of this study
      is to evaluate how the surgical resection extension with the adjunction of
      radioiodine therapy affects postoperative morbidity and the oncologic outcome of
      patients primarily treated for well-differentiated thyroid cancer. METHODS: All
      patients undergoing primary surgery for a well-differentiated, non-recurrent
      thyroid cancer from January 2005 to April 2013 at Tuebingen University Hospital
      were retrospectively analyzed. RESULTS: Papillary thyroid cancer (PTC) was
      present in 73 patients (including 27 papillary microcarinoma) and follicular
      thyroid cancer in 14 patients. Fifty-six of 87 patients (64%) underwent one-stage
      surgery, of which 26 patients (30%) received simultaneous lymph node dissection
      (LND). The remaining 31 patients (36%) underwent a two-stage completion surgery
      (29 patients with LND). Only in three patients a single lymph node metastasis was
      newly detected during two-stage completion surgery. Patients with LND at either
      one-stage and two-stage completion surgery had a significant higher rate of
      transient postoperative hypocalcemia. Postoperative adjuvant radioiodine therapy
      was performed in 68 of 87 patients (78%). After a median follow-up of 69 months
      [range 9-104], one local recurrence was documented in a patient suffering from
      PTC 23 months after surgery. CONCLUSION: No prophylactic two-stage
      lymphadenectomy should be performed in case of well-differentiated thyroid cancer
      to avoid unnecessary complication without any proven oncologic benefit.

PMID- 29065880
TI  - Identification and utilization of two important transporters: SgvT1 and SgvT2,
      for griseoviridin and viridogrisein biosynthesis in Streptomyces griseoviridis.
AB  - BACKGROUND: Griseoviridin (GV) and viridogrisein (VG, also referred as etamycin),
      both biosynthesized by a distinct 105 kb biosynthetic gene cluster (BGC) in
      Streptomyces griseoviridis NRRL 2427, are a pair of synergistic streptogramin
      antibiotics and very important in treating infections of many multi-drug
      resistant microorganisms. Three transporter genes, sgvT1-T3 have been discovered
      within the 105 kb GV/VG BGC, but the function of these efflux transporters have
      not been identified. RESULTS: In the present study, we have identified the
      different roles of these three transporters, SgvT1, SgvT2 and SgvT3. SgvT1 is a
      major facilitator superfamily (MFS) transporter whereas SgvT2 appears to serve as
      the sole ATP-binding cassette (ABC) transporter within the GV/VG BGC. Both
      proteins are necessary for efficient GV/VG biosynthesis although SgvT1 plays an
      especially critical role by averting undesired intracellular GV/VG accumulation
      during biosynthesis. SgvT3 is an alternative MFS-based transporter that appears
      to serve as a compensatory transporter in GV/VG biosynthesis. We also have
      identified the gamma-butyrolactone (GBL) signaling pathway as a central regulator
      of sgvT1-T3 expression. Above all, overexpression of sgvT1 and sgvT2 enhances
      transmembrane transport leading to steady production of GV/VG in titers ~ 3-fold
      greater than seen for the wild-type producer and without any notable disturbances
      to GV/VG biosynthetic gene expression or antibiotic control. CONCLUSIONS: Our
      results shows that SgvT1-T2 are essential and useful in GV/VG biosynthesis and
      our effort highlight a new and effective strategy by which to better exploit
      streptogramin-based natural products of which GV and VG are prime examples with
      clinical potential.

PMID- 29065881
TI  - The implications of ritual practices and ritual plant uses on nature
      conservation: a case study among the Naxi in Yunnan Province, Southwest China.
AB  - BACKGROUND: Conservation of biodiversity is primary important of today's
      critically vulnerable environment. Efficient conservation can be possible only
      with the long-term participation and understanding of the communities. Ritual
      beliefs of the indigenous people are one of the important tools to understand the
      local communities and aid the nature conservation. In this paper, we documented
      contemporary ritual practices and ritual plant uses among the Naxi people and
      discussed the importance of traditional knowledge on ritual practice in the
      conservation of plants in the mountains presenting a case study of the Dongba
      culture. METHODS: This study was carried out from July in 2013 to July in 2014.
      To document and analyze the present state of the ritual plant used by the Naxi
      people we conducted an ethnobotanical survey. We interviewed local people
      including Dongba priests using the semi-structured questionnaire. During the
      field study, we participated in the local religious activities to witness the use
      of different plants in ritual activities of the Naxi people. We interviewed
      twenty-two key informants and eleven of them were male. All the specimens of
      documented species were collected and deposited at the herbarium of Kunming
      Institute of Botany. RESULTS: The survey results revealed the Naxi people
      possessed sound knowledge of the traditional ritual plants and great diversity of
      plants used in many of Naxi rituals and festivals. From the survey, we documented
      32 ritual plant species belonging to 24 genera of 17 families used in various
      ritual activities. The ritual plants were grouped into two categories, namely
      those burned as incense, and those used for decoration. The incense plants like
      Olea europaea subsp. cuspidata and Pistacia weinmanniifolia were probably
      promising natural aromatic resource. Plants of genus Quercus were the most
      frequently used species. The places for ritual activities were diverse, such as
      the incense burners inside and outside the house and sacred trees at the
      Baishuitai. Local people except the young generation had an abundant of
      traditional knowledge. CONCLUSIONS: Our study shows the live ritual activities
      and the beliefs of the residents are keeping the plant diversity and the entire
      forest preserved as sacred mountains. Our study emphasizes traditional belief and
      an alternative view of conservation that is not led mainly by governmental
      policies, as local practices and ritual plants uses play as constant reminders to
      the Naxi on nature conservation. However, further research is recommended for in
      depth understanding the role of traditional belief in biodiversity conservation.

PMID- 29065882
TI  - Frequency of G6PD Mediterranean in individuals with and without malaria in
      Southern Pakistan.
AB  - BACKGROUND: Pakistan has an estimated annual burden of 1.5 million malaria cases.
      The current situation calls for an effective malaria control and eradication
      programme in this country. Currently, primaquine is an attractive option for
      eliminating reservoirs of Plasmodium vivax hypnozoites and killing gametocytes of
      Plasmodium falciparum. However, this drug causes haemolysis in individuals who
      are glucose-6-phosphate (G6PD) deficient. It is important to map G6PD deficiency
      and malaria distribution in Pakistan to design an effective malaria eradication
      regimen. Frequency of G6PD deficiency (G6PDd) in malaria patients has not been
      reported from Pakistan in any meaningful way. The purpose of this study was to
      evaluate the frequency of G6PD c.563C>T (G6PD Mediterranean) in male individuals
      with and without falciparum malaria. METHODS: Two hundred and ten archived DNA
      samples from males (110 from falciparum malaria patients and 100 from healthy
      individuals) were utilized in this study. Healthy blood donors were selected
      based on stringent pre-defined criteria. Patients were confirmed for malaria
      parasites on microscopy and or immune chromatographic assay detecting P.
      falciparum histidine-rich protein 2. Parasitaemia was also computed. DNA samples
      were tested for G6PD c.563C>T mutation through PCR-RFLP according to the
      previously defined protocol and its allelic frequency was computed. RESULTS: G6PD
      c.563C>T was observed in four of 110 patients with falciparum malaria and in two
      of 100 healthy donors. Mean (+/- SD) haemoglobin, median (IQR) platelet and
      median (IQR) parasite count in G6PD-deficient malaria-patients were 8.9 +/- 0.9
      g/dL, 124 * 109/L (IQR 32, 171) and 57,920/MUL of blood (IQR 12,920, 540,000)
      respectively. CONCLUSIONS: Cumulative allelic frequency for G6PD 563c.C>T was
      0.0285 detected in 6 of 210 X-chromosomes in Southern Pakistan. Frequency for
      this G6PD allele was 0.0364 in malaria-patients and 0.0200 in healthy
      individuals. Large studies including females are needed to elucidate the true
      burden of G6PDd in malaria-endemic areas. The information will enable local
      health policy makers to design effective strategies for eliminating malaria form
      this region.

PMID- 29065883
TI  - Chronic hepatitis B carriers with acute on chronic liver failure show increased
      HBV surface gene mutations, including immune escape variants.
AB  - BACKGROUND: The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic
      hepatitis B (CHB) is not well understood. The aim of this study was to
      investigate whether there is an association between HBV polymerase
      (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC)
      variants and development of ACLF in CHB. METHODS: Two CHB patient cohorts were
      compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12
      HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9
      genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal
      sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV
      diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and
      mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each
      group. RESULTS: Our data showed the incidence of IE and clusters of mutations in
      the HBV S region was significantly greater in ACLF patients vs. treatment naive
      CHB patients (p < 0.05). Additionally, a significantly higher frequency of G1896A
      and A1762T/G1764A mutations were found in HBeAg negative than in ACLF patients (p
      < 0.0001). CONCLUSION: In our study, ACLF was not associated with a specific
      genomic mutation. However, higher frequency of IE mutations along with various
      mutations clustering in the HBV S region could contribute to or be an outcome of
      ACLF in CHB infection. (words 226).

PMID- 29065884
TI  - Risk factors and pregnancy outcomes associated with placental malaria in a
      prospective cohort of Papua New Guinean women.
AB  - BACKGROUND: Plasmodium falciparum in pregnancy results in substantial poor health
      outcomes for both mother and child, particularly in young, primigravid mothers
      who are at greatest risk of placental malaria (PM) infection. Complications of PM
      include maternal anaemia, low birth weight and preterm delivery, which contribute
      to maternal and infant morbidity and mortality in coastal Papua New Guinea (PNG).
      METHODS: Placental biopsies were examined from 1451 pregnant women who were
      enrolled in a malaria prevention study at 14-26 weeks gestation. Clinical and
      demographic information were collected at first antenatal clinic visits and women
      were followed until delivery. Placental biopsies were collected and examined for
      PM using histology. The presence of infected erythrocytes and/or the malaria
      pigment in monocytes or fibrin was used to determine the type of placental
      infection. RESULTS: Of 1451 placentas examined, PM infection was detected in 269
      (18.5%), of which 54 (3.7%) were acute, 55 (3.8%) chronic, and 160 (11.0%) were
      past infections. Risk factors for PM included residing in rural areas (adjusted
      odds ratio (AOR) 3.65, 95% CI 1.76-7.51; p <= 0.001), being primigravid (AOR
      2.45, 95% CI 1.26-4.77; p = 0.008) and having symptomatic malaria during
      pregnancy (AOR 2.05, 95% CI 1.16-3.62; p = 0.013). After adjustment for
      covariates, compared to uninfected women, acute infections (AOR 1.97, 95% CI 0.98
      3.95; p = 0.056) were associated with low birth weight babies, whereas chronic
      infections were associated with preterm delivery (AOR 3.92, 95% CI 1.64-9.38; p =
      0.002) and anaemia (AOR 2.22, 95% CI 1.02-4.84; p = 0.045). CONCLUSIONS: Among
      pregnant PNG women receiving at least one dose of intermittent preventive
      treatment in pregnancy and using insecticide-treated bed nets, active PM
      infections were associated with adverse outcomes. Improved malaria prevention is
      required to optimize pregnancy outcomes.

PMID- 29065885
TI  - Serum bilirubin and the risk of chronic obstructive pulmonary disease
      exacerbations.
AB  - BACKGROUND: Bilirubin is a potent anti-oxidant and higher serum concentrations of
      bilirubin have been associated with better lung function, slower lung function
      decline, and lower incidence of chronic obstructive pulmonary disease (COPD). We
      sought to determine whether elevated bilirubin blood concentrations are
      associated with lower risk for acute exacerbations of COPD (AECOPD). METHODS: We
      performed a secondary analyses of data in the Simvastatin for Prevention of
      Exacerbations in Moderate-to-Severe COPD (STATCOPE) and the Azithromycin for
      Prevention of Exacerbations of COPD (MACRO) studies. We used time-dependent
      multivariable Cox proportional hazards analyses, using bilirubin concentrations
      prior to first AECOPD as the exposure variable and time to first AECOPD as the
      outcome variable. STATCOPE was used for model development, with validation in
      MACRO. RESULTS: In STATCOPE (n = 853), higher bilirubin was associated with a
      lower but statistically insignificant hazard for AECOPD, (adjusted hazard ratio
      [aHR] 0.89 per log10 increase [95%CI: 0.74 to 1.09; p = 0.26]). In the validation
      MACRO study (n = 1018), higher bilirubin was associated with a significantly
      lower hazard for AECOPD (aHR 0.80 per log10 increase [95%CI: 0.67 to 0.94; p =
      0.008]). CONCLUSIONS: Bilirubin may be a biomarker of AECOPD risk and may be a
      novel therapeutic target to reduce AECOPD risk. TRIAL REGISTRATIONS:
      ClinicalTrials.gov NCT01061671 (registered 02 February 2010) and
      ClinicalTrials.gov NCT00325897 (registered 12 May 2006).

PMID- 29065886
TI  - A summary index for antimicrobial resistance in food animals in the Netherlands.
AB  - BACKGROUND: The Dutch government has set targets for reduction of antimicrobial
      usage in food animals, stipulating a 50% reduction in usage (on a weight basis)
      in 2013 as compared to 2009 and a 70% decrease in 2015. A monitoring program has
      been instituted to evaluate the impact on antimicrobial resistance (AMR). The
      Dutch Ministry of Public Health Welfare and Sports has expressed the need for a
      summary index to present the results of the monitoring data concisely to policy
      makers. METHODS: We use data on AMR in bacteria from randomly collected samples
      from broiler chickens, fattening pigs, veal calves and dairy cows. Escherichia
      coli was selected for resistance monitoring because they are intrinsically
      susceptible to the antibiotics included in the test panel (ciprofloxacin,
      cefotaxime, tetracycline and ampicillin) and they are present in all samples,
      which facilitates proper randomization and trend analysis. The AMR summary index
      was calculated for each animal species as a weighted average over the four
      antibiotics, taking into account their clinical relevance. Weights were obtained
      by conjoint analysis, a pairwise comparison study involving infectious diseases
      professionals with clinical and public health backgrounds, with data analysis by
      conditional logistic regression. The AMR summary index was then computed by Monte
      Carlo simulation, accounting for sampling and regression uncertainty. RESULTS:
      The highest weights (0.35) were given to ciprofloxacin and cefotaxime followed by
      ampicillin (0.23) and tetracycline (0.07). Throughout the years, the AMR index
      was highest in broiler chickens, followed by pigs and veal calves, while the
      lowest values were consistently recorded in dairy cows. In all animal species,
      the index in 2014 was significantly lower than in 2009. CONCLUSIONS: We
      demonstrate that high-dimensional data on surveillance of antimicrobial
      resistance can be summarized in an index for evaluating trends between and within
      food animal species by a process involving decision makers and scientists to
      select and weight the most relevant antibiotics.

PMID- 29065887
TI  - Computed tomography of the thorax in rabbits: a prospective study in ten
      clinically healthy New Zealand White rabbits.
AB  - BACKGROUND: Literature investigating the normal cross-sectional anatomy of
      rabbits with computed tomography (CT) is sparse and incomplete. The purpose of
      the present study was to investigate the normal thoracic structures, in
      particular the cranial thorax, with CT angiography in 10 clinically healthy New
      Zealand White (NZW) rabbits. RESULTS: Absolute and relative measurements of the
      trachea, heart, thoracic caudal vena cava and aorta, right and left principal
      bronchi, right and left caudal lobar bronchi and the accompanying branches of the
      right and left pulmonary artery and vein, right and left lung volume and lung
      density were taken. The three lobes of the thymus (right ventral, right dorsal
      and left thoracic lobes) were identified in all rabbits. Both the right dorsal
      and left thoracic lobes of the thymus extended between the heart and thoracic
      wall in all individuals with the left lobe reaching more caudally in seven
      animals. Consequently, the craniocaudal extension of the left lung was smaller
      than the right lung in these rabbits. Volume of the left lung was significantly
      smaller than the right (P = 0.005). The cranial mediastinal, right and left
      tracheobronchial and the aortic thoracic lymph nodes were very small and
      identified in four, four, seven and ten rabbits, respectively. The heart took up
      a median of 4.0 intercostal spaces, and in seven rabbits, it was located in the
      2nd-5th intercostal space. Median relative cardiac height and width measured 74
      and 88%, respectively. The median angle of the trachea to the spine was 5 degrees
      . Median density between the right and left lung did not significantly differ (-
      549 and - 583 Hounsfield units, respectively). In all but one rabbit, atelectasis
      was present and classified as mild, moderate or severe in six, two and one
      individuals, respectively. Mild subclinical bronchopneumonia was diagnosed in
      seven rabbits. CONCLUSIONS: The present study provides species-specific
      anatomical CT information and reference values for structures in the thorax of
      the NZW rabbit. Subclinical bronchopneumonia appears to be a common CT finding.

PMID- 29065889
TI  - Injury induced expression of caveolar proteins in human kidney tubules - role of
      megakaryoblastic leukemia 1.
AB  - BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These
      organelles, composed of caveolin and cavin proteins, are important for cellular
      signaling and survival. Caveolae play incompletely defined roles in human
      kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described
      previously, but the responsible mechanism remains to be defined. METHODS: Healthy
      and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3
      and cavin 1-4) and examined by electron microscopy. Induction of caveolar
      proteins was studied in isolated proximal tubules and primary renal epithelial
      cells. These cells were challenged with hypoxia or H2O2. Primary tubular cells
      were also subjected to viral overexpression of megakaryoblastic leukemia 1 (MKL1)
      and MKL1 inhibition by the MKL1 inhibitor CCG-1423. Putative coregulators of MKL1
      activity were investigated by Western blotting for suppressor of cancer cell
      invasion (SCAI) and filamin A (FLNA). Finally, correlative bioinformatic studies
      of mRNA expression of caveolar proteins and MKL1 were performed. RESULTS: In
      healthy kidneys, caveolar proteins were expressed by the parietal epithelial
      cells (PECs) of Bowman's capsule, endothelial cells and vascular smooth muscle.
      Electron microscopy confirmed caveolae in the PECs. No expression was seen in
      proximal tubules. In contrast, caveolar proteins were expressed in proximal
      tubules undergoing atrophy. Caveolar proteins were also induced in cultures of
      primary epithelial tubular cells. Expression was not enhanced by hypoxia or free
      radical stress (H2O2), but proved sensitive to inhibition of MKL1. Viral
      overexpression of MKL1 induced caveolin-1/CAV1, caveolin-2/CAV2 and SDPR/CAVIN2.
      In kidney tissue, the mRNA level of MKL1 correlated with the mRNA levels for
      caveolin-1/CAV1, caveolin-2/CAV2 and the archetypal MKL1 target tenascin C (TNC),
      as did the MKL1 coactivator FLNA. Costaining for TNC as readout for MKL1 activity
      demonstrated overlap with caveolin-1/CAV1 expression in PECs as well as in
      atrophic segments of proximal tubules. CONCLUSIONS: Our findings support the view
      that MKL1 contributes to the expression of caveolar proteins in healthy kidneys
      and orchestrates the induction of tubular caveolar proteins in renal injury.

PMID- 29065890
TI  - The mediating effects of childhood neglect on the association between schizotypal
      and autistic personality traits and depression in a non-clinical sample.
AB  - BACKGROUND: Autistic personality traits (APT) and schizotypal personality traits
      (SPT) are associated with depression. However, mediating factors within these
      relationships have not yet been explored. Thus, the focus of the current study
      was to examine the effects of childhood neglect on the relationship between
      APT/SPT and depression. METHODS: This cross-sectional study was conducted on
      first-year students (N = 2469) at Hunan University of Chinese Medicine and
      Hengyang Normal College (Changsha, China). Participants completed surveys on APT,
      SPT, childhood neglect, abuse and depression. RESULTS: Through correlational
      analyses, APT and SPT traits were positively correlated with childhood neglect
      and depression (p < 0.05). In a hierarchical regression analysis, among types of
      childhood maltreatment, emotional neglect (beta = 0.112, p < 0.001) and physical
      neglect (beta = 0.105, p < 0.001) were the strongest predictors of depression.
      Childhood neglect did not account for the relationships between APT/SPT and
      depression. Further analysis found that childhood neglect mediated the
      relationship between SPT and depression but not APT and depression. CONCLUSIONS:
      Among types of childhood maltreatment, neglect was the strongest predicting
      factor for depression. Neglect did not account for the relationship between
      APT/SPT and depression but was a strong mediating factor between SPT and
      depression.

PMID- 29065891
TI  - Correction to: Selective episiotomy vs. implementation of a non-episiotomy
      protocol: a randomized clinical trial.

PMID- 29065888
TI  - A comprehensive data mining study shows that most nuclear receptors act as newly
      proposed homeostasis-associated molecular pattern receptors.
AB  - BACKGROUND: Nuclear receptors (NRs) can regulate gene expression; therefore, they
      are classified as transcription factors. Despite the extensive research carried
      out on NRs, still several issues including (1) the expression profile of NRs in
      human tissues, (2) how the NR expression is modulated during atherosclerosis and
      metabolic diseases, and (3) the overview of the role of NRs in inflammatory
      conditions are not fully understood. METHODS: To determine whether and how the
      expression of NRs are regulated in physiological/pathological conditions, we took
      an experimental database analysis to determine expression of all 48 known NRs in
      21 human and 17 murine tissues as well as in pathological conditions. RESULTS: We
      made the following significant findings: (1) NRs are differentially expressed in
      tissues, which may be under regulation by oxygen sensors, angiogenesis pathway,
      stem cell master regulators, inflammasomes, and tissue hypo-/hypermethylation
      indexes; (2) NR sequence mutations are associated with increased risks for
      development of cancers and metabolic, cardiovascular, and autoimmune diseases;
      (3) NRs have less tendency to be upregulated than downregulated in cancers, and
      autoimmune and metabolic diseases, which may be regulated by inflammation
      pathways and mitochondrial energy enzymes; and (4) the innate immune sensor
      inflammasome/caspase-1 pathway regulates the expression of most NRs. CONCLUSIONS:
      Based on our findings, we propose a new paradigm that most nuclear receptors are
      anti-inflammatory homeostasis-associated molecular pattern receptors (HAMPRs).
      Our results have provided a novel insight on NRs as therapeutic targets in
      metabolic diseases, inflammations, and malignancies.

PMID- 29065892
TI  - The value of blood cytokines and chemokines in assessing COPD.
AB  - BACKGROUND: Blood biomarkers are increasingly used to stratify high risk chronic
      obstructive pulmonary disease (COPD) patients; however, there are fewer studies
      that have investigated multiple biomarkers and replicated in multiple large well
      characterized cohorts of susceptible current and former smokers. METHODS: We used
      two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects
      from COPDGene and 1117 subjects from SPIROMICS. These biomarkers included:
      interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha,
      interferon (IFN)-gamma, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and
      activation-regulated chemokine (TARC)/CCL-17. Regression models adjusted for
      clinical covariates were used to determine which biomarkers were associated with
      the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s
      (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD
      exacerbations, and emphysema. Biomarker-genotype associations were assessed by
      genome-wide association of single nucleotide polymorphisms (SNPs). RESULTS:
      Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted
      for 3-5% of the measurement variance on top of clinical variables. IL-6 was
      associated with progressive airflow obstruction over 5 years and both IL-6 and IL
      8 were associated with progressive emphysema over 5 years. None of the biomarkers
      were consistently associated with chronic bronchitis or COPD exacerbations. We
      identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma
      measurements. CONCLUSION: When assessing smoking related pulmonary disease,
      biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add
      additional modest predictive value on top of clinical variables alone. TRIAL
      REGISTRATION: COPDGene (ClinicalTrials.gov Identifier: NCT02445183 ).
      Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (
      ClinicalTrials.gov Identifier: NCT 01969344 ).

PMID- 29065893
TI  - Neuropsychological and internalizing problems in acute central nervous system
      infections: a 1 year follow-up.
AB  - BACKGROUND: Acute central nervous system (ACNS) infections such as meningitis,
      encephalitis and cerebellitis still cause morbidity and mortality among children.
      The aim of this study was to verify whether neuropsychological impairment may
      develop in ACNS survivors. METHODS: The study included pediatric patients
      affected by ACNS disorders, aged 3-16 years admitted to the Bambino Gesu Children
      Hospital, Rome from June 2013 till June 2015. The patients and their parents
      underwent a psychological interview and neuropsychological tests during the first
      week of hospital admission and 1 year after, during a follow-up control. Wilcoxon
      signed rank tests for paired data were conducted to verify if the results were
      statistically importance. Patients underwent a cognitive profile test through the
      Leiter international performance scale - revised, motor skills evaluation through
      the test of visual-motor integration and a psychopathological evaluation by the
      child behavior checklist. The K-SADS-PL test was administered in children 6-11
      years old to check psychopathological disorders. RESULTS: Forty-four patients
      were included in the study. At the 1 year follow-up, "anxiety problems"
      (dependency, fears, worries, nervousness) developed in 47% of patients, "somatic
      problems" (aches, headaches, nausea, vomiting) in 29% and "affective problems"
      (crying, self-harming, worthlessness, guilt, tiredness, sadness) in 29%. Visual
      perception was statistically increased at the 1 year follow-up in our patient
      cohort (p = 0.0297), mainly among the meningitides group (p = 0.0189). Motor
      coordination also increased at the follow-up check in the study participants (p =
      0.0076), especially in the group affected by cerebellitis (p = 0.0302).
      CONCLUSIONS: Neuropsychological disorders are often difficult to recognize in the
      early stage. They must, however, be promptly identified through specific and
      standardized neuropsychological examinations in order to avoid long term sequelae
      in adulthood.

PMID- 29065894
TI  - A 'Grantathon' model to mentor new investigators in mental health research.
AB  - BACKGROUND: There is a critical gap between needs and available resources for
      mental health treatment across the world, particularly in low- and middle-income
      countries (LMICs). In countries committed to increasing resources to address
      these needs it is important to conduct research, not only to assess the depth of
      mental health needs and the current provision of public and private mental health
      services, but also to examine implementation methods and evaluate mental health
      approaches to determine which methods are most effective in local contexts.
      However, research resources in many LMICs are inadequate, largely because
      conventional research training is time-consuming and expensive. Adapting a
      hackathon model may be a feasible method of increasing capacity for mental health
      services research in resource-poor countries. METHODS: To explore the feasibility
      of this approach, we developed a 'grantathon', i.e. a research training workshop,
      to build capacity among new investigators on implementation research of Indian
      government-funded mental health programmes, which was based on a need expressed
      by government agencies. The workshop was conducted in Delhi, India, and brought
      together junior faculty members working in mental health services settings
      throughout the country, experienced international behavioural health researchers
      and representatives of the Indian Council for Medical Research (ICMR), the prime
      Indian medical research funding agency. Pre- and post-assessments were used to
      capture changes in participants' perceived abilities to develop proposals, design
      research studies, evaluate outcomes and develop collaborations with ICMR and
      other researchers. Process measures were used to track the number of single-or
      multi-site proposals that were generated and funded. RESULTS: Participants (n =
      24) generated 12 single- or multi-site research grant applications that will be
      funded by ICMR. CONCLUSION: The grantathon model described herein can be modified
      to build mental health services research capacity in other contexts. Given that
      this workshop not only was conceptualised and delivered but also returned results
      in less than 1 year, this model has the potential to quickly build research
      capacity and ultimately reduce the mental health treatment gap in resource
      limited settings.

PMID- 29065895
TI  - Associations between community-based physiotherapy for musculoskeletal injury and
      health related quality of life (EQ-5D): a multi-centre retrospective analysis.
AB  - BACKGROUND: Community-based musculoskeletal physiotherapy is used to improve
      function and health related quality of life (HRQoL). The purpose of this
      retrospective, multi-centre observational study was to determine the association
      between community-based physiotherapy management for musculoskeletal disorders
      and changes in HRQoL. METHODS: Four thousand one hundred twelve patients' data
      were included in the study. Patients were included if they received a single
      period of treatment for a musculoskeletal injury or disorder. Patients were only
      included if they were being treated for a single morbidity. Patients received
      standard physiotherapy appropriate to their specific disorder, which could
      include health education/advice, exercise therapy, manual therapy, taping, soft
      tissue techniques, electrotherapy and/or acupuncture. Health related quality of
      life was assessed using the EQ-5D index. RESULTS: EQ-5D improved by 0.203 across
      all patients (d = 1.10). When grouped by anatomical site of symptom, the largest
      increases in EQ-5D was in foot pain (0.233; d = 1.29) and lumbar pain (0.231; d =
      1.13). Improvements in EQ-5D greater than the minimum clinically important
      difference (MCID) were seen in 68.4% of all patients. The highest proportion of
      patients with positive responses to treatment were in ankle pain (74.2%) and
      thoracic pain (73.4%). The hand (40.5%), elbow (34.7%), and hip (33.9%) showed
      the greatest proportion of patients that did not respond to treatment.
      CONCLUSIONS: Community-based musculoskeletal physiotherapy is associated with
      improved health related quality of life. A randomised controlled trial is needed
      to determine any causal relationship between community-based physiotherapy and
      health related quality of life improvements.

PMID- 29065896
TI  - Harm reduction principles for healthcare settings.
AB  - BACKGROUND: Harm reduction refers to interventions aimed at reducing the negative
      effects of health behaviors without necessarily extinguishing the problematic
      health behaviors completely. The vast majority of the harm reduction literature
      focuses on the harms of drug use and on specific harm reduction strategies, such
      as syringe exchange, rather than on the harm reduction philosophy as a whole.
      Given that a harm reduction approach can address other risk behaviors that often
      occur alongside drug use and that harm reduction principles have been applied to
      harms such as sex work, eating disorders, and tobacco use, a natural evolution of
      the harm reduction philosophy is to extend it to other health risk behaviors and
      to a broader healthcare audience. METHODS: Building on the extant literature, we
      used data from in-depth qualitative interviews with 23 patients and 17 staff
      members from an HIV clinic in the USA to describe harm reduction principles for
      use in healthcare settings. RESULTS: We defined six principles of harm reduction
      and generalized them for use in healthcare settings with patients beyond those
      who use illicit substances. The principles include humanism, pragmatism,
      individualism, autonomy, incrementalism, and accountability without termination.
      For each of these principles, we present a definition, a description of how
      healthcare providers can deliver interventions informed by the principle, and
      examples of how each principle may be applied in the healthcare setting.
      CONCLUSION: This paper is one of the firsts to provide a comprehensive set of
      principles for universal harm reduction as a conceptual approach for healthcare
      provision. Applying harm reduction principles in healthcare settings may improve
      clinical care outcomes given that the quality of the provider-patient
      relationship is known to impact health outcomes and treatment adherence. Harm
      reduction can be a universal precaution applied to all individuals regardless of
      their disclosure of negative health behaviors, given that health behaviors are
      not binary or linear but operate along a continuum based on a variety of
      individual and social determinants.

PMID- 29065897
TI  - Associations of the perceived and objective neighborhood environment with
      physical activity and sedentary time in New Zealand adolescents.
AB  - BACKGROUND: There is accumulating evidence supporting the association between
      neighborhood built environments and adults' physical activity (PA) and sedentary
      time (ST); however, few studies have investigated these associations in
      adolescents. A better understanding of the features of the built environment that
      encourage PA or ST is therefore of critical importance to promote health and
      wellbeing in adolescents. The aim of this study was to estimate the associations
      of GIS-determined and perceived walkability components in individual residential
      buffer zones with accelerometer-assessed moderate-to-vigorous physical activity
      (MVPA) and ST in adolescents. METHODS: The Built Environment in Adolescent New
      Zealanders (BEANZ) study was conducted in two cities (Auckland and Wellington)
      during the 2013-2014 academic school years. The exposure measures were subjective
      and objective environmental indices of activity-friendliness using four
      residential buffers. Road network buffers were calculated around participant's
      residential addresses using the sausage buffer approach at 250 m, 500 m, 1 km,
      and 2 km scales. A 25 m radius was used for the buffers. Data were analysed using
      Generalized Additive Mixed Models in R. RESULTS: Data were analysed from 524
      participants (15.78 +/- 1.62 years; 45% male). Participants accumulated ~114
      min/day of moderate-to-vigorous PA (MVPA) and ~354 min/day of ST during
      accelerometer wear-time (~828 min/day). The estimated difference in MVPA between
      participants with the 1st and 3rd quartiles observed values on the composite
      subjective environmental index of activity-friendliness (perceived land use mix -
      diversity, street connectivity and aesthetics) was equivalent to ~8 min/day (~56
      MVPA min/week) and for the objective environmental index of activity-friendliness
      (gross residential density and number of parks within 2 km distance from home)
      was ~6 min of MVPA/day (~45 MVPA min/week). When both indices were entered in a
      main-effect model, both indices remained significantly correlated with MVPA with
      sex as a moderator. The predicted difference in sedentary time between those with
      the minimum and maximum observed values on the subjective index of non
      sedentariness was ~20 min/day. CONCLUSIONS: The combined assessment of the main
      effects of subjective and objective indices of activity-friendliness on NZ
      adolescents' PA and ST showed positive relationships with MVPA for the subjective
      index only. The subjective index was a significant correlate of PA in both girls
      and boys, while the objective index was significant only in boys when sex was
      entered as a moderator. Further research is warranted to understand the
      relationships of ST with the built environment.

PMID- 29065899
TI  - Upper extremity open fractures in hospitalized road traffic accident patients:
      adult versus pediatric cases.
AB  - BACKGROUND: Fractures in pediatrics show epidemiological characteristics which
      are different from fractures in adults. The objective of this study was to
      examine the injury profiles of open upper extremity fractures (UEFs) in all modes
      of injury related to road traffic accidents (RTAs) in adult and pediatric
      hospitalized patients. METHODS: Data on 103,465 RTA patients between 1997 and
      2013 whose records were entered in a centralized country trauma database were
      reviewed. Data on open UEFs related to mode of injury (car, motorcycle, bicycle,
      and pedestrian) was compared between adult (18+ years) and pediatric (0-17 years)
      RTA patients. RESULTS: Of 103,465 RTA cases, 17,263 (16.7%) had UEFs. Of 73,087
      adults, 13,237 (18.1%) included UEFs and of 30,378 pediatric cases, 4026 (13.2%)
      included UEFs (p < 0.0001). Of 17,263 cases with UEFs, we reviewed 22,132
      fractures with 2, 743 (12.4%) open fractures. Adults had a greater risk for open
      fractures (2221, 13%) than the pediatric cases (522, 10.3%) (p < 0.0001).
      Overall, of a total of 22,132 UEFs, most of the fractures were in the radius
      (22.8%), humerus (20.3%), clavicle (17.5%), and ulna (15.4%). The adult
      pedestrian group had a significantly higher risk for open UEFs than the pediatric
      group (11 vs 8%, p = 0.0012). CONCLUSIONS: This study demonstrates the difference
      between adult and pediatric open fractures in hospitalized RTAs. We showed that
      adults had a greater risk for open UEFs compared to children, and the adult
      pedestrian group particularly had a significantly higher risk for open UEFs than
      the pediatric group.

PMID- 29065898
TI  - Comparative review of human and canine osteosarcoma: morphology, epidemiology,
      prognosis, treatment and genetics.
AB  - Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in
      dogs are 27 times higher than in people. Prognosis in both species is relatively
      poor, with 5 year OSA survival rates in people not having improved in decades.
      For dogs, 1 year survival rates are only around ~ 45%. Improved and novel
      treatment regimens are urgently required to improve survival in both humans and
      dogs with OSA. Utilising information from genetic studies could assist in this in
      both species, with the higher incidence rates in dogs contributing to the dog
      population being a good model of human disease. This review compares the clinical
      characteristics, gross morphology and histopathology, aetiology, epidemiology,
      and genetics of canine and human OSA. Finally, the current position of canine OSA
      genetic research is discussed and areas for additional work within the canine
      population are identified.

PMID- 29065900
TI  - GRcalculator: an online tool for calculating and mining dose-response data.
AB  - BACKGROUND: Quantifying the response of cell lines to drugs or other perturbagens
      is the cornerstone of pre-clinical drug development and pharmacogenomics as well
      as a means to study factors that contribute to sensitivity and resistance. In
      dividing cells, traditional metrics derived from dose-response curves such as IC
      50 , AUC, and E max , are confounded by the number of cell divisions taking place
      during the assay, which varies widely for biological and experimental reasons.
      Hafner et al. (Nat Meth 13:521-627, 2016) recently proposed an alternative way to
      quantify drug response, normalized growth rate (GR) inhibition, that is robust to
      such confounders. Adoption of the GR method is expected to improve the
      reproducibility of dose-response assays and the reliability of pharmacogenomic
      associations (Hafner et al. 500-502, 2017). RESULTS: We describe here an
      interactive website ( www.grcalculator.org ) for calculation, analysis, and
      visualization of dose-response data using the GR approach and for comparison of
      GR and traditional metrics. Data can be user-supplied or derived from published
      datasets. The web tools are implemented in the form of three integrated Shiny
      applications (grcalculator, grbrowser, and grtutorial) deployed through a Shiny
      server. Intuitive graphical user interfaces (GUIs) allow for interactive analysis
      and visualization of data. The Shiny applications make use of two R packages
      (shinyLi and GRmetrics) specifically developed for this purpose. The GRmetrics R
      package is also available via Bioconductor and can be used for offline data
      analysis and visualization. Source code for the Shiny applications and associated
      packages (shinyLi and GRmetrics) can be accessed at www.github.com/uc
      bd2k/grcalculator and www.github.com/datarail/gr_metrics . CONCLUSIONS:
      GRcalculator is a powerful, user-friendly, and free tool to facilitate analysis
      of dose-response data. It generates publication-ready figures and provides a
      unified platform for investigators to analyze dose-response data across diverse
      cell types and perturbagens (including drugs, biological ligands, RNAi, etc.).
      GRcalculator also provides access to data collected by the NIH LINCS Program (
      http://www.lincsproject.org /) and other public domain datasets. The GRmetrics
      Bioconductor package provides computationally trained users with a platform for
      offline analysis of dose-response data and facilitates inclusion of GR metrics
      calculations within existing R analysis pipelines. These tools are therefore well
      suited to users in academia as well as industry.

PMID- 29065902
TI  - Treatment of orofacial granulomatosis: a case report.
AB  - BACKGROUND: Orofacial granulomatosis is a relatively recent term coined by
      Wiesenfield et al. in 1985 to define granulomatous lesions of oral mucosa without
      intestinal involvement. When it presents in a triad encompassing facial nerve
      palsy, lip swelling, and fissured or furrowed tongue it is called Melkersson
      Rosenthal syndrome while monosymptomatic or oligosymptomatic forms are referred
      to as granulomatous cheilitis. It is an uncommon clinicopathologic entity which
      is distinct from classic Crohn's disease. The NOD2 variant which is commonly
      associated with Crohn's has not been shown to have any association with orofacial
      granulomatosis. CASE PRESENTATION: We present a case of a 31-year-old white man
      who had painful swelling of the lip with oral ulcers and difficulty eating for 2
      to 3 years. He was diagnosed as having granulomatous cheilitis based on
      characteristic biopsy findings. There was serologic evidence of Crohn's disease
      with anti-Saccharomyces cerevisiae antibodies. However, he was not found to have
      any gastrointestinal involvement based on computed tomography enterography, and
      upper and lower endoscopies. He failed to respond to nonsteroidal anti
      inflammatory drugs, steroids, and dapsone therapy but responded well to high
      doses of infliximab. CONCLUSIONS: Our case questions whether granulomatous
      cheilitis really exists or is it simply a variant of Crohn's disease with only
      oral presentation. Our patient did not have symptoms of Crohn's disease;
      moreover, endoscopic studies and computed tomography enterography were
      unremarkable for evidence of intestinal involvement. Our case is also the first
      reported case where high-dose infliximab alone has been used with sustained
      response for approximately 8 months. In conclusion, more research is needed to
      assess the underlying pathology as well as ideal treatment options for patients
      with orofacial granulomatosis. We propose that high-dose infliximab should be
      considered in patients who do not respond to traditional therapies.

PMID- 29065901
TI  - Predictive biological markers of systemic lupus erythematosus flares: a
      systematic literature review.
AB  - BACKGROUND: The aim of this study was to identify the most reliable biomarkers in
      the literature that could be used as flare predictors in systemic lupus
      erythematosus (SLE). METHODS: A systematic review of the literature was performed
      using two databases (MEDLINE and EMBASE) through April 2015 and congress
      abstracts from the American College of Rheumatology and the European League
      Against Rheumatism were reviewed from 2010 to 2014. Two independent reviewers
      screened titles and abstracts and analysed selected papers in detail, using a
      specific questionnaire. Reports addressing the relationships between one or more
      defined biological test(s) and the occurrence of disease exacerbation were
      included in the systematic review. RESULTS: From all of the databases, 4668
      records were retrieved, of which 69 studies or congress abstracts were selected
      for the systematic review. The performance of seven types of biomarkers performed
      routinely in clinical practice and nine types of novel biological markers was
      evaluated. Despite some encouraging results for anti-double-stranded DNA
      antibodies, anti-C1q antibodies, B-lymphocyte stimulator and tumour necrosis
      factor-like weak inducer of apoptosis, none of the biomarkers stood out from the
      others as a potential gold standard for flare prediction. The results were
      heterogeneous, and a lack of standardized data prevented us from identifying a
      powerful biomarker. CONCLUSIONS: No powerful conclusions could be drawn from this
      systematic review due to a lack of standardized data. Efforts should be
      undertaken to optimize future research on potential SLE biomarkers to develop
      validated candidates. Thus, we propose a standardized pattern for future studies.

PMID- 29065903
TI  - Changes in clinical disease activity are weakly linked to changes in MRI
      inflammation on treat-to-target escalation of therapy in rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) treat-to-target (T2T) regimens often use
      the disease activity score (28 joints) incorporating C-reactive protein
      (DAS28CRP) as an outcome measure. We compared changes in the DAS28CRP with
      changes in magnetic resonance imaging (MRI) inflammation on treatment escalation.
      METHODS: Eighty seropositive RA patients with active disease were enrolled. Group
      A (N = 57) escalated to another conventional disease-modifying therapy (cDMARD)
      combination, and Group B (N = 23) to anti-TNF therapy/cDMARDs. Contrast-enhanced
      3T-MRI wrist scans were obtained before and 4 months after regimen change. Scan
      pairs were scored for inflammation (MRI(i)) and damage. Disease activity was
      assessed using the DAS28CRP. RESULTS: Eighty patients were enrolled and 66 MRI
      scan pairs were available for analysis. Intra-reader reliability was high:
      intraclass correlation coefficient (average) 0.89 (0.56-0.97). DeltaDAS28CRP did
      not differ between groups: Group A, -0.94 (-3.30, 1.61); Group B, -1.53 (-3.59,
      0.56) (p = 0.45). DeltaMRI(i) also did not differ: Group A, 0 (-25, 10); Group B,
      -1 (-15, 28) (p = 0.12). Combining groups, DeltaMRI(i) correlated weakly with
      DeltaDAS28CRP (Spearman's 0.36, p = 0.003). Using multiple linear regression
      analysis adjusting for confounders, DeltaDAS28CRP was associated with DeltaMRI(i)
      (p = 0.056). Of the individual MRI measures, only Deltatenosynovitis correlated
      with DeltaDAS28CRP (Spearman's 0.33, p = 0.007). DeltaMRI(i) was negatively
      associated with the MRI erosion score at entry (p = 0.0052). CONCLUSIONS: We
      report the first study investigating the link between changes in clinical and
      imaging inflammation in a real-world RA cohort escalating to conventional and
      biologic DMARDs. The association was significant but relatively weak, suggesting
      that MRI targets cannot yet be advocated as outcomes for T2T escalation. TRIAL
      REGISTRATION: ANZCTR 12614000895684 . Registered 22 August 2014.

PMID- 29065904
TI  - Intrauterine device embedded in omentum of postpartum patient with a markedly
      retroverted uterus: a case report.
AB  - BACKGROUND: The intrauterine device is a popular form of long-acting reversible
      contraception. Although generally safe, one of the most serious complications of
      intrauterine device use is uterine perforation. Risk factors for perforation
      include position of the uterus, force exerted during intrauterine device
      insertion, postpartum period, and breastfeeding. This case is important and needs
      to be reported because it highlights the need to assess risk factors for uterine
      perforation. It adds to the medical literature because it examines the
      relationship between position of the uterus and the location of uterine
      perforation. This case report is unusual in that it describes the mechanism and
      specific location of uterine perforation in relation to the position of the
      uterus. CASE PRESENTATION: We present a case of an intrauterine device found in
      the omentum of a 30-year-old white postpartum woman with a significantly
      retroverted uterus after the intrauterine device threads were not visualized on
      speculum examination during a 6-week placement check. The intrauterine device was
      located and removed via laparoscopy without complication. CONCLUSIONS: This case
      report will be of interest to women's health practitioners because it illustrates
      the importance of identifying patients with risk factors for uterine perforation,
      examining the relationship between uterine position and location of perforation.
      This is especially significant because the true incidence of perforation may be
      higher than the numbers reported in the literature. There is no specific
      diagnostic code for uterine perforation and it is unlikely that retrospective
      studies can accurately identify all cases.

PMID- 29065905
TI  - Severe intestinal dysbiosis is prevalent in primary Sjogren's syndrome and is
      associated with systemic disease activity.
AB  - BACKGROUND: Altered microbial composition of the intestine, commonly referred to
      as dysbiosis, has been associated with several autoimmune diseases including
      primary Sjogren's syndrome (pSS). The aims of the current study were to study the
      intestinal microbial balance in pSS and to identify clinical features associated
      with dysbiosis. METHODS: Forty-two consecutive pSS patients and 35 age-matched
      and sex-matched control subjects were included in the study in an open clinic
      setting. Stool samples were analyzed for intestinal dysbiosis using a validated
      16S rRNA-based microbiota test (GA-mapTM Dysbiosis Test; Genetic Analysis, Oslo,
      Norway). Dysbiosis and severe dysbiosis were defined in accordance with the
      manufacturer's instructions. Patients were evaluated with regard to disease
      activity (European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease
      Activity Index (ESSDAI) and Clinical ESSDAI (ClinESSDAI)). In addition, patients
      were examined for laboratory and serological features of pSS as well as fecal
      calprotectin levels. Furthermore, patients were investigated regarding patient
      reported outcomes for pSS (EULAR Sjogren's Syndrome Patient Reported Index
      (ESSPRI)) and irritable bowel syndrome (IBS)-like symptoms according to the Rome
      III criteria. RESULTS: Severe dysbiosis was more prevalent in pSS patients in
      comparison to controls (21 vs 3%; p = 0.018). Subjects with pSS and severe
      dysbiosis had higher disease activity as evaluated by the ESSDAI total score (13
      vs 5; p = 0.049) and the ClinESSDAI total score (12 vs 5; p = 0.049), lower
      levels of complement component 4 (0.11 vs 0.17 g/L; p = 0.004), as well as higher
      levels of fecal calprotectin (110 vs 33 MUg/g; p = 0.001) compared to the other
      pSS patients. In contrast, severe dysbiosis among pSS patients was not associated
      with disease duration, IBS-like symptoms, or the ESSPRI total score. CONCLUSIONS:
      Severe intestinal dysbiosis is a prevalent finding in pSS and is associated both
      with clinical and laboratory markers of systemic disease activity as well as
      gastrointestinal inflammation. Further studies are warranted to elucidate a
      potential causative link between dysbiosis and pSS.

PMID- 29065906
TI  - Biological function integrated prediction of severe radiographic progression in
      rheumatoid arthritis: a nested case control study.
AB  - BACKGROUND: Radiographic progression is reported to be highly heritable in
      rheumatoid arthritis (RA). However, previous study using genetic loci showed an
      insufficient accuracy of prediction for radiographic progression. The aim of this
      study is to identify a biologically relevant prediction model of radiographic
      progression in patients with RA using a genome-wide association study (GWAS)
      combined with bioinformatics analysis. METHODS: We obtained genome-wide single
      nucleotide polymorphism (SNP) data for 374 Korean patients with RA using Illumina
      HumanOmni2.5Exome-8 arrays. Radiographic progression was measured using the
      yearly Sharp/van der Heijde modified score rate, and categorized in no or severe
      progression. Significant SNPs for severe radiographic progression from GWAS were
      mapped on the functional genes and reprioritized by post-GWAS analysis. For
      robust prediction of radiographic progression, tenfold cross-validation using a
      support vector machine (SVM) classifier was conducted. Accuracy was used for
      selection of optimal SNPs set in the Hanyang Bae RA cohort. The performance of
      our final model was compared with that of other models based on GWAS results and
      SPOT (one of the post-GWAS analyses) using receiver operating characteristic
      (ROC) curves. The reliability of our model was confirmed using GWAS data of
      Caucasian patients with RA. RESULTS: A total of 36,091 significant SNPs with a p
      value <0.05 from GWAS were reprioritized using post-GWAS analysis and
      approximately 2700 were identified as SNPs related to RA biological features. The
      best average accuracy of ten groups was 0.6015 with 85 SNPs, and this increased
      to 0.7481 when combined with clinical information. In comparisons of the
      performance of the model, the 0.7872 area under the curve (AUC) in our model was
      superior to that obtained with GWAS (AUC 0.6586, p value 8.97 * 10-5) or SPOT
      (AUC 0.7449, p value 0.0423). Our model strategy also showed superior prediction
      accuracy in Caucasian patients with RA compared with GWAS (p value 0.0049) and
      SPOT (p value 0.0151). CONCLUSIONS: Using various biological functions of SNPs
      and repeated machine learning, our model could predict severe radiographic
      progression relevantly and robustly in patients with RA compared with models
      using only GWAS results or other post-GWAS tools.

PMID- 29065907
TI  - Regulatory remodeling in the allo-tetraploid frog Xenopus laevis.
AB  - BACKGROUND: Genome duplication has played a pivotal role in the evolution of many
      eukaryotic lineages, including the vertebrates. A relatively recent vertebrate
      genome duplication is that in Xenopus laevis, which resulted from the
      hybridization of two closely related species about 17 million years ago. However,
      little is known about the consequences of this duplication at the level of the
      genome, the epigenome, and gene expression. RESULTS: The X. laevis genome
      consists of two subgenomes, referred to as L (long chromosomes) and S (short
      chromosomes), that originated from distinct diploid progenitors. Of the parental
      subgenomes, S chromosomes have degraded faster than L chromosomes from the point
      of genome duplication until the present day. Deletions appear to have the largest
      effect on pseudogene formation and loss of regulatory regions. Deleted regions
      are enriched for long DNA repeats and the flanking regions have high alignment
      scores, suggesting that non-allelic homologous recombination has played a
      significant role in the loss of DNA. To assess innovations in the X. laevis
      subgenomes we examined p300-bound enhancer peaks that are unique to one subgenome
      and absent from X. tropicalis. A large majority of new enhancers comprise
      transposable elements. Finally, to dissect early and late events following
      interspecific hybridization, we examined the epigenome and the enhancer landscape
      in X. tropicalis * X. laevis hybrid embryos. Strikingly, young X. tropicalis DNA
      transposons are derepressed and recruit p300 in hybrid embryos. CONCLUSIONS: The
      results show that erosion of X. laevis genes and functional regulatory elements
      is associated with repeats and non-allelic homologous recombination and
      furthermore that young repeats have also contributed to the p300-bound regulatory
      landscape following hybridization and whole-genome duplication.

PMID- 29065908
TI  - Utrophin influences mitochondrial pathology and oxidative stress in dystrophic
      muscle.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is a lethal X-linked muscle wasting
      disorder caused by the absence of dystrophin, a large cytoskeletal muscle
      protein. Increasing the levels of the dystrophin-related-protein utrophin is a
      highly promising therapy for DMD and has been shown to improve pathology in
      dystrophin-deficient mice. One contributing factor to muscle wasting in DMD is
      mitochondrial pathology that contributes to oxidative stress and propagates
      muscle damage. The purpose of this study was to assess whether utrophin could
      attenuate mitochondria pathology and oxidative stress. METHODS: Skeletal muscles
      from wildtype C57BL/10, dystrophin-deficient mdx, dystrophin/utrophin double
      knockout (dko) and dystrophin-deficient mdx/utrophin over-expressing mdx-Fiona
      transgenic mice were assessed for markers of mitochondrial damage. RESULTS: Using
      transmission electron microscopy, we show that high levels of utrophin ameliorate
      the aberrant structure and localisation of mitochondria in mdx mice whereas
      absence of utrophin worsened these features in dko mice. Elevated utrophin also
      reverts markers of protein oxidation and oxidative stress, elevated in mdx and
      dko mice, to wildtype levels. These changes were observed independently of a
      shift in oxidative phenotype. CONCLUSION: These findings show that utrophin
      levels influence mitochondrial pathology and oxidative stress. While utrophin
      deficiency worsens the pathology, utrophin over-expression in dystrophic muscle
      benefits mitochondria and attenuates the downstream pathology associated with
      aberrant mitochondrial function.

PMID- 29065909
TI  - Right drug, right patient, right time: aspiration or future promise for biologics
      in rheumatoid arthritis?
AB  - Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to
      maximise outcomes and deliver safe and cost-effective care is a key goal in the
      management of rheumatoid arthritis (RA). Investigation to identify predictive
      tools of bDMARD response is a highly active and prolific area of research. In
      addition to clinical phenotyping, cellular and molecular characterisation of
      synovial tissue and blood in patients with RA, using different technologies, can
      facilitate predictive testing. This narrative review will summarise the
      literature for the available bDMARD classes and focus on where progress has been
      made. We will also look ahead and consider the increasing use of 'omics'
      technologies, the potential they hold as well as the challenges, and what is
      needed in the future to fully realise our ambition of personalised bDMARD
      treatment.

PMID- 29065912
TI  - Correction to: a comparison of physician emigration from Africa to the United
      States of America between 2005 and 2015.

PMID- 29065911
TI  - Effectiveness of behavioral change techniques employed in eHealth interventions
      designed to improve glycemic control in persons with poorly controlled type 2
      diabetes: a systematic review and meta-analysis protocol.
AB  - BACKGROUND: The incorporation of Behavioral Change Techniques (BCTs) in eHealth
      interventions for the management of non-communicable diseases (NCDs), such as
      type 2 diabetes mellitus (T2DM), might be a promising approach to improve
      clinical and behavioral outcomes of NCDs in the long run. This 3paper reports a
      protocol for a systematic review that aims to (a) identify the effects of
      individual BCTs in eHealth interventions for lowering glycated hemoglobin levels
      (HbA1c) and (b) investigate which additional intervention features (duration of
      intervention, tailoring, theory-base, and mode of delivery) affect levels of
      HbA1c in this population. The protocol follows the Preferred Reporting Items for
      Systematic review and Meta-Analysis Protocols (PRISMA-P) 2015 guideline.
      METHODS/DESIGN: To identify eligible studies, an extensive systematic database
      search (PubMed, Web of Science, and PsycINFO) using keywords will be conducted.
      This review will include randomized controlled trials examining the effects of
      eHealth interventions on HbA1c in persons with poorly controlled T2DM over a
      minimum follow-up period of 3 months. Relevant data will be extracted from the
      included studies using Microsoft Excel. The content of the interventions will be
      extracted from the description of interventions and will be classified according
      to the BCT taxonomy v1 tool. The quality of studies will be independently
      assessed by two reviewers using the Cochrane risk of bias tool. If the studies
      have adequate homogeneity, meta-analysis will be considered. The effect sizes of
      each BCT will be calculated using the random effect model. The quality of the
      synthesized evidence will be evaluated employing the Grading of the
      Recommendations Assessment, Development and Evaluation (GRADE) criteria.
      DISCUSSION: This systematic review is one of the firsts to appraise the
      effectiveness of eHealth interventions employing BCTs which aimed at improving
      glycemic control in persons with poorly controlled T2DM. The review will
      aggregate the effect sizes of BCTs on HbA1c levels. The results may inform future
      eHealth interventions targeting poorly controlled T2DM populations. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42016049940.

PMID- 29065910
TI  - Very high carriage of gametocytes in asymptomatic low-density Plasmodium
      falciparum and P. vivax infections in western Thailand.
AB  - BACKGROUND: Low-density asymptomatic infections of Plasmodium spp. are common in
      low endemicity areas worldwide, but outside Africa, their contribution to malaria
      transmission is poorly understood. Community-based studies with highly sensitive
      molecular diagnostics are needed to quantify the asymptomatic reservoir of
      Plasmodium falciparum and P. vivax infections in Thai communities. METHODS: A
      cross-sectional survey of 4309 participants was conducted in three endemic areas
      in Kanchanaburi and Ratchaburi provinces of Thailand in 2012. The presence of P.
      falciparum and P. vivax parasites was determined using 18S rRNA qPCR. Gametocytes
      were also detected by pfs25 / pvs25 qRT-PCRs. RESULTS: A total of 133 individuals
      were found infected with P. vivax (3.09%), 37 with P. falciparum (0.86%), and 11
      with mixed P. vivax/ P. falciparum (0.26%). The clear majority of both P. vivax
      (91.7%) and P. falciparum (89.8%) infections were not accompanied by any febrile
      symptoms. Infections with either species were most common in adolescent and adult
      males. Recent travel to Myanmar was highly associated with P. falciparum (OR =
      9.0, P = 0.001) but not P. vivax infections (P = 0.13). A large number of P.
      vivax (71.5%) and P. falciparum (72.0%) infections were gametocyte positive by
      pvs25/pfs25 qRT-PCR. Detection of gametocyte-specific pvs25 and pfs25 transcripts
      was strongly dependent on parasite density. pvs25 transcript numbers, a measure
      of gametocyte density, were also highly correlated with parasite density (r 2 =
      0.82, P < 0.001). CONCLUSIONS: Asymptomatic infections with Plasmodium spp. were
      common in western Thai communities in 2012. The high prevalence of gametocytes
      indicates that these infections may contribute substantially to the maintenance
      of local malaria transmission.

PMID- 29065913
TI  - Urine S100 proteins as potential biomarkers of lupus nephritis activity.
AB  - BACKGROUND: Improved, noninvasive biomarkers are needed to accurately detect
      lupus nephritis (LN) activity. The purpose of this study was to evaluate five
      S100 proteins (S100A4, S100A6, S100A8/9, and S100A12) in both serum and urine as
      potential biomarkers of global and renal system-specific disease activity in
      childhood-onset systemic lupus erythematosus (cSLE). METHODS: In this multicenter
      study, S100 proteins were measured in the serum and urine of four cSLE cohorts
      and healthy control subjects using commercial enzyme-linked immunosorbent assays.
      Patients were divided into cohorts on the basis of biospecimen availability: (1)
      longitudinal serum, (2) longitudinal urine, (3) cross-sectional serum, and (4)
      cross-sectional urine. Global and renal disease activity were defined using the
      Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the
      SLEDAI-2K renal domain score. Nonparametric testing was used for statistical
      analysis, including the Wilcoxon signed-rank test, Kruskal-Wallis test, Mann
      Whitney U test, and Spearman's rank correlation coefficient. RESULTS: All urine
      S100 proteins were elevated in patients with active LN compared with patients
      with active extrarenal disease and healthy control subjects. All urine S100
      protein levels decreased with LN improvement, with S100A4 demonstrating the most
      significant decrease. Urine S100A4 levels were also higher with proliferative LN
      than with membranous LN. S100A4 staining in the kidney localized to mononuclear
      cells, podocytes, and distal tubular epithelial cells. Regardless of the S100
      protein tested, serum levels did not change with cSLE improvement. CONCLUSIONS:
      Higher urine S100 levels are associated with increased LN activity in cSLE,
      whereas serum S100 levels do not correlate with disease activity. Urine S100A4
      shows the most promise as an LN activity biomarker, given its pronounced decrease
      with LN improvement, isolated elevation in urine, and positive staining in
      resident renal cells.

PMID- 29065914
TI  - Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern
      China.
AB  - BACKGROUND: There is accumulating evidence for an increased susceptibility to
      infection in patients with arthritis. We sought to understand the epidemiology of
      Toxoplasma gondii infection in arthritis patients in eastern China, given the
      paucity of data on the magnitude of T. gondii infection in these patients.
      METHODS: Seroprevalence of T. gondii infection was assessed by enzyme-linked
      immunosorbent assay using a crude antigen of the parasite in 820 arthritic
      patients, and an equal number of healthy controls, from Qingdao and Weihai
      cities, eastern China. Sociodemographic, clinical and lifestyle information on
      the study participants were also obtained. RESULTS: The prevalence of anti-T.
      gondii IgG was significantly higher in arthritic patients (18.8%) compared with
      12% in healthy controls (P < 0.001). Twelve patients with arthritis had anti-T.
      gondii IgM antibodies - comparable with 10 control patients (1.5% vs 1.2%).
      Demographic factors did not significantly influence these seroprevalence
      frequencies. The highest T. gondii infection seropositivity rate was detected in
      patients with rheumatoid arthritis (24.8%), followed by reactive arthritis
      (23.8%), osteoarthritis (19%), infectious arthritis (18.4%) and gouty arthritis
      (14.8%). Seroprevalence rates of rheumatoid arthritis and reactive arthritis were
      significantly higher when compared with controls (P < 0.001 and P = 0.002,
      respectively). A significant association was detected between T. gondii infection
      and cats being present in the home in arthritic patients (odds ratio [OR], 1.68;
      95% confidence interval [CI]: 1.24 - 2.28; P = 0.001). CONCLUSIONS: These
      findings are consistent with and extend previous results, providing further
      evidence to support a link between contact with cats and an increased risk of T.
      gondii infection. Our study is also the first to confirm an association between
      T. gondii infection and arthritis patients in China. Implications for better
      prevention and control of T. gondii infection in arthritis patients are
      discussed. TRIAL REGISTRATION: This is an epidemiological survey, therefore trial
      registration was not required.

PMID- 29065915
TI  - Interventions for acute stroke management in Africa: a systematic review of the
      evidence.
AB  - BACKGROUND: The past decades have witnessed a rapid evolution of research on
      evidence-based acute stroke care interventions worldwide. Nonetheless, the
      evidence-to-practice gap in acute stroke care remains variable with slow and
      inconsistent uptake in low-middle income countries (LMICs). This review aims to
      identify and compare evidence-based acute stroke management interventions with
      alternative care on overall patient mortality and morbidity outcomes, functional
      independence, and length of hospital stay across Africa. METHODS: This review was
      conducted according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) guideline. An electronic search was conducted in six
      databases comprising MEDLINE, Embase, Cumulative Index to Nursing and Allied
      Health Literature (CINAHL), Web of Science, Academic Search Complete and Cochrane
      Library for experimental and non-experimental studies. Eligible studies were
      abstracted into evidence tables and their methodological quality appraised using
      the Joanna Briggs Institute checklist. Data were analysed and presented
      narratively with reference to observed differences in patient outcomes, reporting
      p values and confidence intervals for any possible relationship. RESULTS:
      Initially, 1896 articles were identified and 37 fully screened. Four non
      experimental studies (three cohort and one case series studies) were included in
      the final review. One study focused on the clinical efficacy of a stroke unit
      whilst the remaining three reported on thrombolytic therapy. The results
      demonstrated a reduction in patient deaths attributed to stroke unit care and
      thrombolytic therapy. Thrombolytic therapy was also associated with reductions in
      symptomatic intracerebral haemorrhage (SICH). However, the limited eligible
      studies and methodological limitations compromised definitive conclusions on the
      extent of and level of efficacy of evidence-based acute stroke care interventions
      across Africa. CONCLUSION: Evidence from this review confirms the widespread
      assertion of low applicability and uptake of evidence-based acute stroke care in
      LMICs. Despite the limited eligible studies, the overall positive patient
      outcomes following such interventions demonstrate the applicability and value of
      evidence-based acute stroke care interventions in Africa. Health policy attention
      is thus required to ensure widespread applicability of such interventions for
      improved patients' outcomes. The review findings also emphasises the need for
      further research to unravel the reasons for low uptake. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42016051566.

PMID- 29065917
TI  - Is it them or is it us? Unravelling ethnic disparities in undergraduate clinical
      performance.
AB  - Given our increasingly diverse societies, there is an urgent need for research
      into the causes of persistent ethnic disparities in undergraduate clinical
      performance. It is argued that causes for underperformance can be identified from
      two perspectives, namely that of the students ('them') and that of the academic
      environment ('us'). Taking the 'us' perspective, Yeates et al. conducted a
      detailed experimental study aimed at understanding the processes underlying
      judgment and decision-making in clinical assessments. Contrary to their
      expectations, their study indicates that, despite the presence of active
      stereotypes, examiner bias does not explain ethnic minority students'
      underperformance. Naturally, future studies are required to confirm their
      findings. It is suggested that these studies should take into account various
      rater and situational factors (e.g. rater experience, increased cognitive load)
      that may influence examiners' reliance on stereotypes. However, future work
      should also focus on other potential impeding factors from both perspectives,
      including differences in communication styles. Knowing what leads to the ethnic
      disparities in performance is a prerequisite for designing interventions aimed at
      ensuring a level playing field for a diverse student population.Please see
      related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916
      017-0943-0.

PMID- 29065916
TI  - A randomised controlled trial assessing the severity and duration of depressive
      symptoms associated with a clinically significant response to sertraline versus
      placebo, in people presenting to primary care with depression (PANDA trial):
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: Depressive symptoms are usually managed within primary care and
      antidepressant medication constitutes the first-line treatment. It remains
      unclear at present which people are more likely to benefit from antidepressant
      medication. This paper describes the protocol for a randomised controlled trial
      (PANDA) to investigate the severity and duration of depressive symptoms that are
      associated with a clinically significant response to sertraline compared to
      placebo, in people presenting to primary care with depression. METHODS/DESIGN:
      PANDA is a randomised, double blind, placebo controlled trial in which
      participants are individually randomised to sertraline or placebo. Eligible
      participants are those who are between the ages of 18 to 74; have presented to
      primary care with depression or low mood during the past 2 years; have not
      received antidepressant or anti-anxiety medication in the 8 weeks prior to
      enrolment in the trial and there is clinical equipoise about the benefits of
      selective serotonin reuptake inhibitor (SSRI) medication. Participants who
      consent to participate in the trial are randomised to receive either sertraline
      or matching placebo, starting at 50 mg daily for 1 week, increasing to 100 mg
      daily for up to 11 weeks (with the option of increasing to 150 mg if required).
      Participants, general practitioners (GPs) and the research team will be blind to
      treatment allocation. The primary outcome will be depressive symptoms measured by
      the Patient Health Questionnaire-9 (PHQ-9) at 6 weeks post randomisation,
      measured as a continuous outcome. Secondary outcomes include depressive symptoms
      measured with the PHQ-9 at 2 and 12 weeks as a continuous outcome and at 2, 6 and
      12 weeks as a binary outcome; follow-up scores on depressive symptoms measured
      with the Beck Depression Inventory-II, anxiety symptoms measured by the
      Generalized Anxiety Disorder-7 and quality of life measured with the Euroqol-5D
      5L and Short Form-12; emotional processing task scores measured at baseline, 2
      and 6 weeks; and costs associated with healthcare use, time off work and personal
      costs. DISCUSSION: The PANDA trial uses a simple self-administered measure to
      establish the severity and duration of depressive symptoms associated with a
      clinically significant response to sertraline. The evidence from the trial will
      inform primary care prescribing practice by identifying which patients are more
      likely to benefit from antidepressants. TRIAL REGISTRATION: Controlled Trials
      ISRCTN Registry, ISRCTN84544741 . Registered on 20 March 2014. EudraCT Number:
      2013-003440-22; Protocol Number: 13/0413 (version 6.1).

PMID- 29065918
TI  - Sex differences in drugs: the development of a comprehensive knowledge base to
      improve gender awareness prescribing.

PMID- 29065919
TI  - Diabetes-related information-seeking behaviour: a systematic review.
AB  - BACKGROUND: Information-seeking behaviour is necessary to improve knowledge on
      diabetes therapy and complications. Combined with other self-management skills
      and autonomous handling of the disease, it is essential for achieving treatment
      targets. However, a systematic review addressing this topic is lacking. The aims
      of this systematic review were to identify and analyse existing knowledge of
      information-seeking behaviour: (1) types information-seeking behaviour, (2)
      information sources, (3) the content of searched information, and (4) associated
      variables that may affect information-seeking behaviour. METHODS: The systematic
      review follows the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) requirements. MEDLINE, CINAHL, EMBASE, ScienceDirect, PsycInfo,
      Cochrane Library, Web of Science, CCMed, ERIC, Journals@OVID, Deutsches
      Arzteblatt and Karlsruher virtueller Katalog (KvK) databases were searched.
      Publications dealing with information-seeking behaviour of people with diabetes
      mellitus published up to June 2015 were included. A forward citation tracking was
      performed in September 2016 and June 2017. Additionally, an update of the two
      main databases (MEDLINE, CINAHL) was conducted, considering studies published up
      to July 2017. Studies published in languages other than English or German were
      excluded, as well as letters, short reports, editorials, comments and discussion
      papers. A study selection and the critical appraisal of the selected studies were
      performed independently by two reviewers. A third reviewer was consulted if any
      disagreement was found. Data extraction and content analysis were performed using
      selected dimensions of Wilson's 'model of information behaviour'. RESULTS: Twenty
      six studies were included. Five 'types of information-seeking behaviour' were
      identified, e.g. passive and active search. The 'Internet' and 'healthcare
      professionals' were the most frequently reported sources. 'Diet',
      'complications', 'exercise' and 'medications and pharmacological interactions'
      were the most frequently identified content of information. Seven main categories
      including associated variables were identified, e.g. 'socioeconomic', 'duration
      of DM', and 'lifestyle'. CONCLUSION: The systematic review provides a valuable
      overview of available knowledge on the information-seeking behaviour of people
      with diabetes mellitus, although there are only a few studies. There was a high
      heterogeneity regarding the research question, design, methods and participants.
      Although the Internet is often used to seek information, health professionals
      still play an important role in supporting their patients' information-seeking
      behaviour. Specific needs of people with diabetes must be taken into
      consideration. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037312.

PMID- 29065920
TI  - Addition of T2-guided optical tomography improves noncontrast breast magnetic
      resonance imaging diagnosis.
AB  - BACKGROUND: While dynamic contrast-enhanced magnetic resonance imaging (DCE MRI)
      is recognized as the most sensitive examination for breast cancer detection, it
      has a substantial false positive rate and gadolinium (Gd) contrast agents are not
      universally well tolerated. As a result, alternatives to diagnosing breast cancer
      based on endogenous contrast are of growing interest. In this study, endogenous
      near-infrared spectral tomography (NIRST) guided by T2 MRI was evaluated to
      explore whether the combined imaging modality, which does not require contrast
      injection or involve ionizing radiation, can achieve acceptable diagnostic
      performance. METHODS: Twenty-four subjects-16 with pathologically confirmed
      malignancy and 8 with benign abnormalities-were simultaneously imaged with MRI
      and NIRST prior to definitive pathological diagnosis. MRIs were evaluated
      independently by three breast radiologists blinded to the pathological results.
      Optical image reconstructions were constrained by grayscale values in the T2 MRI.
      MRI and NIRST images were used, alone and in combination, to estimate the
      diagnostic performance of the data. Outcomes were compared to DCE results.
      RESULTS: Sensitivity, specificity, accuracy, and area under the curve (AUC) of
      noncontrast MRI when combined with T2-guided NIRST were 94%, 100%, 96%, and 0.95,
      respectively, whereas these values were 94%, 63%, 88%, and 0.81 for DCE MRI
      alone, and 88%, 88%, 88%, and 0.94 when DCE-guided NIRST was added. CONCLUSION:
      In this study, the overall accuracy of imaging diagnosis improved to 96% when T2
      guided NIRST was added to noncontrast MRI alone, relative to 88% for DCE MRI,
      suggesting that similar or better diagnostic accuracy can be achieved without
      requiring a contrast agent.

PMID- 29065921
TI  - Fibroblast bioenergetics to classify amyotrophic lateral sclerosis patients.
AB  - BACKGROUND: The objective of this study was to investigate cellular bioenergetics
      in primary skin fibroblasts derived from patients with amyotrophic lateral
      sclerosis (ALS) and to determine if they can be used as classifiers for patient
      stratification. METHODS: We assembled a collection of unprecedented size of
      fibroblasts from patients with sporadic ALS (sALS, n = 171), primary lateral
      sclerosis (PLS, n = 34), ALS/PLS with C9orf72 mutations (n = 13), and healthy
      controls (n = 91). In search for novel ALS classifiers, we performed extensive
      studies of fibroblast bioenergetics, including mitochondrial membrane potential,
      respiration, glycolysis, and ATP content. Next, we developed a machine learning
      approach to determine whether fibroblast bioenergetic features could be used to
      stratify patients. RESULTS: Compared to controls, sALS and PLS fibroblasts had
      higher average mitochondrial membrane potential, respiration, and glycolysis,
      suggesting that they were in a hypermetabolic state. Only membrane potential was
      elevated in C9Orf72 lines. ATP steady state levels did not correlate with
      respiration and glycolysis in sALS and PLS lines. Based on bioenergetic profiles,
      a support vector machine (SVM) was trained to classify sALS and PLS with 99%
      specificity and 70% sensitivity. CONCLUSIONS: sALS, PLS, and C9Orf72 fibroblasts
      share hypermetabolic features, while presenting differences of bioenergetics. The
      absence of correlation between energy metabolism activation and ATP levels in
      sALS and PLS fibroblasts suggests that in these cells hypermetabolism is a
      mechanism to adapt to energy dissipation. Results from SVM support the use of
      metabolic characteristics of ALS fibroblasts and multivariate analysis to develop
      classifiers for patient stratification.

PMID- 29065922
TI  - Persisting demand and supply gap for maternal and newborn care in eastern Uganda:
      a mixed-method cross-sectional study.
AB  - BACKGROUND: The slow progress in reducing maternal and newborn death in low and
      middle-income countries is attributed to both demand and supply-side factors.
      This study assessed the changes in maternal and newborn services in health
      facilities as well as demand for maternal and newborn health services in Eastern
      Uganda. METHODS: The health assessment data were collected in August 2013 and
      September 2015 in the districts of Kamuli, Pallisa, and Kibuku. We purposively
      collected data on the availability of services from 40 health facilities that
      provided maternal and newborn services. In addition, we conducted 24 focus group
      discussions (FGDs) with women and men; and 18 key informant interviews (KIs) with
      health workers. RESULTS: On the supply side, most health facilities persistently
      lacked lifesaving medicines such as misoprostol, IV Ampicillin, IV Gentamycin, IV
      Metronidazole, Magnesium Sulphate, Ergometrine, Corticosteroids, ferrous
      Sulphate, Folic Acid, Combined ferrous, Benzyl penicillin, and Diazepam (IM or
      IV). Basic newborn equipment such as stethoscope, fetal scope, working baby
      scale, newborn suction devices, newborn resuscitation device, and thermometer
      were persistently not available in most of the health facilities. Binders for
      Kangaroo Mother Care, blanket to wrap newborn, baby warmer or heat lamp were
      persistently not available in at least 80% of the health facilities. Other
      equipment for the management of labor and abortions such as Manual vacuum
      aspirator for abortion care, blank partographs and vacuum extractor were not
      available in most of the health facilities including referral facilities at
      baseline and follow-up. On the demand side, the qualitative interviews exposed
      long distances and inadequate transport to the health facilities, inadequate
      information, poverty, and poor services at the health facilities as major factors
      that impede women to utilize/access maternal and newborn services. CONCLUSION:
      There are distinct influences on both demand and supply side, which restrain both
      health care uptake and its quality. The frequent disparity between the health
      facility readiness to provide services and the women readiness to utilize them
      needs to be addressed as the country intensifies its efforts to reduce maternal
      and newborn deaths through boosting facility deliveries.

PMID- 29065923
TI  - Impact of 6 months of treatment with intragastric balloon on body fat and quality
      of life in obese individuals with metabolic syndrome.
AB  - BACKGROUND: Obesity is a worldwide public health issue with a negative impact on
      quality of life. Different weight loss interventions have demonstrated
      improvements in quality of life. The aim of this study was to investigate the
      effect of 6 months of treatment with an intragastric balloon (IGB) on health
      related quality of life (HRQOL) and its relation to changes in body fat in obese
      individuals with metabolic syndrome (MS). METHODS: Fifty obese patients with MS
      aged 18-50 were selected for treatment with IGB for 6 months. Body fat was
      assessed with anthropometric measures and dual-energy X-ray absorptiometry (DXA)
      at baseline and after removal of the IGB. HRQOL was evaluated with the short form
      of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and
      soon after removal of the IGB. RESULTS: Thirty-nine patients completed the study.
      After 6 months, there was a significant improvement in quality of life (p =
      0.0009) and health (p < 0.0001) perceptions, and in the Physical (p = 0.001),
      Psychological (p = 0.031), and Environmental domains (p = 0.0071). Anthropometric
      measures and total fat determined by DXA were directly and significantly related
      to an improvement in general aspects of quality of life. The decrease in the
      percentage of total fat was the parameter that better correlated with
      improvements in quality of life perception after regression (p = 0.032).
      CONCLUSIONS: In obese individuals with MS, weight loss parameters were associated
      with short-term improvements in HRQOL after 6 months of treatment with IGB.
      However, only total fat was independently related to HRQOL perception. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01598233 .

PMID- 29065924
TI  - Dose-response relationship between lower serum magnesium level and higher
      prevalence of knee chondrocalcinosis.
AB  - BACKGROUND: The aim was to assess serum magnesium levels in relation to
      prevalence of knee chondrocalcinosis in two population-based Chinese studies.
      METHODS: Data included in this analysis consisted of two population-based cross
      sectional studies, i.e., the Xiangya Hospital Health Management Center Study and
      the Xiangya Osteoarthritis (XO) Study I. A bilateral knee anteroposterior
      radiograph was obtained from each subject. Radiographic knee chondrocalcinosis
      was present if there was definite linear cartilage calcification. Serum magnesium
      concentration was measured using the chemiluminescence method. We examined the
      relation of serum magnesium levels to prevalence of knee chondrocalcinosis using
      generalized estimating equations. RESULTS: The prevalence of knee
      chondrocalcinosis was 1.4% in the Xiangya Hospital Health Management Center Study
      (n = 12,631). Compared with the lowest tertile, the age, sex and body mass index
      (BMI)-adjusted odds ratios (ORs) of chondrocalcinosis were 0.59 (95% CI 0.40
      0.87) and 0.49 (95% CI 0.33-0.72) in the second and the third tertiles of serum
      magnesium, respectively (P for trend <0.001). The prevalence of knee
      chondrocalcinosis in the XO Study I (n = 1316) was 4.1%. The age, sex and BMI
      adjusted ORs of chondrocalcinosis were 0.67 (95% CI 0.34-1.30) in the second and
      0.45 (95% CI 0.21-0.94) in the third tertile of serum magnesium when compared
      with the lowest tertile (P for trend = 0.030). Similar results were observed in
      men and women in both studies. Adjusting for additional potential confounders did
      not change the results materially. CONCLUSIONS: Subjects with lower levels of
      serum magnesium, even within the normal range, had higher prevalence of knee
      chondrocalcinosis in a dose-response relationship manner, suggesting that
      magnesium may have a preventive or therapeutic potential for knee
      chondrocalcinosis.

PMID- 29065925
TI  - Ultrasound verified inflammation and structural damage in patients with
      hereditary haemochromatosis-related arthropathy.
AB  - BACKGROUND: Chronic arthropathy occurs in approximately two thirds of patients
      with hereditary haemochromatosis (HH). The aim was to study inflammatory and
      structural lesions in patients with HH with (HH-A) and without arthropathy (HH
      WA) using ultrasonography. METHODS: This was a cross-sectional study of 26
      patients with HH-A, 24 with HH-WA and 37 with hand osteoarthritis (HOA). Clinical
      examination was performed in 68 joints, and we retrieved data on hand function,
      pain and global disease activity (all using a visual analogue scale (VAS)),
      morning stiffness and ferritin levels. Standard x-ray and ultrasound were
      conducted in 36 joints (hands, hips, knees and ankles), and we graded grey scale
      synovitis (GSS), power Doppler ultrasound (PD), osteophytes, erosions,
      tenosynovitis and cartilage damage semi-quantitatively in accordance with prior
      publications. RESULTS: Ultrasound revealed a high proportion of inflammatory
      changes in HH-A; GSS was found in 96.2% and PD signals in 80.8% of patients
      (median GSS score 9, PD score 2.5). The frequency of these findings was similar
      in HOA. Inflammation was also common in HH-WA, yielding GSS in 83.3% and PD
      signals in 50.0% of patients. Cartilage damage was most prominent in HH-A as
      compared to HH-WA and HOA (median scores 11.0, 2.5 and 2.0, respectively). The
      prevalence and extent of erosions and osteophytes were similar in all groups.
      None of the ultrasound scores was associated with pain or function; GSS, PD,
      osteophyte and cartilage scores correlated with x-ray-verified structural damage.
      CONCLUSION: A high prevalence of ultrasound-verified inflammation and cartilage
      damage was found in HH-A, and to a lesser extent in HH-WA. These findings were
      associated with x-ray-verified damage but not with clinical scores of pain and
      function.

PMID- 29065926
TI  - Glucagon-like peptide receptor agonists attenuate advanced glycation end products
      induced inflammation in rat mesangial cells.
AB  - BACKGROUND: Hyperglycemia-induced advanced glycation end products (AGEs) and
      receptor for AGEs (RAGE) production play major roles in progression of diabetic
      nephropathy. Anti-RAGE effect of peroxisome proliferator-activated receptor-delta
      (PPARdelta) agonists was shown in previous studies. PPARdelta agonists also
      stimulate glucagon-like peptide-1 (GLP-1) secretion from human intestinal cells.
      METHODS: In this study, the individual and synergic anti-inflammatory effects of
      GLP-1 receptor (exendin-4) and PPARdelta (L-165,041) agonists in AGE-treated rat
      mesangial cells (RMC) were investigated. RESULTS: The results showed both exendin
      4 and L-165,041 significantly attenuated AGE-induced IL-6 and TNF-alpha
      production, RAGE expression, and cell death in RMC. Similar anti-inflammatory
      potency was seen between 0.3 nM exendin-4 and 1 MUM L-165,041. Synergic effect of
      exendin-4 and L-165,041 was shown in inhibiting cytokines production, but not in
      inhibiting RAGE expression or cell death. CONCLUSIONS: These results suggest that
      both GLP-1 receptor and PPARdelta agonists have anti-inflammatory effect on AGE
      treated rat mesangial cells.

PMID- 29065927
TI  - The protective role of estrogen and estrogen receptors in cardiovascular disease
      and the controversial use of estrogen therapy.
AB  - Epidemiologic studies have previously suggested that premenopausal females have
      reduced incidence of cardiovascular disease (CVD) when compared to age-matched
      males, and the incidence and severity of CVD increases postmenopause. The lower
      incidence of cardiovascular disease in women during reproductive age is
      attributed at least in part to estrogen (E2). E2 binds to the traditional E2
      receptors (ERs), estrogen receptor alpha (ERalpha), and estrogen receptor beta
      (ERbeta), as well as the more recently identified G-protein-coupled ER (GPR30),
      and can exert both genomic and non-genomic actions. This review summarizes the
      protective role of E2 and its receptors in the cardiovascular system and
      discusses its underlying mechanisms with an emphasis on oxidative stress,
      fibrosis, angiogenesis, and vascular function. This review also presents the
      sexual dimorphic role of ERs in modulating E2 action in cardiovascular disease.
      The controversies surrounding the clinical use of exogenous E2 as a therapeutic
      agent for cardiovascular disease in women due to the possible risks of thrombotic
      events, cancers, and arrhythmia are also discussed. Endogenous local E2
      biosynthesis from the conversion of testosterone to E2 via aromatase enzyme
      offers a novel therapeutic paradigm. Targeting specific ERs in the cardiovascular
      system may result in novel and possibly safer therapeutic options for
      cardiovascular protection.

PMID- 29065929
TI  - VEGF promotes endothelial progenitor cell differentiation and vascular repair
      through connexin 43.
AB  - BACKGROUND: Endothelial progenitor cell (EPC) differentiation is considered
      crucial for vascular repair. Vascular endothelial growth factor (VEGF) induces
      EPC differentiation, but the underlying mechanism of this phenomenon remains
      unclear. Connexin 43 (Cx43) is reported to be involved in the regulation of stem
      cell differentiation. Therefore, we sought to determine whether Cx43 is involved
      in VEGF-induced EPC differentiation and vascular repair. METHODS: Rat spleen
      derived EPCs were cultured and treated with various concentrations of VEGF (0,
      10, or 50 ng/mL), and the relationship between EPC differentiation and Cx43
      expression was evaluated. Thereafter, fluorescence redistribution after
      photobleaching was performed to assess the relationship between adjacent EPC
      differentiation and Cx43-induced gap junction intercellular communication (GJIC).
      After carotid artery injury, EPCs pretreated with VEGF were injected into the
      tail veins, and the effects of Cx43 on vascular repair were evaluated. RESULTS:
      EPCs cultured with VEGF exhibited accelerated differentiation and increased
      expression of Cx43. However, inhibition of Cx43 expression using short
      interfering RNA (siRNA) attenuated EPC GJIC and consequent EPC differentiation.
      VEGF-pretreated EPC transplantation promoted EPC homing and reendothelialization,
      and inhibited neointimal formation. These effects were attenuated by siRNA
      inhibition of Cx43. CONCLUSIONS: Our results from in vivo and in vitro
      experiments indicated that VEGF promotes EPC differentiation and vascular repair
      through Cx43.

PMID- 29065932
TI  - Sleep and dietary habits in the urban environment: the role of chrono-nutrition.
AB  - The urban environment has changed vastly over past decades, which also has had an
      impact on our sleep and dietary patterns and possibly health outcomes. Some
      studies have shown that sleep duration and sleep quality has declined over past
      decades, especially in children. In parallel, our lifestyle and dietary patterns
      have also changed including more shift work, more meals outside the home or
      family setting and more irregular eating patterns, including breakfast skipping
      and late-night eating. This new area of research in nutritional sciences studying
      the impact of the timing of eating on health outcomes is called chrono-nutrition,
      and combines elements from nutritional research with chrono-biology. The
      objectives of this paper were to discuss secular trends in sleep patterns and
      related dietary patterns, introduce basic concepts and mechanisms of chrono
      nutrition and discuss the evidence for the importance of sleep and chrono
      nutrition in relation to health outcomes. Overall, chrono-nutrition could mediate
      the effects between sleep, diet and urbanisation, and more research is needed to
      elucidate the importance of chrono-nutrition for metabolic health and its impact
      on public health.

PMID- 29065928
TI  - Chromatin status and transcription factor binding to gonadotropin promoters in
      gonadotrope cell lines.
AB  - BACKGROUND: Proper expression of key reproductive hormones from gonadotrope cells
      of the pituitary is required for pubertal onset and reproduction. To further our
      understanding of the molecular events taking place during embryonic development,
      leading to expression of the glycoproteins luteinizing hormone (LH) and follicle
      stimulating hormone (FSH), we characterized chromatin structure changes, imparted
      mainly by histone modifications, in model gonadotrope cell lines. METHODS: We
      evaluated chromatin status and gene expression profiles by chromatin
      immunoprecipitation assays, DNase sensitivity assay, and RNA sequencing in three
      developmentally staged gonadotrope cell lines, alphaT1-1 (progenitor, expressing
      Cga), alphaT3-1 (immature, expressing Cga and Gnrhr), and LbetaT2 (mature,
      expressing Cga, Gnrhr, Lhb, and Fshb), to assess changes in chromatin status and
      transcription factor access of gonadotrope-specific genes. RESULTS: We found the
      common mRNA alpha-subunit of LH and FSH, called Cga, to have an open chromatin
      conformation in all three cell lines. In contrast, chromatin status of Gnrhr is
      open only in alphaT3-1 and LbetaT2 cells. Lhb begins to open in LbetaT2 cells and
      was further opened by activin treatment. Histone H3 modifications associated with
      active chromatin were high on Gnrhr in alphaT3-1 and LbetaT2, and Lhb in LbetaT2
      cells, while H3 modifications associated with repressed chromatin were low on
      Gnrhr, Lhb, and Fshb in LbetaT2 cells. Finally, chromatin status correlates with
      the progressive access of LHX3 to Cga and Gnrhr, followed by PITX1 binding to the
      Lhb promoter. CONCLUSION: Our data show the gonadotrope-specific genes Cga,
      Gnrhr, Lhb, and Fshb are not only controlled by developmental transcription
      factors, but also by epigenetic mechanisms that include the modulation of
      chromatin structure, and histone modifications.

PMID- 29065930
TI  - Optimization and characterization of spray-dried IgG formulations: a design of
      experiment approach.
AB  - BACKGROUND: The purpose of the present study is to optimize a spray-dried
      formulation as a model antibody regarding stability and aerodynamic property for
      further aerosol therapy of this group of macromolecules. METHOD: A three-factor,
      three-level, Box-Behnken design was employed milligrams of Cysteine (X1),
      Trehalose (X2), and Tween 20 (X3) as independent variables. The dependent
      variables were quantified and the optimized formulation was prepared accordingly.
      SEC-HPLC and FTIR-spectroscopy were conducted to evaluate the molecular and
      structural status of spray-dried preparations. Particle characterization of
      optimized sample was performed with the aid of DSC, SEM, and TSI examinations.
      RESULTS: Experimental responses of a total of 17 formulations resulted in yield
      values, (Y1), ranging from 21.1 +/- 0.2 to 40.2 +/- 0.1 (%); beta-sheet content,
      (Y2), from 66.22 +/- 0.19 to 73.78 +/- 0.26 (%); amount of aggregation following
      process, (Y3), ranging from 0.11 +/- 0.03 to 0.95 +/- 0.03 (%); and amount of
      aggregation upon storage, (Y4), from 0.81 +/- 0.01 to 3.13 +/- 0.64 (%) as
      dependent variables. Results-except for those of the beta sheet content-were
      fitted to quadratic models describing the inherent relationship between main
      factors. CONCLUSION: Co-application of Cysteine and Tween 20 preserved antibody
      molecules from molecular degradation and improved immediate and accelerated
      stability of spry-dried antibodies. Validation of the optimization study
      indicated high degree of prognostic ability of response surface methodology in
      preparation of stable spray-dried IgG. Graphical abstract Spray drying of IgG in
      the presence of Trehalose, Cysteine and Tween 20.

PMID- 29065931
TI  - Relevance of structural damage in the sacroiliac joints for the functional status
      and spinal mobility in patients with axial spondyloarthritis: results from the
      German Spondyloarthritis Inception Cohort.
AB  - BACKGROUND: Functional status and spinal mobility in patients with axial
      spondyloarthritis (axSpA) are known to be determined both by disease activity and
      by structural damage in the spine. The impact of structural damage in the
      sacroiliac joints (SIJ) on physical function and spinal mobility in axSpA has not
      been studied so far. The objective of the study was to analyze the impact of
      radiographic sacroiliitis on functional status and spinal mobility in patients
      with axSpA. METHODS: In total, 210 patients with axSpA were included in the
      analysis. Radiographs of SIJ obtained at baseline and after 2 years of follow up
      were scored by two trained readers according to the modified New York criteria
      grading system (grade 0-4). The mean of two readers' scores for each joint and a
      sum score for both SIJ were calculated for each patient giving a sacroiliitis sum
      score between 0 and 8. The Bath Ankylosing Spondylitis Functional Index (BASFI)
      and Bath Ankylosing Spondylitis Metrology Index (BASMI) at baseline and after 2
      years were used as outcome measures. RESULTS: Longitudinal mixed model analysis
      adjusted for structural damage in the spine (modified Stoke Ankylosing
      Spondylitis Spine Score - mSASSS), disease activity (Bath Ankylosing Spondylitis
      Disease Activity Index - BASDAI and C-reactive protein level) and gender,
      revealed an independent association of the sacroiliitis sum score with the BASFI:
      b = 0.10 (95% CI 0.01-0.19) and the BASMI: b = 0.12 (95% CI 0.03-0.21),
      respectively, indicating that change by one radiographic sacroiliitis grade in
      one joint is associated with BASFI/BASMI worsening by 0.10/0.12 points,
      respectively, independently of disease activity and structural damage in the
      spine. CONCLUSION: Structural damage in the SIJ might have an impact on
      functional status and spinal mobility in axSpA independently of spinal structural
      damage and disease activity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01277419
      . Registered on 14 January 2011.

PMID- 29065933
TI  - MAKING REPLICATION MAINSTREAM.
AB  - Many philosophers of science and methodologists have argued that the ability to
      repeat studies and obtain similar results is an essential component of science. A
      finding is elevated from single observation to scientific evidence when the
      procedures that were used to obtain it can be reproduced and the finding itself
      can be replicated. Recent replication attempts show that some high profile
      results---most notably in psychology, but in many other disciplines as well--
      cannot be replicated consistently. These replication attempts have generated a
      considerable amount of controversy and the issue of whether direct replications
      have value has, in particular, proven to be contentious. However, much of this
      discussion has occurred in published commentaries and social media outlets,
      resulting in a fragmented discourse. To address the need for an integrative
      summary, we review various types of replication studies and then discuss the most
      commonly voiced concerns about direct replication. We provide detailed responses
      to these concerns and consider different statistical ways to evaluate
      replications. We conclude there are no theoretical or statistical obstacles to
      making direct replication a routine aspect of psychological science.

PMID- 29065934
TI  - Polygenic risk for schizophrenia, transition and cortical gyrification: a high
      risk study.
AB  - BACKGROUND: Schizophrenia is a highly heritable disorder, linked to several
      structural abnormalities of the brain. More specifically, previous findings have
      suggested that increased gyrification in frontal and temporal regions are
      implicated in the pathogenesis of schizophrenia. METHODS: The current study
      included participants at high familial risk of schizophrenia who remained well (n
      = 31), who developed sub-diagnostic symptoms (n = 28) and who developed
      schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested
      whether individuals at high familial risk of schizophrenia carried an increased
      burden of trait-associated alleles using polygenic risk score analysis. We then
      assessed the extent to which polygenic risk was associated with gyral folding in
      the frontal and temporal lobes. RESULTS: We found that individuals at high
      familial risk of schizophrenia who developed schizophrenia carried a
      significantly greater burden of risk-conferring variants for the disorder
      compared to those at high risk (HR) who developed sub-diagnostic symptoms or
      remained well and HC. Furthermore, within the HR cohort, there was a significant
      and positive association between schizophrenia polygenic risk score and bilateral
      frontal gyrification. CONCLUSIONS: These results suggest that polygenic risk for
      schizophrenia impacts upon early neurodevelopment to confer greater gyral folding
      in adulthood and an increased risk of developing the disorder.

PMID- 29065936
TI  - John Dalton and the origin of the atomic theory: reassessing the influence of
      Bryan Higgins.
AB  - During the years 1814-1819, William Higgins, an Irish chemist who worked at the
      Dublin Society, claimed he had anticipated John Dalton in developing the atomic
      theory and insinuated that Dalton was a plagiarist. This essay focuses not on
      William Higgins, but on his uncle Bryan Higgins, a well-known chemist of his day,
      who had developed his own theories of caloric and chemical combination, similar
      in many respects to that of Dalton. New evidence is first introduced addressing
      Bryan's disappearance from the scientific community after 1803. In his later
      years, Bryan apparently suffered from a condition resulting in a decline in his
      mental health, which explains why he never lodged any priority claims of his own
      against Dalton, or defended those of his nephew. Dalton's mention of Bryan's name
      in Part II of A New System of Chemical Philosophy, his laboratory notebook
      entries, and a fresh look at his correspondence with chemist Thomas Charles Hope
      indicate that Dalton adopted a Higgins-like caloric model in 1803. Together these
      factors provide evidence to support the argument that Dalton learned of Bryan's
      theories via a meeting he had with William Allen on 10 July 1803. Existing
      evidence related to the origin of the atomic theory is worthy of re-examination
      in light of Dalton's possible prior knowledge of Bryan's work.

PMID- 29065935
TI  - Declines in prevalence of adolescent substance use disorders and delinquent
      behaviors in the USA: a unitary trend?
AB  - BACKGROUND: Downward trends in a number of adolescent risk behaviors including
      violence, crime, and drug use have been observed in the USA in recent years. It
      is unknown whether these are separate trends or whether they might relate to a
      general reduction in propensity to engage in such behaviors. Our objectives were
      to quantify trends in substance use disorders (SUDs) and delinquent behaviors
      over the 2003-2014 period and to determine whether they might reflect a single
      trend in an Externalizing-like trait. METHODS: We analyzed data from 12 to 17
      year old participants from the National Survey on Drug Use and Health, a
      representative survey of the household dwelling population of the USA, across the
      2003-2014 period (N = 210 599). Outcomes included past-year prevalence of six
      categories of substance use disorder and six categories of delinquent behavior.
      RESULTS: Trend analysis suggested a net decline of 49% in mean number of SUDs and
      a 34% decline in delinquent behaviors over the 12-year period. Item Response
      Theory models were consistent with the interpretation that declines in each set
      of outcomes could be attributed to changes in mean levels of a latent,
      Externalizing-like trait. CONCLUSIONS: Our findings suggest that declines in SUDs
      and some delinquent behaviors reflect a single trend related to an Externalizing
      like trait. Identifying the factors contributing to this trend may facilitate
      continued improvement across a spectrum of adolescent risk behaviors.

PMID- 29065937
TI  - EXPLORATION AND PREFERENTIAL RANKING OF PATIENT BENEFITS OF MEDICAL DEVICES: A
      NEW AND GENERIC INSTRUMENT FOR HEALTH ECONOMIC ASSESSMENTS.
AB  - OBJECTIVES: For medical devices, benefits other than direct clinical effects may
      have a large impact on the patients' well-being, but a standardized method for
      measuring these benefits is unavailable. The objective was to explore potential
      patient benefits provided by medical devices, and to assess the relative
      preferences of these benefits in the general Swedish population. METHODS: To
      identify attributes of patient benefit, healthcare personnel within a wide range
      of disease areas were interviewed. The generalized attributes were then validated
      among healthcare personnel, patient organizations, and manufacturers; in two
      pilot studies in the general population; and in two rounds of cognitive
      interviews. The general population's preferences of the attributes were measured
      with a usability-tested questionnaire in a final responding sample of 3,802
      individuals, representative of the Swedish population. RESULTS: Twenty attributes
      were identified, encompassing aspects of integrity, sense of security, social
      participation, and convenience. When measuring the relative preferences, the
      response rate was 37.0 percent, and the results showed that the attributes with
      the highest preferences concerned reliability, reduced need for assistance, and
      sense of control of the illness/disability. CONCLUSIONS: A set of twenty
      attributes of patient benefit relevant to users of medical devices was identified
      and validated. A questionnaire for patient-reported assessment of the benefits
      provided by a medical device was developed, based on the attributes. The
      questionnaire, designated MedTech20, provides a generic measurement method for
      the evaluation of medical devices used in a wide range of diseases/disabilities.

PMID- 29065938
TI  - Review: Pork production with maximal nitrogen efficiency.
AB  - During growth, pigs convert plant protein into animal protein. The major part of
      the ingested protein is excreted via manure, with potential nitrogen (N) losses
      to the environment. To limit N losses and increase sustainability of pork
      production, the efficiency of protein conversion should be maximized. The aim of
      this paper is to critically evaluate diet and management strategies linked with N
      efficiency. Besides nutrition, we discuss three management strategies observed in
      science and in practice to be linked with improved N efficiency: genetic
      selection, castration and slaughter weight. Because diet has a marked effect on
      eventual N losses, it must also be taken into account when evaluating management
      strategies. A reductionist approach, such as feeding the same diet across all
      management treatments, may overestimate the effect of a management strategy and
      eventually lead to incorrect conclusions. The amount of excreted N depends on the
      amount of ingested N, the amount of absorbed N, the amino acid (AA) balance in
      the diet and the animal's N and AA requirements. Daily multiphase feeding adapted
      to the individual animal's AA needs is likely to be the most N efficient. For
      animals housed in groups, phase feeding is necessary. When combined with periods
      of temporary AA restriction, N efficiency can be further improved. Specific AA
      consumption must be balanced by applying the ideal protein concept. With better
      knowledge of the requirements of individual animals and the commercial
      availability of certain AAs, the total dietary CP level can be lowered within
      limits. Further research is needed on the minimal CP level that allows maximal
      performance. For this end a useful parameter may be the ratio of standardized
      ileal digestible (SID) lysine : apparent total tract digestible CP level. By
      combining optimal nutrition and management, a whole body N efficiency approaching
      60% may be achievable in the near future.

PMID- 29065939
TI  - Relationship of runs of homozygosity with adaptive and production traits in a
      paternal broiler line.
AB  - Genomic regions under high selective pressure present specific runs of
      homozygosity (ROH), which provide valuable information on the genetic mechanisms
      underlying the adaptation to environment imposed challenges. In broiler chickens,
      the adaptation to conventional production systems in tropical environments lead
      the animals with favorable genotypes to be naturally selected, increasing the
      frequency of these alleles in the next generations. In this study, ~1400 chickens
      from a paternal broiler line were genotyped with the 600 K Affymetrix(r) Axiom(r)
      high-density (HD) genotyping array for estimation of linkage disequilibrium (LD),
      effective population size (N e ), inbreeding and ROH. The average LD between
      adjacent single nucleotide polymorphisms (SNPs) in all autosomes was 0.37, and
      the LD decay was higher in microchromosomes followed by intermediate and
      macrochromosomes. The N e of the ancestral population was high and declined over
      time maintaining a sufficient number of animals to keep the inbreeding
      coefficient of this population at low levels. The ROH analysis revealed genomic
      regions that harbor genes associated with homeostasis maintenance and immune
      system mechanisms, which may have been selected in response to heat stress. Our
      results give a comprehensive insight into the relationship between shared ROH
      regions and putative regions related to survival and production traits in a
      paternal broiler line selected for over 20 years. These findings contribute to
      the understanding of the effects of environmental and artificial selection in
      shaping the distribution of functional variants in the chicken genome.

PMID- 29065940
TI  - Consequences of dietary calcium and phosphorus depletion and repletion feeding
      sequences on growth performance and body composition of growing pigs.
AB  - The effect of a calcium (Ca) and phosphorus (P) depletion and repletion strategy
      was studied in four consecutive feeding phases of 28 days each. In all, 60
      castrated male pigs (14+/-1.6 kg initial BW) received 60% (low (L) diet;
      depletion) or 100% (control (C) diet; repletion) of their Ca and digestible P
      requirements according to six feeding sequences (CCCC, CCCL, CLCC, CCLC, LCLC and
      LLLL; subsequent letters indicate the diet received in phases 1, 2, 3 and 4,
      respectively). Pigs bone mineral content in whole-body (BMCb) and lumbar
      vertebrae L2 to L4 (BMCv) was measured in every feeding phase by dual-energy X
      ray absorptiometry. Growth performance was slightly (<10%) affected by depletion,
      however, dietary treatments did not affect overall growth. Compared with control
      pigs, depletion reduced BMCb (34%, 38%, 33% and 22%) and BMCv (46%, 54%, 38% and
      26%) in phases 1 to 4, respectively. Depletion increased however digestible P
      retention efficiency from the second to the fourth phases allowing LLLL pigs to
      present no differences in BMCb and BMCv gain compared with CCCC pigs in phase 4.
      Growth performance in repleted compared with control pigs was lower in phase 2,
      was no different in phase 3 and was lower in CLCC pigs in phase 4. Repletion
      increased body P and Ca retention efficiency when compared with control pigs
      (respectively, 8% and 10% for LC v. CC, P<0.01; 8% and 10% for CLC v. CCC,
      P<0.10; 18% and 25% for CLCC, CCLC, LCLC v. CCCC, P<0.001). Moreover, BMCv gain
      was higher in CLC pigs (P<0.001) and gains of body P, Ca, BMCb and BMCv in phase
      4 were also higher in repleted than in CCCC pigs (respectively, 14%, 20%, 20% and
      52%; P?0.02). Repletion reduced body P, Ca, BMCb and BMCv masses in phase 2 but
      no differences were found in phase 4 compared with control pigs. Lumbar vertebrae
      L2 to L4 bone mineral content was more sensitive to depletion and repletion
      sequences than BMCb especially in the first phase probably due to a higher
      proportion of metabolically active trabecular bone in vertebrae than in the whole
      skeleton. Dietary Ca was, however, oversupply in L compared with C diets (3.1 v.
      2.5 Ca:digestible P ratio, respectively) suggesting that P has probably driven
      the regulations. Phosphorus and Ca depletion and repletion increases dietary P
      utilization efficiency and can help to reduce dietary P supply, but the
      underlying mechanisms need elucidation before its practical application.

PMID- 29065941
TI  - Effects of maternal methyl donor on the pork characteristics of offspring pigs
      with prenatal exposure to bisphenol A.
AB  - To explore the effects of maternal nutrition on offspring muscle characteristics,
      a total of 56 sows were assigned to one of the four dietary groups during
      gestation: control (CON), or control diets supplemented with methyl donor (MET),
      bisphenol A (BPA), and combined BPA and MET (BPA+MET). Compared with CON
      offspring, MET offspring showed a higher meat redness value, but lower glycogen
      content in the longissimus thoracis (LT). Moreover, compared with CON offspring,
      MET offspring showed lower LT glycogen synthase (GS) mRNA levels at birth and the
      finishing stage, and increased methylation at the GS promoter. Prenatal BPA
      exposure reduced the pH and redness value of meat, but increased the lightness
      value, lactate content, glycolytic potential and lactate dehydrogenase (LDH)
      enzyme activity in the LT muscle. Prenatal BPA exposure increased LDH mRNA levels
      in the LT muscle at birth and the finishing stage, and reduced methylation at the
      LDH promoter. Thus, maternal MET affects muscle GS and LDH expression via DNA
      methylation, thereby resulting in persistent effects on pork quality.

PMID- 29065942
TI  - PERFORMANCE OF OVID MEDLINE SEARCH FILTERS TO IDENTIFY HEALTH STATE UTILITY
      STUDIES.
AB  - OBJECTIVES: This study was designed to assess the sensitivity of three Ovid
      MEDLINE search filters developed to identify studies reporting health state
      utility values (HSUVs), to improve the performance of the best performing filter,
      and to validate resulting search filters. METHODS: Three quasi-gold standard sets
      (QGS1, QGS2, QGS3) of relevant studies were harvested from reviews of studies
      reporting HSUVs. The performance of three initial filters was assessed by
      measuring their relative recall of studies in QGS1. The best performing filter
      was then developed further using QGS2. This resulted in three final search
      filters (FSF1, FSF2, and FSF3), which were validated using QGS3. RESULTS: FSF1
      (sensitivity maximizing) retrieved 132/139 records (sensitivity: 95 percent) in
      the QGS3 validation set. FSF1 had a number needed to read (NNR) of 842. FSF2
      (balancing sensitivity and precision) retrieved 128/139 records (sensitivity: 92
      percent) with a NNR of 502. FSF3 (precision maximizing) retrieved 123/139 records
      (sensitivity: 88 percent) with a NNR of 383. CONCLUSIONS: We have developed and
      validated a search filter (FSF1) to identify studies reporting HSUVs with high
      sensitivity (95 percent) and two other search filters (FSF2 and FSF3) with
      reasonably high sensitivity (92 percent and 88 percent) but greater precision,
      resulting in a lower NNR. These seem to be the first validated filters available
      for HSUVs. The availability of filters with a range of sensitivity and precision
      options enables researchers to choose the filter which is most appropriate to the
      resources available for their specific research.

PMID- 29065943
TI  - Invited review: The evolution of cattle bioacoustics and application for advanced
      dairy systems.
AB  - Vocalisations are commonly expressed by gregarious animals, including cattle, as
      a form of short- and long-distance communication. They can provide conspecifics
      with meaningful information about the physiology, affective state and physical
      attributes of the caller. In cattle, calls are individually distinct meaning they
      assist animals to identify specific individuals in the herd. Consequently, there
      is potential for these vocalisations to be acoustically analysed to make
      inferences about how individual animals or herds are coping with their external
      surroundings, and then act on these signals to improve feed conversion
      efficiency, reproductive efficiency and welfare. In the case of dairy farming,
      where herd sizes are expanding and farmers are becoming more reliant on
      technologies to assist in the monitoring of cattle, the study of vocal behaviour
      could provide an objective, cost effective and non-invasive alternative to
      traditional measures of welfare. The vocalisations of cattle in response to calf
      separation, social isolation and painful husbandry procedures, alongside changes
      to feeding and oestrous activity are here reviewed. For future application of
      sound technology, research is first necessary to analyse the acoustic structure
      of cattle vocalisations and determine the specific information they encode. This
      review draws together the latest research in field of cattle bioacoustics
      highlighting how the source-filter theory and affective state dimensional
      approach can be adopted to decode this information and improve on-farm
      management.

PMID- 29065944
TI  - Pulse therapy combined with oral corticosteroids in the management of severe
      rheumatic carditis and rebound.
AB  - OBJECTIVE: The aim of the present study was to describe the clinical course,
      laboratory tests, and the cardiac involvement in rheumatic carditis patients in
      functional class III and IV, submitted to pulse therapy combined with oral
      prednisone. METHODS: A total of 120 patients with severe carditis due to acute
      rheumatic fever were treatment with three cycles of pulse therapy combined with
      oral corticosteroids. The patients were followed up from the hospital admission
      until the end of the treatment and returned after 30, 60, and 90 days to control.
      The patients were evaluated by clinical, laboratory, and transthoracic
      echocardiogram. RESULTS: In total, 23 (19.2%) patients at first attack of
      rheumatic fever and 97 (80.8%) with recurrent carditis were evaluated. Cardiac
      surgery was performed in 8 (6.6%) patients. The patients showed improved
      laboratory and radiological parameters (p<0.001) and were discharged, 74 (61.7%)
      in functional class I and 46 (38.3%) in functional class II. Hospitalisation time
      ranged from 21 to 176 days, with a mean of 69.1 days. Reduction of left atrium
      and ventricle diameters was observed, measured by means of transthoracic
      echocardiography, at hospital admission and discharge (p<0.001). None of the
      patients experienced rebound. CONCLUSIONS: The pulse therapy was effective in
      controlling severe rheumatic carditis and the oral corticosteroid prevented
      rebound episodes. Prolonged hospital stay was required for the clinical
      stabilisation of patients and to avoid the interruption of medication.

PMID- 29065946
TI  - Genetic selection on abdominal fat content alters the reproductive performance of
      broilers.
AB  - The effects of obesity on reproduction have been widely reported in humans and
      mice. The present study was designed to compare the reproductive performance of
      lean and fat chicken lines, divergently selected for abdominal fat content. The
      following parameters were determined and analyzed in the two lines: (1)
      reproductive traits, including age at first egg and total egg numbers from
      generations 14 to 18, absolute and relative testicular weights at 7, 14, 25, 30,
      45 and 56 weeks of age, semen quality at 30, 45 and 56 weeks of age in generation
      18, and fertility and hatchability from generations 14 to 18; (2) reproductive
      hormones at 7, 14, 25, 30, 45 and 56 weeks of age in generation 18; (3) and the
      relative mRNA abundance of genes involved in reproduction at 7, 14, 25, 30, 45
      and 56 weeks of age in generation 18. In females, birds in the lean line laid
      more eggs from the first egg to 40 weeks of age than the birds in the fat line.
      In male broilers, the birds in the lean line had higher absolute and relative
      testicular weights at 7, 14 and 25 weeks of age, but lower absolute and relative
      testicular weights at 56 weeks of age than the birds in the fat line. Male birds
      in the lean line had greater sperm concentrations and larger numbers of motile
      and morphologically normal sperms at 30, 45 and 56 weeks of age than the birds in
      the fat line. Fertility and hatchability were also higher in the lean line than
      in the fat line. Significant differences in the plasma levels of reproductive
      hormones and the expression of reproduction-associated genes were also found at
      different ages in the lean and fat birds, in both males and females. These
      results suggest that reproductive performance is better in lean birds than in fat
      birds. In view of the unique divergent lines used in this study, these results
      imply that selecting for abdominal fat deposition negatively affects the
      reproductive performance of birds.

PMID- 29065945
TI  - EXAMINING EVIDENCE IN U.S. PAYER COVERAGE POLICIES FOR MULTI-GENE PANELS AND
      SEQUENCING TESTS.
AB  - OBJECTIVES: The aim of this study was to examine the evidence payers cited in
      their coverage policies for multi-gene panels and sequencing tests (panels), and
      to compare these findings with the evidence payers cited in their coverage
      policies for other types of medical interventions. METHODS: We used the
      University of California at San Francisco TRANSPERS Payer Coverage Registry to
      identify coverage policies for panels issued by five of the largest US private
      payers. We reviewed each policy and categorized the evidence cited within as:
      clinical studies, systematic reviews, technology assessments, cost-effectiveness
      analyses (CEAs), budget impact studies, and clinical guidelines. We compared the
      evidence cited in these coverage policies for panels with the evidence cited in
      policies for other intervention types (pharmaceuticals, medical devices,
      diagnostic tests and imaging, and surgical interventions) as reported in a
      previous study. RESULTS: Fifty-five coverage policies for panels were included.
      On average, payers cited clinical guidelines in 84 percent of their coverage
      policies (range, 73-100 percent), clinical studies in 69 percent (50-87 percent),
      technology assessments 47 percent (33-86 percent), systematic reviews or meta
      analyses 31 percent (7-71 percent), and CEAs 5 percent (0-7 percent). No payers
      cited budget impact studies in their policies. Payers less often cited clinical
      studies, systematic reviews, technology assessments, and CEAs in their coverage
      policies for panels than in their policies for other intervention types. Payers
      cited clinical guidelines in a comparable proportion of policies for panels and
      other technology types. CONCLUSIONS: Payers in our sample less often cited
      clinical studies and other evidence types in their coverage policies for panels
      than they did in their coverage policies for other types of medical
      interventions.

PMID- 29065947
TI  - TAKING PATIENT HETEROGENEITY AND PREFERENCES INTO ACCOUNT IN HEALTH TECHNOLOGY
      ASSESSMENTS.
AB  - OBJECTIVES: The INTEGRATE-HTA project provided methodology to evaluate complex
      technologies. This study provides guidance on how to retrieve and critically
      appraise available evidence on moderators and predictors of treatment effects and
      on patient preferences for treatment outcomes as a source of complexity. METHODS:
      Search filters for PubMed were developed by hand-searching a large volume of
      articles reporting on relevant aspects. Search terms were retrieved from selected
      papers and algorithmically combined to find the optimal combination of search
      terms. For the development of the appraisal checklists literature was searched in
      PubMed and Google Scholar together with citation chasing. For the CHecklist for
      the Appraisal of Moderators and Predictors (CHAMP) a Delphi procedure was used to
      value a set of eligible appraisal criteria retrieved from the literature.
      RESULTS: Search filters were developed optimized for different accuracy measures.
      The final version of CHAMP consists of a seventeen questions covering the design,
      analysis, results and transferability of results of moderator and predictor
      analysis. The final checklist for appraisal of literature on patient preferences
      for treatment outcomes consist of six questions meant to help the user to
      identify relevant quality issues together with a guidance toward existing tools
      concerning the appraisal of specific preference elicitation methods. CONCLUSIONS:
      Incorporating knowledge on subgroups for whom a specific treatment will produce
      more benefit holds the promise of better targeting and, ultimately, enhancing
      overall effectiveness and efficiency of healthcare technology. Finally,
      incorporating information on preferences for treatment outcomes will foster
      health technology assessment that addresses outcomes that are important to
      patients.

PMID- 29065948
TI  - Circadian rhythms, nutrition and implications for longevity in urban
      environments.
AB  - Presently, about 12% of the population is 65 years or older and by the year 2030
      that figure is expected to reach 21%. In order to promote the well-being of the
      elderly and to reduce the costs associated with health care demands, increased
      longevity should be accompanied by ageing attenuation. Energy restriction, which
      limits the amount of energy consumed to 60-70% of the daily intake, and
      intermittent fasting, which allows the food to be available ad libitum every
      other day, extend the life span of mammals and prevent or delay the onset of
      major age-related diseases, such as cancer, diabetes and cataracts. Recently, we
      have shown that well-being can be achieved by resetting of the circadian clock
      and induction of robust catabolic circadian rhythms via timed feeding. In
      addition, the clock mechanism regulates metabolism and major metabolic proteins
      are key factors in the core clock mechanism. Therefore, it is necessary to
      increase our understanding of circadian regulation over metabolism and longevity
      and to design new therapies based on this regulation. This review will explore
      the present data in the field of circadian rhythms, ageing and metabolism.

PMID- 29065949
TI  - Effects of spermine on the antioxidant status and gene expression of antioxidant
      related signaling molecules in the liver and longissimus dorsi of piglets.
AB  - Previous studies showed that spermine could protect the organism from oxidative
      damage in vivo. However, in vivo information on the antioxidant-related
      underlying molecular mechanism of spermine is limited. In this experiment, we
      further evaluated the effects of spermine supplementation and extended spermine
      administration on the antioxidant status and antioxidant-related signaling
      molecules gene expression in the liver and longissimus dorsi of piglets. A total
      of 80 piglets were randomly distributed to two groups, that is, those with
      adequate nutrient intake administrated with spermine (0.4 mmol/kg BW) or those
      with restricted nutrient intake supplemented by saline. The piglets were fed in
      pairs for 7 h or 3, 6, or 9 days. The results are as follows: (1) spermine can
      promote the antioxidant capacity by increasing enzymatic antioxidant capacity,
      glutathione content and clearance of oxygen radicals; (2) spermine significantly
      increased the mRNA levels of enzymatic antioxidant substances, NF-E2-related
      nuclear factor 2, Kelch-like ECH-associated protein 1, and the mammalian target
      of rapamycin but decreased the mRNA levels of ribosomal p70 S6 kinase in the
      liver and longissimus dorsi of the piglets.

PMID- 29065950
TI  - Indices of heart rate variability as potential early markers of metabolic stress
      and compromised regulatory capacity in dried-off high-yielding dairy cows.
AB  - High performing dairy cows experience distinct metabolic stress during periods of
      negative energy balance. Subclinical disorders of the cow's energy metabolism
      facilitate failure of adaptational responses resulting in health problems and
      reduced performance. The autonomic nervous system (ANS) with its sympathetic and
      parasympathetic branches plays a predominant role in adaption to inadequate
      energy and/or fuel availability and mediation of the stress response. Therefore,
      we hypothesize that indices of heart rate variability (HRV) that reflect ANS
      activity and sympatho-vagal balance could be early markers of metabolic stress,
      and possibly useful to predict cows with compromised regulatory capacity. In this
      study we analysed the autonomic regulation and stress level of 10 pregnant dried
      off German Holstein cows before, during and after a 10-h fasting period by using
      a wide range of HRV parameters. In addition heat production (HP), energy balance,
      feed intake, rumen fermentative activity, physical activity, non-esterified fatty
      acids, beta-hydroxybutyric acid, cortisol and total ghrelin plasma
      concentrations, and body temperature (BT) were measured. In all cows fasting
      induced immediate regulatory adjustments including increased lipolysis (84%) and
      total ghrelin levels (179%), reduction of HP (-16%), standing time (-38%) and
      heart rate (-15%). However, by analysing frequency domain parameters of HRV (high
      frequency (HF) and low-frequency (LF) components, ratio LF/HF) cows could be
      retrospectively assigned to groups reacting to food removal with increased or
      decreased activity of the parasympathetic branch of the ANS. Regression analysis
      reveals that under control conditions (feeding ad libitum) group differences were
      best predicted by the nonlinear domain HRV component Maxline (L MAX, R 2=0.76,
      threshold; TS=258). Compared with cows having L MAX values above TS (>L MAX:
      348+/-17), those with L MAX values below TS (<L MAX: 109+/-26) had higher basal
      blood cortisol levels, lower concentrations of insulin, and respond to fasting
      with a shift of their sympatho-vagal balance towards a much stronger dominance of
      the sympathetic branch of the ANS and development of stress-induced hyperthermia.
      The data indicate a higher stress level, reduced well-being and restricted
      regulatory capacity in <L MAX cows. This assumption is in accord with the lower
      dry matter intake and energy corrected milk yield (16.0+/-0.7 and 42+/-2 kg/day)
      in lactating <L MAX compared with >L MAX cows (18.5+/-0.4 and 47.3 kg/day). From
      the present study, it seems conceivable that L MAX can be used as a predictive
      marker to discover alterations in central autonomic regulation that might precede
      metabolic disturbances.

PMID- 29065951
TI  - Determination of Total Steroid Saponins in Different Species of Paris Using FTIR
      Combined with Chemometrics.
AB  - The saponins of Paris spp. have antimicrobial, immune-stimulating, and antitumor
      biological properties. In this investigation, FTIR and ultra-HPLC (UHPLC) were
      used for the determination of total steroid saponins in different species of
      Paris from Yunnan Province, China. A 52-sample calibration set and a 26-sample
      validation set for partial least-squares regression (PLSR) and support vector
      machine regression (SVMR) combined with FTIR and UHPLC were investigated. The
      optimal parameters C and gamma were screened by a grid search with a sevenfold
      cross-validation. The results indicate that pretreatment with the combination of
      standard normal variate, second derivative, and orthogonal signal correction had
      the best performance. When comparing the SVMR and PLSR models, linear PLSR had
      better performance than nonlinear SVMR for the determination of total steroid
      saponins in different species of Paris. The highest total saponin content was
      found in P. axialis from Baoshan City (40.92 +/- 9.06 mg/g). These results
      demonstrate that this approach would provide a fast and robust strategy for the
      QC of Paris in further analyses.

PMID- 29065952
TI  - Barriers to CPAP Use in India: An Exploratory Study.
AB  - STUDY OBJECTIVES: To investigate adherence to continuous positive airway pressure
      (CPAP) therapy and identify barriers to CPAP use among patients with obstructive
      sleep apnea (OSA) in India. METHODS: A self-devised semistructured questionnaire
      (which collected patients' demographic information, socioeconomic position, and
      information about disease status, symptoms, and complications) was administered
      to consecutive patients with moderate to severe OSA from June 2015 to August
      2016. Patients were grouped according to CPAP device buying behavior (buyers
      versus nonbuyers) and CPAP compliance behavior (compliant versus noncompliant).
      RESULTS: Out of 187 patients with moderate-severe OSA, 79 patients were enrolled
      for this study. The overall adherence rate (usage > 4 hours per night on > 70%
      nights) was 30.3%. Among the patients in the buyer group, adherence was 82.7%.
      Fifty patients did not buy a CPAP device; 30 of these 50 patients (60%) said
      financial constraints were the most important reason for not buying a CPAP
      device. Patients without financial constraints had higher chances-odds ratio (95%
      confidence interval) = 4.85 (1.6-16.1)-of buying a CPAP device than patients with
      financial constraints. Patients with more severe disease (ie, lower nadir oxygen
      saturation during sleep, higher apnea-hypopnea index, or presence of obesity
      hypoventilation syndrome) were more likely to buy and use a CPAP device.
      CONCLUSIONS: The main cause of nonuse of CPAP in India is the inability to buy a
      CPAP device. In patients who are able to buy a CPAP device, adherence was
      significantly higher (82.7%) compared to adherence in the study's overall
      population (30.3%). Furthermore, patients with more severe OSA were more likely
      to buy a device and adhere to CPAP. Patients' behaviors and attitudes are also
      important barriers in using CPAP. There needs to be increased awareness of the
      benefits of CPAP therapy among patients.

PMID- 29065954
TI  - The Relationship Between Obstructive Sleep Apnea and Ruptured Intracranial
      Aneurysms.
AB  - STUDY OBJECTIVES: The role of obstructive sleep apnea (OSA) in the overall
      outcome of ruptured intracranial aneurysms (RIAs) is unknown. We have
      investigated the role of OSA in overall outcome of RIAs. METHODS: Data from 159
      consecutive patients were retrospectively reviewed. A chi-square test and
      regression analysis were performed to determine the significant difference. A
      value of P< .05 was considered significant. RESULTS: The prevalence of OSA in
      RIAs was fivefold higher in the nonaneurysm patient group, P = .002. The number
      of patients with hypertension (P< .0001), body mass index >= 30 (P< .0001),
      hyperlipidemia (P = .018), chronic heart disease (P = .002) or prior ischemic
      stroke (P = .001) was significantly higher in the OSA group. Similarly, the
      number of wide-neck aneurysms (P< .0001) and aneurysm > 7 mm (P = .004), poor
      Hunt and Hess grade IV-V (P = .005), vasospasms, (P = .03), and patients with
      poor Modified Rankin Scale scores (3-6) was significantly higher in the OSA group
      (P< .0001). Interestingly, for the first time in univariate (P = .01) and
      multivariate (P = .003) regression analysis, OSA was identified as an individual
      predictor of unfavorable outcome of RIAs. In addition, hypertension (P = .04),
      smoking (P = .049), chronic heart disease (P = .01), and Hunt and Hess grade IV-V
      (P = .04) were revealed as predictors of poor outcome of RIAs. CONCLUSIONS: This
      is a novel study to determine the association between OSA and ruptured cerebral
      aneurysm in terms of comorbidities, size of aneurysm, severity of symptoms, and
      outcomes after treatment. In addition, for the first time, OSA is identified as a
      positive predictor of unfavorable outcome of RIAs.

PMID- 29065953
TI  - Lemborexant, A Dual Orexin Receptor Antagonist (DORA) for the Treatment of
      Insomnia Disorder: Results From a Bayesian, Adaptive, Randomized, Double-Blind,
      Placebo-Controlled Study.
AB  - STUDY OBJECTIVES: To identify dose(s) of lemborexant that maximize insomnia
      treatment efficacy while minimizing next-morning residual sleepiness and evaluate
      lemborexant effects on polysomnography (PSG) measures (sleep efficiency [SE],
      latency to persistent sleep [LPS], and wake after sleep onset [WASO]) at the
      beginning and end of treatment. METHODS: Adults and elderly subjects with
      insomnia disorder per the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition were enrolled in a multicenter, randomized, double-blind, placebo
      controlled, Bayesian, adaptive, parallel-group study, receiving lemborexant (1,
      2.5, 5, 10, 15, 25 mg) or placebo for 15 nights. Efficacy assessments included a
      utility function that combined efficacy (SE) and safety (residual morning
      sleepiness as measured by Karolinska Sleepiness Scale [KSS]), PSG measures, and
      sleep diary. Safety assessments included KSS, Digit Symbol Substitution Test,
      computerized reaction time tests, and adverse events (AEs). RESULTS: A total of
      616 subjects were screened; 291 were randomized. Baseline characteristics were
      similar between lemborexant groups and placebo (~63% female, median age: 49.0
      years). The study was stopped for early success after the fifth interim analysis
      when the 15-mg dose met utility index/KSS criteria for success; 3 other doses
      also met the criteria. Compared with placebo, subjects showed significant
      improvements in SE, subjective SE, LPS, and subjective sleep onset latency at the
      beginning and end of treatment for lemborexant doses >= 5 mg (P < .05). WASO and
      subjective WASO showed numerically greater improvements for doses > 1 mg. AEs,
      mostly mild to moderate, included dose-related somnolence. CONCLUSIONS:
      Lemborexant doses ranging from 2.5-10 mg provided efficacy for the treatment of
      insomnia while minimizing next-morning residual sleepiness. CLINICAL TRIAL
      REGISTRATION: Title: A Multicenter, Randomized, Double-blind, Placebo-controlled,
      Parallel-group, Bayesian Adaptive Randomization Design, Dose Response Study of
      the Efficacy of E2006 in Adults and Elderly Subjects With Chronic Insomnia; URL:
      https://clinicaltrials.gov/ct2/show/NCT01995838; Identifier: NCT01995838.

PMID- 29065955
TI  - CPAP Adherence is Associated With Attentional Improvements in a Group of
      Primarily Male Patients With Moderate to Severe OSA.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a widespread condition that
      adversely affects physical health and cognitive functioning. The prevailing
      treatment for OSA is continuous positive airway pressure (CPAP), but therapeutic
      benefits are dependent on consistent use. Our goal was to investigate the
      relationship between CPAP adherence and measures of sustained attention in
      patients with OSA. Our hypothesis was that the Psychomotor Vigilance Task (PVT)
      would be sensitive to attention-related improvements resulting from CPAP use.
      METHODS: This study was a secondary analysis of a larger clinical trial.
      Treatment adherence was determined from CPAP use data. Validated sleep-related
      questionnaires and a sustained-attention and alertness test (PVT) were
      administered to participants at baseline and at the 6-month time point. RESULTS:
      Over a 6-month time period, the average CPAP adherence was 3.32 h/night (standard
      deviation [SD] = 2.53), average improvement in PVT minor lapses was -4.77 (SD =
      13.2), and average improvement in PVT reaction time was -73.1 milliseconds
      (standard deviation = 211). Multiple linear regression analysis showed that
      higher CPAP adherence was significantly associated with a greater reduction in
      minor lapses in attention after 6 months of continuous treatment with CPAP
      therapy (beta = -0.72, standard error = 0.34, P = .037). CONCLUSIONS: The results
      of this study showed that higher levels of CPAP adherence were associated with
      significant improvements in vigilance. Because the PVT is a performance-based
      measure that is not influenced by prior learning and is not subjective, it may be
      an important supplement to patient self-reported assessments. CLINICAL TRIAL
      REGISTRATION: Name: Effect of Self-Management on Improving Sleep Apnea Outcomes,
      URL: https://clinicaltrials.gov/ct2/show/NCT00310310, Identifier: NCT00310310.

PMID- 29065956
TI  - Distinct Patterns of Hyperpnea During Cheyne-Stokes Respiration: Implication for
      Cardiac Function in Patients With Heart Failure.
AB  - STUDY OBJECTIVES: In heart failure (HF), we observed two patterns of hyperpnea
      during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA): a positive
      pattern where end-expiratory lung volume remains at or above functional residual
      capacity, and a negative pattern where it falls below functional residual
      capacity. We hypothesized the negative pattern is associated with worse HF.
      METHODS: Patients with HF underwent polysomnography. During CSR-CSA, hyperpnea,
      apnea-hyperpnea cycle, and lung to finger circulation times (LFCT) were measured.
      Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP)
      concentration and left ventricular ejection fraction (LVEF) were assessed.
      RESULTS: Of 33 patients with CSR-CSA (31 men, mean age 68 years), 9 had a
      negative hyperpnea pattern. There was no difference in age, body mass index, and
      apnea-hypopnea index between groups. Patients with a negative pattern had longer
      hyperpnea time (39.5 +/- 6.4 versus 25.8 +/- 5.9 seconds, P < .01), longer cycle
      time (67.8 +/- 15.9 versus 51.7 +/- 9.9 seconds, P < .01), higher NT-proBNP
      concentrations (2740 [6769] versus 570 [864] pg/ml, P = .01), and worse New York
      Heart Association class (P = .02) than those with a positive pattern. LFCT and
      LVEF did not differ between groups. CONCLUSIONS: Patients with HF and a negative
      CSR-CSA pattern have evidence of worse cardiac function than those with a
      positive pattern. Greater positive expiratory pressure during hyperpnea is likely
      generated during the negative pattern and might support stroke volume in patients
      with worse cardiac function. COMMENTARY: A commentary on this article appears in
      this issue on page 1227. CLINICAL TRIAL REGISTRATION: The trial is registered
      with Current Controlled Trials (www.controlled-trials.com; ISRCTN67500535) and
      Clinical Trials (www.clinicaltrials.gov; NCT01128816).

PMID- 29065958
TI  - Dissociation of Objective and Subjective Daytime Sleepiness and Biomarkers of
      Systemic Inflammation in Sleep-Disordered Breathing and Systolic Heart Failure.
AB  - STUDY OBJECTIVES: Subjective versus objective sleepiness in heart failure (HF)
      remains understudied; therefore, we sought to examine the association of these
      measures and interrelationships with biochemical markers. METHODS: Participants
      with stable systolic HF recruited from a clinic-based program underwent attended
      polysomnography, Multiple Sleep Latency Testing, questionnaire data collection
      including Epworth Sleepiness Scale (ESS), and morning phlebotomy for biochemical
      markers. Linear regression was used to assess the association of mean sleep
      latency (MSL) and ESS (and other reported outcomes) with adjustment of age or
      body mass index or left ventricular ejection fraction (LVEF) (beta coefficients,
      95% confidence interval) and also with biochemical markers (beta coefficients,
      95% confidence interval). RESULTS: The final analytic sample comprised 26
      participants: 52 +/- 14 years with apnea-hypopnea index (AHI): 34 +/- 27, LVEF:
      34 +/- 12%, MSL: 7 +/- 5 minutes and ESS: 7 (5, 10). There was no significant
      association of MSL and ESS (-0.36, -0.81 to 0.09, P = .11), AHI, or other
      questionnaire-based outcomes in adjusted analyses. Although statistically
      significant associations of ESS and biomarkers were not observed, there were
      associations of MSL and cortisol (MUg/dL) [-0.05: -0.08, -0.01, P = .012] and
      interleukin-6 (pg/mL) [-0.11: -0.18, -0.04, P = .006], which persisted in
      adjusted models. CONCLUSIONS: In systolic HF, although overall objective
      sleepiness was observed, this was not associated with subjective sleepiness (ie,
      a discordance was identified). Differential upregulation of systemic inflammation
      in objective sleepiness was observed, findings not observed with subjective
      sleepiness. These findings suggest that underlying mechanistic pathways of
      inflammation may provide the explanation for dissonance of objective and
      subjective sleepiness symptoms in HF, thus potentially informing targeted
      diagnostic and therapeutic approaches. COMMENTARY: A commentary on this article
      appears in this issue on page 1369.

PMID- 29065957
TI  - Changes in Caregiving Status and Intensity and Sleep Characteristics Among High
      and Low Stressed Older Women.
AB  - STUDY OBJECTIVES: To examine whether change in caregiving status and intensity
      among community-dwelling older women was associated with sleep characteristics at
      follow-up, and whether perceived stress modified these associations. METHODS: The
      sample included 800 women aged 65 years or older who completed baseline and
      second follow-up interviews in the Caregiver-Study of Osteoporotic Fractures
      (Caregiver-SOF). Respondents were categorized into four groups based on change in
      caregiving status and intensity between the two time points: continuous
      noncaregivers, ceased caregivers, low-intensity caregivers (continuous caregivers
      with low/decreased intensity), and high-intensity caregivers (continuous
      caregivers with high/increased intensity or new caregivers). Perceived Stress
      Scale scores at the second follow-up were dichotomized into high versus low
      stress. Sleep outcomes at SOF Visit 8 (which overlapped with Caregiver-SOF second
      follow-up) included the Pittsburgh Sleep Quality Index total score; and
      actigraphy-measured total sleep time, sleep efficiency, wake after sleep onset,
      and sleep latency. RESULTS: Multivariate-adjusted sleep characteristics did not
      differ significantly across caregiving groups. Among high-intensity caregivers,
      however, those with high stress levels had significantly longer wake after sleep
      onset (mean 82.3 minutes, 95% confidence interval = 70.9-93.7) than those with
      low stress levels (mean 65.4 minutes, 95% confidence interval = 55.2-75.7). No
      other sleep outcomes were modified by stress levels. Further, higher stress was
      significantly associated with worse Pittsburgh Sleep Quality Index scores,
      regardless of the caregiving group. CONCLUSIONS: Overall, sleep characteristics
      did not differ among noncaregivers, ceased caregivers, or those with high-/low
      intensity caregiving among older women. However, subgroups of caregivers may be
      vulnerable to developing sleep problems, particularly those with high stress
      levels.

PMID- 29065959
TI  - Nocturnal Hypoxemia is Associated With Low Testosterone Levels in Overweight
      Males and Older Men With Normal Weight.
AB  - STUDY OBJECTIVES: The relationship among obstructive sleep apnea (OSA), body mass
      index (BMI), and testosterone levels has long been suggested. Obese men have
      shown a negative correlation between testosterone level and sleep apnea severity.
      Yet, little is known about the association between testosterone levels and sleep
      apnea in men who are not obese. This study evaluated the association between the
      total testosterone (TT) level and OSA in patients who are not obese. METHODS: A
      retrospective review of 523 records of patients in whom OSA was diagnosed from
      2013-2016 was performed. The study included men with a BMI < 30 kg/m2 and with TT
      levels measured in a blood sample collected the morning after a sleep study.
      RESULTS: In all, 153 nonobese men met inclusion criteria, of whom 47 (30.7%) had
      testosterone levels below the reference values; 44 of these individuals (93.6%)
      were overweight (P = .029). Reduced testosterone levels showed significant
      correlations with the oxygen desaturation index, the lowest oxygen saturation <
      80% (O2 nadir < 80%), and rapid eye movement (REM) sleep duration, after
      adjusting for BMI. Among patients with normal weight, only 3 who had O2 nadir <
      80% and were older than 50 years presented with a reduced TT level. CONCLUSIONS:
      In a large population of nonobese men with OSA, we demonstrated that hypoxemia
      (O2 nadir < 80%) and overweight are associated with reduced testosterone levels.
      This association was only observed among normal-weight individuals older than 50
      years.

PMID- 29065960
TI  - A Randomized Crossover Trial Evaluating Continuous Positive Airway Pressure
      Versus Mandibular Advancement Device on Health Outcomes in Veterans With
      Posttraumatic Stress Disorder.
AB  - STUDY OBJECTIVES: Despite the overall improvement in posttraumatic stress
      disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP)
      therapy, adherence to CPAP is far worse in veterans with PTSD compared to the
      general population with obstructive sleep apnea (OSA). The aim of this study was
      to compare the efficacy, adherence, and preference of CPAP versus mandibular
      advancement device (MAD) and the effect of these treatments on health outcomes in
      veterans with PTSD. METHODS: Forty-two subjects with PTSD and newly diagnosed OSA
      by polysomnography were treated in a randomized, crossover trial of 12 weeks with
      CPAP alternating with MAD separated by a 2-week washout period. The primary
      outcome was the difference in titration residual apnea-hypopnea index (AHI)
      between CPAP and MAD. Secondary outcome measures included PTSD Checklist and
      health-related quality of life (Medical Outcomes Study 36-Item Short Form and
      Pittsburgh Sleep Quality Index). RESULTS: Analyses were limited to the 35
      subjects (mean age 52.7 +/- 11.6 years) who completed the trial, regardless of
      compliance with their assigned treatment. CPAP was more efficacious in reducing
      AHI and improving nocturnal oxygenation than MAD (P < .001 and P = .04,
      respectively). Both treatments reduced PTSD severity and ameliorated scores of
      the Medical Outcomes Study Short Form 36 and Pittsburgh Sleep Quality Index,
      although no differences were detected between the CPAP and MAD arms. The reported
      adherence to MAD was significantly higher than CPAP (P < .001), with 58%
      preferring MAD to CPAP. CONCLUSIONS: Although CPAP is more efficacious than MAD
      at improving sleep apnea, both treatment modalities imparted comparable benefits
      for veterans with PTSD in relation to PTSD severity and health-related quality of
      life. MAD offers a viable alternative for veterans with OSA and PTSD who are
      nonadherent to CPAP. CLINICAL TRIAL REGISTRATION: Title: A Randomized Cross Over
      Trial of Two Treatments for Sleep Apnea in Veterans With Post-Traumatic Stress
      Disorder; URL: https://www.clinicaltrials.gov/ct/show/NCT01569022; Identifier:
      NCT01569022.

PMID- 29065962
TI  - Disordered Consciousness or Disordered Wakefulness? The Importance of Prolonged
      Polysomnography for the Diagnosis, Drug Therapy, and Rehabilitation of an
      Unresponsive Patient With Brain Injury.
AB  - ABSTRACT: Disorders of consciousness may follow brain injury, due to impairments
      of wakefulness and/or awareness. Polysomnography can identify elements that may
      be ascribed to impairments of specific neuroanatomical areas. Recognizing which
      impairments affect each patient is crucial for diagnosis, prognosis, and to
      select an appropriate therapy. We present a pediatric case of insufficient
      wakefulness in a patient with severe disability following a pilocytic
      astrocytoma. Polysomnography was crucial for diagnosis, as it detected a well
      structured pattern with daytime sleep initiations in the REM sleep phase.
      Treatment with modafinil was successful, as confirmed by polysomnography, leading
      to partial recovery of the patient's consciousness and communication ability. We
      suggest that polysomnography is a useful diagnostic tool to direct the
      pharmacotherapy and rehabilitation of states of reduced consciousness.

PMID- 29065964
TI  - Sleep Apnea and Nocturnal Cardiac Arrhythmia: Understanding Differences Across
      Ethnicity.

PMID- 29065963
TI  - Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed
      With Neonatal Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: Neurocognitive deficits have been shown in school-aged children
      with sleep apnea. The effect of obstructive sleep apnea (OSA) on the
      neurodevelopmental outcome of preterm infants is unknown. METHODS: A
      retrospective chart review was performed for all preterm infants (< 37 weeks) who
      had neonatal polysomnography (PSG) and completed neurodevelopmental assessment
      with the Bayley Scales of Infant and Toddler Development, 3rd Edition, between
      2006 to 2015 at Riley Hospital. Exclusion criteria included grade IV
      intraventricular hemorrhage, tracheostomy, cyanotic heart disease, severe
      retinopathy of prematurity, craniofacial anomalies, or central and mixed apnea on
      PSG. Sleep apnea was defined as an apnea-hypopnea index (AHI) > 1 event/h.
      Regression analyses were performed to find a relationship between PSG parameters
      and cognitive, language, and motor scores. RESULTS: Fifteen patients (males: n =
      10) were eligible for the study. Median postmenstrual age at the time of the PSG
      was 41 weeks (37-46). Median AHI for the cohort was 17.4 events/h (2.2-41.3).
      Median cognitive, language, and motor scores were 90 (65-125), 89 (65-121), and
      91 (61-112), respectively. Mean end-tidal CO2 (median 47 mm Hg [25-60])
      negatively correlated with cognitive scores (P = .01) but did not significantly
      correlate with language or motor scores. AHI was not associated with cognitive,
      language, or motor scores. CONCLUSIONS: The median score for cognitive, language,
      and motor scores for preterm infants with neonatal OSA were within one standard
      deviation of the published norm. Mean end-tidal CO2, independent of AHI, may
      serve as a biomarker for predicting poor cognitive outcome in preterm infants
      with neonatal OSA. COMMENTARY: A commentary on this article appears in this issue
      on page 1233.

PMID- 29065961
TI  - Nocturnal Desaturation is Associated With Neurological Deterioration Following
      Ischemic Stroke: A Retrospective Observational Study.
AB  - STUDY OBJECTIVES: The mechanism of early neurological deterioration (END) in
      patients with stroke remains unclear. We assessed the relationship between
      nocturnal oxygen desaturation (NOD) in the stroke unit (SU) and END, especially
      occurring at nighttime, following acute stroke. METHODS: A retrospective analysis
      was performed on a total of 276 patients with ischemic stroke who were admitted
      to the SU between July 2013 and June 2015. The oxygen desaturation index was
      calculated from pulse oximetry data sampled every 1 minute during 9 hours on the
      first night (10:00 PM to 7:00 AM) after admission, and NOD was defined as oxygen
      desaturation index >= 5 events/h. END was defined as an increase of >= 2 points
      from the baseline National Institutes of Health Stroke Scale during 7 days after
      onset. We compared clinical characteristics and NOD between patients with and
      without END. RESULTS: Among the included patients (mean age 69.2; male 55.4%), 42
      patients (15.2%) experienced END. The proportion of NOD was significantly greater
      in the END group (45.2% versus 12.8%, P < .001). After adjusting for confounders,
      NOD was independently associated with END (odds ratio 7.57; 95% confidence
      interval 3.14-18.27). Among END patients, 47.6% patients (n = 20) had END during
      nighttime. Moreover, NOD was more frequent in patients with END during nighttime
      compared to those with END during daytime (73.7% versus 26.1%, P = .002).
      CONCLUSIONS: NOD in the SU was associated with END, especially during nighttime,
      after ischemic stroke. This suggests that treatment of sleep-disordered breathing
      could be a modifiable factor to possibly reduce the risk of neurological
      worsening among acute stroke patients.

PMID- 29065965
TI  - Identification of specifically activated angiogenic molecules in HMGB-1-induced
      angiogenesis.
AB  - High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its
      dysregulated expression correlates with inflammatory diseases, ischemia, and
      cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis.
      Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown.
      In this study, we performed time-dependent DNA microarray analysis of endothelial
      cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set
      upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways
      were also activated by VEGF, although the activation time and gene sets belonging
      to the pathways differed. In addition, HMGB-1 upregulated some VEGFR signaling
      related angiogenic factors including EGR1 and, importantly, novel angiogenic
      factors, such as ABL2, CEACAM1, KIT, and VIPR1, which are reported to
      independently promote angiogenesis under physiological and pathological
      conditions. Our findings suggest that HMGB-1 independently induces angiogenesis
      by activating HMGB-1-specific angiogenic factors and also functions as an
      accelerator for VEGF-mediated conventional angiogenesis. [BMB Reports 2017;
      50(11): 590-595].

PMID- 29065966
TI  - Gastrin-releasing peptide promotes the migration of vascular smooth muscle cells
      through upregulation of matrix metalloproteinase-2 and -9.
AB  - Gastrin-releasing peptide (GRP) has been reported to be implicated in the
      pathogenesis of inflammatory disorders. The migration and proliferation of
      vascular smooth muscle cells (VSMCs) are key components of vascular inflammation
      that leads to the development of atherosclerosis. The present study aimed to
      investigate the molecular effect of GRP on VSMC proliferation and migration. We
      report that GRP significantly enhanced the proliferation and migration of rat
      VSMCs. GRP increased mRNA and protein expression of matrix metalloproteinase- 2
      and -9 (MMP-2/9) in VSMCs. The induction of MMP-2/9 by GRP was regulated by the
      activation of the signal transducer and activator of transcription-3 (STAT3). In
      addition, STAT3-knockdown of VSMCs by siRNA or blockade of the GRP receptor
      inhibited GRP-induced migration of VSMCs. Taken together, our findings indicate
      that GRP promotes the migration of VSMCs through upregulation of MMP-2/9 via
      STAT3 activation. [BMB Reports 2017; 50(12): 628-633].

PMID- 29065967
TI  - PD-1 deficiency protects experimental colitis via alteration of gut microbiota.
AB  - Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal
      role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis
      of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting
      disease during experimentally induced colitis, while mice deficient for PD-1 (PD
      1-/-) did not develop colon inflammation. Interestingly, PD-1-/- mice cohoused
      with WT mice became susceptible to colitis, suggesting that resistance of PD-1-/-
      mice to colitis is dependent on their gut microbiota. 16S rRNA gene
      pyrosequencing analysis showed that PD-1-/- mice had altered composition of gut
      microbiota with significant reduction in Rikenellaceae family. These altered
      colon bacteria of PD-1-/- mice induced less amount of inflammatory mediators from
      colon epithelial cells, including interleukin (IL)-6, and inflammatory
      chemokines. Taken together, our study indicates that PD-1 expression is involved
      in the resistance to experimental colitis through altered bacterial communities
      of colon. [BMB Reports 2017; 50(11): 578-583].

PMID- 29065968
TI  - Protein tyrosine phosphatase PTPN21 acts as a negative regulator of ICAM-1 by
      dephosphorylating IKKbeta in TNF-alpha-stimulated human keratinocytes.
AB  - Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis
      factor (TNF)-alpha, contributes to the entry of immune cells into the site of
      inflammation in the skin. Here, we show that protein tyrosine phosphatase non
      receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human
      keratinocytes. PTPN21 expression was transiently induced after stimulation with
      TNF-alpha. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT
      cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to
      inhibit ICAM-1 expression. Nuclear factor-kappaB (NF-kappaB), a key transcription
      factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21
      C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of kappaB (IkappaB)
      kinase beta (IKKbeta) at Ser177/181. This dephosphorylation led to the
      stabilization of IkappaBalpha and inhibition of NF-kappaB activity. Taken
      together, our results suggest that PTPN21 could be a valuable molecular target
      for regulation of inflammation in the skin by dephosphorylating p-IKKbeta and
      inhibiting NF-kappaB signaling. [BMB Reports 2017; 50(11): 584-589].

PMID- 29065969
TI  - Antioxidant effects of selenocysteine on replicative senescence in human adipose
      derived mesenchymal stem cells.
AB  - In most clinical applications, human mesenchymal stem cells (hMSCs) are expanded
      in large scale before their administration. Prolonged culture in vitro results in
      cellular senescenceassociated phenotypes, including accumulation of reactive
      oxygen species (ROS) and decreased cell viabilities. Profiling of stem cell
      related genes during in vitro expansion revealed that numerous canonical pathways
      were significantly changed. To determine the effect of selenocysteine (Sec), a
      rare amino acid found in several antioxidant enzymes, on the replicative
      senescence in hMSCs, we treated senescent hMSCs with Sec. Supplementation of Sec
      in the culture medium in late-passage hMSCs reduced ROS levels and improved the
      survival of hMSCs. In addition, a subset of key antioxidant genes and Sec
      containing selenoproteins showed increased mRNA levels after Sec treatment.
      Furthermore, ROS metabolism and inflammation pathways were predicted to be
      downregulated. Taken together, our results suggest that Sec has antioxidant
      effects on the replicative senescence of hMSCs. [BMB Reports 2017; 50(11): 572
      577].

PMID- 29065970
TI  - Zinc finger protein 143 expression is closely related to tumor malignancy via
      regulating cell motility in breast cancer.
AB  - We previously reported the involvement of zinc-finger protein 143 (ZNF143) on
      cancer cell motility in colon cancer cells. Here, ZNF143 was further
      characterized in breast cancer. Immunohistochemistry was used to determine the
      expression of ZNF143 in normal tissues and in tissues from metastatic breast
      cancer at various stages. Notably, ZNF143 was selectively expressed in duct and
      gland epithelium of normal breast tissues, which decreased when the tissue became
      malignant. To determine the molecular mechanism how ZNF143 affects breast cancer
      progression, it was knocked down by infecting benign breast cancer cells with
      shorthairpin (sh) RNA-lentiviral particles against ZNF143 (MCF7 sh-ZNF143). MCF7
      sh-ZNF143 cells showed different cell-cell contacts and actin filament (F-actin)
      structures when compared with MCF7 sh-Control cells. In migration and invasion
      assays, ZNF143 knockdown induced increased cellular motility in breast carcinoma
      cells. This was reduced by the recovery of ZNF143 expression. Taken together,
      these results suggest that ZNF143 expression contributes to breast cancer
      progression. [BMB Reports 2017; 50(12): 621-627].

PMID- 29065972
TI  - Hypoxia suffocates histone demethylases to change gene expression: a metabolic
      control of histone methylation.
AB  - Hypoxia affects various physiological and pathophyological processes. Hypoxia
      changes the expression of hypoxiaresponsive genes through two main pathways.
      First, hypoxia activates transcription factors (TF) such as Hypoxia-inducible
      Factor (HIF). Second, hypoxia decreases the activity of Jumonji C domain
      containing histone demethylases (JMJDs) that require O2 and alpha-Ketoglutarate
      (alpha-KG) as substrates. The JMJDs affect gene expression through their
      regulation of active or repressive histone methylations. Profiling of H3K4me3,
      H3K9me3, and H3K27me3 under both normoxia and hypoxia identified 75 TFs whose
      binding motifs were significantly enriched in the methylated regions of the
      genes. TFs showing similar binding strengths to their target genes might be under
      the 'metabolic control' which changes histone methylation and gene expression by
      instant changing catalytic activities of resident histone demethylases. [BMB
      Reports 2017; 50(11): 537-538].

PMID- 29065971
TI  - Anti-inflammatory and anti-oxidative effects of 3-(naphthalen-2
      yl(propoxy)methyl)azetidine hydrochloride on beta-amyloid-induced microglial
      activation.
AB  - We aimed to assess the anti-inflammatory and antioxidative properties of
      KHG26792, a novel azetidine derivative, in amyloid beta (Abeta)-treated primary
      microglial cells. KHG26792 attenuated the Abeta-induced production of
      inflammatory mediators such as IL-6, IL-1beta, TNF-alpha, and nitric oxide. The
      levels of protein oxidation, lipid peroxidation, ROS, and NADHP oxidase enhanced
      by Abeta were also downregulated by KHG26792 treatment. The effects of KHG26792
      against the Abeta-induced increases in inflammatory cytokine levels and oxidative
      stress were achieved by increasing the phosphorylation of Akt/ GSK-3beta
      signaling and by decreasing the Abeta-induced translocation of NF-kappaB. Our
      results provide novel insights into the use of KHG26792 as a potential agent
      against Abeta toxicity, including its role in the reduction of inflammation and
      oxidative stress. Nevertheless, further investigations of cellular signaling are
      required to clarify the in vivo effects of KHG26792 against Abeta-induced
      toxicity. [BMB Reports 2017; 50(12): 634-639].

PMID- 29065973
TI  - Pro-tumorigenic roles of TGF-beta signaling during the early stages of liver
      tumorigenesis through upregulation of Snail.
AB  - Many studies have focused on the tumor suppressive role of TGF-beta signaling
      during the early stages of tumorigenesis by activating the target genes involved
      in cytostasis and apoptosis. We investigated the effects of TGF-beta inhibition
      on early tumorigenesis in the liver, by employing diverse inhibitory methods.
      Strikingly, TGF-beta inhibition consistently suppressed hepatic tumorigenesis
      that was induced either by activated RAS plus p53 downregulation or by the co
      activation of RAS and TAZ signaling; this demonstrates the requirements for
      canonical TGF-beta signaling in tumorigenesis. Moreover, we found that Snail is
      the target gene of the TGF-beta signaling pathway that promotes hepatic
      carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the
      liver, as did the TGF-beta inhibition, while the ectopic expression of Snail
      restored tumorigenesis that was suppressed by the TGF-beta inhibition. Our
      findings establish the oncogenic TGF-beta-Smad- Snail signaling axis during the
      early tumorigenesis in the liver. [BMB Reports 2017; 50(12): 599-600].

PMID- 29065974
TI  - Seminal plasma and cryopreservation alter ram sperm surface carbohydrates and
      interactions with neutrophils.
AB  - Spermatozoa deposited vaginally must navigate the physical, chemical and immune
      barriers of the cervix to reach the site of fertilisation. Characteristics that
      favour successful cervical transit remain largely unknown beyond the obvious
      factors of motility and viability. Epididymal and cryopreserved ram spermatozoa
      demonstrate poor cervical transit, for unknown reasons. We hypothesised that
      seminal plasma exposure and cryopreservation alter the surface sugars of these
      sperm populations and, consequently, their interaction with immune cells, both
      potential factors for successful cervical transit. The carbohydrate profiles of
      epididymal, ejaculated and frozen-thawed ram spermatozoa were assessed by flow
      cytometry and western blotting using lectins for galactose, sialic acid, N
      acetylglucosamine and mannose. Seminal plasma exposure and cryopreservation
      caused significant changes to the relative amounts of surface sugars detected by
      flow cytometry and lectin blotting. Immune cell interaction was characterised
      using a neutrophil-binding assay. Seminal plasma acted as a robust protective
      mechanism, limiting binding of spermatozoa, whereas the media used for
      cryopreservation caused a significant disruption to opsonin-mediated binding. We
      were unable to demonstrate a link between changes to surface sugars and
      neutrophil susceptibility. Seminal plasma and cryopreservation clearly alter the
      sperm glycocalyx, as well as the interaction of spermatozoa with immune cells.

PMID- 29065975
TI  - Clinical Neuropathology 6-2017.

PMID- 29065976
TI  - Contrast-induced acute kidney injury - Radiology perspective.

PMID- 29065978
TI  - Contrast-induced acute kidney injury - Transforming nihilism into effective
      policy in contrast-induced acute kidney injury.

PMID- 29065977
TI  - Contrast-induced acute kidney injury - Nephrology perspective.

PMID- 29065979
TI  - Not all immune-checkpoint inhibitors are created equal: Meta-analysis and
      systematic review of immune-related adverse events in cancer trials.
AB  - BACKGROUND: Targeting immune checkpoints is a novel approach in cancer therapy.
      This strategy may trigger immune related adverse events (irAE). We hypothesize
      that the incidence of irAE will be greater in patients receiving immune
      checkpoint inhibitors (ICI) targeting only immune cells compared to those that
      also target tumor cells (PD-L1). In addition, we compared the specific irAE
      profile and overall response rate (ORR) for each ICI by target(s). MATERIALS AND
      METHODS: We reviewed all ICI cancer clinical trials (90; 174 arms) that reported
      irAE and were published through MEDLINE. 114 arms from 73 trials were eligible
      for this meta-analysis (including 11,328 patients). We collected and compared arm
      specific data including ICI target, number of patients with irAE of any grade,
      grade 3+ and grade 5, specific irAE, and ORR. The R package "meta" was used to
      conduct a meta-analysis to calculate and compare the percentage of patients with
      irAE and ORR. RESULTS: The incidence (% of patients) of any grade irAE per ICI
      target was reported for 40 arms (3418 patients) treated with ICI. Most arms (80%)
      and patients (53%) studied were on phase 1/2 clinical trials. Patients were
      treated for solid malignancy on 39 arms (97%), mainly melanoma (40%). Two arms
      included ICI combinations. The incidence of any grade irAE was higher in patients
      who received ICI targeting CTLA-4 (53.8%) than PD-1 (26.5%) and PD-L1 ICI (17.1%)
      (P<0.001). Comparative specific irAE rates were calculated for each ICI target.
      CONCLUSIONS: Our systematic review supported our mechanistic-driven hypothesis.
      We encourage investigators to report the incidence of irAE in future ICI
      combination trials.

PMID- 29065980
TI  - Genistein: Its role in metabolic diseases and cancer.
AB  - Genistein is an isoflavone present in soy and is known to have multiple molecular
      effects, such as the inhibition of inflammation, promotion of apoptosis, and
      modulation of steroidal hormone receptors and metabolic pathways. Since these
      molecular effects impact carcinogenesis, cancer propagation, obesity,
      osteoporosis, and metabolic syndromes, genistein plays an important role in
      preventing and treating common disorders. The role of genistein has not been
      adequately evaluated in all these clinical settings. This review summarizes some
      of the known molecular effects of genistein and its potential role in health
      maintenance and treatment.

PMID- 29065981
TI  - Complexity of the genomic landscape of renal cell carcinoma: Implications for
      targeted therapy and precision immuno-oncology.
AB  - The topic of tumoral heterogeneity at the genetic level has become relevant in
      various solid origin tumors, particularly in an age of targeted treatment. Renal
      cell carcinoma is known for a sizable subset of tumors presenting at advanced
      clinical stage, further highlighting the importance and timeliness of this topic
      and its potential impact on adjuvant therapy. Recent studies have shown that
      molecular aberrations in renal cell carcinoma go beyond known truncal mutations
      and that downstream, subclonal aberrations are spatially heterogenous.
      Intratumoral heterogeneity as well as the differences in the molecular landscape
      between primary and metastatic lesions remains underappreciated, often due to
      inadequate sampling of tumors. The overall effect of these factors on the
      efficacy of current treatment options in renal cell carcinoma remains unknown;
      however, several recent studies have attempted to elucidate the extent and impact
      genetic heterogeneity in renal cell neoplasia may have on patient treatment and
      prognosis.

PMID- 29065982
TI  - Corrigendum to "The vicious circle of treatment-induced toxicities in locally
      advanced head and neck cancer and the impact on treatment intensity" [Crit. Rev.
      Oncol./Hematol. 116 (2017) 82-88].

PMID- 29065983
TI  - Combination immunotherapy strategies in advanced non-small cell lung cancer
      (NSCLC): Does biological rationale meet clinical needs?
AB  - Immune checkpoint inhibitors (ICIs) have emerged as one of the main new
      therapeutic options for advanced non-small cell lung cancer (NSCLC) patients.
      Even though they demonstrated superiority towards standard chemotherapy in
      different disease settings, the response rates do not exceed 45% in highly
      molecularly selected patients. This is related to known limitations of the
      available biomarkers, as well to the complex and dynamic nature of tumor
      microenvironment. The study of the different strategies adopted by tumor cells to
      escape the immune system lays the basis of the new combination strategies. This
      review focuses on analyzing the biological rationale and early clinical data
      available concerning therapeutic strategies combining ICIs together, ICIs with
      different regimens and schedules of standard chemotherapy, ICIs with tyrosine
      kinase inhibitors, ICIs with antiangiogenic agents and ICs with radiotherapy.

PMID- 29065985
TI  - Hand-foot skin reaction with vascular endothelial growth factor receptor tyrosine
      kinase inhibitors in cancer patients: A systematic review and meta-analysis.
AB  - A meta-analysis was conducted to systematically review the risk of hand-foot skin
      reaction (HFSR) with vascular endothelial growth factor receptor tyrosine kinase
      inhibitors (VEGFR-TKIs) in patients with cancer. The relevant studies of the
      randomized controlled trials (RCTs) in cancer patients treated with VEGFR-TKIs
      were retrieved and the systematic evaluation was conducted. EMBASE, MEDLINE, and
      PubMed were searched for articles published till May 2017. Twenty-one RCTs and
      9552 patients were included. The current analysis suggested that the use of VEGFR
      TKIs increased the risk of all-grade HFSR (7.04;95%CI, 5.33-9.30;p<0.00001) and
      high-grade (>=grade 3) HFSR (21.62;95%CI, 15.19-30.78;p<0.00001). On subgroup
      analyses, the risk ratio (RR) of all-grade HFSR varies significantly according to
      cancer type, whereas the RR of high-grade HFSR did not. The risk of all-grade and
      high-grade HFSR did not affect by drug types, treatment line, median age and
      treatment duration.

PMID- 29065984
TI  - Systematic literature review of health-related quality of life in locally
      advanced non-small cell lung cancer: Has it yet become state-of-the-art?
AB  - Lung cancer and its treatment have an important impact on the patients' health
      related quality-of-life (HRQoL). A systematic literature review of prospective
      clinical studies published since 2005 and measuring HRQoL in patients with
      locally-advanced non-small cell lung cancer (LA- NSCLC) was performed. Besides
      reviewing the HRQoL impact of LA-NSCLC treatment, it critically examined the
      frequency, methodology and quality of HRQoL data collection and analysis in LA
      NSCLC clinical studies. Out of 814 potentially eligible publications, only 27
      (representing 19 individual studies) met the inclusion criteria. Eight studies
      documented an impact on HRQoL. Large variability in use of HRQoL instruments,
      statistical analysis and methodological quality was observed. Reporting of HRQoL
      data lacks standardization, but recent initiatives establishing recommendations
      to standardize the analysis and reporting of HRQoL in cancer trials are expected
      to address these issues. Overall, more research is needed to evaluate the
      treatment impact on HRQoL in both clinical trials and daily care.

PMID- 29065994
TI  - Climate change, hurricanes and public health.

PMID- 29065986
TI  - Critical risk-benefit assessment of the novel anti-cancer aurora a kinase
      inhibitor alisertib (MLN8237): A comprehensive review of the clinical data.
AB  - BACKGROUND: Many current anticancer chemotherapeutics suffer from significant
      side effects, which have led to the exploration of more targeted therapies. This
      resulted in the exploration of inhibitors of Aurora A kinase as a potential anti
      cancer treatment. Alisertib (MLN8237) has proven to be a potent Aurora A kinase
      inhibitor that had the highest safety profile among its therapeutic family. Phase
      I/II/III clinical trials with Alisertib have been carried out and reported
      promising efficacy, yet serious side effects. This article attempts to assess the
      clinical effect of Alisertib administration in various cancer phenotypes while
      describing the reported side effects. METHODS: Alisertib clinical data were
      systematically retrieved from Medline, CINAHL, PubMed, and Cochrane Central
      Register of Controlled Trials and analyzed for quality, relevance, and
      originality in three stages prior to inclusion. RESULTS: Overall, seven studies
      met inclusion criteria and enrolled a total of 630 patients. The reported
      "potential" clinical effect of Alisertib in various tumours is promising as it
      improved time to disease progression, progression-free survival, and the duration
      of disease stability. The achieved improvement therefore rationalizes its further
      investigation as a novel anticancer therapy. However, the administration of the
      drug was associated with serious haematological disturbances in a relatively high
      percentage of patients. CONCLUSION: The evidence of the anti-tumour effect of
      Alisertib administration is compelling in various types of malignancies. The
      reported side effects were serious but manageable in many cases. Topical or more
      targeted routes of administration are suggested when possible to overcome off
      target events with systematic administration of the drug.

PMID- 29065995
TI  - Mental flexibility: An MEG investigation in typically developing children.
AB  - Mental flexibility is a core property of cognitive executive functions, relying
      on an extended frontoparietal network in the brain. fMRI research comparing
      typically developing children and adults has found that children from an early
      age recruit the same "classic" brain areas associated with mental flexibility as
      adults; however, there is evidence that the timing of activation may be
      different. To investigate the temporal dynamics of brain activity associated with
      mental flexibility in children, we recruited 22 typically developing children (8
      15 years) to complete a set-shifting task in the MEG. Our results showed that
      while the children relied on the same frontoparietal network of mental
      flexibility, there was a different emphasis on active brain regions, with
      children preferentially using their posterior parietal cortices. Additional areas
      such as the temporal pole and the premotor areas were also recruited, potentially
      playing a supporting role. Although children shared the same window of peak
      activity as adults, 75-350ms, we found a significant decrease in activation
      latency with increasing age, suggesting the presence of developmental differences
      in timing of brain activity in areas supporting mental flexibility during
      childhood.

PMID- 29065996
TI  - Joint Opinion Paper- "Ageing and sexual health'' by the European Board & College
      of Obstetrics and Gynaecology (EBCOG) and the European Menopause and Andropause
      Society (EMAS).

PMID- 29065998
TI  - A regional optimization model for waste-to-energy generation using agricultural
      vegetative residuals.
AB  - The spatial distribution of vegetative agricultural residuals (VAR) implies that
      any waste treatment system (WTS) designed to manage VAR is particularly sensitive
      to transportation costs. Additionally, a wide range of treatment technologies is
      potentially available for VAR treatment, but some of them lack a well-developed
      market for their output products. This study develops a method to design an
      economically feasible VAR treatment system, analyzing the profitability of the
      system as a function of logistics and uncertain market prices of the available
      treatment technologies' products. The design method includes an economic
      optimization model followed by a sensitivity analysis of the potential changes in
      the system's profitability. The results show that the market price of the
      treatment technologies' products has a larger impact on the system's
      profitability than transportation costs. Specifically, if biochar prices reach
      the level forecasted by experts, pyrolysis will become the dominant technology of
      the WTS. The research highlights the importance of the treatment technology
      selection and the location of treatment facilities in the design of an optimal
      WTS for VAR.

PMID- 29065997
TI  - Light-emitting diode 585nm photomodulation inhibiting melanin synthesis and
      inducing autophagy in human melanocytes.
AB  - BACKGROUND: Melasma is a common hyperpigmentation skin disease on face. Light
      emitting diode (LED) photomodulation (585nm) is reported to be effective for the
      treatment of melasma. However, whether and how LED photomodulation would
      influence melanogenesis of human epidermal melanocytes (HEMs) is unknown.
      OBJECTIVE: To evaluate the effects of LED photomodulation (585nm) on
      melanogenesis in HEMs. METHODS: HEMs were irradiated with fluences of 0, 5, 10
      and 20J/cm2 585nm LED light. After 5-day treatment, cell viability was analyzed
      by CCK-8 assay, and apoptosis was assessed by Annexin V APC assay. Melanin
      content and tyrosinase activity were measured by spectrophotometer. Melanosome
      stage and autophagosomes were determined under transmission electron microscope
      (TEM). The formation of autophagic punctate structures was observed under
      confocal microscope. RT-PCR and western blotting were used to assess the
      expression of relative mRNA and protein levels. RESULTS: Yellow light LED 585nm
      had no effects on HEMs cell viability and apoptosis. Treatment with LED 585nm
      from 5J/cm2 to 20J/cm2 inhibited melanosome maturation, decreased melanin content
      and tyrosinase activity. Inhibition was accompanied by the decreased expression
      of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1) and microphthalmia
      associated transcription factor (MITF) on both mRNA and protein levels.
      Autophagosomes were observed under TEM. Autophagic punctate structures of
      microtubule-associated protein light chain 3 (LC3) proteins were induced by LED
      585nm light. The configuration change of LC3 from LC3-I to LC3-II, and the
      degradation of p62 protein were observed after LED 585nm. Furthermore, we also
      revealed that the anti-melanogenic effect of LED 585nm photomodulation was
      reversed by 3-Methyladenine (3-MA), which inhibits autophagy by blocking
      autophagosome formation via the inhibition of type III Phosphatidylinositol 3
      kinases (PI-3K). CONCLUSIONS: Our finding demonstrated that LED photomodulation
      with 585nm wavelength suppressed melanin content in HEMs, and the effect was
      caused by its dose-dependent inhibition on melanogenesis and the induction of
      HEMs autophagy. This may provide new insights into the efficacy of LED
      photomodulation in the treatment of hyperpigmentation disorders.

PMID- 29065999
TI  - Editorial.

PMID- 29066000
TI  - Platelet-rich plasma for the therapeutic management of temporomandibular joint
      disorders: a systematic review.
AB  - This systematic review aimed to investigate whether intra-articular injections of
      platelet-rich plasma (PRP) are beneficial for the treatment of degenerative
      temporomandibular disorders, such as temporomandibular joint osteoarthritis (TMJ
      OA) and disc displacement with osteoarthritic lesions, when compared to other
      treatments, such as injections of hyaluronic acid (HA) or saline. An electronic
      search of the MEDLINE and Scopus databases was performed using combinations of
      the terms "temporomandibular" and "platelet rich plasma", to identify studies
      reported in English and published up until May 2017. A hand-search of relevant
      journals and the reference lists of selected articles was also performed. The
      initial screening identified 153 records, of which only six fulfilled the
      inclusion criteria and were included in this review. Of these studies, three
      compared PRP with HA, while three compared PRP with Ringer's lactate or saline.
      Four of the studies found PRP injections to be superior in terms of improvements
      in mandibular range of motion and pain intensity up to 12 months after treatment,
      while the remaining two studies found similar results for the different
      treatments. There is slight evidence for the potential benefits of intra
      articular injections of PRP in patients with TMJ-OA. However, a standardized
      protocol for PRP preparation and application needs to be established.

PMID- 29066001
TI  - Antiproliferative and proapoptotic activity of molecular copper(II) complex of N
      1-tosylcytosine.
AB  - In an attempt to enhance the previously observed antiproliferative capacity of 1
      (p-toluenesulfonyl)cytosine (N-1-tosylcytosine, ligand 1), its copper(II) complex
      (Cu(1-TsC-N3)2Cl2, complex 2) was prepared and tested in vitro on various
      carcinoma and leukemia cells. The comparative in vitro studies using the ligand
      1, the complex 2, CuCl2x2H2O salt (salt 3) and the 1:2 mixture of the salt 3 and
      ligand 1 (mixture 4) were performed on normal (WI38), human carcinoma (HeLa,
      CaCo2, MiaPaCa2, SW620), lymphoma (Raji) and leukemia (K562) cell lines.
      Significantly elevated concentration of the intracellular copper after treatment
      of K562 cells and HeLa cells during 2h with complex 2 (7.83 vs. 5.4 times) was
      detected by atomic absorption spectroscopy. Cytotoxicity was analyzed by MTT
      assay. We found that antiproliferative capacity of the tested compounds varies
      (IC50 after 72h of exposure: 0.6*10-6M to>100*10-6M). Leukemia and lymphoma cells
      were found the most sensitive to complex 2 which showed more than 100 times
      higher in vitro activity against K562 cells than ligand 1. Apoptotic
      morphological changes, an externalization of phosphatydilserine, and changes in
      the mitochondrial membrane potential of treated cells were found. The caspase-3
      activity in HeLa and K562 cells was measured by caspase-3 colorimetric assay kit.
      Caspase-3 was not activated in the treated K562 cells while salt 3 and the
      mixture 4 in the HeLa cells significantly increased tested enzyme activity. These
      findings suggest that copper(II) in the molecular complex 2 by improving entry of
      the N-1-tosylcytosine 1 into cells increases its antiproliferative capacity. In
      summary, the present study demonstrated that complex 2 possesses an antileukemic
      effect on K562 cells, and its anticancer activity was attributed with induction
      of apoptosis. The exact mechanism of apoptosis induction by complex 2 must be
      further investigated.

PMID- 29066002
TI  - Pediatric traumatic brain injury at Mbarara Regional Referral Hospital, Uganda.
AB  - BACKGROUND: In Uganda, TBI constitute the majority of neurosurgical admissions
      and deaths specially in the pediatric population. This study aims to determine
      the factors associated with poor outcome among pediatric TBI cases at a major
      referral hospital in western Uganda. METHODS: This study was conducted at Mbarara
      Regional Referral Hospital (MRRH) in western Uganda. All pediatric neurosurgical
      cases between 2012 and 2015 were reviewed. In-hospital mortality and discharge
      GCS were the main outcomes of interest. Multivariable logistic regression with
      backward elimination was used to determine the factors significantly associated
      with outcome. RESULTS: A total of 381 pediatric TBI patients were admitted to
      MRRH between 2012 and 2015. The mean age was 8.6 (SD 5.6) with a male
      predominance (62.0%). The most common mechanism of injury overall was RTI, which
      was responsible for 71% of all TBI cases. In the multivariable logistic
      regression model, admission GCS < 13 was a strong predictor of poor outcome and
      in-hospital mortality compared to admission GCS >= 13, with patients
      demonstrating an odds ratio of 30 (95%CI: 7-132) and OR of 18 (95%CI: 4-79),
      respectively. CONCLUSION: Given the lack of published literature on pediatric TBI
      in LMICs, this study was the first to describe and evaluate risk factors
      associated with TBI severity among pediatric patients at a major referral
      hospital in western Uganda. Injury severity on admission was the only variable
      found to be significantly associated with discharge outcome. This study
      ultimately highlights the need for more effective preventative measures to
      decrease admission severity.

PMID- 29066003
TI  - Clinical outcomes after burns in elderly patients over 70 years: A 17-year
      retrospective analysis.
AB  - INTRODUCTION: In the United Stated population >70years is likely to double by the
      year 2050. Elderly population (>70years) are most vulnerable to burns and
      outcomes following such injuries in this special group is poorly studied. This
      study aimed to look at outcomes following burns in patients >70years over a
      period of 17 years. MATERIALS AND METHODS: Data on 6512 patients admitted to a
      Level I Burn Center between 1995 and 2011 was analyzed. Age, gender, ethnicity,
      TBSA, burn etiology, hospital and burn intensive care unit (ICU) length of stay
      (LOS) and status at discharge were abstracted. Three broad categories were
      created based on presence or absence of smoke inhalation, No smoke inhalation
      (Group A), smoke inhalation only (Group B) and smoke inhalation with burn injury
      (Group C). Differences were analyzed using the student's t-test for continuous
      variables and Chi-Square test for categorical variables. RESULTS: The study group
      was comprised of 564 patients, 72.3% in group A, 4.8% in group B and 22.9% in
      group C formed the study population. The mean age of the patients studied was
      80.4+/-6.7, with female patients being more common (58%). The number of
      Caucasians (72.9%) was highest in group C compared to other racial groups
      (p=0.047). Majority of patients in the group B (59.3%) were admitted directly
      compared to other two groups (group A=24.0%, group B=34.9%, p<0.001). Overall
      percent total body surface area (% TBSA) and % TBSA third degree burns were
      higher in group C, whereas % TBSA second degree burns were common in group B
      (p<0.05). The number ICU admissions, the mean length of ICU stay, mean duration
      of ventilator support and mean length of hospitalization were all highest in
      group C patients (p<0.001). The number of discharges to home without home health
      aide were higher in group A, whereas the number of discharges to nursing
      home/rehabilitation/extended care facility were higher in group B (p<0.001). The
      in-hospital mortality (58.1%, p<0.001) and overall burn related mortality (62.8%,
      p<0.001) were highest in group C. There was no significant difference between the
      groups for the number of patients converted to hospice care (p=0.21). On
      multivariate analysis ICU admission (Odds Ratio [OR]=3.7, 95% Confidence Interval
      [95% CI]=2.1-6.5), ventilator support (OR=7.1, 95% CI=4.1-12.0), and %TBSA >10%
      (OR=3.1, 95% CI=1.9-5.0) significantly increased mortality. In terms of
      complications, group C had a significantly higher incidence of pneumonia (18.6%,
      p<0.001), respiratory failure (17.1%, p=0.001), and sepsis (7.8%, p=0.003).
      CONCLUSIONS: Patients >70 years constitute small (8.6%) but significant number
      among burn patients. The overall ICU admissions, number of days on ventilator,
      ICU stay, in-hospital mortality and overall mortality is higher in this group of
      population even for low % TBSA burns. Presence of smoke inhalation increases
      mortality.

PMID- 29066004
TI  - Microstructural white matter abnormalities in patients with COL6A3 mutations
      (DYT27 dystonia).
AB  - INTRODUCTION: Recently, mutations in the collagen gene COL6A3 have been reported
      in patients with autosomal-recessive, isolated dystonia (DYT27). Zebrafish models
      of COL6A3 mutations showed deficits in axonal targeting mechanisms. Therefore,
      COL6A3 mutations have been considered to contribute to irregular sensorimotor
      circuit formation. To test this hypothesis, we examined structural abnormalities
      in cerebral fiber tracts of dystonia patients with COL6A3 mutations using
      diffusion tensor imaging. METHODS: We performed a voxel-wise statistical analysis
      to compare fractional anisotropy within whole-brain white matter in four of the
      previously reported dystonia patients with COL6A3 mutations and 12 healthy
      controls. Region of interests-based probabilistic tractography was performed as a
      post-hoc-analysis. RESULTS: Dystonia patients with COL6A3 mutations showed
      significantly decreased fractional anisotropy bilaterally in midbrain, pons,
      cerebellar peduncles, thalamus, internal capsule and in frontal and parietal
      subcortical regions compared to healthy controls. Tractography revealed a
      decreased fractional anisotropy in patients with COL6A3-associated dystonia
      between bilateral dentate nucleus and thalamus. CONCLUSION: Diffusion tensor
      imaging demonstrates an altered white matter structure especially in various
      parts of the cerebello-thalamo-cortical network in dystonia patients with COL6A3
      mutations. This suggests that COL6A3 mutations could contribute to abnormal
      circuit formation as potential basis of dystonia.

PMID- 29066005
TI  - The Endovenous Literature: A Perfect Storm of Limited Effectiveness Data, Rapid
      Technological Evolution and Potential Conflict of Interest.

PMID- 29066006
TI  - A Huge Thoracic Aortic Aneurysm.

PMID- 29066007
TI  - Point shear-wave elastography in chronic pancreatitis: A promising tool for
      staging disease severity.
AB  - BACKGROUND: Objectives: ElastPQ(r)-pSWE is an ultrasound technique developed to
      stage disease severity in patients with chronic liver diseases. Little data is
      available about its application to the pancreas. We aimed to assess the
      feasibility and reproducibility of pancreatic stiffness (PS) measurements in
      patients with chronic pancreatitis and their relationship with clinical and
      laboratory data. MATERIAL AND METHODS: 52 consecutive patients with chronic
      pancreatitis (CP) (40 males; median age 60 years) underwent hepatic and
      pancreatic pSWE. Liver stiffness was measured by transient elastography, 42
      healthy subjects being controls (25 males; median age 54 years). Pancreatic pSWE
      inter-observer agreement was analyzed by intraclass correlation coefficient
      (ICC). The effects of clinical, laboratory and US data on PS measurements were
      evaluated by linear regression. RESULTS: pSWE was feasible in all the CP
      patients, but one. Pancreatic stiffness was significantly higher in CP patients
      than healthy controls (4.3 +/- SD 2.4 vs. 2.8 +/- SD 1.1 kPa, respectively, p =
      0.001). Significantly higher values in the CP group were observed in patients
      with longer disease duration (>10 vs. <=10 years) (5.8 +/- SD 4 vs. 3.9 +/- SD
      1.5 kPa, respectively, p = 0.01), on chronic analgesic drugs (6.0 vs. 3.5 kPa, p
      < 0.05) and with lower body weight (p < 0.05, r = -0.38). At multivariate
      analysis all the three variables resulted independently associated to the
      pancreatic stiffness value. The ICC for PS was 0.77. CONCLUSIONS: ElastPQ(r)-pSWE
      is promising and reproducible in assessing pancreatic stiffness, which mainly
      reflects disease length and severity. Accordingly, its use is of potential value
      in stratifying CP patients by identifying those with a more serious degree of
      disease.

PMID- 29066008
TI  - 49th SIOP Congress.

PMID- 29066009
TI  - Rising cancer drug costs in the USA.

PMID- 29066010
TI  - UK radiologist staffing crisis reaches critical levels.

PMID- 29066011
TI  - Socioeconomic Equity in the Receipt of In-Hospital Care and Outcomes in
      Australian Acute Coronary Syndrome Patients: The CONCORDANCE Registry.
AB  - BACKGROUND: Socioeconomic status (SES) is a social determinant of both health and
      receipt of health care services, but its impact is under-studied in acute
      coronary syndrome (ACS). The aim of this study was to examine the influence of
      SES on in-hospital care, and clinical events for patients presenting with an ACS
      to public hospitals in Australia. METHODS: Data from 9064 ACS patient records
      were collected from 41 public hospitals nationwide from 2009 as part of the
      Cooperative National Registry of Acute Coronary Syndrome Care (CONCORDANCE)
      registry. For this analysis, we divided the cohort into four socioeconomic groups
      (based on postcode of usual residence) and compared the in-hospital care provided
      and clinical outcomes before and after adjustment for both patient clinical
      characteristics and hospital clustering. RESULTS: Patients were divided into four
      SES groups (from the most to the least disadvantaged: 2042 (23%) vs. 2104 (23%)
      vs. 1994 (22%) vs. 2968 (32%)). Following adjustments for patient
      characteristics, there were no differences in the odds of receiving coronary
      angiogram, revascularisation, prescription of recommended medication, or referral
      to cardiac rehabilitation across the SES groups (p=0.06, 0.69, 0.89 and 0.79,
      respectively). After adjustment for clinical characteristics, no associations
      were observed for in-hospital and cumulative death (p=0.62 and p=0.71,
      respectively). However, the most disadvantaged group were 37% more likely to have
      a major adverse cardiovascular event (MACE) than the least disadvantaged group
      (OR (95% CI): 1.37 (1.1, 1.71), p=0.02) driven by incidence of in-hospital heart
      failure. CONCLUSIONS: Although there may be gaps in the delivery of care, this
      delivery of care does not differ by patient's SES. It is an encouraging
      affirmation that all patients in Australian public hospitals receive equal in
      hospital care, and the likelihood of death is comparable between the SES groups.

PMID- 29066012
TI  - Ultrasound in polyneuropathies - Is size or structure all that matters?

PMID- 29066015
TI  - Prolapsus du cordon a la suite d'une rupture prematuree des membranes.

PMID- 29066014
TI  - Up-regulation of miR-181a in clear cell renal cell carcinoma is associated with
      lower KLF6 expression, enhanced cell proliferation, accelerated cell cycle
      transition, and diminished apoptosis.
AB  - OBJECTIVES: Dysregulated expression of miR-181a accompanies tumorigenesis in many
      human cancers. However, in clear cell renal cell carcinoma (ccRCC), the role of
      miR-181a remains unclear. The aim of this study was to investigate biological
      functions of miR-181a and its expression levels in ccRCC tissues and cancer cell
      lines. MATERIAL AND METHODS: Expression levels of miR-181a in samples of ccRCC
      tumors and adjacent nontumor tissues from 42 patients as well as in 786-O, 769-P,
      A498, and CAKI-1 ccRCC cell lines were determined by quantitative real-time
      polymerase chain reaction. Potential targets of miR-181a were predicted using
      bioinformatic approaches and then verified by using the luciferase reporter
      assay. The effects of miR-181a on cell proliferation, colony formation, cell
      cycle progression, and apoptosis were investigated in ccRCC cell lines
      transfected with specific miR-181a mimic and inhibitor. RESULTS: We found that
      miR-181a expression was up-regulated in ccRCC tissues and cell lines. The
      expression level of miR-181a significantly correlated with the tumor size,
      tumor/node/metastasis staging, and Fuhrman grade. Luciferase assays showed that
      KLF6 was a target of miR-181a. KLF6 expression was inversely correlated with the
      level of miR-181a. Overexpression of miR-181a led to reduced KLF6 mRNA and
      protein levels, whereas mutations of the potential miR-181a binding sites in the
      KLF6 gene abrogated this inhibitory effect. Furthermore, overexpression of miR
      181a promoted proliferation and G1/S cell cycle transition, as well as inhibited
      apoptosis by down-regulating KLF6 in ccRCC cells. CONCLUSIONS: miR-181a is up
      regulated in ccRCC and may act as a tumor promoting factor by targeting KLF6
      expression. Manipulating miR-181a may provide a beneficial effect in the
      treatment of ccRCC.

PMID- 29066013
TI  - Role of surgical approach on lymph node dissection yield and survival in patients
      with upper tract urothelial carcinoma.
AB  - OBJECTIVES: With increasing utilization of robot-assisted surgery in urologic
      oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of
      choice for patients with upper tract urothelial carcinoma (UTUC). The role of
      surgical approach on lymph node dissection (LND) and lymph node (LN) yield is
      unclear, and potential therapeutic effects are unknown. Here we analyze the
      effects of surgical approach on LN yield, performance of LND, and overall
      survival (OS). METHODS AND MATERIALS: Patients with UTUC who underwent
      nephroureterectomy from 2010 to 2013 were identified in the National Cancer
      Database. Outcomes of interest included rate of LND, LN yield, and OS. Logistic
      regression analyses were used to predict performance of LND. Negative binomial
      regression was used to derive incidence rate ratios for LN yield. Cox
      proportional hazards models were used to quantify survival outcomes. RESULTS: A
      total of 3,116 patients met inclusion criteria. LND was performed in 41%
      (314/762) of RNU, 27% (380/1385) of LNU cases, and 35% (340/969) of ONU
      (P<0.001). Compared with an ONU, patients who underwent a LNU had significantly
      lower odds of receiving a LND (OR = 0.70, 95% CI: 0.55-0.87) and had fewer LNs
      removed (IRR = 0.69, 95% CI: 0.60-0.80), while RNU trended toward increased LN
      yield (IRR = 1.14, 95% CI: 0.98-1.33). In a Cox proportional hazards model,
      increasing LN yield was associated with improved OS in patients with pN0 disease
      (HR = 0.97 per 1 unit increase in LN yield, 95% CI: 0.95-0.99). CONCLUSIONS:
      Compared with an ONU, RNU does not compromise performance of a LND and may be
      associated with improved LN yield. LNU is associated with the lowest rates of LND
      and LN yield. Increasing LN yield is associated with improved OS in patients with
      pN0 disease. Despite differential rates of LND and LN yield, surgical approach
      did not independently affect OS.

PMID- 29066016
TI  - The Impact of Access Barriers on Fertility Treatment Decision Making: A
      Qualitative Study From the Perspectives of Patients and Service Providers.
AB  - OBJECTIVE: The purpose of this study was to explore how barriers to accessing
      fertility services affect the treatment decisions made by fertility patients and
      service providers in Newfoundland and Labrador. METHODS: Semistructured, in-depth
      interviews were conducted with 11 patients across Newfoundland and with eight
      service providers from Newfoundland and Labrador Fertility Services (located in
      St. John's) to gather the perspectives of both patients and providers. The
      interview transcripts were analyzed thematically. RESULTS: Patients' responses to
      fertility service access barriers included choosing cheaper drugs, substituting
      intrauterine insemination (IUI) for IVF or not using IVF, delaying IVF, choosing
      more accessible IVF clinics, transferring multiple embryos, and stopping
      treatment altogether. Some patients, however, noted that the barriers would not
      stop them from continuing with treatment. Providers' responses to the barriers
      patients faced included changing drug protocols, manipulating ovulation,
      providing teleconsultations, and minimizing patients' clinic visits for those
      living some distance away from St. John's. CONCLUSION: Both patients and
      providers make treatment-related decisions to maximize the likelihood of a
      successful pregnancy and to reduce costs, which can result in less effective care
      and at times increased risk to the patient. Unlike with other types of care,
      responses to barriers to fertility treatment largely result in changes to
      individual patient treatment plans rather than changing models of care. As a
      result, many patients must continue to seek fertility services in large urban
      centres and incur substantial personal costs.

PMID- 29066017
TI  - Cord Prolapse After Preterm Premature Rupture of the Membranes.

PMID- 29066018
TI  - A Practical Approach to Fatigue Management in Colorectal Cancer.
AB  - Cancer-related fatigue is serious and complex, as well as one of the most common
      symptoms experienced by patients with colorectal cancer, with the potential to
      compromise quality of life, activities of daily living, and ultimately survival.
      There is a lack of consensus about the definition of cancer-related fatigue;
      however, definitions have been put forward by the European Association for
      Palliative Care (EAPC) and the National Comprehensive Cancer Network (NCCN).
      Numerous cancer- and treatment-related factors can contribute to fatigue,
      including disease progression, comorbidities, medical complications such as
      anemia, side effects of other medications, and a number of physical and
      psychologic factors. This underlines the importance of tackling factors that may
      contribute to fatigue before reducing the dose of treatment. NCCN guidelines and
      the EAPC have proposed approaches to managing fatigue in cancer patients;
      however, relatively few therapeutic agents have been demonstrated to reduce
      fatigue in randomized controlled trials. It is recognized that physical activity
      produces many beneficial physiologic modifications to markers of physical
      performance that can help to counteract various causes of fatigue. In
      appropriately managed and monitored patients with colorectal cancer, emerging
      evidence indicates that exercise programs may have a favorable influence on
      cancer-related fatigue, quality of life, and clinical outcomes, and therefore may
      help patients tolerate chemotherapy. This review assesses fatigue in patients
      with colorectal cancer and proposes updates to a treatment algorithm that may
      help clinicians manage this common problem.

PMID- 29066019
TI  - Assessment of Coded Excitation Implementation for Estimating Heat-Induced Speed
      of Sound Changes.
AB  - Speed of sound (SoS) is an acoustic property that is highly sensitive to changes
      in tissues. SoS can be mapped non-invasively using ultrasonic through
      transmission wave tomography. This however, practically limits its clinical use
      to the breast. A pulse-echo-based method that has broader clinical use and that
      can reliably measure treatment-induced changes in SoS even under poor signal-to
      noise ratio (SNR) is highly desirable. The aim of this study was to evaluate the
      implementation of coded excitations (CoEs) to improve pulse-echo monitoring of
      heat-induced changes in the SoS. In this study, a binary phase modulated Barker
      sequence and a linear frequency-modulated chirp were compared with a common
      Gaussian pulse transmission. The comparison was conducted using computer
      simulations, as well as transmissions in both agar-gelatin phantoms and ex vivo
      bovine liver. SoS changes were experimentally induced by heating the specimens
      with a therapeutic ultrasound system. The performance of each transmission signal
      was evaluated by correlating the relative echo shifts to the normalized SoS
      measured by through transmission. The computer simulations indicated that CoEs
      are beneficial at very low SNR. The Barker code performed better than both the
      chirp and Gaussian pulses, particularly at SNRs <10 dB (R2 = 0.81 +/- 0.06, 0.68
      +/- 0.07 and 0.55 +/- 0.08, respectively, at 0 dB). At high SNRs, the CoEs
      performed statistically on par with the Gaussian pulse. The experimental findings
      indicated that both Barker and chirp codes performed better than the Gaussian
      pulse on ex vivo liver (R2 = 0.80 +/- 0.15, 0.79 +/- 0.15 and 0.54 +/- 0.17,
      respectively) and comparably on agar-gelatin phantoms. In conclusion, CoEs can be
      beneficial for assessing temperature-induced changes in the SoS using the pulse
      echo method under poor SNR.

PMID- 29066021
TI  - Emergence of antibiotic resistant Shigella species: A matter of concern.
AB  - A major threat to the world is the emergence of antibiotic resistant bacteria,
      which has rendered previously susceptible drugs useless and increased the rate of
      therapeutic failures. Shigella species, which are the causative organism of
      Shigellosis, were earlier susceptible to ampicillin, chloramphenicol, co
      trimoxazole and nalidixic acid but now they have developed resistance against
      fluoroquinolones, cephalosporins and azithromycin. Many shigellosis outbreaks
      have been reported by resistant strains of Shigella species. This review attempts
      to provide a brief overview about the scenario of shigellosis and the emergence
      as well as ubiquitous nature of multidrug resistant (MDR) Shigella species.

PMID- 29066020
TI  - Repeat gram-negative hospital-acquired infections and antibiotic susceptibility:
      A systematic review.
AB  - Repeat HAIs among frequently hospitalized patients may be contributing to the
      high rates of antibiotic resistance seen in gram-negative bacteria (GNB) in
      hospital settings. This systematic review examines the state of the literature
      assessing the association between repeat GNB HAIs and changes in antibiotic
      susceptibility patterns. A systematic search of English language published
      literature was conducted to identify studies in peer-reviewed journals from 2000
      to 2015. Studies must have assessed drug resistance in repeat GNB infections
      longitudinally at the patient level. Two researchers independently reviewed
      search results for papers meeting inclusion criteria and extracted data. Risk of
      bias was assessed using a modified quality assessment tool based on the Checklist
      for Measuring Study Quality and the Quality Assessment Checklist for Cases
      Series. From 3385 articles identified in the search, seven met inclusion
      criteria. Five reported lower antibiotic susceptibility in repeated infections,
      one found a change but did not specify in which direction, and one reported no
      change. All studies were of low to average quality. Despite the dearth of studies
      examining repeat GNB infections, evidence suggests that repeat infections result
      in lower antibiotic susceptibility among hospitalized patients. Larger scale
      studies with strong methodology are warranted.

PMID- 29066022
TI  - Variations in elderly peoples' visits to the emergency departments in Iceland: A
      five-year population study.
AB  - INTRODUCTION: Elderly people visiting emergency departments (ED) are a non
      homogenous group. Gender and other socio-demographic variations in emergency care
      might be present. However, gender-specific ED-data is scarce. METHODS: We
      retrieved retrospective data on all ED-visits, by 67years and older from 2008 to
      2012, and calculated incidence of visits applying population registries. The
      relationship of age-categories, marital status, health and residence with
      outcomes were analyzed descriptively by Chi-square tests. Regression models were
      built to analyze gender-specific variations. RESULTS: Of the total ED-visits, 20%
      were from the elderly population (n=66,141), at a mean 3.1 visits per individual.
      Men (n=30.269) had higher incidence of visits in all age-categories. They were
      mostly married (69%) and women widowed (43%), although the incidence of partnered
      visitors underrepresented population-data while widowed and single living
      overrepresented. Women had more often co-morbidities, their most common causes of
      visits were musculoskeletal (20%) and men circulatory causes (14%). Men were more
      likely to be admitted (OR: 1.23; 95% CI 1.16-1.30) and had more unplanned ED
      revisits (HR: 1.20; 95% CI 1.06-1.35) within 30 days. DISCUSSION: Elderly men
      visiting the ED were more often married than women. Gender differences were found
      in causes of visits and outcomes. In clinical practice, gender may be considered
      when identifying risk and planning adequate care related elderly ED-visits.

PMID- 29066023
TI  - Response of heterogeneous vegetation to aerosol radiative forcing over a
      northeast Indian station.
AB  - Importance of atmospheric aerosols through direct and indirect effects on
      hydrological cycle is highlighted through multiple studies. This study tries to
      find how much the aerosols can affect evapo-transpiration (ET), a key component
      of the hydrological cycle over high NDVI (normalized difference vegetation
      index)/dense canopy, over Dibrugarh, known for vast tea plantation. The radiative
      effects of aerosols are calculated using satellite (Terra-MODIS) and reanalysis
      data on daily and monthly scales. Aerosol optical depth (AOD) obtained from
      satellite and ground observations compares well. Aerosol radiative forcing (ARF),
      calculated using MERRA data sets of 'clean-clear radiation' and 'clear-radiation'
      at the surface, shows a lower forcing efficiency, 35 Wm-zs, that is about half of
      that of ground observations. As vegetation controls ET over high NDVI area to the
      maximum and that gets modified through ARF, a regression equation is fitted
      between ET, AOD and NDVI for this station as ET = 0.25 + (-84.27) * AOD +
      (131.51) * NDVI that explains 82% of 'daily' ET variation using easily available
      satellite data. ET is found to follow net radiation closely and the direct
      relation between soil moisture and ET is weak on daily scale over this station as
      it may be acting through NDVI.

PMID- 29066024
TI  - DNA sequencing and copy number variation analysis of MCHR2 in a cohort of Prader
      Willi like (PWL) patients.
AB  - BACKGROUND: Prader Willi Syndrome (PWS) is a syndromic form of obesity caused by
      a chromosomal aberration on chromosome 15q11.2-q13. Patients with a comparable
      phenotype to PWS not carrying the 15q11.2-q13 defect are classified as Prader
      Willi like (PWL). In literature, PWL patients do frequently harbor deletions at
      6q16, which led to the identification of the single-minded 1 (SIM1) gene as a
      possible cause for the presence of obesity in these patients. However, our
      previous work in a PWL cohort showed a rather limited involvement of SIM1 in the
      obesity phenotype. In this paper, we investigated the causal role of the melanin
      concentrating hormone receptor 2 (MCHR2) gene in PWL patients, as most of the
      reported 6q16 deletions also encompass this gene and it is suggested to be active
      in the control of feeding behavior and energy metabolism. METHODS: Copy number
      variation analysis of the MCHR2 genomic region followed by mutation analysis of
      MCHR2 was performed in a PWL cohort. RESULTS: Genome-wide microarray analysis of
      109 patients with PWL did not show any gene harboring deletions on chromosome
      6q16. Mutation analysis in 92 patients with PWL demonstrated three MCHR2
      variants: p.T47A (c.139A>G), p.A76A (c.228T>C) and c.*16A>G. We identified a
      significantly higher prevalence of the c.228T>C C allele in our PWL cohort
      compared to previously published results and controls of the ExAC Database.
      CONCLUSION: Overall, our results are in line with some previously performed
      studies suggesting that MCHR2 is not a major contributor to human obesity and the
      PWL phenotype.

PMID- 29066025
TI  - Eating alone and metabolic syndrome: A population-based Korean National Health
      and Nutrition Examination Survey 2013-2014.
AB  - Eating alone has been an emerging social concern in modern life. However, there
      is little research on the association between eating alone and Metabolic syndrome
      (MetS). We aimed to assess the association between eating alone and the MetS and
      to identify whether sociodemographic factors modify this association. This study
      included 7725 adults (>=19 years) who participated in the Korean National Health
      and Nutrition Examination Survey (KNHANES) 2013-2014. Multivariable logistic
      regression analysis was used for assessing the association of eating alone (none,
      1 time/day, and >=2 times/day) with MetS. The percentages of subjects with MetS
      were 30.4% in men and 24.2% in women. 20.8% of men and 29.2% of women ate alone
      >=2 times/day. Individuals who ate alone 2 or more times per day showed higher
      frequency of living alone, having no spouse, skip meals, and less eating out
      (p<0.05). Women with eating alone >=2 times/day had a crude OR of 1.29 (95%
      CI:1.08-1.53, p-trend=0.001) for MetS compared with women without eating alone.
      However, this association was no longer significant after adjustments for
      confounding factors. Eating alone >=2 times/day was significantly associated with
      increase abdominal obesity (OR, 95% CI:1.45, 1.10-1.91, p-trend=0.039) and MetS
      (1.64, 1.28-2.10, p-trend=0.004) in men. Eating alone was associated with a
      higher likelihood of having a MetS in men without spouse as compared with those
      with spouse (OR for men without spouse 3.02, 95% CI:1.50-6.11 and OR for men with
      spouse 1.48, 95% CI:1.22-1.7, p-interaction=0.027). Our results indicate that
      eating alone may be a potential risk factor for MetS.

PMID- 29066026
TI  - CD4+CD28+KIR+CD11ahi T cells correlate with disease activity and are
      characterized by a pro-inflammatory epigenetic and transcriptional profile in
      lupus patients.
AB  - OBJECTIVE: The goal of this study was to comprehensively characterize CD4+CD28+ T
      cells overexpressing CD11a and KIR genes, and examine the relationship between
      this T cell subset, genetic risk, and disease activity in lupus. METHODS: The
      size of the CD4+CD28+KIR+CD11ahi T cell subset was determined by flow cytometry,
      and total genetic risk for lupus was calculated in 105 female patients using 43
      confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11ahi T cells were
      isolated from lupus patients or were induced from healthy individuals using 5
      azacytidine. Genome-wide DNA methylation was analyzed using an array-based
      approach, and the transcriptome was assessed by RNA sequencing. Transcripts in
      the CDR3 region were used to assess the TCR repertoire. Chromatin accessibility
      was determined using ATAC-seq. RESULTS: A total of 31,019 differentially
      methylated sites were identified in induced KIR+CD11ahi T cells with >99% being
      hypomethylated. RNA sequencing revealed a clear pro-inflammatory transcriptional
      profile. TCR repertoire analysis suggests less clonotype diversity in KIR+CD11ahi
      compared to autologous KIR-CD11alow T cells. Similarly, primary KIR+CD11ahi T
      cells isolated from lupus patients were hypomethylated and characterized by a pro
      inflammatory chromatin structure. We show that the genetic risk for lupus was
      significantly higher in African-American compared to European-American lupus
      patients. The demethylated CD4+CD28+KIR+CD11ahi T cell subset size was a better
      predictor of disease activity in young (age <= 40) European-American patients
      independent of genetic risk. CONCLUSION: CD4+CD28+KIR+CD11ahi T cells are
      demethylated and characterized by pro-inflammatory epigenetic and transcriptional
      profiles in lupus. Eliminating these cells or blocking their pro-inflammatory
      characteristics might present a novel therapeutic approach for lupus.

PMID- 29066027
TI  - Interferon-beta specific T cells are associated with the development of
      neutralizing antibodies in interferon-beta treated multiple sclerosis patients.
AB  - Beta-interferons are still among the most commonly used drugs to treat Multiple
      Sclerosis (MS). The use of beta-interferons is limited by the development of anti
      drug antibodies (ADA), which may abrogate the treatment effect of the drug.
      Although the antibody response has been well studied, little is known about the T
      cell response to interferon-beta (IFN-beta). We investigated T cell responses in
      four treatment naive MS patients and twenty-three patients treated with IFN-beta
      who had or had not developed ADA to IFN-beta. T cell responses were determined by
      split-well and primary proliferation assays against different IFN-beta protein
      preparations and a set of overlapping peptides covering the full sequence of IFN
      beta. T cell responses to IFN-beta were observed in all donors. ADA positive
      patients showed higher T cell responses to IFN-beta protein than ADA negative
      patients and untreated controls. We identified two immunodominant regions; T cell
      responses to IFN-beta1-40 were observed in all patients independent of ADA
      status, while T cell responses to IFN-beta125-159 were stronger in ADA positive
      than ADA negative patients. IFN-beta specific T cell responses were HLA class II
      restricted and in ADA positive patients skewed towards a Th2 phenotype. In IFN
      beta treated patients we observed a correlation between IFN-beta specific T cell
      responses, serum ADA titer and loss of biological activity of IFN-beta treatment.
      Our studies demonstrate the occurrence of an antigen specific HLA class II
      restricted Th2 T cell response associated with the development of ADA in IFN-beta
      treated patients.

PMID- 29066029
TI  - Antitumor Activity and Safety of Enzalutamide After Abiraterone Acetate: Seeking
      the Optimal Treatment Sequence for Castration-resistant Prostate Cancer Patients.

PMID- 29066028
TI  - Feasibility study of iterative model reconstruction combined with low tube
      voltage, low iodine load, and low iodine delivery rate in craniocervical CT
      angiography.
AB  - AIM: To investigate the feasibility of iterative model reconstruction (IMR)
      combined with low tube voltage, low iodine load, and low iodine deliver rate in
      craniocervical computed tomography angiography (CTA). MATERIALS AND METHODS:
      Sixty patients were randomly divided into two groups (n=30 for each): group A:
      120 kVp, 50 ml of iopromide at a flow rate of 5 ml/s; filtered back projection
      (FBP) reconstruction; group B: 80 kVp, 30 ml of iohexol at 4.5 ml/s; hybrid
      iterative reconstruction (HIR) for group B1 and IMR for group B2. CT attenuation
      values, image noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR),
      subjective image quality, effective dose (ED), iodine load, and iodine delivery
      rate (IDR) were compared. RESULTS: CT attenuation values of the arteries were
      higher in groups B1 and B2 than group A. The SNR and CNR were higher, while image
      noise was lower, for group B2 compared with groups B1 and A. The best subjective
      image quality was obtained with group B2. ED, iodine load, and IDR reduction of
      69.6%, 51.4%, 27%, respectively, was obtained in group B compared with group A.
      CONCLUSION: IMR combined with 80 kVp and 30 ml of iohexol at a flow rate of 4.5
      ml/s for craniocervical CTA can reduce ED, iodine load, and IDR, while improving
      image quality.

PMID- 29066030
TI  - Persistent neglect in everyday life.

PMID- 29066031
TI  - Self-reported bacterial vaginosis and risk of ultrasound-diagnosed incident
      uterine fibroid cases in a prospective cohort study of young African American
      women.

PMID- 29066032
TI  - [Night workers' exposure to harshness factors in France: Lessons learned from the
      2010 SUMER Survey].
AB  - BACKGROUND: Despite the fact that French laws state that night work should be
      exceptional, the number of night workers has sharply increased in the past 20
      years. At the same time, empirical and epidemiological studies indicate that
      night work has negative effects on workers' health. This is why the 2010 French
      pension act considered night work to be a drudgery. The aim of this study is to
      investigate whether night workers are more subject to other factors defined as
      contributing to the drudgery of work than are day workers. This article focuses
      on exposure to physical constraints (manual manipulation of heavy loads, awkward
      posture, exposure to mechanical vibrations) and aggressive physical environment
      (carcinogenic, mutagenic and reprotoxic chemicals [CMR], extreme temperature and
      noise). METHODS: Our study used the 2010 Medical Monitoring Survey of
      Occupational Risks [Surveillance medicale des expositions aux risques
      professionnels, (SUMER)] that was conducted among a sample of around 50,000
      employees representative of 21.7 million French employees. We used logistic
      regressions to explore the potential influence of night work on the probabilities
      of exposure to at least one CMR, noise, thermal nuisance and physical
      constraints. RESULTS: Even though descriptive statistics suggest that night
      workers are more exposed to drudgery of work than day workers, our multivariate
      logistic models indicate that the exposure is not always positively correlated
      with the number of nights worked. Moreover, the exposure differs according to
      gender and socio-occupational category. CONCLUSION: Our findings suggest that
      night workers are more exposed to several factors defined as contributing to the
      drudgery of work than are day workers. Thus, they seem to face multiple
      disadvantages in the labor market. Preventive measures in favor of night workers
      should be targeted at job content as much as work organization.

PMID- 29066033
TI  - [Differentiation of pathogenic leptospires spp by PCR of ligB gene and
      sequencing].
AB  - Leptospirosis is a zoonosis having worldwide distribution. The objective of this
      work was to develop a molecular technique to differentiate pathogenic Leptospira
      spp. A region of adhesin ligB, present only in the pathogenic species was
      amplified by PCR and sequenced. ligBRpet and ligBFpet primers were used, which
      amplified the target DNA from pathogenic L. interrogans reference strains
      serovars Pomona strain Pomona, Canicola strain Hond Utrecht IV, Copenhageni
      strain M 20, Wolffi strain 3705, Pyrogenes strain Salinem, Hardjo strain
      Hardjoprajitmo, L. borgpetersenii serovar Castellonis strain Castellon 3 and 4
      pathogenic strains isolated from bovines, pigs, rats and opossums. L. biflexa
      serovars Patoc strain Patoc I and Andamana strain Andamana were not amplified.
      Sequencing of the amplified products exhibited sufficient variation among
      serovars, which differentiates them.

PMID- 29066034
TI  - Persistence of the same genetic type of Mycoplasma hyopneumoniae in a closed herd
      for at least two years.
AB  - Two cross-sectional studies were carried out in 2013 and 2015 monitoring for
      Mycoplasma hyopneumoniae presence in a swine farm. In these studies, the genetic
      diversity of M. hyopneumoniae was assessed in clinical specimens using a Multiple
      Locus Variable-number tandem repeat Analysis (MLVA) targeting P97 R1, P146 R3 and
      H4 loci. The samples from August 2015 showed the MLVA profile prevalent in June
      2013, therefore it can be concluded that a same genetic type of M. hyopneumoniae
      can persist for at least two years in a closed herd. In addition, the nested PCR
      reactions implemented in this study showed to be useful for MLVA typing in non
      invasive clinical samples.

PMID- 29066035
TI  - Lower limb muscle magnetic resonance imaging in myotonic dystrophy type 1
      correlates with the six-minute walk test and CTG repeats.
AB  - The aim of this study was to elucidate correlations among clinical, genetic, and
      magnetic resonance imaging (MRI) data of muscles in myotonic dystrophy type 1
      (DM1). We retrospectively reviewed the medical records and images of nineteen
      patients with DM1 from different families. We retrieved the genetic data (CTG
      repeats) and the clinical data, which included disease duration, creatine kinase
      level, sum score of manual muscle testing, modified Medical Research Council sum
      score, and the six-minute walk test results (6MWT). The correlation analyses
      showed a statistically significant correlation between the modified Medical
      Research Council sum score and CTG repeat numbers. Among the lower extremity
      muscles, 6MWT correlated most with the sum of the ankle plantar-flexors (the
      soleus, medial, and lateral gastrocnemius muscles). Compared to the other plantar
      flexor muscles, the soleus muscle presented the highest correlation with the
      6MWT. Additionally, our results showed that the CTG repeat numbers did not
      correlate with the 6MWT. However, it correlated with the modified Medical
      Research Council sum score. The ankle plantar-flexor muscles were the most
      severely affected muscles revealed in the whole body MRI, and presented
      statistically significant correlation with the 6MWT. Among the plantar-flexor
      muscles, the soleus muscle most influenced the 6MWT.

PMID- 29066036
TI  - Diagnosis and management of spinal infections.
AB  - The number of spinal infections has been increasing due to aging populations and
      larger numbers of immunocompromised hosts and intravenous drug users. Magnetic
      resonance imaging is a useful tool for the early diagnosis of spinal infections,
      and can yield positive findings just 3-5 days after disease onset. Before
      antibiotic administration, cultures must be initiated from blood and from
      specimens collected from the locus of infection. Based on the pathogens
      identified by culture, appropriate antibiotics should be selected with careful
      consideration of antimicrobial susceptibility and spinal tissue penetration.
      Antibiotic treatment of spinal infections should be continued for longer than for
      most other types of infections, although the optimal duration remains unknown.
      The indications for surgical treatment include progressive neurologic deficits,
      progressive deformity, spinal instability, persistent or recurrent infection, and
      unbearable pain. In most patients with spinal infection, the gold standard
      surgical treatment is anterior radical debridement followed by autologous strut
      bone grafting. The addition of posterior instrumentation has recently become
      popular. This procedure may be performed alone as an alternative surgical option
      in patients in poor condition, and if it dramatically reduces pain, subsequent
      observation may be reasonable. If progressive deformity is observed or pain
      relief is inadequate after posterior instrumentation, additional anterior
      debridement and bone grafting should be scheduled.

PMID- 29066038
TI  - Assessing Responsiveness of Health Systems to Drug Safety Warnings.
AB  - OBJECTIVE: In 2011-2012 the U.S. Food and Drug Administration (FDA) issued safety
      announcements cautioning providers against prescribing high doses of citalopram
      given concerns for QT prolongation. The authors evaluated Veterans Affairs (VA)
      national trends in citalopram use and dose compared with alternative
      antidepressants after the FDA warnings. METHODS: Time series analyses estimated
      the effect of the FDA warnings on citalopram and other antidepressant across
      three periods: before the first FDA warning in August 2011, after the 2011 FDA
      warning until the second warning in March 2012, and after the 2012 FDA warning.
      In a National VA health system, adult VA outpatients prescribed citalopram or
      alternative antidepressants from February 2010 to September 2013 were studied.
      Outpatient use of high-dose citalopram (>40 or >20 mg daily in adults aged > 60
      years) including the proportion of patients prescribed citalopram and difference
      between study periods. RESULTS: Between the first and second FDA warnings, among
      patients aged 18-60, high-dose citalopram use decreased by 2.0% per month (p <
      0.001) and by 1.9% per month (p < 0.001) for older adults. After the second FDA
      warning in 2012, 30.7% of older patients remained on doses higher than the newly
      recommended dose of 20 mg. Reductions in overall use of citalopram were
      accompanied by significant increases in prescriptions of alternative
      antidepressants, with sertraline most widely prescribed. CONCLUSION: Although
      trends in high-dose citalopram use declined after the 2011-2012 FDA warnings,
      roughly one-third of older adults still remained on higher than recommended
      doses. Concomitant increases in sertraline and other antidepressant prescriptions
      suggest potential substitution of these medications for citalopram.

PMID- 29066037
TI  - End-of-Life Care Preferences in Patients with Severe and Persistent Mental
      Illness and Chronic Medical Conditions: A Comparative Cross-Sectional Study.
AB  - OBJECTIVES: Physicians rarely engage severe and persistent mental illness (SPMI)
      patients in end-of-life care discussion despite an increased risk of debilitating
      medical illnesses and mortality. Access to quality palliative care and medical
      assistance in dying (MAID) has become a priority in Canada and many
      jurisdictions. In this study, we compared SPMI and chronic medically ill (CMI)
      patients' end-of-life care preferences and comfort level with end-of-life care
      discussion, and identified potential predictors of interest in MAID. DESIGN:
      Comparative cross-sectional study. SETTING: Hospital-based. PARTICIPANTS: We
      recruited 106 SPMI and 95 CMI patients at the Jewish General Hospital, Canada.
      Patients aged >=40 years, without severe cognitive impairment, able to
      communicate in English or French and provide written informed consent were
      included. MEASUREMENTS: Attitudes towards pain management, palliative sedation,
      MAID, and artificial life support were collected with the Health Care Preferences
      Questionnaire. Adjusted odd ratios (aOR) were calculated for each end-of-life
      care intervention. Comfort with discussion was rated on a Likert scale. A
      stepwise regression analysis was performed to identify predictors of interest in
      MAID. RESULTS: SPMI was not correlated to any end-of-life care intervention,
      except for MAID where SPMI patients were less likely to support its use (aOR:
      0.48, 95% CI: 0.25-0.94, p = 0.03). Religiosity was also correlated with interest
      in MAID (aOR: 0.14, 95% CI: 0.06-0.31, p < 0.001). Patients in both groups were
      comfortable talking about end-of-life care. CONCLUSIONS: SPMI patients are able
      to voice their end-of-life care preferences, and contrary to some fears, do not
      want MAID more than CMI patients.

PMID- 29066039
TI  - Custom-milled individual allogeneic bone grafts for alveolar cleft osteoplasty-A
      technical note.
AB  - INTRODUCTION: Bone grafts from the iliac crest are most commonly used for
      osteoplasties of the cleft alveolus. To preclude undue donoresite morbidity
      custom-milled allogeneic bone grafts might be an appropriate choice. MATERIAL AND
      METHODS: This technical note showcases the repair of an alveolar cleft using an
      individualized allogeneic bone graft in a 36-year old female patient. She was
      asking for an alternative to the iliac crest bone grafting. Her alveolus was
      successfully build up by a custom-milled cancellous bone block allograft
      (maxgraft(r) 80 bonebuilder). RESULTS: Custom-milled cancellous bone block
      allografts can greatly facilitate alveolar cleft repair and may present an
      effective treatment option under the premise that resorption resistance
      corresponds to autografts. CONCLUSION: Further clinical studies are needed to
      explore the potential of bone block allografts for alveolar cleft osteoplasty.

PMID- 29066041
TI  - Accuracy of virtual surgical planning of orthognathic surgery with aid of CAD/CAM
      fabricated surgical splint-A novel 3D analyzing algorithm.
AB  - The benefit of computer-assisted planning in orthognathic surgery has been
      extensively documented over the last decade. This study aims to evaluate the
      accuracy of a virtual orthognathic surgical plan by a novel three dimensional
      (3D) analysis method. Ten patients who required orthognathic surgery were
      included in this study. A virtual surgical plan was achieved by the combination
      of a 3D skull model acquired from computed tomography (CT) and surface scanning
      of the upper and lower dental arch respectively and final occlusal position.
      Osteotomies and movement of maxilla and mandible were simulated by Dolphin
      Imaging 11.8 Premium(r) (Dolphin Imaging and Management Solutions, Chatsworth,
      CA). The surgical plan was transferred to surgical splints fabricated by means of
      Computer Aided Design/Computer Aided Manufacturing (CAD/CAM). Differences of
      three dimensional measurements between the virtual surgical plan and
      postoperative results were evaluated. The results from all parameters showed that
      the virtual surgical plans were successfully transferred by the assistance of
      CAD/CAM fabricated surgical splint. Wilcoxon's signed rank test showed that no
      statistically significant deviation between surgical plan and post-operational
      result could be detected. However, deviation of angle U1 axis-HP and distance of
      A-CP could not fulfill the clinical success criteria. Virtual surgical planning
      and CAD/CAM fabricated surgical splint are proven to facilitate treatment
      planning and offer an accurate surgical result in orthognathic surgery.

PMID- 29066040
TI  - The value of three-dimensional photogrammetry in isolated sagittal synostosis:
      Impact of age and surgical technique on intracranial volume and cephalic index?a
      retrospective cohort study.
AB  - PURPOSE: The aim of this study was to compare the outcome of intracranial volume
      (ICV) and cephalic index (CI) between two different techniques for surgical
      therapy of sagittal synostosis. MATERIAL AND METHODS: Between 2011 and 2015, all
      patients scheduled for surgical therapy of sagittal synostosis were consecutively
      enrolled. All patients younger than 6 months underwent early extended strip
      craniectomy (ESC group), and patients older than 6 months underwent late modified
      pi-procedure (MPP group). To measure ICV and CI, data acquisition was performed
      via three-dimensional photogrammetry, 1 day before (T0) and between 10 and 12
      weeks after surgery (T1). Results were compared with an age-matched reference
      group of healthy children. Perioperative parameters, as duration of surgery and
      the amount of blood loss of both surgical procedures were analyzed. RESULTS: A
      total of 85 patients were enrolled. Of the patients, 48 underwent an extended
      strip craniotomy with parietal osteotomies and biparietal widening and 37
      patients underwent a late modified pi-procedure. There was no significant
      difference between the ESC group and the MPP group regarding the efficacy of
      improving CI (p > 0.05). Both techniques were able to normalize CI and to improve
      head shape. ICV was normal compared to age-matched norm-groups with both
      techniques, pre- and postoperatively. However, duration of the surgical procedure
      and calculated blood loss were significantly lower in the ESC group (p < 0.05).
      CONCLUSION: ESC and MPP were effective techniques to normalize cephalic index
      (CI) and improve head shape at their recommended time of surgery. Measurement of
      ICV and CI with 3D photogrammetry is a valid method to objectively evaluate
      patients before and after surgery without exposing pediatric patients to ionizing
      radiation.

PMID- 29066042
TI  - Hydrogen-peroxide and silicone-hydrogel contact lenses: Worsening of external eye
      condition and tear film instability.
AB  - PURPOSE: The aim is discussing the origins of worsening of external eye condition
      (EEC) and of tear film (TF) instability after wear of silicone-hydrogel contact
      lenses (CLs) with hydrogen-peroxide (H2O2) care system. METHODS: EEC and TF
      stability were evaluated before and after 15days of wear combined with different
      care systems: (1) H2O2, (2) detergent solution and H2O2, (3) multipurpose
      solution (MPS), (4) H2O2 and artificial tears. In-vitro cell mortality tests were
      performed after 24h cell incubation with CLs treated with H2O2. Photon
      correlation spectroscopy (PCS) was carried out on tears of non-wearers and CL
      wearers who used MPS or H2O2 solution. RESULTS: Worsening of EEC was observed
      only for the group using H2O2 (group 1). In-vitro, cell mortality was found
      higher for worn CL than for unworn CLs. Worsening of TF stability was observed
      regardless of care system and also PCS results on tears of CL wearers were found
      different compared to non-wearers regardless of care system. The only observed
      remedy for tear instability of CL wearers was found to be the administration of
      artificial tears. CONCLUSIONS: Worsening of EEC of CL wearers using H2O2 is
      attributed to H2O2 scarce cleaning efficacy, which can be solved by adding a CL
      detergent solution. The origin of TF instability is found to be different. A
      remedy was found to be the administration of artificial tears, whose effect could
      be attributed either to the role of specific components or to rinsing and
      replacement of TF during wear.

PMID- 29066044
TI  - Iatrogenic solid tumors following immunosuppressive therapy.
AB  - Immunosuppression induced by chronic medication, such as occurs post
      transplantation, may increase a patient's risk of developing solid tumors. These
      are often rare tumors characterized by odd presentations. This review focuses on
      commonly encountered iatrogenic, non-hematopoietic solid tumors following
      immunotherapy and provides a practical approach to their diagnosis. All of the
      malignancies covered in this review are viral-induced. They include human
      papillomavirus (HPV)-associated carcinomas, Epstein-Barr virus (EBV)-associated
      tumors, Merkel cell polyomavirus (MCPyV)-related Merkel cell carcinoma, and Human
      Herpesvirus 8 (HHV8)-related Kaposi sarcoma. The complementary diagnostic role of
      ancillary studies, such as immunohistochemistry and in-situ hybridization that
      target these oncogenic viruses, is addressed.

PMID- 29066043
TI  - MTPSLs: New Terpene Synthases in Nonseed Plants.
AB  - Terpenes constitute a large class of plant secondary metabolites. It was once
      presumed that these compounds are biosynthesized by typical plant terpene
      synthases in all land plants. This view has changed with the identification of a
      new group of terpene synthase genes called MTPSLs for microbial terpene synthase
      like genes. MTPSLs are structurally and phylogenetically more related to
      bacterial and fungal terpene synthases than to typical plant terpene synthases.
      They are widely distributed in nonseed plants but absent in seed plants and green
      algae. Much of the terpene diversity in nonseed plants is presumed to be
      determined by MTPSLs. Phylogenetic analysis suggests that ancestral MTPSL genes
      were acquired by early land plants from bacteria and fungi through horizontal
      gene transfer.

PMID- 29066045
TI  - Medical therapy for fibroids: An overview.
AB  - Uterine fibroids are the most common benign tumours in women of reproductive age
      group and are a cause of significant healthcare burden. Although surgical
      treatments have been the traditional gold standard for symptomatic uterine
      fibroids, several medical therapeutic approaches have been used to achieve
      symptom suppression in women who wish to preserve their uterus or are at elevated
      risk of complications during surgery. Medical therapies used for uterine fibroids
      include tranexamic acid, NSAIDs, contraceptive steroids, progesterone coil, GnRH
      analogues, aromatase inhibitors, SERMs and progesterone receptor modulators. The
      levonorgestrel containing intrauterine system reduces menstrual blood loss
      associated with fibroids, but drawbacks include the possibility of device
      expulsion and fitting difficulties. The use of GnRH agonists for 3-4 months prior
      to fibroid surgery can achieve reduction in uterine volume and fibroid size. They
      are beneficial in the correction of preoperative iron deficiency anaemia, if
      present, and reduce intra-operative blood loss. Although medical treatments
      provide effective symptom relief, women resorting to these therapies should be
      made aware of the high rates of future re-intervention. It is important for
      clinicians to recognise limitations of these therapies and that appropriate
      patient selection is of utmost importance.

PMID- 29066046
TI  - Rationally designed hecogenin thiosemicarbazone analogs as novel MEK inhibitors
      for the control of breast malignancies.
AB  - Natural products have documented oncology success history as valuable scaffolds
      for selective target modulation. Herein, the sapogenin hecogenin (1) was screened
      for its anti-breast cancer inhibitory capacity using in vitro assays, including
      proliferation, cytotoxicity, migration, invasion assays, and Western blotting.
      The results identified 1 as a propitious hit with modest activities attributed to
      the concurrent down-regulation of mitogen activated protein kinase
      kinase/extracellular signal-regulated kinase (MEK) distinctive downstream
      effectors. Guided by in silico 3D-structural insights of MAPK kinase domain, an
      extension strategy was adopted at 1's C-3 and C-12 aimed at the design of novel
      hecogenin-based analogs with improved target binding affinity. Thirty-three
      analogs were prepared and tested, among which hecogenin 12-(3'-methylphenyl
      thiosemicarbazone) (30) displayed the most potent selective anticancer effects.
      Analog 30 demonstrated antiproliferative, antimigratory and anti-invasive
      activities at low MUM level, compared to the negligible effect on the non
      tumorigenic MCF-10A mammary epithelial cells. Durable regression of breast tumor
      xenografts in athymic nude mice was observed after treatments with 30, compared
      to its parent hecogenin at the same dose regimen, confirmed the hit-to-lead
      promotion of this analog. Hecogenin-12-thiosemicarbazones, represented by 30, is
      a novel MEK inhibitory lead class to control breast neoplasms.

PMID- 29066048
TI  - Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade
      Progression from Long-term Follow-up of Large Population-based Cohorts Not
      Subject to Prostate-specific Antigen Screening.
AB  - BACKGROUND: Lead time (LT) is of key importance in early detection of cancer, but
      cannot be directly measured. We have previously provided LT estimates for
      prostate cancer (PCa) using archived blood samples from cohorts followed for many
      years without screening. OBJECTIVE: To determine the association between LT and
      PCa grade at diagnosis to provide an insight into whether grade progresses or is
      stable over time. DESIGN, SETTING, AND PARTICIPANTS: The setting was three long
      term epidemiologic studies in Sweden including men not subject to prostate
      specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10
      ng/ml at blood draw and subsequently diagnosed with PCa with grade data
      available. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic
      regression was used to predict high-grade (Gleason grade group >=2 or World
      Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT,
      defined as the time between the date of elevated PSA and the date of PCa
      diagnosis with adjustment for cohort and age. RESULTS AND LIMITATIONS: The
      probability that PCa would be high grade at diagnosis increased with LT. Among
      all men combined, the risk of high-grade disease increased with LT (odds ratio
      1.13, 95% confidence interval [CI] 1.10-1.16; p<0.0001), with no evidence of
      differences in effect by age group or cohort. Higher PSA predicted shorter LT by
      0.46 yr (95% CI 0.28-0.64; p<0.0001) per 1 ng/ml increase in PSA. However, there
      was no interaction between PSA and grade, suggesting that the longer LT for high
      grade tumors is not simply related to age. Limitations include the assumption
      that men with elevated PSA and subsequently diagnosed with PCa would have had
      biopsy-detectable PCa at the time of PSA elevation. CONCLUSIONS: Our data support
      grade progression, whereby following a prostate over time would reveal
      transitions from benign to low-grade and then high-grade PCa. PATIENT SUMMARY:
      Men with a longer lead time between elevated prostate-specific antigen and
      subsequent prostate cancer diagnosis were more likely to have high-grade cancers
      at diagnosis.

PMID- 29066047
TI  - How effective are risk assessments/measures for predicting future aggressive
      behaviour in adults with intellectual disabilities (ID): A systematic review and
      meta-analysis.
AB  - BACKGROUND: Risk assessments assist professionals in the identification and
      management of risk of aggression. The present study aimed to systematically
      review evidence on the efficacy of assessments for managing the risk of physical
      aggression in adults with intellectual disabilities (ID). METHODS: A literature
      search was conducted using the databases PsycINFO, EMBASE, MEDLINE, Web of
      Science, and Google Scholar. Electronic and hand searches identified 14 studies
      that met the inclusion criteria. Standardised mean difference effect sizes Area
      Under Curve (AUC) were calculated for studies. Random effects subgroup analysis
      was used to compare different types of risk measures (Actuarial, Structured
      Professional Judgment and dynamic), and prospective vs. catch-up longitudinal
      study designs. RESULTS: Overall, evidence of predictive validity was found for
      risk measures with ID populations: (AUC)=0.724, 95% CI [0.681, 0.768]. There was
      no variation in the performance of different types of risk measures, or different
      study design. CONCLUSIONS: Risk assessment measures predict the likelihood of
      aggression in ID population and are comparable to those in mainstream
      populations. Further meta-analysis is necessary when risk measures are more
      established in this population.

PMID- 29066049
TI  - Afterglow based detection and dosimetry of beta particle irradiated ZrO2.
AB  - In this work, we report on the afterglow (AG) response characterization of
      commercially available ZrO2. Pellet shaped samples previously annealed in air at
      1000 degrees C during 24h were exposed to beta particle irradiation in the dose
      range from 0.5 up to 128Gy and their AG decay curves recorded during 600s after
      irradiation exposure. The characteristic glow curves of beta particle irradiated
      ZrO2 show two maxima located around 80 degrees C and 150 degrees C. The first one
      rapidly vanishes at room temperature, giving rise to AG. The integrated AG signal
      increases as dose increases from 0.5 to 128Gy, with a linear dependence from 0.5
      up to ca. 32Gy. Excellent reproducibility of the AG response was observed in 10
      irradiation - AG readout cycles, showing that the studied ZrO2 samples are
      reusable. The results here presented show that ZrO2 is a promising material for
      use as a radiation dosimeter based on the AG phenomenon.

PMID- 29066050
TI  - Improvement of the activity measurement method for solid dosimeters emitting X
      rays.
AB  - Today, there is growing interest for neutrons in the intermediate energy range
      between 100keV and 1MeV, which are responsible for damaging materials in reactor.
      To improve this deficiency, we use rhodium and niobium which, through the
      inelastic neutron scattering reaction, leads to the formation of 103mRh and 93mNb
      low-energy X-emitters. This paper describes the improvements and validation made
      on this type of complex measurement by X spectrometry: self-attenuation,
      fluorescence correction, and emission intensity were poorly known previously.

PMID- 29066051
TI  - Impact of Pretreatment Interstitial Lung Disease on Radiation Pneumonitis and
      Survival in Patients Treated With Lung Stereotactic Body Radiation Therapy
      (SBRT).
AB  - INTRODUCTION: The purpose of this study was to determine the impact of
      interstitial lung disease (ILD) on radiation pneumonitis (RP) and overall
      survival (OS) in lung stereotactic body radiation therapy (SBRT). METHODS:
      Patients treated with lung SBRT from 2004 to 2015 were included. Pretreatment
      computed tomography scans were reviewed and classified for interstitial changes
      by thoracic radiologists using American Thoracic Society guidelines and Washko
      and Kazerooni scores. RP was scored prospectively using Common Terminology
      Criteria for Adverse Events, version 3.0. Pretreatment imaging characteristics,
      clinical variables, and dosimetry were assessed by univariate (UVA) and
      multivariate analysis (MVA). OS was assessed by the log-rank test, and the impact
      of ILD on OS was assessed by Cox regression. RESULTS: Of the 537 patients
      assessed, 39 had interstitial changes (13 usual interstitial pneumonia [UIP], 24
      possible UIP, and 2 inconsistent with UIP). RP was significantly higher in
      patients with ILD than in patients without ILD (grade >= 2, 20.5% vs. 5.8%; P <
      .01; grade >= 3, 10.3% vs. 1.0%; P < .01). Two of 3 grade 5 RP had imaging
      features of ILD. On UVA, ILD, Washko score, lung parameters performance status,
      and dose were significant predictors of grade >= 2 RP. On MVA, ILD (odds ratio,
      5.81; 95% confidence interval, 2.28-14.83; P < .01) and mean lung dose (odds
      ratio, 1.40; 95% confidence interval, 1.14-1.71; P < .01) were predictors of RP.
      ILD did not significantly affect OS on UVA or MVA. Median survival was 27.4
      months in the ILD cohort and 34.8 in the ILD-negative cohort (P = .17).
      DISCUSSION: ILD is a significant risk factor for RP in patients treated with lung
      SBRT. Computed tomography scans should be reviewed for evidence of ILD prior to
      SBRT.

PMID- 29066052
TI  - Strategy for an abbreviated in-house qualification of a commercially available
      Rapid Microbiology Method (RMM) for canadian regulatory approval.
AB  - BACKGROUND AIMS: Cell therapy products (CTP) typically require full sterility,
      endotoxin and Mycoplasma testing before product release. Often this is not
      feasible with fresh cells, and sponsors may rely on rapid microbiological methods
      (RMM). RMM must be qualified in-house using the sponsor's facilities, equipment,
      consumables, cells and matrices to meet regulatory approval. Herein, we present a
      cost-effective strategy to conduct an in-house abbreviated qualification of a
      commercially available RMM kit to meet Health Canada regulatory requirements.
      METHODS: We performed an abbreviated qualification using a polymerase chain
      reaction (PCR)-based Mycoplasma testing method involving assay sensitivity and
      ruggedness, based on an experimental plan that was pre-approved by Health Canada.
      Briefly, investigational CTPs were tested in-house using a PCR-based Mycoplasma
      detection kit. Assay sensitivity was determined using a 10-fold dilution series
      of genomic DNA of only two Mycoplasma species, Mycoplasma arginini and Mycoplasma
      hominis in the absence of CTP-matrix as the kit had been previously validated
      against nine species. Matrix interference was measured by testing independent CTP
      samples. Testing by different operators on different days measured ruggedness.
      RESULTS: The RMM Mycoplasma qualification exceeded sensitivity (4 genome copies
      per reaction for M. arginini and 0.12 genome copies per reaction for M. hominis)
      and met ruggedness requirements without matrix interference, as required by the
      Pharmacopoeial guidelines (Ph. Eur. 2.6.7 and USP <1223>). DISCUSSION: Our
      approach represents a minimal qualification that can be performed by an academic
      institution while ensuring regulatory compliance for implementing RMM testing for
      in-process and product-release testing of CTPs.

PMID- 29066053
TI  - Insomnia heterogeneity: Characteristics to consider for data-driven multivariate
      subtyping.
AB  - Meta-analyses and systematic reviews have reported surprisingly few consistent
      insomnia-characteristics with respect to cognitions, mood, traits, history of
      life events and family history. One interpretation of this limited consistency is
      that different subtypes of insomnia exist, each with its own specific
      multivariate profile of characteristics. Because previously unrecognized subtypes
      will be differentially represented in individual studies and dilute effect sizes
      of subtype-dependent characteristics of importance, they are unlikely to be
      reported consistently in individual studies, let alone in meta-analyses. This
      review therefore aims to complement meta-analyses by listing previously reported
      psychometric characteristics of insomnia, irrespective of the degree of
      consistency over studies. The review clearly indicates that characteristics of
      insomnia may not be limited to sleep. Reports suggest that at least some
      individuals with insomnia may deviate from people without sleep complaints with
      respect to demographics, mental and physical health, childhood trauma, life
      events, fatigue, sleepiness, hyperarousal, hyperactivity, other sleep disorders,
      lifetime sleep history, chronotype, depression, anxiety, mood, quality of life,
      personality, happiness, worry, rumination, self-consciousness, sensitivity,
      dysfunctional beliefs, self-conscious emotion regulation, coping, nocturnal
      mentation, wake resting-state mentation, physical activity, food intake,
      temperature perception and hedonic evaluation. The value of this list of
      characteristics is that 1) internet has now made it feasible to asses them all in
      a large sample of people suffering from insomnia, and 2) statistical methods like
      latent class analysis and community detection can utilize them for a truly bottom
      up data-driven search for subtypes. The supplement to this review provides a
      blueprint of this multivariate approach as implemented in the Sleep registry
      platform (www.sleepregistry.nl), that allows for bottom-up subtyping and fosters
      cross-cultural comparison and worldwide collaboration on insomnia subtype finding
      - and beyond.

PMID- 29066054
TI  - The validity of the heat tolerance test in prediction of recurrent exertional
      heat illness events.
AB  - OBJECTIVES: Heat-tolerance-testing (HTT) protocol is used as a screening test for
      secondary prevention of exertional heat illness (EHI) in the military. Subjects
      whose test results are positive (heat-intolerant, HI) are presumed to be at
      higher risk of repeated EHI events than heat-tolerant subjects (HT) and are
      therefore prevented from return to combat duty, but may return to unsupervised
      recreational activity. Our aim was to determine, whether HTT results predict the
      risk of repeated episodes of exertional heat illness (EHI). DESIGN: Retrospective
      cohort. METHODS: One-hundred-forty-five subjects (110 HT, 35 HI) who were
      diagnosed with an EHI event by a physician and underwent HTT during 2008-2015
      were contacted and asked about recurrence of EHI. Incidence of recurrent events
      was reported as number of cases per 1000 person-years. Ratio of events among HI
      and HT individuals was presented as rate ratio (RR) and its 95% confidence
      interval. RESULTS: Of the 145 patients, six (4.1%) had experienced recurrent EHI
      events (10.63 per 1000PY): four HI subjects (11.4%, 26.6 per 1000PY) and two HT
      (1.8%, 4.8 per 1000PY) (RR=5.504, CI 95%=1.01-30, p=0.027). Only one of the six
      recurrent events was a heat stroke (HT individual), other five were heat
      exhaustions. Sensitivity, specificity and diagnostic accuracy of HTT were 66.7%,
      77.7% and 77.2%, respectively. CONCLUSIONS: The risk of EHI recurrence is
      measurable and can be discussed with patients before they return to sports. A
      referral to HTT can be considered, as negative HTT result is associated with
      substantial and significant EHI risk reduction.

PMID- 29066055
TI  - Response to letter to the Editor Re: Skeletal muscle functional and structural
      adaptations after eccentric overload flywheel resistance training: A systematic
      review and meta-analysis.

PMID- 29066056
TI  - [A 31 year-old patient with polydipsia].

PMID- 29066057
TI  - The impact of pathological complete response after neoadjuvant chemoradiotherapy
      in locally advanced squamous cell carcinoma of esophagus.
AB  - BACKGROUND: The impact of pathological complete response after neoadjuvant
      chemoradiotherapy on survival of patients with squamous cell carcinoma of
      esophagus is still controversial. We retrospectively investigated the survival
      outcome in this group of patients. METHODS: Ninety-eight patients with locally
      advanced squamous cell carcinoma of esophagus, who received neoadjuvant
      chemoradiotherapy were included in this retrospective analysis. Treatment
      protocols were radiotherapy with standard dose 50.4 Gy/28 fr, and chemotherapy
      with cisplatin 20 mg/m2 and 5-FU 800 mg/m2 for 4 days given on week 1 and 5.
      After neoadjuvant chemoradiotherapy is completed, patients who were eligible for
      surgery received surgery within 4-6 weeks. Patients who were not suitable for
      surgery were shifted to definite chemoradiotherapy. The primary end points were
      overall survival and progression-free survival. RESULTS: Sixty-eight patients out
      of the ninety-eight patients received surgery after neoadjuvant
      chemoradiotherapy. There were 32 patients who achieved pathological complete
      response with a pCR rate of 47%. Thirty patients were shifted to definite
      concurrent chemoradiotherapy. The 2-year overall survival rate was 81.3% in the
      patients whose tumors showed a pCR and 58.3% in the patients with tumors that had
      a pathological partial response (p = 0.025). The 2-year overall survival in
      patients who received neoadjuvant chemoradiotherapy followed by surgery and
      definite chemoradiotherapy were 69.1% and 40.0%, respectively. There are 13
      patients experienced grade 3-4 adverse event. CONCLUSION: Pathological complete
      response after neoadjuvant chemoradiotherapy is associated with a significant
      survival benefit in patients with locally advanced squamous cell carcinoma of
      esophagus. The toxicities related to neoadjuvant chemoradiotherapy were
      tolerable.

PMID- 29066058
TI  - Inhibitory and Coactivating Receptors Recognising the Same Ligand: Immune
      Homeostasis Exploited by Pathogens and Tumours.
AB  - Coactivating and inhibitory receptors that share at least one ligand interact
      with a wide variety of ligands, indicating their importance in a range of
      situations. Here, we discuss principles of mainly human paired receptor function
      and ligand recognition, and possible therapeutic implications of targeting these
      receptors in cancer, autoimmune diseases, and allergy. We summarise and emphasise
      the idea that these receptors, which have evolved in part in response to pathogen
      pressure, fine-tune the immune response, preserve homeostasis, and that pathogens
      and tumours use the dominance of the inhibitory receptors over the coactivating
      receptors to avoid immune elimination. Finally, we discuss the options of using
      paired receptors and their ligand for immune cell education and therapy.

PMID- 29066060
TI  - Re-introducing the delto-acromial perforator flap: Clinical experience and
      cadaver dissection.
AB  - BACKGROUND: Although perforator flaps from the pectoral branch of the thoraco
      acromial (TA) axis have been well-described, there are few reports of perforator
      flaps based on the delto-acromial (DA) branches. We have found a reliable
      perforator coming off the DA branch of the TA axis, and have named a flap based
      on this vessel the delto-acromial perforator (DAP) flap. We describe our
      experience with the DAP flap together with a fresh cadaver anatomical study.
      METHODS: A retrospective review of all DAP flaps performed between December 2012
      and January 2015 at our institution, with analysis of operative details, flap
      characteristics and surgical outcomes. We performed fresh cadaver dissection on 5
      hemi-chest walls. RESULTS: The main cutaneous perforator from the deltoid and/or
      acromial branches is found at the delto-pectoral groove, 8 cm lateral to the TA
      axis and 8 cm inferior to the acromio-clavicular joint. Five patients underwent
      DAP flap reconstruction. Three were pedicled and 2 were free flaps. Average
      pedicle length from the origin of the DA branch was 8 cm, with an arterial
      diameter of at least 1 mm and vein diameter 1.5 mm. All flaps survived
      completely. Cadaver dissection showed a consistent perforator arising from the
      common delto-acromial branch in 4 cadavers, and from the deltoid branch in 1
      cadaver. CONCLUSIONS: The DAP flap is a good addition to the armamentarium of
      reconstructive surgeons when a relatively thin fasciocutaneous flap with minimal
      hair is desired. It may be used for free tissue or locoregional transfer.

PMID- 29066059
TI  - Evaluation of the effect of an innovative automated text messaging service on
      patient experience in day-case hand trauma surgery.

PMID- 29066061
TI  - Reduction mammoplasty in adolescents and elderly: A ten year case series
      analyzing age related outcome with focus on safety and complications.
AB  - INTRODUCTION: Reduction mammoplasty alleviates symptoms of macromastia in various
      ways. Current study results mainly identify perioperative risk factors for middle
      aged patients. We investigated a large series of consecutive breast reductions
      procedures to study whether patients' age at the time of operation is related to
      the postoperative outcome. METHODS: We retrospectively reviewed all non-oncologic
      breast reduction procedures at a single institution over a ten year time period,
      analyzing patients (age, BMI, comorbidities, medication) and operation specific
      characteristics' (pedicle, nipple-to-sternal notch, resection weight,
      complications) to identify risk factors related to patients' age at the time of
      operation. Patients were therefore divided into three groups, according to their
      age (group I <= 20 years, group II >=60 years, group III 21 to 59 years).
      RESULTS: 539 patients were included in the study, in total 1065 reduction
      mammoplasties were performed over a ten year period. The overall complication
      rate was 33% (n = 175). Excluding minor complications, the total complication
      rate was 9.5% (n = 51). High body mass index (>=30 kg/m2) (p = 0.02) could be
      identified as a statistically significant risk factor for major and minor
      complications. Smoking (p = 0.09) and age >= 60 years (p = 0.08) showed a
      tendency toward higher risk for major and minor complications. CONCLUSION: This
      study shows an increased risk for complications when performing reduction
      mammoplasty in older patients, presumably due to the higher prevalence of
      comorbidities in this patient group as compared to young patients.

PMID- 29066062
TI  - Comments on: "The medium-term effects of diadynamic currents in chronic low back
      pain; TENS versus diadynamic currents: A randomized, follow-up study".

PMID- 29066064
TI  - Comment on: early weight loss after laparoscopic sleeve gastrectomy predicts
      midterm weight loss in morbidly obese Asians.

PMID- 29066063
TI  - Formation of the Protein Corona: The Interface between Nanoparticles and the
      Immune System.
AB  - The interaction of inorganic nanoparticles and many biological fluids often
      withstands the formation of a Protein Corona enveloping the nanoparticle. This
      Protein Corona provides the biological identity to the nanoparticle that the
      immune system will detect. The formation of this Protein Corona depends not only
      on the composition of the nanoparticle, its size, shape, surface state and
      exposure time, but also on the type of media, nanoparticle to protein ratio and
      the presence of ions and other molecular species that interfere in the
      interaction between proteins and nanoparticles. This has important implications
      on immune safety, biocompatibility and the use of nanoparticles in medicine.

PMID- 29066065
TI  - Disadvantaged? Dual level learning in pre-registration graduate entry nursing and
      midwifery education: An evaluation.
AB  - Preparation for health or social work professional registration is offered at
      undergraduate and postgraduate level and the requirement to co-teach is often
      resource and logistically mediated. This learning context creates opportunity to
      explore student perceptions of learning in dual level cohorts. Evaluative
      research of dual level learning is limited but suggests that the quality of
      learning experiences is influenced by factors such as establishing a cohort
      identity, managing individual perceptions of ability and the value of individual
      contributions to the cohort experience. Completing health care students from one
      HEI who were part of a co-taught cohort were asked to evaluate their learning
      experiences, using an anonymous questionnaire. A total of 81 undergraduate and 18
      postgraduate students participated. All responses submitted were from Nursing and
      Midwifery programmes. Responses suggested lack of consistency in student
      expectations. Whilst the majority of undergraduates were satisfied with their
      experience, post graduate students were less so. Good practice in facilitation of
      learning was identified but was inconsistent and some undergraduates felt
      overawed by their post graduate peers. The findings of this small study suggest
      it is possible to achieve positive learning experiences for co taught cohorts but
      this requires careful and consistent planning and management.

PMID- 29066066
TI  - A historical perspective with current opinion on the management of atrophic
      mandibular fractures.
AB  - The management of atrophic mandibular fractures has been a challenge for
      maxillofacial surgeons for decades. During the past 70 years, various techniques
      for treating edentulous mandibular fractures have been advocated. These
      techniques have been praised, criticized, abandoned, improved, and used in
      combination with other methods. Although some of the principles of management
      outlined before the end of World War II are still valid in today's technological
      era, other concepts did not survive the test of time. The aim of this paper is to
      examine the evolution of treatment modalities for the management of atrophic
      mandibular fractures that have been employed over the years. Debates and
      discussions generated by this topic are included. Current techniques and
      treatment philosophies with thoughts for future therapies are provided.

PMID- 29066067
TI  - Salivary duct cyst of accessory parotid gland in contact with the
      temporomandibular joint.
AB  - A 60-year-old woman presented with a painless swelling in the right preauricular
      region. Physical examination revealed a soft, nontender, oval-shaped lump in this
      location. Computed tomography indicated an anterolateral cystic lesion that was
      attached to the condyle of the mandible and to the accessory parotid gland.
      Differential diagnoses included ganglion cyst, synovial cyst of the
      temporomandibular joint, and accessory parotid gland cyst. Surgical removal of
      the cyst was performed with the patient under general anesthesia. The specimen
      was 18 * 20 * 18 mm in size; it contained fluid that was clear, slightly yellow,
      and amylase positive. Hematoxylin and eosin staining revealed that a bilayer
      cuboidal epithelium lined the cyst wall. Immunohistochemical analyses of the cyst
      wall showed strong expression of cytokeratin and weak expression of vimentin. The
      final diagnosis was a salivary duct cyst. The postoperative course was uneventful
      except for a transient facial motor paresis.

PMID- 29066068
TI  - Music Soothes the Savage Beast.

PMID- 29066069
TI  - Radiation Exposure and Patient Dose in Cardiology.

PMID- 29066071
TI  - Altered regional and circuit resting-state activity in patients with occult
      spastic diplegic cerebral palsy.
AB  - BACKGROUND: Very few studies have been made to investigate functional activity
      changes in occult spastic diplegic cerebral palsy (SDCP). The purpose of this
      study was to analyze whole-brain resting state regional brain activity and
      functional connectivity (FC) changes in patients with SDCP. METHODS: We examined
      12 occult SDCP and 14 healthy control subjects using resting-state functional
      magnetic resonance imaging. The data were analyzed using Resting-State fMRI Data
      Analysis Toolkit (REST) software. The regional homogeneity (ReHo), amplitude of
      low-frequency fluctuations (ALFF), and whole brain FC of the motor cortex and
      thalamus were analyzed and compared between the occult SDCP and control groups.
      RESULTS: Compared with the control group, the occult SDCP group showed decreased
      ReHo regions, including the bilateral frontal, parietal, and temporal lobes, the
      cerebellum, right cingulate gyrus, and right lenticular nucleus, whereas an
      increased ReHo value was observed in the left precuneus, calcarine, fusiform
      gyrus, and right precuneus. Compared with the control group, no significant
      differences in ALFF were noted in the occult SDCP group. With the motor cortex as
      the region of interest, the occult SDCP group showed decreased connectivity
      regions in the bilateral fusiform and lingual gyrus, but increased connectivity
      regions in the contralateral precentral and postcentral gyrus, supplementary
      motor area, and the ipsilateral postcentral gyrus. With the thalamus being
      regarded as the region of interest, the occult SDCP group showed decreased
      connectivity regions in the bilateral basal ganglia, cingulate, and prefrontal
      cortex, but increased connectivity regions in the bilateral precentral gyrus, the
      contralateral cerebellum, and inferior temporal gyrus. CONCLUSIONS: Resting-state
      regional brain activities and FC changes in the patients with occult SDCP
      exhibited a special distribution pattern, which is consistent with the pathology
      of the disease.

PMID- 29066070
TI  - Net Revenue Analysis of Inpatient and Emergency Department Thyroid Ultrasound at
      a US Quaternary Care Center From 2012 to 2015.
AB  - PURPOSE: The aim of this study was to understand the financial ramifications of
      performing nonemergent inpatient and emergency department (ED) adult thyroid
      ultrasound studies at a US quaternary care center. METHODS: A HIPAA-compliant,
      institutional review board-exempt retrospective review of 10,334 thyroid
      ultrasound studies performed between February 2012 and December 2015 was
      conducted. Demographic, imaging, clinical, and financial data were reviewed.
      Labor cost analysis was calculated using national salary data and local
      scheduling practices. Professional and technical reimbursement and utilization
      trends were compared across 149 payers, multiple time spans, and visit settings
      (outpatient, ED, and inpatient). RESULTS: Most thyroid ultrasound studies were
      performed on outpatients (97.4% [10,069 of 10,334]), with a minority performed on
      inpatients (2.1% [217 of 10,334]) or in the ED (0.5% [48 of 10,334]). Man-hour
      cost of performing thyroid ultrasound was higher in the inpatient and ED settings
      ($15.30) compared with the outpatient setting ($7.65). Professional reimbursement
      was highest in the outpatient setting (mean, $37.39) and varied by payer
      (proprietary data; SD, $21.36 per examination). Technical reimbursement loss due
      to diagnosis-related group billing for inpatients and admitted-via-ED patients
      was $44,376; this was partly compensated ($9,309) by technical reimbursement from
      discharged-from-ED patients (mean technical reimbursement loss, $746 per month).
      Utilization increased year by year and correlated with Medicare volumes.
      Inpatient utilization was highest in Medicare patients; outpatient and ED
      utilization was highest for patients with private payers. CONCLUSIONS: Net
      revenue loss from and imaging volumes of inpatient and ED nonemergent adult
      thyroid ultrasound studies are low.

PMID- 29066072
TI  - Intrauterine inflammation, infection, or both (Triple I): A new concept for
      chorioamnionitis.
AB  - Chorioamnionitis is a common cause of preterm birth and may cause adverse
      neonatal outcomes, including neurodevelopmental sequelae. Chorioamnionitis has
      been marked to a heterogeneous setting of conditions characterized by infection
      or inflammation or both, followed by a great variety in clinical practice for
      mothers and their newborns. Recently, a descriptive term: "intrauterine
      inflammation or infection or both" abbreviated as "Triple I" has been proposed by
      a National Institute of Child Health and Human Development expert panel to
      replace the term chorioamnionitis. It is particularly important to recognize that
      an isolated maternal fever does not automatically equate to chorioamnionitis.
      This article will review the current literature on chorioamnionitis, and
      introduce the concept of Triple I, as well as recommendations for assessment and
      management of pregnant women and their newborns with a diagnosis of Triple I.

PMID- 29066073
TI  - Factors Influencing Overall Survival for Patients With Metastatic Clear-Cell
      Renal-Cell Carcinoma in Daily Practice.
AB  - PURPOSE: To describe factors associated with overall survival (OS) among patients
      with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution
      of systemic therapies. PATIENTS AND METHODS: Two hundred twenty-four consecutive
      patients with histologically confirmed mccRCC who received targeted therapy on
      first-line treatment between January 2007 and March 2015 were included. The
      primary end point was OS for metastatic first-line or second-line treatment. An
      analysis of prognostic factors of long survival was performed using a 2-step
      approach: univariate, then multivariate analysis. RESULTS: Median OS [95%
      confidence interval] was 19.4 months [16.1-24.9]. Three prognostic factors were
      identified in first-line treatment: Memorial Sloan Kettering Cancer Center
      (MSKCC) favorable and intermediate risks (hazard ratio [95% confidence interval]
      = 0.362 [0.207-0.630] and 0.561 [0.393-0.801], respectively, P = 4.10-4),
      metastasectomy (0.667 [0.468-0.951], P = .03), and lack of lymph node metastasis
      (0.715 [0.513-0.994], P = .049). In second-line treatment, median OS [95%
      confidence interval] was 11.0 months [8.9-14.4] for 167 patients. Three different
      prognostic factors predicted long survival: toxicity for first-line treatment
      discontinuation (HR [95% confidence interval] = 0.298 [0.180-0.493], P < 10-4),
      duration of disease control in first-line therapy (0.961 [0.942-0.979], P = 2.10
      4), and MSKCC favorable and intermediate risks (0.461 [0.252-0.843] and 0.936
      [0.607-1.443], respectively, P = .02). CONCLUSION: These real-life data confirm
      the positive impact of targeted therapy in the mccRCC setting. Moreover, it
      emphasizes the importance of considering many factors in order to better estimate
      prognosis in patient pretreated with systemic therapy.

PMID- 29066074
TI  - Metastatic Adenocarcinoma of the Epididymis: A Case Report and Brief Literature
      Review.

PMID- 29066075
TI  - Dynamics and equilibria of living systems: Comment on "Answering Schrodinger's
      question: A free-energy formulation" by Maxwell James Desormeau Ramstead et al.

PMID- 29066076
TI  - Seeing mental states: An experimental strategy for measuring the observability of
      other minds.
AB  - Is it possible to perceive others' mental states? Are mental states visible in
      others' behavior? In contrast to the traditional view that mental states are
      hidden and not directly accessible to perception, in recent years a
      phenomenologically-motivated account of social cognition has emerged: direct
      social perception. However, despite numerous published articles that both defend
      and critique direct perception, researchers have made little progress in
      articulating the conditions under which direct perception of others' mental
      states is possible. This paper proposes an empirically anchored approach to the
      observability of others' mentality - not just in the weak sense of discussing
      relevant empirical evidence for and against the phenomenon of interest, but also,
      and more specifically, in the stronger sense of identifying an experimental
      strategy for measuring the observability of mental states and articulating the
      conditions under which mental states are observable. We conclude this article by
      reframing the problem of direct perception in terms of establishing a definable
      and measurable relationship between movement features and perceived mental
      states.

PMID- 29066079
TI  - Diagnosis of Aortic Dissection Presenting as ST-Elevation Myocardial Infarction
      using Point-Of-Care Ultrasound.
AB  - BACKGROUND: Aortic dissections can present with a broad spectrum of signs and
      symptoms, making them difficult to diagnose in the emergency department (ED).
      Aortic dissections can cause occlusion of the coronary arteries, mimicking an
      acute ST-elevation myocardial infarction (STEMI). Emergency point-of-care
      ultrasound (POCUS) may be a useful diagnostic tool to help differentiate aortic
      dissection from a primary myocardial infarction. CASE REPORT: A 69-year-old man
      with no medical history presented to our ED complaining of chest pain. His
      electrocardiogram revealed new and dynamic ST-segment elevations consistent with
      a septal myocardial infarction. While the patient was being prepared for the
      cardiac catheterization laboratory, the treating emergency physician performed a
      POCUS study. The scan revealed an echogenic flap in the ascending aorta,
      significant aortic regurgitation, and intimal flaps in the carotid artery and
      abdominal aorta. The diagnosis of a type A aortic dissection was confirmed with
      computed tomography angiography. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: Differentiating an acute STEMI from an aortic dissection can be extremely
      difficult in the ED. It is important not to delay reperfusion therapy for
      patients with a true STEMI; however, the same treatment can be lethal for
      patients with aortic dissection. Emergency POCUS is a fast and accessible test
      that has been shown to have high specificity for the diagnosis of aortic
      dissection in the ED. POCUS may be a useful tool to help emergency physicians
      diagnose aortic dissection presenting with STEMI.

PMID- 29066078
TI  - Computational neuroscience across the lifespan: Promises and pitfalls.
AB  - In recent years, the application of computational modeling in studies on age
      related changes in decision making and learning has gained in popularity. One
      advantage of computational models is that they provide access to latent variables
      that cannot be directly observed from behavior. In combination with experimental
      manipulations, these latent variables can help to test hypotheses about age
      related changes in behavioral and neurobiological measures at a level of
      specificity that is not achievable with descriptive analysis approaches alone.
      This level of specificity can in turn be beneficial to establish the identity of
      the corresponding behavioral and neurobiological mechanisms. In this paper, we
      will illustrate applications of computational methods using examples of lifespan
      research on risk taking, strategy selection and reinforcement learning. We will
      elaborate on problems that can occur when computational neuroscience methods are
      applied to data of different age groups. Finally, we will discuss potential
      targets for future applications and outline general shortcomings of computational
      neuroscience methods for research on human lifespan development.

PMID- 29066077
TI  - Applying novel technologies and methods to inform the ontology of self
      regulation.
AB  - Self-regulation is a broad construct representing the general ability to recruit
      cognitive, motivational and emotional resources to achieve long-term goals. This
      construct has been implicated in a host of health-risk behaviors, and is a
      promising target for fostering beneficial behavior change. Despite its clear
      importance, the behavioral, psychological and neural components of self
      regulation remain poorly understood, which contributes to theoretical
      inconsistencies and hinders maximally effective intervention development. We
      outline a research program that seeks to define a neuropsychological ontology of
      self-regulation, articulating the cognitive components that compose self
      regulation, their relationships, and their associated measurements. The ontology
      will be informed by two large-scale approaches to assessing individual
      differences: first purely behaviorally using data collected via Amazon's
      Mechanical Turk, then coupled with neuroimaging data collected from a separate
      population. To validate the ontology and demonstrate its utility, we will then
      use it to contextualize health risk behaviors in two exemplar behavioral groups:
      overweight/obese adults who binge eat and smokers. After identifying ontological
      targets that precipitate maladaptive behavior, we will craft interventions that
      engage these targets. If successful, this work will provide a structured,
      holistic account of self-regulation in the form of an explicit ontology, which
      will better clarify the pattern of deficits related to maladaptive health
      behavior, and provide direction for more effective behavior change interventions.

PMID- 29066081
TI  - ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for
      Multimodality Imaging in Valvular Heart Disease: A Report of the American College
      of Cardiology Appropriate Use Criteria Task Force, American Association for
      Thoracic Surgery, American Heart Association, American Society of
      Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society,
      Society for Cardiovascular Angiography and Interventions, Society of
      Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic
      Resonance, and Society of Thoracic Surgeons.
AB  - This document is 1 of 2 companion appropriate use criteria (AUC) documents
      developed by the American College of Cardiology, American Association for
      Thoracic Surgery, American Heart Association, American Society of
      Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society,
      Society for Cardiovascular Angiography and Interventions, Society of
      Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic
      Resonance, and Society of Thoracic Surgeons. This document addresses the
      evaluation and use of multimodality imaging in the diagnosis and management of
      valvular heart disease, whereas the second, companion document addresses this
      topic with regard to structural heart disease. Although there is clinical
      overlap, the documents addressing valvular and structural heart disease are
      published separately, albeit with a common structure. The goal of the companion
      AUC documents is to provide a comprehensive resource for multimodality imaging in
      the context of valvular and structural heart disease, encompassing multiple
      imaging modalities. Using standardized methodology, the clinical scenarios
      (indications) were developed by a diverse writing group to represent patient
      presentations encountered in everyday practice and included common applications
      and anticipated uses. Where appropriate, the scenarios were developed on the
      basis of the most current American College of Cardiology/American Heart
      Association guidelines. A separate, independent rating panel scored the 92
      clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9
      indicate that a modality is considered appropriate for the clinical scenario
      presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate
      for the clinical scenario, and scores of 1 to 3 indicate that a modality is
      considered rarely appropriate for the clinical scenario. The primary objective of
      the AUC is to provide a framework for the assessment of these scenarios by
      practices that will improve and standardize physician decision making. AUC
      publications reflect an ongoing effort by the American College of Cardiology to
      critically and systematically create, review, and categorize clinical situations
      where diagnostic tests and procedures are utilized by physicians caring for
      patients with cardiovascular diseases. The process is based on the current
      understanding of the technical capabilities of the imaging modalities examined.

PMID- 29066080
TI  - Piper nigrum extract ameliorated allergic inflammation through inhibiting
      Th2/Th17 responses and mast cells activation.
AB  - Piper nigrum (Piperaceae) is commonly used as a spice and traditional medicine in
      many countries. P. nigrum has been reported to have anti-oxidant, anti-bacterial,
      anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties.
      However, the effect of P. nigrum on allergic asthma has not been known. This
      study investigated the effect of P. nigrum ethanol extracts (PNE) on airway
      inflammation in asthmatic mice model. In the ovalbumin (OVA)-induced allergic
      asthma model, we analysed the number of inflammatory cells and cytokines
      production in bronchoalveolar lavage fluid (BALF) and lung tissue; histological
      structure; as well as the total immunoglobulin (Ig)E, anti-OVA IgE, anti-OVA IgG1
      and histamine levels in serum. The oral administration (200 mg/kg) of PNE reduced
      the accumulation of inflammatory cells (eosinophils, neutrophils in BALF and mast
      cells in lung tissue); regulated the balance of the cytokines production of Th1,
      Th2, Th17 and Treg cells, specifically, inhibited the expressions of GATA3, IL-4,
      IL-6, IL-1beta, RORgammat, IL-17A, TNF-alpha and increased the secretions of IL
      10, INF-gamma in BALF and lung homogenate. Moreover, PNE suppressed the levels of
      total IgE, anti-OVA IgE, anti-OVA IgG1 and histamine release in serum. The
      histological analysis showed that the fibrosis and infiltration of inflammatory
      cells were also ameliorated in PNE treated mice. On the other hand, PNE inhibited
      the allergic responses via inactivation of rat peritoneal mast cells
      degranulation. These results suggest that PNE has therapeutic potential for
      treating allergic asthma through inhibiting Th2/Th17 responses and mast cells
      activation.

PMID- 29066082
TI  - Performance of a Simplified Dichotomous Phenotypic Classification of Bicuspid
      Aortic Valve to Predict Type of Valvulopathy and Combined Aortopathy.
AB  - BACKGROUND: A simplified classification of bicuspid aortic valve (BAV) morphology
      using only the orientation of fused cusps was recently proposed. The aim of this
      study was to test whether it is useful for showing an association with the type
      of valvulopathy or aortopathy. METHODS: BAV phenotype was retrospectively
      classified in 681 patients (mean age, 59 +/- 12 years; 424 men) who underwent
      aortic valve surgery. Each BAV was classified using both dichotomous (right and
      left coronary cusp fusion [CCF] vs mixed cusp fusion [MCF]) and conventional
      methods, and its association with the dominant valvulopathy (aortic stenosis [AS]
      vs regurgitation) and concomitant aortic surgery was analyzed. Four cardiologists
      individually reviewed transthoracic echocardiographic images of 100 randomly
      selected patients to compare the feasibility and accuracy of the two
      classification methods. RESULTS: The frequencies of BAV CCF and MCF were 53% (n =
      361) and 47% (n = 320), respectively. AS was the predominant cause of surgery (n
      = 546 [80%]), and concomitant aortic surgery was done in 31% (n = 214). Patients
      with BAV MCF showed a higher frequency of AS (89% vs 73%, P < .001) and aortic
      surgery (38% vs 26%, P < .001) than those with BAV CCF. There were independent
      associations between BAV MCF and AS (odds ratio, 3.32; 95% CI, 1.99-5.54; P <
      .001) as well as aortic surgery (odds ratio, 1.76; 95% CI, 1.26-2.45; P = .001).
      The feasibility of the classification methods did not differ, but dichotomous
      classification revealed higher accuracy than conventional (87% [95% CI, 84.1%
      90.7%] vs 70% [95% CI, 65.0%-74.3%]) for all four examiners, with higher kappa
      coefficients representing interrater agreement (kappa = 0.73 +/- 0.06 to 0.83 +/-
      0.06 [dichotomous method] vs 0.51 +/- 0.06 to 0.73 +/- 0.06 [conventional
      method]). CONCLUSIONS: The dichotomous classification method is useful for
      showing the association with the type of valvulopathy or aortopathy, with better
      diagnostic performance than the conventional method.

PMID- 29066083
TI  - Sleep-Related Painful Erections-A Case Series of 24 Patients Regarding
      Diagnostics and Treatment Options.
AB  - BACKGROUND: Patients with sleep-related painful erections (SRPEs) have deep
      penile pain during nocturnal erection that wakes them up and disturbs their
      nights of sleep. This rare parasomnia is poorly recognized by general
      practitioners and by urologists and sexologists. AIM: To gain more insight into
      diagnostics and therapeutic options. METHODS: Data from a series of 24
      consecutive patients who presented with SRPEs at the outpatient clinic from 1996
      to 2015 were retrospectively analyzed. Additional questionnaires were completed
      to complement data and to obtain information about follow-up. Long-term treatment
      efficacy of baclofen was assessed using the Wilcoxon signed rank test. OUTCOMES:
      SRPEs were not associated with urologic, surgical, or psychiatric history or with
      serum testosterone levels. The mean doctors' delay was 3.5 years. 14 of the 24
      patients were treated with baclofen (10-75 mg). In 11 of them, complete remission
      was observed within a few weeks. 2 of the 3 remaining patients noticed a slight
      improvement of SPRE symptoms and only 1 patient experienced no effect at all.
      After an average follow-up of 4.5 years, only 41.6% of patients who had used
      baclofen were satisfied with their SRPEs. The others (58.4%) were dissatisfied,
      mostly owing to relapse of symptoms after the discontinuation of baclofen. Other
      treatment forms were applied sporadically, with strongly varying results.
      CLINICAL IMPLICATIONS: This overview of SRPE contributes to a better clinical
      understanding and recognition of the phenomenon and provides new, more
      constructed advice about therapeutic implications, especially concerning the use
      of baclofen. STRENGTHS AND LIMITATIONS: This study provides a systematic overview
      of a relatively large series of patients with SRPE, which provides substantiated
      treatment advice. However, treatment efficacy was based mainly on the patients'
      subjective perception and it was not possible to compare the results of baclofen
      with other forms of pharmacologic treatment, because these alternative drugs were
      applied only sporadically. Nevertheless, this study is directional for future
      research. CONCLUSIONS: This study confirmed a long doctors' delay in patients
      with SRPE. There was no association between SRPEs and comorbidity and total serum
      testosterone levels. Treatment with baclofen proved successful and safe in the
      short term. Long-term feasibility needs further investigation. Vreugdenhil S,
      Weidenaar AC, de Jong IJ, van Driel MF. Sleep-Related Painful Erections-A Case
      Series of 24 Patients Regarding Diagnostics and Treatment Options. Sex Med
      2017;5:e237-e243.

PMID- 29066085
TI  - Delineating the relationship between Point A prescription dose and pelvic lymph
      node doses in intracavitary high-dose-rate brachytherapy treatment of cervical
      cancer for use in low- and middle-income countries.
AB  - PURPOSE: To define the relationship between the Point A prescription dose and the
      dose delivered to various pelvic lymph node groups during high-dose-rate (HDR)
      brachytherapy treatment of cervical cancer. In less developed countries,
      brachytherapy is often done without three-dimensional image guidance, instead
      relying on plain radiography and prescription to Point A. A defined relationship
      between Point A dose and lymph node doses would help physicians in these health
      care settings to more accurately estimate nodal doses. METHODS AND MATERIALS:
      Treatment data from 50 fractions of HDR brachytherapy of cervical cancer were
      reviewed, the pelvic lymph nodes were contoured, and dose-volume histogram
      parameters were obtained. Dose-volume histogram parameters for each contour were
      normalized as a percentage of the corresponding Point A dose. All nodal groups
      were divided into left and right sides, except the presacral nodal group. RESULTS
      AND CONCLUSIONS: Mean Point A doses were bilateral (Bil) 5.92 Gy +/- 0.58, left
      (L) 5.93 +/- 0.59, and right (R) 5.92 +/- 0.59. Mean normalized D90 values for
      the various lymph node groups were as follows-obturator: Bil 20.3% +/- 4.5, L
      20.5% +/- 4.4, and R 20.2% +/- 5.2; external iliac: Bil 9.5% +/- 2.9, L 10.0% +/-
      3.1, and R 9.5% +/- 3.0; internal iliac: Bil 12.2% +/- 3.5, L 12.1% +/- 3.4, and
      R 12.9% +/- 4.7; common iliac: Bil 4.3% +/- 1.6, L 4.3% +/- 1.6, and R 4.3% +/-
      1.7; and presacral: 8.7% +/- 3.4. These relationships can serve as a useful tool
      for evaluating lymph node doses during HDR brachytherapy of cervical cancer in
      facilities performing two-dimensional treatment planning and those with limited
      resources.

PMID- 29066084
TI  - Comparative Genomic Profiling of Matched Primary and Metastatic Tumors in Renal
      Cell Carcinoma.
AB  - BACKGROUND: Next-generation sequencing (NGS) studies of matched pairs of primary
      and metastatic tumors in renal cell carcinoma (RCC) have been limited to small
      cohorts. OBJECTIVE: To evaluate the discordance in somatic mutations between
      matched primary and metastatic RCC tumors. DESIGN, SETTING, AND PARTICIPANTS:
      Primary tumor (P), metastasis (M), and germline DNA from 60 patients with RCC was
      subjected to NGS with a targeted exon capture-based assay of 341 cancer
      associated genes. Somatic mutations were called using a validated pipeline.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Mutations were classified as
      shared (S) or private (Pr) in relation to each other within individual P-M pairs.
      The concordance score was calculated as (S-Pr)/(S+Pr). To calculate enrichment of
      Pr/S mutations for a particular gene, we calculated a two-sided p value from a
      binomial model for each gene with at least ten somatic mutation events, and also
      implemented a separate permutation test procedure. We adjusted p values for
      multiple hypothesis testing using the Benjamini-Hochberg procedure. The mutation
      discordance was calculated using Mann-Whitney U tests according to gene mutations
      or metastatic sites. RESULTS AND LIMITATIONS: Twenty-one pairs (35%) showed Pr
      mutations in both P and M samples. Of the remaining 39 pairs (65%), 14 (23%) had
      Pr mutations specific to P samples, 12 (20%) had Pr mutations to M samples, and
      13 (22%) had identical somatic mutations. No individual gene mutation was
      preferentially enriched in either P or M samples. P-M pairs with SETD2 mutations
      demonstrated higher discordance than pairs with wild-type SETD2. We observed that
      patients who received therapy before sampling of the P or M tissue had higher
      concordance of mutations for P-M pairs than patients who did not (Mann-Whitney
      p=0.088). CONCLUSIONS: Our data show mutation discordance within matched P-M RCC
      tumor pairs. As most contemporary precision medicine trials do not differentiate
      mutations detected in P and M tumors, the prognostic and predictive value of
      mutations in P versus M tumors warrants further investigation. PATIENT SUMMARY:
      In this study we evaluated the concordance of mutations between matched primary
      and metastatic tumors for 60 kidney cancer patients using a panel of 341 cancer
      genes. Forty-seven patients carried nonidentical cancer gene mutations within
      their matched primary-metastatic pair. The mutation profile of the primary tumor
      alone could compromise precision in selecting effective targeted therapies and
      result in suboptimal clinical outcomes.

PMID- 29066087
TI  - Another building in the IPF Manhattan plot skyline.

PMID- 29066086
TI  - [HBV infection: Screening and treatment for oncology patients].
AB  - Patients with chronic hepatitis B infection are at risk of viral reactivation
      when treated by immuno- or chemotherapy, with potentially serious or even fatal
      consequences. This article proposes an overview on screening strategies and
      antiviral treatment recommendations for oncology patients. We have learned in
      hematology that reactivations are commun with rituximab and prophylactic
      treatment is recommanded for any patient who has been in contact with the virus.
      The risk appears to be lower with cytotoxics but has been far less studied. The
      recommandations are not formally consensual and upcoming studies will help to
      establish clearer practice guidelines.

PMID- 29066088
TI  - UK air pollution declines but more needs to be done.

PMID- 29066089
TI  - Implications for the science of air pollution and health.

PMID- 29066091
TI  - Influenza vaccination in tropical and subtropical areas.

PMID- 29066092
TI  - Longitudinal monitoring of liver stiffness by acoustic radiation force impulse
      imaging in patients with chronic hepatitis B receiving entecavir.
AB  - BACKGROUND: Acoustic radiation force impulse (ARFI) imaging measures liver
      stiffness (LS), which significantly correlates with the stage of liver fibrosis
      in treatment-naive patients with chronic hepatitis B (CHB). AIM: We aimed to
      prospectively assess the clinical usefulness of ARFI during long-term antiviral
      therapy in CHB. METHOD: Seventy-one CHB patients were consecutively recruited and
      paired liver biopsies were performed in 27 patients. LS was assessed by ARFI
      semiannually during entecavir therapy. RESULTS: LS gradually decreased with
      treatment and continued to decrease after normalization of alanine
      aminotransaminase. Overall, 97.2% patients achieved improvement of LS, whereas
      19.7% patients had more than 30% reduction in LS values between baseline and week
      104. Multivariate linear regression analysis showed that the degree of LS
      reduction significantly correlated with the baseline levels of LS value, platelet
      and cholinesterase. In the 27 patients who underwent paired liver biopsies, LS
      significantly correlated with stage of fibrosis and inflammatory grade at
      baseline. LS values decreased more significantly in patients with fibrosis
      regression than those with static histological fibrosis. CONCLUSION: In CHB
      patients, LS assessed by ARFI was gradually reduced during antiviral therapy.
      Longitudinal monitoring of LS may be a promising noninvasive assessment of
      fibrosis regression during long-term antiviral therapy in CHB. Further large
      sample studies are needed.

PMID- 29066093
TI  - Anthropometric dimensions provide reliable estimates of abdominal adiposity: A
      validation study.
AB  - Abdominal fat accumulation is a major risk factor for cardiometabolic morbidity
      and mortality. The purpose of the study is to assess the possibility of
      developing accurate estimation equations based on body measurements to determine
      total abdominal (TFA), subcutaneous (SFA) and visceral fat area (VFA). Hungarian
      volunteers (n=198) aged between 20 and 81 years were enrolled in the study, which
      was conducted between July and November 2014. All persons underwent
      anthropometric measurements and computer tomographic (CT) scanning. Sex-specific
      multiple linear regression analyses were conducted in a subgroup of 98
      participants to generate estimation models, then Bland-Altman's analyses were
      applied in the cross-validation group to compare their predictive efficiency. The
      variables best predicting VFA were hip circumference, calf circumference and
      waist-to-hip ratio (WHR) for males (R2=0.713; SEE=5602.1mm2) and sagittal
      abdominal diameter (SAD), WHR, thigh circumference and triceps skinfold for
      females (R2=0.845; SEE=3835.6mm2). The SFA prediction equation included SAD,
      thigh circumference and abdominal skinfold for males (R2=0.848; SEE=4124.1mm2),
      body mass index and thigh circumference for females (R2=0.861; SEE=5049.7mm2).
      Prediction accuracy was the highest in the case of TFA: hip circumference and WHR
      for males (R2=0.910; SEE=5637.2mm2), SAD, thigh circumference and abdominal
      skinfold for females (R2=0.915; SEE=6197.5mm2) were used in the equations. The
      results suggested that deviations in the predictions were independent of the
      amount of adipose tissue. Estimation of abdominal fat depots based on
      anthropometric traits could provide a cheap, reliable method in epidemiologic
      research and public health screening to evaluate the risk of cardiometabolic
      events.

PMID- 29066090
TI  - Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis
      in people of European ancestry: a genome-wide association study.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung
      disease with high mortality, uncertain cause, and few treatment options. Studies
      have identified a significant genetic risk associated with the development of
      IPF; however, mechanisms by which genetic risk factors promote IPF remain
      unclear. We aimed to identify genetic variants associated with IPF susceptibility
      and provide mechanistic insight using gene and protein expression analyses.
      METHODS: We used a two-stage approach: a genome-wide association study in
      patients with IPF of European ancestry recruited from nine different centres in
      the UK and controls selected from UK Biobank (stage 1) matched for age, sex, and
      smoking status; and a follow-up of associated genetic variants in independent
      datasets of patients with IPF and controls from two independent US samples from
      the Chicago consortium and the Colorado consortium (stage 2). We investigated the
      effect of novel signals on gene expression in large transcriptomic and genomic
      data resources, and examined expression using lung tissue samples from patients
      with IPF and controls. FINDINGS: 602 patients with IPF and 3366 controls were
      selected for stage 1. For stage 2, 2158 patients with IPF and 5195 controls were
      selected. We identified a novel genome-wide significant signal of association
      with IPF susceptibility near A-kinase anchoring protein 13 (AKAP13; rs62025270,
      odds ratio [OR] 1.27 [95% CI 1.18-1.37], p=1.32 * 10-9) and confirmed previously
      reported signals, including in mucin 5B (MUC5B; rs35705950, OR 2.89 [2.56-3.26],
      p=1.12 * 10-66) and desmoplakin (DSP; rs2076295, OR 1.44 [1.35-1.54], p=7.81 * 10
      28). For rs62025270, the allele A associated with increased susceptibility to IPF
      was also associated with increased expression of AKAP13 mRNA in lung tissue from
      patients who had lung resection procedures (n=1111). We showed that AKAP13 is
      expressed in the alveolar epithelium and lymphoid follicles from patients with
      IPF, and AKAP13 mRNA expression was 1.42-times higher in lung tissue from
      patients with IPF (n=46) than that in lung tissue from controls (n=51).
      INTERPRETATION: AKAP13 is a Rho guanine nucleotide exchange factor regulating
      activation of RhoA, which is known to be involved in profibrotic signalling
      pathways. The identification of AKAP13 as a susceptibility gene for IPF increases
      the prospect of successfully targeting RhoA pathway inhibitors in patients with
      IPF. FUNDING: UK Medical Research Council, National Heart, Lung, and Blood
      Institute of the US National Institutes of Health, Agencia Canaria de
      Investigacion, Innovacion y Sociedad de la Informacion, Spain, UK National
      Institute for Health Research, and the British Lung Foundation.

PMID- 29066095
TI  - Rapidly declining HIV infection in MSM in central London.

PMID- 29066097
TI  - Correction to Lancet Diabetes Endocrinol 2018; 6: 130-42.

PMID- 29066094
TI  - ABCG5/G8 gene is associated with hypercholesterolemias without mutation in
      candidate genes and noncholesterol sterols.
AB  - CONTEXT: Approximately 20% to 40% of clinically defined familial
      hypercholesterolemia (FH) cases do not show a causative mutation in candidate
      genes (mutation-negative FH), and some of them may have a polygenic origin.
      OBJECTIVE: The aim of this work was to study the prevalence of ABCG5/G8 genetic
      variants in mutation-negative FH, as defects in these genes relate to intestinal
      hyperabsorption of cholesterol and thus ABCG5/G8 variants could explain in part
      the mechanism of hypercholesterolemia. DESIGN, SETTING, AND PATIENTS: We
      sequenced the ABCG5/G8 genes in 214 mutation-negative FH and 97 controls.
      Surrogate markers of cholesterol absorption (5alpha-cholestanol, beta-sitosterol,
      campesterol, stigmasterol, and sitostanol) were quantified by high-performance
      liquid chromatography-tandem mass spectrometry in both studied groups. RESULTS:
      We found 8 mutation-negative FH patients (3.73%) with a pathogenic mutation in
      ABCG5/G8 genes. We observed significantly higher concentration of surrogate
      markers of cholesterol absorption in mutation-negative FH than in controls. In
      addition, we found significantly higher concentrations of cholesterol absorption
      markers in mutation-negative FH with ABCG5/G8 defects than in mutation-negative,
      ABCG5/G8-negative FH. A gene score reflecting the number of common single
      nucleotide variants associated with hypercholesterolemia was significantly higher
      in cases than in controls (P = .032). Subjects with a gene score above the mean
      had significantly higher 5alpha-cholestanol and stigmasterol than those with a
      lower gene score. CONCLUSIONS: Mutation-negative FH subjects accumulate an excess
      of rare and common gene variations in ABCG5/G8 genes. This variation is
      associated with increased intestinal absorption of cholesterol, as determined by
      surrogate makers, suggesting that these loci contribute to hypercholesterolemia
      by enhancing intestinal cholesterol absorption.

PMID- 29066096
TI  - Interventions to prevent global childhood overweight and obesity: a systematic
      review.
AB  - In view of the prevalence, health consequences, and costs of childhood obesity,
      there has been substantial interest in identifying effective interventions to
      prevent excess weight gain in young people. In this systematic review, we expand
      on previous reviews of obesity prevention interventions by including recent
      studies (until May 23, 2017) from all parts of the world. We searched MEDLINE,
      Embase, CINAHL Plus, Web of Science, CAB Abstracts, and PAIS Index and included
      randomised controlled trials, quasi-experimental studies, or natural experiments
      with: (1) a control group; (2) minimum follow-up of 12 months for community-based
      and home-based interventions or 6 months for school-based and preschool-based
      interventions; and (3) a primary outcome of BMI, BMI Z score, BMI percentile,
      body fat percentage, skinfold thickness, waist circumference, or prevalence of
      overweight or obesity. School-based interventions with combined diet and physical
      activity components and a home element (n=41) had greatest effectiveness;
      evidence in support of the effect of preschool-based (n=6), community-based
      (n=7), and home-based (n=2) interventions was limited by a paucity of studies and
      heterogeneity in study design. The effectiveness of school-based interventions
      that combined diet and physical activity components suggests that they hold
      promise for childhood obesity prevention worldwide. More research with rigorous
      evaluation and consistent reporting is needed in non-school settings and in
      combinations of settings.

PMID- 29066098
TI  - Brown-Sequard syndrome and cervical post-traumatic subarachnoid hematoma.
AB  - Cervical Traumatic SSH are very rare in literature. They are usually caused by
      cardiopulmonary diseases that increase vascular pressure causing spinal vessels
      rupture. In thoracolumbar spine, the spinal puncture is the most common cause.
      The ventrolateral position is even more unusual. In traumatic brain injury (TBI),
      an abrupt extension-flexion movement could have caused the rupture of
      subarachnoid vessels. This, accompanied by the slowed blood "wash out" (probably
      due to the previous osteoarthrosis and spinal canal stenosis), led to the
      formation of an organized clot, which caused an acute spinal cord compression
      syndrome. Cervical subarachnoid spinal hematoma can present as Brown-Sequard
      syndrome. The treatment is prompt surgical removal and decompression. The
      posterior approach (partial hemilaminectomy with or without laminoplasty) with
      microsurgical technique is feasible, fast and simple to evacuate the hematoma
      with good results. Surgical nuances in posterior approach are: small spinal
      canal, difficulty in mobilizing the cervical cord, these haematomas are wrapped
      and attached to the spinal cord or nerve roots by multiple arachnoid bands,
      requiring techniques of Microdissection for its evacuation unlike the epidural
      and subdural haematomas that are easily aspirated. Here, we report a unique case
      of a ventrolateral SSH due to TBI.

PMID- 29066099
TI  - Effects of home prothrombin international ratio (PT-INR) management in children
      with mechanical prosthetic valves - Importance of individual correlations between
      laboratory and CoaguChek device PT-INRs.
AB  - BACKGROUND: Warfarin administration is essential but requires difficult
      management and frequent clinic visits in patients with mechanical prosthetic
      atrioventricular valve replacement (MPAVVR). This study investigated how home
      prothrombin international ratio (PT-INR) monitoring with CoaguChek(r) (Roche
      Diagnostics, Basel, Switzerland) safely reduced clinic visits in children with
      MPAVVR. We also compared individual correlations between the CoaguChek and
      laboratory PT-INR. METHODS: This study included four pediatric patients who
      started frequent warfarin home-monitoring after MPAVVR (three mitral valves and
      one tricuspid valve). We collected information regarding the number of outpatient
      clinic visits and measurements of PT-INR before and after starting home CoaguChek
      monitoring (each one year) from medical records. We also compared individual
      correlations between laboratory and CoaguChek PT-INR in three patients. RESULTS:
      No major clinical events were encountered during the study period. The ratio of
      outpatient clinic visits in the second year to those in the first year was
      decreased in all patients (0.30-0.66). The ratio of the numbers of home
      measurements to all PT-INR measurements in the second year ranged from 0.55 to
      0.64 indicating that CoaguChek home monitoring approximately halved the number of
      outpatient clinic visits. CoaguChek measurements tended to be slightly
      overestimated in two patients but were greatly underestimated in one patient.
      CONCLUSIONS: CoaguChek home monitoring in children with MPAVVR reduced the number
      of their clinic visits without compromising the safety of warfarin management.
      Given considerable individual differences in correlations between CoaguChek and
      laboratory PT-INR, individual correlation needs to be identified to fairly
      interpret the CoaguChek PT-INR values.

PMID- 29066100
TI  - The Selvester QRS score as a predictor of cardiac events in nonischemic dilated
      cardiomyopathy.
AB  - BACKGROUND: Myocardial fibrosis is associated with poor prognosis in nonischemic
      dilated cardiomyopathy (NIDCM) patients. The Selvester QRS score on 12-lead
      electrocardiogram is associated with both the amount of myocardial scar and poor
      prognosis in myocardial infarction patients. However, its use in NIDCM patients
      is limited. We investigated the prognostic value of the QRS score and its
      association with collagen volume fraction (CVF) in NIDCM patients. METHODS: We
      enrolled 91 consecutive NIDCM patients (66 men, 53+/-13 years) without permanent
      pacemakers or cardiac resynchronization therapy devices. The Selvester QRS score
      was calculated by two expert cardiologists at NIDCM diagnosis. All patients were
      followed up over 4.5+/-3.2 years. Cardiac events were defined as a composite of
      cardiac death, hospitalization for worsening heart failure, and lethal
      arrhythmia. We also evaluated CVF using endomyocardial biopsy samples. RESULTS:
      At baseline, the left ventricular ejection fraction was 32+/-9%, plasma brain
      natriuretic peptide level was 80 [43-237] pg/mL, and mean Selvester QRS score was
      4.1 points. Twenty cardiac events were observed (cardiac death, n=1;
      hospitalization for worsening heart failure, n=16; lethal arrhythmia, n=3). Cox
      proportional hazard regression analysis revealed that the Selvester QRS score was
      an independent determinant of cardiac events (hazard ratio, 1.32; 95% confidence
      interval, 1.05-1.67; p=0.02). The best cut-off value was determined as 3 points,
      with 85% sensitivity and 47% specificity (area under the curve, 0.688, p=0.011).
      In Kaplan-Meier survival analysis, the QRS score >=3 group had more cardiac
      events than the QRS score <3 group (log-rank, p=0.007). Further, there was a
      significant positive correlation of Selvester QRS score with CVF (r=0.46,
      p<0.001). CONCLUSIONS: The Selvester QRS score can predict future cardiac events
      in NIDCM, reflecting myocardial fibrosis assessed by CVF.

PMID- 29066101
TI  - Quality of meal protein determines anabolic response in older adults.
AB  - BACKGROUND & AIMS: It has been demonstrated that the relative content and profile
      of essential amino acids (EAA) play a determining role for stimulation of muscle
      protein synthesis (MPS) following intake of pure EAA or protein alone. METHODS:
      To test if this also holds in the context of mixed meals at both whole body and
      muscle levels, twelve older subjects (57-74 yrs) received primed continuous
      infusion of L-[ring-2H5]phenylalanine and L-[ring-2H2]tyrosine over a 9-h
      experimental period to determine whole body protein kinetics and MPS in the
      fasted state and following consumption of egg-based (EGG) or cereal-based
      (CEREAL) isocaloric and isonitrogenous breakfast. A standardized lunch, primarily
      consisting of beef protein was also consumed by each group. Whole body protein
      kinetics [protein synthesis (PS), breakdown (PB), and net balance (NB)] were
      expressed as changes from basal fasted period. RESULTS: We found that EGG
      breakfast resulted in a greater NB through a greater suppression of PB compared
      with the CEREAL breakfast. The greater NB during the post-breakfast period with
      the EGG was normalized following the standard lunch despite the sustained
      elevations in plasma EAA concentrations. However, the EGG breakfast stimulated
      both PS and PB compared with the CEREAL breakfast during the post-lunch period.
      MPS was not different between meals despite larges differences in the plasma EAA
      responses. CONCLUSIONS: We conclude that in the context of mixed meals, quality
      of protein affects NB through changes in protein breakdown and affects protein
      turnover following subsequent meal intake.

PMID- 29066102
TI  - In situ surface protein conjugation of small molecules for SPR immunoassays.
AB  - Solution based protein conjugation of small molecules involves multiple steps of
      chemical syntheses, bio-conjugation and purifications which are labor intensive
      and time-consuming. Since many small molecules have limited water solubility,
      conjugation to a protein is also a relatively low efficiency process in aqueous
      solutions. In this study, a model in situ protein conjugation of small molecules
      was achieved onto SPR surfaces, using progesterone and ovalbumin as a model small
      molecule-protein system. The in situ protein conjugation not only eliminated the
      requirement for wet chemistry, but also provided an easy way to optimize the
      assay performance and screen various molecular linkers.

PMID- 29066103
TI  - Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin.
AB  - OBJECTIVE: Gentamicin (GM) is an effective antibiotic against severe infection
      but has limitations related to nephrotoxicity. In this study, we investigated
      whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the
      nephrotoxic effect of GM in rats. METHODS: Rats were divided into five groups.
      Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group
      4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats
      were euthanized by cervical decapitation and then blood samples and kidneys were
      collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant
      and antioxidant parameters, as well as histopathological examination of kidney
      tissues were assessed. RESULTS: Gentamicin administration caused a severe
      nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM
      1 level as compared with the controls. Moreover, a significant increase in serum
      malondialdehyde, reduced glutathione. Histopathological examination of renal
      tissue in gentamisin administered group, there were extremly pronounced necrotic
      tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli.
      BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine,
      urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment
      was significantly decreased necrotic tubuli and hyalen deposition in gentamisin
      plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically
      significant alterations in these nephrotoxicity parameters when compared with GM
      group but histopathological examination of renal tissue in GM+CoQ10 administered
      group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation
      in tubuli. CONCLUSION: The results from our study indicate that BFT supplement
      attenuates gentamicin-induced renal injury via the amelioration of oxidative
      stress and inflammation of renal tubular cells.

PMID- 29066104
TI  - Complexities of patients and management approaches challenge tests of
      effectiveness.

PMID- 29066105
TI  - In Vivo Kinematic Comparison of a Bicruciate Stabilized Total Knee Arthroplasty
      and the Normal Knee Using Fluoroscopy.
AB  - BACKGROUND: The bicruciate stabilized (BCS) total knee arthroplasty (TKA)
      features asymmetrical bearing geometry and dual substitution for the anterior
      cruciate ligament and posterior cruciate ligament (PCL). Previous TKA designs
      have not fully replicated normal knee motion, and they are characterized by lower
      magnitudes of overall rollback and axial rotation than the normal knee. METHODS:
      In vivo kinematics were derived for 10 normal knees and 40-second generation BCS
      TKAs all implanted by a single surgeon. Mobile fluoroscopy and three-dimensional
      to-two-dimensional registration was used to analyze anterior-posterior motion of
      the femoral condyles and femorotibial axial rotation during weight-bearing
      flexion. Statistical analysis was conducted at the 95% confidence level. RESULTS:
      From 0 degrees  to 30 degrees  of knee flexion, the BCS subjects exhibited
      similar patterns of femoral rollback and axial rotation compared to normal knee
      subjects. From 30 degrees  to 60 degrees  of knee flexion, BCS subjects
      experienced negligible anterior-posterior motions and axial rotation while normal
      knees continued to rollback and externally rotate. Between 60 degrees  and 90
      degrees  the BCS resumed posterior motion and, after 90 degrees , axial rotation
      increased in a normal-like fashion. CONCLUSION: Similarities in early flexion
      kinematics suggest that the anterior cam-post is supporting normal-like anterior
      posterior motion in the BCS subjects. Likewise, lateral femoral rollback and
      external rotation of the femur in later flexion provides evidence for appropriate
      substitution of the PCL via the posterior cam-post. Being discrete in nature, the
      dual cam-post mechanism does not lend itself to adequate substitution of the
      cruciate ligaments in mid-flexion during which anterior cruciate ligament tension
      is decreasing and PCL tension is increasing in the normal knee.

PMID- 29066106
TI  - Quantitative Effect of Pelvic Position on Radiographic Assessment of Acetabular
      Component Position.
AB  - BACKGROUND: Intraoperative fluoroscopy aims to improve component position in
      total hip arthroplasty. Measurement bias related to image quality, however, has
      not been quantified. We aim to quantify measurement bias in the interpretation of
      acetabular component position as a function of pelvis and fluoroscopic beam
      position in a simulated supine total hip arthroplasty model. METHODS: Posterior
      anterior pelvis and hip images were obtained using a previously described pelvic
      model with known acetabular component position. Pelvic position was varied in 5
      degrees  increments of pelvis rotation (iliac-obturator) and tilt (inlet-outlet),
      and in 1 cm increments from beam center in cranial-caudal and medial-lateral
      planes. Multiple regression analyses were conducted to evaluate the relationship
      between the resulting bias in interpretation of component position relative to
      pelvis position. RESULTS: Anteversion and abduction measurement bias increased
      exponentially with increasing deviation in rotation and tilt. Greater bias
      occurred for anteversion than for abduction. Hip centered images were less
      affected by pelvis malposition than pelvis centered images. Deviations of beam
      center within 5 cm in the coronal plane did not introduce measurement bias
      greater than 5 degrees . An arbitrarily defined acceptable bias of +/-5 degrees 
      for both abduction and anteversion was used to identify a range of optimum pelvic
      positioning each for hip and pelvis centered imaging. CONCLUSION: Accurate
      measurement of acetabular component abduction and anteversion, especially
      anteversion, is sensitive to proper pelvic position relative to the chosen
      radiographic plane. An acceptable measurement bias of +/-5 degrees  is achieved
      when the pelvis is oriented within a newly identified range of optimum pelvic
      positioning.

PMID- 29066107
TI  - Clinical and Radiographic Outcomes at 25-30 Years of a Hip Stem Fully Coated With
      Hydroxylapatite.
AB  - BACKGROUND: Little is known about the survival of total hip arthroplasty implants
      with bioactive coatings beyond the first 20 years. The authors aimed to report
      survival of a tapered hip stem fully coated with hydroxylapatite (HA) at follow
      up of 25-30 years. METHODS: Of the original series of 320 patients (347 hips), 12
      patients (12 hips) had stem and cup revisions, 54 patients (55 hips) had cup
      revisions, 17 patients (17 hips) had liner exchange. A total of 207 patients (225
      hips) died with stems in place and 21 patients (24 hips) could not be reached.
      This left a cohort of 80 patients (86 hips) with their original stem for
      assessment. Survival was analyzed using the Kaplan-Meier (KM) method and
      cumulative incidence function (CIF). RESULTS: Considering stem revision as
      endpoint, the revision risk calculated using the KM method was 6.3%, whereas
      using the CIF it was 3.7%. Considering any reoperation as endpoint, the revision
      risk calculated using the KM method was 41.2%, whereas using the CIF it was
      25.9%. The Harris Hip Score for 77 patients (18 hips) was 81.6 +/- 15.2. Standard
      x-rays were available for 52 hips (49 patients), and 10 (19.2%) showed
      radiolucencies <2 mm thick. CONCLUSION: This study is the first to report
      outcomes of an HA-coated stem beyond 25 years. The survival of stem compares
      favorably with long-term survival of the Charnley cemented stem, and with shorter
      term registry studies. The stem achieved its intended purpose of total
      osteointegration in the long-term, although the proximolateral region remains
      susceptible to radiolucencies.

PMID- 29066109
TI  - Wear Analysis of Highly Cross-Linked Polyethylene in Young and Active Patients at
      Average Fourteen Years: A Concise Follow-Up of a Previous Report.
AB  - BACKGROUND: Concerns persist regarding the oxidative stability of annealed highly
      cross-linked polyethylene (HXLPE) and hence its wear performance especially long
      term in young and active patients. The purpose of this study is to assess the
      wear rates and clinical outcomes of a first-generation annealed HXLPE. METHODS:
      Forty-six patients (57 hips) with noncemented fixation, a mean age of 53 years,
      and a mean University of California Los Angeles activity score of 8 underwent
      primary total hip arthroplasty. A 28-mm femoral head against HXLPE liner was used
      in all cases. Linear wear rates were measured by 2 independent observers.
      Radiological and clinical assessments were recorded. RESULTS: At a mean of 14
      years (range 10-17), the wear rate was 0.03 mm/y (SD +/-0.02). There were no
      revisions for wear-related complications. Using revision for wear-related
      complications as an endpoint, the survivorship was 100% and we observed no
      osteolysis. Western Ontario and McMaster Universities Osteoarthritis Index,
      patient administered questionnaire, and Hospital for Special Surgery hip scores
      were 91/100, 5/100, and 37/40 respectively. CONCLUSION: This study confirms that
      a first-generation annealed HXLPE shows excellent wear and clinical results at 10
      17 years in young and active patients. Oxidative degradation of an annealed HXLPE
      does not adversely affect wear and shows no other wear-related complications.

PMID- 29066110
TI  - Hospital Consumer Assessment of Healthcare Providers and Systems Scores Do Not
      Predict Outcomes After Total Hip Arthroplasty.
AB  - BACKGROUND: With the establishment of the Hospital Value-Based Purchasing
      program, the Hospital Consumer Assessment of Healthcare Providers and Systems
      (HCAHPS) score has been incorporated into the calculation of the total
      performance score, which determines redistribution of up to 2% of Medicare
      payments. This study aims to assess whether the HCAHPS score correlates with
      validated outcome measures after total hip arthroplasty. METHODS: Data from 63
      patients who underwent a total hip arthroplasty and completed both an HCAHPS
      score and patient-reported outcome measures (PROMs) at our institution during the
      study period from January 1, 2015 to September 2016 were analyzed. The HCAHPS
      overall hospital rating scores were correlated with the preoperative to
      postoperative change in validated PROMs, namely EuroQol-EQ-5D Instrument and Hip
      Disability and Osteoarthritis Outcome Score. RESULTS: There was no statistically
      significant correlation between the HCAHPS overall hospital rating score and
      PROMs. CONCLUSION: This study shows a lack of correlation between established
      validated PROMs used in orthopedic surgery, and the HCAHPS survey scores, an
      important determinant of compensation in the pay-for-performance reimbursement
      models.

PMID- 29066108
TI  - The Impact of Hospital Volume on Racial Differences in Complications,
      Readmissions, and Emergency Department Visits Following Total Joint Arthroplasty.
AB  - BACKGROUND: Minority patients are at higher risk for complications and
      readmissions after total hip and knee arthroplasty. They are also more likely to
      undergo joint replacement in lower volume centers, which is associated with
      poorer outcomes. It is unknown whether these disparities simply reflect
      disproportionate use of lower volume centers. This study evaluates the impact of
      hospital volume on racial differences in outcomes following joint replacement.
      METHODS: Patients who underwent total hip or knee arthroplasty between 2006 and
      2013 in New York and Florida were identified through the Healthcare Cost and
      Utilization Project State Inpatient Databases. Complications, readmissions, and
      emergency department (ED) visits within 90 days were compared by hospital volume.
      Relative risks were calculated with generalized estimating equations for risk
      factors associated with adverse outcomes. RESULTS: Race/ethnicity was not
      associated with readmission following hip replacement. Black race was associated
      with readmission following knee replacement (relative risk [RR] 1.16). Black race
      was associated with ED visits following hip replacement (RR 1.29) and knee
      replacement (RR 1.33). Hispanic ethnicity was associated with ED visits following
      knee replacement (RR 1.15), but not hip replacement. These associations did not
      change after adjusting for hospital volume. CONCLUSION: Adjusting for hospital
      volume does not alter the risk of readmissions and ED use associated with
      minority race/ethnicity, suggesting that hospital volume alone may be
      insufficient to explain racial differences in outcome.

PMID- 29066111
TI  - Internet Promotion of Direct Anterior Approach Total Hip Arthroplasty by Members
      of the American Association of Hip and Knee Surgeons.
AB  - BACKGROUND: The direct anterior approach (DAA) in total hip arthroplasty is of
      significant interest to both patients and surgeons, largely due to intense
      marketing. This study addressed the question, "What is the level of promotion of
      DAA total hip arthroplasty on the internet by American Association of Hip and
      Knee Surgeons (AAHKS) members?" METHODS: An internet search was performed to
      identify surgeon-specific websites for each member of the AAHKS using the
      members' full name and a previously published set of criteria. Each website was
      evaluated utilizing a questionnaire to systematically identify claims made
      regarding proposed DAA-specific risks, benefits, as well as the presence/absence
      of supporting data. RESULTS: We identified 1855 qualified websites. The DAA was
      referenced on 22.8% (423/1855) of these websites. Claims regarding DAA-specific
      benefits included less invasive/muscle sparing (46.3%), quicker recovery (45.2%),
      decreased pain (28.1%), decreased hospital stay (22.0%), and decreased
      dislocation risk (16.3%). Potential DAA risks including lateral femoral cutaneous
      nerve injury, periprosthetic/greater trochanteric fracture, and wound
      complication/hematoma were addressed on only 4.7%, 3.1%, and 1.7% of websites,
      respectively. Supporting peer-reviewed literature was identified on only 3.6% of
      DAA websites. CONCLUSION: Over one-fifth of AAHKS members promoted the DAA on the
      internet. Member websites claimed DAA benefits such as faster recovery and
      decreased pain approximately 9 times more frequently than any potential risk of
      the procedure (P < .001). While AAHKS policy does not regulate member marketing,
      it is the responsibility of all orthopedic surgeons to disseminate accurate,
      validated information concerning the procedures we perform.

PMID- 29066112
TI  - Costs and Risk Factors for Hospital Readmission After Periprosthetic Knee
      Fractures in the United States.
AB  - BACKGROUND: Periprosthetic fractures (PPFX) around total knee arthroplasty (TKA)
      are devastating complications with significant morbidity. With growing healthcare
      costs, hospital readmissions have become a marker for quality healthcare
      delivery. However, little is known about the risk factors or costs associated
      with readmission after treatment of PPFX. We sought to identify the patient
      demographics, prevalence of treatment types (open reduction internal fixation
      [ORIF] vs revision TKA), 30 and 90-day readmission rates, costs of initial
      treatment and readmission, and risk factors for readmission. METHODS: We used the
      2013 Nationwide Readmissions Database to select patients who underwent TKA,
      revision TKA, and treatment of PPFX with either ORIF or revision TKA. The 90-day
      readmission rate was determined through a survival analysis, and risk factors
      were identified using a cox proportional hazards model that adjusted for patient
      and hospital characteristics. RESULTS: We identified 1526 patients with PPFX
      treated with ORIF and 1458 treated with revision TKA. Ninety-day readmissions
      were 20.5% and 21.8%, respectively. Patients with ORIF were more often female and
      had multiple medical comorbidities. Patient factors associated with readmission
      included advanced age, male gender, comorbidities, discharge to a skilled nursing
      facility or home with health aide, and Medicare or Medicaid insurance. Treatment
      at a teaching hospital was the only hospital-associated risk factor identified.
      ORIF cost USD 25,539 and revision THA cost USD 37,680, with associated
      readmissions costing 15,269 and 16,806, respectively. CONCLUSION: PPFX results in
      greater costs compared to primary and revision TKA. This study highlights risk
      factors for readmission after PPFX treatment.

PMID- 29066113
TI  - Estimating the effect of the reorganization of interactions on the adaptability
      of species to changing environments.
AB  - A major challenge in community ecology is to understand how species respond to
      environmental changes. Previous studies have shown that the reorganization of
      interactions among co-occurring species can modulate their chances to adapt to
      novel environmental conditions. Moreover, empirical evidence has shown that these
      ecological dynamics typically facilitate the persistence of groups of species
      rather than entire communities. However, so far, we have no systematic
      methodology to identify those groups of species with the highest or lowest
      chances to adapt to new environments through a reorganization of their
      interactions. Yet, this could prove extremely valuable for developing new
      conservation strategies. Here, we introduce a theoretical framework to estimate
      the effect of the reorganization of interactions on the adaptability of a group
      of species, within a community, to novel environmental conditions. We introduce
      the concept of the adaptation space of a group of species based on a feasibility
      analysis of a population dynamics model. We define the adaptation space of a
      group as the set of environmental conditions that can be made compatible with its
      persistence thorough the reorganization of interactions among species within the
      group. The larger the adaptation space of a group, the larger its likelihood to
      adapt to a novel environment. We show that the interactions in the community
      outside a group can act as structural constraints and be used to quantitatively
      compare the size of the adaptation space among different groups of species within
      a community. To test our theoretical framework, we perform a data analysis on
      several pairs of natural and artificially perturbed ecological communities.
      Overall, we find that the groups of species present in both control and perturbed
      communities are among the ones with the largest adaptation space. We believe that
      the results derived from our framework point out towards new directions to
      understand and estimate the adaptability of species to changing environments.

PMID- 29066114
TI  - Tissue transport affects how treatment scheduling increases the efficacy of
      chemotherapeutic drugs.
AB  - A method to predict the effect of tissue transport on the scheduling of
      chemotherapeutic treatment could increase efficacy. Many drugs with desirable
      pharmacokinetic properties fail in vivo due to poor transport through tissue. To
      predict the effect of treatment schedule on drug efficacy we developed an in
      silico method that integrates diffusion through tissue and cell binding into a
      pharmacokinetic model. The model was evaluated with an array of theoretical drugs
      that had different rates of diffusivity, binding, and clearance. The efficacy of
      each drug, quantified as the fraction of cells killed, was calculated for twenty
      dosage schedules. Simulations showed that efficacy strongly depended on tissue
      transport, with a range of 0.00 to 99.99%, despite each drug having equal plasma
      areas under the curve (AUC). For most drugs, schedules that increased exposure
      also increased efficacy. Drugs with fast clearance benefited the most from
      increasing the number of doses and this was most effective for those with
      intermediary binding. All drugs with slow diffusivity were ineffective. For a
      subset of drugs, increasing the number of doses decreased efficacy. This
      phenomenon was unexpected because, when considering uptake into tissue, sustained
      plasma levels from multiple doses are generally assumed to be more effective.
      This counterintuitive decrease in efficacy was caused by drug retention within
      tumor tissue. These results established a set of rules that suggests how
      transport parameters affect the efficacy of drugs at different schedules. The two
      most predominant rules are (1) multiple doses improve efficacy for drugs with
      fast clearance, fast diffusivity and low to intermediate cell binding; and (2)
      one dose is most effective for drugs with slow clearance, slow diffusivity or
      strong cell binding. Understanding the role of tissue transport when determining
      drug treatment schedules would improve the outcome of preclinical animal
      experiments and early clinical trials.

PMID- 29066116
TI  - Association between the 6-minute walk test and exercise confidence in patients
      with heart failure: A prospective observational study.
AB  - BACKGROUND: Exercise confidence predicts exercise adherence in heart failure (HF)
      patients. The association between simple tests of functional capacity on exercise
      confidence are not known. OBJECTIVES: To evaluate the association between a
      single 6-min walk test (6MWT) and exercise confidence in HF patients. METHODS:
      Observational study enrolling HF outpatients who completed the Cardiac Depression
      Scale and an Exercise Confidence Survey at baseline and following the 6MWT.
      Paired t-test was used to compare repeated-measures data, while Repeated Measures
      Analysis of Covariance was used for multivariate analysis. RESULTS: 106 HF
      patients were enrolled in the study (males, 82%; mean age, 64 +/- 12 years).
      Baseline Exercise Confidence was inversely associated with age (p < 0.01), NYHA
      class (p < 0.001), and depression (p < 0.001). The 6MWT was associated with an
      improvement in Exercise Confidence (F(1,92) = 5.0, p = 0.03) after adjustment for
      age, gender, HF duration, NYHA class and depression. CONCLUSIONS: The 6MWT is
      associated with improved exercise confidence in HF patients.

PMID- 29066115
TI  - Gender and racial differences in surgical outcomes among adult patients with
      acute heart failure.
AB  - BACKGROUND: Approximately three million U.S. adult women have heart failure (HF),
      increasing their risk of adverse perioperative outcomes. While gender and racial
      differences are reported in surgical outcomes, less is known about 30-day
      perioperative outcomes in HF patients. OBJECTIVES: To characterize and compare
      gender and racial differences in 30-day perioperative outcomes in adults with new
      or acute/worsening HF. METHODS: The 2012-2013 American College of Surgeons
      National Surgical Quality Improvement Program database of surgical patients (n =
      9458) with HF was analyzed. Logistic regression was used to adjust for gender and
      racial differences in baseline covariates. RESULTS: No gender difference in
      mortality (odds ratio = 0.922, 95% confidence interval = 0.0792-1.073, p = 0.294)
      was noted. Whites were more likely than Blacks to die 30 days after surgery (14%
      vs 9%, p < 0.001); after adjustment, Blacks were more likely to experience
      complications and be readmitted compared to Whites. CONCLUSIONS: There was no
      gender difference in mortality. White patients with HF were more likely to die
      after surgery than Black patients.

PMID- 29066117
TI  - Renal lymphomatous infiltration in patient with nefrotic syndrome.

PMID- 29066118
TI  - A de novo p.Arg756Cys mutation in ATP1A3 causes a distinct phenotype with
      prolonged weakness and encephalopathy triggered by fever.
AB  - Patients with a mutation at Arg756 in ATP1A3 have been known to exhibit a
      distinct phenotype, characterized by prolonged weakness and encephalopathy,
      triggered by febrile illness. With only eight reports published to date, more
      evidence is required to correlate clinical features with a mutation at Arg756.
      Here we report an additional case with an Arg756Cys mutation in ATP1A3. A four
      year-old boy showed mild developmental delay with recurrent paroxysmal episodes
      of weakness and encephalopathy from nine months of age. Motor deficits, which
      included bilateral hypotonia, ataxia, dysmetria, limb incoordination, dysarthria,
      choreoathetosis, and dystonia, were observed from one year and three months.
      Whole-exome sequencing detected a heterozygous de novo variant at c.2266C>T
      (p.Arg756Cys) in ATP1A3. The episodic course and clinical features of this case
      were consistent with previously reported cases with mutations at Arg756.
      Furthermore, his phenotype of marked ataxia was more similar to that of an
      Arg756Cys patient with relapsing encephalopathy and cerebellar ataxia syndrome,
      than to those with Arg756His and Arg756Leu mutations. This report therefore
      provides evidence of genotype-phenotype correlations in ATP1A3-related disorders
      as well as in patients with mutations at Arg756 in ATP1A3.

PMID- 29066119
TI  - Concurrent Chemoradiotherapy in Curatively Resected Gallbladder Carcinoma: A
      Propensity Score-Matched Analysis.
AB  - PURPOSE: To compare overall survival (OS) between patients receiving radical
      resection followed by concurrent chemoradiotherapy (S+CCRT) and patients
      receiving radical resection only (S) for advanced resectable gallbladder
      carcinoma (GBC). METHODS AND MATERIALS: Ninety-four GBC patients with stage pT2
      4, N0-1, and M0 consented to inclusion in a clinical database from June 2003 to
      July 2013. Patients who received S+CCRT were matched by propensity score with
      those who received S through nearest-neighbor matching, with a caliper width of
      0.2 to ensure similar baseline characteristics between each group. The effects of
      CCRT on OS and disease-free survival (DFS) were evaluated with Kaplan-Meier
      analysis. Cox proportional hazards regression was performed on the entire cohort.
      Adverse effects and oncologic outcomes were assessed. RESULTS: Seventy-eight
      patients with GBC (39 S+CCRT; 39 S) were matched according to propensity score;
      the 1-year, 3-year, and 5-year OS was 74.4%, 56.4%, and 42.4% for the S+CCRT
      group and 51.3%, 30.8%, and 17.9% for the S group. The median survival time was
      27 months (interquartile range [IQR], 12-58 months) for the S+CCRT group versus
      13 months (IQR, 5-30 months) for the S group (P=.004), with the 1-year and 3-year
      DFS being 59.0% versus 35.9% and 48.7% versus 13.5%, respectively, and the median
      DFS being 23 months (IQR, 8-57 months) versus 7 months (IQR, 4-23 months)
      (P=.004). CONCLUSIONS: The OS of matched patients with stage II-IVA GBC is
      significantly improved by CCRT. Radiation therapy combined with single-agent or
      dual-agent chemotherapy was feasible and well tolerated.

PMID- 29066121
TI  - Patterns of Intraosseous Recurrence After Stereotactic Body Radiation Therapy for
      Coxal Bone Metastasis.
AB  - PURPOSE: To analyze the detailed pattern of intraosseous failure after
      stereotactic body radiation therapy (SBRT) for coxal bone metastasis. METHODS AND
      MATERIALS: Patients treated with SBRT to coxal bone metastasis were identified by
      retrospective chart review. The SBRT doses were 30 Gy or 35 Gy in 5 fractions. A
      margin of 5 to 10 mm was added to the gross tumor volume to create the clinical
      target volume. We evaluated the presence or absence of intraosseous recurrence
      using magnetic resonance imaging. Intraosseous recurrences were assessed as "in
      field" or "marginal/out-of-field." In addition, we measured the distance between
      the center of the recurrent tumor and the nearest edge of the initial bone
      metastasis in cases of marginal/out-of-field recurrence. RESULTS: Seventeen
      patients treated for 17 coxal bone metastases were included. Median age was 64
      years (range, 48-79 years). Coxal lesions involved the ilium in 14 cases, pubis
      in 3, and ischium in 4 (3 lesions crossed over multiple regions). Patients most
      commonly had renal cell carcinoma (29.4%), followed by lung, hepatic cell, and
      colorectal cancers (23.5%, 11.8%, and 11.8%, respectively). Median follow-up
      after SBRT was 13 months (range, 2-44 months). Among all 17 cases, 7 cases
      developed 8 intraosseous recurrences, including in-field recurrence in 1 case and
      marginal/out-of-field recurrences in 7 cases. Median time to intraosseous
      recurrence was 10 months (range, 2-35 months). Among 7 cases with marginal/out-of
      field recurrence, mean distance to the center of the recurrent tumor from the
      nearest edge of the initial bone metastasis was 34 mm (range, 15-55 mm).
      CONCLUSIONS: Most recurrences were observed out-of-field in the same coxal bone.
      These results suggest that defining the optimal clinical target volume in SBRT
      for coxal bone metastasis to obtain sufficient local tumor control is difficult.

PMID- 29066120
TI  - Stereotactic Body Radiation Therapy as an Alternative to Transarterial
      Chemoembolization for Hepatocellular Carcinoma.
AB  - PURPOSE: To conduct a large single-institution comparison of transarterial
      chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) outcomes
      in similar groups of patients with hepatocellular carcinoma (HCC). METHODS AND
      MATERIALS: From 2006 to 2014, 209 patients with 1 to 2 tumors underwent TACE
      (n=84) to 114 tumors or image guided SBRT (n=125) to 173 tumors. Propensity score
      analysis with inverse probability of treatment weighting was used to compare
      outcomes between treatments while adjusting for imbalances in treatment
      assignment. Local control (LC), toxicity, and overall survival (OS) were
      retrospectively analyzed. RESULTS: The TACE and SBRT groups were similar with
      respect to the number of tumors treated per patient, underlying liver disease,
      and baseline liver function. Patients treated with SBRT were older (65 vs 61
      years, P=.01), had smaller tumors (2.3 vs 2.9 cm, P<.001), and less frequently
      underwent liver transplantation (8% vs 18%, P=.01). The 1- and 2-year LC favored
      SBRT: 97% and 91%, respectively, for SBRT and 47% and 23% for TACE (hazard ratio
      66.5, P<.001). For patients treated with TACE, higher alpha-fetoprotein (hazard
      ratio 1.11 per doubling, P=.008) and segmental portal vein thrombosis (hazard
      ratio 9.9, P<.001) were associated with worse LC. Predictors associated with LC
      after SBRT were not identified. Grade 3+ toxicity occurred after 13% and 8% of
      TACE and SBRT treatments, respectively (P=.05). There was no difference in OS
      between patients treated with TACE or SBRT. CONCLUSIONS: Stereotactic body
      radiation therapy is a safe alternative to TACE for 1 to 2 tumors and provides
      better LC, with no observed difference in OS. Prospective comparative trials of
      TACE and SBRT are warranted.

PMID- 29066122
TI  - Comparing the Effectiveness of Combined External Beam Radiation and Hyperthermia
      Versus External Beam Radiation Alone in Treating Patients With Painful Bony
      Metastases: A Phase 3 Prospective, Randomized, Controlled Trial.
AB  - PURPOSE: To compare the response, duration of pain relief, and time to achieve
      complete pain relief after radiation therapy (RT) with or without hyperthermia
      (HT) in patients with painful bony metastases. METHODS AND MATERIALS: Cancer
      patients with bony metastases and pain score >=4 on the Brief Pain Inventory
      (BPI) were randomized to RT of 30 Gy in 10 fractions combined with HT (RT + HT)
      versus RT alone. Hyperthermia was performed by the Thermotron RF-8, with
      maintenance of the target temperature for 40 minutes per treatment within 2 hours
      after RT, twice weekly for 2 weeks. Patients were stratified by lesion number
      (solitary or multiple), BPI score (4-6 vs 7-10), and primary site. The primary
      endpoint was complete response (CR) (BPI = 0 with no increase of analgesics)
      within 3 months after treatment. This study was registered with
      ClinicalTrials.gov. RESULTS: The study was terminated early after an interim
      analysis of 57 patients, 3 years after the first enrollment (November 2013 to
      November 2016): 29 patients in the RT + HT group and 28 patients in the RT-alone
      group. The CR rate at 3 months after treatment was 37.9% in the RT + HT group
      versus 7.1% in the RT-alone group (P=.006). The accumulated CR rate within 3
      months after treatment was 58.6% in the RT + HT group versus 32.1% in the RT
      alone group (P=.045). Median time to pain progression was 55 days in patients
      with CR (n=9) in the RT-alone group, whereas the endpoint was not reached during
      the 24-week follow-up in the RT + HT group (P<.01). CONCLUSIONS: The addition of
      HT to RT significantly increases the pain control rate and extends response
      duration compared with RT alone for painful bony metastases.

PMID- 29066124
TI  - Population-Based Study of Stereotactic Radiosurgery or Fractionated Stereotactic
      Radiation Therapy for Vestibular Schwannoma: Long-Term Outcomes and Toxicities.
AB  - PURPOSE: To examine long-term local control of vestibular schwannoma and side
      effects in patients treated with stereotactic radiosurgery (SRS) and fractionated
      stereotactic radiation therapy (SRT) in British Columbia. METHODS AND MATERIALS:
      From August 1998 to May 2009, 207 patients were treated with radiation therapy
      (RT) at British Columbia Cancer Agency. 136 (66%) received SRS, and 71 (34%)
      received SRT. Dose prescriptions were 50 Gy/25 fractions for SRT and 12 Gy/1
      fraction for SRS. Our multidisciplinary provincial neuro-stereotactic conference
      recommended SRT for tumors >3 cm and for patients with serviceable hearing
      (Gardner-Robertson classes I and II). RESULTS: Median follow-up was 7.7 years to
      the last MRI and 6.4 years to the last clinical assessment. Local control for SRS
      versus SRT was 94% versus 87% at 5 years and 90% versus 85% at 10 years (P=.2).
      Five- and 10-year actuarial rates of RT-induced trigeminal nerve dysfunction were
      25% and 25% after SRS, compared with 7% and 12% after SRT (P=.01). Five- and 10
      year actuarial rates of RT-induced facial nerve dysfunction were 15% and 15%
      after SRS, versus 13% and 15% after SRT (P=.93). In the 49 patients with
      serviceable hearing at baseline who were treated with SRT, hearing preservation
      was 55% at 3 years, 37% at 5 years, and 29% at 7 years. In multivariable
      analysis, better pretreatment ipsilateral pure tone average was significantly
      associated with hearing preservation (hazard ratio 1.03; 95% confidence interval
      1.00-1.07; P=.04). CONCLUSIONS: Both SRS and SRT provided excellent long-term
      local control of vestibular schwannoma. Stereotactic radiosurgery was associated
      with higher rates of trigeminal nerve dysfunction. Even with a fractionated
      course, hearing preservation declined steadily with long-term audiometric follow
      up.

PMID- 29066123
TI  - Deep-Inspiration Breath-Hold Radiation Therapy in Breast Cancer: A Word of
      Caution on the Dose to the Axillary Lymph Node Levels.
AB  - PURPOSE: To assess the differences in unintended regional nodal irradiation
      between free breathing (FB) and deep-inspiration breath-hold (DIBH) during
      tangential field irradiation. METHODS AND MATERIALS: We randomly chose 32
      patients from our database who underwent both DIBH and FB treatment planning.
      Contouring of the axillary lymph node levels (LI, LII, and LIII) was performed
      retrospectively according to the Radiation Therapy Oncology Group contouring
      atlas. We assessed the center of mass of each level and the planning target
      volume, as well as the dose distribution (Dmean, Dmedian, Dmax, Dmin, V30, and
      V40) in the lymph node levels I-III. Subsequently center of mass movement and
      dose changes due to deep inspiration treatment planning were calculated. RESULTS:
      All lymph node levels showed significant (P<.001) movement in anterior and
      cranial directions due to DIBH. The overall median movement (range) in the x
      (lateral), y (anterior-posterior), and z (cranio-caudal) directions was 0.1 cm
      (0.0-1.1 cm), 0.9 cm (0.1-2.0 cm), and 1.2 cm (0.0-2.6 cm), respectively.
      Movement of the planning target volume showed significant correlation (r=0.72,
      r=0.63, r=0.63; P<.05) with levels I-III. The average Dmean during FB/DIBH was as
      follows: LI 33.9 Gy/30.8 Gy (P<.001), LII 23.7 Gy/24.1 Gy (P=.74), and LIII 14.0
      Gy/15.6 Gy (P=.14). V30 was as follows: LI 63.8%/56.5% (P<.001), LII 44.6%/45.5%
      (P=.76), and LIII 24.2%/27.8% (P<.05). V40 was as follows: LI 58.9%/51.0%
      (P<.001), LII 39.3%/40.1% (P=.79), and LIII 20.4%/23.9% (P<.05). CONCLUSIONS:
      Deep-inspiration breath-hold results in a significant dose reduction in level I.
      Only minor changes in dose distribution were recorded for levels II and III.
      Thus, DIBH seems to have an impact on unintended regional nodal irradiation as
      compared with FB.

PMID- 29066125
TI  - Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A
      systematic review.
AB  - BACKGROUND AND PURPOSE: To perform a systematic review regarding the use of
      stereotactic ablative radiotherapy (SABR) for the re-irradiation of recurrent
      malignant disease within the pelvis, to guide the clinical implementation of this
      technique. MATERIAL AND METHODS: A systematic search strategy was adopted using
      the MEDLINE, EMBASE and Cochrane Library databases. RESULTS: 195 articles were
      identified, of which 17 were appropriate for inclusion. Studies were small and
      data largely retrospective. In total, 205 patients are reported to have received
      pelvic SABR re-irradiation. Dose and fractionation schedules and re-irradiated
      volumes are highly variable. Little information is provided regarding organ at
      risk constraints adopted in the re-irradiation setting. Treatment appears well
      tolerated overall, with nine grade 3 and six grade 4 toxicities amongst thirteen
      re-irradiated patients. Local control at one year ranged from 51% to 100%.
      Symptomatic improvements were also noted. CONCLUSIONS: For previously irradiated
      patients with recurrent pelvic disease, SABR re-irradiation could be a feasible
      intervention for those who otherwise have limited options. Evidence to support
      this technique is limited but shows initial promise. Based on the available
      literature, suggestions for a more formal SABR re-irradiation pathway are
      proposed. Prospective studies and a multidisciplinary approach are required to
      optimise future treatment.

PMID- 29066126
TI  - Diagnostic performance of a low dose triple rule-out CT angiography using SAFIRE
      in emergency department.
AB  - OBJECTIVES: To compare the diagnostic performance of "triple rule out" CT
      angiography (TRO-CTA) at 100kVp using sinogram affirmed iterative reconstruction
      (SAFIRE) with TRO-CTA at 120kVp using filtered back projection (FBP) in patients
      with acute chest pain. METHODS: Consecutive non-prepared patients from a single
      radiological emergency department, referred for acute chest pain evaluation with
      TRO-CTA, were randomly assigned to two different TRO-CTA protocols. Fifty
      patients (66% men; mean age, 66.6+/-19.0 [SD] years [range: 24-97years]) had TRO
      CTA at 120kVp with FBP and 97 patients (67% men; mean age, 62.8+/-17.9 [SD] years
      [range: 24-93years]) had TRO-CTA at 100kVp with SAFIRE. Two radiologists reviewed
      the TRO-CTA images for pathologic findings and degree of diagnostic confidence.
      Image noise, vessel attenuation value, signal-to-noise and contrast-to-noise
      ratios in five main thoracic arteries were measured for objective and subjective
      analysis. RESULTS: A total of 147 patients (98 men, 49 women; mean age, 64.7+/
      18.4 [SD] [range, 24-97years) were included with good diagnostic confidence and
      equivalent pathological findings between the two TRO-CTA protocols. Objective and
      subjective analysis were identical between protocols and radiologists, except for
      vessel attenuation in the ascending aorta (P=0.02) and image noise in the
      pulmonary trunk (P=0.04). The effective radiation dose decreased significantly by
      34% in the low dose TRO-CTA using SAFIRE protocol (5.7+/-2.7 vs 8.6+/-6.1mSv;
      P=4.7*10-6). CONCLUSIONS: Low dose TRO-CTA protocol using SAFIRE allows a high
      confidence diagnostic level with the benefit of a 34% radiation dose decrease
      compared with a standard TRO-CTA protocol using FBP.

PMID- 29066127
TI  - In vivo percutaneous microwave ablation in kidneys: Correlation with ex vivo data
      and ablation work.
AB  - PURPOSE: To compare diameters of in vivo microwave ablation (MWA) performed in
      swine kidneys with ex vivo diameters, and to correlate with ablation work (AW), a
      new metric reflecting total energy delivered. MATERIAL AND METHODS: Eighteen in
      vivo MWA were performed in 6 swine kidneys successively using one or two antennas
      (MicroThermX(r)). Ablation consisted in delivering power (45-120W) for 5
      15minutes. Ex vivo diameters were provided by the vendors and obtained on bovine
      liver tissue. AW was defined as the sum of (power)*(time)*(number of antennas)
      for all phases of an ablation (in kJoules). Kidneys were removed laparoscopically
      immediately after ablation. After sacrifice, ablations zones were evaluated
      macroscopically, and maximum diameters of the zones were recorded. Wilcoxon sum
      rank test and Pearson's correlation were used for comparisons. RESULTS: For a
      single antenna (n=12), the in vivo diameters ranged from 12 to 35mm, and 15-49mm
      for 2 antennas (n=6). The in vivo diameters remained shorter than ex vivo
      diameters by 8.6%+/-30.1 on 1 antenna and 11.7%+/-26.5 on 2 antennas (P=0.31 and
      0.44, respectively). AW ranged from 13.5 to 108kJ. Diameters increased linearly
      with AW both with 1 and 2 antennas, but only moderate correlations were observed
      (r=0.43 [95% confidence interval: -0.19; 0.81], P=0.16; and 0.57 [-0.44; 0.95],
      P=0.24, respectively). CONCLUSION: Although diameters after in vivo renal MWA
      increased linearly with AW, the moderate correlation and wide standard deviations
      observed may justify a careful imaging monitoring during treatment delivery and
      settings adaptation, if needed, for optimal ablation.

PMID- 29066128
TI  - Multimer of the antimicrobial peptide Mytichitin-A expressed in Chlamydomonas
      reinhardtii exerts a broader antibacterial spectrum and increased potency.
AB  - In this study, an antimicrobial peptide composed of three tandem repeats of
      Mytichitin-A (3 * Mytichitin-A) with a designed molecular weight of approximately
      25 kDa was expressed in the green alga Chlamydomonas reinhardtii. The yield of 3
      * Mytichitin-A reached 0.28% of the total soluble protein of the 3 * Mytichitin-A
      expressing transgenic cells and the expression level was stable following
      continuous passaging of the cells for six months. Compared to its natural and
      yeast-produced recombinant counterparts, which showed a very low level of growth
      inhibition of gram-negative bacteria, the 3 * Mytichitin-A inhibited the growth
      of gram-negative bacteria at a minimum inhibition concentration value ranging
      between 60 and 80 MUg/ml. The expressed 3 * Mytichitin-A did not show toxicity to
      HEK293 cells. Its bioactivity was hardly affected by temperature and pH but was
      impaired to some extent by the proteinase treatment. Taken together, our study
      showed that C. reinhardtii can be used as a cellular factory to produce bioactive
      Mytichitin-A in a multimeric format.

PMID- 29066130
TI  - Corrections.

PMID- 29066129
TI  - Acellular pertussis vaccines: where to go to?

PMID- 29066131
TI  - A genetically inactivated two-component acellular pertussis vaccine, alone or
      combined with tetanus and reduced-dose diphtheria vaccines, in adolescents: a
      phase 2/3, randomised controlled non-inferiority trial.
AB  - BACKGROUND: Increasing evidence shows that protection induced by acellular
      pertussis vaccines is short-lived, requiring repeated booster vaccination to
      control pertussis disease. We aimed to assess the safety and immunogenicity of a
      recombinant acellular pertussis vaccine containing genetically inactivated
      pertussis toxin and filamentous haemagglutinin, as either a monovalent vaccine
      (aP[PTgen/FHA]) or in combination with tetanus and reduced-dose diphtheria
      vaccines (TdaP[PTgen/FHA]), versus a licensed tetanus and reduced-dose diphtheria
      and acellular pertussis combination vaccine (Tdap). METHODS: We did this phase
      2/3, randomised controlled non-inferiority trial at two sites in Bangkok,
      Thailand. Healthy adolescents (aged 12-17 years) were randomly assigned (1:1:1),
      via a computer-generated randomisation list with block sizes of three, to receive
      one dose (0.5 mL) of aP(PTgen/FHA), TdaP(PTgen/FHA), or Tdap (comparator).
      Clinical research staff responsible for participant randomisation, vaccine
      preparation and administration, and accountability were aware of group
      allocation. However, allocation was concealed from all other site study staff,
      data management personnel, statisticians, laboratory staff, and study
      participants. The primary outcome was non-inferior immunogenicity of
      TdaP(PTgen/FHA) to Tdap based on seroconversion rates (a four-fold increase or
      more) for pertussis toxin and filamentous haemagglutinin IgG antibodies 28 days
      after vaccination, with a predefined 10% margin of equivalence. We did analysis
      by per protocol. This study is registered with the Thai Clinical Trial Registry,
      number TCTR20150703002. FINDINGS: Between July 6 and Aug 20, 2015, we allocated
      450 participants to receive one dose of TdaP(PTgen/FHA) (n=150), aP(PTgen/FHA)
      (n=150), or comparator Tdap (n=150). 28 days after vaccination, seroconversion
      rates for anti-pertussis toxin IgG were 96.6% (95% CI 93.8-99.5; n=144) in the
      TdaP(PTgen/FHA) group and 55.0% (47.1-63.0; n=82) in the comparator Tdap group
      (difference 41.6%, 95% CI 33.1-50.1; p<0.0001). Seroconversion rates for anti
      filamentous haemagglutinin were 82.6% (95% CI 76.5-88.6; n=123) in the
      TdaP(PTgen/FHA) group and 54.4% (46.4-62.4; n=81) in the comparator group
      (difference 28.2%, 95% CI 18.1-38.2 p<0.0001). 28 days after vaccination,
      seroconversion rates in the aP(PTgen/FHA) group were 96.0% (95% CI 92.8-99.1;
      n=142) for anti-pertussis toxin IgG and 93.2% (89.2-97.3; n=138) for anti
      filamentous haemagglutinin IgG. These findings support the non-inferior
      immunogenicity of TdaP(PTgen/FHA) over comparator Tdap. Reactogenicity and
      incidence of adverse events were similar between groups. INTERPRETATION: The new
      TdaP(PTgen/FHA) vaccine is safe and induces higher pertussis responses 28 days
      after vaccination than does the available licensed Tdap booster vaccine. Results
      of our trial led to the licensure of new acellular pertussis vaccines containing
      genetically inactivated pertussis toxin in Thailand. The availability of
      recombinant monovalent pertussis vaccines that induce high antibody responses
      provides the medical community and consumers with the opportunity to vaccinate
      against pertussis when immunisation against diphtheria and tetanus is not
      required or not desired. Studies are underway to pave the way for licensure
      studies of this acellular pertussis vaccine in other countries. FUNDING: BioNet
      Asia.

PMID- 29066132
TI  - The WHO public health approach to HIV treatment and care: looking back and
      looking ahead.
AB  - In 2006, WHO set forth its vision for a public health approach to delivering
      antiretroviral therapy. This approach has been broadly adopted in resource-poor
      settings and has provided the foundation for scaling up treatment to over 19.5
      million people. There is a global commitment to end the AIDS epidemic as a public
      health threat by 2030 and, to support this goal, there are opportunities to adapt
      the public health approach to meet the ensuing challenges. These challenges
      include the need to improve identification of people with HIV infection through
      expanded approaches to testing; further simplify and improve treatment and
      laboratory monitoring; adapt the public health approach to concentrated
      epidemics; and link HIV testing, treatment, and care to HIV prevention.
      Implementation of these key public health principles will bring countries closer
      to the goals of controlling the HIV epidemic and providing universal health
      coverage.

PMID- 29066133
TI  - Enhancement of Cricothyroidotomy Education Using a Novel Technique: Cadaver
      Autografting.
AB  - BACKGROUND: Cricothyroidotomy is a lifesaving procedure required in up to 2% of
      emergent airways. Emergency medicine training programs frequently instruct this
      procedure via cadaver training, but cadaver cost and availability limit the
      opportunity for all trainees to perform the critical initial skin incision.
      Cadaver autografting is a novel way to simulate all steps of the procedure.
      OBJECTIVE: Our aim was to determine whether the technique of autografting cadaver
      tissue improves the experience of cricothyroidotomy simulation education for
      emergency medicine trainees. The investigators hypothesized that autografted
      cadaver tissue would be a useful adjunct. METHODS: In this prospective crossover
      study, volunteers were randomized to first perform cricothyroidotomy on
      previously incised native neck tissue or on autografted tissue, and then vice
      versa. The autograft consisted of cadaver iliotibial band covered with lateral
      thigh skin and subcutaneous tissue to simulate cricothyroid membrane and native
      anterior neck anatomy. Volunteer emergency medicine residents and sub-interns
      were included. Twenty-seven residents and nine students participated. Outcomes
      were evaluated via Likert scale. RESULTS: Thirty of 36 (83%) participants agreed
      or strongly agreed that they preferred cadaver autografting to the previously
      incised native tissue. Thirty-two of 36 (89%) agreed or strongly agreed that
      cadaver autografting was useful vs. 23 of 36 (64%) who answered similarly
      regarding previously incised native tissue (p = 0.001). Twenty-six of 36 (72%)
      were more comfortable with cricothyroidotomy in the emergency department after
      using cadaver autografting vs. 19 of 36 (53%) after using the native tissue (p =
      0.003). CONCLUSIONS: Autografted cadaver tissue while simulating
      cricothyroidotomy was perceived to be a useful adjunct by the majority of
      participating emergency medicine trainees.

PMID- 29066134
TI  - Case Report: Cutaneous Metastasis of Lung Carcinoma.

PMID- 29066135
TI  - Need for refining successful revascularization in endovascular treatment of acute
      ischemic stroke: Data from real-world.
AB  - INTRODUCTION: Modified TICI (mTICI) score>=2b has been largely used as a
      definition of successful revascularization in acute stroke endovascular treatment
      (EVT). However, mTICI 2b encompasses a broad range of different revascularization
      states and its clinical relevance, comparing to mTICI 3, has been questioned. We
      aimed to compare clinical outcomes between these two reperfusion groups, in
      patients submitted to EVT for anterior circulation large-vessel occlusion, in a
      real-world setting. MATERIALS AND METHODS: Retrospective statistical analysis of
      our database of consecutive EVTs. RESULTS: Our study population of 178 patients
      has a mean age of 71years, 46.6% males, median baseline NIHSS of 17 and ASPECTS
      of 8. There were no statistically significant differences in baseline
      characteristics and interventional procedure data between groups. A significantly
      higher rate of mRS<=1 at 3months (OR=2.33, 95%CI 1.03-5.25) and lower rate of
      total (OR=0.18, 95%CI 0.06-0.53) and symptomatic intracranial hemorrhage
      (OR=0.08, 95%CI 0.01-0.74) was seen in mTICI 3 group. This group also showed non
      significant trend (adjusted p=0.071) toward higher percentages of mRS<=2 (71.8%
      versus 51.5%) and lower mortality at 3months (6.4% versus 19.1%). CONCLUSIONS: In
      accordance with previous reports from clinical trials, these real-world data
      suggest that is probably time to refine the definition of successful
      revascularization in acute stroke EVT.

PMID- 29066136
TI  - Ability of higenamine and related compounds to enhance glucose uptake in L6
      cells.
AB  - beta2-Adrenergic receptor (beta2AR) agonists are employed as bronchodilators to
      treat pulmonary disorders, but are attracting attention for their modulation of
      glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline
      present in several plant species and has beta2AR agonist activity, but the
      involvement of each functional groups in beta2AR agonist activity and its
      effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and
      norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known
      to be induced through beta2AR activation. Here, the ability to enhance glucose
      uptake of higenamine was compared with that of several methylated derivatives of
      higenamine or endogenous catecholamines. We found that: (i) the functional groups
      of higenamine except for the 4'-hydroxy group are required to enhance glucose
      uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with
      that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater
      ability to enhance glucose uptake compared with that of the R-isomer.

PMID- 29066137
TI  - Sustainable mechanical biological treatment of solid waste in urbanized areas
      with low recycling rates.
AB  - Landfill is still the main technological facility used to treat and dispose
      municipal solid waste (MSW) worldwide. In developing countries, final dumping is
      applied without environmental monitoring and soil protection since solid waste is
      mostly sent to open dump sites while, in Europe, landfilling is considered as the
      last option since reverse logistic approaches or energy recovery are generally
      encouraged. However, many regions within the European Union continue to dispose
      of MSW to landfill, since modern facilities have not been introduced owing to
      unreliable regulations or financial sustainability. In this paper, final disposal
      activities and pre-treatment operations in an area in southern Italy are
      discussed, where final disposal is still the main option for treating MSW and the
      recycling rate is still low. Mechanical biological treatment (MBT) facilities are
      examined in order to evaluate the organic stabilization practices applied for MSW
      and the efficiencies in refuse derived fuel production, organic waste
      stabilization and mass reduction. Implementing MBT before landfilling the
      environmental impact and waste mass are reduced, up to 30%, since organic
      fractions are stabilized resulting an oxygen uptake rate less than 1600 mgO2 h-1
      kg-1VS, and inorganic materials are exploited. Based on experimental data, this
      work examines MBT application in contexts where recycling and recovery activities
      have not been fully developed. The evidence of this study led to state that the
      introduction of MBT facilities is recommended for developing regions with high
      putrescible waste production in order to decrease environmental pollution and
      enhance human healthy.

PMID- 29066138
TI  - Evidence on Synthesized Two-dimensional Mammography Versus Digital Mammography
      When Using Tomosynthesis (Three-dimensional Mammography) for Population Breast
      Cancer Screening.
AB  - One limitation of using digital breast tomosynthesis (3-dimensional [3D]
      mammography) technology with conventional (2-dimensional [2D]) mammography for
      breast cancer (BC) screening is the increased radiation dose from dual
      acquisitions. To resolve this problem, synthesized 2D (s2D) reconstruction images
      similar to 2D mammography were developed using tomosynthesis acquisitions. The
      present review summarizes the evidence for s2D versus digital mammography (2D)
      when using tomosynthesis (3D) for BC screening to address whether using s2D
      instead of 2D (alongside 3D) will yield similar detection measures. Comparative
      population screening studies have provided consistent evidence that cancer
      detection rates do not differ between integrated 2D/3D (range, 5.45-8.5/1000
      screens) and s2D/3D (range, 5.03-8.8/1000 screens). Also, although the recall
      measures were relatively heterogeneous across included studies, little difference
      was found between the 2 modalities. The mean glandular dose for s2D/3D was 55% to
      58% of that for 2D/3D. In the context of BC screening, s2D/3D involves
      substantially less radiation than 2D/3D and provides similar detection measures.
      Thus, consideration of transitioning to tomosynthesis screening should aim to use
      s2D/3D to minimize harm.

PMID- 29066139
TI  - Role of BI-RADS Ultrasound Subcategories 4A to 4C in Predicting Breast Cancer.
AB  - BACKGROUND: The Breast Imaging Reporting and Data System (BI-RADS) ultrasound
      (US) categorization revised in 2013 by the American College of Radiology resulted
      in unquestionable standardization of reports and confirmed category 3 and 5 as
      benign and malignant lesions, respectively. In contrast, suspected images
      (category 4) have subcategorization criteria, although theses have been detailed
      difficult to apply. The aim of the present study was to determine the role of the
      US 4A to 4C BI-RADS subcategories in predicting malignancy. PATIENTS AND METHODS:
      We performed a cross-sectional study of diagnostic tests to estimate the
      performance of the US BI-RADS categorization to clearly differentiate benign from
      malignant lesions. A total of 975 US examinations performed at the Hospital
      Femina, Grupo Hospitalar Conceicao teaching hospitals from January 2012 through
      March 2015 were included in the present study. The US BI-RADS lexicon was used to
      classify the examination findings. Suspicious lesions underwent core needle
      biopsy, and the US and histology reports were compared to determine the
      performance using receiver operating characteristic curves. RESULTS: Overall, the
      BI-RADS US categorization showed good discriminating accuracy with a receiver
      operating characteristic curve of 91% (95% confidence interval [CI], 88%-93%).
      However, BI-RADS subcategory 4b had a positive predictive value of 25% (95% CI,
      20%-31%) and subcategory 4A had a positive predictive value of only 6% (95% CI,
      3.5%-9.8%). CONCLUSION: Our results have shown that US BI-RADS subcategories 4A
      and 4B are clearly unfit for use in screening tests, because they cannot rule out
      the need for biopsy. Therefore, management will not be improved by
      subcategorizing category 4, because all suspicious lesions will still require
      definite biopsy.

PMID- 29066141
TI  - Evaluation of a shoe sole UVC device to reduce pathogen colonization on floors,
      surfaces and patients.
AB  - BACKGROUND: An ultraviolet C (UVC) decontamination device that delivers
      germicidal UVC radiation to the soles of shoes has become available recently.
      AIM: To demonstrate that shoe soles can be vectors for healthcare-associated
      infection, and to investigate if a UVC shoe sole decontamination device would
      decrease this risk effectively. METHODOLOGY: Three bacterial strains
      (Staphylococcus aureus, Enterococcus faecalis and Escherichia coli) and a non
      toxigenic strain of Clostridium difficile were spiked on to standardized rubber
      soled shoe soles and then selected at random for UVC exposure or no UVC exposure.
      Experiments were performed to test the efficacy of the UVC device to
      decontaminate shoe soles and flooring. E. faecalis was spiked on to shoes to
      assess colonization of a simulated healthcare environment and patient. RESULTS:
      The UVC device decreased shoe sole contamination significantly for all tested
      bacterial species, and decreased floor contamination significantly for all floor
      types and species tested (P<0.01 for all experiments). The log10 reduction was
      the highest for E. coli (mean+/-standard deviation 2.6+/-0.79), followed by E.
      faecalis (2.19+/-0.68), S. aureus (1.74+/-0.88) and C. difficile (0.42+/-0.54)
      (P<0.0001 for all analyses). Exposure of shoe soles to the UVC device decreased
      contamination significantly (mean log10 reduction 2.79+/-1.25; P<0.0001).
      Proportions of samples from furniture, bed and patient dummy samples decreased
      from 96-100% positive in controls to 5-8% positive in UVC device experiments
      (P<0.0001 for all analyses). CONCLUSION: A UVC decontamination device was shown
      to reduce the colony-forming unit counts of relevant pathogenic organisms from
      shoe soles with subsequent decreased colonization of floors, healthcare
      equipment, furniture, beds and a patient dummy.

PMID- 29066140
TI  - Vancomycin-resistant enterococci isolates colonizing and infecting haematology
      patients: clonality, and virulence and resistance profile.
AB  - BACKGROUND: Vancomycin-resistant enterococci (VRE) are an important agent of
      colonization and infection in haematology patients. However, the role of
      virulence on VRE colonization and infection is controversial. AIM: To
      characterize the lineage, virulence and resistance profile of VRE infection and
      colonization isolates; as well as their impact on outcome of haematology patients
      using a regression logistic model. METHODS: Eighty-six isolates (80 Enterococcus
      faecium and six E. faecalis) from 76 patients were evaluated. Polymerase chain
      reaction for resistance and virulence genes, and pulsed-field gel electrophoresis
      and whole genome sequencing of the major clusters, were performed. Bivariate and
      multivariate analyses were carried out to evaluate the role of virulence genes on
      outcome. FINDINGS: All isolates harboured the vanA gene. Regarding the virulence
      genes, 96.5% of isolates were positive for esp, 69.8% for gelE and asa1 genes.
      VRE infection isolates were more virulent than colonization isolates and
      harboured more often the gelE gene (P = 0.008). Infections caused by VRE carrying
      asa1 gene resulted more frequently in death (P = 0.004), but only the predominant
      clone remained as protector in the multivariate model. The E. faecium strains
      were assigned to seven STs (ST78, ST412, ST478, ST792, ST896, ST987, ST963) that
      belonged to CC17. The E. faecalis sequenced belonged to ST9 (CC9). CONCLUSION: E.
      faecium was predominant, and infection isolates were more virulent than
      colonization isolates and harboured more often the gene gelE. Infections caused
      by VRE carrying the asa1 gene appeared to be associated with a fatal outcome.

PMID- 29066142
TI  - Internet as a source of medicines information (MI) among frequent internet users.
AB  - BACKGROUND: The internet is widely and increasingly used to search for health
      information. Previous studies have focused mainly on health information on the
      internet and not specifically on medicines information (MI). OBJECTIVES: The aim
      of this study was to explore the internet as a source of MI compared to other
      sources of MI; to identify those who use the internet as a source of MI; and to
      describe patterns of use of the internet as a source of MI. METHODS: A cross
      sectional design employed a web-based questionnaire posted by patients' and other
      organizations as well as pharmacies on their websites during six weeks in the
      beginning of 2014. Logistic regression analysis was used to assess associations
      of background variables to the use of different MI sources. RESULTS: The most
      frequently used MI sources among respondents (n = 2489) were package leaflets
      (90%), pharmacists (83%), physicians (72%), and the internet (68%). According to
      a multivariate analysis, internet use for MI was associated with female gender,
      age <65 years, higher education, daily use of the internet, and continuous use of
      vitamins or herbals. MI was most commonly searched from a Finnish health portal
      (56%) and websites of pharmacies (41%). Of the respondents, nearly half (43%)
      used search engines to find information from the internet. The names of the
      medicinal product, symptom or disease were the most commonly used search terms.
      CONCLUSIONS: Well-educated, young women tend to search MI on the internet. Health
      care professionals should discuss reliable MI websites and tools that can help
      patients evaluate the reliability of information.

PMID- 29066143
TI  - Corrigendum to "Genetic analysis of meat quality traits in maternal lines of
      rabbit and their diallel cross" [Meat Science 131 (2017) 1-8].

PMID- 29066144
TI  - The Value of Echocardiography in Unexpected Valve Disease in a Patient With
      Ischemic Cardiomyopathy: Less Is Not Always the Right Answer.

PMID- 29066146
TI  - Sedation Versus General Anesthesia for TAVR: Where Do We Go From Here?

PMID- 29066145
TI  - Intravenous Acetaminophen Does Not Decrease Persistent Surgical Pain After
      Cardiac Surgery.
AB  - OBJECTIVE: The authors investigated the hypothesis that perioperative
      acetaminophen reduces incisional pain at 30 and 90 days. DESIGN: This was a
      prospective, randomized, double-blind trial. SETTING: Tertiary-care hospital
      (single center) cardiac surgery unit. PARTICIPANTS: Patients undergoing cardiac
      surgery via median sternotomy. INTERVENTIONS: Patients were assigned randomly to
      intravenous (IV) acetaminophen or IV placebo. Patients were given 4 doses of 1 g
      of IV acetaminophen or an equal volume of saline placebo over 15 minutes every 6
      hours for 24 hours starting in the operating room after sternal closure.
      MEASUREMENTS AND MAIN RESULTS: Study participants were assessed by phone for
      incisional pain severity 30 and 90 days after surgery. Those reporting any
      incisional pain were asked to complete the Neuropathic Pain Questionnaire-Short
      Form and the modified Brief Pain Inventory. Patients were compared on 30- and 90
      day incisional pain severity using separate multivariable linear regression
      models. IV acetaminophen had no effect on 30- and 90-day incisional pain, with an
      estimated difference in means (confidence interval) of 0.06 (-0.87 to 0.99) at 30
      days (p = 0.88) and 0.07 (-0.71 to 0.86) at 90 days (p = 0.83). Low pain
      severity, neuropathic pain, and interference at both 30 and 90 days after
      surgery, regardless of treatment group, were observed. CONCLUSIONS: IV
      acetaminophen did not reduce the incidence or intensity of incisional pain at 30
      days and 90 days after surgery.

PMID- 29066147
TI  - Heart-Type Fatty Acid Binding Protein and High-Dose Methylprednisolone in
      Pediatric Cardiac Surgery.
AB  - OBJECTIVES: Corticosteroids possess cardioprotection in experimental cardiac
      ischemia/reperfusion. The authors hypothesized that if cardioprotection of
      corticosteroids occured during pediatric cardiac surgery, then methylprednisolone
      used in cardiopulmonary bypass prime would reduce postoperative concentrations of
      heart-type fatty-acid-binding protein, a cardiac biomarker. DESIGN: A double
      blind, placebo-controlled, randomized clinical trial. SETTING: Operating room and
      pediatric intensive care unit of a university hospital. PARTICIPANTS: Forty-five
      infants and young children undergoing ventricular or atrioventricular septal
      defect correction. INTERVENTIONS: The patients received one of the following: 30
      mg/kg of methylprednisolone intravenously after anesthesia induction (n = 15), 30
      mg/kg of methylprednisolone in cardiopulmonary bypass prime solution (n = 15), or
      placebo (n = 15). MEASUREMENTS AND MAIN RESULTS: Plasma heart-type fatty-acid
      binding protein (hFABP) was measured. Preoperatively, hFABP did not differ among
      the study groups. Methylprednisolone administered preoperatively and in the
      cardiopulmonary bypass prime solution reduced hFABP by 44% (p = 0.010) and 38% (p
      = 0.033) 6 hours postoperatively. hFABP significantly correlated with concomitant
      troponin T after protamine administration (R = 0.811, p < 0.001) and 6 hours
      postoperatively (R = 0.806, p < 0.001). CONCLUSIONS: Methylprednisolone in
      cardiopulmonary bypass prime solution administered only a few minutes before
      cardiac ischemia confered cardioprotection of the same magnitude as preoperative
      methylprednisolone as indicated by hFABP concentrations. Rapid cardioprotective
      actions of corticosteroids in pediatric heart surgery observed previously
      experimentally may have occurred.

PMID- 29066148
TI  - Occam's Foil: When One Diagnosis Isn't Enough.

PMID- 29066149
TI  - The Congenital Cardiac Anesthesia Society: An Update on the First Twelve Years.
AB  - The Congenital Cardiac Anesthesia Society is an international body instituted for
      collaboration among parties with interest in the perioepartive care of patients
      with congenial heart disease. This report is a review and update on the first 12
      years of this society.

PMID- 29066150
TI  - The Psychosocial Experiences and Needs of Children Undergoing Surgery and Their
      Parents: A Systematic Review.
AB  - INTRODUCTION: Surgery in children can be difficult for patients and parents. We
      aimed to summarize pediatric patients' and parents' psychosocial experiences and
      needs in surgery. METHOD: We used the Ovid search engine and screened 877
      abstracts across three databases to extract data on pediatric patients' and
      parents' surgical experiences. RESULTS: Our search yielded 11 eligible studies
      representing 1,307 children undergoing surgery and their parents. Children's
      adverse experiences included psychological and behavioral changes before, during,
      and after surgery (e.g., anxiety, eating disturbances). Parents commonly
      experienced psychological distress. Children's needs related to medical and
      health care services, whereas parents had high information needs. DISCUSSION:
      Children's adverse experiences can negatively affect medical outcomes. Children's
      experiences are inextricably linked to their parents' and can become negatively
      affected by their parents' adverse experiences. Patients and parents with
      previous hospitalizations and surgeries had worse surgical experiences,
      highlighting further research in the context of chronic illness.

PMID- 29066151
TI  - Comparison of thoracic endovascular aortic repair, open surgery and best medical
      treatment for type B aortic dissection: A meta-analysis.
AB  - BACKGROUND: Treatments of type B aortic dissection (TBAD) include thoracic
      endovascular aortic repair (TEVAR), best medical treatment (BMT) and open surgery
      (OS). This meta-analysis was to compare these three strategies to evaluate which
      provides best outcomes. METHODS: We searched clinical trials that compared
      treatment strategies for TBAD. The outcomes measures were 30-day/in-hospital
      mortality, long-term survival rate, paraplegia or paraparesis, renal failure,
      rupture, stroke, late re-intervention, late rupture and aneurismal
      dilatation/expansion. RESULTS: Sixteen control trials covering 10,307 patients
      were evaluated. Meta-analysis showed that TEVAR provides preferable long-term
      survival rate (HR=0.71; 95% CI: 0.52-0.95), lower rate of late re-intervention
      (OR=0.33; 95% CI: 0.13-0.85), late rupture (OR=0.21; 95% CI: 0.10-0.43) and late
      aneurismal dilatation/expansion (OR=0.15; 95% CI: 0.04-0.63) compared with BMT.
      However, TEVAR seemed to be associated with higher stroke rate than BMT (OR=1.65;
      95% CI: 1.21-2.23). 30-day/in-hospital mortality appeared to be lower in TEVAR
      (OR=0.49; 95% CI: 0.29-0.81) when compared with OS. In addition, OS induced
      higher 30-day/in-hospital mortality compared with BMT (OR=3.95, 95% CI: 1.56
      10.02). CONCLUSIONS: Our study shows that TEVAR may be favorable in long-term
      outcomes and effectively provide morphologic advantages compared to BMT. However,
      there is a need for prophylactic measures against stroke in TEVAR. OS seems to be
      inferior to TEVAR both in short-term and long-term outcomes. Further studies
      especially randomized clinical trials are needed to comprehensively compare the
      efficacy between TEVAR and BMT.

PMID- 29066152
TI  - Extracellular vesicles are integral and functional components of the
      extracellular matrix.
AB  - Extracellular vesicles (EV) are small plasma membrane-derived particles released
      into the extracellular space by virtually all cell types. Recently, EV have
      received increased interest because of their capability to carry nucleic acids,
      proteins, lipids and signaling molecules and to transfer their cargo into the
      target cells. Less attention has been paid to their role in modifying the
      composition of the extracellular matrix (ECM), either directly or indirectly via
      regulating the ability of target cells to synthesize or degrade matrix molecules.
      Based on recent results, EV can be considered one of the structural and
      functional components of the ECM that participate in matrix organization,
      regulation of cells within it, and in determining the physical properties of soft
      connective tissues, bone, cartilage and dentin. This review addresses the
      relevance of EV as specific modulators of the ECM, such as during the assembly
      and disassembly of the molecular network, signaling through the ECM and formation
      of niches suitable for tissue regeneration, inflammation and tumor progression.
      Finally, we assess the potential of these aspects of EV biology to translational
      medicine.

PMID- 29066153
TI  - Extracellular matrix alterations in senescent cells and their significance in
      tissue homeostasis.
AB  - Normal cells after a defined number of successive divisions or after exposure to
      genotoxic stresses are becoming senescent, characterized by a permanent growth
      arrest. In addition, they secrete increased levels of pro-inflammatory and
      catabolic mediators, collectively termed "senescence-associated secretory
      phenotype". Furthermore, senescent cells exhibit an altered expression and
      organization of many extracellular matrix components, leading to specific
      remodeling of their microenvironment. In this review we present the current
      knowledge on extracellular matrix alterations associated with cellular senescence
      and critically discuss certain characteristic examples, highlighting the
      ambiguous role of senescent cells in the homeostasis of various tissues under
      both normal and pathologic conditions.

PMID- 29066154
TI  - Production of the recombinant antimicrobial peptide UBI18-35 in Escherichia coli.
AB  - Radiolabeled peptides derived from ubiquicidine (UBI) are of great interest for
      early and highly accurate scintigraphic detection and differentiation of
      infection and sterile inflammation. In the present work the recombinant
      antimicrobial peptide UBI18-35 - a fragment of the human natural cationic peptide
      ubiquicidine - was produced in Escherichia coli for the first time. The insoluble
      expression of the peptide in fusion with ketosteroid isomerase provided high
      yield, about 6 mg of UBI18-35 per liter. We developed an approach to produce the
      antimicrobial peptide UBI18-35, that encompasses inclusion body isolation and
      size exclusion chromatography. This method could be the basis for industrial
      biotechnological production of diagnostic system components that are in high
      demand.

PMID- 29066155
TI  - Efficient solubilization and purification of highly insoluble membrane proteins
      expressed as inclusion bodies using perfluorooctanoic acid.
AB  - The purification of membrane proteins can be challenging due to their low
      solubility in conventional detergents and/or chaotropic solutions. The
      introduction of fusion systems that promote the formation of inclusion bodies has
      facilitated the over-expression of membrane proteins. In this protocol, we
      describe the use of perfluorooctanoic acid (PFOA) as an aid in the purification
      of highly hydrophobic membrane proteins expressed as inclusion bodies. The
      advantage of utilizing PFOA is threefold: first, PFOA is able to reliably
      solubilize inclusion bodies, second, PFOA is compatible with nickel affinity
      chromatography, and third, PFOA can be efficiently dialyzed away to produce a
      detergent free sample. To demonstrate the utility of employing PFOA, we expressed
      and purified a segment of the extremely hydrophobic membrane protein caveolin-1.

PMID- 29066156
TI  - Gestational diabetes mellitus screening according to Carpenter-Coustan and IADPSG
      criteria: A 7-year follow-up of prevalence, treatment and neonatal complications
      at a Belgian general hospital.

PMID- 29066157
TI  - Relationship between optical coherence tomography-defined in-stent
      neoatherosclerosis and out-stent arterial remodeling assessed by serial
      intravascular ultrasound examinations in late and very late drug-eluting stent
      failure.
AB  - BACKGROUND: Little is known regarding the association between chronological out
      stent vessel remodeling and in-stent tissue characteristics of drug-eluting stent
      (DES) failure. We aimed to evaluate the relationship between serial vessel
      remodeling after DES implantation and neoatherosclerosis (NA) assessed by optical
      coherence tomography (OCT) in patients with DES failure. METHODS: Forty-eight
      patients with late and very late stent failure after DES implantation, who
      underwent intravascular ultrasound (IVUS) at both the initial percutaneous
      coronary intervention and the time of stent failure and OCT imaging at the time
      of stent failure, were retrospectively investigated. NA on OCT was defined as
      neointimal formation with the presence of lipids or calcification inside the
      stents. Lesions were divided into two groups: those with NA and those without NA
      (NA: n=21; non-NA: n=27). From the serial IVUS examinations, external elastic
      membrane (EEM) volume and out-stent plaque volume were normalized by stent length
      and their changes were compared between the two groups. RESULTS: The NA group
      showed older stent age [median, 5.1 years (IQR, 4.8-8.3) vs 1.4 years (IQR, 0.8
      4.5); p<0.01] and more prevalent sirolimus-eluting stents (SES; 81.0% vs. 29.6%;
      p<0.01). IVUS findings of the NA group showed a greater serial increase in both
      normalized EEM volume and normalized out-stent plaque volume (OSPVI) [1.05 (0.41
      1.90) vs. 0.11 (-0.64 to 0.80) mm2; p<0.01; and 0.88 (0.57-1.98) vs. 0.12 (-0.41
      to 0.78) mm2; p<0.01]. On multivariate analysis, percentage change in OSPVI (OR,
      1.07; 95% CI, 1.01-1.14; p=0.02) and SES (OR, 9.78; 95% CI, 2.20-43.40; p<0.01)
      remained independent predictors of NA. CONCLUSIONS: NA in late and very late DES
      failure was associated with out-stent positive vessel remodeling. In addition to
      SES, out-stent progressive positive remodeling may help predict NA in late and
      very late DES failure.

PMID- 29066158
TI  - Learning style preferences of Australian accelerated postgraduate pre
      registration nursing students: A cross-sectional survey.
AB  - Graduate entry programs leading to registration are gaining momentum in nursing.
      These programs attract student cohorts with professional, cultural, gender and
      age diversity. As a consequence of this diversity, such accelerated programs
      challenge traditional pedagogical methods used in nursing and require different
      approaches. To date, however, there has been limited research on the learning
      styles of students undertaking these programs to inform academics involved in
      their delivery. Kolb's Experiential Learning model has been used widely in a
      variety of educational settings because it is based on the theory of experiential
      learning. More recently VARK (Visual, Aural, Read/write and Kinaesthetic) model
      has become popular. The aim of this study was to investigate the learning styles
      of two cohorts of graduate entry nursing students undertaking an accelerated
      masters-level program. This was a cross-sectional survey of two cohorts of Master
      of Nursing Practice students enrolled at a large Australian university. The
      students were more inclined toward converging (practical) and least toward
      concrete experience (experiencing) learning styles. The majority of students were
      more inclined toward kinaesthetic and least toward aural learning style. Findings
      have implications for academics engaged in teaching graduate entry nursing
      students.

PMID- 29066159
TI  - Effects of fish oil-derived fatty acids on suboptimal cardiovascular health: A
      multicenter, randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND AND AIMS: Suboptimal health and metabolic disorders are common in the
      general population. Both are related to cardiovascular disease. Suboptimal
      cardiovascular health is defined by the presence of both suboptimal health and
      metabolic disorders. The aim of the study was to investigate the potential
      benefit of n-3 long-chain polyunsaturated fatty acids (LCPUFA) in participants
      with suboptimal cardiovascular health. METHODS AND RESULTS: A total of 422
      participants with suboptimal cardiovascular health, from two clinics in China,
      were enrolled from September 2014 to April 2015. All the enrolled participants
      were randomly assigned to receive 4 g/d of fish oil or placebo for three months.
      Suboptimal health was defined using an accepted questionnaire. Metabolic
      disorders were defined as one or more abnormalities in blood pressure, fasting
      plasma glucose, blood lipids, and body mass index (BMI). After treatment, the
      mean BMI fell significantly more in the n-3 LCPUFA group than in the placebo
      group (-0.29 +/- 0.06 kg/m2 vs. -0.02 +/- 0.06 kg/m2, P = 0.003). Similar results
      were found in the changes of suboptimal health status and suboptimal
      cardiovascular health status (P < 0.05 for all). In a multivariate analysis, the
      n-3 LCPUFA group was 5.44 (1.15, 25.67) times more likely to have optimal
      cardiovascular health status after treatment. CONCLUSIONS: n-3 LCPUFA intake
      improved suboptimal cardiovascular health in this placebo-controlled, randomized,
      double-blind trial. TRIAL REGISTRATION: This study is registered at
      www.clinicaltrials.govNCT02103517.

PMID- 29066161
TI  - Proton craniospinal irradiation during the third trimester of pregnancy.

PMID- 29066160
TI  - Non-motor symptoms and quality of life in dopa-responsive dystonia patients.
AB  - BACKGROUND: In patients with GTP-cyclohydrolase deficient dopa-responsive
      dystonia (DRD) the occurrence of associated non-motor symptoms (NMS) is to be
      expected. Earlier studies report conflicting results with regard to the nature
      and severity of NMS. The aim of our study was to investigate the prevalence of
      psychiatric disorders, sleep problems, fatigue and health-related quality of life
      (HR-QoL) in a Dutch DRD cohort. METHODS: Clinical characteristics, motor
      symptoms, type and severity of psychiatric co-morbidity, sleep problems, fatigue
      and HR-QoL were assessed in DRD patients with a confirmed GCH1 mutation and
      matched controls. RESULTS: Twenty-eight patients were included (18 adults and 10
      children), from 10 families. Dystonia symptoms were well-controlled in all
      patients. According to the DSM IV patients significantly more often met the
      criteria for a lifetime psychiatric disorder than controls (61% vs. 29%, p <
      0.05). In particular the frequencies of generalized anxiety and agoraphobia were
      higher in patients (both 29% vs. 4%, p < 0.05). Patients scored significantly
      higher on daytime sleepiness than controls (ESS, 11.2 vs 5.7, p < 0.05). Adult
      patients had significantly lower scores on the mental component of the HR-QoL (47
      vs. 54, p < 0.05) than controls mainly associated with (worse) quality of sleep.
      CONCLUSION: NMS were highly prevalent in our cohort of DRD patients, despite
      adequate treatment of motor symptoms. Our findings support the accumulating
      evidence of an important non-motor phenotype in DRD, with possible involvement of
      serotonergic mechanisms. This highlights the need to address NMS and the
      underlying neurobiology in patients with DRD.

PMID- 29066162
TI  - Two States of Myeloma Stem Cells.
AB  - The identity of so-called malignant stem cells in multiple myeloma has long been
      controversial. However, it is now appreciated that a small population of myeloma
      cells has a stem-like capacity for self-renewal and resides within the population
      of recognizable myeloma plasma cells, although whether these cells are quiescent
      or proliferative remains unresolved. It is also now accepted that subpopulations
      of myeloma plasma cells alternate bidirectionally and dynamically between
      immature and mature phenotypes, and both subpopulations are capable of
      clonogenicity in vitro and in animal models. Mounting evidence suggests that in
      multiple myeloma, small populations of quiescent myeloma stem cells behave as
      tumor-initiating cells as a result of their interaction with the endosteal bone
      marrow niche. However, a different, small population of proliferative myeloma
      stem cells produces the tumor bulk, and this population is likely responsible for
      the emergence of evolved subclones. A cellular-based plasticity model in which 2
      states of stem-like cell compartments-quiescent and proliferative-exist
      simultaneously and are regulated dynamically by the microenvironment,
      epigenetics, and genetic aberrations may explain various clinical scenarios and
      the lack of consensus among some reported studies.

PMID- 29066164
TI  - Eculizumab: a treatment option for myasthenia gravis?

PMID- 29066165
TI  - Stem Cell Secretome and Its Effect on Cellular Mechanisms Relevant to Wound
      Healing.
AB  - Stem cells introduced to site of injury primarily act via indirect paracrine
      effects rather than direct cell replacement of damaged cells. This gives rise to
      understanding the stem cell secretome. In this study, in vitro studies
      demonstrate that the secretome activates the PI3K/Akt or FAK/ERK1/2 signaling
      cascades and subsequently enhances the proliferative and migratory abilities of
      various types of skin cells, such as fibroblasts, keratinocytes, and vascular
      epithelial cells, ultimately accelerating wound contraction. Indeed, inhibition
      of these signaling pathways with synthetic inhibitors resulted in the disruption
      of secretome-induced beneficial effects on various skin cells. In addition, major
      components of the stem cell secretome (EGF, basic FGF, and HGF) may be
      responsible for the acceleration of wound contraction. Stimulatory effects of
      these three prominent factors on wound contraction are achieved through the
      upregulation of PI3K/Akt or FAK/ERK1/2 activity. Overall, we lay the rationale
      for using the stem cell secretome in promoting wound contraction. In vivo wound
      healing studies are warranted to test the significance of our in vitro findings.

PMID- 29066167
TI  - The effects of medication use in transcranial direct current stimulation: A brief
      review.
AB  - BACKGROUND: There has been increased interest in the potential use of
      transcranial direct current stimulation (tDCS) as treatment for multiple
      conditions including depression, pain, and cognitive impairment. However, few
      studies account for the possible influence of comorbid medications when
      conducting tDCS research. OBJECTIVE/HYPOTHESIS: This literature review was
      conducted to examine what is currently known about the impact of medications on
      tDCS, provide recommendations for future research practices, and highlight areas
      where more research is needed. METHODS: Key terms were searched in PubMed and Web
      of Science to identify studies that examine the impact of medication on tDCS
      effects in adults. Relevant papers' reference lists were also reviewed for
      thoroughness. Studies examined the effects of medication on 1 mA tDCS delivered
      to M1 (motor) and orbit/supraorbital (SO) area. All studies measured the effects
      of tDCS via MEP TMS paradigm. RESULTS: Results of the literature review suggest
      multiple classes of medications, including sodium and calcium channel blockers,
      and medications that influence various neurotransmitter systems (GABA, dopamine,
      serotonin, etc.) may all impact tDCS effects on tissue excitability. CONCLUSIONS:
      Research to date suggests multiple classes of medications may impact tDCS
      effects. These results highlight the importance of documenting medication use in
      research subjects and carefully considering what types of medications should be
      allowed into tDCS trials. Many questions still remain regarding the exact
      mechanisms of action for tDCS and how various parameters (medication dosages,
      tDCS stimulation intensity, etc.) may further impact the effects of medications
      on tDCS.

PMID- 29066169
TI  - Genotypes of IFIH1 and IFIT5 in seven chicken breeds indicated artificial
      selection for commercial traits influenced antiviral genes.
AB  - Innate immunity is the first line against the invasion of pathogenic
      microorganisms. Previous reports only demonstrated production traits of
      commercial importance were often negatively correlated with innate disease
      resistance. However, whether different purpose of artificial selection influences
      innate immunity have not been understood. In this study, we cloned exon1, exon6
      of IFIH1 and exon2 of IFIT5 by molecular biology techniques in seven different
      chicken breeds to detect the potential effect of artificial selection for
      commercial traits on disease resistance for the first time. In total, 8 single
      nucleotide polymorphisms(SNPs) of IFIH1 gene exon1 and exon6, 19 SNPs of IFIT5
      gene exon2 were detected. We found all native chicken breeds had a relatively
      close relationship to broiler breeds but a remote relationship to layer breed. A
      great difference between CB and LLH with different selected purpose were
      observed. The allele frequencies of these two positive antiviral genes were
      associated with different purpose of artificial selection. Our experiment
      constituted the foundation for the interaction between commercial traits and
      immune trait.

PMID- 29066168
TI  - Patterns and predictors of physician adoption of new cardiovascular drugs.
AB  - BACKGROUND: Little is known about physicians' approaches to adopting new
      cardiovascular drugs and how adoption varies between drugs of differing novelty.
      METHODS: Using data on dispensed prescriptions from IMS Health's XponentTM
      database, we created a cohort of all primary care physicians (PCPs) and
      cardiologists in Pennsylvania who regularly prescribed anticoagulants,
      antihypertensives and statins from 2007 to 2011. We examined prescribing of three
      new cardiovascular drugs of differing novelty: dabigatran, aliskiren and
      pitavastatin. Outcomes were rapid adoption of each new drug, defined by early and
      sustained monthly prescribing detected by group-based trajectory models, by
      physicians within the first 15 months of marketplace introduction. RESULTS: 5953
      physicians regularly prescribed each drug class. The majority of physicians
      (63.8%) adopted zero new drugs in the first 15 months, 35.0% rapidly adopted one
      or two, and 1.2% rapidly adopted all three. Physicians were more likely to
      rapidly adopt the most novel drug, dabigatran (27.3%), than aliskiren (10.5%) or
      pitavastatin (8.0%). Physician specialty and sex were the most consistent
      predictors of adoption. Compared to PCPs, cardiologists were more likely to
      rapidly adopt dabigatran (Adjusted Odds Ratio 8.90, 95% confidence interval 7.42
      10.67; P<0.001) aliskerin (2.05, CI 1.56-2.69; P<0.001) and pitavastatin (3.44,
      CI 2.60-4.57; P<0.001). Female physicians were less likely to adopt dabigatran
      (0.71, CI 0.59-0.85; P <0.001) and aliskiren (0.64, CI 0.49-0.83; P <0.001).
      CONCLUSIONS: Physicians vary in their prescribing of recently-introduced
      cardiovascular drugs. Though most physicians did not rapidly adopt any new
      cardiovascular drugs, drug novelty and cardiology training were associated with
      greater adoption.

PMID- 29066171
TI  - Modern Challenges of Cancer Clinical Trials.

PMID- 29066170
TI  - Codon usage pattern of complex III gene of respiratory chain among
      platyhelminths.
AB  - Codon usage bias refers to the phenomenon where synonymous codons are used with
      unequal frequencies. To understand the patterns of codon usage in mitochondrial
      cytochrome B (MT-CYB) gene of phylum platyhelminthes we used bioinformatic
      approaches to analyze the protein coding sequences of five different classes -
      cestoda, monogenea, rabditophora, trematoda and turbellaria. It was found from
      nucleotide composition analysis that in all the classes, A/T-ended codons were
      preferred to G/C -ended codons. From box plot analysis GC1 was found to have
      highest response to codon usage bias. Correspondence analysis indicated that
      besides mutation other factors such as natural selection might also affect the
      codon usage pattern. Neutrality plot reveals that both mutation and natural
      selection played role in codon usage pattern in five classes of MT-CYB gene.
      Various factors namely nucleotide composition, natural selection and mutation
      pressure affected the codon usage pattern.

PMID- 29066172
TI  - Effects of nanosized titanium dioxide on the photosynthetic metabolism of
      fenugreek (Trigonella foenum-graecum L.).
AB  - The potential toxicity of nanoparticles in plants is scarce and contradictory.
      Despite the diversity of research efforts, a detailed explanation of the TiO2NPS
      effects in plant photosynthesis is still missing. The present work gives a new
      approach to examine the impact of the TiO2NPs on crop production (development and
      photosynthesis) and plant protection (tolerance and defense systems) in fenugreek
      (Trigonella foenum graecum L.). Seedlings were assessed in greenhouse trials to
      estimate the influence of TiO2NPs on physiological characters for 16 days. They
      were treated with TiO2NPs at a size less than 20nm. The results revealed that
      there were no significant effects on seedlings growth and biomass of stem, but a
      decrease in the fresh weight of leaves after TiO2NPs treatment. Plants treated
      with 100mg.L-1 of TiO2NPs presented a reduction and chlorosis in leaf area due to
      a significant decrease in the chlorophyll a and b contents. The highest value of
      the photosynthetic pigments was recorded at 50mg.L-1 of TiO2NPs. However, the
      treatment with 100mg.L-1 of TiO2NPs caused a decrease in the levels of
      chlorophyll a, b and of carotenoids. Both doses of TiO2NPs induced an
      accumulation of anthocyanins compared to the control after 16 days of seedling
      development. A nano-stress significantly decreased the flavonoids level, but
      increased that of polyphenols compared to control after 16 days of exposure. The
      decrease in the translocation ratio of flavonoids suggests that many of them
      contain an enediol group, which suggests that they may act as bidentate ligands
      for anatase TiO2NPs. Accordingly, nano-stressed leaves exhibited significantly
      enhanced GPOX, CAT and APX activity levels. On the contrary, GPOX and CAT
      activities were reduced substantially in stems treated with 100mg.L-1 TiO2NPs.
      The accumulation of MDA was found to be higher in stems than in leaves. This
      could be explained by the accumulation of nanoparticles in different organs; it
      could be that the stems are the favored targets of nanoparticles. These results
      underline the necessity for a deeper estimation of nanoparticle ecotoxicity and
      particularly concerning their interaction with plants.

PMID- 29066173
TI  - Anemia in patient with primary hyperoxaluria and bone marrow involvement by
      oxalate crystals.
AB  - We present a rare case of anaemia secondary to bone marrow infiltration by
      oxalate crystals and renal failure in a patient diagnosed with primary
      hyperoxaluria. In our case, the anaemia was recovered after the double liver and
      kidney transplantation, the latter was performed on two occasions after the
      failure of the first graft.

PMID- 29066175
TI  - Effects of yogic exercise on nonspecific neck pain in university students.
AB  - OBJECTIVE: To assess the effects of yogic exercise on nonspecific neck pain in
      university students. METHODS: This study is a pretest-posttest design with a non
      equivalent control group. Thirty-eight university students were selected by
      convenience sampling, with 18 assigned to an exercise group and 20 assigned to a
      control group. The yoga group participated in one-hour sessions of yogic exercise
      two days a week for eight weeks. The exercise comprised eight stages: relaxation,
      flexion of neck, extension of neck, right lateral flexion of neck, left lateral
      flexion of neck, right rotation of neck, left rotation of neck, and relaxation.
      Neck pain intensity was measured using a 100 mm visual analogue scale. RESULTS:
      The yoga group showed significantly decreased neck pain scores compared with
      those of the control group. CONCLUSIONS: These findings indicate that yogic
      exercises could reduce neck pain in university students.

PMID- 29066177
TI  - Barriers and Strategies for Healthy Food Choices among American Indian Tribal
      College Students: A Qualitative Analysis.
AB  - BACKGROUND: American Indian and Alaskan Native individuals experience
      disproportionate levels of chronic health conditions such as type 2 diabetes and
      overweight and obesity that are influenced by dietary patterns and food choices.
      Understanding factors that influence healthy food choices among tribal college
      students can enrich education and programs that target dietary intake. OBJECTIVE:
      To build an understanding of factors that influence healthy food choices among
      tribal college students at increased risk for college attrition. DESIGN: A
      nonexperimental cohort design was used for qualitative descriptive analysis.
      PARTICIPANTS/SETTING: Participants (N=20) were purposively sampled, newly
      enrolled, academically underprepared tribal college students enrolled in a
      culturally relevant life skills course at an upper Midwest tribal college between
      September 2013 and May 2015. Participant demographic characteristics included
      various tribal affiliations, ages, and number of dependents. MAIN OUTCOME
      MEASURES: Participant responses to qualitative research questions about dietary
      intake, food choices, self-efficacy for healthy food choices, psychosocial
      determinants, and barriers to healthy food choices during telephone interviews
      were used as measures. ANALYSIS: Qualitative analysis included prestudy
      identification of researcher bias/assumptions, audiorecording and transcription,
      initial analysis (coding), secondary analysis (sorting and identifying meaning),
      and verification (comparative pattern analysis). RESULTS: Qualitative analysis
      revealed a variety of themes and subthemes about healthy food choices. Main
      themes related to barriers included taste, food gathering and preparation, and
      difficulty clarifying healthy food choices. Main themes related to strategies
      included taste, cultural traditions and practices, and personal motivation
      factors. CONCLUSIONS: Qualitative analysis identified barrier and strategy themes
      that may assist nutrition and dietetics practitioners working with
      tribal/indigenous communities, tribal college educators and health specialists,
      and tribal community health workers who target health and dietary intake of
      American Indian and Alaskan Native students.

PMID- 29066174
TI  - Attenuation of CD4+CD25+ Regulatory T Cells in the Tumor Microenvironment by
      Metformin, a Type 2 Diabetes Drug.
AB  - CD4+CD25+ regulatory T cells (Treg), an essential subset for preventing
      autoimmune diseases, is implicated as a negative regulator in anti-tumor
      immunity. We found that metformin (Met) reduced tumor-infiltrating Treg (Ti
      Treg), particularly the terminally-differentiated CD103+KLRG1+ population, and
      also decreased effector molecules such as CTLA4 and IL-10. Met inhibits the
      differentiation of naive CD4+ T cells into inducible Treg (iTreg) by reducing
      forkhead box P3 (Foxp3) protein, caused by mTORC1 activation that was determined
      by the elevation of phosphorylated S6 (pS6), a downstream molecule of mTORC1.
      Rapamycin and compound C, an inhibitor of AMP-activated protein kinase (AMPK)
      restored the iTreg generation, further indicating the involvement of mTORC1 and
      AMPK. The metabolic profile of iTreg, increased Glut1-expression, and reduced
      mitochondrial membrane-potential and ROS production of Ti-Treg aided in
      identifying enhanced glycolysis upon Met-treatment. The negative impact of Met on
      Ti-Treg may help generation of the sustained antitumor immunity.

PMID- 29066176
TI  - Maternal cardiac function in gestational hypertension, mild and severe
      preeclampsia and normal pregnancy: A comparative study.

PMID- 29066178
TI  - Tumor angiogenesis and bone metastasis - Correlation in invasive breast
      carcinoma.
AB  - PURPOSE: To test the hypotheses that pathological biomarkers including CD34
      positive endothelial cell and microvessel density (MVD) of the primary breast
      tumor can be used to predict the probability of occurrence for bone metastases
      and provide information for appropriate therapeutic strategies at an early stage.
      METHODS: Three groups of CD34 immunohistochemical stained slices (n=60) were
      acquired from surgical specimens of sixty patients including non-metastasis
      (group 1), only lymph node metastasis (group 2), and bone metastasis (group 3).
      MVD was measured by TissueGnostics system. RESULTS: The MVD measurement results
      were 57.14+/-23.00 in group 1, 86.44+/-21.13 in group 2, and 126.85+/-47.89 in
      group 3. There were statistical differences between group 1 and group 2
      (P=0.0002), between group 2 and group 3 (P=0.0014) and between group 1 and group
      3 (P<0.0001). The strong correlations were found between CD34 positive cell
      measurement and its percentage (group 1, r=0.74, P=0.0002; group 2, r=0.62,
      P=0.0034; group 3, r=0.84, P<0.0001), and between CD34 positive endothelial cell
      measurement and MVD (r=0.61, P<0.0001). CONCLUSIONS: Quantitative CD34 positive
      endothelial cell and MVD measurements of the primary breast tumor have a strong
      correlation with the occurrence rate of bone metastases, which predicts the
      probability of occurrence for bone metastases at an early stage.

PMID- 29066179
TI  - Ethical implications of the use of decision aids for antenatal counseling at the
      limits of gestational viability.
AB  - Shared decision-making is a recent priority in neonatology. However, its
      implementation is at an early stage. Decision aids are tools designed to assist
      in shared decision-making. They help patients competently participate in making
      healthcare decisions. There are limited studies in neonatology on the formal use
      of decision aids as used in adult medicine. Decision aids are relatively new,
      even in adult medicine where they were pioneered; therefore, there is a lack of
      systematic oversight to their development and use. Despite evidence reporting a
      powerful effect on patients' decisions, decision aids are not subject to quality
      control, leading to potentially enormous ethical implications. These include: (i)
      possible introduction of developers' biases; (ii) use of outdated or incorrect
      information; (iii) misuse to steer a patient towards less expensive treatments;
      (iv) clinician liability if negative patient outcomes occur, since decision aids
      are currently not standard of care.

PMID- 29066180
TI  - Preliminary pharmacokinetics of tramadol hydrochloride after administration via
      different routes in male and female B6 mice.
AB  - OBJECTIVE: 1) To determine the pharmacokinetics of tramadol hydrochloride and its
      active metabolite, O-desmethyltramadol (M1), after administration through
      different routes in female and male C57Bl/6 mice; 2) to evaluate the stability of
      tramadol solutions; and 3) to identify a suitable dose regimen for prospective
      clinical analgesia in B6 mice. STUDY DESIGN: Prospective, randomized, blinded,
      parallel design. ANIMALS: A total of 18 male and 18 female C57Bl/6 mice (20-30
      g). METHODS: Mice were administered 25 mg kg-1 tramadol as a bolus [intravenously
      (IV), intraperitoneally (IP), subcutaneously (SQ), orally per gavage (OSgavage)]
      over 25 hours [orally in drinking water (OSwater) or Syrspend SF (OSSyrsp)].
      Venous blood was sampled at six predetermined time points over 4 to 31 hours,
      depending on administration route, to determine tramadol and M1 plasma
      concentrations (liquid chromatography and tandem mass spectrometry detection).
      Pharmacokinetic parameters were described using a noncompartmental model. The
      stability of tramadol in water (acidified and untreated) and Syrspend SF (0.20 mg
      mL-1) at ambient conditions for 1 week was evaluated. RESULTS: After all
      administration routes, Cmax was >100 ng mL-1 for tramadol and >40 ng mL-1 for M1
      (reported analgesic ranges in man) followed by short half-lives (2-6 hours). The
      mean tramadol plasma concentration after self-administration remained >100 ng mL
      1 throughout consumption time. M1 was found in the OSSyrs group only at 7 hours,
      whereas it was detectable in OSwater throughout administration. Tramadol had low
      oral bioavailability (26%). Short-lasting side effects were observed only after
      IV administration. Water and Syrspend SF solutions were stable for 1 week.
      CONCLUSIONS AND CLINICAL RELEVANCE: 1) At the dose administered, high plasma
      concentrations of tramadol and M1 were obtained, with half-life depending on the
      administration route. 2) Plasma levels were stable over self-consumption time. 3)
      Solutions were stable for 1 week at ambient conditions.

PMID- 29066182
TI  - Tetramethylpyrazine suppresses angiotensin II-induced soluble epoxide hydrolase
      expression in coronary endothelium via anti-ER stress mechanism.
AB  - Activation of soluble epoxide hydrolase (sEH) is associated with endothelial
      dysfunction in hypertension, though the underlying mechanisms are inadequately
      understood and the role of endoplasmic reticulum (ER) stress is yet to be studied
      in detail. Tetramethylpyrazine (TMP), a major bioactive ingredient of Chinese
      herb Chuanxiong, is well-known for its cardiovascular benefits. Nevertheless,
      whether TMP may protect vascular endothelium from ER stress and whether
      regulation of sEH is involved remain unknown. This study aimed at investigating
      the role of ER stress in angiotensin-II (Ang-II)-induced sEH dysregulation and
      elucidating the significance of ER stress regulation in the vasoprotective effect
      of TMP. Porcine primary coronary artery endothelial cells (PCECs) were used for
      western blot, ELISA, and reverse-transcription PCR analysis. Porcine coronary
      arteries were assessed in a myograph for endothelial dilator function. Ang-II
      induced expression of ER stress molecules in PCECs meanwhile enhanced sEH
      expression and decreased 11,12-EET. Exposure of PCECs to the chemical ER stress
      inducer tunicamycin also increased sEH expression. Inhibition of ER stress
      suppressed sEH upregulation, resulting in an increase of 11,12-EET. The
      impairment of endothelium-dependent vasorelaxation induced by Ang-II or
      tunicamycin was ameliorated by inhibitors of ER stress or sEH. TMP showed
      comparable inhibitory effect to ER stress inhibitors on the expression of ER
      stress molecules, the dysregulation of sEH/EET, and the impairment of endothelial
      dilator function. We demonstrated that ER stress mediates Ang-II-induced sEH
      upregulation in coronary endothelium. TMP has potent anti-ER stress capacity
      through which TMP normalizes sEH expression and confers protective effect against
      Ang-II on endothelial function of coronary arteries.

PMID- 29066181
TI  - Dafachronic acid inhibits C. elegans germ cell proliferation in a DAF-12
      dependent manner.
AB  - Dafachronic acid (DA) is a bile acid-like steroid hormone that regulates dauer
      formation, heterochrony, and lifespan in C. elegans. Here, we describe that DA is
      an inhibitor of C. elegans germ stem cell proliferation in adult hermaphrodites.
      Using a C. elegans germ cell primary culture system, we show that DA inhibits the
      proliferation of germ cells in vitro. Exogenous DA reduces the frequency of large
      tumors in adult tumorous germline mutants and decreases the proliferation of wild
      type germ stem cells in adult hermaphrodites. In contrast, DA has no appreciable
      effect on the proliferation of larval-stage germ cells in wild type. The
      inhibition of adult germ cell proliferation by DA requires its canonical receptor
      DAF-12. Blocking DA production by inactivating the cytochrome P450 DAF-9
      increases germ cell proliferation in wild-type adult hermaphrodites and the
      frequency of large tumors in germline tumorous mutants, suggesting that DA
      inhibits the rate of germ cell proliferation under normal growth conditions.

PMID- 29066183
TI  - A genetic mutation panel for differentiating malignant phyllodes tumour from
      metaplastic breast carcinoma.

PMID- 29066184
TI  - Unusual cause of hoarseness: Arytenoid cartilage dislocation without a traumatic
      event.
AB  - Arytenoid cartilage dislocation is a rare but curable cause of hoarseness and is
      commonly related to intubation or laryngeal trauma. We present a case of
      arytenoid cartilage dislocation without a traumatic event in a man who complained
      of acute hoarseness. An 82-year-old man visited our emergency department
      complaining of acute hoarseness. He had no history of general anesthesia or
      laryngeal trauma and had not caught a cold. He showed no abnormal physical
      findings including the pharynx. Examination using a laryngoscope revealed that
      the left vocal fold was fixed in the paramedian position. We performed contrast
      enhanced computed tomography (CT), but we could not find any cause of the left
      recurrent laryngeal nerve paralysis. His hoarseness persisted for one month and
      the initial CT was therefore reassessed. It was found that the left arytenoid
      cartilage was dislocated forward, and we therefore made a diagnosis of arytenoid
      cartilage dislocation without a traumatic event. We tried to refer him to an
      otolaryngologist for surgical treatment, but he declined. Fortunately, his
      hoarseness gradually improved over a period of two months. Arytenoid cartilage
      dislocation rarely occurs without a traumatic event. CT is useful for accurate
      diagnosis of this condition. Since early diagnosis can lead to appropriate
      surgical treatment and improvement in vocal function, the possibility of
      arytenoid cartilage dislocation should be considered in patients with acute
      hoarseness without apparent causes.

PMID- 29066185
TI  - Effect of simulation-based sedation training course for dentists on emergency
      response monitoring.

PMID- 29066186
TI  - A method combining cricoid pressure and manual laryngeal fixation during chest
      compression to facilitate emergency tracheal intubation.

PMID- 29066163
TI  - Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody
      positive refractory generalised myasthenia gravis (REGAIN): a phase 3,
      randomised, double-blind, placebo-controlled, multicentre study.
AB  - BACKGROUND: Complement is likely to have a role in refractory generalised
      myasthenia gravis, but no approved therapies specifically target this system.
      Results from a phase 2 study suggested that eculizumab, a terminal complement
      inhibitor, produced clinically meaningful improvements in patients with anti
      acetylcholine receptor antibody-positive refractory generalised myasthenia
      gravis. We further assessed the efficacy and safety of eculizumab in this patient
      population in a phase 3 trial. METHODS: We did a phase 3, randomised, double
      blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and
      specialised clinics in 17 countries across North America, Latin America, Europe,
      and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis
      Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis
      Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria
      meningitides, and previous treatment with at least two immunosuppressive
      therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin
      or plasma exchange for 12 months without symptom control. Patients with a history
      of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or
      use of intravenous immunoglobulin or plasma exchange within 4 weeks before
      randomisation, or rituximab within 6 months before screening, were excluded. We
      randomly assigned participants (1:1) to either intravenous eculizumab or
      intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day
      1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second
      week thereafter as maintenance dosing. Randomisation was done centrally with an
      interactive voice or web-response system with patients stratified to one of four
      groups based on MGFA disease classification. Where possible, patients were
      maintained on existing myasthenia gravis therapies and rescue medication was
      allowed at the study physician's discretion. Patients, investigators, staff, and
      outcome assessors were masked to treatment assignment. The primary efficacy
      endpoint was the change from baseline to week 26 in MG-ADL total score measured
      by worst-rank ANCOVA. The efficacy population set was defined as all patients
      randomly assigned to treatment groups who received at least one dose of study
      drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG
      ADL assessment. The safety analyses included all randomly assigned patients who
      received eculizumab or placebo. This trial is registered with ClinicalTrials.gov,
      number NCT01997229. FINDINGS: Between April 30, 2014, and Feb 19, 2016, we
      randomly assigned and treated 125 patients, 62 with eculizumab and 63 with
      placebo. The primary analysis showed no significant difference between eculizumab
      and placebo (least-squares mean rank 56.6 [SEM 4.5] vs 68.3 [4.5]; rank-based
      treatment difference -11.7, 95% CI -24.3 to 0.96; p=0.0698). No deaths or cases
      of meningococcal infection occurred during the study. The most common adverse
      events in both groups were headache and upper respiratory tract infection (ten
      [16%] for both events in the eculizumab group and 12 [19%] for both in the
      placebo group). Myasthenia gravis exacerbations were reported by six (10%)
      patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%)
      patients in the eculizumab group and 12 (19%) in the placebo group required
      rescue therapy. INTERPRETATION: The change in the MG-ADL score was not
      statistically significant between eculizumab and placebo, as measured by the
      worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank
      analytical approach proved to be an important limitation of this study since the
      secondary and sensitivity analyses results were inconsistent with the primary
      endpoint result; further research into the role of complement is needed. FUNDING:
      Alexion Pharmaceuticals.

PMID- 29066187
TI  - Primary Adrenal Failure in the Emergency Department.
AB  - BACKGROUND: Primary adrenal failure is considered to be an extremely rare disease
      presenting in the ED, with an incidence reported to be as low as 50 cases per
      1,000,000 persons (Klauer, 2017). I would like to present a case of a young man
      who presented to the ED, with what I suspected to be this rare entity. CASE
      REPORT: A 26year old otherwise healthy male presented to our ED with complaints
      of weakness, nausea, vomiting, and hiccups of 1.5-day duration. He also
      complained of lightheadedness, describing it as if he was going to pass out.
      Other than slight tachycardia (100) and darkened skin, his physical exam, ROS,
      PMH, Family and Social History, were all unremarkable. His sodium returned at
      111, and he was later noted to become more confused in the ED prompting the
      emergent use of Hypertonic Saline. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: Albeit a rare disease entity, EPs need to keep this life threatening
      disease process in the back of their minds when presented with a patient with
      vague symptoms such as weakness or fatigue, electrolyte abnormalities and
      darkening of their skin.

PMID- 29066188
TI  - Early hemoperfusion for emergency treatment of carbamazepine poisoning.
AB  - OBJECTIVES: To investigate the clinical value of early hemoperfusion (HP) in
      emergency treatment of carbamazepine (CBZ) poisoning. METHODS: 104 patients with
      acute CBZ poisoning treated from August 2004 to October 2015 in the Emergency
      Department were reviewed. Patients were categorized into three groups: group A,
      who received HP treatment in the Emergency Department; group B, who received HP
      treatment in the blood purification room; and group C, who did not received HP
      treatment. Pharmacokinetic parameters of CBZ and remission of complications were
      compared among the three groups. RESULTS: Both groups A and B had lower time to
      peak, area under curve and maximum concentration values than group C (P<0.05),
      and these kinetics indexes were significantly lower in group A than in group B
      (P<0.05). The mean retention times were 0.85+/-0.08, 1.20+/-0.15 and 2.52+/
      0.29days in the three groups, respectively, and were significantly lower value in
      group A than in group B (P<0.05). The incidences of respiratory depression and
      seizure in group A were significantly lower than those of groups B and C
      (P<0.05). Group A had significantly higher Glasgow coma scale (GCS) scores at 4h
      after admission than the other two groups (P<0.05), and group B had significantly
      higher GCS scores than group C at 6h after admission (P<0.05). CONCLUSIONS:
      Initiation of HP in the early treatment stage of CBZ poisoning upon admission to
      an emergency department can significantly reduce the plasma concentration and
      retention period of CBZ, relieve the symptoms and shorten the overall treatment
      period.

PMID- 29066189
TI  - Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator
      knowledge, attitudes and practices.
AB  - INTRODUCTION: The introduction of new vaccines highlights concerns about high
      vaccine wastage, knowledge of wastage policies and quality of stock management.
      However, an emphasis on minimizing wastage rates may cause confusion when
      recommendations are also being made to reduce missed opportunities to routinely
      vaccinate children. This concern is most relevant for lyophilized vaccines
      without preservatives [e.g. measles-containing vaccine (MCV)], which can be used
      for a limited time once reconstituted. METHODS: We sampled 54 health facilities
      within 11 local government areas (LGAs) in Nigeria and surveyed health sector
      personnel regarding routine vaccine usage and wastage-related knowledge and
      practices, conducted facility exit interviews with caregivers of children about
      missed opportunities for routine vaccination, and abstracted vaccine stock
      records and vaccination session data over a 6-month period to calculate wastage
      rates and vaccine vial usage patterns. RESULTS: Nearly half of facilities had
      incomplete vaccine stock data for calculating wastage rates. Among facilities
      with sufficient data, mean monthly facility-level wastage rates were between 18
      and 35% across all reviewed vaccines, with little difference between lyophilized
      and liquid vaccines. Most (98%) vaccinators believed high wastage led to recent
      vaccine stockouts, yet only 55% were familiar with the multi-dose vial policy for
      minimizing wastage. On average, vaccinators reported that a minimum of six
      children must be present prior to opening a 10-dose MCV vial. Third dose of
      diphtheria-tetanus-pertussis vaccine (DTP3) was administered in 84% of sessions
      and MCV in 63%; however, the number of MCV and DTP3 doses administered were
      similar indicating the number of children vaccinated with DTP3 and MCV were
      similar despite less frequent MCV vaccination opportunities. Among caregivers,
      30% reported being turned away for vaccination at least once; 53% of these
      children had not yet received the missed dose. DISCUSSION: Our findings show
      inadequate implementation of vaccine management guidelines, missed opportunities
      to vaccinate, and lyophilized vaccine wastage rates below expected rates. Missed
      opportunities for vaccination may occur due to how the health system's
      contradicting policies may force health workers to prioritize reduced wastage
      rates over vaccine administration, particularly for multi-dose vials.

PMID- 29066190
TI  - Identification of new shikonin derivatives as STAT3 inhibitors.
AB  - The signal transducer and activator of transcription 3 is a constitutively
      activated oncogenic protein in various human tumors and represents a valid target
      for anticancer drug design. In this study, we have achieved a new type of STAT3
      inhibitors based on structural modifications on shikonin scaffold, guided by
      computational modelling. By tests, PMMB-187 exhibited a more outstanding profile
      than shikonin on a small panel of human breast cancer cells, especially for the
      MDA-MB-231 cells. For the cellular mechanisms research, PMMB-187 was found to
      induce cell apoptosis in MDA-MB-231 cells, associated with the reduction of
      mitochondrial membrane potential, production of ROS and alteration of the levels
      of apoptosis-related proteins. Furthermore, PMMB-187 inhibited
      constitutive/inducible STAT3 activation, transcriptional activity, nuclear
      translocation and downstream target genes expression in STAT3-dependent breast
      cancer cells MDA-MB-231. Besides, no obvious inhibitory effect on activation of
      STAT1 and STAT5 was observed with PMMB-187 treatment. Most notably, the in vivo
      studies further revealed that PMMB-187 could dramatically suppress the MDA-MB-231
      cells xenografted tumor growth. The in vitro and in vivo results collectively
      suggest that PMMB-187 may serve as a promising lead compound for the further
      development of potential therapeutic anti-neoplastic agents.

PMID- 29066191
TI  - Low gait efficiency is the primary reason for the increased metabolic demand
      during gait in children with cerebral palsy.
AB  - Children diagnosed with cerebral palsy (CP) use two to three times more metabolic
      energy to walk than their typically developing (TD) peers. The primary cause of
      the metabolic increase remains unknown. In this study, we analyzed metabolic
      energy, center of mass (COM) work, and gait efficiency for a large group of
      children diagnosed with diplegic CP in order to better understand the source of
      the excessive metabolic demand. Our primary hypothesis is that metabolic demand
      is increased in CP due to low efficiency conversion of metabolic energy into
      useful COM work. Results show that, on average, individuals with CP produce 27%
      more COM work, but have 99% higher metabolic demand than their TD peers. This
      causes individuals with CP to have a gait efficiency that is 31% lower than the
      gait efficiency of TD individuals. Therefore, low efficiency is responsible for
      nearly three quarters of the increase in metabolic demand. These results show
      that the high metabolic demands in CP are largely a result of low gait
      efficiency, not excessive COM work. Further work is needed to identify the
      specific neurological and biomechanical mechanisms underlying low gait efficiency
      in CP.

PMID- 29066192
TI  - Observations of tropospheric aerosols and NO2 in Hong Kong over 5years using
      ground based MAX-DOAS.
AB  - In this paper, we present long term observations of atmospheric aerosols and
      nitrogen dioxide (NO2) in Hong Kong using a Multi-AXis Differential Optical
      Absorption Spectroscopy (MAX-DOAS) instrument. Ground based MAX-DOAS measurements
      were performed over 5years from December 2010 to November 2015. Vertical
      distribution profiles of aerosols and NO2 were derived from MAX-DOAS O4 and NO2
      observations by applying the optimal estimation method. Retrieved MAX-DOAS
      measurements of aerosols and NO2 show good agreement with sun photometer
      observation of aerosol optical depths (AODs) and long path DOAS measurement of
      ground level NO2 mixing ratios. Tropospheric vertical column densities (VCDs) of
      NO2 derived from MAX-DOAS measurements are used to validate OMI satellite NO2
      observations. Daily data show reasonably good agreement with each other with
      Pearson correlation coefficient R=0.7. However, MAX-DOAS NO2 VCDs are on average
      higher than OMI observations by a factor of 2. Introducing aerosols in the air
      mass factor calculation would enhance the OMI VCDs by 7-13%, the remaining
      discrepancy is mainly due to the differences in spatial coverage between the two
      instruments. Diurnal variation patterns of aerosols and NO2 indicated significant
      contributions from local anthropogenic emissions. Analysis of air mass transport
      shows that the enhancement of surface aerosols and NO2 concentrations mainly
      results from accumulation of local emissions under low wind speed conditions.

PMID- 29066193
TI  - Temporal trends of PBDD/Fs, PCDD/Fs, PBDEs and PCBs in ringed seals from the
      Baltic Sea (Pusa hispida botnica) between 1974 and 2015.
AB  - Temporal trends in exposure to persistent organic pollutants (POPs) were assessed
      in 22 pooled samples gathered from 69 individuals of Baltic ringed seal (Pusa
      hispida botnica) from 1974 to 2015. Samples were analysed for polybrominated
      dibenzo-p-dioxins and furans (PBDD/Fs), polychlorinated dibenzo-p-dioxins and
      furans (PCDD/Fs), polybrominated diphenyl ethers (PBDEs) and polychlorinated
      biphenyls (PCBs). No previous study has reported on the occurrence of PBDD/Fs in
      marine mammals in the Baltic Sea. Concentrations of pollutants in Baltic ringed
      seal, a marine mammal and top predator, can be used as an indicator of pollutants
      concentrations in the Baltic region. Visual inspection of data did not show any
      temporal trends for PBDD/Fs, while the PCDD/Fs and PCBs showed decreasing
      concentrations between 1974 and 2015. PBDEs increased until the end of the 1990s
      and then decreased until the end of the period. ?PBDD/Fs ranged from 0.5-52.3pg/g
      lipid weight (l.w.) (0.08-4.8pgTEQ/g l.w.), with 1,2,3,4,6,7,8-HpBDF contributing
      on average 61% to ?PBDD/Fs. ?PCDD/Fs ranged from 103 to 1480pg/g l.w. (39
      784pgTEQ/g l.w.), with 1,2,3,6,7,8-HxCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF
      showing the highest average concentrations. PBDD/F toxic equivalents (TEQ)
      contributed on average 1.1% to the total (PBDD/F+PCDD/F) TEQ. The ?PBDEs
      concentration range was 18.7-503ng/g l.w., with BDE #47 the predominant congener.
      The concentration range for ?PCBs was 2.8-40.1MUg/g l.w., with #138 and #153 the
      most abundant congeners. Visual inspection of the data showed decreasing
      concentrations for all compound groups except PBDD/Fs. A slight increase in the
      PBDD/Fs concentrations was observed from 2004 onwards. This observation needs to
      be investigated further.

PMID- 29066194
TI  - Plasma concentration of 14 perfluoroalkyl acids (PFAAs) among children from seven
      cities in Guangdong, China.
AB  - The toxicity and persistence of perfluoroalkyl acids (PFAAs) in humans have drawn
      growing concerns, particularly for children. However, data regarding the
      concentrations of PFAAs in children are limited. In this study, we measured the
      concentrations of 14 PFAAs in plasma samples collected from 1192 children aged 0
      7years from 7 cities in Guangdong Province: Guangzhou, Shenzhen, Foshan,
      Dongguan, Zhaoqing, Zhongshan and Zhanjiang. Perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA) were detected in >99.5% of the analysed samples.
      PFOS had the highest median concentration (23.6ng/mL) in the total samples,
      followed by PFOA (2.8ng/mL). The median concentrations of the other PFAAs were
      lower than 0.4ng/mL. The concentrations of perfluorohexanoic acid,
      perfluorononanoic acid, perfluorodecanoic acid, perfluorododecanoic acid,
      perfluorohexane sulfonate, PFOA and PFOS in children from Foshan were
      significantly higher than those found in other cities (p<0.001). Negative
      correlations between most of the PFAA concentrations and age (r=-0.06--0.45) were
      found in all children. Weak to moderate correlations (r=0.080-0.698) were
      observed between all PFAA concentrations. Our findings indicated a high exposure
      of children to PFAAs in the early life-stage. The exposure sources and pathways
      of PFAAs in different regions are different. Considering a lack of information on
      the exposure pathways and health status, more studies are needed to evaluate the
      exposure resources and assess the health risk of PFAA exposure in children.

PMID- 29066195
TI  - Supplemental feeding and other anthropogenic threats to green turtles (Chelonia
      mydas) in the Canary Islands.
AB  - Green turtles are found in the waters of the Canary Islands but little is known
      about the ecology and anthropogenic pressures that threaten them. Our results
      have revealed that juvenile green turtles, ranging in curve carapace length from
      26.9-81.0cm, are regularly found in the archipelago and originate from rookeries
      in both the eastern and western Atlantic. Photo-identification and satellite
      tracking showed high levels of site fidelity to coastal foraging grounds
      associated with seagrass meadows, but stable isotope analysis indicated animal
      based omnivorous diets after settlement on the continental shelf, with no
      increase in the consumption of macrophytes as the turtles grew. Most turtles
      exhibited high levels of some blood biochemical markers associated with a high
      consumption of proteins and fat. In addition, we determined levels of some
      organic and inorganic pollutants. Supplemental feeding may also contribute to
      explain the high prevalence of hooking and boat strikes in the green turtles
      brought to wildlife rescue centers as compared with loggerhead turtles.
      Regulatory measures and surveillance should be urgently implemented in order to
      improve the status of the species in the archipelago.

PMID- 29066196
TI  - Erodibility of waste (Loess) soils from construction sites under water and wind
      erosional forces.
AB  - Excess soils from construction sites (waste soils) become a problem when exposed
      to soil erosion by water or wind. Understanding waste soil erodibility can
      contribute to its proper reuse for various surface applications. The general
      objective of the study was to provide a better understanding of the effects of
      soil properties on erodibility of waste soils excavated from various depths in a
      semiarid region under rainfall and wind erosive forces. Soil samples excavated
      from the topsoil (0-0.3m) and subsoil layers (0.3-0.9 and >1m depths) were
      subjected to simulated rainfall and wind. Under rainfall erosive forces, the
      subsoils were more erodible than the topsoil, in contrast to the results obtained
      under wind erosive forces. Exchangeable sodium percentage was the main factor
      controlling soil erodibility (Ki) under rainfall, and a significant logarithmic
      regression line was found between these two parameters. In addition, a
      significant, linear regression was found between Ki and slaking values for the
      studied soil samples, suggesting that the former can be predicted from the
      latter. Soil erodibility under wind erosion force was controlled mainly by the
      dry aggregate characteristics (mean weight diameter and aggregate density): their
      higher values in the subsoil layers resulted in lower soil erodibility compared
      to the topsoil.

PMID- 29066197
TI  - Riverine phytoplankton shifting along a lentic-lotic continuum under
      hydrological, physiochemical conditions and species dispersal.
AB  - The importance of phytoplankton-based bio-assessment has been recently recognized
      in lowland rivers which are affected by multi-environmental factors. However,
      some basic questions remain unclear to date, such as: (i) spatial and temporal
      variations of phytoplankton, (ii) the impact of upstream lakes on downstream
      community, (iii) the main drivers for species composition or (iv) the regional
      biodiversity along a lentic-lotic continuum. To answer these questions, we
      collected and analyzed the fluvial phytoplankton communities along a lentic-lotic
      continuum from a German lowland catchment, where a well-established
      ecohydrological modeling predicted long-term discharges at each sampling site.
      Our results revealed very high spatial and temporal variations of phytoplankton
      community. The changes of a lake on downstream phytoplankton assemblages were
      significant, especially the nearest reach after the lake. However, these
      influences varied along with seasons and limited in a relatively short distance
      to the lake. Redundancy analysis and Mantel tests showed that phytoplankton
      composition and dissimilarities along the lentic-lotic continuum attributed more
      to local hydrological and physicochemical variables than species dispersal, which
      confirmed the suitability of lowland phytoplankton-based bioassessment. In
      addition, our findings highlighted the importance of flow regime in shaping
      phytoplankton community composition and regional beta diversities. This study
      emphasized the necessity to include the hydrological variables and their
      relationship with phytoplankton community in future bio-monitoring
      investigations.

PMID- 29066198
TI  - Reduction of Escherichia Coli using ceramic disk filter decorated by nano-TiO2: A
      low-cost solution for household water purification.
AB  - Lack of access to safe water is a challenge in many developing countries,
      especially in rural areas. It is urgent to develop cost-effective water
      purification technologies to guarantee drinking water safety in these areas. The
      present study investigated the reduction of Escherichia coli (E. coli) using
      ceramic disk filters (CDFs) decorated by nano-TiO2. The production of CDFs coated
      with nano-TiO2 in terms of rice-husk ratio, rice-husk particle size, heating hold
      time and nano-TiO2 mass fraction was optimized. The results show that the optimum
      conditions for CDFs with nano-TiO2 coating included rice-husk ratio of 29.03%,
      rice-husk particle size of 0.28mm, heating hold time of 1.41h and nano-TiO2 mass
      fraction of 2.21%. Additionally, the morphological and crystal phase
      characteristics of CDFs were revealed after the decoration by nano-TiO2. The
      effects of temperature, influent E. coli concentration, lamp power and their
      interactions were explored via factorial analysis. Influent E. coli concentration
      and lamp power had significant effects on E. coli removal efficiency. This study
      provided the solid theoretical support for understanding the production and
      bacteria inactivation relevant to CDFs impregnated with nano-TiO2. The results
      have important implications for finding a safe and cost-effective approach to
      solve drinking water problems in developing countries.

PMID- 29066199
TI  - Utility of ASTER and Landsat for quantifying hydrochemical concentrations in
      abandoned gold mining.
AB  - The effect of mining on water resources is severe and requires careful monitoring
      and management. Remote sensing has been used to characterize water quality
      indicators in efforts to fight mine-induced contamination. Much focus has however
      been placed on producing a qualitative classification of water qualities.
      Moreover, the number of variables considered in most studies is relatively small
      for a large number of hydrochemical constituents common in water bodies
      associated with gold mining activities. This study is aimed at quantifying a
      comprehensive list of field- and laboratory-measured chemical constituents of
      water samples from abandoned mines using remotely-sensed data. Akaike's
      Information Criterion was used to estimate each of the constituents using
      statistical values derived from individual bands of ASTER and Landsat data as
      predictors. Fairly good accuracies were obtained for constituents such as redox
      potential (Eh), major anions and cations. In contrast, trace elements correlated
      poorly with ASTER and Landsat bands, due mainly to a sampling anomaly. The
      performances of the two images in estimating the constituents were comparable.
      These findings suggest the potential of multispectral, moderate spatial
      resolution remote sensing for quantifying different hydrochemical properties of
      water bodies in mining environments. Further studies are however encouraged to
      enhance accuracies and reliability using a greater number of samples than was
      used in this study to capture the variability present in the population.

PMID- 29066200
TI  - Corrigendum to "Pesticide Toxicity Index-A tool for assessing potential toxicity
      of pesticide mixtures to freshwater aquatic organisms" [Sci. Total Environ. 476
      477 (2014) 144-157].

PMID- 29066203
TI  - Vermicompost and biochar as bio-conditioners to immobilize heavy metal and
      improve soil fertility on cadmium contaminated soil under acid rain stress.
AB  - This experiment was conducted to investigate the remediation effects of bio
      conditioners vermicompost (VC) and biochar (BC) on cadmium contaminated soil
      under the threat of acid rain, individually and associatively. With the
      application of soil conditioners, the percentages of HOAc-extractable Cd
      decreased 5.2-6.8%, 9.0-13.5% and 7.9-12.1% in the groups amended with VC, BC and
      VC combined BC, respectively. When the pH of rain decreased from 7.0 to 4.0, the
      activity of acid phosphatase decreased 2.0%, 12.3%, 3.2%, 14.8% in VC, BC, VC
      combined BC and control groups, individually. This study affirmed that with the
      application of soil conditioners, the threat of heavy metal along with
      bioavailability of Cd was depressed, and the properties of soil biochemical
      indictors were enhanced. Oppositely, the bioavailability of Cd was promoted, and
      soil microbial viability as well as nutrient contents was inhibited with the
      spraying of acid rain. The findings indicated that acid deposition played a
      restrain effect on soil remediation process. Meanwhile, soil conditioners showed
      potentials to improve soil fertilities and alleviate the stress of acid rain.

PMID- 29066201
TI  - Insights into extinction evolution during extreme low visibility events: Case
      study of Shanghai, China.
AB  - Apportionment of ambient extinction coefficient is essential for quantifying the
      causes of visibility degradation. Previous studies focused on either seasonal or
      episode-average extinction coefficients. The extinction evolution during
      different types of low visibility events was still unclear and seldom
      investigated. In this study, hourly-resolution apportionment of ambient
      extinction coefficient, including dry extinction coefficient and hygroscopic
      portion, during three low visibility events (i.e., dust storm, autumn and winter
      haze) and one clear episode was retrieved through online measurement in Shanghai,
      China. PM2.5 soil and coarse particles contributed 90% of PM10 mass and 62% of
      total extinction coefficient throughout the dust storm event. Secondary inorganic
      aerosol and organic matter dominated the autumn and winter haze events,
      accounting for 52% and 31% of PM2.5 mass, 35% and 27% of extinction coefficient,
      respectively. Hygroscopic enhancement by inorganic particles contributed another
      22-27% of extinction coefficient during the two haze events. However, higher
      relative humidity elevated the extinction percentage of inorganic aerosol and
      hygroscopic enhancement during the autumn haze, and the percentage of organic
      matter decreased correspondingly. In contrast, the extinction of each contributor
      increased proportionally and the percentages could keep at a stable level during
      the winter haze. Furthermore, the mass extinction efficiency of major PM2.5
      chemical components was found to increase with the accumulation of mass loading.
      These findings indicated the importance of reducing the mass level of organic
      matter and secondary inorganic aerosol during the autumn or winter haze events.
      The control of precursors of sulfur and nitrogen oxides seemed more effective for
      visibility improvement during the autumn events with higher relative humidity.

PMID- 29066202
TI  - Phosphorous fractions in soils of rubber-based agroforestry systems: Influence of
      season, management and stand age.
AB  - Rubber-based agroforestry system is a vital management practice and its
      productivity is often controlled by soil phosphorus (P) nutrient, but little
      information is available on P fractions dynamics in such system. The aim of this
      study was to examine the seasonal, management and stand age effects on P
      fractions, acid phosphatase activity, microbial biomass P, other physical
      chemical properties and litter and roots in four systems: 10-year-old rubber mono
      (YM) and intercropping (YI) with N-fixing species (NFS), 22-year-old mono- (MM)
      and intercropping (MI) in Xishuangbanna, Southwestern China. Most P fractions
      varied seasonally at different depths, with highest values in the fog-cool season
      (i.e. labile P at 5-60cm, non-labile P and total P at 30-60cm). By contrast,
      moderately labile P varied little over time, except in MI that had lower values
      in the rainy season. Compared with their monoculture counterparts, YI doubled
      resin-Pi concentration but decreased NaHCO3-extractable P, HCl-Pi and residual-Po
      at the 0-30cm depth, whereas MI had hardly any changes in P species at the 60-cm
      depth. Surprisingly, residual-Po was enriched down to the deepest soil (30-60cm)
      in both YI and MI in the fog-cool season. All P fractions, except NaOH0.1-Pi,
      were greatly reduced with increasing stand age. In addition to plants uptake,
      these changes can be explained by seasonality in soil environments (e.g.
      moisture, temperature, pH and microbial activity) and decomposition of litter and
      roots. Moreover, YI decreased labile Po stock, but MI increased moderately labile
      Pi at the 60-cm depth across seasons. The results imply that a large amount of
      residual-Po exists in acidic Oxisol from China and that they can be reasonably
      exploited to reduce the application of P fertilizers, highlighting the importance
      of Po pool. Taken together, intercropping mature rubber plantation with NFS
      appears to be an effective way to enhance productivity while maintaining adequate
      soil P concentration over the long run.

PMID- 29066204
TI  - Morphological, proteomic and metabolomic insight into the effect of cerium
      dioxide nanoparticles to Phaseolus vulgaris L. under soil or foliar application.
AB  - Chemically synthesized nanoparticles (NPs) are widely used in industry and
      concern over their impact on the environment is rising. In this study, greenhouse
      grown bean (Phaseolus vulgaris L.) plants were treated with CeO2 NPs suspensions
      at 0, 250, 500, 1000, and 2000mgL-1 either aerially by spraying or via soil
      application. At 15days after treatment, plants were analyzed for Ce uptake,
      morphological and biochemical assays, as well as high-resolution mass
      spectrometry based metabolomics and proteomics. The results from ICP-MS assays
      showed a dose dependent absorption, uptake and translocation of Ce through both
      roots and leaves; Ce content increased from 0.68 up to 1894mgkg-1 following spray
      application, while concentrations were three orders lower following soil
      application (0.59 to 2.19mgkg-1). Electrolyte leakage increased with NPs rate,
      from 25.2% to 70.3% and from 24.8% to 32.9% following spray and soil application,
      respectively. Spraying lowered stomatal density (from 337 to 113 per mm2) and
      increased stomatal length (from 12.8 to 19.4MUm), and altered photosynthesis and
      electron transport chain biochemical machinery. The increase in Ce content
      induced accumulation of osmolites (proline increased from 0.54 to 0.65mg/g under
      spray application), phytosiderophores (muconate and mugineate compounds showed
      increase fold-changes >16) and proteins involved in folding or turnover. NPs
      application induced membrane damage, as evidenced by the increase in membrane
      lipids degradates and by the increase in electrolyte leakage, and caused
      oxidative stress. Most of the responses were not linear but dose-dependent,
      whereas metabolic disruption is expected at the highest NPs dosage. Both
      proteomics and metabolomics highlighted a stronger effect of CeO2 NPs spraying,
      as compared to soil application. High concentrations of NPs in the environment
      have been confirmed to pose toxicity concern towards plants, although important
      differences could be highlighted between aerial deposition and soil
      contamination.

PMID- 29066205
TI  - Protonation-dependent heterogeneity in fluorescent binding sites in sub-fractions
      of fulvic acid using principle component analysis and two-dimensional correlation
      spectroscopy.
AB  - Heterogeneous distributions of proton binding sites within sub-fractions of
      fulvic acid (FA3-FA13) were investigated by use of synchronous fluorescence
      spectra (SFS), combined with principle component analysis (PCA) and two
      dimensional correlation spectroscopy (2D-COS). Tryptophan-like, fulvic-like and
      humic-like materials were observed in SFS. Tyrosine-like materials were
      identified by use of SFS-PCA analysis. Combined information from synchronous
      asynchronous maps and dissociation constants (pKa) was used to describe
      heterogeneity of binding sites for protons within each sub-fraction.
      Heterogeneous distributions of proton binding sites were observed in fulvic-like,
      humic-like, tryptophan-like, and tyrosine-like materials of five sub-fractions
      and even in the single fulvic-like materials in FA3 and tryptophan-like materials
      in FA9 and FA13. Values of pKa of sub-fractions ranged from 2.20 to 5.29,
      depending on associated wavelengths in synchronous-asynchronous maps and use of
      the modified Stern-Volmer equation. The larger values of pKa (4.17-5.29) were
      established for protein-like materials (including tryptophan-like and tyrosine
      like materials) in comparison to those (2.20-3.38) for humic-like and fulvic-like
      materials in sub-fractions. Sequential variations of 274nm (pKa 4.15-5.29)->360
      460nm (pKa 2.78-2.39) for FA5-FA13 revealed that binding of protons to tryptophan
      like materials appeared prior to humic-like/fulvic-like materials. In FA9,
      protons were preferentially binding to tryptophan-like materials than tyrosine
      like materials. In FA3, protons were preferentially binding to humic-like
      materials than fulvic-like materials. Relative differences of values of pKa for
      fluorescent materials within each sub-fraction were consistent with sequential
      orders derived from asynchronous maps. Such an integrated approach, SFS-PCA/2D
      COS, has superior potential for further applications in exploring complex
      interactions between dissolved organic matter and contaminants in engineered and
      natural environments.

PMID- 29066206
TI  - The ongoing quest for understanding the novel environmental applications and
      implications of nanotechnology.

PMID- 29066207
TI  - Public health risk assessment with bioaccessibility considerations for soil PAHs
      at oil refinery vicinity areas in India.
AB  - Populations living in the vicinity of oil refinery sludge deposition sites may be
      at greater risk of potential exposure to polycyclic aromatic hydrocarbons (PAHs)
      through inhalation, ingestion, and direct contact with contaminated media. Three
      Indian oil refinery sludge deposition sites (at Haldia, Barauni and Guwahati)
      were chosen for study. Soil samples were collected from three different locations
      at each site. Mild solvent extraction by butanol and exhaustive extraction by
      acetone/hexane have been conducted to estimate the bioaccessible PAHs beside the
      total extractable PAHs content of the soil samples. Concentrations of 13 PAHs in
      the soils were found to be in a range of 67.02-95.21MUg/g and bioaccessible PAHs
      were in a range of 19.296-36.657MUg/g. A probabilistic health risk assessment
      with bioaccessibility considerations was carried out using Monte Carlo
      simulations for the estimation of the cancer risk exposed to the PAHs. The 90th
      percentiles cancer risks with bioaccessibility considerations of soil PAHs for
      children is 6.506E-05 and for the adults the risk is 6.609E-05. Risk assessments
      on extracted PAHs from exhaustive solvent extraction can overestimate the risk by
      2.87-2.89 folds at 90% confidence level with respect to the biomimetic mild
      extraction procedure using butanol. According to USEPA above 1*10-6 extra risk of
      cancer is an alarm towards management. So, public health issues due to PAHs is
      imminent in these oil refinery vicinity areas. Sensitivity analysis revealed
      exposure duration (ED) and relative skin adherence factor for soil (AF) as the
      most influential parameters of the assessment. The profiling and risk assessment
      study with bioaccessibility considerations of PAHs from soil indicates that high
      PAHs concentration can lead to higher cancer risk for the vicinity area residents
      and local government should take immediate management actions.

PMID- 29066208
TI  - A multicomponent kinetic model established for investigation on atmospheric new
      particle formation mechanism in H2SO4-HNO3-NH3-VOC system.
AB  - Secondary new particle formation (NPF) plays a significant role in atmospheric
      particulate matters (e.g., PM2.5), and has been studied over the past decades.
      However, the mechanism of NPF still remains ambiguous, setting significant
      barrier for PM2.5 mitigations, especially in complex atmosphere with multi
      pollutants. Since the NPF process can hardly be observed directly by experiment
      methods due to the measuring limitations, a multicomponent kinetic model (MKM),
      which can be used to analyze the process and the mechanism of NPF in H2SO4-HNO3
      NH3-VOC (Volatile Organic Compounds) system, has been developed in this paper.
      According to MKM, seven cases with initial concentrations of total precursor
      vapors (CPV) in the range of 107-108cm-3 were calculated to analyze the NPF
      process. Firstly, the 3nm particle (PM3nm) formation rate was calculated via MKM,
      which showed a good agreement with the previous measurements. Moreover, according
      to MKM calculation, it is found that the peak value of PM3nm formation rate,
      i.e., Jm, is proportional to [CPV]2, while the time at which Jm occurred, i.e.,
      tm, is proportional to [CPV]-1/3, indicating that the increases in CPV would lead
      to a significant increase of Jm and decrease of tm. That's why NPF bursts
      immediately and PM2.5 pollution occurs suddenly in heavily pollutant areas.
      Afterwards, the roles of precursors in H2SO4-HNO3-NH3-VOC system were identified.
      It indicates that H2SO4, NH3 and VOC mainly contribute to the early stage of the
      NPF, while the growth of the nuclei is mainly driven by HNO3 and NH3. And HNO3
      makes increasing contributions at the early stage of NPF with CPV rising
      (especially above 108cm-3). Thus in high CPV areas, especially for China, HNO3
      should be paid the same attention as H2SO4, NH3 and VOC. The findings provide
      important implications for haze mitigations in China and other industrializing
      countries with multi-pollutant emission sources.

PMID- 29066209
TI  - Changes in glucose-lowering drug use before and after cancer diagnosis in
      patients with diabetes.
AB  - AIM: This study explores the changes in glucose-lowering drug (GLD) use before
      and after cancer diagnosis among patients with diabetes. METHODS: New GLD users
      (1998-2011) living in the Dutch ECR-PHARMO catchment area were selected from the
      PHARMO Database Network (n=52,228). Those with a primary cancer diagnosis were
      considered cases (n=3281) and matched with eligible controls (n=12,891) without
      cancer during follow-up. Conditional logistic regression analysis was used to
      assess changes in GLD use, such as treatment add-ons, treatments drops and
      initiation of insulin, for cases compared with controls associated with specific
      cancer types in four time windows (6-3 and 0-3months before cancer diagnosis; 0-3
      and 3-6months after cancer diagnosis). RESULTS: In the 3months before cancer
      diagnosis, patients with upper gastrointestinal (GI) cancers (oesophageal,
      stomach, pancreatic, liver cancers) had higher odds of initiating insulin (OR:
      9.3; 95% CI: 3.6-24.1); to a lesser extent, this was also observed in the 3months
      prior to that (at 6months, OR: 3.9; 95% CI: 1.3-12.1). Diagnosis of colorectal
      (OR: 3.4; 95% CI: 1.4-8.4), pulmonary (OR: 2.5; 95% CI: 1.1-5.4) and upper GI
      (OR: 13.6; 95% CI: 5.0-36.9) cancers was associated with increased odds of
      initiating insulin in the 3months after cancer diagnosis. During all study time
      windows, the odds of treatment drops were higher for patients with upper GI
      cancers whereas, for most other cancers, these odds were higher only after a
      diagnosis of cancer. CONCLUSION: The greater odds of initiating insulin during
      the 6months prior to diagnosis of upper GI cancers suggest reverse causation.
      After cancer diagnosis, drops in use of GLDs was commonly seen.

PMID- 29066210
TI  - Metabolomics in gestational diabetes.
AB  - Gestational diabetes mellitus (GDM) is a form of diabetes that is first diagnosed
      during pregnancy in the absence of existing type 1 or type 2 diabetes. Early
      screening tools for GDM are currently unavailable, but metabolomics is a
      promising approach for detecting biomarkers of GDM. This review evaluates recent
      GDM studies employing metabolomic techniques, highlighting the challenges in
      those studies and envisions the future directions for metabolomic study of GDM. A
      diverse range of predictive markers and dysregulated metabolic pathways have been
      associated with the pathogenesis of GDM, but these findings have lacked
      reproducibility among studies. The case-control study design has been most
      frequently employed in the studies of GDM, and most of them used specimens
      acquired in mid-pregnancy. However, this approach might not be adequate to
      recognise the complexity of the condition. The sample size in some of the studies
      is limited, and this may result in findings from a participant set that is not
      representative of the general population. Therefore, we propose that future
      metabolomic studies pertaining to GDM use a cross-platform approach employing
      unified diagnostic criteria, a longitudinal cohort, and innovative data
      processing methods to allow for full-scale identification and comprehensive
      coverage of the metabolome. In addition, the relationship between the exposure to
      environmental chemicals such as endocrine disruptors and the development of GDM
      should be further investigated in future studies.

PMID- 29066211
TI  - LncRNA PANDAR as a prognostic marker in Chinese cancer.
AB  - BACKGROUND: LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR)
      is reportedly dysregulated in various cancers. We performed this meta-analysis to
      clarify the efficacy of PANDAR as a prognostic marker in malignant tumors.
      METHODS: The PubMed, Medline, OVID, Cochrane Library, and Web of Science
      databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and
      95% confidence intervals (CIs) were calculated to explore the relationship
      between PANDAR expression and overall survival (OS). Odds ratios (ORs) were
      calculated to assess the association between PANDAR expression and pathological
      parameters. RESULTS: Eight original studies covering 1,132 cancer patients were
      included. The pooled HR suggested that high PANDAR expression correlated with
      poor OS (pooled HR=1.60, 95% CI: 1.09-2.33) in cancer patients. PANDAR expression
      was also related to lymph node metastasis (OR=3.26, 95% CI: 2.09-5.09), advanced
      tumor stage (OR=3.60, 95% CI: 2.39-5.44) and histological grade (OR=2.75, 95% CI:
      1.73-4.38). Begg's funnel plot showed no evidence of obvious asymmetry for
      overall survival and lymph node metastasis. CONCLUSIONS: Thus high PANDAR
      expression appears predictive of poor OS, lymph node metastasis, advanced tumor
      stage and histological grade in multiple cancers. This suggests PANDAR expression
      could serve as a biomarker of poor prognosis in Chinese cancer patients.

PMID- 29066212
TI  - Yes, there is still a place for on-call nighttime surgery for acute appendicitis!

PMID- 29066213
TI  - 99mTc by 99Mo produced at the ENEA-FNG facility of 14MeV neutrons.
AB  - A severe supply crisis of 99Mo, precursor of 99mTc a diagnostic radionuclide
      largely used in Nuclear Medicine, occurred in 2008-2009 due to repeated shut-down
      of the two main (aged) fission reactors. An alternative route for producing 99Mo
      by 100Mo(n,2n)99Mo reaction was investigated at ENEA. The experiment, designed
      according to Monte Carlo simulations performed with the Fluka code, produced 99Mo
      by irradiating a natural Molybdenum powdered target with 14MeV neutrons produced
      at the Frascati Neutron Generator. The 99Mo specific activity was measured at
      metrological level by gamma-ray spectrometry.

PMID- 29066214
TI  - Extended utilization of a 68Ge/68Ga reference source as a mock 18F source in the
      ionization chamber calibration.
AB  - Possible extended utilization of a 68Ge/68Ga source as a surrogate 18F reference
      source was studied. Some effects and uncertainties might arise from the
      difference of constructions between chambers that were used in the source
      calibration and those practically in use. To extend utilization of the surrogate
      source, response ratio of real 18F to 68Ge/68Ga sources were determined for three
      models of chambers. Monte-Carlo simulation using EGS5 code was also carried out
      to evaluate uncertainties expected. The present result shows that such a
      surrogate source would adapt to calibration even for chambers have with different
      construction from the reference chamber used as the determination of 18F
      equivalent activity of the 68Ge/68Ga surrogate source.

PMID- 29066215
TI  - Treatment with long acting muscarinic antagonists stimulates serum levels of
      irisin in patients with COPD.
AB  - Long acting muscarinic antagonists (LAMA) are currently considered the
      therapeutic mainstay for patients with COPD and have been shown to improve
      clinical outcomes including symptoms, exercise capacity and airflow limitation.
      Irisin, is a newly discovered hormone-like myokine generated by skeletal muscle
      cells in response to exercise and it is suggested to regulate energy expenditure
      and exercise capacity. The aim of the present study was to investigate if
      treatment with LAMA alters serum irisin levels in patients with COPD. Irisin was
      assessed by ELISA in the serum of 506 patients with COPD, GOLD II-IV, with a
      smoking history >10 PY, who were included in the PROMISE-COPD cohort. The effect
      of inhaled LAMA on serum irisin levels was evaluated in a proof-of-concept cohort
      of 40 COPD patients. Univariate linear regression analysis revealed that there
      was a significant negative association of irisin with age-adjusted Charlson score
      (p = 0.003) and a positive association of irisin with 6-min walking distance
      (6MWD) (p = 0.018) and treatment with LAMA (p = 0.004) but not with LABA or ICS.
      Multivariate analysis revealed that the association of irisin with LAMA treatment
      remains significant after adjustment for age-adjusted score and 6MWD. In the
      proof-of-concept cohort a single inhalation of LAMA stimulated serum irisin
      levels after 4 h. These findings imply that treatment of COPD patients with LAMA
      increase circulating irisin, thus explaining some of the beneficial extra
      pulmonary effects of these drugs when used in the treatment of COPD.

PMID- 29066216
TI  - Performance of the GenoType MTBDRsl assay for the detection second-line anti
      tuberculosis drug resistance.
AB  - The rapid detection of drug-resistant tuberculosis (TB) is important to improve
      treatment outcomes and prevent disease transmission. The GenoType MTBDRsl assay
      (MTBDRsl assay) was developed to detect fluoroquinolone (FQ) and second-line
      injectable drug (SLID) resistance. The aim of this study was to evaluate the
      performance and clinical utility of MTBDRsl assay. We retrospectively reviewed
      patient medical records with MTBDRsl assay data between December 2011 and
      February 2017. MTBDRsl assay results were compared with that of phenotypic drug
      susceptibility testing. In addition, treatment outcomes were analyzed to evaluate
      the clinical utility of the MTBDRsl assay. Among 107 clinical isolates (84
      cultured isolates and 23 sputum specimens), 85 (79.4%) were multidrug-resistant
      TB and 9 (8.4%) were extensively drug-resistant TB (XDR-TB). The sensitivity,
      specificity, positive predictive value (PPV), negative predictive value (NPV),
      and accuracy of MTBDRsl assay for detecting FQ resistance was 87.5%, 94.7%,
      87.5%, 94.7%, and 92.5%, respectively. The sensitivity, specificity, PPV, NPV,
      and accuracy of MTBDRsl assay for detecting SLID resistance was 88.9%, 98.9%,
      94.1%, 97.8%, and 97.2%, respectively. Novel drugs such as bedaquiline and
      linezolid were more commonly used in patients with FQ or SLID resistance detected
      by the MTBDRsl assay and, probably therefore, the treatment outcome was favorable
      irrespective of FQ or SLID resistance. The MTBDRsl assay could be used as a rule
      in test to detect FQ and SLID resistance. By detecting FQ- and SLID-drug
      resistance rapidly, novel or repurposed drugs could be initiated earlier,
      suggesting that better treatment outcomes would be expected in patients with pre
      XDR- and XDR-TB.

PMID- 29066217
TI  - Impact of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI
      LCBI) on central line-associated bloodstream infections (CLABSIs) in department
      of hematology at single university hospital in Japan.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are among
      the most serious complications especially in blood cancer patients. In January
      2013, Centers for Disease and Prevention (CDC) introduced a new surveillance
      definition of mucosal barrier injury-associated laboratory-confirmed bloodstream
      infection (MBI-LCBI). This study was to determine the impact of MBI-LCBI on
      CLABSIs and compare the clinical characteristics of MBI versus non-MBI-LCBI
      cases. PATIENTS AND METHODS: We retrospectively reviewed the records of 250
      consecutive patients. They were admitted in department of hematology at Aichi
      Medical University Hospital. We applied the revised 2013 CLABSI surveillance
      protocol to all CLABSI cases identified during the 47-months period from May 2012
      through June 2016. RESULTS: A total of 44 CLABSIs were identified. The median
      patient age was 65 years (range, 12 to 89). Among 44 patients, 31 patients were
      diagnosed as leukemia (70.5%) and 12 patients as lymphoma (27.3%). Six patients
      underwent bone transplantation for leukemia or myelodysplastic syndrome (13.6%).
      A total of 20 patients (45.5%) were classified as MBI-LCBI and 24 (54.5%) were
      classified as non-MBI-LCBI. The primary disease type (P = 0.018), neutropenic
      within 3 days before CLABSI (MBI-LCBI vs. non-MBI-LCBI: 95.0% vs. 26.3%, P =
      <0.0001), line(s) removed owing to CLABSI (15.0% vs. 54.2%, P = 0.011) and Gram
      negative organisms cultured (70.0% vs. 37.5%, P = 0.004) showed significantly
      difference between the groups. CONCLUSION: Our data showed that MBI-LCBI cases
      account for 45.5% of the CLABSI cases identified in blood cancer patients, and
      constituted a significant burden to this high-risk patient population.

PMID- 29066218
TI  - Emergence of ArmA, a 16S rRNA methylase in highly aminoglycoside-resistant
      clinical isolates of Klebsiella pneumoniae and Klebsiella oxytoca in Okinawa,
      Japan.
AB  - This study describes highly aminoglycoside-resistant Klebsiella pneumoniae and
      Klebsiella oxytoca clinical isolates obtained from an inpatient in Okinawa,
      Japan, with no known record of traveling overseas. The minimum inhibitory
      concentrations of amikacin and arbekacin against these strains were >1024 MUg/ml.
      Whole-genome sequencing analysis revealed that these isolates harbored armA,
      which encodes a 16S rRNA methylase, ArmA, that confers pan-aminoglycoside
      resistance. This is the second report of K. pneumoniae harboring armA and the
      first report of K. oxytoca harboring a 16S rRNA methylase encoding gene in Japan.

PMID- 29066219
TI  - A randomized controlled trial of one bag vs. two bag system of fluid delivery in
      children with diabetic ketoacidosis: Experience from a developing country.
AB  - PURPOSE: To compare one vs. two bag system with respect to blood glucose
      variability (BGV), time for resolution of acidosis and incidence of hypoglycemia,
      hypokalemia, and cerebral edema in children with diabetic ketoacidosis (DKA).
      MATERIAL AND METHODS: In an open labelled randomized controlled trial, thirty
      consecutive patients <=12years with DKA were randomized to either one (n=15) or
      two bag (n=15) system of intravenous fluid delivery. The two bags had similar
      electrolyte but differing dextrose concentration (none vs. 12.5%) and changing
      the rate of fluid, delivered different dextrose concentrations. BGV was primary
      outcome while hypoglycemia (blood glucose, BG<50mg/dL), hypokalemia (serum
      potassium<3.5mEq/L), time to resolution of acidosis and cerebral edema were
      secondary outcomes. RESULTS: The one and two bag systems had similar BGV
      parameters; median hourly absolute BG change (mg/dL) [44 (30-74.5) vs. 36 (31
      49); p=0.54], mean of standard deviation of BG measurements [65.1 (25.1) vs. 65.5
      (26.8); p=0.96] and median number of undesirable events (hourly blood sugar
      change >=50mg/dL) [4.5 (1.75-6.0) vs. 5.0 (3.0-8.0); p=0.31]. The incidence of
      hypoglycemia [42.9% (n=6) vs. 26.7% (n=4); p=0.45] and hypokalemia [64% (n=9) vs.
      67% (n=10); p=0.23], and mean (SD) time to resolution of acidosis [20.3 (14.8)
      and 20.3 (7.0); p=0.59] were similar in both the groups. None had cerebral edema.
      CONCLUSIONS: The one and two bag systems were similar to each other with respect
      to BGV, incidence of complications and time to resolution of acidosis.

PMID- 29066222
TI  - Prognostic Effect of Lymphovascular Invasion on TNM Staging in Stage I Non-Small
      cell Lung Cancer.
AB  - INTRODUCTION: Lymphovascular invasion (LVI) is a known adverse prognostic factor
      for early-stage non-small-cell lung cancer (NSCLC). Nonetheless, the prognostic
      effect of LVI on TNM staging of stage I NSCLC remains inconclusive. We thus
      hypothesized that it might be better to upstage pathologic stage IA NSCLC with
      LVI to pathologic stage IB NSCLC. PATIENTS AND METHODS: Using a Cox proportional
      hazards model, we examined the effect of LVI on disease-specific survival (DSS)
      in stage IA versus stage IB disease in 660 consecutive patients with stage I
      NSCLC (598 with adenocarcinoma, 62 with squamous cell carcinoma) who had
      undergone complete resection. RESULTS: On univariable analysis of stage IA cases,
      vascular invasion (VI) was significantly associated with inferior DSS
      (univariable hazard ratio [HR], 3.39; 95% confidence interval [CI], 1.46-7.89; P
      = .005). In contrast, lymphatic invasion exhibited a tendency toward inferior DSS
      (univariable HR, 2.90; 95% CI, 0.97-8.66; P = .056). Multivariable analysis of
      DSS in stage IA cases identified VI as an independent significant prognostic
      factor (multivariable HR, 2.86; 95% CI, 1.58-5.18; P = .007). With VI, DSS was
      significantly poorer for stage IB than for stage IA patients without VI
      (univariable HR, 3.44; 95% CI, 1.67-7.09; P < .001). In contrast, no difference
      was observed between patients with stage IA and VI and stage IB patients (P =
      .97). CONCLUSION: The presence of VI independently and significantly affects DSS
      in patients with stage IA NSCLC. We found that stage IA with VI and stage IB
      disease had equivalent prognostic outcomes. Our results suggest that stage IA
      with VI should be upstaged to IB in the TNM classification of NSCLC.

PMID- 29066221
TI  - Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid
      joint.
AB  - 1,25-dihydroxyvitaminD3 (1,25(OH)2D3), has potent anti-inflammatory effects,
      including suppression of IL-17 + and IFNgamma+ T cells implicated in rheumatoid
      arthritis (RA), but efficacy at the site of active disease is unclear. To
      investigate this, T cells from synovial fluid (SF) and paired blood of patients
      with active RA were studied. 1,25(OH)2D3 had significantly less suppressive
      effect on Th17 cells (IL-17+IFNgamma-) and Th17.1 cells (IL-17+IFNgamma+) from SF
      compared to those from blood, and had no effect on SF CD4+ or CD8+ IFNgamma+ T
      cell frequencies. Memory T cells (CD45RO+) predominate in SF, and 1,25(OH)2D3 had
      less effect on memory T cells relative to naive (CD45RA+) T cells. RT-PCR and
      flow cytometry showed that this was not due to decreased expression of the
      vitamin D receptor or its transcription partners in memory T cells. Further
      studies using stimulated CD4+ T cells sorted according to IL-17 and IFNgamma
      expression confirmed the ability of 1,25(OH)2D3 to suppress pre-existing
      cytokines. However, 1,25(OH)2D3 was most effective at suppressing de novo IL-17
      and IFNgamma induction. Correspondingly, T cell responses to 1,25(OH)2D3
      correlated directly with capacity for phenotype change, which was lower in cells
      from SF compared to blood. These findings indicate that anti-inflammatory effects
      of 1,25(OH)2D3 in active RA are impaired because of reduced effects on phenotype
      committed, inflammatory memory T cells that are enriched in SF. Restoration of
      1,25(OH)2D3 responses in memory T cells may provide a new strategy for treatment
      of inflammatory diseases such as RA.

PMID- 29066220
TI  - De-adhesion dynamics of melanoma cells from brain endothelial layer.
AB  - Metastasis formation is a complex and not entirely understood process. The
      poorest prognosis and the most feared complications are associated to brain
      metastases. Melanoma derived brain metastases show the highest prevalence. Due to
      the lack of classical lymphatic drainage, in the process of brain metastases
      formation the haematogenous route is of primordial importance. The first and
      crucial step in this multistep process is the establishment of firm adhesion
      between the blood travelling melanoma cells and the tightly connected layer of
      the endothelium, which is the fundamental structure of the blood-brain barrier.
      This study compares the de-adhesion properties and dynamics of three melanoma
      cells types (WM35, A2058 and A375) to a confluent layer of brain micro-capillary
      endothelial cells. Cell type dependent adhesion characteristics are presented,
      pointing towards the existence of metastatic potential related nanomechanical
      aspects. Apparent mechanical properties such as elasticity, maximal adhesion
      force, number, size and distance of individual rupture events showed altered
      values pointing towards cell type dependent aspects. Our results underline the
      importance of mechanical details in case of intercellular interactions.
      Nevertheless, it suggests that in adequate circumstances elastic and adhesive
      characterizations might be used as biomarkers.

PMID- 29066223
TI  - Application of Speckle-Tracking Echocardiography in an Experimental Model of
      Isolated Subendocardial Damage.
AB  - BACKGROUND: The subendocardium is highly vulnerable to damage and is thus
      affected even in subclinical disease stages. Therefore, methods reflecting
      subendocardial status are of great clinical relevance for the early detection of
      cardiac damage and the prevention of functional impairment. The aim of this study
      was to investigate the potential ability of myocardial strain parameters to
      evaluate changes within the subendocardium. METHODS: Male 129/Sv mice were
      injected with isoproterenol (ISO; n = 32) to induce isolated subendocardial
      fibrotic lesions or saline as appropriate control (n = 15). Transthoracic
      echocardiography was performed using a 30-MHz linear-frequency transducer coupled
      to a high-resolution imaging system, and acquired images were analyzed for
      conventional and strain parameters. The degree of collagen content within the
      different cardiac layers was quantified by histologic analysis and serum levels
      of tissue inhibitor of metalloproteinase-1, a biomarker for fibrosis, were
      assessed. RESULTS: ISO treatment induced a marked increase in subendocardial
      collagen content in response to cell loss (control vs ISO, 0.6 +/- 0.3% vs 5.8 +/
      0.9%; P < .001) and resulted in a moderate increase in left ventricular wall
      thickness with preserved systolic function. Global longitudinal peak strain (LS)
      and longitudinal strain rate were significantly decreased in ISO-treated animals
      (LS, -15.49% vs -11.49% [P = .001]; longitudinal strain rate, -4.81 vs -3.88 sec
      1 [P < .05]), whereas radial and circumferential strain values remained
      unchanged. Global LS was associated with subendocardial collagen content (r =
      0.46, P = .01) and tissue inhibitor of metalloproteinase-1 serum level (r = 0.52,
      P < .05). Further statistical analyses identified global LS as a superior
      predictor for the presence of subendocardial fibrosis (sensitivity, 84%;
      specificity, 80%; cutoff value, -14.4%). CONCLUSION: Assessment of LS may provide
      a noninvasive method for the detection of subendocardial damage and may
      consequently improve early diagnosis of cardiac diseases.

PMID- 29066225
TI  - Urinary Tissue Engineering: Challenges and Opportunities.
AB  - INTRODUCTION: In this review, we discuss major advancements and common challenges
      in constructing and regenerating a neo-urinary conduit (NUC). First, we focus on
      the need for regenerating the urothelium, the hallmark the urine barrier, unique
      to urinary tissues. Second, we focus on clinically feasible scaffolds based on
      decellularized matrices and molded collagen that are currently of great research
      interest. AIM: To discuss the major advancements in constructing a tissue
      engineered NUC (TE-NUC) and the challenges involved in their successful clinical
      translation. METHODS: A comprehensive search of peer-reviewed literature from
      PubMed and Google Scholar on subjects related to urothelium regeneration,
      decellularized tissue matrices, and collagen scaffolds was conducted. MAIN
      OUTCOME MEASURE: We evaluated the main biological and mechanical functions of
      urinary tissues, the need for TE implants to create a urinary diversion, the
      reasons for their failures in clinical settings, and the applications of
      decellularized tissue matrices and collagen-based molded scaffolds in their
      regeneration. RESULTS: It is necessary to create a urine barrier that prevents
      urine leakage into the stroma that can cause failure of the graft. Despite the
      regeneration potential of the urothelium, the limited supply of healthy
      urothelial cells in patients with bladder cancer remains a major challenge. In
      this context, alternative strategies, such as transdifferentiation of cells into
      urothelium or engineered scaffolds based on decellularized tissues and molded
      collagen with robust urine barrier properties, are active areas of research.
      CONCLUSION: There is an immediate need for developing a functional TE-NUC that
      can improve the quality of life of patients with bladder cancer. It is possible
      to achieve a TE-NUC by bioengineering an implant that has appropriate biological
      and mechanical properties to store and transport urine. We anticipate that future
      advancements in urothelium regeneration and material design will lead us closer
      to successful neo-urinary tissue constructs. Singh A, Bivalacqua TJ, Sopko N.
      Urinary Tissue Engineering: Challenges and Opportunities. Sex Med Rev 2018;6:35
      44.

PMID- 29066226
TI  - Cast Nephropathy and Deceptively Low Absolute Serum Free Light Chain Levels:
      Resolution of a Challenging Case and Systematic Review of the Literature.

PMID- 29066228
TI  - Primary trigeminal neuralgia is associated with posterior fossa crowdedness: A
      prospective case-control study.
AB  - Neurovascular conflict (NVC) has been postulated to be the underlying cause of
      trigeminal neuralgia (TN). Does the posterior fossa crowdedness increase the
      chance of NVC? The aim of this study was to quantitatively measure the posterior
      fossa crowdedness in patients with TN and to perform a comparison with healthy
      controls. We conducted a prospective case-control study of 46 patients diagnosed
      with primary TN and 46 sex- and age-matched healthy controls. All subjects
      underwent high-resolution three-dimensional MRI, and the 3D Slicer software was
      used to measure the posterior fossa volume (PFV) and hindbrain volume (HBV). The
      posterior fossa crowdedness index (PFCI) was calculated as HBV/PFV * 100%. The
      results showed that patients with TN had a larger HBV (155.4 +/- 23.2 cm3 versus
      152.9 +/- 13.5 cm3, P = .16) and a smaller PFV (182.7 +/- 18.3 cm3 versus 186.1
      +/- 11.7 cm3, P = .42) as compared to control subjects, but these values were not
      significantly different. The mean PFCI was significantly higher in patients with
      TN than in controls (85.1% +/- 3.4% versus 82.2% +/- 5.3%; P = .03). Women had a
      more crowded posterior fossa than men (85.8% +/- 2.1% versus 84.1% +/- 2.6%; P =
      .023) in patients with TN. The correlation analysis showed that a higher PFCI was
      associated with younger age (P = .02), woman (P = .014), and TN disease (P =
      .001). From this study, we conclude that patients with TN have a more crowded
      posterior fossa than healthy subjects. Women, younger age and TN disease are
      associated with a higher PFCI. The posterior fossa crowdedness may be a risk
      factor of NVC, and thus more likely to result in the genesis of TN.

PMID- 29066227
TI  - Improvement in venous-phase delay after superficial temporal artery to middle
      cerebral artery bypass.
AB  - The utility of superficial temporal artery to middle cerebral artery (STA-MCA)
      bypass before therapeutic internal carotid artery (ICA) occlusion is unclear. A
      65-year-old woman with a symptomatic giant left paraclinoid ICA aneurysm
      underwent endovascular ICA occlusion following STA-MCA double bypass.
      Preoperative balloon test occlusion (BTO) demonstrated a venous-phase delay of
      1.5 s. Only focal improvement in the venous-phase delay was observed immediately
      after treatment, but three-week postoperative angiography showed remarkable
      improvement of 0.5 s. To our knowledge, this is the first known case that
      demonstrates the effect of STA-MCA bypass on postoperative improvement in venous
      phase delay.

PMID- 29066229
TI  - Depression and cardiovascular disease in elderly: Current understanding.
AB  - Geriatric depression is a major public health problem and has an especially large
      effect on health when comorbid with a chronic medical condition. Hypertension,
      coronary heart disease, and diabetes are accompanied by a high incidence of
      depression and can affect the treatment and prognosis. Depression is a highly
      prevalent risk factor for incident of and is associated with morbidity and
      mortality of cardiovascular disease. In addition to the proactive and effective
      control of primary diseases, efforts should also be made to improve patients'
      psychological and social function. Current evidence on antidepressive therapy in
      patients with coronary diseases is limited. A better understanding of
      pathophysiological mechanisms underpinning depression and cardiovascular disease
      as well as the complex biological crosstalk of cardiovascular disease complicated
      with depression is particularly important for future therapeutic strategies. The
      following review is on current understanding of geriatric depression and
      cardiovascular disease.

PMID- 29066224
TI  - Oxytocin Receptors in the Anteromedial Bed Nucleus of the Stria Terminalis
      Promote Stress-Induced Social Avoidance in Female California Mice.
AB  - BACKGROUND: The neuropeptide oxytocin (OT) is a key regulator of social and
      emotional behaviors. The effects of OT are context dependent, and it has been
      proposed that OT increases the salience of both positive and negative social
      cues. Here we tested whether the bed nucleus of the stria terminalis (BNST)
      mediates anxiogenic effects of OT. METHODS: First, we studied the effects of
      systemic administration of an OT receptor (OTR) antagonist L-368,899 on social
      behavior in male and female California mice exposed to social defeat. We examined
      the effect of L-368,899 on G protein activation and used early growth response
      factor 1 immunohistochemistry to identify potential sites of OTR action. Finally,
      we examined the effects of L-368,899 infused in the BNST on behavior. RESULTS: A
      single dose of systemic L-368,899 increased social approach in stressed female
      mice and decreased social approach in male mice naive to defeat. L-368,899
      prevented OT activation of G proteins and did not activate G proteins in the
      absence of OT. Intranasal OT, which reduces social approach in female mice but
      not male mice, increased early growth response factor 1 immunoreactivity in the
      nucleus accumbens core and anteromedial BNST in female mice but not in male mice.
      Stressed female mice that received an infusion of L-368,899 into the anteromedial
      BNST but not the nucleus accumbens core increased social approach and decreased
      social vigilance responses. CONCLUSIONS: Our results suggest that OTR activation
      in anteromedial BNST induces a vigilance response in which individuals avoid, yet
      attend to, unfamiliar social contexts. Our results suggest that OTR antagonists
      may have unappreciated therapeutic potential for stress-induced psychiatric
      disorders.

PMID- 29066230
TI  - Intraoperative neurophysiologic monitoring (IONM) changes associated with a case
      of delayed thalamic infarct: Implications for postoperative management.
AB  - Treatment of cerebral aneurysms poses a risk of cerebral hemorrhage and/or
      ischemia; these potential sequelae are usually associated with changes in
      intraoperative neurophysiologic monitoring (IONM) modalities. Our case
      demonstrates a patient with significant changes in IONM during the treatment of a
      right posterior cerebral artery aneurysm who did not develop neurologic deficits
      until three days postoperatively. IONM changes can represent a guide in
      postoperative patient management and may pose grounds for closer monitoring of
      patients with IONM changes that do not develop immediate postoperative deficits.

PMID- 29066231
TI  - Antibiotic prophylaxis and infection prevention for endoscopic endonasal skull
      base surgery: Our protocol, results, and review of the literature.
AB  - Endoscopic endonasal approaches to the skull base provide minimally invasive
      corridors to intracranial lesions; however, enthusiasm for this new approach is
      always tempered by the recognition that this route requires passage through a
      nonsterile sinonasal corridor. Despite an increasing number of patients
      undergoing these surgeries, there remains no consensus on the use of
      perioperative antibiotics. A retrospective review of consecutive patients
      undergoing endoscopic endonasal skull base surgery (EESBS) at Loyola University
      Medical Center by the same neurosurgeon and otolaryngologist team between
      February 2015 and October 2016 was performed. Antibiotic regimens, presence of an
      intraoperative or postoperative cerebrospinal fluid (CSF) leak, dural
      reconstruction method, and rates of sinusitis, meningitis, and/or intracranial
      abscess were analyzed. 39 patients who underwent a total of 41 EESBSs with a mean
      age of 46 years were identified. A vascularized nasoseptal flap was used for
      dural reconstruction when high flow CSF leaks were encountered intraoperatively
      (n = 17); otherwise, reconstruction mostly consisted of allografts and/or free
      mucosal grafts. There were zero postoperative cases of CSF leaks, meningitis, or
      intracranial infection. Our current antibiotic prophylaxis protocol coupled with
      the use of variable dural reconstruction techniques dictated by intraoperative
      findings has led to low rates of postoperative CSF leaks, intracranial
      infections, and meningitis. A survey was also distributed to Neurological Surgery
      Residency Programs to gain a better understanding of the EESBS protocols that are
      being used nationally. The practice of antibiotic prophylaxis for patients
      undergoing EESBS is quite variable and this study should provide the impetus for
      multi-institutional comparison studies.

PMID- 29066232
TI  - Infections in neuromyelitis optica spectrum disorder.
AB  - Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory astrocytopathy
      that has both genetic and environmental causes. A growing body of evidence
      suggests that the presence of several infectious agents correlates with the
      development of NMOSD. In this review, we summarize studies that either support or
      present evidence against the hypothesized association between infection and
      NMOSD. We will also present an overview of potential mechanisms underlying the
      pathogenesis of NMOSD. Finally, we provide some beneficial properties that
      infectious elements may have based on "hygiene hypothesis". It is of great
      clinical significance to further investigate the complex mechanisms by which
      infections may affect autoimmune diseases to develop better strategies to prevent
      and treat them, although so far no causal link between infectious agents and
      NMOSD has been established.

PMID- 29066234
TI  - The trans-laminar terminalis approach reduces mortalities associated with
      chordoid glioma resections: A case report and a review of 20 years of literature.

PMID- 29066233
TI  - Comparative transcriptome analysis reveals involvement of TLR-2 signaling in the
      pathogenesis of intracranial aneurysm.
AB  - In this study, we collected and analyzed 15 aneurysmal and 17 superficial
      temporal artery (STA) specimens from 32 Chinese patients with intracranial
      aneurysm. Total RNA was extracted and reverse transcribed to cDNA, and genome
      wide expression profiling was performed by using the Affymetrix Human Genome U133
      Plus 2.0 Array which allows a total number of 38,500 genes to be analyzed at the
      same time. Real-time RT-PCR was performed to verify the expression level of 8
      selected genes. We found significant up-regulation of the TLR-2 gene. This result
      suggests that TLR-2 plays a key role in the formation of intracranial aneurysm in
      a Chinese population. To our knowledge, this study is the first to use the Human
      Genome U133 Plus 2.0 Array to analyze the gene expression profiles in Chinese
      patients with intracranial aneurysm.

PMID- 29066235
TI  - Pregabalin as a salvage preoperative treatment for refractory trigeminal
      neuralgia.
AB  - Only few studies have investigated the effectiveness of pregabalin (PGB)
      treatment for trigeminal neuralgia (TN). We aimed to retrospectively analyze the
      effectiveness of PGB treatment in refractory TN as a salvage treatment preceding
      surgery. Of 61 patients with TN refractory to prior treatment with carbamazepine
      (CBZ), we enrolled 33 patients in our study who agreed to receive PGB before they
      underwent surgery. The patients were divided into effective and ineffective
      groups depending on the patient-reported outcome. Correlations between
      effectiveness and clinical characteristics such as the age, sex, disease
      duration, initial CBZ responsiveness, the number of patients who underwent
      polytherapy with PGB and CBZ, final doses of CBZ and PGB at the time of
      evaluation, and the etiology of the neurovascular compression were statistically
      analyzed. Furthermore, a linear discriminant analysis was performed to predict
      effectiveness. TN was improved in 16 patients (48.5%) in the PGB-treatment group
      but none in patients without PGB-treatment. The final dose of PGB was 166.7 mg at
      the mean follow-up period of 5.5 months. Our results showed that age was the only
      factor that significantly differed between PGB-effective and ineffective groups.
      A logistic regression analysis also demonstrated that among all the clinical
      variables considered, only older age was significantly associated with
      effectiveness of PGB treatment. Effectiveness was correctly predicted at a
      threshold value of 62.7-years-old with 69.7% reliability. We suggest that PGB is
      useful, even at the low-dose, as a salvage preoperative treatment for patients
      with refractory TN, particularly for elderly patients.

PMID- 29066237
TI  - Huntington's disease-like 2 with an expansion mutation of the Junctophilin-3
      gene; first reported case from Botswana.
AB  - Huntington's disease-like 2 (HDL2) is a rare autosomal dominant progressive
      neurodegenerative disorder commonly seen in adults. It was first described in a
      large African-American family in the United States. HDL2 clinically resembles
      Huntington's disease (HD) and causes adult-onset relentlessly progressive
      movement, emotional and cognitive dysfunction. Onset is usually in the fourth
      decade with slow progression to death. We present a 47-year-old male Botswana
      native, with a four-year-history of chorea, slurred speech, mood instability,
      cognitive impairment and weight loss. Genetic testing reveals normal HTT gene but
      a heterozygous expansion mutation at the JPH3 locus, confirmatory of HDL2. Though
      some cases of HDL2 have been reported from neighboring South Africa, this is the
      first instance from Botswana. This report draws attention to the fact that HDL2
      exists among native Batswana, and even though clinically indistinguishable from
      HD, molecular testing can result in positive case identification.

PMID- 29066236
TI  - Translational gap in ongoing clinical trials for glioma.
AB  - Despite the vast amounts of information gathered about gliomas, the overall
      survival of glioma patients has not improved in the last four decades. This could
      partially be due to an apparent failure to include basic concepts of glioma
      biology into clinical trials. Specifically, attempts to overcome the limitations
      of the blood brain barrier (BBB) and the chemoresistance of glioma stem cells
      (GSCs) were seldom included (a phenomenon known as the translational gap, TG) in
      a study involving 29 Phase I/II clinical trials (P2CT) published in 2011. The aim
      of this study was to re-evaluate this finding with a new series of 100 ongoing,
      but still unpublished, P2CT in order to determine if there is a TG reduction. As
      indicators, we evaluated in each P2CT the number of drugs tested, concomitant
      radiotherapy, and the ability of drugs to pass the BBB and to target GSCs.
      Compared to clinical trials published in 2011, we found that while in OCT there
      is an increase in the number of P2CT using two drugs (from 24.1% to 44.9%), and
      an increase in the number of drugs able to pass the BBB (7.14% versus 64.29%) and
      target GSCs (0% versus 16.3%), there was a decrease in the number of P2CT using
      concomitant radiotherapy (34.5% versus 18.37%). Overall our results suggest that
      there is only a modest improvement regarding reducing the TG because the vast
      majority of ongoing P2CT are still not including well known concepts of glioma
      biology important for a successful treatment.

PMID- 29066238
TI  - Ocular features of multiple system atrophy.
AB  - The aim of this paper is to gain better understanding of the ocular
      manifestations of multiple system atrophy (MSA), a neurodegenerative disorder
      rarely studied in terms of its ophthalmologic features. We performed a
      retrospective case series (1/1/05-12/31/14) to search for patients seen at Mayo
      Clinic, Rochester, MN, who had mention of MSA in the medical record and an eye
      examination, which yielded 285 cases. Of the 285, we identified 39 cases of true
      MSA. Each of these 39 patients was further reviewed for ocular abnormalities
      potentially related to MSA. Ocular findings potentially attributable to MSA were
      found in 64% of patients. Most common were dry eye (N = 14), conjugate eye
      movement abnormalities (N = 13), and ocular misalignment (N = 7). One patient had
      dry eye and monocular diplopia from trichiasis due to cicatricial pemphigoid, one
      had bilateral optic atrophy, and one had Adie's tonic pupil. Conjugate eye
      movement abnormalities (33%) and ocular misalignment (18%) were more common in
      patients with MSA-C. Patients with ocular findings, excluding dry eye, had a
      significantly shorter lifespan from time of initial neurologic symptoms to death.
      Our study confirms conjugate eye movement abnormalities and misalignment are
      common ocular findings in patients with MSA. Bilateral optic atrophy and
      cicatricial pemphigoid are possibly attributable to the disease. Ocular
      manifestations in MSA predict a poor prognosis as these patients have a
      significantly shorter lifespan. Therefore, we recommend patients with MSA have a
      comprehensive neuro-ophthalmologic exam at time of diagnosis, and thereafter, to
      screen for eye findings that may indicate a shorter lifespan.

PMID- 29066239
TI  - Neurophysiological correlates of depressive symptoms in young adults: A
      quantitative EEG study.
AB  - BACKGROUND: There is an unmet need for practical and reliable biomarkers for mood
      disorders in young adults. Identifying the brain activity associated with the
      early signs of depressive disorders could have important diagnostic and
      therapeutic implications. In this study we sought to investigate the EEG
      characteristics in young adults with newly identified depressive symptoms.
      METHODS: Based on the initial screening, a total of 100 participants (n = 50
      euthymic, n = 50 depressive) underwent 32-channel EEG acquisition. Simple
      logistic regression and C-statistic were used to explore if EEG power could be
      used to discriminate between the groups. The strongest EEG predictors of mood
      using multivariate logistic regression models. RESULTS: Simple logistic
      regression analysis with subsequent C-statistics revealed that only high-alpha
      and beta power originating from the left central cortex (C3) have a reliable
      discriminative value (ROC curve >0.7 (70%)) for differentiating the depressive
      group from the euthymic group. Multivariate regression analysis showed that the
      single most significant predictor of group (depressive vs. euthymic) is the high
      alpha power over C3 (p = 0.03). CONCLUSION: The present findings suggest that EEG
      is a useful tool in the identification of neurophysiological correlates of
      depressive symptoms in young adults with no previous psychiatric history.
      SIGNIFICANCE: Our results could guide future studies investigating the early
      neurophysiological changes and surrogate outcomes in depression.

PMID- 29066240
TI  - Pitfalls in the diagnosis of pupil-sparing oculomotor nerve palsy without limb
      ataxia: A case report of a variant of Claude's syndrome and neuroanatomical
      analysis using diffusion-tensor imaging.
AB  - Midbrain infarction causing oculomotor nerve palsy with contralateral ataxia is
      named Claude's syndrome. Herein we report the case of a variant of Claude's
      syndrome, which shows pupil-sparing oculomotor nerve palsy without the
      accompanying neurological deficits other than subtle truncal ataxia. MRI and
      Diffusion Tensor Imaging revealed that midbrain infarction was located rostrally
      above the decussation of the superior cerebellar peduncle (SCP) and might have
      partially destructed the tectospinal tract, which resulted in the absence of limb
      ataxia and presence of subtle truncal ataxia. In this variant of Claude's
      syndrome, we should carefully assess truncal ataxia to avoid misdiagnosing it as
      isolated pupil-sparing oculomotor nerve palsy because the patient showed
      apparently normal gait and truncal ataxia was only revealed by unstable tandem
      gait.

PMID- 29066241
TI  - Neuroendoscopic evacuation of intraventricular empyema using a side-cutting
      aspiration device.
AB  - Pyogenic ventriculitis is a rare but severe post-neurosurgical complication. The
      infection is often resistant to antibiotic treatment alone. Continuous
      intraventricular irrigation has been suggested but the technique is cumbersome,
      increases the risk for secondary infection, and is inadequate in removing
      adherent purulence. We used a novel neuroendoscopic approach assisted with a side
      cutting aspiration device to treat four cases of post-neurosurgical pyogenic
      ventriculitis. Ventricular empyema was cleared in all patients and three of the
      four patients had favorable outcomes.

PMID- 29066242
TI  - Estimating risk of adverse cardiac event after vascular surgery using currently
      available online calculators.
AB  - BACKGROUND: The decision to proceed with vascular surgical interventions requires
      evaluation of cardiac risk. Recently, several online risk calculators were
      created to predict outcomes and to lead to a more informed conversation between
      surgeons and patients. The objective of this study was to compare and further
      validate these online calculators with actual adverse cardiac outcomes at a
      single institution. METHODS: All patients from January 2011 through December 2015
      undergoing carotid endarterectomy (CEA), infrainguinal lower extremity bypass,
      open abdominal aortic aneurysm (AAA) repair, and endovascular aneurysm repair
      (EVAR) on the vascular surgical service were included using the Society for
      Vascular Surgery Vascular Quality Initiative database at our health system.
      Additional information was collected through retrospective chart review. Each
      patient was entered through three online risk calculators: (1) the American
      College of Surgeons National Surgical Quality Improvement Program (NSQIP)
      estimates the risk of cardiac arrest and myocardial infarction (MI); (2) the
      Revised Cardiac Risk Index (RCRI) estimates risk of MI, pulmonary edema,
      ventricular fibrillation, primary cardiac arrest, and complete heart block; and
      (3) the Vascular Study Group of New England (VSGNE) Cardiac Risk Index estimates
      risk of postoperative MI only. Observed adverse cardiac events (ACEs) were
      compared with expected values for each calculator using a chi2 goodness-of-fit
      test. Institutional Review Board exemption was obtained. RESULTS: A total of 856
      cases were included: 350 CEAs, 210 infrainguinal bypasses, 77 open AAA repairs,
      and 219 EVARs. For CEA, no risk calculator showed statistically significant
      variation from the observed values (NSQIP, P = .45; RCRI, P = .17; VSGNE, P =
      .24). For infrainguinal bypass, NSQIP slightly underpredicted adverse events (P =
      .054), RCRI strongly underpredicted (P = .002), and VSGNE showed no difference (P
      = .42). For open AAA repair, NSQIP (P = .51) and VSGNE (P = .98) were adequate
      predictors, but RCRI strongly underpredicted the adverse events (P <= .0001).
      Finally, EVAR cardiac outcomes showed greater adverse events than predicted by
      all three calculators (NSQIP, P = .02; RCRI, P = .0002; and VSGNE, P = .025).
      Pooled data for the entire group documented that the VSGNE proved an accurate
      tool for prediction (P = .34), whereas ACEs were underpredicted by NSQIP (P =
      .0055) and RCRI (P <= .001). CONCLUSIONS: Although online cardiac risk
      calculators of adverse surgical events are easy to use and to reference in broad
      surgical decision-making, there is significant variability in their
      predictability at the procedure and institutional level. Our data suggest that
      ACEs often occur at a higher rate than expected on the basis of calculated risks
      profiles, thus creating a platform for future discussion about preoperative
      evaluation and postoperative care decision-making models.

PMID- 29066243
TI  - Sustained local delivery of high-concentration vancomycin from a hybrid
      biodegradable, antibiotic-eluting, nanofiber-loaded endovascular prosthesis for
      treatment of mycotic aortic aneurysms.
AB  - BACKGROUND: Endovascular repair for mycotic aortic aneurysm (MAA) is a less
      invasive alternative to open surgery, although the placement of a stent graft in
      an infected environment remains controversial. In this study, we developed hybrid
      biodegradable, vancomycin-eluting, nanofiber-loaded endovascular prostheses and
      evaluated antibiotic release from the endovascular prostheses both in vitro and
      in vivo. METHODS: Poly(D,L)-lactide-co-glycolide and vancomycin were dissolved in
      1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into nanofibrous
      tubes, which were mounted onto commercial vascular stents and endovascular aortic
      stent grafts. In vitro antibiotic release from the nanofibers was characterized
      using an elution method and high-performance liquid chromatography. Antibiotic
      release from the hybrid stent graft was analyzed in a three-dimensional-printed
      model of a circulating MAA. The in vivo drug release characteristics were
      examined by implanting the antibiotic-eluting stents in the abdominal aorta of
      New Zealand white rabbits (n = 15). RESULTS: The in vitro study demonstrated that
      the biodegradable nanofibers and the nanofiber-loaded stent graft provided
      sustained release of high concentrations of vancomycin for up to 30 days. The in
      vivo study showed that the nanofiber-loaded stent exhibited excellent
      biocompatibility and released high concentrations of vancomycin into the local
      aortic wall for 8 weeks. CONCLUSIONS: The proposed biodegradable vancomycin
      eluting nanofibers significantly contribute to the achievement of local and
      sustainable delivery of antibiotics to the aneurysm sac and the aortic wall, and
      these nanofibers may have therapeutic applications for MAAs.

PMID- 29066244
TI  - Reliability of assessing postural control during seated balancing using a
      physical human-robot interaction.
AB  - This study evaluated the within- and between-visit reliability of a seated
      balance test for quantifying trunk motor control using input-output data. Thirty
      healthy subjects performed a seated balance test under three conditions: eyes
      open (EO), eyes closed (EC), and eyes closed with vibration to the lumbar muscles
      (VIB). Each subject performed three trials of each condition on three different
      visits. The seated balance test utilized a torque-controlled robotic seat, which
      together with a sitting subject resulted in a physical human-robot interaction
      (pHRI) (two degrees-of-freedom with upper and lower body rotations). Subjects
      balanced the pHRI by controlling trunk rotation in response to pseudorandom
      torque perturbations applied to the seat in the coronal plane. Performance error
      was expressed as the root mean square (RMSE) of deviations from the upright
      position in the time domain and as the mean bandpass signal energy (Emb) in the
      frequency domain. Intra-class correlation coefficients (ICC) quantified the
      between-visit reliability of both RMSE and Emb. The empirical transfer function
      estimates (ETFE) from the perturbation input to each of the two rotational
      outputs were calculated. Coefficients of multiple correlation (CMC) quantified
      the within- and between-visit reliability of the averaged ETFE. ICCs of RMSE and
      Emb for all conditions were >=0.84. The mean within- and between-visit CMCs were
      all >=0.96 for the lower body rotation and >=0.89 for the upper body rotation.
      Therefore, our seated balance test consisting of pHRI to assess coronal plane
      trunk motor control is reliable.

PMID- 29066245
TI  - Effects of neostigmine or edrophonium on force of contraction when administered
      at a train-of-four ratio of 0.9 in anesthetized dogs.
AB  - OBJECTIVE: Anticholinesterase drugs may produce paradoxical neuromuscular block
      when administered at shallow levels of neuromuscular block. The objective of this
      study was to evaluate the effects of neostigmine and edrophonium when
      administered at near-complete reversal from nondepolarizing block in anesthetized
      dogs. STUDY DESIGN: Incomplete crossover, randomized, blinded experimental study.
      ANIMALS: A total of 12 Beagle dogs. METHODS: Each dog was anesthetized twice with
      propofol and maintained with isoflurane and dexmedetomidine. Intravenous (IV)
      vecuronium (0.1 mg kg-1) was administered. When the mechanographic train-of-four
      (TOF) ratio had spontaneously recovered to >=0.9, either neostigmine (0.04 mg kg
      1) or edrophonium (0.5 mg kg-1) was administered IV, preceeded by atropine.
      Changes in twitch height or TOF ratio were measured for the next 10 minutes.
      Recurarization was considered to be present if values decreased by >=10%.
      RESULTS: Data from four dogs in each treatment were excluded from analysis,
      resulting in data from five dogs administered both treatments, three dogs
      administered neostigmine and three dogs administered edrophonium. There was no
      difference between groups for age, weight, T1 and T4 twitch heights or TOF ratio
      values, before or after anticholinesterase administration. The TOF ratio
      decreased by 17% and 18% in two of the eight dogs administered neostigmine,
      resulting from a larger increase in T1 relative to T4. No reductions in
      individual twitch amplitudes were recorded in those dogs. When edrophonium was
      used, no cases of recurarization were observed. CONCLUSIONS AND CLINICAL
      RELEVANCE: The results support use of edrophonium for reversal of shallow
      neuromuscular block. The decreases in TOF ratio recorded after neostigmine does
      not necessarily indicate muscular weakness. Although the clinical implications
      are uncertain, the results suggest that, at these doses, edrophonium may be
      preferable to neostigmine for reversal of shallow neuromuscular block in dogs.

PMID- 29066246
TI  - Changes on serum and hepatic lipidome after a chronic cadmium exposure in Wistar
      rats.

PMID- 29066247
TI  - Letter to the Editor on "The AAHKS Clinical Research Award: What Are the Costs of
      Knee Osteoarthritis in the Year Prior to Total Knee Arthroplasty?"

PMID- 29066248
TI  - Comparison of Clinical Results and Injury Risk of Posterior Tibial Cortex Between
      Attune and Press Fit Condylar Sigma Knee Systems.
AB  - BACKGROUND: We compared clinical and radiographic results after total knee
      arthroplasty (TKA) using Attune and Press Fit Condylar Sigma, and investigated
      whether use of the current prosthesis increased injury risk to the tibial cortex
      in Asian patients. We also assessed whether a preoperative posterior tibial slope
      angle (PSA) is associated with the injury when using the current prosthesis.
      METHODS: The 300 TKAs with Attune (group A) were compared to the 300 TKAs with
      Press Fit Condylar Sigma (group B). Demographics were not different, except
      follow-up periods (24.8 vs 33.3 months, P < .001). The Western Ontario and
      McMaster Universities Index and range of motion were compared. A minimum distance
      between tibial component stem and posterior tibial cortex (mDSC) was compared.
      The correlation between preoperative PSA and mDSC was analyzed in group A.
      RESULTS: The postoperative Western Ontario and McMaster Universities Index and
      range of motion of group A were better than those of group B (17.7 vs 18.8, P =
      .004; 131.4 degrees  vs 129.0 degrees , P = .008). The mDSC was shorter in group
      A (6.3 vs 7.0 mm, P < .001), which made up a higher proportion of the high-risk
      group for posterior tibial cortical injury with an mDSC of <4 mm (20.0% vs 10.7%,
      P = .002). A negative correlation was found between the preoperative PSA and mDSC
      in group A (r = -0.205, P < .001). CONCLUSION: The TKA using the current
      prosthesis provided more satisfactory results than the TKA using the previous
      prosthesis. However, the injury risk to the posterior tibial cortex increased in
      the knees with a large PSA when using the current prosthesis for Asian patients.

PMID- 29066249
TI  - The Influence of Radiological Severity and Symptom Duration of Osteoarthritis on
      Postoperative Outcome After Total Hip Arthroplasty: A Prospective Cohort Study.
AB  - BACKGROUND: We aimed to investigate the influence of preoperative radiological
      severity and symptom duration of hip osteoarthritis (OA) on the postoperative
      functional outcome, quality of life, as well as abductor muscle strength after
      total hip arthroplasty (THA). METHODS: In this prospective cohort study, we
      studied 250 patients. Preoperatively, we evaluated the function with the Western
      Ontario and McMaster Universities Osteoarthritis (WOMAC) index and quality of
      life with euroqol-5D (EQ-5D). At 1 year after THA, the same scores and also hip
      abductor muscle strength were measured in 222 patients. We divided the cohort
      twice, first according to the radiological OA severity [Kellgren-Lawrence
      classification (KL)] and then according to the OA symptom duration. We
      investigated whether the preoperative KL class and symptom duration influenced
      the 1-year WOMAC (primary outcome measure) or EQ-5D and abductor muscle strength
      (secondary outcome measures). RESULTS: The crude results showed that KL class and
      symptom duration had no influence (P = .90 and P = .20, respectively) on the 1
      year WOMAC. Younger age, male gender, and lower body mass index were associated
      with a better function. Regarding 1-year EQ-5D, the crude results showed that
      body mass index and KL class had no influence (P = .83 and P = .39,
      respectively). The adjusted results showed that only age and gender influenced
      the postoperative EQ-5D. No influence of the tested factors was found on the 1
      year abductor muscle strength. CONCLUSION: Preoperative radiological OA severity
      and symptom duration had no influence on the outcome of THA and should probably
      not affect the decision about timing the operative intervention.

PMID- 29066250
TI  - Corrigendum to 'Silver-Impregnated Occlusive Dressing Reduces Rates of Acute
      Periprosthetic Joint Infection After Total Joint Arthroplasty' [Journal of
      Arthroplasty 32 (2017) 929-932].

PMID- 29066251
TI  - Wound Closure Techniques for Total Knee Arthroplasty: An Evidence-Based Review of
      the Literature.
AB  - BACKGROUND: This literature review is aimed at identifying the different methods
      for superficial and deep wound closure in total knee arthroplasty and evaluating
      their outcomes. We evaluated (1) closure time, (2) infection and other
      complication rates, and (3) local wound-related outcomes. METHODS: A thorough
      search of the literature was performed using 3 electronic databases. Inclusion
      criteria included manuscripts that were written in English and available in full
      text format. Reports were stratified into those that describe deep closure (7)
      and those that describe superficial closure (11). RESULTS: In superficial
      closure, staples may provide the fastest closure, adhesives, lower incidence of
      superficial complications, and subcuticular suture closures, greatest blood flow.
      In deep closure, barbed sutures may allow for faster closure time while providing
      similar postoperative complication rates and outcomes when compared to
      traditional sutures. The use of barbed sutures has been shown to utilize fewer
      resources and may potentially lead to a slight reduction in costs. CONCLUSION:
      Ultimately, no optimal closure technique has been developed, and current studies
      do not provide a clear evidence-based answer. This field needs much more evidence
      based studies before one can draw conclusions. Even though some of these studies
      are prospective and randomized, they may not be generalizable. Also, many of the
      studies have small numbers and are subject to type II errors and fragility.
      Certainly, more studies are needed to truly understand the advantages and
      disadvantages of these new methods. Nevertheless, this review allows orthopedists
      to evaluate the differences between closure methods.

PMID- 29066252
TI  - ABCA1 affects placental function via trophoblast and macrophage.
AB  - AIMS: To study the potential impact of ABCA1 on the function of the placenta.
      MAIN METHODS: Trophoblasts and macrophages were isolated from the placenta with
      enzymatic digestion; Immunofluorescence assay was used to detect the location of
      ABCA1 in cells; RT-PCR and Western-blot were used to detect the expression of
      ABCA1; The cholesterol efflux assays of primary trophoblasts was detected by
      Amplex Red cholesterol assay kit (Invitrogen);Inflammatory factor secretion from
      primary macrophages was detected by Elisa. KEY FINDINGS: ABCA1 was mainly located
      on trophoblast membranes. Decreased ABCA1 expression in trophoblasts reduced the
      cholesterol efflux of trophoblasts (P<0.01). while increased ABCA1 expression in
      trophoblasts reduced the cholesterol efflux of trophoblasts (P<0.05). ABCA1 was
      uniformly expressed on the cell membrane, cytoplasm, and nucleus of macrophages.
      Decreased ABCA1 expression in macrophages, increased inflammatory factors but
      reduced IL-10 (P<0.01). While increased ABCA1 expression in macrophages, reduced
      inflammatory factors but increased IL-10 (P<0.01). SIGNIFICANCE: ABCA1 may be a
      potential target for the prevention of gestation diseases.

PMID- 29066253
TI  - Roselle is cardioprotective in diet-induced obesity rat model with myocardial
      infarction.
AB  - AIMS: Obesity increase the risks of hypertension and myocardial infarction (MI)
      mediated by oxidative stress. This study was undertaken to investigate the
      actions of roselle aqueous extract (R) on cardiotoxicity in obese (OB) rats and
      thereon OB rats subjected to MI. MAIN METHODS: Male Sprague-Dawley rats were fed
      with either normal diet or high-fat diet for 8weeks. Firstly, OB rats were
      divided into (1) OB and (2) OB+R (100mg/kg, p.o, 28days). Then, OB rats were
      subjected to MI (ISO, 85mg/kg, s.c, 2days) and divided into three groups: (1)
      OB+MI, (2) OB+MI+R and (3) OB+MI+enalapril for another 4weeks. KEY FINDINGS:
      Roselle ameliorated OB and OB+MI's cardiac systolic dysfunction and reduced
      cardiac hypertrophy and fibrosis. The increased oxidative markers and decreased
      antioxidant enzymes in OB and OB+MI groups were all attenuated by roselle.
      SIGNIFICANCE: These observations indicate the protective effect of roselle on
      cardiac dysfunction in OB and OB+MI rats, which suggest its potential to be
      developed as a nutraceutical product for obese and obese patients with MI in the
      future.

PMID- 29066254
TI  - Ci8 short, a novel LPS-induced peptide from the ascidian Ciona intestinalis,
      modulates responses of the human immune system.
AB  - The selective modulation of immunity is an emerging concept driven by the vast
      advances in our understanding of this crucial host defense system. Invertebrates
      have raised researchers' interest as potential sources of new bioactive molecules
      owing to their antibacterial, anticancer and immunomodulatory activities. A
      LipoPolySaccharide (LPS) challenge in the ascidian Ciona intestinalis generates
      the transcript, Ci8 short, with cis-regulatory elements in the 3' UTR region that
      are essential for shaping innate immune responses. The derived amino acidic
      sequence in silico analysis showed specific binding to human Major
      Histocompatibility Complex (MHC) Class I and Class II alleles. The role of Ci8
      short peptide was investigated in a more evolved immune system using human
      Peripheral Blood Mononuclear Cells (PBMCs) as in vitro model. The biological
      activities of this molecule include the activation of 70kDa TCR zeta chain
      Associated Protein kinase (ZAP-70) and T Cell Receptor (TCR) Vbeta oligo clonal
      selection on CD4+ T lymphocytes as well as increased proliferation and IFN-gamma
      secretion. Furthermore Ci8 short affects CD4+/CD25high induced regulatory T cells
      (iTreg) subset selection which co-expressed the functional markers TGF
      beta1/Latency Associated Protein (LAP) and CD39/CD73. This paper describes a new
      molecule that modulates important responses of the human adaptive immune system.

PMID- 29066256
TI  - [Treatment outcome, survival and their risk factors among new tuberculosis
      patients co-infected with HIV during the Ebola outbreak in Conakry].
AB  - BACKGROUND: Mortality among TB/HIV co-infected patients remains high in Africa.
      The study aimed to estimate survival and associated factors in a cohort of TB/HIV
      co-infected patients who started tuberculosis treatment during the Ebola outbreak
      in Conakry, Guinea. METHODS: A prospective cohort study was conducted from April
      2014 to December 2015. TB patients with HIV co-infection were enrolled at the
      University Hospital of Conakry. Survival and risk factors were analyzed according
      to Kaplan-Meier's method, log-rank test and Cox's regression. RESULTS: Data from
      573 patients were analyzed. From these, 86 (15.0%) died before the end of
      treatment, 52% occurring within eight weeks of treatment onset. Survival at 4, 12
      and 24 weeks after the beginning of the TB treatment was 92%, 86% and 83%,
      respectively. Independent risk factors associated with death were in the cell CD4
      <200 cells/mm3 [adjusted hazard ratio (AHR): 2.25; 95% CI (confidence intervals):
      1.16-4.37], opportunistic infections other than TB [AHR: 2.89; 95% CI: 1.39
      6.02], and comorbidities [AHR: 4.12; 95% CI: 2.10-8.10]. An increase of one unit
      in hemoglobin [AHR: 0.81; 95% CI: 0.75-0.91] was protective of death. CONCLUSION:
      TB/HIV co-infected patients had a higher fatality rate during treatment of
      tuberculosis. Prevention of opportunistic infections, anemia and proper
      management of tuberculosis treatment in early comorbidities may improve survival
      for TB/HIV co-infected patients in restoring immune function.

PMID- 29066257
TI  - Disparity of end-of-life care in cancer patients with and without schizophrenia:
      A nationwide population-based cohort study.
AB  - BACKGROUND: Cancer patients with schizophrenia may face disparities in end-of
      life care, and it is unclear whether schizophrenia affects their medical care and
      treatment. METHODS: We conducted a nationwide population-based cohort study based
      on the National Health Insurance Research Database of Taiwan. The study
      population included patients >20years old who were newly diagnosed as having one
      of six common cancers between 2000 and 2012 (schizophrenia cohort: 1911 patients
      with both cancer and schizophrenia; non-schizophrenia cohort: 7644 cancer
      patients without schizophrenia). We used a multiple logistic regression model to
      analyze the differences in medical treatment between the two cohorts in the final
      1 and 3months of life. RESULTS: In the 1month before death, there was higher
      intensive care unit utilization in the schizophrenia group [odd ratio (OR)=1.21,
      95% confidence interval (CI)=1.07-1.36] and no significant differences between
      the groups in-hospital stay length or hospice care. The schizophrenia patients
      received less chemotherapy (OR=0.60, 95% CI=0.55-0.66) but more invasive
      interventions, such as cardiopulmonary resuscitation (OR=1.34, 95% CI=1.15-1.57).
      Advanced diagnostic examinations, such as computed tomography/magnetic resonance
      imaging/sonography (OR=0.80, 95% CI=0.71-0.89), were used less often for the
      schizophrenia patients. The 1- and 3-month prior to death results were similar.
      CONCLUSION: End-of-life cancer patients with schizophrenia underwent more
      frequent invasive treatments but less chemotherapy and examinations. Treatment
      plans/advance directives should be discussed with patients/families early to
      enhance end-of-life care quality and reduce health care disparities caused by
      schizophrenia.

PMID- 29066259
TI  - Clinicians should better invest in de-escalation than in fish-oil to prevent
      violence.

PMID- 29066258
TI  - Rates and predictors of relapse following discontinuation of antipsychotic
      medication after a first episode of psychosis.
AB  - BACKGROUND: There is uncertainty about the required duration of long-term
      antipsychotic maintenance medication after a first episode of psychosis. Robust
      predictors of relapse after discontinuation are yet to be identified. The present
      study aimed to determine the proportion of young people who discontinue their
      antipsychotic medication after a first episode of psychosis, the proportion who
      experience relapse, and predictors of relapse. METHODS: A retrospective study of
      all individuals presenting to the Early Psychosis Prevention and Intervention
      Centre between 01/01/11 and 31/12/13 was conducted. A Cox regression analysis was
      conducted to identify predictors of relapse. RESULTS: A total of 544 young people
      with a FEP were included. A trial of discontinuation was undertaken by 61% of the
      cohort. Median duration of antipsychotic medication prior to first trial of
      discontinuation was 174.50days. Amongst those trialing discontinuation, 149
      (45.8%) experienced relapse in a median follow-up time post discontinuation of
      372days. On multivariate analysis, predictors of relapse were a diagnosis of
      cannabis abuse disorder (HR: 1.40), and longer duration of antipsychotic
      medication (HR: 1.05). CONCLUSION: Antipsychotic discontinuation frequently
      occurs earlier than guidelines recommend. Individuals with a diagnosis of
      cannabis abuse are more likely to experience relapse and addressing this
      substance abuse prior to discontinuation could possibly reduce relapse rates.

PMID- 29066260
TI  - Prolactin monitoring in first-episode psychotic patients.

PMID- 29066255
TI  - Comparative analysis of microbial sensing molecules in mucosal tissues with
      aging.
AB  - Host-bacterial interactions at mucosal surfaces require recognition of the
      bacteria by host cells enabling targeted responses to maintain tissue
      homeostasis. It is now well recognized that an array of host-derived pattern
      recognition receptors (PRRs), both cell-bound and soluble, are critical to innate
      immune engagement of microbes via microbial-associated molecular patterns (MAMP).
      This report describes the use of a nonhuman primate model to evaluate changes in
      the expression of these sensing molecules related to aging in healthy gingival
      tissues. Macaca mulatta aged 3-24 years were evaluated clinically and gingival
      tissues obtained, RNA isolated and microarray analysis conducted for gene
      expression of the sensing pattern recognition receptors (PRRs). The results
      demonstrated increased expression of various PRRs in healthy aging gingiva
      including extracellular (CD14, CD209, CLEC4E, TLR4), intracellular (NAIP, IFIH1,
      DAI) and soluble (PTX4, SAA1) PRRs. Selected PRRs were also correlated with both
      bleeding on probing (BOP) and pocket depth (PD) in the animals. These findings
      suggest that aged animals express altered levels of various PRRs that could
      affect the ability of the tissues to interact effectively with the juxtaposed
      microbial ecology, presumably contributing to an enhanced risk of periodontitis
      even in clinically healthy oral mucosal tissues with aging.

PMID- 29066261
TI  - Aberrant corticostriatal connectivity predict positive symptoms of antipsychotic
      naive patients with adolescent-onset schizophrenia during brain maturation.

PMID- 29066263
TI  - Assessing the ecological status of Italian lagoons using a biomass-based index.
AB  - We compared the performance of abundance- and biomass-based M-AMBI in the 13
      major Italian lagoons, using a benthic dataset constituted by 208 sampling sites.
      The relative importance of ecological groups changed when using abundance or
      biomass, sometimes leading to an improved ecological status classification. Being
      biomass more ecologically relevant than abundance, the adoption of a biomass
      based index may better describe the ecological status of lagoons, where the
      community is naturally disturbed and dominated by tolerant and opportunist
      species.

PMID- 29066262
TI  - Distribution characteristics, sources, and ecological risk assessment of
      polycyclic aromatic hydrocarbons in sediments from the Qinhuangdao coastal
      wetland, China.
AB  - Sixteen USEPA priority polycyclic aromatic hydrocarbons (PAHs) were analyzed by
      gas chromatography-mass spectrometry. Twenty-three samples were collected from
      the surface sediments of Qinhuangdao coastal wetlands in this survey. This
      research aimed to identify the PAHs contamination level, composition pattern,
      pollution sources, and assess the ecological risk of PAHs. The results showed
      that the sum of PAH concentrations ranged from 341.61ng/g to 4703.80ng/g (mean:
      1367.80ng/g), which is higher than the reported values for different wetlands
      worldwide. Five- and four-ring PAHs (34.08% and 32.97% of ?16PAHs, severally)
      were predominant in the wetland sediment. The PAH source distribution in the
      surface sediments was determined using diagnostic ratio and PCA/MLR.
      Consequently, multiple PAH sources were found. Of the total PAHs, 70.01% was
      derived from vehicular emission, 25.73% from coke oven, and 4.26% from petroleum
      based product spills. The effect range low/effect range median (ERL/ERM) values
      indicated a low toxicity risk level. However, the DBahA concentrations exceeded
      the ERL level, and even the ERM level, in some stations. The mean effects range
      median quotient (M-ERM-Q) suggests a low ecological risk for the PAHs, but a
      medium risk for some stations in the coastal wetland sediments.

PMID- 29066264
TI  - A pilot study on corneal Langerhans cells in keratoconus.
AB  - PURPOSE: To report the density and morphology of cells that are analogous to
      corneal Langerhans cells and their associations in keratoconus. MATERIALS AND
      METHODS: This prospective cross-sectional study included a convenience sample of
      keratoconus subjects aged between 18-65 years. Corneal topography, assessment of
      ocular symptoms, tear variables, corneal sensitivity, in-vivo confocal microscopy
      were performed. The number of Langerhans cells were manually counted and averaged
      across three central corneal images. Cell morphology was graded on a 0-3 scale,
      where grade 3 indicates cells with long visible dendrites. Associations of
      Langerhans cells with other variables were evaluated using Spearman's
      correlation. RESULTS: Twenty-one keratoconus subjects with a mean age of 43+/-11
      years were included. Eighty-one percent of them were males, 48% had mild
      keratoconus and 52% were contact lens wearers. Langerhans cells were present in
      the central cornea in 91% of subjects. Median cell density was 15 cells/mm2(IQR:
      3-21). Cell morphology of grades 2 or 3 (with short or long dendrites) was seen
      in 71% of subjects. There was a significant association between Langerhans cell
      frequency and density with male gender (rho and p-values: -0.669, 0.001 and 
      0.441,0.045) and between Langerhans cell density and nerve fibre tortuosity
      (0.479,0.028). No significant association observed with age, contact lens wear or
      ocular symptoms. CONCLUSION: Langerhans cells were present in a significant
      number of subjects suggesting the possibility of inflammation in keratoconus.
      Based on the association of Langerhans cells with nerve parameters, we propose
      inflammation as the underlying cause for corneal nerve changes in keratoconus.

PMID- 29066266
TI  - Cross Pin Versus Interference Screw for Femoral Graft Fixation in Hamstring
      Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis
      of Clinical Outcomes.
AB  - PURPOSE: To compare the effectiveness of a cross pin and interference screw for
      femoral graft fixation in primary anterior cruciate ligament reconstruction
      (ACLR) and provide an appropriate reference for orthopaedic surgeons. METHODS:
      The Medline, Cochrane Library, Web of Science, Scopus, and PubMed databases were
      searched in March 2016, and comparative trials using cross-pin and interference
      screw devices for femoral graft fixation in primary hamstring ACLR with clinical
      outcome measurements were included in the review. Trials with no controlled
      groups, hybrid fixation, no clinical outcomes, or follow-up of less than 1 year
      were excluded. The quality of the included studies was assessed with the Cochrane
      Back Review Group 12-item scale. Abstracted data were pooled with fixed or random
      effects depending on the detected heterogeneity. The outcome measures were the
      scoring system and physical examination findings, including the Lysholm score,
      International Knee Documentation Committee score or grade, Tegner score, negative
      Lachman test, negative pivot-shift test, and instrumented side-to-side anterior
      posterior laxity difference. RESULTS: All the studies reviewed were of
      prospective design. Within the cross-pin group, patients who underwent hamstring
      ACLR showed a significantly smaller instrumented side-to-side anterior-posterior
      laxity difference when compared with interference screw fixation (weighted mean
      difference, 0.38 mm [95% confidence interval, 0.08-0.67 mm]; P = .01), whereas
      the results of a negative Lachman test and negative pivot-shift test were
      comparable. Outcomes regarding the scoring system did not reach a significant
      difference between the 2 groups. CONCLUSIONS: The statistically decreased
      instrumented side-to-side anterior-posterior laxity difference achieved by cross
      pin transfixation appears to be of limited clinical significance when compared
      with interference screw fixation in primary hamstring ACLR. Clinically, the
      performance of cross-pin devices did not show a significant advantage over that
      of the interference screw for femoral graft fixation in hamstring ACLR. LEVEL OF
      EVIDENCE: Level II.

PMID- 29066265
TI  - Long-term safety, tolerability, and efficacy of evolocumab in patients with
      heterozygous familial hypercholesterolemia.
AB  - BACKGROUND: Evolocumab, a fully human monoclonal antibody against proprotein
      convertase subtilisin/kexin type 9, is safe and effective when dosed biweekly
      (Q2W) or monthly (QM) in patients with heterozygous familial hypercholesterolemia
      (HeFH) as demonstrated in two 12-week trials: Reduction of LDL-C With PCSK9
      Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD;
      phase 2) and RUTHERFORD-2 (phase 3). OBJECTIVE: The objective of the study was to
      evaluate long-term efficacy, safety, and tolerability of evolocumab during open
      label extension trials. METHODS: Patients completing parent trials were re
      randomized 2:1 to evolocumab plus standard of care (SOC) or SOC alone for 52
      weeks (Open-Label Study of Long-term Evaluation Against LDL-C [OSLER-1]) or 48
      weeks (OSLER-2). Evolocumab dosing was 420 mg QM (OSLER-1) and 140 mg Q2W or 420
      mg QM (OSLER-2). A pooled analysis of OSLER data was performed from this subset
      of HeFH patients. RESULTS: Four hundred forty HeFH patients from RUTHERFORD (n =
      147) and RUTHERFORD-2 (n = 293) (mean [standard deviation] age 51 [12] years, 58%
      male, 90% White) were randomized to evolocumab plus SOC (n = 289) or SOC (n =
      151). The 48-week period was completed by 425 patients (96.6%). Eight patients
      discontinued evolocumab plus SOC (2.8%) and 7 discontinued SOC (4.6%). Compared
      to parent study baseline, patients receiving evolocumab plus SOC experienced a
      mean 53.6% reduction in low-density lipoprotein cholesterol after 48 weeks. No
      patient experienced an adverse event leading to permanent evolocumab
      discontinuation during the 1-year SOC-controlled period. Serious adverse event
      rates were similar between groups (evolocumab plus SOC, 7.3%; SOC, 8.6%).
      CONCLUSION: Continued use of evolocumab added to SOC in patients with HeFH yields
      persistent and marked low-density lipoprotein cholesterol reductions during 48
      weeks of follow-up. Long-term dosing of evolocumab with SOC was safe and well
      tolerated.

PMID- 29066267
TI  - Accuracy and Reliability of a Simple Calculation for Measuring Glenoid Bone Loss
      on 3-Dimensional Computed Tomography Scans.
AB  - PURPOSE: To establish the accuracy and reliability of the circle-line method
      (CLM) of measuring glenoid bone loss; to compare the CLM calculation with a
      traditionally used method of calculating a ratio; and to evaluate surgeons'
      ability to estimate the amount of glenoid bone loss before performing any
      calculations. METHODS: Three-dimensional reconstructions of computed tomography
      scans of consecutive patients with anterior instability and glenoid bone loss
      were reviewed by 13 surgeons blinded to the diagnosis. The reviewers made
      estimations of bone loss before creating any measurements by viewing the
      available computed tomography scan as well as the 3-dimensional reconstructions.
      They selected an en face view of the glenoid to create a best-fit circle. Bone
      loss calculation with a traditional linear method as well as a CLM calculated by
      algebraic geometry was completed. The CLM requires calculation of the diameter of
      a best-fit circle on the glenoid, as well as the length of a single line along
      the circle representing the line of bone loss. All methods were compared with a
      computerized method of tracing the area of the glenoid within a best-fit circle.
      Interobserver and intraobserver calculations were performed. Analysis-of-variance
      testing was used to compare the estimates of bone loss versus the CLM-calculated
      bone loss. Tukey post hoc analysis was used to define the accuracy of the CLM
      calculation compared with a more traditional method of calculating bone loss.
      RESULTS: Bone loss estimations were significantly different from CLM-calculated
      bone loss in all cases except those with greater than 25% bone loss. The CLM was
      more accurate in all types of bone loss except cases of greater than 25% bone
      loss. Interobserver reliability was very good for the glenoid diameter
      measurement and moderate for the CLM. Intraobserver reliability ranged from
      moderate to good for all methods of measurement. CONCLUSIONS: Surgeon estimations
      of glenoid bone loss, as well as traditional line-measurement calculations, are
      inconsistent and unreliable for accurate determination of the optimal surgical
      treatment for anterior shoulder instability. The CLM is a simple, reproducible,
      and accurate method for determining glenoid bone loss and does not require
      specialized software or imaging protocols. LEVEL OF EVIDENCE: Level II,
      diagnostic study.

PMID- 29066268
TI  - Do Skin Lacerations Imply Tissue Transfer From Surgeon to Patient During
      Arthroscopic Knot Tying?
AB  - PURPOSE: To use simulated arthroscopic knot tying to assess (1) whether
      epithelial cells from the surgeon's hands were transmitted to the suture and (2)
      whether the number of knots tied or the presence of glove tears would correlate
      with the number of cells transmitted. METHODS: Knots were tied in a simulated
      arthroscopic environment using a nonabsorbable No. 2 suture over a metal hook.
      The surgeon was double gloved for each knot tied. For each "anchor," a surgeon's
      knot was tied, followed by 3 reversed half-hitches on alternating posts. Multiple
      skin lacerations were sustained by the surgeon during each knot-tying session.
      Gloves were collected after tying 2, 4, or 6 anchors. Gloves were tested for
      perforation by (1) electroconductivity and (2) saline solution load testing.
      Cytopathologic ThinPrep analysis was applied and allowed for the number of
      epithelial cells found on each suture (within 10 high-powered fields) to be
      counted. Statistical analysis included analysis of variance and logistic
      regression. RESULTS: There was no significant difference in the number of
      epithelial cells identified in any of the groups compared with the negative
      control groups (P > .05) or with each other (P > .05). Glove tears were present
      in 3.3% of gloves (50% in inner and 50% in outer gloves) and 1.7% of gloves (50%
      in inner and 50% in outer gloves) by electroconductivity and saline solution load
      testing, respectively. There was no significant association between glove tears
      and the number of epithelial cells found on the suture (P > .05). CONCLUSIONS:
      Epithelial cells were transmitted to the suture during simulated arthroscopic
      knot tying. However, despite multiple skin lacerations produced during knot-tying
      sessions, the number of cells transmitted was not significantly different when
      compared with the negative controls. The number of cells transmitted did not
      correlate with the number of knots tied and/or the presence of glove tears.
      CLINICAL RELEVANCE: Skin lacerations on the surgeon's fingers are often noted
      after arthroscopic knot tying. However, despite these skin lacerations, no skin
      tissue is transferred across the surgical gloves to the suture itself.

PMID- 29066269
TI  - Contact Versus Noncontact Anterior Cruciate Ligament Injuries: Is Mechanism of
      Injury Predictive of Concomitant Knee Pathology?
AB  - PURPOSE: To determine if mechanism of injury is predictive of concomitant knee
      pathology found at the time of anterior cruciate ligament (ACL) reconstruction.
      METHODS: All patients aged 16 to 35 who underwent ACL reconstruction at our
      institution between January 2009 and December 2015 were retrospectively reviewed.
      Mechanism of injury was determined from patient history. The presence of meniscal
      or chondral damage was determined from operative records, while collateral
      ligament injuries were determined by the treating surgeon's diagnosis after
      physical examination and their review of magnetic resonance imaging findings.
      Patients with inadequate documentation, history of a subsequent instability
      episode following the initial injury, or prior history of knee pathology were
      excluded. RESULTS: Six hundred eighty-seven patients (169 contact and 518
      noncontact) were included. A 2-fold increase in the incidence of collateral
      ligament injury was identified between the 2 groups with 114 (67.5%) in the
      contact group and 175 (33.8%) in the noncontact group (P < .001). Twenty-six
      patients (15.4%) in the contact group compared with 9 (1.7%) in the noncontact
      group had a grade III collateral ligament injury (P < .001). Chondral injury was
      identified in 41 (24.3%) patients in the contact group and 87 (16.8%) in the
      noncontact group (P = .05) with 9 (5.3%) grade IV lesions in the contact group
      and 4 (0.8%) in the noncontact group (P < .001). Eleven patients in the contact
      group (6.5%) and 15 in the noncontact group (2.9%) had a chondral injury to the
      lateral femoral condyle (P = .04). CONCLUSIONS: Although we found no difference
      in the incidence or type of meniscal tears, we found a significant increase in
      the incidence of grade IV chondral injury, chondral injury to the lateral femoral
      condyle, and grade III collateral ligament damage in the setting of contact ACL
      injuries. This knowledge can aid surgeons in preoperative planning and patient
      counseling. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 29066270
TI  - Aquagenic pruritus in polycythemia vera: a cross-sectional study.

PMID- 29066272
TI  - The art of being in 2 rooms at 1 time: Ethical issues with overlapping surgery.

PMID- 29066271
TI  - Effect of secukinumab on quality of life and psoriasis-related symptoms: A
      comparative analysis versus ustekinumab from the CLEAR 52-week study.
AB  - BACKGROUND: Secukinumab has demonstrated greater sustained skin clearance than
      ustekinumab through week 52, greater improvement in symptoms and health-related
      quality of life, and comparable safety profile. OBJECTIVE: To assess the impact
      of secukinumab versus that of ustekinumab on complete relief from psoriasis
      related symptoms, time to response in terms of health-related quality of life,
      and cumulative benefit among patients with moderate-to-severe plaque psoriasis.
      METHODS: Psoriasis-related pain, itching, and scaling and the Dermatology Life
      Quality Index (DLQI) score were compared between treatments on the basis of time
      to complete relief of symptoms and time to DLQI response in the CLEAR trial.
      Cumulative benefit over 52 weeks based on Psoriasis Area and Severity Index
      score, symptom relief, and DLQI response were evaluated by area under the curve
      analysis. RESULTS: Significantly more patients treated with secukinumab achieved
      complete relief of pain at weeks 16 and 52 (all P < .05). Complete relief of
      itching and scaling occurred significantly faster with secukinumab (median, 4
      weeks faster for itching and 8 weeks faster for scaling [P < .001]). Response as
      measured by the DLQI was 4 weeks faster with secukinumab (P < .0001). Cumulative
      benefits were greater with secukinumab (all P < .05). LIMITATIONS: Analyses were
      post hoc. CONCLUSION: This patient-reported outcome analysis confirms greater and
      sustained benefits of secukinumab versus those of ustekinumab treatment on
      patients' lives.

PMID- 29066273
TI  - Cutaneous dermatomyositis disease course followed over time using the Cutaneous
      Dermatomyositis Disease Area and Severity Index.
AB  - BACKGROUND: Limited studies describe the longitudinal course of cutaneous
      dermatomyositis (DM). OBJECTIVE: To characterize disease course in treated
      cutaneous DM by using the Cutaneous Dermatomyositis Disease Area and Severity
      Index (CDASI), a validated outcome instrument. METHODS: A retrospective cohort
      included patients with DM who had their CDASI activity subscore recorded for at
      least 2 years. Disease progression was classified as improved, worsened, or
      stable, and disease course was classified as monophasic, polyphasic, or chronic.
      Subjects were divided into groups with disease of mild (n = 16) and moderate-to
      severe (n = 24) baseline severity. RESULTS: A total of 40 patients with DM met
      inclusion criteria. The majority demonstrated improvement in disease activity (n
      = 21 [52.5%]) rather than worsening (n = 7 [17.5%]) and stable (n = 12 [30.0%])
      disease. Most patients with mild disease remained stable (n = 10 [62.5%]),
      whereas most with moderate-to-severe disease improved (n = 19 [79.2%]). A
      polyphasic course (n = 33 [82.5%]) predominated over monophasic (n = 5 [12.5%])
      and chronic (n = 2 [5%]) courses. The average number of flares per year per
      number of years of follow-up was independent of baseline disease activity.
      LIMITATIONS: The retrospective design, potential referral bias, and cutoff values
      in classification criteria are limitations. CONCLUSION: Baseline CDASI activity
      score is associated with particular patterns of disease course and progression in
      cutaneous DM.

PMID- 29066274
TI  - Self-healing juvenile cutaneous mucinosis: Clinical and histopathologic findings
      of 9 patients: The relevance of long-term follow-up.
AB  - BACKGROUND: Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder,
      and its pathogenesis and long-term prognosis are unknown. OBJECTIVE: To elucidate
      the clinical and histopathologic characteristics, pathogenesis, and outcome in
      patients with SHJCM. METHODS: Retrospective study of 9 patients with SHCJM. To
      complement initial findings, data collection forms were sent to the referring
      physicians. RESULTS: All patients had an acute onset of firm nodules. Of the 9
      patients, 6 presented initially with waxy papules on the dorsum of the hands; 5
      suffered from periorbital edema, and 6 had a febrile prodrome. Histopathologic
      assessment of the papules revealed dermal mucin deposition, whereas the nodules
      showed proliferative fasciitis-like features or nonspecific chronic lobular
      panniculitis. Laboratory studies elicited evidence of active viral infection in 2
      patients (human herpes virus 6 and rotavirus). Seven cases had spontaneous
      resolution within 6 months, and 2 patients with incomplete resolution showed
      subsequent transition to fibroblastic rheumatism and an autoinflammatory
      rheumatologic disease, respectively. LIMITATIONS: This was a retrospective study
      with incomplete data from referring physicians. CONCLUSIONS: Although spontaneous
      complete regression is expected, patients with SHJCM need long-term follow-up
      because of the possible development of dematorheumatolgic conditions. The
      pathogenetic role of microbial agents deserves further investigation.

PMID- 29066275
TI  - The spectrum of manifestations in desmoplakin gene (DSP) spectrin repeat 6 domain
      mutations: Immunophenotyping and response to ustekinumab.
AB  - BACKGROUND: The immune abnormalities underlying the ichthyoses are poorly
      understood. OBJECTIVE: To determine the immunophenotype of an ichthyosis
      resulting from mutations in the spectrin repeat 6 (SR6) domain of desmoplakin
      gene (DSP) and target therapy on the basis of molecular pathogenesis. METHODS:
      Immunophenotyping was performed by using the blood and skin of a girl with SR6
      region DSP mutations causing erythroderma/ichthyosis and cardiomyopathy. RESULTS:
      On the basis of the discovery of T helper 1 and T helper 17/interleukin 23
      skewing in the skin and T helper 17/interleukin 22 skewing in blood, ustekinumab
      therapy was initiated. Ustekinumab was also administered to a boy with an SR6
      region DSP mutation and ichthyosis without cardiomyopathy. Both children
      responded despite previous poor responses to immunosuppressants and retinoids.
      LIMITATIONS: Small number of patients and immunophenotyping in only 1 patient.
      CONCLUSION: An understanding of the molecular basis of inflammation in rare
      cutaneous disorders can lead to targeted therapy, which promises to be more
      beneficial than broad immunosuppressants.

PMID- 29066278
TI  - Structural aspects of protein kinase ASK1 regulation.
AB  - Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of
      the mitogen-activated protein kinase kinase kinase (MAP3K) family, activates the
      p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase (JNK)
      signaling cascades in response to various stressors. ASK1 activity is tightly
      regulated through phosphorylation and interaction with various binding partners.
      However, the mechanistic details underlying the ASK1 regulation are still not
      fully understood. This review focuses on recent advances in structural studies of
      protein kinase ASK1 and on the insights they provide into its mechanism of
      regulation. In addition, we also discuss protein-protein interactions between
      ASK1 and its binding partners thioredoxin (TRX) and 14-3-3 protein.

PMID- 29066277
TI  - Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated
      mitogen-activated protein kinase kinase kinase (MAP3K) family. ASK1 is an
      attractive drug target, owing to its essential role in a wide variety of human
      diseases including neurodegenerative disorders, inflammatory diseases and cancer.
      Recent studies have suggested that pharmacological manipulations using small
      molecule ASK1 inhibitors may be beneficial in experimental human disease models.
      In this review, we highlight the current understanding of ASK1 inhibitors as a
      potential therapy for human diseases.

PMID- 29066276
TI  - Signaling by cell surface death receptors: Alterations in head and neck cancer.
AB  - Cell surface death receptors are members of the tumor necrosis factor receptor
      (TNFR) superfamily and mediate signals leading to the induction of apoptosis or
      necroptosis, as well as NF-kappaB-mediated cell survival. These biochemical
      processes play key roles in cell growth, development, tissue homeostasis, and
      immune responses. The downstream signaling complexes activated by different death
      receptors can differ significantly and are subject to multiple, distinct
      regulatory mechanisms. Dysregulation of signaling by the TNFR superfamily
      contributes to a variety of pathologic conditions, including defective immune
      responses and cancer. Caspase-8 signaling is important for mediating death
      receptor signals leading to either apoptosis or NF-kappaB activation. By
      contrast, inactivation of caspase-8 or loss of caspase-8 expression shifts death
      receptor signaling to the necroptosis pathway. Notably, the gene encoding caspase
      8 is mutated in roughly ten percent of head and neck cancers. These findings
      support the hypothesis that alterations in the biochemical pathways mediated by
      death receptors have important consequences for the development of head and neck,
      and possibly other, cancers.

PMID- 29066280
TI  - Implantation and testing of a novel episcleral pressure transducer: A new
      approach to telemetric intraocular pressure monitoring.
AB  - Measurement of intraocular pressure (IOP) is an essential tool in monitoring
      glaucoma. Single IOP assessments during clinical routine examinations represent
      punctual values and are not able to identify IOP fluctuations and spikes.
      Telemetric IOP measurements are able to monitor IOP during the day and night, and
      are location-independent. Six telemetric episcleral IOP sensors were investigated
      after minimally invasive subconjunctival implantation in 6 eyes of 6 New-Zealand
      White rabbits. Three of the 4 edges of the implant were fixated intrasclerally
      with non-absorbable sutures. The sutures were stitched into the edges of the
      implants' silicone rubber encasements. Telemetric IOP measurements were validated
      1 week, 4 weeks, 8 weeks, 12 weeks and 30 weeks after implantation. For each
      validation the anterior chamber was cannulated and connected to a height
      adjustable water column. Different intracameral pressure levels (10-45 mmHg) were
      generated by height adjustment of the water column. Measurement reliability and
      concordance between telemetric and intracameral IOP was validated using Bland
      Altman analysis. Overall comparison (10-45 mmHg) between telemetric and
      intracameral pressure revealed a standard deviation of +/-1.0 mmHg. A comparison
      of pressure values in the range between 10 and 30 mmHg revealed a standard
      deviation of +/-0.8 mmHg. Device deficiency was related to follow-up length: 4
      weeks after implantation, 3 of the 6 sensors showed malfunction, with all sensors
      having failed 30 weeks after implantation. The most likely reason for the sensor
      malfunction is the loss of hermeticity as a result of penetration of the
      encasement during the episcleral fixation, resulting from the lack of preformed
      suture holes at the implants encasement. However, no clinical signs of injury or
      inflammation of the conjunctiva, sclera, implantation site or any other involved
      structures were observed, except for an expected mild short-term irritation
      postoperatively. The episcleral pressure transducer for telemetric IOP monitoring
      is able to assess IOP without the need for invasive intraocular surgery.
      Episcleral implantation is an easy and safe procedure and can be undone very
      easily, so even temporary implantation and IOP measurements could be possible in
      the future. Sensor malfunction over time is a problem that needs to be addressed.
      Improvements in sensor encapsulation and especially preformed suture holes could
      significantly decrease the failure rate and increase durability.

PMID- 29066279
TI  - Formulation of 3D Printed Tablet for Rapid Drug Release by Fused Deposition
      Modeling: Screening Polymers for Drug Release, Drug-Polymer Miscibility and
      Printability.
AB  - The primary aim of this study was to identify pharmaceutically acceptable
      amorphous polymers for producing 3D printed tablets of a model drug, haloperidol,
      for rapid release by fused deposition modeling. Filaments for 3D printing were
      prepared by hot melt extrusion at 150 degrees C with 10% and 20% w/w of
      haloperidol using Kollidon(r) VA64, Kollicoat(r) IR, AffinsiolTM15 cP, and HPMCAS
      either individually or as binary blends (Kollidon(r) VA64 + AffinisolTM 15 cP,
      1:1; Kollidon(r) VA64 + HPMCAS, 1:1). Dissolution of crushed extrudates was
      studied at pH 2 and 6.8, and formulations demonstrating rapid dissolution rates
      were then analyzed for drug-polymer, polymer-polymer and drug-polymer-polymer
      miscibility by film casting. Polymer-polymer (1:1) and drug-polymer-polymer
      (1:5:5 and 2:5:5) mixtures were found to be miscible. Tablets with 100% and 60%
      infill were printed using MakerBot printer at 210 degrees C, and dissolution
      tests of tablets were conducted at pH 2 and 6.8. Extruded filaments of
      Kollidon(r) VA64-AffinisolTM 15 cP mixtures were flexible and had optimum
      mechanical strength for 3D printing. Tablets containing 10% drug with 60% and
      100% infill showed complete drug release at pH 2 in 45 and 120 min, respectively.
      Relatively high dissolution rates were also observed at pH 6.8. The 1:1-mixture
      of Kollidon(r) VA64 and AffinisolTM15 cP was thus identified as a suitable
      polymer system for 3D printing and rapid drug release.

PMID- 29066281
TI  - Visualizing melanosomes, lipofuscin, and melanolipofuscin in human retinal
      pigment epithelium using serial block face scanning electron microscopy.
AB  - To assess serial section block-face scanning electron microscopy (SBFSEM) for
      retinal pigment epithelium (RPE) ultrastructure, we determined the number and
      distribution within RPE cell bodies of melanosomes (M), lipofuscin (L), and
      melanolipofuscin (ML). Eyes of 4 Caucasian donors (16M, 32F, 76F, 84M) with
      unremarkable maculas were sectioned and imaged using an SEM fitted with an in
      chamber automated ultramicrotome. Aligned image stacks were generated by
      alternately imaging an epoxy resin block face using backscattered electrons, then
      removing a 125 nm-thick layer. Series of 249-499 sections containing 5-24 nuclei
      were examined per eye. Trained readers manually assigned boundaries of individual
      cells and x,y,z locations of M, L, and ML. A Density Recovery Profile was
      computed in three dimensions for M, L, and ML. The number of granules per RPE
      cell body in 16M, 32F, 76F, and 84M eyes, respectively, was 465 +/- 127 (mean +/-
      SD), 305 +/- 92, 79 +/- 40, and 333 +/- 134 for L; 13 +/- 9; 6 +/- 7, 131 +/- 55,
      and 184 +/- 66 for ML; and 29 +/- 19, 24 +/- 12, 12 +/- 7, and 7 +/- 3 for M.
      Granule types were spatially organized, with M near apical processes. The
      effective radius, a sphere of decreased probability for granule occurrence, was 1
      MUm for L, ML, and M combined. In conclusion, SBFEM reveals that adult human RPE
      has hundreds of L, LF, and M and that granule spacing is regulated by granule
      size alone. When obtained for a larger sample, this information will enable
      hypothesis testing about organelle turnover and regulation in health, aging, and
      disease, and elucidate how RPE-specific signals are generated in clinical optical
      coherence tomography and autofluorescence imaging.

PMID- 29066282
TI  - Raman spectroscopy predicts the link between claw keratin and bone collagen
      structure in a rodent model of oestrogen deficiency.
AB  - Osteoporosis is a common disease characterised by reduced bone mass and an
      increased risk of fragility fractures. Low bone mineral density is known to
      significantly increase the risk of osteoporotic fractures, however, the majority
      of non-traumatic fractures occur in individuals with a bone mineral density too
      high to be classified as osteoporotic. Therefore, there is an urgent need to
      investigate aspects of bone health, other than bone mass, that can predict the
      risk of fracture. Here, we successfully predicted association between bone
      collagen and nail keratin in relation to bone loss due to oestrogen deficiency
      using Raman spectroscopy. Raman signal signature successfully discriminated
      between ovariectomised rats and their sham controls with a high degree of
      accuracy for the bone (sensitivity 89%, specificity 91%) and claw tissue
      (sensitivity 89%, specificity 82%). When tested in an independent set of claw
      samples the classifier gave 92% sensitivity and 85% specificity. Comparison of
      the spectral changes occurring in the bone tissue with the changes occurring in
      the keratin showed a number of common features that could be attributed to common
      changes in the structure of bone collagen and claw keratin. This study
      established that systemic oestrogen deficiency mediates parallel structural
      changes in both the claw (primarily keratin) and bone proteins (primarily
      collagen). This strengthens the hypothesis that nail keratin can act as a
      surrogate marker of bone protein status where systemic processes induce changes.

PMID- 29066283
TI  - The extent of pyroptosis varies in different stages of apical periodontitis.
AB  - Apical periodontitis (AP) is an inflammation affecting the periapical region of
      tooth root. Microbial pathogens activate inflammasomes and promote the production
      of pro-inflammatory cytokines. Caspase-1-mediated pyroptosis is a possible
      mechanism involved in the initiation and progression of AP. The purpose of this
      study was to evaluate the role of caspase-1 and pyroptosis on AP at different
      stages. Human periapical inflammatory tissue was collected to study chronic AP
      stage. Human periodontal ligament fibroblasts (hPDLFs) were stimulated with
      lipopolysaccharide in vitro for 24h to simulate early AP stage. Experimental AP
      rat model was established to study acute AP stage from 0d to 28d. The results
      showed that NLRP3, cleaved caspase-1 and Interleukin (IL)-1beta were enhanced in
      all AP stages. Caspase-1 activation was detectable in most cells. However, the
      level of pyroptosis was in accordance with the degree of AP inflammation. Early
      and chronic AP showed a comparable hemostasis state, with pyroptosis remaining in
      a reduced level. On the contrary, extensive pyroptosis accelerated inflammation
      and induced cell death in acute AP. VX765, a caspase-1 inhibitor, was used in an
      experimental AP rat model. The results showed that VX765 suppressed bone loss,
      suggesting a role of pyroptosis on bone resorption in acute AP. VX765 also
      inhibited the expressions of IL-1beta, Monocyte chemoattractant protein-1 (MCP
      1), IL-6 and IL-8 in vitro, thus decreased inflammatory responses during AP. In
      conclusion, caspase-1 and pyroptosis contributed to AP inflammation and lesion
      and pyroptosis extent was in line with AP progression.

PMID- 29066285
TI  - Understanding vitamin D metabolism in pregnancy: From physiology to
      pathophysiology and clinical outcomes.
AB  - This critical time frame of intrauterine life development is considered of major
      importance on the metabolic imprinting of overall health of the offspring, in
      later life. This requires a delicate immune balance that nurtures the allogeneic
      fetus, while maintaining reactivity against pathogens. Dysregulation of these
      tightly controlled biophenomena at a systemic and placental level, have been
      considered as a potential mechanism mediating pathogenesis of preeclampsia and
      spontaneous birth. In this context, vitamin D has been considered as a
      significant regulator of both innate and adaptive immunity by regulating cell
      proliferation, differentiation and apoptosis. Vitamin D metabolism during
      pregnancy manifests striking differences as compared to the non-pregnant state.
      Calcitriol is increasing >2-3 fold in the first weeks of pregnancy whereas
      maternal 25-hydroxyvitamin D crosses the placental barrier and represents the
      main pool of vitamin D in the fetus. Moreover, during pregnancy, vitamin D
      receptor and regulatory metabolic enzymes are expressed in the placenta and
      decidua, indicating a potential critical point in the immunomodulation at the
      maternal-fetal interface. Considering these effects, maternal hypovitaminosis D
      during pregnancy has been associated with pregnancy related disorders. This
      review focuses on the mechanistic basis of these adaptive changes, as a
      background for the development of pregnancy related disorders, with a discourse
      on the pathophysiology relating hypovitaminosis D and clinical outcomes.

PMID- 29066286
TI  - Cryptosporidium and Giardia safety margin increase in leafy green vegetables
      irrigated with treated wastewater.
AB  - The presence of Cryptosporidium and Giardia in waste water is a main concern
      because water reuse for irrigation can jeopardize human health. Spanish
      Legislation for water reuse does not oblige to analyze the presence of both
      pathogens Cryptosporidium and Giardia in reused water for irrigation. Therefore,
      the objective of this paper is to determine the influence of wastewater treatment
      in the increase of the consumer safety margin in relation to the presence of
      Cryptosporidium and Giardia in leafy green vegetables. With this aim in mind, a
      total of 108 samples from raw (influent) and treated wastewater (effluent) from
      three wastewater treatment plants in Spain were analysed according to USEPA
      Method 1623. Effluent results show that Cryptosporidium oocysts average counts
      ranged from 1.38 to 2.6/L oocysts and Giardia cysts ranged from 0.6 to 1.7/L
      cysts, which means a removal values of 2.7 log, 2.5 log and 1.8 log for
      Cryptosporidium oocysts and 1 log, 2 log and 2.2 log for Giardia cysts in the
      three wastewater treatment plants analysed. In relation to safety margin the
      highest probability that exposure exceed the dose response was observed for
      Giardia. In addition, the sensitivity analysis showed that (oo)cysts
      concentration present in the leafy green vegetables and the human dose-response
      were the most influential inputs in the safety margin obtained.

PMID- 29066284
TI  - Amylin and diabetic cardiomyopathy - amylin-induced sarcolemmal Ca2+ leak is
      independent of diabetic remodeling of myocardium.
AB  - Amylin is a pancreatic beta-cell hormone co-secreted with insulin, plays a role
      in normal glucose homeostasis, and forms amyloid in the pancreatic islets of
      individuals with type-2 diabetes. Aggregated amylin is also found in blood and
      extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is
      associated with myocyte Ca2+ dysregulation in diabetic rats expressing human
      amylin. Whether deposition of amylin in the heart is a consequence of or a
      contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout
      (AKO) mice intravenously infused with either human amylin (i.e, the aggregated
      form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the hypothesis
      that aggregated amylin accumulates in the heart in the absence of diabetes. AKO
      mice infused with human amylin, but not rodent amylin, showed amylin deposits in
      the myocardium. Cardiac amylin level was larger in males compared to females.
      Sarcolemmal Ca2+ leak and Ca2+ transients were increased in myocytes isolated
      from males infused with human amylin while no significant changes occurred in
      either females injected with human amylin or in rat amylin-infused mice. In
      isolated cardiac myocytes, the amylin receptor antagonist AC-187 did not
      effectively block the interaction of amylin with the sarcolemma. In conclusion,
      circulating aggregated amylin accumulates preferentially in male vs. female
      hearts and its effects on myocyte Ca2+ cycling do not require diabetic remodeling
      of the myocardium. This article is part of a Special issue entitled Cardiac
      adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan
      F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.

PMID- 29066287
TI  - Multiple identification of most important waterborne protozoa in surface water
      used for irrigation purposes by 18S rRNA amplicon-based metagenomics.
AB  - Understanding waterborne protozoan parasites (WPPs) diversity has important
      implications in public health. In this study, we evaluated a NGS-based method as
      a detection approach to identify simultaneously most important WPPs using 18S
      rRNA high-throughput sequencing. A set of primers to target the V4 18S rRNA
      region of WPPs such as Cryptosporidium spp., Giardia sp., Blastocystis sp.,
      Entamoeba spp, Toxoplasma sp. and free-living amoebae (FLA) was designed. In
      order to optimize PCR conditions before sequencing, both a mock community with a
      defined composition of representative WPPs and a real water sample inoculated
      with specific WPPs DNA were prepared. Using the method proposed in this study, we
      have detected the presence of Giardia intestinalis, Acanthamoeba castellanii,
      Toxoplasma gondii, Entamoeba histolytica and Blastocystis sp. at species level in
      real irrigation water samples. Our results showed that untreated surface
      irrigation water in open fields can provide an important source of WPPs.
      Therefore, the methodology proposed in this study can establish a basis for an
      accurate and effective diagnostic of WPPs to provide a better understanding of
      the risk associated to irrigation water.

PMID- 29066288
TI  - Molecular phylogenetics of dinophytes harboring diatoms as endosymbionts
      (Kryptoperidiniaceae, Peridiniales), with evolutionary interpretations and a
      focus on the identity of Durinskia oculata from Prague.
AB  - Peridinialean dinophytes include a unique evolutionary group of algae harboring a
      diatom as an endosymbiont (Kryptoperidiniaceae), whose phylogenetic origin and
      internal relationships are not fully resolved at present. Several interpretations
      of the thecal plate pattern present in Durinskia oculata currently compete and
      lead to considerable taxonomic confusion. Moreover, it is unclear at present
      whether the species is restricted to freshwater habitats, or occurs in the marine
      environment as well. We collected material at the type locality of D. oculata in
      the Czech Republic and established monoclonal strains. Dinophyte cells were
      studied using light and electron microscopy, and we also determined DNA sequences
      of several rRNA regions (including the Internal Transcribed Spacers) for
      molecular characterization and phylogenetics. The morphology of strain GeoM*662
      indicated a plate formula of Po, X, 4', 2a, 6", 5c, 5s, 5''', 2'''', which was
      sustained also in form of a microscopic slide serving as an epitype. In the
      molecular DNA tree based on a matrix composed of concatenated rRNA sequences,
      strain GeoM*662 showed a close relationship to other species of Durinskia, and
      the freshwater species clearly differs from the marine members. Two independent
      colonization events from the marine into the freshwater environment can be
      inferred within the Kryptoperidiniaceae. We provide a summarizing cladogram of
      dinophytes harboring a diatom as endosymbiont with evolutionary novelties
      indicated as well as a morphological key to the 6 species of Durinskia that are
      currently accepted.

PMID- 29066289
TI  - Soybean saponin modulates nutrient sensing pathways and metabolism in zebrafish.
AB  - Soybean saponin (SA) is known as a major anti-nutritional factor that causes
      metabolic disturbances and growth reduction in fish. However, the mechanisms
      underlying these effects were far from fully understood. In particular, the
      influences of SA on nutrient sensing and downstream metabolic pathways remain
      largely unexplored. Using zebrafish as an animal model, this study was conducted
      to examine the phenotypic and molecular responses after dietary SA treatment for
      2 weeks. SA at both 5 and 10 g/kg diet levels significantly reduced growth
      performance and feed efficiency, and damaged the morphology of the intestinal
      mucosa. SA stimulated AMP-activated protein kinase but reduced target of
      rapamycin (TOR) activities in both feeding trial and cellular studies.
      Furthermore, SA increased the mRNA expressions of growth axis genes including
      growth hormone, insulin-like growth factor 1, growth hormone receptor A, and
      growth hormone receptor B, but decreased insulin-like growth factor-binding
      protein 2 at both mRNA and protein levels. SA also increased the expressions of
      key metabolic enzymes involved in glutamine synthetase, glutamate dehydrogenase
      and lipolysis, hormone-sensitive lipase and lipoprotein lipase. Our results
      demonstrated that SA modulated nutrient sensing pathways and metabolism, thus
      provide new aspects on the explanation of the physiological effects of SA.

PMID- 29066291
TI  - In silico assessment of the effects of various compounds in MEA/hiPSC-CM assays:
      Modeling and numerical simulations.
AB  - We propose a mathematical approach for the analysis of drugs effects on the
      electrical activity of human induced pluripotent stem cell-derived cardiomyocytes
      (hiPSC-CMs) based on multi-electrode array (MEA) experiments. Our goal is to
      produce an in silico tool able to simulate drugs action in MEA/hiPSC-CM assays.
      The mathematical model takes into account the geometry of the MEA and the
      electrodes' properties. The electrical activity of the stem cells at the ion
      channel level is governed by a system of ordinary differential equations (ODEs).
      The ODEs are coupled to the bidomain equations, describing the propagation of the
      electrical wave in the stem cells preparation. The field potential (FP) measured
      by the MEA is modeled by the extracellular potential of the bidomain equations.
      First, we propose a strategy allowing us to generate a field potential in good
      agreement with the experimental data. We show that we are able to reproduce
      realistic field potentials by introducing different scenarios of heterogeneity in
      the action potential. This heterogeneity reflects the differentiation
      atria/ventricles and the age of the cells. Second, we introduce a drug/ion
      channels interaction based on a pore block model. We conduct different
      simulations for five drugs (mexiletine, dofetilide, bepridil, ivabradine and
      BayK). We compare the simulation results with the field potential collected from
      experimental measurements. Different biomarkers computed on the FP are
      considered, including depolarization amplitude, repolarization delay,
      repolarization amplitude and depolarization-repolarization segment. The
      simulation results show that the model reflect properly the main effects of these
      drugs on the FP.

PMID- 29066290
TI  - Phenotype classification using the combination of lung sound analysis and
      fractional exhaled nitric oxide for evaluating asthma treatment.
AB  - BACKGROUND: We report the utility of combining lung sound analysis and fractional
      exhaled nitric oxide (FeNO) for phenotype classification of airway inflammation
      in patients with bronchial asthma. We investigated the usefulness of the
      combination of the expiration-to-inspiration sound power ratio in the mid
      frequency range (E/I MF) of 200-400 Hz and FeNO for comprehensively classifying
      disease type and evaluating asthma treatment. METHODS: A total of 233 patients
      with bronchial asthma were included. The cutoff values of FeNO and E/I MF were
      set to 38 ppb and 0.36, respectively, according to a previous study. The patients
      were divided into 4 subgroups based on the FeNO and E/I MF cutoff values.
      Respiratory function, the percentages of sputum eosinophils and neutrophils, and
      patient background characteristics were compared among groups. RESULTS:
      Respiratory function was well controlled in the FeNO low/E/I MF low group (good
      control). Sputum neutrophil was higher and FEV1,%pred was lower in the FeNO
      low/E/I MF high group (poor control). History of childhood asthma and atopic
      asthma were associated with the FeNO high/E/I MF low group (insufficient
      control). The FeNO high/E/I MF high group corresponded to a longer disease
      duration, increased blood or sputum eosinophils, and lower FEV1/FVC (poor
      control). CONCLUSIONS: The combination of FeNO and E/I MF assessed by lung sound
      analysis allows the condition of airway narrowing and the degree of airway
      inflammation to be assessed in patients with asthma and is useful for evaluating
      bronchial asthma treatments.

PMID- 29066294
TI  - Semi-parametric arterial input functions for quantitative dynamic contrast
      enhanced magnetic resonance imaging in mice.
AB  - OBJECTIVE: An extension of single- and multi-channel blind deconvolution is
      presented to improve the estimation of the arterial input function (AIF) in
      quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).
      METHODS: The Lucy-Richardson expectation-maximization algorithm is used to obtain
      estimates of the AIF and the tissue residue function (TRF). In the first part of
      the algorithm, nonparametric estimates of the AIF and TRF are obtained. In the
      second part, the decaying part of the AIF is approximated by three decaying
      exponential functions with the same delay, giving an almost noise free semi
      parametric AIF. Simultaneously, the TRF is approximated using the adiabatic
      approximation of the Johnson-Wilson (aaJW) pharmacokinetic model. RESULTS: In
      simulations and tests on real data, use of this AIF gave perfusion values close
      to those obtained with the corresponding previously published nonparametric AIF,
      and are more noise robust. CONCLUSION: When used subsequently in voxelwise
      perfusion analysis, these semi-parametric AIFs should give more correct perfusion
      analysis maps less affected by recording noise than the corresponding
      nonparametric AIFs, and AIFs obtained from arteries. SIGNIFICANCE: This paper
      presents a method to increase the noise robustness in the estimation of the
      perfusion parameter values in DCE-MRI.

PMID- 29066293
TI  - The Mental Activity and eXercise (MAX) trial: Effects on physical function and
      quality of life among older adults with cognitive complaints.
AB  - BACKGROUND: Older adults with cognitive complaints are vulnerable to dementia,
      physical impairments, and poor quality of life. Exercise and mental activity may
      improve physical function and health-related quality of life (HRQOL) but
      combinations have not been investigated systematically. The Mental Activity and
      eXercise (MAX) trial found that mental activity plus exercise over 12weeks
      improved cognitive function (primary outcome) in sedentary older adults with
      cognitive complaints. OBJECTIVE: To investigate the effects of combinations of
      two mental activity and exercise programs on physical function and HRQOL
      (secondary outcomes). METHODS: Participants (n=126, age 73+/-6years, 65% women)
      were randomized to 12weeks of exercise (aerobic exercise or stretching/toning,
      3*60min/week) plus mental activity (computer-based cognitive training or
      educational DVDs, 3*60min/week) using a factorial design. Assessments included
      the Senior Fitness Test (physical function), Short Form-12 physical and mental
      sub-scales (HRQOL), and CHAMPS questionnaire (physical activity). RESULTS: There
      were no differences between groups at baseline (p>0.05). We observed improvements
      over time in most physical function measures [chair stands (p-for-time=0.001),
      arm curls (p-for-time<0.001), step test (p-for-time=0.003), sit & reach (p-for
      time=0.01), and back scratch (p-for-time=0.04)] and in physical HRQOL (p-for
      time=0.04). There were no differences in change between groups (group*time
      p>0.05). Changes in most physical function measures and physical HRQOL correlated
      with physical activity changes. CONCLUSION: Combined mental activity and exercise
      interventions of various types can improve both physical function and physical
      HRQOL among sedentary older adults with cognitive complaints. Exercise control
      group design should be carefully considered as even light exercise may induce
      benefits in vulnerable older adults.

PMID- 29066292
TI  - Rem2 signaling affects neuronal structure and function in part by regulation of
      gene expression.
AB  - The central nervous system has the remarkable ability to convert changes in the
      environment in the form of sensory experience into long-term alterations in
      synaptic connections and dendritic arborization, in part through changes in gene
      expression. Surprisingly, the molecular mechanisms that translate neuronal
      activity into changes in neuronal connectivity and morphology remain elusive.
      Rem2, a member of the Rad/Rem/Rem2/Gem/Kir (RGK) subfamily of small Ras-like
      GTPases, is a positive regulator of synapse formation and negative regulator of
      dendritic arborization. Here we identify that one output of Rem2 signaling is the
      regulation of gene expression. Specifically, we demonstrate that Rem2 signaling
      modulates the expression of genes required for a variety of cellular processes
      from neurite extension to synapse formation and synaptic function. Our results
      highlight Rem2 as a unique molecule that transduces changes in neuronal activity
      detected at the cell membrane to morphologically relevant changes in gene
      expression in the nucleus.

PMID- 29066295
TI  - Corrigendum to "Age of menarche is associated with knee joint replacement due to
      primary osteoarthritis (The HUNT Study and the Norwegian Arthroplasty Register)"
      [Osteoarthr Cartil 25 (2017) 1654-1662].

PMID- 29066296
TI  - Two novel bioactive sulfated guaiane sesquiterpenoid salt alkaloids from the
      aerial parts of Scorzonera divaricata.
AB  - : Extracts of the aerial parts of Scorzonera divaricata afforded sulfoscorzonin D
      (1) and sulfoscorzonin E (2), two novel pyrrolidine inner salt alkaloids with a
      sulfated guaiane sesquiterpene lactone nucleus, along with 22 known compounds.
      Especially, sulfoscorzonin D containing a unusual monoterpene moiety is very
      rare. The structures of new compounds were established using spectroscopic
      analysis including one- and two-dimensional NMR and HRESIMS. The cytotoxicities
      of compounds 1-4 and 10 against three tumor cell lines (K562, Hela, and HepG2)
      were evaluated using the MTT assay. Compounds 2 and 10 exhibited moderate
      cytotoxic activity. The biological properties of 1-3, 5-8, 10-14, and 16-24, were
      screened against nine different gram-positive and gram-negative bacteria.
      Compounds 1, 5-8, 10, and 18, showed potent antibacterial activities. CHEMICAL
      COMPOUNDS STUDIED IN THIS ARTICLE: Glucozaluzanin C (PubChem CID: 442320);
      1beta,4alpha-dihydroxy-5alpha,6beta,7alpha,11betaH-eudermn-12; 6-olide (CID:
      11119093); oleanolic acid (CID: 10494); lup-20(29)-ene-3beta,28-diol (CID:
      72326); (22E)-5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-ol (CID: 5469431);
      ergosta-3beta,5alpha, 6beta-trialcohol (CID: 44558918); stigma-5-en-3-O-beta
      glucoside (CID: 5742590); vomifoliol (CID: 12444927); trans-caffeic acid (CID:
      689043); trans-p-hydroxy coumaric acid (CID: 637542); 4-hydroxy-3-methoxyphenyl
      ferulate (CID: 11500646); 7,3',4'-trihydroxyflavonol (CID: 5281614); tricin (ID:
      5281702); luteolin (CID: 5280445); diosmetin (CID: 5281612); 5,7-dihydroxy-8
      methoxyflavone (CID: 5281703); 5,7-dihydroxy-6-methoxyflavone (CID: 5320315);
      methyl-3,4-dihydroxy benzoate (CID: 287064); m-hydroxy benzoic acid (CID: 7420);
      7-hydroxy-coumarin (CID: 5281426); and scopoletin (CID: 5280460).

PMID- 29066297
TI  - Medicinal Mascarene Aloes: An audit of their phytotherapeutic potential.
AB  - A phytochemical and biological investigation of the endemic Mascarene Aloes (Aloe
      spp.), including A. tormentorii (Marais) L.E.Newton & G.D.Rowley, A. purpurea
      Lam, A. macra Haw., A. lomatophylloides Balf.f and A. vera (synonym A.
      barbadensis Mill.), which are used in the traditional folk medicine of the
      Mascarene Islands, was initiated. Methanolic extracts of the Aloes under study
      were analysed using high resolution LC-UV-MS/MS and compounds belonging to the
      class of anthraquinones, anthrones, chromones and flavone C-glycosides were
      detected. The Mascarene Aloes could be distinguished from A. vera by the absence
      of 2"-O-feruloylaloesin and 7-O-methylaloeresin. GC-MS analysis of
      monosaccharides revealed the presence of arabinose, fucose, xylose, mannose and
      galactose in all the Mascarene Aloes and in A. vera. The crude extracts of all
      Aloes analysed displayed antimicrobial activity against Bacillus cereus,
      Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Only extracts
      of A. macra were active against P. aeruginosa and Klebsiella pneumoniae, while
      none of the Aloe extracts inhibited Propionibacterium acnes. A. macra displayed
      anti-tyrosinase activity, exhibiting 50% inhibition at 0.95mg/mL, and extracts of
      A. purpurea (Mauritius) and A. vera displayed activity in a wound healing-scratch
      assay. In vitro cytotoxicity screening of crude methanolic extracts of the Aloes,
      using the MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide)
      showed that only A. purpurea (Reunion) elicited a modest toxic effect against
      HL60 cells, with a percentage toxicity of 8.2% (A. purpurea-Reunion) and none of
      the Aloe extracts elicited a toxic effect against MRC 5 fibroblast cells at a
      concentration of 0.1mg/mL. Mascarene Aloe species possess noteworthy
      pharmacological attributes associated with their rich phytochemical profiles.

PMID- 29066298
TI  - Sulfur-containing compounds from the roots of Ferula latisecta and their
      cytotoxic activities.
AB  - Five new sulfur-containing compounds, with a new geometry (cis) of the propenyl
      moiety, and five known compounds were isolated from the roots of Ferula
      latisecta. The structures of these compounds, were elucidated on the basis of
      spectroscopic data including 1D and 2D NMR experiments and HRMS. All of the
      isolated compounds were tested against A2780, A549, HeLa, and HCT116 human cancer
      cell lines and some of them showed moderate cytotoxic activities.

PMID- 29066299
TI  - beta-elemene attenuates macrophage activation and proinflammatory factor
      production via crosstalk with Wnt/beta-catenin signaling pathway.
AB  - beta-elemene, extracted from Rhizoma zedoariae, has been widely used as a
      traditional medicine for its antitumor activity against a broad range of cancers.
      However, the effect of beta-elemene in inflammation disorders has yet to be
      determined. The present study was designed to investigate the anti-inflammatory
      effects and potential molecular mechanisms of beta-elemene in lipopolysaccharide
      (LPS)-induced murine macrophage cells RAW264.7. We found that the production of
      pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta), induced by LPS was
      significantly suppressed by beta-elemene in a dose-dependent manner in RAW264.7
      macrophage cell line. Also, beta-elemene inhibited LPS-induced nitric oxide
      synthase (iNOS) and interleukin-10 (IL-10) expression by RAW264.7, which was
      related to the down-regulation of Wnt/beta-catenin signaling pathway.
      Importantly, this study demonstrates that beta-catenin was significantly
      inhibited by beta-elemene, which appeared to be largely responsible for the down
      regulation of Wnt/beta-catenin signaling pathway. Accordingly, the deletion of
      beta-catenin in primary macrophages reversed beta-catenin-elicited inhibition of
      immune response. Furthermore, beta-catenin expression and Wnt/beta-catenin
      signaling pathway induced by LPS in RAW264.7 was also significantly inhibited by
      alpha-humulene, one isomeric sesquiterpene of beta-elemene. alpha-humulene was
      also found to significantly inhibit LPS-induced production of proinflammatory
      cytokines. However, alpha-humulene showed more cytotoxic ability than beta
      elemene. Collectively, our data illustrated that beta-elemene exerted a potent
      inhibitory effect on pro-inflammatory meditator and cytokines production via the
      inactivation of beta-catenin, and also demonstrated the protective functions of
      beta-elemene in endotoxin-induced inflammation. beta-elemene may serve as
      potential nontoxic modulatory agents for the prevention and treatment of
      inflammatory diseases.

PMID- 29066300
TI  - Upregulation of functional Kv11.1a isoform expression by modified U1 small
      nuclear RNA.
AB  - The KCNH2 or human ether-a go-go-related gene (hERG) encodes the Kv11.1 potassium
      channel that conducts the rapidly activating delayed rectifier potassium current
      in the heart. The expression of Kv11.1 C-terminal isoforms is directed by the
      alternative splicing and polyadenylation of intron 9. Splicing of intron 9 leads
      to the formation of a functional, full-length Kv11.1a isoform and polyadenylation
      of intron 9 results in the production of a non-functional, C-terminally truncated
      Kv11.1a-USO isoform. The relative expression of Kv11.1a and Kv11.1a-USO plays an
      important role in regulating Kv11.1 channel function. In the heart, only one
      third of KCNH2 pre-mRNA is processed to Kv11.1a due to the weak 5' splice site of
      intron 9. We previously showed that the weak 5' splice site is caused by sequence
      deviation from the consensus, and that mutations toward the consensus sequence
      increased the efficiency of intron 9 splicing. It is well established that 5'
      splice sites are recognized by complementary base-paring with U1 small nuclear
      RNA (U1 snRNA). In this study, we modified the sequence of U1 snRNA to increase
      its complementarity to the 5' splice site of KCNH2 intron 9 and observed a
      significant increase in the efficiency of intron 9 splicing. RNase protection
      assay and western blot analysis showed that modified U1 snRNA increased the
      expression of the functional Kv11.1a isoform and concomitantly decreased the
      expression of the non-functional Kv11.1a-USO isoform. In patch-clamp experiments,
      modified U1 snRNA significantly increased Kv11.1 current. Our findings suggest
      that relative expression of Kv11.1 C-terminal isoforms can be regulated by
      modified U1 snRNA.

PMID- 29066301
TI  - Wild-type catalase peroxidase vs G279D mutant type: Molecular basis of Isoniazid
      drug resistance in Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis katG gene is responsible for production of an enzyme
      catalase peroxidase that peroxidises and activates the prodrug Isoniazid (INH), a
      first-line antitubercular agent. INH interacts with catalase peroxidase enzyme
      within its heme pocket and gets converted to an active form. Mutations occurring
      in katG gene are often linked to reduced conversion rates for INH. This study is
      focussed on one such mutation occurring at residue 279, where glycine often
      mutates to aspartic acid (G279D). In the present study, several structural
      analyses were performed to study the effect of this mutation on functionality of
      KatG protein. On comparison, mutant protein exhibited a lower docking score,
      smaller binding cavity and reduced affinity towards INH. Molecular dynamics
      analysis revealed the mutant to be more rigid and less compact than the native
      protein. Essential dynamics analysis determined correlated motions of residues
      within the protein structure. G279D mutant was found to have many residues that
      showed related motions and an undesirable effect on the functionality of protein.

PMID- 29066302
TI  - De novo transcriptomic analysis during Lentinula edodes fruiting body growth.
AB  - The fruiting body of Lentinula edodes is a popular edible mushroom, and extracts
      from the mycelium and the fruiting body of this species have diverse therapeutic
      potential. To gain insights into the molecular mechanisms underlying the fruiting
      body growth of L. edodes from the early bud stage (EBS), through the intermediate
      developing stage (IDS), to the fully developed stage (FDS), we performed de novo
      transcriptomic analysis using high-throughput Illumina RNA-sequencing. First, we
      generated three cDNA libraries representative of the three respective stages. We
      then obtained 38,933,148, 44,594,472, and 37,905,646 high-quality reads from the
      respective libraries and assembled the reads into 25,104 transcriptional contigs,
      containing 15,199 unigenes. We found that only 9331 of the unigenes had been
      annotated in the NCBI non-redundant protein database, and we functionally
      annotated 4758 of them through Gene Ontology (GO) analysis and 2921 of them
      through Clusters of Orthologous Groups of proteins (COGs) analysis. We also
      assigned 3995 unigenes to metabolic pathways by using the Kyoto Encyclopedia of
      Genes and Genomes (KEGG). We further identified 399 differentially expressed
      genes (DEGs) between EBS and IDS, 1428 between IDS and FDS, and 1830 between EBS
      and FDS, uncovering 769 DEGs in multiple metabolic and signaling pathways.
      Interestingly, there were a limited number of DEGs whose expression was
      dramatically associated with FDS. Finally, genes, whose expression was either
      highly up-regulated in FDS or remained at a high level during fruiting body
      growth, were annotated specifically in the pathways of purine metabolism,
      unsaturated fatty acid metabolism and meiosis, suggesting that these key
      molecular events were actively occurring in the fruiting body. Our work is the
      first high-throughput transcriptome study on the growth of L. edodes fruiting
      bodies, and the results uncovered candidate genes for future gene identification
      and utilization of this commercially and medically important mushroom.

PMID- 29066304
TI  - Regulation of lipid metabolism in adipose depots of fat-tailed and thin-tailed
      lambs during negative and positive energy balances.
AB  - This study aimed to evaluate the effects of negative and positive energy balances
      on gene expression of regulators and enzymes controlling lipogenesis and
      lipolysis in muscle and adipose depots of fat-tailed and thin-tailed lambs. Lambs
      were slaughtered during neutral, negative and positive energy balances for sample
      collection. Real time q-PCR was conducted to measure the gene expression.
      Expression of PPARgamma was increased in response to positive energy balance
      regardless of genotype and type of tissue (P<0.04). Expression of SREBF1 was
      reduced in response to negative and positive energy balances in fat-tailed lambs,
      whereas in thin-tailed lambs, downregulated SREBF1 was restored during positive
      energy balance (P<0.01). Enhancement in FABP4 expression in response to negative
      and positive energy balances was respectively higher in thin-tailed and fat
      tailed lambs affected by interaction of genotype and energy balance (P<0.11). In
      thin-tailed lambs, the enhanced FABP4 expression in response to negative energy
      balance was considerably higher in mesenteric adipose depot, whereas in fat
      tailed lambs, positive energy balance induced enhancement in FABP4 expression was
      considerably higher in fat-tail adipose depot. The results demonstrate that
      transcription regulation of lipogenesis and lipolysis during negative and
      positive energy balances occurs differently in fat-tailed and thin-tailed lambs.
      Thin-tailed and fat-tailed lambs are respectively more responsive to negative and
      positive energy balances and mesenteric and fat-tail adipose depots respectively
      in thin-tailed and fat-tailed lambs are the main adipose depots responsible for
      higher responsiveness of thin-tailed and fat-tailed lambs to negative and
      positive energy balances.

PMID- 29066303
TI  - Computational insights into promoter architecture of toxin-antitoxin systems of
      Mycobacterium tuberculosis.
AB  - Toxin-antitoxin (TA) systems are two component genetic modules widespread in many
      bacterial genomes, including Mycobacterium tuberculosis (Mtb). The TA systems
      play a significant role in biofilm formation, antibiotic tolerance and
      persistence of pathogen inside the host cells. Deciphering regulatory motifs of
      Mtb TA systems is the first essential step to understand their transcriptional
      regulation. In this study, in silico approaches, that is, the knowledge based
      motif discovery and de novo motif discovery were used to identify the regulatory
      motifs of 79 Mtb TA systems. The knowledge based motif discovery approach was
      used to design a Perl based bio-tool Mtb-sig-miner available at
      (https://github.com/zoozeal/Mtb-sig-miner), which could successfully detect sigma
      (sigma) factor specific regulatory motifs in the promoter region of Mtb TA
      modules. The manual curation of Mtb-sig-miner output hits revealed that the
      majority of them possessed sigmaB regulatory motif in their promoter region. On
      the other hand, de novo approach resulted in the identification of a novel
      conserved motif [(T/A)(G/T)NTA(G/C)(C/A)AT(C/A)] within the promoter region of 14
      Mtb TA systems. The identified conserved motif was also validated for its
      activity as conserved core region of operator sequence of corresponding TA system
      by molecular docking studies. The strong binding of respective antitoxin/toxin
      with the identified novel conserved motif reflected the validation of identified
      motif as the core region of operator sequence of respective TA systems. These
      findings provide computational insight to understand the transcriptional
      regulation of Mtb TA systems.

PMID- 29066305
TI  - Testing an association between TLR4 and CXCR1 gene polymorphisms with
      susceptibility to urinary tract infection in type 2 diabetes in north Indian
      population.
AB  - BACKGROUND: Genetic variations of Toll like receptor 4 (TLR4) and CXC-chemokine
      receptor type1 (CXCR1), the key elements of innate immune system and their
      association with urinary tract infection (UTI) were studied in general
      population. In present study we investigate genetic variation of these genes in
      diabetic patients (3 to 4 times higher prevalence of UTI in comparison to general
      population). METHODS: A total 1100 subjects (318 diabetic patients with UTI, 324
      diabetic patients without UTI, 200 non-diabetic UTI patients and 260 age matched
      healthy control) were enrolled in the study. SNPs of TLR4 rs4986790, rs4986791
      and CXCR1 rs2234671 was assessed by PCR-RFLP and PCR-SSP respectively. RESULTS:
      Statistical analysis revealed that A/G genotype and G allele of TLR4 rs4986790
      are significantly associated with UTI in both diabetics and nondiabetic patients
      in comparison to healthy control. Similarly CT genotype and T allele of TLR4
      rs4986791 are also significantly associated with UTI in both groups. We also
      found that prevalence of A/G genotype of TLR4 rs4986790 and CT genotype of TLR4
      rs4986791 are significantly higher in patients of diabetes with UTI in comparison
      to diabetic patients without UTI. We did not find any association of CXCR1
      rs2234671 polymorphism with UTI by comparing with any group. CONCLUSION: We found
      that TLR4 rs4986790 and rs4986791 gene polymorphism is a risk for UTI development
      in both diabetic and nondiabetic patients in north Indian population.

PMID- 29066306
TI  - SFRP5 is a target gene transcriptionally regulated by PPARgamma in 3T3-L1
      adipocytes.
AB  - Secreted frizzled-related protein 5 (SFRP5) is a newly identified adipokine.
      SFRP5 expression increases during the differentiation and maturation of
      adipocytes, but the factors regulating SFRP5 expression during this process
      remain unclear. This study showed that peroxisome proliferator-activated receptor
      gamma (PPARgamma) adenovirus transfection could enhance the SFRP5 expression of
      3T3-L1 adipocytes. Three potential binding sites of PPARgamma in the SFRP5
      promoter domain were found by bioinformatics analysis. Luciferase reporter gene
      assay demonstrated that PPARgamma regulated the activity of the SFRP5 promoter
      through cis-acting elements at -2,284--1,500bp. Further experiments verified that
      PPARgamma could specifically bind to the SFRP5 promoter at -2,284--2,263bp using
      chromatin immunoprecipitation and electrophoretic mobility shift assay. These
      results suggest that SFRP5 be a target gene of PPARgamma, and its expression may
      be under the transcriptional regulation of PPARgamma.

PMID- 29066307
TI  - Aromatase Inhibitors Are Associated With Low Sexual Desire Causing Distress and
      Fecal Incontinence in Women: An Observational Study.
AB  - BACKGROUND: Little is known of the impact of aromatase inhibitor (AI) therapy on
      sexual and pelvic floor function. AIM: To document the prevalence of, and factors
      associated with, low desire, sexually related personal distress, hypoactive
      sexual desire dysfunction (HSDD), and pelvic floor dysfunction in women 10 years
      after breast cancer diagnosis. METHODS: This was a prospective, observational,
      community-based cohort study of Australian women with invasive breast cancer
      recruited within 12 months of diagnosis. 1,053 of the 1,305 who completed the
      initial 5 years of study follow-up agreed to be re-contacted, and 992 of these
      women alive 10 years after diagnosis were sent the study questionnaire. OUTCOMES:
      The main outcome measure was HSDD determined by a score no higher than 5.0 on the
      desire domain of the Female Sexual Function Index (FSFI) plus a score of at least
      11.0 on the Female Sexual Distress Scale-Revised (FSDS-R). Pelvic floor
      disorders, including urinary incontinence, fecal incontinence, and pelvic organ
      prolapse, were assessed using validated questionnaires. Multivariable logistic
      regression was used to assess factors associated with low desire, personal
      distress, and HSDD. RESULTS: 625 completed questionnaires were returned. The
      respondents' median age was 65.1 years (range = 36.4-95.5). Current AI use was
      reported by 10% and tamoxifen use was reported by 3.4%. 521 of the 608 women
      (85.7%; 95% CI = 82.9-88.5) who competed the FSFI desire domain had low sexual
      desire, and 246 of the 563 women (43.7%; 95% CI = 39.6-47.8%) who completed the
      FSDS-R had sexually related personal distress. 221 of the 559 women (39.5%; 95%
      CI = 35.5-43.6%) who completed the 2 questionnaires had HSDD. Current AI users
      were more likely to have HSDD than non-users (55.2% [95% CI = 42.2-68.1] vs 37.8%
      [95% CI = 33.5-42.0]; P = .01). HSDD was more prevalent in sexually active,
      current AI users (66.7%; 95% CI = 49.4-83.9) vs current non-users (43.6%; 95% CI
      = 37.0-50.2; P = .02). In a logistic regression model, HSDD was significantly
      associated with current AI use and inversely associated with age. Fecal
      incontinence was more prevalent in AI users than in current non-users (29.8% [95%
      CI = 17.8-41.8] vs 16.4% [95% CI = 13.2-19.6], respectively; P = .01). CLINICAL
      IMPLICATIONS: It is important to address women's sexual health even many years
      after their breast cancer diagnosis. STRENGTHS AND LIMITATIONS: Strengths include
      a representative sample, use of validated questionnaires, and few missing data.
      Limitations include sexual activity being a 4-week recall. CONCLUSIONS: AI use is
      associated with HSDD and fecal incontinence in women who are 10 years after
      breast cancer diagnosis. Robinson PJ, Bell RJ, Christakis MK, et al. Aromatase
      Inhibitors Are Associated With Low Sexual Desire Causing Distress and Fecal
      Incontinence in Women: An Observational Study. J Sex Med 2017;14:1566-1574.

PMID- 29066308
TI  - Synthesis and anti-HCV activity of a series of beta-d-2'-deoxy-2'-dibromo
      nucleosides and their corresponding phosphoramidate prodrugs.
AB  - Several beta-d-2'-deoxy-2'-substituted nucleoside analogs have displayed potent
      and selective anti-HCV activities and some of them have reached human clinical
      trials. In that regard, we report herein the synthesis of a series of 2'-deoxy,2'
      dibromo substituted U, C, G and A nucleosides 10a-d and their corresponding
      phosphoramidate prodrugs 13a-d. The synthesized nucleosides 10a-d and prodrugs
      13a-d were evaluated for their inhibitory activity against HCV as well as
      cellular toxicity. The results showed that the most potent compound was prodrug
      13a, which exhibited micromolar inhibitory activity (EC50 = 1.5 +/- 0.8 uM) with
      no observed toxicity. In addition, molecular modeling and free energy
      perturbation calculations for the 5'-triphosphate formed from 13a and related 2'
      modified nucleotides are discussed.

PMID- 29066309
TI  - Discovery and evaluation of Cav3.1-selective T-type calcium channel blockers.
AB  - We identified and characterized a series of pyrazole amides as potent, selective
      Cav3.1-blockers. This series culminated with the identification of pyrazole
      amides 5a and 12d, with excellent potencies and/or selectivities toward the
      Cav3.2- and Cav3.3-channels. This compound displays poor DMPK properties, making
      its use difficult for in vivo applications. Nevertheless, this compound as well
      as analogous ones are well-suited for in vitro studies.

PMID- 29066310
TI  - Synapsin I deletion reduces neuronal damage and ameliorates clinical progression
      of experimental autoimmune encephalomyelitis.
AB  - The classical view of multiple sclerosis (MS) pathogenesis states that
      inflammation-mediated demyelination is responsible for neuronal damage and loss.
      However, recent findings show that impairment of neuronal functions and
      demyelination can be independent events, suggesting the coexistence of other
      pathogenic mechanisms. Due to the inflammatory milieu, subtle alterations in
      synaptic function occur, which are probably at the basis of the early cognitive
      decline that often precedes the neurodegenerative phases in MS patients. In
      particular, it has been reported that inflammation enhances excitatory synaptic
      transmission while it decreases GABAergic transmission in vitro and ex vivo. This
      evidence points to the idea that an excitation/inhibition imbalance occurs in the
      inflamed MS brain, even though the exact molecular mechanisms leading to this
      synaptic dysfunction are as yet not completely clear. Along this line, we
      observed that acute treatment of primary hippocampal neurons in culture with pro
      inflammatory cytokines leads to an increased phosphorylation of synapsin I (SynI)
      by ERK1/2 kinase and to an increase in the frequency of spontaneous synaptic
      vesicle release events, which is prevented by SynI deletion. In vivo, the
      ablation of SynI expression is protective in terms of disease progression and
      neuronal damage in the experimental autoimmune encephalomyelitis mouse model of
      MS. Our results point to a possible key role in MS pathogenesis of the neuronal
      protein SynI, a regulator of excitation/inhibition balance in neuronal networks.

PMID- 29066311
TI  - Comment about the article: "Association of metabolic syndrome with low birth
      weight, intake of high-calorie diets and acanthosis nigricans in children and
      adolescents with overweight and obesity".

PMID- 29066312
TI  - Dicer1 ablation in osterix positive bone forming cells affects cortical bone
      homeostasis.
AB  - The RNAse III enzyme Dicer plays a major role in the processing of microRNAs from
      large pre-miRNAs. Dicer1 processed microRNAs are known to play a comprehensive
      role in osteoblast differentiation, bone remodeling and skeletal disorders.
      Targeted deletion of Dicer1 in osteo-progenitor cells is deleterious to fetal
      survival whereas targeted deletion in mature osteoblasts leads to an increase in
      bone mass. To address the role of Dicer1 in post-natal skeletal homeostasis, we
      generated a pre-osteoblast specific Dicer1 knockout model employing Tamoxifen
      controllable Cre allele, enabling us, via tamoxifen administration, to time
      controllably ablate Dicer1 gene expression in osterix expressing bone forming
      cells in post-natal mice. Inactivation of Dicer1 in osterix positive bone forming
      cells led to striking dysregulation of cortical bone formation in pre-pubertal as
      well as adult mice. Cortical bone thickness was found to be significantly
      decreased in the Cre+ femora of both young and adult mice. Further, biomechanical
      testing experiments showed increased ductility, reduced stiffness and altered
      load at upper yield among the Cre+ tibiae. Our results suggest that Dicer1
      processed microRNAs might play an important role in the regulation of post-natal
      cortical bone formation.

PMID- 29066314
TI  - MALDI-TOF mass spectrometry-based identification of Listeria species in
      surveillance: A prospective study.
AB  - This study aimed to evaluate MALDI-TOF MS for species discrimination of Listeria
      in the context of routine surveillance. MALDI-TOF MS yielded 100% accuracy for
      the identification of L. monocytogenes, L. innocua, L. ivanovii, L.
      fleischmannii, L. grayi, L. seeligeri, L. weihenstephanensis and L. welshimeri,
      as confirmed by whole genome sequence analyses.

PMID- 29066313
TI  - Ex vivo replication of phenotypic functions of osteocytes through biomimetic 3D
      bone tissue construction.
AB  - Osteocytes, residing as 3-dimensionally (3D) networked cells in bone, are well
      known to regulate bone and mineral homeostasis and have been recently implicated
      to interact with cancer cells to influence the progression of bone metastases. In
      this study, a bone tissue consisting of 3D-networked primary human osteocytes and
      MLO-A5 cells was constructed using: (1) the biomimetic close-packed assembly of
      20-25MUm microbeads with primary cells isolated from human bone samples and MLO
      A5 cells and (2) subsequent perfusion culture in a microfluidic device. With this
      3D tissue construction approach, we replicated ex vivo, for the first time, the
      mechanotransduction function of human primary osteocytes and MLO-A5 cells by
      correlating the effects of cyclic compression on down-regulated SOST and DKK1
      expressions. Also, as an example of using our ex vivo model to evaluate
      therapeutic agents, we confirmed previously reported findings that parathyroid
      hormone (PTH) decreases SOST and increases the ratio of RANKL and OPG. In
      comparison to other in vitro models, our ex vivo model: (1) replicates the cell
      density, phenotype, and functions of primary human osteocytes and MLO-A5 cells
      and (2) thus provides a clinically relevant means of studying bone diseases and
      metastases.

PMID- 29066315
TI  - Surgery Website as a 24/7 Adjunct to a Surgical Curriculum.
AB  - OBJECTIVE: Successfully teaching duty hour restricted trainees demands engaging
      learning opportunities. Our surgical educational website and its associated
      assets were assessed to understand how such a resource was being used. DESIGN:
      Our website was accessible to all Mayo Clinic employees via the internal web
      network. Website access data from April 2015 through October 2016 were
      retrospectively collected using Piwik. SETTING: Academic, tertiary care referral
      center with a large general surgery training program. Mayo Clinic, Rochester, MN.
      PARTICIPANTS: A total of 257 Mayo Clinic employees used the website. RESULTS: The
      website had 48,794 views from 6313 visits by 257 users who spent an average of 14
      +/- 11 minutes on the website. Our website houses 295 videos, 51 interactive
      modules, 14 educational documents, and 7 flashcard tutorials. The most popular
      content type was videos, with a total of 30,864 views. The most popular visiting
      time of the day was between 8 pm and 9 pm with 6358 views (13%), and Thursday was
      the most popular day with 17,907 views (37%).  A total of 78% of users accessed
      content beyond the homepage. Average visits peaked in relation to 2 components of
      our curriculum: a 240% increase one day before our biannual intern simulation
      assessments, and a 61% increase one day before our weekly conducted Friday
      simulation sessions. Interns who rotated on the service of the staff surgeon who
      actively endorses the website had 93% more actions per visit as compared to other
      users. The highest clicks were on the home banner for our weekly simulation
      session pre-emptive videos, followed by "groin anatomy," and "TEP hernia repair"
      videos. CONCLUSIONS: Our website acted as a "just-in-time" accessible portal to
      reliable surgical information. It supplemented the time sensitive educational
      needs of our learners by serving as a heavily used adjunct to 3 components of our
      surgical education curriculum: weekly simulation sessions, biannual assessments,
      and clinical rotations.

PMID- 29066316
TI  - Management of Primary Bilateral Trigeminal Neuralgia with Microvascular
      Decompression: 13-Case Series.
AB  - BACKGROUND: Bilateral trigeminal neuralgia is a relatively rare disease.
      Microvascular decompression (MVD) is a safe and effective treatment for
      unilateral trigeminal neuralgia; however, its utility in bilateral trigeminal
      neuralgia is unclear. Here, we report our experience with MVD in 13 cases of
      primary bilateral trigeminal neuralgia. METHODS: We retrospectively analyzed 13
      cases of bilateral trigeminal neuralgia that were treated with MVD between
      January 2013 and January 2015. Surgical outcomes and complications were explored
      in each case. RESULTS: Postoperatively, 11 patients had excellent outcomes and 2
      patients had good outcomes on the operative side. Three patients also reported
      the amelioration of contralateral symptoms after MVD. Of 10 cases indicating no
      contralateral improvement, 1 refused to undergo a second MVD procedure on the
      opposite side and 9 underwent a second MVD procedure and experienced symptom
      relief. The superior cerebellar artery was the most common offending vessel.
      There were no severe MVD-related complications. CONCLUSION: Vascular compression
      plays a causative role in bilateral and unilateral trigeminal neuralgia. MVD
      appears to be a safe and effective treatment option in patients who are
      refractory to pharmacotherapy.

PMID- 29066317
TI  - Does Advanced Age Affect the Outcomes of Stereotactic Radiosurgery for Cerebral
      Arteriovenous Malformation?
AB  - BACKGROUND: Stereotactic radiosurgery (SRS) is generally considered a minimally
      invasive treatment modality. However, definitive evidence of the efficacy of SRS
      in the elderly population is still not available. METHODS: The outcomes of 561
      elderly and nonelderly patients who underwent SRS for AVM at our institution
      between 1990 and 2013 were reviewed, analyzed, and compared. Elderly patients
      were defined as those age >=60 years at the time of SRS. RESULTS: The elderly
      cohort comprised 55 patients; the nonelderly cohort, 506. In the elderly cohort,
      the median age was 65 years, and the duration of follow-up was 91 months. The
      actuarial obliteration rates were 47% at 3 years, 70% at 4 years, and 76% at 5
      years in the elderly cohort, and 57% at 3 years, 76% at 4 years, and 83% at 5
      years in the nonelderly cohort. In the elderly cohort, the hemorrhage rates
      during the post-SRS latent phase were 5.2%/year in patients with hemorrhagic
      onset and 0%/year in those with nonhemorrhagic onset, and event-free survival
      (EFS) was 93% at 6 years and 89% at 12 years. The obliteration rate, mortality,
      and EFS rate were not significantly different between the 2 cohorts, whereas the
      rate of perifocal edema was significantly lower (P = 0.021) in the elderly
      cohort. The pre-SRS and post-SRS hemorrhage rates were slightly higher in the
      elderly cohort, albeit without statistical significance. CONCLUSIONS: Therapeutic
      effects and outcomes of SRS are similar in elderly and nonelderly patients.
      Treatment-related neurologic deficits are rare, and longer EFS can be expected.

PMID- 29066318
TI  - 5-ALA-Induced Fluorescence in Leptomeningeal Dissemination of Spinal Malignant
      Glioma.
AB  - BACKGROUND: 5-Aminolevulinic acid (5-ALA)-fluorescence-guided resection of
      malignant glioma is well established in many neuro-oncology departments. In
      addition, the use of 5-ALA has been reported for cerebral metastases, meningioma,
      and spinal tumors. We report a case of a patient with a leptomeningeal spread of
      a K27M-mutated spinal anaplastic astrocytoma (World Health Organization degrees 
      [WHO] III), which was detected by its faint 5-ALA-induced fluorescence. CASE
      DESCRIPTION: A 26-year-old female patient with an incomplete resection of a
      spinal astrocytoma (WHO II) at Th1-Th3 was treated with adjuvant combined
      radiotherapy/chemotherapy. After 4 years the patient suffered from a progressive
      paraplegia. Magnetic resonance imaging of the central nervous system showed no
      local progression of the spinal astrocytoma but an extensive disseminated
      leptomeningeal tumor formation. The cerebrospinal fluid of the patient obtained
      by lumbar puncture showed no indication of malignant cells in the cytopathologic
      examination. An open biopsy with preoperative administered 5-ALA with excision of
      the sensory nerve root from the cauda equina was performed. The biopsy showed a
      clearly light pink 5-ALA-induced fluorescence. The histopathologic examination
      confirmed a leptomeningeal spread of a K27M-mutated anaplastic astrocytoma (WHO
      degrees  III) without R132H-IDH1 mutation. CONCLUSIONS: Previous application of 5
      ALA might intraoperatively help to visualize and identify leptomeningeal spread.

PMID- 29066319
TI  - Predictive Factors of Headache Resolution After Chiari Type 1 Malformation
      Surgery.
AB  - BACKGROUND: Headache is the main and often isolated symptom of patients with
      Chiari type 1 malformation (CM1). Classically described as occipital and
      exacerbated by cough, headaches may be poorly characterized, making it difficult
      to establish CM1 as the underlying cause. Current guidelines for surgical
      posterior fossa decompression are undefined. The challenge is to distinguish
      headaches related to CM1 from headaches coincidentally coexisting with CM1. We
      aimed to determine predictive factors of headache resolution after surgery and
      applied to our cohort the Chiari Severity Index, a recently developed predictive
      prognostic score. METHODS: This retrospective study enrolled 49 patients with CM1
      and preoperative headache. Standardized telephone interviews regarding headaches
      before and after surgery were conducted by the same neurologist; magnetic
      resonance imaging morphometric analyses were performed by an independent
      neuroradiologist. Headache resolution was defined as >=50% reduction in frequency
      of headache days. RESULTS: Preoperative factors of headache resolution after
      multivariate analysis were attack duration <5 minutes (P = 0.001), triggering by
      Valsalva maneuvers (P = 0.003), severe intensity of attack (P = 0.05), occipital
      location (P = 0.05), and greater number of headache days per month (P = 0.04).
      These characteristics are part of International Headache Society diagnostic
      criteria for headache attributed to CM1. No radiologic predictive factor was
      demonstrated. Postoperative improvement was inversely correlated with Chiari
      Severity Index. CONCLUSIONS: This study confirms the relevance of International
      Headache Society criteria to identify headaches related to CM1. We propose their
      systematic use in a preoperative questionnaire.

PMID- 29066320
TI  - Detection of genetic alterations in cfDNA as a possible strategy to monitor the
      neoplastic progression of Barrett's esophagus.
AB  - Barrett's esophagus (BE) is associated with an increased risk of developing
      esophageal adenocarcinoma. Despite the low absolute risk of neoplastic
      progression of BE, probability increases with the diagnosis of dysplasia. For
      this reason, BE patients undergo an endoscopy-based surveillance that is,
      however, burdensome for patients, subject to inter-observer subjectivity, and
      expensive for national health systems. Thus, less invasive and low-cost
      diagnostic tools are needed. This study is aimed at finding a simple and reliable
      method to detect in the circulating cell-free DNA (cfDNA) of BE patients evidence
      of the molecular instability that accompanies BE carcinogenesis. We chose the
      loss of heterozygosity analysis because chromosomal region gains or losses have
      been described in BE and esophageal adenocarcinoma. Furthermore, this analysis
      does not require an a priori knowledge of tumor specific mutations and/or
      rearrangements. Previous data showed a good consistency between tissue and cfDNA
      alterations. Here, we report that, in the cfDNA of dysplastic BE patients, the
      frequency of genetic alterations is statistically higher than that of metaplastic
      BE patients (P = 0.005). Interestingly, after endoscopic treatment, the
      alteration frequency dropped, suggesting that cfDNA can also be used to monitor
      curative effects. Among the used markers, those that map nearby TP53 gene were
      the most discriminant between metaplastic and dysplastic BE. Furthermore,
      longitudinal follow-up cases showed that genetic alterations can be found in
      cfDNA before the appearance of a detectable lesion. Altogether, our data suggest
      that the use of liquid biopsy could become a minimally invasive diagnostic tool
      to implement BE patient monitoring.

PMID- 29066322
TI  - Alterations in Mesoscopic Oscillations affecting Episodic Memory following
      Developmental Traumatic Brain Injury.
AB  - Certain deficits of episodic memory among young adults are the delayed
      consequences of an earlier mild or moderate Traumatic Brain Injury (mTBI). We
      examined alterations in hippocampal Local Field Oscillations (LFOs) of
      equivalently-impaired juvenile rodents to identify reliable functional markers of
      single-incidence mTBI. Two persistent, behavior-dependent, electrophysiological
      markers of injury were identified in the absence of external physiological
      symptoms by the analysis of wirelessly-transmitted hippocampal LFOs (3-80Hz)
      during repeat measures of the Novel Object Recognition (NOR) paradigm. Using a
      new method for detecting functional network activity at a single recording site,
      we correlated instantaneous increases in theta frequency and gamma magnitude with
      injury during periods of functional network organization and dissolution,
      presented here as Theta Epochs (TEs) and Theta Non-Epochs (TNEs), respectively.
      We estimated the efficacy of networks across pairs of such sites using new
      metrics such as the Coherence of Theta Phase (PCOH) and Inter-Epoch Intervals
      (IEIs) and demonstrated that behavioral deficits observed during the NOR testing
      stage correspond to electrophysiological deficits recorded during the preceding
      NOR familiarization stage. Increased theta frequency during TNEs and increased
      smoothness of PCOH during TEs were found to be robust markers of injury during
      memory-reliant behaviors.

PMID- 29066325
TI  - A hitchhiker's guide to lesion-behaviour mapping.
AB  - Lesion-behaviour mapping is an influential and popular approach to anatomically
      localise cognitive brain functions in the human brain. Multiple considerations,
      ranging from patient selection, assessment of lesion location and patient
      behaviour, spatial normalisation, statistical testing, to the anatomical
      interpretation of obtained results, are necessary to optimize a lesion-behaviour
      mapping study and arrive at meaningful conclusions. Here, we provide a
      hitchhiker's guide, giving practical guidelines and references for each step of
      the typical lesion-behaviour mapping study pipeline.

PMID- 29066326
TI  - ERPs reveal perceptual and conceptual processing in 14-month-olds' observation of
      complete and incomplete action end-states.
AB  - Infants in the second year of life not only detect the visible goals or end
      states of other people's action, but they also seem to be able to infer others'
      underlying intentions. The present study used event-related potentials (ERPs) to
      investigate the biological basis of infants' processing of others' goal-directed
      actions, with special regard to the involvement of bottom-up perceptual and top
      down conceptual processes. In an adaptation of the behavioral re-enactment
      procedure, 14-month-olds were first familiarized with either full demonstrations
      (FD), failed attempts (FA), or arbitrary (AA) object-directed actions. Next, ERPs
      were measured while all infants saw the same two pictures of the end-states of
      the full demonstration (complete end-state) and the failed attempt (incomplete
      end-state). In the time-windows related to perceptual processing (100-200ms after
      stimulus onset) and to conceptual processing (300-700ms), ERP negativity over
      frontal and central regions was higher for the complete than for the incomplete
      end-state in the FD and FA conditions. When comparing the FA and AA conditions,
      this pattern of results occurred only for the conceptual time domain. Moreover,
      beginning slow-wave activity (700-1000ms) differed for the end-state pictures in
      the three conditions, suggesting differential encoding demands. Together, the
      electrophysiological data indicate that infants in the second year of life use
      bottom-up perceptual as well as top-down conceptual processing to give meaning to
      others' goal-directed actions.

PMID- 29066323
TI  - Correlation Between Incisional Biopsy Histological Subtype and a Mohs Surgery
      Specimen for Nonmelanoma Skin Cancer.
AB  - BACKGROUND: Histological diagnosis of a clinically suspected nonmelanoma skin
      cancer (NMSC) is recommended before treatment. For NMSC, concordance between the
      histological subtype of the preoperative biopsy and the excision specimen of
      basal cell carcinoma (BCC) has been reported to range from 10% to 81%. No large
      study on the concordance between NMSC histology seen in a preoperative biopsy
      with the following tumour specimen from Mohs micrographic surgery (MMS) has been
      performed in a Latin American population. OBJECTIVE: The aim of this study was to
      analyse and compare the histological subtype of the incisional biopsies reviewed
      by the dermatopathologist with the histological subtype of the tumour specimen
      obtained during MMS interpreted by the dermatopathologist and the Mohs surgeon.
      METHODS: A retrospective analysis of 320 NMSC was performed. The interobserver
      correlation was based on kappa values. RESULTS: The mean weighted kappa value
      between the preoperative NMSC biopsy and intraoperative histological subtype of
      the tumour specimen from MMS analysed by the Mohs surgeon and the
      dermatopathologist was 0.22 and 0.24, respectively. The correlation in the
      histologic subtype of the intraoperative tumour specimen from MMS that was
      interpreted by the dermatopathologist and Mohs surgeon was 0.58. CONCLUSIONS:
      Dermatologists need to be aware of the limited value of incisional biopsies to
      accurately diagnose the histological subtype of a NMSC. The concordance rate in
      the histological diagnosis of the tumour specimens that were obtained from MMS
      between the Mohs surgeon and the dermatopathologist is moderate. However, the
      correlation is low compared with incisional biopsy subtypes.

PMID- 29066324
TI  - Functional analysis by RNAi of an glutaredoxin gene in Helicoverpa armigera.
AB  - Glutaredoxins play crucial roles in maintaining intracellular redox homeostasis
      via scavenging of excess reactive oxygen species. In this study, a glutaredoxin
      domain-containing cysteine-rich gene from Helicoverpa armigera, named HaGdccr,
      was characterized. Sequence analysis revealed that it contains a glutaredoxin
      domain and a conserved cysteine and shares high sequence identity with other
      insect genes. HaGdccr mRNA expression was highest in molting larvae of the 3rd
      instar and was mainly detected in the central nervous system of larvae and the
      wings of adults. Quantitative real-time PCR results revealed that the expression
      of HaGdccr was suppressed at 1 and 6 h and increased at 24 h after the larvae
      were treated with 4  degrees C and hydrogen peroxide. When the larvae were
      exposed to 20  degrees C, HaGdccr decreased at 1 h and was induced at 12 and 24
      h. HaGdccr transcription level was downregulated at 2 and 12 h and upregulated at
      24 h after the adults were exposed to 0  degrees C. However, transcript levels
      were increased by high temperature in both larvae and adults. After knockdown of
      HaGdccr by RNA interference, the expression of antioxidant genes, including
      thioredoxin-like (Trx-like), catalase (CAT), glutathione-S-transferase (GST),
      thioredoxin reductase (TrxR), and thioredoxin (Trx), was increased, whereas that
      of thioredoxin peroxidase (Tpx) was decreased. In addition, we found that HaGdccr
      knockdown enhanced the enzymatic activity of superoxide dismutase and the
      contents of hydrogen peroxide and ascorbate. Taken together, these results
      indicate that HaGdccr may play significant roles in protecting organisms against
      oxidative damage.

PMID- 29066321
TI  - Macrophage polarization and allergic asthma.
AB  - Allergic asthma is associated with airway inflammation and airway
      hyperresponsiveness. Macrophage polarization has been shown to have a profound
      impact on asthma pathogenesis. On exposure to local microenvironments, recruited
      macrophages can be polarized into either classically activated (or M1) or
      alternatively activated (or M2) phenotypes. Macrophage polarization has been
      heavily associated with development of asthma. The process of regulation of
      macrophage polarization involves an intricate interplay between various
      cytokines, chemokines, transcriptional factors, and immune-regulatory cells.
      Different signals from the microenvironment are controlled by different receptors
      on the macrophages to initiate various macrophage polarization pathways. Most
      importantly, there is an increased attention on the epigenetic changes (eg,
      microRNAs, DNA methylation, and histone modification) that impact macrophage
      functional responses and M1/M2 polarization through modulating cellular signaling
      and signature gene expression. Thus, modulation of macrophage phenotypes through
      molecular intervention by targeting some of those potential macrophage regulators
      may have therapeutic potential in the treatment of allergic asthma and other
      allergic diseases. In this review, we will discuss the origin of macrophages,
      characterization of macrophages, macrophage polarization in asthma, and the
      underlying mechanisms regarding allergen-induced macrophage polarization with
      emphasis on the regulation of epigenetics, which will provide new insights into
      the therapeutic strategy for asthma.

PMID- 29066327
TI  - Genome and Methylome Variation in Helicobacter pylori With a cag Pathogenicity
      Island During Early Stages of Human Infection.
AB  - BACKGROUND & AIMS: Helicobacter pylori is remarkable for its genetic variation;
      yet, little is known about its genetic changes during early stages of human
      infection, as the bacteria adapt to their new environment. We analyzed genome and
      methylome variations in a fully virulent strain of H pylori during experimental
      infection. METHODS: We performed a randomized Phase I/II, observer-blind, placebo
      controlled study of 12 healthy, H pylori-negative adults in Germany from October
      2008 through March 2010. The volunteers were given a prophylactic vaccine
      candidate (n = 7) or placebo (n = 5) and then challenged with H pylori strain BCM
      300. Biopsy samples were collected and H pylori were isolated. Genomes of the
      challenge strain and 12 reisolates, obtained 12 weeks after (or in 1 case, 62
      weeks after) infection were sequenced by single-molecule, real-time technology,
      which, in parallel, permitted determination of genome-wide methylation patterns
      for all strains. Functional effects of genetic changes observed in H pylori
      strains during human infection were assessed by measuring release of interleukin
      8 from AGS cells (to detect cag pathogenicity island function), neutral red
      uptake (to detect vacuolating cytotoxin activity), and adhesion assays. RESULTS:
      The observed mutation rate was in agreement with rates previously determined from
      patients with chronic H pylori infections, without evidence of a mutation burst.
      A loss of cag pathogenicity island function was observed in 3 reisolates. In
      addition, 3 reisolates from the vaccine group acquired mutations in the
      vacuolating cytotoxin gene vacA, resulting in loss of vacuolization activity. We
      observed interstrain variation in methylomes due to phase variation in genes
      encoding methyltransferases. CONCLUSIONS: We analyzed adaptation of a fully
      virulent strain of H pylori to 12 different volunteers to obtain a robust
      estimate of the frequency of genetic and epigenetic changes in the absence of
      interstrain recombination. Our findings indicate that the large amount of genetic
      variation in H pylori poses a challenge to vaccine development.
      ClinicalTrials.gov no: NCT00736476.

PMID- 29066329
TI  - Midterm Angina-Related Quality of Life Benefits After Percutaneous Coronary
      Intervention of Chronic Total Occlusions.
AB  - BACKGROUND: Data on the impact of coronary chronic total occlusion (CTO)
      percutaneous coronary intervention (PCI) on quality of life (QOL) are limited. To
      date, studies have been limited in sample size and have focused on only a few
      domains of the Seattle Angina Questionnaire (SAQ). We evaluated the relationship
      between coronary CTO PCI and QOL in patients with symptoms of angina,
      incorporating all aspects of the SAQ. METHODS: The SAQ was used to interrogate
      patients at baseline and at 12 months after CTO PCI. The primary end point was
      improvement in SAQ scores. RESULTS: A total of 184 patients answered the baseline
      SAQ. One hundred twenty-two patients answered both questionnaires. SAQ responders
      were more likely to be men, more like to be in stable medical condition, and more
      likely to have undergone a successful procedure. We observed statistically
      significant improvement (P < 0.0001) in physical limitation (mean difference
      [MD], +27; 95% confidence interval [CI], +23 to +32), angina stability (MD, +16;
      95% CI, +10 to +21), angina frequency (MD, +27; 95% CI, +22 to +32), treatment
      satisfaction (MD, +10; 95% CI, +6 to +13), and QOL domains (MD, +28; 95% CI, +24
      to +32). Patients with coronary artery bypass grafting, dissection re-entry
      techniques, and high complexity (Japanese CTO [J-CTO] >= 3) had a similar degree
      of improvement when compared with their counterparts. CONCLUSIONS: CTO PCI is
      associated with a significant improvement in QOL at 12 months. Patients with
      complex CTOs derive benefits similar to those in patients with less complex CTOs.

PMID- 29066328
TI  - Synthesis of novel hybrid steroid dimers by BF3.Et2O-catalyzed aldol condensation
      of 2-formyl-estradiol diacetate and steroid sapogenins.
AB  - BF3.Et2O-catalyzed aldol condensation of steroid sapogenins with 2-formyl
      estradiol diacetate afforded two novel classes of steroid dimers in which an
      estrogenic core is attached to the spirostanic side chain of an steroid sapogenin
      through an exocyclic double bond in position C-23, or through a spiro centre in C
      22.

PMID- 29066331
TI  - Mitral Stenosis After Mitral Valve Repair for Degenerative Mitral Regurgitation
      Lessons Learned.

PMID- 29066330
TI  - Delayed Formation of a Massive Atrial Hematoma After Coronary Intervention
      Manifesting With an Isolated Cough: Multimodality Imaging and Outcome.
AB  - Coronary artery perforation is a relatively rare but potentially life-threatening
      complication of percutaneous coronary intervention because it could result in
      cardiac tamponade; exceptionally, distal coronary perforation could cause an
      acute formation of a mural hematoma, which could also prove lethal without
      adequate management. We report an exceptional case of a 76-year-old man in whom
      an important left atrial hematoma formed progressively over weeks after a planned
      percutaneous coronary intervention and manifested with an isolated cough.
      Diagnosis was made using multimodality imaging. A conservative strategy was
      adopted and produced a favourable outcome.

PMID- 29066332
TI  - Anticoagulation for Thromboembolic Risk Reduction in Adults With Congenital Heart
      Disease.
AB  - Adults with congenital heart disease (ACHD) represent one of the fastest
      expanding groups of patients in contemporary practice with unique and often
      complex management pathways. ACHD have a higher risk of thromboembolism not only
      from their complex physiology and anatomy but also from substrates such as
      valvular heart disease, atrial arrhythmias, cyanosis, and ventricular
      dysfunction, resulting in significant morbidity and mortality. Thromboembolic
      event rates in ACHD have been shown to be related to Congestive Heart Failure,
      Hypertension, Age (>=75 years), Diabetes, Stroke/Transient Ischemic Attack,
      Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) scores (0.75%,
      1.24%, and 2.65% per patient-year for CHA2DS2-VASc scores of 0, 1, and >= 2
      respectively), but are likely more strongly associated with disease complexity.
      However, optimum anticoagulation strategies have not been studied extensively in
      this group, mostly because of their heterogeneity and complex clinical profiles.
      Individual comorbidities, disease severity, and the presence of prosthetic
      material must be taken into consideration when determining the ideal
      anticoagulation strategy in pregnant patients. With improving survival and
      expanding treatment options, the requirement of thromboprophylaxis is steadily
      increasing, however, safety, choice, and duration of anticoagulation strategies
      in this group has not been well studied. In this review we aim to highlight the
      current understanding of antithrombotic therapy in the ACHD population, with
      discussion regarding special considerations in unique clinical situations
      relevant to ACHD.

PMID- 29066333
TI  - Qualitative review of usability problems in health information systems for
      radiology.
AB  - BACKGROUND: Radiology processes are commonly supported by Radiology Information
      System (RIS), Picture Archiving and Communication System (PACS) and other
      software for radiology. However, these information technologies can present
      usability problems that affect the performance of radiologists and physicians,
      especially considering the complexity of the tasks involved. OBJECTIVES: The
      purpose of this study was to extract, classify and analyze qualitatively the
      usability problems in PACS, RIS and other software for radiology. METHOD: A
      systematic review was performed to extract usability problems reported in
      empirical usability studies in the literature. The usability problems were
      categorized as violations of Nielsen and Molich's usability heuristics. RESULTS:
      The qualitative analysis indicated the causes and the effects of the identified
      usability problems. From the 431 papers initially identified, 10 met the study
      criteria. The analysis of the papers identified 90 instances of usability
      problems, classified into categories corresponding to established usability
      heuristics. The five heuristics with the highest number of instances of usability
      problems were "Flexibility and efficiency of use", "Consistency and standards",
      "Match between system and the real world", "Recognition rather than recall" and
      "Help and documentation", respectively. CONCLUSION: These problems can make the
      interaction time consuming, causing delays in tasks, dissatisfaction,
      frustration, preventing users from enjoying all the benefits and functionalities
      of the system, as well as leading to more errors and difficulties in carrying out
      clinical analyses. Furthermore, the present paper showed a lack of studies
      performed on systems for radiology, especially usability evaluations using formal
      methods of evaluation involving the final users.

PMID- 29066334
TI  - Making sense of SEND; the Standard for Exchange of Nonclinical Data.
AB  - The Standard for Exchange of Nonclinical Data (SEND) is currently the preferred
      submission format for nonclinical animal data by the US FDA and became a
      requirement on the 18th December 2016. Application of these data standards is the
      first step to being able to perform cross-study querying and is expected to open
      up opportunities for data mining and meta-analysis by the pharmaceutical
      industry. This paper reports on our experiences in developing a tool to allow
      recent SEND formatted studies to be explored alongside historical nonclinical
      data already gathered as part of the eTOX project. Combining SEND data with
      historical data will positively impact the power of any analysis performed and
      increase the likelihood of being able to detect rare effects. It describes the
      use of KNIME in generating dose group averages and incidences from individual
      animal level data captured in SEND. There are a number of options for opening and
      reading SEND files but the benefits of using KNIME are that it is a free, open
      source data mining framework which allows the data to be viewed in a holistic
      manner rather than one domain at a time. Additionally it incorporates several
      nodes useful for aggregating and visualising the data to more easily identify
      patterns and trends.

PMID- 29066335
TI  - Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve,
      45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated
      intravenous administration.
AB  - The selection of a suitable vehicle for administration of NCEs in non-clinical
      studies is always a challenge for poorly soluble compounds. Challenge is
      increased if the dose formulation is intended for intravenous (i.v.)
      administration where isotonic, biologically compatible pH and solution form is an
      absolute requirement. Vehicle toxicity and tolerability data are not readily
      available for a number of combination vehicles therefore, an i.v. tolerability
      studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene
      glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume
      of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was
      administered via lateral tail vein and effects on clinical signs, body weights,
      feed consumption, clinical pathology and histopathology were evaluated. Clinical
      signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg
      during the course of the study. At 2 mL/kg, injection site injury without
      systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of
      5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to
      28 days without any discomfort or injury to rats.

PMID- 29066336
TI  - Safety investigation on total steroid saponins extracts from Dioscorea
      zingiberensis C.H. Wright: Sub-acute and chronic toxicity studies on dogs.
AB  - Sub-acute and chronic toxic effects of total steroidal saponins (TSSN) extracts
      from Dioscorea zingiberensis C.H. Wright on various internal organs and
      biochemical indicators have never been studied before and this study is the first
      of its kind to demonstrate sub-acute and chronic toxicities of TSSN on dogs.
      Administration of TSSN extracts at doses up to 3000 mg/Kg daily for 14 days, no
      biochemical and organ changes were observed on the experimental groups of dogs.
      Further, chronic toxicity study through oral administration of TSSN extracts at
      the gradual doses of 50, 250 and 500 mg/Kg for 90 days followed by a 2-week
      recovery assay revealed absence of significant architectural and morphological
      changes in internal organs which were confirmed through histopathological
      examination and merely no significant alteration in the biochemical indicators
      including hematologic and urine analysis and electrocardiogram compared to the
      control dogs. This toxicological evaluation came across with the finding that the
      herbal preparation can be considered as nontoxic and animals could tolerate the
      extracts at doses up to 500 mg/Kg with LD50 greater than 3000 mg/Kg. It may serve
      as a preliminary scientific evidence for further therapeutic investigations.

PMID- 29066337
TI  - Clostridium difficile causing pediatric infections: New findings from a hospital
      based study in Italy.
AB  - Recent studies support a change of Clostridium difficile infections (CDIs)
      epidemiology in pediatric patients. Since limited information is available about
      C. difficile in this population, we investigated the epidemiology of CDI in a
      large pediatric hospital that acts as reference centre in Italy and analyzed C.
      difficile isolates to identify the prevalent PCR-ribotypes (RTs), the binary
      toxin (CDT)-positive strains and the antibiotic susceptibility patterns. The CDI
      incidence was 6.6 cases/1000 admissions and the majority (92%) of CDI were
      healthcare-associated (47% occurred in the Hematology-Oncology and in the
      Gastroenterology units). Most of symptomatic children <3 years with a positive
      culture for C. difficile were negative for other gastrointestinal pathogens,
      supporting C. difficile as cause of disease in these patients, including those
      showing recurrences. Strains RT020 (16%) and RT014 (14%) were identified as the
      main cause of infection, while RT356/607 and RT018, predominant in Italian adult
      patients, were absent (RT356/607) or rarely found (RT018) among children. CDT
      positive strains represented the 20% of the total number of isolates analyzed. In
      particular, two emerging types, RT033 and RT442, were recognized as Toxin A
      /Toxin B-/CDT+. Resistance to antibiotics characterized almost 50% of the
      toxigenic isolates analyzed in this study and, in particular, 20% of them were
      multidrug resistant (MDR). The emergence and circulation of strains with peculiar
      toxins profiles and/or MDR strongly highlight the necessity of a rapid CDI
      diagnosis, a careful monitoring of C. difficile in pediatric patients and a more
      strict control of antibiotics usage in the Italian pediatric hospitals.

PMID- 29066338
TI  - Electrocardiographic changes after successful recanalization of a chronic total
      coronary occlusion. A systematic review and meta-analysis.
AB  - BACKGROUND: Observational studies suggest that in patients with a CTO successful
      recanalization is associated with better clinical outcome. This could be related
      to a reduction in the occurrence of arrhythmias, which may result from
      modifications of the hibernating myocardium in a CTO region. METHODS AND RESULTS:
      We aimed to evaluate the effect of CTO PCI on electrophysiological parameters,
      and conducted a systematic review and meta-analysis according to the PRISMA
      guidelines. MEDLINE and EMBASE were searched. Titles and abstracts identified by
      the search strategy were independently screened by two investigators. Data were
      extracted and used for meta-analyses where possible. In total, eight studies
      incorporating 467 patients were included in this review, evaluating the effect of
      successful CTO PCI on various ECG parameters. Three studies showed a significant
      decrease in mean QT dispersion of 17.46ms [95% CI 10.62-24.30] after successful
      CTO PCI. QTc dispersion also decreased significantly, with a mean decrease of
      18.74ms [95% CI 11.53-25.94]. In one trial a significant decrease in Tp-e
      interval in leads V2 and V5, and a significant decrease in Tp-e/QT ratio in leads
      V2 and V5 post-CTO PCI were observed. CONCLUSIONS: This first systematic review
      and meta-analysis suggests that successful CTO PCI is associated with an
      immediate decrease in ECG parameters that reflect heterogeneity in depolarization
      and repolarization, which could lead to a reduction in the risk for ventricular
      arrhythmias and sudden cardiac death. We raise the hypothesis that hibernating
      myocardium in a CTO region may not be as deeply "in sleep" as one would assume.

PMID- 29066339
TI  - Long-term invasive follow-up of bioresorbable vascular scaffold: Optical
      Coherence Tomography assessment of jailed side branches.
AB  - BACKGROUND: Little is known about the long term development of the tissue bridges
      covering the struts of bioresorbable vascular scaffold (BVS) at the side branches
      (SB) ostium. This study aims at assessing the resorption process of jailed SB
      after BVS implantation. METHODS: We performed both Optical Coherence Tomography
      (OCT) and Intravascular Ultrasound (IVUS) analysis of 7 patients enrolled in the
      ABSORB Cohort B trial at our center. Orifice SB area and mean thickness of tissue
      bridge covering SB were calculated from 2D assessment. The number of SB orifice
      compartments separated by BRS struts was analysed by using 3D OCT reconstruction.
      RESULTS: At 5years follow-up, no struts could be identified. Between 3 and
      5years, both lesion-level and cross section-level OCT findings showed a
      significant increase in Mean lumen area (MLA) (4.67+/-1.66mm2 vs. 5.57+/-1.57mm2;
      p=0.04) as well as Minimum Lumen Area (MinLA) (5.98+/-1.98mm2 vs. 6.73+/-1.87mm2;
      p=0.04). Moreover, eccentricity index showed a significant reduction between 3
      and 5years (0.28+/-0.35mm2 vs. 0.16+/-0.06mm2; p=0.04). We identified a total of
      3 SBs ostia in the segments treated with BVS. Between 3 and 5years follow-up in
      all SB analysed, we detected a decrease of mean tissue bridge thickness and an
      increase of calculated SBs area. CONCLUSIONS: In our serial OCT, a significant
      decrease of tissue bridge formation together with SB orifice area enlargement
      from 3 to 5year follow-up has been proved.

PMID- 29066340
TI  - Drug eluting balloon for the treatment of patients with coronary artery disease:
      Current perspectives.
AB  - Despite the improvement of outcomes after the introduction of bare metal and drug
      eluting stents for the treatment of CAD, certain type of patients have still an
      increased risk of stent failure. An alternative is represented by drug-eluting
      balloons (DEB). This innovation could give potential benefits in particular for
      the in-stent restenosis (ISR) and the de-novo lesions. In the first setting DEB
      have shown results superior to those with plain-balloon angioplasty and similar
      to those with first generation DES. Their performance seems to be more evident in
      BMS-ISR than in DES-ISR, showing a reliable effectiveness in those cases of
      recalcitrant ISR or when dual antiplatelet therapy is not indicated. In the
      context of de-novo lesions the use of DEB as unique strategy results more safe
      and feasible than a strategy with combined BMS implantation. The results are
      comparable to DES in lesions limited to small coronary vessels. Other particular
      scenarios, like bifurcations, acute myocardial infarction and diffuse disease,
      have been approached with DEB resulting in very heterogeneous outcomes. At
      present, given the high efficacy of last generation DESs, DEBs should be
      considered where clinical and angiographic conditions require the avoidance of
      stent implantation.

PMID- 29066341
TI  - Full stent expansion of chronic total occlusion lesions requires prolonged
      inflation.
AB  - : Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has been
      associated in some studies with higher target vessel revascularization (TVR)
      rates than non-CTO PCI. Optimal stent inflation time and its effect on TVR in CTO
      PCI is unknown. We investigated the time required for stent deployment using the
      previously described pressure optimized protocol (POP), which uses stent balloon
      pressure stability rather than an arbitrary inflation time as an end point for
      balloon deflation. We also compared TVR with CTO PCI vs non-CTO using the POP
      protocol in both groups. METHODS: Patients with successful CTO PCI using POP
      between 2012 and 2015 were included. Patients having non-CTO PCI using POP and
      matched for stent diameter and length and temporal proximity constituted the
      control group to compare inflation time (n=83 each). TVR at 1year was compared
      between PCI during the time period using POP (CTO=83, non-CTO=263). RESULTS:
      Stent inflation time to achieve optimal stent inflation using POP was longer in
      CTO vs non-CTO lesions (136+/-60 vs 108+/-51s, p=0.001). TVR at 365days was
      similar in CTO and non-CTO cohorts (2.4% vs 2.6%, p=0.9). CONCLUSION: Stent
      expansion using POP in CTO lesions requires longer inflation duration but leads
      to similar TVR rates at 1year in CTO PCI compared with non-CTO PCI.

PMID- 29066342
TI  - Bioprosthesis leaflet thrombosis following self-expanding valve-in-valve
      transcatheter aortic valve replacement in patient taking factor Xa inhibitor and
      warfarin: A case report.
AB  - An 87-year-old female with symptomatic severe aortic stenosis underwent
      transcatheter valve replacement (TAVR) via the transfemoral approach with a 29mm
      self-expanding device. Moderate to severe paravalvular regurgitation led to the
      development of congestive heart failure and hospital readmission 1 month
      following TAVR. A second 29mm valve was placed to abolish the paravalvular
      regurgitation. Routine follow-up computed tomography (CT) imaging demonstrated
      leaflet thickening and decreased leaflet mobility suggesting valve thrombosis,
      despite adherence to Factor Xa inhibitor. Transthoracic echocardiogram revealed
      normal transaortic valve gradients. The patient was transitioned to a vitamin K
      antagonist and repeat imaging 3months later demonstrated progression of
      thrombosis to an additional leaflet. The case illustrates the potential increased
      risk of leaflet thrombosis in patients receiving valve-in-valve TAVR procedures,
      the superiority of multidetector computed tomography to image subclinical leaflet
      thrombosis, and highlights the need for further investigation in this area.

PMID- 29066343
TI  - Intravascular ultrasound assessment of minimum lumen area and intimal hyperplasia
      in in-stent restenosis after drug-eluting or bare-metal stent implantation. The
      Nordic Intravascular Ultrasound Study (NIVUS).
AB  - INTRODUCTION: Drug-eluting stents (DES) reduce the risk of restenosis after
      percutaneous coronary intervention. The aim of the study was to evaluate, by
      intravascular ultrasound (IVUS), the minimum lumen area site in the stented
      segment and the distribution of intimal hyperplasia in patients presenting with a
      DES or bare-metal stent (BMS) in-stent restenosis. METHODS: The "Nordic
      Intravascular Ultrasound Study (NIVUS)" study was conducted in Nordic and Baltic
      countries as a prospective multicenter registry. Two hundred nine patients (DES
      n=121 and BMS n=88) with in-stent restenosis were enrolled. RESULTS: At the
      minimum lumen area site in the stented segment, the stent area (5.8+/-2.2mm2 vs.
      7.6+/-2.4mm2, p<0.001) and intimal hyperplasia area (2.6+/-2.0mm2 vs. 5.0+/
      2.2mm2, p<0.001) were significantly lower in patients treated with DES compared
      to BMS. The percentage of stents that did not have a minimum stent area of at
      least 5.0mm2 (under expansion) was higher in DES (58.7% vs. 37.7%, p=0.008)
      compared to BMS. Intimal hyperplasia covered 55.4+/-33.3% of the stent length in
      the DES compared to 90.7+/-17.4% in the BMS group, p<0.001. Focal in-stent
      restenosis was more often seen in DES treated patients compared to BMS treated
      patients (DES n=84 (59.9%) vs. BMS n=15 (17.0%), p<0.001). CONCLUSION: Stent
      underexpansion was more often seen in DES than BMS in-stent restenosis. DES more
      often had focal in-stent restenosis with less intimal hyperplasia.

PMID- 29066345
TI  - Sequence conservation of protein binding segments in intrinsically disordered
      regions.
AB  - Intrinsically disordered proteins are proteins with intrinsically disordered
      regions (IDRs) that do not adopt a globular structure in their free state. IDRs
      have unique regions having protein-binding segments of which play pivotal roles
      in many biological processes. The binding sites in IDRs are heterogeneous in
      terms of their sequence conservation: some are conserved and others are not. We
      have been running a database of intrinsically disordered proteins, IDEAL, and
      collecting such binding segments, which are called protean segments (ProSs),
      within it. In this study, we compared the sequence conservation of ProSs,
      structural domains (SDs), and IDRs other than ProSs (non-ProSs) and found that i)
      functionally constrained residues in ProSs tend to be conserved, ii) the
      distribution of conservation scores of ProSs is similar to those of SDs but not
      non-ProSs, and iii) ProSs found in human proteins are mostly conserved only in
      vertebrates. These results indicate that the conservation patterns in ProSs
      principally follow the general rules found in SDs. However, we need to consider
      evolutionary distance when comparing IDR sequences because ProSs can readily
      emerge and disappear over the course of protein evolution. Moreover, many ProSs
      may remain to be identified, which may account for the heterogeneity of the
      sequence conservation of IDRs.

PMID- 29066344
TI  - Uncontrolled eating in adolescents: The role of impulsivity and automatic
      approach bias for food.
AB  - Obesity is a global problem reaching epidemic proportions and can be explained by
      unhealthy eating and sedentary lifestyles. Understanding the psychological
      processes underlying unhealthy eating behaviour is crucial for the development of
      effective obesity prevention programmes. Dual-process models implicate the
      interplay between impaired cognitive control and enhanced automatic responsivity
      to rewarding food cues as key risk factors. The current study assessed the
      influence of four different components of trait impulsivity (reflecting impaired
      cognitive control) and automatic approach bias for food (reflecting automatic
      responsivity to food) on uncontrolled eating in a large sample (N = 504) of young
      adolescents. Of the four impulsivity factors, negative urgency was found to be
      the strongest predictor of uncontrolled eating. Interestingly, we found that lack
      of premeditation was a key risk factor for uncontrolled eating, but only when
      approach bias for food was high, supporting a dual-process model. Lack of
      perseverance showed a similar interactive pattern to a lesser degree and
      sensation-seeking did not predict uncontrolled eating. Together, our results show
      that distinct components of trait impulsivity are differentially associated with
      uncontrolled eating behaviour in adolescents, and that automatic processing of
      food cues may be an important factor in modulating this relationship.

PMID- 29066346
TI  - Characterization of overexpression of the alternatively spliced isoform of the
      protein phosphatase 2A catalytic subunit in cells.
AB  - PP2Acalpha2 is a recently discovered PP2Acalpha alternative splicing isoform that
      can be induced following serum withdrawal. It shows enhanced binding to
      immunoglobulin binding protein 1 and is overexpressed in chronic lymphocytic
      leukemia patients. Current knowledge concerning PP2Acalpha2 is limited. In this
      study, we induced and cloned PP2Acalpha2 from HL-60 cells and human lymphocytes,
      transfected them into human embryonic kidney 293 cells and constructed a stable
      overexpression cell line. We found that PP2Acalpha2 mRNA inhibits expression of
      its longer isoform PP2Acalpha mRNA but had no effect on the final protein
      expression and modification of this longer isoform. Moreover, PP2Acalpha2
      overexpressed cells demonstrated increased expression of IGBP1, activated mTORC1
      signaling to reduce basal autophagy and increased anchorage-independent growth.
      Our study provides new insights into the complex mechanisms of PP2A regulation.

PMID- 29066347
TI  - JAK2V617F influences epigenomic changes in myeloproliferative neoplasms.
AB  - Negative valine (V) to phenylalanine (F) switch at the Janus kinase (JAK2) 617
      codon (V617F) is the dominant driver mutation in patients with myeloproliferative
      neoplasms (MPNs). JAK2V617F was proved to be sufficient for cell transformation;
      however, independent mutations might influence the following epigenomic
      modifications. To assess the JAK2V617F-induced downstream epigenomic changes
      without interferences, we profiled the epigenomic changes in ectopically
      expressed JAK2V617F in Ba/F3 cells. Antibodies against phosphorylated signal
      transducer and activator of transcription 3 (pSTAT3) and enhancer of zeste
      homolog 2 (EZH2) were used for chromatin-immunoprecipitation sequencing (ChIP
      seq) to detect the downstream epigenomic targets in the JAK2-STAT3 signaling
      pathway. To confirm the JAK2V617F-induced epigenetic changes in vivo, DNA
      methylation changes in the target loci in patients with MPNs were detected
      through methylation-specific polymerase chain reaction and were clustered against
      the changes within controls. We found that ectopically expressed JAK2V617F in
      Ba/F3 cells reduced the binding specificity; it was associated with cis
      regulatory elements and recognized DNA motifs in both pSTAT3-downstream and EZH2
      associated targets. Overlapping target loci between the control and JAK2V617F
      were <3% and 0.4%, respectively, as identified through pSTAT3 and EZH2 ChIP-seq.
      Furthermore, the methylation changes in the direct target loci (FOXH1, HOXC9, and
      SRF) were clustered independently from the control locus (L1TD1) and other
      mutation genes (HMGA2 and Lin28A) in the analyzed MPN samples. Therefore,
      JAK2V617F influences target binding in both pSTAT3 and EZH2. Without mutations in
      epigenetic regulators, JAK2V617F can induce downstream epigenomic modifications.
      Thus, epigenetic changes in JAK2 downstream targets might be trackable in vivo.

PMID- 29066348
TI  - A chemical screen identifies trifluoperazine as an inhibitor of glioblastoma
      growth.
AB  - Glioblastoma (GBM) is regarded as the most common malignant brain tumor but
      treatment options are limited. Thus, there is an unmet clinical need for
      compounds and corresponding targets that could inhibit GBM growth. We screened a
      library of 80 dopaminergic ligands with the aim of identifying compounds capable
      of inhibiting GBM cell line proliferation and survival. Out of 45 active
      compounds, 8 were further validated. We found that the dopamine receptor D2
      antagonist trifluoperazine 2HCl inhibits growth and proliferation of GBM cells in
      a dose dependent manner. Trifluoperazine's inhibition of GBM cells is cell line
      dependent and correlates with variations in dopamine receptor expression profile.
      We conclude that components of the dopamine receptor signaling pathways are
      potential targets for pharmacological interventions of GBM growth.

PMID- 29066349
TI  - Dihydroceramide is a key metabolite that regulates autophagy and promotes
      fibrosis in hepatic steatosis model.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an increasingly common chronic liver
      disease worldwide. Sphingolipids are a family of lipids that play essential roles
      as critical regulators in metabolic disorders. Some sphingolipids are known key
      factors in metabolic dysfunction. However, the precise effect of dihydroceramide
      on NAFLD remains unknown. Here, we report how dihydroceramide in autophagosome
      accumulation activates fibrogenesis in human liver Chang cells treated with free
      fatty acids (FFA). According to LC/MS lipid profiling, FFA increased the levels
      of sphingolipids and triacylglycerol (TG). To demonstrate the potential role of
      dihydroceramide metabolism in autophagy, several sphingolipid synthesis
      inhibitors were used. Increased dihydroceramide led to impairment of autophagic
      flux, resulting in increased TG storage in lipid droplets (LD) and upregulated
      expression of fibrosis markers. Hepatic stellate cells (HSCs, LX-2 cells) were co
      cultured with Chang cells to assess the potential fibrogenic response to
      dihydroceramide, Treatment with rapamycin recovered autophagic flux in Chang
      cells and fibrogenesis in the co-culture system. Our results identified a
      critical function of dihydroceramide metabolism in autophagy. It could play an
      important role in the progression of NAFLD associated with lipid over
      accumulation. Therefore, preventing autophagic flux by regulating dihydroceramide
      could be a potential strategic approach for providing therapy for NAFLD.

PMID- 29066351
TI  - The downregulation of miR-3173 in B-cell acute lymphoblastic leukaemia promotes
      cell invasion via PTK2.
AB  - MicroRNAs are important regulators of the pathogenesis of B-cell acute
      lymphoblastic leukaemia (B-ALL). In this study, we identified miR-3173 and its
      predicted target gene PTK2 were correspondingly differentially expressed in B-ALL
      patients. In B-ALL cell lines, CCK-8 proliferation assay revealed that miR-3173
      could inhibit the cell proliferation. Moreover, transwell assay revealed that miR
      3173 could also inhibit cell migration and invasion in B-ALL cell lines.
      Luciferase assays revealed that miR-3173 directly bound to the 3'untranslated
      region of PTK2, and western blotting showed that miR-3173 suppressed the
      expression of PTK2 at the protein level. Generally, this study indicates that miR
      3173 negatively regulates PTK2 and inhibits proliferation and invasion of B-ALL
      cell lines. Thus, miR-3173 may represent a potential therapeutic molecule for B
      ALL intervention.

PMID- 29066350
TI  - Downregulation of ZMYND11 induced by miR-196a-5p promotes the progression and
      growth of GBM.
AB  - ZMYND11 (zinc finger MYND-type containing 11) has been widely regarded to be
      involved in a variety of cancers as a potential suppressor. However, the
      biological role and mechanism of ZMYND11 in glioblastoma multiform (GBM) remain
      unknown. In this study, we found that ZMYND11 expression was remarkably decreased
      in GBM tissues from 20 cases and cell line (U87) compared to normal brain tissue
      from 10 cases (P < 0.001). Furthermore, we explored that ZMYND11 upregulation
      significantly suppressed U87 cells proliferation and invasion, induced cell cycle
      arrest and apoptosis in vitro. Subsequently, we identified increased ZMYND11
      inhibited the tumor growth using tumor cells xenograft experiment on rude mice.
      Moreover, we explored that ZMYND11 was a new direct and functional target of miR
      196a-5p in U87 via luciferase reporter assay. In addition, we confirmed the
      negative correlation between miR-196a-5p and ZMYND11 in GBM tissue and U87 cells
      by changing the expression level of miR-196a-5p with lentivirus and plasmid
      vector. Furthermore, we demonstrated that decreased ZMYND11 could reverse
      suppressive effect of downregulated miR-196a-5p on U87 by rescue experiment.
      Taken together, ZMYND11 was demonstrated to be a potential and extremely
      promising suppressor of GBM, while miRNA-196a-5p was quite an important target of
      treatment of GBM.

PMID- 29066352
TI  - Loss of Ribosomal Protein L24A (RPL24A) suppresses proline accumulation of
      Arabidopsis thaliana ring zinc finger 1 (atrzf1) mutant in response to osmotic
      stress.
AB  - Proline (Pro) metabolism in plants is involved in various cellular processes
      mediated during abiotic stress. However, the Pro-regulatory mechanisms are
      unclear. We used a suppressor mutation technique to isolate novel genes involved
      in the regulation of Pro metabolism in Arabidopsis. Using atrzf1 as a parental
      plant for T-DNA tagging mutagenesis, we identified a suppressor mutant, termed
      proline content alterative 21 (pca21), that displayed reduced Pro contents
      compared with the atrzf1 under osmotic stress conditions. Genomic Thermal
      Asymmetric Interlaced (TAIL)-PCR revealed pca21 harbored an inserted T-DNA in the
      region of At2g36620 that encodes Ribosomal Protein L24A. In general, the pca21
      mutant partially suppressed the insensitivity of atrzf1 to osmotic stress and
      abscisic acid during seed germination and early seedling stage. Additionally, the
      pca21 mutant had increased MDA content and lower expression of several Pro
      biosynthesis-related genes than the atrzf1 mutant during drought condition. These
      results suggest that pca21 acts as partial suppressor of atrzf1 in the osmotic
      stress response through the Pro-mediated pathway.

PMID- 29066353
TI  - Generalized concentration addition accurately predicts estrogenic potentials of
      mixtures and environmental samples containing partial agonists.
AB  - Cell-based bioanalytical tools are considered one alternative to overcome
      limitations of sensitivities of instrumental, analytical chemistry for monitoring
      estrogenic chemicals in the environment. Because these tools also reflect non
      additive interactions of chemicals in mixtures, their outcomes often deviate from
      outcomes of chemical analytical approaches that assume additivity, e.g. the
      concentration addition (CA) model. Often this is because CA is unable to
      adequately represent effects of partial agonists, i.e. estrogens with lesser
      efficacies compared to 17beta-estradiol. A generalized concentration addition
      (GCA) model has been proposed to address this shortcoming. In the present study,
      we investigated effects of mixtures of isomers of nonylphenol as partial model
      agonists in a cell-based estrogenicity assay. Whether the GCA model was able to
      more accurately predict the outcomes of these and previously published mixture
      experiments was evaluated, as well as the potency of a set of comprehensively
      characterized sewage effluent samples, compared to CA. If samples contained
      partial agonists, the GCA model consistently predicted potencies of mixtures and
      extracts of environmental samples more accurately than did the CA model. These
      findings enable more accurate estimations of potencies of estrogenicity explained
      by concentrations of agonists and partial agonists, thus significantly improving
      the ability to identify causative chemicals.

PMID- 29066354
TI  - Molecular mechanism of action of oxazolinoanthracyclines in cells derived from
      human solid tumors. Part 2.
AB  - BACKGROUND/AIM: Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU)
      are derivatives of anthracyclines (DOX and DAU) with a modified daunosamine
      moiety. We aimed to clarify their mechanisms of action by investigating
      intracellular accumulation and effects on the cell cycle, phosphatidylserine
      externalization, and proteasome 20S activity. MATERIALS AND METHODS: Experimental
      model consisted of SKOV-3, A549 and HepG2 cells. Compounds were used at the
      concentration of 80nM. Intracellular accumulation, drug uptake, and proteasome
      20S activity were evaluated by fluorimetric methods. The effects on the cell
      cycle and phosphatidylserine externalization were measured by flow cytometry.
      RESULTS: O-DOX was equivalent to DOX in terms of inducing G2/M arrest, but O-DAU
      was less potent in SKOV-3, HepG2, and A549 cells. O-DOX had the greatest effect
      on initiating apoptosis in all tested cells. Externalization of
      phosphatidylserine was significantly higher following O-DOX treatment compared
      with control cells and cells incubated with DOX. The intracellular accumulation
      and uptake of the derivatives were similar to those of the reference drugs.
      Tested compounds are able to activate proteasome 20S activity. CONCLUSION: Our
      results extended the understanding of the toxicity, mechanism of action, and
      biochemical properties of oxazoline derivatives of doxorubicin and daunorubicin,
      including their effects on cell cycle, apoptosis and DNA degradation.

PMID- 29066356
TI  - Structural Insights into the Substrate Recognition Mechanism of Arabidopsis GPP
      Bound NUDX1 for Noncanonical Monoterpene Biosynthesis.

PMID- 29066355
TI  - Response to correction of refractive errors and hypoaccommodation in children
      with congenital Zika syndrome.
AB  - PURPOSE: To describe the immediate response to correction of refractive errors
      and hypoaccommodation in children with congenital Zika syndrome (CZS). METHODS:
      Children born between May and December 2015 with a confirmed diagnosis of CZS and
      enrolled in a multidisciplinary early intervention program were included in this
      study. All children received a comprehensive ophthalmic examination, including
      dynamic retinoscopy and cycloplegic refraction. Children were prescribed their
      full correction if they met the criteria for refractive error, and additional
      plus 3.00 overcorrection for strabismus, accommodative dysfunction, and/or low
      vision. Monocular and binocular visual responses to Lea Grating Test at 30 cm,
      with and without eyeglasses, were measured on day 1 of glasses wear. RESULTS: A
      total of 60 children were evaluated (mean age at evaluation, 11.5 +/- 1.1 months;
      range, 9.0-16.0 months). Lea Grating Test responses were abnormal in all children
      prior to spectacle correction. Hypoaccommodation was present in 17 of 21 children
      (81%). Overcorrection was prescribed for all children. Visual responses were
      subnormal even with glasses use; however, immediate improvement in binocular
      vision was found in 37 children (62%) and in 74 of 119 eyes (62.2%). For the
      monocular visual improvement, 27 of 115 eyes (23.5%) had structural
      abnormalities, and 44 of 115 eyes (38.3%) were structurally normal. There was a
      statistical difference between the cycloplegic refraction of the children in
      August and in November, including emmetropia (P = 0.001), hyperopia (P = 0.000),
      myopia (P = 0.007), and astigmatism (P = 0.004). CONCLUSIONS: Eyeglasses can
      improve visual acuity in children with CZS. Significant changes in their
      refractive status over time requires periodic updates.

PMID- 29066357
TI  - Barley Stripe Mosaic Virus gammab Interacts with Glycolate Oxidase and Inhibits
      Peroxisomal ROS Production to Facilitate Virus Infection.

PMID- 29066358
TI  - The bioengineering of stem cells to create dopamine replacement neurons is not
      the solution for Parkinson's.

PMID- 29066360
TI  - Early Detection of Ureteropelvic Junction Obstruction Using Signal Analysis and
      Machine Learning: A Dynamic Solution to a Dynamic Problem.
AB  - PURPOSE: We sought to define features that describe the dynamic information in
      diuresis renograms for the early detection of clinically significant
      hydronephrosis caused by ureteropelvic junction obstruction. MATERIALS AND
      METHODS: We studied the diuresis renogram of 55 patients with a mean +/- SD age
      of 75 +/- 66 days who had congenital hydronephrosis at initial presentation. Five
      patients had bilaterally affected kidneys for a total of 60 diuresis renograms.
      Surgery was performed on 35 kidneys. We extracted 45 features based on curve
      shape and wavelet analysis from the drainage curves recorded after furosemide
      administration. The optimal features were selected as the combination that
      maximized the ROC AUC obtained from a linear support vector machine classifier
      trained to classify patients as with or without obstruction. Using these optimal
      features we performed leave 1 out cross validation to estimate the accuracy,
      sensitivity and specificity of our framework. Results were compared to those
      obtained using post-diuresis drainage half-time and the percent of clearance
      after 30 minutes. RESULTS: Our framework had 93% accuracy, including 91%
      sensitivity and 96% specificity, to predict surgical cases. This was a
      significant improvement over the same accuracy of 82%, including 71% sensitivity
      and 96% specificity obtained from half-time and 30-minute clearance using the
      optimal thresholds of 24.57 minutes and 55.77%, respectively. CONCLUSIONS: Our
      machine learning framework significantly improved the diagnostic accuracy of
      clinically significant hydronephrosis compared to half-time and 30-minute
      clearance. This aids in the clinical decision making process by offering a tool
      for earlier detection of severe cases and it has the potential to reduce the
      number of diuresis renograms required for diagnosis.

PMID- 29066361
TI  - Science Mandates Precision: A Plea for Accuracy in Reporting.

PMID- 29066359
TI  - Postimplantation Mga expression and embryonic lethality of two gene-trap alleles.
AB  - BACKGROUND: The dual-specificity T-box/basic helix-loop-helix leucine zipper
      transcription factor MGA is part of the MAX-interacting network of proteins. In
      the mouse, MGA is necessary for the survival of the pluripotent epiblast cells of
      the peri-implantation embryo and a null, gene-trap allele MgaGt results in
      embryonic lethality shortly after implantation. We have used this allele to
      document expression of Mga in postimplantation embryos and also investigated a
      second, hypomorphic gene-trap allele, MgaInv. RESULTS: Compound heterozygotes,
      MgaGt/MgaInv, die prior to midgestation. The extraembryonic portion of the
      embryos appears to develop relatively normally while the embryonic portion,
      including the pluripotent cells of the epiblast, is severely retarded by E7.5.
      Mga expression is initially limited to the pluripotent inner cell mass of the
      blastocyst and epiblast, but during organogenesis it is widely expressed, notably
      in the central nervous system and sensory organs, reproductive and excretory
      systems, heart, somites and limbs. CONCLUSIONS: Widespread yet specific areas of
      expression of Mga during organogenesis raise the possibility that the
      transcription factor may play roles in controlling proliferation and potency in
      the progenitor cell populations of different organ systems. Documentation of
      these patterns sets the stage for the investigation of specific progenitor cell
      types.

PMID- 29066362
TI  - Cross-Sectional Epidemiological Analysis of the Nagahama Study for Correlates of
      Overactive Bladder: Genetic and Environmental Considerations.
AB  - PURPOSE: The prevalence of overactive bladder is increasing globally. It has a
      substantial impact on quality of life and represents a heavy economic burden. We
      evaluated the prevalence of overactive bladder in a Japanese population and
      analyzed whether genetic and environmental factors influence overactive bladder.
      MATERIALS AND METHODS: This cross-sectional study was performed as part of the
      Nagahama cohort project. It comprised a questionnaire survey as well as
      anthropometric, physiological and biochemical measures, and genomic information
      on participants 30 to 74 years old in Nagahama, Japan. A genome-wide association
      study was performed in 4,645 participants, including 1,521 men and 3,124 women,
      using 99,059 single nucleotide polymorphisms. Univariate and multivariable
      logistic regression was done to analyze environmental factors associated with
      overactive bladder. RESULTS: The prevalence of overactive bladder was 11.8%,
      including 15.3% in men and 10.1% in women, and it increased with age. We found no
      significant association between overactive bladder and any single nucleotide
      polymorphism in the genome-wide association study. However, in the multivariable
      logistic regression model overactive bladder was positively associated with
      environmental factors, including age, depression and the consumption of cake or
      Japanese confection. CONCLUSIONS: The prevalence of overactive bladder was
      greater in men than in women, especially among the elderly. Environmental factors
      rather than genetic variants more likely contribute to overactive bladder.

PMID- 29066363
TI  - Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney
      Cancer: Results from a Multicenter Confirmatory Study.
AB  - PURPOSE: We sought to confirm the findings from a previous single institution
      study of 572 patients from Memorial Sloan Kettering Cancer Center in which we
      found that 49% of patients recovered to the preoperative estimated glomerular
      filtration rate within 2 years following radical nephrectomy for renal cell
      carcinoma. MATERIALS AND METHODS: A multicenter retrospective study was performed
      in 1,928 patients using data contributed from 3 independent centers. The outcome
      of interest was postoperative recovery to the preoperative estimated glomerular
      filtration rate. Data were analyzed using cumulative incidence and competing
      risks regression with death from any cause treated as a competing event. RESULTS:
      This study demonstrated that 45% of patients had recovered to the preoperative
      estimated glomerular filtration rate by 2 years following radical nephrectomy.
      Furthermore, this study confirmed that recovery of renal function differed
      according to preoperative renal function such that patients with a lower
      preoperative estimated glomerular filtration rate had an increased chance of
      recovery. This study also suggested that larger tumor size and female gender were
      significantly associated with an increased chance of renal function recovery.
      CONCLUSIONS: In this multicenter retrospective study we confirmed that in the
      long term a large proportion of patients recover to preoperative renal function
      following radical nephrectomy for kidney tumors. Recovery is more likely among
      those with a lower preoperative estimated glomerular filtration rate.

PMID- 29066364
TI  - Evidence for molecular antagonistic mechanism between mercury and selenium in
      rice (Oryza sativa L.): A combined study using 1, 2-dimensional electrophoresis
      and SR-XRF techniques.
AB  - Mercury (Hg) is a hazardous chemical in the environment and can accumulate in the
      food chain. Selenium (Se) is a necessary element for human health and has
      antagonistic effects on Hg toxicity. In this work, we investigated the effect of
      Se on Hg containing and Hg-responsive proteins in rice using 1, 2-dimensional
      electrophoresis combined with SR-XRF techniques. Two weeks old rice seedlings
      were exposed to Hg and/or Se compounds. After 21days proteins in the rice roots
      were separated by electrophoresis and their metal contents were determined by X
      ray fluorescence to identify Hg and Se responsive biomolecules. The results show
      that under Hg stress alone Hg is bound to proteins with molecular weights of 15
      25kDa. With the addition of Se, a new Hg-containing protein band in the 55-70kDa
      range was also found, while the content of Hg in the 15-25kDa proteins decreased.
      Ten and nine new protein spots were identified after adding Se to inorganic Hg
      and methylmercury exposed roots, respectively. Adding Se regulates the abundance
      of proteins associated with carbohydrate and energy metabolism, stress response,
      cell cycle, and DNA replication indicating that these proteins mediate the
      antagonism of Se against Hg toxicity. This study helps us to better understand
      the molecular mechanism of Hg tolerance as well as the molecular antagonism
      between Hg and Se in rice plants.

PMID- 29066365
TI  - The enzyme-substrate complex as a cat state: A toy quantum analog.
AB  - We introduce a quantum model system incorporating qualitative aspects of
      tunneling in enzyme action and analyze the possibilities of quantum superposition
      of several conformations of the enzyme-substrate complex. There is a potential
      barrier in each conformation which for simplicity's sake is assumed to be of zero
      width making the system explicitly solvable. Such a system exhibits generic
      features of quantum dynamics that should be present to some extent in real enzyme
      action. We find that depending on the parameters of the system, the rate of
      conversion of substrate to product can be either enhanced or suppressed in
      relation to the rates that can be achieved in fixed conformations. There are also
      solutions in which a component of the quantum state exists as a bound state,
      something that cannot happen in a fixed conformation. This may provide some
      measure of stability to the complex. Paradoxically enough, superposition of a
      finite barrier with an infinite barrier can also enhance the conversion of
      substrate to product in relation to the finite barrier alone. We suggest that
      binding to a superposition of conformations could be preferred in relation to
      binding to a fixed conformation, and analyze the conditions in living cells that
      could support enzyme action by conformations in superposition.

PMID- 29066366
TI  - Normal macromolecular clearance out of the ventricles is delayed in
      hydrocephalus.

PMID- 29066367
TI  - Brain metabolic correlates of CSF Tau protein in a large cohort of Alzheimer's
      disease patients: A CSF and FDG PET study.
AB  - AIMS: Physiopathological mechanisms of Alzheimer's disease (AD) are still matter
      of debate. Especially the role of amyloid beta and tau pathology in the
      development of the disease are still matter of debate. Changes in tau and amyloid
      beta peptide concentration in cerebrospinal fluid (CSF) and hypometabolic
      patterns at fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning are considered
      as biomarkers of AD. The present study was aimed to evaluate the relationships
      between the concentrations of CSF total Tau (t-Tau), phosphorilated Tau (p-Tau)
      and Abeta1-42 amyloid peptide with 18F-FDG brain distribution in a group of
      patients with AD. MATERIALS AND METHODS: We examined 131 newly diagnosed AD
      patients according to the NINCDS-ADRDA criteria and 20 healthy controls. The mean
      (+/-SD) age of the patients was 70 (+/-7) years; 57 were male and 74 were female.
      All patients and controls underwent a complete clinical investigation, including
      medical history, neurological examination, mini-mental state examination (MMSE),
      a complete blood screening (including routine exams, thyroid hormones and a
      complete neuropsychological evaluation). Structural MRI was performed not earlier
      than 1 month before the 18F-FDG PET/CT. The following patients were excluded:
      those with isolated deficits and/or unmodified MMSE (=25/30) on revisit (period
      of follow-up: 6, 12 and 18 months); patients who had had a clinically manifest
      acute stroke in the last 6 months with a Hachinsky score greater than 4; and
      patients with radiological evidence of subcortical lesions. All AD patients were
      taken off cholinesterase inhibitor treatment throughout the study. We performed
      lumbar puncture and CSF sampling for diagnostic purposes 2 weeks (+/-2 days)
      before the PET/CT scan. The relationship between brain F-FDG uptake and CSF
      biomarkers was analysed using statistical parametric mapping (SPM8; Wellcome
      Department of Cognitive Neurology, London, UK) implemented in Matlab R2012b using
      the MMSE score, sex and age, and other CSF biomarkers as covariates. RESULTS: t
      Tau, p-Tau and Abeta(1-42) in CSF resulted 774 +/- 345 pg/ml, 98 +/- 64 pg/ml and
      348.8 +/- 111 pg/ml respectively. SPM analysis showed a significant negative
      correlation between CSF t-Tau and 18F FDG uptake in right temporal, parietal and
      frontal lobe (Brodmann areas, BA, 20, 40 and 8; P fdr and few corr < 0.001, ke
      19534). We did not find any significant relationships with other CSF biomarkers.
      CONCLUSIONS: t-Tau deposition in brain is related to temporal, parietal and
      frontal hypometabolism in AD.

PMID- 29066368
TI  - Investigating the efficacy of a combination Abeta-targeted treatment in a mouse
      model of Alzheimer's disease.
AB  - Amyloid-beta peptide (Abeta) plays a critical role in the pathogenesis of
      Alzheimer's disease (AD). Here, we explored the use of a combination treatment to
      reduce amyloid load through microglial phagocytosis in a mouse model of AD. We
      hypothesized that using an initial treatment of magnetic resonance image guided
      focused ultrasound (MRIgFUS) to transiently increase the blood-brain barrier
      (BBB) permeability and enhance the delivery of an Abeta-antibody (BAM-10),
      followed by scyllo-inositol treatment would result in accelerated clearance.
      TgCRND8 mice expressing both Swedish (KM670/671NL) and Indiana (V717F) APP
      mutations under the hamster prion (PrP) promoter at 5 months of age were either
      treated with scyllo-inositol or received an initial MRIgFUS treatment delivering
      BAM-10 prior to scyllo-inositol treatment for one month. Treated animals and
      untreated TgCRND8 littermates were then sacrificed at 6 months of age, and their
      brains were processed for immunohistochemistry and immunofluorescence. Amyloid
      load was quantified and analyzed through immunohistochemical staining. Astrocyte
      and microglial activation were quantified and analyzed through immunofluorescent
      staining. We found that both the scyllo-inositol treatment and combination
      treatment, MRIgFUS/BAM10+scyllo-inositol, significantly reduced amyloid load and
      astrocyte activation in the hippocampus and the cortex. Furthermore, in both
      treatment paradigms microglial activation and phagocytosis was increased in
      comparison to the untreated mice. There were no differences detected between the
      two treatment paradigms. We propose that the 30-day scyllo-inositol treatment
      saturated the early benefit of the MRIgFUS/BAM-10 treatment. In the future,
      multiple FUS treatments combined with BAM-10 throughout the duration of scyllo
      inositol treatment may lead to more effective amyloid clearance.

PMID- 29066369
TI  - Astrocytic glutamatergic transporters are involved in Abeta-induced synaptic
      dysfunction.
AB  - In Alzheimer's disease (AD), dementia severity correlates most strongly with
      decreased synapse density in the hippocampus and cerebral cortex. Although
      studies in rodents have established that hippocampal long-term potentiation (LTP)
      is inhibited by soluble oligomers of beta-amyloid (Abeta), the synaptic
      mechanisms remain unclear. Here, field excitatory postsynaptic potentials (fEPSP)
      recordings were made in the CA1 region of mouse hippocampal slices. The medium of
      APP-expressing CHO cells, which contain soluble forms of Abeta including small
      oligomers, inhibited LTP and facilitated long-term depression (LTD), thus making
      the LTP/LTD curve shift toward the right. This phenomenon could be mimicked by
      the non-selective glutamate transporter inhibitor, DL-TBOA. More specifically,
      the Abeta impaired LTP and facilitated LTD were occluded by the selective
      astrocytic glutamate transporter inhibitors, TFB-TBOA. In cultured astrocytes,
      the Abeta oligomers also decrease astrocytic glutamate transporters (EAAT1,
      EAAT2) expression. We conclude that soluble Abeta oligomers decrease the
      activation of astrocytic glutamate transporters, thereby impairing synaptic
      plasticity.

PMID- 29066371
TI  - Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and
      Portal Vein Thrombosis.
AB  - BACKGROUND & AIMS: Vitamin K antagonists (VKAs) promote recanalization of portal
      vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT
      recanalization might be offset by major and minor bleeding associated with use of
      anticoagulants. We evaluated harmful and beneficial effects of VKA in patients
      with PVT and cirrhosis. METHODS: We performed a retrospective study of 63
      consecutive patients with cirrhosis given anticoagulants for the first detection
      of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding
      events in these patients and compared them with those from patients without
      cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in
      the therapeutic range, based on the international normalized ratio, was used to
      determine the quality of anticoagulation. We also collected data from 139
      patients with cirrhosis who did not receive VKAs (controls), to analyze portal
      hypertension-related events. We performed survival analyses to determine the
      effects of VKA in patients with PVT vs controls. RESULTS: The group with VTE and
      the group with PVT were comparable in age, sex, and time in the therapeutic
      range, but patients with VTE received VKAs for a longer time period (31.1 +/-
      16.9 mo vs 23.3 +/- 16.2 mo; P = .002). The incidence of major or minor bleeding
      was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P =
      .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major
      bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019),
      but there were no significant differences in other types of major bleeding (P =
      .376). Patients with PVT and controls had the same rate of upper-gastrointestinal
      bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was
      independently associated with increased portal hypertension-related event-free
      and transplantation-free survival times. CONCLUSIONS: In a retrospective analysis
      of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to
      increase risk of minor bleeding, compared with patients without cirrhosis given
      VKA. However, this risk is offset by the ability of VKA to increase portal
      hypertension-related, event-free, and transplantation-free survival of patients
      with PVT recanalization. Portal hypertension, rather than anticoagulants, could
      account for the difference in risk of major bleeding between patients with PVT vs
      patients with VTE.

PMID- 29066370
TI  - Factors Associated With Prevalence and Treatment of Primary Biliary Cholangitis
      in United States Health Systems.
AB  - BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC)
      varies widely. Demographic features and treatment patterns are not well
      characterized in the United States (US). We analyzed data from the Fibrotic Liver
      Disease (FOLD) Consortium, drawn from 11 geographically diverse health systems,
      to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We
      developed a validated electronic health record-based classification model to
      identify patients with PBC in the FOLD database from 2003 through 2014. We used
      multivariable modeling to assess the effects of factors associated with PBC
      prevalence and treatment with ursodeoxycholic acid (UDCA). RESULTS: We identified
      4241 PBC cases among over 14.5 million patients in FOLD health systems; median
      follow-up was 5 years. Accuracy of the classification model was excellent, with
      an area under the receiver operating characteristic curve value of 93%, 94%
      sensitivity, and 87% specificity. The average patient age at diagnosis was 60
      years; 21% were Hispanic, 8% were African American, and 7% were Asian
      American/American Indian/Pacific Islander. Half of the cohort (49%) had elevated
      levels of alkaline phosphatase, and overall, 70% were treated with UDCA. The
      estimated 12-year prevalence of PBC was 29.3 per 100,000 persons. Adjusted
      prevalence values were highest among women (42.8 per 100,000), White patients
      (29.6 per 100,000), and patients 60-70 years old (44.7 per 100,000). Prevalence
      was significantly lower among men and African Americans (10.7 and 19.7 per
      100,000, respectively) than women and whites; men and African Americans were also
      less likely to receive UDCA treatment (odds ratios, 0.6 and 0.5, respectively; P
      < .05). CONCLUSIONS: In an analysis of a large cohort of patients with PBC
      receiving routine clinical care, we observed significant differences in PBC
      prevalence and treatment by gender, race, and age.

PMID- 29066372
TI  - Correlates of low physical activity across 46 low- and middle-income countries: A
      cross-sectional analysis of community-based data.
AB  - Physical inactivity accounts for 5.5% of all avoidable global deaths. However, a
      paucity of multinational studies, particularly in low- and middle-income
      countries (LMICs), has investigated correlates of physical activity (PA). Thus,
      we assessed the correlates of PA using cross-sectional, community-based data of
      the World Health Survey including 46 LMICs. PA was assessed by the International
      Physical Activity Questionnaire (IPAQ) and participants were dichotomized into
      those who do (>=150min moderate-vigorous PA per week) and do not (<150min=low PA)
      comply with the World Health Organization (WHO) PA recommendations. Multivariable
      logistic regression was used to assess the PA correlates. The prevalence of low
      PA in 206,356 persons (mean age 38.4years; 49.6% males) was 29.2% (95%CI=28.3%
      30.0%). In the overall sample, female sex, not married/cohabiting, high education
      and wealth, unemployment, and urban setting were significant sociodemographic
      correlates of low PA. In terms of other correlates, inadequate fruit and
      vegetable intake, subsyndromal depression, worse sleep/energy and cognition,
      visual impairment, hearing problems and asthma were associated with not meeting
      the WHO recommendations. There were some variations in the correlates depending
      on age and sex. Interventions should be developed that operate at multiple levels
      of influence and take into account age- and gender-related PA patterns in order
      to assist people in LMICs to comply with the WHO PA recommendations. Researchers,
      funding bodies, practitioners and policymakers in education, mental and physical
      health, and urban planning have a critical role to play.

PMID- 29066373
TI  - Obesity, body image, and its impact on children's eating and exercise behaviors
      in China: A nationwide longitudinal study.
AB  - Body image seems to mediate the association between obesity and health behaviors
      as well as weight control attempts. We examined the distribution of children's
      body image by demographic characteristics and their subsequent associations with
      eating, exercise, and weight change. Child body image and health behaviors from
      the China Health National Survey 2000-2011 were assessed at baseline and in
      follow-up for 6- to 17-year-old children during 2000-2011 using mixed models.
      There was a large discrepancy between children's actual weight status
      (overweight: 16.9%) vs. self-rated body image (fat: 2.4% in 2011). Less than 1%
      of children desired a fat body; girls were more likely to want to be thin (52.5%
      vs. 40.9%) than boys. About 11% of children needed to lose weight in order to be
      at their desired baseline. During follow-up, those needing weight loss to be as
      desired were more likely to attempt dieting to change their weight (OR, 95%
      CI=1.9, 1.1-3.5 in boys; 1.7, 1.1-2.5 in girls) and less likely to feel they had
      enough physical activity (OR, 95% CI=0.5, 0.4-0.7 in boys; 0.6, 0.5-0.9 in
      girls), although their weight gain had been significantly higher than those
      having consistent self and desired body images (beta [SE]=0.4 [0.1] in boys; 0.2
      [0.1] in girls, all p<0.05). However, no significant difference was shown in
      subsequent health behaviors among overweight children by body image discrepancy.
      The discrepancy in self vs. desired body image motivated children to change their
      obesity-related health behaviors among non-overweight children in China.

PMID- 29066374
TI  - Projected impacts of federal tax policy proposals on mortality burden in the
      United States: A microsimulation analysis.
AB  - The public health consequences of federal income tax policies that influence
      income inequality are not well understood. I aimed to project the impacts on
      mortality of modifying federal income tax structures based on proposals by two
      recent United States (U.S.) Presidential candidates: Donald Trump and Senator
      Bernie Sanders. I performed a microsimulation analysis using the latest U.S.
      Internal Revenue Service public-use tax file with state identifiers (2008 tax
      year), containing nationally-representative data from 139,651 tax returns. I
      considered five tax plan scenarios: 1) actual 2008 tax structures; proposals in
      2016 by then-candidates 2) Trump and 3) Sanders; 4) a modified Sanders plan with
      higher top tax rates (75%); and 5) a modified Sanders plan with higher top rates
      plus revenue redistribution to lower-income households (<$40,000/year). I
      combined projected changes in income inequality with vital statistics data and
      past estimates of linkages between income inequality, income, and mortality.
      29,689 (95% CI: 10,865-48,920) more deaths/year and 31,302 (95% CI: 11,455
      51,577) fewer deaths/year from all causes are anticipated under the Trump and
      Sanders plans, respectively. Under the modified Sanders plan including higher top
      rates, 68,919 (95% CI: 25,221-113,561) fewer deaths/year are projected. Under the
      modified Sanders plan with redistribution, 333,504 (95% CI: 192,897-473,787)
      fewer deaths/year are expected. Policies that both raise federal income tax rates
      and redistribute tax revenue could confer large reductions in the total number of
      annual deaths among Americans. In this era of high income inequality and growing
      public support to address the rich-poor gap, policymakers should consider joint
      federal tax and redistributive policies as levers to reduce the burden of
      mortality in the United States.

PMID- 29066375
TI  - Comparing five front-of-pack nutrition labels' influence on consumers'
      perceptions and purchase intentions.
AB  - In 2011, a National Academy of Medicine report recommended that packaged food in
      the U.S. display a uniform front-of-package nutrition label, using a system such
      as a 0-3 star ranking. Few studies have directly compared this to other labels to
      determine which best informs consumers and encourages healthier purchases. In
      2013, we randomized adult participants (N=1247) in an Internet-based survey to
      one of six conditions: no label control; single traffic light; multiple traffic
      light; Facts Up Front; NuVal; or 0-3 star ranking. We compared groups on purchase
      intentions and accuracy of participants' interpretation of food labels. There
      were no differences in the nutritional quality of hypothetical shopping baskets
      across conditions (p=0.845). All labels improved consumers' abilities to judge
      the nutritional quality of foods relative to no label, but the best designs
      varied by outcomes. NuVal and multiple traffic light labels led to the greatest
      accuracy identifying the healthier of two products (p<0.001), while the multiple
      traffic light also led to the most accurate estimates of saturated fat, sugar,
      and sodium (p<0.001). The single traffic light outperformed other labels when
      participants compared nutrient levels between similar products (p<0.03).
      Single/multiple traffic light and Facts Up Front labels led to the most accurate
      calories per serving estimations (p<0.001). Although front-of-package labels
      helped participants more accurately assess products' nutrition information
      relative to no label, no conditions shifted adults' purchase intentions. Results
      did not point to a clearly superior label design, but they suggest that a 3-star
      label might not be best for educating consumers.

PMID- 29066376
TI  - A de novo mutation in RPL10 causes a rare X-linked ribosomopathy characterized by
      syndromic intellectual disability and epilepsy: A new case and review of the
      literature.
AB  - Intellectual disability (ID) affects 1-2% of the general population and up to 50%
      of those with ID are estimated to have an underlying genetic cause. Next
      generation sequencing provides an efficient means to identify the molecular
      causes of monogenic forms of ID. Here we present an 18 year old male with severe
      ID, absent speech, microcephaly, ataxia, dysmorphic facial features, and a
      refractory, early-onset seizure disorder. Exome sequencing revealed a rare de
      novo mutation in the X-linked gene RPL10 (c.232A > G, p.K78E). Previous reports
      of inherited mutations in RPL10 have suggested a role for the gene in
      neurodevelopment and the individual reported shows marked similarities to three
      members of a family with the same mutation reported in the literature. The p.K78E
      substitution appears to be associated with severe microcephaly, seizures, hearing
      loss, growth retardation, cardiac defects, and dysmorphic facial features. This
      is the first instance that a de novo mutation in RPL10 has been reported.

PMID- 29066377
TI  - Mice with type 1 diabetes exhibit increased susceptibility to influenza A virus.
AB  - Type 1 diabetes (T1D) is a metabolic disease induced by abnormal insulin
      secretions from damaged islet B cells. Clinical observations have shown that T1D
      patients are more easily infected by influenza A virus (IAV) and suffer more
      serious symptoms than non-T1D patients. To investigate the susceptibility of T1D
      mice to IAV, a T1D mouse model was built by intraperitoneal injection of diluted
      streptozotocin (STZ) over 5 consecutive days, followed by infection with three
      subtypes of IAV (H1N1/H5N1/H7N2). The T1D-infected mice showed more serious
      clinical symptoms and lower survival rates than the non-T1D infected mice. The
      hematoxylin and eosin (H&E) staining results revealed an increase in serious
      pathological damage to the lung and pancreas in T1D-infected mice.
      Immunohistochemistry results indicated higher IAV loads and a more extensive
      distribution of positive signals in the lungs and pancreas of T1D-infected mice
      than in those of non-T1D infected mice. Furthermore, according to real-time
      quantitative polymerase chain reaction (PCR) results, viral replication appeared
      to occur more easily in the lungs of T1D-infected mice. Thus, T1D-infected mice
      exhibited higher susceptibility to IAV than did normal mice. This study
      contributes a mouse model suitable for T1D research as well as valuable
      information about the mechanism underlying T1D patients' increased susceptibility
      to IAV.

PMID- 29066378
TI  - The influence of tissue antioxidant enzymes and inflammatory cascade in pathology
      of cystitis: An experimental rat model.
AB  - We evaluate the role of antioxidant enzyme status and inflammatory cascade in
      disease progression of cystitis in a rat model. The animals were injected with
      clinically isolated Uropathogenic Escherichia coli (UPEC) and study the effect of
      various antioxidant enzymes and inflammatory markers in disease pathology on the
      0th day, 12 h and 7th day of infection. The antioxidant status of bladder tissue
      was decreased during the 7th day of infection. Lipid peroxidation marker MDA was
      increased on the 7th day of infection in rats. The histopathology of bladder
      tissue shows severe inflammation and edema. This study reveals the role of
      decreased antioxidant status during infection play a vital role in upregulation
      of inflammation and tissue destruction.

PMID- 29066379
TI  - Changes on the activity of cholinesterase's in an immunomodulatory response of
      cattle infected by Listeria monocytogenes.
AB  - The aim of this study was to evaluate whether Listeria monocytogenes infection
      alters the activity of cholinesterases in cattle to module their inflammatory
      response and neurotransmission. Thus, ten male bovines (Holstein) were divided
      into two groups of five animals each: uninfected (control) and L. monocytogenes
      infected. Blood samples were collected on days 0, 7 and 14 post-infection (PI) to
      evaluate the activity of acetylcholinesterase (AChE) in the blood, and seric
      butyrylcholinesterase (BChE) activity, as well as total protein, albumin,
      globulin and C-reactive protein (CPR) levels in serum. The AChE activity and
      acetylcholine (ACh) levels were measured in the central nervous system on day 14
      PI, and histopathological analyses were also performed. The infected animals did
      not show apparent clinical signs of listeriosis, however histopathological
      alterations were seen in the intestines and spleens. On days 7 and 14 PI, AChE
      activity in the blood was lower in infected animals, as well the seric BChE
      activity on day 7 PI. In the cerebral cortex and cerebellum, AChE activity was
      lower in infected animals compared to the control group, while the ACh levels
      were higher in the cerebral cortex compared to uninfected animals. Moreover,
      seric levels of total protein, globulin and CRP were higher in infected animals
      on days 7 and 14 PI compared to the control group. Therefore, we concluded that
      acute infection by L. monocytogenes alters the cholinergic system through the
      reduction of cholinesterase enzymes in the blood, serum and cerebral tissues as
      an adaptive response to an anti-inflammatory effect in order to increase the ACh
      levels, an anti-inflammatory molecule with an important role in the host
      immunomodulation.

PMID- 29066380
TI  - Immune response of a commercial vaccine against Leptospira interrogans:
      Antibodies and cytokine levels.
AB  - Good vaccines should confer protection against specific pathogens in experimental
      and field conditions. However, some commercial vaccines are not capable to confer
      protection to animals, being inefficient in a bovine vaccine program. In this
      sense, the aim of this study was to evaluate the antibody levels involved in the
      immune response in vaccinated cows against leptospirosis, as well as acute phase
      protein and the immunological markers in a vaccine program in beef cattle. Twenty
      non-lactating cows, negative for leptospirosis and without vaccination against
      this disease were evaluated during five months. The herd was divided into two
      groups named as A (the control group) and B (the vaccinated group). Ten cows from
      the group B received an initial dose (5 mL) of vaccine on day 0 and one booster
      dose (5 mL) on day 29. In order to evaluate humoral response (MAT - titration
      1:25), cytokine levels (tumor necrosis factor (TNF) and interleukin-10 (IL-10)),
      and C-reactive protein levels (an acute phase protein), blood samples were
      evaluated on days 0, 29, 40, 83 and 144 after vaccination. In none of the
      evaluated periods it was observed specific antibodies to any of the six serovars
      presents in the vaccine, as well as no difference between groups regarding
      cytokine and C-reactive protein levels. Therefore, the vaccine used did not
      stimulate the immune response of cattle, inferring the absence of protection
      against infections by L. interrogans.

PMID- 29066381
TI  - Silkworm model for Francisella novicida infection.
AB  - Understanding the virulence and pathogenesis of human pathogens using insect
      models is an increasingly popular method. Francisella novicida, which is virulent
      in mice but non-pathogenic to immunocompetent humans, is widely used as an ideal
      candidate for Francisella research. In this study, we developed a silkworm
      (Bombyx mori) infection model for F. novicida by inoculating the hemocoels of
      silkworms with F. novicida. We found that silkworms died within 3-7 days of F.
      novicida infection. However, the deletion mutant of DotU, the core part of type
      VI secretion systems, failed to kill silkworm. In whole silkworm bodies, the
      bacterial load of the DotU deletion mutant was significantly less than that of
      the wild-type strain. Approximately 10-fold increase in bacterial load was
      recorded in hemolymph and subcutaneous tissues compared with that in the silk
      gland, Malpighian tubule, and reproductive organs. The CFU count of the DotU
      deletion mutant in all organs was similar results to the whole body CFU count.
      Confocal microscopy further confirmed the arrested growth of the mutant strain
      within hemocytes. The intracellular growth of F. novicida strains was also
      analyzed using the silkworm ovary-derived cell line BmN4. In BmN4, both CFU count
      assay and confocal microscopy revealed extensive growth of the wild-type strain
      compared with that of the mutant strain. Francisella DotU has already been proven
      as a virulence factor in mammals, and it was also found to be an essential
      virulence factor in our silkworm infection model. Therefore, this silkworm
      infection model is suitable for identifying new virulence factors of Francisella.

PMID- 29066382
TI  - Anti-staphylococcal properties of Eichhornia crassipes, Pistacia vera, and
      Ziziphus amole leaf extracts: Isolates from cattle and rabbits.
AB  - The desideratum aim of the present context was to assess the biopotency of
      methanolic extracts of Eichhornia crassipes (E. crassipes), Pistacia vera (P.
      vera), and Ziziphus amole (Z. amole) leaves against various staphylococcal
      strains, and to quantify the phenolics as well as saponin content in them. The
      antibacterial activity of various concentrations (62.5-1000 MUg/mL) of plant
      extracts was tested against control clinical strains (Staphylococcus aureus ATCC
      25923, S. aureus ATCC 29213, and S. aureus ATCC 43300), methicillin-resistant S.
      aureus (MRSA1 and MRSA2), oxacillin sensitive S. aureus (SOSA1 and SOSA2), and
      coagulase-negative Staphylococcus epidermidis (CoNS1, CoNS2, and CoNS3) using
      disc diffusion assay. Leaf extracts of the three plants exhibited pronounced
      growth inhibitory characteristics against staphylococci in a dose dependent
      manner. E. crassipes extract depicted the highest relative percentage inhibition
      values against control clinical strains (68.6 +/- 0.5%), while P. vera (68.6 +/-
      0.3%) and Z. amole (74.79 +/- 0.3%) extracts showed pronounced relative
      inhibition values against staphylococcal strains isolated from cattle. Total
      phenols and saponin content of leaf extracts were investigated by standard in
      vitro methods. The methanolic extracts of these plants were found to comprise
      substantial content of phenolics and saponin at varying levels. The highest value
      of phenolics was estimated in P. vera extract (60.0 +/- 1.3 mg gallic acid/g
      extract), followed by Z. amole (33.6 +/- 1.4 mg gallic acid/g extract), and E.
      crassipes (23.0 +/- 1.3 mg gallic acid/g extract). Saponin content for P. vera,
      Z. amole, and E. crassipes extracts were estimated as 41.0 +/- 1.3, 35.8 +/- 1.3,
      and 25.0 +/- 1.2 mg diosgenin/g extract, respectively. The outcome of this study
      suggested the exploitation of methanolic extract of P. vera, Z. amole, and E.
      crassipes leaves for their possible application in ethnomedicine, particularly as
      drugs preparation against staphylococcal infections. In conclusion, the study
      indicates the biopotency of these plants against pathogenic MRSA present in
      cattle, and SOSA as well as CoNS bacteria present in rabbits, which could be a
      serious issue for livestock.

PMID- 29066383
TI  - The origins of the British Neuroscience Association.
AB  - I describe the origins of the British Neuroscience Association (BNA) based on new
      documents which I have discovered. The foundation of the Brain Research
      Association (BRA) on February 23rd 1968 was influenced by IBRO, notably its two
      UK Council members, and by many UK neuroscientists, especially the London-based
      Black Horse Group. The BRA changed its name to the BNA in 1996. The documents are
      in the Wellcome Trust Archives.

PMID- 29066384
TI  - Development of a validated HPLC method for the quantitative determination of
      trelagliptin succinate and its related substances in pharmaceutical dosage forms.
AB  - Trelagliptin succinate is a dipeptidyl peptidase IV (DPP-4) inhibitor which is
      used as a new long-acting drug for once-weekly treatment of type 2 diabetes
      mellitus (DM). In the present study, a rapid, sensitive and accurate high
      performance liquid chromatography (HPLC) method was developed and validated for
      separation and determination of trelagliptin succinate and its eight potential
      process-related impurities. The chromatographic separation was achieved on a
      Waters Xselect CSHTM C18 (250mm*4.6mm, 5.0MUm) column. The mobile phases
      comprised of 0.05% trifluoroacetic acid in water as well as acetonitrile
      containing 0.05% trifluoroacetic acid. The compounds of interest were monitored
      at 224nm and 275nm. The stability-indicating capability of this method was
      evaluated by performing stress test studies. Trelagliptin succinate was found to
      degrade significantly in acid, base, oxidative and thermal stress conditions and
      only stable in photolytic degradation condition. The degradation products were
      well resolved from the main peak and its impurities. In addition, the major
      degradation impurities formed under acid, base, oxidative and thermal stress
      conditions were characterized by ultra-high-performance liquid chromatography
      coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ
      Orbitrap). The method was validated to fulfill International Conference on
      Harmonisation (ICH) requirements and this validation included specificity,
      linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy,
      precision and robustness. The developed method in this study could be applied for
      routine quality control analysis of trelagliptin succinate tablets, since there
      is no official monograph.

PMID- 29066385
TI  - Nebulized coenzyme Q10 nanosuspensions: A versatile approach for pulmonary
      antioxidant therapy.
AB  - Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary
      supplement which has been proposed as adjuvant in the treatment of cardiovascular
      disorders and cancer for its protective and immunostimulating activities. The aim
      of this work was the production by high-pressure homogenization, characterization
      and stability investigation of three different CoQ10 nanosuspensions designed to
      be administered to the lungs by nebulization. Three surfactants, i.e. lecithin,
      PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations.
      Preparations were identified as nanosuspensions (particle size in the range 35
      60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a
      core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was
      in all the cases around 30% of the loaded dose. The nanosuspension containing
      PEG32 stearate presented the highest respirable fraction (70.6%) and smallest
      MMAD (3.02MUm). Stability tests showed that the most stable formulation, after
      90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin
      formulation. Interestingly, those formulations were demonstrated to be suitable
      also for nebulizers using other mechanisms of aerosol production such as
      ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular
      toxicity of the formulations and their single components using A549 human lung
      cells showed no obvious cytotoxicity for the formulations containing lecithin and
      PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma
      membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present
      in the formulation with CoQ10.

PMID- 29066386
TI  - Use of cable guide while performing segmental mandibulectomy using Gigli saw.
AB  - Segmental mandibulectomies are performed commonly in patients having benign or
      malignant pathologies of mandible. For this purpose, Gigli saw is used frequently
      by most of the maxillofacial surgeons. The two main challenging tasks while using
      Gigli saw includes passage of the device around the bone which is to be cut and
      the preservation of the underlying soft tissue from getting damaged by the saw
      during its movement. Hence, we propose the use of a "Cable guide with hook" which
      not only helps in easy passage of Gigli saw around the mandible but also prevents
      injury to the underlying soft tissue while performing mandibulectomy.

PMID- 29066388
TI  - Maternal Sleep-Disordered Breathing.
AB  - Emerging literature suggests that sleep-disordered breathing (SDB) worsens over
      the course of pregnancy and is associated with adverse maternal and fetal
      outcomes. Earlier studies, using mainly snoring as a surrogate marker for SDB,
      have shown an increase in the prevalence of SDB during pregnancy compared with
      that in the pregravid state. More recently, prospective observational studies in
      which the investigators ascertained SDB by using complete polysomnography have
      shown a prevalence ranging from approximately 17% to 45% in the third trimester.
      Pregnancy itself can be associated with daytime hypersomnolence, so complaints of
      increasing fatigue and sleepiness during pregnancy are not specific for SDB.
      Moreover, snoring in isolation also has relatively poor sensitivity and
      specificity as a screening tool for diagnosing maternal SDB. The indications for
      screening for SDB during routine obstetric prenatal visits are still unclear, but
      observational studies indicate that maternal SDB is linked with the development
      of adverse pregnancy outcomes, such as gestational hypertension and gestational
      diabetes mellitus. Some studies also have identified a relationship between
      maternal SDB and the delivery of infants who are small for gestational age. Aside
      from a few small interventional studies of CPAP in pregnant patients with
      gestational hypertension, little currently is known about whether treatment of
      SDB during pregnancy improves clinical outcomes for the mother and/or baby.
      Additional current knowledge gaps include elucidating underlying mechanisms of
      maternal SDB, determining optimal treatment strategies, and understanding the
      trajectory of SDB after delivery.

PMID- 29066387
TI  - Clinical Course of Sarcoidosis in World Trade Center-Exposed Firefighters.
AB  - BACKGROUND: Sarcoidosis is believed to represent a genetically primed, abnormal
      immune response to an antigen exposure or inflammatory trigger, with both genetic
      and environmental factors playing a role in disease onset and phenotypic
      expression. In a population of firefighters with post-World Trade Center (WTC)
      9/11/2001 (9/11) sarcoidosis, we have a unique opportunity to describe the
      clinical course of incident sarcoidosis during the 15 years postexposure and, on
      average, 8 years following diagnosis. METHODS: Among the WTC-exposed cohort, 74
      firefighters with post-9/11 sarcoidosis were identified through medical records
      review. A total of 59 were enrolled in follow-up studies. For each participant,
      the World Association of Sarcoidosis and Other Granulomatous Diseases organ
      assessment tool was used to categorize the sarcoidosis involvement of each organ
      system at time of diagnosis and at follow-up. RESULTS: The incidence of
      sarcoidosis post-9/11 was 25 per 100,000. Radiographic resolution of
      intrathoracic involvement occurred in 24 (45%) subjects. Lung function for nearly
      all subjects was within normal limits. Extrathoracic involvement increased, most
      prominently joints (15%) and cardiac (16%) involvement. There was no evidence of
      calcium dysmetabolism. Few subjects had ocular (5%) or skin (2%) involvement, and
      none had beryllium sensitization. Most (76%) subjects did not receive any
      treatment. CONCLUSIONS: Extrathoracic disease was more prevalent in WTC-related
      sarcoidosis than reported for patients with sarcoidosis without WTC exposure or
      for other exposure-related granulomatous diseases (beryllium disease and
      hypersensitivity pneumonitis). Cardiac involvement would have been missed if
      evaluation stopped after ECG, 48-h recordings, and echocardiogram. Our results
      also support the need for advanced cardiac screening in asymptomatic patients
      with strenuous, stressful, public safety occupations, given the potential
      fatality of a missed diagnosis.

PMID- 29066389
TI  - Disease Severity Dependence of the Longitudinal Association Between CT Lung
      Density and Lung Function in Smokers.
AB  - BACKGROUND: In smokers, the lung parenchyma is characterized by inflammation and
      emphysema, processes that can result in local gain and loss of lung tissue. CT
      measures of lung density might reflect lung tissue changes; however, longitudinal
      data regarding the effects of CT lung tissue on FEV1 in smokers with and without
      COPD are scarce. METHODS: The 15th percentile of CT lung density was obtained
      from the scans of 3,390 smokers who completed baseline and 5-year follow-up of
      the Genetic Epidemiology of COPD (COPDGene) study visits. The longitudinal
      relationship between total lung capacity-adjusted lung density (TLC-PD15) and
      FEV1 was assessed by using multivariable mixed models. Separate models were
      performed in smokers at risk, smokers with preserved ratio and impaired
      spirometry (PRISm), and smokers with COPD according to the Global Initiative for
      Chronic Obstructive Lung Disease (GOLD) staging system. RESULTS: The direction of
      the relationship between lung density and lung function was GOLD stage dependent.
      In smokers with PRISm, a 1-g/L decrease in TLC-PD15 was associated with an
      increase of 2.8 mL FEV1 (P = .02). In contrast, among smokers with GOLD III to IV
      COPD, a 1-g/L decrease in TLC-PD15 was associated with a decrease of 4.1 mL FEV1
      (P = .002). CONCLUSIONS: A decline in TLC-PD15 was associated with an increase or
      decrease in FEV1 depending on disease severity. The associations are GOLD stage
      specific, and their presence might influence the interpretation of future studies
      that use CT lung density as an intermediate study end point for a decline in lung
      function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL:
      www.clinicaltrials.gov.

PMID- 29066390
TI  - Pulmonary Nodules: A Small Problem for Many, Severe Distress for Some, and How to
      Communicate About It.
AB  - Every year, millions of patients are diagnosed with pulmonary nodules, and as
      increasing numbers of people undergo lung cancer screening, even more patients
      will be found to have a nodule. The vast majority of patients cannot benefit from
      the detection of a pulmonary nodule because most are benign. Accordingly, it is
      important to develop strategies to minimize harm, in particular the distress of a
      "near-cancer" diagnosis. In other settings, communication strategies are critical
      mediators of patient-centered outcomes for those with cancer and those at-risk of
      cancer. We conducted multiple studies to characterize the experience of patients
      with the diagnosis and evaluation of incidental pulmonary nodules, measure
      patient-centered outcomes for patients with pulmonary nodules, and determine the
      association of patient-clinician communication practices with those outcomes. We
      learned that a substantial proportion of patients experience distress and
      inadequate communication about pulmonary nodules and their evaluation, and yet
      many clinicians are unaware of the degree to which some patients are affected by
      the finding of a pulmonary nodule. The present review provides a comprehensive
      summary of our results and offers suggestions for how clinicians can best provide
      high-quality communication for their patients.

PMID- 29066391
TI  - Gastrojejunostomy versus duodenal stent placement for gastric outlet obstruction
      in patients with unresectable pancreatic cancer.
AB  - BACKGROUND/OBJECTIVE: Whether gastrojejunostomy (GJJ) or duodenal stent (DS)
      placement is preferable for treatment of gastric outlet obstruction (GOO) in
      patients with unresectable pancreatic cancer is unclear. We compared the
      usefulness of GJJ with that of DS placement in these patients. METHODS: We
      retrospectively reviewed 66 consecutive patients with unresectable pancreatic
      cancer who underwent GJJ or DS placement for symptomatic GOO. RESULTS: We
      analyzed 30 patients who underwent GJJ and 23 who underwent DS placement.
      Peritoneal metastasis was more common in the DS group. Median survival after the
      first intervention was similar in both groups. Although clinical success
      (maintaining a GOO Scoring System score >=2 for more than 7 days) rate was
      significantly higher in the GJJ group (100% vs. 81%), clinical benefit
      (maintaining a score >=2 for more than half of their survival after the first
      intervention) rate was similar between the GJJ and DS groups (66.7% vs. 69.7%),
      even among patients who survived for >=90 days (73.3% vs. 75.0%). Further, the
      proportion of patients who could receive planned chemotherapy after the first
      intervention was higher and the time to administration of chemotherapy was
      significantly shorter in the DS group (9 vs. 32 days). Major complication rate
      was similar in both groups. CONCLUSIONS: These findings suggest that DS placement
      is as effective as GJJ for the treatment of GOO in patients with unresectable
      pancreatic cancer, even in those with a long life expectancy. DS placement might
      be more beneficial than GJJ in patients for whom chemotherapy is planned.

PMID- 29066392
TI  - Structured near-infrared Magnetic Circular Dichroism spectra of the Mn4CaO5
      cluster of PSII in T. vulcanus are dominated by Mn(IV) d-d 'spin-flip'
      transitions.
AB  - Photosystem II passes through four metastable S-states in catalysing light-driven
      water oxidation. Variable temperature variable field (VTVH) Magnetic Circular
      Dichroism (MCD) spectra in PSII of Thermosynochococcus (T.) vulcanus for each S
      state are reported. These spectra, along with assignments, provide a new window
      into the electronic and magnetic structure of Mn4CaO5. VTVH MCD spectra taken in
      the S2 state provide a clear g=2, S=1/2 paramagnetic characteristic, which is
      entirely consistent with that known by EPR. The three features, seen as positive
      (+) at 749nm, negative (-) at 773nm and (+) at 808nm are assigned as 4A->2E spin
      flips within the d3 configuration of the Mn(IV) centres present. This assignment
      is supported by comparison(s) to spin-flips seen in a range of Mn(IV) materials.
      S3 exhibits a more intense (-) MCD peak at 764nm and has a stronger MCD
      saturation characteristic. This S3 MCD saturation behaviour can be accurately
      modelled using parameters taken directly from analyses of EPR spectra. We see no
      evidence for Mn(III) d-d absorption in the near-IR of any S-state. We suggest
      that Mn(IV)-based absorption may be responsible for the well-known near-IR
      induced changes induced in S2 EPR spectra of T. vulcanus and not Mn(III)-based,
      as has been commonly assumed. Through an analysis of the nephelauxetic effect,
      the excitation energy of S-state dependent spin-flips seen may help identify
      coordination characteristics and changes at each Mn(IV). A prospectus as to what
      more detailed S-state dependent MCD studies promise to achieve is outlined.

PMID- 29066393
TI  - Mutations in algal and cyanobacterial Photosystem I that independently affect the
      yield of initial charge separation in the two electron transfer cofactor
      branches.
AB  - In Photosystem I, light-induced electron transfer can occur in either of two
      symmetry-related branches of cofactors, each of which is composed of a pair of
      chlorophylls (ec2A/ec3A or ec2B/ec3B) and a phylloquinone (PhQA or PhQB). The
      axial ligand to the central Mg2+ of the ec2A and ec2B chlorophylls is a water
      molecule that is also H-bonded to a nearby Asn residue. Here, we investigate the
      importance of this interaction for charge separation by converting each of the
      Asn residues to a Leu in the green alga, Chlamydomonas reinhardtii, and the
      cyanobacterium, Synechocystis sp. PCC6803, and studying the energy and electron
      transfer using time-resolved optical and EPR spectroscopy. Nanosecond transient
      absorbance measurements of the PhQ to FX electron transfer show that in both
      species, the PsaA-N604L mutation (near ec2B) results in a ~50% reduction in the
      amount of electron transfer in the B-branch, while the PsaB-N591L mutation (near
      ec2A) results in a ~70% reduction in the amount of electron transfer in the A
      branch. A diminished quantum yield of P700+PhQ- is also observed in ultrafast
      optical experiments, but the lower yield does not appear to be a consequence of
      charge recombination in the nanosecond or microsecond timescales. The most
      significant finding is that the yield of electron transfer in the unaffected
      branch did not increase to compensate for the lower yield in the affected branch.
      Hence, each branch of the reaction center appears to operate independently of the
      other in carrying out light-induced charge separation.

PMID- 29066394
TI  - Beyond the word and image: II- Structural and functional connectivity of a common
      semantic system.
AB  - Understanding events requires interplaying cognitive processes arising in neural
      networks whose organisation and connectivity remain subjects of controversy in
      humans. In the present study, by combining diffusion tensor imaging and
      functional interaction analysis, we aim to provide new insights on the
      organisation of the structural and functional pathways connecting the multiple
      nodes of the identified semantic system -shared by vision and language (Jouen et
      al., 2015). We investigated a group of 19 healthy human subjects during
      experimental tasks of reading sentences or seeing pictures. The structural
      connectivity was realised by deterministic tractography using an algorithm to
      extract white matter fibers terminating in the selected regions of interest
      (ROIs) and the functional connectivity by independent component analysis to
      measure correlated activities among these ROIs. The major connections link
      ventral neural stuctures including the parietal and temporal cortices through
      inferior and middle longitudinal fasciculi, the retrosplenial and parahippocampal
      cortices through the cingulate bundle, and the temporal and prefrontal structures
      through the uncinate fasciculus. The imageability score provided when the subject
      was reading a sentence was significantly correlated with the factor of anisotropy
      of the left parieto-temporal connections of the middle longitudinal fasciculus. A
      large part of this ventrally localised structural connectivity corresponds to
      functional interactions between the main parietal, temporal and frontal nodes.
      More precisely, the strong coactivation both in the anterior temporal pole and in
      the region of the temporo-parietal cortex suggests dual and cooperating roles for
      these areas within the semantic system. These findings are discussed in terms of
      two semantics-related sub-systems responsible for conceptual representation.

PMID- 29066396
TI  - Serial correlations in single-subject fMRI with sub-second TR.
AB  - When performing statistical analysis of single-subject fMRI data, serial
      correlations need to be taken into account to allow for valid inference.
      Otherwise, the variability in the parameter estimates might be under-estimated
      resulting in increased false-positive rates. Serial correlations in fMRI data are
      commonly characterized in terms of a first-order autoregressive (AR) process and
      then removed via pre-whitening. The required noise model for the pre-whitening
      depends on a number of parameters, particularly the repetition time (TR). Here we
      investigate how the sub-second temporal resolution provided by simultaneous
      multislice (SMS) imaging changes the noise structure in fMRI time series. We fit
      a higher-order AR model and then estimate the optimal AR model order for a
      sequence with a TR of less than 600 ms providing whole brain coverage. We show
      that physiological noise modelling successfully reduces the required AR model
      order, but remaining serial correlations necessitate an advanced noise model. We
      conclude that commonly used noise models, such as the AR(1) model, are inadequate
      for modelling serial correlations in fMRI using sub-second TRs. Rather,
      physiological noise modelling in combination with advanced pre-whitening schemes
      enable valid inference in single-subject analysis using fast fMRI sequences.

PMID- 29066395
TI  - Associations between prenatal, childhood, and adolescent stress and variations in
      white-matter properties in young men.
AB  - OBJECTIVE: Previous studies have shown that both pre- and post-natal adversities,
      the latter including exposures to stress during childhood and adolescence,
      explain variation in structural properties of white matter (WM) in the brain.
      While previous studies have examined effects of independent stress exposures
      within one developmental period, such as childhood, we examine effects of stress
      across development using data from a prospective longitudinal study. More
      specifically, we ask how stressful events during prenatal development, childhood,
      and adolescence relate to variation in WM properties in early adulthood in young
      men recruited from a birth cohort. METHOD: Using data from 393 mother-son pairs
      from a community-based birth cohort from England (Avon Longitudinal Study of
      Parents and Children), we examined how stressful life events relate to variation
      in different structural properties of WM in the corpus callosum and across the
      whole brain in early adulthood in men aged 18-21 years. We distinguish between
      stress occurring during three developmental periods: a) prenatal maternal stress,
      b) postnatal stress within the first four years of life, c) stress during
      adolescence (age 12-16 years). To obtain a comprehensive quantification of
      variation in WM, we assess structural properties of WM using four different
      measures, namely fractional anisotropy (FA), mean diffusivity (MD), magnetization
      transfer ratio (MTR) and myelin water fraction (MWF). RESULTS: The developmental
      model shows that prenatal stress is associated with lower MTR and MWF in the genu
      and/or splenium of the corpus callosum, and with lower MTR in global (lobar) WM.
      Stress during early childhood is associated with higher MTR in the splenium, and
      stress during adolescence is associated with higher MTR in the genu and lower MD
      in the splenium. We see no associations between postnatal stress and variation in
      global (lobar) WM. CONCLUSIONS: The current study found evidence for independent
      effects of stress on WM properties during distinct neurodevelopmental periods. We
      speculate that these independent effects are due to differences in the
      developmental processes unfolding at different developmental time points. We
      suggest that associations between prenatal stress and WM properties may relate to
      abnormalities in neurogenesis, affecting the number and density of axons, while
      postnatal stress may interfere with processes related to myelination or radial
      growth of axons. Potential consequences of prenatal glucocorticoid exposure
      should be considered in obstetric care.

PMID- 29066397
TI  - Molecular cloning and analysis of PGRP-L1 and IMD from silkworm Bombyx mori.
AB  - Peptidoglycan is one of the major components of bacterial cell wall. The innate
      immune system of insects utilizes a group of peptidoglycan recognition proteins
      (PGRPs) for the recognition of specific peptidoglycans and activating immune
      signaling pathways. In Drosophila melanogaster, PGRP-LC and IMD (immune
      deficiency) are two important signaling molecules of the IMD pathway. Here we
      cloned and characterized PGRP-L1 and IMD from the domesticated silkworm Bombyx
      mori (BmPGRP-L1 and BmIMD). BmPGRP-L1 gene consists of five exons that encodes a
      polypeptide of 304 amino acids with a transmembrane region and an extracellular
      PGRP domain. The PGRP domain lacks key residues for the amidase activity. BmIMD
      cDNA encodes a polypeptide of 250 amino acids with a death domain. BmPGRP-L1 and
      BmIMD were expressed in various tissues and induced by bacterial challenges. In
      addition, in vivo blocking of the PGRP domain by the antiserum or purified
      antibody significantly reduced the expression of some antimicrobial peptide
      genes. The extracellular region of BmPGRP-L1 bound to diaminopimelic acid-type
      and lysine-type peptidoglycans. Overexpression of full-length BmIMD in Drosophila
      Schneider 2 cells significantly induced three antimicrobial peptide genes. These
      results suggest that BmPGRP-L1 and BmIMD may be players in the IMD pathway of B.
      mori. This study provides a foundation for further studies on the functions of
      silkworm IMD pathway.

PMID- 29066398
TI  - Characterization of a teleost membrane-associated protein that is involved in the
      regulation of complement activation and bacterial infection.
AB  - In mammals, membrane-associated complement regulatory proteins (MCRP) can protect
      host cells from the damaging of the activated complement. In teleost, few studies
      on the function of MCRP have been documented. In the present report, we
      identified a MCRP (named CsMCRP) from the teleost fish tongue sole Cynoglossus
      semilaevis and examined its immune function. CsMCRP shares moderate sequence
      identities with fish DAF-like molecules. CsMCRP was predicted to be a
      transmembrane protein with three short consensus repeats located in the
      extracellular region. CsMCRP expression occurred in nine different tissues,
      especially blood, and in peripheral blood leukocytes (PBL). Recombinant CsMCRP
      inhibited complement activation and interacted with bacterial pathogen, the
      latter in a highly selective manner. Antibody blocking the CsMCRP on PBL
      significantly inhibited bacterial infection of PBL. These results indicate that
      teleost CsMCRP is both a regulator of complement activation and a cellular
      receptor involved in bacterial invasion.

PMID- 29066399
TI  - Molecular characterization and expression analyses of the Viperin gene in
      Larimichthys crocea (Family: Sciaenidae).
AB  - In this study, we sequenced and characterized an interferon-stimulated gene
      Viperin homologue, LcViperin, from large yellow croaker (Larimichthys crocea).
      The LcViperin encodes 354 amino acids and contains an N-terminal amphipathic
      alpha-helix domain, a radical S-adenosyl-l-methionine (SAM) domain and a highly
      conserved C-terminal domain. The analyses of LcViperin promoter region revealed
      nine kinds of putative transcriptional factor binding sites, including five
      putative ICSBP (IRF-8) binding sites and one putative IRF-1 binding site,
      indicating that the expression of LcViperin might be induced by the type I IFN
      response. Phylogenetic analyses based on amino acid sequences showed that the
      Viperin of large yellow croaker is clustered together with its counterparts from
      other teleost fishes. The Real-time PCR analyses showed that the LcViperin was
      found to be ubiquitously expressed in ten examined tissues in large yellow
      croaker, with predominant expression in peripheral blood, followed by heart and
      gill. Expression analyses showed that the LcViperin was rapidly and significantly
      upregulated in vivo after poly (I:C) challenge in peripheral blood, head kidney,
      spleen and liver tissues. The results indicate that the LcViperin might play a
      pivotal role in antiviral immune responses.

PMID- 29066400
TI  - Colistin antimicrobial susceptibility testing-can the slow and challenging be
      replaced by the rapid and convenient?

PMID- 29066401
TI  - Predominance of G9P[8] rotavirus strains throughout France, 2014-2017.
AB  - OBJECTIVES: Group A rotavirus is a major cause of acute gastroenteritis in young
      children worldwide. A prospective surveillance network has been set up in France
      to investigate rotavirus infections and to detect the emergence of potentially
      epidemic strains. METHODS: From 2014 to 2017, rotavirus-positive stool samples
      were collected from 2394 children under 5 years old attending the paediatric
      emergency units of 13 large hospitals. Rotaviruses were genotyped by RT-PCR with
      regard to their outer capsid proteins VP4 and VP7. RESULTS: Genotyping of 2421
      rotaviruses showed that after a marked increase in G9P[8] (32.1%) during the 2014
      2015 season, G9P[8] became the predominant genotype during the 2015-2016 and 2016
      2017 seasons with detection rates of 64.1% and 77.3%, respectively, whereas
      G1P[8] were detected at low rates of 16.8% and 6.6%, respectively. Phylogenetic
      analysis of the partial rotavirus VP7 and VP4 coding genes revealed that all of
      these G9P [8] strains belonged to the lineage III and the P [8]-3 lineage,
      respectively, and shared the same genetic background (G9-P[8]-I1-R1-C1-M1-A1-N1
      T1-E1-H1) as did most of previously detected G9P[8] strains and particularly the
      emerging G9P[8] strains from the 2004-2005 season in France. CONCLUSIONS: G9P[8]
      rotaviruses have become the predominant circulating genotype for the first time
      since their emergence a decade ago. In the absence of rotavirus immunization
      programmes in France, our data give an insight into the natural fluctuation of
      rotavirus genotypes in a non-vaccinated population and provide a base line for a
      better interpretation of data in European countries with routine rotavirus
      vaccination.

PMID- 29066402
TI  - How do bacteriophages promote antibiotic resistance in the environment?

PMID- 29066403
TI  - The ClosER study: results from a three-year pan-European longitudinal
      surveillance of antibiotic resistance among prevalent Clostridium difficile
      ribotypes, 2011-2014.
AB  - OBJECTIVES: Until the introduction of fidaxomicin, antimicrobial treatment for
      Clostridium difficile infection (CDI) was limited to metronidazole and
      vancomycin. The changing epidemiology of CDI and the emergence of epidemic C.
      difficile PCR ribotype 027 necessitate continued surveillance to identify shifts
      in antibiotic susceptibility. ClosER, currently the largest pan-European
      epidemiological study of C. difficile ribotype distribution and antibiotic
      susceptibility, aimed to undertake antimicrobial resistance surveillance pre- and
      post-introduction of fidaxomicin. METHODS: Between July 2011 and July 2014, 39
      sites across 22 European countries submitted 2830 C. difficile isolates for
      ribotyping, toxin testing and susceptibility testing to metronidazole,
      vancomycin, fidaxomicin, rifampicin, moxifloxacin, clindamycin, imipenem,
      chloramphenicol and tigecycline. RESULTS: Ribotypes 027, 014, 001, 078, 020, 002,
      126, 015 and 005 were most frequently isolated, and emergent ribotypes 198 and
      356 were identified in Hungary and Italy, respectively. All isolates were
      susceptible to fidaxomicin, with scarce resistance to metronidazole (0.2%,
      6/2694), vancomycin (0.1%, 2/2694) and tigecycline (0%). Rifampicin, moxifloxacin
      and clindamycin resistance was evident in multiple ribotypes. Lack of ribotype
      diversity correlated with greater antimicrobial resistance. Epidemic ribotypes
      (027/001) were associated with multiple antimicrobial resistance, and ribotypes
      017, 018 and 356 with high-level resistance. Additional factors may also
      influence local ribotype prevalence. CONCLUSIONS: Fidaxomicin susceptibility was
      retained post-introduction, and resistance to metronidazole and vancomycin was
      rare. Continued surveillance is needed, with more accurate classification and
      clarification of ribotype subtypes to further understand their role in the spread
      of resistance. Other factors may also influence changes in prevalence of C.
      difficile ribotypes with reduced antibiotic susceptibility.

PMID- 29066404
TI  - One-sixth of inpatients in a Danish infectious disease ward have imported
      diseases: A cross-sectional analysis.
AB  - BACKGROUND: The aim of the study was to describe travel demographics and disease
      patterns of patients hospitalized with travel-related diseases, and assess risk
      factors to improve pre-travel information and post-travel diagnostics and
      treatment. METHODS: The study included all patients hospitalized with travel
      related diseases in 2015 at a Danish infectious diseases ward. Patient data was
      extracted from the in-patient hospital registry. was analyzed regarding
      diagnoses, destination, purpose of travel and pre-travel information. RESULTS:
      240 patients were hospitalized with a total of 289 travel-related diseases,
      accounting for 16.6% (240/1450) of all admissions. Febrile illnesses were the
      most common (39.5%, 114/289) followed by respiratory (19.7%, 57/289) and
      gastrointestinal diagnoses (19.0%, 55/289). Most of the diseases were acquired in
      Sub-Saharan Africa (35.6%, 103/289) followed by South East Asia (27.0%, 78/289),
      and 60.0% (144/240) of the patients were tourists. One-third (36.3%, 81/223) of
      the non-migrants had received pre-travel information. The lowest rate was seen in
      people visiting friends and relatives (18.2%, 6/32). CONCLUSION: Travel-related
      diseases are common among patients admitted to this Danish infectious disease
      ward. Malaria is the most common disease among both travelers and immigrants. In
      approximately one third of all the patients in our study etiology was unknown.

PMID- 29066405
TI  - Effects of Danhong Injection on platelet aggregation in hyperlipidemia rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Danhong Injection (DHI), a Chinese medical
      product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia
      miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus
      tinctorius L., Compositae, Honghua in Chinese), has been reported to have effects
      on inflammatory, anti-fibrinolytic properties, antithrombotic and decrease blood
      lipid. It is extensively used for the clinical treatment of cardiovascular
      disease. This study aimed to investigate the effects of DHI on blood-lipid levels
      and platelet aggregation rate in hyperlipidemia rats. MATERIALS AND METHODS: Rats
      were randomly divided into 6 groups: normal control (NC), model control (MC), DHI
      treated control at doses of 1.0mL/kg, 2.0mL/kg, 4.0mL/kg, respectively, and
      Simvastatin positive control at dose of 2.0mg/kg. All DHI treated groups were
      intraperitoneally injected for 7 days. The effects of DHI on serum triglyceride
      (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and
      high density lipoprotein cholesterol (HDL-C) were evaluated. And platelet
      activating factor (PAF), platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa)
      and 6-keto-prostaglandin F1a (6-K-PGF1a) were determined by enzyme-linked
      immunosorbent assay (ELISA). Moreover, the expression of prostaglandin I-2
      (PGI2), prostaglandin E-2 (PGE2) and thromboxane A2 (TXA2) in liver was
      determined by real-time PCR. RESULTS: Compared with the MC group, the rats
      treated with DHI had significantly reduced TC, TG, LDL-C, FIB, GP IIb/IIIa and
      platelet aggregation. Meanwhile, the thrombin time (TT), activated partial
      thrombin time (APTT), prothrombin time (PT), 6-K-PGF1a was significantly
      increased. Expression of PGI2 and PGE2 mRNA was significantly increased, whereas
      the TXA2 was significantly reduced. CONCLUSIONS: This study demonstrated that the
      blood lipid and platelet aggregation has a regulatory effect after DHI treatment.
      The insights gained from this study will improve understanding of the mechanisms
      involved in the effect of DHI on hyperlipidemia and the pharmacological rationale
      for the use of DHI in diseases caused by formation of thrombosis and lipid
      metabolic disorders.

PMID- 29066406
TI  - An ethnopharmacological survey of medicinal plants traditionally used for cancer
      treatment in the Ashanti region, Ghana.
AB  - AIMS: Cancer represents a major health burden and drain on healthcare resources
      in the world. The majority of the people of Africa still patronize traditional
      medicine for their health needs, including various forms of cancer. The aim of
      the following study is the identification of medicinal plants used for cancer
      treatment by the traditional healers in the Ashanti area of Ghana and to cross
      reference the identified plant species with published scientific literature.
      METHODOLOGY: Validated questionnaires were administered to 85 traditional healers
      in 10 communities within Ashanti region. For cross-validation, also 7 healers
      located outside Ashanti region were investigated to evaluate regional
      differences. Interviews and structured conversations were used to administer the
      questionnaires. Selected herbal material dominantly used by the healers was
      collected and identified. RESULTS: The ethnopharmacological survey revealed 151
      plant species used for cancer treatment. Identified species were classified into
      different groups according to their frequency of use, resulting in the "top-22"
      plants. Interestingly group I (very frequent use) contained 5 plant species
      (Khaya senegalensis, Triplochiton scleroxylon, Azadirachta indica,
      Entandrophragma angolense, Terminalia superba), three of which belong to the
      plant family Meliaceae, phytochemically mainly characterized by the presence of
      limonoids. Cross-referencing of all plants identified by current scientific
      literature revealed species which have not been documented for cancer therapy
      until now. Special interest was laid on use of plants for cancer treatment of
      children. CONCLUSION: A variety of traditionally used anti-cancer plants from
      Ghana have been identified and the widespread use within ethnotraditional
      medicine is obvious. Further in vitro and clinical studies will be performed in
      the near future to rationalize the phytochemical and functional scientific
      background of the respective extracts for cancer treatment.

PMID- 29066407
TI  - The aryloxyalkanoate dioxygenase-12 (AAD-12) protein is not acutely toxic in
      mice.
AB  - Typically, when a protein is orally toxic, it acts via acute mechanisms,
      especially at high doses. Therefore, an acute oral toxicity study is considered
      appropriate for evaluating the safety of transgenic proteins. Soybean plants
      (events DAS-68416-4 and DAS-444O6-6) have been genetically modified to express
      the aryloxyalkanoate dioxygenase-12 (AAD-12) protein. The AAD-12 protein provides
      tolerance to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). This paper
      summarizes the study designs of two acute oral toxicity studies evaluating the
      AAD-12 protein and reports the results of these studies. No mortalities or
      adverse effects were observed in mice when AAD-12 was tested up to a limit dose
      of 5000 mg/kg body weight. Based on the results of these studies, it can be
      concluded that AAD-12 protein, as expressed in genetically modified DAS-68416-4
      and DAS-444O6-6 soybeans, lacks acute toxicity via the oral route.

PMID- 29066408
TI  - Short-term in vitro effects of bisphenol A activity on phenotype and function of
      peripheral blood immune system cells.
AB  - Bisphenol A (BPA) is a phenolic compound being constituent of numerous everyday
      used products. Additionally, good absorption through skin and gastrointestinal
      tract is an unquestionable evidence for high risk of BPA exposure and its
      possible influence on health. Effects of BPA action on cells and tissues are
      associated with its structural and functional similarities to steroid hormones.
      Here we investigated whether BPA could possibly influence immune cells through
      steroid receptors present on majority of these cells. In in vitro experiments
      with 200 nM and 1000 nM BPA concentrations we found that high levels affect
      activation of lymphocytes through increased CD25 expression, with no changes in
      functional response based on IFN-gamma production. We demonstrated that BPA
      influence not only phenotype of monocytes with increased frequency of CD14++CD16-
      subtypes, but also activation inhibition with decline of HLADR expression within
      monocytes. Similarly to lymphocytes, no changes were observed in context of
      monocytes function in BPA-exposed cells. Our study revealed that BPA actions are
      also associated with its direct role in modulation of immune system cells. We
      presume that further experiments would allow establishing connection between
      presented data and increased risk of cancer and metabolic diseases in subject
      exposed to bisphenol A.

PMID- 29066409
TI  - Quality challenges associated with microbial-based cleaning products from the
      Industry Perspective.
AB  - Microbial-based cleaning products (MBCPs) continue to gain popularity in the
      market as environmentally friendly cleaners. The majority of these products
      contain spores of various Bacillus species. Although the microorganisms used in
      MBCPs are subject to regulation in Canada under the Canadian Environmental
      Protection Act, the products themselves are not. Unlike other types of microbial
      products such as probiotics and biopesticides, the use, manufacture and quality
      parameters of MBCPs in Canada and other countries are poorly defined and not
      specifically subject to any required standards. Due to their complexity and
      nature, these products feature unique quality challenges. We noted the existing
      MBCPs we analyzed vary vastly in quality; external microbial contaminants,
      viability of the spores and the biocompatibility of the ingredients are issues
      that greatly affect product quality. A proper taxonomic identification of the
      bacterial species used also seems to be a major challenge for a number of
      manufacturers. A good understanding of the mechanisms governing these quality
      challenges and the adoption of good practices for the cultivation, harvesting,
      formulation, and manufacture of these types of products are essential for
      achieving high-quality performance standards.

PMID- 29066410
TI  - Probabilistic assessment method of the non-monotonic dose-responses-Part II:
      Robustness assessment.
AB  - In a previous study, we presented a new method that uses a large-scale sampling
      system to probabilistically assess non-monotonic dose-response curves. The
      statistical plausibility of the characterization was governed by the probability
      of the dominant category, but gave no information about the specific robustness
      of the curve. In this paper we propose an improvement to the method by
      integrating a scoring system based on 4 criteria which can be used to assess the
      slope robustness of each of the 10,000 sampled curves. The distribution criterion
      which assesses the number of doses forming a slope, the intensity criterion which
      assesses the amplitude of the response, and the minimum and maximum confirmation
      criteria which increase the certainty that the response is present. The
      probabilistic method was tested on 294 dose-response curves taken from 2
      databases and 2 other methodologies currently proposed. A total of 544 dose
      response curves have been processed. The developed method offers a concrete and
      probabilistic characterization of the type of curve analyzed. It evaluates its
      statistical plausibility and its robustness according to its sampling curves.
      This method is applicable to all types of data (continuous and discrete) and all
      experimental curves starting from theoretically 3 doses at least.

PMID- 29066412
TI  - Schisandrol B promotes liver regeneration after partial hepatectomy in mice.
AB  - Liver regeneration is a vital process of recovery after liver damage, which is a
      promising clinical strategy after partial hepatectomy (PHx). Schisandrol B
      (SolB), one of the bioactive ingredients from Schisandra sphenanthera, displays
      significant hepato-protection effects against drug-induced liver injure in mice.
      However, the effect of SolB on liver regeneration after PHx remains unclear.
      Here, we showed that SolB treatment promoted liver mass restoration and increased
      the number of proliferative hepatocytes following PHx. SolB treatment
      significantly improved the levels of growth factors (HGF and EGF) and cytokines
      (IL-6), which further activated STAT3/Akt/MAPK signaling pathways and induced the
      expression of several the protein of cell cycle core. Overall, this study is the
      first to demonstrate the role of SolB in promoting liver regeneration during PHx
      challenge, which provide a clinically relevant argument for using SolB to
      facilitate liver recovery after undergoing PHx or liver transplantation.

PMID- 29066413
TI  - Effects of incretin-based therapies on renal function.
AB  - Glucagon like peptide-1 receptor agonists and dipeptidyl peptidase-IV inhibitors
      (collectively termed incretin-based therapies) represent two of the most widely
      used classes of antidiabetic drugs. These compounds exert their beneficial
      effects on carbohydrate metabolism through the activation of specific glucagon
      like peptide-1 receptors in various organs. Accumulating evidence suggests that
      glucagon like peptide-1 receptor agonists and dipeptidyl peptidase-IV inhibitors
      also affect renal function in both glucagon like peptide-1 receptor-dependent and
      independent manner. However, the clinical significance of these observations
      remains indeterminate. In this review, we summarize the available preclinical and
      clinical data on the effects of incretin-based therapies on renal function
      indices and discuss their relevance in everyday clinical practise.

PMID- 29066411
TI  - Gallic acid, a natural polyphenol, protects against tert-butyl hydroperoxide-
      induced hepatotoxicity by activating ERK-Nrf2-Keap1-mediated antioxidative
      response.
AB  - Gallic acid (GA), a natural polyphenol, has been shown to exert a variety of
      heath promoting effects. We herein investigated the critical role of nuclear
      factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response in the
      protection of GA against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity
      in L02 cells. Pretreatment of GA prevented the hepatocytotoxicity induced by t
      BHP, as evidenced by the facts that GA suppressed t-BHP-induced cytotoxicity and
      reactive oxygen species (ROS) generation. GA induced nuclear translocation of
      Nrf2 along with expression of target proteins, including heme oxygenase-1 (HO-1)
      and glutamate cysteine ligase catalytic modify subunit (GCLC), and increased
      intracellular glutathione (GSH) content. Additionally, GA induced phosphorylated
      activation of extracellular regulated kinase (ERK), and ERK inhibitor PD98059
      partially decreased GA-induced hepatoprotection, and downregulated the increased
      protein expressions of Nrf2, GCLC and HO-1 induced by GA. Interestingly, we found
      that GA could enhance the thermal stability of Keap1, which indicated the
      potential interaction between GA and Keap1. Furthermore, molecular docking
      indicated that GA possibly competed with Nrf2 for binding to Keap1. Collectively,
      GA effectively protects against t-BHP-induced hepatotoxicity via inducing
      ERK/Nrf2-mediated antioxidative signaling pathway. Meanwhile, GA disturbs protein
      protein interaction between Keap1 and Nrf2 which might also contribute to nuclear
      translocation of Nrf2.

PMID- 29066414
TI  - Z-505 hydrochloride ameliorates chemotherapy-induced anorexia in rodents via
      activation of the ghrelin receptor, GHSR1a.
AB  - Despite its therapeutic advantages, chemotherapy with anti-cancer drugs can cause
      adverse effects, including anorexia and weight loss. Although most patients with
      cancer suffer from anorexia during chemotherapy, resulting in the need to suspend
      or cease treatment and thereby worsening prognosis, treatment options for
      anorexia remain limited. Ghrelin is an orexigenic hormone that has been proposed
      to prevent anorexia. To investigate the potential of ghrelin receptor agonists,
      synthetic small-molecule compounds, as preventive therapies for chemotherapy
      induced anorexia, we studied the effects of Z-505 hydrochloride (Z-505), a new
      oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, in cisplatin- and
      5-fluorouracil (5-FU)-induced anorexia animal models. The agonistic activity of Z
      505 was examined using calcium flux assays in Chinese hamster ovary (CHO-K1)
      cells stably expressing rat or mouse GHSR1a. Z-505 showed agonistic activity for
      rat GHSR1a and mouse GHSR1a, with a half maximal effective concentration (EC50)
      of 2.08nM and 5.46nM, respectively. In a cisplatin-induced anorexia rat model,
      administration of Z-505 (30, 100 or 300mg/kg, p.o., once daily) significantly
      improved the cisplatin-induced reduction in food intake and body weight. In
      addition, treatment with Z-505 (100 or 300mg/kg, p.o., once daily) prevented the
      5-FU-induced decrease in food intake and body weight in the 5-FU-induced mouse
      model. Our results demonstrate that Z-505 ameliorates cisplatin- and 5-FU-induced
      anorexia through the activation of the ghrelin receptor, GHSR1a, suggesting its
      usefulness in the preventive treatment of anorexia during chemotherapy.

PMID- 29066415
TI  - Inotropic effect of NCX inhibition depends on the relative activity of the
      reverse NCX assessed by a novel inhibitor ORM-10962 on canine ventricular
      myocytes.
AB  - Na+/Ca2+ exchanger (NCX) is the main Ca2+ transporter in cardiac myocytes. Its
      inhibition could be expected to exert positive inotropic action by accumulation
      of cytosolic Ca2+ ([Ca2+]i). However, we have observed only a marginal positive
      inotropic effect upon selective inhibition of NCX, which was enhanced when
      forward activity was facilitated. Here we attempted to clarify the underlying
      mechanism of the limited inotropic action of selective NCX inhibition by a novel
      inhibitor ORM-10962 on canine ventricular myocytes. 1uM ORM-10962 reduced the
      Ca2+ content of sarcoplasmic reticulum (SR) when the reverse NCX was favoured,
      while SR Ca2+ content was increased by ORM-10962 under conditions favouring the
      forward activity, like elevation of [Ca2+]i. L-type Ca2+ current (ICa) was not
      affected by 1uM ORM-10962 in the absence of SR Ca2+ release, while ICa was
      suppressed by ORM-10962 during normal Ca2+ cycling. The apparent degree of
      forward NCX inhibition was dependent on the elevation of [Ca2+]i, suggesting that
      an increased driving force of forward NCX can also limit the accumulation of
      [Ca2+i]. We concluded that in healthy myocardium the possible positive inotropic
      potential of NCX inhibition is considerably weaker than it was expected earlier
      by theoretical assumptions. The underlying mechanism may involve the
      autoregulation of Ca2+ handling and/or the preserved inducibility of forward NCX
      by high [Ca2+]i. This limitation of selective NCX inhibition seen in undiseased
      myocardium requires further studies in failing heart, which may allow correct
      evaluation of the potential therapeutic value of selective NCX inhibitors in the
      treatment of heart failure.

PMID- 29066416
TI  - A novel Danshensu/tetramethylpyrazine derivative induces vasorelaxation on rat
      aorta and exerts cardioprotection in dogs.
AB  - ADTM, a previously reported novel Danshensu (DSS)/tetramethylpyrazine (TMP)
      derivative with cardioprotective and antiplatelet aggregative effects, is a
      promising therapeutic candidate for ischemic heart diseases. In the present
      study, ADTM increased coronary blood flow and protected myocardium against
      ischemic injury in dogs. In addition, the relaxing effect of ADTM on rat thoracic
      aorta and its underlying mechanisms were examined. ADTM relaxed KCl- and
      phenylephrine-precontracted arotic rings in a concentration-dependent manner. The
      relaxation by ADTM was greater than that by DSS, TMP and the mixture of DSS and
      TMP. ADTM induced endothelium-independent relaxation, which couldn't be abolished
      by removal of endothelium and the preincubation with inhibitors of nitric oxide
      synthase (L-NAME) and guanylate cyclase (ODQ). Potassium channel blockers
      including tetraethylammonium, BaCl2 and glibenclamide failed to inhibit the
      relaxation by ADTM. In addition, cyclooxygenase (COX), muscarine receptor and
      beta-adrenoceptor were not involved in ADTM-induced vasorelaxation. ADTM
      inhibited contraction induced by CaCl2 and phenylephrine in Ca2+-free buffer,
      suggesting that ADTM inhibited both extracellular Ca2+ influx and intracellular
      Ca2+ release. Taken together, the vasorelaxation of ADTM may be possibly involved
      in its cardioprotection. ADTM may serve as a promising candidate for the
      treatment of ischemic heart diseases.

PMID- 29066418
TI  - Beneficial effects of resistance training on the protein profile of the calcaneal
      tendon during aging.
AB  - The calcaneal tendon (CT) is the most commonly injured tendon in the human body.
      Moreover, with advancing age, the amount of damage increases further. Resistance
      training (RT) could be used to minimize such damages. The aim of the present
      study was to obtain the identification, detailed protein cataloging and
      biochemical characterization based on the effects of the aging process and the RT
      in CT of rats. The analysis by liquid chromatography tandem-mass spectrometry
      showed 142 distinct proteins, however, only 29 proteins met the inclusion
      criteria and were analyzed. Aging causes a reduction in the abundance of seven
      proteins related to extracellular matrix organization, biological regulation and
      cellular processes. However, RT promoted the positive regulation of proteins
      important for the maintenance of healthy tendons: seven proteins in young trained
      and two in older trained group. This study contributes to a better understanding
      of molecular aspects of the tendon. The down regulation of proteins linked to
      mechanical function and extracellular matrix remodeling of the tendon during
      aging can contribute to the increase of injury and weakness in the tendon.
      Nevertheless, RT proved to be a tool to prevent these adverse effects during
      aging by increasing proteins involved in the functionality of the tendon.

PMID- 29066417
TI  - Combined aerosolized Toll-like receptor ligands are an effective therapeutic
      agent against influenza pneumonia when co-administered with oseltamivir.
AB  - Influenza pneumonia remains a common and debilitating viral infection despite
      vaccination programs and antiviral agents developed for prophylaxis and
      treatment. The neuraminidase inhibitor oseltamivir is frequently prescribed for
      established influenza A virus infections, but the emergence of neuraminidase
      inhibitor resistant viruses, a brief therapeutic window and competing diagnoses
      complicate its use. PUL-042 is a clinical stage, aerosol drug comprised of
      synthetic ligands for Toll-like receptor (TLR) 2/6 and TLR 9. This host-targeted,
      innate immune stimulant broadly protects against bacterial, fungal and viral
      pneumonias, including those caused by influenza, when given prophylactically to
      animals. This study evaluated the therapeutic antiviral effects of PUL-042
      against established influenza A pneumonia, when given alone or in combination
      with oseltamivir. Mice were treated with PUL-042 aerosol, oseltamivir or both at
      varying time points before or after challenge with influenza pneumonia. Treating
      established, otherwise lethal influenza A pneumonia (>1 LD100) with multiple
      inhaled doses of PUL-042 aerosol plus oral oseltamivir resulted in greater mouse
      survival than treatment with either drug alone. Single agent PUL-042 also
      protected mice against established infections following challenges with lower
      viral inocula (approximately 1 LD20). Aerosolized oseltamivir further enhanced
      survival when co-delivered with PUL-042 aerosol. The prophylactic and therapeutic
      benefits of PUL-042 were similar against multiple strains of influenza virus. In
      vitro influenza challenge of human HBEC3kt lung epithelial cells revealed PUL-042
      induced protection against infection that was comparable to that observed in
      vivo. These studies offer new insights into means to protect susceptible
      populations against influenza A pneumonia.

PMID- 29066419
TI  - Effect of stem cell niche elasticity/ECM protein on the self-beating
      cardiomyocyte differentiation of induced pluripotent stem (iPS) cells at
      different stages.
AB  - : Stem cell-based myocardial regeneration therapies have emerged as alternative
      strategies to heart transplantation for serious heart diseases, but autologous
      beating mature cardiomyocytes are not available. Here we investigated the effect
      of culture substrates on the cardiomyocyte differentiation of induced pluripotent
      stem cells (iPSs) in vitro by separately evaluating the following continuous
      three steps: (1) cardiac marker gene expression, (2) contractile gene expression
      and self-beating, and (3) beating duration. To this end, we used iPS cells to
      study the cardiac differentiation, and neonatal rat cardiomyocytes (NCMs) to
      study beating behavior. These cells were cultured on substrates with different
      natures, i.e., an elastic substrate (Es) with the modulus of 9, 20, or 180 kPa,
      and hard tissue culture polystyrene dishes (TCPS) coated with collagen type I
      (Col), gelatin (Gel), or fibronectin (FN). The results revealed that the
      effective niches in each step were very different. The cardiac marker gene
      (GATA4, Tbx5, MEF2C) expression of iPSs at the 1st step was very high on the TCPS
      coated with FN or Gel, whereas on the FN-coated Es (especially with the 9 kPa
      modulus), the undifferentiated marker gene (Nanog) expression of iPSs was
      maintained. The expression of the contractile genes alpha-MHC, TnC1, and TnT2 and
      the self-beating (the 2nd step) of the NCMs were high on FN-coated TCPS and Col
      coated Es. The 3rd step (beating duration) of the NCMs was effective on the Es,
      and at 21 days both the iPSs and NCMs stopped beating on the TCPS but were still
      beating on the Es. Overall, cardiac differentiation 'preferred' ECM-rigid culture
      substrates, and beating-behavior 'preferred' Col-soft culture substrates. These
      results are important for understanding and designing cardiac differentiation
      niches for regenerative medicine, and they suggest that a single culture
      substrate is not suitable for preparing self-beating cardiomyocytes. STATEMENT OF
      SIGNIFICANCE: The transplantation of beating cardiomyocytes (BCMs) is expected to
      be made more effective for serious heart diseases. The identification of the
      appropriate engineering processes and suitable culture substrates for inducing
      stem cell differentiation into BCMs is thus indispensable. The differentiation
      can be divided into three major processes, the cardiac differentiation step, the
      beating-induction step and the beating-duration step. A protocol with the higher
      efficiency in all of the steps must be useful. In this study, we separately
      evaluated the effect of culture substrates at each three step. We clarified that
      the biological and the physical properties of the culture substrates required at
      these steps were different. We found useful criteria for effective cardiac cell
      niche systems design.

PMID- 29066420
TI  - Cu-doping of calcium phosphate bioceramics: From mechanism to the control of
      cytotoxicity.
AB  - : In this study, the Cu-doping mechanism of Biphasic Calcium Phosphate (BCP) was
      thoroughly investigated, as was its ionic release behavior, in order to elucidate
      cytotoxicity features of these bioceramics. BCP are composed of hydroxyapatite
      (Ca10(PO4)6(OH)2) and beta-TCP (Ca3(PO4)2). The two phases present two different
      doping mechanisms. Incorporation into the beta-TCP structure is achieved at
      around 700  degrees C thanks to a substitution mechanism leading to the Cu-doped
      Ca3-xCux(PO4)2 compound. Incorporation into the HAp structure is achieved thanks
      to an interstitial mechanism that is limited to a Cu-poor HAp phase for
      temperatures below 1100  degrees C (Ca10Cux(PO4)6(OH)2-2xO2x with x < 0.1). Above
      1100  degrees C, the same interstitial mechanism leads to the formation of a Cu
      rich HAp mixed-valence phase (Ca10Cu2+xCu+y(PO4)6(OH)2-2x-yO2x+y with x + y ~
      0.5). The formation of both high-temperature Cu-doped alpha-TCP and Cu3(PO4)2
      phases above 1100  degrees C induces a transformation into the Cu-rich HAp phase
      on cooling. The linear OCuO oxocuprate entity was confirmed by EXAFS
      spectroscopy, and the mixed Cu+/Cu2+ valence was evidenced by XPS analyses. Ionic
      releases (Cu+/Cu2+, Ca2+, PO42- and OH-) in water and in simulated body media
      were investigated on as-synthesized ceramics to establish a pretreatment before
      biological applications. Finally the cytotoxicity of pretreated disks was
      evaluated, and results confirm that Cu-doped BCP samples are promising
      bioceramics for bone substitutes and/or prosthesis coatings. STATEMENT OF
      SIGNIFICANCE: Biphasic Calcium Phosphates (BCP) are bioceramics composed of
      hydroxyapatite (HAp, Ca10(PO4)6(OH)2) and beta-Tricalium Phosphate (beta-TCP,
      Ca3(PO4)2). Because their chemical and mineral composition closely resembles that
      of the mineral component of bone, they are potentially interesting candidates for
      bone repair surgery. Doping can advantageously be used to improve their
      biological behaviors; however, it is important to describe the doping mechanism
      of BCP thoroughly in order to fully appraise the benefit of the doping process.
      The present paper scrutinizes in detail the incorporation of copper cation in
      order to correctly interpret the behavior of the Cu-doped bioceramic in
      biological fluid. The understanding of the copper doping mechanism, related to
      doping mechanism of others 3d-metal cations, makes it possible to explain the
      rates and kinetic of release of the dopant in biological medium. Finally, the
      knowledge of the behavior of the copper doped ceramic in biological environment
      allowed the tuning of its cytotoxicity properties. The present study resulted on
      pre-treated ceramic disks which have been evaluated as promising biocompatible
      ceramic for bone substitute and/or prosthesis coating: good adherence of bone
      marrow cells with good cell viability.

PMID- 29066421
TI  - Caregiver Input to Optimize the Design of a Pediatric Care Planning Guide for
      Rehabilitation: Descriptive Study.
AB  - BACKGROUND: Caregiver input has informed the design of a valid electronic patient
      reported outcome (PRO) measure for use in pediatric rehabilitation. This proxy
      assessment may be further developed to expedite and enhance patient-centered care
      planning processes, but user input is first needed to finalize the core
      requirements that will guide its design. OBJECTIVE: The objective of this study
      was to examine the feasibility of a stepwise process for building on a baseline
      assessment of young children's participation in activities to develop a care plan
      relevant to pediatric rehabilitation. METHODS: A cross-sectional descriptive
      study design was employed using qualitative methods. Data were collected via Web
      based technology and by telephone. Twenty-five caregivers of young children (9
      with developmental delays, 16 without delays) and between 1 and 7 years were
      recruited from a subsample of parents who had previously enrolled in a Web-based
      validation of a PRO on children's participation and provided consent for future
      contact. Each caregiver completed a demographic questionnaire and Young
      Children's Participation and Environment Measure (YC-PEM) online, followed by a
      20- to 60-min semistructured and audiotaped phone interview to review and build
      upon PRO results as summarized in an electronic report. Interview data were
      content coded to the interview guide and reviewed by multiple research staff to
      estimate feasibility according to stepwise completion rates, perceptions of
      difficulty in step completion, and perceptions of overall utility. RESULTS: Half
      of the participants in the final study sample (N=25) fully completed a stepwise
      process of building on their baseline PRO assessment to develop an initial care
      plan for their child. In most cases, similar stepwise completion rates and trends
      in the approaches taken for step completion were found regardless of the child's
      disability status. However, more parents of children with disabilities reported
      difficulties in rank ordering their priorities for change and identified child
      focused strategies for goal attainment. Nearly 77% (19/25) of users were willing
      to use the process to develop and communicate intervention priorities and
      strategies with professionals, family, and friends. CONCLUSIONS: Results informed
      revisions to the care planning guide before usability and feasibility testing of
      an initial Web-based prototype that is now underway.

PMID- 29066423
TI  - Examining Motivations to Play Pokemon GO and Their Influence on Perceived
      Outcomes and Physical Activity.
AB  - BACKGROUND: Pokemon GO is the most played augmented reality game in history. With
      more than 44 million players at the peak of its popularity, the game has sparked
      interest on its effects on the young population's health. OBJECTIVE: This pilot
      study examined motivations to start playing Pokemon GO among a sample of US
      college students, and how motivations were associated with perceived outcomes of
      the playing experience and physical activity derived while playing. METHODS: In
      November 2016, we asked a sample of 47 US college students (all Pokemon GO
      players) to complete online surveys and install an ecological momentary
      assessment (EMA) tool and step counter on their smartphones. The EMA tool
      prompted a set of questions on playing behavior and physical activity, 3 times
      per day (12:00 PM, 7:00 PM, and 10:00 PM), for 7 days. We used a factorial
      analysis to identify 3 distinctive groups of players based on their motivations
      to start playing Pokemon GO. We tested differences across motivation groups
      related to 5 unique outcomes using 1-way analysis of variance. RESULTS: We
      extracted 3 interpretable factors from the clustering of motivations to start
      playing Pokemon GO: Pokemon and video game fans (n=26, 55% of the sample),
      physical activity seekers (n=8, 17%), and curious & social (n=13, 28%). The
      clusters differed significantly on the enjoyment of different aspects of the
      game, particularly battling, discovering new places, and meeting new people, as
      well as differences in agreement that playing improved mood and made them more
      social. Days when playing Pokemon GO were associated with higher number of steps
      reported at the end of the day, especially among physical activity seekers, but
      also for Pokemon and video game fans. All groups perceived traffic as a major
      threat to playing. CONCLUSIONS: Days during which Pokemon GO was played were
      positively associated with a set of beneficial health behaviors, including higher
      physical activity levels, more socialization, and better mood. Results, however,
      depended on personal motivations and expectations when joining the game. These
      results highlight the importance of taking motivation into account when
      attempting to extract conclusions from the Pokemon GO phenomenon to enhance
      future exergames' designs or health interventions.

PMID- 29066424
TI  - Adopting Telemedicine for the Self-Management of Hypertension: Systematic Review.
AB  - BACKGROUND: Hypertension is a chronic condition that affects adults of all ages.
      In the United States, 1 in 3 adults has hypertension, and about half of the
      hypertensive population is adequately controlled. This costs the nation US $46
      billion each year in health care services and medications required for treatment
      and missed workdays. Finding easier ways of managing this condition is key to
      successful treatment. OBJECTIVE: A solution to reduce visits to physicians for
      chronic conditions is to utilize telemedicine. Research is limited on the effects
      of utilizing telemedicine in health care facilities. There are potential benefits
      for implementing telemedicine programs with patients dealing with chronic
      conditions. The purpose of this review was to weigh the facilitators against the
      barriers for implementing telemedicine. METHODS: Searches were methodically
      conducted in the Cumulative Index to Nursing and Allied Health Literature
      Complete (CINAHL Complete) via Elton B Stephens Company (EBSCO) and PubMed (which
      queries MEDLINE) to collect information about self-management of hypertension
      through the use of telemedicine. RESULTS: Results identify facilitators and
      barriers corresponding to the implementation of self-management of hypertension
      using telemedicine. The most common facilitators include increased access,
      increase in health and quality, patient knowledge and involvement, technology
      growth with remote monitoring, cost-effectiveness, and increased
      convenience/ease. The most prevalent barriers include lack of evidence, self
      management difficult to maintain, no long-term results/more areas to address, and
      long-term added workload commitment. CONCLUSIONS: This review guides health care
      professionals in incorporating new practices and identifying the best methods to
      introduce telemedicine into their practices. Understanding the facilitators and
      barriers to implementation is important, as is understanding how these factors
      will impact a successful implementation of telemedicine in the area of self
      management of hypertension.

PMID- 29066422
TI  - Preliminary Findings of a Technology-Delivered Sexual Health Promotion Program
      for Black Men Who Have Sex With Men: Quasi-Experimental Outcome Study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) disproportionately affects black
      men who have sex with men (MSM), yet there are few evidence-based interventions
      specifically designed for black MSM communities. In response, the authors created
      Real Talk, a technology-delivered, sexual health program for black MSM.
      OBJECTIVE: The objective of our study was to determine whether Real Talk
      positively affected risk reduction intentions, disclosure practices, condom use,
      and overall risk reduction sexual practices. METHODS: The study used a quasi
      experimental, 2-arm methodology. During the first session, participants completed
      a baseline assessment, used Real Talk (intervention condition) or reviewed 4
      sexual health brochures (the standard of care control condition), and completed a
      10-minute user-satisfaction survey. Six months later, participants from both
      conditions returned to complete the follow-up assessment. RESULTS: A total of 226
      participants were enrolled in the study, and 144 completed the 6-month follow-up.
      Real Talk participants were more likely to disagree that they had intended in the
      last 6 months to bottom without a condom with a partner of unknown status (mean
      difference=-0.608, P=.02), have anal sex without a condom with a positive man who
      was on HIV medications (mean difference=-0.471, P=.055), have their partner pull
      out when bottoming with a partner of unknown HIV status (mean difference=-0.651,
      P=.03), and pull out when topping a partner of unknown status (mean difference=
      0.644, P=.03). Real Talk participants were also significantly more likely to
      disagree with the statement "I will sometimes lie about my HIV status with people
      I am going to have sex with" (mean difference=-0.411, P=.04). In terms of
      attitudes toward HIV prevention, men in the control group were significantly more
      likely to agree that they had less concern about becoming HIV positive because of
      the availability of antiretroviral medications (mean difference=0.778, P=.03) and
      pre-exposure prophylaxis (PReP) (mean difference=0.658, P=.05). There were,
      however, no significant differences between Real Talk and control participants
      regarding actual condom use or other risk reduction strategies. CONCLUSIONS: Our
      findings suggest that Real Talk supports engagement on HIV prevention issues. The
      lack of behavior findings may relate to insufficient study power or the fact that
      a 2-hour, standalone intervention may be insufficient to motivate behavioral
      change. In conclusion, we argue that Real Talk's modular format facilitates its
      utilization within a broader array of prevention activities and may contribute to
      higher PReP utilization in black MSM communities.

PMID- 29066425
TI  - Mobile Technology Use Across Age Groups in Patients Eligible for Cardiac
      Rehabilitation: Survey Study.
AB  - BACKGROUND: Emerging evidence indicates mobile technology-based strategies may
      improve access to secondary prevention and reduce risk factors in cardiac
      patients. However, little is known about cardiac patients' use of mobile
      technology, particularly for health reasons and whether the usage varies across
      patient demographics. OBJECTIVE: This study aimed to describe cardiac patients'
      use of mobile technology and to determine variations between age groups after
      adjusting for education, employment, and confidence with using mobile technology.
      METHODS: Cardiac patients eligible for attending cardiac rehabilitation were
      recruited from 9 hospital and community sites across metropolitan and rural
      settings in New South Wales, Australia. Participants completed a survey on the
      use of mobile technology devices, features used, confidence with using mobile
      technology, willingness and interest in learning, and health-related use.
      RESULTS: The sample (N=282) had a mean age of 66.5 (standard deviation [SD] 10.6)
      years, 71.9% (203/282) were male, and 79.0% (223/282) lived in a metropolitan
      area. The most common diagnoses were percutaneous coronary intervention (33.3%,
      94/282) and myocardial infarction (22.7%, 64/282). The majority (91.1%, 257/282)
      used at least one type of technology device, 70.9% (200/282) used mobile
      technology (mobile phone/tablet), and 31.9% (90/282) used all types. Technology
      was used by 54.6% (154/282) for health purposes, most often to access information
      on health conditions (41.4%, 117/282) and medications (34.8%, 98/282). Age had an
      important independent association with the use of mobile technology after
      adjusting for education, employment, and confidence. The youngest group (<56
      years) was over 4 times more likely to use any mobile technology than the oldest
      (>69 years) age group (odds ratio [OR] 4.45, 95% CI 1.46-13.55), 5 times more
      likely to use mobile apps (OR 5.00, 95% CI 2.01-12.44), and 3 times more likely
      to use technology for health-related reasons (OR 3.31, 95% CI 1.34-8.18).
      Compared with the older group, the middle age group (56-69 years) was more than
      twice as likely to use any mobile technology (OR 2.42, 95% CI 1.27-4.59) and
      mobile technology for health-related purposes (OR 1.92, 95% CI 1.04-3.53).
      Participants who had completed high school were twice as likely to use mobile
      technology (OR 2.62, 95% CI 1.45-4.70), mobile apps (OR 2.05, 95% CI 1.09-3.84),
      and mobile technology for health-related reasons (OR 5.09, 95% CI 2.89-8.95) than
      those who had not completed high school. Associations were also present between
      participants living in metropolitan areas and mobile technology use (OR 1.07, 95%
      CI 1.07-4.24) and employment and mobile app use (OR 2.72, 95% CI 1.44-5.140).
      CONCLUSIONS: Mobile technology offers an important opportunity to improve access
      to secondary prevention for cardiac patients, particularly when modified to suit
      subgroups. High levels of mobile technology use and health motivation need to be
      harnessed for secondary prevention.

PMID- 29066427
TI  - The Adoption of Social Media to Recruit Participants for the Cool Runnings
      Randomized Controlled Trial in Australia.
AB  - BACKGROUND: Using social media to recruit specific populations for research
      studies is gaining popularity. Given that mothers of young children are the most
      active on social media, and young children are the most at risk of preventable
      burn injuries, social media was used to recruit mothers of young children to a
      burn prevention intervention. OBJECTIVE: The aim of this paper was to describe
      the social media recruitment methods used to enroll mothers of young children to
      the app-based burn prevention intervention Cool Runnings. METHODS: Participants
      were recruited via paid Facebook and Instagram advertisements to a 2-group,
      parallel, single-blinded, randomized controlled trial (RCT). The advertisements
      were targeted at women 18 years and older, living in Queensland, Australia, with
      at least 1 child aged 5 to 12 months at the time of recruitment. RESULTS: Over
      the 30-day recruitment period from January to February 2016, Facebook and
      Instagram advertisements reached 65,268 people, generating 2573 link clicks, 1161
      app downloads, and 498 enrolled participants to the Cool Runnings RCT. The cost
      per enrolled participant was Aus $13.08. Saturdays were the most effective day of
      the week for advertising results. The most popular time of day for enrolments was
      between 5 to 11 PM. This recruitment strategy campaign resulted in a broad reach
      of participants from regional, rural, and remote Queensland. Participants were
      representative of the population in regard to age and education levels.
      CONCLUSIONS: To our knowledge, this is the first use of social media recruitment
      for an injury prevention campaign. This recruitment method resulted in the rapid
      and cost-effective recruitment of participants with social, geographic, and
      economic diversity that were largely representative of the population.

PMID- 29066426
TI  - Techniques for Improving Communication of Emotional Content in Text-Only Web
      Based Therapeutic Communications: Systematic Review.
AB  - BACKGROUND: Web-based typed exchanges are increasingly used by professionals to
      provide emotional support to patients. Although some empirical evidence exists to
      suggest that various strategies may be used to convey emotion during Web-based
      text communication, there has been no critical review of these data in patients
      with chronic conditions. OBJECTIVES: The objective of this review was to identify
      the techniques used to convey emotion in written or typed Web-based communication
      and assess the empirical evidence regarding impact on communication and
      psychological outcomes. METHODS: An electronic search of databases, including
      MEDLINE, CINAHL, PsycINFO, EMBASE, and the Cochrane Library was conducted to
      identify literature published from 1990 to 2016. Searches were also conducted
      using Google Scholar, manual searching of reference lists of identified papers
      and manual searching of tables of contents for selected relevant journals. Data
      extraction and coding were completed by 2 reviewers (10.00% [573/5731] of
      screened papers, at abstract/title screening stage; 10.0% of screened [69/694]
      papers, at full-text screening stage). Publications were assessed against the
      eligibility criteria and excluded if they were duplicates, were not published in
      English, were published before 1990, referenced animal or nonhuman subjects, did
      not describe original research, were not journal papers, or did not empirically
      test the effect of one or more nonverbal communication techniques (for eg,
      smileys, emoticons, emotional bracketing, voice accentuation, trailers
      [ellipsis], and pseudowords) as part of Web-based or typed communication on
      communication-related variables, including message interpretation, social
      presence, the nature of the interaction (eg, therapeutic alliance), patient
      perceptions of the interaction (eg, participant satisfaction), or psychological
      outcomes, including depression, anxiety, and distress. RESULTS: A total of 6902
      unique publications were identified. Of these, six publications met the
      eligibility criteria and were included in a narrative synthesis. All six studies
      addressed the effect of smileys or emoticons on participant responses, message
      interpretation, or social presence of the writer. None of these studies
      specifically targeted chronic conditions. It was found that emoticons were more
      effective in influencing the emotional impact of a message than no cue and that
      smileys and emoticons were able to convey a limited amount of emotion. No studies
      addressed other techniques for conveying emotion in written communication. No
      studies addressed the effects of any techniques on the nature of the interaction
      (eg, therapeutic alliance), patient perceptions of the interaction (eg,
      participant satisfaction), or psychological outcomes (depression, anxiety, or
      distress). CONCLUSIONS: There is a need for greater empirical attention to the
      effects of the various proposed techniques for conveying emotion in Web-based
      typed communications to inform health service providers regarding best-practice
      communication skills in this setting.

PMID- 29066428
TI  - Willingness to Pay for Elderly Telecare Service Using the Internet and Digital
      Terrestrial Broadcasting.
AB  - BACKGROUND: In Japan over the past few years, more attention has been focused on
      unnoticed solitary death in the context of an aging society and the trend toward
      nuclear family. A number of institutions and companies have implemented a
      prevention measure with digital terrestrial broadcasting telecare services for
      the elderly: Hokkaido University; TV-Asahi Corporation; Hitachi, Ltd; Iwamizawa
      City; Hokkaido Television Broadcasting Co, Ltd; and Hamanasu Information Co, Ltd.
      Although this system is provided free of charge as a demonstration test,
      determining the appropriate price for the service is required for its sustainable
      operation. OBJECTIVE: The aim of this study was to quantify individual
      willingness to pay (WTP) so as to test the tenability of digital terrestrial
      broadcasting service for elderly telecare. METHODS: We used the contingent
      valuation method (CVM) to estimate the WTP for this service among 305 citizens
      (valid response rate 76.0%) living in Japan. A questionnaire survey was conducted
      for people aged 18 to 100 years according to Japanese age distribution from
      September 2016. To elicit WTP, we adopted a double-bound dichotomous choice
      method to ask the respondents whether they agree or disagree with the price we
      offered. RESULTS: The median WTP for this service's monthly fee is estimated to
      be 431 JPY (approximately US $3.7). The finding suggests that gender (0.66,
      P=.01), health consciousness (1.08, P=.01), willingness to use (2.38, P<.001),
      and seeing others less than once a week (1.00, P=.06) made a positive effect on
      WTP. CONCLUSIONS: We conclude that reliable WTP was elicited by CVM based on an
      Internet survey. Calculated median WTP for digital terrestrial broadcasting
      service for elderly telecare was 431 JPY (approximately US $3.7). In the analysis
      of factors that affect WTP, constant factors, log-bid, health consciousness,
      gender, see others less than one time for week, and willingness to use made
      positive effect to probability of acceptance. In comparison of WTP in different
      groups, age groups showed that WTP of the elderly group was higher than WTP of
      the middle age group and younger age group. However, WTP surveys need to be
      carefully conducted to minimize the sampling bias and allocate accurate structure
      of gender distribution.

PMID- 29066430
TI  - David Oliver: Binary truths don't help health policy debate.

PMID- 29066429
TI  - What is eHealth (6)? Development of a Conceptual Model for eHealth: Qualitative
      Study with Key Informants.
AB  - BACKGROUND: Despite rapid growth in eHealth research, there remains a lack of
      consistency in defining and using terms related to eHealth. More widely cited
      definitions provide broad understanding of eHealth but lack sufficient conceptual
      clarity to operationalize eHealth and enable its implementation in health care
      practice, research, education, and policy. Definitions that are more detailed are
      often context or discipline specific, limiting ease of translation of these
      definitions across the breadth of eHealth perspectives and situations. A
      conceptual model of eHealth that adequately captures its complexity and potential
      overlaps is required. This model must also be sufficiently detailed to enable
      eHealth operationalization and hypothesis testing. OBJECTIVE: This study aimed to
      develop a conceptual practice-based model of eHealth to support health
      professionals in applying eHealth to their particular professional or discipline
      contexts. METHODS: We conducted semistructured interviews with key informants
      (N=25) from organizations involved in health care delivery, research, education,
      practice, governance, and policy to explore their perspectives on and experiences
      with eHealth. We used purposeful sampling for maximum diversity. Interviews were
      coded and thematically analyzed for emergent domains. RESULTS: Thematic analyses
      revealed 3 prominent but overlapping domains of eHealth: (1) health in our hands
      (using eHealth technologies to monitor, track, and inform health), (2)
      interacting for health (using digital technologies to enable health communication
      among practitioners and between health professionals and clients or patients),
      and (3) data enabling health (collecting, managing, and using health data). These
      domains formed a model of eHealth that addresses the need for clear definitions
      and a taxonomy of eHealth while acknowledging the fluidity of this area and the
      strengths of initiatives that span multiple eHealth domains. CONCLUSIONS: This
      model extends current understanding of eHealth by providing clearly defined
      domains of eHealth while highlighting the benefits of using digital technologies
      in ways that cross several domains. It provides the depth of perspectives and
      examples of eHealth use that are lacking in previous research. On the basis of
      this model, we suggest that eHealth initiatives that are most impactful would
      include elements from all 3 domains.

PMID- 29066431
TI  - Running causes knee osteoarthritis: myth or misunderstanding.

PMID- 29066432
TI  - Health benefits of tennis.

PMID- 29066433
TI  - Gait retraining: out of the lab and onto the streets with the benefit of
      wearables.

PMID- 29066434
TI  - Ride report: mobile app user guide.

PMID- 29066435
TI  - StrongLifts 5*5 Workout: mobile app user guide.

PMID- 29066436
TI  - Interleukin-6 and the Risk of Adverse Outcomes in Patients After an Acute
      Coronary Syndrome: Observations From the SOLID-TIMI 52 (Stabilization of Plaque
      Using Darapladib-Thrombolysis in Myocardial Infarction 52) Trial.
AB  - BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque
      instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic
      implications of IL-6 post-ACS. METHODS AND RESULTS: IL-6 concentration was
      assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque
      Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of
      darapladib in patients <=30 days from ACS. Patients were followed for a median of
      2.5 years for major adverse cardiovascular events; cardiovascular death,
      myocardial infarction, or stroke) and cardiovascular death or heart failure
      hospitalization. Primary analyses were adjusted first for baseline
      characteristics, days from index ACS, ACS type, and randomized treatment arm. For
      every SD increase in IL-6, there was a 10% higher risk of major adverse
      cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence
      interval [CI] 1.01-1.19) and a 22% higher risk of cardiovascular death or heart
      failure (adj HR 1.22, 95% CI 1.11-1.34). Patients in the highest IL-6 quartile
      had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95%
      CI 1.22-2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6
      3.29). After further adjustment for biomarkers (high-sensitivity C-reactive
      protein, lipoprotein-associated phospholipase A2 activity, high-sensitivity
      troponin I, and B-type natriuretic peptide), IL-6 remained significantly
      associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1
      1.43, 95% CI 1.09-1.88) and cardiovascular death or heart failure (adj HR 1.79,
      95% CI 1.22-2.63). CONCLUSIONS: In patients after ACS, IL-6 concentration is
      associated with adverse cardiovascular outcomes independent of established risk
      predictors and biomarkers. These findings lend support to the concept of IL-6 as
      a potential therapeutic target in patients with unstable ischemic heart disease.

PMID- 29066437
TI  - Effects of Vitamin D on Blood Pressure, Arterial Stiffness, and Cardiac Function
      in Older People After 1 Year: BEST-D (Biochemical Efficacy and Safety Trial of
      Vitamin D).
AB  - BACKGROUND: The relevance of vitamin D for prevention of cardiovascular disease
      is uncertain. The BEST-D (Biochemical Efficacy and Safety Trial of vitamin D)
      trial previously reported effects of vitamin D on plasma markers of vitamin D
      status, and the present report describes the effects on blood pressure, heart
      rate, arterial stiffness, and cardiac function. METHODS AND RESULTS: This was a
      randomized, double-blind, placebo-controlled trial of 305 older people living in
      United Kingdom, who were allocated vitamin D 4000 IU (100 MUg), vitamin D 2000 IU
      (50 MUg), or placebo daily. Primary outcomes were plasma concentrations of 25
      hydroxy-vitamin D and secondary outcomes were blood pressure, heart rate, and
      arterial stiffness in all participants at 6 and 12 months, plasma N-terminal
      prohormone of brain natriuretic peptide levels in all participants at 12 months,
      and echocardiographic measures of cardiac function in a randomly selected subset
      (n=177) at 12 months. Mean (SE) plasma 25-hydroxy-vitamin D concentrations were
      50 (SE 2) nmol/L at baseline and increased to 137 (2.4), 102 (2.4), and 53 (2.4)
      nmol/L after 12 months in those allocated 4000 IU/d, 2000 IU/d of vitamin D, or
      placebo, respectively. Allocation to vitamin D had no significant effect on mean
      levels of blood pressure, heart rate, or arterial stiffness at either 6 or 12
      months, nor on any echocardiographic measures of cardiac function, or plasma N
      terminal prohormone of brain natriuretic peptide concentration at 12 months.
      CONCLUSIONS: The absence of any significant effect of vitamin D on blood
      pressure, arterial stiffness, or cardiac function suggests that any beneficial
      effects of vitamin D on cardiovascular disease are unlikely to be mediated
      through these mechanisms. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrialsregister.eu/ctr-search/search. Unique identifier:
      EudraCT number: 2011-005763-24a.

PMID- 29066439
TI  - Pulmonary Hypertension and Pregnancy Outcomes: Insights From the National
      Inpatient Sample.
AB  - BACKGROUND: Pregnant women with pulmonary hypertension (PH) are at risk for
      adverse cardiac outcomes, particularly at the time of labor and delivery. The
      purpose of this study is to define the impact of PH on pregnancy outcomes and the
      risk of major adverse cardiac events (MACE). METHODS AND RESULTS: The National
      Inpatient Sample was screened for hospital admissions of women delivering during
      the years 2003 to 2012. The primary outcome was MACE, a composite of death,
      cardiac arrest, cardiogenic shock, myocardial infarction, respiratory failure,
      arrhythmia, stroke, and embolic event. Data on 1519 patients with PH and 6 757
      582 without heart disease or PH were available. There were 59.6% with isolated
      PH; 10.7% with PH and congenital heart disease; 18.1% with PH and valvular heart
      disease; 3% with PH and valvular heart disease and congenital heart disease; 6.6%
      PH and cardiomyopathy; and 1.9% with PH and cardiomyopathy and valvular heart
      disease. Compared with women without heart disease or PH, women with PH
      experienced significantly higher MACE (24.8 versus 0.4%, P<0.0001). Among the
      subsets of women with PH, the highest MACE was noted in women with the
      combination of PH and cardiomyopathy and valvular heart disease, and PH and
      cardiomyopathy, primarily because of heart failure and arrhythmia. Women with PH
      were significantly more likely to experience eclampsia syndromes, preterm
      delivery, and intrauterine fetal demise (P<0.0001 for all). PH subtype was
      significantly associated with MACE in multivariable analysis (P<0.001).
      CONCLUSIONS: In a contemporary data set of pregnant women in the United States,
      PH was associated with an increase in MACE during the hospitalization for
      delivery, with an exceptionally elevated risk among women with associated
      cardiomyopathy.

PMID- 29066438
TI  - Polo-Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early
      Lineage Specification Downstream of Yes-Associated Protein 1 in Cardiac
      Progenitor Cells.
AB  - BACKGROUND: Recent studies suggest that adult cardiac progenitor cells (CPCs) can
      produce new cardiac cells. Such cell formation requires an intricate coordination
      of progenitor cell proliferation and commitment, but the molecular cues
      responsible for this regulation in CPCs are ill defined. METHODS AND RESULTS:
      Extracellular matrix components are important instructors of cell fate. Using
      laminin and fibronectin, we induced two slightly distinct CPC phenotypes
      differing in proliferation rate and commitment status and analyzed the early
      transcriptomic response to CPC adhesion (<2 hours). Ninety-four genes were
      differentially regulated on laminin versus fibronectin, consisting of mostly
      downregulated genes that were enriched for Yes-associated protein (YAP) conserved
      signature and TEA domain family member 1 (TEAD1)-related genes. This early gene
      regulation was preceded by the rapid cytosolic sequestration and degradation of
      YAP on laminin. Among the most strongly regulated genes was polo-like kinase 2
      (Plk2). Plk2 expression depended on YAP stability and was enhanced in CPCs
      transfected with a nuclear-targeted mutant YAP. Phenotypically, the early
      downregulation of Plk2 on laminin was succeeded by lower cell proliferation,
      enhanced lineage gene expression (24 hours), and facilitated differentiation (3
      weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC
      proliferation and knockdown of Plk2 induced the expression of lineage genes.
      CONCLUSIONS: Plk2 acts as coordinator of cell proliferation and early lineage
      commitment in CPCs. The rapid downregulation of Plk2 on YAP inactivation marks a
      switch towards enhanced commitment and facilitated differentiation. These
      findings link early gene regulation to cell fate and provide novel insights into
      how CPC proliferation and differentiation are orchestrated.

PMID- 29066440
TI  - Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of
      Patients With Obesity-Driven Heart Failure With a Preserved Ejection Fraction.
AB  - BACKGROUND: Respiratory muscle weakness contributes to exercise intolerance in
      patients with heart failure with a preserved ejection fraction (HFpEF)-a
      condition characterized by multiple comorbidities with few proven treatments. We
      aimed, therefore, to provide novel insight into the underlying diaphragmatic
      alterations that occur in HFpEF by using an obese cardiometabolic rat model and
      further assessed whether exercise training performed only after the development
      of overt HFpEF could reverse impairments. METHODS AND RESULTS: Obese ZSF1 rats
      (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3
      additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of
      either sedentary behavior (n=13), high-intensity interval training (n=11), or
      moderate-continuous training (n=11). Obese rats developed an obvious HFpEF
      phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift
      towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower
      protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile
      functional impairments were observed. At 28 weeks, neither the exercise training
      regimen of high-intensity interval training or moderate-continuous training
      reversed any of the diaphragm alterations induced by HFpEF. CONCLUSIONS: This
      study, using a well-characterized rat model of HFpEF underpinned by multiple
      comorbidities and exercise intolerance (ie, one that closely resembles the
      patient phenotype), provides evidence that diaphragm alterations and dysfunction
      induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise
      training. As such, whether alternative therapeutic interventions are required to
      treat respiratory muscle weakness in HFpEF warrants further investigation.

PMID- 29066441
TI  - Endoplasmic Reticulum Stress Is Associated With Autophagy and Cardiomyocyte
      Remodeling in Experimental and Human Atrial Fibrillation.
AB  - BACKGROUND: Derailment of proteostasis, the homeostasis of production, function,
      and breakdown of proteins, contributes importantly to the self-perpetuating
      nature of atrial fibrillation (AF), the most common heart rhythm disorder in
      humans. Autophagy plays an important role in proteostasis by degrading aberrant
      proteins and organelles. Herein, we investigated the role of autophagy and its
      activation pathway in experimental and clinical AF. METHODS AND RESULTS:
      Tachypacing of HL-1 atrial cardiomyocytes causes a gradual and significant
      activation of autophagy, as evidenced by enhanced LC3B-II expression, autophagic
      flux and autophagosome formation, and degradation of p62, resulting in reduction
      of Ca2+ amplitude. Autophagy is activated downstream of endoplasmic reticulum
      (ER) stress: blocking ER stress by the chemical chaperone 4-phenyl butyrate,
      overexpression of the ER chaperone-protein heat shock protein A5, or
      overexpression of a phosphorylation-blocked mutant of eukaryotic initiation
      factor 2alpha (eIF2alpha) prevents autophagy activation and Ca2+-transient loss
      in tachypaced HL-1 cardiomyocytes. Moreover, pharmacological inhibition of ER
      stress in tachypaced Drosophila confirms its role in derailing cardiomyocyte
      function. In vivo treatment with sodium salt of phenyl butyrate protected atrial
      tachypaced dog cardiomyocytes from electrical remodeling (action potential
      duration shortening, L-type Ca2+-current reduction), cellular Ca2+
      handling/contractile dysfunction, and ER stress and autophagy; it also attenuated
      AF progression. Finally, atrial tissue from patients with persistent AF reveals
      activation of autophagy and induction of ER stress, which correlates with markers
      of cardiomyocyte damage. CONCLUSIONS: These results identify ER stress-associated
      autophagy as an important pathway in AF progression and demonstrate the potential
      therapeutic action of the ER-stress inhibitor 4-phenyl butyrate.

PMID- 29066442
TI  - Cruciferous and Allium Vegetable Intakes are Inversely Associated With 15-Year
      Atherosclerotic Vascular Disease Deaths in Older Adult Women.
AB  - BACKGROUND: Higher vegetable intake is consistently associated with lower
      atherosclerotic vascular disease (ASVD) events. However, the components
      responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals
      may be involved. The objective of this study was to investigate the associations
      of total vegetable intake and types of vegetables grouped according to
      phytochemical constituents with ASVD mortality. METHODS AND RESULTS: The cohort
      consisted of 1226 Australian women aged 70 years and older without clinical ASVD
      or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per
      serving (75 g/d) and were also classified into prespecified types relating to
      phytochemical constituents. ASVD-related deaths were ascertained from linked
      mortality data. During 15 years (15 947 person-years) of follow-up, 238 ASVD
      related deaths occurred. A 1-serving increment of vegetable intake was associated
      with a 20% lower hazard of ASVD-related death (multivariable-adjusted hazard
      ratio, 0.80; 95% confidence interval, 0.69-0.94 [P=0.005]). In multivariable
      adjusted models for vegetable types, cruciferous (per 10-g/d increase: hazard
      ratio, 0.87; 95% confidence interval, 0.81-0.94 [P<0.001]) and allium (per 5-g/d
      increase: hazard ratio, 0.82; 95% confidence interval, 0.73-0.94 [P=0.003])
      vegetables were inversely associated with ASVD-related deaths. The inclusion of
      other vegetable types, as well as lifestyle and cardiovascular risk factors, did
      not alter these associations. Yellow/orange/red (P=0.463), leafy green (P=0.063),
      and legume (P=0.379) vegetables were not significant. CONCLUSIONS: Consistent
      with current evidence, higher cruciferous and allium vegetable intakes were
      associated with a lower risk of ASVD mortality. In addition, cruciferous and
      allium vegetables are recognized to be a good source of several nonnutritive
      phytochemicals such as organosulfur compounds. CLINICAL TRIAL REGISTRATION: URL:
      http://www.anzctr.org.au. Unique identifier: ACTRN12617000640303.

PMID- 29066443
TI  - Advanced Age and Post-Acute Care Outcomes After Subarachnoid Hemorrhage.
AB  - BACKGROUND: Older patients with aneurysmal subarachnoid hemorrhage (aSAH) are
      unique, and determinants of post-acute care outcomes are not well elucidated. The
      primary objective was to identify hospital characteristics associated with 30-day
      readmission and mortality rates after hospital discharge among older patients
      with aSAH. METHODS AND RESULTS: This cohort study used Medicare patients >=65
      years discharged from US hospitals from January 1, 2008, to November 30, 2010,
      after aSAH. Medicare data were linked to American Hospital Association data to
      describe characteristics of hospitals treating these patients. Using
      multivariable logistic regression to adjust for patient characteristics, hospital
      factors associated with (1) hospital readmission and (2) mortality within 30 days
      after discharge were identified. A total of 5515 patients >=65 years underwent
      surgical repair for aSAH in 431 hospitals. Readmission rate was 17%, and 8.5% of
      patients died within 30 days of discharge. In multivariable analyses, patients
      treated in hospitals with lower annualized aSAH volumes were more likely to be
      readmitted 30 days after discharge (lowest versus highest quintile, 1-2 versus 16
      30 cases; adjusted odds ratio, 2.10; 95% confidence interval, 1.56-2.84).
      Patients treated in hospitals with lower annualized aSAH volumes (lowest versus
      highest quintile: adjusted odds ratio, 1.52; 95% confidence interval, 1.05-2.19)
      had a greater likelihood of dying 30 days after discharge. CONCLUSIONS: Older
      patients with aSAH discharged from hospitals treating lower volumes of such cases
      are at greater risk of readmission and dying within 30 days. These findings may
      guide clinician referrals, practice guidelines, and regulatory policies
      influencing which hospitals should care for older patients with aSAH.

PMID- 29066444
TI  - Effect of Monthly, High-Dose, Long-Term Vitamin D Supplementation on Central
      Blood Pressure Parameters: A Randomized Controlled Trial Substudy.
AB  - BACKGROUND: The effects of monthly, high-dose, long-term (>=1-year) vitamin D
      supplementation on central blood pressure (BP) parameters are unknown. METHODS
      AND RESULTS: A total of 517 adults (58% male, aged 50-84 years) were recruited
      into a double-blinded, placebo-controlled trial substudy and randomized to
      receive, for 1.1 years (median; range: 0.9-1.5 years), either (1) vitamin D3 200
      000 IU (initial dose) followed 1 month later by monthly 100 000-IU doses (n=256)
      or (2) placebo monthly (n=261). At baseline (n=517) and follow-up (n=380),
      suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and
      hemodynamic parameters. Mean deseasonalized 25-hydroxyvitamin D increased from 66
      nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow-up in the vitamin D
      group, with no change in the placebo group. Despite small, nonsignificant changes
      in hemodynamic parameters in the total sample (primary outcome), we observed
      consistently favorable changes among the 150 participants with vitamin D
      deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the
      vitamin D group (n=71) versus placebo group (n=79) were -5.3 mm Hg (95%
      confidence interval [CI], -11.8 to 1.3) for brachial systolic BP (P=0.11), -2.8
      mm Hg (95% CI, -6.2 to 0.7) for brachial diastolic BP (P=0.12), -7.5 mm Hg (95%
      CI, -14.4 to -0.6) for aortic systolic BP (P=0.03), -5.7 mm Hg (95% CI, -10.8 to 
      0.6) for augmentation index (P=0.03), -0.3 m/s (95% CI, -0.6 to -0.1) for pulse
      wave velocity (P=0.02), -8.6 mm Hg (95% CI, -15.4 to -1.9) for peak reservoir
      pressure (P=0.01), and -3.6 mm Hg (95% CI, -6.3 to -0.8) for backward pressure
      amplitude (P=0.01). CONCLUSIONS: Monthly, high-dose, 1-year vitamin D
      supplementation lowered central BP parameters among adults with vitamin D
      deficiency but not in the total sample. CLINICAL TRIAL REGISTRATION: URL:
      http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943.

PMID- 29066445
TI  - Collecting Duct Nitric Oxide Synthase 1beta Activation Maintains Sodium
      Homeostasis During High Sodium Intake Through Suppression of Aldosterone and
      Renal Angiotensin II Pathways.
AB  - BACKGROUND: During high sodium intake, the renin-angiotensin-aldosterone system
      is downregulated and nitric oxide signaling is upregulated in order to remain in
      sodium balance. Recently, we showed that collecting duct nitric oxide synthase
      1beta is critical for fluid-electrolyte balance and subsequently blood pressure
      regulation during high sodium feeding. The current study tested the hypothesis
      that high sodium activation of the collecting duct nitric oxide synthase 1beta
      pathway is critical for maintaining sodium homeostasis and for the downregulation
      of the renin-angiotensin-aldosterone system-epithelial sodium channel axis.
      METHODS AND RESULTS: Male control and collecting duct nitric oxide synthase 1beta
      knockout (CDNOS1KO) mice were placed on low, normal, and high sodium diets for 1
      week. In response to the high sodium diet, plasma sodium was significantly
      increased in control mice and to a significantly greater level in CDNOS1KO mice.
      CDNOS1KO mice did not suppress plasma aldosterone in response to the high sodium
      diet, which may be partially explained by increased adrenal AT1R expression.
      Plasma renin concentration was appropriately suppressed in both genotypes.
      Furthermore, CDNOS1KO mice had significantly higher intrarenal angiotensin II
      with high sodium diet, although intrarenal angiotensinogen levels and angiotensin
      converting enzyme activity were similar between knockout mice and controls. In
      agreement with inappropriate renin-angiotensin-aldosterone system activation in
      the CDNOS1KO mice on a high sodium diet, epithelial sodium channel activity and
      sodium transporter abundance were significantly higher compared with controls.
      CONCLUSIONS: These data demonstrate that high sodium activation of collecting
      duct nitric oxide synthase 1beta signaling induces suppression of systemic and
      intrarenal renin-angiotensin-aldosterone system, thereby modulating epithelial
      sodium channel and other sodium transporter abundance and activity to maintain
      sodium homeostasis.

PMID- 29066446
TI  - Benefit of Vasodilating beta-Blockers in Patients With Acute Myocardial
      Infarction After Percutaneous Coronary Intervention: Nationwide Multicenter
      Cohort Study.
AB  - BACKGROUND: Although current guidelines recommend beta-blocker after acute
      myocardial infarction (MI), the role of beta-blocker has not been well
      investigated in the modern reperfusion era. In particular, the benefit of
      vasodilating beta-blocker over conventional beta-blocker is still unexplored.
      METHODS AND RESULTS: Using nation-wide multicenter Korean Acute Myocardial
      Infarction Registry data, we analyzed clinical outcomes of 7127 patients with
      acute MI who underwent successful percutaneous coronary intervention with stents
      and took beta-blockers: vasodilating beta-blocker (n=3482), and conventional beta
      blocker (n=3645). In the whole population, incidence of cardiac death at 1 year
      was significantly lower in the vasodilating beta-blocker group (vasodilating beta
      blockers versus conventional beta-blockers, 1.0% versus 1.9%; P=0.003). In 2882
      pairs of propensity score-matched population, the incidence of cardiac death was
      significantly lower in the vasodilating beta-blocker group (1.1% versus 1.8%;
      P=0.028). Although incidences of MI (1.1% versus 1.5%; P=0.277), any
      revascularization (2.8% versus 3.0%; P=0.791), and hospitalization for heart
      failure (1.4% versus 1.9%; P=0.210) were not different between the 2 groups,
      incidences of cardiac death or MI (2.0% versus 3.1%; P=0.010), cardiac death, MI,
      or hospitalization for heart failure (3.0% versus 4.5%; P=0.003), cardiac death,
      MI, or any revascularization (3.9% versus 5.3%; P=0.026), and cardiac death, MI,
      any revascularization, or hospitalization for heart failure (4.8% versus 6.5%;
      P=0.011) were significantly lower in the vasodilating beta-blocker group.
      CONCLUSIONS: Vasodilating beta-blocker therapy resulted in better clinical
      outcomes than conventional beta-blocker therapy did in patients with acute MI in
      the modern reperfusion era. Vasodilating beta-blockers could be recommended
      preferentially to conventional ones for acute MI patients.

PMID- 29066447
TI  - Impact of Sustained Use of a Multifaceted Computerized Quality Improvement
      Intervention for Cardiovascular Disease Management in Australian Primary Health
      Care.
AB  - BACKGROUND: We evaluated a multifaceted, computerized quality improvement
      intervention for management of cardiovascular disease (CVD) risk in Australian
      primary health care. After completion of a cluster randomized controlled trial,
      the intervention was made available to both trial arms. Our objective was to
      assess intervention outcomes in the post-trial period and any heterogeneity based
      on original intervention allocation. METHODS AND RESULTS: Data from 41 health
      services were analyzed. Outcomes were (1) proportion of eligible population with
      guideline-recommended CVD risk factor measurements; and (2) the proportion at
      high CVD risk with current prescriptions for guideline-recommended medications.
      Patient-level analyses were conducted using generalized estimating equations to
      account for clustering and time effects and tests for heterogeneity were
      conducted to assess impact of original treatment allocation. Median follow-up for
      22 809 patients (mean age, 64.2 years; 42.5% men, 26.5% high CVD risk) was 17.9
      months post-trial and 35 months since trial inception. At the end of the post
      trial period there was no change in CVD risk factor screening overall when
      compared with the end of the trial period (64.7% versus 63.5%, P=0.17). For
      patients at high CVD risk, there were significant improvements in recommended
      prescriptions at end of the post-trial period when compared with the end of the
      trial period (65.2% versus 56.0%, P<0.001). There was no heterogeneity of
      treatment effects on the outcomes based on original randomization allocation.
      CONCLUSIONS: CVD risk screening improvements were not observed in the post-trial
      period. Conversely, improvements in prescribing continued, suggesting that
      changes in provider and patient actions may take time when initiating
      medications. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique
      identifier: 12611000478910.

PMID- 29066449
TI  - Effect of Vitamin D Supplementation on Arterial Stiffness and Central Blood
      Pressure Indexes: Demystifying the Evidence.

PMID- 29066448
TI  - Impact of Regional Systems of Care on Disparities in Care Among Female and Black
      Patients Presenting With ST-Segment-Elevation Myocardial Infarction.
AB  - BACKGROUND: The American Heart Association Mission: Lifeline STEMI (ST-segment
      elevation myocardial infarction) Systems Accelerator program, conducted in 16
      regions across the United States to improve key care processes, resulted in more
      patients being treated within national guideline goals (time from first medical
      contact to device: <90 minutes for direct presenters to hospitals capable of
      performing percutaneous coronary intervention; <120 minutes for transfers). We
      examined whether the effort reduced reperfusion disparities in the proportions of
      female versus male and black versus white patients. METHODS AND RESULTS: In
      total, 23 809 patients (29.3% female, 82.3% white, and 10.7% black) presented
      with acute STEMI between July 2012 and March 2014. Change in the proportion of
      patients treated within guideline goals was compared between sex and race
      subgroups for patients presenting directly to hospitals capable of performing
      percutaneous coronary intervention (n=18 267) and patients requiring transfer
      (n=5542). The intervention was associated with an increase in the proportion of
      men treated within guideline goals that presented directly (58.7-62.1%, P=0.01)
      or were transferred (43.3-50.7%, P<0.01). An increase was also seen among white
      patients who presented directly (57.7-59.9%, P=0.02) or were transferred (43.9
      48.8%, P<0.01). There was no change in the proportion of female or black patients
      treated within guideline goals, including both those presenting directly and
      transferred. CONCLUSION: The STEMI Systems Accelerator project was associated
      with an increase in the proportion of patients meeting guideline reperfusion
      targets for male and white patients but not for female or black patients. Efforts
      to organize systems of STEMI care should implement additional processes targeting
      barriers to timely reperfusion among female and black patients.

PMID- 29066450
TI  - Pretenders and Contenders: Inflammation, C-Reactive Protein, and Interleukin-6.

PMID- 29066451
TI  - Cardiovascular Disease in American Indian and Alaska Native Youth: Unique Risk
      Factors and Areas of Scholarly Need.

PMID- 29066454
TI  - The Imperative Authentication of Cell Lines.

PMID- 29066453
TI  - Cumulative Exposure to High-Sensitivity C-Reactive Protein Predicts the Risk of
      Cardiovascular Disease.
AB  - BACKGROUND: One measurement of hs-CRP (high-sensitivity C-reactive protein) is
      associated with increased risk of cardiovascular disease (CVD). The objective of
      this study was to characterize the association of cumulative exposure to
      increased hs-CRP with incident cardiovascular events. METHODS AND RESULTS: We
      included 53 065 participants with hs-CRP measured at 3 examinations in 2006,
      2008, and 2010. Cumulative exposure to hs-CRP was calculated as the weighted sum
      of the average hs-CRP level for each time interval (level*time). Participants
      were classified into nonexposed group (hs-CRP<3.0 mg/L in all 3 examinations), 1
      exposed group (hs-CRP>=3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs
      CRP>=3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP>=3.0 mg/L
      in 3 examinations). Cox proportional hazards models were used to assess the
      association of cumulative hs-CRP with incident CVD. The study showed a dose
      response pattern with risk of CVD and myocardial infarction as the number of
      years of exposure to hs-CRP increases. Participants in the 3-exposed group had
      significantly increased CVD risk with hazard ratio (95% confidence interval) of
      1.38 (1.11-1.72), in comparison with 1.28 (1.07-1.52) for participants in the 2
      exposed group and 1.13 (0.97-1.31) for those in the 1-exposed group (P<0.05);
      meanwhile, the similar and significant associations were also observed for
      myocardial infarction with respective hazard ratio (95% confidence interval) of
      2.13 (1.42-3.18), 1.60 (1.12-2.27), and 1.57 (1.17-2.10). The associations
      between stroke and cumulative hs-CRP were not statistically significant
      (P=0.360). CONCLUSIONS: Cumulative exposure to hs-CRP was dose dependently
      associated with a subsequent increased risk of CVD and myocardial infarction.
      CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique
      identifier: ChiCTR-TNC-11001489.

PMID- 29066452
TI  - Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in
      Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of
      Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial.
AB  - BACKGROUND: Evaluation of cardiovascular prognosis in patients with stable
      coronary heart disease is based on clinical characteristics and biomarkers
      indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac
      dysfunction. Inflammation plays a key role in atherosclerosis, but the
      association between inflammatory biomarkers and clinical outcomes is less studied
      in this population. METHODS AND RESULTS: Overall, 15 828 patients with coronary
      heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by
      Initiation of Darapladib Therapy) trial were randomized to treatment with
      darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients,
      levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein were
      measured in plasma samples: median levels were 2.1 (interquartile range, 1.4-3.2)
      ng/L and 1.3 (interquartile range, 0.6-3.1) mg/L, respectively. Associations
      between continuous levels or quartile groups and adjudicated outcomes were
      evaluated by spline graphs and Cox regression adjusted for clinical factors and
      cardiovascular biomarkers. IL-6 was associated with increased risk of major
      adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR],
      1.60; 95% confidence interval [CI], 1.30-1.97; P<0.0001); cardiovascular death
      (HR, 2.15; 95% CI, 1.53-3.04; P<0.0001); myocardial infarction (HR, 1.53; 95% CI,
      1.14-2.04; P<0.05); all-cause mortality (HR, 2.11; 95% CI, 1.62-2.76; P<0.0001);
      and risk of hospitalization for heart failure (HR, 2.28; 95% CI, 1.34-3.89;
      P<0.001). Cancer death was doubled in the highest IL-6 quartile group (HR, 2.34;
      95% CI, 1.20-4.53; P<0.05). High-sensitivity C-reactive protein was associated
      with both cardiovascular and non-cardiovascular events in the unadjusted model,
      but these did not remain after multivariable adjustments. CONCLUSIONS: IL-6, an
      upstream inflammatory marker, was independently associated with the risk of major
      adverse cardiovascular events, cardiovascular and all-cause mortality, myocardial
      infarction, heart failure, and cancer mortality in patients with stable coronary
      heart disease. IL-6 might reflect a pathophysiological process involved in the
      development of these events. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00799903.

PMID- 29066455
TI  - Reply to Rojas, "The Imperative Authentication of Cell Lines".

PMID- 29066456
TI  - Erratum for Martinez-Florensa et al., "Protective Effects of Human and Mouse
      Soluble Scavenger-Like CD6 Lymphocyte Receptor in a Lethal Model of Polymicrobial
      Sepsis".

PMID- 29066458
TI  - Street art for promoting health in communities in the West.

PMID- 29066457
TI  - A helping hand to relative safety.

PMID- 29066460
TI  - Improving attitudes to hearing loss.

PMID- 29066459
TI  - Branched-chain ketoacids secreted by glioblastoma cells via MCT1 modulate
      macrophage phenotype.
AB  - Elevated amino acid catabolism is common to many cancers. Here, we show that
      glioblastoma are excreting large amounts of branched-chain ketoacids (BCKAs),
      metabolites of branched-chain amino acid (BCAA) catabolism. We show that efflux
      of BCKAs, as well as pyruvate, is mediated by the monocarboxylate transporter 1
      (MCT1) in glioblastoma. MCT1 locates in close proximity to BCKA-generating
      branched-chain amino acid transaminase 1, suggesting possible functional
      interaction of the proteins. Using in vitro models, we demonstrate that tumor
      excreted BCKAs can be taken up and re-aminated to BCAAs by tumor-associated
      macrophages. Furthermore, exposure to BCKAs reduced the phagocytic activity of
      macrophages. This study provides further evidence for the eminent role of BCAA
      catabolism in glioblastoma by demonstrating that tumor-excreted BCKAs might have
      a direct role in tumor immune suppression. Our data further suggest that the anti
      proliferative effects of MCT1 knockdown observed by others might be related to
      the blocked excretion of BCKAs.

PMID- 29066461
TI  - Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet
      by improving energy expenditure and insulin sensitivity.
AB  - The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the
      activity of the electroneutral cation-chloride cotransporters (SLC12 family) and
      thus physiological processes such as modulation of cell volume, intracellular
      chloride concentration [Cl-]i, and transepithelial salt transport. Modulation of
      SPAK kinase activity may have an impact on hypertension and obesity, as STK39,
      the gene encoding SPAK, has been suggested as a hypertension and obesity
      susceptibility gene. In fact, the absence of SPAK activity in mice in which the
      activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is
      associated with decreased blood pressure; however its consequences in metabolism
      have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high
      fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones,
      energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice
      exhibit resistance to HFD-induced obesity and hepatic steatosis associated with
      increased energy expenditure, higher thermogenic activity in brown adipose
      tissue, increased mitochondrial activity in skeletal muscle, and reduced white
      adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity
      and glucose tolerance. Our data reveal a previously unrecognized role for the
      SPAK kinase in the regulation of energy balance, thermogenesis, and insulin
      sensitivity, suggesting that this kinase could be a new drug target for the
      treatment of obesity and the metabolic syndrome.

PMID- 29066462
TI  - Genetic ablation of Cyp8b1 preserves host metabolic function by repressing
      steatohepatitis and altering gut microbiota composition.
AB  - Both type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH) are associated
      with reduced hepatic mitochondrial respiratory capacity. Cholic acid (CA) is the
      predominant 12alpha-hydroxylated bile acid that regulates hepatic lipid
      metabolism, and its circulating levels are negatively correlated with insulin
      resistance. Abolishing CA synthesis via the genetic disruption of the enzyme
      sterol 12alpha-hydroxylase ( Cyp8b1-/-) leads in resistance to diabetes and
      hepatic steatosis. Here, we show that long-term stimulation of hepatic
      lipogenesis leads to a severe impairment in overall metabolic and respiratory
      function in control mice ( Cyp8b1+/+) but strikingly not in Cyp8b1-/- mice.
      Cyp8b1-/- mice are protected from such metabolic impairments associated with T2D
      and NASH by inhibiting hepatic de novo lipogenic gene and protein expression and
      altering gut microbiota composition. The protective phenotype is compromised when
      NASH induction is independent of impairment in de novo lipogenesis (DNL).
      Consequently, Cyp8b1-/- mice also show a reduction in hepatic inflammation and
      fibrosis along with a shift in antimicrobial dynamics in the small intestine. Our
      data show that the altered bile acid composition of Cyp8b1-/- mice preserves
      metabolic and respiratory function by repressing hepatic DNL and driving
      favorable changes in gut antimicrobial responses.

PMID- 29066463
TI  - Angiotensin 1-7 stimulates brown adipose tissue and reduces diet-induced obesity.
AB  - The renin-angiotensin system is a key regulator of metabolism with beneficial
      effects of the angiotensin 1-7 (Ang 1-7) peptide. We hypothesized that the
      antiobesity effect of Ang 1-7 was related to the stimulation of brown adipose
      tissue (BAT). We administered Ang 1-7 (0.54 mg kg-1 day-1) for 28 days via
      implanted micro-osmotic pumps to mice with high-fat diet (HFD)-induced obesity.
      Ang 1-7 treatment reduced body weight, upregulated thermogenesis, and ameliorated
      impaired glucose homeostasis without affecting food consumption. Furthermore, Ang
      1-7 treatment enlarged BAT and the increased expression of UCP1, PRDM16, and
      prohibitin. Alterations in PRDM16 expression correlated with increased AMPK and
      phosphorylation of mTOR. Ang 1-7 treatment elevated thermogenesis in subcutaneous
      white adipose tissue without altering UCP1 expression. These changes occurred in
      the context of decreased lipid accumulation in BAT from HFD-fed mice, preserved
      insulin signaling concomitant with phosphorylation of hormone-sensitive lipase
      and decreased expression of perilipin. These data suggest that Ang 1-7 induces
      brown adipocyte differentiation leading to upregulation of thermogenesis and
      improved metabolic profile in diet-induced obesity. Enhancing Ang 1-7 action
      represents a promising therapy to increase BAT and to reduce the metabolic
      complications associated with diet-induced obesity.

PMID- 29066465
TI  - Vikas Saini: a career protecting patients from the excesses of medicine.

PMID- 29066464
TI  - Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results
      from the open-label period of a phase II randomised controlled trial
      (faSScinate).
AB  - OBJECTIVES: Assess the efficacy and safety of tocilizumab in patients with
      systemic sclerosis (SSc) in a phase II study. METHODS: Patients with SSc were
      treated for 48 weeks in an open-label extension phase of the faSScinate study
      with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included
      modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity
      (%pFVC) through week 96. RESULTS: Overall, 24/44 (55%) placebo-tocilizumab and
      27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD
      (95% CI)) change from baseline in mRSS was -3.1 (6.3 (-5.4 to -0.9)) for placebo
      and -5.6 (9.1 (-8.9 to-2.4)) for tocilizumab at week 48 and -9.4 (5.6 (-8.9 to 
      2.4)) for placebo-tocilizumab and -9.1 (8.7 (-12.5 to -5.6)) for continuous
      tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC
      was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26
      (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label
      period; no patients had >10% absolute decline in %pFVC. Serious infection
      rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8
      (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and
      19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous
      tocilizumab during the open-label period. CONCLUSIONS: Skin score improvement and
      FVC stabilisation in the double-blind period were observed in placebo-treated
      patients who transitioned to tocilizumab and were maintained in the open-label
      period. Safety data indicated increased serious infections in patients with SSc
      but no new safety signals with tocilizumab. TRIAL REGISTRATION NUMBER:
      NCT01532869; Results.

PMID- 29066467
TI  - Getting an "A": Report Cards for Reducing Health Care Waste.

PMID- 29066466
TI  - DGKzeta deficiency protects against peripheral insulin resistance and improves
      energy metabolism.
AB  - Diacylglycerol kinases (DGKs) regulate the balance between diacylglycerol (DAG)
      and phosphatidic acid. DGKzeta is highly abundant in skeletal muscle and induces
      fiber hypertrophy. We hypothesized that DGKzeta influences functional and
      metabolic adaptations in skeletal muscle and whole-body fuel utilization. DAG
      content was increased in skeletal muscle and adipose tissue, but unaltered in
      liver of DGKzeta KO mice. Linear growth, body weight, fat mass, and lean mass
      were reduced in DGKzeta KO versus wild-type mice. Conversely, male DGKzeta KO and
      wild-type mice displayed a similar robust increase in plantaris weight after
      functional overload, suggesting that DGKzeta is dispensable for muscle
      hypertrophy. Although glucose tolerance was similar, insulin levels were reduced
      in high-fat diet (HFD)-fed DGKzeta KO versus wild-type mice. Submaximal insulin
      stimulated glucose transport and p-Akt Ser473 were increased, suggesting enhanced
      skeletal muscle insulin sensitivity. Energy homeostasis was altered in DGKzeta KO
      mice, as evidenced by an elevated respiratory exchange ratio, independent of
      altered physical activity or food intake. In conclusion, DGKzeta deficiency
      increases tissue DAG content and leads to modest growth retardation, reduced
      adiposity, and protection against insulin resistance. DGKzeta plays a role in the
      control of growth and metabolic processes, further highlighting specialized
      functions of DGK isoforms in type 2 diabetes pathophysiology.

PMID- 29066468
TI  - Choosing Wisely Campaign: Report Card and Achievable Benchmarks of Care for
      Children's Hospitals.
AB  - OBJECTIVES: In 2013, the Society of Hospital Medicine (SHM) released 5 pediatric
      recommendations for the Choosing Wisely Campaign (CWC). Our goals were to develop
      a report card on the basis of those recommendations, calculate achievable
      benchmarks of care (ABCs), and analyze performance among hospitals participating
      in the Pediatric Health Information System. METHODS: Children hospitalized
      between January 2013 and September 2015 from 32 Pediatric Health Information
      System hospitals were studied. The quality metrics in the report card included
      the use of chest radiograph (CXR) in asthma and bronchiolitis, bronchodilators in
      bronchiolitis, systemic corticosteroids in lower respiratory tract infections
      (LRTI), and acid suppression therapy in gastroesophageal reflux (GER). ABCs were
      calculated for each metric. RESULTS: Calculated ABCs were 22.3% of patients with
      asthma and 19.8% of patients with bronchiolitis having a CXR, 17.9% of patients
      with bronchiolitis receiving bronchodilators, 5.5% of patients with LRTIs treated
      with systemic corticosteroids, and 32.2% of patients with GER treated with acid
      suppressors. We found variation among hospitals in the use of CXR in asthma
      (median: 34.7%, interquartile range [IQR]: 28.5%-45.9%), CXR in bronchiolitis
      (median: 34.4%, IQR: 27.9%-49%), bronchodilators in bronchiolitis (median: 55.4%,
      IQR: 32.3%-64.9%), and acid suppressors in GER (median: 59.4%, IQR: 49.9%-71.2%).
      Less variation was noted in the use of systemic corticosteroids in LRTIs (median:
      13.5%, IQR: 11.1%-17.9%). CONCLUSIONS: A novel report card was developed on the
      basis of the SHM-CWC pediatric recommendations, including ABCs. We found variance
      in practices among institutions and gaps between hospital performances and ABCs.
      These findings represent a roadmap for improvement.

PMID- 29066471
TI  - Correction: A Transcriptional Program for Detecting TGFbeta-Induced EMT in
      Cancer.

PMID- 29066472
TI  - Mapping Second Chromosome Mutations to Defined Genomic Regions in Drosophila
      melanogaster.
AB  - Hundreds of Drosophila melanogaster stocks are currently maintained at the
      Bloomington Drosophila Stock Center with mutations that have not been associated
      with sequence-defined genes. They have been preserved because they have
      interesting loss-of-function phenotypes. The experimental value of these
      mutations would be increased by tying them to specific genomic intervals so that
      geneticists can more easily associate them with annotated genes. Here, we report
      the mapping of 85 second chromosome complementation groups in the Bloomington
      collection to specific, small clusters of contiguous genes or individual genes in
      the sequenced genome. This information should prove valuable to Drosophila
      geneticists interested in processes associated with particular phenotypes and
      those searching for mutations affecting specific sequence-defined genes.

PMID- 29066469
TI  - Polygenicity and Epistasis Underlie Fitness-Proximal Traits in the Caenorhabditis
      elegans Multiparental Experimental Evolution (CeMEE) Panel.
AB  - Understanding the genetic basis of complex traits remains a major challenge in
      biology. Polygenicity, phenotypic plasticity, and epistasis contribute to
      phenotypic variance in ways that are rarely clear. This uncertainty can be
      problematic for estimating heritability, for predicting individual phenotypes
      from genomic data, and for parameterizing models of phenotypic evolution. Here,
      we report an advanced recombinant inbred line (RIL) quantitative trait locus
      mapping panel for the hermaphroditic nematode Caenorhabditis elegans, the C.
      elegans multiparental experimental evolution (CeMEE) panel. The CeMEE panel,
      comprising 507 RILs at present, was created by hybridization of 16 wild isolates,
      experimental evolution for 140-190 generations, and inbreeding by selfing for 13
      16 generations. The panel contains 22% of single-nucleotide polymorphisms known
      to segregate in natural populations, and complements existing C. elegans mapping
      resources by providing fine resolution and high nucleotide diversity across > 95%
      of the genome. We apply it to study the genetic basis of two fitness components,
      fertility and hermaphrodite body size at time of reproduction, with high broad
      sense heritability in the CeMEE. While simulations show that we should detect
      common alleles with additive effects as small as 5%, at gene-level resolution,
      the genetic architectures of these traits do not feature such alleles. We instead
      find that a significant fraction of trait variance, approaching 40% for
      fertility, can be explained by sign epistasis with main effects below the
      detection limit. In congruence, phenotype prediction from genomic similarity,
      while generally poor ([Formula: see text]), requires modeling epistasis for
      optimal accuracy, with most variance attributed to the rapidly evolving
      chromosome arms.

PMID- 29066473
TI  - Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1
      Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation.
AB  - The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for
      mono, di, and trimethylation and is linked to active transcription due to the
      euchromatic distribution of these methyl marks and the recruitment of Set1 during
      transcription. However, loss of Set1 results in increased expression of multiple
      classes of genes, including genes adjacent to telomeres and middle sporulation
      genes, which are repressed under normal growth conditions because they function
      in meiotic progression and spore formation. The mechanisms underlying Set1
      mediated gene repression are varied, and still unclear in some cases, although
      repression has been linked to both direct and indirect action of Set1, associated
      with noncoding transcription, and is often dependent on the H3K4me2 mark. We show
      that Set1, and particularly the H3K4me2 mark, are implicated in repression of a
      subset of middle sporulation genes during vegetative growth. In the absence of
      Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the
      associated histone deacetylase Hst1 from chromatin in a locus-specific manner.
      This is linked to increased H4K5ac at these loci and aberrant middle gene
      expression. These data indicate that, in addition to DNA sequence, histone
      modification status also contributes to proper localization of Sum1 Our results
      also show that the role for Set1 in middle gene expression control diverges as
      cells receive signals to undergo meiosis. Overall, this work dissects an
      unexplored role for Set1 in gene-specific repression, and provides important
      insights into a new mechanism associated with the control of gene expression
      linked to meiotic differentiation.

PMID- 29066474
TI  - Transcatheter occlusion of the patent ductus arteriosus in premature infants
      weighing less than 1200 g.
AB  - OBJECTIVES: Over the last few decades different strategies have been proposed to
      treat persistent ductal patency in premature infants. The advent of the Amplatzer
      Duct Occluder II Additional Size (ADOIIAS) provided the potential to close the
      patent ductus arteriosus (PDA). Opinions differ on the significance and treatment
      of PDA in premature neonates. Because surgical ligation and medical therapy both
      have their drawbacks, interventional catheterisation can be considered as an
      alternative means of closing the ductus arteriosus. Our aim was to analyse the
      feasibility, safety and efficacy of this device in premature infants weighing
      <1200 g at procedure. METHODS: Eighteen premature infants underwent transcatheter
      closure. The procedure was performed in the catheterisation laboratory by venous
      cannulation without angiography. The position of the occluder was directed by X
      ray and ultrasound. We looked at procedural details, device size selection,
      complications and short-term and mid-term outcomes. RESULTS: Eighteen infants
      born at gestational ages ranging between 23.6 and 29+6 weeks (mean+/-SD 25+6+/-3
      weeks) underwent transcatheter PDA closure. Their mean age and weight at the time
      of the procedure was 20 days (range 8-44 days) and 980 g (range 680-1200 g),
      respectively. The mean PDA and device waist diameters were 3.2+/-0.6 mm (range
      2.2-4 mm) and 4.5+/-0.6 mm, respectively, and the mean PDA and device lengths
      were 4.3+/-1.2 mm (range 2-10 mm) and 2.5+/-0.9 mm, respectively. Complete
      closure was achieved in all but one patient. There was no device migration. One
      patient developed a left pulmonary artery obstruction. Three infants died. Two
      deaths were related to complications of prematurity and one to the procedure.
      CONCLUSIONS: Transcatheter closure of a PDA is feasible in very low weight
      infants with ADOIIAS and is an alternative to surgery. Success requires perfect
      selection and placement of the occluder.

PMID- 29066475
TI  - Effects of long-term use of the preferential COX-2 inhibitor meloxicam on growing
      pigs.
AB  - Meloxicam, a preferential COX-2 inhibitor, is a commonly used NSAID in pigs.
      Besides having potential side effects on the gastrointestinal tract, this type of
      drug might potentially affect osteogenesis and chondrogenesis, processes relevant
      to growing pigs. Therefore, the effects of long-term meloxicam treatment on
      growing pigs were studied. Twelve piglets (n=6 receiving daily meloxicam 0.4
      mg/kg orally from 48 until 110 days of age; n=6 receiving only applesauce
      (vehicle control)) were subjected to visual and objective gait analysis by
      pressure plate measurements at several time points. Following euthanasia a
      complete postmortem examination was performed and samples of the talus and distal
      tibia, including the distal physis, were collected. Trabecular bone
      microarchitecture was analysed by microCT scanning, bone stiffness by compression
      testing and growth plate morphology using light microscopy. Animals were not lame
      and gait patterns did not differ between the groups. Pathological examination
      revealed no lesions compatible with known side effects of NSAIDs. Trabecular bone
      microarchitecture and growth plate morphology did not differ between the two
      groups. The findings of this in vivo study reduce concerns regarding the long
      term use of meloxicam in young, growing piglets.

PMID- 29066477
TI  - Carcinoma In Situ Involving Sclerosing Adenosis: Seeking the Salient Histological
      Characteristics to Prevent Overdiagnosis.
AB  - Ductal or lobular carcinoma in situ (DCIS/LCIS) can rarely arise from sclerosing
      adenosis (SA). The combination of cytologically malignant cells and the
      infiltrative growth pattern may make it challenging to distinguish it from an
      invasive carcinoma. The authors reviewed 50 consecutive cases of CIS involving SA
      to seek the salient histologic characteristics in order to prevent overdiagnosis.
      The features commonly seen with CIS were the lobular configuration at low
      magnification (94%), uninvolved SA in neighboring tissue (84%), at least focally
      identifiable myoepithelial cells on H&E-stained sections (76%), separate foci of
      unequivocal CIS (58%), associated microcalcifications (54%), and hyaline basement
      membrane surrounding tumor cell nests (48%). The group of DCIS with high nuclear
      grade showed a tendency to occupy the entire lobule of SA, whereas those with non
      high grade were more often partially involving the affected lobule. The presence
      of adjacent separate foci of CIS was more closely related to the DCIS lesions
      when compared to those of LCIS. The finding of an SA lobule entirely involved by
      CIS was signifi-cantly correlated with the presence of an invasive carcinoma;
      this should thus strongly prompt the pathologist to search for other evidence of
      invasion. Awareness of these features is an additional, useful tool for reaching
      a proper diagnosis.

PMID- 29066476
TI  - Role of CDKN2C Fluorescence In Situ Hybridization in the Management of Medullary
      Thyroid Carcinoma.
AB  - Medullary thyroid carcinoma (MTC), an aggressive form of thyroid cancer, occurs
      sporadically in approximately 75% of MTCs. RET and RAS mutations play a role in
      about 40% and 15%, respectively, of sporadic MTCs and are predominant drivers in
      MTC pathways. These mutations are some of the most comprehensively described and
      screened for in MTC patients; however, in recent studies, other mutations in the
      CDKN2C gene (p18) have been implicated in the tumorigenesis of MTC. Comparative
      genomic hybridization analysis revealed that approximately 40% of sporadic MTC
      samples have loss of CDKN2C at chromosome 1p32 in addition to frequent losses of
      CDKN2D (p19) at chromosome 19p13. However, no feasible routine method had been
      established to detect loss of heterozygosity (LOH) of CDKN2C and CD-KN2D The aim
      of this study is to assess the feasibility of using Fluorescence in situ
      Hybridization (FISH) to screen MTC patients for CDKN2C and CDKN2D deletions. We
      subjected 5 formalin-fixed, paraffin-embedded (FFPE) MTC samples with defined
      RET/RAS mutations to dual-color FISH assays to detect loss of CDKN2C and/or
      CDKN2D We prepared spectrum orange probes using the bacterial artificial
      chromosomes RP11-779F9 for CDKN2C (p18) and RP11-177J4 for CDKN2D (p19) and
      prepared spectrum green control probes to the 1q25.2 and 19q11 regions (RP11
      1146A3 and RP11-942P7, respectively). Nine FFPE normal thyroid tissue samples
      were used to establish the cutoff values for the FISH signal patterns. Of the
      five FFPE MTC samples, four and one yielded a positive significant result for
      CDKNN2C loss and CDKN2D loss, respectively. The results of a Clinical Laboratory
      Improvement Amendments validation with a CDKN2C/CKS1B probe set for CDKN2C (p18)
      loss of heterozygosity were 100% concordant with the FISH results obtained in
      this study. Thus, FISH is a fast and reliable diagnostic or prognostic indicator
      of gene loss in MTC.

PMID- 29066478
TI  - Re-evaluation of DNA Index as a Prognostic Factor in Children with Precursor B
      Cell Acute Lymphoblastic Leukemia.
AB  - PURPOSE: We aimed to investigate the prognostic value of DNA index (DI) in
      children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL).
      MATERIALS AND METHODS: From January 2003 to December 2014, 72 children diagnosed
      with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its
      relations with other prognostic factors. RESULTS: The DI cut-point of 1.16 did
      not discriminate significantly the groups between high and low survivals
      (DI>=1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p=0.665). We explored the
      survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61
      1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were
      significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS,
      90.6% vs. 50.0%, p<0.001). CONCLUSIONS: The DI of 1.16 was not a significant cut
      point discriminating the risk group in children with pre-B ALL. However, the DI
      divided by specific ranges of values remained an independent prognostic factor.
      Further studies are warranted to re-evaluate the prognostic value and cut-point
      of DI in children treated with recent treatment protocols.

PMID- 29066479
TI  - Eosinophil Cationic Protein in Patients with Differentiated Thyroid Cancer
      Treated with Radioactive Iodine 131.
AB  - Published data indicate the involvement of eosinophil granulocytes and eosinophil
      cationic protein (ECP) in tumor defense. The aim of this study was to analyze
      serum ECP concentrations in patients with differentiated thyroid cancer (DTC)
      before, 3 days and 7 days after radioactive iodine (131-I) therapy. Association
      of ECP concentrations with histological type of tumor, stage of disease and/or
      levels of selected T-helper 2 (Th2) cytokines was examined. The study population
      included 17 DTC patients and 10 control subjects. ECP was measured by
      fluoroimmunoassay (FIA). Th2 (cytokines interleukin 4 (IL-4), interleukin 5 (IL
      5), and interleukin 13 (IL-13)) were determined by enzyme-linked immunosorbent
      assays (ELISA). We found that ECP values in DTC patients before radioactive
      iodine therapy were approximately two-fold higher than in the controls, but the
      difference was statistically significant only if the patients with DTC and
      associated Hashimoto thyroiditis (HT) were included. There was no correlation
      between the serum concentrations of IL-5 and ECP. Radioactive iodine therapy led
      to a decrease in serum ECP level which did not follow the decline in serum
      protein levels. Additional studies are needed to determine the significance of
      these findings.

PMID- 29066480
TI  - Detection of the Single Nucleotide Polymorphism at Position rs2735940 in the
      Human Telomerase Reverse Transcriptase Gene by the Introduction of a New
      Restriction Enzyme Site for the PCR-RFLP Assay.
AB  - It has been shown that the single nucleotide polymorphism (SNP) of the rs2735940
      site in the human telomerase reverse transcriptase (hTERT) gene is associated
      with increased cancer risk. The traditional method to detect SNP genotypes is
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      However, there is a limitation to utilizing PCR-RFLP due to a lack of proper
      restriction enzyme sites at many polymorphic loci. This study used an improved
      PCR-RFLP method with a mismatched base for detection of the SNP rs2735940. A new
      restriction enzyme cutting site was created by created restriction site PCR (CRS
      PCR), and in addition, the restriction enzyme MspI for CRS-PCR was cheaper than
      other enzymes. We used this novel assay to determine the allele frequencies in
      552 healthy Chinese Han individuals, and found the allele frequencies to be 63%
      for allele C and 37% for allele T In summary, the modified PCR-RFLP can be used
      to detect the SNP of rs2735940 with low cost and high efficiency.

PMID- 29066481
TI  - Acetylsalicylic Acid During Leukapheresis Reduces the Incidence of Clotting in
      Hematopoietic Progenitor Cell Products.
AB  - INTRODUCTION: Clots may be seen during hematopoietic progenitor cell (HPC)
      collection or on product arrival to the cell therapy processing laboratory. We
      have always given one 81 mg acetylsalicylic acid (ASA) when clotting is seen
      during collection if there is no allergy, but hypothesized that the incidence of
      clotting would decrease if ASA was given to all autologous collectors with a
      platelet count of >=80*109/L prior to collection (pre-emptively). METHODS:
      Autologous HPC were collected using the Spectra Optia instrument or Cobe Spectra
      instrument (Terumo BCT(r), Lakewood, CO) with heparinized citrate. A
      retrospective review was performed to determine the total number of HPC products,
      including products with clots, collected between September 2010 and August 2013
      (group 1). All autologous HPC collectors from September 2013 onwards were given
      ASA pre-emptively if their platelet count was >=80*109/L (group 2), and a similar
      review was performed in this group. We included the cell density and platelet
      count of the HPC products and the platelet count of the patient in the data
      collected. We reviewed procedure notes for adverse events or bleeding. RESULTS: A
      total of 2574 HPC products were collected between September 2010 and August 2013;
      clotting was observed in 66 HPC products (66/2574; 2.56%). A total of 1906 HPC
      products were collected between November 2013 and October 2016; clotting was
      observed in 24 HPC products (24/1906; 1.25%). Thus an overall reduction was seen
      in incidence of clotting between groups 1 and 2 (2.56% versus 1.25; P=0.002).
      Since not all collectors in group 2 received pre-emptive ASA, we reviewed the
      incidence of clotting within this group. A decrease in incidence of clots was
      noted with preemptive ASA (group 2A) (5/512, 0.97%) versus no ASA (group 2B)
      (19/1394, 1.36%), but this was not statistically significant. The mean cell
      density of the HPC products did not differ significantly between these two groups
      (group 2A and 2B) but a higher platelet count was observed in the pre-emptive ASA
      group as expected (group 2A) (P=0.004). Multivariate logistic analysis after
      adjusting for platelet count of the HPC products showed a trend towards reduced
      incidence of clotting in the pre-emptive ASA group (group 2A); however no
      association was seen after adjusting for the cell density of HPC products, nor
      was an association between patient's platelet count and incidence of clotting
      seen. None of the collectors who received ASA suffered any adverse events,
      including bleeding. CONCLUSION: We observed an overall reduction in the incidence
      of clotting in our HPC products after initiating pre-emptive ASA usage (2.56%
      versus 1.25%; P=0.002). A trend towards lower incidence of clotting was noted
      when further analysis was performed to include pre-emptive ASA usage and platelet
      count of the HPC products. Although the overall incidence of clotting was very
      small (<3.0%), giving ASA pre-emptively further reduced the incidence of clotting
      and thus prevented wastage/cell loss of HPC products.

PMID- 29066482
TI  - The Effect of Metformin on the Expression of GPR109A, NF-kappaB and IL-1beta in
      Peripheral Blood Leukocytes from Patients with Type 2 Diabetes Mellitus.
AB  - OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), which often accompanies
      dyslipidemia, is considered an inflammatory disease. GPR109A, as a niacin
      receptor, is up-regulated under high glucose concentration. Activation of GPR109A
      reduces GSIS and exerts anti-inflammatory effects by regulating NF-kappaB/IL
      1beta signaling. Metformin improves hyperglycemia, increases insulin sensitivity
      and attenuates the activation of the NF-kappaB pathway in T2DM. We aimed to
      examine whether metformin plays beneficial effects in T2DM by regulating the
      GPR109A signaling. METHODS: 117 T2DM patients were involved in this study and
      divided into two groups, the control group (without metformin) and the Metformin
      (Met) group (orally given metformin, 500mg-2000mg/d). Peripheral blood samples
      were collected from all the patients for testing PBL counts, biochemical data,
      and C peptide. Total RNA was isolated from PBLs. RT-PCR and immunocytochemistry
      were used to examine the expression of GPR109A, NF-kappaB and IL-1beta in PBLs.
      RESULTS: FPG, HbA1c and LDL levels were lower and 2hr C peptide was higher in the
      Met group than in the control group (P<0.05). RT-PCR showed that mRNA levels of
      GPR109A, NF-kappaB and IL-1beta were lower in the Met group than in the control
      group (P<0.05). Correlation analysis showed that there was a positive correlation
      between GPR109A and IL-1beta (p<0.01, r=0.425) in the control group, GPR109A and
      IL-1beta (p<0.05, r=0.256), GPR109A, and NF-kappaB (p<0.05,r=0.295) in the Met
      group. Immunocytochemistry showed that the GPR109A and NF-kappaB proteins were
      localized in the nucleus and cytoplasm of PBLs; however, there were no
      significant differences in the protein expression between the two groups.
      CONCLUSIONS: The results suggest that Met may reduce GPR109A expression in PBLs
      of T2DM patients by suppressing NF-kappaB/IL-1beta signaling. Up-regulated
      expression of GPR109A may be an inflammatory consequence and the improvement of
      inflammation may down-regulate the expression of GPR109A in T2DM.

PMID- 29066484
TI  - Aminoguanidine (AG) Induces Induced both Pro- and Antioxidant Effect in AR42J
      Cells, a Rat Pancreatic Tumor Cell Line.
AB  - : Aminoguanidine (AG), a diamine oxidase and a nitric oxide synthase inhibitor,
      was used in diabetes, thyroid follicular carcinoma, hepatocellular carcinoma,
      pancreatic cancer xenografts and in breast cancer research. The effects of AG on
      these pathologic conditions may be related to its regulatory effects on cell
      proliferation, angiogenesis, and expression of antioxidant enzymes. However, its
      role as pro and/or anti-oxidant affecting signaling and function in pancreatic
      tumor cell lines has not been studied. The current study tested the hypothesis
      that exposure of AR42J cells to aminoguanidine will induce pro-oxidant effects
      that may lead to increased proliferation and growth of these cells. METHODS:
      AR42J cells were grown in F-12 nutrient medium in 5% CO2 at 37 degrees C to
      attain over 90% confluency before being treated with 20 uM hydrogen peroxide
      (H2O2) for 20 min and 100 uM AG for 30 min separately and in combination. Cell
      lysates collected from these experiments were measured for formation of lipid
      peroxides by malondialdehyde (MDA) assay and for activation of phospho-ERK 1/2
      signal transduction by Western blotting. The activation of ERK signaling was
      further confirmed by immunohistochemical analysis. Effect of ERK1/2 on cell
      proliferation in response to AG and H2O2 was evaluated by MTT assay while the
      functional status of AR42J cells was determined by release of amylase following
      CCK-8 stimulation. RESULTS: MDA concentration in cells treated with AG was not
      different from untreated cells. However, treatment with H2O2 either alone or in
      combination with AG increased MDA significantly (p<0.05). AG treatment alone
      induced 3.5 fold activation of pERK-1/2, as compared to 2.5 fold increase with
      H2O2 alone (p<0.05) as compared to untreated control. The results of ERK
      activation were confirmed further by its co-localization employing FITC
      conjugated ERK antibody. AG -induced maximal cell proliferation occurred at 48
      hr. incubation (p<0.05); these values were not significantly different from that
      of H2O2 treated and control cells. Cell function (CCK-stimulated amylase release)
      was significantly enhanced by AG (p<0.05). CONCLUSION: These data suggest that in
      an in-vitro system, AG acts as a pro-oxidant on AR42J cell proliferation and
      possibly affects the resulting function.

PMID- 29066483
TI  - Aquaporin-4 Blockage by siRNA Protects Rat Articular Chondrocytes from IL-1beta
      induced Apoptosis by Inhibiting p38 MAPK Signal Pathway.
AB  - Accumulating evidence reveals that articular chondrocytes undergo increased
      apoptosis in rheumatoid arthritis (RA) and inhibiting chondrocyte apoptosis might
      be a promising therapeutic strategy. We recently found that aquaporin-4 (AQP4)
      protein level in the cartilage of rats with adjuvant-induced arthritis was higher
      than normal rats. Herein, cultured rat articular chondrocyte impaired by
      interleukin-1 beta (IL-1beta) was used as an in vitro model of chondrocyte
      apoptosis. We observed the protective effect of AQP4 blockage by siRNA on IL
      1beta-induced chondrocyte apoptosis and explored the underlying mechanisms. Our
      findings revealed that AQP4 siRNA protected articular chondrocytes from IL-1beta
      induced apoptosis, evidenced by increased cell proliferation (MTT assay), few
      observations of apoptotic morphologic changes (Hoechst 33258 staining assay) and
      decreased cell apoptosis rates (Annexin V-FITC/PI staining assay). Additionally,
      AQP4 siRNA remarkably decreased Bax and caspase 3 mRNA levels and increased Bcl-2
      mRNA level, accompanied by reducing phosphorylated-p38 (P-p38) protein level,
      without affecting p38 protein. The above effects of AQP4 siRNA were similar to
      SB203580, a specific p38 inhibitor. Together, AQP4 siRNA attenuated IL-1beta
      induced chondrocyte apoptosis by regulating apoptosis-related gene expressions
      and inhibiting p38 MAPK. Our results provide experimental evidence that AQP4
      inhibition contributes to preventing chondrocyte apoptosis in joint diseases such
      as RA and provide a novel therapeutic target for RA.

PMID- 29066485
TI  - New Alert Message Settings for the XN-series Automated Hematology Analyzer Are
      Useful for Avoiding Falsely High WBC Counts and to Detect Specimens with Giant
      Platelets.
AB  - We encountered blood specimens from a patient with MYH9 related diseases, which
      gave falsely high white blood cell (WBC) counts during laboratory analysis using
      Sysmex XN-series automated hematology analyzers. This overcount was revealed to
      be caused by the overlapping of platelet (PLT) distribution with the WBC area in
      the WNR channel, which was used for routine WBC count with the XN-series. On the
      other hand, the WBC count obtained through the WDF channel of the XN-series
      seemed more accurate in such a case. We then created and introduced alert message
      settings for such rare but critical specimens, which gives a warning when the
      discrepancy in WBC counts between the WNR and WDF channels is higher than
      1.0*109/L. By using the alert message setting, we were able to detect some
      specimens which gave falsely high WBC counts with the routine WNR channel from
      three other cases of giant PLTs. In conclusion, our alert message setting seems
      useful in avoiding false reporting of WBC count due to abnormal cells, including
      giant PLTs.

PMID- 29066487
TI  - Early Antibody Response Contributes to the Virus Eradication and Clinical
      Recovery of H7N9 Influenza Infection.
AB  - A new type of highly pathogenic avian influenza virus, H7N9, has been a great
      threat to public health since its 2013 outbreak. The humoral immune response
      plays a critical role in protection from the influenza virus, but its role and
      kinetics in H7N9-infected patients remain to be determined. In this study, we
      performed a retrospective investigation of the antibody response in plasma
      samples from 37 cases of hospitalized patients and analysed the relationship
      between the antibody response and the clinical outcomes. Our results showed that
      the HA7-binding antibody was generated earlier than the neutralizing antibody.
      Higher titer of HA7-binding antibody during the first 14 days after disease onset
      were associated with a shorter virus-positive continuation period, which is an
      important risk predictor (P<0.05). Additionally, the titers of HA7-binding
      antibody were consistently and significantly lower in patients who died than
      those who recovered from the severe disease. Unexpectedly, no correlation between
      the titer of neutralizing antibody and the resulting clinical outcomes was found,
      suggesting that a neutralizing antibody-independent mechanism also contributed to
      virus control. In summary, our data suggests that an early antibody response
      against H7N9 influenza virus contributes to the eradication of the virus. A
      higher, early HA7-binding antibody response is associated with better clinical
      outcomes in H7N9 patients.

PMID- 29066486
TI  - Serum Uric Acid Levels and Risk of Incident Hypertriglyceridemia: A Longitudinal
      Population-based Epidemiological Study.
AB  - BACKGROUND: Hypertriglyceridemia is one of lipid metabolism abnormalities;
      however, it is still debatable whether serum uric acid is a cause or a
      consequence of hypertriglyceridemia. We performed the study to investigate the
      longitudinal association between serum uric acid levels and hypertriglyceridemia.
      METHODS: The study included 4190 subjects without hypertriglyceridemia. The
      subjects had annual health examinations for 8 years to assess incident
      hyperglyceridemia, and the subjects were divided into groups based on the serum
      uric acid quartile. Cox regression models were used to analyze the risk factors
      of development hypertriglyceridemia. RESULTS: During follow-up, 1461 (34.9%)
      subjects developed hypertriglyceridemia over 8 years of follow-up. The cumulative
      incidence of hypertriglyceridemia was 28.2%, 29.1%, 36.9%, and 45.6% in quartile
      1,2,3 and 4, respectively (P for trend <0.001). Cox regression analyses indicated
      that serum uric acid levels were independently and positively associated with the
      risk of incident hypertriglyceridemia. CONCLUSIONS: Hypertriglyceridemia has
      become a serious public health problem. This longitudinal study demonstrates that
      high serum uric acid levels increase the risk of hypertriglyceridemia.

PMID- 29066489
TI  - Demodex as a Delivery Vector for Topical Targeted Medications in the Skin for
      Early Melanoma and Non-Melanoma Skin Cancer.
AB  - The potential utilization of Demodex mites as delivery vectors for cytotoxic
      medications directed to early skin cancer is proposed. Potential benefits, proof
      of concept, and limitations are discussed.

PMID- 29066488
TI  - Can Tranexamic Acid Reduce Blood Loss during Major Cardiac Surgery? A Pilot
      Study.
AB  - We examined the effectiveness of tranexamic acid in preventing intraoperative
      blood loss during major cardiac surgery. Out of initial 81 patients undergoing
      major cardiac surgery (both coronary artery bypass and valve repair procedures)
      at our teaching hospital, sixty-seven patients were selected for this study. We
      compared estimated blood loss, decrease in percent hemoglobin and hematocrit
      following surgery between two groups of patients (none of them received any blood
      product during surgery), one group receiving no tranexamic acid (n=17) and
      another group receiving tranexamic acid (n=25). In the second study, we combined
      these patients with patients receiving modest amounts of blood products (1-2
      unit) and compared these parameters between two groups of patients (25 patients
      received no tranexamic acid, 42 patients received tranexamic acid). In patients
      who received no blood product during surgery, those who received no tranexamic
      acid showed statistically significant (independent t-test two tailed at p<0.05)
      reduced estimated blood loss (mean: 713.5 mL, SD: 351.6, n=17) compared to those
      who received tranexamic acid (mean: 987.2 mL, SD: 459.9, n=25). We observed
      similar results when the patients receiving no blood products and patients
      receiving modest amount of blood products were combined based on the use of
      tranexamic acid or not. No statistically significant difference was observed in
      percent reduced hemoglobin or hematocrit following surgery in any group of
      patients. We conclude that intraoperative antifibrinolytic therapy with
      tranexamic acid does not reduce intraoperative blood loss during major cardiac
      surgery which contradicts popular belief.

PMID- 29066490
TI  - Novel Germline p.Gly42Val MEN1 Mutation in a Family with Multiple Endocrine
      Neoplasia Type 1 - Excellent Response of Prolactinoma to Cabergoline.
AB  - We report on a 27-year-old male patient presenting with renal colic secondary to
      hyperparathyroidism. Further investigations confirmed a diagnosis of type 1
      multiple endocrine neoplasia and revealed a 2.0 cm pancreatic neuroendocrine
      tumour as well as a pituitary macroadenoma with significantly elevated prolactin
      levels. The patient underwent three-gland parathyroidectomy, a left
      pancreatectomy, and received dopamine agonist treatment. Genetic testing revealed
      a novel germline heterozygote missense mutation in the MEN1 gene (p.Gly42Val)
      which affects the Smad3 binding domain of the MENIN protein. The same mutation
      was found in the patient's mother, who on further testing was found to have
      hyperparathyroidism, a pituitary microadenoma and bilateral adrenal hyperplasia
      without pituitary or adrenal hormone excess. This case report raises the
      importance of genetic testing for MEN1 syndrome in a patient even when family
      history appears to be negative. Following genetic counselling, genetic cascade
      screening should be considered in family members to identify further gene
      carriers.

PMID- 29066491
TI  - IgM Myeloma with Plasma Cell Leukemia: Case Report and Literature Review.
AB  - IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all
      MM. It should be distinguished from malignant neoplasms of B cells with
      plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and
      marginal zone lymphoma with plasmacytic differentiation. Plasma cell leukemia
      (PCL) is a rare and aggressive variant of MM characterized by the presence of
      circulating plasma cells. We present a case report of a patient who presented
      with IgM MM in primary PCL phase with high-risk cytogenetics. To our knowledge,
      this is the first reported case of IgM MM with primarily leukemic presentation in
      the era of novel drugs. We demonstrate that it is important to distinguish IgM MM
      from WM and review the data from clinical trials that was used to devise a
      treatment strategy for this high-risk patient. This case adds to the
      understanding of the diagnosis and management of IgM MM in leukemic phase.

PMID- 29066492
TI  - Granulomatous Thyroiditis: A Case Report and Literature Review.
AB  - BACKGROUND: Granulomatous disease in the thyroid gland has been linked to viral,
      bacterial and autoimmune etiologies. The most common granulomatous disease of the
      thyroid is subacute granulomatous thyroiditis, which is presumed to have a viral
      or post-viral inflammatory cause. Bacterial etiologies include tuberculosis,
      actinomycosis, and nocardiosis, but are extremely rare. Disseminated
      actinomycosis and nocardiosis more commonly affect organ-transplant patients with
      the highest susceptibility within the first year after transplant surgery. CASE:
      A 45-year-old African American male, who received his third kidney transplant for
      renal failure secondary to Alport Syndrome, presented with numerous subcutaneous
      nodules and diffuse muscle pain in the neck. Further workup revealed bilateral
      nodularity of the thyroid. Fine needle aspiration of these nodules demonstrated
      suppurative granulomatous thyroiditis. Subsequent right thyroid lobectomy showed
      granulomatous thyroiditis with filamentous micro-organisms, morphologically
      resembling Nocardia or Actinomyces. CONCLUSION: Disseminated granulomatous
      disease presenting in the thyroid is very rare, and typically afflicts immune
      compromised patients. The overall clinical, cytologic and histologic picture of
      this patient strongly points to an infectious etiology, likely Nocardia, in the
      setting of recent organ transplantation within the last year.

PMID- 29066493
TI  - Capillarys 2 Flex Piercing Detected a Rare Case of Hb Broomhill.
AB  - We report a case of an extremely rare hemoglobin (Hb) variant-Hb Broomhill, which
      has been only reported once in the literature. Hemoglobin fractions were
      determined by capillary electrophoresis (Sebia Capillarys 2 Flex piercing) and
      high performance liquid chromatography (HPLC) (Bio-Rad VariantTM II Hemoglobin
      Testing System), respectively. Complete blood count and DNA sequencing were also
      performed. The capillary electrophoregram revealed a tiny shoulder peak before
      the HbA peak and a subtle abnormal HbA2 peak (slightly wider and lower), even
      though the percentage of each hemoglobin fraction was within the reference range
      (HbA, 97.4%; HbA2, 2.6%). On HPLC, not only the percentage but also the peak
      shape of each hemoglobin fraction was normal (HbA 88.2%, HbA2 2.5%, HbF 0.6%).
      Eventually, sequencing analysis of alpha genes confirmed a missense mutation
      (CCC>GCC at codon 114 in alpha1 gene) which caused Hb Broomhill variant. Our
      report suggest that capillary electrophoresis may be an accurate tool for
      screening and diagnosis of Hb disorders.

PMID- 29066495
TI  - Discordant Analytical Results Caused by Biotin Interference on Diagnostic
      Immunoassays in a Pediatric Hospital.
AB  - Recent studies have reported that biotin interferes with certain immunoassays. In
      this study, we evaluated the analytical interference of biotin on immunoassays
      that use streptavidin-biotin in our pediatric hospital. We tested the effect of
      different concentrations of biotin (1.5-200 ng/ml) on TSH, Prolactin, Ferritin,
      CK-MB, beta-hCG, Troponin I, LH, FSH, Cortisol, Anti-HAV antibody (IgG and IgM),
      assays on Ortho Clinical Diagnostic Vitros 5600 Analyzer. Biotin (up to 200
      ng/mL) did not significantly affect Troponin I and HAV assays. Biotin (up to 12.5
      ng/ml) resulted in <10% bias in CK-MB, beta-hCG, AFP, Cortisol, Ferritin assays
      and biotin >6.25 ng/mL significantly affected TSH (>20% bias) assay. Prolactin
      was significantly affected even at low levels (Biotin 1.5 ng/mL). Thus, we
      recommend educating physicians about biotin interference in common immunoassays
      and adding an electronic disclaimer.

PMID- 29066494
TI  - Vitamin D Receptor ApaI (rs7975232) Polymorphism Confers Decreased Risk of
      Pulmonary Tuberculosis in Overall and African Population, but not in Asians:
      Evidence from a Meta-analysis.
AB  - GOALS: The involvement of the VDR ApaI gene polymorphism in the development of
      pulmonary tuberculosis (PTB) has been reported by numerous published studies and
      yielded inconsistent results. The present meta-analysis evaluated the association
      of VDR ApaI polymorphism and risk of PTB occurrence. PROCEDURES: PubMed
      (Medline), EMBASE and Google Scholar web-databases were searched and a meta
      analysis was performed by calculating the pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs). RESULTS: This meta-analysis included a total of
      14 eligible studies comprising of 1958 confirmed PTB cases and 2938 controls. We
      observed decreased risk of PTB in allelic (a vs. A: p=0.003; OR=0.873, 95%
      CI=0.798 to 0.955), homozygous (aa vs. AA: p=0.006; OR=0.761, 95% CI=0.626 to
      0.924), dominant (aa+Aa vs. AA: p=0.039; OR=0.874, 95% CI=0.769 to 0.993) and
      recessive (aa vs. AA+Aa: p=0.025; OR=0.819, 95% CI=0.688 to 0.975) genetic
      models. During subgroup analysis, allele (a vs. A: p=0.005; OR=0.846, 95%
      CI=0.753 to 0.951), homozygous (aa vs. AA: p=0.002; OR=0.662, 95% CI=0.513 to
      0.854) and recessive genetic models (aa vs. AA+Aa: p=0.003; OR=0.709, 95%
      CI=0.566 to 0.889) demonstrated decreased PTB risk in African population.
      However, no significant association was observed in Asian population. CONCLUSION:
      In conclusion, VDR ApaI polymorphism is significantly associated with decreased
      risk of PTB for in overall and African population, but not in Asians.

PMID- 29066496
TI  - Locum pay is up by 6% after tax change.

PMID- 29066498
TI  - Examining the role of healthcare professionals in the use of solitary
      confinement.

PMID- 29066497
TI  - T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal
      Adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy resistant to most
      therapies, including immune checkpoint blockade. To elucidate mechanisms of
      immunotherapy resistance, we assessed immune parameters in resected human PDA. We
      demonstrate significant interpatient variability in T-cell number, localization,
      and phenotype. CD8+ T cells, Foxp3+ regulatory T cells, and PD-1+ and PD-L1+
      cells were preferentially enriched in tertiary lymphoid structures that were
      found in most tumors compared with stroma and tumor cell nests. Tumors containing
      more CD8+ T cells also had increased granulocytes, CD163+ (M2 immunosuppressive
      phenotype) macrophages, and FOXP3+ regulatory T cells. PD-L1 was rare on tumor
      cells, but was expressed by CD163+ macrophages and an additional stromal cell
      subset commonly found clustered together adjacent to tumor epithelium. The
      majority of tumoral CD8+ T cells did not express molecules suggestive of recent T
      cell receptor (TCR) signaling. However, 41BB+PD-1+ T cells were still
      significantly enriched in tumors compared with circulation. Tumoral CD8+PD-1+ T
      cells commonly expressed additional inhibitory receptors, yet were mostly T-BEThi
      and EOMESlo, consistent with a less terminally exhausted state. Analysis of gene
      expression and rearranged TCR genes by deep sequencing suggested most patients
      have a limited tumor-reactive T-cell response. Multiplex immunohistochemistry
      revealed variable T-cell infiltration based on abundance and location, which may
      result in different mechanisms of immunotherapy resistance. Overall, the data
      support the need for therapies that either induce endogenous, or provide
      engineered, tumor-specific T-cell responses, and concurrently relieve suppressive
      mechanisms operative at the tumor site. Cancer Immunol Res; 5(11); 978-91.
      (c)2017 AACR.

PMID- 29066499
TI  - A mutually exclusive stem-loop arrangement in roX2 RNA is essential for X
      chromosome regulation in Drosophila.
AB  - The X chromosome provides an ideal model system to study the contribution of RNA
      protein interactions in epigenetic regulation. In male flies, roX long noncoding
      RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin
      ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X
      chromosomal regulation. However, how these interactions provide the mechanics of
      spreading remains unknown. By using the uvCLAP (UV cross-linking and affinity
      purification) methodology, which provides unprecedented information about RNA
      secondary structures in vivo, we identified the minimal functional unit of roX2
      RNA. By using wild-type and various MLE mutant derivatives, including a
      catalytically inactive MLE derivative, MLEGET, we show that the minimal roX RNA
      contains two mutually exclusive stem-loops that exist in a peculiar structural
      arrangement: When one stem-loop is unwound by MLE, an alternate structure can
      form, likely trapping MLE in this perpetually structured region. We show that
      this functional unit is necessary for dosage compensation, as mutations that
      disrupt this formation lead to male lethality. Thus, we propose that roX2 lncRNA
      contains an MLE-dependent affinity switch to enable reversible interactions of
      the MSL complex to allow dosage compensation of the X chromosome.

PMID- 29066502
TI  - ROS-induced near-homozygous genomes in thyroid cancer.
AB  - A near-homozygous genome (NHG) is especially seen in a subset of follicular
      thyroid cancer of the oncocytic type (FTC-OV). An NHG was also observed in the
      metabolically relatively quiescent cell lines XTC.UC1, a model for FTC-OV, and in
      FTC-133, -236 and -238, the latter three derived from one single patient with
      follicular thyroid cancer. FTC-236 subclones showed subtle whole-chromosome
      differences indicative of sustained reciprocal mitotic missegregations. Reactive
      oxygen species (ROS) scavenger experiments reduced the number of chromosomal
      missegregations in XTC.UC1 and FTC-236, while pCHK2 was downregulated in these
      cells. Treatment with antimycin A increased ROS indicated by enhanced MitoSOX Red
      and pCHK2 fluorescence in metaphase cells. In a selected set of oncocytic
      follicular thyroid tumors, increasing numbers of whole-chromosome losses were
      observed toward an aggressive phenotype, but with retention of chromosome 7.
      Together, ROS activates CHK2 and links to the stepwise loss of whole chromosomes
      during tumor progression in these lesions. We postulate that sequential loss of
      whole chromosomes is a dominant driver of the oncogenesis of a subset of
      follicular thyroid tumors.

PMID- 29066501
TI  - Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian
      cancer cells.
AB  - Clinical implications of the BRCA2 expression level on treatments of ovarian
      cancer are controversial. Here, we demonstrated that platinum-resistant cancer
      had a higher percentage of high BRCA2 level (87.5% vs 43.6%, P = 0.001), and that
      patients with a low BRCA2 level in cancer tissues had longer progression-free
      survival (with a median time of 28.0 vs 12.0 months, P < 0.001) and platinum-free
      duration (with a median time of 19.0 vs 5.0 months, P < 0.001) compared with
      those with a high BRCA2 level. In human ovarian cancer cell lines CAOV-3 and ES
      2, cisplatin induced an upregulation of the RAD51 protein, which was inhibited
      after silencing BRCA2; silencing BRCA2 enhanced the action of cisplatin in vitro
      and in vivo Knockdown of BRCA2 promoted cisplatin-induced autophagy.
      Interestingly, the autophagy blocker chloroquine enhanced cisplatin in BRCA2
      silenced cells accompanied by an increase in apoptotic cells, which did not occur
      in BRCA2-intact cells; chloroquine enhanced the efficacy of cisplatin against
      BRCA2-silenced CAOV-3 tumors in vivo, with an increase in LC3-II level in tumor
      tissues. Sensitization of cisplatin was also observed in BRCA2-silenced CAOV-3
      cells after inhibiting ATG7, confirming that chloroquine modulated the
      sensitivity via the autophagy pathway. These data suggest that a low BRCA2 level
      can predict better platinum sensitivity and prognosis, and that the modulation of
      autophagy can be a chemosensitizer for certain cancers.

PMID- 29066500
TI  - Suppression of protein tyrosine phosphatase N23 predisposes to breast
      tumorigenesis via activation of FYN kinase.
AB  - Disruption of the balanced modulation of reversible tyrosine phosphorylation has
      been implicated in the etiology of various human cancers, including breast
      cancer. Protein Tyrosine Phosphatase N23 (PTPN23) resides in chromosomal region
      3p21.3, which is hemizygously or homozygously lost in some breast cancer
      patients. In a loss-of-function PTPome screen, our laboratory identified PTPN23
      as a suppressor of cell motility and invasion in mammary epithelial and breast
      cancer cells. Now, our TCGA (The Cancer Genome Atlas) database analyses
      illustrate a correlation between low PTPN23 expression and poor survival in
      breast cancers of various subtypes. Therefore, we investigated the tumor
      suppressive function of PTPN23 in an orthotopic transplantation mouse model.
      Suppression of PTPN23 in Comma 1Dbeta cells induced breast tumors within 56 wk.
      In PTPN23-depleted tumors, we detected hyperphosphorylation of the
      autophosphorylation site tyrosine in the SRC family kinase (SFK) FYN as well as
      Tyr142 in beta-catenin. We validated the underlying mechanism of PTPN23 function
      in breast tumorigenesis as that of a key phosphatase that normally suppresses the
      activity of FYN in two different models. We demonstrated that tumor outgrowth
      from PTPN23-deficient BT474 cells was suppressed in a xenograft model in vivo
      upon treatment with AZD0530, an SFK inhibitor. Furthermore, double knockout of
      FYN and PTPN23 via CRISPR/CAS9 also attenuated tumor outgrowth from PTPN23
      knockout Cal51 cells. Overall, this mechanistic analysis of the tumor-suppressive
      function of PTPN23 in breast cancer supports the identification of FYN as a
      therapeutic target for breast tumors with heterozygous or homozygous loss of
      PTPN23.

PMID- 29066503
TI  - Chromogranin A as circulating marker for diagnosis and management of
      neuroendocrine neoplasms: more flaws than fame.
AB  - Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability
      of reliable circulating markers is critical for improving diagnostics, prognostic
      stratification, follow-up and definition of treatment strategy. This review is
      focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large
      dense core vesicles of neuroendocrine cells. Despite being long identified as the
      most useful NEN-related circulating marker, clinical application of CgA is
      controversial. CgA assays still lack standardization, thus hampering not only
      clinical management but also the comparison between different analyses. In the
      diagnostic setting, clinical utility of CgA is limited as hampered by (a) the
      variety of oncological and non-oncological conditions affecting marker levels,
      which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA,
      which impairs sensitivity. Regarding the prognostic phase, there is prospective
      evidence which demonstrates that advanced NENs secreting CgA have poorer outcome,
      as compared with those showing non-elevated marker levels. Although the
      identification of cut-offs allowing a proper risk stratification of CgA-secreting
      patients has not been performed, this represents the most important clinical
      application of the marker. By contrast, based on prospective studies, the trend
      of elevated circulating CgA does not represent a valid indicator of morphological
      evolution and has therefore no utility for the follow-up phase. Ultimately,
      current knowledge about the role of the marker for the definition of treatment
      strategy is poor and is limited by the small number of available studies, their
      prevalent retrospective nature and the absence of control groups of untreated
      subjects.

PMID- 29066504
TI  - Patient quality of life and prognosis in multiple endocrine neoplasia type 2.
AB  - Multiple endocrine neoplasia type 2 (MEN2) refers to the autosomal-dominant
      neuroendocrine tumour syndromes, MEN type 2A (MEN2A) and MEN type 2B (MEN2B).
      They are typified by the development of medullary thyroid cancer (MTC),
      phaeochromocytoma and parathyroid hyperplasia in MEN2A and MTC,
      phaeochromocytomas, ganglioneuromatosis and skeletal abnormalities in MEN2B. The
      aggressiveness of MTC is variable according to genotype, and although it is still
      the major cause of mortality in both conditions, prognosis has improved
      dramatically in those diagnosed and treated at a young age thanks to predictive
      genetic testing. Nevertheless, metastatic MTC, ganglioneuromatosis and a variety
      of other negative clinical and psychosocial impacts on quality of life and/or
      prognosis in MEN2 persist. In the absence, at the time of writing, of any large
      scale research into quality of life specifically in MEN2, this review includes
      data from patient surveys and anonymised patient anecdotes from the records of
      the Association for Multiple Endocrine Neoplasia Disorders (AMEND), for whom the
      authors work. We recommend that these patients are cared for only in centres of
      expertise able to provide expert diagnosis, treatment and continuity of care,
      including psychological and transition support. Only in this way can the clinical
      advances of the last two and half decades be built upon further to ensure that
      the care of these complex, lifelong patients can be considered truly holistic.

PMID- 29066505
TI  - A Phase I Open-Label Study to Identify a Dosing Regimen of the Pan-AKT Inhibitor
      AZD5363 for Evaluation in Solid Tumors and in PIK3CA-Mutated Breast and
      Gynecologic Cancers.
AB  - Purpose: This phase I, open-label study (Study 1, D3610C00001; NCT01226316) was
      the first-in-human evaluation of oral AZD5363, a selective pan-AKT inhibitor, in
      patients with advanced solid malignancies. The objectives were to investigate the
      safety, tolerability, and pharmacokinetics of AZD5363, define a recommended
      dosing schedule, and evaluate preliminary clinical activity.Experimental Design:
      Patients were aged >=18 years with World Health Organization (WHO) performance
      status of 0 to 1. Dose escalation was conducted within separate continuous and
      intermittent [4 days/week (4/7) or 2 days/week (2/7)] schedules with safety,
      pharmacokinetic, and pharmacodynamic analyses. Expansion cohorts of approximately
      20 patients each explored AZD5363 activity in PIK3CA-mutant breast and
      gynecologic cancers.Results: MTDs were 320, 480, and 640 mg for continuous (n =
      47), 4/7 (n = 21), and 2/7 (n = 22) schedules, respectively. Dose-limiting
      toxicities were rash and diarrhea for continuous, hyperglycemia for 2/7, and none
      for 4/7. Common adverse events were diarrhea (78%) and nausea (49%) and, for
      Common Terminology Criteria for Adverse Events grade >=3 events, hyperglycemia
      (20%). The recommended phase II dose (480 mg bid, 4/7 intermittent) was assessed
      in PIK3CA-mutant breast and gynecologic expansion cohorts: 46% and 56% of
      patients, respectively, showed a reduction in tumor size, with RECIST responses
      of 4% and 8%. These responses were less than the prespecified 20% response rate;
      therefore, the criteria to stop further recruitment to the PIK3CA-mutant cohort
      were met.Conclusions: At the recommended phase II dose, AZD5363 was well
      tolerated and achieved plasma levels and robust target modulation in tumors.
      Proof-of-concept responses were observed in patients with PIK3CA-mutant cancers
      treated with AZD5363. Clin Cancer Res; 24(9); 2050-9. (c)2017 AACRSee related
      commentary by Costa and Bosch, p. 2029.

PMID- 29066506
TI  - Chemical Profiling of Primary Mesothelioma Cultures Defines Subtypes with
      Different Expression Profiles and Clinical Responses.
AB  - Purpose: Finding new treatment options for patients with malignant pleural
      mesothelioma is challenging due to the rarity and heterogeneity of this cancer
      type. The absence of druggable targets further complicates the development of new
      therapies. Current treatment options are therefore limited, and prognosis remains
      poor.Experimental Design: We performed drug screening on primary mesothelioma
      cultures to guide treatment decisions of corresponding patients that were
      progressive after first- or second-line treatment.Results: We observed a high
      concordance between in vitro results and clinical outcomes. We defined three
      subgroups responding differently to the anticancer drugs tested. In addition,
      gene expression profiling yielded distinct signatures that segregated the
      differently responding subgroups. These genes signatures involved various
      pathways, most prominently the fibroblast growth factor pathway.Conclusions: Our
      primary mesothelioma culture system has proved to be suitable to test novel
      drugs. Chemical profiling of primary mesothelioma cultures allows personalizing
      treatment for a group of patients with a rare tumor type where clinical trials
      are notoriously difficult. This personalized treatment strategy is expected to
      improve the poor prospects of patients with mesothelioma. Clin Cancer Res; 24(7);
      1761-70. (c)2017 AACRSee related commentary by John and Chia, p. 1513.

PMID- 29066507
TI  - PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in
      Lymphomas as a Single Agent and in Combination Therapy.
AB  - Purpose: Activation of the PI3K/mTOR signaling pathway is recurrent in different
      lymphoma types, and pharmacologic inhibition of the PI3K/mTOR pathway has shown
      activity in lymphoma patients. Here, we extensively characterized the in vitro
      and in vivo activity and the mechanism of action of PQR309 (bimiralisib), a novel
      oral selective dual PI3K/mTOR inhibitor under clinical evaluation, in preclinical
      lymphoma models.Experimental Design: This study included preclinical in vitro
      activity screening on a large panel of cell lines, both as single agent and in
      combination, validation experiments on in vivo models and primary cells,
      proteomics and gene-expression profiling, and comparison with other signaling
      inhibitors.Results: PQR309 had in vitro antilymphoma activity as single agent and
      in combination with venetoclax, panobinostat, ibrutinib, lenalidomide, ARV-825,
      marizomib, and rituximab. Sensitivity to PQR309 was associated with specific
      baseline gene-expression features, such as high expression of transcripts coding
      for the BCR pathway. Combining proteomics and RNA profiling, we identified the
      different contribution of PQR309-induced protein phosphorylation and gene
      expression changes to the drug mechanism of action. Gene-expression signatures
      induced by PQR309 and by other signaling inhibitors largely overlapped. PQR309
      showed activity in cells with primary or secondary resistance to
      idelalisib.Conclusions: On the basis of these results, PQR309 appeared as a novel
      and promising compound that is worth developing in the lymphoma setting. Clin
      Cancer Res; 24(1); 120-9. (c)2017 AACR.

PMID- 29066508
TI  - Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict
      Chemotherapy Treatment Outcome.
AB  - Purpose: Previous genomic studies have identified two mutually exclusive
      molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the RB1
      mutated (mostly comutated with TP53) and the RB1 wild-type groups. We assessed
      whether these subtypes have a predictive value on chemotherapy
      outcome.Experimental Design: Clinical data and tumor specimens were
      retrospectively obtained from the Netherlands Cancer Registry and Pathology
      Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in
      148 of 232 cases. Next-generation sequencing (NGS) for TP53, RB1, STK11, and
      KEAP1 genes, as well as IHC for RB1 and P16 was performed on 79 and 109 cases,
      respectively, and correlated with overall survival (OS) and progression-free
      survival (PFS), stratifying for non-small cell lung cancer type chemotherapy
      including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) and platinum
      etoposide (SCLC-PE).Results:RB1 mutation and protein loss were detected in 47% (n
      = 37) and 72% (n = 78) of the cases, respectively. Patients with RB1 wild-type
      LCNEC treated with NSCLC-GEM/TAX had a significantly longer OS [9.6; 95%
      confidence interval (CI), 7.7-11.6 months] than those treated with SCLC-PE [5.8
      (5.5-6.1); P = 0.026]. Similar results were obtained for patients expressing RB1
      in their tumors (P = 0.001). RB1 staining or P16 loss showed similar results. The
      same outcome for chemotherapy treatment was observed in LCNEC tumors harboring an
      RB1 mutation or lost RB1 protein.Conclusions: Patients with LCNEC tumors that
      carry a wild-type RB1 gene or express the RB1 protein do better with NSCLC
      GEM/TAX treatment than with SCLC-PE chemotherapy. However, no difference was
      observed for RB1 mutated or with lost protein expression. Clin Cancer Res; 24(1);
      33-42. (c)2017 AACR.

PMID- 29066509
TI  - Tumor Microvessel Density as a Prognostic Marker in High-Risk Renal Cell
      Carcinoma Patients Treated on ECOG-ACRIN E2805.
AB  - Purpose: Increased vascularity is a hallmark of renal cell carcinoma (RCC).
      Microvessel density (MVD) is one measurement of tumor angiogenesis; however, its
      utility as a biomarker of outcome is unknown. ECOG-ACRIN 2805 (E2805) enrolled
      1,943 resected high-risk RCC patients randomized to adjuvant sunitinib,
      sorafenib, or placebo. We aimed to determine the prognostic and predictive role
      of MVD in RCC.Experimental Design: We obtained pretreatment primary RCC
      nephrectomy tissues from 822 patients on E2805 and constructed tissue
      microarrays. Using quantitative immunofluorescence, we measured tumor MVD as the
      area of CD34-expressing cells. We determined the association with disease-free
      survival (DFS), overall survival (OS), treatment arm, and clinicopathologic
      variables.Results: High MVD (above the median) was associated with prolonged OS
      for the entire cohort (P = 0.021) and for patients treated with placebo (P =
      0.028). The association between high MVD and OS was weaker in patients treated
      with sunitinib or sorafenib (P = 0.060). MVD was not associated with DFS (P =
      1.00). On multivariable analysis, MVD remained independently associated with
      improved OS (P = 0.013). High MVD correlated with Fuhrman grade 1-2 (P < 0.001),
      clear cell histology (P < 0.001), and absence of necrosis (P < 0.001) but not
      with gender, age, sarcomatoid features, lymphovascular invasion, or tumor
      size.Conclusions: High MVD in resected high-risk RCC patients is an independent
      prognostic, rather than predictive, biomarker of improved OS. Further studies
      should assess whether incorporating MVD into clinical models will enhance our
      ability to predict outcome and if low MVD can be used for selection of high-risk
      patients for adjuvant therapy trials. Clin Cancer Res; 24(1); 217-23. (c)2017
      AACR.

PMID- 29066511
TI  - A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow.
AB  - Breast and prostate cancer cells home to the bone marrow, where they presumably
      hijack the hematopoietic stem cell niche. We characterize here the elusive
      premetastatic niche by examining the role of mesenchymal stromal cells (MSC) in
      cancer cell homing. Decreasing the number of MSC pharmacologically enhanced
      cancer cell homing to the bone marrow in mice. In contrast, increasing the number
      of these MSCs by various interventions including G-CSF administration diminished
      cancer cell homing. The MSC subpopulation that correlated best with cancer cells
      expressed stem, endothelial, and pericytic cell markers, suggesting these cells
      represent an undifferentiated component of the niche with vascular commitment. In
      humans, a MSC subpopulation carrying markers for endothelial and pericytic cells
      was lower in the presence of cytokeratin+ cells in bone marrow. Taken together,
      our data show that a subpopulation of MSC with both endothelial and pericytic
      cell surface markers suppresses the homing of cancer cells to the bone marrow.
      Similar to the presence of cytokeratin+ cells in the bone marrow, this MSC
      subpopulation could prove useful in determining the risk of metastatic disease,
      and its manipulation might offer a new possibility for diminishing bone
      metastasis formation.Significance: These findings establish an inverse
      relationship between a subpopulation of mesenchymal stromal cells and cancer
      cells in the bone marrow. Cancer Res; 78(1); 129-42. (c)2017 AACR.

PMID- 29066510
TI  - Evidence for Kaposi Sarcoma Originating from Mesenchymal Stem Cell through KSHV
      induced Mesenchymal-to-Endothelial Transition.
AB  - The major transmission route for Kaposi sarcoma-associated herpesvirus (KSHV)
      infection is the oral cavity through saliva. Kaposi sarcoma (KS) frequently
      occurs in the oral cavity in HIV-positive individuals and is often the first
      presenting sign of AIDS. However, the oral target cells for KSHV infection and
      the cellular origin of Kaposi sarcoma remain unknown. Here we present clinical
      and experimental evidences that Kaposi sarcoma spindle cells may originate from
      virally modified oral mesenchymal stem cells (MSC). AIDS-KS spindle cells
      expressed neuroectodermal stem cell marker (Nestin) and oral MSC marker CD29,
      suggesting an oral/craniofacial MSC lineage of AIDS-associated Kaposi sarcoma.
      Furthermore, oral MSCs were highly susceptible to KSHV infection, and infection
      promoted multilineage differentiation and mesenchymal-to-endothelial transition
      (MEndT). KSHV infection of oral MSCs resulted in expression of a large number of
      cytokines, a characteristic of Kaposi sarcoma, and upregulation of Kaposi sarcoma
      signature and MEndT-associated genes. These results suggest that Kaposi sarcoma
      may originate from pluripotent MSC and KSHV infection transforms MSC to Kaposi
      sarcoma-like cells through MEndT.Significance: These findings indicate that
      Kaposi sarcomas, which arise frequently in AIDS patients, originate from neural
      crest-derived mesenchymal stem cells, with possible implications for improving
      the clnical treatment of this malignancy. Cancer Res; 78(1); 230-45. (c)2017
      AACR.

PMID- 29066512
TI  - CBX8 Exhibits Oncogenic Activity via AKT/beta-Catenin Activation in
      Hepatocellular Carcinoma.
AB  - Deregulation of polycomb proteins influences the development and progression of
      hepatocellular carcinoma. Here we show that chromobox 8 (CBX8) expression is
      increased in hepatocellular carcinoma and correlates with poor outcome in two
      independent cohorts containing a total of 879 cases. Ectopic expression of CBX8
      facilitated tumor growth and metastasis, whereas CBX8 silencing suppressed these
      effects. CBX8 efficiently activated AKT/beta-catenin signaling via upregulation
      of the transcription factor EGR1 and miR-365-3p in a noncanonical manner: CBX8
      directly bound the EGR1 promoter to enhance its activity. In the nucleus, CBX8
      also interacted with EGR1 to prevent its degradation. Furthermore, CBX8 increased
      the transcription of miR-365a-3p, which promoted the nuclear localization of beta
      catenin by targeting the 3'-UTR ZNRF1. Inhibiting either EGR1 or miR-365a-3p
      partially rescued CBX8-mediated malignant phenotypes. In clinical samples, CBX8
      expression closely correlated with EGR1, miR-365a-3p, and nuclear beta-catenin.
      Collectively, our results show that CBX8 functions as an oncogene to upregulate
      EGR1 and miR-365-3p to stimulate the AKT/beta-catenin pathway. This newly
      identified signaling axis may suggest new therapeutic strategies against
      hepatocellular carcinoma.Significance: Elucidation of a key new element of the
      beta-catenin signaling pathway in liver cancer may suggest new therapeutic
      targets. Cancer Res; 78(1); 51-63. (c)2017 AACR.

PMID- 29066513
TI  - Comparative Transcriptome Analysis Quantifies Immune Cell Transcript Levels,
      Metastatic Progression, and Survival in Osteosarcoma.
AB  - Overall survival of patients with osteosarcoma (OS) has improved little in the
      past three decades, and better models for study are needed. OS is common in large
      dog breeds and is genetically inducible in mice, making the disease ideal for
      comparative genomic analyses across species. Understanding the level of
      conservation of intertumor transcriptional variation across species and how it is
      associated with progression to metastasis will enable us to more efficiently
      develop effective strategies to manage OS and to improve therapy. In this study,
      transcriptional profiles of OS tumors and cell lines derived from humans (n =
      49), mice (n = 103), and dogs (n = 34) were generated using RNA sequencing.
      Conserved intertumor transcriptional variation was present in tumor sets from all
      three species and comprised gene clusters associated with cell cycle and mitosis
      and with the presence or absence of immune cells. Further, we developed a novel
      gene cluster expression summary score (GCESS) to quantify intertumor
      transcriptional variation and demonstrated that these GCESS values associated
      with patient outcome. Human OS tumors with GCESS values suggesting decreased
      immune cell presence were associated with metastasis and poor survival. We
      validated these results in an independent human OS tumor cohort and in 15
      different tumor data sets obtained from The Cancer Genome Atlas. Our results
      suggest that quantification of immune cell absence and tumor cell proliferation
      may better inform therapeutic decisions and improve overall survival for OS
      patients.Significance: This study offers new tools to quantify tumor
      heterogeneity in osteosarcoma, identifying potentially useful prognostic
      biomarkers for metastatic progression and survival in patients. Cancer Res;
      78(2); 326-37. (c)2017 AACR.

PMID- 29066514
TI  - CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells.
AB  - The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability
      to engender an immunosuppressive microenvironment. Here we describe a subset of
      tumor-infiltrating CD8+ T cells marked by high expression of the
      immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T
      cells increased with tumor growth but was absent in lymphoid organs. Tumor
      infiltrating CD8+ T cells with high CD39 expression exhibited features of
      exhaustion, such as reduced production of TNF and IL2 and expression of
      coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed
      extracellular ATP, confirming that CD39 is enzymatically active. Furthermore,
      exhausted CD39+CD8+ T cells inhibited IFNgamma production by responder CD8+ T
      cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells
      were present within tumors and invaded or metastatic lymph nodes, but were barely
      detectable within noninvaded lymph nodes and absent in peripheral blood. These
      cells exhibited an exhausted phenotype with impaired production of IFNgamma, TNF,
      IL2, and high expression of coinhibitory receptors. Although T-cell receptor
      engagement was sufficient to induce CD39 on human CD8+ T cells, exposure to IL6
      and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine
      sources. Our findings show how the tumor microenvironment drives the acquisition
      of CD39 as an immune regulatory molecule on CD8+ T cells, with implications for
      defining a biomarker of T-cell dysfunction and a target for immunotherapeutic
      intervention.Significance: The tumor microenvironment elicits a subset of
      functionally exhausted CD8+ T cells by creating conditions that induce cell
      surface expression of CD39, an immunosuppressive molecule that can be
      therapeutically targeted to restore effector T-cell function. Cancer Res; 78(1);
      115-28. (c)2017 AACR.

PMID- 29066515
TI  - Cross-Cancer Analysis Reveals Novel Pleiotropic Associations-Response.

PMID- 29066517
TI  - Sleep and REM sleep behaviour disorder in Parkinson's disease with impulse
      control disorder.
AB  - INTRODUCTION: Because the association between rapid eye movement sleep behaviour
      disorder (RBD) and impulse control disorders (ICDs) in Parkinson's disease (PD)
      has been debated, we assessed the sleep characteristics and the frequency of RBD
      using video-polysomnography (v-PSG) in patients with PD with versus without ICDs.
      METHODS: Eighty non-demented patients with PD consecutively identified during
      routine evaluation at three movement disorders centres were enrolled in a case
      control study. Forty patients (22 men; mean age: 62.6+/-9.7 years, Hoehn & Yahr:
      2.1+/-0.6) with one or more current ICDs were age-matched and sex-matched with 40
      patients with no history of ICDs (22 men, mean age: 64.9+/-7.8 years, Hoehn &
      Yahr: 2.2+/-0.6). They underwent a detailed sleep interview followed by a full
      night in-lab v-PSG. Sleep was scored blindly to ICDs condition and RBD diagnosis
      included a clinical complaint of enacted dreams and/or documented behaviour
      during rapid eye movement (REM) sleep, with the presence of quantified REM sleep
      without atonia (RSWA). RESULTS: Patients with ICDs had a higher arousal index and
      higher RSWA than those without ICDs (51.9%+/-28.2%vs 32.2+/-27.1%, p=0.004). In
      addition, RBD was more frequent in the ICD group (85%vs53%, p=0.0001). RBD was
      still associated with ICDs in a multivariate regression analysis including age of
      onset, PD duration and severity, treatment duration, levodopa-equivalent and
      dopamine agonist-equivalent daily doses and antidepressant use (OR: 4.9 (95% CI
      1.3 to 18.5), p=0.02). CONCLUSIONS: This large, controlled series of patients
      with PD with ICDs assessed by v-PSG confirms the association between ICDs and
      RBD. Increased surveillance of symptoms of ICDs should be recommended in patients
      with PD with RBD.

PMID- 29066518
TI  - Apathy: a neurocircuitry model based on frontotemporal dementia.
AB  - Apathy is a symptom shared among many neurological and psychiatric disorders.
      However, the underlying neurocircuitry remains incompletely understood. Apathy is
      one of the core features of behavioural variant frontotemporal dementia (bvFTD),
      a neurodegenerative disease presenting with heterogeneous combinations of
      socioaffective symptoms and executive dysfunction. We reviewed all neuroimaging
      studies of apathy in frontotemporal dementia (FTD) attempting to refine a
      neurocircuitry model and inform clinical definitions. Levels of apathy have been
      consistently shown to correlate with the severity of executive dysfunctions
      across a wide range of diseases, including FTD. Some authors view 'energisation'
      the loss of which is central in apathy-as a core executive function. Apathy in
      FTD is most robustly associated with atrophy, hypometabolism and/or hypoperfusion
      in the dorsolateral prefrontal cortex, the anterior and middle cingulate cortex,
      the orbitofrontal cortex and the medial and ventromedial superior frontal gyri.
      Data also suggest that abnormalities in connecting white matter pathways and
      functionally connected more posterior cortical areas could contribute to apathy.
      There is a lack of consistency across studies due to small samples, lenient
      statistical thresholds, variable measurement scales and the focus on apathy as a
      unitary concept. Integrating findings across studies, we revise a neurocircuitry
      model of apathy divided along three subcomponents (cognition/planning,
      initiation, emotional-affective/motivation) with specific neuroanatomical and
      cognitive substrates. To increase consistency in clinical practice, a
      recommendation is made to modify the bvFTD diagnostic criteria of apathy/inertia.
      More generally, we argue that bvFTD constitutes a disease model to study the
      neurocircuitry of complex behaviours as a 'lesion-based' approach to
      neuropsychiatric symptoms observed across diagnostic categories.

PMID- 29066516
TI  - Cross-Cancer Analysis Reveals Novel Pleiotropic Associations-Letter.

PMID- 29066519
TI  - It's not always that simplex.

PMID- 29066520
TI  - What dose of aspirin should be used in the initial treatment of Kawasaki disease?

PMID- 29066521
TI  - Bone protective agents in children.
AB  - Evaluation of bone health in childhood is important to identify children who have
      inadequate bone mineralisation and who may benefit from interventions to decrease
      their risk of osteoporosis and subsequent fracture. There are no bone protective
      agents that are licensed specifically for the prevention and treatment of
      osteoporosis in children. In this review, we discuss the mechanism of action and
      use of bisphosphonates and other new and established bone protective agents in
      children.

PMID- 29066522
TI  - Development and progress of the National Congenital Anomaly and Rare Disease
      Registration Service.

PMID- 29066523
TI  - Non-operative management of appendicitis in children.
AB  - While appendicectomy has been considered the mainstay of treatment for children
      with acute appendicitis for many decades, there has been a great deal of recent
      interest in non-operative treatment (NOT) with antibiotics alone. Initial results
      suggest that many children with appendicitis can indeed be safely treated with
      NOT and can be spared the surgeon's knife. Many as yet unanswered questions
      remain, however, before NOT can be considered a realistic and reliable
      alternative to surgery. This review summaries current knowledge and understanding
      of the role of NOT in children with appendicitis and outlines and discusses the
      outstanding knowledge gaps.

PMID- 29066524
TI  - Identification of health risk behaviours among adolescent refugees resettling in
      Western Australia.
AB  - OBJECTIVE: Adolescent refugees encounter traumatic stressors and are at risk of
      developing psychosocial health problems; limited research data exist
      internationally. This study aims to identify health risk behaviours among
      adolescent refugees resettling in Western Australia and assess the feasibility of
      using a standardised adolescent health questionnaire for this purpose. DESIGN:
      Refugees aged 12 years and above attending a tertiary Refugee Health Service
      (RHS) were recruited over 12 months. Sociodemographic data were collected.
      Psychosocial assessments based on the 'Home, Education/Eating, Activities, Drugs,
      Sexuality, Suicide/mental health' (HEADSS) framework were undertaken utilising
      interpreters where required. Health concerns identified were managed through the
      RHS. RESULTS: A total of 122 adolescents (20 ethnicities) participated; 65%
      required interpreters. Median age (range) was 14 (12-17) years. Most (80%) had
      nuclear family separation. Almost half (49%) had a deceased/missing family
      member. A third (37%) had lived in refugee camps and 20% had experienced closed
      detention. The median time (range) since arrival in Australia was 11 (2-86)
      months. Every adolescent had at least one health concern identified during the
      psychosocial assessment. Frequency of health concerns identified in each domain
      were 87% for home, 66% for education, 23% for eating, 93% for activities, 5% for
      drugs, 88% for sexuality and 61% for suicide/mental health. Most adolescents
      (75%) required intervention, consisting of counselling for health risk behaviours
      and/or referral to health or community services. CONCLUSION: It is feasible to
      use a standardised adolescent health questionnaire to identify health risk
      behaviours among a cohort of ethnically diverse adolescent refugees. Use of the
      questionnaire identified a large burden of psychosocial health issues requiring
      multidisciplinary intervention.

PMID- 29066525
TI  - Question 2: Are three malaria tests necessary in children returning from the
      tropics with fever?

PMID- 29066526
TI  - Are neutrophils the culprit in CF lung damage?

PMID- 29066527
TI  - The endoplasmic reticulum, calcium signaling and junction turnover in Sertoli
      cells.
AB  - The endoplasmic reticulum (ER) forms a continuous network throughout
      morphologically differentiated Sertoli cells. It is an integral component of
      intercellular adhesion junctions in this cell type, as well as forming membrane
      contact sites with the plasma membrane and intracellular organelles. One of the
      major functions of the ER in cells generally is maintaining calcium homeostasis
      and generating calcium signals. In this review, we discuss what is currently
      known about the overall pattern of distribution of the ER in Sertoli cells and
      the location of calcium regulatory machinery in the various subdomains of the
      organelle. Current data are consistent with the hypothesis that calcium signaling
      by the ER of Sertoli cells may play a significant role in events related to
      junction remodeling that occur in the seminiferous epithelium during
      spermatogenesis.

PMID- 29066528
TI  - Acute nutrient treatment causes alterations in intra-follicular antioxidation and
      AKT signaling.
AB  - This study aimed to determine if short-term nutrient alteration affects (1)
      ovarian morphology, (2) plasma and ovarian antioxidant capability and (3) cell
      apoptosis and AKT signaling within the ovary. After estrus synchronization, 24 Hu
      sheep were assigned to three groups based on the nutrient requirement recommended
      for maintenance (M): 1 * M (Control), 1.5 * M (S) and 0.5 * M (R) during days 7
      14 of their estrous cycle. The results indicated that undernourishment
      significantly increased the counts and volume of follicles <2.5 mm and decreased
      the counts and volume of follicles >=2.5 mm (P < 0.05). Feed restriction altered
      the plasma and follicular redox balance within follicles >=2.5 mm by inhibiting
      total antioxidant capacity, increasing malondialdehyde concentration (P < 0.05)
      and reducing the mRNA expression levels of superoxide dismutase 2 (SOD2) and
      glutathione peroxidase (GSH-PX), as well as the activities of total SOD and GSH
      PX. Feed restriction also attenuated B-cell lymphoma-2 (BCL2) but enhanced Bcl-2
      associated X protein (BAX) and BAX/BCL2 transcription and translation levels in
      granulosa cells (P < 0.05). Uniform staining intensities of AKT and P-AKT-Ser473
      were observed in each follicle stage, whereas weaker P-AKT-Thr308 staining in the
      antral follicle than in the pre-antral follicle suggested possible involvement of
      P-AKT-Thr308 during the beginning of follicle development. P-AKT-Ser473 levels in
      follicles >=2.5 mm was significantly reduced in the R group (P < 0.05). The
      results presented in this study demonstrate that suppressed folliculogenesis
      caused by feed restriction might be associated with attenuated AKT signaling,
      reduced follicular antioxidant capacity and enhanced granulosa cells apoptosis.

PMID- 29066529
TI  - Steroidogenic enzyme activities in the pre- and post-parturient equine placenta.
AB  - Steroidogenic enzymes in placentas shape steroid hormone profiles in the maternal
      circulation of each mammalian species. These include 3beta-hydroxysteroid
      dehydrogenase/Delta5-4 isomerase (3betaHSD) and 17alpha-hydroxylase/17,20-lyase
      cytochrome P450 (P450c17) crucial for progesterone and androgen synthesis,
      respectively, as well as aromatase cytochrome P450 (P450arom) that converts
      Delta4-androgens to estrogens. 5alpha-reductase is another important enzyme in
      equine placentas because 5alpha-dihydroprogesterone (DHP) sustains pregnancy in
      the absence of progesterone in the second half of equine pregnancy. DHP and its
      metabolites decline dramatically days before foaling, but few studies have
      investigated placental enzyme activity before or at parturition in mares. Thus,
      key enzyme activities and transcript abundance were investigated in equine
      placentas at 300 days of gestation (GD300) and post-partum (term). Equine testis
      was used as a positive control for P450c17 activity. Substrates were incubated
      with microsomal preparations, together with enzyme inhibitors, and products were
      measured by liquid chromatography tandem mass spectrometry or radiometric methods
      (aromatase). Equine placenta expressed high levels of 3betaHSD, 5alpha-reductase
      and aromatase, and minimal P450c17 activity at GD300 compared with testis (600
      fold higher). At foaling, 3betaHSD and aromatase activities and transcript
      abundance were unchanged but 5alpha-reductase (and P450c17) was no longer
      detectable (P < 0.05) and transcript was decreased. Trilostane inhibited 3betaHSD
      significantly more in testis than placenta, suggesting possible existence of
      different 3betaHSD isoforms. Equine placentas have significant capacity for
      steroid metabolism by 5alpha-reductase, 3betaHSD and aromatase but little for
      androgen synthesis lacking P450c17. Declining pre-partum 5alpha-reduced pregnane
      concentrations coincide with selective loss of placental 5alpha-reductase
      activity and expression at parturition in horses.

PMID- 29066530
TI  - Regulation of porcupine-dependent Wnt signaling is essential for uterine
      development and function.
AB  - Six members of the Wnt family are expressed in the female reproductive tract.
      Their collective function ensures proper development of the uterus, preparing it
      for pregnancy during adulthood. Here, we take advantage of the fact that Porcn, a
      prerequisite for all Wnt secretion, is located on the X chromosome, to generate
      females that were mosaic for Porcn throughout the reproductive tract. Porcnflox/+
      females were mated with progesterone receptor (Pgr)-Cre males (PgrCre/+ ) to
      generate females that were heterozygous for Porcupine in all tissues of the
      female reproductive tract, resulting in mosaicism due to random X-inactivation.
      We demonstrated that Porcn mosaic females are extremely subfertile and exhibit a
      large spectrum of phenotypes ranging from morphologically normal uteri to uteri
      with extremely enlarged cystic glands. Decreased fertility in Porcupine mosaic
      females was not associated with phenotype severity and was observed regardless of
      whether or not cystic glands were enlarged. By crossing-in a GFP reporter on the
      wild-type X chromosome, we were able to correlate endometrial gland hyperplasia
      with a mostly Porcupine mutant stroma, demonstrating the role of stromal Wnts in
      the regulation of endometrial gland proliferation. Finally, we demonstrated that
      fertility issues within mosaic females were due to a reduced response to estrogen
      and to abnormal Tcf/Lef signaling across the mesometrial-anti-mesometrial axis
      during the window of implantation.

PMID- 29066532
TI  - Impact of the PROFHER trial findings on surgeons' clinical practice: An online
      questionnaire survey.
AB  - OBJECTIVES: To explore whether orthopaedic surgeons have adopted the Proximal
      Fracture of the Humerus: Evaluation by Randomisation (PROFHER) trial results
      routinely into clinical practice. METHODS: A questionnaire was piloted with six
      orthopaedic surgeons using a 'think aloud' process. The final questionnaire
      contained 29 items and was distributed online to surgeon members of the British
      Orthopaedic Association and British Elbow and Shoulder Society. Descriptive
      statistics summarised the sample characteristics and fracture treatment of
      respondents overall, and grouped them by whether they changed practice based on
      PROFHER trial findings. Free-text responses were analysed qualitatively for
      emerging themes using Framework Analysis principles. RESULTS: There were complete
      responses from 265 orthopaedic and trauma surgeons who treat patients with
      proximal humeral fractures. Around half (137) had changed practice to various
      extents because of PROFHER, by operating on fewer PROFHER-eligible fractures. A
      third (43) of the 128 respondents who had not changed practice were already
      managing patients non-operatively. Those who changed practice were more likely to
      be younger, work in a trauma unit rather than a major trauma centre, be
      specialist shoulder surgeons and treat fewer PROFHER-eligible fractures
      surgically. This group gave higher scores when assessing validity and
      applicability of PROFHER. In contrast, a quarter of the non-changers were
      critical, sometimes emphatically, of PROFHER. The strongest theme that emerged
      overall was the endorsement of evidence-based practice. CONCLUSION: PROFHER has
      had an impact on surgeons' clinical practice, both through changing it, and
      through underpinning existing non-operative practice. Although some respondents
      expressed reservations about the trial, evidence from such trials was found to be
      the most important influence on surgeons' decisions to change practice.Cite this
      article: L. Jefferson, S. Brealey, H. Handoll, A. Keding, L. Kottam, I. Sbizzera,
      A. Rangan. Impact of the PROFHER trial findings on surgeons' clinical practice:
      An online questionnaire survey. Bone Joint Res 2017;6:590-599. DOI: 10.1302/2046
      3758.610.BJR-2017-0170.

PMID- 29066533
TI  - The reporting of outcomes in randomised controlled trials: The switch and the
      spin.

PMID- 29066531
TI  - Extracellular matrix (ECM) activates beta-catenin signaling in uterine fibroids.
AB  - Recent studies showed that genetic aberrations in the MED12 gene, probably
      through the canonical WNT/beta-catenin pathway, lead to the pathogenesis of
      uterine fibroids. However, a comprehensive analysis of the WNT pathway in MED12
      mutated and MED12-wild-type fibroids has not been performed. The objective of
      this study was to determine the status of the WNT pathway in human fibroids. We
      performed Sanger sequencing to define the MED12 mutational status of fibroids and
      normal myometrium samples. qPCR arrays were carried out to determine the status
      of the WNT signaling pathway in MED12-mutated and MED12-wild-type fibroids.
      Liquid chromatography-mass spectrometry (LC-MS), Western blotting and
      immunohistochemistry were used to monitor the expression of beta-catenin. We
      showed that beta-catenin expression was increased in fibroids compared to the
      adjacent myometrium samples. However, beta-catenin expression showed no
      correlation with MED12 mutation status. Of all the WNT signaling components, WNT
      inhibitors showed the greatest differences in expression between fibroids and
      controls. WIF1, a WNT inhibitor, was identified as the most significantly
      upregulated gene in fibroids. We cultured primary fibroid cells on hydrogels of
      known stiffness to decipher the influence of biomechanical cues on beta-catenin
      expression and revealed increased levels of beta-catenin when cells were cultured
      on a stiffer surface. In conclusion, our data showed that beta-catenin expression
      in fibroids occurs independently of MED12 mutations. Biomechanical changes
      upregulate beta-catenin expression in fibroids, providing an attractive avenue
      for developing new treatments for this disease.

PMID- 29066535
TI  - Obinutuzumab Effective in Follicular Lymphoma, but at a Cost.
AB  - In a phase III trial involving more than 1,200 patients with follicular lymphoma,
      obinutuzumab plus chemotherapy reduced the risk of disease progression, relapse,
      or death by 34% compared with rituximab plus chemotherapy. However, patients
      receiving obinutuzumab experienced more serious side effects than those receiving
      rituximab.

PMID- 29066534
TI  - The effect of long-term bisphosphonate therapy on trabecular bone strength and
      microcrack density.
AB  - OBJECTIVES: Bisphosphonates (BP) are the first-line treatment for preventing
      fragility fractures. However, concern regarding their efficacy is growing because
      bisphosphonate is associated with over-suppression of remodelling and
      accumulation of microcracks. While dual-energy X-ray absorptiometry (DXA)
      scanning may show a gain in bone density, the impact of this class of drug on
      mechanical properties remains unclear. We therefore sought to quantify the
      mechanical strength of bone treated with BP (oral alendronate), and correlate
      data with the microarchitecture and density of microcracks in comparison with
      untreated controls. METHODS: Trabecular bone from hip fracture patients treated
      with BP (n = 10) was compared with naive fractured (n = 14) and non-fractured
      controls (n = 6). Trabecular cores were synchrotron scanned and micro-CT scanned
      for microstructural analysis, including quantification of bone volume fraction,
      microarchitecture and microcracks. The specimens were then mechanically tested in
      compression. RESULTS: BP bone was 28% lower in strength than untreated hip
      fracture bone, and 48% lower in strength than non-fractured control bone (4.6 MPa
      vs 6.4 MPa vs 8.9 MPa). BP-treated bone had 24% more microcracks than naive
      fractured bone and 51% more than non-fractured control (8.12/cm2vs 6.55/cm2vs
      5.25/cm2). BP and naive fracture bone exhibited similar trabecular
      microarchitecture, with significantly lower bone volume fraction and connectivity
      than non-fractured controls. CONCLUSION: BP therapy had no detectable mechanical
      benefit in the specimens examined. Instead, its use was associated with
      substantially reduced bone strength. This low strength may be due to the greater
      accumulation of microcracks and a lack of any discernible improvement in bone
      volume or microarchitecture. This preliminary study suggests that the clinical
      impact of BP-induced microcrack accumulation may be significant.Cite this
      article: A. Jin, J. Cobb, U. Hansen, R. Bhattacharya, C. Reinhard, N. Vo, R.
      Atwood, J. Li, A. Karunaratne, C. Wiles, R. Abel. The effect of long-term
      bisphosphonate therapy on trabecular bone strength and microcrack density. Bone
      Joint Res 2017;6:602-609. DOI: 10.1302/2046-3758.610.BJR-2016-0321.R1.

PMID- 29066536
TI  - Making Bryostatin 1 through Smart Chemistry.
AB  - Scientists have come up with an efficient, scalable way to chemically synthesize
      bryostatin 1, a marine-derived natural PKC modulator that has been in scarce
      supply, impeding a thorough evaluation of its therapeutic potential.

PMID- 29066537
TI  - How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome.
AB  - Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a
      genetic disease characterized by neutropenia, lymphopenia, susceptibility to
      infections, and myelokathexis, which describes degenerative changes of mature
      neutrophils and hyperplasia of bone marrow myeloid cells. Some patients present
      with hypogammaglobulinemia and/or refractory warts of skin and genitalia.
      Congenital cardiac defects constitute uncommon manifestations of the disease. The
      disorder, which is inherited as an autosomal dominant trait, is caused by
      heterozygous mutations of the chemokine receptor CXCR4. These mutations lead to
      an increased sensitivity of neutrophils and lymphocytes to the unique ligand
      CXCL12 and to an increased accumulation of mature neutrophils in the bone marrow.
      Despite greatly improved knowledge of the disease, therapeutic choices are
      insufficient to prevent some of the disease outcomes, such as development of
      bronchiectasis, anogenital dysplasia, or invasive cancer. The available
      therapeutic measures aimed at preventing the risk for infection in WHIM patients
      are discussed. We critically evaluate the diagnostic criteria of WHIM syndrome,
      particularly when WHIM syndrome should be suspected in patients with congenital
      neutropenia and lymphopenia despite the absence of hypogammaglobulinemia and/or
      warts. Finally, we discuss recent results of trials evaluating plerixafor, a
      selective antagonist of CXCR4, as a mechanism-oriented strategy for treatment of
      WHIM patients.

PMID- 29066538
TI  - The scaffolding protein Cnk binds to the receptor tyrosine kinase Alk to promote
      visceral founder cell specification in Drosophila.
AB  - In Drosophila melanogaster, the receptor tyrosine kinase (RTK) anaplastic
      lymphoma kinase (Alk) and its ligand jelly belly (Jeb) are required to specify
      muscle founder cells in the visceral mesoderm. We identified a critical role for
      the scaffolding protein Cnk (connector enhancer of kinase suppressor of Ras) in
      this signaling pathway. Embryos that ectopically expressed the minimal Alk
      interaction region in the carboxyl terminus of Cnk or lacked maternal and zygotic
      cnk did not generate visceral founder cells or a functional gut musculature,
      phenotypes that resemble those of jeb and Alk mutants. Deletion of the entire Alk
      interacting region in the cnk locus affected the Alk signaling pathway in the
      visceral mesoderm and not other RTK signaling pathways in other tissues. In
      addition, the Cnk-interacting protein Aveugle (Ave) was critical for Alk
      signaling in the developing visceral mesoderm. Alk signaling stimulates the
      MAPK/ERK pathway, but the scaffolding protein Ksr, which facilitates activation
      of this pathway, was not required to promote visceral founder cell specification.
      Thus, Cnk and Ave represent critical molecules downstream of Alk, and their loss
      genocopies the lack of visceral founder cell specification of Alk and jeb
      mutants, indicating their essential roles in Alk signaling.

PMID- 29066539
TI  - TCR-stimulated changes in cell surface CD46 expression generate type 1 regulatory
      T cells.
AB  - A lack of regulatory T cell function is a critical factor in the pathogenesis of
      autoimmune diseases, such as multiple sclerosis (MS). Ligation of the complement
      regulatory protein CD46 facilitates the differentiation of T helper 1 (TH1)
      effector cells into interleukin-10 (IL-10)-secreting type 1 regulatory T cells
      (Tr1 cells), and this pathway is defective in MS patients. Cleavage of the
      ectodomain of CD46, which contains three N-glycosylation sites and multiple O
      glycosylation sites, enables CD46 to activate T cells. We found that stimulation
      of the T cell receptor (TCR)-CD3 complex was associated with a reduction in the
      apparent molecular mass of CD46 in a manner that depended on O-glycosylation. CD3
      stimulated changes in CD46 O-glycosylation status reduced CD46 processing and
      subsequent T cell signaling. During T cell activation, CD46 was recruited to the
      immune synapse in a manner that required its serine-, threonine-, and proline
      rich (STP) region, which is rich in O-glycosylation sites. Recruitment of CD46 to
      the immune synapse switched T cells from producing the inflammatory cytokine
      interferon-gamma (IFN-gamma) to producing IL-10. Furthermore, CD4+ T cells
      isolated from MS patients did not exhibit a CD3-stimulated reduction in the mass
      of CD46 and thus showed increased amounts of cell surface CD46. Together, these
      data suggest a possible mechanism underlying the regulatory function of CD46 on T
      cells. Our findings may explain why this pathway is defective in patients with MS
      and provide insights into MS pathogenesis that could help to design future
      immunotherapies.

PMID- 29066541
TI  - Pseudomonas syringae pv. syringae B728a Regulates Multiple Stages of Plant
      Colonization via the Bacteriophytochrome BphP1.
AB  - Light may be an important environmental signal for plant-associated bacteria,
      particularly those that live on leaves. An integrated network of red/far-red- and
      blue-light-responsive photosensory proteins is known to inhibit swarming motility
      in the foliar plant pathogen Pseudomonas syringae pv. syringae B728a. Here we
      elucidated factors in the red/far-red-light-sensing bacteriophytochrome BphP1
      signal transduction pathway and report evidence for a role of BphP1 in multiple
      stages of the Psyringae B728a life cycle. We report that BphP1 signaling involves
      the downstream regulator Bsi (bacteriophytochrome-regulated swarming inhibitor)
      and an acyl-homoserine lactone (AHL) signal. Loss of bphP1 or bsi resulted in the
      early initiation of swarm tendrils during swarming motility, a phenotype that was
      dependent on red/far-red light and reversed by exogenous AHL, illustrating that
      the BphP1-Bsi-AHL pathway inhibits the transition from a sessile state to a
      motile state. Loss of bphP1 or bsi resulted in larger water-soaked lesions
      induced on bean (Phaseolus vulgaris) pods and enhanced movement from soil and
      buried plant tissues to seeds, demonstrating that BphP1 and Bsi negatively
      regulate virulence and bacterial movement through soil to seeds. Moreover, BphP1,
      but not Bsi, contributed to leaf colonization; loss of bphP1 reduced survival on
      leaves immediately following inoculation but enhanced the size of the
      subsequently established populations. Neither Bsi nor Smp, a swarm motility
      promoting regulator identified here, affected leaf colonization, indicating that
      BphP1-mediated contributions to leaf colonization are, at least in part,
      independent of swarming motility. These results demonstrate that Psyringae B728a
      red-light sensing involves a multicomponent, branched regulatory pathway that
      affects several stages of its life cycle.IMPORTANCE Microbes on plants are
      particularly well positioned to exploit light cues based on the importance of
      light to plant growth. Photosensory proteins enable organisms to sense light and
      respond to light, but their roles in the life cycles of plant microbes are poorly
      understood. This study investigated the cellular components and ecological roles
      of red/far-red-light sensing in the foliar bacterial pathogen Pseudomonas
      syringae The study demonstrated that a bacteriophytochrome photosensory protein
      functions via a multicomponent, branched regulatory pathway that operates
      primarily through red/far-red-light-mediated inhibition. This pathway negatively
      regulates the transition from sessile to motile states under conditions conducive
      to swarming motility. It also negatively regulates virulence on bean pods,
      movement through soil to seeds, and survival following inoculation on leaves, but
      it positively contributes to the eventual establishment of leaf-borne
      populations. These results provide strong evidence that light sensing modulates
      behaviors at multiple stages in the life cycle of a nonphotosynthetic, plant
      microbe.

PMID- 29066540
TI  - TGF-beta receptor I/II trafficking and signaling at primary cilia are inhibited
      by ceramide to attenuate cell migration and tumor metastasis.
AB  - Signaling by the transforming growth factor-beta (TGF-beta) receptors I and II
      (TbetaRI/II) and the primary cilia-localized sonic hedgehog (Shh) pathway promote
      cell migration and, consequently, tumor metastasis. In contrast, the sphingolipid
      ceramide inhibits cell proliferation and tumor metastasis. We investigated
      whether ceramide metabolism inhibited TbetaRI/II trafficking to primary cilia to
      attenuate cross-talk between TbetaRI/II and the Shh pathway. We found that
      ceramide synthase 4 (CerS4)-generated ceramide stabilized the association between
      TbetaRI and the inhibitory factor Smad7, which limited the trafficking of
      TbetaRI/II to primary cilia. Expression of a mutant TbetaRI that signals but does
      not interact with Smad7 prevented the CerS4-mediated inhibition of migration in
      various cancer cells. Genetic deletion or knockdown of CerS4 prevented the
      formation of the Smad7-TbetaRI inhibitory complex and increased the association
      between TbetaRI and the transporter Arl6 through a previously unknown cilia
      targeting signal (Ala31Thr32Ala33Leu34Gln35) in TbetaRI. Mutating the cilia
      targeting signal abolished the trafficking of TbetaRI to the primary cilia.
      Localization of TbetaRI to primary cilia activated a key mediator of Shh
      signaling, Smoothened (Smo), which stimulated cellular migration and invasion.
      TbetaRI-Smo cross-talk at the cilia in CerS4-deficient 4T1 mammary cancer cells
      induced liver metastasis from orthotopic allografts in both wild-type and CerS4
      deficient mice, which was prevented by overexpression of Smad7 or knockdown of
      intraflagellar transport protein 88 (IFT88). Overall, these data reveal a
      ceramide-dependent mechanism that suppresses cell migration and invasion by
      restricting TbetaRI/II-Shh signaling selectively at the plasma membrane of the
      primary cilium.

PMID- 29066543
TI  - Chronic Vaginal Candidiasis Is Achievable in Outbred CD-1 Mice.

PMID- 29066542
TI  - Mechanisms of CNS Viral Seeding by HIV+ CD14+ CD16+ Monocytes: Establishment and
      Reseeding of Viral Reservoirs Contributing to HIV-Associated Neurocognitive
      Disorders.
AB  - HIV reservoirs persist despite antiretroviral therapy (ART) and are established
      within a few days after infection. Infected myeloid cells in the central nervous
      system (CNS) may contribute to the establishment of a CNS viral reservoir. The
      mature CD14+ CD16+ monocyte subset enters the CNS in response to chemokines,
      including CCL2. Entry of infected CD14+ CD16+ monocytes may lead to infection of
      other CNS cells, including macrophages or microglia and astrocytes, and to
      release of neurotoxic early viral proteins and additional cytokines. This
      contributes to neuroinflammation and neuronal damage leading to HIV-associated
      neurocognitive disorders (HAND) in ~50% of HIV-infected individuals despite ART.
      We examined the mechanisms of monocyte entry in the context of HIV infection and
      report for the first time that HIV+ CD14+ CD16+ monocytes preferentially
      transmigrate across the blood-brain barrier (BBB). The junctional proteins JAM-A
      and ALCAM and the chemokine receptor CCR2 are essential to their preferential
      transmigration across the BBB to CCL2. We show here that JAM-A and ALCAM are
      increased on HIV+ CD14+ CD16+ monocytes compared to their expression on HIVexp
      CD14+ CD16+ monocytes-cells that are uninfected but exposed to HIV, viral
      proteins, and inflammatory mediators. Antibodies against JAM-A and ALCAM and the
      novel CCR2/CCR5 dual inhibitor cenicriviroc prevented or significantly reduced
      preferential transmigration of HIV+ CD14+ CD16+ monocytes. This indicates that
      JAM-A, ALCAM, and CCR2 may be potential therapeutic targets to block entry of
      these infected cells into the brain and prevent or reduce the establishment and
      replenishment of viral reservoirs within the CNS.IMPORTANCE HIV infects different
      tissue compartments of the body, including the central nervous system (CNS). This
      leads to establishment of viral reservoirs within the CNS that mediate
      neuroinflammation and neuronal damage, contributing to cognitive impairment. Our
      goal was to examine the mechanisms of transmigration of cells that contribute to
      HIV infection of the CNS and to continued replenishment of CNS viral reservoirs,
      to establish potential therapeutic targets. We found that an HIV-infected subset
      of monocytes, mature HIV+ CD14+ CD16+ monocytes, preferentially transmigrates
      across the blood-brain barrier. This was mediated, in part, by increased
      junctional proteins JAM-A and ALCAM and chemokine receptor CCR2. We show that the
      CCR2/CCR5 dual inhibitor cenicriviroc and blocking antibodies against the
      junctional proteins significantly reduce, and often completely block, the
      transmigration of HIV+ CD14+ CD16+ monocytes. This suggests new opportunities to
      eliminate infection and seeding or reseeding of viral reservoirs within the CNS,
      thus reducing neuroinflammation, neuronal damage, and cognitive impairment.

PMID- 29066544
TI  - Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with
      Enhanced Transmission and Infant Morbidity.
AB  - A significant number of infants acquire HIV-1 through their infected mother's
      breast milk, primarily due to limited access to antiretrovirals. Passive
      immunization with neutralizing antibodies (nAbs) may prevent this transmission.
      Previous studies, however, have generated conflicting results about the ability
      of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant
      outcomes. This study compared plasma neutralizing activity in exposed infants and
      the infected mothers (n = 63) against heterologous HIV-1 variants and the
      quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n =
      42), compared to those that eventually acquired infection (n = 21), did not
      possess higher nAb responses against heterologous envelopes (P = 0.46) or their
      mothers' variants (P = 0.45). Transmitting compared to nontransmitting mothers,
      however, had significantly higher plasma neutralizing activity against
      heterologous envelopes (P = 0.03), although these two groups did not have
      significant differences in their ability to neutralize autologous strains (P =
      0.39). Furthermore, infants born to mothers with greater neutralizing breadth and
      potency were significantly more likely to have a serious adverse event (P =
      0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does
      not prevent breast milk transmission. Additionally, high maternal neutralizing
      breadth and potency may adversely influence both the frequency of breast milk
      transmission and subsequent infant morbidity.IMPORTANCE Passive immunization
      trials are under way to understand if preexisting antibodies can decrease mother
      to-child HIV-1 transmission and improve infant outcomes. We examined the
      influence of preexisting maternal and infant neutralizing activity on
      transmission and infant morbidity in a breastfeeding mother-infant cohort.
      Neutralization was examined against both the exposure strains circulating in the
      infected mothers and a standardized reference panel previously used to estimate
      breadth. HIV-exposed uninfected infants did not possess a broader and more potent
      response against both the exposure and heterologous strains compared to infants
      that acquired infection. Transmitting, compared to nontransmitting, mothers had
      significantly higher neutralization breadth and potency but similar responses
      against autologous variants. Infants born to mothers with higher neutralization
      responses were more likely to have a serious adverse event. Our results suggest
      that preexisting antibodies do not protect against breast milk HIV-1 acquisition
      and may have negative consequences for the baby.

PMID- 29066545
TI  - Tuning of the Lethal Response to Multiple Stressors with a Single-Site Mutation
      during Clinical Infection by Staphylococcus aureus.
AB  - The agr system of Staphylococcus aureus promotes invasion of host tissues, and as
      expected, agents that block agr quorum sensing have anti-infective properties.
      Paradoxically, agr-defective mutants are frequently recovered from patients,
      especially those persistently infected with S. aureus We found that an agr
      deficiency increased survival of cultured bacteria during severe stress, such as
      treatment with gentamicin, ciprofloxacin, heat, or low pH. With daptomycin,
      deletion of agr decreased survival. Therefore, agr activity can be either
      detrimental or protective, depending on the type of lethal stress. Deletion of
      agr had no effect on the ability of the antimicrobials to block bacterial growth,
      indicating that agr effects are limited to lethal action. Thus, the effect of an
      agr deletion is on bacterial tolerance, not resistance. For gentamicin and
      daptomycin, activity can be altered by agr-regulated secreted factors. For
      ciprofloxacin, a detrimental function was downregulation of glutathione
      peroxidase (bsaA), an enzyme responsible for defense against oxidative stress.
      Deficiencies in agr and bsaA were epistatic for survival, consistent with agr
      having a destructive role mediated by reactive oxygen species. Enhanced
      susceptibility to lethal stress by wild-type agr, particularly antimicrobial
      stress, helps explain why inactivating mutations in S. aureus agr commonly occur
      in hospitalized patients during infection. Moreover, the agr quorum-sensing
      system of S. aureus provides a clinically relevant example in which a single-step
      change in the response to severe stress alters the evolutionary path of a
      pathogen during infection.IMPORTANCE When phenotypes produced in response to an
      environmental stress are inadequate to buffer against that stress, changes that
      do buffer may become genetically encoded by natural selection. A clinically
      relevant example is seen with S. aureus mutants that are deficient in the key
      virulence regulator agr Paradoxically, defects in agr are selected during serious
      hospital infection and have been associated with worse outcome. The current work
      helps resolve this paradox: agr mutants are often less readily killed by lethal
      stressors without affecting MIC, a phenomenon known as tolerance. Our results
      indicate that tolerance, which would not be detected as resistance, can be
      selected in clinical settings. The data also support the ideas that (i) S. aureus
      broadly hedges against environmental change and stress through genome plasticity,
      (ii) reactive oxygen can be involved in the self-destructive response in
      bacteria, and (iii) therapeutic targeting of agr and virulence can be
      counterproductive.

PMID- 29066546
TI  - Adaptation to Chronic Nutritional Stress Leads to Reduced Dependence on
      Microbiota in Drosophila melanogaster.
AB  - Numerous studies have shown that animal nutrition is tightly linked to gut
      microbiota, especially under nutritional stress. In Drosophila melanogaster,
      microbiota are known to promote juvenile growth, development, and survival on
      poor diets, mainly through enhanced digestion leading to changes in hormonal
      signaling. Here, we show that this reliance on microbiota is greatly reduced in
      replicated Drosophila populations that became genetically adapted to a poor
      larval diet in the course of over 170 generations of experimental evolution.
      Protein and polysaccharide digestion in these poor-diet-adapted populations
      became much less dependent on colonization with microbiota. This was accompanied
      by changes in expression levels of dFOXO transcription factor, a key regulator of
      cell growth and survival, and many of its targets. These evolutionary changes in
      the expression of dFOXO targets to a large degree mimic the response of the same
      genes to microbiota, suggesting that the evolutionary adaptation to poor diet
      acted on mechanisms that normally mediate the response to microbiota. Our study
      suggests that some metazoans have retained the evolutionary potential to adapt
      their physiology such that association with microbiota may become optional rather
      than essential.IMPORTANCE Animals depend on gut microbiota for various metabolic
      tasks, particularly under conditions of nutritional stress, a relationship
      usually regarded as an inherent aspect of animal physiology. Here, we use
      experimental evolution in fly populations to show that the degree of host
      dependence on microbiota can substantially and rapidly change as the host
      population evolves in response to poor diet. Our results suggest that, although
      microbiota may initially greatly facilitate coping with suboptimal diets, chronic
      nutritional stress experienced over multiple generations leads to evolutionary
      adaptation in physiology and gut digestive properties that reduces dependence on
      the microbiota for growth and survival. Thus, despite its ancient evolutionary
      history, the reliance of animal hosts on their microbial partners can be
      surprisingly flexible and may be relaxed by short-term evolution.

PMID- 29066547
TI  - Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells
      during Mycobacterium tuberculosis Infection.
AB  - Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF-/-)
      are highly susceptible to infection with Mycobacterium tuberculosis, and clinical
      data have shown that anti-GM-CSF neutralizing antibodies can lead to increased
      susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates
      human and murine macrophages to inhibit intracellular M. tuberculosis growth. We
      have previously shown that GM-CSF produced by iNKT cells inhibits growth of M.
      tuberculosis However, the more general role of T cell-derived GM-CSF during
      infection has not been defined and how GM-CSF activates macrophages to inhibit
      bacterial growth is unknown. Here we demonstrate that, in addition to
      nonconventional T cells, conventional T cells also produce GM-CSF during M.
      tuberculosis infection. Early during infection, nonconventional iNKT cells and
      gammadelta T cells are the main source of GM-CSF, a role subsequently assumed by
      conventional CD4+ T cells as the infection progresses. M. tuberculosis-specific T
      cells producing GM-CSF are also detected in the peripheral blood of infected
      people. Under conditions where nonhematopoietic production of GM-CSF is
      deficient, T cell production of GM-CSF is protective and required for control of
      M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated
      protection in settings where GM-CSF is produced by other cell types. Finally,
      using an in vitro macrophage infection model, we demonstrate that GM-CSF
      inhibition of M. tuberculosis growth requires the expression of peroxisome
      proliferator-activated receptor gamma (PPARgamma). Thus, we identified GM-CSF
      production as a novel T cell effector function. These findings suggest that a
      strategy augmenting T cell production of GM-CSF could enhance host resistance
      against M. tuberculosisIMPORTANCEMycobacterium tuberculosis is the bacterium that
      causes tuberculosis, the leading cause of death by any infection worldwide. T
      cells are critical components of the immune response to Mycobacterium
      tuberculosis While gamma interferon (IFN-gamma) is a key effector function of T
      cells during infection, a failed phase IIb clinical trial and other studies have
      revealed that IFN-gamma production alone is not sufficient to control M.
      tuberculosis In this study, we demonstrate that CD4+, CD8+, and nonconventional T
      cells produce GM-CSF during Mycobacterium tuberculosis infection in mice and in
      the peripheral blood of infected humans. Under conditions where other sources of
      GM-CSF are absent, T cell production of GM-CSF is protective and is required for
      control of infection. GM-CSF activation of macrophages to limit bacterial growth
      requires host expression of the transcription factor PPARgamma. The
      identification of GM-CSF production as a T cell effector function may inform
      future host-directed therapy or vaccine designs.

PMID- 29066548
TI  - Genome-Wide Discovery of Genes Required for Capsule Production by Uropathogenic
      Escherichia coli.
AB  - Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract and
      bloodstream infections and possesses an array of virulence factors for
      colonization, survival, and persistence. One such factor is the polysaccharide K
      capsule. Among the different K capsule types, the K1 serotype is strongly
      associated with UPEC infection. In this study, we completely sequenced the K1
      UPEC urosepsis strain PA45B and employed a novel combination of a lytic K1
      capsule-specific phage, saturated Tn5 transposon mutagenesis, and high-throughput
      transposon-directed insertion site sequencing (TraDIS) to identify the complement
      of genes required for capsule production. Our analysis identified known genes
      involved in capsule biosynthesis, as well as two additional regulatory genes
      (mprA and lrhA) that we characterized at the molecular level. Mutation of mprA
      resulted in protection against K1 phage-mediated killing, a phenotype restored by
      complementation. We also identified a significantly increased unidirectional Tn5
      insertion frequency upstream of the lrhA gene and showed that strong expression
      of LrhA induced by a constitutive Pcl promoter led to loss of capsule production.
      Further analysis revealed loss of MprA or overexpression of LrhA affected the
      transcription of capsule biosynthesis genes in PA45B and increased sensitivity to
      killing in whole blood. Similar phenotypes were also observed in UPEC strains
      UTI89 (K1) and CFT073 (K2), demonstrating that the effects were neither strain
      nor capsule type specific. Overall, this study defined the genome of a UPEC
      urosepsis isolate and identified and characterized two new regulatory factors
      that affect UPEC capsule production.IMPORTANCE Urinary tract infections (UTIs)
      are among the most common bacterial infections in humans and are primarily caused
      by uropathogenic Escherichia coli (UPEC). Many UPEC strains express a
      polysaccharide K capsule that provides protection against host innate immune
      factors and contributes to survival and persistence during infection. The K1
      serotype is one example of a polysaccharide capsule type and is strongly
      associated with UPEC strains that cause UTIs, bloodstream infections, and
      meningitis. The number of UTIs caused by antibiotic-resistant UPEC is steadily
      increasing, highlighting the need to better understand factors (e.g., the
      capsule) that contribute to UPEC pathogenesis. This study describes the original
      and novel application of lytic capsule-specific phage killing, saturated Tn5
      transposon mutagenesis, and high-throughput transposon-directed insertion site
      sequencing to define the entire complement of genes required for capsule
      production in UPEC. Our comprehensive approach uncovered new genes involved in
      the regulation of this key virulence determinant.

PMID- 29066551
TI  - Reply to "Chronic Vaginal Candidiasis Is Achievable in Outbred CD-1 Mice".

PMID- 29066549
TI  - Selective Proteomic Analysis of Antibiotic-Tolerant Cellular Subpopulations in
      Pseudomonas aeruginosa Biofilms.
AB  - Biofilm infections exhibit high tolerance against antibiotic treatment. The study
      of biofilms is complicated by phenotypic heterogeneity; biofilm subpopulations
      differ in their metabolic activities and their responses to antibiotics. Here, we
      describe the use of the bio-orthogonal noncanonical amino acid tagging (BONCAT)
      method to enable selective proteomic analysis of a Pseudomonas aeruginosa biofilm
      subpopulation. Through controlled expression of a mutant methionyl-tRNA
      synthetase, we targeted BONCAT labeling to cells in the regions of biofilm
      microcolonies that showed increased tolerance to antibiotics. We enriched and
      identified proteins synthesized by cells in these regions. Compared to the entire
      biofilm proteome, the labeled subpopulation was characterized by a lower
      abundance of ribosomal proteins and was enriched in proteins of unknown function.
      We performed a pulse-labeling experiment to determine the dynamic proteomic
      response of the tolerant subpopulation to supra-MIC treatment with the
      fluoroquinolone antibiotic ciprofloxacin. The adaptive response included the
      upregulation of proteins required for sensing and repairing DNA damage and
      substantial changes in the expression of enzymes involved in central carbon
      metabolism. We differentiated the immediate proteomic response, characterized by
      an increase in flagellar motility, from the long-term adaptive strategy, which
      included the upregulation of purine synthesis. This targeted, selective analysis
      of a bacterial subpopulation demonstrates how the study of proteome dynamics can
      enhance our understanding of biofilm heterogeneity and antibiotic
      tolerance.IMPORTANCE Bacterial growth is frequently characterized by behavioral
      heterogeneity at the single-cell level. Heterogeneity is especially evident in
      the physiology of biofilms, in which distinct cellular subpopulations can respond
      differently to stresses, including subpopulations of pathogenic biofilms that are
      more tolerant to antibiotics. Global proteomic analysis affords insights into
      cellular physiology but cannot identify proteins expressed in a particular
      subpopulation of interest. Here, we report a chemical biology method to
      selectively label, enrich, and identify proteins expressed by cells within
      distinct regions of biofilm microcolonies. We used this approach to study changes
      in protein synthesis by the subpopulation of antibiotic-tolerant cells throughout
      a course of treatment. We found substantial differences between the initial
      response and the long-term adaptive strategy that biofilm cells use to cope with
      antibiotic stress. The method we describe is readily applicable to investigations
      of bacterial heterogeneity in diverse contexts.

PMID- 29066550
TI  - Comparative Genomic Analysis of Globally Dominant ST131 Clone with Other
      Epidemiologically Successful Extraintestinal Pathogenic Escherichia coli (ExPEC)
      Lineages.
AB  - Escherichia coli sequence type 131 (ST131), a pandemic clone responsible for the
      high incidence of extraintestinal pathogenic E. coli (ExPEC) infections, has been
      known widely for its contribution to the worldwide dissemination of multidrug
      resistance. Although other ExPEC-associated and extended-spectrum-beta-lactamase
      (ESBL)-producing E. coli clones, such as ST38, ST405, and ST648 have been studied
      widely, no comparative genomic data with respect to other genotypes exist for
      ST131. In this study, comparative genomic analysis was performed for 99 ST131 E.
      coli strains with 40 genomes from three other STs, including ST38 (n = 12), ST405
      (n = 10), and ST648 (n = 18), and functional studies were performed on five in
      house strains corresponding to the four STs. Phylogenomic analysis results from
      this study corroborated with the sequence type-specific clonality. Results from
      the genome-wide resistance profiling confirmed that all strains were inherently
      multidrug resistant. ST131 genomes showed unique virulence profiles, and analysis
      of mobile genetic elements and their associated methyltransferases (MTases) has
      revealed that several of them were missing from the majority of the non-ST131
      strains. Despite the fact that non-ST131 strains lacked few essential genes
      belonging to the serum resistome, the in-house strains representing all four STs
      demonstrated similar resistance levels to serum antibactericidal activity. Core
      genome analysis data revealed that non-ST131 strains usually lacked several ST131
      defined genomic coordinates, and a significant number of genes were missing from
      the core of the ST131 genomes. Data from this study reinforce adaptive
      diversification of E. coli strains belonging to the ST131 lineage and provide new
      insights into the molecular mechanisms underlying clonal diversification of the
      ST131 lineage.IMPORTANCEE. coli, particularly the ST131 extraintestinal
      pathogenic E. coli (ExPEC) lineage, is an important cause of community- and
      hospital-acquired infections, such as urinary tract infections, surgical site
      infections, bloodstream infections, and sepsis. The treatment of infections
      caused by ExPEC has become very challenging due to the emergence of resistance to
      the first-line as well as the last-resort antibiotics. This study analyzes E.
      coli ST131 against three other important and globally distributed ExPEC lineages
      (ST38, ST405, and ST648) that also produced extended-spectrum beta-lactamase
      (ESBL). This is perhaps the first study that employs the high-throughput whole
      genome sequence-based approach to compare and study the genomic features of these
      four ExPEC lineages in relation to their functional properties. Findings from
      this study highlight the differences in the genomic coordinates of ST131 with
      respect to the other STs considered here. Results from this comparative genomics
      study can help in advancing the understanding of ST131 evolution and also offer a
      framework towards future developments in pathogen identification and targeted
      therapeutics to prevent diseases caused by this pandemic E. coli ST131 clone.

PMID- 29066553
TI  - Stimulation of the Locus Ceruleus Modulates Signal-to-Noise Ratio in the
      Olfactory Bulb.
AB  - Norepinephrine (NE) has been shown to influence sensory, and specifically
      olfactory processing at the behavioral and physiological levels, potentially by
      regulating signal-to-noise ratio (S/N). The present study is the first to look at
      NE modulation of olfactory bulb (OB) in regards to S/N in vivo We show, in male
      rats, that locus ceruleus stimulation and pharmacological infusions of NE into
      the OB modulate both spontaneous and odor-evoked neural responses. NE in the OB
      generated a non-monotonic dose-response relationship, suppressing mitral cell
      activity at high and low, but not intermediate, NE levels. We propose that NE
      enhances odor responses not through direct potentiation of the afferent signal
      per se, but rather by reducing the intrinsic noise of the system. This has
      important implications for the ways in which an animal interacts with its
      olfactory environment, particularly as the animal shifts from a relaxed to an
      alert behavioral state.SIGNIFICANCE STATEMENT Sensory perception can be modulated
      by behavioral states such as hunger, fear, stress, or a change in environmental
      context. Behavioral state often affects neural processing via the release of
      circulating neurochemicals such as hormones or neuromodulators. We here show that
      the neuromodulator norepinephrine modulates olfactory bulb spontaneous activity
      and odor responses so as to generate an increased signal-to-noise ratio at the
      output of the olfactory bulb. Our results help interpret and improve existing
      ideas for neural network mechanisms underlying behaviorally observed improvements
      in near-threshold odor detection and discrimination.

PMID- 29066552
TI  - FKBP12-Dependent Inhibition of Calcineurin Mediates Immunosuppressive Antifungal
      Drug Action in Malassezia.
AB  - The genus Malassezia includes yeasts that are commonly found on the skin or hair
      of animals and humans as commensals and are associated with a number of skin
      disorders. We have previously developed an Agrobacterium tumefaciens
      transformation system effective for both targeted gene deletion and insertional
      mutagenesis in Malassezia furfur and M. sympodialis In the present study, these
      molecular resources were applied to characterize the immunophilin FKBP12 as the
      target of tacrolimus (FK506), ascomycin, and pimecrolimus, which are calcineurin
      inhibitors that are used as alternatives to corticosteroids in the treatment of
      inflammatory skin disorders such as those associated with Malassezia species.
      While M. furfur and M. sympodialis showed in vitro sensitivity to these agents,
      fkb1Delta mutants displayed full resistance to all three of them, confirming that
      FKBP12 is the target of these calcineurin inhibitors and is essential for their
      activity. We found that calcineurin inhibitors act additively with fluconazole
      through an FKBP12-dependent mechanism. Spontaneous M. sympodialis isolates
      resistant to calcineurin inhibitors had mutations in the gene encoding FKBP12 in
      regions predicted to affect the interactions between FKBP12 and FK506 based on
      structural modeling. Due to the presence of homopolymer nucleotide repeats in the
      gene encoding FKBP12, an msh2Delta hypermutator of M. sympodialis was engineered
      and exhibited an increase of more than 20-fold in the rate of emergence of
      resistance to FK506 compared to that of the wild-type strain, with the majority
      of the mutations found in these repeats.IMPORTANCEMalassezia species are the most
      abundant fungal components of the mammalian and human skin microbiome. Although
      they belong to the natural skin commensal flora of humans, they are also
      associated with a variety of clinical skin disorders. The standard treatment for
      Malassezia-associated inflammatory skin infections is topical corticosteroids,
      although their use has adverse side effects and is not recommended for long
      treatment periods. Calcineurin inhibitors have been proposed as a suitable
      alternative to treat patients affected by skin lesions caused by Malassezia
      Although calcineurin inhibitors are well-known as immunosuppressive drugs, they
      are also characterized by potent antimicrobial activity. In the present study, we
      investigated the mechanism of action of FK506 (tacrolimus), ascomycin (FK520),
      and pimecrolimus in M. furfur and M. sympodialis and found that the conserved
      immunophilin FKBP12 is the target of these drugs with which it forms a complex
      that directly binds calcineurin and inhibits its signaling activity. We found
      that FKBP12 is also required for the additive activity of calcineurin inhibitors
      with fluconazole. Furthermore, the increasing natural occurrence in fungal
      pathogen populations of mutator strains poses a high risk for the rapid emergence
      of drug resistance and adaptation to host defense. This led us to generate an
      engineered hypermutator msh2Delta mutant strain of M. sympodialis and genetically
      evaluate mutational events resulting in a substantially increased rate of
      resistance to FK506 compared to that of the wild type. Our study paves the way
      for the novel clinical use of calcineurin inhibitors with lower immunosuppressive
      activity that could be used clinically to treat a broad range of fungal
      infections, including skin disorders caused by Malassezia.

PMID- 29066555
TI  - Recruitment of Foveal Retinotopic Cortex During Haptic Exploration of Shapes and
      Actions in the Dark.
AB  - The role of the early visual cortex and higher-order occipitotemporal cortex has
      been studied extensively for visual recognition and to a lesser degree for haptic
      recognition and visually guided actions. Using a slow event-related fMRI
      experiment, we investigated whether tactile and visual exploration of objects
      recruit the same "visual" areas (and in the case of visual cortex, the same
      retinotopic zones) and if these areas show reactivation during delayed actions in
      the dark toward haptically explored objects (and if so, whether this reactivation
      might be due to imagery). We examined activation during visual or haptic
      exploration of objects and action execution (grasping or reaching) separated by
      an 18 s delay. Twenty-nine human volunteers (13 females) participated in this
      study. Participants had their eyes open and fixated on a point in the dark. The
      objects were placed below the fixation point and accordingly visual exploration
      activated the cuneus, which processes retinotopic locations in the lower visual
      field. Strikingly, the occipital pole (OP), representing foveal locations, showed
      higher activation for tactile than visual exploration, although the stimulus was
      unseen and location in the visual field was peripheral. Moreover, the lateral
      occipital tactile-visual area (LOtv) showed comparable activation for tactile and
      visual exploration. Psychophysiological interaction analysis indicated that the
      OP showed stronger functional connectivity with anterior intraparietal sulcus and
      LOtv during the haptic than visual exploration of shapes in the dark. After the
      delay, the cuneus, OP, and LOtv showed reactivation that was independent of the
      sensory modality used to explore the object. These results show that haptic
      actions not only activate "visual" areas during object touch, but also that this
      information appears to be used in guiding grasping actions toward targets after a
      delay.SIGNIFICANCE STATEMENT Visual presentation of an object activates shape
      processing areas and retinotopic locations in early visual areas. Moreover, if
      the object is grasped in the dark after a delay, these areas show "reactivation."
      Here, we show that these areas are also activated and reactivated for haptic
      object exploration and haptically guided grasping. Touch-related activity occurs
      not only in the retinotopic location of the visual stimulus, but also at the
      occipital pole (OP), corresponding to the foveal representation, even though the
      stimulus was unseen and located peripherally. That is, the same "visual" regions
      are implicated in both visual and haptic exploration; however, touch also
      recruits high-acuity central representation within early visual areas during both
      haptic exploration of objects and subsequent actions toward them. Functional
      connectivity analysis shows that the OP is more strongly connected with ventral
      and dorsal stream areas when participants explore an object in the dark than when
      they view it.

PMID- 29066554
TI  - Cortical Regulation of Nociception of the Trigeminal Nucleus Caudalis.
AB  - Pain perception is strongly influenced by descending pathways from "higher" brain
      centers that regulate the activity of spinal circuits. In addition to the
      extensively studied descending system originating from the medulla, the neocortex
      provides dense anatomical projections that directly target neurons in the spinal
      cord and the spinal trigeminal nucleus caudalis (SpVc). Evidence exists that
      these corticotrigeminal pathways may modulate the processing of nociceptive
      inputs by SpVc, and regulate pain perception. We demonstrate here, with
      anatomical and optogenetic methods, and using both rats and mice (of both sexes),
      that corticotrigeminal axons densely innervate SpVc, where they target and
      directly activate inhibitory and excitatory neurons. Electrophysiological
      recordings reveal that stimulation of primary somatosensory cortex potently
      suppresses SpVc responses to noxious stimuli and produces behavioral hypoalgesia.
      These findings demonstrate that the corticotrigeminal pathway is a potent
      modulator of nociception and a potential target for interventions to alleviate
      chronic pain.SIGNIFICANCE STATEMENT Many chronic pain conditions are resistant to
      conventional therapy. Promising new approaches to pain management capitalize on
      the brain's own mechanisms for controlling pain perception. Here we demonstrate
      that cortical neurons directly innervate the brainstem to drive feedforward
      inhibition of nociceptive neurons. This corticotrigeminal pathway suppresses the
      activity of these neurons and produces analgesia. This corticotrigeminal pathway
      may constitute a therapeutic target for chronic pain.

PMID- 29066556
TI  - Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity
      Patterns in Different Thalamic Nuclei.
AB  - The thalamus plays diverse roles in cortical-subcortical brain activity patterns.
      Recent work suggests that focal temporal lobe seizures depress subcortical
      arousal systems and convert cortical activity into a pattern resembling slow-wave
      sleep. The potential simultaneous and paradoxical role of the thalamus in both
      limbic seizure propagation, and in sleep-like cortical rhythms has not been
      investigated. We recorded neuronal activity from the central lateral (CL),
      anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an
      established female rat model of focal limbic seizures. We found that population
      firing of neurons in CL decreased during seizures while the cortex exhibited slow
      waves. In contrast, ANT showed a trend toward increased neuronal firing
      compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile,
      VPM exhibited a remarkable increase in sleep spindles during focal seizures.
      Single-unit juxtacellular recordings from CL demonstrated reduced overall firing
      rates, but a switch in firing pattern from single spikes to burst firing during
      seizures. These findings suggest that different thalamic nuclei play very
      different roles in focal limbic seizures. While limbic nuclei, such as ANT,
      appear to participate directly in seizure propagation, arousal nuclei, such as
      CL, may contribute to depressed cortical function, whereas sleep spindles in
      relay nuclei, such as VPM, may interrupt thalamocortical information flow. These
      combined effects could be critical for controlling both seizure severity and
      impairment of consciousness. Further understanding of differential effects of
      seizures on different thalamocortical networks may lead to improved treatments
      directly targeting these modes of impaired function.SIGNIFICANCE STATEMENT
      Temporal lobe epilepsy has a major negative impact on quality of life. Previous
      work suggests that the thalamus plays a critical role in thalamocortical network
      modulation and subcortical arousal maintenance, but its precise seizure
      associated functions are not known. We recorded neuronal activity in three
      different thalamic regions and found divergent activity patterns, which may
      respectively participate in seizure propagation, impaired level of conscious
      arousal, and altered relay of information to the cortex during focal limbic
      seizures. These very different activity patterns within the thalamus may help
      explain why focal temporal lobe seizures often disrupt widespread network
      function, and can help guide future treatments aimed at restoring normal
      thalamocortical network activity and cognition.

PMID- 29066557
TI  - Neuromedin B Expression Defines the Mouse Retrotrapezoid Nucleus.
AB  - The retrotrapezoid nucleus (RTN) consists, by definition, of Phox2b-expressing,
      glutamatergic, non-catecholaminergic, noncholinergic neurons located in the
      parafacial region of the medulla oblongata. An unknown proportion of RTN neurons
      are central respiratory chemoreceptors and there is mounting evidence for
      biochemical diversity among these cells. Here, we used multiplexed in situ
      hybridization and single-cell RNA-Seq in male and female mice to provide a more
      comprehensive view of the phenotypic diversity of RTN neurons. We now demonstrate
      that the RTN of mice can be identified with a single and specific marker,
      Neuromedin B mRNA (Nmb). Most (~75%) RTN neurons express low-to-moderate levels
      of Nmb and display chemoreceptor properties. Namely they are activated by
      hypercapnia, but not by hypoxia, and express proton sensors, TASK-2 and Gpr4.
      These Nmb-low RTN neurons also express varying levels of transcripts for Gal,
      Penk, and Adcyap1, and receptors for substance P, orexin, serotonin, and ATP. A
      subset of RTN neurons (~20-25%), typically larger than average, express very high
      levels of Nmb mRNA. These Nmb-high RTN neurons do not express Fos after
      hypercapnia and have low-to-undetectable levels of Kcnk5 or Gpr4 transcripts;
      they also express Adcyap1, but are essentially devoid of Penk and Gal
      transcripts. In male rats, Nmb is also a marker of the RTN but, unlike in mice,
      this gene is expressed by other types of nearby neurons located within the
      ventromedial medulla. In sum, Nmb is a selective marker of the RTN in rodents;
      Nmb-low neurons, the vast majority, are central respiratory chemoreceptors,
      whereas Nmb-high neurons likely have other functions.SIGNIFICANCE STATEMENT
      Central respiratory chemoreceptors regulate arterial PCO2 by adjusting lung
      ventilation. Such cells have recently been identified within the retrotrapezoid
      nucleus (RTN), a brainstem nucleus defined by genetic lineage and a cumbersome
      combination of markers. Using single-cell RNA-Seq and multiplexed in situ
      hybridization, we show here that a single marker, Neuromedin B mRNA (Nmb),
      identifies RTN neurons in rodents. We also suggest that >75% of these Nmb neurons
      are chemoreceptors because they are strongly activated by hypercapnia and express
      high levels of proton sensors (Kcnk5 and Gpr4). The other RTN neurons express
      very high levels of Nmb, but low levels of Kcnk5/Gpr4/pre-pro-galanin/pre-pro
      enkephalin, and do not respond to hypercapnia. Their function is unknown.

PMID- 29066558
TI  - Orientation Tuning of Correlated Activity in the Developing Lateral Geniculate
      Nucleus.
AB  - Neural circuits and the cells that comprise them undergo developmental changes in
      the spatial organization of their connections and in their temporal response
      properties. Within the lateral geniculate nucleus (LGN) of the dorsal thalamus,
      these changes have pronounced effects on the spatiotemporal receptive fields
      (STRFs) of neurons. An open and unresolved question is how STRF maturation
      affects stimulus-evoked correlated activity between pairs of LGN neurons during
      development. This is an important question to answer because stimulus-evoked
      correlated activity likely plays a role in establishing the specificity of
      thalamocortical connectivity and the receptive fields (RFs) of postsynaptic
      cortical neurons. Using multielectrode recording methods and white noise stimuli,
      we recorded neural activity from ensembles of LGN neurons in cats across early
      development. As expected, there was a progressive maturation of the spatial and
      temporal properties of visual responses. Using drifting bar stimuli and cross
      correlation analysis, we also determined the orientation-tuning bandwidth of
      correlated activity between pairs of LGN neurons at different stages of
      development (Sillito and Jones, 2002; Andolina et al., 2007; Stanley et al.,
      2012; Kelly et al., 2014). Despite the larger RFs and slower responses of
      immature LGN neurons compared with mature neurons, our results show that
      correlated activity in the LGN was as tightly tuned for orientation early in
      development as it was in the adult. Closer examination revealed this age
      invariant orientation tuning of correlated activity likely involves cellular
      mechanisms related to spike fatigue in young animals and a progressive decrease
      in response latency with development.SIGNIFICANCE STATEMENT Orientation tuning is
      a fundamental property of neurons in primary visual cortex. An important and
      unresolved question is how orientation tuning emerges during brain development.
      This study explores a potential mechanism for the establishment of orientation
      tuning based on correlated activity patterns among ensembles of maturing neurons
      in the lateral geniculate nucleus (LGN) of the thalamus. Results show that
      correlated activity between pairs of LGN neurons is more tightly tuned than
      predictions based simply on receptive field size, indicating that correlated
      activity has the properties needed to play an important role in the development
      of geniculocortical circuits and the emergence of cortical orientation tuning.

PMID- 29066559
TI  - Phosphoinositol-4,5-Bisphosphate Regulates Auditory Hair-Cell Mechanotransduction
      Channel Pore Properties and Fast Adaptation.
AB  - Membrane proteins, such as ion channels, interact dynamically with their lipid
      environment. Phosphoinositol-4,5-bisphosphate (PIP2) can directly or indirectly
      modify ion-channel properties. In auditory sensory hair cells of rats (Sprague
      Dawley) of either sex, PIP2 localizes within stereocilia, near stereocilia tips.
      Modulating the amount of free PIP2 in inner hair-cell stereocilia resulted in the
      following: (1) the loss of a fast component of mechanoelectric-transduction
      current adaptation, (2) an increase in the number of channels open at the hair
      bundle's resting position, (3) a reduction of single-channel conductance, (4) a
      change in ion selectivity, and (5) a reduction in calcium pore blocking effects.
      These changes occur without altering hair-bundle compliance or the number of
      functional stereocilia within a given hair bundle. Although the specific
      molecular mechanism for PIP2 action remains to be uncovered, data support a
      hypothesis for PIP2 directly regulating channel conformation to alter calcium
      permeation and single-channel conductance.SIGNIFICANCE STATEMENT How forces are
      relayed to the auditory mechanoelectrical transduction (MET) channel remains
      unknown. However, researchers have surmised that lipids might be involved.
      Previous work on bullfrog hair cells showed an effect of phosphoinositol-4,5
      bisphosphate (PIP2) depletion on MET current amplitude and adaptation, leading to
      the postulation of the existence of an underlying myosin-based adaptation
      mechanism. We find similar results in rat cochlea hair cells but extend these
      data to include single-channel analysis, hair-bundle mechanics, and channel
      permeation properties. These additional data attribute PIP2 effects to actions on
      MET-channel properties and not motor interactions. Further findings support
      PIP2's role in modulating a fast, myosin-independent, and Ca2+-independent
      adaptation process, validating fast adaptation's biological origin. Together this
      shows PIP2's pivotal role in auditory MET, likely as a direct channel modulator.

PMID- 29066563
TI  - Sensitivity and Specificity or Positive and Negative Percent Agreement? A Micro
      Comic Strip.

PMID- 29066561
TI  - Concerted Interneuron Activity in the Cerebellar Molecular Layer During Rhythmic
      Oromotor Behaviors.
AB  - Molecular layer interneurons (MLIs, stellate and basket cells) of the cerebellar
      cortex are linked together by chemical and electrical synapses and exert a potent
      feedforward inhibition on Purkinje cells. The functional role of MLIs during
      specific motor tasks is uncertain. Here, we used two-photon imaging to study the
      patterns of activity of neighboring individual MLIs in the Crus II region of
      awake female mice during two types of oromotor activity, licking and bruxing,
      using specific expression of the genetically encoded calcium indicator protein
      GCaMP6s. We found that both stellate and basket cells engaged in synchronized
      waves of calcium activity during licking and bruxing, with high degrees of
      correlation among the signals collected in individual MLIs. In contrast, no
      calcium activity was observed during whisking. MLI activity tended to lag behind
      the onset of sustained licking episodes, indicating a regulatory action of MLIs
      during licking. Furthermore, during licking, stellate cell activity was
      anisotropic: the coordination was constant along the direction of parallel fibers
      (PFs), but fell off with distance along the orthogonal direction. These results
      suggest a PF drive for Ca2+ signals during licking. In contrast, during bruxing,
      MLI activity was neither clearly organized spatially nor temporally correlated
      with oromotor activity. In conclusion, MLI activity exhibits a high degree of
      correlation both in licking and in bruxing, but spatiotemporal patterns of
      activity display significant differences for the two types of
      behavior.SIGNIFICANCE STATEMENT It is known that, during movement, the activity
      of molecular layer interneurons (MLIs) of the cerebellar cortex is enhanced.
      However, MLI-MLI interactions are complex because they depend both from
      excitatory electrical synapses and from potentially inhibitory chemical synapses.
      Accordingly, the pattern of MLI activity during movement has been unclear. Here,
      during two oromotor tasks, licking and bruxism, individual neighboring MLIs
      displayed highly coordinated activity, showing that the positive influences
      binding MLIs together are predominant. We further find that spatiotemporal
      patterns differ between licking and bruxing, suggesting that the precise pattern
      of MLI activity depends on the nature of the motor task.

PMID- 29066562
TI  - Photo Quiz: A 69-Year-Old Immunosuppressed Male with Chest Pain and Shortness of
      Breath.

PMID- 29066560
TI  - Direct Recording of Dendrodendritic Excitation in the Olfactory Bulb: Divergent
      Properties of Local and External Glutamatergic Inputs Govern Synaptic Integration
      in Granule Cells.
AB  - The olfactory bulb contains excitatory principal cells (mitral and tufted cells)
      that project to cortical targets as well as inhibitory interneurons. How the
      local circuitry in this region facilitates odor-specific output is not known, but
      previous work suggests that GABAergic granule cells plays an important role,
      especially during fine odor discrimination. Principal cells interact with granule
      cells through reciprocal dendrodendritic connections that are poorly understood.
      While many studies examined the GABAergic output side of these reciprocal
      connections, little is known about how granule cells are excited. Only two
      previous studies reported monosynaptically coupled mitral/granule cell
      connections and neither attempted to determine the fundamental properties of
      these synapses. Using dual intracellular recordings and a custom-built loose
      patch amplifier, we have recorded unitary granule cell EPSPs evoked in response
      to mitral cell action potentials in rat (both sexes) brain slices. We find that
      the unitary dendrodendritic input is relatively weak with highly variable release
      probability and short-term depression. In contrast with the weak dendrodendritic
      input, the facilitating cortical input to granule cells is more powerful and less
      variable. Our computational simulations suggest that dendrodendritic synaptic
      properties prevent individual principal cells from strongly depolarizing granule
      cells, which likely discharge in response to either concerted activity among a
      large proportion of inputs or coactivation of a smaller subset of local
      dendrodendritic inputs with coincidence excitation from olfactory cortex. This
      dual-pathway requirement likely enables the sparse mitral/granule cell
      interconnections to develop highly odor-specific responses that facilitate fine
      olfactory discrimination.SIGNIFICANCE STATEMENT The olfactory bulb plays a
      central role in converting broad, highly overlapping, sensory input patterns into
      odor-selective population responses. How this occurs is not known, but
      experimental and theoretical studies suggest that local inhibition often plays a
      central role. Very little is known about how the most common local interneuron
      subtype, the granule cell, is excited during odor processing beyond the unusual
      anatomical arraignment of the interconnections (reciprocal dendrodendritic
      synapses). Using paired recordings and two-photon imaging, we determined the
      properties of the primary input to granule cells for the first time and show that
      these connections bias interneurons to fire in response to spiking in large
      populations of principal cells rather than a small group of highly active cells.

PMID- 29066564
TI  - The Brief Case: Bacteremia and Vertebral Osteomyelitis Due to Staphylococcus
      schleiferi.

PMID- 29066565
TI  - Modern Hematology Analyzers Are Very Useful for Diagnosis of Malaria and,
      Crucially, May Help Avoid Misdiagnosis.

PMID- 29066566
TI  - Reply to "Modern Hematology Analyzers Are Very Useful for Diagnosis of Malaria
      and, Crucially, May Help Avoid Misdiagnosis".

PMID- 29066567
TI  - Integrated Stewardship Model Comprising Antimicrobial, Infection Prevention, and
      Diagnostic Stewardship (AID Stewardship).

PMID- 29066568
TI  - Reply to "Integrated Stewardship Model Comprising Antimicrobial, Infection
      Prevention, and Diagnostic Stewardship (AID Stewardship)".

PMID- 29066569
TI  - Closing the Brief Case: Bacteremia and Vertebral Osteomyelitis Due to
      Staphylococcus schleiferi.

PMID- 29066570
TI  - Answer to November 2017 Photo Quiz.

PMID- 29066571
TI  - Individual testosterone decline and future mortality risk in men.
AB  - OBJECTIVE: Male aging is characterized by a decline in testosterone (TS) levels
      with a substantial variability between subjects. However, it is unclear whether
      differences in age-related changes in TS are associated with general health. We
      investigated associations between mortality and intra-individual changes in serum
      levels of total TS, SHBG, free TS and LH during a ten-year period with up to 18
      years of registry follow-up. DESIGN: 1167 men aged 30-60 years participating in
      the Danish Monitoring Trends and Determinants of Cardiovascular Disease (MONICA1)
      study and who had a follow-up examination ten years later (MONICA10) were
      included. From MONICA10, the men were followed up to 18 years (mean: 15.2 years)
      based on the information from national mortality registries via their unique
      personal ID numbers. METHODS: Cox proportional hazard models were used to
      investigate the association between intra-individual hormone changes and all
      cause, CVD and cancer mortalities. RESULTS: A total of 421 men (36.1%) died
      during the follow-up period. Men with most pronounced decline in total TS (<10th
      percentile) had a higher all-cause mortality risk compared to men within the 10th
      to 90th percentile (hazard ratio (HR): 1.60; 95% confidence interval (CI): 1.08
      2.36). No consistent associations were seen in cause-specific mortality analyses.
      CONCLUSION: Our study showed that higher mortality rates were seen among the men
      who had the most pronounced age-related decline in TS, independent of their
      baseline TS levels.

PMID- 29066572
TI  - Time to parathyroid function recovery in patients with protracted
      hypoparathyroidism after total thyroidectomy.
AB  - OBJECTIVE: Hypocalcaemia is the most common adverse effect after total
      thyroidectomy. It recovers in about two-thirds of the patients within the first
      postoperative month. Little is known, however, about recovery of the parathyroid
      function (RPF) after this time period. The aim of the present study was to
      investigate the time to RPF in patients with protracted (>1 month)
      hypoparathyroidism after total thyroidectomy. DESIGN: Cohort prospective
      observational study. METHODS: Adult patients undergoing total thyroidectomy for
      goitre or thyroid cancer. Cases with protracted hypoparathyroidism were studied
      for RPF during the following months. Time to RPF and variables associated with
      RPF or permanent hypoparathyroidism were recorded. RESULTS: Out of 854 patients
      undergoing total thyroidectomy, 142 developed protracted hypoparathyroidism. Of
      these, 36 (4.2% of the entire cohort) developed permanent hypoparathyroidism and
      106 recovered: 73 before 6 months, 21 within 6-12 months and 12 after 1 year
      follow-up. Variables significantly associated with RPF were the number of
      parathyroid glands remaining in situ (not autografted nor inadvertently resected)
      and a serum calcium concentration >2.25 mmol/L at one postoperative month. Late
      RPF (>6 months) was associated with surgery for thyroid cancer. RPF was still
      possible after one year in patients with four parathyroid glands preserved in
      situ and serum calcium concentration at one month >2.25 mmol/L. CONCLUSIONS:
      Permanent hypoparathyroidism should not be diagnosed in patients requiring
      replacement therapy for more than six months, especially if the four parathyroid
      glands were preserved.

PMID- 29066573
TI  - Incidence, prevalence and seasonal onset variation of Addison's disease among
      persons with type 1 diabetes mellitus: nationwide, matched cohort studies.
AB  - OBJECTIVES: We determined the incidence and prevalence of Addison's disease (AD)
      among persons with or without type 1 diabetes mellitus (T1DM) in nationwide,
      matched cohort studies. METHODS: Persons with T1DM were identified from the
      Swedish National Diabetes Register and each was matched for age, sex, year and
      county to five controls randomly selected from the general population. Persons
      with AD were identified from the Swedish National Inpatient Register. Baseline
      demographics and seasonal onset variation of AD were presented by descriptive
      statistics. Prevalence and incidence were estimated by proportions and incidence
      rates, respectively. Times to AD were analyzed using the Cox proportional hazard
      model. RESULTS: Between 1998 and 2013, 66 persons with T1DM were diagnosed with
      AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM,
      while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570
      controls. The difference in mean age at diagnosis of AD between the groups was
      6.3 years (P value = 0.036). The incidence of AD for a person with or without
      T1DM was therefore 193 and 18 per million person-years, respectively. The
      adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1
      16.5). The highest incidence of AD was observed during February-March and
      September-October. The prevalence of AD in persons with or without T1DM in
      December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD
      in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5). CONCLUSION: The
      risk to develop AD among persons with T1DM is more than 10 times higher than in
      persons without T1DM. Persons with T1DM develop AD at a younger age. The
      incidence of AD may have a seasonal pattern.

PMID- 29066574
TI  - Low eukaryotic viral richness is associated with faecal microbiota
      transplantation success in patients with UC.

PMID- 29066575
TI  - CDK20 inhibition and immune checkpoint blockade: bringing cancer biology and
      tumour immunology together to develop novel treatment options for HCC.

PMID- 29066576
TI  - Real-time differentiation of adenomatous and hyperplastic diminutive colorectal
      polyps during analysis of unaltered videos of standard colonoscopy using a deep
      learning model.
AB  - BACKGROUND: In general, academic but not community endoscopists have demonstrated
      adequate endoscopic differentiation accuracy to make the 'resect and discard'
      paradigm for diminutive colorectal polyps workable. Computer analysis of video
      could potentially eliminate the obstacle of interobserver variability in
      endoscopic polyp interpretation and enable widespread acceptance of 'resect and
      discard'. STUDY DESIGN AND METHODS: We developed an artificial intelligence (AI)
      model for real-time assessment of endoscopic video images of colorectal polyps. A
      deep convolutional neural network model was used. Only narrow band imaging video
      frames were used, split equally between relevant multiclasses. Unaltered videos
      from routine exams not specifically designed or adapted for AI classification
      were used to train and validate the model. The model was tested on a separate
      series of 125 videos of consecutively encountered diminutive polyps that were
      proven to be adenomas or hyperplastic polyps. RESULTS: The AI model works with a
      confidence mechanism and did not generate sufficient confidence to predict the
      histology of 19 polyps in the test set, representing 15% of the polyps. For the
      remaining 106 diminutive polyps, the accuracy of the model was 94% (95% CI 86% to
      97%), the sensitivity for identification of adenomas was 98% (95% CI 92% to
      100%), specificity was 83% (95% CI 67% to 93%), negative predictive value 97% and
      positive predictive value 90%. CONCLUSIONS: An AI model trained on endoscopic
      video can differentiate diminutive adenomas from hyperplastic polyps with high
      accuracy. Additional study of this programme in a live patient clinical trial
      setting to address resect and discard is planned.

PMID- 29066577
TI  - Identification and characterization of T reg-like cells in zebrafish.
AB  - Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that
      suppress autoreactive T cells. Functional studies of T reg cells in vitro have
      defined multiple suppression mechanisms, and studies of T reg-deficient humans
      and mice have made clear the important role that these cells play in preventing
      autoimmunity. However, many questions remain about how T reg cells act in vivo.
      Specifically, it is not clear which suppression mechanisms are most important,
      where T reg cells act, and how they get there. To begin to address these issues,
      we sought to identify T reg cells in zebrafish, a model system that provides
      unparalleled advantages in live-cell imaging and high-throughput genetic
      analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched,
      mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a
      displayed excess T lymphocytes, splenomegaly, and a profound inflammatory
      phenotype that was suppressed by genetic ablation of lymphocytes. This study
      identifies T reg-like cells in zebrafish, providing both a model to study the
      normal functions of these cells in vivo and mutants to explore the consequences
      of their loss.

PMID- 29066579
TI  - Insight Into Long-term Neurodevelopmental Outcomes in Asymptomatic Congenital CMV
      Infection.

PMID- 29066578
TI  - R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus
      host disease.
AB  - The intestinal microbial ecosystem is actively regulated by Paneth cell-derived
      antimicrobial peptides such as alpha-defensins. Various disorders, including
      graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in
      unfavorably altered intestinal microbiota (dysbiosis), which further accelerates
      the underlying diseases. Current strategies to restore the gut ecosystem are
      bacteriotherapy such as fecal microbiota transplantation and probiotics, and no
      physiological approach has been developed so far. In this study, we demonstrate a
      novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R
      Spo1) or recombinant alpha-defensin in mice. R-Spo1 stimulates intestinal stem
      cells to differentiate to Paneth cells and enhances luminal secretion of alpha
      defensins. Administration of R-Spo1 or recombinant alpha-defensin prevents GVHD
      mediated dysbiosis, thus representing a novel and physiological approach at
      modifying the gut ecosystem to restore intestinal homeostasis and host-microbiota
      cross talk toward therapeutic benefits.

PMID- 29066581
TI  - Reducing Time to Antibiotics in Children With Intestinal Failure, Central Venous
      Line, and Fever.
AB  - BACKGROUND: Children with intestinal failure (IF) on parenteral nutrition (PN)
      are at high risk for bacteremia, and delays in antibiotic administration have
      been associated with increased morbidity and mortality. We designed an emergency
      department (ED) quality improvement (QI) initiative to reduce time to
      administration of intravenous antibiotics in febrile children with IF on PN.
      METHODS: Our aim was to decrease the mean time for febrile children with IF on PN
      to receive intravenous antibiotics by 50% to <60 minutes over a 12-month period.
      Secondary outcome measures were ED, hospital, and ICU length of stay (LOS). Our
      process measure was the rate of ordering recommended antibiotics, and our
      balancing measure was the rate of hypoglycemia. Interventions included increasing
      provider knowledge of IF, streamlining order entry, providing individualized
      feedback, and standardizing the triage process. Results were analyzed by using
      statistical process control methodology and time series analysis. RESULTS: We
      identified 149 eligible ED patients, of which 62 (41.6%) had bacteremia. The mean
      time to antibiotics decreased after the onset of the QI initiative from 112 to 39
      minutes, and the ED LOS decreased from 286 to 247 minutes, but the total length
      of hospital and ICU stays were unchanged. The rate of hypoglycemia was also
      unchanged. CONCLUSIONS: Our QI intervention for febrile children with IF on PN
      shortened the time to receive antibiotics. Larger studies are needed to
      demonstrate the impact on overall LOS and mortality.

PMID- 29066580
TI  - Intelligence and Academic Achievement With Asymptomatic Congenital
      Cytomegalovirus Infection.
AB  - OBJECTIVES: To examine intelligence, language, and academic achievement through
      18 years of age among children with congenital cytomegalovirus infection
      identified through hospital-based newborn screening who were asymptomatic at
      birth compared with uninfected infants. METHODS: We used growth curve modeling to
      analyze trends in IQ (full-scale, verbal, and nonverbal intelligence), receptive
      and expressive vocabulary, and academic achievement in math and reading. Separate
      models were fit for each outcome, modeling the change in overall scores with
      increasing age for patients with normal hearing (n = 78) or with sensorineural
      hearing loss (SNHL) diagnosed by 2 years of age (n = 11) and controls (n = 40).
      RESULTS: Patients with SNHL had full-scale intelligence and receptive vocabulary
      scores that were 7.0 and 13.1 points lower, respectively, compared with controls,
      but no significant differences were noted in these scores among patients with
      normal hearing and controls. No significant differences were noted in scores for
      verbal and nonverbal intelligence, expressive vocabulary, and academic
      achievement in math and reading among patients with normal hearing or with SNHL
      and controls. CONCLUSIONS: Infants with asymptomatic congenital cytomegalovirus
      infection identified through newborn screening with normal hearing by age 2 years
      do not appear to have differences in IQ, vocabulary or academic achievement
      scores during childhood, or adolescence compared with uninfected children.

PMID- 29066583
TI  - Lack of data sharing in observational studies.

PMID- 29066584
TI  - Predicting 30-Day All-Cause Readmission Risk for Subjects Admitted With Pneumonia
      at the Point of Care.
AB  - BACKGROUND: The pneumonia 30-d readmission rate has been endorsed by the National
      Quality Forum as a quality metric. Hospital readmissions can potentially be
      lowered by improving in-hospital care, transitions of care, and post-discharge
      disease management programs. The purpose of this study was to create an accurate
      prediction model for determining the risk of 30-d readmission at the point of
      discharge. METHODS: The model was created using a data set of 1,295
      hospitalizations at the Cleveland Clinic Main Campus with pneumonia over 3 y.
      Candidate variables were limited to structured variables available in the
      electronic health record. The final model was compared with the Centers for
      Medicare and Medicaid Services (CMS) model among subjects 65 y of age and older
      (n = 628) and was externally validated. RESULTS: Three hundred thirty subjects
      (25%) were readmitted within 30 d. The final model contained 13 variables and had
      a bias-corrected C statistic of 0.74 (95% CI 0.71-0.77). Number of admissions in
      the prior 6 months, opioid prescription, serum albumin during the first 24 h,
      international normalized ratio and blood urea nitrogen during the last 24 h were
      the predictor variables with the greatest weight in the model. In terms of
      discriminative performance, the Cleveland Clinic model outperformed the CMS model
      on the validation cohort (C statistic 0.69 vs 0.60, P = .042). CONCLUSIONS: The
      proposed risk prediction model performed better than the CMS model. Accurate
      readmission risk prediction at the point of discharge is feasible and can
      potentially be used to focus post-acute care interventions in a high-risk group
      of patients.

PMID- 29066585
TI  - Use of Cardiac Cycle Locating to Minimize the Influence of Cardiac Artifacts on
      Esophageal Pressure Measurement During Dynamic Occlusion Test.
AB  - BACKGROUND: The dynamic occlusion test is used to guide balloon catheter
      placement during esophageal pressure (Pes) monitoring. We introduced a cardiac
      cycle locating method to attenuate the influence of cardiac artifacts on Pes
      measurement. The aim was to provide a reliable analytic algorithm for the
      occlusion test. METHODS: Esophageal balloon catheters were placed in subjects
      receiving pressure support ventilation. During balloon position adjustment, end
      expiratory occlusion was performed to induce 3 consecutive inspiratory efforts.
      Pes and airway pressure (Paw) data were collected for off-line analysis. For each
      occluded inspiratory effort, the change in Pes (DeltaPes) was plotted against the
      change in Paw (DeltaPaw), and the slope of the regression line was calculated.
      The DeltaPes/DeltaPaw ratio was also measured with the cardiac cycle locating
      method and peak-to-peak method. Bland-Altman analysis was used to assess the
      agreement between the DeltaPes/DeltaPaw ratio and the slope. We defined the
      occlusion test with all fitted slopes for the 3 inspiratory efforts within 0.8 to
      1.2 to indicate optimal balloon position; otherwise, the position was deemed non
      optimal. Using the slope as the reference, the diagnostic accuracy of the
      DeltaPes/DeltaPaw ratio in distinguishing the optimal and the non-optimal balloon
      position was analyzed. RESULTS: A total of 86 occlusion tests containing 258
      inspiratory efforts were collected from 15 subjects. The median (interquartile
      range) slope of DeltaPes versus DeltaPaw plot was 0.85 (0.76, 0.91). Bias (lower
      and upper limit of agreement) of DeltaPes/DeltaPaw ratio measured by the cardiac
      cycle locating method and the peak-to-peak method was 0.02 (-0.13 to 0.16) and
      0.06 (-0.18 to 0.31), respectively. Forty-five (52.3%) occlusion tests indicated
      optimal balloon positions. Compared to the peak-to-peak method, the cardiac cycle
      locating method was more specific in detecting the non-optimal position.
      CONCLUSIONS: The cardiac cycle locating method provided reliable and precise
      measurement for the occlusion test. This method can accurately detect non-optimal
      balloon position during catheter adjustment.

PMID- 29066586
TI  - Mechanical Insufflation-Exsufflation Versus Conventional Chest Physiotherapy in
      Children With Cerebral Palsy.
AB  - BACKGROUND: The cough mechanism is often impaired in children with quadriplegic
      spastic cerebral palsy, accounting for the high prevalence of pneumonia and
      atelectasis requiring prolonged hospitalization. Conventional chest physiotherapy
      (CPT) is a current technique recommended at the onset of lower-respiratory
      infections in cerebral palsy. Previous studies have demonstrated the usefulness
      of mechanical insufflation-exsufflation (MI-E) in children with neuromuscular
      disease. To date, there has been no study of MI-E in children with quadriplegic
      spastic cerebral palsy. The objective of the study is to compare the efficacy in
      reducing hospital stay and improvement of atelectasis between MI-E and CPT in
      children with quadriplegic spastic cerebral palsy with lower-respiratory
      infections. METHODS: This study is a randomized controlled trial. Children with
      quadriplegic spastic cerebral palsy, age 6 months to 18 y, admitted for lower
      respiratory infections and/or atelectasis at King Chulalongkorn Memorial Hospital
      between June 1, 2014, and March 31, 2015, were recruited. Those with
      pneumothorax, severe pneumonia, active tuberculosis, and shock were excluded.
      Children were randomized into the MI-E or CPT group. The MI-E group received MI-E
      (3 therapies/d), and the CPT group received CPT (1 therapy/d). Vital signs per
      protocol and chest radiograph as needed were recorded. RESULTS: There were 22
      children enrolled in the study, 11 in the MI-E and 11 in the CPT group.
      Demographic data were comparable in both groups. The length of hospital stay was
      similar in both groups (MI-E 4-24 d vs CPT 6-42 d, P = .15). There were 17
      subjects with atelectasis (MI-E [n = 9] versus CPT [n = 8]). In this atelectasis
      subgroup, MI-E had shortened therapy time when compared with CPT (2.9 +/- 0.8 d
      vs 3.9 +/- 0.6 d, P = .01). No complications were observed. CONCLUSIONS: MI-E is
      proven to be beneficial in shortening the duration of airway clearance in
      children with quadriplegic spastic cerebral palsy presenting with lower
      respiratory infections and atelectasis. MI-E is a safe and efficient intervention
      for airway clearance.

PMID- 29066587
TI  - Heart Rate Variability in Extremely Preterm Infants Receiving Nasal CPAP and Non
      Synchronized Noninvasive Ventilation Immediately After Extubation.
AB  - INTRODUCTION: There is a paucity of studies comparing the physiological effects
      of nasal CPAP or non-synchronized noninvasive ventilation (ns-NIV) during the
      postextubation phase in preterm infants. Heart rate variability (HRV) can
      identify system instability before clinical or laboratory signs of deterioration.
      Thus, we sought to investigate any differences in HRV between those modes.
      METHODS: 15 preterm infants with birthweight <=1,250 g and undergoing their first
      extubation attempt were studied immediately after disconnection from mechanical
      ventilation. Electrocardiogram (ECG) recordings were obtained while on nasal CPAP
      and ns-NIV in a random order (30-60 min on each). Time and frequency domain
      analyses were used to calculate HRV from 5-min segments of ECG. RESULTS: 12 of 15
      infants were analyzed (3 were excluded for low ECG quality): 7 successes and 5
      failures. HRV parameters were higher during ns-NIV when compared to nasal CPAP,
      but differences were not statistically different. However, absolute and relative
      differences in HRV values (all time domain parameters) were significantly higher
      in infants who failed extubation during ns-NIV. CONCLUSIONS: Nasal CPAP or ns-NIV
      provided immediately postextubation did not affect HRV. Interestingly, in an
      exploratory analysis, changes in HRV did occur during ns-NIV in the subgroup of
      infants who failed extubation. Hence, changes in HRV as early as 2 h after
      extubation should be further explored in larger studies as a potential predictor
      of postextubation respiratory failure.

PMID- 29066588
TI  - Effect of High-Flow Nasal Cannula on Expiratory Pressure and Ventilation in
      Infant, Pediatric, and Adult Models.
AB  - BACKGROUND: Heated and humidified high-flow nasal cannula (HFNC) is a widely used
      form of respiratory support; however, data regarding optimal flows for a given
      patient size or disease state are lacking. A comprehensive study of the
      physiologic effects of HFNC is needed to better understand the mechanisms of
      action. The objective of the current study was to quantify the effect of HFNC
      settings in age-specific, anatomically correct nasal airways and spontaneously
      breathing lung models. We hypothesized that there is an effect of flow on
      pressure and ventilation. METHODS: Three-dimensionally printed upper airway
      models of a preterm neonate, term neonate, toddler, small child, and adult were
      affixed to the ASL 5000 test lung to simulate spontaneous breathing with age
      appropriate normal ventilation parameters. CO2 was introduced to simulate
      profound hypercapneic respiratory failure with an end-tidal partial pressure of
      carbon dioxide (PETCO2 ) of 90 +/- 1 mm Hg. Two commercially available HFNC
      systems were applied to the airway models, and PEEP, inspired CO2, and exhaled
      CO2 (PETCO2 ) were recorded for 6 min across a range of flow. RESULTS: Increasing
      HFNC flow provided a non-linear increase in PEEP in closed-mouth models, with
      maximum tested flows generating 6 cm H2O in the preterm neonate to 20 cm H2O in
      the small child. Importantly, PEEP decreased by approximately 50% in open-mouth
      models. Increasing HFNC flow improved expiratory CO2 elimination to a certain
      point, above which continued increases in flow had minimal additional effect.
      This change point ranged from 4 L/min in the preterm neonate to 10 L/min in the
      small child. CONCLUSIONS: These findings may help clinicians understand the
      effects of HFNC at different settings and may inform management guidelines for
      patients with respiratory failure.

PMID- 29066589
TI  - Economic Assessment of 4 Approaches to the Diagnosis and Initial Treatment of
      Sleep Apnea.
AB  - BACKGROUND: A dilemma faced by health-care administrators is that need greatly
      outstrips capacity for diagnosing and treating sleep apnea, with such decisions
      carrying significant economic consequences. Our objective was to develop an
      economic model to estimate the relative costs of 4 approaches for diagnosis and
      initial treatment of sleep apnea. METHODS: The analysis consisted of developing a
      mathematical model depicting possible diagnostic and treatment approaches to the
      care of patients with sleep apnea; developing 4 clinical scenarios to describe
      distinct approaches to the management of sleep apnea patients (in-laboratory,
      unattended, direct-to-autotitrating PAP [auto-PAP], and mixed); and identifying
      costs associated with each scenario. We created a hypothetical cohort of 1,000
      patients with 85% prevalence of sleep apnea to generate cost estimates. RESULTS:
      The driver of per-patient costs was the total number of sleep studies, which
      varied widely across scenarios: from 425 for the direct-to-auto-PAP approach to
      1,441 in the unattended approach. The scenarios also differed in per-patient
      costs: Per-patient costs excluding facility startup costs were $456 for direct-to
      auto-PAP, $913 for in-laboratory, $991 for mixed, and $1,090 for unattended.
      CONCLUSIONS: Approaches to diagnosing and treating sleep apnea that emphasized
      early application of auto-PAP had lower per-patient costs.

PMID- 29066590
TI  - Development and Feasibility of a Home Pulmonary Rehabilitation Program With
      Health Coaching.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is an effective intervention for COPD.
      However, traditional center-based PR programs suffer from low uptake. Home-based
      PR is a viable solution, but few studies have shown the effectiveness of remote
      PR, as there is a scarcity of systems that can be easily adopted in clinical
      practice. The aim of this report is to communicate the development and
      feasibility of a home PR program that includes commercially available technology
      that allows the PR health coach to follow the patient through his or her PR
      process and to present the design of a prospective clinical trial. METHODS: We
      developed a home PR system that includes a computer tablet, an activity monitor,
      and an oximeter connected to a cloud server. The home PR consists of 12 min of
      walking and 6 full-body exercises, to be completed 6 d/week, plus weekly
      telephone calls with the PR health coach. Two pilot studies were conducted in
      subjects with moderate-to-severe COPD. The first aimed to fine-tune the system
      development (N = 3), and the second tested the program feasibility of the 8-week
      program (N = 12). RESULTS: In pilot study 1, PR monitoring data from the
      subjects' home PR sessions were transmitted to the health coach application
      successfully. On a 10-point scale, participants rated the system as helpful
      (median = 8, interquartile range 8-9) and simple to use (median = 10,
      interquartile range 9-10). In pilot study 2, adherence +/- SD for prescribed use
      was 87 +/- 0.24%. Overall, participants gave the home PR system a rating of 6.2
      +/- 0.94 on a 7-point scale. CONCLUSIONS: A home PR program was developed that
      integrated health coaching and a home PR system that facilitated remote
      monitoring. Pilot testing indicated that the program is well-developed and
      feasible in a population of individuals with COPD. (ClinicalTrials.gov
      registration NCT02999685.).

PMID- 29066592
TI  - A "Frank Statement" for the 21st Century?

PMID- 29066591
TI  - The Role of Rescue Therapies in the Treatment of Severe ARDS.
AB  - ARDS is characterized by a non-cardiogenic pulmonary edema with bilateral chest
      radiograph opacities and hypoxemia refractory to oxygen therapy. It is a common
      cause of admission to the ICU due to hypoxemic respiratory failure requiring
      mechanical ventilation. Corticosteroids are not recommended in ARDS patients.
      Rescue therapies alleviate hypoxemia in patients unable to maintain reasonable
      oxygenation: recruitment maneuvers, prone positioning, inhaled nitric oxide, high
      frequency oscillatory ventilation, and extracorporeal membrane oxygenation
      improve oxygenation, but their impact on mortality remains unproven. Restrictive
      fluid management seems to be a favorable strategy with no significant reduction
      in 60-d mortality. Future studies are needed to clarify the efficacy of these
      therapies on outcomes in patients with severe ARDS, and institution of these
      therapies may be considered on a case-by-case basis.

PMID- 29066593
TI  - Costs, revenues and profits: an economic analysis of smallholder tobacco farmer
      livelihoods in Malawi.
AB  - BACKGROUND: The preservation of the economic livelihood of tobacco farmers is a
      common argument used to oppose tobacco control measures. However, little
      empirical evidence exists about these livelihoods. We seek to evaluate the
      economic livelihoods of individual tobacco farmers in Malawi, including how much
      money they earn from selling tobacco, and the costs they incur to produce the
      crop, including labour inputs. We also evaluate farmers' decisions to contract
      directly with firms that buy their crops. METHODS: We designed and implemented an
      economic survey of 685 tobacco farmers, including both independent and contract
      farmers, across the 6 main tobacco-growing districts. We augmented the survey
      with focus group discussions with subsets of respondents from each region to
      refine our inquiries. RESULTS: Contract farmers cultivating tobacco in Malawi as
      their main economic livelihoods are typically operating at margins that place
      their households well below national poverty thresholds, while independent
      farmers are typically operating at a loss. Even when labour is excluded from the
      calculation of income less costs, farmers' gross margins place most households in
      the bottom income decile of the overall population. Tobacco farmers appear to
      contract principally as a means to obtain credit, which is consistently reported
      to be difficult to obtain. CONCLUSIONS: The tobacco industry narrative that
      tobacco farming is a lucrative economic endeavour for smallholder farmers is
      demonstrably inaccurate in the context of Malawi. From the perspective of these
      farmers, tobacco farming is an economically challenging livelihood for most.

PMID- 29066595
TI  - Physiological effects of high-altitude trekking on gonadal, thyroid hormones and
      macrophage migration inhibitory factor (MIF) responses in young lowlander women.
AB  - Altitude hypoxia is often associated with impairment of human reproduction. In
      this study, hormones and macrophage migration inhibitory factor (MIF, a
      proinflammatory cytokine with key roles in human reproduction) were determined in
      seven regularly menstruating, lowlander native women living at sea level
      participating in 14 days of trekking at moderate and high altitude. Blood and
      saliva samples were collected from each subject at high altitude (5050 m a.s.l.
      [above sea level]), and at sea level before and after the expedition.
      Testosterone level was lowered by high altitude and was restored after the end of
      the expedition, while progesterone decreased significantly in all participants at
      the end of the expedition, although most of the participants were in the luteal
      phase. The salivary concentration of MIF decreased greatly at altitude, but its
      levels were completely restored after the return to sea level. Our findings
      showed high sensitivity and rapid changes in the determined parameters in
      response to the high-altitude hypoxic environment, particularly MIF.

PMID- 29066598
TI  - Erratum. Deletion of p66Shc Longevity Gene Protects Against Experimental Diabetic
      Glomerulopathy by Preventing Diabetes-Induced Oxidative Stress. Diabetes
      2006;55:1642-1650.

PMID- 29066596
TI  - Abundance, localization, and functional correlates of the advanced glycation end
      product carboxymethyl lysine in human myocardium.
AB  - Advanced glycation end-products (AGEs) play a role in the pathophysiology of
      diabetes mellitus (DM) and possibly hypertension (HTN). In experimental DM, AGEs
      accumulate in myocardium. Little is known about AGEs in human myocardium. We
      quantified abundance, localization, and functional correlates of the AGE
      carboxymethyl lysine (CML) in left ventricular (LV) myocardium from patients
      undergoing coronary bypass grafting (CBG). Immunoelectron microscopy was used to
      quantify CML in epicardial biopsies from 98 patients (71 M, 27 F) with HTN, HTN +
      DM or neither (controls), all with normal LV ejection fraction. Myofilament
      contraction-relaxation function was measured in demembranated myocardial strips.
      Echocardiography was used to quantify LV structure and function. We found that
      CML was abundant within cardiomyocytes, but minimally associated with
      extracellular collagen. CML counts/MUm2 were 14.7% higher in mitochondria than
      the rest of the cytoplasm (P < 0.001). There were no significant sex or
      diagnostic group differences in CML counts [controls 45.6 +/- 3.6/MUm2 (+/-SEM),
      HTN 45.8 +/- 3.6/MUm2, HTN + DM 49.3 +/- 6.2/MUm2; P = 0.85] and no significant
      correlations between CML counts and age, HgbA1c or myofilament function indexes.
      However, left atrial volume was significantly correlated with CML counts (r =
      0.41, P = 0.004). We conclude that in CBG patients CML is abundant within
      cardiomyocytes but minimally associated with collagen, suggesting that AGEs do
      not directly modify the stiffness of myocardial collagen. Coexistent HTN or HTN +
      DM do not significantly influence CML abundance. The correlation of CML counts
      with LAV suggests an influence on diastolic function independent of HTN, DM or
      sex whose mechanism remains to be determined.

PMID- 29066597
TI  - Muscle oxygenation profiles between active and inactive muscles with nitrate
      supplementation under hypoxic exercise.
AB  - Whether dietary nitrate supplementation improves exercise performance or not is
      still controversial. While redistribution of sufficient oxygen from inactive to
      active muscles is essential for optimal exercise performance, no study
      investigated the effects of nitrate supplementation on muscle oxygenation
      profiles between active and inactive muscles. Nine healthy males performed 25 min
      of submaximal (heart rate ~140 bpm; EXsub) and incremental cycling (EXmax) until
      exhaustion under three conditions: (A) normoxia without drink; (B) hypoxia (FiO2
      = 13.95%) with placebo (PL); and (c) hypoxia with beetroot juice (BR). PL and BR
      were provided for 4 days. Oxygenated and deoxygenated hemoglobin (HbO2 and HHb)
      were measured in vastus lateralis (active) and biceps brachii (inactive) muscles,
      and the oxygen saturation of skeletal muscle (StO2; HbO2/total Hb) were
      calculated. During EXsub, BR suppressed the HHb increases in active muscles
      during the last 5 min of exercise. During EXmax, time to exhaustion with BR (513
      +/- 24 sec) was significantly longer than with PL (490 +/- 39 sec, P < 0.05). In
      active muscles, BR suppressed the HHb increases at moderate work rates during
      EXmax compared to PL (P < 0.05). In addition, BR supplementation was associated
      with greater reductions in HbO2 and StO2 at higher work rates in inactive muscles
      during EXmax Collectively, these findings indicate that short-term dietary
      nitrate supplementation improved hypoxic exercise tolerance, perhaps, due to
      suppressed increases in HHb in active muscles at moderate work rates. Moreover,
      nitrate supplementation caused greater reductions in oxygenation in inactive
      muscle at higher work rates during hypoxic exercise.

PMID- 29066599
TI  - IL-6-Type Cytokine Signaling in Adipocytes Induces Intestinal GLP-1 Secretion.
AB  - We recently showed that interleukin (IL)-6-type cytokine signaling in adipocytes
      induces free fatty acid release from visceral adipocytes, thereby promoting
      obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type
      cytokines may increase the release of leptin from adipocytes and by those means
      induce glucagon-like peptide 1 (GLP-1) secretion. We thus hypothesized that IL-6
      type cytokine signaling in adipocytes may regulate insulin secretion. To this
      end, mice with adipocyte-specific knockout of gp130, the signal transducer
      protein of IL-6, were fed a high-fat diet for 12 weeks. Compared with control
      littermates, knockout mice showed impaired glucose tolerance and circulating
      leptin, GLP-1, and insulin levels were reduced. In line, leptin release from
      isolated adipocytes was reduced, and intestinal proprotein convertase
      subtilisin/kexin type 1 (Pcsk1) expression, the gene encoding PC1/3, which
      controls GLP-1 production, was decreased in knockout mice. Importantly, treatment
      with the GLP-1 receptor antagonist exendin 9-39 abolished the observed difference
      in glucose tolerance between control and knockout mice. Ex vivo, supernatant
      collected from isolated adipocytes of gp130 knockout mice blunted Pcsk1
      expression and GLP-1 release from GLUTag cells. In contrast, glucose- and GLP-1
      stimulated insulin secretion was not affected in islets of knockout mice. In
      conclusion, adipocyte-specific IL-6 signaling induces intestinal GLP-1 release to
      enhance insulin secretion, thereby counteracting insulin resistance in obesity.

PMID- 29066601
TI  - What sort of death matters?

PMID- 29066600
TI  - Evidence That Differences in Fructosamine-3-Kinase Activity May Be Associated
      With the Glycation Gap in Human Diabetes.
AB  - The phenomenon of a discrepancy between glycated hemoglobin levels and other
      indicators of average glycemia may be due to many factors but can be measured as
      the glycation gap (GGap). This GGap is associated with differences in
      complications in patients with diabetes and may possibly be explained by
      dissimilarities in deglycation in turn leading to altered production of advanced
      glycation end products (AGEs). We hypothesized that variations in the level of
      the deglycating enzyme fructosamine-3-kinase (FN3K) might be associated with the
      GGap. We measured erythrocyte FN3K concentrations and enzyme activity in a
      population dichotomized for a large positive or negative GGap. FN3K protein was
      higher and we found a striking threefold greater activity (323%) at any given
      FN3K protein level in the erythrocytes of the negative-GGap group compared with
      the positive-GGap group. This was associated with lower AGE levels in the
      negative-GGap group (79%), lower proinflammatory adipokines (leptin-to
      adiponectin ratio) (73%), and much lower prothrombotic PAI-1 levels (19%). We
      conclude that FN3K may play a key role in the GGap and thus diabetes
      complications such that FN3K may be a potential predictor of the risk of diabetes
      complications. Pharmacological modifications of its activity may provide a novel
      approach to their prevention.

PMID- 29066602
TI  - In appreciation: Charles M. Tipton and the history of physiology.

PMID- 29066603
TI  - Reminiscing about Jan Evangelista Purkinje: a pioneer of modern experimental
      physiology.
AB  - This article reminisces about the life and key scientific achievements of Jan
      Evangelista Purkinje (1787-1869), a versatile 19th century Czech pioneer of
      modern experimental physiology. In 1804, after completing senior high school,
      Purkinje joined the Piarist monk order, but, after a 3-yr novitiate, he gave up
      the religious calling "to deal more freely with science." In 1818, he earned a
      Medical Doctor degree from Prague University by defending a dissertation on
      intraocular phenomena observed in oneself. In 1823, Purkinje became a Physiology
      and Pathology professor at the Prussian Medical University in Breslau, where he
      innovated the traditional teaching methods of physiology. Purkinje's
      contributions to physiology were manifold: accurate descriptions of various
      visual phenomena (e.g., Purkinje-Sanson images, Purkinje phenomenon), discovery
      of the terminal network of the cardiac conduction system (Purkinje fibers),
      identification of cerebellar neuronal bodies (Purkinje cells), formulation of the
      vertigo law (Purkinje's law), discovery of criteria to classify human
      fingerprints, etc. In 1850, Purkinje accepted and held until his death the
      Physiology chair at Prague Medical Faculty. During this period, he succeeded in
      introducing the Czech idiom (in addition to long-established German and Latin) as
      a Medical Faculty teaching language. Additionally, as a zealous Czech patriot, he
      actively contributed to the naissance and consolidation of a national Czech
      identity conscience. Purkinje was a trend-setting scientist who, throughout his
      career, worked to pave the way for the renovation of physiology from a
      speculative discipline, ancilla of anatomy, into a factual, autonomous science
      committed to the discovery of mechanisms governing in-life functions.

PMID- 29066604
TI  - The control of ventilation during exercise: a lesson in critical thinking.
AB  - Learning the basic competencies of critical thinking are very important in the
      education of any young scientist, and teachers must be prepared to help students
      develop a valuable set of analytic tools. In my experience, this is best achieved
      by encouraging students to study areas with little scientific consensus, such as
      the control mechanisms of the exercise ventilatory response, as it can allow
      greater objectivity when evaluating evidence, while also giving students the
      freedom to think independently and problem solve. In this article, I discuss
      teaching strategies by which physiology, biomedical science, and sport science
      students can simultaneously develop their understanding of respiratory control
      mechanisms and learn to critically analyze evidence thoroughly. This can be best
      achieved by utilizing both teacher-led and student-led learning environments, the
      latter of which encourages the development of learner autonomy and independent
      problem solving. In this article, I also aim to demonstrate a systematic approach
      of critical assessment that students can be taught, adapt, and apply
      independently. Among other things, this strategy involves: 1) defining the
      precise phenomenon in question; 2) understanding what investigations must
      demonstrate to explain the phenomenon and its underlying mechanisms; 3)
      evaluating the explanations/mechanisms of the phenomenon and the evidence for
      them; and 4) forming strategies to produce strong evidence, if none exists.

PMID- 29066605
TI  - Evaluation of performance and perceptions of electronic vs. paper multiple-choice
      exams.
AB  - In the veterinary professional curriculum, methods of examination in many courses
      are transitioning from the traditional paper-based exams to electronic-based
      exams. Therefore, a controlled trial to evaluate the impact of testing
      methodology on examination performance in a veterinary physiology course was
      designed and implemented. Formalized surveys and focus group discussions were
      also used to determine student attitudes toward the examination formats. In
      total, 134 first-year veterinary students and 11 PhD/MS students were
      administered a total of 4 exams throughout 1 semester (2 on paper and 2
      electronically) using a split-halves design. The paper (P) and electronic (E)
      exams contained 25 identical multiple-choice questions. Students were randomly
      assigned to two groups and were given exams in one of two sequences (E-P-E-P or P
      E-P-E). Participants consented to and completed two anonymous surveys vis a vis
      their experience. Out of a maximum raw score of 25, the mean score for electronic
      examinations (20.8; 95% confidence interval, 20.3-21.2) was significantly (P =
      0.01) greater than that for paper examinations (20.3; 95% confidence interval,
      20.0-20.7). However, students expressed numerous concerns with the electronic
      examination format, and, at the completion of the study, 87% preferred to take
      their examination on paper rather than the electronic format. These data show
      that student attitudes concerning the examination format are not primarily
      determined by examination results, and that the additional anxiety related to the
      electronic examination format plays a large role in student attitudes.

PMID- 29066606
TI  - Which way do the ions go? A graph-drawing exercise for understanding
      electrochemical gradients.

PMID- 29066607
TI  - Cancer cells, on your histone marks, get SETDB1, silence retrotransposons, and
      go!
AB  - Cancer cells thrive on genetic and epigenetic changes that confer a selective
      advantage but also need strategies to avoid immune recognition. In this issue,
      Cuellar et al. (2017. J. Cell Biol https://doi.org/10.1083/jcb.201612160) find
      that the histone methyltransferase SETDB1 enables acute myeloid leukemia cells to
      evade sensing of retrotransposons by innate immune receptors.

PMID- 29066610
TI  - High-sensitivity cardiac troponin I and risk of cardiovascular disease in an
      Australianpopulation-based cohort.
AB  - OBJECTIVE: High-sensitivity cardiac troponin I (hs-cTnI) is an emerging biomarker
      for cardiovascular risk. We examined hs-cTnI as a predictor of mortality and
      cardiovascular outcomes in an Australian population-based cohort and evaluated if
      a sex difference exists. METHODS: Serum hs-cTnI was measured in the Busselton
      Health Study 1994/1995 Cohort (n=3939). Outcome measures were total and
      cardiovascular mortality, cardiovascular disease (CVD) and coronary heart disease
      (CHD) events, heart failure and stroke. RESULTS: Hs-cTnI was detectable (>1.2
      ng/L) in 66.1% of participants (males 81.8%, females 54.4%) at baseline. There
      were 886 deaths (including 361 from CVD) and 940 CVD events during 20-year follow
      up. Adjusting for Framingham Risk Score variables, hs-cTnI was a significant
      predictor of total mortality (HR (95% CI): 1.16 (1.09 to 1.24)), CVD mortality
      (1.33 (1.23 to 1.44)), CVD events (1.18 (1.11 to 1.25)), CHD events (1.11 (1.03
      to 1.20)), heart failure (1.44 (1.31 to 1.58)) and stroke (1.13 (1.03 to 1.24))
      per doubling of hs-cTnI at baseline. HRs remained significant in CVD-free
      individuals at baseline (n=3215), except for CHD events. There were no
      significant interactions between sex and hs-cTnI as a predictor of outcomes.
      Compared with individuals with hs-cTnI <=1.2 ng/L, men with hs-cTnI >=6.0 ng/L
      and women with hs-cTnI >=4.0 ng/L had an HR of 2.18 (1.42 to 3.37) and 1.84 (1.30
      to 2.62), respectively, for any CVD event, which persisted in the CVD-free
      subgroup. CONCLUSIONS: Cardiac troponin I, measured with a high-sensitive assay,
      is an independent predictor of fatal and non-fatal CVD events and may help
      identify at-risk individuals in a general population.

PMID- 29066608
TI  - Molecular mechanisms of developmentally programmed crinophagy in Drosophila.
AB  - At the onset of metamorphosis, Drosophila salivary gland cells undergo a burst of
      glue granule secretion to attach the forming pupa to a solid surface. Here, we
      show that excess granules evading exocytosis are degraded via direct fusion with
      lysosomes, a secretory granule-specific autophagic process known as crinophagy.
      We find that the tethering complex HOPS (homotypic fusion and protein sorting);
      the small GTPases Rab2, Rab7, and its effector, PLEKHM1; and a SNAP receptor
      complex consisting of Syntaxin 13, Snap29, and Vamp7 are all required for the
      fusion of secretory granules with lysosomes. Proper glue degradation within
      lysosomes also requires the Uvrag-containing Vps34 lipid kinase complex and the v
      ATPase proton pump, whereas Atg genes involved in macroautophagy are dispensable
      for crinophagy. Our work establishes the molecular mechanism of developmentally
      programmed crinophagy in Drosophila and paves the way for analyzing this process
      in metazoans.

PMID- 29066609
TI  - Membrane curvature directs the localization of Cdc42p to novel foci required for
      cell-cell fusion.
AB  - Cell fusion is ubiquitous in eukaryotic fertilization and development. The highly
      conserved Rho-GTPase Cdc42p promotes yeast fusion through interaction with Fus2p,
      a pheromone-induced amphiphysin-like protein. We show that in prezygotes, Cdc42p
      forms a novel Fus2p-dependent focus at the center of the zone of cell fusion
      (ZCF) and remains associated with remnant cell walls after initial fusion. At the
      ZCF and during fusion, Cdc42p and Fus2p colocalized. In contrast, in shmoos, both
      proteins were near the cortex but spatially separate. Cdc42p focus formation
      depends on ZCF membrane curvature: mutant analysis showed that Cdc42p
      localization is negatively affected by shmoo-like positive ZCF curvature,
      consistent with the flattening of the ZCF during fusion. BAR-domain proteins such
      as the fusion proteins Fus2p and Rvs161p are known to recognize membrane
      curvature. We find that mutations that disrupt binding of the Fus2p/Rvs161p
      heterodimer to membranes affect Cdc42p ZCF localization. We propose that Fus2p
      localizes Cdc42p to the flat ZCF to promote cell wall degradation.

PMID- 29066611
TI  - Prognostic validation of a non-laboratory and a laboratory based cardiovascular
      disease risk score in multiple regions of the world.
AB  - OBJECTIVE: To evaluate the performance of the non-laboratory INTERHEART risk
      score (NL-IHRS) to predict incident cardiovascular disease (CVD) across seven
      major geographic regions of the world. The secondary objective was to evaluate
      the performance of the fasting cholesterol-based IHRS (FC-IHRS). METHODS: Using
      measures of discrimination and calibration, we tested the performance of the NL
      IHRS (n=100 475) and FC-IHRS (n=107 863) for predicting incident CVD in a
      community-based, prospective study across seven geographic regions: South Asia,
      China, Southeast Asia, Middle East, Europe/North America, South America and
      Africa. CVD was defined as the composite of cardiovascular death, myocardial
      infarction, stroke, heart failure or coronary revascularisation. RESULTS: Mean
      age of the study population was 50.53 (SD 9.79) years and mean follow-up was 4.89
      (SD 2.24) years. The NL-IHRS had moderate to good discrimination for incident CVD
      across geographic regions (concordance statistic (C-statistic) ranging from 0.64
      to 0.74), although recalibration was necessary in all regions, which improved its
      performance in the overall cohort (increase in C-statistic from 0.69 to 0.72,
      p<0.001). Regional recalibration was also necessary for the FC-IHRS, which also
      improved its overall discrimination (increase in C-statistic from 0.71 to 0.74,
      p<0.001). In 85 078 participants with complete data for both scores,
      discrimination was only modestly better with the FC-IHRS compared with the NL
      IHRS (0.74 vs 0.73, p<0.001). CONCLUSIONS: External validations of the NL-IHRS
      and FC-IHRS suggest that regionally recalibrated versions of both can be useful
      for estimating CVD risk across a diverse range of community-based populations.
      CVD prediction using a non-laboratory score can provide similar accuracy to
      laboratory-based methods.

PMID- 29066612
TI  - A systematic review of health promotion intervention studies in the police force:
      study characteristics, intervention design and impacts on health.
AB  - To systematically review studies of health promotion intervention in the police
      force. Four databases were searched for articles reporting on prepost single and
      multigroup studies in police officers and trainees. Data were extracted and bias
      assessed to evaluate study characteristics, intervention design and the impact of
      interventions on health. Database searching identified 25 articles reporting on
      21 studies relevant to the aims of this review. Few studies (n=3) were of long
      duration (>=6 months). Nine of 21 studies evaluated structured physical activity
      and/or diet programmes only, 5 studies used education and behaviour change
      support-only interventions, 5 combined structured programmes with education and
      behaviour change support, and 2 studies used computer prompts to minimise
      sedentary behaviour. A wide array of lifestyle behaviour and health outcomes was
      measured, with 11/13 multigroup and 8/8 single-group studies reporting beneficial
      impacts on outcomes. High risk of bias was evident across most studies. In those
      with the lowest risk of bias (n=2), a large effect on blood pressure and small
      effects on diet, sleep quality, stress and tobacco use, were reported. Health
      promotion interventions can impact beneficially on health of the police force,
      particularly blood pressure, diet, sleep, stress and tobacco use. Limited
      reporting made comparison of findings challenging. Combined structured programmes
      with education and behaviour change support and programmes including peer support
      resulted in the most impact on health-related outcomes.

PMID- 29066613
TI  - Severe negative energy balance during 21 d at high altitude decreases fat-free
      mass regardless of dietary protein intake: a randomized controlled trial.
AB  - In this 2-phase randomized controlled study, we examined whether consuming a
      higher-protein (HP) diet would attenuate fat-free mass (FFM) loss during energy
      deficit (ED) at high altitude (HA) in 17 healthy males (mean +/- sd: 23 +/- 6 yr;
      82 +/- 14 kg). During phase 1 at sea level (SL, 55 m), participants consumed a
      eucaloric diet providing standard protein (SP; 1.0 g protein/kg,) for 21 d.
      During phase 2, participants resided at HA (4300 m) for 22 d and were randomly
      assigned to either an SP or HP (2.0 g protein/kg) diet designed to elicit a 40%
      ED. Body composition, substrate oxidation, and postabsorptive whole-body protein
      kinetics were measured. Participants were weight stable during SL and lost 7.9 +/
      1.9 kg ( P < 0.01) during HA, regardless of dietary protein intake. Decrements
      in whole-body FFM (3.6 +/- 2.4 kg) and fat mass (3.6 +/- 1.3 kg) were not
      different between SP and HP. HP oxidized 0.95 +/- 0.32 g protein/kg per day more
      than SP and whole-body net protein balance was more negative for HP than for SP (
      P < 0.01). Based on changes in body energy stores, the overall ED was 70% (-1849
      +/- 511 kcal/d, no group differences). Consuming an HP diet did not protect FFM
      during severe ED at HA.-Berryman, C. E., Young, A. J., Karl, J. P., Kenefick, R.
      W., Margolis, L. M., Cole, R. E., Carbone, J. W., Lieberman, H. R., Kim, I.-Y.,
      Ferrando, A. A., Pasiakos, S. M. Severe negative energy balance during 21 d at
      high altitude decreases fat-free mass regardless of dietary protein intake: a
      randomized controlled trial.

PMID- 29066614
TI  - Targeting the Stat6 pathway in tumor-associated macrophages reduces tumor growth
      and metastatic niche formation in breast cancer.
AB  - Tumor-associated macrophages (TAMs) are the key effector cells in the tumor
      microenvironment and induce neoangiogenesis, matrix remodeling, and metastasis
      while suppressing the tumor immune system. These protumoral macrophages display
      an M2 phenotype induced by IL-4 and IL-13 cytokines. In this study, we
      hypothesized that the inhibition of the signal transducer and activator of
      transcription 6 (Stat6) pathway, a common downstream signaling pathway of IL-4
      and IL-13, may be an interesting strategy by which to inhibit TAM differentiation
      and, thus, their protumorigenic activities. In vitro inhibition of the Stat6
      pathway by using small interfering RNA or the pharmacologic inhibitor, AS1517499,
      inhibited the differentiation of mouse RAW264.7 macrophages into the M2
      phenotype, as demonstrated by the reduction of Arg-1 (arginase-1) and Mrc-1
      (mannose receptor 1) expression and arginase activity. In vivo, AS1517499
      significantly attenuated tumor growth and early liver metastasis in an orthotopic
      4T1 mammary carcinoma mouse model. Furthermore, in another experiment, we
      observed an increase in the intrahepatic mRNA expression of F4/80 (EGF-like
      module-containing mucin-like hormone receptor-like 1; total macrophages) and M2
      macrophage markers [ Ym-1 (chitinase 3-like protein 3) and Mrc-1] and metastatic
      niche markers [ Mmp-2 (matrix metalloproteinase-2), Postn (periostin), and Cd34]
      in mice with increasing growth of primary tumors. Of interest, these markers were
      found to be reduced after treatment with AS1517499. In summary, inhibition of the
      Stat6 pathway in TAMs is a vital therapeutic approach to attenuate tumor growth
      and metastasis by inhibiting TAM-induced protumorigenic and prometastatic
      activities.-Binnemars-Postma, K., Bansal, R., Storm, G., Prakash, J. Targeting
      the Stat6 pathway in tumor-associated macrophages reduces tumor growth and
      metastatic niche formation in breast cancer.

PMID- 29066615
TI  - Quality of provider-offered Medicare Advantage plans.

PMID- 29066616
TI  - Precommitting to choose wisely about low-value services: a stepped wedge cluster
      randomised trial.
AB  - BACKGROUND: Little is known about how to discourage clinicians from ordering low
      value services. Our objective was to test whether clinicians committing their
      future selves (ie, precommitting) to follow Choosing Wisely recommendations with
      decision supports could decrease potentially low-value orders. METHODS: We
      conducted a 12-month stepped wedge cluster randomised trial among 45 primary care
      physicians and advanced practice providers in six adult primary care clinics of a
      US community group practice.Clinicians were invited to precommit to Choosing
      Wisely recommendations against imaging for uncomplicated low back pain, imaging
      for uncomplicated headaches and unnecessary antibiotics for acute sinusitis.
      Clinicians who precommitted received 1-6 months of point-of-care precommitment
      reminders as well as patient education handouts and weekly emails with resources
      to support communication about low-value services.The primary outcome was the
      difference between control and intervention period percentages of visits with
      potentially low-value orders. Secondary outcomes were differences between control
      and intervention period percentages of visits with possible alternate orders, and
      differences between control and 3-month postintervention follow-up period
      percentages of visits with potentially low-value orders. RESULTS: The
      intervention was not associated with a change in the percentage of visits with
      potentially low-value orders overall, for headaches or for acute sinusitis, but
      was associated with a 1.7% overall increase in alternate orders (p=0.01). For low
      back pain, the intervention was associated with a 1.2% decrease in the percentage
      of visits with potentially low-value orders (p=0.001) and a 1.9% increase in the
      percentage of visits with alternate orders (p=0.007). No changes were sustained
      in follow-up. CONCLUSION: Clinician precommitment to follow Choosing Wisely
      recommendations was associated with a small, unsustained decrease in potentially
      low-value orders for only one of three targeted conditions and may have increased
      alternate orders. TRIAL REGISTRATION NUMBER: NCT02247050; Pre-results.

PMID- 29066617
TI  - A novel approach for data integration and disease subtyping.
AB  - Advances in high-throughput technologies allow for measurements of many types of
      omics data, yet the meaningful integration of several different data types
      remains a significant challenge. Another important and difficult problem is the
      discovery of molecular disease subtypes characterized by relevant clinical
      differences, such as survival. Here we present a novel approach, called
      perturbation clustering for data integration and disease subtyping (PINS), which
      is able to address both challenges. The framework has been validated on thousands
      of cancer samples, using gene expression, DNA methylation, noncoding microRNA,
      and copy number variation data available from the Gene Expression Omnibus, the
      Broad Institute, The Cancer Genome Atlas (TCGA), and the European Genome-Phenome
      Archive. This simultaneous subtyping approach accurately identifies known cancer
      subtypes and novel subgroups of patients with significantly different survival
      profiles. The results were obtained from genome-scale molecular data without any
      other type of prior knowledge. The approach is sufficiently general to replace
      existing unsupervised clustering approaches outside the scope of bio-medical
      research, with the additional ability to integrate multiple types of data.

PMID- 29066618
TI  - Epigenetic modification of miR-663 controls mitochondria-to-nucleus retrograde
      signaling and tumor progression.
AB  - The normal cellular function requires communication between mitochondria and the
      nucleus, termed mitochondria-to-nucleus retrograde signaling. Disruption of this
      mechanism has been implicated in the development of cancers. Many proteins are
      known modulators of retrograde signaling, but whether microRNAs (miRNAs) are also
      involved is unknown. We conducted an miRNA microarray analysis using RNA from a
      parental cell line, a Rho0 line lacking mitochondrial DNA (mtDNA) and a Rho0 line
      with restored mtDNA. We found that miR-663 was down-regulated in the mtDNA
      depleted Rho0 line. mtDNA restoration reversed this miRNA to parental level,
      suggesting that miR-663 may be epigenetically regulated by retrograde signaling.
      By using methylation-specific PCR and bisulfite sequencing we demonstrate that
      miR-663 promoter is epigenetically regulated not only by genetic but also by
      pharmacological disruption of oxidative phosphorylation (OXPHOS). Restoration of
      OXPHOS Complex I inhibitor-induced miR-663 expression by N-acetylcysteine
      suggested that reactive oxygen species (ROS) play a key role in epigenetic
      regulation of miR-663. We determined that miR-663 regulates the expression of
      nuclear-encoded respiratory chain subunits involved in Complexes I, II, III, and
      IV. miR-663 also controlled the expression of the Complexes I (NDUFAF1), II
      (SDHAF2), III (UQCC2), and IV (SCO1) assembly factors and was required for
      stability of respiratory supercomplexes. Furthermore, using luciferase assays, we
      found that miR-663 directly regulates UQCC2. The anti-miR-663 reduced OXPHOS
      complex activity and increased in vitro cellular proliferation and promoted tumor
      development in vivo in mice. We also found that increased miR-663 expression in
      breast tumors consistently correlates with increased patient survival. We provide
      the first evidence for miRNA controlling retrograde signaling, demonstrating its
      epigenetic regulation and its role in breast tumorigenesis.

PMID- 29066619
TI  - Dissecting the role of conformational change and membrane binding by the
      bacterial cell division regulator MinE in the stimulation of MinD ATPase
      activity.
AB  - The bacterial cell division regulators MinD and MinE together with the division
      inhibitor MinC localize to the membrane in concentrated zones undergoing
      coordinated pole-to-pole oscillation to help ensure that the cytokinetic division
      septum forms only at the mid-cell position. This dynamic localization is driven
      by MinD-catalyzed ATP hydrolysis, stimulated by interactions with MinE's anti
      MinCD domain. This domain is buried in the 6-beta-stranded MinE "closed"
      structure, but is liberated for interactions with MinD, giving rise to a 4-beta
      stranded "open" structure through an unknown mechanism. Here we show that MinE
      membrane interactions induce a structural change into a state resembling the open
      conformation. However, MinE mutants lacking the MinE membrane-targeting sequence
      stimulated higher ATP hydrolysis rates than the full-length protein, indicating
      that binding to MinD is sufficient to trigger this conformational transition in
      MinE. In contrast, conformational change between the open and closed states did
      not affect stimulation of ATP hydrolysis rates in the absence of membrane
      binding, although the MinD-binding residue Ile-25 is critical for this
      conformational transition. We therefore propose an updated model where MinE is
      brought to the membrane through interactions with MinD. After stimulation of ATP
      hydrolysis, MinE remains bound to the membrane in a state that does not catalyze
      additional rounds of ATP hydrolysis. Although the molecular basis for this
      inhibited state is unknown, previous observations of higher-order MinE self
      association may explain this inhibition. Overall, our findings have general
      implications for Min protein oscillation cycles, including those that regulate
      cell division in bacterial pathogens.

PMID- 29066620
TI  - Autoantibodies against the cell surface-associated chaperone GRP78 stimulate
      tumor growth via tissue factor.
AB  - Tumor cells display on their surface several molecular chaperones that normally
      reside in the endoplasmic reticulum. Because this display is unique to cancer
      cells, these chaperones are attractive targets for drug development. Previous
      epitope-mapping of autoantibodies (AutoAbs) from prostate cancer patients
      identified the 78-kDa glucose-regulated protein (GRP78) as one such target.
      Although we previously showed that anti-GRP78 AutoAbs increase tissue factor (TF)
      procoagulant activity on the surface of tumor cells, the direct effect of TF
      activation on tumor growth was not examined. In this study, we explore the
      interplay between the AutoAbs against cell surface-associated GRP78, TF
      expression/activity, and prostate cancer progression. First, we show that tumor
      GRP78 expression correlates with disease stage and that anti-GRP78 AutoAb levels
      parallel prostate-specific antigen concentrations in patient-derived serum
      samples. Second, we demonstrate that these anti-GRP78 AutoAbs target cell-surface
      GRP78, activating the unfolded protein response and inducing tumor cell
      proliferation through a TF-dependent mechanism, a specific effect reversed by
      neutralization or immunodepletion of the AutoAb pool. Finally, these AutoAbs
      enhance tumor growth in mice bearing human prostate cancer xenografts, and
      heparin derivatives specifically abrogate this effect by blocking AutoAb binding
      to cell-surface GRP78 and decreasing TF expression/activity. Together, these
      results establish a molecular mechanism in which AutoAbs against cell-surface
      GRP78 drive TF-mediated tumor progression in an experimental model of prostate
      cancer. Heparin derivatives counteract this mechanism and, as such, represent
      potentially appealing compounds to be evaluated in well-designed translational
      clinical trials.

PMID- 29066621
TI  - A conserved tryptophan within the WRDPLVDID domain of yeast Pah1 phosphatidate
      phosphatase is required for its in vivo function in lipid metabolism.
AB  - PAH1-encoded phosphatidate phosphatase, which catalyzes the dephosphorylation of
      phosphatidate to produce diacylglycerol at the endoplasmic reticulum membrane,
      plays a major role in controlling the utilization of phosphatidate for the
      synthesis of triacylglycerol or membrane phospholipids. The conserved N-LIP and
      haloacid dehalogenase-like domains of Pah1 are required for phosphatidate
      phosphatase activity and the in vivo function of the enzyme. Its non-conserved
      regions, which are located between the conserved domains and at the C terminus,
      contain sites for phosphorylation by multiple protein kinases. Truncation
      analyses of the non-conserved regions showed that they are not essential for the
      catalytic activity of Pah1 and its physiological functions (e.g. triacylglycerol
      synthesis). This analysis also revealed that the C-terminal region contains a
      previously unrecognized WRDPLVDID domain (residues 637-645) that is conserved in
      yeast, mice, and humans. The deletion of this domain had no effect on the
      catalytic activity of Pah1 but caused the loss of its in vivo function. Site
      specific mutational analyses of the conserved residues within WRDPLVDID indicated
      that Trp-637 plays a crucial role in Pah1 function. This work also demonstrated
      that the catalytic activity of Pah1 is required but is not sufficient for its in
      vivo functions.

PMID- 29066622
TI  - MicroRNA-155 induction via TNF-alpha and IFN-gamma suppresses expression of
      programmed death ligand-1 (PD-L1) in human primary cells.
AB  - Programmed death ligand-1 (PD-L1) is a critical regulator of T cell function
      contributing to peripheral immune tolerance. Although it has been shown that
      posttranscriptional regulatory mechanisms control PD-L1 expression in cancer, it
      remains unknown whether such regulatory loops operate also in non-transformed
      cells. Here we studied PD-L1 expression in human dermal lymphatic endothelial
      cells (HDLECs), which play key roles in immunity and cancer. Treatment of HDLECs
      with the pro-inflammatory cytokines IFN-gamma and TNF-alpha synergistically up
      regulated PD-L1 expression. IFN-gamma and TNF-alpha also affected expression of
      several microRNAs (miRNAs) that have the potential to suppress PD-L1 expression.
      The most highly up-regulated miRNA following IFN-gamma and TNF-alpha treatment in
      HDLECs was miR-155, which has a central role in the immune system and cancer.
      Induction of miR-155 was driven by TNF-alpha, the effect of which was
      significantly enhanced by IFN-gamma. The PD-L1 3'-UTR contains two functional miR
      155-binding sites. Endogenous miR-155 controlled the kinetics and maximal levels
      of PD-L1 induction upon IFN-gamma and TNF-alpha treatments. We obtained similar
      findings in dermal fibroblasts, demonstrating that the IFN-gamma/TNF-alpha/miR
      155/PD-L1 pathway is not restricted to HDLECs. These results reveal miR-155 as a
      critical component of an inflammation-induced regulatory loop controlling PD-L1
      expression in primary cells.

PMID- 29066624
TI  - Active site-adjacent phosphorylation at Tyr-397 by c-Abl kinase inactivates
      caspase-9.
AB  - Caspase-9 (casp-9) is an initiator caspase and plays a central role in activating
      apoptotic cell death. Control of all caspases is tightly regulated by a series of
      phosphorylation events enacted by several different kinases. Caspase-9 is the
      most heavily phosphorylated of all caspases, with phosphorylation of at least 11
      distinct residues in all three caspase-9 domains by nine kinases. Caspase-9
      phosphorylation by the non-receptor tyrosine kinase c-Abl at Tyr-153 reportedly
      leads to caspase-9 activation. All other phosphorylation events on caspases have
      been shown to block proteolytic function by a number of mechanisms, so we sought
      to unravel the molecular mechanism of the putative caspase-9 activation by
      phosphorylation. Surprisingly, we observed no evidence for Tyr-153
      phosphorylation of caspase-9 in vitro or in cells, suggesting that Tyr-153 is not
      phosphorylated by c-Abl. Instead, we identified a new site for c-Abl-mediated
      phosphorylation, Tyr-397. This residue is adjacent to the caspase-9 active site
      but, as a member of the second shell, not a residue that directly contacts
      substrate. Our results further indicate that Tyr-397 is the dominant site of c
      Abl phosphorylation both in vitro and upon c-Abl activation in cells. Of note,
      phosphorylation at this site inhibits caspase-9 activity, and the bulk of the
      added phosphate moiety appeared to directly block substrate binding. c-Abl plays
      both proapoptotic and prosurvival roles, and our findings suggest that c-Abl's
      effects on caspase-9 activity promote the prosurvival mode.

PMID- 29066626
TI  - Hookworm: a neglected resurgent infection.

PMID- 29066623
TI  - Reconciling contradictory findings: Glucose transporter 1 (GLUT1) functions as an
      oligomer of allosteric, alternating access transporters.
AB  - Recent structural studies suggest that GLUT1 (glucose transporter 1)-mediated
      sugar transport is mediated by an alternating access transporter that
      successively presents exofacial (e2) and endofacial (e1) substrate-binding sites.
      Transport studies, however, indicate multiple, interacting (allosteric), and co
      existent, exo- and endofacial GLUT1 ligand-binding sites. The present study asks
      whether these contradictory conclusions result from systematic analytical error
      or reveal a more fundamental relationship between transporter structure and
      function. Here, homology modeling supported the alternating access transporter
      model for sugar transport by confirming at least four GLUT1 conformations, the so
      called outward, outward-occluded, inward-occluded, and inward GLUT1
      conformations. Results from docking analysis suggested that outward and outward
      occluded conformations present multiple beta-d-glucose and maltose interaction
      sites, whereas inward-occluded and inward conformations present only a single
      beta-d-glucose interaction site. Gln-282 contributed to sugar binding in all
      GLUT1 conformations via hydrogen bonding. Mutating Gln-282 to alanine (Q282A)
      doubled the Km(app) for 2-deoxy-d-glucose uptake and eliminated cis-allostery
      (stimulation of sugar uptake by subsaturating extracellular maltose) but not
      trans-allostery (uptake stimulation by subsaturating cytochalasin B). cis
      Allostery persisted, but trans-allostery was lost in an oligomerization-deficient
      GLUT1 variant in which we substituted membrane helix 9 with the equivalent GLUT3
      sequence. Moreover, Q282A eliminated cis-allostery in the oligomerization
      variant. These findings reconcile contradictory conclusions from structural and
      transport studies by suggesting that GLUT1 is an oligomer of allosteric,
      alternating access transporters in which 1) cis-allostery is mediated by
      intrasubunit interactions and 2) trans-allostery requires intersubunit
      interactions.

PMID- 29066627
TI  - Detection of Neisseria gonorrhoeae and Chlamydia trachomatis from pooled rectal,
      pharyngeal and urine specimens in men who have sex with men.
AB  - OBJECTIVES: Screening of men who have sex with men (MSM) for Chlamydia
      trachomatis (CT) and Neisseria gonorrhoeae (NG) requires sampling from anorectal
      and pharyngeal sites in addition to urogenital sampling. Due to the cost of
      testing multiple anatomical sites individually testing of pooled specimens has
      potential merit. The Cepheid GeneXpert CT/NG assay (GeneXpert), which also has
      potential for point-of-care nucleic acid testing in the sexual health clinic, has
      not been assessed for pooled specimen testing. METHODS: We prospectively compared
      GeneXpert testing of pooled pharyngeal and rectal swabs with urine samples to
      standard of care testing of individual specimens from 107 participants using the
      Roche cobas 4800 CT/NG assay (cobas) for CT and NG in high-risk MSM attending an
      inner city sexual health clinic. RESULTS: We found testing of pooled pharyngeal,
      rectal and urine samples by the GeneXpert to have 100% agreement for NG and 94%
      overall agreement for CT when compared with individual specimen testing by cobas.
      For CT testing, 14 cases were detected for both tests, 4for cobas only, 2 for
      GeneXpert only and 89 participants were negative for both tests. CONCLUSIONS:
      Pooled specimen CT and NG testing by the GeneXpert was accurate when compared
      with single specimen testing and has potential for screening MSM for CT and NG.
      The role of pooled specimen testing with the GeneXpert as a point-of-care nucleic
      acid test in MSM requires further investigation.

PMID- 29066628
TI  - Treatment of chlamydia and gonorrhoea, compliance with treatment guidelines and
      factors associatedwith non-compliant prescribing: findings form a cross-sectional
      study.
AB  - OBJECTIVES: Proper antibiotic treatment of STI reduces transmission,
      antimicrobial resistance and serious disease complications. In this study, we
      assessed compliance with STI treatment guidelines for genital gonorrhoea and
      chlamydia infections in Estonia. METHODS: Prescription data from the Estonian
      Health Insurance Fund on 7556 treatment episodes of 6499 patients treated for
      gonorrhoea or chlamydia during 2012-2014 were analysed to assess compliance with
      the guidelines and factors associated with it. RESULTS: Between 1 January 2012
      and 31 December 2014, a total of 6074 patients were treated for chlamydia and 425
      for gonorrhoea in Estonia. Among all prescriptions, 48.6% were non-compliant with
      gonorrhoea treatment guidelines and 3.8% for chlamydia. Non-compliant antibiotic
      treatment for gonorrhoea was associated with patient gender (female (adjusted OR
      (AOR)) 3.0, 95% CI 1.6 to 5.9), region (east AOR 3.3, 95% CI 1.3 to 8.2; west AOR
      6.5, 95% CI 2.2 to 19.7) and prescribing physician specialty (general healthcare
      doctors: AOR 5.6, 95% CI 2.3 to 13.8; gynaecologists: AOR 5.9, 95% CI 2.8 to
      12.4). Non-compliant antibiotic treatment for chlamydia was associated with
      younger patient age (15-24 AOR 0.5, 95% CI 0.4 to 0.7), region (north AOR 1.9,
      95% CI 1.4 to 2.6; west AOR 2.3, 95% CI 1.5 to 3.4) and multiple treatment
      episodes (AOR 2.7, 95% CI 2.1 to 3.9). Approximately 14% of prescriptions were
      multiple treatments for the same patient for the same infection over the 3-year
      period (6.1% for gonorrhoea and 14.5% for chlamydia). CONCLUSION: There are
      significant differences in terms of compliance with treatment guidelines for
      gonorrhoea and chlamydia, and several factors associated with non-compliance that
      can potentially be targeted with interventions. Future research should explore
      reasons clinicians do not follow guidelines and examine ways to improve practice
      among doctors and patients and assess factors associated with multiple
      treatments, particularly multiple treatments for the same STI.

PMID- 29066629
TI  - Perceived intentional transmission of HIV infection, sustained viral suppression
      and psychosocial outcomes among men who have sex with men living with HIV: a
      cross-sectional assessment.
AB  - OBJECTIVE: HIV continues to be a global and national public health challenge, and
      men who have sex with men (MSM) are disproportionately affected in the USA.
      Transmission of HIV is intentional if the person living with HIV knows about
      his/her serostatus, acts with the intention to and actually transmits HIV.
      Research on intentional transmission of HIV infections is lacking, and the
      relationships between perceived intentional transmission, viral suppression and
      psychosocial outcomes have not been assessed. The objective of this study was to
      investigate the association between perceived intentional transmission of HIV,
      sustained viral suppression and psychosocial outcomes. METHODS: Data were
      obtained from 338 MSM living with HIV who participated in a disclosure
      intervention study. Logistic and linear regression models were used to assess the
      associations between perceived intentional transmission and viral suppression,
      condomless anal intercourse in the past 30 days, being at risk for clinical
      depression, substance use, self-efficacies for condom use, HIV disclosure and
      negotiation of safer sex practices, and sexual compulsivity. RESULTS: 44% of the
      study population reported perceiving intentional HIV transmission. After
      adjusting for sociodemographic characteristics, men who thought that they were
      infected intentionally had 69% higher odds (adjusted OR: 1.69; 95% CI 1.01 to
      2.83) of being at risk for clinical depression, and on average, scored
      approximately 3 points and 4 points higher on depressive symptoms and sexual
      compulsivity, respectively (adjusted beta: 3.29; 95% CI 0.42 to 6.15; adjusted
      beta: 3.74; 95% CI 1.32 to 6.17) compared with men who did not think that they
      were intentionally infected. After adjusting for confounders, there was no
      statistically significant association between perceived intentional transmission
      and viral suppression. CONCLUSIONS: Intervention programmes for MSM living with
      HIV who thought they were infected intentionally are warranted and should aim to
      attenuate depressive symptoms and sexual compulsivity.

PMID- 29066625
TI  - Local energetic frustration affects the dependence of green fluorescent protein
      folding on the chaperonin GroEL.
AB  - The GroE chaperonin system in Escherichia coli comprises GroEL and GroES and
      facilitates ATP-dependent protein folding in vivo and in vitro Proteins with very
      similar sequences and structures can differ in their dependence on GroEL for
      efficient folding. One potential but unverified source for GroEL dependence is
      frustration, wherein not all interactions in the native state are optimized
      energetically, thereby potentiating slow folding and misfolding. Here, we chose
      enhanced green fluorescent protein as a model system and subjected it to random
      mutagenesis, followed by screening for variants whose in vivo folding displays
      increased or decreased GroEL dependence. We confirmed the altered GroEL
      dependence of these variants with in vitro folding assays. Strikingly, mutations
      at positions predicted to be highly frustrated were found to correlate with
      decreased GroEL dependence. Conversely, mutations at positions with low
      frustration were found to correlate with increased GroEL dependence. Further
      support for this finding was obtained by showing that folding of an enhanced
      green fluorescent protein variant designed computationally to have reduced
      frustration is indeed less GroEL-dependent. Our results indicate that changes in
      local frustration also affect partitioning in vivo between spontaneous and
      chaperonin-mediated folding. Hence, the design of minimally frustrated sequences
      can reduce chaperonin dependence and improve protein expression levels.

PMID- 29066631
TI  - Advancing a High Throughput Glycotope-centric Glycomics Workflow Based on nanoLC
      MS2-product Dependent-MS3 Analysis of Permethylated Glycans.
AB  - The intrinsic nature of glycosylation, namely nontemplate encoded, stepwise
      elongation and termination with a diverse range of isomeric glyco-epitopes
      (glycotopes), translates into ambiguity in most cases of mass spectrometry (MS)
      based glycomic mapping. It is arguable that whether one needs to delineate every
      single glycomic entity, which may be counterproductive. Instead, one should focus
      on identifying as many structural features as possible that would collectively
      define the glycomic characteristics of a cell or tissue, and how these may change
      in response to self-programmed development, immuno-activation, and malignant
      transformation. We have been pursuing this line of analytical strategy that homes
      in on identifying the terminal sulfo-, sialyl, and/or fucosylated glycotopes by
      comprehensive nanoLC-MS2-product dependent MS3 analysis of permethylated glycans,
      in conjunction with development of a data mining computational tool, GlyPick, to
      enable an automated, high throughput, semi-quantitative glycotope-centric
      glycomic mapping amenable to even nonexperts. We demonstrate in this work that
      diagnostic MS2 ions can be relied on to inform the presence of specific
      glycotopes, whereas their possible isomeric identities can be resolved at MS3
      level. Both MS2 and associated MS3 data can be acquired exhaustively and
      processed automatically by GlyPick. The high acquisition speed, resolution, and
      mass accuracy afforded by top-notch Orbitrap Fusion MS system now allow a
      sensible spectral count and/or summed ion intensity-based glycome-wide glycotope
      quantification. We report here the technical aspects, reproducibility and
      optimization of such an analytical approach that uses the same acidic reverse
      phase C18 nanoLC conditions fully compatible with proteomic analysis to allow
      rapid hassle-free switching. We further show how this workflow is particularly
      effective when applied to larger, multiply sialylated and fucosylated N-glycans
      derived from mouse brain. The complexity of their terminal glycotopes including
      variants of fucosylated and disialylated type 1 and 2 chains would otherwise not
      be adequately delineated by any conventional LC-MS/MS analysis.

PMID- 29066630
TI  - Population-based Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas
      vaginalis prevalence using discarded, deidentified urine specimens previously
      collected for drug testing.

PMID- 29066632
TI  - Lymphatic malformation with acquired Horner syndrome in an infant.
AB  - An infantpresented with right upper eyelid ptosis and was subsequently diagnosed
      with acquired Horner syndrome. Further evaluation revealed a right-sided
      cervicothoracic lymphatic malformation. At 13 weeks of age, the child underwent
      percutaneous intracystic sclerotherapy with a mixture of sodium tetradecyl
      sulphate and ethanol. Twenty-one weeks after initial treatment, ophthalmic
      examination showed complete resolution of the blepharoptosis and pupillary
      miosis. Percutaneous sclerotherapy not only effectively treated the space
      occupying lymphatic malformation but also reversed the Horner syndrome that was
      presumably induced by neural tension (more likely) or compression.

PMID- 29066633
TI  - Leiomyosarcoma presenting as 'idiopathic' unilateral lower limb lymphoedema.
AB  - A 74-year-old woman presented with an 8-year history of unilateral swelling of
      her right lower limb, which was thought to be 'idiopathic' lymphoedema until she
      noticed a painless swelling in her right groin. Physical examination showed a
      painless, non-pulsatile, deep-seated mass in her right proximal thigh with
      significant lymphoedema distally. MRI scan showed a large mass at her right
      inguinal region, involving the common femoral vein. Histological examination on
      complete excision revealed leiomyosarcoma. It is important to exclude proximal
      obstructive lesion before making a diagnosis of unilateral idiopathic lower limb
      lymphoedema.

PMID- 29066634
TI  - Rhomboencephalosynapsis.

PMID- 29066635
TI  - Measurement of bone mineral density as an efficacy marker in denosumab treatment
      of giant cell tumour of bone.
AB  - Three patients with giant cell tumour of bone (GCTB) in the lower extremity,
      where the only surgical treatment options were amputation or severe weakening of
      the bone, were treated with denosumab (D-mab) to strengthen the bone mass in the
      tumour. In order to quantify changes in bone mineral density (BMD) in the GCTB
      lesion during D-mab treatment, we did repeated dual-energy X-ray absorptiometry
      (DXA) scans. The patients underwent operation after 3, 4 and 8 months of D-mab
      treatment, respectively. The tumours in all three patients responded markedly to
      D-mab, and up to 50% BMD increase was observed. There was almost no BMD change in
      the control scans in the hip and spine of the same patients. DXA scans provide no
      information about local tumour response, but may be of value in evaluation of the
      time and size of the D-mab response in GCTB, and thereby aid in finding the best
      timing for surgery.

PMID- 29066636
TI  - Giant mediastinal parathyroid adenoma presenting as bilateral brown tumour of
      mandible: a rare presentation of primary hyperparathyroidism.
AB  - Hyperparathyroidism (HPT) is becoming increasingly common endocrinopathy in
      clinical practice. Nowadays, it is mostly diagnosed in subclinical or early
      clinical stage. Bony involvement in HPT has seen significant fall in incidence.
      Brown tumour of bone is exceptionally rare as a first manifestation of primary
      HPT (PHPT). Its radiological and histopathological features may be mistaken for
      other bony pathologies. If possibility of underlying HPT is overlooked the
      disease is bound to recur after surgery adding to morbidity of the patient. Here
      we present a case of bilateral brown tumour of mandible which was mistakenly
      treated as giant cell granuloma by surgical curettage. That the patient was
      harbouring an ectopic parathyroid adenoma with hypercalcemia causing non-specific
      symptoms was missed by the referring physician. This led to recurrence of the
      lesion. On subsequent evaluation, a giant mediastinal parathyroid adenoma causing
      PHPT was detected at our centre and was removed via mini sternotomy approach.

PMID- 29066638
TI  - Birt-Hogg-Dube syndrome: awareness is important!
AB  - Birt-Hogg-Dube (BHD) is a rare syndrome of inherited renal cell carcinomas,
      characterised by cutaneous lesions and pulmonary cysts and pneumothorax in a vast
      majority of the patients. Awareness of this syndrome is important in order to
      refer patients for genetic counselling and personalised follow-up as soon as
      possible. We describe a case of a 30-year-old female referred to our institution
      due to incidental discovery of solid bilateral renal masses. Renal biopsies were
      consistent with chromophobe tumour, and bilateral nephrectomy was performed.
      Gross examination revealed deformed kidneys with 28 brown and solid lesions, size
      variable between 0.1 and 6 cm, histologically corresponding to renal cell
      carcinomas, chromophobe type. Genetic test was required that showed a
      c.573delGAinsT frameshift mutation in heterozigosity at the folliculin gene,
      consistent with BHD diagnosis.

PMID- 29066637
TI  - Transcatheter valve implantation to inferior vena cava to control carcinoid
      symptoms.
AB  - Severe carcinoid syndrome and carcinoid heart disease in neuroendocrine tumours
      can have a significant impact on a patient's quality of life and are a major
      cause of morbidity and mortality. We present a novel approach to managing a
      patient with medically uncontrollable carcinoid syndrome. Inferior and superior
      vena cava placement of transcatheter heart valves has been used to treat patients
      with right heart failure due to severe tricuspid and pulmonary regurgitation.
      However, this procedure has not been attempted to specifically reduce hormone
      secretion, primarily from the liver, in order to control carcinoid syndrome
      symptoms. We attempted this procedure in a patient with severe carcinoid disease
      and tricuspid regurgitation as a bridge to later definitive therapy. The
      procedure was technically successful, but did not improve carcinoid symptoms. The
      possible reasons for the failure are discussed here.

PMID- 29066639
TI  - Idiopathic catastrophic thrombosis with happy ending.
AB  - A 59-year-old male patient suffered three life-threatening instent thromboses
      after an initial resuscitation due to an ST-segment elevation myocardial
      infarction of the anterior cardiac wall. With a high-risk profile for heparin
      induced thrombocytopenia (HIT), he was placed on argatroban after the second
      reinfarction. Under this apparently appropriate treatment, a third reinfarction
      occurred, and the patient had to undergo high-risk cardiac bypass surgery. Later
      on, a deep vein thrombosis and an intracardiac thrombus formed. Despite a
      positive screening test for HIT and a single positive result in the heparin
      induced platelet aggregation test, we are not convinced that HIT was the only
      underlying cause for this 'catastrophic thrombotic syndrome'. We speculate that a
      massive generation of thrombin, reflected in consistently high D dimers and the
      need of copious amounts of a direct thrombin inhibitor, triggered the set of
      events. With this case report, we want to raise awareness for cardiac
      complications in patients with complex clotting disorders and share our
      experience in the diagnostic and therapeutic management of such an unusual
      scenario.

PMID- 29066640
TI  - Neuroendocrine tumour in pancreatic dorsal agenesis: a rare association.
AB  - Pancreatic dorsal agenesis (PDA) is a rare congenital anomaly, usually
      asymptomatic, that can present with abdominal pain, pancreatitis, diabetes
      mellitus and jaundice. Pancreatic tumours in PDA background are extremely rare,
      and when they occur are mainly pancreatic ductal adenocarcinoma. We present a
      case of a 48-year-old female patient with incidental detection of a 26*20 mm
      nodular lesion of the cephalic pancreas on ultrasound. Surgery was performed and
      gross examination revealed PDA with a tumour developed around the Wirsung duct.
      Histology showed a neuroendocrine tumour G1 with neural and vascular invasion.
      Two and half years later, the patient is alive and without tumour relapse.
      Awareness of the association of PDA and pancreatic tumours is fundamental in
      order to develop personalised follow-up programmes.

PMID- 29066641
TI  - Adverse reaction with suvorexant for insomnia: acute worsening of depression with
      emergence of suicidal thoughts.
AB  - A 59-year-old woman on daily peritoneal dialysis for end-stage renal failure
      received care at an outpatient psychiatric clinic for her diagnoses that include
      major depressive disorder, generalised anxiety disorder and insomnia disorder.
      Although there was partial improvement in the patient's mood and anxiety symptoms
      with antidepressant treatment, insomnia remained a persistent complaint despite
      adequate trials of different sleep medications. The novel hypnotic, suvorexant
      (Belsomra, Merck & Co.) was then initiated at the recommended bedtime dose of 10
      mg and was followed by a 15 mg dose the following night. Within an hour after
      taking her second suvorexant dose, the severity of patient's depression symptoms
      worsened and was accompanied by new onset of suicidal thoughts.

PMID- 29066642
TI  - Case of tumoral calcinosis on images: a rare clinicopathological entity.

PMID- 29066643
TI  - Metastatic meningioma: a rare cause of mediastinal lymphadenopathy.

PMID- 29066644
TI  - Olfactory nerve hypertrophy: a clue to the presence of ipsilateral
      megalencephaly.

PMID- 29066645
TI  - Necrotising pneumonia following influenza due to PVL-negative Staphylococcus
      aureus in a 64-year-old woman.

PMID- 29066646
TI  - Recurrence of immature ovarian teratoma as malignant follicular carcinoma with
      liver and peritoneal metastasis 22 years after completion of initial treatment.
AB  - Growing tumour syndrome (GTS) is a rare event in which germ cell tumours treated
      with chemotherapy undergo maturation, acquire resistance to chemotherapy and
      regrow. The optimum treatment strategy is complete surgical excision. We report
      on a case of GTS with malignant metastases to the liver presenting 22 years after
      completion of treatment for immature teratoma, successfully managed with surgical
      resection alone.

PMID- 29066647
TI  - Buttock wounds: beware what lies beneath.
AB  - A 25-year-old man presented to a major trauma centre with multiple stab wounds,
      most significantly to the right buttock. Triple-phase CT revealed no acute
      bleeding and his wounds were closed. In the month following injury, he re
      presented seven times to the emergency department (ED) complaining of bleeding
      and wound breakdown. After his seventh ED attendance, he was examined under
      general anaesthesia. Intraoperatively, profuse arterial bleeding was encountered
      and the local major haemorrhage protocol was activated. The on-call consultant
      vascular surgeon attended and definitive control was achieved. A large haematoma
      had acted to tamponade ongoing arterial bleeding and an underlying
      pseudoaneurysm: a finding not reported, but present, on the initial CT angiogram.
      Following 24 hours in the intensive care unit, he was transferred to the surgical
      ward and discharged 4 days later. Regular review in the outpatient department
      over the following 9 weeks monitored successful wound healing.

PMID- 29066648
TI  - Vascular consideration in repair of total scalp avulsion.
AB  - Successful total scalp replantation was performed in our case. Based on the
      angiosome concept and anatomical study, the avulsed scalp survived with
      unilateral anastomosis of the superficial temporal artery and superficial
      temporal vein, largely due to the presence of rich arterial and venous arcades in
      the scalp. The patient currently has no problems with activities of daily living,
      although total hypoaesthesia and dysfunction of the left frontal muscle of the
      forehead are present. In addition, the combined findings of hair growth pattern
      indicated the vascular territories of the scalp skin.

PMID- 29066650
TI  - Subarachnoidal fat droplet deposition and fat embolism syndrome.

PMID- 29066649
TI  - Urothelial carcinoma in an orthotopic neobladder: an unusual pattern of
      recurrence and metastasis.
AB  - We report a case of a 65-year-old patient with muscle invasive bladder cancer
      that was treated with neoadjuvant chemotherapy, followed by radical
      cystoprostatectomy with pelvic lymph node dissection and orthotopic neobladder
      according to Hautmann. Nine years later, routine follow-up showed local
      recurrence in the neobladder and metastatic disease of the urothelial carcinoma
      in the related mesenteric lymph nodes. The entire neobladder specimen was removed
      including the mesentery of the neobladder. Based on the anatomical lymph drainage
      of the ileal neobladder, we considered the metastatic disease in the mesentery
      lymph node as locoregional disease spread. This case shows that such locoregional
      lymph node metastasis may be amenable to treatment by induction chemotherapy and
      radical surgery.

PMID- 29066651
TI  - Rescuing the host Descemet's membrane in full-thickness traumatic wound
      dehiscence in deep anterior lamellar keratoplasty: intraoperative optical
      coherence tomography (iOCT)-guided technique.
AB  - Optimal visual recovery following full-thickness traumatic wound dehiscence in a
      case of operated deep anterior lamellar keratoplasty (DALK) is rarely seen. Here
      we report a case of 22-year-old male patient presented to our casualty department
      with complaint of sudden-onset diminution of vision in his right eye following
      blunt trauma of 1 day duration. DALK had been performed 11 months ago for
      advanced keratoconus in the same eye. Best-corrected visual acuity (BCVA) in the
      right eye was hand movement close to face with accurate projection of rays and in
      the left eye was 20/20. Slit-lamp examination showed the presence of inferior 180
      degrees  graft dehiscence with broken sutures and shallow anterior chamber with
      corneal oedema. Repair of the dehiscence with descemetopexy was done under the
      guidance of intraoperative optical coherence tomography with the successful
      rescuing of the host Descemet's membrane. BCVA at 6 months follow-up was 20/40.

PMID- 29066652
TI  - Mucoepidermoid carcinoma of the posterior-lateral border of tongue: a rare
      presentation.
AB  - Mucoepidermoid carcinoma (MEC) is the most common malignant tumour of the major
      and minor salivary glands. Minor salivary glands are scattered in different areas
      of the oral cavity such as palate, retromolar area, floor of the mouth, buccal
      mucosa, lips and tongue, but so far, only a few lingual MEC cases have been
      documented in the literature and most of the studies have shown a predilection
      for base and dorsum of the tongue. We report a rare case of MEC involving the
      posterior-lateral border of the tongue.

PMID- 29066653
TI  - Use of i-gel for laser ablation of a bronchial lesion.
AB  - The use of laser for airway lesions requires airway management. Usual options
      include special laser-resistant endotracheal tubes. The use of supraglottic
      devices have been described in the literature. Laryngeal mask airway carries the
      risk of cuff damage during the use of laser. i-gel is made of thermoplastic
      material and does not require air inflation and thus potentially reduce the risk
      of cuff rupture. i-gel use in laser surgeries has not been described in the
      literature. We present successful airway management in laser surgery for
      bronchial tumour using i-gel.

PMID- 29066654
TI  - A newer technique of suture placement in scalpel and laser-assisted vestibular
      deepening.
AB  - Surgical vestibular deepening procedures are well established and are being
      routinely performed.In spite of being an old technique, postoperative results in
      most of the instances are disappointing. Usually eventual loss of the clinically
      gained vestibular depth obtained through the surgical procedures occurs. This
      happens mainly due to rapid epithelialisation of the surgical wound and healing
      by scarring. Therefore, in the present case, after the initial incision, the
      labial free end of flap was sutured by a new technique so as to prevent rapid
      epithelialisation. Finally, the incision was completed and vestibular deepening
      was achieved with the help of diode laser as they are reported to produce
      remarkably less scarring at the surgical site.

PMID- 29066655
TI  - Acute hepatitis B virus infection and severe non-immune haemolytic anaemia: a
      rare relationship.
AB  - The clinical presentation of acute hepatitis B virus (HBV) infection is usually
      related to the onset of liver failure and damage. Anaemia may occur, but it is
      only rarely attributed to haemolysis. The authors report about the case of a 41
      year-old woman with the diagnosis of acute HBV infection and coagulopathy
      (without encephalopathy) who developed non-immune haemolytic anaemia. Total
      recovery of the analytical liver profile, coagulopathy and anaemia was achieved
      through treatment targeting HBV.This case shows that, although rare, non-immune
      haemolytic anaemia may occur in association with acute HBV infection and that HBV
      suppression seems to lead to progressive anaemia resolution.

PMID- 29066656
TI  - Successful management of caesarean scar live ectopic pregnancies with local KCL
      and systemic methotrexate.
AB  - Two cases of live caesarean scar ectopic pregnancies are presented. Beta human
      chorionic gonadotropin (b-hCG) values in both patients at presentation were 50
      099 mIU and 297 969 mIU, respectively. Both were managed with intrasac potassium
      chloride injection to induce fetal demise and multiple dose methotrexate therapy.
      The time for b-hCG to become negative in both patients was 91 days and 119 days,
      respectively. Successful management of live caesarean scar pregnancies even with
      very high b-hCG is possible with minimally invasive approach.

PMID- 29066657
TI  - Case of undiagnosed pneumocystis pneumonia (PCP).
AB  - Pneumocystis pneumonia (PCP) is an opportunistic fungal infection that is usually
      seen in immunocompromised patients, especially those with HIV, malignancies,
      organ transplants and on drug therapies like chemotherapy and steroids. PCP has
      subacute presentation in patients with AIDS which if left untreated gets worse
      and is a significant cause of morbidity and mortality. Here we present a case of
      PCP went undiagnosed, partially due to the patient being unaware of his HIV
      positive status and partially because no organism could be found under the
      microscope.

PMID- 29066658
TI  - Successful maternal and perinatal outcomes in a term pregnancy with giant
      abdominopelvic leiomyomatosis.
AB  - A 30-year-old second gravida with history of laparoscopic myomectomy and one
      previous caesarean section was admitted at 31 weeks and 2 days period of
      gestation (POG) with a diagnosis of diffuse abdominopelvic leiomyomatosis and
      moderate anaemia. After correction of anaemia with intravenous iron and
      erythropoietin, laparotomy was performed at 37 weeks POG. A healthy female baby
      weighing 2.9 kg was delivered by classical caesarean section followed by
      hysterectomy in view of multiple fibroid uterus with uncontrolled bleeding.
      Debulking surgery was performed, and multiple large intraperitoneal leiomyomata
      with encasing blood vessels were removed. There was another 15*15 cm leiomyoma
      arising from the diaphragm which was excised. She received 4 units of packed red
      blood cells and fresh frozen plasma intraoperatively. The postoperative course
      was uneventful, both mother and baby were healthy and discharged 7 days after
      surgery.

PMID- 29066659
TI  - Sterile subdural empyema: an unusual presentation.

PMID- 29066660
TI  - Spontaneous right coronary artery dissection.

PMID- 29066661
TI  - Exercise-induced anaphylaxis in an elderly patient.
AB  - A 75-year-old Japanese woman presented with acute flushing pruritus and a feeling
      of diffuse warmth followed by collapse while dancing. After resting for 30 min
      and receiving a rapid infusion of 0.9% sodium chloride, her condition stabilised.
      She admitted that she had a similar experience 2 years earlier while dancing.
      Based on her history, her symptoms were attributed to exercise-induced
      anaphylaxis. None of the episodes was associated with any other suspicious
      cotriggers of anaphylaxis. She was successfully discharged from the clinic
      without any complications after receiving careful guidance on how to prevent this
      condition.

PMID- 29066662
TI  - Dysphagia management in bilateral frontal opercular syndrome (Foix-Chavany-Marie
      syndrome).
AB  - An 80-year-old woman was admitted to hospital with acute anarthria and severe
      dysphagia, characterised by loss of voluntary control of the muscles of facial
      expression, mastication, bolus manipulation (tongue) and pharyngeal constriction,
      with relative preservation of involuntary movements. Brain imaging revealed an
      acute infarct in the left frontal operculum and an area of gliosis consistent
      with an old infarct in the right frontal operculum. A clinical and radiological
      diagnosis of bilateral anterior frontal opercular syndrome (Foix-Chavany-Marie
      syndrome) was made.Deglutition consists of a voluntary oral stage and an
      involuntary pharyngeal and oesophageal phase. As involuntary movements were
      relatively preserved and no sensory loss was suspected, it was hypothesised that,
      once initiated or triggered, pharyngeal swallowing could be adequate. This was
      trialled at the bedside without adverse effects and subsequently videofluoroscopy
      demonstrated timely laryngeal elevation and closure, adequate opening of the
      upper oesophageal sphincter and smooth transit of the bolus from mouth to
      oesophagus. Oral intake was restored within days of admission and a percutaneous
      endoscopic gastrostomy was avoided. This is the first time to the authors'
      knowledge that this management approach has been described for this condition.

PMID- 29066663
TI  - Spontaneous painful subungual thumb haematoma.
AB  - We present the case of a 56-year-old man who presented to our accident and
      emergency department 15 years after a work-based injury to his left thumb.In
      January 2017, the patient was woken up acutely with excruciating pain in his left
      thumb with no preceding trauma. On clinical examination, only a subungual
      haematoma was noted. Radiographs of the effected thumb demonstrated a round,
      lytic lesion with an accompanying hairline fracture on the distal phalanx of the
      left thumb. The radiologist suggested a differential diagnosis of enchondroma
      should be considered.The patient was referred for a routine plastic surgery
      outpatient appointment. Curettage sampling of the lesion was performed and a
      cement filler was used to prevent further pathological fractures.The biopsy
      report stated that the sample contained normal bone tissue with no evidence of
      enchondroma or other malignancy and the patient was discharged without any
      further complications.

PMID- 29066664
TI  - Tramadol-induced hypoglycaemia.

PMID- 29066665
TI  - A proposal based on a review of reforms for improving medical education in India.

PMID- 29066666
TI  - Knowledge on infectious disease management among primary care physicians in
      Singapore and the effectiveness of an educational workshop intervention.

PMID- 29066668
TI  - Gibberellin Induces an Increase in Cytosolic Ca2+ via a DELLA-Independent
      Signaling Pathway.
AB  - DELLA proteins play a central role in gibberellin (GA) signaling. GA triggers
      DELLA degradation via the ubiquitin-proteasome pathway, thereby promoting plant
      growth. An increase in cytosolic Ca2+ ([Ca2+]cyt) was observed previously after
      several hours of GA application. Recent studies also suggest the existence of a
      DELLA-independent GA response. However, the effect of DELLA on the GA-induced
      increase in [Ca2+]cyt remains unknown. This study reexamined the effects of GAs
      on [Ca2+]cyt using the Ca2+ sensor protein aequorin in Arabidopsis (Arabidopsis
      thaliana). [Ca2+]cyt increased within a few minutes of GA treatment, even in
      transgenic plants expressing a mutated degradation-resistant version of REPRESSOR
      OF ga1-3 and in della pentuple mutant plants. In addition, it was also revealed
      that Ca2+ is not involved in DELLA degradation. These results suggest that the GA
      induced increase in [Ca2+]cyt occurs via a DELLA-independent pathway, providing
      important information on the GA signaling network.

PMID- 29066670
TI  - [Clinical Application of NGS-Based Clinical Sequencing].
AB  - Cancer Clinical Sequencing is a method for making the treatment decision for each
      cancer patient. Implication of the clinical sequencing is rapidly in progress in
      Japan. In general, the tumor FFPE samples obtained by biopsy or operatory
      resection are subjected to amplicon sequencing. The process was divided into pre
      analysis, analysis, and post-analysis processes. Quality assurance and control
      are necessary for all process. In addition, the expert members for clinical
      sequencing team is essential to make clinical sequencing reports based on the NGS
      analysis.

PMID- 29066667
TI  - Two SUMO Proteases SUMO PROTEASE RELATED TO FERTILITY1 and 2 Are Required for
      Fertility in Arabidopsis.
AB  - In plants, the posttranslational modification small ubiquitin-like modifier
      (SUMO) is involved in regulating several important developmental and cellular
      processes, including flowering time control and responses to biotic and abiotic
      stresses. Here, we report two proteases, SUMO PROTEASE RELATED TO FERTILITY1
      (SPF1) and SPF2, that regulate male and female gamete and embryo development and
      remove SUMO from proteins in vitro and in vivo. spf1 mutants exhibit abnormal
      floral structures and embryo development, while spf2 mutants exhibit largely a
      wild-type phenotype. However, spf1 spf2 double mutants exhibit severe
      abnormalities in microgametogenesis, megagametogenesis, and embryo development,
      suggesting that the two genes are functionally redundant. Mutation of SPF1 and
      SPF2 genes also results in misexpression of generative- and embryo-specific
      genes. In vitro, SPF1 and SPF2 process SUMO1 precursors into a mature form, and
      as expected in vivo, spf1 and spf2 mutants accumulate SUMO conjugates. Using a
      yeast two-hybrid screen, we identified EMBRYO SAC DEVELOPMENT ARREST9 (EDA9) as
      an SPF1-interacting protein. In vivo, we demonstrate that EDA9 is sumolyated and
      that, in spf1 mutants, EDA9-SUMO conjugates increase in abundance, demonstrating
      that EDA9 is a substrate of SPF1. Together, our results demonstrate that SPF1 and
      SPF2 are two SUMO proteases important for plant development in Arabidopsis
      (Arabidopsis thaliana).

PMID- 29066669
TI  - Arabidopsis beta-Amylase2 Is a K+-Requiring, Catalytic Tetramer with Sigmoidal
      Kinetics.
AB  - The Arabidopsis (Arabidopsis thaliana) genome contains nine beta-amylase (BAM)
      genes, some of which play important roles in starch hydrolysis. However, little
      is known about BAM2, a plastid-localized enzyme reported to have extremely low
      catalytic activity. Using conservation of intron positions, we determined that
      the nine Arabidopsis BAM genes fall into two distinct subfamilies. A similar
      pattern was found in each major lineage of land plants, suggesting that these
      subfamilies diverged prior to the origin of land plants. Moreover, phylogenetic
      analysis indicated that BAM2 is the ancestral member of one of these subfamilies.
      This finding, along with the conservation of amino acids in the active site of
      BAM2, suggested that it might be catalytically active. We then identified KCl as
      necessary for BAM2 activity. Unlike BAM1, BAM3, and BAM5, three Arabidopsis BAMs
      that all exhibited hyperbolic kinetics, BAM2 exhibited sigmoidal kinetics with a
      Hill coefficient of over 3. Using multi-angle light scattering, we determined
      that BAM2 was a tetramer, whereas BAM5 was a monomer. Conserved residues from a
      diverse set of BAM2 orthologs were mapped onto a homology model of the protein,
      revealing a large, conserved surface away from the active site that we
      hypothesize is a secondary carbohydrate-binding site. Introduction of bulky
      methionine for glycine at two points on this surface reduced catalytic activity
      significantly without disrupting the tetrameric structure. Expression analysis
      indicated that BAM2 is more closely coexpressed with other starch degradation
      enzymes than any other BAM, suggesting that BAM2 may play an important role in
      starch degradation in plants.

PMID- 29066671
TI  - [Landscape of Lung Cancer with Oligometastasis].
AB  - Lung cancer with a few to several metastases is so-called oligometastatic
      disease. Patient with recurrence only to limited site is also known as oligo
      recurrence, and may be included as oligometastatic disease. From biological
      aspect, any existence of metastases is a sign of systemic disease. Due to the
      reports of long survival with only local treatment and without systemic disease
      in oligometastatic lung cancer, word of oligometastasis is used with fascinating
      expectation of cure to advanced lung cancer. Most of the previous reports are
      retrospective and no comprehensive data exists for selecting patient for local
      treatment to oligometastasis. Recent positive result of randomize phase II study
      is followed up with phase III study. Progress in treatment of advanced non-small
      cell lung cancer with targeted therapy to oncogenic-driver(EGFR, ALK, ROS1 and
      others) and immune-checkpoint inhibitor(PD-1 pathway inhibitors)makes it
      difficult to define the appropriate indication of local treatment to
      oligometastatic lung cancer.

PMID- 29066672
TI  - [Treatment Strategy for Liver Metastasis of Colorectal Cancer - Including
      Treatment for Oligometastasis].
AB  - The mainstay of treatment for metastatic colorectal cancer is surgery. Therefore,
      colorectal cancer metastasis is distinctive, compared to other cancer types in
      which chemotherapy is the main treatment. Initially, Japan experienced medical
      druglag compared with western countries. However, the use of oxaliplatin for
      unresectable recurrent metastatic colorectal cancer became available in Japan, as
      well as in western countries, in 2005. We have since shifted chemotherapeutic
      regimens from monotherapy to combination therapy with molecular targeted agents.
      The combination therapy has rapidly become a standard therapy for unresectable
      metastatic colorectal cancer, and prognosis has dramatically increased for
      patients with this condition. Herein, we describe the treatment of liver
      metastasis of colorectal cancer, and surgery and adjuvant or neoadjuvant therapy
      options for resectable cancer. Furthermore, we focus on conversion therapy for
      unresectable cancer.

PMID- 29066673
TI  - [Treatments for Pancreatic Cancer with Oligometastasis].
AB  - Pancreatic cancer, adenocarcinoma, generally rapidly progresses, and if a
      metastatic lesion is detected, chemotherapy is applied even in solitary
      metastasis. However, surgical resection for solitary metastasis have been
      reported to achieve long survival in some pancreatic cancer patients. In a
      prospective study of surgery for hepatic and lymph node oligometastasis of
      pancreatic cancer, long survival of 5 years or more was reported around 10%.
      Furthermore, longer survival and fewer rerecurrence were achieved with surgery in
      lung metastasis than in liver metastasis and loco-regional recurrence. Although
      there has been no establishment of concept or no consensus of treatment strategy
      for oligometastasis in pancreatic cancer, some patients with pancreatic cancer
      have long disease-free survival by surgery for oligometastasis. A population of
      pancreatic cancer patients who have benefits of surgery for oligometastasis
      should be identified, and it is necessary to establish treatments for
      oligometastasis as standard treatments in pancreatic cancer.

PMID- 29066674
TI  - [Treatment Strategy in Patients with Oligometastatic Breast Cancer].
AB  - Oligometastases means the state which the anatomy and physiology may limit or
      concentrate metastases to a single or a limited number of organs. In patients
      with oligometastatic breast cancer their prognosis may be good, although the
      impact of local therapy has not been evaluated prospectively. The development of
      minimally invasive surgical techniques and highly conformal ablative radiotherapy
      allow for safe and effective ablation of metastatic lesions in most locations. A
      biopsy(preferably providing histology)of a metastatic lesion has been recommended
      to confirm diagnosis particularly when metastasis is diagnosed for the first
      time. Biology markers(especially HER2 and hormone receptor)should be reassessed
      because it may differ from the primary tumor. Although some retrospective studies
      have suggested that achieving a sustained complete remission seems to be
      associated with a longer survival, the true impact of these local-regional
      therapies on long-term outcome remains unknown, and if possible, randomized
      trials are needed.

PMID- 29066675
TI  - [Liver, Pancreas, Biliary Tract New Therapeutic Strategies for Advanced
      Pancreatic Cancer].

PMID- 29066676
TI  - [I. The Efficacy of Preoperative Adjuvant Treatment for Pancreatic Ductal
      Adenocarcinoma Based on the Resectability Criteria according to JPS 7th].

PMID- 29066677
TI  - [II.Portal Vein Resection during Pancreaticoduodenectomy].

PMID- 29066678
TI  - [III. Pancreaticoduodenectomy with Arterial Resection and Reconstruction].

PMID- 29066679
TI  - [IV. Distal Pancreatectomy with Celiac Axis Resection(DP-CAR)for Locally Advanced
      Pancreatic Cancer with Celiac Artery Invasion].

PMID- 29066680
TI  - [Fresh Frozen Plasma Provides Endothelial Protection When Administered Early
      after Stem Cell Transplantation].
AB  - BACKGROUND: Veno-occlusive disease(VOD)is a fatal coagulopathy, which is caused
      by an endothelial disorder among patients who undergo hematopoietic stem cell
      transplantation(SCT). Some protective agents, such as administration of fresh
      frozen plasma(FFP), have been evaluated for both prophylactic and targeted
      therapy. PURPOSE: We evaluated the prophylactic efficacy of FFP for VOD in a
      retrospective study. METHODS: We surveyed patients who received SCT in our
      hospital between January 2011 and December 2011. We reviewed their data and
      compared those who were administered prophylactic FFP in the early
      transplantation period(up to day 60)with those who did not receive prophylactic
      FFP. RESULTS: A total of 14 cases were evaluated: 7 female and 7 male, with a
      median age of 50 years(range of 24 to 63 years). Fibrinogen significantly
      increased in the FFP group compared with the non-FFP group(p=0.0125). Although
      the hemostasis parameters of prothrombin time, activated partial thromboplastin
      time, and D-dimer were all comparable between the 2 groups, the level of
      fibrinogen degradation products(FDP)was significantly attenuated in the FFP group
      compared with the non-FFP group(p= 0.0140). Of note, we observed 2 peaks in the D
      dimer/FDP ratio in the engraftment period(around day 18)and postengraftment(
      around day 35)compared with the non-FFP group. Overall survival did not
      significantly differ between the 2 groups(502 days for FFP, and 586 days for non
      FFP, p=0.777). DISCUSSION: Prophylactic administration of FFP improved
      hypofibrinogenemia and FDP accumulation in this retrospective analysis of
      patients who received SCT. We speculate that prophylactic FFP treatment for
      dyscoagulopathy is effective due to supplementation of coagulation factors.
      Further study, including randomized trials, is warranted in order to confirm this
      hypothesis.

PMID- 29066681
TI  - Successful Treatment with 5-fluorouracil and Levofolinate Calcium in Advanced
      Gastric Cancer Patient with Disseminated Intravascular Coagulation.
AB  - A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone
      metastases. Chemotherapy in the first, second and third-line was not effective.
      Blood examinations showed disseminated intravascular coagulation(DIC)at the end
      of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5
      fluorouracil and levofolinate calcium was performed. This resulted in a good
      response for DIC. This palliative therapy was effective and safety.

PMID- 29066682
TI  - [A Case of Bilateral Lymph Node Metastases of Rectal Cancer Treated with
      Chemotherapy and Surgery].
AB  - We present a case of bilateral lymph node metastases of rectal cancer treated
      with chemotherapy and surgery. The patient was a 65-year-old man with upper
      rectal cancer. Laparoscopic low anterior resection(LAR)was performed.
      Pathological findings were tub2>por>muc, pT3, ly2, v3, pN2, pM0. Six months after
      surgery, the CEA level was elevated. CT and PET-CT confirmed bilateral metastasis
      to the lymph nodes. Five courses of FOLFOX4 plus bevacizumab were administered,
      and then, we performed laparoscopic bilateral lymph node dissection. Pathological
      assessments confirmed scarring and fibrosis, that is, a pathological complete
      response(pCR)was achieved. Two years and 6 months after surgery, no recurrence
      was detected. After chemotherapy or chemoradiotherapy, we should perform surgery
      to prevent local recurrence, especially to the lateral lymph nodes.

PMID- 29066683
TI  - [Cardiac Diffuse Large B-Cell Lymphoma Presenting with Acute Heart Failure Due to
      Cardiac Tamponade].
AB  - A 75-year-old man was admitted to our hospital in May 2016 with progressive
      shortness of breath. We considered him to be experiencing acute heart failure
      caused by atrial fibrillation. Contrast-enhanced computed tomography showed a
      hypodense mass involving the right atrium and left ventricle, pericardial
      effusion, and lymphadenopathy of the groin. Histological finding from the groin
      and pericardial effusion analysis showed diffuse large B-cell lymphoma(DLBCL). We
      thus diagnosed this patient with cardiac tamponade owing to the involvement of
      the heart by DLBCL. Treatment was initiated with tetrahy-
      dropyranyldoxorubicin/cyclophosphamide/vincristine/prednisolone(THP
      COP)therapy(50% dose)and continuous pericardial drainage. We carefully added
      rituximab 4 days after monitoring his symptoms and vital signs. There were a few
      adverse effects, and after treatment, the mass and pericardial effusion
      disappeared. Subsequently, 8 courses of THP-COP therapy accompanied by
      rituximab(R-THP-COP)(full dose)were administered, resulting in a complete
      response.

PMID- 29066684
TI  - [Novel Therapeutic Strategy for Human Epidermal Growth Factor Receptor 2-Positive
      Gastric Cancer].
AB  - Trastuzumab(Tmab), a humanized monoclonal antibody that selectively targets human
      epidermal growth factor receptor 2(HER2), is currently used in the clinical
      setting for the treatment of both breast and gastric cancer. While Tmab has shown
      improvements in patient prognoses, acquired resistance to this agent remains an
      issue. While some novel HER2-targeted agents have been approved for clinical use
      in breast cancer, no such agent has shown treatment efficacy for gastric
      malignancies with Tmab-resistance. Nanotechnology, which has progressed rapidly,
      has been applied to medical fields in recent years. Gold nanoparticles, which are
      characterized by their in vivo stability and ease of surface modification, have
      been reported to show efficacy as the carriers of therapeutic agents, such as
      drugs, antibodies, peptides, and nucleic acids. In this work, we developed Tmab
      conjugated gold nanoparticles and demonstrate their efficacy for the treatment of
      HER2-positive, Tmabresistant gastric cancer cell lines. Our findings demonstrate
      that Tmab-conjugated gold nanoparticles have the potential to be a novelHER2 
      targeted therapeutic agent.

PMID- 29066685
TI  - [Indoleamine 2,3-Dioxygenase Activity during Fulvestrant Therapy for Aromatase
      Inhibitor Resistant Metastatic Breast Cancer].
AB  - We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)for
      breast cancer patients between different clinical stages and patient ages. IDO
      activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn
      levels were measured using high performance liquid chromatography(HPLC). Serum
      Trp/Kyn levels in Stage IV breast cancer patients were lower than in patients at
      other stages. Serum Trp/Kyn levels of breast cancer patients over the age of 70
      years were lower than in patients under the age of 69 years. Within the same
      clinical stage, serum Trp/Kyn levels of breast cancer patients over the age of 70
      years were lower than in patients under the age of 69 years. These results
      suggest that the immunological profile of breast cancer patients over the age of
      70 years may be immunosuppressive compared to breast cancer patients under the
      age of 69 years.

PMID- 29066686
TI  - [Regulation of PD-L1 by MicroRNA in Mismatch Repair Deficient-Colorectal Cancer].
AB  - Programmed cell death 1(PD-1)/PD-ligand 1(PD-L1)immune checkpoint blockade has
      emerged as a promising therapeutic strategy in various types of cancer. In a
      recent phase II clinical trial, treatment with the anti-PD-1 agent,
      pembrolizumab, resulted in considerable clinical benefit in patients with
      mismatch repair(MMR)-deficient colorectal cancer(CRC). Upregulation of PD-1on T
      cells and PD-L1 on tumor cells induces inhibitory signals to suppress T-cell
      activation, leading to an immune-suppressive microenvironment particularly in MMR
      deficient tumors. However, the regulation of PD-L1 expression on CRC cells is
      poorly understood. We hypothesized that certain microRNAs(miRNAs)are involved in
      the immunosuppressive microenvironment by directly targeting PD-L1. We identified
      candidate miRNAs by RNA-sequence analyses for mRNA and miRNA expression obtained
      from the TCGA colon adenocarcinoma database combined with miRNA target prediction
      programs. We found that forced miRNA expression could decrease PD-L1 expression
      on cancer cell lines. Our findings may facilitate an understanding of the role of
      miRNAs in PD-L1 regulation and also suggest potential miRNAs to serve as
      biomarkers and therapeutic targets for cancer immunotherapy.

PMID- 29066687
TI  - [Indoleamine 2,3-Dioxygenase Activity during Letrozol Therapy for an Elderly
      Breast Cancer Patient].
AB  - We evaluated the clinical significance of indoleamine 2,3-dioxygenase(IDO)during
      letrozol therapy for an elderly patient with locally advanced breast cancer. IDO
      activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn
      levels were measured using high performance liquid chromatography(HPLC). Serum
      Trp/Kyn levels of the patient before endocrine therapy were lower than those
      after endocrine therapy. IDO activity decreased after endocrine therapy and
      correlat- ed with the number of metastatic lymph node lesions during letrozol
      therapy. These results suggest that measuring the Trp/ Kyn ratio may be useful
      for evaluating immunological metastatic status during endocrine therapy in
      elderly patients with locally advanced breast cancer.

PMID- 29066688
TI  - [Survival Benefit by Combined Administration of Cyclophosphamide, Lentinula
      edodes Mycelia Extract(LEM), and Ganoderma lucidum Mycelia Extract(MAK)in
      S1018B10 Tumor-Bearing Mice].
AB  - Cyclophosphamide(CY)was intraperitoneally administered once a week to
      C57BL/10mice that had received Rous sarcoma virus(RSV)-induced S1018B10 syngeneic
      tumor transplantation and in whom tumor diameter exceeded 4.5 mm. Survival was
      prolonged in a group of mice that also received a mixture of LEM and MAK orally.
      When splenic cells were cultured under mitomycin C-treated S1018B10 stimulation
      and the S1018B10-directed cell killing ability was examined, the effector cells
      were found to be F4/80 - DC/Mf cells. Flow cytometric analysis showed that the
      proportion of F4/80- DC/Mf cells in the splenic cell culture of the CY+LEM+MAK
      treatment group was higher than that in the untreated group. The ratio of F4/80+
      CD8a+ cells in the CY+LEM+MAK treatment group was lower than that in the
      untreated group.

PMID- 29066689
TI  - [Analysis of Patients Who Received Enteral Nutrition in the Course of
      Chemotherapy].
AB  - BACKGROUND: Chemotherapy-related adverse events can deteriorate the quality of
      life, as well as chemotherapy tolerance, for patients with gastric cancer.
      Nutritional support may prevent chemotherapy-related adverse events. METHODS:
      Five patients who received chemotherapy for advanced gastric cancer were
      prescribed enteral nutrition(Elental(r)or ENEVO(r)). We retrospectively evaluated
      the efficacy and safety of chemotherapy while receiving enteral nutrition.
      RESULTS: All patients consumed more than one bottle of enteral nutrition during
      chemotherapy. Median progression-free survival(PFS)and overall survival(OS)were
      166 days(100-349)and 328 days(115-431), respectively. Major Grade 3 or 4 adverse
      events included neutropenia(0%), anemia(40%), and diarrhea(20%). The prognostic
      nutritional index(PNI)was higher than 40, and the neutrophil lymphocyte
      ratio(NLR)was lower than 3 over the course of chemotherapy. CONCLUSIONS:
      Nutritional support for gastric cancer patients receiving chemotherapy is
      feasible. There was a low incidence of chemotherapy-related hematological
      toxicity, with a relatively longer PFS in patients receiving enteral nutrition.

PMID- 29066690
TI  - [Preoperative Prognostic Nutrition Index Is a Predictive Factor of Complications
      in Laparoscopic Colorectal Surgery].
AB  - : Paitients and methods: We retrospectively reviewed a database of 188 patients
      who underwent resection for colorectal cancer with laparoscopic surgery between
      July 2007 and March 2015. The prognostic nutrition index(PNI), modified Glas- gow
      prognostic score(mGPS), controlling nutritional status(CONUT), and
      neutrophil/lymphocyte ratio(N/L)were measured in these patients. We examined the
      association between postoperative complications and clinicopathological factors.
      RESULTS: The study included 110 men and 78 women. Median age was 68 years. The
      site of the primary lesion was colon in 118 and rectum in 70 patients.
      Postoperative complications higher than Grade II(Clavien-Dindo
      classification)were reported in 24(12.8%)patients: Surgical site infection(SSI)in
      12, remote infection in 7, ileus in 5, and others in 2 patients.
      Clinicopathological factors related to complications were rectal surgery, large
      amount of intraoperative bleeding, and long operative time. The related
      immunologic and nutritional factors were mGPS 2, PNI below 40, and N/L above 3.
      CONUT was not associated with complications in ourcases. CONCLUSIONS: mGPS, PNI,
      and N/L are predictive factors for complications in laparoscopic colorectal
      surgery.

PMID- 29066691
TI  - [A Prognostic Factor Based on Inflammation, Nutrition, and Immune Status for
      fStage II/III Colorectal Cancer].
AB  - INTRODUCTION: We investigated whether the prognostic nutritional index(PNI),
      controlling nutritional status(CONUT), modified Glasgow prognostic score(mGPS),
      and the neutrophil count/lymphocyte number ratio(NLR)could be prognostic factors
      for fStage II/III colorectal cancer. SUBJECTS AND METHODS: The subjects were 115
      patients with fStage II/III colorectal cancer who underwent curative resection.
      We studied the relationship with 3-year disease-free survival(DFS)and 5-year
      survival rate(OS). RESULTS: DFS and OS were 75.6% and 84.4%, respectively, and
      81.3% and 69.6% for DFS and 82.4% and 84.4% for OS were in fStage II and III,
      respectively. Univariate analysis of DFS showed significant differences for sex,
      age, PNI, and NLR, but there was no difference in PS, location, adjuvant
      chemotherapy, CONUT, or mGPS. In multivariate analysis, sex(male)and NLR(>2)were
      independent prognostic factors(p=0.006 and p=0.01, respectively). As for OS,
      although significant differences were recognized for sex, age, PS, PNI, NLR, and
      CONUT, there was no difference in location, adjuvant chemotherapy, or mGPS. In
      multivariate analysis, PS(>=1)and NLR(>2)were independent prognostic
      factors(p=0.009 and p=0.006, respectively). CONCLUSIONS: NLR(>2)was an
      independent prognostic factor for DFS and OS among prognos- tic factors based on
      inflammation, nutrition, and immunity in fStage II/III colorectal cancer
      patients.

PMID- 29066692
TI  - [Clinical Evaluation of Immunosuppressive Acidic Protein in the Serum of Patients
      with Inflammatory Breast Recurrence].
AB  - Inflammatory breast recurrence after breast conserving surgery often compromises
      patient quality of life(QOL)and is associated with a poor prognosis. For this
      type of recurrence, the immunological situation of the patient is uncertain. We
      evaluated the clinical significance of immunosuppressive acidic protein(IAP)in
      the serum of patients with inflammatory breast recurrence during treatment. We
      collected serum from 3 patients at three different time points: the pre-treatment
      phase, recurrence phase, and the post-treatment phase. IAP was then measured from
      these multiple serum samples. There was a significant difference between serum
      IAP values in the pre-treatment and recurrence phases. The recurrence phase had a
      mean IAP value that was higher than the pre-treatment phase. The IAP values were
      indicative of the disease condition. These results suggest that serum IAP is a
      useful quantification of the immunological condition of patients with
      inflammatory breast recurrence.

PMID- 29066693
TI  - [The Impact of Neutrophil-Lymphocyte Ratio on the Prognosis in Patients Who
      Underwent Esophagectomy for Esophageal Cancer].
AB  - BACKGROUND: Thene utrophil-lymphocyteratio (NLR)reflects a patient's systemic
      inflammatory response. Several studies have revealed that the NLR is associated
      with a poor prognosis in several types of malignant tumors such as colorectal and
      lung cancer. The aim of this study was to evaluate the impact of preoperative NLR
      on the prognosis of patients with esophageal cancer. METHODS: The NLR was
      calculated for 93 consecutive patients with clinical Stage II or III esophageal
      cancer, who underwent curative esophagectomy following neoadjuvant chemotherapy
      between 2011 and 2013. The impact of preoperativeNLR on overall survival(OS)after
      esophagectomy was evaluated. The NLR cut off value was set to 2. RESULTS: The 3
      year OS of patients with NLR>=2 was significantly shorter than patients with
      NLR<2(40.5% vs 67.9%, p=0.005). In a multivariateCox model, NLR>=2(HR: 2.342,
      95%CI: 1.095-5.007, p=0.028), pathological depth of tumor(HR: 3.207, 95%CI: 1.114
      9.233, p=0.031), and an ageove r 60(HR: 2.342, 95%CI: 1.117-6.501, p=0.027)were
      identified as independent prognostic factors for OS after esophagectomy.
      CONCLUSIONS: The preoperative NLR was significantly associated with a poor
      prognosis in esophageal cancer patients who underwent curative esophagectomy
      following neoadjuvant chemotherapy.

PMID- 29066695
TI  - [Standard Chemotherapy with Bevacizumab as First-Line Therapy for Metastatic
      Colorectal Cancer with RAS Mutation].
AB  - AIM: We examined the outcome of treatment with first-line chemotherapy with
      bevacizumab(Bmab)formetastatic colorectal cancer in our hospital to clarify the
      outcome for RAS mutant patients. SUBJECTS AND METHODS: From January 2013 to April
      2016, 28 patients who initiated standard chemotherapy(2 chemotherapeutic
      agents)with Bmab as the first-line regimen for metastatic colorectal cancer were
      enrolled in this retrospective study. Time to treatment failure(TTF)and overall
      survival(OS)were analyzed. RESULTS: The median age was 66.5(46-81)years old,
      including 16 men and 12 women, 11 cases with RAS wild type, and 17 cases with
      mutant type. The response rate was 30.8% in 2 cases of CR, 6 cases of PR, 14
      cases of SD, 4 cases of PD, and 4 cases with conversion surgery after
      chemotherapy. TTF was 6.5 months and OS was 32.1 months. Among those with RAS
      mutations, 3 cases received conversion surgery. TTF of the mutant and wild type
      were 6.3 and 5.6 months, respectively, and OS was 35.8 and 32.1 months,
      respectively, without any significant difference. In addition, excluding
      conversion cases, the OS of mutant and wild type patients was 22.7 and 29.5
      months, respectively. CONCLUSION: The outcome of treatment using first-line
      chemotherapy with Bmab for metastatic colorectal cancer with RAS mutations was
      retrospectively analyzed. There was no difference in therapeutic effect between
      RAS mutated and not, and it seems that an OS of more than 20 months can be
      expected for those with RAS mutations with this choice of treatment.

PMID- 29066694
TI  - [Clinical Evaluation of Indoleamine 2, 3-Dioxygenase in the Serum of Patients
      with Locally Advanced Breast Cancer during Mohs Paste Treatment].
AB  - Locally advanced breast cancer lesions often compromise patients' quality of
      life(QOL). Mohs paste is a histopathological fixative with zinc chloride as the
      main ingredient. It is applied when performing chemosurgery for skin tumors. In
      recent years, this paste has reportedly been very effective for the control of
      various symptoms of skin metastases in inoperable advanced cancers, such as
      pungent odor and hemorrhage, in the field of palliative care. We evaluated the
      clinical significance of indoleamine 2, 3-dioxygenase(IDO)in the serum of
      patients with locally advanced breast cancer during Mohs paste treatment. IDO
      activity was measured by the tryptophan(Trp)/kynurenine(Kyn)ratio. Trp and Kyn
      levels were measured using high performance liquid chromatography(HPLC). We
      collected serum samples from 3 locally advanced breast cancer cases: once in the
      pre-treatment phase, 2 times in the post-treatment phase, and 5 times in the post
      treatment phase. Then, we measured the Trp/Kyn ratio and CRP in these samples
      during Mohs paste treatment. There were no significant differences in serum Trp/
      Kyn ratios between the phases, but serum CRP values decreased after Mohs paste
      treatment. These results suggest that Mohs paste treatment for locally advanced
      breast cancer lesions may be useful in enhancing patients' QOL without
      immunosuppression.

PMID- 29066696
TI  - [Relationship between Surgical Site Infection(SSI)Incidence and Prognosis in
      Colorectal Cancer Surgery].
AB  - We examined the relationship between risk factors for surgical site
      infections(SSIs)and prognosis in 440 patients who underwent colon cancer surgery.
      We evaluated factors related to SSIs(GradeB II)and compared survival rates by
      stage. SSIs were observed in 36 patients. An increased SSI incidence was
      associated with pulmonary dysfunction, mGPS=2, CONUT>=2, PNI<=40, NLR>4.3,
      location(rectum), depth of tumor invasion(Bsubserosa, SS), lymph node metastasis,
      laparotomy, resection of other organs, colostomy, blood loss(large), and
      operative time(long). Survival rates were lower in Stage II/III patients with
      SSIs. Preoperative risk judgment is important in colorectal cancer surgery.

PMID- 29066697
TI  - [A Case of Surgical Resection of Hepatic Leiomyosarcoma].
AB  - A 72-year-old woman was referred to our hospital due to an abdominal mass.
      Ultrasound sonography and computed tomography revealed liver tumors in liver
      segments 2 and 3. The preoperative diagnosis was hepatocellular carcinoma. The
      patient underwent an extended left lobectomy. Histological examination of
      resected specimens revealed that the tumors were hepatic leiomyosarcoma. We
      report our experience of this hepatic leiomyosarcoma, along with the literature
      on this tumor type.

PMID- 29066698
TI  - [A Case of Pancreatic Neuroendocrine Tumor with Necrolytic Migratory Erythema].
AB  - A 45-year-old man was admitted because of necrolytic migratory erythema. A
      computed tomographic scan of the abdomen revealed a 4.5cm mass in the tail of the
      pancreas. We performed distal pancreatectomy and splenectomy, and a definitive
      diagnosis of pancreatic neuroendocrine tumor(WHO class grade 2)was made
      histopathologically.

PMID- 29066699
TI  - [A Case of Roux-en-Y Loop Reconstruction Using a Modified Aboral Pouch Technique
      for Y-Limb Obstruction Following Distal Gastrectomy].
AB  - A 53-year-old man underwentdistal gastrectomy with Roux-en-Y(R-Y)reconstruction
      for gastric cancer. An R-Y anastomosis was performed usinga 21mm circular
      stapler. Five years postoperatively, he visited our hospital with anorexia. An
      abdominal computed tomography scan showed dilatation of the afferent loop. He was
      diagnosed with afferent loop syndrome due to R-Y anastomotic stenosis that
      resulted in poor oral intake and malnutrition. A U-shaped bend created by an
      adhesion caused a bowel obstruction of the Y-anastomotic site for which the
      patient underwent R-Y loop reconstruction with an aboral pouch usinga 60mm linear
      stapler. He has been well without postoperative complaints. Here, we report a
      case of R-Y loop reconstruction with an aboral pouch for afferent loop
      obstruction complicated by stenosis of the Y-anastomotic site after distal
      gastrectomy.

PMID- 29066700
TI  - [A Case of Laparoscopic Repair of Internal Hernia after Laparoscope-Assisted
      Distal Gastrectomy with Antecolic Roux-en-Y Reconstruction].
AB  - A 72-year-old woman had undergone laparoscope-assisted distal gastrectomy with D1
      plus lymph node dissection and antecolic Roux-en-Y reconstruction for early
      gastric cancer. She visited our department outpatient clinic with left upper
      abdominal pain 1 year and 9 months after the surgery. CT revealed a spiral sign
      of the superior mesenteric arteriovenous branch. An internal hernia was suspected
      on hospitalization. Although abdominal symptoms were relieved by conservative
      treatment, the hernia persisted. Laparoscopic surgery was performed and revealed
      that almost entire small intestine had been affected due to Petersen's defect.
      Since no ischemic changes were observed, the defect was repaired laparoscopically
      with suture closure. There has been no recurrence of internal hernia after the
      laparoscopic surgery. Internal hernia after distal gastrectomy is relatively
      rare. However, the risk of internal hernia is high due to the gap between the
      elevated jejunum and transverse colon mesentery in Roux-en-Y reconstruction and
      can lead to intestinal necrosis. Since an internal hernia can occur in patients
      who have undergone gastric resection with Roux-en-Y reconstruction, suture
      closure of Petersen's defect should be performed to prevent this occurrence.

PMID- 29066701
TI  - [A Case of Fournier's Gangrene Due to Perforation of Lower Rectal Cancer during
      Chemotherapy].
AB  - Fournier's gangrene is a rapidly progressing bacterial infection, involving the
      subcutaneous and deep fascia. Although intestinal perforation after treatment
      with bevacizumab is well known, Fournier's gangrene rarely occurs during
      chemotherapy. A 73-year-old man with unresectable rectal cancer during
      chemotherapy involving the mFOLFOX6 plus bevacizumab regimen had a consciousness
      disorder and was admitted to our hospital on emergency. Computed tomography scans
      indicated a necrotizing soft tissue infection with large amounts of pneumoderma
      throughout the perineum. He was diagnosed as having Fournier's gangrene via
      perforation of rectal cancer, and urgent operation was performed. After
      debridement of the skin and soft tissue around the perineum, loop sigmoidostomy
      was performed. A nice granulated tissue bed over the perineum was formed via
      daily lavage with sarin. Although the patient was taken back to the operation
      theater for ileostomy, he could resume chemotherapy involving mFOLFOX6 without
      bevacizumab 50 days after the initial operation. It is necessary to pay attention
      to Fournier's gangrene via perforation during chemotherapy with bevacizumab in
      patients with lower rectal cancer.

PMID- 29066702
TI  - [Two Cases in Which Eribulin Mesylate Was Effective for Taxane-Resistant Advanced
      Breast Cancer].
AB  - We experienced 2 cases in which eribulin mesylate was effective for taxane
      resistant advanced breast cancer. Case 1: A 65- year-old woman was diagnosed with
      advanced breast cancer(T4cN2aM0, stage III B)and treated with
      chemotherapy(nabpaclitaxel). Bone metastasis was observed; then, she sequentially
      received epirubicin and cyclophosphamide, nab-paclitaxel, and bevacizumab and
      paclitaxel. However, lung metastases appeared, and we changed the regimen to
      eribulin mesylate. We administered 11 courses of eribulin mesylate before bone
      marrow metastasis appeared. Eribulin mesylate was effective for more than 1 year.
      Case 2: A 77-year-old woman was diagnosed with advanced breast cancer(T4bN3cM1,
      stage IV), and liver and pleural metastasis were observed during an examination
      at the first visit. Four courses of nab-paclitaxel were administered, but because
      of the increase in pleural effusion, we changed the regimen to eribulin mesylate.
      Thirteen courses of eribulin mesylate were administered before the disease
      progressed. The progression-free survival was 9.53 months. Through the 2 cases in
      which eribulin mesylate was effective for taxane-resistant advanced breast
      cancer, the effect of eribulin mesylate compared to taxane was clinically
      inferred.

PMID- 29066703
TI  - [A Case Report of Long-Term Survival after SOX Chemotherapy for Metastatic
      Ovarian Tumor of Gastric Cancer].
AB  - A 55-year-woman presented with abdominal fullness. An abdominal MRI disclosed
      ovarian and uterine tumors. Under the pathological diagnosis of Kruckenberg
      tumor, total hysterectomy and bilateral adenexectomy were performed.
      Gastrointestinal endoscopy disclosed type 3 on the greater curvature and anterior
      wall of the middle gastric body. The gastric cancer had a similar histology,
      which suggested the tumor origin and led to the diagnosis of c-stage IV. She
      received 6 courses of SOX chemotherapy. Staging laparoscopy revealed no
      peritoneal metastasis and negative cytodiagnosis of ascites. She underwent total
      gastrectomy with D2 lymphadenectomy. In May 2017, after S-1 chemotherapy, no
      metastasis to other organs was observed.

PMID- 29066704
TI  - [Two Cases of Unresectable Advanced Rectal Cancer with a Long-Term Survival for
      Which Pathological Complete Response Was Achieved through Neoadjuvant Effective
      Chemotherapy].
AB  - We report 2 unusual cases of Stage IV rectal cancer for which pathological
      complete response was achieved with neoadjuvant chemotherapy(NAC)consisting of a
      combination of 5-fluorouracil(5-FU), oxaliplatin, Leucovorin(mFOLFOX6)or
      irinotecan(FOLFIRI), and bevacizumab, without radiotherapy. Case 1: A 65-year-old
      man was diagnosed as having rectal cancer with an invasive carcinoma of the
      prostate and lymph node metastasis. He refused to undergo surgery and received
      NAC instead. After NAC with mFOLFOX6 and FOLFIRI was performed, CT scan and
      colonoscopy revealed no evidence of disease. The subsequent result was compatible
      with a complete pathological response. The patient is currently alive 4 years
      after the first chemotherapy, without evidence of recurrence and adjuvant
      chemotherapy. Case 2: A 75-year-old man was diagnosed as having rectal cancer
      with an invasive carcinoma of the bladder and lymph node metastasis. After
      providing neoadjuvant bevacizumab-containing chemotherapy, low anterior resection
      of the rectum was performed. Operative findings showed that the tumor was only
      ulcer and the lymph nodes were not enlarged. The subsequent results indicated
      that pathological findings revealed no cancer and a complete pathological
      response. In conclusion, the survival benefits from NAC are still unclear for
      patients with an initially unresectable rectal cancer. We report 2 rare cases of
      rectal cancer with long survival and a complete pathological response after
      neoadjuvant chemotherapy.

PMID- 29066705
TI  - [Anti-EGFR Antibody Combination Chemotherapy Was Effective against Locally
      Advanced Ascending Colon Cancer as Well as a Recurrent Lesion - A Case Report].
AB  - Here we report a case in which a locally advanced ascending colon cancer was
      successfully treated with anti-EGFR immunotherapy combined with chemotherapy and
      curative resection, and recurrent cancer was treated with the same chemotherapy.
      A 71-year-old man was diagnosed with ascending colon cancer in our department. No
      distant metastasis was observed, but curative resection was considered impossible
      because of extensive local cancer invasion. Because a genetic analysis revealed
      the presence of the wild-type KRAS gene, 6 courses of mFOLFOX6 plus cetuximab
      were administered. A cPR was obtained and curative resection was performed. The
      final diagnosis was ypT3N1M0, ypStage III a colon cancer, and chemotherapy
      improved the cancer stage to Grade 1b. Six courses of FOLFOX6 were then
      administered, followed by observation. After 2 years 6 months, a tumor of
      approximately 5 cm in size was noted in the right buttock using surveillance CT
      and was diagnosed as recurrent colon cancer. We considered further curative
      resection difficult and therefore 6 courses of mFOLFOX6 plus panitumumab were
      administered, a cPR was obtained, and right hip tumor extirpation surgery was
      performed. These results suggest that chemotherapy combined with anti-EGFR
      antibody immunotherapy is effective in treating recurrent colon cancer.

PMID- 29066706
TI  - [Three Cases of High-Grade Malignant Cancer of Unknown Primary with a Long-Term
      Survival].
AB  - We report 3unusual cases of cancer of unknown primary(CUP)with a long-term
      survival after chemotherapy. A 56-yearold man was diagnosed as having CUP with
      invasion of an enlarged carcinoma 20 cm in size to the pancreas and peritoneal
      dissemination. He received chemotherapy with paclitaxel, carboplatin, and
      gemcitabine. After the chemotherapy, CT scan and PET-CT revealed no evidence of
      disease, so tumor resection was performed. The subsequent pathological findings
      revealed no cancer and a complete pathological response. The patient is currently
      alive 4 years after the first surgery, without evidence of recurrence and
      adjuvant chemotherapy. A 60-year-old man was diagnosed as having CUP with an
      undifferentiated carcinoma and lymph node metastasis. He received chemotherapy
      with paclitaxel, carboplatin, and gemcitabine. However, unanticipated adverse
      events(finger ulcer)occurred. Thus, the chemotherapy was changed to paclitaxel,
      carboplatin, and etoposide. The patient is currently alive 4.2 years after the
      first chemotherapy, without evidence of recurrence. A 59-year-old man was
      diagnosed as having CUP with neuroendocrine carcinoma(NEC)and lymph node
      metastasis. He received chemotherapy with irinotecan and cisplatin. The lymph
      node metastases disappeared, but bone metastasis was found. The chemotherapy was
      changed to paclitaxel, carboplatin, and etoposide. The patient is currently alive
      3.5 years after the first chemotherapy, without evidence of recurrence. We report
      3rare cases of high-grade malignant CUP with complete pathological response,
      partial response, stable disease, and long-term survival after chemotherapy.

PMID- 29066707
TI  - Fast-Growing Subcutaneous Tumors with Lower-Extremity Edema and Rib Lesions: A
      Case of Non-Hodgkin's Lymphoma in an HIV-1-Infected Patient.
AB  - BACKGROUND Diffuse large B-cell lymphoma (DLBCL) accounts for the large majority
      of AIDS-related non-Hodgkin's lymphoma (NHL). DLBCL usually arises in lymph
      nodes, presenting as a painless rapid swelling mass in the neck, armpit, or
      groin. CASE REPORT Here, we report a case of DLBCL that needed only 3 months to
      develop a tumor 20*15 cm in diameter in the right groin and even caused scrotum
      swelling and lower-extremity edema. Furthermore, this case of DLBCL had developed
      other 3 subcutaneous tumors in the chest wall and their diameters were 16*9 cm,
      7*7 cm, and 3*3 cm. A thoracic computed tomography (CT) scan presented with
      bilateral pleural effusion and the chest wall tumors with rib lesions.
      CONCLUSIONS It is rare that a DLBCL needed only 3 months to develop a tumor 20*15
      cm in diameter and even caused scrotum swelling and unilateral lower-extremity
      edema due to the large mass located in the right groin. Furthermore, it is
      extremely rare that this lymphoma infiltrated the chest wall and even resulted in
      rib lesions.

PMID- 29066708
TI  - Survivorship Analysis of Clinical Adjacent-Segment Pathology After Single-Level
      Cervical Fusion.
AB  - BACKGROUND Clinical adjacent-segment pathology (CASP) is an important problem
      after anterior cervical surgery. The purpose of this study was to predict
      prevalence of CASP and determine the possible risk factors for CASP after single
      level anterior cervical discectomy and fusion surgery. MATERIAL AND METHODS We
      retrospectively reviewed a series of patients who underwent single-level cervical
      discectomy and fusion surgery (ACDF). Both basic and radiographic data of
      patients were collected. Life-table method and Kaplan-Meier analysis were used to
      calculate prevalence of CASP and disease-free survival rate. Cox analysis was
      performed to determine the predictive factors for it. RESULTS A total of 256
      patients were included in this study. The mean length of follow-up was 70.64
      months. Among them, 31 patients were diagnosed as having CASP during follow-up.
      Nineteen of them were at the cephalad adjacent segment, and the other 12 were at
      the caudal segment. After ACDF procedures, 10.01% of patients developed new
      symptoms of CASP within 5 years, and the incidence increased to 23.89% after 10
      years. The incidence rate of CASP was an average of 2.46% per year. Multivariate
      Cox regression analysis showed that congenital stenosis (hazard ratio [HR],
      3.250; 95% confidence interval [CI], 1.538-6.867) and degeneration of adjacent
      segment (HR, 2.681; 95% CI, 1.259-5.709) were correlated with the incidence of
      CASP. CONCLUSIONS Patients with congenital stenosis and pre-existing degenerative
      changes of adjacent segments had a higher risk of developing CASP after single
      level anterior cervical discectomy and fusion.

PMID- 29066709
TI  - [Indirect methods to estimate hidden population].
AB  - Estimating the prevalence of the so-called "hidden populations" can be
      challenging, because the identification of its members is difficult due to their
      socially sanctionable or illegal behaviors. This article provides a critical
      review of the most widely used methods for estimating the size of a hard-to-reach
      population. All are indirect methods, based on incomplete data sources. Depending
      on the available data, one method can be more appropriate than another. Besides,
      each method must fulfill a number of requirements, and each one may be subject to
      specific risk of bias. To choose the most suitable method, an accurate evaluation
      of the available data is necessary, and. if possible several methods should be
      used simultaneously to be able to compare the results and to critically evaluate
      if these results fit with the reality.

PMID- 29066710
TI  - Citizen science provides a reliable and scalable tool to track disease-carrying
      mosquitoes.
AB  - Recent outbreaks of Zika, chikungunya and dengue highlight the importance of
      better understanding the spread of disease-carrying mosquitoes across multiple
      spatio-temporal scales. Traditional surveillance tools are limited by
      jurisdictional boundaries and cost constraints. Here we show how a scalable
      citizen science system can solve this problem by combining citizen scientists'
      observations with expert validation and correcting for sampling effort. Our
      system provides accurate early warning information about the Asian tiger mosquito
      (Aedes albopictus) invasion in Spain, well beyond that available from traditional
      methods, and vital for public health services. It also provides estimates of
      tiger mosquito risk comparable to those from traditional methods but more
      directly related to the human-mosquito encounters that are relevant for
      epidemiological modelling and scalable enough to cover the entire country. These
      results illustrate how powerful public participation in science can be and
      suggest citizen science is positioned to revolutionize mosquito-borne disease
      surveillance worldwide.

PMID- 29066711
TI  - Actomyosin pulsation and flows in an active elastomer with turnover and network
      remodeling.
AB  - Tissue remodeling requires cell shape changes associated with pulsation and flow
      of the actomyosin cytoskeleton. Here we describe the hydrodynamics of actomyosin
      as a confined active elastomer with turnover of its components. Our treatment is
      adapted to describe the diversity of contractile dynamical regimes observed in
      vivo. When myosin-induced contractile stresses are low, the deformations of the
      active elastomer are affine and exhibit spontaneous oscillations, propagating
      waves, contractile collapse and spatiotemporal chaos. We study the nucleation,
      growth and coalescence of actomyosin-dense regions that, beyond a threshold,
      spontaneously move as a spatially localized traveling front. Large myosin-induced
      contractile stresses lead to nonaffine deformations due to enhanced actin and
      crosslinker turnover. This results in a transient actin network that is
      constantly remodeling and naturally accommodates intranetwork flows of the
      actomyosin-dense regions. We verify many predictions of our study in Drosophila
      embryonic epithelial cells undergoing neighbor exchange during germband
      extension.

PMID- 29066713
TI  - Hallucinations in borderline personality disorder: Prevalence, characteristics
      and associations with comorbid symptoms and disorders.
AB  - To establish the point prevalence of hallucinations in borderline personality
      disorder (BPD), telephone interviews were conducted with 324 outpatients
      diagnosed with BPD. Then a subgroup (n = 98) was interviewed in person to
      investigate the co-occurrence of these phenomena with other psychotic symptoms,
      comorbid psychiatric disorders, prior childhood adversities, and adult life
      stressors. For hallucinations in general a point prevalence of 43% was found,
      with rates for hallucinations in separate sensory modalities ranging from 8-21%.
      Auditory verbal hallucinations consisted mostly of verbal abuse and were
      generally experienced as distressing. A significant association was found between
      the severity of hallucinations on the one hand, and delusions and unusual thought
      content on the other; this association was absent for negative symptoms and
      disorganization. The presence of hallucinations also correlated with the number
      of comorbid psychiatric disorders, and with posttraumatic stress disorder (PTSD)
      specifically. Childhood emotional abuse and adult life stressors were also
      associated with hallucinations. The latter three associations suggest that
      patients with BPD might have an etiological mechanism in common with other
      patient/nonpatient groups who experience hallucinations. Based on these findings,
      we advise to treat PTSD and hallucinations when found to be present in patients
      with BPD.

PMID- 29066712
TI  - Activation of STAT3 integrates common profibrotic pathways to promote fibroblast
      activation and tissue fibrosis.
AB  - Signal transducer and activator of transcription 3 (STAT3) is phosphorylated by
      various kinases, several of which have been implicated in aberrant fibroblast
      activation in fibrotic diseases including systemic sclerosis (SSc). Here we show
      that profibrotic signals converge on STAT3 and that STAT3 may be an important
      molecular checkpoint for tissue fibrosis. STAT3 signaling is hyperactivated in
      SSc in a TGFbeta-dependent manner. Expression profiling and functional studies in
      vitro and in vivo demonstrate that STAT3 activation is mediated by the combined
      action of JAK, SRC, c-ABL, and JNK kinases. STAT3-deficient fibroblasts are less
      sensitive to the pro-fibrotic effects of TGFbeta. Fibroblast-specific knockout of
      STAT3, or its pharmacological inhibition, ameliorate skin fibrosis in
      experimental mouse models. STAT3 thus integrates several profibrotic signals and
      might be a core mediator of fibrosis. Considering that several STAT3 inhibitors
      are currently tested in clinical trials, STAT3 might be a candidate for molecular
      targeted therapies of SSc.

PMID- 29066715
TI  - A deterministic detector for vector vortex states.
AB  - Encoding information in high-dimensional degrees of freedom of photons has led to
      new avenues in various quantum protocols such as communication and information
      processing. Yet to fully benefit from the increase in dimension requires a
      deterministic detection system, e.g., to reduce dimension dependent photon loss
      in quantum key distribution. Recently, there has been a growing interest in using
      vector vortex modes, spatial modes of light with entangled degrees of freedom, as
      a basis for encoding information. However, there is at present no method to
      detect these non-separable states in a deterministic manner, negating the benefit
      of the larger state space. Here we present a method to deterministically detect
      single photon states in a four dimensional space spanned by vector vortex modes
      with entangled polarisation and orbital angular momentum degrees of freedom. We
      demonstrate our detection system with vector vortex modes from the |[Formula: see
      text]| = 1 and |[Formula: see text]| = 10 subspaces using classical and weak
      coherent states and find excellent detection fidelities for both pure and
      superposition vector states. This work opens the possibility to increase the
      dimensionality of the state-space used for encoding information while maintaining
      deterministic detection and will be invaluable for long distance classical and
      quantum communication.

PMID- 29066714
TI  - Functional reconstruction of a eukaryotic-like E1/E2/(RING) E3 ubiquitylation
      cascade from an uncultured archaeon.
AB  - The covalent modification of protein substrates by ubiquitin regulates a diverse
      range of critical biological functions. Although it has been established that
      ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is
      less clear how complex eukaryotic ubiquitylation system arose and diversified
      from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like
      and small-RING finger (srfp) protein components in the Aigarchaeota and the
      Asgard archaea superphyla has provided a substantive step toward addressing this
      evolutionary question. Encoded in operons, these components are likely
      representative of the progenitor apparatus that founded the modern eukaryotic
      ubiquitin modification systems. Here we report that these proteins from the
      archaeon Candidatus 'Caldiarchaeum subterraneum' operate together as a bona fide
      ubiquitin modification system, mediating a sequential ubiquitylation cascade
      reminiscent of the eukaryotic process. Our observations support the hypothesis
      that complex eukaryotic ubiquitylation signalling pathways have developed from
      compact systems originally inherited from an archaeal ancestor.

PMID- 29066716
TI  - Vector characterization of zero-order terahertz Bessel beams with linear and
      circular polarizations.
AB  - As a kind of special beams, Bessel beams are always a research hot spot in optics
      due to its non-diffractive and self-healing properties. Here, zero-order
      terahertz (THz) Bessel beams with linear and circular polarizations are generated
      by using a THz quarter wave plate and Teflon axicons with different opening
      angles. By applying a THz digital holographic imaging system, the evolutions of
      the transverse (E x , E y ) and longitudinal (E z ) electric fields are
      coherently measured and analyzed during the propagation processes of the THz
      Bessel beams. The vectorial Rayleigh diffraction integral is used to accurately
      reproduce the amplitude, phase, and non-diffractive feature of each polarization
      component for the THz Bessel beams. With varying opening angles of the axicons,
      the focal spots, diffraction-free ranges, and Gouy phase shifts of the THz Bessel
      beams are compared and discussed. The experiment and simulation results provide a
      comprehensive view for exactly understanding peculiar features of THz Bessel
      beams.

PMID- 29066717
TI  - Establishment and Validation of a Prediction Equation to Estimate Risk of
      Intraoperative Hypothermia in Patients Receiving General Anesthesia.
AB  - Inadvertent intraoperative hypothermia (core temperature <36  degrees C) is a
      frequent but preventable complication of general anesthesia. Accurate risk
      assessment of individual patients may help physicians identify patients at risk
      for hypothermia and apply preventive approaches, which include active
      intraoperative warming. This study aimed to develop and validate a risk
      prediction model for intraoperative hypothermia. Two independent observational
      studies in China, the Beijing Regional Survey and the China National Survey, were
      conducted in 2013 and 2014, respectively, to determine the incidence of
      hypothermia and its underlying risk factors. In this study, using data from these
      two studies, we first derived a risk calculation equation, estimating the
      predictive risk of hypothermia using National Survey data (3132 patients), then
      validated the equation using the Beijing Regional Survey data (830 patients).
      Measures of accuracy, discrimination and calibration were calculated in the
      validation data set. Through validation, this model, named Predictors Score, had
      sound overall accuracy (Brier Score = 0.211), good discrimination (C-Statistic =
      0.759) and excellent calibration (Hosmer-Lemeshow, P = 0.5611). We conclude that
      the Predictors Score is a valid predictor of the risk of operative hypothermia
      and can be used in deciding whether intraoperative warming is a cost-effective
      measure in preventing the hypothermia.

PMID- 29066720
TI  - Chiral transcription in self-assembled tetrahedral Eu4L6 chiral cages displaying
      sizable circularly polarized luminescence.
AB  - Predictable stereoselective formation of supramolecular assembly is generally
      believed to be an important but complicated process. Here, we show that point
      chirality of a ligand decisively influences its supramolecular assembly behavior.
      We designed three closely related chiral ligands with different point
      chiralities, and observe their self-assembly into europium (Eu) tetrametallic
      tetrahedral cages. One ligand exhibits a highly diastereoselective assembly into
      homochiral (either DeltaDeltaDeltaDelta or LambdaLambdaLambdaLambda) Eu
      tetrahedral cages whereas the two other ligands, with two different approaches of
      loosened point chirality, lead to a significant breakdown of the
      diastereoselectivity to generate a mixture of (DeltaDeltaDeltaDelta and
      LambdaLambdaLambdaLambda) isomers. The cages are highly emissive (luminescence
      quantum yields of 16(1) to 18(1)%) and exhibit impressive circularly polarized
      luminescence properties (|g lum|: up to 0.16). With in-depth studies, we present
      an example that correlates the nonlinear enhancement of the chiroptical response
      to the nonlinearity dependence on point chirality.

PMID- 29066718
TI  - Hyperlipidemia-induced cholesterol crystal production by endothelial cells
      promotes atherogenesis.
AB  - Endothelial cells (EC) play a key role in atherosclerosis. Although EC are in
      constant contact with low density lipoproteins (LDL), how EC process LDL and
      whether this influences atherogenesis, is unclear. Here we show that EC take up
      and metabolize LDL, and when overburdened with intracellular cholesterol,
      generate cholesterol crystals (CC). The CC are deposited on the basolateral side,
      and compromise endothelial function. When hyperlipidemic mice are given a high
      fat diet, CC appear in aortic sinus within 1 week. Treatment with cAMP-enhancing
      agents, forskolin/rolipram (F/R), mitigates effects of CC on endothelial function
      by not only improving barrier function, but also inhibiting CC formation both in
      vitro and in vivo. A proof of principle study using F/R incorporated into
      liposomes, designed to target inflamed endothelium, shows reduced atherosclerosis
      and CC formation in ApoE -/- mice. Our findings highlight an important mechanism
      by which EC contribute to atherogenesis under hyperlipidemic conditions.

PMID- 29066721
TI  - Multiscale modelling the effects of CI genetic evolution in mosquito population
      on the control of dengue fever.
AB  - Endosymbiotic Wolbachia bacteria are widely applied for the control of dengue
      fever by manipulating the reproductive mechanism of mosquitoes, including
      maternal inheritance and cytoplasmic incompatibility (CI). CI means that the
      offsprings from the matings between Wolbachia infected males and uninfected
      females can not be hatched. At present, CI effect is assumed as a constant in
      most of dynamic systems for the spread of Wolbachia. However, their spread may
      arouse the evolution of mosquitoes to resist CI. Thus, a multiscale model
      combining a birth-pulse model with a gene-induced discrete model for the
      frequencies of alleles is proposed to describe the spread of Wolbachia in
      mosquito population with resistance allele of CI. The main results indicate that
      the strategy of population eradication can not be realized, while the strategy of
      population replacement may be realized with the success of sensitive or
      resistance allele. If appropriate Wolbachia strains can not be selected, then
      there is a high probability of the failure of population replacement. Moreover,
      Wolbachia-induced parameters may arouse the catastrophic shifts among stable
      states of the model. In addition, the demographic parameters and Wolbachia
      induced parameters may affect the level and the speed of population replacement
      and the density of uninfected mosquitoes.

PMID- 29066719
TI  - Gene isoforms as expression-based biomarkers predictive of drug response in
      vitro.
AB  - Next-generation sequencing technologies have recently been used in
      pharmacogenomic studies to characterize large panels of cancer cell lines at the
      genomic and transcriptomic levels. Among these technologies, RNA-sequencing
      enable profiling of alternatively spliced transcripts. Given the high frequency
      of mRNA splicing in cancers, linking this feature to drug response will open new
      avenues of research in biomarker discovery. To identify robust transcriptomic
      biomarkers for drug response across studies, we develop a meta-analytical
      framework combining the pharmacological data from two large-scale drug screening
      datasets. We use an independent pan-cancer pharmacogenomic dataset to test the
      robustness of our candidate biomarkers across multiple cancer types. We further
      analyze two independent breast cancer datasets and find that specific isoforms of
      IGF2BP2, NECTIN4, ITGB6, and KLHDC9 are significantly associated with AZD6244,
      lapatinib, erlotinib, and paclitaxel, respectively. Our results support isoform
      expressions as a rich resource for biomarkers predictive of drug response.

PMID- 29066723
TI  - Blue-light induced biosynthesis of ROS contributes to the signaling mechanism of
      Arabidopsis cryptochrome.
AB  - Cryptochromes are evolutionarily conserved blue light receptors with many roles
      throughout plant growth and development. They undergo conformational changes in
      response to light enabling interaction with multiple downstream signaling
      partners. Recently, it has been shown that cryptochromes also synthesize reactive
      oxygen species (ROS) in response to light, suggesting the possibility of an
      alternate signaling mechanism. Here we show by fluorescence imaging and
      microscopy that H202 and ROS accumulate in the plant nucleus after cryptochrome
      activation. They induce ROS-regulated transcripts including for genes implicated
      in pathogen defense, biotic and abiotic stress. Mutant cryptochrome alleles that
      are non-functional in photomorphogenesis retain the capacity to induce ROS
      responsive phenotypes. We conclude that nuclear biosynthesis of ROS by
      cryptochromes represents a new signaling paradigm that complements currently
      known mechanisms. This may lead to novel applications using blue light induced
      oxidative bursts to prime crop plants against the deleterious effects of
      environmental stresses and toxins.

PMID- 29066724
TI  - Structural basis for the bacterial membrane insertion of dermcidin peptide, DCD
      1L.
AB  - Human dermcidin (DCD) is an antimicrobial peptide secreted constitutively by
      sweat glands. The anionic derivative, DCD-1L, comprises of the N-terminal 47
      residues of DCD and one additional leucine residue. A previous NMR structure of
      DCD-1L in 50% TFE showed a partial helical conformation, and its crystal
      structure in the presence of Zn2+ outlined a hexameric linear alpha-helical
      bundle. Three different models to describe membrane insertion were proposed but
      no conclusion was drawn. In the current study, the NMR structure of DCD-1L in SDS
      micelles showed an "L-shaped" molecule with three fully formed alpha-helices
      connected by flexible turns. Formation of these helices in DCD-1L in the presence
      of POPG vesicles suggests that the acidic C-terminal region of DCD-1L can
      suppress the binding of DCD-1L to POPG vesicles at basic but not acidic pH.
      Mutation of charged residues on the N-terminal and C-terminal regions of DCD-1L
      cause differences in POPG binding, suggesting distinct functional roles for these
      two regions. Charged residues from these two regions are also found to
      differentially affect Zn2+ coordination and aggregation of DCD-1L in the absence
      or presence of SDS, as monitored by 1D NMR. Our data agrees with one of the three
      models proposed.

PMID- 29066725
TI  - Heparan sulfate: Resilience factor and therapeutic target for cocaine abuse.
AB  - Substance abuse is a pressing problem with few therapeutic options. The
      identification of addiction resilience factors is a potential strategy to
      identify new mechanisms that can be targeted therapeutically. Heparan sulfate
      (HS) is a linear sulfated polysaccharide that is a component of the cell surface
      and extracellular matrix. Heparan sulfate modulates the activity and distribution
      of a set of negatively charged signaling peptides and proteins - known as the HS
      interactome - by acting as a co-receptor or alternative receptor for growth
      factors and other signaling peptides and sequestering and localizing them, among
      other actions. Here, we show that stimulants like cocaine and methamphetamine
      greatly increase HS content and sulfation levels in the lateral hypothalamus and
      that HS contributes to the regulation of cocaine seeking and taking. The ability
      of the HS-binding neuropeptide glial-cell-line-derived neurotrophic factor (GDNF)
      to increase cocaine intake was potentiated by a deletion that abolished its HS
      binding. The delivery of heparanase, the endo-beta-D-glucuronidase that degrades
      HS, accelerated the acquisition of cocaine self-administration and promoted
      persistent responding during extinction. Altogether, these results indicate that
      HS is a resilience factor for cocaine abuse and a novel therapeutic target for
      the treatment of cocaine addiction.

PMID- 29066726
TI  - Cytocompatibility and antibacterial activity of nanostructured H2Ti5O11.H2O
      outlayered Zn-doped TiO2 coatings on Ti for percutaneous implants.
AB  - To improve skin-integration and antibacterial activity of percutaneous implants,
      the coatings comprising an outer layer of H2Ti5O11.H2O (HTO) nanoarrays and an
      inner layer of microporous Zn-doped TiO2 were fabricated on Ti by micro-arc
      oxidation (MAO) followed with hydrothermal treatment (HT). During HT process, a
      large proportion of Zn2+ migrated out from TiO2 layer. TiO2 reacted with OH- and
      H2O, resulting in the nucleation of HTO. The nuclei grew to nanoplates, nanorods
      and nanofibres with HT process prolonged. Simultaneously, the orientation of
      nanoarrays changed from quasi-vertical to parallel to substrate. Compared to Ti,
      adhesion and proliferation of fibroblasts were enhanced on as-MAOed TiO2 and HTed
      coatings. The phenotype, differentiation and extracellular collagen secretion
      were obviously accelerated on vertical nanorods with proper interspace (e.g. 63
      nm). HTed coatings showed enhanced antibacterial activity, which should be
      ascribed to the nano-topography of HTO.

PMID- 29066722
TI  - BCL-XL directly modulates RAS signalling to favour cancer cell stemness.
AB  - In tumours, accumulation of chemoresistant cells that express high levels of anti
      apoptotic proteins such as BCL-XL is thought to result from the counter selection
      of sensitive, low expresser clones during progression and/or initial treatment.
      We herein show that BCL-XL expression is selectively advantageous to cancer cell
      populations even in the absence of pro-apoptotic pressure. In transformed human
      mammary epithelial cells BCL-XL favours full activation of signalling downstream
      of constitutively active RAS with which it interacts in a BH4-dependent manner.
      Comparative proteomic analysis and functional assays indicate that this is
      critical for RAS-induced expression of stemness regulators and maintenance of a
      cancer initiating cell (CIC) phenotype. Resistant cancer cells thus arise from a
      positive selection driven by BCL-XL modulation of RAS-induced self-renewal, and
      during which apoptotic resistance is not necessarily the directly selected trait.

PMID- 29066727
TI  - Affecting long-term fear memory formation through optical control of Rac1 GTPase
      and PAK activity in lateral amygdala.
AB  - Fear conditioning, a behavioral model for studying fear-related disorders, is
      believed to be formed by alterations of synaptic efficacy mediated by changes in
      synaptic transmission and neuronal morphology in lateral amygdala (LA). Rac
      GTPase and its downstream effector p21-activated kinase (PAK) are involved in
      such key neuronal functions. Here we show that optical activation of Rac1 GTPase
      using photoactivatable form of Rac1 (PA-Rac1) in amygdala led to phosphorylation
      of PAK and inhibition of long-term but not short-term auditory fear conditioning
      memory formation. Activation of PA-Rac1 in LA one day after fear conditioning had
      no effect on long-term fear memory tested 24 hrs after PA-Rac1 activation.
      Inhibition of PAK in LA by microinjection of the PAK inhibitor IPA-3 30 minutes
      before fear conditioning enhanced long-term but not short-term fear memory
      formation. Our results demonstrate that photoactivation of Rac1 GTPase in lateral
      amygdala impairs fear memory formation. Moreover, Rac1 effector PAK activity
      during fear conditioning constrains the formation of fear memory in LA. Thus, Rac
      GTPase and PAK proteins may serve as targets for treatment of fear and anxiety
      disorders.

PMID- 29066728
TI  - Ghrelin rescues skeletal muscle catabolic profile in the R6/2 mouse model of
      Huntington's disease.
AB  - Accumulating evidence suggests altered energy metabolism as a key feature in
      Huntington's disease (HD) pathology. Hyper-catabolism, including weight loss and
      muscle atrophy, is seen in HD patients and HD mouse models. Metabolic hormones
      are key players, not only in energy metabolism, but also in neurodegenerative
      processes. Ghrelin, a gut peptide-hormone, plays an important role in regulating
      energy metabolism, stimulating appetite, and affects brain function and increases
      neuronal survival. The R6/2 mouse model of HD has previously been shown to
      exhibit progressive weight loss, dysregulated glucose metabolism, skeletal muscle
      atrophy and altered body composition. In this study, we targeted energy
      metabolism in R6/2 mice using ghrelin administration, with the primary aim to
      delay weight loss and reduce muscle atrophy. We also evaluated glucose metabolism
      and behaviour. We here demonstrate that ghrelin administration (subcutaneous 150
      MUg/kg daily injections) for 4 weeks, reversed the catabolic gene expression
      profile (increased expression of Caspase 8, Traf-5 and Creb1) seen in R6/2 mouse
      skeletal muscle. Skeletal muscle morphology was also improved with ghrelin, and
      importantly, ghrelin administration normalized behavioural deficits in R6/2 mice.
      Taken together, our findings encourage further studies targeting metabolism in
      HD.

PMID- 29066729
TI  - A quantitative model of the phytochrome-PIF light signalling initiating
      chloroplast development.
AB  - The components required for photosynthesis are encoded in two separate genomes,
      the nuclear and the plastid. To address how synchronization of the two genomes
      involved can be attained in early light-signalling during chloroplast development
      we have formulated and experimentally tested a mathematical model simulating
      light sensing and the following signalling response. The model includes
      phytochrome B (PhyB), the phytochrome interacting factor 3 (PIF3) and putative
      regulatory targets of PIF3. Closed expressions of the phyB and PIF3
      concentrations after light exposure are derived, which capture the relevant
      timescales in the response of genes regulated by PIF3. Sequence analysis
      demonstrated that the promoters of the nuclear genes encoding sigma factors
      (SIGs) and polymerase-associated proteins (PAPs) required for expression of
      plastid encoded genes, contain the cis-elements for binding of PIF3. The model
      suggests a direct link between light inputs via PhyB-PIF3 to the plastid
      transcription machinery and control over the expression of photosynthesis
      components both in the nucleus and in the plastids. Using a pluripotent
      Arabidopsis cell culture in which chloroplasts develop from undifferentiated
      proplastids following exposure to light, we could experimentally verify that the
      expression of SIGs and PAPs in response to light follow the calculated expression
      of a PhyB-PIF3 regulated gene.

PMID- 29066730
TI  - Neutrophil-lymphocyte Ratio Plus Prognostic Nutritional Index Predicts the
      Outcomes of Patients with Unresectable Hepatocellular Carcinoma After
      Transarterial Chemoembolization.
AB  - For many malignancies, inflammation-based scores correlate with survival. The
      neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) are
      immunonutritional indices associated with postoperative outcomes in patients with
      hepatocellular carcinoma (HCC). We evaluated whether a combined preoperative NLR
      and PNI score was prognostically superior to either index alone in 793 patients
      with unresectable HCC after transarterial chemoembolization. Patient demographic,
      clinical, and pathological data were also collected and analysed. A receiver
      operating characteristic (ROC) analysis was used to classify patients as follows:
      NLR-PNI 0 group (NLR <= 2.2 and PNI > 46), NLR-PNI 1 group (NLR > 2.2 or PNI <=
      46) and NLR-PNI 2 group (NLR > 2.2 and PNI <= 46). Regarding 1-, 3-, and 5-year
      survival, the NLR-PNI score had superior discriminative abilities (i.e., higher
      area under the ROC curve), compared with either the NLR or PNI alone, and
      patients in the NLR-PNI 0, 1, and 2 groups had median survival times of 33 (95%
      confidence interval: 22.8-43.2), 14 (10.9-17.1), and 6 (9.9-14.1) months,
      respectively. In multivariate analyses, the Barcelona Clinic Liver Cancer, total
      bilirubin, vascular invasion, and NLR-PNI score adversely affected overall
      survival. In conclusion, the NLR-PNI score can improve the accuracy of prognoses
      for patients with unresectable HCC.

PMID- 29066731
TI  - Discriminative Prior - Prior Image Constrained Compressed Sensing Reconstruction
      for Low-Dose CT Imaging.
AB  - X-ray computed tomography (CT) has been widely used to provide patient-specific
      anatomical information in the forms of tissue attenuation. However, the
      cumulative radiation induced in CT scan has raised extensive concerns in recently
      years. How to maintain reconstruction image quality is a major challenge for low
      dose CT (LDCT) imaging. Generally, LDCT imaging can be greatly improved by
      incorporating prior knowledge in some specific forms. A joint estimation
      framework termed discriminative prior-prior image constrained compressed sensing
      (DP-PICCS) reconstruction is proposed in this paper. This DP-PICCS algorithm
      utilizes discriminative prior knowledge via two feature dictionary constraints
      which built on atoms from the samples of tissue attenuation feature patches and
      noise-artifacts residual feature patches, respectively. Also, the prior image
      construction relies on a discriminative feature representation (DFR) processing
      by two feature dictionary. Its comparison to other competing methods through
      experiments on low-dose projections acquired from torso phantom simulation study
      and clinical abdomen study demonstrated that the DP-PICCS method achieved
      promising improvement in terms of the effectively-suppressed noise and the well
      retained structures.

PMID- 29066732
TI  - Associations between genetic risk variants for kidney diseases and kidney disease
      etiology.
AB  - Chronic kidney disease (CKD) is a global health problem with a genetic component.
      Genome-wide association studies have identified variants associated with specific
      CKD etiologies, but their genetic overlap has not been well studied. This study
      examined SNP associations across different CKD etiologies and CKD stages using
      data from 5,034 CKD patients of the German Chronic Kidney Disease study. In
      addition to confirming known associations, a systemic lupus erythematosus
      associated risk variant at TNXB was also associated with CKD attributed to type 1
      diabetes (p = 2.5 * 10-7), a membranous nephropathy-associated variant at HLA
      DQA1 was also associated with CKD attributed to systemic lupus erythematosus (p =
      5.9 * 10-6), and an IgA risk variant at HLA-DRB1 was associated with both CKD
      attributed to granulomatosis with polyangiitis (p = 2.0 * 10-4) and to type 1
      diabetes (p = 4.6 * 10-11). Associations were independent of additional risk
      variants in the respective genetic regions. Evaluation of CKD stage showed a
      significant association of the UMOD risk variant, previously identified in
      population-based studies for association with kidney function, for advanced
      (stage >=G3b) compared to early-stage CKD (<=stage G2). Shared genetic
      associations across CKD etiologies and stages highlight the role of the immune
      response in CKD. Association studies with detailed information on CKD etiology
      can reveal shared genetic risk variants.

PMID- 29066733
TI  - Adaptive combination of Bayes factors as a powerful method for the joint analysis
      of rare and common variants.
AB  - Multi-marker association tests can be more powerful than single-locus analyses
      because they aggregate the variant information within a gene/region. However,
      combining the association signals of multiple markers within a gene/region may
      cause noise due to the inclusion of neutral variants, which usually compromises
      the power of a test. To reduce noise, the "adaptive combination of P-values"
      (ADA) method removes variants with larger P-values. However, when both rare and
      common variants are considered, it is not optimal to truncate variants according
      to their P-values. An alternative summary measure, the Bayes factor (BF), is
      defined as the ratio of the probability of the data under the alternative
      hypothesis to that under the null hypothesis. The BF quantifies the "relative"
      evidence supporting the alternative hypothesis. Here, we propose an "adaptive
      combination of Bayes factors" (ADABF) method that can be directly applied to
      variants with a wide spectrum of minor allele frequencies. The simulations show
      that ADABF is more powerful than single-nucleotide polymorphism (SNP)-set kernel
      association tests and burden tests. We also analyzed 1,109 case-parent trios from
      the Schizophrenia Trio Genomic Research in Taiwan. Three genes on chromosome
      19p13.2 were found to be associated with schizophrenia at the suggestive
      significance level of 5 * 10-5.

PMID- 29066735
TI  - Large reversible magnetocaloric effect in antiferromagnetic Ho2O3 powders.
AB  - Giant magnetocaloric materials are highly promising for technological
      applications in magnetic refrigeration. Although giant magnetocaloric effects
      were discovered in first-order magnetic transition materials, it is accompanied
      by some non-desirable drawbacks, such as important hysteretic phenomena,
      irreversibility of the effect, or poor mechanical stability, which limits their
      use in applications. Here, we report the discovery of a giant magnetocaloric
      effect in commercialized Ho2O3 oxide at low temperature (around 2 K) without
      hysteresis losses. Ho2O3 is found to exhibit a second-order antiferromagnetic
      transition with a Neel temperature of 2 K. At an applied magnetic field change of
      5 T and below 3.5 K, the maximum value of magnetic entropy change [Formula: see
      text], the refrigerant capacity (RC) were found to be 31.9 J.K-1.kg-1 and 180 J.K
      1, respectively.

PMID- 29066734
TI  - Association of muscle lipidomic profile with high-fat diet-induced insulin
      resistance across five mouse strains.
AB  - Different mouse strains exhibit variation in their inherent propensities to
      develop metabolic disease. We recently showed that C57BL6, 129X1, DBA/2 and FVB/N
      mice are all susceptible to high-fat diet-induced glucose intolerance, while
      BALB/c mice are relatively protected, despite changes in many factors linked with
      insulin resistance. One parameter strongly linked with insulin resistance is
      ectopic lipid accumulation, especially metabolically active ceramides and
      diacylglycerols (DAG). This study examined diet-induced changes in the skeletal
      muscle lipidome across these five mouse strains. High-fat feeding increased total
      muscle triacylglycerol (TAG) content, with elevations in similar triacylglycerol
      species observed for all strains. There were also generally consistent changes
      across strains in the abundance of different phospholipid (PL) classes and the
      fatty acid profile of phospholipid molecular species, with the exception being a
      strain-specific difference in phospholipid species containing two polyunsaturated
      fatty acyl chains in BALB/c mice (i.e. a diet-induced decrease in the other four
      strains, but no change in BALB/c mice). In contrast to TAG and PL, the high-fat
      diet had a minor influence on DAG and ceramide species across all strains. These
      results suggest that widespread alterations in muscle lipids are unlikely a major
      contributors to the favourable metabolic profile of BALB/c mice and rather there
      is a relatively conserved high-fat diet response in muscle of most mouse strains.

PMID- 29066736
TI  - Enhanced ice sheet melting driven by volcanic eruptions during the last
      deglaciation.
AB  - Volcanic eruptions can impact the mass balance of ice sheets through changes in
      climate and the radiative properties of the ice. Yet, empirical evidence
      highlighting the sensitivity of ancient ice sheets to volcanism is scarce. Here
      we present an exceptionally well-dated annual glacial varve chronology recording
      the melting history of the Fennoscandian Ice Sheet at the end of the last
      deglaciation (~13,200-12,000 years ago). Our data indicate that abrupt ice
      melting events coincide with volcanogenic aerosol emissions recorded in Greenland
      ice cores. We suggest that enhanced ice sheet runoff is primarily associated with
      albedo effects due to deposition of ash sourced from high-latitude volcanic
      eruptions. Climate and snowpack mass-balance simulations show evidence for
      enhanced ice sheet runoff under volcanically forced conditions despite
      atmospheric cooling. The sensitivity of past ice sheets to volcanic ashfall
      highlights the need for an accurate coupling between atmosphere and ice sheet
      components in climate models.

PMID- 29066737
TI  - Response of basal metabolic rate to complete submergence of riparian species
      Salix variegata in the Three Gorges reservoir region.
AB  - One-year old seedlings of Salix variegata (submergence-tolerant) and Cinnamomum
      camphora (submergence-intolerant) were selected and subjected to complete
      submergence (2 m) for 1, 5, 10, and 20 days, to elucidate the submergence-
      tolerance mechanism of S. variegata in the Three Gorges reservoir region. The
      basal CO2 emission ratios (BCERs) and O2 consumption rates (OCRs) of leaf, stem,
      and root were determined. The basal O2 consumption rates (BOCRs) were calculated
      from the OCRs of different parts and their biomass allocations and used for
      evaluating the basal metabolic rate (BMR) of species with BCERs. The results
      showed that: (1) The BCERs of both species responded to flooding similarly, and
      no significant differences occurred between the submerged S. variegata (SS) and
      the submerged C. camphora (SC) seedlings, and between the control S. variegata
      (CS) and the control C. camphora (CC) seedlings. (2) The BOCRs of SS were
      significantly lower than those of SC on days 1 and 20, while no significant
      differences occurred between CS and CC for every duration. Therefore, the BMRs,
      evaluated from BOCRs rather than from BCERs, were related to submergence
      tolerance of species, and the response of BMR to submergence would contribute to
      the survival of S. variegata seedlings under flooding.

PMID- 29066738
TI  - ALK and IGF-1R as independent targets in crizotinib resistant lung cancer.
AB  - ALK positive non-small cell lung cancer is highly responsive to ALK inhibitors
      such as crizotinib, but drug resistance typically develops within a year of
      treatment. In this study we investigated whether IGF-1R is an independent
      druggable target in ALK-positive lung cancer cells. We confirmed that combination
      ALK and IGF-1R inhibitor treatment is synergistically cytotoxic to ALK-positive
      lung cancer cells and that this remains the case for at least 12 days after
      initial exposure to crizotinib. ALK-positive cells with acquired resistance to
      crizotinib did not acquire cross-resistance to IGF-1R inhibition, though
      combination treatment in the resistant cells gave additive rather than
      synergistic cytotoxicity. We concluded that IGF-1R is an independent druggable
      target in ALK-positive lung cancer and support the trial of combination
      treatment.

PMID- 29066739
TI  - Impacts of microhabitat changes on wintering waterbird populations.
AB  - Caisang Lake, a human-modified wetland, experienced dramatic habitat alterations
      from the planting of lotus and culturing of crab. Whether the Caisang Lake still
      maintains populations of wintering waterbirds is of great concern. Here, we
      compare the changes in waterbird populations before and after habitat alterations
      in Caisang Lake and assess the driving factors leading to the dramatic changes in
      waterbird populations. Results indicate that wintering waterbird populations were
      significantly impacted by altered forage availability, with species- and guild
      specific responses. Dramatic habitat alterations from planting lotus caused
      significant declines in areas of native vegetation, mudflats, and water that may
      have caused associated declines in herbivores, insectivores, and fish-eating
      waterbirds, respectively. In contrast, the increased size of the lotus area
      appears to have led to an increase in omnivorous waterbirds. A food shortage,
      potentially caused by a large area of Caisang Lake being used for culturing crab,
      might be another cause of the observed decline in fish-eating waterbirds. This
      study demonstrates a powerful approach to systematically evaluate waterbird
      responses to wetland management policies. These findings are important as efforts
      are made to protect the wintering waterbirds from the effects of human
      intervention, particularly at other Ramsar wetlands.

PMID- 29066740
TI  - TRPC3 Is Dispensable for beta-Alanine Triggered Acute Itch.
AB  - The detection of pruritic (itchy) stimuli is mediated by a variety of receptors
      and channels expressed by primary sensory neurons. The G protein-coupled receptor
      (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic
      nociceptors and functions as the molecular receptor for the itch-inducing
      chemical beta-alanine. However, the channels responsible for generating
      electrical signals downstream of MRGPRD remain unclear. Here, we found that a
      member of the canonical TRP channel family, TRPC3, is highly expressed in MRGPRD+
      non-peptidergic nociceptors, raising the possibility of whether TRPC3 functions
      as a downstream channel in the MRGPRD signaling pathway. We tested TrpC3 null
      mice for beta-alanine induced itch, and found that these mice exhibit normal
      responses to beta-alanine. At the cellular level, calcium influx triggered by
      beta-alanine is also unchanged in cultured DRG neurons from TrpC3 null mice
      compared to wild type. Together, our results demonstrate that mouse TrpC3 is
      dispensable for beta-alanine-induced acute itch.

PMID- 29066741
TI  - Peripheral CD19hi B cells exhibit activated phenotype and functionality in
      promoting IgG and IgM production in human autoimmune diseases.
AB  - Systemic Lupus Erythematosus (SLE) and pemphigus are two representative
      autoimmune diseases driven by pathogenic autoantibody systemically and organ
      specifically, respectively. Given the involvement of antibody in the
      pathogenesis, B cells are inclined to differentiate and function in an abnormal
      activation model. Here we defined a unique CD19hi B cell population existing in
      the periphery of SLE and pemphigus patients as well as in human tonsils. CD19hi B
      cells could be induced in vitro after co-culturing fully activated CD4+ T cells
      with autologous B cells. They expressed high levels of HLA-DR, IgG, IgM and
      multiple ligands of costimulatory molecules with the capacity to produce extra
      IgG and IgM. Transcirptome assay revealed that genes involved in B-cell
      activation and differentiation were up-regulated in CD19hi B cells. Antibody
      blockade experiments showed that the interactions between costimulatory molecules
      contributed to CD19hi B-cell generation and IgG/IgM production. What is more,
      frequencies of peripheral CD19hi B cells from SLE and pemphigus patients were
      correlated with serum total IgG and IgM, but not with autoantigen-specific
      antibodies and disease severity. Therefore, our investigation demonstrates that
      CD19hi B cells might contain B cell precursors for terminal differentiation and
      contribute to total IgG/IgM production in human autoimmune diseases.

PMID- 29066742
TI  - Cardamonin inhibits colonic neoplasia through modulation of MicroRNA expression.
AB  - Colorectal cancer is currently the third leading cause of cancer related deaths.
      There is considerable interest in using dietary intervention strategies to
      prevent chronic diseases including cancer. Cardamonin is a spice derived
      nutraceutical and herein, for the first time we evaluated the therapeutic
      benefits of cardamonin in Azoxymethane (AOM) induced mouse model of colorectal
      cancer. Mice were divided into 4 groups of which three groups were given six
      weekly injections of AOM. One group served as untreated control and remaining
      groups were treated with either vehicle or Cardamonin starting from the same day
      or 16 weeks after the first AOM injection. Cardamonin treatment inhibited the
      tumor incidence, tumor multiplicity, Ki-67 and beta-catenin positive cells. The
      activation of NF-kB signaling was also abrogated after cardamonin treatment. To
      elucidate the mechanism of action a global microRNA profiling of colon samples
      was performed. Computational analysis revealed that there is a differential
      expression of miRNAs between these groups. Subsequently, we extend our findings
      to human colorectal cancer and found that cardamonin inhibited the growth,
      induces cell cycle arrest and apoptosis in human colorectal cancer cell lines.
      Taken together, our study provides a better understanding of chemopreventive
      potential of cardamonin in colorectal cancer.

PMID- 29066744
TI  - Rewinding the waves: tracking underwater signals to their source.
AB  - Analysis of data, recorded on March 8th 2014 at the Comprehensive Nuclear-Test
      Ban Treaty Organisation's hydroacoustic stations off Cape Leeuwin Western
      Australia, and at Diego Garcia, reveal unique pressure signatures that could be
      associated with objects impacting at the sea surface, such as falling meteorites,
      or the missing Malaysian Aeroplane MH370. To examine the recorded signatures, we
      carried out experiments with spheres impacting at the surface of a water tank,
      where we observed almost identical pressure signature structures. While the
      pressure structure is unique to impacting objects, the evolution of the radiated
      acoustic waves carries information on the source. Employing acoustic-gravity wave
      theory we present an analytical inverse method to retrieve the impact time and
      location. The solution was validated using field observations of recent
      earthquakes, where we were able to calculate the eruption time and location to a
      satisfactory degree of accuracy. Moreover, numerical validations confirm an error
      below 0.02% for events at relatively large distances of over 1000 km. The method
      can be developed to calculate other essential properties such as impact duration
      and geometry. Besides impacting objects and earthquakes, the method could help in
      identifying the location of underwater explosions and landslides.

PMID- 29066745
TI  - Mantle hydration along outer-rise faults inferred from serpentinite permeability.
AB  - Recent geophysical surveys indicate that hydration (serpentinization) of oceanic
      mantle is related to outer-rise faulting prior to subduction. The
      serpentinization of oceanic mantle influences the generation of intermediate
      depth earthquakes and subduction water flux, thereby promoting arc volcanism.
      Since the chemical reactions that produce serpentinite are geologically rapid at
      low temperatures, the flux of water delivery to the reaction front appears to
      control the lateral extent of serpentinization. In this study, we measured the
      permeability of low-temperature serpentinites composed of lizardite and
      chrysotile, and calculated the lateral extent of serpentinization along an outer
      rise fault based on Darcy's law. The experimental results indicate that
      serpentinization extends to a region several hundred meters wide in the direction
      normal to the outer-rise fault in the uppermost oceanic mantle. We calculated the
      global water flux carried by serpentinized oceanic mantle ranging from 1.7 * 1011
      to 2.4 * 1012 kg/year, which is comparable or even higher than the water flux of
      hydrated oceanic crust.

PMID- 29066743
TI  - Cytoplasmic cyclin D1 controls the migration and invasiveness of mantle lymphoma
      cells.
AB  - Mantle cell lymphoma (MCL) is a hematologic neoplasm characterised by the
      t(11;14)(q13;q32) translocation leading to aberrant cyclin D1 expression. The
      cell functions of cyclin D1 depend on its partners and/or subcellular
      distribution, resulting in different oncogenic properties. We observed the
      accumulation of cyclin D1 in the cytoplasm of a subset of MCL cell lines and
      primary cells. In primary cells, this cytoplasmic distribution was correlated
      with a more frequent blastoid phenotype. We performed immunoprecipitation assays
      and mass spectrometry on enriched cytosolic fractions from two cell lines. The
      cyclin D1 interactome was found to include several factors involved in adhesion,
      migration and invasion. We found that the accumulation of cyclin D1 in the
      cytoplasm was associated with higher levels of migration and invasiveness. We
      also showed that MCL cells with high cytoplasmic levels of cyclin D1 engrafted
      more rapidly into the bone marrow, spleen, and brain in immunodeficient mice.
      Both migration and invasion processes, both in vivo and in vitro, were
      counteracted by the exportin 1 inhibitor KPT-330, which retains cyclin D1 in the
      nucleus. Our data reveal a role of cytoplasmic cyclin D1 in the control of MCL
      cell migration and invasion, and as a true operator of MCL pathogenesis.

PMID- 29066747
TI  - Automatic recognition of therapy progress among children with autism.
AB  - The article presents a research study on recognizing therapy progress among
      children with autism spectrum disorder. The progress is recognized on the basis
      of behavioural data gathered via five specially designed tablet games. Over 180
      distinct parameters are calculated on the basis of raw data delivered via the
      game flow and tablet sensors - i.e. touch screen, accelerometer and gyroscope.
      The results obtained confirm the possibility of recognizing progress in
      particular areas of development. The recognition accuracy exceeds 80%. Moreover,
      the study identifies a subset of parameters which appear to be better predictors
      of therapy progress than others. The proposed method - consisting of data
      recording, parameter calculation formulas and prediction models - might be
      implemented in a tool to support both therapists and parents of autistic
      children. Such a tool might be used to monitor the course of the therapy, modify
      it and report its results.

PMID- 29066746
TI  - Identification of functional tetramolecular RNA G-quadruplexes derived from
      transfer RNAs.
AB  - RNA G-quadruplex (RG4) structures are involved in multiple biological processes.
      Recent genome-wide analyses of human mRNA transcriptome identified thousands of
      putative intramolecular RG4s that readily assemble in vitro but shown to be
      unfolded in vivo. Previously, we have shown that mature cytoplasmic tRNAs are
      cleaved during stress response to produce tRNA fragments that function to repress
      translation in vivo. Here we report that these bioactive tRNA fragments assemble
      into intermolecular RG4s. We provide evidence for the formation of uniquely
      stable tetramolecular RG4 structures consisting of five tetrad layers formed by
      5'-terminal oligoguanine motifs of an individual tRNA fragment. RG4 is required
      for functions of tRNA fragments in the regulation of mRNA translation, a critical
      component of cellular stress response. RG4 disruption abrogates tRNA fragments
      ability to trigger the formation of Stress Granules in vivo. Collectively, our
      data rationalize the existence of naturally occurring RG4-assembling tRNA
      fragments and emphasize their regulatory roles.

PMID- 29066748
TI  - Complex furrows in a 2D epithelial sheet code the 3D structure of a beetle horn.
AB  - The external organs of holometabolous insects are generated through two
      consecutive processes: the development of imaginal primordia and their subsequent
      transformation into the adult structures. During the latter process, many
      different phenomena at the cellular level (e.g. cell shape changes, cell
      migration, folding and unfolding of epithelial sheets) contribute to the drastic
      changes observed in size and shape. Because of this complexity, the logic behind
      the formation of the 3D structure of adult external organs remains largely
      unknown. In this report, we investigated the metamorphosis of the horn in the
      Japanese rhinoceros beetle Trypoxylus dichotomus. The horn primordia is
      essentially a 2D epithelial cell sheet with dense furrows. We experimentally
      unfolded these furrows using three different methods and found that the furrow
      pattern solely determines the 3D horn structure, indicating that horn formation
      in beetles occurs by two distinct processes: formation of the furrows and
      subsequently unfolding them. We postulate that this developmental simplicity
      offers an inherent advantage to understanding the principles that guide 3D
      morphogenesis in insects.

PMID- 29066749
TI  - Effect of light, gibberellic acid and nitrogen source on germination of eight
      taxa from dissapearing European temperate forest, Potentillo albae-Quercetum.
AB  - Little is known about how light affects seed germination and revegetation of
      species of thermophilous oak forest. To reveal this relationship effects of
      white, red, far-red irradiations and dark incubation on germination of eight
      Potentillo albae-Quercetum taxa were examined. Attempts were also made to
      evaluate the influence of gibberellic acid and different nitrogen sources on the
      germination characteristics. Interaction between light and nitrogen was also
      studied. Freshly matured seeds of all taxa germinated very poorly, indicating
      presence of primary dormancy. Germination rates increased after wet
      stratification treatment and were low in darkness. The highest concentration of
      the nitrogenous solutions that resulted in high germination level was 10 mM,
      whereas higher concentrations had a negative effect. Nitrate had the strongest
      influence which can be proved by a 'gap detection' mechanism for gaps in the
      vegetation. Far-red and red irradiation showed antagonistic effect on seed
      germination. There was a decrease in germination when far-red was followed by red
      and an improvement when red was followed by far-red treatment. Under red light,
      gibberellic acid enhanced germination of positively photoblastic taxa. It was
      concluded that light factor, associated with vegetation gaps, was the most
      important signal stimulating germination of the studied taxa.

PMID- 29066750
TI  - Ontogeny of foraging behaviour in juvenile red-footed boobies (Sula sula).
AB  - The early life stages represent a crucial period that can strongly influence
      population dynamics. We studied the development of foraging behaviour in the red
      footed booby, a tropical seabird with an extensive post-fledging care period (3
      to 6 months). Adults and juveniles were observed from shore and tracked at sea
      using GPS loggers over 3 consecutive 12-day periods. Juveniles initially made a
      majority of flights inland, likely to practice flying, and formed groups of up to
      10 juveniles before making short trips at sea. They left the island later and
      returned earlier than the adults, allowing them to be fed on the nest. Over time,
      juveniles left the colony alone more frequently and increased the range of their
      trips while remaining significantly closer to the colony than the adults. They
      spent more time intensively foraging (slow and sinuous trajectory) than adults,
      which could reflect attempts to capture prey. Juveniles foraged independently of
      their parents but associated frequently with congeners, particularly during area
      restricted search (ARS) behaviour. The extensive post-fledging care period
      observed may be explained by the need to develop proper foraging skills adapted
      to tropical waters, where resources are particularly scarce and unpredictable.

PMID- 29066751
TI  - Revealing the gut bacteriome of Dendroctonus bark beetles (Curculionidae:
      Scolytinae): diversity, core members and co-evolutionary patterns.
AB  - Dendroctonus bark beetles comprise 20 taxonomically recognized species, which are
      one of the most destructive pine forest pests in North and Central America, and
      Eurasia. The aims of this study were to characterize the gut bacterial diversity,
      to determine the core bacteriome and to explore the ecological association
      between these bacteria and bark beetles. A total of five bacterial phyla were
      identified in the gut of 13 Dendroctonus species; Proteobacteria was the most
      abundant, followed by Firmicutes, Fusobacteria, Actinobacteria and Deinococcus
      Thermus. The alpha-diversity was low as demonstrated in previous studies and
      significant differences in beta-diversity were observed. The core bacteriome was
      composed of Enterobacter, Pantoea, Pseudomonas, Rahnella, Raoultella, and
      Serratia. The tanglegram between bacteria and bark beetles suggests that members
      of bacterial community are acquired from the environment, possibly from the host
      tree. These findings improve the knowledge about the bacterial community
      composition, and provide the bases to study the metabolic functions of these
      bacteria, as well as their interaction with these bark beetles.

PMID- 29066752
TI  - Conformational stabilization as a strategy to prevent nucleophosmin
      mislocalization in leukemia.
AB  - Nucleophosmin (NPM) is a nucleolar protein involved in ribosome assembly and cell
      homeostasis. Mutations in the C-terminal domain of NPM that impair native folding
      and localization are associated with acute myeloid leukemia (AML). We have
      performed a high-throughput screening searching for compounds that stabilize the
      C-terminal domain. We identified three hit compounds which show the ability to
      increase the thermal stability of both the C-terminal domain as well as full
      length NPM. The best hit also seemed to favor folding of an AML-like mutant.
      Computational pocket identification and molecular docking support a stabilization
      mechanism based on binding of the phenyl/benzene group of the compounds to a
      particular hydrophobic pocket and additional polar interactions with solvent
      accessible residues. Since these results indicate a chaperoning potential of our
      candidate hits, we tested their effect on the subcellular localization of AML
      like mutants. Two compounds partially alleviated the aggregation and restored
      nucleolar localization of misfolded mutants. The identified hits appear promising
      as pharmacological chaperones aimed at therapies for AML based on conformational
      stabilization of NPM.

PMID- 29066754
TI  - Fungal community structure of fallen pine and oak wood at different stages of
      decomposition in the Qinling Mountains, China.
AB  - Historically, intense forest hazards have resulted in an increase in the quantity
      of fallen wood in the Qinling Mountains. Fallen wood has a decisive influence on
      the nutrient cycling, carbon budget and ecosystem biodiversity of forests, and
      fungi are essential for the decomposition of fallen wood. Moreover, decaying dead
      wood alters fungal communities. The development of high-throughput sequencing
      methods has facilitated the ongoing investigation of relevant molecular forest
      ecosystems with a focus on fungal communities. In this study, fallen wood and its
      associated fungal communities were compared at different stages of decomposition
      to evaluate relative species abundance and species diversity. The physical and
      chemical factors that alter fungal communities were also compared by performing
      correspondence analysis according to host tree species across all stages of
      decomposition. Tree species were the major source of differences in fungal
      community diversity at all decomposition stages, and fungal communities achieved
      the highest levels of diversity at the intermediate and late decomposition
      stages. Interactions between various physical and chemical factors and fungal
      communities shared the same regulatory mechanisms, and there was no tree species
      specific influence. Improving our knowledge of wood-inhabiting fungal communities
      is crucial for forest ecosystem conservation.

PMID- 29066753
TI  - Fine control of chlorophyll-carotenoid interactions defines the functionality of
      light-harvesting proteins in plants.
AB  - Photosynthetic antenna proteins can be thought of as "programmed solvents", which
      bind pigments at specific mutual orientations, thus tuning the overall energetic
      landscape and ensuring highly efficient light-harvesting. While positioning of
      chlorophyll cofactors is well understood and rationalized by the principle of an
      "energy funnel", the carotenoids still pose many open questions. Particularly,
      their short excited state lifetime (<25 ps) renders them potential energy sinks
      able to compete with the reaction centers and drastically undermine light
      harvesting efficiency. Exploration of the orientational phase-space revealed that
      the placement of central carotenoids minimizes their interaction with the nearest
      chlorophylls in the plant antenna complexes LHCII, CP26, CP29 and LHCI. At the
      same time we show that this interaction is highly sensitive to structural
      perturbations, which has a profound effect on the overall lifetime of the
      complex. This links the protein dynamics to the light-harvesting regulation in
      plants by the carotenoids.

PMID- 29066756
TI  - Near-infrared photothermal/photodynamic therapy with indocyanine green induces
      apoptosis of hepatocellular carcinoma cells through oxidative stress.
AB  - Indocyanine green (ICG) is a photothermal agent, photosensitizer, and
      fluorescence imaging probe which shows specific accumulation in hepatocellular
      carcinoma (HCC) cells. We recently developed a photodynamic therapy (PDT) using
      ICG and near-infrared (NIR) laser as a new anti-cancer treatment for HCC.
      However, the molecular mechanism underlying this effect needs to be elucidated.
      HuH-7 cells, a well-differentiated human HCC cell line, were transplanted
      subcutaneously into BALB/c-nu/nu mice for in vivo experiment. ICG was
      administered 24 h before NIR irradiation. The irradiation was performed at three
      tumor locations by 823-nm NIR laser on days 1 and 7. The temperature of HuH-7
      xenografts increased to 48.5  degrees C 3 minutes after ICG-NIR irradiation
      start. Reactive oxygen species (ROS) production was detected after ICG-NIR
      irradiation both in vitro and in vivo. There was certain anti-tumor effect and
      ROS production even under cooling conditions. Repeated NIR irradiation increased
      the cell toxicity of ICG-NIR therapy; the mean tumor volume on day 9 was
      significantly smaller after ICG-NIR irradiation compared to tumor without
      irradiation (87 mm3 vs. 1332 mm3; p = 0.01) in HCC mice xenografts model. ICG-NIR
      therapy induced apoptosis in HCC cells via a photothermal effect and oxidative
      stress. Repeated ICG-NIR irradiation enhanced the anti-tumor effect.

PMID- 29066755
TI  - Genomic variation in microbial populations inhabiting the marine subseafloor at
      deep-sea hydrothermal vents.
AB  - Little is known about evolutionary drivers of microbial populations in the warm
      subseafloor of deep-sea hydrothermal vents. Here we reconstruct 73 metagenome
      assembled genomes (MAGs) from two geochemically distinct vent fields in the Mid
      Cayman Rise to investigate patterns of genomic variation within subseafloor
      populations. Low-abundance populations with high intra-population diversity
      coexist alongside high-abundance populations with low genomic diversity, with
      taxonomic differences in patterns of genomic variation between the mafic Piccard
      and ultramafic Von Damm vent fields. Populations from Piccard are significantly
      enriched in nonsynonymous mutations, suggesting stronger purifying selection in
      Von Damm relative to Piccard. Comparison of nine Sulfurovum MAGs reveals two high
      coverage, low-diversity MAGs from Piccard enriched in unique genes related to the
      cellular membrane, suggesting these populations were subject to distinct
      evolutionary pressures that may correlate with genes related to nutrient uptake,
      biofilm formation, or viral invasion. These results are consistent with distinct
      evolutionary histories between geochemically different vent fields, with
      implications for understanding evolutionary processes in subseafloor microbial
      populations.

PMID- 29066757
TI  - Impaired K+ binding to glial glutamate transporter EAAT1 in migraine.
AB  - SLC1A3 encodes the glial glutamate transporter hEAAT1, which removes glutamate
      from the synaptic cleft via stoichiometrically coupled Na+-K+-H+-glutamate
      transport. In a young man with migraine with aura including hemiplegia, we
      identified a novel SLC1A3 mutation that predicts the substitution of a conserved
      threonine by proline at position 387 (T387P) in hEAAT1. To evaluate the
      functional effects of the novel variant, we expressed the wildtype or mutant
      hEAAT1 in mammalian cells and performed whole-cell patch clamp, fast substrate
      application, and biochemical analyses. T387P diminishes hEAAT1 glutamate uptake
      rates and reduces the number of hEAAT1 in the surface membrane. Whereas hEAAT1
      anion currents display normal ligand and voltage dependence in cells internally
      dialyzed with Na+-based solution, no anion currents were observed with internal
      K+. Fast substrate application demonstrated that T387P abolishes K+-bound
      retranslocation. Our finding expands the phenotypic spectrum of genetic variation
      in SLC1A3 and highlights impaired K+ binding to hEAAT1 as a novel mechanism of
      glutamate transport dysfunction in human disease.

PMID- 29066758
TI  - Genomic predictive model for recurrence and metastasis development in head and
      neck squamous cell carcinoma patients.
AB  - The head and neck squamous cell carcinoma (HNSCC) population consists mainly of
      high-risk for recurrence and locally advanced stage patients. Increased knowledge
      of the HNSCC genomic profile can improve early diagnosis and treatment outcomes.
      The development of models to identify consistent genomic patterns that
      distinguish HNSCC patients that will recur and/or develop metastasis after
      treatment is of utmost importance to decrease mortality and improve survival
      rates. In this study, we used array comparative genomic hybridization data from
      HNSCC patients to implement a robust model to predict HNSCC
      recurrence/metastasis. This predictive model showed a good accuracy (>80%) and
      was validated in an independent population from TCGA data portal. This predictive
      genomic model comprises chromosomal regions from 5p, 6p, 8p, 9p, 11q, 12q, 15q
      and 17p, where several upstream and downstream members of signaling pathways that
      lead to an increase in cell proliferation and invasion are mapped. The
      introduction of genomic predictive models in clinical practice might contribute
      to a more individualized clinical management of the HNSCC patients, reducing
      recurrences and improving patients' quality of life. The power of this genomic
      model to predict the recurrence and metastases development should be evaluated in
      other HNSCC populations.

PMID- 29066760
TI  - Simulating Moral Actions: An Investigation of Personal Force in Virtual Moral
      Dilemmas.
AB  - Advances in Virtual Reality (VR) technologies allow the investigation of
      simulated moral actions in visually immersive environments. Using a robotic
      manipulandum and an interactive sculpture, we now also incorporate realistic
      haptic feedback into virtual moral simulations. In two experiments, we found that
      participants responded with greater utilitarian actions in virtual and haptic
      environments when compared to traditional questionnaire assessments of moral
      judgments. In experiment one, when incorporating a robotic manipulandum, we found
      that the physical power of simulated utilitarian responses (calculated as the
      product of force and speed) was predicted by individual levels of psychopathy. In
      experiment two, which integrated an interactive and life-like sculpture of a
      human into a VR simulation, greater utilitarian actions continued to be observed.
      Together, these results support a disparity between simulated moral action and
      moral judgment. Overall this research combines state-of-the-art virtual reality,
      robotic movement simulations, and realistic human sculptures, to enhance moral
      paradigms that are often contextually impoverished. As such, this combination
      provides a better assessment of simulated moral action, and illustrates the
      embodied nature of morally-relevant actions.

PMID- 29066759
TI  - Fine-tuning of auxin homeostasis governs the transition from floral stem cell
      maintenance to gynoecium formation.
AB  - To ensure successful plant reproduction and crop production, the spatial and
      temporal control of the termination of the floral meristem must be coordinated.
      In Arabidopsis, the timing of this termination is determined by AGAMOUS (AG).
      Following its termination, the floral meristem underdoes gynoecium formation. A
      direct target of AG, CRABS CLAW (CRC), is involved in both floral meristem
      determinacy and gynoecium development. However, how floral meristem termination
      is coordinated with gynoecium formation is not understood. Here, we identify a
      mechanistic link between floral meristem termination and gynoecium development
      through fine-tuning of auxin homeostasis by CRC. CRC controls auxin homeostasis
      in the medial region of the developing gynoecium to generate proper auxin maxima.
      This regulation partially occurs via direct transcriptional repression of
      TORNADO2 (TRN2) by CRC. Plasma membrane-localized TRN2 modulates auxin
      homeostasis. We propose a model describing how regulation of auxin homeostasis
      mediates the transition from floral meristem termination to gynoecium
      development.

PMID- 29066761
TI  - RNase 7 participates in cutaneous innate control of Corynebacterium amycolatum.
AB  - Nondiphtheria corynebacteria are typical members of the skin microbiota. However,
      in addition to being harmless inhabitants of healthy skin commensal skin-derived
      corynebacteria such as C. amycolatum occasionally also cause infections. This
      suggests that human skin must harbor adequate mechanisms to control the growth of
      corynebacteria on the skin surface. Here we show that keratinocytes are able to
      detect the presence of C. amycolatum leading to the epidermal growth factor
      receptor (EGFR)-dependent induction of the antimicrobial protein RNase 7. C.
      amycolatum-mediated induction of RNase 7 was also confirmed in a human 3D skin
      equivalent. The functional relevance of these findings was demonstrated by potent
      antimicrobial activity of RNase 7 against C. amycolatum and C. xerosis. In
      addition, the capacity of human stratum corneum to restrict the growth of C.
      amycolatum was significantly attenuated when RNase 7 was inactivated by a
      specific RNase 7-neutralizing antibody. Taken together, the interaction of RNase
      7 with C. amycolatum indicates that RNase 7 may function as important effector
      molecule to control the growth of corynebacteria on human skin.

PMID- 29066762
TI  - Spatial constraints govern competition of mutant clones in human epidermis.
AB  - Deep sequencing can detect somatic DNA mutations in tissues permitting inference
      of clonal relationships. This has been applied to human epidermis, where sun
      exposure leads to the accumulation of mutations and an increased risk of skin
      cancer. However, previous studies have yielded conflicting conclusions about the
      relative importance of positive selection and neutral drift in clonal evolution.
      Here, we sequenced larger areas of skin than previously, focusing on cancer-prone
      skin spanning five decades of life. The mutant clones identified were too large
      to be accounted for solely by neutral drift. Rather, using mathematical modelling
      and computational lattice-based simulations, we show that observed clone size
      distributions can be explained by a combination of neutral drift and stochastic
      nucleation of mutations at the boundary of expanding mutant clones that have a
      competitive advantage. These findings demonstrate that spatial context and cell
      competition cooperate to determine the fate of a mutant stem cell.

PMID- 29066763
TI  - Urotensin II Exerts Pressor Effects By Stimulating Renin And Aldosterone Synthase
      Gene Expression.
AB  - We investigated the in vivo pressor effects of the potent vasoconstrictor
      Urotensin II (UII). We randomized normotensive Sprague-Dawley rats into 4 groups
      that received a 7-day UII infusion (cases) or vehicle (controls). Group 1
      received normal sodium intake; Group 2 underwent unilateral nephrectomy and salt
      loading; Group 3 received spironolactone, besides unilateral nephrectomy and salt
      loading; Group 4 only received spironolactone. UII raised BP transiently after a
      lag phase of 12-36 hours in Group 1, and progressively over the week in Group 2.
      Spironolactone did not affect blood pressure, but abolished both pressor effects
      of UII in Group 3, and left blood pressure unaffected in Group 4. UII increased
      by 7-fold the renal expression of renin in Group 2, increased aldosterone
      synthase expression in the adrenocortical zona glomerulosa, and prevented the
      blunting of renin expression induced by high salt. UII raises BP transiently when
      sodium intake and renal function are normal, but progressively in salt-loaded
      uninephrectomized rats. Moreover, it increases aldosterone synthase and
      counteracts the suppression of renin induced by salt loading. This novel action
      of UII in the regulation of renin and aldosterone synthesis could play a role in
      several clinical conditions where UII levels are up-regulated.

PMID- 29066764
TI  - Aberrant glioblastoma neovascularization patterns and their correlation with DCE
      MRI-derived parameters following temozolomide and bevacizumab treatment.
AB  - Glioblastoma (GBM) is a highly angiogenic malignancy, and its abundant, aberrant
      neovascularization is closely related to the proliferation and invasion of tumor
      cells. However, anti-angiogenesis combined with standard radio-/chemo-therapy
      produces little improvement in treatment outcomes. Determining the reason for
      treatment failure is pivotal for GBM treatment. Here, histopathological analysis
      and dynamic contrast-enhanced MRI (DCE-MRI) were used to explore the effects of
      temozolomide (TMZ) and bevacizumab (BEV) on GBM neovascularization patterns in an
      orthotopic U87MG mouse model at 1, 3 and 6 days after treatment. We found that
      the amount of vascular mimicry (VM) significantly increased 6 days after BEV
      treatment. TMZ inhibited neovascularization at an early stage, but the
      microvessel density (MVD) and transfer coefficient (Ktrans) derived from DCE-MRI
      increased 6 days after treatment. TMZ and BEV combination therapy slightly
      prolonged the inhibitory effect on tumor microvessels. Sprouting angiogenesis was
      positively correlated with Ktrans in all treatment groups. The increase in VM
      after BEV administration and the increase in MVD and Ktrans after TMZ
      administration may be responsible for treatment resistance. Ktrans holds great
      potential as an imaging biomarker for indicating the variation in sprouting
      angiogenesis during drug treatment for GBM.

PMID- 29066765
TI  - Computational reconstruction reveals a candidate magnetic biocompass to be likely
      irrelevant for magnetoreception.
AB  - Birds use the magnetic field of the Earth to navigate during their annual
      migratory travel. The possible mechanism to explain the biophysics of this
      compass sense involves electron transfers within the photoreceptive protein
      cryptochrome. The magnetoreceptive functioning of cryptochromes is supposedly
      facilitated through an iron rich polymer complex which couples to multiple
      cryptochromes. The present investigation aims to independently reconstruct this
      complex and describe its interaction with Drosophila melanogaster cryptochromes.
      The polymer complex consists of ISCA1 protein monomers with internally bound iron
      sulphur clusters and simultaneously binds ten cryptochromes. Through molecular
      dynamics we have analysed the stability of the ISCA1-cryptochrome complex and
      characterized the interaction at the binding sites between individual
      cryptochrome and ISCA1. It is found that the cryptochrome binding to the ISCA1
      polymer is not uniform and that the binding affinity depends on its placement
      along the ISCA1 polymer. This finding supports the claim that the individual
      ISCA1 monomer acts as possible intracellular interaction partner of cryptochrome,
      but the proposed existence of an elongated ISCA1 polymer with multiple attached
      cryptochromes appears to be questionable.

PMID- 29066766
TI  - Live Cell Imaging Reveals pH Oscillations in Saccharomyces cerevisiae During
      Metabolic Transitions.
AB  - Addition of glucose to starved Saccharomyces cerevisiae initiates collective NADH
      dynamics termed glycolytic oscillations. Numerous questions remain about the
      extent to which single cells can oscillate, if oscillations occur in natural
      conditions, and potential physiological consequences of oscillations. In this
      paper, we report sustained glycolytic oscillations in single cells without the
      need for cyanide. Glucose addition to immobilized cells induced pH oscillations
      that could be imaged with fluorescent sensors. A population of cells had
      oscillations that were heterogeneous in frequency, start time, stop time,
      duration and amplitude. These changes in cytoplasmic pH were necessary and
      sufficient to drive changes in NADH. Oscillators had lower mitochondrial membrane
      potentials and budded more slowly than non-oscillators. We also uncovered a new
      type of oscillation during recovery from H2O2 challenge. Our data show that pH in
      S. cerevisiae changes over several time scales, and that imaging pH offers a new
      way to measure glycolytic oscillations on individual cells.

PMID- 29066767
TI  - Incidence and Risk Factors of in-hospital mortality from AKI after non
      cardiovascular operation: A nationwide Survey in China.
AB  - This study aimed to describe the mortality and risk factors of in-hospital
      mortality from acute kidney injury (AKI) after non-cardiovascular operation in
      China based on a nationwide survey about AKI. The study sample was drawn from ISN
      AKF 0by25 China Consortiums, which is a nationwide, cross-sectional survey from
      22 provinces in mainland China. AKI after non-cardiovascular operation was
      identified according to the 2012 KDIGO AKI creatinine criteria or expanded
      criteria. In total, 3468 cases were identified as hospital-acquired AKI (HA-AKI).
      Of these, 1059 cases were defined as AKI after major non-cardiovascular surgery.
      Post-operative AKI and non-operative AKI were similar in aetiology and in the
      need for RRT intervention. The all-cause in-hospital mortality was 17.0% (180 of
      1059) among patients with AKI after a major surgery. Older age (OR = 1.14, p =
      0.046), more severe comorbidities (OR = 9.29, p < 0.001), a history of CVD (OR =
      1.85, p = 0.007), more severe peak AKI stage, and being located in the northwest
      region of China (OR = 2.47, p = 0.012) were all significantly associated with
      increased in-hospital mortality risk in AKI patients who underwent an operation.
      AKI after a non-cardiovascular operation has become a huge medical burden in
      China. The features of operative AKI varied substantially in different regions of
      China. Increased attention must be paid to the occurrence of potential intrinsic
      renal AKI when patients are exposed to nephrotoxic factors or comorbidities.

PMID- 29066768
TI  - Functional classification of protein toxins as a basis for bioinformatic
      screening.
AB  - Proteins are fundamental to life and exhibit a wide diversity of activities, some
      of which are toxic. Therefore, assessing whether a specific protein is safe for
      consumption in foods and feeds is critical. Simple BLAST searches may reveal
      homology to a known toxin, when in fact the protein may pose no real danger.
      Another challenge to answer this question is the lack of curated databases with a
      representative set of experimentally validated toxins. Here we have
      systematically analyzed over 10,000 manually curated toxin sequences using
      sequence clustering, network analysis, and protein domain classification. We also
      developed a functional sequence signature method to distinguish toxic from non
      toxic proteins. The current database, combined with motif analysis, can be used
      by researchers and regulators in a hazard screening capacity to assess the
      potential of a protein to be toxic at early stages of development. Identifying
      key signatures of toxicity can also aid in redesigning proteins, so as to
      maintain their desirable functions while reducing the risk of potential health
      hazards.

PMID- 29066769
TI  - Dynamically controllable plasmon induced transparency based on hybrid metal
      graphene metamaterials.
AB  - Novel hybrid metal-graphene metamaterials featuring dynamically controllable
      single, double and multiple plasmon induced transparency (PIT) windows are
      numerically explored in the terahertz (THz) regime. The designed plasmonic
      metamaterials composed of a strip and a ring with graphene integration generate a
      novel PIT window. Once the ring is divided into pairs of asymmetrical arcs,
      double PIT windows both with the spectral contrast ratio 100% are obtained, where
      one originates from the destructive interference between bright-dark modes, and
      the other is based on the interaction of bright-bright modes. Just because the
      double PIT windows are induced by two different mechanisms, the continuously
      controllable conductivity and damping of graphene are employed to appropriately
      interpret the high tunability in double transparency peaks at the resonant
      frequency, respectively. Moreover, multiple PIT windows can be achieved by
      introducing an additional bright mode to form the other bright-bright modes
      coupling. At the PIT transparent windows, the dispersions undergo tremendous
      modifications and the group delays reach up to 43 ps, 22 ps, and 25 ps,
      correspondingly. Our results suggest the existence of strong interaction between
      the monolayer graphene layer and metal-based resonant plasmonic metamaterials,
      which may hold widely applications in filters, modulators, switching, sensors and
      optical buffers.

PMID- 29066770
TI  - Measurement of Crystalline Silica Aerosol Using Quantum Cascade Laser-Based
      Infrared Spectroscopy.
AB  - Inhalation exposure to airborne respirable crystalline silica (RCS) poses major
      health risks in many industrial environments. There is a need for new sensitive
      instruments and methods for in-field or near real-time measurement of crystalline
      silica aerosol. The objective of this study was to develop an approach, using
      quantum cascade laser (QCL)-based infrared spectroscopy (IR), to quantify
      airborne concentrations of RCS. Three sampling methods were investigated for
      their potential for effective coupling with QCL-based transmittance measurements:
      (i) conventional aerosol filter collection, (ii) focused spot sample collection
      directly from the aerosol phase, and (iii) dried spot obtained from deposition of
      liquid suspensions. Spectral analysis methods were developed to obtain IR spectra
      from the collected particulate samples in the range 750-1030 cm-1. The new
      instrument was calibrated and the results were compared with standardized methods
      based on Fourier transform infrared (FTIR) spectrometry. Results show that
      significantly lower detection limits for RCS (~330 ng), compared to conventional
      infrared methods, could be achieved with effective microconcentration and careful
      coupling of the particulate sample with the QCL beam. These results offer promise
      for further development of sensitive filter-based laboratory methods and portable
      sensors for near real-time measurement of crystalline silica aerosol.

PMID- 29066771
TI  - Therapeutic potential of the phosphino Cu(I) complex (HydroCuP) in the treatment
      of solid tumors.
AB  - [Cu(thp)4][PF6] (HydroCuP) is a phosphino copper(I) complex highly soluble and
      stable in physiological media that has been developed as a possible viable
      alternative to platinum-based drugs for anticancer therapy. HydroCuP potently
      inhibited the growth of human cancer cells derived from solid tumors by inducing
      endoplasmatic reticulum (ER) stress thus leading to cell death through paraptosis
      with a preferential efficacy against cancer rather than non-cancer cells. Aim of
      the present study was to assess the therapeutic potential of HydroCuP in vivo, in
      syngenic and xenograft murine models of solid tumors by triggering the Unfolded
      Protein Response (UPR) pathway. With respect to platinum drugs, HydroCuP induced
      a markedly higher reduction of tumor growth associated with minimal animal
      toxicity. In human colorectal cancer xenografts, chemotherapy with HydroCuP was
      extremely effective in both oxaliplatin-sensitive and resistant models. The
      favorable in vivo tolerability of HydroCuP was also correlated to an encouraging
      biodistribution profile. Additionally, no signs of drug-related neurotoxicity and
      nephrotoxicity were observed. Altogether, these results demonstrate that HydroCuP
      appears worth of further investigation to evaluate its therapeutic activity
      towards a broad spectrum of solid malignancies.

PMID- 29066773
TI  - Biomechanical Simulation of Stress Concentration and Intraocular Pressure in
      Corneas Subjected to Myopic Refractive Surgical Procedures.
AB  - Recent advances in the analysis of corneal biomechanical properties remain
      difficult to predict the structural stability before and after refractive
      surgery. In this regard, we applied the finite element method (FEM) to determine
      the roles of the Bowman's membrane, stroma, and Descemet's membrane in the hoop
      stresses of cornea, under tension (physiological) and bending (nonphysiological),
      for patients who undergo radial keratotomy (RK), photorefractive keratectomy
      (PRK), laser-assisted in situ keratomileusis (LASIK), or small incision lenticule
      extraction (SMILE). The stress concentration maps, potential creak zones, and
      potential errors in intraocular pressure (IOP) measurements were further
      determined. Our results confirmed that the Bowman's membrane and Descemet's
      membrane accounted for 20% of the bending rigidity of the cornea, and became the
      force pair dominating the bending behaviour of the cornea, the high stress in the
      distribution map, and a stretch to avoid structural failure. In addition, PRK
      broke the central linking of hoop stresses and concentrated stress on the edge of
      the Bowman's membrane around ablation, which posed considerable risk of potential
      creaks. Compared with SMILE, LASIK had a higher risk of developing creaks around
      the ablation in the stroma layer. Our FEM models also predicted the postoperative
      IOPs precisely in a conditional manner.

PMID- 29066774
TI  - Role of the luxS gene in bacteriocin biosynthesis by Lactobacillus plantarum
      KLDS1.0391: A proteomic analysis.
AB  - Certain probiotic species of lactic acid bacteria, especially Lactobacillus
      plantarum, regulate bacteriocin synthesis through quorum sensing (QS) systems. In
      this study, we aimed to investigate the luxS-mediated molecular mechanisms of QS
      during bacteriocin synthesis by L. plantarum KLDS1.0391. In the absence of luxS,
      the 'spot-on-the-lawn' method showed that the bacteriocin production by L.
      plantarum KLDS1.0391 significantly decreased upon co-cultivation with L.
      helveticus KLDS1.9207 (P < 0.01) but did not change significantly when mono
      cultivated. Furthermore, liquid chromatography-electrospray ionization tandem
      mass spectrometry analysis showed that, as a response to luxS deletion, L.
      plantarum KLDS1.0391 altered the expression level of proteins involved in
      carbohydrate metabolism, amino acid metabolism, fatty acid synthesis and
      metabolism, and the two-component regulatory system. In particular, the sensor
      histidine kinase AgrC (from the two-component system, LytTR family) was expressed
      differently between the luxS mutant and the wild-type strain during co
      cultivation, whereas no significant differences in proteins related to
      bacteriocin biosynthesis were found upon mono-cultivation. In summary, we found
      that the production of bacteriocin was regulated by carbohydrate metabolism,
      amino acid metabolism, fatty acid synthesis and metabolism, and the two-component
      regulatory system. Furthermore, our results demonstrate the role of luxS-mediated
      molecular mechanisms in bacteriocin production.

PMID- 29066772
TI  - Transcription factor TFEB cell-autonomously modulates susceptibility to
      intestinal epithelial cell injury in vivo.
AB  - Understanding the transcription factors that modulate epithelial resistance to
      injury is necessary for understanding intestinal homeostasis and injury repair
      processes. Recently, transcription factor EB (TFEB) was implicated in expression
      of autophagy and host defense genes in nematodes and mammalian cells. However,
      the in vivo roles of TFEB in the mammalian intestinal epithelium were not known.
      Here, we used mice with a conditional deletion of Tfeb in the intestinal
      epithelium (Tfeb DeltaIEC) to examine its importance in defense against injury.
      Unperturbed Tfeb DeltaIEC mice exhibited grossly normal intestinal epithelia,
      except for a defect in Paneth cell granules. Tfeb DeltaIEC mice exhibited lower
      levels of lipoprotein ApoA1 expression, which is downregulated in Crohn's disease
      patients and causally linked to colitis susceptibility. Upon environmental
      epithelial injury using dextran sodium sulfate (DSS), Tfeb DeltaIEC mice
      exhibited exaggerated colitis. Thus, our study reveals that TFEB is critical for
      resistance to intestinal epithelial cell injury, potentially mediated by APOA1.

PMID- 29066775
TI  - Quantum coherence of the Heisenberg spin models with Dzyaloshinsky-Moriya
      interactions.
AB  - We study quantum coherence in a spin chain with both symmetric exchange and
      antisymmetric Dzyaloshinsky-Moriya couplings. Quantum coherence is quantified
      using the recently introduced quantum Jensen-Shannon divergence, which has the
      property that it is easily calculable and has several desirable mathematical
      properties. We calculate exactly the coherence for arbitrary number of spins at
      zero temperature in various limiting cases. The sigma z sigma z interaction tunes
      the amount of coherence in the system, and the antisymmetric coupling changes the
      nature of the coherence. We also investigate the effect of non-zero temperature
      by looking at a two-spin system and find similar behavior, with temperature
      dampening the coherence. The characteristic behavior of coherence resembles that
      of entanglement and is opposite to that of discord. The distribution of the
      coherence on the spins is investigated and found that it arises entirely due to
      the correlations between the spins.

PMID- 29066776
TI  - Highlighting the crucial role of Hangzhou in HIV-1 transmission among men who
      have sex with men in Zhejiang, China.
AB  - In recent years, the population of men who have sex with men (MSM) constitute a
      major group for HIV transmission in China. A total of 340 newly reported HIV
      infected MSM were recruited proportionally from ten prefectures across Zhejiang
      province between January and December in 2013. Partial pol gene was amplified and
      sequenced. Phylogenetic relationship, transmission network and genotypic drug
      resistance analyses were performed on 311 sequences. HIV-1 subtypes including
      CRF01_AE (55.9%), CRF07_BC (37.6%), subtype B (1.9%), CRF55_01B (1.3%), CRF68_01B
      (0.3%), CRF08_BC (0.3%) and URFs (2.6%) were identified. A higher proportion of
      CRF07_BC and other subtypes existed in the >35 years group, while a higher
      proportion of CRF01_AE was present in the young group (<35 years). Low prevalence
      of transmitted drug resistance was found (3.9%, 12/311). Strains with Hangzhou
      imprints were diffused across the full phylogenetic tree. Moreover, Hangzhou
      represented the dominant proportion of local HIV transmission (72.0%) and cross
      regional transmission (62.4%) based on the provincial transmission network and
      possessed the largest number of nodes with >=50 edges, accounting for 50.0%
      (10/20). The complexity of HIV subtypes and an intertwined network was noticed in
      MSM in Zhejiang province. Hangzhou likely plays a central regional role in the
      intra-provincial spread of HIV.

PMID- 29066777
TI  - Poverty eradication in a carbon constrained world.
AB  - The UN Framework Convention on Climate Change aims to keep warming below 2 
      degrees C while recognizing developing countries' right to eradicate extreme
      poverty. Poverty eradication is also the first of the Sustainable Development
      Goals. This paper investigates potential consequences for climate targets of
      achieving poverty eradication. We find that eradicating extreme poverty, i.e.,
      moving people to an income above $1.9 purchasing power parity (PPP) a day, does
      not jeopardize the climate target even in the absence of climate policies and
      with current technologies. On the other hand, bringing everybody to a still
      modest expenditure level of at least $2.97 PPP would have long-term consequences
      on achieving emission targets. Compared to the reference mitigation pathway,
      eradicating extreme poverty increases the effort by 2.8% whereas bringing
      everybody to at least $2.97 PPP would increase the required mitigation rate by
      27%. Given that the top 10% global income earners are responsible for 36% of the
      current carbon footprint of households; the discourse should address income
      distribution and the carbon intensity of lifestyles.

PMID- 29066778
TI  - Structural, physicochemical and dynamic features conserved within the aerolysin
      pore-forming toxin family.
AB  - Aerolysin is the founding member of a major class of beta-pore-forming toxins
      (beta-PFTs) found throughout all kingdoms of life. PFTs are cytotoxic proteins
      produced as soluble monomers, which oligomerize at the membrane of target host
      cells forming pores that may lead to osmotic lysis and cell death. Besides their
      role in microbial infection, they have become interesting for their potential as
      biotechnological sensors and delivery systems. Using an approach that integrates
      bioinformatics with molecular modeling and simulation, we looked for conserved
      features across this large toxin family. The cell surface-binding domains present
      high variability within the family to provide membrane receptor specificity. On
      the contrary, the novel concentric double beta-barrel structure found in
      aerolysin is highly conserved in terms of sequence, structure and conformational
      dynamics, which likely contribute to preserve a common transition mechanism from
      the prepore to the mature pore within the family.Our results point to the key
      role of several amino acids in the conformational changes needed for
      oligomerization and further pore formation, such as Y221, W227, P248, Q263 and
      L277, which we propose are involved in the release of the stem loop and the two
      adjacent beta-strands to form the transmembrane beta-barrel.

PMID- 29066779
TI  - Effect of population, collection year, after-ripening and incubation condition on
      seed germination of Stipa bungeana.
AB  - Knowledge of the germination behavior of different populations of a species can
      be useful in the selection of appropriate seed sources for restoration. The aim
      of this study was to test the effect of seed population, collection year, after
      ripening and incubation conditions on seed dormancy and germination of Stipa
      bungeana, a perennial grass used for revegetation of degraded grasslands on the
      Loess Plateau, China. Fresh S. bungeana seeds were collected from eight locally
      adapted populations in 2015 and 2016. Dormancy and germination characteristics of
      fresh and 6-month-old dry-stored seeds were determined by incubating them over a
      range of alternating temperature regimes in light. Effect of water stress on
      germination was tested for fresh and 6-month-old dry-stored seeds. Seed dormancy
      and germination of S. bungeana differed with population and collection year. Six
      months of dry storage broke seed dormancy, broadened the temperature range for
      germination and increased among-population differences in germination percentage.
      The rank order of germination was not consistent in all germination tests, and it
      varied among populations. Thus, studies on comparing seed dormancy and
      germination among populations must consider year of collection, seed dormancy
      states and germination test conditions when selecting seeds for grassland
      restoration and management.

PMID- 29066780
TI  - Survival Motor Neuron Protein is Released from Cells in Exosomes: A Potential
      Biomarker for Spinal Muscular Atrophy.
AB  - Spinal muscular atrophy (SMA) is caused by homozygous mutation of the survival
      motor neuron 1 (SMN1) gene. Disease severity inversely correlates to the amount
      of SMN protein produced from the homologous SMN2 gene. We show that SMN protein
      is naturally released in exosomes from all cell types examined. Fibroblasts from
      patients or a mouse model of SMA released exosomes containing reduced levels of
      SMN protein relative to normal controls. Cells overexpressing SMN protein
      released exosomes with dramatically elevated levels of SMN protein. We observed
      enhanced quantities of exosomes in the medium from SMN-depleted cells, and in
      serum from a mouse model of SMA and a patient with Type 3 SMA, suggesting that
      SMN-depletion causes a deregulation of exosome release or uptake. The quantity of
      SMN protein contained in the serum-derived exosomes correlated with the genotype
      of the animal, with progressively less protein in carrier and affected animals
      compared to wildtype mice. SMN protein was easily detectable in exosomes isolated
      from human serum, with a reduction in the amount of SMN protein in exosomes from
      a patient with Type 3 SMA compared to a normal control. Our results suggest that
      exosome-derived SMN protein may serve as an effective biomarker for SMA.

PMID- 29066781
TI  - Global hotspots and correlates of emerging zoonotic diseases.
AB  - Zoonoses originating from wildlife represent a significant threat to global
      health, security and economic growth, and combatting their emergence is a public
      health priority. However, our understanding of the mechanisms underlying their
      emergence remains rudimentary. Here we update a global database of emerging
      infectious disease (EID) events, create a novel measure of reporting effort, and
      fit boosted regression tree models to analyze the demographic, environmental and
      biological correlates of their occurrence. After accounting for reporting effort,
      we show that zoonotic EID risk is elevated in forested tropical regions
      experiencing land-use changes and where wildlife biodiversity (mammal species
      richness) is high. We present a new global hotspot map of spatial variation in
      our zoonotic EID risk index, and partial dependence plots illustrating
      relationships between events and predictors. Our results may help to improve
      surveillance and long-term EID monitoring programs, and design field experiments
      to test underlying mechanisms of zoonotic disease emergence.

PMID- 29066782
TI  - Altered physiochemical properties in industrially synthesized ZnO nanoparticles
      regulate oxidative stress; induce in vivo cytotoxicity in embryonic zebrafish by
      apoptosis.
AB  - This study investigates the in vivo cytotoxicity of ZnO nanoparticles synthesized
      at industrial scale with embryonic Zebrafish. Industrial synthesis of ZnO
      nanoparticles was mimicked at lab scale by high energy ball milling technique by
      milling bulk ZnO particles for 15 h. Synthesized 7 h and 10 h ZnO nanoparticles
      showed significant alteration of size, zeta potential and optical properties in
      comparison to Bulk ZnO. Mortality and hatching rate in Zebrafish embryos were
      influenced by these alterations. Size and charge dependent effect of ZnO
      nanoparticles exposure on physiology and development of Zebrafish embryos were
      evident by malfunctioned organ development and abnormal heartbeat rate. Similar
      dependency on quenching of ROS due to influential hydrogen bond interaction with
      glycine residue of Sod1 oxidative stress protein and increased apoptosis were
      observed in cells. The study revealed the mechanism of cytotoxicity in exposed
      embryonic Zebrafish as an effect of accumulation and internalization inside cells
      instigating to generation of hypoxic condition and interference with the normal
      adaptive stress regulation signaling pathways leading towards enhanced apoptosis.
      The study revealed hidden size and charge dependent in vivo cytotoxicity
      mechanism of ZnO nanoparticles in Zebrafish embryos insight of the environmental
      and clinical importance of attention on industrially synthesized ZnO
      nanoparticles.

PMID- 29066784
TI  - Density-dependence in the declining population of the monarch butterfly.
AB  - The Eastern monarch butterfly population has significantly declined over the last
      two decades creating growing concerns around its conservation status. Here, we
      showed that the overwintering population exhibited a negative density-dependence
      (i.e. a negative effect on growth rate of the density in the previous year) and
      that, after accounting for the density effect, the population growth rate tended
      to decline over time. The negative time effect is probably linked to the host
      plant (i.e. milkweed) decline in North America. A negative density-dependence was
      also found in the time series of both egg density per host plant and adult
      density across North America suggesting the importance of a bottom-up, resource
      driven regulation such as host plant limitation and/or of a top-down regulation
      through generalist natural enemies or diseases. The temporal stability of the
      density effect indicated that the negative density-dependence and the population
      decline are likely independent phenomena. One of the most common conclusions of
      previous research is that environmental stochasticity is the dominant key
      compounded driver of population dynamics. We showed that density dependence
      explained 37-50% of the total variation in growth rate in three independent
      datasets, indicating that several non-exclusive density-related mechanisms can be
      important in monarch population dynamics.

PMID- 29066783
TI  - Canine dorsal root ganglia satellite glial cells represent an exceptional cell
      population with astrocytic and oligodendrocytic properties.
AB  - Dogs can be used as a translational animal model to close the gap between basic
      discoveries in rodents and clinical trials in humans. The present study compared
      the species-specific properties of satellite glial cells (SGCs) of canine and
      murine dorsal root ganglia (DRG) in situ and in vitro using light microscopy,
      electron microscopy, and immunostainings. The in situ expression of CNPase, GFAP,
      and glutamine synthetase (GS) has also been investigated in simian SGCs. In situ,
      most canine SGCs (>80%) expressed the neural progenitor cell markers nestin and
      Sox2. CNPase and GFAP were found in most canine and simian but not murine SGCs.
      GS was detected in 94% of simian and 71% of murine SGCs, whereas only 44% of
      canine SGCs expressed GS. In vitro, most canine (>84%) and murine (>96%) SGCs
      expressed CNPase, whereas GFAP expression was differentially affected by culture
      conditions and varied between 10% and 40%. However, GFAP expression was induced
      by bone morphogenetic protein 4 in SGCs of both species. Interestingly, canine
      SGCs also stimulated neurite formation of DRG neurons. These findings indicate
      that SGCs represent an exceptional, intermediate glial cell population with
      phenotypical characteristics of oligodendrocytes and astrocytes and might possess
      intrinsic regenerative capabilities in vivo.

PMID- 29066786
TI  - Rapid on-site evaluation of the development of resistance to quinone outside
      inhibitors in Botrytis cinerea.
AB  - Botrytis cinerea, a typical "high-risk" pathogenic fungus that rapidly develops
      resistance to fungicides, affects more than 1,000 species of 586 plant genera
      native to most continents and causes great economic losses. Therefore, a rapid
      and sensitive assay of fungicide resistance development in B. cinerea populations
      is crucial for scientific management. In this study, we established a Loop
      mediated isothermal amplification (LAMP) system for the monitoring and evaluation
      of the risk of development of B. cinerea resistance to QoI fungicides; the method
      uses two LAMP assays. The first assay detects G143A mutants of B. cinerea, which
      are highly resistance to QoI fungicides. BCbi143/144 introns in B. cinerea are
      then detected by the second assay. HNB acts as a visual LAMP reaction indicator.
      The optimum reaction conditions of the LAMP assays were 61  degrees C for 50 min,
      and the detection limit of the LAMP assays was 100 * 10-4 ng/MUl. We directly pre
      treated the field samples by using All-DNA-Fast-Out to extract DNA within ten
      minutes, then performed the LAMP assay to achieve one-step rapid detection. In
      conclusion, we established a rapid and sensitive LAMP assay system for resistance
      risk assessment and for monitoring QoI-resistance of B. cinerea in the field.

PMID- 29066785
TI  - Silicon Photonics Transmitter with SOA and Semiconductor Mode-Locked Laser.
AB  - We experimentally investigate an optical link relying on silicon photonics
      transmitter and receiver components as well as a single section semiconductor
      mode-locked laser as a light source and a semiconductor optical amplifier for
      signal amplification. A transmitter based on a silicon photonics resonant ring
      modulator, an external single section mode-locked laser and an external
      semiconductor optical amplifier operated together with a standard receiver
      reliably supports 14 Gbps on-off keying signaling with a signal quality factor
      better than 7 for 8 consecutive comb lines, as well as 25 Gbps signaling with a
      signal quality factor better than 7 for one isolated comb line, both without
      forward error correction. Resonant ring modulators and Germanium waveguide
      photodetectors are further hybridly integrated with chip scale driver and
      receiver electronics, and their co-operability tested. These experiments will
      serve as the basis for assessing the feasibility of a silicon photonics
      wavelength division multiplexed link relying on a single section mode-locked
      laser as a multi-carrier light source.

PMID- 29066787
TI  - Nitrogen recycling at the Costa Rican subduction zone: The role of incoming plate
      structure.
AB  - Efficient recycling of subducted sedimentary nitrogen (N) back to the atmosphere
      through arc volcanism has been advocated for the Central America margin while at
      other locations mass balance considerations and N contents of high pressure
      metamorphic rocks imply massive addition of subducted N to the mantle and past
      the zones of arc magma generation. Here, we report new results of N isotope
      compositions with gas chemistry and noble gas compositions of forearc and arc
      front springs in Costa Rica to show that the structure of the incoming plate has
      a profound effect on the extent of N subduction into the mantle. N isotope
      compositions of emitted arc gases (9-11 N degrees ) imply less subducted pelagic
      sediment contribution compared to farther north. The N isotope compositions
      (delta15N = -4.4 to 1.60/00) of forearc springs at 9-11 N degrees  are consistent
      with previously reported values in volcanic centers (delta15N = -3.0 to 1.90/00).
      We advocate that subduction erosion enhanced by abundant seamount subduction at 9
      11 N degrees  introduces overlying forearc crustal materials into the Costa Rican
      subduction zone, releasing fluids with lighter N isotope signatures. This process
      supports the recycling of heavier N into the deep mantle in this section of the
      Central America margin.

PMID- 29066788
TI  - Periodontal pathogenic bacteria, Aggregatibacter actinomycetemcomitans affect non
      alcoholic fatty liver disease by altering gut microbiota and glucose metabolism.
AB  - Increasing evidence indicates that periodontitis affects non-alcoholic fatty
      liver disease (NAFLD). We examined the relationship between periodontal bacterial
      infection and clinical/biochemical parameters in 52 NAFLD patients. Anti
      Aggregatibacter actinomycetemcomitans (Aa) antibody titers correlated positively
      with visceral fat, fasting plasma insulin, and HOMA-IR; and negatively with the
      liver/spleen ratio. C57BL/6J mice (8-weeks-old) were given Aa or saline (control)
      for 6 weeks, and were fed either normal chow (NCAa, NCco) or high-fat diet (HFAa
      and HFco). NCAa and HFAa mice presented impaired glucose tolerance and insulin
      resistance compared to control mice. HFAa mice showed higher hepatic steatosis
      than HFco animals. Liver microarray analysis revealed that 266 genes were
      differentially expressed between NCAa and NCco mice. Upregulated genes in Aa
      administrated mice were enriched for glucagon signaling pathway, adipocytokine
      signaling pathway and insulin resistance. Consistently, plasma glucagon
      concentration was higher in NCAa mice. In addition, Akt phosphorylation was lower
      in the liver of NCAa/HFAa than in NCco/HFco mice. Based on 16S rRNA sequencing,
      Aa administration changed composition of the gut microbiota. Metagenome
      prediction in gut microbiota showed upregulation of fatty acid biosynthesis and
      downregulation of fatty acid degradation in Aa-administered mice. Thus, infection
      with Aa affects NAFLD by altering the gut microbiota and glucose metabolism.

PMID- 29066789
TI  - Identification of 14-dehydroergosterol as a novel anti-inflammatory compound
      inducing tolerogenic dendritic cells.
AB  - Tolerogenic dendritic cells (DCs) have the ability to induce regulatory T cells
      and play an important role in preventing chronic inflammatory and autoimmune
      diseases. We have identified a novel compound, 14-dehydroergosterol, from Koji, a
      Japanese traditional food material fermented with fungi. 14-dehydroergosterol is
      an ergosterol analogue with a conjugated double bond, but the activity of 14
      dehydroergosterol is much higher than that of ergosterol. 14-dehydroergosterol
      induces the conversion of murine bone marrow (BM)-derived DCs and differentiated
      DCs into tolerogenic DCs, in which the production of IL-12 is suppressed and that
      of IL-10 is increased. In a co-culture experiment, DCs treated with 14
      dehydroergosterol induced the conversion of naive CD4-positive T cells into
      regulatory T cells. In a murine model of multiple sclerosis, experimental
      autoimmune encephalopathy, 14-dehydroergosterol suppressed the clinical score and
      inflammatory responses of myeloid DCs and T cells to myelin oligodendrocyte
      glycoprotein. 14-dehydroergosterol-treated human DCs induced from PBMCs also
      showed a tolerogenic phenotype. This is the first report to identify a novel
      compound, 14-dehydroergosterol, that induces DCs to convert to a tolerogenic
      type. 14-dehydroergosterol is contained in various fermented foods based on Koji,
      so 14-dehydroergosterol might be a helpful aid to prevent chronic inflammatory
      and autoimmune diseases.

PMID- 29066790
TI  - Challenges and discoveries in the total synthesis of complex polyketide natural
      products.
AB  - Structurally complex polyketide natural products, isolated from a variety of
      marine and terrestrial sources, continue to provide a valuable source of
      rewarding targets for the synthetic chemist to tackle. In this account, we
      provide an overview of the total synthesis of several structurally fascinating
      polyketides with promising anticancer activity completed in our group based on
      our versatile asymmetric aldol methodology-spirastrellolide A methyl ester,
      leiodermatolide, rhizopodin and chivosazole F-and highlight the unanticipated
      challenges and discoveries encountered.

PMID- 29066791
TI  - Amycolatopsins A-C: antimycobacterial glycosylated polyketide macrolides from the
      Australian soil Amycolatopsis sp. MST-108494.
AB  - A southern Australian soil isolate, Amycolatopsis sp. MST-108494, was subjected
      to a panel of fermentation and media optimization trials, supported by analytical
      chemical profiling, to detect and enhance production of a rare class of secondary
      metabolites. Chemical fractionation of two complementary fermentations yielded
      three new polyketides, identified by detailed spectroscopic analysis as the
      glycosylated macrolactones, amycolatopsins A (1), B (2) and C (3), closely
      related to the ammocidins and apoptolidins. Amycolatopsins 1 and 3 selectively
      inhibited growth of Mycobacterium bovis (BCG) and Mycobacterium tuberculosis
      (H37Rv) when compared with other Gram-positive or Gram-negative bacteria, with 3
      exhibiting low levels of cytotoxicity toward mammalian cells. Thus, our data
      reveal promising structure activity relationship correlations where the
      antimycobacterial properties of amycolatopsins are enhanced by hydroxylation of
      the 6-Me (that is, 1 and 3), whereas mammalian cytotoxicity is decreased by
      hydrolysis of the disaccharide moiety (that is, 3).

PMID- 29066793
TI  - Phenazine carboxylic acid and its derivative induce osteoblast differentiation in
      preosteoblastic MC3T3-E1 cells but adipocyte differentiation in pluripotent
      mesenchymal C3H10T1/2 cells.
AB  - Osteoblast and adipocyte are differentiated from mesenchymal stem cells and
      dysregulation of the differentiation might result in disease, such as
      osteoporosis and diabetes. To find small compounds that induce osteoblast
      differentiation, we screened an in-house natural compounds library with mouse
      preosteoblastic MC3T3-E1 cells using alkaline phosphatase (ALP) expression as an
      early osteoblast marker. We found that phenazine-1-carboxylic acid (PCA), one of
      the major phenazine derivatives produced by Pseudomonas, induced osteoblast
      differentiation in the cells at micromolar concentrations. PCA acted
      synergistically with an agonist of hedgehog signaling in inducing ALP activity in
      the cells. We also found that 2-hydroxy-PCA (2H-PCA) induced osteoblast
      differentiation in the cells but 2-methoxy-PCA and 1-hydroxy-phenazine did not.
      Unexpectedly, treatment of mouse pluripotent mesenchymal C3H10T1/2 cells with PCA
      or 2H-PCA induced an obvious morphological change. Oil Red O staining and real
      time reverse-transcription PCR analysis revealed that PCA induced not osteoblast
      differentiation but adipocyte differentiation in C3H10T1/2 cells. These compounds
      could allow us to investigate the mechanism of osteoblast and adipocyte
      differentiation in the two model cell systems through a chemical biology
      approach.

PMID- 29066794
TI  - Enantiospecific total synthesis of the squalene synthase inhibitors (-)-CJ-13,982
      and its enantiomer from a common intermediate.
AB  - The total syntheses of both the natural and unnatural enantiomers of the alkyl
      citrate natural product CJ-13,982 (1) from the common d-ribose-derived acid 6 are
      described.

PMID- 29066792
TI  - Lanostane triterpenoids from fruiting bodies of basidiomycete Stereum sp.,
      structures and biological activities.
AB  - Twelve new lanostane triterpenoids, sterenoids A-L (1-12) have been isolated from
      fruiting bodies of the basidiomycete Stereum sp. Compounds 1-12 are rare 14(13
      >?12)abeo-lanostane triterpenoids featuring remarkable 13R configurations that
      discriminate from the previously covered counterparts. Their structures and
      absolute configurations are assigned on the basis of in-depth one- and two
      dimensional NMR spectroscopic analysis, as well as unbiased quantum chemical NMR
      and electronic CD calculations. All isolates are evaluated for their in vitro
      cytotoxicity against five human tumor cell lines. Compound 5 exhibits potent
      cytotoxic activities against tumor cell lines HL-60 and SMMC-7721 with IC50
      values of 4.7 and 7.6 MUM, respectively.

PMID- 29066795
TI  - A new eremophilane sesquiterpene from the fungus Xylaria sp. V-27 and inhibition
      activity against degranulation in RBL-2H3 cells.
AB  - A new eremophilane sesquiterpene, 13,13-dimethoxyintegric acid (1), together with
      known compound integric acid (2) have been isolated from a fungus, Xylaria sp. V
      27, obtained from a dead branch. The structure of 1 was established by means of
      spectroscopic analyses. 1 and 2 promoted growth restoring activity against the
      mutant yeast strain (Saccharomyces cerevisiae (zds1Delta erg3Delta pdr1Delta
      pdr3Delta)) and inhibited degranulation of rat basophilic leukemia RBL-2H3 cells
      stimulated by immnunoglobulin G + 2,4-dinitrophenylated-bovine serum albumin
      (IgE+DNP-BSA), thapsigargin and A23187.

PMID- 29066796
TI  - New eremophilane and dichlororesorcinol derivatives produced by endophytes
      isolated from Ficus ampelas.
AB  - The novel compound, 11-O-methylpetasitol (1), was isolated from Penicillium sp. N
      175-1, and two new compounds, cosmochlorins D (5) and E (6), were isolated from
      Phomopsis sp. N-125. In addition, three known eremophilane sesquiterpenes,
      sporogen-AO1 (2), petasol (3) and 6-dehydropetasol (4), were isolated from
      Penicillium sp. N-175-1. The structures of 1, 5 and 6 were elucidated by a
      combination of extensive spectroscopic analyses, including 2D NMR, high
      resolution electrospray ionization time-of-flight mass spectrometry (HRESITOFMS)
      and chemical reactions. Compounds 2, 3, 5 and 6 exhibited cytotoxicity to HL60
      and 2 and 3 to HeLa cells. Furthermore, 2 and 3 showed robust growth-restoring
      activity of a Saccharomyces cerevisiae (cdc2-1 rad9Delta) mutant strain, whereas
      5 and 6 exhibited minor growth-restoring activity in this strain. Thus, these
      compounds may inhibit the growth of HL60 and HeLa cells by blocking the cell
      cycle, and they may be utilized as new lead compounds that act as inhibitors of
      survival signal transduction pathways.

PMID- 29066798
TI  - Embracing diversity gives antibodies the power to bind.

PMID- 29066799
TI  - Unusual isothermal multimerization and amplification by the strand-displacing DNA
      polymerases with reverse transcription activities.
AB  - ABSTARCT: Existing isothermal nucleic acid amplification (INAA) relying on the
      strand displacement activity of DNA polymerase usually requires at least two
      primers. However, in this paper, we report an unusual isothermal multimerization
      and amplification (UIMA) which only needs one primer and is efficiently initiated
      by the strand-displacing DNA polymerases with reverse transcription activities.
      On electrophoresis, the products of UIMA present a cascade-shape band and they
      are confirmed to be multimeric DNAs with repeated target sequences. In contrast
      to current methods, UIMA is simple to product multimeric DNA, due to the
      independent of multiple primers and rolling circle structures. Through assaying
      the synthesized single-stranded DNA targets, UIMA performs high sensitivity and
      specificity, as well as the universality. In addition, a plausible mechanism of
      UIMA is proposed, involving short DNA bending, mismatch extension, and template
      slippage. UIMA is a good explanation for why nonspecific amplification easily
      happens in existing INAAs. As the simplest INAA till now, UIMA provides a new
      insight for deeply understanding INAA and opens a new avenue for thoroughly
      addressing nonspecific amplification.

PMID- 29066800
TI  - Wave Manipulations by Coherent Perfect Channeling.
AB  - We show that through the wave energy conserved and reversible process of coherent
      interactions of scalar waves in a multi-channel system joint by a common
      junction, it is possible to generate outgoing waves only in certain channels by
      controlling the incoming waves. We refer to such processes as coherent perfect
      channeling (CPC). As two particular examples, we report experimental and
      theoretical investigations of CPC with two incoming coherent waves in three and
      four-channel waveguides that are completely channeled into one or two other
      waveguides mediated by a deep subwavelength dimension scatterer at the common
      junction. Two such scatterers are discovered, one confirmed by experiments and
      the other predicted by theory, and their scattering matrices are constructed.
      Scatterers with other CPC scattering matrices are explored, and preliminary
      investigations of their properties are conducted. The scattering matrix formulism
      makes it possible to extend the domain of CPC to other scalar waves, such as
      electromagnetic waves and quantum wavefunctions.

PMID- 29066797
TI  - Destination of aminoglycoside antibiotics in the 'post-antibiotic era'.
AB  - Aminoglycoside antibiotics (AGAs) were developed at the dawn of the antibiotics
      era and have significantly aided in the treatment of infectious diseases.
      Aminoglycosides have become one of the four major types of antibiotics in use
      today and, fortunately, still have an important role in the clinical treatment of
      severe bacterial infections. In this review, the current usage, modes of action
      and side effects of AGAs, along with the most common bacterial resistance
      mechanisms, are outlined. Finally, the recent development situation and
      possibility of new AGAs in the 'post-antibiotic era' are considered.The Journal
      of Antibiotics advance online publication, 25 October 2017;
      doi:10.1038/ja.2017.117.

PMID- 29066801
TI  - Investigation of causes of sex-related differences in ocular blood flow in
      healthy eyes determined by laser speckle flowgraphy.
AB  - Sex-related differences are present in the systemic and ocular blood flow.
      However, the cause of the sex-related differences has not been determined. We
      investigated the ocular blood flow, represented by the mean blur rate (MBR), on
      the optic nerve head (ONH) determined by laser speckle flowgraphy in 138 males
      (63.9 +/- 8.9 years) and 194 females (63.5 +/- 9.4 years). The correlations
      between the MBR on the ONH and the clinical data were determined. The overall ONH
      MBR was significantly higher in females than males (P < 0.001). In addition, the
      levels of the hemoglobin and hematocrit were significantly lower in females than
      in males (P < 0.001). The ONH-MBR was negatively and significantly correlated
      with the levels of the hemoglobin and hematocrit (both, P < 0.001). Multiple
      regression analyses showed that the sex (beta = 0.248, P < 0.001) was an
      independent factor correlated with the ONH-MBR when the clinical examination data
      were not included in the analyses. However, when the clinical examination data
      were included, the hemoglobin level (beta = -0.295, P < 0.001) was an independent
      factor that contributed to the ONH-MBR but the sex was not. We conclude that the
      sex-related differences in the hemoglobin level and the negative correlation
      between hemoglobin and the ONH-MBR are the causes of the sex-related differences
      in the ONH-MBR.

PMID- 29066802
TI  - Molecular Cloning of the Vitellogenin Gene and the Effects of Vitellogenin
      Protein Expression on the Physiology of Harmonia axyridis (Coleoptera:
      Coccinellidae).
AB  - Vitellogenin (Vg), the main egg storage protein precursor, plays an integral role
      in many oviparous animals, including Harmonia axyridis, an important agent for
      the biological control of many insect pests. In this study, the full-length Vg
      gene of was cloned. The open reading frame (ORF) of H. axyridis Vg cDNA is 5,403
      bp in length and encodes 1,800 amino acids, with a predicted molecular mass of
      211.88 KDa (accession number in NCBI: KX442718). Recombinant protein (18 kDa)
      expressed by the cloned Vg gene was characterized, and the effects of the
      expression of this protein on the physiology of H. axyridis were investigated. We
      found that Vg fragment significantly increased the egg production of H. axyridis.
      Furthermore, we also found that the activities of trypsin and lipase in H.
      axyridis were significantly higher in the groups treated with Vg fragment
      compared with those of the controls. The data from this study also reveals that
      Vg expression has significant effects on the physiology of H. axyridis and leads
      to increased egg production in these insects. These results may have future
      implications for increasing the reproduction rates of beneficial insects.

PMID- 29066803
TI  - Bat songs as acoustic beacons - male territorial songs attract dispersing
      females.
AB  - Male song in birds and mammals is important for repelling rivals, stimulating
      mates or attracting them to a specific location. Nevertheless, direct
      experimental evidence for the mate attraction function of male song is limited to
      a few studies. Here, we provide strong experimental evidence that male songs
      attract wild female bats (Saccopteryx bilineata). Playbacks of territorial songs
      reliably elicited phonotaxis in females but not males. Most females captured
      during playbacks were subadults searching for new colonies to settle in. In S.
      bilineata, multiple males sing simultaneously at dawn and dusk, thereby creating
      a conspicuous chorus which encodes information on colony identity and size. Since
      territorial songs have a large signalling range, male songs constitute acoustic
      beacons which enable females to localize new colonies. In our playbacks, females
      strongly preferred local territorial songs over foreign territorial songs from
      two different locations, indicating that song familiarity influences phonotaxis.
      Our study provides the first clear experimental evidence that male song elicits
      female phonotaxis in a non-human mammal. Bats are an especially promising taxon
      for studying mammalian song since male song has been described in different
      species with diverse social organisations and natural histories, thus providing
      exciting opportunities for phylogenetically controlled comparative studies.

PMID- 29066804
TI  - On the relevance of the alpha frequency oscillation's small-world network
      architecture for cognitive flexibility.
AB  - Cognitive flexibility is a major requirement for successful behavior. nNeural
      oscillations in the alpha frequency band were repeatedly associated with
      cognitive flexibility in task-switching paradigms. Alpha frequencies are
      modulated by working memory load and are used to process information during task
      switching, however we do not know how this oscillatory network communication is
      modulated. In order to understand the mechanisms that drive cognitive
      flexibility, ERPs, oscillatory power and how the communication within these
      networks is organized are of importance. The EEG data show that during phases
      reflecting preparatory processes to pre-activate task sets, alpha oscillatory
      power but not the small world properties of the alpha network architecture was
      modulated. During the switching only the N2 ERP component showed clear
      modulations. After the response, alpha oscillatory power reinstates and therefore
      seems to be important to deactivate or maintain the previous task set. For these
      reactive control processes the network architecture in terms of small-world
      properties is modulated. Effects of memory load on small-world aspects were seen
      in repetition trials, where small-world properties were higher when memory
      processes were relevant. These results suggest that the alpha oscillatory network
      becomes more small-world-like when reactive control processes during task
      switching are less complex.

PMID- 29066805
TI  - Uptake of glucose-conjugated MGMT inhibitors in cancer cells: role of flippases
      and type IV P-type ATPases.
AB  - The DNA repair protein O 6-methylguanine-DNA-methyltransferase (MGMT) is a key
      determinant of cancer resistance. The MGMT inhibitors O 6-benzylguanine (O6BG)
      and O 6-(4-bromothenyl)guanine (O6BTG) failed to enhance the therapeutic response
      due to toxic side effects when applied in combination with alkylating
      chemotherapeutics, indicating a need of inhibitor targeting. We assessed MGMT
      targeting that relies on conjugating the inhibitors O6BG and O6BTG to beta-D
      glucose, resulting in O6BG-Glu and O6BTG-Glu, respectively. This targeting
      strategy was selected by taking advantage of high demand of glucose in cancers.
      Contrary to our expectation, the uptake of O6BG-Glu and O6BTG-Glu was not
      dependent on glucose transporters. Instead, it seems that after membrane binding
      the conjugates are taken up via flippases, which normally transport
      phospholipids. This membrane binding is the consequence of the amphiphilic
      character of the conjugates, which at higher concentrations lead to the formation
      of micelle-like particles in aqueous solution. The unusual uptake mechanism of
      the conjugates highlights the importance of proper linker selection for a
      successful ligand-based drug delivery strategy. We also demonstrate that proteins
      of the P4-Type ATPase family are involved in the transport of the glucose
      conjugates. The findings are not only important for MGMT inhibitor targeting, but
      also for other amphiphilic drugs.

PMID- 29066807
TI  - Effects of Recovery Time during Magnetic Nanofluid Hyperthermia on the Induction
      Behavior and Efficiency of Heat Shock Proteins 72.
AB  - In this study, we investigated the effects of recovery time during magnetic
      nanofluid hyperthermia (MNFH) on the cell death rate and the heat shock proteins
      72 (HSP72) induction behavior in retinal ganglion cells (RGCs-5) to provide a
      possible solution for highly efficient ocular neuroprotection. The recovery time
      and the heat duration time during MNFH were systematically controlled by changing
      the duty cycle of alternating current (AC) magnetic field during MNFH. It was
      clearly observed that the cell death rate and the HSP72 induction rate had a
      strong dependence on the recovery time and the optimizated recovery time resulted
      in maximizing the induction efficiency of HSP72. Controlling the recovery time
      during MNFH affects not only the cell death rate but also HSP72 induction rate.
      The cell death rate after MNFH was dramatically decreased by increasing the
      recovery time during MNFH. However, it was also found that the HSP72 induction
      rate was slightly decreased by increasing the recovery time. These results
      indicate that applying the appropriate or optimized recovery time during MNFH can
      improve the induction efficiency of HSP72 by minimizing the cell death caused by
      cytotoxic effects of heat.

PMID- 29066806
TI  - Phosphoinositide-specific phospholipase Cgamma1 inhibition induces autophagy in
      human colon cancer and hepatocellular carcinoma cells.
AB  - Phosphoinositide-specific phospholipase C (PLC) gamma1 has been reported to be
      involved in cancer cell proliferation and metastasis. However, whether PLCgamma1
      modulates autophagy and the underlying mechanism remains unclear. Here, we
      investigated the relationship between PLCgamma1 and autophagy in the human colon
      cancer cell line HCT116 and hepatocellular carcinoma cell line HepG2. The results
      indicated that PLCgamma1 inhibition via lentivirus-mediated transduction with
      shRNA/PLCgamma1 or transient transfection with pRK5-PLCgamma1 (Y783A) vector
      increased LC3B-II levels and the number of autophagic vacuoles and decreased p62
      levels. Addition of an autophagy inhibitor led to LC3B and p62 accumulation.
      Furthermore, AMPK activation promoted the autophagy induced by PLCgamma1
      inhibition by blocking the FAK/PLCgamma1 axis. In addition, PLCgamma1 inhibition
      either blocked the mTOR/ULK1 axis or enhanced dissociation of the Beclin1-IP3R
      Bcl-2 complex to induce autophagy. Taken together, our findings revealed that
      PLCgamma1 inhibition induced autophagy and the FAK/PLCgamma1 axis is a potential
      downstream effector of the AMPK activation-dependent autophagy signalling
      cascade. Both blockade of the mTOR/ULK1 axis and dissociation of the Beclin1-IP3R
      Bcl-2 complex contributed to the induction of autophagy by PLCgamma1 inhibition.
      Consequently, these findings provide novel insight into autophagy regulation by
      PLCgamma1 in colon cancer and hepatocellular carcinoma cells.

PMID- 29066808
TI  - Cross-tissue integration of genetic and epigenetic data offers insight into
      autism spectrum disorder.
AB  - Integration of emerging epigenetic information with autism spectrum disorder
      (ASD) genetic results may elucidate functional insights not possible via either
      type of information in isolation. Here we use the genotype and DNA methylation
      (DNAm) data from cord blood and peripheral blood to identify SNPs associated with
      DNA methylation (meQTL lists). Additionally, we use publicly available fetal
      brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue
      specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P <
      0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD
      meQTLs across cord, blood, and brain tissues are enriched for immune-related
      pathways, consistent with other expression and DNAm results in ASD, and reveal
      pathways not implicated by genetic findings. This joint analysis of genotype and
      DNAm demonstrates the potential of both brain and blood-based DNAm for insights
      into ASD and psychiatric phenotypes more broadly.

PMID- 29066809
TI  - Obstetric outcomes in pregnant women with and without depression: population
      based comparison.
AB  - This study used insurance claims data to evaluate obstetric outcomes in pregnant
      women with and without depression because population study for Asian women on the
      issue is limited. We identified 5,064 women with depression at pregnancy in 2005
      2013, and 20,024 pregnant women without depression, frequency matched by age,
      pregnant year and parity. Obstetric events during pregnancy and deliveries were
      evaluated. The depression group had more events than comparisons for hyperemesis
      (39.3 vs. 35.5%), abortion (3.3 vs. 2.6%), malpresentation (12.3 vs. 10.3%), C
      section (40.2 vs. 34.6%) and intrauterine fetal demise (0.7 vs. 0.4%); risks of
      these events were significant for childbearing depressed women, not for the 35+
      years subgroup. These incidences were higher in depressed women taking
      antidepressant than those without the medication, but were significant in
      childbearing depressed subgroup for hyperemesis and C-section with odds ratios of
      1.18 (95% confidence intervals (CI), 1.02-1.36) and 1.29 (95% CI, 1.11-1.49),
      respectively. Incident preterm and low birth weight births were also higher in
      the depression group than in comparisons, but weren't significant. In conclusion,
      women with depression during pregnancy may develop more adverse events than
      comparisons and are more likely to have a C-section delivery.

PMID- 29066811
TI  - Biodiversity research requires more boots on the ground.

PMID- 29066810
TI  - Immunotherapy with subcutaneous immunogenic autologous tumor lysate increases
      murine glioblastoma survival.
AB  - Immunotherapeutic strategies for glioblastoma, the most frequent malignant
      primary brain tumor, aim to improve its disastrous consequences. On top of the
      standard treatment, one strategy uses T cell activation by autologous dendritic
      cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells.
      Wondering whether 'targeting' in vivo DCs could replace these ex vivo ones,
      immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in
      the absence of ex vivo loaded DCs. Potential immune mechanisms were studied in
      two orthotopic, immunocompetent murine glioma models. Pre-tumoral subcutaneous
      lysate treatment resulted in a survival benefit comparable to subcutaneous DC
      therapy. Focussing on the immune response, glioma T cell infiltration was
      observed in parallel with decreased amounts of regulatory T cells. Moreover,
      these results were accompanied by the presence of strong tumor-specific
      immunological memory, shown by complete survival of a second glioblastoma tumor,
      inoculated 100 days after the first one. Finally, in combination with
      temozolomide, survival of established glioma in mice could be increased. Our
      results show the potential of immunogenic autologous tumor lysate used to treat
      murine glioblastoma, which will be worthwhile to study in clinical trials as it
      has potential as a cost-efficient adjuvant treatment strategy for gliomas.

PMID- 29066812
TI  - The importance of cancer cells for animal evolutionary ecology.

PMID- 29066814
TI  - More than half the Earth.

PMID- 29066813
TI  - Planetary boundaries for a blue planet.
AB  - Concepts underpinning the planetary boundaries framework are being incorporated
      into multilateral discussions on sustainability, influencing international
      environmental policy development. Research underlying the boundaries has
      primarily focused on terrestrial systems, despite the fundamental role of marine
      biomes for Earth system function and societal wellbeing, seriously hindering the
      efficacy of the boundary approach. We explore boundaries from a marine
      perspective. For each boundary, we show how improved integration of marine
      systems influences our understanding of the risk of crossing these limits. Better
      integration of marine systems is essential if planetary boundaries are to inform
      Earth system governance.

PMID- 29066815
TI  - Rice cultivation in ancient Amazonia.

PMID- 29066817
TI  - Deficit irrigation and planting patterns strategies to improve maize yield and
      water productivity at different plant densities in semi-arid regions.
AB  - Field research was done in two consecutive years to optimize deficit irrigation
      under different crop densities (low, medium, and high) using the ridge and furrow
      rainfall harvesting (RFRH) system. We demonstrate that applying deficit
      irrigation (375 m3 ha-1) at the flowering stage of maize grown at medium density
      (M: 75000 plant ha-1) under the RFRH system (MIF) can improve soil water storage
      (0-200 cm) at the bell, filling and flowering stages. MIF increased biomass by
      10% and grain yield by 21%, thereby achieving a 17% increase in water use
      efficiency (WUE) and a 22% increase in precipitation use efficiency (PUE)
      compared with conventional flat planting (CKM). MIF also improved irrigation
      water use efficiency (IWUE) (9%) and irrigation water productivity (IWP) (46%)
      compared with no-irrigation under the RFRH system (MI0). We observed that
      applying deficit irrigation (750 m3 ha-1) at the bell and flowering stage (IBF)
      had positive effects on dry matter, leaf area, and evapotranspiration, but there
      were no significant increases in IWUE, IWP, WUE, biomass and grain yield compared
      with maize grown under IF at low, medium and high plant densities. The average
      net profit over the two years was 34% higher for MIF compared with the CKM
      treatment.

PMID- 29066816
TI  - Host factors that modify Plasmodium falciparum adhesion to endothelial receptors.
AB  - P. falciparum virulence is related to adhesion and sequestration of infected
      erythrocytes (IE) in deep vascular beds, but the endothelial receptors involved
      in severe malaria remain unclear. In the largest ever study of clinical isolates,
      we surveyed adhesion of freshly collected IE from children under 5 years of age
      in Mali to identify novel vascular receptors, and examined the effects of host
      age, hemoglobin type, blood group and severe malaria on levels of IE adhesion to
      a panel of endothelial receptors. Several novel molecules, including integrin
      alpha3beta1, VE-cadherin, ICAM-2, junctional adhesion molecule-B (JAM-B),
      laminin, and cellular fibronectin, supported binding of IE from children. Severe
      malaria was not significantly associated with levels of IE adhesion to any of the
      19 receptors. Hemoglobin AC, which reduces severe malaria risk, reduced IE
      binding to the receptors CD36 and integrin alpha5beta1, while hemoglobin AS did
      not modify IE adhesion to any receptors. Blood groups A, AB and B significantly
      reduced IE binding to ICAM-1. Severe malaria risk varies with age, but age
      significantly impacted the level of IE binding to only a few receptors: IE
      binding to JAM-B decreased with age, while binding to CD36 and integrin
      alpha5beta1 significantly increased with age.

PMID- 29066818
TI  - Seawater transfer alters the intestinal microbiota profiles of Atlantic salmon
      (Salmo salar L.).
AB  - Atlantic salmon undergo dramatic physiological changes as they migrate from
      freshwater to the marine environment. Osmoregulatory adaptation is the most
      crucial change, necessitating functional adaptations of the gills, kidney and
      intestine. Additionally, novel pathogens, microbes and dietary items are
      encountered in the saltwater environment, which suggests major changes in the
      intestinal microbiota following movement to saltwater. Here we compared the
      intestinal microbiota harboured in the distal digesta of Atlantic salmon
      freshwater fish (FW) kept in a commercial Scottish freshwater hatchery with that
      of their full-siblings after seawater acclimatisation (SW) by a 16S rRNA (V3-V4)
      high-throughput sequencing approach. Alpha- and beta-diversity were found
      significantly higher in FW compared to SW, both in terms of richness and
      diversity. Metastats analysis identified a higher number of Operational Taxonomic
      Units (OTUs) unique to FW compared to SW, with an additional 238 OTUs found at
      significantly different abundance. A core microbiota of 19 OTUs was identified in
      100% of all fish, which indicates that certain microbes are maintained to fulfil
      minimal functions within the gut. Furthermore we show that the uniqueness of the
      respective microbial profiles can be correlated with significant differences in
      KEGG pathways including lipid and amino acid metabolism.

PMID- 29066819
TI  - Immunotherapy: Gain beyond injection.

PMID- 29066821
TI  - Large-scale DNA Barcode Library Generation for Biomolecule Identification in High
      throughput Screens.
AB  - High-throughput screens allow for the identification of specific biomolecules
      with characteristics of interest. In barcoded screens, DNA barcodes are linked to
      target biomolecules in a manner allowing for the target molecules making up a
      library to be identified by sequencing the DNA barcodes using Next Generation
      Sequencing. To be useful in experimental settings, the DNA barcodes in a library
      must satisfy certain constraints related to GC content, homopolymer length,
      Hamming distance, and blacklisted subsequences. Here we report a novel framework
      to quickly generate large-scale libraries of DNA barcodes for use in high
      throughput screens. We show that our framework dramatically reduces the
      computation time required to generate large-scale DNA barcode libraries, compared
      with a naive approach to DNA barcode library generation. As a proof of concept,
      we demonstrate that our framework is able to generate a library consisting of one
      million DNA barcodes for use in a fragment antibody phage display screening
      experiment. We also report generating a general purpose one billion DNA barcode
      library, the largest such library yet reported in literature. Our results
      demonstrate the value of our novel large-scale DNA barcode library generation
      framework for use in high-throughput screening applications.

PMID- 29066823
TI  - Organoids: Modelling polycystic kidney disease.

PMID- 29066820
TI  - DNA N6-methyladenine is dynamically regulated in the mouse brain following
      environmental stress.
AB  - Chemical modifications on DNA molecules, such as 5-methylcytosine and 5
      hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA
      adenine modification, N(6)-methyladenine (6mA), has recently been found in
      mammalian cells. However, the presence and function(s) of 6mA in the mammalian
      brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in
      response to environmental stress. We find that overall 6mA levels are
      significantly elevated upon stress. Genome-wide 6mA and transcriptome profiling
      reveal an inverse association between 6mA dynamic changes and a set of
      upregulated neuronal genes or downregulated LINE transposon expression. Genes
      bearing stress-induced 6mA changes significantly overlap with loci associated
      with neuropsychiatric disorders. These results suggest an epigenetic role for 6mA
      in the mammalian brain as well as its potential involvement in neuropsychiatric
      disorders.

PMID- 29066824
TI  - Towards properties on demand in quantum materials.
AB  - The past decade has witnessed an explosion in the field of quantum materials,
      headlined by the predictions and discoveries of novel Landau-symmetry-broken
      phases in correlated electron systems, topological phases in systems with strong
      spin-orbit coupling, and ultra-manipulable materials platforms based on two
      dimensional van der Waals crystals. Discovering pathways to experimentally
      realize quantum phases of matter and exert control over their properties is a
      central goal of modern condensed-matter physics, which holds promise for a new
      generation of electronic/photonic devices with currently inaccessible and likely
      unimaginable functionalities. In this Review, we describe emerging strategies for
      selectively perturbing microscopic interaction parameters, which can be used to
      transform materials into a desired quantum state. Particular emphasis will be
      placed on recent successes to tailor electronic interaction parameters through
      the application of intense fields, impulsive electromagnetic stimulation, and
      nanostructuring or interface engineering. Together these approaches outline a
      potential roadmap to an era of quantum phenomena on demand.

PMID- 29066822
TI  - Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal
      (iN) cells from NF1 patients: a pilot study.
AB  - Direct conversion technique to produce induced-neuronal (iN) cells from human
      fibroblasts within 2 weeks is expected to discover unknown neuronal phenotypes of
      neuropsychiatric disorders. Here, we present unique gene expression profiles in
      iN cells from patients with neurofibromatosis type 1 (NF1), a single-gene
      multifaceted disorder with comparatively high co-occurrence of autism spectrum
      disorder (ASD). Microarray-based transcriptomic analysis on iN cells from male
      healthy controls and male NF1 patients (NF1-iN cells) revealed that 149 genes
      expressions were significantly different (110 upregulated and 39 downregulated).
      We validated that mRNA of MEX3D (mex-3 RNA binding family member D) was lower in
      NF1-iN cells by real-time PCR with 12 sex-mixed samples. In NF1-iN cells on day
      14, higher expression of FOS mRNA was observed with lower expression of MEX3D
      mRNA. Interestingly, BCL2 mRNA was higher in NF1-iN cells on day 5 (early-period)
      but not on day 14. Our data suggest that aberrant molecular signals due to NF1
      mutations may disturb gene expressions, a subset of which defines continuum of
      the neuronal phenotypes of NF1 with ASD. Further translational studies using
      induced pluripotent stem (iPS) cell-derived neuronal cells are needed to validate
      our preliminary findings especially confirming meanings of analysis using early
      period iN cells.

PMID- 29066825
TI  - Topological states of condensed matter.
AB  - Topological states of quantum matter have been investigated intensively in recent
      years in materials science and condensed matter physics. The field developed
      explosively largely because of the precise theoretical predictions, well
      controlled materials processing, and novel characterization techniques. In this
      Perspective, we review recent progress in topological insulators, the quantum
      anomalous Hall effect, chiral topological superconductors, helical topological
      superconductors and Weyl semimetals.

PMID- 29066826
TI  - Material witness: Get a grip.

PMID- 29066827
TI  - Stranger things.

PMID- 29066828
TI  - Quantum materials discovery from a synthesis perspective.
AB  - The synthesis of bulk crystals, thin films and nanostructures plays a seminal
      role in expanding the frontiers of quantum materials. Crystal growers accomplish
      this by creating materials aimed at harnessing the complex interplay between
      quantum wavefunctions and various factors such as dimensionality, topology,
      Coulomb interactions and symmetry. This Review provides a synthesis perspective
      on how this discovery of quantum materials takes place. After introducing the
      general paradigms that arise in this context, we provide a few examples to
      illustrate how thin-film growers in particular exploit quantum confinement,
      topology, disorder and interfacial heterogeneity to realize new quantum
      materials.

PMID- 29066829
TI  - Nanocrystalline metals: Roughness in flatland.

PMID- 29066830
TI  - Imaging quantum materials.

PMID- 29066831
TI  - Cell-free DNA: Treasure trove for cancer medicine.

PMID- 29066832
TI  - Unusual Electromagnetic Signatures of European North Atlantic Winter
      Thunderstorms.
AB  - All lightning strokes generate electromagnetic pulses -atmospherics- which can
      travel over distances of thousands of kilometers. Night-side atmospherics show
      typical frequency dispersion signatures caused by sub-ionospheric propagation.
      Their analysis can be used to determine the distance to the source lightning, and
      therefore it represents a safe tool for investigation of distant thunderstorms,
      as well as for indirect observations of the lower ionosphere. However, such
      analysis has never been done on the dayside. Here we present the first results
      which show unusual daytime atmospherics with dispersion signatures originating
      from strong thunderstorms which occurred during winter months 2015 in the North
      Atlantic region. Using newly developed analysis techniques for 3-component
      electromagnetic measurements we are able to determine the source azimuth and to
      attribute these rare atmospherics to both positive and negative lightning strokes
      in northern Europe. We consistently find unusually large heights of the
      reflective ionospheric layer which are probably linked to low fluxes of solar X
      rays and which make the dayside subionospheric propagation possible. Although the
      atmospherics are linearly polarized, their dispersed parts exhibit left handed
      polarization, consistent with the anticipated continuous escape of the right-hand
      polarized power to the outer space in the form of whistlers.

PMID- 29066833
TI  - Effects of the discharge of uranium mining effluents on the water quality of the
      reservoir: an integrative chemical and ecotoxicological assessment.
AB  - The water quality of the Antas reservoir, under the influence of treated
      effluents from a uranium mining area Ore Treatment Unit (UTM) with acid mine
      drainage, was investigated. Samples were collected every 3 months from the Antas
      reservoir (CAB, P41-E and P14) and from the UTM (P41-S). Chemical and acute 48 h
      toxicity tests using Ceriodaphnia silvestrii and Daphnia magna analyses were
      carried out to determine the potential environmental risks due to discharging the
      uranium mine effluents into this reservoir. All the water samples taken from the
      treated effluent (P41-S) were positively correlated with elevated concentrations
      of uranium, manganese, aluminum, zinc and fluoride and with high electrical
      conductivity and pH values, being considered toxic. In November 2014 water
      samples taken from the reservoir showed chemical concentrations above the
      legislation limits for fluoride (4.5 mg L-1) uranium (0.082 mg L-1), sulfate
      (662.4 mg L-1), manganese (1.125 mg L-1) and aluminum (1.55 mg L-1), and in July
      2015 for fluoride (2.55 mg L-1), uranium (0.01 mg L-1) and manganese (0.36 mg L
      1). The extremely high average value for hardness (543.55 mg L-1) possibly
      reduced the toxicity potential of this chemical species mixture with respect to
      the bioindicators. The influence of the variation in water hardness on the
      toxicity of the cladocerans was discussed.

PMID- 29066834
TI  - Definitive Radiotherapy for Older Patients with Prostate Cancer: Experience of a
      Medical Center in Taiwan.
AB  - Whether age predicts treatment outcome of prostate cancer remains controversial.
      With the aging of the world population, properly understanding the effect of age
      may facilitate both treatment decision-making and defining the natural history of
      prostate cancer. Consecutive 581 patients with locally-confined adenocarcinoma of
      the prostate who received radical definitive radiotherapy(RT) (76-78 Gy) between
      2004 and 2015 at a medical center in Taiwan were reviewed retrospectively. Median
      age was 78 years. The median follow-up was 66 months. The 5-year biochemical
      failure-free survival(BFFS), distant metastasis-free survival(DMFS), disease
      specific survival(DSS), and overall survival(OS) rates were 84.9%, 93.8%, 97.8%,
      and 86.6%, respectively, for all patients. Comparing those above and below the
      age of 80, no difference in 5-year BFFS, DMFS, or DSS was found. Multivariate Cox
      regression analysis showed that tumor stage, Gleason score, initial PSA, and
      latency before RT were significant risk factors of BFFS. The latency before RT
      was significantly longer in the older group than in the under 80 group. Delay to
      start RT might explain the previous finding of inferior disease control in older
      patients in other studies. With the exception of OS, no other differences in
      outcomes or toxicities were observed in older patients.

PMID- 29066835
TI  - Cellular hormetic response to 27-hydroxycholesterol promotes neuroprotection
      through AICD induction of MAST4 abundance and kinase activity.
AB  - The function of the amyloid precursor protein (APP) in brain health remains
      unclear. This study elucidated a novel cytoprotective signaling pathway initiated
      by the APP transcriptionally active intracellular domain (AICD) in response to 27
      hydroxycholesterol (27OHC), an oxidized cholesterol metabolite associated with
      neurodegeneration. The cellular response to 27OHC was hormetic, such that low,
      but not high, doses promoted AICD transactivation of microtubule associated
      serine/threonine kinase family member 4 (MAST4). MAST4 in turn phosphorylated and
      inhibited FOXO1-dependent transcriptional repression of rhotekin 2 (RTKN2), an
      oxysterol stress responder, to optimize cell survival. A palmitate-rich diet,
      which increases serum 27OHC, or APP ablation, abrogated this response in vivo.
      Further, this pathway was downregulated in human Alzheimer's Disease (AD) brains
      but not in frontotemporal dementia brains. These results unveil MAST4 as
      functional kinase of FOXO1 in a 27OHC AICD-driven, hormetic pathway providing
      insight for therapeutic approaches against cholesterol associated neuronal
      disorders.

PMID- 29066836
TI  - A platform for efficient identification of molecular phenotypes of brain-wide
      neural circuits.
AB  - A neural circuit is a structural-functional unit of achieving particular
      information transmission and processing, and have various inputs, outputs and
      molecular phenotypes. Systematic acquisition and comparative analysis of the
      molecular features of neural circuits are crucial to elucidating the operating
      mechanisms of brain function. However, no efficient, systematic approach is
      available for describing the molecular phenotypes of specific neural circuits at
      the whole brain scale. In this study, we developed a rapid whole-brain optical
      tomography method and devised an efficient approach to map brain-wide structural
      and molecular information in the same brain: rapidly imaging and sectioning the
      whole brain as well as automatically collecting all slices; conveniently
      selecting slices of interest through quick data browsing and then performing post
      hoc immunostaining of selected slices. Using this platform, we mapped the brain
      wide distribution of inputs to motor, sensory and visual cortices and determined
      their molecular phenotypes in several subcortical regions. Our platform
      significantly enhances the efficiency of molecular phenotyping of neural circuits
      and provides access to automation and industrialization of cell type analyses for
      specific circuits.

PMID- 29066837
TI  - A strategy to improve arithmetical performance in four day-old domestic chicks
      (Gallus gallus).
AB  - A large body of literature shows that non-human animals master numerical
      discriminations, but a limit has been reported in a variety of species in the
      comparison 3vs.4. Little is known regarding the possibility of using "cognitive
      strategies" to enable this discrimination. The aims of this study were to
      investigate: whether domestic chicks discriminated 3vs.4, and if changes in
      stimuli presentation could improve chicks' numerical performance. Newly hatched
      chicks were reared with seven identical objects. On day 4, they underwent 20
      consecutive testing trials to assess their capability to discriminate 3vs.4. The
      objects were presented, one-by-one, to the chicks and hidden behind one of two
      identical panels. As expected, the chicks did not discriminate (Experiment 1).
      When objects were presented and hidden in groups comprising one or two objects (2
      + 1)vs.(2 + 2), the chicks succeeded (Experiment 2). The grouping strategy did
      not help in the case of a harder discrimination of (3 + 1)vs.(3 + 2) (Experiment
      3), unless chicks were allowed to rest for two hours between testing sessions
      (Experiment 4). Our results suggest that in some cases, the limits reported for
      numerical performance in animals do not depend on cognitive limitations but on
      attentional or motivational factors, which can be overcome employing simple
      procedural adjustments.

PMID- 29066838
TI  - Optimization Strategies for Bruch's Membrane Opening Minimum Rim Area
      Calculation: Sequential versus Simultaneous Minimization.
AB  - To compare a simultaneously optimized continuous minimum rim surface parameter
      between Bruch's membrane opening (BMO) and the internal limiting membrane to the
      standard sequential minimization used for calculating the BMO minimum rim area in
      spectral domain optical coherence tomography (SD-OCT). In this case-control,
      cross-sectional study, 704 eyes of 445 participants underwent SD-OCT of the optic
      nerve head (ONH), visual field testing, and clinical examination. Globally and
      clock-hour sector-wise optimized BMO-based minimum rim area was calculated
      independently. Outcome parameters included BMO-globally optimized minimum rim
      area (BMO-gMRA) and sector-wise optimized BMO-minimum rim area (BMO-MRA). BMO
      area was 1.89 +/- 0.05 mm2. Mean global BMO-MRA was 0.97 +/- 0.34 mm2, mean
      global BMO-gMRA was 1.01 +/- 0.36 mm2. Both parameters correlated with r = 0.995
      (P < 0.001); mean difference was 0.04 mm2 (P < 0.001). In all sectors, parameters
      differed by 3.0-4.2%. In receiver operating characteristics, the calculated area
      under the curve (AUC) to differentiate glaucoma was 0.873 for BMO-MRA, compared
      to 0.866 for BMO-gMRA (P = 0.004). Among ONH sectors, the temporal inferior
      location showed the highest AUC. Optimization strategies to calculate BMO-based
      minimum rim area led to significantly different results. Imposing an additional
      adjacency constraint within calculation of BMO-MRA does not improve diagnostic
      power. Global and temporal inferior BMO-MRA performed best in differentiating
      glaucoma patients.

PMID- 29066840
TI  - Dynamic measurement of near-field radiative heat transfer.
AB  - Super-Planckian near-field radiative heat transfer allows effective heat transfer
      between a hot and a cold body to increase beyond the limits long known for black
      bodies. Until present, experimental techniques to measure the radiative heat flow
      relied on steady-state systems. Here, we present a dynamic measurement approach
      based on the transient plane source technique, which extracts thermal properties
      from a temperature transient caused by a step input power function. Using this
      versatile method, that requires only single sided contact, we measure enhanced
      radiative conduction up to 16 times higher than the blackbody limit on centimeter
      sized glass samples without any specialized sample preparation or
      nanofabrication.

PMID- 29066839
TI  - Calcineurin/P-ERK/Egr-1 Pathway is Involved in Fear Memory Impairment after
      Isoflurane Exposure in Mice.
AB  - Isoflurane exposure adversely influences subsequent fear memory formation in
      mice. Calcineurin (CaN), a phosphatase, prevents the establishment of emotional
      memory by dephosphorylating substrates and inhibiting the expression of learning
      and memory related genes. We investigated whether isoflurane impairment of fear
      memory formation was associated with altered CaN activity and downstream
      phosphorylated-extracellular signal-regulated kinases (p-ERK) and early growth
      response gene-1 (Egr-1) expression in hippocampus and amygdala. We also tested
      whether memory performance can be rescued by the CaN inhibitor FK506. Adult
      C57BL/6 mice were injected FK506 or vehicle after being exposed to 1.3%
      isoflurane or air for 1 h. After a 1 h- recovery, mice underwent classical fear
      conditioning (FC) training. Fear memory were tested 30 min, 48 h and 7 days after
      training. The activity of CaN, and expression of p-ERK and Egr-1 in hippocampus
      and amygdala were analyzed. Isoflurane exposure reduced mice freezing time in
      contextual and tone FC tests 30 min and 48 h after training. Hippocampus and
      amygdala from isoflurane-exposed mice had enhanced CaN activity, reduced p
      ERK/ERK and Egr-1 expression. All these changes in isoflurane-exposed mice were
      attenuated by FK506 treatment. These results indicate calcineurin/p-ERK/Egr-1
      Pathway is involved in fear memory impairment after isoflurane exposure in mice.

PMID- 29066841
TI  - Nomogram for Predicting Cardiovascular Mortality in Incident Peritoneal Dialysis
      Patients: An Observational Study.
AB  - Cardiovascular mortality risk is high for peritoneal dialysis (PD) patients but
      it varies considerably among individuals. There is no clinical tool to predict
      cardiovascular mortality for PD patients yet. Therefore, we developed a
      cardiovascular mortality risk nomogram in a PD patient cohort. We derived and
      internally validated the nomogram in incident adult PD patients randomly assigned
      to a training (N = 918) or a validation (N = 460) dataset. The nomogram was built
      using the LASSO Cox regression model. Increasing age, history of cardiovascular
      disease or diabetes were consistent predictors of cardiovascular mortality. Low
      hemoglobin and serum albumin, high hypersensitive C-reactive protein and
      decreasing 24 hours urine output were identified as non-traditional
      cardiovascular risk predictors. In the validation dataset, the above nomogram
      performed good discrimination (1 year c-statistic = 0.83; 3 year c-statistic =
      0.78) and calibration. This tool can classify patients between those at high risk
      of cardiovascular mortality (high-risk group) and those of low risk (low-risk
      group). Cardiovascular mortality was significantly different in the internal
      validation set of patients for the high-risk group compared to the low-risk group
      (HR 3.77, 2.14-6.64; p < 0.001). This novel nomogram can accurately predict
      cardiovascular mortality risk in incident PD patients.

PMID- 29066843
TI  - Method to Reduce Long-lived Fission Products by Nuclear Transmutations with Fast
      Spectrum Reactors.
AB  - Transmutation of long-lived fission products (LLFPs: 79Se, 93Zr, 99Tc, 107Pd,
      129I, and 135Cs) into short-lived or non-radioactive nuclides by fast neutron
      spectrum reactors without isotope separation has been proposed as a solution to
      the problem of radioactive wastes disposal. Despite investigation of many
      methods, such transmutation remains technologically difficult. To establish an
      effective and efficient transmutation system, we propose a novel neutron
      moderator material, yttrium deuteride (YD2), to soften the neutron spectrum
      leaking from the reactor core. Neutron energy spectra and effective half-lives of
      LLFPs, transmutation rates, and support ratios were evaluated with the continuous
      energy Monte Carlo code MVP-II/MVP-BURN and the JENDL-4.0 cross section library.
      With the YD2 moderator in the radial blanket and shield regions, effective half
      lives drastically decreased from 106 to 102 years and the support ratios reached
      1.0 for all six LLFPs. This successful development and implementation of a
      transmutation system for LLFPs without isotope separation contributes to a the
      ability of fast spectrum reactors to reduce radioactive waste by consuming their
      own LLFPs.

PMID- 29066842
TI  - Screening and identification of critical transcription factors involved in the
      protection of cardiomyocytes against hydrogen peroxide-induced damage by Yixin
      shu.
AB  - Oxidative stress initiates harmful cellular responses, such as DNA damage and
      protein denaturation, triggering a series of cardiovascular disorders. Systematic
      investigations of the transcription factors (TFs) involved in oxidative stress
      can help reveal the underlying molecular mechanisms and facilitate the discovery
      of effective therapeutic targets in related diseases. In this study, an
      integrated strategy which integrated RNA-seq-based transcriptomics techniques and
      a newly developed concatenated tandem array of consensus TF response elements
      (catTFREs)-based proteomics approach and then combined with a network
      pharmacology analysis, was developed and this integrated strategy was used to
      investigate critical TFs in the protection of Yixin-shu (YXS), a standardized
      medical product used for ischaemic heart disease, against hydrogen peroxide
      (H2O2)-induced damage in cardiomyocytes. Importantly, YXS initiated biological
      process such as anti-apoptosis and DNA repair to protect cardiomyocytes from H2O2
      induced damage. By using the integrated strategy, DNA-(apurinic or apyrimidinic
      site) lyase (Apex1), pre B-cell leukemia transcription factor 3 (Pbx3), and five
      other TFs with their functions involved in anti-oxidation, anti-apoptosis and DNA
      repair were identified. This study offers a new understanding of the mechanism
      underlying YXS-mediated protection against H2O2-induced oxidative stress in
      cardiomyocytes and reveals novel targets for oxidative stress-related diseases.

PMID- 29066844
TI  - Treatment of Necrotic Teeth by Apical Revascularization: Meta-analysis.
AB  - Each year ~5.4 million children and adolescents in the United States suffer from
      dental infections, leading to pulp necrosis, arrested tooth-root development and
      tooth loss. Apical revascularization, adopted by the American Dental Association
      for its perceived ability to enable postoperative tooth-root growth, is being
      accepted worldwide. The objective of the present study is to perform a meta
      analysis on apical revascularization. Literature search yielded 22 studies
      following PRISMA with pre-defined inclusion and exclusion criteria. Intraclass
      correlation coefficient was calculated to account for inter-examiner variation.
      Following apical revascularization with 6- to 66-month recalls, root apices
      remained open in 13.9% cases (types I), whereas apical calcification bridge
      formed in 47.2% (type II) and apical closure (type III) in 38.9% cases. Tooth
      root lengths lacked significant postoperative gain among all subjects (p =
      0.3472) or in subgroups. Root-dentin area showed significant increases in type
      III, but not in types I or II cases. Root apices narrowed significantly in types
      II and III, but not in type I patients. Thus, apical revascularization
      facilitates tooth-root development but lacks consistency in promoting root
      lengthening, widening or apical closure. Post-operative tooth-root development in
      immature permanent teeth represents a generalized challenge to regenerate
      diseased pediatric tissues that must grow to avoid organ defects.

PMID- 29066845
TI  - C19, a C-terminal peptide of CKLF1, decreases inflammation and proliferation of
      dermal capillaries in psoriasis.
AB  - Psoriasis is a chronic inflammatory autoimmune disease with undefined etiology.
      Chemokine-like factor 1 (CKLF1), a human cytokine that is a functional ligand for
      CCR4, displays chemotactic activities in a wide spectrum of leukocytes and plays
      an important role in psoriasis development. In previous study, our laboratory
      found that the expression of CKLF1 increased in psoriatic lesions. C19 as a
      CKLF1's C-terminal peptide has been reported to exert inhibitory effects on a
      variety of diseases. However, the protective roles of C19 in endothelial cells
      proliferation and inflammatory cells chemotaxis remain elusive in psoriasis. In
      this study we examined the protective effect of C19 on both the cellular model
      and the animal model. The effects of C19 on endothelial cells proliferation and
      inflammatory cells chemotaxis were investigated in cultured human umbilical vein
      endothelial cells (HUVECs) and imiquimod-induced psoriasiform inflammation of
      BALB/c mice based on techniques including immunohistochemical analysis,
      quantitative real-time PCR (qRT-PCR), western blot, transwell, and EdU assay.
      This study shows that CKLF1-C19 significantly protects against psoriasis by
      inhibiting the infiltration of inflammatory cells and proliferation of
      microvascular cells, possibly via inhibiting MAPK pathways.

PMID- 29066846
TI  - Specific neurophysiological mechanisms underlie cognitive inflexibility in
      inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is highly prevalent. While the
      pathophysiological mechanisms of IBD are increasingly understood, there is a lack
      of knowledge concerning cognitive dysfunctions in IBD. This is all the more the
      case concerning the underlying neurophysiological mechanisms. In the current
      study we focus on possible dysfunctions of cognitive flexibility (task switching)
      processes in IBD patients using a system neurophysiological approach combining
      event-related potential (ERP) recordings with source localization analyses. We
      show that there are task switching deficits (i.e. increased switch costs) in IBD
      patients. The neurophysiological data show that even though the pathophysiology
      of IBD is diverse and wide-spread, only specific cognitive subprocesses are
      altered: There was a selective dysfunction at the response selection level (N2
      ERP) associated with functional alterations in the anterior cingulate cortex and
      the right inferior frontal gyrus. Attentional selection processes (N1 ERP),
      perceptual categorization processes (P1 ERP), or mechanisms related to the
      flexible implementation of task sets and related working memory processes (P3
      ERP) do not contribute to cognitive inflexibility in IBD patients and were
      unchanged. It seems that pathophysiological processes in IBD strongly compromise
      cognitive-neurophysiological subprocesses related to fronto-striatal networks.
      These circuits may become overstrained in IBD when cognitive flexibility is
      required.

PMID- 29066847
TI  - Passive and Active Triaxial Wall Mechanics in a Two-Layer Model of Porcine
      Coronary Artery.
AB  - Triaxial active and passive mechanical properties of coronary arteries are needed
      for understanding arterial mechanics in health and disease. The aim of the study
      was to quantify both active and passive strain energy functions in
      circumferential, axial and radial directions based on the experimental
      measurement. Moreover, a two-layer computational model was used to determine the
      transmural distribution of stresses and strains across the vessel wall. The first
      Piola-Kirchhoff stresses in the three normal directions had the approximate
      relationship as:[Formula: see text]. The two-layer model showed that
      circumferential Cauchy stresses increased significantly from the intima layer to
      the interface between media and adventitia layers (from ~80 to 160 kPa), dropped
      abruptly at the interface (from ~160 to <5 kPa), and increased slightly towards
      the outer boundary of the adventitia layer. In contrast, absolute values of
      radial Cauchy stress decreased continuously from the inner to outer boundaries of
      the vessel wall (from ~11 kPa to zero). Smooth muscle cell contraction
      significantly increased the ratio of radial to circumferential Cauchy stresses at
      the intima-media layer, which had the highest values at the intima layer.

PMID- 29066848
TI  - Stable and ordered amide frameworks synthesised under reversible conditions which
      facilitate error checking.
AB  - ABSTARCT: Covalent organic frameworks (COFs) are network polymers with long-range
      positional order whose properties can be tuned using the isoreticular chemistry
      approach. Making COFs from strong bonds is challenging because irreversible rapid
      formation of the network produces amorphous materials with locked-in disorder.
      Reversibility in bond formation is essential to generate ordered networks, as it
      allows the error-checking that permits the network to crystallise, and so
      candidate network-forming chemistries such as amide that are irreversible under
      conventional low temperature bond-forming conditions have been underexplored.
      Here we show that we can prepare two- and three-dimensional covalent amide
      frameworks (CAFs) by devitrification of amorphous polyamide network polymers
      using high-temperature and high-pressure reaction conditions. In this way we have
      accessed reversible amide bond formation that allows crystalline order to
      develop. This strategy permits the direct synthesis of practically irreversible
      ordered amide networks that are stable thermally and under both strong acidic and
      basic hydrolytic conditions.

PMID- 29066849
TI  - Chemotherapeutic efficacies of a clofazimine and diminazene aceturate combination
      against piroplasm parasites and their AT-rich DNA-binding activity on Babesia
      bovis.
AB  - Recently, we reported that clofazimine (CF) has an anti-piroplasm activity, but
      it could not completely eliminate parasites in the host. The currently available
      anti-piroplasm drug, diminazene aceturate (DA), has sometimes been reported to
      have toxic side effects. In the present study, we evaluated the combination
      treatment with CF and DA against piroplasms both in vitro and in vivo.
      Additionally, mRNA level and DNA amounts were analyzed in CF- and DA-treated
      Babesia bovis by a qPCR. The CF-DA combination had additive effects on Babesia
      bovis, B. bigemina, and B. caballi and synergistic effects on Theileria equi. The
      CF-DA combination chemotherapies against B. microti in mice were more potent than
      their monotherapies. In the CF- and DA-treated B. bovis, CF dose-dependently down
      regulated mRNA level and DNA amounts of extranuclear genes (AT-rich featured),
      whereas DA down-regulated only DNA amounts of extranuclear genes, but those of
      nuclear genes were slightly down- or up-regulated by CF and DA. In conclusion,
      the CF-DA combination has a higher efficiency against piroplasms than CF or DA
      monotherapies. CF and DA might have an AT-rich DNA-binding activity. All results
      suggest that the CF-DA combination chemotherapy will be a better choice to treat
      piroplasmosis instead of DA monotherapy.

PMID- 29066850
TI  - Towards an understanding of spiral patterning in the Sargassum muticum shoot
      apex.
AB  - In plants and parenchymatous brown algae the body arises through the activity of
      an apical meristem (a niche of cells or a single cell). The meristem produces
      lateral organs in specific patterns, referred to as phyllotaxis. In plants, two
      different control mechanisms have been proposed: one is position-dependent and
      relies on morphogen accumulation at future organ sites; the other is a lineage
      based system which links phyllotaxis to the apical cell division pattern. Here we
      examine the apical patterning of the brown alga, Sargassum muticum, which
      exhibits spiral phyllotaxis (137.5 degrees  angle) and an unlinked apical cell
      division pattern. The Sargassum apex presents characteristics of a self
      organising system, similar to plant meristems. In contrast to complex plant
      meristems, we were unable to correlate the plant morphogen auxin with bud
      positioning in Sargassum, nor could we predict cell wall softening at new bud
      sites. Our data suggests that in Sargassum muticum there is no connection between
      phyllotaxis and the apical cell division pattern indicating a position-dependent
      patterning mechanism may be in place. The underlying mechanisms behind the
      phyllotactic patterning appear to be distinct from those seen in plants.

PMID- 29066851
TI  - Interaction Between the Trace Amine-Associated Receptor 1 and the Dopamine D2
      Receptor Controls Cocaine's Neurochemical Actions.
AB  - Recent evidence suggests that the trace amine-associated receptor 1 (TAAR1) plays
      a pivotal role in the regulation of dopamine (DA) transmission and cocaine's
      actions. However, the underlying mechanisms through which TAAR1 activation
      mediates these effects have not yet been elucidated. Here, we used fast-scan
      cyclic voltammetry to measure DA dynamics and explore such mechanisms. We show,
      first, that the full TAAR1 agonist, RO5256390, dose-dependently blocked cocaine
      induced inhibition of DA clearance in slices of the nucleus accumbens. Second,
      subthreshold inhibition of PKA or PKC phosphorylation did not prevent TAAR1
      suppression of cocaine effects whereas subeffective doses of the DA D2 receptor
      antagonist, L-741,626, rescued cocaine's ability to produce changes in DA uptake
      in the presence of full TAAR1 activation, thus indicating that TAAR1 modulation
      of cocaine effects requires simultaneous DA D2 receptor activation. Predictably,
      inhibition of glycogen synthase kinase-3 (GSK-3), which results from activation
      of D2/TAAR1 heterodimers, fully reproduced the inhibitory effects of TAAR1
      activation on cocaine-induced changes in DA transmission. Collectively, the
      present observations reveal that the ability of TAAR1 to regulate cocaine effects
      is linked to cooperative interactions with D2 autoreceptors and associated
      downstream molecular targets converging on GSK-3 and suggest a new mechanism to
      disrupt cocaine neurochemical actions.

PMID- 29066852
TI  - Origins of Common Neural Inputs to Different Compartments of the Extensor
      Digitorum Communis Muscle.
AB  - The extensor digitorum communis (EDC) is a multi-compartment muscle that allows
      dexterous extension of the four digits. However, the level of common input shared
      across different compartments of this muscle is not well understood. We seek to
      systematically characterize the common and independent neural input, originated
      from different levels of the central nervous system, to the different
      compartments. A motor unit (MU) coherence analysis was used to capture the
      different sources of common and independent input, by quantifying the coherence
      of MU discharge between different compartments. The MU activities were obtained
      from decomposition of surface electromyogram recordings. Our results showed that
      the MU coherence across different muscle compartments accounted for only a small
      proportion (<20%) of the total input in the alpha (5-12 Hz) and beta (15-30 Hz)
      bands, but was a major driver (>60%) in the delta (1-4 Hz) band. Additionally,
      cross-compartment coherence between the middle and ring-little fingers tended to
      be higher as compared with other finger combinations. Overall, the common input
      shared across different fingers are found to be at low to moderate levels, in
      comparison with the total input, which allows dexterous control of individual
      digits with some degree of coordinated control of multiple digits.

PMID- 29066853
TI  - Non-invasive quantitative imaging of hepatocellular carcinoma growth in mice by
      micro-CT using liver-targeted iodinated nano-emulsions.
AB  - Hepatocellular carcinoma (HCC) is the only cancer for which non-invasive
      diagnosis is recognized by international guidelines. Contrast agent free
      ultrasound imaging, computed tomography (CT) and/or magnetic resonance imaging
      are techniques used for early detection and confirmation. Clinical evidence
      depicts that CT is 30% less precise as compared to MRI for detection of small
      tumors. In our work, we have reported some novel tools that can enhance the
      sensitivity and precision of CT applied to preclinical research (micro-CT). Our
      system, containing non-toxic nano-droplets loaded with iodine has high
      contrasting properties, liver and hepatocyte specificity and strong liver
      persistence. Micro-CT was performed on HCC model implanted in nude mice by
      intrahepatic injection. Contrast agent was administrated intravenously. This
      method allows an unprecedented high precision of detection, quantitative
      measurement of tumor volume and quantitative follow-up of the tumor development.

PMID- 29066855
TI  - The role of READ1 and KIAA0319 genetic variations in developmental dyslexia:
      testing main and interactive effects.
AB  - Developmental dyslexia (DD) is a complex heritable condition characterized by
      impaired reading abilities. Two well-replicated candidate risk factors are as
      follows: (1) regulatory element associated with dyslexia 1 (READ1), which is
      located in intron 2 of DCDC2 and acts as a binding site for protein regulation of
      DCDC2 expression; and (2) a three-single-nucleotide polymorphism risk haplotype
      spanning KIAA0319. Phylogenetically similar READ1 variants showed synergistic
      effects with the KIAA0319 risk haplotype on reading-related phenotypes in a
      general population sample. Here we examine the association between different
      allele classes in READ1, the KIAA0319 risk haplotype and reading-related traits
      in a cohort of 368 Italian children with DD and their siblings (n=266) by testing
      both main and non-additive effects. We replicated the deleterious main effects
      upon both reading accuracy and speed exerted by the longer READ1 alleles. We
      further supported the interdependence through non-additive, possibly
      antagonistic, effects between READ1 and the KIAA0319 risk haplotype on reading
      accuracy. By suggesting the presence of common biological processes underlying
      reading (dis)ability, these findings represent initial support for a generalist
      effect of the non-additive interdependence between READ1 and the KIAA0319 risk
      haplotype. Moreover, our results confirm that using as much information as
      possible about genetic interdependence among dyslexia-candidate genes can help in
      clinically assessing the individual risk for DD.

PMID- 29066854
TI  - 2SNP heritability and effects of genetic variants for neutrophil-to-lymphocyte
      and platelet-to-lymphocyte ratio.
AB  - Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are
      important biomarkers for disease development and progression. To gain insight
      into the genetic causes of variance in NLR and PLR in the general population, we
      conducted genome-wide association (GWA) analyses and estimated SNP heritability
      in a sample of 5901 related healthy Dutch individuals. GWA analyses identified a
      new genome-wide significant locus on the HBS1L-MYB intergenic region for PLR,
      which replicated in a sample of 2538 British twins. For platelet count, we
      replicated three known genome-wide significant loci in our cohort (at CCDC71L
      PIK3CG, BAK1 and ARHGEF3). For neutrophil count, we replicated the PSMD3 locus.
      For the identified top SNPs, we found significant cis and trans expression
      quantitative trait loci effects for several loci involved in hematological and
      immunological pathways. Linkage Disequilibrium score (LD) regression analyses for
      PLR and NLR confirmed that both traits are heritable, with a polygenetic SNP
      heritability for PLR of 14.1%, and for NLR of 2.4%. Genetic correlations were
      present between ratios and the constituent counts, with the genetic correlation
      (r=0.45) of PLR with platelet count reaching statistical significance. In
      conclusion, we established that two important biomarkers have a significant
      heritable SNP component, and identified the first genome-wide locus for PLR.

PMID- 29066857
TI  - Alcoholic liver disease: Gut-liver axis: PPIs, Enterococcus and promotion of
      alcoholic liver disease.

PMID- 29066856
TI  - Modelling acrylamide acute neurotoxicity in zebrafish larvae.
AB  - Acrylamide (ACR), a type-2 alkene, may lead to a synaptopathy characterized by
      ataxia, skeletal muscles weakness and numbness of the extremities in exposed
      human and laboratory animals. Currently, only the mildly affected patients
      undergo complete recovery, and identification of new molecules with therapeutic
      bioactivity against ACR acute neurotoxicity is urgently needed. Here, we have
      generated a zebrafish model for ACR neurotoxicity by exposing 5 days post
      fertilization zebrafish larvae to 1 mM ACR for 3 days. Our results show that
      zebrafish mimics most of the pathophysiological processes described in humans and
      mammalian models. Motor function was altered, and specific effects were found on
      the presynaptic nerve terminals at the neuromuscular junction level, but not on
      the axonal tracts or myelin sheath integrity. Transcriptional markers of proteins
      involved in synaptic vesicle cycle were selectively altered, and the proteomic
      analysis showed that ACR-adducts were formed on cysteine residues of some
      synaptic proteins. Finally, analysis of neurotransmitters profile showed a
      significant effect on cholinergic and dopaminergic systems. These data support
      the suitability of the developed zebrafish model for screening of molecules with
      therapeutic value against this toxic neuropathy.

PMID- 29066858
TI  - Rilpivirine: The Key for Long-term Success.
AB  - During the past 30 years of antiretroviral therapy, continuous improvements in
      drug discovery have provided increasingly potent and safer antivirals that have
      transformed HIV infection in a chronic illness, rarely fatal. Non-nucleoside
      reverse-transcriptase inhibitors (NNRTIs) are frequently used as part of any
      antiretroviral combination therapy. Side effects and low resistance barrier of fi
      rst-generation NNRTIs (e.g., nevirapine and efavirenz) have been overcome with
      rilpivirine (RPV), and the last NNRTI approved for the treatment of HIV
      infection. The good efficacy, safety profi le, and convenient dosing of RPV
      account for the unique durability of RPV-based regimens. The advent of new oral
      fi xed-dose coformulations of RPV (e.g., along with dolutegravir or with
      tenofovir alafenamide [TAF]/emtricitabine [FTC]) as well as the development of
      long-acting injectable RPV nanoformulations will further expand its therapeutic
      landscape, including RPV use in dual maintenance therapy in HIV-infected patients
      or as pre-exposure prophylaxis in high-risk uninfected individuals.

PMID- 29066859
TI  - Epiretinal membrane and cystoid macular edema as predictive factors of recurrent
      proliferative vitreoretinopathy.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is the most common cause of
      recurrent retinal detachment (RD). We sought to determine the predictive factors
      of recurrent PVR formation and the need for additional vitreoretinal surgical
      intervention after uncomplicated primary RD repair. METHODS: This is a
      retrospective single-center case-control study of consecutive patients with PVR
      formation after uncomplicated RD repair. Logistic regression was used to assess
      factors associated with recurrent PVR formation. RESULTS: Thirty-seven eyes (37
      patients) who had recurrent RD secondary to PVR formation were included. Among
      those, 27 eyes needed one additional surgery, whereas the remainder 10 eyes
      required two or more additional surgeries. In the univariate analysis, patients
      who had cystoid macular edema (CME) after the second surgery were 8.33 times
      (crude odds ratio [COR], 95% confidence interval [CI]: 1.23-56.67, p=0.0302) more
      likely to have recurrent PVR formation compared to those who did not have CME
      after the second surgery. Similarly, those who had epiretinal membrane (ERM)
      after the second surgery were 8.00 times (COR, 95% CI: 1.43-44.92, p=0.0182) more
      likely to have recurrent PVR formation compared to those who did not have ERM
      after the second surgery. In the multivariate analysis, patients who had ERM
      after the second surgery were 8.20 times (adjusted odds ratio [AOR], 95% CI: 1.08
      62.40, p=0.0422) more likely to develop recurrent PVR compared to those who did
      not have ERM after the second surgery, when adjusted for age, sex, and CME after
      the second surgery. CONCLUSION: ERM and CME are potential predictive factors for
      recurrent PVR formation after uncomplicated primary RD repair. Early recognition
      and treatment of ERM and CME may be critical to prevent subsequent PVR formation
      and improve visual outcomes.

PMID- 29066860
TI  - Bilberry extract administration prevents retinal ganglion cell death in mice via
      the regulation of chaperone molecules under conditions of endoplasmic reticulum
      stress.
AB  - PURPOSE: To investigate the effect of bilberry extract anthocyanins on retinal
      ganglion cell (RGC) survival after optic nerve crush. Additionally, to determine
      details of the mechanism of the neuroprotective effect of bilberry extract
      anthocyanins and the involvement of endoplasmic reticulum stress suppression in
      the mouse retina. MATERIALS AND METHODS: Anthocyanins in bilberry extract (100
      mg/kg/day or 500 mg/kg/day) were administrated orally to C57BL/6J mice. The
      expression levels of various molecular chaperones were assessed with quantitative
      reverse-transcription polymerase chain reaction, Western blotting, and
      immunohistochemistry. RGC survival was evaluated by measuring the gene expression
      of RGC markers and counting retrogradely labeled RGCs after optic nerve crush.
      RESULTS: The protein levels of Grp78 and Grp94 increased significantly in mice
      after bilberry extract administration. Increased Grp78 and Grp94 levels were
      detected in the inner nuclear layer and ganglion cell layer of the retina,
      surrounding the RGCs. Gene expression of Chop, Bax, and Atf4 increased in mice
      after optic nerve crush and decreased significantly after oral bilberry extract
      administration. RGC survival after nerve crush also increased with bilberry
      extract administration. CONCLUSION: These results indicate that oral bilberry
      extract administration suppresses RGC death. Bilberry extract administration
      increased Grp78 and Grp94 protein levels, an effect which may underlie the
      neuroprotective effect of bilberry extract after optic nerve crush. Thus,
      bilberry extract has a potential role in neuroprotective treatments for retinal
      injuries, such as those which occur in glaucoma.

PMID- 29066861
TI  - Variability of choroidal and retinal thicknesses in healthy eyes using swept
      source optical coherence tomography - implications for designing clinical trials.
AB  - AIM: The aim was to study the variability of choroidal scleral interface (CSI)
      thickness in healthy subjects and its relevance for designing future studies.
      METHODS: A total of 123 volunteers were imaged using swept-source optical
      coherence tomography. Early treatment diabetic retinopathy grid was used.
      RESULTS: Mean central retinal thickness was 285.85+/-14.53 um and 287.18+/-12.93
      um, and mean central CSI thickness was 273.94+/-77.77 um and 271.19+/-78.85 um
      for the right and left eyes, respectively. Mean retinal and CSI thicknesses
      correlated negatively with age (p=0.023, r=-0.208 and p<0.0001, r=-0.426,
      respectively) and axial length (p=0.016, r=-0.220 and p<0.0001, r=-0.504,
      respectively). To detect a CSI change of at least 112 um, a sample size of 11 or
      36 per group is needed for a single- or double-arm study, respectively
      (alpha=0.05, power =0.90, no loss to follow-up, assuming standard deviation in
      future studies as 100 um). CONCLUSION: Future clinical studies using CSI as end
      point are possible with regard to sample size needed.

PMID- 29066863
TI  - Pharmacokinetic and safety evaluation of MB12066, an NQO1 substrate.
AB  - OBJECTIVE: This study evaluated the pharmacokinetics (PKs) and safety of a newly
      developed beta-lapachone (MB12066) tablet, a natural NAD(P)H:quinone
      oxidoreductase 1 (NQO1) substrate, in healthy male volunteers. METHODS: In a
      randomized, double-blind, multiple-dose, two-treatment study, 100 mg MB12066 or
      placebo was given twice daily for 8 days to groups of eight or three fasted
      healthy male subjects, respectively, followed by serial blood sampling. Plasma
      concentrations for beta-lapachone were determined using liquid chromatography
      tandem mass spectrometry. PK parameters were obtained with non-compartmental
      analysis. Tolerability was assessed based on physical examinations, vital signs,
      clinical laboratory tests, and electrocardiograms. RESULTS: Following a single
      100 mg MB12066 oral dose, maximum plasma concentration (Cmax) of beta-lapachone
      was 3.56+/-1.55 ng/mL, and the median (range) time to reach Cmax was 3 h (2-5 h).
      After the 8 days of 100 mg twice daily repeated dosing was completed, mean
      terminal half-life was determined to be 18.16+/-3.14 h, and the mean area under
      the plasma concentration vs time curve at steady state was 50.44+/-29.68 ng.h/mL.
      Accumulation index was 2.72+/-0.37. No serious adverse events (AEs) were
      reported, and all reported intensities of AEs were mild. CONCLUSION: The results
      demonstrated that MB12066 was safe and well tolerated in healthy volunteers and
      that there were no serious AEs. Accumulation in plasma with twice-daily
      administration was associated with a 2.72 accumulation ratio.

PMID- 29066862
TI  - Localized neuropathic pain: an expert consensus on local treatments.
AB  - BACKGROUND: Pain localization is one of the hallmarks for the choice of first
      line treatment in neuropathic pain. This literature review has been conducted to
      provide an overview of the current knowledge regarding the etiology and
      pathophysiology of localized neuropathic pain (LNP), its assessment and the
      existing topical pharmacological treatments. MATERIALS AND METHODS: Literature
      review was performed using Medline from 2010 to December 2016, and all studies
      involving LNP and treatments were examined. A multidisciplinary expert panel of
      five pain specialists in this article reports a consensus on topical approaches
      that may be recommended to alleviate LNP and on their advantages in clinical
      practice. RESULTS: Successive international recommendations have included topical
      5% lidocaine and 8% capsaicin for LNP treatment. The expert panel considers that
      these compounds can be a first-line treatment for LNP, especially in elderly
      patients and patients with comorbidities and polypharmacy. Regulatory LNP
      indications should cover the whole range of LNP and not be restricted to specific
      etiologies or sites. Precautions for the use of plasters must be followed
      cautiously. CONCLUSION: Although there is a real need for more randomized
      controlled trials for both drugs, publications clearly demonstrate excellent
      risk/benefit ratios, safety, tolerance and continued efficacy throughout long
      term treatment. A major advantage of both plasters is that they have proven
      efficacy and may reduce the risk of adverse events such as cognitive impairment,
      confusion, somnolence, dizziness and constipation that are often associated with
      systemic neuropathic pain treatment and reduce the quality of life. Topical
      modalities also may be used in combination with other drugs and analgesics with
      limited drug-drug interactions.

PMID- 29066864
TI  - Variability of the drug response to nonsteroidal anti-inflammatory drugs
      according to cyclooxygenase-2 genetic polymorphism.
AB  - PURPOSE: Cyclooxygenase (COX) is the main pharmacodynamic target of nonsteroidal
      anti-inflammatory drugs (NSAIDs). We investigated the inhibitory effects on COX-2
      after NSAIDs administration using a lipopolysaccharide (LPS)-derived COX-2
      induction model in whole blood, according to the genotypes of COX-2 single
      nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Seven genotypes of COX-2
      SNPs were selected from public databases and analyzed in 324 healthy subjects.
      Two genotypes showing a high percentage of variability were selected. A clinical
      trial examining pharmacodynamics according to the genotype of two SNPs (rs5275
      and rs689466) was conducted. Twenty subjects were administered a single oral dose
      of 200 mg of celecoxib, and pharmacokinetic and pharmacodynamic analyses were
      performed. RESULTS: In the analysis of the pharmacokinetic parameters,
      significant differences in drug exposure were not investigated for each SNP
      genotype. The pharmacodynamic analysis revealed that the maximum effect of COX-2
      inhibition was achieved at 2.0 hours for all genotypes of COX-2 SNPs after a
      single oral administration of 200 mg celecoxib. The inhibitory effects according
      to the genotype of COX-2 SNPs were investigated, and the area under the effect
      curve of the rs689466 GG genotype was significantly lower than that for the AA or
      AG genotype. CONCLUSION: Our results demonstrated that inhibitory effects of
      celecoxib on COX-2 induction were different according to the genotype of COX-2
      SNPs. In the present study, rs689466 is responsible for the variability of the
      response to celecoxib, suggesting that a subject with the GG genotype of rs689466
      would be more responsive to celecoxib in terms of COX-2 inhibition.

PMID- 29066865
TI  - The roles of epigallocatechin-3-gallate in the treatment of neuropathic pain: an
      update on preclinical in vivo studies and future perspectives.
AB  - Neuropathic pain (NP) is a complex and chronic disease caused by lesions or
      defects of the somatosensory nervous system. The treatments normally used for
      managing NP usually lack efficacy. Several animal models of NP have been
      engineered in order to understand the molecular mechanisms underlying NP and to
      find alternative molecules to use as new therapeutic agents. Preclinical in vivo
      studies identified the epigallocatechin-3-gallate (EGCG), a main active component
      of green tea (Camellia sinensis), as a possible therapeutic molecule for NP
      treatment due to its anti-inflammatory and antioxidant properties. Interestingly,
      it has been shown that EGCG reduced bone cancer pain. The purpose of this article
      is to discuss the potential use of EGCG for control and treatment of NP, by
      reviewing the preclinical studies reported in the literature and by shedding
      light on the potential schemes based on EGCG's application in clinical practices.

PMID- 29066866
TI  - Halofuginone ameliorates inflammation in severe acute hepatitis B virus (HBV)
      infected SD rats through AMPK activation.
AB  - The hepatitis B virus (HBV) has caused acute and chronic liver diseases in ~350
      million infected people worldwide. Halofuginone (HF) is a plant alkaloid which
      has been demonstrated to play a crucial role in immune regulation. Our present
      study explored the function of HF in the immune response of HBV-infected Sprague
      Dawley (SD) rats. Plasmid containing pCDNA3.1-HBV1.3 was injected in SD rats for
      the construction of an acute HBV-infected animal model. Our data showed that HF
      reduced the high concentrations of serum hepatitis B e-antigen, hepatitis B
      surface antigen, and HBV DNA induced by HBV infection. HF also reduced the number
      of T helper (Th)17 cells and the expression of interleukin (IL)-17 compared with
      the pCDNA3.1-HBV1.3 group. Moreover, pro-inflammatory cytokine levels (IL-17, IL
      23, interferon-gamma, and IL-2) were downregulated and anti-inflammatory cytokine
      levels (IL-4 and IL-13) were upregulated by HF. Through further research we found
      that the expression of AMP-activated protein kinase (AMPK) and IKBA which
      suppressed NF-kappaB activation was increased while the expression of p-NF-kappaB
      P65 was decreased in pCDNA3.1-HBV1.3+HF group compared with pCDNA3.1-HBV1.3
      group, indicating that HF may work through the activation of AMPK. Finally, our
      conjecture was further verified by using the AMPK inhibitor compound C, which
      counteracted the anti-inflammation effect of HF, resulting in the decreased
      expression of AMPK, IKBA and increased expression of p-NF-kappaB P65 and reduced
      number of Th17 cells. In our present study, HF was considered as an anti
      inflammatory factor in acute HBV-infected SD rats and worked through AMPK
      mediated NF-kappaB p65 inactivation. This study implicated HF as a potential
      therapeutic strategy for hepatitis B.

PMID- 29066867
TI  - Clinical and pharmacological hallmarks of rifapentine's use in diabetes patients
      with active and latent tuberculosis: do we know enough?
AB  - Rifapentine is a rifamycin derivate approved by the US Food and Drug
      Administration in 1998 for the treatment of active, drug-susceptible tuberculosis
      (TB). In 2014, rifapentine was approved for the treatment of latent TB infection
      in patients at high risk of progression to active disease and is currently under
      evaluation by the European Medicines Agency. Expanding indications of rifapentine
      largely affect diabetes patients, since about one-third of them harbor latent TB.
      Clinical consequences of rifapentine use in this population and potentially
      harmful interactions with hypoglycemic agents are widely underexplored and
      generally considered similar to the ones of rifampicin. Indeed, rifapentine too
      may decrease blood levels of many oral antidiabetics and compete with them for
      protein-binding sites and/or transporters. However, the two drugs differ in
      protein-binding degree, the magnitude of cytochrome P450 induction and auto
      induction, the degree of renal elimination, and so on. Rifapentine seems to be
      more suitable for use in diabetes patients with renal impairment, owing to the
      fact that it does not cause renal toxicity, and it is eliminated via kidneys in
      smaller proportions than rifampicin. On the other hand, there are no data related
      to rifapentine use in patients >65 years, and hypoalbuminemia associated with
      diabetic kidney disease may affect a free fraction of rifapentine to a greater
      extent than that of rifampicin. Until more pharmacokinetic information and
      information on the safety of rifapentine use in diabetic patients and drug-drug
      interactions are available, diabetes in TB patients treated with rifapentine
      should be managed with insulin analogs, and glucose and rifapentine plasma levels
      should be closely monitored.

PMID- 29066868
TI  - Protective effect of DA-9401 in finasteride-induced apoptosis in rat testis:
      inositol requiring kinase 1 and c-Jun N-terminal kinase pathway.
AB  - Finasteride is used to treat male pattern baldness and benign prostatic
      hyperplasia. This study investigated the toxicity of finasteride and recovery by
      DA-9401 using Sprague Dawley (SD) rats. Forty adult male SD rats were assigned to
      four groups: control (CTR), finasteride 1 mg/kg/day (F), finasteride 1 mg/kg + DA
      9401 100 mg/kg/day (F + DA 100) and finasteride 1 mg/kg + DA-9401 200 mg/kg/day
      (F + DA 200). Treatments were by oral delivery once daily for 90 consecutive
      days. The gross anatomical parameters assessed included: genital organ weight;
      vas deferens sperm count and sperm motility; testosterone, dihydrotestosterone
      (DHT) and malondialdehyde levels; and histological and terminal deoxynucleotidyl
      transferase enzyme mediated dUTP nick-end labeling (TUNEL) staining of testis for
      spermatogenic cell density, Johnsen's score and apoptosis. Testicular tissue was
      also used for evaluating endoplasmic reticulum (ER) stress and apoptotic
      proteins. Epididymis weight, seminal vesicle weight, prostate weight, penile
      weight and vas deferens sperm motility showed significant differences between the
      F group and the CTR, F + DA 100 and F + DA 200 groups. There was no significant
      change in the testosterone level. DHT level decreased significantly in the F
      group compared with the CTR group. Testis tissue revealed significant changes in
      spermatogenic cell density, Johnsen's score and apoptotic index. Western blot
      showed significant changes in the ER stress and apoptotic markers. Finasteride
      resulted in reduced fertility and increased ER stress and apoptotic markers,
      which were recovered by administration of DA-9401 in the SD rats.

PMID- 29066869
TI  - Treatment satisfaction with botulinum toxin: a comparison between blepharospasm
      and cervical dystonia.
AB  - BACKGROUND: Differential effects of botulinum toxin (BoNT) treatment in cervical
      dystonia (CD) and blepharospasm (BSP) treatment satisfaction and emotional
      responses to a life with a disabling condition were investigated. Special
      interest was drawn to the course within a BoNT treatment cycle and the effects of
      subjective well-being vs perceived intensity of motor symptoms and quality of
      life. METHODS: A questionnaire was distributed among 372 CD patients and 125 BSP
      patients, recruited from 13 BoNT centers throughout Germany. Items were related
      to dystonic symptoms, BoNT treatment responses and treatment satisfaction,
      quality of life, working situation, and emotional reactions to a life with
      dystonia. RESULTS: CD patients and BSP patients were widely satisfied with BoNT
      treatment, but treatment satisfaction worsened significantly within the treatment
      cycle. Especially CD patients reported that both the dystonic symptoms and the
      effects of BoNT treatment were influenced by emotional factors. Despite good
      overall treatment effects, patients from both groups perceived marked persistence
      of motor symptoms, restrictions of everyday life functions, and reduced quality
      of life. Functional amelioration of motor symptoms and emotional well-being were
      only moderately correlated. About 22% of patients from both groups reported
      mental disorders or emotional disturbances prior to the onset of dystonia.
      CONCLUSION: As numerous psychological factors determine perceived outcome, BoNT
      treatment should be further improved by patient's education strategies enhancing
      behavioral self-control. From the patient's perspective, individual intervals,
      which may avoid exacerbation between injection points, should be considered.
      Moreover, patients at risk, with reduced adherence and poor BoNT outcome, should
      be identified and addressed within psychoeducation.

PMID- 29066870
TI  - Known-group validity of patient-reported outcome instruments and hemophilia joint
      health score v2.1 in US adults with hemophilia: results from the Pain, Functional
      Impairment, and Quality of life (P-FiQ) study.
AB  - BACKGROUND: The Pain, Functional Impairment, and Quality of Life (P-FiQ) study
      was an observational, cross-sectional assessment of the impact of pain on
      functional impairment and quality of life in adults with hemophilia in the United
      States who experience joint pain or bleeding. OBJECTIVE: To describe known-groups
      validity of assessment tools used in the P-FiQ study. PATIENTS AND METHODS:
      Participants completed 5 patient-reported outcome (PRO) instruments (5-level
      EuroQoL 5-dimensional questionnaire [EQ-5D-5L] with visual analog scale [VAS],
      Brief Pain Inventory v2 Short Form [BPI], International Physical Activity
      Questionnaire [IPAQ], Short-Form Health Survey [SF-36v2], and Hemophilia
      Activities List [HAL]) and underwent a musculoskeletal examination (Hemophilia
      Joint Health Score [HJHS]) during a routine clinical visit. RESULTS: P-FiQ
      enrolled 381 adults with hemophilia (median age, 34 years). Participants were
      predominantly white/non-Hispanic (69.2%), 75% had congenital hemophilia A, and
      70.5% had severe hemophilia. Most (n=310) reported bleeding within the past 6
      months (mean [SD] number of bleeds, 7.1 [13.00]). All instruments discriminated
      between relevant known (site- or self-reported) participant groups. Domains
      related to pain on EQ-5D-5L, BPI, and SF-36v2 discriminated self-reported pain
      (acute/chronic/both; P<0.05), domains related to functional impairment on IPAQ,
      SF-36v2, and HAL discriminated self-reported functional impairment
      (restricted/unrestricted; P<0.05), and domains related to mental health on the EQ
      5D-5L and SF-36v2 discriminated self-reported anxiety/depression (yes/no;
      P<0.01). HJHS ankle and global gait domains and global score discriminated self
      reported arthritis/bone/joint problems, percentage of lifetime on prophylaxis,
      current treatment regimen, and hemophilia severity (P<0.01); knee and elbow
      domains discriminated all of these (P<0.01) except for current treatment regimen.
      CONCLUSION: All assessment tools demonstrated known-group validity and may have
      practical applicability in evaluating adults with hemophilia in clinical and
      research settings in the United States.

PMID- 29066871
TI  - REAC regenerative treatment efficacy in experimental chondral lesions: a pilot
      study on ovine animal model.
AB  - Radioelectric asymmetric conveyor (REAC) technology is a platform designed to
      optimize cell polarity. Cell polarity is a universal biological phenomenon that
      is implicated in cell differentiation, proliferation, morphogenesis, aging, and
      rejuvenation. In this work, we investigate a timing and administration protocol
      for tissue optimization regenerative treatment type C, in order to treat aging
      related chondral damage or injuries and gain insights into regenerative processes
      of articular cartilage in humans. The chondral lesion produced in this study in
      an animal model (6 knee joints of 4 adult sheep) was 6 mm in diameter and about 2
      mm deep. These lesions, which did not involve subchondral bone, tend to increase
      in size and depth and are not completely repaired with normal hyaline articular
      cartilage since adult articular cartilage is avascular and has a very slow
      turnover at the cellular and molecular level. Moreover, the hydration of
      articular cartilage is reduced with aging and with decreased mitotic activity,
      synthesis, and population size of chondrocytes. Six months posttreatment, lesions
      appeared filled, though not completely, with newly generated tissue of the light
      opalescent color of healthy articular cartilage, which otherwise covered the
      underlying subchondral bone. The newly formed tissue surface appeared to be quite
      regular. Nearly complete regeneration of subchondral bone occurred, with little
      vascularization and ossification nuclei almost absent. The results of this study
      confirm previous data obtained in vitro on the regenerative effects of REAC
      technology on human normal and osteoarthritic chondrocytes exposed to IL-1beta.
      The present findings indicate that REAC tissue optimization-regenerative
      treatment type C is a promising therapeutic tool among the other REAC
      regenerative treatment protocols for the treatment of cartilage lesions.

PMID- 29066872
TI  - Association of vitamin D receptor gene polymorphisms with diabetic dyslipidemia
      in the elderly male population in North China.
AB  - BACKGROUND: The prevalence of dyslipidemia is rising alarmingly in elderly Han
      Chinese male patients with type 2 diabetes mellitus (T2DM). The genetic factors
      that contribute to the development of diabetic dyslipidemia remain incompletely
      identified. This study was conducted to assess the association between vitamin D
      receptor (VDR) polymorphisms and development of dyslipidemia in the Han elderly
      male population with T2DM in North China. METHODS: A total of 242 T2DM patients
      with dyslipidemia (DH group, n=108) or without dyslipidemia (DO group, n=134) and
      100 controls were genotyped for ApaI, TaqI and FokI single nucleotide
      polymorphisms (SNPs) of the VDR gene using polymerase chain reaction-restriction
      fragment length polymorphism and sequencing. The frequency and distribution of
      the SNPs were compared between cases and controls. RESULTS: The distribution of
      genotypes of VDR-FokI was significantly different between the control and DM
      group (P=0.033), as well as between the control and DH subgroup (P=0.011) but not
      DO subgroup (P=0.111). The frequency of C allele and CC genotype of FokI was
      significantly higher in the DH patients than in the controls (P=0.015 and
      P=0.003, respectively). Logistic regression analysis in a dominant model
      homozygous for the C allele of the FokI SNP showed that CC genotype was
      associated with DH patients (OR =1.797, 95% CI: 1.077-2.999, P=0.025).
      Significant associations of the ApaI and TaqI SNPs with either DO or DH subjects
      were not observed. CONCLUSION: These findings suggest that CC genotype of VDR
      FokI is a risk factor for T2DM patients with dyslipidemia in elderly males in
      North China.

PMID- 29066873
TI  - Application of a computer-based neurocognitive assessment battery in the elderly
      with and without hearing loss.
AB  - INTRODUCTION: Due to demographic changes, the number of people suffering not only
      from dementia illness but also from hearing impairment with the need for hearing
      rehabilitation have increased noticeably. Even with the association between
      hearing, age, and cognitive decline being well known, this issue has so far not
      played an important role in daily clinical Ear Nose Throat settings. The aim of
      the present study was to evaluate the use of a computer-based battery of tests of
      neurocognitive abilities in older patients with and without hearing loss.
      PATIENTS AND METHODS: A total of 120 patients aged 50 years and older were
      enrolled in this prospective clinical study: 40 patients suffered from severe
      bilateral hearing loss and were tested before cochlear implantation and 80
      patients showed normal hearing thresholds between 500 and 4,000 Hz bilaterally.
      The test battery covered a wide range of cognitive abilities such as long- and
      short-term memory, working memory (WM), attention, inhibition, and other
      executive functions. Individuals with severe depression or cognitive impairment
      were excluded. RESULTS: Hearing status was a significant predictor of performance
      on delayed recall (P=0.0082) and verbal fluency after adjusting for age
      (P=0.0016). Age predominantly impacted on inhibition (P=0.0039) and processing
      speed (P<0.0001), whereas WM measured by the Operation Span task (OSPAN) and the
      attention were influenced by both age and hearing. The battery of tests was
      feasible and practical for testing older patients without prior computer skills.
      CONCLUSION: A computerized neurocognitive assessment battery may be a suitable
      tool for the elderly in clinical practice. While it cannot replace a thorough
      neuropsychological examination, it may help to draw the line between cognitive
      and hearing impairment in the elderly and enable the development of individual
      strategies for hearing rehabilitation.

PMID- 29066874
TI  - Optimization of drug therapy in elderly individuals admitted to a geriatric unit.
AB  - BACKGROUND: A substantial share of adverse drug events involves inappropriate
      prescribing (IP). Specialized geriatric units are supposed to pay particular
      attention to prescribing appropriateness and to promoting a higher prescribing
      quality. OBJECTIVE: The objective of this study was to evaluate the reality of
      such assessment and optimization in real life (usual care) in a population of
      elderly individuals admitted to a geriatric unit. METHOD: This is an
      observational study including all older patients admitted to an acute geriatric
      unit over a 6-month period. As part of usual care, the geriatrician is supposed
      to detect potentially inappropriate medication and potential prescribing omission
      using validated tools. The primary outcome was the prevalence rate of therapeutic
      modifications motivated by treatment optimization (stop, switch, or
      introduction). Multivariate logistic regression analyses were performed to
      identify the factors associated with therapeutic discontinuation. RESULTS: A
      total of 216 patients were included. The mean age was 85.7 years. Included
      patients had an average of 7.2+/-3.3 drugs at admission and 5.8+/-2.7 at
      discharge. IP was highly prevalent in our study where about 63% of the patients
      had experienced at least one modification because of overuse. The most commonly
      discontinued medications were drugs used to treat gastroesophageal reflux disease
      and peptic ulcer disease and serotonin reuptake inhibitor antidepressants. The
      most commonly introduced medications were analgesics and warfarin. By using
      multivariate analysis, we found that patient age and number of drugs on admission
      were significantly associated with medication discontinuation during hospital
      stay. CONCLUSION: In this real-life study of all patients admitted to a Geriatric
      Post Emergency Unit, 83% of the patients had a treatment modification during
      hospital stay. The most original result of our study is the clear reduction in
      polypharmacy during hospitalization.

PMID- 29066876
TI  - Comparative study of two different respiratory training protocols in elderly
      patients with chronic obstructive pulmonary disease.
AB  - AIM: The aim of the present study was to compare threshold inspiratory muscle
      training (IMT) and expiratory muscle training (EMT) in elderly male patients with
      moderate degree of COPD. MATERIALS AND METHODS: Forty male patients with moderate
      degree of COPD were recruited for this study. They were randomly divided into two
      groups: the IMT group who received inspiratory training with an intensity ranging
      from 15% to 60% of their maximal inspiratory pressure, and the EMT group who
      received expiratory training with an equal intensity which was adjusted according
      to the maximal expiratory pressure. Both groups received training three times per
      week for 2 months, in addition to their prescribed medications. RESULTS: Both IMT
      and EMT groups showed a significant improvement in forced vital capacity, forced
      expiratory volume in the first second, forced expiratory volume in the first
      second% from the predicted values, and forced vital capacity% from the predicted
      value, with no difference between the groups. Both types of training resulted in
      a significant improvement in blood gases (SaO2%, PaO2, PaCO2, and HCO3), with the
      inspiratory muscle group showing the best results. Both groups showed a
      significant improvement in the 6-min walking distance: an increase of about 25%
      in the inspiratory muscle group and about 2.5% in the expiratory muscle group.
      CONCLUSION: Both IMT and EMT must be implemented in pulmonary rehabilitation
      programs in order to achieve improvements in pulmonary function test, respiratory
      muscle strength, blood oxygenation, and 6-min walking distance.

PMID- 29066875
TI  - Potentially inappropriate medications in hospitalized older patients: a cross
      sectional study using the Beers 2015 criteria versus the 2012 criteria.
AB  - AIM: Polypharmacy and potentially inappropriate medications (PIMs) are prominent
      prescribing issues in elderly patients. The purpose of the study was to
      investigate the prevalence of PIMs identified by the Beers 2015 and 2012 criteria
      in older patients in China and identify the correlates of PIMs. METHODS: This
      retrospective, cross-sectional study was conducted at Peking University First
      Hospital. The Beers 2015 and 2012 criteria were applied to evaluate PIMs among
      hospitalized patients. The associations between PIM use and independent variables
      were analyzed by logistic regression. The differences between PIM use according
      to Beers 2012 and 2015 criteria were calculated using chi-squared and kappa
      tests. RESULTS: A total of 456 patients were analyzed; 244 (53.5%) and 204
      (44.7%) patients had at least one PIM identified by the Beers 2015 and 2012
      criteria, respectively. The most frequent PIMs were proton-pump inhibitors
      (PPIs), benzodiazepines, and benzodiazepine receptor agonists according to the
      Beers 2015 criteria. PIMs identified by the Beers 2015 criteria were associated
      with excessive polypharmacy (OR 1.864, 95% CI 1.210-2.871), a Barthel index <=60
      (OR 1.935, 95% CI 1.056-3.546), and the length of stay (OR 1.066, 95% CI 1.037
      1.097). PIM use increased significantly between two criteria (chi-squared test,
      P<0.001), but good accordance was found between the previous and updated criteria
      (kappa test 0.782, P<0.001). CONCLUSION: Our study showed a high prevalence of
      PIM use in China, which was associated with various correlates. The Beers 2015
      criteria detected significantly more PIMs than the 2012 criteria due to the
      inclusion of PPIs.

PMID- 29066877
TI  - Response to teriparatide in Chinese patients with established osteoporosis:
      osteocalcin and lumbar spine bone-mineral density changes from teriparatide Phase
      III study.
AB  - Teriparatide is the first anabolic agent for osteoporosis, and this analysis
      aimed to understand responses to teriparatide in Chinese patients with
      established osteoporosis in subgroups. In this Phase III study of teriparatide in
      China, 362 patients were randomized at a 2:1 ratio to receive subcutaneous
      teriparatide (20 MUg/day) or intranasal salmon calcitonin (200 IU/day) for 24
      weeks. Teriparatide treatment produced a significantly greater increase in lumbar
      spine bone-mineral density (LS-BMD) in postmenopausal women than calcitonin at
      the 24-week end point. The relationship between osteocalcin (OCN) and LS-BMD was
      evaluated, and the greatest correlation was found between absolute OCN change at
      week 12 and percentage change in LS-BMD for patients in the teriparatide group
      (r=0.24, P<0.001). The correlation weakened at week 24 (r=0.16, P=0.02) and was
      negligibly negative for calcitonin-treated patients. Proportions of patients
      achieving >10 MUg/L absolute OCN change from baseline in the teriparatide- and
      calcitonin-treated groups were 81% and 6% at week 12, respectively (P<0.001).
      Proportions of patients with increased LS-BMD >=3% at week 24 from baseline were
      71% and 35% in the teriparatide- and calcitonin-treated groups, respectively
      (P<0.001). Proportions of patients meeting both criteria were 63% for the
      teriparatide group and 1% for the calcitonin-treated group (P<0.001). Subgroup
      analysis suggested that significant increases in LS-BMD and OCN can be achieved
      in patients receiving teriparatide, regardless of baseline age, LS-BMD, and
      fracture times. The rate of treatment-emergent adverse events in each subgroup
      was similar to the overall analysis.

PMID- 29066878
TI  - Acute exacerbated COPD: room for improvement in key elements of care.
AB  - INTRODUCTION: Hospitalizations because of acute exacerbated COPD (AECOPD) are a
      major burden to patients and the health care system. Interventions during acute
      and post-acute hospital care exist not only to improve short-term outcomes but
      also to prevent future exacerbations and disease progression. We aimed at
      measuring the implementation rates of acute and post-acute hospital care
      interventions for AECOPD. METHODS: We performed 24 months (January 1, 2012, to
      December 31, 2013) retrospective medical chart review of consecutive cases
      hospitalized to one of three public hospitals in the canton of Zurich due to
      AECOPD. Implementation rates of five acute care and seven post-acute care
      interventions were assessed. RESULTS: Data from 263 hospitalizations (61% male,
      mean age 68.5 years, 47% active smokers) were analyzed. The median length of stay
      was 9 days (interquartile range [IQR] 6-12 days). In all, 32% of hospitalizations
      were caused by individuals with previous hospitalizations because of AECOPD.
      Implementation rates of four acute care interventions were >75% (lowest was
      appropriate antibiotic therapy with 56%). Compared to this, implementation rates
      of five post-acute care interventions were <25% (lowest was patient education and
      self-management advice with 2%). CONCLUSION: The results of this audit revealed
      room for improvement mainly in post-acute care interventions for AECOPD.

PMID- 29066880
TI  - Impact of selective and nonselective beta-blockers on the risk of severe
      exacerbations in patients with COPD.
AB  - BACKGROUND: There is conflicting information regarding the effects of selective
      and nonselective beta-blocker treatment in patients with COPD. PARTICIPANTS AND
      METHODS: This nested case-control study used the Taiwan National Health Insurance
      Research Database. We included COPD patients who used inhalation steroid and beta
      blockers between 1998 and 2010. From this cohort, there were 16,067 patients with
      severe exacerbations included in the analysis and 55,970 controls matched on age,
      sex, COPD diagnosis year, and beta-blockers treatment duration by risk set
      sampling. RESULTS: For the selective beta-blocker users, the current users had a
      lower risk of severe exacerbations than the nonusers (odds ratio [OR], 0.90; 95%
      confidence interval [CI], 0.85-0.96). In contrast, for the nonselective beta
      blocker users, the current users had a higher risk of severe acute exacerbations
      than the nonusers (OR, 1.21; 95% CI, 1.14-1.27). A higher risk of severe
      exacerbation during increasing mean daily dose or within about the initial 300
      days was found in nonselective beta-blockers, but not in selective beta-blockers.
      One selective beta-blocker, betaxolol, had a significantly lower risk of severe
      exacerbations (OR, 0.75; 95% CI, 0.60-0.95). Two nonselective beta-blockers
      (labetalol and propranolol) were associated with a significantly higher risk of
      exacerbations (OR, 1.49; 95% CI, 1.32-1.67 for labetalol; OR, 1.16; 95% CI, 1.10
      1.23 for propranolol). CONCLUSION: Selective beta-blockers can be cautiously
      prescribed for patients with COPD and cardiovascular disease (CVD), however,
      nonselective beta-blockers should not be prescribed for patients with COPD.
      Betaxolol may be the preferred choice of suitable selective beta-blocker for
      patients with COPD, however, labetalol and propranolol should be avoided for
      patients with COPD.

PMID- 29066879
TI  - Efficacy of long-term noninvasive positive pressure ventilation in stable
      hypercapnic COPD patients with respiratory failure: a meta-analysis of randomized
      controlled trials.
AB  - INTRODUCTION: The efficacy of long-term noninvasive positive pressure ventilation
      (NPPV) in stable hypercapnic COPD patients with respiratory failure remains
      unclear. The aim of this meta-analysis was to critically assess the efficacy of
      long-term NPPV on mortality, acute exacerbation, exercise capacity, symptoms and
      significant physiological parameters (lung function, respiratory muscle function
      and gas exchange). PATIENTS AND METHODS: We performed an electronic literature
      search using the PubMed, Cochrane Library, Embase, OVID and Chinese Biomedical
      Literature Database in May 2017. Studies comparing treatment effects of NPPV with
      oxygen therapy in stable hypercapnic COPD patients with respiratory failure were
      conducted, and at least one of the following parameters were reviewed: frequency
      of acute exacerbation, mortality, lung function, respiratory muscle function, gas
      exchange, exercise capacity. RESULTS: Seven studies with 810 subjects were
      identified. The partial pressure of arterial carbon dioxide (PaCO2) significantly
      decreased in patients who received long-term NPPV (weighted mean difference [WMD]
      -3.73, 95% CI: -5.83 to -1.64, P=0.0005). No significant difference was found in
      mortality, partial pressure of arterial oxygen (PaO2), frequency of acute
      exacerbation, lung function, respiratory muscle function and exercise capacity.
      The subgroup analysis showed that NPPV significantly improved the survival of
      patients when it was targeted at greatly reducing hypercapnia (WMD 0.35, 95% CI:
      0.19 to 0.64, P=0.0006). CONCLUSION: The results indicate that long-term NPPV
      decreases the PaCO2 of stable hypercapnic COPD patients with respiratory failure
      and improves mortality with the aim of reducing PaCO2.

PMID- 29066881
TI  - Entropy change of biological dynamics in COPD.
AB  - In this century, the rapid development of large data storage technologies, mobile
      network technology, and portable medical devices makes it possible to measure,
      record, store, and track analysis of large amount of data in human physiological
      signals. Entropy is a key metric for quantifying the irregularity contained in
      physiological signals. In this review, we focus on how entropy changes in various
      physiological signals in COPD. Our review concludes that the entropy change
      relies on the types of physiological signals under investigation. For major
      physiological signals related to respiratory diseases, such as airflow, heart
      rate variability, and gait variability, the entropy of a patient with COPD is
      lower than that of a healthy person. However, in case of hormone secretion and
      respiratory sound, the entropy of a patient is higher than that of a healthy
      person. For mechanomyogram signal, the entropy increases with the increased
      severity of COPD. This result should give valuable guidance for the use of
      entropy for physiological signals measured by wearable medical device as well as
      for further research on entropy in COPD.

PMID- 29066882
TI  - Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed
      micelles for targeting anticancer drug control release.
AB  - We have demonstrated a novel drug delivery system to improve the selectivity of
      the current chemotherapy by pH-responsive, polymeric micelle carriers. The
      micelle carriers were prepared by the self-assembly of copolymers containing the
      polybasic poly(2-(diethylamino) ethyl methacrylate) (PDEAEMA) block. The mixed
      copolymers exhibited a comparatively low critical micelle concentration (CMC;
      1.95-5.25 mg/L). The resultant mixed micelles were found to be <100 nm and were
      used to encapsulate the anticancer drug doxorubicin (DOX) with pretty good drug
      loading content (24%) and entrapment efficiency (55%). Most importantly, the
      micelle carrier exhibited a pH-dependent conformational conversion and promoted
      the DOX release at the tumorous pH. Our in vitro studies demonstrated the
      comparable level of DOX-loaded mixed micelle delivery into tumor cells with the
      free DOX (80% of the tumor cells were killed after 48 h incubation). The DOX
      loaded mixed micelles were effective to inhibit the proliferation of tumor cells
      after prolonged incubation. Overall, the pH-responsive mixed micelle system
      provided desirable potential in the controlled release of anticancer
      therapeutics.

PMID- 29066883
TI  - MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid
      polymer hybrid nanoparticles.
AB  - In recent years, there has been increasing interest in developing a
      multifunctional nanoscale platform for cancer monitoring and chemotherapy.
      However, there is still a big challenge for current clinic contrast agents to
      improve their poor tumor selectivity and response. Herein, we report a new kind
      of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle
      (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs
      can simultaneously accomplish diagnostic imaging, and specific targeting and
      controlled release of doxorubicin (DOX). They exhibit good monodispersity,
      excellent size stability, and a well-defined core-shell structure. Paramagnetic
      nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis
      cetylamine have paramagnetic properties with an approximately two-fold
      enhancement in the longitudinal relaxivity compared to clinical used Magnevist.
      For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster
      and enhanced cell uptake in vitro, and exhibited better antitumor effect both in
      vitro and in vivo.

PMID- 29066884
TI  - Trans-resveratrol-loaded nonionic lamellar liquid-crystalline systems:
      structural, rheological, mechanical, textural, and bioadhesive characterization
      and evaluation of in vivo anti-inflammatory activity.
AB  - Resveratrol (Res) is a common phytoalexin present in a few edible materials, such
      as grape skin, peanuts, and red wine. Evidence has shown the beneficial effects
      of Res on human health, which may be attributed to its anti-inflammatory
      activity. However, the poor aqueous solubility of Res limits its therapeutic
      effectiveness. Therefore, the use of nanostructured delivery systems for Res,
      such as liquid-crystalline systems, could be beneficial. In this study, we aimed
      to develop, characterize, and determine the in vivo effectiveness of Res-loaded
      liquid-crystalline systems. Systems containing copaiba balsam oil, polyethylene
      glycol-40 hydrogenated castor oil, and water were designed. Results of polarized
      light microscopy, small-angle X-ray scattering, texture-profile analysis, and
      flow-rheology analysis showed that the Res-loaded liquid-crystalline system had a
      lamellar structure, textural and mechanical (hardness, compressibility, and
      adhesiveness) properties, and behaved as a non-Newtonian fluid, showing
      pseudoplastic behavior upon skin application. Furthermore, all liquid-crystalline
      systems presented bioadhesive properties that may have assisted in maintaining
      the anti-inflammatory activity of Res, since the topical application of the Res
      loaded lamellar mesophase liquid crystals resulted in edema inhibition in a
      carrageenan-induced paw-inflammation mouse model. Therefore, Res-loaded lamellar
      mesophases represent a promising new therapeutic approach for inhibition of skin
      inflammation.

PMID- 29066885
TI  - Asymmetric dumbbell-shaped silver nanoparticles and spherical gold nanoparticles
      green-synthesized by mangosteen (Garcinia mangostana) pericarp waste extracts.
AB  - Mangosteen (Garcinia mangostana) pericarp waste extract was used to synthesize
      gold and silver nanoparticles by a green strategy. The extract was both a
      reducing and stabilizing agent during synthesis. Phytochemical screening of the
      extract was conducted to obtain information regarding the presence/absence of
      primary and secondary metabolites in the extract. The in vitro antioxidant
      activity results demonstrated that the extract had excellent antioxidant
      activity, which was comparable to a standard (butylated hydroxy toluene).
      Spherical gold nanoparticles (gold nanoparticles green synthesized by mangosteen
      pericarp extract [GM-AuNPs]) with an average size of 15.37+/-3.99 to 44.20+/
      16.99 nm were observed in high-resolution transmission electron microscopy (HR
      TEM) images. Most interestingly, the silver nanoparticles (silver nanoparticles
      green synthesized by mangosteen pericarp extract [GM-AgNPs]) had asymmetric
      nanodumbbell shapes where one tail grew from a spherical head. The average head
      size was measured to be 13.65+/-5.07 to 31.08+/-3.99 nm from HR-TEM images. The
      hydrodynamic size of both nanoparticles tended to increase with increasing
      extract concentration. Large negative zeta potentials (-18.92 to -34.77 mV)
      suggested that each nanoparticle solution possessed excellent colloidal
      stability. The reaction yields were 99.7% for GM-AuNPs and 82.8% for GM-AgNPs,
      which were assessed by inductively coupled plasma optical emission spectroscopy.
      A high-resolution X-ray diffraction pattern confirmed the face-centered cubic
      structure of both nanoparticles. Based on phytochemical screening and Fourier
      transform infrared spectra, the hydroxyl functional groups of carbohydrates,
      flavonoids, glycosides, and phenolic compounds were most likely involved in a
      reduction reaction of gold or silver salts to their corresponding nanoparticles.
      The in vitro cytotoxicity (based on a water-soluble tetrazolium assay)
      demonstrated that GM-AgNPs were toxic to both A549 (a human lung cancer cell) and
      NIH3T3 (a mouse fibroblast cell). The cytotoxicity of GM-AgNPs on A549 cells was
      related to apoptotic cell death. However, GM-AuNPs did not show any significant
      cytotoxicity to either cell. These results suggest that GM-AuNPs have the
      potential to be drug delivery vehicles or carriers for pharmaceutical and
      biomedical applications.

PMID- 29066886
TI  - Polysaccharide-based nanoparticles for co-loading mitoxantrone and verapamil to
      overcome multidrug resistance in breast tumor.
AB  - The aim of this study was to evaluate the potential of polyelectrolyte complex
      nanoparticles (PENPs) based on hyaluronic acid/chitosan hydrochloride (HA/HCS)
      for co-loading mitoxantrone (MTO) and verapamil (VRP) to overcome multidrug
      resistance in breast tumors. PENPs co-loaded with MTO and VRP (MTO-VRP-PENPs)
      were affected by the method of preparation, molecular weight of HA, mass ratios
      and initial concentrations of HA/HCS, pH, and drug quantities. Optimized MTO-VRP
      PENPs were ~209 nm in size with a zeta potential of approximately -24 mV.
      Encapsulation efficiencies (%) of MTO and VRP were 98.33%+/-0.27% and 44.21%+/
      8.62%, respectively. MTO and VRP were successfully encapsulated in PENPs in a
      molecular or amorphous state. MTO-VRP-PENPs showed significant cytotoxicity in
      MCF-7/ADR cells in contrast to MTO-loaded PENPs (MTO-PENPs). The reversal index
      of MTO-VRP-PENPs was 13.25 and 10.33 times greater than that of the free MTO and
      MTO-PENPs, respectively. In conclusion, MTO-VRP-PENPs may serve as a promising
      carrier to overcome tumor drug resistance.

PMID- 29066887
TI  - Melatonin potentiates "inside-out" nano-thermotherapy in human breast cancer
      cells: a potential cancer target multimodality treatment based on melatonin
      loaded nanocomposite particles.
AB  - PURPOSE: With the wide recognition of oncostatic effect of melatonin, the current
      study proposes a potential breast cancer target multimodality treatment based on
      melatonin-loaded magnetic nanocomposite particles (Melatonin-MNPs). METHODS:
      Melatonin-MNPs were fabricated by the single emulsion solvent
      extraction/evaporation method. RESULTS: Based on the facilitated transport of
      melatonin by the GLUT overexpressed on the cell membrane, such Melatonin-MNPs can
      be more favorably uptaken by MCF-7 cells compared with the melatonin-free
      nanocomposite particles, which indicates the cancer targeting ability of
      melatonin molecule. Inductive heating can be generated by exposure to the
      Melatonin-MNPs internalized within cancer cells under alternative magnetic field,
      so as to achieve the "inside-out" magnetic nano-thermotherapy. In addition to
      demonstrating the superior cytotoxic effect of such nano-thermotherapy over the
      conventional exogenous heating by metal bath, more importantly, the sustainable
      release of melatonin from the Melatonin-MNPs can be greatly promoted upon
      responsive to the magnetic heating. The multimodality treatment based on
      Melatonin-MNPs can lead to more significant decrease in cell viability than any
      single treatment, suggesting the potentiated effect of melatonin on the cytotoxic
      response to nano-thermotherapy. CONCLUSION: This study is the first to fabricate
      the precisely engineered melatonin-loaded multifunctional nanocomposite particles
      and demonstrate the potential in breast cancer target multimodality treatment.

PMID- 29066888
TI  - Drug delivery system based on dendritic nanoparticles for enhancement of
      intravesical instillation.
AB  - Intravesical instillation of antitumor agents following transurethral resection
      of bladder tumors is the standard strategy for the treatment of superficial
      bladder cancers. However, the efficacy of current intravesical instillation is
      limited partly due to the poor permeability of the urothelium. We therefore aimed
      to develop a high-penetrating, target-releasing drug delivery system to improve
      the efficacy of intravesical instillation. PAMAM, a dendrimer, were conjugated
      with polyethylene glycol (PEG) to form PEG-PAMAM complex as a nanocarrier.
      Doxorubicin (DOX) was then encapsulated into PEG-PAMAM to generate DOX-loaded PEG
      PAMAM nanoparticles (PEG-PAMAM-DOX). Our results indicated that the PEG-PAMAM was
      a stable nanocarrier with small size and great biosafety. The release of DOX from
      PEG-PAMAM-DOX was sluggish but could be effectively triggered in an acid
      microenvironment (pH =5.0). As a drug carrier, PEG-PAMAM could penetrate mice
      bladder urothelium effectively and increase the amount of DOX within the bladder
      wall after intravesical instillation. The antitumor effect of PEG-PAMAM-DOX was
      evaluated using an orthotopic bladder cancer model in mice. Compared to free DOX,
      PEG-PAMAM-DOX showed significantly improved efficacy of DOX for intravesical
      instillation with limited side effects. In conclusion, we successfully developed
      a PEG-PAMAM-based drug delivery system to enhance the antitumor effect of
      intravesical instillation.

PMID- 29066889
TI  - Facile synthesis of N-rich carbon quantum dots from porphyrins as efficient
      probes for bioimaging and biosensing in living cells.
AB  - N-rich metal-free and metal-doped carbon quantum dots (CQDs) have been prepared
      through one-step hydrothermal method using tetraphenylporphyrin or its transition
      metal (Pd or Pt) complex as precursor. The structures and morphology of the as
      prepared nanoparticles were analyzed by X-ray diffraction, high-resolution
      transmission electron microscopy, X-ray photoelectron spectroscopy, and Fourier
      transform infrared spectra. Three kinds of nanocomposites show similar structures
      except for the presence of metal ions in Pd-CQDs and Pt-CQDs indicated by X-ray
      photoelectron spectroscopy. All of them display bright blue emission upon
      exposure to ultraviolet irradiation. The CQDs exhibit typical excitation
      dependent emission behavior, with the emission quantum yield of 10.1%, 17.8%, and
      15.2% for CQDs, Pd-CQDs, and Pt-CQDs, respectively. Moreover, the CQDs, Pd-CQDs,
      and Pt-CQDs could serve as fluorescent probes for the specific and sensitive
      detection of Fe3+ ions in aqueous solution. The low cytotoxicity of CQDs is
      demonstrated by MTT assay against HeLa cells. Therefore, the CQDs can be used as
      efficient probes for cellular multicolor imaging and fluorescence sensors for the
      detection of Fe3+ ions due to their low toxicity, excellent biocompatibility, and
      low detection limits. This work provides a new route to synthesize highly
      luminescent N-rich metal-free or metal-doped CQDs for multifunctional
      applications.

PMID- 29066890
TI  - Hydrogel-embedded nanocrystalline hydroxyapatite granules (elastic blocks) based
      on a cross-linked polyvinylpyrrolidone as bone grafting substitute in a rat tibia
      model.
AB  - PURPOSE: The aim of this study was to examine the in vivo characteristics and
      levels of integration and degradation of a ready-to-use bone grafting block with
      elastic properties (elastic block) for the use in surgery. MATERIALS AND METHODS:
      Thirty-six male Wistar rats underwent surgical creation of a well-defined bone
      defect in the tibia. All created defects - one per animal - were filled with an
      unsintered nanocrystalline hydroxyapatite embedded either with a non-cross-linked
      hydrogel carrier (CONT, n=18) or a cross-linked hydrogel carrier (elastic block
      [EB], n=18) based on polyvinylpyrrolidone (PVP) and silica sol, respectively. The
      animals were killed after 12 (n=12), 21 (n=12) and 63 days (n=12). The bone
      formation and defect healing were quantified by histomorphometric measurements
      made in paraffin sections. Additionally, immunohistochemical (tartrate-resistant
      acid phosphatase [TRAP] and alkaline phosphatase [aP]), antibody-based
      examinations (CD68) and energy-dispersive x-ray scattering measurements of silica
      atom concentration were carried out. RESULTS: A larger remaining bone defect area
      overall was observed in EB after 12 days and 21 days. After 63 days, similar
      areas of remaining bone defects were found. The amount of the remaining carrier
      material in EB overall was higher at all times. In CONT no residual carrier
      material was found at 12 days and later. CD68 analyses showed significantly lower
      level of CD68-positive marked cells after 21 days in CONT, and nonsignificant
      differences at 12 and 63 days, respectively. Additionally, a significantly higher
      level of aP-positive marked cells was observed in CONT after 12 days. Later on,
      the levels of aP-positive marked cells were slightly higher in EB (21 and 63
      days). Furthermore, no significant differences regarding the level of TRAP
      positive marked cells in each group were observed. CONCLUSION: The bone
      substitute (EB) with the cross-linked PVP-based hydrogel carrier leads at the
      beginning to a higher amount of remaining carrier material and remaining bone
      substitute. This delayed degradation is supposed to be the reason for the
      observed lower level of bone remodeling and is caused by the irradiation changes
      (cross links) in the structure in PVP.

PMID- 29066892
TI  - Bioresponsive cancer-targeted polysaccharide nanosystem to inhibit angiogenesis.
AB  - With many desirable features, such as being more effective and having multiple
      effects, antiangiogenesis has become one of the promising cancer treatments. The
      aim of this study was to design and synthesize a new targeted bioresponsive
      nanosystem with antiangiogenesis properties. The mUPR@Ru(POP) nanosystem was
      constructed by the polymerization of Ulva lactuca polysaccharide and N-isopropyl
      acrylamide, decorated with methoxy polyethylene glycol and Arg-Gly-Asp peptide,
      and encapsulated with anticancer complex [Ru(phen)2p-MOPIP](PF6)2.2H2O. The
      nanosystem was both pH responsive and targeted. Therefore, the cellular uptake of
      the drug was greatly improved. Moreover, the mUPR@Ru(POP) had strong suppressive
      effects against vascular endothelial growth factor (VEGF)-induced angiogenesis
      through apoptosis. The mUPR@Ru(POP) significantly inhibited VEGF-induced human
      umbilical vein endothelial cell migration, invasion, and tube formation. These
      findings have presented new insights into the development of antiangiogenesis
      drugs.

PMID- 29066891
TI  - Enhanced anticancer activity and oral bioavailability of ellagic acid through
      encapsulation in biodegradable polymeric nanoparticles.
AB  - Despite the fact that various studies have investigated the clinical relevance of
      ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy,
      little has been reported regarding the efficient strategy for improving its oral
      bioavailability. In this study, we report the formulation of EA-loaded
      nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as
      bioavailability after oral administration. Poly(epsilon-caprolactone) (PCL) was
      selected as the biodegradable polymer for the formulation of EA-NPs through the
      emulsion-diffusion-evaporation technique. The obtained NPs have been
      characterized by measuring particle size, zeta potential, Fourier transform
      infrared, differential scanning calorimetry, and X-ray diffraction. The
      entrapment efficiency and the release profile of EA was also determined. In vitro
      cellular uptake and cytotoxicity of the obtained NPs were evaluated using Caco-2
      and HCT-116 cell lines, respectively. Moreover, in vivo study has been performed
      to measure the oral bioavailability of EA-NPs compared to free EA, using New
      Zealand white rabbits. NPs with distinct shape were obtained with high entrapment
      and loading efficiencies. Diffusion-driven release profile of EA from the
      prepared NPs was determined. EA-NP-treated HCT-116 cells showed relatively lower
      cell viability compared to free EA-treated cells. Fluorometric imaging revealed
      the cellular uptake and efficient localization of EA-NPs in the nuclear region of
      Caco-2 cells. In vivo testing revealed that the oral administration of EA-NPs
      produced a 3.6 times increase in the area under the curve compared to that of EA.
      From these results, it can be concluded that incorporation of EA into PCL as NPs
      enhances its oral bioavailability and activity.

PMID- 29066893
TI  - Application of multifunctional targeting epirubicin liposomes in the treatment of
      non-small-cell lung cancer.
AB  - Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in
      a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels,
      limited killing of tumor cells, and severe systemic toxicity. Herein, we
      developed a kind of multifunctional targeting epirubicin liposomes to enhance
      antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on
      liposomal surface for obtaining a receptor-mediated targeting effect, and
      honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis
      and eliminating VM channels. In vitro cellular assays showed that multifunctional
      targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect
      on Lewis lung tumor cells but also showed the most efficient inhibition on VM
      channels. Action mechanism studies showed that multifunctional targeting
      epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK
      and activate apoptotic enzyme caspase 3. In vivo results exhibited that
      multifunctional targeting epirubicin liposomes could accumulate selectively in
      tumor site and display an obvious antitumor efficacy. In addition, no significant
      toxicity of blood system and major organs was observed at a test dose. Therefore,
      multifunctional targeting epirubicin liposomes may provide a safe and efficient
      therapy strategy for NSCLC.

PMID- 29066894
TI  - Poly((D,L)lactic-glycolic)acid-star glucose nanoparticles for glucose transporter
      and hypoglycemia-mediated tumor targeting.
AB  - Poly((D,L)lactic-glycolic)acid-star glucose (PLGA-Glc) polymer-based
      nanoparticles (NPs) were fabricated for tumor-targeted delivery of docetaxel
      (DCT). NPs with an approximate mean diameter of 241 nm, narrow size distribution,
      negative zeta potential, and spherical shape were prepared. A sustained drug
      release pattern from the developed NPs was observed for 13 days. Moreover, drug
      release from PLGA-Glc NPs at acidic pH (endocytic compartments and tumor regions)
      was significantly improved compared with that observed at physiological pH
      (normal tissues and organs). DCT-loaded PLGA-Glc NPs (DCT/PLGA-Glc NPs) exhibited
      an enhanced antiproliferation efficiency rather than DCT-loaded PLGA NPs
      (DCT/PLGA NPs) in Hep-2 cells, which can be regarded as glucose transporters
      (GLUTs)-positive cells, at >=50 ng/mL DCT concentration range. Under glucose
      deprived (hypoglycemic) conditions, the cellular uptake efficiency of the PLGA
      Glc NPs was higher in Hep-2 cells compared to that observed in PLGA NPs. Cy5.5
      loaded NPs were prepared and injected into a Hep-2 tumor-xenografted mouse model
      for in vivo near-infrared fluorescence imaging. The PLGA-Glc NPs group exhibited
      higher fluorescence intensity in the tumor region than the PLGA NPs group. These
      results imply that the PLGA-Glc NPs have active tumor targeting abilities based
      on interactions with GLUTs and the hypoglycemic conditions in the tumor region.
      Therefore, the developed PLGA-Glc NPs may represent a promising tumor-targeted
      delivery system for anticancer drugs.

PMID- 29066895
TI  - Evaluation of antibacterial, angiogenic, and osteogenic activities of green
      synthesized gap-bridging copper-doped nanocomposite coatings.
AB  - Titanium (Ti) and its alloys have been widely used in clinics for years. However,
      their bio-inert surface challenges application in patients with compromised
      surgical conditions. Numerous studies were conducted to modify the surface
      topography and chemical composition of Ti substrates, for the purpose of
      obtaining antibacterial, angiogenic, and osteogenic activities. In this study,
      using green electrophoretic deposition method, we fabricated gap-bridging
      chitosan-gelatin (CSG) nanocomposite coatings incorporated with different amounts
      of copper (Cu; 0.01, 0.1, 1, and 10 mM for Cu I, II, III, and IV groups,
      respectively) on the Ti substrates. Physicochemical characterization of these
      coatings confirmed that Cu ions were successfully deposited into the coatings in
      a metallic status. After rehydration, the coatings swelled by 850% in weight.
      Mechanical tests verified the excellent tensile bond strength between Ti
      substrates and deposited coatings. All Cu-containing CSG coatings showed
      antibacterial property against both Gram-negative Escherichia coli and Gram
      positive Staphylococcus aureus. The antibacterial property was positively
      correlated with the Cu concentration. In vitro cytocompatibility evaluation
      demonstrated that activities of bone marrow stromal cells were not impaired on Cu
      doped coatings except for the Cu IV group. Moreover, enhanced angiogenic and
      osteogenic activities were observed on Cu II and Cu III groups. Overall, our
      results suggested that Cu-doped CSG nanocomposite coating is a promising
      candidate to functionalize Ti materials with antibacterial, angiogenic, and
      osteogenic properties.

PMID- 29066896
TI  - Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and
      multiple arms of the innate immune response in lymph nodes.
AB  - In this study, we suggest a designer vaccine adjuvant that can mimic the drainage
      of pathogens into lymph nodes and activate innate immune response in lymph nodes.
      By the amination of multivalent carboxyl groups in poly-(gamma-glutamic acid)
      (gamma-PGA) nanomicelles, the size was reduced for rapid entry into lymphatic
      vessels, and the immunologically inert nanomicelles were turned into potential
      activators of inflammasomes. Aminated gamma-PGA nanomicelles (aPNMs) induced
      NLRP3 inflammasome activation and the subsequent release of proinflammatory IL
      1beta. The NLRP3-dependent inflammasome induction mechanism was confirmed through
      enzyme (cathepsin B and caspase-1) inhibitors and NLRP3 knockout mice model.
      After the aPNMs were combined with a clinically evaluated TLR3 agonist,
      polyinosinic-polycytidylic acid sodium salt (aPNM-IC), they triggered multiple
      arms of the innate immune response, including the secretion of pro-inflammatory
      cytokines by both inflammasomes and an inflammasome-independent pathway and the
      included type I interferons.

PMID- 29066897
TI  - An annotated corpus with nanomedicine and pharmacokinetic parameters.
AB  - A vast amount of data on nanomedicines is being generated and published, and
      natural language processing (NLP) approaches can automate the extraction of
      unstructured text-based data. Annotated corpora are a key resource for NLP and
      information extraction methods which employ machine learning. Although corpora
      are available for pharmaceuticals, resources for nanomedicines and nanotechnology
      are still limited. To foster nanotechnology text mining (NanoNLP) efforts, we
      have constructed a corpus of annotated drug product inserts taken from the US
      Food and Drug Administration's Drugs@FDA online database. In this work, we
      present the development of the Engineered Nanomedicine Database corpus to support
      the evaluation of nanomedicine entity extraction. The data were manually
      annotated for 21 entity mentions consisting of nanomedicine physicochemical
      characterization, exposure, and biologic response information of 41 Food and Drug
      Administration-approved nanomedicines. We evaluate the reliability of the manual
      annotations and demonstrate the use of the corpus by evaluating two state-of-the
      art named entity extraction systems, OpenNLP and Stanford NER. The annotated
      corpus is available open source and, based on these results, guidelines and
      suggestions for future development of additional nanomedicine corpora are
      provided.

PMID- 29066899
TI  - Sex differences in obesity and cognitive function in a cognitively normal aging
      Chinese Han population.
AB  - BACKGROUND: Sex differences in Alzheimer's disease and mild cognitive impairment
      have been well recognized. However, sex differences in cognitive function and
      obesity in cognitively normal aging Chinese Han population have not attracted
      much attention. OBJECTIVE: The aim of this study was to investigate the
      relationship between sex, obesity, and cognitive function in an elderly Chinese
      population with normal cognitive function. SUBJECTS AND METHODS: A total of 228
      cognitively normal aging participants (males/females =93/135) entered this study.
      Their general demographic information (sex, age, and education) was collected by
      standardized questionnaire. Apolipoprotein E (APOE) genotype and serum lipid
      levels were measured. The Montreal Cognitive Assessment (MoCA) was used to assess
      participants' cognitive function. RESULTS: The prevalence of obesity in elderly
      women (18/133, 13.5%) was significantly higher than that in men (5/92, 5.4%,
      P=0.009). Regression analyses showed that obesity was associated with drinking
      alcohol (OR =13.695, P=0.045) and triglyceride (OR =1.436, P=0.048) in women and
      limited to low-density lipoprotein (OR =11.829, P=0.023) in men. Women performed
      worse on the naming score for MoCA than men (P<0.01). Stepwise linear regression
      analysis showed that education (t=3.689, P<0.001) and smoking (t=2.031, P=0.045)
      were related to the score of naming in female, while high-density lipoprotein (t=
      2.077, P=0.041) was related to the score of naming in male; however, no
      correlation was found between body mass index and cognitive function in both male
      and female (P>0.05). CONCLUSION: Our finding suggests that there are significant
      sex differences in obesity and specific cognitive domains in aging Chinese Han
      population with normal cognitive function.

PMID- 29066898
TI  - Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a
      suitable model for evaluating cytotoxicity- and differentiation-mediated cancer
      therapy.
AB  - BACKGROUND: Silver nanoparticles (AgNPs) exhibit strong antibacterial and
      anticancer activity owing to their large surface-to-volume ratios and
      crystallographic surface structure. Owing to their various applications,
      understanding the mechanisms of action, biological interactions, potential
      toxicity, and beneficial effects of AgNPs is important. Here, we investigated the
      toxicity and differentiation-inducing effects of AgNPs in teratocarcinoma stem
      cells. MATERIALS AND METHODS: AgNPs were synthesized and characterized using
      various analytical techniques such as UV-visible spectroscopy, X-ray diffraction,
      energy-dispersive X-ray spectroscopy, and transmission electron microscopy. The
      cellular responses of AgNPs were analyzed by a series of cellular and biochemical
      assays. Gene and protein expressions were analyzed by reverse transcription
      quantitative polymerase chain reaction and western blotting, respectively.
      RESULTS: The AgNPs showed typical crystalline structures and spherical shapes
      (average size =20 nm). High concentration of AgNPs induced cytotoxicity in a dose
      dependent manner by increasing lactate dehydrogenase leakage and reactive oxygen
      species. Furthermore, AgNPs caused mitochondrial dysfunction, DNA fragmentation,
      increased expression of apoptotic genes, and decreased expression of
      antiapoptotic genes. Lower concentrations of AgNPs induced neuronal
      differentiation by increasing the expression of differentiation markers and
      decreasing the expression of stem cell markers. Cisplatin reduced the viability
      of F9 cells that underwent AgNPs-induced differentiation. CONCLUSION: The results
      showed that AgNPs caused differentially regulated cytotoxicity and induced
      neuronal differentiation of F9 cells in a concentration-dependent manner.
      Therefore, AgNPs can be used for differentiation therapy, along with
      chemotherapeutic agents, for improving cancer treatment by targeting specific
      chemotherapy-resistant cells within a tumor. Furthermore, understanding the
      molecular mechanisms of apoptosis and differentiation in stem cells could also
      help in developing new strategies for cancer stem cell (CSC) therapies. The
      findings of this study could significantly contribute to the nanomedicine because
      this study is the first of its kind, and our results will lead to new strategies
      for cancer and CSC therapies.

PMID- 29066901
TI  - Increased risk of pernicious anemia following scabies: a nationwide population
      based matched-cohort study.
AB  - OBJECTIVES: Scabies is a common and annoying disorder. Pernicious anemia (PA) is
      a serious disease which, when untreated, leads to death. Mounting evidence
      suggests that immune-mediated inflammatory processes play a role in the
      pathophysiology of both diseases. The relationship between these two diseases has
      not been investigated. We conducted this study to explore the potential
      relationship between scabies and PA. MATERIALS AND METHODS: This nationwide,
      population-based study was conducted using the National Health Insurance Research
      Database of Taiwan. In total, 5,407 patients with scabies were identified as a
      study group and 20,089 matched patients were randomly selected as a control
      group. We tracked patients in both groups for a 7-year period to identify the
      incidence of PA. The demographic characteristics and comorbidities of the
      patients were analyzed, and Cox proportional hazards regression was used to
      calculate the hazard ratios for PA. RESULTS: Of the 25,496 patients in this
      study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7
      year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of
      20,089 (0.6%) from the control group. Patients with scabies had a higher risk of
      subsequent PA, with a crude hazard ratio of 2.368. After adjusting for
      covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09
      2.08). CONCLUSION: This study demonstrated an increased risk of PA (adjusted
      hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory
      processes may contribute to this association. Further studies are warranted to
      investigate the entire pathological mechanisms between these two diseases.
      Physicians should pay attention to patients with history of scabies presented
      with anemia. Further confirmative tests of PA may contribute to correct diagnosis
      and initiation of vitamin B12 supplement.

PMID- 29066900
TI  - Abnormal functional connectivity of the posterior cingulate cortex is associated
      with depressive symptoms in patients with Alzheimer's disease.
AB  - BACKGROUND: Depressive symptoms are significant and very common psychiatric
      complications in patients with Alzheimer's disease (AD), which can aggravate the
      decline in social function. However, changes in the functional connectivity (FC)
      of the brain in AD patients with depressive symptoms (D-AD) remain unclear.
      OBJECTIVE: To investigate whether any differences exist in the FC of the
      posterior cingulate cortex (PCC) between D-AD patients and non-depressed AD
      patients (nD-AD). MATERIALS AND METHODS: We recruited 15 D-AD patients and 17 age
      , sex-, educational level-, and Mini-Mental State Examination (MMSE)-matched nD
      AD patients to undergo tests using the Neuropsychiatric Inventory, Hamilton
      Depression Rating Scale, and 3.0T resting-state functional magnetic resonance
      imaging. Bilateral PCC were selected as the regions of interest and between-group
      differences in the PCC FC network were assessed using Student's t-test. RESULTS:
      Compared with the nD-AD group, D-AD patients showed increased PCC FC in the right
      amygdala, right parahippocampus, right superior temporal pole, right middle
      temporal lobe, right middle temporal pole, and right hippocampus (AlphaSim
      correction; P<0.05). In the nD-AD group, MMSE scores were positively correlated
      with PCC FC in the right superior temporal pole and right hippocampus (false
      discovery rate corrected; P<0.05). CONCLUSION: Differences were detected in PCC
      FC between nD-AD and D-AD patients, which may be related to depressive symptoms.
      Our study provides a significant enhancement to our understanding of the
      functional mechanisms underlying D-AD.

PMID- 29066902
TI  - Effects of sevoflurane versus propofol on cerebrovascular reactivity to carbon
      dioxide during laparoscopic surgery.
AB  - PURPOSE: Cerebrovascular reactivity to carbon dioxide (CVR-CO2) reflects
      cerebrovascular reserve capacity, which is important in many brain disorders,
      including cerebrovascular and Alzheimer's diseases. Meanwhile, there is a
      relationship between CVR-CO2 and cognitive function. Therefore, the study is
      aimed at investigating the effects of sevoflurane versus propofol on CVR-CO2
      during laparoscopic surgery, as well as the role of CVR-CO2 on cognitive function
      during perioperative period. PATIENTS AND METHODS: Eighty-eight patients, aged 18
      65 years undergoing elective laparoscopic cholecystectomy, were randomly assigned
      to group S and group P. The patients in group S were induced with propofol and
      maintained with sevoflurane. The patients in group P were induced and maintained
      with propofol (target-controlled infusion). Remifentanil was given to both
      groups. CVR-CO2 at baseline (before induction), before pneumoperitoneum and
      during pneumoperitoneum, as well as Mini-Mental State Examination scores at
      baseline and 24 hours after surgery were recorded. RESULTS: In group S, CVR-CO2
      before and during pneumoperitoneum increased significantly compared with baseline
      (P<0.05). In group P, CVR-CO2 before pneumoperitoneum increased significantly
      (P<0.05), but CVR-CO2 during pneumoperitoneum was not different compared with
      baseline. In either group, there was no significant correlation between mean
      blood pressure and CVR-CO2 during surgery, and there was no significant
      difference between Mini-Mental State Examination scores at baseline and 24 hours
      after surgery. CONCLUSION: Sevoflurane could maintain CVR-CO2 at a higher level
      during pneumoperitoneum in surgery. Therefore, in patients with impaired
      cerebrovascular reserve capacity, inhaled anesthetic could be a priority strategy
      for anesthesia maintenance to improve the compensatory vasodilation ability of
      cerebral small vessels.

PMID- 29066903
TI  - Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed
      complication? A systematic review.
AB  - Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several
      clinical trials have established both the beneficial effect of steroids in
      Duchenne muscular dystrophy and the well-known risk of side effects associated
      with their daily use. For many years it has been known that steroids associated
      with ambulation loss lead to obesity and also damage the bone structure resulting
      in the bone density reduction and increased incidence of bone fractures and fat
      embolism syndrome, an underdiagnosed complication after fractures. Fat embolism
      syndrome is characterized by consciousness disturbance, respiratory failure and
      skin rashes. The use of steroids in Duchenne muscular dystrophy may result in
      vertebral fractures, even without previous trauma. Approximately 25% of patients
      with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of
      fractures have a chance to develop fat embolism syndrome. As the patients with
      Duchenne muscular dystrophy have progressive cardiac and respiratory muscle
      dysfunction, the fat embolism may be unnoticed clinically and may result in
      increased risk of death and major complications. Different treatments and
      prevention measures of fat embolism have been proposed; however, so far, there is
      no efficient therapy. The prevention, early diagnosis and adequate symptomatic
      treatment are of paramount importance. The fat embolism syndrome should always be
      considered in patients with Duchenne muscular dystrophy presenting with
      fractures, or an unexplained and sudden worsening of respiratory and cardiac
      symptoms.

PMID- 29066905
TI  - A rare case of lung carcinoma acquires multidrug-resistant Klebsiella pneumoniae
      pneumonia radiologically mimicking metastasis caused by nivolumab therapy
      associated neutropenia.
AB  - Nosocomial infections by Klebsiella pneumoniae, especially those due to multidrug
      resistant strains, are being increasingly detected. In this report, we present
      the case of a 63-year-old man with lung squamous carcinoma who received nivolumab
      therapy due to failure of first-line chemotherapy. This report also demonstrates
      an association of nivolumab therapy and neutropenia, and supports the use of a
      combination of tigecycline and meropenem in managing hospitalization-acquired
      pneumonia caused by multidrug-resistant K. pneumoniae. It also implicates that a
      further evaluation is required in lung cancer patients with a suspected
      metastatic or recurrent carcinoma, and an antibiotic therapy is valuable in
      ruling out a potential lung infection since a risk of hospitalization-acquired
      pneumonia may exist.

PMID- 29066906
TI  - Factors associated with high brachial-ankle pulse wave velocity in non
      hypertensive and appropriately treated hypertensive patients with atherosclerotic
      risk factors.
AB  - While pulse wave velocity (PWV) correlates with blood pressure (BP), its extent
      differs between patients, and some cases of high PWV in normotensives are
      present. Moreover, PWV frequently remains high in hypertensive patients despite
      adequate BP control. The factors associated with such phenomena are yet to be
      elucidated. Here, we investigated the factors associated with brachial-ankle PWV
      (baPWV) in 107 patients whose systolic BP was under 140 mmHg at their latest
      baPWV measurement. There were 64 controlled hypertensives and 43 normotensives.
      Multivariate regression analysis identified age, hypertension, body mass index
      (BMI), systolic BP, and heart rate (HR) as independent factors for baPWV. Next,
      we divided the subjects into groups according to their age (in 5-year increments)
      and calculated the mean and standard deviation (SD) of the baPWV for each group.
      For each age group, we defined patients with a baPWV above the mean + SD baPWV
      for the group as the high-baPWV cohort. Multivariate logistic regression analysis
      revealed that BMI, hypertension, and smoking were independent determinants of a
      high-baPWV subject. This represents the first study to report the existence of
      the hypertensive state itself as one of the independent predictors of high baPWV
      in normotensive and well-treated hypertensive patients. This finding implies that
      the hypertensive state itself possibly worsens arterial stiffness independently
      from aging in spite of adequate BP maintenance. To prevent the early progression
      of arterial stiffness, the application of an appropriate intervention during the
      early stages of hypertension is important and the continuation of an appropriate
      BP treatment is suggested.

PMID- 29066907
TI  - Role of the multidisciplinary team in the care of the tracheostomy patient.
AB  - Tracheostomies are used to provide artificial airways for increasingly complex
      patients for a variety of indications. Patients and their families are dependent
      on knowledgeable multidisciplinary staff, including medical, nursing, respiratory
      physiotherapy and speech and language therapy staff, dieticians and
      psychologists, from a wide range of specialty backgrounds. There is increasing
      evidence that coordinated tracheostomy multidisciplinary teams can influence the
      safety and quality of care for patients and their families. This article reviews
      the roles of these team members and highlights the potential for improvements in
      care.

PMID- 29066904
TI  - Review of the clinical applications and technological advances of circulating
      tumor DNA in cancer monitoring.
AB  - Circulating cell-free DNA (cfDNA) released by tumor cells, termed ctDNA, closely
      reflects the heterogeneity of primary cancers and their metastases. As a
      noninvasive, real-time monitoring biomarker, ctDNA is a promising tool for
      detecting driver gene mutations, assessing tumor burden and acquired resistance,
      and early diagnosis. However, isolation and enrichment of cfDNA is a big
      challenge due to the high degree of DNA fragmentation and its relatively low
      abundance in the bloodstream. This review aims to provide insights into the
      recent technological advances in acquisition of optimal quality cfDNA, the use of
      preservatives, isolation methods, processing timelines, and detection techniques.
      It also describes clinical applications of ctDNA in cancer patient management.

PMID- 29066908
TI  - Establishing community-based integrated care for elderly patients through
      interprofessional teamwork: a qualitative analysis.
AB  - BACKGROUND: Working in multidisciplinary teams is indispensable for ensuring high
      quality care for elderly people in Japan's rapidly aging society. However, health
      professionals often experience difficulty collaborating in practice because of
      their different educational backgrounds, ideas, and the roles of each profession.
      In this qualitative descriptive study, we reveal how to build interdisciplinary
      collaboration in multidisciplinary teams. METHODS: Semi-structured interviews
      were conducted with a total of 26 medical professionals, including physicians,
      nurses, public health nurses, medical social workers, and clerical personnel.
      Each participant worked as a team member of community-based integrated care. The
      central topic of the interviews was what the participants needed to establish
      collaboration during the care of elderly residents. Each interview lasted for
      about 60 minutes. All the interviews were recorded, transcribed verbatim, and
      subjected to content analysis. RESULTS: The analysis yielded the following three
      categories concerning the necessary elements of building collaboration: 1) two
      types of meeting configuration; 2) building good communication; and 3) effective
      leadership. The two meetings described in the first category - "community care
      meetings" and "individual care meetings" - were aimed at bringing together the
      disciplines and discussing individual cases, respectively. Building good
      communication referred to the activities that help professionals understand each
      other's ideas and roles within community-based integrated care. Effective
      leadership referred to the presence of two distinctive human resources that could
      coordinate disciplines and move the team forward to achieve goals. CONCLUSION:
      Taken together, our results indicate that these three factors are important for
      establishing collaborative medical teams according to health professionals.
      Regular meetings and good communication facilitated by effective leadership can
      promote collaborative practice and mutual understanding between various
      professions.

PMID- 29066909
TI  - Case report of a KIT-mutated melanoma patient with an excellent response to
      apatinib and temozolomide combination therapy.
AB  - Malignant melanoma is one kind of malignant disease which has high rates of
      mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly
      changing with the development of novel agents in recent decades, such as anti-PD
      1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these
      novel agents are very expensive, not all patients can afford them. Apatinib is a
      novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular
      domain of vascular endothelial growth factor receptor 2 (VEGFR-2) and may also be
      effective on Ret, c-KIT, and c-src. Temozolomide (TMZ) is a second-generation
      alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we
      reported a case of metastatic melanoma with an excellent response to apatinib/TMZ
      combination therapy with progression-free survival for more than one year. This
      patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11,
      suggesting that apatinib may induce clinical response via inhibiting VEGFR and c
      KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of
      advanced melanoma with KIT mutation.

PMID- 29066911
TI  - Polygonatum odoratum lectin promotes BECN1 expression and induces autophagy in
      malignant melanoma by regulation of miR1290.
AB  - Autophagy is not only a survival response to growth-factor or nutrient
      deprivation but also an important mechanism for tumor-cell suicide, including
      melanoma. Polygonatum odoratum lectin (POL) displays apoptosis- and autophagy
      inducing effects in many human tumors. POL also inhibits the growth of melanoma
      cells, but its role and molecular mechanism in malignant melanoma remain unclear.
      In this study, we found that POL suppressed proliferation and induced autophagy
      in melanoma cells. miR1290 was upregulated and inhibited autophagy in melanoma.
      BECN1 is the direct functional effector of miR1290. Furthermore, we found that
      POL promoted BECN1 expression though inhibition of miR1290, thus inducing
      melanoma-cell autophagy. This finding elucidates a new role and mechanism for POL
      in melanoma, and provides a potential antineoplastic agent for melanoma
      treatment.

PMID- 29066910
TI  - CYP19A1 gene polymorphism and colorectal cancer etiology in Saudi population:
      case-control study.
AB  - BACKGROUND: Considerable interest is directed toward the enzyme aromatase
      (CYP19A1) and the development of cancer, due to CYP19A1's role in estrogen
      biosynthesis. Several cancers display excessive intra-tumor accumulation of
      estrogens, and aromatase inhibitors are used for treatment. The CYP19A1 gene
      exhibits polymorphism and mutations that can alter its expression or aromatase
      activity and influence estrogen production. We designed this study to investigate
      the link between CYP19A1 polymorphism and susceptibility to colorectal cancer
      (CRC) development in Saudis. PATIENTS AND METHODS: Blood samples from 100 CRC
      patients and 100 healthy controls were drawn for DNA extractions. Three
      polymorphic sites, rs4774585, rs936308, and rs4775936, were genotyped using
      Taqman genotyping by real-time polymerase chain reaction. Allelic and genotype
      frequencies were calculated and compared in the two groups. RESULTS: All single
      nucleotide polymorphisms (SNPs) were polymorphic in Saudis, and comparison of
      allele frequencies showed several differences when compared to other populations.
      None of the SNPs were associated with the risk of CRC development in Saudis
      (P>0.05). Some gender and location (colon or rectal) differences were observed.
      DISCUSSION: The results of this study highlighted the genetic heterogeneity
      existing between populations in the prevalence of different SNPs and their
      relation to disease state. It showed that, although rs4774585, rs936308, and
      rs4775936 are involved in CRC development in several populations, their role is
      not significant in the etiology of CRC in Saudis; however, some SNPs do increase
      susceptibility or resistance to CRC development as judged from the odds ratio.
      Further large-scale studies are warranted to clarify the role of the CYP19A1
      development in CRC.

PMID- 29066912
TI  - Identification of key pathways and genes with aberrant methylation in prostate
      cancer using bioinformatics analysis.
AB  - Prostate cancer (PCa), a multifocal clinically heterogeneous disease, is the most
      commonly diagnosed non-cutaneous neoplasm in men worldwide. The epigenome of PCa
      is a typical representation of catastrophic model of epigenetic alterations
      during tumorigenesis and its progression. Alterations in methylation patterns in
      tumor suppressors, cell cycle, oncogenes and metabolism-related genes are the
      most commonly observed epigenetic alterations in PCa. In this study, we have
      developed a computational strategy to identify methylated biomarker signature
      panels as potential targets of PCa by screening >160 genes reported to be
      epigenetically dysregulated, and shortlisted 26 differentially methylated genes
      (DMGs) that significantly contribute to oncogenesis. The gene ontology and
      functional enrichment analysis were performed, which showed that identified DMGs
      contribute to cellular and metabolic processes such as cell communication, cell
      cycle, response to drugs, apoptosis and p53 signaling. The top hub genes AR,
      CDH13, CDKN2A, DAPK1, GSTP1, CD44 and RASSF1 identified from protein-protein
      interaction network construction using Search Tool for the Retrieval of
      Interacting Genes contributed to hormonal response, inflammatory response, cell
      cycle, reactive oxygen species activity and receptor kinase activity, which are
      related to hallmarks of cancer as revealed by their functional enrichment
      analysis by Cytoscape. These genes were further scrutinized for CpG islands,
      transcription start sites and positions of methylated cytosines to study their
      methylation profiles. Our analysis revealed high negative correlation values
      between methylation frequencies and gene expressions of the hub genes, namely,
      AR, CDH13, CDKN2A, DAPK1, CD44, GSTP1 and RASSF1, which can be used as potential
      diagnostic biomarkers for PCa.

PMID- 29066913
TI  - The expression of microRNA-324-3p as a tumor suppressor in nasopharyngeal
      carcinoma and its clinical significance.
AB  - OBJECTIVE: This study aimed to determine the expression, clinical significance,
      and possible biologic function of microRNA-324-3p in nasopharyngeal carcinoma
      (NPC) tissues. METHODS: In total, 54 NPC and 35 control tissues were collected.
      The correlation between miR-324-3p expression and the clinicopathologic
      characteristics was analyzed. A dual-luciferase reporter gene assay was employed
      to examine the predicted target gene of miR-324-3p. The miR-324-3p expression
      level in 5-8F cells was determined with quantitative reverse transcription
      polymerase chain reaction following the transfection of miR-324-3p mimics and
      inhibitors. Cell proliferation and the percentage of apoptosis were measured with
      MTT and flow cytometry. Cell invasion ability was assessed by Transwell invasion
      assay. RESULTS: Our results showed that miR-324-3p was downregulated in the NPC
      tissues. The expression level of miR-324-3p in poorly differentiated NPC was
      significantly reduced in comparison with that in well/moderately differentiated
      NPC. The expression level in clinical stages III/IV was lower than that in
      clinical stages I/II. Moreover, the expression level of miR-324-3p was
      significantly lower in NPC patients with lymph node metastasis than that in NPC
      patients without lymph node metastasis. NPC patients with higher levels of miR
      324-3p expression also demonstrated a longer survival time. Predictions from
      bioinformatics indicated the Hedgehog pathway transcription gene GLI3 as the
      target gene of miR-324-3p, and the dual- luciferase reporter assay showed that
      miR-324-3p is directly combined with the 3'-untranslated region of GLI3. The
      overexpression of miR-324-3p suppressed cell proliferation and invasion, and it
      enhanced apoptosis in 5-8F cells. CONCLUSION: miR-324-3p can act as a tumor
      suppressor in NPC cells by the negative regula- tion of GLI3 gene.

PMID- 29066914
TI  - Upregulation of long noncoding RNA LOC440040 promotes tumor progression and
      predicts poor prognosis in patients with prostate cancer.
AB  - BACKGROUND/PURPOSE: Long noncoding RNAs (lncRNAs) play a functional role in the
      initiation and progression of prostate cancer (PCa). This study aimed to
      determine differentially expressed lncRNA through high-throughput sequencing
      technology and investigate its expression, biological function and clinical
      correlation with PCa. MATERIALS AND METHODS: Candidate lncRNAs were identified
      through microarray screening and bioanalysis. The expression of lncRNA LOC440040
      in PCa tissues and cell lines was determined by reverse-transcription polymerase
      chain reaction. The relationship between LOC440040 level and clinicopathological
      characteristics was analyzed by paired t-test or chi-square test, and its
      association with patient prognosis was assessed by the Kaplan-Meier method. The
      effects of LOC440040 on PC-3 and 22RV1 cells were evaluated by Cell Counting Kit
      8 (CCK-8), migration, invasion and colony formation assays. RESULTS: LOC440040
      expression was upregulated in PCa tissues and cell lines. Clinicopathological
      analysis showed that patients with high LOC440040 expression exhibited more
      advanced clinical features and shorter overall survival than those with low
      LOC440040 expression. Multivariate regression analysis revealed that LOC440040
      expression was an independent prognostic factor in patients with PCa. Knockdown
      of LOC440040 inhibited PCa cell proliferation, migration and invasion.
      CONCLUSION: LOC440040 may play an oncogenic role in PCa initiation and
      progression. This lncRNA could be a novel molecular prognostic biomarker and a
      potential therapeutic target for PCa.

PMID- 29066915
TI  - Molecular alterations and clinical prognostic factors for cholangiocarcinoma in
      Thai population.
AB  - This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in
      Thai patients. We identified and reviewed the records of patients who had been
      diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA
      extraction were available in our database. The specimens were explored for EGFR,
      KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples.
      Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in
      74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%,
      12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was
      found. Patients with T790M mutation had a significantly longer overall survival
      (18.84 months) than those with the other types of EGFR mutations (4.08 months;
      hazard ratio [HR]: 0.26, P=0.038) and also had a significantly lower median Ki-67
      (22.5% vs 80%, P=0.025). Furthermore, patients with PIK3CA mutations had a
      significantly longer median progression-free survival (15.87 vs 7.01 months; HR:
      0.46, P=0.043). Strongly positive HER2 expression was found in only 1 patient,
      whereas ALK expression was not found. The presence of EGFR and/or PIK3CA
      mutations implies that targeted drugs may provide a feasible CCC treatment in the
      future.

PMID- 29066916
TI  - Mutation analysis and copy number alterations of KIF23 in non-small-cell lung
      cancer exhibiting KIF23 over-expression.
AB  - KIF23 was recently suggested to be a potential molecular target for the treatment
      of lung cancer. This proposal is based on elevated expression of KIF23 in several
      tumors affecting breast, lung, brain, and liver, and also on the presence of
      KIF23 mutations in melanoma and colorectal cancer. Recently, we identified a
      mutation in the KIF23 gene causing a rare hereditary form of dyserythropoietic
      anemia (CDA III) with predisposition to blood cancer. We suggested that KIF23
      overexpression in tumors might be due to the presence of activating somatic
      mutations, and therefore, mutation screening of the KIF23 in 15 non-small-cell
      lung cancer (NSCLC) cases with elevated expression level of KIF23 was undertaken.
      Eight sequence variants were found in all samples. Furthermore, one variant was
      present in two cases, and one variant was case specific. Nine variants were
      previously reported while one variant lacks frequency information. Nine of ten
      cases available for single nucleotide polymorphism-array analysis demonstrated
      aberrant karyotypes with additional copy of entire chromosome 15. Thus, no
      activating somatic mutations in coding regions of the KIF23 were found.
      Furthermore, no mutations were detected in cell cycle genes homology region in
      KIF23 promoter responsible for p53-dependent repression of KIF23 expression. We
      showed that the elevated level of KIF23 could be due to additional copy of
      chromosome 15 demonstrated in 90% of NSCLC cases analyzed in this study.
      Considering the crucial role of KIF23 in the final step of mitosis, the gene is a
      potential molecular marker, and for better understanding of its role in cancer
      development, more tumors should be analyzed.

PMID- 29066917
TI  - Clinical outcome and toxicity evaluation of simultaneous integrated boost pelvic
      IMRT/VMAT at different dose levels combined with androgen deprivation therapy in
      prostate cancer patients.
AB  - BACKGROUND: The role of dose escalation in patients receiving long-term androgen
      deprivation therapy (ADT) is still a controversial issue. The aim of the current
      study was to evaluate whether dose escalation for >=76-80 Gy had any advantage in
      terms of biochemical disease-free survival (BDFS), distant metastasis-free
      survival (DMFS), or overall survival outcomes over the dose levels from 70 to <76
      Gy. PATIENTS AND METHODS: The study included a cohort of 24 patients classified
      with high- and intermediate-risk localized prostate cancer. All patients received
      ADT, starting at 4-6 months before radiation therapy and continued for a total
      period of 12-24 months in high-risk patients. The treatment plan was given in two
      phases. In the first phase, the nodal planning target volume (PTV) and the
      prostate PTV received 48.6 and 54 Gy, respectively, over 27 fractions. The
      treatment was applied through intensity-modulated radiation therapy or volumetric
      modulated arc therapy with a simultaneous integrated boost technique. RESULTS:
      More than half of the patients were in T3-T4 stage, 79.1% of the patients were in
      the high-risk category, and all patients received ADT. The rate of acute grade II
      gastrointestinal and genitourinary toxicities in all patients were 41.7% and
      62.5%, respectively. The rate of freedom from grade II rectal toxicity at 2 years
      was 89% and 83% for patients treated with dose levels <76 and >=76 Gy,
      respectively. The rate of BDFS at 2 years was 90% and 85% for doses <76 and >=76
      Gy, respectively. The DMFS at 2 years was 100% and 76% for dose levels <76 and
      >=76 Gy, respectively. CONCLUSION: In the current study, there were no
      significant differences in the BDFS and DMFS between patients treated with a dose
      of <76 and >=76 Gy, including elective pelvic lymph nodes irradiation combined
      with ADT.

PMID- 29066918
TI  - Asthma with bronchial hypersecretion: expression of mucins and toll-like
      receptors in sputum and blood.
AB  - : Asthma with bronchial hypersecretion is a type of asthma that is poorly
      studied. Its pathogenesis is not well understood, but is probably related to
      innate impaired immunity, particularly with toll-like receptors (TLRs) and
      secretory mucins (MUC). OBJECTIVES: 1) Define the clinical and inflammatory
      phenotype of asthma with bronchial hypersecretion of mucus. 2) Compare the type
      of mucin present in induced sputum (IS) of patients with and without bronchial
      hypersecretion. 3) Determine the expression of TLRs in IS and blood of asthmatics
      with and without bronchial hypersecretion. MATERIALS AND METHODS: Cross-sectional
      study which included 43 non-smoking asthmatic patients without bronchiectasis, 19
      with bronchiectasis, and 24 without bronchial hypersecretion. All patients
      underwent the following: IS, spirometry, fractional exhaled nitric oxide, prick
      test, total immunoglobulin E (IgE), and blood albumin. Analysis of mucins was
      determined by ELISA and expression of TLR2 and TLR4 by flow cytometry. The level
      of asthma control was determined by the Asthma Control Test (ACT) questionnaire
      and quality of life was assessed by the reduced version of the Asthma Quality of
      Life Questionnaire (mini-AQLQ). RESULTS: Asthmatics with bronchial hypersecretion
      were significantly older (62.6 years vs 48.5 years; p=0.02); had greater severity
      (persistent severe asthma 94.7% vs 29.2%; p=0.000); a higher proportion of nasal
      polyposis (36.8% vs 8.3%; p=0.022); less control of asthma (73.7% vs 8.3%;
      p=0,000); a higher proportion of asthma with negative prick test (68.4% vs 16.6%;
      p=0.001), and lower levels of IgE (113.4 IU/mL vs 448 IU/mL; p=0.007), compared
      with asthmatics without bronchial hypersecretion. Significant differences were
      observed neither in the expression of TLRs 2 and 4 in inflammatory cells of IS or
      peripheral blood, nor in the expression of mucins between both groups.
      CONCLUSION: Asthma patients with bronchial hypersecretion have more severe and
      uncontrolled disease, with poor quality of life as well as a non-allergic
      inflammatory phenotype. Within the mechanisms involving these differences, it
      does not appear that mucins and TLRs play an important role.

PMID- 29066919
TI  - Differentiating vocal cord dysfunction from asthma.
AB  - Vocal cord dysfunction (VCD)-associated symptoms are not rare in pediatric
      patients. Dyspnea, wheezing, stridor, chest pain or tightness and throat
      discomfort are the most commonly encountered symptoms. They may occur either at
      rest or more commonly during exercise in patients with VCD, as well as in
      asthmatic subjects. The phase of respiration (inspiration rather than
      expiration), the location of the wheezing origin, the rapid resolution of
      symptoms, and the timing occurring in relation to exercise, when VCD is exercise
      induced, raise the suspicion of VCD in patients who may have been characterized
      as merely asthmatics and, most importantly, had not responded to the appropriate
      treatment. The gold standard method for the diagnosis of VCD is fiberoptic
      laryngoscopy, which may also identify concomitant laryngeal abnormalities other
      than VCD. However, as VCD is an intermittent phenomenon, the procedure should be
      performed while the patient is symptomatic. For this reason, challenges that
      induce VCD symptoms should be performed, such as exercise tests. Recently, for
      the evaluation of patients with exercise-induced VCD, continuous laryngoscopy
      during exercise (such as treadmill, bicycle ergometer, swimming) was used. A
      definite diagnosis of VCD is of importance, especially for those patients who
      have been erroneously characterized as asthmatics, without adequate response to
      treatment. In these cases, another therapeutic approach is necessary, which will
      depend on whether they suffer solely from VCD or from both conditions.

PMID- 29066920
TI  - Study of the clinical and functional characteristics of asthmatic children with
      obstructive sleep apnea.
AB  - BACKGROUND AND OBJECTIVE: The obstructive sleep apnea (OSA) is a common
      respiratory disorder in children, especially those at preschool and school ages.
      This study aimed to describe the characteristics of asthmatic children with OSA
      and the symptoms for a high risk of OSA. SUBJECTS AND METHODS: It was a
      prospective and descriptive study. The data of asthmatic children including
      medical history, clinical examination, blood tests, spirometry, exhaled nitric
      oxide (NO), and respiratory polygraphy were registered for analyses. RESULTS:
      Eighty-five asthmatic children with a mean age of 9.5 +/- 2.1 years were
      included. The prevalence of OSA was 65.9% (56/85) in study subjects. The
      prevalence of severe OSA in children with moderate asthma was significantly
      higher than intermittent and mild asthma. The percentage of asthmatic children
      with OSA who had snoring, sleep disturbance, and nocturnal sweats was
      significantly higher than that of asthmatic children without OSA (48.2% vs 17.2%,
      71.4% vs 27.5%, and 55.1% vs 31.0%, respectively). The presence of allergic
      rhinitis and snoring was associated significantly with a high probability for the
      presence of OSA. CONCLUSION: Children with asthma have a risk of OSA. Asthmatic
      children with suggested symptoms such as snoring or waking up at night should be
      screened for OSA.

PMID- 29066921
TI  - Prevalence, incidence burden, and clinical impact of healthcare-associated
      infections and antimicrobial resistance: a national prevalent cohort study in
      acute care hospitals in Greece.
AB  - BACKGROUND: Assessing the overall burden of healthcare-associated infections
      (HAIs) is challenging, but imperative in evaluating the cost-effectiveness of
      infection control programs. This study aimed to estimate the point prevalence and
      annual incidence of HAIs in Greece and assess the excess length of stay (LOS) and
      mortality attributable to HAIs, overall and for main infection sites and tracer
      antimicrobial resistance (AMR) phenotypes and pathogens. PATIENTS AND METHODS:
      This prevalent cohort study used a nationally representative cross-section of
      8,247 inpatients in 37 acute care hospitals to record active HAIs of all types at
      baseline and overall LOS and in-hospital mortality up to 90 days following
      hospital admission. HAI incidence was estimated using prevalence-to-incidence
      conversion methods. Excess mortality and LOS were assessed by Cox regression and
      multistate models correcting for confounding and time-dependent biases. RESULTS:
      HAIs were encountered with daily prevalence of 9.1% (95% confidence interval [CI]
      7.8%-10.6%). The estimated annual HAI incidence was 5.2% (95% CI 4.4%-5.3%),
      corresponding to approximately 121,000 (95% CI 103,500-123,700) affected patients
      each year in the country. Ninety-day mortality risk was increased by 80% in
      patients with HAI compared to those without HAI (adjusted hazard ratio 1.8; 95%
      CI 1.3-2.6). Lower respiratory tract infections, bloodstream infections, and
      multiple concurrent HAIs doubled the risk of death, whereas surgical site and
      urinary tract infections were not associated with increased mortality. AMR had
      significant impact on the daily risk of 90-day mortality, which was increased by
      90%-110% in patients infected by carbapenem-resistant gram-negative pathogens.
      HAIs increased LOS for an average of 4.3 (95% CI 2.4-6.2) additional days. Mean
      excess LOS exceeded 20 days in infections caused by major carbapenem-resistant
      gram-negative pathogens. CONCLUSION: HAIs, alongside with increasing AMR, pose
      significant burden to the hospital system. Burden estimates obtained in this
      study will be valuable in future evaluations of infection prevention programs.

PMID- 29066923
TI  - Setting priorities in the health care sector - the case of oral anticoagulants in
      nonvalvular atrial fibrillation in Denmark.
AB  - AIM: Resources devoted to health care are limited, therefore setting priorities
      is required. It differs between countries whether decision-making concerning
      health care technologies focus on broad economic perspectives or whether focus is
      narrow on single budgets ("silo mentality"). The cost perspective as one part of
      the full health economic analysis is important for decision-making. With the case
      of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF),
      the aim is to discuss the implication of the use of different cost perspectives
      for decision-making and priority setting. METHODS: In a cost analysis, the annual
      average total costs of five oral anticoagulants (warfarin and non-vitamin K oral
      anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban]) used in
      daily clinical practice in Denmark for the prevention of stroke in NVAF patients
      are analyzed. This is done in pairwise comparisons between warfarin and each NOAC
      based on five potential cost perspectives, from a "drug cost only" perspective up
      to a "societal" perspective. RESULTS: All comparisons of warfarin and NOACs show
      that the cost perspective based on all relevant costs, ie, total costs
      perspective, is essential for the choice of therapy. Focusing on the
      reimbursement costs of the drugs only, warfarin is the least costly option.
      However, with the aim of therapy to prevent strokes and limit bleedings,
      including the economic impact of this, all NOACs, except rivaroxaban, result in
      slightly lower health care costs compared with warfarin. The same picture was
      found applying the societal perspective. CONCLUSION: Many broad cost
      effectiveness analyses of NOACs exist. However, in countries with budget focus in
      decision-making this information does not apply. The present study's case of oral
      anticoagulants has shown that decision-making should be based on health care or
      societal cost perspectives for optimal use of limited resources. Otherwise, the
      risk is that suboptimal decisions will be likely.

PMID- 29066922
TI  - Epidemiology, patient profile, and health care resource use for hepatitis C in
      Italy.
AB  - OBJECTIVE: The objectives of this study were to estimate the prevalence of
      Hepatitis C among six Italian Local Health Units (LHUs), to describe patient and
      antiviral drug characteristics, and to estimate the health care consumption rates
      and related costs for the management of patients affected by hepatitis C virus
      (HCV) infection by using data from routine clinical practice. METHODS: We
      conducted a retrospective study using administrative databases of six Italian
      LHUs. All patients who had a record related to HCV during the enrollment period
      (July 1, 2009, to December 31, 2014) and who had at least 6 months of data
      available prior to the first HCV record were included. The date of the first
      record related to HCV during the enrollment period was considered as a proxy of
      diagnosis and used as the index date. Patients were followed from the index date
      up to 1 year, death, or exiting the database. Using the overall cohort of HCV
      adult patients as the numerator, we estimated the prevalence of HCV among six
      LHUs. The denominators were obtained from the National Institute of Statistics
      (N=1,665,682). We also evaluated descriptive patient's characteristics and
      treatment patterns, and estimated health care consumption rates and related costs
      for the management of the HCV patients. RESULTS: A total of 7,550 patients were
      analyzed, of whom 57% were male with a mean age of 57.6+/-16.4 years. The
      prevalence of HCV was estimated to be 0.45% (95% confidence interval 0.44-0.46).
      During the follow-up period, 78.6% of HCV patients had received no antiviral
      treatment. The annual health care cost associated with HCV infection was ?6,022.7
      (+/-7,922.6) while the cost specific to HCV care was ?3,154.6 (+/-4,972.0).
      CONCLUSION: Our findings showed that, in the Italian real-world setting, only a
      small proportion of HCV-infected patients received an antiviral treatment.
      Despite the current low prevalence of HCV, the economic impact of such disease
      remains high.

PMID- 29066924
TI  - Predictors of reaching a serum uric acid goal in patients with gout and treated
      with febuxostat.
AB  - PURPOSE: Clinical guidelines recommend febuxostat as first-line pharmacologic
      urate-lowering therapy for patients with gout to achieve a goal serum uric acid
      (sUA) <6 mg/dL; however, little is known about other contributing factors. This
      study identified clinical characteristics of patients treated with febuxostat to
      develop and validate a predictive model for achieving a goal sUA. PATIENTS AND
      METHODS: Patients with Humana Medicare or commercial insurance, diagnosed with
      gout and newly initiated on febuxostat (index date February 1, 2009 - December
      31, 2013), were identified for a retrospective cohort study. Patients were
      followed for 365 days and the first valid sUA test result >=120 days after index
      was retained. A stepwise logistic regression with backward elimination was
      estimated to model sUA goal attainment, and a linear model was estimated to model
      the impact of predictor variables on sUA level. RESULTS: The study sample (n=678)
      was divided into a development (training) dataset (n=453) and a validation
      (holdout) dataset (n=225). In the training sample, patients in the sUA <6 mg/dL
      group were on febuxostat for a longer time, were more adherent, and had a lower
      average base-line sUA level (all p<0.0001) vs patients in the sUA >=6 mg/dL
      group. In the logistic model, febuxostat adherence (odds ratio [OR]=1.03,
      p<0.0001) and baseline sUA level (OR=0.84, p<0.0001) increased the odds of
      attaining sUA <6 mg/dL. In the linear regression model, increase in febuxostat
      adherence (p<0.0001), baseline sUA level (p<0.0001), advanced age (p=0.0021), and
      not having congestive heart failure (p<0.05) were associated with a reduction of
      sUA level. Pre-index allopurinol use was a marginally significant predictor of
      sUA level reduction (p=0.06). CONCLUSIONS: Among febuxostat users diagnosed with
      gout in a real-world setting, adherence to febuxostat and lower baseline sUA
      level were the strongest predictors of attaining sUA goal. These findings may
      help clinicians to identify appropriate patients most likely to benefit from
      febuxostat treatment, and underscore the importance of medication adherence in
      this challenging patient population.

PMID- 29066925
TI  - Estimating the prevalence of generalized and partial lipodystrophy: findings and
      challenges.
AB  - BACKGROUND: Lipodystrophy (LD; non-human immunodeficiency virus [HIV]-associated)
      syndromes are a rare body of disorders for which true prevalence is unknown.
      Prevalence estimates of rare diseases are important to increase awareness and
      financial resources. Current qualitative and quantitative estimates of LD
      prevalence range from ~0.1 to 90 cases/million. We demonstrate an approach to
      quantitatively estimate LD prevalence (all, generalized, and partial) through a
      search of 5 electronic medical record (EMR) databases and 4 literature searches.
      METHODS: EMR and literature searches were conducted from 2012 to 2014. For the
      EMR database searches (Quintiles, IMS LifeLink, General Electric Healthcare, and
      Humedica EMR), LD cases were identified by the International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 272.6 (United
      Kingdom General Practice Research Database used other diagnostic codes to
      identify LD) plus additional LD-associated clinical characteristics (patients
      with HIV or documented HIV treatment were excluded). Expert adjudication of cases
      was used for the Quintiles database only. Literature searches (PubMed and EMBASE)
      were conducted for each of the 4 major LD subtypes. Prevalence estimates were
      determined by extrapolating the total number of cases identified for each search
      to the database population (EMR search) and European population (literature
      search). RESULTS: The prevalence range of all LD across all EMR databases was 1.3
      4.7 cases/million. For the adjudicated Quintiles search, the estimated prevalence
      of diagnosed LD was 3.07 cases/million (95% confidence interval [CI], 2.30-4.02),
      0.23 cases/million (95% CI, 0.06-0.59) and 2.84 cases/million (95% CI, 2.10-3.75)
      for generalized lipodystrophy (GL) and partial lipodystrophy (PL), respectively.
      For all literature searches, the prevalence of all LD in Europe was 2.63
      cases/million (0.96 and 1.67 cases/million for GL and PL, respectively).
      CONCLUSION: LD prevalence estimates are at the lower range of previously
      established numbers, confirming that LD is an ultra-rare disease. The
      establishment of diagnostic criteria and coding specific to the 4 major LD
      subtypes and future studies/patient registries are needed to further refine our
      estimates.

PMID- 29066927
TI  - Career planning and mentorship: a few key considerations for trainees.
AB  - Publishing and securing funding are considered our "academic currency", and
      therefore, both should be emphasized during training, both residency and
      fellowship. Trainees should make an effort to find funding opportunities at or
      outside of their institutions and try to identify their short- and long-term
      goals. Establishing a track record of publications can help trainees get hired,
      funded, and promoted as junior faculty, and effective networking and mentorship
      are critical determinants of academic success. Given the positive effects of
      mentorship, trainees should understand what comprises a good mentor-mentee
      relationship and how to optimize the mentoring process. The objective of this
      article is to discuss few key considerations for trainees in residency or
      fellowship regarding mentorship and career planning in academic medicine.

PMID- 29066926
TI  - Awareness of diabetic retinopathy among patients with type 2 diabetes mellitus in
      Jordan.
AB  - BACKGROUND: Increasing the level of awareness of diabetic retinopathy among
      individuals with type 2 diabetes mellitus is considered an important factor for
      early diagnosis and management of diabetic retinopathy. The aim of this study was
      to evaluate awareness of diabetic retinopathy among a sample of type 2 diabetes
      mellitus patients in Jordan. PATIENTS AND METHODS: The study period was from
      August to December 2015. The sample was selected randomly from patients with type
      2 diabetes mellitus from the general population in three main cities of Jordan
      (Amman, Irbid, and Zarqa). A questionnaire was distributed to 237 participants
      with diabetes to assess their awareness and knowledge of diabetes and diabetic
      retinopathy. The questionnaire included questions to assess awareness about
      diabetic retinopathy, sources of knowledge about the disease, and patients'
      knowledge and compliance with available treatments and routine eye examinations.
      Patients were also questioned about the barriers that may interfere with early
      eye examination. RESULTS: A total of 237 participants (107 [45.1%] females and
      130 [54.9%] males) with type 2 diabetes were interviewed. Mean age+/-SD for the
      study population was 54.51+/-10.28 years. Of the study population, 88.2% were
      aware that diabetes can affect the eyes and 81% reported that diabetic
      retinopathy can lead to blindness. Higher level of patients' awareness of
      diabetic retinopathy was related to higher level of formal education (p<0.05).
      The main source of information about diabetic retinopathy as reported by 47.3%
      patients was general practitioners. Patients' compliance with diabetes management
      was relatively high; however, their compliance with routine retinal assessment
      was poor, with only a total of 29.5% of participants having had an eye
      examination in the previous year. CONCLUSION: Awareness of the nature and
      consequences of diabetic retinopathy among patients with diabetes in Jordan is
      relatively high. However, patients' motivation to undergo retinal assessment was
      poor in the sample, thus hindering early diagnosis and management.

PMID- 29066928
TI  - Assessment and treatment of breakthrough cancer pain: from theory to clinical
      practice.
AB  - Breakthrough cancer pain (BTcP) is a common condition in oncological patients.
      However, its management is still suboptimal. Improved knowledge of BTcP and its
      management in clinical practice may have immediate importance for all physicians
      involved in the supportive care of cancer patients. This review critically
      discusses the most important concepts for the correct diagnosis of BTcP and
      presents some intriguing cases of the management of this condition in clinical
      practice. Overall, the most appropriate therapeutic choice appears to be a rapid
      onset opioid (ROO), and in particular, the nasal route of administration is the
      quickest and most convenient mode of administration for the management of BTcP,
      especially when the patient needs rapid resolution of pain. To this end,
      intranasal fentanyl spray may have a particular relevance in clinical practice.
      Future research should focus on accepted definitions of BTcP to investigate the
      optimal management of this highly heterogeneous pain condition. Therapeutic
      decision-making of patients, clinicians, and payers will likely be driven from
      results of well-designed clinical trials of ROOs.

PMID- 29066929
TI  - Experimental and procedural pain responses in primary dysmenorrhea: a systematic
      review.
AB  - Primary dysmenorrhea (PD) has been the focus of a number of experimental pain
      studies. Although a number of reviews exist, few have critically evaluated the
      existing body of research on PD and experimental and procedural pain. Data from
      19 published research articles that include women with PD and responses to an
      experimental or procedural pain stimulus (or stimuli) suggest that women with PD
      may have elevated pain reactivity, as compared to women without PD. This pattern
      appears to be true across different phases of the menstrual cycle. However, there
      is an abundance of conflicting findings, which may be due to significant
      methodological issues such as inconsistent definitions of PD, wide variation in
      experimental pain methodologies, and inaccurate assessment of the menstrual
      cycle. Future research should focus on identifying specific symptoms (i.e., pain
      threshold ratings) to more clearly define what constitutes PD, establish reliable
      and valid laboratory testing protocols, and assess the menstrual cycle with
      greater precision.

PMID- 29066930
TI  - The effect of pregabalin or duloxetine on arthritis pain: a clinical and
      mechanistic study in people with hand osteoarthritis.
AB  - Osteoarthritis (OA) is the most prevalent arthritis worldwide and is
      characterized by chronic pain and impaired physical function. We hypothesized
      that heightened pain in hand OA could be reduced with duloxetine or pregabalin.
      In this prospective, randomized clinical study, we recruited 65 participants,
      aged 40-75 years, with a Numerical Rating Scale (NRS) for pain of at least 5.
      Participants were randomized to one of the following three groups: duloxetine,
      pregabalin, and placebo. The primary endpoint was the NRS pain score, and the
      secondary endpoints included the Australian and Canadian Hand Osteoarthritis
      Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory
      testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA
      found significant differences between the three groups (P=0.0078). In the
      intention-to-treat analysis, the pregabalin group showed improvement for NRS pain
      (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no
      difference between duloxetine and placebo (P>0.05) was observed. In the per
      protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine
      (P=0.029) compared to placebo. We conclude that centrally acting analgesics
      improve pain outcomes in people with hand arthritis, offering new treatment
      paradigms for OA pain.

PMID- 29066931
TI  - The safety profile of parecoxib for the treatment of postoperative pain: a pooled
      analysis of 28 randomized, double-blind, placebo-controlled clinical trials and a
      review of over 10 years of postauthorization data.
AB  - BACKGROUND: Nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) and
      selective cyclooxygenase-2 (COX-2) inhibitors are associated with safety issues
      including cardiovascular, renal, and gastrointestinal (GI) events. OBJECTIVE: To
      examine the safety of parecoxib, a COX-2 inhibitor, for the management of
      postoperative pain. DESIGN: Pooled analysis of 28 placebo-controlled trials of
      parecoxib and review of postauthorization safety data. MAIN OUTCOME MEASURES:
      Prespecified safety events commonly associated with COX-2 inhibitors and/or
      NSAIDs. In the clinical trial analysis, the frequency of each event was compared
      between treatment groups using a chi-square test. In the postauthorization
      review, the number of confirmed cases, along with outcome, was presented for each
      event. RESULTS: In the clinical trial analysis, GI-related events occurred in
      ~0.2% of patients in the parecoxib and placebo groups. Renal failure and
      impairment was similar between parecoxib (1.0%) and placebo (0.9%). The
      occurrence of arterial (parecoxib=0.3%; placebo=0.2%) and venous (parecoxib=0.2%;
      placebo=0.1%) cardiovascular embolic and thrombotic events was similar between
      groups. Hypersensitivity reactions including anaphylactic reactions
      (parecoxib=8.7%; placebo=8.6%), hypotension (parecoxib=2.6%; placebo=2.1%),
      angioedema (parecoxib=2.5%; placebo=2.8%), and severe cutaneous adverse reactions
      (0% in both groups) were similar between groups. Incision site or other
      skin/tissue infections occurred in <0.1% of patients in both groups. The
      occurrence of these events (total reports/serious reports) in the
      postauthorization database, based on 69,567,300 units of parecoxib, was as
      follows: GI ulceration-related events (35/35), renal failure and impairment
      (77/68), cardiovascular embolic and thrombotic events (66/64), hypersensitivity
      reactions including hypotension-related events (32/25) and severe cutaneous
      adverse events (17/17), and masking signs of inflammation (18/18). A majority of
      reported outcomes were classified as recovered or recovering. CONCLUSIONS:
      Potentially serious safety events occur infrequently with parecoxib, which high
      lights its safety in patients with postoperative pain.

PMID- 29066932
TI  - Efficiency of spinal anesthesia versus general anesthesia for lumbar spinal
      surgery: a retrospective analysis of 544 patients.
AB  - BACKGROUND: Previous studies have shown varying results in selected outcomes when
      directly comparing spinal anesthesia to general in lumbar surgery. Some studies
      have shown reduced surgical time, postoperative pain, time in the postanesthesia
      care unit (PACU), incidence of urinary retention, postoperative nausea, and more
      favorable cost-effectiveness with spinal anesthesia. Despite these results, the
      current literature has also shown contradictory results in between-group
      comparisons. MATERIALS AND METHODS: A retrospective analysis was performed by
      querying the electronic medical record database for surgeries performed by a
      single surgeon between 2007 and 2011 using procedural codes 63030 for diskectomy
      and 63047 for laminectomy: 544 lumbar laminectomy and diskectomy surgeries were
      identified, with 183 undergoing general anesthesia and 361 undergoing spinal
      anesthesia (SA). Linear and multivariate regression analyses were performed to
      identify differences in blood loss, operative time, time from entering the
      operating room (OR) until incision, time from bandage placement to exiting the
      OR, total anesthesia time, PACU time, and total hospital stay. Secondary outcomes
      of interest included incidence of postoperative spinal hematoma and death,
      incidence of paraparesis, plegia, post-dural puncture headache, and paresthesia,
      among the SA patients. RESULTS: SA was associated with significantly lower
      operative time, blood loss, total anesthesia time, time from entering the OR
      until incision, time from bandage placement until exiting the OR, and total
      duration of hospital stay, but a longer stay in the PACU. The SA group
      experienced one spinal hematoma, which was evacuated without any long-term
      neurological deficits, and neither group experienced a death. The SA group had no
      episodes of paraparesis or plegia, post-dural puncture headaches, or episodes of
      persistent postoperative paresthesia or weakness. CONCLUSION: SA is effective for
      use in patients undergoing elective lumbar laminectomy and/or diskectomy spinal
      surgery, and was shown to be the more expedient anesthetic choice in the
      perioperative setting.

PMID- 29066933
TI  - Healthy lifestyle behavior and risk of long duration troublesome neck pain or low
      back pain among men and women: results from the Stockholm Public Health Cohort.
AB  - BACKGROUND: The role of healthy lifestyle behavior (HLB) in terms of physical
      activity, alcohol intake, smoking, and diet put together has not yet been
      explored for the risk of low back pain (LBP) and neck pain (NP). Our aim was to
      study if an HLB is protective against the onset of long duration troublesome LBP
      and NP in men and women. METHODS: Two cohorts from the Stockholm Public Health
      Cohort, free from LBP (n=12,483) and NP (n=10,539), respectively, in 2006, were
      surveyed with questionnaires. Baseline information about physical activity,
      alcohol intake, diet, and smoking were dichotomized into being healthy/not
      healthy and combined in a categorical variable according to the number of healthy
      behaviors present. Binomial regression analyses were used to evaluate the role of
      HLB for the outcomes 4 years later. RESULTS: When men with three or four healthy
      lifestyles were compared to men with none or one, the risk ratio (RR) of LBP was
      0.63 (95% confidence interval [CI]: 0.39-1.02). The corresponding RR for LBP in
      women was 0.86 (95% CI: 0.56-1.32). When men with three or four healthy
      lifestyles were compared to men with none or one, the RR for NP was 1.13 (95% CI:
      0.74-1.71). The corresponding RR for NP in women was 0.52 (95% CI: 0.35-0.77).
      CONCLUSION: An HLB seems to be protective for long duration troublesome LBP in
      men, and for long duration troublesome NP in women.

PMID- 29066934
TI  - Adolescent girls and young women living with HIV: preconception counseling
      strategies.
AB  - BACKGROUND: Rates of pregnancy among women living with HIV are similar to those
      in the general population. Unintended pregnancies are also common, and among
      adolescents and young women perinatally infected (PHIV+) or behaviorally infected
      (BHIV+) with HIV, planning for both conception and contraception is an important
      element of HIV care that may be neglected. This pilot study examined the
      influence of intervention strategies targeting fertility planning, safer
      conception practices and patient-provider communication. It was hypothesized that
      preconception counseling interventions would enhance reproductive knowledge,
      planning and practices, as well as stimulate discussion with providers regarding
      conception. METHODS: Adolescent girls and young women (N=34) perinatally (n=21)
      or behaviorally (n=13) infected with HIV, aged 16-29 years, were recruited from
      urban South Florida, and completed measures of reproductive knowledge, sexual
      practices and fertility intentions. Participants were randomized to condition,
      ie, video presentation plus Motivational Interviewing (MI), MI only, control.
      RESULTS: The average age of women was 22 years (SD =3.27), and the majority of
      them were African American. Levels of depression were higher among BHIV+ compared
      to PHIV+ at baseline and 6 months. Pregnancy knowledge (pregnancy, safe
      conception and pregnancy planning) and the proportion of those engaging in birth
      control planning (condom use, long-term birth control, patient-provider
      discussions on preventing pregnancy and fertility desires) were similar between
      conditions at post-intervention and 6 months. Bayes factors indicated that the
      data were insensitive with regard to differences between conditions, limiting
      support for both the null and alternative hypotheses. CONCLUSION: The impact of
      interventions used in this study to stimulate pregnancy planning was
      inconclusive. Results suggest that pregnancy planning interventions may require
      greater intensity to influence sexual behavior in this population. Despite
      adequate reproductive knowledge, HIV-infected adolescent girls and young women
      may fail to engage in planning behavior.

PMID- 29066935
TI  - Female sexual dysfunction: a focus on flibanserin.
AB  - Flibanserin is the first US Food and Drug Administration (FDA)-approved option
      for sexual dysfunction, specifically low sexual desire. Until recently, there
      were no FDA-approved medication options to assist the ~40% of women affected by
      female sexual dysfunction (FSD). Often, patients report feeling uncomfortable
      discussing sexual health, identifying a strong need for health care professionals
      (HCPs) to proactively reach out to patients to identify concerns and initiate a
      discussion about sexual health and the available treatment options. Within the
      Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DMS-5), the
      criteria of female sexual interest/arousal disorder (FSIAD) are outlined,
      encompassing one of the most common sexual concerns, formerly in its own category
      defined as hypoactive sexual desire disorder (HSDD) or low sexual desire. HSDD is
      the absence or deficiency of sexual interest and/or desire leading to significant
      distress and interpersonal difficulties. HCPs offer an important service in
      assessing their patients and providing information about treatment considerations
      while ensuring patient comfort with this topic. This article provides an overview
      of the types and potential causes associated with FSD and the role of flibanserin
      in practice as a treatment option. Despite a need for additional study in diverse
      populations, flibanserin has demonstrated efficacy with increased female sexual
      function index (FSFI) total and desire domain scores in clinical studies
      indicating benefit in sexual desire. Common patient or provider-administered
      assessment tools to assist in identifying affected patients and patient
      counseling strategies are reviewed.

PMID- 29066936
TI  - Automated external defibrillation training on the left or the right side - a
      randomized simulation study.
AB  - BACKGROUND: Correct placement of the left automated external defibrillator (AED)
      electrode is rarely achieved. AED electrode placement is predominantly
      illustrated and trained with the rescuer sitting on the right side of the
      patient. Placement of the AED electrodes from the left side of the patient may
      result in a better overview of and access to the left lateral side of the thorax.
      This study aimed to investigate if training in automated external defibrillation
      on the left side compared to the right side of a manikin improves left AED
      electrode placement. METHODS: Laypeople attending basic life support training
      were randomized to learn automated external defibrillation from the left or right
      side of a manikin. After course completion, participants used an AED and placed
      AED electrodes in a simulated cardiac arrest scenario. RESULTS: In total, 40
      laypersons were randomized to AED training on the left (n=19 [missing data =1],
      63% female, mean age: 47.3 years) and right (n=20, 75% female, mean age: 48.7
      years) sides of a manikin. There was no difference in left AED electrode
      placement when trained on the left or right side: the mean (SD) distances to the
      recommended left AED electrode position were 5.9 (2.1) cm vs 6.9 (2.2) cm
      (p=0.15) and to the recommended right AED electrode position were 2.6 (1.5) cm vs
      1.8 (0.8) cm (p=0.06), respectively. CONCLUSION: Training in automated external
      defibrillation on the left side of a manikin does not improve left AED electrode
      placement compared to training on the right side.

PMID- 29066937
TI  - Empirical research on the utility of a preparation manual for a disaster medical
      response drill.
AB  - PURPOSE: It is difficult for emergency physicians to plan and execute a disaster
      medical response drill while conducting their daily work activities. Readily
      available drill preparation manuals are therefore essential, alongside assessment
      methods to ensure quality. Here, we propose email text analysis as a manual
      assessment method, and investigate its validity. METHODS: The preparation status
      of two similar large-scale disaster medical response drills were compared. All
      email texts exchanged during the preparation stage were analyzed, and frequently
      appearing words (quality element) and word counts (quantity element) were
      compared between Drill 1, which was organized without a manual, and Drill 2,
      organized with a manual. RESULTS: Word frequency analysis revealed that the key
      components of the manual (visualization of necessary work, preparation of
      documents in a certain format, and clarification of aims of the drill)
      contributed to the effectiveness of the preparation process for Drill 2.
      Furthermore, work volume during the preparation for Drill 2 was decreased by
      41.9% from that during the preparation for Drill 1. CONCLUSION: Preparation of a
      high-quality manual is crucial so that emergency physicians can plan and execute
      a disaster medical response drill. Email text analysis can serve as an objective
      method assessing the quality of manuals.

PMID- 29066938
TI  - Prognostic value of soluble major histocompatibility complex class I polypeptide
      related sequence A in non-small-cell lung cancer - significance and development.
AB  - Soluble major histocompatibility complex class I polypeptide-related sequence A
      (sMICA) is a useful marker in surveillance of lung cancer. High serum sMICA level
      in patients with non-small-cell lung cancer (NSCLC) seems to be a poor prognostic
      factor being correlated with poor differentiation and advanced stage. However,
      the low specificity limits its role as a single prognostic marker of NSCLC, but
      its evaluation, in addition to standard serum markers, could improve the staging
      of NSCLC. Despite promising, all current studies are insufficient to assess the
      real efficiency of sMICA as a prognostic marker of NSCLC, and hence, future
      studies are required to validate it.

PMID- 29066939
TI  - Prevalence of neuro-musculoskeletal pain and dysfunction in open-heart surgical
      patients preoperatively and at 6 and 12 weeks postoperatively: a prospective
      longitudinal observation study.
AB  - Chronic neuro-musculoskeletal pain is an important complication of open-heart
      surgery (OHS). To better understand the development and natural course of neuro
      musculoskeletal pain in the immediate post-OHS period, this prospective
      longitudinal study assessed the prevalence and degree of pain and shoulder
      disability, and areas of pain pre- and post-OHS. Usual medical, nursing, and
      physiotherapy care was provided including early extubation, education, walking,
      sitting out of bed, and upper, lower limb, and trunk exercises from day 1 post
      operation. Of 114 elective patients who provided consent, 98 subjects were
      surveyed preoperatively, and at week 6 and week 12 post-OHS. Open and closed
      questions encompassed numerical rating of pain scales for various body areas
      summed as a total pain score (TPS), the shoulder disability score (SDS), exercise
      compliance, and sternal clicking. Usual care comprised mobility exercises,
      walking program, and cardiac rehabilitation referral. Survey return rates were
      100%, 88%, and 82%, respectively. Of the 76 (78%) subjects with complete data
      sets, 68% subjects reported a history of previous neuro-musculoskeletal
      injuries/conditions preoperatively while prevalence for neuro-musculoskeletal
      pain was 64%, 88%, and 67% and 38%, 63%, and 42% for shoulder disability, at the
      three assessments. In all, 11% subjects reported sternal clicking at week 6 and
      7% at week 12. Pain commonly occurred in the lower back and neck preoperatively,
      and in front of the chest, neck, rib cage, upper back, and left shoulder at week
      6. Rib cage pain alone remained significantly greater than preoperative levels by
      week 12 post-OHS. Preoperative SDS was positively correlated with post-OHS length
      of stay; women had higher SDSs than men at week 6 and week 12 and week 12 SDS was
      negatively correlated with height. Surgical risk score was negatively correlated
      with change in SDS and TPS from pre-operation to week 12. In conclusion, neuro
      musculoskeletal pain and shoulder disability were common preoperatively and while
      prevalence increased at week 6 post-OHS, overall preoperative levels were
      restored by week 12.

PMID- 29066941
TI  - Performance Enzymes for Food Ingredients at the BIO World Congress-Enabling
      Biotechnologies and Supporting Capabilities Join in a Model for Successful
      Commercialization of Food Ingredients.

PMID- 29066942
TI  - Training Deep Convolutional Neural Networks with Resistive Cross-Point Devices.
AB  - In a previous work we have detailed the requirements for obtaining maximal deep
      learning performance benefit by implementing fully connected deep neural networks
      (DNN) in the form of arrays of resistive devices. Here we extend the concept of
      Resistive Processing Unit (RPU) devices to convolutional neural networks (CNNs).
      We show how to map the convolutional layers to fully connected RPU arrays such
      that the parallelism of the hardware can be fully utilized in all three cycles of
      the backpropagation algorithm. We find that the noise and bound limitations
      imposed by the analog nature of the computations performed on the arrays
      significantly affect the training accuracy of the CNNs. Noise and bound
      management techniques are presented that mitigate these problems without
      introducing any additional complexity in the analog circuits and that can be
      addressed by the digital circuits. In addition, we discuss digitally programmable
      update management and device variability reduction techniques that can be used
      selectively for some of the layers in a CNN. We show that a combination of all
      those techniques enables a successful application of the RPU concept for training
      CNNs. The techniques discussed here are more general and can be applied beyond
      CNN architectures and therefore enables applicability of the RPU approach to a
      large class of neural network architectures.

PMID- 29066940
TI  - Intranasal naloxone and related strategies for opioid overdose intervention by
      nonmedical personnel: a review.
AB  - Deaths due to prescription and illicit opioid overdose have been rising at an
      alarming rate, particularly in the USA. Although naloxone injection is a safe and
      effective treatment for opioid overdose, it is frequently unavailable in a timely
      manner due to legal and practical restrictions on its use by laypeople. As a
      result, an effort spanning decades has resulted in the development of strategies
      to make naloxone available for layperson or "take-home" use. This has included
      the development of naloxone formulations that are easier to administer for
      nonmedical users, such as intranasal and autoinjector intramuscular delivery
      systems, efforts to distribute naloxone to potentially high-impact categories of
      nonmedical users, as well as efforts to reduce regulatory barriers to more
      widespread distribution and use. Here we review the historical and current
      literature on the efficacy and safety of naloxone for use by nonmedical persons,
      provide an evidence-based discussion of the controversies regarding the safety
      and efficacy of different formulations of take-home naloxone, and assess the
      status of current efforts to increase its public distribution. Take-home naloxone
      is safe and effective for the treatment of opioid overdose when administered by
      laypeople in a community setting, shortening the time to reversal of opioid
      toxicity and reducing opioid-related deaths. Complementary strategies have
      together shown promise for increased dissemination of take-home naloxone,
      including 1) provision of education and training; 2) distribution to critical
      populations such as persons with opioid addiction, family members, and first
      responders; 3) reduction of prescribing barriers to access; and 4) reduction of
      legal recrimination fears as barriers to use. Although there has been
      considerable progress in decreasing the regulatory and legal barriers to
      effective implementation of community naloxone programs, significant barriers
      still exist, and much work remains to be done to integrate these programs into
      efforts to provide effective treatment of opioid use disorders.

PMID- 29066943
TI  - Optimization of trans-Splicing for Huntington's Disease RNA Therapy.
AB  - Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a
      polyglutamine (polyQ) expansion in exon 1 of the Huntingtin (HTT) gene. We have
      previously demonstrated that spliceosome-mediated trans-splicing is a viable
      molecular strategy to specifically reduce and repair mutant HTT (mtHTT). Here,
      the targeted tethering efficacy of the pre-mRNA trans-splicing modules (PTM) in
      HTT was optimized. Various PTMs that targeted the 3' end of HTT intron 1 or the
      intron 1 branch point were shown trans-splice into an HTT mini-gene, as well as
      the endogenous HTT pre-mRNA. PTMs that specifically target the endogenous intron
      1 branch point increased the trans-splicing efficacy from 1-5 to 10-15%.
      Furthermore, lentiviral expression of PTMs in a human HD patient iPSC-derived
      neural culture significantly reversed two previously established polyQ-length
      dependent phenotypes. These results suggest that pre-mRNA repair of mtHTT could
      hold therapeutic benefit and it demonstrates an alternative platform to correct
      the mRNA product produced by the mtHTT allele in the context of HD.

PMID- 29066946
TI  - Novel Stimulation Paradigms with Temporally-Varying Parameters to Reduce
      Synchronous Activity at the Onset of High Frequency Stimulation in Rat
      Hippocampus.
AB  - Deep brain stimulation (DBS) has shown wide applications for treating various
      disorders in the central nervous system by using high frequency stimulation (HFS)
      sequences of electrical pulses. However, upon the onset of HFS sequences, the
      narrow pulses could induce synchronous firing of action potentials among large
      populations of neurons and cause a transient phase of "onset response" that is
      different from the subsequent steady state. To investigate the transient onset
      phase, the antidromically-evoked population spikes (APS) were used as an
      electrophysiological marker to evaluate the synchronous neuronal reactions to
      axonal HFS in the hippocampal CA1 region of anesthetized rats. New stimulation
      paradigms with time-varying intensity and frequency were developed to suppress
      the "onset responses". Results show that HFS paradigms with ramp-up intensity at
      the onset phase could suppress large APS potentials. In addition, an intensity
      ramp with a slower ramp-up rate or with a higher pulse frequency had greater
      suppression on APS amplitudes. Therefore, to reach a desired pulse intensity
      rapidly, a stimulation paradigm combining elevated frequency and ramp-up
      intensity was used to shorten the transition phase of initial HFS without evoking
      large APS potentials. The results of the study provide important clues for
      certain transient side effects of DBS and for development of new adaptive
      stimulation paradigms.

PMID- 29066944
TI  - A Polymer Physics Investigation of the Architecture of the Murine Orthologue of
      the 7q11.23 Human Locus.
AB  - In the last decade, the developments of novel technologies, such as Hi-C or GAM
      methods, allowed to discover that chromosomes in the nucleus of mammalian cells
      have a complex spatial organization, encompassing the functional contacts between
      genes and regulators. In this work, we review recent progresses in chromosome
      modeling based on polymer physics to understand chromatin structure and folding
      mechanisms. As an example, we derive in mouse embryonic stem cells the full 3D
      structure of the Bmp7 locus, a genomic region that plays a key role in
      osteoblastic differentiation. Next, as an application to Neuroscience, we present
      the first 3D model for the mouse orthologoue of the Williams-Beuren syndrome
      7q11.23 human locus. Deletions and duplications of the 7q11.23 region generate
      neurodevelopmental disorders with multi-system involvement and variable
      expressivity, and with autism. Understanding the impact of such mutations on the
      rewiring of the interactions of genes and regulators could be a new key to make
      sense of their related diseases, with potential applications in biomedicine.

PMID- 29066945
TI  - Effect of EEG Referencing Methods on Auditory Mismatch Negativity.
AB  - Auditory event-related potentials (ERPs) have consistently been used in the
      investigation of auditory and cognitive processing in the research and clinical
      laboratories. There is currently no consensus on the choice of appropriate
      reference for auditory ERPs. The most commonly used references in auditory ERP
      research are the mathematically linked-mastoids (LM) and average referencing
      (AVG). Since LM and AVG referencing procedures do not solve the issue of
      electrically-neutral reference, Reference Electrode Standardization Technique
      (REST) was developed to create a neutral reference for EEG recordings. The aim of
      the current research is to compare the influence of the reference on amplitude
      and latency of auditory mismatch negativity (MMN) as a function of magnitude of
      frequency deviance across three commonly used electrode montages (16, 32, and 64
      channel) using REST, LM, and AVG reference procedures. The current study was
      designed to determine if the three reference methods capture the variation in
      amplitude and latency of MMN with the deviance magnitude. We recorded MMN from 12
      normal hearing young adults in an auditory oddball paradigm with 1,000 Hz pure
      tone as standard and 1,030, 1,100, and 1,200 Hz as small, medium and large
      frequency deviants, respectively. The EEG data recorded to these sounds was re
      referenced using REST, LM, and AVG methods across 16-, 32-, and 64-channel EEG
      electrode montages. Results revealed that while the latency of MMN decreased with
      increment in frequency of deviant sounds, no effect of frequency deviance was
      present for amplitude of MMN. There was no effect of referencing procedure on the
      experimental effect tested. The amplitude of MMN was largest when the ERP was
      computed using LM referencing and the REST referencing produced the largest
      amplitude of MMN for 64-channel montage. There was no effect of electrode-montage
      on AVG referencing induced ERPs. Contrary to our predictions, the results suggest
      that the auditory MMN elicited as a function of increments in frequency deviance
      does not depend on the choice of referencing procedure. The results also suggest
      that auditory ERPs generated using REST referencing is contingent on the
      electrode arrays more than the AVG referencing.

PMID- 29066948
TI  - Is Arc mRNA Unique: A Search for mRNAs That Localize to the Distal Dendrites of
      Dentate Gyrus Granule Cells Following Neural Activity.
AB  - There have been several attempts to identify which RNAs are localized to
      dendrites; however, no study has determined which RNAs localize to the dendrites
      following the induction of synaptic activity. We sought to identify all RNA
      transcripts that localize to the distal dendrites of dentate gyrus granule cells
      following unilateral high frequency stimulation of the perforant pathway (pp-HFS)
      using Sprague Dawley rats. We then utilized laser microdissection (LMD) to very
      accurately dissect out the distal 2/3rds of the molecular layer (ML), which
      contains these dendrites, without contamination from the granule cell layer, 2
      and 4 h post pp-HFS. Next, we purified and amplified RNA from the ML and
      performed an unbiased screen for 27,000 RNA transcripts using Affymetrix
      microarrays. We determined that Activity Regulated Cytoskeletal Protein
      (Arc/Arg3.1) mRNA, exhibited the greatest fold increase in the ML at both
      timepoints (2 and 4 h). In total, we identified 31 transcripts that increased
      their levels within the ML following pp-HFS across the two timepoints. Of
      particular interest is that one of these identified transcripts was an
      unprocessed micro-RNA (pri-miR132). Fluorescent in situ hybridization and qRT-PCR
      were used to confirm some of these candidate transcripts. Our data indicate Arc
      is a unique activity dependent gene, due to the magnitude that its activity
      dependent transcript localizes to the dendrites. Our study determined other
      activity dependent transcripts likely localize to the dendrites following neural
      activity, but do so with lower efficiency compared to Arc.

PMID- 29066950
TI  - Sphingosine-1-Phosphate and the S1P3 Receptor Initiate Neuronal Retraction via
      RhoA/ROCK Associated with CRMP2 Phosphorylation.
AB  - The bioactive lipid sphingosine-1-phosphate (S1P) is an important regulator in
      the nervous system. Here, we explored the role of S1P and its receptors in vitro
      and in preclinical models of peripheral nerve regeneration. Adult sensory neurons
      and motor neuron-like cells were exposed to S1P in an in vitro assay, and
      virtually all neurons responded with a rapid retraction of neurites and growth
      cone collapse which were associated with RhoA and ROCK activation. The S1P1
      receptor agonist SEW2871 neither activated RhoA or neurite retraction, nor was
      S1P-induced neurite retraction mitigated in S1P1-deficient neurons. Depletion of
      S1P3 receptors however resulted in a dramatic inhibition of S1P-induced neurite
      retraction and was on the contrary associated with a significant elongation of
      neuronal processes in response to S1P. Opposing responses to S1P could be
      observed in the same neuron population, where S1P could activate S1P1 receptors
      to stimulate elongation or S1P3 receptors and retraction. S1P was, for the first
      time in sensory neurons, linked to the phosphorylation of collapsin response
      mediated protein-2 (CRMP2), which was inhibited by ROCK inhibition. The improved
      sensory recovery after crush injury further supported the relevance of a critical
      role for S1P and receptors in fine-tuning axonal outgrowth in peripheral neurons.

PMID- 29066949
TI  - Regulation of Exocytotic Fusion Pores by SNARE Protein Transmembrane Domains.
AB  - Calcium-triggered exocytotic release of neurotransmitters and hormones from
      neurons and neuroendocrine cells underlies neuronal communication, motor activity
      and endocrine functions. The core of the neuronal exocytotic machinery is
      composed of soluble N-ethyl maleimide sensitive factor attachment protein
      receptors (SNAREs). Formation of complexes between vesicle-attached v- and plasma
      membrane anchored t-SNAREs in a highly regulated fashion brings the membranes
      into close apposition. Small, soluble proteins called Complexins (Cpx) and
      calcium-sensing Synaptotagmins cooperate to block fusion at low resting calcium
      concentrations, but trigger release upon calcium increase. A growing body of
      evidence suggests that the transmembrane domains (TMDs) of SNARE proteins play
      important roles in regulating the processes of fusion and release, but the
      mechanisms involved are only starting to be uncovered. Here we review recent
      evidence that SNARE TMDs exert influence by regulating the dynamics of the fusion
      pore, the initial aqueous connection between the vesicular lumen and the
      extracellular space. Even after the fusion pore is established, hormone release
      by neuroendocrine cells is tightly controlled, and the same may be true of
      neurotransmitter release by neurons. The dynamics of the fusion pore can regulate
      the kinetics of cargo release and the net amount released, and can determine the
      mode of vesicle recycling. Manipulations of SNARE TMDs were found to affect
      fusion pore properties profoundly, both during exocytosis and in biochemical
      reconstitutions. To explain these effects, TMD flexibility, and interactions
      among TMDs or between TMDs and lipids have been invoked. Exocytosis has provided
      the best setting in which to unravel the underlying mechanisms, being unique
      among membrane fusion reactions in that single fusion pores can be probed using
      high-resolution methods. An important role will likely be played by methods that
      can probe single fusion pores in a biochemically defined setting which have
      recently become available. Finally, computer simulations are valuable mechanistic
      tools because they have the power to access small length scales and very short
      times that are experimentally inaccessible.

PMID- 29066951
TI  - Connexin43- and Pannexin-Based Channels in Neuroinflammation and Cerebral
      Neuropathies.
AB  - Connexins (Cx) are largely represented in the central nervous system (CNS) with
      11 Cx isoforms forming intercellular channels. Moreover, in the CNS, Cx43 can
      form hemichannels (HCs) at non-junctional membrane as does the related channel
      forming Pannexin1 (Panx1) and Panx2. Opening of Panx1 channels and Cx43 HCs
      appears to be involved in inflammation and has been documented in various CNS
      pathologies. Over recent years, evidence has accumulated supporting a link
      between inflammation and cerebral neuropathies (migraine, Alzheimer's disease
      (AD), Parkinson's disease (PD), major depressive disorder, autism spectrum
      disorder (ASD), epilepsy, schizophrenia, bipolar disorder). Involvement of Panx
      channels and Cx43 HCs has been also proposed in pathophysiology of neurological
      diseases and psychiatric disorders. Other studies showed that following
      inflammatory injury of the CNS, Panx1 activators are released and prolonged
      opening of Panx1 channels triggers neuronal death. In neuropsychiatric diseases,
      comorbidities are frequently present and can aggravate the symptoms and make
      therapeutic management more complex. The high comorbidity between some
      neuropathies can be partially understood by the fact that these diseases share a
      common etiology involving inflammatory pathways and Panx1 channels or Cx43 HCs.
      Thus, anti-inflammatory therapy opens perspectives of targets for new treatments
      and could have real potential in controlling a cerebral neuropathy and some of
      its comorbidities. The purpose of this mini review is to provide information of
      our knowledge on the link between Cx43- and Panx-based channels, inflammation and
      cerebral neuropathies.

PMID- 29066947
TI  - Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation.
AB  - The goal of this review is to describe in what ways feedback or adaptive
      stimulation may be delivered and adjusted based on relevant biomarkers. Specific
      treatment mechanisms underlying therapeutic brain stimulation remain unclear, in
      spite of the demonstrated efficacy in a number of nervous system diseases. Brain
      stimulation appears to exert widespread influence over specific neural networks
      that are relevant to specific disease entities. In awake patients, activation or
      suppression of these neural networks can be assessed by either symptom
      alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which
      may be predictive of expected symptomatic treatment. Secondary verification of
      network activation through specific biomarkers that are linked to symptomatic
      disease improvement may be useful for several reasons. For example, these
      biomarkers could aid optimal intraoperative localization, possibly improve
      efficacy or efficiency (i.e., reduced power needs), and provide long-term
      adaptive automatic adjustment of stimulation parameters. Possible biomarkers for
      use in portable or implanted devices span from ongoing physiological brain
      activity, evoked local field potentials (LFPs), and intermittent pathological
      activity, to wearable devices, biochemical, blood flow, optical, or magnetic
      resonance imaging (MRI) changes, temperature changes, or optogenetic signals.
      First, however, potential biomarkers must be correlated directly with symptom or
      disease treatment and network activation. Although numerous biomarkers are under
      consideration for a variety of stimulation indications the feasibility of these
      approaches has yet to be fully determined. Particularly, there are critical
      questions whether the use of adaptive systems can improve efficacy over
      continuous stimulation, facilitate adjustment of stimulation interventions and
      improve our understanding of the role of abnormal network function in disease
      mechanisms.

PMID- 29066952
TI  - The Sleep-Wake Cycle in the Nicotinic Alpha-9 Acetylcholine Receptor Subunit
      Knock-Out Mice.
AB  - There is a neural matrix controlling the sleep-wake cycle (SWC) embedded within
      high ranking integrative mechanisms in the central nervous system. Nicotinic
      alpha-9 acetylcholine receptor subunit (alpha-9 nAChR) participate in
      physiological processes occurring in sensory, endocrine and immune systems. There
      is a relationship between the SWC architecture, body homeostasis and sensory
      afferents so that disruption of afferent signaling is expected to affect the
      temporal organization of sleep and wake states. The analysis of the SWC of 9
      nAChR knock-out animals may help to reveal the contribution of alpha-9 nAChR to
      sleep chronobiological determinants. Here we explore the polysomnogram in
      chronically implanted alpha-9 nAChR knock-out (KO) and wild-type (WT) individuals
      of the hybrid CBA/Sv129 mouse strain. Records were obtained in isolation chambers
      under a stable 12:12 light:dark cycle (LD). To unmask the 24-h modulation of the
      SWC a skeleton photoperiod (SP) protocol was performed. Under LD the daily quota
      (in %) of wakefulness (W), NREM sleep and REM sleep obtained in KO and WT animals
      were 45, 48 and 7, and 46, 46 and 8 respectively. Both groups exhibit nocturnal
      phase preference of W as well as diurnal and unimodal phase preference of NREM
      and REM sleep. The acrophase mean angles of KO vs. WT genotypes were not
      different (Zeitgeber Time: 6.5 vs. 14.9 for W, 4.3 vs. 2.8 for NREM sleep and 5.3
      vs. 3.4 for REM sleep, respectively). Transference to SP do not affect daily
      state quotas, phase preferences and acrophases among genotypes. Unmasking
      phenomena of the SWC such as wake increment during the rest phase under SP was
      evident only among WT mice suggesting the involvement of retinal structures
      containing alpha-9 nAChR in masking processes. Furthermore, KO animals exhibit
      longer NREM and REM sleep episodes that is independent of illumination
      conditions. Consolidated diurnal NREM sleep contributed to obtain higher values
      of NREM sleep delta-EEG activity among KO mice during rest phase. In conclusion,
      circadian and sleep homeostatic aspects of the SWC are operative among alpha-9
      nAChR KO animals. We propose that alpha-9 nAChR participate in retinal signaling
      processes responsible of the positive masking of sleep by light.

PMID- 29066953
TI  - Disturbances in the FGFR1-5-HT1A Heteroreceptor Complexes in the Raphe
      Hippocampal 5-HT System Develop in a Genetic Rat Model of Depression.
AB  - The FGFR1-5-HT1A heteroreceptor complexes are involved in neuroplasticity in the
      rat hippocampus and in the mesencephalic raphe 5-HT nerve cells. There exists a 5
      HT1A protomer enhancement of FGFR1 protomer signaling. Acute and 10 day treatment
      with intracerebroventricular (i.c.v.) FGF-2 and the 5-HT1A agonist 8-OH-DPAT
      produced enhanced antidepressant effects in the forced swim test (FST). We
      studied in the current work the disturbances in the FGFR1-5-HT1A heterocomplexes
      in a genetic rat model of depression, the Flinders sensitive line (FSL) rats of
      Sprague-Dawley (SD) origin, by means of neurochemical, neurophysiological and
      behavioral techniques. In control SD rats, the FGFR1 agonist SUN11602 and FGF2
      produced a significant reduction of G protein-coupled inwardly rectifying K+
      channel (GIRK) currents induced by 8-OH-DPAT in the CA1 area of the hippocampus.
      In FSL rats, only i.c.v. 8-OH-DPAT alone treatment produced a significant
      reduction in the immobility time. The combined i.c.v. treatment (FGF2 + 8-OH
      DPAT) in FSL rats did not cause a significant decrease in immobility time in the
      FST. However, in the SD rats this combined treatment produced a significant
      reduction. Furthermore, in the FSL rat a significant increase in the density of
      FGFR1-5-HT1A proximity ligation assay (PLA) positive clusters was only found
      after i.c.v. 8-OH-DPAT treatment alone in the CA2 and CA3 areas. In the SD rat a
      significant increase in the density of specific PLA clusters was only observed in
      the CA2 area of the i.c.v. combined treatment (FGF2 + 8-OH-DPAT) group. No
      treatment led to significant changes in the PLA clusters of the dorsal raphe in
      the FSL rat. However, significant changes in the density of specific PLA clusters
      were only found in the dorsal raphe of SD rats after combined treatment and
      treatment with 8-OH-DPAT alone. The results indicate that in FSL rats compared
      with SD rats alterations may develop in the ability of 8-OH-DPAT and combined
      FGFR1 and 5-HT1A agonist treatment to increase the density of FGFR1-5-HT1A
      heteroreceptor complexes of the dorsal raphe. It is proposed that such deficits
      in FSL rats may possibly reflect a failure of the combined agonist treatment to
      uncouple the 5-HT1A autoreceptors from the GIRK channels. This may contribute to
      the failure of producing antidepressant-like effects in the FSL rat by combined
      agonist treatment as seen in the SD rat. The antidepressant-like effects seen
      with the 5-HT1A agonist alone treatment in FSL but not in SD rats may instead
      involve significant increases in the FGFR1-5-HT1A complexes of the CA2 and CA3
      areas of the hippocampus.

PMID- 29066954
TI  - Visual Neurons in the Superior Colliculus Innervated by Islet2+ or Islet2-
      Retinal Ganglion Cells Display Distinct Tuning Properties.
AB  - Throughout the visual system, different subtypes of neurons are tuned to distinct
      aspects of the visual scene, establishing parallel circuits. Defining the
      mechanisms by which such tuning arises has been a long-standing challenge for
      neuroscience. To investigate this, we have focused on the retina's projection to
      the superior colliculus (SC), where multiple visual neuron subtypes have been
      described. The SC receives inputs from a variety of retinal ganglion cell (RGC)
      subtypes; however, which RGCs drive the tuning of different SC neurons remains
      unclear. Here, we pursued a genetic approach that allowed us to determine the
      tuning properties of neurons innervated by molecularly defined subpopulations of
      RGCs. In homozygous Islet2-EphA3 knock-in (Isl2EA3/EA3) mice, Isl2+ and Isl2-
      RGCs project to non-overlapping sub-regions of the SC. Based on molecular and
      anatomic data, we show that significantly more Isl2- RGCs are direction-selective
      (DS) in comparison with Isl2+ RGCs. Targeted recordings of visual responses from
      each SC sub-region in Isl2EA3/EA3 mice revealed that Isl2- RGC-innervated neurons
      were significantly more DS than those innervated by Isl2+ RGCs. Axis-selective
      (AS) neurons were found in both sub-regions, though AS neurons innervated by
      Isl2+ RGCs were more tightly tuned. Despite this segregation, DS and AS neurons
      innervated by Isl2+ or Isl2- RGCs did not differ in their spatial summation or
      spatial frequency (SF) tuning. Further, we did not observe alterations in
      receptive field (RF) size or structure of SC neurons innervated by Isl2+ or Isl2-
      RGCs. Together, these data show that innervation by Isl2+ and Isl2- RGCs results
      in distinct tuning in the SC and set the stage for future studies investigating
      the mechanisms by which these circuits are built.

PMID- 29066955
TI  - Reducing Extracellular Ca2+ Induces Adenosine Release via Equilibrative
      Nucleoside Transporters to Provide Negative Feedback Control of Activity in the
      Hippocampus.
AB  - Neural circuit activity increases the release of the purine neuromodulator
      adenosine into the extracellular space leading to A1 receptor activation and
      negative feedback via membrane hyperpolarization and inhibition of transmitter
      release. Adenosine can be released by a number of different mechanisms that
      include Ca2+ dependent processes such as the exocytosis of ATP. During sustained
      pathological network activity, ischemia and hypoxia the extracellular
      concentration of calcium ions (Ca2+) markedly falls, inhibiting exocytosis and
      potentially reducing adenosine release. However it has been observed that
      reducing extracellular Ca2+ can induce paradoxical neural activity and can also
      increase adenosine release. Here we have investigated adenosine signaling and
      release mechanisms that occur when extracellular Ca2+ is removed. Using
      electrophysiology and microelectrode biosensor measurements we have found that
      adenosine is directly released into the extracellular space by the removal of
      extracellular Ca2+ and controls the induced neural activity via A1 receptor
      mediated membrane potential hyperpolarization. Following Ca2+ removal, adenosine
      is released via equilibrative nucleoside transporters (ENTs), which when blocked
      leads to hyper-excitation. We propose that sustained action potential firing
      following Ca2+ removal leads to hydrolysis of ATP and a build-up of intracellular
      adenosine which then effluxes into the extracellular space via ENTs.

PMID- 29066956
TI  - Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein
      in GABAergic Interneurons in the Prefrontal Cortex.
AB  - Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted
      glycoprotein that binds CRH with very high affinity to modulate CRH receptor
      activity. CRH-BP is widely expressed throughout the brain, with particularly high
      expression in regions such as the amygdala, hippocampus, ventral tegmental area
      and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress
      related psychiatric disorders and addiction, with the PFC being a potential site
      of interest. However, the molecular phenotype of CRH-BP-expressing cells in this
      region has not been well-characterized. In the current study, we sought to
      determine the cell type-specific expression of CRH-BP in the PFC to begin to
      define the neural circuits in which this key regulator is acting. To characterize
      the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized
      dual in situ hybridization to examine the cellular colocalization of CRH-BP mRNA
      with vesicular glutamate transporter (VGLUT) or glutamic acid decarboxylase (GAD)
      mRNA in different subregions of the PFC. We show that CRH-BP is expressed
      predominantly in GABAergic interneurons of the PFC, as revealed by the high
      degree of colocalization (>85%) between CRH-BP and GAD. To further characterize
      the expression of CRH-BP in this heterogenous group of inhibitory neurons, we
      examined the colocalization of CRH-BP with various molecular markers of GABAergic
      interneurons, including parvalbumin (PV), somatostatin (SST), vasoactive
      intestinal peptide (VIP) and cholecystokinin (CCK). We demonstrate that CRH-BP is
      colocalized predominantly with SST in the PFC, with lower levels of
      colocalization in PV- and CCK-expressing neurons. Our results provide a more
      comprehensive characterization of the cell type-specific expression of CRH-BP and
      begin to define its potential role within circuits of the PFC. These results will
      serve as the basis for future in vivo studies to manipulate CRH-BP in a cell type
      specific manner to better understand its role in stress-related psychiatric
      disorders, including anxiety, depression and addiction.

PMID- 29066957
TI  - Effects of a 5-HT1B Receptor Agonist on Locomotion and Reinstatement of Cocaine
      Conditioned Place Preference after Abstinence from Repeated Injections in Mice.
AB  - 5-HT1B receptors (5-HT1BRs) modulate behavioral effects of cocaine. Here we
      examined the effects of the 5-HT1BR agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4
      pyridinyl)-1H-pyrrolo[3,2-b]pyridine (CP94253) on spontaneous and cocaine-induced
      locomotion and on cocaine-primed reinstatement of conditioned place preference
      (CPP) in male mice given daily repeated injections of either saline or cocaine
      (15 mg/kg, IP) for 20 days. In the locomotor activity experiment, testing
      occurred both 1 and 20 days after the final injection. In the CPP experiment,
      mice underwent conditioning procedures while receiving the last of their daily
      injections, which were given either during or >=2 h after CPP procedures. The CPP
      procedural timeline consisted of baseline preference testing (days 12-13 of the
      chronic regimen), conditioning (days 14-19, 2 daily 30-min sessions separated by
      5 h), CPP test (day 21), extinction (days 22-34; no injections), CPP extinction
      test (day 35), and reinstatement test (day 36). Mice that had not extinguished
      received additional extinction sessions prior to reinstatement testing on day 42.
      On test days, mice were pretreated with either saline or CP94253 (10 mg/kg, IP).
      Testing began 30 min later, immediately after mice were primed with either saline
      or cocaine (5 mg/kg for locomotion; 15 mg/kg for reinstatement). We found that
      CP94253 increased spontaneous locomotion in mice receiving repeated injections of
      either saline or cocaine when tested 1 day after the last injection, but had no
      effect on spontaneous locomotion after 20 days abstinence from repeated
      injections. Surprisingly, cocaine-induced locomotion was sensitized regardless of
      whether the mice had received repeated saline or cocaine. CP94253 attenuated
      expression of the sensitized locomotion after 20 days abstinence. A control
      experiment in noninjected, drug-naive mice showed that CP94253 had no effect on
      spontaneous or cocaine-induced locomotion. Mice reinstated cocaine-CPP when given
      a cocaine prime, and CP94253 pretreatment attenuated cocaine reinstatement.The
      findings suggest that stress from repeated saline injections and/or co-housing
      with cocaine-injected mice may cross-sensitize with cocaine effects on locomotion
      and that CP94253 attenuates these effects, as well as reinstatement of cocaine
      CPP. This study supports the idea that 5-HT1BR agonists may be useful anti
      cocaine medications.

PMID- 29066958
TI  - Origins of Aminergic Regulation of Behavior in Complex Insect Social Systems.
AB  - Neuromodulators are conserved across insect taxa, but how biogenic amines and
      their receptors in ancestral solitary forms have been co-opted to control
      behaviors in derived socially complex species is largely unknown. Here we explore
      patterns associated with the functions of octopamine (OA), serotonin (5-HT) and
      dopamine (DA) in solitary ancestral insects and their derived functions in
      eusocial ants, bees, wasps and termites. Synthesizing current findings that
      reveal potential ancestral roles of monoamines in insects, we identify
      physiological processes and conserved behaviors under aminergic control, consider
      how biogenic amines may have evolved to modulate complex social behavior, and
      present focal research areas that warrant further study.

PMID- 29066960
TI  - Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress.
AB  - Increased reactivity to stress is maladaptive and linked to abnormal behaviors
      and psychopathology. Chronic unpredictable stress (CUS) alters catecholaminergic
      neurotransmission and remodels neuronal circuits involved in learning, attention
      and decision making. Glial-derived neurotrophic factor (GDNF) is essential for
      the physiology and survival of dopaminergic neurons in substantia nigra and of
      noradrenergic neurons in the locus coeruleus. Up-regulation of GDNF expression
      during stress is linked to resilience; on the other hand, the inability to up
      regulate GDNF in response to stress, as a result of either genetic or epigenetic
      modifications, induces behavioral alterations. For example, GDNF-deficient mice
      exposed to chronic stress exhibit alterations of executive function, such as
      increased temporal discounting. Here we investigated the effects of CUS on latent
      inhibition (LI), a measure of selective attention and learning, in GDNF
      heterozygous (HET) mice and their wild-type (WT) littermate controls. No
      differences in LI were found between GDNF HET and WT mice under baseline
      experimental conditions. However, following CUS, GDNF-deficient mice failed to
      express LI. Moreover, stressed GDNF-HET mice, but not their WT controls, showed
      decreased neuronal activation (number of c-Fos positive neurons) in the nucleus
      accumbens shell and increased activation in the nucleus accumbens core, both key
      regions in the expression of LI. Our results add LI to the list of behaviors
      affected by chronic stress and support a role for GDNF deficits in stress-induced
      pathological behaviors relevant to schizophrenia and other psychiatric disorders.

PMID- 29066963
TI  - Can Neuroscience Assist Us in Constructing Better Patterns of Economic Decision
      Making?
AB  - We draw on outstanding research (Sanfey et al., 2006; McCabe, 2008; Bernheim,
      2009; Camerer, 2013; Radu and McClure, 2013; Declerck and Boone, 2016) to
      substantiate that neuroeconomics covers the investigation of the biological
      microfoundations of economic cognition and economic conduct, attempts to prove
      that a superior grasp of how choices are made brings about superior expectations
      regarding which options are selected, preserves the strictness of economic
      analysis in defining value-based decision, and associates imaging techniques with
      economic pattern to explain how individuals decide on a strategy taking into
      account various possible choices. Neuroeconomics is adequately prepared to
      regulate the notion of how choices are determined by mental states. The position
      that will be elaborated in this article is that neuroeconomic patterns are
      enabled and enhanced in descriptive capacity by psychological outcomes and
      substantiated in biological processes. Advancement in neuroeconomics takes place
      when outcomes from distinct procedures are coherent with an ordinary mechanistic
      clarification of what generates choice, construed by a computational pattern. We
      will develop this point further by proving that economics improves the concerted
      effort of neuroeconomics by using its observations in the various results that
      may stem from the planned and market interplays of diverse participants, and via
      a series of accurate, explicit, mathematical patterns to construe such interplays
      and results. Neuroeconomics experiments employ a mixture of brain
      imaging/stimulation tests advanced in the cognitive neurosciences and
      microeconomic systems/game theory tests advanced in the economic sciences. Our
      analyses indicate that neuroeconomics aims to employ the supplementary input
      gained from brain investigations, associated with the decision maker's selection,
      with the purpose of better grasping the cogitation process and to utilize the
      outcomes to enhance economic patterns.

PMID- 29066962
TI  - Self-Referential Information Alleviates Retrieval Inhibition of Directed
      Forgetting Effects-An ERP Evidence of Source Memory.
AB  - Directed forgetting (DF) assists in preventing outdated information from
      interfering with cognitive processing. Previous studies pointed that self
      referential items alleviated DF effects due to the elaboration of encoding
      processes. However, the retrieval mechanism of this phenomenon remains unknown.
      Based on the dual-process framework of recognition, the retrieval of self
      referential information was involved in familiarity and recollection. Using
      source memory tasks combined with event-related potential (ERP) recording, our
      research investigated the retrieval processes of alleviative DF effects elicited
      by self-referential information. The FN400 (frontal negativity at 400 ms) is a
      frontal potential at 300-500 ms related to familiarity and the late positive
      complex (LPC) is a later parietal potential at 500-800 ms related to
      recollection. The FN400 effects of source memory suggested that familiarity
      processes were promoted by self-referential effects without the modulation of to
      be-forgotten (TBF) instruction. The ERP results of DF effects were involved with
      LPCs of source memory, which indexed retrieval processing of recollection. The
      other-referential source memory of TBF instruction caused the absence of LPC
      effects, while the self-referential source memory of TBF instruction still
      elicited the significant LPC effects. Therefore, our neural findings suggested
      that self-referential processing improved both familiarity and recollection.
      Furthermore, the self-referential processing advantage which was caused by the
      autobiographical retrieval alleviated retrieval inhibition of DF, supporting that
      the self-referential source memory alleviated DF effects.

PMID- 29066959
TI  - Gene Network Construction from Microarray Data Identifies a Key Network Module
      and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.
AB  - As humans age many suffer from a decrease in normal brain functions including
      spatial learning impairments. This study aimed to better understand the molecular
      mechanisms in age-associated spatial learning impairment (ASLI). We used a
      mathematical modeling approach implemented in Weighted Gene Co-expression Network
      Analysis (WGCNA) to create and compare gene network models of young (learning
      unimpaired) and aged (predominantly learning impaired) brains from a set of
      exploratory datasets in rats in the context of ASLI. The major goal was to
      overcome some of the limitations previously observed in the traditional meta- and
      pathway analysis using these data, and identify novel ASLI related genes and
      their networks based on co-expression relationship of genes. This analysis
      identified a set of network modules in the young, each of which is highly
      enriched with genes functioning in broad but distinct GO functional categories or
      biological pathways. Interestingly, the analysis pointed to a single module that
      was highly enriched with genes functioning in "learning and memory" related
      functions and pathways. Subsequent differential network analysis of this
      "learning and memory" module in the aged (predominantly learning impaired) rats
      compared to the young learning unimpaired rats allowed us to identify a set of
      novel ASLI candidate hub genes. Some of these genes show significant
      repeatability in networks generated from independent young and aged validation
      datasets. These hub genes are highly co-expressed with other genes in the
      network, which not only show differential expression but also differential co
      expression and differential connectivity across age and learning impairment. The
      known function of these hub genes indicate that they play key roles in critical
      pathways, including kinase and phosphatase signaling, in functions related to
      various ion channels, and in maintaining neuronal integrity relating to synaptic
      plasticity and memory formation. Taken together, they provide a new insight and
      generate new hypotheses into the molecular mechanisms responsible for age
      associated learning impairment, including spatial learning.

PMID- 29066961
TI  - Different Molecular/Behavioral Endophenotypes in C57BL/6J Mice Predict the Impact
      of OX1 Receptor Blockade on Binge-Like Ethanol Intake.
AB  - Ethanol (EtOH) research has focused on stages of dependence. It is of paramount
      importance to more deeply understand the neurobehavioral factors promoting
      increased risk for EtOH binge drinking during the early stages of the addiction
      cycle. The first objective of this study was to evaluate whether C57BL/6J mice
      showing high drinking in the dark (DID) exhibit neurobehavioral traits known to
      contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers
      (HD/LD), we evaluated different types of basal anxiety-like responses, EtOH
      preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA
      expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex
      (PFC) and the nucleus accumbens (NAcc). Additionally, we tested binge drinking by
      LD/HD in response to a selective OX1r antagonist following intermittent episodes
      of DID (iDID). We report that DID consistently segregates two neurobehavioral
      endophenotypes, HD vs. LD, showing differences in neophobia and/or
      impulsivity/compulsivity traits. Additionally, HD mice show decreased basal OX1r
      and OX2r mRNA expression within the NAcc and elevated OX1r within the PFC.
      Exposure to several intermittent episodes of EtOH DID triggered a rapid increase
      in EtOH intake over time in LD mice matching that observed in HD mice. Despite
      HD/LD endophenotypes did not show differences in EtOH intake, they still
      predicted the response to a pharmacological challenge with a selective OX1r
      antagonist. The present data underscore the relevance of HD/LD endophenotypes
      stemming from DID procedures for exploring neurobehavioral processes underlying
      the early stages of the addiction cycle and EtOH binge-drinking disorders.

PMID- 29066964
TI  - Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9
      Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users.
AB  - Intoxication from cannabis impairs cognitive performance, in part due to the
      effects of Delta9-tetrahydrocannabinol (THC, the primary psychoactive compound in
      cannabis) on prefrontal cortex (PFC) function. However, a relationship between
      impairment in cognitive functioning with THC administration and THC-induced
      change in hemodynamic response has not been demonstrated. We explored the
      feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the
      functional changes of the human PFC associated with cannabis intoxication and
      cognitive impairment. Eighteen adult regular cannabis users (final sample, n =
      13) performed a working memory task (n-back) during fNIRS recordings, before and
      after receiving a single dose of oral synthetic THC (dronabinol; 20-50 mg).
      Functional data were collected using a continuous-wave NIRS device, in which 8
      Sources and 7 detectors were placed on the forehead, resulting in 20 channels
      covering PFC regions. Physiological changes and subjective intoxication measures
      were collected. We found a significant increase in the oxygenated hemoglobin
      (HbO) concentration after THC administration in several channels on the PFC
      during both the high working memory load (2-back) and the low working memory load
      (0-back) condition. The increased HbO response was accompanied by a trend toward
      an increased number of omission errors after THC administration. The current
      study suggests that cannabis intoxication is associated with increases in
      hemodynamic blood flow to the PFC, and that this increase can be detected with
      fNIRS.

PMID- 29066965
TI  - On Why Targets Evoke P3 Components in Prediction Tasks: Drawing an Analogy
      between Prediction and Matching Tasks.
AB  - P3 is the most conspicuous component in recordings of stimulus-evoked EEG
      potentials from the human scalp, occurring whenever some task has to be performed
      with the stimuli. The process underlying P3 has been assumed to be the updating
      of expectancies. More recently, P3 has been related to decision processing and to
      activation of established stimulus-response associations (S/R-link hypothesis).
      However, so far this latter approach has not provided a conception about how to
      explain the occurrence of P3 with predicted stimuli, although P3 was originally
      discovered in a prediction task. The present article proposes such a conception.
      We assume that the internal responses right or wrong both become associatively
      linked to each predicted target and that one of these two response alternatives
      gets activated as a function of match or mismatch of the target to the preceding
      prediction. This seems similar to comparison tasks where responses depend on the
      matching of the target stimulus with a preceding first stimulus (S1). Based on
      this idea, this study compared the effects of frequencies of first events
      (predictions or S1) on target-evoked P3s in prediction and comparison tasks.
      Indeed, frequencies not only of targets but also of first events had similar
      effects across tasks on target-evoked P3s. These results support the notion that
      P3 evoked by predicted stimuli reflects activation of appropriate internal
      "match" or "mismatch" responses, which is compatible with S/R-link hypothesis.

PMID- 29066966
TI  - Signal Transmission of Biological Reaction-Diffusion System by Using
      Synchronization.
AB  - Molecular signal transmission in cell is very crucial for information exchange.
      How to understand its transmission mechanism has attracted many researchers. In
      this paper, we prove that signal transmission problem between neural tumor
      molecules and drug molecules can be achieved by synchronous control. To achieve
      our purpose, we derive the Fokker-Plank equation by using the Langevin equation
      and theory of random walk, this is a model which can express the concentration
      change of neural tumor molecules. Second, according to the biological character
      that vesicles in cell can be combined with cell membrane to release the cargo
      which plays a role of signal transmission, we preliminarily analyzed the
      mechanism of tumor-drug molecular interaction. Third, we propose the view of
      synchronous control which means the process of vesicle docking with their target
      membrane is a synchronization process, and we can achieve the precise treatment
      of disease by using synchronous control. We believe this synchronous control
      mechanism is reasonable and two examples are given to illustrate the correctness
      of our results obtained in this paper.

PMID- 29066967
TI  - The End Is the Beginning: Parkinson's Disease in the Light of Brain Imaging.
AB  - Parkinson's disease (PD), the most common neurodegenerative disorder, is
      characterized by abnormal accumulation of alpha-synuclein aggregates known as
      Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent
      neuroimaging studies suggest that in the early phases of PD, synaptic and axonal
      damage anticipate the onset of a frank neuronal death. Paralleling, even post
      mortem studies on the brain of affected patients and on animal models support
      that synapses might represent the primary sites of functional and pathological
      changes. Indeed, alpha-synuclein microaggregation and spreading at terminals, by
      dysregulating the synaptic junction, would block neurotransmitter release, thus
      triggering a retrograde neurodegenerative process ending with neuronal cell loss
      by proceeding through the axons. Rather than neurodegeneration, loss of
      dopaminergic neuronal endings and axons could thus underlie the onset of
      connectome dysfunction and symptoms in PD and parkinsonisms. However, the
      manifold biases deriving from the interpretation of human brain imaging data
      hinder the validation of this hypothesis. Here, we present pivotal evidence
      supporting that novel comparative brain imaging studies, in patients and
      experimental models of PD in preliminary stages of disease, could be instrumental
      for proving whether synaptic endings are the sites where degeneration begins and
      initiating the factual achievement of disease modifying approaches. The need for
      such investigations is timely to define an early therapeutic window of
      intervention to attempt disease halting by terminal and/or axonal healing.

PMID- 29066968
TI  - Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by
      Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from
      Pharmacokinetics in Rats and Human.
AB  - Physiologically based pharmacokinetic (PBPK)/pharmacodynamic (PD) models can
      contribute to animal-to-human extrapolation and therapeutic dose predictions.
      Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran
      have been completed. In this paper, a potentially effective dose for buagafuran
      of 30 mg t.i.d. in human was estimated based on the human brain concentration
      predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the
      PBPK/PD model for buagafuran in rat which related the brain tissue concentrations
      of buagafuran and the times of animals entering the open arms in the
      pharmacological model of elevated plus-maze. Buagafuran concentrations in human
      plasma were fitted and brain tissue concentrations were predicted by using a
      human PBPK model in which the predicted plasma profiles were in good agreement
      with observations. The results provided supportive data for the rational use of
      buagafuran in clinic.

PMID- 29066970
TI  - Hupresin Retains Binding Capacity for Butyrylcholinesterase and
      Acetylcholinesterase after Sanitation with Sodium Hydroxide.
AB  - Hupresin is a new affinity resin that binds butyrylcholinesterase (BChE) in human
      plasma and acetylcholinesterase (AChE) solubilized from red blood cells (RBC).
      Hupresin is available from the CHEMFORASE company. BChE in human plasma binds to
      Hupresin and is released with 0.1 M trimethylammonium bromide (TMA) with full
      activity and 10-15% purity. BChE immunopurified from plasma by binding to
      immobilized monoclonal beads has fewer contaminating proteins than the one-step
      Hupresin-purified BChE. However, when affinity chromatography on Hupresin follows
      ion exchange chromatography at pH 4.5, BChE is 99% pure. The membrane bound AChE,
      solubilized from human RBC with 0.6% Triton X-100, binds to Hupresin and remains
      bound during washing with sodium chloride. Human AChE is not released in
      significant quantities with non-denaturing solvents, but is recovered in 1%
      trifluoroacetic acid. The denatured, partially purified AChE is useful for
      detecting exposure to nerve agents by mass spectrometry. Our goal was to
      determine whether Hupresin retains binding capacity for BChE and AChE after
      Hupresin is washed with 0.1 M NaOH. A 2 mL column of Hupresin equilibrated in 20
      mM TrisCl pH 7.5 was used in seven consecutive trials to measure binding and
      recovery of BChE from 100 mL human plasma. Between each trial the Hupresin was
      washed with 10 column volumes of 0.1 M sodium hydroxide. A similar trial was
      conducted with red blood cell AChE in 0.6% Triton X-100. It was found that the
      binding capacity for BChE and AChE was unaffected by washing Hupresin with 0.1 M
      sodium hydroxide. Hupresin could be washed with sodium hydroxide at least seven
      times without losing binding capacity.

PMID- 29066969
TI  - Improved Progression-Free Survival in Irinotecan-Treated Metastatic Colorectal
      Cancer Patients Carrying the HNF1A Coding Variant p.I27L.
AB  - Hepatocyte nuclear factor 1-alpha (HNF1A) is a liver-enriched transcription
      factor that plays a key role in many aspects of hepatic functions including
      detoxification processes. We examined whether HNF1A polymorphisms are associated
      with clinical outcomes in two independent cohorts combining 417 European ancestry
      patients with metastatic colorectal cancer (mCRC) treated with irinotecan-based
      chemotherapy. The intronic rs2244608A>G marker was predictive of an improved
      progression-free survival with a trend in the Canadian cohort and reaching
      significance in the Italian cohort, with hazard ratios (HR) of 0.74 and 0.72, P =
      0.076 and 0.038, respectively. A strong association between rs2244608A>G and
      improved PFS was found in the combined analysis of both cohorts (HR = 0.72; P =
      0.002). Consistent with an altered HNF1A function, mCRC carriers of the
      rs2244608G minor allele displayed enhanced drug exposure by 45% (P = 0.032)
      compared to non-carriers. In Caucasians, rs2244608A>G is in strong linkage with
      the coding variant rs1169288c.79A>C (HNF1A p.I27L). In healthy donors, we
      observed an altered hepatic (ABCC1, P = 0.009, ABCC2, P = 0.048 and CYP3A5, P =
      0.001; n = 89) and intestinal (TOP1, P = 0.004; n = 75) gene expression
      associated with the rs1169288C allele. In addition, the rs1169288C polymorphism
      could significantly increase the ABCC1 promoter activity by 27% (P = 0.008) and
      15% (P = 0.041) in the human kidney HEK293 and the human liver HepG2 cell lines,
      respectively. Our findings suggest that the HNF1A rs2244608, or the tightly
      linked functional coding variant p.I27L, might be a potential prognostic marker
      with irinotecan-based regimens.

PMID- 29066971
TI  - The Sigma-2 Receptor Selective Agonist Siramesine (Lu 28-179) Decreases Cocaine
      Reinforced Pavlovian Learning and Alters Glutamatergic and Dopaminergic Input to
      the Striatum.
AB  - Drug addiction is a chronic, debilitating disease that affects millions of people
      around the world causing a substantial societal burden. Despite decades of
      research efforts, treatment possibilities remain limited and relapse represents
      the most treatment-resistant element. Neurosteroid sigma-1 receptors have been
      meticulously studied in psychostimulant reinforced Pavlovian learning, while the
      sigma-2 receptor subtype has remained unexplored. Recent development of selective
      sigma-2 receptor ligands have now made it possible to investigate if the sigma-2
      receptor system is a potential target to treat drug addiction. We examined the
      effect of the sigma-2 receptor agonist Siramesine (Lu 28-179) on cocaine
      associated locomotion, Pavlovian learning, and reward neurocircuitry using
      electrophysiology recordings and in vivo microdialysis. We found that Siramesine
      significantly attenuated conditioned place preference acquisition and expression,
      as well as it completely blocked cocaine-primed reinstatement. Siramesine, in a
      similar manner as the selective sigma-1 receptor antagonist BD 1063, decreased
      acute locomotor responses to cocaine. Immunohistochemistry suggests co-expression
      of progesterone receptor membrane component 1/sigma-2 receptors and vesicular
      glutamate transporter 1 in presynaptic boutons of the nucleus accumbens (NAc).
      Whole-cell voltage clamp recordings of neurons in the NAc indicated that
      Siramesine decreases the presynaptic release probability of glutamate. Further,
      we demonstrated, via in vivo microdialysis, that Siramesine significantly
      decreased cocaine-evoked dopamine release in the striatum of freely moving mice.
      Collectively, these findings demonstrate that sigma-2 receptors regulate
      neurocircuitry responsible for positive reinforcement and thereby play a role in
      cocaine-reinforced Pavlovian behaviors.

PMID- 29066972
TI  - Adapting Pharmacoeconomics to Shape Efficient Health Systems en Route to UHC -
      Lessons from Two Continents.
AB  - Background: Pharmacoeconomics is receiving increasing attention globally as a set
      of tools ensuring efficient use of resources in health systems, albeit with
      different applications depending on the contextual, cultural and development
      stages of each country. The factors guiding design, implementation and
      optimisation of pharmacoeconomics as a steering tool under the universal health
      coverage paradigm are explored using case studies of Germany and South Africa.
      Findings: German social health insurance is subject to the efficiency precept.
      Pharmaco-regulatory tools reflect the respective framework conditions under which
      they developed at particular points in time. The institutionalization and
      integration of pharmacoeconomics into the remit of the Institute for Quality and
      Efficiency in Health Care occurred only rather recently. The road has not been
      smooth, requiring political discourse and complex processes of negotiation.
      Although enshrined in the National Drug Policy, South Africa has had a more
      fragmented approach to medicine selection and pricing with different policies in
      private and public sectors. The regulatory reform for use of pharmacoeconomic
      tools is ongoing and will be further shaped by the introduction of National
      Health Insurance. Conclusion: A clear vision or framework is essential as the
      regulatory introduction of pharmacoeconomics is not a single event but rather a
      growing momentum. The path will always be subject to influences of politics,
      economics and market forces beyond the healthcare system so delays and
      modifications to pharmacoeconomic tools are to be expected. Health systems are
      dynamic and pharmacoeconomic reforms need to be sufficiently flexible to evolve
      alongside.

PMID- 29066973
TI  - From Resistance to Sensitivity: Insights and Implications of Biphasic Modulation
      of Autophagy by Sunitinib.
AB  - Sunitinib, a multityrosine kinase inhibitor, is currently the standard first-line
      therapy in metastatic renal cell carcinoma (mRCC) and is also used in treating
      patients with pancreatic neuroendocrine and imatinib-resistant gastrointestinal
      stromal tumors (GIST). Nevertheless, most patients eventually relapse secondary
      to intrinsic or acquired sunitinib resistance. Autophagy has been reported to
      contribute to both chemo-sensitivity and -resistance. However, over the last few
      years, controversial regulatory effects of sunitinib on autophagy have been
      reported. Since gaining insights into the underlying molecular insights and
      clinical implications is indispensible for achieving optimum therapeutic
      response, this minireview article sheds light on the role of a network of
      prosurvival signaling pathways recently identified as key mediators of sunitinib
      resistance with established and emerging functions as autophagy regulators.
      Furthermore, we underscore putative prognostic biomarkers of sunitinib
      responsiveness that could guide clinicians toward patient stratification and more
      individualized therapy. Importantly, innovative therapeutic strategies/approaches
      to overcome sunitinib resistance both evaluated in preclinical studies and
      perspective clinical trials are discussed which could ultimately be translated to
      better clinical outcome.

PMID- 29066975
TI  - A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of
      HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer.
AB  - Crosstalk between the androgen receptor (AR) and other signaling pathways in
      prostate cancer (PCa) severely affects the therapeutic outcome of hormonal
      therapy. Although anti-androgen therapy prolongs overall survival in PCa
      patients, resistance rapidly develops and is often associated with increased AR
      expression and upregulation of the HER2/3-AKT signaling pathway. However, single
      agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal
      feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin
      are the active compounds in Wedelia chinensis herbal extract, and act
      synergistically to inhibit the AR activity in PCa. Here, we further demonstrated
      that an herbal extract of W. chinensis (WCE) effectively disrupted the AR,
      HER2/3, and AKT signaling networks and therefore enhanced the therapeutic
      efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in
      suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant
      PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and
      second-line antiandrogen, enzalutamide. This study provides preclinical evidence
      that the use of a defined, single plant-derived extract can augment the
      therapeutic efficacy of castration with significantly prolonged progression-free
      survival. These data also establish a solid basis for using WCE as a candidate
      agent in clinical studies.

PMID- 29066976
TI  - Impact of Pharmacist-Psychiatrist Collaborative Patient Education on Medication
      Adherence and Quality of Life (QOL) of Bipolar Affective Disorder (BPAD)
      Patients.
AB  - Background: Bipolar Affective Disorder (BPAD) is one of the leading causes of
      disability globally. Medication non-adherence and low quality of life (QOL) are
      the major challenges associated with the treatment of BPAD patients. Objective:
      Aim of this study was to assess the impact of pharmacist-psychiatrist
      collaborative patient education on medication adherence and QOL of BPAD patients.
      Methodology: A prospective randomized control study was conducted in the
      psychiatry outpatient department in a tertiary care setting. The eligible
      patients were enrolled and randomized into test (collaborative care) and control
      (usual care) groups. Patient education was provided by pharmacists to the test
      group patients, along with the usual care provided to all the patients. Patients
      were followed for three follow-ups of nearly 1 month intervals. Medication
      adherence and QOL were assessed by Medication Adherence Rating Scale and WHOQOL
      BREF questionnaire, respectively. T-test was used and P-values < 0.05 were
      considered statistically significant. Results: Out of 75 patients enrolled, 73
      patients were followed for all the three follow-ups and completed the study.
      Thirty-eight patients belonged to test and 35 were in control group. The mean age
      of patients was 34.21 +/- 10.91 years. Forty-eight (65.75%) patients belonged to
      age group of 18-39 years. There were 41 males (56.16%) and 32 female patients
      (43.83%) in the study. Mean improvement in medication adherence and QOL of the
      test and control groups were found to be 2.06 +/- 0.15 (<0.001) and 13.8 +/- 10.5
      (<0.05), respectively. Conclusion: This study concluded that pharmacist
      psychiatrist collaborative patient education can significantly improve the
      medication adherence and QOL of the BPAD patients. Statistically significant
      results indicating improved patient care and outcomes were possible when
      pharmacists worked as a team with psychiatrists.

PMID- 29066977
TI  - Anaerobic Contribution Determined in Swimming Distances: Relation with
      Performance.
AB  - Total anaerobic contribution (TAn) can be assessed by accumulated oxygen deficit,
      and through sum of glycolytic and phosphagen contribution which enable the
      evaluation of TAn without influences on mechanical parameters. However, little is
      known about the difference of TAn within swimming distances. Therefore, the
      objectives of the present study were to determine and compare the TAn in
      different performances using the backward extrapolation technique and amount of
      lactate accumulated during exercise, and relate it with swimming performance.
      Fourteen competitive swimmers performed five maximal front crawl swims of 50,
      100, 200, 400, and 800 m. The total phosphagen (AnAl) and glycolytic (AnLa)
      contributions were assumed as the fast component of post-exercise oxygen
      consumption (EPOCFAST) and amount of blood lactate accumulated during exercise,
      respectively. TAn was the sum of AnAl and AnLa. Significantly lower values of
      AnLa were observed in the 800 m (p < 0.01) than other distances. For AnAl, the 50
      m performance presented the lowest values, followed by 100 and 800 m (p < 0.01).
      The highest values of AnAl were observed in the 200 and 400 m (p > 0.13). The TAn
      was significantly higher in the 200 and 400 m performances than observed at 50
      and 800 m (p < 0.01). Anaerobic contributions were correlated with 50, 100, 200,
      and 400 m performances (p < 0.01). The AnAl contribution was not correlated with
      400 m performance. Anaerobic parameters were not correlated with 800 m
      performance. In conclusion, the highest values of anaerobic contribution were
      observed in the 200 and 400 m distances. Moreover, TAn is important to
      performances below 400 m, and may be used in training routines.

PMID- 29066978
TI  - Molecular Ecological Basis of Grasshopper (Oedaleus asiaticus) Phenotypic
      Plasticity under Environmental Selection.
AB  - While ecological adaptation in insects can be reflected by plasticity of
      phenotype, determining the causes and molecular mechanisms for phenotypic
      plasticity (PP) remains a crucial and still difficult question in ecology,
      especially where control of insect pests is involved. Oedaleus asiaticus is one
      of the most dominant pests in the Inner Mongolia steppe and represents an
      excellent system to study phenotypic plasticity. To better understand ecological
      factors affecting grasshopper phenotypic plasticity and its molecular control, we
      conducted a full transcriptional screening of O. asiaticus grasshoppers reared in
      four different grassland patches in Inner Mongolia. Grasshoppers showed different
      degrees of PP associated with unique gene expressions and different habitat plant
      community compositions. Grasshopper performance variables were susceptible to
      habitat environment conditions and closely associated with plant architectures.
      Intriguingly, eco-transcriptome analysis revealed five potential candidate genes
      playing important roles in grasshopper performance, with gene expression closely
      relating to PP and plant community factors. By linking the grasshopper
      performances to gene profiles and ecological factors using canonical regression,
      we first demonstrated the eco-transcriptomic architecture (ETA) of grasshopper
      phenotypic traits (ETAGPTs). ETAGPTs revealed plant food type, plant density,
      coverage, and height were the main ecological factors influencing PP, while
      insect cuticle protein (ICP), negative elongation factor A (NELFA), and lactase
      phlorizin hydrolase (LCT) were the key genes associated with PP. Our study gives
      a clear picture of gene-environment interaction in the formation and maintenance
      of PP and enriches our understanding of the transcriptional events underlying
      molecular control of rapid phenotypic plasticity associated with environmental
      variability. The findings of this study may also provide new targets for pest
      control and highlight the significance of ecological management practice on
      grassland conservation.

PMID- 29066979
TI  - Autonomic Dysfunction in Wilson's Disease: A Comprehensive Evaluation during a 3
      Year Follow Up.
AB  - Objectives: Wilson's disease is reported to have autonomic dysfunction, but
      comprehensive evaluation of autonomic function is lacking. Additionally, little
      is known about the change of autonomic function of Wilson's disease during
      continuous therapy. We assumed that patients with Wilson's disease had both
      sympathetic and parasympathetic autonomic impairments, and the autonomic
      dysfunction might be stable across a 3-year follow-up after years of optimal
      treatment. Methods: Twenty-six patients with Wilson's disease and twenty-six
      healthy controls were recruited. Twenty patients in the Wilson's disease group
      were examined again after a 3-year follow-up. All the participants were evaluated
      by a questionnaire on dysautonomia symptoms, 24-h blood pressure and heart rate
      monitoring, and cardiovascular autonomic function examination in various
      conditions including at rest, deep breathing, Valsalva maneuver, isometric
      handgrip test and passive tilting. Baroreflex sensitivity and spectral analyses
      were performed via trigonometric regressive spectral analysis. Results: Patients
      with Wilson's disease showed autonomic dysfunction mainly in the following
      aspects: (1) the heart rate was higher than the controls. (2) Valsalva ratio was
      lower in patients with Wilson's disease compared with the controls. (3) Heart
      rate increase during isometric hand gripping was smaller in the Wilson's disease
      patients than the controls. (4) Baroreflex sensitivity was lower during nearly
      all the cardiovascular autonomic function examinations compared with healthy
      controls. When tested 3 years later, baroreflex sensitivity at rest decreased
      compared with baseline. (5) There were mild declines of resting DBP and low
      frequency component of heart rate variability during the follow-up examination
      compared with baseline. (6) Subgroup analysis showed that patients initially
      presenting with neurological symptoms had a higher night-time heart rate, lower
      expiration: inspiration RR interval ratio (E/I ratio), lower expiration:
      inspiration RR interval difference (E-I difference), less increase of heart rate
      and diastolic blood pressure during the handgrip test, and lower baroreflex
      sensitivity during deep breathing than the control group. (7) Correlation
      analysis showed that the severity of neurological symptoms was associated with
      E/I ratio, E-I difference, Valsalva ratio, heart rate change during the handgrip
      test, and baroreflex sensitivity during deep breathing. Conclusions: The present
      study reveals cardiovascular autonomic dysfunction involving both sympathetic and
      parasympathetic branches in Wilson's disease patients, which is especially
      significant in the patients with neurological onset. Autonomic function is
      generally stable undergoing optimal maintenance treatment in patients with
      Wilson's disease. Though there might be mild changes of specific parameters.

PMID- 29066980
TI  - The Whitish Inner Mantle of the Giant Clam, Tridacna squamosa, Expresses an
      Apical Plasma Membrane Ca2+-ATPase (PMCA) Which Displays Light-Dependent Gene and
      Protein Expressions.
AB  - Giant clams live in symbiosis with extracellular zooxanthellae and display high
      rates of growth and shell formation (calcification) in light. Light-enhanced
      calcification requires an increase in the supply of Ca2+ to, and simultaneously
      an augmented removal of H+ from, the extrapallial fluid where shell formation
      occurs. We have obtained the complete coding cDNA sequence of Plasma Membrane
      Ca2+-ATPase (PMCA) from the thin and whitish inner mantle, which is in touch with
      the extrapallial fluid, of the giant clam Tridacna squamosa. The deduced PMCA
      sequence consisted of an apical targeting element. Immunofluorescence microscopy
      confirmed that PMCA had an apical localization in the shell-facing epithelium of
      the inner mantle, whereby it can actively secrete Ca2+ in exchange for H+. More
      importantly, the apical PMCA-immunofluorescence of the shell-facing epithelium of
      the inner mantle increased significantly after 12 h of exposure to light. The
      transcript and protein levels of PMCA/PMCA also increased significantly in the
      inner mantle after 6 or 12 h of light exposure. These results offer insights into
      a light-dependable mechanism of shell formation in T. squamosa and a novel
      explanation of light-enhanced calcification in general. As the inner mantle
      normally lacks light sensitive pigments, our results support a previous
      proposition that symbiotic zooxanthellae, particularly those in the colorful and
      extensible outer mantle, may act as light-sensing elements for the host clam.

PMID- 29066974
TI  - Cannabinoids Modulate Neuronal Activity and Cancer by CB1 and CB2 Receptor
      Independent Mechanisms.
AB  - Cannabinoids include the active constituents of Cannabis or are molecules that
      mimic the structure and/or function of these Cannabis-derived molecules.
      Cannabinoids produce many of their cellular and organ system effects by
      interacting with the well-characterized CB1 and CB2 receptors. However, it has
      become clear that not all effects of cannabinoid drugs are attributable to their
      interaction with CB1 and CB2 receptors. Evidence now demonstrates that
      cannabinoid agents produce effects by modulating activity of the entire array of
      cellular macromolecules targeted by other drug classes, including: other receptor
      types; ion channels; transporters; enzymes, and protein- and non-protein cellular
      structures. This review summarizes evidence for these interactions in the CNS and
      in cancer, and is organized according to the cellular targets involved. The CNS
      represents a well-studied area and cancer is emerging in terms of understanding
      mechanisms by which cannabinoids modulate their activity. Considering the CNS and
      cancer together allow identification of non-cannabinoid receptor targets that are
      shared and divergent in both systems. This comparative approach allows the
      identified targets to be compared and contrasted, suggesting potential new areas
      of investigation. It also provides insight into the diverse sources of efficacy
      employed by this interesting class of drugs. Obtaining a comprehensive
      understanding of the diverse mechanisms of cannabinoid action may lead to the
      design and development of therapeutic agents with greater efficacy and
      specificity for their cellular targets.

PMID- 29066981
TI  - Hydrogen Sulfide Attenuates Atherosclerosis in a Partially Ligated Carotid Artery
      Mouse model via Regulating Angiotensin Converting Enzyme 2 Expression.
AB  - Hydrogen sulfide has been suggested to play an essential role in atherogenesis.
      There is a paucity of information about the association between H2S and
      angiotensin converting enzyme 2 (ACE2), a novel homolog of ACE. Therefore, the
      aim of the study was to explore the role of H2S in atherosclerosis with respect
      to ACE2 both in vitro and in vivo. Here, a murine model of acutely disturbed flow
      induced atherosclerosis by left common carotid artery (LCA) partial ligation was
      utilized. We found that carotid partial ligation in high-fat fed apoE-/- mice
      significantly inhibited endogenous H2S synthesis in LCA. Application of NaHS, an
      H2S donor considerably attenuated the severity of atherosclerosis with
      upregulating carotid expression of ACE2, thus converting pro-atherosclerotic
      angiotensin II (Ang II) to anti-atherosclerotic angiotensin 1-7 (Ang-(1-7)). The
      anti-atherosclerotic effect of NaHS was dramatically abolished by treatment with
      MLN-4760, an ACE2 inhibitor. In contrast, blockage of H2S formation by DL
      propargylglycine exacerbated the burden of atherosclerotic plaques accompanied by
      inhibiting carotid expression of ACE2. At the cellular level, NaHS dose
      dependently promoted the expression of ACE2 and conversion from Ang II to Ang-(1
      7) in unstimulated or LPS-stimulated endothelial cells, thus exerting anti
      inflammatory properties. The anti-inflammatory effect of NaHS was abrogated by
      pretreatment with DX600, a selective ACE2 inhibitor. In conclusion, these data
      provide direct evidences that endogenous H2S insufficiency exists in acute flow
      disturbance-induced atherosclerosis and that application of H2S may protect
      against atherosclerosis via upregulating ACE2 expression in endothelial cells.

PMID- 29066982
TI  - Foot Placement Characteristics and Plantar Pressure Distribution Patterns during
      Stepping on Ground in Neonates.
AB  - Stepping on ground can be evoked in human neonates, though it is rather irregular
      and stereotyped heel-to-toe roll-over pattern is lacking. Such investigations can
      provide insights into the role of contact- or load-related proprioceptive
      feedback during early development of locomotion. However, the detailed
      characteristics of foot placements and their association with motor patterns are
      still incompletely documented. We elicited stepping in 33 neonates supported on a
      table. Unilateral limb kinematics, bilateral plantar pressure distribution and
      EMG activity from up to 11 ipsilateral leg muscles were recorded. Foot placement
      characteristics in neonates showed a wide variation. In ~25% of steps, the
      swinging foot stepped onto the contralateral foot due to generally small step
      width. In the remaining steps with separate foot placements, the stance phase
      could start with forefoot (28%), midfoot (47%), or heel (25%) touchdowns. Despite
      forefoot or heel initial contacts, the kinematic and loading patterns markedly
      differed relatively to toe-walking or adult-like two-peaked vertical force
      profile. Furthermore, while the general stepping parameters (cycle duration, step
      length, range of motion of proximal joints) were similar, the initial foot
      contact was consistently associated with specific center-of-pressure excursion,
      range of motion in the ankle joint, and the center-of-activity of extensor
      muscles (being shifted by ~5% of cycle toward the end of stance in the "heel"
      relative to "forefoot" condition). In sum, we found a variety of footfall
      patterns in conjunction with associated changes in motor patterns. These findings
      suggest the potential contribution of load-related proprioceptive feedback and/or
      the expression of variations in the locomotor program already during early
      manifestations of stepping on ground in human babies.

PMID- 29066984
TI  - Relating Measurement Invariance, Cross-Level Invariance, and Multilevel
      Reliability.
AB  - Data often have a nested, multilevel structure, for example when data are
      collected from children in classrooms. This kind of data complicate the
      evaluation of reliability and measurement invariance, because several properties
      can be evaluated at both the individual level and the cluster level, as well as
      across levels. For example, cross-level invariance implies equal factor loadings
      across levels, which is needed to give latent variables at the two levels a
      similar interpretation. Reliability at a specific level refers to the ratio of
      true score variance over total variance at that level. This paper aims to shine
      light on the relation between reliability, cross-level invariance, and strong
      factorial invariance across clusters in multilevel data. Specifically, we will
      illustrate how strong factorial invariance across clusters implies cross-level
      invariance and perfect reliability at the between level in multilevel factor
      models.

PMID- 29066986
TI  - The Mediating Effect of Self-Efficacy in the Connections between Strength-Based
      Parenting, Happiness and Psychological Distress in Teens.
AB  - Preliminary studies of strength-based parenting (SBP), a style of parenting that
      seeks to build strengths knowledge and strengths use in one's child, have
      reported benefits such as higher life satisfaction, subjective wellbeing, and
      positive emotions together with lower stress in children and teens. Two proximal
      mediators conveying these effects have been identified: teen's own use of
      strengths and strength-based coping, along with a small moderating effect of
      growth mindsets relating to strengths. The current study tests the potential
      mediating effect of self-efficacy, a sense of agency in life, in the relationship
      between SBP and mental health (wellbeing and illbeing) in teens. Self efficacy
      has been linked to wellbeing and strengths processes in past studies and is
      classed as a basic human need and form of eudaimonic happiness. This study
      reconfirmed the adaptive benefits of SBP in a large sample of Australian
      adolescents (N = 11,368; 59% male; Mage = 14.04, SDage = 1.99) sourced from 28
      schools. Using structural equation modeling, SBP significantly and directly
      predicted higher happiness and lower depression, with direct effects falling into
      the 85th and 95th percentile of meta-analytically derived individual differences
      effect sizes. In addition, self-efficacy was a significant partial mediator,
      accounting for 40.0% of the total effect on happiness and 52.7% of the total
      effect on distress. Self-efficacy was also a full mediator in the case of
      anxiety, with a strong indirect effect. Results suggest that building strengths
      in teens can also build self-efficacy, and given the large effect sizes, that SBP
      is a promising leverage point for increasing teen wellbeing.

PMID- 29066985
TI  - Taking Up an Active Role: Emerging Participation in Early Mother-Infant
      Interaction during Peekaboo Routines.
AB  - Dynamical systems approaches to social coordination underscore how participants'
      local actions give rise to and maintain global interactive patterns and how, in
      turn, they are also shaped by them. Developmental research can deliver important
      insights into both processes: (1) the stabilization of ways of interacting, and
      (2) the gradual shaping of the agentivity of the individuals. In this article we
      propose that infants' agentivity develops out of participation, i.e., acting a
      part in an interaction system. To investigate this development this article
      focuses on the ways in which participation in routinized episodes may shape
      infant's agentivity in social events. In contrast to existing research addressing
      more advanced forms of participating in social routines, our goal was to assess
      infants' early participation as evidence of infants' agentivity. In our study, 19
      Polish mother-infant dyads were filmed playing peekaboo when the infants were 4
      and 6 months of age. We operationalized infants' participation in the peekaboo in
      terms of their use of various behaviors across modalities during specific phases
      of the game: We included smiles, vocalizations, and attempts to cover and uncover
      themselves or their mothers. We hypothesized that infants and mothers would
      participate actively in the routine by regulating their behavior so as to adhere
      to the routine format. Furthermore, we hypothesized that infants who experienced
      more scaffolding would be able to adopt a more active role in the routine. We
      operationalized scaffolding as mothers' use of specific peekaboo structures that
      allowed infants to anticipate when it was their turn to act. Results suggested
      that infants as young as 4 months of age engaged in peekaboo and took up turns in
      the game, and that their participation increased at 6 months of age. Crucially,
      our results suggest that infants' behavior was organized by the global structure
      of the peekaboo game, because smiles, vocalizations, and attempts to uncover
      occurred significantly more often during specific phases rather than being evenly
      distributed across the whole interaction. Furthermore, the way mothers structured
      the game at 4 months predicted infant participation at both 4 and 6 months of
      age.

PMID- 29066983
TI  - Fit to Perform: An Investigation of Higher Education Music Students' Perceptions,
      Attitudes, and Behaviors toward Health.
AB  - Making music at the highest international standards can be rewarding, but it is
      also challenging, with research highlighting pernicious ways in which practicing
      and performing can affect performers' health and wellbeing. Several studies
      indicate that music students' perceptions, attitudes, and behaviors toward health
      and healthy living are less than optimal, especially considering the multiple
      physical and psychological demands of their day-to-day work. This article
      presents the results of a comprehensive screening protocol that investigated
      lifestyle and health-related attitudes and behaviors among 483 undergraduate and
      postgraduate students (mean age = 21.29 years +/- 3.64; 59% women) from ten
      conservatoires. The protocol included questionnaires measuring wellbeing, general
      health, health-promoting behaviors, perfectionism, coping, sleep quality, and
      fatigue. On each measure, the data were compared with existing published data
      from similar age groups. The results indicate that music students have higher
      levels of wellbeing and lower fatigue than comparable samples outside of music.
      However, they also reveal potentially harmful perceptions, attitudes, and
      behaviors toward health. Specifically, engagement in health responsibility and
      stress management was low, which along with high perfectionistic strivings,
      limited use of coping strategies, poor sleep quality, and low self-rated health,
      paints a troubling picture both for the music students and for those who support
      their training. The findings point to the need for more (and more effective)
      health education and promotion initiatives within music education; in particular,
      musicians should be better equipped with mental skills to cope with constant
      pressure to excel and high stress levels. In part, this calls for musicians
      themselves to engage in healthier lifestyles, take greater responsibility for
      their own health, and be aware of and act upon health information in order to
      achieve and sustain successful practice and performance. For that to happen,
      however, music educators, administrators, and policy makers must play an active
      role in providing supportive environments where health and wellbeing is
      considered integral to expert music training.

PMID- 29066987
TI  - Loss Aversion Reflects Information Accumulation, Not Bias: A Drift-Diffusion
      Model Study.
AB  - Defined as increased sensitivity to losses, loss aversion is often conceptualized
      as a cognitive bias. However, findings that loss aversion has an attentional or
      emotional regulation component suggest that it may instead reflect differences in
      information processing. To distinguish these alternatives, we applied the drift
      diffusion model (DDM) to choice and response time (RT) data in a card gambling
      task with unknown risk distributions. Loss aversion was measured separately for
      each participant. Dividing the participants into terciles based on loss aversion
      estimates, we found that the most loss-averse group showed a significantly lower
      drift rate than the other two groups, indicating overall slower uptake of
      information. In contrast, neither the starting bias nor the threshold separation
      (barrier) varied by group, suggesting that decision thresholds are not affected
      by loss aversion. These results shed new light on the cognitive mechanisms
      underlying loss aversion, consistent with an account based on information
      accumulation.

PMID- 29066988
TI  - The Status and Future of Consciousness Research.

PMID- 29066989
TI  - Own-Group Face Recognition Bias: The Effects of Location and Reputation.
AB  - In the present study, we examined whether social categorization based on
      university affiliation can induce an advantage in recognizing faces. Moreover, we
      investigated how the reputation or location of the university affected face
      recognition performance using an old/new paradigm. We assigned five different
      university labels to the faces: participants' own university and four other
      universities. Among the four other university labels, we manipulated the academic
      reputation and geographical location of these universities relative to the
      participants' own university. The results showed that an own-group face
      recognition bias emerged for faces with own-university labels comparing to those
      with other-university labels. Furthermore, we found a robust own-group face
      recognition bias only when the other university was located in a different city
      far away from participants' own university. Interestingly, we failed to find the
      influence of university reputation on own-group face recognition bias. These
      results suggest that categorizing a face as a member of one's own university is
      sufficient to enhance recognition accuracy and the location will play a more
      important role in the effect of social categorization on face recognition than
      reputation. The results provide insight into the role of motivational factors
      underlying the university membership in face perception.

PMID- 29066990
TI  - Beyond Psychometrics: The Difference between Difficult Problem Solving and
      Complex Problem Solving.
AB  - In this paper we argue that a synthesis of findings across the various sub-areas
      of research in complex problem solving and consequently progress in theory
      building is hampered by an insufficient differentiation of complexity and
      difficulty. In the proposed framework of person, task, and situation (PTS),
      complexity is conceptualized as a quality that is determined by the cognitive
      demands that the characteristics of the task and the situation impose. Difficulty
      represents the quantifiable level of a person's success in dealing with such
      demands. We use the well-documented "semantic effect" as an exemplar for testing
      some of the conceptual assumptions derived from the PTS framework. We demonstrate
      how a differentiation between complexity and difficulty can help take beyond a
      potentially too narrowly defined psychometric perspective and subsequently gain a
      better understanding of the cognitive mechanisms behind this effect. In an
      empirical study a total of 240 university students were randomly allocated to one
      of four conditions. The four conditions resulted from contrasting the semanticity
      level of the variable labels used in the CPS system (high vs. low) and two
      instruction conditions for how to explore the CPS system's causal structure
      (starting with the assumption that all relationships between variables existed
      vs. starting with the assumption that none of the relationships existed). The
      variation in the instruction aimed at inducing knowledge acquisition processes of
      either (1) systematic elimination of presumptions, or (2) systematic compilation
      of a mental representation of the causal structure underpinning the system.
      Results indicate that (a) it is more complex to adopt a "blank slate" perspective
      under high semanticity as it requires processes of inhibiting prior assumptions,
      and (b) it seems more difficult to employ a systematic heuristic when testing
      against presumptions. In combination, situational characteristics, such as the
      semanticity of variable labels, have the potential to trigger qualitatively
      different tasks. Failing to differentiate between 'task' and 'situation' as
      independent sources of complexity and treating complexity and difficulty
      synonymously threaten the validity of performance scores obtained in CPS
      research.

PMID- 29066992
TI  - When and Why Does Materialism Relate to Employees' Attitudes and Well-being: The
      Mediational Role of Need Satisfaction and Need Frustration.
AB  - Materialistic values may be detrimental for people's well-being. However, we know
      little about why (i.e., explaining mechanisms) and when (i.e., boundary
      conditions) this is the case. Although low satisfaction of the psychological
      needs is said to play a key role in this process, a recent meta-analysis
      indicates that the explaining power of need satisfaction is limited and suggests
      that need frustration may be more important. Moreover, although materialism may
      be detrimental in some life domains, studies in materialistic contexts such as
      work are lacking, particularly in the non-Western world. In response, we put need
      frustration to the fore and examine both need satisfaction and frustration as the
      underlying processes in the relation between materialism and employee attitudes
      and well-being in two Latin-American countries. The Chilean sample (N = 742)
      shows that materialism at work is associated with less positive (work
      satisfaction and engagement) and more negative (burnout and turnover intentions)
      outcomes, even when controlling for workers' income. Notably, need frustration
      explained the detrimental effects of materialism alongside need satisfaction in a
      unique manner, showing that it is essential to distinguish both constructs.
      Results were replicated in Paraguay (N = 518) using different positive
      (organizational commitment and meaning at work) and negative (negative emotions
      and job insecurity) outcomes, adding to the generalizability of our results
      across samples of different nations.

PMID- 29066993
TI  - Editorial: Diversity and Universality in Causal Cognition.

PMID- 29066991
TI  - Efficacy of Eye Movement Desensitization and Reprocessing in Children and
      Adolescent with Post-traumatic Stress Disorder: A Meta-Analysis of Randomized
      Controlled Trials.
AB  - Background: Post-traumatic stress disorder (PTSD) can occur in both adults and
      children/adolescents. Untreated PTSD can lead to negative long-term mental health
      conditions such as depression, anxiety, low self-concept, disruptive behaviors,
      and/or substance use disorders. To prevent these adverse effects, treatment of
      PTSD is essential, especially in young population due to their greater
      vulnerability. The principal aim of this meta-analysis was to examine the
      efficacy of eye movement desensitization and reprocessing (EMDR) therapy for PTSD
      symptoms in children and adolescents. Secondary objectives were to assess whether
      EMDR therapy was effective to improve depressive or anxious comorbid symptoms.
      Methods: We conducted a thorough systematic search of studies published until
      January 2017, using PubMed, Medline, Scopus, and ScienceDirect as databases. All
      randomized controlled trials with an EMDR group condition compared to a control
      group, such as treatment as usual or another psychological treatment, were
      included. Meta-analysis was conducted with MetaNSUE to avoid biases related to
      missing information. Results: Eight studies (n = 295) met our inclusion criteria.
      EMDR therapy was superior to waitlist/placebo conditions and showed comparable
      efficacy to cognitive behavior therapy (CBT) in reducing post-traumatic and
      anxiety symptoms. A similar but non-statistically significant trend was observed
      for depressive symptoms. Exploratory subgroup analyses showed that effects might
      be smaller in studies that included more males and in more recent studies.
      Conclusion: Despite the small number of publications, the obtained results
      suggest that EMDR therapy could be a promising psychotherapeutic approach for the
      treatment of PTSD and comorbid symptoms in young individuals. However, further
      research with larger samples is needed to confirm these preliminary results as
      well as to analyze differences in the efficacy of EMDR therapy versus CBT.

PMID- 29066994
TI  - A New Measurement of Internet Addiction Using Diagnostic Classification Models.
AB  - To obtain accurate, valid, and rich information from the questionnaires for
      internet addiction, a diagnostic classification test for internet addiction (the
      DCT-IA) was developed using diagnostic classification models (DCMs), a cutting
      edge psychometric theory, based on DSM-5. A calibration sample and a validation
      sample were recruited in this study to calibrate the item parameters of the DCT
      IA and to examine the sensitivity and specificity. The DCT-IA had high
      reliability and validity based on both CTT and DCMs, and had a sensitivity of
      0.935 and a specificity of 0.817 with AUC = 0.919. More important, different from
      traditional questionnaires, the DCT-IA can simultaneously provide general-level
      diagnostic information and the detailed symptom criteria-level information about
      the posterior probability of satisfying each symptom criterion in DMS-5 for each
      patient, which gives insight into tailoring individual-specific treatments for
      internet addiction.

PMID- 29066995
TI  - General Belief in a Just World Is Positively Associated with Dishonest Behavior.
AB  - According to the just-world theory, people need to - or rather want to - believe
      that they live in a just world where they will receive what they earn and
      consequently earn what they receive. In the present work, we examined the
      influence of people's general and personal beliefs in a just world (BJW) on their
      (dis)honest behavior. Given that general BJW was found to be linked to antisocial
      tendencies, we expected stronger general BJW to be linked to more dishonesty.
      Given that personal BJW was found to be correlated with trust and justice
      striving, a negative link with dishonesty could be assumed. In one study (N =
      501), we applied a common coin-toss paradigm to assess dishonesty. General BJW
      significantly predicted the probability of tossing the target outcome, that is,
      higher general BJW was linked to more dishonest behavior. This effect was found
      to be independent from personal BJW and self-reported importance of religion.
      Unexpectedly, there was no significant relationship between personal BJW and
      levels of dishonesty. These findings imply that although BJW normally serves an
      adaptive function, at least the facet general BJW has maladaptive side-effects.

PMID- 29066996
TI  - What the Dynamic Systems Approach Can Offer for Understanding Development: An
      Example of Mid-childhood Reaching.
AB  - The Dynamic Systems Approach (DSA) to development has been shown to be a
      promising theory to understand developmental changes. In this perspective, we use
      the example of mid-childhood (6- to 10-years of age) reaching to show how using
      the DSA can advance the understanding of development. Mid-childhood is an
      important developmental period that has often been overshadowed by the focus on
      the acquisition of reaching during infancy. This underrepresentation of mid
      childhood studies is unjustified, as earlier studies showed that important
      developmental changes in mid-childhood reaching occur that refine the skill of
      reaching. We review these studies here for the first time and show that different
      studies revealed different developmental trends, such as non-monotonic and linear
      trends, for variables such as movement time and accuracy at target.
      Unfortunately, proposed explanations for these developmental changes have been
      tailored to individual studies, limiting their scope. Also, explanations were
      focused on a single component or process in the system that supposedly causes
      developmental changes. Here, we propose that the DSA can offer an overarching
      explanation for developmental changes in this research field. According to the
      DSA, motor behavior emerges from interactions of multiple components entailed by
      the person, environment, and task. Changes in all these components can
      potentially contribute to the emerging behavior. We show how the principles of
      change of the DSA can be used as an overarching framework by applying these
      principles not only to development, but also the behavior itself. This underlines
      its applicability to other fields of development.

PMID- 29066997
TI  - Recommendations for the Use of Automated Gray Matter Segmentation Tools: Evidence
      from Huntington's Disease.
AB  - The selection of an appropriate segmentation tool is a challenge facing any
      researcher aiming to measure gray matter (GM) volume. Many tools have been
      compared, yet there is currently no method that can be recommended above all
      others; in particular, there is a lack of validation in disease cohorts. This
      work utilizes a clinical dataset to conduct an extensive comparison of
      segmentation tools. Our results confirm that all tools have advantages and
      disadvantages, and we present a series of considerations that may be of use when
      selecting a GM segmentation method, rather than a ranking of these tools. Seven
      segmentation tools were compared using 3 T MRI data from 20 controls, 40
      premanifest Huntington's disease (HD), and 40 early HD participants. Segmented
      volumes underwent detailed visual quality control. Reliability and repeatability
      of total, cortical, and lobular GM were investigated in repeated baseline scans.
      The relationship between each tool was also examined. Longitudinal within-group
      change over 3 years was assessed via generalized least squares regression to
      determine sensitivity of each tool to disease effects. Visual quality control and
      raw volumes highlighted large variability between tools, especially in occipital
      and temporal regions. Most tools showed reliable performance and the volumes were
      generally correlated. Results for longitudinal within-group change varied between
      tools, especially within lobular regions. These differences highlight the need
      for careful selection of segmentation methods in clinical neuroimaging studies.
      This guide acts as a primer aimed at the novice or non-technical imaging
      scientist providing recommendations for the selection of cohort-appropriate GM
      segmentation software.

PMID- 29066998
TI  - Somatotopy in the Medullary Dorsal Horn As a Basis for Orofacial Reflex Behavior.
AB  - The somatotopy of the trigeminocervical complex of the rat was defined as a basis
      for describing circuitry for reflex behaviors directed through the facial motor
      nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates
      applied to individual nerves/peripheral receptive fields showed that nerves
      innervating oropharyngeal structures projected most rostrally, followed by nerves
      innervating snout, periocular, and then periauricular receptive fields most
      caudally. Nerves innervating mucosae or glabrous receptive fields terminated
      densely in laminae I, II, and V of the trigeminocervical complex, while those
      innervating hairy skin terminated in laminae I-V. Projections to lamina II
      exhibited the most focused somatotopy when individual cases were compared.
      Retrograde transport of FluoroGold (FG) deposited into the facial motor nucleus
      resulted in labeled neurons almost solely in lamina V of the trigeminocervical
      complex. The distribution of these labeled neurons paralleled the somatotopy of
      primary afferent fibers, e.g., those labeled after FG injections into a
      functional group of motoneurons innervating lip musculature were found most
      rostrally while those labeled after injections into motoneurons innervating
      snout, periocular and preauricular muscles, respectively, were found at
      progressively more caudal levels. Anterograde transport of injections of
      biotinylated dextran amine into lamina V at different rostrocaudal levels of the
      trigeminocervical complex confirmed the notion that the somatotopy of orofacial
      sensory fields parallels the musculotopy of facial motor neurons. These data
      suggest that neurons in lamina V are important interneurons in a simple orofacial
      reflex circuit consisting of a sensory neuron, interneuron and motor neuron.
      Moreover, the somatotopy of primary afferent fibers from the head and neck
      confirms the "onion skin hypothesis" and suggests rostral cervical dermatomes
      blend seamlessly with "cranial dermatomes." The transition area between
      subnucleus interpolaris and subnucleus caudalis is addressed while the
      paratrigeminal nucleus is discussed as an interface between the somatic and
      visceral nervous systems.

PMID- 29066999
TI  - Validation of the Italian Version of the Dizziness Handicap Inventory, the
      Situational Vertigo Questionnaire, and the Activity-Specific Balance Confidence
      Scale for Peripheral and Central Vestibular Symptoms.
AB  - Neurophysiological measurements of the vestibular function for diagnosis and
      follow-up evaluations provide an objective assessment, which, unfortunately, does
      not necessarily correlate with the patients' self-feeling. The literature
      provides many questionnaires to assess the outcome of rehabilitation programs for
      disequilibrium, but only for the Dizziness Handicap Inventory (DHI) is an Italian
      translation available, validated on a small group of patients suffering from a
      peripheral acute vertigo. We translated and validated the reliability and
      validity of the DHI, the Situational Vertigo Questionnaire (SVQ), and the
      Activities-Specific Balance Confidence Scale (ABC) in 316 Italian patients
      complaining of dizziness due either to a peripheral or to a central vestibular
      deficit, or in whom vestibular signs were undetectable by means of instrumental
      testing or clinical evaluation. Cronbach's coefficient alpha, the homogeneity
      index, and test-retest reproducibility, confirmed reliability of the Italian
      version of the three questionnaires. Validity was confirmed by correlation test
      between questionnaire scores. Correlations with clinical variables suggested that
      they can be used as a complementary tool for the assessment of vestibular
      symptoms. In conclusion, the Italian versions of DHI, SVQ, and ABC are reliable
      and valid questionnaires for assessing the impact of dizziness on the quality of
      life of Italian patients with peripheral or central vestibular deficit.

PMID- 29067001
TI  - Culture in Glucose-Depleted Medium Supplemented with Fatty Acid and 3,3',5
      Triiodo-l-Thyronine Facilitates Purification and Maturation of Human Pluripotent
      Stem Cell-Derived Cardiomyocytes.
AB  - With recent advances in stem cell technology, it is becoming efficient to
      differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes, which can
      subsequently be used for myriad purposes, ranging from interrogating mechanisms
      of cardiovascular disease, developing novel cellular therapeutic approaches, as
      well as assessing the cardiac safety profile of compounds. However, the relative
      inability to acquire abundant pure and mature cardiomyocytes still hinders these
      applications. Recently, it was reported that glucose-depleted culture medium
      supplemented with lactate can facilitate purification of hPSC-derived
      cardiomyocytes. Here, we report that fatty acid as a lactate replacement has not
      only a similar purification effect but also improves the electrophysiological
      characteristics of hPSC-derived cardiomyocytes. Glucose-depleted culture medium
      supplemented with fatty acid and 3,3',5-Triiodo-l-thyronine (T3) was used during
      enrichment of hPSC-derived cardiomyocytes. Compared to untreated control cells,
      the treated cardiomyocytes exhibited enhanced action potential (AP) maximum
      upstroke velocity (as shown by a significant increase in dV/dtmax), action
      potential amplitude, as well as AP duration at 50% (APD50) and 90% (APD90) of
      repolarization. The treated cardiomyocytes displayed higher sensitivity to
      isoproterenol, more organized sarcomeric structures, and lower proliferative
      activity. Expression profiling showed that various ion channel and cardiac
      specific genes were elevated as well. Our results suggest that the use of fatty
      acid and T3 can facilitate purification and maturation of hPSC-derived
      cardiomyocytes.

PMID- 29067000
TI  - Lateral Fluid Percussion Injury Impairs Hippocampal Synaptic Soluble N
      Ethylmaleimide Sensitive Factor Attachment Protein Receptor Complex Formation.
AB  - Traumatic brain injury (TBI) and the activation of secondary injury mechanisms
      have been linked to impaired cognitive function, which, as observed in TBI
      patients and animal models, can persist for months and years following the
      initial injury. Impairments in neurotransmission have been well documented in
      experimental models of TBI, but the mechanisms underlying this dysfunction are
      poorly understood. Formation of the soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) complex facilitates vesicular docking and
      neurotransmitter release in the synaptic cleft. Published studies highlight a
      direct link between reduced SNARE complex formation and impairments in
      neurotransmitter release. While alterations in the SNARE complex have been
      described following severe focal TBI, it is not known if deficits in SNARE
      complex formation manifest in a model with reduced severity. We hypothesized that
      lateral fluid percussion injury (lFPI) reduces the abundance of SNARE proteins,
      impairs SNARE complex formation, and contributes to impaired neurobehavioral
      function. To this end, rats were subjected to lFPI or sham injury and tested for
      acute motor performance and cognitive function at 3 weeks post-injury. lFPI
      resulted in motor impairment between 1 and 5 days post-injury. Spatial
      acquisition and spatial memory, as assessed by the Morris water maze, were
      significantly impaired at 3 weeks after lFPI. To examine the effect of lFPI on
      synaptic SNARE complex formation in the injured hippocampus, a separate cohort of
      rats was generated and brains processed to evaluate hippocampal synaptosomal
      enriched lysates at 1 week post-injury. lFPI resulted in a significant reduction
      in multiple monomeric SNARE proteins, including VAMP2, and alpha-synuclein, and
      SNARE complex abundance. The findings in this study are consistent with our
      previously published observations suggesting that impairments in hippocampal
      SNARE complex formation may contribute to neurobehavioral dysfunction associated
      with TBI.

PMID- 29067002
TI  - Bacterial Synergism in Lignocellulose Biomass Degradation - Complementary Roles
      of Degraders As Influenced by Complexity of the Carbon Source.
AB  - Lignocellulosic biomass (LCB) is an attractive source of carbon for the
      production of sugars and other chemicals. Due to its inherent complexity and
      heterogeneity, efficient biodegradation requires the actions of different types
      of hydrolytic enzymes. In nature, complex microbial communities that work
      efficiently and often synergistically accomplish degradation. Studying such
      synergisms in LCB degradation is fundamental for the establishment of an optimal
      biological degradation process. Here, we examine the wheat straw degradation
      potential of synthetic microbial consortia composed of bacteria and fungi. Growth
      of, and enzyme secretion by, monocultures of degrader strains were studied in
      aerobic cultures using wheat straw as the sole carbon and energy source. To
      investigate synergism, co-cultures were constructed from selected strains and
      their performance was tested in comparison with the respective monocultures. In
      monoculture, each organism - with a typical enzymatic profile - was found to
      mainly consume the cellulose part of the substrate. One strain, Flavobacterium
      ginsengisoli so9, displayed an extremely high degradation capacity, as measured
      by its secreted enzymes. Among 13 different co-cultures, five presented
      synergisms. These included four bacterial bicultures and one bacterial-fungal
      triculture. The highest level of synergism was found in a Citrobacter
      freundii/Sphingobacterium multivorum biculture, which revealed an 18.2-fold
      increase of the produced biomass. As compared to both monocultures, this
      bacterial pair showed significantly increased enzymatic activities, in particular
      of cellobiohydrolases, mannosidases, and xylosidases. Moreover, the synergism was
      unique to growth on wheat straw, as it was completely absent in glucose-grown
      bicultures. Spent supernatants of either of the two partners were found to
      stimulate the growth on wheat straw of the counterpart organism, in a directional
      manner. Thus, the basis of the LCB-specific synergism might lie in the specific
      release of compounds or agents by S. multivorum w15 that promote the activity of
      C. freundii so4 and vice versa.

PMID- 29067004
TI  - Editorial: About the Foodborne Pathogen Campylobacter.

PMID- 29067003
TI  - Two-Component Signal Transduction Systems of Pathogenic Bacteria As Targets for
      Antimicrobial Therapy: An Overview.
AB  - The bacterial communities in a wide range of environmental niches sense and
      respond to numerous external stimuli for their survival. Primarily, a source they
      require to follow up this communication is the two-component signal transduction
      system (TCS), which typically comprises a sensor Histidine kinase for receiving
      external input signals and a response regulator that conveys a proper change in
      the bacterial cell physiology. For numerous reasons, TCSs have ascended as
      convincing targets for antibacterial drug design. Several studies have shown that
      TCSs are essential for the coordinated expression of virulence factors and, in
      some cases, for bacterial viability and growth. It has also been reported that
      the expression of antibiotic resistance determinants may be regulated by some
      TCSs. In addition, as a mode of signal transduction, phosphorylation of histidine
      in bacteria differs from normal serine/threonine and tyrosine phosphorylation in
      higher eukaryotes. Several studies have shown the molecular mechanisms by which
      TCSs regulate virulence and antibiotic resistance in pathogenic bacteria. In this
      review, we list some of the characteristics of the bacterial TCSs and their
      involvement in virulence and antibiotic resistance. Furthermore, this review
      lists and discusses inhibitors that have been reported to target TCSs in
      pathogenic bacteria.

PMID- 29067006
TI  - A Multispecies Fungal Biofilm Approach to Enhance the Celluloyltic Efficiency of
      Membrane Reactors for Consolidated Bioprocessing of Plant Biomass.
AB  - The constraints and advantages in cellulolytic enzymes production by fungal
      biofilms for a consolidated bioconversion process were investigated during this
      study. The biofilm cultivations were carried out in reactors designed for
      consolidated bioprocessing Multispecies Biofilm Membrane reactors, (MBM) where an
      aerobic fungal biofilm produces the lignocellulolytic enzymes while a fermenting
      microorganism forms the fermentation product at anaerobic conditions. It was
      shown that although mycelial growth was limited in the MBM reactors compared to
      submerged cultivations, the secretion of cellulolytic enzymes per cell dry weight
      was higher. When Trichoderma reesei was used as the sole enzyme producer,
      cellobiose accumulated in the liquid medium as the result of the deficiency of
      beta-glucosidase in the fungal secretome. To enhance beta-glucosidase activity,
      T. reesei was co-cultivated with A. phoenicis which is a beta-glucosidase
      overproducer. The two fungi formed a multispecies biofilm which produced a
      balanced cellulolytic cocktail for the saccharification of plant biomass. The
      mixed biofilm reached a 2.5 fold increase in beta-glucosidase production,
      compared to the single T. reesei biofilm. The enzymatic systems of single and
      mixed biofilms were evaluated regarding their efficiency on cellulosic substrates
      degradation. Washed solids from steam pretreated beechwood, as well as
      microcrystalline cellulose were used as the substrates. The enzymatic system of
      the multispecies biofilm released four times more glucose than the enzymatic
      system of T. reesei alone from both substrates and hydrolyzed 78 and 60% of the
      cellulose content of washed solids from beechwood and microcrystalline cellulose,
      respectively.

PMID- 29067007
TI  - Insights into Microalga and Bacteria Interactions of Selected Phycosphere
      Biofilms Using Metagenomic, Transcriptomic, and Proteomic Approaches.
AB  - Microalga are of high relevance for the global carbon cycling and it is well
      known that they are associated with a microbiota. However, it remains unclear, if
      the associated microbiota, often found in phycosphere biofilms, is specific for
      the microalga strains and which role individual bacterial taxa play. Here we
      provide experimental evidence that Chlorella saccharophila, Scenedesmus
      quadricauda, and Micrasterias crux-melitensis, maintained in strain collections,
      are associated with unique and specific microbial populations. Deep metagenome
      sequencing, binning approaches, secretome analyses in combination with RNA-Seq
      data implied fundamental differences in the gene expression profiles of the
      microbiota associated with the different microalga. Our metatranscriptome
      analyses indicates that the transcriptionally most active bacteria with respect
      to key genes commonly involved in plant-microbe interactions in the Chlorella
      (Trebouxiophyceae) and Scenedesmus (Chlorophyceae) strains belong to the phylum
      of the alpha-Proteobacteria. In contrast, in the Micrasterias (Zygnematophyceae)
      phycosphere biofilm bacteria affiliated with the phylum of the Bacteroidetes
      showed the highest gene expression rates. We furthermore show that effector
      molecules known from plant-microbe interactions as inducers for the innate
      immunity are already of relevance at this evolutionary early plant-microbiome
      level.

PMID- 29067005
TI  - Characterization of Four Multidrug Resistance Plasmids Captured from the
      Sediments of an Urban Coastal Wetland.
AB  - Self-transmissible and mobilizable plasmids contribute to the emergence and
      spread of multidrug-resistant bacteria by enabling the horizontal transfer of
      acquired antibiotic resistance. The objective of this study was to capture and
      characterize self-transmissible and mobilizable resistance plasmids from a
      coastal wetland impacted by urban stormwater runoff and human wastewater during
      the rainy season. Four plasmids were captured, two self-transmissible and two
      mobilizable, using both mating and enrichment approaches. Plasmid genomes,
      sequenced with either Illumina or PacBio platforms, revealed representatives of
      incompatibility groups IncP-6, IncR, IncN3, and IncF. The plasmids ranged in size
      from 36 to 144 kb and encoded known resistance genes for most of the major
      classes of antibiotics used to treat Gram-negative infections (tetracyclines,
      sulfonamides, beta-lactams, fluoroquinolones, aminoglycosides, and amphenicols).
      The mobilizable IncP-6 plasmid pLNU-11 was discovered in a strain of Citrobacter
      freundii enriched from the wetland sediments with tetracycline and nalidixic
      acid, and encodes a novel AmpC-like beta-lactamase (blaWDC-1), which shares less
      than 62% amino acid sequence identity with the PDC class of beta-lactamases found
      in Pseudomonas aeruginosa. Although the IncR plasmid pTRE-1611 was captured by
      mating wetland bacteria with P. putida KT2440 as recipient, it was found to be
      mobilizable rather than self-transmissible. Two self-transmissible multidrug
      resistance plasmids were also captured: the small (48 kb) IncN3 plasmid pTRE-131
      was captured by mating wetland bacteria with Escherichia coli HY842 where it is
      seemed to be maintained at nearly 240 copies per cell, while the large (144 kb)
      IncF plasmid pTRE-2011, which was isolated from a cefotaxime-resistant
      environmental strain of E. coli ST744, exists at just a single copy per cell.
      Furthermore, pTRE-2011 bears the globally epidemic blaCTX-M-55 extended-spectrum
      beta-lactamase downstream of ISEcp1. Our results indicate that urban coastal
      wetlands are reservoirs of diverse self-transmissible and mobilizable plasmids of
      relevance to human health.

PMID- 29067008
TI  - Diversity and Transmission of Gut Bacteria in Atta and Acromyrmex Leaf-Cutting
      Ants during Development.
AB  - The social Hymenoptera have distinct larval and adult stages separated by
      metamorphosis, which implies striking remodeling of external and internal body
      structures during the pupal stage. This imposes challenges to gut symbionts as
      existing cultures are lost and may or may not need to be replaced. To elucidate
      the extent to which metamorphosis interrupts associations between bacteria and
      hosts, we analyzed changes in gut microbiota during development and traced the
      transmission routes of dominant symbionts from the egg to adult stage in the leaf
      cutting ants Acromyrmex echinatior and Atta cephalotes, which are both important
      functional herbivores in the New World tropics. Bacterial density remained
      similar across the developmental stages of Acromyrmex, but Atta brood had very
      low bacterial prevalences suggesting that bacterial gut symbionts are not
      actively maintained. We found that Wolbachia was the absolute dominant bacterial
      species across developmental stages in Acromyrmex and we confirmed that Atta
      lacks Wolbachia also in the immature stages, and had mostly Mollicutes bacteria
      in the adult worker guts. Wolbachia in Acromyrmex appeared to be transovarially
      transmitted similar to transmission in solitary insects. In contrast, Mollicutes
      were socially transmitted from old workers to newly emerged callows. We found
      that larval and pupal guts of both ant species contained Pseudomonas and
      Enterobacter bacteria that are also found in fungus gardens, but hardly or not in
      adult workers, suggesting they are beneficial only for larval growth and
      development. Our results reveal that transmission pathways for bacterial
      symbionts may be very different both between developmental stages and between
      sister genera and that identifying the mechanisms of bacterial acquisition and
      loss will be important to clarify their putative mutualistic functions.

PMID- 29067009
TI  - An Investigation into Rumen Fungal and Protozoal Diversity in Three Rumen
      Fractions, during High-Fiber or Grain-Induced Sub-Acute Ruminal Acidosis
      Conditions, with or without Active Dry Yeast Supplementation.
AB  - Sub-acute ruminal acidosis (SARA) is a gastrointestinal functional disorder in
      livestock characterized by low rumen pH, which reduces rumen function, microbial
      diversity, host performance, and host immune function. Dietary management is used
      to prevent SARA, often with yeast supplementation as a pH buffer. Almost nothing
      is known about the effect of SARA or yeast supplementation on ruminal protozoal
      and fungal diversity, despite their roles in fiber degradation. Dairy cows were
      switched from a high-fiber to high-grain diet abruptly to induce SARA, with and
      without active dry yeast (ADY, Saccharomyces cerevisiae) supplementation, and
      sampled from the rumen fluid, solids, and epimural fractions to determine
      microbial diversity using the protozoal 18S rRNA and the fungal ITS1 genes via
      Illumina MiSeq sequencing. Diet-induced SARA dramatically increased the number
      and abundance of rare fungal taxa, even in fluid fractions where total reads were
      very low, and reduced protozoal diversity. SARA selected for more lactic-acid
      utilizing taxa, and fewer fiber-degrading taxa. ADY treatment increased fungal
      richness (OTUs) but not diversity (Inverse Simpson, Shannon), but increased
      protozoal richness and diversity in some fractions. ADY treatment itself
      significantly (P < 0.05) affected the abundance of numerous fungal genera as seen
      in the high-fiber diet: Lewia, Neocallimastix, and Phoma were increased, while
      Alternaria, Candida Orpinomyces, and Piromyces spp. were decreased. Likewise, for
      protozoa, ADY itself increased Isotricha intestinalis but decreased Entodinium
      furca spp. Multivariate analyses showed diet type was most significant in driving
      diversity, followed by yeast treatment, for AMOVA, ANOSIM, and weighted UniFrac.
      Diet, ADY, and location were all significant factors for fungi (PERMANOVA, P =
      0.0001, P = 0.0452, P = 0.0068, Monte Carlo correction, respectively, and
      location was a significant factor (P = 0.001, Monte Carlo correction) for
      protozoa. Diet-induced SARA shifts diversity of rumen fungi and protozoa and
      selects against fiber-degrading species. Supplementation with ADY mitigated this
      reduction in protozoa, presumptively by triggering microbial diversity shifts (as
      seen even in the high-fiber diet) that resulted in pH stabilization. ADY did not
      recover the initial community structure that was seen in pre-SARA conditions.

PMID- 29067010
TI  - Nitric Oxide Accumulation: The Evolutionary Trigger for Phytopathogenesis.
AB  - Many publications highlight the importance of nitric oxide (NO) in plant-bacteria
      interactions, either in the promotion of health and plant growth or in
      pathogenesis. However, the role of NO in the signaling between bacteria and
      plants and in the fate of their interaction, as well as the reconstruction of
      their interactive evolution, remains largely unknown. Despite the complexity of
      the evolution of life on Earth, we explore the hypothesis that denitrification
      and aerobic respiration were responsible for local NO accumulation, which
      triggered primordial antagonistic biotic interactions, namely the first
      phytopathogenic interactions. N-oxides, including NO, could globally accumulate
      via lightning synthesis in the early anoxic ocean and constitute pools for the
      evolution of denitrification, considered an early step of the biological nitrogen
      cycle. Interestingly, a common evolution may be proposed for components of
      denitrification and aerobic respiration pathways, namely for NO and oxygen
      reductases, a theory compatible with the presence of low amounts of oxygen before
      the great oxygenation event (GOE), which was generated by Cyanobacteria. During
      GOE, the increase in oxygen caused the decrease of Earth's temperature and the
      consequent increase of oxygen dissolution and availability, making aerobic
      respiration an increasingly dominant trait of the expanding mesophilic lifestyle.
      Horizontal gene transfer was certainly important in the joint expansion of
      mesophily and aerobic respiration. First denitrification steps lead to NO
      formation through nitrite reductase activity, and NO may further accumulate when
      oxygen binds NO reductase, resulting in denitrification blockage. The consequent
      transient NO surplus in an oxic niche could have been a key factor for a
      successful outcome of an early denitrifying prokaryote able to scavenge oxygen by
      NO/oxygen reductase or by an independent heterotrophic aerobic respiration
      pathway. In fact, NO surplus could result in toxicity causing "the first disease"
      in oxygen-producing Cyanobacteria. We inspected in bacteria the presence of
      sequences similar to the NO-producing nitrite reductase nirS gene of Thermus
      thermophilus, an extreme thermophilic aerobe of the Thermus/Deinococcus group,
      which constitutes an ancient lineage related to Cyanobacteria. In silico analysis
      revealed the relationship between the presence of nirS genes and
      phytopathogenicity in Gram-negative bacteria.

PMID- 29067011
TI  - Aii810, a Novel Cold-Adapted N-Acylhomoserine Lactonase Discovered in a
      Metagenome, Can Strongly Attenuate Pseudomonas aeruginosa Virulence Factors and
      Biofilm Formation.
AB  - The pathogen Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence
      and biofilm formation. Enzymatic disruption of quorum sensing is a promising anti
      infection therapeutic strategy that does not rely on antibiotics. Here, a novel
      gene (aii810) encoding an N-acylhomoserine lactonase was isolated from the Mao
      tofu metagenome for the first time. Aii810 encoded a protein of 269 amino acids
      and was expressed in Escherichia coli BL21 (DE3) in soluble form. It showed the
      highest activity at 20 degrees C, and it maintained 76.5% of activity at 0
      degrees C and more than 50% activity at 0-40 degrees C. The optimal pH was 8.0.
      It was stable in both neutral and slightly alkaline conditions and at
      temperatures below 40 degrees C. The enzyme hydrolyzed several rho-nitrophenyl
      esters, but its best substrate was rho-nitrophenyl acetate. Its kcat and Km
      values were 347.7 S-1 and 205.1 MUM, respectively. It efficiently degraded N
      butyryl-L-homoserine lactone and N-(3-oxododecanoyl)-L-homoserine lactone,
      exceeding hydrolysis rates of 72.3 and 100%, respectively. Moreover, Aii810
      strongly attenuated P. aeruginosa virulence and biofilm formation. This enzyme
      with high anti-QS activity was the most cold-adapted N-acylhomoserine lactonase
      reported, which makes it an attractive enzyme for use as a therapeutic agent
      against P. aeruginosa infection.

PMID- 29067013
TI  - Methodological Considerations and Comparisons of Measurement Results for
      Extracellular Proteolytic Enzyme Activities in Seawater.
AB  - Microbial extracellular hydrolytic enzymes that degrade organic matter in aquatic
      ecosystems play key roles in the biogeochemical carbon cycle. To provide linkages
      between hydrolytic enzyme activities and genomic or metabolomic studies in
      aquatic environments, reliable measurements are required for many samples at one
      time. Extracellular proteases are one of the most important classes of enzymes in
      aquatic microbial ecosystems, and protease activities in seawater are commonly
      measured using fluorogenic model substrates. Here, we examined several concerns
      for measurements of extracellular protease activities (aminopeptidases, and
      trypsin-type, and chymotrypsin-type activities) in seawater. Using a fluorometric
      microplate reader with low protein binding, 96-well microplates produced reliable
      enzymatic activity readings, while use of regular polystyrene microplates
      produced readings that showed significant underestimation, especially for trypsin
      type proteases. From the results of kinetic experiments, this underestimation was
      thought to be attributable to the adsorption of both enzymes and substrates onto
      the microplate. We also examined solvent type and concentration in the working
      solution of oligopeptide-analog fluorogenic substrates using dimethyl sulfoxide
      (DMSO) and 2-methoxyethanol (MTXE). The results showed that both 2% (final
      concentration of solvent in the mixture of seawater sample and substrate working
      solution) DMSO and 2% MTXE provide similarly reliable data for most of the tested
      substrates, except for some substrates which did not dissolve completely in these
      assay conditions. Sample containers are also important to maintain the level of
      enzyme activity in natural seawater samples. In a small polypropylene containers
      (e.g., standard 50-mL centrifugal tube), protease activities in seawater sample
      rapidly decreased, and it caused underestimation of natural activities,
      especially for trypsin-type and chymotrypsin-type proteases. In conclusion, the
      materials and method for measurements should be carefully selected in order to
      accurately determine the activities of microbial extracellular hydrolytic enzymes
      in aquatic ecosystems; especially, low protein binding materials should be chosen
      to use at overall processes of the measurement.

PMID- 29067012
TI  - Nitrogen Loss from Pristine Carbonate-Rock Aquifers of the Hainich Critical Zone
      Exploratory (Germany) Is Primarily Driven by Chemolithoautotrophic Anammox
      Processes.
AB  - Despite the high relevance of anaerobic ammonium oxidation (anammox) for nitrogen
      loss from marine systems, its relative importance compared to denitrification has
      less been studied in freshwater ecosystems, and our knowledge is especially
      scarce for groundwater. Surprisingly, phospholipid fatty acids (PLFA)-based
      studies identified zones with potentially active anammox bacteria within two
      superimposed pristine limestone aquifer assemblages of the Hainich Critical Zone
      Exploratory (CZE; Germany). We found anammox to contribute an estimated 83% to
      total nitrogen loss in suboxic groundwaters of these aquifer assemblages at rates
      of 3.5-4.7 nmol L-1 d-1, presumably favored over denitrification by low organic
      carbon availability. Transcript abundances of hzsA genes encoding hydrazine
      synthase exceeded nirS and nirK transcript abundances encoding denitrifier
      nitrite reductase by up to two orders of magnitude, providing further support of
      a predominance of anammox. Anammox bacteria, dominated by groups closely related
      to Cand. Brocadia fulgida, constituted up to 10.6% of the groundwater microbial
      community and were ubiquitously present across the two aquifer assemblages with
      indication of active anammox bacteria even in the presence of 103 MUmol L-1
      oxygen. Co-occurrence of hzsA and amoA gene transcripts encoding ammonia mono
      oxygenase suggested coupling between aerobic and anaerobic ammonium oxidation
      under suboxic conditions. These results clearly demonstrate the relevance of
      anammox as a key process driving nitrogen loss from oligotrophic groundwater
      environments, which might further be enhanced through coupling with incomplete
      nitrification.

PMID- 29067014
TI  - A Novel MFS Transporter Gene ChMfs1 Is Important for Hyphal Morphology,
      Conidiation, and Pathogenicity in Colletotrichum higginsianum.
AB  - Colletotrichum higginsianum is a widely distributed fungus attacking many
      cruciferous species. To investigate pathogenic mechanisms of the pathogen on the
      host Arabidopsis thaliana, we screened and obtained a virulence-deficient mutant
      Ch-1-T513 in a T-DNA insertion mutant library of C. higginsianum. The mutant Ch-1
      T513 produced yellow colony centers with distorted multi-branching hyphal tips as
      well as producing few conidia. Heavily swollen hyphae in the mutant could be
      observed, and intra-hyphal hyphae were found to be formed in the balloon-shaped
      hyphae. The mutant failed to produce lesions on 12-day-old Arabidopsis seedlings,
      and invasive hyphae did not differentiate into large primary and thin secondary
      hyphae after appressorial formation on Arabidopsis leaves, but formed abundant
      bulbous hyphae in epidermal cells. Southern blot analysis showed Ch-1-T513 had
      double-site T-DNA integrations. The mutant had insertions upstream of genes for a
      major facilitator superfamily (MFS) transporter, ChMfs1 and an aldo/keto
      reductase, ChAkr. Complementation experiments by transforming genomic sequences
      from a wild-type strain into the insertion mutant demonstrated that ChMfs1 is
      involved in the Ch-1-T513 phenotype. The complementation strain C-ChMfs1-1
      exhibited normal hyphal morphology, conidiation, and pathogenicity identical to
      the wild-type. The results demonstrate that ChMfs1 is involved in intra-hyphal
      hyphae production, conidiation, and pathogenicity in C. higginsianum. To our
      knowledge, this is the first report of a MFS transporter gene in a
      phytopathogenic fungus associated with intra-hyphal hyphae formation, playing a
      key role in infection of its plant host.

PMID- 29067016
TI  - Pivotal Impacts of Retrotransposon Based Invasive RNAs on Evolution.
AB  - RNAs have long been described as the mediators of gene expression; they play a
      vital role in the structure and function of cellular complexes. Although the role
      of RNAs in the prokaryotes is mainly confined to these basic functions, the
      effects of these molecules in regulating the gene expression and enzymatic
      activities have been discovered in eukaryotes. Recently, a high-resolution
      analysis of the DNA obtained from different organisms has revealed a fundamental
      impact of the RNAs in shaping the genomes, heterochromatin formation, and gene
      creation. Deep sequencing of the human genome revealed that about half of our DNA
      is comprised of repetitive sequences (remnants of transposable element movements)
      expanded mostly through RNA-mediated processes. ORF2 encoded by L1
      retrotransposons is a cellular reverse transcriptase which is mainly responsible
      for RNA invasion of various transposable elements (L1s, Alus, and SVAs) and
      cellular mRNAs in to the genomic DNA. In addition to increasing retroelements
      copy number; genomic expansion in association with centromere, telomere, and
      heterochromatin formation as well as pseudogene creation are the evolutionary
      consequences of this RNA-based activity. Threatening DNA integrity by disrupting
      the genes and forming excessive double strand breaks is another effect of this
      invasion. Therefore, repressive mechanisms have been evolved to control the
      activities of these invasive intracellular RNAs. All these mechanisms now have
      essential roles in the complex cellular functions. Therefore, it can be concluded
      that without direct action of RNA networks in shaping the genome and in the
      development of different cellular mechanisms, the evolution of higher eukaryotes
      would not be possible.

PMID- 29067015
TI  - Serum Metabolic Alterations upon Zika Infection.
AB  - Zika virus (ZIKV) infection has recently emerged as a major concern worldwide due
      to its strong association with nervous system malformation (microcephaly) of
      fetuses in pregnant women infected by the virus. Signs and symptoms of ZIKV
      infection are often mistaken with other common viral infections. Since
      transmission may occur through biological fluids exchange and coitus, in addition
      to mosquito bite, this condition is an important infectious disease. Thus,
      understanding the mechanism of viral infection has become an important research
      focus, as well as providing potential targets for assertive clinical diagnosis
      and quality screening for hemoderivatives. Within this context, the present work
      analyzed blood plasma from 79 subjects, divided as a control group and a ZIKV
      infected group. Samples underwent direct-infusion mass spectrometry and
      statistical analysis, where eight markers related to the pathophysiological
      process of ZIKV infection were elected and characterized. Among these,
      Angiotensin (1-7) and Angiotensin I were upregulated under infection, showing an
      attempt to induce autophagy of the infected cells. However, this finding is
      concerning about hypertensive individuals under treatment with inhibitors of the
      Renin-Angiotensin System (RAS), which could reduce this response against the
      virus and exacerbate the symptoms of the infection. Moreover, one of the most
      abundant glycosphingolipids in the nervous tissue, Ganglioside GM2, was also
      elected in the present study as an infection biomarker. Considered an important
      pathogen receptor at membrane's outer layer, this finding represents the
      importance of gangliosides for ZIKV infection and its association with brain
      tropism. Furthermore, a series of phosphatidylinositols were also identified as
      biomarkers, implying a significant role of the PI3K-AKT-mTOR Pathway in this
      mechanism. Finally, these pathways may also be understood as potential targets to
      be considered in pharmacological intervention studies on ZIKV infection
      management.

PMID- 29067018
TI  - Molecular Characterization of Novel Totivirus-Like Double-Stranded RNAs from
      Puccinia striiformis f. sp. tritici, the Causal Agent of Wheat Stripe Rust.
AB  - Characterization of newly isolated mycoviruses may contribute to understanding of
      the evolution and diversity of viruses. Here, a deep sequencing approach was used
      to analyze the double-stranded RNA (dsRNA) mycoviruses isolated from field
      collected P. striiformis samples in China. Database searches showed the presence
      of at least four totivirus-like sequences, termed Puccinia striiformis virus 1 to
      4 (PsV1 to 4). All of these identified sequences contained two overlapping open
      reading frames (ORFs) which encode a putative coat protein (CP) and an RNA
      dependent RNA polymerase (RdRp) showing similar structures to members of the
      genus Totivirus. Each PsV contained a -1 ribosomal frameshifting region with a
      slippery site and a pseudoknot structure in the overlapped regions of these ORFs,
      indicating that the RdRp is translated as a CP-RdRp fusion. Phylogenetic analyses
      based on RdRp and CP suggested that these novel viruses belong to the genus
      Totivirus in the family Totiviridae. The presences of these PsVs were further
      validated by transmission electron microscope (TEM) and RT-PCR. Taken together,
      our results demonstrate the presence of diverse, novel totiviruses in the P.
      striiformis field populations.

PMID- 29067017
TI  - Identification of 2-Cys Peroxiredoxin (BmTPx-2) as Antioxidant Active Molecule
      from Babesia microti.
AB  - Peroxiredoxins (Prxs) are a family of antioxidant enzymes that reduce peroxides
      in the presence of thioredoxin, thioredoxin reductase, and nicotinamide adenine
      dinucleotide phosphate (NADPH) to resist oxidative stress. In this study, we
      identified and isolated a 2-Cys Prx designated as 'BmTPx-2' from Babesia microti,
      with a full-length cDNA of 826 bp and an open reading frame of 756 bp, which
      encodes a 251-amino acid protein. BLAST analysis demonstrated that BmTPx-2 shows
      the typical features of members of the 2-Cys Prx family, which includes harboring
      two conserved VCP motifs with Cys101 and Cys221 conserved cysteine residues.
      Recombinant BmTPx-2 was expressed in Escherichia coli and analyzed by western
      blot. The antioxidant activity of BmTPx-2 was demonstrated using a mixed-function
      oxidation system and oxidation of NADPH. Furthermore, BmTPx-2 mRNA expression
      level in parasites at the erythrocytes and tick stages were analyzed by real-time
      fluorescence quantitative PCR. Peak BmTPx-2 mRNA transcription was detected 8
      days after infection at the erythrocyte stage, but not at the tick stage. Taken
      together, this study characterized BmTPx-2 from B. microti as an antioxidant
      molecule that was specifically transcribed at the erythrocyte stage.

PMID- 29067019
TI  - Porcine Models of Biofilm Infections with Focus on Pathomorphology.
AB  - Bacterial biofilm formation is one of the main reasons for a negative treatment
      outcome and a high recurrence rate for many chronic infections in humans. The
      optimal way to study both the biofilm forming bacteria and the host response
      simultaneously is by using discriminative, reliable, and reproducible animal
      models of the infections. In this review, the advantages of in vivo studies are
      compared to in vitro studies of biofilm formation in infectious diseases. The pig
      is the animal of choice when developing and applying large animal models of
      infectious diseases due to its similarity of anatomy, physiology, and immune
      system to humans. Furthermore, conventional pigs spontaneously develop many of
      the same chronic bacterial infections as seen in humans. Therefore, in this
      review porcine models of five different infectious diseases all associated with
      biofilm formation and chronicity in humans are described. The infectious diseases
      are: chronic wounds, endocarditis, pyelonephritis, hematogenous osteomyelitis,
      and implant-associated osteomyelitis (IAO).

PMID- 29067020
TI  - Inheritance and Establishment of Gut Microbiota in Chickens.
AB  - In mammals, the microbiota can be transmitted from the placenta, uterus, and
      vagina of the mother to the infant. Unlike mammals, development of the avian
      embryo is a process isolated from the mother and thus in the avian embryo the gut
      microbial developmental process remains elusive. To explore the establishment and
      inheritance of the gut microbiome in the avian embryo, we used the chicken as the
      model organism to investigate the gut microbial composition in embryos, chicks,
      and maternal hens. We observed: (1) 28 phyla and 162 genera of microbes in
      embryos where the dominated genus was Halomonas (79%). (2) 65 genera were core
      microbiota in all stages with 42% and 62% gut microbial genera of embryo were
      found in maternal hen and chick, respectively. There was a moderate correlation
      (0.40) between the embryo and maternal, and 0.52 between the embryo and chick at
      the family level. (3) Gut microbes that are involved in substance metabolism,
      infectious disease, and environmental adaptation are enriched in embryos, chicks,
      and maternal hens, respectively. (4) 94% genera of gut microbial composition were
      similar among three different chicken breeds which were maintained under similar
      conditions. Our findings provide evidence to support the hypothesis that part of
      the microbial colonizers harbored in early embryos were inherited from maternal
      hens, and the gut microbial abundance and diversity were influenced by
      environmental factors and host genetic variation during development.

PMID- 29067021
TI  - Comparative Genomics of Facultative Bacterial Symbionts Isolated from European
      Orius Species Reveals an Ancestral Symbiotic Association.
AB  - Pest control in agriculture employs diverse strategies, among which the use of
      predatory insects has steadily increased. The use of several species within the
      genus Orius in pest control is widely spread, particularly in Mediterranean
      Europe. Commercial mass rearing of predatory insects is costly, and research
      efforts have concentrated on diet manipulation and selective breeding to reduce
      costs and improve efficacy. The characterisation and contribution of microbial
      symbionts to Orius sp. fitness, behaviour, and potential impact on human health
      has been neglected. This paper provides the first genome sequence level
      description of the predominant culturable facultative bacterial symbionts
      associated with five Orius species (O. laevigatus, O. niger, O. pallidicornis, O.
      majusculus, and O. albidipennis) from several geographical locations. Two types
      of symbionts were broadly classified as members of the genera Serratia and
      Leucobacter, while a third constitutes a new genus within the Erwiniaceae. These
      symbionts were found to colonise all the insect specimens tested, which evidenced
      an ancestral symbiotic association between these bacteria and the genus Orius.
      Pangenome analyses of the Serratia sp. isolates offered clues linking Type VI
      secretion system effector-immunity proteins from the Tai4 sub-family to the
      symbiotic lifestyle.

PMID- 29067022
TI  - Soil Viral Communities Vary Temporally and along a Land Use Transect as Revealed
      by Virus-Like Particle Counting and a Modified Community Fingerprinting Approach
      (fRAPD).
AB  - Environmental surveys on soil viruses are still rare and mostly anecdotal, i. e.,
      they mostly report on viruses at one location or for only a few sampling dates.
      Detailed time-series analysis with multiple samples can reveal the spatio
      temporal dynamics of viral communities and provide important input as to how
      viruses interact with their potential hosts and the environment. Such surveys,
      however, require fast, easy-to-apply and reliable methods. In the present study
      we surveyed monthly across 13 months the abundance of virus-like particles (VLP)
      and the structure of the viral communities in soils along a land use transect
      (i.e., forest, pasture, and cropland). We evaluated 32 procedures to extract VLP
      from soil using different buffers and mechanical methods. The most efficient
      extraction was achieved with 1* saline magnesium buffer in combination with 20
      min vortexing. For community structure analysis we developed an optimized
      fingerprinting approach (fluorescent RAPD-PCR; fRAPD) by combining RAPD-PCR with
      fluorescently labeled primers in order to size the obtained fragments on a
      capillary sequencing machine. With the concomitantly collected data of soil
      specific factors and weather data, we were able to find correlations of viral
      abundance and community structure with environmental variables and sampling site.
      More specifically, we found that soil specific factors such as pH and total
      nitrogen content played a significant role in shaping both soil viral abundance
      and community structure. The fRAPD analysis revealed high temporal changes and
      clustered the viral communities according to sampling sites. In particular we
      observed that temperature and rainfall shaped soil viral communities in non
      forest sites. In summary our findings suggest that sampling site was a key factor
      for shaping the abundance and community structure of soil viruses, and when site
      vegetation was reduced, temperature and rainfall were also important factors.

PMID- 29067023
TI  - Selection of Shared and Neoantigen-Reactive T Cells for Adoptive Cell Therapy
      Based on CD137 Separation.
AB  - Adoptive cell therapy (ACT) of autologous tumor infiltrating lymphocytes (TIL) is
      an effective immunotherapy for patients with solid tumors, yielding objective
      response rates of around 40% in refractory patients with metastatic melanoma.
      Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue
      for ex vivo expansion and infusion. Only a minor fraction of the administered T
      cells recognizes tumor antigens, such as shared and mutation-derived neoantigens,
      and consequently eliminates the tumor. Thus, there are many ongoing effects to
      identify and select tumor-specific TIL for therapy; however, those approaches are
      very costly and require months, which is unreasonable for most metastatic
      patients. CD137 (4-1BB) has been identified as a co-stimulatory marker, which is
      induced upon the specific interaction of T cells with their target cell.
      Therefore, CD137 can be a useful biomarker and an important tool for the
      selection of tumor-reactive T cells. Here, we developed and validated a simple
      and time efficient method for the selection of CD137-expressing T cells for
      therapy based on magnetic bead separation. CD137 selection was performed with
      clinical grade compliant reagents, and TIL were expanded in a large-scale manner
      to meet cell numbers required for the patient setting in a GMP facility. For the
      first time, the methodology was designed to comply with both clinical needs and
      limitations, and its feasibility was assessed. CD137-selected TIL demonstrated
      significantly increased antitumor reactivity and were enriched for T cells
      recognizing neoantigens as well as shared tumor antigens. CD137-based selection
      enabled the enrichment of tumor-reactive T cells without the necessity of knowing
      the epitope specificity or the antigen type. The direct implementation of the
      CD137 separation method to the cell production of TIL may provide a simple way to
      improve the clinical efficiency of TIL ACT.

PMID- 29067025
TI  - IL-4Ralpha Signaling in Keratinocytes and Early IL-4 Production Are Dispensable
      for Generating a Curative T Helper 1 Response in Leishmania major-Infected
      C57BL/6 Mice.
AB  - Experimental infection with the protozoan parasite Leishmania major has been
      extensively used to understand the mechanisms involved in T helper cell
      differentiation. Following infection, C57BL/6 mice develop a small self-healing
      cutaneous lesion and they are able to control parasite burden, a process linked
      to the development of T helper (Th) 1 cells. The local presence of IL-12 has been
      reported to be critical in driving Th1 cell differentiation. In addition, the
      early secretion of IL-4 was reported to potentially contribute to Th1 cell
      differentiation. Following infection with L. major, early keratinocyte-derived IL
      4 was suggested to contribute to Th1 cell differentiation. To investigate a
      putative autocrine role of IL-4 signaling on keratinocytes at the site of
      infection, we generated C57BL/6 mice deficient for IL-4Ralpha expression
      selectively in keratinocytes. Upon infection with L. major, these mice could
      control their inflammatory lesion and parasite load correlating with the
      development of Th1 effector cells. These data demonstrate that IL-4 signaling on
      keratinocytes does not contribute to Th1 cell differentiation. To further
      investigate the source of IL-4 in the skin during the first days after L. major
      infection, we used C57BL/6 IL-4 reporter mice allowing the visualization of IL-4
      mRNA expression and protein production. These mice were infected with L. major.
      During the first 3 days after infection, skin IL-4 mRNA expression was observed
      selectively in mast cells. However, no IL-4 protein production was detectable
      locally. In addition, early IL-4 blockade locally had no impact on subsequent Th1
      cell differentiation and control of the disease. Taken together, the present data
      rule out a major role for skin IL-4 and keratinocyte IL-4Ralpha signaling in the
      development of a Th1 protective immune response following experimental infection
      with L. major.

PMID- 29067026
TI  - Characterization of Rabbit Nucleotide-Binding Oligomerization Domain 1 (NOD1) and
      the Role of NOD1 Signaling Pathway during Bacterial Infection.
AB  - Nucleotide-binding oligomerization domain 1 (NOD1) is the most prominent of all
      NOD-like receptors, which in the mammalian innate immune system, serve as
      intracellular receptors for pathogens and endogenous molecules during tissue
      injury. From rabbit kidney cells, we cloned rabbit NOD1 (rNOD1) and identified an
      N-terminal caspase activation and recruitment domain, a central NACHT domain, and
      C-terminal leucine-rich repeat domains. rNOD1 was expressed in all tested
      tissues; infection with Escherichia coli induced significantly higher expression
      in the spleen, liver, and kidney compared to other tissues. The overexpression of
      rNOD1 induced the expression of proinflammatory cytokines Il1b, Il6, Il8, Ifn
      gamma, and Tnf and defensins, including Defb124, Defb125, Defb128, Defb135, and
      Np5 via activation of the nuclear factor (NF)-kappaB pathway. Overexpression of
      rNOD1 inhibited the growth of E. coli, whereas knockdown of rNOD1 or inhibition
      of the NF-kappaB pathway promoted the growth of E. coli. rNOD1 colocalized with
      LC3, upregulated autophagy pathway protein LC3-II, and increased autolysosome
      formation in RK-13 cells infected with E. coli. In summary, our results explain
      the primary signaling pathway and antibacterial ability of rNOD1, as well as the
      induction of autophagy that it mediates. Such findings suggest that NOD1 could
      contribute to therapeutic strategies such as targets of new vaccine adjuvants or
      drugs.

PMID- 29067027
TI  - Exoenzyme T Plays a Pivotal Role in the IFN-gamma Production after Pseudomonas
      Challenge in IL-12 Primed Natural Killer Cells.
AB  - Pseudomonas aeruginosa (PA) expresses the type III secretion system (T3SS) and
      effector exoenzymes that interfere with intracellular pathways. Natural killer
      (NK) cells play a key role in antibacterial immunity and their activation is
      highly dependent on IL-12 produced by myeloid cells. We studied PA and NK cell
      interactions and the role of IL-12 using human peripheral blood mononuclear
      cells, sorted human NK cells, and a human NK cell line (NK92). We used a wild
      type (WT) strain of PA (PAO1) or isogenic PA-deleted strains to delineate the
      role of T3SS and exoenzymes. Our hypotheses were tested in vivo in a PA-pneumonia
      mouse model. Human NK cells or NK92 cell line produced low levels of IFN-gamma in
      response to PA without IL-12 stimulation, whereas PA significantly increased IFN
      gamma after IL-12 priming. The modulation of IFN-gamma production by PA required
      bacteria-to-cell contact. Among T3SS effectors, exoenzyme T (ExoT) upregulates
      IFN-gamma production and control ERK activation. In vivo, ExoT also increases IFN
      gamma levels and the percentage of IFN-gamma+ NK cells in lungs during PA
      pneumonia, confirming in vitro data. In conclusion, our results suggest that T3SS
      could modulate the production of IFN-gamma by NK cells after PA infection through
      ERK activation.

PMID- 29067029
TI  - Unveiling the Identity of Wenwan Walnuts and Phylogenetic Relationships of Asian
      Juglans Species Using Restriction Site-Associated DNA-Sequencing.
AB  - Juglans species have considerable ecological and economic value worldwide. In
      China, Wenwan walnuts have been collected by aristocrats and noblemen for more
      than 2000 years. As a diversity center of Asian Juglans, five species are widely
      distributed in China. The most famous of these is Mahetao (J. hopeiensis), which
      is an uncharacterized species that is mostly cultivated. Wild J. hopeiensis
      individuals are very rare and are endemic to Hebei Province. Because of the
      minimal variations in previously used molecular markers and the heterogeneity
      between chloroplast and nuclear genomes, determining the phylogenetic
      relationships among the Juglans species has been challenging, and has hindered
      subsequent evolutionary inferences. In this study, we collected enough materials
      for both cultivated and wild Mahetao to construct well-resolved phylogenetic
      trees for Asian Juglans species. We used a high-throughput genome-wide
      restriction site-associated DNA sequencing method. Consequently, the identity of
      J. hopeiensis has been clearly resolved. Our results indicate that J. hopeiensis
      is a hybrid of J. regia and J. mandshurica. However, J. hopeiensis, J. regia and
      J. sigillata should be considered as a single species from section Juglans.
      Additionally, J. ailantifolia, J. cathayensis, and J. mandshurica likely
      represent one species from section Cardiocaryon according to morphological and
      molecular studies. These results are supported by population structure analysis
      and morphological comparison. We propose that J. hopeiensis trees growing in the
      wild should be conserved because of the economic value of their nuts. These trees
      may be of particular importance to impoverished communities. Furthermore, they
      may serve as a valuable genetic resource relevant for enhancing the production of
      edible walnuts. The 2b-RAD method is a viable option for future phylogenetic
      studies of Juglans species as well as other plant species.

PMID- 29067028
TI  - Sumoylation, Phosphorylation, and Acetylation Fine-Tune the Turnover of Plant
      Immunity Components Mediated by Ubiquitination.
AB  - Ubiquitination-mediated protein degradation plays a crucial role in the turnover
      of immune proteins through rapid alteration of protein levels. Specifically, the
      over-accumulation of immune proteins and consequent activation of immune
      responses in uninfected cells is prevented through degradation. Protein post
      translational modifications can influence and affect ubiquitination. There is
      accumulating evidence that suggests sumoylation, phosphorylation, and acetylation
      differentially affect the stability of immune-related proteins, so that control
      over the accumulation or degradation of proteins is fine-tuned. In this paper, we
      review the function and mechanism of sumoylation, phosphorylation, acetylation,
      and ubiquitination in plant disease resistance responses, focusing on how
      ubiquitination reacts with sumoylation, phosphorylation, and acetylation to
      regulate plant disease resistance signaling pathways. Future research directions
      are suggested in order to provide ideas for signaling pathway studies, and to
      advance the implementation of disease resistance proteins in economically
      important crops.

PMID- 29067030
TI  - Physical Location of New PCR-Based Markers and Powdery Mildew Resistance Gene(s)
      on Rye (Secale cereale L.) Chromosome 4 Using 4R Dissection Lines.
AB  - Rye (Secale cereale L.) 4R chromosome contains elite genes that are applicable
      for wheat (Triticum aestivum L.) cultivar improvement. PCR-based 4R-specific
      markers can benefit the detection of elite genes on 4R in wheat backgrounds. In
      this study, a new fluorescence in situ hybridization (FISH) map of the 4RKu
      chromosome of rye Kustro has been constructed. A set of 4RKu dissection lines was
      obtained and 301 new 4RKu-specific markers were developed using specific length
      amplified fragment sequencing (SLAF-seq) technology. These markers were combined
      with the 99 4RKu-specific markers previously developed, and were physically
      mapped to 4RKu chromosome using the new FISH map and the 4RKu dissection lines. A
      total of 338 of the 400 markers have been successfully mapped to six regions of
      4RKu chromosome. Additionally, the powdery mildew resistance gene(s) on the 4RLKu
      arm was located to the segment between L.4 and L.8, the same region where 115
      4RLKu-specific markers were mapped. The markers developed in this study can be
      used to identify a specific segment of 4R chromatin in wheat backgrounds, help
      construct a high-density physical map of 4R chromosome, and facilitate the
      utilization of elite genes on 4R chromosome in wheat breeding programs.

PMID- 29067024
TI  - Multifaceted Role of Neuropilins in the Immune System: Potential Targets for
      Immunotherapy.
AB  - Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed
      in all vertebrates and widely conserved across species. The two isoforms, such as
      neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class
      III Semaphorins and for members of the vascular endothelial growth factor family
      of molecules and are widely known for their role in a wide array of physiological
      processes, such as cardiovascular, neuronal development and patterning,
      angiogenesis, lymphangiogenesis, as well as various clinical disorders.
      Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in
      normal physiological as well as different pathological conditions, including
      cancer, immunological disorders, and bone diseases. However, little is known
      concerning the molecular pathways that govern these functions. In addition, NRP1
      expression has been characterized in different immune cellular phenotypes
      including macrophages, dendritic cells, and T cell subsets, especially regulatory
      T cell populations. By contrast, the functions of NRP2 in immune cells are less
      well known. In this review, we briefly summarize the genomic organization,
      structure, and binding partners of the NRPs and extensively discuss the recent
      advances in their role and function in different immune cell subsets and their
      clinical implications.

PMID- 29067031
TI  - Cytokinins and Abscisic Acid Act Antagonistically in the Regulation of the Bud
      Outgrowth Pattern by Light Intensity.
AB  - Bud outgrowth is a key process in the elaboration of yield and visual quality in
      rose crops. Although light intensity is well known to affect bud outgrowth,
      little is known on the mechanisms involved in this regulation. The objective of
      this work was to test if the control of bud outgrowth pattern along the stem by
      photosynthetic photon flux density (PPFD) is mediated by sugars, cytokinins
      and/or abscisic acid in intact rose plants. Rooted cuttings of Rosa hybrida
      'Radrazz' were grown in growth chambers under high PPFD (530 MUmol m-2 s-1) until
      the floral bud visible stage. Plants were then either placed under low PPFD (90
      MUmol m-2 s-1) or maintained under high PPFD. Bud outgrowth inhibition by low
      PPFD was associated with lower cytokinin and sugar contents and a higher abscisic
      acid content in the stem. Interestingly, cytokinin supply to the stem restored
      bud outgrowth under low PPFD. On the other hand, abscisic acid supply inhibited
      outgrowth under high PPFD and antagonized bud outgrowth stimulation by cytokinins
      under low PPFD. In contrast, application of sugars did not restore bud outgrowth
      under low PPFD. These results suggest that PPFD regulation of bud outgrowth in
      rose involves a signaling pathway in which cytokinins and abscisic acid play
      antagonistic roles. Sugars can act as nutritional and signaling compounds and may
      be involved too, but do not appear as the main regulator of the response to PPFD.

PMID- 29067032
TI  - Comparative UAV and Field Phenotyping to Assess Yield and Nitrogen Use Efficiency
      in Hybrid and Conventional Barley.
AB  - With the commercialization and increasing availability of Unmanned Aerial
      Vehicles (UAVs) multiple rotor copters have expanded rapidly in plant phenotyping
      studies with their ability to provide clear, high resolution images. As such, the
      traditional bottleneck of plant phenotyping has shifted from data collection to
      data processing. Fortunately, the necessarily controlled and repetitive design of
      plant phenotyping allows for the development of semi-automatic computer
      processing tools that may sufficiently reduce the time spent in data extraction.
      Here we present a comparison of UAV and field based high throughput plant
      phenotyping (HTPP) using the free, open-source image analysis software FIJI (Fiji
      is just ImageJ) using RGB (conventional digital cameras), multispectral and
      thermal aerial imagery in combination with a matching suite of ground sensors in
      a study of two hybrids and one conventional barely variety with ten different
      nitrogen treatments, combining different fertilization levels and application
      schedules. A detailed correlation network for physiological traits and
      exploration of the data comparing between treatments and varieties provided
      insights into crop performance under different management scenarios. Multivariate
      regression models explained 77.8, 71.6, and 82.7% of the variance in yield from
      aerial, ground, and combined data sets, respectively.

PMID- 29067033
TI  - Events Associated with Early Age-Related Decline in Adventitious Rooting
      Competence of Eucalyptus globulus Labill.
AB  - The development of adventitious roots is affected by several factors, including
      the age of the cutting donor plant, which negatively affects rooting capacity.
      Eucalyptus globulus quickly loses rooting capacity of cuttings as the donor plant
      ages, although the molecular and biochemical mechanisms behind this process are
      still unclear. To better understand the bases of rooting competence loss in E.
      globulus, the time required for a significant decline in rhizogenic ability
      without exogenous auxin was determined in microcuttings derived from donor plants
      of different ages after sowing. Tip cuttings of donor plants were severed before
      and after loss of rooting competence of microcuttings to test the hypothesis that
      auxin and carbohydrate homeostasis regulate rooting competence decline. There
      were no significant changes in concentration of carbohydrates, flavonoids, or
      proteins before and after the loss of rooting capacity. Peroxidase (EC 1.11.1.7)
      total activity increased with loss of rooting competence. Auxin concentration
      showed the opposite pattern. In good agreement, TAA1, a key gene in auxin
      biosynthesis, had lower expression after loss of rooting capacity. The same
      applied to the auxin receptor gene TIR1, suggesting reduced auxin sensitivity. On
      the other hand, genes associated with auxin response repression (TPL, IAA12) or
      with the action of cytokinins, the rhizogenesis inhibitor-related ARR1, showed
      higher expression in plants with lower rooting competence. Taken together, data
      suggest that age negatively affects E. globulus rooting by a combination of
      factors. Decreased endogenous auxin concentration, possibly caused by less
      biosynthesis, lower auxin sensitivity, higher expression of genes inhibiting
      auxin action, as well as of genes related to the action of cytokinins, appear to
      play roles in this process.

PMID- 29067034
TI  - Auxin Homeostasis in Arabidopsis Ovules Is Anther-Dependent at Maturation and
      Changes Dynamically upon Fertilization.
AB  - The plant hormone auxin is a vital component for plant reproduction as it
      regulates the development of both male and female reproductive organs, including
      ovules and gynoecia. Furthermore, auxin plays important roles in the development
      and growth of seeds and fruits. Auxin responses can be detected in ovules shortly
      after fertilization, and it has been suggested that this accumulation is a
      prerequisite for the developmental reprogramming of the ovules to seeds, and of
      the gynoecium to a fruit. However, the roles of auxin at the final stages of
      ovule development, and the sources of auxin leading to the observed responses in
      ovules after fertilization have remained elusive. Here we have characterized the
      auxin readout in Arabidopsis ovules, at the pre-anthesis, anthesis and in the
      immediate post-fertilization stages, using the R2D2 auxin sensor. In addition we
      have mapped the expression of auxin biosynthesis and conjugation genes, as well
      as that of auxin transporting proteins, during the same developmental stages.
      These analyses reveal specific spatiotemporal patterns of the different auxin
      homeostasis regulators. Auxin biosynthesis genes and auxin transport proteins
      define a pre-patterning of vascular cell identity in the pre-anthesis funiculus.
      Furthermore, our data suggests that auxin efflux from the ovule is restricted in
      an anther-dependent manner, presumably to synchronize reproductive organ
      development and thereby optimizing the chances of successful fertilization.
      Finally, de novo auxin biosynthesis together with reduced auxin conjugation and
      transport result in an enhanced auxin readout throughout the sporophytic tissues
      of the ovules soon after fertilization. Together, our results suggest a
      sophisticated set of regulatory cascades that allow successful fertilization and
      the subsequent transition of the female reproductive structures into seeds and
      fruits.

PMID- 29067035
TI  - Transcriptomics and Alternative Splicing Analyses Reveal Large Differences
      between Maize Lines B73 and Mo17 in Response to Aphid Rhopalosiphum padi
      Infestation.
AB  - Maize (Zea mays L.) is a staple crop worldwide with extensive genetic variations.
      Various insects attack maize plants causing large yield loss. Here, we
      investigated the responses of maize B73, a susceptible line, and Mo17, a
      resistant line, to the aphid Rhopalosiphum padi on metabolite and transcriptome
      levels. R. padi feeding had no effect on the levels of the defensive metabolites
      benzoxazinoids (Bxs) in either line, and Mo17 contained substantially greater
      levels of Bxs than did B73. Profiling of the differentially expressed genes
      revealed that B73 and Mo17 responded to R. padi infestation specifically, and
      importantly, these two lines showed large gene expression differences even
      without R. padi herbivory. Correlation analysis identified four transcription
      factors (TFs) that might account for the high Bx levels in Mo17. Similarly,
      genome-wide alternative splicing (AS) analyses indicated that both B73 and Mo17
      had temporally specific responses to R. padi infestation, and these two lines
      also exhibited large differences of AS regulation under normal condition, and 340
      genes, including 10 TFs, were constantly differentially spliced. This study
      provides large-scale resource datasets for further studies on the mechanisms
      underlying maize-aphid interactions, and highlights the phenotypic divergence in
      defense against aphids among maize varieties.

PMID- 29067036
TI  - Arbuscular Mycorrhizal Symbiosis Alleviates Salt Stress in Black Locust through
      Improved Photosynthesis, Water Status, and K+/Na+ Homeostasis.
AB  - Soil salinization and the associated land degradation are major and growing
      ecological problems. Excess salt in soil impedes plant photosynthetic processes
      and root uptake of water and nutrients such as K+. Arbuscular mycorrhizal (AM)
      fungi can mitigate salt stress in host plants. Although, numerous studies
      demonstrate that photosynthesis and water status are improved by mycorrhizae, the
      molecular mechanisms involved have received little research attention. In the
      present study, we analyzed the effects of AM symbiosis and salt stress on
      photosynthesis, water status, concentrations of Na+ and K+, and the expression of
      several genes associated with photosynthesis (RppsbA, RppsbD, RprbcL, and RprbcS)
      and genes coding for aquaporins or membrane transport proteins involved in K+
      and/or Na+ uptake, translocation, or compartmentalization homeostasis (RpSOS1,
      RpHKT1, RpNHX1, and RpSKOR) in black locust. The results showed that salinity
      reduced the net photosynthetic rate, stomatal conductance, and relative water
      content in both non-mycorrhizal (NM) and AM plants; the reductions of these three
      parameters were less in AM plants compared with NM plants. Under saline
      conditions, AM fungi significantly improved the net photosynthetic rate, quantum
      efficiency of photosystem II photochemistry, and K+ content in plants, but
      evidently reduced the Na+ content. AM plants also displayed a significant
      increase in the relative water content and an evident decrease in the shoot/root
      ratio of Na+ in the presence of 200 mM NaCl compared with NM plants.
      Additionally, mycorrhizal colonization upregulated the expression of three
      chloroplast genes (RppsbA, RppsbD, and RprbcL) in leaves, and three genes
      (RpSOS1, RpHKT1, and RpSKOR) encoding membrane transport proteins involved in
      K+/Na+ homeostasis in roots. Expression of several aquaporin genes was regulated
      by AM symbiosis in both leaves and roots depending on soil salinity. This study
      suggests that the beneficial effects of AM symbiosis on the photosynthetic
      capacity, water status, and K+/Na+ homeostasis lead to the improved growth
      performance and salt tolerance of black locust exposed to salt stress.

PMID- 29067037
TI  - X-FIDO: An Effective Application for Detecting Olive Quick Decline Syndrome with
      Deep Learning and Data Fusion.
AB  - We have developed a vision-based program to detect symptoms of Olive Quick
      Decline Syndrome (OQDS) on leaves of Olea europaea L. infected by Xylella
      fastidiosa, named X-FIDO (Xylella FastIdiosa Detector for O. europaea L.).
      Previous work predicted disease from leaf images with deep learning but required
      a vast amount of data which was obtained via crowd sourcing such as the
      PlantVillage project. This approach has limited applicability when samples need
      to be tested with traditional methods (i.e., PCR) to avoid incorrect training
      input or for quarantine pests which manipulation is restricted. In this paper, we
      demonstrate that transfer learning can be leveraged when it is not possible to
      collect thousands of new leaf images. Transfer learning is the re-application of
      an already trained deep learner to a new problem. We present a novel algorithm
      for fusing data at different levels of abstraction to improve performance of the
      system. The algorithm discovers low-level features from raw data to automatically
      detect veins and colors that lead to symptomatic leaves. The experiment included
      images of 100 healthy leaves, 99 X. fastidiosa-positive leaves and 100 X.
      fastidiosa-negative leaves with symptoms related to other stress factors (i.e.,
      abiotic factors such as water stress or others diseases). The program detects
      OQDS with a true positive rate of 98.60 +/- 1.47% in testing, showing great
      potential for image analysis for this disease. Results were obtained with a
      convolutional neural network trained with the stochastic gradient descent method,
      and ten trials with a 75/25 split of training and testing data. This work shows
      potential for massive screening of plants with reduced diagnosis time and cost.

PMID- 29067038
TI  - An Algorithm for Template-Based Prediction of Secondary Structures of Individual
      RNA Sequences.
AB  - While understanding the structure of RNA molecules is vital for deciphering their
      functions, determining RNA structures experimentally is exceptionally hard. At
      the same time, extant approaches to computational RNA structure prediction have
      limited applicability and reliability. In this paper we provide a method to solve
      a simpler yet still biologically relevant problem: prediction of secondary RNA
      structure using structure of different molecules as a template. Our method
      identifies conserved and unconserved subsequences within an RNA molecule. For
      conserved subsequences, the template structure is directly transferred into the
      generated structure and combined with de-novo predicted structure for the
      unconserved subsequences with low evolutionary conservation. The method also
      determines, when the generated structure is unreliable. The method is validated
      using experimentally identified structures. The accuracy of the method exceeds
      that of classical prediction algorithms and constrained prediction methods. This
      is demonstrated by comparison using large number of heterogeneous RNAs. The
      presented method is fast and robust, and useful for various applications
      requiring knowledge of secondary structures of individual RNA sequences.

PMID- 29067039
TI  - Management of community acquired pneumonia by Family Physicians.
AB  - BACKGROUND AND OBJECTIVE: Community Acquired Pneumonia (CAP)is a major burden on
      health systemwith significant mortality and morbidity. Family Physicians(FPs)can
      play important role. To determine management strategies and prescription of FPs
      regarding CAP. METHODS: A multicenter cross sectional survey was done in 10
      cities of Pakistan from November 2014 to January 2015. Self-administered
      questionnaire was filled by 110 Family Physicians. RESULTS: Of total 71% of FPs
      reported to work in high prevalence areas for respiratory ailments. Only 32% of
      FPs used PSI and 34% CURB 65 for assessment of severity. It was alarming to note
      that only 58% of FPs treats severe pneumonia with Intravenous antibiotics while
      rests were comfortable with oral route. The overall use of quinolones to treat
      CAP, irrespective of severity, in combination or as single agent was > 60%.
      Duration of antibiotics for severe pneumonia was sub optimal (<10 days). Only
      52.8% patients came back for follow-up so true outcome cannot be anticipated.
      CONCLUSION: Major deficiencies were treatment of severe pneumonia in community,
      inappropriate use of quinolones and poor knowledge of recent guidelines. This can
      lead to emergence of resistant bacteria and high mortality and morbidity. List of
      Abbreviations: FPs: Family Physicians, CAP: Community Acquired Pneumonia.

PMID- 29067040
TI  - Long Term Outcomes of Laparoscopic and Open Modified Lich-Gregoir Reimplantation
      in Adults: A multicentric comparative study.
AB  - BACKGROUND & OBJECTIVE: Obstructive ureteral pathologies in adult patients are
      most commonly due to ureteral strictures and secondary to surgical interventions.
      In this study, we aimed to compare open and laparoscopic modified Lich-Gregoir
      ureteral reimplantation with regards to outcomes in benign ureteral pathologies
      in adult patients. METHODS: Between December 2008 and December 2014, 32 open
      cases and 29 laparoscopic cases were performed as per the data retrieved from
      surgical databases. All laparoscopic procedures were performed in Bakirkoy Dr.
      Sadi Konuk Training and Research Hospital(BEAH) and all open ureteral
      reimplantation procedures in Kartal Dr Lutfi Kirdar Training and Research
      Hospital(KEAH) and Okmeydani Training and Research Hospital(OEAH). RESULTS: The
      mean operation time was significantly lower in the group of patients operated
      with open group (142.5 minutes versus 188.9 minutes; P< 0.0001). The mean
      duration of follow-up was longer in the laparoscopy group (31 versus 28 months;
      p< 0.0001). The mean amount of operation associated blood loss was significantly
      lower in patients operated laparoscopically (93.7 mL versus 214 mL; P< 0.0001).
      The mean VAS score obtained six hours after surgery was 6.6 +/- 0.8 in open
      group, and 5.8 +/- 0.7 in laparoscopic group (p=0.0004). The mean VAS scores
      measured at post-operative day 1 was 4.5 +/- 0.7 in open group and 3.7 +/- 0.9 in
      laparoscopy group. Time required to achieve the pre-operative capability of daily
      activities was significantly longer in open group (15 +/- 1.4 days vs 11 +/- 1.4
      days; p< 0.0001). CONCLUSION: Despite open techniques provide shorter operation
      time and laparoscopic techniques require long learning curve, we think that
      laparoscopic techniques are superior to open ones since that they provide a
      better post-operative comfort and are better tolerated in terms of complications.

PMID- 29067041
TI  - Paediatric Inflammatory Bowel Disease: Clinical Presentation and Disease
      Location.
AB  - OBJECTIVE: To determine different clinical presentationsand disease location
      demarcatedby upper and lower gastrointestinal endoscopyand relevant
      histopathologyin children diagnosed with inflammatory bowel disease (IBD).
      METHODS: This is 5 years (2010 to 2015) retrospective studyconducted at the Aga
      Khan University Hospitalenrolling65admitted children between 6 months to 15years
      from either gender, diagnosed with IBD on clinical presentation, endoscopy and
      biopsy. Different clinical presentations at the time of diagnosis were noted in
      different categories of the disease. All patients underwent upper and lower (up
      to the terminal ileum) endoscopy with multiple punch biopsies and histologic
      assessment of mucosal specimens. All endoscopies were done by paediatric
      gastroenterologists at endoscopy suite of the hospital and all specimens were
      reported by the pathology department. ESPGHAN revised criteria for the diagnosis
      of inflammatory bowel disease in children and an adolescent was used to
      standardize our diagnosis. Extent of disease on endoscopy and relevant
      histopathology of the biopsy samples were noted at the time of diagnosis. Data
      was summarized using mean, standard deviation, numbers and percentages for
      different variables. RESULTS: Total 56 children were enrolled according to
      inclusion criteria. There were 34children (61.53%) diagnosed with ulcerative
      colitis (UC), 10 patients (16.92%) had Crohn'sDisease (CD) and 11 (21.53%)
      patients were labeled as Indeterminate colitis (IC). Mean age at onset of
      symptoms was10.03+/-2.44 and mean age at diagnosis was11.10+/-2.36. Abdominal
      pain (80%) and chronic diarrhea (70%) were common symptoms in CD whereas bloody
      diarrhea (79.41%) and rectal bleeding(64.70%)were common presentation in UC.
      Patients diagnosed with indeterminate colitis(IC) had similar clinical features
      as in UC patients. Only 7% patients had some extra-intestinal features in the
      form of joint pain and/or uveitis. Aspartate aminotransferase level (95.18 +/
      12.89) was relatively high in patients withCD in comparison with other categories
      of IBD. Endoscopic findings and relevant histopathology of biopsy samples in UC
      showed 65% patient had pan-colitis and 13 % with disease restricted to rectum
      only whereas in CD 70% patient had disease in ileo-colon and only 10 % had
      involvement of ileum at the time diagnosis. CONCLUSION: Patients with UC
      dominated in our cohort. The most common clinical presentation in UC was bloody
      diarrhea and rectal bleeding and patients with CDhad abdominal pain and chronic
      diarrhea as predominant clinical features. Extraintestinal features were uncommon
      in our cohort. In endoscopic findings, pan-colitis was the mostfrequentfinding in
      UC and ileo-colonwas common location in CD. IC and UC shared common clinical
      features and disease location on endoscopy.

PMID- 29067042
TI  - A clinical study on arthroplasty for failed internal fixation of hip fractures
      and review of literature.
AB  - BACKGROUND & OBJECTIVE: Hip fracture is common osteoporotic fracture associated
      sometimes with failed internal fixation. Joint replacement is commonly used to
      salvage failed internal fixation of hip fractures (FIFHF). Our objective was to
      present the outcome of Arthroplasty after FIFHF in our patients. METHODS: A
      prospective analysis was made on consecutive patients who underwent prosthetic
      replacements for FIFHF in Orthopaedics Department of Xuanwu Hospital between June
      2012 and January 2015. Fifty six patients were included. There were 32 cases of
      failed internal fixation of femoral neck fracture (FIFFNF) and 24 cases of failed
      internal fixation of intertrochanteric fracture (FIFIF). The reoperations
      included 36 cases of total hip replacements, and 20 cases of bipolar femoral head
      replacements. Cemented prostheses were used in 19 patients (long-stems in 7
      patients), and uncemented prostheses in 37 patients (long-stems in 12 patients).
      The patients were followed up for a minimum of 12 months or until their death.
      RESULTS: Two patients died of pulmonary infection in the perioperative period,
      two died of myocardial infarction in two months after the operation, and the rest
      survived 12 month follow-up at the least. The mean Harris hip scores of the
      patients were 47 and 85 before and after the operation, respectively. The rate of
      Excellent and Good results is 82.7%. T tests showed that difference between pre
      and post-operation Harris hip scores is statistically significant (p <0.001).
      CONCLUSIONS: Arthroplasty may serve as a suitable salvage technique for FIFHF,
      and long-stem prosthesis replacement is proved to obtain reliable curative
      effect, especially in FIFIF.

PMID- 29067043
TI  - Surgical Outcome of Spontaneous Supra Tentorial Intracerebral Hemorrhage.
AB  - OBJECTIVE: To assess the risks and benefits of surgical treatment (Open
      Craniotomy) of Intra-cerebral hematoma (ICH). METHODS: Twenty seven patients of
      ICH who underwent surgical treatment at Neurosurgical department of Sheikh Zayed
      Hospital, Rahim Yar Khan, from 1st January 2015 to 31st December 2015 were
      included in this study. The primary outcome measured was death and improvement in
      GCS Status among survivor's at three months. RESULTS: Mean age of the patients
      was 58.4+/-10.7 and majority of patients (48.1%) were in the age range of 60-70
      years. There were22.2% patients with ICH volume of >50 ml. Six (6) patients had 8
      GCS with 50ml volume, who later died in ICU. Three of the patients who expired
      developed post-operative pneumothorax. These patients also acquired RTI resulting
      in deterioration of GCS. The rest of the expired patients showed deterioration in
      their GCS associated with oedma on brain CT scan. One patient died as a result of
      re-bleed. Twenty one (21) patients were discharged from hospital, two of these
      patients were lost in second follow up. Rest of the patients showed a gradual
      improvement in GCS touching 15/15 by 2nd follow up visit. CONCLUSION: Surgical
      prognosis of ICH depends on the patients GCS received and size of hemorrhage at
      the time of presentation. Urgent surgical evacuation in patients with rapid
      deterioration carries good outcome, hence should be considered.

PMID- 29067044
TI  - Acute kidney injury in Ureteric Stones:Single centre short term analysis.
AB  - OBJECTIVE: To analyze acute kidney injury (AKI) frequency, risk factors and
      outcome in ureteric stone patients. METHODS: This is an observational
      retrospective study performed in a single tertiary care centre in Abu Dhabi from
      October 2014 till August 2015. Convenient sampling was done on 152 consecutive
      patients who underwent decompression surgery (Ureterorenoscopy LASER Lithotripsy
      and DJ Stenting) for ureteric stones. Serum Creatinine was used to calculate
      creatinine clearance by cock croft Gault formula in all patients before and after
      procedure. Analysis was done on SPSS version 17. RESULTS: Out of 152 patients who
      under went decompression surgical procedure for ureteric stones AKI was seen in
      49(32.2%). Patients with AKI were found to be more higher age, increasedweight,
      bilateral stones, lower ureteric stones and with co morbidities in comparison to
      those who were without acute kidney injury. Patients developing AKI, 89.7%
      recovered either partially(20.4 %) or completely (69.3%). CONCLUSION: AKI is seen
      more in ureteric stone patients with older age, increased weight, bilateral
      stones, lower ureteric stones and with co morbidities. Recovery is good when
      obstruction is relieved.

PMID- 29067045
TI  - Rapid virological&End treatment response of patients treated with Sofosbuvir in
      Chronic Hepatitis C.
AB  - OBJECTIVE: To determineRapid & End treatment response of patients treated with
      Sofosbuvir in Chronic Hepatitis C at tertiary care hospital. METHODS: It was an
      observational study conducted at Memon Medical Institute from January 2016 to
      July 2017. The inclusion criteria for patients was 18 years of age or older,
      having chronic infection with HCV. Total=201 received sofosbuvir with or without
      interferon in our OPDs. Patients were categorized into Treatment naive, treatment
      experienced and decompensated chronic liver disease. Pregnant patients and those
      not willing to participate were excluded. Initially genotyping and Quantitative
      HCV RNA test was done. RESULTS: A total of 201 subjects were included in the
      study with mean age of the patients was 46.22+/- 14.41 years. Of 201 patients, n=
      131 (65.2%) chronic hepatitis C, compensated cirrhosis n= 47(23.4%), and with
      decompensated cirrhosis n=23(11.4%). Most commonly genotype 3 n= 180 (89.6%) was
      present followed by genotype 1 n=9(4.5%), genotype 2 n=1(0.5%), genotype 4
      n=1(0.5%). Of patients with genotype 3, 123 received dual therapy and 57 were
      given triple therapy. After one month of therapy HCV RNA by PCR, 200(99.5%)
      achieved RVR, 199(99%) achieved ETR and SVR achieved in 178(88.5%) while
      remaining 1 patient did not achieved RVR, 2 ETR and 12 patients did not achieved
      SVR and remaining 11 SVR lost follow up. CONCLUSION: Sofosbuvir has shown to be
      very effective andsuccessfulwith achievement of virological response with little
      or no resistance in all genotypes mainly genotype 3 treated in our study
      population. The promising results of our study will aid in better outcomes and
      therefore help in eradication of the virus.

PMID- 29067046
TI  - Subclinical Hypothyroidism: Frequency, clinical presentations and treatment
      indications.
AB  - OBJECTIVE: To determine the frequency, modes of clinical presentation and
      indications for replacement therapy in a cohort of patients with subclinical
      hypothyroidism (SCH). METHODS: This study was conducted at the Endocrine and
      Diabetes Unit of Jinnah Postgraduate Medical Centre from September 2007 - October
      2015. This was a retrospective chart analysis of prospectively collected data in
      whichthe medical records of 4448 patients who had presented to the Endocrine
      Clinic from 2007 to 2015 were reviewed. A total of 2760 (62.05%) patients were
      diagnosed withthyroid disorders, whereas 260 (9.42%) patients had SCH. The SCH
      patients were between the age of 12 to 70 years; TSH was> 4mIU/l with normal
      levels of FT3 and FT4. Patients were enrolled using a predesigned structured
      proforma. Those having chronic systemic diseases were excluded from this study.
      SPSS 13 was used to evaluate the data. RESULTS: Femalepatients comprised93.8%
      (244 patients) of those with SCH, whereas only 6.2% (16 patients) were male.
      Common presenting symptoms were, lethargy in 146 patients (56.2%); increase in
      weight in 102 patients (39.2%) and menstrual irregularities in 90 patients
      (34.6%). TSH level of < 10mIU/l (4 - 10) was seen in 177 patients (68.1%) and 83
      patients (31.9%) had TSH >= 10mU/l. Thyroxine was given to 183 (70.4%) of these
      patients. Common treatment indications were TSH of >= 10, which was seen in 83
      patients (31.9%), subfertility in 32 patients (12.3%), troublesome symptoms
      suggestive of hypothyroidism in 31 patients (11.9%) and high titers of antibodies
      in 23 patients (8.8%). CONCLUSION: SCH is frequently seen in our population, with
      most patients complaining of lethargy. The most common treatment indications were
      a TSH >= 10mIU/l, whereas troublesome symptoms of hypothyroidism and subfertility
      were the common treatment indications in patients who had a TSH of < 10mIU/l.

PMID- 29067047
TI  - The use of flexible laryngeal mask airway for Adenoidectomies: An experience of
      814Paediatric patients.
AB  - OBJECTIVE: To assess flexible laryngeal mask airway (F-LMA) use during pediatric
      adenoidectomies in terms of patient safety, comfort, complication rates and
      surgeon satisfaction levels. METHODS: Patients who had undergone an elective
      adenoidectomy after receiving general anesthesia using F-LMA from June 2012 to
      November 2015 were included. Patients' demographics and the incidence of
      perioperative complications were investigated. The surgeon's satisfaction level
      was also evaluated by questionnaire. RESULTS: Eight hundred fourteen patient were
      included in the study. Conversion from F-LMA to an endotracheal tube was carried
      out in two patients (0.2%). Airway complications were identified in two patients.
      The mean duration of stay in the postoperative anesthesia care unit was 17
      minutes. All patients were discharged the same day. According to the
      otolaryngologists F-LMA applications provide a significant reduction in the
      processing time (100%), postoperative patient comfort is better than when using
      endotracheal intubation (83.3%) and the consensus was that there should be a
      complete continuation of the use of the F-LMA (100%) in subsequent
      adenoidectomies. CONCLUSION: Our data show that the use of F-LMA for pediatric
      adenoidectomies has well tolerability profile and resulted in a lower incidence
      of complications. We think that the use of F-LMA for pediatric adenoidectomy is
      safer, simpler and speeder method.

PMID- 29067048
TI  - Illness Perceptions in Patients of Schizophrenia: A Preliminary Investigation
      from Lahore, Pakistan.
AB  - BACKGROUND AND OBJECTIVE: Patient's perception of their illness influences their
      healthcare decisions. The objectives of this study were to explore patient's own
      beliefs about their illness (Schizophrenia) and perceived social support, and its
      impact on their attitudes toward pharmacological treatment in Lahore, Pakistan.
      METHODS: This study was conducted at Mayo Hospital Lahore from March to September
      2016. Hundred individuals suffering from Schizophrenia completed four
      questionnaires; a socio-demographic questionnaire, the Illness Perception
      Questionnaire for Schizophrenia(IPQ-S), Drug attitude Inventory-10 (DAI) and
      Multidimensional Scale of Perceived Social Support (PSS). RESULTS: Stress, family
      problems, lack of friends & financial worries were endorsed strongly by patients
      as cause of their mental illness. Ambiguity regarding their mental illness
      duration and personal control was observed. Patients' perceived significant
      negative consequences, negative emotional response, as well as had poor
      understanding of their mental illness and treatment effectiveness. Statistically
      significant gender differences in treatment control and illness coherence
      subscales of IPQS were observed. Drug attitude inventory was positively
      correlated with Treatment control subscale (p < .01) and negatively correlated
      with Illness coherence subscale of IPQS (p < .05). The negative consequences
      subscale and perceived social support was negatively correlated (p < .01).
      CONCLUSION: Patient's perception about their own illness is predictor of their
      drug taking attitude and perceived social support. Study results should help to
      develop new interventions to correct inaccurate beliefs in patients with
      schizophrenia to improve illness outcome.

PMID- 29067049
TI  - An epidemiological study of prevalence and comorbidity of obsessive compulsive
      disorder symptoms (SOCD) and stress in Pakistani Adults.
AB  - OBJECTIVE: To investigate the prevalence and comorbidity of subclinical obsessive
      compulsive disorder (SOCD) symptoms and stress across gender, marital and
      employment statuses. METHODS: A cross-sectional research was conducted from
      December, 2016 to March 2017 at two universities of cosmopolitan city Lahore. Two
      self-report scales measuring SOCD symptoms and stress were used to collect data
      from 377 adults selected through simple random sampling technique,
      proportionately distributed across gender, marital and employment status.
      RESULTS: From the total sample, 52% reported low level of stress and 48% faced
      high level of stress. Significant differences in prevalence were observed across
      marital and employment statuses whereas for men and women, it was observed same
      (24%). Comorbidity of high level of SOCD symptoms and high level of stress was
      seen 34%. CONCLUSION: Significant prevalence and comorbidity exists between SOCD
      symptoms and stress and more studies addressing diverse population are needed.

PMID- 29067050
TI  - Delayed conventional DMARDs therapy is effective in Rheumatoid Arthritis.
AB  - OBJECTIVE: To determine the disease severity in patients with Rheumatoid
      Arthritis (RA), at baseline and the impact of treatment on disease activity (DA)
      after six months of disease modifying anti-rheumatic drugs (DMARDs) therapy.
      METHODS: This prospective study was conducted at the 'Rheumatology Clinic' of
      Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 2014 to May 2015. A
      total of 111 patients, with the diagnosis of RA were included in the study. DA
      was calculated using 'Clinical Disease Activity Index' (CDAI) score at base line
      and after 6 months of DMARDs therapy. RESULTS: Out of 111 patients, 17 (15.3%)
      were male and 94 (84.7%) were female. The mean age was 37.16+/-11.3 years and the
      mean duration of joint pain was 3.8+/-3.6 years (median 2.5 years). The mean Hb
      was 10.8+/-1.8 g/dl and the mean ESR at baseline was 59.63+/-30.9 mm/Hr. The mean
      initial CDAI score was 18.14+/-11.69; reflecting moderate to severe disease. Of
      all of these patients, 32 (28.8%) patients received monotherapy, 78 (70.3%)
      received dual therapy and 1(0.9%) was given triple DMARDs therapy. The mean ESR
      was 39.5+/-27.31 mm/Hr, and mean CDAI was 7.36+/-7.8 with a median of 6.0 after 6
      months of DMARDs treatment. CONCLUSION: The CDAI score and the ESR reflected that
      majority of our patients were in remission or at low disease activity, after six
      months of DMARDs therapy. It is possible to control DA in RA, in a low resource
      health care facility with conventional DMARDs therapy. Continuity of treatment
      was ensured through motivation, regular supply of drugs and regular follow-up.

PMID- 29067051
TI  - Correlation between the Expression of Topo IIalpha and Ki67 in breast cancer and
      its clinical Pathological characteristics.
AB  - OBJECTIVE: To investigate the expression of Topo IIalpha and Ki67 and its
      clinical significance. METHODS: The clinical pathological data of one hundred and
      sixteen invasive breast cancer patients who were admitted into our hospital from
      July 2013 to December 2015 and underwent radical mastectomy were retrospectively
      analyzed. The expression of topoisomerase (Topo) IIalpha and Ki67 was detected
      using immunohistochemical method, and the correlation between the two kinds of
      proteins and the general clinical pathological characteristics of the patients
      was analyzed. RESULTS: The positive expression rates of Topo IIalpha and Ki67 in
      breast cancer were 58.6% and 75% respectively. The expression of Topo IIalpha was
      in no apparent correlation with the age, tumor size, estrogen receptor (ER),
      progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2)
      (P>0.05), but in a correlation with the number of metastatic lymph glands
      (P<0.05). The expression of Ki67 was in no apparent correlation with the age,
      tumor size, EP and HER-2, but in a correlation with the number of metastatic
      lymph glands and PR (P<0.05). The multi-factor logistic regression analysis
      results suggested that the number of metastatic lymph glands was the independent
      predictive factor of Topo IIalpha positive expression and the number of
      metastatic lymph glands and PR protein expression state are the independent
      predictive factors of Ki67 positive expression. CONCLUSION: Topo IIalpha and Ki67
      can be regarded as the indicators for reflecting the proliferation activity of
      tumor cells, and the detection of Topo IIalpha and Ki67 expression is of great
      significance to the prognosis evaluation of breast cancer patients and clinical
      treatment.

PMID- 29067052
TI  - Utilization Focused Evaluation at Bahria University Medical & Dental College.
AB  - OBJECTIVE: To evaluate integrated learning program of neurosciences for
      continuation of integrated learning in the forthcoming teaching and learning
      modules of undergraduate medical curriculum at Bahria University Medical & Dental
      College (BUMDC). METHODS: A mixed method design was conducted from August 2016to
      February2017 after ethical approval from BUMDC. The quantitative aspect was
      evaluated retrospectively by desk records ofmarks obtained in integrated module
      and nonintegrated module. Focused group discussionwere conducted with primary
      intended users (chair of integration committee, faculty and students of first and
      second year MBBS)to share their expectations and concerns and get responses on
      key evaluation questions for implementationand outcome evaluation of integrated
      learning program. RESULTS: The desk record revealed a positive perception of
      students and faculty at the time of implementation with improvement in results
      after integration in subjects of basic sciences. The discussions highlighted
      reasons which resulted in failure of its continuation and affirmedreadiness for
      re-induction and continuation of integration with clinicalsciences. CONCLUSION:
      Evaluators considered approval and re-application of integrated curriculum at
      BUMDC after utilization focused evaluation.

PMID- 29067054
TI  - The potential effect of technology and distractions on undergraduate students'
      concentration.
AB  - BACKGROUND AND OBJECTIVES: In the present era, it is difficult to keep the
      concentration of college students at its maximum potential during the class time,
      as there are many distractions that negatively impact students' concentration and
      prevent optimal learning. Technologies such as laptops and cell phones have
      invaded the classroom, raising considerable concerns about their effects on
      college students' attention in the classroom. Despite these concerns, no research
      has been done in Saudi Arabia on the effects of technology and other types of
      classroom distractions on students' concentration. In the current study, we have
      attempted to identify students' perceptions of major distractions in the
      classroom based on seventeen internally (self-produced) and twenty-four
      externally produced classroom situations. METHODS: The students participating in
      this study rated the degree to which each distraction interferes with their
      concentration on the class materials and their ability to learn. Data were
      collected through surveys of 265 students (66 and 199 students from medical and
      basic classes, respectively), including 97 females and 168 males 17-23 years of
      age from the academic years 2010 to 2014. A validated self-administered
      questionnaire was handed to the students in the classroom. The students were
      asked to report and rate the classroom distraction produced by 24 external
      internal distracters (Table-II), on a 5-point scale. RESULTS: The results
      revealed that ringing cell phones in the class were the most commonly reported
      electronic external distractor for 68% of students, and 21% of them reported
      being extremely distracted by this noise. Having an instructor who is difficult
      to understand was the most commonly reported external behavioral distractor for
      75% of students, and 48% of them rated this as extremely distracting. Students
      talking in class were the most self-produced distractor for 72% of students;
      negatively impacting their concentration and ability to learn, and 42% of them
      rated it as an extreme distractor. Wearing clothing with unusual words, drinking
      and eating in the classroom were minimally distracting colleagues. Overall,
      distractions (internal and external) were more significant for fifth-year
      students than the other years at a p-value < 0.001. CONCLUSION: Students believed
      that laptop and cell phone use in the classroom can effect their concentration
      and ability to learn. The students also felt that inappropriate behavior is a
      major distraction for students as well, and thus necessitates monitoring and
      improvement.

PMID- 29067053
TI  - Pelvic floor muscle strength of women consulting at the gynecology outpatient
      clinics and its correlation with sexual dysfunction: A cross-sectional study.
AB  - OBJECTIVE: To investigate the pelvic floor muscle strength of the women
      andevaluateits possible correlation with sexual dysfunction. METHODS: In this
      cross-sectional type study, stratified clusters were used for the sampling
      method. Index of Female Sexual Function (IFSF) worksheetwere used for questions
      on sexual function. The pelvic floor muscle strength of subjects was assessed
      byperineometer. The chi-squared test, logistic regression and Pearson's
      correlation analysis were used for the statistical analysis. RESULTS: Four
      hundred thirty primiparous women, mean age 38.5 participated in this study. The
      average pelvic floor muscle strength value was found 31.4+/-9.6 cm H2O and the
      average Index of Female Sexual Function (IFSF) score was found 26.5+/-6.9. Parity
      (odds ratio OR=5.546) and age 40 or higher (OR=3.484) were found correlated with
      pelvic floor muscle weakness (p<0.05). The factors directly correlated with
      sexual dysfunction were found being overweight (OR=2.105) and age 40 or higher
      (OR=2.451) (p<0.05). Pearson's correlation analysis showed that there was a
      statistically significantlinear correlation between the muscular strength of the
      pelvic floor and sexual function (p=0.001). CONCLUSION: The results suggested
      subjects with decreased pelvic floor muscle strength value had higher frequency
      of sexual dysfunction.

PMID- 29067055
TI  - Evaluation of Cognitive levels and Item writing flaws in Medical Pharmacology
      Internal Assessment Examinations.
AB  - OBJECTIVES: This study aimed to evaluate the cognitive levels of Multiple Choice
      Questions (MCQs) & Short Answer Questions (SAQs) and types of Item Writing Flaws
      (IWFs) in MCQs in Medical Pharmacology internal assessment exams. METHODS: This
      descriptive, study was conducted over a period of six months, from December 2015
      to May 2016 and evaluated six internal assessment examinations comprising SAQs
      and MCQs. A total of 150 MCQs and 43 SAQs were analyzed. These questions were
      administered to third-year medical students in the year of 2015. All SAQs were
      reviewed for their cognitive levels and MCQs were reviewed for cognitive levels
      as well as for IWFs. Items were classified as flawed if they contained one or
      more than one flaw. The cognitive level of the questions was determined by the
      modified Bloom's taxonomy. RESULTS: The proportion of flawed items out of 150
      items in six exams ranged from 16% to 52%. While the percentage of total flawed
      items was 28%. Most common types of flaws were implausible distractors 19.69%
      (26), extra detail in correct option 18.18% (24), vague terms 9.85% (13),
      unfocused stem 9.09% (12) and absolute terms 9.09% (12). The two-third of MCQs
      97(64.67%) were assessing the recall of information, while 29 (19.33%) and 24
      (16%) were assessing the interpretation of data and problem-solving skills
      respectively. The majority of the SAQs (90.7%) were assessing recall of the
      information and only 9.3% were assessing interpretation of data while none of the
      questions was assessing the problem-solving skills. CONCLUSIONS: The cognitive
      level of assessment tools (SAQs & MCQs) is low, and IWFS are common in the MCQs.
      Therefore, faculty should be urged and groomed to design problem-solving
      questions which are devoid of any flaws.

PMID- 29067056
TI  - Mean Platelet Volume in Graves' disease: A Sign of Hypermetabolism Rather than
      Autoimmunity?
AB  - OBJECTIVE: To evaluate the impact of mean platelet volume (MPV) on predicting
      disease course among patients with Graves' disease (GD). METHODS: This
      retrospective study was performed between 2013-2016 at the Outpatient
      Endocrinology Clinic of Baskent University Faculty of Medicine, Adana hospital on
      65 patients with GD. Among participants, 30 cases experienced thyrotoxicosis
      again during the first six months after discontinuing anti-thyroid drug (ATD)
      sessions that had been carried out for at least 12 months prior to stopping
      (Relapse group). We also observed 35 patients who exhibited normal thyroid
      functions within six months following ATD withdrawal (Remission group). MPV
      levels and thyroid function tests were recorded and total duration of ATD therapy
      was calculated for all participants. RESULTS: The mean MPV level that was
      measured at the time of drug withdrawal did not differ between groups, being
      8.0+/-1.2 fL in the Relapse group vs. 8.0+/-1.0 fL in the Remission group
      (p=0.81). However, we found that the relapse MPV was higher than the withdrawal
      MPV in the Relapse group (9.2+/-1.3 fL) than it was in the Remission group (8.0+/
      1.2 fL, p=0.00). CONCLUSIONS: Higher relapse MPV in Relapse group but similar MPV
      levels in both groups at ATD withdrawal may be attributed to hypermetabolism or
      hyperthyroidism rather than autoimmunity of GD. Abbreviations:BMI: Body mass
      index GD: Graves' disease MPV: Mean platelet volume TSH: Thyroid-stimulating
      hormone TRAbs: Thyrotropin receptor antibodies ATD: Anti-thyroid drug fT4: Free
      thyroxine fT3: Free triiodothyronine CBC: Complete blood count PTC: Papillary
      thyroid carcinoma.

PMID- 29067057
TI  - A comparison of anxiety and depression between pre-dialysis chronic kidney
      disease patients and hemodialysis patients using hospital anxiety and depression
      scale.
AB  - OBJECTIVE: Tocompare frequency of anxiety and depression between pre-dialysis
      chronic kidney disease (CKD) and hemodialysis patients (ESRD) in Pakistan.
      METHODS: This study was conducted in an out-patient department and hemodialysis
      unit of Sharif Medical City Hospital. Inclusion criteria included age above 18
      years and a diagnosis of CKD including both pre-dialysis CKD and ESRD patients.
      Patients were screened for anxiety and depression using hospital anxiety and
      depression scale (HADS). RESULTS: A total of 156 patients were included in the
      study. Out of these patients, 81 (51.9%) had ESRD and 75 (48.1%) had pre-dialysis
      CKD. Mean age of all patient was 47.3+/-18.3 years, 96 (61.5%) were males and 60
      (38.5%) were females. Median duration of renal disease was 16 months (IQR 8-36
      months). Anxiety and depression were present in 111 (71.2%) and 113 (72.4%) of
      all patients respectively. Moderate to severe anxiety and depression were present
      in 54 (34.6%) and 60 (38.5%) patients respectively. In multiple logistic
      regression model, after adjusting for other variables, ESRD vs. pre-dialysis CKD
      was significantly associated with moderate to severe depression (AOR 2.26 (1.1
      5.1). CONCLUSION: Both anxiety and depression are common in pre-dialysis CKD and
      ESRD patients. Patients with ESRD have higher frequency of depression compared to
      pre-dialysis CKD patients.

PMID- 29067058
TI  - Effect of Vitamin D supplementation on reduction in levels of HbA1 in patients
      recently diagnosed with type 2 Diabetes Mellitus having asymptomatic Vitamin D
      deficiency.
AB  - OBJECTIVE: To study the effect of Vitamin D supplementation on reduction in level
      of HbA1 in patients recently diagnosed with diabetes mellitus Type II having
      asymptomatic Vitamin D deficiency. METHODS: This randomized control trial was
      conducted at East Medical Ward Mayo Hospital Lahore for 6 months from January 01
      2016 to June 30, 2016. 114 Patients were included through non probability
      purposive sampling technique. Informed consent and demographic information was
      collected. Patients were divided in two groups by randomization through tossing a
      coin. Group-A patients received Metformin tablet alone at 500 mg after dinner and
      Group-B patients were treated with same dosage of Metformin along with oral
      vitamin D at 200,000 IU monthly for three months. Blood sample was obtained at
      baseline, 3 months and 6 months of initiation of therapy. All samples were sent
      to the laboratory for complete blood count, blood sugar fasting, serum calcium,
      serum phosphorous, serum alkaline phosphatase, HbA1c and serum 25 Hyroxy Vitamin
      D (S-25(OH) D) levels and iPTH. Data entry and analysis was done by using SPSS
      20. RESULTS: The mean age of patients in metformin group was 42.37+/-4.59 years
      while mean age of patients in combination group was 43.33+/-4.86years. Males were
      45.6% and females were 54.4% in metformin group while in combination group, 36.8%
      were males' and 63.2% were females'. At baseline, in metformin group, mean
      Vitamin D level was 17.09+/-1.73mg/dl and in combination group, mean Vitamin D
      level was 16.49+/-1.56mg/dl. The difference was insignificant (p>0.05). On 2nd
      visit, combination group mean Vitamin D was 29.04+/-3.96mg/dl. At baseline, 1st
      and 2nd visit, in metformin group, mean HbA1c was 7.59+/-0.47%, 7.46+/-0.25% and
      7.30+/-0.29%. At baseline, 1st and 2nd visit, in combination group, mean HbA1c
      was 7.71+/-0.19%, 7.57+/-0.21% and 7.43+/-0.26%. The difference was insignificant
      (p>0.05) at baseline while significant on later follow-ups (P<0.05). CONCLUSION:
      Vitamin D supplementation improved the glycemic control but substantial reduction
      in HbA1c was statistically insignificant in both groups.

PMID- 29067059
TI  - Phenotypic characterization of extended-spectrum-beta-lactamase producing E. coli
      from healthy individuals, patients, sewage sludge, cattle, chickens and raw meat.
AB  - OBJECTIVE: The present study aimed to determine the frequency and antimicrobial
      profile of ESBL-producing isolates of E. coli in different environments. METHODS:
      This cross-sectional study was conducted at The Children's Hospital and The
      Institute of Child Health, Lahore from July to December 2015. The faecal
      specimens from healthy individuals, patients, sewage sludge, cattle, chickens and
      raw meat (n = 122) were processed for microbiological analysis using MacConkey
      agar supplemented with cefotaxime. The identification of organisms was confirmed
      by API 10S and antimicrobial resistance profile was recorded by Kirby-Bauer disc
      diffusion method. RESULTS: On the basis of screening, 77 (63.0%) specimens were
      found to be positive for ESBL production. The confirmation of 74 (60.0%) ESBL
      producing E. coli was done using double disc synergy test (DDST). The frequency
      of ESBL producing E. coli was found to be 17 (57.0%) in healthy individuals, 15
      (53.0%) in patients, 10 (66.0%) in cattle faeces, 5 (71.0%) in sewage sludge, 14
      (70.0%) in raw meat and 13 (59.0%) in chicken faeces. All of these isolates were
      resistant to cephalosporins and some of these were resistant to fluoroquinolones
      and meropenem. None of the isolates showed resistance to cefoperazone-sulbactam,
      imipenem, piperacillin-tazobactam and amikacin. CONCLUSION: The prevalence of
      ESBL-producing E. coli was recorded in all the environments, suggesting a global
      expansion of these enzymes.

PMID- 29067060
TI  - Clinical comparative study on Nitrous Oxide inhalation versus intravenous
      propofol and Midazolam sedation in Transnasal Gastroscopy.
AB  - OBJECTIVE: To investigate the Clinical practice value of nitrous oxide inhalation
      and intravenous propofol and midazolam sedation in transnasal gastroscopy.
      METHOD: From December 2012 to April 2014, two hundred patients receiving painless
      transnasal gastroscopy on a voluntary basis were selected in Endoscopy center,
      The First People's Hospital of GuiYang. Patients were divided into two groups:
      Group-1 consisted of one hundred patients sedated by nitrous oxide inhalation and
      Group-2 consisted of one hundred patients sedated by intravenous propofol and
      midazolam. Patients were then examined by transnasal gastroscopy. Patient blood
      pressure, heart rate, pulse rate and oxygen saturation before, during and after
      gastroscopy were recorded for both groups. The duration of the gastroscopy and
      the time of awakening were also recorded. After examination, the patients were
      asked to assess the level of discomfort experiences during the gastroscopy
      procedure. RESULTS: All patients successfully underwent the transnasal
      gastroscopy. There were 57 males and 43 females in the nitrous oxide inhalation
      group with an average age of 43.11+/-8.27 years. The average duration of
      examination and time of awaking in the nitrous oxide inhalation group was of
      152.7+/-9.80 secs and 50+/-7.89 secs respectively. For the intravenous propofol
      and midazolam sedation group, there were 53 males and 47 females with an average
      age of 41.26+/-7.98 years. The average duration of examination and time of
      awaking in the intravenous propofol and midazolam sedation group was of 149.07+/
      10.25 seconds and 390+/-20.89# seconds respectively. The two groups showed no
      significant difference in the duration of examination. There was no difference in
      the age or sex. The former had a less significant impact on heart rate, oxygen
      saturation and blood pressure, while the intravenous propofol and midazolam
      sedation decreased blood pressure dramatically and this effect persisted after
      examination. CONCLUSION: Nitrous oxide inhalation has higher safety and tolerance
      with a brighter application prospect for transnasal gastroscopy.

PMID- 29067061
TI  - The assessment of mortality and quality of life after intertrochanteric fracture
      of femur in patients older than 60 at Emam Khomeini Hospital of Ahvaz.
AB  - OBJECTIVE: To investigate the mortality and disability rates after surgical
      treatment of intertrochanteric fractures in patients older than 60 years old.
      METHOD: In this retrospective study, 385 patients aged 60 or older who were
      admitted because of intertrochanteric fracture to treatment and teaching center
      of Emam Khomeini hospital of Ahvaz, Iran between Mar. 2010 to Feb. 2015 and
      underwent surgery were included. All the patients were treated by open reduction
      and internal fixation by dynamic hip screw. Two hundred and six patients were men
      (53.5%) and 179 were women (46.4%). Age of patients was between 60 to 89 years
      old with the average of 75.2 years old. Minimum time required after surgery to
      enter this study was one year. Results were gathered based on examination of
      patient or calling patients and their families by phone number. RESULT: Rate of
      mortality was 36.9%, including 54.9% for men and 41.9% for women. In eleven
      patients (2.85%), initial reduction was lost because of failure of fixation
      device. For these patients reoperation was performed, and 7 of them (63.63%)
      expired within the mean of 10.1 months after reoperation. Time delay for surgery
      after occurrence of the fracture was in range of 2 to 15 days with an average of
      4.8 days.24 patients (6.23%) went under surgery later than one week after
      fracture had been happened which seven of them (29.16%) expired. Highest
      mortality rate was in the age group of 80-89 years old with 50 patients (63.01%)
      and lowest one was in the group of 60-69 years old with three patients (4.67%).
      Disability rate and quality of life of the patients was measured by Modified
      Harris Hip Score and divided in 3 group of good (with a score of 71 to 90), fair
      (with a score of 51 to 70) and weak (with a score of 0 to 50). Patients who had
      good score consisted of 35.54% of patients with the average age of 64.63 years
      old and majority of male patients, fair group consisted of 30.5% of patients with
      average age of 73.45 years old and equal percentage of male and female patients
      and for Weak group it was 34.2% and 73.45 years old and by majority of male
      patients. CONCLUSION: Mortality rate of intertrochanteric fracture of femur is
      high even after treated with surgery and it's highly related to age of patient.
      Furthermore, quality of life after surgery is still low and follow up of the
      patients should be improved.

PMID- 29067062
TI  - Efficacy of early oral refeeding in patients of mild acute pancreatitis.
AB  - OBJECTIVE: To compare Early Oral Refeeding (EORF) with Routine Oral Refeeding
      (RORF) on outcome of patients of mild Acute Pancreatitis (AP) in terms of Mean
      Length of Hospital Stay (LOHS). METHODS: This randomized controlled trialwas
      conducted atSurgical Department CMH Rawalpindi, from 1st Feb 2015 to 01st Aug
      2016. A total of 60 patients with pain epigastrium were enrolled in the study.
      Severity of pancreatitis was assessed using Glasgow Scale. Patients were randomly
      divided in two groups. Group-A was started feeding within 12 hours (EORF group)
      and Group-B after 12 hours (RORF group). Demographic details and data were
      recorded on a structured proforma. After discharge, LOHS was measured for both
      groups and outcome was compared. RESULTS: The groups were comparable with respect
      to age, sex, etiology, Glasgow Scale, time from onset of pain and Serum Amylase
      levels at admission. Treatment was standardized according to international
      guidelines for both groups. The mean LOHS was 7.8 +/- 2.14 days in the Group-A
      and 10.03 +/- 1.75 days in Group-B. The difference in the mean LOHS between the
      two groups was statistically significant (p<0.05). CONCLUSION: In patients of
      mild acute pancreatitis, early oral feeding is feasible and safe and has better
      outcome then those with routine oral refeeding.

PMID- 29067063
TI  - Identifying a parsimonious model for predicting academic achievement in
      undergraduate medical education: A confirmatory factor analysis.
AB  - OBJECTIVES: This study was conducted to adduce evidence of validity for
      admissions tests and processes and for identifying a parsimonious model that
      predicts students' academic achievement in Medical College. METHODS: Psychometric
      study done on admission data and assessment scores for five years of medical
      studies at Aga Khan University Medical College, Pakistan using confirmatory
      factor analysis (CFA) and structured equation modeling (SEM). Sample included 276
      medical students admitted in 2003, 2004 and 2005. RESULTS: The SEM supported the
      existence of covariance between verbal reasoning, science and clinical knowledge
      for predicting achievement in medical school employing Maximum Likelihood (ML)
      estimations (n=112). Fit indices: chi2 (21) = 59.70, p =<.0001; CFI=.873; RMSEA =
      0.129; SRMR = 0.093. CONCLUSIONS: This study shows that in addition to biology
      and chemistry which have been traditionally used as major criteria for admission
      to medical colleges in Pakistan; mathematics has proven to be a better predictor
      for higher achievements in medical college.

PMID- 29067064
TI  - Another face of violence against women: Infertility.
AB  - BACKGROUND & OBJECTIVE: Violence against women is a widespread problem and has
      serious implications on women's health. Infertility, in many ways, is a very
      stressful condition that affect social and marital life of a couple; moreover,
      compared to fertile women, infertile women are twice as vulnerable against
      violence. Our objective was to determine the prevalence of violence and define
      the effect of infertility on violence on women receiving infertility treatment.
      METHODS: Descriptive and cross-sectional study was carried out 301 infertile
      women between November 2015 and August 2016 in a state hospital, Izmir. Data were
      collected as "Sociodemographic Characteristics Form" and "Infertile Women's
      Exposure to Violence Determination Scale". RESULTS: The mean age of women was
      31.77+/-5.46 years; the average duration of marriage was 6.93+/-4.53 years. About
      32.5% of women stated that they have suffered from violence throughout their
      lives and 4.7% of women were still suffering from violence, while 5.0% of women
      were subjected to violence after infertility was diagnosed. CONCLUSION: It is an
      encouraging finding that infertile women have a low exposure to violence.
      However, despite a low violence rate, there is an increase in violence toward
      women who have been diagnosed with infertility.

PMID- 29067065
TI  - Mini titanium plates; hearkening the end of non-rigid cranial bone flap fixation.
AB  - BACKGROUND AND OBJECTIVE: Craniotomy bone flaps should be replaced for both
      cosmetic and protective purposes. Different methods are available commercially.
      The aim of this study was to assess outcome of bone flap fixation using mini
      titanium plates and screws. METHODS: Between March, 2011 and March, 2014, 71
      patients underwent cranial bone flap fixation with mini titanium plates and
      screws after craniotomy and excision of supratentorial lesions at Combined
      Military Hospital, Peshawar. There were 42 males and 30 females with a mean age
      of 40.07. All patients had supratentorial lesions. Intracranial lesion size
      ranged from 3 cm by 2 cm to 7 cm by 5 cm. The changes of local incision and
      general condition were observed. RESULTS: Subcutaneous effusion occurred in two
      patients. One patient developed a mild postoperative wound infection. CT scan
      showed good repositioning of the flap and edge to edge apposition at two weeks
      after operation. All the patients were followed up for 12 months post
      operatively. Skull had good appearance without any discharge and, local deformity
      or effusion. Repeat CT/MRI showed no subsidence or displacement of cranial flap
      or artifacts. CONCLUSION: Mini titanium plate and screw fixation of cranial flaps
      is a simple, cost effective and safe option for repositioning and immediate
      stability as compared to traditional sutures.

PMID- 29067066
TI  - hsCRP and ET-1 expressions in patients with no-reflow phenomenon after
      Percutaneous Coronary Intervention.
AB  - OBJECTIVE: To explore hsCRP and ET-1 expressions in patients with no-reflow
      phenomenon after percutaneous coronary intervention (PCI). METHODS: A total of
      136 patients with single coronary artery disease receiving PCI were divided into
      a reflow group and a no-reflow group to compare the level use of ET-1 alone with
      combined level of ET-1 and hs-CRP in PCI regarding sensitivity, specificity,
      positive and negative predictive values and accuracy for postoperative no-reflow.
      The study was conducted between 2014-2016 at our hospital. RESULTS: Postoperative
      levels of ET-1 and hs-CRP in no-reflow group were significantly higher than those
      of reflow group (P<0.05). ET-1 level of reflow group peaked three hours after PCI
      and then declined. Serum level of hs-CRP decreased most obviously within three
      hours after PCI in reflow group and three hours - three days after PCI in no
      reflow group. Left ventricular end-diastolic diameters of both groups after PCI
      were apparently lower than those before PCI, without significant inter-group
      difference (P>0.05). Left ventricular end-systolic diameters and left ventricular
      ejection fractions of both groups evidently increased after PCI, without
      significant inter-group differences either (P>0.05). Corrected TIMI frame count
      (CTFC) and wall motion score index of reflow group after PCI were significantly
      lower than those of no-reflow group (P<0.05). ET-1 level was positively
      correlated with CTFC (P<0.05). Multivariate linear regression showed hs-CRP was
      negatively correlated with the serum level (P<0.05) (r=-0.34). CONCLUSION: hsCRP
      and ET-1 levels significantly increased in patients with no-reflow phenomenon.

PMID- 29067067
TI  - An analysis of 3105 Medico Legal Cases at Tertiary Care Hospital, Rawalpindi.
AB  - BACKGROUND AND OBJECTIVES: Medico legal cases are essential component of medical
      practice and comprise most important constituent of emergencies. The reporting of
      such cases is imperative to recognize theirsocioeconomic burden on any country.
      The present study was conducted to scrutinize different categories of medico
      legal cases and characteristics of the victims at casualty department oftertiary
      care hospital Rawalpindi. The objective of the study was to find out the
      frequency ofvarious categories of medico legal cases and major characteristics
      ofvictims at tertiary care hospital, Rawalpindi. METHODS: This was a cross
      sectional study on 3105 registered cases in medico legal record of the casualty
      department of Benazir Bhutto hospital, Rawalpindi from January 2015 to December
      2015. The hospital is located on the main road in densely populated central area
      of the city. The data wascollected on age, sex, month-wise distribution of
      various medico legal cases, weapon inflicting the injury, blunt trauma or
      physical assault, firearm injuries and road traffic accidents. The data thus
      obtained was analyzed using SPSS; observations were presented in tables and
      graphs. RESULTS: Out of all 3105 registered medico legal cases, reported cases
      caused by Road Traffic Accident 1230 (40%) followed by blunt injury or physical
      assault 966 (32%) cases, 19% by sharp weapons, 5% by poisoning, and 4% by firearm
      injuries. In our study out of 3105 cases, almost three quarter of victims (73%)
      were below 30 years of age, with a decreasing frequency beyond this age, males
      were predominantly inflicted 2516(81%) as compared to females 589 (19%). The
      reported road traffic accidents cases from urban areas were high (74%) as
      compared to those from rural locality (37%). In cases of blunt trauma, sharp
      weapon injuries and firearm injuries, there was a huge preponderance of victims
      from rural areas (65%), (62%) and 61% respectively, with urban cases constituting
      less. CONCLUSION: Road traffic injuries are one of the foremost causes of medico
      legal cases followed by blunt trauma and sharp weapon injuries. The emerging
      medico legal cases are neglected epidemic in most of the developing countries
      comprising a considerable public health problem.

PMID- 29067068
TI  - Therapeutic benefits of green tea extract on various parameters in non-alcoholic
      fatty liver disease patients.
AB  - BACKGROUND AND OBJECTIVE: NAFLD affecting up to 30% of the population globally.
      Drug treatment options are limited with disappointing results. The dietary
      supplementation in the form of green tea is another option. Our objective was
      toinvestigate the effect of Green tea extract (GTE) supplementation on various
      parameters innon-alcoholicfatty liver disease (NAFLD) patients. METHODS: This
      study was conducted Dept. of Medicineof Sheikh Zayed Medical College/Hospital,
      Rahim Yar Khan from 15 April 2016 to 15 July 2016. Eighty overweight, non
      diabeticand dyslipidemic patients of NAFLD, diagnosed on the basis of ultrasound
      and aminotransferases level were randomized for treatmentwith capsule GTE500mg
      (n=40)and capsule placebo (n=40) twice a day for twelve weeks. Anthropometric
      parameters, liver enzymes, inflammatory markers and liver ultrasound imaging were
      estimated by SPSS-16 pre and post treatment. RESULTS: As compared to placebo, GTE
      caused a significant improvement in body weight (29.5+/-3.8 to 27.2+/-3.2 kg/m2
      p=0.03), BMI (86+/-10.5 to 80+/-12.4 kg p=0.026), HOMA-IR(4.32+/-2.25 to 3.16+/-
      1.6 p=0.0081) lipid profile (i.e. TC: L242.5+/-20.5 to 215.4+/-18.6 mg/dl
      p=0.005; TG: 175+/-22.6 to145+/-18 mg/dlp=0.003; LDL-C:155+/-12.5 to 140+/-16.7
      mg/dl p=0.011; HDL-C: 36.8+/-6.7 to46.4+/-5.8 mg/dl p =0.001, Aminotransferases
      (i.e. ALT: 70.4+/-15.8to52.8+/-12.2 IU/L p=0.04; AST: 65.8+/-12.4 to 44.3+/-
      8.5U/L p =0.002) and Inflammatory markers (hs-CRP: 3.14+/-0.58 to 2.18+/-0.32 p
      =0.023 Adiponectin: 8.46+/-1.02 to 10.55+/-3.42MUg/ml p =0.003)GTE also caused a
      67.5% regression of fatty liver changes on ultrasound as compared to placebo
      which is 25%only. CONCLUSION: GTEtherapy resulted in significant improvement in
      metabolic, chemical, inflammatory and radiological parameters of non-alcoholic
      fatty liver disease patients who were non-diabetic anddyslipidemic.

PMID- 29067069
TI  - Can hematologic parameters predict treatment of ectopic pregnancy?
AB  - OBJECTIVE: Ectopic pregnancy (EP) is the major cause of maternal morbidity and
      mortalityinthe first trimester of pregnancy. EP can be treated either medical or
      surgical approches. The purpose of our study wasto predict the treatment choice
      of tubal EP by usinghematologic parameters which are routinely used in clinical
      practice. METHODS: After retrospectively data evaluation was done from Januaryu
      2014 to Deceber 201. we had 153 patients with EP. Patientsadmitted to
      methotrexate (MTX) therapy was Group-1. Patients performed surgerywas Group-II.
      All patients' initial values including white blood cell (WBC), hemoglobin (Hgb),
      mean corpuscular volume (MCV), neutrophil and lymphocyte, neutrophil lymphocyte
      ratio (NLR), platelet, platelet lymphocyte ratio (PLR), red cell distribution
      width (RDW), platelet distribution width (PDW) and mean platelet volume (MPV)were
      recorded and compared between groups. RESULTS: Of 153 EP patients, there were 93
      patients in MTX group and 60 patients in surgery group. RDW, MPV were
      significantly increased in MTX group (p=0.003, p=0.001, p=0.038, respectively).
      However, no statistically significant difference was observed between the groups
      in terms of WBC, Hgb, MCV, PLT, PLR, PDW. CONSLUSION: RDW, MPV values were
      independently associated with MTX therapy. Hematologic parameters can be helpful
      in the choice of the EP treatment.

PMID- 29067070
TI  - Analysis of renal artery morphometery in adults: A study conducted by using
      Multidetector computed Tomography Angiography.
AB  - OBJECTIVE: To determine a reference range of renal artery measurements by using
      Multidetector Computed Tomography (MDCT) angiography and to find association of
      renal artery measurements with side of artery, gender and age. METHOD: Two
      hundred and fifty study participants without renal artery disease who
      werepresented to Radiology Department, Ziauddin Hospital, Karachi, from November,
      2016 to April, 2017 were included in this study. Main renal artery measurements
      were taken on Multidetector computed angiography and variation with side, gender
      and age were analyzed. Statistical analysis was done on Statistical Package for
      Social Sciences (SPSS) version 20. Independent sample T test, one way ANOVA and
      Pearson's correlation analysis were applied. P-value of < 0.05 was considered
      significant. RESULTS: A significance difference (p=0.001) was seen between mean
      right renal artery (diameter 6.66 +/- 0.39 mm; length 44.69 +/- 2.48 mm) and left
      renal artery (diameter 6.79 +/- 0.36; length 35.10 +/- 2.86 mm). Females found to
      have smaller mean diameter and length of renal arteries than males. However, a
      weak negative correlation was seen between mean renal artery diameter and age
      (right r= -0.158, p=0.0121; left r= -0.017, p= 0.708). CONCLUSION: The mean
      diameter and mean length were found to be significantly different between right
      and left main renal artery and between males and females. A significant weak
      negative correlation was observed between renal artery diameter and age.

PMID- 29067071
TI  - Caries Risk Assessment in School Children Using Reduced Cariogram Model.
AB  - OBJECTIVE: To estimate the percentage of children with low, moderate and high
      caries risk; and to determine the predictors of caries risk amongst 11-12 year
      old Pakistani school children. METHODS: Subjects' caries risk was assessed using
      the Cariogram programme. The survey was done among school children in Bhakkar
      district of Punjab, Pakistan. Caries and plaque level were assessed using the
      DMFT and Sillnes and Loe indices respectively, while diet content and frequency
      were assessed using a three-day diet diary. RESULTS: A total of 226 children
      participated in this study, giving a response rate of 75%. Most subjects (39.8%)
      were in the low risk category with DMFT score of 0. The overall mean DMFT score
      was 1.49 (+/-0.63). Linear and multiple regressions were performed to evaluate
      the predictability of caries risk. Previous experience of dental caries was found
      to be the most relevant predictor of caries risk (40%). CONCLUSION: The levels of
      caries risk amongst Pakistani 11-12 year old school children were generally low.
      Past caries experience was the most significant factor in predicting future
      caries lesion in this sample population.

PMID- 29067072
TI  - Behavioral factors for predicting severity of enuresis and treatment responses in
      different compliance groups receiving behavioral therapy.
AB  - OBJECTIVE: To investigate behavioral factors for predicting severity of nocturnal
      enuresis and compare response rates in different compliance groups of behavioral
      interventions. METHODS: Three hundred eleven children diagnosed with nocturnal
      enuresis were enrolled. This study was conducted at Beijing Children's Hospital
      affiliated to the Capital Medical University from September 2016 to December
      2016. Correlation of severity of enuresis and behavioral factors was
      investigated. All patients were treated with desmopressin based on behavioral
      interventions. After twomonth treatment, the patients were grouped according to
      the compliance of behavioral therapy. Then response rates in different compliance
      groups were compared. RESULTS: Multivariate analysis revealed stool frequency,
      drinking water before going to bed, awaking the child to toilet at night, and
      appetite were independent risk factors affecting the severity of enuresis. The
      complete response rate of enuresis and partial response ratein fullcompliance
      group are higher than thoseof partial compliance and non-compliance group(21.9%
      vs 11.3%, 78.1% vs 59.8%; 21.9% vs 0%, 78.1% vs 49.1%; P<0.01). The complete
      response rate and partial response rate of partial compliance group are higher
      than those of the non-compliance group (P<0.01). CONCLUSIONS: Stool frequency,
      drinking water before going to bed, awaking the child to toilet at night, and
      appetite are independent predictive factors affecting the severity of enuresis.
      Good compliance of behavioral interventions may have a crucial role for better
      therapeutic outcomes.

PMID- 29067073
TI  - Impact of stent length and diameter on short term clinical outcomes of drug
      eluting stents in patients with stable coronary artery disease.
AB  - BACKGROUND & OBJECTIVE: The risk of restenosis and other adverse cardiovascular
      events with bare-metal stents have increased with smaller stent diameters and
      longer stent lengths. However, the exact impact of stent size on the short-term
      outcomes of drug-eluting stent (DES) implantations has not been much classified
      in Pakistani population. This study was designed to evaluate the impact of size
      (length and diameter) of Drug Eluting Stents on Clinical outcomes in patient with
      stable coronary artery disease at three months of implantation in Pakistani
      Population. METHODS: This is a prospective study which was carried out in the
      Department of Cardiology, Lady Reading Hospital Peshawar from April 2011 and July
      2012. All consecutive patients with stable coronary disease undergoing
      Percutaneous Intervention (PCI) with DES implantation at Cardiology Unit Lady
      Reading Hospital, were included prospectively. Clinical outcomes (Myocardial
      infarction [MI], unstable angina[UA], and positive ETT) at three months
      stratified by 3 tertiles of stent length and diameter each, were measured in
      patients who underwent PCI with DES for coronary artery lesions. All patients
      were followed and reassessed after three months from the index procedure.
      Exercise Tolerance Test(ETT) was performed on every patient and recorded on
      proforma. Data analysis was done using SPSS software version 16. RESULTS: A total
      of 376 patients were included prospectively in this study. The mean age was 57+/
      9.313 years. Male patients were 271(72.1%). Mean length of drug eluting stent was
      27.313+/-7.235 mm while mean diameter of stent was 2.90+/-0.2483mm. There were
      slightly higher rates of MI, U.A and positive ETT in the longest stent length
      tertile(>28mm) compared with the shortest stent length tertile (<22mm) at three
      months, but they were statistically not significant. We also observed that for
      DES, there was no clear relationship between stent diameter and outcome for any
      of the clinical outcome variables. CONCLUSION: In our single-center prospective
      study, stent length and diameter defined in tertiles, had no impact on the short
      term clinical outcomes of DES in patients with stable coronary artery disease.

PMID- 29067074
TI  - Profile of hepatic involvement in dengue infections in adult Pakistani
      population.
AB  - OBJECTIVES: To estimate the range of hepatic involvement in dengue infections by
      assessing clinical and biochemical profile of adult dengue infected patients.
      METHODS: Serologically confirmed 220 adult cases of dengue infections admitted to
      Mayo hospital from June 2013 to November 2013 were classified as having dengue
      fever, dengue haemorragic fever and dengue shock syndrome. The frequency and
      range of bilirubin, liver enzymes derangement and presence of liver enlargement
      in each group was calculated and further stratified according to age and gender.
      Patients with positive viral serology, chronic liver disease, malaria and typhoid
      were excluded from the study. RESULTS: About 60% of DHF patients had hepatomegaly
      compared to 40% of DF patients. Liver dysfunction was more common in DF compared
      to DHF (38.15 vs 18.6%). Hyperbilirubinemia was noted in 40 (18.2%) patients, 28
      (12.7%) in DF and 12(5.5%) in DHF. The mean serum bilirubin was higher in DHF
      [0.87+0.33] compared to DF [0.74+0.27]. Bilirubin was higher in male patients and
      in younger (<20 years) age group. ALT was elevated more frequently in male
      patients in age group of 31-40 years and in DF patients as compared to DHF
      [72(32.7% vs 40(18.2%)]. The mean serum ALT level was 103.7 U/l in DHF and
      69.2U/l in DF. AST was raised in all DHF patients as compared to DF in which 40%
      patients had normal AST levels. Alkaline Phosphate was high in all DHF patients
      with a mean of 278.7. It was raised in most of the DF patients as well and
      majority of patients were in age group of 31-40 years. CONCLUSION: Liver
      involvement is very common in dengue infections and is not limited to elevation
      of transaminases only. Bilirubin and Alkaline phosphatase are also raised in
      considerable number of patients. Therefore in adults with fever, jaundice,
      hepatomegaly and altered liver function tests, the diagnosis of dengue infection
      should be strongly considered in areas where dengue infection is endemic. List of
      abbreviations:DF: Dengue Fever DHF: Dengue Hemorrhagic Fever DSS: Dengue Shock
      Syndrome DIC: Disseminated intravascular coagulation ALT: Alanine transaminase
      AST: Aspartate aminotransferase.

PMID- 29067075
TI  - A Chinese family with congenital Dysfibrinogenemia carries a heterozygous
      missense mutation in FGA: Concerning the genetic abnormality and clinical
      treatment.
AB  - OBJECTIVES: Congenital dysfibrinogenemia is a rare hereditary disease
      characterized by normal antigen level but lower function level of fibrinogen.
      Patients with congenital dysfibrinogenemia usually present as bleeding and/or
      thrombotic events. In this study, we explored the genetic abnormality and
      clinical treatment of a Chinese family with dysfibrinogenemia. METHODS: This
      study was conducted in Jan 2015 to Jan 2016 in the Second Medical College
      (Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong Province, P.R.
      China. Coagulation function test were used to screen patients in this family. For
      all family members, DNA from peripheral blood was isolated. Whole-genome exon
      sequencing was carried out to screen possible mutations. And sanger sequencing
      was employed to further confirm the mutation in patients. RESULTS: The proband is
      a woman who had anemia and increased menstruation. Hypofibrinogenemia was found
      after admission. However, a pulmonary embolism occurred after the fibrinogen
      replacement treatment. Whole exon sequencing was conducted afterward. A candidate
      mutation in FGA gene (c.103C>A) was identified and validated in the woman and in
      two siblings. CONCLUSION: From this case, we learned that1) point mutation of
      c.103C>A is the pathogenesis for congenital dysfibrinogemia in this family; 2)
      thromboprophylaxis should always be in consideration when fibrinogen replacement
      is conducted. Prospective studies are needed to determine the best fibrinogen
      replacement strategy in order to achieve adequate hemostasis while minimize risk
      of thrombosis.

PMID- 29067076
TI  - Modifiable cardiovascular risk factors in Rheumatoid Arthritis.
AB  - OBJECTIVE: To determine the frequency of modifiable cardiovascular risk factors
      in Rheumatoid Arthritis patients at tertiary care hospital. METHODS: During this
      study 246 patients of Rheumatoid Arthritis were enrolled from outpatients
      department of Medicine of Central Park Medical College Hospital, Lahore from July
      1, 2016 to January 31, 2017. Demographic data and questions related to study were
      noted. After 14 hours of fasting 5ml of venous blood was drawn for Cholesterol,
      triglycerides, HDL and blood sugar level. Blood tests were performed on COBAS c
      III (ROCHE), Framingham 10 year Risk score was calculated for every individual.
      RESULTS: The mean age of male population was (50.2 +/-7.5) and females (48.4+/
      7.6) and female gender was common. Seventy eight (78%) of study population has
      one modifiable risk factor. Most frequent risk factor found in this study was
      BMI>30 in 48.4% (n=119), High LDL 43.5% (n=107), moderate to high FRS score 40.2%
      (n=99), Hypertension 37.4% (n=92), Diabetes Mellitus was present in 22.8% (n=56),
      while smoking was least frequent risk factors with frequency of 15.9% (n=39).
      Framingham cardiovascular risk score was significantly different, males were
      having higher mean 10 year risk score (19.7%) and females (8.7%) with (p-<0.01).
      Regression analysis revealed that older patients of Rheumatoid Arthritis with
      disease duration of more than seven years are four times more likely to have High
      Framingham risk score, moderate to high LDL and diabetes mellitus with
      significant high Odds ratio (p-value <0.05). CONCLUSION: Rheumatoid Arthritis
      patients are having increased chances of developing cardiovascular risk factors
      leading to cardiovascular events with male sex, increasing age and disease
      duration.

PMID- 29067077
TI  - Do triple test results predict risk for neonatal hyperbilirubinemia?
AB  - OBJECTIVE: Neonatal jaundice is the most common condition that requires hospital
      admission and outpatient follow-up after discharge in neonates. The values of
      more than 17 mg/dL in term infants are accepted as neonatal significant
      hyperbilirubinemia. We aimed to define if there is any relationship between
      second trimester serum markers and neonatal severe hyperbilirubinemia to protect
      the neonates from its neurological damage. METHODS: Total 1372 pregnant women
      were enrolled who had done triple test between April 2014 and 2015 and then given
      birth at our hospital. Our primary outcome was neonatal significant
      hyperbilirubinemia. RESULTS: The mean age of our study population was 27.9+/-5.6.
      A total of 59 patients had babies with neonatal hyperbilirubinemia after
      exclusion of Rh incompatibility. We detected that the presence of in vitro
      pregnancy, maternal health problems or poor obstetric history had no effect on
      the risk for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia was related
      with low E3 levels. The ratios of AFP/E3 and hCG/E3 were the most helpful to
      predict the neonatal hyperbilirubinemia. CONCLUSIONS: According to our results,
      low E3 levels in the triple test result can be helpful to predict the development
      of the neonatal hyperbilirubinemia. However, this is a bit expensive and many
      developing countries may not afford it.

PMID- 29067078
TI  - Tetralogy of Fallot repair in patients presenting after Infancy: A single surgeon
      experience.
AB  - OBJECTIVE: To determine the early surgical outcomes of Tetralogy of Fallot (TOF)
      repair in children and young adults operated after the age of one year. METHODS:
      In this retrospective study, 307 cases of primary repair of Tetralogy of Fallot
      were done between September 2012 to February 2017, at CPE Institute of
      cardiology, Multan. Out of 307 operated patients, 4 (1.3%) patients had previous
      modified Blalock Taussig shunts, 2 (0.6%) associated ASD with TOF, 3 (0.9%) co
      association of TOF with PDA, 2 (0.6%) had large conal arterial branch crossing
      the annulus, 3 (0.9%) had dextrocardia with situs inversus, 12 (3.9%) TOF with
      double outlet right ventricle (DORV), 2 (0.6%) were associated with complete AV
      canal defect, 8 (2.60%) with absent pulmonary valve syndrome, 15 (5.5%) with left
      pulmonary artery stenosis. Data of post-operative complications and operative
      parameters was recorded for all patients. RESULTS: Mean age of operated patients
      was 9.56+/-4.89 years. Post-operative complications occurred in 7.8% of patients.
      Most common post-operative complications were pleural effusion with a frequency
      of 12(3.9%) patients, and complete heart block in one patient. Insignificant
      small residual VSD was diagnosed in 8 (2.6%) patients. One moderately large VSD
      was closed surgically after one year of 1st surgery. Moderate to severe pulmonary
      valve regurgitation was diagnosed in 114 (37.1%) patients. Mild to moderate
      tricuspid regurgitation in 15 (4.8%) patients and moderate right ventricular
      outflow tract obstruction (RVOT) in 16 (5.2%) patients. Thirty-day mortality was
      only four (1.3%). CONCLUSION: Surgical correction of Tetralogy of Fallot (TOF) in
      children after one year carries good operative outcomes with minimum morbidity
      and mortality.

PMID- 29067079
TI  - Tamsulosin and Solifenacin in the Treatment of Benign Prostatic Hyperplasia in
      combination with overactive bladder.
AB  - OBJECTIVE: To analyze the clinical effect of tamsulosin and Solifenacin in the
      treatment of benign prostatic hyperplasia in combination with overactive bladder
      and its safety. Another objective was to investigate the clinical effect and
      safety of mega dose of tamsulosin in the treatment of benign prostatic
      hyperplasia in combination with overactive bladder. METHODS: One hundred and
      twenty-four patients who were admitted to the Dept. of Urology at Binzhou
      People's Hospital, , China with confirmed benign prostatic hyperplasia (BPH) with
      overactive bladder were randomly divided into two groups. Sixty-two patients in
      the control group were treated with tamsulosin, while sixty-two patients in the
      observation group were treated with tamsulosin in combination with solifenacin.
      The treatment of both groups lasted for 12 weeks. The effect and adverse reaction
      were compared between the two groups. RESULTS: The international prostate symptom
      score (IPSS), quality of life (QOL), and overactive bladder symptom score
      (OABSS), Qmax, pulmonary vascular resistance (PVR), daytime urination frequency,
      urgent urination frequency, urge urinary incontinence frequency and night urinary
      frequency of both groups improved after treatment, and the difference had
      statistical significance (P<0.05). The differences of the observation indexes
      (except PVR) in the observation group before and after treatment was
      significantly different with those of the control group (P<0.05). The incidence
      of adverse reactions in the observation group was lower than that in the control
      group, but the difference had no statistical significance (X2=2.843, P>0.05).
      CONCLUSION: Treating benign prostatic hyperplasia in combination with overactive
      bladder with tamsulosin in combination with solifenacin is more effective than
      tamsulosin, without significantly increasing adverse reactions. Thus the therapy
      is worth clinical promotion.

PMID- 29067081
TI  - Budesonide Nebulization in the Treatment of Neonatal Ventilator Associated
      Pneumonia.
AB  - OBJECTIVE: To investigate the clinical effect of budesonide nebulization in the
      treatment of ventilator associated pneumonia of newborns and its safety. METHODS:
      Forty-five newborns who had ventilator associated pneumonia and were admitted
      into the Binzhou People's Hospital between May 2014 and May 2015 were selected
      and included as an observation group. Moreover, another forty-five newborns who
      had ventilator associated pneumonia but did not undergo budesonide treatment in
      2014 were randomly selected and included as a control group. Patients in the
      observation group were given budesonide suspension nebulization in addition to
      the conventional treatment. The evaluation indicators for therapeutic effect were
      compared between the two groups. The changes of head circumference, height and
      weight and death rate were observed by follow up after treatment. RESULTS: The
      mechanical ventilation time, time for recovering from chest X-ray scan and
      hospitalization time of patients in the observation group were shorter than that
      of the control group, and the difference had statistical significance (P<0.05).
      The oxygen index of the patients in the observation group was significantly
      improved compared to that of the control group, and the difference had
      statistical significance (P<0.05). Patients in the two groups were followed up
      for six months after discharge. The head circumference, height and weight of the
      patients in the observation group in the 3rd and 6th month were compared to those
      of the control group, suggesting no significant differences (P>0.05). The
      cumulative death rate of the observation group in the 6th month after treatment
      was significantly lower than that of the control group, and the difference had
      statistical significance (P<0.05). CONCLUSION: Treating ventilator associated
      pneumonia of newborns with budesonide nebulization can effectively shorten
      mechanical ventilation time, time for recovering from chest X-ray scan and
      hospitalization time, improve pulmonary diffusion function and reduce the death
      rate, without affecting the growth and development of patients in the future.

PMID- 29067080
TI  - Incidence and risk factors of Pulmonary Complications after Cardiopulmonary
      bypass.
AB  - OBJECTIVE: To determine the frequency of post-operative pulmonary complications
      (PPCs) after cardio-pulmonary bypass and association of pre-operative and
      intraoperative risk factors with incidence of PPCs. METHODS: This study was an
      observational analysis of five hundred and seventeen (517) patients who underwent
      cardiac surgery using cardiopulmonary bypass. Incidence of PPCs and risk factors
      of PPCs were noted. Logistic regression was applied to determine the association
      of pre-operative and intraoperative risk factors with incidence of PPCs. RESULTS:
      Post-operative pulmonary complications occurred in 32 (6.2%) patients. Most
      common post-operative pulmonary complication was atelectasis that occurred in 20
      (3.86%) patients, respiratory failure in 8 (1.54%) patients, pneumonia in 3
      (0.58%) patients and acute respiratory distress syndrome in 1 (0.19%) patients.
      The main risk factor of PPCs were advance age >= 60 years [odds ratio 4.16 (1.99
      8.67), p-value <0.001], prolonged CPB time > 120 minutes [odds ratio 3.62 (1.46
      8.97) p-value 0.003], pre-op pulmonary hypertension [odds ratio 2.60 (1.18-5.73),
      p-value 0.016] and intraoperative phrenic nerve injury [odds ratio 7.06 (1.73
      28.74), p-value 0.002]. Operative mortality was 9.4% in patients with PPCs and
      1.0% in patients without PPCs (p-value 0.01). CONCLUSION: The incidence of post
      operative pulmonary complications was 6.2% in this study. Advanced age (age >= 60
      years), prolonged CPB time (CPB time > 120 minutes), pre-op pulmonary
      hypertension and intraoperative phrenic nerve injury are independent risk factors
      of PPCs after surgery.

PMID- 29067083
TI  - The long-term prognosis of epilepsy patients with medically treated over a period
      of eight years in Turkey.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of demographic and
      clinical characteristics on temporal changes in seizure control and frequency in
      medically treated epilepsy patients to guide treatment modalities. METHODS: We
      retrospectively analyzed the association between clinical and demographic
      characteristics and seizure frequency in 1329 epilepsy patients who were followed
      up at an outpatient clinic for one to eight years, 2008-2015.. RESULTS: Younger
      age at first seizure (p = 0.0465) and a long disease duration (p = 0.0406) had a
      negative effect on seizure control in all the epilepsy patients. Febrile
      convulsions (FCs) (p > 0.0001), perinatal risk (PNR) (p > 0.0002), a family
      history of epilepsy (FHE) (p > 0.0016), antiepileptic drug (AED) use (p > 0.001),
      mental retardation (MR) (p > 0.001), and psychiatric disorders (p > 0.0478) were
      prognostic indictors of temporal changes in seizure frequency. The presence of
      PNR (p = 0.0416), age at onset of epilepsy (p = 0.034), central nervous system
      infection (CNSI) (p = 0.04), and AEDs number (p = 0.0282) were prognostic
      indicators of not remaining seizure free for one year. In those with partial
      epilepsy, a trauma history (p = 0.05), a longer epilepsy duration (p = 0.0057),
      and FHE (p = 0.0466) increased the frequency of seizures, whereas cerebrovascular
      event (CVE) history decreased the seizure frequency (p = 0.0413). In addition,
      FHE (p = 0.0438) and psychotic disorders (p = 0.0416) increased generalized
      seizures frequency. CONCLUSION: In all the epilepsy patients, a younger age at
      onset and longer duration of epilepsy were associated with a poor prognosis. The
      presence of PNR, age at onset of epilepsy, CNSI, and AEDs numbers were prognostic
      indicators of not remaining seizure free for one year. Increasing AEDs number was
      not effective in controlling seizures in partial epilepsy, but it was effective
      in controlling seizures in generalized epilepsy.

PMID- 29067082
TI  - Effectiveness of core stabilization exercises and routine exercise therapy in
      management of pain in chronic non-specific low back pain: A randomized controlled
      clinical trial.
AB  - BACKGROUND & OBJECTIVE: Low back pain is a frequent problem faced by the majority
      of people at some point in their lifetime. Exercise therapy has been advocated an
      effective treatment for chronic low back pain. However, there is lack of
      consensus on the best exercise treatment and numerous studies are underway.
      Conclusive studies are lacking especially in this part of the world. Thisstudy
      was designed to compare the effectiveness of specific stabilization exercises
      with routine physical therapy exerciseprovided in patients with nonspecific
      chronic mechanical low back pain. METHODS: This is single blinded randomized
      control trial that was conducted at the department of physical therapy Orthopedic
      and Spine Institute, Johar Town, Lahore in which 120 subjects with nonspecific
      chronic low back pain participated. Subjects with the age between 20 to 60 years
      and primary complaint of chronic low back pain were recruited after giving an
      informed consent. Participants were randomly assigned to two treatment groups A &
      B which were treated with core stabilization exercise and routine physical
      therapy exercise respectively. TENS and ultrasound were given as therapeutic
      modalities to both treatment groups. Outcomes of the treatment were recorded
      using Visual Analogue Scale (VAS) pretreatment, at 2nd, 4th and 6th week post
      treatment. RESULTS: The results of this study illustrate that clinical and
      therapeutic effects of core stabilization exercise program over the period of six
      weeks are more effective in terms of reduction in pain, compared to routine
      physical therapy exercise for similar duration. This study found significant
      reduction in pain across the two groups at 2nd, 4th and 6th week of treatment
      with p value less than 0.05. There was a mean reduction of 3.08 and 1.71 on VAS
      across the core stabilization group and routine physical therapy exercise group
      respectively. CONCLUSION: Core stabilization exercise is more effective than
      routine physical therapy exercise in terms of greater reduction in pain in
      patients with non-specific low back pain.

PMID- 29067084
TI  - Value of HE4 Combined with Cancer Antigen 125 in the Diagnosis of Endometrial
      Cancer.
AB  - OBJECTIVE: To investigate the clinical significance of human epididymal secretory
      protein E4 (HE4) in combination with cancer antigen 125 (CA125) in the diagnosis
      of endometrial cancer. METHODS: One hundred and fifty patients with endometrial
      cancer who were admitted to Binzhou People's Hospital, Shandong, China, between
      June 2013 and July 2014, were enrolled and set as an endometrial cancer group;
      another one hundred patients with benign uterine diseases and one hundred healthy
      females were also enrolled. The serum was collected from the subjects for the
      detection of HE4 level. The level of CA125 was detected using
      electrochemiluminescence assay (ELISA). Receiver Operating Characteristic (ROC)
      curve was drawn to analyze the cutoff points of HE4 and CA125 levels for the
      diagnosis of endometrial cancer. The diagnostic efficacy based on the detection
      of the two indexes separately and jointly was evaluated. RESULTS: The area under
      curve (AUC) for diagnosis of endometrial cancer based on HE4 was superior to that
      based on CA125 (0.819 vs 0.757). The optimal diagnosis cutoff point of HE4 and
      CA125 on the ROC curves was 92.21 pmol/L and 31.32KU/L, respectively. The
      sensitivity, Youden index, coincidence rate and negative predicted value of
      diagnosing endometrial cancer with HE4 in combination with CA125 (73.2%, 0.641,
      83.5% and 83.4%) were significantly higher than those of diagnosing endometrial
      cancer with the two indexes separately. The ROC-AUC value of serum HE4 and CA125
      was 0.749 and 0.528 respectively, much lower than that of HE4 in combination with
      CA125 (0.794; P<0.05). CONCLUSION: Serum HE4 and CA125 are the ideal marker
      combination for the diagnosis of endometrial cancer. HE4 combined with CA125 is
      beneficial to the diagnosis of endometrial cancer; hence it is worth promotion in
      clinical practice.

PMID- 29067085
TI  - Two cases about mesh adhesion to intra-abdominal cavity tissue after using mesh
      to repair an incisional hernia.
AB  - Abdominal incisional hernia is a common postoperative complication. With the
      development of a new type of surgical anti-adhesion mesh, mesh repair has become
      a widely-adopted procedure, particularly in the laparoscopic era. However, there
      were few reports about use of these new meshes to repair incisional hernia in the
      abdominal cavity. In this report, we present two cases: one a 72-year-old male
      and the other a 62-year-old female. Both of those patients suffered incisional
      hernias during abdominal operations, and therefore underwent open incisional
      hernia anti-adhesion mesh repair operations. Both of them had recurrent
      incisional hernias after the first repair operation. During the second hernia
      repair operation via laparoscopy, tissue from the intestine and omentum were
      found to have adhered seriously to the old meshes, which could cause many serious
      problems. We need to pay more attention to the issue of adhesion, try to
      determine possible reasons and improve in our future work.

PMID- 29067087
TI  - Effectiveness of interventions for pain relief in hysterosalpingographyAnetwork
      meta-analysis and systematic review.
AB  - OBJECTIVE: We aimed to evaluate the effectiveness of placebo, oral opioid
      analgesic (OOA), intravenous opioid analgesic (IOA), non-opioid analgesic (NOA),
      topical anesthetic (TA) and locally injected anesthetic (LIA) for pain relief
      duringhysterosalpingography (HSG) using a Bayesian network meta-analysis of data
      from randomized controlled trials. METHODS: PUBMED, EMBASE, and CENTRAL search
      engines were used to search and identify clinical trials that evaluated
      interventions for pain relief in HSG. Methodological studies quality was assessed
      by the Cochrane Collaboration tool for assessing risk of bias. RESULT: Sixteen
      trials involving 1263 participants were included in this study. IOA got excess
      but not statistically significant lower visual analogue score (VAS) pain score
      during HSG or more than 30 minutes after HSG compared with the other groups. OOA
      resulted in excess but not statistically significant higher VAS pain score during
      HSG compared with the other groups except placebo group. According to SUCRA
      regarding the lower VAS pain score during HSG, the treatments rank was the
      following: IOA, TA, NOA, LIA, OOA and placebo; as regard lower VAS pain score at
      30 minutes or more after HSG, the treatments rank was the following: IOA, LIA,
      OOA, TA, NOA and placebo. CONCLUSION: This new Bayesian data network meta
      analysis from randomized controlled trials demonstrated that IOA resulted in the
      highest probability to reduce the pain during HSG or at 30 minutes or more after
      HSG among the six interventions considered.

PMID- 29067086
TI  - The effect of omega-3 unsaturated fatty acids on non-alcoholic fatty liver
      disease: A systematic review and meta-analysis of RCTs.
AB  - OBJECTIVE: During the treatment of diseases such as angiocardiopathy, blood lipid
      abnormalities and metabolic syndrome, omega-3 unsaturated fatty acids (PUFA) can
      reduce plasma lipids and improve cardiovascular status, thus ameliorating disease
      severity. We aimed to explore the effects of PUFA supplementation in patients
      with non-alcoholic fatty liver disease (NAFLD). METHODS: A systematic literature
      search was performed during March 2016 for randomized controlled trials using
      PUFA or fish oil supplementation in patients with NAFLD or non-alcoholic
      steatohepatitis (NASH). All Randomized controlled trials were retrieved from
      MEDLINE and EMBASE database up to date (March 2016). A meta-analysis of key
      outcomes (serum level of liver enzymes and lipids) were identified in these
      studies. The mean difference (MD) and the corresponding 95% confidence intervals
      (CIs) were used as measures of effect size. RESULTS: Thirteen studies were
      included, consisting of 266 patients in the PUFA group and 402 cases in the
      control group. Serum level of alanine aminotransferase (ALT) was lower in the
      PUFA group than that in in the controls [MD=-9.18, 95% CI (-12.41, -5.96), P
      <0.00001]. However, PUFA treatment did not affect aspartate aminotransferase
      (AST) [MD=-5.07, 95% CI (-12.65, 2.51), P= 0.19], gamma-glutamyl transferase
      (GGT) [MD=-1.91, 95% CI (-4.15, 0.33), P <0.009]. CONCLUSIONS: PUFA
      supplementation may affects serum level of ALT and improve liver function in
      patients with NAFLD.

PMID- 29067088
TI  - Ethical issues in managing Lysosomal storage disorders in children in low and
      middle income countries.
AB  - The lysosomal storage diseases are a group of rare, inherited metabolic diseases
      affecting about 1 in 7000 to 8000 people. In recent years, the introduction of
      enzyme replacement therapy, substrate reduction therapy and small molecule
      therapy, has changed the natural course of this otherwise progressive group of
      disorders leading to severe morbidity and early mortality. These treatment
      options, however, are extremely expensive and are needed for life thus presenting
      an economical as well as ethical challenge to the affected families and the
      health care system of a country. This paper presents a case for the prevention of
      the lysosomal storage disorders as a model for other inherited metabolic
      disorders in the form of antenatal testing and cascade screeningfor couples and
      families at risk of having affected off-springs and compares it to the cost
      incurred on the enzyme replacement therapy in the backdrop of the health care
      prioritiesof Pakistan, a low middle income country. Similar economic and ethical
      challenges are faced by most low and middle income countries. The literature
      search was done using Pubmed and Clinical trials databases using key words:
      "Lysosomal storage disorders", "natural course", "ethics", "cascade screening",
      "Thalassemia" and "cascade screening". A total of 225 articles in English
      language were scanned from 1980-2016, 80 articles describing the natural course
      of LSD with and without ERT, ethical issues related to the treatment of LSD and
      strategies employed for the prevention of genetic disorders were prioritized.

PMID- 29067089
TI  - Is biological repair of heart on the horizon?
AB  - The stem cells keep us young by endogenously repairing us upon need. They do so
      bysmartly one step forward towards differentiation while another step backward to
      nurturethe undifferentiated stem cells. They are building blocks for every organ
      witha differential rate of repair of worn out tissues. Since stem cells can be
      cultured with a normal karyo type, they could be the ideal source for heart
      repair after myocardial infarction. As opposed to lower vertebrates and neonatal
      mice, cardiac regeneration in adult mammalian heart seems to be difficult to
      assess with a solid evidence of cytokinesis. It becomes more difficult to
      quantify the level of regeneration after myocardial infarction injury against a
      background of a large invasion of proliferating inflammatory cells. The question
      to beraised is how the renewal of a piece of myocardium follows the time line of
      picking upcell types in series: cardiomyocytes, endothelial cells, smooth muscle
      cells, fibroblast, pacemaker cells, conducting and Purkinje cells to bring the
      orchestration of rhythmically contracting and relaxing heart. This review focuses
      on where we are onthe status of heart repair and cardiac regeneration.

PMID- 29067090
TI  - A rare case of Ralstonia mannitolilytica infection in an end stage renal patient
      on maintenance dialysis during municipal water contamination.
AB  - Ralstonia mannitolilytica is a gram negative soil bacterium. Ralstonia infection
      though rare, has become the emerging nosocomial pathogens in hospital settings.
      Various clinical manifestations had been described as well as the mode of
      transmission. Despite its low virulence factor, it is able to survive under harsh
      condition and this may potentially cause significant morbidity and mortality
      especially in immunocompromised patients. Outbreak of Ralstonia mannitolilytica
      infections in the hospital are typically associated with contaminated medical
      supplies or instruments. We described here a case of Ralstonia mannitolilytica
      infection in a dialysis patient that occurred during the municipal reservoir
      water contamination crisis. In this report, we will also describe the behaviour
      of Ralstonia genus and its 4 main species, namely R. pickettii, R. solanacearum,
      R. insidiosa, and R. mannitolilytica and the choices of antibiotic therapy based
      on literature review.

PMID- 29067091
TI  - Identifying key genes in glaucoma based on a benchmarked dataset and the gene
      regulatory network.
AB  - The current study aimed to identify key genes in glaucoma based on a benchmarked
      dataset and gene regulatory network (GRN). Local and global noise was added to
      the gene expression dataset to produce a benchmarked dataset. Differentially
      expressed genes (DEGs) between patients with glaucoma and normal controls were
      identified utilizing the Linear Models for Microarray Data (Limma) package based
      on benchmarked dataset. A total of 5 GRN inference methods, including Zscore,
      GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation
      coefficient with Information Theory (PCIT) and GEne Network Inference with
      Ensemble of Trees (Genie3) were evaluated using receiver operating characteristic
      (ROC) and precision and recall (PR) curves. The interference method with the best
      performance was selected to construct the GRN. Subsequently, topological
      centrality (degree, closeness and betweenness) was conducted to identify key
      genes in the GRN of glaucoma. Finally, the key genes were validated by performing
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total
      of 176 DEGs were detected from the benchmarked dataset. The ROC and PR curves of
      the 5 methods were analyzed and it was determined that Genie3 had a clear
      advantage over the other methods; thus, Genie3 was used to construct the GRN.
      Following topological centrality analysis, 14 key genes for glaucoma were
      identified, including IL6, EPHA2 and GSTT1 and 5 of these 14 key genes were
      validated by RT-qPCR. Therefore, the current study identified 14 key genes in
      glaucoma, which may be potential biomarkers to use in the diagnosis of glaucoma
      and aid in identifying the molecular mechanism of this disease.

PMID- 29067092
TI  - Effect of tendon hydrogel on healing of tendon injury.
AB  - Hand trauma arising from postoperative acute or chronic tendon injuries leads to
      delayed union and is one of the greatest challenges in clinical practice. The
      present study hypothesized that an extracellular matrix hydrogel made from
      tendons can promote tendon healing and improve tissue regeneration. To verify
      this, 36 Wistar rats were subjected to bilateral full-thickness injury of their
      Achilles tendons, starting from the heel bone along the center line to remove a
      segment of 5 mm in length and 0.5 mm in width. On the sites of injury, hydrogel
      was injected on one side, while the contralateral side was injected with an equal
      volume of normal saline. At 2, 4 and 8 weeks after the operation, bilateral
      tendons were subjected to biomechanical tests to determine the ultimate failure
      load, tensile strength and toughness, and cross-sectional slices of the tendons
      were subjected to histological analysis. The results indicated that after 2
      weeks, the hydrogel and control group showed no significant difference in terms
      of ultimate load (P=0.15) ultimate tensile stress (P=0.42) and toughness
      (P=0.76). At 4 weeks following surgery, the failure load in the hydrogel group
      was significantly higher than that in the control group (74.8+/-14.2 vs. 58.4+/
      11.6; P=0.02), while there were no significant differences in the ultimate
      tensile stress (P=0.63) and toughness (P=0.08). At 8 postoperative weeks, the
      abovementioned parameters showed no significant difference between the groups
      (P=0.15, 0.39 and 0.75, respectively). In conclusion, the tendon-derived
      extracellular matrix hydrogel was able to significantly improve tendon strength
      at 4 weeks after injury in terms of increasing the ultimate failure load.
      Hydrogel applied immediately after tendon injury can enhance the type-I collagen
      content. The present study therefore provided a basis for further exploration of
      the application of extracellular matrix hydrogel to promote tendon healing in the
      clinic.

PMID- 29067093
TI  - Stent retriever thrombectomy combined with local thrombolytic therapy for
      cerebral venous sinus thrombosis: A case report.
AB  - The present study reports the effect of successful treatment of cerebral venous
      sinus thrombosis (CVST) with stent retriever thrombectomy combined with local
      thrombolytic therapy. Medical records of 29 patients were retrospectively
      analyzed following a diagnosis of CVST with magnetic resonance venography (MRV)
      or digital subtraction angiography (DSA). Systemic anticoagulation was the
      initial treatment in all patients following admission. In group A, stent
      retriever thrombectomy combined with local thrombolytic therapy was performed on
      14 patients who met the criteria of endovascular therapy. Stent-assisted
      angioplasty was also performed when patients presented with venous sinus
      stenosis. A total of 15 patients in group B received systemic anticoagulant
      treatment. Subsequently, warfarin was administered orally for 3 to 12 months as a
      continuous anticoagulant therapy. International normalized ratio was monitored
      when patients were receiving anticoagulant therapy. Additionally, clinical
      presentation, decision to escalate therapy, recanalization, Glasgow Coma Scale,
      modified Rankin Scale (mRS) and the clinical outcome was assessed. A total of 14
      patients (9 female patients, 5 male patients), with ages ranging from 17 to 57
      years, met the criteria of endovascular therapy. The clinical symptoms of 12
      patients had improved after receiving endovascular therapy and only 2 patients
      suffered from intracranial hemorrhage following the procedure. Complete
      recanalization of venous sinus was exhibited in 10/14 (71.4%) patients in group A
      when compared with 1/15 (6.7%) patients in group B. mRS were improved in the 12
      month follow-up in groups A and B when compared with that at admission. In the
      present study, patients with acute CVST treated with stent retriever thrombectomy
      combined with local thrombolytic therapy had a favorable outcome. To conclude,
      the present study provides a treatment option in treating CVST, particularly for
      patients that present with evident cortical venous outflow stasis or deteriorate
      neurology, despite appropriate anticoagulant therapy.

PMID- 29067094
TI  - Dasatinib and chemotherapy in a patient with early T-cell precursor acute
      lymphoblastic leukemia and NUP214-ABL1 fusion: A case report.
AB  - The present study aimed to evaluate the therapeutic efficacy of dasatinib in a
      patient with nucleoporin 214-tyrosine protein kinase ABL1 proto-oncogene 1
      (NUP214-ABL1)-positive early T-cell precursor-acute lymphoblastic leukemia (ETP
      ALL), as well as that of selinexor and dasatinib for NUP214-ABL1-positive ETP-ALL
      in vitro. ETP leukemia is a form of T-cell ALL (T-ALL) with poor prognosis. The
      NUP214-ABL1 gene is present in ~6% of T-ALL cases, however the prevalence of
      NUP214-ABL1 gene expression in ETP-ALL in particular has not yet been verified.
      The current study reports the rare case of a 29-year-old man with ETP-ALL
      harboring the NUP214-ABL1 fusion gene, presenting with low-grade fever,
      stomachache and splenomegaly. The patient was successfully treated with dasatinib
      and vincristine, idarubicin, cyclophosphamide and prednisone (VICP) chemotherapy.
      The therapeutic efficacy of selinexor and dasatinib was also evaluated in vitro.
      Apoptosis was analyzed using Annexin V/propidium iodide staining and flow
      cytometry, and poly ADP-ribose polymerase (PARP) cleavage was detected using
      western blot analysis. The results demonstrated that the apoptotic cell
      population significantly increased following selinexor or dasatinib treatment
      compared with the control (P<0.05). Furthermore, combined selinexor and dasatinib
      treatment led to a significant increase in cell apoptosis compared with either
      treatment alone (P<0.05). The apoptosis results were confirmed by PARP cleavage.
      Thus, NUP214-ABL1 fusion gene expression should be tested in T-ALL, including ETP
      ALL. Dasatinib used in combination with traditional induction chemotherapy may
      reverse the high induction failure of ETP-ALL with NUP214-ABL1 fusion gene;
      however, further prospective studies are required to confirm this. Therefore,
      selinexor with or without dasatinib may serve as a potential salvage therapy in
      the case of relapse and may be developed as a novel treatment for ETP-ALL with
      the NUP214-ABL1 fusion gene.

PMID- 29067095
TI  - Bio-Oss(r) modified by calcitonin gene-related peptide promotes osteogenesis in
      vitro.
AB  - Bio-Oss(r) and alpha-calcitonin gene-related peptide (CGRP) are involved in
      osteogenesis. However, it has remained to be assessed how alpha-CGRP affects the
      effect of Bio-Oss. In the present study, primary osteoblasts were incubated with
      alpha-CGRP, Bio-Oss, alpha-GGRP-Bio-Oss or mimic-alpha-CGRP. The proliferation
      rate, mineralization nodules, alkaline phosphatase (ALP) activity and the
      expression of osteogenic genes were measured by a Cell Counting Kit-8 assay,
      Alizarin Red-S staining, ALP activity detection and reverse-transcription
      quantitative PCR as well as western blot analysis, respectively. The
      proliferation rate, ALP activity and the number of mineralization nodules were
      significantly increased in the alpha-CGRP-modified Bio-Oss group compared to that
      in the Bio-Oss group. The mRNA and protein levels of osteocalcin, Runt-related
      transcription factor-2 and ALP were significantly upregulated in the alpha-CGRP
      Bio-Oss group compared with those in the Bio-Oss group. Furthermore, the effect
      of mimic-alpha-CGRP on osteogenesis was reduced as it carried a mutation. In
      conclusion, the present study was the first to demonstrate that Bio-Oss modified
      with CGRP contributed to osteogenesis and may provide a novel formulation applied
      in the clinic for restoration of large bone defects.

PMID- 29067096
TI  - Adrenomedullin inhibits osteoclast differentiation through the suppression of
      receptor activator of nuclear factor-kappaB ligand-induced nuclear factor-kappaB
      activation in glucocorticoid-induced osteoporosis.
AB  - The current study aimed to improve the understanding on the association between
      adrenomedullin and osteoporosis in mice with glucocorticoid-induced osteoporosis.
      Bone resorption and osteoporosis-associated indexes, including maximum load,
      stiffness, energy to failure, ultimate strength, elastic modulus, post-yield
      displacement and post-yield displacement, in mice with osteoporosis were analyzed
      in order to evaluate the effect of adrenomedullin. The receptor activator of
      nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was
      investigated subsequent to treatment with adrenomedullin in vitro. The results
      demonstrated that adrenomedullin significantly improved bone mass loss, density,
      bone strength and osteoporosis disease in the mice with glucocorticoid-induced
      osteoporosis. In addition, adrenomedullin markedly improved the osteoporosis
      associated NFATc1, TRAP, OSCAR and c-Fos expression levels. Furthermore, the
      current findings indicated that RANKL-mediated osteoclast differentiation was
      suppressed in vitro and in vivo. Notably, the data revealed that adrenomedullin
      significantly improved the osteoporotic symptoms through inhibition of RANKL
      induced NF-kappaB activation in glucocorticoid-induced osteoporosis. In
      conclusion, adrenomedullin serves an essential role in the progression of
      glucocorticoid-induced osteoporosis, regulating the bone mass loss, density and
      strength through the NF-kappaB signaling pathway.

PMID- 29067097
TI  - Highly pathogenic avian influenza A virus H5N1 non-structural protein 1 is
      associated with apoptotic activation of the intrinsic mitochondrial pathway.
AB  - Outbreaks of avian influenza A (H5N1) virus infection have significant health and
      economic consequences. Non-structural protein 1 (NS1) is an essential virulence
      factor of the highly pathogenic H5N1 avian influenza virus and of the apoptosis
      associated with the pathogenesis of H5N1. Previous studies have revealed that the
      NS1 protein is able to induce apoptosis via an extrinsic pathway. However, it
      remains unclear whether the intrinsic pathway is also associated with this
      apoptosis. The present study used a clone of the NS1 gene from avian influenza
      A/Jiangsu/1/2007 and observed the localization of the NS1 protein and cytochrome
      c release from mitochondria and the change of mitochondrial membrane potential
      (MMP) in lung cancer cells. Cytotoxicity was detected using an MTT assay and the
      number of apoptotic cells was counted using a flow cytometer. Following the
      isolation of mitochondria, western blotting was performed to compare cytochrome c
      release from the mitochondria in cells before and after apoptosis. The change of
      MMP was detected using JC-1 staining. Furthermore, the results reveal that the
      majority of the NS1 protein was localized in the cell nucleus, and that it may
      induce apoptosis of human lung epithelial cells. The apoptosis occurred with
      marked cytochrome c release from mitochondria and a change of the MMP. This
      indicated that the NS1 protein may be associated with apoptosis induced by an
      intrinsic mitochondrial pathway.

PMID- 29067098
TI  - Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia
      reperfusion injury in rats.
AB  - The aim of the present study was to observe the dynamic changes of the growth
      arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain
      tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of
      curcumin pretreatment. A total of 60 rats were randomly divided into the normal
      group (N), the sham operation group (S), the dimethyl sulfoxide control group (D)
      and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72
      h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of
      GADD153 and caspase-12 in the brain tissue were detected and compared among the
      groups by immunohistochemistry, immunofluorescence double staining and western
      blotting. The expression levels of GADD153 and caspase-12 were increased at
      T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in
      group D, while GADD153 was increased until T3 in group D. Compared with group D,
      the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were
      significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the
      pathological process of CIRI. Curcumin may decrease the expression levels of the
      above two factors, thus exhibiting protective effects against CIRI in rats.

PMID- 29067099
TI  - Treatment of gout combined with Kienbock's disease: A case report.
AB  - Cases of Kienbock's disease combined with gout are rare; to the best of our
      knowledge, the current report is the third such case reported in the literature.
      The current report presents the case of a 49-year-old male patient with
      Kienbock's disease combined with gout. The patient had experienced swelling and
      pain of their right wrist for 1 month. Through a combination of clinical history,
      physical examination, laboratory results, radiological and intraoperative
      findings, the patient was diagnosed with stage IIIB-IV Kienbock's disease and
      gout. The patient recovered well following a synovectomy and medication for gout.
      The rarity of the present case makes it difficult to examine the potential
      association between gout and Kienbock's disease. Kienbock's disease combined with
      gout tends to be ignored and is easily misdiagnosed. However, the surgical
      procedure selection for Kienbock's disease combined with gout is markedly
      different from the conventional surgery for Kienbock's disease or gout alone. The
      current study outlines a successful treatment strategy for gout combined with
      Kienbock's disease.

PMID- 29067100
TI  - The protective effects of ischemic preconditioning on rats with renal ischemia
      reperfusion injury and the effects on the expression of Bcl-2 and Bax.
AB  - The aim of the present study was to investigate the protective effects of
      ischemic preconditioning on rats with renal ischemia-reperfusion injury and the
      effects on the expression of Bcl-2 and Bax. Thirty-six SD rats were randomly
      divided into three groups (n=12) including sham operation (S) group, ischemia
      reperfusion group (I/R) group and ischemic preconditioning (IP) group. After
      anesthesia with intraperitoneal injection of chloral hydrate, bilateral renal
      pedicles were clipped for 45 min, followed by perfusion for 6 h to establish the
      I/R model. Both kidneys in rats of S group were separated and exposed for 45 min,
      but renal pedicles were not clipped. In IP group, bilateral renal pedicles were
      clipped for 5 min, followed by perfusion for 5 min, this procedure was repeated 3
      times. Then bilateral renal pedicles were clipped for 45 min, followed by
      perfusion for 6 h. Blood samples were collected and rats were sacrificed to
      collect renal tissue. Levels of serum creatinine (Cr) and blood urea nitrogen
      (BUN) were measured. Activity of superoxide dismutase (SOD) was measured by
      xanthine oxidase assay. Degree of renal injury was evaluated by H&E staining.
      TUNEL kit was used to detect the number of apoptotic cells in renal tissue.
      Expression levels of Bcl-2 and Bax were detected by semi-quantitative PCR and
      western blot analysis at mRNA and protein levels, respectively. Results showed
      that levels of Cr and BUN in I/R and IP groups were significantly higher than
      those in S group, and levels of Cr and BUN in I/R group were significantly higher
      than that in IP group (P<0.05). Activity of SOD in I/R group and IP group were
      significantly lower than those in S group, and activity of SOD in I/R group were
      significantly lower than those in IP group (P<0.05). H&E staining showed that,
      compared with S group, renal injury in the I/R and IP groups was more serious
      than that in the S group, and I/R group was more serious than the IP group
      (P<0.05). TUNEL apoptosis assay showed that number of apoptotic cells in IP and
      I/R groups were significantly higher than that in the S group (P<0.01). Semi
      quantitative PCR and western blot analysis showed that, compared with the S
      group, expression levels of Bcl-2 mRNA and protein were significantly decreased,
      expression levels of Bax mRNA and protein were significantly increased, and the
      ratio of Bcl-2/Bax was significantly decreased in the IP and I/R groups (P<0.01).
      Compared with the I/R group, expression level of Bcl-2 was significantly
      increased, the level of Bax was significantly deceased, and the ratio of Bcl
      2/Bax was significantly increased in the IP group (P<0.01). As a result, ischemic
      preconditioning can protect rats with renal ischemia-reperfusion injury possibly
      by increasing the expression level of Bcl-2 and decreasing the expression level
      of Bax.

PMID- 29067101
TI  - Comparison of the effects of minimally invasive percutaneous pedicle screws
      osteosynthesis and open surgery on repairing the pain, inflammation and recovery
      of thoracolumbar vertebra fracture.
AB  - We compared the clinical effects of minimally invasive percutaneous pedicle
      screws osteosynthesis (MIPPSO) and open surgery on the repair of thoracolumbar
      vertebra fracture. Seventy patients, who suffered from thoracolumbar vertebra
      fracture and received treatment at our hospital, were selected and randomly
      divided into either the minimally invasive percutaneous pedicle screws
      osteosynthesis group (MIPPSO group) and the traditional open pedicle screws
      osteosynthesis group (TOPSO group) with 35 cases in each group. The perioperative
      parameters including length of incision, duration of operation, bleeding during
      operation, length of hospital stay, the changes of pre-operative and post
      operative VAS pain scores, inflammatory indexes including serum C-reactive
      protein (CRP) and creatine kinase (CK), and imaging indexes including Cobb's
      angle and anterior margin height of vertebral body of both groups were compared.
      The length of incision, duration of operation, bleeding volume during operation
      and length of hospital stay in the MIPPSO group were significantly lower than
      those in the TOPSO group (P<0.05). Both minimally invasive surgery and
      traditional surgery effectively alleviated the pain (P<0.05), which was more
      significant in MIPPSO group (P<0.05). The post-operative inflammatory indexes,
      CRP and CK levels, of both groups were higher compared to the pre-operation
      (P<0.05), which was more significant in TOPSO group (P<0.05). The differences of
      imaging indexes, including Cobb's angle and anterior margin height of injured
      vertebra, were statistically significant between pre-operation and post-operation
      for each group (P<0.05); however, there were no statistically significant
      differences between two groups at either pre-operation or post-operation
      (P>0.05). The effect of minimally invasive percutaneous pedicle screws
      osteosynthesis is similar to the traditional open surgery, however, the MIPPSO
      technique has the advantages of small trauma, less bleeding, short duration of
      operation, rapid post-operative recovery, light pain, less economic cost, and
      better aesthetic effect and is therefore worthy of clinical promotion.

PMID- 29067102
TI  - Growth/differentiation factor-5 promotes in vitro/vivo periodontal specific
      differentiation of induced pluripotent stem cell-derived mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) derived from induced pluripotent stem cells (iPSCs)
      represent a promising alternative source of MSCs for effective periodontal
      regeneration. Scientific evidence has demonstrated that growth/differentiation
      factor-5 (GDF-5) supports regeneration of periodontal tissues and has a key role
      in MSC differentiation. The present study investigated the effects of recombinant
      human GDF-5 (rhGDF-5) on periodontal specific differentiation of iPSC-derived
      MSCs (iPSC-MSCs) and bone marrow mesenchymal stem cells (BMSCs). rhGDF-5
      treatment in vitro significantly enhanced the expression levels of marker genes
      associated with osteogenesis (OCN), fibrogenesis (periostin) and cementogenesis
      (CAP) in the iPSC-MSCs compared with untreated controls (all P<0.05).
      Interestingly, the rhGDF-5-treated BMSCs failed to exhibit overexpression of
      periostin and CAP despite highly upregulated expression of OCN. In the presence
      of rhGDF-5, both the iPSC-MSCs and BMSCs demonstrated marked formation of
      mineralized nodules. Notably, rhGDF-5 greatly promoted periodontal specific
      differentiation of the iPSC-MSCs encapsulated in hyaluronic acid (HA) hydrogels
      in vivo as determined by immunohistochemical and immunofluorescence staining. The
      majority of the PKH67-labeled iPSC-MSCs implanted with rhGDF-5 exhibited strong
      expression of OCN, periostin and CAP. In conclusion, iPSC-MSCs demonstrate high
      periodontal specific differentiation potential in response to rhGDF-5 both in
      vitro and in vivo. The delivery of iPSC-MSCs and rhGDF-5 with HA hydrogel may
      have beneficial effects in regenerative periodontal therapy.

PMID- 29067103
TI  - Magnetic resonance spectroscopy for assessment of brain injury in the rat model
      of sepsis.
AB  - The diagnostic value of magnetic resonance spectroscopy (MRS), T2-weighted
      imaging (T2WI) and serum markers of brain injury in a rat model of sepsis were
      investigated. Rats were randomly divided into the control group and 6, 12 and 24
      h after lipopolysaccharide-injection groups. Brain morphology and metabolism were
      assessed with T2WI magnetic resonance imaging (MRI) and MRS. Serum and brain
      tissue samples were then collected to examine the concentrations of neuron
      specific enolase (NSE) and S100-beta protein. Brain T2WI showed no differences
      between the groups. N-acetylaspartate/choline (NAA/Cr) ratio measured by MRS
      showed different degrees of decrease in the sepsis groups, and serum NSE and S100
      beta concentrations were increased compared with the control group. Apoptosis
      rates were measured in the right hippocampal area, and there were statistically
      significant differences between the indicated groups and the control group
      (p<0.05). The correlation between apoptosis rate and NAA/Cr ratio was closer than
      that between apoptosis rate and NSE or S100-beta (-0.925 vs. 0.434 vs. 0.517,
      respectively). In conclusion, MRS is a sensitive, non-invasive method to
      investigate complications of brain injury in septic rats, which may be utilized
      for the early diagnosis of brain injury caused by sepsis.

PMID- 29067104
TI  - Isolation and characterization of human umbilical cord-derived endothelial colony
      forming cells.
AB  - Endothelial colony-forming cells (ECFCs) are a population of endothelial
      progenitor cells (EPCs) that display robust proliferative potential and vessel
      forming capability. Previous studies have demonstrated that a limited number of
      ECFCs may be obtained from adult bone marrow, peripheral blood and umbilical cord
      (UC) blood. The present study describes an effective method for isolating ECFCs
      from human UC. The ECFCs derived from human UC displayed the full properties of
      EPCs. Analysis of the growth kinetics, cell cycle and colony-forming ability of
      the isolated human UC-ECFCs indicated that the cells demonstrated properties of
      stem cells, including relative stability and rapid proliferation in vitro. Gene
      expression of Fms related tyrosine kinase 1, kinase insert domain receptor,
      vascular endothelial cadherin, cluster of differentiation (CD)31, CD34, epidermal
      growth factor homology domains-2, von Willebrand factor and endothelial nitric
      oxide synthase was assessed by reverse transcription-polymerase chain reaction.
      The cells were positive for CD34, CD31, CD73, CD105 and vascular endothelial
      growth factor receptor-2, and negative for CD45, CD90 and human leukocyte antigen
      antigen D related protein according to flow cytometry. 1,1'-dioctadecyl-3,3,3',3'
      tetra-methyl-indocarbocyanine perchlorate-labeled acetylated low-density
      lipoprotein and fluorescein isothiocyanate-Ulex europaeus-l were used to verify
      the identity of the UC-ECFCs. Matrigel was used to investigate tube formation
      capability. The results demonstrated that the reported technique is a valuable
      method for isolating human UC-ECFCs, which have potential for use in vascular
      regeneration.

PMID- 29067105
TI  - Molecular epidemiology study of measles viruses in Kunming area of China.
AB  - The present study assessed the variation of measles viruses (MV) and its
      association with clinical manifestations in patients with MV. A total of 38
      pediatric patients with MV at the acute infection stage were selected and 2 ml
      venous blood was collected from each of them. Serum immunoglobulin M antibodies
      were determined by ELISA. Urine specimens were collected from 30 of the 38
      patients and associated genetic structures were detected by reverse-transcription
      polymerase chain reaction mapping. At the same time, clinical epidemiological
      manifestations were collected to perform an epidemiological analysis. The MV
      positive rate within the cohort determined in serum was 100%. Seven MV strains
      were isolated from urine specimens of 30 patients and the positive rate was
      23.33%. Four MV strains were randomly selected from the 7 strains and the results
      revealed that they were all of the H1a genotype. In addition, there was no
      significant correlation between clinical manifestation of pediatric patients with
      measles and the genotype of the MV. In conclusion, the preponderant genotype of
      MV in Kunming was H1a and there was obvious nucleotide or amino acid mutation.
      The clinical manifestation of MV infection in pediatric patients was not
      associated with the MV genotype.

PMID- 29067106
TI  - Role of blocking ADAM10 hydrolysis site on N-cadherin by single-chain antibody in
      ventricular remodeling.
AB  - The present study aimed to investigate the roles of the hydrolytic process of N
      cadherin by A disintegrin and metalloproteases 10 (ADAM10) in sustaining
      myocardial structure and integrity, and discuss the mechanisms of ventricular
      remodeling in dilated cardiomyopathy (DCM). Single chain variable fragment
      antibody (ScFv) with the ability to specifically block the ADAM10 hydrolysis site
      of N-cadherin was designed and constructed. Western blot analysis and flow
      cytometry were used to detect the expression of N-cadherin and its C-terminal
      fragment 1 (CTF1) on cardiomyocytes, and cells were also subjected to a cell
      adhesion assay. Furthermore, in a rat model of dilated cardiomyopathy (DCM), the
      effects of intracardiac injection of the recombinant adenovirus on cardiac
      structure and contractile function were observed by hematoxylin and eosin
      staining and color Doppler echocardiography. The recombinant ScFv-expressing
      adenoviral plasmid with the ability to block the ADAM10 hydrolysis site on N
      cadherin was successfully constructed and efficiently transfected into H9C2
      cells. After transfection, N-cadherin protein expression was significantly
      increased, CTF1 protein was significantly decreased and the adhesion capability
      of myocardial cells was significantly improved. In the in vivo experiment, N
      cadherin expression was significantly increased in the treatment group compared
      with that in the model group, and the structure and function of the heart were
      significantly improved. In conclusion, blocking of the ADAM10 hydrolysis site on
      N-cadherin by ScFv increased N-cadherin expression and improved ventricular
      remodeling. The present study provided experimental evidence for a novel approach
      for the treatment and prevention of DCM.

PMID- 29067108
TI  - Effects of FHL1 and P21 on hypoxia-induced pulmonary vascular remodeling in
      neonatal rats.
AB  - Numerous studies have demonstrated that altered expression levels of four and a
      half LIM domains 1 (FHL1) and P21 are necessary for hypoxia-induced pulmonary
      vascular remodeling in both adult rats and human patients with idiopathic
      pulmonary arterial hypertension. However, whether FHL1 and P21 are present in the
      pulmonary artery and whether these proteins affect pulmonary vascular remodeling
      in hypoxia-induced pulmonary hypertension (HPH) in neonatal rats remain unknown.
      The present study investigated the effects of altered FHL1 and P21 expression on
      pulmonary vascular remodeling in neonatal rats with HPH. A total of 32 newborn
      Sprague-Dawley rats were exposed to hypoxia or room air for 7 or 14 days
      (n=8/subgroup). Parameters including the percentage of medial wall thickness
      (WT%), the percentage of medial wall area (WA%), right ventricular (RV) mean
      pressure, RV hypertrophy index (RVHI) and RV systolic pressure (RVSP) were
      measured to evaluate the development of HPH. Additionally, the expressions of
      FHL1 and P21 in the pulmonary artery smooth muscle cells (PASMCs) were measured
      by reverse transcription-quantitative polymerase chain reaction, western blot
      analysis and immunohistochemical staining. WA%, WT%, RV mean pressure, RVHI and
      RVSP were significantly increased in the HPH model group when compared with the
      control group (P<0.01). The protein expression levels of FHL1 were significantly
      increased in the HPH group (P<0.05), while the mRNA and protein expression levels
      of P21 were significantly reduced (P<0.05). Pearson correlation analysis
      indicated that the protein expressions of FHL1 and P21 were correlated with WA%
      and WT% (all P<0.001), and that the protein expression of P21 was negatively
      correlated with that of FHL1 (P<0.01). The results indicated that the expressions
      of FHL1 and P21 were altered in the PASMCs of newborn rats with HPH. Furthermore,
      FHL1 and P21 may serve important roles in pulmonary vascular remodeling.

PMID- 29067107
TI  - Conventional vs. pulsed-light accelerated corneal collagen cross-linking for the
      treatment of progressive keratoconus: 12-month results from a prospective study.
AB  - The aim of the present study was to compare the clinical outcomes of conventional
      corneal collagen cross-linking (CXL) and pulsed-light accelerated CXL (pl-ACXL)
      in the eyes of patients with progressive keratoconus. A total of 72 eyes with
      progressive keratoconus in 58 patients were equally divided into the CXL and pl
      ACXL treatment groups. The CXL treatment was performed using the UVX 1000 system
      with 0.1% riboflavin solution in 20% dextran presoak for 30 min, and 3 mW/cm2
      ultraviolet A (UVA) light for 30 min. The pl-ACXL group was treated with the KXL
      system using 0.1% riboflavin with HPMC presoak for 10 min, followed by 8 min (1
      sec on/1 sec off) of 30 mW/cm2 UVA light. Patients were evaluated according to
      the uncorrected distance visual acuity (UDVA), corrected DVA (CDVA), refraction,
      maximum keratometry (Kmax), endothelial cell density (ECD), anterior segment
      optical coherence tomography and in vivo confocal microscopy. The follow-up
      period was 12 months. Transient haze was observed in 17 eyes (47.22%) in the CXL
      group and 8 eyes (22.22%) in the pl-ACXL group at 1 month postoperatively. There
      were no significant postoperative differences in the astigmatism, manifest
      refraction spherical equivalent, ECD or thinnest corneal thickness. By contrast,
      UDVA, CDVA and Kmax presented significant improvement at 12 months
      postoperatively in the two groups. The demarcation line depth was 284.94+/-33.29
      um in the CXL group, which was significantly deeper in comparison with that in
      the pl-ACXL group (201.64+/-27.72 um; P<0.01) at 1 month postoperatively. In vivo
      confocal microscopy revealed keratocyte apoptosis and stromal edema at 1 month
      postoperatively, which gradually recovered towards the normal status after 12
      months in the two groups. There were no apparent changes in the posterior stroma
      and endothelium in either group. The results of the present study revealed that
      CXL and pl-ACXL were safe and effective procedures in stabilizing the progression
      of keratoconus. The CXL technique offers more effective visual and topographic
      outcomes compared with pl-ACXL, while pl-ACXL ensures shorter treatment time and
      reduced microstructural damage.

PMID- 29067109
TI  - TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis.
AB  - The differentiation of fibroblasts to myofibroblasts is critical for the
      development of idiopathic pulmonary fibrosis (IPF). T-cell lymphoma invasion and
      metastasis 1 (TIAM1) is known to be associated with amyotrophic lateral sclerosis
      1 and colorectal cancer; however, its role in IPF is unclear. The aim of the
      present study was to investigate the expression and roles of TIAM1 in lung
      fibroblasts during pulmonary fibrosis. It was demonstrated that TIAM1 expression
      was significantly increased in fibrotic lung tissue and lung fibroblasts from
      bleomycin (BLM)-treated mice compared with control mice (P<0.05). TIAM1
      expression and differentiation were significantly upregulated in human lung
      fibroblasts challenged with transforming growth factor-beta (TGF-beta) compared
      with unchallenged cells (P<0.05). Furthermore, inhibition of the nuclear factor
      (NF)-kappaB signaling pathway significantly attenuated TGF-beta-induced TIAM1
      expression and decreased fibroblast differentiation in human lung fibroblasts
      (P<0.05). Similarly, overexpression of TIAM1 significantly inhibited TGF-beta
      induced fibroblast differentiation, as indicated by decreased expression of
      fibronectin and alpha-smooth muscle actin (SMA; P<0.05). The results of the
      present study also demonstrated that TIAM1 knockdown increased TGF-beta-induced
      fibroblast differentiation (P<0.05). These findings suggest that TIAM1 expression
      is associated with lung fibroblast differentiation in pulmonary fibrosis via an
      NF-kappaB-dependent pathway, and that TIAM1 inhibits lung fibroblast
      differentiation in pulmonary fibrosis.

PMID- 29067110
TI  - Growth inhibitory effect of the Src inhibitor dasatinib in combination with
      anticancer agents on uterine cervical adenocarcinoma cells.
AB  - Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with
      squamous cell carcinoma. Therefore, the development of new treatment strategies
      for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is
      important in cancer progression. Dasatinib is a Src inhibitor that has been
      reported to be effective when used in combination with anticancer drugs. The
      present study aimed to confirm Src expression in human cervical adenocarcinoma
      cell lines and to determine the mechanism underlying the inhibitory effect of
      dasatinib on Src signaling in vitro. Western blot analysis was performed to
      investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2
      cells). The cells were cultured for 48 h with the addition of different
      concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count
      was measured using a colorimetric (WST-1) assay. The concentrations of anticancer
      agents were fixed according to the results obtained, and the same experiments
      were performed using the drugs in combination with dasatinib at various
      concentrations to determine the concentrations that significantly affected the
      number of viable cells. The presence or absence of apoptosis was investigated
      using a caspase-3/7 assay. Signal transduction in each cell line was examined
      using western blotting. Src was activated in the two cell lines, and cell
      proliferation was significantly suppressed by each anticancer drug in combination
      with 10 uM dasatinib. Caspase-3/7 activity was also increased and Src signaling
      was suppressed by each anticancer drug in combination with dasatinib. In
      conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and
      dasatinib inhibits intracellular Src signaling and causes apoptosis. The results
      of the present study suggest that Src may be targeted in novel therapeutic
      strategies for cervical adenocarcinoma.

PMID- 29067111
TI  - Evaluation of in vitro and in vivo therapeutic antitumor efficacy of transduction
      of polo-like kinase 1 and heat shock transcription factor 1 small interfering
      RNA.
AB  - Mitotic progression is regulated by the phosphorylation of heat shock
      transcription factor 1 (HSF1) by polo-like kinase 1 (PLK1); however, this
      interaction is often deregulated in tumors. High expression levels of PLK1 and
      HSF1 have been observed in various types of human cancer. In the present study,
      it was investigated whether small interfering (si)RNA against PLK1 or HSF1 could
      suppress tumor growth in vitro and in vivo. In vitro transfection of PLK1 and
      HSF1 siRNA into PKL1- and HSF1-positive human breast tumor MDA-MB-231 and human
      cervical carcinoma HeLa cells inhibited cell growth via suppression of PLK1 and
      HSF1 mRNA expression, respectively. However, the transfection of PLK1 or HSF1
      siRNA did not significantly affect the cytotoxicity of doxorubicin in HeLa cells.
      Furthermore, injection of PKL1 or HSF1 siRNA into mice with liver HeLa metastasis
      suppressed tumor growth. From these findings, PLK1 and HSF1 may be considered to
      be promising targets for antitumor therapy.

PMID- 29067112
TI  - Bone marrow mesenchymal stem cells repair the hippocampal neurons and increase
      the expression of IGF-1 after cardiac arrest in rats.
AB  - The present study aimed to investigate the beneficial effects and underlying
      mechanisms of bone marrow mesenchymal stem cells (BMSCs) on global ischemic
      hypoxic brain injury. Cells collected from the femurs and tibias of male Sprague
      Dawley rats were used to generate BMSCs following three culture passages. A rate
      model of cardiac arrest (CA) was induced by asphyxia. One hour following return
      of spontaneous circulation (ROSC), BMSCs were transplanted through injection into
      the tail vein. Neurological status was assessed using modified neurological
      severity score (mNSS) tests 1, 3 and 7 days following ROSC. Reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining
      were used to detect insulin-like growth factor 1 (IGF-1) expression in the
      hippocampus. Furthermore, double-fluorescent labeling of green fluorescent
      protein (GFP) and IGF-1 was used to detect the IGF-1 expression in transplanted
      BMSCs. Serum levels of protein S100-B were examined using ELISA. GFP-labeled
      BMSCs were observed in the hippocampus at 1, 3 and 7 days post transplantation
      through fluorescent microscopy. BMSC transplantation resulted in reduced protein
      S100-B levels. The mNSS of the BMSC-treatment group was significantly reduced
      compared with that of the CA group. The RT-qPCR analysis and immunohistochemistry
      results demonstrated that BMSC treatment significantly increased IGF-1 expression
      in the hippocampus. In addition, the double-fluorescent labeling results
      demonstrated that transplanted BMSCs expressed IGF-1 in the hippocampus. The
      results of the present study suggest that BMSC treatment promotes the recovery of
      cerebral function following CA in rats possibly through the secretion of IGF-1.

PMID- 29067113
TI  - Photodynamic therapy for biliary tract organ via a novel ultra-small composite
      optical fiberscope.
AB  - Photodynamic therapy (PDT) is a method used treat tumors via utilizing
      photodynamic reactions between photosensitive substances with tumor affinity and
      lasers. For overall bile duct cancers, PDT has been demonstrated to resolve
      stenosis and improve prognosis; however, when limited to intrahepatic bile duct
      cancers, modifications to the laser irradiation are necessary as surrounding
      hepatocytes incorporate a large amount of photosensitive substances. Furthermore,
      the intrahepatic bile duct is thin, and a guide sheath and thin fiber are
      necessary to transport laser irradiation probes to the target region. In the
      present study, a parallel-type ultra-small composite optical fiberscope (COF)
      with an outer diameter of 1 mm or smaller was developed to target a thin
      intrahepatic bile duct. PDT was performed using an animal model and talaporfin
      sodium (Laserphyrin), which is rapidly excreted by hepatocytes and is suitable
      for use with a long-wavelength laser due to its high tissue penetrating ability.
      The results demonstrated that Laserphyrin does not cause necrotic changes in the
      normal biliary tract mucosa. In addition, COF images of sufficient quality were
      acquired. The present results suggest that COF may be used for the treatment of
      deep bile duct lesions.

PMID- 29067114
TI  - Expression and significance of caveolin-1 in hepatitis B virus-associated
      hepatocellular carcinoma.
AB  - Caveolin-1 (Cav-1) is a major component of caveolae and has been recently
      identified as a tumor suppressor. As little is known about Cav-1 in hepatitis B
      virus (HBV)-associated hepatocellular carcinoma (HCC), the aim of the present
      study was to investigate the expression and significance of Cav-1 in HBV
      associated HCC. Semi-quantitative reverse transcription-polymerase chain reaction
      (RT-PCR) was performed to detect the mRNA expression level of Cav-1 in 40 cases
      of HBV-associated HCC, the corresponding 11 non-tumor cases of HBV-associated
      chronic hepatitis, 29 non-tumor cases of HBV-associated cirrhosis and 6 cases of
      normal liver tissues. Immunohistochemical analysis indicated the expression of
      Cav-1, cluster of differentiation 34 and vascular endothelial growth factor
      (VEGF) in HBV-associated HCC tissue samples. In addition, the association of Cav
      1 expression with angiogenesis and clinicopathological characteristics of HBV
      associated HCC was also analyzed. RT-PCR results demonstrated that the expression
      rate of Cav-1 mRNA in HBV-associated HCC, non-tumor HBV-associated chronic
      hepatitis and cirrhosis liver tissues and control normal liver tissues from
      patients with metastatic carcinoma was 92.5, 85.0 and 16.7%, respectively. mRNA
      expression level of Cav-1 was significantly increased in chronic hepatitis,
      cirrhosis and HBV-associated HCC livers compared with normal control livers
      (P<0.05 and P<0.01, respectively). Cav-1 protein was detected by
      immunohistochemistry in 80% of the samples of HBV-associated HCC. Furthermore,
      Cav-1 and VEGF protein expression levels were correlated with microvessel density
      (MVD; gammas<0.46, P=0.01 and gammas<0.31, P=0.05, respectively). In addition,
      Cav-1 expression and MVD were significantly associated with metastasis (P=0.031
      and P=0.046, respectively). In conclusion, Cav-1 may have an important role in
      the carcinogenesis and progression of HBV-associated HCC and angiogenesis may be
      affected by Cav-1 during this process.

PMID- 29067115
TI  - Advanced glycation end products and lipopolysaccharides stimulate interleukin-6
      secretion via the RAGE/TLR4-NF-kappaB-ROS pathways and resveratrol attenuates
      these inflammatory responses in mouse macrophages.
AB  - Macrophages are essential for regulating the physiology of pregnancy; however,
      excessive inflammatory responses to macrophages, induced by infection and/or
      endogenous danger signals, may potentially result in complications during
      pregnancy. Advanced glycation end-products (AGE) and lipopolysaccharides (LPS)
      are known to induce inflammation and are associated with adverse developmental
      outcomes. The aim of the present study was to examine the effect of AGE and LPS
      on cytokines in the J774 murine macrophage cell line and the potential effect of
      resveratrol on AGE- and LPS-induced inflammation in macrophages. AGE and LPS
      significantly increased IL-6 mRNA expression and secretion in J774 macrophages
      (P<0.05). Although AGE and LPS significantly stimulated IL-1beta mRNA expression
      (P<0.05), they had no significant effect on IL-1beta secretion. To assess the
      receptors for AGE and LPS, including receptor for AGE (RAGE) and Toll-like
      receptor (TLR4), blocking reagents (RAGE antagonist or TLR4 inhibitor) were added
      to the J774 macrophages. IL-6 secretion induced by AGE or LPS was significantly
      inhibited by pretreatment with RAGE antagonist (P<0.05) or TLR4 inhibitor
      (P<0.05). IL-6 secretion was dependent on nuclear factor (NF)-kappaB activation
      and the production of reactive oxygen species (ROS; P<0.05). Resveratrol
      suppressed mRNA expression and intracellular IL-6 production, resulting in
      significantly decreased IL-6 secretion after treatment with LPS or AGE (P<0.01).
      Furthermore, treatment with Ex527, which is a sirtuin-1 (SIRT1) inhibitor,
      significantly attenuated the anti-inflammatory effect of resveratrol (P<0.05),
      and treatment with 5-aminoimidazole-4-carboxamide ribonucleotide, which is a 5'
      adenosine monophosphate-activated protein kinase (AMPK) activator, resulted in a
      significant decrease in IL-6 secretion in J774 macrophages (P<0.05). The results
      of the present study indicated that AGE and LPS increase IL-6 secretion depending
      on NF-kappaB activation and ROS production through RAGE and/or TLR4 in the J774
      murine macrophage cell line. Based on the present study, resveratrol appears to
      be an effective regulator of the inflammatory responses associated with SIRT1 and
      AMPK activation in macrophages. These results suggest that resveratrol may have
      therapeutic applications for controlling immune responses during pregnancy.

PMID- 29067116
TI  - Effect of isoflurane + N2O inhalation and propofol + fentanyl anesthesia on
      myocardial function as assessed by cardiac troponin, caspase-3, cyclooxygenase-2
      and inducible nitric oxide synthase expression.
AB  - The aim of this study was to evaluate the effect of isoflurane + N2O inhalation
      and propofol + fentanyl anesthesia on myocardial function as assessed by cardiac
      troponin T (cTnT). A total of 60 patients were randomized into two groups:
      isoflurane + N2O inhalation (n=30) and propofol + fentanyl anesthesia (n=30). The
      findings demonstrated that there was no significant difference between the two
      experimental groups in terms of cTnT levels, demographic properties or
      hemodynamic parameters. Isoflurane + N2O inhalation and propofol + fentanyl
      anesthesia, respectively, were also investigated in a rat model of myocardial
      infarction. Myocardial cell damage, inflammation and oxidative stress levels,
      caspase-3/9 activities and cyclooxygenase-2 protein expression were markedly
      decreased, although there was no statistical significance difference between the
      two experimental groups. Notably, inducible nitric oxide synthase protein
      expression in the isoflurane + N2O inhalation group was significantly higher than
      that of the propofol + fentanyl anesthesia group (P<0.01). In conclusion,
      isoflurane + N2O inhalation and propofol + fentanyl anesthesia are not associated
      with risks for myocardial function.

PMID- 29067117
TI  - Spontaneously hypertensive rats are sensitive to thoracic aorta damage induced by
      a hot and humid environment.
AB  - The purpose of this study was to investigate the effect of a hot and humid
      environment on thoracic aorta damage in spontaneously hypertensive rats (SHRs).
      Wistar-Kyoto (WKY) rats were randomly divided into three groups (n=8 in each
      group): Control group (WKY-CN), heat exposure for 8 h group (WKY-8) and heat
      exposure for 24 h group (WKY-24). The CN group was exposed to room temperature
      (24 degrees C); WKY-8 and WKY-24 group were exposed to heat (32 degrees C) and
      65% relative humidity for 8 and 24 h, respectively. Accordingly, SHRs were
      randomly divided into three groups (n=8 each group): SHR-CN, SHR-8 and SHR-24.
      After 7 days of heat exposure, the weight, food consumption and blood pressure of
      rats was measured. Noradrenaline (NA)-induced contraction of aorta rings was
      measured using an organ bath system, and vascular morphology was observed.
      Expression levels of apoptotic genes and proteins in the thoracic aorta were also
      measured. The experimental results indicated that, in the heat exposure
      environment, rat food intake was reduced. Rat weight was significantly increased
      in all groups except SHR-24 (all P<0.01 except SHR-8, P<0.05). Heat exposure
      significantly increased the blood pressure of rats in the WKY-24 (P<0.01 for
      systolic; P<0.05 for diastolic), SHR-8 and SHR-24 (all P<0.01) groups. This
      effect was more notable in SHR compared with WKY. NA-induced contraction of aorta
      rings significantly increased in the SHR-CN group, compared with the WKY-CN group
      (P<0.01). Heat exposure significantly elevated the NA-induced contraction in both
      8 h groups compared with the CN groups (P<0.01). This effect was accompanied by
      structural damage to the thoracic aorta and increased expression of apoptotic
      genes and proteins. In conclusion, thoracic aorta damages in SHRs were more
      sensitive to heat exposure. The enhanced NA-induced contraction may have partly
      been due to increased apoptosis in the thoracic aorta.

PMID- 29067118
TI  - Tectorigenin attenuates the MPP+-induced SH-SY5Y cell damage, indicating a
      potential beneficial role in Parkinson's disease by oxidative stress inhibition.
AB  - Tectorigenin is a plant isoflavonoid primarily derived from the flowers of
      Pueraria thomsonii Benth. Although various biological properties of tectorigenin
      have been reported, such as its antioxidant activity, the effects of tectorigenin
      on the cellular models of Parkinson's disease have not yet been elucidated. The
      aims of the current study were to investigate whether tectorigenin prevents
      neurotoxicity induced by MPP+ (also known as 1-methyl-4-phenylpyridinium) in SH
      SY5Y cells and to elucidate the underlying protective mechanism. Cell viability
      and lactate dehydrogenase release were measured. The morphological changes of
      apoptotic cells were observed by Hoechst 33258 staining. Caspase-3, superoxide
      dismutase, catalase and glutathione peroxidase activity was measured using
      commercially available ELISA kits. The expression of cytochrome c, Bax, Bcl-2 and
      NADPH oxidase were detected by western blot analysis. The results indicated that
      treatment with MPP+ causes a significant decrease in the viability of cells and
      an increase in apoptosis, as evidenced by the upregulation of apoptotic cells,
      caspase-3 activity and cytochrome c expression. By contrast, these effects were
      all reversed by pretreatment with tectorigenin in SH-SY5Y cells. Tectorigenin
      also inhibited the MPP+-induced changes of Bax and Bcl-2 levels. In addition,
      pretreatment with tectorigenin mitigated the MPP+-caused increases in the levels
      of reactive oxygen species and NADPH oxidase protein in SH-SY5Y cells.
      Simultaneously, tectorigenin abolished the downregulation of antioxidant enzymes,
      including superoxide dismutase, catalase and glutathione peroxidase, that was
      induced by MPP+. In conclusion, the present study data indicate that the
      neuroprotective effect of tectorigenin against MPP+-induced cytotoxicity and
      apoptosis may be involved in attenuating oxidative stress and enhancing
      antioxidant defense.

PMID- 29067119
TI  - MiR-148a modulates HLA-G expression and influences tumor apoptosis in esophageal
      squamous cell carcinoma.
AB  - Esophageal cancer (EC) is a common malignant tumor type, and esophageal squamous
      cell carcinoma (ESCC) accounts for the majority of EC cases. Previous studies
      have reported that microRNA (miR)-148a is downregulated in patients with
      recurrent EC. The human leukocyte antigen-G (HLA-G) is expressed to a high level
      in primary ESCC tissues and is associated with prognosis. A previous luciferase
      assay indicated that HLA-G is a target of miR-148a regulation. The aim of the
      current study was to investigate the expression level of miR-148a in primary
      ESCC. The regulatory role of miR-148a in HLA-G expression and cell proliferation
      in ESCC cells was also investigated. The relative expression level of miR-148a
      was compared between ESCC tumor tissues and adjacent normal tissues. The human
      ESCC cell line EC9706 was transfected with miR-148a mimic, non-homologous RNA
      duplex (negative control; NC) or empty vector (blank control; BC). Reverse
      transcription-quantitative polymerase chain reaction and western blot analysis
      were used to assess the level of HLA-G expression. The cells were stained with
      Annexin V-fluorescein isothiocyanate/propidium iodide and cell apoptosis was
      evaluated by flow cytometry. The level of miR-148a expression was significantly
      lower in primary ESCC tissues compared with adjacent normal tissues (P<0.01). In
      EC9706 cells transfected with miR-148a mimic, the rate of apoptosis was increased
      ~13-fold when compared with BC cells (P<0.01). Furthermore, the mRNA level of HLA
      G was significantly reduced in cells transfected with miR-148a mimic (P<0.01).
      The protein levels of HLA-G were also notably decreased. Transfection with non
      homologous RNA duplex did not influence the rate of cell apoptosis or expression
      of HLA-G when compared with the BC group. In conclusion, miR-148a was indicated
      to be involved in carcinogenesis in primary ESCC through the regulation of HLA-G
      expression. The current results suggest that miR-148a is a potential biomarker of
      ESCC.

PMID- 29067120
TI  - Simvastatin attenuates renal ischemia/reperfusion injury from oxidative stress
      via targeting Nrf2/HO-1 pathway.
AB  - Ischemia-reperfusion (I/R) injury of the kidneys is commonly encountered in the
      clinic. The present study assessed the efficacy of simvastatin in preventing I/R
      induced renal injury in a rat model and investigated the corresponding molecular
      mechanisms. Rats were divided into 3 groups, including a sham, I/R and I/R +
      simvastatin group. The results revealed that in the I/R group, the levels of
      blood urea nitrogen, serum creatinine and lactate dehydrogenase were
      significantly higher than those in the sham group, which was significantly
      inhibited by simvastatin pre-treatment. I/R significantly decreased superoxide
      dismutase activity compared with that in the sham group, which was largely
      rescued by simvastatin. Furthermore, I/R significantly increased the
      malondialdehyde content compared with that in the sham group, which was reduced
      by simvastatin. Hematoxylin-eosin staining revealed no obvious morphological
      abnormalities in the sham group, while I/R led to notable tubular cell swelling,
      vacuolization, cast formation and tubular necrosis, which was rescued by
      simvastatin. A terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end labeling assay demonstrated that I/R significantly
      increased the number of apoptotic cells compared with that in the sham group,
      which was significantly inhibited by simvastatin. Western blot analysis
      demonstrated that simvastatin upregulated I/R-induced increases of nuclear factor
      erythroid-2-related factor 2 (Nrf2) and anti-oxidant enzyme heme oxygenase-1 (HO
      1). Reverse-transcription quantitative PCR indicated that changes in the mRNA
      levels of Nrf2 and HO-1 were consistent with the western blot results. It was
      concluded that simvastatin treatment led to upregulation of HO-1 protein levels
      through activating the Nrf2 signaling pathway to ultimately protect the kidneys
      from I/R-associated oxidative damage.

PMID- 29067121
TI  - Effect of testosterone and hypoxia on the expansion of umbilical cord blood CD34+
      cells in vitro.
AB  - Successfully expanding hematopoietic stem cells (HSCs) is advantageous for
      clinical HSC transplantation. The present study investigated the influence of
      testosterone on the proliferation, antigen phenotype and expression of
      hematopoiesis-related genes in umbilical cord blood-derived cluster of
      differentiation (CD)34+ cells under normoxic or hypoxia conditions. Cord blood
      (CB) CD34+ cells were separated using magnetic activated cell sorting. A cytokine
      cocktail and feeder cells were used to stimulate the expansion of CD34+ cells
      under normoxic (20% O2) and hypoxic (1% O2) conditions for 7 days and
      testosterone was added accordingly. Cells were identified using flow cytometry
      and reconstruction capacity was determined using a colony-forming unit (CFU)
      assay. The effects of oxygen concentration and testosterone on the expression of
      hematopoietic-related genes, including homeobox (HOX)A9, HOXB2, HOXB4, HOXC4 and
      BMI-1, were measured using reverse transcription-quantitative polymerase chain
      reaction. The results indicated that the number of CFUs and total cells in the
      testosterone group increased under normoxic and hypoxic conditions compared with
      the corresponding control groups. Furthermore, the presence of testosterone
      increased the number of CFU-erythroid colonies. In liquid culture, the growth of
      CD34+ cells was rapid under normoxic conditions compared with under hypoxic
      conditions, however CD34+ cells were maintained in an undifferentiated state
      under hypoxic conditions. The addition of testosterone under hypoxia promoted the
      differentiation of CD34+ cells into CD34+CD38+CD71+ erythroid progenitor cells.
      Furthermore, it was determined that the expression of hematopoietic-related genes
      was significantly increased (P<0.05) in the hypoxia testosterone group compared
      with the other groups. Therefore, the results of the current study indicate that
      a combination of hypoxia and testosterone may be a promising cultivation
      condition for HSC/hemopoietic progenitor cell expansion ex vivo.

PMID- 29067122
TI  - Analgesic activity of cynaropicrinon on post-inflammatory irritable bowel
      syndrome visceral hypersensitivity in a rat model.
AB  - Visceral hypersensitivity is one of the most common symptoms in patients with
      post-inflammatory-irritable bowel syndrome (PI-IBS). Enterochromaffin (EC) cells
      and 5-hydroxytryptamine (5-HT) are important in the development of visceral
      hyperalgesia, and EC cells are influenced by helper T-cell subtype 1 or 2
      cytokine predominant environments. In the present study, the analgesic effect of
      cynaropicrin and its underlying mechanism on the treatment of trinitrobenzene
      sulfonic (TNBS)-induced PI-IBS visceral hyperalgesia rats was investigated. The
      results from the abdominal withdrawal reflex tests and electromyography
      recordings indicated that treatment with cynaropicrin significantly and dose
      dependently alleviated the visceral hyperalgesia of PI-IBS rats (P<0.05). In
      addition, the increased colonic 5-HT content, colonic tryptophan hydroxylase
      expression, EC cell number and the cytokine levels, including tumor necrosis
      factor-alpha and interleukin-6 in PI-IBS rats were significantly alleviated by
      cynaropicrin (P<0.05). These data demonstrate that the analgesic activity of
      cynaropicrin on TNBS-induced PI-IBS visceral hypersensitive rats was mediated via
      reduction of cytokines levels. Thus, cynaropicrin as a bioactive natural product
      may offer promising therapeutic avenues for visceral hypersensitivity in IBS.

PMID- 29067123
TI  - Alcoholization of pyogenichepatic abscess with absolute alcohol in Bama minipigs.
AB  - Pyogenic hepatic abscess (PHA) is a rare, but potentially serious disease. At
      present, ultrasound-guided or computed tomography-guided percutaneous needle
      aspiration or catheter drainage is appropriate as a first-line treatment.
      However, it is difficult to aspirate or drain pus and to select the appropriate
      antibiotic therapy if the abscess consists of thick pus and polymicrobial
      confections, or its pathogenic bacterium is multidrug resistant and cryptogenic.
      Case studies of alcoholization provide a novel method to manage PHA. However, the
      efficacy and safety of this treatment should be further evaluated. In the present
      study, the therapeutic efficacy and complications of alcoholization for PHAs in
      Bama minipigs were investigated. PHAs were prospectively treated by ultrasound
      guided percutaneous instillation of absolute alcohol in the abscess cavity. The
      criteria for considering a successful intervention were met in all minipigs
      subsequent to alcoholization twice within 14 days. The procedures were well
      tolerated in all animals, and there were no alcoholic adverse effects or
      procedure-associated complications. In conclusion, ultrasound-guided percutaneous
      alcoholization is a safe and effective procedure to manage PHA. The problems of
      thick pus aspiration and selection of an appropriate antibiotic observed in other
      treatments were resolved effectively using alcoholization. This technique may
      reduce the treatment period and possibly become a novel strategy for the
      management of PHA.

PMID- 29067124
TI  - MicroRNA-21 regulates the viability and apoptosis of diffuse large B-cell
      lymphoma cells by upregulating B cell lymphoma-2.
AB  - Diffuse large B-cell lymphoma (DLBCL), one of the most frequently diagnosed non
      Hodgkin lymphoma (NHL), is partly attributed to hereditary factors. MicroRNA-21
      (miR-21) is an oncogenic substance that induces NHL and primarily targets tumor
      suppressive molecules, such as B cell lymphoma-2 (Bcl-2). The present study
      explored whether Bcl-2, targeted by miR-21, would affect the development of NHL.
      Specimens were harvested from 55 patients with DLBCL who had undergone surgical
      treatment. Expression levels of miR-21 and Bcl-2 were evaluated through reverse
      transcription-quantitative polymerase chain reaction, immunohistochemistry and
      western blotting. Luciferase-reporter assays were performed to investigate the
      potential association between miR-21 and Bcl-2. MTT assays, flow cytometric
      analysis and caspase-3 activity assays were used to evaluate cell viability and
      apoptosis of DLBCL cells, respectively. Furthermore, statistical analysis was
      conducted using SPSS 19.0 software and the expression levels of miR-21 and Bcl-2
      within DLBCL tissues were significantly upregulated when compared to those in
      normal tissues (P<0.01). As predicted by TargetScan, perfect base pairing was
      observed between the seed sequence of mature miR-21 and the 3' untranslated
      region of Bcl-2 mRNA. Dual luciferase reporter gene assays also revealed that miR
      21 significantly facilitated the luciferase activity of Bcl-2 wild-type, with 61%
      upregulation (P<0.01) observed. MTT assays demonstrated that the viability of OCI
      LY3 cells was decreased when cells were transfected with miR-21 inhibitor or Bcl
      2 small interfering RNA and compared with those of control and negative control
      groups (all P<0.05). The apoptosis rate and caspase-3 activity level of the miR
      21 group were 2.73+/-0.48 and 0.47+/-0.05, respectively, which were both
      significantly different from the groups with lower levels of miR-21 expression
      levels (all P<0.01). Since miR-21 may contribute to increased viability and
      decreased apoptosis of DLBCL cells through targeting Bcl-2, both Bcl-2 and miR-21
      are likely to serve as effective targets for developing novel DLBCL treatments in
      the future.

PMID- 29067125
TI  - Long non-coding RNA HOX transcript antisense RNA promotes expression of 14-3
      3sigma in non-small cell lung cancer.
AB  - Evidence suggests that both 14-3-3sigma and long non-coding RNA HOX transcript
      antisense RNA (HOTAIR) are involved in the tumorigenesis and progression of lung
      cancer. In the present study, the potential association between 14-3-3sigma and
      HOTAIR in non-small cell lung cancer (NSCLC) was investigated. In tissue samples
      collected from 54 patients with NSCLC, expression of HOTAIR and 14-3-3sigma was
      analyzed by reverse transcription-quantitative polymerase chain reaction (RT
      qPCR). After stable ectopic expression of HOTAIR and stable HOTAIR knockdown in
      PC9 cancer cells, the effect of HOTAIR on levels of mRNA and protein 14-3-3sigma
      expression levels were detected using RT-qPCR and western blotting, respectively.
      Expression of HOTAIR and 14-3-3sigma in NSCLC tissues was significantly higher
      than in adjacent non-cancerous lung tissue (P<0.05). Correlation analysis also
      identified a correlation between levels of HOTAIR and 14-3-3sigma expression in
      NSCLC tissues (r=0.725, P=0.0005). In addition, overexpression and knockdown of
      HOTAIR in the human NSCLC cell line PC9 led to the upregulation and
      downregulation of 14-3-3sigma, respectively, at both the mRNA and protein levels
      (all P<0.05). To the best of our knowledge, the present study provides the first
      in vivo and in vitro evidence to suggest that HOTAIR promotes the expression of
      14-3-3sigma in NSCLC. The potential association between HOTAIR and 14-3-3sigma
      indicates that both biomolecules may be viable targets in anticancer therapy.

PMID- 29067126
TI  - Early surgery increases mitochondrial DNA release and lung injury in a model of
      elderly hip fracture and chronic obstructive pulmonary disease.
AB  - Hip fractures are one of the most common injuries in elderly individuals and are
      associated with a high incidence of complications and mortality. Clinical
      guidelines recommend early reparative surgery within 24-48 h from hospital
      admission; however, it is currently unknown whether this principle of early
      surgery is applicable for patients with hip fracture and chronic obstructive
      pulmonary disease (COPD). To investigate the systemic inflammatory response and
      lung injury as a result early surgery in elderly patients with hip fracture and
      COPD, a COPD model was created, by daily exposure to cigarette smoke, and
      evaluated. Rats (5 months of age) were exposed to cigarette smoking for 37 weeks
      to create a COPD group. Rats not exposed to cigarette smoke formed the control
      group. All rats experienced hip fracture, which was subsequently treated with
      surgery at 24 h (early fixation; EF) or 72 h (late fixation; LF) after fracture,
      respectively. Serum mitochondrial DNA (mtDNA), tumor necrosis factor-alpha (TNF
      alpha), interleukin (IL)-6 and IL-10 were measured at 2 and 24 h after surgery.
      Cytokine and myeloperoxidase (MPO) activity in the lung tissue were measured and
      assessed via bronchoalveolar lavage. The serum mtDNA, IL-6 and IL-10 levels in
      the control group and in the COPD group increased rapidly at 2 h and peaked at 24
      h, while TNF-alpha levels peaked at 2 h and subsequently decreased. Rats that
      received EF in the COPD group demonstrated a significant increase of TNF-alpha
      (P<0.001 at 2 h), IL-6 (P<0.001 at 2 and 24 h), IL-10 (P=0.010 at 2 h and P=0.001
      at 24 h) and mtDNA (P<0.001 at 24 h) compared with the rats that received LF. LF
      in experimental rats also significantly reduced the severity of MPO activity
      (P<0.001 and P=0.001) and permeability (P=0.009 and P=0.018) in pulmonary samples
      at 2 or 24 h, respectively, compared with EF. However, LF in the control group
      did not demonstrate a significant advantage at reducing MPO and permeability in
      serum and pulmonary samples. The present study indicated that early surgery
      increased mtDNA and cytokine release in a model of elderly hip fracture with
      COPD, and LF may reduce the severity of the inflammatory response and degree of
      permeability in pulmonary tissues.

PMID- 29067127
TI  - Inhibition of miR-27a suppresses the inflammatory response via the p38/MAPK
      pathway in intervertebral disc cells.
AB  - The current study aimed to investigate the role of miR-27a in intervertebral disc
      degeneration (IDD) and to examine the underlying mechanisms. Quantitative
      polymerase chain reaction (qPCR) was performed to detect the expression level of
      miR-27a in the nucleus pulposus (NP) tissues of patients with IDD, and the
      results revealed an increasing expression of miR-27a in IDD compared with the
      control. To further investigate the role of miR-27a in IDD, a stable human NP
      cell line with low miR-27a expression was generated by transfecting cells with a
      lentiviral antigomiR-27a inhibitor. In addition, a human NP cell inflammation
      model was established by lipopolysaccharide (LPS; 10 uM) stimulation. The miR-27a
      expression in NP cells was determined by qPCR, while the expression of its target
      proteins; p-p38 and nuclear factor (NF-kappaB) was measured by western blot
      analysis. Furthermore, the mRNA and protein expression levels of proinflammatory
      factors, including interleukin (IL)-1beta, IL-6 and tumor necrosis factor-alpha
      (TNF-alpha), were also evaluated by qPCR and ELISA, respectively. The current
      results confirmed that miR-27a was significantly upregulated in IDD. In vitro,
      downregulation of miR-27a in LPS-stimulated NP cells by transfection with the miR
      27a inhibitor resulted in suppression of p-p38 and NF-kappaB expression levels.
      Furthermore, the production of the proinflammatory factors IL-1beta, IL-6 and TNF
      alpha was significantly reduced in LPS-stimulated NP cells with downregulated miR
      27a. In conclusion, miR-27a may function as a promoter in IDD development, while
      inhibition of miR-27a may suppress proinflammatory factors released by
      intervertebral disc cells by regulating the p38/mitogen-activated protein kinase
      (MAPK) signaling pathway.

PMID- 29067128
TI  - I-BET151 inhibits expression of RANKL, OPG, MMP3 and MMP9 in ankylosing
      spondylitis in vivo and in vitro.
AB  - Ankylosing spondylitis (AS) is characterized by osteoclastogenesis and
      inflammatory bone resorption. The present study aimed to investigate the effect
      of bromodomain and extra-terminal domain (BET) protein inhibitor I-BET151 on AS
      process. A total of 38 AS Chinese patients were recruited and a further 38 sex-
      and age-matched healthy participants were selected as control. The Bath AS
      Function Index and Bath AS Disease Activity Index were assessed in AS patients
      and levels of erythrocyte sedimentation rate and C-reactive protein were measured
      in AS and healthy groups. Serum from AS patients was used to induce MG63
      osteoblasts and BET inhibitor I-BET151 at concentrations of 50, 100 and 200 ng/ml
      used for treatment of the cells. A HLA-B27/beta2m transgenic AS Lewis rat model
      was established and treated with 30 mg/kg I-BET151 for 5 weeks. Levels of
      receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin
      (OPG), matrix metalloproteinase (MMP)3, and MMP9 were measured using ELISA in
      vivo and additionally detected with western blotting and polymerase chain
      reaction in vitro. The levels of RANKL, OPG, MMP3 and MMP9 were upregulated in AS
      serum, AS serum treated MG63 cells and HLA-B27/beta2m transgenic AS rats.
      Conversely, levels of RANKL, OPG, MMP3 and MMP9 were significantly inhibited in
      cells or animals treated with I-BET151. Overall, the results of the present study
      demonstrated that BET inhibitor I-BET151 suppresses levels of RANKL, OPG, MMP3
      and MMP9 in AS in vivo and in vitro. I-BET151 may exhibit the potential to be
      used as a therapeutic in the treatment of AS patients.

PMID- 29067129
TI  - Dynamical responses to external stimuli for both cases of excitatory and
      inhibitory synchronization in a complex neuronal network.
AB  - For studying how dynamical responses to external stimuli depend on the synaptic
      coupling type, we consider two types of excitatory and inhibitory synchronization
      (i.e., synchronization via synaptic excitation and inhibition) in complex small
      world networks of excitatory regular spiking (RS) pyramidal neurons and
      inhibitory fast spiking (FS) interneurons. For both cases of excitatory and
      inhibitory synchronization, effects of synaptic couplings on dynamical responses
      to external time-periodic stimuli S(t) (applied to a fraction of neurons) are
      investigated by varying the driving amplitude A of S(t). Stimulated neurons are
      phase-locked to external stimuli for both cases of excitatory and inhibitory
      couplings. On the other hand, the stimulation effect on non-stimulated neurons
      depends on the type of synaptic coupling. The external stimulus S(t) makes a
      constructive effect on excitatory non-stimulated RS neurons (i.e., it causes
      external phase lockings in the non-stimulated sub-population), while S(t) makes a
      destructive effect on inhibitory non-stimulated FS interneurons (i.e., it breaks
      up original inhibitory synchronization in the non-stimulated sub-population). As
      results of these different effects of S(t), the type and degree of dynamical
      response (e.g., synchronization enhancement or suppression), characterized by the
      dynamical response factor [Formula: see text] (given by the ratio of
      synchronization degree in the presence and absence of stimulus), are found to
      vary in a distinctly different way, depending on the synaptic-coupling type.
      Furthermore, we also measure the matching degree between the dynamics of the two
      sub-populations of stimulated and non-stimulated neurons in terms of a "cross
      correlation" measure [Formula: see text]. With increasing A, based on [Formula:
      see text], we discuss the cross-correlations between the two sub-populations,
      affecting the dynamical responses to S(t).

PMID- 29067130
TI  - A decision-making model based on a spiking neural circuit and synaptic
      plasticity.
AB  - To adapt to the environment and survive, most animals can control their behaviors
      by making decisions. The process of decision-making and responding according to
      cues in the environment is stable, sustainable, and learnable. Understanding how
      behaviors are regulated by neural circuits and the encoding and decoding
      mechanisms from stimuli to responses are important goals in neuroscience. From
      results observed in Drosophila experiments, the underlying decision-making
      process is discussed, and a neural circuit that implements a two-choice decision
      making model is proposed to explain and reproduce the observations. Compared with
      previous two-choice decision making models, our model uses synaptic plasticity to
      explain changes in decision output given the same environment. Moreover,
      biological meanings of parameters of our decision-making model are discussed. In
      this paper, we explain at the micro-level (i.e., neurons and synapses) how
      observable decision-making behavior at the macro-level is acquired and achieved.

PMID- 29067131
TI  - Right cerebral hemispheric sensitivity to pH and physiological ions in fixed post
      mortem Wistar rat brains.
AB  - Post-mortem human neural tissues fixed in ethanol and aldehyde-based solutions
      express modulated frequency-dependent microvolt potentials when probed by
      chemical and electrical stimuli. These observations run contrary to the
      assumption that basic tissue functions are irreversibly impaired upon fixation,
      in the absence of nutrients and sufficient concentrations of physiological ions.
      The aim of the current study was to investigate the relative effects of pH and
      specific charged particles relevant to normal cell physiology upon electric
      potentials associated with fixed post-mortem rat brain tissue. We identified a
      positive relationship between the total time the brains had been immersed in
      ethanol-formalin-acetic acid and high-frequency microvolt potentials within the
      dorsal right hemisphere of the rat cerebrum. Measuring the pH of the fixative
      solution surrounding the brains indicated that as time increased, a logarithmic
      trend toward alkalinity could be observed. Further experiments revealed that high
      frequency microvolt potentials were related to pH changes within the right
      hemisphere only. The right ventral cerebrum displayed a unique response to
      potassium chloride in ways uncounted for by pH alone. The results suggest that
      the fixed post-mortem right cerebrum of the rat is particularly sensitive to pH
      and physiological ions which explains a subset of previous findings with respect
      to stimulus-response patterns in human coronal brain sections. A concluding
      hypothesis is presented which suggests that brain tissue expresses material
      properties independent of metabolic activity though perhaps relevant to living
      brain function.

PMID- 29067132
TI  - Computational study on neuronal activities arising in the pre-Botzinger complex.
AB  - Experimental investigations have shown that the pre-Botzinger complex (pre-BotC)
      within the mammalian brainstem generates the inspiratory phase of respiratory
      rhythm. Based on a single-compartment model of a pre-BotC inspiratory neuron, we,
      in this paper, use semi-analytical, numerical as well as fast-slow dynamical
      methods to investigate the effects of sodium conductance ([Formula: see text])
      and potassium conductance ([Formula: see text]) on the firing activities of pre
      BotC and try to reveal the dynamical mechanisms behind them. We show how
      [Formula: see text] and [Formula: see text] affect the bifurcations of the fast
      subsystem and how the the firing patterns of pre-BotC transit according to the
      bifurcations.

PMID- 29067133
TI  - Extreme learning machines for regression based on V-matrix method.
AB  - This paper studies the joint effect of V-matrix, a recently proposed framework
      for statistical inferences, and extreme learning machine (ELM) on regression
      problems. First of all, a novel algorithm is proposed to efficiently evaluate the
      V-matrix. Secondly, a novel weighted ELM algorithm called V-ELM is proposed based
      on the explicit kernel mapping of ELM and the V-matrix method. Though V-matrix
      method could capture the geometrical structure of training data, it tends to
      assign a higher weight to instance with smaller input value. In order to avoid
      this bias, a novel method called VI-ELM is proposed by minimizing both the
      regression error and the V-matrix weighted error simultaneously. Finally,
      experiment results on 12 real world benchmark datasets show the effectiveness of
      our proposed methods.

PMID- 29067135
TI  - The braingraph.org database of high resolution structural connectomes and the
      brain graph tools.
AB  - Based on the data of the NIH-funded Human Connectome Project, we have computed
      structural connectomes of 426 human subjects in five different resolutions of 83,
      129, 234, 463 and 1015 nodes and several edge weights. The graphs are given in
      anatomically annotated GraphML format that facilitates better further processing
      and visualization. For 96 subjects, the anatomically classified sub-graphs can
      also be accessed, formed from the vertices corresponding to distinct lobes or
      even smaller regions of interests of the brain. For example, one can easily
      download and study the connectomes, restricted to the frontal lobes or just to
      the left precuneus of 96 subjects using the data. Partially directed connectomes
      of 423 subjects are also available for download. We also present a GitHub
      deposited set of tools, called the Brain Graph Tools, for several processing
      tasks of the connectomes on the site http://braingraph.org.

PMID- 29067136
TI  - Amyotrophic Lateral Sclerosis: An Acupuncture Approach.
AB  - Background: Amyotrophic lateral sclerosis (ALS) is an adult onset
      neurodegenerative disorder that has no curative treatment and is usually fatal.
      Modern medicine treatment is mostly supportive. Acupuncture has much more to
      offer by way of symptomatic relief and improving quality of life (QoL). Useful
      points for the treatment of bulbar paralysis, paralysis of upper and lower
      extremities, and correction of underlying Disharmony Patterns are discussed and
      an illustrative case is presented to demonstrate the acupuncture approach for
      treating ALS. Case: A 55-year-old woman had weakness in her right arm and both
      legs for 4 months. She also had muscle cramps and clumsiness in the affected
      limbs, which rapidly progressed in the 4 months prior to presentation. She was
      diagnosed with ALS, given 50 mg of oral riluzole per day, and told that the
      condition was fatal. She sought acupuncture and was treated for two courses of 8
      weeks each. Results: After acupuncture, this patient's symptomatic relief was
      near perfect in that she became free from disabling symptoms and is now leading a
      normal life. Conclusions: Acupuncture can be an effective modality of treatment
      for ALS, producing symptomatic relief and improving QoL.

PMID- 29067134
TI  - Attention is shaped by semantic level of event-structure during speech
      comprehension: an electroencephalogram study.
AB  - The present electroencephalogram study used an attention probe paradigm to
      investigate how semantic and acoustic structures constrain temporal attention
      during speech comprehension. Spoken sentences were used as stimuli, with each one
      containing a four-character critical phrase, of which the third character was the
      target character. We manipulated not only the semantic relationship between the
      target character and the immediately preceding two characters, but also the
      presence/absence of a pitch accent on the first character. In addition, an
      attention probe was either presented concurrently with the target character or
      not. The results showed that the N1 effect evoked by the attention probe was of
      larger amplitude and started earlier (enhanced attention) when the target
      character and the preceding two characters belonged to the same semantic event
      than when they spanned a semantic-event boundary, and this effect occurred only
      in the un-accented conditions. The results suggest that, during speech
      comprehension, the semantic level of event-structure can constrain attention
      allocation along the temporal dimension, and reverse the attention attenuation
      effect of prediction; meanwhile, the semantic and acoustic levels of event
      structure interact with each other immediately to modulate auditory-temporal
      attention. The results were discussed with regard to the predictive coding
      account of attention.

PMID- 29067138
TI  - Does Ear Acupuncture Have a Role for Pain Relief in the Emergency Setting? A
      Systematic Review and Meta-Analysis.
AB  - Objective: Ear acupuncture might be the form of acupuncture best suited to
      improving acute pain management in the emergency department (ED). The primary aim
      of this review was to assess the analgesic efficacy of ear acupuncture in the ED.
      Secondary outcomes included measures of patient satisfaction, adverse effects,
      cost, administration techniques, and reduction of medication usage. Methods:
      Seven databases and Google Scholar were searched up to April 27, 2017, using MeSH
      descriptors for three overarching themes (ear acupuncture, pain management, and
      emergency medicine). Meta-analyses were performed in 3 comparator groups: (1) ear
      acupuncture versus sham; (2) ear acupuncture-as-adjunct to standard care; and (3)
      ear acupuncture (both as sole therapy and adjuvant) versus control to calculate
      the standardized mean difference (SMD) and weighted mean difference (WMD) for
      pain scores out of 10. Results: Six randomized controlled trials and 2
      observational studies, totaling 458 patients, were retrieved after exclusions.
      The meta-analysis used data from 4 randomized studies representing 286 patients.
      The above 3 comparator groups resulted in SMDs of 1.69, 1.68, and 1.66, and WMDs
      of 2.47, 2.84, and 2.61 respectively, all favoring acupuncture. Battlefield (ear)
      acupuncture was the most commonly used technique. There were no significant
      adverse effects and patient satisfaction improved. Results regarding if
      acupuncture reduced medication use were equivocal. Significant study bias and
      heterogeneity were found. Conclusions: While study numbers are limited, ear
      acupuncture, either as stand-alone or as-an-adjunct technique, significantly
      reduced pain scores and has potential benefits for use in the ED. Further studies
      will define acupuncture's role and if it reduces use of analgesic medications.

PMID- 29067137
TI  - Acupuncture and Cutaneous Medicine: Is It Effective?
AB  - Background: In China, acupuncture has been used as a form of medical therapy for
      more than 2500 years. It is a part of traditional medical practice and is used to
      treat the entire spectrum of human and veterinary disease. Although dermatologic
      disease has received much less attention in worldwide acupuncture research than
      pain and musculoskeletal conditions, there is a growing body of evidence
      suggesting acupuncture's usefulness in this area. Objective: The aim of this
      article was to review the evidence in the literature regarding the usefulness of
      acupuncture in managing dermatologic illness. Results: Trials and case reports of
      patients using acupuncture have been published in the areas of atopic dermatitis
      and urticaria, herpes zoster, psoriasis, acne, melasma, and hyperhidrosis, as
      well as in promoting wound healing. Itch modulation by acupuncture has been the
      focus of recent research as itch is a predominant symptom in allergic skin
      diseases and leads to serious impairment of quality of life. Conclusions:
      Although more research is needed, acupuncture's use in cutaneous medicine is
      promising in the area of itch modulation, in treating atopic dermatitis and
      herpes zoster pain, and in promoting wound healing.

PMID- 29067140
TI  - Influence of Internal Organ Pathology on Vascular Permeability of Related Skin
      Zones: An Attempt to Visualize Organ Projection Areas.
AB  - Objective: Pathology of an internal organ/body part changes electrical features
      of the corresponding skin areas-organ projection areas (OPAs)-which are often
      identified with traditional acupuncture points/zones. Once the resistance
      "breakthrough effect" has been induced in these specific skin areas,
      rectification of applied electrical currents (a diode phenomenon) occurs. In
      addition, increased impedance can be observed. It is presumed that these skin
      bioelectrical phenomena are the result of increased local capillary permeability
      with extravasation of blood-plasma albumins. Contrast-enhanced magnetic resonance
      imaging (MRI) of the microvasculature, using labeled albumins as markers, allows
      visualization of skin areas with higher albumin concentrations. The goal of this
      research was experimental verification of the abovementioned physiologic
      hypothesis by visualization of the OPAs. Materials and Methods: Preselected,
      comparative, contrast-enhanced magnetic resonance imaging (MRI) studies of the
      auricular microvasculature were performed in the Division of Diagnostic Radiology
      of Charlotte Maxeke Academic Hospital in Johannesburg, South Africa, in a group
      of 42 volunteers with proven clinical conditions of 49 (in total) chosen internal
      organs/body parts. Previously, 28 auricular OPAs related to internal organs/body
      parts with proven pathologies showed the abovementioned bioelectrical phenomena
      and 21 auricular OPAs in a control group did not show those phenomena to a
      significant extent. Contrast-enhanced MRI assessment of the study participants'
      ear auricle vascular permeability was performed after 1, 2, 3, 4, and 5 minutes
      after a standard contrast, which binds to albumins transiently, was injected
      intravenously. Contrast-enhanced magnetic resonance images of the diseased body
      part-related OPAs versus images of the same but healthy body part-related OPAs
      (control group) were subjected to a final statistical comparison. Results: It was
      presumed that 24 OPAs related to internal organs/body parts with serious
      pathologies were visualized by means of labeled albumins and 25 OPAs
      corresponding to healthy body parts or minor pathologies were not seen. OPA
      visibility depended on the extent of pathology within the related internal
      organ/body part, but not on the kind of organ/body part nor etiology or kind of
      disease. Conclusions: Pathology of internal organ/body parts appears to cause
      higher concentrations of albumins within related OPAs and, in this way, creates
      specific electrical phenomena observed at the OPAs. Contrast-enhanced MRI of the
      microvasculature, using labeled albumins, can be useful for visualizing OPAs.

PMID- 29067139
TI  - Influence of Electroacupuncture and Laser-Acupuncture on Treating Paresthesia in
      Patients Submitted to Combined Orthognathic Surgery and Genioplasty.
AB  - Objective: The goal of this research was to observe the influence of
      electroacupuncture (EA) and laser-acupuncture on the return of tactile/pain
      sensitivity in patients who underwent orthognathic surgery. Materials and
      Methods: Thirty volunteers subjected to orthognathic surgery were evaluated and
      randomly divided into 2 groups, in which 3 treatments were evaluated: control (n
      = 30) (G0, medication + placebo laser treatment) and 2 experimental treatments (n
      = 15) (G1, medication + EA) or G2 (medication + laser-acupuncture). The control
      group had n = 30 because for each experimental treatment conducted on a
      volunteer's hemi-face, there was a control treatment on the other hemi-face. In
      G1, medication was given with EA, with needles placed at predetermined points (ST
      4 [Dicang], M-HN-18 [Jiachengjiang], CV 24 [Chengjiang], ST 5 [Daying], ST 6
      [Jiache], and point A1 [YNSA]). For electrostimulation, the device used delivered
      transcutaneous electrical nerve stimulation of a burst type, with intensity and
      frequency variations of T = 220 ms and F = 4 Hz (30 minutes, 2 * /week). In G2,
      in addition to the medication, laser irradiation (at 780 nm) was applied on
      acupuncture points (at 0.04 cm2, 70 mW, 6 s/point, 0.42 J/point, 10 J/cm2, 2 *
      /week). All volunteers were evaluated before and during the 4 months following
      the surgery. Tactile sensitivity was assessed by mechanical brushing (brush #s 2
      and 12) and by a 2-point discrimination test, using a bow compass. A pain test
      was performed with a pulp electrical test that stimulates intact nerves of the
      dentin-pulp complex. A Kaplan-Meier test was performed, and survival curves were
      plotted for comparison between groups. Cox regression analysis was also conducted
      (alpha = 0.05). Results: There were no statistically significant differences
      among the groups for the 2-point discrimination test (brushes #2 and #12) on the
      buccal mucosa region and for the pulp test on all evaluated regions. However, the
      tactile test using brush #12 revealed significant differences between G1 and the
      other groups when considering the lower lip (P = 0.024) and chin (P = 0.028)
      areas. Conclusions: Only EA was able to influence-using the brushing test (brush
      #12)-the return of tactile sensitivity on the chin and lower lip positively after
      combined orthognathic surgery and genioplasty.

PMID- 29067141
TI  - Biomagnetic Pair Therapy and Typhoid Fever: A Pilot Study.
AB  - Objective: This pilot study examined the laboratory responses of patients with
      laboratory-documented typhoid fever who were treated with Biomagnetic Pair
      Therapy (BPT; medical biomagnetism), a specific application of pairs of magnets
      for various ailments that are infectious and otherwise. Materials and Methods:
      This study was an assessment of patients' response to treatment with only BPT for
      Salmonella typhi infections (typhoid fever) using standard conventional
      laboratory techniques. The research was conducted in an outpatient village clinic
      in Kenya. There were 52 participants who were evaluated for possible systemic
      illness, including typhoid fever, from an open-label study. Participants who felt
      sick and requested testing for possible typhoid fever were tested with a standard
      Widal test by a certified laboratory technician. Participants who tested positive
      (13 patients) were then treated with BPT (a "First Aid" approach) only. These
      participants then returned for follow-up laboratory and clinical evaluations
      after 2 days. Results: Most of the participants (10 of 13) retested as negative,
      and all patients reported symptomatic clinical improvement. Conclusions: As a
      significant majority of participants demonstrated clearing of their S. typhi
      after BPT, this technique should be studied further in larger trials for its
      efficacy in treating typhoid fever.

PMID- 29067142
TI  - Intermittent 96-Hour Auricular Electroacupuncture for Hot Flashes in Patients
      with Prostate Cancer: A Pilot Study.
AB  - Objective: The hot flash is a common vasomotor disorder that causes distress in
      menopausal women and that can be debilitating in men with prostate cancer who are
      treated with androgen deprivation therapy (ADT). The utility of auricular
      electroacupuncture (AEA) was tested exclusively for a small cohort of men with
      ADT-induced vasomotor symptoms while the men underwent a course of curative
      radiotherapy. Materials and Methods: Prior to and during radiotherapy treatment,
      men with vasomotor symptoms were given repeated questionnaires regarding severity
      and frequency of hot flashes, quality of life (QoL), and sleep over a 6-week span
      of an AEA protocol. Each subject's heart rate variability (HRV) was obtained
      repeatedly every week in an ambulatory setting with a BlueCardio device
      (BlueCardio, Miami, FL). The AEA intervention was given with a Neurova device
      (Nunka Corporation, CM Wellness Clinic, Pompano Beach, FL) that used three
      needles at Master points Sympathetic, Shen Men, and Point Zero, which were
      located precisely with a bipolar point finder. Intermittent microcurrent
      stimulation was given every other week for 96 hours, using a cyclic programmed
      output of 2 hours on and 2 hours off. Results: Of 10 men completing the 6-week
      protocol, all responded with significantly lower frequency, duration, and
      severity of vasomotor symptoms; QoL and sleep scores improved significantly. The
      HRV analysis showed significantly lower low-frequency/high-frequency power ratios
      in each individual, compared to baseline, that were consistent with the
      subjective responses. Conclusions: Vasomotor disturbance, caused by gender
      hormone withdrawal-either naturally or in patients treated with ADT, as in this
      study-is a well-defined neurophysiologic condition. This disorder is a
      constellation of findings that reflect autonomic disturbances of excessive
      sympathetic and reduced parasympathetic activity. AEA intervention with the
      Neurova device is simple to administer, is well-tolerated, and appears to be
      effective for restoring autonomic balance. Further evaluation of AEA for
      vasomotor disturbances could provide more insight into the mechanisms of AEA
      neuromodulation and potentially lead to approaches for treating not only these
      symptoms but also other neurologic conditions with components of autonomic
      disturbances.

PMID- 29067143
TI  - A Proposed Neurologic Pathway for Scalp Acupuncture: Trigeminal Nerve-Meninges
      Cerebrospinal Fluid-Contacting Neurons-Brain.
AB  - Objective: Scalp acupuncture is a somatic stimulation therapy that produces
      prominent clinical effects when used to treat cerebral diseases. However, this
      acupuncture's therapeutic mechanisms have not yet been well-addressed. Scalp
      acupoints are innervated by the trigeminal nerve, which is coincident with the
      intracranial sensory afferents as well as with the meningeal vessels. In recent
      years, cerebrospinal fluid-contacting neurons have been found and proved to
      transmit allergic substances between brain the parenchyma and meninges,
      representing a possible network between scalp acupuncture and the brain. The aim
      of the current study was to observe the connections between scalp acupoints and
      the meninges and to establish a possible mechanism for scalp acupuncture.
      Materials and Methods: Twenty-five adult Sprague-Dawley rats were used for the
      present study. Evans Blue dye (Sigma Chemical Co, St. Louis, MO) was injected
      though each rat's caudal vein after trigeminal stimulation for plasma
      extravasation observation. Cerebral blood flow (CBF) values of the rat's brain
      surface were measured at different timepoints before and after electroacupuncture
      (EA) on GB 15 (Toulinqi) or ST 36 (Zusanli). Results: These preliminary studies
      indicated that neurogenic plasma extravasation on a rat's skin and dura mater
      after mechanical or electrical stimulation of the trigeminal nerves is a reliable
      way to show the pathologic connection between scalp acupoints and the meninges.
      Moreover, CBF of the rat's brain surface is increased significantly after EA
      stimulation at GB 15 (Toulinqi), which is located in the receptive field of the
      supraorbital nerve. Conclusions: These findings suggest that the mechanism of
      scalp acupuncture might lie in the specific neurologic pathway that could be
      termed as trigeminal nerve-meninges-cerebrospinal fluid-contacting neurons-brain,
      which is a possible shortcut to brain functional regulation and cerebral disease
      treatment.

PMID- 29067144
TI  - Integrating Acupuncture for the Management of Costochondritis in Adolescents.
AB  - Background: Costochondritis is a common condition involving inflammation of the
      costochondral or chondrosternal joints. Conventional management of
      costochondritis includes pain medications, but these do not provide full recovery
      in all patients. There is limited information on adjunctive acupuncture for
      pediatric costochondritis. Cases: This article describes the use of acupuncture
      in the management of costochondritis in adolescent patients. A retrospective
      chart review was conducted for 3 patients who received acupuncture treatment for
      costochondritis at a tertiary pediatric medical center. Patient demographics,
      Numerical Rating Scale, and the Brief Pain Inventory were recorded. Results: All
      patients demonstrated satisfactory symptomatic reduction following acupuncture
      treatment. Conclusions: Integrating acupuncture with conventional medicine
      appeared to reduce the costochondritis symptoms in the adolescent patients.

PMID- 29067145
TI  - Electroacupuncture Therapy for Auricular Paresthesia.
AB  - Background: The great auricular nerve (GAN) provides sensory innervation to the
      skin around the auricle. Although disorder of this nerve has been reported, great
      auricular neuralgia, as reported by Blumenthal in 1992, is uncommon. The authors
      report a case of auricular paresthesia that responded well to electroacupuncture
      treatment (EAT). Case: A man in his 60s was consulted in the clinic after a 6
      month history of experiencing tingling sensations of the skin around the auricle.
      General degenerative deformity of the cervical spine was observed using computed
      radiography scans and magnetic resonance imaging; tactile hyperesthesia in the
      skin of the GAN area was also noted. This case was diagnosed as a disturbance of
      the great auricular nerve (mild neuralgia). As a potential treatment, EAT was
      administered near the affected nerve once per week for 6 weeks. Results: Visual
      analogue scale (VAS) measurements showed a marked decrease in the severity of
      this patient's symptoms, and the tactile hyperesthesia in the affected area had
      normalized. The main complaint, auricular paresthesia, had disappeared and had
      not recurred according to a check-up 15 months later. Conclusions: EAT was
      effective in the current case. It is hypothesized that EAT can reduce neural
      sensitivity via a reflex mechanism actuated by somatosensory input.

PMID- 29067147
TI  - Collagenous panenteritis: a rare cause of chronic diarrhoea.
AB  - Collagenous panenteritis is a rare inflammatory condition that causes profound
      diarrhoea and weight loss. There has only been a handful of cases reported in the
      literature. We report this rare case and the diagnostic difficulties encountered
      in securing the diagnosis. A 59-year-old woman presented with an 8-month history
      of diarrhoea and weight loss on a background of a family history of coeliac
      disease. Her presentation was complicated with acute kidney injury secondary to
      prerenal losses. Repeated gastroscopies and colonoscopies along with biopsies
      were inconclusive. It was not until histology of biopsies taken at endoscopies
      were reviewed that a diagnosis of collagenous panenteritis was secured. Her
      management revolved around combination of budesonide, gluten-free diet and
      antidiarrhoeals, which has achieved clinical remission.

PMID- 29067148
TI  - Assays for measurement of TNF antagonists in practice.
AB  - Tumour necrosis factor (TNF) antagonist drug exposure is correlated with
      clinical, endoscopic and pathophysiological outcomes during induction and
      maintenance therapy. Measuring drug concentrations is therefore a useful tool
      when treating to target and optimising therapy. One of the main factors leading
      to suboptimal drug exposure is the formation of antidrug antibodies (ADAs), due
      to an immunogenic reaction of the immune system towards the non-self protein. The
      development of ADA does pose important concerns for drug efficacy and for safety
      as ADAs have been associated with acute infusion reactions, hypersensitivity
      reactions and serum sickness. Various assays exist to measure serum drug and ADA
      concentrations, either offered as a service in a specialised laboratory or
      commercially available as a kit. It is unclear how the performance of these
      assays relates to each other, until recently various comparative studies were
      carried out. The majority of these studies show that indeed a good correlation
      exists between the assays that measure drug, but that absolute concentrations can
      differ across tests. This is particularly relevant in clinical practice when a
      specific threshold or drug concentration range is targeted. For ADA assays, drug
      sensitivity or the ability of the assay to measure ADA in the presence of drug
      remains an important issue, especially for drugs with a higher dosing frequency.
      In addition, standardisation across ADA assays is difficult, making it hard to
      compare quantitative or semiquantitative (low/medium/high) results across assays
      and across studies.

PMID- 29067149
TI  - The impact of rifaximin-alpha on the hospital resource use associated with the
      management of patients with hepatic encephalopathy: a retrospective observational
      study (IMPRESS).
AB  - OBJECTIVE: To compare all-cause and liver-related hospital resource use in the 6
      and 12 months pre-rifaximin-alpha and post-rifaximin-alpha initiation in UK
      patients with hepatic encephalopathy (HE). DESIGN: A UK multicentre,
      retrospective, observational study. Patients' medical records were reviewed for
      demographics, clinical outcomes and adverse events (AEs) to rifaximin-alpha.
      Details of hospital admissions/attendances in the 6 and 12 months pre-rifaximin
      alpha and post-rifaximin-alpha initiation were extracted from hospital electronic
      databases. SETTING: 13 National Health Service centres. PATIENTS: 207 patients
      with HE who initiated rifaximin-alpha between July 2008 and May 2014. Hospital
      resource use data were available for 145/207 patients. MAIN OUTCOME MEASURE:
      Change in mean number of liver-related hospital bed days/patient (total and
      critical care) between the 6 months pre-rifaximin-alpha and post-rifaximin-alpha
      initiation. RESULTS: Comparing the 6 months pre-rifaximin-alpha and post
      rifaximin-alpha initiation in alive patients at the end of the observation period
      (N=114): there were significant reductions in the mean number of
      hospitalisations/patient (liver-related 1.3 to 0.5, p<0.001; all-cause 1.9 to
      0.9, p<0.001), hospital bed days/patient (liver-related 17.8 to 6.8, p<0.001; all
      cause 25.4 to 10.6, p<0.001), 30-day hospital readmissions/patient (liver-related
      0.5 to 0.2, p=0.039; all-cause 0.8 to 0.4, p=0.024) and emergency department (ED)
      attendances/patient (all-cause, 1.0 to 0.5, p<0.001). The mean critical care bed
      days/patient reduced significantly for all-cause admissions (1.3 to 0.3,
      p=0.049); non-significant reduction for liver-related admissions. 4% of patients
      (9/207) developed AEs. CONCLUSIONS: In UK clinical practice, treatment with
      rifaximin-alpha for HE is well-tolerated and associated with significant
      reductions in hospitalisations, bed days (including critical care), ED
      attendances and 30-day readmissions.

PMID- 29067150
TI  - Care standards for non-alcoholic fatty liver disease in the United Kingdom 2016:
      a cross-sectional survey.
AB  - OBJECTIVE: Guidelines for the assessment of non-alcoholic fatty liver disease
      (NAFLD) have been published in 2016 by National Institute for Health and Care
      Excellence and European Associations for the study of the Liver-European
      Association for the study of Diabetes-European Association for the study of
      Obesity. Prior to publication of these guidelines, we performed a cross-sectional
      survey of gastroenterologists and hepatologists regarding NAFLD diagnosis and
      management. DESIGN: An online survey was circulated to members of British
      Association for the Study of the Liver and British Society of Gastroenterology
      between February 2016 and May 2016. RESULTS: 175
      gastroenterologists/hepatologists responded, 116 completing the survey,
      representing 84 UK centres. 22% had local NAFLD guidelines. 45% received >300
      referrals per year from primary care for investigation of abnormal liver function
      tests (LFTs). Clinical assessment tended to be performed in secondary rather than
      primary care including body mass index (82% vs 26%) and non-invasive liver screen
      (86% vs 32%) and ultrasound (81% vs 37%). Widely used tools for non-invasive
      fibrosis risk stratification were aspartate transaminase (AST)/alanine
      transaminase (ALT) ratio (53%), Fibroscan (50%) and NAFLD fibrosis score (41%).
      78% considered liver biopsy in selected cases. 50% recommended 10% weight loss
      target as first-line treatment. Delivery of lifestyle interventions was mostly
      handed back to primary care (56%). A minority have direct access to community
      weight management services (22%). Follow-up was favoured by F3/4 fibrosis
      (72.9%), and high-risk non-invasive fibrosis tests (51%). Discharge was favoured
      by simple steatosis at biopsy (30%), and low-risk non-invasive scores (25%).
      CONCLUSIONS: The survey highlights areas for improvement of service provision for
      NAFLD assessment including improved recognition of non-alcoholic steatohepatitis
      in people with type 2 diabetes, streamlining abnormal LFT referral pathways,
      defining non-invasive liver fibrosis assessment tools, use of liver biopsy,
      managing metabolic syndrome features and improved access to lifestyle
      interventions.

PMID- 29067151
TI  - Primary sclerosing cholangitis and the management of uncertainty and complexity.
AB  - Primary sclerosing cholangitis (PSC) is a rare chronic autoimmune disease with no
      effective therapy and a large unmet need for new treatments. Patients require
      significant healthcare resources over their lifetime with high rates of hospital
      admission, malignancy, liver transplantation and death. As a rare disease,
      expertise in management can be limited to large referral liver transplant
      programmes, and even then there is frequently variation in practice. In this case
      based review, we aim to discuss common clinical dilemmas encountered by
      clinicians managing patients with PSC and address related competencies in the
      2010 Gastroenterology Curriculum.

PMID- 29067152
TI  - Are patients in the IBD clinic at risk of proctitis secondary to sexually
      transmitted infections?
AB  - OBJECTIVE: To gauge the potential risk of sexually transmitted infection (STI) as
      a cause of proctitis in a cohort of patients with inflammatory bowel disease
      (IBD) and to gauge whether this cohort could benefit from STI testing in the
      future. DESIGN: Patients attending the IBD clinic were given an anonymous
      questionnaire recording demographics, sexual behaviour, rectal symptoms, history
      of receptive anal intercourse (RAI), STIs and attitudes towards sexual health
      screening. SETTING: A gastroenterology teaching hospital IBD clinic. PATIENTS:
      280 consecutive patients attending a teaching hospital IBD clinic over a
      consecutive 6-week period. All patients had an endoscopic, radiological and/or
      histological diagnosis of IBD. RESULTS: 280 questionnaires were distributed and
      274 analysed (3 incomplete, 2 not returned, 1 no sexual activity). 167 female
      (median: 46 years, range 17-81 years) and 107 males. Two males disclosed RAI and
      were used as a control. Of the 167 females, 96% were heterosexual, 2.4% were same
      sex partners and 1.2% were bisexual. 14% had a history of RAI-this group had more
      previous STIs (40%) versus those with no history RAI (5%) (p<0.0001; relative
      risk (RR) 13.41). Chronic rectal pain was more frequent in women with RAI (RR
      2.4; p<=0.03). No difference in rectal discharge (RR 1.75; p=0.72) or bleeding
      (p=0.3). CONCLUSIONS: This is the first report of sexual behaviours in a non
      genitourinary medicine clinic; giving a unique insight into sexual practices in a
      cohort of patients with IBD. A past history of STI and RAI can identify risk and
      we propose testing for those with a history of STI, RAI, men who have sex with
      men and women aged under 25 years.

PMID- 29067153
TI  - Implementing a self-management strategy in inflammatory bowel disease (IBD):
      patient perceptions, clinical outcomes and the impact on service.
AB  - INTRODUCTION: Patient self-management and its service integration is not a new
      concept but it may be a key component in the long-term sustainability of
      inflammatory bowel disease (IBD) service provision, when considering growing
      disease prevalence and limited resources. METHODS: The IBD team at the Royal
      Alexandra and Vale of Leven Hospitals in the Clyde Valley region developed a self
      management tool, called the 'flare card'. Patients were asked to complete a
      questionnaire which reflected their opinion on its viability as a self-management
      intervention. In addition, its utility in terms of service use over a 10-month
      period in 2016 was compared with a similar cohort of patients over 10 months in
      2015. RESULTS: Patients overall felt that the 'flare card' was a viable self
      management tool. Positive feedback identified that the intervention could help
      them aid control over their IBD, improve medication adherence, reduce symptoms
      and reflected a feeling of patient-centred IBD care. The comparison between 2015
      and 2016 service use revealed a significant reduction in IBD and non-IBD service
      usage, Steroid prescribing and unscheduled IBD care in the flare card supported
      cohort. CONCLUSIONS: IBD services must continue to adapt to changes within the
      National Health Service bearing in mind long-term sustainability and continued
      care provision. The 'flare card' goes further in an attempt to optimise Crohn's
      disease and ulcerative colitis management by harmonising clinician evaluation and
      patient's self-initiation of therapy and investigation.

PMID- 29067154
TI  - A positive SeHCAT test results in fewer subsequent investigations in patients
      with chronic diarrhoea.
AB  - : Chronic diarrhoea is a common condition, resulting from a number of different
      disorders. Bile acid diarrhoea, occurring in about a third of these patients, is
      often undiagnosed. We hypothesised that a positive diagnosis of bile acid
      diarrhoea would reduce the need for subsequent investigations for alternative
      diagnoses. METHODS: Patients previously recruited to a study of chronic diarrhoea
      who had selenium homocholic acid taurine (SeHCAT) testing and subsequent follow
      up at our institution were identified. In a retrospective analysis, the numbers
      of defined investigations undertaken from the first 3 months after SeHCAT in the
      following 5 years were compared. RESULTS: 90 patients were identified with
      primary bile acid diarrhoea (SeHCAT retention <15%, n=36) or idiopathic diarrhoea
      (SeHCAT retention >15%, n=54). Follow-up had been performed on 29 and 39
      subjects, respectively, with no differences in previous investigations or the
      last contact date. In the follow-up period, the proportions of these patients who
      had undergone endoscopic procedures (gastroscopy, colonoscopy and sigmoidoscopy)
      were the same. However, there was a higher proportion of patients in the SeHCAT
      negative group who had other investigations, including imaging, physiological
      tests and blood tests (p=0.037). The use of cross-sectional imaging was
      significantly higher in this group (p=0.015) with greater proportions having CT
      (0.44 vs 0.10) and MRI (0.26 vs 0.07). Ultrasound use and the number of blood
      tests were higher in the SeHCAT-negative group whereas the SeHCAT-positive group
      attended more clinic appointments (p=0.013). CONCLUSION: A positive diagnosis of
      bile acid diarrhoea, made by a SeHCAT test, resulted in reduced use of diagnostic
      investigations over the subsequent 5 years.

PMID- 29067155
TI  - The 2015 upper gastrointestinal "Be Clear on Cancer" campaign: its impact on
      gastroenterology services and malignant and premalignant diagnoses.
AB  - OBJECTIVE: To assess the impact of the upper gastrointestinal 'Be Clear on
      Cancer' campaign launched by Public Health England between January and February
      2015 on open-access gastroscopy referrals, incidence of target diagnoses
      (oesophagogastric cancer and Barrett's oesophagus), cancer staging at
      presentation, 1-year survival and cost per additional diagnosis. DESIGN: We
      performed a retrospective study of patients referred for 2-week-wait (2WW), open
      access endoscopy 3 months following the campaign with diagnoses, endoscopic
      findings, staging and 12-month survival compared with data from corresponding
      months in 2014. SETTING: Three adjacent National Health Service trusts in the
      West Midlands with a combined population of 1.34 million in 2015. RESULTS: 2WW
      open-access referrals increased by 48% (95% CI 1.35 to 1.61, p<0.001). The
      proportion of target diagnoses fell from 6.7% to 6.1% (p=0.62). There were no
      significant overall increases in target diagnoses (OR 1.35, 95% CI 0.95 to 1.92,
      p=0.11) or cancer (OR 1.30, 95% CI 0.80 to 2.07, p=0.36). There was no change in
      tumour, node, metastasis (TNM) staging for oesophageal or gastric cancer. Overall
      1-year survival did not alter significantly (HR 1.10, 95% CI 0.56 to 2.19,
      p=0.76). DISCUSSION: The 'Be Clear on Cancer' campaign led to a 48% increase in
      demand for 2WW gastroscopies but did not significantly affect the incidence of
      target diagnoses, cancer staging or 1-year survival.

PMID- 29067156
TI  - The National Oesophagogastric Cancer Awareness Campaign: a locality outcome
      analysis from County Durham.
AB  - INTRODUCTION: Oesophageal and gastric cancer is common. Despite advances in
      investigation and treatment, the outcomes from these cancers remain poor. As part
      of the Be Clear On Cancer Campaign, the Department of Health runs the National
      Oesophagogastric Cancer Campaign each year, with key messages of (1) 'Having
      heartburn most days, for 3 weeks or more could be a sign of cancer' and (2) 'if
      food is sticking when you swallow, tell your doctor'. METHODS: We evaluated the
      effect of the National Oesophagogastric Cancer Campaign in our locality. RESULTS:
      Reviewing new referrals from primary care for upper gastrointestinal symptoms
      during the campaign period, and a period thereafter, we found that there was no
      significant impact of the campaign in the diagnosis of oesophagogastric cancers.
      Furthermore, it increased routine waiting times for elective gastroscopies in our
      endoscopy units. CONCLUSION: We believe that alternative strategies need to be
      considered for earlier detection of oesophagogastric cancer.

PMID- 29067157
TI  - Guide to managing persistent upper gastrointestinal symptoms during and after
      treatment for cancer.
AB  - BACKGROUND: Guidance: the practical management of the gastrointestinal symptoms
      of pelvic radiation disease was published in 2014 for a multidisciplinary
      audience. Following this, a companion guide to managing upper gastrointestinal
      (GI) consequences was developed. AIMS: The development and peer review of an
      algorithm which could be accessible to all types of clinicians working with
      patients experiencing upper GI symptoms following cancer treatment. METHODS:
      Experts who manage patients with upper GI symptoms were asked to review the
      guide, rating each section for agreement with the recommended measures and
      suggesting amendments if necessary. Specific comments were discussed and
      incorporated as appropriate, and this process was repeated for a second round of
      review. RESULTS: 21 gastroenterologists, 11 upper GI surgeons, 9 specialist
      dietitians, 8 clinical nurse specialists, 5 clinical oncologists, 3 medical
      oncologists and 4 others participated in the review. Consensus (defined
      prospectively as 60% or more panellists selecting 'strongly agree' or 'agree')
      was reached for all of the original 31 sections in the guide, with a median of
      90%. 85% of panellists agreed that the guide was acceptable for publication or
      acceptable with minor revisions. 56 of the original 61 panellists participated in
      round 2. 93% agreed it was acceptable for publication after the first revision.
      Further minor amendments were made in response to round 2. CONCLUSIONS: Feedback
      from the panel of experts developed the guide with improvement of occasional
      algorithmic steps, a more user-friendly layout, clearer time frames for referral
      to other teams and addition of procedures to the appendix.

PMID- 29067158
TI  - Proof of concept: short-term non-invasive cervical vagus nerve stimulation in
      patients with drug-refractory gastroparesis.
AB  - BACKGROUND: Gastric electric stimulation (GES) is a treatment approach to
      refractory gastroparesis, possibly acting centrally via afferent vagus nerve
      stimulation (VNS). Non-invasive VNS (nVNS) is a potential alternative to GES that
      could eliminate the safety risks of or identify likely responders to implantable
      neurostimulators. OBJECTIVE: This open-label proof-of-concept study assessed the
      effects of nVNS in patients with severe drug-refractory gastroparesis. METHODS:
      Patients used the Gastroparesis Cardinal Symptom Index (GCSI) to grade symptoms
      in diaries daily for 2 weeks before treatment (baseline) and during >=3 weeks of
      nVNS therapy. Adverse events (AEs) were also diarised. Treatment was self
      administered using an nVNS device (gammaCore, electroCore) and consisted of 120 s
      stimulations to the vagus nerve in the neck (two stimulations to each side three
      times daily during weeks 1 and 2; three stimulations to each side three times
      daily during week 3 and beyond). Response was defined as a >=1 point decrease
      from baseline in GCSI score. RESULTS: Thirty-five patients enrolled; 23 were
      compliant with study procedures and were included in the analysis; 7 continued
      treatment beyond 3 weeks. Response rates were 35% (8/23) at 3 weeks and 43%
      (10/23) for the duration of therapy (3-6 weeks). For the entire cohort and the 10
      responders, improvements from baseline were noted for mean total GCSI and GCSI
      subscale scores (nausea/vomiting, postprandial fullness/early satiety, bloating).
      No serious AEs were reported. CONCLUSIONS: These preliminary results provide a
      signal that nVNS may be useful for treating refractory gastroparesis. Larger
      controlled studies are warranted.

PMID- 29067159
TI  - Null hypothesis significance testing: a short tutorial.
AB  - Although thoroughly criticized, null hypothesis significance testing (NHST) is
      the statistical method of choice in biological, biomedical and social sciences to
      investigate if an effect is likely. In this short tutorial, I first summarize the
      concepts behind the method while pointing to common interpretation errors. I then
      present the related concepts of confidence intervals, and discuss what should be
      reported in which context. The goal is to clarify concepts, present statistical
      issues that researchers face using the NHST framework and propose reporting
      practices.

PMID- 29067160
TI  - Case Report: Application of whole exome sequencing for accurate diagnosis of rare
      syndromes of mineralocorticoid excess.
AB  - Syndromes of mineralocorticoid excess (SME) are closely related clinical
      manifestations occurring within a specific set of diseases. Overlapping clinical
      manifestations of such syndromes often create a dilemma in accurate diagnosis,
      which is crucial for disease surveillance and management especially in rare
      genetic disorders. Here we demonstrate the use of whole exome sequencing (WES)
      for accurate diagnosis of rare SME and report that p.R337C variation in the
      HSD11B2 gene causes progressive apparent mineralocorticoid excess (AME) syndrome
      in a South Indian family of Mappila origin.

PMID- 29067161
TI  - Case Report: Whole exome sequencing identifies variation c.2308G>A p.E770K in
      RAG1 associated with B- T- NK+ severe combined immunodeficiency.
AB  - Severe combined immunodeficiency is a large clinically heterogeneous group of
      disorders caused by a defect in the development of humoral or cellular immune
      responses. At least 13 genes are known to be involved in the pathophysiology of
      the disease and the mutation spectrum in SCID have been well documented. The
      widespread application of whole-exome sequencing based on next-generation
      sequencing has offered a new opportunity to systematically screen these genes in
      clinical scales. In this report, we describe the application of whole exome
      sequencing for arriving at a molecular diagnosis in a child suffering from B- T-
      NK+ severe combined immunodeficiency. Apart from making the accurate molecular
      diagnosis, we also add a genetic variation c.2308G>A p.E770K to the compendium of
      variations associated with the disease.

PMID- 29067162
TI  - Transcriptomic analysis of Saccharomycescerevisiae x Saccharomyces kudriavzevii
      hybrids during low temperature winemaking.
AB  - BACKGROUND: Although Saccharomyces cerevisiae is the most frequently isolated
      species in wine fermentation, and the most studied species, other species and
      interspecific hybrids have greatly attracted the interest of researchers in this
      field in the last few years, given their potential to solve new winemaking
      industry challenges. S. cerevisiae x S. kudriavzevii hybrids exhibit good
      fermentative capabilities at low temperatures, and produce wines with smaller
      alcohol quantities and larger glycerol quantities, which can be very useful to
      solve challenges in the winemaking industry such as the necessity to enhance the
      aroma profile. METHODS: In this study, we performed a transcriptomic study of S.
      cerevisiae x S. kudriavzevii hybrids in low temperature winemaking conditions.
      RESULTS: The results revealed that the hybrids have acquired both fermentative
      abilities and cold adaptation abilities, attributed to S. cerevisiae and S.
      kudriavzevii parental species, respectively, showcasing their industrially
      relevant characteristics. For several key genes, we also studied the contribution
      to gene expression of each of the alleles of S. cerevisiae and S. kudriavzevii in
      the S. cerevisiae x S. kudriavzevii hybrids. From the results, it is not clear
      how important the differential expression of the specific parental alleles is to
      the phenotype of the hybrids. CONCLUSIONS: This study shows that the fermentative
      abilities of S. cerevisiae x S. kudriavzevii hybrids at low temperatures do not
      seem to result from differential expression of specific parental alleles of the
      key genes involved in this phentoype.

PMID- 29057069
TI  - Giving eyespots a shiner: Pharmacologic manipulation of the Io moth wing pattern.
AB  - Our knowledge of wing pattern formation in Lepidoptera has advanced significantly
      in recent years due to the careful examination of several groups of butterflies.
      The eyespot is a prominent feature of Lepidoptera wing pattern, especially in the
      family Saturniidae. The present study examined how sulfated polysaccharides
      affected the wing pattern formation of the Io moth, Automeris io (Saturniidae). 
      Prepupae and pupae of this species were subjected to injections of heparin and
      cold shock. While the cold shock had little to no effect on wing pattern, the
      aberrations resulting from heparin injections were moderate to profound and
      depended on the dose and the stage at which injection was made. The changes
      consisted of expansion of the black ring around the dorsal hindwing eyespots and
      distortion of discal spots on both dorsal and ventral sides of forewings,
      suggesting a possible link between genetic controls of these elements. Several
      different types of scales form the normal color pattern of Automeris io, and
      heparin-induced changes correspond to changes in shape of scales. The resulting
      aberrations are dubbed 'Black Eye' and 'Comet Eye.' Other known aberrations of
      Automeris io eyespots are summarized, illustrated, and named.

PMID- 29067164
TI  - A case series report of cancer patients undergoing group body psychotherapy.
AB  - Background: Disturbances in bodily wellbeing represent a key source of
      psychosocial suffering and impairment related to cancer. Therefore, interventions
      to improve bodily wellbeing in post-treatment cancer patients are of paramount
      importance. Notably, body psychotherapy (BPT) has been shown to improve bodily
      wellbeing in subjects suffering from a variety of mental disorders. However, how
      post-treatment cancer patients perceive and subjectively react to group BPT
      aiming at improving bodily disturbances has, to the best of our knowledge, not
      yet been described. Methods: We report on six patients undergoing outpatient
      group BPT that followed oncological treatment for malignant neoplasms. The BPT
      consisted of six sessions based on a scientific embodiment approach, integrating
      body-oriented techniques to improve patients' awareness, perception, acceptance,
      and expression regarding their body. Results: The BPT was well accepted by all
      patients. Despite having undergone different types of oncological treatment for
      different cancer types and locations, all subjects reported having appreciated
      BPT and improved how they perceived their bodies. However, individual
      descriptions of improvements showed substantial heterogeneity across subjects.
      Notably, most patients indicated that sensations, perceptions, and other mental
      activities related to their own body intensified when proceeding through the
      group BPT sessions. Conclusion: The findings from this case series encourage and
      inform future studies examining whether group BPT is efficacious in post
      treatment cancer patients and investigating the related mechanisms of action. The
      observed heterogeneity in individual descriptions of perceived treatment effects
      point to the need for selecting comprehensive indicators of changes in
      disturbances of bodily wellbeing as the primary patient-reported outcome in
      future clinical trials. While increases in mental activities related to their own
      body are commonly interpreted as important mechanisms of therapeutic action in
      BPT, follow-up assessments are needed to evaluate intended and unintended
      consequences of these changes in cancer patients.

PMID- 29067166
TI  - The potential adoption benefits and challenges of LOINC codes in a laboratory
      department: a case study.
AB  - BACKGROUND: Logical Observation Identifiers Names and Codes (LOINC) are a
      standard for identifying and reporting laboratory investigations that were
      developed and are maintained by the Regenstrief Institute. LOINC codes have been
      adopted globally by hospitals, government agencies, laboratories, and research
      institutions. There are still many healthcare organizations, however, that have
      not adopted LOINC codes, including rural hospitals in low- and middle- income
      countries. Hence, organizations in these areas do not receive the benefits that
      accrue with the adoption of LOINC codes. METHODS: We conducted a literature
      search by utilizing PubMed, CINAHL, Google Scholar, ACM Digital Library, and the
      Biomed Central database to look for existing publications on the benefits and
      challenges of adopting LOINC. We selected and reviewed 16 publications and then
      conducted a case study via the following steps: (1) we brainstormed, discussed,
      analyzed, created and revised iteratively the patient's clinical encounter
      (outpatient or ambulatory settings) process within a laboratory department via
      utilizing a hypothetical patient; (2) we incorporated the work experience of one
      of the authors (CU) in a rural hospital laboratory department in Nigeria to break
      down the clinical encounter process into simpler and discrete steps and created a
      series of use cases for the process; (3) we then analyzed and summarized the
      potential usage of LOINC codes (clinically, administratively, and operationally)
      and the benefits and challenges of adopting LOINC codes in such settings by
      examining the use cases one by one. RESULTS: Based on the literature review, we
      noted that LOINC codes' ability to improve laboratory results' interoperability
      has been recognized broadly. LOINC-coded laboratory results can improve patients'
      safety due to their consistent meaning as well as the related reduction of
      duplicate lab tests, easier assessment of workloads in the laboratory
      departments, and accurate auditing of laboratory accounts. Further, the adoption
      of LOINC codes may motivate government agencies to upgrade hospitals'
      infrastructures, which could increase the possibility of international
      recognition of laboratory test results from those hospitals over the long term.
      Meanwhile, a lack of LOINC codes in paper format and a lack of LOINC codes
      experts are major challenges that may limit LOINC adoption. CONCLUSION: In this
      paper, we intend to provide a snapshot of the possible usage of LOINC codes in
      rural hospitals in low- and middle-income countries via simpler and detailed use
      cases. Our analysis may aid policymakers to gain a deeper understanding of LOINC
      codes in regard to clinical, administrative, and operational aspect and to make
      better-informed decisions in regard to LOINC codes adoption. The use case
      analysis also can be used by information system designers and developers to
      reference workflow within a laboratory department. We recognize that this
      manuscript is only a case study and that the exact steps and workflows may vary
      in different laboratory departments; however, the core steps and main benefits
      should be consistent.

PMID- 29067167
TI  - Access is Open.

PMID- 29067168
TI  - Seven common mistakes to avoid in achieving long-term success with dermatology
      patients.
AB  - Managing a pet's chronic dermatologic conditions can be frustrating for both
      clients and clinicians, but there are steps to making the process easier for
      everyone. Avoid the following seven mistakes sometimes made in managing
      dermatology cases and you will find the process considerably easier in the
      future.

PMID- 29067165
TI  - Recent Advances in Understanding Cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is an aggressive malignancy that arises from damaged
      epithelial cells, cholangiocytes, and possibly de-differentiated hepatocytes. CCA
      has a poor overall survival rate and limited therapeutic options. Based on this
      data, it is imperative that new diagnostic and therapeutic interventions be
      developed. Recent work has attempted to understand the pathological mechanisms
      driving CCA progression. Specifically, recent publications have delved into the
      role of cancer stem cells (CSCs), mesenchymal stem cells (MSCs), and microRNAs
      (miRNAs) during CCA pathology. CSCs are a specific subset of cells within the
      tumor environment that are derived from a cell with stem-like properties and have
      been shown to influence recurrence and chemoresistance during CCA. MSCs are known
      for their anti-inflammatory activity and have been postulated to influence
      malignancy during CCA, but little is known about their exact functions. miRNAs
      exert various functions via gene regulation at both the transcriptional and the
      translational levels, giving miRNAs diverse roles in CCA progression.
      Additionally, current miRNA-based therapeutic approaches are in clinical trials
      for various liver diseases, giving hope for similar approaches for CCA. However,
      the interactions among these three factors in the context of CCA are unknown. In
      this review, we focus on recently published data (within the last 3 years) that
      discuss the role of CSCs, MSCs, and miRNAs and their possible interactions during
      CCA pathogenesis.

PMID- 29067169
TI  - Prevalence of carcass bruises as an indicator of welfare in beef cattle and the
      relation to the economic impact.
AB  - The objective of this work was to characterize bruises in bovine carcasses in
      Uruguay and to evaluate the economic impact. Thirteen abattoirs were visited
      during 2 years and bruises were identified, classified, and quantified by zone
      and degree (depth and size). One hundred carcasses were separated and bruises
      were cut out and weighed separately. From a total of 15 157 carcasses observed,
      60.0% had at least one bruise; 42.0% of these had bruises on both sides. The
      expensive butt zone was the most damaged, followed by rib, shoulder and loin,
      respectively. The mean weight and standard error of the condemned trimmed meat
      was 1602 +/- 212 g. It suppose a loss of 899 g per animal slaugtered in Uruguay.
      In a country sending 2.5 million heads of cattle to be slaughter yearly, this
      indicates an important financial loss. Improving transport conditions and
      personnel skills will probably result in a better welfare for the animals as well
      as better financial profit.

PMID- 29067170
TI  - Efficacy of glucocorticoid monotherapy for treatment of canine
      meningoencephalomyelitis of unknown etiology: a prospective study in 16 dogs.
AB  - Canine non-infectious, inflammatory meningoencephalomyelitis is termed
      meningoencephalomyelitis of unknown etiology (MUE) and may affect dogs of any
      age, breed or gender. Treatment with immunosuppressive medication has been widely
      reported, however no prospective clinical trials with a standard glucocorticoid
      monotherapy are available. The objectives were to compare the cerebrospinal fluid
      (CSF) analysis at diagnosis and after treatment with a standard glucocorticoid
      (GC) dose and to determine the survival time in dogs with MUE. We hypothesized
      that abnormal CSF findings would normalize in dogs with MUE, and survival time
      would be longer than previously reported for glucocortocoid therapy alone.
      Inclusion criteria were: (1) normal minimum database, (2) no GC use within 5
      days, (3) magnetic resonance imaging performed, (4) negative infectious disease
      titres, and (5) abnormal CSF analysis. All dogs received GC therapy at 1 mg/kg
      per os q 12 h. Responders had normal CSF analysis at 1 month. Sixteen dogs met
      the inclusion criteria. Median total nucleated cell count (TNCC) and protein
      concentration at time of diagnosis were 39 cells/MUL (0-1400 cells/MUL), and 49
      mg/dL (25-293 mg/dL), respectively. Median TNCC and protein concentration at 1
      month were 1 cell/MUL (0-120 cells/MUL), and 24 mg/dL (13-175 mg/dL),
      respectively. Seven of 16 dogs (44%) were responders. There was no significant
      difference in survival between the CSF responders and CSF non-responders (P =
      0.85). Overall median survival was 602 days (45-654 days). This study supports
      using GC therapy in dogs with MUE.

PMID- 29067172
TI  - Influence of the dietary fibre levels on faecal hair excretion after 14 days in
      short and long-haired domestic cats.
AB  - Hairballs are a common problem in cats and may result in intestinal obstruction.
      Dietary fibre has been recommended to stimulate hair faecal excretion. The
      objective of this study was to assess the influence of psyllium and different
      levels of total dietary fibre (6% vs. 11% vs. 15% TdF) on hair faecal excretion
      in short and long-haired (LH) domestic cats. Twenty-one adult cats were divided
      into three panels: shedding panel, short-haired (SH) panel and LH panel. Shedding
      panel was used to assess shedding throughout the study with a normalized
      brushing. In parallel, SH panel and LH panel were used to evaluate the impact of
      the diets on faecal hair excretion. They were fed a low-fibre diet during phase 1
      (diet 6, 6.0% TdF). In phase 2, panels were fed either diet 11 (11% TdF) or diet
      15 (15% TdF). In phase 3, cats returned to diet 6 before a crossover on the other
      diet in phase 4. Those diets were fed to cats for 14 days. Faecal hair excretion
      was quantified daily. Data were analysed using a generalized linear model
      procedure. The assessment of shedding showed that the study did not occur during
      moulting season. In the LH panel, diet 11 and diet 15 increased (P < 0.001)
      faecal hair excretion by 81% and 113% respectively, compared to the control diet.
      In the SH panel, no influence of the diets was observed. This study supports that
      fibre affects faecal hair excretion in LH cats, suggesting that a diet with
      psyllium and 11% or 15% TdF might minimize hairball formation in 14 days and
      between shedding periods. In SH cats, 11% and 15% fibre levels had no effect on
      faecal hair excretion. This could be explained by the low quantity of hair
      ingested outside the shedding season or by the short duration of the study.

PMID- 29067171
TI  - Porcine cytomegalovirus infection is not associated to the occurrence of post
      weaning multisystemic wasting syndrome.
AB  - Porcine cytomegalovirus (PCMV) is a Betaherpesvirus that causes lifelong latent
      infections in swine; occasionally, it may be associated with inclusion body
      rhinitis in piglets and reproductive disorders in pregnant sows. Post-weaning
      multisystemic wasting syndrome (PMWS) a condition where porcine circovirus type 2
      (PCV2) infection is necessary - though not sufficient - to trigger disease, has
      become one of the major health problems to the porcine productive chain. Despite
      the high expected prevalence of both PCMV and PCV2 in swine-raising farms, no
      links between PCMV and PMWS have been investigated so far. In view of that, the
      present study was conducted to search for relations between PCMV infections and
      the occurrence of PMWS. Spleen and sera of PMWS-affected and non-PWMS-affected
      animals were examined. In PMWS-affected animals, PCMV DNA was detected in 88.4%
      of the spleen samples and 7.6% of the sera, whereas in non-PMWS-affected pigs,
      PCMV DNA was detected in 72.7% of the spleens and 10% of sera. Such differences
      were not statistically significant. These findings showed despite the high
      prevalence of PCMV infections in the swine population examined, no positive or
      negative association could be inferred from the presence of PCMV DNA and the
      occurrence of PMWS.

PMID- 29067173
TI  - Use of a perineural coiled catheter at the sciatic nerve in dogs after tibial
      plateau levelling osteotomy - preliminary observations.
AB  - The analgesic effects of peripheral nerve blocks can be prolonged with the
      placement of perineural catheters allowing repeated injections of local
      anaesthetics in humans. The objectives of this study were to evaluate the
      clinical suitability of a perineural coiled catheter (PCC) at the sciatic nerve
      and to evaluate pain during the early post-operative period in dogs after tibial
      plateau levelling osteotomy. Pre-operatively, a combined block of the sciatic and
      the femoral nerves was performed under sonographic guidance (ropivacaine 0.5%;
      0.3 mL kg-1 per nerve). Thereafter, a PCC was placed near the sciatic nerve.
      Carprofen (4 mg kg-1 intravenously) was administered at the end of anaesthesia.
      After surgery, all dogs were randomly assigned to receive four injections of
      ropivacaine (group R; 0.25%, 0.3 mL kg-1) or NaCl 0.9% (group C; 0.3 mL kg-1)
      every 6 h through the PCC. Pain was assessed by use of a visual analogue scale
      (VAS) and a multi-dimensional pain score (4Avet) before surgery (T-1), for 390
      min (T0, T30, T60, T120, T180, T240, T300, T360 and T390) as well as 1 day after
      surgery (Day 1). Methadone (0.1 mg kg-1) was administered each time the VAS was
      >=40 mm or the 4Avet was >=5. At T390 dogs received buprenorphine (0.02 mg kg-1).
      Data were compared using Mann-Whitney rank sum tests and repeated measures
      analysis of variance. Regardless of group allocation, 55% of dogs required
      methadone. VAS was significantly lower at T390 (P = 0.003), and at Day 1 (P =
      0.002) and so was 4Avet at Day 1 (P = 0.012) in group R than in group C. Bleeding
      occurred in one dog at PCC placement and PCC dislodged six times of 47 PCCs
      placed. Minor complications occurred with PCC but allowed four repeated
      administrations of ropivacaine or saline over 24 h in 91.5% of the cases.

PMID- 29067174
TI  - Outcome and toxicity assessment of feline small cell lymphoma: 56 cases (2000
      2010).
AB  - Feline small cell lymphoma is associated with greater response to treatment and
      survival when compared to large cell lymphoma. Treatment-associated toxicity,
      response to rescue chemotherapy and prognostic factors are largely unknown. This
      retrospective study was performed to identify treatment-associated toxicity,
      response to rescue chemotherapy and treatment outcome for cats diagnosed with
      small cell lymphoma of various anatomic locations. Medical records from 56 cats
      were evaluated. All cats were treated with glucocorticoid and chlorambucil with
      discontinuation of treatment recommended at 1 year if complete clinical response
      was documented. Chemotherapy toxicity was uncommon (33.9%) and generally mild.
      Grade III or IV hepatotoxicity was documented in 10.7% of patients. Overall
      response rate was 85.7% with glucocorticoid and chlorambucil. Median progression
      free survival was 1078 days. Overall response rate for rescue chemotherapy was
      59%. Reintroduction of prednisone and chlorambucil was associated with
      significantly longer survival than prednisone and lomustine (>1500 vs. 492 days,
      P = 0.01). Median overall survival times for cats with lymphoma of the
      gastrointestinal tract was not significantly different from those with extra
      intestinal disease locations (1148 vs. 1375 days, P = 0.23). Median overall
      survival was 1317 days. Toxicity, other than hepatotoxicity was mild. Rescue
      chemotherapy with re-introduction of glucocorticoids and chlorambucil was most
      successful. Discontinuation of glucocorticoid and chlorambucil with subsequent
      reintroduction as rescue chemotherapy appears to be just as effective as
      continued administration in cats.

PMID- 29067175
TI  - Pharmacokinetic-pharmacodynamic integration of enrofloxacin and its metabolite
      ciprofloxacin in buffalo calves.
AB  - The present study was planned with an objective to test the pharmacokinetics of a
      new formulation of enrofloxacin (Flobac(r) SA) in buffalo calves. The drug was
      administered at the dose rate of 7.5 mg kg-1 body weight through the intravenous
      (i.v.) and intramuscular (i.m.) route followed by plasma collection and analysis
      at different time intervals. After analysis, using High Performance Liquid
      Chromatography - Ultraviolet, various pharmacokinetic parameters were calculated
      using visual fit for compartmental analysis, followed by integration with
      pharmacodynamic parameters against Escherichia coli and Pasteurella multocida.
      Although total area under plasma drug concentration time curve was higher through
      the i.v. route, mean residence time and metabolic conversion ratio was higher
      following administration by the i.m. route indicating longer persistence of the
      drug in body. Overall i.m. bioavailability of the parent compound with its
      metabolite was found to be 91%. Upon, Pharmacokinetic-Pharmacodynamic
      integration, all the parameters indicated significant antibacterial activity. It
      can be concluded that the dose of enrofloxacin used in the present study can be
      administered to contain infections caused by P. multocida and E. coli in buffalo
      calves.

PMID- 29067176
TI  - Grapiprant: an EP4 prostaglandin receptor antagonist and novel therapy for pain
      and inflammation.
AB  - There are five active prostanoid metabolites of arachidonic acid (AA) that have
      widespread and varied physiologic functions throughout the body, including
      regulation of gastrointestinal mucosal blood flow, renal haemodynamics and
      primary haemostasis. Each prostanoid has at least one distinct receptor that
      mediates its action. Prostaglandin E2 (PGE 2) is a prostanoid that serves
      important homeostatic functions, yet is also responsible for regulating pain and
      inflammation. PGE 2 binds to four receptors, of which one, the EP4 receptor, is
      primarily responsible for the pain and inflammation associated with
      osteoarthritis (OA). The deleterious and pathologic actions of PGE 2 are
      inhibited in varying degrees by steroids, aspirin and cyclo-oxygenase inhibiting
      NSAIDs; however, administration of these drugs causes decreased production of PGE
      2, thereby decreasing or eliminating the homeostatic functions of the molecule.
      By inhibiting just the EP4 receptor, the homeostatic function of PGE 2 is better
      maintained. This manuscript will introduce a new class of pharmaceuticals known
      as the piprant class. Piprants are prostaglandin receptor antagonists (PRA). This
      article will include basic physiology of AA, prostanoids and piprants, will
      review available evidence for the relevance of EP4 PRAs in rodent models of pain
      and inflammation, and will reference available data for an EP4 PRA in dogs and
      cats. Piprants are currently in development for veterinary patients and the
      purpose of this manuscript is to introduce veterinarians to the class of drugs,
      with emphasis on an EP4 PRA and its potential role in the control of pain and
      inflammation associated with OA in dogs and cats.

PMID- 29067177
TI  - Seroprevalence of Schmallenberg virus infection in sheep and goats flocks in
      Germany, 2012-2013.
AB  - Schmallenberg virus (SBV) is a member of the family Bunyaviridae and mainly
      affects ruminants. It is transmitted by biting midges, first and foremost
      Culicoides spp., and causes congenital malformations reflected in arthrogryposis
      hydranencephaly (AH) syndrome. The aim of this study was to collect data on the
      emergence of SBV as a new arthropod-borne disease introduced into Europe in 2011.
      Germany was located in the core region of the 2011/2012 epidemic. Following two
      seroprevalence studies in the north-west of Germany in 2012, this study focused
      on the epidemiology and distribution of SBV throughout 130 small ruminant flocks
      in the whole country. Blood samples were obtained of 30 animals per flock and a
      SBV-specific questionnaire was used to collect operating data of the farms. The
      median within-herd seroprevalence for all 130 flocks tested was 53.3% with a
      total range from 0% to 100%. The median within-herd seroprevalence for goats was
      30% [interquartile range (IQR): 40.3%] and 57% for sheep (IQR: 43.3%). Small
      ruminant flocks kept permanently indoors or housed overnight had a significantly
      lower seroprevalence than flocks kept permanently outdoors. In addition, this
      study revealed a significantly lower seroprevalence in the north-east of Germany.
      These results show that small ruminants in Germany are still at risk of
      contracting new SBV infections following incomplete seroconversion of flocks
      especially in the north-east of Germany. This might contribute to SBV becoming
      enzootic in central and northern Europe. Furthermore, the survey revealed that
      housing animals at least during mating and early pregnancy may reduce the risk of
      new SBV infections and may thus be an option to reduce losses as long as there is
      no licensed vaccine available on the German market.

PMID- 29067178
TI  - Assessment of practices, capacities and incentives of poultry chain actors in
      implementation of highly pathogenic avian influenza mitigation measures in Ghana.
AB  - The animal health services-seeking behaviour of animal owners related to
      prevention and control of animal diseases may influence their decisions as to
      whether or not to use services provided by the public or private sectors. The
      specific objective of this paper was to assess the practices, capacities and
      incentives of actors involved in highly pathogenic avian influenza (HPAI) control
      to provide information for prevention and control in Ghana. Questionnaires were
      designed based on specific practices, incentives and capacities associated with
      each mitigation measure that was being assessed. Two peacetime preventive
      mitigation measures (biosecurity and reporting) and two outbreak containment
      measures (culling with compensation and movement control) were selected for
      evaluation. Supply chain actors were characterised based on baseline information.
      Tables were generated showing proportions of respondents in the various response
      categories in Likert-scale type itemised questionnaire. Mean scores (and their
      standard deviations) for the various actors with regard to mitigation measures
      were calculated. Pair-wise comparisons were done using t-ratio statistic and
      significance of differences were determined at a Bonferroni adjusted P-value of
      0.0024. The study found statistically significant differences between certain
      actors for practices (biosecurity, reporting, culling and compensation and
      movement controls), incentives (reporting and movement control) and capacities
      (reporting and movement control). The findings provide lessons to help improve
      education and messages on HPAI and to help provide technical assistance targeted
      at specific actors to prevent and control future HPAI H5N1 outbreaks in Ghana.

PMID- 29067179
TI  - Evaluation of the kinetics of anti-NP and anti-HA antibody after infection of
      Pekin ducks with low pathogenic avian influenza virus.
AB  - Serological monitoring is a feature of surveillance programmes for the detection
      of the circulation of notifiable low pathogenic avian influenza (LPAI) viruses in
      commercial poultry holdings. Commercial multispecies nucleoprotein (NP) enzyme
      linked immunosorbent assays (ELISAs) have been replacing the haemagglutination
      inhibition (HI) test as pre-screening tools. Few comparative studies have been
      conducted to test sera from domestic ducks for diagnostic purposes. Therefore, we
      evaluated the correlation between commercial NP ELISAs and the HI test. Anti-NP
      and anti-haemagglutinin (HA) antibodies were measured in sera from domestic ducks
      that had undergone serological screening and from juvenile domestic Pekin ducks
      that were experimentally infected with LPAI viruses. The findings highlight an
      absence of a correlation between NP ELISA and HI results with both field and
      experimental duck sera. Dissimilar kinetics of the antibodies detected during the
      follow-up evaluation of the humoral immune responses in experimentally infected
      ducks may explain this lack of correlation. Indeed, anti-NP titres decreased over
      time, whereas anti-HA titres remained unchanged after inoculation with the H3N1
      LPAI virus isolated from domestic duck or the H7N1 LPAI virus isolated from
      chicken. Despite these differences, the NP ELISA may serve as a valid pre
      screening tool to detect circulating LPAI viruses in domestic duck populations at
      the flock level.

PMID- 29067180
TI  - Pilot study on the effect of subcutaneous administration of lactated Ringer's
      solution on biochemistry parameters in healthy euvolemic cats.
AB  - Subcutaneous fluid administration is a commonly used therapy in veterinary
      practice. Its safety and efficacy have been demonstrated in human clinical
      studies, but have only rarely been discussed in the veterinary literature. This
      prospective observational study was performed to evaluate changes during a 24 h
      period in serum biochemistries associated with administration of lactated
      Ringer's solution subcutaneously to healthy cats. Lactated Ringer's solution was
      administered subcutaneously once to ten healthy, euvolemic cats at a dose of 22
      mL kg-1. Blood biochemistry analytes were sampled at baseline and at serial time
      points for a total of 24 h. Changes in biochemical analytes at each time point
      were compared to baseline and evaluated for statistical significance. Serum blood
      urea nitrogen (BUN) was significantly less than baseline at 4, 6, 12, 18, and 24
      h post-infusion. Serum creatinine was significantly less than baseline at 2, 4
      and 6 h. Packed cell volume (PCV) was significantly less than baseline at 6, 12,
      18, and 24 h. Total plasma proteins were significantly less than baseline at all
      time points. Serum electrolytes did not change from baseline at any time point.
      Urine specific gravity was significantly increased from baseline only at 6 h post
      Lactated Ringer's solution (LRS) administration. Subcutaneous administration of
      lactated Ringer's solution appears to result in haemodilution with minimal change
      to serum electrolyte concentrations in clinically normal, euvolemic cats.

PMID- 29067181
TI  - Differing perceptions - Swedish farmers' views of infectious disease control.
AB  - Although farm biosecurity reduces the risk of disease spread among livestock,
      this knowledge is not always applied. Farmers' application of disease preventive
      measures is expected to depend on many things, e.g. whether they consider disease
      prevention possible and demographic factors. In this study, Swedish livestock
      farmers' perspectives on occurrence, control and communication related to
      infectious livestock diseases were investigated. A questionnaire study was
      performed in 2012-2013, and included responses from almost 2000 livestock farmers
      with cattle, pigs, sheep or goats. Associations between responses and factors
      related to herd type and demography were investigated using multivariable
      regression models. Results showed a strong general agreement among farmers that
      disease prevention is important. However, results also showed differing opinions
      among farmers. For example, female farmers indicated higher levels of perceived
      knowledge of disease spread and a stronger belief that they can prevent disease
      introduction. Results indicate that farmers who believe they have the necessary
      knowledge, have stronger sense of control and also demand that others take
      responsibility to prevent spread. Furthermore, dairy farmers were more likely to
      respond that repeated exposure to infections could be beneficial for animal
      health. The number of perceived disease outbreaks was also higher among these
      farmers. Regarding government issued compensation to farmers in case of
      outbreaks, a wide range of opinions were recorded. Responses confirm that the
      farm veterinarian is an important source of disease information and several
      different communication channels are needed to reach farmers. In conclusion, our
      results show that factors such as gender, education level and age influence how
      prevention and occurrence of disease outbreaks are perceived and best
      communicated. We suggest that efforts are made to increase knowledge about
      disease prevention among farmers and veterinary practitioners and that farm
      veterinarians should be encouraged to motivate farmers to strengthen farm
      biosecurity.

PMID- 29067183
TI  - Atopic dermatitis and the intestinal microbiota in humans and dogs.
AB  - The prevalence of human and canine allergic diseases is commonly perceived to be
      increasing. Suggested predisposing factors in people and dogs include increased
      allergen load, increased exposure to pollutants, reduced family size, reduced
      microbial load and less exposure to infection at a young age, increasingly
      urbanised environment, and changes in dietary habits. Genetic make-up may provide
      a template for phenotypic predisposition which is strongly influenced by our diet
      and environment leading to constant regulation of gene expression. One way in
      which diet can alter gene expression is via its effects on the gut flora or
      microbiota, the collection of microbes residing in the gastrointestinal tract.
      The resident microbiota is important in maintaining structural and functional
      integrity of the gut and in immune system regulation. It is an important driver
      of host immunity, helps protect against invading enteropathogens, and provides
      nutritional benefits to the host. Disruption of the microbiota (dysbiosis) may
      lead to severe health problems, both in the gastrointestinal tract and extra
      intestinal organ systems. The precise mechanisms by which the intestinal
      microbiota exerts its effects are only beginning to be unravelled but research is
      demonstrating close links between gut microflora and many factors involved in the
      pathogenesis of atopic dermatitis (AD). AD and indeed any other 'skin disease',
      may be seen as a possible manifestation of a more systemic problem involving gut
      dysbiosis and increased intestinal permeability, which may occur even in the
      absence of gastrointestinal signs. Manipulation of the canine intestinal
      microbiota as a method for modifying atopy, may be attempted in many ways
      including avoidance of certain foods, supplementation with probiotics and
      prebiotics, optimising nutrient intake, minimising stress, antimicrobial therapy,
      correction and prevention of low stomach acid, and faecal microbiota
      transplantation (FMT).

PMID- 29067182
TI  - Understanding the canine intestinal microbiota and its modification by pro-, pre-
      and synbiotics - what is the evidence?
AB  - Interest in the composition of the intestinal microbiota and possibilities of its
      therapeutic modifications has soared over the last decade and more detailed
      knowledge specific to the canine microbiota at different mucosal sites including
      the gut is available. Probiotics, prebiotics or their combination (synbiotics)
      are a way of modifying the intestinal microbiota and exert effects on the host
      immune response. Probiotics are proposed to exert their beneficial effects
      through various pathways, for example production of antimicrobial peptides,
      enhancing growth of favourable endogenous microorganisms, competition for
      epithelial colonisation sites and immune-modulatory functions. Despite widespread
      use of pro-, pre- and synbiotics, scientific evidence of their beneficial effects
      in different conditions of the dog is scarce. Specific effects of different
      strains, their combination or their potential side-effects have not been
      evaluated sufficiently. In some instances, in vitro results have been promising,
      but could not be transferred consistently into in vivo situations. Specific
      canine gastrointestinal (GI) diseases or conditions where probiotics would be
      beneficial, their most appropriate dosage and application have not been assessed
      extensively. This review summarises the current knowledge of the intestinal
      microbiome composition in the dog and evaluates the evidence for probiotic use in
      canine GI diseases to date. It wishes to provide veterinarians with evidence
      based information on when and why these products could be useful in preventing or
      treating canine GI conditions. It also outlines knowledge about safety and
      approval of commercial probiotic products, and the potential use of faecal
      microbial transplantation, as they are related to the topic of probiotic usage.

PMID- 29067185
TI  - Vitamin E supplementation fails to impact measures of oxidative stress or the
      anaemia of feline chronic kidney disease: a randomised, double-blinded placebo
      control study.
AB  - This study was designed to test the hypothesis that supplementation with vitamin
      E, an antioxidant, in cats with chronic kidney disease (CKD), would reduce
      oxidative stress and its impact on RBC membrane fragility, resulting in these
      cats maintaining a greater packed cell volume (PCV) compared with CKD cats not
      receiving supplementation. Thirty-six cats with CKD were randomly assigned to
      receive either daily vitamin E or a placebo for 3 months in a double-blinded
      study design. History and physical examination, blood pressure, complete blood
      count (CBC), PCV, biochemical profile and urinalysis (UA) were determined.
      Parameters of oxidative stress and osmotic fragility were measured. Cats were
      administered vitamin E or placebo once daily for 3 months. Cats were then
      reassessed and the diagnostics were repeated. Twenty-four cats completed the
      study, 11 in the vitamin E group and 13 in the placebo group. There were no
      significant differences between the two groups at the start, or upon completion
      of the study with regard to biochemical parameters, oxidative stress, erythrocyte
      osmotic fragility or PCV. None of these parameters changed significantly in
      either group over the treatment period. Daily supplementation with 30 IU of
      vitamin E did not affect the measures of oxidative stress or the anaemia seen in
      cats with CKD.

PMID- 29067184
TI  - A survey of pet feeding practices of dog owners visiting a veterinary practice in
      Colombo, Sri Lanka.
AB  - In Sri Lanka, home-cooked diets are often fed due to the cost and poor
      availability of commercial diets. Milk has traditionally been a popular food to
      give to dogs in this country. There is a recent perceived increase in the number
      of owners choosing commercial diets for their pets. This study aimed to determine
      how dog owners visiting a single veterinary practice in Colombo fed their pets.
      We hoped that this would help achieve a general understanding of pet feeding
      practices in Sri Lanka and gain some basic demographic information on the owned
      dog population. The study was conducted via questionnaires distributed to pet
      owners visiting a first opinion and referral practice in Colombo. Hundred
      questionnaires were collected and analysed, 69% of study dogs were neutered, 42%
      of dogs were fed only home-cooked food, while 18% were fed only commercial food.
      About 40% of dogs were fed a mixture of commercial and home-cooked food, 49% of
      dogs were fed milk as a separate meal in addition to their normal diet and 57% of
      dogs received dietary supplements. Dogs consuming commercial food for more than
      half their intake were no less likely (P = 0.75) to receive dietary supplements
      than dogs fed homemade food for more than half their diet. This study provides
      some basic information regarding the feeding practices and demographics of the
      owned dog population in one Sri Lankan city, Colombo, highlighting some areas of
      concern.

PMID- 29067186
TI  - Treatment of canine meningoencephalomyelitis of unknown aetiology with
      mycophenolate mofetil and corticosteroids: 25 cases (2007-2012).
AB  - The use of mycophenolate mofetil (MMF) for a variety of immune-mediated diseases
      in veterinary medicine has been described. However, there is only a small number
      of cases documenting its use in dogs with meningoencephalomyelitis of unknown
      aetiology (MUE). We hypothesized that the use of MMF and corticosteroids in dogs
      with MUE results in comparable survival data to other published treatment
      protocols and is associated with limited adverse effects. A retrospective study
      of medical case records of dogs clinically diagnosed with MUE recorded
      signalment, neuroanatomic localization, magnetic resonance imaging findings,
      cerebrospinal fluid analysis results, medications administered, follow-up
      neurologic examinations, survival and adverse events. Variables were compared
      between dogs which were treated with MMF within 30 days of diagnosis (immediate
      group) vs. dogs in which MMF therapy was started >30 days after diagnosis
      (delayed group). Twenty-five cases of MUE were identified. The overall median
      survival time from diagnosis was 731 days (range 43-1672 days). After 1 month of
      MMF treatment, 92% of dogs showed improvement on a neurological examination.
      There was no significant effect of any recorded parameter on survival, including
      delayed vs. immediate initiation of MMF treatment. Dogs with delayed treatment
      had significantly lower clinical remission rates than dogs with immediate
      treatment at 6 months after starting MMF. Adverse events were identified in two
      cases (8%) and were characterized by mild gastrointestinal signs (vomiting and
      decreased appetite). Administration of MMF appears safe in dogs with MUE. The use
      of MMF results in comparable survival times to alternate immunosuppressive
      protocols.

PMID- 29067187
TI  - Phylogenetic analysis of Dermatophilus congolensis isolated from naturally
      infected cattle in Abeokuta and Ilorin, Nigeria.
AB  - Dermatophilus congolensis, the aetiological agent of dermatophilosis, is a
      pleomorphic, Gram-positive actinomycete, which infects animals and humans. Often,
      there is a wrong diagnosis of the infection in animals because of the close
      resemblance of the organism with other members of the family Actinomycetaceae. In
      this study, molecular tools were applied to suspected isolates of D. congolensis
      obtained from naturally infected cattle in Nigeria for confirmation of
      dermatophilosis. DNA extraction from 54 suspected pure colonies of D. congolensis
      was carried out using the QIAamp(r) DNA Mini extraction kit. PCR targeted at the
      16S rRNA gene was employed for the confirmation of D. congolensis using 5'
      ACATGCAAGTCGAACGATGA-3' and 5'-ACGCTCGCACCCTACGTATT-3' as forward and reverse
      primers, respectively. Positive amplicons were then sequenced directly using Big
      Dye Terminator Cycle Sequencing Kit with the forward primers and AmpliTaq-FS DNA
      Polymerase. Nucleotide sequences were aligned using bioedit (Ibis Biosciences
      Carlsbad, CA USA) and the phylogenetic analysis was carried out using mega 5.2
      (Center for Evolutionary Medicine and Informatics, The Biodesign Institute,
      Tempe, Arizona, USA) software programme. The aligned nucleotide sequences of 10
      positive D. congolensis isolates had between 94% to 99% homology with the
      sequences of D. congolensis satellite DNA in GenBank. This result also revealed
      that the sequenced D. congolensis are of different strains. Phylogenetic analysis
      revealed that D. congolensis, though closely related to Nocardia brasiliensis (NR
      074743.01) and Streptomyces sp. (JN 400114.1), belongs to different genus. In
      conclusion, molecular tools employed in the study were able to confirm the
      identity of the test organisms as D. congolensis. It can also be concluded that
      two strains of D. congolensis obtained from the study can still be accommodated
      within the previously listed strains available in GenBank while the remaining
      eight may be different strains of D. congolensis not yet listed in GenBank.

PMID- 29067188
TI  - Erratum: Vitamin D status in cats with feline immunodeficiency virus.
AB  - [This corrects the article DOI: 10.1002/vms3.11.].

PMID- 29067189
TI  - Evaluation of carboplatin sustained-release delivery system in dogs with cancer.
AB  - The objective of the study was to assess the carboplatin sustained-release (CSR)
      as an injectable, biodegradable polymer system designed to uniformly release
      carboplatin over 30 days at a dose of 350 mg m-2. The study involved seven client
      owned dogs with histologically or cytologically confirmed neoplasia that were
      treated with CSR intramuscularly. Platinum levels were measured at days 0, 7, 14,
      21 and 28. Complete blood cell (CBC) counts, body weight, local toxicity and side
      effects were also evaluated at the time of platinum measurement at days 0, 7, 14,
      21 and 28. CSR released carboplatin steadily over 30 days. Neutropenia was noted
      as Grade 3 in one dog (14%) and Grade 4 in two dogs (29%) at day 14, and Grade 4
      in one dog (14%) at day 21. Thrombocytopenia was noted as Grade 2 in four dogs
      (57%), Grade 3 in one dog (14%) and Grade 4 in one dog (14%) at day 14; Grade 2
      in two dogs (29%) and Grade 3 in one dog (14%) at days 21 and 28. Grade 1
      lethargy in one dog (14%) and Grade 1 nausea in dog (14%) occurring within 7 days
      after administration. No obvious local injection site reactions were noted. CSR
      administered at 350 mg m-2 intramuscularly resulted in a steady release over 30
      days. Myelosuppression (Grade 4) was noted in 86% of patients. CSR released the
      drug slowly and steadily, however additional studies are needed to assess
      acceptable dosage requirements.

PMID- 29067190
TI  - Molecular prevalence of Toxoplasma gondii DNA in goats' milk and seroprevalence
      in Northwest Tunisia.
AB  - Toxoplasmosis is a worldwide zoonosis with high impact on human and animal
      health. Consumption of unpasteurized milk is a risk factor of human
      toxoplasmosis. The aim of this study was to estimate the seroprevalence and
      molecular prevalence of T. gondii in goats' milk in Northwest of Tunisia
      (Jendouba Governorate). A total number of 77 blood samples were collected from
      six herds were screened with a commercial ELISA kit for T. gondii antibodies. For
      the same goats' samples, a nested PCR was performed to detect T. gondii DNA in
      milk. The seroprevalence of T. gondii infection was 31.2% (+/-0.05) while the
      molecular prevalence of this parasite in milk was estimated to 7.8% (+/-0.03). A
      very low value of kappa showed that there is not agreement between seroprevalence
      and parasite prevalence in milk. These results suggest that the consumption of
      raw milk from naturally infected goats is a potential source of human infection.
      An extension programme should be implemented to decrease related to goats' raw
      milk consumption.

PMID- 29067191
TI  - Awareness of rabies and response to dog bites in a Bangladesh community.
AB  - Community awareness regarding rabies and treatment seeking behaviours are
      critical both for the prevention and control of the disease in human and animals.
      We conducted a study to explore people's awareness about rabies, their attitudes
      towards dogs and practices associated with treating dog bites in Satkhira Sadar,
      a south-western sub-district of Bangladesh. Of the total 3200 households (HHs)
      surveyed, the majority of the respondents have heard about rabies (73%) and there
      was a high level of awareness that dog bite is the main cause of rabies (86%),
      and that rabies can be prevented by vaccination (85%). However, 59% of the dog
      bite victims first seek treatment from traditional healers instead of visiting
      the hospitals, 29% received the rabies vaccine, 2% practiced proper wound washing
      with soap and water, while 4.8% have not taken any measures. None of the victims
      have received rabies immunoglobulin (RIG). Of the respondents, 5.2% reported a
      history of dog bite in at least one family member, and 11.8% reported a history
      of dog bite in domestic animals during the previous year. The HHs having a higher
      number of family members (OR: 1.13, 95% CI: 1.07-1.2), having a pet dog (OR: 2.1,
      95% CI: 1.4-3.2) and caring or feeding a community dog (OR: 2.1, 95% CI: 1.4-2.9)
      showed an increased risk of getting a dog bite. Among the bite victims, 3.6% (n =
      6) humans and 15.8% (n = 60) animals died. As a measure for dog population
      management (DPM), 56% preferred sterilization while the rest preferred killing of
      dogs. The current treatment seeking behaviours of the respondents should be
      improved through additional education and awareness programme and better
      availability for the provision of post-exposure prophylaxis in Bangladesh. We
      recommend scaling up national mass dog vaccination and DPM to reduce the burden
      of rabies cases and dog bites in Bangladesh.

PMID- 29067192
TI  - Comparative efficacy of tulathromycin and tildipirosin for the treatment of
      experimental Mycoplasma bovis infection in calves.
AB  - The objective of this negative controlled, blinded, randomised, parallel group
      study was to compare the efficacy of two injectable macrolide antimicrobials,
      tulathromycin and tildipirosin, administered by single subcutaneous injection at
      dose rates of 2.5 and 4.0 mg kg-1 bodyweight, respectively, in the treatment of
      an experimentally induced Mycoplasma bovis infection in calves. A total of 238 M.
      bovis-negative calves were challenged on three consecutive days with M. bovis by
      endobronchial deposition. Post-challenge, a total of 126 animals fulfilled the
      inclusion criteria and were randomly allocated to three treatment groups:
      tulathromycin, tildipirosin and saline. Clinical observations for signs of
      respiratory disease and injection site assessments were conducted daily for 14
      days post-treatment. The animals were then killed, the lungs were examined for
      evidence of lesions, and samples collected for bacterial isolation. Calves
      treated with tulathromycin had a lower percentage of lung with lesions (P =
      0.0079), lower mortality (P = 0.0477), fewer days with depressed demeanour (P =
      0.0486) and higher body weight (P = 0.0112) than calves administered
      tildipirosin.

PMID- 29067193
TI  - A phase I clinical study to evaluate safety of orally administered, genetically
      engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma.
AB  - We conducted a prospective phase I study to evaluate safety of an orally
      administered Salmonella encoding IL-2 (SalpIL2) in combination with amputation
      and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was
      assessed as a secondary measure. The first dose of SalpIL2 was administered to 19
      dogs on Day 0; amputation was done after 10 days with chemotherapy following 2
      weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total
      of five doses of doxorubicin and six doses of SalpIL2. There were six reportable
      events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving
      SalpIL2 had significantly longer disease-free interval (DFI) than a comparison
      group of dogs treated with doxorubicin alone. Dogs treated using lower doses of
      SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The
      data indicate that SalpIL2 is safe and well tolerated, which supports additional
      testing to establish the potential for SalpIL2 as a novel form of adjuvant
      therapy for dogs with osteosarcoma.

PMID- 29067194
TI  - Neutering of German Shepherd Dogs: associated joint disorders, cancers and
      urinary incontinence.
AB  - German Shepherd Dogs are important in police and military work, and are a popular
      family pet. The debilitating joint disorders of hip dysplasia, cranial cruciate
      ligament tear (CCL) and elbow dysplasia can shorten a dog's useful working life
      and impact its role as a family member. For this study, veterinary hospital
      records were examined over a 14.5-year period on 1170 intact and neutered
      (including spaying) German Shepherd Dogs for joint disorders and cancers
      previously associated with neutering. The diseases were followed through 8 years
      of age, with the exception of mammary cancer (MC) in females that was followed
      through 11 years. The cancers followed, apart from mammary, were osteosarcoma,
      lymphoma, hemangiosarcoma and mast cell tumour. In intact males, 7% were
      diagnosed with one or more joint disorders, while in males neutered prior to a
      year of age, a significantly higher 21% were diagnosed with one or more joint
      disorders. In intact females, 5% were diagnosed with one or more joint disorders,
      while in females neutered prior to a year of age, this measure was significantly
      increased to 16%. The increased joint disorder incidence mostly associated with
      early neutering was CCL. MC was diagnosed in 4% of intact females compared with
      less than 1% in females neutered before 1 year. The occurrence of the other
      cancers followed through 8 years of age was not higher in the neutered than in
      the intact dogs. Urinary incontinence, not diagnosed in intact females, was
      diagnosed in 7% of females neutered before 1 year, a significant difference.
      These findings, profiling the increase in joint disorders associated with early
      neutering, should help guide the timing of neutering for this breed.

PMID- 29067195
TI  - Sternal bone marrow derived equine multipotent mesenchymal stromal cells (MSCs):
      investigations considering the sampling site and the use of different culture
      media.
AB  - Aspiration of equine sternal bone marrow is required for the cultivation of bone
      marrow-derived multipotent mesenchymal stromal cells (BM-MSCs) for regenerative
      therapies. For bone marrow aspiration as well as for MSC cultivation, there is a
      need to optimize techniques and protocols to enhance MSC harvest at minimized
      culture times. In a comparative study bone marrow aspirates from sternebra 4 and
      5 were collected at two different positions within the sternebrae, either from 10
      mm or from 30 mm dorsal from the ventral margin of the sternebrae. Accuracy of
      the puncture depth was confirmed by ultrasonography and computed tomography.
      Isolated MSCs were cultivated using media supplemented with three alternative
      sera, i.e. fetal calf serum, standardized horse serum and autologous serum. Due
      to morphological characteristics (spherical shape, only thin layer of hyaline
      cartilage at the ventral site, reliable bone marrow aspiration from only 10 mm
      intraosseous depth), sternebra 5 appeared most suitable for bone marrow
      aspiration. Cultivation and expansion of BM-MSCs was most efficient using fetal
      calf serum.

PMID- 29067196
TI  - Assessment of the sensitivity and specificity of serological (IFAT) and molecular
      (direct-PCR) techniques for diagnosis of leishmaniasis in lagomorphs using a
      Bayesian approach.
AB  - Leishmaniasis, caused by Leishmania infantum, is a vector-borne zoonotic disease
      that is endemic to the Mediterranean basin. The potential of rabbits and hares to
      serve as competent reservoirs for the disease has recently been demonstrated,
      although assessment of the importance of their role on disease dynamics is
      hampered by the absence of quantitative knowledge on the accuracy of diagnostic
      techniques in these species. A Bayesian latent-class model was used here to
      estimate the sensitivity and specificity of the Immuno-fluorescence antibody test
      (IFAT) in serum and a Leishmania-nested PCR (Ln-PCR) in skin for samples
      collected from 217 rabbits and 70 hares from two different populations in the
      region of Madrid, Spain. A two-population model, assuming conditional
      independence between test results and incorporating prior information on the
      performance of the tests in other animal species obtained from the literature,
      was used. Two alternative cut-off values were assumed for the interpretation of
      the IFAT results: 1/50 for conservative and 1/25 for sensitive interpretation.
      Results suggest that sensitivity and specificity of the IFAT were around 70-80%,
      whereas the Ln-PCR was highly specific (96%) but had a limited sensitivity (28.9%
      applying the conservative interpretation and 21.3% with the sensitive one).
      Prevalence was higher in the rabbit population (50.5% and 72.6%, for the
      conservative and sensitive interpretation, respectively) than in hares (6.7% and
      13.2%). Our results demonstrate that the IFAT may be a useful screening tool for
      diagnosis of leishmaniasis in rabbits and hares. These results will help to
      design and implement surveillance programmes in wild species, with the ultimate
      objective of early detecting and preventing incursions of the disease into
      domestic and human populations.

PMID- 29067197
TI  - Chemical immobilisation of dhole (Cuon alpinus), Indian jackal (Canis aureus
      indicus) and Indian wolf (Canis lupus pallipes) with ketamine hydrochloride
      xylazine hydrochloride.
AB  - Maintaining wild animals in captivity often requires chemical immobilisation to
      achieve various diagnostic, surgical and management interventions. Four dholes,
      two Indian grey wolves and four Indian jackals were immobilised using ketamine
      xylazine combination for either medical or management interventions. Based on the
      estimated body weight, canids were darted upon with 6-8 mg kg-1 ketamine and 0.7
      1.14 mg kg-1 xylazine. Initial signs of drug effect included decreased mentation
      and progressive ataxia followed by recumbency. The mean +/- SD of induction time
      was 14.25 +/- 2.75 (range: 11-17 min), 11 +/- 3.16 (range: 8-15 min) and 15.5 +/-
      3.54 (range: 13-18 min) in dhole, Indian jackal and Indian wolf, respectively.
      Hyperthermia was initially observed in all the jackals and dholes, whereas rectal
      temperature in wolves remained well within the normal range for canids. The mean
      duration of anaesthesia was 31 +/- 8.83 (range: 23-43 min), 32.5 +/- 5.32 (range:
      26-39 min) and 30.5 +/- 7.78 (range: 25-36 min) in dhole, Indian jackal and
      Indian wolf, respectively, with subsequent smooth and uneventful recovery in all
      the cases. The observations made during immobilisation procedures in this work
      suggest that chemical immobilisation of captive dhole, Indian wolf and Indian
      jackal with 6-8 mg kg-1 ketamine and 1 mg kg-1 xylazine is effective and safe for
      routine management and medical interventions in these species provided body
      temperature is closely monitored and corrected as appropriate.

PMID- 29067198
TI  - An extended release local anaesthetic: potential for future use in veterinary
      surgical patients?
AB  - One of the most effective means of preventing the transduction and transmission
      of acute and perioperative pain is through the use of local anaesthetics.
      However, local anaesthetics currently available have a relatively short duration
      of action. Although there are several tools available to treat perioperative pain
      in companion animals, overall, there is an unmet need for products that can be
      administered in the clinic, and provide pain relief for the crucial first few
      days following surgery in the home environment. Specifically, in relation to
      local anaesthetics, there is a clear unmet need for a long-acting local
      anaesthetic that can be added to the multimodal analgesic protocol to provide
      pain relief to patients in the home environment or during extended
      hospitalization. Bupivacaine liposomal injectable suspension recently became
      available for use in humans, and has proven efficacious and safe. This paper will
      review the use of local anaesthetics, particularly bupivacaine, in dogs and cats,
      and introduce a new formulation of prolonged release bupivacaine that is in
      development for dogs and cats.

PMID- 29067199
TI  - Antibiotic resistance in conjunctival and enteric bacterial flora in raptors
      housed in a zoological garden.
AB  - Antimicrobial resistance (AMR) in a wide range of infectious agents is a growing
      public health threat. Birds of prey are considered indicators of the presence of
      AMR bacteria in their ecosystem because of their predatory behaviour. Only few
      data are reported in the literature on AMR strains isolated from animals housed
      in zoos and none about AMR in raptors housed in zoological gardens. This study
      investigated the antibiotic sensitivity profile of the isolates obtained from the
      conjunctival and cloacal bacterial flora of 14 healthy birds of prey, 6
      Accipitriformes, 3 Falconiformes and 5 Strigiformes, housed in an Italian
      zoological garden. Staphylococcus spp. was isolated from 50% of the conjunctival
      swabs, with S. xylosus as the most common species. From cloacal swabs,
      Escherichia coli was cultured from all animals, while Klebsiella spp. and Proteus
      spp. were isolated from a smaller number of birds. Worthy of note is the
      isolation of Escherichia fergusonii and Serratia odorifera, rarely isolated from
      raptors. Staphylococci were also isolated. All the isolates were multidrug
      resistant (MDR). To the author's knowledge, this is the first report regarding
      the presence of MDR strains within raptors housed in a zoological garden. Since
      resistance genes can be transferred to other pathogenic bacteria, this represents
      a potential hazard for the emergence of new MDR pathogens. In conclusion, the
      obtained data could be useful for ex-situ conservation programmes aimed to
      preserve the health of the endangered species housed in a zoo.

PMID- 29067200
TI  - The risk of carriage of Salmonella spp. and Listeria monocytogenes in food
      animals in dynamic populations.
AB  - Salmonella spp. and Listeria monocytogenes are foodborne pathogens of global
      importance. We assessed their risks and associated factors in a highly dynamic
      population of animals. Animal and environmental samples were collected from dairy
      cattle, sheep, camel and chickens at either the farms or the abattoirs. The
      pathogens were detected using a combination of bacterial enrichment culture and
      real-time polymerase chain reaction (PCR). Data on putative risk factors were
      collect and analysed for their significance of association with these pathogens.
      Salmonella spp. were detected at higher proportions in sheep faeces and sheep
      carcasses in comparison to cattle faeces (odds ratio = 2.4 and 2.2,
      respectively). This pathogen was less common in milk or carcasses samples from
      cattle or chickens. Sheep and camel carcass samples were highly contaminated with
      Salmonella spp. Faecal samples from cattle had the most diverse serovars of
      Salmonella enterica including S. Newport, S. Haifa, S. Kedougou, S. Kentucky, S.
      Mbandaka and S. Goettingen. Exotic serovars in sheep included S. Eastbourne, S.
      Chester and S. Kottnus. Serovars that were shed in camel faeces included S.
      Newport, S. Bovismorbificans and S. Infantis. In all sampled populations,
      detection of Salmonella spp. was more likely during warmer months than cold
      months. Listeria monocytogenes was not common in the targeted populations and was
      detected at a rate of 2.4%, mainly from sheep carcasses. The study highlights the
      role of food animals as reservoirs of pathogens across boundaries since all feed
      are imported in that population from different parts of the world.

PMID- 29067201
TI  - An imaging investigation of in situ uroliths in hospitalized cats in New Zealand
      and in the United States.
AB  - The submission rates of feline uroliths to laboratories and the composition of
      uroliths have been reported in studies. The prevalence of uroliths reported on
      imaging findings has not been published. The objective of this retrospective
      study was to use imaging data to investigate the anatomical location and the
      prevalence of macroscopic in situ uroliths in cats. Radiographs, sonograms and
      imaging reports from two cohorts of cats (from New Zealand (n = 497) and the
      United States (n = 693)) from 2004-2013 were reviewed for the presence of in situ
      uroliths. Uroliths were categorized by their location in the lower or upper
      urinary tract. Radiographic studies were performed on 43% (212/497) of the cats
      from New Zealand and 50% (349/693) of the cats from the USA. Sonographic studies
      were performed on 57% (285/497) of the cats from New Zealand and 50% (344/693) of
      the cats from the USA. The total prevalence of uroliths was 3% in the New Zealand
      cohort and 13% in the USA cohort. Lower tract urolith prevalence in the New
      Zealand cohort was 2.4% (5/212) in cats <= 6y and 1.1% (3/285) in cats >6y. Upper
      tract urolith prevalence in the New Zealand cohort was 0.5% (1/212) in cats <= 6y
      and 1.8% (5/285) in cats >6y. Lower tract urolith prevalence in the United States
      cohort was 6.0% (11/183) in cats <= 6y and 2.9% (15/510) in cats >6y. Upper tract
      urolith prevalence in the United States cohort was 2.7% (5/183) in cats <= 6y and
      10.2% (52/510) in cats >6y. The prevalence of uroliths in the upper tract or
      lower tract was low in the New Zealand cohort compared to that of cats in the USA
      cohort, irrespective of age category. Geographical location may be important when
      evaluating risk factors for feline urolithiasis.

PMID- 29067202
TI  - Tolerability of a rapid-escalation vinblastine-prednisolone protocol in dogs with
      mast cell tumours.
AB  - Optimal chemotherapy protocols for high-risk mast cell tumours (MCTs) are
      unknown. The purpose of this study was to determine the tolerability and toxicity
      profile of a rapidly escalating vinblastine and prednisolone protocol (VPP) in
      which 3.00 mg/m2 was administered once 7 days apart: at day 14 and at day 21.
      Dogs with chemotherapy-naive MCTs presenting to the Oncology Service of a single
      institution were prospectively enrolled to receive escalating vinblastine, and
      haematology and a standardised quality-of-life questionnaire were assessed prior
      to each dosage. Thirty-four dogs were included: 30 with microscopic disease
      treated with adequate local therapy and four with macroscopic disease. Of 220
      doses of vinblastine administered, 4% were associated with grade 3 and 4
      toxicity. A total of 70% of dogs tolerated 3.00 mg/m2 given 7 days apart at day
      14 and 21, although 29% of dogs developed dose-limiting toxicities and 8%
      discontinued the protocol due to toxicity. In conclusion, VPP was well-tolerated
      overall, although prior to further dose intensity optimisation, it is important
      to determine if dose intensity is linked to outcome in canine MCT to avoid
      unwarranted toxicity.

PMID- 29067203
TI  - Prospective study evaluating the incidence of bacteraemia and bacteruria in
      afebrile and febrile neutropaenic dogs undergoing chemotherapy.
AB  - The purpose of this prospective study was to determine the incidence and
      character of bacteraemia and bacteruria in afebrile and febrile neutropaenic dogs
      undergoing cytotoxic chemotherapy. Fifty-five neutropaenic dogs presenting to the
      University of Wisconsin Veterinary Medical Teaching Hospital were enrolled for a
      total of 57 neutropaenic episodes. The overall incidence of bacteraemia was 12.3%
      (n = 7/57). Three afebrile dogs and four febrile dogs were bacteraemic; this
      difference was not significant (P = 0.6968). The overall incidence of bacteruria
      was 7.5% (n = 4/53). Two afebrile dogs and two febrile dogs were bacteruric; this
      difference was not significant (P = 1.0). Of the positive blood cultures, the
      majority of organisms cultured (n = 6/7) were gram-positive organisms with one
      gram-negative organism. Three of the positive blood cultures showed in vitro
      resistance to more than one antimicrobial agent. Clinical parameters (age, body
      weight, heart rate, rectal temperature, neutrophil count, haematocrit and
      platelet count) were not predictive of bacteraemia. The results of this study
      were not sufficient to justify the use of blood cultures as a first-line
      diagnostic test for neutropaenic patients. Blood cultures may have utility in
      individual case management for a minority of patients in guiding antibiotic
      choice in the case of resistant bacterial infections. Blood cultures may serve as
      a tool for antimicrobial de-escalation, although further study is needed.

PMID- 29067205
TI  - High frequency of seropositivity of Leptospira in cattle in North Tunisia.
AB  - The authors report a survey carried out in a cattle farm between January and
      April 2009 in Mateur region (Northern Tunisia). Seroprevalence by Microscopic
      Agglutination Test (MAT) was estimated to 81.4 +/- 6% and 35 +/- 2% in cows and
      calves, respectively. Seropositivity to more than one serovar was noticed in 91%
      (81/89) of infected animals. The examination of the distribution pattern of
      Leptospira serovars involved in this outbreak indicates that serovar Pomona was
      the predominant one (75.3%), followed by Autumnalis (59.5%), Bim (58.4%) and
      Munchen (55%). High titres (between 400 and 6400) were found in 68.7% of the
      tested animals and were correlated with clinical onset of leptospirosis.
      Leptospirosis is an underestimated pathogen in Tunisia; further investigations
      are needed to study the epidemiology both in man and animals and to implement
      effective control measures.

PMID- 29067204
TI  - Using oral fluids samples for indirect influenza A virus surveillance in farmed
      UK pigs.
AB  - Influenza A virus (IAV) is economically important in pig production and has broad
      public health implications. In Europe, active IAV surveillance includes
      demonstration of antigen in nasal swabs and/or demonstration of antibodies in
      serum (SER) samples; however, collecting appropriate numbers of individual pig
      samples can be costly and labour-intensive. The objective of this study was to
      compare the probability of detecting IAV antibody positive populations using SER
      versus oral fluid (OF) samples. Paired pen samples, one OF and 5-14 SER samples,
      were collected cross-sectional or longitudinally. A commercial nucleoprotein (NP)
      based blocking ELISA was used to test 244 OF and 1004 SER samples from 123 pens
      each containing 20-540 pigs located in 27 UK herds. Overall, the IAV antibody
      detection rate was higher in SER samples compared to OFs under the study
      conditions. Pig age had a significant effect on the probability of detecting
      positive pens. For 3-9-week-old pigs the probability of detecting IAV antibody
      positive samples in a pen with 95% confidence intervals was 40% (23-60) for OF
      and 61% (0.37-0.80) for SER (P = 0.04), for 10-14-week-old pigs it was 19% (8-40)
      for OF and 93% (0.71-0.99) for SER (P < 0.01), and for 18-20-week-old pigs it was
      67% (41-85) for OF and 81% (0.63-0.91) for SER (P = 0.05). Collecting more than
      one OF sample in pens with more than 25 less than 18-week-old pigs should be
      further investigated in the future to elucidate the suitability of OF for IAV
      surveillance in herds with large pen sizes.

PMID- 29067206
TI  - Molecular detection and phylogenetic analyses of Toxoplasma gondii from naturally
      infected sheep in Northern and Central Tunisia.
AB  - Toxoplasmosis is a worldwide zoonosis caused by the parasitic protozoan
      Toxoplasma gondii. It can infect all warm-blooded vertebrate species and causes
      abortions and birth defects in pregnant women and pregnant ewes. The objective of
      this study was to estimate the prevalence of infection with T. gondii in sheep
      meat in the region of Sidi Bouzid (central Tunisia) and Beja (northern Tunisia),
      the realization of a descriptive study of risk factors and the phylogenetic
      analyses of T. gondii. Neck muscle samples were obtained from 174 ewes and ewe
      lamb slaughtered in Sidi Bouzid and 150 lambs slaughtered in Beja. DNA was
      extracted from the samples using the Wizard(r) genomic DNA purification kit. A
      nested PCR using two pairs of primers (NN 1 and NN2, Tg-NP1 and Tg-NP2) were used
      to detect infection with T. gondii, which was then confirmed by sequencing. Eight
      T. gondii amplicons were sequenced (accession number KT896498) and deposited in
      GenBank. The T. gondii amplicons showed 97-100% identities with GenBank
      sequences. A phylogenetic tree was then constructed. The nested PCR detected T.
      gondii DNA in 31% of animals tested in Sidi Bouzid and 32% of lambs tested in
      Beja. No significant difference in the prevalence of T. gondii infection was
      established between the two tested regions. In both regions, no significant
      variation of the infection depending on age, breed and locality was found.

PMID- 29067207
TI  - Abdominal ultrasonography of the healthy howler monkey (Alouatta fusca).
AB  - Abdominal ultrasonography was performed in six healthy adult brown howler monkeys
      Alouatta fusca and the normal ultrasonographic anatomy of the liver, gallbladder,
      stomach and urinary tract described for the first time. Findings were compared
      with post-mortem studies. The renal cortex was isoechoic to the spleen and
      isoechoic or hyperechoic to the liver. Kidney length and renal arterial resistive
      index, systolic and diastolic velocity were calculated. The liver showed a
      homogeneous hypoechogenic echotexture. The aim of this study was to describe the
      normal abdominal viscera echoanatomy providing information of normal abdominal
      anatomical structures in the howler monkey.

PMID- 29067208
TI  - Serological survey of Leptospira interrogans, Toxoplasma gondii and Trypanosoma
      cruzi in free roaming domestic dogs and cats from a marginated rural area of
      Yucatan Mexico.
AB  - To evaluate the serological status for Trypanosoma cruzi, Toxoplasma gondii and
      Leptospira interrogans antibodies in free roaming dogs and cats from a marginated
      rural community in Yucatan Mexico, 100 households were visited and animals
      sampled. From the 106 samples, 93 were from dogs and 13 were from cats. Frequency
      of positive results for T. gondii, T. cruzi and Leptospira spp was 97.8%, 9.7%
      and 45.2% for dogs and 92.3%, 0.0% and 15.2% for cats, respectively. No
      associations with age, sex and body condition was found for T. gondii and
      Leptospira spp neither for the place where pets sleep, fumigation or presence of
      triatomes in the household in the case of T. cruzi. For leptospirosis the most
      common serovars found were Canicola, Autralis and Bratislava in dogs and cats
      with titres of 100 or 200 with exception of one dog with a titre of 400. The high
      frequency of seropositive dogs suggests a high circulation of the agents in the
      population of free roaming owned dogs and cats probably due to the lack of
      control of the reservoirs and vectors involved. Domestic animals in those rural
      communities can be sentinels to assess the risk of human exposure in the rural
      communities.

PMID- 29067209
TI  - Complementary and alternative medicine for the management of orthopaedic problems
      in Swiss Warmblood horses.
AB  - It appears that complementary and alternative medicine (CAM) is used increasingly
      often in horses for the assessment and treatment of suspected orthopaedic
      problems, especially back problems. The aim of this study was to determine the
      frequency of CAM use for the management of orthopaedic problems in a defined
      population of Swiss Warmblood horses. A total of 239 owners and caretakers of
      horses from a pre-defined database were called by a veterinarian to participate
      in the survey. A standardized questionnaire was designed to determine, for each
      orthopaedic case, where the localization of the problem was (limb or back) and if
      conventional medicine or CAM was used for consultation and treatment. When CAM
      was employed, the CAM discipline and administrator (veterinarian or alternative
      therapist) was defined. A total of 222 cases in 170 horses with orthopaedic
      problems were identified. Sixty-two horses were identified with a back problem,
      96 horses with a lameness involving one or more limbs and 12 horses with a
      combined back problem and lameness. CAM was used commonly in this population
      (73.9%, 164 of 222) for both diagnostic workup and treatment of suspected
      orthopaedic problems, but was rarely administered by a veterinarian (12%, 27 of
      222). In general, if a back problem was suspected by the owner, CAM was more
      frequently applied for diagnosis and treatment than in cases where a lameness was
      suspected; (91.9%, 68 of 74) vs. (64.9%, 96 of 148) (P < 0.001), respectively.
      Osteopathy was the most frequently applied CAM discipline. CAM was frequently
      used for diagnostic and therapeutic purposes in Swiss Warmblood horses with
      suspected orthopaedic problems. CAM practitioners were consulted predominantly if
      a back problem was suspected, and the majority of CAM practitioners were not
      veterinarians.

PMID- 29067211
TI  - Pilot assessment of vascular endothelial growth factor receptors and trafficking
      pathways in recurrent and metastatic canine subcutaneous mast cell tumours.
AB  - Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological
      behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2
      (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of
      this signalling pathway for disease pathobiology is not clear. The objective of
      this study was to quantify VEGF-A, VEGFR2, pVEGFR2, the VEGF co-receptor
      Neuropilin 1 (NRP-1) and the E3 ubiquitin protein ligase c-Cbl in canine scMCT,
      and to evaluate their association with disease outcome. Immunohistochemical
      staining for biomarkers was quantified from 14 cases of canine scMCT using manual
      and computer-assisted methods. Kaplan-Meier curves were generated for disease
      free survival (DFS) and compared using Mantel-Cox log-rank analysis. Cases with
      high levels of neoplastic cell VEGFR2, pVEGFR2 or c-CBL immunoreactivity had
      significantly reduced DFS. All cases displayed neoplastic cells positive for VEGF
      A, which was significantly associated with pVEGFR2 immunoreactivity. There were
      also significant positive correlations between VEGFR2 and pVEGFR2, and between c
      CBL and pVEGFR2 levels. This pilot study demonstrates the potential utility of
      these markers in a subset of scMCT in dogs.

PMID- 29067212
TI  - Awareness and mitigation measures on highly pathogenic avian influenza in
      pastoral poultry flocks of North-central Nigeria: any challenging gap?
AB  - Village poultry closely interact with wild birds and other livestock in
      extensively managed poultry flocks, a practice common in pastoral communities of
      Nigeria. This practice provides sustained dissemination of avian viruses, such as
      highly pathogenic avian influenza (HPAI) H5N1 virus. The objectives of this study
      were to assess their knowledge/awareness, risks identification and biosecurity
      measures on HPAI H5N1 in pastoral poultry flocks. A questionnaire-based cross
      sectional survey was conducted in systematically selected pastoral households of
      North-central Nigeria between May 2015 and June 2016. A total of 422 pastoralists
      participated in the study. Mean age of the respondents was 54.7 +/- 11.4 SD years
      and 36.0% of them were in age group 50-59 years. The majority (81.3%) of
      respondents were of the Fulani tribe. Also, 64.9% of the respondents had no
      formal education and only 6.9% had tertiary education. About 30.8% of the nomadic
      and 81.0% of sedentary pastoralists significantly mentioned avian influenza to be
      a zoonotic disease. Very few nomadic (10.9%) and sedentary (26.1%) pastoralists
      significantly reported restriction of birds' movement to nearby water bodies as
      biosecurity measure. Only 7.6% of the nomadic and 16.1% of sedentary pastoralists
      practiced keeping of birds according to species. Sedentary pastoralists were more
      likely to have significant knowledge about HPAI H5N1 than the nomadic (OR: 1.76;
      94% CI: 1.19-2.61). Female pastoralists were more likely to practice significant
      biosecurity measures against HPAI H5N1 than the males (OR: 1.99; 95% CI: 1.28
      3.09). The majority of pastoralists neither possessed adequate knowledge about
      avian influenza nor applied adequate biosecurity measures against it, which are
      the most challenging gaps. Education of pastoralists on HPAI virus infection,
      specifically on information about clinical signs of avian influenza in birds,
      transmission dynamics among different species of birds, flyways of migrating wild
      birds and adequate mitigation measures are recommended.

PMID- 29067210
TI  - Pilot study of safety and feasibility of DNA microseeding for treatment of
      spontaneous canine melanoma.
AB  - Spontaneous canine malignant melanoma provides an excellent pre-clinical model to
      study DNA vaccines for melanoma immunotherapy. A USDA-approved xenogeneic human
      tyrosinase (huTYR) plasmid DNA vaccine delivered intramuscularly induces
      detectable immune responses and has clinical activity in some dogs with melanoma.
      The objective of this pilot study was to evaluate the feasibility, safety and
      immunogenicity of huTYR plasmid DNA administered to the skin via microseeding in
      dogs with spontaneous melanoma. DNA microseeding utilizes a modified tattooing
      device as an alternate and potentially more potent delivery method for DNA
      immunization. DNA was delivered to shaved inner thigh skin of six companion dogs
      with melanoma approximately every 14 days for a planned total of four vaccination
      time points. An anti-huTYR ELISA was used to test pre- and post-treatment sera.
      Biopsies of treated skin were obtained for detection of huTYR transgene
      expression. DNA microseeding was well tolerated with no significant toxicity
      detected beyond local site irritation, and there were no signs of autoimmunity.
      huTYR-expressing cells were observed in biopsies of huTYR DNA microseeding sites.
      Increased humoral anti-huTYR antibodies were seen in two of five evaluable dogs
      following microseeding compared to baseline. DNA microseeding is well tolerated
      in companion dogs with melanoma. Further investigation is needed to determine if
      combining DNA microseeding with other immunotherapy regimens potentiates this
      delivery platform for cancer immunotherapy.

PMID- 29067213
TI  - Assessment of clinical application of pulse oximetry probes in llamas and
      alpacas.
AB  - The placement and accuracy of pulse oximeter probes can vary markedly among
      species. For our study, we aimed to assess the accuracy of pulse oximetry and to
      determine the most clinically useful sites for probe placement in llamas and
      alpacas. The objectives included an analysis of pulse oximetry probes for
      accurate assessment of llamas and alpacas and to determine the best placement of
      the probes to achieve accurate readings. For study 1, saturation of haemoglobin
      with oxygen was measured in 184 arterial blood gas samples (SaO2) using a co
      oximeter and compared to saturation of haemoglobin with oxygen simultaneously
      measured using a pulse oximeter (SpO2). The bias and precision for the SpO2-SaO2
      difference was calculated and plotted on a Bland-Altman plot. For study 2, SpO2
      data was collected 624 times from a variety of sites [tongue (T), nasal septum
      (NS), lip (L), vulva (V), prepuce (P), ear (E), and scrotum (S)] and recorded
      based upon a percentage of successful readings. Results for study 1 revealed that
      SpO2 was consistently 0 to -6% points different than SaO2. The bias and precision
      of the SpO2-SaO2 difference was -2.6 +/- 1.7%. Results for study 2 uncovered that
      540 recordings were successful readings and were obtained from the tongue and
      nasal septum with 97% accuracy, the lip 80%, vulva 62%, prepuce 59%, ear and
      scrotum < 50%. We concluded that pulse oximetry probes provide reliable estimates
      of arterial haemoglobin oxygen saturation in llamas and alpacas and is most
      accurately read when placed on the nasal septum or tongue.

PMID- 29067214
TI  - Detailed statistical assessment of the characteristics of the ESMO Magnitude of
      Clinical Benefit Scale (ESMO-MCBS) threshold rules.
AB  - BACKGROUND: The European Society for Medical Oncology (ESMO) has developed the
      ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), a tool to assess the
      magnitude of clinical benefit from new cancer therapies. Grading is guided by a
      dual rule comparing the relative benefit (RB) and the absolute benefit (AB)
      achieved by the therapy to prespecified threshold values. The ESMO-MCBS v1.0 dual
      rule evaluates the RB of an experimental treatment based on the lower limit of
      the 95%CI (LL95%CI) for the hazard ratio (HR) along with an AB threshold. This
      dual rule addresses two goals: inclusiveness: not unfairly penalising
      experimental treatments from trials designed with adequate power targeting
      clinically meaningful relative benefit; and discernment: penalising trials
      designed to detect a small inconsequential benefit. METHODS: Based on 50 000
      simulations of plausible trial scenarios, the sensitivity and specificity of the
      LL95%CI rule and the ESMO-MCBS dual rule, the robustness of their characteristics
      for reasonable power and range of targeted and true HRs, are examined. The per
      cent acceptance of maximal preliminary grade is compared with other dual rules
      based on point estimate (PE) thresholds for RB. RESULTS: For particularly small
      or particularly large studies, the observed benefit needs to be relatively big
      for the ESMO-MCBS dual rule to be satisfied and the maximal grade awarded.
      Compared with approaches that evaluate RB using the PE thresholds, simulations
      demonstrate that the MCBS approach better exhibits the desired behaviour
      achieving the goals of both inclusiveness and discernment. CONCLUSIONS: RB
      assessment using the LL95%CI for HR rather than a PE threshold has two
      advantages: it diminishes the probability of excluding big benefit positive
      studies from achieving due credit and, when combined with the AB assessment, it
      increases the probability of downgrading a trial with a statistically significant
      but clinically insignificant observed benefit.

PMID- 29067215
TI  - Nivolumab-induced hypothyroidism and selective pituitary insufficiency in a
      patient with lung adenocarcinoma: a case report and review of the literature.
AB  - Immune checkpoint blockade including programmed cell death 1 pathway inhibition
      with agents such as nivolumab is gaining ground in a wide array of malignancies,
      so far demonstrating significantly improved survival rates even in metastatic,
      often multiply pretreated settings. Although targeted in nature and generally
      well-tolerated compared with conventional anticancer treatments, these agents are
      often linked to a newly emerged group of adverse reactions, referred to as immune
      related adverse events, which can also affect endocrine organs. This is a case
      report of a patient who received nivolumab for the treatment of recurrent
      metastatic non-small cell lung cancer and developed primary hypothyroidism and
      secondary adrenal insufficiency caused by selective pituitary dysfunction (with
      preservation of all other endocrine functions). After hormone replacement with
      daily administration of T4, T3 and hydrocortisone, the patient achieved complete
      recovery. Adequate characterisation of these rare yet potentially severe entities
      is essential for prompt diagnostic and therapeutic interventions that will permit
      us to fully benefit from these new agents' therapeutic potential.

PMID- 29067216
TI  - Genotyping tumour DNA in cerebrospinal fluid and plasma of a HER2-positive breast
      cancer patient with brain metastases.
AB  - BACKGROUND: Central nervous system (CNS) involvement contributes to significant
      morbidity and mortality in patients with human epidermal growth factor receptor 2
      (HER2)-positive metastatic breast cancer (mBC) and represents a major challenge
      for clinicians. Liquid biopsy of cerebrospinal fluid (CSF)-derived circulating
      tumour DNA (ctDNA) harbours clinically relevant genomic alterations in patients
      with CNS metastases and could be effective in tracking tumour evolution. METHODS:
      In a HER2-positive mBC patient with brain metastases, we applied droplet digital
      PCR (ddPCR) and next-generation whole exome sequencing (WES) analysis to measure
      ctDNA dynamic changes in CSF and plasma collected during treatment. RESULTS:
      Baseline CSF-derived ctDNA analysis revealed TP53 and PIK3CA mutations as well as
      ERBB2 and cMYC amplification. Post-treatment ctDNA analysis showed decreased
      markers level in plasma, consistent with extra-CNS disease control, while
      increased in the CSF, confirming poor treatment benefit in the CNS. DISCUSSION:
      Analysis of ctDNA in the CSF of HER2-positive mBC is feasible and could represent
      a useful companion for clinical management of brain metastases.

PMID- 29067217
TI  - Liquid biopsy for HER2-positive breast cancer brain metastasis: the role of the
      cerebrospinal fluid.

PMID- 29067218
TI  - Physical activity and prevention of Alzheimer's disease.

PMID- 29067219
TI  - Driving with Hemianopia V: Do Individuals with Hemianopia Spontaneously Adapt
      Their Gaze Scanning to Differing Hazard Detection Demands?
AB  - PURPOSE: We investigated whether people with homonymous hemianopia (HH) were able
      to spontaneously (without training or instructions) adapt their blind-side scan
      magnitudes in response to differing scanning requirements for detection of
      pedestrians in a driving simulator when differing cues about pedestrian
      eccentricities and movement behaviors were available in the seeing hemifield.
      METHODS: Twelve HH participants completed two sessions in a driving simulator
      pressing the horn when they detected a pedestrian. Stationary pedestrians outside
      the driving lane were presented in one session and approaching pedestrians on a
      collision course in the other. Gaze data were analyzed for pedestrians initially
      appearing at approximately 14 degrees  in the blind hemifield. No instructions
      were given regarding scanning. RESULTS: After appearing, the stationary
      pedestrians' eccentricity increased rapidly to a median of 31 degrees  after 2.5
      seconds, requiring increasingly larger blind-side gaze scans for detection, while
      the approaching pedestrians' eccentricity remained constant at approximately 14
      degrees , requiring a more moderate scan (~14 degrees ) for detection. Although
      median scan magnitudes did not differ between the two conditions (approaching: 14
      degrees  [IQR 9 degrees -15 degrees ]; stationary: 13 degrees  [IQR 9 degrees -20
      degrees ]; P = 0.43), three participants showed evidence of adapting (increasing)
      their blind-side scan magnitudes in the stationary condition. CONCLUSIONS: Three
      participants (25%) appeared to be able to apply voluntary cognitive control to
      modify their blind-side gaze scanning in response to the differing scanning
      requirements of the two conditions without explicit training. TRANSLATIONAL
      RELEVANCE: Our results suggest that only a minority of people with hemianopia are
      likely to be able to spontaneously adapt their blind-side scanning in response to
      rapidly changing and unpredictable situations in on-road driving.

PMID- 29067220
TI  - Familial Multiple Trichodiscomas: Case Report and Concise Review.
AB  - Familial multiple trichodiscomas is a condition characterized by multiple
      asymptomatic skin papules. The inheritance pattern has not been established. The
      skin lesions usually appear in childhood. The diagnosis of the cutaneous papules
      is established by pathologic evaluation. Birt-Hogg-Dube syndrome is excluded by
      not detecting any aberration in the folliculin gene locus. Including our patient,
      15 index individuals and their families are described. There is no systemic organ
      involvement or associated malignancies in individuals with this condition.

PMID- 29067221
TI  - Acute Calcific Tendinitis of the Longus Colli Muscle: Report of Two Cases and
      Review of the Literature.
AB  - Acute calcific tendinitis (ACT) of the longus colli muscle is a rare cause of
      debilitating neck pain. The ACT is presumed to be an aseptic inflammatory process
      of the superior oblique tendons of the longus colli muscle. It is often confused
      with other more concerning conditions including trauma, epidural abscess, disc
      herniation, and neoplasm. We present two cases of ACT and a brief literature
      review to stress the risk of misdiagnosis. A 38-year-old male presented with neck
      pain and stiffness accompanied by dysphagia. Computed tomography (CT) scan was
      done and the diagnosis was secured by demonstrating calcifications at the C1-C2
      level as well as the retropharyngeal effusion. A 53-year-old female was also
      complaining of neck pain and dysphagia. The CT scan demonstrated similar findings
      and the diagnosis was again clinched. Awareness of this unusual entity is
      essential to prevent unnecessary interventions.

PMID- 29067223
TI  - Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of
      Recurrent Clostridium Difficile Infection: A Literature Review.
AB  - Clostridium difficile (C. difficile) is a common cause of antibiotic--associated
      diarrhea (AAD), being responsible for 15--25% of all AAD cases. The purpose of
      this literature review is to determine the cost-effectiveness of fecal microbiota
      transplantation (FMT) and how it compares in this regard to the standard
      treatments of choice for recurrent C. difficile infection (CDI). The review of
      the literature along with the evaluation of three comparative cost effective
      analyses yielded findings consistent with the view that FMT is the most cost
      effective option in treating recurrent CDI. There are some (but considerably
      less) data indicating that FMT may be a cost effective strategy in treating
      initial CDI, as well. The superior cost-effectiveness of FMT as compared to the
      preferred standards of treatment for recurrent CDI suggest FMT use should become
      more integrated in routine clinical practice. Increased utilization of FMTs would
      allow for better control of this increasingly problematic disease as well as
      lower costs associated with its management.

PMID- 29067224
TI  - Combined Central Retinal Vein and Branch Retinal Artery Occlusion Post Intense
      Physical Activity.
AB  - We report a case of combined central retinal vein occlusion and branch retinal
      artery occlusion. A previously healthy 47-year-old male presented with decreased
      vision in the right eye after completing a half marathon. A fundus exam and
      retinal imaging revealed a combined central retinal vein and branch retinal
      artery occlusion. In the present report, we review the literature and discuss the
      possible mechanisms behind combined retinal vessel occlusions. To our knowledge,
      this is the first reported case of combined central retinal vein occlusion and
      branch retinal artery occlusion following intense exercise.

PMID- 29067222
TI  - Pathogenesis of Drug Induced Non-Allergic Angioedema: A Review of Unusual
      Etiologies.
AB  - Angioedema is the swelling of mucosal and sub-mucosal tissue. Typically, it
      manifests as the swelling of the face, lips, and tongue. Angioedema can be severe
      and life threatening when it involves the respiratory tract. Drug induced
      allergic angioedema and drug induced non-allergic angioedema differ in their
      mediator, their clinical presentations, and their management. In drug induced non
      allergic angioedema, symptoms are resistant to antihistamine and corticosteroid
      treatment. The aim of the analysis was to identify which medications are
      associated with drug-induced non-allergic angioedema and to understand the
      mechanism of action via which of these medication cause angioedema.

PMID- 29067225
TI  - Brain Tumor Causing Atrial Fibrillation in an Otherwise Healthy Patient.
AB  - We report a case of a 57-year-old man who presented with an episode of syncope
      resulting in an accident. On presentation, he was found to have atrial
      fibrillation (AF). A brain imaging done to exclude intracranial hemorrhage
      revealed a brain tumor instead. Recently, AF has been used as a marker for occult
      cancer. Thus, we hypothesize that AF in our patient was a result of the existing
      brain tumor and not simply a coincidence. AF may help in diagnosing brain tumors
      in asymptomatic or oligosymptomatic patients at an early stage, decreasing
      mortality and morbidity significantly.

PMID- 29067226
TI  - Dialysis: A Review of the Mechanisms Underlying Complications in the Management
      of Chronic Renal Failure.
AB  - Chronic renal failure (CRF) is the most prevalent, worldwide public health
      problem of the elderly population. The main cause of CRF is a damaged kidney.
      There are five stages of CRF based on the glomerular filtration rate (GFR), and
      stage 5 (GFR < 15 ml/min/1.73m2) is often called an end-stage renal disease
      (ESRD). In CRF, there is an accumulation of toxins and excess water due to
      compromised renal function. Dialysis is the preferred way to treat ESRD and
      remove accumulated toxins from the body. The cardiovascular risk associated with
      dialysis is 10 to 20 times higher in patients undergoing dialysis than in normal
      people. The inflamed kidneys and the process of dialysis also affect endothelial
      function, aggravating the risk of hypertension and cardiac problems. Therefore,
      both physicians and patients should be aware of the consequences of undergoing
      dialysis. There is an urgent need to educate CRF patients regarding facts about
      the disease, medications, dietary habits, and various measures required to manage
      the condition and lead a normal life. This paper attempts to delineate the
      mechanisms that could result in cardiovascular and other complications among CRF
      patients undergoing dialysis.

PMID- 29067227
TI  - Pseudomonas sp. BUP6 produces a thermotolerant alkaline lipase with trans
      esterification efficiency in producing biodiesel.
AB  - The present study describes the characteristics of a thermotolerant and alkaline
      lipase secreted by Pseudomonas sp. BUP6, a novel rumen bacterium isolated from
      Malabari goat, and its trans-esterification efficiency in producing biodiesel
      from used cooking oil (UCO). The extracellular lipase was purified to homogeneity
      (35.8 times purified with 14.8% yield) employing (NH4)2SO4 salt precipitation and
      Sephadex G-100 chromatography. The apparent molecular weight of this lipase on
      SDS-PAGE was 35 kDa, the identity of which was further confirmed by MALDI-TOF/MS.
      The purified lipase was found stable at a pH range of 7-9 with the maximum
      activity (707 U/ml) at pH 8.2; and was active at the temperature ranging from 35
      to 50  degrees C with the optimum at 45  degrees C (891 U/ml). Triton X-100 and
      EDTA had no effect on the activity of lipase; whereas SDS, Tween-80 and beta
      mercaptoethanol inhibited its activity significantly. Moreover, Ca2+ (1.0 mM)
      enhanced the activity of lipase (1428 U/ml) by 206% vis-a-vis initial activity;
      while Zn2+, Fe2+ and Cu2+ decreased the activity significantly. Using para
      nitrophenyl palmitate as substrate, the Km (11.6 mM) and Vmax [668.9
      MUmol/(min/mg)] of the purified lipase were also determined. Crude lipase was
      used for analyzing its trans-esterification efficiency with used cooking oil and
      methanol which resulted in the worthy yield of fatty acid methyl esters, FAME
      (45%) at 37  degrees C, indicating its prospects in biodiesel industry. Thus, the
      lipase secreted by the rumen bacterium, Pseudomonas sp. BUP6, offers great
      potentials to be used in various industries including the production of biodiesel
      by trans-esterification.

PMID- 29067228
TI  - A practical and evidence-based approach to management of inpatient diabetes in
      non-critically ill patients and special clinical populations.
AB  - Inpatient diabetes is a common medical problem encountered in up to 25-30% of
      hospitalized patients. Several prospective trials showed benefits of structured
      insulin therapy in managing inpatient hyperglycemia albeit in the expense of high
      hypoglycemia risk. These approaches, however, remain underutilized in hospital
      practice. In this review, we discuss clinical applications and limitations of
      current therapeutic strategies. Considerations for glycemic strategies in special
      clinical populations are also discussed. We suggest that given the complexity of
      inpatient glycemic control factors, the "one size fits all" approach should be
      modified to safe and less complex patient-centered evidence-based treatment
      strategies without compromising the treatment efficacy.

PMID- 29067229
TI  - Short-term effects of teriparatide versus placebo on bone biomarkers, structure,
      and fracture healing in women with lower-extremity stress fractures: A pilot
      study.
AB  - AIMS: In this pilot, placebo-controlled study, we evaluated whether brief
      administration of teriparatide (TPTD) in premenopausal women with lower-extremity
      stress fractures would increase markers of bone formation in advance of bone
      resorption, improve bone structure, and hasten fracture healing according to
      magnetic resonance imaging (MRI). METHODS: Premenopausal women with acute lower
      extremity stress fractures were randomized to injection of TPTD 20-ug
      subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for
      bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin
      (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen
      type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks.
      The area between the percent change of P1NP and CTX over study duration is
      defined as the anabolic window. To assess structural changes, peripheral
      quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks
      at the unaffected tibia and distal radius. The MRI of the affected bone assessed
      stress fracture healing at baseline and 8 weeks. RESULTS: After 8 weeks of
      treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo
      treated group (both p <= 0.01), resulting in a marked anabolic window (p <=
      0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger
      cortical area and thickness compared to placebo at the weight bearing tibial
      site, while placebo-treated women had a greater total tibia and cortical density.
      No changes at the radial sites were observed between groups. According to MRI,
      83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed
      stress fractures (p = 0.18). CONCLUSIONS: In this randomized, pilot study, brief
      administration of TPTD showed anabolic effects that TPTD may help hasten fracture
      healing in premenopausal women with lower-extremity stress fractures. Larger
      prospective studies are warranted to determine the effects of TPTD treatment on
      stress fracture healing in premenopausal women.

PMID- 29067230
TI  - Beta-cell function and insulin resistance among Peruvian adolescents with type 2
      diabetes.
AB  - OBJECTIVE: To characterize and compare the beta-cell function and insulin
      resistance among Peruvian adolescents with type 2 diabetes (T2D) and their non
      diabetic, overweight and lean peers. METHODS: Cross-sectional study of 54
      adolescents aged 10-19 years, distributed in three sex- and age-matched groups (n
      = 18): (i) adolescents with T2D; (ii) overweight adolescents without T2D; and
      (iii) lean adolescents without T2D, at the Diabetes, Obesity and Nutrition
      Research Center in Lima, Peru. Fasting glucose, insulin, C-peptide, and glycated
      hemoglobin were measured for all participants. In addition, a two-hour oral
      glucose tolerance test (OGTT, 1.75 mg of glucose/kg body weight) was performed,
      during which glucose and C-peptide were quantified. The homeostasis model
      assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) were
      derived for all participants, and beta-cell function was further examined by the
      area under the curve (AUC) of C-peptide. RESULTS: The median HOMA-IR score was
      higher in adolescents with T2D compared to lean adolescents (6.1 vs. 2.1; p =
      0.002), but was not different from that of overweight adolescents (6.1 vs. 4.0; p
      = 0.322). The median HOMA-B was higher in overweight adolescents than in lean
      adolescents (256.9 vs. 134.2; p = 0.015), and adolescents with T2D (256.9 vs.
      119.8; p = 0.011). The mean AUC of glucose in adolescents with T2D was 1.8-fold
      higher than that of overweight adolescents, and 1.9-fold higher than that of lean
      adolescents (p < 0.001). Although the median AUC of C-peptide in adolescents with
      T2D was lower than that of overweight and lean adolescents, this difference was
      not statistically significant (230.7 vs. 336.6 vs. 267.3 nmol/l120 min,
      respectively; p = 0.215). CONCLUSION: Among Peruvian adolescents with T2D,
      insulin resistance is the most prominent characteristic, rather than beta-cell
      dysfunction.

PMID- 29067231
TI  - Peripheral sensory neuropathy in type 2 diabetes patients: A case control study
      in Accra, Ghana.
AB  - OBJECTIVE: Peripheral sensory neuropathy (PSN) is a common cause of ulceration
      and amputation in diabetes (DM) patients. The prevalence of PSN in DM patients is
      largely undetermined in sub-Saharan African population. We studied the burden of
      PSN in DM patients using a validated questionnaire and quantitative sensory test.
      METHODS: In a case-control design, PSN was measured in 491 DM patients and 330
      non-DM controls using Michigan neuropathy screening instrument (MNSI) and
      vibration perception threshold (VPT). PSN was defined as MNSI symptom score >=7,
      MNSI examination score >=2 or VPT >=25V. RESULTS: The prevalence of PSN screened
      by MNSI symptom score, MNSI examination score and VPT was 7.1%, 51.5% and 24.5%
      in DM patients; and 1.5%, 24.5% and 8.5% in non-DM participants respectively. The
      major determinants of PSN screened by MNSI examination score were diabetes status
      [OR (95% CI): 4.31 (2.94-6.31), p < 0.001], age [1.03 (1.01-1.05), p < 0.001],
      previous [4.55 (2.11-9.82), p < 0.001] and current [8.16 (3.77-17.68), p < 0.001]
      smoking status. The major determinants of PSN screened by VPT were diabetes
      status [1.04 (1.02-1.06), p < 0.001], age [1.02 (1.01-1.03), p = 0.047], heart
      rate [1.78 (1.08-2.92), p = 0.023], second-hand smoking [3.66 (2.26-5.95), p <
      0.001] and body height [3.28 (1.65-8.42), p = 0.015]. CONCLUSION: Our study has
      shown high burden of PSN in DM patients in Ghana using simple, accurate, and non
      invasive screening tools like MNSI and neurothesiometer.

PMID- 29067232
TI  - Management of adynamic bone disease in chronic kidney disease: A brief review.
AB  - The Kidney Disease: Improving Global Outcomes (KDIGO) work group released
      recommendations in 2006 to define the bone-related pathology associated with
      chronic kidney disease as renal osteodystrophy. In 2009, KDIGO released revised
      clinical practice guidelines which redefined systemic disorders of bone and
      mineral metabolism due to chronic kidney disease as chronic kidney disease
      mineral and bone disorders. Conditions under this overarching term include
      osteitis fibrosa cystica, osteomalacia, and adynamic bone disease. We aim to
      provide a brief review of the histopathology, pathophysiology, epidemiology, and
      diagnostic features of adynamic bone disease, focusing on current trends in the
      management of this complex bone disorder.

PMID- 29067233
TI  - Effect of a macronutrient preload on blood glucose level and pregnancy outcome in
      gestational diabetes.
AB  - AIM: To investigate the effect of a macro-nutrient preload (Inzone Vitality) on
      blood glucose levels and pregnancy outcomes of gestational diabetes. The preload
      method involves the ingestion of a smaller amount of a macronutrient composition
      half an hour before regular meals. The hypothesis was that preload treatment will
      reduce postprandial glycemia in gestational diabetes. METHODS: Sixty-six
      diagnosed cases of gestational diabetes were randomly selected from gynecology
      and obstetrics outpatient clinic at Xinqiao Hospital in Chongqing. The patients
      were divided into an intervention group (33 cases) and a control group (33
      cases), according to odd-even numbers of the random cases. The intervention group
      was treated with a macro-nutrient preload given 0.5 h before regular meals and
      the control group was given a comparative treatment consisting of a milk powder
      with similar energy content. The two groups were studied until delivery and the
      measured parameters included fasting blood glucose (FBG), 2-hour postprandial
      blood glucose (2h-PBG), delivery mode and neonatal birth weight. RESULTS: The two
      groups showed no differences in FBG or 2h-PBG before the nutritional
      intervention. FBG and 2h-PBG after intervention and before delivery were
      significantly lower in the intervention group, treated with the macro nutrient
      preload compared to the control group (P < 0.01). Changes in FBG and 2h-PBG
      before and after the intervention were investigated and the difference in the
      intervention group was significantly greater than corresponding values in the
      control group (P < 0.05, P < 0.01). The neonatal birth weight and delivery mode
      was not significantly different (P > 0.05). CONCLUSION: A macro-nutrient
      composition, used as a preload, is effective in controlling FBG and PBG of
      gestational diabetes.

PMID- 29067234
TI  - Hypogonadism in thalassemia major patients.
AB  - Despite recent advances in iron chelation therapy, excess iron deposition in
      pituitary gonadotropic cells remains one of the major problems in thalassemic
      patients. Hypogonadism, mostly hypogonadotropic hypogonadism, is usually detected
      during puberty. Early diagnosis and treatment are crucial for normal pubertal
      development and to reduce the complications of hypogonadism. The risks and
      benefits of hormonal replacement therapy, especially regarding the thromboembolic
      event, remain a challenge for providers caring for thalassemic patients.

PMID- 29067236
TI  - American Diabetes Association meeting report.

PMID- 29067235
TI  - Severe hypoglycemia in patients with known diabetes requiring emergency
      department care: A report from an Italian multicenter study.
AB  - AIMS: To describe the characteristics and associated risk factors of patients
      with established diabetes who required Emergency Department (ED) care for severe
      hypoglycemia. METHODS: We performed an observational retrospective study to
      identify all cases of severe hypoglycemia among attendees at the EDs of three
      Italian University hospitals from January 2010 to December 2014. RESULTS:
      Overall, 520 patients with established diabetes were identified. Mean out-of
      hospital blood glucose concentrations at the time of the hypoglycemic event were
      2.2 +/- 1.3 mmol/L. Most of these patients were frail and had multiple
      comorbidities. They were treated with oral hypoglycemic drugs (43.6%), insulin
      (42.8%), or both (13.6%). Among the oral hypoglycemic drugs, glibenclamide
      (54.5%) and repaglinide (25.7%) were the two most frequently used drugs, followed
      by glimepiride (11.3%) and gliclazide (7.5%). Hospitalization rates and in
      hospital deaths occurred in 35.4% and in 2.3% of patients, respectively.
      Cirrhosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 1.24-36.8, p <
      0.05), chronic kidney disease (OR 2.42, 95% CI 1.11-8.69, p < 0.05) and center
      (Sapienza University OR 3.70, 95% CI 1.57-8.69, p < 0.05) were the strongest
      predictors of increased rates of hospital admission. CONCLUSIONS: Severe
      hypoglycemia is a remarkable burden for patients with established diabetes and
      increases the risk of adverse clinical outcomes (in-hospital death and
      hospitalization), mainly in elderly and frail patients. This study further
      reinforces the notion that careful attention should be taken by health care
      providers when they prescribe drug therapy in elderly patients with serious
      comorbidities.

PMID- 29067237
TI  - Ipragliflozin lowers small, dense low-density lipoprotein cholesterol levels in
      Japanese patients with type 2 diabetes mellitus.
AB  - AIMS: This preliminary randomized, parallel-group comparative study evaluated the
      efficacy of ipragliflozin for reduction of small dense low-density lipoprotein
      cholesterol (sd LDL-C) levels in Japanese patients with type 2 diabetes mellitus
      (T2DM). METHODS: Sixty-two patients with T2DM (age, 56 +/- 8 years; hemoglobin
      A1c levels, 8.1 +/- 0.9%; BMI, 27.5 +/- 3.3 kg/m2) were randomly assigned in a
      2:1 ratio to receive ipragliflozin (50 mg/day) (treatment group; n = 40) or
      continued treatment (control group; n = 22) for 12 weeks. The primary endpoints
      were changes in sd LDL-C levels detected using the LipoPhor AS(r) system; the
      secondary endpoints included changes in the sd LDL-C/large buoyant LDL-C (lb LDL
      C) ratio, a surrogate marker for LDL particle size, and percent changes in
      routine lipid parameters. RESULTS: The treatment group exhibited a statistically
      significant reduction from baseline for LDL-C levels (-0.37 mg/dL vs. 14.4 mg/dL,
      p = 0.038), sd LDL-C levels (-1.28 mg/dL vs. 2.81 mg/dL, p = 0.012), and sd LDL
      C/lb LDL-C ratio (-3.20% vs. 4.58%, p = 0.040) compared with the control group.
      Multiple regression analysis among all subjects revealed change in TG levels (p =
      0.011) and LDL-C levels (p = 0.024) as well as change in body weight (p = 0.006)
      as independent factors contributing to the reduction in sd LDL-C. CONCLUSIONS:
      Ipragliflozin may have a potential for lowering sd LDL-C levels associated with
      increasing LDL particle size in Japanese patients with T2DM.

PMID- 29067238
TI  - Lipid disorders in patients with renal failure: Role in cardiovascular events and
      progression of chronic kidney disease.
AB  - The spectrum of lipid disorders in chronic kidney disease (CKD) is usually
      characterized by high triglycerides and reduced high dense lipoprotein (HDL),
      associated with normal or slightly reduced low dense lipoprotein (LDL)
      cholesterol. This dyslipidemia is associated with an increased risk for
      atherosclerotic cardiovascular disease. Keys for the cardiovascular risk
      reduction in these patients are lowering the number and modifying the composition
      of the cholesterol-carrying atherogenic lipoprotein particles. Statins have an
      important role in primary prevention of cardiovascular events and mortality in
      non-hemodialyzed CKD patients. The benefits in terms of progression of renal
      failure are contradictory. Patient education regarding dietary regimen should be
      part of the CKD clinical management.

PMID- 29067239
TI  - Differences between genders in relation to factors associated with risk of
      diabetic foot in elderly persons: A cross-sectional trial.
AB  - AIMS: This trial aims to identify differences between genders in relation to
      factors associated with the risk of diabetic foot in elderly persons. METHODS: We
      evaluated 187 older adults diagnosed with diabetes type 2. The variables
      investigated were sociodemographic data, clinical history of diabetes mellitus
      and complaints about the feet. The plantar sensitivity was evaluated on both
      feet, with the use of Semmes-Weinstein monofilaments. For data analysis we used
      chi-square test and binary logistic regression (p < 0.05; 95% CI). RESULTS: We
      included 174 elderly people who had no history of stroke and peripheral vascular
      disease. Most (58.6%) were female and among them the risk factors for diabetic
      foot were older age (p < 0.021; OR 6.0), presence of calluses (p < 0.046; OR
      2.83) and claw toes (p < 0.041; OR 3.18). And among men, the risk factors for
      diabetic foot were insulin use (p < 0.008; OR 5.22), presence of sensory
      comorbidities (p < 0.007; OR 5.0), ulcers (p < 0.001), numbness (p < 0.002; OR
      6.6) and stiffness in the feet (p < 0.009; OR 5.44). CONCLUSION: The factors
      associated with the development of diabetic foot were presented differently in
      women and men, so a targeted and more specific preventive approach is required.

PMID- 29067241
TI  - Effect of phosphodiesterase-5 inhibitors on glycemic control in person with type
      2 diabetes mellitus: A systematic review and meta-analysis.
AB  - : Chronic use of phosphodiesterase-5 inhibitors (PDE-5i) has been shown to
      improve insulin action on muscle glucose uptake by the prolongation of nitric
      oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) signalling.
      AIMS: As the effects of PDE-5i on glycemic control in person with type 2 diabetes
      mellitus (T2DM) have not been systematically explored, we conducted a meta
      analysis of available randomized controlled trials (RCTs). METHODS: A literature
      search was performed through electronic databases including MEDLINE (Pubmed), The
      Cochrane Library, SCOPUS, Web of Science, CINAHL, www.clinicaltrials.gov and
      www.clinicaltrialresults.org until April 2016 without language restriction.
      Studies were included if they met the following criteria: (i) RCTs of the chronic
      use of PDE-5i compared with placebo or no active treatment in T2DM patients (ii)
      reporting of HbA1c or glycated haemoglobin or fasting plasma glucose (FPG).
      RESULTS: Four studies involving a total of 198 patients fit into the inclusion
      criteria. All included studies used the same PDE-5i, sildenafil. Reports of HbA1c
      were analysed as only one study reported FPG. PDE-5i had no beneficial effect on
      HbA1c with weighted mean difference (WMD) of 0.17% (95% CI, -0.64 to 0.97).
      CONCLUSION: This meta-analysis suggests that large and well-controlled studies
      are warranted to shed light on the effect of PDE-5i on glycemic control in people
      with type 2 diabetes mellitus.

PMID- 29067240
TI  - Benign thyroid disease in pregnancy: A state of the art review.
AB  - Thyroid dysfunction is the commonest endocrine disorder in pregnancy apart from
      diabetes. Thyroid hormones are essential for fetal brain development in the
      embryonic phase. Maternal thyroid dysfunction during pregnancy may have
      significant adverse maternal and fetal outcomes such as preterm delivery,
      preeclampsia, miscarriage and low birth weight. In this review we discuss the
      effect of thyroid disease on pregnancy and the current evidence on the management
      of different thyroid conditions in pregnancy and postpartum to improve fetal and
      neonatal outcomes, with special reference to existing guidelines on the topic
      which we dissect, critique and compare with each other. Overt hypothyroidism and
      hyperthyroidism should be treated appropriately in pregnancy, aiming to maintain
      euthyroidism. Subclinical hypothyroidism is often pragmatically treated with
      levothyroxine, although it has not been definitively proven whether this alters
      maternal or fetal outcomes. Subclinical hyperthyroidism does not usually require
      treatment and the possibility of non-thyroidal illness or gestational
      thyrotoxicosis should be considered. Autoimmune thyroid diseases tend to improve
      during pregnancy but commonly flare-up or emerge in the post-partum period.
      Accordingly, thyroid auto-antibodies tend to decrease with pregnancy progression.
      Postpartum thyroiditis should be managed based on the clinical symptoms rather
      than abnormal biochemical results.

PMID- 29067242
TI  - Impact of vitamin D status on statin-induced myopathy.
AB  - INTRODUCTION: There is a multitude of evidence supporting the benefit of statin
      use in cardiovascular disease; however, statin-induced myopathy is a major reason
      for statin discontinuation and non-adherence. Vitamin D deficiency has been
      independently associated with muscle weakness and severe myopathy, and may be a
      confounder for statin-induced myopathies. Since there is no consensus on a
      treatment course of action for statin-induced myopathy, investigation into
      potential confounders to elucidate the dynamics of statin-induced myopathy is
      warranted. METHODS: A retrospective chart review was conducted on 105 patients in
      a cardiometabolic clinic with a vitamin D drawn from December 2006 to April 2008.
      Patients exposed to statins were divided into two groups: (1) patients with low
      vitamin D (<32 ng/mL) [n = 52] and (2) patients with a sufficient vitamin D level
      (?32 ng/mL) [n = 32]. Data were compared via t-tests or Fisher's Exact, as
      appropriate. RESULTS: There were 41 statin-specific myopathies amongst the 24
      statin-intolerant patients. Low vitamin D was significantly associated with
      statin-induced myopathy (p = 0.048). Following prescription vitamin D
      supplementation, statin tolerance rates were significantly higher in patients
      with a baseline vitamin D ?20 ng/mL than those with a baseline vitamin D >20
      ng/mL (90% vs 33%; p = 0.036). CONCLUSION: Vitamin D status may be considered a
      modifiable risk factor for muscle-related adverse effects of statins, and
      supplementation of vitamin D (particularly when ?20 ng/mL) may improve statin
      tolerance.

PMID- 29067243
TI  - Treating psychological insulin resistance in type 2 diabetes.
AB  - AIMS: The phenomenon of psychological insulin resistance (PIR) has been well
      documented for two decades, but interventions to treat PIR have not been well
      described. The aim of this study was to describe interventions used to treat
      psychological insulin resistance by certified diabetes educators (CDE's).
      METHODS: A secondary data analysis study using empirical data from a trial (N =
      234) that included four CDEs providing counseling for psychological insulin
      resistance. Participants not currently using insulin completed the 10-item
      Barriers to Insulin Therapy measure. The four CDE interventionists documented
      their approach to addressing participants' barriers to taking insulin using a
      standard form. Recommendations were collated and summarized. RESULTS: Strong PIR
      was shown by 28.4% of participants reporting that they "would not start insulin"
      and a moderate degree of PIR was shown by 61.2% who said they "would be upset,
      but would start insulin." The CDE's treated PIR with four primary interventions:
      1) teaching and providing explanations, 2) demonstrations and sharing examples of
      success using insulin therapy, 3) return demonstrations, and 4) addressing
      feelings and positively managing expectations. CONCLUSION: This is the first
      study to describe in some detail potentially effective patient management
      strategies for PIR. A randomized controlled trial testing the efficacy of PIR
      interventions is needed.

PMID- 29067245
TI  - DNA methylation analysis in malignant pheochromocytoma and paraganglioma.
AB  - AIMS: In recent years, aberrant DNA methylation of specific CpG sites has been
      detected in many types of malignant tumors, and the epigenetic regulation of
      promoter CpG sites is considered an important mechanism underlying
      carcinogenesis. This study aimed to establish the epigenetics of the malignant
      transformation of malignant pheochromocytoma (PCC) and paraganglioma (PGL) by
      performing a methylation analysis. MATERIALS AND METHODS: Based on the results of
      the Infinium HumanMethylation450 BeadChip array using DNA samples of PCC/PGL
      patients, candidate CpG sites that were hyper/hypo-methylated in metastatic
      tumors relative to those in the primary tumors of 2 patients with malignant
      PCC/PGL were selected. The methylation levels of the chosen candidate CpG sites
      were evaluated quantitatively. RESULTS: Twelve CpG sites were selected as
      hypermethylated candidates, and 16 CpG sites were selected as hypomethylated
      candidates. Using two quantitative methylation analysis methods, one
      hypermethylated site (cg02119938) and one hypomethylated site (cg26870725)
      remained as candidates. These sites were related to ACSBG1 (acyl-CoA synthetase
      bubblegum family member 1) and MAST1 (microtubule-associated serine-threonine
      kinase 1), respectively. Immunohistochemical studies of ACSBG1 and MAST1 revealed
      that epigenetic changes in the malignant transformation of PCC/PGL might be
      associated with ACSBG1 silencing or MAST1 overexpression. CONCLUSIONS: Here, we
      report two noteworthy genes, ACSBG1 and MAST1; the aberrant promoter
      methylation/demethylation of these genes might be involved in their
      silencing/expression in malignant PCC/PGL. Further investigations are necessary
      to determine the role of ACSBG1 and/or MAST1 expression in malignant
      transformation and to establish pathological markers that can evaluate the
      malignant potential of PCC/PGL.

PMID- 29067244
TI  - Pre-heparin lipoprotein lipase mass as a potential mediator in the association
      between adiponectin and HDL-cholesterol in type 2 diabetes.
AB  - AIM: Lipoprotein lipase (LPL) is a major enzyme in lipid metabolism.
      Dyslipidemia, characterized by decreased high-density lipoprotein cholesterol
      (HDL-C), is prevalent in persons with type 2 diabetes mellitus (T2DM). The aim of
      this study was to determine whether pre-heparin LPL mass mediates the association
      between adiponectin and HDL-C in individuals with T2DM. METHODS: Pre-heparin LPL
      mass was measured via an enzyme-linked immunosorbent assay, adiponectin by
      radioimmunoassay, and HDL-C was determined enzymatically. Participants' (n = 50)
      demographics, HbA1c, adiposity, homeostasis model assessment for insulin
      resistance (HOMA-IR), serum creatinine, and lipids were measured. Path analysis
      was utilized to test whether pre-heparin LPL mass is a mediator in the
      relationship between adiponectin and HDL-C. RESULTS: All four criteria for
      mediation were satisfied in the path analysis. The indirect effect of adiponectin
      on HDL-C through pre-heparin LPL mass was significant, p = 0.001, whereas the
      direct effect of adiponectin on HDL-C was not significant, p = 0.074. These
      results remained consistent even after adjustments for age, gender, body mass
      index, HOMA-IR, and serum creatinine in the model. CONCLUSION: The findings in
      this study suggest that pre-heparin LPL mass may mediate the association between
      adiponectin and HDL-C in T2DM. This relationship for measures of HDL-C
      functionality requires future investigation.

PMID- 29067246
TI  - The interdisciplinary team in type 2 diabetes management: Challenges and best
      practice solutions from real-world scenarios.
AB  - The Global Partnership for Effective Diabetes Management has previously
      recommended the implementation of an interdisciplinary team (IDT) approach to
      type 2 diabetes (T2DM) management as one of 10 practical steps for health care
      professionals to help more people achieve their glycaemic goal. This article
      discusses some of the key contributors to success and also the challenges faced
      when applying IDT care, by examining case studies and examples from around the
      world. The real-world practices discussed show that implementing successful
      interdisciplinary care in diabetes is possible despite significant barriers such
      as established hierarchal structures and financial resource constraints.
      Instituting collaborative, integrated working relationships among multiple
      disciplines under strong leadership, together with enhanced and active
      communication and improved patient access to appropriate specialties is
      essential. Patients have a crucial role in the management of their own disease
      and including them as part of the treatment team is also critical. IDTs in
      diabetes care improve patient outcomes in terms of control of glycaemia and
      cardiometabolic risk factors, and decreased risk of diabetes complications.
      Ensuring access to an appropriate IDT, in whatever form, is paramount to enable
      the best care to be delivered.

PMID- 29067247
TI  - Migrant adults with diabetes in France: Influence of family migration.
AB  - AIM: To explore the influence of migration and this parameters on the control of
      diabetes. METHODS: A cohort of migrant patients with type 2 diabetes was
      recruited in a center affiliated to the French national insurance system situated
      in a department with important migratory phenomenon. Patients fulfilled a
      questionnaire about diabetes, their migration history, and the EPICES score
      (deprivation score). We have explored by univariate and multivariate analysis if
      any of the characteristics of migration could be related to the control of
      diabetes. This cohort was compared to a non-migrant control group of age and sex
      matched patients. RESULTS: We included 72 patients, 36 women and 36 men from 20
      different countries. The mean age was 57.7 +/- 9.6 years. A migration for family
      reunification was associated with better diabetes equilibrium (Risk of having an
      HbA1c ?8% (63.9 mmol/mol): OR 0.07 (95% IC [0.005-0.86], p = 0.04). The migrant
      patients who wished to share their time between France and country of origin
      during their retirement had a better glycaemic control than the migrant patients
      who would like to go alone into their country (OR 0.08 [0.01-0.78], p = 0.03).
      Compared to the non migrant group, the EPICES score was higher in the migrant
      group (52.8 vs. 28.3, p < 0.05), HbA1c was also higher in the migrant group (8.4
      vs. 6.7% (68 vs. 50 mmol/mol)). CONCLUSIONS: We may fear that migrants share an
      increased risk of uncontrolled diabetes. Individual migration could be a risk
      factor of uncontrolled diabetes. Knowing the migration history of migrant
      patients is fundamental to understand some barriers of care.

PMID- 29067248
TI  - The effect of text message support on diabetes self-management in developing
      countries - A randomised trial.
AB  - OBJECTIVE: mHealth interventions have the potential to facilitate self
      management. This TEXT4DSM study implemented a mobile phone intervention in
      existing diabetes programmes in three low- and middle-income countries
      (Democratic Republic of Congo, Cambodia, and the Philippines). RESEARCH DESIGN
      AND METHODS: Sub-studies with a similar randomised controlled trial design were
      conducted in three different countries. Each sub-study included 480 adults with
      diabetes. Subjects were randomised to receive either routine care or routine care
      plus text message self-management support. The primary outcome was the difference
      in the proportion of subjects with well-controlled diabetes after 2 years.
      RESULTS: Baseline and 2-year HbA1c measurements were available for 781
      individuals. After 2 years, the proportion of subjects with controlled HbA1c was
      2.8% higher in the intervention group than in the control group (difference not
      statistically significant). In the logistic regression model, the odds ratio for
      having controlled diabetes after the intervention was 1.1, after adjusting for
      baseline HbA1c level, sex, receiving insulin treatment, and participating in the
      routine programme. The HbA1c dynamics over time differed between programmes; the
      number of people with controlled diabetes tended to increase in DR Congo and
      decrease in Cambodia. CONCLUSION: This study was the first to test the same
      mHealth intervention in different countries. The finding that text messages did
      not show an additional effect on diabetes control implied that expectations about
      mHealth should be cautious. The degree of coverage, the quality of the routine
      programme, and the progression of disease can interfere with the expected impact.
      Trial registration: ISRCTN registry (86247213).

PMID- 29067249
TI  - Serum dehydroepiandrosterone sulfate in assessing the integrity of the
      hypothalamic-pituitary-adrenal axis.
AB  - OBJECTIVE: To evaluate the relationship between age- and gender-adjusted
      dehydroepiandrosterone sulfate (DHEA-S) levels and low-dose adrenocorticotropic
      hormone (ACTH) stimulation in assessing the integrity of the hypothalamic
      pituitary-adrenal (HPA) axis, in patients who were at risk of HPA insufficiency,
      including those currently being treated with glucocorticoids. METHODS: Forty-six
      participants with a suspicion of secondary adrenal insufficiency were recruited
      from the Diabetes and Endocrinology Clinic at Ramathibodi Hospital, Mahidol
      University, Bangkok. Low-dose (1 MUg) ACTH stimulation was performed in every
      participants, and serum DHEA-S was measured at baseline before ACTH injection.
      RESULTS: Individuals with normal age- and gender-specific DHEA-S levels had
      baseline serum cortisol and peak cortisol levels higher than those with reduced
      DHEA-S. Normal age- and gender-specific DHEA-S levels predicted intact HPA
      function with a sensitivity of 87.1%, a specificity of 86.7%, a positive
      predictive value of 93.1%, and a negative predictive value of 76.5%. To account
      for the age and gender dependency of DHEA-S, the DHEA-S ratio was calculated by
      measured DHEA-S divided by the lower limit of the respective reference range for
      all participants. A DHEA-S ratio of more than 1.78 had 100% sensitivity regarding
      intact HPA function. Area under the receiver operating characteristic [ROC] curve
      was 0.920. (95% CI, 0.844-0.997). CONCLUSION: Normal age- and gender-specific
      DHEA-S level or a DHEA-S ratio of more than 1.78 are valuable markers of HPA
      integrity. Serum DHEA-S may be a candidate for a less costly approach where ACTH
      stimulation is unavailable.

PMID- 29067250
TI  - Basal insulin therapy is associated with beneficial effects on postoperative
      infective complications, independently from circulating glucose levels in
      patients admitted for cardiac surgery.
AB  - BACKGROUND: Although hyperglycemia is a strong predictor of postoperative
      infective complications (PIC), little is known about the effect of basal insulin
      therapy (BIT) per se on PIC. AIM: To evaluate if there is an association between
      BIT, independent of glucose levels, and a possible improvement of PIC during the
      perioperative cardiosurgery period (PCP). METHODS: In 812 patients admitted for
      cardiac intervention and treated with a continuous intravenous insulin infusion
      (CIII) for hyperglycemic levels (>130 mg/dl), a retrospective analysis was
      performed during the PCP (January 2009-December 2011). Upon transfer to the
      cardiac surgery division, if fasting glucose was >=130 mg/dl, a basal + premeal
      insulin therapy was initiated (121 patients, group 1); for <130 mg/dl, a premeal
      insulin alone was initiated (691 patients, group 2). FINDINGS: Compared with
      group 2, group 1 showed reductions in PIC (2.48% vs 7.96%, p < 0.049; odds ratio:
      0.294; 95% CI: 0.110-0.780), C-Reactive Protein (p < 0.05) and white blood cell
      (p < 0.05) levels despite glucose levels and CIII that were higher during the
      first two days after surgery (179.8 +/- 25.3 vs 169.5 +/- 10.6 mg/dl, p < 0.01;
      0.046 +/- 0.008 vs 0.037 +/- 0.015 U/kg/h, p < 0.05, respectively). Normal
      glucose levels were achieved in both groups from day 3 before the discharge. The
      mean length of hospital duration was 18% lower in group 1 than in group 2 (7.21
      +/- 05.08 vs 8.76 +/- 9.08 days, p < 0.007), providing a significant impact on
      public health costs. CONCLUSIONS: Basal + preprandial insulin therapy was
      associated with a lower frequency of PIC than preprandial insulin therapy alone,
      suggesting a beneficial effect of basal insulin therapy on post-surgery outcome.

PMID- 29067251
TI  - Short-term effectiveness of a culturally tailored educational intervention on
      foot self-care among type 2 diabetes patients in Morocco.
AB  - BACKGROUND: Self-management education (SME) is an important yet unacknowledged
      aspect of diabetes care. Despite the raise of diabetes and its complications with
      significant burden in developing countries, research on SME interventions in
      Morocco is lacking. AIMS: To assess the effectiveness of a culturally tailored
      SME intervention on foot-care self-management practices among type 2 diabetes
      patients and to identify factors associated with practices variation. METHODS: We
      designed a pre-post prospective quasi-experimental study and recruited patients
      with type 2 diabetes aged 30 years old or above. The intervention consisted of an
      interactive group discussion using different materials: a narrative video, a
      PowerPoint presentation and a printed guide. Foot-care practices were assessed
      prior to the session and one month later using 2 items from the Summary of
      Diabetes Self-Care Activities (SDSCA). Binary logistic regression was performed
      to identify factors associated with a favorable variation, defined as an increase
      in the mean frequency score of foot-care by a minimum of 1 day/week. RESULTS: A
      total of 199 participants were recruited and 133 completed the second assessment.
      Mean age was 55.2 +/- 11.2 years old. Women represented 67% and 72% of
      participants was illiterate. The foot-care score mean increased from 3.5 +/- 2.9
      days to 5.9 +/- 1.8 days one month after the intervention (mean variation was 2.4
      +/- 3.1 days; p < 0.001). A favorable variation was found among 75 (37.7%)
      participants. In multivariate analysis, literacy was associated with higher
      likelihood of a favorable variation of foot-care practices (OR = 2.82; 95%CI:
      1.09-7.31) while previous education about diabetic foot was associated with lower
      likelihood of a favorable variation (OR = 0.26; 95%CI: 0.08-0.78). CONCLUSIONS:
      There was a general improvement in foot-care practices after the intervention.
      Our findings suggest the role of literacy and previous patient education in
      shaping the observed variation. Culturally tailored interventions targeting other
      disease management domains are needed in our context.

PMID- 29067252
TI  - Sense of Coherence is associated with LDL-cholesterol in patients with type 1
      diabetes - The PROLONG-Steno study.
AB  - AIM: It is a constant challenge for people with type 1 diabetes to maintain
      appropriate levels of HbA1c, blood pressure and blood lipids in order to prevent
      or delay deleterious effects of their illness. This study sought to investigate
      if Sense of Coherence (SOC) is associated with clinical risk factors in people
      with type 1 diabetes. METHODS: Questionnaire data, including measure of SOC, was
      collected from 125 patients with long duration of type 1 diabetes and linked to
      electronic patient records to obtain clinical measures on HbA1c, blood pressure,
      and blood lipids. Linear regressions and generalized additive models were applied
      to explore the associations between SOC and clinical biomarkers. RESULTS: Mean
      age of the participants was 60.7 years (standard deviation = 10.0), 44.0% were
      men. Medium and high SOC were associated with lower levels of LDL-cholesterol (p
      = 0.005). This association was non-linear with medium and high levels of SOC
      being advantageous whereas low SOC was associated with elevated levels of LDL
      cholesterol. Moreover, we observed non-significant tendencies to associations
      between low SOC and low HDL-cholesterol, and elevated HbA1c. CONCLUSIONS:
      Findings from this study suggest that high SOC may be protective against elevated
      LDL-cholesterol among people with type 1 diabetes. Interventions to improve self
      management among people with low SOC may prove effective to prevent deterioration
      of metabolic risk factors.

PMID- 29067253
TI  - Evidence-based review of statin use in patients with HIV on antiretroviral
      therapy.
AB  - INTRODUCTION: As a result of improved safe and effective therapeutic options for
      human immunodeficiency virus (HIV), life expectancy of those living with HIV is
      increasing leading to new challenges (e.g., management of chronic diseases). Some
      chronic diseases (e.g., cardiovascular disease [CVD]), are up to two times more
      prevalent in patients with HIV. Statins are a mainstay of therapy for prevention
      of CVD; but, clinicians should be aware that not all statins are appropriate for
      use in the HIV population, especially those receiving antiretroviral therapy
      (ART). The purpose of this article is to review the pharmacokinetic and clinical
      data for statin therapy in HIV-infected patients receiving ART. METHODS: A
      systematic literature search using PubMed and MEDLINE databases was performed
      using each statin drug name combined with HIV, pharmacokinetics, AIDS, and/or
      human immunodeficiency virus. English language trials published from 1946 to
      November 2016 were considered, and results were limited to clinical efficacy
      trials. RESULTS: In general, atorvastatin and pravastatin are safe and effective
      for patients treated with protease-inhibitor (PI) or non-nucleoside reverse
      transcriptase inhibitor-based ART. Rosuvastatin is generally considered safe if
      started at a low dose, but should be avoided if possible in patients receiving PI
      based ART. Pitavastatin has limited supporting evidence, but appears safe for use
      based on its pharmacokinetic properties and low number of drug interactions.
      Fluvastatin, lovastatin, and simvastatin should be avoided in patients receiving
      ART due to drug interactions, adverse events, and/or limited clinical data.
      CONCLUSION: Clinicians need to be familiar with the intricacies of statin
      selection for the prevention of CVD in patients with HIV on ART.

PMID- 29067254
TI  - Temporal trend of autonomic nerve function and HSP27, MIF and PAI-1 in type 1
      diabetes.
AB  - AIM: Diabetes mellitus type 1 (T1D) has numerous complications including
      autonomic neuropathy, i.e. dysfunction of the autonomous nervous system. This
      study focuses on Heat Shock Protein 27 (HSP27), Macrophage Migration Inhibitory
      Factor (MIF), Plasminogen Activator Inhibitor-1 (PAI-1) and HbA1c and their
      possible roles in effects of diabetes on the autonomic nervous system. METHODS:
      Patients with T1D (n = 32, 41% women) were recruited in 1985 and followed up on
      four occasions (1989, 1993, 1998, and 2005). Autonomic function was tested using
      expiration/inspiration (E/I-ratio). Blood samples, i.e. HSP27 (last three
      occasions), MIF, PAI-1 (last two occasions) and HbA1c (five occasions), were
      analyzed. RESULTS: Autonomic nerve function deteriorated over time during the 20
      year-period, but levels of HSP27, MIF, and PAI-1 were not associated with
      cardiovascular autonomic neuropathy. MIF and PAI-1 were lower in T1D than in
      healthy controls in 2005. Increased HbA1c correlated with a decrease in E/I
      ratio. CONCLUSIONS: Neither the neuroprotective substance HSP27 nor the
      inflammatory substances, MIF and PAI-1 were associated with measures of
      cardiovascular autonomic nerve function, but a deterioration of such function was
      observed in relation to increasing HbA1c in T1D during a 20-year follow-up
      period. Improved glucose control might be associated with protection against
      autonomic neuropathy in T1D.

PMID- 29067255
TI  - Relationship between retinal vessel diameters and retinopathy in the Inter99 Eye
      Study.
AB  - PURPOSE: To examine the association between retinal vessel diameters and
      retinopathy in participants with and without type 2 diabetes in a Danish
      population-based cohort. METHODS: The study included 878 persons aged 30 to 60
      years from the Inter99 Eye Study. Retinopathy was defined as a presence of one or
      more retinal hemorrhages or one or more microaneurysms. Vessel diameters were
      expressed as central retinal artery equivalent diameter (CRAE) and central
      retinal vein equivalent diameter (CRVE). Multiple linear regression analyses were
      performed. RESULTS: Among participants with diabetes, CRAE was 6.3 um (CI 95%:
      1.0 to 11.6, p = 0.020) wider and CRVE was 7.9 um (CI 95%: 0.7 to 15.2, p =
      0.030) wider in those with retinopathy compared to those without retinopathy,
      after adjusting for age, gender, HbA1c, blood pressure, smoking, serum total and
      HDL cholesterol. In all participants, CRAE increased with presence of retinopathy
      (p = 0.005) and with smoking (p = 0.001), and CRAE decreased with hypertension (p
      < 0.001), high HDL cholesterol (p = 0.016) and age (p < 0.001). Central retinal
      vein equivalent diameter increased with presence of retinopathy (p = 0.022) and
      with smoking (p < 0.001), and decreased with higher HDL cholesterol (p < 0.001)
      and age (p = 0.015). Female gender was associated with wider CRVE (p = 0.029).
      CONCLUSIONS: Wider retinal vessel diameters were associated with the presence of
      retinopathy in participants with diabetes, but not in participants without
      diabetes. The associations between retinal vessel diameters and known retinopathy
      risk factors were confirmed. These results suggest that information obtained by
      non-invasive imaging of the interior of the eye can contribute to a better
      understanding of systemic disease processes.

PMID- 29067256
TI  - The effect of diabetes case management and Diabetes Resource Nurse program on
      readmissions of patients with diabetes mellitus.
AB  - AIMS: Patients with diabetes have higher readmission rates than those without
      diabetes, yet limited data on efforts to reduce their readmissions are available.
      We describe a novel model of inpatient diabetes care, expanding the role of
      diabetes educators to include case management, and establishment of a Diabetes
      Resource Nurse program, aimed at increasing the knowledge of staff nurses, and
      evaluate the impact of this program on readmission rates. METHODS: We performed
      retrospective analysis of 30-day readmission rates of patients with diabetes
      before (July 2010-December 2011), and after (January 2012-June 2013) starting the
      implementation of this tiered inpatient diabetes care delivery model. RESULTS: We
      analyzed 34,472 discharged patient records from the 18-month pre-intervention
      period, and 32,046 records from the 18-month post-intervention period. The
      overall 30-day readmission rate for patients with diabetes decreased
      significantly from 20.1% (pre) to 17.6% (post) intervention (p < 0.0001).
      Patients seen by diabetes educators had the lowest 30-day readmission rates (~15%
      during the whole study), a rate approaching the overall hospital readmission
      rates in those without diabetes in our institution. CONCLUSION: The Diabetes
      Resource Nurse program is effective in decreasing readmission rates. Patients
      seen by the diabetes educators have the lowest rates of readmission.

PMID- 29067257
TI  - A study of serum IgG4 levels in the clinical metamorphosis of autoimmune thyroid
      disease.
AB  - BACKGROUND: Measurement of serum IgG4 had been suggested to distinguish the
      unique subtypes of autoimmune thyroid disease (AITD) which demonstrated patterns
      of fluctuating between hyperthyroidism and hypothyroidism. However, the clinical
      utility of serum IgG4 measurement is inconclusive due to few studies having
      addressed these unusual patients compared with the specificity of serum IgG4 in
      healthy patients. AIM: To investigate whether elevated serum IgG4 levels could be
      used as a marker to identify fluctuating AITD patients. MATERIALS AND METHODS: 20
      AITD patients who evolved from hyperthyroid Graves' disease to spontaneous
      hypothyroidism or vice versa were compared with 40 healthy subjects, 40 patients
      with hyperthyroid Graves' disease (GD) and 40 patients with subclinical or overt
      hypothyroid Hashimoto's thyroiditis (HT). Serum levels of total IgG and IgG4 were
      measured and the proportion of elevated serum IgG4 levels (defined by serum IgG4
      levels >= 135 mg/dL) was compared with control patients. RESULTS: A series of 20
      Thai patients with clinical evolution of AITD was analyzed with a median follow
      up at 92 months (range 3-380 months). Elevated serum IgG4 levels were not found
      in fluctuating AITD patients but were found in 5% of the control GD patients,
      2.5% of the control HT, and 2.5% of healthy subjects which were not statistically
      significant between each group. CONCLUSION: Our results contrasted with those of
      previous studies from Japan which reported elevated serum IgG4 as a marker to
      identify subset of AITD patients. At present, the clinical utility of serum IgG4
      measurements in AITD is inconclusive and requires further investigation.

PMID- 29067258
TI  - Serum 25-hydroxyvitamin D but not dietary vitamin D intake is associated with
      hemoglobin in women of reproductive age in rural northern Vietnam.
AB  - BACKGROUND AND OBJECTIVES: Hypovitaminosis D and anemia are both prevalent in
      Vietnam, and low vitamin D status may be a risk factor for anemia. This study
      aimed to 1) describe vitamin D intake and its determinants, and 2) examine the
      associations of vitamin D intake and serum 25(OH)D concentrations with hemoglobin
      and anemia. METHODS AND STUDY DESIGN: We used data from the baseline survey of a
      pre-conceptual micronutrient supplementation trial in women of reproductive age
      (WRA) in Thai Nguyen, Vietnam (N = 4961). Vitamin D intake was estimated using a
      semi-quantitative food frequency questionnaire (FFQ). Multivariable regression
      models were used for the analyses. RESULTS: Median vitamin D intake was 0.2 ug/d
      (8.0 IU) [IQR: 0.4]. Age, being a farmer, food insecurity, and body mass index
      (BMI) were inversely associated with vitamin D intake, while socioeconomic status
      (SES), total energy intake, and education were positively associated with vitamin
      D intake. Vitamin D intake was not associated with hemoglobin concentration or
      anemia after adjusting for age, BMI, total energy intake, transferrin receptor, C
      reactive protein, alpha1-acid glycoprotein, SES, occupation, education,
      ethnicity, and food insecurity (P = 0.56 and P = 0.65 for hemoglobin and anemia,
      respectively). Controlling for the same covariates, 25(OH)D <50 nmol/L (vs. >=50
      nmol/L) was associated with decreased hemoglobin concentrations (beta = -0.91
      (SE:0.42), P = 0.03), but not with anemia (P = 0.11). CONCLUSIONS: Low vitamin D
      status may be linked to reduced hemoglobin concentrations, but the role of diet
      in this association was not evident in this population of WRA in Vietnam where
      dietary vitamin D intake was very low.

PMID- 29067259
TI  - The Barbados Insulin Matters (BIM) study: Barriers to insulin therapy among a
      population-based sample of people with type 2 diabetes in the Caribbean island of
      Barbados.
AB  - AIM: The purpose of this study was to document in people with type 2 diabetes
      (T2DM) in Barbados, attitudes and beliefs that may result in psychological
      insulin resistance. METHODS: A representative, population-based, sample of 175
      eligible people with T2DM 25 years of age and over was surveyed by telephone. The
      20-item insulin treatment appraisal scale (ITAS) was administered (score range 20
      to 100 for positive to negative perceptions). RESULTS: 117 people participated
      (67% response rate, 32% male, mean age 66 years, 90% Black, 22% on insulin). Of
      non-responders, 52 were not contactable and 6 were difficult to communicate with.
      Negative perceptions about insulin use included - meant a worsening of diabetes
      (68%), would worry family (63%), feared self-injection (58%), meant a failure in
      self-management (57%), injections were painful (54%), would be seen as being
      sicker (46%), increased hypoglycaemia risk (38%), required effort (34%), causes
      weight gain (27%), causes a deterioration in health (14%), and would have to give
      up enjoyable activities (10%). Positive perceptions were - helps good glycaemic
      control (78%), would prevent complications (61%) and improves health (58%). Mean
      total ITAS score (61.6, SD = 7.7) was lower for those on insulin compared to
      those not on insulin (53.7 vs. 63.8, p < 0.0001). Sex, age and diabetes diagnosis
      duration were not significant predictors of ITAS score. CONCLUSIONS: Multiple
      factors related to patient beliefs and attitudes need to be considered and
      addressed when initiating insulin in order to minimise psychological insulin
      resistance and delay. Patients using insulin had less negative perceptions than
      those not on insulin.

PMID- 29067260
TI  - A review of current models for initiating injectable therapy for people with type
      2 diabetes in primary care.
AB  - AIMS: To systematically identify and describe models of injectable therapy
      initiation for people with type 2 diabetes mellitus (T2DM) in primary care.
      METHODS: Eight electronic databases and the grey literature were searched.
      Studies examining models of injectable therapy initiation for adults with T2DM in
      primary care settings were included. RESULTS: Successful models included: 1)
      Nurse-led one-to-one approach; 2) Nurse-led group sessions; and 3) Providing
      education to GPs and nurses. CONCLUSIONS: Few robust studies were found. Studied
      models were mainly in general practices, with limited evidence documented about
      starting people with T2DM on an injectable in the home setting.

PMID- 29067261
TI  - Active cocaine use does not increase the likelihood of hyperglycemic crisis.
AB  - OBJECTIVE: Hyperglycemic crisis encompasses a group of diabetes emergencies
      characterized by insulin deficiency with high morbidity and mortality. Cocaine
      use is increasingly prevalent in the United States and may be associated with
      increased risk of diabetic ketoacidosis. The objective was to determine if active
      cocaine use at hospital admission could be considered a risk factor for
      development of hyperglycemic crisis. METHODS: A retrospective case-control
      analysis was performed on 950 inpatients with hyperglycemia at an urban academic
      hospital. Patients admitted with non-emergent hyperglycemia were compared to
      patients who met criteria for diabetic ketoacidosis (DKA), hyperosmolar
      hyperglycemic state (HHS), and hyperosmolar ketoacidosis (HK), based on the
      absence or presence of cocaine metabolites on urine toxicology screen. Outcomes
      included frequency of cocaine use in patients with DKA, HHS, HK, and non-emergent
      hyperglycemia; phenotypic characteristics of cocaine users vs. non-users with
      hyperglycemia; phenotypic characteristics of patients with hyperglycemic crisis
      vs. non-emergent hyperglycemia. RESULTS: 950 patients were admitted with
      hyperglycemia, 133 of which met criteria for hyperglycemic crisis. There was no
      significant difference in the frequency of cocaine use in individuals with non
      emergent hyperglycemia compared to individuals with hyperglycemic crisis (16.9%
      vs. 17.2%, p = 0.90). 16.9% of patients with DKA, 16.4% of patients with HHS, and
      6.4% of patients with HK were cocaine users. CONCLUSIONS: We found no association
      between active cocaine use at the time of hospital admission and development of
      hyperglycemic crisis, when compared to non-emergent hyperglycemia. The role of
      routine screening for cocaine use in patients with hyperglycemic crisis is
      unclear.

PMID- 29067263
TI  - Survey of vaccination practices in patients with diabetes: A report examining
      patient and provider perceptions and barriers.
AB  - In a cross-sectional study involving 279 patients with diabetes attending a
      primary care center the proportion of patients vaccinated for seasonal influenza,
      pneumococcus and hepatitis B was 40%, 2% and 2%, respectively. We found
      significant barriers for vaccination in 24% of patients and in 42% of providers.

PMID- 29067264
TI  - Outpatient management of steroid-induced hyperglycaemia and steroid-induced
      diabetes in people with lymphoproliferative disorders treated with intermittent
      high dose steroids.
AB  - High dose steroids (HDS) are used in the treatment of haematological
      malignancies. The reported risk of steroid-induced diabetes (SID) is high.
      However, screening is not consistently performed. We implemented a protocol for
      detection and management of SID and steroid-induced hyperglycamia (SIH) in
      haematology outpatients receiving HDS. Eighty-three people were diagnosed with a
      lymphoproliferative disorder, of whom 6 had known Type 2 diabetes. Fifty-three
      people without known diabetes were screened by HbA1c and random venous plasma
      glucose. All patients (n = 34) subsequently prescribed HDS checked capillary
      blood glucose (CBG) pre-breakfast and pre-evening meal. Treatment algorithms used
      initiation and/or dose titration of gliclazide or human NPH insulin, aiming for
      pre-meal CBG 5-11 mmol/l. Type 2 diabetes was identified in 4/53 people screened
      (7.5%). Of 34 people treated with HDS, 17 (44%) developed SIH/SID. All 7 people
      with Type 2 diabetes developed SIH and 3 required insulin. Of 27 people without
      known diabetes, 8 (30%) developed SID and 1 required insulin. Pre-treatment HbA1c
      was higher in people who developed SID compared to those that did not (p =
      0.002). This is the first report of a SID/SIH detection and treatment protocol
      for use in people with lymphoproliferative disorders receiving intermittent HDS,
      demonstrating its feasibility and safety.

PMID- 29067262
TI  - Physical inactivity and cardiac events: An analysis of the Detection of Ischemia
      in Asymptomatic Diabetics (DIAD) study.
AB  - AIMS: Diabetes affects 29 million adults, and the majority have type 2 diabetes
      (T2D). Coronary artery disease (CAD) is the leading cause of death, and physical
      inactivity is an important risk factor. The aims of this study were to examine
      the contribution of physical inactivity to CAD events, and to identify the
      independent predictors of CAD events in a sample of older adults with T2D.
      METHOD: A secondary data analysis of the prospective randomized screening trial
      "Detection of Ischemia in Asymptomatic Diabetics (DIAD)" study. Cox proportional
      hazard modeling was used to examine the outcome of CAD events. RESULTS: During
      the five years of follow-up, the CAD event rate for all subjects (n = 1119) was
      8.4% (n = 94). In unadjusted analysis, physical inactivity was significantly
      associated with development of a CAD event. In the final model, nine baseline
      variables were significant predictors (p < 0.05) of a CAD: physical inactivity,
      race, diabetes duration, hemoglobin A1c (HbA1c), peripheral numbness, insulin
      use, increasing waist-to-hip ratio, family history of premature CAD, and a higher
      pulse pressure. In men only, there were five predictors (p < 0.05) of a CAD
      event: diabetes duration, peripheral numbness, HbA1c, increasing waist-to-hip
      ratio, and higher pulse pressure. The final model in women included three
      independent predictors (p < 0.05) of a CAD event: diabetes duration, a family
      history of premature CAD, and higher pulse pressure. CONCLUSION: Several
      variables predicted CAD events in this sample of older adults with T2D.
      Understanding baseline characteristics that heighten risk may assist providers in
      intervening early to prevent its occurrence.

PMID- 29067265
TI  - High prevalence of diabetes and abnormal glucose tolerance in Thai women with
      previous gestational diabetes mellitus.
AB  - AIM: To determine the prevalence of and risk factors for abnormal glucose
      tolerance (AGT) in previous gestational diabetes mellitus (pGDM) women. METHODS:
      100 pGDM women randomly selected from the database of the Department of
      Obstetrics/Gynecology. 75 g-OGTT were performed in subjects without known
      diabetes. AGT was diagnosed using the American Diabetes Association criteria.
      RESULTS: The mean age, pre-gestational BMI, and time since delivery were 38 +/- 5
      years, 24.5 +/- 5.7 kg/m2, and 46 +/- 26 months. Overall, 81% of the subjects had
      AGT, including IGT (38%), IGT + IFG (5%), T2DM (38%). Plasma glucose (PG) at 1 h
      after a 50 g-glucose challenge test (GCT), PG at 1 h after 100 g-OGTT, HbA1c, and
      HOMA-IR were significantly greater in women with AGT than normal glucose
      tolerance (NGT) women. The proportion of women with >=3 abnormal PG values during
      100 g-OGTT was greater in AGT than NGT group (50.7% vs. 15.8%). Multivariate
      analysis showed that PG >= 150 mg/dl at 1 h after a 50 g-GCT and >=3 abnormal PG
      values in 100 g-OGTTs were risk factors for developing AGT. CONCLUSIONS: Eighty
      one percent of pGDM women developed AGT within 4 years after delivery. Risk
      factors for AGT were PG >= 150 mg/dl at 1 h after a 50 g-GCT and >=3 abnormal PG
      values in a 100 g-OGTT.

PMID- 29067266
TI  - The association between vitamin D level and diabetic peripheral neuropathy in
      patients with type 2 diabetes mellitus: An update systematic review and meta
      analysis.
AB  - AIM: Recently, increasing studies have been carried out to explore the
      association between vitamin D level and the development of diabetic peripheral
      neuropathy (DPN) in patients with diabetes mellitus (DM). However, because of the
      shortcoming in study design and sample size, there is still no clear conclusion.
      We performed this meta-analysis to examine the exact impact of vitamin D
      deficiency on DPN in type 2 diabetic patients. METHODS: Various databases were
      searched to identify the potential articles which explored the association
      between vitamin D level and diabetic peripheral neuropathy in type 2 diabetes. We
      pooled OR to assess the correlation between vitamin D deficiency and DPN using
      the random-effects model. The standardized mean difference (SMD) with 95% CI of
      vitamin D was also calculated to evaluate the vitamin D level between DPN and non
      DPN in T2DM. RESULTS: There was obvious heterogeneity in those included ten
      studies (I2 = 94.1%, Cochran Q test P < 0.001) using mean and standard deviation
      (SD) of vitamin D level. In Caucasian, vitamin D level was significantly lower in
      DPN patients compared with diabetic patients without DPN (SMD = -0.56, I2 =
      16.9%). In Asian, the pooled OR value of vitamin D deficiency was 1.22 (95%CI:
      1.17-1.27). Sensitivity analysis showed one study had great influence on this
      meta-analysis and it still existed after excluded that one. There was no evidence
      of public bias in meta analysis as showed in Begg test and Egger test.
      CONCLUSION: This meta-analysis indicates that vitamin D deficiency is associated
      with the generation and development of DPN in Caucasian with T2DM, and in Asian,
      diabetic patients with vitamin D deficiency are 1.22 times to suffer from DPN
      compared with normal vitamin D level. Vitamin D supplementation is urgently
      needed to prevent the development of DPN in T2DM.

PMID- 29067267
TI  - Diabetic osteoarthropathy care in Sweden - Need for improvement: A national
      inventory.
AB  - AIMS: Osteoarthropathy, a rare foot complication in patients with diabetes
      mellitus, calls for immediate and optimal management to prevent irreversible
      bone/joint destruction and risk of amputation. Awareness of the condition and
      adequate guidelines would minimize the consequences and the costs, both for the
      patient and for the society. We investigated the diabetic osteoarthropathy care
      in Swedish orthopedic clinics. METHODS: A questionnaire was distributed to 63
      Swedish hospitals with emergency department for orthopedic patients. There was a
      95% response rate. RESULTS: Most of the respondents (79%) specified absence of
      established procedures including guidelines for managing patients with
      osteoarthropathy. The most common diagnostic method was clinical diagnosis and
      plain X-ray (95%). MRI or scintigraphy was used by 19% and 10.5% respectively. As
      treatment method, 84% used a total contact cast, while 38% used orthoses.
      Treatment duration <3 months was reported in 4%, 3-6 months in 53% and 6-12
      months in 28% of the clinics. Four clinics reported treatment duration >12 months
      and two clinics provided no treatment. CONCLUSION: Our national inventory
      indicates a need for improvement in knowledge as well as guidance and
      organization at orthopedic clinics regarding optimal care of patients with
      diabetic osteoarthropathy.

PMID- 29067268
TI  - Prognostic indicators for the development of strabismus among patients with
      graves' ophthalmopathy.
AB  - OBJECTIVE: Thyroid eye disease (TED), an autoimmune inflammatory process
      involving the orbital tissues around the eye, is the most common extra-thyroidal
      manifestation of Graves' disease (GD). Due to changes in the patient's
      appearance, TED is a socially and visually disabling condition with significant
      impacts on quality of life. The aim of this study is to assess predictors of
      strabismus, a severe manifestation of TED. DESIGN: Single-institution
      retrospective case-control study. Cases of Graves' ophthalmopathy patients with
      strabismus were matched 1:1 to controls of Graves' ophthalmopathy patients
      without strabismus by age and sex. PATIENTS: Patients >=18 years old with severe
      Graves' ophthalmopathy who received their medical care at UCLA with strabismus
      between 2012 and 2015. MEASUREMENTS: Eligibility criteria for cases was a
      diagnosis of Graves' ophthalmopathy with a subsequent diagnosis of strabismus.
      Using conditional logistic regression, the odds ratios of developing strabismus
      following the diagnosis of Graves' disease were assessed. The prognostic
      indicators assessed include race, ethnicity, cigarette smoking (active), serum
      thyroid peroxidase (TPO) antibody positivity, serum thyroglobulin (Tg) antibody
      positivity, antithyroidal medication use, and steroid use. RESULTS: The study
      sample (45 cases 1:1 matched against 45 controls) was comprised primarily of non
      Hispanic, non-Latino Caucasian women with TED (mean +/- SD age 63.0 +/- 13.1
      years). There were no significant predictors for the development of strabismus,
      including cigarette smoking (active), serum thyroid peroxidase (TPO) antibody
      positivity, serum thyroglobulin (Tg) antibody positivity, antithyroidal
      medication, and steroid use. CONCLUSIONS: No significant predictors of
      strabismus, a severe manifestation of Graves' ophthalmopathy, were identified
      following a diagnosis of TED in this study.

PMID- 29067269
TI  - The influence of diabetes distress on digital interventions for diabetes
      management in vulnerable people with type 2 diabetes: A qualitative study of
      patient perspectives.
AB  - BACKGROUND: Digital interventions for improving diabetes management in Type 2
      diabetes mellitus (T2DM) are used universally. Digital interventions are defined
      as any intervention accessed and taking input from people with T2DM in the form
      of a web-based or mobile phone-based app to improve diabetes self-management.
      However, the current confidence in digital interventions threatens to augment
      social inequalities in health, also known as the "digital divide". To counteract
      dissemination of the digital divide, we aimed to assess the potential of a
      tailored digital intervention for improving diabetes management in vulnerable
      people with T2DM. METHODS: A qualitative design using semi-structured in-depth
      interviews to explore the perspectives of 12 vulnerable people with T2DM.
      Interviews were analyzed using inductive content analysis. Vulnerability was
      defined by the presence of one or more comorbidities, one or more lifestyle risk
      factors, poor diabetes management, low educational level and low health literacy.
      RESULTS: The main themes identified were: "Dealing with diabetes distress"
      characterized by psychological avoidance mechanisms; "Suffering informational
      confusion" dealing with inconsistent information; "Experiencing digital
      alienation" dealing with loss of freedom when technology invades the private
      sphere; and "Missing the human touch" preferring human interaction over digital
      contact. CONCLUSION: Vulnerable people with T2DM are unprepared for digital
      interventions for disease management. Experiencing diabetes distress may be an
      intermediate mechanism leading to nonadherence to digital interventions and the
      preference for human interaction in vulnerable people with T2DM. Future
      interventions could include a designated caregiver and an allocated buddy to
      provide support and assist uptake of digital interventions for diabetes
      management.

PMID- 29067270
TI  - Examining diabetes distress, medication adherence, diabetes self-care activities,
      diabetes-specific quality of life and health-related quality of life among type 2
      diabetes mellitus patients.
AB  - AIMS: Health-Related Quality of Life (HRQoL) has been increasing attention in
      health outcome studies. Factors that individually influence HRQoL, diabetes self
      care behaviors, and medication adherence have been widely investigated; however,
      most previous studies have not tested an integrated association between multiple
      health outcomes. The purpose of this study was to formulate a hypothetical
      structural equation model linking HRQoL, diabetes distress, diabetes self-care
      activities, medication adherence and diabetes-dependent QoL in patients with Type
      2 Diabetes Mellitus (T2DM). METHODS: A cross-sectional study design was employed,
      and 497 patients with T2DM were recruited from outpatient clinics in three public
      hospitals and one government clinic. The patients completed a series of
      questionnaires. The hypothetical model was tested using Structural Equation
      Modeling (SEM) analysis. RESULTS: The values of the multiple fit indices
      indicated that the proposed model provided a good fit to the data. SEM results
      showed that medication adherence (MMAS) had a significant direct effect on
      diabetes distress (PAID) (Beta = -0.20). The self-care activities (SDSCA)
      construct was significantly related to PAID (Beta = -0.24). SDSCA was found to
      have a significant relationship with HRQoL (SF-36) (Beta = 0.11). Additionally,
      diabetes distress had a significant effect (Beta = -0.11) on HRQoL of patients.
      Finally, ADDQoL had a significant effect on HRQoL (Beta = 0.12). CONCLUSIONS: The
      various health outcome indicators such as self-care behaviors, diabetes distress,
      medication adherence and diabetes-dependent QoL need to be considered in clinical
      practice for enhancing HRQoL in those patients.

PMID- 29067271
TI  - Development of a youth-report measure of DPN symptoms: Conceptualization and
      content validation.
AB  - AIMS: To develop a content valid youth-report measure of diabetic peripheral
      neuropathy (DPN) symptoms. METHODS: Semi-structured interviews with 5 clinicians
      and 15 youth aged 8-17 with diabetes were conducted to elicit and clarify youth's
      DPN experiences. A systematic review of existing adult-report DPN symptom
      measures was conducted to identify item concepts representative of each
      experience. The concepts were transformed into items that were iteratively
      revised based on cognitive interviews (n = 13 youth aged 8-17) and readability
      analyses. RESULTS: Clinician and youth interviews supported a tripartite
      conceptual framework of youth DPN symptoms: paresthesia, pain, and anesthesia.
      Forty-eight youth-report items were generated to represent DPN symptoms
      identified through the semi-structured interviews and a systematic review of 13
      symptom questionnaires for adults. Of these, 23 were eliminated and 3 were
      revised based on cognitive interviews conducted with youth. The remaining 25
      items were on average, written at a 3rd grade reading level. CONCLUSIONS: This
      study is the first to generate a content valid self-report measure of youth's
      lived experiences with DPN that uses developmentally appropriate terminology.
      With further psychometric testing, the measure could be used to advance research
      on pediatric DPN and enhance clinicians' capacity to identify the condition in
      childhood.

PMID- 29067272
TI  - Prevalence of diabetic retinopathy and its relationship with glomerular
      filtration rate and other risk factors in patients with type 2 diabetes mellitus
      in Spain. DM2 HOPE study.
AB  - AIM: Diabetic retinopathy (DR) is the leading cause of blindness in working age
      population in developed countries. Albuminuria and estimated glomerular
      filtration rate (eGFR) have been considered biomarkers for DR. This study aimed
      to investigate the prevalence of DR and its relationship with eGFR and other risk
      factors in type 2 diabetic patients (T2DM) in Spain. METHODS: A cross-sectional
      and descriptive study has been performed in 14,266 patients. Clinical records
      were reviewed. Demographic data, clinical diagnoses, clinical variables, and
      results from laboratory tests were recorded. Prevalence rates of DR were
      calculated. Logistic regression analysis was applied to assess predictors of the
      DR presence/absence. RESULTS: DR prevalence was 14.9%, being more prevalent in
      women (p = 0.0087) and in older patients (p < 0.0001). Duration of disease (OR =
      5.3, IC95% = 3.8-7.4; p < 0.0001), eGFR < 60 ml/min/1.73 m2 (OR = 2.0, IC95% 1.6
      2.4; p < 0.0001), levels of HbA1c >= 7% (OR = 1.9, IC95% = 1.5-2.3; p < 0.0001)
      and high blood pressure (OR = 1.6, IC95% = 1.2-2.1; p = 0.0032) were associated
      with higher risk of DR. DR was also more frequent in patients taking insulin
      (32,6% vs. 10,2%; p < 0.0001). CONCLUSION: Around one in seven patients with T2DM
      has DR after nine years since diagnosis. Time since diagnosis, insulin therapy,
      cardiovascular profile, and renal dysfunction are associated with DR in patients
      with T2DM in Spain.

PMID- 29067273
TI  - Translating diabetes research from multiple directions - microvascular to
      psychosocial.

PMID- 29067274
TI  - Further the liquid biopsy: Gathering pieces of the puzzle of genometastasis
      theory.
AB  - Metastasis is the major cause of mortality in cancer disease and still
      constitutes one of the most controversial mechanism, not yet fully understood.
      What is almost beyond doubt is that circulatory system is crucial for cancer
      propagation. Regarding this system, much attention has been recently paid to
      liquid biopsy. This technique is aimed to detect circulating tumor cells (CTCs)
      and circulating nucleic acids so it can be used as a tool for diagnostic,
      prognostic and follow-up of patients. Whereas CTCs tend to be scarce in serum and
      plasma from cancer patient, abundant circulating nucleic acids can be detected in
      the same location. This fact, together with the genetic origin of cancer, stands
      out the relevance of circulating nucleic acids and shed light into the role of
      nucleic acids as drivers of metastasis, a recently discovered phenomenon called
      Genometastasis. This innovative theory supports the transfer of oncogenes from
      cancer cells to normal and susceptible cells located in distant target organs
      through circulatory system. What is more, many biological processes haven been
      described to deliver and secrete circulating nucleic acids into the circulation
      which can allow such horizontal transfer of oncogenes. In this review, we focus
      not only on these mechanisms but also we demonstrate its putative role in cancer
      propagation and give insights about possible therapeutic strategies based on this
      theory. Our objective is to demonstrate how findings about cell-to-cell
      communications and previous results can agree with this unprecedented theory.

PMID- 29067276
TI  - Characteristics of Clostridium difficile infection in patients hospitalized with
      myelodysplastic syndrome or acute myelogenous leukemia.
AB  - AIM: To evaluate factors associated with Clostridium difficile infection (CDI)
      and outcomes of CDI in the myelodysplastic syndrome (MDS) and acute myeloid
      leukemia (AML) population. METHODS: After IRB approval, all MDS/AML patients
      hospitalized at the University of Maryland Greenebaum Comprehensive Cancer Center
      between August 2011 and December 2013 were identified. Medical charts were
      reviewed for demographics, clinical information, development of CDI,
      complications of CDI, and mortality. Patients with CDI, defined as having a
      positive stool PCR done for clinical suspicion of CDI, were compared to those
      without CDI in order to identify predictors of disease. A t-test was used for
      comparison of continuous variables and chi-square or Fisher's exact tests were
      used for categorical variables, as appropriate. RESULTS: Two hundred and twenty
      three patients (60.1% male, mean age 61.3 years, 13% MDS, 87% AML) had 594 unique
      hospitalizations during the study period. Thirty-four patients (15.2%) were
      diagnosed with CDI. Factors significantly associated with CDI included lower
      albumin at time of hospitalization (P < 0.0001), prior diagnosis of CDI (P <
      0.0001), receipt of cytarabine-based chemotherapy (P = 0.015), total days of
      neutropenia (P = 0.014), and total days of hospitalization (P = 0.005). Gender (P
      = 0.10), age (P = 0.77), proton-pump inhibitor use (P = 0.73), receipt of
      antibiotics (P = 0.66), and receipt of DNA hypomethylating agent-based
      chemotherapy (P = 0.92) were not significantly associated with CDI. CONCLUSION:
      CDI is common in the MDS/AML population. Factors significantly associated with
      CDI in this population include low albumin, prior CDI, use of cytarabine-based
      chemotherapy, and prolonged neutropenia. In this study, we have identified a
      subset of patients in which prophylaxis studies could be targeted.

PMID- 29067277
TI  - Factors influencing response to ingenol mebutate therapy for actinic keratosis of
      face and scalp.
AB  - AIM: To determine factors independently influencing response to ingenol mebutate
      therapy and assess efficacy on clinical setting of non-hypertrophic non
      hyperkeratotic actinic keratosis (AK). METHODS: Consecutive patients affected by
      non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to
      receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3
      consecutive days. Local skin reactions were calculated at each follow up visit
      using a validated composite score. Efficacy was evaluated by the comparison of
      clinical and dermoscopic pictures before the treatment and at day 57, and
      classified as complete, partial and poor response. RESULTS: A number of 130
      patients were enrolled, of which 101 (77.7%) were treated on the face, while 29
      (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%)
      reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%)
      achieved a complete response while 61 (46.9%) a partial one. Logistic backward
      multivariate analysis showed that facial localization, level of local skin
      reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were
      factors independently associated with the achievement of a complete response.
      CONCLUSION: Ingenol mebutate 0.015% gel, when properly applied, is more effective
      on the face than on the scalp and efficacy is directly associated to LSR score.

PMID- 29067278
TI  - Prophylactic lateral pelvic lymph node dissection in stage IV low rectal cancer.
AB  - AIM: To assess the clinical significance of prophylactic lateral pelvic lymph
      node dissection (LPLND) in stage IV low rectal cancer. METHODS: We selected 71
      consecutive stage IV low rectal cancer patients who underwent primary tumor
      resection, and enrolled 50 of these 71 patients without clinical LPLN metastasis.
      The patients had distant metastasis such as liver, lung, peritoneum, and
      paraaortic LN. Clinical LPLN metastasis was defined as LN with a maximum diameter
      of 10 mm or more on preoperative pelvic computed tomography scan. All patients
      underwent primary tumor resection, 27 patients underwent total mesorectal
      excision (TME) with LPLND (LPLND group), and 23 patients underwent only TME (TME
      group). Bilateral LPLND was performed simultaneously with primary tumor resection
      in LPLND group. R0 resection of both primary and metastatic sites was achieved in
      20 of 50 patients. We evaluated possible prognostic factors for 5-year overall
      survival (OS), and compared 5-year cumulative local recurrence between the LPLND
      and TME groups. RESULTS: For OS, univariate analyses revealed no significant
      benefit in the LPLND compared with the TME group (28.7% vs 17.0%, P = 0.523);
      multivariate analysis revealed that R0 resection was an independent prognostic
      factor. Regarding cumulative local recurrence, the LPLND group showed no
      significant benefit compared with TME group (21.4% vs 14.8%, P = 0.833).
      CONCLUSION: Prophylactic LPLND shows no oncological benefits in patients with
      Stage IV low rectal cancer without clinical LPLN metastasis.

PMID- 29067275
TI  - Stereotactic radiotherapy for prostate cancer: A review and future directions.
AB  - Prostate cancer affects over 200000 men annually in the United States alone. The
      role of conventionally fractionated external beam radiation therapy (RT) is well
      established as a treatment option for eligible prostate cancer patients; however,
      the use of stereotactic body radiotherapy (SBRT) in this setting is less well
      defined. Within the past decade, there have been a number of studies
      investigating the feasibility of SBRT as a potential treatment option for
      prostate cancer patients. SBRT has been well studied in other disease sites, and
      the shortened treatment course would allow for greater convenience for patients.
      There may also be implications for toxicity as well as disease control. In this
      review we present a number of prospective and retrospective trials of SBRT in the
      treatment of prostate cancer. We focus on factors such as biochemical progression
      free survival, prostate specific antigen (PSA) response, and toxicity in order to
      compare SBRT to established treatment modalities. We also discuss future steps
      that the clinical community can take to further explore this new treatment
      approach. We conclude that initial studies examining the use of SBRT in the
      treatment of prostate cancer have demonstrated impressive rates of biochemical
      recurrence-free survival and PSA response, while maintaining a relatively
      favorable acute toxicity profile, though long-term follow-up is needed.

PMID- 29067279
TI  - First report of small cell lung cancer with PTHrP-induced hypercalcemic
      pancreatitis causing disconnected duct syndrome.
AB  - Here we report a patient diagnosed with small cell lung cancer after first
      presenting with parathyroid hormone-related peptide-induced hypercalcemic
      pancreatitis and developed walled-off necrosis that resulted in disruption of the
      main pancreatic duct. Disconnected duct syndrome (DDS) is a rare syndrome that
      occurs when the main pancreatic duct exocrine flow is disrupted resulting in
      leakage of pancreatic enzymes and further inflammatory sequela. To date, no prior
      reports have described DDS occurring with paraneoplastic reactions. Diagnostic
      imaging techniques and therapeutic interventions are reviewed to provide insight
      into current approaches to DDS.

PMID- 29067280
TI  - Charcot-Marie-Tooth hereditary neuropathy revealed after administration of
      docetaxel in advanced breast cancer.
AB  - Charcot-Marie-Tooth (CMT) neuropathy is the most common hereditary cause of
      neuropathy. Diagnosis is usually not made during the childhood but in adolescence
      or late adulthood. It is reported in the literature that some neurotoxic
      chemotherapeutical agents can reveal an asymptomatic CMT IA hereditary
      neuropathy. To our knowledge, we report here the first case of CMT IA revealed in
      a 55-year-old woman after the administration of docetaxel/trastuzumab/pertuzumab
      for metastatic breast cancer. This case stresses again the necessity to obtain a
      complete personal and familial anamnesis and to perform a neurologic examination
      before the administration of neurotoxic chemotherapeutical agents to prevent the
      clinical expression of these hereditary neuropathies.

PMID- 29067281
TI  - Corrigendum: Correction to the author's affiliation.
AB  - [This corrects the article on p. 21 in vol. 47, PMID: 28127536.][This corrects
      the article on p. 242 in vol. 46, PMID: 27478801.].

PMID- 29067282
TI  - Characterization of the Growth of Chlamydia trachomatis in In Vitro-Generated
      Stratified Epithelium.
AB  - Chlamydia infection targets the mucosal epithelium, where squamous and columnar
      epithelia can be found. Research on Chlamydia-epithelia interaction has
      predominantly focused on columnar epithelia, with very little known on how
      Chlamydia interacts with the squamous epithelium. The stratification and
      differentiation processes found in the squamous epithelium might influence
      chlamydial growth and infection dissemination. For this reason, three-dimensional
      (3D) organotypic stratified squamous epithelial cultures were adapted to mimic
      the stratified squamous epithelium and chlamydial infection was characterized.
      Chlamydia trachomatis infection in monolayers and 3D cultures were monitored by
      immunofluorescence and transmission electron microscopy to evaluate inclusion
      growth and chlamydial interconversion between elementary and reticulate body. We
      observed that the stratified epithelium varied in susceptibility to C.
      trachomatis serovars L2 and D infection. The undifferentiated basal cells were
      susceptible to infection by both serovars, while the terminally differentiated
      upper layers were resistant. The differentiating suprabasal cells exhibited
      different susceptibilities to serovars L2 and D, with the latter unable to
      establish a successful infection in this layer. Mature elementary body-containing
      inclusions were much more prevalent in these permissive basal layers, while the
      uppermost differentiated layers consistently harbored very few reticulate bodies
      with no elementary bodies, indicative of severely limited bacterial replication
      and development. For serovar D, the differentiation state of the host cell was a
      determining factor, as calcium-induced differentiation of cells in a monolayer
      negatively affected growth of this serovar, in contrast to serovar L2. The
      apparent completion of the developmental cycle in the basal layers of the 3D
      cultures correlated with the greater degree of dissemination within and the level
      of disruption of the stratified epithelium. Our studies indicate that the
      squamous epithelium is a suboptimal environment for growth, and thus potentially
      contributing to the protection of the lower genital tract from infection. The
      relatively more fastidious serovar D exhibited more limited growth than the
      faster-growing and more invasive L2 strain. However, if given access to the more
      hospitable basal cell layer, both strains were able to produce mature inclusions,
      replicate, and complete their developmental cycle.

PMID- 29067283
TI  - Small Molecule Mediated Restoration of Mitochondrial Function Augments Anti
      Mycobacterial Activity of Human Macrophages Subjected to Cholesterol Induced
      Asymptomatic Dyslipidemia.
AB  - Mycobacterium tuberculosis (M.tb) infection manifests into tuberculosis (TB) in a
      small fraction of the infected population that comprises the TB susceptible
      group. Identifying the factors potentiating susceptibility to TB persistence is
      one of the prime agenda of TB control programs. Recently, WHO recognized diabetes
      as a risk factor for TB disease progression. The closely related pathological
      state of metabolic imbalance, dyslipidemia, is yet another emerging risk factor
      involving deregulation in host immune responses. While high cholesterol levels
      are clinically proven condition for perturbations in cardiac health, a
      significant fraction of population these days suffer from borderline risk
      cholesterol profiles. This apparently healthy population is susceptible to
      various health risks placing them in the "pre-disease" range. Our study focuses
      on determining the role of such asymptomatic dyslipidemia as a potential risk
      factor for susceptibility to TB persistence. Macrophages exposed to sub
      pathological levels of cholesterol for chronic period, besides impaired release
      of TNF-alpha, could not clear intracellular pathogenic mycobacteria effectively
      as compared to the unexposed cells. These cells also allowed persistence of
      opportunistic mycobacterial infection by M. avium and M. bovis BCG, indicating
      highly compromised immune response. The cholesterol-treated macrophages developed
      a foamy phenotype with a significant increase in intracellular lipid-bodies prior
      to M.tb infection, potentially contributing to pre-disease state for tuberculosis
      infection. The foamy phenotype, known to support M.tb infection, increased
      several fold upon infection in these cells. Additionally, mitochondrial
      morphology and function were perturbed, more so during infection in cholesterol
      treated cells. Pharmacological supplementation with small molecule M1 that
      restored mitochondrial structural and functional integrity limited M.tb survival
      more effectively in cholesterol exposed macrophages. Mechanistically, M1 molecule
      promoted clearance of mycobacteria by reducing total cellular lipid content and
      restoring mitochondrial morphology and function to its steady state. We further
      supported our observations by infection assays in PBMC-derived macrophages from
      clinically healthy volunteers with borderline risk cholesterol profiles. With
      these observations, we propose that prolonged exposure to sub-pathological
      cholesterol can lead to asymptomatic susceptibility to M.tb persistence. Use of
      small molecules like M1 sets yet another strategy for host-directed therapy where
      re-functioning of mitochondria in cholesterol abused macrophages can improve M.tb
      clearance.

PMID- 29067285
TI  - Decreasing Total Medication Exposure and Length of Stay While Completing
      Withdrawal for Neonatal Abstinence Syndrome during the Neonatal Hospital Stay.
AB  - INTRODUCTION: Neonatal abstinence syndrome (NAS) is a rapidly growing public
      health concern that has considerably increased health-care utilization and health
      care costs. In an effort to curtail costs, attempts have been made to complete
      withdrawal as an outpatient. Outpatient therapy has been shown to prolong
      exposure to medications, which may negatively impact neurodevelopmental and
      behavioral outcomes. We hypothesized that the implementation of a modified NAS
      protocol would decrease total drug exposure and length of stay while allowing for
      complete acute drug withdrawal during the neonatal hospital stay. METHODS: Data
      were derived retrospectively from medical records of term (>=37 0/7) infants with
      NAS who were treated with pharmacologic therapy in the University of Louisville
      Hospital Neonatal Intensive Care Unit from 2005 to 2015. The pharmacologic
      protocol (SP1) for infants treated between 2005 and March 2014 (n = 146) dosed
      oral morphine every 4 h and utilized phenobarbital as adjuvant therapy. Protocol
      2 (SP2) initiated after March 2014 (n = 44) dosed morphine every 3 h and used
      clonidine as adjuvant therapy. Charts were reviewed for demographic information
      and maternal drug history. Maternal and infant toxicology screens were recorded.
      The length of morphine therapy and need for adjuvant drug therapy were noted.
      Length of stay was derived from admission and discharge dates. RESULTS: The
      length of morphine therapy was decreased by 8.5 days from 35 to 26.5 days (95% CI
      4.5-12 days) for infants treated with SP2 vs. SP1 (p < 0.001). The need for
      adjuvant pharmacologic therapy was decreased by 24% in patients treated with SP2
      vs. SP1 (p = 0.004). The length of stay was decreased by 9 days from 42 to 33
      days (95% CI 5.1-13 days) for infants treated with SP2 vs. SP1 (p < 0.001). The
      decreased length of stay resulted in an average reduction of hospital charges by
      $27,090 per patient in adjusted 2015 US Dollars. CONCLUSION: This study
      demonstrates that total drug exposure and length of stay can be reduced while
      successfully completing acute withdrawal during the neonatal hospital stay.

PMID- 29067284
TI  - Clinical features, predictive correlates, and pathophysiology of immune-related
      adverse events in immune checkpoint inhibitor treatments in cancer: a short
      review.
AB  - Identification and characterization of T-cell regulatory mechanisms, or
      checkpoints, have led to a wave of drug development aimed at inhibiting these
      targets to "remove the brakes" of the immune system. This class of anticancer
      therapeutics, termed immune checkpoint inhibitors (ICIs), has harnessed the
      potential of the body's own immune system to recognize cancerous cells and
      selectively eliminate them, in some cases with alarming success. This new
      breakthrough, however, has not been without its drawbacks. Immune-related adverse
      events (irAEs) are adverse events encountered during treatment with ICIs that are
      thought to be mediated through the patient's immune system which can manifest
      with a variety of symptoms which often resemble autoimmunity. These events range
      widely in presentation and severity and are reported frequently. Here, we will
      discuss a large selection of case reports in order to inform the clinician,
      laboratorian, and researcher of the scope of organ systems affected, the severity
      of the conditions being encountered, and the responses of these events to
      treatment, as well as explore the use of ICIs in the setting of preexisting
      autoimmunity. We will also consider the ability to detect autoantibodies before
      and during irAEs as well as the correlations that irAEs have with clinical
      outcomes. Finally, we will conclude by exploring the possibility that two
      distinct pathways may be contributing to the phenomenon of irAEs within this
      class of drugs, and the role that this might play in future research and clinical
      practice.

PMID- 29067286
TI  - Recognition of a Virtual Scene via Simulated Prosthetic Vision.
AB  - In order to effectively aid the blind with optimal low-resolution vision and
      visual recovery training, pathfinding and recognition tests were performed using
      a simulated visual prosthetic scene. Simple and complex virtual scenes were built
      using 3DMAX and Unity, and pixelated to three different resolutions (32 * 32, 64
      * 64, and 128 * 128) for real-time pixel processing. Twenty subjects were
      recruited to complete the pathfinding and object recognition tasks within the
      scene. The recognition accuracy and time required were recorded and analyzed
      after the trials. In the simple simulated prosthetic vision (SPV) scene, when the
      resolution was increased from 32 * 32 to 48 * 48, the object recognition time
      decreased from 92.19 +/- 6.97 to 43.05 +/- 6.08 s, and the recognition accuracy
      increased from 51.22 +/- 8.53 to 85.52 +/- 4.93%. Furthermore, the number of
      collisions decreased from 10.00 +/- 2.31 to 3.00 +/- 0.68. When the resolution
      was increased from 48 * 48 to 64 * 64, the object recognition time further
      decreased from 43.05 +/- 6.08 to 19.46 +/- 3.71 s, the recognition accuracy
      increased from 85.52 +/- 4.93 to 96.89 +/- 2.06%, and the number of collisions
      decreased from 3.00 +/- 0.68 to 1.00 +/- 0.29. In complex scenes, the time
      required to recognize the room type decreased from 115.00 +/- 23.02 to 68.25 +/-
      17.23 s, and object recognition accuracy increased from 65.69 +/- 9.61 to 80.42
      +/- 7.70% when the resolution increased from 48 * 48 to 64 * 64. When the
      resolution increased from 64 * 64 to 128 * 128, the time required to recognize
      the room type decreased from 68.25 +/- 17.23 to 44.88 +/- 9.94 s, and object
      recognition accuracy increased from 80.42 +/- 7.71 to 85.69 +/- 7.39%. Therefore,
      one can conclude that there are correlations between pathfinding and recognition.
      When the resolution increased, the time required for recognition decreased, the
      recognition accuracy increased, and the number of collisions decreased. Although
      the subjects could partially complete the recognition task at a resolution of 32
      * 32, the recognition time was too long and recognition accuracy was not good
      enough to identify simple scenes. Complex scenes required a resolution of at
      least 48 * 48 for complete recognition. In addition, increasing the resolution
      shortened the time required to identify the type of room, and improved the
      recognition accuracy.

PMID- 29067287
TI  - Holmium Laser Lithotripsy in the New Stone Age: Dust or Bust?
AB  - Modern day holmium laser systems for ureteroscopy (URS) provide users with a
      range of settings, namely pulse energy (PE), pulse frequency (Fr), and pulse
      width (PW). These variables allow the surgeon to choose different combinations
      that have specific effects on stone fragmentation during URS lithotripsy. Contact
      laser lithotripsy can be performed using fragmentation or dusting settings.
      Fragmentation employs settings of low Fr and high PE to break stones that are
      then extracted with retrieval devices. Dusting is the utilization of high Fr and
      low PE settings to break stones into submillimeter fragments for spontaneous
      passage without the need for basket retrieval. Use of the long PW mode during
      lithotripsy can reduce stone retropulsion and is increasingly available in new
      generation lasers. During non-contact laser lithotripsy, stone fragments are
      rapidly pulverized in a calyx in laser bursts that result in stones breaking into
      fine fragments. In this review, we discuss the effect of different holmium laser
      settings on stone fragmentation, and the clinical implications in a very much
      evolving field.

PMID- 29067288
TI  - Gene Therapy Using Plasmid DNA Encoding Vascular Endothelial Growth Factor 164
      and Fibroblast Growth Factor 2 Genes for the Treatment of Horse Tendinitis and
      Desmitis: Case Reports.
AB  - In this clinical study, for the first time we used the direct gene therapy to
      restore severe injuries of the suspensory ligament branch and superficial digital
      flexor tendon in horses (Equus caballus). We injected the plasmid DNA encoding
      two therapeutic species-specific growth factors: vascular endothelial growth
      factor 164 and fibroblast growth factor 2 at the site of injury in the suspensory
      ligament branch and tendon. Treatment effects were evaluated with the use of
      clinical observation and ultrasound imaging during a period of a few months. We
      showed that gene therapy used within a period of 2-3 months after the injury
      resulted in the complete recovery of functions and full restoration of the
      severely damaged suspensory ligament and superficial digital flexor tendon.

PMID- 29067289
TI  - Racial Differences in Neighborhood Perceptions and their Influences on Physical
      Activity among Urban Older Women.
AB  - BACKGROUND: Proper levels of physical activity (PA) are important to healthy
      aging. Little is known about racial differences in influences of neighborhood
      perceptions (NP) on PA and use of neighborhood resources among community-dwelling
      older women. MATERIALS AND METHODS: In 2014 and 2015, 49 white and 44 black women
      of age 65 and older living in Washington, DC were queried about their PA, NP, use
      of neighborhood resources and sociodemographic characteristics. They wore an
      accelerometer and a Global Positioning System device concurrently for 7
      consecutive days. Data were analyzed by race. RESULTS: Compared to Whites, Blacks
      had lower NP scores (71% positive vs. 77%, p = 0.01), lower mean daily step
      counts (mean (SD): 3256 (1918) vs. 5457 (2989), p < 0.001), and lower frequencies
      of all exercise activities combined (19.7 (8.7) vs. 25.2 (11.8) per week, p =
      0.01). For both Whites and Blacks, better NPs were associated with more frequent
      PA both at (p = 0.05) and away from home (p = 0.01). However, better NPs were
      associated with higher frequencies of exercise activities, moderate-to-high
      intensity activities, and utilitarian walking for Whites but not Blacks (p < 0.05
      for race-perception interaction terms). CONCLUSIONS: In an urban setting, older
      Black women were more likely than older White women to have poor NPs, less PA,
      and weaker or no association of positive NPs with higher levels of certain PAs.
      Such substantial racial differences warrant further investigation and
      consideration in health promotion programs.

PMID- 29067290
TI  - Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a
      putative disease-modifying monoclonal antibody for the treatment of Alzheimer's
      disease.
AB  - INTRODUCTION: Recent failures in phase 3 clinical trials in Alzheimer's disease
      (AD) suggest that novel approaches to drug development are urgently needed. Phase
      3 risk can be mitigated by ensuring that clinical efficacy is established before
      initiating confirmatory trials, but traditional phase 2 trials in AD can be
      lengthy and costly. METHODS: We designed a Bayesian adaptive phase 2, proof-of
      concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody
      targeting amyloid protofibrils. The study design used dose response and
      longitudinal modeling. Simulations were used to refine study design features to
      achieve optimal operating characteristics. RESULTS: The study design includes
      five active treatment arms plus placebo, a clinical outcome, 12-month primary
      endpoint, and a maximum sample size of 800. The average overall probability of
      success is >=80% when at least one dose shows a treatment effect that would be
      considered clinically meaningful. Using frequent interim analyses, the
      randomization ratios are adapted based on the clinical endpoint, and the trial
      can be stopped for success or futility before full enrollment. DISCUSSION:
      Bayesian statistics can enhance the efficiency of analyzing the study data. The
      adaptive randomization generates more data on doses that appear to be more
      efficacious, which can improve dose selection for phase 3. The interim analyses
      permit stopping as soon as a predefined signal is detected, which can accelerate
      decision making. Both features can reduce the size and duration of the trial.
      This study design can mitigate some of the risks associated with advancing to
      phase 3 in the absence of data demonstrating clinical efficacy. Limitations to
      the approach are discussed.

PMID- 29067292
TI  - How can we really improve screening methods for AD prevention trials?

PMID- 29067291
TI  - First in human study with a prodrug of galantamine: Improved benefit-risk ratio?
AB  - INTRODUCTION: Gln-1062 (Memogain) is a pharmacologically inactive prodrug of
      galantamine. Owing to its lipophilic nature, it preferentially enters the brain,
      where it is cleaved into active galantamine. Gln-1062 is expected to have fewer
      peripheral side effects than other cholinesterase inhibitors, with improved
      effectiveness. METHODS: This was a double-blind, comparator and placebo
      controlled, sequential cohort, single ascending dose study in 58 healthy subjects
      with Gln-1062 in doses of 5.5, 11, 22, 33, and 44 mg, compared with oral
      galantamine 16 mg and donepezil 10 mg. Safety, tolerability, pharmacokinetics,
      and pharmacodynamics were assessed. RESULTS: Gln-1062 doses up to 33 mg were well
      tolerated and induced a dose-dependent increase in the plasma concentrations of
      Gln-1062 and galantamine. Gln-1062 had a dose-dependent positive effect on verbal
      memory and attention, mainly in the first hours after drug administration.
      DISCUSSION: Gln-1062 was better tolerated than galantamine in doses with the same
      molarity and led to improved effects in cognitive tests. This is most likely
      caused by the more favorable distribution ratio between peripheral and central
      cholinesterase inhibition. These results give reason for further exploration of
      this compound.

PMID- 29067293
TI  - Considerations for the assessment of suicidal ideation and behavior in older
      adults with cognitive decline and dementia.
AB  - INTRODUCTION: Better understanding of suicide risk and its management in older
      adults with cognitive impairment and/or dementia remain significant unmet public
      health needs. Urgency to address them derives from concern that CNS treatments
      for dementia may impact suicide risk. Regulatory guidances requiring assessment
      of emergent suicidal ideation and behavior (SI/SB) at every clinical trial visit
      emphasize the need for understanding their prevalence. METHODS: The literature
      regarding SI/SB in older persons with cognitive impairment or dementia was
      reviewed by an Alzheimer's Association Taskforce with emphasis on epidemiology,
      classification, assessment, and regulatory requirements. RESULTS: Gaps in our
      knowledge were identified, challenges discussed and recommendations for future
      work provided. DISCUSSION: Currently available SI/SB data from geriatric persons
      with dementia do not provide adequate understanding of its epidemiology,
      identification, assessment, or management. The growing public health burden of
      this population requires greater attention from clinicians and researchers on
      tactics and assessment tools to meet these needs.

PMID- 29067294
TI  - Suicidal ideation and behavior assessment in dementia studies: An Internet
      survey.
AB  - INTRODUCTION: The AARR task force on suicidal ideation and behavior (SI/SB) in
      dementia conducted an online survey on the extent of SI/SB in individuals
      diagnosed with mild cognitive impairment (MCI) or dementia who were participating
      in clinical trials. METHODS: Investigators with experience in conducting SI/SB
      assessments in clinical trial subjects with MCI or dementia were invited to
      complete a global 19-item online survey. RESULTS: A total of 204 evaluable
      responses were collected with the majority from North America and Europe (83.4%)
      and the remainder from Asia, Latin America, and Mideast/Africa. The mean (SD)
      number of subjects personally assessed by the respondents in the past year with
      MCI, mild-moderate dementia, or severe dementia was 12.8 (26.2), 31.2 (39.6), and
      10.1 (34.7), respectively. The mean number of subjects in each diagnostic group
      with suicidal ideation (SI), suicidal behavior (SB), or completed suicide (CS)
      was on average quite low (0.3 to 1.1 for SI, 0.1 to 0.2 for SB, and 0.0 to 0.2
      for CS). Confidence in subject self-reports of SI/SB over different time periods
      declined with increasing severity of cognitive impairment and with increasing
      duration of the recall time period assessed. Of respondents, 56% and 75% had low
      confidence in self-ratings of SI/SB from subjects with severe dementia over the
      past 24 hours and the past week to 1 month, respectively. Ratings of the
      reliability of information collected on SI/SB also decreased with increasing
      severity of cognitive impairment. Approximately 70% of respondents rated the
      reliability of the information they obtained from all sources (patient,
      caregiver, and others) for subjects with MCI as high, but only about half (42.0%
      to 55.3%) and less than a quarter (17.4% to 24.3%) rated the reliability of
      information obtained for subjects with mild to moderate dementia or severe
      dementia as high, respectively. DISCUSSION: These results support the usefulness
      of prospective SI/SB assessments in MCI and mild dementia, raise questions about
      the reliability of assessments in moderate dementia, and confirm their lack of
      clinical utility in severe dementia. The results highlight the need for
      development of validated assessment instruments adapted to the stage of cognitive
      decline of the patients under study and may be the most effective in the earliest
      stages of the disease.

PMID- 29067296
TI  - Assessing reliability of short and tick box forms of the ANU-ADRI: Convenient
      alternatives of a self-report Alzheimer's disease risk assessment.
AB  - INTRODUCTION: To assess the reliability of short versions of the Australian
      National University Alzheimer's Disease Risk Index (ANU-ADRI). METHODS: A short
      form of the ANU-ADRI (ANU-ADRI-SF) was developed by assessing risk and protective
      factors with single questions where possible and with short forms of sub
      questionnaires where available. The tick box form of the ANU-ADRI (ANU-ADRI-TB)
      was developed with unique questions for each risk and protective factor for
      Alzheimer's disease. The short versions were evaluated in an independent
      community sample of 504 participants with a mean age of 45.01 (SD = 14.85, range
      = 18-81). RESULTS: The short versions demonstrated high reliabilities when
      compared with the ANU-ADRI. However, the proportion of misclassification was high
      for some risk factors and particularly for the ANU-ADRI-TB. DISCUSSION: The ANU
      ADRI-SF may be considered if less reliable questions from the ANU-ADRI-SF can be
      replaced with more reliable questions from the ANU-ADRI for risk/protective
      factors with high misclassification.

PMID- 29067295
TI  - The ALFA project: A research platform to identify early pathophysiological
      features of Alzheimer's disease.
AB  - INTRODUCTION: The preclinical phase of Alzheimer's disease (AD) is optimal for
      identifying early pathophysiological events and developing prevention programs,
      which are shared aims of the ALFA project, including the ALFA registry and parent
      cohort and the nested ALFA+ cohort study. METHODS: The ALFA parent cohort
      baseline visit included full cognitive evaluation, lifestyle habits
      questionnaires, DNA extraction, and MRI. The nested ALFA+ study adds wet and
      imaging biomarkers for deeper phenotyping. RESULTS: A total of 2743 participants
      aged 45 to 74 years were included in the ALFA parent cohort. We show that this
      cohort, mostly composed of cognitively normal offspring of AD patients, is
      enriched for AD genetic risk factors. DISCUSSION: The ALFA project represents a
      valuable infrastructure that will leverage with different studies and trials to
      prevent AD. The longitudinal ALFA+ cohort will serve to untangle the natural
      history of the disease and to model the preclinical stages to develop successful
      trials.

PMID- 29067298
TI  - A randomized controlled study to evaluate the effect of bexarotene on amyloid
      beta and apolipoprotein E metabolism in healthy subjects.
AB  - INTRODUCTION: We conducted a phase Ib proof of mechanism trial to determine
      whether bexarotene (Targretin) increases central nervous system (CNS)
      apolipoprotein E (apoE) levels and alters Abeta metabolism in normal healthy
      individuals with the APOE epsilon3/epsilon3 genotype. METHODS: We used stable
      isotope labeling kinetics (SILK-ApoE and SILK-Abeta) to measure the effect of
      bexarotene on the turnover rate of apoE and Abeta peptides and stable isotope
      spike absolute quantitation (SISAQ) to quantitate their concentrations in the
      cerebrospinal fluid (CSF). Normal subjects were treated for 3 days with
      bexarotene (n = 3 women, 3 men, average 32 years old) or placebo (n = 6 women,
      average 30.2 years old) before administration of C13-leucine and collection of
      plasma and CSF over the next 48 hours. Bexarotene concentrations in plasma and
      CSF were also measured. RESULTS: Oral administration of bexarotene resulted in
      plasma levels of 1 to 2 MUM; however, only low nM levels were found in CSF.
      Bexarotene increased CSF apoE by 25% but had no effect on metabolism of Abeta
      peptides. DISCUSSION: Bexarotene has poor CNS penetration in normal human
      subjects. Drug treatment resulted in a modest increase in CSF apoE levels. The
      absence of an effect on Abeta metabolism is likely reflective of the low CNS
      levels of bexarotene achieved. This study documents the utility of SILK-ApoE
      technology in measuring apoE kinetics in humans. TRIAL REGISTRATION: This trial
      is registered at clinicaltrials.gov (NCT02061878).

PMID- 29067297
TI  - The roles of inflammation and immune mechanisms in Alzheimer's disease.
AB  - The Alzheimer's Association's Research roundtable met in April 2015 to explore
      the role of neuroinflammatory mechanisms in the progression of Alzheimer's
      disease (AD). The ability of innate immune cells, particularly microglia and
      astrocytes, to mediate neuroinflammation in AD has been implicated as a
      significant contributor to disease pathogenesis. Adaptive immunity, which plays
      an important role in responding to injury and some diseases of the central
      nervous system, may contribute to neuroinflammation in AD as well. Communication
      between the central and peripheral immune systems may also be important in AD. An
      increased understanding of the physiology of the innate immune system may aid the
      identification of new therapeutic targets or mechanisms. The development of
      predictive animal models and translatable neuroinflammation biomarkers for AD
      would also facilitate the advancement of novel treatments for innate immunity.
      Important challenges impeding the advancement of new therapeutic agents and
      strategies to overcome them were discussed.

PMID- 29067299
TI  - Haloperidol inactivates AMPK and reduces tau phosphorylation in a tau mouse model
      of Alzheimer's disease.
AB  - INTRODUCTION: The use of antipsychotic medications in Alzheimer's disease has
      been associated with an increased risk of mortality in clinical trials. However,
      an older postmortem literature suggests that those with schizophrenia treated in
      an era of exclusively conventional antipsychotic medications had a surprisingly
      low incidence of tau pathology. No previously published studies have investigated
      the impact of conventional antipsychotic exposure on tau outcomes in a tau mouse
      model of AD. METHODS: In two experiments, transgenic rTg (tauP301L) 4510 tau mice
      were treated with either haloperidol or vehicle and phosphotau epitopes were
      quantified using high-sensitivity tau ELISA. RESULTS: After treatments of 2 and 6
      week's duration, mice treated with haloperidol evidenced a significant reduction
      in tau phosphorylation associated with an inactivation of the tau kinase AMPK.
      DISCUSSION: The data suggest that D2 receptor blockade reduces tau
      phosphorylation in vivo. Future studies are necessary to investigate the impact
      of this reduction on tau neuropathology.

PMID- 29067300
TI  - Demonstration of safety of intravenous immunoglobulin in geriatric patients in a
      long-term, placebo-controlled study of Alzheimer's disease.
AB  - INTRODUCTION: We present safety results from a study of Gammagard Liquid
      intravenous immunoglobulin (IGIV) in patients with probable Alzheimer's disease.
      METHODS: This was a placebo-controlled double-blind study. Subjects were
      randomized to 400 mg/kg (n = 127), 200 mg/kg (n = 135) IGIV, or to 0.25% human
      albumin (n = 121) administered every 2 weeks +/- 7 days for 18 months. RESULTS:
      Elevated risk ratios of IGIV versus placebo included chills (3.85) in 9.5% of
      IGIV-treated subjects (all doses), compared to 2.5% of placebo-treated subjects,
      and rash (3.08) in 15.3% of IGIV-treated subjects versus 5.0% of subjects treated
      with placebo. Subjects in the highest IGIV dose group had the lowest proportion
      of SAEs considered related to product (2 of 127 [1.6%]). Subjects treated with
      IGIV experienced a lower rate of respiratory and all other infections compared to
      placebo. DISCUSSION: IGIV-treated subjects did not experience higher rates of
      renal failure, lung injury, or thrombotic events than the placebo group. There
      were no unexpected safety findings. IGIV was well tolerated throughout 18 months
      of treatment in subjects aged 50-89 years.

PMID- 29067302
TI  - B-vitamins are potentially a cost-effective population health strategy to tackle
      dementia: Too good to be true?
AB  - INTRODUCTION: To respond to the threat of dementia to public health and the
      economy, we need to prioritize research resources on strategies that would be the
      most effective. In relation to the prevention of dementia, this article considers
      whether lowering plasma homocysteine by B-vitamin supplementation is one of the
      top priority and cost-effective treatments. METHOD: A decision model was
      constructed to calculate the lifetime costs and quality-adjusted life years
      (QALYs) of providing B-vitamin treatment to people in the United Kingdom over 60
      years with high levels (>13 MUmol/L) of plasma homocysteine, which was compared
      to the lifetime costs and outcomes of not providing them with the treatment.
      RESULTS: Treatment with B-vitamins will save L60,021 per QALY gained and so is
      highly cost-effective. DISCUSSION: We anticipate that this provocative finding
      will be debated by scientists, clinicians, and policy makers and eventually be
      tested in future clinical trials.

PMID- 29067301
TI  - NPT088 reduces both amyloid-beta and tau pathologies in transgenic mice.
AB  - INTRODUCTION: Alzheimer's disease (AD) is characterized by appearance of both
      extracellular senile plaques and intracellular neurofibrillary tangles, comprised
      of aggregates of misfolded amyloid-beta (Abeta) and hyper-phosphorylated tau,
      respectively. In a previous study, we demonstrated that g3p, a capsid protein
      from bacteriophage M13, binds to and remodels misfolded aggregates of proteins
      that assume an amyloid conformation. We engineered a fusion protein ("NPT088")
      consisting of the active fragment of g3p and human-IgG1-Fc. METHODS: Aged Tg2576
      mice or rTg4510 mice received NPT088 weekly via IP injection. Cognitive and/or
      functional motor endpoints were monitored during dosing. Pathology was quantified
      biochemically and immunohistochemically. RESULTS: NPT088-lowered Abeta plaque and
      improved cognitive performance of aged Tg2576 mice. Moreover, NPT088 reduced
      phospho-tau pathology, reduced brain atrophy, and improved cognition in rTg4510
      mice. DISCUSSION: These observations establish NPT088 as a novel therapeutic
      approach and potential drug class that targets both Abeta and tau, the hallmark
      pathologies of AD.

PMID- 29067303
TI  - Poor cerebrovascular function is an early marker of cognitive decline in healthy
      postmenopausal women.
AB  - INTRODUCTION: Impairment of cerebrovascular function becomes evident after
      menopause. No study has yet explored relationships between deficits in
      cerebrovascular function, cognitive performance, and mood in postmenopausal
      women. METHOD: Cerebrovascular function was assessed in 80 healthy postmenopausal
      women by monitoring blood flow velocity (BFV) in the middle and posterior
      cerebral arteries using transcranial Doppler ultrasound at rest, following a
      hypercapnic challenge, and during performance of a cognitive test battery; the
      latter assessed domains of memory and executive functions. Various measures of
      mood (i.e., Profile of Mood States and Center for Epidemiological Studies
      Depression Scale) were also assessed. RESULTS: Cerebral artery elasticity and BFV
      responsiveness to cognitive tests (neurovascular coupling) correlated with
      cognitive performance but not with depressive symptoms or mood states. Mood
      deficits were related to poor cognitive performance. CONCLUSION: These results
      highlight the importance of adequate cerebral perfusion for optimized cognitive
      function in healthy postmenopausal women. Preventative strategies to attenuate
      accelerated cognitive decline should also consider restoring cerebrovascular
      function.

PMID- 29067304
TI  - First-in-human, double-blind, placebo-controlled, single-dose escalation study of
      aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease.
AB  - INTRODUCTION: Aducanumab (BIIB037), a human monoclonal antibody selective for
      aggregated forms of amyloid beta, is being investigated as a disease-modifying
      treatment for Alzheimer's disease (AD). METHODS: This randomized, double-blind,
      placebo-controlled single ascending-dose study investigated the safety,
      tolerability, and pharmacokinetics (PK) of aducanumab in patients with mild-to
      moderate AD. Eligible patients were sequentially randomized 6:2 to aducanumab
      (0.3, 1, 3, 10, 20, 30, and 60 mg/kg) or placebo. RESULTS: The primary outcome
      was safety and tolerability. Doses <=30 mg/kg were generally well tolerated with
      no severe or serious adverse events (SAEs). All three patients who received 60
      mg/kg aducanumab developed SAEs of symptomatic amyloid-related imaging
      abnormalities, which completely resolved by weeks 8-15. Aducanumab Cmax, AUC0
      last, and AUCinf increased in a dose-proportional manner. DISCUSSION: In this
      single-dose study, aducanumab demonstrated an acceptable safety and tolerability
      profile and linear PK at doses <=30 mg/kg (clinicaltrials.govNCT01397539).

PMID- 29067306
TI  - Quantile regression to characterize solanezumab effects in Alzheimer's disease
      trials.
AB  - INTRODUCTION: In two solanezumab trials for mild-to-moderate Alzheimer's disease
      (AD) dementia, 27% of patients had biomarker confirmation of amyloid status. Of
      these, approximately 25% of mild patients and approximately 10% of moderate
      patients were amyloid negative and, as a group, did not exhibit clinical
      progression typical of AD. This post-hoc analysis describes a statistical
      surrogate for amyloid status. METHODS: Quantile regression was used to examine
      solanezumab treatment effects at fixed percentiles of varying degrees of clinical
      progression, with lowest percentiles (minimal progression atypical of AD) and
      higher percentiles acting as surrogates for amyloid negativity or positivity,
      respectively. RESULTS: In mild patients, solanezumab treatment effect was greater
      in higher percentiles of progression and less in lowest percentiles (AD
      atypical). In moderate patients, solanezumab did not show effects across most
      percentiles. DISCUSSION: Results are compatible with design of the ongoing
      solanezumab EXPEDITION 3 trial that limits patients to those with mild AD
      dementia and evidence of amyloid pathology.

PMID- 29067305
TI  - Vitamin E family: Role in the pathogenesis and treatment of Alzheimer's disease.
AB  - INTRODUCTION: Vitamin E family, composed by tocopherols and tocotrienols, is a
      group of compounds with neuroprotective properties. The exact role in the
      pathogenesis and the benefit of vitamin E as treatment for Alzheimer's disease
      (AD) are still under debate. METHODS: A literature search in PubMed, Medline, and
      Cochrane databases has been carried out. All types of studies, from bench and
      animal models to clinical, were included. RESULTS: High plasma vitamin E levels
      are associated with better cognitive performance, even if clear evidence of their
      ability to prevent or delay cognitive decline in AD is still lacking. Each
      vitamin E form is functionally unique and shows specific biological functions.
      Tocotrienols seem to have superior antioxidant and anti-inflammatory properties
      compared with tocopherols. DISCUSSION: The benefit of vitamin E as a treatment
      for AD is still under debate, mainly because of the inconsistent findings from
      observational studies and the methodological limitations of clinical trials.

PMID- 29067307
TI  - Insufficient evidence for vitamin E in Alzheimer's disease.
AB  - Vitamin E has recently been suggested to slow down the progression of Alzheimer's
      disease. Current evidence is based on three studies in patients with Alzheimer's
      disease and one study in patients with mild cognitive impairment which all
      together included only 1756 patients. Importantly, two of these studies were
      negative, and the two other studies had severe methodological weaknesses that
      preclude more definite interpretation. Based on the notion from patients
      suffering from cerebrovascular diseases that vitamin E may induce serious side
      effects (i.e., hemorhagic stroke), vitamin E cannot be recommended for use in
      Alzheimer's patients.

PMID- 29067308
TI  - Profiling the dynamics of CSF and plasma Abeta reduction after treatment with JNJ
      54861911, a potent oral BACE inhibitor.
AB  - OBJECTIVES: Safety, tolerability, pharmacokinetics, and pharmacodynamics of a
      novel beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor,
      JNJ-54861911, were assessed after single and multiple dosing in healthy
      participants. METHODS: Two randomized, placebo-controlled, double-blind studies
      were performed using single and multiple ascending JNJ-54861911 doses (up to 14
      days) in young and elderly healthy participants. Regular blood samples and
      frequent CSF samples, up to 36 hours after last dose, were collected to assess
      the pharmacokinetic and pharmacodynamic (Abeta, sAPPalpha,beta,total levels)
      profiles of JNJ-54861911. RESULTS: JNJ-54861911 was well-tolerated, adverse
      events were uncommon and unrelated to JNJ-54861911. JNJ-54861911 showed dose
      proportional CSF and plasma pharmacokinetic profiles. Plasma- and CSF-Abeta and
      CSF-sAPPbeta were reduced in a dose-dependent manner. Abeta reductions (up to
      95%) outlasted exposure to JNJ-54861911. APOE epsilon4 carrier status and
      baseline Abeta levels did not influence Abeta/sAPPbeta reductions. CONCLUSION:
      JNJ-54861911, a potent brain-penetrant BACE1 inhibitor, achieved high and stable
      Abeta reductions after single and multiple dosing in healthy participants.

PMID- 29067309
TI  - Alzheimer's drug-development pipeline: 2016.
AB  - BACKGROUND: Alzheimer's disease (AD) is growing in frequency and new therapies
      are urgently needed. METHODS: We assessed clinicaltrials.gov (accessed 1-4-2016)
      to determine the number and characteristics of trials in phase I, phase II, and
      phase III for treatment of AD. RESULTS: There are currently 24 agents in 36
      trials in phase III of AD drug development. Seven of these 24 agents are
      symptomatic cognitive-enhancing compounds, and 17 are disease-modifying
      treatments (DMTs). Most DMTs address amyloid-related targets (76%). There are 45
      agents in phase II being assessed in 52 clinical trials. Phase II trials include
      30 DMTs, with 26 small molecules and 4 immunotherapies. There are 24 agents in
      the first phase of AD drug development. DISCUSSION: Amyloid is the principal
      target of late-stage development programs. There are relatively few agents in
      clinical trials for AD suggesting a need to amplify the drug discovery ecosystem.

PMID- 29067310
TI  - Design of the NL-ENIGMA study: Exploring the effect of Souvenaid on cerebral
      glucose metabolism in early Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease is associated with early synaptic loss.
      Specific nutrients are known to be rate limiting for synapse formation. Studies
      have shown that administering specific nutrients may improve memory function,
      possibly by increasing synapse formation. This Dutch study explores the Effect of
      a specific Nutritional Intervention on cerebral Glucose Metabolism in early
      Alzheimer's disease (NL-ENIGMA, Dutch Trial Register NTR4718,
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4718). The NL-ENIGMA
      study is designed to test whether the specific multinutrient combination Fortasyn
      Connect present in the medical food Souvenaid influences cerebral glucose
      metabolism as a marker for improved synapse function. METHODS: This study is a
      double-blind, randomized controlled parallel-group single-center trial. Forty
      drug-naive patients with mild cognitive impairment or mild dementia with evidence
      of amyloid deposition are 1:1 randomized to receive either the multinutrient
      combination or placebo once daily. Main exploratory outcome parameters include
      absolute quantitative positron emission tomography with 18F-fluorodeoxyglucose
      (including arterial sampling) and standard uptake value ratios normalized for the
      cerebellum or pons after 24 weeks. DISCUSSION: We expect the NL-ENIGMA study to
      provide further insight in the potential of this multinutrient combination to
      improve synapse function.

PMID- 29067311
TI  - Mnemonic strategy training of the elderly at risk for dementia enhances
      integration of information processing via cross-frequency coupling.
AB  - INTRODUCTION: We sought to identify whether intensive 10-week mobile health
      mnemonic strategy training (MST) could shift the resting-state brain network more
      toward cortical-level integration, which has recently been proven to reflect the
      reorganization of the brain networks compensating the cognitive decline. METHODS:
      One hundred fifty-eight patients with mild cognitive impairment (MCI) were
      selected and participated in 10-week training lasting 90 min/d of memory
      training. They benefited from an initial and a follow-up neuropsychological
      evaluation and resting-state electroencephalography (EEG). RESULTS: At follow-up,
      MST revealed an extensive significant training effect that changed the network
      with an increase of synchronization between parietotemporal and frontal areas;
      frontaltheta-parietalalpha2 causal strengthening as part of top-down inhibitory
      control; enhancement of sensorimotor connections in beta band; and a general
      increase of cortical-level integration. More precisely, MST induced gain as an
      increase of the global cost efficiency (GCE) of the whole cortical network and a
      neuropsychological performance improvement, which was correlated with it (r =
      0.32, P = .0001). The present study unfolded intervention changes based on EEG
      source activity via novel neuroinformatic tools for revealing intrinsic coupling
      modes in both amplitude-phase representations and in the mixed
      spectrospatiotemporal domain. DISCUSSION: Further work should identify whether
      the GCE enhancement of the functional cortical brain networks is a compensation
      mechanism to the brain network dysfunction or a more permanent neuroplasticity
      effect.

PMID- 29067312
TI  - A multicenter, randomized, placebo-controlled trial for cilostazol in patients
      with mild cognitive impairment: The COMCID study protocol.
AB  - INTRODUCTION: There are currently no effective treatments preventing conversion
      from mild cognitive impairment (MCI) to Alzheimer's disease. Cilostazol is a
      selective type-3 phosphodiesterase inhibitor that ameliorates accumulation of
      amyloid-beta and has prevented cognitive decline in rodent models. Furthermore,
      cilostazol is known to suppress platelet aggregation, protect vascular
      endothelia, dilate vessels, and increase cerebral blood flow. Beneficial effects
      have also been shown in observational cohort studies, demonstrating the need for
      a prospective clinical trial. METHODS: The Cilostazol for prevention of
      COnversion from MCI to Dementia (COMCID) study is a double-blind, randomized
      phase II study of patients with MCI. Participants will receive cilostazol or
      placebo for 96 weeks. The primary objective is to evaluate whether cilostazol
      slows down cognitive decline measured by the Mini-Mental State Examination.
      Secondary objectives are assessing time to conversion from MCI to dementia and
      assessing incremental changes in several psychological assessment scales.
      DISCUSSION: The COMCID trial will identify the therapeutic potential of
      cilostazol. This trial, which is based on a drug repositioning strategy, may aid
      the development of a neurovascular treatment for neurocognitive disorders.

PMID- 29067313
TI  - Measuring informed consent capacity in an Alzheimer's disease clinical trial.
AB  - INTRODUCTION: Accurately and efficiently determining a participant's capacity to
      consent to research is critically important to protect the rights of patients
      with Alzheimer's disease (AD). METHODS: Understanding of the informed consent
      document was assessed in 613 community-dwelling patients with mild-to-moderate AD
      enrolled in a randomized, placebo-controlled trial. Associations were examined
      between clinically determined capacity to consent and (1) patient demographics
      and clinical characteristics and (2) the Informed Consent Questionnaire (ICQ), an
      objective measurement of a participant's factual understanding and perceived
      understanding. RESULTS: A total of 453 (74%) participants were determined to have
      capacity to consent by clinical judgment. ICQ perceived understanding, race,
      measures of cognitive function, and caregiver time were all significantly
      associated with the determination of capacity in multivariate analyses.
      DISCUSSION: We found a significant association between capacity and disease
      severity level, caregiver time, race, and ICQ perceived understanding.

PMID- 29067314
TI  - SAR110894, a potent histamine H3-receptor antagonist, displays disease-modifying
      activity in a transgenic mouse model of tauopathy.
AB  - INTRODUCTION: Tau hyperphosphorylation and neurofibrillary tangles are
      histopathologic hallmarks of tauopathies. Histamine H3-receptor antagonists have
      been proposed to reduce tau hyperphosphorylation in preclinical models. METHODS:
      We evaluated the ability of SAR110894, a selective histamine H3-receptor
      antagonist, to inhibit tau pathology and prevent cognitive deficits in a tau
      transgenic mouse model (THY-Tau22). RESULTS: SAR110894 treatment for 6 months
      (but not 2 weeks) in THY-Tau22 mice decreased both tau hyperphosphorylation at
      pSer396-pSer404 (AD2 signal) in the hippocampus and the number of AT8
      (pSer199/202-Thr205) positive cells in the cortex and decreased the formation of
      neurofibrillary tangles in the cortex, hippocampus, and amygdala. Macrophage
      inflammatory protein 1-alpha messenger RNA expression was decreased in the
      hippocampus. SAR110894 also prevented episodic memory deficits, and this effect
      was still detected after treatment washout. DISCUSSION: Long-term SAR110894
      treatment could have potential disease modifying activity in neurodegenerative
      tauopathies.

PMID- 29067315
TI  - Tolerability of ORM-12741 and effects on episodic memory in patients with
      Alzheimer's disease.
AB  - INTRODUCTION: ORM-12741 is a novel selective antagonist of alpha-2C
      adrenoceptors. This trial evaluated the safety and efficacy of ORM-12741 in
      patients with Alzheimer's disease (AD). METHODS: A randomized, double-blind,
      placebo-controlled, exploratory phase 2a trial was conducted in 100 subjects with
      AD and neuropsychiatric symptoms. Participants were randomized to receive one of
      two flexible doses of ORM-12741 (30-60 mg or 100-200 mg) or placebo b.i.d. for 12
      weeks in addition to standard therapy with cholinesterase inhibitors. Efficacy
      was assessed primarily with the Cognitive Drug Research (CDR) computerized
      assessment system and secondarily with the Neuropsychiatric Inventory (NPI).
      RESULTS: A statistically significant treatment effect was seen in one of the four
      primary CDR system end points, Quality of Episodic Memory (P = .030; not adjusted
      for multiple comparisons), favoring ORM-12741 over placebo. NPI caregiver
      distress scores also favored ORM-12741 (P = .034). ORM-12741 was well tolerated.
      DISCUSSION: This is the first clinical trial providing evidence on an acceptable
      safety profile for ORM-12741 in patients with AD and neuropsychiatric symptoms.
      In addition, the trial provided hints of potential therapeutic benefit, primarily
      on episodic memory, in this patient population.

PMID- 29067316
TI  - Active Abeta immunotherapy CAD106 in Alzheimer's disease: A phase 2b study.
AB  - INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study
      assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant
      in patients with mild Alzheimer's disease. METHODS: One hundred twenty-one
      patients received up to seven intramuscular injections of CAD106 (150 MUg or 450
      MUg) or placebo +/- adjuvant over 60 weeks. An amyloid positron emission
      tomography (PET) substudy was also conducted. RESULTS: CAD106 induced strong
      serological responses (amyloid-beta [Abeta]-Immunoglobuline G[IgG]) in 55.1% (150
      MUg) and 81.1% (450 MUg) of patients (strong serological responders [SSRs]).
      Serious adverse events (SAEs) were reported in 24.5% (95% confidence interval
      [CI] 16.7-33.8) of the patients in the active treatment group and in 6.7% (95% CI
      0.2-31.9) in the placebo group. Three of the SAEs were classified as possibly
      related to study drug by the investigators. No evidence of central nervous system
      inflammation was found. Amyloid-related imaging abnormalities (ARIAs) occurred in
      six cases, all of them were strong serological responders. None of the ARIAs were
      symptomatic. Serum Abeta-IgG titer area under the curves correlated negatively
      with amyloid PET standardized uptake value ratio percentage change from baseline
      to week 78 within the CAD106-treated patients (r = -0.84, P = .0004). Decrease in
      cortical gray-matter volume from baseline to week 78 was larger in SSRs than in
      controls (P = .0077). DISCUSSION: Repeated CAD106 administration was generally
      well tolerated. CAD106 450 MUg with alum adjuvant demonstrated the best balance
      between antibody response and tolerability.

PMID- 29067317
TI  - Social interaction and cognitive decline: Results of a 7-year community
      intervention.
AB  - INTRODUCTION: There are few intervention studies that demonstrated linking social
      participation to lower risk of cognitive decline. We examined prospectively the
      protective effect of a community intervention program promoting social
      participation on the incidence of cognitive disability. METHODS: The baseline was
      established in a survey of community-dwelling older people aged 65 years old or
      more in July 2006 (2793 respondents, response rate 48.5%). The setting was
      Taketoyo town in Japan, where municipal authorities launched an intervention that
      was based on the establishment of community-based centers called "salons," where
      the town's senior residents could congregate and participate in social
      activities, ranging from arts and crafts, games, and interactive activities with
      preschool children. Three salons were established in May 2010, and a total of 10
      salons were in operation by 2013. We recorded the frequency of salon
      participation among survey respondents till 2013 and conducted two follow-up
      surveys (in 2010 and 2013) to collect information about health status and
      behaviors. The onset of cognitive disability was followed from May 2007 to
      January 2014. We used the marginal structural models to evaluate the effect of
      program. RESULTS: The range of prevalence of cognitive disability was from 0.2%
      to 2.5% during the observation period. The proportion of respondents who
      participates to salons increased over time to about 11.7%. The frequency of salon
      participation was protectively associated with cognitive decline, even after
      adjusting for time-dependent covariates and attrition (odds ratio = 0.73, 95%
      confidence interval: 0.54-0.99). DISCUSSION: Our study suggests that operating
      community salons that encourage social interactions, light physical activity, and
      cognitive activities among older participants may be effective for preventing
      cognitive decline. In future studies, we need to understand what sorts of
      activities (e.g., those involving light physical activity vs. purely intellectual
      activities) are most effective in maintaining cognitive function.

PMID- 29067318
TI  - Cyclic AC253, a novel amylin receptor antagonist, improves cognitive deficits in
      a mouse model of Alzheimer's disease.
AB  - INTRODUCTION: Amylin receptor serves as a portal for the expression of
      deleterious effects of amyloid beta-protein (Abeta), a key pathologic hallmark of
      Alzheimer's disease. Previously, we showed that AC253, an amylin receptor
      antagonist, is neuroprotective against Abeta toxicity in vitro and abrogates
      Abeta-induced impairment of hippocampal long-term potentiation. METHODS: Amyloid
      precursor protein-overexpressing TgCRND8 mice received intracerebroventricularly
      AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered
      intraperitoneally three times a week for 10 weeks in the same mouse model.
      Cognitive functions were monitored, and pathologic changes were quantified
      biochemically and immunohistochemically. RESULTS: AC253, when administered
      intracerebroventricularly, improves spatial memory and learning, increases
      synaptic integrity, reduces microglial activation without discernible adverse
      effects in TgCRND8 mice. cAC253 demonstrates superior brain permeability, better
      proteolytic stability, and enhanced binding affinity to brain amylin receptors
      after a single intraperitoneal injection. Furthermore, cAC253 administered
      intraperitoneally also demonstrates improvement in spatial memory in TgCRND8
      mice. DISCUSSION: Amylin receptor is a therapeutic target for Alzheimer's disease
      and represents a disease-modifying therapy for this condition.

PMID- 29067319
TI  - African Americans are less likely to enroll in preclinical Alzheimer's disease
      clinical trials.
AB  - INTRODUCTION: Alzheimer's disease (AD) incidence is disproportionately high in
      African Americans, yet, recruitment of this community to AD clinical trials is
      challenging. METHODS: We compared 47 African Americans and 78 whites in their
      willingness to enroll in a hypothetical preclinical AD trial and examined
      barriers and facilitators in their decision making. RESULTS: African American
      race (OR = 0.45; 95% CI, 0.22-0.93) and score on the research attitude
      questionnaire (OR = 1.12; 95% CI, 1.04-1.22) were independently associated with
      willingness to participate. African Americans rated study risks, the requirement
      of a study partner, study procedures, the ratio of drug to placebo, and study
      location as more important factors in the decision whether to enroll than did
      whites. DISCUSSION: These results suggest that researchers will encounter
      challenges in recruiting African Americans to preclinical AD trials. Future
      research will be necessary to understand the optimal means to improve recruitment
      of underrepresented populations.

PMID- 29067322
TI  - The prevalence and biomarkers' characteristic of rapidly progressive Alzheimer's
      disease from the Alzheimer's Disease Neuroimaging Initiative database.
AB  - INTRODUCTION: The prevalence and detailed biomarkers' characteristic of rapidly
      progressive Alzheimer's disease (rpAD) remain incompletely understood. METHODS: A
      total of 312 mild AD patients from the Alzheimer's Disease Neuroimaging
      Initiative database were chosen and dichotomized into rpAD and non-rpAD groups.
      We performed the prevalence and comprehensive biomarker evaluation. RESULTS: The
      prevalence of rpAD was 17.6% in mild AD. Compared with non-rpAD, there were no
      differences in APOE epsilon4/epsilon4, APOE epsilon3/epsilon4, and APOE
      epsilon2/epsilon4 genotype distribution, cerebrospinal fluid tau, phosphorylated
      tau (p-tau), amyloid-beta, hippocampus volume, and amyloid deposition in rpAD.
      Yet, a lower p-tau/tau ratio was observed in rpAD (P = .04). rpAD showed region
      specific hypometabolism ([18F]fluorodeoxyglucose-positron emission tomography
      [FDG-PET]) (P = .001). Receiver-operating characteristic analysis of FDG-PET
      demonstrated that left angular and left temporal cortices were the regions with
      higher area under the curve and predictive value for identifying clinical at-risk
      rpAD. DISCUSSION: We identified that rpAD commonly existed in mild AD. Cerebral
      hypometabolism could provide potential clinical differential value for rpAD in
      the short-term follow-up period.

PMID- 29067323
TI  - Intermittent hypoxic-hyperoxic training on cognitive performance in geriatric
      patients.
AB  - INTRODUCTION: Intermittent hypoxic-hyperoxic training (IHHT) may complement a
      multimodal training intervention (MTI) for improving cognitive function and
      exercise tolerance in geriatric patients. METHODS: Thirty-four patients (64-92
      years) participated in this randomized controlled trial. Before and after the 5-
      to 7-week intervention period (MTI + IHHT vs. MTI + ambient air), cognitive
      function was assessed by the Dementia-Detection Test (DemTect) and the Sunderland
      Clock-Drawing Test (CDT), and functional exercise capacity by the total distance
      of the 6-Minute Walk Test (6MWT). RESULTS: DemTect and CDT indicated
      significantly larger improvements after MTI + IHHT (+16.7% vs. -0.39%, P < .001)
      and (+10.7% vs. -8%, P = .031) which was also true for the 6MWT (+24.1% vs.
      +10.8%, P = .021). DISCUSSION: IHHT turned out to be easily applicable to and
      well tolerated by geriatric patients up to 92 years. IHHT contributed
      significantly to improvements in cognitive function and functional exercise
      capacity in geriatric patients performing MTI.

PMID- 29067320
TI  - Multiple comorbid neuropathologies in the setting of Alzheimer's disease
      neuropathology and implications for drug development.
AB  - Dementia is often characterized as being caused by one of several major diseases,
      such as Alzheimer's disease (AD), cerebrovascular disease, Lewy body disease, or
      a frontotemporal degeneration. Failure to acknowledge that more than one entity
      may be present precludes attempts to understand interactive relationships. The
      clinicopathological studies of dementia demonstrate that multiple pathologic
      processes often coexist. How overlapping pathologic findings affect the diagnosis
      and treatment of clinical AD and other dementia phenotypes was the topic taken up
      by the Alzheimer's Association's Research Roundtable in October 2014. This review
      will cover the neuropathologic basis of dementia, provide clinical perspectives
      on multiple pathologies, and discuss therapeutics and biomarkers targeting
      overlapping pathologies and how these issues impact clinical trials.High
      prevalence of multiple pathologic findings among individuals with clinical
      diagnosis of AD suggests that new treatment strategies may be needed to
      effectively treat AD and other dementing illnesses.

PMID- 29067321
TI  - Combination treatment with leptin and pioglitazone in a mouse model of
      Alzheimer's disease.
AB  - INTRODUCTION: Combination therapy approaches may be necessary to address the many
      facets of pathologic change in the brain in Alzheimer's disease (AD). The drugs
      leptin and pioglitazone have previously been shown individually to have
      neuroprotective and anti-inflammatory actions, respectively, in animal models.
      METHODS: We studied the impact of combined leptin and pioglitazone treatment in 6
      month-old APP/PS1 (APPswe/PSEN1dE9) transgenic AD mouse model. RESULTS: We report
      that an acute 2-week treatment with combined leptin and pioglitazone resulted in
      a reduction of spatial memory deficits (Y maze) and brain beta-amyloid levels
      (soluble beta-amyloid and amyloid plaque burden) relative to vehicle-treated
      animals. Combination treatment was also associated with amelioration in plaque
      associated neuritic pathology and synapse loss, and also a significantly reduced
      neocortical glial response. DISCUSSION: Combination therapy with leptin and
      pioglitazone ameliorates pathologic changes in APP/PS1 mice and may represent a
      potential treatment approach for AD.

PMID- 29067324
TI  - A composite measure of cognitive and functional progression in Alzheimer's
      disease: Design of the Capturing Changes in Cognition study.
AB  - INTRODUCTION: Cognitive testing in Alzheimer's disease (AD) is essential for
      establishing diagnosis, monitoring progression, and evaluating treatments.
      Assessments should ideally be brief, reliable, valid, and reflect clinically
      meaningful changes. There is a lack of instruments that meet all these criteria.
      In the Capturing Changes in Cognition (Catch-Cog) study, we seek to correct these
      deficiencies through the development and validation of a composite measure
      combining cognition and function: the cognitive-functional composite (CFC). We
      expect that the CFC is able to detect clinically relevant changes over time in
      early dementia stages of AD. METHODS/DESIGN: We will include patients (n = 350)
      with mild cognitive impairment or mild dementia due to AD from memory clinics in
      the Netherlands and the United Kingdom. We will include cognitively healthy
      volunteers (n = 30) as a control group. The CFC is based on the "cognitive
      composite" and the Amsterdam instrumental activities of daily living
      questionnaire. We will investigate test-retest reliability with baseline and 2-
      to 3-week follow-up assessments (n = 50 patients and n = 30 healthy controls). We
      will involve experts and participants to evaluate the initial feasibility and
      refine the CFC if needed. Subsequently, we will perform a longitudinal construct
      validation study in a prospective cohort (n = 300) with baseline, 3-, 6-, and 12
      month follow-up assessments. The main outcome is cognitive and functional
      progression measured by the CFC. Reference measures for progression include
      traditional cognitive and functional tests, disease burden measures, and brain
      imaging methods. Using linear mixed modeling, we will investigate longitudinal
      changes on the CFC and relate these to the reference measures. Using linear
      regression analyses, we will evaluate the influence of possible confounders such
      as age, gender, and education on the CFC. DISCUSSION: By performing an
      independent longitudinal construct validation, the Catch-Cog study of the novel
      CFC will contribute to the improvement of disease monitoring and treatment
      evaluation in early dementia stages of AD.

PMID- 29067325
TI  - Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral
      perfusion in patients with vascular cognitive impairment.
AB  - There is evidence for a beneficial effect of aerobic exercise on cognition, but
      underlying mechanisms are unclear. In this study, we test the hypothesis that
      aerobic exercise increases cerebral blood flow (CBF) in patients with vascular
      cognitive impairment (VCI). This study is a multicenter single-blind randomized
      controlled trial among 80 patients with VCI. Most important inclusion criteria
      are a diagnosis of VCI with Mini-Mental State Examination >=22 and Clinical
      Dementia Rating <=0.5. Participants are randomized into an aerobic exercise group
      or a control group. The aerobic exercise program aims to improve
      cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a
      week. Participants are provided with a bicycle ergometer at home. The control
      group receives two information meetings. Primary outcome measure is change in
      CBF. We expect this study to provide insight into the potential mechanism by
      which aerobic exercise improves hemodynamic status.

PMID- 29067326
TI  - Targeting butyrylcholinesterase for preclinical single photon emission computed
      tomography (SPECT) imaging of Alzheimer's disease.
AB  - INTRODUCTION: Diagnosis of Alzheimer's disease (AD) in vivo, by molecular imaging
      of amyloid or tau, is constrained because similar changes can be found in brains
      of cognitively normal individuals. Butyrylcholinesterase (BChE), which becomes
      associated with these structures in AD, could elevate the accuracy of AD
      diagnosis by focusing on BChE pathology in the cerebral cortex, a region of scant
      BChE activity in healthy brain. METHODS: N-methylpiperidin-4-yl 4
      [123I]iodobenzoate, a BChE radiotracer, was injected intravenously into B6SJL
      Tg(APPSwFlLon, PSEN1*M146 L*L286 V) 6799Vas/Mmjax (5XFAD) mice and their wild
      type (WT) counterparts for comparative single photon emission computed tomography
      (SPECT) studies. SPECT, computed tomography (CT), and magnetic resonance imaging
      (MRI) enabled comparison of whole brain and regional retention of the BChE
      radiotracer in both mouse strains. RESULTS: Retention of the BChE radiotracer was
      consistently higher in the 5XFAD mouse than in WT, and differences were
      particularly evident in the cerebral cortex. DISCUSSION: Cerebral cortical BChE
      imaging with SPECT can distinguish 5XFAD mouse model from the WT counterpart.

PMID- 29067328
TI  - Predicting mild cognitive impairment from spontaneous spoken utterances.
AB  - INTRODUCTION: Trials in Alzheimer's disease are increasingly focusing on
      prevention in asymptomatic individuals. We hypothesized that indicators of mild
      cognitive impairment (MCI) may be present in the content of spoken language in
      older adults and be useful in distinguishing those with MCI from those who are
      cognitively intact. To test this hypothesis, we performed linguistic analyses of
      spoken words in participants with MCI and those with intact cognition
      participating in a clinical trial. METHODS: Data came from a randomized
      controlled behavioral clinical trial to examine the effect of unstructured
      conversation on cognitive function among older adults with either normal
      cognition or MCI (ClinicalTrials.gov: NCT01571427). Unstructured conversations
      (but with standardized preselected topics across subjects) were recorded between
      interviewers and interviewees during the intervention sessions of the trial from
      14 MCI and 27 cognitively intact participants. From the transcription of
      interviewees recordings, we grouped spoken words using Linguistic Inquiry and
      Word Count (LIWC), a structured table of words, which categorizes 2500 words into
      68 different word subcategories such as positive and negative words, fillers, and
      physical states. The number of words in each LIWC word subcategory constructed a
      vector of 68 dimensions representing the linguistic features of each subject. We
      used support vector machine and random forest classifiers to distinguish MCI from
      cognitively intact participants. RESULTS: MCI participants were distinguished
      from those with intact cognition using linguistic features obtained by LIWC with
      84% classification accuracy which is well above chance 60%. DISCUSSION:
      Linguistic analyses of spoken language may be a powerful tool in distinguishing
      MCI subjects from those with intact cognition. Further studies to assess whether
      spoken language derived measures could detect changes in cognitive functions in
      clinical trials are warrented.

PMID- 29067327
TI  - Zfra restores memory deficits in Alzheimer's disease triple-transgenic mice by
      blocking aggregation of TRAPPC6ADelta, SH3GLB2, tau, and amyloid beta, and
      inflammatory NF-kappaB activation.
AB  - INTRODUCTION: Zinc finger-like protein that regulates apoptosis (Zfra) is a
      naturally occurring 31-amino-acid protein. Synthetic peptides Zfra1-31 and Zfra4
      10 are known to effectively block the growth of many types of cancer cells.
      METHODS: Ten-month-old triple-transgenic (3*Tg) mice for Alzheimer's disease (AD)
      received synthetic Zfra peptides via tail vein injections, followed by examining
      restoration of memory deficits. RESULTS: Zfra significantly downregulated
      TRAPPC6ADelta, SH3GLB2, tau, and amyloid beta (Alphabeta) aggregates in the
      brains of 3*Tg mice and effectively restored their memory capabilities. Zfra
      inhibited melanoma-induced neuronal death in the hippocampus and plaque formation
      in the cortex. Mechanistically, Zfra blocked the aggregation of amyloid beta 42
      and many serine-containing peptides in vitro, suppressed tumor necrosis factor
      mediated NF-kappaB activation, and bound cytosolic proteins for accelerating
      their degradation in ubiquitin/proteasome-independent manner. DISCUSSION: Zfra
      peptides exhibit a strong efficacy in blocking tau aggregation and amyloid
      Alphabeta formation and restore memory deficits in 3*Tg mice, suggesting its
      potential for treatment of AD.

PMID- 29067330
TI  - Differential medial temporal lobe morphometric predictors of item- and relational
      encoded memories in healthy individuals and in individuals with mild cognitive
      impairment and Alzheimer's disease.
AB  - INTRODUCTION: Episodic memory processes are supported by different subregions of
      the medial temporal lobe (MTL). In contrast to a unitary model of memory
      recognition supported solely by the hippocampus, a current model suggests that
      item encoding engages perirhinal cortex, whereas relational encoding engages
      parahippocampal cortex and the hippocampus. However, this model has not been
      examined in the context of aging, neurodegeneration, and MTL morphometrics.
      METHODS: Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects
      (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients)
      were assessed with the relational and item-specific encoding task (RISE) and
      underwent 3T magnetic resonance imaging. The RISE assessed the differential
      contribution of relational and item-specific memory. FreeSurfer was used to
      obtain measures of cortical thickness of MTL regions and hippocampus volume.
      RESULTS: Memory accuracies for both item and relational memory were significantly
      better in the HS group than in the MCI/AD group. In MCI/AD group, relational
      memory was disproportionately impaired. In HSs, hierarchical regressions
      demonstrated that memory was predicted by perirhinal thickness after item
      encoding, and by hippocampus volume after relational encoding (both at trend
      level) and significantly by parahippocampal thickness at associative recognition.
      The same brain morphometry profiles predicted memory accuracy in MCI/AD, although
      more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal
      volume and parahippocampal thickness for relational encoding (R2 = 0.31).
      DISCUSSION: Our results supported a model of episodic memory in which item
      specific encoding was associated with greater perirhinal cortical thickness,
      while relational encoding was associated with parahippocampal thickness and
      hippocampus volume. We identified these relationships not only in HSs but also in
      individuals with MCI and AD. In the subjects with cognitive impairment,
      reductions in hippocampal volume and impairments in relational memory were
      especially prominent.

PMID- 29067331
TI  - Inferior parietal transcranial direct current stimulation with training improves
      cognition in anomic Alzheimer's disease and frontotemporal dementia.
AB  - INTRODUCTION: We evaluated whether transcranial direct current stimulation (tDCS)
      can improve picture-naming abilities in subjects with anomic Alzheimer or
      frontotemporal dementias. METHODS: Using a double-blind crossover design, 10
      participants were trained on picture naming over a series of 10 sessions with
      either 30 minutes of anodal (2 mA) tDCS stimulation to the left inferior parieto
      temporal region (P3) or sham stimulation. We evaluated performance on a trained
      picture-naming list, an equivalent untrained list, and additional
      neuropsychological tasks. RESULTS: Participants improved significantly more
      receiving real stimulation rather than sham stimulation (40% vs. 19%, P < .01),
      lasting at least 2 weeks after stimulation. Furthermore, these participants
      showed a small increase for untrained picture-naming items and digit span when
      they received real stimulation but a decrease when sham stimulation was received.
      DISCUSSION: tDCS stimulation has promise as a treatment for anomia in demented
      individuals and the effect can generalize to unstudied items as well as other
      cognitive abilities.

PMID- 29067329
TI  - Associations between social relationship measures, serum brain-derived
      neurotrophic factor, and risk of stroke and dementia.
AB  - INTRODUCTION: Mechanisms underlying social determinants of stroke and dementia
      are unclear and brain-derived neurotrophic factor (BDNF) may contribute as a
      molecular link. METHODS: Using the Framingham Study, we examined social
      relationship measures as predictors of higher serum BDNF level and cumulative
      incidence of stroke and dementia. RESULTS: Among 3294 participants, controlling
      for age and sex, isolation trended with lower BDNF (odds ratio = 0.69 [0.47
      1.00]). Participants with more companionship had reduced risk for stroke (hazard
      ratio [HR] = 0.59 [0.41-0.83]) and dementia (HR = 0.67 [0.49-0.92]). Greater
      emotional support was associated with higher BDNF (odds ratio = 1.27 [1.04
      1.54]), reduced dementia risk (HR = 0.69 [0.51-0.94], and among smokers, reduced
      stroke risk (HR = 0.23 [0.10-0.57]). Associations persisted after additional
      adjustments. BDNF partly mediated the total effect between emotional support and
      dementia risk. CONCLUSIONS: Availability of social support appears to be
      associated with increased BDNF levels and, in certain subsets, reduce risk of
      subsequent dementia and stroke, thus warranting study of these pathways to
      understand their role in neuroprotection.

PMID- 29067332
TI  - UB-311, a novel UBITh(r) amyloid beta peptide vaccine for mild Alzheimer's
      disease.
AB  - INTRODUCTION: A novel amyloid beta (Abeta) synthetic peptide vaccine (UB-311) has
      been evaluated in a first-in-human trial with patients of mild-to-moderate
      Alzheimer's disease. We describe translational research covering vaccine design,
      preclinical characterization, and phase-I clinical trial with supportive outcome
      that advances UB-311 into an ongoing phase-II trial. METHODS: UB-311 is
      constructed with two synthetic Abeta1-14-targeting peptides (B-cell epitope),
      each linked to different helper T-cell peptide epitopes (UBITh(r)) and formulated
      in a Th2-biased delivery system. The hAPP751 transgenic mouse model was used to
      perform the proof-of-concept study. Baboons and macaques were used for
      preclinical safety, tolerability, and immunogenicity evaluation. Patients with
      mild-to-moderate Alzheimer's disease (AD) were immunized by intramuscular route
      with 3 doses of UB-311 at weeks 0, 4, and 12, and monitored until week 48. Safety
      and immunogenicity were assessed per protocol, and preliminary efficacy was
      analyzed by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog),
      Mini-Mental State Examination (MMSE), and Alzheimer's Disease Cooperative Study
      Clinician's Global Impression of Change (ADCS-CGIC). RESULTS: UB-311 covers a
      diverse genetic background and facilitates strong immune response with high
      responder rate. UB-311 reduced the levels of Abeta1-42 oligomers, protofibrils,
      and plaque load in hAPP751 transgenic mice. Safe and well-tolerated UB-311
      generated considerable site-specific (Abeta1-10) antibodies across all animal
      species examined. In AD patients, UB-311 induced a 100% responder rate; injection
      site swelling and agitation were the most common adverse events (4/19 each). A
      slower rate of increase in ADAS-Cog from baseline to week 48 was observed in the
      subgroup of mild AD patients (MMSE >= 20) compared with the moderate AD subgroup,
      suggesting that UB-311 may have a potential of cognition improvement in patients
      with early stage of Alzheimer's dementia. DISCUSSION: The UBITh(r) platform can
      generate a high-precision molecular vaccine with high responder rate, strong on
      target immunogenicity, and a potential of cognition improvement, which support UB
      311 for active immunotherapy in early-to-mild AD patients currently enrolled in a
      phase-II trial (NCT02551809).

PMID- 29067333
TI  - Accelerating drug development for Alzheimer's disease through the use of data
      standards.
AB  - INTRODUCTION: The exceedingly high rate of failed trials in Alzheimer's disease
      (AD) calls for immediate attention to improve efficiencies and learning from
      past, ongoing, and future trials. Accurate, highly rigorous standardized data are
      at the core of meaningful scientific research. Data standards allow for proper
      integration of clinical data sets and represent the essential foundation for
      regulatory endorsement of drug development tools. Such tools increase the
      potential for success and accuracy of trial results. METHODS: The development of
      the Clinical Data Interchange Standards Consortium (CDISC) AD therapeutic area
      data standard was a comprehensive collaborative effort by CDISC and Coalition
      Against Major Diseases, a consortium of the Critical Path Institute. Clinical
      concepts for AD and mild cognitive impairment were defined and a data standards
      user guide was created from various sources of input, including data dictionaries
      used in AD clinical trials and observational studies. RESULTS: A comprehensive
      collection of AD-specific clinical data standards consisting of clinical outcome
      measures, leading candidate genes, and cerebrospinal fluid and imaging biomarkers
      was developed. The AD version 2.0 (V2.0) Therapeutic Area User Guide was
      developed by diverse experts working with data scientists across multiple
      consortia through a comprehensive review and revision process. The AD CDISC
      standard is a publicly available resource to facilitate widespread use and
      implementation. DISCUSSION: The AD CDISC V2.0 data standard serves as a platform
      to catalyze reproducible research, data integration, and efficiencies in clinical
      trials. It allows for the mapping and integration of available data and provides
      a foundation for future studies, data sharing, and long-term registries in AD.
      The availability of consensus data standards for AD has the potential to
      facilitate clinical trial initiation and increase sharing and aggregation of data
      across observational studies and among clinical trials, thereby improving our
      understanding of disease progression and treatment.

PMID- 29067334
TI  - Effect of physical exercise on markers of neuronal dysfunction in cerebrospinal
      fluid in patients with Alzheimer's disease.
AB  - INTRODUCTION: Physical exercise has gained increasing focus as a potential mean
      to maintain cognitive function in patients with Alzheimer's disease (AD).
      Alongside the markers of specific AD pathology (amyloid beta and tau), other
      pathologies such as neuronal damage and synaptic loss have been proposed as
      markers of the disease. Here, we study the effect of physical exercise on
      biomarkers of neuronal and synaptic integrity. METHODS: Cerebrospinal fluid (CSF)
      from 51 AD subjects who participated in the randomized controlled trial
      Preserving Cognition, Quality of Life, Physical Health and Functional Ability in
      Alzheimer's Disease: The Effect of Physical Exercise (ADEX) was analyzed for the
      concentration of neurofilament light (NFL), neurogranin (Ng), visinin-like
      protein-1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Participants were
      subjected to either 16 weeks of moderate- to high-intensity exercise (n = 25) or
      treatment as usual (control group, n = 26), and CSF was collected before and
      after intervention. RESULTS: No significant differences in CSF concentrations of
      VILIP-1, YKL-40, NFL, and Ng were observed when comparing mean change from
      baseline between the exercise and control groups. Similarly, when classifying
      subjects based on their exercise levels, no significant changes were observed for
      the biomarkers in the control group compared with the high-exercise group
      (attending 80% of the exercise sessions with an intensity of 70% of maximum heart
      rate or above). DISCUSSION: These results are not supportive of a modulatory
      effect of physical exercise on the selected biomarkers of neuronal and synaptic
      integrity in patients with AD.

PMID- 29067336
TI  - Diagnostic dilemmas in Alzheimer's disease: Room for shared decision making.
AB  - The launch of the NIA-AA research criteria for Alzheimer's disease (AD) diagnosis
      illustrates the large advances that have been made in the field of AD diagnosis.
      These new possibilities however also introduce new dilemmas into the consulting
      room, and this provides room for shared decision making (SDM). SDM refers to
      clinicians and patients (and/or their caregivers) working together to decide
      which care plan best fits individual patients and their lives, when there is more
      than one reasonable option. Here, we describe how SDM in the diagnosis of AD
      promotes patient-centered care, as it helps to adapt the diagnostic process to
      the patients' values and preferences. We provide an outline for a research
      agenda, as SDM in the diagnosis of dementia should be studied intensively
      incorporating the views of both patients and caregivers.

PMID- 29067335
TI  - Sedentary behavior as a risk factor for cognitive decline? A focus on the
      influence of glycemic control in brain health.
AB  - Cognitive decline leading to dementia represents a global health burden. In the
      absence of targeted pharmacotherapy, lifestyle approaches remain the best option
      for slowing the onset of dementia. However, older adults spend very little time
      doing moderate to vigorous exercise and spend a majority of time in sedentary
      behavior. Sedentary behavior has been linked to poor glycemic control and
      increased risk of all-cause mortality. Here, we explore a potential link between
      sedentary behavior and brain health. We highlight the role of glycemic control in
      maintaining brain function and suggest that reducing and replacing sedentary
      behavior with intermittent light-intensity physical activity may protect against
      cognitive decline by reducing glycemic variability. Given that older adults find
      it difficult to achieve current exercise recommendations, this may be an
      additional practical strategy. However, more research is needed to understand the
      impact of poor glycemic control on brain function and whether practical
      interventions aimed at reducing and replacing sedentary behavior with
      intermittent light intensity physical activity can help slow cognitive decline.

PMID- 29067337
TI  - Clinicians' views on conversations and shared decision making in diagnostic
      testing for Alzheimer's disease: The ABIDE project.
AB  - INTRODUCTION: This study explores clinicians' views on and experiences with when,
      how, and by whom decisions about diagnostic testing for Alzheimer's disease are
      made and how test results are discussed with patients. METHODS: Following a
      preparatory focus group with 13 neurologists and geriatricians, we disseminated
      an online questionnaire among 200 memory clinic clinicians. RESULTS: Respondents
      were 95 neurologists and geriatricians (response rate 47.5%). Clinicians (74%)
      indicated that decisions about testing are made before the first encounter, yet
      they favored a shared decision-making approach. Patient involvement seems limited
      to receiving information. Clinicians with less tolerance for uncertainty
      preferred a bigger say in decisions (P < .05). Clinicians indicated to always
      communicate the diagnosis (94%), results of different tests (88%-96%), and risk
      of developing dementia (66%). DISCUSSION: Clinicians favor patient involvement in
      deciding about diagnostic testing, but conversations about decisions and test
      results can be improved and supported.

PMID- 29067338
TI  - Patients' and caregivers' views on conversations and shared decision making in
      diagnostic testing for Alzheimer's disease: The ABIDE project.
AB  - INTRODUCTION: This study aims to assess patients' and caregivers' views on and
      experiences with (1) decisions about diagnostic testing for Alzheimer's disease
      (AD) and (2) receiving test results. METHODS: We conducted separate focus groups
      with patients from three hospitals who underwent diagnostic testing for AD (N =
      11) and their caregivers (N = 11). Audio recordings were transcribed verbatim and
      analyzed using MaxQDA. RESULTS: Patients and caregivers preferred and perceived
      active involvement in decision making, but the decision to initiate diagnostic
      testing seems to be made before the clinician-patient encounter. Patients and
      caregivers indicate that decisions are driven by a strong need to explain the
      patient's symptoms. They missed information on why different diagnostic tests
      were used, what the results of these tests were, and to what extent these results
      were (ab)normal. DISCUSSION: The decision-making process around diagnostic
      testing for AD and the information provision before and after diagnostic testing
      could be improved.

PMID- 29067340
TI  - Technology for home dementia care: A prototype locating system put to the test.
AB  - INTRODUCTION: The user experience of persons with dementia and their primary
      caregivers with locating systems is not firmly established. METHODS: Eighteen
      dyads used a prototype locating system during 4 weeks. Primary outcome measures
      were ratings of usability, and product functions and features. Secondary outcome
      measures were caregiver burden, perceived self-efficacy, frequency of use, and
      willingness to purchase the prototype. Changes in scores between baseline (T1)
      and end of testing period (T2) were compared by performing independent and
      dependent samples correlations and descriptive statistics. RESULTS: Seventeen
      dyads made up the final sample. Ratings of usability and product functions and
      features were fair, but usability ratings were significantly reduced after 4
      weeks. Although the prototype was used infrequently by majority of the
      participants, most caregivers would be willing to purchase the prototype, with
      men more willing than women. No significant change in technological willingness,
      caregiver burden, or perceived self-efficacy was found between T1 and T2.
      Perceived self-efficacy significantly negatively correlated with willingness to
      purchase the prototype after 4 weeks. DISCUSSION: Results highlight the
      importance of including end users in the research and development phase of
      locating systems to improve the user experience in home dementia care. Necessary
      indications for further research are carrying out randomized controlled trials
      with larger, more representative samples and developing innovative software and
      hardware solutions.

PMID- 29067339
TI  - The BDNF Val66Met polymorphism moderates the effect of cognitive reserve on 36
      month cognitive change in healthy older adults.
AB  - INTRODUCTION: Cognitive reserve (CR) and BDNF Val66Met are independently
      associated with the rate of cognitive decline in preclinical Alzheimer's disease.
      This study was designed to investigate the interactive effects of these variables
      on 36-month cognitive change in cognitively intact older adults. METHODS: Data
      for this investigation were obtained from 445 community-residing participants of
      the Tasmanian Healthy Brain Project, who underwent genetic screening and annual
      assessment of neuropsychological, health, and psychosocial function. RESULTS: Our
      main result was that BDNF Val66Met moderated the relationship between baseline CR
      and change in executive function performance, in that CR-related differences in
      function decreased across the follow-up period in BDNF Val homozygotes, but
      became more pronounced in BDNF Met carriers. Similar effects were not observed
      within the other memory- and language-related cognitive domains. DISCUSSION:
      Inheritance of BDNF Met may be associated with a detrimental influence on the
      relationship between CR and cognitive change in cognitively intact older adults,
      but this effect may be restricted to the executive function domain.

PMID- 29067341
TI  - Multiple-dose ponezumab for mild-to-moderate Alzheimer's disease: Safety and
      efficacy.
AB  - INTRODUCTION: Multiple intravenous doses of ponezumab, an anti-amyloid antibody,
      were evaluated in subjects with mild-to-moderate Alzheimer's disease (AD).
      METHODS: In part A, 77 subjects were randomized to ponezumab 0.1, 0.5, or 1 mg/kg
      (75 treated) and 26 to placebo (24 treated). In part B, 63 subjects were
      randomized and treated with ponezumab 3 or 8.5 mg/kg and 32 with placebo.
      Subjects received 10 infusions over 18 months and were followed for 6 months
      thereafter. RESULTS: Ponezumab was generally safe and well tolerated. Most common
      adverse events were fall (16.7% ponezumab, 21.4% placebo), headache (13.8%,
      21.4%), and cerebral microhemorrhage (13.8%, 19.6%). Plasma ponezumab increased
      dose-dependently with limited accumulation. Cerebrospinal fluid penetration was
      low. Plasma Abeta1-x and Abeta1-40 showed robust increases, but cerebrospinal
      fluid biomarkers showed no dose response. Ponezumab had no effects on
      cognitive/functional outcomes or brain volume. CONCLUSIONS: Multiple-dose
      ponezumab was generally safe, but not efficacious, in mild-to-moderate AD.

PMID- 29067342
TI  - The effects of noncoding aquaporin-4 single-nucleotide polymorphisms on cognition
      and functional progression of Alzheimer's disease.
AB  - INTRODUCTION: The glymphatic system is a brain-wide perivascular network that
      facilitates clearance of proteins, including amyloid beta, from the brain
      interstitium through the perivascular exchange of cerebrospinal fluid and
      interstitial fluid. The astrocytic water channel aquaporin-4 (AQP4) is required
      for glymphatic system function, and impairment of glymphatic function in the
      aging brain is associated with altered AQP4 expression and localization. In human
      cortical tissue, alterations in AQP4 expression and localization are associated
      with Alzheimer's disease (AD) status and pathology. Although this suggests a
      potential role for AQP4 in the development or progression of AD, the relationship
      between of naturally occurring variants in the human AQP4 gene and cognitive
      function has not yet been evaluated. METHODS: Using data from several
      longitudinal aging cohorts, we investigated the association between five AQP4
      single-nucleotide polymorphisms (SNPs) and the rate of cognitive decline in
      participants with a diagnosis of AD. RESULTS: None of the five SNPs were
      associated with different rates of AD diagnosis, age of dementia onset in trial
      subjects. No association between AQP4 SNPs with histological measures of AD
      pathology, including Braak stage or neuritic plaque density was observed.
      However, AQP4 SNPs were associated with altered rates of cognitive decline after
      AD diagnosis, with two SNPS (rs9951307 and rs3875089) associated with slower
      cognitive decline and two (rs3763040 and rs3763043) associated with more rapid
      cognitive decline after AD diagnosis. DISCUSSION: These results provide the first
      evidence that variations in the AQP4 gene, whose gene product AQP4 is vital for
      glymphatic pathway function, may modulate the progression of cognitive decline in
      AD.

PMID- 29067343
TI  - Alzheimer's disease drug development pipeline: 2017.
AB  - INTRODUCTION: There is an urgent need to develop new treatments for Alzheimer's
      disease (AD) and to understand the drug development process for new AD therapies.
      METHODS: We assessed the agents in the AD pipeline as documented in
      clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017.
      RESULTS: There are 105 agents in the AD treatment development pipeline, of which
      25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II,
      and 28 agents are in 42 trials in phase III. Seventy percent of drugs in the AD
      pipeline are disease-modifying therapies (DMTs). Fourteen percent are symptomatic
      cognitive enhancers, and 13% are symptomatic agents addressing neuropsychiatric
      and behavioral changes (2% have undisclosed mechanisms). Most trials are
      sponsored by the biopharmaceutical industry. Trials include patients with
      preclinical AD (cognitively normal with biomarker evidence of AD), prodromal AD
      (mild cognitive symptoms and biomarker evidence of AD), and AD dementia.
      Biomarkers are included in many drug development programs particularly those for
      DMTs. Thirteen of 46 phase II DMT trials have amyloid imaging as an entry
      criterion, and 10 of 28 phase III trials incorporate amyloid imaging for
      diagnosis and entry. A large number of participants are needed for AD clinical
      trials; in total, 54,073 participants are required for trials spanning
      preclinical AD to AD dementia. When compared with the 2016 pipeline, there are
      eight new agents in phase I, 16 in phase II, and five in phase III. DISCUSSION:
      The AD drug development pipeline has 105 agents divided among phase I, phase II,
      and phase III. The trials include a wide range of clinical trial populations,
      many mechanisms of action, and require a substantial number of clinical trial
      participants. Biomarkers are increasingly used in patient identification and as
      outcome measures, particularly in trials of DMTs.

PMID- 29067344
TI  - Determining the impact of psychosis on rates of false-positive and false-negative
      diagnosis in Alzheimer's disease.
AB  - INTRODUCTION: The rate of clinical misdiagnosis of Alzheimer's disease (AD) and
      how psychosis impacts that clinical judgment is unclear. METHODS: Using data from
      National Alzheimer's Coordinating Center, we compared the clinical and
      neuropathologic diagnosis in patients with a diagnosis of AD with autopsy and in
      neuropathology-confirmed AD cases (n = 961). We determined the rate of true
      positives, false positives, and false negatives in patients with and without
      psychosis. RESULTS: A total of 76% received a correct AD diagnosis, 11.9% had a
      false-negative diagnosis, and 12.1% had a false-positive diagnosis of AD.
      Psychotic patients had a higher rate of false-negative diagnosis and a lower rate
      of false-positive diagnosis of AD compared with nonpsychotic patients.
      DISCUSSION: Patients with psychosis were five times more likely to be
      misdiagnosed as dementia with Lewy bodies, whereas patients without psychosis
      were more likely to be falsely diagnosed with AD when vascular pathology is the
      underlying neuropathologic cause of dementia.

PMID- 29067345
TI  - Ponezumab in mild-to-moderate Alzheimer's disease: Randomized phase II PET-PIB
      study.
AB  - INTRODUCTION: The safety, pharmacokinetics, and effect on peripheral and central
      amyloid beta (Abeta) of multiple doses of ponezumab, an anti-Abeta monoclonal
      antibody, were characterized in subjects with mild-to-moderate Alzheimer's
      disease treated for 1 year. METHODS: Subjects were aged >=50 years with Mini
      Mental State Examination scores 16 to 26. Cohort Q was randomized to ponezumab 10
      mg/kg (n = 12) or placebo (n = 6) quarterly. Cohort M was randomized to a loading
      dose of ponezumab 10 mg/kg or placebo, followed by monthly ponezumab 7.5 mg/kg (n
      = 12) or placebo (n = 6), respectively. RESULTS: Ponezumab was generally well
      tolerated. Plasma concentrations increased dose dependently, but cerebrospinal
      fluid (CSF) penetration was low. Plasma Abeta increased dose dependently with
      ponezumab, but CSF biomarkers, brain amyloid burden, cognition, and function were
      not affected. CONCLUSIONS: Both ponezumab dosing schedules were generally safe
      and well tolerated but did not alter CSF biomarkers, brain amyloid burden, or
      clinical outcomes.

PMID- 29067346
TI  - Phase II clinical trials of anti-amyloid beta antibodies: When is enough, enough?
AB  - Efforts to develop new therapies to combat Alzheimer's disease suffer from
      extraordinarily high failure rates that make it difficult to justify continued
      investment in the field. Although there are a number of plausible explanations
      for this extremely high attrition rate, one of the explanations that has received
      little attention is the lack of compelling data from Phase II studies for
      compounds that have been pushed into Phase III trials and then have failed. An
      analysis of publicly available data from the Phase II studies for bapineuzumab
      and solanezumab indicates that neither compound produced compelling evidence of
      drug-like behavior that would justify their progression into pivotal trials. The
      published data suggest that sponsors took decisions to move these compounds into
      Phase III on the basis of vastly limited data that were rife with type I error
      and probably driven by commercial concerns. The continued push to move compounds
      that are not likely to succeed in later stage clinical trials threatens to erode
      trust in the clinical research enterprise making it much harder to properly test
      truly promising compounds.

PMID- 29067347
TI  - A randomized feasibility pilot trial of hearing treatment for reducing cognitive
      decline: Results from the Aging and Cognitive Health Evaluation in Elders Pilot
      Study.
AB  - INTRODUCTION: Hearing loss (HL) is prevalent and independently related to
      cognitive decline and dementia. There has never been a randomized trial to test
      if HL treatment could reduce cognitive decline in older adults. METHODS: A 40
      person (aged 70-84 years) pilot study in Washington County, MD, was conducted.
      Participants were randomized 1:1 to a best practices hearing or successful aging
      intervention and followed for 6 months. clinicaltrials.gov Identifier:
      NCT02412254. RESULTS: The Aging and Cognitive Health Evaluation in Elders Pilot
      (ACHIEVE-P) Study demonstrated feasibility in recruitment, retention, and
      implementation of interventions with no treatment-related adverse events. A clear
      efficacy signal of the hearing intervention was observed in perceived hearing
      handicap (mean of 0.11 to -1.29 standard deviation [SD] units; lower scores
      better) and memory (mean of -0.10 SD to 0.38 SD). DISCUSSION: ACHIEVE-P sets the
      stage for the full-scale ACHIEVE trial (N = 850, recruitment beginning November
      2017), the first randomized trial to determine efficacy of a best practices
      hearing (vs. successful aging) intervention on reducing cognitive decline in
      older adults with HL.

PMID- 29067349
TI  - Serum concentrations of vitamin E and carotenoids are altered in Alzheimer's
      disease: A case-control study.
AB  - INTRODUCTION: Oxidative stress has been implicated in the pathogenesis of
      Alzheimer's disease (AD). We investigated associations between serum levels of
      lipophilic antioxidants and AD. METHODS: Serum concentrations of retinol, two
      forms of vitamin E (alpha- and gamma-tocopherol) and six carotenoids were
      quantified by high-performance liquid chromatography from patients with AD (n =
      251) and cognitively intact controls (n = 308) and assessed by regression
      analyses. RESULTS: Serum levels of alpha-tocopherol and all six carotenoids were
      significantly lower in patients with AD compared with cognitively intact controls
      (P < .001). In contrast, gamma-tocopherol was significantly higher in the serum
      of patients with AD (odds ratio = 1.17 [confidence intervals: 1.05-1.31]).
      DISCUSSION: Our findings implicate compromised serum antioxidant defenses in AD
      pathogenesis and differing biological roles for vitamin E isoforms. This
      highlights the need for improved understanding in the balanced upregulation of
      exogenous antioxidants related to dietary intake or supplement use in future
      nutritional intervention studies.

PMID- 29067348
TI  - Lower brain and blood nutrient status in Alzheimer's disease: Results from meta
      analyses.
AB  - INTRODUCTION: Alzheimer's disease (AD) patients are at risk of nutritional
      insufficiencies because of physiological and psychological factors. Recently, we
      showed the results of the meta-analyses indicating lower plasma levels of
      vitamins A, B12, C, E, and folate in AD patients compared with cognitively intact
      elderly controls (controls). Now, additional and more extensive literature
      searches were performed selecting studies which compare blood and
      brain/cerebrospinal fluid (CSF) levels of vitamins, minerals, trace elements,
      micronutrients, and fatty acids in AD patients versus controls. METHODS: The
      literature published after 1980 in Cochrane Central Register of Controlled
      Trials, Medline, and Embase electronic databases was systematically analyzed
      using Preferred Reporting Items for Systematic reviews and Meta-Analyses
      guidelines to detect studies meeting the selection criteria. Search terms used
      are as follows: AD patients, Controls, vitamins, minerals, trace elements,
      micronutrients, and fatty acids. Random-effects meta-analyses using a linear
      mixed model with correction for age differences between AD patients and controls
      were performed when four or more publications were retrieved for a specific
      nutrient. RESULTS: Random-effects meta-analyses of 116 selected publications
      showed significant lower CSF/brain levels of docosahexaenoic acid (DHA), choline
      containing lipids, folate, vitamin B12, vitamin C, and vitamin E. In addition, AD
      patients showed lower circulatory levels of DHA, eicosapentaenoic acid, choline
      as phosphatidylcholine, and selenium. CONCLUSION: The current data show that
      patients with AD have lower CSF/brain availability of DHA, choline, vitamin B12,
      folate, vitamin C, and vitamin E. Directionally, brain nutrient status appears to
      parallel the lower circulatory nutrient status; however, more studies are
      required measuring simultaneously circulatory and central nutrient status to
      obtain better insight in this observation. The brain is dependent on nutrient
      supply from the circulation, which in combination with nutrient involvement in AD
      pathophysiological mechanisms suggests that patients with AD may have specific
      nutritional requirements. This hypothesis could be tested using a multicomponent
      nutritional intervention.

PMID- 29067351
TI  - A comprehensive approach to reablement in dementia.
AB  - As society grapples with an aging population and increasing prevalence of
      disability, "reablement" as a means of maximizing functional ability in older
      people is emerging as a potential strategy to help promote independence.
      Reablement offers an approach to mitigate the impact of dementia on function and
      independence. This article presents a comprehensive reablement approach across
      seven domains for the person living with mild-to-moderate dementia. Domains
      include assessment and medical management, cognitive disability, physical
      function, acute injury or illness, assistive technology, supportive care, and
      caregiver support. In the absence of a cure or ability to significantly modify
      the course of the disease, the message for policy makers, practitioners,
      families, and persons with dementia needs to be "living well with dementia", with
      a focus on maintaining function for as long as possible, regaining lost function
      when there is the potential to do so, and adapting to lost function that cannot
      be regained. Service delivery and care of persons with dementia must be
      reoriented such that evidence-based reablement approaches are integrated into
      routine care across all sectors.

PMID- 29067352
TI  - Combined mnemonic strategy training and high-definition transcranial direct
      current stimulation for memory deficits in mild cognitive impairment.
AB  - INTRODUCTION: Memory deficits characterize Alzheimer's dementia and the clinical
      precursor stage known as mild cognitive impairment. Nonpharmacologic
      interventions hold promise for enhancing functioning in these patients,
      potentially delaying functional impairment that denotes transition to dementia.
      Previous findings revealed that mnemonic strategy training (MST) enhances long
      term retention of trained stimuli and is accompanied by increased blood oxygen
      level-dependent signal in the lateral frontal and parietal cortices as well as in
      the hippocampus. The present study was designed to enhance MST generalization,
      and the range of patients who benefit, via concurrent delivery of transcranial
      direct current stimulation (tDCS). METHODS: This protocol describes a
      prospective, randomized controlled, four-arm, double-blind study targeting memory
      deficits in those with mild cognitive impairment. Once randomized, participants
      complete five consecutive daily sessions in which they receive either active or
      sham high definition tDCS over the left lateral prefrontal cortex, a region known
      to be important for successful memory encoding and that has been engaged by MST.
      High definition tDCS (active or sham) will be combined with either MST or
      autobiographical memory recall (comparable to reminiscence therapy). Participants
      undergo memory testing using ecologically relevant measures and functional
      magnetic resonance imaging before and after these treatment sessions as well as
      at a 3-month follow-up. Primary outcome measures include face-name and object
      location association tasks. Secondary outcome measures include self-report of
      memory abilities as well as a spatial navigation task (near transfer) and prose
      memory (medication instructions; far transfer). Changes in functional magnetic
      resonance imaging will be evaluated during both task performance and the resting
      state using activation and connectivity analyses. DISCUSSION: The results will
      provide important information about the efficacy of cognitive and neuromodulatory
      techniques as well as the synergistic interaction between these promising
      approaches. Exploratory results will examine patient characteristics that affect
      treatment efficacy, thereby identifying those most appropriate for intervention.

PMID- 29067350
TI  - Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment
      paradigms.
AB  - Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimer's disease (AD),
      causing substantial distress for both people with dementia and their caregivers,
      and contributing to early institutionalization. They are among the earliest signs
      and symptoms of neurocognitive disorders and incipient cognitive decline, yet are
      under-recognized and often challenging to treat. With this in mind, the
      Alzheimer's Association convened a Research Roundtable in May 2016, bringing
      together experts from academia, industry, and regulatory agencies to discuss the
      latest understanding of NPSs and review the development of therapeutics and
      biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD
      and specific symptoms common in AD such as psychosis, agitation, apathy,
      depression, and sleep disturbances. In addition, clinical trial designs for NPSs
      in AD and regulatory considerations will be discussed.

PMID- 29067353
TI  - Midlife anticholinergic drug use, risk of Alzheimer's disease, and brain atrophy
      in community-dwelling older adults.
AB  - INTRODUCTION: We examined how long-term anticholinergic (AC) drug use beginning
      at midlife affects risk of Alzheimer's disease (AD) and rates of brain atrophy in
      cognitively normal older adults. METHODS: We followed 723 individuals (mean
      baseline age 52.3 years; mean follow-up interval 20.1 years) in the Baltimore
      Longitudinal Study of Aging. The AC drug exposure was defined using the
      Anticholinergic Cognitive Burden Scale: Nonusers (n = 404), as well as
      participants exposed to medications with AC activity but without known clinically
      relevant negative cognitive effects (i.e., "possible AC users"; n = 185) and
      those exposed to AC drugs with established and clinically relevant negative
      cognitive effects (i.e., "definite AC users"; n = 134). The neuroimaging sample
      included 93 participants who remained cognitively normal through follow-up and
      underwent serial magnetic resonance imaging (n = 93, 724 brain scans, mean follow
      up interval 8.2 years, and baseline age 68.6 years). RESULTS: Possible AC users,
      but not definite AC users, showed increased risk of incident AD compared with
      nonusers (hazard ratio, 1.63; 95% confidence interval, 1.02-2.61; P = .04) and
      greater rates of atrophy in total cortical gray matter volume compared with
      nonusers (beta = -0.74, P = .018). Faster rates of brain atrophy were also
      observed among possible AC users in the right posterior cingulate, as well as
      right middle frontal and left superior temporal gyri. Data on frequency and
      duration of medication use were available in only approximately half of the
      sample. Among these participants, definite AC users had both shorter duration and
      lower frequency of medication use relative to possible AC users. DISCUSSION: Long
      term exposure to medications with mild AC activity during midlife is associated
      with increased risk of AD and accelerated brain atrophy.

PMID- 29067355
TI  - Optimum duration of dual antiplatelet treatment could be decided using 64-MDCT: A
      new hint to treating patients with stents.

PMID- 29067354
TI  - Associations of increased arterial stiffness with left ventricular ejection
      performance and right ventricular systolic pressure in mitral regurgitation
      before and after surgery: Wave intensity analysis.
AB  - BACKGROUND: The effect of increased arterial stiffness on mitral regurgitation
      (MR) is not clear. Using wave intensity (WI) analysis, which is useful for
      analyzing ventriculo-arterial interaction, we aimed to elucidate associations of
      increased arterial stiffness with left ventricular (LV) ejection performance and
      right ventricular systolic pressure (RVSP) in MR. METHODS AND RESULTS: We
      noninvasively measured carotid arterial WI and stiffness parameter (beta) in 98
      patients with non-ischemic chronic MR before and after surgery, and 98 age-and
      gender matched healthy subjects by ultrasonography. WI is defined as WI =
      (dP/dt)(dU/dt) [P: blood pressure, U: velocity, t: time]. The peak value of WI
      (W1) increases with LV peak dP/dt. The temporal WI index (Q-W1)st, which is the
      standardized interval between the Q wave of the ECG and W1, is a surrogate for
      preejection period. Ejection fraction (EF), left atrial volume index (LAVI),
      effective regurgitant orifice area (ERO), RVSP, and other echocardiographic data
      were also obtained. W1 was enhanced in the MR group before surgery compared with
      the normal group (10.7 +/- 5.7 vs 8.5 +/- 3.6 * 103 mmHg m/s3, p < 0.05).
      However, the results of two-way ANOVA showed this enhancement of W1 was observed
      only in the subgroup of MR before surgery with lower arterial stiffness (beta <
      13, p< 0.0001). ERO, beta and LAVI were predictor variables before surgery to
      determine RVSP. EF and (Q-W1)st before surgery were predictor variables for EF
      after surgery. CONCLUSIONS: In the MR group before surgery, increased arterial
      stiffness suppresses compensatory enhancement of W1, and increases RVSP.
      Prolonged (Q-W1)st has the potential for predicting low EF after surgery.

PMID- 29067358
TI  - Asymmetric vanadium flow batteries: long lifespan via an anolyte overhang
      strategy.
AB  - Fast capacity decay is a serious problem in vanadium flow batteries (VFBs). How
      to eliminate or slow down capacity fading has become a critical issue for the
      practical application of VFBs. Herein, the concept of an asymmetric vanadium flow
      battery (aVFB) is introduced, in which the asymmetric design of a catholyte and
      an anolyte is used to suppress the capacity decay of the VFB. Based on the
      comprehensive analysis of the capacity decay and electrolyte imbalance process of
      the traditional symmetric VFB, it was found that the capacity fading is mainly
      owing to the loss of the anolyte in the long-term cycling test. Therefore, this
      work attempts to use excess anolyte (i.e. 10%, 20% and 30%) to mitigate the
      capacity decay during the long-term operation of the VFB. To gain deeper insights
      into the capacity retention mechanism of these novel anolyte overhang aVFBs, long
      term cycle performance of the corresponding symmetric overhang VFBs and catholyte
      overhang aVFBs is investigated for comparison. The optimal excess ratio of
      anolyte and how to add the excess anolyte are also suggested for future study.

PMID- 29067357
TI  - Use of 21-gene recurrence score assay to individualize adjuvant chemotherapy
      recommendations in ER+/HER2- node positive breast cancer-A National Cancer
      Database study.
AB  - The 21-gene Recurrence Score (RS) assay is prognostic and predictive of adjuvant
      chemotherapy benefit in node positive (N+) breast cancer (BC). We sought to
      evaluate use patterns of RS assay in N+, ER+/HER2- BC and the impact of RS on
      recommendations for adjuvant chemotherapy. Patients with T1-T4c,N1mi-N3, ER+/HER2
      BC diagnosed 2010-2013 in the National Cancer Database were analyzed.
      Multivariable logistic regression assessed factors influencing RS testing and
      chemotherapy recommendations based on RS. Among 72,897 patients, RS was obtained
      in 20.6%, increasing from 15.0% in 2010 to 24.5% in 2013 (p < 0.001). RS testing
      was most common in N1mi (43.7%) followed by N1 (22.1%) and rare in N2/N3 (3.3%).
      Of the 12,536 with quantitative RS results, 61.1% were low RS, 32.3% intermediate
      RS and 6.6% high RS. Chemotherapy was recommended less frequently in patients
      with RS testing (50.4%) vs. those not tested (81.0%, p < 0.001). In N1mi/N1
      patients, chemotherapy recommendation varied by RS; however, in N2/N3 patients,
      chemotherapy was recommended in the majority (70.9-87.5%) regardless of RS. Most
      patients (>85%) with RS >= 26 were recommended chemotherapy regardless of nodal
      stage. For patients with RS < 26, chemotherapy recommendations increased with
      higher N and T stage, grade, and younger age (p < 0.001). Histology was not
      associated with chemotherapy recommendation in any RS subset. The RS assay is
      frequently and increasingly being used for decision making in node positive
      ER+/HER2- breast cancer patients and its use is associated with lower rates of
      adjuvant chemotherapy.

PMID- 29067359
TI  - The reductive phase of Rhodobacter sphaeroides cytochrome c oxidase disentangled
      by CO ligation.
AB  - Cytochrome c oxidase (CcO) is a membrane protein of the respiratory chain that
      catalytically reduces molecular oxygen (O2) to water while translocating protons
      across the membrane. The enzyme hosts two copper and two heme iron moieties (heme
      a/heme a3). The atomic details of the sequential steps that go along with this
      redox-driven proton translocation are a matter of debate. Particularly for the
      reductive phase of CcO that precedes oxygen binding experimental data are scarce.
      Here, we use CcO under anaerobic conditions where carbon monoxide (CO) is bound
      to heme a3 which in tandem with CuB forms the binuclear center (BNC). Fourier
      transform infrared (FTIR) absorption spectroscopy is combined with electro
      chemistry to probe different redox and protonation states populated by variation
      of the external electrostatic potential. With this approach, the redox behavior
      of heme a and the BNC could be separated and the corresponding redox potentials
      were determined. We also infer the protonation of one of the propionate side
      chains of heme a3 to correlate with the oxidation of heme a. Experimental changes
      in the local electric field surrounding CO bound to heme a3 are determined by
      their vibrational Stark effect and agree well with electrostatic computations.
      The comparison of experimental and computational results indicates that changes
      of the heme a3/CuB redox state are coupled to proton transfer towards heme a3.
      The latter supports the role of the heme a3 propionate D as proton loading site.

PMID- 29067356
TI  - Cell-Specific RNA Binding Protein Rbfox2 Regulates CaV2.2 mRNA Exon Composition
      and CaV2.2 Current Size.
AB  - The majority of multiexon mammalian genes contain alternatively spliced exons
      that have unique expression patterns in different cell populations and that have
      important cell functions. The expression profiles of alternative exons are
      controlled by cell-specific splicing factors that can promote exon inclusion or
      exon skipping but with few exceptions we do not know which specific splicing
      factors control the expression of alternatively spliced exons of known biological
      function. Many ion channel genes undergo extensive alternative splicing including
      Cacna1b that encodes the voltage-gated CaV2.2 alpha1 subunit. Alternatively
      spliced exon 18a in Cacna1b RNA encodes 21 amino acids in the II-III loop of
      CaV2.2, and its expression differs across the nervous system and over
      development. Genome-wide, protein-RNA binding analyses coupled to high-throughput
      RNA sequencing show that RNA binding Fox (Rbfox) proteins associate with CaV2.2
      (Cacna1b) pre-mRNAs. Here, we link Rbfox2 to suppression of e18a. We show
      increased e18a inclusion in CaV2.2 mRNAs: (1) after siRNA knockdown of Rbfox2 in
      a neuronal cell line and (2) in RNA from sympathetic neurons of adult compared to
      early postnatal mice. By immunoprecipitation of Rbfox2-RNA complexes followed by
      qPCR, we demonstrate reduced Rbfox2 binding upstream of e18a in RNA from
      sympathetic neurons of adult compared to early postnatal mice. CaV2.2 currents in
      cell lines and in sympathetic neurons expressing only e18a-CaV2.2 are larger
      compared to currents from those expressing only Delta18a-CaV2.2. We conclude that
      Rbfox2 represses e18a inclusion during pre-mRNA splicing of CaV2.2, limiting the
      size of CaV2.2 currents early in development in certain neuronal populations.

PMID- 29067360
TI  - Distribution of aluminum over different T-sites in ferrierite zeolites studied
      with aluminum valence to core X-ray emission spectroscopy.
AB  - The potential of valence to core Al X-ray emission spectroscopy to determine
      aluminum distribution in ferrierite zeolites was investigated. The recorded
      emission spectra of four samples prepared with different structure directing
      agents exhibit slight variations in the position of the main emission peak and
      the intensity of its low energy shoulder. Theoretical calculations indicate that
      an increased intensity of the Kbetax shoulder in the Al emission spectra can be
      linked to a predominant occupation of the T3 site by a single aluminum atom. This
      study thus suggests that valence to core X-ray emission spectroscopy can be
      applied to help determine the occupation of aluminum at crystallographic T-sites
      in zeolites.

PMID- 29067361
TI  - A solution-based single-molecule study of surface-bound PBIs: solvent-mediated
      environmental effects on molecular flexibility.
AB  - We have investigated the fundamental photophysical properties of surface-bound
      perylene bisimide (PBI) molecules in a solution-phase at the single-molecule
      level. By efficient immobilization of single PBIs on glass, we were able to
      simultaneously monitor fluorescence intensity trajectories, fluorescence
      lifetimes, and emission spectra of individual PBIs in organic and aqueous media
      using confocal microscopy. We showed that the fluorescence dynamics of single
      PBIs in the solution phase is highly dependent on their local and chemical
      environments. Furthermore, we visualized different spatial-fluctuations of
      surface-bound PBIs using defocused wide-field imaging. While PBIs show more
      steric flexibility in organic media, the flexible motion of PBI molecules in
      aqueous solution is relatively prohibited due to a cage effect by a hydrogen
      bonding network, which is previously unobserved. Our method opens up a new
      possibility to investigate the photophysical properties of multi-chromophoric
      systems in various solvents at the single-molecule level for developing optimal
      molecular devices such as water-proof devices.

PMID- 29067362
TI  - Palladium-catalyzed C-H activation/C-C cross-coupling reactions via
      electrochemistry.
AB  - Palladium-catalyzed C-H activation/C-C cross-coupling reactions typically require
      stoichiometric chemical oxidants and exogenous ligands. However, there are
      significant disadvantages associated with the use of traditional stoichiometric
      oxidants. To overcome these issues, we have developed an electrochemical strategy
      to achieve methylation and acylation.

PMID- 29067363
TI  - Rational control of the interlayer space inside two-dimensional titanium carbides
      for highly efficient uranium removal and imprisonment.
AB  - Though two-dimensional early transition metal carbides and carbonitrides (MXenes)
      have attracted extensive interest recently, their superb abilities in various
      scientific applications always suffer from the very narrow interlayer space
      inside the multilayered structure. Here we demonstrate an unprecedented large
      adsorption capacity enhancement of Ti3C2Tx toward radionuclide removal via a
      hydrated intercalation strategy. By rational control of the interlayer space, the
      potential for imprisoning the representative actinide U(vi) inside multilayered
      Ti3C2Tx was also confirmed.

PMID- 29067364
TI  - Design of an efficient coherent multi-site single-molecule rectifier.
AB  - We propose the design of a single-molecule diode with a rectification ratio
      exceeding a million. The employed mechanism is based on coherent resonant charge
      transport across a molecule that consists of four conjugated sites coupled by non
      conjugated bridges. Using density functional theory calculations, we rationalize
      the design of the molecule and demonstrate the crucial role of aligning the sites
      at a specific voltage. Rectification ratios are calculated for a series of
      chemical substituents and demonstrate that with careful molecular design, high
      rectification ratios can be achieved. Finally, we comment on the shortcomings of
      our approach, how further improvements can be obtained and discuss some of the
      experimental challenges.

PMID- 29067366
TI  - Control of reactivity through chemical order in very small RuRe nanoparticles.
AB  - The choice of suitable organometallic precursors, [Re2(C3H5)4] and [Ru(Me
      Allyl)2COD] or [Ru(COD)(COT)], allows us to synthesize polyvinylpyrrolidone (PVP)
      stabilized bimetallic RuRe nanoparticles of ca. 1.3 nm with narrow size
      dispersity, displaying the hcp crystal structure and to control their chemical
      order: an alloy or Re rich surface. The structural features of these NPs were
      determined using complementary characterization techniques (TEM, HRTEM, STEM
      HAADF, EDX, WAXS, FT-IR, MAS-NMR and ICP). In particular, surface state
      investigation based on CO adsorption and oxidation reactions provided useful
      information of the chemical order in these nanoparticles. The RuRe NPs were
      obtained as stable colloidal solutions or powders. Surface reactivity studies
      demonstrated that the alloy type RuRe/PVP NPs show better resistance to oxidation
      than the ones displaying a Re enriched surface and are more active towards CO
      dissociation than monometallic Re/PVP NPs as a result of the synergic effect
      between Ru and Re. Interestingly, the dissociation of CO was not observed with
      RuRe/PVP NPs displaying a Re enriched surface. Besides the synthetic aspect, this
      work highlights the crucial influence of the chemical order resulting from the
      choice of the metal sources in the control of the reactivity of ultra-small metal
      nanoparticles.

PMID- 29067365
TI  - Perdeuterated and 13C-enriched myo-inositol for DNP assisted monitoring of
      enzymatic phosphorylation by inositol-3-kinase.
AB  - The synthesis of perdeuterated and 13C enriched myo-inositol is presented. Myo
      inositol and its derivatives are of interest as substrates for enzymes producing
      phosphorylated species with regulatory functions in many organisms. Its utility
      in monitoring real-time phosphorylation by myo-inositol-3-kinase is illustrated
      using dynamic nuclear polarization (DNP) to enhance NMR observation.

PMID- 29067367
TI  - A general method for the inclusion of radiation chemistry in astrochemical
      models.
AB  - In this paper, we propose a general formalism that allows for the estimation of
      radiolysis decomposition pathways and rate coefficients suitable for use in
      astrochemical models, with a focus on solid phase chemistry. Such a theory can
      help increase the connection between laboratory astrophysics experiments and
      astrochemical models by providing a means for modelers to incorporate radiation
      chemistry into chemical networks. The general method proposed here is targeted
      particularly at the majority of species now included in chemical networks for
      which little radiochemical data exist; however, the method can also be used as a
      starting point for considering better studied species. We here apply our theory
      to the irradiation of H2O ice and compare the results with previous experimental
      data.

PMID- 29067368
TI  - Chemoselective guest-triggered shaping of a polynuclear CuII calix[6]complex into
      a molecular host.
AB  - A new calix[6]arene scaffold bearing a tris-imidazole binding site at the small
      rim and three tetradentate aza ligands at the large rim was synthesized. The
      system binds three CuII ions at the large rim sites and is unable to bind a
      fourth one, which remains in solution. The charge repulsion between the
      complexes, together with the flexibility of the scaffold, disorganizes the small
      rim site for binding and prevents its use for host-guest studies. Although the
      presence of MeCN or DMF guests does not alter this state, the addition of a
      heptylamine guest, which further displays Bronsted basicity, restores its
      receptor ability by stabilizing the extra CuII ion at the tris-imidazole site
      with concomitant guest encapsulation and binding of an exo hydroxo ligand. This
      chemoselective nuclearity switch yields a tetranuclear complex in which the guest
      backbone is preorganized in front of three potentially reactive Cu(ii) complexes,
      reminiscent of polynuclear CuII enzyme active sites.

PMID- 29067369
TI  - ortho-Cycloalkyl substituted N,N'-diaryliminoacenaphthene-Ni(ii) catalysts for
      polyethylene elastomers; exploring ring size and temperature effects.
AB  - A family of six unsymmetrical N,N'-diiminoacenaphthene-nickel(ii) bromide
      complexes, [1-{2,6-(Ph2CH)2-4-MeC6H2N}-2-(ArN)C2C10H6]NiBr2 (Ar = 2-(C6H11)-6
      MeC6H2Ni1, 2-(C5H9)-6-MeC6H2Ni2, 2-(C8H15)-6-MeC6H2Ni3, 2-(C6H11)-4,6-Me2C6H2Ni4,
      2-(C5H9)-4,6-Me2C6H2Ni5, 2-(C8H15)-4,6-Me2C6H2Ni6), each bearing one ring-size
      variable 4-R-2-methyl-6-cycloalkyl-substituted N-aryl group and one N'-4-methyl
      2,6-dibenzhydrylphenyl group, have been prepared and fully characterized. The
      molecular structures of Ni1, Ni2, Ni3 and Ni5 reveal distorted tetrahedral
      geometries with different degrees of steric protection imparted by the two
      inequivalent N-aryl groups. On activation with either EASC or MMAO, all the
      precatalysts are highly active (up to 17.45 * 106 g PE mol-1 (Ni) h-1) for
      ethylene polymerization at 20-50  degrees C with their activities correlating
      with the type of cycloalkyl ortho-substituent: cyclooctyl (Ni6, Ni3) > the
      cyclopentyl (Ni5, Ni2) > cyclohexyl (Ni4, Ni1) for either R = H or Me. Moderately
      branched to hyperbranched polyethylenes (Tm's as low as 44.2  degrees C) can be
      obtained with molecular weights in the range 2.14-6.68 * 105 g mol-1 with the
      branching content enhanced by the temperature of the polymerization. Dynamic
      mechanical analysis (DMA) and monotonic tensile stress-strain tests have been
      employed on the polyethylene samples and reveal the more branched materials to
      show good elastic recovery properties (up to 75.5%).

PMID- 29067370
TI  - Catechol-cation adhesion on silica surfaces: molecular dynamics simulations.
AB  - Understanding the interaction mechanism between catechol-cation and inorganic
      surfaces is vital for controlling the interfacial adhesion behavior. In this
      work, molecular dynamics simulations are employed to study the adhesion of
      siderophore analogues (Tren-Lys-Cam, Tren-Arg-Cam and Tren-His-Cam) on silica
      surfaces with different degrees of ionization and the effects of cationic amino
      acids and ionic strength on adhesion are discussed. Simulation results indicate
      that adhesion of catechol-cation onto the ionized silica surface is dominated by
      electrostatic interactions. At different degrees of ionization, the rank of the
      adhesions of three siderophore analogues on silica is different. Further analysis
      shows that the amino acid terminus has a large influence on the adhesion process,
      especially histidine adhesion on negatively charged surfaces. Tren-Lys-Cam (TLC)
      has a larger adhesion free energy than Tren-Arg-Cam (TAC) at a higher degree of
      ionization (18%); both the bulkier structure and delocalized charge of Arg
      decreased the cation's electrostatic interaction with the charged silica. In
      addition, the adhesion free energy on ionized silica surfaces decreased with
      increasing ionic strength of aqueous solutions. A linear correlation between the
      potential of mean force obtained from umbrella sampling and the rupture force via
      steered molecular dynamics simulations for siderophore analogue adhesion on
      silica surfaces is also found. This work may provide some guidance for developing
      the next generation underwater adhesives.

PMID- 29067371
TI  - A ring polymer molecular dynamics study of the OH + H2(D2) reaction.
AB  - In this work we have performed a ring polymer molecular dynamics (RPMD) study of
      the OH + H2 and OH + D2 reactions at temperatures ranging from 150 K to 2000 K
      using two available ab initio potential energy surfaces (PESs) that have been
      termed as the YZCL2 and NN1 PES, respectively. The YZCL2 PES was developed by
      Yang et al. [J. Chem. Phys., 2001, 115(1), 174] which is based on points fitted
      by a modified Shephard interpolation method and calculated with unrestricted
      coupled-cluster theory with all single and double excitations and a perturbative
      account of the triple excitations (UCCSD(T)) method with an aug-cc-pVQZ basis.
      The NN1 PES was constructed by Chen et al. [J. Chem. Phys., 2013, 138(15),
      154301] using a neural networks method to fit ab initio energies calculated at
      the UCCSD(T)-F12a/AVTZ level of theory. We show that both techniques provide
      reliable PESs. The RPMD thermal rate coefficients and the kinetic isotope effects
      (KIEs) calculated using these two PESs are in very good agreement with each other
      as well as with previous experimental values available to date. Besides, we have
      shown that these two procedures for fitting PESs can yield even more similar RPMD
      rate coefficients when the same level of ab initio theory is employed, at least
      for the present OH + H2 reaction. Comparison of the previous theoretical
      calculations on the NN1 PES, namely, instanton theory and canonical variational
      theory with microcanonical optimized multidimensional tunneling, shows that the
      present RPMD results are more consistent and accurate. Future experimental
      measurements of the KIEs and accurate quantum mechanical calculations on these
      PESs are highly desirable, especially at low temperatures.

PMID- 29067372
TI  - Stratification and two glass-like thermal transitions in aged polymer films.
AB  - Using X-ray reflectivity, spectroscopic ellipsometry and Raman spectroscopy, we
      have studied the stratified structure and the two glass-like thermal transitions
      in sufficiently aged glassy polystyrene films. We find that favorable interaction
      between the solid substrate and the polymer film induces stratification within
      the film resulting in different densities across the film thickness. Existence of
      two glass-like thermal transitions (one at 70  degrees C and the other at 95 
      degrees C) is independently confirmed by temperature dependent spectroscopic
      ellipsometry and Raman spectroscopy measurements. Interestingly, the thermal
      coefficient of expansion of the polymer film displays anomalous behavior with
      temperature and is found to have the lowest value over the temperature range 70
      95  degrees C, i.e. between the two observed glass-like thermal transition
      temperatures.

PMID- 29067373
TI  - Adsorption and dissociation of O2 on MoO2(1[combining macron]11) surfaces: a DFT
      study.
AB  - The adsorption and dissociation of O2 on MoO2(1[combining macron]11) surfaces
      were studied by density functional theory (DFT). The results show that O2
      molecules prefer to be adsorbed on the five-coordinated Mo top sites. Density of
      states analysis shows strong hybridization of Mo 4d orbitals and O 2p orbitals in
      the Mo-O bond. Clean MoO2 slabs and slabs with O2 adsorption are metallic
      conductors, whereas the surface with high O atom coverage is reconstructed and
      becomes a semiconductor. Surface Mo atoms without adsorbed O or O2 are spin
      polarized. The oxygen adsorption shows the ability to reduce the spin of surface
      Mo atoms. The adsorption energy of the O2 and O atoms decreases as coverage
      increases. The transition states of O2 dissociation were located. The energy
      barriers for O2 dissociation on the five-coordinated and four-coordinated Mo top
      sites are 0.227 eV and 0.281 eV, respectively.

PMID- 29067375
TI  - A mechanistic study of nitrite reduction on iron(ii) complexes of methylated N
      confused porphyrins.
AB  - Proton delivery to the prosthetic group is a crucial step to sustain the activity
      of nitrite reductase. An iron N-confused porphyrin (NCP) complex, which is
      capable of relaying protons from the outer pyrrolic nitrogen (Nout-H) of the
      inverted pyrrole ring to the axial coordinated ligand, has been demonstrated to
      facilitate facile nitrite reduction. Time-dependent FTIR studies on the reaction
      between [FeII(HCTPPMe)Br] (1) and a nitrite anion revealed a two-step process
      involving conversion of the starting complex 1 to an {Fe(NO)}7 intermediate,
      [Fe(CTPPMe)(NO)] (5), before the detection of [Fe(CTPPCH2)(NO)] (3), an {Fe(NO)}6
      end product. Moreover, spectroscopic data confirm that Nout-H on the NCP core is
      indispensable to the proceeding of the nitrite reduction reaction. Mass spectra
      have detected the coordination of a nitrite to the iron center while DFT
      theoretical calculations suggest that subsequent intramolecular proton transfer
      to a nitro group to form [Fe(CTPPMe)(HNO2)] (6a) evokes a homolytic N-OH bond
      fission on axial nitrous acid due to an enhanced pi-back-bonding to produce an
      {Fe(NO)}7 intermediate and to release a hydroxyl radical. The subsequent
      oxidation of an {Fe(NO)}7 intermediate by the hydroxyl radical gave the final
      product, {Fe(NO)}6 [Fe(CTPPCH2)(NO)] (3). This study illustrates a proton
      assisted small molecule activation on the iron N-confused porphyrin coordination
      sphere and provides complemental insights into the mechanism of enzymatic nitrite
      reduction reactions.

PMID- 29067374
TI  - Degradable and biocompatible hydrogels bearing a hindered urea bond.
AB  - A hindered urea bond (HUB), recently reported as a new type of dynamic chemical
      bond, can be facilely constructed by mixing an isocyanate and a hindered amine.
      Here, we report the use of the HUB in the design of degradable hydrogel materials
      for applications of stem cell encapsulation and delivery. Polyethyleneglycol
      (PEG) diamine was end-capped with a HUB and an allyl group in a one-pot
      synthesis. The resulting polymer was cross-linked to form a hydrogel under UV
      with the addition of a 4-arm PEG thiol and a photoinitiator. The degradation
      properties of the hydrogels were confirmed with NMR, GPC, weight loss, and
      protein release studies. We found that the degradation kinetics is dependent on
      the size of the N-substituents, and the one with the tert-butyl group shows
      complete degradation within 2 days. The new hydrogel materials were also
      demonstrated to be biocompatible with hMSCs, and the cell release kinetics can be
      facilely tuned over 5 days.

PMID- 29067376
TI  - Facile synthesis of a SiOx/asphalt membrane for high performance lithium-ion
      battery anodes.
AB  - Herein, a novel SiOx/asphalt membrane was facilely synthesized via
      demulsification of porous SiOx microspheres. After high temperature pyrolysis,
      SiOx/carbon composites not only could function as binder-free anodes, but could
      also exhibit excellent cycling stability and high initial Coulombic efficiency as
      anodes for practical application.

PMID- 29067378
TI  - Band-edge engineering via molecule intercalation: a new strategy to improve
      stability of few-layer black phosphorus.
AB  - The poor environmental stability of black phosphorous (BP) seriously limits its
      practical applications in (opto)electronics. Other than capping protective layers
      on its surface, herein we propose a new strategy to improve BP's ambient
      stability by engineering the interlayer interactions. Our first-principles
      calculations demonstrate that enlarging the interlayer spacing can effectively
      shift the conduction band minimum down to suppress the generation of superoxide
      and the enlargement can be achieved by intercalating small molecules like H2 and
      He into BP. Moreover, the molecule intercalated BP maintains high hole mobility,
      which makes it a better two-dimensional semiconductor for practical applications.

PMID- 29067377
TI  - Development of a soy protein isolate-carrageenan-quercetagetin non-covalent
      complex for the stabilization of beta-carotene emulsions.
AB  - The current study investigated the application of a soy protein isolate (SPI),
      kappa-carrageenan (CG) and quercetagetin (Qut) non-covalent complex in
      stabilizing beta-carotene emulsions. The ternary complex was formed through a
      mild mixing and incubation process. FTIR measurement indicated the formation of
      hydrogen bonds in the non-covalent complex. SPI-CG and SPI-CG-Qut complexes had a
      much smaller particle size when redispersed in water after spray drying, compared
      to those in the original dispersions (p < 0.05). Dynamic light scattering
      analysis revealed that the emulsion stabilized with the ternary complex had a
      bigger particle size, higher surface charge, and improved creaming stability
      compared to those stabilized with SPI or SPI-Qut (p < 0.05). The ternary complex
      allowed less degradation of beta-carotene in the emulsions when exposed to light
      or thermally treated at 37  degrees C or 55  degrees C. Therefore, the SPI-CG-Qut
      non-covalent complex might work as a novel ingredient in designing delivery
      systems for beta-carotene.

PMID- 29067379
TI  - An unusual zig-zag 1D copper(ii) coordination polymer displaying magnetic phase
      transition.
AB  - An unusual Cu(ii) coordination polymer [Cu(Him)2(L)] (1) having a 4,4'-{[1,2
      phenylene bis-(methylene)]bis(oxy)}dibenzoic acid ligand and an imidazole ligand
      possessing a 1D zig-zag chain was constructed and its magnetic behaviour was
      investigated, which indicated a magnetic phase transition below 25 K as well as
      long-range magnetic ordering.

PMID- 29067380
TI  - d-Serine enzymatic metabolism induced formation of a powder-remoldable PAAM-CS
      hydrogel.
AB  - The metabolism of d-serine by d-amino acid oxidase was developed to induce
      radical polymerization and formation of a powder-remoldable PAAM-CS hydrogel.

PMID- 29067381
TI  - Magnetic-field-induced synthesis of magnetic wire-like micro- and nanostructures.
AB  - A lot of physical and chemical preparation methods of one-dimensional (1D)
      structures are known today. Most of them use highly advanced technology or quite
      complex chemical reagents. This results in their high costs and difficulties with
      their implementation to a large industrial scale. Hence, new, facile and
      inexpensive approaches are still sought. One alternative to wire-like structure
      production is based on the chemical reduction reactions combined with an external
      magnetic field, which acts as an independent synthesis parameter. This approach
      is commonly called magnetic-field-assisted (MFA) synthesis or magnetic-field
      induced (MFI) synthesis. As usual, this manufacturing strategy comprises both
      drawbacks and advantages, which are introduced in this review. Moreover, this
      work shows that MFI synthesis depends on several synthesis parameters including
      the strength of the applied magnetic field, reaction temperature, pH value of the
      reaction environment, chemical composition of the precursor solution, reaction
      time, and also the presence of surfactants, complexing agents, nucleating agents,
      initiators as well as organic solvents. All of them have an impact on the
      morphology and dimensions of wire-like materials and their chemical, physical and
      mechanical properties. Finally, the opportunities and challenges associated with
      the magnetic-assisted fabrication of wire-like structures are widely discussed in
      this review.

PMID- 29067382
TI  - Extreme halophilic alcohol dehydrogenase mediated highly efficient syntheses of
      enantiopure aromatic alcohols.
AB  - Enzymatic synthesis of enantiopure aromatic secondary alcohols (including
      substituted, hetero-aromatic and bicyclic structures) was carried out using
      halophilic alcohol dehydrogenase ADH2 from Haloferax volcanii (HvADH2). This
      enzyme showed an unprecedented substrate scope and absolute enatioselectivity.
      The cofactor NADPH was used catalytically and regenerated in situ by the
      biocatalyst, in the presence of 5% ethanol. The efficiency of HvADH2 for the
      conversion of aromatic ketones was markedly influenced by the steric and
      electronic factors as well as the solubility of ketones in the reaction medium.
      Furthermore, carbonyl stretching band frequencies nu (C[double bond, length as m
      dash]O) have been measured for different ketones to understand the effect of
      electron withdrawing or donating properties of the ketone substituents on the
      reaction rate catalyzed by HvADH2. Good correlation was observed between nu
      (C[double bond, length as m-dash]O) of methyl aryl-ketones and the reaction rate
      catalyzed by HvADH2. The enzyme catalyzed the reductions of ketone substrates on
      the preparative scale, demonstrating that HvADH2 would be a valuable biocatalyst
      for the preparation of chiral aromatic alcohols of pharmaceutical interest.

PMID- 29067384
TI  - Wide-spectral/dynamic-range skin-compatible phototransistors enabled by floated
      heterojunction structures with surface functionalized SWCNTs and amorphous oxide
      semiconductors.
AB  - Purified semiconducting single-walled carbon nanotubes (sc-SWCNTs) have been
      researched for optoelectronic applications due to their high absorption
      coefficient from the visible to even the near-infrared (NIR) region.
      Nevertheless, the insufficient electrical characteristics and incompatibility
      with conventional CMOS processing have limited their wide utilization in this
      emerging field. Here, we demonstrate highly detective and wide spectral/dynamic
      range phototransistors incorporating floated heterojunction active layers which
      are composed of low-temperature sol-gel processed n-type amorphous indium gallium
      zinc oxide (a-IGZO) stacked with a purified p-type sc-SWCNT layer. To achieve a
      high and broad spectral/dynamic range photo-response of the heterogeneous
      transistors, photochemically functionalized sc-SWCNT layers were carefully
      implemented onto the a-IGZO channel area with a floating p-n heterojunction
      active layer, resulting in the suppression of parasitic charge leakage and good
      bias driven opto-electrical properties. The highest photosensitivity (R) of 9.6 *
      102 A W-1 and a photodetectivity (D*) of 4 * 1014 Jones along with a dynamic
      range of 100-180 dB were achieved for our phototransistor in the spectral range
      of 400-780 nm including continuous and minimal frequency independent behaviors.
      More importantly, to demonstrate the diverse application of the ultra-flexible
      hybrid photosensor platform as skin compatible electronics, the sc-SWCNT/a-IGZO
      phototransistors were fabricated on an ultra-thin (~1 MUm) polyimide film along
      with a severe static and dynamic electro-mechanical test. The skin-like
      phototransistors showed excellent mechanical stability such as sustainable good
      electrical performance and high photosensitivity in a wide dynamic range without
      any visible cracks or damage and little noise interference after being rolled-up
      on the 150 MUm-thick optical fiber as well as more than 1000 times cycling.

PMID- 29067385
TI  - Deformation of the contact line around spherical particles bound at anisotropic
      fluid interfaces.
AB  - When a particle adsorbs at a liquid interface, the 3-phase contact line geometry
      depends on the shape of the particle and of the liquid interface. The shape of
      the contact line is the key to controlling capillary forces among particles, and
      is therefore a useful means to direct assembly of interfacial particles. We
      measured the shape of the contact line around millimeter-sized PDMS-coated glass
      spheres at water/air interfaces with anisotropic shapes. We studied the advancing
      and receding conditions separately. We focused on interfaces with a cylindrical
      shape, where the predominant deformation of the meniscus and the contact line
      both have quadrupolar cos(2phi) symmetry. We related the measured magnitude of
      the quadrupolar deformation to the applied vertical force on the sphere and the
      interface's deviatoric curvature, D0. For modest curvature (D0 < 0.1 * sphere
      radius), our results agree with the theoretical prediction for free particles. At
      higher curvature, the measurements exceed the theory. The theory appears to apply
      even when there is contact-angle hysteresis, as long as the measured contact
      angle is used rather than the equilibrium (Young-Dupre) angle. The magnitude of
      the quadrupolar deformation depends on the applied force. Together, these results
      show the range of validity of the theory.

PMID- 29067383
TI  - Integrated microHall magnetometer to measure the magnetic properties of
      nanoparticles.
AB  - Magnetic nanoparticles (MNPs) are widely used in biomedical and clinical
      applications, including medical imaging, therapeutics, and biological sample
      processing. Rapid characterization of MNPs, notably their magnetic moments,
      should facilitate optimization of particle synthesis and accelerate assay
      development. Here, we report a compact and low-cost magnetometer for fast, on
      site MNP characterization. Termed integrated microHall magnetometer (iHM), our
      device was fabricated using standard semiconductor processes: an array of Hall
      sensors, transistor switches, and amplifiers were integrated into a single chip,
      thus improving the detection sensitivity and facilitating chip operation. By
      applying the iHM, we demonstrate versatile magnetic assays. We measured the
      magnetic susceptibility and moments of MNPs using small sample amounts (~10 pL),
      identified different MNP compositions in mixtures, and detected MNP-labeled
      single cells.

PMID- 29067386
TI  - Tuning the collective switching behavior of azobenzene/Au hybrid materials:
      flexible versus rigid azobenzene backbones and Au(111) surfaces versus curved Au
      nanoparticles.
AB  - The combination of photo-responsive azobenzene (AB) and biocompatible Au
      nanomaterials possesses potential applications in diverse fields such as
      biosensing and thermotherapy. To explore the influence of azobenzene moieties and
      Au substrates on the collective switching behavior, two different azobenzene
      derivatives (rigid biphenyl-controlled versus flexible alkoxyl chain-linked) and
      three different Au substrates (a planar Au(111) surface, curved Au102(SR)44 and
      Au25(SR)18 clusters) were chosen to form six Au@AB combinations. A reactive
      molecular dynamics (RMD) model considering both the torsion and inversion path
      was implemented to simulate the collective photo-induced cis-to-trans switching
      process of AB monolayers on Au substrates. The major driving force for
      isomerization is demonstrated to be the torsion of the C-N[double bond, length as
      m-dash]N-C dihedral angle, in addition to the minor contribution from an
      inversion pathway. The isomerization process can be divided into the preliminary
      conformation switching stage and the later relaxation stage, in which a gradual
      self-organization is observed for 40 ps. The Au substrate affects the packing
      structure of the AB monolayer, while the choice of different kinds of ABs tunes
      the intermolecular interaction in the monolayer. Flexible alkoxyl-linked F-AB may
      achieve much faster conversion on Au clusters than on the surface. For rigid
      biphenyl-based R-AB anchored on Au nanoparticles (AuNPs), a competitive torsion
      between the biphenyl and C-N[double bond, length as m-dash]N-C dihedral may delay
      the C-N[double bond, length as m-dash]N-C dihedral torsion and the following
      isomerization process. After the R-AB molecules were anchored on the Au(111)
      surface, the strong pi-pi stacking between biphenyl units accelerates the
      collective isomerization process. A curvature-dependent effect is observed for R
      AB SAMs on different-sized substrates. The cooperation between functional AB
      monolayers and the Au substrate determines the collective switching behavior of
      Au@AB materials. These results are expected to guide rational designs of Au@AB
      hybrid materials for different uses.

PMID- 29067387
TI  - Calcium carbonate with nanogranular microstructure yields enhanced toughness.
AB  - The presence of nanogranular microstructures is a widely reported feature of
      biominerals that form by classical and non-classical mineralization pathways.
      Inspired by nature, we have synthesized amorphous calcium carbonate nanoparticles
      with nanogranular microstructures, whose grain size is tuned by varying the
      polymer concentration. The response to indentation of single calcium carbonate
      nanoparticles proceeds via an intermittent stick-slip that reflects the
      characteristics of the nanogranular microstructure. A two-fold mechanism is thus
      proposed to enhance the toughness of the nanoparticles, namely nanogranular
      rearrangement and intergranular bridging by an organic phase and/or hydration.
      This work not only provides a synthesis route to design biologically inspired
      mineral nanoparticles with nanogranular structure, but also helps in
      understanding toughening mechanisms of biominerals arising from their nanoscale
      heterogeneity.

PMID- 29067388
TI  - Soluble soybean polysaccharides enhance the protective effects of genistein
      against hepatic injury in high l-carnitine-fed mice.
AB  - This study was to develop a novel strategy for the simultaneous consumption of
      soluble soybean polysaccharides (SSPS) to enhance the absorption of genistein and
      its protective effects against high l-carnitine-induced hepatic injury in mice.
      UPLC-qTOP/MS measurements showed that SSPS observably increased the urinary
      concentration of genistein and its metabolites in mice. The mice fed with 3% l
      carnitine water for 12 weeks experienced a disturbance of the hepatic lipid
      metabolism, oxidative stress and inflammation, which was evidenced by abnormal
      TC, LDL, RAHFR and MDA levels, unusual AST, ALT, ALP, SOD and GSP-Px activities,
      and increased IF-1, IF-6 and TNF-alpha expressions. Interestingly, the co
      supplementation of SSPS and genistein was capable of regulating these imbalances
      more effectively than the administration of SSPS or genistein alone, which was
      also confirmed by histological observations of the mouse liver. These findings
      suggest that the co-ingestion of SSPS and genistein is a feasible strategy for
      improving liver protection in mice.

PMID- 29067389
TI  - Accumulation of counterions and coions evaluated by cryogenic XPS as a new tool
      for describing the structure of electric double layer at the silica/water
      interface.
AB  - We introduce a new method of evaluating the structure of electric double layer
      (EDL) at the native solid/liquid interface using cryogenic X-ray photoelectron
      spectroscopy technique. This method is based on evaluating the atomic
      concentration ratio of counterions and co-ions of supporting electrolyte at the
      close-to-in situ state surface of colloid particles by the cryo-XPS and comparing
      it with analogous ratio predicted by EDL models. For silica colloids in aqueous
      KCl solutions at pH 6 to 8 it has been found that the latter ratio is higher than
      unity, as expected for the negatively charged surface of silica, but does not
      correspond with the prediction of the basic Gouy-Chapman EDL model for the ideal
      interface. However, it agrees with that deduced from experiments on electrolytic
      coagulation kinetics of analogous silica colloids by applying a simple EDL model
      of swellable ion-permeable (Donnanian) polyelectrolyte gel layer. It turns out
      that the traditional Stern layer-based concept of EDL at solid/liquid interfaces
      is not justified for metal oxides at least in KCl solutions.

PMID- 29067390
TI  - Successive energy transfer within multiple photosensitizers assembled in a
      hexameric hemoprotein scaffold.
AB  - An assembly of multiple photosensitizers is demonstrated by development of a
      hexameric hemoprotein (HTHP) scaffold as a light harvesting model to replicate
      the successive energy transfer occuring within photosensitizer assemblies of
      natural systems. In our model, six zinc protoporphyrin IX (ZnPP) molecules are
      arrayed at the heme binding site of HTHP by supramolecular interactions and five
      fluorescein (Flu) molecules and one Texas Red (Tex) molecule as donor and
      acceptor photosensitizers, respectively, are attached to the HTHP protein surface
      with covalent linkages. The flow of excited energy from photoexcited Flu to Tex
      occurs via two pathways: direct energy transfer from Flu to Tex (path 1) and
      energy transfer via ZnPP (path 2). Steady state and time-resolved fluorescence
      measurements reveal that the energy transfer ratio of these pathways (path 1 :
      path 2) is 39 : 61. These findings indicate that the excited energy originating
      at five Flu and six ZnPP molecules is collected at one Tex molecule as a funnel
      like bottom for light harvesting. The present system using the hexameric
      hemoprotein scaffold is a promising candidate for construction of an artificial
      light harvesting system having multiple photosensitizers to promote efficient use
      of solar energy.

PMID- 29067391
TI  - In situ growth of gold nanoparticles on Hg2+-binding M13 phages for mercury
      sensing.
AB  - Mercury poses a serious threat to human health and the ecosystem. Its pollution
      is still prevalent in developing areas, which calls for the development of a
      simple on-site method for Hg2+ detection. Plasmonic nanosensors for mercury,
      especially those based on gold nanoparticles (AuNPs), have been increasingly
      developed due to the flourish of nanotechnology in the last decade. However, the
      limitation on either selectivity or stability hindered their practical
      applications. Herein, by taking advantage of the unique optical properties of
      AuNPs and the versatility of M13 phages, a novel Hg2+ sensing strategy is
      proposed. AuNPs grew in situ on the surface of Hg2+-binding M13 phages at room
      temperature and the resulting AuNP-phage networks were directly used for mercury
      sensing. Hg2+ was selectively captured by M13 phages indwelling in the networks
      and gathered around AuNPs, followed by the reduction into Hg(0) and deposition on
      the AuNP surfaces, wherein it resulted in a blue shift of the SPR band of AuNPs
      and an increase in the absorbance. An LOD of 8 * 10-8 mol L-1 was achieved based
      on the quantification of the absorption ratio of AuNPs at 525 and 650 nm. As the
      Hg2+ recognition was double guaranteed by the capture of Hg2+-binding phages as
      well as the unique affinity between mercury and gold, the sensing system showed a
      high selectivity and a superior interference tolerance capability, facilitating
      its practical applications in environmental water bodies without deterioration of
      the sensing performance.

PMID- 29067392
TI  - Luminescence tuning and exciton dynamics of Mn-doped CsPbCl3 nanocrystals.
AB  - Mn-Doped perovskite nanocrystals (NCs) are a new class of materials offering
      exciting opportunities to control over their optical and magnetic properties.
      Herein, we report a series of Mn-doped CsPbCl3 NCs exhibiting a tunable Mn
      photoluminescence (PL) band with a PL peak wavelength pushed up to 625 nm and
      tuned over a range of 40 nm, the largest achieved so far, by only varying the Mn
      content. The X-band EPR data and Mn PL decay behaviour of the NCs reveal that the
      exchange interaction between Mn2+ ions is mainly responsible for a large shift of
      the Mn PL band. Ultrafast pump-probe measurements show that exciton-dopant energy
      transfer in these NCs is slower (~50-100 ps) than trapping of the carriers (~8-10
      ps) in the host lattice. The large PL tuning reported here along with the
      insights into the mechanism of tuning and carrier dynamics are expected to boost
      the potential of Mn-doped CsPbCl3 NCs in light-powered devices.

PMID- 29067393
TI  - pH-Responsive self-assembly of cationic surfactants with a star-shaped tetra
      carboxylate acid and the solubilization of hydrophobic drugs.
AB  - This work involved the construction of pH-responsive self-assembly systems from a
      pH-sensitive four-arm carboxylate acid (4EOCOOH) and either the cationic single
      chain surfactant dodecyl trimethyl ammonium bromide (DTAB) or the cationic gemini
      surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12). It
      was found that the constructed oligomeric-like structures from the mixtures of
      4EOCOOH with DTAB or 12-6-12 greatly enhance the aggregation ability of the
      mixtures, thus improving the pH-responsivity. In particular, surfactant
      concentrations significantly affect the pH-responsivity at a fixed 4EOCOOH
      concentration. At higher surfactant concentrations, the pH-responsivity is
      suppressed, while at lower surfactant concentrations, the mixed aggregates
      gradually change from micelles to unstable large spherical aggregates or
      vesicles, and then to stable spherical aggregates, with decreasing pH. Moreover,
      the surfactant/4EOCOOH systems have different solubilization abilities for three
      hydrophobic drugs. For quercetin and baicalein, the systems support much better
      solubilization at lower pH values, while for indomethacin, the systems show
      better solubilization at higher pH values. In particular, compared with DTAB, 12
      6-12 is more efficient in constructing pH-responsive systems, and the 12-6
      12/4EOCOOH mixture shows better ability for solubilizing hydrophobic drugs. This
      work will be helpful in the design of high-efficiency, pH-responsive surfactant
      systems for solubilizing hydrophobic drugs by simply mixing pH-sensitive
      molecules with surfactants.

PMID- 29067394
TI  - A simple neridronate-based surface coating strategy for upconversion
      nanoparticles: highly colloidally stable 125I-radiolabeled NaYF4:Yb3+/Er3+@PEG
      nanoparticles for multimodal in vivo tissue imaging.
AB  - In this report, monodisperse upconversion NaYF4:Yb3+/Er3+ nanoparticles with
      superior optical properties were synthesized by the oleic acid-stabilized high
      temperature co-precipitation of lanthanide chlorides in octadec-1-ene as a high
      boiling organic solvent. To render the particles with biocompatibility and
      colloidal stability in bioanalytically relevant phosphate buffered saline (PBS),
      they were modified by using in-house synthesized poly(ethylene glycol)
      neridronate (PEG-Ner), a bisphosponate. The NaYF4:Yb3+/Er3+@PEG nanoparticles
      showed excellent long-term stability in PBS and/or albumin without any
      aggregation or morphology transformation. The in vitro cytotoxicity of the
      nanoparticles was evaluated using primary fibroblasts (HF) and a cell line
      derived from human cervical carcinoma (HeLa). The particles were subsequently
      modified by using Bolton-Hunter-hydroxybisphosphonate to enable radiolabeling
      with 125I for single-photon emission computed tomography/computed tomography
      (SPECT/CT) bimodal imaging to monitor the biodistribution of the nanoparticles in
      non-tumor mice. The bimodal upconversion 125I-radiolabeled NaYF4:Yb3+/Er3+@PEG
      nanoparticles are prospective for near-infrared (NIR) photothermal/photodynamic
      and SPECT/CT cancer theranostics.

PMID- 29067396
TI  - Phonon-mediated superconductivity in Mg intercalated bilayer borophenes.
AB  - Using first-principles calculations, we investigate the structural, electronic
      and superconducting properties of Mg intercalated bilayer borophenes BxMgBx (x =
      2-5). Remarkably, B2MgB2 and B4MgB4 are predicted to exhibit good phonon-mediated
      superconductivity with a high transition temperature (Tc) of 23.2 K and 13.3 K,
      respectively, while B4MgB4 is confirmed to be more practical based on the
      analyses of its stability. The densities of states of in-plane orbitals at the
      Fermi level are found to be dominant at the superconducting transition
      temperature in Mg intercalated bilayer borophenes, providing an effective avenue
      to explore Mg-B systems with high Tcs.

PMID- 29067395
TI  - Toward inert paramagnetic Ni(ii)-based chemical exchange saturation transfer MRI
      agents.
AB  - The Ni2+ complexes with hexadentate ligands containing two 6-methylpicolinamide
      groups linked by ethane-1,2-diamine (dedpam) or cyclohexane-1,2-diamine
      (chxdedpam) spacers were investigated as potential contrast agents in magnetic
      resonance imaging (MRI). The properties of the complexes were compared to that of
      the analogues containing 6-methylpicolinate units (dedpa2- and chxdedpa2-). The X
      ray structure of the [Ni(dedpam)]2+ complex reveals a six-coordinated metal ion
      with a distorted octahedral environment. The protonation constants of the dedpa2-
      and dedpam ligands and the stability constants of their Ni2+ complexes were
      determined using pH-potentiometry and spectrophotometric titrations (25  degrees
      C, 0.15 M NaCl). The [Ni(dedpa)] complex (log KNiL = 20.88(1)) was found to be
      considerably more stable than the corresponding amide derivative [Ni(dedpam)]2+
      (log KNiL = 14.29(2)). However, the amide derivative [Ni(chxdedpam)]2+ was found
      to be considerably more inert with respect to proton-assisted dissociation than
      the carboxylate derivative [Ni(chxdedpa)]. A detailed 1H NMR and DFT study was
      conducted to assign the 1H NMR spectra of the [Ni(chxdedpa)] and
      [Ni(chxdedpam)]2+ complexes. The observed 1H NMR paramagnetic shifts were found
      to be dominated by the Fermi contact contribution. The amide resonances of
      [Ni(chxdedpam)]2+ at 91.5 and 22.2 ppm were found to provide a sizeable chemical
      exchange saturation transfer effect, paving the way for the development of NiCEST
      agents based on these rigid non-macrocyclic platforms.

PMID- 29067397
TI  - Visible detection of copper ions using a fluorescent probe based on red carbon
      dots and zirconium metal-organic frameworks.
AB  - A highly selective and sensitive ratiometric fluorescent probe for copper ions
      (Cu2+) in aqueous solution based on a blue zirconium metal-organic framework [UiO
      66-(COOH)2] with red bandgap fluorescent carbon quantum dots (R-BF-CQDs) is
      developed. UiO-66-(COOH)2 displays broad ligand-centered (LC) emission and R-BF
      CQDs shows red emission. Interestingly, the remaining -NH2 at the surface of the
      prepared R-BF-CQDs can coordinate Cu2+ efficiently and produce a strong visible
      absorption, which overlaps the emission of UiO-66-(COOH)2. There is also a strong
      coordination capacity of the Cu2+ ions with R-BF-CQDs and UiO-66-(COOH)2, which
      allows the energy donor and the energy receptor to be closer together. Both of
      these two conditions provide the possibility of spectral energy transfer. In
      practice, the LC emission of UiO-66-(COOH)2 becomes weaker with increasing
      concentration of Cu2+, whereas the red fluorescence of R-BF-CQDs increases
      slightly.

PMID- 29067398
TI  - Investigating gas sorption in an rht-metal-organic framework with 1,2,3-triazole
      groups.
AB  - Simulations of CO2 and H2 sorption were performed in an rht-metal-organic
      framework (MOF) that consists of Cu2+ ions coordinated to 5,5',5''-(4,4',4''
      (benzene-1,3,5-triyl)tris(1H-1,2,3-triazole-4,1-diyl))triisophthalate (BTTI)
      linkers; it is referred to as Cu-BTTI herein. This MOF was previously synthesized
      and reported by three different experimental groups [Zhao et al., Sci. Rep.,
      2013, 3, 1149; Schroder et al., Chem. Sci., 2013, 4, 1731-1736; Hupp et al.,
      Energy Environ. Sci., 2013, 6, 1158-1163]. This MOF is notable for the presence
      of open-metal sites and nitrogen-rich regions through the copper paddlewheel
      ([Cu2(O2CR)4]) clusters and 1,2,3-triazole groups, respectively, which allows
      this material to display remarkable CO2 and H2 sorption properties. All three
      groups report distinct experimental and theoretical gas sorption results for the
      MOF. In contrast to the force fields utilized in the aforementioned studies, our
      simulations include explicit many-body polarization interactions, which was
      important to reproduce sorption onto the open-metal sites. Simulations using
      polarizable potentials for the MOF and sorbates generated sorption isotherms and
      isosteric heat of adsorption (Qst) values that are outstanding agreement with the
      corresponding experimental data for all three groups; this is in contrast to the
      theoretical results presented in the respective original references. The
      simulations carried out in the previous studies often looked reasonable but they
      missed a key feature of the sorption process that lead to unreliable results.
      Analysis of the radial distribution function (g(r)) about the open-metal sites
      and examination of the modeled structure reveal that the CO2 and H2 molecules
      prefer to sorb onto two unique types of Cu2+ ions that exhibit the highest
      partial positive charges. Sorption was also observed within the corners of the
      truncated tetrahedral (T-Td) cages and onto the 1,2,3-triazole groups of the
      linkers for both sorbates. Overall, this study demonstrates how utilizing a
      classical polarizable force field led to the reproduction of experimental
      observables and allowed for an accurate description of the sorption mechanism in
      this MOF that is an important member of the rht-MOF family.

PMID- 29067399
TI  - Determination of pore-scale hydrate phase equilibria in sediments using lab-on-a
      chip technology.
AB  - We present an experimental protocol for fast determination of hydrate stability
      in porous media for a range of pressure and temperature (P, T) conditions. Using
      a lab-on-a-chip approach, we gain direct optical access to dynamic pore-scale
      hydrate formation and dissociation events to study the hydrate phase equilibria
      in sediments. Optical pore-scale observations of phase behavior reproduce the
      theoretical hydrate stability line with methane gas and distilled water, and
      demonstrate the accuracy of the new method. The procedure is applicable for any
      kind of hydrate transitions in sediments, and may be used to map gas hydrate
      stability zones in nature.

PMID- 29067400
TI  - Tongue- and Jaw-Specific Contributions to Acoustic Vowel Contrast Changes in the
      Diphthong /ai/ in Response to Slow, Loud, and Clear Speech.
AB  - Purpose: This study sought to determine decoupled tongue and jaw displacement
      changes and their specific contributions to acoustic vowel contrast changes
      during slow, loud, and clear speech. Method: Twenty typical talkers repeated "see
      a kite again" 5 times in 4 speech conditions (typical, slow, loud, clear). Speech
      kinematics were recorded using 3-dimensional electromagnetic articulography.
      Tongue composite displacement, decoupled tongue displacement, and jaw
      displacement during /ai/, as well as the distance between /a/ and /i/ in the F1
      F2 vowel space, were examined during the diphthong /ai/ in "kite." Results:
      Displacements significantly increased during all 3 speech modifications. However,
      jaw displacements increased significantly more during clear speech than during
      loud and slow speech, whereas decoupled tongue displacements increased
      significantly more during slow speech than during clear and loud speech. In
      addition, decoupled tongue displacements increased significantly more during
      clear speech than during loud speech. Increases in acoustic vowel contrast tended
      to be larger during slow speech than during clear speech and were predominantly
      tongue-driven, whereas those during clear speech were fairly equally accounted
      for by changes in decoupled tongue and jaw displacements. Increases in acoustic
      vowel contrast during loud speech were smallest and were predominantly tongue
      driven, particularly in men. Conclusions: Findings suggest that task-specific
      patterns of decoupled tongue and jaw displacement change and task-specific
      patterns of decoupled tongue and jaw contributions to vowel acoustic change
      across these speech modifications. Clinical implications are discussed.

PMID- 29067401
TI  - Motion-generated optical information allows event perception despite blurry
      vision in AMD and amblyopic patients.
AB  - Events consist of objects in motion. When objects move, their opaque surfaces
      reflect light and produce both static image structure and dynamic optic flow. The
      static and dynamic optical information co-specify events. Patients with age
      related macular degeneration (AMD) and amblyopia cannot identify static objects
      because of weakened image structure. However, optic flow is detectable despite
      blurry vision because visual motion measurement uses low spatial frequencies.
      When motion ceases, image structure persists and might preserve properties
      specified by optic flow. We tested whether optic flow and image structure
      interact to allow event perception with poor static vision. AMD (Experiment 1),
      amblyopic (Experiments 2 and 3), and normally sighted observers identified common
      events from either blurry (Experiments 1 and 2) or clear images (Experiment 3),
      when either single image frames were presented, a sequence of frames was
      presented with motion masks, or a sequence of frames was presented with
      detectable motion. Results showed that with static images, but no motion, events
      were not perceived well by participants other than controls in Experiment 3.
      However, with detectable motion, events were perceived. Immediately following
      this and again after five days, participants were able to identify events from
      the original static images. So, when image structure information is weak, optic
      flow compensates for it and enables event perception. Furthermore, weakened
      static image structure information nevertheless preserves information that was
      once available in optic flow. The combination is powerful and allows events to be
      perceived accurately and stably despite blurry vision.

PMID- 29067403
TI  - Incorrect Dosage Information in Table.

PMID- 29067404
TI  - Robotic-Assisted Surgery: Balancing Evidence and Implementation.

PMID- 29067402
TI  - Optic Nerve Hypoplasia Is a Pervasive Subcortical Pathology of Visual System in
      Neonates.
AB  - Purpose: Optic nerve hypoplasia (ONH) is the most common cause of childhood
      congenital blindness in developed nations, yet the fundamental pathobiology of
      ONH remains unknown. The objective of this study was to employ a 'face validated'
      murine model to determine the timing of onset and the pathologic characteristics
      of ONH. Methods: Based on the robust linkage between X-linked CASK
      haploinsufficiency and clinically diagnosed ONH, we hypothesized that
      heterozygous deletion of CASK (CASK(+/-)) in rodents will produce an optic nerve
      pathology closely recapitulating ONH. We quantitatively analyzed the entire
      subcortical visual system in female CASK(+/-) mice using immunohistochemistry,
      anterograde axonal tracing, toluidine blue staining, transmission electron
      microscopy, and serial block-face scanning electron microscopy. Results: CASK
      haploinsuffiency in mice phenocopies human ONH with complete penetrance, thus
      satisfying the 'face validity'. We demonstrate that the optic nerve in CASK(+/-)
      mice is not only thin, but is comprised of atrophic retinal axons and displays
      reactive astrogliosis. Myelination of the optic nerve axons remains unchanged.
      Moreover, we demonstrate a significant decrease in retinal ganglion cell (RGC)
      numbers and perturbation in retinothalamic connectivity. Finally, we used this
      mouse model to define the onset and progression of ONH pathology, demonstrating
      for the first time that optic nerve defects arise at neonatally in CASK(+/-)mice.
      Conclusions: Optic nerve hypoplasia is a complex neuropathology of the
      subcortical visual system involving RGC loss, axonopathy, and synaptopathy and
      originates at a developmental stage in mice that corresponds to the late third
      trimester development in humans.

PMID- 29067405
TI  - Prehospital Blood Transfusion for Combat Casualties.

PMID- 29067406
TI  - Bayesian Analysis: Using Prior Information to Interpret the Results of Clinical
      Trials.

PMID- 29067408
TI  - Federal Task Force to Address Pain Management.

PMID- 29067407
TI  - NIH Funds "Tissue Chip" Models for Drug Screening.

PMID- 29067409
TI  - New Data on Suicide Risk Among Military Veterans.

PMID- 29067411
TI  - Long-term Care: Investing in Models That Work.

PMID- 29067412
TI  - Treatment of the Opium Neurosis: By Stephen Lett, M.D., Ont., Canada.

PMID- 29067413
TI  - Excretion of the Herbicide Glyphosate in Older Adults Between 1993 and 2016.

PMID- 29067414
TI  - Improving Direct-to-Consumer Medical Testing.

PMID- 29067415
TI  - Prediabetes Prevalence in China.

PMID- 29067416
TI  - PET Scans With 18F-Fluorodeoxyglucose to Diagnose Adrenal Tumors.

PMID- 29067417
TI  - Prediabetes Prevalence in China-Reply.

PMID- 29067418
TI  - Improving Direct-to-Consumer Medical Testing-Reply.

PMID- 29067419
TI  - PET Scans With 18F-Fluorodeoxyglucose to Diagnose Adrenal Tumors-Reply.

PMID- 29067420
TI  - Prasterone (Intrarosa) for Dyspareunia.

PMID- 29067422
TI  - Intervention Improves Adherence to Opioid Prescribing Guidelines.

PMID- 29067421
TI  - Liraglutide May Reduce Diabetic Kidney Disease.

PMID- 29067423
TI  - Baby-Led Weaning Does Not Reduce Risk of Overweight.

PMID- 29067424
TI  - Lay Workers Can Ease Distress in Women Exposed to Violence.

PMID- 29067425
TI  - PCPs Can Manage Genomic Results but Clinical Utility Is Limited.

PMID- 29067426
TI  - Effect of Robotic-Assisted vs Conventional Laparoscopic Surgery on Risk of
      Conversion to Open Laparotomy Among Patients Undergoing Resection for Rectal
      Cancer: The ROLARR Randomized Clinical Trial.
AB  - Importance: Robotic rectal cancer surgery is gaining popularity, but limited data
      are available regarding safety and efficacy. Objective: To compare robotic
      assisted vs conventional laparoscopic surgery for risk of conversion to open
      laparotomy among patients undergoing resection for rectal cancer. Design,
      Setting, and Participants: Randomized clinical trial comparing robotic-assisted
      vs conventional laparoscopic surgery among 471 patients with rectal
      adenocarcinoma suitable for curative resection conducted at 29 sites across 10
      countries, including 40 surgeons. Recruitment of patients was from January 7,
      2011, to September 30, 2014, follow-up was conducted at 30 days and 6 months, and
      final follow-up was on June 16, 2015. Interventions: Patients were randomized to
      robotic-assisted (n = 237) or conventional (n = 234) laparoscopic rectal cancer
      resection, performed by either high (upper rectum) or low (total rectum) anterior
      resection or abdominoperineal resection (rectum and perineum). Main Outcomes and
      Measures: The primary outcome was conversion to open laparotomy. Secondary end
      points included intraoperative and postoperative complications, circumferential
      resection margin positivity (CRM+) and other pathological outcomes, quality of
      life (36-Item Short Form Survey and 20-item Multidimensional Fatigue Inventory),
      bladder and sexual dysfunction (International Prostate Symptom Score,
      International Index of Erectile Function, and Female Sexual Function Index), and
      oncological outcomes. Results: Among 471 randomized patients (mean [SD] age, 64.9
      [11.0] years; 320 [67.9%] men), 466 (98.9%) completed the study. The overall rate
      of conversion to open laparotomy was 10.1%: 19 of 236 patients (8.1%) in the
      robotic-assisted laparoscopic group and 28 of 230 patients (12.2%) in the
      conventional laparoscopic group (unadjusted risk difference = 4.1% [95% CI, -1.4%
      to 9.6%]; adjusted odds ratio = 0.61 [95% CI, 0.31 to 1.21]; P = .16). The
      overall CRM+ rate was 5.7%; CRM+ occurred in 14 (6.3%) of 224 patients in the
      conventional laparoscopic group and 12 (5.1%) of 235 patients in the robotic
      assisted laparoscopic group (unadjusted risk difference = 1.1% [95% CI, -3.1% to
      5.4%]; adjusted odds ratio = 0.78 [95% CI, 0.35 to 1.76]; P = .56). Of the other
      8 reported prespecified secondary end points, including intraoperative
      complications, postoperative complications, plane of surgery, 30-day mortality,
      bladder dysfunction, and sexual dysfunction, none showed a statistically
      significant difference between groups. Conclusions and Relevance: Among patients
      with rectal adenocarcinoma suitable for curative resection, robotic-assisted
      laparoscopic surgery, as compared with conventional laparoscopic surgery, did not
      significantly reduce the risk of conversion to open laparotomy. These findings
      suggest that robotic-assisted laparoscopic surgery, when performed by surgeons
      with varying experience with robotic surgery, does not confer an advantage in
      rectal cancer resection. Trial Registration: isrctn.org Identifier:
      ISRCTN80500123.

PMID- 29067427
TI  - Association of Robotic-Assisted vs Laparoscopic Radical Nephrectomy With
      Perioperative Outcomes and Health Care Costs, 2003 to 2015.
AB  - Importance: Use of robotic surgery has increased in urological practice over the
      last decade. However, the use, outcomes, and costs of robotic nephrectomy are
      unknown. Objectives: To examine the trend in use of robotic-assisted operations
      for radical nephrectomy in the United States and to compare the perioperative
      outcomes and costs with laparoscopic radical nephrectomy. Design, Setting, and
      Participants: This retrospective cohort study used the Premier Healthcare
      database to evaluate outcomes of patients who had undergone robotic-assisted or
      laparoscopic radical nephrectomy for renal mass at 416 US hospitals between
      January 2003 and September 2015. Multivariable regression modeling was used to
      assess outcomes. Exposures: Robotic-assisted vs laparoscopic radical nephrectomy.
      Main Outcomes and Measures: The primary outcome of the study was the trend in use
      of robotic-assisted radical nephrectomy. The secondary outcomes were
      perioperative complications, based on the Clavien classification system, and
      defined as any complication (Clavien grades 1-5) or major complications (Clavien
      grades 3-5, for which grade 5 results in death); resource use (operating time,
      blood transfusion, length of hospital stay); and direct hospital cost. Results:
      Among 23 753 patients included in the study (mean age, 61.4 years; men, 13 792
      [58.1%]), 18 573 underwent laparoscopic radical nephrectomy and 5180 underwent
      robotic-assisted radical nephrectomy. Use of robotic-assisted surgery increased
      from 1.5% (39 of 2676 radical nephrectomy procedures in 2003) to 27.0% (862 of
      3194 radical nephrectomy procedures) in 2015 (P for trend <.001). In the weighted
      adjusted analysis, there were no significant differences between robotic-assisted
      and laparoscopic radical nephrectomy in the incidence of any (Clavien grades 1-5)
      postoperative complications (adjusted rates, 22.2% vs 23.4%, difference, -1.2%;
      95% CI, -5.4 to 3.0%) or major (Clavien grades 3-5) complications (adjusted
      rates, 3.5% vs 3.8%, difference, -0.3%; 95% CI, -1.0% to 0.5%). The rate of
      prolonged operating time (>4 hours) for patients undergoing the robotic-assisted
      procedure was higher than for patients receiving the laparoscopic procedure in
      the adjusted analysis (46.3% vs 25.8%; risk difference, 20.5%; 95% CI, 14.2% to
      26.8%). Robotic-assisted radical nephrectomy was associated with higher mean 90
      day direct hospital costs ($19 530 vs $16 851; difference, $2678; 95% CI, $838 to
      $4519), mainly accounted for operating room ($7217 vs $5378; difference, $1839;
      95% CI, $1050 to $2628) and supply costs ($4876 vs $3891; difference, $985; 95%
      CI, $473 to $1498). Conclusions and Relevance: Among patients undergoing radical
      nephrectomy for renal mass between 2003 and 2015, the use of robotic-assisted
      surgery increased substantially. The use of robotic-assistance was not associated
      with increased risk of any or major complications but was associated with
      prolonged operating time and higher hospital costs compared with laparoscopic
      surgery.

PMID- 29067430
TI  - Urinary Incontinence in Women.

PMID- 29067431
TI  - Lear as an Aging Musician.

PMID- 29067429
TI  - Association of Prehospital Blood Product Transfusion During Medical Evacuation of
      Combat Casualties in Afghanistan With Acute and 30-Day Survival.
AB  - Importance: Prehospital blood product transfusion in trauma care remains
      controversial due to poor-quality evidence and cost. Sequential expansion of
      blood transfusion capability after 2012 to deployed military medical evacuation
      (MEDEVAC) units enabled a concurrent cohort study to focus on the timing as well
      as the location of the initial transfusion. Objective: To examine the association
      of prehospital transfusion and time to initial transfusion with injury survival.
      Design, Setting, and Participants: Retrospective cohort study of US military
      combat casualties in Afghanistan between April 1, 2012, and August 7, 2015.
      Eligible patients were rescued alive by MEDEVAC from point of injury with either
      (1) a traumatic limb amputation at or above the knee or elbow or (2) shock
      defined as a systolic blood pressure of less than 90 mm Hg or a heart rate
      greater than 120 beats per minute. Exposures: Initiation of prehospital
      transfusion and time from MEDEVAC rescue to first transfusion, regardless of
      location (ie, prior to or during hospitalization). Transfusion recipients were
      compared with nonrecipients (unexposed) for whom transfusion was delayed or not
      given. Main Outcomes and Measures: Mortality at 24 hours and 30 days after
      MEDEVAC rescue were coprimary outcomes. To balance injury severity, nonrecipients
      of prehospital transfusion were frequency matched to recipients by mechanism of
      injury, prehospital shock, severity of limb amputation, head injury, and torso
      hemorrhage. Cox regression was stratified by matched groups and also adjusted for
      age, injury year, transport team, tourniquet use, and time to MEDEVAC rescue.
      Results: Of 502 patients (median age, 25 years [interquartile range, 22 to 29
      years]; 98% male), 3 of 55 prehospital transfusion recipients (5%) and 85 of 447
      nonrecipients (19%) died within 24 hours of MEDEVAC rescue (between-group
      difference, -14% [95% CI, -21% to -6%]; P = .01). By day 30, 6 recipients (11%)
      and 102 nonrecipients (23%) died (between-group difference, -12% [95% CI, -21% to
      -2%]; P = .04). For the 386 patients without missing covariate data among the 400
      patients within the matched groups, the adjusted hazard ratio for mortality
      associated with prehospital transfusion was 0.26 (95% CI, 0.08 to 0.84, P = .02)
      over 24 hours (3 deaths among 54 recipients vs 67 deaths among 332 matched
      nonrecipients) and 0.39 (95% CI, 0.16 to 0.92, P = .03) over 30 days (6 vs 76
      deaths, respectively). Time to initial transfusion, regardless of location
      (prehospital or during hospitalization), was associated with reduced 24-hour
      mortality only up to 15 minutes after MEDEVAC rescue (median, 36 minutes after
      injury; adjusted hazard ratio, 0.17 [95% CI, 0.04 to 0.73], P = .02; there were 2
      deaths among 62 recipients vs 68 deaths among 324 delayed transfusion recipients
      or nonrecipients). Conclusions and Relevance: Among medically evacuated US
      military combat causalities in Afghanistan, blood product transfusion prehospital
      or within minutes of injury was associated with greater 24-hour and 30-day
      survival than delayed transfusion or no transfusion. The findings support
      prehospital transfusion in this setting.

PMID- 29067432
TI  - A Death in the Family.

PMID- 29067428
TI  - Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or
      Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized
      Clinical Trial.
AB  - Importance: Hypothermia initiated at less than 6 hours after birth reduces death
      or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or
      later gestation. To our knowledge, hypothermia trials have not been performed in
      infants presenting after 6 hours. Objective: To estimate the probability that
      hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or
      disability at 18 months among infants with hypoxic-ischemic encephalopathy.
      Design, Setting, and Participants: A randomized clinical trial was conducted
      between April 2008 and June 2016 among infants at 36 weeks' or later gestation
      with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours
      after birth. Twenty-one US Neonatal Research Network centers participated.
      Bayesian analyses were prespecified given the anticipated limited sample size.
      Interventions: Targeted esophageal temperature was used in 168 infants. Eighty
      three hypothermic infants were maintained at 33.5 degrees C (acceptable range, 33
      degrees C-34 degrees C) for 96 hours and then rewarmed. Eighty-five noncooled
      infants were maintained at 37.0 degrees C (acceptable range, 36.5 degrees C-37.3
      degrees C). Main Outcomes and Measures: The composite of death or disability
      (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and
      age at randomization. Results: Hypothermic and noncooled infants were term (mean
      [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and
      55 of 85 (65%) were male, respectively. Both groups were acidemic at birth,
      predominantly transferred to the treating center with moderate encephalopathy,
      and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and
      noncooled groups, respectively. The primary outcome occurred in 19 of 78
      hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute
      difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior
      indicated a 76% posterior probability of reduced death or disability with
      hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86;
      95% credible interval, 0.58-1.29). The probability that death or disability in
      cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%,
      64%, and 56%, respectively. Conclusions and Relevance: Among term infants with
      hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after
      birth compared with noncooling resulted in a 76% probability of any reduction in
      death or disability, and a 64% probability of at least 2% less death or
      disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth
      may have benefit but there is uncertainty in its effectiveness. Trial
      Registration: clinicaltrials.gov Identifier: NCT00614744.

PMID- 29067433
TI  - Urinary Incontinence in Women: A Review.
AB  - Importance: Urinary incontinence, the involuntary loss of urine, is a common
      health condition that may decrease quality of life. Ten to twenty percent of
      women and up to 77% of women residing in nursing homes have urinary incontinence,
      yet only 25% seek or receive treatment. Observations: This review summarizes the
      evaluation and therapeutic options for women affected by urinary incontinence.
      The initial assessment should focus on understanding the effect of incontinence
      on quality of life, the patient's goals and preferences for treatment, the
      results of previous treatments, and the presence of concomitant conditions, such
      as advanced pelvic organ prolapse, that may require referral. Infection and
      hematuria need to be ruled out. In the absence of urinary infection or serious
      underlying pathology (such as cancer or serious neurologic disease) associated
      with urinary incontinence, the clinician should initiate unsupervised pelvic
      muscle exercises and lifestyle modifications appropriate to the patient to reduce
      her symptoms. These recommendations can include weight loss, adequate hydration,
      avoidance of excessive fluids, and regular voiding intervals that reduce urgency
      incontinence episodes. Urgency incontinence medications, with timely reassessment
      of symptoms, can be started without extensive evaluation. Specialist treatments
      for urgency incontinence include onabotulinumtoxinA and percutaneous or implanted
      neuromodulators. Stress incontinence surgery, the midurethral sling, is
      associated with symptom improvement in 48% to 90% of women and has low rates of
      mesh complications (<5%). Conclusions and Relevance: Urinary incontinence is
      common in women, although few seek care despite many effective treatment options.
      Clinicians should prioritize urinary incontinence detection, identify and treat
      modifiable factors, incorporate patient preference into evaluation and treatment,
      initiate conservative and medical therapy, and refer to specialists when
      underlying pathology is identified or conservative measures are ineffective.

PMID- 29067435
TI  - Hispanic Kids Shoulder High Leukemia Burden.

PMID- 29067436
TI  - Brucella in Raw Milk Prompts Health Warning in Texas.

PMID- 29067437
TI  - Maresin 1 inhibits transforming growth factor-beta1-induced proliferation,
      migration and differentiation in human lung fibroblasts.
AB  - The myofibroblast has been implicated to be an important pathogenic cell in all
      fibrotic diseases, through synthesis of excess extracellular matrix. Lung
      fibroblast migration, proliferation and differentiation into a myofibroblast-like
      cell type are regarded as important steps in the formation of lung fibrosis. In
      the present study, the effect of maresin 1 (MaR 1), a pro-resolving lipid
      mediator, on transforming growth factor (TGF)-beta1-stimulated lung fibroblasts
      was investigated, and the underlying molecular mechanisms were examined. The
      results of the present study demonstrated that MaR 1 inhibited TGF-beta1-induced
      proliferative and migratory ability, assessed using MTT and scratch wound healing
      assays. The TGF-beta1-induced expression of alpha-smooth muscle actin (alpha-SMA)
      and collagen type I, the hallmarks of myofibroblast differentiation, was
      decreased by MaR 1 at the mRNA and protein levels, determined using the reverse
      transcription-quantitative polymerase chain reaction and western blot analysis,
      respectively. Immunofluorescence demonstrated that MaR 1 downregulated the TGF
      beta1-induced expression of alpha-SMA. In addition, phosphorylated mothers
      against decapentaplegic homolog 2/3 (Smad2/3) and extracellular signal-related
      kinases (ERK) 1/2 were upregulated in TGF-beta1-induced lung fibroblasts, and
      these effects were attenuated by MaR 1 administration. In conclusion, the results
      of the present study demonstrated that MaR 1 inhibited the TGF-beta1-induced
      proliferation, migration and differentiation of human lung fibroblasts. These
      observed effects may be mediated in part by decreased phosphorylation of Smad2/3
      and ERK1/2 signaling pathways. Therefore, MaR 1 may be a potential therapeutic
      approach to lung fibrotic diseases.

PMID- 29067438
TI  - miRNA-140 inhibits C3H10T1/2 mesenchymal stem cell proliferation by targeting
      CXCL12 during transforming growth factor-beta3-induced chondrogenic
      differentiation.
AB  - The aim of the present study was to investigate the role of microRNA (miRNA or
      miR)-140 in C3H10T1/2 mesenchymal stem cells (MSCs). Cluster analysis was used to
      evaluate the miRNA expression profile. The expression level of miRNA-140 was
      validated by reverse transcription-quantitative polymerase chain reaction (RT
      qPCR). TargetScan and microRNA.org databases were used to predict target miRNAs
      and cartilage-associated target genes. Binding sites between miR-140 and the
      target gene were predicted by bioinformatics software. A dual-luciferase reporter
      assay was performed to determine whether miR-140 could target C-X-C motif
      chemokine ligand 12 (CXCL12). Following the promotion/inhibition of miR-140, 1, 7
      and 14 days following transforming growth factor-beta3 (TGF-beta3)-induction,
      western blotting was utilized to evaluate CXCL12 protein levels. MTT assays and
      alcian blue staining were applied to assess C3H10T1/2 MSC viability and
      chondrogenic differentiation, respectively. In the TGF-beta3-induced group, RT
      qPCR verified that the mRNA level of Mus musculus (mmu)-miR-140 was significantly
      elevated when compared with the control group. miR-140 was predicted to recognize
      and interact with CXCL12-3'UTR and the dual luciferase reporter assay further
      validated that miR-140 targeted the predicted region of CXCL12. CXCL12 was
      markedly decreased following miR-140 overexpression and visibly increased
      following miR-140 inhibition. In addition, the level of CXCL12 expression
      declined as the duration of induction increased. Following the
      promotion/inhibition of miR-140, at 1 and 7 days following TGF-beta3-induction,
      C3H10T1/2 MSCs inhibited or promoted cell viability, respectively, when compared
      with the control groups. In addition, in pellets achieved by chondrogenic
      differentiation following the induction of C3H10T1/2 MSCs for 7 days, alcian blue
      staining revealed no significant difference in characteristic extracellular
      matrix glycosaminoglycans between the miR-140 up and downregulated groups, and
      their respective control groups. The present study concludes that miRNA-140
      inhibition promoted C3H10T1/2 MSC viability however, not C3H10T1/2 MSC
      differentiation by targeting and reducing CXCL12 protein levels during the
      process of TGF-beta3-induced chondrogenic differentiation. In conclusion, the
      present study provided a potential target for the treatment of cartilage
      defection.

PMID- 29067440
TI  - CD-PLLD co-delivering docetaxel and MMP-9 siRNA plasmid for nasopharyngeal
      carcinoma therapy in vivo.
AB  - The co-delivery of a drug and a target gene has become a primary strategy in
      cancer therapy. Based on our previous study, a synthesized star-shaped co-polymer
      consisting of beta-cyclodextrin (CD) and a poly(L-lysine) dendron (PLLD) was used
      to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP-9) small
      interfering RNA, via CD-PLLD/DOC/MMP-9 complexes, into mice implanted with HNE-1
      human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly
      used amphiphilic co-polymer micelles, the obtained CD derivative may be used
      directly for a combined delivery of nucleic acid and hydrophobic DOC without a
      complicated micellization process. In vivo assays demonstrated that CD
      PLLD/DOC/MMP-9 inhibited HNE-1 tumor growth and decreased proliferating cell
      nuclear antigen expression levels, indicating a potential strategy for NPC
      therapy. In addition, the distribution of DOC and MMP-9 was investigated; CD
      PLLD/DOC/MMP-9 complexes were phagocytized in reticuloendothelial systems,
      including the liver and spleen, which requires further study. Furthermore, the
      complexes did not cross the blood-brain barrier due to their large molecular
      size, suggesting they may be relatively safe. Additionally, the complexes
      mediated increased DOC concentrations with prolonged blood circulation and EGFP
      expression in HNE-1 tumors. These results suggest the future potential
      application of CD-PLLD/DOC/MMP-9 for NPC therapy.

PMID- 29067439
TI  - Apolipoprotein M increases the expression of vitamin D receptor mRNA in
      colorectal cancer cells detected with duplex fluorescence reverse transcription
      quantitative polymerase chain reaction.
AB  - Apolipoprotein M (ApoM) and the vitamin D receptor (VDR) are apolipoproteins
      predominantly presenting in high-density lipoprotein (HDL) and a karyophilic
      protein belonging to the steroid-thyroid receptor superfamily, respectively.
      Previous studies have demonstrated that ApoM and VDR are associated with
      cholesterol metabolism, immune and colorectal cancer regulation. In order to
      investigate whether ApoM affected the expression of VDR in colorectal cancer
      cells, a single-tube duplex fluorescence reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) system was developed to simultaneously detect
      the mRNA levels of VDR and GAPDH in HT-29 cells overexpressing ApoM. The results
      demonstrated that the amplification products were confirmed as the specific
      fragment of VDR/GAPDH using the DNA sequencing instrument. The sensitivity,
      linear range, correlation coefficient, amplification efficiency, intra-assay and
      inter-assay coefficients of variation were 40 copies/ul, 4.00x101-4.00x105
      copies/ul, 0.999, 92.42%, 0.09-0.34% and 0.32-0.65% for VDR, and 40 copies/ul,
      4.00x101-4.00x105 copies/ul, 0.999, 98.07%, 0.19-0.43% and 0.40-0.75% for GAPDH,
      respectively. The results indicated that the expression of VDR mRNA was
      significantly higher in HT-29 cells overexpressing ApoM, compared with the
      negative control group (P<0.05). In conclusion, the current study successfully
      developed the single-tube duplex RT-qPCR to simultaneously detect VDR and GAPDH
      expression in colorectal cancer cells. The methodology results demonstrated that
      the duplex RT-qPCR system with high sensitivity and specificity could ensure the
      objectivity and credibility of the detection. The present study confirmed that
      ApoM significantly increased the expression of VDR in HT-29 cells. In addition,
      it was hypothesized that ApoM may be involved in antineoplastic activity via the
      upregulation of VDR expression, which may provide novel directions for the
      investigation of ApoM in cancer.

PMID- 29067441
TI  - Multiplex picoliter-droplet digital PCR for quantitative assessment of EGFR
      mutations in circulating cell-free DNA derived from advanced non-small cell lung
      cancer patients.
AB  - To explore the possible diagnostic value of liquid biopsy, two multiplex panels
      using picoliter-droplet digital polymerase chain reaction (ddPCR) were
      established to quantitatively assess the epidermal growth factor receptor (EGFR)
      mutations in cell-free DNA (cfDNA) extracted from the plasma of advanced non
      small cell lung cancer (NSCLC) patients. Plasma samples derived from 22 patients
      with stage IIIB/IV NSCLC harboring EGFR mutations in matched tumor tissues
      confirmed by amplification refractory mutation system (ARMS) analysis were
      subjected to two multiplex ddPCR panels to assess the abundance of tyrosine
      kinase inhibitor (TKI) -sensitive (19DEL, L858R) and TKI-resistant (T790 M)
      mutations. Fluctuations in EGFR mutant abundance were monitored by either of the
      multiplex ddPCR panels for three patients undergoing EGFR-TKI treatment, with
      serial plasma sample collections over 2 months. The multiplex ddPCR panels
      applied to plasma cfDNA from advanced NSCLC patients achieved a total concordance
      rate of 80% with the EGFR mutation profiles obtained by ARMS from matched biopsy
      tumor specimens (90% for 19DEL, 95% for L858R, 95% for T790M, respectively) and
      revealed additional mutant alleles in two subjects. The respective sensitivity
      and specificity were 90.9 and 88.9% for 19DEL, 87.5 and 100% for L858R, 100 and
      93.8% for T790M. The fluctuations of EGFR mutant abundance in serial plasma cfDNA
      were in accordance with the changes in tumor size as assessed by imaging scans.
      The authors demonstrated the utility of multiplex ddPCR panels with ultra
      sensitivity for quantitative analysis of EGFR mutations in plasma cfDNA and
      obtained promising usefulness in EGFR-TKI decision-making for advanced NSCLC
      patients.

PMID- 29067442
TI  - Wnt/beta-catenin signaling pathway in trophoblasts and abnormal activation in
      preeclampsia (Review).
AB  - Preeclampsia (PE) is one of the most common types of hypertensive disease and
      occurs in 3-4% of pregnancies. There are a number of theories on the pathogenesis
      of PE. Abnormal differentiation of the placenta may lead to failure of
      trophoblast migration, shallow placenta implantation and placental
      ischemia/hypoxia, followed by the subsequent occurrence of PE. The Wnt/beta
      catenin pathway is a canonical Wnt-signaling pathway that regulates several
      biological processes, including proliferation, migration, invasion and apoptosis.
      Abnormal activation of the Wnt/beta-catenin signaling pathway may serve an
      important role in the pathogenesis of various human diseases, particularly in
      human cancer. Recent studies have demonstrated that the dysregulation of the
      Wnt/beta-catenin signaling pathway may contribute to PE. The present review aims
      to summarize the articles on Wnt/beta-catenin signaling pathway in the
      trophoblast and abnormal activation in PE. Wnt/beta-catenin signaling may serve a
      significant role in the pathogenesis of PE and may be a prospective therapeutic
      target for the prevention and treatment of PE.

PMID- 29067443
TI  - Role of ADAMTS13 in diet-induced liver steatosis.
AB  - Previous studies, predominantly based on increased or decreased plasma levels,
      have reported conflicting data on a potential functional role of ADAMTS13 in the
      pathogenesis of liver diseases, including non-alcoholic steatohepatitis (NASH).
      The aim of the current study was to evaluate whether ADAMTS13 deficiency affects
      development of NASH. Therefore, male wild-type (WT) and Adamts13 deficient
      (Adamts13-/-) mice were kept on a steatosis-inducing diet devoid of methionine
      and choline (MCD) or a control diet (MCC) for 4 weeks. Induction of NASH did not
      affect plasma ADAMTS13 antigen levels of WT mice. MCD as compared with MCC
      feeding resulted in reduced body and liver weight with no differences between the
      genotypes. Plasma levels of the liver enzymes AST and ALT were significantly
      higher for MCD vs. MCC fed Adamts13-/- and WT mice, however were not different
      between the genotypes. Liver triglyceride levels were also higher after MCD
      feeding, but were not different between WT and Adamts13-/- mice. Adamts13-/- mice
      on the two diets exhibited higher insulin sensitivity when compared with WT mice.
      On the MCC diet, the genotype did not show clear histological abnormalities in
      the liver, whereas severe steatosis and fibrosis were observed on MCD diet,
      however were comparable for both genotypes. This was supported by comparably
      enhanced hepatic expression in the two genotypes on MCD diet of the steatosis
      marker CD36 and of the fibrosis marker tissue inhibitor of metalloproteinase 1.
      Thus, the results of the current study do not support a functional role of
      ADAMTS13 in this murine model of NASH.

PMID- 29067444
TI  - Anti-inflammatory effects on murine macrophages of ethanol extracts of Lygodium
      japonicum spores via inhibition of NF-kappaB and p38.
AB  - The spores of Lygodium japonicum (Thunb.) Sw. (L. japonicum) have been used in
      traditional Chinese medicine for the treatment of various inflammatory diseases.
      However, the molecular mechanisms underlying their anti-inflammatory effects have
      yet to be elucidated. In the present study, we investigated the anti-inflammatory
      effects of ethanol extracts of L. japonicum spores (ELJ) by measuring the
      production of inflammatory mediators, and explored the molecular mechanisms
      underlying the effects of ELJ in murine macrophages in vitro using immunoblotting
      analyses. At non-cytotoxic concentrations of (50-300 ug/ml), ELJ was revealed to
      significantly suppress the production of nitric oxide (NO) and tumor necrosis
      factor (TNF)-alpha in lipopolysaccharide (LPS)-stimulated murine RAW 264.7
      macrophages; ELJ repressed the production of interleukin (IL)-6 only at high
      concentrations (>=200 ug/ml). The ELJ-mediated decrease in NO production was
      demonstrated to depend on the downregulation of inducible NO synthase mRNA and
      protein expression. Conversely, the mRNA and protein expression of cyclooxygenase
      2 were not affected by ELJ. In addition, ELJ was revealed to inhibit the mRNA
      expression of IL-6, IL-1beta, and TNF-alpha in LPS-stimulated RAW 264.7
      macrophages. The effects of ELJ on proinflammatory mediators may have been due to
      the stabilization of inhibitor of kappaBalpha and the inhibition of p38 mitogen
      activated protein kinase (MAPK). These results suggested that ELJ may suppress
      LPS-induced inflammatory responses in murine macrophages in vitro, through the
      negative regulation of p38 MAPK and nuclear factor (NF)-kappaB. Therefore, ELJ
      may have potential as a novel candidate for the development of therapeutic
      strategies aimed at alleviating inflammation.

PMID- 29067445
TI  - Bcl-2 associated athanogene 4 promotes proliferation, migration and invasion of
      gastric cancer cells.
AB  - Currently, with the increase of morbidity and mortality rate, gastric cancer (GC)
      is attracting increasing attention in China. Bcl-2-associated athanogene 4 (BAG4)
      has been identified as a tumor promoter in several tumors, but its role in GC
      remains unknown. The present study aimed to detect the expression of BAG4 and
      determine its function in the progression of GC. The results from reverse
      transcription-quantitative polymerase chain reaction and western blotting
      revealed that BAG4 was markedly upregulated in highly metastatic cell lines
      (SGC7901 and MGC803), compared with the lower-metastatic cell lines (AGS and
      BGC823). Through Cell Counting Kit-8, cell cycle, apoptosis, Transwell and colony
      formation assays, BAG4 was demonstrated to promote the proliferation, migration
      and invasion of GC cells in vitro. Additionally, in vivo assays further certified
      that BAG4 can increase the proliferation and invasion of GC cells. In conclusion,
      these findings implicate BAG4 as a potential therapeutic target for GC.

PMID- 29067446
TI  - Microarray expression profile analysis of long non-coding RNAs in optineurin E50K
      mutant transgenic mice.
AB  - The biological role of long non-coding RNAs (lncRNAs) involves various cellular
      processes and leads to human diseases. Mutations in the optineurin (OPTN) gene,
      including E50K, which encodes an amino acid substitution, have been associated
      with primary open angle glaucoma (POAG). The present study was designed to
      identify lncRNAs associated with OPTN (E50K) transgenic mice and investigate its
      functions in the pathogenesis of POAG. The retinas from six OPTN (E50K)
      transgenic and wild-type mice were collected separately, and lncRNA expression
      profiling was performed using microarray analysis. Based on Pearson's correlation
      analysis, an lncRNA and mRNA co-expression network was constructed. Gene Ontology
      (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the
      lncRNAs and coexpressed mRNAs was used to identify the associated biological
      modules and pathological pathways. The GO biological processes (BPs) of the
      differentially expressed lncRNAs were predicted using a computational method of
      gene set enrichment analysis. A total of 69 lncRNAs showed differential
      expression between the OPTN (E50K) transgenic mice and wild-type mice, which
      included 37 downregulated and 32 upregulated lncRNAs. The pathway analysis
      revealed that the lncRNAs coexpressed with mRNAs were enriched in mRNA
      surveillance and RNA transport pathways. In addition, eight lncRNAs were
      annotated in the GO BPs, and two of these eight lncRNAs, ASMM10P055228 and
      ASMM10P040128, were annotated with the negative regulation of oxidative stress
      induced cell death and regulation of execution phase of apoptosis. These results
      showed that lncRNAs were differentially expressed in the retinas between OPTN
      (E50K) transgenic and wild-type mice, and this may be important in the
      pathogenesis of POAG caused by the OPTN (E50K) mutation.

PMID- 29067447
TI  - RAGE antagonism by FPS-ZM1 attenuates postoperative cognitive dysfunction through
      inhibition of neuroinflammation in mice.
AB  - Neuroinflammation triggered by surgical trauma contributes to postoperative
      cognitive dysfunction (POCD). The receptor for advanced glycation end-products
      (RAGE), a multiligand inflammatory receptor, is involved in the damaging effects
      of various cellular processes, contributing to neuroinflammation and
      neurodegeneration. However, the potential role of RAGE in the acute period of
      POCD has not been fully investigated. C57BL/6 male mice undergoing surgery of the
      tibia under isoflurane anesthesia were treated with the RAGE antagonist FPS-ZM1
      or vehicle control intraperitoneally for a period of 7 days. The cognitive
      function of the animals was tested using trace fear conditioning on the third
      postoperative day. To determine astrocytic activation, microgliosis, p65
      expression, inflammatory factor levels and postsynaptic density protein-95 (PSD
      95) expression in the hippocampus, the animals were euthanized on either the
      first, third or seventh postoperative day. Compared with the control group, the
      cognitive function of the surgical animals was impaired on the third
      postoperative day. Astrocytic activation, microgliosis and the expression levels
      of p65, interleukin (IL)-1beta, IL-6, and PSD-95 were significantly increased on
      the first, and third postoperative days. However, tumor necrosis factor-alpha
      expression was significantly increased only on postoperative day 1. All of the
      surgical effects observed were partially inhibited by treatment with FPS-ZM1. In
      summary, the results of the present study suggest that RAGE serves an important
      role in the acute inflammatory process of POCD, and blocking RAGE can inhibit
      neuroinflammation and attenuate POCD. Thus, the RAGE signaling pathway may be a
      novel target in the prevention, and treatment of POCD.

PMID- 29067448
TI  - Downregulation of microRNA-448 improves isoflurane-induced learning and memory
      impairment in rats.
AB  - The present study aimed to investigate the potential role of microRNA-448 (miR
      448) in isoflurane-induced learning and memory impairment in rats. Sprague-Dawley
      rats were used for the construction of isoflurane-treated models. The Morris
      water maze test was used to evaluate the effects of isoflurane on rats regarding
      the following para-meters: Swimming speed, escape latency and time in original
      quadrant. Influences of isoflurane on neuron apoptosis and miR-448 expression in
      rat hippocampus tissue were analyzed by flow cytometry and reverse transcription
      quantitative polymerase chain reaction, respectively. Furthermore, the effects of
      miR-448 on the expression of cell apoptosis-associated proteins were investigated
      by flow cytometry. The results demonstrated that isoflurane treatment induced
      higher escape latency and lower time spent in original quadrant compared with the
      control rats. In addition, isoflurane treatment induced neuron apoptosis and miR
      448 was highly expressed in the hippocampal tissue of isoflurane-treated rats.
      Furthermore, Bcl-x was significantly downregulated while caspase-3 expression was
      upregulated by an miR-448 inhibitor. Combined the results of the current study
      indicate that miR-448 knockdown may have pivotal roles in improving isoflurane
      induced learning and memory impairment via suppressing neuron apoptosis.

PMID- 29067449
TI  - Diosgenin attenuates neuropathic pain in a rat model of chronic constriction
      injury.
AB  - Diosgenin is a steroidal saponin extract from numerous plants, including Solanum
      and Dioscorea species, and has been reported to possess neuroprotective activity.
      However, the role of diosgenin in neuropathic pain remains unclear. The present
      study examined the effects of diosgenin on allodynia and the levels of
      inflammatory mediators in rats following neuropathic pain evoked by chronic
      constriction injury (CCI). In addition, the underlying molecular mechanisms
      involved in diosgenin-induced suppression of neuropathic pain were examined. The
      results of the present study demonstrated diosgenin reversed CCI-decreased
      mechanical withdrawal threshold and thermal withdrawal latency. Furthermore,
      diosgenin inhibited CCI-induced upregulated levels of the pro-inflammatory
      cytokines tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-2, and
      suppressed oxidative stress induced by CCI in the spinal cord. Furthermore,
      diosgenin significantly inhibited the expression of phosphorylated-p38 mitogen
      activated protein kinase (MAPK) and nuclear factor (NF)-kappaB in the spinal cord
      in CCI rats compared with sham-operated rats. In conclusion, the present study
      demonstrated that diosgenin attenuates neuropathic pain in CCI rats by inhibiting
      activation of the p38 MAPK and NF-kappaB signaling pathways. These results
      implicate diosgenin in the treatment of neuropathic pain, which merits further
      clinical investigation.

PMID- 29067450
TI  - Clinical implications of vasohibin-1 in esophageal carcinoma cells: Inhibition of
      cell growth and migration.
AB  - As one of the first-established negative feedback regulators of angiogenesis,
      mesenchymal vasohibin-1 (VASH1) serves important roles in the progression and
      prognosis of various types of tumor. However, the clinical implications of VASH1
      in esophageal carcinoma (EC) cells have not been reported and the direct effects
      of VASH1 on EC cells remain unknown. In the present study, the expression of
      VASH1 in EC cells was observed using immunohistochemistry and western blotting; a
      chi2 test was used to analyze the correlation of VASH1 with clinical parameters,
      and it was observed that VASH1 was negatively-correlated with tumor size (r=
      0.399; P<0.01) and invasion depth (r=-0.318; P<0.01). Survival analysis
      demonstrated that VASH1 was positively-correlated with increased overall survival
      (P=0.039) and disease free survival (P=0.012). The direct effects of VASH1 on EC
      cells were analyzed by altering VASH1 expression, and it was observed that
      downregulation of VASH1 increased proliferation, clone formation and the
      migratory ability of EC9706 cells, whereas upregulation of VASH1 inhibited
      proliferation, clone formation and the migratory ability of EC1 cells. The
      results of the present study demonstrated that VASH1 in EC cells was negatively
      correlated with progression and poor prognosis of patients with EC. VASH1 was
      able to directly inhibit the growth and migration of EC cells.

PMID- 29067451
TI  - Roles of gangliosides in the differentiation of mouse pluripotent stem cells to
      neural stem cells and neural cells (Review).
AB  - Glycosphingolipids are important components of the outer layer of the plasma
      membrane in the majority of eukaryotic cells. Specifically, gangliosides are
      sialic acid-containing glycosphingolipids that participate in cell-cell
      recognition, adhesion, proliferation, differentiation and signal transduction,
      and are integral components of cell surface microdomains and lipid rafts. Stem
      cells are defined functionally as cells that have the capacity to self-renewal
      and differentiate to generate various cell types. Due to different synthesis
      patterns and locations of gangliosides, they have been used as molecular markers
      of stem cells. The current review describes the presence of gangliosides in
      various types of mouse stem cells, including pluripotent stem cells (embryonic
      stem cells and induced pluripotent stem cells) and neural stem cells, and the
      functional roles of gangliosides in various processes, including cell
      proliferation and neural differentiation. Thus, this review will aid the
      understanding of gangliosides patterns and functions in mouse stem cells, and
      outline markers for the identification of stem cells.

PMID- 29067452
TI  - Synergistic regulatory effects of microRNAs on brain glioma cells.
AB  - Glioma is among the most common types of cancer of the central nervous system and
      is difficult to cure. Due to the lack of glioma-specific treatments, patients
      with glioma exhibit high mortality rates. MicroRNAs (miRNAs) participate in the
      pathogenesis of glioma, and upregulation of specific miRNAs promotes cell
      proliferation, whereas apoptosis-inducing miRNAs are markedly downregulated in
      the context of glioma. Therefore, miRNAs may be important contributors to the
      pathogenesis of glioma. In the present study, nine miRNAs were investigated as
      miRNA-miRNA pairs, and the measured cell viabilities were consistent with the
      results of synergy predictions. Extensive synergy occurred among upregulated
      miRNAs in U87 cells, whereas downregulated miRNAs rarely exhibited synergism.
      Treatment with an miRNA-miRNA pair exhibiting strong synergy increased the
      inhibitory effects of these miRNAs on tumor cells, and the combined inhibitory
      effects were increased compared with the sum of the individual inhibitory effects
      of each miRNA. Using cell viability assays, TUNEL staining, and flow cytometry,
      the present study demonstrates that cotransfection with miR-20a and miR
      21inhibitors resulted in the highest synergistic effect on the promotion of
      apoptosis in U87 cells. The results of the present study provide important
      insights into the potential use of miRNAs in the treatment of glioma.

PMID- 29067454
TI  - Estradiol postconditioning relieves ischemia/reperfusion injury in axial skin
      flaps of rats, inhibits apoptosis and alters the MKP-1/ERK pathway.
AB  - Previous studies have suggested that estradiol can reduce the
      ischemia/reperfusion (I/R) injury in skin flaps. However, the mechanism,
      particularly the signal pathways involved in this protective effect are not well
      established. In the current study, an I/R injury model was established in rats to
      explore the connection between estradiol protection during I/R injury and
      extracellular signal-regulated kinase (ERK) signaling. Healthy male Wistar rats
      were divided into five groups (n=10): Control group (group I), I/R group (group
      II), saline group (group III), estradiol group (group IV) and inhibitor (PD
      98059) group (group V). The survival rate of the flap was compared between
      groups, morphological changes were observed by hematoxylin and eosin staining of
      sections, and terminal deoxynucleotidyl transferase dUTP nick end labeling was
      performed to identify apoptotic cells and determine the apoptotic index. To
      further investigate the mechanism, western blot analysis was performed to assess
      the protein level of ERK1/2, phospho-ERK1/2, and mitogen-activated protein kinase
      phosphatase 1 (MKP-1). The results of the present study demonstrated that
      estradiol therapy can reduce I/R injury and decrease the apoptosis index in an
      axial skin flap model. The inhibitor of the ERK pathway (PD-98059) partially
      abolished the effects of estradiol, which involve the phosphatase enzyme MKP-1.
      Taken together, the findings of the present study indicate that estradiol may act
      by reducing the expression of MKP-1, mediating the expression/activation changes
      of the ERK pathway and subsequently reduce the level of apoptosis and the I/R
      injury the axial flap. Estrogen may be used to mitigate the adverse reaction
      caused by ischemia-reperfusion injury and effectively improve the survival rate
      and survival quality of free skin flap and improve patient prognosis.

PMID- 29067453
TI  - Inhibitory effect of hyperoside isolated from Zanthoxylum bungeanum leaves on
      SW620 human colorectal cancer cells via induction of the p53 signaling pathway
      and apoptosis.
AB  - The present study aimed to demonstrate the antiproliferative effect of hyperoside
      from Zanthoxylum bungeanum leaves (HZL) and explain the underlying molecular
      mechanisms in the SW620 human colorectal cancer cell line. The cytotoxic effects
      of HZL were determined using a3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium
      bromide assay. Apoptosis and cell cycle were detected using flow cytometry.
      Reactive oxygen species (ROS) levels and mitochondrial membrane potential (?Psim)
      were assessed using 2',7'-dichlorofluorescin diacetate and 5,5',6,6'-tetrachloro
      1,1',3,3'-tetraethylbenzimidazolyl carbocyanine iodide fluorescence
      spectrophotometry, respectively. Western blot analysis was used to quantify the
      expression levels of apoptosis-associated proteins. Reverse transcription
      quantitative polymerase chain reaction analysis was used to determine the mRNA
      expression of glutathione peroxidase (GSH-Px) and catalase (CAT). HZL had a
      marked anti-proliferative effect on the SW620 human colorectal cancer cells by
      inducing cell cycle G2/M phase arrest and apoptosis, which was associated with an
      increase in the expression of p53 and p21. Further mechanistic investigations
      revealed that the induction of apoptosis was associated with increased generation
      of ROS, reduced ?Psim, and upregulation of B-cell lymphoma 2-associated X
      protein, cytochrome c, caspase-9, apoptotic protease activating factor 1 and
      caspase-3. The antitumor potency of HZL was also attributed to inhibition of the
      mRNA expression levels of GSH-Px and CAT. These data indicated that HZL may be
      involved in the pro-apoptotic signaling of SW620 human colorectal cancer cells
      via induction of the caspase-dependent apoptosis and p53 signaling pathways.

PMID- 29067455
TI  - Hyperbaric oxygen alleviates the activation of NLRP-3-inflammasomes in traumatic
      brain injury.
AB  - Growing evidence has demonstrated that the nucleotide-binding oligomerization
      domain-like receptor family pyrin domain containing 3 (NLRP-3) inflammasome
      mediated inflammatory pathways have been involved in the secondary injury of
      traumatic brain injury (TBI). In the present study, the authors investigated the
      effects of hyperbaric oxygen (HBO) therapy on the NLRP-3 inflammasome pathway
      following TBI. Following the evaluation of motor deficits and brain edema, the
      therapeutic effects of HBO on interleukin (IL)-1beta and IL-18 expression were
      assessed, as well as NLRP-3 inflammasome activation following TBI. HBO may
      improve motor score and reduce brain edema, accompanied with the reduction of IL
      1beta and IL-18 during the 7-day observation period. Furthermore, HBO suppressed
      mRNA and protein expression of NLRP-3-inflammasome components, especially
      reducing NLRP-3 expression in microglia. Thus, these results suggested that HBO
      alleviates the inflammatory response in experimental TBI via modulating
      microglial NLRP-3-inflammasome signaling.

PMID- 29067457
TI  - MicroRNA-613 inhibits proliferation and invasion of renal cell carcinoma cells
      through targeting FZD7.
AB  - MicroRNAs (miRNAs) have emerged as critical regulators in cancer progression. miR
      613 has been reported as a tumor suppressor gene in many types of human cancers.
      However, the function of miR-613 in renal cell carcinoma (RCC) remains unclear.
      In the present study, the authors aimed to detect the expression of miR-613 and
      its function in RCC cell lines. miR-613 was reported to be significantly
      downregulated RCC cell lines. Functional analyses demonstrated that
      overexpression of miR-613 significantly decreased RCC cell proliferation and
      invasion. Bioinformatics analysis showed that Frizzled7 (FZD7) was a predicted
      target of miR-613, which was verified by dual-luciferase reporter assay, reverse
      transcription quantitative-polymerase chain reaction and western blot analysis.
      Restoration of FZD7 significantly reversed the suppressive effects of miR-613 on
      RCC cell proliferation and invasion. Taken together, the results of the present
      study indicated that miR-613 functions as a tumor suppressor that inhibits RCC
      cell proliferation and invasion by targeting and inhibiting FZD7, providing novel
      insight into RCC pathogenesis and a potential therapeutic target for RCC.

PMID- 29067456
TI  - Effects of Shu Gan Jian Pi formula on rats with carbon tetrachloride-induced
      liver fibrosis using serum metabonomics based on gas chromatography-time of
      flight mass spectrometry.
AB  - Liver fibrosis is a common stage in the majority of chronic liver diseases,
      regardless of the etiology, and its progression may lead to hepatic cirrhosis or
      hepatocellular carcinoma. Metabolomics, a powerful approach in systems biology,
      is a discipline used to qualitatively and quantitatively analyze the small
      molecule metabolites of cells at specific times and under certain conditions. The
      present study aimed to investigate serum metabolic changes following Shu Gan Jian
      Pi formula (SGJPF) treatment of carbon tetrachloride (CCl4)-induced liver
      fibrosis in rats using gas chromatography-time of flight mass spectrometry (GC
      TOFMS). In addition, the potential mechanisms were explored. Rat liver fibrosis
      was induced by twice-weekly subcutaneous CCl4 injection for 12 continuous weeks.
      During the same period, the SGJPF group received 16.2 g/kg body weight SGJPF,
      diluted in water, once a day for 12 weeks. Rats in the control and model groups
      received oral administration of the same volume of saline solution. Serum samples
      from the control, model and SGJPF groups were collected after 12 weeks of
      treatment, and metabolic profile alterations were analyzed by GC-TOF/MS.
      Metabolic profile analysis indicated that clustering differed between the three
      groups and the following 12 metabolites were detected in the serum of all three
      groups: Isoleucine; L-malic acid; D-erythro-sphingosine; putrescine; malonic
      acid; 3,6-anhydro-D-galactose, alpha-ketoglutaric acid; ornithine; glucose;
      hippuric acid; tetrahydrocorticosterone; and fucose. The results demonstrated
      that SGJPF treatment mitigated the effects of CCl4-induced liver fibrosis on
      biomarker levels, thus indicating that SGJPF may have a therapeutic effect on
      CCl4-induced liver fibrosis in rats. The mechanism may involve the regulation of
      energy, amino acid, sphingolipid, cytochrome P450, glucose and water-electrolyte
      metabolism.

PMID- 29067458
TI  - Associations between mutations of the cell cycle checkpoint kinase 2 gene and
      gastric carcinogenesis.
AB  - Gastric cancer is the most common malignant tumor of the digestive system. The
      etiology of gastric cancer is complex, and susceptibility at the genetic level
      remains to be fully elucidated in genetic investigations. In the present study,
      mutations of the cell cycle checkpoint kinase 2 (CHEK2) gene and its association
      with gastric cancer were examined. Reverse transcription-quantitative polymerase
      chain reaction technology was used to detect the expression of CHEK2 and it was
      found that the expression of CHEK2 was low in gastric cancer. Using sequencing
      analysis, it was found that the low expression level of CHEK2 was associated with
      expression of its mutation. The present study also established a CHEK2
      overexpressing mutant and confirmed that CHEK2 promoted gastric cancer cell
      proliferation. Overexpression of the CHEK2 mutation was confirmed to promote
      cancer cell migration and invasion. Furthermore, western blot analysis results
      revealed that overexpression of the CHEK2 mutation downregulated E-cadherin and
      upregulated vimentin expression, indicating the mechanism underlying the altered
      biological behavior. These results suggested that there was a correlation between
      mutation of the CHEK2 gene and gastric cancer, and provided an experimental basis
      for antitumor drug investigation and development according to its mutation
      target.

PMID- 29067459
TI  - MicroRNA-329 serves a tumor suppressive role in colorectal cancer by directly
      targeting transforming growth factor beta-1.
AB  - Colorectal cancer (CRC) is the third most common type of diagnosed cancer and the
      fourth leading cause of cancer-associated mortalities worldwide. Increasing
      studies have demonstrated that the deregulation of microRNAs (miRNAs or miRs) is
      associated with the occurrence and development of multiple types of human cancer,
      including CRC. miR-329 has been identified to be downregulated in various types
      of cancer; however, its expression pattern, functions and mechanisms in CRC
      remain unclear. The present study demonstrated that miR-329 was lowly expressed
      in CRC tissue samples and cell lines. Low expression of miR-329 was correlated
      with tumor-node-metastasis stage and lymph node metastasis in patients with CRC.
      In vitro experiments revealed that resumption expression of miR-329 suppressed
      cell proliferation and invasion in CRC. Furthermore, the results of the present
      study indicated that miR-329 targets transforming growth factor-beta1 (TGF-beta1)
      directly in vitro. TGF-beta1 was demonstrated to be upregulated in CRC tissue
      samples and inversely correlated with miR-329 expression. Upregulation of TGF
      beta1 was able to partially counteract the antitumor roles of miR-329 on CRC cell
      proliferation and invasion. The results of the current study revealed that miR
      329 suppresses CRC cell proliferation and invasion through targeting TGF-beta1,
      thus suggesting that targeting miR-329/TGF-beta1 may provide a novel effective
      therapeutic approach for the treatment of patients with CRC.

PMID- 29067460
TI  - STRA6 as a possible candidate gene for pathogenesis of osteoporosis from RNA-seq
      analysis of human mesenchymal stem cells.
AB  - To identify novel candidate genes associated with osteoporosis, RNA-sequence
      analysis of human mesenchymal stem cells (hMSCs) from patients with osteoporosis
      (G3) and osteopenia (G2), and healthy controls (G1) was performed. Differentially
      expressed genes (DEGs) from among the three groups were identified. DEGs were
      separated into nine groups according to their gene expression patterns: UU (up
      and up), UF (up and flat), UD (up and down), FU (flat and up), FF (flat and
      flat), FD (flat and down), DU (down and up), DF (down and flat), and DD (down and
      down). Among the 42 DEGs between G3 and G1, eight candidate genes, namely
      stimulated by retinoic acid 6 (STRA6), melanophilin, neurotrophic receptor
      tyrosine kinase 2, cartilage oligomeric matrix protein, collagen type XI alpha 1
      chain, integrin subunit beta 2, monooxygenase DBH-like 1 and selenoprotein P,
      were selected, as they demonstrated consistent gene expression patterns of UU,
      FU, FD, and DD. Among these eight genes, STRA6 was highly expressed in the
      osteoporosis group and based on additional data from quantitative polymerase
      chain reaction analysis, it was selected for further study. In order to
      investigate whether STRA6 served a functional role in osteoblast or adipocyte
      differentiation, the effects of STRA6 expression changes in pluripotent stem cell
      C3H10T1/2, preosteoblast MC3T3-E1 and stromal ST2 cell lines were examined. Bone
      morphogenetic protein 2 enhanced STRA6 expression only at the early stage of
      osteoblast differe-ntiation, and overexpression of STRA6 temporally inhibited the
      expression of osteoblastogenesis markers, including runt related transcription
      factor 2, bone sialoprotein and osteocalcin. Furthermore, the knockdown of STRA6
      slightly enhanced nodule formation at the late stage of osteoblast
      differentiation, and overexpression of STRA6 in ST2 cells enhanced adipocyte
      differentiation. Taken together, STRA6 expression could be associated with the
      pathogenesis of osteoporosis by promoting adipocyte differentiation over
      osteoblast differentiation in the hMSC population.

PMID- 29067462
TI  - The transfection of A20 gene prevents kidney from ischemia reperfusion injury in
      rats.
AB  - Ischemia/reperfusion may induce inflammation and cell death through the nuclear
      factor (NF)-kappaB signaling pathway. As a negative regulator of NF-kappaB, zinc
      finger A20 exhibits anti-apoptotic and anti-inflammatory effects in vitro. The
      present study was designed to upregulate A20 expression using an A20 transfection
      approach to investigate the in vivo protective effects of the A20 gene on renal
      ischemia reperfusion injury. The A20 gene was cloned into a pcDNA3.1 vector to
      construct the expression plasmid pcDNA3.1-A20. The plasmid was wrapped with a
      liposome and injected intravenously into rats 48 h prior to establishing the
      models of renal ischemia reperfusion injury. Saline and the empty plasmid
      pcDNA3.1 were used as controls. Following 24 h post-operation, A20 expression was
      determined using reverse transcription-quantitative polymerase chain reaction and
      western blotting. The renal function and structure were assessed by analyzing the
      concentrations of serum creatinine (Scr), blood urea nitrogen (BUN) and
      histological features. Renal tissues were additionally examined for renal tubular
      cell apoptosis and NF-kappaB activity. The results demonstrated that in vivo
      transfection of pcDNA3.1-A20 induced renal A20 expression in rats. A20
      overexpression in vivo significantly reduced renal injury as demonstrated by the
      improved levels of Scr and BUN and the reduction in histological damage. These
      improvements were accompanied by a suppression of renal proximal tubular
      epithelial cell apoptosis and an inhibition of NF-kappaB activity. These results
      indicated that transfection of the A20 gene upregulates the expression of A20 in
      vivo and protects the kidneys from ischemia reperfusion injury via inhibition of
      the NF-kappaB signal transduction pathway.

PMID- 29067461
TI  - Mori Folium water extract alleviates articular cartilage damages and inflammatory
      responses in monosodium iodoacetate-induced osteoarthritis rats.
AB  - Mori folium, the leaf of Morus alba L. (Moraceae), has been widely used in
      traditional medicine for the treatment of various diseases. It has been recently
      reported that Mori folium possesses potential chondroprotective effects in
      interleukin (IL)-1beta-stimulated human chondrocytes; however, its protective and
      therapeutic potential against osteoarthritis (OA) in an animal model remains
      unclear. In this study, as part of an ongoing screening program to evaluate the
      anti-osteoarthritic potential of Mori folium, the protective effects of a water
      extract of Mori folium (MF) on cartilage degradation and inflammatory responses
      in a monosodium iodoacetate (MIA)-induced OA rat model were evaluated. The
      results demonstrated that administration of MF had a tendency to attenuate the
      damage to articular cartilage induced by MIA, as determined by knee joint
      swelling and the histological grade of OA. The elevated levels of matrix
      metalloproteinases-13 and two bio-markers for the diagnosis and progression of
      OA, such as the cartilage oligomeric matrix protein and C-telopeptide of type II
      collagen, were markedly ameliorated by MF administration in MIA-induced OA rats.
      In addition, MF significantly suppressed the production of pro-inflammatory
      cytokines, including IL-1beta, IL-6 and tumor necrosis factor-alpha. MF also
      effectively inhibited the expression of inducible nitric oxide (NO) synthase and
      cyclooxygenase-2, thus inhibiting the release of NO and prostaglandin E2.
      Although further work is required to fully understand the critical role and
      clinical usefulness, these findings indicate that MF may be a potential
      therapeutic option for the treatment of OA.

PMID- 29067463
TI  - IGFBP-rP1 acts as a potential tumor suppressor via the suppression of ERK
      signaling pathway in endometrial cancer cells.
AB  - Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a
      potential tumor-suppressor gene in various cancers. However, its biological role
      and underlying mechanism has not been well investigated in endometrial cancer
      yet. The aim of the present study aimed to investigate the role and underlying
      molecular mechanisms of IGFBP-rP1 in endometrial cancer cells in vitro. The
      authors used transfection of IGFBP-rP1 or small interfering (si)RNA in
      endometrial cancer HEC-1A or Ishikawa cells, respectively. Biological functional
      alterations, such as cell growth and cell cycle were analyzed in endometrial
      cancer cells, combined with the use of PD98059. A panel of proteins including
      phospho-retinoblastoma (p-RB) and p-extracellular signal-regulated kinase
      (ERK)/ERK were detected by western blot analysis. It was observed that IGFBP-rP1
      transfection inhibited cell growth, and induced G1 phase arrest and cellular
      senescence in HEC-1A cells while gene silencing presented the adverse functional
      changes. Moreover, p-RB and p-ERK were significantly downregulated or upregulated
      in HEC-1A-IGFBP-rP1 cells or Ishikawa-siRNA (IGFBP-rP1) compared with control
      cells, respectively. These observations were reinforced in endometrial cancer
      cells by PD98059 treatment. The authors conclude that IGFBP-rP1 acts as a
      potential tumor suppressor via the suppression of the ERK signaling pathway in
      endometrial cancer cells. These findings suggested that IGFBP-rP1 may serve as a
      potential therapeutic target for cancer intervention in the future.

PMID- 29067464
TI  - Protective effect of berberine on renal fibrosis caused by diabetic nephropathy.
AB  - Berberine (BBR) is a material extracted from Chinese herbs, which has been used
      in the treatment of diabetes in Chinese medicine for thousands of years. However,
      the importance of BBR in renal fibrosis remains to be elucidated. In the present
      study, streptozotocin-induced diabetic nephropathy (DN) rats were used to
      determine the effect of BBR on renal fibrosis. The pathology of the kidneys was
      examined using periodic acid-Schiff (PAS) and Masson staining. The expression
      levels of transforming growth factor-beta (TGF-beta) and alpha smooth muscle
      actin (alpha-SMA) in kidneys were observed using immunohistochemical staining.
      The mRNA and protein expression levels of TGF-beta, alpha-SMA, vimentin, nuclear
      factor-kappaB were examined using reverse transcription-quantitative polymerase
      chain reaction and western blotting, respectively. PAS and Masson staining
      revealed that there was notable glomerular hypertrophy and mesangial matrix
      expansion in DN rats. Immunohistochemistry revealed that there was a significant
      increase in TGF-beta and alpha-SMA expression levels in the renal
      tubulointerstitium and the extracellular matrix. However, treatment with BBR may
      significantly reduce kidney injury. The protein and mRNA expression levels of TGF
      beta, vimentin and alpha-SMA were significantly increased in DN rats compared
      with the control group; however, this increase was reduced following treatment
      with BBR. The present study revealed that BBR may inhibit fibrosis and ameliorate
      the symptoms of DN. The current findings indicated that BBR may be used as a
      potential treatment for patients with DN.

PMID- 29067465
TI  - Molecular mechanisms and potential prognostic effects of REST and REST4 in glioma
      (Review).
AB  - Glioma refers to a tumor of the brain and central nervous system, which is
      characterized by high incidence, high mortality and high recurrence rate.
      Although the association between glioma and the repressor element silencing
      transcription factor (REST) has been reported by numerous studies, the
      complicated regulatory mechanisms underlying REST remain unknown. REST is a
      transcriptional repressor that undergoes alternative splicing to produce splicing
      variants when transcribed. Previous studies have demonstrated that alternative
      splicing may serve a role in the outcome of glioma. The present review discussed
      the mutual relationship among REST, REST4 and glioma. It was concluded that
      increased REST expression in glioma may be associated with poor prognosis; and
      REST4, an AS variant of REST, also functions to regulate glioma by suppressing
      REST. In addition, the present review discussed the regulation of REST and its
      target genes in glioma, and identified factors that induce REST alternative
      splicing, particularly in glioma. These findings suggest that REST may be
      considered a prognostic factor, which can be predictive of patient outcome.

PMID- 29067466
TI  - miR-128 enhances dendritic cell-mediated anti-tumor immunity via targeting of
      p38.
AB  - MiRNA (miR)-128, which is a well-recognized inhibitor of tumor growth, is
      involved in the anti-tumor function of dendritic cells (DCs). However, the
      association between miR-128 and the DC-mediated anti-tumor immunity remains to be
      elucidated. Murine B16 melanoma cells and C57BL/6 male mice were used to obtain
      marrow-derived DCs. DCs were treated with B16 cell suspension. miR-128 mimic, miR
      128 inhibitor, p38 inhibitor or negative control oligonucleotides were
      transfected into DCs. After transfection, mRNA and protein expression of p38 in
      DCs was detected via reverse transcription-quantitative polymerase chain reaction
      and western blotting. The present study demonstrated that the miR-128 abundance
      in DCs was significantly attenuated by B16 (a melanoma cell line) stimulation and
      the protein expression level of p38 was increased. Additionally, miR-128
      inhibited the protein expression of p38 in DCs in a dose-dependent manner,
      however no significant effect on the p38 mRNA level was observed. Furthermore,
      miR-128 mimic or p38 inhibitor decreased the mRNA expression and secretion of
      interleukin (IL)-6 and IL-10 cytokines and increased the level of IL-12 in DCs,
      whereas an miR-128 inhibitor exhibited the opposite effects. These findings
      suggested that miR-128 regulated the immune response of DCs via p38-downstream
      cytokines. Furthermore, the tumor growth rate, size and weight were markedly
      decreased and the survival time prolonged, following injection of DCs harboring
      miR-128 mimic or p38 inhibitor in C57BL/6 mice bearing B16 melanoma. The results
      therefore suggest that miR-128 enhances the anti-tumor immunity response of DCs
      via targeting of the p38 mitogen activated protein kinase signaling pathway.

PMID- 29067467
TI  - Analysis of microbial community composition and diversity in postoperative
      intracranial infection using high-throughput sequencing.
AB  - Intracranial infection is one of the most serious complications following
      neurosurgery. It is well acknowledged that bacteria and fungi are the main
      pathogens responsible for postoperative intracranial infection. However, the
      microbial community structure, including composition, abundance and diversity, in
      postoperative intracranial infection is not fully understood, which greatly
      compromises our understanding of the necessity and effectiveness of postoperative
      antibiotic treatment. The present study collected eight cerebrospinal fluid (CSF)
      samples from patients with intracranial infection following neurosurgical
      procedures. High-throughput amplicon sequencing for 16S rDNA and internal
      transcribed spacer (ITS) was performed using the Illumina MiSeq platform to
      investigate the microbial community composition and diversity between treated and
      untreated patients. Bioinformatics analysis revealed that the microbial
      composition and diversity in each patient group (that is, with or without
      antibiotic treatment) was similar; however, the group receiving antibiotic
      treatment had a comparatively lower species abundance and diversity compared with
      untreated patients. At the genus level, Acinetobacter and Staphylococcus were
      widely distributed in CSF samples from patients with postoperative intracranial
      infection; in particular, Acinetobacter was detected in all CSF samples. In
      addition, five ITS fungal libraries were constructed, and Candida was detected in
      three out of four patients not receiving antibiotic treatment, indicating that
      the fungal infection should be given more attention. In summary, 16S and ITS high
      throughput amplicon sequencing were practical methods to identify pathogens in
      the different periods of treatment in patients with postoperative intracranial
      infection. There was a notable difference in microbial composition and diversity
      between the treated and untreated patients. Alterations in the microbial
      community structure may provide a signal whether antibiotic treatment worked in
      postoperative intracranial infection and may assist surgeons to better control
      the progression of infection.

PMID- 29067468
TI  - Resveratrol improves urinary dysfunction in rats with chronic prostatitis and
      suppresses the activity of the stem cell factor/c-Kit signaling pathway.
AB  - Chronic prostatitis (CP) is a common urological disorder, with bladder voiding
      dysfunction being the primary clinical manifestation. Resveratrol is polyphenolic
      compound isolated from numerous plants, with widely-reported anti-inflammatory
      properties. The present study aimed to investigate whether resveratrol may
      improve overactive bladder in rats with CP and to investigate the underlying
      molecular mechanisms. Furthermore, the potential pharmacological synergy between
      resveratrol and solifenacin was also investigated as a potential treatment for
      CP. Following the successful establishment of a rat model of CP by subcutaneously
      injecting DPT vaccine, rats were treated with resveratrol or a combination of
      resveratrol + solifenacin. Bladder pressure and volume tests were performed to
      investigate the effect of resveratrol and solifenacin on urinary dysfunction in
      rats with chronic prostatitis. Western blot analysis and immunohistochemical
      staining were used to examine the expression of c-Kit receptor, stem cell factor
      (SCF), AKT and phosphorylated-AKT (p-AKT) in the bladder tissue. The results of
      the bladder pressure and volume test indicated that the maximum capacity of the
      bladder, residual urine volume and maximum voiding pressure in the control group
      were 0.57 ml, 0.17 ml and 29.62 cm H2O, respectively. These values were increased
      by 71, 27 and 206% in rats in the CP group compared with the control group.
      Following treatment with resveratrol, the results in the resveratrol group were
      reduced by 25.77, 44.23 and 13.32% compared with the CP group. The results of
      western blot analysis, immunohistochemical staining and immunofluorescence
      labeling demonstrate that the protein expression of SCF, c-Kit and p-AKT in the
      bladder of rats in the CP group was 4.32, 6.13 and 6.31 times higher compared
      with the control group, respectively. Following treatment with resveratrol,
      protein expression was significantly reduced. However, no significant differences
      were observed between the protein expression of the SCF, c-Kit and p-AKT in the
      bladder between the resveratrol and combination groups. In conclusion,
      resveratrol may improve overactive bladder by downregulating the protein
      expression of SCF, c-Kit and p-AKT in the bladder of rats with CP. Furthermore, a
      combination of resveratrol and solifenacin may have potential pharmacological
      synergy as a treatment for patients with CP.

PMID- 29067469
TI  - Long non-coding RNA AK001796 contributes to cisplatin resistance of non-small
      cell lung cancer.
AB  - Cisplatin (DDP)-based chemotherapy is the most widely used therapy for non-small
      cell lung cancer (NSCLC). However, the existence of chemoresistance has become a
      major limitation in its efficacy. Long non-coding RNAs (lncRNAs) have been shown
      to be involved in chemotherapy drug resistance. The aim of the present study was
      to investigate the biological role of lncRNA AK001796 in cisplatin-resistant
      NSCLC A549/DDP cells. Reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) analysis was performed to monitor the differences in the
      expression of AK001796 in cisplatin-resistant (A549/DDP) cells and parental A549
      cells. Cellular sensitivity to cisplatin and cell viability were examined using
      an MTT assay. Cell apoptosis and cell cycle distribution were measured using flow
      cytometry. The expression levels of cell cycle proteins cyclin C (CCNC),
      baculoviral IAP repeat containing 5 (BIRC5), cyclin-dependent kinase 1 (CDK1) and
      G2 and S phase-expressed 1 (GTSE1) were assessed using RT-qPCR and western blot
      analyses. It was found that the expression of AK001796 was increased in A549/DDP
      cells, compared with that in A549 cells. The knockdown of AK001796 by small
      interfering RNA reduced cellular cisplatin resistance and cell viability, and
      resulted in cell-cycle arrest, with a marked increase in the proportion of
      A549/DDP cells in the G0/G1 phase. By contrast, the knockdown of AK001796
      increased the number of apoptotic cancer cells during cisplatin treatment. It was
      also shown that the knockdown of AK001796 positively induced the expression of
      cell apoptosis-associated factors, CCNC and BIRC5, and suppressed the expression
      of cell cycle-associated factors, CDK1 and GTSE5. Taken together, these findings
      indicated that lncRNA AK001796 increased the resistance of NSCLC cells to
      cisplatin through regulating cell apoptosis and cell proliferation, and thus
      provides an attractive therapeutic target for NSCLC.

PMID- 29067472
TI  - A Novel and More Aesthetic Injection Pattern for Malar Cheek Volume Restoration.
AB  - The loss of superior midface contour and projection can be corrected with the use
      of injectable hyaluronic acid (HA) dermal fillers, however, the most frequently
      used injection pattern employs a technique which was originally designed for
      malar implant surgery. Here we describe a novel injection pattern for restoring
      facial contours with a HA dermal filler inspired by traditional make-up artistry,
      which includes greater superolateral positioning of injection sites. Importantly,
      this technique helps injectors avoid creating an excess of volume in the anterior
      portion of the malar complex. Contributing authors/injectors, who now use this
      technique exclusively, have found that it has so far provided optimal aesthetic
      results for hundreds of patients with no observables complications. The malar
      cheek contributes much to the aesthetic curvature of the face and deserves a
      thoughtful update for injectable HA, as the traditional technique has never
      actually been aligned with its medium. In the experience of the contributing
      authors, this technique helps achieve a greater aesthetic outcome in the
      correction of midface contour deficiencies and has consistently resulted in high
      patient satisfaction. Level of Evidence IV This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 .

PMID- 29067471
TI  - The Incidence of Psychiatric Medication Use and Its Effect on Intraoperative
      Bleeding in Facial Cosmetic Patients.
AB  - PURPOSE: Psychiatric medications, particularly the selective serotonin reuptake
      inhibitors, have been associated with increased surgical bleeding. This study
      aims to compare intraoperative surgical bleeding between cosmetic surgery
      patients who are and are not taking psychiatric medications. METHODS: The charts
      of 392 consecutive patients who underwent cosmetic facial surgery at the senior
      author's practice were reviewed. Independent variables included self-reported
      psychiatric history, psychiatric diagnoses, and psychiatric medications as
      documented in the preoperative history and physical examination. The primary
      endpoint was administration of desmopressin (DDAVP), our proxy for increased
      surgical bleeding. Significant predictors of these endpoints were determined via
      Chi-squared testing. RESULTS: One hundred and seventeen patients had a
      psychiatric diagnosis (30%), and 129 patients were taking some class of
      psychiatric medication (33%). Seventy-two patients received DDAVP (18%). A
      psychiatric diagnosis did not predict DDAVP administration (14.3% for patients
      with a psychiatric diagnosis vs. 20.88% for those without, p = 0.14). The use of
      a psychiatric medication was not associated with DDAVP administration (14.7 vs.
      21%, p = 0.14). Male gender significantly predicted DDAVP administration (27.8
      vs. 16.9% for females, p = 0.04). CONCLUSION: The use of psychiatric medications
      does not predict increased intraoperative surgical bleeding. This is useful given
      the prevalence of psychiatric medication use among this patient population and
      obviates the need for discontinuation of these medications, which otherwise could
      be consequential. LEVEL OF EVIDENCE IV: This journal requires that authors assign
      a level of evidence to each article. For a full description of these Evidence
      Based Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 29067470
TI  - Multiple microRNAs function as self-protective modules in acetaminophen-induced
      hepatotoxicity in humans.
AB  - Acetaminophen (APAP) overdose is the leading cause of acute liver failure. Yet
      the mechanisms underlying adaptive tolerance toward APAP-induced liver injury are
      not fully understood. To better understand molecular mechanisms contributing to
      adaptive tolerance to APAP is an underpinning foundation for APAP-related
      precision medicine. In the current study, the mRNA and microRNA (miRNA)
      expression profiles derived from next generation sequencing data for APAP-treated
      (5 and 10 mM) HepaRG cells and controls were analyzed systematically. Putative
      miRNAs targeting key dysregulated genes involved in APAP hepatotoxicity were
      selected using in silico prediction algorithms, un-biased gene ontology, and
      network analyses. Luciferase reporter assays, RNA electrophoresis mobility shift
      assays, and miRNA pull-down assays were performed to investigate the role of
      miRNAs affecting the expression of dysregulated genes. Levels of selected miRNAs
      were measured in serum samples obtained from children with APAP overdose (58.6
      559.4 mg/kg) and from healthy controls. As results, 2758 differentially expressed
      genes and 47 miRNAs were identified. Four of these miRNAs (hsa-miR-224-5p, hsa
      miR-320a, hsa-miR-449a, and hsa-miR-877-5p) suppressed drug metabolizing enzyme
      (DME) levels involved in APAP-induced liver injury by downregulating HNF1A, HNF4A
      and NR1I2 expression. Exogenous transfection of these miRNAs into HepaRG cells
      effectively rescued them from APAP toxicity, as indicated by decreased alanine
      aminotransferase levels. Importantly, hsa-miR-320a and hsa-miR-877-5p levels were
      significantly elevated in serum samples obtained from children with APAP overdose
      compared to health controls. Collectively, these data indicate that hsa-miR-224
      5p, hsa-miR-320a, hsa-miR-449a, and hsa-miR-877-5p suppress DME expression
      involved in APAP-induced hepatotoxicity and they contribute to an adaptive
      response in hepatocytes.

PMID- 29067473
TI  - The dawn of "immune-revolution" in children: early experiences with checkpoint
      inhibitors in childhood malignancies.
AB  - Modern immunotherapy with checkpoint inhibitors has changed clinical practice of
      adult patients with advanced cancer. Blockade of CTLA-4 and PD-1 pathways have
      shown survival benefits in different diseases. In children, combination of
      surgery, radiotherapy and chemotherapy have improved survival rates of solid
      tumors. However, the outcomes for subsets of patients such as those with high
      grade, refractory, or metastatic disease remain extremely poor. Currently, the
      treatment of these patients is almost exclusively based on standard chemotherapy.
      The significant proportion of pediatric cancers with high number of mutations and
      subsequent high expression of neoantigens, together with the potential prognostic
      role of the immunosuppressive checkpoint molecules (CTLA-4, PD-L1) can represent
      a promising rationale that support the use of checkpoint inhibitors. We made a
      revision about emerging data regarding safety and activity of checkpoint
      inhibitors in children with solid tumors.

PMID- 29067475
TI  - ?

PMID- 29067476
TI  - [Introduction of the flat rate reimbursement system in Germany : A historical
      review].
AB  - With the new millenium, "Gesundsheitsreform 2000" (Health Reform 2000)
      fundamentally changed the principles for reimbursement of hospital treatment
      costs in Germany. Before then, hospital treatment was completely reimbursed by
      the health insurance companies. Now, reimbursement is entirely based on a new
      diagnosis-related group (DRG) payment system. The aim was a reduction of the
      expanding cost of the health care system, more efficient economics, and better
      control. This concept was unique, since until now reimbursement had nowhere been
      based 100% on a DRG system. For critical care medicine, this became a special
      problem because standardization of treatment procedures is nearly impossible and
      is not related to specific diagnoses. Therefore, completely new solutions had to
      be found for a fair reimbursement of critical care treatment. The difficult
      search for a good solution is described here. The DIVI (German Interdisciplinary
      Association of Critical Care and Emergency Medicine) was able to present good
      arguments and concepts based on actual and realistic cost analyses. However, the
      solutions found remain insufficient, and fundamental problems are still not
      solved.

PMID- 29067474
TI  - Restoring tibiofemoral alignment during ACL reconstruction results in better knee
      biomechanics.
AB  - PURPOSE: Anterior cruciate ligament (ACL) reconstruction (ACLR) aims to restore
      normal knee joint function, stability and biomechanics and in the long term avoid
      joint degeneration. The purpose of this study is to present the anatomic single
      bundle (SB) ACLR that emphasizes intraoperative correction of tibiofemoral
      subluxation that occurs after ACL injury. It was hypothesized that this technique
      leads to optimal outcomes and better restoration of pathological tibiofemoral
      joint movement that results from ACL deficiency (ACLD). METHODS: Thirteen men
      with unilateral ACLD were prospectively evaluated before and at a mean follow-up
      of 14.9 (SD = 1.8) months after anatomic SB ACLR with bone patellar tendon bone
      autograft. The anatomic ACLR replicated the native ACL attachment site anatomy
      and graft orientation. Emphasis was placed on intraoperative correction of
      tibiofemoral subluxation by reducing anterior tibial translation (ATT) and
      internal tibial rotation. Function was measured with IKDC, Lysholm and the Tegner
      activity scale, ATT was measured with the KT-1000 arthrometer and tibial rotation
      (TR) kinematics were measured with 3Dmotion analysis during a high-demand
      pivoting task. RESULTS: The results showed significantly higher TR of the ACL
      deficient knee when compared to the intact knee prior to surgery (12.2 degrees 
      +/- 3.7 degrees  and 10.7 degrees  +/- 2.6 degrees  respectively, P = 0.014).
      Postoperatively, the ACLR knee showed significantly lower TR as compared to the
      ACL-deficient knee (9.6 degrees +/-3.1 degrees , P = 0.001) but no difference as
      compared to the control knee (n.s.). All functional scores were significantly
      improved and ATT was restored within normal values (P < 0.001). CONCLUSIONS:
      Intraoperative correction of tibiofemoral subluxation that results after ACL
      injury is an important step during anatomic SB ACLR. The intraoperative
      correction of tibiofemoral subluxation along with the replication of native ACL
      anatomy results in restoration of rotational kinematics of ACLD patients to
      normal levels that are comparable to the control knee. These results indicate
      that the reestablishment of tibiofemoral alignment during ACLR may be an
      important step that facilitates normal knee kinematics postoperatively. LEVEL OF
      EVIDENCE: Level II, prospective cohort study.

PMID- 29067477
TI  - Circular RNA maps paving the road to biomarker development?

PMID- 29067478
TI  - [Embryonal malformation suggests malignant tumor in the tail of the pancreas].

PMID- 29067479
TI  - Highly sensitive aptamer based on electrochemiluminescence biosensor for label
      free detection of bisphenol A.
AB  - Bisphenol A (BPA), a typical endocrine disruptor, is widely used as a key monomer
      in the packaging industry. Residual monomer can transfer from the package
      material to the food and thereby pose a risk to the health of the consumer, so
      determination of BPA migration is highly important for food safety control. In
      this study, a simple but sensitive electrochemiluminescence (ECL) biosensor,
      which combines the characteristics of high selectivity of an aptamer and high
      sensitivity of ECL, has been developed to detect BPA from package materials. The
      aptamer was immobilized on a gold electrode surface through Au-S interaction. The
      aptamer was then hybridized with complementary DNA (CDNA) to form double-stranded
      DNA (dsDNA). Ru(phen)32+ can intercalate into the grooves of dsDNA and acts as an
      ECL indicator; high ECL intensity can therefore be detected from the electrode
      surface. In the presence of BPA, which can competitively bind with the aptamer
      owing to their high affinity, Ru(phen)32+ is released from the electrode surface
      and the ECL of the system is decreased. The decreasing ECL signal has a linear
      relationship with BPA in the range of 0.1-100 pM with a detection limit of 0.076
      pM. The developed biosensor has been applied to detect migration of BPA from
      different categories of canned drink with satisfactory results.

PMID- 29067480
TI  - Pattern recognition of 8-hydroxy-2'-deoxyguanosine in biological fluids.
AB  - 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative DNA damage, which
      has been used as a sensitive and reliable marker of oxidative stress and
      carcinogenesis, is found in high levels in biological fluids of leukemia
      patients. A reliable screening method based on pattern recognition of 8-OHdG
      using stochastic sensors designed with graphene materials decorated with
      nanoparticles of TiO2Ag or TiO2Au was developed. 5,10,15,20-Tetraphenyl-21H,23H
      porphyrin (P), 2,6-bis((E)-2-(furan-2-yl)vinyl)-4-(4,6,8-trimethylazulen-1
      yl)pyridine (Py1), and 2,6-bis((E)-2-(thiophen-3-yl)vinyl)-4-(4,6,8
      trimethylazulen-1-yl)pyridine (Py2) were used as modifiers of the graphene paste
      in the design of sensors. The screening method used for pattern recognition was
      developed for two pH values accordingly with the nature of the biological fluid
      to be screened: pH = 3.02 for urine samples and pH = 7.49 for whole blood
      samples. High sensitivities and low limits of determination for 8-OHdG obtained
      at both pH values favored the early detection of leukemia. Recoveries over 98.00%
      with RSD (%) values lower than 1.00% proved the reliability of the proposed
      screening method. Graphical abstract Graphene based sensors detect 8-hydroxy-2'
      deoxyguanosine in biological fluids.

PMID- 29067482
TI  - Sigma factor RpoN employs a dual transcriptional regulation for controlling
      twitching motility and biofilm formation in Lysobacter enzymogenes OH11.
AB  - Lysobacter is a Gram-negative genus comprising a group of environmental bacteria
      with abilities to produce abundant novel antibiotics, as well as adopting a
      unique type IV pilus (T4P)-mediated twitching motility (TM) that remains poorly
      understood. Here, we employ L. enzymogenes OH11 exhibiting significant antifungal
      activity as a working model to address this issue. Via mutating the 28 potential
      sigma factors in strain OH11, we have identified one protein RpoNOH11 (sigma 54)
      that is indispensable for T4P formation and TM. We further showed that RpoNOH11
      not only regulates the transcription of pilA, but also another crucial gene chpA
      that encodes a hybrid two-component transduction system. The L. enzymogenes
      RpoNOH11 was found to directly bind to the promoter of chpA to control its
      transcription, which is found to be essential for the T4P-mediated TM. To our
      knowledge, such a transcriptional regulation performed by RpoN in control of
      bacterial TM has never been reported. Finally, we showed that L. enzymogenes OH11
      could also produce biofilm that is likely employed by this strain to infect
      fungal pathogens. Mutation of rpoN OH11, pilA and chpA all led to a significant
      decrease in biofilm formation, suggesting that the dual transcriptional
      regulation of pilA and chpA by RpoNOH11 plays a key role for RpoNOH11 to modulate
      the biofilm formation in L. enzymogenes. Overall, this study identified chpA as a
      new target of RpoN for controlling the T4P-mediated twitching motility and
      biofilm formation in L. enzymogenes OH11.

PMID- 29067483
TI  - Natural history of the ossification of cervical posterior longitudinal ligament:
      a three dimensional analysis.
AB  - PURPOSE: Three-dimensional (3D) imaging using computed tomography (CT) has made
      it possible to accurately evaluate ossification of the posterior longitudinal
      ligament (OPLL). Recently, we developed a novel technique to measure ossification
      volume using the 3D analysis. The purpose of this study was to investigate the
      natural course of OPLL and the risk factors for volume progression. METHODS:
      Forty-one patients (22 males and 19 females) diagnosed with cervical OPLL who had
      been non-surgically treated were included in this study. We evaluated clinical
      examination, radiological findings, and the volume of ossified lesions during at
      least 1-year intervals. Furthermore, we performed risk factor analysis for OPLL
      volume progression. RESULTS: The mean ossification volume was 2047.4 +/- 1437.3
      mm3 in the first examination and 2201.0 +/- 1524.1 mm3 in the final examination,
      indicating a significant increase during the follow-up period (p < 0.001). The
      mean annual rate of lesion increase was 4.1 +/- 2.7%. Univariate regression
      analysis demonstrated significant relationships between the annual rate of lesion
      increase and age (beta = -0.48; p = 0.001), body weight (BW) (beta = 0.36; p =
      0.02), and body mass index (BMI) (beta = 0.35; p = 0.03). Furthermore, age was
      the only significant predictor of OPLL progression (R2 = 0.23; p = 0.001) in
      multivariate liner regression analysis. CONCLUSIONS: Younger age, higher BW, and
      higher BMI are predictors of OPLL progression. Younger age is the most
      significant predictor in non-surgically treated patients.

PMID- 29067484
TI  - Crystal structure and iterative saturation mutagenesis of ChKRED20 for expanded
      catalytic scope.
AB  - ChKRED20 is an efficient and robust anti-Prelog ketoreductase that can catalyze
      the reduction of ketones to chiral alcohols as pharmaceutical intermediates with
      great industrial potential. To overcome its limitation on the bioreduction of
      ortho-substituted acetophenone derivatives, the X-ray crystal structure of the
      apo-enzyme of ChKRED20 was determined at a resolution of 1.85 A and applied to
      the molecular modeling and reshaping of the catalytic cavity via three rounds of
      iterative saturation mutagenesis together with alanine scanning and
      recombination. The mutant Mut3B was achieved with expanded catalytic scope that
      covered all the nine substrates tested as compared with two substrates for the
      wild type. It exhibited 13-20-fold elevated k cat/K m values relative to the wild
      type or to the first gain-of-activity mutant, while retaining excellent
      stereoselectivity toward seven of the substrates (98-> 99% ee). Another mutant
      29G10 displayed complementary selectivity for eight of the ortho-substituted
      acetophenone derivatives, with six of them delivering excellent stereoselectivity
      (90-99% ee). Its k cat/K m value toward 1-(2-fluorophenyl)ethanone was 5.6-fold
      of the wild type. The application of Mut3B in elevated substrate concentrations
      of 50-100 g/l was demonstrated in 50-ml reactions, achieving 75-> 99% conversion
      and > 99% ee.

PMID- 29067481
TI  - Are some people at increased risk of paracetamol-induced liver injury? A critical
      review of the literature.
AB  - PURPOSE: Paracetamol is one of the world's most commonly used drugs. In overdose,
      it is well established to be hepatotoxic. The aim of this review was to identify
      factors that have been, or actually are, associated with the development of liver
      injury after paracetamol exposure in humans. METHOD: Google Scholar and PubMed
      were searched on various dates between December 2016 and March 2017. Papers
      identified had their references analysed for further studies that might be
      relevant. RESULTS: At the time of writing, there was little good quality clinical
      evidence-from studies of paracetamol overdose or therapeutic use-to suggest that
      any groups of people are relatively protected from, or are at greater risk of,
      liver injury. The factors that were historically used to indicate higher risk in
      the UK have no good quality clinical evidence to support their re-introduction
      into clinical practice. The safe (and still effective) oral dose of paracetamol
      in patients weighing less than 50 kg has not been established. CONCLUSION: There
      is no patient group that is unequivocally at elevated risk of paracetamol-induced
      liver toxicity. We propose two clinical scenarios that warrant further research.
      Firstly, there is a need to establish whether the dose of paracetamol should be
      reduced in patients with low body weight. Secondly, if or when genomic
      information regarding individual patients becomes readily available to inform
      prescribing, we propose the contribution of the genome to paracetamol toxicity
      should be re-investigated with robustly designed studies. Such studies could
      enhance the safe use of one of the most frequently taken drugs.

PMID- 29067485
TI  - The role of previous falls in major osteoporotic fracture prediction in
      conjunction with FRAX in older Chinese men and women: the Mr. OS and Ms. OS
      cohort study in Hong Kong.
AB  - : Falls are a major concern in terms of fracture risk. Although awareness rising
      for the absence of falls in the FRAX algorithm, our study only identified the
      independent predictive role of previous recurrent falls and their better
      conjunction use with FRAX for major osteoporotic fracture prediction in older
      Chinese men. INTRODUCTION: Although the association of falls with fracture has
      been widely explored, the impact of previous falls is not included in the FRAX
      algorithm currently. Our aim was to examine the FRAX-independent associations
      between falls in the previous year and subsequent fracture risk, as well as the
      conjunctive use of falls and the FRAX score for major osteoporotic fracture (MOF)
      prediction in older Chinese people. METHODS: Four thousand community older men
      and women aged 65 years or older were followed up for 9.9 +/- 2.7 and 8.8 +/- 1.5
      years, respectively. The associations between falls in the previous 1 year and
      MOF risk by follow-up years were evaluated using the Fine and Gray model. New
      prediction scores were calculated by incorporating the falls and FRAX scores
      using the Fine and Gray model, or developed by adjusting the FRAX scores by 30%
      increased risk for each fall in the previous year. The predictive powers for MOF
      risk between the new scores and FRAX scores were evaluated by the area under the
      curve (AUC) and category-based net reclassification improvement index (NRI).
      RESULTS: During the follow-up period, 139 (7.0%) men and 236 (11.8%) women had at
      least one incident MOF. One previous fall significantly predicted the first year
      incident MOF in men [hazard ratio (HR) (95%CI), 3.47 (1.02, 11.80)]. Previous
      recurrent falls significantly predicted a 10-year incident MOF in men [HR
      (95%CI), 2.42 (1.30, 4.51)]. In men, the fall-adjusting FRAX scores showed
      significant improvement on total net reclassification of fracture (3-6%). No
      improved predictive accuracy shown in women. CONCLUSION: Falls in the previous
      year are likely to provide some predictive power to FRAX for MOF risk assessment
      in older Chinese men, but not women.

PMID- 29067488
TI  - [The Historicity of Data: Concepts, Tools, and Practices During the Nineteenth
      Century].
AB  - This essay explores the use of the concept of "data" during the nineteenth
      century. It traces the development of manual data driven research decades before
      the introduction of Hollerith machines and electronic computers. Census
      statisticians in late-nineteenth century Prussia employed moveable paper tools to
      assemble numerical information in novel ways; their actions fundamentally recast
      processes of compilation. The paper considers the epistemic impact of moving data
      inscribed on tons of paper, reconstructing the logistics of a circulatory
      compilation system spread across the Prussian capital. The movement of data in
      Wilhelmine Berlin reached outward from the statistical bureau to encompass the
      homes of many women, enlisted in a minutely-orchestrated putting out system. The
      essay scrutinizes the social and intellectual requirements necessary to classify,
      sort, and aggregate the information on the loose paper slips fast and without
      error. For all of their inventiveness, Prussian statisticians were neither the
      first nor the only ones to gather, process and visualize data in imaginative
      ways. As this essay demonstrates, many so-called "Baconian" sciences developed
      similar tools and practices to those of Prussian statisticians. Making and moving
      data sparked historical sensitivity in disciplines well beyond population
      statistics, from taxonomy to paleontology, yielding unexpected revelations.

PMID- 29067486
TI  - Improving the clinical value and utility of CGM systems: issues and
      recommendations : A joint statement of the European Association for the Study of
      Diabetes and the American Diabetes Association Diabetes Technology Working Group.
AB  - The first systems for continuous glucose monitoring (CGM) became available over
      15 years ago. Many then believed CGM would revolutionise the use of intensive
      insulin therapy in diabetes; however, progress towards that vision has been
      gradual. Although increasing, the proportion of individuals using CGM rather than
      conventional systems for self-monitoring of blood glucose on a daily basis is
      still low in most parts of the world. Barriers to uptake include cost,
      measurement reliability (particularly with earlier-generation systems), human
      factors issues, lack of a standardised format for displaying results and
      uncertainty on how best to use CGM data to make therapeutic decisions. This
      scientific statement makes recommendations for systemic improvements in clinical
      use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is
      to improve safety and efficacy in order to support the advancement of the
      technology in achieving its potential to improve quality of life and health
      outcomes for more people with diabetes.

PMID- 29067489
TI  - Social vulnerability as a predictor of physical activity and screen time in
      European children.
AB  - OBJECTIVES: To examine associations between social vulnerabilities and meeting
      physical activity (PA) and screen time (ST) recommendations during a 2-year
      follow-up. METHODS: 13,891 children aged 2.0 to  < 9.9 from eight European
      countries were assessed at baseline and 8482 children at follow-up. Children's
      sports club membership, PA and ST were collected via parental questionnaires.
      Moderate-to-vigorous physical activity (MVPA) was objectively assessed with
      accelerometers. Performing at least 1 h of MVPA daily and spending less than 2 h
      of ST defined physically active and non-sedentary children, respectively.
      Vulnerable groups were defined at baseline as children whose parents had minimal
      social networks, from non-traditional families, with migrant origin or with
      unemployed parents. Logistic mixed-effects analyses were performed adjusting for
      classical socioeconomic indicators. RESULTS: Children whose parents had minimal
      social networks had a higher risk of non-compliance with PA recommendations
      (subjectively assessed) at baseline. Migrants and children with unemployed
      parents had longer ST. All vulnerable groups were less likely to be sports club
      members. CONCLUSIONS: Migrants and children with unemployed parents are at risk
      for excessive ST and all vulnerable groups have lower odds of being sports club
      members.

PMID- 29067490
TI  - Derivation of some contemporary scales to measure adolescent risk-taking in
      Canada.
AB  - OBJECTIVES: To derive a contemporary series of composite indicators of adolescent
      risk-taking, inspired by the US CDC Framework and Problem Behaviour Theory.
      METHODS: Factor analyses were performed on 28-risk behaviours in a nationally
      representative sample of 30,096 Grades 6-10 students from the 2014 Canadian
      Health Behaviour in School-aged Children study. RESULTS: Three composite
      indicators emerged from our analysis: (1) Overt Risk-Taking (i.e., substance use,
      caffeinated energy drink consumption, fighting, and risky sexual behaviour), (2)
      Aversion to a Healthy Lifestyle (i.e., physical inactivity and low fruit and
      vegetable consumption), and (3) Screen Time Syndrome (i.e., abnormally high
      screen time use combined with unhealthy snacking). These three composite
      indicators of risk-taking were observed consistently with strong psychometric
      properties across different grade groups (6-8, 9-10). CONCLUSIONS: The three
      composite indicators of adolescent risk-taking each draw from multiple domains
      within the CDC framework, and support a novel, empirically directed approach of
      conceptualizing multiple risk behaviours among adolescents. The measures also
      highlight the breadth and diversity of risk behaviour engagement among Canadian
      adolescents. Research and preventive interventions should simultaneously consider
      the related behaviours within each of these composite indicators.

PMID- 29067487
TI  - Epigenetic modifications of the Zfp/ZNF423 gene control murine adipogenic
      commitment and are dysregulated in human hypertrophic obesity.
AB  - AIMS/HYPOTHESIS: Subcutaneous adipocyte hypertrophy is associated with insulin
      resistance and increased risk of type 2 diabetes, and predicts its future
      development independent of obesity. In humans, subcutaneous adipose tissue
      hypertrophy is a consequence of impaired adipocyte precursor cell recruitment
      into the adipogenic pathway rather than a lack of precursor cells. The zinc
      finger transcription factor known as zinc finger protein (ZFP) 423 has been
      identified as a major determinant of pre-adipocyte commitment and maintained
      white adipose cell function. Although its levels do not change during
      adipogenesis, ectopic expression of Zfp423 in non-adipogenic murine cells is
      sufficient to activate expression of the gene encoding peroxisome proliferator
      activated receptor gamma (Ppargamma; also known as Pparg) and increase the
      adipogenic potential of these cells. We investigated whether the Zfp423 gene is
      under epigenetic regulation and whether this plays a role in the restricted
      adipogenesis associated with hypertrophic obesity. METHODS: Murine 3T3-L1 and NIH
      3T3 cells were used as fibroblasts committed and uncommitted to the adipocyte
      lineage, respectively. Human pre-adipocytes were isolated from the stromal
      vascular fraction of subcutaneous adipose tissue of 20 lean non-diabetic
      individuals with a wide adipose cell size range. mRNA levels were measured by
      quantitative real-time PCR, while methylation levels were analysed by bisulphite
      sequencing. Chromatin structure was analysed by micrococcal nuclease protection
      assay, and DNA-methyltransferases were chemically inhibited by 5-azacytidine.
      Adipocyte differentiation rate was evaluated by Oil Red O staining. RESULTS:
      Comparison of uncommitted (NIH-3T3) and committed (3T3-L1) adipose precursor
      cells revealed that Zfp423 expression increased (p < 0.01) in parallel with the
      ability of the cells to differentiate into mature adipocytes owing to both
      decreased promoter DNA methylation (p < 0.001) and nucleosome occupancy
      (nucleosome [NUC] 1 p < 0.01; NUC2 p < 0.001) in the 3T3-L1 compared with NIH-3T3
      cells. Interestingly, non-adipogenic epigenetic profiles can be reverted in NIH
      3T3 cells as 5-azacytidine treatment increased Zfp423 mRNA levels (p < 0.01),
      reduced DNA methylation at a specific CpG site (p < 0.01), decreased nucleosome
      occupancy (NUC1, NUC2: p < 0.001) and induced adipocyte differentiation (p <
      0.05). These epigenetic modifications can also be initiated in response to
      changes in the pre-adipose cell microenvironment, in which bone morphogenetic
      protein 4 (BMP4) plays a key role. We finally showed that, in human adipocyte
      precursor cells, impaired epigenetic regulation of zinc nuclear factor (ZNF)423
      (the human orthologue of murine Zfp423) was associated with inappropriate
      subcutaneous adipose cell hypertrophy. As in NIH-3T3 cells, the normal ZNF423
      epigenetic profile was rescued by 5-azacytidine exposure.
      CONCLUSIONS/INTERPRETATION: Our results show that epigenetic events regulate the
      ability of precursor cells to commit and differentiate into mature adipocytes by
      modulating ZNF423, and indicate that dysregulation of these mechanisms
      accompanies subcutaneous adipose tissue hypertrophy in humans.

PMID- 29067491
TI  - Impact of malondialdehyde-modified low-density lipoprotein on coronary plaque
      vulnerability in patients not receiving lipid-lowering therapy: a whole coronary
      analysis with multislice-computed tomography.
AB  - Vulnerable plaque disruption was suggested as a primary cause of acute coronary
      syndrome. This study investigated the impact of malondialdehyde-modified low
      density lipoprotein (MDA-LDL) on whole coronary plaque vulnerability, based on
      multislice-computed tomography (MSCT). We included 197 patients that were not
      receiving lipid-lowering therapy. We retrospectively analyzed MSCT and MDA-LDL
      measurements. We defined a CT-derived vulnerable plaque as a plaque with a
      remodeling index > 1.10 and a mean CT density value < 30 HU. Vulnerable plaques
      were detected in 60 patients (30%). Patients with vulnerable plaques had
      significantly higher MDA-LDL levels than patients without vulnerable plaques
      (151.3 +/- 42.3 vs. 118.5 +/- 41.7 U/L, p < 0.01). A univariate regression
      analysis showed that vulnerable plaques were significantly related to MDA-LDL
      levels [10 U/L groups, odds ratio (OR): 1.19; p < 0.01] and in a multivariate
      model (10 U/L groups, OR: 1.18; p < 0.01). Patients with multivessel vulnerable
      plaques had significantly higher MDA-LDL levels than those with single-vessel
      involvement or no vulnerable plaque (172.4 +/- 28.5 vs. 142.8 +/- 44.2 vs. 118.5
      +/- 41.7 U/L, respectively; p < 0.01). MDA-LDL difference was observed for all
      LDL tertiles (bottom; 128.9 +/- 41.1 vs. 97.3 +/- 25.0 U/L, p < 0.01, middle;
      142.6 +/- 42.7 vs. 122.5 +/- 35.1 U/L, p = 0.05, top; 166.0 +/- 38.1 vs. 143.5 +/
      51.6 U/L, p = 0.05). Increased MDA-LDL levels were associated with the presence
      and extent of vulnerable plaques, regardless of LDL levels.

PMID- 29067492
TI  - Thromboembolisms in atrial fibrillation and heart failure patients with a
      preserved ejection fraction (HFpEF) compared to those with a reduced ejection
      fraction (HFrEF).
AB  - Heart failure (HF) is classified into three clinical subtypes: HF with a
      preserved ejection fraction (HFpEF: EF >= 50%), HF with a mid-range ejection
      fraction (HFmrEF: 40 <= EF < 49%), and HF with a reduced ejection fraction
      (HFrEF: EF < 40%). These types often coexist with atrial fibrillation (AF). We
      investigated the rate of strokes/systemic embolisms (SSEs) in AF patients with
      HFpEF (AF-HFpEF) compared to that in those with HFrEF (AF-HFrEF: HFmrEF and
      HFrEF), and examined the independent predictors. We prospectively enrolled 1350
      patients admitted to our hospital for worsening HF. We identified 301 patients
      with either AF-HFpEF (n = 129, 43%) or AF-HFrEF (n = 172, 57%). Compared to the
      patients with AF-HFrEF, those with AF-HFpEF were older and more likely to be
      female. Oral anticoagulant use was 63 vs. 66%, respectively. During a mean follow
      up period of 26 months, 21 (7%) and 66 (22%) patients had SSEs and all-cause
      death, respectively. The crude annual rates of SSEs (3.9 vs. 2.7%, P = 0.47) were
      similar between the groups. In a multivariate Cox regression analysis, an age >=
      75 years (hazard ratio 2.14, 95% confidence interval 1.32-3.58, P < 0.01) and the
      plasma B-type natriuretic peptide (BNP) level >= 341 pg/ml (hazard ratio 1.60,
      95% confidence interval 1.07-2.39, P < 0.05) were associated with SSEs. The EF
      was not an independent predictor of SSEs (hazard ratio 1.01, 95% confidence
      interval 0.98-1.04, P = 0.51). There were no significant differences in the rates
      of SSEs between AF-HFpEF and AF-HFrEF. Patients with HF and concomitant AF should
      be treated with anticoagulants irrespective of EF.

PMID- 29067493
TI  - Sex-specific developmental models for Creophilus maxillosus (L.) (Coleoptera:
      Staphylinidae): searching for larger accuracy of insect age estimates.
AB  - Differences in size between males and females, called the sexual size dimorphism,
      are common in insects. These differences may be followed by differences in the
      duration of development. Accordingly, it is believed that insect sex may be used
      to increase the accuracy of insect age estimates in forensic entomology. Here,
      the sex-specific differences in the development of Creophilus maxillosus were
      studied at seven constant temperatures. We have also created separate
      developmental models for males and females of C. maxillosus and tested them in a
      validation study to answer a question whether sex-specific developmental models
      improve the accuracy of insect age estimates. Results demonstrate that males of
      C. maxillosus developed significantly longer than females. The sex-specific and
      general models for the total immature development had the same optimal
      temperature range and similar developmental threshold but different thermal
      constant K, which was the largest in the case of the male-specific model and the
      smallest in the case of the female-specific model. Despite these differences,
      validation study revealed just minimal and statistically insignificant
      differences in the accuracy of age estimates using sex-specific and general
      thermal summation models. This finding indicates that in spite of statistically
      significant differences in the duration of immature development between females
      and males of C. maxillosus, there is no increase in the accuracy of insect age
      estimates while using the sex-specific thermal summation models compared to the
      general model. Accordingly, this study does not support the use of sex-specific
      developmental data for the estimation of insect age in forensic entomology.

PMID- 29067494
TI  - Effects of water ionic composition on acid-base regulation in rainbow trout,
      during hypercarbia at rest and during sustained exercise.
AB  - Aquatic hypercarbia (elevated environmental CO2) results in a blood acidosis in
      fish, which is compensated by the exchange of Na+ and/or Cl- for its acid/base
      counterpart (H+, HCO3-) across the gill epithelium. To date, no studies exist on
      how a single species, capable of inhabiting both fresh and saltwater, responds to
      hypercarbia, at rest or during sustained exercise. Rainbow trout was acclimated
      to soft water (in mmol l- 1: Na+, 0.08; Cl-, 0.05; pH 6.7-6.8), hard water (in
      mmol l- 1: Na+, 2.4; Cl-, 0.2; pH 7.9-8.0), or 85% saltwater (28 ppt) (in mmol l-
      1: Na+, 410; Cl-, 476; pH 7.8-8.0). Acid-base relevant blood parameters were
      measured during a 1 kPa CO2 hypercarbia exposure, both at rest and during
      sustained exercise (~ 60% U crit). After 48 h of hypercarbia, resting hard-, and
      saltwater trout fully restored blood pH, whereas soft-water-acclimated trout was
      only 60.6 +/- 10.5% recovered. In all fish, recovery was associated with an
      increase in plasma [HCO3-] and an equimolar reduction in plasma [Cl-]. Following
      8 h of hypercarbia during sustained exercise, saltwater fish fully restored blood
      pH, while soft- and hard water fish were 42 +/- 18.1 and 64 +/- 6.8% recovered,
      respectively. Results provide intra-specific support demonstrating that saltwater
      acclimated fish acid-base compensate faster than freshwater fish during
      hypercarbia. Furthermore, data indicate that recovery during hypercarbia in trout
      is more rapid during exercise than rest. This not only demonstrates an important
      link between ambient water ion levels and ability to recover from acid-base
      disturbances, but also it presents novel data, suggesting that exercise may
      enhance acid-base regulation.

PMID- 29067497
TI  - [Counterfeit medicines].

PMID- 29067495
TI  - Short-term application of tocilizumab during myocardial infarction (STAT-MI).
AB  - Acute myocardial infarction (MI) occurs when blood supply falls below critical
      levels and normal cellular maintenance mechanisms fail. Interleukin-6 (IL-6) is a
      proinflammatory cytokine released in MI and associated with poor clinical
      outcomes. Tocilizumab (TCZ) is a humanized monoclonal antibody against the IL-6
      receptor. In a randomized, double-blinded, placebo controlled trial we assigned
      subjects admitted with MI a single TCZ dose of 162 mg subcutaneously vs. placebo
      in addition to standard of care medications and interventions. Primary outcome
      was a change in major adverse cardiac events (MACE) 30 days after enrollment.
      Secondary outcomes assessed changes in CRP 30 days after enrollment, changes in
      QT/QTc, and monitoring for trends in adverse events. Futility analysis was
      performed as subject enrollment slowed and no trends were noted in either the
      primary or secondary outcomes. Twenty-eight subjects were enrolled; 12 to TCZ and
      16 to placebo. No statistically significant differences were noted between study
      arms regarding demographics, comorbidities, or medical/interventional therapies
      received. No statistically significant differences in MACE were observed. CRP
      increased after administration of TCZ but this was not statistically significant.
      No adverse events or safety signals were observed. Though futility analysis
      suggested that the primary outcome was not likely achievable as our recruitment
      slowed, we did not observe any adverse events or safety trends. Building on this
      information, future studies should be conducted to assess a true benefit from TCZ
      as adjunct therapy for MI. The work reported herein was performed under United
      States Air Force Surgeon General approved Clinical Investigation FKE20140029 and
      has been registered at ClinicalTrials.gov under identifier NCT02419937.

PMID- 29067496
TI  - A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated
      regression of established solid tumors in mice.
AB  - Strong evidence exists supporting the important role T cells play in the immune
      response against tumors. Still, the ability to initiate tumor-specific immune
      responses remains a challenge. Recent clinical trials suggest that bispecific
      antibody-mediated retargeted T cells are a promising therapeutic approach to
      eliminate hematopoietic tumors. However, this approach has not been validated in
      solid tumors. PF-06671008 is a dual-affinity retargeting (DART(r))-bispecific
      protein engineered with enhanced pharmacokinetic properties to extend in vivo
      half-life, and designed to engage and activate endogenous polyclonal T cell
      populations via the CD3 complex in the presence of solid tumors expressing P
      cadherin. This bispecific molecule elicited potent P-cadherin expression
      dependent cytotoxic T cell activity across a range of tumor indications in vitro,
      and in vivo in tumor-bearing mice. Regression of established tumors in vivo was
      observed in both cell line and patient-derived xenograft models engrafted with
      circulating human T lymphocytes. Measurement of in vivo pharmacodynamic markers
      demonstrates PF-06671008-mediated T cell activation, infiltration and killing as
      the mechanism of tumor inhibition.

PMID- 29067498
TI  - [Potentials in the regionalization of health indicators using small-area
      estimation methods : Exemplary results based on the 2009, 2010 and 2012 GEDA
      studies].
AB  - Nationwide health surveys can be used to estimate regional differences in health.
      Using traditional estimation techniques, the spatial depth for these estimates is
      limited due to the constrained sample size. So far - without special refreshment
      samples - results have only been available for larger populated federal states of
      Germany. An alternative is regression-based small-area estimation techniques.
      These models can generate smaller-scale data, but are also subject to greater
      statistical uncertainties because of the model assumptions. In the present
      article, exemplary regionalized results based on the studies "Gesundheit in
      Deutschland aktuell" (GEDA studies) 2009, 2010 and 2012, are compared to the self
      rated health status of the respondents. The aim of the article is to analyze the
      range of regional estimates in order to assess the usefulness of the techniques
      for health reporting more adequately. The results show that the estimated
      prevalence is relatively stable when using different samples. Important
      determinants of the variation of the estimates are the achieved sample size on
      the district level and the type of the district (cities vs. rural regions).
      Overall, the present study shows that small-area modeling of prevalence is
      associated with additional uncertainties compared to conventional estimates,
      which should be taken into account when interpreting the corresponding findings.

PMID- 29067499
TI  - Prognosis of surgical treatment of the tethered cord syndrome in children.
AB  - PURPOSE: The aim of this study was to identify the factors relevant to the
      prognosis of the outcome of the surgical treatment of the tethered cord syndrome
      (TCS). METHODS: The results of surgical treatment performed on 58 children with
      TCS were analyzed, with follow-up periods ranging from 6 months to 5 years. The
      data of preoperative clinical and instrumental examinations, as well as those of
      intraoperative electrophysiological diagnostics and morphometry, were compared
      with the dynamics of the TCS clinical presentation. RESULTS: The recovery rate
      was significantly higher in children with filum terminale abnormality (p =
      0.014), as well as grade I tethering (p = 0.0037), and when the spinal cord
      tracts at the level of intervention were intact (p = 0.018). Complete untethering
      (p = 0.04) and a low threshold value of amperage in direct stimulation (< 1 mA)
      (p = 0.016) were identified as factors for a favorable outcome. Worsening of
      neurological symptoms was more frequent in children operated over the age of 10
      (p = 0.03), when the TCS was manifested exclusively through the pelvic
      dysfunction (p = 0.00004), if the F-wave block is less than 30% (p = 0.0045) and
      the stimulation threshold during root mapping ranged from 1 to 5 mA (p = 0.01).
      CONCLUSION: The operation is recommended when structural changes are minimal. In
      case of severe structural changes, if the spinal cord tracts are intact, the
      indications for operation are determined by the risk of irreversible structural
      changes due to the natural course of the disease, although the risks are
      substantially higher.

PMID- 29067500
TI  - DTI fusion with conventional MR imaging in intra-operative MRI suite for
      paediatric brainstem glioma biopsy.

PMID- 29067501
TI  - Monitoring intraventricular vancomycin for ventriculostomy access device
      infection in preterm infants.
AB  - PURPOSE: Ventriculitis is a known complication during external CSF drainage in
      preterm infants with posthaemorrhagic ventricular dilatation. Staphylococci are
      most frequently isolated in device-associated ventriculitis, and hence,
      intraventricular vancomycin is a commonly used therapy. Our aim was to study the
      CSF vancomycin level pattern and drug safety in ventriculostomy access device
      infection in preterm infants less than 28 weeks gestation. METHODS: This single
      centre, retrospective case series included seven infants with a median
      gestational age of 25 + 4 weeks (range 23 + 6 to 27 + 5 weeks). Ventriculitis was
      defined as elevated CSF white cell count of > 20/mm3 or positive CSF culture. The
      CSF vancomycin concentrations following intraventricular vancomycin
      administration were studied. RESULTS: Forty treatment episodes of
      intraventricular vancomycin administration were studied in seven preterm infants.
      Maximum CSF vancomycin concentrations were 24.9 mg/L (3 mg, n = 8, observed
      concentration-time (OCT), hours (h) = 19), 96.3 mg/L (5 mg, n = 17, OCT(h) = 14),
      94 mg/L (10 mg, n = 14, OCT(h) = 24), and 230.7 mg/L (15 mg, n = 1, OCT(h) = 24).
      The threshold for re-dosage is set at CSF vancomycin level of < 10 mg/L. In all
      patients, ventriculitis resolution (defined as sterile CSF and CSF WCC of <
      20/mm3) was achieved in a median of 5.5 days (range 2-31 days). Individual
      microbiology data is provided in the online resource. CONCLUSION:
      Intraventricular vancomycin is an effective treatment for ventriculostomy access
      device infection in preterm infants. In doses ranging from 3 to 15 mg, sufficient
      CSF vancomycin level is generated to achieve microbiological cure without any
      reported adverse effects. Daily CSF drug monitoring is recommended to define
      dosage interval to maintain drug concentration above breakpoint of minimum
      inhibitory concentration.

PMID- 29067502
TI  - A multidisciplinary approach for the treatment of young patients with suprasellar
      osteochondroma.
AB  - BACKGROUND: Osteochondroma is the most common benign bone tumor; intracranial
      osteochondroma is a very rare finding in the neurosurgical literature and most of
      them arise from the skull base. CASE REPORT: We report a case of suprasellar
      ostheocondroma in a 16-year-old female, with its CT and MRI appearances, which
      caused visual deficits, resolved after surgery. DISCUSSION: To our knowledge,
      this is the fifth case of osteochondroma affecting the suprasellar region that
      has been reported, with all the characteristic features of this tumor: optic
      chiasmal syndrome, intralesional calcifications, cartilage cap, and contrast
      enhancement. CONCLUSION: Multidiscplinary teams, including a neuro
      ophthalmologist, endocrinologist, neuroradiologist, neurosurgeon, and
      neuropathologist are needed for correct treatment of the disease and appropriate
      follow-up.

PMID- 29067503
TI  - Clinical features, radiologic findings, and treatment of pediatric germ cell
      tumors involving the basal ganglia and thalamus: a retrospective series of 15
      cases at a single center.
AB  - PURPOSE: Pediatric germ cell tumors (GCTs) involving the basal ganglia and
      thalamus are relatively rare neoplasms which have not been extensively described.
      We here summarize the clinical and radiological features of a series of such
      tumors and discuss optimal treatment strategies based upon our experience.
      METHODS: A total of 15 pediatric patients with basal ganglionic and thalamic GCTs
      were treated between 2011 and 2016 at West China Hospital. Epidemiological
      characteristics, clinical features, imaging findings, and treatment strategies
      were reviewed retrospectively. RESULTS: GCTs constituted 28% (15/53) of pediatric
      basal ganglionic and thalamic tumors in our institution between 2011 and 2016.
      There were 12 males and 3 females with mean age of 11.7 +/- 2.8 years (range, 7
      16 years). The most common initial manifestation was hemiparesis (n = 13, 86.7%),
      followed by headache (n = 5, 33.3%), vomiting (n = 3, 20.0%), cognitive
      disturbance (n = 2, 13.3%), and seizure (n = 1, 6.7%). No tumors were
      incidentally detected. The mean duration of the symptoms before diagnosis was 4.4
      +/- 3.9 months (range from 9 days to 13 months). The maximum diameters of the
      lesions ranged from 3.2 to 6.5 cm (mean 4.7 +/- 1.1 cm). Cysts were seen in
      tumors in MRIs in 11 patients (73%), intratumoral hemorrhages in 3 (20%),
      calcification in 2 (13%), and there was obstructive hydrocephalus in 1 (7%). Of
      note, hemiatrophy was observed in 9 cases (60.0%). The mean follow-up for the 15
      patients was 28 months (range, 9-54 months), and no patients were lost. During
      the follow-up period, all patients (9 cases) with germinomas responded well to
      radiotherapy, and no recurrence was observed. Among 4 patients with mixed
      nongerminomatous germ cell tumor, 2 suffered tumor recurrence after treatment.
      Neurological deficits improved or remained unchanged in 12 patients but 3
      developed new dysfunction including significant cognitive disturbance and
      hemiparesis. CONCLUSIONS: Pediatric GCTs in the basal ganglia and thalamus are
      not as rare as previously considered. Tumor markers should be tested routinely
      for tumors in these sites in young patients. Optimal treatment strategy based on
      accurate diagnosis and comprehensive clinical assessment should be recommended.

PMID- 29067505
TI  - Length of synostosis and segmented intracranial volume correlate with age in
      patients with non-syndromic sagittal synostosis.
AB  - PURPOSE: The aim of this study is to compare the length of synostosis and
      segmented intracranial volume (SIV) with age in children with non-syndromic
      sagittal synostosis. METHODS: Thirty-three consecutive patients (22 boys) who had
      been operated by cranial vault remodeling because of sagittal synostosis were
      compared retrospectively from 3D-CT imaging data sets obtained from volumetric
      CT. The mean age of the patients at preoperative CT imaging was 0.49 (range 0.13
      1.3) years and at 1-year postoperative imaging 1.8 (range 1.3-3) years. The mean
      interval between preoperative CT imaging and surgery was 0.25 (range 0-0.8)
      years. Pearson's correlation and Student's t test were used in the statistical
      analyses. RESULTS: Length of sagittal synostosis correlated positively with age
      at preoperative CT (r = 0.688, p < 0.01). Children with total synostosis (n = 9)
      were significantly older (mean age 0.74 vs. 0.4 years, p < 0.01) than those with
      partial synostosis. Of partial synostoses, 9 were located anteriorly, 3 in the
      middle, and 12 posteriorly. The mean synostosis ratio (synostosis length/total
      sagittal suture length * 100) was 83%. Preoperative SIV correlated positively
      with age at preoperative CT (r = 0.788, p < 0.01), whereas the 1-year
      postoperative SIV did not correlate with age at operation. The older the child at
      the time of the operation, the less the percentage SIV increased. CONCLUSIONS:
      Length of sagittal synostosis and SIV increased with age.

PMID- 29067506
TI  - A unique case of lissencephaly with Crouzon syndrome heterozygous for FGFR2
      mutation.

PMID- 29067504
TI  - Multimaterial 3D printing preoperative planning for frontoethmoidal
      meningoencephalocele surgery.
AB  - INTRODUCTION: Surgical correction of frontoethmoidal meningoencephalocele,
      although rare, is still challenging to neurosurgeons and plastic reconstructive
      surgeons. It is fundamental to establish reliable and safe surgical techniques.
      The twenty-first century has brought great advances in medical technology, and
      the 3D models can mimic the correct tridimensional anatomical relation of a
      tissue organ or body part. They allow both tactile and spatial understanding of
      the lesion and organ involved. The 3D printing technology allows the preparation
      for specific surgery ahead of time, planning the surgical approach and developing
      plans to deal with uncommon and high-risk intraoperative scenarios. CASE
      PRESENTATION: The present report describes a case of frontoethmoidal
      encephalocele, (nasofrontal subtype) of a 19-month-old girl, whose surgical
      correction was planned using 3D printing modeling. CONCLUSION: The 3D model
      allowed a detailed discussion of the aspects of the surgical approach by having
      tissues of different consistencies and resistances, and also predicting with
      millimetric precision the bilateral orbitotomy measurements. Moreover, it was a
      fundamental and valuable factor in the multidisciplinary preoperative discussion.
      This approach allowed reducing the time of surgery, accurately planning the
      location of the osteotomies and precontouring the osteosynthesis material. 3D
      models can be very helpful tools in planning complex craniofacial operative
      procedures.

PMID- 29067507
TI  - Non-surgical transient cerebellar mutism-case report and systematic review.
AB  - INTRODUCTION: Transient cerebellar mutism has been well recognized in literature
      as a complication of posterior fossa tumor resection. It is marked by profound
      impairment of fluency, articulation, and modulation of speech, irritability and
      autistic features and typically resolves within days to months. Underlying
      pathophysiology is debated, but currently unknown. METHODS: We present a case of
      a child with similar clinical findings after cerebellitis, demonstration of
      diffuse cerebellar signal changes, swelling, and protruding tonsils at the level
      of foramen magnum. DISCUSSION: To support the hypothesis that this clinical
      syndrome may occur in a non-surgical context, we present a review of literature
      of non-surgical transient cerebellar mutism.

PMID- 29067508
TI  - Correction to: Dynamics of Total Microcystin LR Concentration in Three
      Subtropical Hydroelectric Generation Reservoirs in Uruguay, South America.
AB  - The original version of this article contains mistakes. The author inadvertently
      mentioned units mg/L in all the places of first paragraph under "Results and
      discussion" section. The correct unit is ug/L. In second paragraph, 10th line
      under "Results and discussion" section, the value should read as (< 0.05-85.4
      ug/mm3) instead of (< 0.05-854.00 ug/mm3). The units and value are corrected
      through this erratum.

PMID- 29067509
TI  - Transvenous Retrograde Thoracic Ductography: Initial Experience with 13
      Consecutive Cases.
AB  - PURPOSE: To report the feasibility and findings of transvenous retrograde
      thoracic duct cannulation. MATERIALS AND METHODS: The subjects were 13 patients
      who had undergone retrograde transvenous thoracic ductography. Despite
      conservative treatment, all required drainage for chylothorax, chylous ascites,
      or a chylous pericardial effusion. Lymphangiography was performed, and the
      junction of the thoracic duct with the vein was identified. A microcatheter was
      inserted into the thoracic duct retrogradely via the junction with the vein.
      RESULTS: The catheter could be inserted to the cervical part, thoracic part, and
      cisterna chyli in 12 (92.3%), nine (69.2%), and six (46.2%) patients,
      respectively. Successful transvenous thoracic ductography was performed in eight
      patients (61.5%). The cervical part of the thoracic duct was branched into a
      plexiform configuration beyond which the microcatheter could not be advanced to
      reach the thoracic part in three unsuccessful cases. The success rate of
      transvenous thoracic ductography was significantly higher with the simple type
      (80%) than with the plexiform type (0%; p = 0.035). No extravasation of contrast
      agent was seen in the eight patients with successful thoracic ductography.
      Thoracic duct embolization was performed in one patient with a chylous
      pericardial effusion in whom myriad lymph ducts connecting to the hilar and
      pericardial regions from the thoracic duct were found, and drainage was
      unnecessary. CONCLUSION: Transvenous retrograde thoracic ductography was
      successful in only eight of 13 patients (61.5%), but when the cervical part was
      the simple type, it was successful in eight of 10 patients (80%).

PMID- 29067511
TI  - Safety and Efficacy of Transarterial Radioembolization Combined with
      Chemoembolization for Bilobar Hepatocellular Carcinoma: A Single-Center
      Retrospective Study.
AB  - BACKGROUND: Radioembolization induced liver disease (REILD) is a possible sequela
      of transarterial radioembolization (TARE), particularly in cases of whole-liver
      treatment. To mitigate this problem, the safety and efficacy of combined
      transarterial chemoembolization (TACE) and TARE were evaluated for patients with
      bilobar hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Nineteen patients
      (mean age 60 years; range 27-82 years) treated for HCC between June 2012 and
      September 2014 were included in the analysis. Each patient was treated with
      combined TARE and TACE for bilobar HCC, with or without portal vein thrombosis.
      The hepatic lobe with large HCC was treated with TARE, and the other lobe with
      small HCC(s) was treated with TACE. Laboratory and clinical data were
      investigated to determine REILD occurrence. Survival data were analyzed to
      compare the treatment efficacy of alternative treatment modalities, including
      TACE and sequential TARE. RESULTS: All patients underwent TARE for a dominant
      tumor in one lobe and TACE for small nodule(s) in the other lobe of the liver.
      The mean yttrium-90 microspheres used in TARE were 2.8 GBq (range; 1.0-3.5 GBq),
      and the mean doses of doxorubicin and iodized oil were 24.5 mg and 5.2 mL,
      respectively, for TACE. No statistical differences were noted between laboratory
      data measured before and after treatment, and no procedure-related major clinical
      complications occurred. The median time-to-progression of patients was 10.0
      months, and the median overall survival was 27.3 months. CONCLUSION: Combined
      radioembolization and chemoembolization appears to be a safe and effective
      treatment modality for bilobar HCC.

PMID- 29067510
TI  - CT-Guided Percutaneous Sclerotherapy for Low-Flow Retrobulbar Intraconal Venous
      Malformations.
AB  - BACKGROUND AND AIMS: Until now, no study has focused exclusively on low-flow
      retrobulbar intraconal venous malformations (RIVMs) which may require treatment
      due to cosmetic defect, pain, and visual dysfunction. The treatment for RIVMs
      which surround the optic nerve remains challenging. This case series aimed to
      evaluate the technical feasibility, effectiveness, and safety of percutaneous
      sclerotherapy with polidocanol for low-flow RIVMs, using local anesthesia.
      METHOD: This is a prospective, non-comparative, single-center, interventional
      case series. All patients signed informed consent forms. Seven patients with
      RIVMs were treated with percutaneous sclerotherapy with polidocanol/air foam
      using CT guidance. Primary endpoints are reduction in the volume of RIVMs and
      pain relief assessed by visual analog scale (VAS). Secondary endpoints are
      exophthalmos and recording adverse events obtained in clinical follow-up during
      outpatient visits. RESULTS: Results revealed that the mean volume of RIVMs was
      decreased from 12.05 +/- 6.35 cm3 preoperatively to 1.56 +/- 0.43 cm3
      postoperatively, (p = 0.005), with a mean decrease of 87.05%. The intraocular
      pressure was decreased from 14.19 +/- 2.99 to 11.79 +/- 1.25 mmHg, (p = 0.043).
      The mean VAS score was decreased from 3.43 +/- 2.37 preoperatively to 1.29 +/-
      0.76 postoperatively, (p = 0.023). The exophthalmos score was decreased from 1.75
      +/- 0.27 to 1.34 +/- 0.31 cm, (p = 0.005). All patients were satisfied with the
      treatment, which did not leave a postoperative scar. CONCLUSIONS: The results of
      percutaneous intralesion injection of polidocanol for RIVMs are encouraging. The
      present results suggest that this method could be a safe and effective treatment
      option for patients with RIVMs.

PMID- 29067512
TI  - Bronchial Artery Embolization with Large Sized (700-900 um) Tris-acryl
      Microspheres (Embosphere) for Massive Hemoptysis: Long-Term Results (Clinical
      Research).
AB  - PURPOSE: To investigate the safety, efficacy and long-term results of bronchial
      artery embolization with microsphere particles (Embosphere(r) Microspheres,
      BioSphere Medical, Rockland, MA) 700-900 um in size for massive hemoptysis.
      METHODS: One hundred and seventy-four patients (94 female, 80 male; mean age 39.4
      +/- 5.7) who had bronchial artery embolization for massive hemoptysis between
      January 2010 and October 2015 were incorporated in the study. Patients had
      hemoptysis with a mean volume of 525 +/- 150 mL (median 500 mL, range 300-1200
      mL) over a 24-h period. Underlying pathologies included bronchial artery
      hypertrophy due to bronchiectasis (56.3% [98/174]), lung cancer (29.9% [52/174]),
      tuberculosis (10.3% [18/174]) and the rest remained idiopathic (3.4% [6/174]).
      Mean bronchial artery diameter before the intervention was 3.8 +/- 1.5 mm (median
      4 mm, range 3.1-7.5 mm). Median follow-up period was 56 months (range 10-82
      months). Primary objectives were the technical and clinical success. RESULTS:
      Technical success was 100%. Clinical success for preventing massive hemoptysis
      was 91.9% (160/174). There was no procedure-related mortality or morbidities.
      Minor complications such as chest pain were observed in nine patients (5.0%).
      Recurrent hemoptysis (8.1%) was observed within 6 months in 14 patients, ten of
      whom were treated with a second embolization session and the remaining four with
      a total of three embolization sessions. CONCLUSION: Bronchial artery embolization
      for massive hemoptysis with Embosphere particles 700-900 um in size is a safe and
      effective method with high technical and clinical success rates. Long-term
      results are excellent.

PMID- 29067513
TI  - Does antenatal steroids treatment prior to elective cesarean section at 34-37
      weeks of gestation reduce neonatal morbidity? Evidence from a case control study.
AB  - OBJECTIVE: To determine whether antenatal corticosteroids administration prior to
      an elective cesarean section (ECS) at 34-37 weeks gestation is associated with
      improved neonatal outcome. MATERIALS AND METHODS: A case control study of women
      with singleton pregnancies who underwent ECS between 34 and 37 weeks of gestation
      including two groups: (1) study group in which patients were treated with
      betamethasone prior to ECS (n = 58) and (2) control group matched for gestational
      age at delivery in which patients did not receive betamethasone (n = 107).
      Neonatal measures including respiratory distress syndrome (RDS), transient
      tachypnea of the newborn (TTN), oxygen requirement, admission to the special care
      unit, hypoglycemia, hyperbilirubinemia and length of hospitalization were
      determined in both groups. Composite respiratory morbidity was defined as the
      presence of either RDS, TTN, mechanical ventilation or oxygen requirement.
      RESULTS: There was no significant difference in the rate of composite respiratory
      morbidity nor its components between patients with and without betamethasone
      treatment (25.9 vs. 25.2%, respectively, p = 0.9). CONCLUSION: Antenatal
      treatment with corticosteroids prior to ECS at 34-37 weeks of gestation did not
      result in significant reduction in neonatal respiratory morbidity in our cohort
      of patients.

PMID- 29067514
TI  - Effects of genistein on pentylenetetrazole-induced behavioral and neurochemical
      deficits in ovariectomized rats.
AB  - Estrogenic compounds have been documented in literature to exert neuroprotective
      effects. This study investigated the potential neuroprotective effect of
      genistein; a phytoestrogen at doses of 5, 10, 20, and 40 mg/kg p.o. in
      ovariectomized rats challenged with pentylenetetrazole (PTZ) 90 mg/kg i.p.
      Systemic acute administration of PTZ induced seizures, increased oxidative
      stress, and caused apoptosis and histological abnormalities. Pretreatment with
      genistein delayed seizure onset, reduced the seizure duration, improved oxidative
      stress profile, decreased estrogen receptor expression, reduced apoptosis, and
      improved the histopathological pattern. Overall, the genistein doses (10 and 20
      mg/kg) showed the strongest protective effects. In conclusion, the current study
      suggests that genistein exhibits neuroprotective effects against PTZ-induced
      seizures. Such effects might be attributed to its estrogenic, antioxidant, and/or
      anti-apoptotic properties.

PMID- 29067515
TI  - "The Longest Way Round Is The Shortest Way Home": An Overhaul of Surgical Ward
      Rounds.
AB  - BACKGROUND: Ward rounds, a keystone of hospital surgical practice, have recently
      been under the spotlight. Poor-quality ward rounds can lead to a greater number
      of adverse events, thereby cascading to an increased financial strain on our
      already burdened healthcare systems. Faced with mounting pressures from both
      outside and inside health organizations, concerted efforts are required to
      restore it back into prominence where it can no longer take a backseat to the
      other duties of a surgeon. METHODS: The nucleus of this narrative review is
      derived from an extensive literature search on surgical ward rounds. RESULTS: In
      this review, we focus on the need for reforms, current characteristics of
      surgical ward rounds, obstacles encountered by competing interests and proposed
      solutions in delivery of effective ward rounds that can meet with newly laid
      guidelines. CONCLUSION: Ward rounds should be standardized and prioritized to
      improve patient care.

PMID- 29067518
TI  - Advancing Global Surgery: Moving Beyond Identifying Problems to Finding
      Solutions.

PMID- 29067516
TI  - Case-Control Study of Papillary Thyroid Carcinoma on Urinary and Dietary Iodine
      Status in South Korea.
AB  - BACKGROUND: The association between iodine levels and the risk of papillary
      thyroid cancer (PTC) has been suggested, but not definitively established. This
      study is to compare the iodine status of a group of patients with PTC (with and
      without BRAF V600E) with that of a healthy population cohort. METHODS: A cohort
      of patients scheduled for thyroidectomy was enrolled, along with a community
      based health-screening cohort with no known history of thyroid disease. Median
      urinary iodine (UI) levels, creatinine-adjusted median UI levels, and food
      frequency questionnaire (FFQ) scores (mean +/- SD) were compared. In a subgroup
      analysis, these values were compared between BRAF V600E-positive and BRAF V600E
      negative patients in the PTC group. RESULTS: The PTC group consisted of 210
      patients, and the control group consisted of 90 healthy individuals. Among the
      191 PTC patients whose BRAF V600E mutational status was reported, 169 (88.5%)
      were revealed positive for the mutation. The median UI levels were significantly
      higher in the PTC group (786.0 MUg/l) than the control group (112.0 MUg/l; p <
      0.001), as was the case with creatinine-adjusted median UI levels (884.6 MUg/g
      creatinine versus 182.0 MUg/g creatinine; p < 0.001) and FFQ scores (66.2 +/-
      17.5, range 13-114 versus 54.6 +/- 21.5, range 16-134; p < 0.001). No significant
      differences were seen in the subgroup analysis between BRAF V600E-positive and
      BRAF V600E-negative patients. CONCLUSIONS: Our results indicate that iodine
      status differs significantly between patients with PTC and healthy controls,
      suggesting that iodine may be involved in the occurrence of PTC, although the
      association between iodine levels and BRAF mutational status did not reach
      statistical significance.

PMID- 29067517
TI  - The Physician Attrition Crisis: A Cross-Sectional Survey of the Risk Factors for
      Reduced Job Satisfaction Among US Surgeons.
AB  - INTRODUCTION: A physician shortage is on the horizon, and surgeons are
      particularly vulnerable due to attrition. Reduced job satisfaction leads to
      increased job turnover and earlier retirement. The purpose of this study is to
      delineate the risk factors that contribute to reduced job satisfaction. METHODS:
      A cross-sectional survey of US surgeons was conducted from September 2016 to May
      2017. Screening for job satisfaction was performed using the abridged Job in
      General scale. Respondents were grouped into more and less satisfied using the
      median split. Twenty-five potential risk factors were examined that included
      demographic, occupational, psychological, wellness, and work-environment
      variables. RESULTS: Overall, 993 respondents were grouped into more satisfied (n
      = 502) and less satisfied (n = 491) cohorts. Of the demographic variables, female
      gender and younger age were associated with decreased job satisfaction (p = 0.003
      and p = 0.008). Most occupational variables (specialty, experience, academics,
      practice size, payment model) were not significant. However, increased average
      hours worked correlated with less satisfaction (p = 0.008). Posttraumatic stress
      disorder, burnout, wellness, all eight work-environment variables, and
      unhappiness with career choice were linked to reduced job satisfaction (p =
      0.001). CONCLUSION: A surgeon shortage has serious implications for health care.
      Job satisfaction is associated with physician retention. Our results suggest
      women and younger surgeons may be at increased risk for job dissatisfaction.
      Targeted work-environment interventions to reduce work-hours, improve hospital
      culture, and provide adequate financial reimbursement may promote job
      satisfaction and wellness.

PMID- 29067519
TI  - Reversible amygdala enlargement: a longitudinal observation of a patient with
      elderly onset temporal lobe epilepsy.

PMID- 29067520
TI  - How preschoolers and adults represent their joint action partner's behavior.
AB  - We investigated the cognitive mechanisms underlying turn-taking joint action in
      42-month-old children (Experiment 1) and adults (Experiment 2) using a behavioral
      task of dressing a virtual bear together. We aimed to investigate how
      participants represent a partners' behavior, i.e., in terms of specific action
      kinematics or of action effects. The bear was dressed by pressing a smaller and a
      bigger button. In the Action-response task, instructions asked participants to
      respond to the partner by pressing the same or opposite button; in the Action
      effect task they had to respond to the partner's action effect by dressing the
      bear with the lacking part of the clothing, which in some cases implied pressing
      the same button and in other cases implied pressing the opposite button. In 50%
      of the trials, the partner's association between each button and the ensuing
      effect (dressing the bear with t-shirt or pants) was reversed, while it never
      changed for participants. Both children and adults showed no effect of physical
      congruency of actions, but showed impaired performance in the Action-effect task
      if their partner achieved her effect through a different action-effect
      association than their own. These results suggest that, when encoding their
      partner's actions, agents are influenced by action-effect associations that they
      learnt through their own experience. While interference led to overt errors in
      children, it caused longer reaction times in adults, suggesting that a flexible
      cognitive control (that is still in development in young children) is required to
      take on the partner's perspective.

PMID- 29067521
TI  - Dental implant surfaces after insertion in bone: an in vitro study in four
      commercial implant systems.
AB  - OBJECTIVES: Primary healing of dental implants is influenced by their surface
      morphology. However, little is known about any alterations in morphology during
      their insertion. Therefore, the aim of this study was to evaluate the surface
      morphology of four different implant systems, following their insertion in
      porcine jaw bones. METHODS: Four fresh porcine mandible specimens were used. Six
      new implants of four systems (Ankylos(r) 4.5 * 14 mm, Frialit Synchro(r) 4.5 * 15
      mm, NobelReplace (r) Tapered Groovy RP 4.3 * 13 mm, Straumann SLA(r) Bone Level
      3.3 * 14 mm) were inserted, whereas one implant of each system served as a
      control. After their removal, implants were cleaned in an ultrasonic bath. All 28
      implants were examined quantitatively by 3D confocal microscopy for surface
      characteristics. RESULTS: In the evaluated zones, implants of the Ankylos,
      Frialit, and Straumann systems showed mostly a reduction of the mean surface
      roughness Sa, the maximal surface roughness Sz, and the developed surface area
      ratio Sdr; Nobel implants showed an increase in these parameters. With respect to
      all three parameters Sa, Sz, and Sdr, statistical analysis revealed that
      differences between the four systems were highly significant in the apical region
      of implants. Controls showed no morphologic alterations. CONCLUSION: The
      insertion process had an impact on the surface of all four implant systems.
      Anodized implant surface modification seems to result in more alterations
      compared with subtractive surface modifications. Therefore, surgical planning
      should take into consideration the choice of surface treatment because the
      characteristics of the implants may be modified during the installation process.
      CLINICAL RELEVANCE: The given information is of value for daily implantation
      practice and the course of osseointegration.

PMID- 29067522
TI  - Dopaminergic pathways for bruxism: a way forward?

PMID- 29067523
TI  - A reflection and analysis about the tools in the assessment of bruxism.

PMID- 29067525
TI  - Hypernatremia and acute pancreatitis in chronic kidney disease: back to the salt
      mines. Questions.
AB  - BACKGROUND: Acute pancreatitis can be a life-threatening complication in patients
      with chronic kidney disease (CKD), especially in kidney transplant recipients.
      CASE DIAGNOSIS/TREATMENT: The patient was 7 years old when he received renal
      transplantation for CKD secondary to posterior urethral valves. Two years later,
      he presented with severe necrotizing pancreatitis (Ranson's score 5, Balthazar's
      score 8). Viral and genetic testing came back negative; pancreatitis was
      attributed to the patient's treatments (prednisone, trimethoprim
      sulfamethoxazole, and everolimus). Twenty days later, necrotized pancreatic cysts
      had formed. Two drains were surgically inserted into the abdomen, and continuous
      cyst lavage was started with normal saline solution. Two days later, blood tests
      revealed severe hypernatremia and hypokalemia. We suspected unwanted peritoneal
      dialysis had occurred because of the high sodium chloride content and the absence
      of potassium in the normal saline solution being used for cyst lavage. We
      switched to a peritoneal dialysis solution for the lavage, leading to complete
      correction of hydroelectrolytic disorders. CONCLUSION: Acute pancreatitis is a
      frequent and potentially severe complication in CKD patients. It should be
      suspected in the presence of nonspecific symptoms, such as abdominal pain or
      vomiting. Rigorous monitoring of electrolytes is also mandatory for managing CKD
      patients with acute pancreatitis.

PMID- 29067526
TI  - Hypernatremia and acute pancreatitis in chronic kidney disease: back to the salt
      mines. Answers.

PMID- 29067524
TI  - Exploring the crizotinib resistance mechanism of NSCLC with the L1196M mutation
      using molecular dynamics simulation.
AB  - Crizotinib is an anticancer tyrosine kinase inhibitor that is approved for use as
      a first-line treatment for some non-small-cell lung cancers. L1196M is the most
      frequently observed mutation in NSCLC patients. This mutation, known as the
      gatekeeper mutation in the ALK kinase domain, confers resistance to crizotinib by
      sterically blocking the binding of the drug. However, the molecular mechanism of
      crizotinib resistance caused by the L1196M mutation is still unclear. Molecular
      dynamics simulation was therefore utilized in this study to investigate the
      mechanism by which the L1196M mutation may affect crizotinib resistance. Our
      results suggest that larger fluctuations in some important regions of the mutant
      complex compared to the wild-type complex may contribute to the resistance of the
      mutant complex to crizotinib. Also, mutation-induced alterations to the secondary
      structure of the complex as well as unstable hydrogen-bonding patterns in the A
      loop and P-loop regions decrease the total binding energy of the complex. This
      study therefore provides a molecular explanation for the resistance to crizotinib
      caused by the L1196M mutation, which could aid the design of more efficient and
      selective drugs.

PMID- 29067527
TI  - State-of-the-art immunosuppression protocols for pediatric renal transplant
      recipients.
AB  - Immunosuppressive protocols used in pediatric kidney transplantation have changed
      substantially within the last decade. Many transplant centers now focus on the
      use of tacrolimus and mycophenolate mofetil in combination with early steroid
      withdrawal, frequently combined with antibody induction therapy. However, this
      approach is mainly based on treatment efficacy and-compared to other
      immunosuppressive regimens used in this context-leads to higher rates of viral
      infections in patients. In this review I assess data from prospective,
      interventional trials of immunosuppressive therapy in pediatric kidney
      transplantation. However, since there is a paucity of randomized controlled
      trials, I also describe the results of studies with weaker designs. The
      advantages and disadvantages of different immunosuppressive strategies are
      discussed. Within this framework I suggest ideas for individualized
      immunosuppressive regimens based on different stratificators that could effect a
      change from a 'one size fits all' to a tailored approach for initial and
      maintenance immunosuppressive therapy after renal transplantation in the
      pediatric setting.

PMID- 29067528
TI  - A new parallel closing mechanism for the laminectomy rongeur makes it
      significantly more precise: a biomechanical and mechanical comparison study.
AB  - PURPOSE: To prove that a modified closing mechanism of the rongeur gives better
      precision compared to the old Kerrison rongeur. METHODS: Forty persons from the
      departments of orthopaedic surgery, urology and neurosurgery (35 orthopaedic, 2
      urology and 3 neurosurgery) took part in the study. All participants were asked
      to punch ten times in a first step with either the old Kerrison rongeur with the
      scissors-like handle or the modified punch with a new parallel closing mechanism.
      In a second step, they punched 10 times with the other instrument. Shaft movement
      in three dimensions was measured with a stereoscopic, contactless, full-field
      digital image correlation system. RESULTS: The new rongeur is significantly more
      precise with less movement in all three dimensions. The mechanical model of the
      new rongeur shows that the momentum needed to keep the tip at the initial
      position changes only minimally during the closing act on the new model.
      CONCLUSION: The new rongeur is more precise compared to the old Kerrison model.
      It is more robust against changes in the direction of the finger forces and may
      reduce soreness, fatigue and CTS in spine surgeons. LEVEL OF EVIDENCE: Not
      applicable: technical study.

PMID- 29067529
TI  - Codon usage of HIV regulatory genes is not determined by nucleotide composition.
AB  - Codon usage bias can be a result of either mutational bias or selection for
      translational efficiency and/or accuracy. Previous data has suggested that
      nucleotide composition constraint was the main determinant of HIV codon usage,
      and that nucleotide composition and codon usage were different between the
      regulatory genes, tat and rev, and other viral genes. It is not clear whether
      translational selection contributed to the codon usage difference and how
      nucleotide composition and translational selection interact to determine HIV
      codon usage. In this study, a model of codon bias due to GC composition with
      modification for the A-rich third codon position was used to calculate predicted
      HIV codon frequencies based on its nucleotide composition. The predicted codon
      usage of each gene was compared with the actual codon frequency. The predicted
      codon usage based on GC composition matched well with the actual codon
      frequencies for the structural genes (gag, pol and env). However, the codon usage
      of the regulatory genes (tat and rev) could not be predicted. Codon usage of the
      regulatory genes was also relatively unbiased showing the highest effective
      number of codons (ENC). Moreover, the codon adaptation index (CAI) of the
      regulatory genes showed better adaptation to human codons when compared to other
      HIV genes. Therefore, the early expressed genes responsible for regulation of the
      replication cycle, tat and rev, were more similar to humans in terms of codon
      usage and GC content than other HIV genes. This may help these genes to be
      expressed efficiently during the early stages of infection.

PMID- 29067530
TI  - Reply to a letter to the editor: inner nuclear layer cystoid spaces are a poor
      prognostic factor in typical age-related macular degeneration and polypoidal
      choroidal vasculopathy.

PMID- 29067532
TI  - Biometric evaluation of myopic eyes without posterior staphyloma:
      disproportionate ocular growth.
AB  - PURPOSE: To evaluate changes in the anterior segment of myopic eyes and assess
      anterior biometry as a function of axial length (AL). DESIGN: Retrospective
      investigational study. PARTICIPANTS: Patients evaluated for phakic intraocular
      lens surgery at a tertiary eye care centre. METHODS: Patients with corrected
      visual acuity > 20/40 and AL > 24.5 mm were included in the study. Posterior
      staphyloma and maculopathy were ruled out in all the patients, and 176 eyes were
      included for analysis. AL was measured with partial coherence interferometry,
      while keratometry, central corneal thickness (CCT), anterior chamber depth (ACD),
      and horizontal white to white (WTW) were measured with slit-scanning topography.
      Group 1 included 55 eyes with AL < 26.5 mm, group 2 had 57 eyes with AL between
      26.5 and 28.5 mm while group 3 had 64 eyes with AL > 28.5 mm. MAIN OUTCOME
      MEASURE: Correlation of AL with anterior biometry. RESULTS: The mean AL of the
      study eyes was 27.88 + 2.14 mm. The mean values of ACD (2.99 mm), CCT (0.52 mm),
      WTW (11.68 mm), and keratometry (43.62 D) were within the normal range. Overall,
      very weak correlations could be established between AL and CCT (R = 0.17, p =
      0.02), AL and keratometry (R = - 0.28, p < 0.001), and AL and WTW (R = 0.22, p =
      0.002), while ACD did not relate to AL significantly. The ACD and CCT did not
      relate significantly to AL in any of the three groups. Keratometry had a weak
      negative relation with AL in groups 1 and 2, while WTW had a weakly positive
      relation with AL in group 2 only. No variable had any significant relation with
      AL in group 3. CONCLUSION: There is disproportionate elongation of the eyeball in
      myopic patients with very weak or no correlation between anterior biometry and
      AL. This discord is more in longer eyes. Such a scenario can be challenging to a
      refractive surgeon treating highly myopic eyes and needs further evaluation.

PMID- 29067531
TI  - Microbial community differentiation between active and inactive sulfide chimneys
      of the Kolumbo submarine volcano, Hellenic Volcanic Arc.
AB  - Over the last decades, there has been growing interest about the ecological role
      of hydrothermal sulfide chimneys, their microbial diversity and associated
      biotechnological potential. Here, we performed dual-index Illumina sequencing of
      bacterial and archaeal communities on active and inactive sulfide chimneys
      collected from the Kolumbo hydrothermal field, situated on a geodynamic
      convergent setting. A total of 15,701 OTUs (operational taxonomic units) were
      assigned to 56 bacterial and 3 archaeal phyla, 133 bacterial and 16 archaeal
      classes. Active chimney communities were dominated by OTUs related to
      thermophilic members of Epsilonproteobacteria, Aquificae and Deltaproteobacteria.
      Inactive chimney communities were dominated by an OTU closely related to the
      archaeon Nitrosopumilus sp., and by members of Gammaproteobacteria,
      Deltaproteobacteria, Planctomycetes and Bacteroidetes. These lineages are closely
      related to phylotypes typically involved in iron, sulfur, nitrogen, hydrogen and
      methane cycling. Overall, the inactive sulfide chimneys presented highly diverse
      and uniform microbial communities, in contrast to the active chimney communities,
      which were dominated by chemolithoautotrophic and thermophilic lineages. This
      study represents one of the most comprehensive investigations of microbial
      diversity in submarine chimneys and elucidates how the dissipation of
      hydrothermal activity affects the structure of microbial consortia in these
      extreme ecological niches.

PMID- 29067533
TI  - Double-flanged-haptic and capsular tension ring or segment for sutureless
      fixation in zonular instability.
AB  - PURPOSE: This paper introduces a surgical technique for the sutureless management
      of zonular dialysis greater than 120 degrees  using a capsular tension segment
      (CTS) or a modified capsular tension ring (m-CTR; CTR with suturing eyelets) and
      a haptic removed from a 3-piece polypropylene IOL. METHODS: A CTR is used as
      normal. Cataract removal is followed by connection of the CTS or m-CTR to the
      single haptic and created using heat to make a flange in one haptic's extremity.
      The other extremity is placed in the CTS or m-CTR's central hole. The CTS or m
      CTR/flanged-haptic complex is introduced into the capsular bag and aligned with
      the weakest zonular quadrant. A 30-gauge needle guides the externalization of the
      free haptic extremity through the adjacent pars plana and creates a flange on the
      second haptic tip permitting intrascleral fixation of the CTS or m-CTR. RESULTS:
      The result is a successful IOL implantation with a sutureless technique.
      CONCLUSIONS: This double-flanged m-CTR/CTS technique allows suture-free option
      for managing zonular weakness or dialysis while performing cataract surgery.

PMID- 29067534
TI  - Mitigating effects of pollen during paraquat exposure on gene expression and
      pathogen prevalence in Apis mellifera L.
AB  - Honey bee (Apis mellifera L.) populations have been experiencing notable
      mortality in Europe and North America. No single cause has been identified for
      these dramatic losses, but rather multiple interacting factors are likely
      responsible (such as pesticides, malnutrition, habitat loss, and pathogens).
      Paraquat is one of the most widely used non-selective herbicides, especially in
      developing countries. This herbicide is considered slightly toxic to honey bees,
      despite being reported as a highly effective inducer of oxidative stress in a
      wide range of living systems. Here, we test the effects of paraquat on the
      expression of detoxification and antioxidant-related genes, as well as on the
      dynamics of pathogen titers. Moreover, we tested the effects of pollen as
      mitigating factor to paraquat exposure. Our results show significant changes in
      the expression of several antioxidant-related and detoxification-related genes in
      the presence of paraquat, as well as an increase of pathogens titers. Finally, we
      demonstrate a mitigating effect of pollen through the up-regulation of specific
      genes and improvement of survival of bees exposed to paraquat. The presence of
      pollen in the diet was also correlated with a reduced prevalence of Nosema and
      viral pathogens. We discuss the importance of honey bees' nutrition, especially
      the availability of pollen, on colony losses chronically reported in the USA and
      Europe.

PMID- 29067535
TI  - Prebending of osteosynthesis plate using 3D printed models to treat symptomatic
      os acromiale and acromial fracture.
AB  - BACKGROUND: A symptomatic os acromiale can lead to impingement syndrome and
      rotator cuff tendinopathy. An acromion fracture is often part of a more complex
      scapular trauma that needs stabilisation. METHODS: We developed a new technique
      using a three-dimensional (3D) model and a distal clavicle reconstruction plate
      to treat os acromiale and acromion fractures. Our hypothesis was that such an
      approach would be a useful addition to the existing techniques. First, a 3D model
      of the acromion was printed, then an osteosynthesis plate was pre-bent to fit the
      exact shape and curve of the acromion. We tested this technique and present
      reports on five patients, three with os acromiales and two with acromial
      fractures. We followed these patients during their rehabilitation and evaluated
      them using the Constant-Murley and the Disabilities of the Arm, Shoulder and Hand
      scores. RESULTS: In every case the fracture or non-union healed. If the surgery
      was performed before additional damage (such as an impingement syndrome)
      occurred, we saw that the patient's pain completely disappeared. This new
      technique also has other advantages because the surgeon can prepare the entire
      operation in advance, which reduces the duration of surgery. Another advantage of
      using a 3D model is that it can also be used to inform the patient and the
      surgical team about the planned operation. CONCLUSION: This new technique using a
      preoperative patient-customized plate is a good alternative for use in open
      reduction and internal fixation, particularly if the patient has no other
      conditions.

PMID- 29067536
TI  - Development of a Cell-Based Assay to Assess Binding of the proNGF Prodomain to
      Sortilin.
AB  - Sortilin was first identified based on its activity as part of intracellular
      protein sorting machinery. Recently, it was discovered that sortilin also acts as
      a cell surface receptor for the propeptide form of nerve growth factor (proNGF),
      progranulin, and neurotensin. The interaction of sortilin to these neurotrophic
      ligands is linked to diseases of the nervous system that lead to
      neurodegeneration and neuropathic pain. Blocking of the interaction of sortilin
      to these ligands may prevent or slow the progress of these nervous system
      disorders. In vitro screening assays for blocking compounds or peptides are part
      of the standard set of tools for drug discovery. However, assays for sortilin
      biology are not readily available to determine if the selected blocking agent
      inhibits sortilin activity on the surface of cells. We have developed a sortilin
      specific cell based assay to identify compounds that specifically block
      interaction between sortilin and proNGF prodomain. The assay system records both
      the presence of sortilin on the cell surface and the interaction with the pro
      domain of NGF. Fluorescent images of the sortilin expressing cells are analyzed
      for the presence of pro domain of NGF. Sortilin-positive and sortilin-negative
      cells within one well are concomitantly and automatically analyzed. Sortilin-pro
      domain interaction can be blocked dose dependently by neurotensin and synthetic
      compounds. The assay will facilitate the discovery of entities interfering with
      the binding of sortilin to the NGF pro domain. This assay can be modified to
      screen for inhibitors of the binding of ligands to other complex cell surface
      receptors.

PMID- 29067537
TI  - Posterior reversible encephalopathy syndrome (PRES) induced by pazopanib, a multi
      targeting tyrosine kinase inhibitor, in a patient with soft-tissue sarcoma: case
      report and review of the literature.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinical entity
      characterized by acute neurological symptoms such as severe headache, seizures,
      and visual disturbance, and by typical reversible lesion on brain magnetic
      resonance (MR) images. Since PRES is thought to be caused by vascular endothelial
      injury due to cytotoxic agents or acute systemic hypertension, the number of
      reports on PRES associated with angiogenesis inhibitors has been increasing.
      Although five cases that developed PRES due to pazopanib for renal cell carcinoma
      have already been reported, none of PRES due to pazopanib for soft-tissue sarcoma
      has been reported thus far. We describe a case of a 49-year-old woman with
      retroperitoneal soft-tissue sarcoma who developed PRES during pazopanib
      administration. Pazopanib at 800 mg/day was administered as her third-line
      treatment at relapse. After 38 days of pazopanib, she was admitted to our
      hospital with severe headache, vomiting, and systemic hypertension. The next day,
      she developed consciousness deterioration and visual disturbance together with
      exacerbated systemic hypertension. Brain MR images revealed hyper-intense signals
      on FLAIR sequences in the bilateral occipital lobes and the left thalamus.
      Intravenous nicardipine injection was immediately started to control her blood
      pressure and pazopanib was discontinued. Her symptoms gradually improved and
      disappeared on the fifth hospital day. After 2 weeks, hyper-intense signals on a
      FLAIR sequence disappeared completely. She restarted a low dose of pazopanib
      under good blood pressure control and experienced no subsequent recurrence of
      PRES.

PMID- 29067538
TI  - Inhibitors of apoptosis: clinical implications in cancer.
AB  - Inhibitor of apoptosis (IAP) family comprises a group of endogenous proteins that
      function as main regulators of caspase activity and cell death. They are
      considered the main culprits in evasion of apoptosis, which is a fundamental
      hallmark of carcinogenesis. Overexpression of IAP proteins has been documented in
      various solid and hematological malignancies, rendering them resistant to
      standard chemotherapeutics and radiation therapy and conferring poor prognosis.
      This observation has urged their exploitation as therapeutic targets in cancer
      with promising pre-clinical outcomes. This review describes the structural and
      functional features of IAP proteins to elucidate the mechanism of their anti
      apoptotic activity. We also provide an update on patterns of IAP expression in
      different tumors, their impact on treatment response and prognosis, as well as
      the emerging investigational drugs targeting them. This aims at shedding the
      light on the advances in IAP targeting achieved to date, and encourage further
      development of clinically applicable therapeutic approaches.

PMID- 29067539
TI  - Two-dimensional XD-GRASP provides better image quality than conventional 2D
      cardiac cine MRI for patients who cannot suspend respiration.
AB  - OBJECTIVES: Residual respiratory motion degrades image quality in conventional
      cardiac cine MRI (CCMRI). We evaluated whether a free-breathing (FB) radial
      imaging CCMRI sequence with compressed sensing reconstruction [extradimensional
      (e.g. cardiac and respiratory phases) golden-angle radial sparse parallel, or XD
      GRASP] could provide better image quality than a conventional Cartesian breath
      held (BH) sequence in an unselected population of patients undergoing clinical
      CCMRI. MATERIALS AND METHODS: One hundred one patients who underwent BH and FB
      imaging in a midventricular short-axis plane at a matching location were
      included. Visual and quantitative image analysis was performed by two blinded
      experienced readers, using a five-point qualitative scale to score overall image
      quality and visual signal-to-noise ratio (SNR) grade, with measures of noise and
      sharpness. End-diastolic and end-systolic left ventricular areas were also
      measured and compared for both BH and FB images. RESULTS: Image quality was
      generally better with the BH cines (overall quality grade for BH vs FB images 4
      vs 2.9, p < 0.001; noise 0.06 vs 0.08 p < 0.001; SNR grade 4.1 vs 3, p < 0.001),
      except for sharpness (p = 0.48). There were no significant differences between BH
      and FB images regarding end-diastolic or end-systolic areas (p = 0.35 and p =
      0.12). Eighteen of the 101 patients had poor BH image quality (grade 1 or 2). In
      this subgroup, the quality of the FB images was better (p = 0.0032), as was the
      SNR grade (p = 0.003), but there were no significant differences regarding noise
      and sharpness (p = 0.45 and p = 0.47). CONCLUSION: Although FB XD-GRASP CCMRI was
      visually inferior to conventional BH CCMRI in general, it provided improved image
      quality in the subgroup of patients with respiratory-motion-induced artifacts on
      BH images.

PMID- 29067541
TI  - Bone Morphogenic Protein-2 (rhBMP2)-Loaded Silk Fibroin Scaffolds to Enhance the
      Osteoinductivity in Bone Tissue Engineering.
AB  - There is an increasing demand for formulations of silk fibroin (SF) scaffolds in
      biomedical applications. SF was crosslinked via glutaraldehyde with
      osteoinductive recombinant human bone morphogenic protein-2 (rhBMP2) of different
      ratios viz. (i) 3% SF with no rhBMP2 (SF), (ii) 3% SF with equal amount of rhBMP2
      (SF+BMP2), and (iii) 12% SF with 3% of rhBMP2 (4SF+BMP2), and these solutions
      were used in electrospinning-based fabrication of nanoscaffolds for evaluating
      increased osteoinductive potential of SF scaffolds with rhBMP2. Stress-strain
      relationship suggested there is no loss in mechanical strength of fibers with
      addition of rhBMP2, and mechanical strength of scaffold was improved with
      increase in concentration of SF. rhBMP2 association increased the water retention
      capacity of scaffold as evident from swelling studies. Viability of hMSCs was
      found to be higher in conjugated scaffolds, and scaffolds do not exhibit any
      cytotoxicity towards guest cells. Cells were found to have higher alkaline
      phosphatase activity in conjugated scaffolds under in vitro and in vivo
      conditions which establishes the increased osteoinductivity of the novel
      construct. The scaffolds were found to be effective for in vivo bone formation as
      well.

PMID- 29067542
TI  - Women's Understanding and Attitudes towards Down Syndrome and Other Genetic
      Conditions in the Context of Prenatal Screening.
AB  - In order to explore the impact of potential new technologies in the area of
      prenatal screening, we conducted a baseline study using qualitative interviews to
      explore women's attitudes and knowledge regarding current and future prenatal
      screening technology and methods. Three cohorts were interviewed, including
      healthy women without children, healthy women with healthy children, and healthy
      women with children who have de novo genetic disorders. This study aimed to
      assess the baseline understanding and attitudes of women in Western Australia.
      Women from each cohort demonstrated adequate knowledge of the differences between
      screening and diagnostic tests, but were mostly unaware of the conditions for
      which screening is currently available except Down syndrome. Women who had
      children with de novo genetic conditions were generally aware of more genetic
      conditions than women with or without healthy children. Most women recognised the
      genetic basis for the conditions mentioned. Two thirds of women understood that
      Down syndrome is a chromosomal condition; just one third recognised that the
      phenotype is variable. Most women expressed a positive attitude towards Down
      syndrome. Social acceptance of children with Down syndrome was commonly mentioned
      as a concern. While the majority of women with children supported screening for
      Down syndrome, they emphasised that it must be an autonomous choice. General
      knowledge of genetic conditions illustrated that women are exposed to diverse
      conditions from lived experience as well as the media.

PMID- 29067540
TI  - Attachment and telomere length: more evidence for psychobiological connections
      between close relationships, health, and aging.
AB  - Individuals with a history of poor interpersonal relationships are more likely to
      demonstrate negative health outcomes than those who have had high quality
      relationships. We sought to evaluate how attachment orientations, stress-induced
      respiratory sinus arrhythmia (RSA), and self-reported stress were associated with
      length of telomeres measured from peripheral blood mononuclear cells.
      Participants (N = 213) completed self-report measures of attachment and stress.
      Measurement of RSA was conducted before and after a stressful task and a blood
      draw was completed for analysis of telomere length. Attachment orientations were
      not directly associated with telomere length; however, we found that high
      attachment anxiety was associated with shorter length of telomeres via high self
      reported stress. Attachment avoidance was also associated with telomere length
      via self-reported stress, but only among those with high stress-induced RSA.
      Exploratory analyses of T cell subsets indicated that stress was most strongly
      associated with telomeres from CD8CD28+ cells in comparison to CD8CD28- and CD4
      cells. Study findings indicate that attachment orientations are associated with
      telomere length via stress, providing novel insights into the mechanisms through
      which close relationships can impact health and aging.

PMID- 29067543
TI  - Maxillofacial surgery: the impact of the Great War on both sides of the trenches.
AB  - "War is the father and King of all", Heraclitus the obscure philosopher,
      declares. It certainly appears that the specialty of maxillofacial surgery was
      greatly advanced during WWI. This article focuses on the circumstances under
      which the specialty was developed, the significant events and the important
      figures that played a leading role in the advancement of a new fascinating
      surgical specialty. The literature leaves no doubt that trench warfare despite
      its devastating outcome for humanity has forged the shape of modern maxillofacial
      surgery.

PMID- 29067544
TI  - Rare case report of an aggressive follicular lymphoid hyperplasia in maxilla.
AB  - Follicular lymphoid hyperplasia is a very rare though benign reactive process of
      an unknown pathogenesis that may resemble a follicular lymphoma, clinically and
      histologically. Oral reactive follicular hyperplasia (RFH) has been described on
      the hard or soft palate and at the base of the tongue. We describe here the first
      case of RFH presenting as an aggressive tumor on the right posterior side of the
      maxilla in a 24-year-old male patient. The lesion had a clinical evolution of 18
      months and was noticed after the surgical extraction of the right third molar,
      although we cannot assume a cause-effect relation with that surgical event
      whatsoever. His medical history was unremarkable. Following an incisional biopsy,
      histological examination revealed lymphoid follicles comprised by germinal
      centers surrounded by well-defined mantle zones. The germinal centers were
      positive for Bcl-6, CD10, CD20, CD21, CD23, CD79a, and Ki-67, while negative for
      Bcl-2, CD2, CD3, CD5, and CD138. The mantle and interfollicular zones were
      positive for Bcl-2, CD2, CD3, CD5, CD20, and CD138. Both areas were diffusively
      positive for kappa and lambda, showing polyclonality. The patient underwent a
      vigorous curettage of the lesion with no reoccurrences at 36 months of follow-up.
      This case report demonstrates that morphologic and immunohistochemical analyses
      are crucial to differentiate RFH from follicular lymphoma, leading to proper
      management.

PMID- 29067546
TI  - 1H, 13C and 15N chemical shift assignment of lissencephaly-1 homology (LisH)
      domain homodimer of human two-hybrid-associated protein 1 with RanBPM (Twa1).
AB  - The CTLH complex is a large, highly conserved eukaryotic complex composed of
      eight proteins that has been associated to several cellular functions, more often
      described as an E3 ubiquitin ligase complex involved in protein degradation
      through ubiquitination but also via vacuole-dependent degradation. A common
      feature observed in several components of this complex is the presence of the
      domains lissencephaly-1 homology (LisH) and C-terminal to LisH (CTLH). The LisH
      domain is found in several proteins involved in chromosome segregation,
      microtubule dynamics, and cell migration. Also, this domain participates in
      protein dimerization, besides affecting protein half-life, and influencing in
      specific cellular localization. Among the proteins found in the CTLH complex,
      Twa1 (Two-hybrid-associated protein 1 with RanBPM), also known as Gid8 (glucose
      induced degradation protein 8 homolog) is the smallest, being a good model for
      structural studies by NMR. In this work we report the chemical shift assignments
      of the homodimeric LisH domain of Twa1, as a first step to determine its solution
      structure.

PMID- 29067545
TI  - Competing Motivations: Proactive Response Inhibition Toward Addiction-Related
      Stimuli in Quitting-Motivated Individuals.
AB  - We examined whether addiction-related cues impact proactive inhibition (the
      restraint of actions in preparation for stopping) in individuals who are
      motivated to quit gambling or cannabis use. In Study 1, treatment-seeking
      individuals with cannabis use disorder and matched controls performed a stop
      signal task that required them to inhibit categorizing cannabis or neutral
      pictures, and within varying levels of stop-signal probability. In Study 2, two
      groups of individuals, who applied to a voluntary self-exclusion program toward
      gambling, performed the stop-task following relaxation or gambling craving
      induction, with results compared to non-gamblers. Study 1 showed that despite
      being less efficient in proactive inhibition, individuals with cannabis use
      disorder exhibited heightened proactive inhibition toward cannabis cues. In Study
      2, proactive inhibition toward gambling cues was heightened in gamblers after
      craving, but the degree of proactive adjustment decreased as a function of
      induced changes in gambling-related motivation. Present findings demonstrate that
      exposure to addiction-related cues can modulate proactive inhibition in
      individuals who are motivated to restrict their addictive behaviors.

PMID- 29067548
TI  - Operating room waste: disposable supply utilization in neurointerventional
      procedures.
AB  - BACKGROUND: Operating rooms account for 70% of hospital waste, increasing
      healthcare costs and creating environmental hazards. Endovascular treatment of
      cerebrovascular pathologies has become prominent, and associated products highly
      impact the total cost of care. We investigated the costs of endovascular surgical
      waste at our institution. METHODS: Data from 53 consecutive endovascular
      procedures at the Radboud UMC Nijmegen from May to December 2016 were collected.
      "Unused disposable supply" was defined as one-time use items opened but not used
      during the procedure. Two observers cataloged the unused disposable supply for
      each case. The cost of each item was determined from the center supply catalog,
      and these costs were summed to determine the total cost of unused supply per
      case. RESULTS: Thirteen diagnostic cerebral digital subtraction angiographies
      (DSA) (24.5%) and 40 endovascular procedures (75.5%) were analyzed. Total
      interventional waste was 27,299.53 ? (mean 515.09 ? per procedure). While total
      costs of unused disposable supply were almost irrelevant for DSAs, they were
      consistent for interventional procedures (mean 676.49 ? per case). Aneurysm
      standard coiling had the highest impact on total interventional waste (mean
      1061.55 ?). Disposable interventional products had a very high impact on the
      surgical waste costs in the series of the neurointerventional procedures (95% of
      total waste). CONCLUSIONS: This study shows the impact of neurointerventional
      waste on the total care costs for cerebrovascular patients. This might reflect
      the tendency to anticipate needs and emergencies in neurointervention.
      Responsible use of disposable material can be achieved by educating operators and
      nurses and creating operator preference cards.

PMID- 29067549
TI  - Relationship of bipolar disorder with psychiatric comorbidity in the postpartum
      period-a scoping review.
AB  - Childbirth can trigger a variety of psychiatric disorders; however, no disorder
      is as profoundly affected by childbirth as bipolar disorder. Rates of psychiatric
      comorbidity especially anxiety disorders, obsessive compulsive disorder, and
      substance use disorders are quite high in individuals with bipolar disorder. The
      purpose of this scoping review is to ascertain the effect of childbirth on the
      relationship between the onset of bipolar disorder and comorbid psychiatric
      disorders. On June 27, 2017, a search of the Medline, PsycINFO, CINHAL, EMBASE,
      SCOPUS, COCHRANE, and ISI-Web of Science (WOS) databases was performed using the
      terms mental disorders, mental disease, major depressive disorder, major
      depression, depression, panic disorder, bipolar disorder, comorbidity, anxiety
      disorders, obsessive compulsive disorder, post-traumatic stress disorder,
      schizophrenia, eating disorders, reactive attachment disorder, childbirth,
      parturition, puerperium, postpartum, postpartum period and postnatal period.
      Reference lists of identified papers were manually searched, and all relevant
      papers published in English were included. A total of eight relevant articles
      were identified and included in the review. There is some evidence to suggest
      that occurrence of certain psychiatric disorders in the postpartum period may
      predict later onset of bipolar disorder. It is unknown whether childbirth raises
      the risk of postpartum recurrence of comorbid disorders. Whether patients who
      have past histories of psychiatric disorders are at increased risk for onset of
      bipolar disorder in the postpartum period also remains unclear. Additional
      research is needed to increase our understanding of the impact of childbirth on
      bipolar disorder and comorbid psychiatric disorders. A better understanding of
      this issue could lead to more accurate and timely detection, improved treatment
      planning, and optimal delivery of care for these disorders.

PMID- 29067547
TI  - Low levels of PSMA expression limit the utility of 18F-DCFPyL PET/CT for imaging
      urothelial carcinoma.
AB  - OBJECTIVE: To explore the clinical utility of PSMA-targeted 18F-DCFPyL PET/CT in
      patients with metastatic urothelial carcinoma. METHODS: Three patients with
      metastatic urothelial carcinoma were imaged with 18F-DCFPyL PET/CT. All lesions
      with perceptible radiotracer uptake above background were considered positive.
      Maximum standardized uptake values were recorded for each detected lesion and
      findings on 18F-DCFPyL PET/CT were compared to those on conventional imaging
      studies. To further explore PSMA as a molecular target of urothelial carcinoma,
      RNA-sequencing data from The Cancer Genome Atlas were used to compare the
      relative expression of PSMA among cases of bladder cancer, prostate cancer, and
      clear cell renal cell carcinoma. Additionally, immunohistochemical staining for
      PSMA was performed on a biopsy specimen from one of the imaged patients. RESULTS:
      18F-DCFPyL PET/CT allowed for the detection of sites of urothelial carcinoma,
      albeit with low levels of radiotracer uptake. Analysis of RNA-sequencing data
      revealed that bladder cancer had significantly lower levels of PSMA expression
      than both prostate cancer and clear cell renal cell carcinoma. Consistent with
      this observation, immunohistochemical staining of tissue from one of the imaged
      patients demonstrated a low level of neovascularization and nearly absent PSMA
      expression. CONCLUSION: The relatively scant expression of PSMA by urothelial
      carcinoma likely limits the utility of PSMA-targeted PET imaging of this
      malignancy. Future research efforts should focus on the development of other
      molecularly targeted imaging agents for urothelial carcinoma.

PMID- 29067550
TI  - Stability of the Pregnancy Obsessive-Compulsive Personality Disorder Symptoms
      Checklist.
AB  - Because stability over time is central to the definition of personality disorder,
      aim of the current study was to determine the stability of the Pregnancy
      Obsessive-Compulsive Personality Disorder (OCPD) Symptoms Checklist (N = 199
      women). Strong positive correlations between assessments at 32 weeks of pregnancy
      and 2 and 3-3.5 years after childbirth were found (r between .62-.72), and the
      group mean score did not change over time. The Pregnancy OCPD Symptoms Checklist
      assesses stable, trait-like symptoms of OCPD.

PMID- 29067553
TI  - Correction to: The Purine Salvage Pathway and the Restoration of Cerebral ATP:
      Implications for Brain Slice Physiology and Brain Injury.
AB  - The original version of Figure 4A contained superfluous text. This has now been
      removed.

PMID- 29067551
TI  - The association of exercise during pregnancy with trimester-specific and
      postpartum quality of life and depressive symptoms in a cohort of healthy
      pregnant women.
AB  - Few published studies have examined the relationship between exercise during
      pregnancy, quality of life (QOL), and postpartum depressive symptoms in healthy
      pregnant women. A prospective cohort of 578 healthy pregnant women were followed
      during their pregnancy through 6 months postpartum. Levels of self-reported
      exercise and QOL before, during, and following pregnancy were assessed using
      standardized questionnaires during each trimester of pregnancy and 6 months
      postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal
      Depression Scale (EPDS) at 28 weeks gestation and 6 weeks postpartum.
      Participants were classified as having "sufficient exercise" if they achieved at
      least 150 min of exercise per week. Sufficient exercisers reported significantly
      higher ratings on most domains of QOL during each trimester of pregnancy and in
      the postpartum follow-up, compared with insufficient exercisers. There were no
      significant between-group differences in depressive symptoms. In examining the
      impact of exercise during each trimester, active women who became sedentary
      during their third trimester demonstrated a decline in their QOL. Achieving
      recommended levels of exercise during pregnancy was associated with higher QOL
      during pregnancy and the postpartum in healthy pregnant women. Decreasing the
      amount of exercise during pregnancy was associated with reduced QOL. These
      results suggest that it may be important for health care professionals to counsel
      healthy pregnant women about both the benefits of being physically active during
      pregnancy, and to provide guidance on how to remain physically active during a
      healthy pregnancy.

PMID- 29067555
TI  - Posterior leaflet reconstruction using autologous pericardium in mitral repair.
AB  - A 75-year-old woman experienced recurrent mitral regurgitation caused mainly by a
      shrunken and tethered posterior mitral leaflet with a dilated left ventricle.
      Posterior leaflet motion was severely restricted. We successfully resolved the
      tethering and restored valve coaptation and competence using posterior leaflet
      reconstruction, which is a modified method of posterior leaflet augmentation
      using autologous pericardium. This technique can recover the posterior leaflet
      function by improving tissue volume and tethering.

PMID- 29067554
TI  - Extracellular Hsp70 induces inflammation and modulates LPS/LTA-stimulated
      inflammatory response in THP-1 cells.
AB  - Extracellular Hsp70 (eHsp70) can act as damage-associated molecular pattern
      (DAMP) via Toll-like receptors TLR2 and TLR4, and stimulate immune and
      inflammatory responses leading to sterile inflammation and propagation of already
      existing inflammation. It was found elevated in the blood of patients with
      chronic obstructive pulmonary disease (COPD), who might suffer occasional
      bacterial colonizations and infections. We used a monocytic THP-1 cell line as a
      cellular model of systemic compartment of COPD to assess inflammatory effects of
      eHsp70 when present alone or together with bacterial products lypopolysaccharide
      (LPS) and lypoteichoic acid (LTA). THP-1 cells were differentiated into
      macrophage-like cells and treated with various concentrations of recombinant
      human Hsp70 protein (rhHsp70), LPS (TLR4 agonist), LTA (TLR2 agonist), and their
      combinations for 4, 12, 24, and 48 h. Concentrations of IL-1alpha, IL-6, IL-8,
      and TNF-alpha were determined by ELISA. Cell viability was assessed by MTS assay,
      and mode of cell death by luminometric measurements of caspases-3/7, -8, and -9
      activities. rhHsp70 showed cell protecting effect by suppressing caspases-3/7
      activation, while LPS provoked cytotoxicity through caspases-8 and -3/7 pathway.
      Regarding inflammatory processes, rhHsp70 alone induced secretion of IL-1alpha
      and IL-8, but had modulatory effects on release of all four cytokines when
      applied together with LPS or LTA. Combined effect with LPS was mainly
      synergistic, and with LTA mainly antagonistic, although it was cytokine- and time
      dependent. Our results confirmed pro-inflammatory function of extracellular
      Hsp70, and suggest its possible implication in COPD exacerbations caused by
      bacterial infection through desensitization or inappropriate activation of TLR2
      and TLR4 receptors.

PMID- 29067556
TI  - Thoracoscopic resection of esophageal cancer with a tracheal diverticulum.
AB  - Tracheal diverticulum, a benign entity characterized by single or multiple
      invaginations of the tracheal wall, is commonly asymptomatic and detected
      incidentally. We report the case of a 76-year-old man with a tracheal
      diverticulum who underwent thoracoscopic esophagectomy with a three-field
      lymphadenectomy for middle thoracic esophageal cancer. The tracheal diverticulum
      was located at the right posterolateral region of the trachea, which overlapped
      the region of dissection of the right recurrent laryngeal nerve lymph nodes.
      Paratracheal lymph node dissection is an important surgical procedure for
      thoracic esophageal cancer. In such cases, there is a risk of misidentifying a
      tracheal diverticulum as an enlarged lymph node and injuring it. Injury of a
      tracheal diverticulum causes serious complications such as mediastinal emphysema,
      mediastinitis, and pulmonary fistula. It is important to recognize its existence
      preoperatively and perform accurate lymph node dissection by taking full
      advantage of the magnified visual effect provided by thoracoscopic surgery.

PMID- 29067557
TI  - Prevalence of Co-existing Autoimmune Disease in Rheumatoid Arthritis: A Cross
      Sectional Study.
AB  - INTRODUCTION: Many autoimmune diseases, including rheumatoid arthritis (RA),
      share common mechanisms; however, population-based studies of the magnitude of
      multiple autoimmune diseases in patients with RA have not been performed.
      METHODS: We conducted a cross-sectional study using a US administrative
      healthcare thcare claims database to screen for prevalence of multiple autoimmune
      diseases in patients with RA and osteoarthritis (OA). Each patient diagnosed with
      RA between January 1, 2006 and September 30, 2014 was age- and sex-matched with
      five patients with OA. The prevalence of 37 pre-specified autoimmune diseases
      during the 24-month period before and after RA or OA diagnosis was compared.
      RESULTS: Overall, 286,601 patients with RA and 992,838 matched patients (from
      1,421,624 records) with OA were evaluated. During the baseline period, at least
      one and more than one autoimmune diseases were identified in 24.3% and 6.0% of
      patients with RA compared with 10.5% and 1.4% of patients with OA, respectively.
      Highest prevalence rates for patients with RA were for systemic lupus
      erythematosus (3.8% versus 0.7% for OA) and psoriatic arthritis (3.2% versus
      0.4%). Highest odds ratios (ORs) comparing RA with OA were for the prevalence of
      ankylosing spondylitis (OR 8.0; 95% CI 7.6, 8.5) and psoriatic arthritis (OR 7.8;
      95% CI 7.6, 8.1). CONCLUSION: Patients with RA have more concurrent autoimmune
      diseases than patients with OA. These data suggest that the interrelationship
      between RA and other autoimmune diseases, and outcomes associated with the
      occurrence of multiple autoimmune diseases, may play an important role in disease
      understanding, management, and treatment decisions. FUNDING: Bristol-Myers
      Squibb.

PMID- 29067558
TI  - Oral appliance treatment outcome can be predicted by continuous positive airway
      pressure in moderate to severe obstructive sleep apnea.
AB  - BACKGROUND: Studies show that the therapeutic CPAP pressure is associated with
      oral appliance (OA) treatment outcome in obstructive sleep apnea (OSA) patients.
      However, these studies included either CPAP adherent patients using fixed
      pressure devices, or partly CPAP non-adherent patients using fixed pressure or
      auto-adjusting (auto-CPAP) devices. In many countries, auto-CPAP is predominately
      used, and only those non-adherent to therapy need a change to OA. Therefore,
      studies examining the relationship between CPAP pressures and OA treatment
      outcome should focus on patients non-adherent to auto-CPAP. PURPOSE: The purpose
      of this paper is to assess if CPAP pressures predicted OA treatment outcome in
      patients non-adherent to auto-CPAP therapy. METHODS: The OA treatment responders
      and non-responders were defined by two success criteria ((1) AHI < 5; (2) 5 <=
      AHI < 10 and > 50% AHI reduction). Logistic regression analyses were performed
      for CPAP pressures and baseline variables. ROC curve analyses were used to
      identify CPAP pressure cutoff values, alone and combined with other explanatory
      variables, predicting the OA treatment outcome. RESULTS: Eighty-seven patients
      with moderate or severe OSA were included. Maximum CPAP pressures (CPAPmax) were
      higher in non-responders by both criteria and were, together with baseline AHI,
      associated with the OA treatment outcome in multivariate regression analyses. ROC
      curves identified an optimal CPAPmax cutoff of 12 cm H2O, corresponding to a
      positive predictive value (PPV) of 0.85 in predicting non-response using
      criterion 1. A prediction model combining CPAPmax > 12 and baseline AHI >= 30 had
      a PPV of 1.0 for non-response by both criteria. CONCLUSIONS: Maximum CPAP
      pressure was a moderate predictor of OA treatment outcome, but combined with
      baseline AHI, the ability to identify OA non-responders was high.

PMID- 29067560
TI  - A memorial tribute to Michael Freeman, FRCP(C), FACC.

PMID- 29067559
TI  - Using eco-physiological traits to understand the realized niche: the role of
      desiccation tolerance in Chagas disease vectors.
AB  - Small ectotherms, such as insects, with high surface area-to-volume ratios are
      usually at risk of dehydration in arid environments. We hypothesize that
      desiccation tolerance in insects could be reflected in their distribution, which
      is limited by areas with high relative values of water vapor pressure deficit
      (VPD) (e.g., hot and dry). The main goal of this study was to explore whether
      incorporation of eco-physiological traits such as desiccation tolerance in arid
      environments can improve our understanding of species distribution models (SDM).
      We use a novel eco-physiological approach to understand the distribution and the
      potential overlap with their fundamental niche in triatomine bugs, Chagas disease
      vectors. The desiccation dimension for T. infestans, T. delpontei, T. dimidiata,
      and T. sordida niches seems to extend to very dry areas. For T. vitticeps, xeric
      areas seem to limit the geographical range of their realized niche. The maximum
      VPD limits the western and southern distributions of T. vitticeps, T. delpontei,
      and T. patagonica. All species showed high tolerance to desiccation with survival
      times (35  degrees C-RH ~ 15%) ranging from 24 to 38 days, except for T.
      dimidiata (9 days), which can be explained by a higher water-loss rate, due to a
      higher cuticular permeability along with a higher critical water content. This
      approach indicates that most of these triatomine bugs could be exploiting the
      dryness dimension of their fundamental niche. Incorporating such species-specific
      traits in studies of distribution, range, and limits under scenarios of changing
      climate could enhance predictions of movement of disease-causing vectors into
      novel regions.

PMID- 29067561
TI  - ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 Appropriate Use Criteria for
      Multimodality Imaging in Valvular Heart Disease : A Report of the American
      College of Cardiology Appropriate Use Criteria Task Force, American Association
      for Thoracic Surgery, American Heart Association, American Society of
      Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society,
      Society for Cardiovascular Angiography and Interventions, Society of
      Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic
      Resonance, and Society of Thoracic Surgeons.
AB  - This document is 1 of 2 companion appropriate use criteria (AUC) documents
      developed by the American College of Cardiology, American Association for
      Thoracic Surgery, American Heart Association, American Society of
      Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society,
      Society for Cardiovascular Angiography and Interventions, Society of
      Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic
      Resonance, and Society of Thoracic Surgeons. This document addresses the
      evaluation and use of multimodality imaging in the diagnosis and management of
      valvular heart disease, whereas the second, companion document addresses this
      topic with regard to structural heart disease. Although there is clinical
      overlap, the documents addressing valvular and structural heart disease are
      published separately, albeit with a common structure. The goal of the companion
      AUC documents is to provide a comprehensive resource for multimodality imaging in
      the context of valvular and structural heart disease, encompassing multiple
      imaging modalities.Using standardized methodology, the clinical scenarios
      (indications) were developed by a diverse writing group to represent patient
      presentations encountered in everyday practice and included common applications
      and anticipated uses. Where appropriate, the scenarios were developed on the
      basis of the most current American College of Cardiology/American Heart
      Association guidelines.A separate, independent rating panel scored the 92
      clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9
      indicate that a modality is considered appropriate for the clinical scenario
      presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate
      for the clinical scenario, and scores of 1 to 3 indicate that a modality is
      considered rarely appropriate for the clinical scenario.The primary objective of
      the AUC is to provide a framework for the assessment of these scenarios by
      practices that will improve and standardize physician decision making. AUC
      publications reflect an ongoing effort by the American College of Cardiology to
      critically and systematically create, review, and categorize clinical situations
      where diagnostic tests and procedures are utilized by physicians caring for
      patients with cardiovascular diseases. The process is based on the current
      understanding of the technical capabilities of the imaging modalities examined.

PMID- 29067562
TI  - Knee Implant Loosening Detection: A Vibration Analysis Investigation.
AB  - Knee implant loosening is mainly caused by the weakness of the prosthesis-bone
      interface and is the main reason for surgical revisions. However, pre-operative
      diagnosis is difficult due to lack of accurate tests. In this study, we developed
      a vibration-based system to detect the loosening of the tibial implant of an
      instrumented knee prosthesis. The proposed system includes an instrumented
      vibrator for transcutaneous stimulation of the bone in a repeatable manner, and
      accelerometer sensors integrated into the implants to measure the propagated
      vibration. A coherence-based detection technique was proposed to distinguish the
      loosened implants from the secure ones. Fourteen ex vivo lower limbs were used,
      on which the knee prosthesis was implanted, and harmonic-forced vibration was
      applied on the tibia. The input-output coherence measure provided 92.26%
      accuracy, a high sensitivity (91.67%) and specificity (92.86%). This technique
      was benchmarked against power spectrum based analysis of the propagated vibration
      to the implant. In particular, loosening detection based on new peak appearance,
      peak shift, and peak flattening in power spectra showed inferior performance to
      the proposed coherence-based technique. As such, application of vibration on our
      instrumented knee prosthesis together with input-output coherence analysis
      enabled us to distinguish the secure from loose implants.

PMID- 29067563
TI  - Using a Novel In Vitro Fontan Model and Condition-Specific Real-Time MRI Data to
      Examine Hemodynamic Effects of Respiration and Exercise.
AB  - Several studies exist modeling the Fontan connection to understand its
      hemodynamic ties to patient outcomes (Chopski in: Experimental and Computational
      Assessment of Mechanical Circulatory Assistance of a Patient-Specific Fontan
      Vessel Configuration. Dissertation, 2013; Khiabani et al. in J Biomech 45:2376
      2381, 2012; Taylor and Figueroa in Annu Rev Biomed 11:109-134, 2009; Vukicevic et
      al. in ASAIO J 59:253-260, 2013). The most patient-accurate of these studies
      include flexible, patient-specific total cavopulmonary connections. This study
      improves Fontan hemodynamic modeling by validating Fontan model flexibility
      against a patient-specific bulk compliance value, and employing real-time phase
      contrast magnetic resonance flow data. The improved model was employed to acquire
      velocity field information under breath-held, free-breathing, and exercise
      conditions to investigate the effect of these conditions on clinically important
      Fontan hemodynamic metrics including power loss and viscous dissipation rate. The
      velocity data, obtained by stereoscopic particle image velocimetry, was
      visualized for qualitative three-dimensional flow field comparisons between the
      conditions. Key hemodynamic metrics were calculated from the velocity data and
      used to quantitatively compare the flow conditions. The data shows a multi
      factorial and extremely patient-specific nature to Fontan hemodynamics.

PMID- 29067564
TI  - Clinically relevant radioresistant cell line: a simple model to understand cancer
      radioresistance.
AB  - Radiotherapy (RT) is one of the major modalities for the treatment of human
      cancers and has been established as an excellent local treatment for malignant
      tumors. Conventional fractionated RT consists of 2-Gy X-rays, fractionated once a
      day, 5 days a week for 5-7 weeks in total 60 Gy. The efficacy of RT depends on
      the existence of radioresistant cells, which remains one of the most critical
      obstacles in RT and radio-chemotherapy. To improve the efficacy of RT,
      understanding the characteristics of radioresistant cells is one of the important
      subjects in radiation biology. Several studies have been reported to find out
      molecules implicated in radioresistance. However, it is noteworthy that cellular
      radioresistance has been mainly studied among cells with different genetic
      backgrounds and different origins. Therefore, making a system to compare between
      radioresistant and sensitive cells with the isogenic background is required. In
      this review, some aspects of cellular radioresistance mainly focusing on
      clinically relevant radioresistant (CRR) cell lines that can continue to
      proliferate even under exposure to 2-Gy X-rays, once a day, for more than 30
      days, which is consistent with the conventional fractionated RT are discussed.

PMID- 29067565
TI  - Simple, mild, one-step labelling of proteins with gallium-68 using a
      tris(hydroxypyridinone) bifunctional chelator: a 68Ga-THP-scFv targeting the
      prostate-specific membrane antigen.
AB  - BACKGROUND: Labelling proteins with gallium-68 using bifunctional chelators is
      often problematic because of unsuitably harsh labelling conditions such as low pH
      or high temperature and may entail post-labelling purification. To determine
      whether tris(hydroxypyridinone) (THP) bifunctional chelators offer a potential
      solution to this problem, we have evaluated the labelling and biodistribution of
      a THP conjugate with a new single-chain antibody against the prostate-specific
      membrane antigen (PSMA), an attractive target for staging prostate cancer (PCa).
      A single-chain variable fragment (scFv) of J591, a monoclonal antibody that
      recognises an external epitope of PSMA, was prepared in order to achieve
      biokinetics matched to the half-life of gallium-68. The scFv, J591c-scFv, was
      engineered with a C-terminal cysteine. RESULTS: J591c-scFv was produced in
      HEK293T cells and purified by size-exclusion chromatography. A maleimide THP
      derivative (THP-mal) was coupled site-specifically to the C-terminal cysteine
      residue. The THP-mal-J591c-scFv conjugate was labelled with ammonium acetate
      buffered gallium-68 from a 68Ge/68Ga generator at room temperature and neutral
      pH. The labelled conjugate was evaluated in the PCa cell line DU145 and its PSMA
      overexpressing variant in vitro and xenografted in SCID mice. J591c-scFv was
      produced in yields of 4-6 mg/l culture supernatant and efficiently coupled with
      the THP-mal bifunctional chelator. Labelling yields > 95% were achieved at room
      temperature following incubation of 5 MUg conjugate with gallium-68 for 5 min
      without post-labelling purification. 68Ga-THP-mal-J591c-scFv was stable in serum
      and showed selective binding to the DU145-PSMA cell line, allowing an IC50 value
      of 31.5 nM to be determined for unmodified J591c-scFv. Serial PET/CT imaging
      showed rapid, specific tumour uptake and clearance via renal elimination.
      Accumulation in DU145-PSMA xenografts at 90 min post-injection was 5.4 +/-
      0.5%ID/g compared with 0.5 +/- 0.2%ID/g in DU145 tumours (n = 4). CONCLUSIONS:
      The bifunctional chelator THP-mal enabled simple, rapid, quantitative, one-step
      room temperature radiolabelling of a protein with gallium-68 at neutral pH
      without a need for post-labelling purification. The resultant gallium-68 complex
      shows high affinity for PSMA and favourable in vivo targeting properties in a
      xenograft model of PCa.

PMID- 29067567
TI  - Effect of incubation duration, growth temperature, and abiotic surface type on
      cell surface properties, adhesion and pathogenicity of biofilm-detached
      Staphylococcus aureus cells.
AB  - The goal of this study was to investigate the effect of growth conditions such as
      the temperature (20, 30 and 37  degrees C), incubation duration (24 and 48 h) and
      surface type (stainless steel and polycarbonate) on the cell surface
      physicochemical properties and adhesion to abiotic surfaces of biofilm-detached
      and planktonic Staphylococcus aureus cells. This study tested also the hypothesis
      that S. aureus planktonic cells exhibit distinct pathogenic properties compared
      with their sessile counterparts. The results showed that the changes of the
      growth conditions promoted changes in the zeta potential, hydrophobicity,
      electron donor/acceptor character of the studied cell populations. Biofilm
      detached cells showed a greater adhesion to stainless steel and polycarbonate
      compared with planktonic cells. Compared with planktonic cells, sessile ones
      showed higher cytotoxic effect against HeLa cells, DNase activity, and
      siderophore levels. The higher cytotoxic effect and production of DNase and
      siderophore increased with the increase of temperature and duration of
      incubations. Based on the obtained data, the S. aureus biofilm-detached cells
      were found to be distinct in many physiological properties compared with their
      planktonic counterparts.

PMID- 29067566
TI  - Diet, Gut Microbiota, and Vitamins D + A in Multiple Sclerosis.
AB  - Central to the understanding of the relationships between diet, gut microbiota,
      and vitamins D and A in multiple sclerosis is low-grade inflammation, which is
      involved in all chronic inflammatory diseases and is influenced by each of the
      above effectors. We show that food components have either proinflammatory or anti
      inflammatory effects and influence both the human metabolism (the "metabolome")
      and the composition of gut microbiota. Hypercaloric, high-animal-fat Western
      diets favor anabolism and change gut microbiota composition towards dysbiosis.
      Subsequent intestinal inflammation leads to leakage of the gut barrier,
      disruption of the blood-brain barrier, and neuroinflammation. Conversely, a
      vegetarian diet, rich in fiber, is coherent with gut eubiosis and a healthy
      condition. Vitamin D levels, mainly insufficient in a persistent low-grade
      inflammatory status, can be restored to optimal values only by administration of
      high amounts of cholecalciferol. At its optimal values (>30 ng/ml), vitamin D
      requires vitamin A for the binding to the vitamin D receptor and exert its anti
      inflammatory action. Both vitamins must be supplied to the subjects lacking
      vitamin D. We conclude that nutrients, including the nondigestible dietary
      fibers, have a leading role in tackling the low-grade inflammation associated
      with chronic inflammatory diseases. Their action is mediated by gut microbiota
      and any microbial change induced by diet modifies host-microbe interactions in a
      consequent way, to improve the disease or worsen it.

PMID- 29067568
TI  - Anemia at pediatric intensive care unit discharge: prevalence and risk markers.
AB  - BACKGROUND: Anemia is prevalent at pediatric intensive care unit (PICU) admission
      and incident during PICU stay, but little is known about anemia at PICU discharge
      . Anemia after critical illness is an important issue because it could impact
      post-PICU outcome. We aimed to estimate the prevalence of anemia at PICU
      discharge and to determine its risk markers. METHODS: This is an ancillary study
      of a prospective observational study on transfusion practices conducted in the
      PICU of a tertiary care children's hospital. All children consecutively admitted
      to the PICU during a 1-year period were considered for inclusion. Data were
      prospectively collected from medical charts, except for hemoglobin (Hb) levels at
      PICU and hospital discharge that were collected retrospectively. Anemia was
      defined by an Hb concentration below the lower limit of the normal range for age.
      RESULTS: Among the 679 children retained for analysis, 390 (57.4%) were anemic at
      PICU discharge. After multivariate adjustment, anemia at PICU admission was the
      strongest risk marker of anemia at PICU discharge. The strength of this
      association varied according to age (interaction): The odds ratio (OR) (95% CI)
      of anemia at PICU discharge was 4.85 (1.67-14.11) for 1-5-month-old infants
      anemic versus not anemic at PICU admission, and it was 73.13 (13.43, 398.19) for
      adolescents anemic versus not anemic at PICU admission. Children admitted after a
      non-cardiac surgery had an increased risk of anemia at PICU discharge [OR 2.30
      (1.37, 3.88), p = 0.002]. The proportion of anemic children differed between age
      categories, while the median Hb level did not exhibit significant variations
      according to age. CONCLUSIONS: Anemia is highly prevalent at PICU discharge and
      is strongly predicted by anemia at PICU admission. The usual age-based
      definitions of anemia may not be relevant for critically ill children. The
      consequences of anemia at PICU discharge are unknown and deserve further
      scrutiny.

PMID- 29067569
TI  - Anti-tumor Study of Chondroitin Sulfate-Methotrexate Nanogels.
AB  - Self-assembly nanogels (NGs) were formed by bioconjugating methotrexate (MTX)
      with chondroitin sulfate (CS). MTX-CS NGs can greatly enhance the solubility and
      improve the delivery efficacy of MTX due to the CD44 binding property of CS. Vivo
      experiments revealed that MTX-CS NGs showed less toxicity than MTX. MTX-CS NGs
      can improve the anti-tumor effect while reducing the side effects of MTX. Due to
      their CD44 binding property, chondroitin sulfate-drug conjugates could be a
      promising and efficient platform for improving the solubility of sparingly
      soluble drug molecules as well as targeted delivery to cancer cells and tumor
      tissues.

PMID- 29067570
TI  - An Efficient Pipeline for Abdomen Segmentation in CT Images.
AB  - Computed tomography (CT) scans usually include some disadvantages due to the
      nature of the imaging procedure, and these handicaps prevent accurate abdomen
      segmentation. Discontinuous abdomen edges, bed section of CT, patient
      information, closeness between the edges of the abdomen and CT, poor contrast,
      and a narrow histogram can be regarded as the most important handicaps that occur
      in abdominal CT scans. Currently, one or more handicaps can arise and prevent
      technicians obtaining abdomen images through simple segmentation techniques. In
      other words, CT scans can include the bed section of CT, a patient's diagnostic
      information, low-quality abdomen edges, low-level contrast, and narrow histogram,
      all in one scan. These phenomena constitute a challenge, and an efficient
      pipeline that is unaffected by handicaps is required. In addition, analysis such
      as segmentation, feature selection, and classification has meaning for a real
      time diagnosis system in cases where the abdomen section is directly used with a
      specific size. A statistical pipeline is designed in this study that is
      unaffected by the handicaps mentioned above. Intensity-based approaches,
      morphological processes, and histogram-based procedures are utilized to design an
      efficient structure. Performance evaluation is realized in experiments on 58 CT
      images (16 training, 16 test, and 26 validation) that include the abdomen and one
      or more disadvantage(s). The first part of the data (16 training images) is used
      to detect the pipeline's optimum parameters, while the second and third parts are
      utilized to evaluate and to confirm the segmentation performance. The
      segmentation results are presented as the means of six performance metrics. Thus,
      the proposed method achieves remarkable average rates for
      training/test/validation of 98.95/99.36/99.57% (jaccard), 99.47/99.67/99.79%
      (dice), 100/99.91/99.91% (sensitivity), 98.47/99.23/99.85% (specificity),
      99.38/99.63/99.87% (classification accuracy), and 98.98/99.45/99.66% (precision).
      In summary, a statistical pipeline performing the task of abdomen segmentation is
      achieved that is not affected by the disadvantages, and the most detailed abdomen
      segmentation study is performed for the use before organ and tumor segmentation,
      feature extraction, and classification.

PMID- 29067571
TI  - Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats
      through the inhibition of NF-kB pathway.
AB  - AIM: The aim of the present study is to investigate the protective effects of
      Foeniculum vulgare essential oil on intestinal inflammation through the
      inhibition of NF-kB pathway in acetic acid-induced rat colitis. METHODS: Acute
      colitis was induced by intra-rectal administration of 2 mL of diluted acetic acid
      (4%) solution. Two hours after the induction of colitis, 0.2% tween 80 in normal
      saline, dexamethasone (2 mg/kg) and F. vulgare essential oil (100, 200, 400
      mg/kg) were administered to the animals by oral gavage and continued for 5
      consecutive days. Assessment of macroscopic and microscopic lesions was done. MPO
      activity was evaluated by biochemical method. Furthermore, TNF-alpha activity was
      detected by immunohistochemistry (IHC) and the expression level of p-NF-kB p65
      protein was measured by western blot analysis. RESULTS: Dexamethasone and F.
      vulgare essential oil (200, 400 mg/kg) reduced the macroscopic and microscopic
      lesions compared to the acetic acid group (p < 0.01, p < 0.001). In addition,
      these agents decreased the activity of MPO (p < 0.01, p < 0.001) and the
      expression of TNF-alpha positive cells (p < 0.05, p < 0.01, p < 0.001) in the
      colon tissue compared to acetic acid group. Furthermore, they inhibited acetic
      acid-induced expression of p-NF-kB p65 protein (p < 0.05, p < 0.001). CONCLUSION:
      It is proposed that the anti-inflammatory activity of F. vulgare essential oil on
      acetic acid-induced colitis in rats may involve the inhibition of NF-kB pathway.

PMID- 29067572
TI  - Age- and gender-specific epidemiology, treatment patterns, and economic burden of
      osteoporosis and associated fracture in Taiwan between 2009 and 2013.
AB  - : This nationwide study investigated the epidemiology, treatment patterns, and
      economic burden of osteoporosis and associated fracture in Taiwan. The treatment
      of osteoporosis is alarmingly suboptimal, considering the significantly increased
      economic burden of major osteoporotic fracture. Osteoporosis men received lesser
      anti-osteoporosis drugs but had higher incremental costs attributable to
      osteoporotic fractures. PURPOSE: This nationwide study investigated the
      epidemiology, treatment patterns, and economic burden of osteoporosis and
      associated fracture between 2009 and 2013 in Taiwan. METHODS: We used the
      National Health Insurance Research Database as our data source. The prevalence of
      diagnosed osteoporosis and major osteoporotic fractures was calculated annually
      from 2009 to 2013, stratified by age and gender. Osteoporosis patients who
      received any prescription of anti-osteoporosis drugs during each fiscal year were
      defined as osteoporosis patients under treatment. Healthcare utilization and
      associated direct medical costs were used to quantify the economic burden of
      osteoporosis. For patients who encountered major osteoporotic fracture, the
      incremental changes of direct medical costs attributable to fracture using a pre-
      and post-quasi-experimental design were estimated. Furthermore, we compared the
      annual direct medical costs of patients who encountered major osteoporotic
      fracture with those diagnosed osteoporosis only and with the general population.
      RESULTS: The prevalence of diagnosed osteoporosis increased with age, with the
      highest rate among those aged 80 and older. Overall, less than one-third of women
      and only 10% of men received anti-osteoporosis drugs among osteoporosis patients.
      The annual direct medical costs for osteoporosis patients increased steadily from
      2009 to 2013. The total medical costs and incremental change of direct medical
      costs were higher in men than those in women. CONCLUSION: We found the treatment
      of osteoporosis to be alarmingly suboptimal, considering the significantly
      increased economic burden of major osteoporotic fracture also identified in this
      study. Osteoporosis men received lesser anti-osteoporosis drugs but had higher
      incremental costs attributable to major osteoporotic fractures.

PMID- 29067573
TI  - Iron uptake and storage in the HAB dinoflagellate Lingulodinium polyedrum.
AB  - The iron uptake and storage systems of terrestrial/higher plants are now
      reasonably well understood with two basic strategies being distinguished:
      Strategy I involves the induction of an Fe(III)-chelate reductase
      (ferrireductase) along with Fe(II) or Fe(III) transporter proteins while strategy
      II plants have evolved sophisticated systems based on high-affinity, iron
      specific, binding compounds called phytosiderophores. In contrast, there is
      little knowledge about the corresponding systems in marine, plant-like lineages.
      Herein we report a study of the iron uptake and storage mechanisms in the harmful
      algal bloom dinoflagellate Lingulodinium polyedrum. L. polyedrum is an armored
      dinoflagellate with a mixotrophic lifestyle and one of the most common bloom
      species on Southern California coast widely noted for its bioluminescent
      properties and as a producer of yessotoxins. Short term radio-iron uptake studies
      indicate that iron is taken up by L. polyedrum in a time dependent manner
      consistent with an active transport process. Based on inhibitor and other studies
      it appears that a reductive-oxidative pathway such as that found in yeast and the
      green alga Chlamydomonas reinhardtii is likely. Of the various iron sources
      tested vibrioferrin, a photoactive and relatively weak siderophore produced by
      potentially mutualistic Marinobacter bacterial species, was the most efficient.
      Other more stable and non-photoactive siderophores such as ferrioxamine E were
      ineffective. Several pieces of data including long term exposure to 57Fe using
      Mossbauer spectroscopy suggest that L. polyedrum does not possess an iron storage
      system but rather presumably relies on an efficient iron uptake system, perhaps
      mediated by mutualistic interactions with bacteria.

PMID- 29067574
TI  - Predictive factors of weight regain following laparoscopic Roux-en-Y gastric
      bypass.
AB  - BACKGROUND: Strategies to address weight recidivism following Roux-en-Y gastric
      bypass (RYGB) could be developed if patients at risk were identified in advance.
      This study aimed to determine factors that predict weight regain. METHODS:
      Retrospective review was performed of patients who underwent laparoscopic RYGB at
      a single institution over 10 years. Group-based modeling was used to estimate
      trajectories of weight regain after nadir and stratify patients based on percent
      weight change (%WC). RESULTS: Three trajectories were identified from 586
      patients: 121 had ongoing weight loss, 343 were weight stable, and 122 regained
      weight. Male sex (p = 0.020) and white race (p < 0.001) were associated with
      stable weight or weight regain. Being from a neighborhood of socioeconomic
      advantage (p = 0.035) was associated with weight regain. Patients with weight
      regain experienced improved percent weight loss (%WL) at nadir (p < 0.001) and
      DeltaBMI (p = 0.002), yet they had higher weight and BMI and lower %WL and
      DeltaBMI than the other two groups during long-term follow-up. On multivariate
      analyses, those who regained weight were more likely from socioeconomically
      advantaged neighborhoods (OR 1.82, CI 1.18-2.79). CONCLUSIONS: Several patient
      related characteristics predicted an increased likelihood of weight regain.
      Further studies are needed to elucidate how these factors contribute to weight
      recidivism following bariatric surgery.

PMID- 29067575
TI  - Inguinal hernia repair: is there a benefit to using the robot?
AB  - BACKGROUND: The number of robotic surgical procedures performed yearly is
      constantly rising, due to improved dexterity and visualization capabilities
      compared with conventional methods. We hypothesized that outcomes after robotic
      assisted inguinal hernia repair would not be significantly different from
      outcomes after laparoscopic or open repair. METHODS: All patients undergoing
      inguinal hernia repair between 2012 and 2016 were identified using institutional
      American College of Surgeons National Surgical Quality Improvement Program data.
      Demographics; preoperative, intraoperative, and postoperative characteristics;
      and outcomes were evaluated based on method of repair (Robot, Lap, or Open).
      Categorical variables were analyzed by Chi-square test and continuous variables
      using Mann-Whitney U. RESULTS: A total of 510 patients were identified who
      underwent unilateral inguinal hernia repair (Robot: 13.8% [n = 69], Lap: 48.1% [n
      = 241], Open: 38.1% [n = 191]). There were no demographic differences between
      groups other than age (Robot: 52 [39-62], Lap: 57 [45-67], and Open: 56 [48-67]
      years, p = 0.03). Operative duration was also different (Robot: 105 [76-146] vs.
      Lap: 81 [61-103] vs. Open: 71 [56-88] min, p < 0.001). There were no operative
      mortalities and all patients except one were discharged home the same day.
      Postoperative occurrences (adverse events, readmissions, and death) were similar
      between groups (Robot: 2.9% [2], Lap: 3.3% [8], Open: 5.2% [10], p = 0.53).
      Although rare, there was a significant difference in rate of postoperative skin
      and soft tissue infection (Robot: 2.9% [2] vs. Lap: 0% [0] vs. Open: 0.5% [1], p
      = 0.02). Cost was significantly different between groups (Robot: $7162 [$5942
      8375] vs. Lap: $4527 [$2310-6003] vs. Open: $4264 [$3277-5143], p < 0.001).
      CONCLUSIONS: Outcomes after robotic-assisted inguinal hernia repair were similar
      to outcomes after laparoscopic or open repair. Longer operative duration during
      robotic repair may contribute to higher rates of skin and soft tissue infection.
      Higher cost should be considered, along with surgeon comfort level and patient
      preference when deciding whether inguinal hernia repair is approached
      robotically.

PMID- 29067576
TI  - A new fluorescence imaging technique for visualizing hepatobiliary structures
      using sodium fluorescein: result of a preclinical study in a rat model.
AB  - BACKGROUND: Near-infrared fluorescence imaging has been recently applied in the
      field of hepatobiliary surgery. Our objective was to apply blue light
      fluorescence imaging to cholangiography and liver mapping during laparoscopic
      surgery. Therefore, we designed a preclinical study to evaluate the feasibility
      of using blue light fluorescence for cholangiography and liver mapping in a rat
      model. METHODS: Sodium fluorescein solution (1 mL to each individual) were
      administered intravenously to 20 male Sprague-Dawley rats (6 weeks old, 200-250
      g), after laparotomy. Whole abdominal organs were observed under blue light (at a
      wavelength of 440-490 nm) emitted from a commercialized LED curing light.
      RESULTS: Immediately after the tracer solution was administered into the
      circulatory system of the rat, it was possible to visualize the location of the
      kidneys and the bile duct under blue light emitted from the light source. The
      liver was vaguely stained green by the tracer, while the ureters were not. After
      establishing biliary retention via duct clamping in the left lateral segment of
      the liver, the green color of the segment became distinct by the tracer, which
      showed vague coloration following release of the clamp. CONCLUSION: We
      established the preclinical basis for using blue light fluorescence
      cholangiography and liver mapping in this study. The clinical feasibility of
      these techniques during laparoscopic cholecystectomy and hepatectomy remained to
      be demonstrated.

PMID- 29067577
TI  - Impact of hospital and surgeon case volume on morbidity in colorectal
      endometriosis management: a plea to define criteria for expert centers.
AB  - : National and international guidelines recommend referring patients with severe
      forms of endometriosis to expert centers. However, there is a lack of clear
      criteria to define an expert center. We examined the roles of surgeon and
      hospital procedure volumes as determinants of morbidity in deep infiltrating
      endometriosis of the rectum and sigmoid colon (DIERS). METHODS: We conducted a
      French retrospective multicenter study of hospital facilities performing
      colorectal surgery for DIERS in 2015. The primary end point was to analyze the
      relation between case volume and the incidence of complications. We estimated the
      optimal cut-off (OCO) determined by a minimal p-value approach. RESULTS: The
      study included 56 hospital facilities and collected data of 1135 cases of
      surgical management of colorectal endometriosis. The mean and median number of
      procedures per year and per surgeon were 9.17 and 5.58, respectively. The overall
      rate of grade III-V complication was 7.6% (82/1135). One grade V complication
      occurred. The rates of rectovaginal fistula, anastomotic leakage, pelvic abscess,
      and ureteral fistula were: 2.7% (31/1135), 0.79% (9/1135), 3.4% (39/1135), and
      0.70% (8/1135), respectively. An OCO of 20 procedures per center and per year (p
      < 0.001) was defined. The OCO per surgeon and per year varied between seven (p =
      0.007) and 13 procedures (p = 0.03). In a multivariate analysis, we found that
      only the volume of activity was independently correlated to complication outcomes
      (p = 0.0013). CONCLUSION: Our results contribute to providing objective morbidity
      data to determine criteria for defining expert centers for colorectal surgery for
      endometriosis.

PMID- 29067578
TI  - Transanal versus abdominal low rectal dissection for rectal cancer: long-term
      results of the Bordeaux' randomized trial.
AB  - AIM: The aim of the current study is to report long-term outcomes after transanal
      low rectal dissection compared with the conventional laparoscopic approach within
      the context of the Bordeaux' randomized trial. Results from this randomized trial
      have indicated that transanal approach was more effective than laparoscopic
      dissection regarding the rate of negative circumferential resection margin (CRM).
      Despite a high number of publications regarding the transanal approach for TME,
      there were no long-term data on survival and local recurrence which are now
      required. METHODS: One hundred patients with low rectal cancer suitable for
      laparoscopic TME with handsewn coloanal anastomosis were randomized in transanal
      versus laparoscopic low rectal dissection from 2008 to 2012. The randomization
      ratio was 1:1. All patients included in the trial were considered for long-term
      assessment. Local recurrence, overall- and disease-free survival were assessed by
      Kaplan-Meier and compared with Log-rank test. RESULTS: The follow up was 60.2
      months, similar in both group (p = 0.321). Overall, there were no differences of
      long-term outcomes. There was a significant association between CRM involvement
      and local recurrence (p = 0.011), however, the 5-year local recurrence rate was
      4%, without any significant difference between transanal and laparoscopic
      dissection: 3% vs. 5%; p = 0.300. The 5-year disease-free survival was 73%: 72%
      vs. 74; p = 0.351. CONCLUSION: Lower positivity of the circumferential resection
      margin was reported after transanal low rectal dissection, but it did not
      translate into a decreased incidence of local recurrence. Further investigations
      are necessary to demonstrate advantages of this new procedure.

PMID- 29067579
TI  - Trends in the Fundamentals of Laparoscopic Surgery(r) (FLS) certification exam
      over the past 9 years.
AB  - BACKGROUND: The Fundamentals of Laparoscopic Surgery(r) (FLS) certification exam
      assesses both cognitive and manual skills, and has been administered for over a
      decade. The purpose of this study is to report results over the past 9 years of
      testing in order to identify trends over time and evaluate the need to update
      scoring practices. This is a quality initiative of the SAGES FLS committee.
      METHODS: A representative sample of FLS exam data from 2008 to 2016 was analyzed.
      The de-identified data included demographics and scores for the cognitive and
      manual tests. Standard descriptive statistics were used to compare trends over
      the years, training levels, and to assess the pass/fail rate. RESULTS: A total of
      7232 FLS tests were analyzed [64% male, 6.4% junior (postgraduate year-PGY1-2),
      84% senior (PGY3-5), 2.8% fellows (PGY6), and 6.7% attending surgeons (PGY7)].
      Specialties included 93% general surgery (GS), 6.2% gynecology, and 0.9% urology.
      The Pearson correlation between cognitive and manual scores was 0.09. For the
      cognitive exam, there was an increase in scores over the years, and the most
      junior residents scored the lowest. For the manual skills, there were marginal
      differences in scores over the years, and junior residents scored the highest.
      The odds ratio of PGY3+ passing was 1.8 (CI 1.2-2.8) times higher than that of a
      PGY1-2. The internal consistency between tasks on the manual skills exam was
      0.73. If any one of the tasks was removed, the Cronbach's alpha dropped to
      between 0.65 and 0.71, depending on the task being removed. CONCLUSION: The
      cognitive and manual components of FLS test different aspects of laparoscopy and
      demonstrate evidence for reliability and validity. More experienced trainees have
      a higher likelihood of passing the exam and tend to perform better on the
      cognitive skills. Each component of the manual skills contributes to the exam and
      should continue to be part of the test.

PMID- 29067580
TI  - Comparison of laparoscopic to open pancreaticoduodenectomy in elderly patients
      with pancreatic adenocarcinoma.
AB  - INTRODUCTION: The purpose of the study is to compare perioperative and survival
      outcomes in elderly patients undergoing laparoscopic pancreaticoduodenectomy
      (LPD) to those undergoing open pancreaticoduodenectomy (OPD). METHODS: Patients
      aged >= 75 years with pancreatic adenocarcinoma undergoing LPD or OPD were
      identified from the NCDB (2010-2013). Baseline characteristics and perioperative
      outcomes were compared using a chi 2 and Student's t test. The Kaplan-Meier
      method was used to generate survival curves, and differences were tested using a
      log-rank test. A multivariate cox proportional hazard model was applied to
      estimate the hazard ratio (HR) of LPD on overall survival (OS). RESULTS: We
      identified 1768 patients aged >= 75 years who underwent LPD (n = 248, 14.0%) or
      OPD (n = 1520, 86.0%). The majority of patients in the LPD group had their
      surgery at facilities performing less than 5 LPDs per year (n = 165, 66.5%). 90
      day mortality was significantly lower in the LPD compared to the OPD (7.2 vs.
      12.2%, p = 0.049). The laparoscopic conversion rate was 30% (n = 74) and was
      associated with higher readmission rates (13.5 vs. 8.1%), 30-day mortality (8.0
      vs. 3.8%), and 90-day mortality (10.4 vs. 6.0%), but these did not reach
      statistical significance. Median OS was significantly longer in the LPD group
      (19.8 vs. 15.6 months, p = 0.022). After adjusting for patient and tumor-related
      characteristics, there was a trend towards improved survival in the LPD group (HR
      0.85, 95% CI 0.69-1.03). CONCLUSION: The vast majority of the NCDB participating
      facilities perform less than 5 LPD cases per year, which was associated with an
      increased risk of perioperative mortality. Overall 90-day mortality was
      significantly lower in the LPD group and there was a trend towards improved OS in
      the LPD group compared to the OPD group after adjusting for patient and tumor
      related characteristics. Studies with increased sample size and longer follow-up
      are needed before definitive conclusions can be made.

PMID- 29067581
TI  - Serial intermediate-term quality of life comparison after endoscopic submucosal
      dissection versus surgery in early gastric cancer patients.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC)
      is expected to provide better long-term health-related quality of life (HRQOL) by
      preserving the entire stomach. We aimed to compare serial changes in HRQOL
      characteristics between patients who underwent ESD versus surgery for EGC.
      METHODS: A gastric cancer patient cohort was prospectively enrolled from 2004 to
      2007. HRQOL of 161 EGC patients was prospectively assessed using the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 30 (EORTC-QLQ-C30) and the stomach cancer-specific module EORTC-QLQ-STO22 at
      baseline (i.e., diagnosis) and at 1, 6, 12, 18, and 24 months of post-treatment.
      RESULTS: Of 161 patients, 48 (29.8%) underwent ESD and 113 (70.2%) underwent
      surgery. HRQOL parameters of ESD patients were similar to or better than baseline
      values. At 1-month post-treatment, the surgery group had significantly poorer
      scores than the ESD group (P < 0.05) for factors except emotional and cognitive
      functioning, financial problems, anxiety, and hair loss. However, most of the
      HRQOL parameters in the surgery group improved during the first post-treatment
      year, with between-group differences becoming insignificant. Only five parameters
      (physical functioning, eating restriction, dysphagia, diarrhea, and body image)
      remained significantly better in the ESD group than the surgery group for > 1
      year post-treatment (P < 0.05). The surgery group had significantly higher
      treatment-associated complications than the ESD group (15.0 vs. 2.1%; P = 0.017).
      The overall survival was not different between the both groups (5-year overall
      survival rates, 97.7% in the ESD group vs. 99.1% in the surgery group; P = 0.106
      by the log-rank test). CONCLUSION: Compared with surgery, ESD can provide better
      HRQOL benefits for EGC patients, especially during the early post-treatment
      period. However, surgical treatment should not be rejected only due to the
      concern about HRQOL impairments because most of them improved during follow-up
      periods.

PMID- 29067582
TI  - Growth in robotic-assisted procedures is from conversion of laparoscopic
      procedures and not from open surgeons' conversion: a study of trends and costs.
AB  - BACKGROUND: Utilization of laparoscopy (LAP) has been increasing in general
      surgery for years, and there is currently a rapid increase in the utilization of
      robotic-assisted surgeries (RAS). This study evaluates trends in the surgical
      approach utilized in some commonly performed surgeries, the proportion of each
      approach within the procedures, and the cost of these surgeries based on the
      surgical approach. METHODS: This is a retrospective study using the Vizient
      database. The database was queried using ICD-9 codes for colectomy,
      cholecystectomy, inguinal and ventral hernia repairs, and bariatric surgeries,
      either open, LAP, or robotically performed. Utilization trends were evaluated
      between quarters, over a 7-year period, and direct cost was compared between
      approaches. IBM SPSS v.23.0.0 was used for data analysis, with alpha = 0.05.
      RESULTS: 857,468 patients underwent colectomy, cholecystectomy, inguinal and
      ventral hernia repairs, and bariatric procedures. A significant decrease in open
      approach utilization was seen in colectomy (71.8-61.9%), cholecystectomy (35.7
      27.1%), and bariatric surgeries (20.1-10.1%), whereas both LAP and RAS
      utilization increased (p < 0.001). Significant RAS increase was seen in all five
      procedures: colectomy (0.4-8.0%), cholecystectomy (0.2-1.8%), IHR (19.9-29.4%),
      VHR (0.2-2.9%), and bariatric (0.6-5.4%), compared to a decrease in LAP (p <
      0.001). Surgery cost was significantly higher for open ($14,364), followed by RAS
      ($11,376) and LAP ($7945), p < 0.001. CONCLUSIONS: Robotic technology is commonly
      viewed as enabling open procedures to be converted to minimally invasive, a trend
      not observed in our study. Our trends analysis revealed significant RAS
      utilization increase from LAP procedures and not from open procedure conversion,
      although specific surgeon data were not available. RAS were costlier than LAP for
      all five procedures. The benefits of rapid robot adoption and the forces that are
      driving these must be examined against a backdrop of burdening an already
      expensive healthcare system.

PMID- 29067583
TI  - Feasibility of real-time intestinal bloodstream evaluation using probe-based
      confocal laser endomicroscopy in a porcine intestinal ischemia model.
AB  - BACKGROUND: Intestinal ischemia can lead to fatal complications if left
      unrecognized during surgery. The current techniques of intraoperative
      microvascular assessment remain subjective. Probe-based confocal laser
      endomicroscopy (pCLE) has the potential to objectively evaluate microvascular
      blood flow in real-time setting. The present study evaluated the technical
      feasibility of real-time intestinal bloodstream evaluation using pCLE in a
      porcine intestinal ischemia model. METHODS: Seven pigs were used. The intestinal
      ischemia model was prepared by sequentially dividing the mesenteric blood
      vessels. The intestinal bloodstream was evaluated on its serosal surface using
      pCLE (Cellvizio 488 probe, Ultra Mini O) at every 1-cm segment from a vessel
      preservation border (i.e., the cut end of the vessel). Images of the blood
      vessels and flow of red blood cells (RBCs) in each visualized vessel were semi
      qualitatively assessed using a 3-scale scoring system. In addition, 25 surgeons
      blindly assessed the 10 movies recorded at 0, 1, 2, 3, and 5 cm from a vessel
      preservation border using a 4-scale scoring system to confirm the consistency of
      the evaluation of the pCLE system. RESULTS: Images of the blood vessels were
      successfully obtained from the cut end of the vessel to the segment 4 cm away.
      Good unidirectional flow of RBCs was observed from the cut end to the 2-cm
      segment, whereas the flow became bidirectional between 2 and 3 cm segments.
      Beyond 4 cm, no flow images were obtained. The specimen obtained from the segment
      beyond 4 cm showed remarkable mucosal color change, which was confirmed as a
      necrotic change histologically. The evaluations from the cut end of the vessel to
      the segment 1 cm away by surgeons were excellent or good and it was almost
      consistent. CONCLUSIONS: Real-time bloodstream evaluation using pCLE is feasible
      and potentially effective for predicting intestinal ischemia during surgery.

PMID- 29067584
TI  - Impact of surgical approach on perioperative and long-term outcomes following
      esophagectomy for esophageal cancer.
AB  - BACKGROUND: Surgical resection remains a critical component of esophageal cancer
      treatment with curative-intent. The aim of this study was to compare open (OE) to
      minimally invasive Ivor Lewis esophagectomy (MIE) with respect to perioperative
      and oncologic outcomes. METHODS: Retrospective single-institution review of MIE
      and OE patients operated between 2001 and 2015 was conducted. Univariable and
      multivariable models were created using Cox regression. The Kaplan-Meier method
      was used to compare oncologic outcomes. Propensity score matching was used to
      compare oncological outcomes in MIE and OE patients. RESULTS: Of 210 esophageal
      resection patients, 47% had OE (137/291) and 25% had MIE (73/291). The MIE and OE
      groups were comparable with respect to patient factors and operative details.
      Fewer OE patients received neoadjuvant chemoradiation. MIE was associated with
      improved lymph node yield, (MIE = 30 [IQR:22-39]; OE = 14 [IQR:7-19], p < 0.001),
      less intraoperative blood loss (MIE = 312 mL [100-400]; OE = 657 mL [350-700], p
      < 0.001), and shorter median length of stay (MIE = 10 days [IQR = 8-14]; OE = 14
      days [IQR = 11-22] p < 0.01). The OE group had significantly more adverse events
      resulting in reoperation or intensive care unit admission (MIE = 21%; OE = 34%; p
      < 0.01). On multivariable analysis, age and positive resection margins were
      associated with decreased odds of survival. The number of lymph nodes retrieved,
      positive resection margins, and pathologic stage were significant predictors of
      disease-free survival. Analysis of 69 matched pairs showed equivalent median
      overall survival (MIE = 49 months [18-67]; OE = 29 months [17-69]; p = 0.26) and
      disease-free survival (MIE = 9 [6-22]; OE = 13 [6-22]; p = 0.45) between the two
      groups. CONCLUSIONS: Although long-term oncologic outcomes appear to be similar,
      MIE is associated with significantly less intraoperative blood loss, improved
      lymph node yield, less risk of severe postoperative adverse events, and shorter
      length of stay.

PMID- 29067585
TI  - Intrinsic Response Towards Physiologic Stiffness is Cell-Type Dependent.
AB  - In the continuous search for better tissue engineering scaffolds it has become
      increasingly clear that the substrate properties dramatically affect cell
      responses. Here we compared cells from a physiologically stiff tissue, melanoma,
      to cells isolated from a physiologically soft tissue, brain. We measured the cell
      line responses to laminin immobilized onto glass or polyacrylamide hydrogels
      tuned to have a Young's modulus ranging from 1 to 390 kPa. Single cells were
      analyzed for spreading area, shape, total actin content, actin-based
      morphological features and modification of immobilized laminin. Both cell types
      exhibited stiffness- and laminin concentration-dependent responses on
      polyacrylamide and glass. Melanoma cells exhibited very little spreading and were
      rounded on soft (1, 5, and 15 kPa) hydrogels while cells on stiff (40, 100, and
      390 kPa) hydrogels were spread and had a polarized cell shape with large
      lamellipodia. On rigid glass surfaces, spreading and actin-based morphological
      features were not observed until laminin concentration was much higher.
      Similarly, increased microglia cell spreading and presence of actin-based
      structures were observed on stiff hydrogels. However, responses on rigid glass
      surfaces were much different. Microglia cells had large spreading areas and
      elongated shapes on glass compared to hydrogels even when immobilized laminin
      density was consistent on all gels. While cell spreading and shape varied with
      Young's modulus of the hydrogel, the concentration of f-actin was constant. A
      decrease in laminin immunofluorescence was associated with melanoma and microglia
      cell spreading on glass with high coating concentration of laminin, indicating
      modification of immobilized laminin triggered by supraphysiologic stiffness and
      high ligand density. These results suggest that some cell lines are more
      sensitive to mechanical properties matching their native tissue environment while
      other cell lines may require stiffness and extracellular ligand density well
      above physiologic tissue before saturation in cell spreading, elongation and
      cytoskeletal re-organization are reached.

PMID- 29067586
TI  - Psoriatic arthritis: is it time to treat-to-target or target to treat?
AB  - Treat-to-target recommendations provide physicians a useful strategy to reduce
      the probability of disease progression and in general to manage PsA patients.
      However, it could be difficult to apply in real life, since PsA is a very
      heterogeneous disease with different manifestations to be treated. In fact,
      depending on the patient's expectation, some aspects of the disease could be
      prominent or not, beyond the mere achievement of the target of remission or low
      disease activity. In this context, the concept of a "target to treat" strategy
      should be taken in to account.

PMID- 29067587
TI  - Altered frequencies of memory B cells in new-onset systemic lupus erythematosus
      patients.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease,
      characterized by B cell hyperactivity and pathogenic autoantibodies formation.
      The objective of this study is to evaluate the distribution of B cell subsets in
      patients with SLE. We included patients with SLE followed in First Affiliated
      Hospital of Xi'an JiaoTong University, Xi'an, China. Flow cytometry was used to
      measure frequencies of B cell subsets, including memory B cells, switched memory
      B cells, non-switched memory B cells, double-negative memory B cells, and naive B
      cells in 130 patients with SLE and 55 healthy controls. The different
      distributions of B cell subsets were further evaluated by their associations with
      disease activity and clinical manifestation. SLE patients showed significant
      alteration of B cell subsets, including lower frequency of non-switched memory B
      cells and higher double-negative memory B cells. The frequencies of B cell
      subsets also varied between new-onset SLE patients and chronic SLE patients.
      Frequencies of total memory B cells, switched memory B cells, and non-switched
      memory B cells were lower in new-onset SLE patients and frequency of naive B
      cells was higher compared with healthy controls. Chronic SLE patients showed
      increased switched memory B cells and double-negative memory B cells. In
      addition, switched memory B cells and double-negative B cells were higher in
      patients with lupus nephritis (LN) regardless of disease activity. Our findings
      suggested that abnormalities of the B cell subsets homeostasis might contribute
      to the pathogenesis of SLE.

PMID- 29067588
TI  - A Model of Family and Child Functioning in Siblings of Youth with Autism Spectrum
      Disorder.
AB  - The potential clinical needs of typically developing (TD) siblings of youth with
      autism spectrum disorder (ASD) remain disputed. A total of 239 mothers of youth
      aged 6-17, including one youth with ASD (M = 11.14 years; simplex families) and
      at least one other youth (M = 11.74 years) completed online standardized measures
      of various familial factors and TD youth outcomes. Overall, only 6-23% of
      siblings were identified within the clinical range of emotional, behavioral, or
      social functioning. Both maternal depression and sibling relationship were
      identified as key pathways in predicting siblings' functioning within a good
      fitting path analysis model. The current model is presented as a novel base for
      the development of future research and services for this unique population of
      children.

PMID- 29067589
TI  - Income inequality and subjective well-being: a systematic review and meta
      analysis.
AB  - BACKGROUND: Reducing income inequality is one possible approach to boost
      subjective well-being (SWB). Nevertheless, previous studies have reported
      positive, null and negative associations between income inequality and SWB.
      OBJECTIVES: This study reports the first systematic review and meta-analysis of
      the relationship between income inequality and SWB, and seeks to understand the
      heterogeneity in the literature. METHODS: This systematic review was conducted
      according to guidance (PRISMA and Cochrane Handbook) and searches (between
      January 1980 and October 2017) were carried out using Web of Science, Medline,
      Embase and PsycINFO databases. RESULTS: Thirty-nine studies were included in the
      review, but poor data reporting meant that only 24 studies were included in the
      meta-analysis. The narrative analysis of 39 studies found negative, positive and
      null associations between income inequality and SWB. The meta-analysis confirmed
      these findings. The overall association between income inequality and SWB was
      almost zero and not statistically significant (pooled r = - 0.01, 95% CI - 0.08
      to 0.06; Q = 563.10, I 2 = 95.74%, p < 0.001), suggesting no association between
      income inequality and SWB. Subgroup analyses showed that the association between
      income inequality and SWB was moderated by the country economic development (i.e.
      developed countries: r = - 0.06, 95% CI -0.10 to -0.02 versus developing
      countries: r = 0.16, 95% CI 0.09-0.23). The association between income inequality
      and SWB was not influenced by: (a) the measure used to assess SWB, (b) geographic
      region, or (c) the way in which income inequality was operationalised.
      CONCLUSIONS: The association between income inequality and SWB is weak, complex
      and moderated by the country economic development.

PMID- 29067590
TI  - Within-person fluctuations in wellbeing and task-specific work ability.
AB  - PURPOSE: To research within-person fluctuations in occupational health, work
      ability and wellbeing, we need new measurement strategies. We studied absolute
      agreement for weekly measurements of task-specific work ability and relationships
      between wellbeing, work demands and personal factors and task-specific work
      ability over time. METHODS: Forty-eight Dutch academic researchers answered
      questions during 12 consecutive weeks. Physical and mental work demands,
      indicators of wellbeing and task-specific work ability in each week were
      measured. Intra-class correlation coefficients (ICC) for absolute agreement
      between task-specific work ability measures were calculated. For application in
      individual workers, an ICC > 0.90 was regarded as suitable. Multilevel models
      were used to relate both time-invariant and time-varying predictors to task
      specific work ability. RESULTS: Multiple measurements increased the reliability.
      Absolute agreement, however, did not reach the optimal level, except for the task
      'ability to conduct data analyses' which had an ICC value of 0.95 (95% CI 0.91
      0.98). Individuals' leisure time physical activity (p = 0.03) and relational (p =
      0.02) and social (p = 0.02) wellbeing were related to their average task-specific
      work ability. Weekly physical demands (p = 0.01) and personal (p = 0.04) and
      general wellbeing (p = 0.03) were related to weekly fluctuations in work ability.
      CONCLUSIONS: We demonstrated intra-individual variability in repeated assessments
      of task-specific work ability, pointing to the need for multiple measurements
      when characterizing work ability. The finding that some time-invariant and time
      varying predictors can be related to the estimate of aspects of task-specific
      work ability and its fluctuations is helpful in understanding the dynamics of
      this concept.

PMID- 29067591
TI  - Nanoparticulate Impurities Isolated from Pharmaceutical-Grade Sucrose Are a
      Potential Threat to Protein Stability.
AB  - PURPOSE: To investigate the effect of nanoparticulate impurities (NPIs) isolated
      from pharmaceutical-grade sucrose, on the stability of monoclonal antibodies
      (mAbs). METHODS: NPIs were purified from pharmaceutical-grade sucrose and spiked
      into trastuzumab, rituximab, infliximab, and cetuximab formulations. The
      stability of the mAbs as a function of storage time, temperature, and NPI
      concentration was assessed by visual inspection, flow-imaging microscopy,
      nanoparticle tracking analysis, size-exclusion chromatography, capillary
      isoelectric focusing, and intrinsic differential scanning fluorimetry. RESULTS:
      NPIs negatively affected the stability of all mAbs, albeit it to different
      extents. After spiking with NPIs, trastuzumab formulations showed high numbers of
      MUm-sized particles and turbidity, rituximab and cetuximab formulations contained
      high numbers of nm-sized particles, while infliximab formed nm- and MUm-sized
      particles, and showed turbidity. Low-molecular-weight species were observed for
      rituximab and infliximab, whereas high-molecular-weight species were detected for
      cetuximab. Whereas the stability of trastuzumab and infliximab formulations was
      affected directly after spiking NPIs, degradation of rituximab and cetuximab was
      observed only after 14 weeks at elevated temperatures. Moreover, the stability of
      rituximab and infliximab was affected by NPI concentrations that are potentially
      present in final drug products. CONCLUSIONS: The presence of sucrose-derived NPIs
      in (bio-)pharmaceutical formulations may pose a threat to the stability of mAbs.

PMID- 29067592
TI  - Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium
      Chloride from Ocular Formulations.
AB  - PURPOSE: About 70% of eye drops contain benzalkonium chloride (BAK) to maintain
      sterility. BAK is an effective preservative but it can cause irritation and
      toxicity. We propose to mitigate ocular toxicity without compromising sterility
      by incorporating a filter into an eye drop bottle to selectively remove BAK
      during the process of drop instillation. METHODS: The filter is a packed bed of
      particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common
      ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated
      trimethylolpropane triacrylate as crosslinker can be incorporated into a modified
      eyedrop bottle tip to selectively remove the preservative as the formulation is
      squeezed out of the bottle. Hydraulic permeability of the plug is measured to
      determine the resistance to eye drop squeezing, and % removal of BAK and drugs
      are determined. RESULTS: The modified tip has a hydraulic permeability of about 2
      Darcy, which allows eyedrops formulations to flow through without excessive
      resistance. The tip is designed such that the patients can create an eyedrop of
      solution of 1-10 cP viscosity in 4 s with a nominal pressure. During this short
      contact time, the packed particles removed nearly 100% of benzalkonium chloride
      (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the
      concentration of contained active components. CONCLUSION: Our novel design can
      eliminate the preservative induced toxicity from eye drops thereby impacting
      hundreds of millions of patients with chronic ophthalmic diseases like glaucoma
      and dry eyes.

PMID- 29067593
TI  - JSH guideline for tumors of hematopoietic and lymphoid tissues-leukemia: 3. Acute
      lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL).

PMID- 29067594
TI  - Genetic variation of Kruppel-like factor 1 (KLF1) and fetal hemoglobin (HbF)
      levels in beta0-thalassemia/HbE disease.
AB  - Heterogeneity of HbF levels in beta0-thalassemia/HbE disease has been reported to
      be associated with variations in clinical manifestations of the disease, and
      several genetic-modifying factors beyond the beta-globin gene cluster have been
      identified as HbF regulators. Down-regulation or heterozygous mutations of
      Kruppel-like factor 1 (KLF1) is associated with elevated HbF levels in non
      thalassemia subjects. This study confirms that experimental down-regulation of
      KLF1 in beta0-thalassemia/HbE-derived erythroblasts significantly increases HbF
      production (up to 52.3 +/- 2.4%), albeit with slightly delayed erythroid terminal
      differentiation. KLF1 exome sequencing of 130 Thai beta0-thalassemia/HbE patients
      without co-inheritance of alpha-thalassemia found six patients with KLF1
      heterozygous mutations including rs2072596 (p.F182L; n = 5) and rs745347362
      (p.P284L; n = 1) missense mutations. However, while these patients had high HbF
      levels (38.1 +/- 7.5%), they were all associated with a severe clinical
      phenotype. These results suggest that while reduction of KLF1 expression in beta0
      thalassemia/HbE erythroblasts can increase HbF levels, it is not sufficient to
      alleviate the clinical phenotype.

PMID- 29067595
TI  - Comparison on Anticoagulation and Antiplatelet Aggregation Effects of Puerarin
      with Heparin Sodium and Tirofiban Hydrochloride: An In Vitro Study.
AB  - OBJECTIVE: To detect the anticoagulation and antiplatelet effects of different
      concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the
      blood samples of healthy volunteers by Sonoclot coagulation and platelet function
      analyzer. METHODS: Peripheral blood samples were extracted from 20 healthy
      volunteers, followed by adding different concentrations of puerarin, heparin
      sodium and tirofiban hydrochloride. Samples were detected for activated clotting
      time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and
      platelet function analyzer instrument. RESULTS: For puerarin and heparin sodium,
      the values of ACT gradually increased, and the values of CR and PF gradually
      decreased with increasing in drug concentration. There was a linear (or log
      linear) relationship between ACT, CR, PF value and drug concentration (P<0.01).
      Corresponding to each value, a regression equation was obtained. For tirofiban
      hydrochloride, the values of ACT and CR had no significant changes, while PF
      values gradually decreased with concentration increasing. There was also a linear
      relationship between PF values and concentrations of tirofiban hydrochloride
      (P<0.01). Under the same ACT values, the puerarin corresponding CR values (CR = e
      0.0062ACT+4.31, P<2.2e-16) were always higher than the corresponding values (CR =
      e-0.0028ACT+2.79, P-value<2.2e-16) of heparin sodium. For high concentrations of
      puerarin (e.g. 3.8 mg/600 MUL) and tirofiban hydrochloride (e.g. 0.8 MUg/600
      MUL), PF values had no significant difference. However, PF values for high
      puerarin concentration had a larger variance. CONCLUSIONS: Puerarin has similar
      anticoagulant and antiplatelet effects with the heparin sodium, and may have a
      lower hemorrhage risk than heparin sodium when obtained the same anticoagulation
      effect in the concentration range of this experiment. In addition, for high
      concentration, puerarin had the same antiplatelet function as tirofiban
      hydrochloride but with a larger individual variability.

PMID- 29067597
TI  - Factors influencing health-related quality of life after gastrectomy for cancer.
AB  - AIM: Insight in health-related quality of life (HRQoL) may improve clinical
      decision making and inform patients about the long-term effects of gastrectomy.
      This study aimed to evaluate and identify factors associated with HRQoL after
      gastrectomy. METHODS: This cross-sectional study used prospective databases from
      seven Dutch centers (2001-2015) including patients who underwent gastrectomy for
      cancer. Between July 2015 and November 2016, European Organization for Research
      and Treatment of Cancer HRQoL questionnaires QLQ-C30 and QLQ-STO22 were sent to
      all surviving patients without recurrence. The QLQ-C30 scores were compared to a
      Dutch reference population using a one-sample t test. Spearman's rank test was
      used to correlate time after surgery to HRQoL, and multivariable linear
      regression was performed to identify factors associated with HRQoL. RESULTS: A
      total of 222 of 274 (81.0%) patients completed the questionnaires. Median follow
      up was 29 months (range, 3-171) and 86.9% of patients had a follow-up >1 year.
      The majority of patients had undergone neoadjuvant treatment (64.4%) and total
      gastrectomy (52.7%). Minimally invasive gastrectomy (MIG) was performed in 50% of
      the patients. Compared to the general population, gastrectomy patients scored
      significantly worse on most functional and symptom scales (p < 0.001) and
      slightly worse on global HRQoL (78 vs. 74, p = 0.012). Time elapsed since surgery
      did not correlate with global HRQoL (Spearman's rho = 0.06, p = 0.384). Distal
      gastrectomy, neoadjuvant treatment, and MIG were associated with better HRQoL (p
      < 0.050). CONCLUSION: After gastrectomy, patients encounter functional
      impairments and symptoms, but experience only a slightly impaired global HRQoL.
      Distal gastrectomy, the ability to receive neoadjuvant treatment, and MIG may be
      associated with HRQoL benefits.

PMID- 29067598
TI  - Religious versus Conventional Internet-based Cognitive Behavioral Therapy for
      Depression.
AB  - The accessibility and efficacy of two Internet-supported interventions for
      depression: conventional cognitive behavioral therapy (C-CBT) and religious CBT
      (R-CBT) were investigated. Depressed participants (N = 79) were randomly assigned
      to either active treatment or wait-listed control group. Self-report measures of
      depression, anxiety, and life quality were collected before, immediately after,
      and 6 months after the intervention. Significant differences among the three
      conditions emerged at post-intervention with medium to large effect sizes
      (Cohen's d between 0.45 and 1.89), but no differences between the R-CBT and C-CBT
      were found. However, the addition of religious components to CBT contributed to
      the initial treatment appeal for religious participants, thus increasing the
      treatment accessibility.

PMID- 29067599
TI  - Legislative Enforcement of Nonconsensual Determination of Neurological (Brain)
      Death in Muslim Patients: A Violation of Religious Rights.
AB  - Death is defined in the Quran with a single criterion of irreversible separation
      of the ruh (soul) from the body. The Quran is a revelation from God to man, and
      the primary source of Islamic knowledge. The secular concept of death by
      neurological criteria, or brain death, is at odds with the Quranic definition of
      death. The validity of this secular concept has been contested scientifically and
      philosophically. To legitimize brain death for the purpose of organ donation and
      transplantation in Muslim communities, Chamsi-Pasha and Albar (concurring with
      the US President's Council on Bioethics) have argued that irreversible loss of
      capacity for consciousness and breathing (apneic coma) in brain death defines
      true death in accordance with Islamic sources. They have postulated that the
      absence of nafs (personhood) and nafas (breath) in apneic coma constitutes true
      death because of departure of the soul (ruh) from the body. They have also
      asserted that general anesthesia is routine in brain death before surgical
      procurement. Their argument is open to criticism because: (1) the ruh is
      described as the essence of life, whereas the nafs and nafas are merely human
      attributes; (2) unlike true death, the ruh is still present even with absent nafs
      and nafas in apneic coma; and (3) the routine use of general anesthesia indicates
      the potential harm to brain-dead donors from surgical procurement. Postmortem
      general anesthesia is not required for autopsy. Therefore, the conclusion must be
      that legislative enforcement of nonconsensual determination of neurological
      (brain) death and termination of life-support and medical treatment violates the
      religious rights of observant Muslims.

PMID- 29067600
TI  - Reduced Port Laparoscopic Distal Gastrectomy with D2 Lymphadenectomy.
AB  - BACKGROUND: Reduced port laparoscopic surgery (RPLS), as a more minimally
      invasive treatment alternative to conventional laparoscopic surgery (CLS), has
      been increasing in recent years. 1 With the accumulation of surgical experience
      and improvements in surgical techniques, the indication of RPLS has been
      gradually extended from benign diseases to malignant tumors, including gastric
      cancer. 2-4 However, due to the lack of counteraction and triangulation,
      lymphadenectomy during reduced port laparoscopic gastrectomy (RPLG) for gastric
      cancer was considered challenging. In this study, we report our experience
      performing RPLG with D2 lymphadenectomy for distal gastric cancer. METHODS: A
      disposable, single-incision, multiport, laparoscopic surgery trocar was used
      through a 3-cm incision at the umbilicus for the laparoscopist and surgeon's
      right hand. One 12-mm trocar was inserted at the upper-right quadrant for the
      surgeon's left hand. Distal gastrectomy with D2 lymphadenectomy was performed in
      the same manner with CLS. 5 After extracting the resected specimen through the
      umbilicus incision, intracorporeal Roux-en-Y or B-II gastrojejunostomy was used
      for reconstruction. RESULTS: RPLG with D2 lymphadenectomy was performed on five
      patients from April 2017 to June 2017. No intraoperative event requiring
      conversion to CLS or open surgery occurred. No postoperative complication was
      observed. The median operating time and blood loss was 166 min and 50 ml. The
      mean number of retrieved lymph nodes was 32.7. Postoperatively, the mean time to
      first flatus, soft intake, and hospital stay was 2.6, 3.5, and 6.7 days
      respectively. CONCLUSIONS: RPLG with D2 lymphadenectomy might be safe and
      feasible in selected patients.

PMID- 29067601
TI  - Do Lumpectomy Cavity Shaved Margins Really Not Impact Re-excision Rates in Breast
      Cancer?

PMID- 29067602
TI  - Prophylactic Cholecystectomy at Time of Surgery for Small Bowel Neuroendocrine
      Tumor Does Not Increase Postoperative Morbidity.
AB  - BACKGROUND: Prophylactic cholecystectomy at time of surgery for small bowel
      neuroendocrine tumor (SBNET) has been advocated, as these patients often go on to
      require somatostatin analogue therapy, which is known to increase risk of
      cholestasis and associated complications. Little is known regarding patterns of
      adoption of this practice or its associated morbidity. METHODS: The American
      College of Surgeons National Surgical Quality Improvement Program database (2008
      2014) was queried to identify patients who underwent SBNET resection. The risk
      differences of morbidity and mortality associated with performance of concurrent
      cholecystectomy were determined with multivariable adjustment for confounders.
      RESULTS: Among 1300 patients who underwent SBNET resection, 144 (11.1%) underwent
      concurrent cholecystectomy. Median age of patients undergoing cholecystectomy was
      62 years [interquartile range (IQR) 52-69 years], and 75 were male. They more
      commonly had disseminated cancer (36.1 vs. 11.6%, p < 0.001) or SBNET located in
      duodenum (10.4 vs. 4.9%, p = 0.045) without difference in other baseline
      characteristics. Operative time was significantly longer in the cholecystectomy
      group (median 172 vs. 123 min, p < 0.001). Rate of postoperative morbidity was
      not significantly different between cholecystectomy and no-cholecystectomy groups
      (11.8 vs. 11.1%, p = 0.79). After adjustment for confounding, the risk difference
      of morbidity attributable to cholecystectomy was + 0.4% [95% confidence interval
      (CI) - 4.9 to + 5.6%]. Mortality within 30 days was not significantly different
      between cholecystectomy and no-cholecystectomy groups (1.4 vs. 0.6%, p = 0.29).
      CONCLUSIONS: Concurrent cholecystectomy at time of resection of SBNET is not
      associated with higher morbidity or mortality yet is performed in a minority of
      patients. Prospective study can identify which patients may derive benefit from
      this approach.

PMID- 29067603
TI  - Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive
      Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.
AB  - BACKGROUND AND PURPOSE: Approximately 20% of melanoma patients harbor metastases
      in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and
      recent evidence questions the therapeutic benefit of completion lymph node
      dissection (CLND). We built a nomogram for prediction of NSN status in melanoma
      patients with positive SNB. METHODS: Data on anthropometric and
      clinicopathological features of patients with cutaneous melanoma who underwent
      CLND after a positive SNB were collected from nine Italian centers. Multivariate
      logistic regression was utilized to identify predictors of NSN status in a
      training set, while model efficiency was validated in a validation set. RESULTS:
      Data were available for 1220 patients treated from 2000 through 2016. In the
      training set (n = 810), the risk of NSN involvement was higher when (1) the
      primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer
      nodes are excised and (4) more nodes are involved; and (5) the lymph node
      metastasis is larger or (6) is deeply located. The model showed high
      discrimination (area under the receiver operating characteristic curve 0.74, 95%
      confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI
      0.15-0.17) performance in the validation set (n = 410). The nomogram including
      these six clinicopathological variables performed significantly better than five
      other previously published models in terms of both discrimination and
      calibration. CONCLUSIONS: Our nomogram could be useful for follow-up
      personalization in clinical practice, and for patient risk stratification while
      conducting clinical trials or analyzing their results.

PMID- 29067604
TI  - Partial Verification Distorts Estimates of Sensitivity in Diagnostic Accuracy
      Studies for Fine-Needle Aspiration Cytology.

PMID- 29067605
TI  - Surgical Management of Primary Retroperitoneal Sarcomas: Rationale for Selective
      Organ Resection.
AB  - BACKGROUND: Recently, some have argued for routine resection of adjacent but
      uninvolved organs in patients with retroperitoneal sarcoma (RPS) without
      stipulating the rationale for such organ resection (beyond the need to achieve a
      macroscopically complete resection) or examining histopathologic organ invasion
      (HOI). This study reviewed the authors' experience with primary RPS to
      investigate the rate and rationale for individual organ resection and the rate of
      HOI. METHODS: Operative and pathology reports for patients with primary RPS who
      underwent resection at our institution were retrospectively reviewed.
      Histopathologic organ invasion was confirmed by a dedicated sarcoma pathologist.
      RESULTS: From 2002 through 2011, 118 patients underwent resection of a primary
      RPS, and 99 of these patients (84%) had at least one organ resected. Kidney (n =
      57), colon (n = 51), and adrenal (n = 41) were the most commonly resected organs.
      For the 302 organs removed, the perioperative clinical rationale for the
      resection was suspected invasion or tumor origin (n = 52, 17%), involved end
      organ vasculature (n = 39, 13%), organ encasement (n = 42, 14%), tumor adherence
      (n = 127, 42%), resection required for R0/R1 resection (n = 25, 8%), or other (n
      = 17, 6%). The presence of HOI was found in 77 (25%) of the 302 organs resected.
      In the reviewed studies, HOI was identified in 34 (65%) of 52 organs suspected of
      invasion or tumor origin, in 19% of organs resected due to tumor encasement, and
      in 26% of organs with adherent tumor, even when not suspected intraoperatively,
      but was never identified in organs resected purely as part of a liberal en bloc
      resection of adjacent organs. When invasion was suspected intraoperatively, HOI
      was confirmed in 50, 78, and 100% of resected organs respectively for well
      dedifferentiated liposarcoma, dedifferentiated liposarcoma (DDLPS), and
      leiomyosarcoma (LMS). CONCLUSIONS: Histologic organ invasion was observed more
      commonly in organs resected with suspicion of invasion than in organs resected
      simply to achieve a negative margin, although this reflects a degree of
      subjectivity and selection bias. In more than one-fourth of adherent organs, HOI
      was present even when not suspected intraoperatively. Histologic subtype may
      predict HOI because DDLPS and LMS are associated with high rates of HOI when
      invasion is suspected intraoperatively. Development of a data-driven, histology
      specific rationale for adjacent organ resection is critical.

PMID- 29067606
TI  - A novel homozygous 1-bp deletion in the NOBOX gene in two Brazilian sisters with
      primary ovarian failure.
AB  - PURPOSE: Primary ovarian failure (POF) is characterized by amenorrhea,
      hypoestrogenism, and elevated gonadotropin levels in women leading to infertility
      under the age of 40 years. POF is a heterogeneous disease with different causes,
      and several genes have been associated with the POF phenotype. Thus, Whole-exome
      sequencing (WES) was performed in a consanguineous family with two sisters
      affected by POF. METHODS: All exons of both sisters were massively sequenced by
      WES, and the segregation was confirmed by Sanger sequencing. RESULTS: The novel
      homozygous c.1489delT variant in the NOBOX gene was identified in the two sisters
      with POF. Their parents were heterozygous carriers of this variant and,
      therefore, consistent with an autosomal recessive mode of inheritance. The
      c.1489delT NOBOX variant has not been previously reported in any public available
      databases (1000Genomes, 6500ESP/EVS, ExAC, and gnomAD). Furthermore, this variant
      was neither present in 387 Brazilian exomes control individuals nor in 200
      fertile Brazilian women screened by Sanger sequencing. CONCLUSION: We report the
      first familial case of a novel homozygous NOBOX variant with an autosomal
      recessive mode of inheritance, thus allowing for a genetic diagnosis of primary
      ovarian failure.

PMID- 29067607
TI  - Physiological serum 25-hydroxyvitamin D concentrations are associated with
      improved thyroid function-observations from a community-based program.
AB  - PURPOSE: Vitamin D deficiency has been associated with an increased risk of
      hypothyroidism and autoimmune thyroid disease. Our aim was to investigate the
      influence of vitamin D supplementation on thyroid function and anti-thyroid
      antibody levels. METHODS: We constructed a database that included 11,017
      participants in a health and wellness program that provided vitamin D
      supplementation to target physiological serum 25-hydroxyvitmain D [25(OH)D]
      concentrations (>100 nmol/L). Participant measures were compared between entry to
      the program (baseline) and follow-up (12 +/- 3 months later) using an intent-to
      treat analysis. Further, a nested case-control design was utilized to examine
      differences in thyroid function over 1 year in hypothyroid individuals and
      euthyroid controls. RESULTS: More than 72% of participants achieved serum 25(OH)D
      concentrations >100 nmol/L at follow-up, with 20% above 125 nmol/L.
      Hypothyroidism was detected in 2% (23% including subclinical hypothyroidism) of
      participants at baseline and 0.4% (or 6% with subclinical) at follow-up. Serum
      25(OH)D concentrations >=125 nmol/L were associated with a 30% reduced risk of
      hypothyroidism and a 32% reduced risk of elevated anti-thyroid antibodies.
      Hypothyroid cases were found to have higher mean serum 25(OH)D concentrations at
      follow-up, which was a significant positive predictor of improved thyroid
      function. CONCLUSION: The results of the current study suggest that optimal
      thyroid function might require serum 25(OH)D concentrations above 125 nmol/L.
      Vitamin D supplementation may offer a safe and economical approach to improve
      thyroid function and may provide protection from developing thyroid disease.

PMID- 29067608
TI  - Microsurgical therapy of pituitary adenomas.
AB  - PURPOSE: We report the efficacy and safety of transsphenoidal microsurgery in a
      large and homogeneous cohort of patients with pituitary adenomas (PAs) treated at
      a single Institute by a single neurosurgeon. METHODS: A total of 2145 consecutive
      patients undergoing first surgery for a PA were included: 795 (37.1%) had a
      nonfunctioning pituitary adenoma (NFPA), 595 (27.7%) acromegaly, 496 (23.1%)
      Cushing's disease, 208 (9.7%) a PRL-secreting adenoma, and 51 patients (2.4%) a
      TSH-secreting adenoma. Remission was achieved when strict hormonal and
      radiological criteria were met. RESULTS: Early surgical remission was achieved in
      66% of acromegalic patients, 79.6% of patients with Cushing's disease, 64.4% of
      prolactinomas, 74.5% of patients with a TSH-secreting adenoma, and 66.9% of
      NFPAs. The mean (+/-SE) follow-up was 60.1 +/- 1.3 months. The recurrence-free
      survival at 10 years was 78.2% in acromegalic patients, 68.1% in prolactinomas,
      74.3% in Cushing's disease, 70.3% in TSH-secreting adenomas, and 75.3% in NFPAs.
      Preoperative hypoadrenalism recovered in 35.3%, hypogonadism in 43.3% and
      hypothyroidism in 37.4% of patients with impaired function before surgery. The
      mortality rate was 0.2% and major morbidity 2.1%. New onset hypoadrenalism
      occurred after surgery in 2.5% of patients at risk, hypogonadism in 4.1%, and
      hypothyroidism in 1.8%. Permanent diabetes insipidus (DI) occurred in 0.9% of
      patients. CONCLUSIONS: In experienced hands, transsphenoidal microsurgery for PAs
      achieves remission in most patients with a low complication rate. Pituitary
      function is preserved in most cases and can recover in more than one-third of
      patients with preoperative hypopituitarism.

PMID- 29067611
TI  - Residue analysis and risk assessment of pyrethrins in open field and greenhouse
      turnips.
AB  - A sensitive and selective method was developed and validated for the
      determination of pyrethrin residues in turnips (turnip leaves, turnip tubers, and
      the whole of plant) and cultivated soil using gas chromatography coupled with
      mass spectrometry (GC-MS). Six major components of pyrethrins (pyrethrin I and
      II, cinerin I and II, and jasmolin I and II) were separated and identified. The
      method involving solid-phase extraction (SPE) cleanup led to satisfactory average
      recoveries (88.1-104%) with limits of quantification (LOQs) of 0.05 mg/kg. The
      dissipation and final residue of pyrethrins in six provinces (among these places,
      two experiments were conducted in greenhouse and other four experiments in open
      filed) in China were studied. The trial results suggested that the half-lives of
      pyrethrins in the whole of turnips and soil were 0.5-1.6 and 1.0-1.3 days,
      respectively, and the degradation of pyrethrins in the greenhouse was quicker
      than that in open fields. The final residues of pyrethrins in turnip leaves and
      tubers were all below the maximum residue limit (MRL) established by the EU (1.0
      mg/kg). A pre-harvest interval of 2 days and MRL of 1.0 mg/kg are recommended to
      ensure food safety standards for pyrethrins in turnips. Long-term risk assessment
      and short-term risk assessment of turnip tubers were evaluated. Hazard quotient
      (HQ) and acute hazard index (aHI) were significantly less than 100%, indicating
      negligible risk for consumption of turnip tubers.

PMID- 29067610
TI  - Regulatory role of miR-18a to CCN2 by TGF-beta1 signaling pathway in pulmonary
      injury induced by nano-SiO2.
AB  - This research is designed to investigate the regulatory effect of miR-18a to the
      target gene connective tissue growth factor (CTGF, or CCN2), by participating in
      TGF-beta1 signaling pathway and explore the pathogenic mechanism of miR-18a in
      pulmonary injury induced by nano-SiO2 based on our early study. miR-18a and
      expression of TGF-beta1 in Chinese hamster lung (CHL) fibroblasts cells
      stimulated by supernatants of NR8383 cells exposed to 40 MUg/ml nano-SiO2 for 24
      h demonstrated 1.58 +/- 0.22-fold and 1096.00 +/- 2.60 pg/ml increase compared
      with blank control group analyzed by real-time quantitative PCR (RT-qPCR) and
      enzyme-linked immunosorbent assay (ELISA), respectively. Expression increase of
      miR-18a and reduction of CCN2 mRNA expression levels and protein gray value ratio
      detected by Western blotting in CHL cells transfect miR-18a mimics for 48 h. The
      reverse of CHL cell transfection miR-18a inhibit is also true. The result of miR
      18a and CCN2 binding sites tested by luciferase reporter gene assay shows that
      the report relative fluorescence value of miR-18a mimics wild type on CCN2 is
      0.50 +/- 0.02 with the control of mimics NC and mutant relative fluorescence
      report value 0.86 +/- 0.04 (P < 0.05). Expression levels of miR-18a, CCN2 mRNA,
      and protein gray value ratio decreased in CHL cells treated by TGF-beta1,
      respectively, and vice versa treated by TGF-beta1corepressor. The results suggest
      that CCN2 is the target gene regulated by miR-18a and miR-18a participates in TGF
      beta1 signaling pathway by regulating the expression of CCN2 negatively through
      CCN2 3'UTR site, and thus may be involved in the development process of pulmonary
      injury.

PMID- 29067609
TI  - Distribution and risk assessment of trace metals in sediments from Yangtze River
      estuary and Hangzhou Bay, China.
AB  - The Yangtze River estuary (YRE) and Hangzhou Bay (HZB) is of environmental
      significance because of the negative impact from industrial activities and rapid
      development of aquaculture on the south bank of HZB (SHZB) in recent years. This
      study investigated the distribution and risk assessments of trace metals (Cr, Cu,
      Zn, Hg, Pb, and Cd) accumulated in surface sediments by sampling in YRE, outer
      and south HZB. Copper and Zn concentration (avg. 35.4 and 98.7 mg kg-1,
      respectively) in surface sediments were generally higher than the background
      suggesting a widespread of Cu and Zn in the coastal area of Yangtze River Delta.
      High concentrations of Cu (~ 42 mg kg-1), Zn (~ 111 mg kg-1), Cd (~ 0.27 mg kg
      1), and Hg (~ 0.047 mg kg-1) were found in inner estuary of YRE and decreased
      offshore as a result of terrestrial input and dilution effect of total metal
      contents by "cleaner" sediments from the adjacent sea. In outer HZB, accumulation
      of terrestrial derived metal has taken place near the Zhoushan Islands. Increase
      in sediment metal concentration from the west (inner) to the east (outer) of SHZB
      gave rise to the input of fine-grained sediments contaminated with metals from
      outer bay. According the results from geoaccumulation index, nearly 75% of
      samples from YRE were moderately polluted (1.0 < I geo < 2.0) by Cd. Cadmium and
      Hg contributed for 80~90% to the potential ecological risk index in the YRE and
      HZB, with ~ 72% sites in HZB under moderate risk (150 <= RI < 300) especially
      near Zhoushan Islands.

PMID- 29067612
TI  - Sources of sulphate minerals in limestone cave-a possible evidence of
      anthropogenic activity: a case study in Crna Jama Cave (Slovenia).
AB  - In the caves, the formation of cave minerals is a consequence of a variety of
      chemical reactions, some of them also due to human activity. There are many caves
      in Slovenia, but sulphate minerals are not very often reported and analysed. In
      this study, the presence of sulphate minerals is detected by SEM/EDS analysis of
      speleothems from Crna Jama, a cave near Kocevje (southern Slovenia). The cave is
      characterised by its dark, almost black colour on cave walls, floor and
      speleothems. Anthropogenic influence in the cave is still visible, including the
      remains of a fireplace, some inscriptions on the walls and wooden containers. The
      analyses of some of the black-coated speleothems reveal the presence of calcium
      sulphate, confirmed by XRD as gypsum. Gypsum crystals are around 50 MUm in size,
      and they occur in thin crusts. Additionally, some rare authigenic baryte crystals
      a few micrometres in size are detected. The sulphates delta34S value in gypsum
      found on dark coloured speleothems is + 10.40/00 Vienna Canyon Diablo Troilite
      (VCDT), while the sulphate delta34S of the bedrock is + 8.60/00 VCDT. The more
      likely source of sulphate ions is thus biomass burning rather than bedrock. Also,
      bedrock and biomass ash are a very probable source of calcium and barium. The
      highly probable pyrogenous origin of sulphates draws attention to human impact on
      cave mineralogy.

PMID- 29067613
TI  - Treatment of PAH-contaminated soil using cement-activated persulfate.
AB  - In this study, a novel method for the treatment of polycyclic aromatic
      hydrocarbon -contaminated soil using cement-activated persulfate was developed.
      The removal of PAHs in soil rose with increasing initial persulfate
      concentration, initial Portland cement (PC) concentration, and oxidation reaction
      time. At an initial persulfate and PC concentration of 19.20 mmol/kg and 10% of
      soil weight and a reaction time of 2 h, the removal rate of PAHs reached 57.3%.
      Residual PAHs were mainly adsorbed within the soil granules and thus became less
      available. The mechanism of PC facilitating the oxidation reaction was that PC
      addition can increase the pH and temperature of the system. When the soil was
      stabilized/solidified by 10% of PC, the leaching concentration of PAHs and TOC
      was significantly higher than that leached from untreated soil. Persulfate
      oxidation decreased the leaching concentration of PAHs but increased the leaching
      concentration of TOC in solidification/stabilization products. The addition of
      activated carbon can decrease the leaching concentrations of both PAHs and TOC.
      Freeze-thaw durability tests revealed that the leachability of PAHs was not
      affected by freeze-thaw cycles. The unconfined compressive strength (UCS) of
      treated soil samples after 12 freeze-thaw cycles was only 49.0% of that curing
      for 52 days, but the UCS was still > 1 MPa. The treated soil samples can resist
      disintegration during the process of freeze-thaw cycles.

PMID- 29067614
TI  - QSAR modeling in ecotoxicological risk assessment: application to the prediction
      of acute contact toxicity of pesticides on bees (Apis mellifera L.).
AB  - Despite their indisputable importance around the world, the pesticides can be
      dangerous for a range of species of ecological importance such as honeybees (Apis
      mellifera L.). Thus, a particular attention should be paid to their protection,
      not only for their ecological importance by contributing to the maintenance of
      wild plant diversity, but also for their economic value as honey producers and
      crop-pollinating agents. For all these reasons, the environmental protection
      requires the resort of risk assessment of pesticides. The goal of this work was
      therefore to develop a validated QSAR model to predict contact acute toxicity
      (LD50) of 111 pesticides to bees because the QSAR models devoted to this species
      are very scarce. The analysis of the statistical parameters of this model and
      those published in the literature shows that our model is more efficient. The
      QSAR model was assessed according to the OECD principles for the validation of
      QSAR models. The calculated values for the internal and external validation
      statistic parameters (Q 2 and [Formula: see text] are greater than 0.85. In
      addition to this validation, a mathematical equation derived from the ANN model
      was used to predict the LD50 of 20 other pesticides. A good correlation between
      predicted and experimental values was found (R 2 = 0.97 and RMSE = 0.14). As a
      result, this equation could be a means of predicting the toxicity of new
      pesticides.

PMID- 29067615
TI  - An overview of municipal solid waste management and landfill leachate treatment:
      Malaysia and Asian perspectives.
AB  - Currently, generation of solid waste per capita in Malaysia is about 1.1 kg/day.
      Over 26,500 t of solid waste is disposed almost solely through 166 operating
      landfills in the country every day. Despite the availability of other disposal
      methods, landfill is the most widely accepted and prevalent method for municipal
      solid waste (MSW) disposal in developing countries, including Malaysia. This is
      mainly ascribed to its inherent forte in terms cost saving and simpler
      operational mechanism. However, there is a downside. Environmental pollution
      caused by the landfill leachate has been one of the typical dilemmas of
      landfilling method. Leachate is the liquid produced when water percolates through
      solid waste and contains dissolved or suspended materials from various disposed
      materials and biodecomposition processes. It is often a high-strength wastewater
      with extreme pH, chemical oxygen demand (COD), biochemical oxygen demand (BOD),
      inorganic salts and toxicity. Its composition differs over the time and space
      within a particular landfill, influenced by a broad spectrum of factors, namely
      waste composition, landfilling practice (solid waste contouring and compacting),
      local climatic conditions, landfill's physico-chemical conditions,
      biogeochemistry and landfill age. This paper summarises an overview of landfill
      operation and leachate treatment availability reported in literature: a broad
      spectrum of landfill management opportunity, leachate parameter discussions and
      the way forward of landfill leachate treatment applicability.

PMID- 29067616
TI  - A clinical review of phototherapy for psoriasis.
AB  - Psoriasis is an autoimmune inflammatory skin disease. In the past several
      decades, phototherapy has been widely used to treat stable psoriatic lesions,
      including trunk, scalp, arms and legs, and partial nail psoriasis. A variety of
      light/lasers with different mechanisms of action have been developed for
      psoriasis including ultraviolet B (UVB), psoralen ultraviolet A (PUVA), pulsed
      dye laser (PDL), photodynamic therapy (PDT), intense pulsed light (IPL), light
      emitting diodes (LED), and so on. Because light/laser each has specific
      therapeutic and adverse effects, it is important to adequately choose the sources
      and parameters in management of psoriasis with different pathogenic sites,
      severities, and duration of the disorder. This review aims at providing most
      updated clinic information to physicians about how to select light/laser sources
      and individual therapeutic regimens. To date, UV light is primarily for stable
      plaque psoriasis and PDL for topical psoriatic lesions with small area, both of
      which are safe and effective. On the other hand, PUVA has better curative effects
      than UVB for managing refractory psoriasis plaques, if its side effects can be
      better controlled. PDL provides optimal outcomes on nail psoriasis compared with
      other lasers. Although the trails of low-level light/laser therapy (LLLT) are
      still small, the near infrared (NIR) and visible red light with low energy show
      promise for treating psoriasis due to its strong penetration and encouraging
      photobiomodulation. IPL is rarely reported for psoriasis treatment, but PDT-IPL
      has been found to offer a moderate effect on nail psoriasis. In brief, various
      phototherapies have been used either in different combinations or as monotherapy.
      The modality has become a mainstay in the treatment of mild-to-moderate psoriasis
      without systemic adverse events in today's clinical practice.

PMID- 29067617
TI  - Study on mechanism of release oxygen by photo-excited hemoglobin in low-level
      laser therapy.
AB  - According to the calculated results on the charge distribution of oxygenated heme
      and deoxygenated heme, and based on the theory of electron excitations in photo
      acceptor molecules and the absorption spectra of hemoglobin, it is found that low
      level laser within the waveband of about 800-1060 nm can promote the release of
      oxygen from oxyhemoglobin and improve the oxygen supply of capillaries to
      surrounding tissues. Furthermore, the reasons have been explained that why the
      low-level laser at a wavelength of 830 nm is better in the treatment on burn
      injury and stimulation of hair growth. We also explained why the near-infrared
      laser of 1064 nm is applied to the forehead to improve cerebral oxygenation in
      healthy humans. Finally, according to comparison of atomic charge distribution in
      heme before and after bound to small molecule of carbon monoxide or nitric oxide,
      it could be inferred that the low-level laser with an appropriate wavelength can
      promote the carbon monoxide hemoglobin and nitric oxide hemoglobin to dissociate
      the carbon monoxide molecules and the nitric oxide molecules. This may be used
      for adjuvant therapy of carbon monoxide poisoning or nitric oxide poisoning.

PMID- 29067621
TI  - Erratum to: An Adaptable Polyethylene Glycol-Based Workflow for Proteomic
      Analysis of Extracellular Vesicles.

PMID- 29067619
TI  - Transparent model of temporal bone and vestibulocochlear organ made by 3D
      printing.
AB  - The vestibulocochlear organ is composed of tiny complex structures embedded in
      the petrous part of the temporal bone. Landmarks on the temporal bone surface
      provide the only orientation guide for dissection, but these need to be removed
      during the course of dissection, making it difficult to grasp the underlying
      three-dimensional structures, especially for beginners during gross anatomy
      classes. We report herein an attempt to produce a transparent three-dimensional
      printed model of the human ear. En bloc samples of the temporal bone from donated
      cadavers were subjected to computed tomography (CT) scanning, and on the basis of
      the data, the surface temporal bone was reconstructed with transparent resin and
      the vestibulocochlear organ with white resin to create a 1:1.5 scale model. The
      carotid canal was stuffed with red cotton, and the sigmoid sinus and internal
      jugular vein were filled with blue clay. In the inner ear, the internal acoustic
      meatus, cochlea, and semicircular canals were well reconstructed in detail with
      white resin. The three-dimensional relationships of the semicircular canals,
      spiral turns of the cochlea, and internal acoustic meatus were well recognizable
      from every direction through the transparent surface resin. The anterior
      semicircular canal was obvious immediately beneath the arcuate eminence, and the
      topographical relationships of the vestibulocochlear organ and adjacent great
      vessels were easily discernible. We consider that this transparent temporal bone
      model will be a very useful aid for better understanding of the gross anatomy of
      the vestibulocochlear organ.

PMID- 29067620
TI  - What Is "Enhanced Recovery," and How Can I Do It?
AB  - BACKGROUND: Enhanced recovery (ER) and fast-track protocols were initially
      implemented in the perioperative management of the surgical patient over 20 years
      ago. These standardized protocols are now broadly implemented across most
      surgical specialties for its many benefits. ER is well known for its positive
      effects on decreasing length of stay and complications. However, patient-centric
      outcomes for adequate pain control, functional recovery, costs, and overall
      patient experience are less considered. HOW I DO IT: A successful ER foundation
      stands on the pillars of several perioperative care principles: early feeding,
      early ambulation, goal-directed fluid therapy, and opiate-sparing analgesia.
      Moreover, it requires a multi-disciplinary team buy-in (including patient and
      family) that must also be thoughtfully executed. The following is a review of key
      elements within successful evidence-based ER protocols and relevant concepts to
      consider when starting a successful enhanced recovery program.

PMID- 29067618
TI  - Caffeine in the management of patients with headache.
AB  - Caffeinated headache medications, either alone or in combination with other
      treatments, are widely used by patients with headache. Clinicians should be
      familiar with their use as well as the chemistry, pharmacology, dietary and
      medical sources, clinical benefits, and potential safety issues of caffeine. In
      this review, we consider the role of caffeine in the over-the-counter treatment
      of headache. The MEDLINE and Cochrane databases were searched by combining
      "caffeine" with the terms "headache," "migraine," and "tension-type." Studies
      that were not placebo-controlled or that involved medications available only with
      a prescription, as well as those not assessing patients with migraine and/or
      tension-type headache (TTH), were excluded. Compared with analgesic medication
      alone, combinations of caffeine with analgesic medications, including
      acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved
      efficacy in the treatment of patients with TTH or migraine, with favorable
      tolerability in the vast majority of patients. The most common adverse events
      were nervousness (6.5%), nausea (4.3%), abdominal pain/discomfort (4.1%), and
      dizziness (3.2%). This review provides evidence for the role of caffeine as an
      analgesic adjuvant in the acute treatment of primary headache with over-the
      counter drugs, caffeine doses of 130 mg enhance the efficacy of analgesics in TTH
      and doses of >=100 mg enhance benefits in migraine. Additional studies are needed
      to assess the relationship between caffeine dosing and clinical benefits in
      patients with TTH and migraine.

PMID- 29067622
TI  - Factors Mediating Outcome After Stroke: Gender, Thrombolysis, and Their
      Interaction.
AB  - Several studies, but not all, have shown that women benefit more from intravenous
      thrombolysis than men; few have accounted for pre-stroke mobility. Our aim was to
      determine whether there was an interaction between gender and thrombolysis
      treatment in 3-month modified Rankin Scale (mRS) score, after adjusting for pre
      stroke mobility. We retrospectively reviewed medical records of 1390 consecutive
      ischemic stroke patients admitted between October 2012 and July 2015. The 3-month
      mRS was obtained from clinic visits. Thrombolysis-by-gender interaction was
      evaluated in univariate and multivariate analyses using ordinal logistic
      ("shift") regression with the full mRS range from 0 to 6 as the dependent
      variable. We included 926 (456 women and 470 men) patients with follow-up. Women
      were older (mean age 68.1 vs 65.8 years, P = 0.013), less likely to be treated
      with thrombolysis (15.6 vs 24.0%, P = 0.002), less often discharged to home (49.1
      vs 59.6%, P = 0.001), and more likely to use ambulation aids pre-stroke (13.6 vs
      8.5%, P = 0.014).Women had worse outcomes than men in those not treated with
      thrombolysis (mRS >= 3: 55.1 vs 40.1%, P < 0.001). In those who received
      thrombolysis, there were no gender differences (47.9 vs 50.4%, P = 0.736). In
      multivariable modeling, there was a significant gender-treatment interaction (P <
      0.001), after adjustment for gender, pre-stroke ambulation aid use, age, age-by
      gender interaction, initial stroke severity, diabetes, heart failure, and prior
      stroke. Our results show that women benefit from thrombolysis more than men, and
      the thrombolysis-by-gender interaction persists after adjustment for pre-stroke
      mobility impairment.

PMID- 29067623
TI  - Risk factors for pneumococcal endocarditis.
AB  - Bacteremia is one of the most common manifestations of invasive pneumococcal
      disease (IPD). One complication of bacteremia is endocarditis; yet, few studies
      have evaluated the overall incidence and risk factors for IPD-associated
      endocarditis. Thus, we evaluated the overall incidence and risk factors of
      endocarditis compared to those without endocarditis in a large population of IPD
      patients. We prospectively collected all IPD cases from 2000 to 2014 in Northern
      Alberta, Canada. Descriptive statistics were used to compare sociodemographic
      variables, clinical characteristics, and IPD-related outcomes between patients
      with and without endocarditis. Endocarditis complicated the course of only 28
      (0.3%) of 3251 adult patients with IPD. Endocarditis patients were more likely to
      use illicit drugs and have a higher severity of illness at presentation (i.e.,
      higher rate of altered mental status and rate of intensive care unit [ICU]
      utilization, p < 0.05); however, no other major risk factors were identified. New
      murmur development among endocarditis patients was common: 39.3% compared to 2.2%
      of non-endocarditis patients (p < 0.001). The mortality rate of 39.3% was more
      than twice that of the rate of 14.7% for the patients with IPD but without
      endocarditis. There was no pneumococcal serotype predilection for endocarditis.
      Endocarditis is an uncommon complication of IPD, but, when present, is associated
      with a significantly increased risk of mortality. Overall, few specific risk
      factors were identified for IPD-related endocarditis, with the exception of
      illicit drug use.

PMID- 29067625
TI  - Central Europe: Ethical Overlaps of Environmental and Economic Interests in
      Coming Years.
AB  - Despite the size and thanks to the rich brown coal reserves, the Czech Republic
      is one of the leading energy producers in Europe, and the 7th biggest exporter of
      electricity in the world. However, following the climate change mitigation, the
      novel energy policy that enhances the reduction of coal mining is about to be
      implemented. A preliminary material flow analysis of the Czech energy sector was
      carried out. The data obtained confirmed that this government act would result in
      a dramatic reduction of revenues from electricity sales. Conversely, increased
      costs would be necessary in order to modernize nuclear power plants and promote
      the production of renewable energy. In addition, the economic analysis revealed
      that the act might be prejudicial to economic relations in Central and Western
      European countries as some of them are significantly dependent on the electricity
      imported from the Czech Republic. Disputes between engineers and politicians were
      highlighted. The aforementioned interrelations were subsequently analyzed and a
      conclusion was made stating that global interests should have the highest moral
      priority.

PMID- 29067624
TI  - Are guidelines on the management of non-tuberculous mycobacteria lung infections
      respected and what are the consequences for patients? A French retrospective
      study from 2007 to 2014.
AB  - Diagnosis and treatment of lung infections caused by non-tuberculous mycobacteria
      (NTM) remain challenging. Adherence of the clinicians to the American Thoracic
      Society (ATS) and the Infectious Diseases Society of America (IDSA) 2007
      guidelines is often incomplete. Between 2007 and 2014, in Grenoble Alpes
      University Hospital, France, 132 patients had NTM-positive cultures from lower
      respiratory tract (LRT) samples. We retrospectively collected diagnosis,
      treatment, and outcome data of patients, and evaluated the adherence of
      clinicians to ATS/IDSA guidelines and the consequences of patients' prognoses.
      Using the ATS/IDSA definitions, 31 out of 132 patients (23.5%) were considered
      infected, 57 out of 132 patients (43.2%) were considered colonised, 33 out of 132
      (25%) were contaminated and 11 (8.4%) had missing data. Among the 31 NTM-infected
      patients, M. avium (23 out of 31, 74.2%) was most frequently involved. The main
      risk factor for NTM lung infection was underlying lung disease (30 out of 31,
      96.8%). Treatment was not appropriate according to current guidelines in 58.1% of
      infected patients (18 out of 31). Mainly, the antibiotic treatment was installed
      based on radiological signs (p = 0.0006), sputum results and bronchoalveolar
      lavage results (p < 0.0001 and p = 0.003 respectively). Most antibiotic regimens
      included a macrolide (83.4%). Patients receiving appropriate treatment had the
      same cure rates as those receiving inappropriate treatment (p = 0.22) and similar
      relapse rates (p = 0.92). Current medical practices for the treatment of NTM lung
      infections in our institution are not consistent with the ATS/IDSA guidelines.
      This could potentially affect the prognosis of these patients and favour the
      emergence of macrolide resistance in NTM species.

PMID- 29067628
TI  - Two-Year Follow-Up of Fall Prediction Among Older Adults in an Independent-Living
      Community.
AB  - Adults over the age of 70 are at risk of falls. Early detection of risk of falls
      can suggest early interventions. In this study, we attempted to determine valid
      clinical tests that can differentiate older individuals who are at risk of
      falling. Older adults from an independent-living community volunteered to
      participate in this descriptive, cohort study. They were administered the Berg
      Balance Scale (BBS), Zur Balance Scale (ZBS), Head Shaking Nystagmus Head Impulse
      Test, Dynamic Visual Acuity, and the Hallpike maneuver for evaluating benign
      paroxysmal positional vertigo (BPPV); a questionnaire including sociodemographics
      and a health characteristics survey. Multivariate analysis indicated that a ZBS
      score < 51, previous fall, and number of medications strongly predict falls in
      older adults. ZBS score, BBS score, Hallpike maneuver, number of medications,
      deficit of vestibular ocular reflex, along with positive ZBS score and past fall
      differentiate between fallers and non-fallers. ZBS <51, taking >6 medications,
      and history of falls were a benchmark for high-risk of falling.

PMID- 29067627
TI  - Physical Functioning and Symptoms of Chronic Fatigue in Sarcoidosis Patients.
AB  - Scientific reports underscore the importance of measuring the health-related
      quality of life in sarcoidosis patients. The present study seeks to define how
      sarcoidosis patients' quality of life, daily physical activity, and physical
      performance are related to each other. Seventeen patients (mean age 46.8 +/- 8.8
      years) suffering from sarcoidosis completed the following questionnaires: the
      fatigue assessment scale (FAS), the quality of life scale (SF-36 questionnaire),
      and the Borg dyspnea scale. Physical activity (PA) was assessed using
      accelerometry. Respiratory function, consisting of forced expiratory volume in
      one second (FEV1), forced vital capacity (FVC), forced expiratory volume in one
      second as a percentage of vital capacity (FEV1/%FVC), and diffusing capacity of
      the lungs for carbon monoxide (DLCO), were assessed. In addition, performance in
      6-min walk test (MWT), aerobic capacity assessed from maximal oxygen uptake
      (VO2max), and the metabolic equivalent of task (MET) were evaluated. We found
      that daily PA (4566 +/- 2378 steps/day) and VO2max (21.8 +/- 5.9 ml/kg/min) were
      lower in sarcoidosis patients than the known predicted values in healthy age
      matched individuals. There were significant inverse associations between the FAS
      score and 6MWT (r = -0.62; p < 0.01), and between SF-36 score and 6MWT (r = 
      0.55; p < 0.03). In contrast, SF-36 scores associated with fatigue and dyspnea
      scores (r = 0.72; p < 0.001 and r = 0.85; p < 0.001). These findings imply that
      sarcoidosis patients are less active compared with healthy subjects. The FAS and
      SF-36 scales seem to be effective tools for assessing the severity of fatigue in
      sarcoidosis patients.

PMID- 29067626
TI  - The influence of antibiotic-loaded cement spacers on the risk of reinfection
      after septic two-stage hip revision surgery.
AB  - PURPOSE: The aim of this study was the evaluation of possible outcome differences
      of patients undergoing two-stage hip exchange with antibiotic-loaded spacers,
      compared to patients without an interim spacer implantation. METHODS: We
      evaluated 46 patients undergoing two-stage hip revision surgery. Twenty-five
      patients received an interim ALS. Additional to a Kaplan-Meier survival analysis,
      a competing risk analysis was performed to estimate the cumulative incidence
      function for re-revisions due to infection accounting for death as a competing
      event. RESULTS: Nine patients (seven non-ALS vs. two ALS) had to undergo re
      revision surgery due to reinfection of the hip joint. The non-ALS group showed a
      risk of re-revision of 19% (95% CI 5-38%) at 12 and 24 months and 30% (95% CI 12
      51%) at 36 months. The group with ALS implantation displayed a 0% risk of re
      revision surgery in the first 36 months. The Gray test revealed a significant
      difference in the cumulative incidence between both observed groups (p = 0.026).
      CONCLUSION: Our findings suggest that ALS implantation significantly reduces the
      risk of reinfection after two-stage hip revision surgery.

PMID- 29067629
TI  - Multifactorial examination of sex-differences in head injuries and concussions
      among collegiate soccer players: NCAA ISS, 2004-2009.
AB  - BACKGROUND: While head injuries and concussions are major concerns among soccer
      players, the multifactorial nature of head injury observations in this group
      remains relatively undefined. We aim to extend previous analyses and examine sex
      differences in the incidence of head injuries, odds of head injuries within an
      injured sample, and severity of head injuries, among collegiate soccer players
      between 2004 and 2009. METHODS: Data collected within the National Collegiate
      Athletic Association (NCAA) Injury Surveillance System (ISS) between the years of
      2004 and 2009, were analyzed in this study. Unadjusted rate ratios (RR), compared
      incidence rates between categories of sex, injury mechanism, setting and
      competition level. We also examined sex-differences in head injury incidence
      rates, across categories of the other covariates. Multivariable logistic
      regression and negative binomial regression modeling tested the relation between
      sex and head injury corollaries, while controlling for contact, setting, and
      competition level. RESULTS: Between 2004 and 2009, head injuries accounted for
      approximately 11% of all soccer-related injuries reported within the NCAA-ISS.
      The rate of head injuries among women was higher than among men (RR = 1.23, 95%
      CI = [1.08, 1.41]). The rate of head injuries due to player-to-player contact was
      comparable between women and men (RR = 0.95, 95% CI = [0.81, 1.11]). Whereas, the
      rate of injury due to contact with apparatus (ball/goal) was nearly 2.5 times
      higher (RR = 2.46, 95% CI = [1.76, 3.44]) and the rate due to contact with a
      playing surface was over two times higher (RR = 2.29, 95% CI = [1.34, 3.91]) in
      women than in men. In our multifactorial models, we also observed that the
      association between sex and head injury corollaries varied by injury mechanism.
      CONCLUSIONS: Sex-differences in the incidence, odds (given an injury), and
      severity (concussion diagnosis, time-loss) of head injuries varied by injury
      mechanism (player-to-player contact vs. all other mechanisms) in this sample.

PMID- 29067632
TI  - A National Trial on Differences in Cerebral Perfusion Pressure Values by
      Measurement Location.
AB  - BACKGROUND: Cerebral perfusion pressure (CPP) is a key parameter in management of
      brain injury with suspected impaired cerebral autoregulation. CPP is calculated
      by subtracting intracranial pressure (ICP) from mean arterial pressure (MAP).
      Despite consensus on importance of CPP monitoring, substantial variations exist
      on anatomical reference points used to measure arterial MAP when calculating CPP.
      This study aimed to identify differences in CPP values based on measurement
      location when using phlebostatic axis (PA) or tragus (Tg) as anatomical reference
      points. The secondary study aim was to determine impact of differences on patient
      outcomes at discharge. METHODS: This was a prospective, repeated measures, multi
      site national trial. Adult ICU patients with neurological injury necessitating
      ICP and CPP monitoring were consecutively enrolled from seven sites. Daily
      MAP/ICP/CPP values were gathered with the arterial transducer at the PA, followed
      by the Tg as anatomical reference points. RESULTS: A total of 136 subjects were
      enrolled, resulting in 324 paired observations. There were significant
      differences for CPP when comparing values obtained at PA and Tg reference points
      (p < 0.000). Differences remained significant in repeated measures model when
      controlling for clinical factors (mean CPP-PA = 80.77, mean CPP-Tg = 70.61, p <
      0.000). When categorizing CPP as binary endpoint, 18.8% of values were identified
      as adequate with PA values, yet inadequate with CPP values measured at the Tg.
      CONCLUSION: Findings identify numerical differences for CPP based on anatomical
      reference location and highlight importance of a standard reference point for
      both clinical practice and future trials to limit practice variations and
      heterogeneity of findings.

PMID- 29067630
TI  - Pulmonary Aspergillus Overlap Syndromes.
AB  - BACKGROUND: Broadly, there are three main categories in pulmonary aspergillosis:
      chronic forms of aspergillosis; allergic bronchopulmonary aspergillosis; and
      invasive aspergillosis (IPA). IPA has been further subdivided into angioinvasive
      and airway-invasive aspergillosis. Aspergillus overlap syndromes is defined as
      the occurrence of more than one form aspergillus disease in a single individual.
      OBJECTIVES: To help clinicians correctly deal with AOS. METHODS: Retrospectively
      study the clinical findings of nine patients presenting with AOS. RESULTS: Four
      cases were diagnosed as angioinvasive aspergillosis complicated with ABPA, three
      cases as IPA overlap aspergilloma, and two cases as ABPA with AWIA. All the
      patients presented with cough and expectoration. In three patients with IPA
      overlap aspergilloma, two had hemoptysis, two had wheezing and fever. All of
      patients with IPA overlap ABPA had wheezing, dyspnea, and fever, three had sputum
      plugs, two had hemoptysis, and five patients had mucopurulent discharge and
      rhonchi in auscultation. Their total IgE ranged from 129 to 2124 IU/ml (676.5 +/-
      557.33 IU/ml). Fungal culture in sputum showed A. Fumigatus in three patients.
      All the six patients with IPA overlap ABPA applied steroid therapy and antifungal
      therapy. Three of them received two or more antifungal drugs successively, and
      three received combinational therapy. All the patients improved except one
      diagnosed ABPA overlap IPA. CONCLUSIONS: Clinical manifestation of AOS is not
      typical. Poor first-line therapeutic effects and complicated diagnosis criteria
      require clinicians to be aware of AOS when facing patients with aspergillosis.

PMID- 29067631
TI  - Dermatomycoses Due to Nannizzia praecox (Formerly Microsporum praecox) in
      Germany: Case Reports and Review of the Literature.
AB  - Nannizzia praecox, formerly known as Microsporum praecox, is a geophilic
      dermatophyte. Up to now 31 cases of human tinea have been reported in the
      literature, most of them with an inflammatory course. Three recent cases
      diagnosed in Germany within 1 year suggest that the fungus might be a more common
      cause of human dermatophytosis than reported so far. This might be based on the
      fact that N. praecox is often found in an equine environment and that horse
      riding is becoming more popular recently.

PMID- 29067633
TI  - Implementation of Continuous Video-Electroencephalography at a Community Hospital
      Enhances Care and Reduces Costs.
AB  - BACKGROUND: Despite data indicating the importance of continuous video
      electroencephalography (cvEEG) monitoring, adoption has been slow outside major
      academic centers. Barriers to adoption include the need for technologists,
      equipment, and cvEEG readers. Advancements in lower-cost lead placement templates
      and commercial systems with remote review may reduce barriers to allow community
      centers to implement cvEEG. Here, we report our experience, lessons learned, and
      financial impact of implementing a community hospital cvEEG-monitoring program.
      METHODS: We implemented an adult cvEEG service at Duke Regional Hospital (DRH), a
      community hospital affiliate, in June of 2012. Lead placement templates were used
      in the implementation to reduce the impact on technologists by using other
      bedside providers for EEG initiation. Utilization of the service, study quality,
      and patient outcomes were tracked over a 3-year period following initiation of
      service. RESULTS: Service was implemented at essentially no cost. Utilization
      varied from a number of factors: intensive care unit (ICU) attending awareness,
      limited willingness of bedside providers to perform lead placement, and variation
      in practice of the consulting neurologists. A total of 92 studies were performed
      on 88 patients in the first 3 years of the program, 24 in year one, 27 in year
      two, and 38 in year three, showing progressive adoption. Seizures were seen in 25
      patients (27%), 19 were in status, of which 18 were successfully treated.
      Transfers to the main hospital, Duke University Medical Center, were prevented
      for 53 patients, producing an estimated cost savings of $145,750. The retained
      patients produced a direct contribution margin of about $75,000, and the margin
      was just over $100,000 for the entire monitored cohort. CONCLUSION: ICU cvEEG
      service is feasible and practical to implement at the community hospital level.
      Service was initiated at little to no cost and clearly enhanced care, increased
      breadth of care, increased ICU census, and reduced transfers. The system allowed
      for successful management of ICU patients with underlying seizures and eliminated
      interfacility transfers, producing a savings of $145,750. The savings combined
      with the retained patient revenue produced a total revenue of over $250,000 with
      additional revenue in professional services as well. These results suggest
      expansion of cvEEG monitoring to community ICUs is practical, financially
      sustainable, improves the level and quality of care, and reduces costs.

PMID- 29067634
TI  - Best practice in major elective rectal/pelvic surgery: enhanced recovery after
      surgery (ERAS).
AB  - Within traditional clinical care, the postoperative recovery after pelvic/rectal
      surgery has been slow with high morbidity and long hospital stay. The enhanced
      recovery after surgery program is a multimodal approach to perioperative care
      designed to accelerate recovery and safely reduce hospital stay. This review will
      briefly summarize optimal perioperative care, before, during and after surgery in
      this group of patients and issues related to implementation and audit.

PMID- 29067636
TI  - A novel finding of Rapunzel syndrome.
AB  - Rapunzel syndrome is a rare form of gastric trichobezoar (hair ball) involving
      extension of a tail of the hair into the small bowel. A 13-year-old girl was
      admitted with a 4-day history of epigastric pain and nausea which worsened after
      meals. Abdominal ultrasound showed duodenal wall thickening and lymphadenopathy.
      Esophagogastroduodenoscopy identified a gastric trichobezoar with a tail
      extending into the duodenum. In addition, multiple longitudinal duodenal and
      jejunal ulcers were noted. The ulcers appeared to be a result of direct pressure
      by the tail itself against the intestinal mucosa. The trichobezoar was
      successfully retrieved endoscopically under general anesthesia. Her symptoms
      resolved completely after retrieval. Psychiatric follow-up was carried out to
      help reduce the risk of recurrence. Here, we describe a novel complication of
      Rapunzel syndrome, i.e., multiple longitudinal ulcers of the small intestine.
      This novel finding suggests that the mucosal damage caused by the trichobezoar of
      Rapunzel syndrome can occur in an earlier stage than previously thought. In
      addition, we also strongly recommend using general anesthesia with intubation
      when removing a gastric trichobezoar to ensure protection of the airway.

PMID- 29067635
TI  - Interferon regulated gene (IRG) expression-signature in a mouse model of
      chikungunya virus neurovirulence.
AB  - Interferon regulated genes (IRGs) are critical in controlling virus infections.
      Here, we analyzed the expression profile of IRGs in the brain tissue in a mouse
      model of chikungunya virus (CHIKV) neurovirulence. Neurovirulence is one of the
      newer complications identified in disease caused by re-emerging strains of CHIKV,
      an alphavirus with positive-strand RNA in the Togaviridae family. In microarray
      analysis, we identified significant upregulation of 269 genes, out of which a
      predominant percentage (76%) was IRGs. The highly modulated IRGs included Ifit1,
      Ifi44, Ddx60, Usp18, Stat1, Rtp4, Mnda, Gbp3, Gbp4, Gbp7, Oasl2, Oas1g, Ly6a,
      Igtp, and Gbp10, along with many others exhibiting lesser changes in expression
      levels. We found that these IRG mRNA transcripts are modulated in parallel across
      CHIKV-infected mouse brain tissues, human neuronal cell line IMR-32 and hepatic
      cell line Huh-7. The genes identified to be highly modulated both in mouse brain
      and human neuronal cells were Ifit1, Ifi44, Ddx60, Usp18, and Mnda. In Huh-7
      cells, however, only two IRGs (Gbp4 and Gbp7) showed a similar level of
      upregulation. Concordant modulation of IRGs in both mice and human cells
      indicates that they might play important roles in regulating CHIKV replication in
      the central nervous system (CNS). The induction of several IRGs in CNS during
      infection underscores the robustness of IRG-mediated innate immune response in
      CHIKV restriction. Further studies on these IRGs would help in evolving
      possibilities for their targeting in host-directed therapeutic interventions
      against CHIKV.

PMID- 29067637
TI  - Use of the familiarity difference cue in inferential judgments.
AB  - The familiarity difference cue has been regarded as a general cue for making
      inferential judgments (Honda, Abe, Matsuks, & Yamagishi in Memory and Cognition,
      39(5), 851-863, 2011; Schwikert & Curran in Journal of Experimental Psychology:
      General, 143(6), 2341-2365, 2014). The current study tests a model of inference
      based on familiarity differences that encompasses the recognition heuristic
      (Goldstein & Gigerenzer, 1999, Goldstein & Gigerenzer in Psychological Review,
      109(1), 75-90, 2002). In two studies, using a large pool of stimuli, participants
      rated their familiarity of cities and made choices on a typical city-size task.
      The data were fitted with the r-s model (Hilbig, Erdfelder, & Pohl in, Journal of
      Experimental Psychology: Learning Memory and Cognition, 37(4), 827-839, 2011),
      which was adapted to include familiarity differences. The results indicated that
      people used the familiarity difference cue because the participants ignored
      further knowledge in a substantial number of cases when the familiarity
      difference cue was available. An analysis of reaction-time data further indicated
      that the response times were shorter for heuristic judgments than for knowledge
      only-based judgments. Furthermore, when knowledge was available, the response
      times were shorter when knowledge was congruent with a heuristic cue than when it
      was in conflict with it. Differences between the familiarity difference cue and
      the fluency heuristic (Schooler & Hertwig, 2005, Psychological Review, 112, 610
      628) are discussed.

PMID- 29067638
TI  - Climate change, future Arctic Sea ice, and the competitiveness of European Arctic
      offshore oil and gas production on world markets.
AB  - A significant share of the world's undiscovered oil and natural gas resources are
      assumed to lie under the seabed of the Arctic Ocean. Up until now, the
      exploitation of the resources especially under the European Arctic has largely
      been prevented by the challenges posed by sea ice coverage, harsh weather
      conditions, darkness, remoteness of the fields, and lack of infrastructure.
      Gradual warming has, however, improved the accessibility of the Arctic Ocean. We
      show for the most resource-abundant European Arctic Seas whether and how a
      climate induced reduction in sea ice might impact future accessibility of
      offshore natural gas and crude oil resources. Based on this analysis we show for
      a number of illustrative but representative locations which technology options
      exist based on a cost-minimization assessment. We find that under current
      hydrocarbon prices, oil and gas from the European offshore Arctic is not
      competitive on world markets.

PMID- 29067639
TI  - Impact of climate change and seasonal trends on the fate of Arctic oil spills.
AB  - We investigated the effects of a warmer climate, and seasonal trends, on the fate
      of oil spilled in the Arctic. Three well blowout scenarios, two shipping
      accidents and a pipeline rupture were considered. We used ensembles of numerical
      simulations, using the OSCAR oil spill model, with environmental data for the
      periods 2009-2012 and 2050-2053 (representing a warmer future) as inputs to the
      model. Future atmospheric forcing was based on the IPCC's A1B scenario, with the
      ocean data generated by the hydrodynamic model SINMOD. We found differences in
      "typical" outcome of a spill in a warmer future compared to the present, mainly
      due to a longer season of open water. We have demonstrated that ice cover is
      extremely important for predicting the fate of an Arctic oil spill, and find that
      oil spills in a warming climate will in some cases result in greater areal
      coverage and shoreline exposure.

PMID- 29067640
TI  - Environmental impact of exhaust emissions by Arctic shipping.
AB  - Since 2005, a dramatic decline of the Arctic sea-ice extent is observed which
      results in an increase of shipping activities. Even though this provides
      commercial and social development opportunities, the resulting environmental
      impacts need to be investigated and monitored. In order to understand the impact
      of shipping in arctic areas, the method described in this paper determines the
      travel time, fuel consumption and resulting exhaust emissions of ships navigating
      in arctic waters. The investigated case studies are considering ship particulars
      as well as environmental conditions with special focus on ice scenarios. Travel
      time, fuel consumption and exhaust gas emission were investigated for three
      different vessels, using different passages of the Northern Sea Route (NSR) in
      different seasons of years 1960, 2000 and 2040. The presented results show the
      sensitivity of vessel performance and amount of exhaust emissions to optimize
      arctic traffic with respect to efficiency, safety and environmental impact.

PMID- 29067641
TI  - ACCESS climate data management.
AB  - Building on achievements and experience gained through the EU project DAMOCLES
      and international data management during the International Polar Year, ACCESS,
      data management was implemented using the same platform as used for DAMOCLES. A
      metadata-driven approach through which all datasets are properly described with
      discovery and use metadata was chosen in order to simplify data management and
      data usage. The system provides automated submission and checking of datasets,
      search and download as well as visualisation and transformation on user demand
      and metadata export. Long-term management of ACCESS climate datasets is done
      within the context of the Arctic Data Centre. This ensures visibility of ACCESS
      datasets in the context of WMO and GEOSS catalogues. Challenges with ACCESS data
      management have mainly been cultural with the consequence that the system has
      been underutilised within the duration of the project duration.

PMID- 29067642
TI  - Arctic Climate Change, Economy and Society (ACCESS): Integrated perspectives.
AB  - This introduction to the special issue presents an overview of the wide range of
      results produced during the European Union project Arctic Climate Change, Economy
      and Society (ACCESS). This project assessed the main impacts of climate change on
      Arctic Ocean's geophysical variables and how these impending changes could be
      expected to impact directly and indirectly on socio-economic activities like
      transportation, marine sea food production and resource exploitation. Related
      governance issues were examined. These results were used to develop several
      management tools that can live on beyond ACCESS. In this article, we synthesize
      most of the project results in the form of tentative responses to questions
      raised during the project. By doing so, we put the findings of the project in a
      broader perspective and introduce the contributions made in the different
      articles published in this special issue.

PMID- 29067645
TI  - Secretome profiling reveals temperature-dependent growth of Aspergillus
      fumigatus.
AB  - Aspergillus fumigatus is a ubiquitous opportunistic fungus. In this study,
      systematic analyses were carried out to study the temperature adaptability of A.
      fumigatus. A total of 241 glycoside hydrolases and 69 proteases in the secretome
      revealed the strong capability of A. fumigatus to degrade plant biomass and
      protein substrates. In total, 129 pathogenesis-related proteins detected in the
      secretome were strongly correlated with glycoside hydrolases and proteases. The
      variety and abundance of proteins remained at temperatures of 34 degrees C-45
      degrees C. The percentage of endo-1,4-xylanase increased when the temperature was
      lowered to 20 degrees C, while the percentage of cellobiohydrolase increased as
      temperature was increased, suggesting that the strain obtains carbon mainly by
      degrading xylan and cellulose, and the main types of proteases in the secretome
      were aminopeptidases and carboxypeptidases. Only half of the proteins were
      retained and their abundance declined to 9.7% at 55 degrees C. The activities of
      the remaining beta-glycosidases and proteases were merely 35% and 24%,
      respectively, when the secretome was treated at 60 degrees C for 2 h. Therefore,
      temperatures >60 degrees C restrict the growth of A. fumigatus.

PMID- 29067644
TI  - Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with the
      Second-Generation ALK Inhibitor Ceritinib.
AB  - BACKGROUND: The receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK)
      has been implicated in the tumorigenesis of rhabdomyosarcoma (RMS). However, the
      exact role of ALK in RMS is debatable and remains to be elucidated. OBJECTIVE: To
      determine the in vitro and in vivo effects and mechanism of action of the second
      generation ALK inhibitor ceritinib on RMS cell growth. METHODS: Effects of
      ceritinib on cell proliferation, wound healing, cell cycle, and RTK signaling
      were determined in alveolar and embryonal rhabdomyosarcoma (ARMS, ERMS). In
      addition, possible synergistic effects of combined treatment with ceritinib and
      the Abl/Src family kinase inhibitor dasatinib were determined. RESULTS: Ceritinib
      treatment led to decreased cell proliferation, cell cycle arrest, apoptosis, and
      decreased in vivo tumor growth for the ARMS subtype. ERMS cell lines were less
      affected and showed no cell cycle arrest or apoptosis. Both subtypes lacked
      intrinsic ALK phosphorylation, and ceritinib was shown to affect the IGF1R
      signaling pathway. High levels of phosphorylated Src (Tyr416) were present
      following ceritinib treatment, making combined treatment with a Src inhibitor a
      potential treatment option. Combined treatment of ceritinib and dasatinib showed
      synergistic effects in both ERMS and ARMS cell lines. CONCLUSION: This study
      shows that monotherapy with an ALK inhibitor, such as ceritinib, in RMS, has no
      effect on ALK signaling. However, the synergistic effects of ceritinib and
      dasatinib are promising, most probably due to targeting of IGF1R and Src.

PMID- 29067643
TI  - A Multi-Arm Phase I Study of the PI3K/mTOR Inhibitors PF-04691502 and Gedatolisib
      (PF-05212384) plus Irinotecan or the MEK Inhibitor PD-0325901 in Advanced Cancer.
AB  - BACKGROUND: This phase I, four-arm, open-label study (NCT01347866) evaluated the
      PI3K/mTOR inhibitors PF-04691502 (arms A, B) and gedatolisib (PF-05212384; arms
      C, D) in combination with the MEK inhibitor PD-0325901 (arm A, D) or irinotecan
      (arm B, C) in patients with advanced solid tumors. OBJECTIVES: Primary endpoint
      was dose-limiting toxicity with each combination. Secondary endpoints included
      safety, pharmacokinetics and preliminary antitumor activity. PATIENTS AND
      METHODS: Dose escalation followed a 3 + 3 design in arm C and a zone-based design
      in arm D. RESULTS: The PF-04691502 combination arms were closed prematurely due
      to low tolerability, and the maximum tolerated doses (MTDs) were not determined
      for either arm. The MTD for the combination of gedatolisib with irinotecan 180
      mg/m2 was estimated to be 110 mg weekly and for the combination with PD-0325901
      was not reached at the highest dose evaluated (gedatolisib 154 mg weekly). Plasma
      concentrations of gedatolisib were generally similar across dose groups in arm C
      (with irinotecan) and arm D (with PD-0325901). Frequent dose delays or dose
      reductions were required for both combinations, potentially preventing sustained
      therapeutic drug concentrations. Gedatolisib plus irinotecan produced a response
      rate of ~5% and clinical benefit in 16% of patients with advanced colorectal
      cancer (progression-free survival, 2.8 months). Preliminary evidence of clinical
      activity was observed with gedatolisib plus PD-0325901 in patients with ovarian
      cancer (three partial responses, n = 5) or endometrial cancer (one partial
      response, n = 1) and KRAS mutations. CONCLUSIONS: Further evaluations of
      gedatolisib are warranted in patients with advanced solid malignancies.

PMID- 29067646
TI  - The oxidative DNA damage response: A review of research undertaken with Tsinghua
      and Xiangya students at the University of Pittsburgh.
AB  - Endogenous stress and exogenous toxicants (chemicals and UV light) alter genetic
      information either directly or indirectly through the production of reactive
      oxygen species (ROS), thereby driving genomic instability in cells and promoting
      tumorigenesis. All living cells try to faithfully preserve and transmit their
      genomic information from one generation to the next using DNA repair mechanisms
      to repair oxidative DNA damage to prevent cancer or premature aging. Oxidative
      DNA damage comprises a mixture of DNA lesions including base damage, DNA single
      strand breaks (SSBs), and DNA double strand breaks (DSBs). This review summarizes
      some of the studies on DNA damage response at a defined genome locus that are
      performed by students from the Tsinghua University School of Medicine and the
      School of Medicine of Central South University (Xiangya Hospital) at the
      University of Pittsburgh School of Medicine. A summary of their work highlights
      the continuous contribution of the students to a particular research program and
      exemplifies the achievements of this China-U.S. collaborative training program.

PMID- 29067647
TI  - Sino-U.S. partnerships in research, education, and patient care: The experience
      of the University of Pittsburgh and UPMC.
AB  - In 2011, the University of Pittsburgh School of Medicine (UPSOM) and Tsinghua
      University formed a partnership to further the education of Tsinghua medical
      students. These students come to UPSOM as visiting research scholars for two
      years of their eight-year MD curriculum. During this time, the students, who have
      completed four years at Tsinghua, work full-time in medical school laboratories
      and research programs of their choice, essentially functioning as graduate
      students. In their first two months in Pittsburgh, the scholars have a one-week
      orientation to biomedical research, followed by two-week rotations in four labs
      selected on the basis of the scholars' scientific interests, after which they
      choose one of these labs for the remainder of the two years. Selected labs may be
      in basic science departments, basic science divisions of clinical departments, or
      specialized centers that focus on approaches like simulation and modeling. The
      Tsinghua students also have a brief exposure to clinical medicine. UPSOM has also
      formed a similar partnership with Central South University Xiangya School of
      Medicine in Changsha, Hunan Province. The Xiangya students come to UPSOM for two
      years of research training after their sixth year and, thus, unlike the Tsinghua
      students, have already completed their clinical rotations. UPSOM faculty members
      have also paved the way for UPMC (University of Pittsburgh Medical Center),
      UPSOM's clinical partner, to engage with clinical centers in China. Major
      relationships involving advisory, training, managerial, and/or equity roles exist
      with Xiangya International Medical Center, KingMED Diagnostics, First Chengmei
      Medical Industry Group, and Macare Women's Hospital. Both UPSOM and UPMC are
      actively exploring other clinical and academic opportunities in China.

PMID- 29067648
TI  - Biosynthesis and functions of metabolites.

PMID- 29067649
TI  - Interplay between TGF-beta signaling and receptor tyrosine kinases in tumor
      development.
AB  - Transforming growth factor-beta (TGF-beta) signaling regulates cell
      proliferation, differentiation, migration and death, and plays a critical role in
      embryogenesis and tissue homeostasis. Its deregulation results in various
      diseases including tumor formation. Receptor tyrosine kinases (RTKs), such as
      epidermal growth factor receptor (EGFR), fibroblast growth factor receptor
      (FGFR), vascular endothelial growth factor receptor (VEGFR) and platelet-derived
      growth factor receptor (PDGFR), also play key roles in the development and
      progression of many types of tumors. It has been realized that TGF-beta signaling
      and RTK pathways interact with each other and their interplay is important for
      cancer development. They are mutually regulated and cooperatively modulate cell
      survival and migration, epithelial-mesenchymal transition, and tumor
      microenvironment to accelerate tumorigenesis and tumor metastasis. RTKs can
      modulate Smad-dependent transcription or cooperate with TGF-beta to potentiate
      its oncogenic activity, while TGF-beta signaling can in turn control RTK
      signaling by regulating their activities or expression. This review summarizes
      current understandings of the interplay between TGF-beta signaling and RTKs and
      its influence on tumor development.

PMID- 29067650
TI  - CKD complications in kidney-transplanted patients going back to dialysis: impact
      on patients outcomes.
AB  - AIMS: The management of chronic kidney disease (CKD) complications is not always
      adequate in patients with a failed kidney transplant. We aimed to evaluate the
      frequency of CKD complications and assess whether they may lead to worse outcomes
      in this patient population. METHOD: We analyzed 49 kidney transplant recipients
      with a failed transplant (T+) and matched non-transplanted patients (T-) starting
      dialysis between 2000 and 2010 in five dialysis centers in France. CKD
      complications at dialysis initiation, hospitalizations and death were recorded
      and compared between the two groups. RESULTS: At dialysis initiation, T+ patients
      were more likely to have bicarbonate < 22 mmol/l (77.6 vs. 22.0%, p < 0.01),
      phosphate > 1.5 mmol/l (77.6 vs. 59.2%, p = 0.03), arterial blood pressure >
      130/80 mmHg (75.5 vs. 93.9%, p = 0.01), body mass index < 23 (59.2 vs. 32.7%, p =
      0.01) and albumin < 38 g/l (69.4 vs. 36.7%) than T- patients. T+ patients were
      hospitalized more frequently in the year following dialysis initiation (40.8 +/-
      7.0 vs. 16.3 +/- 5.3%, log rank p = 0.01) and 5-year survival rate was lower than
      in T- patients (82.1 +/- 6.2 vs. 64.0 +/- 7.4%, log rank p = 0.02). However risk
      of hospitalization and mortality was lesser after adjustments for CKD
      complications. CONCLUSION: Despite regular follow-up by nephrologists, CKD
      complications before initiation of dialysis are more frequent in T+ patients than
      in T- patients. A better management of CKD complications in T+ patients could
      improve outcomes after dialysis initiation.

PMID- 29067652
TI  - An Overview of Recent Therapeutics Advances for Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy
      in childhood. Mutations of the DMD gene destabilize the dystrophin associated
      glycoprotein complex in the sarcolemma. Ongoing mechanical stress leads to
      unregulated influx of calcium ions into the sarcoplasm, with activation of
      proteases, release of proinflammatory cytokines, and mitochondrial dysfunction.
      Cumulative damage and reparative failure leads to progressive muscle necrosis,
      fibrosis, and fatty replacement. Although there is presently no cure for DMD,
      scientific advances have led to many potential disease-modifying treatments,
      including dystrophin replacement therapies, upregulation of compensatory
      proteins, anti-inflammatory agents, and other cellular targets. Recently approved
      therapies include ataluren for stop codon read-through and eteplirsen for exon 51
      skipping of eligible individuals. The purpose of this chapter is to summarize the
      clinical features of DMD, to describe current outcome measures used in clinical
      studies, and to highlight new emerging therapies for affected individuals.

PMID- 29067651
TI  - Interventions to Improve Management of Chronic Conditions Among Racial and Ethnic
      Minorities.
AB  - Digital and mhealth interventions can be effective in improving health outcomes
      among minority patients with diabetes, congestive heart failure, and chronic
      respiratory diseases. A number of electronic and digital approaches to individual
      and population-level interventions involving telephones, internet and web-based
      resources, and mobile platforms have been deployed to improve chronic disease
      outcomes. This paper summarizes the evidence supporting the efficacy of various
      behavioral and digital interventions targeting intermediate outcomes and
      hospitalizations with particular emphasis on studies examining the effects of
      these interventions on racial and ethnic minority population.

PMID- 29067653
TI  - Clinical Manifestations and Overall Management Strategies for Duchenne Muscular
      Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that causes
      progressive weakness and wasting of skeletal muscular and myocardium in boys due
      to mutation of dystrophin. The structural integrity of each individual skeletal
      and cardiac myocyte is significantly compromised upon physical stress due to the
      absence of dystrophin. The progressive destruction of systemic musculature and
      myocardium causes affected patients to develop multiple organ disabilities,
      including loss of ambulation, physical immobility, neuromuscular scoliosis, joint
      contracture, restrictive lung disease, obstructive sleep apnea, and
      cardiomyopathy. There are some central nervous system-related medical problems,
      as dystrophin is also expressed in the neuronal tissues. Although principal
      management is to mainly delay the pathological process, an enhanced understanding
      of underlying pathological processes has significantly improved quality of life
      and longevity for DMD patients. Future research in novel molecular approach is
      warranted to answer unanswered questions.

PMID- 29067654
TI  - Cardiac Involvement in Duchenne Muscular Dystrophy and Related
      Dystrophinopathies.
AB  - Dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular
      dystrophy (BMD), X-linked dilated cardiomyopathy (XLCM), and facioscapulohumeral
      muscular dystrophy (FSHD). DMD/BMD are X-linked recessive disorders, related to
      the synthesis of dystrophin. Most of DMD after the third decade of their age
      develop cardiomyopathy that remains silent, due to relative physical inactivity.
      Cardiac disease in female carriers presents with hypertrophy, arrhythmias or
      dilated cardiomyopathy, clinically overt by increasing age.In ECG, DMD presents
      increased R/S ratio in the right precordial leads, deep Q waves in the lateral
      leads, conduction abnormalities, and arrhythmias. Echocardiography, although
      widely available and inexpensive, is highly depended on the acoustic window and
      operator's experience. Tissue Doppler can be used to identify early changes of
      cardiomyopathy and detect progressive cardiac damage. CMR, a noninvasive,
      nonradiating technique, by evaluation of cardiac volumes, mass, ejection
      fraction, inflammation, and fibrosis, is ideal for early diagnosis. Subepicardial
      fibrosis in the inferolateral wall is the typical CMR lesion in DMD/BMD.Early
      initiation of angiotensin converting enzyme inhibitors (ACEI) treatment, such as
      perindopril, was associated with lower mortality in DMD with normal LV ejection
      fraction at study entry. Other studies documented that a beta-blocker (BB), in
      addition to ACEI, improves LV systolic function in MD. These encouraging results
      recommend initiation of ACEI and/or BB early after diagnosis of the muscular
      dystrophy, especially in DMD.

PMID- 29067655
TI  - Characterization of the Inflammatory Response in Dystrophic Muscle Using Flow
      Cytometry.
AB  - Although mutations of the dystrophin gene are the causative defect in Duchenne
      muscular dystrophy (DMD) patients, secondary disease processes such as
      inflammation contribute greatly to the pathogenesis of DMD. Genetic and
      histological studies have shown that distinct facets of the immune system promote
      muscle degeneration or regeneration during muscular dystrophy through mechanisms
      that are only beginning to be defined. Although histological methods have allowed
      the enumeration and localization of immune cells within dystrophic muscle, they
      are limited in their ability to assess the full spectrum of phenotypic states of
      an immune cell population and its functional characteristics. This chapter
      highlights flow cytometry methods for the isolation and functional study of
      immune cell populations from muscle of the mdx mouse model of DMD. We include a
      detailed description of preparing single-cell suspensions of dystrophic muscle
      that maintain the integrity of cell-surface markers used to identify macrophages,
      eosinophils, group 2 innate lymphoid cells, and regulatory T cells. This method
      complements the battery of histological assays that are currently used to study
      the role of inflammation in muscular dystrophy, and provides a platform capable
      of being integrated with multiple downstream methodologies for the mechanistic
      study of immunity in muscle degenerative diseases.

PMID- 29067656
TI  - Imaging Analysis of the Neuromuscular Junction in Dystrophic Muscle.
AB  - Duchenne muscular dystrophy (DMD), caused by the absence of the protein
      dystrophin, is characterized as a neuromuscular disease in which muscle weakness,
      increased susceptibility to muscle injury, and inadequate repair appear to
      underlie the pathology. Considerable attention has been dedicated to studying
      muscle fiber damage, but there is little information to determine if damage from
      contraction-induced injury also occurs at or near the nerve terminal axon.
      Interestingly, both human patients and the mouse model for DMD (the mdx mouse)
      present fragmented neuromuscular junction (NMJ) morphology. Studies of mdx mice
      have revealed presynaptic and postsynaptic abnormalities, nerve terminal
      discontinuity, as well as increased susceptibility of the NMJ to contraction
      induced injury with corresponding functional changes in neuromuscular
      transmission and nerve-evoked electromyography. Focusing on the NMJ as a
      contributor to functional deficits in the muscle represents a paradigm shift from
      the more prevalent myocentric perspectives. Further studies are needed to
      determine the extent to which the nerve-muscle interaction is disrupted in DMD
      and the role of the NMJ in the dystrophic progression. This chapter lists the
      tools needed for nerve terminal and NMJ structural analysis using fluorescence
      imaging, and provides a step-by-step outline for how to stain, image, and analyze
      the NMJ in skeletal muscle, with specific attention to mdx muscle.

PMID- 29067657
TI  - System Biology Approach: Gene Network Analysis for Muscular Dystrophy.
AB  - Phenotypic changes at different organization levels from cell to entire organism
      are associated to changes in the pattern of gene expression. These changes
      involve the entire genome expression pattern and heavily rely upon correlation
      patterns among genes. The classical approach used to analyze gene expression data
      builds upon the application of supervised statistical techniques to detect genes
      differentially expressed among two or more phenotypes (e.g., normal vs. disease).
      The use of an a posteriori, unsupervised approach based on principal component
      analysis (PCA) and the subsequent construction of gene correlation networks can
      shed a light on unexpected behaviour of gene regulation system while maintaining
      a more naturalistic view on the studied system.In this chapter we applied an
      unsupervised method to discriminate DMD patient and controls. The genes having
      the highest absolute scores in the discrimination between the groups were then
      analyzed in terms of gene expression networks, on the basis of their mutual
      correlation in the two groups. The correlation network structures suggest two
      different modes of gene regulation in the two groups, reminiscent of important
      aspects of DMD pathogenesis.

PMID- 29067658
TI  - Proteomic Profiling of the Dystrophin-Deficient Brain.
AB  - Duchenne muscular dystrophy is a highly progressive neuromuscular disorder caused
      by primary abnormalities in the Dmd gene encoding the membrane cytoskeletal
      protein dystrophin. Dystrophinopathies are multi-systems disorders that are
      characterized by severe skeletal muscle wasting, with loss of independent
      ambulation in the early teenage years, followed by cardio-respiratory
      complications and premature death. Nonprogressive cognitive impairments are
      estimated to affect approximately one-third of dystrophic children. To identify
      the molecular mechanisms behind the impaired brain function in dystrophinopathy,
      liquid chromatography-based mass spectrometry offers an unbiased and technology
      driven approach. In this chapter, we give a detailed description of a label-free
      mass spectrometric method to investigate proteome-wide changes in the dystrophin
      deficient brain from a genetic mouse model of Duchenne muscular dystrophy.

PMID- 29067659
TI  - Probing the Pathogenesis of Duchenne Muscular Dystrophy Using Mouse Models.
AB  - Investigations using mouse models have provided seminal insights into the
      pathogenesis of Duchenne muscular dystrophy and the development of novel
      therapeutics. Several important methods have been considered standard-in-the
      field for analyses of skeletal muscle weakness, strength, endurance, and
      histopathology, as well as responses to therapeutics such as glucocorticoids,
      disease modifying drugs which are part of the current standard of care for
      patients with this disease. Here we describe optimized genetic, genomic, and
      physiologic assays to probe dystrophic pathobiology in the mdx mouse and related
      strains.

PMID- 29067660
TI  - Exon Skipping Therapy Using Phosphorodiamidate Morpholino Oligomers in the mdx52
      Mouse Model of Duchenne Muscular Dystrophy.
AB  - Exon skipping therapy using synthetic DNA-like molecules called antisense
      oligonucleotides (ASOs) is a promising therapeutic candidate for overcoming the
      dystrophin mutation that causes Duchenne muscular dystrophy (DMD). This treatment
      involves splicing out the frame-disrupting segment of the dystrophin mRNA, which
      restores the reading frame and produces a truncated yet functional dystrophin
      protein. Phosphorodiamidate morpholino oligomer (PMO) is the safest ASO for
      patients among ASOs and has recently been approved under the accelerated approval
      pathway by the U.S. Food and Drug Administration (FDA) as the first drug for DMD.
      Here, we describe the methodology and protocol of PMO transfection and evaluation
      of the exon skipping efficacy in the mdx52 mouse, an exon 52 deletion model of
      DMD produced by gene targeting. The mdx52 mouse model offers advantages over the
      mdx mouse, a spontaneous DMD model with a nonsense mutation in exon 23, in terms
      of the deletion in a hotspot of deletion mutations in DMD patients, the analysis
      of caveolae and also Dp140 and Dp260, shorter dystrophin isoforms.

PMID- 29067661
TI  - Designing Effective Antisense Oligonucleotides for Exon Skipping.
AB  - During the past 10 years, antisense oligonucleotide-mediated exon skipping and
      splice modulation have proven to be powerful tools for correction of mRNA
      splicing in genetic diseases. In 2016, the US Food and Drug Administration (FDA)
      approved Exondys 51 (eteplirsen) and Spinraza (nusinersen), the first exon
      skipping and exon inclusion drugs, to treat patients with Duchenne muscular
      dystrophy (DMD) and spinal muscular atrophy (SMA), respectively. The exon
      skipping of DMD mRNA aims to restore the disrupted reading frame using antisense
      oligonucleotides (AONs), allowing the production of truncated but partly
      functional dystrophin proteins, and slow down the progression of the disease.
      This approach has also been explored in several other genetic disorders,
      including laminin alpha2 chain-deficient congenital muscular dystrophy, dysferlin
      deficient muscular dystrophy (e.g., Miyoshi myopathy and limb-girdle muscular
      dystrophy type 2B), sarcoglycanopathy (limb-girdle muscular dystrophy type 2C),
      and Fukuyama congenital muscular dystrophy. Antisense-mediated exon skipping is
      also a powerful tool to examine the function of genes and exons. A significant
      challenge in exon skipping is how to design effective AONs. The mechanism of mRNA
      splicing is highly complex with many factors involved. The selection of target
      sites, the length of AONs, the AON chemistry, and the melting temperature versus
      the RNA strand play important roles. A cocktail of AONs can be employed to skip
      multiples exons. In this chapter, we discuss the design of effective AONs for
      exon skipping.

PMID- 29067662
TI  - Identification of Splicing Factors Involved in DMD Exon Skipping Events Using an
      In Vitro RNA Binding Assay.
AB  - Mutation-induced exon skipping in the DMD gene can modulate the severity of the
      phenotype in patients with Duchenne or Becker Muscular Dystrophy. These
      alternative splicing events are most likely the result of changes in recruitment
      of splicing factors at cis-acting elements in the mutated DMD pre-mRNA. The
      identification of proteins involved can be achieved by an affinity purification
      procedure. Here, we provide a detailed protocol for the in vitro RNA binding
      assay that we routinely apply to explore molecular mechanisms underlying splicing
      defects in the DMD gene. In vitro transcribed RNA probes containing either the
      wild type or mutated sequence are oxidized and bound to adipic acid dihydrazide
      agarose beads. Incubation with a nuclear extract allows the binding of nuclear
      proteins to the RNA probes. The unbound proteins are washed off and then the
      specifically RNA-bound proteins are released from the beads by an RNase
      treatment. After separation by SDS-PAGE, proteins that display differential
      binding affinities for the wild type and mutant RNA probes are identified by mass
      spectrometry.

PMID- 29067663
TI  - The Use of Antisense Oligonucleotides for the Treatment of Duchenne Muscular
      Dystrophy.
AB  - Antisense oligonucleotides (AONs) hold great promise for therapeutic splice
      switching correction in many genetic diseases and in particular for Duchenne
      muscular dystrophy (DMD), where AONs can be used to reframe the dystrophin
      transcript and give rise to a partially deleted but yet functional dystrophin
      protein. Many different chemistries of AONs can be used for splice switching
      modulation, and some of them have been evaluated in clinical trials for DMD.
      However, despite advances in AON chemistry and design, systemic use of AONs is
      limited due to poor tissue uptake, and sufficient therapeutic efficacy is
      difficult to achieve. Therefore, there is still a critical need to develop
      efficient AONs able to restore the expression of dystrophin in all relevant
      tissues and international efforts are currently on going to develop new compounds
      or alternative chemistries with higher therapeutic potential. Here, we describe
      the methods to evaluate the potency of antisense oligonucleotides, and in
      particular of tricyclo-DNA (tcDNA)-AONs, a novel class of AONs which displays
      unique pharmacological properties and unprecedented uptake in many tissues after
      systemic administration. We focus on the most widely used mouse model for DMD,
      the mdx mouse and detail methods to analyze the skipping of the mouse exon 23
      both in vitro in H2K mdx cells and in vivo in the mdx mouse model.

PMID- 29067664
TI  - PMO Delivery System Using Bubble Liposomes and Ultrasound Exposure for Duchenne
      Muscular Dystrophy Treatment.
AB  - Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by
      progressive muscle degeneration, caused by nonsense or frameshift mutations in
      the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce
      specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO)
      has been approved for clinical use in DMD. However, an efficient PMO delivery
      strategy is required to improve the therapeutic efficacy in DMD patients. We
      previously developed polyethylene glycol (PEG)-modified liposomes containing
      ultrasound contrast gas, "Bubble liposomes" (BLs), and found that the combination
      of BLs with ultrasound exposure is a useful gene delivery tool. Here, we describe
      an efficient PMO delivery strategy using the combination of BLs and ultrasound
      exposure to treat muscles in a DMD mouse model (mdx). This ultrasound-mediated BL
      technique can increase the PMO-mediated exon-skipping efficiency, leading to
      significantly increased dystrophin expression. Thus, the combination of BLs and
      ultrasound exposure may be a feasible PMO delivery method to improve therapeutic
      efficacy and reduce the PMO dosage for DMD treatment.

PMID- 29067665
TI  - Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy-Based Analysis of Lipid
      Components in Serum/Plasma of Patients with Duchenne Muscular Dystrophy (DMD).
AB  - Proton nuclear magnetic resonance spectroscopy (1H NMR) is a useful tool for the
      analysis of lipid components in biofluids such as serum/plasma. Such tool is
      applied for the analysis of lipid components in serum/plasma of patients with
      Duchenne muscular dystrophy (DMD). The practical approach of sampling, storage,
      lipid extraction procedure, sample preparation before performing the 1H NMR
      spectroscopy experiments is presented. All the experimental parameters of NMR
      spectroscopy are also described. Details of the assignments of lipid components
      (qualitative analysis) and quantification of particular lipid components
      (quantitative analysis) are explained.

PMID- 29067666
TI  - Test of Antifibrotic Drugs in a Cellular Model of Fibrosis Based on Muscle
      Derived Fibroblasts from Duchenne Muscular Dystrophy Patients.
AB  - An in vitro model of muscle fibrosis, based on the use of primary human
      fibroblasts isolated from muscle biopsies of patients affected by Duchenne
      muscular dystrophies (DMD) and cultivated in monolayer and 3D conditions, is used
      to test the potential antifibrotic activity of pirfenidone (PFD). This in vitro
      model may be usefully also to evaluate the toxicity and efficacy of other
      candidate molecules for the treatment of fibrosis. The drug toxicity is evaluated
      using a colorimetric assay based on the conversion of tetrazolium salt (MTT) to
      insoluble formazan, while the effect of the drug on cell proliferation is
      measured with the bromodeoxyuridine incorporation assay. The efficacy of the drug
      is evaluated in fibroblast monolayers by quantitating synthesis and deposition of
      intracellular collagen with a spectrophotometric picrosirius red-based assay, and
      by quantitating cell migration using a "scratch" assay. The efficacy of PFD as
      antifibrotic drug is also evaluated in a 3D fibroblast model by measuring
      diameters and number of nodules.

PMID- 29067667
TI  - Flow Cytometry-Defined CD49d Expression in Circulating T-Lymphocytes Is a
      Biomarker for Disease Progression in Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) affects 1:3500-1:5000 male births, and is
      caused by X-linked mutations in the dystrophin gene, manifested by progressive
      muscle weakness and wasting due to the absence of dystrophin protein, leading to
      degeneration of skeletal muscle. DMD patients are clinically heterogeneous and
      the functional phenotype often cannot be correlated with the genotype. Therefore,
      defined reliable noninvasive biomarkers aiming at predicting if a given DMD child
      will progress more or less rapidly will be instrumental to better design
      inclusion of defined patients for future therapeutic assays. We recently showed
      that CD49d expression levels in blood-derived T-cell subsets can predict disease
      progression in DMD patients. Herein we describe in detail the methodology to be
      applied for defining, through four-color flow cytometry, the membrane expression
      levels of the CD49d (the alpha4 chain of the integrins alpha4beta1 and
      alpha4beta7) in circulating CD4+ and CD8+ T cell subsets. Since we have also
      shown that this molecule can also be placed as a potential target for
      therapeutics in DMD, we also describe the cell migration functional assay that
      can be applied to test potential CD49d inhibitors that can modulate their ability
      to cross endothelial or extracellular matrix (ECM) barriers.

PMID- 29067668
TI  - Advanced Methods to Study the Cross Talk Between Fibro-Adipogenic Progenitors and
      Muscle Stem Cells.
AB  - Functional interactions between muscle (satellite) stem cells-MuSCs-and other
      cellular components of their niche (the fibro-adipogenic progenitors-FAPs)
      coordinate regeneration of injured as well as diseased skeletal muscles. These
      interactions are largely mediated by secretory networks, whose integrity is
      critical to determine whether repair occurs by compensatory regeneration leading
      to formation of new contractile fibers, or by maladaptive formation of fibrotic
      scars and fat infiltration. Here we provide the description of methods for
      isolation of FAPs and MuSCs from muscles of wild type and dystrophic mice, and
      protocols of cocultures as well as MuSC's exposure to FAP- derived exosomes.
      These methods and protocols can be exploited in murine models of acute muscle
      injury to investigate salient features of physiological repair, and in models of
      muscular diseases to identify dysregulated networks that compromise functional
      interactions between cellular components of the regeneration environment during
      disease progression. We predict that exporting these procedures to patient
      derived muscle samples will contribute to advance our understanding of human
      skeletal myogenesis and related disorders.

PMID- 29067669
TI  - AAV6 Vector Production and Purification for Muscle Gene Therapy.
AB  - Vectors derived from adeno-associated viruses (AAV) have been generated using
      numerous naturally occurring and synthetic serotypes of the virus. Such vectors
      have proven to be extremely useful for a variety of gene transfer studies, both
      in vitro and in vivo, and are increasingly being used in gene therapy protocols
      for a variety of human disorders. Methods to produce AAV vectors typically rely
      on co-transfection of several different plasmid vectors that carry the transgene
      of interest (the gene to be delivered , in a "transfer plasmid") and helper genes
      needed for AAV vector replication and packaging (helper plasmids). While the
      methods used to generate AAV are conceptually simple, minor variations in a
      variety of steps can result in significant differences in the overall yield of
      vector. Here we describe protocols for generating vectors derived from AAV6,
      which are particularly useful for gene transfer to muscle tissues.

PMID- 29067670
TI  - From gRNA Identification to the Restoration of Dystrophin Expression: A
      Dystrophin Gene Correction Strategy for Duchenne Muscular Dystrophy Mutations
      Using the CRISPR-Induced Deletion Method.
AB  - The discovery of the CRISPR-Cas9 system raises hope for the treatment of many
      genetic disorders. We describe here an approach based on the use of a pair of
      single guide RNAs to form a hybrid exon that does not only restore the dystrophin
      gene reading frame but also results in the production of a dystrophin protein
      with an adequate structure of the central rod-domain, with a correct spectrin
      like repeat. The therapeutic approach described here involved DMD patient cells
      having a deletion of exons 51-53 of the DMD gene.

PMID- 29067672
TI  - Differentiating between mixed-effects and latent-curve approaches to growth
      modeling.
AB  - In psychology, mixed-effects models and latent-curve models are both widely used
      to explore growth over time. Despite this widespread popularity, some confusion
      remains regarding the overlap of these different approaches. Recent articles have
      shown that the two modeling frameworks are mathematically equivalent in many
      cases, which is often interpreted to mean that one's choice of modeling framework
      is merely a matter of personal preference. However, some important differences in
      estimation and specification can lead to the models producing very different
      results when implemented in software. Thus, mathematical equivalence does not
      necessarily equate to practical equivalence in all cases. In this article, we
      discuss these two common approaches to growth modeling and highlight contexts in
      which the choice of the modeling framework (and, consequently, the software) can
      directly impact the model estimates, or in which certain analyses can be
      facilitated in one framework over the other. We show that, unless the data are
      pristine, with a large sample size, linear or polynomial growth, and no missing
      data, and unless the participants have the same number of measurements collected
      at the same set of time points, one framework is often more advantageous to
      adopt. We provide several empirical examples to illustrate these situations, as
      well as ample software code so that researchers can make informed decisions
      regarding which framework will be the most beneficial and most straightforward
      for their research interests.

PMID- 29067673
TI  - A few remarks on spatial interference in visual stimuli.
AB  - Many vision experiments, e.g., tests of masking and visual crowding, involve the
      effect of adding a second stimulus to an initial one. The effects of such
      additions are generally considered in terms of physiological mechanisms and the
      possibility of interference in the stimuli is generally not considered. In the
      present study, interference between two stimuli was assessed by comparing the sum
      of amplitudes in the combined stimulus to the sums of the amplitudes in the two
      stimuli determined separately. With this approach, evidence for interference was
      found. It was also found that adding a second stimulus may alter the phase
      angles. These observations mean that the same stimulus presented together with
      other stimuli may have less stimulus power than when presented by itself. Thus,
      it is necessary to take account of the possibility of interference when
      interpreting results from experiments in which the effect of one stimulus element
      upon another is explored.

PMID- 29067671
TI  - A Review of Asenapine in the Treatment of Bipolar Disorder.
AB  - Bipolar disorder places a significant burden on the affected individuals, their
      family, healthcare systems and the overall economy. More treatment options are
      needed, especially those with better efficacy and tolerability. Asenapine is a
      second-generation antipsychotic approved in Europe (brand name Sycrest(r)) for
      the treatment of moderate-to-severe manic episodes associated with bipolar I
      disorder in adults, and in the US (brand name Saphris(r)) for the treatment of
      manic or mixed episodes of bipolar I disorder in adults and children aged 10-17
      years. It is the antagonistic activity at the D2 receptor that is likely
      responsible for the antimanic properties of asenapine. Clinical trials have
      demonstrated that asenapine mono- and add-on therapy is effective in the short-
      and long-term treatment of mania associated with bipolar I disorder in adult and
      paediatric patients. In addition, post hoc and pooled data analyses have shown
      that asenapine is effective in reducing clinically significant depressive
      symptoms in patients with bipolar I disorder. The most common adverse events
      associated with asenapine are somnolence, dizziness, extrapyramidal symptoms,
      increased bodyweight and oral hypoesthesia. However, the incidence of these
      events, particularly weight gain, is generally lower than with olanzapine. In one
      study, asenapine has been shown to improve health-related quality of life.
      Economic analyses indicate that the use of asenapine can, over time, lead to a
      reduction in the costs of treatment.

PMID- 29067674
TI  - Delivery of Biologics Across the Blood-Brain Barrier with Molecular Trojan Horse
      Technology.
AB  - Biologics are potential new therapeutics for many diseases of the central nervous
      system. Biologics include recombinant lysosomal enzymes, neurotrophins, decoy
      receptors, and therapeutic antibodies. These are large molecule drugs that do not
      cross the blood-brain barrier (BBB). All classes of biologics have been tested,
      without success, in clinical trials of brain disease over the last 25 years. In
      none of these past clinical trials was the biologic re-engineered to enable
      transport across the BBB. If the biologic does not cross the BBB, the drug cannot
      reach the target site in brain, and success in a clinical trial is not expected.
      Biologics can be re-engineered for BBB transport with the use of molecular Trojan
      horse technology. A BBB molecular Trojan horse is a monoclonal antibody (MAb)
      against an endogenous BBB receptor transporter, such as the insulin receptor or
      transferrin receptor. The receptor-specific MAb penetrates the brain via
      transport on the endogenous BBB receptor. The MAb acts as a molecular Trojan
      horse to deliver across the BBB the biologic pharmaceutical that is genetically
      fused to the MAb. The lead Trojan horse is a MAb against the human insulin
      receptor (HIR), and HIRMAb-derived fusion proteins have entered clinical trials
      for the treatment of brain disease.

PMID- 29067675
TI  - Estimating medial gastrocnemius muscle volume in children with spastic cerebral
      palsy: a cross-sectional investigation.
AB  - AIM: This cross-sectional investigation evaluates the reliability of estimating
      medial gastrocnemius anatomical cross-sectional area (aCSA) in typically
      developing and spastic cerebral palsy (SCP) cohorts. It verifies whether muscle
      volume estimations based on aCSA improve when aCSA is multiplied by muscle-tendon
      unit (MTU) or muscle length, and whether the resulting errors in volume
      estimations are smaller than changes after intervention. METHOD: Fifteen
      typically developing children (mean age 8y 2mo [SD 1y 5mo], six males, nine
      females) and 30 children with SCP (mean age 9y 2mo [SD 2y 5mo], 22 males, eight
      females, Gross Motor Function Classification System [GMFCS] level I=15, II=15)
      participated in the investigation. The SCP cohort was divided according to GMFCS
      level. A three-dimensional freehand ultrasound technique was used to estimate
      medial gastrocnemius aCSA, muscle volume, MTU, and muscle length. Estimated
      muscle volume (aCSA*MTU or muscle length) was compared with the measured muscle
      volume. RESULTS: Anatomical cross-sectional area, muscle volume, and muscle
      length significantly differed between the typically developing and two SCP
      cohorts (p<=0.050). aCSA multiplied by either MTU or muscle length improved
      estimations of medial gastrocnemius volume. Leave-one-out cross-validation
      revealed an absolute difference with measured muscle volume of 3.77 ml (SD 2.90).
      INTERPRETATION: This investigation revealed that medial gastrocnemius muscle
      volume can be reliably estimated in a clinically feasible manner in typically
      developing children and those with SCP. WHAT THIS PAPER ADDS: Medial
      gastrocnemius anatomical cross-sectional area (aCSA) can be reliably estimated in
      children with spastic cerebral palsy. The location of the anatomical cross
      section should be taken with respect to muscle and not bone length. Medial
      gastrocnemius volume can be reliably estimated by multiplying aCSA and muscle
      length. The errors in volume estimations are smaller than reported differences
      after interventions.

PMID- 29067676
TI  - Myc binding protein 2 suppresses M2-like phenotypes in macrophages during zymosan
      induced inflammation in mice.
AB  - MYCBP2 is an E3 ubiquitin ligase, which is well characterized as a key element in
      the inhibition of neuronal growth, synapse formation and synaptic strength by
      regulating several signaling pathways. Although MYCBP2 was suspected to be
      expressed also in immune cells, to date nothing is known about its role in
      inflammation. We used Multi-epitope ligand cartography (MELC), a method for
      multiple sequential immunohistology, to show that MYCBP2 is strongly expressed in
      monocyte-derived macrophages during zymosan-induced inflammation. We generated a
      myeloid-specific knockout mouse and found that loss of MYCBP2 in myeloid cells
      reduced nociceptive (painful) behavior during the resolution phase (1-3 days
      after zymosan injection). Quantitative MELC analyses and flow cytometric analysis
      showed an increased number of CD206-expressing macrophages in the inflamed paw
      tissue. Fittingly, CD206 and arginase 1 expression was upregulated in MYCBP2
      deficient bone marrow-derived macrophages after polarization with IL10 or IL4.
      The regulation of protein expression in these macrophages by MYCBP2 varied
      depending on the polarization signal. The increased IL10-induced CD206 expression
      in MYCBP2-deficient macrophages was mediated by p38 MAPK, while IL4-induced CD206
      expression in MYCBP2-deficient macrophages was mediated by protein kinase A.

PMID- 29067677
TI  - Yeast glycolipid biosurfactants.
AB  - Various yeasts, both conventional and exotic ones, are known to produce compounds
      useful to mankind. Ethanol is the most known of these compounds, but more complex
      molecules such as amphiphilic biosurfactants can also be derived from eukaryotic
      microorganisms at an industrially and commercially relevant scale. Among them,
      glycolipids are the most promising, due to their attractive properties and high
      product titers. Many of these compounds can be considered as secondary
      metabolites with a specific function for the host. Hence, a dedicated
      biosynthetic process enables regulation and combines pathways delivering the
      lipidic moiety and the hydrophilic carbohydrate part of the glycolipid. In this
      Review, we will discuss the biosynthetic and regulatory aspects of the yeast
      derived sophorolipids, mannosylerythritol lipids, and cellobiose lipids, with
      special emphasis on the relation between glycolipid synthesis and the general
      lipid metabolism.

PMID- 29067678
TI  - The immunoproteasome subunit LMP7 is required in the murine thymus for filling up
      a hole in the T cell repertoire.
AB  - Cells of hematopoietic origin express high levels of the immunoproteasome, a
      cytokine-inducible variant of the proteasome which has been implicated in
      regulating inflammatory responses and antigen presentation. In the thymus,
      medullary thymic epithelial cells (mTECs) and cortical thymic epithelial cells
      (cTECs) do express different proteasome subunits exerting chymotrypsin-like
      activities suggesting distinct functions in thymic T cell selection. Employing
      the lymphocytic choriomeningitis virus (LCMV) infection model, we could show that
      the immunoproteasome subunit LMP7 was absolutely required for the generation of
      LCMV GP118-125 -specific T cells although the class I mediated presentation of
      GP118-125 was not dependent on LMP7. Using bone marrow chimeras and adoptive
      transfer of LMP7-deficient CD8+ T cells into RAG1-deficient mice we show that
      LMP7-deficient mice lacked GP118-125 -specific T cell precursors and that LMP7
      was required in radioresistant cells - most likely thymic epithelial cells - to
      enable their selection. Since LMP7 is strongly expressed in negatively selecting
      mTECs but barely in positively selecting cTECs our data suggest that LMP7 was
      required to avoid excessive negative selection of GP118-125 -specific T cell
      precursors. Taken together, this study demonstrates that the immunoproteasome is
      a crucial factor for filling up holes within the cytotoxic T cell repertoire.

PMID- 29067679
TI  - Maternal morbidity after implementation of a postpartum hemorrhage protocol
      including use of misoprostol.
AB  - OBJECTIVE: To compare maternal morbidity before and after implementation of a
      postpartum hemorrhage (PPH) protocol that included misoprostol. METHODS: A
      retrospective analysis was performed using data from 34 631 deliveries recorded
      at a Spanish hospital between January 1, 2007, and December 31, 2014. The PPH
      protocol was implemented in 2009 and included use of misoprostol and the Bakri
      balloon. RESULTS: The pre-implementation and post-implementation groups comprised
      9394 and 25 237 women, respectively. Women in the pre-implementation group tended
      to have lower hemoglobin levels than did those in the post-implementation group:
      811 (8.6%) versus 1349 (5.3%) for levels less than 90 g/L, and 272 (2.9%) versus
      497 (2.0%) for levels less than 80 g/L (both P<0.001). Implementation of the PPH
      protocol was also associated with a decrease in the frequency of postpartum
      hysterectomies owing to uterine atony (0.11 cases per 1000 deliveries vs 0.53
      cases per 1000 deliveries for the pre-implementation group; P=0.063). Pregnancy
      length, maternal age, neonatal weight at delivery, multiple pregnancy, previous
      cesarean delivery, parity, operative vaginal delivery, induced labor, cesarean
      delivery, and not using the PPH protocol were found to predict postpartum anemia
      in the multivariate analysis (all P<0.001). CONCLUSION: Implementation of the PPH
      protocol decreased rates of postpartum anemia and postpartum hysterectomy owing
      to uterine atony.

PMID- 29067680
TI  - Cryptic lineage diversity, body size divergence, and sympatry in a species
      complex of Australian lizards (Gehyra).
AB  - Understanding the joint evolutionary and ecological underpinnings of sympatry
      among close relatives remains a key challenge in biology. This problem can be
      addressed through joint phylogenomic and phenotypic analysis of complexes of
      closely related lineages within, and across, species and hence representing the
      speciation continuum. For a complex of tropical geckos from northern Australia
      Gehyra nana and close relatives-we combine mtDNA phylogeography, exon-capture
      sequencing, and morphological data to resolve independently evolving lineages and
      infer their divergence history and patterns of morphological evolution. Gehyra
      nana is found to include nine divergent lineages and is paraphyletic with four
      other species from the Kimberley region of north-west Australia. Across these 13
      taxa, 12 of which are restricted to rocky habitats, several lineages overlap
      geographically, including on the diverse Kimberley islands. Morphological
      evolution is dominated by body size shifts, and both body size and shape have
      evolved gradually across the group. However, larger body size shifts are observed
      among overlapping taxa than among closely related parapatric lineages of G. nana,
      and sympatric lineages are more divergent than expected at random. Whether
      elevated body size differences among sympatric lineages are due to ecological
      sorting or character displacement remains to be determined.

PMID- 29067681
TI  - Chitosan-triclosan particles modulate inflammatory signaling in gingival
      fibroblasts.
AB  - BACKGROUND AND OBJECTIVES: An important goal of periodontal therapy is the
      modulation of the inflammatory response. To this end, several pharmacological
      agents have been evaluated. Triclosan corresponds to an antibacterial and anti
      inflammatory agent currently used in periodontal therapy. Chitosan is a natural
      polymer that may act as a drug delivery agent and exerts antibacterial and anti
      inflammatory activities. Therefore, an association between both molecules might
      be useful to prevent inflammation and tissue destruction in periodontal tissues.
      MATERIAL AND METHODS: In the present study, we have generated chitosan-triclosan
      particles and evaluated their morphology, charge, biocompatibility and gene
      expression analysis in human gingival fibroblasts. RESULTS: The chitosan
      triclosan particles size and Z potential were 129 +/- 47 nm and 51 +/- 17 mV
      respectively. Human gingival fibroblast viability was not affected by chitosan
      triclosan. A total of 1533 genes were upregulated by interleukin (IL)-1beta. On
      the other hand, 943 were downregulated in fibroblasts stimulated with IL-1beta
      plus chitosan-triclosan particles. Fifty-one genes were identified as molecular
      targets upregulated by IL-1 beta and downregulated by the chitosan-triclosan
      particles. The gene ontology analysis revealed that these genes were enriched in
      categories related to biological processes, molecular function and cellular
      components. Furthermore, using real-time reverse transcription-polymerase chain
      reaction beta-actin, fibronectin, interleukin-6 and IL-1b genes were confirmed as
      targets upregulated by IL-1beta and downregulated by chitosan-triclosan
      particles. CONCLUSION: Our results show that chitosan-triclosan particles are
      able to modulate the inflammatory response in gingival fibroblasts. This effect
      might be useful in the prevention and/or treatment of inflammation in periodontal
      diseases.

PMID- 29067682
TI  - Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.
AB  - BACKGROUND: This is an updated version of the Cochrane Review published in the
      Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good
      prognosis, but up to 30% of people continue to have seizures despite several
      regimens of antiepileptic drugs. In this review, we summarized the current
      evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment
      for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and
      tolerability of ESL when used as an add-on treatment for people with drug
      resistant partial epilepsy. SEARCH METHODS: The searches for the original review
      were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group
      Specialized Register (6 December 2016), the Cochrane Central Register of
      Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016).
      There were no language restrictions. We reviewed the reference lists of retrieved
      studies to search for additional reports of relevant studies. We also contacted
      the manufacturers of ESL and experts in the field for information about any
      unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo controlled
      double-blind add-on trials of ESL in people with drug-resistant partial epilepsy.
      DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials
      for inclusion and extracted data. Outcomes investigated included 50% or greater
      reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse
      effects, and drug interactions. Primary analyses were by intention to treat
      (ITT). The dose-response relationship was evaluated in regression models. MAIN
      RESULTS: We included five trials (1799 participants) rated at low risk of bias;
      all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence
      interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI
      1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure
      frequency with an increase in efficacy with increasing doses of ESL. ESL was
      significantly associated with seizure freedom (RR 2.90, 95% CI 1.49 to 5.68).
      Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66,
      95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The
      following adverse effects were significantly associated with ESL: dizziness (RR
      2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR
      4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and
      vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was
      rated as moderate to high. AUTHORS' CONCLUSIONS: ESL reduces seizure frequency
      when used as an add-on treatment for people with drug-resistant partial epilepsy.
      The trials included in this review were of short-term duration and focused on
      adults. One new trial has been included in this update, but the conclusions are
      unchanged.

PMID- 29067683
TI  - Redesigning induction of labour processes.
AB  - BACKGROUND: An 'in-hours' birth represents a desired outcome following induction
      of labour (IOL) in terms of safety, efficiency and satisfaction. Women booked for
      IOL are often not commenced at their allocated times, and these sometimes complex
      births happen after-hours. AIMS: To measure the effect of an 11:00 hours
      commencement time for IOL. MATERIALS AND METHODS: A discrete-event-simulation
      patient-flow model was constructed. Multiple staffing and scheduling combinations
      were tested, before a brief pilot and subsequent introduction of a second IOL
      commencement time. A retrospective cohort study was performed using routinely
      collected data, comparing outcomes in two four-month time periods, before and
      after introduction of the new schedule. During Time Period A, women underwent
      cervical ripening at 19:00 hours and were reviewed the next morning for amniotomy
      and oxytocin infusion (ARM/oxytocin). During Time Period B, women were either
      admitted at 11:00 hours for cervical ripening followed by 23:00 hours
      ARM/oxytocin, or at 19:00 hours for cervical ripening followed by 06:00 hours
      ARM/oxytocin. The primary outcome measure was the likelihood of an in-hours birth
      (defined as 07:00-19:00 hours). RESULTS: In an analysis of 1689 women undergoing
      IOL, the new IOL booking schedule was associated with a 14.7% increase in in
      hours birth (68.4% vs 53.7%; P < 0.01), and a corresponding reduction in
      overnight births. Although the IOL to birth time was unaltered, we observed a
      decrease in IOL delays and admission-to-birth time, and a greater likelihood of
      vaginal birth within 24 h of admission. CONCLUSIONS: Introducing a 11:00 hours
      start-time for IOL has been associated with a significant increase in in-hours
      births.

PMID- 29067685
TI  - A possible link between KCNQ2- and STXBP1-related encephalopathies: STXBP1
      reduces the inhibitory impact of syntaxin-1A on M current.
AB  - OBJECTIVE: Kv7 channels mediate the voltage-gated M-type potassium current.
      Reduction of M current due to KCNQ2 mutations causes early onset epileptic
      encephalopathies (EOEEs). Mutations in STXBP1 encoding the syntaxin binding
      protein 1 can produce a phenotype similar to that of KCNQ2 mutations, suggesting
      a possible link between STXBP1 and Kv7 channels. These channels are known to be
      modulated by syntaxin-1A (Syn-1A) that binds to the C-terminal domain of the
      Kv7.2 subunit and strongly inhibits M current. Here, we investigated whether
      STXBP1could prevent this inhibitory effect of Syn-1A and analyzed the
      consequences of two mutations in STXBP1 associated with EOEEs. METHODS:
      Electrophysiologic analysis of M currents mediated by homomeric Kv7.2 or
      heteromeric Kv7.2/Kv7.3 channels in Chinese hamster ovary (CHO) cells
      coexpressing Syn-1A and/or STXBP1 or mutants STXBP1 p.W28* and p.P480L.
      Expression and interaction of these different proteins have been investigated
      using biochemical and co-immunoprecipitation experiments. RESULTS: Syn-1A
      decreased M currents mediated by Kv7.2 or Kv7.2/Kv7.3 channels. STXBP1 had no
      direct effects on M current but dampened the inhibition produced by Syn-1A by
      abrogating Syn-1A binding to Kv7 channels. The mutation p.W28*, but not p.P480L,
      failed to rescue M current from Syn-1A inhibition. Biochemical analysis showed
      that unlike the mutation p.W28*, the mutation p.P480L did not affect STXBP1
      expression and reduced the interaction of Syn-1A with Kv7 channels. SIGNIFICANCE:
      These data indicate that there is a functional link between STXBP1 and Kv7
      channels via Syn-1A, which may be important for regulating M-channel activity and
      neuronal excitability. They suggest also that a defect in Kv7 channel activity or
      regulation could be one of the consequences of some STXBP1 mutations associated
      with EOEEs. Furthermore, our data reveal that STXBP1 mutations associated with
      the Ohtahara syndrome do not necessarily result in protein haploinsufficiency.

PMID- 29067684
TI  - The role of nonbilayer phospholipids in mitochondrial structure and function.
AB  - Mitochondrial structure and function are influenced by the unique phospholipid
      composition of its membranes. While mitochondria contain all the major classes of
      phospholipids, recent studies have highlighted specific roles of the nonbilayer
      forming phospholipids phosphatidylethanolamine (PE) and cardiolipin (CL) in the
      assembly and activity of mitochondrial respiratory chain (MRC) complexes. The
      nonbilayer phospholipids are cone-shaped molecules that introduce curvature
      stress in the bilayer membrane and have been shown to impact mitochondrial fusion
      and fission. In addition to their overlapping roles in these mitochondrial
      processes, each nonbilayer phospholipid also plays a unique role in mitochondrial
      function; for example, CL is specifically required for MRC supercomplex
      formation. Recent discoveries of mitochondrial PE- and CL-trafficking proteins
      and prior knowledge of their biosynthetic pathways have provided targets for
      precisely manipulating nonbilayer phospholipid levels in the mitochondrial
      membranes in vivo. Thus, the genetic mutants of these pathways could be valuable
      tools in illuminating molecular functions and biophysical properties of
      nonbilayer phospholipids in driving mitochondrial bioenergetics and dynamics.

PMID- 29067687
TI  - Relationship Between Ideal Cardiovascular Health and Disability in Older Adults:
      The Chilean National Health Survey (2009-10).
AB  - This study aimed to examine the relationship between disability and the American
      Heart Association metric of ideal cardiovascular health (CVH) in older adults
      from the 2009-10 Chilean National Health Survey. Data from 460 older adults were
      analyzed. All subjects were interviewed using the standardized World Health
      Survey, which includes 16 health-related questions and assesses the domains of
      mobility, self-care, pain and discomfort, cognition, interpersonal activities,
      vision, sleep and energy, and affect. A person who responds with a difficulty
      rating of severe, extreme, or unable to do in at least one of these eight
      functioning domains is considered to have a disability. Ideal CVH was defined as
      meeting the ideal levels of four behaviors (smoking, body mass index, physical
      activity, diet adherence) and three factors (total cholesterol, fasting glucose,
      blood pressure). Logistic regression analysis suggested that ideal physical
      activity reduces the odds of disability (odds ratio (OR) = 0.55, 95% confidence
      interval (CI) = 0.36-0.85). Moreover, participants with intermediate (3-4
      metrics) (OR = 0.63, 95% CI = 0.41-0.97) and ideal (5-7 metrics) (OR = 0.51, 95%
      CI = 0.24-0.97) CVH profiles had lower odds of disability independent of history
      of vascular events and arthritis disease than those with a poor profile (0-2
      metrics). In conclusion, despite the cross-sectional design, this study suggests
      the importance of promoting ideal CVH because of their relationship with
      disability.

PMID- 29067688
TI  - The evidence for laser treatments to the vulvo-vagina: Making sure we do not
      repeat past mistakes.
AB  - Following menopause, up to 49% of women will experience genitourinary symptoms
      such as vaginal itching, dryness, dyspareunia and incontinence as a result of
      oestrogen deficiency. Treatments such as vaginal lubricants and moisturisers only
      temporarily relieve symptoms, while local oestrogen treatments are often
      unacceptable or unsafe for many women. Recently, a novel laser treatment has been
      proposed as a non-invasive, long-term solution to vulvo-vaginal and urinary
      symptoms. While preliminary histological results have been promising, its
      therapeutic, clinical effect has yet to be determined. However, despite the
      scarcity of evidence for its safety and long-term benefit, laser treatments are
      widely marketed for a range of genitourinary symptoms, with high uptake by both
      clinicians and women alike. This review aims to examine the evidence for laser
      treatments to the vulvo-vagina and to evaluate its safety and efficacy. Our
      results include 17 studies investigating the effect of laser therapy for vulvo
      vaginal symptoms, seven for its effects on urinary incontinence and four for
      histology. These are limited to non-randomised, observational data with small
      sample sizes between 15 to 175 women and follow-up duration from none to two
      years. As such, strong evidence for laser efficacy and safety is limited and
      warrants more robust, placebo-controlled, randomised trials before widespread
      implementation.

PMID- 29067686
TI  - Association between gamma marker, human leucocyte antigens and killer
      immunoglobulin-like receptors and the natural course of human cytomegalovirus
      infection: a pilot study performed in a Sicilian population.
AB  - Natural killer (NK) cells provide a major defence against human cytomegalovirus
      (HCMV) infection through the interaction of their surface receptors, including
      the activating and inhibitory killer immunoglobulin-like receptors (KIRs), and
      human leucocyte antigen (HLA) class I molecules. Also gamma marker (GM)
      allotypes, able to influence the NK antibody-dependent cell-mediated
      cytotoxicity, appear to be involved in the immunological control of virus
      infections, including HCMV. In some cases, their contribution requires epistatic
      interaction with other genes of the immune system, such as HLA. In the present
      report, with the aim of gaining insight into the immune mechanisms controlling
      HCMV, we have studied the possible associations among humoral and NK responses,
      and HCMV infections. In a previous study we assessed whether the KIR and HLA
      repertoire might influence the risk of developing symptomatic (n = 60) or
      asymptomatic (n = 60) disease after primary HCMV infection in the immunocompetent
      host. In the present study, the immunocompetent patients with primary symptomatic
      HCMV infection were genotyped for GM3/17 and GM23 allotypes, along with the 60
      participants with a previous asymptomatic infection as controls. Notwithstanding
      the presence of missing data record, advanced missing data recovery techniques
      were able to show that individuals carrying the GM23 allotypes, both homozygous
      and heterozygous, GM17/17, HLA-C2 and Bw4T KIR-ligand groups are associated with
      the risk of developing symptomatic infection. Our findings on the role of both
      cellular and humoral immunity in the control of HCMV infection should be of value
      in guiding efforts to reduce HCMV-associated health complications in the elderly,
      including immunosenescence, and in transplantation.

PMID- 29067689
TI  - Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX-type gene
      cluster.
AB  - Botulinum neurotoxins are highly toxic substances and are all encoded together
      with one of two alternative gene clusters, the HA or the OrfX gene cluster. Very
      little is known about the function and structure of the proteins encoded in the
      OrfX gene cluster, which in addition to the toxin contains five proteins (OrfX1,
      OrfX2, OrfX3, P47, and NTNH). We here present the structures of OrfX2 and P47,
      solved to 2.1 and 1.8 A, respectively. We show that they belong to the TULIP
      protein superfamily, which are often involved in lipid binding. OrfX1 and OrfX2
      were both found to bind phosphatidylinositol lipids.

PMID- 29067691
TI  - Spinal decision making for respiratory muscle recruitment?

PMID- 29067690
TI  - Phosphorylation of Aspergillus fumigatus PkaR impacts growth and cell wall
      integrity through novel mechanisms.
AB  - Protein kinase A (PKA) signaling is essential for growth and virulence of the
      fungal pathogen Aspergillus fumigatus. Little is known concerning the regulation
      of this pathway in filamentous fungi. Employing liquid chromatography-tandem mass
      spectroscopy, we identified novel phosphorylation sites on the regulatory subunit
      PkaR, distinct from those previously identified in mammals and yeasts, and
      demonstrated the importance of two phosphorylation clusters for hyphal growth and
      cell wall-stress response. We also identified key differences in the regulation
      of PKA subcellular localization in A. fumigatus compared with other species. This
      is the first analysis of the phosphoregulation of a PKA regulatory subunit in a
      filamentous fungus and uncovers critical mechanistic differences between PKA
      regulation in filamentous fungi compared with mammals and yeast species,
      suggesting divergent targeting opportunities.

PMID- 29067693
TI  - Newly raised anti-VAChT and anti-ChAT antibodies detect cholinergic cells in
      chicken embryos.
AB  - The autonomic nervous system consists of sympathetic and parasympathetic nerves,
      which functionally antagonize each other to control physiology and homeostasis of
      organs. However, it is largely unexplored how the autonomic nervous system is
      established during development. In particular, early formation of parasympathetic
      network remains elusive because of its complex anatomical structure. To
      distinguish between parasympathetic (cholinergic) and sympathetic (adrenergic)
      ganglia, vesicular acetylcholine transporter (VAChT) and choline O
      acetyltransferase (ChAT), proteins associated with acetylcholine synthesis, are
      known to be useful markers. Whereas commercially available antibodies against
      these proteins are widely used for mammalian specimens including mice and rats,
      these antibodies do not work satisfactorily in chickens, although chicken is an
      excellent model for the study of autonomic nervous system. Here, we newly raised
      antibodies against chicken VAChT and ChAT proteins. One monoclonal and three
      polyclonal antibodies for VAChT, and one polyclonal antibody for ChAT were
      obtained, which were available for Western blotting analyses and
      immunohistochemistry. Using these verified antibodies, we detected cholinergic
      cells in Remak ganglia of autonomic nervous system, which form in the dorsal
      aspect of the digestive tract of chicken E13 embryos. The antibodies obtained in
      this study are useful for visualization of cholinergic neurons including
      parasympathetic ganglia.

PMID- 29067692
TI  - Glucocorticoids promote a glioma stem cell-like phenotype and resistance to
      chemotherapy in human glioblastoma primary cells: Biological and prognostic
      significance.
AB  - Glioma stem cells (GSCs) are glioblastoma (GBM) cells that are resistant to
      therapy and can give rise to recurrent tumors. The identification of patient
      related factors that support GSCs is thus necessary to design effective therapies
      for GBM patients. Glucocorticoids (GCs) are used to treat GBM-associated edema.
      However, glucocorticoids participate in the physiological response to
      psychosocial stress, which has been linked to poor cancer prognosis. This raises
      concern that glucocorticoids affect the tumor and GSCs. Here, we treated primary
      human GBM cells with dexamethasone and evaluated GC-driven changes in cell
      morphology, proliferation, migration, gene expression, secretory activity and
      growth as neurospheres. Dexamethasone treatment of GBM cells appeared to promote
      the development of a GSC-like phenotype and conferred resistance to physiological
      stress and chemotherapy. We also analyzed a potential correlation between GC
      treatment and tumor recurrence after surgical excision in a population-based
      consecutive cohort of 48 GBM patients, adjusted for differences in known
      prognostic factors concerning baseline and treatment characteristics. In this
      cohort, we found a negative correlation between GC intake and progression-free
      survival, regardless of the MGMT methylation status. In conclusion, our findings
      raise concern that treatment of GBM with GCs may compromise the efficacy of
      chemotherapy and may support a GSC population, which could contribute to tumor
      recurrence and the poor prognosis of the disease.

PMID- 29067694
TI  - Administration of platelet concentrates suspended in bicarbonated Ringer's
      solution in children who had platelet transfusion reactions.
AB  - BACKGROUND AND OBJECTIVES: Adverse reactions to platelet transfusions are a
      problem. Children with primary haematological and malignant diseases may
      experience allergic transfusion reactions (ATRs) to platelet concentrates (PCs),
      which can be prevented by giving washed PCs. A new platelet additive solution,
      using bicarbonated Ringer's solution and acid-citrate-dextrose formula A (BRS-A),
      may be better for platelet washing and storage, but clinical data are scarce.
      MATERIALS AND METHODS: A retrospective cohort study for consecutive cases was
      performed between 2013 and 2017. For 24 months, we transfused washed PCs
      containing BRS-A to children with primary haematological and malignant diseases
      and previous adverse reactions. Patients transfused with conventional PCs
      (containing residual plasma) were assigned as controls, and results were compared
      in terms of frequency of ATRs, corrected count increment (CCI) and occurrence of
      bleeding. We also studied children transfused with PCs washed by a different
      system as historical controls. RESULTS: Thirty-two patients received 377
      conventional PC transfusions. ATRs occurred in 12 (37.5%) patients from
      transfused with 18 (4.8%) bags. Thirteen patients, who experienced reactions to
      regular PCs in plasma, then received 119 transfusion bags of washed PCs
      containing BRS-A, and none had ATRs to washed PCs containing BRS-A. Before study
      period, six patients transfused 137 classical washed PCs with different platelet
      additive solution, under same indication, ATRs occurred in one (16.7%) patient
      from transfused with one (0.7%) bags. CCIs (24 h) in were lower with classical
      washed PCs (1.26 +/- 0.54) compared to regular PCs in plasma (2.07 +/- 0.76) (P <
      0.001), but there was no difference between washed PCs containing BRS-A (2.14 +/-
      0.77) and regular PCs (2.21 +/- 0.79) (P = 0.769), and we saw no post-transfusion
      bleeding. CONCLUSION: Washed PCs containing BRS-A appear to prevent ATRs without
      loss of transfusion efficacy in children with primary haematological and
      malignant diseases. Their efficacy should be further evaluated through larger
      prospective clinical trials.

PMID- 29067695
TI  - Towards bedside washing of stored red blood cells: a prototype of a simple
      apparatus based on microscale sedimentation in normal gravity.
AB  - BACKGROUND AND OBJECTIVES: Infusion of by-products of red blood cell (RBC)
      storage-induced degradation as well as of the residual plasma proteins and the
      anticoagulant-preservative solution contained in units of stored blood serve no
      therapeutic purpose and may be harmful to some patients. Here, we describe a
      prototype of a gravity-driven system for bedside washing of stored RBCs.
      MATERIALS AND METHODS: Stored RBCs were diluted to 10% haematocrit (Hct) with
      normal saline, matching the conventional washing procedure. The dilute RBC
      suspensions were passed through a column of coiled tubing to allow RBC
      sedimentation in normal gravity, thus separating them from the washing solution.
      Washed RBCs were collected using bifurcations located along the tubing. Washing
      efficiency was quantified by measuring Hct, morphology, deformability, free
      haemoglobin and total-free protein. RESULTS: The gravity-driven washing system
      operating at 0.5 ml/min produced washed RBCs with final Hct of 36.7 +/- 3.4%
      (32.3-41.2%, n = 10) and waste Hct of 3.4 +/- 0.7% (2.4-4.3%, n = 10), while
      removing 80% of free haemoglobin and 90% of total-free protein. Washing improved
      the ability of stored RBCs to perfuse an artificial microvascular network by 20%.
      The efficiency of washing performed using the gravity-driven system was not
      significantly different than that of conventional centrifugation. CONCLUSIONS:
      This proof-of-concept study demonstrates the feasibility of washing stored RBCs
      using a simple, disposable system with efficiency comparable to that of
      conventional centrifugation, and thus represents a significant first step towards
      enabling low-cost washing of stored blood at bedside.

PMID- 29067697
TI  - A comparison of different ways of including baseline counts in negative binomial
      models for data from falls prevention trials.
AB  - A common design for a falls prevention trial is to assess falling at baseline,
      randomize participants into an intervention or control group, and ask them to
      record the number of falls they experience during a follow-up period of time.
      This paper addresses how best to include the baseline count in the analysis of
      the follow-up count of falls in negative binomial (NB) regression. We examine the
      performance of various approaches in simulated datasets where both counts are
      generated from a mixed Poisson distribution with shared random subject effect.
      Including the baseline count after log-transformation as a regressor in NB
      regression (NB-logged) or as an offset (NB-offset) resulted in greater power than
      including the untransformed baseline count (NB-unlogged). Cook and Wei's
      conditional negative binomial (CNB) model replicates the underlying process
      generating the data. In our motivating dataset, a statistically significant
      intervention effect resulted from the NB-logged, NB-offset, and CNB models, but
      not from NB-unlogged, and large, outlying baseline counts were overly influential
      in NB-unlogged but not in NB-logged. We conclude that there is little to lose by
      including the log-transformed baseline count in standard NB regression compared
      to CNB for moderate to larger sized datasets.

PMID- 29067696
TI  - Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase
      inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis.
AB  - This study determined the pharmacokinetics, antinociceptive, and anti
      inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB
      (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid)
      in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of
      seven adult healthy mares (n = 4-6/treatment) were administered 3 MUg LPS into
      one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1,
      0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks
      washout between. Two investigators independently assigned pain scores (at rest,
      walk and trot) and lameness scores before and up to 48 hr after t-TUCB/LPS.
      Responses to touching the joint skin to assess tactile allodynia, plasma, and
      synovial fluid (SF) t-TUCB concentrations were determined before and up to 48 hr
      after t-TUCB/LPS. Blood and SF were collected for clinical laboratory evaluations
      before and up to 48 hr after t-TUCB/LPS. Areas under the curves of pain and
      lameness scores were calculated and compared between control and treatments. Data
      were analyzed using repeated measures ANOVA with Dunnett or Bonferroni post-test.
      p < .05 was considered significant. Data are mean +/- SEM. Compared to control,
      pain, lameness, and tactile allodynia were significantly lower with 1 mg/kg t
      TUCB, but not the other doses. For 0.1, 0.3, and 1 mg/kg t-TUCB treatments,
      plasma terminal half-lives were 13 +/- 3, 13 +/- 0.5, and 24 +/- 5 hr, and
      clearances were 68 +/- 15, 48 +/- 5, and 14 +/- 1 ml hr-1  kg-1 . The 1 mg/kg t
      TUCB reached the SF at high concentrations. There were no important anti
      inflammatory effects. In conclusion, sEH inhibition with t-TUCB may provide
      analgesia in horses with inflammatory joint pain.

PMID- 29067698
TI  - Double trouble: Co-occurrence of testosterone deficiency and body fatness
      associated with all-cause mortality in US men.
AB  - BACKGROUND: Testosterone deficiency (TD, total testosterone <=350 ng/dL [12.15
      nmol L-1 ]) and obesity epidemic are growing in parallel in the United States.
      Yet, the sequelae of TD and obesity on the risk of mortality remain unclear.
      OBJECTIVE: To investigate whether the co-occurrence of TD and overall obesity
      (body mass index >=30 kg/m2 ), and abdominal obesity (waist circumference >=102
      cm), is associated with a risk of all-cause mortality in American men. DESIGN:
      The data were obtained from the NHANES 1999-2004 and the Linked Mortality File
      (December 31, 2011). A total of 948 participants aged >=20 years old with
      endogenous sex hormones and adiposity measurements data were included in this
      study. RESULTS: Over a median of 9.5 years of follow-up, 142 men died of any
      cause in this cohort. Multivariable analysis showed a 2.60 fold increased risk of
      death among men with TD compared with men without TD (Hazard Ratio [HR] = 2.60;
      95% confidence interval [CI] = 1.20-5.80). No evidence for interaction between TD
      and overall or abdominal obesity with risk of death (Pinteraction >= .80).
      However, only after comparing men with TD and abdominal obesity with men without
      TD and no abdominal obesity, we found a 3.30 fold increased risk of death (HR =
      3.30, 95% CI = 1.21-8.71). CONCLUSION: Men with co-occurrence of TD and abdominal
      obesity have a higher risk of mortality. The effect of co-occurrence of TD and
      abdominal obesity should be further explored with a larger and longer follow-up
      time study.

PMID- 29067699
TI  - Prediction errors for state occupation and transition probabilities in multi
      state models.
AB  - In this paper, we consider the estimation of prediction errors for state
      occupation probabilities and transition probabilities for multistate time-to
      event data. We study prediction errors based on the Brier score and on the
      Kullback-Leibler score and prove their properness. In the presence of right
      censored data, two classes of estimators, based on inverse probability weighting
      and pseudo-values, respectively, are proposed, and consistency properties of the
      proposed estimators are investigated. The second part of the paper is devoted to
      the estimation of dynamic prediction errors for state occupation probabilities
      for multistate models, conditional on being alive, and for transition
      probabilities. Cross-validated versions are proposed. Our methods are illustrated
      on the CSL1 randomized clinical trial comparing prednisone versus placebo for
      liver cirrhosis patients.

PMID- 29067700
TI  - Polyphenol oxidase from Pectobacterium atrosepticum: identification and cloning
      of gene and characteristics of the enzyme.
AB  - In the present study, we attempted to elucidate if the harmful phytopathogenic
      bacteria of Pectobacterium genus (P. atrosepticum) possess the enzymes for
      oxidation of phenolic compounds. Polyphenol oxidase (laccase) activity was
      revealed in P. atrosepticum cell lysates. Using bioinformatic analysis, an ORF
      encoding a putative copper-containing polyphenol oxidase of 241 amino acids with
      a predicted molecular mass of 25.9 kDa was found. This protein (named Pal1)
      shares significant level of identity with laccases of a new type described for
      several bacterial species. Cloning and expression of the pal1 gene and the
      analysis of corresponding recombinant protein confirmed that Pal1 possessed
      laccase activity. The recombinant Pal1 protein was characterized in terms of
      substrate specificity, kinetic parameters, pH and temperature optimum,
      sensitivity to inhibitors and metal content. Pal1 demonstrated alkali- and thermo
      tolerance. The kinetic parameters Km and kcat for 2,6-dimethoxyphenol were 0.353
      +/- 0.062 mM and 98.79 +/- 4.9 s-1 , respectively. The protein displayed high
      tolerance to sodium azide, sodium fluoride, NaCl, SDS and cinnamic acid. The
      transcript level of the pal1 gene in P. atrosepticum was shown to be induced by
      plant-derived phenolic compound (ferulic acid) and copper sulfate.

PMID- 29067701
TI  - Development of a Flexible-Monomer Two-Body Carbon Dioxide Potential and Its
      Application to Clusters up to (CO2 )13.
AB  - A flexible-monomer two-body potential energy function was developed that
      approaches the high level CCSD(T)/CBS potential energy surface (PES) of carbon
      dioxide (CO2 ) systems. This function was generated by fitting the electronic
      energies of unique CO2 monomers and dimers to permutationally invariant
      polynomials. More than 200,000 CO2 configurations were used to train the
      potential function. Comparisons of the PESs of six orientations of flexible CO2
      dimers were evaluated to demonstrate the accuracy of the potential. Furthermore,
      the potential function was used to determine the minimum energy structures of CO2
      clusters containing as many as 13 molecules. For isomers of (CO2 )3 , the
      potential demonstrated energetic agreement with the M06-2X functional and
      structural agreement of the B2PLYP-D functional at substantially reduced
      computational costs. A separate function, fit to MP2/aug-cc-pVDZ reference
      energies, was developed to directly compare the two-body potential to the ab
      initio MP2 level of theory. (c) 2017 Wiley Periodicals, Inc.

PMID- 29067702
TI  - Simulation-based evaluation of the linear-mixed model in the presence of an
      increasing proportion of singletons.
AB  - Data in medical sciences often have a hierarchical structure with lower level
      units (e.g. children) nested in higher level units (e.g. departments). Several
      specific but frequently studied settings, mainly in longitudinal and family
      research, involve a large number of units that tend to be quite small, with units
      containing only one element referred to as singletons. Regardless of sparseness,
      hierarchical data should be analyzed with appropriate methodology such as, for
      example linear-mixed models. Using a simulation study, based on the structure of
      a data example on Ceftriaxone consumption in hospitalized children, we assess the
      impact of an increasing proportion of singletons (0-95%), in data with a low,
      medium, or high intracluster correlation, on the stability of linear-mixed models
      parameter estimates, confidence interval coverage and F test performance. Some
      techniques that are frequently used in the presence of singletons include
      ignoring clustering, dropping the singletons from the analysis and grouping the
      singletons into an artificial unit. We show that both the fixed and random
      effects estimates and their standard errors are stable in the presence of an
      increasing proportion of singletons. We demonstrate that ignoring clustering and
      dropping singletons should be avoided as they come with biased standard error
      estimates. Grouping the singletons into an artificial unit might be considered,
      although the linear-mixed model performs better even when the proportion of
      singletons is high. We conclude that the linear-mixed model is stable in the
      presence of singletons when both lower- and higher level sample sizes are fixed.
      In this setting, the use of remedial measures, such as ignoring clustering and
      grouping or removing singletons, should be dissuaded.

PMID- 29067703
TI  - Red cell distribution width predicts death and appropriate therapy in patients
      with implantable cardioverter defibrillator: A simple measurement with prognostic
      value in a variety of diseases, may help in better selection of patients who will
      benefit the most from this device.
AB  - BACKGROUND: Red cell distribution width (RDW) is a measure of the size variation
      of erythrocytes. Its prognostic value has been described in a variety of cardiac
      and noncardiac diseases. Implantable cardioverter defibrillator (ICD) is useful
      in preventing sudden cardiac death in high-risk patients, but many of these
      patients continue to survive without needing ICD therapy. We sought to examine
      whether RDW, with its prognostic values, can benefit in risk stratification of
      patients with ICD by predicting death and ICD therapy, and thus help in the
      selection of patients who will benefit the most from ICD, and minimizing its
      implantation in others at low risk of death and arrhythmias. METHODS: In a
      retrospective study, we enrolled patients with ICD implanted for both primary and
      secondary prevention of sudden cardiac death. Baseline RDW values, demographics,
      and clinical characteristics, as well as the occurrence of death or first
      appropriate ICD therapy in postimplantation follow-up were collected. We examined
      whether RDW can predict higher-risk ICD-implanted patients prone to death and
      first appropriate ICD therapy (the combined outcome). RESULTS: Final population
      included 432 patients. Compared to others, patients in the upper RDW tertile were
      older and had more comorbidities and outcomes. In multivariate analysis including
      RDW, age, gender, and ejection fraction, RDW was the only predictor of the
      combined outcome. CONCLUSION: RDW may be useful in risk stratification of
      patients selected for ICD implantation. But larger prospective randomized trials
      are needed.

PMID- 29067704
TI  - Separation of chiral compounds using magnetic molecularly imprinted polymer
      nanoparticles as stationary phase by microchip capillary electrochromatography.
AB  - In this work, a simple and rapid approach was developed for separation and
      detection of chiral compounds based on a magnetic molecularly imprinted polymer
      modified poly(dimethylsiloxane) (PDMS) microchip coupled with electrochemical
      detection. Molecularly imprinted polymers were prepared employing Fe3 O4
      nanoparticles (NPs) as the supporting substrate and norepinephrine as the
      functional monomer in the presence of template molecule in a weak alkaline
      solution. After extracting the embedded template molecules, Fe3 O4
      @polynorepinephrine NPs (MIP-Fe3 O4 @PNE NPs) showed specific molecular
      recognition selectivity and high affinity towards the template molecule, which
      were then used as stationary phase of microchip capillary electrochromatography
      for chiral compounds separation. Mandelic acid and histidine enantiomers were
      used as model compounds to test the chiral stationary phase. By using R-mandelic
      acid as the template molecule, mandelic acid enantiomer was effectively separated
      and detected on the MIP-Fe3 O4 @PNE NPs modified PDMS microchip. Moreover, the
      successful separation of histidine enantiomers on the MIP-Fe3 O4 @PNE NPs
      modified microchip using L-histidine as template molecule was also achieved.

PMID- 29067706
TI  - Introduction-Festschrift in Honor of Prof. Volker Bubeta.

PMID- 29067707
TI  - Lenalidomide therapy in patients with myelodysplastic syndrome/myeloproliferative
      neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).

PMID- 29067705
TI  - Demographic and epidemiologic characterization of transfusion recipients from
      four US regions: evidence from the REDS-III recipient database.
AB  - BACKGROUND: Blood transfusion is one of the most common medical procedures during
      hospitalization in the United States. To understand the benefits of transfusion
      while mitigating potential risks, a multicenter database containing detailed
      information on transfusion incidence and recipient outcomes would facilitate
      research. STUDY DESIGN AND METHODS: The Recipient Epidemiology and Donor
      Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion
      recipient database utilizing data from hospital electronic health records at 12
      participating hospitals in four geographic regions. Inpatient and outpatient data
      on transfusion recipients from January 1, 2013 to December 31, 2014 included
      patient age, sex, ethnicity, primary diagnosis, type of blood product provided,
      issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and
      hospital outcomes. Transfusion incidence per encounter was calculated by blood
      product and various patient characteristics. RESULTS: During the 2-year study
      period, 80,362 (12.5%) inpatient encounters involved transfusion. Among
      inpatients, the most commonly transfused blood products were red blood cells
      (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%).
      Among patients who received transfusions, the median number of RBC units was one,
      the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4
      g/dL. Encounter mortality increased with patient age, the number of units
      transfused, and the use of platelet or plasma products. The most commonly
      reported transfusion reaction was febrile nonhemolytic. CONCLUSION: The database
      contains comprehensive data regarding transfusion use and patient outcomes. The
      current report describes an evaluation of the first 2 years of a planned, 4-year,
      linked blood donor-component-recipient database, which represents a critical new
      resource for transfusion medicine researchers.

PMID- 29067708
TI  - Preliminary study of the application of transthoracic echocardiography-guided
      three-dimensional printing for the assessment of structural heart disease.
AB  - OBJECTIVE: To investigate the feasibility and diagnostic value of a preoperative
      transthoracic echocardiography-guided three-dimensional printed model (TTE-guided
      3DPM) for the assessment of structural heart disease (SHD). METHODS: Fourty-four
      patients underwent cardiac surgery at Tianjin Chest Hospital. The patients were
      preoperatively assessed using TTE-guided 3DPM, which was compared to conventional
      three-dimensional transthoracic echocardiography (3DTTE) along with direct
      intraoperative findings, which were considered the "gold standard." Twelve
      patients had SHD, including four with mitral prolapse, two with partial
      endocardial cushion defects, two with secondary atrial septal defects, two with
      rheumatic mitral stenosis, one with tetralogy of Fallot, and one with a
      ventricular septal defect (VSD). Thirty-two patients who did not have SHDs were
      designated as the negative control group. RESULTS: The sensitivity and
      specificity of the TTE-guided 3DPM were greater than or equal to those of the
      3DTTE. The P-value of the McNemar test of 3DTTE was >.05, which indicates that
      the difference was not statistically significant (Kappa = 0.745, P < .001). The P
      value of the McNemar test of TTE-guided 3DPM was >.05, which indicates that the
      difference was not statistically significant (Kappa = 0.955, P < .001). A
      comparison of 3DTTE and TTE-guided 3DPM resulted in a P-value >.05, which
      indicates that the difference was not statistically significant (Kappa = 0.879, P
      < .001). TTE-guided 3DPM displayed the 3D structure of SHDs and cardiac lesions
      clearly and was consistent with the intra-operative findings. CONCLUSION:
      Transthoracic echocardiography-guided three-dimensional printed model (TTE-guided
      3DPM) provides essential information for preoperative evaluation and decision
      making for patients with SHDs.

PMID- 29067709
TI  - Sensitive skin in Korean population: An epidemiological approach.
AB  - BACKGROUND/PURPOSE: Sensitive skin is characterized by uncomfortable sensations
      in response to multiple factors that do not normally have irritant properties. We
      used an epidemiological approach to evaluate the prevalence and characteristics
      of sensitive skin in a Korean population, and compared the results with those of
      populations from other countries. METHODS: A representative nationwide sample of
      1000 Koreans aged >=15 years was selected. The methodology used in this study
      (questionnaires) was the same as that used in similar studies conducted in other
      countries. RESULTS: Sensitive skin was present in 56.8% of the Koreans. The
      prevalence of sensitive skin was highest among countries such as the USA (44.6%),
      Europe (38.4%), Russia (39.7%), Brazil (34.2%), and Japan (54.5%). Participants
      with sensitive skin were more likely to accompany skin disorders than those with
      non-sensitive skin (72.3% vs 38.0%; P < .001). Sensitive skin group were 2-3
      times more reactive to climatic and environmental factors, cosmetics, and food
      items than non-sensitive skin group. CONCLUSION: The prevalence of sensitive skin
      in Korea is the highest among countries in which such investigation has been
      conducted. The sensitive skin group appears more likely to experience
      dermatological reactions to unexpected factors than the non-sensitive skin group.

PMID- 29067710
TI  - Standardized ileal digestibility of amino acids in European soya bean and
      rapeseed products fed to growing pigs.
AB  - This study was conducted to determine the chemical composition and standardized
      ileal digestibility coefficients (SID) of crude protein (CP) and amino acids (AA)
      of European soya bean and rapeseed products in pigs. Six soya bean and two
      rapeseed products were used as the sole dietary source of CP and AA, including
      raw (FFSB) and roasted full-fat soya beans (FFSBRoasted ), soya bean (SBC) and
      rapeseed cake (RSC), and rapeseed meal (RSM) from Bavaria (Germany), soya bean
      meal (SBM) from the Danube region (Austria; SBMAustria ), a commercially
      available standard SBM (SBMStd ) and an imported genetically modified organism
      free SBM (SBMGMO-free ). Eight ileal- cannulated pigs with an initial body weight
      of 32 +/- 2 kg were allotted to a row-column design with eight diets and six
      periods of seven days each. Trypsin inhibitor activity (TIA) ranged from 1.8 in
      SBMStd to 24.5 mg/g DM in FFSB. The SID of CP and all AA in FFSBRoasted were
      greater than in FFSB, but lower when compared to SBC and SBMAustria (p < .05).
      The SID of CP and all AA (except glutamic acid) were not different between SBC
      and SBMAustria , but the SID of CP and all AA (except methionine) were greater (p
      < .05) in SBC than in SBMGMO-free . Furthermore, the SID of CP and most AA showed
      a quadratic response with decreasing TIA, and there exists a quadratic response
      in SID of CP and all AA with increasing lysine to CP ratio and neutral detergent
      insoluble nitrogen (p < .05). In conclusion, variation in chemical composition
      and SID of CP and AA was observed in different European soya bean and rapeseed
      products as influenced by differences in processing conditions. European SBC and
      SBMAustria can be used as alternative to imported SBMGMO-free and SBMStd in diets
      for growing pigs.

PMID- 29067711
TI  - Food allergy in EAACI journals (2016).
AB  - Over the last years we have observed considerable progress in the area of food
      allergy, particularly in children. This review article focusses on important
      contributions which have lately been published in the three journals of the
      European Academy of Allergy and Clinical Immunology. A better understanding of
      allergens as well as the mechanisms of sensitization and tolerance induction may
      hopefully lead to a more targeted management of food allergy in the near future.

PMID- 29067712
TI  - The Modern Profile of Tuberculosis: Developing the TB Social Survey to understand
      contemporary social patterns in tuberculosis.
AB  - Social disparities in tuberculosis have been documented for decades, yet to date
      there has not been a comprehensive study to examine the contemporary causes of
      these disparities. Local public health departments, and particularly public
      health nursing staff are charged with delivering directly observed therapy to
      individuals with tuberculosis disease. As a result of the frequency and duration
      of treatment, practitioners delivering therapy are often well-acquainted with the
      lives and challenges of their constituents. Thus, through these practitioners
      there exists a deep repository of knowledge on the drivers of social disparities
      in tuberculosis disease. Partnering with local public health departments, we
      developed a survey instrument aimed at understanding the social profile of
      individuals with tuberculosis disease in metropolitan Detroit, Michigan. We
      discuss the development and implementation of the survey instrument as well as
      challenges in developing partnerships between academic researchers and local
      public health practitioners. This study can serve as a framework for both
      academic researchers and public health practitioners interested in addressing
      social disparities in infectious disease.

PMID- 29067713
TI  - Feature analysis of ultrasound elastography image for quantitative assessment of
      cutaneous carcinoma.
AB  - BACKGROUND: To evaluate the feasibility of using quantitative texture features
      computed from high frequency ultrasound and ultrasound elastography (USE) images
      in the discrimination of benign from malignant skin lesions. METHODS: A
      commercial ultrasound system with a 14 MHz transducer was used to visualize skin
      lesions requiring biopsy on clinical evaluation. Patients were enrolled over a 6
      month period and imaged prospectively by operators blind to the histopathologic
      diagnosis. Anatomic ultrasound and USE imaging of the skin lesions was performed
      using a 2-4 mm gel standoff pad before biopsy and histopathologic evaluation. The
      ElastoAnalysis software developed for the texture analysis of USE images was
      provided by Hitachi. The software computes thirteen texture features within a
      region of interest (ROI), which have demonstrated promise in diagnostic
      characterization of liver fibrosis staging and in quantitative elastography of
      breast cancer. This approach has not yet been studied in the quantitative
      assessment of skin cancer. Results were retrospectively compared to the
      histopathologic diagnosis and a diagnostic criteria with the goal of maximizing
      sensitivity was evaluated for each textural feature. RESULTS: Of the 37 lesions
      included, among 30 patients who participated, 12 lesions were malignant and 25
      were benign. Eleven out of thirteen textural metrics computed by the software
      were useful in differentiating benign from malignant lesions with 100%
      sensitivity and specificities ranging from 28% to 85%. CONCLUSIONS: This
      feasibility study demonstrated that feature analysis of USE may be useful in
      quantitatively differentiating cancerous from benign primary solitary skin
      lesions prior to biopsy.

PMID- 29067715
TI  - Comments on "Sesamol ameliorates radiation induced DNA damage in hematopoietic
      system of whole body gamma-irradiated mice".

PMID- 29067714
TI  - Low anti-pig antibody levels are key to the success of solid organ
      xenotransplantation: But is this sufficient?

PMID- 29067716
TI  - In ovo feeding of carbohydrates for broilers-a systematic review.
AB  - The purpose of this systematic review was to evaluate the evidence that the
      injection of carbohydrate-based solutions into embryonated eggs improves broiler
      performance. A literature search was conducted in April 2017 using the keywords
      broiler, carbohydrate, in ovo, nutrition and poultry. Only papers that involved
      in ovo carbohydrate injections in poultry were used in this study. After specific
      selection criteria, 17 papers were selected. The quality scoring system of the
      selected studies was based on the injection methodology, use of control groups,
      type of solution injected, period of injection, egg and hens characteristics,
      number of variables analysed and the statistical design. Among papers, there was
      no standardised procedure in to inoculate the solutions. Nevertheless, in
      general, in ovo feeding of carbohydrates decreases the hatch rate, improves the
      hatch weight, but it does not seem to influence the post-hatch performance of
      broilers. The inoculation of 75 mg of glucose in the albumen seems to bring
      better results. Further studies are needed to improve the technical methodology
      of in ovo injections for commercial use.

PMID- 29067717
TI  - Haptic augmented skin surface generation toward telepalpation from a mobile skin
      image.
AB  - BACKGROUND/PURPOSE: Very little is known about the methods of integrating
      palpation techniques to existing mobile teleskin imaging that delivers low
      quality tactile information (roughness) for telepalpation. However, no study has
      been reported yet regarding telehaptic palpation using mobile phone images for
      teledermatology or teleconsultations of skincare. METHODS: This study is
      therefore aimed at introducing a new algorithm accurately reconstructing a haptic
      augmented skin surface for telehaptic palpation using a low-cost clip-on
      microscope simply attached to a mobile phone. Multiple algorithms such as
      gradient-based image enhancement, roughness-adaptive tactile mask generation,
      roughness-enhanced 3D tactile map building, and visual and haptic rendering with
      a three-degrees-of-freedom (DOF) haptic device were developed and integrated as
      one system. RESULTS: Evaluation experiments have been conducted to test the
      performance of 3D roughness reconstruction with/without the tactile mask. The
      results confirm that reconstructed haptic roughness with the tactile mask is
      superior to the reconstructed haptic roughness without the tactile mask.
      Additional experiments demonstrate that the proposed algorithm is robust against
      varying lighting conditions and blurring. In last, a user study has been designed
      to see the effect of the haptic modality to the existing visual only interface
      and the results attest that the haptic skin palpation can significantly improve
      the skin exam performance. CONCLUSION: Mobile image-based telehaptic palpation
      technology was proposed, and an initial version was developed. The developed
      technology was tested with several skin images and the experimental results
      showed the superiority of the proposed scheme in terms of the performance of
      haptic augmentation of real skin images.

PMID- 29067718
TI  - Estimating the extinction date of the thylacine with mixed certainty data.
AB  - The thylacine (Thylacinus cynocephalus), one of Australia's most characteristic
      megafauna, was the largest marsupial carnivore until hunting, and potentially
      disease, drove it to extinction in 1936. Although thylacines were restricted to
      Tasmania for 2 millennia prior to their extinction, recent so-called plausible
      sightings on the Cape York Peninsula in northern Queensland have emerged, leading
      some to speculate the species may have persisted undetected. We compiled a data
      set that included physical evidence, expert-validated sightings, and unconfirmed
      sightings up to the present day and implemented a range of extinction models
      (focusing on a Bayesian approach that incorporates all 3 types of data by
      modeling valid and invalid sightings as independent processes) to evaluate the
      likelihood of the thylacine's persistence. Although the last captive individual
      died in September 1936, our results suggested that the most likely extinction
      date would be 1940. Our other extinction models estimated the thylacine's
      extinction date between 1936 and 1943, and the most optimistic scenario indicated
      that the species did not persist beyond 1956. The search for the thylacine, much
      like similar efforts to rediscover other recently extinct charismatic taxa, is
      likely to be fruitless, especially given that persistence on Tasmania would have
      been no guarantee the species could reappear in regions that had been unoccupied
      for millennia. The search for the thylacine may become a rallying point for
      conservation and wildlife biology and could indirectly help fund and support
      critical research in understudied areas such as Cape York. However, our results
      suggest that attempts to rediscover the thylacine will be unsuccessful and that
      the continued survival of the thylacine is entirely implausible based on most
      current mathematical theories of extinction.

PMID- 29067719
TI  - Radiological prevalence of equine odontoclastic tooth resorption and
      hypercementosis.
AB  - BACKGROUND: Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is
      a painful and progressive dental disease that mainly affects the incisors and
      canine teeth of aged horses. Diagnosis is based on radiographs to detect early
      stages of the disease. EOTRH is probably underdiagnosed and its prevalence in
      Germany unknown. OBJECTIVE: This study was performed to determine the
      radiological prevalence of EOTRH in a large horse population in Berlin
      Brandenburg, Germany. STUDY DESIGN: Prevalence study. METHODS: The study
      population (142 horses) consisted of all horses 10 years and older that were
      presented at the Equine Hospital for a routine dental examination. The horses
      were either presented as clinical cases (CC population) or belonged to a riding
      school (RS population). Digital radiographs of the incisor dentition were taken
      and evaluated for changes related to EOTRH, leading to an overall classification
      for each horse. RESULTS: The mean age of the study population was 21 years and
      ranged from 10 to 37 years. Overall, 94% of all horses had at least minor and 62%
      had moderate to severe radiological changes of the incisor teeth associated to
      EOTRH. No horse older than 14 years was without radiological signs of EOTRH and
      all horses over 28 years of age had at least moderate radiological changes of the
      incisor teeth. MAIN LIMITATIONS: The clinical cases group might have a bias
      towards horses with existing dental problems such as EOTRH, because they were
      presented explicitly for dental care to a clinic. CONCLUSION: Focusing on
      radiological changes, this study shows that EOTRH is a common condition of horses
      in Berlin-Brandenburg. With older age, disease is more frequent and radiological
      changes become more severe. Since no horse older than 14 years was without
      radiological findings, it is likely that mild changes may be associated with the
      normal tooth ageing process.

PMID- 29067720
TI  - Magnetic Susceptibility Study of Sub-Pico-emu Sample Using a Micromagnetometer:
      An Investigation through Bistable Spin-Crossover Materials.
AB  - A promising and original method to study the spin-transition in bistable spin
      crossover (SCO) materials using a magnetoresistive multiring sensor and its self
      generated magnetic field is reported. Qualitative and quantitative studies are
      carried out combining theoretical and experimental approaches. The results show
      that only a small part of matter dropped on the sensor surface is probed by the
      device. At a low bias-current range, the number of detected nanoparticles depends
      on the amplitude of the current. However, in agreement with the theoretical
      model, the stray voltage from the particles is proportional to the current
      squared. By changing both the bias current and the concentration of particle
      droplet, the thermal hysteresis of an ultrasmall volume, 1 * 10-4 mm3 , of SCO
      particles is measured. The local probe of the experimental setup allows a highest
      resolution of 4 * 10-14 emu to be reached, which is never achieved by
      experimental methods at room temperature.

PMID- 29067721
TI  - The perivascular microenvironment in Epstein-Barr virus positive primary central
      nervous system lymphoma: The role of programmed cell death 1 and programmed cell
      death ligand 1.
AB  - It has been shown that high expression of certain immune checkpoint molecules,
      including those of the programmed death protein 1/programmed death ligand 1 (PD
      1/PD-L1) axis, can be utilized to regulate immunosuppression in the
      microenvironment of malignant neoplasms. For the purpose of clarifying the immune
      escape mechanism of primary central nervous system lymphomas (PCNSLs),
      particularly in Epstein-Barr virus (EBV)-positive cases, markers for PD-1, PD-L1,
      tumor-associated macrophages (TAMs), and tumor-infiltrating lymphocytes (TILs) in
      39 surgical specimens of PCNSLs (17 EBV-positive, 22 EBV-negative) were
      investigated by immunohistochemistry. Staining for PD-L1 was scored as follows: (
      ), no staining; (1+), 0-30% positive cells; (2+), 30-60% positive cells; and
      (3+), >60% positive cells. In EBV-positive cases, PD-L1 was detected in both
      lymphoma cells and TAMs in 12/17 cases, and in TAMs only in 4/17 cases. The mean
      number of PD-1, TIA-1 (a marker for cytotoxic T-cells), and FOXP3 (a marker for
      regulatory T-cells)-positive TILs in EBV-positive cases was 36.4 +/- 45.9, 390 +/
      603, and 9.88 +/- 15.1, respectively. In EBV-negative cases, PD-L1 was detected
      in both lymphoma cells and TAMs in 11/22 cases, and in TAMs only in 4/22 cases.
      The mean of PD-1, TIA-1 and FOXP3-positive lymphocytes in EBV-negative cases was
      67.3 +/- 82.0, 158 +/- 206 and 9.32 +/- 17.5, respectively. We found no
      significant difference in the number of FOXP3-positive, lymphocytes between EBV
      positive and negative cases. However, there were significantly higher numbers of
      PD-1-positive lymphocytes in the former, and significantly higher numbers of TIA
      1-positive lymphocytes in the latter (P < 0.05). The combined data indicate that
      expression of PD-L1 by lymphoma cells and TAMs mediate the trafficking of TILs,
      which may explain the immune-escape process of PCNSLs. In addition, EBV infection
      appears to affect the trafficking mechanism of TILs, and may thus play an
      important role in the microenvironment immunity of these tumors.

PMID- 29067722
TI  - Ventricular dyssynchrony as a marker of latent carditis in children with acute
      rheumatic fever: A tissue Doppler imaging.
AB  - OBJECTIVE: We aimed to investigate the hypothesis that the presence of left
      ventricular (LV) dyssynchrony in children with acute rheumatic fever (ARF)
      children may be a predictor of latent rheumatic carditis. METHODS: Eighty-nine
      children with ARF and 45 healthy control children were included the study. LV
      dyssynchrony was investigated by color-coded tissue Doppler imaging. RESULTS: LV
      dyssynchrony parameters including Ts-SD-12, Ts-12, Ts-SD-6, and Ts-6 were found
      to be prolonged in children with ARF than in controls (P < .001). We found that
      45.2% in children with ARF without carditis had LV dyssynchrony (Ts-SD-12 >= 34.4
      ms), while 63.4% in children with ARF with carditis had LV dyssynchrony. Follow
      up analysis demonstrated that children with arthritis and without dyssynchrony
      had no adverse events (recurrent rheumatic activity, development of valvular
      diseases; heart failure and atrial fibrillation), while those with LV
      dyssynchrony had events rate of 40.9% (P < .001). Likewise, children with
      carditis had event rates of 63.4%. Ts-SD-12 was found to be correlated with hs
      CRP (r = .63; P < .001). Receiver-operating characteristic (ROC) curve analysis
      showed that a Ts-SD-12 >= 36.5 was the optimal cutoff value in predicting
      unfavorable outcome in patients with ARF, with a sensitivity of 95% and
      specificity of 82%. CONCLUSIONS: We found that children with ARF without any
      evidence of carditis had a significant LV systolic dyssynchrony spite of normal
      EF. LV dyssynchrony in those children had a significant event rates on follow-up.
      These results highlighted the incremental value of LV dyssynchrony as a marker of
      subclinical carditis in children with ARF.

PMID- 29067723
TI  - Efficacy of VDT PACE-like regimens in treatment of relapsed/refractory multiple
      myeloma.
AB  - Experience with intensive chemotherapy for relapsed/refractory multiple myeloma
      (RRMM) using VDT PACE regimen and its modifications (VDT PACE-like regimens:
      VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141
      patients with RRMM who received VPLRs at our center between 2006 and 2017 in an
      intent-to-treat analysis. Median age was 59.7 years and 66.7% of patients were
      male. A median of 2.2 years (range 0.02-11.4) separated diagnosis of myeloma and
      inititation of VPLR. High-risk cytogenetics were present in 52.4% patients.
      Patients received a median of 4 (range 1-14) prior therapies, including stem cell
      transplant (SCT) in 66.7% patients. Ninety-five (67.4%) patients received VDT
      PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other
      VPLRs. Patients received a median of 1 cycle (range 1-9) of VPLR. We observed >=
      minimal response in 68.4%, >= partial response (PR) in 54.4% and >= very good PR
      in 10.3% patients. Median progression-free survival was 3.1 months (95% CI, 1.9
      3.9) and median overall survival (OS) was 8.1 months (CI, 6.2-9.9). One-hundred
      and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%)
      received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for
      those who received SCT after VPLR was 15.1 months (CI, 10.3-20.8). Age >= 60
      years (hazard ratio [HR] 2.3 [CI, 1.4-3.7]; P = 0.0008) and R-ISS III stage (HR-
      2.4 [CI, 1.3-4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR.
      VPLRs are effective in heavily pre-treated RRMM. In fit patients, SCT can be used
      to consolidate the response to VPLR.

PMID- 29067724
TI  - Diabetes training for community health workers on an American Indian reservation.
AB  - OBJECTIVES: To improve the knowledge and skills of community health workers
      (CHWs) on an American Indian (AI) Reservation related to the management of
      diabetes to allow CHWs, with no prior formal diabetes education to work more
      effectively with individuals in the community with diabetes. Training was
      provided in six "face-to-face" sessions with the CHWs using the Centers for
      Disease Control and Prevention CHW Training Resource on Heart Disease and Stroke.
      DESIGN AND SAMPLE: This is a quality improvement program guided by the Model for
      Improvement: Plan, Do, Study, Act and using a pre-post evaluation design. Ten AI
      CHWs were recruited for the training. MEASURES: Knowledge and attitudes,
      participation rates, and participant satisfaction were measured. RESULTS:
      Knowledge increased overall with largest changes in diabetes, depression and
      cholesterol. Diabetes attitudes were high and consistent with those found in
      caregivers who support patient-centered care. Participants reported learning,
      liking the class, and finding the materials helpful. CONCLUSION: This QI program
      provided by a public health nurse improved CHW's knowledge of diabetes and the
      management of diabetes. Next steps include formalizing the Reservation's CHW
      training program, expanding this training to other AI Health Service areas, and
      measuring the impact of CHWs in the community.

PMID- 29067725
TI  - Pediatric to adult care co-location transitional model for youth with sickle cell
      disease.

PMID- 29067726
TI  - Falls in Parkinson's disease: A complex and evolving picture.
AB  - Falls are a major determinant of poor quality of life, immobilization, and
      reduced life expectancy in people affected by Parkinson's disease (PD) and in
      older adults more generally. Although many questions remain, recent research has
      advanced the understanding of this complex problem. The goal of this review is to
      condense new knowledge of falls in PD from prodromal to advanced disease, taking
      into account risk factors, assessment, and classification as well as treatment.
      The fundamental steps of clinical and research-based approaches to falls are
      described, namely, the identification of fall risk factors, clinical and
      instrumental methods to evaluate and classify fall risk, and the latest evidence
      to reduce or delay falls in PD. We summarize recent developments, the direction
      in which the field should be heading, and what can be recommended at this stage.
      We also provide a practical algorithm for clinicians.(c) 2017 International
      Parkinson and Movement Disorder Society.

PMID- 29067727
TI  - Editorial Comment to Diagnosis and treatment of patients with prostatic abscess
      in the post-antibiotic era.

PMID- 29067728
TI  - Pharmacokinetics of enrofloxacin and ciprofloxacin in Atlantic horseshoe crabs
      (Limulus polyphemus) after single injection.
AB  - The pharmacokinetics of enrofloxacin and the metabolite ciprofloxacin were
      studied in horseshoe crabs after a single injection of 5 mg/kg. Twelve Atlantic
      horseshoe crabs (Limulus polyphemus) of undetermined age were injected with
      enrofloxacin into the dorsal cardiac sinus. Hemolymph samples were collected by
      syringe and needle at regular intervals for 120 hr. Samples were analyzed by high
      pressure liquid chromatography and compartmental analysis performed on the
      results. Following injection, the elimination half-life (T1/2), peak
      concentration, area under the curve (AUC), and volume of distribution (VD) for
      enrofloxacin were 27.9 (29.13) hr, 8.98 (18.09) MUg/ml, 367.38 (35.41) hr MUg/ml,
      and 0.575 (20.48) L/kg, respectively (mean value, CV%). For ciprofloxacin, the
      elimination T1/2, peak concentration, and AUC were 61.36 (34.55) hr, 2.34 (24.11)
      MUg/ml, and 304.46 (24.69) MUg hr/ml. In these animals, the ciprofloxacin
      concentrations comprised an average of 45.8% of the total fluoroquinolone
      concentrations, which is substantial compared to other marine invertebrates. The
      total AUC produced (sum of enrofloxacin and ciprofloxacin) was 682.69 +/- 180.61
      MUg hr/ml. Concentrations that were achieved after a single dose of 5 mg/kg
      horseshoe crabs were sufficient to treat bacteria susceptible to enrofloxacin and
      ciprofloxacin.

PMID- 29067729
TI  - Antioxidant status of serum bilirubin, uric acid and albumin in pemphigus
      vulgaris.
AB  - BACKGROUND: Oxidative stress and low antioxidant status are implicated in the
      pathogenesis of inflammatory and autoimmune diseases. Pemphigus vulgaris (PV) is
      an extremely severe autoimmune bullous dermatosis characterized by
      intraepithelial bullae on the skin and mucosa, and its antioxidant status is not
      fully understood. AIM: To assess correlations between PV and serum antioxidant
      levels of bilirubin, uric acid (UA) and albumin. METHODS: We enrolled 116
      patients newly diagnosed with PV who were admitted to the First Affiliated
      Hospital of Guangxi Medical University (Guangxi, China), and 108 healthy controls
      (HCs). Clinical characteristics and laboratory parameters of patients were
      retrospectively analysed. RESULTS: Our survey shows that compared with the HC
      groups, serum levels of bilirubin [total bilirubin (Tbil), direct bilirubin
      (Dbil) and indirect bilirubin (Ibil)], UA and albumin were significantly lower in
      patients with PV, regardless of sex. In all groups, serum Tbil, Dbil, Ibil, UA
      and albumin levels were lower for women than for men. Severity of pemphigus was
      slightly negatively associated with Tbil, Dbil and Ibil, but was not associated
      with UA or albumin. Moreover, when the data were adjusted for the covariances of
      age and sex separately, Tbil, Dbil, Ibil, UA and albumin were all relevant to PV.
      CONCLUSIONS: Our findings demonstrate that serum levels of bilirubin (Tbil, Dbil
      and Ibil), UA and albumin are reduced in patients with PV supporting the
      hypothesis that oxidative stress and antioxidant status are important in the
      pathogenic mechanism of PV.

PMID- 29067731
TI  - A random-censoring Poisson model for underreported data.
AB  - A major challenge when monitoring risks in socially deprived areas of under
      developed countries is that economic, epidemiological, and social data are
      typically underreported. Thus, statistical models that do not take the data
      quality into account will produce biased estimates. To deal with this problem,
      counts in suspected regions are usually approached as censored information. The
      censored Poisson model can be considered, but all censored regions must be
      precisely known a priori, which is not a reasonable assumption in most practical
      situations. We introduce the random-censoring Poisson model (RCPM) which accounts
      for the uncertainty about both the count and the data reporting processes.
      Consequently, for each region, we will be able to estimate the relative risk for
      the event of interest as well as the censoring probability. To facilitate the
      posterior sampling process, we propose a Markov chain Monte Carlo scheme based on
      the data augmentation technique. We run a simulation study comparing the proposed
      RCPM with 2 competitive models. Different scenarios are considered. RCPM and
      censored Poisson model are applied to account for potential underreporting of
      early neonatal mortality counts in regions of Minas Gerais State, Brazil, where
      data quality is known to be poor.

PMID- 29067730
TI  - Simultaneous QSM and metabolic imaging of the brain using SPICE.
AB  - PURPOSE: To map brain metabolites and tissue magnetic susceptibility
      simultaneously using a single three-dimensional 1 H-MRSI acquisition without
      water suppression. METHODS: The proposed technique builds on a subspace imaging
      method called spectroscopic imaging by exploiting spatiospectral correlation
      (SPICE), which enables ultrashort echo time (TE)/short pulse repetition time (TR)
      acquisitions for 1 H-MRSI without water suppression. This data acquisition scheme
      simultaneously captures both the spectral information of brain metabolites and
      the phase information of the water signals that is directly related to tissue
      magnetic susceptibility variations. In extending this scheme for simultaneous QSM
      and metabolic imaging, we increase k-space coverage by using dual density sparse
      sampling and ramp sampling to achieve spatial resolution often required by QSM,
      while maintaining a reasonable signal-to-noise ratio (SNR) for the spatiospectral
      data used for metabolite mapping. In data processing, we obtain high-quality QSM
      from the unsuppressed water signals by taking advantage of the larger number of
      echoes acquired and any available anatomical priors; metabolite spatiospectral
      distributions are reconstructed using a union-of-subspaces model. RESULTS: In
      vivo experimental results demonstrate that the proposed method can produce
      susceptibility maps at a resolution higher than 1.8 * 1.8 * 2.4 mm3 along with
      metabolite spatiospectral distributions at a nominal spatial resolution of 2.4 *
      2.4 * 2.4 mm3 from a single 7-min MRSI scan. The estimated susceptibility values
      are consistent with those obtained using the conventional QSM method with 3D
      multi-echo gradient echo acquisitions. CONCLUSION: This article reports a new
      capability for simultaneous susceptibility mapping and metabolic imaging of the
      brain from a single 1 H-MRSI scan, which has potential for a wide range of
      applications. Magn Reson Med 79:13-21, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 29067732
TI  - A Novel Construction of Lentiviral Vectors for Eliminating Tumorigenic Cells from
      Pluripotent Stem Cells.
AB  - The risk of tumor formation poses a challenge for human pluripotent stem cell
      (hPSC)-based transplantation therapy. Specific and total elimination of
      tumorigenic hPSCs by suicide genes (SGs) has not been achieved because no
      methodology currently exists for testing multiple candidate transgene constructs.
      Here, we present a novel method for efficient generation of tumorigenic cell
      targeting lentiviral vectors (TC-LVs) with diverse promoters upstream of a
      fluorescent protein and SGs. Our two-plasmid system achieved rapid and
      simultaneous construction of different TC-LVs with different promoters.
      Ganciclovir (GCV) exerted remarkable cytotoxicity in herpes simplex virus
      thymidine kinase-transduced hPSCs, and high specificity for undifferentiated
      cells was achieved using the survivin promoter (TC-LV.Surv). Moreover, GCV
      treatment completely abolished teratoma formation by TC-LV.Surv-infected hPSCs
      transplanted into mice, without harmful effects. Thus, TC-LV can efficiently
      identify the best promoter and SG for specific and complete elimination of
      tumorigenic hPSCs, facilitating the development of safe regenerative medicine.
      Stem Cells 2018;36:230-239.

PMID- 29067733
TI  - Whole exome and whole genome sequencing with dried blood spot DNA without whole
      genome amplification.
AB  - Newborn screening (NBS) for rare conditions is performed in all 50 states in the
      USA. We have partnered with the California Department of Public Health Genetic
      Disease Laboratory to determine whether sufficient DNA can be extracted from
      archived dried blood spots (DBS) for next-generation sequencing in the hopes that
      next-generation sequencing can play a role in NBS. We optimized the DNA
      extraction and sequencing library preparation protocols for residual infant DBS
      archived over 20 years ago and successfully obtained acceptable whole exome and
      whole genome sequencing data. This sequencing study using DBS DNA without whole
      genome amplification prior to sequencing library preparation provides evidence
      that properly stored residual newborn DBS are a satisfactory source of DNA for
      genetic studies.

PMID- 29067734
TI  - Light Robots: Bridging the Gap between Microrobotics and Photomechanics in Soft
      Materials.
AB  - For decades, roboticists have focused their efforts on rigid systems that enable
      programmable, automated action, and sophisticated control with maximal movement
      precision and speed. Meanwhile, material scientists have sought compounds and
      fabrication strategies to devise polymeric actuators that are small, soft,
      adaptive, and stimuli-responsive. Merging these two fields has given birth to a
      new class of devices-soft microrobots that, by combining concepts from
      microrobotics and stimuli-responsive materials research, provide several
      advantages in a miniature form: external, remotely controllable power supply,
      adaptive motion, and human-friendly interaction, with device design and action
      often inspired by biological systems. Herein, recent progress in soft
      microrobotics is highlighted based on light-responsive liquid-crystal elastomers
      and polymer networks, focusing on photomobile devices such as walkers, swimmers,
      and mechanical oscillators, which may ultimately lead to flying microrobots.
      Finally, self-regulated actuation is proposed as a new pathway toward fully
      autonomous, intelligent light robots of the future.

PMID- 29067735
TI  - An {As4 Cu4 [Cu(H2 O)]12 } Cluster Incorporated within Four [Nb7 O22 ]9- Units.
AB  - A gigantic 16-copper-containing 28-niobate cluster, Na14 K7 H5 {As4 Cu4 [Cu(H2
      O)]12 Nb28 O109 }?37.5 H2 O (1), has been prepared by a one-pot reaction, which
      is the first example of arsenic copper clusters containing polyoxoniobate, and
      the first tetrahedral arrangement of both the Cu cluster and the [Nb7 O22 ]9-
      subunits.

PMID- 29067737
TI  - Biomechanical Assessment of Restored Mandibular Molar by Endocrown in Comparison
      to a Glass Fiber Post-Retained Conventional Crown: 3D Finite Element Analysis.
AB  - PURPOSE: To compare equivalent and contact stresses in a mandibular molar
      restored by all-ceramic crowns through two methods: ceramic endocrowns and
      ceramic crowns supported by fiber-reinforced composite (FRC) posts and core, by
      using 3D finite element analysis during normal masticatory load. MATERIALS AND
      METHODS: Three 3D models of a mandibular first molar were made and labeled as
      such: intact molar with no restoration (A); ceramic endocrown-restored molar (B);
      ceramic crown supported by FRC posts and core restored molar (C). By using 3D FE
      analysis with contact components, normal masticatory load was simulated. The mvM
      stresses in all models were calculated. Maximal mvM stresses in the ceramic of
      restorations, dentin, and luting cement were contrasted among models and to
      values of materials' strength. Contact shear and tensile stresses in the
      restoration/tooth interface around restorations were also calculated. RESULTS:
      The highest mvM stress levels in the enamel and dentin for the tooth restored by
      ceramic endocrown were lower in the crown ceramic than in tooth restored with FRC
      posts and all-ceramic crowns; however, in the resin adhesive cement interface it
      was lower for ceramic crown supported by FRC posts than the in ceramic endocrown
      restoration. The maximum contact shear and tensile stress values along the
      restoration/tooth interface of ceramic endocrowns were lower than those with
      ceramic crowns supported by FRC posts. CONCLUSIONS: Ceramic endocrown
      restorations presented a lower mvM stress level in dentin than the conventional
      ceramic crowns supported by FRC posts and core. Ceramic endocrown restorations in
      molars are less susceptible to damage than those with conventional ceramic crowns
      retained by FRC posts. Ceramic endocrowns properly cemented in molars must not be
      fractured or loosen during normal masticatory load. Therefore, ceramic endocrowns
      are advised as practicable, minimally invasive, and esthetic restorations for
      root canal treated mandibular molars.

PMID- 29067736
TI  - RCSB Protein Data Bank: Sustaining a living digital data resource that enables
      breakthroughs in scientific research and biomedical education.
AB  - The Protein Data Bank (PDB) is one of two archival resources for experimental
      data central to biomedical research and education worldwide (the other key
      Primary Data Archive in biology being the International Nucleotide Sequence
      Database Collaboration). The PDB currently houses >134,000 atomic level
      biomolecular structures determined by crystallography, NMR spectroscopy, and 3D
      electron microscopy. It was established in 1971 as the first open-access, digital
      data resource in biology, and is managed by the Worldwide Protein Data Bank
      partnership (wwPDB; wwpdb.org). US PDB operations are conducted by the RCSB
      Protein Data Bank (RCSB PDB; RCSB.org; Rutgers University and UC San Diego) and
      funded by NSF, NIH, and DoE. The RCSB PDB serves as the global Archive Keeper for
      the wwPDB. During calendar 2016, >591 million structure data files were
      downloaded from the PDB by Data Consumers working in every sovereign nation
      recognized by the United Nations. During this same period, the RCSB PDB processed
      >5300 new atomic level biomolecular structures plus experimental data and
      metadata coming into the archive from Data Depositors working in the Americas and
      Oceania. In addition, RCSB PDB served >1 million RCSB.org users worldwide with
      PDB data integrated with ~40 external data resources providing rich structural
      views of fundamental biology, biomedicine, and energy sciences, and >600,000
      PDB101.rcsb.org educational website users around the globe. RCSB PDB resources
      are described in detail together with metrics documenting the impact of access to
      PDB data on basic and applied research, clinical medicine, education, and the
      economy.

PMID- 29067738
TI  - Giant Polarization Sustainability in Ultrathin Ferroelectric Films Stabilized by
      Charge Transfer.
AB  - Ferroelectricity is generally deteriorated or even vanishes when the
      ferroelectric films are downsized to unit cell scale. To maintain and enhance the
      polarization in nanoscale ferroelectrics are of scientific and technological
      importance. Here, giant polarization sustainability is reported in a series of
      ultrathin PbTiO3 films scaled down to three unit cells grown on NdGaO3 (110)
      substrates with La0.7 Sr0.3 MnO3 as bottom electrodes. Atomic mappings via
      aberration-corrected scanning transmission electron microscopy demonstrate the
      robust ferroelectricity for the sub-10 nm thick film. For the 1.2 nm thick film,
      the polarization reaches ~50 uC cm-2 . The 2 nm thick film possesses a
      polarization as high as the bulk value. The films ranging from 10 to 35 nm
      display a giant elongation of out-of-plane lattice parameter, which corresponds
      to a polarization of 100 uC cm-2 , 20% larger than that of the bulk PbTiO3 . The
      giant enhancement of polarization in the present films is proposed to result from
      the charge transfer at the La0.7 Sr0.3 MnO3 /PbTiO3 interface, as supported by
      the anomalous decrease of Mn valence measured from X-ray photoelectron
      spectroscopy. These results reveal the significant role of charge transfer at
      interfaces in improving large polarizations in ultrathin ferroelectrics and are
      meaningful for the development of future electronic devices.

PMID- 29067739
TI  - Transparent review at the European Journal of Neuroscience: experiences one year
      on.

PMID- 29067740
TI  - The Pericytic Phenotype of Adipose Tissue-Derived Stromal Cells Is Promoted by
      NOTCH2.
AB  - Long-term diabetes leads to macrovascular and microvascular complication. In
      diabetic retinopathy (DR), persistent hyperglycemia causes permanent loss of
      retinal pericytes and aberrant proliferation of microvascular endothelial cells
      (ECs). Adipose tissue-derived stromal cells (ASCs) may serve to functionally
      replace retinal pericytes and normalize retinal microvasculature during disease
      progression. We hypothesized that Notch signaling in ASC underlies regulation and
      stabilization of dysfunctional retinal microvascular networks such as in DR. ASC
      prominently and constitutively expressed NOTCH2. Genetic knockdown of NOTCH2 in
      ASC (SH-NOTCH2) disturbed the formation of vascular networks of human umbilical
      cord vein endothelial cells both on monolayers of ASC and in organotypical three
      dimensional cocultures with ASC. On ASC SH-NOTCH2, cell surface platelet-derived
      growth factor receptor beta was downregulated which disrupted their migration
      toward the chemoattractant platelet-derived growth factor beta subunits (PDGF-BB)
      as well as to conditioned media from EC and bovine retinal EC. This
      chemoattractant is secreted by pro-angiogenic EC in newly formed microvascular
      networks to attract pericytes. Intravitreal injected ASC SH-NOTCH2 in oxygen
      induced retinopathy mouse eyes did not engraft in the preexisting retinal
      microvasculature. However, the in vivo pro-angiogenic capacity of ASC SH-NOTCH2
      did not differ from controls. In this respect, multifocal electroretinography
      displayed similar b-wave amplitudes in the avascular zones when either wild type
      ASC or SH-NOTCH2 ASC were injected. In conclusion, our results indicate that
      NOTCH2 is essential to support in vitro vasculogenesis via juxtacrine
      interactions. In contrast, ongoing in vivo angiogenesis is influenced by
      paracrine signaling of ASC, irrespective of Notch signaling. Stem Cells
      2018;36:240-251.

PMID- 29067742
TI  - Non-invasive evaluation of Secukinumab efficacy in severe plaque psoriasis with
      confocal microscopy and optical coherence tomography: A case report.

PMID- 29067741
TI  - Synthetic liver function is detectable in transgenic porcine livers perfused with
      human blood.
AB  - In addition to immune barriers, molecular incompatibilities between species are
      predicted to limit pig liver survival in primate xenotransplantation models.
      Assessment and measurement of synthetic function of genetically modified porcine
      livers after ex vivo perfusion with human blood have not previously been
      described. Eight porcine livers from alpha1,3-galactosyl transferase knockout and
      human membrane cofactor (GalTKO.hCD46), six livers from GalTKO.hCD46 and N
      glycolylneuraminic acid knockout (GalTKO.hCD46.Neu5GcKO), and six livers from
      GalTKO.hCD46 with humanized decay-accelerating factor (hCD55), endothelial
      protein C receptor (hEPCR), tissue factor pathway inhibitor (hTFPI), and integrin
      associated protein (hCD47) (GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47) pigs were
      perfused with human blood under physiologic conditions. Timed blood samples were
      tested for liver enzymes and for pig-specific albumin production via Western
      blot. Porcine albumin levels increased with time in all experiments. By
      densitometry, GalTKO.hCD46.Neu5GcKO livers had the highest albumin levels,
      measured both as total produced, and when controlled for perfusion duration,
      compared to GalTKO.hCD46 (P = .068) and GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47
      livers (P = .04). Porcine livers perfused with human blood demonstrated the
      synthetic ability to produce albumin in all cases. GalTKO.hCD46.Neu5GcKO pig
      livers demonstrated the most robust albumin production. This suggests that the
      Neu5GcKO phenotype provides a protective effect on the graft due to decreased
      human antibody recognition and graft injury.

PMID- 29067743
TI  - Atomically Thin Femtojoule Memristive Device.
AB  - The morphology and dimension of the conductive filament formed in a memristive
      device are strongly influenced by the thickness of its switching medium layer.
      Aggressive scaling of this active layer thickness is critical toward reducing the
      operating current, voltage, and energy consumption in filamentary-type
      memristors. Previously, the thickness of this filament layer has been limited to
      above a few nanometers due to processing constraints, making it challenging to
      further suppress the on-state current and the switching voltage. Here, the
      formation of conductive filaments in a material medium with sub-nanometer
      thickness formed through the oxidation of atomically thin two-dimensional boron
      nitride is studied. The resulting memristive device exhibits sub-nanometer
      filamentary switching with sub-pA operation current and femtojoule per bit energy
      consumption. Furthermore, by confining the filament to the atomic scale, current
      switching characteristics are observed that are distinct from that in thicker
      medium due to the profoundly different atomic kinetics. The filament morphology
      in such an aggressively scaled memristive device is also theoretically explored.
      These ultralow energy devices are promising for realizing femtojoule and sub
      femtojoule electronic computation, which can be attractive for applications in a
      wide range of electronics systems that desire ultralow power operation.

PMID- 29067744
TI  - Scopoletin-standardized Morinda elliptica leaf extract suppressed inflammation
      and cartilage degradation to alleviate osteoarthritis: A preclinical study.
AB  - The effect of scopoletin-standardized Morinda elliptica leaf extract against
      osteoarthritis was investigated in ex vivo explant culture and preclinical rodent
      model. Thirty male rats were grouped (n = 6) into untreated osteoarthritis (OA),
      OA + Diclofenac (5 mg/kg), and OA + extract (200 and 400 mg/kg) and compared with
      healthy control. Monosodium iodoacetate were injected into the right intra
      articular knee joints to induce OA. The rats were evaluated for OA severity via
      physical (micro-CT and histological observations), biochemical, ELISA, and mRNA
      expression analysis (for inflammation and cartilage degradation biomarkers),
      after 28 days of treatment. The extract suppressed glycosaminoglycan release from
      the cartilage explant in the presence of Interleukin-1beta. The 200 mg/kg dose
      appeared better than 400 mg/kg dose, at reducing cartilage and subchondral bone
      erosions in OA-induced rats, by significantly down-regulating the collagenases
      and aggrecanase. The extract dose-dependently reduced serum inflammation
      biomarkers and increased bone formation biomarkers to near normal levels in the
      OA-induced rats. M. elliptica leaf scopoletin-standardised extract alleviated OA
      progression and articular cartilage structure, by ameliorating cartilage
      degradation, nitric oxide levels, inflammation, bone /cartilage homeostasis,
      collagenase/aggrecanase activities, chondrocytes survival, subchondral bone
      structure and integrity.

PMID- 29067745
TI  - Human umbilical cord blood relaxation times and susceptibility at 3 T.
AB  - PURPOSE: To characterize the magnetic susceptibility and relaxation times (T1 and
      T2 ) of fetal blood at 3 T as a function of the hematocrit (Hct) and oxygen
      saturation (sO2 ). METHODS: Susceptibility and relaxometry measurements were
      performed on cord blood specimens (N = 90, derived from six caesarean deliveries)
      with a range of hematocrits and oxygen saturations (0.09 < Hct < 0.82, 7 < sO2  <
      100%). To obtain simple, analytic relationships between MRI properties and blood
      properties, data were fit to established two-compartment (plasma and
      erythrocytes) models. RESULTS: Two-compartment models effectively described the
      cord blood data. The root-mean-squared deviation between the model and the data
      was 6.3, 10.3, and 1.3% for fits to T1 , T2 , and susceptibility measurements.
      Relaxometry data and estimated T1 and T2 model parameters were generally
      consistent with those reported in cord blood at 1.5 T and comparable to published
      values for adult blood. Notably, the measured value of Deltachideo , the
      susceptibility difference between fully oxygenated (sO2  = 100%) and deoxygenated
      (sO2  = 0) cord blood was approximately 20% lower than the established adult
      blood value (Deltachideo,cord  = 2.64 ppm, Deltachideo,adult  = 3.4 ppm).
      CONCLUSIONS: The described models and associated parameter values can be used to
      inform acquisition parameters, and interpret fetal/neonatal blood susceptibility
      measurements and relaxometry data acquired at 3 T with respect to hematocrit and
      sO2 . Magn Reson Med 79:3194-3206, 2018. (c) 2017 International Society for
      Magnetic Resonance in Medicine.

PMID- 29067746
TI  - Alternative Technique of Iris Orientation in a Custom-Made Ocular Prosthesis.
AB  - Accurate positioning of the iris is critical for the success of an ocular
      prosthesis. Precise duplication of size and location of the iris is essential for
      the establishment of realism, symmetry, and a natural-appearing gaze. This
      article explores an alternative procedure for positioning the iris in a custom
      made ocular prosthesis using a pupillary distance ruler (PD ruler). The
      orientation and mediolateral dimension of the iris of the natural eye was
      measured from the graduated scale on a PD ruler and transferred on to the
      sculpted scleral wax pattern. The iris button was positioned in the marked area,
      and the established orientation was evaluated for symmetry and a natural
      appearing gaze. Accurate, predictable, and easy positioning of the iris with the
      transfer of these dimensions to the definitive prosthesis provided a good result
      in terms of patient esthetics and satisfaction.

PMID- 29067747
TI  - Effects of carbon monoxide on early dysfunction and microangiopathy following
      GalT-KO porcine pulmonary xenotransplantation in cynomolgus monkeys.
AB  - BACKGROUND: Despite progress in the current genetic manipulation of donor pigs,
      most non-human primates were lost within a day of receiving porcine lung
      transplants. We previously reported that carbon monoxide (CO) treatment improved
      pulmonary function in an allogeneic lung transplant (LTx) model using miniature
      swine. In this study, we evaluated whether the perioperative treatment with low
      dose inhalation of CO has beneficial effects on porcine lung xenografts in
      cynomolgus monkeys (cynos). METHODS: Eight cynos received orthotopic left LTx
      using either alpha-1,3-galactosyltransferase knockout (GalT-KO; n = 2) or GalT-KO
      with human decay accelerating factor (hDAF) (GalT-KO/hDAF; n = 6) swine donors.
      These eight animals were divided into three groups. In Group 1 (n = 2), neither
      donor nor recipients received CO therapy. In Group 2 (n = 4), donors were treated
      with inhaled CO for 180-minute. In Group 3 (n = 2), both donors and recipients
      were treated with CO (donor: 180-minute; recipient: 360-minute). Concentration of
      inhaled CO was adjusted based on measured levels of carboxyhemoglobin in the
      blood (15%-20%). RESULTS: Two recipients survived for 3 days; 75 hours (no-CO)
      and 80 hours (CO in both the donor and the recipient), respectively. Histology
      showed less inflammatory cell infiltrates, intravascular thrombi, and hemorrhage
      in the 80-hour survivor with the CO treatment than the 75-hours non-CO treatment.
      Anti-non-Gal cytotoxicity levels did not affect the early loss of the grafts.
      Although CO treatment did not prolong overall xeno lung graft survival, the
      recipient/donor CO treatment helped to maintain platelet counts and inhibit TNF
      alpha and IL-6 secretion at 2 hours after revascularization of grafts. In
      addition, lung xenografts that were received recipient/donor CO therapy
      demonstrated fewer macrophage and neutrophil infiltrates. Infiltrating
      macrophages as well as alveolar epithelial cells in the CO-treated graft
      expressed heme oxygenase-1. CONCLUSION: Although further investigation is
      required, CO treatment may provide a beneficial strategy for pulmonary
      xenografts.

PMID- 29067748
TI  - The determination of nitrite by a graphene quantum dot fluorescence quenching
      method without sample pretreatment.
AB  - A method for quantitative analysis of nitrite was achieved based on fluorescence
      quenching of graphene quantum dots. To obtain reliable results, the effects of
      pH, temperature and reaction time on this fluorescence quenching system were
      studied. Under optimized conditions, decrease in fluorescence intensity of
      graphene quantum dots (F0 /F) showed a good linear relationship with nitrite
      concentration between 0.007692-0.38406 mmol/L and 0.03623-0.13043 MUmol/L; the
      limits of detection were 9.8 MUmol/L and 5.4 nmol/L, respectively. Variable
      temperature experiments, UV absorption spectra and thermodynamic calculations
      were used to determine the quenching mechanism, and indicated that it was an
      exothermic, spontaneous dynamic quenching process. This method was used to
      analyse urine samples, and showed that it could be applied to analyse biological
      samples.

PMID- 29067749
TI  - Combined Brain and Peripheral Nerve Stimulation in Chronic Stroke Patients With
      Moderate to Severe Motor Impairment.
AB  - OBJECTIVES: To evaluate effects of somatosensory stimulation in the form of
      repetitive peripheral nerve sensory stimulation (RPSS) in combination with
      transcranial direct current stimulation (tDCS), tDCS alone, RPSS alone, or sham
      RPSS + tDCS as add-on interventions to training of wrist extension with
      functional electrical stimulation (FES), in chronic stroke patients with moderate
      to severe upper limb impairments in a crossover design. We hypothesized that the
      combination of RPSS and tDCS would enhance the effects of FES on active range of
      movement (ROM) of the paretic wrist to a greater extent than RPSS alone, tDCS
      alone or sham RPSS + tDCS. MATERIALS AND METHODS: The primary outcome was the
      active ROM of extension of the paretic wrist. Secondary outcomes were ROM of
      wrist flexion, grasp, and pinch strength of the paretic and nonparetic upper
      limbs, and ROM of wrist extension of the nonparetic wrist. Outcomes were blindly
      evaluated before and after each intervention. Analysis of variance with repeated
      measures with factors "session" and "time" was performed. RESULTS: After
      screening 2499 subjects, 22 were included. Data from 20 subjects were analyzed.
      There were significant effects of "time" for grasp force of the paretic limb and
      for ROM of wrist extension of the nonparetic limb, but no effects of "session" or
      interaction "session x time." There were no significant effects of "session,"
      "time," or interaction "session x time" regarding other outcomes. CONCLUSIONS:
      Single sessions of PSS + tDCS, tDCS alone, or RPSS alone did not improve training
      effects in chronic stroke patients with moderate to severe impairment.

PMID- 29067750
TI  - Quality of life after living donor liver transplant for biliary atresia in Japan.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is an important outcome in
      solid organ transplantation. This study evaluated and explored the factors of
      generic and transplant-specific HRQOL in Japanese pediatric and adolescent
      patients with biliary atresia (BA) after living donor liver transplant (LDLT).
      METHODS: A cross-sectional survey using anonymous questionnaires was completed
      between April and July 2015. Patient medical records were accessed. The Japanese
      version of Pediatric Quality of Life InventoryTM Generic Core Scales and
      Transplant Modules (child self-report and parent proxy-report) was administered.
      RESULTS: Participants consisted of 75 patients (mean age at survey, 9.6 years)
      and 74 parents. Japanese patients reported higher generic and transplant-specific
      HRQOL (total score) than that reported by US patients with BA after LT (US I; age
      at survey, 7.2 years) and by US patients after solid organ transplant (US II; age
      at survey, 11.3 years; LT, 53.8%; effect size, 0.55-0.96). Japanese parents,
      however, rated their children's generic HRQOL (total score) similar to that rated
      by the US I and II parents (0.13 and 0.30, respectively) and reported lower
      transplant-specific HRQOL (total score) than that reported by US II (0.26).
      Although the number of types of prescribed drugs was a common factor in HRQOL,
      most demographic and medical factors (e.g. child's age at survey and consultation
      frequency) varied with reporter (i.e. patients and parents). CONCLUSIONS: The
      levels and factors of generic and transplant-specific HRQOL of Japanese pediatric
      and adolescent patients with BA after LDLT varied with reporter (i.e. patients or
      parents).

PMID- 29067751
TI  - Monitoring of fusion gene transcripts to predict relapse in pediatric acute
      myeloid leukemia.
AB  - BACKGROUND: In acute myeloid leukemia (AML), accurate detection of minimal
      residual disease (MRD) enables better risk-stratified therapy. There are few
      studies, however, on the monitoring of multiple fusion transcripts and evaluation
      of their accuracy as indicators of MRD at multiple time points. METHODS: We
      retrospectively examined RNA obtained from 82 pediatric AML patients enrolled in
      the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 study. The
      expression of six important fusion transcripts (AML1(RUNX1)-ETO, CBFB-MYH11,
      MLL(KMT2A)-AF9, MLL-ELL, MLL-AF6, and FUS-ERG) was analyzed at five time points
      30-40 days apart following diagnosis. RESULTS: In patients with AML1-ETO (n = 36
      at time point 5), all six patients with >3,000 copies and four of 30 patients
      with <=3,000 copies relapsed. AML1-ETO transcripts persisted during treatment
      even in patients without relapse, as well as CBFB-MYH11 transcripts. In contrast,
      in patients with MLL-AF9 (n = 9 at time point 5), two patients were positive for
      MLL-AF9 expression (>50 copies) and both relapsed. Only one of seven MLL-AF9
      negative patients relapsed. In the AML1-ETO group, MRD-positive patients (>3,000
      copies at time point 5) had significantly lower relapse-free survival (RFS; P <
      0.0001) and overall survival (OS; P = 0.009) than MRD-negative patients.
      Similarly, in the MLL-AF9 group, MRD-positive patients (>50 copies at time point
      5) had significantly lower RFS (P = 0.002) and OS (P = 0.002) than MRD-negative
      patients. CONCLUSIONS: Detection of MLL-AF9 transcripts on real-time quantitative
      polymerase chain reaction is a promising marker of relapse in pediatric AML. In
      contrast, the clinical utility of detecting AML1-ETO and CBFB-MYH11 expression is
      limited, although higher AML1-ETO expression can be a potential predictor of
      relapse when assessed according to an optimal threshold.

PMID- 29067753
TI  - The Impact of Self-Reported Impulsivity on the Course of Weight Is Mediated by
      Disinhibited Eating.
AB  - This study investigates the impact of impulsivity and the mediating role of
      disinhibited eating behaviour (DEB) on weight and weight trajectories in a large
      data set including obese non-treatment seeking individuals (obese control, n =
      138) and obese individuals who were either receiving a conventional treatment
      program (n = 227) or bariatric surgery (n = 123). Data was assessed one, 4 and 9
      years after baseline including self-reports for impulsivity and DEB. Results
      suggest a significant association between impulsivity and body mass index, which
      is partially mediated by DEB. Longitudinally, the influence of impulsivity on the
      course of weight after 9 years was fully mediated by DEB in obese control but not
      in the treatment groups. The results indicate an interplay between impulsivity
      and DEB with respect to obesity. Further research is needed to clarify how the
      mediation works and when it exerts its effect, in order to identify those that
      might profit from a specific (impulsivity-reducing) training. Copyright (c) 2017
      John Wiley & Sons, Ltd and Eating Disorders Association.

PMID- 29067752
TI  - Recent attempted and actual weight change in relation to pregnancy loss: a
      prospective cohort study.
AB  - OBJECTIVE: To assess weight change and attempted weight loss during the 12-18
      months before spontaneous conception in relation to the risk of pregnancy loss.
      DESIGN: Prospective cohort study. SETTING: United States, 2007-2011. METHODS:
      Women (n = 629) who were attempting pregnancy reported at baseline any weight
      loss attempts over the past 12 months, and their minimum and maximum weights
      during that time. Follow up lasted one to six menstrual cycles and throughout
      pregnancy. Using bodyweight measured at 4 weeks' gestation, participants were
      categorised as having weight loss >=5%, weight gain >=5%, both, or neither, over
      the previous 12-18 months. Log-binomial models adjusted for potential
      confounders. MAIN OUTCOME MEASURES: Risk ratio (RR) and 95% confidence interval
      (CI) of pregnancy loss. RESULTS: Attempted weight loss was reported by 44% of
      women and actual weight loss by 11%, but neither was consistently associated with
      pregnancy loss. The RR for recent weight gain >=5% was 1.65 (CI 1.09, 2.49).
      CONCLUSIONS: Weight gain over the period spanning 12-18 months pre-conception to
      4 weeks' gestation may increase the risk of pregnancy loss among fertile women
      with prior pregnancy losses. Attempted and actual weight loss were not associated
      with pregnancy loss; however, replication is needed from larger studies with data
      on particular weight-loss methods. TWEETABLE ABSTRACT: Recent weight gain before
      and around the time of conception may increase the risk of pregnancy loss.

PMID- 29067754
TI  - Influence of ejection fraction on cause-specific mortality in heart failure with
      preserved ejection fraction.

PMID- 29067755
TI  - Implementing routine outcome monitoring in public mental health services in
      Israel: Shared and unique challenges.
AB  - OBJECTIVES: This study aimed to assess the feasibility, benefits, and challenges
      of routine outcome monitoring (ROM) in a public mental health centre in Israel.
      This is the first initiation of ROM implementation in a setting of a large
      psychiatric hospital, affiliated with the largest health maintenance organization
      in Israel, Clalit Health Services. METHODS: Four ambulatory units were invited to
      participate in the implementation of ROM. Prior to initiation of recruitment,
      staff meetings were held and broad descriptions of current knowledge regarding
      benefits and challenges were discussed. Upon initiation of recruitment, patients
      completed outcome and process questionnaires during each session, and reports of
      patients' progress were sent to therapists soon after sessions ended. RESULTS:
      One hundred sixty-three patients were invited to participate in measurement and
      feedback of therapy outcomes. Overall, 101 patients and 32 therapists agreed and
      actively participated in the implementation phase of ROM, producing 535 evaluated
      measurements and reports. Clinical, methodological, legal, administrative, and
      ethical aspects of the implementation were encountered and documented throughout
      the implementation process. CONCLUSIONS: Medical confidentiality issues, as well
      as the multidisciplinary nature of hospital staff work, serve as central and
      unique challenges for incorporating ROM in a public psychiatric hospital. Other
      challenges that were previously reported in other implementation studies were
      also encountered and included therapist overload and objections, attrition, and
      the need for organizational support. Recommendations for future pioneering
      efforts for ROM implementation in large psychiatric facilities are discussed.

PMID- 29067756
TI  - Olmesartan-based monotherapy vs combination therapy in hypertension: A meta
      analysis based on age and chronic kidney disease status.
AB  - Antihypertensive monotherapy is often insufficient to control blood pressure
      (BP). Several recent guidelines advocate for initial combination drug therapy in
      many patients. This meta-analysis of seven randomized, double-blind studies (N =
      5888) evaluated 8 weeks of olmesartan medoxomil (OM)-based single-pill dual
      combination therapy (OM+amlodipine/azelnidipine or hydrochlorothiazide) vs OM
      monotherapy in adults with hypertension. BP-lowering efficacy, goal achievement,
      and adverse events were assessed in the full cohort and subgroups
      (elderly/nonelderly and patients with and without chronic kidney disease). In the
      full cohort at week 8, for dual therapy vs monotherapy, seated BP was lower
      (137.5/86.1 mm Hg vs 144.4/89.9 mm Hg), and the mean change from baseline in BP
      and BP goal achievement (<140/90 mm Hg) were greater (-22.7/-15.0 mm Hg vs -16.0/
      11.3 mm Hg and 51.2% vs 34.7%, respectively). Adverse events were similar between
      groups. BP-lowering efficacy among subgroups mirrored the findings in the full
      cohort whereby changes were significantly greater following OM dual-combination
      therapy vs OM monotherapy.

PMID- 29067757
TI  - Survivin Is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell
      Function.
AB  - Although mesenchymal stromal cells (MSCs) have significant potential in cell
      based therapies, little is known about the factors that regulate their functions.
      While exploring regulatory molecules potentially involved in MSC activities, we
      found that the endogenous multifunctional factor Survivin is essential for MSC
      survival, expansion, lineage commitment, and migration. Pharmacological or
      genetic blockade of Survivin expression in mouse and human bone marrow MSC
      enhances caspase 3 and 7 expression and reduces proliferation resulting in fewer
      MSC and clonogenic colony-forming unit-fibroblasts (CFU-F), whereas ectopic
      Survivin overexpression in MSC results in their expansion. Survivin is also
      required for the MSC proliferative responses to basic fibroblast growth factor
      and platelet derived growth factor. In a wound healing model, Survivin inhibition
      results in suppression of MSC migration to the wound site. In addition, loss of
      Survivin in MSCs compromises their hematopoiesis-supporting capacity. These
      results demonstrate that Survivin is a key regulator of mouse and human MSC
      function, and suggest that targeted modulation of Survivin in MSCs may have
      clinical utility to enhance MSC recovery and activity following insult or stress.
      Stem Cells 2018;36:123-129.

PMID- 29067758
TI  - Scoring model to predict massive post-partum bleeding in pregnancies with
      placenta previa: A retrospective cohort study.
AB  - AIM: We aimed to identify factors associated with massive post-partum bleeding in
      pregnancies with placenta previa and to establish a scoring model to predict post
      partum severe bleeding. METHODS: A retrospective cohort study was performed in
      506 healthy singleton pregnancies with placenta previa from 2006 to 2016. Cases
      with intraoperative blood loss (>=2000 mL), packed red blood cells transfusion
      (>=4), uterine artery embolization, or hysterectomy were defined as massive
      bleeding. After performing multivariable analysis, using the adjusted odds ratios
      (aOR), we formulated a scoring model. RESULTS: Seventy-three women experienced
      massive post-partum bleeding (14.4%). After multivariable analysis, seven
      variables were associated with massive bleeding: maternal old age (>=35 years;
      aOR 1.79, 95% confidence interval [CI] 1.00-3.20, P = 0.049), antepartum bleeding
      (aOR 4.76, 95%CI 2.01-11.02, P < 0.001), non-cephalic presentation (aOR 3.41,
      95%CI 1.40-8.30, P = 0.007), complete placenta previa (aOR 1.93, 95%CI 1.05-3.54,
      P = 0.034), anterior placenta (aOR 2.74, 95%CI 1.54-4.89, P = 0.001), multiple
      lacunae (>=4; aOR 2.77, 95%CI 1.54-4.99, P = 0.001), and uteroplacental
      hypervascularity (aOR 4.51, 95%CI 2.30-8.83, P < 0.001). We formulated a scoring
      model including maternal old age (<35: 0, >=35: 1), antepartum bleeding (no: 0,
      yes: 2), fetal non-cephalic presentation (no: 0, yes: 2), placenta previa type
      (incomplete: 0, complete: 1), placenta location (posterior: 0, anterior: 1),
      uteroplacental hypervascularity (no: 0, yes: 2), and multiple lacunae (no: 0,
      yes: 1) to predict post-partum massive bleeding. According to our scoring model,
      a score of 5/10 had a sensitivity of 81% and a specificity of 77% for predicting
      massive post-partum bleeding. The area under the receiver-operator curve was
      0.856 (P < 0.001). The negative predictive value was 95.9%. CONCLUSION: Our
      scoring model might provide useful information for prediction of massive post
      partum bleeding in pregnancies with placenta previa.

PMID- 29067759
TI  - Who benefits from fixed-dose combinations? Two-year statin adherence trajectories
      in initiators of combined amlodipine/atorvastatin therapy.
AB  - PURPOSE: We compared statin adherence in individuals initiating combined
      amlodipine/atorvastatin therapy as a fixed-dose (FDC) or free combination and
      identified subgroups benefiting most from FDCs. METHODS: We used a 10% sample of
      Australian Pharmaceutical Benefits Scheme dispensing data (2005-2015) to identify
      individuals initiating amlodipine and atorvastatin as an FDC (n = 3996) or free
      combination (n = 5434), with or without prior statin dispensing. We measured the
      proportion of days covered in each 30-day period over 24 months and classified
      patterns of statin adherence using group-based trajectory models. We identified
      predictors of adherence trajectories using logistic regression. RESULTS: The
      median age was 71 years, and 53% were female. We identified 4 patterns of statin
      adherence: near-perfect adherence (n = 5383), good adherence (n = 1893),
      declining adherence (n = 1247), and early nonadherence (n = 907). Compared with
      the free combination, FDC initiators were more likely to have near-perfect
      adherence if they were previously statin adherent irrespective of amlodipine dose
      (amlodipine 5 mg: OR = 1.61, 95% CI 1.38-1.87; amlodipine 10 mg: OR = 2.39, 95%
      CI 1.63-3.51) or they were previously statin nonadherent and initiated on the 5
      mg amlodipine dose (OR = 1.87, 95% CI 1.50-2.32). Statin-naive individuals
      initiating on the FDC with 10 mg amlodipine were less likely to have near-perfect
      adherence (OR = 0.60, 95% CI 0.41-0.88) and more likely to have early
      nonadherence (OR = 1.73, 95% CI 1.17-2.55). CONCLUSIONS: The
      amlodipine/atorvastatin FDC was associated with greater statin adherence among
      prevalent statin users, and individuals who initiated on lower amlodipine doses.
      The FDCs did not improve adherence in statin-naive individuals and in some cases
      resulted in poorer adherence.

PMID- 29067760
TI  - Hot debate in hot springs: Report on the second international meeting on SMC
      proteins.
AB  - The second international meeting on "SMC proteins: Chromosomal Organizers from
      Bacteria to Human" (SMC2017) was held in Nanyo City, Yamagata, Japan, from 13 to
      16 June 2017. The meeting was attended by 134 participants (among them, 76 from
      outside of Japan) who were interested in one of the highly conserved classes of
      chromosomal proteins regulating large-scale chromosome structure and function. A
      keynote lecture was followed by 41 oral presentations and 71 poster presentations
      in the four-day meeting. Diverse topics surrounding eukaryotic SMC protein
      complexes (cohesins, condensins and SMC5/6) and prokaryotic SMCs, and a wide
      range of cutting-edge approaches (from polymer physics through medical genetics)
      were presented. Dominant themes discussed in the meeting included mechanistically
      how the SMC protein complexes might form chromatin loops and domains. The
      participants enjoyed both exciting debate about chromosome organization and warm
      welcome offered by local people in a small city located in the northern part of
      Japan.

PMID- 29067762
TI  - Study on the interaction between cannabinol and DNA using acridine orange as a
      fluorescence probe.
AB  - The interaction between cannabinol (CBN) and herring-sperm deoxyribonucleic acid
      was investigated by using acridine orange as a fluorescence probe in this work.
      UV-Vis spectroscopy, fluorescence spectroscopy, and DNA melting techniques were
      used. The fluorescence of DNA acridine orange was quenched by CBN. The results
      indicated that CBN can bind to DNA. The binding constant for the CBN and herring
      sperm deoxyribonucleic acid was obtained at 3 temperatures, respectively. Results
      of molecular docking corroborated the experimental results obtained from
      spectroscopic investigations. The influence of ionic strength on the fluorescence
      properties was also investigated. The thermodynamic results indicated that
      hydrophobic interaction played a major role in the binding between CBN and DNA.

PMID- 29067761
TI  - What have we learned about heart failure with mid-range ejection fraction one
      year after its introduction?
AB  - The 2016 European Society of Cardiology heart failure guidelines introduced the
      term 'heart failure with mid-range ejection fraction' (HFmrEF) to refer to
      patients with heart failure and a mildly reduced ejection fraction of 40-49%.
      About 20% of heart failure patients fall in this category. One of the main
      reasons for the introduction of this category was to stimulate research into this
      grey area. This review aims to highlight the key findings that have been
      published so far. Firstly, HFmrEF more closely resembles heart failure with
      reduced (HFrEF) than preserved ejection fraction (HFpEF) with regard to ischaemic
      aetiology, which is more frequent in both HFmrEF and HFrEF compared to HFpEF.
      Secondly, changes in ejection fraction over time are common, and seem to be more
      important than baseline ejection fraction alone. Patients who progress from
      HFmrEF to HFrEF have a worse prognosis than those who remain stable or transition
      to HFpEF. Lastly, and perhaps most importantly, retrospective analyses from a
      randomized trial suggest that patients with HFmrEF seem to benefit from therapies
      that have shown to improve outcome in HFrEF, whereas no such benefit was seen in
      patients with HFpEF.

PMID- 29067763
TI  - Weight change and pregnancy loss: what can be concluded?

PMID- 29067764
TI  - When and How to Change Career: Or the Post-Doc Dilemma.

PMID- 29067765
TI  - Identification of the Molecular Determinants of the Antibacterial Activity of
      LmutTX, a Lys49 Phospholipase A2 Homologue Isolated from Lachesis muta muta Snake
      Venom (Linnaeus, 1766).
AB  - Snake venom phospholipases A2 (PLA2 s) are responsible for numerous
      pathophysiological effects in snakebites; however, their biochemical properties
      favour antimicrobial actions against different pathogens, thus constituting a
      true source of potential microbicidal agents. This study describes the isolation
      of a Lys49 PLA2 homologue from Lachesis muta muta venom using two chromatographic
      steps: size exclusion and reverse phase. The protein showed a molecular mass of
      13,889 Da and was devoid of phospholipase activity on an artificial substrate.
      The primary structure made it possible to identify an unpublished protein from L.
      m. muta venom, named LmutTX, that presented high identity with other Lys49 PLA2 s
      from bothropic venoms. Synthetic peptides designed from LmutTX were evaluated for
      their cytotoxic and antimicrobial activities. LmutTX was cytotoxic against C2C12
      myotubes at concentrations of at least 200 MUg/mL, whereas the peptides showed a
      low cytolytic effect. LmutTX showed antibacterial activity against Gram-positive
      and Gram-negative bacteria; however, S. aureusATCC 29213 and MRSA strains were
      more sensitive to the toxin's action. Synthetic peptides were tested on S.
      aureus, MRSA and P. aeruginosaATCC 27853 strains, showing promising results. This
      study describes for the first time the isolation of a Lys49 PLA2 from Lachesis
      snake venom and shows that peptides from specific regions of the sequence may
      constitute new sources of molecules with biotechnological potential.

PMID- 29067767
TI  - Hypertensive target organ damage is better associated with central than brachial
      blood pressure: The Northern Shanghai Study.
AB  - To compare central and brachial blood pressure (BP) in the association of target
      organ damage (TOD) in a community-based elderly population, 1599 (aged 71.4 +/-
      6.1 years) participants in northern Shanghai were recruited. TOD included left
      ventricular hypertrophy (n = 1556), left ventricular diastolic dysfunction (n =
      1524), carotid plaque (n = 1558), arteriosclerosis (n = 1485), and
      microalbuminuria (n = 1516). Both central and brachial BP significantly
      correlated with TOD. In full-model regression, central BP was significantly
      associated with all TOD (P <= .04), whereas brachial BP was only significantly
      associated with left ventricular hypertrophy and arteriosclerosis (P <= .01).
      Similarly, in stepwise regression, central BP was significantly associated with
      left ventricular hypertrophy, left ventricular diastolic dysfunction,
      arteriosclerosis, and microalbuminuria (P <= .04), while brachial BP was not
      associated with any TOD. Receiver operating characteristic analyses indicated
      that central BP identified arteriosclerosis and microalbuminuria better than
      brachial BP (P <= .01). In conclusion, central BP showed superiority over
      brachial BP in the association of hypertensive TOD in a community-based elderly
      population.

PMID- 29067768
TI  - Comparative risk of new-onset diabetes mellitus for antihypertensive drugs: A
      network meta-analysis.
AB  - New-onset diabetes mellitus (NOD) refers to forms of diabetes mellitus that
      develop during the therapeutic processes of other diseases such as hypertension.
      This study has been conducted in a network meta-analysis to compare
      antihypertensive drugs by identifying both the advantages and disadvantages on
      NOD by focusing on their respective effect rates. Odd ratios and corresponding
      95% confidence intervals or credible intervals were calculated within pairwise
      and network meta-analysis. A total of 38 articles with 224 140 patients were
      included to evaluate the preventive effect of hypertension drugs on NOD. From the
      network meta-analysis it was evident that both angiotensin-converting enzyme
      inhibitor as well as angiotensin receptor blocker treatments are associated with
      a lower risk of developing NOD compared with placebo, with ranking probabilities
      of 79.81% and 72.77%, respectively, while beta-blockers and calcium channel
      blockers may significantly increase the probability of developing NOD (beta
      blockers: odds ratio, 2.18 [95% credible intervals: 1.36-3.50]; calcium channel
      blockers: odds ratio, 1.16 [95% credible intervals, 1.05-1.29]). In conclusion,
      angiotensin receptor blockers have an advantage over the other treatments
      regarding the NOD.

PMID- 29067766
TI  - MolProbity: More and better reference data for improved all-atom structure
      validation.
AB  - This paper describes the current update on macromolecular model validation
      services that are provided at the MolProbity website, emphasizing changes and
      additions since the previous review in 2010. There have been many infrastructure
      improvements, including rewrite of previous Java utilities to now use existing or
      newly written Python utilities in the open-source CCTBX portion of the Phenix
      software system. This improves long-term maintainability and enhances the
      thorough integration of MolProbity-style validation within Phenix. There is now a
      complete MolProbity mirror site at http://molprobity.manchester.ac.uk. GitHub
      serves our open-source code, reference datasets, and the resulting multi
      dimensional distributions that define most validation criteria. Coordinate output
      after Asn/Gln/His "flip" correction is now more idealized, since the post
      refinement step has apparently often been skipped in the past. Two distinct sets
      of heavy-atom-to-hydrogen distances and accompanying van der Waals radii have
      been researched and improved in accuracy, one for the electron-cloud-center
      positions suitable for X-ray crystallography and one for nuclear positions. New
      validations include messages at input about problem-causing format
      irregularities, updates of Ramachandran and rotamer criteria from the million
      quality-filtered residues in a new reference dataset, the CaBLAM Calpha-CO
      virtual-angle analysis of backbone and secondary structure for cryoEM or low
      resolution X-ray, and flagging of the very rare cis-nonProline and twisted
      peptides which have recently been greatly overused. Due to wide application of
      MolProbity validation and corrections by the research community, in Phenix, and
      at the worldwide Protein Data Bank, newly deposited structures have continued to
      improve greatly as measured by MolProbity's unique all-atom clashscore.

PMID- 29067770
TI  - Assessment of left atrial function: Another window to detect early cardiac
      impairment?

PMID- 29067769
TI  - Differences in skeletal muscle loss caused by cytotoxic chemotherapy and
      molecular targeted therapy in patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: Recent studies have revealed a reduction in the skeletal muscle area
      in patients with advanced non-small cell lung cancer (NSCLC) after chemotherapy.
      EGFR and ALK tyrosine kinase inhibitor (TKI)-based therapies are less cytotoxic
      than chemotherapy, but differences in skeletal muscle mass between patients
      receiving EGFR and ALK TKI therapies and patients receiving cytotoxic
      chemotherapy have not yet been reported. METHODS: Data of pathologically proven
      NSCLC patients were reviewed, and chest computed tomography and/or positron
      emission tomography-computed tomography images obtained from January 2012 to
      December 2014 were selected. Patients were divided into two groups: cytotoxic
      chemotherapy (CG) and molecular targeted (MG). Muscle mass was measured with a
      single cross-sectional area of the muscle at the third lumber vertebra (L3MA). To
      estimate skeletal muscle changes during chemotherapy, we defined the following L3
      skeletal muscle index (L3SMI) ratio: post L3SMI/pre L3SMI. Differences in the SMI
      ratio between the groups were evaluated using the Wilcoxon signed-rank test.
      RESULTS: Sixty-five patients were included in this study: 44 patients received
      cytotoxic chemotherapy and 21 received molecular targeted therapy (EGFR and ALK
      TKI). The loss of L3MA in the CG was higher than in the MG (P = 0.03). In the CG,
      the L3SMI ratio defined to evaluate skeletal muscle mass changes was
      significantly lower than in the MG (P = 0.0188). CONCLUSION: Our results suggest
      that skeletal muscle loss during first-line therapy was significantly different
      between patients receiving cytotoxic chemotherapy and those receiving TKIs.
      Specifically, skeletal muscle loss was lower in patients receiving TKIs than in
      patients receiving cytotoxic chemotherapy.

PMID- 29067772
TI  - High mortality and enhanced recovery: modelling the countervailing effects of
      disturbance on population dynamics.
AB  - Disturbances cause high mortality in populations while simultaneously enhancing
      population growth by improving habitats. These countervailing effects make it
      difficult to predict population dynamics following disturbance events. To address
      this challenge, we derived a novel form of the logistic growth equation that
      permits time-varying carrying capacity and growth rate. We combined this equation
      with concepts drawn from disturbance ecology to create a general model for
      population dynamics in disturbance-prone systems. A river flooding example using
      three insect species (a fast life-cycle mayfly, a slow life-cycle dragonfly and
      an ostracod) found optimal tradeoffs between disturbance frequency vs. magnitude
      and a close fit to empirical data in 62% of cases. A savanna fire analysis
      identified fire frequencies of 3-4 years that maximised population size of a
      perennial grass. The model shows promise for predicting population dynamics after
      multiple disturbance events and for management of river flows and fire regimes.

PMID- 29067771
TI  - Arterial stiffness, sex, and age difference on hypertensive response to supine
      bicycle exercise.
AB  - Contributors to a hypertensive response to exercise (HTR) according to sex and
      age have not been fully evaluated. The authors analyzed a database of supine
      bicycle exercise stress echocardiography findings. HTR was defined as peak
      systolic blood pressure >=210 mmHg for men and >=190 mmHg for women during
      exercise. A total of 797 patients (306 [38%] women) were analyzed, with a mean
      age of 64 +/- 10 years. Female sex, hypertension; higher left ventricular
      ejection fraction, effective arterial elastance, and pulse wave velocity; and
      lower total arterial compliance were significantly related to HTR. Patients with
      HTR had higher relative wall thickness, ratio of early diastolic mitral inflow
      and annular velocity, and diastolic elastance (all P <= .05). In multivariable
      analysis, indices of arterial stiffness such as pulse wave velocity, arterial
      elastance, total arterial compliance, and systemic vascular resistance were more
      strongly related in women, while in men, index of sympathetic activation was
      additionally related to HTR (all P <= .05). Female sex and lower total arterial
      compliance in older patients (>=65 years) and higher systemic vascular resistance
      and left ventricular relative wall thickness in younger patients were more
      strongly related to HTR. In conclusion, HTR was related to arterial stiffness,
      sympathetic activation, and diastolic dysfunction; however, the associations were
      different according to sex and age, which might guide individualized therapy.

PMID- 29067773
TI  - Short-term blood pressure variability in acute coronary syndrome.

PMID- 29067774
TI  - Recellularization of well-preserved decellularized kidney scaffold using adipose
      tissue-derived stem cells.
AB  - To establish a recellularization kidney model by using adipose tissue-derived
      stem cells (ADSCs) as seeding cells and to investigate the growth and
      differentiation of ADSCs in decellularized kidney scaffolds. ADSCs were isolated
      using a modified method and then identified using flow cytometry analysis.
      Osteogenesis and adipogenesis differentiation were performed. Rat kidneys were
      decellularized using 0.5% sodium dodecyl sulfate. Immunofluorescence,
      immunohistochemistry, and scanning electron microscope were conducted to examine
      the scaffold microstructure. The decellularized kidney scaffold was seeded with
      ADSCs antegrade through the artery or retrograde through the ureter and cultured
      for 5-10 days. Hematoxylin and eosin staining, immunofluorescence, and
      immunohistochemistry were applied to assess growth and differentiation of seeding
      cells within the scaffold. ADSCs populated within the glomerular, vascular, and
      tubular area of kidney scaffolds. Cells differentiated toward endothelial or
      tubular cells. Stromal cell-derived factor 1 promoted cell attachment in the
      scaffold. These findings suggest that ADSCs can be used as an additional new
      source of seeding cells within decellularized kidney scaffold. This combination
      may offer an alternative to donor kidney transplant. In this way, autologous
      ADSCs can be utilized as seeding cells in cell-scaffold kidney regeneration for
      further clinical transplantation. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater
      Res Part A: 106A: 805-814, 2018.

PMID- 29067776
TI  - Exercise-induced benefits in metabolic syndrome.

PMID- 29067775
TI  - Dual-phase hybrid 18 F-Fluoride Positron emission tomography/MRI in ankylosing
      spondylitis: Investigating the link between MRI bone changes, regional hyperaemia
      and increased osteoblastic activity.
AB  - INTRODUCTION: Focal 18 F-Fluoride uptake on blood-pool phase PET represents
      regional hyperaemia, while it indicates osteoblastic activity on mineralization
      phase PET. This study investigates the link between regional hyperaemia and
      osteoblastic activity in inflammatory and chronic lesions of ankylosing
      spondylitis (AS) of the sacroiliac joints (SIJ) using dual-phase 18 F-Fluoride
      PET/MRI. METHODS: Thirteen patients (six men, seven women, age: 37 +/- 10 years)
      with active AS prospectively underwent dual-phase 18 F-Fluoride PET/MRI. Blood
      pool phase PET was acquired 6 min and mineralization phase PET 40 min after
      injection of 158 +/- 8 MBq 18 F-Fluoride. SIJ quadrants (SQ) were assessed
      regarding inflammatory lesions represented by bone marrow oedema (BME), chronic
      AS lesions such as erosion, fat deposition (FD), sclerosis and ankylosis on MRI,
      and regarding focal 18 F-Fluoride uptake on both PET datasets. Image quality (IQ)
      of both PET datasets and MRI was evaluated using a 4-point Likert scale. RESULTS:
      Of 104 SQ, there were 63.4% SQ with FD, 42.3% SQ with BME, 26.9% SQ with
      erosions, 26% SQ with sclerosis and 10.6% SQ with ankylosis. BME alone was
      associated with focal 18 F-Fluoride uptake in 63.6% SQ on blood-pool phase and
      90.9% SQ on mineralization phase 18 F-Fluoride PET/MRI. Instead, FD, erosion,
      sclerosis, ankylosis were not associated with focal 18 F-Fluoride uptake on
      either blood-pool or mineralization phase 18 F-Fluoride PET/MRI. SQ showing BME
      alone or a combination of BME and chronic AS lesions had a significantly higher
      percentage of focal 18 F-Fluoride uptake on blood-pool phase and mineralization
      phase PET/MRI than SQ showing AS lesions without BME (P < 0.001). Both 18 F
      Fluoride PET datasets provided high IQ, albeit IQ of mineralization phase PET was
      superior to blood-pool phase PET (P < 0.001). CONCLUSION: Dual-phase 18 F
      Fluoride PET/MRI of the SIJ showed that inflammatory rather than chronic AS
      lesions are associated with regional hyperaemia and osteoblastic activity.

PMID- 29067777
TI  - Surface modification of bulk titanium substrates for biomedical applications via
      low-temperature microwave hydrothermal oxidation.
AB  - Micro-to-nanoscale surface topographies of orthopaedic and dental implants can
      affect fluid wetting and biological response. Nanoscale features can be
      superimposed on microscale roughness of titanium (Ti) surfaces at high
      temperatures, resulting in increased osteoblast differentiation. However, high
      temperatures can compromise mechanical properties of the bulk material. Here, we
      have developed a novel low-temperature microwave hydrothermal (MWHT) oxidation
      process for nanomodification of microrough (SLA) Ti surfaces. Nanoscale
      protuberances (20 -100 nm average diameter) were generated on SLA surfaces via
      MWHT treatment at 200 degrees C in H2 O, or in aqueous solutions of H2 O2 or NH4
      OH, for times ranging from 1 to 40 h. The size, shape, and crystalline content of
      the nanoprotuberances varied with the solution used and treatment time. The
      hydrophilicity of all MWHT-modified surfaces was dramatically enhanced. MG63 and
      normal human osteoblasts (NHOsts) were cultured on MWHT-treated SLA surfaces.
      While most responses to MWHT-modified surfaces were comparable to those seen on
      SLA controls, the MWHT-generated nanotopography reduced osteocalcin production by
      NHOst cells, suggesting that specific nanotopographic characteristics
      differentially mediate osteoblast phenotypic expression. MWHT processing provides
      a scalable, low-temperature route for tailoring nanoscale topographies on
      microroughened titanium implant surfaces with significantly enhanced wetting by
      water, without degrading the microscale surface structure of such implants. (c)
      2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 782-796, 2018.

PMID- 29067778
TI  - Dentists' Most Common Practices when Selecting an Implant System.
AB  - PURPOSE: To report a comprehensive description of dental implant system selection
      practices among dentists practicing implantology worldwide. MATERIALS AND
      METHODS: An online questionnaire was designed and sent to members of 15 dental
      implant organizations. The survey questions addressed: dental implant system
      selection criteria, implant design variables, dentists' perspective to implant
      quality stamps, and dentists' satisfaction with their implant system(s).
      Responses were compiled and analyzed to determine correlation of responses using
      the chi-squared test (level of significance alpha <= 0.05). RESULTS: Out of 4264
      invitations sent, a total of 2001 (response rate = 46.9%) dentists participated
      in the survey. Approximately half of survey respondents (48.7%) were general
      dentists. More than two-thirds of the survey respondents (72.5%) were performing
      both the surgical and prosthetic implant phases. Implant-abutment connections
      were the most important dental implant system selection criterion (84.7%),
      followed by scientific evidence available on the implant system (82.8%), and
      simplicity of prosthetic steps (81.4%). Patient preferences (19.8%) were rated as
      the least important aspect. Sandblasted large gritted acid etched implant
      surfaces (SLA) were the most commonly used implant surfaces (75.8%); fluoride
      coated surfaces were the least commonly used (15.4%). CONCLUSION: According to
      the results of this survey, most survey respondents practiced both surgical and
      prosthetic phases of dental implantology. The majority of survey respondents
      agreed on the importance of implant-abutment connections, scientific evidence
      available on implant systems, and simplicity of prosthetic steps when selecting
      implant systems.

PMID- 29067779
TI  - An Antibacterial beta-Lactone Kills Mycobacterium tuberculosis by Disrupting
      Mycolic Acid Biosynthesis.
AB  - The spread of antibiotic resistance is a major challenge for the treatment of
      Mycobacterium tuberculosis infections. In addition, the efficacy of drugs is
      often limited by the restricted permeability of the mycomembrane. Frontline
      antibiotics inhibit mycomembrane biosynthesis, leading to rapid cell death.
      Inspired by this mechanism, we exploited beta-lactones as putative mycolic acid
      mimics to block serine hydrolases involved in their biosynthesis. Among a
      collection of beta-lactones, we found one hit with potent anti-mycobacterial and
      bactericidal activity. Chemical proteomics using an alkynylated probe identified
      Pks13 and Ag85 serine hydrolases as major targets. Validation through enzyme
      assays and customized 13 C metabolite profiling showed that both targets are
      functionally impaired by the beta-lactone. Co-administration with front-line
      antibiotics enhanced the potency against M. tuberculosis by more than 100-fold,
      thus demonstrating the therapeutic potential of targeting mycomembrane
      biosynthesis serine hydrolases.

PMID- 29067780
TI  - After-hours/on-call experience during primary care nurse practitioner education
      utilizing standard scenarios and simulated patients.
AB  - BACKGROUND AND PURPOSE: Few nurse practitioner (NP) programs include an after
      hours/on-call component in their clinical preparation of NP students. This role
      is expected in many primary and specialty care practices, and is one that
      students feel unprepared to competently navigate. METHODS: Utilizing simulated
      callers as patients or parents, NP students participated in a simulated after
      hours/on-call experience that included receiving the call, managing the patient,
      and submitting documentation of the encounter. Students completed pre- and
      postparticipation evaluations, and were evaluated by the simulated patient
      callers and faculty using standardized evaluation tools. CONCLUSIONS: NP students
      rated the experience as an educationally valuable experience despite feeling
      anxious and nervous about the experience. Several essential skills were
      identified including critical thinking, clear communication, self-confidence, and
      access to resources. After participation NP students were more receptive to an NP
      position with an on-call component. IMPLICATIONS FOR PRACTICE: Inclusion of a
      simulated on-call experience is a feasible component of NP education and should
      be added to the NP curriculum.

PMID- 29067782
TI  - A tribute to Anna Tramontano (1957-2017).

PMID- 29067781
TI  - Report of the International Stem Cell Banking Initiative Workshop Activity:
      Current Hurdles and Progress in Seed-Stock Banking of Human Pluripotent Stem
      Cells.
AB  - This article summarizes the recent activity of the International Stem Cell
      Banking Initiative (ISCBI) held at the California Institute for Regenerative
      Medicine (CIRM) in California (June 26, 2016) and the Korean National Institutes
      for Health in Korea (October 19-20, 2016). Through the workshops, ISCBI is
      endeavoring to support a new paradigm for human medicine using pluripotent stem
      cells (hPSC) for cell therapies. Priority considerations for ISCBI include
      ensuring the safety and efficacy of a final cell therapy product and quality
      assured source materials, such as stem cells and primary donor cells. To these
      ends, ISCBI aims to promote global harmonization on quality and safety control of
      stem cells for research and the development of starting materials for cell
      therapies, with regular workshops involving hPSC banking centers, biologists, and
      regulatory bodies. Here, we provide a brief overview of two such recent
      activities, with summaries of key issues raised. Stem Cells Translational
      Medicine 2017;6:1956-1962.

PMID- 29067784
TI  - Interpretation of low reactivity in the Abbott Architect rHTLV I/II assay.
AB  - OBJECTIVE: The objective of this study is to reduce donor tissue wastage. AIM:
      The aim of this study is to determine, in the case of the Abbott Architect rHTLV
      I/II assay, whether a signal/cut-off (S/CO) ratio higher than the manufacturer's
      recommendation of 1.0 could be applied to diagnose significant HTLV-1
      seroreactivity. BACKGROUND: The detection of human T cell leukaemia virus type 1
      (HTLV-1) infection is primarily based on serology often utilising random access
      platforms. Although current assays have high sensitivity and specificity, in low
      prevalence regions, significant numbers of false-positive reactions occur. A
      comprehensive follow-up is difficult within the time frame of organ donation.
      This can lead to donor tissue wastage. METHODS: A retrospective analysis of 12
      250 samples previously tested on the Abbott Architect rHTLV I/II platform and
      further tested by confirmatory serology/molecular detection to determine the
      sensitivity and positive predictive value in the S/CO ratio range was conducted.
      RESULTS: Where the sample S/CO ratio was >20 (n = 498), HTLV infection was
      confirmed in all but eight subjects. All of these eight had indeterminate
      confirmatory results, and none were found to be uninfected. Conversely, in the
      samples within the S/CO ratio range 1-4 (n = 271), no subject was subsequently
      found to be HTLV-infected although HTLV infection could not be excluded in all
      cases, primarily due to lack of follow-up samples (n = 60/271). CONCLUSIONS:
      Samples with an S/CO ratio of <4.0 on the Abbott Architect rHTLV I/II platform
      represent a low risk of HTLV infection in the UK, and organs from such donors
      might reasonably be considered for transplantation, within the context of
      appropriate risk-benefit assessment.

PMID- 29067783
TI  - Both hemispheric influenza vaccine recommendations would have missed near half of
      the circulating viruses in Madagascar.
AB  - BACKGROUND: Influenza immunization still poses a critical challenge globally and
      specifically for tropical regions due to their complex influenza circulation
      pattern. Tropical regions should select the WHO's Northern Hemisphere or Southern
      Hemisphere recommended vaccine composition based on local surveillance. Analyses
      of influenza immunization effectiveness have neglected to account for the
      proportion of circulating viruses prevented from causing infection each year. We
      investigate this question for Madagascar, where influenza vaccines are not widely
      available. METHODS: Seventy-eight Malagasy influenza strains characterized from
      2002 to 2014 were challenged with hypothetical scenarios in which the WHO's
      Northern Hemisphere and Southern Hemisphere recommended vaccine compositions were
      provided to the population. Match between circulating and vaccine strains was
      determined by haemagglutination inhibition assays. Strain-specific positive
      matches were scored assuming 9 months of protection, and scenarios incorporated
      vaccine delays from zero to 5 months. RESULTS: Malagasy influenza strains matched
      54% and 44%, respectively, with the Northern Hemisphere and Southern Hemisphere
      recommended vaccine strains when the vaccine was delivered as soon as available.
      The matching values further decreased when additional delivery and application
      delays were considered. Differences between recommended compositions were not
      statistically significant. CONCLUSION: Our results showed matching with the
      Northern Hemisphere vaccine barely above 50%, even in the more favourable
      scenario. This suggests that if implemented, routine influenza vaccines would not
      provide an optimal protection against half of the influenza strains circulating
      in any epidemic season of Madagascar. We suggest that this limitation in
      influenza vaccine efficacy deserves greater attention, and should be considered
      in cost/benefit analyses of national influenza immunization programmes.

PMID- 29067786
TI  - Long-term safety of different antihypertensive regimens: The risk of unfair
      comparisons.

PMID- 29067785
TI  - Pre-hospital transfusion of red blood cells in civilian trauma patients.
AB  - INTRODUCTION: The current management of severely injured patients includes damage
      control resuscitation strategies that minimise the use of crystalloids and
      emphasise earlier transfusion of red blood cells (RBC) to prevent coagulopathy.
      In 2012, London's air ambulance (LAA) became the first UK civilian pre-hospital
      service to routinely carry RBC to the trauma scene. OBJECTIVE: To investigate the
      effect of pre-hospital RBC transfusion (phRTx) on overall blood product
      consumption. METHODS: A retrospective trauma database study compares before
      implementation with after implementation of phRTx in exsanguinating trauma
      patients transported directly to one major trauma centre. Pre-hospital deaths
      were excluded. Univariate and multivariate Poisson regression analyses on data
      subject to multiple imputation were conducted. RESULTS: We included 137 and 128
      patients in the before and after the implementation of phRTx groups,
      respectively. LAA transfused 304 RBC units (median 2, inter quartile range 1-3).
      We found a significant reduction in total RBC usage and reduced early use of
      platelets and fresh-frozen plasma (FFP) after the implementation of phRTx in both
      univariate (P < 0.001) and multivariate analyses (P < 0.001). No immediate
      adverse transfusion reactions were identified. CONCLUSION: Pre-hospital trauma
      transfusion practice is feasible and associated with overall reduced RBC,
      platelets and FFP consumption.

PMID- 29067787
TI  - Impact of Removable Partial Dental Prostheses on the Oral Health-Related Quality
      of Life of a South African Cohort with Varied Distributions of Missing Posterior
      Teeth.
AB  - PURPOSE: To determine the impact of removable partial dental prostheses on
      satisfying the daily functioning and quality of life (QoL) of adult patients with
      different distributions of missing posterior teeth. MATERIALS AND METHODS: A
      cross-sectional interventional study was carried out on 80 patients having
      variously distributed posteriorly shortened and interrupted arches. Treatment
      comprised provision of partial dentures by senior dental students, supervised by
      senior clinical teachers who had knowledge of the potential benefits of the
      shortened dental arch (SDA) concept. The Oral Impacts on Daily Performance Index
      was completed before and 6 months after prosthetic treatment across groups
      comprising Kennedy Classes I, II, and III arches. Analysis included descriptive
      statistics and associations and comparisons between variables. RESULTS: Mean age
      of patients was 57.4 years (SD = 13.1), many were retired (72.2%), and a majority
      were females (60%). Most patients lived in urban areas (95%), and were largely
      unemployed (63.3%). At pretreatment, only 31.3% of patients reported having good
      dental health and satisfaction with their current oral state, while 82.5% said
      they had a great need for treatment. The negative oral impacts that were most
      frequently experienced were those of eating (67.5%), smiling (50%), and being
      emotionally disturbed (63.8%). Post-treatment, 76.3% indicated good oral health
      and satisfaction with no significant differences between the 3 Kennedy groups.
      Any further negative impacts were reported mostly for Kennedy Classes I and II.
      CONCLUSIONS: Overall, significant reductions of negative impacts were observed
      following treatment with dentures, across the 3 Kennedy groups, with respect to
      improved function, satisfaction, and oral health-related QoL. The findings
      confirm the reliance by partially dentate patients in all 3 Kennedy groups on
      dentures for improved oral health, although the possible benefits of the SDA
      concept as an alternative treatment option was not specifically explored.

PMID- 29067788
TI  - PGC-1alpha affects aging-related changes in muscle and motor function by
      modulating specific exercise-mediated changes in old mice.
AB  - The age-related impairment in muscle function results in a drastic decline in
      motor coordination and mobility in elderly individuals. Regular physical activity
      is the only efficient intervention to prevent and treat this age-associated
      degeneration. However, the mechanisms that underlie the therapeutic effect of
      exercise in this context remain unclear. We assessed whether endurance exercise
      training in old age is sufficient to affect muscle and motor function. Moreover,
      as muscle peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (PGC-1alpha) is a key regulatory hub in endurance exercise adaptation with
      decreased expression in old muscle, we studied the involvement of PGC-1alpha in
      the therapeutic effect of exercise in aging. Intriguingly, PGC-1alpha muscle
      specific knockout and overexpression, respectively, precipitated and alleviated
      specific aspects of aging-related deterioration of muscle function in old mice,
      while other muscle dysfunctions remained unchanged upon PGC-1alpha modulation.
      Surprisingly, we discovered that muscle PGC-1alpha was not only involved in
      improving muscle endurance and mitochondrial remodeling, but also phenocopied
      endurance exercise training in advanced age by contributing to maintaining
      balance and motor coordination in old animals. Our data therefore suggest that
      the benefits of exercise, even when performed at old age, extend beyond skeletal
      muscle and are at least in part mediated by PGC-1alpha.

PMID- 29067789
TI  - The New Acetylcholinesterase Inhibitors PC-37 and PC-48 (7-Methoxytacrine
      Donepezil-Like Compounds): Characterization of Their Metabolites in Human Liver
      Microsomes, Pharmacokinetics and In Vivo Formation of the Major Metabolites in
      Rats.
AB  - The objective of this study was to elucidate the pharmacokinetics and metabolite
      formation of newly developed non-selective AChE/BChE 7-MEOTA-donepezil-like
      inhibitors for potential therapeutic use in Alzheimer's disease (AD) patients.
      The chemical structures of metabolites were defined during incubation with human
      liver microsomes, and subsequently, the metabolization was verified in in vivo
      study. In vitro metabolic profiling revealed the formation of nine major
      metabolites in the case of PC-37 and eight metabolites of PC-48. Hydroxylation
      and the enzymatic hydrolysis of bonds close to the piperazine ring appeared to be
      the principal metabolic pathways in vitro. Of these metabolites, M1-M7 of PC-37
      and M1-M6 of PC-48 were confirmed under in vivo conditions. Pilot pharmacokinetic
      experiments in rats were focused on the absorption, distribution and elimination
      of these compounds. Absorption after i.m. application was relatively fast; the
      bioavailability expressed as AUCtotal was 28179 +/- 4691 min.ng/mL for PC-37 and
      23374 +/- 4045 min.ng/mL for PC-48. Both compounds showed ability to target the
      central nervous system, with brain concentrations exceeding those in plasma. The
      maximal brain concentrations are approximately two times higher than the plasma
      concentrations. The relatively high brain concentrations persisted throughout the
      experiment until 24 hr after application. Elimination via the kidneys (urine)
      significantly exceeded elimination via the liver (bile). All these
      characteristics are crucial for new candidates intended for AD treatment. The
      principle metabolic pathways that were verified in the in vivo study do not show
      any evidence for formation of extremely toxic metabolites, but this needs to be
      confirmed by further studies.

PMID- 29067790
TI  - Sirt2-BubR1 acetylation pathway mediates the effects of advanced maternal age on
      oocyte quality.
AB  - The level of Sirt2 protein is reduced in oocytes from aged mice, while exogenous
      expression of Sirt2 could ameliorate the maternal age-associated meiotic defects.
      To date, the underlying mechanism remains unclear. Here, we confirmed that
      specific depletion of Sirt2 disrupts maturational progression and
      spindle/chromosome organization in mouse oocytes, with compromised kinetochore
      microtubule attachments. Candidate screening revealed that acetylation state of
      lysine 243 on BubR1 (BubR1-K243, an integral part of the spindle assembly
      checkpoint complex) functions during oocyte meiosis, and acetylation-mimetic
      mutant BubR1-K243Q results in the very similar phenotypes as Sirt2-knockdown
      oocytes. Furthermore, we found that nonacetylatable-mimetic mutant BubR1-K243R
      partly prevents the meiotic deficits in oocytes depleted of Sirt2. Importantly,
      BubR1-K243R overexpression in oocytes derived from aged mice markedly suppresses
      spindle/chromosome anomalies and thereupon lowers the incidence of aneuploid
      eggs. In sum, our data suggest that Sirt2-dependent BubR1 deacetylation involves
      in the regulation of meiotic apparatus in normal oocytes and mediates the effects
      of advanced maternal age on oocyte quality.

PMID- 29067792
TI  - Enhanced hepatogenic differentiation of bone marrow derived mesenchymal stem
      cells on liver ECM hydrogel.
AB  - Bone marrow derived mesenchymal stem cells (BM-MSC) is a promising alternative
      cell source to primary hepatocytes because of their ability to differentiate into
      hepatocyte-like cells. However, their inability to differentiate efficiently and
      potential to turn into myofibroblasts restrict their applications. This study
      developed a plate coating from the liver extracellular matrix (ECM) and
      investigated its ability in facilitating the BM-MSCs proliferation, hepatic
      differentiation, and hepatocyte-specific functions during in vitro culture. After
      28-day culture, BM-MSCs on the ECM coating showed hepatocyte-like morphology, and
      certain cells took up low-density lipoprotein. Synthesis of albumin, urea, and
      anti-alpha-fetoprotein, as well as expression of certain hepatic markers, in
      cells cultured on ECM were higher than cells cultured on non-coated and Matrigel
      coated plates. mRNA levels of CYP3A4, albumin, CK18, and CYP7A1 in cells on ECM
      coating were significantly higher than cells cultured on the non-coating
      environment. In conclusion, viability and hepatogenic differentiation of BM-MSCs
      cultured on both Matrigel and ECM coating were significantly enhanced compared
      with those cultured on non-coated plates. Moreover, the liver ECM coating induced
      additional metabolic functions relative to the Matrigel coating. The liver ECM
      hydrogel preserves the natural composition, promotes simple gelling, induces
      efficient stem cell hepatogenic differentiation, and may have uses as an
      injectable intermedium for hepatocytes. (c) 2017 Wiley Periodicals, Inc. J Biomed
      Mater Res Part A: 106A: 829-838, 2018.

PMID- 29067791
TI  - Asynchrony among local communities stabilises ecosystem function of
      metacommunities.
AB  - Temporal stability of ecosystem functioning increases the predictability and
      reliability of ecosystem services, and understanding the drivers of stability
      across spatial scales is important for land management and policy decisions. We
      used species-level abundance data from 62 plant communities across five
      continents to assess mechanisms of temporal stability across spatial scales. We
      assessed how asynchrony (i.e. different units responding dissimilarly through
      time) of species and local communities stabilised metacommunity ecosystem
      function. Asynchrony of species increased stability of local communities, and
      asynchrony among local communities enhanced metacommunity stability by a wide
      range of magnitudes (1-315%); this range was positively correlated with the size
      of the metacommunity. Additionally, asynchronous responses among local
      communities were linked with species' populations fluctuating asynchronously
      across space, perhaps stemming from physical and/or competitive differences among
      local communities. Accordingly, we suggest spatial heterogeneity should be a
      major focus for maintaining the stability of ecosystem services at larger spatial
      scales.

PMID- 29067793
TI  - Nanostructured gemini-based supramolecular solvent coupled with ultrasound
      assisted back extraction as a preconcentration step before GC-MS.
AB  - Liquid-phase microextraction based on gemini-based supramolecular solvent was
      successfully applied as a preconcentration step before gas chromatography with
      mass spectrometry. To eliminate the interferences of gemini surfactant, the
      analytes were back-extracted into an immiscible organic solvent in the presence
      of ultrasonic sound waves. Three phthalate esters (di-n-butyl-, butylbenzyl-,
      bis(2-ethylhexyl)-, and di-n-octyl phthalatic esters) were used as target
      analytes. The effective parameters on extraction efficiency of the target
      analytes (i.e., the amount of surfactant and volume of propanol as major
      components making up the supramolecular solvent, ionic strength, hexane volume,
      and ultrasound time) were investigated and optimized by a one-variable-at-a-time
      method. Under the optimum conditions, the preconcentration factors of the
      analytes were in the range of 95-182. The linear dynamic range of 0.05-200.00
      MUg/L with a correlation of determination of (R2 ) >= 0.9935 was obtained. The
      proposed method had an excellent limit of detection (S/N = 3) of 0.01 for di-n
      octyl and 0.02 MUg/L for butylbenzyl- and di-n-butyl-phthalatic ester. Good
      relative recoveries in the range of 85.7-105.2% guaranteed the accuracy of the
      amount of phthalates distinguished in the nonspiked samples.

PMID- 29067795
TI  - Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL
      amyloidosis.
AB  - AIMS: To evaluate the influence of endomyocardial biopsy (EMB)-proven
      intramyocardial inflammation on mortality in patients with cardiac transthyretin
      amyloid (ATTR) or amyloid light-chain (AL) amyloidosis. METHODS AND RESULTS: We
      included 54 consecutive patients (mean age 68.83 +/- 9.59 years; 45 men) with EMB
      proven cardiac amyloidosis. We followed up patients from first diagnostic biopsy
      to as long as 36 months (mean 11.5 +/- 12 months) and compared their outcome with
      information on all-cause mortality with or without proof of inflammation on EMB.
      Intramyocardial inflammation was assessed by quantitative immunohistology.
      Patients suffering from amyloidosis revealed a significant poor prognosis with
      proof of intramyocardial inflammation in contrast to those without inflammation
      (log-rank P = 0.019). Re-grouping of patients indicated AL amyloidosis to have a
      significant impact on all-cause mortality (log-rank P = 0.012). The detailed
      subgroup analysis showed that patients suffering from AL amyloidosis with
      intramyocardial inflammation have a significantly worse prognosis compared with
      AL amyloidosis without inflammation and ATTR with or without inflammation,
      respectively (log-rank P = 0.014, contingency Fisher's exact test, P = 0.008).
      CONCLUSION: Our study reports for the first time a high incidence (48.1%) of
      intramyocardial inflammation in a series of patients with EMB-proven cardiac
      amyloidosis and could show that in patients with AL amyloidosis, intramyocardial
      inflammation correlated significantly with increased mortality. Our data have a
      direct clinical impact because one can hypothesize that additional
      immunomodulating/anti-inflammatory treatment regimens in patients with biopsy
      proven inflammation of heart muscle tissue could be beneficial for patients
      suffering from cardiac AL amyloidosis.

PMID- 29067797
TI  - Occurrence of Methylmercury in Rice-Based Infant Cereals and Estimation of Daily
      Dietary Intake of Methylmercury for Infants.
AB  - Recent reports of elevated levels of methylmercury (MeHg) in rice revealed the
      possible occurrence of MeHg in infant rice cereals, leading to potential MeHg
      exposure through cereal consumption. Total mercury (THg) and MeHg levels in 119
      infant cereal samples commonly marketed in the United States and China and
      estimated daily intake of MeHg through cereal consumption were determined.
      Concentrations of THg and MeHg in the tested cereal samples ranged from 0.35 to
      15.9 MUg/kg and from 0.07 to 13.9 MUg/kg with means of 2.86 and 1.61 MUg/kg,
      respectively. Rice-based cereals contained MeHg levels significantly higher than
      those of nonrice cereals, indicating that MeHg in rice could be source of MeHg in
      cereals. Cereal consumption could be a potential pathway of MeHg exposure for
      infants, as the EDI through cereal consumption amounted to 4-122% of the MeHg
      reference dose, suggesting the necessity of further evaluation of the potential
      health risk of dietary MeHg exposure to infants.

PMID- 29067796
TI  - Risk Factors of and Treatments for Pharyngocutaneous Fistula Occurring after
      Oropharynx and Hypopharynx Reconstruction.
AB  - BACKGROUND: A pharyngocutaneous fistula is a common and difficult-to-manage
      complication after head and neck reconstruction. It can lead to serious
      complications such as flap failure, carotid artery rupture, and pharyngeal
      stricture, and may require additional surgery. Previous radiotherapy, a low serum
      albumin level, and a higher T stage have been proposed as contributing factors.
      We aimed to clarify the risk factors for pharyngocutaneous fistula in patients
      who underwent flap reconstruction and to describe our experiences in treating
      pharyngocutaneous fistula. METHODS: Squamous cell carcinoma cases that underwent
      flap reconstruction after cancer resection from 1995 to 2013 were analyzed
      retrospectively. We investigated several significant clinical risk factors. The
      treatment modality was selected according to the size of the fistula and the
      state of the surrounding tissue, with options including conservative management,
      direct closure, flap surgery, and pharyngostoma formation. RESULTS: A total of
      127 cases (18 with fistulae) were analyzed. A higher T stage (P=0.048) and tube
      type reconstruction (P=0.007) increased fistula incidence; other factors did not
      show statistical significance (P>0.05). Two cases were treated with conservative
      management, 1 case with direct closure, 4 cases with immediate reconstruction
      using a pectoralis major musculocutaneous flap, and 11 cases with direct closure
      (4 cases) or additional flap surgery (7 cases) after pharyngostoma formation.
      CONCLUSIONS: Pharyngocutaneous fistula requires global management from prevention
      to treatment. In cases of advanced-stage cancer and tube-type reconstruction, a
      more cautious approach should be employed. Once it occurs, an accurate diagnosis
      of the fistula and a thorough assessment of the surrounding tissue are necessary,
      and aggressive treatment should be implemented in order to ensure satisfactory
      long-term results.

PMID- 29067798
TI  - Peptide Self-Assembled Nanostructures with Distinct Morphologies and Properties
      Fabricated by Molecular Design.
AB  - Six surfactant-like peptides with the same amino acid composition but different
      primary sequences are designed, including G3A3V3I3K3, K3I3V3A3G3, I3V3A3G3K3,
      K3G3A3V3I3, V3G3I3A3K3, and K3A3I3G3V3. These peptides form antiparallel beta
      sheets during self-assembly. Because the constituent residues have different side
      chain size and hydrophobicity, sequence changes adjust group distribution and
      hydrophobicity on the two sides of a given beta-sheet. This consequently tunes
      the binding energy of the side-to-side pairing conformations and leads to
      different self-assembled structures. G3A3V3I3K3 and K3I3V3A3G3 form short
      nanorods with diameters of 8.5 +/- 1.0 nm and lengths <150 nm. I3V3A3G3K3 and
      K3G3A3V3I3 form nanosheets with heights of 4.0 +/- 0.5 nm and limited lengths and
      widths. V3G3I3A3K3 and K3A3I3G3V3 form long fibrils with diameters of 7.0 +/- 1.0
      nm and lengths of micrometer scale. These nanostructures exhibit different
      capacity in encapsulating insoluble hydrophobic drug molecules and delivering
      them into the cells. The nanosheets of I3V3A3G3K3 and K3G3A3V3I3 can encapsulate
      both nile red and doxorubicin molecules to an extent of up to 17-23% in mole
      ratio. Moreover, the shape and size of the nanostructures affect the drug
      delivery into cells greatly, with the nanosheets and short rods exhibiting higher
      efficiency than the long fibrils. The study provides new insights into programmed
      peptide self-assembly toward specific functionalities.

PMID- 29067799
TI  - Three-Dimensional WO3 Nanoplate/Bi2S3 Nanorod Heterojunction as a Highly
      Efficient Photoanode for Improved Photoelectrochemical Water Splitting.
AB  - The rational design of semiconductor photoanodes with sufficient light
      absorption, efficient photogenerated carrier separation, and fast charge
      transport is crucial for photoelectrochemical (PEC) water splitting.
      Incorporating a small-band-gap semiconductor to a large-band-gap material with
      matched energy band position is a promising route to improve the light harvesting
      and charge transport. Herein, we report the fabrication of a three-dimensional
      heterojunction with uniform Bi2S3 nanorods on WO3 nanoplates by hydrothermal
      process and chemical bath deposition. The seed layer strategy was used to assist
      the growth of Bi2S3 nanorods for perfect interface contact between WO3 and Bi2S3.
      The as-prepared WO3/Bi2S3 composite exhibited a much enhanced photocurrent (5.95
      mA/cm2 at 0.9 V vs reversible hydrogen electrode), which is 35 and 1.4 times
      higher than those of pristine WO3 and WO3/Bi2S3 composite without a seed layer,
      respectively. In addition, higher incident photon-to-current conversion
      efficiency (68.8%) and photoconversion efficiency (1.70%) were achieved. The
      enhancement mechanism was investigated in detail, and the sufficient light
      absorption, efficient charge transport, and high carrier density simultaneously
      contribute to the improved PEC activity. These findings will open up new
      opportunities to develop other highly efficient heterostructures as
      photoelectrodes for PEC applications.

PMID- 29067800
TI  - Toward Artificial Mitochondrion: Mimicking Oxidative Phosphorylation in Polymer
      and Hybrid Membranes.
AB  - For energy supply to biomimetic constructs, a complex chemical energy-driven ATP
      generating artificial system was built. The system was assembled with bottom-up
      detergent-mediated reconstitution of an ATP synthase and a terminal oxidase into
      two types of novel nanocontainers, built from either graft copolymer membranes or
      from hybrid graft copolymer/lipid membranes. The versatility and biocompatibility
      of the proposed nanocontainers was demonstrated through convenient system
      assembly and through high retained activity of both membrane-embedded enzymes. In
      the future, the nanocontainers might be used as a platform for the functional
      reconstitution of other complex membrane proteins and could considerably expedite
      the design of nanoreactors, biosensors, and artificial organelles.

PMID- 29067801
TI  - Electrically Tunable Soft Photonic Gel Formed by Blue Phase Liquid Crystal for
      Switchable Color-Reflecting Mirror.
AB  - We report a robust soft photonic crystal system, fabricated using blue phase (BP)
      liquid crystal, which can efficiently filter the visible light. The BP gel system
      is obtained without surface treatment or polymerization, and thus is facile and
      cost effective to fabricate. Perfect monodomain with vivid color is achieved with
      a low electric field, which can be further tuned to reflect a second color. Most
      importantly, apart from the field-induced color switching, a dark/transparent
      state is also achieved due to complete unwinding of the BP helical structure. A
      potential application as a tunable color-reflecting mirror, which can be switched
      between "reflecting" and "transparent" states, is proposed.

PMID- 29067802
TI  - Ultrasensitive and Selective Organic FET-type Nonenzymatic Dopamine Sensor Based
      on Platinum Nanoparticles-Decorated Reduced Graphene Oxide.
AB  - Dopamine (DA), a catecholamine hormone, is an important neurotransmitter that
      controls renal and cardiovascular organizations and regulates physiological
      activities. Abnormal concentrations of DA cause unfavorable neuronal illnesses
      such as Parkinson's disease, schizophrenia, and attention deficit hyperactivity
      disorder/attention deficit disorder. However, the DA concentration is exceedingly
      low in patients and difficult to detect with existing biosensors. In this study,
      we developed an organic field-effect-transistor-type (OFET) nonenzyme biosensor
      using platinum nanoparticle-decorated reduced graphene oxide (Pt_rGO) for
      ultrasensitive and selective DA detection. The Pt_rGOs were fabricated by
      reducing GO aqueous solution-containing Pt precursors (PtCl4) with a chemical
      reducing agent. The Pt_rGOs were immobilized on a graphene substrate by pi-pi
      interactions and a conducting-polymer source-drain electrode was patterned on the
      substrate to form the DA sensor. The resulting OFET sensor showed a high
      sensitivity to remarkably low DA concentrations (100 * 10-18 M) and selectivity
      among interfering molecules. Good stability was expected for the OFET sensor
      because it was fabricated without an enzymatic receptor, and pi-pi conjugation is
      a part of the immobilization process. Furthermore, the OFET sensors are flexible
      and offer the possibility of wide application as wearable and portable sensors.

PMID- 29067803
TI  - Nylon Bristles and Elastomers Retain Centigram Levels of Triclosan and Other
      Chemicals from Toothpastes: Accumulation and Uncontrolled Release.
AB  - Triclosan (TCS), a broad-spectrum antimicrobial, is used in commercial
      toothpastes with reported dental benefits. Our studies on 22 popular manual
      toothbrushes in the U.S. showed that common toothbrush head components can
      accumulate substantial amounts of TCS after brushing with TCS-formulated
      toothpastes (TCS-TPs). After simulated 3-month brushing with a commercial best
      selling TCS-TP, over one third of the adults' toothbrushes showed a cumulative
      TCS uptake of 21-37.5 mg, equivalent to 7-12.5 doses of the TCS used per
      brushing. Similar results were observed on children's toothbrushes with small pea
      size heads. Elastomer components were found to be the main contributor while both
      nylon bristles and elastomers could act as absorptive sinks for TCS during
      brushing. Studies on six different TCS-TPs containing 0.3 wt% TCS showed similar
      profiles of TCS accumulation. The absorbed TCS was gradually released into
      toothpaste slurries after switching to TCS-free alternatives. Release of TCS,
      which typically measured at a fraction (<75%) of the standard dose using the TCS
      TPs, continued for over 2 weeks and occurred most rapidly in peroxide-containing
      "whitening" toothpastes, followed by alkaline and surfactant-rich toothpastes.
      The accumulating effect was not exclusive to TCS but was commonly observed on
      several chemicals identified in TCS-TPs and a range of regular toothpastes.

PMID- 29067804
TI  - Bioinspired Design of Underwater Superaerophobic and Superaerophilic Surfaces by
      Femtosecond Laser Ablation for Anti- or Capturing Bubbles.
AB  - A micro-/nanoscale hierarchical rough structure inspired by the underwater
      superaerophobicity of fish scales was fabricated by ablation of a silicon surface
      by a femtosecond laser. The resultant silicon surface showed superhydrophilicity
      in air and became superaerophobic after immersion in water. Additionally,
      inspired by the underwater superaerophilicity of lotus leaves, we showed that the
      polydimethylsiloxane surface after femtosecond laser ablation exhibits
      superhydrophobicity in air and becomes superaerophilic in water. The underwater
      superaerophobic surface showed excellent antibubble ability, whereas the
      underwater superaerophilic surface could absorb and capture air bubbles in a
      water medium. The experimental results revealed that the in-air superhydrophilic
      surface generally shows superaerophobicity in water and that the in-air
      superhydrophobic surface generally shows underwater superaerophilicity. An
      underwater superaerophobic porous aluminum sheet with through microholes was
      prepared, and this sheet was able to intercept underwater bubbles and further
      remove bubbles from water. In contrast, the underwater superaerophilic porous
      polytetrafluoroethylene sheet could allow the bubbles to pass through the sheet.
      We believe that these results are highly significant for providing guidance to
      researchers and engineers for obtaining excellent control of bubbles' behavior on
      a solid surface in a water medium.

PMID- 29067805
TI  - Gentle Introduction to the Statistical Foundations of False Discovery Rate in
      Quantitative Proteomics.
AB  - The vocabulary of theoretical statistics can be difficult to embrace from the
      viewpoint of computational proteomics research, even though the notions it
      conveys are essential to publication guidelines. For example, "adjusted p
      values", "q-values", and "false discovery rates" are essentially similar
      concepts, whereas "false discovery rate" and "false discovery proportion" must
      not be confused, even though "rate" and "proportion" are related in everyday
      language. In the interdisciplinary context of proteomics, such subtleties may
      cause misunderstandings. This article aims to provide an easy-to-understand
      explanation of these four notions (and a few other related ones). Their
      statistical foundations are dealt with from a perspective that largely relies on
      intuition, addressing mainly protein quantification but also, to some extent,
      peptide identification. In addition, a clear distinction is made between concepts
      that define an individual property (i.e., related to a peptide or a protein) and
      those that define a set property (i.e., related to a list of peptides or
      proteins).

PMID- 29067806
TI  - Photo-oxidation of Dimethyl Malonate Initiated by Chlorine Atoms in Gas Phase:
      Kinetics and Mechanism.
AB  - The rate coefficient for the gas-phase reaction of chlorine atoms with dimethyl
      malonate (DMM, CH3OC(O)CH2C(O)OCH3) was determined at 298 K using relative
      methods giving a value of (3.8 +/- 0.4) * 10-12, cm3 molecule-1 s-1). The photo
      oxidation mechanism of DMM was also investigated. The main products were
      identified by infrared spectroscopy, and computational calculations were
      performed in order to support the experimental data. The results reveal that the
      photo-oxidation occurs mainly by the abstraction of an H atom from the methyl
      groups. The CH3OC(O)CH2C(O)OCH2O* radical formed subsequently reacts according to
      three competitive paths: reaction with molecular oxygen to yield
      CH3OC(O)CH2C(O)OC(O)H, isomerization-unimolecular decomposition to lead finally
      to CH3OC(O)C(O)H, CO2, and HC(O)OH, and alpha-ester rearrangement to form
      monomethyl malonate and carbon monoxide. The yield of products as a function of
      oxygen pressure was also determined.

PMID- 29067807
TI  - Unravelling Contaminants in the Anthropocene Using Statistical Analysis of Liquid
      Chromatography-High-Resolution Mass Spectrometry Nontarget Screening Data
      Recorded in Lake Sediments.
AB  - The significant increase in traces of human activity in the environment worldwide
      provides evidence of the beginning of a new geological era, informally named the
      Anthropocene. The rate and variability of these human modifications at the local
      and global scale remain largely unknown, but new analytical methods such as high
      resolution mass spectrometry (HRMS) can help to characterize chemical
      contamination. We therefore applied HRMS to investigate the contamination history
      of two lakes in Central Europe over the preceding 100 years. A hierarchical
      clustering analysis (HCA) of the collected time series data revealed more than 13
      000 profiles of anthropogenic origin in both lakes, defining the beginning of
      large-scale human impacts during the 1950s. Our results show that the analysis of
      temporal patterns of nontarget contaminants is an effective method for
      characterizing the contamination pattern in the Anthropocene and an important
      step in prioritizing the identification of organic contaminants not yet
      successfully targeted by environmental regulation and pollution reduction
      initiatives. As proof of the concept, the success of the method was demonstrated
      with the identification of the pesticide imazalil, which probably originated from
      imported fruits. This new approach applicable to palaeoarchives can effectively
      be used to document the time and rate of change in contamination over time and
      provide additional information on the onset of the Anthropocene.

PMID- 29067808
TI  - Three-Dimensional Flexible All-Organic Conductors for Multifunctional Wearable
      Applications.
AB  - Wearable textile electrodes based on pi-conjugated polymers are appealing
      alternatives to carbon fabrics, conductive yarns, or metal wires because of their
      design flexibility, low cost, flexibility, and high throughput. This provides the
      benefits of both electronics and textiles. Herein, a general and new method has
      been developed to produce tailorable, wearable energy devices that are based on
      three-dimensional (3D) poly(3,4-ethylenedioxythiophene) (PEDOT)-coated textile
      conductors. To obtain the desired electrode materials, both facile solution
      dropping polymerization methods are used to fabricate a 3D flexible PEDOT
      conductor on a cotton textile (PEDOT/textile). PEDOT/textile shows a very low
      sheet resistance of 4.6-4.9 Omega.sq-1. Here, we employ the example of this 3D
      network-like structure and the excellent electrical conductivities under the
      large deformation of PEDOT/textiles to show that wearable and portable heaters
      have immense potential. A flexible textile heater with a large area (8 * 7.8 cm2)
      reached a saturation temperature of ~83.9  degrees C when a bias of 7 V was
      applied for ~70 s due to the good electrical conductivity of PEDOT. To
      demonstrate the performance of all-solid-state supercapacitors, nano-ascidian
      like PEDOT (PEDOT-NA) arrays were prepared via a simple vapor-phase
      polymerization of 3,4-ethylenedioxythiophene on PEDOT/textile to increase both
      the surface area and the number of ion diffusion paths. The PEDOT-NA arrays on
      PEDOT/textile showed outstanding performance with an areal capacitance of 563.3
      mF.cm-2 at 0.4 mA.cm-2 and extraordinary mechanical flexibility. The maximum
      volumetric power density and energy density of the nanostructured PEDOT on the
      textile were 1.75 W.cm-3 and 0.0812 Wh.cm-3, respectively. It is expected that
      the wearable nanostructured conducting polymers will have advantages when used as
      structures for smart textronics and energy conversion/storage.

PMID- 29067809
TI  - Combined in Vivo Amperometric Oximetry and Electrophysiology in a Single Sensor:
      A Tool for Epilepsy Research.
AB  - Seizures are paroxysmal events in which increased neuronal activity is
      accompanied by an increase in localized energetic demand. The ability to
      simultaneously record electrical and chemical events using a single sensor poses
      a promising approach to identify seizure onset zones in the brain. In the present
      work, we used ceramic-based platinum microelectrode arrays (MEAs) to perform high
      frequency amperometric recording of local pO2 and local field potential (LFP)
      related currents during seizures in the hippocampus of chronically implanted
      freely moving rats. Resting levels of O2 in the rodent brain varied between 6.6
      +/- 0.7 MUM in the dentate gyrus (DG) region of the hippocampus and 22.1 +/- 4.9
      MUM in the cerebral cortex. We also observed an expected increase in hippocampal
      pO2 (15 +/- 4% from baseline) in response to tail pinch stress paradigm. Finally,
      induction of status epilepticus by intrahippocampal injection of pilocarpine
      induced biphasic changes in pO2 in the hippocampus. The initial dip at seizure
      onset (DeltaO2 = -4.5 +/- 0.7 MUM) was followed by a prolonged hyperoxygenation
      phase (DeltaO2 = +10.4 +/- 2.9 MUM). By acquiring the amperometry signal with a
      high sampling rate of 100 Hz we decomposed the raw signal in an oximetry
      recording (<1 Hz) and LFP recording (>1 Hz), demonstrating that each individual
      Pt site can simultaneously report changes in local pO2 and LFP-related currents
      during pilocarpine-induced seizure activity. This has high potential for
      translation into the clinical setting supported on intracranial grid or strip
      electrodes.

PMID- 29067810
TI  - A Solid-State Intrinsically Stretchable Polymer Solar Cell.
AB  - An organic solar cell based on a bulk heterojunction of a conjugated polymer and
      a methanofullerene PC61BM or PC71BM exhibits a complex morphology that controls
      both its photovoltaic and mechanical compliance (flexibility and stretchability).
      Here, the donor-acceptor blend of poly(thieno[3,4-b]-thiophene/benzodithiophene)
      (PTB7) and PC71BM containing a small amount of diiodooctane (DIO) in the spin
      casting solution is reported to exhibit elastic deformability. The blend
      comprises nanometer-size, nanocrystalline grains that are relatively uniformly
      distributed. Large external deformation is accommodated by relative sliding
      between the grains. Reorientation of the nanocrystallites and the global
      reorientation of the PTB7 polymer chain were observed along the stretching
      direction up to 100% strain, which was reversible as the blend was allowed to
      relax to 0% strain. The polymer solar cell based on PTB7:PC71BM:DIO with such
      reversible morphological changes exhibited a rubbery elasticity at room
      temperature. The device could be stretched up to 100% strain, and the power
      conversion efficiency shows a slight increase up to 30% strain and a global
      increase of power generation as the photoactive area increases with strain. Solar
      cells were fabricated employing a layer of the PTB7:PC71BM:DIO blend sandwiched
      between a pair of stretchable transparent electrodes, each comprising a stack of
      a silver nanowire percolation network and a single-wall carbon nanotube network
      embedded in the surface of a poly(urethane acylate) elastomer film. The solar
      cells were semitransparent and could be stretched like a rubbery film by as much
      as 100% strain. The measured power-conversion efficiency was 3.48%, which was
      increased to 3.67% after one cycle of stretching to 50% strain and lowered to
      2.99% after 100 stretching cycles. The total power generation from the cells was
      significantly increased, thanks to the expanded active area as the cells were
      stretched.

PMID- 29067811
TI  - Critical Surface Parameters for the Oxidative Coupling of Methane over the Mn-Na
      W/SiO2 Catalyst.
AB  - The work here presents a thorough evaluation of the effect of Mn-Na-W/SiO2
      catalyst surface parameters on its performance in the oxidative coupling of
      methane (OCM). To do so, we used microporous dealuminated beta-zeolite (Zeo), or
      mesoporous SBA-15 (SBA), or macroporous fumed silica (Fum) as precursors for
      catalyst preparation, together with Mn nitrate, Mn acetate and Na2WO4.
      Characterizing the catalysts by inductively coupled plasma-optical emission
      spectroscopy, N2 physisorption, X-ray diffraction, high-resolution scanning
      electron microscopy-energy-dispersive spectroscopy, X-ray photoelectron
      spectroscopy, and catalytic testing enabled us to identify critical surface
      parameters that govern the activity and C2 selectivity of the Mn-Na-W/SiO2
      catalyst. Although the current paradigm views the phase transition of silica to
      alpha-cristobalite as the critical step in obtaining dispersed and stable metal
      sites, we show that the choice of precursors is equally or even more important
      with respect to tailoring the right surface properties. Specifically, the SBA
      based catalyst, characterized by relatively closed surface porosity, demonstrated
      low activity and low C2 selectivity. By contrast, for the same composition, the
      Zeo-based catalyst showed an open surface pore structure, which translated up to
      fourfold higher activity and enhanced selectivity. By varying the overall
      composition of the Zeo catalysts, we show that reducing the overall W
      concentration reduces the size of the Na2WO4 species and increases the catalytic
      activity linearly as much as fivefold higher than the SBA catalyst. This linear
      dependence correlates well to the number of interfaces between the Na2WO4 and
      Mn2O3 species. Our results combined with prior studies lead us to single out the
      interface between Na2WO4 and Mn2O3 as the most probable active site for OCM using
      this catalyst. Synergistic interactions between the various precursors used and
      the phase transition are discussed in detail, and the conclusions are correlated
      to surface properties and catalysis.

PMID- 29067812
TI  - Structurally Analogous Degradable Version of Fluorene-Bipyridine Copolymer with
      Exceptional Selectivity for Large-Diameter Semiconducting Carbon Nanotubes.
AB  - Separation of electronically pure, narrowly dispersed, pristine, semiconducting
      single-walled carbon nanotubes (CNTs) from a heterogeneous as-synthesized mixture
      is essential for various semiconducting technologies and biomedical applications.
      Although conjugated polymer wrappers are often utilized to facilitate electronic
      type sorting, it is highly desirable to remove organic residues from the
      resulting devices. We report here the design and synthesis of a mild acid
      degradable pi-conjugated polyimine polymer, poly[(9,9-di-n-octyl-2,7-fluoren
      dinitrilomethine)-alt-co-(6,6'-{2,2'-bipyridyl-dimethine})] (PFO-N-BPy), that is
      structurally analogous to the commonly used and commercially available poly[(9,9
      dioctylfluorenyl-2,7-diyl)-alt-co-(6,6'-(2,2'-bipyridine))] (PFO-BPy). An acid
      cleavable imine link (-HC?N-) was introduced in the PFO-N-BPy backbone to impart
      degradability, which is absent in PFO-BPy. PFO-N-BPy was synthesized via a metal
      catalyst-free aza-Wittig reaction in high yields. PFO-N-BPy with a degree of
      polymerization of just ~10 showed excellent (>99% electronic purity) selectivity
      for both large-diameter (1.3-1.7 nm) arc-discharge semiconducting CNTs (S-CNTs)
      and smaller diameter (0.8-1.2 nm) high-pressure carbon monoxide
      disproportionation reaction S-CNTs. Overall, the selectivity for the
      semiconducting species is similar to that of PFO-BPy but with an advantage of
      complete depolymerization under mild acidic conditions into recyclable monomers.
      We further show by ultraviolet-visible spectroscopy, X-ray photoelectron
      spectroscopy, and scanning electron microscopy that the PFO-N-BPy-wrapped S-CNTs
      can be aligned into a monolayer array on gate dielectrics using a floating
      evaporative self-assembly process from which the polymer can be completely
      removed. Short channel field effect transistors were fabricated from the polymer
      stripped aligned S-CNT arrays, which further confirmed the semiconducting purity
      on the order of 99.9% or higher.

PMID- 29067813
TI  - Gas-Permeable Membrane-Based Conductivity Probe Capable of In Situ Real-Time
      Monitoring of Ammonia in Aquatic Environments.
AB  - Aquatic ammonia has toxic effects on aquatic life. This work reports a gas
      permeable membrane-based conductivity probe (GPMCP) developed for real-time
      monitoring of ammonia in aquatic environments. The GPMCP innovatively combines a
      gas-permeable membrane with a boric acid receiving phase to selectively extract
      ammonia from samples and form ammonium at the inner membrane interface. The rate
      of the receiving phase conductivity increase is directly proportional to the
      instantaneous ammonia concentration in the sample, which can be rapidly and
      sensitively determined by the embedded conductivity detector. A precalibration
      strategy was developed to eliminate the need for an ongoing calibration. The
      analytical principle and GPMCP performance were systematically validated. The
      laboratory results showed that ammonia concentrations ranging from 2 to 50 000
      MUg L-1 can be detected. The field deployment results demonstrated the GPMCP's
      ability to obtain high-resolution continuous ammonia concentration profiles and
      the absolute average ammonia concentration over a prolonged deployment period. By
      inputting the temperature and pH data, the ammonium concentration can be
      simultaneously derived from the corresponding ammonia concentration. The GPMCP
      embeds a sophisticated analytical principle with the inherent advantages of high
      selectivity, sensitivity, and accuracy, and it can be used as an effective tool
      for long-term, large-scale, aquatic-environment assessments.

PMID- 29067814
TI  - Effectiveness of Commercial and Homemade Washing Agents in Removing Pesticide
      Residues on and in Apples.
AB  - Removal of pesticide residues from fresh produce is important to reduce pesticide
      exposure to humans. This study investigated the effectiveness of commercial and
      homemade washing agents in the removal of surface and internalized pesticide
      residues from apples. Surface-enhanced Raman scattering (SERS) mapping and liquid
      chromatography tandem mass spectrometry (LC-MS/MS) methods were used to determine
      the effectiveness of different washing agents in removing pesticide residues.
      Surface pesticide residues were most effectively removed by sodium bicarbonate
      (baking soda, NaHCO3) solution when compared to either tap water or Clorox
      bleach. Using a 10 mg/mL NaHCO3 washing solution, it took 12 and 15 min to
      completely remove thiabendazole or phosmet surface residues, respectively,
      following a 24 h exposure to these pesticides, which were applied at a
      concentration of 125 ng/cm2. LC-MS/MS results showed, however, that 20% of
      applied thiabendazole and 4.4% of applied phosmet had penetrated into the apples
      following the 24 h exposure. Thiabendazole, a systemic pesticide, penetrated 4
      fold deeper into the apple peel than did phosmet, a non-systemic pesticide, which
      led to more thiabendazole residues inside the apples, which could not be washed
      away using the NaHCO3 washing solution. This study gives us the information that
      the standard postharvest washing method using Clorox bleach solution for 2 min is
      not an effective means to completely remove pesticide residues on the surface of
      apples. The NaHCO3 method is more effective in removing surface pesticide
      residues on apples. In the presence of NaHCO3, thiabendazole and phosmet can
      degrade, which assists the physical removal force of washing. However, the NaHCO3
      method was not completely effective in removing residues that have penetrated
      into the apple peel. The overall effectiveness of the method to remove all
      pesticide residues diminished as pesticides penetrated deeper into the fruit. In
      practical application, washing apples with NaHCO3 solution can reduce pesticides
      mostly from the surface. Peeling is more effective to remove the penetrated
      pesticides; however, bioactive compounds in the peels will become lost too.

PMID- 29067815
TI  - Diagnostic performance of advanced modeled iterative reconstruction applied
      images for detecting urinary stones on submillisievert low-dose computed
      tomography.
AB  - Background Repeated computed tomography (CT) scans may be an issue in young
      adults with urinary stones. Therefore, it is important to know how far the dose
      can be reduced while maintaining the diagnostic performance. Purpose To generate
      a hypothesis that it is feasible to decrease the radiation dose to a sub
      millisievert (mSv) level with the addition of advanced modeled iterative
      reconstruction (ADMIRE) while maintaining the sensitivity to standard-dose CT
      (SDCT) for the detection of urinary stones. Material and Methods Ninety-two
      consecutive patients with urinary stones underwent non-enhanced CT that consisted
      of standard (120 kVp, 200 mAs) and lose-dose (LDCT) (80 kVp, 60 mAs). The LDCT
      images were reconstructed separately with five different strengths of ADMIRE
      (hereafter, S1-S5) and filtered back projection (FBP). Two blinded radiologists
      independently recorded a number of urinary stones in the six LDCT datasets and
      SDCT. The sensitivity of each set for detecting urinary stones was compared using
      the McNemar test. Results A total of 240 urinary stones were analyzed. The
      sensitivities of the six LDCT datasets showed no difference (FBP, S1-S5, for
      reader 1: 78%, 79%, 79%, 80%, 80%, and 80%; for reader 2: 64%, 63%, 64%, 64%,
      65%, and 66%, P > 0.05, respectively), which were lower than those of SDCT for
      both readers (reader 1: 88%; reader 2: 81%, P < 0.0001, respectively). Conclusion
      Despite the addition of ADMIRE, it may not be feasible to decrease the radiation
      dose to a sub-mSv level while maintaining the sensitivity to SDCT for the
      detection of urinary stones.

PMID- 29067816
TI  - Sex and age differences in head acceleration during purposeful soccer heading.
AB  - Differences in head-neck segment mass, purposeful heading technique, and cervical
      strength and stiffness may contribute to differences in head accelerations across
      sex and age. The purpose of this study was to compare head acceleration across
      sex and age (youth [12-14 years old], high school and collegiate) during
      purposeful soccer heading. One-hundred soccer players (42 male, 58 female, 17.1
      +/- 3.5 years, 168.5 +/- 20.3 cm, 61.5 +/- 13.7 kg) completed 12 controlled
      soccer headers at an initial ball velocity of 11.2 m/s. Linear and rotational
      accelerations were measured using a triaxial accelerometer and gyroscope and were
      transformed to the head centre-of-mass. A MANOVA revealed a significant
      multivariate main effect for sex (Pillai's Trace = .165, F(2,91) = 11.868, p <
      .001), but not for age (Pillai's Trace = .033, F(4,182) = 0.646, p = .630). Peak
      linear and rotational accelerations were higher in females (40.9 +/- 13.3 g; 3279
      +/- 1065 rad/s2) than males (27.6 +/- 8.5 g, 2219 +/- 823 rad/s2). These data
      suggest that under controlled soccer heading conditions, females may be exposed
      to higher head accelerations than males.

PMID- 29067817
TI  - Effect of different ethanolic concentrations on antioxidant properties and
      cytoprotective activities of Platostoma palustre Blume.
AB  - The objective of this study was to evaluate the antioxidant activities of Mesona
      procumbens ethanolic extracts (MPEEs) which displayed variable antioxidant levels
      with different ethanolic concentrations. Compared to MPEEs with 20, 40 and 80%
      ethanol, the 60% MPEE exhibited a higher total phenol content (TPC), total
      flavonoid content (TFC), 1,1-diphenyl-2-picryl hydrazyl (DPPH)- and 2,2-azino-bis
      (3-ethyl benzothiazoline-6-sulphonic acid (ABTS)-scavenging activities, reducing
      power, protection of Raw 264.7 mouse macrophages against H2O2-induced damage, and
      inhibition of reactive oxygen species (ROS) induced by 2,2-azobis(2-amidino
      propane) dihidrochloride (AAPH). IC50 values of DPPH and ABTS radicals by MPEEs
      were highly and significantly associated with TPCs and TFCs. The most significant
      protective effect against oxidative DNA damage was also found to be the 60% MPEE
      at a concentration of 3.6 mg/mL. In addition, the cell viability test showed that
      none of the MPEEs had any cell toxicity up to a concentration of 250 MUg/mL. The
      60% MPEE exhibited higher in vitro and ex vivo antioxidant activities, possessed
      a protective capability for the biological membrane system, and can be used as a
      functional ingredient representing a potential source of natural antioxidants to
      prevent and treat oxidative stress-related disorders.

PMID- 29067818
TI  - Kinetics of the lower limb during two typical Tai Chi movements in the elderly.
AB  - Tai Chi (TC) is a recommended exercise for elderly people; however, its loading
      on the joints of the lower limbs is unknown. This study examined the 3D kinetics
      of the lower limbs during two typical TC movements and walking in the elderly.
      Fifteen experienced TC practitioners participated. Ground reaction forces, joint
      moments and time-to-peak joint moment generation were analysed. Compared with
      walking, both TC movements generated significantly (1) smaller peak ground
      reaction forces in all directions, except the anterior; (2) larger hip extension,
      adduction and internal rotational moments, knee adduction/abduction and internal
      rotation moments and eversion/inversion and external/internal moments of ankle
      foot; and (3) longer peak moment generation time for hip extension, adduction and
      internal rotation, knee extension and ankle dorsiflexion and inversion. The TC
      loading patterns are consistent with the mechanical behaviour of biological
      tissues, which could help to strengthen the lower extremities and prevent falls
      in the elderly.

PMID- 29067819
TI  - An Interactive Web-Based Intervention to Achieve Healthy Weight in Young
      Children.
AB  - This prospective, randomized, controlled trial for parents of overweight and
      obese 3- to 7-year-olds was performed to assess the feasibility of a program
      promoting healthy eating and lifestyle by targeting parents as agents of change.
      The intervention was composed of 6-in-person group sessions and a customized
      website over 12 months. The control group received customary care. The primary
      outcome was feasibility of the intervention to promote healthy behavior change
      measured by attendance. The secondary outcome was effectiveness assessed by
      attaining reduced body mass index (BMI) z scores, healthy behavior changes and
      increased parent self-efficacy. Seventy-three child-parent dyads were enrolled;
      14 parents never attended any sessions. Participation in follow-up assessments
      did not meet the hypothesized level. Ultimate BMI z scores did not differ between
      control and intervention groups. Parenting skills did not improve in the
      intervention group. This intervention to achieve healthy lifestyle changes in
      children via their parents as "change agents" was unsuccessful.

PMID- 29067821
TI  - Intractable Right-Sided Abdominal Pain in a Female, Adolescent Softball Player.

PMID- 29067820
TI  - ' ... But i'm still tired': the experience of fatigue among South African
      adolescents receiving antiretroviral therapy.
AB  - In adults with HIV, fatigue is a common and disabling symptom associated with
      suboptimal adherence to antiretroviral therapy (ART), poor health and well-being,
      reduced economic productivity, and increased health care resource use. Fatigue
      among adolescents with HIV is relatively unexplored. We recruited 14 adolescents
      with HIV receiving ART in South Africa whom we interviewed about fatigue. We used
      thematic analysis to analyse the data. Participants reported difficulties in
      maintaining concentration at school and resorting to self-care strategies such as
      napping during school hours. Adolescents also described actively avoiding
      activities thought to lead to fatigue and spoke of being socially excluded by
      their peers. The findings demonstrate that adolescents experienced symptoms
      consistent with a definition of fatigue, which had implications for their
      academic and social lives.

PMID- 29067822
TI  - Novel lipoxygenase inhibitor, 1-ethenoxy-2-methylbenzene, from marine
      cyanobacteria Microcoleus chthonoplastes.
AB  - Lipoxygenase (LOX) inhibitors are considered to be important anti-inflammatory
      agents as it can control many inflammatory responses to some extent. Even though
      the marine bio-systems are not well explored, they are considered to be one of
      the promising repositories for drug lead molecules against variety of diseases.
      In the present study a new LOX inhibitor compound, 1-ethenoxy-2-methylbenzene,
      reported first time from a living system, Microcoleus chthonoplastes, has been
      isolated by activity guided fractionation and further structurally characterised
      by techniques such as FTIR, NMR and LC MS/MS. Further enzyme kinetics, isothermal
      titration calorimetry and molecular docking methods were used in order to get a
      better understanding of enzyme-ligand interactions. This exploration suggests its
      worthiness as a lead molecule for the development of a better anti-inflammatory
      drug. Its high structure-activity resemblance to cuminaldehyde from cumin seeds,
      which is earlier reported as a LOX inhibitor, is also established.

PMID- 29067823
TI  - Viral Infection of the Central Nervous System: An Uncommon Etiology.

PMID- 29067824
TI  - Guilty Until Proven Innocent.

PMID- 29067825
TI  - Phacomatosis Pigmentovascularis: Simple Presentation of a Not So Simple
      Dermatological Condition.
AB  - Cutaneous vascular malformations are rare disorders that are often confused with
      more common infantile hemangiomas. We report the case of a female infant who
      presented with phacomatosis pigmentovascularis type IIA with features of Klippel
      Trenaunay-Weber syndrome.

PMID- 29067826
TI  - Yellow Nail Syndrome Presenting With a Pericardial Effusion: A Case Report and
      Review of the Literature.
AB  - Yellow nail syndrome (YNS) is a constellation of clinical findings including at
      least 2 of the 3 features of thickened yellow nails, respiratory tract
      involvement, and lymphedema. We report the case of a middle-aged man presenting
      with dystrophic, thickened yellow nails; an idiopathic pericardial effusion in
      the absence of pleural effusion(s); and unilateral apical bronchiectasis found on
      computed tomography of the chest. This represents a unique presentation of YNS as
      the first report of a patient with YNS and a pericardial effusion in the absence
      of pleural effusions and lymphedema and is the 11th case report of YNS with
      pericardial effusion.

PMID- 29067828
TI  - Late-Breaking Abstracts of the 2017 International Headache Congress.

PMID- 29067827
TI  - Characterization of key aroma compounds from different rose essential oils using
      gas chromatography-mass spectrometry, gas chromatography-olfactometry and partial
      least squares regression.
AB  - To characterise the key aroma compounds of rose essential oils, five samples
      (Rosa damascena essential oil, Rosa centifolia essential oil, Rosa alba essential
      oil, Rosa rugosa cv. 'Plena' essential oil, Rosa xanthina Lindl essential oil)
      were analysed by gas chromatography-olfactometry (GC-O), gas chromatography-mass
      spectrometry (GC-MS) and quantitative descriptive analysis (QDA). Thirty-nine
      aroma compounds were selected as key aroma compounds by GC-MS and GC-O. The aroma
      of rose essential oils was described by 10 sensory attributes such as honey,
      sweet, fermented, spicy, fruity, woody, floral, herbal, green and fresh. The
      partial least squares regression (PLSR) result showed the relationship between
      key aroma compound and characteristic aromas of rose essential oils. This paper
      provided a reference for the flavourists.

PMID- 29067830
TI  - A new insecticidal havanensin-type limonoid from the roots of Trichilia sinensis
      Bentv.
AB  - One new havanensin-type limonoid (1) named trisinlin A with two known compounds
      (4E,8E)-2-[2'-hydroxyhexadecanoyl amino]-4,8-octadecadiene-1,3-diol (2), 9
      octadecenoic acid-2',3'-dihydroxypropyl ester (3) were isolated from the roots of
      Trichilia sinensis. The structure of the new compound was unambiguously
      determined through comprehensive spectroscopic analyses including 1D and 2D NMR,
      and mass spectrometry, as well as by comparison with the literature. Trisinlin A
      showed significant insecticidal activity against newly hatched larvae of
      Spodoptera litura.

PMID- 29067831
TI  - Social and structural factors increase inconsistent condom use by sex workers'
      one-time and regular clients in Northern Uganda.
AB  - While sex workers (SWs) bear the brunt of the epidemic in Uganda, there remains a
      dearth of empirical research on the structural drivers of HIV prevention among
      SWs. This study examined the drivers of inconsistent condom use by one-time and
      regular clients of young women SWs in Gulu, Northern Uganda. Data were drawn from
      the Gulu Sexual Health Study, a cross-sectional study of young SWs, aged 14 years
      and older (2011-2012). SWs were recruited using peer/SW-led outreach, in
      partnership with The AIDS Support Organization and other CBOs. Multivariable
      logistic regression was used to examine the correlates of inconsistent condom use
      by one-time and regular clients. In total, 84.5% of the 381 SWs servicing regular
      clients and 76.8% of the 393 SWs servicing one-time clients reported inconsistent
      client condom use. In multivariable analysis, physical/sexual violence by clients
      (AOR = 5.39; 95%CI 3.05-9.49), low sexual control by workers (measured by the
      validated Pulweritz scale) (AOR = 2.86; 95%CI 1.47-5.58), alcohol/drug use while
      working (AOR = 1.98; 95%CI 1.17-3.35) and migration to Gulu for sex work (AOR =
      1.73; 95%CI 0.95-3.14) were positively correlated with inconsistent condom use by
      one-time clients. Correlates of inconsistent condom use by regular clients
      included: low sexual control by workers (AOR = 4.63; 95%CI 2.32-9.23);
      physical/sexual violence by clients (AOR = 3.48; 95%CI 1.85-6.53); police
      harassment (AOR = 2.57; 95%CI 1.17-5.65); and being a single mother (AOR = 2.07;
      95%CI 1.09-3.93). Structural and interpersonal factors strongly influence
      inconsistent condom use by clients, with violence by clients and police, low
      sexual control by workers, migration and single-parenthood all linked to non
      condom use. There is a need for peer-led structural interventions that improve
      access to occupational health and safety standards (e.g., violence prevention and
      alcohol/drug harm reduction policies/programming). Shifts away from the current
      punitive approaches towards SWs are integral to the success of such
      interventions, as they continue to undermine HIV prevention efforts.

PMID- 29067833
TI  - Nonepileptic Myoclonus Following Bupropion Overdose.

PMID- 29067832
TI  - Features of Simultaneous Scalp and Intracranial EEG That Predict Localization of
      Ictal Onset Zone.
AB  - OBJECTIVE: To assess the utility of simultaneous scalp EEG in patients with focal
      epilepsy undergoing intracranial EEG evaluation after a detailed presurgical
      testing, including an inpatient scalp video EEG evaluation. METHODS: Patients who
      underwent simultaneous scalp and intracranial EEG (SSIEEG) monitoring were
      classified into group 1 or 2 depending on whether the seizure onset zone was
      delineated or not. Seizures were analyzed using the following 3 EEG features at
      the onset of seizures latency, location, and pattern. RESULTS: The criteria
      showed at least one of the following features when comparing SSIEEG: prolonged
      latency, absence of anatomical congruence, lack of concordance of EEG pattern in
      11.11% (1/9) of the patients in group 1 and 75 % (3/4) of the patients in group
      2. These 3 features were not present in any of the 5 patients who had Engel class
      I outcome compared with 1 of the 2 patients (50%) who had seizure recurrence
      after resective surgery. The mean latency of seizure onset in scalp EEG compared
      with intracranial EEG of patients in group 1 was 17.48 seconds (SD = 16.07)
      compared with 4.33 seconds (SD = 11.24) in group 2 ( P = .03). None of the
      seizures recorded in patients in group 1 had a discordant EEG pattern in SSIEEG.
      CONCLUSION: Concordance in EEG features like latency, location, and EEG pattern,
      at the onset of seizures in SSIEEG is associated with a favorable outcome after
      epilepsy surgery in patients with intractable focal epilepsy. SIGNIFICANCE:
      Simultaneous scalp EEG complements intracranial EEG evaluation even after a
      detailed inpatient scalp video EEG evaluation and could be part of standard
      intracranial EEG studies in patients with intractable focal epilepsy.

PMID- 29067834
TI  - Mindfulness instruction for HIV-infected youth: a randomized controlled trial.
AB  - HIV-infected youth experience many stressors, including stress related to their
      illness, which can negatively impact their mental and physical health. Therefore,
      there is a significant need to identify potentially effective interventions to
      improve stress management, coping, and self-regulation. The object of the study
      was to assess the effect of a mindfulness-based stress reduction (MBSR) program
      compared to an active control group on psychological symptoms and HIV disease
      management in youth utilizing a randomized controlled trial. Seventy-two HIV
      infected adolescents, ages 14-22 (mean age 18.71 years), were enrolled from two
      urban clinics and randomized to MBSR or an active control. Data were collected on
      mindfulness, stress, self-regulation, psychological symptoms, medication
      adherence, and cognitive flexibility at baseline, post-program, and 3-month
      follow-up. CD4+ T lymphocyte and HIV viral load (HIV VL) counts were also pulled
      from medical records. HIV-infected youth in the MBSR group reported higher levels
      of mindfulness (P = .03), problem-solving coping (P = .03), and life satisfaction
      (P = .047), and lower aggression (P = .002) than those in the control group at
      the 3-month follow-up. At post-program, MBSR participants had higher cognitive
      accuracy when faced with negative emotion stimuli (P = .02). Also, those in the
      MBSR study arm were more likely to have or maintain reductions in HIV VL at 3
      month follow-up than those in the control group (P = .04). In our sample, MBSR
      instruction proved beneficial for important psychological and HIV-disease
      outcomes, even when compared with an active control condition. Lower HIV VL
      levels suggest improved HIV disease control, possibly due to higher levels of HIV
      medication adherence, which is of great significance in both HIV treatment and
      prevention. Additional research is needed to explore further the role of MBSR for
      improving the psychological and physical health of HIV-positive youth.

PMID- 29067835
TI  - Unguiculins A-C: cytotoxic bis-guanidine alkaloids from the French Polynesian
      sponge, Monanchora n. sp.
AB  - Two new acyclic bis-guanidine alkaloids, unguiculins B-C (2-3), were isolated
      from a French Polynesian sponge Monanchora n. sp. together with the known
      compound unguiculin A (1). Their structures were established by spectroscopic
      data interpretation and comparison with the literature. Unguiculins A-C displayed
      antiproliferative and cytotoxic efficacy against several human cancer cells with
      IC50 values in the micromolar range.

PMID- 29067836
TI  - Quality of life in patients with implantable cardioverter-defibrillator:
      systematic review of randomized controlled trials.
AB  - BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy significantly
      improves the survival of patients who are at high risk for sudden cardiac death.
      However, it is unclear whether this survival is accompanied by impairment on
      quality of life (QoL). OBJECTIVES: This systematic review sought to describe
      whether ICD therapy, as compared with standard treatment, can have an impact on
      QoL outcomes. METHODS: Extensive literature searches were carried out in PubMed,
      EMBASE, LILACS and Cochrane Library. Eligible studies were randomized controlled
      trials (RCTs) of ICD versus medical therapy that reported valid and reliable
      measures of QoL. Included studies were reviewed to determine baseline patient
      characteristics, mean duration of follow-up, questionnaires used to assess QoL
      and association between QoL scores and ICD shock therapy. RESULTS: Seven studies,
      enrolling a total of 5,701 patients, were included in this review. The analyzed
      trials showed conflicting results about the impact of ICD on QoL outcomes. Among
      the secondary prevention studies, CIDS reported a clear benefit from ICD and AVID
      showed no difference between ICD and amiodarone groups. Of the primary prevention
      trials, AMIOVIRT, MADIT II, DEFINITE, and SCD-HeFT found no evidence of impaired
      QoL in patients with an ICD. Evidence for an association between ICD shocks and
      QoL was mixed and seemed to depend on the interval between shocks and QoL
      assessment. CONCLUSION: There was no evidence of impaired QoL in patients with an
      ICD. However, ICD patients must be educated of all possible risks and benefits,
      including transitory declines in QoL after ICD shocks.

PMID- 29067837
TI  - Shared decision-making for psychiatric medication: A mixed-methods evaluation of
      a UK training programme for service users and clinicians.
AB  - BACKGROUND: Shared decision making (SDM) is recognised as a promising strategy to
      enhance good collaboration between clinicians and service users, yet it is not
      practised regularly in mental health. AIMS: Develop and evaluate a novel training
      programme to enhance SDM in psychiatric medication management for service users,
      psychiatrists and care co-ordinators. METHODS: The training programme design was
      informed by existing literature and local stakeholders consultations. Parallel
      group-based training programmes on SDM process were delivered to community mental
      health service users and providers. Evaluation consisted of quantitative measures
      at baseline and 12-month follow-up, post-programme participant feedback and
      qualitative interviews. RESULTS: Training was provided to 47 service users, 35
      care-coordinators and 12 psychiatrists. Participant feedback was generally
      positive. Statistically significant changes in service users' decisional conflict
      and perceptions of practitioners' interactional style in promoting SDM occurred
      at the follow-up. Qualitative data suggested positive impacts on service users'
      and care co-ordinators confidence to explore medication experience, and group
      based training was valued. CONCLUSIONS: The programme was generally acceptable to
      service users and practitioners. This indicates the value of conducting a larger
      study and exploring application for non-medical decisions.

PMID- 29067838
TI  - Stigmatization towards the mentally ill: Perceptions of psychiatrists, pre
      clinical and post-clinical rotation medical students.
AB  - BACKGROUND: Stigma towards the mentally ill is a well-known phenomenon and it is
      not restricted to certain communities or countries. Stigma, be it self-stigma or
      public stigma, has a major influence in mental health care. AIM: The aim of this
      study was to determine whether stigmatizing attitudes towards the mentally ill
      differ according to the level of knowledge about psychiatric illnesses and
      whether the level of exposure towards the mentally ill plays a role in
      stigmatizing attitudes. METHOD: This study was carried out by assessing
      psychiatrists ( n = 68), pre-clinical ( n = 194) and post-clinical ( n = 354)
      medical students' attitudes towards the mentally ill using the Mental Illness:
      Clinicians' Attitudes (MICA) scale. The scale is scored on a Likert scale with
      higher scores indicating higher levels of stigmatization. RESULTS: Participants
      in the three groups had statistical significant different levels of stigma with a
      decline in scores as you are more exposed to psychiatry. Familiarity with mental
      illness was associated with less stigma. Participants who had friends or family
      members who suffered from mental illness or they themselves suffered from a
      mental illness had less stigma. CONCLUSION: More exposure to mental health
      related issues are needed not only in communities but also in medical schools.
      Medical students need to be targeted for educational intervention because they
      are the future doctors who might pursue psychiatry as their field of choice.
      Stigma against psychiatry as a medical profession should also be addressed. If
      psychiatry is to be respected as a medical profession, mental illness-related
      stigma interventions need to be put in place to raise awareness about the
      negative impact of stigma.

PMID- 29067839
TI  - Social inclusion and relationship satisfaction of patients with a severe mental
      illness.
AB  - BACKGROUND: Research suggests that patients with a severe mental illness (SMI)
      are among the most social excluded in society. However, comparisons of social
      network composition and relationship satisfaction between SMI patients and a
      control group are rare. AIMS: Our aim was to compare differences in size,
      satisfaction and composition of the social network between patients with SMI and
      a control group. Potential sociodemographic and clinical risk factors in relation
      to social network size in SMI patients were explored. METHODS: The sample
      consisted of a control group ( N = 949) and SMI patients ( N = 211) who were
      under treatment in Dutch mental health care institutions. In these groups,
      network size, relationship satisfaction, sociodemographic and clinical (patients
      only) characteristics were assessed. RESULTS: Social network size was 2.5 times
      lower in SMI patients, which was also reflected in a lower relationship
      satisfaction. The composition of the social network of SMI patients differs from
      that of controls: patients' network seems to consist of a smaller part of
      friends. Different risk factors were associated with the impoverishment of the
      social network of family, friends and acquaintances of patients with SMI.
      CONCLUSION: SMI patients have very small networks compared to controls. This may
      be a problem, given the ongoing emphasis on outpatient treatment of SMI patients
      and self-dependence. This outcome advocates for more attention to social
      isolation of SMI patients and involvement of family in the treatment and
      aftercare of SMI patients.

PMID- 29067840
TI  - The relationships between problematic internet use, alexithymia levels and
      attachment characteristics in a sample of adolescents in a high school, Turkey.
AB  - The aim of this study is to investigate the relationships between attachment
      characteristics, alexithymia and problematic internet use (PIU) in adolescents.
      The study was performed on 444 high school students (66% female and 34% male).
      Internet Addiction Test (IAT), Toronto Alexithymia Scale (TAS-20) and Short Form
      of the Inventory of Parent and Peer Attachment (s-IPPA) scales were used. The
      adolescents who scored >=50 on IAT were considered as the PIU group and <50 were
      considered as control group. There was a moderate positive relationship between
      TAS-20 and IAT scores (r = .441), and a moderate negative relationship between
      TAS-20 and s-IPPA scores (r = -.392), and a negative weak relationship between
      IAT and s-IPPA scores (r = -.208). S-IPPA scores were significantly lower in the
      PIU group compared to the controls (p < .001). TAS-20 scores of the PIU group
      were significantly higher compared to the controls (p < .05). Logistic regression
      analysis indicated that s-IPPA scores and TAS-20 significantly predict the PIU
      development (p < .05). The results indicate that alexithymia increases the risk
      of PIU and higher attachment quality is a protective factor for both alexithymia
      and PIU. These results suggest that it is important to focus on the insecure
      attachment patterns and alexithymic characteristics when studying adolescents
      with PIU.

PMID- 29067841
TI  - Prevalence and correlates of metabolic syndrome in Hong Kong Chinese adults-a
      random community sample study.
AB  - The study investigates the prevalence and correlates of metabolic syndrome (MS)
      among Hong Kong Chinese adults. Random cluster sampling design and International
      Diabetes Federation (IDF) MS criteria were adopted. Totally 737 adults
      participated in questionnaire survey and received waist circumference (WC)
      measurement. Among them 335 showed central obesity (WC > 80 and 85 cm for women
      and men respectively). Subsequently 229 accepted blood test. Totally 71
      participants met MS criteria, suggesting an overall prevalence of 14.1%. Both
      central obesity and MS increase sharply with age. Chi-square/ANOVA analyses
      revealed significant positive associations between central obesity with: being
      male, marital status being married/cohabit, lower education level, occupation as
      managers or housewives, and alcohol consumption. For MS, the significant positive
      correlates were: lower education level, occupation as service workers or
      housewives, lower income level, and alcohol consumption. After controlling for
      age, binary logistic regression analyses suggested the significant risk factors
      for central obesity were being male (OR = 1.4), married/cohabit (OR = 1.8),
      longer working hours (OR = 1.5), eating less vegetables (OR = 1.5), and alcohol
      consumption (OR = 1.8). For MS, only alcohol consumption appeared to be a
      significant risk factor (OR = 2.3). Multivariate binary logistic regressions also
      supported that age group and alcohol consumption were significant predictors of
      MS. To conclude, adopting randomized cluster sampling and IDF criteria, the study
      revealed a prevalence rate of MS at 14.1%. Alcohol consumption appears to be the
      strongest risk factor of MS, which however needs further investigation.

PMID- 29067842
TI  - Shared Reading and Television Across the Perinatal Period in Low-SES Households.
AB  - The American Academy of Pediatrics recommends that shared reading commence as
      soon as possible after birth and screen-based media be discouraged for those less
      than 18 months old. Early routines can predict long-term use and health outcomes.
      This longitudinal study involved low-socioeconomic status mothers (n = 282)
      enrolled in home visiting. Surveys were administered prenatally and at 2 months
      old regarding shared reading and infant television viewing, and health literacy
      was screened prenatally. Planned age to initiate reading decreased from 2.8 to
      1.8 months old, 80% reading by 2 months old, averaging 1 to 3 days per week, with
      "too busy" being the major barrier. Planned age for infant TV decreased from 13.2
      to 4.3 months old, 68% viewing by 2 months old and more than half daily. TV was
      observed in 70% of infant sleep environments. Health literacy was correlated with
      perceived developmental benefits of shared reading (positively) and TV viewing
      (negatively), 43% of mothers scoring at risk for inadequate levels. A majority
      cited the prenatal period as opportune to discuss reading and TV.

PMID- 29067843
TI  - Fertility desires and preferences for safer conception strategies among people
      receiving care for HIV at a publicly-funded clinic in Seattle, WA.
AB  - Understanding fertility desires and preferences for HIV prevention among
      individuals living with HIV, including the potential use of pre-exposure
      prophylaxis (PrEP) by HIV uninfected partners, can inform the delivery of safer
      conception counseling to reduce the risk of HIV transmission during pregnancy
      attempts. Men and women, predominantly heterosexual, engaged in HIV care in
      Seattle, WA, self-administered a questionnaire and we abstracted antiretroviral
      therapy (ART) status and HIV viral levels from medical records. We summarized
      participants' sexual behavior, fertility desires, and preferences for safer
      conception strategies and used log-binomial regression to identify demographic,
      sexual, and behavioral factors associated with perceived acceptability of PrEP
      for HIV uninfected partners during pregnancy attempts. 52% of the 150
      participants were female and the mean age was 48 years (range 23-74). 94.7% of
      participants were using ART and 79.3% had HIV viral load < 40 copies/mL. 22.2% of
      men and 34.6% of women reported that a healthcare provider had initiated
      discussion about fertility desires. 28.7% of participants were reproductive-age
      and desired children. Among sexually active reproductive-age participants with
      fertility desires, 56.3% reported inconsistent condom use and 62.5% did not
      report using effective birth control. 74.4% of reproductive age participants with
      fertility desires perceived that PrEP would be acceptable to an HIV uninfected
      partner and there were no significant predictors of PrEP acceptability. Nearly
      one third of reproductive-aged individuals living with HIV expressed fertility
      desires, highlighting a need for safer conception counseling in this setting.
      PrEP and ART were favored safer conception strategies.

PMID- 29067844
TI  - Clinical feature and anti-phospholipid antibody profiles of pregnancy failure in
      young women with antiphospholipid antibody syndrome treated with conventional
      therapy.
AB  - OBJECTIVE: To elucidate clinical feature and anti-phospholipid antibody (aPL)
      profiles, including lupus anticoagulant (LA), anti-cardiolipin (CL) antibodies
      and anti-phosphatidylserine/prothrombin (PS/PT) antibodies, of pregnancy failure
      in patients with antiphospholipid antibody syndrome (APS) already treated with
      conventional therapy. MATERIALS AND METHODS: Thirty-four women with a history of
      pregnancy who were diagnosed with APS between 2008 and 2016 were included in the
      study. We defined the successful pregnancy group as women who gave birth to a
      healthy baby over 1500 g after 34 weeks of pregnancy under conventional treatment
      (heparin and/or low-dose aspirin). The unsuccessful pregnancy group was defined
      as women whose pregnancy outcomes did not meet the aforementioned criteria
      despite the conventional therapy. The clinical features and aPL profiles were
      compared between the two groups. RESULTS: Fifteen women were classified into the
      unsuccessful pregnancy group; seven women were in the successful pregnancy group.
      Having history of both thrombosis and pregnancy morbidity and LA positivity were
      significantly more prevalent in the unsuccessful pregnancy group than in the
      successful pregnancy group (p <.05, respectively). In contrast, single positivity
      of anti-CL antibody was negatively associated with APS-associated pregnancy
      morbidity under the conventional treatment (p <.01). The proportion of anti-PS/PT
      IgG-positive patients was significantly higher in the unsuccessful pregnancy
      group (p = .02, OR 18.7, 95% CI 1.50, 232.29) with high concordance rate with LA
      (97% consistence). CONCLUSION: History of both thrombosis and pregnancy morbidity
      and the positivity of LA and/or anti-PS/PT-IgG, not but anti-CL-antibodies were
      correlated with APS-associated pregnancy morbidity refractory to conventional
      treatment. Clinical feature and aPL profiles might help us to make risk
      assessment for adverse pregnancy outcomes in patients with APS.

PMID- 29067845
TI  - Serum interleukin-6 and survivin levels predict clinical response to etanercept
      treatment in patients with established rheumatoid arthritis: Methodological
      issues.

PMID- 29067847
TI  - Serum N-terminal proBNP, not troponin I, at presentation predicts long-term
      neurologic outcome in acute charcoal-burning carbon monoxide intoxication.
AB  - OBJECTIVE: This study aimed to investigate whether the serum N-terminal pro-brain
      natriuretic peptide (NT-proBNP) and troponin I levels at emergency department
      (ED) presentation predict long-term neurologic outcomes after acute charcoal
      burning carbon monoxide (CO) poisoning. METHODS: This retrospective study
      included 220 patients suffering from charcoal-burning CO poisoning. The
      demographics, serum NT-proBNP and troponin I levels at ED presentation,
      treatment, clinical course during hospitalization, and long-term neurologic
      outcomes were collected. RESULTS: The median serum NT-proBNP level at
      presentation was 48.8 (16.5-259) pg/mL, and 78 patients (35.5%) had elevated
      troponin I (>0.04 ng/mL) after acute charcoal-burning CO poisoning. The upper NT
      proBNP and elevated troponin I groups had higher prevalences of respiratory
      failure, hypotension, and myocardial injury during hospitalization and altered
      mentality (GCS <=14) at discharge than the lower NT-proBNP and normal troponin I
      groups. The incidence of persistent severe neurologic sequelae at 25 months after
      acute CO poisoning was 10.9%. The upper NT-proBNP and elevated troponin I groups
      had a higher incidence of poor long-term neurologic outcome than the counterpart
      groups. Log-transformed NT-proBNP and elevated troponin I were associated with
      poor long-term neurologic outcome in the univariate analysis, but only the
      adjusted log-transformed NT-proBNP remained an independent factor in the
      multivariate analysis. Compared with a predictive model including previously
      proposed predictors, the addition of log NT-proBNP improved the diagnostic
      accuracy for predicting poor long-term neurologic outcome. The serum NT-proBNP
      values for predicting poor long-term neurologic outcome were 74.6 and 32.7 pg/mL
      at fixed sensitivities of 95 and 99%, respectively. CONCLUSIONS: Elevated serum
      NT-proBNP at ED presentation is correlated with a risk of poor long-term
      neurologic outcome after discharge in cases of acute charcoal-burning CO
      poisoning. NT-proBNP could significantly improve the risk stratification of
      patients who will experience poor long-term neurologic outcome after CO
      poisoning. This potentially valuable marker should be further validated.

PMID- 29067846
TI  - Origins of fibroblasts in rheumatoid synovial tissues: Implications from organ
      fibrotic models.
AB  - Fibroblasts play crucial roles in the pathogenesis of rheumatoid arthritis (RA).
      Accumulation of fibroblasts in the synovial tissues characterizes the pathology
      of RA. Understanding how fibroblasts accumulate could lead to discovery of new
      therapeutic targets in RA treatment, while current antirheumatic therapies still
      have problems in efficacy and safety. In this regard, several studies have
      revealed cellular origins of fibroblasts in fibrotic tissues in murine models of
      organ fibrosis. Some studies employed lineage tracing, which bring generally
      convincing results, using transgenic mice. They demonstrated that resident
      fibroblasts, pericytes, mesenchymal stem cells, epithelial cells, endothelial
      cells and bone-marrow-derived and circulating cells can be cellular origins of
      fibroblasts in organ fibrotic tissues. In this review, we summarize and discuss
      available evidence for the origins of fibroblasts accumulating in the arthritic
      synovial tissues and organ fibrotic tissues.

PMID- 29067848
TI  - Distinct clinical correlates of immune thrombocytopenic purpura at diagnosis of
      childhood-onset and adult SLE.
AB  - OBJECTIVES: To compare clinical and laboratorial features between childhood-onset
      systemic lupus erythematosus (cSLE) and adult SLE (aSLE) at concomitant diagnosis
      of immune thrombocytopenic purpura (ITP). METHODS: This study evaluated 56 cSLE
      and 73 aSLE patients regularly followed at Pediatric and Rheumatology Divisions
      of the same University hospital with ITP (platelets count <100,000/mm3 in the
      absence of other causes) at lupus onset. RESULTS: Median current age was 11.6 and
      27.3 years in cSLE and aSLE, respectively. cSLE had a higher frequency of ITP
      compared to aSLE (17% vs. 4%, p < .0001) and the former group had more
      hemorrhagic manifestations (36% vs. 16%, p = .0143). Constitutional symptoms and
      reticuloendothelial manifestations (p < .05), as well as pericarditis (25% vs.
      10%, p = .029) and central nervous system (CNS) involvement (30% vs. 14%, p =
      .029) were more common in cSLE. Conversely, in aSLE, ITP was solely associated
      with cutaneous and articular involvements (p < .05). Concerning treatment,
      intravenous methylprednisolone, intravenous immunoglobulin, blood transfusion and
      platelets transfusion were more frequently used in the cSLE population (p < .05).
      CONCLUSION: ITP at cSLE has distinct features compared to aSLE with a more severe
      presentation characterized by concomitant constitutional/reticuloendothelial
      manifestations, CNS involvement and hemorrhagic manifestation. These findings
      reinforce the need for a more aggressive treatment in this age group.

PMID- 29067849
TI  - Investigation of dissolved cellulose in development of buccal discs for
      oromucosal drug delivery.
AB  - Mucoadhesive formulations have a wide scope of application for both systemic and
      local treatment of various diseases. In the case of recurrent aphthous
      stomatitis, to ensure effective therapy, the concentration of corticosteroids,
      and/or anesthetics at the mouth ulcer side should be maintained with minimal
      systemic absorption. Therefore, the aim of the study was to investigate cellulose
      based formulations, in achieving suitable hardness, mucoadhesiveness, and
      sustained release of the active ingredients directed towards the mucosa for an
      extended period of time (~4 h). This was examined by creating polymer reinforced
      cellulose composites which consisted of porous cellulose discs (CD) and different
      polymer components namely polyethylene glycol 6000 (PEG6000), polyethylene glycol
      400 (PEG400), and ethyl cellulose. Empty CDs were formed by dropping dissolved
      cellulose into coagulation medium. The empty porous CDs were immersed into
      different drug loading solutions which were prepared by dissolving three
      different concentrations of triamcinolone acetonide and lidocaine hydrochloride
      in five different ratios of PEG 6000:PEG 400:ethanol (w:w:w %) solutions. All
      formulations were investigated regarding drug content, release, hardness, and
      mucoadhesive properties. The results indicate that the non-dispersing buccal
      discs had sufficient hardness, drug content and in vitro release properties, but
      further studies are needed to achieve proper mucoadhesiveness.

PMID- 29067850
TI  - Prediction of cardiovascular events using risk scores or electrocardiogram: A
      farewell to arms.

PMID- 29067851
TI  - Can energy expenditure be accurately assessed using accelerometry-based wearable
      motion detectors for physical activity monitoring in post-stroke patients in the
      subacute phase?
AB  - Background In the subacute stroke phase, the monitoring of ambulatory activity
      and activities of daily life with wearable sensors may have relevant clinical
      applications. Do current commercially available wearable activity trackers allow
      us to objectively assess the energy expenditure of these activities? The
      objective of the present study was to compare the energy expenditure evaluated by
      indirect calorimetry during the course of a scenario consisting of everyday
      activities while estimating the energy expenditure using several commercialised
      wearable sensors in post-stroke patients (less than six months since stroke).
      Method Twenty-four patients (age 68.2 +/- 13.9; post-stroke delay 34 +/- 25 days)
      voluntarily participated in this study. Each patient underwent a scenario of
      various everyday tasks (transfer, walking, etc.). During the implementation,
      patients wore 14 wearable sensors (Armband, Actigraph GT3X, Actical, pedometer)
      to obtain an estimate of the energy expenditure. The actual energy expenditure
      was concurrently determined by indirect calorimetry. Results Except for the
      Armband worn on the non-plegic side, the results of our study show a significant
      difference between the energy expenditure values estimated by the various sensors
      and the actual energy expenditure when the scenario is considered as a whole.
      Conclusion The present results suggest that, for a series of everyday tasks, the
      wearable sensors underestimate the actual energy expenditure values in post
      stroke patients in the subacute phase and are therefore not accurate. Several
      factors are likely to confound the results: types of activity, prediction
      equations, the position of the sensor and the hemiplegia side.

PMID- 29067852
TI  - Seeking best practices for cardiac rehabilitation registries in Europe.

PMID- 29067854
TI  - Sex- and age-related differences in half-marathon performance and competitiveness
      in the world's largest half-marathon - the GoteborgsVarvet.
AB  - In road runners, the age-related performance decline has been well investigated
      for marathoners, but little is known for half-marathoners. We analysed data from
      138,616 runners (48,148 women and 90,469 men) competing between 2014 and 2016 in
      GoteborgsVarvet, the world's largest half-marathon. The men-to-women ratio in
      participants increased with age, the fastest race times were observed in age
      groups ?35 and 35-39 years in women and in age group 35-39 years in men, the main
      effect of sex and the sex * age group interaction on race time were trivial, and
      the competitiveness was denser in men and in the younger age groups. In summary,
      in half-marathon running in the largest half-marathon in the world, the
      GoteborgsVarvet, women achieved the fastest race time at an earlier age compared
      to men where the fastest race times were observed in women in age groups ?35 and
      35-39 years and in men in age group 35-39 years.

PMID- 29067853
TI  - Nordic walking for individuals with cardiovascular disease: A systematic review
      and meta-analysis of randomized controlled trials.
AB  - Background Exercise is the cornerstone of rehabilitation programmes for
      individuals with cardiovascular disease (IwCVD). Although conventional
      cardiovascular rehabilitation (CCVR) programmes have significant advantages, non
      conventional activities such as Nordic walking (NW) may offer additional health
      benefits. Our aim was to appraise research evidence on the effects of Nordic
      walking for individuals with cardiovascular disease. Design Systematic review and
      meta-analysis. Methods A literature search of clinical databases (PubMed,
      MEDLINE, Scopus, Web of Science, Cochrane) was conducted to identify any
      randomized controlled trials, including: (i) individuals with cardiovascular
      disease, (ii) analyses of the main outcomes arising from Nordic walking (NW)
      programmes. Data from the common outcomes were extracted and pooled in the meta
      analysis. Standardized mean differences (SMDs) were calculated and pooled by
      random effects models. Results Fifteen randomized controlled trials were included
      and eight trials entered this meta-analysis. Studies focused on coronary artery
      disease, peripheral arterial disease, heart failure and stroke. In coronary
      artery disease, significant differences between NW+CCVR and CCVR were found in
      exercise capacity (SMD: 0.49; p = 0.03) and dynamic balance (SMD: 0.55; p = 0.01)
      favouring NW+CCVR. In peripheral artery disease, larger changes in exercise
      duration (SMD: 0.93; p < 0.0001) and oxygen uptake (SMD: 0.64; p = 0.002) were
      observed following NW compared with controls. In heart failure, no significant
      differences were found between NW and CCVR or usual care for peak VO2 and
      functional mobility. In post-stroke survivors, functional mobility was
      significantly higher following treadmill programmes with poles rather than
      without (SMD: 0.80; p = 0.03). Conclusions These data portray NW as a feasible
      and promising activity for individuals with cardiovascular disease. Further
      studies are necessary to verify whether NW may be incorporated within CCVR for
      individuals with cardiovascular disease.

PMID- 29067855
TI  - Barriers and facilitators of access to HIV, harm reduction and sexual and
      reproductive health services by women who inject drugs: role of community-based
      outreach and drop-in centers.
AB  - There is limited data regarding women who inject drugs, and how harm-reduction
      services can be made more women-centered. This study explored experiences of
      Kenyan women who inject drugs, with regard to access to HIV, harm reduction and
      sexual and reproductive health (SRH) services. A total of 45 women who inject
      drugs and 5 key stakeholders participated in-depth interviews and focus group
      discussions. Thematic analysis of the data revealed that stigma, long distances,
      lack of confidentiality, user fees, multiple appointments, drug users'
      unfamiliarity with health facilities, disconnect in communication with healthcare
      providers, and healthcare providers' lack of understanding of women's needs were
      factors that impede women's access to health services. Community-based services,
      comprising of outreach and drop-in centers mitigate these barriers by building
      trust, educating women on their health and rights, linking women to health
      facilities, sensitizing health providers on the needs of women who inject drugs,
      and integrating women's SRH services into community-based harm-reduction
      outreach. Inclusion of SRH services into community-based harm-reduction
      activities increased women's interest and access to harm-reduction interventions.
      These findings underscore the need to strengthen community-based programming for
      women who inject drugs, and to integrate SRH services into needle and syringe
      exchange programs.

PMID- 29067857
TI  - 25-Hydroxy vitamin D levels in premenopausal Turkish women with uterine
      leiomyoma.
AB  - We aimed to evaluate the relationship between serum 25-hydroxy vitamin D levels
      and the risk of uterine fibroids in premenopausal women in Turkish population in
      this prospective observational cross-sectional study. Sixty-eight women with at
      least one uterine leiomyoma >=10 mm were compared with 56 healthy controls. Serum
      25-(OH) vitamin D3 levels were measured by electrochemiluminescence immunoassay.
      The groups were similar in terms of age, BMI, gravidity and parity numbers. The
      mean level of 25-(OH) D3 were 7.28 +/- 4.94 ng/ml and 78% of patients (n = 97)
      had severe vitamin D deficiency ( < 10 ng/mL). Vitamin D levels were
      significantly lower in the study group (6.54 +/- 4.66 ng/ml vs. 8.18 +/- 5.16
      ng/ml, respectively; p = .009). Vitamin D levels were not correlated with size,
      volume, localization and number of leiomyomas. Traditional covered clothing
      style, low education level and being housewife were risk factors for Vitamin D
      deficiency. This is the first study that investigates the vitamin D levels in
      women with leiomyomas in Turkish population. Influence of vitamin D on uterine
      leiomyoma formation to may lead to new preventive strategies in the future.

PMID- 29067858
TI  - Immune-related intestinal pseudo-obstruction associated with nivolumab treatment
      in a lung cancer patient.
AB  - Immune checkpoint inhibition therapy using targeted monoclonal antibodies is a
      new therapeutic approach with significant survival benefit for patients with
      several cancer types. However, their use can be associated with unique immune
      related adverse effects as a consequence of impaired self-tolerance due to loss
      of T-cell inhibition via a nonselective activation of the immune system.
      Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was recently developed
      for cancer immunotherapy with remarkable responses in nonsmall cell lung cancer
      patients. We present a 62-year-old Caucasian male with recurrent lung
      adenocarcinoma and currently under third-line therapy with nivolumab, who was
      admitted in our hospital with abdominal distension. Radiologic findings were
      consistent with small bowel ileus. After four days of conservative treatment, the
      patient underwent exploratory laparotomy where no cause of ileus was discovered.
      Postoperative the ileus persisted and considering that an adverse effect of the
      immune checkpoint inhibition therapy occurred, the patient received high-dose
      prednisone resulting in gradual improvement of symptoms. Immune checkpoint
      inhibitors may induce adverse effects to unaffected organ systems and tissues
      including the skin, gastrointestinal, hepatic, pulmonary, and endocrine system.
      The mainstay treatment consists of immunosuppression with corticosteroids in the
      majority of cases. As the clinical use of immune checkpoint inhibitors is
      expanding rapidly, there is an emergence of unique immune-related adverse effects
      in a growing patient population. Gaining early awareness is essential in these
      patients in order to ensure prompt diagnosis and management.

PMID- 29067859
TI  - Enhanced recall of disgusting relative to frightening photographs is not due to
      organisation.
AB  - Previous research has shown that disgusting photographs are better remembered
      than frightening photographs, even when the two image types have equivalent
      valence and arousal. However, this work did not control for potential differences
      in organisation between the disgusting and frightening stimuli that could account
      for enhanced memory for disgusting photographs. The current research therefore
      tested whether differences in recall between disgusting and frightening
      photographs persist when differences in organisation are eliminated. Using a set
      of disgusting and frightening photographs matched for interrelatedness, Study 1
      found that participants recalled more disgusting photographs than frightening
      photographs. This effect was mediated by increased attention to the disgusting
      photographs. Study 2 used Latent Semantic Analysis to further interrogate the
      relatedness of the photographs, providing converging evidence that organisation
      does not account for enhanced recall of disgusting photographs. Taken together,
      these results suggest that dimensional models of emotion cannot fully account for
      emotion's effects on episodic memory. Instead, disgust appears to enhance recall
      via a distinctive, attention-mediated mechanism.

PMID- 29067856
TI  - Challenges for intraventricular hemorrhage research and emerging therapeutic
      targets.
AB  - INTRODUCTION: Intraventricular hemorrhage (IVH) affects both premature infants
      and adults. In both demographics, it has high mortality and morbidity. There is
      no FDA approved therapy that improves neurological outcome in either population
      highlighting the need for additional focus on therapeutic targets and treatments
      emerging from preclinical studies. Areas covered: IVH induces both initial injury
      linked to the physical effects of the blood (mass effect) and secondary injury
      linked to the brain response to the hemorrhage. Preclinical studies have
      identified multiple secondary injury mechanisms following IVH, and particularly
      the role of blood components (e.g. hemoglobin, iron, thrombin). This review, with
      an emphasis on pre-clinical IVH research, highlights therapeutic targets and
      treatments that may be of use in prevention, acute care, or repair of damage.
      Expert opinion: An IVH is a potentially devastating event. Progress has been made
      in elucidating injury mechanisms, but this has still to translate to the clinic.
      Some pathways involved in injury also have beneficial effects (coagulation
      cascade/inflammation). A greater understanding of the downstream pathways
      involved in those pathways may allow therapeutic development. Iron chelation
      (deferoxamine) is in clinical trial for intracerebral hemorrhage and preclinical
      data suggest it may be a potential treatment for IVH.

PMID- 29067862
TI  - Molecular inhibitory mechanism of dihydromyricetin on mushroom tyrosinase.
AB  - Tyrosinase is the rate-limiting enzyme for controlling the production of melanin
      in the human body, and overproduction of melanin can lead to a variety of skin
      disorders. In this paper, the inhibitory kinetics of Dihydromyricetin (DHM) on
      tyrosinase and their binding mechanism were determined using spectroscopy,
      molecular docking, antioxidant assays, and chromatography. The spectroscopic
      results indicate that DHM reversibly inhibits tyrosinase in a mixed-type manner
      through a multiphase kinetic process with the IC50 of 849.88 MUM. It is shown
      that DHM has a strong ability to quench the intrinsic fluorescence of tyrosinase
      mainly through a static quenching procedure, suggesting that a stable DHM
      tyrosinase complex is generated. Molecular docking results suggest that the
      dominant conformation of DHM does not directly bind to the active site of
      tyrosinase. Moreover, the antioxidant assays demonstrate that DHM has powerful
      antioxidant and reducing capacity but does not have the ability to reduce
      dopachrome to L-DOPA. Interestingly, the results of spectroscopy and
      chromatography indicate that DHM is a substrate of tyrosinase but not a suicide
      substrate. The possible inhibitory mechanism is proposed, which will be helpful
      to design and search for tyrosinase inhibitors.

PMID- 29067861
TI  - Acceptability and feasibility of a financial incentive intervention to improve
      retention in HIV care among pregnant women in Johannesburg, South Africa.
AB  - Women initiating antiretroviral therapy during pregnancy are at high risk of
      dropping out of HIV care after delivery. We assessed the acceptability and
      feasibility of a financial incentive - a one-time R50 (~USD4) supermarket voucher
      for completing one postpartum visit <=10 weeks of delivery - to improve
      postpartum retention. We enrolled 100 pregnant, HIV-positive women at a primary
      health clinic in Johannesburg, South Africa. Participants were interviewed at
      enrollment and we reviewed files to assess retention >=14 weeks postpartum.
      Median (IQR) respondent age was 28 years (24-31) and 31% were employed. Most
      (86%) said the incentive would motivate them to return and 76% supported clinics
      offering incentives. Among the 23% who found the intervention unacceptable, the
      most frequent reason was perceived personal responsibility for health.
      Feasibility was demonstrated, as 79.7% (51/64) of eligible participants received
      a voucher. When asked to rank preferred hypothetical incentive interventions,
      assistance with social services ranked first (29%), followed by infant formula
      (22%) and cash (21%); assistance with social services was the top-ranked choice
      by both those who found the voucher incentive intervention acceptable and
      unacceptable. To encourage HIV-positive women to remain in care, respondents most
      frequently suggested health education (34%), counseling (29%), financial
      incentives (25%), home visits (13%), and better service (6%). Our results suggest
      financial incentives are acceptable, but women frequently expressed preference
      for integrated services and improved education and counseling to improve
      retention. Interventions exploring the feasibility and efficacy of education and
      counseling interventions to improve postpartum HIV care are warranted.

PMID- 29067863
TI  - Prevalence Rate and Course of Symptoms of Disruptive Mood Dysregulation Disorder
      (DMDD).
AB  - Objective: According to DSM-5, Disruptive Mood Dysregulation Disorder (DMDD) is
      characterized by chronic temper outbursts and irritable moods. So far, little is
      known about its prevalence rate, course and influence on individual well-being.
      We assessed the prevalence rates of DMDD symptoms during adulthood and primary
      school age - the latter retrospectively - and studied their relationship with
      psychiatric disorders and socioeconomic variables. Methods: A total of 2,413
      subjects, aged 18-94 years, participated in this population-based, representative
      study based on self-reports. Results: 12 (0.50 %) subjects reported elevated DMDD
      symptoms during adulthood, and 19 (0.79 %) reported elevated DMDD symptoms during
      primary school age. DMDD symptoms were associated with higher rates of depression
      and anxiety symptoms. Those reporting elevated DMDD symptoms during adulthood
      were more often single or divorced, and those reporting elevated DMDD symptoms
      during primary school age were more often childless and unemployed during
      adulthood compared to subjects without DMDD symptoms. Conclusions: DMDD symptoms
      seem to show a chronic course and go hand in hand with elevated psychiatric
      symptoms and impaired socioeconomic and demographic status.

PMID- 29067865
TI  - Isolation and structural identification of a novel minoxidil analogue in an
      illegal dietary supplement: triaminodil.
AB  - A new minoxidil analogue was detected in an illegal dietary supplement advertised
      as a hair-growth treatment. The analogue was identified using ultra-performance
      liquid chromatography (UPLC), high-resolution mass spectrometry (LC-HR-MS) and
      nuclear magnetic resonance (NMR) spectroscopy. The compound was structurally
      elucidated as a minoxidil analogue in which the piperidinyl group of minoxidil
      was replaced with a pyrrolidinyl group corresponding to a molecular formula of
      C8H13N5O. The new analogue has been named triaminodil. As this is the first
      report of the compound, there are no chemical, toxicology or pharmacological data
      available.

PMID- 29067864
TI  - Stress, Substance Use, and Yoga in the Context of Community Reentry Following
      Incarceration.
AB  - This field report provides a rationale for the potential of yoga to support
      reductions in stress and substance use among people returning to the community
      from jail or prison and describes an agency-based example of yoga classes offered
      in this context. People who have recently experienced incarceration face a
      multitude of stressors, which can heighten the risk of substance use and support
      the need to address stress reduction as a pathway to reduced substance use. One
      promising intervention is yoga, which has demonstrated significant stress
      reduction effects among several populations. Feedback from participants in this
      field report's practice example reinforces the potential for yoga to decrease
      stress and complement substance use treatment in supporting health during the
      transition from incarceration to community return. Further scholarship is needed
      to explore the benefits and limitations of yoga in this context.

PMID- 29067866
TI  - The unexpected killer: effects of stimulus threat and negative affectivity on
      inattentional blindness.
AB  - Inattentional blindness (IB) occurs when observers fail to detect unexpected
      objects or events. Despite the adaptive importance of detecting unexpected
      threats, relatively little research has examined how stimulus threat influences
      IB. The current study was designed to explore the effects of stimulus threat on
      IB. Past research has also demonstrated that individuals with elevated negative
      affectivity have an attentional bias towards threat-related stimuli; therefore,
      the current study also examined whether state and trait levels of negative
      affectivity predicted IB for threat-related stimuli. One hundred and eleven
      participants (87 female, aged 17-40 years) completed an IB task that included
      both threat-related and neutral unexpected stimuli, while their eye movements
      were tracked. Participants were significantly more likely to detect the
      threatening stimulus (19%) than the neutral stimulus (11%) p  =  .035, odds ratio
      (OR)  =  4.0, 95% confidence interval OR [1.13, 14.17]. Neither state nor trait
      levels of negative affectivity were significantly associated with IB. These
      results suggest observers are more likely to detect threat-related unexpected
      objects, consistent with the threat superiority effect observed in other
      paradigms. However, most observers were blind to both unexpected stimuli,
      highlighting the profound influence of expectations and task demands on our
      ability to perceive even potentially urgent and life-threatening information.

PMID- 29067868
TI  - A 10-fold bolus dose of N-acetylcysteine with fatal consequences.

PMID- 29067867
TI  - Comparison of transcutaneous electrical nerve stimulation (TENS) and functional
      electrical stimulation (FES) for spasticity in spinal cord injury - A pilot
      randomized cross-over trial.
AB  - OBJECTIVE: Spasticity following spinal cord injury (SCI) can impair function and
      affect quality of life. This study compared the effects of transcutaneous
      electrical nerve stimulation (TENS) and functional electrical stimulation (FES)
      on lower limb spasticity in patients with SCI. DESIGN: Double blind randomized
      crossover design. SETTING: Neuro-rehabilitation unit, Manipal University, India.
      PARTICIPANTS: Ten participants (age: 39 +/- 13.6 years, C1-T11, 1-26 months post
      SCI) with lower limb spasticity were enrolled in this study. INTERVENTIONS:
      Participants were administered electrical stimulation with TENS and FES (duration
      - 30 minutes) in a cross over manner separated by 24 hours. OUTCOME MEASURES:
      Spasticity was measured using modified Ashworth scale (MAS) [for hip abductors,
      knee extensors and ankle plantar flexors] and spinal cord assessment tool for
      spastic reflexes (SCATS). Assessments were performed at baseline, immediately, 1
      hour, 4 hours, and 24 hours post intervention. RESULTS: A between group analysis
      did not show statistically significant differences between FES and TENS (P >
      0.05). In the within group analyses, TENS and FES significantly reduced
      spasticity up to 4 hours in hip adductors and knee extensors (P < 0.01). SCATS
      values showed significant reductions at 1 hour (P = 0.01) following TENS and 4
      hours following FES (P = 0.01). CONCLUSION: A single session of electrical
      stimulation with FES and TENS appears to have similar anti-spasticity effects
      that last for 4 hours. The findings of this preliminary study suggest that both
      TENS and FES have the potential to be used as therapeutic adjuncts to relieve
      spasticity in the clinic. In addition, FES may have better effects on patients
      presenting with spastic reflexes.

PMID- 29067870
TI  - Medical Teacher in Ten Minutes.

PMID- 29067869
TI  - Top-rated AMEE MedEdPublish Papers - mid-June to July 2017.

PMID- 29067871
TI  - Antiphospholipid syndrome and IgA anti-beta2-glycoprotein I antibodies: when
      Cinderella becomes a princess.
AB  - IgA anti-beta2-glycoprotein I (IgA-aB2GPI) antibodies are currently not included
      as a laboratory criterion of antiphospholipid syndrome (APS). In the 13th
      International Congress on Antiphospholipid Antibodies, Galveston, TX, (USA) in
      2010, these antibodies were accepted as an APS laboratory criterion in patients
      who had clinical manifestations of APS but were negative for "consensus"
      antiphospholipid antibodies (aPL) (IgG and IgM isotypes). Consequently,
      individuals with thrombotic events who are negative for consensus aPL may be
      undiagnosed for APS. The most recent publications have confirmed that IgA-aB2GPI
      antibodies are a risk factor for thrombotic events. In this viewpoint, we propose
      that IgA-aB2GPI antibodies should be included as an APS consensus criterion and
      that we have to help Cinderella become a princess.

PMID- 29067873
TI  - Editorial Board Page.

PMID- 29067872
TI  - Selective neural sensitivity to familial threat in adolescents with weak family
      bonds.
AB  - Familial stressors, such as weak familial connectedness, are associated with the
      development of maladaptive threat processing, yet little is known regarding how
      weak familial bonds impinge on biological mechanisms of threat processing. The
      present study leveraged multivoxel pattern analysis of fMRI data to compare the
      neural encoding of familial and nonfamilial threatening and non-threatening
      stimuli in adolescents who endorsed varying levels of connectedness to their
      families. Adolescents (N = 22, Mage = 14.38 years) reporting lower family
      connectedness 1 year earlier showed elevated sensitivity to familial threat, but
      not to nonfamilial threat in a neural network associated with threat processing,
      comprising left and right amygdala, and right inferior and middle temporal gyri.
      Results suggest that a learning history about one's social environment may shape
      neural mechanisms of threat processing by sensitizing them to risk-relevant
      stimuli. Such findings advance our understanding of how familial stressors
      contribute to disordered threat processing in adolescence.

PMID- 29067875
TI  - A simple mathematical model for Ebola in Africa.
AB  - We deal with the following question: Can the consumption of contaminated bush
      meat, the funeral practices and the environmental contamination explain the
      recurrence and persistence of Ebola virus disease outbreaks in Africa? We develop
      an SIR-type model which, incorporates both the direct and indirect transmissions
      in such a manner that there is a provision of Ebola viruses. We prove that the
      full model has one (endemic) equilibrium which is locally asymptotically stable
      whereas, it is globally asymptotically stable in the absence of the Ebola virus
      shedding in the environment. For the sub-model without the provision of Ebola
      viruses, the disease dies out or stabilizes globally at an endemic equilibrium.
      At the endemic level, the number of infectious is larger for the full model than
      for the sub-model without provision of Ebola viruses. We design a nonstandard
      finite difference scheme, which preserves the dynamics of the model. Numerical
      simulations are provided.

PMID- 29067874
TI  - Analysis of a time-delayed mathematical model for tumour growth with an almost
      periodic supply of external nutrients.
AB  - In this paper, the existence, uniqueness and exponential stability of almost
      periodic solutions for a mathematical model of tumour growth are studied. The
      establishment of the model is based on the reaction-diffusion dynamics and mass
      conservation law and is considered with a delay in the cell proliferation
      process. Using a fixed-point theorem in cones, the existence and uniqueness of
      almost periodic solutions for different parameter values of the model is proved.
      Moreover, by the Gronwall inequality, sufficient conditions are established for
      the exponential stability of the unique almost periodic solution. Results are
      illustrated by computer simulations.

PMID- 29067876
TI  - Australian doctors' knowledge of and compliance with the law relating to end-of
      life decisions: implications for LGBTI patients.
AB  - In most developed countries, competent patients have the legal right to refuse
      any medical treatment; Advance Care Planning mechanisms extend this right to non
      competent patients. However, some groups, including lesbian, gay, bisexual,
      transgender and intersex (LGBTI) people, risk their wishes not being respected if
      they lose capacity, more than others. Little is known about medical
      practitioners' knowledge of, or attitudes to, the law in this area, especially in
      relation to LGBTI people, or how the law influences their decision-making. An
      Australian postal survey explored knowledge and attitudes of medical specialists
      to legal issues relating to withdrawing/ withholding life-sustaining treatment
      from adults without capacity. One scenario (the focus of this paper) asked which
      of four plausible substitute decision-makers, including a same-sex partner, had
      the legal authority to make such decisions. The overall response rate was 32%
      (867/2702). Less than one-third of respondents correctly identified the same-sex
      partner as the legally authorised decision-maker. LGBTI people face multiple
      obstacles to having their end-of-life wishes respected. Where healthcare
      providers are also ignorant of the partner's legal right to make such decisions,
      the problem is compounded. Improved legal education for clinicians and promotion
      of educational resources for members of the LGBTI community is needed.

PMID- 29067877
TI  - Somatostatin analogs in the treatment of neuroendocrine tumors: current and
      emerging aspects.
AB  - INTRODUCTION: Neuroendocrine tumors (NETs) harbor somatostatin receptors and
      there is a strong rationale for using somatostatin analogs (SSAs) for treatment
      of NETs. Areas covered: This article discusses i) pharmacology of somatostatin
      and its analogs; ii) antisecretory and anti-proliferative effects of SSAs in
      NETs; iii) efficacy and safety of emerging therapeutic regimens with first
      generation SSAs administered at either high doses or in combination with
      antineoplastic drugs; iv) efficacy and safety of pasireotide and chimeric
      molecules; v) efficacy of radionuclide therapy of NETs using SSAs. Expert
      opinion: SSAs are the first-line medical therapy for functioning and non
      functioning well-differentiated NETs. In patients not responder to first
      generation SSAs, the increase of drug dose over the conventional regimens, the
      combination of SSAs with other biotherapies or molecular targeted therapies, the
      switch to pasireotide or the use of SSAs in radionuclide therapy may improve the
      therapeutic success.

PMID- 29067879
TI  - Expression of Disialoganglioside (GD2) in Neuroblastic Tumors: A Prognostic Value
      for Patients Treated With Anti-GD2 Immunotherapy.
AB  - Neuroblastoma, a malignant neoplasm of the sympathetic nervous system, is one of
      the most aggressive pediatric cancers. Patients with stage IV high-risk
      neuroblastoma receive an intensive multimodal therapy ending with an
      immunotherapy based on a chimeric monoclonal antibody ch14.18. Although the use
      of ch14.18 monoclonal antibody has significantly increased the survival rate of
      high-risk neuroblastoma patients, about 33% of these patients still relapse and
      die from their disease. Ch14.18 targets the disialoganglioside, GD2, expressed on
      neuroblastic tumor (NT) cells. To better understand the causes of tumor relapse
      following ch14.18 immunotherapy, we have analyzed the expression of GD2 in 152
      tumor samples from patients with NTs using immunohistochemical stainings. We
      observed GD2 expression in 146 of 152 samples (96%); however, the proportion of
      GD2-positive cells varied among samples. Interestingly, low percentage of GD2
      positive cells before immunotherapy was associated with relapse in patients
      receiving ch14.18 immunotherapy. In addition, we demonstrated in vitro that the
      sensitivity of neuroblastoma cell lines to natural killer-mediated lysis was
      dependent on the proportion of GD2-positive cells, in the presence of ch14.18
      antibody. In conclusion, our results indicate that the proportion of tumor cells
      expressing GD2 in NTs should be taken in consideration, as a prognostic marker,
      for high-risk neuroblastoma patients receiving anti-GD2 immunotherapy.

PMID- 29067878
TI  - Brain Penetration of the ROS1/ALK Inhibitor Lorlatinib Confirmed by PET.
AB  - The Massachusetts General Hospital Radiochemistry Program, in collaboration with
      Pfizer, has developed unique 11C and 18F-labeling strategies to synthesize
      isotopologs of lorlatinib (PF-06463922) which is undergoing phase III clinical
      trial investigations for treatment of non-small-cell lung cancers with specific
      molecular alterations. A major goal in cancer therapeutics is to measure the
      concentrations of this drug in the brain metastases of patients with lung cancer,
      and penetration of the blood-brain barrier is important for optimal therapeutic
      outcomes. Our recent publication in Nature Communications employed radiolabeled
      lorlatinib and positron emission tomography (PET) studies in preclinical models
      including nonhuman primates (NHPs) that demonstrated high brain permeability of
      this compound. Our future work with radiolabeled lorlatinib will include advanced
      PET evaluations in rodent tumor models and normal NHPs with the goal of clinical
      translation.

PMID- 29067880
TI  - Modulating affective experience and emotional intelligence with loving kindness
      meditation and transcranial direct current stimulation: A pilot study.
AB  - Positive emotional perceptions and healthy emotional intelligence (EI) are
      important for social functioning. In this study, we investigated whether loving
      kindness meditation (LKM) combined with anodal transcranial direct current
      stimulation (tDCS) would facilitate improvements in EI and changes in affective
      experience of visual stimuli. LKM has been shown to increase positive emotional
      experiences and we hypothesized that tDCS could enhance these effects. Eighty
      seven undergraduates were randomly assigned to 30 minutes of LKM or a relaxation
      control recording with anodal tDCS applied to the left dorsolateral prefrontal
      cortex (left dlPFC) or right temporoparietal junction (right TPJ) at 0.1 or 2.0
      milliamps. The primary outcomes were self-reported affect ratings of images from
      the International Affective Picture System and EI as measured by the Mayer,
      Salovey and Caruso Emotional Intelligence Test. Results indicated no effects of
      training on EI, and no main effects of LKM, electrode placement, or tDCS current
      strength on affect ratings. There was a significant interaction of electrode
      placement by meditation condition (p = 0.001), such that those assigned to LKM
      and right TPJ tDCS, regardless of current strength, rated neutral and positive
      images more positively after training. Results suggest that LKM may enhance
      positive affective experience.

PMID- 29067881
TI  - Autologous cytokine-induced killer cell immunotherapy may improve overall
      survival in advanced malignant melanoma patients.
AB  - AIMS: Our study was conducted to explore the efficacy of autologous cytokine
      induced killer (CIK) cells in patients with advanced malignant melanoma.
      Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients
      among which 68 patients received CIK cell immunotherapy alone, while 45 patients
      accepted CIK cell therapy combined with chemotherapy. Results: We found that the
      median survival time in CIK cell group was longer than the combined therapy group
      (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as
      monocyte proportion and lymphocyte count were associated with patients' survival
      time. CONCLUSIONS: These indicated that CIK cell immunotherapy might extend
      survival time in advanced malignant melanoma patients. Furthermore, serum
      hemoglobin level, monocyte proportion and lymphocyte count could be prognostic
      indicators for melanoma.

PMID- 29067882
TI  - Alicaforsen in the treatment of pouchitis.
AB  - Alicaforsen is a 20-base antisense oligonucleotide inhibiting ICAM-1 production,
      which is an important adhesion molecule involved in leukocyte migration and
      trafficking to the site of inflammation. Hitherto, alicaforsen has been granted
      orphan drug designation and is prescribed as an unlicensed medicine in accordance
      with international regulation for the treatment of pouchitis and left-sided
      ulcerative colitis. Given the positive results evolving from one open-label trial
      and one case series in patients with chronic refractory pouchitis, US FDA has
      agreed to a rolling submission for a license application for the treatment of
      pouchitis, which has been recently initiated. Whether alicaforsen leads to higher
      endoscopic and clinical remission rates as placebo and whether the response can
      be maintained in the long-term in larger studies is yet unknown. An ongoing
      multicenter international Phase III trial will definitely address these
      unanswered questions.

PMID- 29067883
TI  - The link between calcitriol and anticancer immunotherapy: vitamin D as the
      possible balance between inflammation and autoimmunity in the immune-checkpoint
      blockade.

PMID- 29067884
TI  - Immune-related musculoskeletal toxicities among cancer patients treated with
      immune checkpoint inhibitors: a systematic review.
AB  - AIM: Immune-related musculoskeletal toxicities are uncommon but potentially
      serious adverse events; and they may accompany the use of immune checkpoint
      inhibitors (ICIs). The objective of this systematic review is to assess the
      patterns of these musculoskeletal toxicities. METHODS & RESULTS: PubMed database
      has been searched till May 2017. Clinical studies and case reports reporting the
      occurrence of immune-related musculoskeletal toxicities (other than arthralgia
      and myalgia) in cancer patients treated with ICIs were included. Eight trials
      with 2263 participants were included. Likewise, nine case reports reporting the
      outcomes of 12 patients were included. CONCLUSION: Immune-related arthritis and
      myositis occur uncommonly in cancer patients treated with ICIs. Further studies
      are required to better describe the pathogenesis as well as the time course of
      these events.

PMID- 29067885
TI  - A review article on biosimilar infliximab SB2 in the treatment of rheumatoid
      arthritis.
AB  - TNF inhibition has had a major impact as an approach for treating rheumatoid
      arthritis and a series of biologic agents directed against TNF have been
      developed for clinical use. Infliximab, a chimeric monoclonal antibody against
      soluble and membrane-bound TNF-alpha, was the biopharmaceutical to lead this
      'biologics revolution'. However, with expiration of patent protection of the
      originator medicinal product, biosimilar versions of infliximab have been
      developed through biosimilarity studies and randomized controlled trials aiming
      to assess pharmacokinetic, pharmacodynamic and clinical equivalence to their
      originator (reference product) in patients with moderate-to-severe disease
      activity. This review summarizes the clinical development of SB2, a biosimilar of
      infliximab, in rheumatoid arthritis.

PMID- 29067886
TI  - Sphingolipid pathway enzymes modulate cell fate and immune responses.
AB  - Sphingolipids (SLs) are a class of essential, bioactive lipids. The SL family
      includes over 4000 distinct molecules, characterized by their sphingoid base
      (long-chain aliphatic amine) backbone. SLs are key components of cell membranes,
      yet their roles go well beyond structure. SLs are involved in many cellular
      processes including cell differentiation, apoptosis, growth arrest and
      senescence. As cancer cells routinely display increased growth properties and
      escape from cell death, it has been suggested that enzymes involved in SL
      synthesis or catabolism may be altered in cancer cells. In this review, we
      discuss the role of SL pathway enzymes in cancer, and in acquired resistance to
      therapy. The use of inhibitors and gene silencing approaches targeting these SL
      pathways is also explored. Finally, we elaborate on the role of SL pathway
      enzymes in the tumor microenvironment and their effect on immune cell function.

PMID- 29067888
TI  - Lithium-induced gene expression alterations in two peripheral cell models of
      bipolar disorder.
AB  - OBJECTIVES: The aim of our study was to investigate molecular mechanisms of
      lithium action by studying the gene expression profile of peripheral cell models
      generated from bipolar patients (BD) and healthy controls (HC). METHODS: EBV
      immortalised lymphoblastoid cells (LCLs) and fibroblast cells from BD and HC were
      incubated with either lithium chloride or plain medium for 3 weeks. We first
      conducted a microarray gene expression study. The most promising differentially
      regulated genes in terms of lithium-associated or disorder-associated pathways
      were then replicated by quantitative real-time PCR (qRT-PCR). RESULTS: The pooled
      microarray analysis showed 459 genes to be differentially regulated in BD
      compared to HC and 58 due to lithium treatment in LCLs, and 295 genes to be
      differentially regulated in BD compared to HC and five due to lithium treatment
      in fibroblasts. After correction for multiple comparison, EPHB1 disorder *
      treatment interactions remained significant in LCLs validated by qRT-PCR. In the
      control group, lithium influenced the expression of ANP32E, PLEKHA2, KCNK1,
      PRKCH, ST3GAL6 and AIF1. In bipolar and control fibroblast cells lithium
      treatment decreased FGF9 expression. CONCLUSIONS: The differentially regulated
      genes in our study add evidence for the relevance of inflammation, neuronal/glial
      development, phosphatidylinositol second-messenger pathway and ion channels in
      the mode of action of lithium.

PMID- 29067889
TI  - All quiet on the front of fibromuscular dysplasia?

PMID- 29067887
TI  - Effects of a cafeteria diet on delay discounting in adolescent and adult rats:
      Alterations on dopaminergic sensitivity.
AB  - Diet-induced obesity is a laboratory procedure in which nonhuman animals are
      chronically exposed to a high-fat, high-sugar diet (i.e. cafeteria diet), which
      results in weight gain, altered sensitivity to reward, and alterations in the
      dopamine D2 system. To date, few (if any) studies have examined age-related diet
      induced obesity effects in a rat model or have used an impulsive choice task to
      characterize diet-induced behavioral alterations in reward processes. We exposed
      rats to a cafeteria-style diet for eight weeks starting at age 21 or 70 days.
      Following the diet exposures, the rats were tested on a delay discounting task -
      a measure of impulsive choice in which preference for smaller, immediate vs
      larger, delayed food reinforcers was assessed. Acute injections of haloperidol
      (0.03-0.3 mg/kg) were administered to assess the extent to which diet-induced
      changes in dopamine D2 influence impulsive food choice. Across both age groups,
      rats fed a cafeteria diet gained the most weight and consumed more calories than
      rats fed a standard diet, with rats exposed during development showing the
      highest weight gain. No age- or diet-related baseline differences in delay
      discounting were revealed, however, haloperidol unmasked subtle diet-related
      differences by dose-dependently reducing choice for the larger, later reinforcer.
      Rats fed a cafeteria diet showed a leftward shift in the dose-response curve,
      suggesting heightened sensitivity to haloperidol, regardless of age, compared to
      rats fed a standard diet. Results indicate that chronic exposure to a cafeteria
      diet resulted in changes in underlying dopamine D2 that manifested as greater
      impulsivity independent of age at diet exposure.

PMID- 29067890
TI  - DeGIR-/DGNR training programme in interventional radiology and neuroradiology.

PMID- 29067891
TI  - Determination of diffusion and partition coefficients of model migrants by direct
      contact and vapour phase transfer from low-density polyethylene films into cake.
AB  - The aim of the present study was to determine the migration kinetics of one
      photoinitiator, benzophenone, and two optical brighteners, Uvitex OB and 1,4
      diphenyl-1,3-butadiene (DPBD), from low-density polyethylene (LDPE) films into
      cake. Transfer was assessed by both direct contact and also the vapour phase. To
      perform the migration tests by direct contact, plastic films enriched with the
      additives were placed between two cake slices. To evaluate the migration through
      the gas phase, cake and the fortified LDPE film were placed with no direct
      contact in a glass container that was hermetically closed. Samples were stored at
      different time-temperature conditions. Target compounds were extracted from the
      films with ethanol (70 degrees C, 24 h) and analysed by HPLC-DAD. Relevant
      parameters such as partition and diffusion coefficients between food and plastic
      film were calculated. The Arrhenius equation was applied to estimate the
      diffusion coefficient at any temperature. The data indicate that migration of
      benzophenone occurs in a significant extent into cake by both direct contact and
      through the gas phase (no direct contact). Conversely, very little migration
      occurred for Uvitex OB by direct contact and none through the gas phase. Results
      for benzophenone suggest that migration through the gas phase should be
      considered when evaluating migration from food packaging materials into food.

PMID- 29067892
TI  - Corrigendum.

PMID- 29067893
TI  - Laryngomalacia: is there an evidence base for management?
AB  - BACKGROUND: The advent of supraglottoplasty clearly has transformed the surgical
      management of severe laryngomalacia. The condition, however, generally runs a
      milder course, with spontaneous resolution the norm. OBJECTIVES: To identify gaps
      in the knowledge and identify topics for future study. METHOD: Systematic review
      of the literature. RESULTS: The literature suggests that there is a range of
      abnormalities leading to the typical collapsing upper airway, and that
      neurological disease, other airway abnormalities, syndromes and gastroesophageal
      reflux all contribute to disease severity and influence outcomes. The procedures
      involved in supraglottoplasty are rarely specified, the indications for surgery
      are vaguely defined and the role of medical therapy is unclear. CONCLUSION: Every
      review article or survey of opinion suggests that there is still a marked
      variation in individual practice and a lack of consensus.

PMID- 29067894
TI  - Mansonella ozzardi and its vectors in the New World: an update with emphasis on
      the current situation in Haiti.
AB  - Mansonella ozzardi (Nematoda: Onchocercidae) is a little studied filarial
      nematode. This human parasite, transmitted by two families of dipteran vectors,
      biting midges (most of them members of the genus Culicoides) and blackflies
      (genus Simulium), is endemic to the Neotropical regions of the New World. With a
      patchy geographical distribution from southern Mexico to north-western Argentina,
      human infection with M. ozzardi is highly prevalent in some of the Caribbean
      islands, along riverine communities in the Amazon Basin, and on both sides of the
      border between Bolivia and Argentina. Studies conducted in Haiti between 1974 and
      1984 allowed the first complete description of the adult worm and permitted
      clarification of the taxonomic position of this filarial species. This paper
      reports the known geographical distribution of M. ozzardi in Neotropical regions
      of the Americas, and focuses on the current situation in Haiti where this
      filariasis remains a completely neglected public health problem.

PMID- 29067895
TI  - In vitro anthelmintic and cytotoxic activities of extracts of Persea willdenovii
      Kosterm (Lauraceae).
AB  - This study describes the effects of extracts and fractions of Persea willdenovii
      leaves against goat gastrointestinal nematodes and their cytotoxicity on Vero
      cells. The in vitro ovicidal and larvicidal activities of the crude ethanolic,
      hexane, ethyl acetate (EAE), butanolic and residual hydroethanolic extracts were
      assessed through the inhibition of egg hatching and larval motility assays. The
      most active extract (EAE) was then fractionated by chromatography in an open
      column containing silica gel, to furnish six fractions (Fr1-Fr6), which were also
      tested. The cytotoxicity of active extracts and fractions was determined using
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and
      trypan blue exclusion assay. The EAE and two fractions (Fr1 and Fr2) showed
      inhibitory activity in the egg hatching of gastrointestinal nematodes of goats in
      a concentration-dependent manner. The effective concentrations for 50% inhibition
      (EC50) of egg hatching were 2.3, 0.12 and 2.94 mg/ml for EAE, Fr1 and Fr2,
      respectively. All extracts and fractions were not effective in inhibiting 50% of
      motility of infective larvae. EAE and Fr2 had IC50 values (50% inhibitory
      concentration) of 4.95 and 2.66 mg/ml, respectively. Fr1 showed a slight
      cytotoxic effect (cellular inviability <30%) only after 48 h of treatment (MTT
      test). Gas chromatography-mass spectrometry (GC-MS) analysis showed the presence
      of six fatty acid ethyl esters, a fatty acid methyl ester and a long-chain ketone
      in the most active fraction. These constituents identified in P. willdenovii can
      be related to the high ovicidal activity and relatively non-toxic effect of the
      extracts.

PMID- 29067896
TI  - Why do children pay more attention to grammatical morphemes at the ends of
      sentences?
AB  - Children pay more attention to the beginnings and ends of sentences rather than
      the middle. In natural speech, ends of sentences are prosodically and segmentally
      enhanced; they are also privileged by sensory and recall advantages. We
      contrasted whether acoustic enhancement or sensory and recall-related advantages
      are necessary and sufficient for the salience of grammatical morphemes at the
      ends of sentences. We measured 22-month-olds' listening times to grammatical and
      ungrammatical sentences with third person singular -s. Crucially, by cross
      splicing the speech stimuli, acoustic enhancement and sensory and recall
      advantages were fully crossed. Only children presented with the verb in sentence
      final position, a position with sensory and recall advantages, distinguished
      between the grammatical and ungrammatical sentences. Thus, sensory and recall
      advantages alone were necessary and sufficient to make grammatical morphemes at
      ends of sentences salient. These general processing constraints privilege ends of
      sentences over middles, regardless of the acoustic enhancement.

PMID- 29067897
TI  - Peer Comparison of Anti-MRSA Agent Prescription in the Inpatient Setting.
AB  - Peer comparison has potential as an effective antimicrobial stewardship
      intervention in the inpatient setting. We report a new metric, days of therapy
      per 100 service days, for comparing antibiotic utilization. Among 14 prescribers
      on the primary infectious diseases service during a 6-month period, we identified
      1 outlier for each anti-MRSA agent. Infect Control Hosp Epidemiol 2017;38:1506
      1508.

PMID- 29067898
TI  - Fish-borne nematodiases in South America: neglected emerging diseases.
AB  - Fish-borne zoonotic nematodes may infect humans when fish or squid are ingested
      raw or inadequately cooked. Human infections may have serious consequences,
      including the unexpected deaths of infected people. This kind of disease is
      poorly known in general, and the characteristics of such infections in South
      American countries as a whole have never been assessed. In this paper the present
      status of fish-borne nematodiases in humans in South American countries is
      characterized. Potentially zoonotic nematode species are very common in both
      freshwater and marine fish in South America. Reports of human infections have
      only been found in some countries, and their incidence (especially with anisakids
      and Gnathostoma spp.) varies from country to country. Apparently they are more
      abundant in countries with strong traditions of eating raw fish, and are more
      frequent on the western coast of South America. So far fish-borne nematodes have
      been reported in Argentina, Brazil, Chile, Colombia, Ecuador and Peru. In recent
      years, cases of human infection have appeared in probably underestimated numbers.
      People need to be clearly informed about risky feeding habits, and physicians
      need to learn more about zoonotic diseases.

PMID- 29067899
TI  - Mental health care for adult refugees in high-income countries.
AB  - Approximately one-third of people who have obtained refugee status live in high
      income countries. Over recent years, the number of refugees has been increasing,
      and there are questions on how many of them need mental health care and which
      type of interventions are beneficial. Meta-analyses showed highly variable rates
      of mental disorders in adult refugees. This variability is likely to reflect both
      real differences between groups and contexts, and methodological inconsistencies
      across studies. Overall prevalence rates after resettlement are similar to those
      in host populations. Only post-traumatic stress disorder (PTSD) is more prevalent
      in refugees. In long-term resettled refugees, rates of anxiety and depressive
      disorders are higher and linked to poor social integration. Research on mental
      health care for refugees in high-income countries has been extensive, but often
      of limited methodological quality and with very context-specific findings. The
      existing evidence suggests several general principles of good practice: promoting
      social integration, overcoming barriers to care, facilitating engagement with
      treatment and, when required, providing specific psychological treatments to deal
      with traumatic memories. With respect to the treatment of defined disorders, only
      for the treatment of PTSD there has been substantial refugee-specific research.
      For other diagnostic categories, the same treatment guidelines apply as to other
      groups. More systematic research is required to explore how precisely the general
      principles can be specified and implemented for different groups of refugees and
      in different societal contexts in host countries, and which specific
      interventions are beneficial and cost-effective. Such interventions may utilise
      new communication technologies. Of particular importance are long-term studies to
      identify when mental health interventions are appropriate and to assess outcomes
      over several years. Such research would benefit from sufficient funding, wide
      international collaboration and continuous learning over time and across
      different refugee groups.

PMID- 29067900
TI  - HEALTH RISK TRANSITION AND LOW MORTALITY PATTERNS AMONG A NATIONAL COHORT OF
      ASPIRATIONAL THAI OPEN UNIVERSITY STUDENTS.
AB  - SummaryIn the last 50 years Thailand has achieved advanced demographic and health
      transitions. Many infectious diseases are controlled and infant and maternal
      mortality rates are among the lowest in the region. Within such a low mortality
      setting, however, substantial variations in health persist, with education being
      a major driver. This paper assesses the ongoing mortality transition in Thailand,
      examining relationships between risk factors and mortality outcomes among a large
      nationwide cohort of distance-learning Open University students, as well as
      examining the differential mortality benefit enjoyed by this educated group when
      compared with the general Thai population. The cohort comprised 87,151
      participants, who in 2005 completed a questionnaire collecting detailed
      information on socio-demographics, health behaviours and health outcomes.
      Participants were aged 15-87 at baseline and lived in all regions of the country.
      Cohort members' citizen identification numbers were matched with official death
      registration records to identify mortality among participants. A total of 1401
      deaths were identified up to November 2016. Results show cohort study
      participants experiencing mortality at approximately one-third of the rate of the
      general population in the same age and sex groups. The gap between the mortality
      rates in the two groups widened with increased age. Differential risk factor
      prevalence among the two populations, particularly lower overweight and obesity
      prevalence and lower cigarette smoking rates in the cohort, can explain some of
      this variation. The largely unmeasurable effect of aspiration for life
      improvement through distance education while embedded in their communities is
      shown by this study to have a powerful effect on mortality risk. With overall
      education levels, including higher education, rising in Thailand this growing
      group of educated aspirational Thais may represent future trends in Thai
      mortality. Identifying the drivers and characteristics of this mortality
      variation can help inform policies to provide health services and to help reduce
      mortality in the whole population.

PMID- 29067902
TI  - Economic evaluation of HIV pre-exposure prophylaxis among men-who-have-sex-with
      men in England in 2016.
AB  - Clinical effectiveness of pre-exposure prophylaxis (PrEP) for preventing HIV
      acquisition in men who have sex with men (MSM) at high HIV risk is established. A
      static decision analytical model was constructed to inform policy prioritisation
      in England around cost-effectiveness and budgetary impact of a PrEP programme
      covering 5,000 MSM during an initial high-risk period. National genitourinary
      medicine clinic surveillance data informed key HIV risk assumptions. Pragmatic
      large-scale implementation scenarios were explored. At 86% effectiveness, PrEP
      given to 5,000 MSM at 3.3 per 100 person-years annual HIV incidence, assuming
      risk compensation (20% HIV incidence increase), averted 118 HIV infections over
      remaining lifetimes and was cost saving. Lower effectiveness (64%) gave an
      incremental cost-effectiveness ratio of + GBP 23,500 (EUR 32,000) per quality
      adjusted life year (QALY) gained. Investment of GBP 26.9 million (EUR 36.6
      million) in year-1 breaks even anywhere from year-23 (86% effectiveness) to year
      33 (64% effectiveness). PrEP cost-effectiveness was highly sensitive to year-1
      HIV incidence, PrEP adherence/effectiveness, and antiretroviral drug costs. There
      is much uncertainty around HIV incidence in those given PrEP and
      adherence/effectiveness, especially under programme scale-up. Substantially
      reduced PrEP drug costs are needed to give the necessary assurance of cost
      effectiveness, and for an affordable public health programme of sufficient size.

PMID- 29067903
TI  - Measles outbreak linked to European B3 outbreaks, Wales, United Kingdom, 2017.
AB  - The United Kingdom achieved interrupted endemic measles transmission for 36
      months in 2016. Despite this, ongoing challenges from sporadic measles cases
      typically imported from abroad remain. We summarise a B3 measles genotype
      outbreak in south-east Wales occurring between May and September 2017, linked
      with other European outbreaks, and lessons learnt. Seventeen confirmed cases and
      one probable case occurred principally in education and healthcare-settings. Six
      confirmed cases attended healthcare settings when infectious, without being
      isolated.

PMID- 29067904
TI  - Options for affordable pre-exposure prophylaxis (PrEP) in national HIV prevention
      programmes in Europe.

PMID- 29067905
TI  - Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance
      and intermediate resistance to azithromycin, Denmark, 2017.
AB  - We describe a multidrug-resistant Neisseria gonorrhoeae infection with
      ceftriaxone resistance and azithromycin intermediate resistance in a heterosexual
      man in Denmark, 2017. Whole genome sequencing of the strain GK124 identified MSLT
      ST1903, NG-MAST ST1614 and all relevant resistance determinants including similar
      penA resistance mutations previously described in ceftriaxone-resistant
      gonococcal strains. Although treatment with ceftriaxone 0.5 g plus azithromycin 2
      g was successful, increased awareness of spread of gonococcal strains threatening
      the recommended dual therapy is crucial.

PMID- 29067906
TI  - The Age of BLood Evaluation (ABLE) randomised controlled trial: description of
      the UK-funded arm of the international trial, the UK cost-utility analysis and
      secondary analyses exploring factors associated with health-related quality of
      life and health-care costs during the 12-month follow-up.
AB  - BACKGROUND: At present, red blood cells (RBCs) are stored for up to 42 days prior
      to transfusion. The relative effectiveness and safety of different RBC storage
      times prior to transfusion is uncertain. OBJECTIVE: To assess the clinical
      effectiveness and cost-effectiveness of transfusing fresher RBCs (stored for <= 7
      days) compared with current standard-aged RBCs in critically ill patients
      requiring blood transfusions. DESIGN: The international Age of BLood Evaluation
      (ABLE) trial was a multicentre, randomised, blinded trial undertaken in Canada,
      the UK, the Netherlands and France. The UK trial was funded to contribute
      patients to the international trial and undertake a UK-specific health economic
      evaluation. SETTING: Twenty intensive care units (ICUs) in the UK, as part of 64
      international centres. PARTICIPANTS: Critically ill patients aged >= 18 years (>=
      16 years in Scotland) expected to require mechanical ventilation for >= 48 hours
      and requiring a first RBC transfusion during the first 7 days in the ICU.
      INTERVENTIONS: All decisions to transfuse RBCs were made by clinicians. One
      patient group received exclusively fresh RBCs stored for <= 7 days whenever
      transfusion was required from randomisation until hospital discharge. The other
      group received standard-issue RBCs throughout their hospital stay. MAIN OUTCOME
      MEASURES: The primary outcome was 90-day mortality. Secondary outcomes included
      development of organ dysfunction, new thrombosis, infections and transfusion
      reactions. The primary economic evaluation was a cost-utility analysis. RESULTS:
      The international trial took place between March 2009 and October 2014 (UK
      recruitment took place between January 2012 and October 2014). In total, 1211
      patients were assigned to receive fresh blood and 1219 patients to receive
      standard-aged blood. RBCs were stored for a mean of 6.1 days [standard deviation
      (SD) +/- 4.9 days] in the group allocated to receive fresh blood and 22.0 days
      (SD +/- 8.4 days) in the group allocated to receive standard-aged blood. Patients
      received a mean of 4.3 RBC units (SD +/- 5.2 RBC units) and 4.3 RBC units (SD +/-
      5.5 RBC units) in the groups receiving fresh blood and standard-aged blood,
      respectively. At 90 days, 37.0% of patients in the group allocated to receive
      fresh blood and 35.3% of patients in the group allocated to receive standard-aged
      blood had died {absolute risk difference 1.7% [95% confidence interval (CI) -2.1%
      to 5.5%]}. There were no between-group differences in any secondary outcomes. The
      UK cohort comprised 359 patients randomised and followed up for 12 months for the
      cost-utility analysis. UK patients had similar characteristics and outcomes to
      the international cohort. Mean total costs per patient were L32,346 (95% CI
      L29,306 to L35,385) in the group allocated to receive fresh blood and L33,353
      (95% CI L29,729 to L36,978) in the group allocated to receive standard-aged
      blood. Approximately 85% of the total costs were incurred during the index
      hospital admission. There were no significant cost differences between the two
      groups [mean incremental costs for those receiving fresh vs. standard-aged blood:
      -L231 (95% CI -L4876 to L4415)], nor were there significant differences in
      outcomes (mean difference in quality-adjusted life-years -0.010, 95% CI -0.078 to
      0.057). LIMITATIONS: Adverse effects from the exclusive use of older RBCs
      compared with standard or fresh RBCs cannot be excluded. CONCLUSIONS: The use of
      RBCs aged <= 7 days confers no clinical or economic benefit in critically ill
      patients compared with standard-aged RBCs. FUTURE WORK: Future studies should
      address the safety of RBCs near the end of the current permitted storage age.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN44878718. FUNDING: This
      project was funded by the National Institute for Health Research (NIHR) Health
      Technology Assessment programme and will be published in full in Health
      Technology Assessment; Vol. 21, No. 62. See the NIHR Journals Library website for
      further project information. The international ABLE trial was also supported by
      peer-reviewed grants from the Canadian Institutes of Health Research (177453),
      Fonds de Recherche du Quebec - Sante (24460), the French Ministry of Health
      Programme Hospitalier de Recherche Clinique (12.07, 2011) and by funding from
      Etablissement Francais du Sang and Sanquin Blood Supply.

PMID- 29067907
TI  - How much do we need to provoke? Challenges and opportunities in refining the
      pharmacological tests to unmask Brugada syndrome.

PMID- 29067909
TI  - Atrial flutter presenting as broad complex tachycardia in a patient with right
      sided pneumonectomy.
AB  - A 71-year-old man with no history of coronary artery disease presented with
      palpitations to the emergency department. The 12-lead ECG showed a regular
      tachycardia with wide QRS complexes (220 bpm) suggestive of ventricular
      tachycardia. Instead invasive electrophysiological investigation revealed typical
      atrial flutter as underlying arrhythmia. The altered QRS morphology resulted from
      displacement of the heart into the right hemithorax due to right-sided
      pneumonectomy in combination with bundle branch block.

PMID- 29067908
TI  - Evaluation of baseline ECG in patients undergoing Oral Flecainide Challenge test
      for suspected Brugada Syndrome: An analysis of lead II.
AB  - BACKGROUND AND OBJECTIVES: We analyzed Lead II in patients undergoing an Oral
      Flecainide Challenge test (FCT), to identify any pointers that could predict a
      positive FCT and thereby help in recognition of latent BS. METHODS: The following
      parameters in lead II were retrospectively analyzed from the pre-test ECG in 62
      patients undergoing FCT for suspected BS: The presence or absence of S waves, S
      wave amplitude, duration and upslope duration; J point parameters- Early
      repolarization, QRS notch, and QRS Slur; ST segment parameters-lack of
      isoelectric ST segment, ST duration and QT interval. RESULTS: 48 had positive FCT
      (Group-1) while 14 were negative for FCT(Group-2). Lack of an isoelectric ST
      segment (50% vs 14.29%, p = 0.018) and slurring of QRS (33.33% vs 0%, p = 0.014)
      was more common in Group-1 than Group-2. Group-1 had shorter ST segment duration
      (median 81.5 (IQR 64-103.5) vs 110 (IQR 90-132), p = 0.002) and shorter ST: QT
      ratio (median 0.28 (IQR 0.22-0.35) vs 0.23 (0.18-0.27), p = 0.007). QRS
      notch/depressed J point (87.5%), QRS slur (100%), and lack of isoelectric ST
      segment (92.31%) had high sensitivity for predicting an inducible Type 1 Brugada
      pattern. Combining two parameters- ST: QT ratio<0.24 and lack of isoelectric ST
      segment-considerably improved the specificity (73.3%), and the positive
      predictive value of the test to 76%. The results remained accurate when validated
      in a small prospective cohort. CONCLUSION: Shortened ST segment in Lead II, lack
      of isoelectric ST segment, slurred QRS and ST/QT ratio <0.24 are predictive of
      underlying Brugada pattern in baseline ECG.

PMID- 29067911
TI  - Syncope in a young man: Role of Purkinje fibres in idiopathic ventricular
      fibrillation.
AB  - A young man suffered cardiac arrests with polymorphic ventricular tachycardia
      (PVT) and ventricular fibrillation (VF) triggered by ventricular premature
      contractions (PVCs). The arrhythmia was resistant to anti-arrhythmics, so after
      ICD implantation he underwent successful ablation of the triggering VE beat,
      which was pace-mapped to the left posterior hemi-fascicle. We review the evidence
      for the role of the Purkinje network in the initiation and maintenance of PVT and
      VF, postulating a channelopathy as a possible underlying cause, and provide
      recommendations for PVC ablation.

PMID- 29067910
TI  - First rib and venous anomalies - Anatomical challenges for transvenous
      implantation of cardiac electronic devices.
AB  - Atypical anatomy may be encountered unexpectedly and undiagnosed in clinical
      practice, and this is especially important during the performance of
      interventional procedures such as transvenous implantation of cardiac electronic
      devices. The body of the first rib can be absent. If this not noticed, pneumo
      /haemothroax may be induced during subclavian vein puncture as the needle may
      enter the first intercostal space rather than the costo-clavicular angle. The
      cephalic vein may pursue a supraclavicular course, the axillary vein may drain
      into an intercostal vein rather than the axillary vein, and the entire length of
      the axillary-subclavian-brachio-cephalic vein may be absent. Device implanters
      should be vigilant about the possibility of these anatomical variations, and be
      equipped with the knowledge and spectrum of alternative techniques needed to deal
      with them.

PMID- 29067912
TI  - High density mapping of inappropriate sinus tachycardia further looks into
      potential mechanisms.
AB  - Inappropriate sinus tachycardia (IST) is an incompletely understood condition
      associating unexpectedly fast sinus rates and debilitating symptoms whose
      management by sinus node modification/ablation demonstrated limited long-term
      success. We report about a case of IST who underwent two RF procedures using high
      density mapping system, highlighting some possibly specific features and
      discussing potential mechanisms.

PMID- 29067913
TI  - Narrow QRS tachycardia to wide QRS tachycardia with LBBB morphology. What is the
      mechanism?

PMID- 29067914
TI  - Cryoablation for atrioventricular nodal reentry tachycardia: Role of "mapping"
      and "pseudo-mapping".

PMID- 29067916
TI  - Electrical and thermoelectric transport properties of two-dimensional fermionic
      systems with k-cubic spin-orbit coupling.
AB  - We investigate the effect of k-cubic spin-orbit interaction on the electrical and
      thermoelectric transport properties of two-dimensional fermionic systems. We
      obtain exact analytical expressions of the inverse relaxation time (IRT) and the
      Drude conductivity for long-range Coulomb and short-range delta scattering
      potentials. The IRT reveals that the scattering is completely suppressed along
      the three directions [Formula: see text] with [Formula: see text]. We also obtain
      analytical results of the thermopower and thermal conductivity at low
      temperature. The thermoelectric transport coefficients obey the Wiedemann-Franz
      law, even in the presence of k-cubic Rashba spin-orbit interaction (RSOI) at low
      temperature. In the presence of a quantizing magnetic field, the signature of the
      RSOI is revealed through the appearance of the beating pattern in the Shubnikov
      de Haas (SdH) oscillations of thermopower and thermal conductivity in the low
      magnetic field regime. The empirical formulae for the SdH oscillation frequencies
      accurately describe the locations of the beating nodes. The beating pattern in
      magnetothermoelectric measurement can be used to extract the spin-orbit coupling
      constant.

PMID- 29067915
TI  - Pseudo cryomapping for ablation of atrioventricular nodal reentry tachycardia: A
      single center North American experience.
AB  - BACKGROUND: Most literature for cryoablation of atrioventricular nodal reentry
      tachycardia (AVNRT) is based on -30 degree celsius cryomapping with 4 & 6 mm
      distal electrode catheters. The cryomapping mode is not available on the 6 mm
      cryocatheter in the United States. We describe a technique for 'pseudo' mapping
      at -80 degrees  using a 6 mm cryocatheter and report on short and long term
      outcomes. METHODS: A retrospective analysis of all index cases (n = 253) of
      cryoablation of AVNRT at a single North American institution during the period of
      2003-2010 was performed. The majority of cases utilized a 6 mm distal electrode
      tip catheter. Long term follow up (2.4 +/- 1.8 years) was performed via review of
      the medical record and by questionnaire or telephone if necessary. RESULTS: Acute
      ablation success was achieved in 93% of cases, with transient conduction defects
      noted in 39% of cases, and long term conduction defects in 1.6% of cases (4
      patients with PR prolongation, 2 of which were permanent). General anesthesia,
      male gender and presence of structural heart disease were more common in the
      acute failure cohort. The recurrence rate for AVNRT was 8%. These patients tended
      to be younger and had more transient A-V conduction defects during the index
      procedure than those without a recurrence. CONCLUSIONS: In conclusion, anatomic
      cryoablation of AVNRT utilizing a 6 mm electrode catheter with mapping performed
      at -80 degrees  Celsius is a safe procedure with good long term efficacy.
      Transient A-V block during the index procedure increases the risk of late
      recurrence.

PMID- 29067917
TI  - Magnetization dynamics of weak stripe domains in Fe-N thin films: a multi
      technique complementary approach.
AB  - The resonant eigenmodes of an alpha'-FeN thin film characterized by weak stripe
      domains are investigated by Brillouin light scattering and broadband
      ferromagnetic resonance experiments, assisted by micromagnetic simulations. The
      spectrum of the dynamic eigenmodes in the presence of the weak stripes is very
      rich and two different families of modes can be selectively detected using
      different techniques or different experimental configurations. Attention is paid
      to the evolution of the mode frequencies and spatial profiles under the
      application of an external magnetic field, of variable intensity, in the
      direction parallel or transverse to the stripes. The different evolution of the
      modes with the external magnetic field is accompanied by a distinctive spatial
      localization in specific regions, such as the closure domains at the surface of
      the stripes and the bulk domains localized in the inner part of the stripes. The
      complementarity of BLS and FMR techniques, based on different selection rules, is
      found to be a fruitful tool for the study of the wealth of localized magnetic
      excitations generally found in nanostructures.

PMID- 29067918
TI  - A rare case of bullhorn-injury associated traumatic hernia of anterior abdominal
      wall managed by laparoscopic sutured tissue-only repair.
AB  - Traumatic abdominal wall hernias (TAWHs) are relatively uncommon entities. Common
      mechanisms that predispose to such hernias include motor vehicle accidents, seat
      belt injuries, fall from height, handlebar injuries, and bullfighting. Bullhorn
      injury leading to TAWHs is an uncommon mechanism. We report here one such patient
      who was managed by laparoscopic transperitoneal anatomical repair of the defect
      using polypropylene suture. The patient recovered well without any complication
      and is being followed up. Such small defects can be managed laparoscopically and
      tissue-only repair using a nonabsorbable suture is a feasible option. Our case is
      the first reported case of bullhorn-injury associated traumatic hernia managed
      laparoscopically and first reported case of TAWH in an adult which was managed by
      laparoscopic sutured tissue-only repair.

PMID- 29067919
TI  - Smoking and risk of colonic diverticulosis: A meta-analysis.
AB  - BACKGROUND/OBJECTIVES: The possible relationship between smoking and risk of
      colonic diverticulosis has been suggested by recent epidemiological studies,
      although the results were inconsistent. This meta-analysis was conducted to
      summarize all available data. METHODS: A comprehensive literature review was
      conducted using the MEDLINE and EMBASE databases through May 2017 to identify all
      studies that compared the risk of colonic diverticulosis among current and former
      smokers versus nonsmokers. Effect estimates from each study were extracted and
      combined together using the random-effect, generic inverse variance method of
      DerSimonian and Laird. RESULTS: Of 465 potentially eligible articles, three
      prospective cohort studies with 130,520 participants met the eligibility criteria
      and were included in the meta-analysis. The risk of colonic diverticulosis in
      current smokers was significantly higher than nonsmokers with the pooled risks
      ratio of 1.46 (95% confidence interval [CI], 1.13-1.89). However, the risk of
      colonic diverticulosis in former smokers was not significantly higher than
      nonsmokers with the pooled risk ratio of 1.13 (95% CI, 0.88-1.44). CONCLUSIONS: A
      significantly increased risk of colonic diverticulosis among current smokers is
      demonstrated in this study.

PMID- 29067920
TI  - Upper airway angioedema after topical hyaluronic acid in a patient treated with
      bisoprolol.

PMID- 29067922
TI  - Primary adrenal teratoma: An unusual tumor - Challenges in diagnosis and surgical
      management.
AB  - We report a rare case of a 25-year-old lady who presented with right
      hypochondriac pain associated with weakness for 3 months. Her hormonal evaluation
      was normal. Computed tomography scan revealed an adrenal mass for which a right
      open transperitoneal adrenalectomy was performed, and the lesion was diagnosed as
      mature teratoma on histopathological examination. Teratoma is an unusual neoplasm
      which arises from one or all the three germ layers. Extragonadal teratomas are
      rare in adults as compared to children and are mostly retroperitoneal in
      location, constituting only 4% of all primary teratomas. Primary adrenal
      teratomas are even rarer and to the best of our knowledge, only eight cases have
      been reported in adults in the past 10 years. Adrenal teratoma can pose a
      diagnostic challenge because radiologically it mimics myelolipoma,
      angiomyolipoma, liposarcoma, or pheochromocytoma. Mature teratomas are usually
      benign but may possess malignant potential, the chances of which are greater in
      adults as compared to children, making it an important entity requiring a proper
      diagnosis and management.

PMID- 29067921
TI  - Photokeratitis induced by ultraviolet radiation in travelers: A major health
      problem.
AB  - Ultraviolet (UV) irradiation is one of the several environmental hazards that may
      cause inflammatory reactions in ocular tissues, especially the cornea. One of the
      important factors that affect how much ultraviolet radiation (UVR) humans are
      exposed to is travel. Hence, traveling is considered to include a more acute UVR
      effect, and ophthalmologists frequently evaluate and manage the ocular
      manifestations of UV irradiation, including UV-induced keratitis. The purpose of
      this paper is to provide an evidence-based analysis of the clinical effect of UVR
      in ocular tissues. An extensive review of English literature was performed to
      gather all available articles from the National Library of Medicine PubMed
      database of the National Institute of Health, the Ovid MEDLINE database, Scopus,
      and ScienceDirect that had studied the effect of UVR on the eye and its
      complications, between January 1970 and June 2014. The results show that UVR at
      300 nm causes apoptosis in all three layers of the cornea and induces keratitis.
      Apoptosis in all layers of the cornea occurs 5 h after exposure. The effect of
      UVR intensity on the eye can be linked to numerous factors, including solar
      elevation, time of day, season, hemisphere, clouds and haze, atmospheric
      scattering, atmospheric ozone, latitude, altitude, longitudinal changes, climate,
      ground reflection, and geographic directions. The most important factor affecting
      UVR reaching the earth's surface is solar elevation. Currently, people do not
      have great concern over eye protection. The methods of protection against UVR
      include avoiding direct sunlight exposure, using UVR-blocking eyewear (sunglasses
      or contact lenses), and wearing hats. Hence, by identifying UVR intensity
      factors, eye protection factors, and public education, especially in travelers,
      methods for safe traveling can be identified.

PMID- 29067924
TI  - Assessment of healthcare measures, healthcare resource use, and cost of care
      among severe hemophilia A patients in Mumbai region of India.
AB  - Background: In India, the low public health priority given to rare disorders such
      as hemophilia hinders their management and optimal care, leading to relatively
      poor health outcomes. This study aims to profile the multidimensional health
      status of patients with severe hemophilia A, and its association with the use of
      healthcare resources and the cost of care in Mumbai region of India. Subjects and
      Methods: A cross-sectional, single-center study was conducted during January-May
      2011, among 160 patients diagnosed with severe hemophilia A in Mumbai region of
      India. Their health status was documented using the Hemophilia Utilization Group
      Study's validated instrument of Functional Health Status Measure (FHS) and a
      single item of Self-care Measure.  Results: Of 160 patients, 55% (n = 88) scored
      on the lower side on the FHS, with an average score of 6.65 +/- 2.85. The use of
      healthcare resources and cost of treatment were considerable for patients with a
      lower mean rank score on the FHS and a higher mean rank score on the self-care
      measure. The consumption of clotting factor concentrates (CFCs), number of visits
      to a health facility and incidence of inpatient episodes were significantly
      associated with a relatively low score on the FHS. Similarly, a higher cost of
      treatment, in terms of the cost of CFCs, direct cost, emergency room cost, and
      indirect cost, were significantly associated with a lower score on the FHS.
      Conclusion: The health status of patients with severe hemophilia A is compromised
      and has a significant impact on the use of healthcare resources and the cost of
      treatment.

PMID- 29067925
TI  - 3q26 chromosomal anomalies in acute myeloid leukemia: First descriptions from
      India.
AB  - Cytogenetic anomalies involving the 3q26 chromosomal region are rare in acute
      myeloid leukemia (AML). There is no such description of these anomalies from the
      Indian sub-continent. A total of 174 AML patients were admitted to our hospital
      for therapy between January 2001 and January 2008. Cytogenetic studies could be
      done in 115 patients; which revealed three cases with 3q26 anomalies. All were
      males. In the first two cases, the anomaly was detected in all the metaphases.
      The common features seen were the presence of only mild thrombocytopenia
      (relatively high platelet counts when assessed against the background of AML with
      high blast percentages), monosomy 7, myeloperoxidase positive blasts, mild
      eosinophilia, and poor therapeutic response. In the third case, the chromosome 3
      anomaly was present in only one metaphase. Such an anomaly has not been reported.
      Only the third patient responded to induction therapy but subsequently relapsed
      after being in complete remission for 15 months. 3q26 anomalies are associated
      with monosomy 7, relatively higher platelet counts at diagnosis as compared with
      other non-3q rearranged AML's and poor prognosis. The precise mechanisms
      underlying leukemogenesis need to be elucidated and better treatments devised
      since these patients respond poorly to therapy.

PMID- 29067926
TI  - Rare tracheal tumor: Solitary plasmacytoma.
AB  - Primary tracheal tumors are rare and trachea is an exceedingly rare site of
      extramedullary plasmacytoma (EMP). We report a case of solitary tracheal
      plasmacytoma causing symptoms of airway obstruction in a 59-year-old man.
      Flow/volume loop indicated the fixed central airway obstruction. Computerized
      tomography and bronchoscopy demonstrated a sessile tumor on posterior tracheal
      wall obstructing 80% of the lumen. Partial tracheal resection with T-T
      anastomosis was performed. Pathologic analysis of resected mass revealed EMP.
      Additional investigations excluded multiple myeloma. There are no signs of
      disease recurrence after 7-year follow-up.

PMID- 29067927
TI  - Observational study comparing pharmacoinvasive strategy with primary percutaneous
      coronary intervention in patients presenting with ST elevation myocardial
      infarction to a tertiary care centre in India.
AB  - Objective: The objective was to study whether the incidence of composite end
      points (mortality, cardiogenic shock and re-myocardial infarction [re-MI]) in
      pharmacoinvasive strategy was noninferior to primary percutaneous coronary
      intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).
      Methods: This was an observational study which included 138 patients. The study
      included patients admitted with a diagnosis of STEMI within 24 h of symptom
      onset, who underwent primary PCI or pharmacoinvasive therapy in a single center
      over a 9-month period. Primary end points (death within 30 days, re-MI within 30
      days, and cardiogenic shock) and secondary end points (arrhythmias, bleeding
      manifestations, ischemic stroke, ejection fraction, mechanical complications, and
      duration of hospital stay) were compared between the two groups at 1 month after
      intervention. Results: At one month follow-up, the incidence rate for primary end
      points was 5 events per 43 patients (11.6%) in pharmacoinvasive arm and 18 events
      per 95 patients (18.9%) in primary PCI arm, a difference of - 7.3% (95%
      confidence interval: 18.5, 7.1). This finding shows that pharmacoinvasive
      strategy as compared with primary PCI in the management of STEMI was equivalent
      in terms of composite primary outcome. There was no significant difference
      between the secondary outcomes between the two groups. Use of thrombus aspiration
      device and in turn the thrombus burden was significantly lower in the
      pharmacoinvasive arm. Conclusion: This observational study showed that
      pharmacoinvasive strategy was as good as primary PCI in STEMI, in our setting,
      where primary PCI may be delayed or not possible at all due to financial and
      logistic constraints.

PMID- 29067928
TI  - Multi-organ IgG4-related disease: Demystifying the diagnostic enigma.
AB  - IgG4-related disease (IgG4-RD) is a multisystemic mass forming immune-mediated
      disease entity, commonly creating confusion and diagnostic challenges. We present
      a case of a 25-year-old female who presented with bilateral orbital masses,
      lymphadenopathy, paraspinal and renal masses, which clinicoradiologically
      simulated lymphoma. The lymph node biopsy revealed interfollicular sheets of
      plasma cells creating confusion with Castleman's disease and marginal zone
      lymphoma. The orbital biopsy revealed ductular destruction, periductular plasma
      cells, and fibrosis, mimicking Sjogren's syndrome and Castleman's disease.
      However, the correlation of the clinical features with histopathological
      findings, IgG4 immunopositivity, and serum studies helped in clinching the
      diagnosis. This case presents an uncommon combination of clinical features
      infrequently reported in literature. Furthermore, and more importantly, it
      highlights the need to keep a differential of IgG4-RD in mind, to aid early and
      correct treatment of the disease.

PMID- 29067929
TI  - Comparison of stress and burnout among anesthesia and surgical residents in a
      tertiary care teaching hospital in North India.
AB  - Objective: The residents undergoing training at hospitals in our country face
      challenges in terms of infrastructure and high workload with undefined working
      hours. The aim of the study was to compare the stress and burnout levels in
      trainee doctors doing residency in surgical fields and anesthesia at a tertiary
      care academic center in North India. Materials and Methods: A comparative,
      observational study was conducted in a tertiary care teaching hospital in North
      India. After Ethics Committee approval, 200 residents (100 each from surgical
      branches and anesthesia) were required to fill a questionnaire with information
      about age, sex, year of residency, marital status, and the Perceived Stress Scale
      10, and Burnout Clinical Subtype Questionnaire-12. Burnout and perceived stress
      were compared between residents of anesthesia and surgical specialties. Results:
      Residents of both surgical and anesthesia branches scored high in perceived
      stress, namely 21 and 18, respectively. The score was significantly higher in
      surgical residents (P = 0.03) and increased progressively with the year of
      residency. The majority of residents (90% surgical, 80% anesthesia) felt that
      they were being overloaded with work. However, only 20%-30% of respondents felt
      that there was lack of development of individual skills and still fewer (<10%)
      reported giving up in view of difficulties. Conclusion: There is high level of
      stress and overload dimension of burnout among the residents of anesthesia and
      surgical branches at our tertiary care academic institution and the surgical
      residents score marginally higher than anesthesia residents.

PMID- 29067930
TI  - Granulomatous slack skin syndrome: Report of a unique case.
AB  - Granulomatous slack skin syndrome is a rare variant of cutaneous T-cell lymphoma
      (mycosis fungoides). It is characterized clinically by redundant skin folds,
      which show a predilection towards flexural areas such as the axilla and the
      groin. Histologically, it shows a granulomatous T-cell infiltrate and loss of
      elastic tissue. It has an indolent but progressive course; and is usually
      refractory to treatment. We report a unique case of slack skin syndrome, sparing
      the classical sites with rapid and unusual involvement of non-intertriginous
      areas.

PMID- 29067931
TI  - Painful ulcer of the pinna in an immunocompromised patient.

PMID- 29067932
TI  - An unusual case of lymphomatoid papulosis type E with extensive necrosis.
AB  - Lymphomatoid papulosis type E (LyP) is a recently described subtype of LyP
      characterized by an angioinvasive infiltrate of atypical lymphocytes expressing
      CD30. We present a case of type E LyP with extensive cutaneous necrosis in the
      histopathological evaluation which was misdiagnosed as an ulcerative form of
      bacterial skin infection. The remarkable cutaneous necrosis showed in our case
      might be related to the angiodestructive infiltrate that was present in this
      circumstance.

PMID- 29067933
TI  - Polymorphism of glutathione S-transferase M1 and T1 genes and susceptibility to
      psoriasis disease: A study from North India.
AB  - BACKGROUND: Increased oxidative stress and resulting inflammation has been
      emphasized as a factor in the pathogenesis of many diseases including psoriasis.
      Glutathione S-transferases (GSTs) protect against oxidative stress, inflammation,
      and genotoxicity. Polymorphisms in the GST genes may lead to an imbalance in pro-
      and antioxidant systems resulting in the increased production of reactive oxygen
      species that could influence the pathogenesis of psoriasis. AIM: The aim of this
      study was to investigate the association between GSTs (GSTM1 and GSTT1) gene
      polymorphism in patients with chronic plaque psoriasis as a factor in the
      susceptibility and development of psoriasis. MATERIALS AND METHODS: We assessed
      128 patients with psoriasis and 250 age- and sex-matched healthy controls.
      Genomic DNA was extracted from peripheral blood by the phenol chloroform method.
      The null GSTT1 and GSTM1 genotypes were identified by multiplex polymerase chain
      reaction (PCR) method. RESULTS: The null genotype of GSTM1 and GSTT1 was seen in
      45.3% and 40.6% in psoriasis patients whereas in the controls it was 34.4% and
      20.0%, respectively. A significant association was seen between the null alleles
      of the GSTT1 (OR = 2.74) and GSTM1 (OR = 1.58) alone or in combination with
      tobacco use (P < 0.001) and psoriasis risk. The presence of both null genotypes
      of GSTM1 and GSTT1 further increased the risk of psoriasis (OR = 3.52) when
      compared with the positive genotypes of GSTM1 and GSTT1. LIMITATIONS: A major
      limitation of this study was the small sample size. A large epidemiological study
      is necessary to confirm these findings. CONCLUSIONS: The null genotype of GSTT1
      is a strong predisposing factor for psoriasis in North India.

PMID- 29067934
TI  - Prevalence of ocular findings in a sample of Egyptian patients with psoriasis.
AB  - BACKGROUND: Psoriasis is a common disorder worldwide. The prevalence of psoriasis
      in Egypt, an African country with a Caucasian population, ranges 0.19-3%. Despite
      this relatively high prevalence of psoriasis, there are no epidemiologic data
      regarding the burden of associated eye affection. Determining the magnitude of
      the problem could help in offering better integrated health services. AIM: The
      purpose of this study was to evaluate eye involvement in a sample of Egyptian
      psoriatic patients. PATIENTS AND METHODS: This case-control study included 100
      patients with psoriasis and 100 age and sex matched healthy controls. Psoriasis
      extent and severity was graded by psoriasis area and severity index (PASI).
      Complete ophthalmological examination and tests for dry eye were performed to all
      subjects. RESULTS: The mean age of the psoriasis group was 50.7 +/- 14.3 years.
      Thirty eight percent of the cases were females. The mean duration of psoriasis
      was 10.1 +/- 7.5 years. Psoriasis patients had more conjunctival injection (n =
      40, P = 0.035), more pinguecula (n = 38, P = 0.048) than controls. Ocular surface
      disease index (OSDI), tear breakup time (TBUT), Schirmer I, and Rose Bengal
      staining showed statistically significant positive results in the psoriasis
      group. CONCLUSION: This is the first report on the prevalence of eye
      comorbidities in Egyptian psoriatic patients. Dry eyes were more common with
      psoriasis, particularly the erythrodermic type. Other ocular findings were not
      statistically significantly different except for conjunctival injection and
      pinguecula.

PMID- 29067935
TI  - Identification of a novel missense mutation in the NOD2 gene in a Chinese child
      with early-onset sarcoidosis.

PMID- 29067936
TI  - Congenital asymptomatic papule on the lower eyelid.

PMID- 29067937
TI  - Subfascial Endoscopic Perforator Surgery: A safe and novel minimal invasive
      procedure in treating varicose veins in 2nd trimester of pregnancy for below knee
      perforator incompetence.
AB  - Aim: : Aim of this study is to evaluate the results of Subfascial Endoscopic
      Perforator Surgery(SEPS) in treating varicose veins in 2nd trimester of pregnancy
      for below knee perforator incompetence. Materials and Methods: A case series was
      undertaken at our institute from the period January 2010 to January 2014 on 45
      pregnant women. Pregnant women with failed conservative management for varicose
      veins were subjected to SEPS in 2nd trimester Perioperative parameters like
      operative time, intraoperative complications, post-operative complications,
      hospital stay, pain relief, ulcer healing duration and recurrence rate were
      studied. All the patients were reviewed and followed up for a minimum period of 3
      years. Results: During the study period.total of 45 pregnant women were enrolled
      in the study. The median age of the patients was 26 years (range 22 years - 30
      years). The mean operative time was 90+/-10 minutes. The post-operative hospital
      stay was 1-2days. There were no intraoperative complications like bleeding or gas
      embolism. There were no post-operative complications like seroma or abscess, port
      site infection, deep vein thrombosis and gas embolism. Mean healing duration of
      ulcers following surgery was 7-8 weeks.No patient complained of temporary or
      permanent paraesthesia. Every patient was subjected to follow up for a minimum
      period of 3 years. 5(11.1%) patients with recurrence were documented in the
      study. Conclusion: SEPS is a safe, cost effective and novel minimal invasive
      procedure in treatment of varicose veins in 2nd trimester of pregnancy for below
      knee perforator incompetence.

PMID- 29067938
TI  - Laparoscopic Roux-en-Y gastric bypass: Outcomes of a case-matched comparison of
      primary versus revisional surgery.
AB  - INTRODUCTION: Laparoscopic adjustable gastric banding and laparoscopic sleeve
      gastrectomy are popular bariatric procedures. Certain complications may
      necessitate revision. Adverse outcomes are reported after revisional bariatric
      surgery. We compared patients undergoing revisional versus primary laparoscopic
      Roux-en-Y gastric bypass (LRYGB). MATERIALS AND METHODS: This was retrospective
      comparative 1:1 case-matched analysis of revisional LRYGB Group A versus primary
      LRYGB (pLRYGB/Group B). Matching was based on body mass index (BMI) and
      comorbidities. BMI decrease at 6 and 12 months post-surgery, comorbidity
      resolution, operative time, morbidity and length of hospital stay (LOS) were
      compared. Total decrease in BMI, i.e., change from before initial bariatric
      procedure to 12 months after revision for Group A was also compared. RESULTS:
      Median BMI (inter-quartile range) for Group A decreased to 44.74 (7.09) and 41.49
      (6.26) at 6 and 12 months, respectively, for Group B corresponding figures were
      38.74 (6.9) and 33.79 (6.64) (P = 0.001 and P = 0.0001, respectively). Total
      decrease in BMI (Group A) was 9.8, whereas BMI decrease at 12 months for Group B
      was 15.2 (P = 0.23). Hypertension resolved in 63% (Group A), 70% (Group B) (P =
      0.6). Diabetes resolution was 80% (Group A), 63% (Group B) (P = 0.8). Operative
      time for Groups A, B was 151 +/- 17, 137 +/- 11 min, respectively (P = 0.004).
      There was no difference in morbidity and LOS. CONCLUSION: Comorbidity resolution
      after revisional and pLRYGB are similar. Less weight loss is achieved after
      revision than after pLRYGB, but total weight loss is comparable. Revisional
      surgery is safe when performed by experienced surgeons in high-volume centres.

PMID- 29067939
TI  - A case of total laparoscopic sigmoidectomy involving the use of needle forceps
      and transanal specimen extraction for sigmoid colon cancer.
AB  - A 76-year-old male underwent endoscopic mucosal resection for a stage T1 tumour
      of the sigmoid colon. We performed laparoscopic sigmoidectomy through 5 ports
      using needlescopic instruments. The resected specimen was extracted from the
      abdominal cavity transanally. After attaching an anvil to the sigmoidal stump,
      the rectal stump was reclosed using an endoscopic linear stapler, and then,
      colorectal anastomosis was conducted using the double stapling technique.
      Performing transanal specimen extraction using needlescopic forceps improves
      aesthetic outcomes and reduces post-operative pain and the risk of abdominal
      incisional hernias. This method is an easy to introduce a form of reduced-port
      surgery because of its feasibility and conventional port arrangement. Hence, we
      consider that it is an option for minimally invasive surgery.

PMID- 29067940
TI  - A case report of cardia cancer complicated with idiopathic muscular hypertrophy
      of the oesophagus treated with thoracoscopic surgery.
AB  - The incidence of idiopathic muscular hypertrophy of oesophagus (IMHE) is low, and
      <100 cases of IMHE have been reported. IMHE is a benign oesophageal disease,
      characterised by hyperplasia of all layers of the wall and in particular, muscle
      layer. Only a few cases have been reported regarding its clinical symptoms and
      images. In this present case, we report a cardia cancer with IMHE, showing
      significant hypertrophy of muscular layer of middle part of the oesophagus and
      successfully treated with minimally invasive thoracoscopic surgery.

PMID- 29067941
TI  - Acute pancreatitis as an unusual early post-operative complication following
      laparoscopic sleeve gastrectomy.
AB  - Laparoscopic sleeve gastrectomy (LSG) at present one of the most commonly
      performed surgical treatments for morbid obesity worldwide. There are some
      complications regarding this procedure in the literature. This report presents a
      patient who developed acute pancreatitis immediate post-LSG. Patient was referred
      to our institute on 10th post-operative day with a complaint of fever, nausea,
      abdominal pain and leucocytosis. A diagnostic laparoscopy showed pancreatitis.
      Post-operatively, the patient was managed on treatment line of acute pancreatitis
      and recovered well. LSG is a common procedure in bariatric, and the most common
      complications are leakage and bleeding from the suture line. However, we
      encountered pancreatitis after LSG which is a rarely reported complication after
      LSG. We hypothesise that the development of acute pancreatitis in patients
      undergoing LSG is not well recognised and reported.

PMID- 29067942
TI  - Primary leiomyosarcoma of the inferior vena cava.

PMID- 29067943
TI  - Transoral endoscopic total thyroidectomy vestibular approach: A case series and
      literature review.
AB  - Conventional open thyroidectomy is often associated with post-operative
      complications including nerve damage, voice disturbances, paraesthesias,
      adhesions and prominent scarring. Several endoscopic surgical techniques have
      been reported as alternatives to conventional thyroidectomy. Natural orifice
      transluminal endoscopic surgery is a promising approach which leaves no scar,
      produces few complications and affords faster discharge from care. Several
      studies have explored its utility in total thyroidectomy in patients with benign
      or malignant thyroid disease. Herein, we present a case series on the successful
      application of transoral endoscopic total thyroidectomy vestibular approach
      (TOETVA) in benign and malignant diseases of the thyroid. We performed TOETVA in
      11 patients presenting with benign or malignant thyroid nodules in our hospital,
      between 1st January 2015 and 30th June 2016. The surgery was completed
      successfully in all patients with a pre-operative diagnosis of multinodular
      goitre. The surgery was performed under general anaesthesia and the mean
      operative time was 130 min. The mean blood loss was 2-3 cc. No incidence of
      recurrent laryngeal nerve injury, damage to mental nerve, parathyroid damage or
      peri-incisional adhesion occurred in the study participants. No visible scarring
      occurred in the patients following surgery. The patients had an uneventful
      recovery after the surgery and were discharged after 4 days. TOETVA is safe and
      effective in the surgical management of multinodular goitre and offers a scar
      free alternative to conventional surgery.

PMID- 29067944
TI  - Stomach resection with intraoperative fluoroscopy in laparoscopic distal
      gastrectomy for early gastric cancer.
AB  - Background: In Japan, laparoscopic distal gastrectomy (LDG) is common for early
      gastric cancer. Formerly, we used to verify the location of the marking clip to
      decide the proximal incisional line with our hand, through a small epigastric
      incision. In 2015, we introduced intracorporeal reconstruction and started to
      decide the incisional line using intraoperative fluoroscopy. Herein, we aimed to
      evaluate the efficacy and safety of intraoperative fluoroscopy in LDG. Patients
      and Methods: : A total of 19 patients were included in this retrospective
      observational study. On the day before operation, we endoscopically clipped
      several points located 2 cm proximal to the tumour edge to cover about half of
      the tumour. After lymph node dissection, we incised the stomach with an
      endoscopic linear stapling device, including the previously placed clips, guided
      by intraoperative fluoroscopy. Reconstruction was performed in all patients who
      underwent Billroth I and Roux-en-Y procedures. Results: No complications were
      observed during pre-operative endoscopic clipping or intraoperatively. On
      pathological examination, all resected specimens had negative margins, and the
      mean distance from the tumour edge was 28.5 +/- 16.5 (13-60) mm. Conclusion:
      Stomach resection with intraoperative fluoroscopic guidance was safe and
      effective.

PMID- 29067945
TI  - Post-cholecystectomy syndrome: A new look at an old problem.
AB  - Background: Despite being the most commonly performed operations, sometimes
      cholecystectomy fails to relieve symptoms; this is now a well-recognised clinical
      entity termed 'post-cholecystectomy syndrome' (PCS). Very few studies from India
      deal with PCS, and the present study was carried out to find the incidence and
      risk factors for PCS in patients undergoing elective laparoscopic cholecystectomy
      (LC). Materials and Methods: The records of 207 patients undergoing elective LC
      were prospectively maintained for 6 months after surgery. Persistence or
      appearance of new symptoms after surgery was documented and investigated only
      when they persisted beyond 30 days of surgery. Results: There were 185 (89.4%)
      female patients and 22 (10.6%) male patients with a mean age of 44.4 years (age
      range: 12-79 years). Conversion to open cholecystectomy was done in 18 patients
      (8.69%), mainly due to adhesions and unclear anatomy. The incidence of symptoms
      was found to be 13% at 6 months follow-up, showing a reducing trend from 58% in
      the 1st week after LC; the most common symptom in symptomatic patients was
      dyspepsia (55.56%). On investigation, a cause for symptoms could be detected in
      only 0.97%. Conclusion: Symptoms are common after LC, but they settle over time.
      Very few patients have a detectable cause for symptoms after LC, and it is
      difficult to predict which patients will become symptomatic after LC; in the
      present series, previous attacks of cholecystitis and presence of co-morbid
      conditions were the only consistent risk factors for symptoms after LC.

PMID- 29067947
TI  - Laparoscopic management of massive intraperitoneal haemorrhage caused by an acute
      gallbladder perforation.
AB  - Laparoscopic cholecystectomy is the gold standard for managing the treatment of
      patients with symptomatic gallstone disease. Certain patients with acute
      cholecystitis will develop gallbladder perforation (GP). Furthermore, massive
      intraperitoneal haemorrhage following perforation is a rare complication. The
      high morbidity and mortality rates associated with this condition are due to
      delays in the diagnosis and treatment since signs and symptoms of perforation do
      not differ significantly from those of uncomplicated cholecystitis. Severe
      inflammation and haemodynamic instability necessitate exploratory laparotomy in
      many patients. To the best of our knowledge, no study had described laparoscopic
      completion cholecystectomy for massive intraperitoneal haemorrhage caused by an
      acute GP. Laparoscopy can be an option for the management of these patients, in
      selected cases and with available expertise.

PMID- 29067946
TI  - Can post-operative antibiotic prophylaxis following elective laparoscopic
      cholecystectomy be completely done away with in the Indian setting? A prospective
      randomised study.
AB  - Premise and Objective: : Elective laparoscopic cholecystectomy (LC) has low risk
      for post-operative infectious complications; still most clinicians use persistent
      post-operative prophylactic antibiotics out of habit, tradition, or simply as
      defensive practice due to evolving medicolegal implications of a large number of
      surgeries being showcased as daycare or next day discharge procedures. This
      randomised prospective trial was done to test the need for such prophylaxis in
      cases of elective LC in a rural/semi-urban setting. Materials and Methods: : Two
      hundred and ten successive patients undergoing elective LC were randomised into
      groups receiving single dose of injection ceftriaxone at the time of induction of
      anaesthesia, (Group A = 112 cases) and those who in addition to above received
      injection ceftriaxone twice daily for 2 days postoperatively (Group B = 98
      cases). Post-operative infectious complications between two groups were compared
      for variables such as age, sex, body mass index and bile/stone spillage. Results:
      : There was no significant difference in surgical site infection rates between
      the groups for variables such as age, sex, body mass index, duration of symptoms,
      American Society of Anesthesiologists grade, duration of surgery and hospital
      stay. Intraoperative spillage of stones (9.8% [A]: 5.1% [B]) did not increase
      infectious complications even in the presence of positive bile culture (Group A,
      N = 7 vs. Group B, N = 3). An operative time of greater than 60 min was found to
      be associated with increased surgical site infection (P = 0. 0006). Conclusion: :
      Single dose of ceftriaxone at the time of induction is adequate prophylaxis
      following elective LC even in the rural/semi-urban Indian setting and routine
      continued administration of antibiotic should be abandoned as it contributes to
      adverse reactions, drug resistance and unnecessary financial burden.

PMID- 29067948
TI  - Scoliosis in China: History and Present Status.

PMID- 29067949
TI  - Joint Registration System under the Background of Big Data.

PMID- 29067950
TI  - Percutaneous Sacroiliac Screw Placement: A Prospective Randomized Comparison of
      Robot-assisted Navigation Procedures with a Conventional Technique.
AB  - BACKGROUND: Sacroiliac (SI) screw fixation is a demanding technique, with a high
      rate of screw malposition due to the complex pelvic anatomy. TiRobotTM is an
      orthopedic surgery robot which can be used for SI screw fixation. This study
      aimed to evaluate the accuracy of robot-assisted placement of SI screws compared
      with a freehand technique. METHODS: Thirty patients requiring posterior pelvic
      ring stabilization were randomized to receive freehand or robot-assisted SI screw
      fixation, between January 2016 and June 2016 at Beijing Jishuitan Hospital. Forty
      five screws were placed at levels S1 and S2. In both methods, the primary end
      point screw position was assessed and classified using postoperative computed
      tomography. Fisher's exact probability test was used to analyze the screws'
      positions. Secondary end points, such as duration of trajectory planning,
      surgical time after reduction of the pelvis, insertion time for guide wire,
      number of guide wire attempts, and radiation exposure without pelvic reduction,
      were also assessed. RESULTS: Twenty-three screws were placed in the robot
      assisted group and 22 screws in the freehand group; no postoperative
      complications or revisions were reported. The excellent and good rate of screw
      placement was 100% in the robot-assisted group and 95% in the freehand group. The
      P value (0.009) showed the same superiority in screw distribution. The
      fluoroscopy time after pelvic reduction in the robot-assisted group was
      significantly shorter than that in the freehand group (median [Q1, Q3]: 6.0 [6.0,
      9.0] s vs. median [Q1, Q3]: 36.0 [21.5, 48.0] s; chi2 = 13.590, respectively, P <
      0.001); no difference in operation time after reduction of the pelvis was noted
      (chi2 = 1.990, P = 0.158). Time for guide wire insertion was significantly
      shorter for the robot-assisted group than that for the freehand group (median
      [Q1, Q3]: 2.0 [2.0, 2.7] min vs. median [Q1, Q3]: 19.0 [15.5, 45.0] min; chi2 =
      20.952, respectively, P < 0.001). The number of guide wire attempts in the robot
      assisted group was significantly less than that in the freehand group (median
      [Q1, Q3]: 1.0 [1.0,1.0] time vs. median [Q1, Q3]: 7.0 [1.0, 9.0] times; chi2 =
      15.771, respectively, P < 0.001). The instrumented SI levels did not differ
      between both groups (from S1 to S2, chi2 = 4.760, P = 0.093). CONCLUSIONS:
      Accuracy of the robot-assisted technique was superior to that of the freehand
      technique. Robot-assisted navigation is safe for unstable posterior pelvic ring
      stabilization, especially in S1, but also in S2. SI screw insertion with robot
      assisted navigation is clinically feasible.

PMID- 29067951
TI  - Radiological Analysis of Thoracolumbar Junctional Degenerative Kyphosis in
      Patients with Lumbar Degenerative Kyphosis.
AB  - BACKGROUND: Thoracolumbar junction (TLJ) is the transitional area between the
      lower thoracic spine and the upper lumbar spine. Vertebral compression fractures
      and proximal junctional kyphosis following spine surgery often occur in this
      area. Therefore, the study of development and mechanisms of thoracolumbar
      junctional degeneration is important for planning surgical management. This study
      aimed to review radiological parameters of thoracolumbar junctional degenerative
      kyphosis (TLJDK) in patients with lumbar degenerative kyphosis and to analyze
      compensatory mechanisms of sagittal balance. METHODS: From January 2016 to March
      2017, patients with lumbar degenerative kyphosis were enrolled in this
      radiographic study. Patients were divided into two groups according to
      thoracolumbar junctional angle (TLJA): the non-TLJDK (NTLJDK) group (TLJA <10
      degrees ) and the TLJDK group (TLJA >=10 degrees ). Complete spinopelvic
      radiographic parameters were analyzed and compared between two groups. Pearson or
      Spearman correlation coefficients and independent two-sample t-test or Mann
      Whitney U-test were used. RESULTS: A total of 77 patients with symptomatic
      sagittal imbalance due to lumbar degenerative kyphosis were enrolled in this
      study. There were 34 patients in NTLJDK group (TLJA <10 degrees ) and 43 patients
      in TLJDK group (TLJA >=10 degrees ). The median angle of lumbar lordosis (LL) in
      the NTLJDK or TLJDK groups was 23.40 degrees  (18.50 degrees , 29.48 degrees ) or
      19.50 degrees  (13.30 degrees , 24.55 degrees ), respectively. The median TLJAs
      in all patients and both groups were -11.20 degrees  (-14.60 degrees , -4.80
      degrees ), -3.70 degrees  (-7.53 degrees , -1.73 degrees ), and -14.30 degrees  (
      17.45 degrees , -13.00 degrees ), respectively. In the NTLJDK group, LL was
      correlated with thoracic kyphosis (TK; r = -0.400, P = 0.019), sacral slope (SS;
      r = 0.681, P < 0.001), and C7-sagittal vertical axis (r = -0.402, P = 0.018). In
      the TLJDK group, LL was correlated with TK (r = -0.345, P = 0.024), SS (r =
      0.595, P < 0.001), and pelvic tilt (r = -0.363, P = 0.017). There were
      significant differences in LL, TLJA, TK, SS, and pelvic incidence (PI) between
      two groups. CONCLUSIONS: Although TLJDK is common in patients with lumbar
      degenerative kyphosis, it might be generated by special characteristics of
      morphology and biomechanics of the TLJ. To maintain sagittal balance, pelvis back
      tilt might be more important in patients with TLJDK, whereas thoracic curve
      changes might be more important in patients without TLJDK.

PMID- 29067952
TI  - How to Fill the Cavity after Curettage of Giant Cell Tumors around the Knee? A
      Multicenter Analysis.
AB  - BACKGROUND: Intralesional excision with curettage is the standard method of giant
      cell tumor (GCT) treatment, but the ideal filling material after curettage
      remains controversial. The purpose of this study was to compare the oncological
      and functional outcomes which underwent cementation or bone grafting after GCT
      curettage around the knee. METHODS: We reported 136 cases with GCTs in distal
      femur or proximal tibia who accepted curettage from five clinical centers during
      the last 15 years. All patients were divided into two groups according to filling
      materials. Recurrence-free survival proportions were used to evaluate oncological
      outcomes while the Musculoskeletal Tumor Society (MSTS) 93 functional score was
      used to evaluate functional outcomes. Other parameters including surgical
      complication, general condition, and radiological classification had been
      analyzed. The valid statisitical data was analyzed using SPSS 13.0 software.
      RESULTS: After GCT curettage, 86 patients (63.2%) accepted bone grafting while 50
      patients (36.8%) accepted cementation. There was no statistical difference in
      age, gender, tumor location, radiological classification, fixation, follow-up
      time, and MSTS 93 functional score between cementation group and bone grafting
      group. The recurrence-free survival proportions showed that the recurrence rate
      in bone grafting group was higher than it in cementation group (P = 0.034).
      Surgical complication was lower in cementation group than that in bone grafting
      group but without statistically significant difference (P = 0.141). CONCLUSIONS:
      Parameters including patients' age, gender, tumor location, and radiological
      classification did not affect surgeons' treatments in cavity filling after GCT
      curettage. Cementation should be recommended because of easy usage, the similar
      postoperative knee function with bone grafting, and the better local tumor
      control than bone grafting.

PMID- 29067953
TI  - Magnetic Resonance Imaging for the Assessment of Long Bone Tumors.
AB  - BACKGROUND: Wide resection margins of osseous tumors are associated with a low
      incidence of local recurrence, making accurate measurement of the intraosseous
      extent of primary malignant long bone tumors is crucial. We compared the
      intraosseous tumor extent assessed by magnetic resonance imaging (MRI) with the
      gross specimen to evaluate the accuracy of MRI. METHODS: A total of 255 patients
      with primary malignant tumors in the long bones were included. Using MRI, we
      defined the length of tumor as the distance from the articular surface to the
      boundary between abnormal and normal marrow signal. The extent of the abnormal
      intraosseous signal was measured on unenhanced T1-weighted (T1WI) magnetic
      resonance images after chemotherapy. All gross surgical specimens were sectioned,
      and tumor extent was measured. Wilcoxon signed-rank test was used to test the
      differences between MRI and gross specimen findings. Spearman's correlation
      analysis was used to test the correlation between groups. RESULTS: Median tumor
      length by gross specimen (112 mm; range, 45-300 mm) was longer than that by MRI
      (108 mm; range, 45-304 mm; Z = -6.916, P < 0.001). Of 255 images, tumor length
      was accurately represented on 27 T1WI magnetic resonance images, overestimated on
      79 images, and underestimated on 149 images. The median difference between
      imaging and gross specimen measurements was 2.0 mm (range: 1.0-15.0 mm) for the
      79 cases where tumor length was overestimated, and 5.0 mm (range: 1.0-18.0 mm)
      for the 149 cases where tumor length was underestimated. The Spearman correlation
      demonstrated a high correlation of tumor length on gross specimen with the tumor
      length on MRI (R = 0.99, P < 0.01). CONCLUSIONS: We conclude that preoperative
      MRI could be a useful method in determining intramedullary malignant bone tumor
      boundaries and may serve as an accepted assessment method of long bone tumors
      before limb-sparing surgery.

PMID- 29067954
TI  - Radiographic Measurement of Femoral Lateral Bowing and Distal Femoral Condyle
      Resection Thickness: Variances and Effects on Total Knee Arthroplasty Planning.
AB  - BACKGROUND: Accurate evaluation of the plain radiography of lower limb is
      critical for preoperative planning of total knee arthroplasty (TKA). We aimed to
      investigate the effect of femoral lateral bowing and rotation on the radiographic
      measurements of distal femoral condyle resection thickness (DRT) and the distal
      femoral resection valgus angle (FVA). METHODS: We analyzed 246 three-dimensional
      femoral models generated from computed tomography images of 123 patients,
      acquiring projected contours in seven positions - 20 degrees  and 10 degrees 
      internal rotation; 0 degrees  rotation; 10 degrees , 20 degrees , 30 degrees ,
      and 40 degrees  external rotation - for each model. Medial and lateral condyle
      DRTs, femoral shaft lateral bowing angle (FBA), and distal FVA were determined
      for each position. Linear mixed effect model was used to determine the effect of
      degree of femur rotation on repeated measurements of DRT or FVA. RESULTS: FBA
      significantly affected the FVA and DRT (Pearson's R = 0.767 and -0.408,
      respectively; P < 0.000). Samples were divided into three groups according to the
      FBA measured in neutral position: FBA <0 degrees : DRT 3.75 +/- 1.30 mm, FVA 4.53
      degrees  +/- 1.27 degrees ; FBA >0 degrees  but <3 degrees : DRT 3.39 +/- 1.31
      mm, FVA 5.92 degrees  +/- 1.31 degrees ; FBA >3 degrees : DRT 2.22 +/- 1.31 mm,
      FVA 7.37 degrees  +/- 1.31 degrees . From simulated 20 degrees  internal rotation
      to 40 degrees  external rotation in each femoral model, the average variation
      ranges of radiographically measured DRT, FVA, and FBA were 0.50 +/- 0.28 mm, 2.93
      degrees  +/- 0.96 degrees , and 10.33 degrees  +/- 1.90 degrees , respectively,
      with no significant differences among the FBA groups. The degree of femoral
      rotation significantly affected the FVA (F = 62.148, P < 0.000), whereas there
      was no effect on condyle resection thickness (F = 0.4705, P = 0.494).
      CONCLUSIONS: Axial femoral rotation has less effect on radiographic measurements
      of differences in the DRT than on those of the distal FVA.

PMID- 29067955
TI  - Effects of Lower Limb Alignment and Tibial Component Inclination on the
      Biomechanics of Lateral Compartment in Unicompartmental Knee Arthroplasty.
AB  - BACKGROUND: Lateral compartmental osteoarthritis (LCOA), a major complication
      after medial mobile-bearing unicompartmental knee arthroplasty (UKA), is highly
      associated with the increased stress of the lateral compartment. This study aimed
      to analyze the effects on the stress and load distribution of the lateral
      compartment induced by lower limb alignment and coronal inclination of the tibial
      component in UKA through a finite element analysis. METHODS: Eight three
      dimensional models were constructed based on a validated model for analyzing the
      biomechanical effects of implantation parameters on the lateral compartment after
      medial Oxford UKA: postoperative lower limb alignment of 3 degrees  valgus,
      neutral and 3 degrees  varus, and the inclination of tibial components placed in
      4 degrees , 2 degrees  valgus, square, and 2 degrees  and 4 degrees  varus. The
      contact stress of femoral and tibial cartilage and load distribution were
      calculated for all models. RESULTS: In the 3 degrees  valgus lower limb alignment
      model, the contact stress of femoral (3.38 MPa) and tibial (3.50 MPa) cartilage
      as well as load percentage (45.78%) was highest compared to any other model, and
      was increased by 36.75%, 47.70%, and 27.63%, respectively when compared to 3
      degrees  varus. In the condition of a neutral position, the outcome was
      comparable for the different tibial tray inclination models. The inclination did
      not greatly affect the lateral compartmental stress and load distribution.
      CONCLUSIONS: This study suggested that slightly varus (undercorrection) lower
      limb alignment might be a way to prevent LCOA in medial mobile-bearing UKA.
      However, the inclination (4 degrees  varus to 4 degrees  valgus) of the tibial
      component in the coronal plane would not be a risk factor for LCOA in neutral
      position.

PMID- 29067956
TI  - Significance of Lateral Pillar in Osteonecrosis of Femoral Head: A Finite Element
      Analysis.
AB  - BACKGROUND: The lateral pillar of the femoral head is an important site for
      disease development such as osteonecrosis of the femoral head. The femoral head
      consists of medial, central, and lateral pillars. This study aimed to determine
      the biomechanical effects of early osteonecrosis in pillars of the femoral head
      via a finite element (FE) analysis. METHODS: A three-dimensional FE model of the
      intact hip joint was constructed from the image data of a healthy control.
      Further, a set of six early osteonecrosis models was developed based on the three
      pillar classification. The von Mises stress and surface displacements were
      calculated for all models. RESULTS: The peak values of von Mises stress in the
      cortical and cancellous bones of normal model were 6.41 MPa and 0.49 MPa,
      respectively. In models with necrotic lesions in the cortical and cancellous
      bones, the von Mises stress and displacement of lateral pillar showed significant
      variability: the stress of cortical bone decreased from 6.41 MPa to 1.51 MPa
      (76.0% reduction), while cancellous bone showed an increase from 0.49 MPa to 1.28
      MPa (159.0% increase); surface displacements of cortical and cancellous bones
      increased from 52.4 MUm and 52.1 MUm to 67.9 MUm (29.5%) and 61.9 MUm (18.8%),
      respectively. In addition, osteonecrosis affected not only pillars but also
      adjacent structures in terms of the von Mises stress and surface displacement
      levels. CONCLUSIONS: This study suggested that the early-stage necrosis in the
      femoral head could increase the risk of collapse, especially in lateral pillar.
      On the other hand, the cortical part of lateral pillar was found to be the main
      biomechanical support of femoral head.

PMID- 29067957
TI  - Hepatic Cyp1a2 Expression Reduction during Inflammation Elicited in a Rat Model
      of Intermittent Hypoxia.
AB  - BACKGROUND: Intermittent hypoxia (IH) is a key element of obstructive sleep apnea
      (OSA) that can lead to disorders in the liver. In this study, IH was established
      in a rat model to examine its effects on the expression of hepatic cytochrome
      P450 (CYP) and CYP regulators, including nuclear receptors. METHODS: Hematoxylin
      and eosin staining was conducted to analyze the general pathology of the liver of
      rats exposed to IH. The messenger RNA (mRNA) expression levels of inflammatory
      cytokines, CYPs, nuclear factor-kappaB (NF-kappaB), and nuclear factors in the
      liver were measured by quantitative reverse transcription polymerase chain
      reaction. RESULTS: We found inflammatory infiltrates in the liver of rats exposed
      to IH. The mRNA expression level of interleukin-1beta was increased in the liver
      of the IH-exposed rats (0.005 +/- 0.001 vs. 0.038 +/- 0.008, P = 0.042), whereas
      the mRNA expression level of Cyp1a2 was downregulated (0.022 +/- 0.002 vs. 0.0050
      +/- 0.0002, P = 0.029). The hepatic level of transcription factor NF-kappaB was
      also reduced in the IH group relative to that in the control group, but the
      difference was not statistically significant and was parallel to the expression
      of the pregnane X receptor and constitutive androstane receptor. However, the
      decreased expression of the glucocorticoid receptor upon IH treatment was
      statistically significant (0.056 +/- 0.012 vs. 0.032 +/- 0.005, P = 0.035).
      CONCLUSIONS: These results indicate a decrease in expression of hepatic CYPs and
      their regulator GR in rats exposed to IH. Therefore, this should be noted for
      patients on medication, especially those on drugs metabolized via the hepatic
      system, and close attention should be paid to the liver function of patients with
      OSA-associated IH.

PMID- 29067958
TI  - Magnetic Resonance Gd-RGD Imaging Study of Hepatocellular Carcinoma with High and
      Low Metastatic Potential before and after Human Bone Marrow-derived Mesenchymal
      Stem Cell Intervention.
AB  - BACKGROUND: Biotherapy based on human bone marrow-derived mesenchymal stem cells
      (BMSCs) is currently the focus of research, especially in the field of autologous
      stem cell transplantation. A novel type of metastasis-associated magnetic
      resonance (MR) molecular imaging probe was constructed, and the changes in
      metastasis and proliferation of hepatocellular carcinoma (HCC) before and after
      BMSC intervention were observed through MR imaging (MRI). METHODS: Metastasis
      associated MR molecular imaging probe, integrin alphavbeta3ligand cRGD-PEG-DGL
      DTPA-Gd (Gd-RGD), were constructed. After human BMSC intervention was performed
      for 6 weeks, tumor weight inhibition rates were calculated, and the RGD molecular
      probe was imaged through MRI with molecular imaging agent Gd-DTPA as control. The
      signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the MRI
      experiment were used as semi-quantitative indicators. Polymerase chain reaction
      method was performed to detect proliferation- and metastasis-associated
      indicators, transforming growth factor beta-1 (TGFbeta1), osteopontin (OPN), and
      integrin subunit alphavand beta3. RESULTS: The highest tumor weight inhibition
      rates were observed 3 weeks after the BMSC transplantation. The MR Gd-RGD in the
      HCC tissues after the BMSC intervention showed less enhancement than Gd-DTPA. The
      Gd-DTPA MRI of control group had higher SNR and CNR than Gd-RGD MRI in the
      experimental groups (P < 0.05). For high metastatic potential hepatocellular
      carcinoma (MHCC97-H), significant differences were observed in the SNRs and CNRs
      of Gd-RGD MRI before and after the BMSC intervention (P < 0.05). For low
      metastatic potential hepatocellular carcinoma (MHCC97-L), the CNRs of Gd-RGD MRI
      were statistically different before and after BMSC intervention (P < 0.05). With
      regard to MHCC97-H, OPN, beta3, and TGFbeta1 expression significantly decreased
      after BMSC intervention (P < 0.05). In MHCC97-L and OPN, beta3, TGFbeta1, and
      alphav expression after BMSC intervention decreased, and the difference was
      statistically significant (P < 0.05). CONCLUSIONS: The CNR index of MRI is a good
      indicator for distinguishing high- and low-metastatic potential HCC tissues.
      After BMSC transplantation of MRI through the two kinds of tracer, the SNR and
      CNR indexes can distinguish two kinds of high and low metastatic potential HCC
      tissues, and Gd-RGD imaging is more suitable in distinguishing the metastatic
      potential changes through BMSC intervention.

PMID- 29067959
TI  - Corticosteroid-induced Osteonecrosis of the Femoral Head: Detection, Diagnosis,
      and Treatment in Earlier Stages.
AB  - OBJECTIVE: This review aimed to provide a current recommendation to
      multidisciplinary physicians for early detection, diagnosis, and treatment of
      corticosteroid-induced osteonecrosis of the femoral head (ONFH) based on a
      comprehensive analysis of the clinical literature. DATA SOURCES: For the purpose
      of collecting potentially eligible articles, we searched for articles in the
      PubMed, Cochrane Library, Embase, and CNKI databases up to February 2017, using
      the following key words: "corticosteroid", "osteonecrosis of the femoral head",
      "risk factors", "diagnosis", "prognosis", and "treatment". STUDY SELECTION:
      Articles on relationships between corticosteroid and ONFH were selected for this
      review. Articles on the diagnosis, prognosis, and intervention of earlier-stage
      ONFH were also reviewed. RESULTS: The incidence of corticosteroid-induced ONFH
      was associated with high doses of corticosteroids, and underlying diseases in
      certain predisposed individuals mainly occurred in the first 3 months of
      corticosteroid prescription. The enhanced awareness and minimized exposure to the
      established risk factors and earlier definitive diagnosis are essential for the
      success of joint preservation. When following up patients with ONFH, treatment
      should be started if necessary. Surgical treatment yielded better results than
      conservative therapy in earlier-stage ONFH. The ideal purpose of earlier
      intervention and treatment is permanent preservation of the femoral head without
      physical restrictions in daily living. CONCLUSIONS: Clinicians should enhance
      their precaution awareness of corticosteroid-induced ONFH. For high-risk
      patients, regular follow-up is very important in the 1st year after high-dose
      prescription of corticosteroids. Patients with suspected ONFH should be referred
      to orthopedists for diagnosis and treatment in its earlier stage to preserve the
      joint.

PMID- 29067962
TI  - Concept and Classification of a Derived Injury Resulting from a Primary Injury in
      Orthopedic Trauma.

PMID- 29067961
TI  - Genetic and Clinical Advances of Congenital Muscular Dystrophy.
AB  - OBJECTIVE: The aim was to update the genetic and clinical advances of congenital
      muscular dystrophy (CMD), based on a systematic review of the literature from
      1991 to 2017. DATA SOURCES: Articles in English published in PubMed from 1991 to
      2017 English were searched. The terms used in the literature searches were CMD.
      STUDY SELECTION: The task force initially identified citations for 98 published
      articles. Of the 98 articles, 52 studies were selected after further detailed
      review. Three articles, which were not written in English, were excluded from the
      study. This study referred to all the important and English literature in full.
      RESULTS: CMD is a group of early-onset disorders encompassing great clinical and
      genetic heterogeneity. Patients present with muscle weakness typically from birth
      to early infancy, delay or arrest of gross motor development, and joint and/or
      spinal rigidity. The diagnosis of CMD relies on clinical findings, brain and
      muscle imaging, muscle biopsy histology, muscle and/or skin immunohistochemical
      staining, and molecular genetic testing. CONCLUSIONS: Advances in next-generation
      sequencing and histopathological techniques have enabled the recognition of
      distinct CMD subtypes supported by specific gene identification. Genetic
      counseling and multidisciplinary management of CMD play an important role in help
      patients and their family. Further elucidation of the significant clinical and
      genetic heterogeneity, therapeutic targets, and the clinical care for patients
      remains our challenge for the future.

PMID- 29067963
TI  - New Developments in Treatments of Tibial Plateau Fractures.

PMID- 29067964
TI  - Reconstruction of Tibial Nonossifying Fibroma accompanying with Undetected
      Ewing's Sarcoma by Ilizarov Method.

PMID- 29067965
TI  - Puzzle and Challenge in Differentiating Immunoglobulin G4-related Cholangitis
      from Hilar Cholangiocarcinoma.

PMID- 29067960
TI  - Relationship between Apolipoprotein Superfamily and Parkinson's Disease.
AB  - OBJECTIVE: Parkinson's disease (PD) is featured with motor disorder and nonmotor
      manifestations including psychological symptoms, autonomic nervous system
      dysfunction, and paresthesia, which results in great inconvenience to the
      patients' life. The apolipoprotein (Apo) superfamily, as a group of potentially
      modifiable biomarkers in clinical practice, is of increasing significance in the
      diagnosis, evaluation, and prognosis of PD. The present review summarized the
      current understanding and emerging findings of the relationship between Apo
      superfamily and PD. DATA SOURCES: All literatures were identified by
      systematically searching PubMed, Embase, and Cochrane electronic databases with
      terms "Parkinson disease," "apolipoprotein," and their synonyms until May 2017.
      STUDY SELECTION: We have thoroughly examined titles and abstracts of all the
      literatures that met our search strategy and the full text if the research is
      identified or not so definite. Reference lists of retrieved articles were also
      scrutinized for additional relevant studies. RESULTS: The levels of plasma ApoA1
      are inversely correlated with the risk of PD and the lower levels of ApoA1 trend
      toward association with poorer motor performance. Higher ApoD expression in
      neurons represents more puissant protection against PD, which is critical in
      delaying the neurodegeneration process of PD. It is suggested that APOE alleles
      are related to development and progression of cognitive decline and age of PD
      onset, but conclusions are not completely identical, which may be attributed to
      different ApoE isoforms. APOJ gene expressions are upregulated in PD patients and
      it is possible that high ApoJ level is an indicator of PD dementia and correlates
      with specific phenotypic variations in PD. CONCLUSIONS: The Apo superfamily has
      been proved to be closely involved in the initiation, progression, and prognosis
      of PD. Apos and their genes are of great value in predicting the susceptibility
      of PD and hopeful to become the target of medical intervention to prevent the
      onset of PD or slow down the progress. Therefore, further large-scale studies are
      warranted to elucidate the precise mechanisms of Apos in PD.

PMID- 29067966
TI  - Paralysis Resulting from Calcific Discitis with Acute Herniation.

PMID- 29067967
TI  - Pulmonary Capillary Hemangiomatosis Associated with CREST Syndrome: A Challenge
      of Diagnosis and Treatment.

PMID- 29067968
TI  - World Sickle Cell Day: Lessons for India.

PMID- 29067969
TI  - Therapeutic advances in sickle cell disease in the last decade.

PMID- 29067970
TI  - An insight about genomic susceptibility & multiple sclerosis.

PMID- 29067971
TI  - Designing genetic association studies for complex traits in India.

PMID- 29067972
TI  - Challenges & options in dengue prevention & control: A perspective from the 2015
      outbreak.

PMID- 29067973
TI  - Alzheimer's disease: An alternative approach.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative cortical dementia.
      It starts with memory loss, spatial disorientation in people above the age of 65
      yr with a preference to females. Its incidence is expected to increase threefold
      by 2050. It affects almost one out of ten persons above the age of 65 years.
      Majority of patients are sporadic, but a very small percentage is autosomal
      dominant. The pathomechanisms postulated include amyloid cascade hypothesis
      according to which mutation in amyloid precursor protein causes Abeta
      aggregation. The next hypothesis is signal transducer and activation of
      transcription 3 (STAT3) causing aberration in intracellular signalling pathways.
      Senile plaques and neurofibrillary tangles are other important pathological
      changes reported. It is observed that dementia research has not yielded the
      expected result world over, and therefore, the pitfalls with reference to known
      facts about diagnosis, clinical features, pathogenic mechanisms, assessment of
      progression, biomarkers, treatment and prevention, as well as brief information
      on our experiments with relatively inexpensive methods of differentiating the
      most common types of dementia AD and frontotemporal dementia are discussed.

PMID- 29067974
TI  - Telomere length as a potential biomarker of coronary artery disease.
AB  - Coronary artery disease (CAD) is a multifactorial disease whose prevalence
      remains unabated especially in developing countries. Both lifestyle factors and
      genetic predisposition contribute to this disorder. Though notable achievements
      have been made in the medical, interventional and surgical management of CAD, the
      need for its prevention is more important. Among other modalities, this calls for
      defining evidence-based new biomarkers, which on their own or in combination with
      other known biomarkers may predict the risk of CAD to enable institution of
      appropriate preventive strategies. In the present communication, we have
      discussed the usefulness of shortening of telomeres as a potential biomarker of
      CAD. Clinical research evidence in favour of telomere shortening in CAD is well
      documented in different ethnic populations of the world. Establishing a well
      standardized and accurate method of evaluating telomere length is essential
      before its routine use in preventive cardiology.

PMID- 29067975
TI  - Sudden unexpected death in epilepsy.
AB  - People with epilepsy have increased risk of premature death, and their life
      expectancy may reduce by 2-10 yr. Population- and hospital-based studies have
      shown that the excess mortality in epilepsy is not entirely explained by deaths
      directly attributable to epilepsy such as accidents and drowning during a
      seizure. It is also significantly contributed by deaths from other causes such as
      cardiac deaths, deaths due to malignancies and other causes. It had recently been
      recognized that sudden unexpected deaths in epilepsy (SUDEP) contributed to a
      small yet important proportion of mortality in epilepsy. SUDEPs are deaths
      (witnessed or unwitnessed) unrelated to trauma, drowning or status epilepticus
      and not attributable to any specific medical conditions. Several factors related
      to epilepsy and drug therapy have been found to be associated with higher risk of
      SUDEP.

PMID- 29067976
TI  - Combination of interleukin-10 gene promoter polymorphisms with HLA-DRB1*15 allele
      is associated with multiple sclerosis.
AB  - BACKGROUND & OBJECTIVES: Multiple sclerosis (MS) is common in some ethnic groups.
      Interleukin-10 (IL-10) is a potent anti-inflammatory and immunosuppressive
      cytokine that may be an important regulator in MS disease pathogenesis. IL-10
      promoter includes several single nucleotide polymorphisms and the level of IL-10
      expression is related to these polymorphisms. Furthermore, loci within the
      histocompatibility regions are responsible for susceptibility to MS. The aim of
      this study was to investigate the association of IL-10 gene promoter
      polymorphisms and HLA-DRB1*15 allele frequencies with MS susceptibility in an
      Iranian population. METHODS: In this study 336 MS patients and 454 healthy
      controls were included. Genomic DNA was purified from peripheral blood samples by
      a standard protocol. Genotyping was performed by the sequence-specific primer
      polymerase chain reaction method. RESULTS: IL-10 -1082 G/G and IL-10 -819 C/C
      genotypes were more frequent in MS patients than healthy individuals. DRB1*15
      allele showed a higher frequency among MS patients compared to controls.
      INTERPRETATION & CONCLUSIONS: The IL-10 and HLA-DRB1*15 polymorphisms were
      associated with the susceptibility to MS in Iranian patients. Our results suggest
      that gene-gene interaction of IL-10 polymorphisms and HLA-DRB1*15 alleles may be
      important factors in the development of MS.

PMID- 29067977
TI  - Genetic variations in the Dravidian population of South West coast of India:
      Implications in designing case-control studies.
AB  - BACKGROUND & OBJECTIVES: Indian data have been largely missing from genome-wide
      databases that provide information on genetic variations in different
      populations. This hinders association studies for complex disorders in India.
      This study was aimed to determine whether the complex genetic structure and
      endogamy among Indians could potentially influence the design of case-control
      studies for autoimmune disorders in the south Indian population. METHODS: A total
      of 12 single nucleotide variations (SNVs) related to genes associated with
      autoimmune disorders were genotyped in 370 healthy individuals belonging to six
      different caste groups in southern India. Allele frequencies were estimated;
      genetic divergence and phylogenetic relationship within the various caste groups
      and other HapMap populations were ascertained. RESULTS: Allele frequencies for
      all genotyped SNVs did not vary significantly among the different groups studied.
      Wright's FSTwas 0.001 per cent among study population and 0.38 per cent when
      compared with Gujarati in Houston (GIH) population on HapMap data. The analysis
      of molecular variance results showed a 97 per cent variation attributable to
      differences within the study population and <1 per cent variation due to
      differences between castes. Phylogenetic analysis showed a separation of
      Dravidian population from other HapMap populations and particularly from GIH
      population. INTERPRETATION & CONCLUSIONS: Despite the complex genetic origins of
      the Indian population, our study indicated a low level of genetic differentiation
      among Dravidian language-speaking people of south India. Case-control studies of
      association among Dravidians of south India may not require stratification based
      on language and caste.

PMID- 29067978
TI  - Association of rheumatic fever & rheumatic heart disease with plausible early &
      late-stage disease markers.
AB  - BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD)
      are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a
      major concern in the developing countries due to its poor diagnosis, lack of
      vaccines and social awareness among population. This study was aimed to identify
      the plausible early- and late-stage disease markers associated with RF/RHD.
      METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and
      RHD (n=43) were included in the comparative analysis of different factors
      involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This
      study revealed high titre of serum antistreptolysin O (ASO) antibody in
      pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide
      (PICP) level was elevated in RHD which showed an inverse correlation with serum
      ASO titre. The significant elevation of serum anti-peptide associated with RF
      (PARF) antibody in RF patients was correlated as a probable stage-specific
      determinant. In addition, pro-inflammatory cytokine profile revealed high levels
      of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was
      higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The
      overall assessment of the factors/ disease markers involved in host-pathogen
      interaction in RF/RHD may be suggestive of plausible disease marker in different
      groups of patients. Further studies with larger sample need to be done to better
      understand RF/RHD pathogenesis.

PMID- 29067979
TI  - Peripheral blood mononuclear cells of patients with latent autoimmune diabetes
      secrete higher levels of pro- & anti-inflammatory cytokines compared to those
      with type-1 diabetes mellitus following in vitro stimulation with beta-cell
      autoantigens.
AB  - BACKGROUND & OBJECTIVES: Type-1 diabetes mellitus (T1DM) and latent autoimmune
      diabetes in adults (LADA) share similar pathological features but differ in age
      of onset and progression. There is a scarcity of information on differences in
      CD4+ T-cell responses, particularly, cytokine secretion, between the two forms of
      autoimmune diabetes. Here proliferative potential and concentration of pro- and
      anti-inflammatory cytokines secreted by peripheral blood mononuclear cells
      (PBMCs) of T1DM and LADA patients were compared, after in vitro stimulation with
      beta-cell autoantigens. METHODS: A total of 19 patients with LADA, 37 with T1DM
      and 20 healthy controls were compared on the basis of lymphocyte proliferation
      and secretion of pro- and anti-inflammatory cytokines belonging to different T
      helper types after in vitro stimulation of PBMCs with insulin and glutamic acid
      decarboxylase 65 (GAD65). RESULTS: Following insulin stimulation, LADA group
      secreted higher concentration of interleukin-17 (IL-17) (P=0.02) and had higher
      proportion of interferon gamma (IFN-gamma) secretors (P<0.001) than T1DM group.
      Post-GAD65 stimulation, higher proportion of LADA patients secreted IL-23 than
      T1DM group (P=0.02). Proportion of responders , as well as levels of secreted IL
      10, were significantly higher in LADA than T1DM group, following stimulation with
      both insulin (P=0.01) and GAD65 (P=0.03). A significant positive correlation was
      observed between body mass index and IL-17 levels (r=0.41, P=0.04) and fasting
      plasma C-peptide with IL-10 levels (r=0.37, P=0.04). INTERPRETATION &
      CONCLUSIONS: There are differences in the portfolio of cytokine secretion in
      diabetic subjects with varying rates of beta-cell destruction as LADA subjects
      secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to
      beta-cell autoantigens, thus highlighting another distinguishing feature in the
      pathophysiology of the two forms of autoimmune diabetes.

PMID- 29067980
TI  - Comparative analysis of inflammatory gene expression levels in metabolic syndrome
      & coronary artery disease.
AB  - BACKGROUND & OBJECTIVES: Metabolic syndrome (MetS) increases the likelihood of
      developing coronary artery disease (CAD), and inflammation is involved in the
      pathogenesis of both these conditions. The present work was conducted to examine
      the relative expression of 18 key inflammatory genes associated with MetS and
      incident CAD in a representative group of patients. METHODS: A total of 178 male
      patients, including 57 with CAD and 121 without CAD, were enrolled in the study.
      The participants without CAD were characterized for the presence of MetS using
      modified criteria specific for Asian Indians, which included a lower cut-off for
      waist circumference (>=90 cm for men). The expression of 18 inflammatory genes
      was evaluated in peripheral whole blood by quantitative polymerase chain reaction
      method. RESULTS: Of the 121 participants without CAD, 53 (43.8%) had three or
      more risk factors (MetS group), 50 (41.3%) had one or two risk factors (non-MetS
      group), while 18 (14.8%) did not have any risk factors (control group). High
      nuclear factor-kappa B (NF-kappaB) expression levels and low interleukin-10 (IL
      10) levels were observed in MetS patients. Linear association was seen between NF
      kappaB and vascular endothelial growth factor A (VEGFA) expression and with
      increase in MetS components. Comparison of gene expression pattern between CAD
      and MetS revealed significantly higher expression of leukotriene genes -
      arachidonate 5-lipoxygenase (ALOX5), arachidonate 5-lipoxygenase activating
      protein (ALOX5 AP), leukotriene A4 hydrolase (LTA4H) and leukotriene C4 synthase
      (LTC4S), and lower expression of NF-kappaB, interleukin 1 beta (IL-1beta),
      monocyte chemoattractant protein-1 (MCP-1/CCL2) and signal transducer and
      activator of transcription 3 (STAT3) genes in CAD. There was linear increase in
      expression of LTA4H, LTC4S, IL-8 and VEGFA genes across the four groups, namely
      from controls, non-MetS, MetS and CAD. INTERPRETATION & CONCLUSIONS: A distinct
      gene expression pattern was seen in MetS and CAD implying a well-orchestrated
      inflammatory and immune activity. Specifically, NF-kappaB might be playing an
      active role in MetS, allowing further expansion of the inflammatory process with
      resolution of inflammation in full-blown CAD, wherein other gene players such as
      leukotrienes may dominate.

PMID- 29067981
TI  - Coping in residual schizophrenia: Re-analysis of ways of Coping checklist.
AB  - BACKGROUND & OBJECTIVES: Persons with schizophrenia use various coping strategies
      to adapt to distressing symptoms as well as to deal with daily stressors. Efforts
      have been made to explore alternative frameworks of coping using Ways of Coping
      Checklist (WCC) in persons with schizophrenia. This study aimed to re-analyze
      (factor analysis) the revised-WCC in Indian patients with residual schizophrenia.
      The secondary aim of the study was to evaluate the relationship of new framework
      of coping with psychopathology, disability and quality of life (QOL). METHODS:
      Using a cross-sectional design, 103 patients with residual schizophrenia were
      assessed on WCC. A principal component analysis with varimax rotation was carried
      out to determine the factor structure of WCC. RESULTS: Factor analysis yielded
      six factors which explained 51.6 per cent of the total variance and had
      acceptable-to-good internal consistency. Based on the type of items loaded, the
      six factors were named as follows: active and growth-oriented coping, accepting
      and fantasizing, reflective and confrontative coping, detachment, seeking social
      support and negative emotional coping. Patients most often used coping strategy
      of seeking social support, followed by 'accepting and fantasizing' and 'active
      and growth-oriented coping'. Correlation analysis showed that those who more
      often used 'active and growth-oriented coping' had less negative symptoms, lower
      level of disability and higher spiritual and overall QOL. INTERPRETATION &
      CONCLUSIONS: The factor structure of revised-WCC was different among patients
      with schizophrenia when compared with individuals without mental illness, living
      in the community. It was evident that use of certain adaptive coping strategies
      was associated with better QOL and lower level of psychopathology. Our findings
      provided a framework of coping in patients with residual schizophrenia and
      suggested that promotion of certain coping strategies might be useful in
      improving the QOL and reduction of psychopathology in patients with
      schizophrenia.

PMID- 29067982
TI  - Clinical significance of magnetic resonance imaging findings in chronic low
      backache.
AB  - BACKGROUND & OBJECTIVES: Magnetic resonance imaging (MRI) is frequently done for
      the evaluation of chronic low backache (CLBA), however, its significance in
      Indian patients has not been evaluated. We report here the MRI findings in
      patients with CLBA and their sensitivity and specificity with clinical evidence
      of radiculopathy and localized CLBA as well as correlate these with pain severity
      and disability. METHODS: Seventy two patients with CLBA aged 20-70 yr without
      trauma, infection, tumour, metastasis and vascular malformation were included in
      the study. Their demographic characteristics, lifestyle, education and employment
      were noted. Lumbosacral MRI was carried out and 19 MRI parameters at six levels
      (D12-L1-L5-S1) were noted. The severity of pain was assessed by Numeric Rating
      Scale (NRS, 0-10) and disability by Oswestry Disability Index (ODI). RESULTS: MRI
      was abnormal in all patients, the most common being disc desiccation (90.3%)
      followed by facet joint arthropathy (FJA; 75%) and nerve root compression (NRC;
      72.2%). Endplate changes and high-intensity zone were noted in 58 and 50 per cent
      of patients, respectively. One-third patients with FJA, however, were below 30 yr
      of age. NRC on MRI had 61.3 per cent sensitivity and 10 per cent specificity with
      clinical radiculopathy. FJA had 60.7 per cent sensitivity and 15.9 per cent
      specificity with localized CLBA. None of the MRI parameters and MRI sum score
      correlated with NRS and ODI. On multivariate analysis, NRS was independent
      predictor of ODI (odds ratio 0.58, 95% confidence interval 0.35-0.98, P=0.04).
      INTERPRETATION & CONCLUSIONS: In patients with CLBA, NRC on MRI showed poor
      specificity with corresponding clinical radiculopathy and FJA with localized
      backache. None of the MRI abnormality correlated with the severity of pain or
      disability.

PMID- 29067983
TI  - Occurrence, patterns & predictors of hypogonadism in patients with HIV infection
      in India.
AB  - BACKGROUND & OBJECTIVES: Data on hypogonadism among human immunodeficiency virus
      (HIV)-infected Indians are not available. This study was aimed to evaluate the
      occurrence, pattern and predictors of hypogonadism in HIV-infected Indians.
      METHODS: Consecutive stable HIV-infected patients, 18-70 yr age, without any
      severe comorbid state, having at least one year follow up data at the
      antiretroviral therapy clinic, underwent clinical assessment and hormone assays.
      RESULTS: From initially screened 527 patients, 359 patients (225 males; 134
      females), having disease duration of 61.44+/-39.42 months, 88.58 per cent on
      highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis
      history and 89.69 per cent with vitamin D insufficiency were analyzed.
      Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary,
      hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed
      in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism
      were significantly older (P=0.009), and had higher opportunistic infections
      (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were
      observed in 40.3 per cent females, who were significantly older (P<0.001), had
      lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3,
      16.2 and 13 per cent women with menstrual abnormalities were in peri-/post
      menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively.
      Age, CD4 count at diagnosis and 25(OH)D were best predictors of male
      hypogonadism. Age and CD4 count increment in first 6-12 months following HAART
      were the best predictors of POI. INTERPRETATION & CONCLUSIONS: Hypogonadism was
      observed to be a significant problem in HIV-infected men and women in India,
      affecting 39 and 29 per cent patients, respectively. HypoH was the most common
      form in males whereas ovarian failure being the most common cause in females.

PMID- 29067984
TI  - Association between intimate partner violence & HIV/AIDS: Exploring the pathways
      in Indian context.
AB  - BACKGROUND & OBJECTIVES: Violence against women cutting across diverse socio
      economic classes is an under-recognized human rights violation in the world. This
      analysis was undertaken to examine the prevalence along with predictors of
      intimate partner violence (IPV) and its association with HIV/AIDS and sexually
      transmitted infections (STIs) in Indian ever-married women. METHODS: The data
      obtained from 2005 to 2006 third round of National Family Health Survey-3 (NFHS
      3) were used in this study. Analyses were conducted on ever-married women by
      linking individual women data including violence information and HIV test
      results. RESULTS: The analyses indicated all forms of violence to be prevalent in
      India. The prevalence of lifetime IPV reported was 35.3 per cent. Multivariate
      analysis using logistic regression identified younger age of women, higher number
      of children, low level of education of women as well as her partner, working
      status of women, higher spousal age, rural residence, alcohol consumption by
      husband, childhood witness of violence among parents, nuclear household and lower
      standard of living to be positively associated with the experience of IPV by the
      women (P<0.05). HIV-positive status of women, as well as women from high HIV
      prevalent State, were at increased odds of IPV (P<0.05). INTERPRETATION &
      CONCLUSIONS: Significantly higher reporting of HIV/STIs by women experiencing IPV
      hints at new pathways that link violence and HIV. Further, our analysis showed a
      high prevalence of IPV in India.

PMID- 29067985
TI  - Point prevalence & risk factor assessment for hospital-acquired infections in a
      tertiary care hospital in Pune, India.
AB  - BACKGROUND & OBJECTIVES: Hospital-acquired infections (HAIs) are a major
      challenge to patient safety and have serious public health implications by
      changing the quality of life of patients and sometimes causing disability or even
      death. The true burden of HAI remains unknown, particularly in developing
      countries. The objective of this study was to estimate point prevalence of HAI
      and study the associated risk factors in a tertiary care hospital in Pune, India.
      METHODS: A series of four cross-sectional point prevalence surveys were carried
      out between March and August 2014. Data of each patient admitted were collected
      using a structured data entry form. Centers for Disease Control and Prevention
      guidelines were used to identify and diagnose patients with HAI. RESULTS: Overall
      prevalence of HAI was 3.76 per cent. Surgical Intensive Care Unit (ICU) (25%),
      medical ICU (20%), burns ward (20%) and paediatric ward (12.17%) were identified
      to have significant association with HAI. Prolonged hospital stay [odds ratio
      (OR=2.81), mechanical ventilation (OR=18.57), use of urinary catheter (OR=7.89)
      and exposure to central air-conditioning (OR=8.59) had higher odds of acquiring
      HAI (P<0.05). INTERPRETATION & CONCLUSIONS: HAI prevalence showed a progressive
      reduction over successive rounds of survey. Conscious effort needs to be taken by
      all concerned to reduce the duration of hospital stay. Use of medical devices
      should be minimized and used judiciously. Healthcare infection control should be
      a priority of every healthcare provider. Such surveys should be done in different
      healthcare settings to plan a response to reducing HAI.

PMID- 29067986
TI  - Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from
      patients with CNS tuberculosis infection.
AB  - BACKGROUND & OBJECTIVES: Central nervous system (CNS) infection caused by
      Mycobacterium tuberculosis (MTB) is the most severe form of extrapulmonary
      tuberculosis (EPTB) due to a high level of mortality and morbidity. Limited
      studies are available on CNS-TB animal model development. The present study
      describes the development of a murine model of CNS-TB using a clinical strain
      (C3) isolated from the cerebrospinal fluid (CSF) of CNS-TB patients. METHODS:
      Groups of mice were infected by the intravenous route with MTB C3 strain isolated
      from the CSF of CNS-TB patients. Brain and lung tissue were evaluated for
      bacterial burden, histopathology and surrogate markers of TB infection at 30 and
      50 days post-infection. RESULTS: Mice infected intravenously with MTB C3 strains
      showed progressive development of CNS disease with high bacillary burden in lungs
      at the initial stage (30 days), which eventually disseminated to the brain at a
      later stage (50 days). Similarly, high mortality (60%) was associated in mice
      infected with C3 strain compared to control. INTERPRETATION & CONCLUSIONS: The
      study showed development of a novel murine model of CNS-TB using the C3 strain of
      MTB that replicated events of extrapulmonary dissemination. The developed model
      would be helpful in understanding the pathogenesis of CNS-TB infection for the
      development of improved therapeutic interventions in future.

PMID- 29067988
TI  - Report of diphtheria cases & surveillance among contacts in Dibrugarh, Assam,
      India.

PMID- 29067987
TI  - Toxigenic Clostridium difficile isolates from clinically significant diarrhoea in
      patients from a tertiary care centre.
AB  - BACKGROUND & OBJECTIVES: Clostridium difficile is the primary cause of hospital
      acquired colitis in patients receiving antibiotics. The pathogenicity of the
      organism is mainly due to the production of toxins. This study was conducted to
      investigate the presence of toxigenic C. difficile in the faecal samples of
      hospitalized patients suspected to have C. difficile infection (CDI) and
      corroborating the findings with their clinical and demographic data. METHODS:
      Diarrhoeic samples obtained from 1110 hospitalized patients were cultured for C.
      difficile and the isolates confirmed by phenotypic and molecular methods.
      Toxigenicity of the isolates was determined using enzyme-linked immunosorbent
      assay for toxins A and B. Details of patients included in the study were noted
      and analyzed. RESULTS: Of the 1110 patients (mean age 39+/-19.6 yr), 63.9 per
      cent were males and 36.1 per cent were females. The major antibiotics received by
      the patients were nitazoxanide (23.9%), penicillins/penicillin combinations
      (19.0%), quinolones including fluoroquinolones (13.1%), carbapenems (11.5%),
      glycopeptides (11.0%) and cephalosporins (8.4%). The clinical symptoms
      predominantly present were watery diarrhoea (56.4%), fever (40.0%) and abdominal
      pain (35.3%). The underlying diseases were gastrointestinal disorders (52.6%),
      followed by cancers (13.2%), surgical conditions (8.3%), and hepatic disorders
      (8.0%). Of the 174 C. difficile isolates, 54.6 per cent were toxigenic. Toxigenic
      C. difficile was present in all patients with surgical conditions, 65.2 per cent
      with cancers and 57.1 per cent with gastrointestinal disorders. INTERPRETATION &
      CONCLUSIONS: C. difficile was found to be an important cause of gastrointestinal
      infections in hospitalized patients with underlying diseases and on antibiotics.
      Clinical conditions of the patients correlating with toxigenic culture can be an
      important tool for establishing CDI diagnosis.

PMID- 29067990
TI  - Erratum.
AB  - [This corrects the article DOI: 10.4103/ijmr.IJMR_409_17.].

PMID- 29067989
TI  - Elephantiasis nostras verrucosa.

PMID- 29067991
TI  - Treatment of secondary hyperparathyroidism with paricalcitol with or without
      cinacalcet in hemodialysis patients.
AB  - INTRODUCTION    Secondary hyperparathyroidism (SHPT) is a common hormonal
      disorder associated with chronic kidney disease (CKD). The treatment of SHPT
      should lead to a reduction in parathormone concentrations by calcimimetics or
      active vitamin D administration and stabilization of calciumand phosphate
      metabolism. In the event of failure of conservative treatment, complete or
      partial parathyroid resection should be considered. OBJECTIVES    The aim of the
      study was to assess the beneficial effects of a combination treatment with
      paricalcitol and cinacalcet in comparison with paricalcitol alone. PATIENTS AND
      METHODS    A total of 64 hemodialyzed patients (mean [SD] age, 58 [16] years)
      with inadequate control of serum parathyroid hormone levels were treated with
      intravenous paricalcitol, while 16 patients simultaneously received oral
      cinacalcet. Laboratory tests (intact parathormone [iPTH], calcium, phosphorus)
      were performed on a monthly basis. In the study, iPTH, calium, phosphorus, and
      alkaline phosphatase levels were assessed at baseline and after 24 weeks of
      treatment with paricalcitol alone or in combination with cinacalcet. RESULTS   
      In both groups, a significant decrease in the iPTH level was observed. Although
      paricalcitol affects calcium levels, no hypercalcemia was observed. The
      combination treatment did not result in a significant lowering of iPTH levels in
      comparison with paricalcitol alone. CONCLUSIONS    Treatment of SHPT with
      intravenous paricalcitol in patients on hemodialysis is effective and has a good
      safety profile. The combination of paricalcitol and cinacalcet does not improve
      the outcomes. Moreover, the combined treatment does not affect calcium and
      phosphorus concentrations. The cost-effectiveness of therapy should also be
      considered.

PMID- 29067992
TI  - Medical cannabis for the treatment of chronic pain and other disorders:
      misconceptions and facts.
AB  - Recently, many countries have enacted new cannabis policies, including
      decriminalization of cannabis possession as well as legalization of medical and
      recreational cannabis. In this context, patients and their physicians have had an
      increasing number of conversations about the risks and benefits of cannabis.
      While cannabis and cannabinoids continue to be evaluated as pharmacotherapy for
      medical conditions, the best evidence currently exists for the following medical
      conditions: chronic pain, neuropathic pain, and spasticity resulting from
      multiple sclerosis. We also reviewed the current state of evidence for cannabis
      and cannabinoids for several other medical conditions, while addressing the
      potential acute and chronic effects of cannabis use, which are issues that
      physicians must consider before making an official recommendation on the use of
      medical cannabis to a patient. As the number of patient requests for medical
      cannabis has been increasing, physicians must become knowledgeable on the science
      of medical cannabis and open to a discussion about why the patient feels that
      medical cannabis may be helpful.

PMID- 29067993
TI  - Transcription: Intragenic enhancers dampen gene expression.

PMID- 29067994
TI  - Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty
      acids.
AB  - The mammalian gastrointestinal tract harbors a microbial community with metabolic
      activity critical for host health, including metabolites that can modulate
      effector functions of immune cells. Mice treated with vancomycin have an altered
      microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2)
      responses, and are more susceptible to allergic lung inflammation. Here we show
      that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates
      this enhanced asthma susceptibility by modulating the activity of T cells and
      dendritic cells (DCs). Dysbiotic mice treated with SCFAs have fewer interleukin-4
      (IL4)-producing CD4+ T cells and decreased levels of circulating immunoglobulin E
      (IgE). In addition, DCs exposed to SCFAs activate T cells less robustly, are less
      motile in response to CCL19 in vitro, and exhibit a dampened ability to transport
      inhaled allergens to lung draining nodes. Our data thus demonstrate that gut
      dysbiosis can exacerbate allergic lung inflammation through both T cell- and DC
      dependent mechanisms that are inhibited by SCFAs.

PMID- 29067995
TI  - Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime-boost
      immunization.
AB  - Tissue-resident memory (TRM) CD8 T cells survey a range of non-lymphoid mucosal
      tissues where they rapidly mediate clearance of viral infections at the entry
      portals. Vaccines that establish CD8 TRM cells in the cervicovaginal mucosa hold
      promise for effective immunity against sexually transmitted HIV. We demonstrate
      that HIV-specific CD8 TRM cells can be established in the murine vaginal mucosa
      using a combined intranasal and intravaginal mucosal immunization with
      recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence
      microscopy, we found that this mucosally administered prime-boost immunization
      also resulted in the durable seeding of CD8 T cells in the frontline vaginal
      epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen
      recognition within the vaginal mucosa, these HIV-specific CD8 TRM cells rapidly
      initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 TRM
      cells resulted in the upregulation of endothelial vessel addressin expression and
      substantial recruitment of both adaptive and innate immune cells in the vaginal
      mucosa. These findings suggest that the epithelial localization of HIV-specific
      CD8 TRM cell populations and their capacity to rapidly activate both arms of the
      immune system could significantly augment frontline defenses against vaginal HIV
      infection.

PMID- 29067997
TI  - IL-33 promotes gastrointestinal allergy in a TSLP-independent manner.
AB  - This corrects the article DOI: 10.1038/mi.2017.61.

PMID- 29067996
TI  - The survival of fetal and bone marrow monocyte-derived alveolar macrophages is
      promoted by CD44 and its interaction with hyaluronan.
AB  - Alveolar macrophages maintain lung homeostasis by performing important roles in
      immunosurveillance and lung surfactant catabolism. They express high levels of
      CD44 and are one of the few macrophage populations that constitutively bind
      hyaluronan, a ligand for CD44 and component of pericellular and extracellular
      matrices. Using adoptive transfer experiments and a mouse model of inflammation,
      we found that alveolar macrophages are initially depleted after an inflammatory
      insult then rapidly self-renew and return to original numbers after the
      resolution phase. Monocytes recruited to an inflamed lung differentiate and
      contribute to the alveolar macrophage pool, but this occurs over a much slower
      time frame than alveolar macrophage self-renewal. CD44 expression on both fetal
      and bone marrow-derived alveolar macrophages promoted their survival and provided
      a competitive advantage over CD44-deficient alveolar macrophages at homeostasis
      and after inflammation. CD44-mediated hyaluronan binding was induced by the
      alveolar environment, and this interaction promoted alveolar macrophage survival
      both ex vivo and in vivo. Without CD44, alveolar macrophages lacked a hyaluronan
      coat, were more susceptible to death, and were present at lower numbers in the
      alveolar space. This demonstrates a new role for CD44 and hyaluronan in promoting
      alveolar macrophage survival.

PMID- 29067998
TI  - Epithelial-derived TGF-beta1 acts as a pro-viral factor in the lung during
      influenza A infection.
AB  - Mucosal surfaces are under constant bombardment from potentially antigenic
      particles and so must maintain a balance between homeostasis and inappropriate
      immune activation and consequent pathology. Epithelial cells have a vital role
      orchestrating pulmonary homeostasis and defense against pathogens. TGF-beta
      regulates an array of immune responses-both inflammatory and regulatory-however,
      its function is highly location- and context-dependent. We demonstrate that
      epithelial-derived TGF-beta acts as a pro-viral factor suppressing early immune
      responses during influenza A infection. Mice specifically lacking bronchial
      epithelial TGF-beta1 (epTGFbetaKO) displayed marked protection from influenza
      induced weight loss, airway inflammation, and pathology. However, protection from
      influenza-induced pathology was not associated with a heightened lymphocytic
      immune response. In contrast, the kinetics of interferon beta (IFNbeta) release
      into the airways was significantly enhanced in epTGFbetaKO mice compared with
      control mice, with elevated IFNbeta on day 1 in epTGFbetaKO compared with control
      mice. This induced a heighted antiviral state resulting in impaired viral
      replication in epTGFbetaKO mice. Thus, epithelial-derived TGF-beta acts to
      suppress early IFNbeta responses leading to increased viral burden and pathology.
      This study demonstrates the importance of the local epithelial microenvironmental
      niche in shaping initial immune responses to viral infection and controlling host
      disease.

PMID- 29067999
TI  - MyD88-dependent dendritic and epithelial cell crosstalk orchestrates immune
      responses to allergens.
AB  - Sensitization to inhaled allergens is dependent on activation of conventional
      dendritic cells (cDCs) and on the adaptor molecule, MyD88. However, many cell
      types in the lung express Myd88, and it is unclear how signaling in these
      different cell types reprograms cDCs and leads to allergic inflammation of the
      airway. By combining ATAC-seq with RNA profiling, we found that MyD88 signaling
      in cDCs maintained open chromatin at select loci even at steady state, allowing
      genes to be rapidly induced during allergic sensitization. A distinct set of
      genes related to metabolism was indirectly controlled in cDCs through MyD88
      signaling in airway epithelial cells (ECs). In mouse models of asthma, Myd88
      expression in ECs was critical for eosinophilic inflammation, whereas Myd88
      expression in cDCs was required for Th17 cell differentiation and consequent
      airway neutrophilia. Thus, both cell-intrinsic and cell-extrinsic MyD88 signaling
      controls gene expression in cDCs and orchestrates immune responses to inhaled
      allergens.

PMID- 29068000
TI  - beta-Glucans in food modify colonic microflora by inducing antimicrobial protein,
      calprotectin, in a Dectin-1-induced-IL-17F-dependent manner.
AB  - Dectin-1 (gene symbol: Clec7a) is a receptor for beta-glucans that play an
      important role for the host defense against fungi. Recently, we showed that
      Clec7a-/- mice are resistant against dextran sodium sulfate (DSS)-induced colitis
      because of regulatory T-cell population expansion in the colon. The regulatory T
      cell expansion is caused by expansion of commensal Lactobacillus murinus whose
      growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this
      report, we showed that S100A8 was mainly produced by mouse colonic epithelial
      cells. S100A8 was not induced directly by Dectin-1 but by Dectin-1-induced
      cytokines, especially interleukin-17F (IL-17F), that were produced by several
      types of innate immune cells including CD11c+/CD11b+ myeloid cells in colonic
      lamina propria. S100A8/A9 heterodimer preferentially suppressed the growth of L.
      murinus that was increased in both Clec7a-/- and Il17f-/- mice. Furthermore,
      similar expansion of L. murinus and DSS-colitis resistance were observed in mice
      fed with beta-glucan-free food. These observations suggest that food-derived beta
      glucans control the specific commensal microbiota via the Dectin-1-IL-17F
      calprotectin axis to maintain the intestinal homeostasis.

PMID- 29068003
TI  - Understanding and targeting resistance mechanisms in NSCLC.
AB  - The expanding spectrum of both established and candidate oncogenic driver
      mutations identified in non-small-cell lung cancer (NSCLC), coupled with the
      increasing number of clinically available signal transduction pathway inhibitors
      targeting these driver mutations, offers a tremendous opportunity to enhance
      patient outcomes. Despite these molecular advances, advanced-stage NSCLC remains
      largely incurable due to therapeutic resistance. In this Review, we discuss
      alterations in the targeted oncogene ('on-target' resistance) and in other
      downstream and parallel pathways ('off-target' resistance) leading to resistance
      to targeted therapies in NSCLC, and we provide an overview of the current
      understanding of the bidirectional interactions with the tumour microenvironment
      that promote therapeutic resistance. We highlight common mechanistic themes
      underpinning resistance to targeted therapies that are shared by NSCLC subtypes,
      including those with oncogenic alterations in epidermal growth factor receptor
      (EGFR), anaplastic lymphoma kinase (ALK), ROS1 proto-oncogene receptor tyrosine
      kinase (ROS1), serine/threonine-protein kinase b-raf (BRAF) and other less
      established oncoproteins. Finally, we discuss how understanding these themes can
      inform therapeutic strategies, including combination therapy approaches, and
      overcome the challenge of tumour heterogeneity.

PMID- 29068002
TI  - Engineered D2R Variants Reveal the Balanced and Biased Contributions of G-Protein
      and beta-Arrestin to Dopamine-Dependent Functions.
AB  - The dopamine D2 receptor (D2R), like many G-protein-coupled receptors, signals
      through G-protein- and beta-arrestin-dependent pathways. Preferential activation
      of one of these pathways is termed functional selectivity or biased signaling and
      is a promising therapeutic strategy. Though biased signaling through D2Rs has
      been demonstrated, acquiring the mechanistic details of biased D2R/G-protein and
      D2R/beta-arrestin signaling in vivo has been challenging because of the lack of
      techniques that specifically target these interactions in discrete cell
      populations. To address this question, we employed a cell type-specific viral
      expression approach to restore D2R variants that preferentially engage either G
      protein or beta-arrestin signaling in 'indirect pathway' medium spiny neurons
      (iMSNs), because of their central role in dopamine circuitry. We found that the
      effect of haloperidol antagonism on D2R metabolic signaling events is largely
      mediated by acute blockade of D2R/G-protein signaling. We show that a D2R-driven
      behavior, nestlet shredding, is similarly driven by D2R/G-protein signaling. On
      the other hand, D2R-driven locomotion and rearing require coordinated D2R/G
      protein and D2R/beta-arrestin signaling. The acute locomotor response to
      amphetamine and cocaine similarly depend on both G-protein and beta-arrestin D2R
      signaling. Surprisingly, another psychotropic drug, phencyclidine, displayed a
      selective D2R/beta-arrestin potentiation of locomotion. These findings highlight
      how D2R mostly relies upon balanced G-protein and beta-arrestin signaling in
      iMSNs. However, the response to haloperidol and phencyclidine indicates that
      normal D2R signaling homeostasis can be dramatically altered, indicating that
      targeting a specific D2R signal transduction pathway could allow for more precise
      modulation of dopamine circuit function.

PMID- 29068004
TI  - Targeted therapies: Understanding tumour drug addiction.

PMID- 29068005
TI  - Corrigendum: Microscopic origins of the large piezoelectricity of leadfree
      (Ba,Ca)(Zr,Ti)O3.
AB  - This corrects the article DOI: 10.1038/ncomms15944.

PMID- 29068007
TI  - Facile synthesis of CoNix nanoparticles embedded in nitrogen-carbon frameworks
      for highly efficient electrocatalytic oxygen evolution.
AB  - We report a pyrolysis reduction method to prepare highly uniform dispersed CoNix
      nanoparticles embedded in nitrogen-carbon frameworks. With an appropriate value
      of Ni/Co, the obtained CoNi0.37-CN catalyst exhibited excellent properties and
      stability in electrocatalytic oxygen evolution, which are superior to those of
      the commercial IrO2.

PMID- 29068006
TI  - A stretchable polysiloxane elastomer with self-healing capacity at room
      temperature and solvatochromic properties.
AB  - A stretchable silicon elastomer comprising cobalt ions in pyridine pendant
      polydimethylsiloxane (PDMS) was prepared. Different from previously reported
      cobalt-coordinated elastomers, these elastomers are self-healable at room
      temperature with a high healing efficiency of over 90%. Besides, they exhibit
      tailored solvatochromic properties over a wide range without sacrificing its self
      healing ability at room-temperature.

PMID- 29068008
TI  - The influence of covalent immobilization conditions on antibody accessibility on
      nanoparticles.
AB  - The accessibility of particle-coupled antibodies is important for many analytical
      applications, but comprehensive data on parameters controlling the accessibility
      are scarce. Here we report on the site-specific accessibility of monoclonal
      antibodies, immobilized on magnetic nanoparticles (500 nm) by the widely used
      covalent EDC coupling method, with the variation of four key coupling parameters
      (surface activation and immobilization pH, crosslinker and antibody concentration
      ratios). By developing quantitative radio-labelled assays, the number of
      immobilized antibodies, the Fab domain accessibility (in a sandwich immunoassay),
      and the Fc domain accessibility (in a Protein G assay) were determined. For sub
      monolayer surface coverage, the observed numbers of accessible Fab and Fc domains
      are equal and scale linearly with the antibody density. For above monolayer
      coverage, the fractions of accessible Fab and Fc domains decrease, in an unequal
      manner. The results show that the antibody accessibility is primarily determined
      by the antibody surface density, rather than by chemical reactivity or the charge
      state, and that crowded conditions affect Fab and Fc accessibility in an unequal
      manner.

PMID- 29068009
TI  - Catalytic reduction of SO2 by CO over Au4Pt2(CO)n and Au6Pt(CO)n clusters: a
      first-principles study.
AB  - The catalytic properties of the magic gold-platinum bimetallic clusters (Au4Pt2
      and Au6Pt) for the reduction of SO2 by CO, without or with preadsorbing CO
      molecules, are firstly investigated using density functional theory calculations.
      We find that the catalytic activities improve effectively with the preadsorption
      of CO onto the catalysts and that the catalytic activities of Au6Pt(CO)n are
      better than those of Au4Pt2(CO)n as more CO molecules are adsorbed onto the
      catalysts. During the reaction process, the Au4Pt2(CO)n clusters always keep two
      dimensional morphologies except for when n = 5 and the Au6Pt(CO)n clusters have
      three-dimensional geometries except for when n = 0. The most stable adsorption
      site for SO2 molecules on the catalysts is the site of preadsorbing the next CO
      molecule on the corresponding catalysts. The largest activation energy (E) is
      related to the metal 5d (M-5d) band center and the charge transfer (Ct) as well
      as the bond length (Rb) between COS and the catalyst contribute to the desorption
      energy (Ed) of COS corporately. We propose that Au6Pt(CO)6 is a cost-effective
      gold-platinum bimetallic catalyst for the reduction of SO2 by CO.

PMID- 29068010
TI  - Versatile palladium-catalyzed double carbonylation of aryl bromides.
AB  - A versatile palladium-catalyzed double carbonylation of aryl bromides has been
      developed. Using Pd(OAc)2/BuPAd2 as the catalyst system and DBU as the base,
      under relatively low CO pressure, various alpha-ketoamides were produced in good
      yields. In order to get insight into the reaction pathway, real time NMR studies
      were performed as well and a correlated reaction mechanism is been given.

PMID- 29068012
TI  - A platinum porphyrin modified TiO2 electrode for photoelectrochemical hydrogen
      production from neutral water driven by the conduction band edge potential of
      TiO2.
AB  - The onset potential for H2 production from neutral water (pH 7) catalyzed by a
      platinum(ii) porphyrin (PtP-py) modified TiO2 electrode positions very close to
      the standard water reduction potential (less than 50 mV). H2 production is driven
      by the conduction band edge potential of TiO2 at the PtP-py-modified TiO2
      cathode.

PMID- 29068013
TI  - Cooperative influence of pseudohalides and ligand backbone of Schiff-bases on
      nuclearity and stereochemistry of cobalt(iii) complexes: experimental and
      theoretical investigation.
AB  - Four cobalt(iii) complexes, [Co(HL1)(NCS)2(EtOH)] (1), [Co2(L1)2(N3)2] (2) and
      [Co(HL2)(NCS)2(EtOH)] (3), [Co(HL2)(N3)2] (4) were synthesized from two Schiff
      base ligands namely, (E)-2-((2-(2-hydroxyethylamino)ethylimino)methyl)phenol
      (H2L1) and (E)-2-((3-(2-hydroxyethylamino)propylimino)methyl)phenol (H2L2),
      respectively. All the four complexes have been thoroughly characterised by using
      various physicochemical studies such as UV-Vis, FT-IR, ESI-MS, EPR and single
      crystal X-ray diffraction. Depending on flexibility of the ligand backbone subtle
      structural differences are observed in the synthesized complexes. In complex 1
      the two thiocyanate ligands are trans to each other whereas in complex 3 they are
      cis to each other with addition of one additional methylene (-CH2-) group to the
      ligand system. Complex 2 is dinuclear while complex 4 is mononuclear in the
      presence of the azide co-anionic ligand. Theoretical studies are carried out in
      order to rationalize the structural differences observed in the complexes.
      Catecholase like activity of all the four complexes were performed in N,N
      dimethylformamide (DMF) using 3,5-di-tert-butylcatechol (3,5-DTBC) as a model
      substrate. Complex 2 was found to exhibit the highest activity. Mechanistic
      investigation of the catecholase like activity revealed the formation of the
      imine radical during catalytic reactions of complexes 2 and 4 which are further
      corroborated by the EPR study.

PMID- 29068016
TI  - A supramolecular assembly of metal-free organic dye with zinc porphyrin
      chromophore for dye-sensitized solar cells.
AB  - Two porphyrin chromophores, P1 and P2, were prepared and used as antenna units to
      coordinate with a metal-free organic dye, JH1, containing pyridine groups. This
      supramolecular self-assembly strategy can not only effectively improve the light
      harvesting ability of the devices but also effectively reduces electron
      recombination by preventing I3- of the electrolyte from penetrating into the TiO2
      surface. The DSSC based on JH1 showed a PCE of 2.46%, with a Voc of 615 mV, Jsc
      of 6.54 mA cm-2, and FF of 61.18%. After supramolecular self-assembly, the Jsc
      and Voc of the device were greatly improved. Specifically for the device based on
      JH1 + P2, the PCE reached 4.39%, which is about 78% greater than the PCE of the
      device based on JH1; this is mainly due to the Jsc increase of 2.85 mA cm-2 and
      the Voc increase of 93 mV. Compared to co-sensitization, supramolecular self
      assembly does not require tedious optimization steps; thus, this may be a
      promising and convenient way to improve the overall performance of DSSCs.

PMID- 29068014
TI  - Multifunctional UCNPs@MnSiO3@g-C3N4 nanoplatform: improved ROS generation and
      reduced glutathione levels for highly efficient photodynamic therapy.
AB  - Photodynamic therapy (PDT) is a novel technique that has been extensively
      employed in cancer treatment; it utilizes reactive oxygen species to kill
      malignant cells. However, poor performance of the photosensitizer itself, limited
      penetration depth and the overexpression of glutathione (GSH) in cancer cells are
      the major obstacles facing the actual clinical application of PDT. Inspired by
      the challenges mentioned above, here we propose multifunctional nanoparticles
      utilizing mesoporous manganese silicate (MnSiO3)-coated upconversion
      nanoparticles (UCNPs) as nanocarriers for loading highly fluorescent graphitic
      phase carbon nitride quantum dots (g-C3N4 QDs) to simultaneously act as a
      photosensitive drug and imaging agent. Surface modification of the nanoparticles
      with polyethylene glycol (PEG) endows the samples (denoted as UMCNs-PEG) with
      excellent biocompatibility and long-term in vivo circulation. Taking advantage of
      the inherent performance of the as-synthesized nanoparticles, multimodality
      imaging, including upconversion luminescence (UCL), computed tomography (CT) and
      magnetic resonance imaging (MRI), has been achieved; this is conducive to
      providing effective treatment information by real-time monitoring. In vivo
      photodynamic therapy to achieve effective tumor inhibition was then realized
      without inducing significant toxicity to treated mice. As a result, this work
      provides a novel paradigm with highly integrated functionalities which not only
      exhibits excellent prospects for imaging-guided photodynamic anticancer therapy
      but also encourages further exploration of new types of multifunctional
      nanoparticles for biomedical applications.

PMID- 29068017
TI  - Benzannulated Re(i)-NHC complexes: synthesis, photophysical properties and
      antimicrobial activity.
AB  - A series of novel Re(i)(CO)3-NHC complexes bearing unsubstituted benzimidazol-2
      ylidene ligands as well as a variety of bisimine ligands has been prepared and
      comprehensively characterised. The complexes were found to exhibit potent
      antimicrobial activity on Gram-positive bacterial strains in the low micromolar
      concentration range, rendering these compounds interesting lead structures for
      the development of novel metal-based antibiotic agents. Further, the complexes
      exhibit pronounced luminescence with large Stokes shifts in acetonitrile and
      water at ambient temperature. The photophysical properties including luminescence
      lifetimes and quantum yields are consistent with emission from 3MLCT (d(Re) ->
      pi*(bisimine)) states.

PMID- 29068018
TI  - Mono- and binuclear chiral N,N,O-scorpionate zinc alkyls as efficient initiators
      for the ROP of rac-lactide.
AB  - The preparation of new chiral bis(pyrazol-1-yl)methane-based N,N,O-donor
      scorpionate ligands in the form of the alcohol compounds bpzampeH (1) {2,2
      bis(3,5-dimethylpyrazol-1-yl)-1-[4-(dimethylamino)phenyl]ethanol}, bpzaepeH (2)
      {2,2-bis(3,5-dimethylpyrazol-1-yl)-1-[4-(diethylamino)phenyl]ethanol}, and
      bpzimeH (3) {2,2-bis(3,5-dimethylpyrazol-1-yl)-1-[1-methyl-1H-imidazol-2
      yl]ethanol} has been carried out by the 1,2-addition reactions of a series of
      aldehydes. These new chiral heteroscorpionate ligands reacted with [ZnR2] (R =
      Me, Et, CH2SiMe3) in a 1 : 1 molar ratio in toluene to give the mononuclear
      monoalkyl zinc complexes [Zn(R)(kappa3-NNO)] (4-12). When these reactions were
      carried out in a 1 : 2 molar ratio the binuclear trisalkyls [Zn(R)(kappa2-NNMU
      O)Zn(R)2] (13-18) were obtained. The structures of these complexes were
      elucidated by 1H and 13C{1H} NMR spectroscopy and the X-ray crystal structures of
      4 and 5 were also established. Interestingly, alkyl-containing zinc complexes 4
      13, 15 and 17 act as efficient single-component initiators for the ring-opening
      polymerization of rac-lactide at 20  degrees C to afford PLA materials with low
      molecular weights in a few hours. The dinuclear trisalkyls showed higher activity
      in comparison with the mononuclear zinc counterparts, suggesting a cooperative
      effect of the two remote metals. The narrow dispersity ranges (Mw/Mn = 1.05) of
      the isolated polymers in conjunction with the linear nature of the number average
      molecular weight versus conversion plot provided evidence for living behavior.
      Inspection of the kinetic parameters showed that the propagations have the usual
      pseudo-first-order dependence on rac-lactide and catalyst concentration. End
      group analysis and MALDI-TOF mass spectrometry confirmed that the initiation
      occurs through nucleophilic attack of the alkyl on the lactide monomer.
      Microstructural analysis of poly(rac-lactide)s revealed that the most sterically
      hindered ligand on the alkoxide fragment exerts a moderate influence on the
      degree of stereoselectivity, with heteroenriched-PLAs (Ps = 0.68) produced at
      room temperature.

PMID- 29068019
TI  - A microfluidic device for partial immobilization, chemical exposure and
      behavioural screening of zebrafish larvae.
AB  - The zebrafish larva is an important vertebrate model for sensory-motor
      integration studies, genetic screening, and drug discovery because of its
      excellent characteristics such as optical transparency, genetic manipulability,
      and genetic similarity to humans. Operations such as precise manipulation of
      zebrafish larvae, controlled exposure to chemicals, and behavioural monitoring
      are of utmost importance to the abovementioned studies. In this work, a novel
      microfluidic device is presented to easily stabilize an individual larva's head
      using a microfluidic trap while leaving the majority of the body and the tail
      unhindered to move freely in a downstream chamber. The device is equipped with a
      microvalve to prevent the larva's escape from the trap and a microchannel beside
      the larva's head to expose it to chemicals at desired concentrations and times,
      while investigating multiple behaviours such as the tail, eye, and mouth movement
      frequencies. An in situ air bubble removal module was also incorporated to
      increase the yield of experiments. The functionality of our device in comparison
      to a conventional droplet-based technique was tested using l-arginine exposure
      and viability assays. We found that the larvae in the device and the droplet
      exhibit similar tail and eye response trends to nM-mM concentrations of l
      arginine, and that the survival of the larvae is not affected by the device.
      However, the tail responses in the device were numerically higher than the
      droplet-tested larvae at nM-mM l-arginine concentrations. In the future, our
      device has the potential to be used for conducting simultaneous whole-brain
      functional imaging, upon optimized immobilization of the brain, and behavioural
      analysis to uncover differences between diseased and healthy states in zebrafish.

PMID- 29068020
TI  - A microporous MOF with a polar pore surface exhibiting excellent selective
      adsorption of CO2 from CO2-N2 and CO2-CH4 gas mixtures with high CO2 loading.
AB  - A microporous MOF {[Zn(SDB)(L)0.5].S}n (IITKGP-5) with a polar pore surface has
      been constructed by the combination of a V-shaped -SO2 functionalized organic
      linker (H2SDB = 4,4'-sulfonyldibenzoic acid) with an N-rich spacer (L = 2,5-bis(3
      pyridyl)-3,4-diaza-2,4-hexadiene), forming a network with sql(2,6L1) topology.
      IITKGP-5 is characterized by TGA, PXRD and single crystal X-ray diffraction. The
      framework exhibits lozenge-shaped channels of an approximate size of 4.2 * 5.6 A2
      along the crystallographic b axis with a potential solvent accessible volume of
      26%. The activated IITKGP-5a revealed a CO2 uptake capacity of 56.4 and 49 cm3 g
      1 at 273 K/1 atm and 295 K/1 atm, respectively. On the contrary, it takes up a
      much smaller amount of CH4 (17 cm3 g-1 at 273 K and 13.6 cm3 g-1 at 295 K) and N2
      (5.5 cm3 g-1 at 273 K; 4 cm3 g-1 at 295 K) under 1 atm pressure exhibiting its
      potential for a highly selective adsorption of CO2 from flue gas as well as a
      landfill gas mixture. Based on the ideal adsorbed solution theory (IAST), a
      CO2/N2 selectivity of 435.5 and a CO2/CH4 selectivity of 151.6 have been realized
      at 273 K/100 kPa. The values at 295 K are 147.8 for CO2/N2 and 23.8 for CO2/CH4
      gas mixtures under 100 kPa. In addition, this MOF nearly approaches the target
      values proposed for PSA and TSA processes for practical utility exhibiting its
      prospect for flue gas separation with a CO2 loading capacity of 2.04 mmol g-1.

PMID- 29068021
TI  - Two metal-organic frameworks based on a flexible benzimidazole carboxylic acid
      ligand: selective gas sorption and luminescence.
AB  - Two new three-dimensional (3D) porous metal-organic frameworks (MOFs),
      {[Cd2(L)(NMP)(H2O)2].2H2O}n (1) and {[Zn(L)0.5(H2O)].NMP.H2O}n (2), have been
      solvothermally synthesized by using Zn(ii) and Cd(ii) ions with H4L (H4L = 1,4
      di(5,6-bicarboxylbenzimidazol-lylmethyl)benzene) in different ratios of H2O and
      NMP (NMP = 1-methyl-2-pyrrolidinone) solvents, all of which have been
      characterized by elemental analysis, FT-IR spectroscopy, powder X-ray diffraction
      (PXRD), and thermogravimetric analysis (TGA). As revealed by structural analysis,
      the H4L ligand took different coordination fashions in 1 and 2, and as a result,
      two MOFs with a novel (3,4,7)-connected trinodal net and (3,6)-connected binodal
      net were obtained, respectively. The structure comparison reveals that the
      coordination modes of ligands and the types of metal ions play decisive roles in
      regulating the final networks of MOFs. The desolvated frameworks 1 and 2 possess
      polar channels decorated with uncoordinated carboxylate groups, leading to an
      excellent ability to attract CO2 as well as significant adsorption selectivity
      for CO2 over CH4 at 273 and 298 K. Solid state 1 and 2 show blue
      photoluminescence.

PMID- 29068022
TI  - Revisit of the Saito-Dresselhaus-Dresselhaus C2 ingestion model: on the mechanism
      of atomic-carbon-participated fullerene growth.
AB  - We introduce a mechanistic study based on a controversial fullerene bottom-up
      growth model proposed by R. Saito, G. Dresselhaus, and M. S. Dresselhaus. The so
      called SDD C2 addition model has been dismissed as chemically inadmissible but
      here we prove that it is feasible via successive atomic-carbon-participated
      addition and migration reactions. Kinetic calculations on the formation of
      isolated pentagon rule (IPR)-obeying C70 and Y3N@C80 are carried out by employing
      the SDD model for the first time. A stepwise mechanism is proposed with a
      considerably low barrier of ca. 2 eV which is about 3 eV lower than a
      conventional isomerization-containing fullerene growth pathway.

PMID- 29068023
TI  - Microfluidic channel-coupled 3D quartz nanohole arrays for high capture and
      release efficiency of BT20 cancer cells.
AB  - Nanostructured materials, such as silicon nanowires, quartz nanostructures, and
      polymer-modified nanostructures, are a promising new class of materials for the
      capture and enumeration of very rare tumor cells, including circulating tumor
      cells (CTCs), to examine their biological characteristics in whole blood of
      cancer patients. These cells can then be used for transplantation, anti-tumor
      cell therapy, and cell-secreted protein studies. It is believed that 3
      dimensional (3D) nanostructured substrates efficiently enhance cell capture
      yields due to the increased local contacts between the 3D nanostructures and
      extracellular extensions of the tumor cells. Recent studies have been performed
      with enhanced cell capture yields thanks to various nanostructured platforms;
      however, there remains an urgent need both to capture and release viable rare
      tumor cells for further molecular (i.e., protein) analysis and to develop patient
      specific drugs. Here, we first demonstrate that our 3D quartz nanohole array
      (QNHA) tumor cell capture and release system allows us not only to selectively
      capture rare tumor cells, but also to release the cells with high capture and
      release rates. This system was developed using streptavidin (STR)-functionalized
      QNHA (STR-QNHA) with a microfluidic channel. Our system has ideal cell-separation
      yields of as high as 85-91% and high release rates of >90% for the BT20 cell
      line. We suggest that the use of a microfluidic channel technique coupled with a
      STR-QNHA cell capture and release chip (STR-QNHA cell chip) would be a powerful
      and simple process to evaluate the capture, enumeration, and release of CTCs from
      patient whole blood for studying further cell therapy and tumor-cell-secreted
      molecules.

PMID- 29068024
TI  - Achiral polyamine-induced chiral zinc gallophosphates with fused double helix
      like strands exhibiting blue to green photoluminescence.
AB  - This study found non-chiral polyamines to be effective in inducing chiral
      frameworks. Four zinc gallophosphates with a chiral UCSB-7 topology were
      generated from the use of four different linear-chain polyamines as templates. In
      the structure, helical inorganic strands and templates appeared to fuse into a
      double helix-like arrangement. Notably, they are the first chiral frameworks to
      display optical analogues and intriguing photoluminescence properties.

PMID- 29068025
TI  - A novel oxalate-based three-dimensional coordination polymer showing magnetic
      ordering and high proton conductivity.
AB  - A novel three-dimensional (3D) coordination polymer with the formula
      (C3N2H5)4[MnCr2(ox)6].5H2O (2), where ox = oxalate and C3N2H5 = imidazolium
      cation, is reported. Single crystal X-ray diffraction reveals that this porous
      coordination polymer adopts a chiral three-dimensional quartz-like architecture,
      with the guest imidazolium cations and water molecules being hosted in its pores.
      This novel multifunctional material exhibits both a ferromagnetic ordering at TC
      = 3.0 K, related to the host MnCr2 network, and high proton conductivity [1.86 *
      10-3 S cm-1 at 295 K and 88% relative humidity (RH)] due to the presence of the
      acidic imidazolium cations and free water molecules. The similarity of the
      structure of compound 2 to that of the previously reported analogous compound
      (NH4)4[MnCr2(ox)6].4H2O, (1), also allows us to analyse, to a certain extent, the
      effect of the acidity of the proton donating guest molecules on proton conduction
      properties. 2 hosts, in one-dimensional (1D) channels, imidazolium cations, which
      are more acidic than the ammonium ones in 1 and, as a consequence, 2 shows higher
      proton conduction than 1, highlighting the effect of the pKa of the proton
      donating guest molecules on proton conductivity.

PMID- 29068026
TI  - MBE growth of Al/InAs and Nb/InAs superconducting hybrid nanowire structures.
AB  - We report the in situ growth of crystalline aluminum (Al) and niobium (Nb) shells
      on indium arsenide (InAs) nanowires. The nanowires are grown on Si(111)
      substrates by molecular beam epitaxy (MBE) without foreign catalysts in the vapor
      solid (VS) mode. The metal shells are deposited by electron-beam evaporation in a
      metal MBE. High quality superconductor/semiconductor (SC/SM) hybrid structures
      such as Al/InAs and Nb/InAs are of interest for ongoing research in the fields of
      gateable Josephson junctions and quantum information related research. Systematic
      investigations of the deposition parameters suitable for metal shell growth are
      conducted. In the case of Al, the substrate temperature, the growth rate and the
      shell thickness are considered. The substrate temperature as well as the angle of
      the impinging deposition flux are explored for Nb shells. The core-shell hybrid
      structures are characterized by electron microscopy and X-ray spectroscopy. Our
      results show that the substrate temperature is a crucial parameter in enabling
      the deposition of smooth Al layers. Contrarily, Nb films are less dependent on
      substrate temperature but are strongly affected by the deposition angle. At a
      temperature of 200  degrees C Nb reacts with InAs, dissolving the nanowire
      crystal. Our investigations result in smooth metal shells exhibiting an impurity
      and defect free, crystalline SC/InAs interface. Additionally, we find that the SC
      crystal structure is not affected by stacking faults present in the InAs
      nanowires.

PMID- 29068027
TI  - Preventive effects of taurine against d-galactose-induced cognitive dysfunction
      and brain damage.
AB  - Oxidative stress arising from life processes or environmental influences and its
      resultant cellular dysfunctions are major causes of neurodegenerative disorders.
      The objectives of this study were to investigate whether taurine (Tau) can
      prevent d-galactose-induced cognitive dysfunction and brain oxidative damage.
      Mice given with Tau supplementation (100 and 400 mg per kg BW per day) spent
      shorter (p < 0.05) time in searching target in d-galactose (100 mg per kg BW per
      day) treated mice in a water maze reference memory experiment. Moreover, Tau
      supplementation extended (p < 0.05) the searching period around the target
      quadrant in the probe test of the water maze, and neuronal degeneration and
      nucleus shrinkage in the hippocampus dentate gyrus area of d-galactose treated
      mice were observed to be attenuated. Tau also downregulated (p < 0.05) expression
      of the glial fibrillary acidic protein (Gfap) and of the cluster of
      differentiation marker Cd11b; meanwhile, it strengthened (p < 0.05) antioxidant
      capacity and lowered (p < 0.05) the accumulation of advanced glycation end
      products (AGEs) in the brain. Therefore, Tau could be effective to ameliorate
      oxidative damage and inflammation in the brain, and apoptosis of brain cells,
      which further lessen the cognitive dysfunction.

PMID- 29068030
TI  - Catalyst free boron carbon bond cleavage and facile formation of five-membered
      PNBCC heterocycles.
AB  - The [3 + 2] cycloaddition reaction of phosphanyl aminoborane [N(2,6
      iPr2C6H3)(PPh2)(BCy2)] (1) with activated alkynes led to boron and phosphorus
      containing five-membered heterocycles [(2,6-iPr2C6H3)NPPh2(CO2R)C
      C(Cy)(CO2R)(BCy)] [R = Me (2), Et (3) and H (4)] with facile cleavage of the B-C
      bond and concomitant formation of a P-C bond with an ylidic character. DFT
      calculations indicate that 1 can be considered as a non-conjugated 1,3-dipole
      having two reaction centers viz., a nucleophilic P-center and an electrophilic B
      center. The reaction of 1 with the alkynes proceeds through a stepwise dipolar
      addition mechanism, followed by the migration of the cyclohexyl group from the B
      atom to the adjacent C-atom.

PMID- 29068033
TI  - Superconductivity and magnetotransport of single-crystalline NbSe2 nanoplates
      grown by chemical vapour deposition.
AB  - NbSe2 is a typical transition metal dichalcogenide with a rich variety of
      electronic ground states existing in its nanostructures, including two
      dimensional superconductivity and charge density wave. However, the direct growth
      of high-quality single-crystalline NbSe2 nanostructures is still challenging,
      which limits their applications in electronic devices. Here, we report the growth
      of high-quality NbSe2 nanoplates by a single-step chemical vapour deposition.
      Their temperature and magnetic-field dependent superconducting behaviors were
      investigated by four-terminal devices fabricated on individual nanostructures.
      The NbSe2 nanoplates show two-dimensional characteristics of superconducting
      transitions and strong anisotropy with magnetic field orientation, providing
      potential platforms for the exploration of new physics in nanoelectronic devices.

PMID- 29068034
TI  - Characterization of fecal fat composition and gut derived fecal microbiota in
      high-fat diet fed rats following intervention with chito-oligosaccharide and
      resistant starch complexes.
AB  - The current study analyzed the different effects of intervention in high-fat diet
      fed rats using chito-oligosaccharides (CO group), resistant starch (RS group) and
      their complexes (CO-RS group), respectively. Properties such as fecal fat
      composition, gut derived fecal microbiota and fecal metabolites were
      investigated. The results show that supplementation with CO-RS in the high-fat
      diet led to the highest level of fecal fat excretion, followed by the CO and RS
      groups, and its fatty acid composition was characterized by a lower ?UFA and
      higher ?SFA levels. Furthermore, CO-RS consumption significantly enhanced the
      excretion of bile acids in the feces, which might be associated with a higher
      conversion of cholesterol into bile acids and the enhanced binding capacity with
      the bile acids. The fecal microbiota profile using amplified V4 rDNA suggested
      that rats in the CO-RS group developed an increased richness and diversity in the
      gut bacterial community compared to the high-fat diet group. More importantly,
      the CO-RS intake significantly increased the abundance of both Lactobacillus and
      Bifidobacterium, indicating their potential use as prebiotics. Furthermore, the
      highest abundance of Allobaculum and Blautia genus in the feces of the CO-RS
      group was also found in this study, which is highly related to the highest
      production of short-chain fatty acids (SCFAs) in the colon among all the animals
      groups. A histological analysis of colon tissue revealed that the CO-RS
      supplemented diet was associated with a greater degree of thickness of the mucosa
      layer compared to the rats in the untreated high-fat diet group. The resulting
      shift in the gut microbiome, increased metabolite (SCFAs) production and
      increased thickness of the mucosal layer may provide profound influences of CO-RS
      consumption on gut protection.

PMID- 29068036
TI  - Pain and fear avoidance partially mediate change in muscle strength during
      resistance exercise in women with fibromyalgia.
AB  - OBJECTIVES: Resistance exercise results in health benefits in fibromyalgia. The
      aim of this study was to determine the factors that mediate change in muscle
      strength in women with fibromyalgia as a result of resistance exercise. METHODS:
      Sixty-seven women with fibromyalgia (age range 25-64 years) were included. Tests
      of muscle strength and questionnaires related to pain, fear avoidance and
      physical activity were carried out. Multivariable stepwise regression was used to
      analyse explanatory factors for change and predictors for final values of knee
      extension force, elbow-flexion force and hand-grip force. RESULTS: Change in knee
      extension force was explained by fear avoidance beliefs about physical activity
      at baseline, together with change in pain intensity, knee-extension force at
      baseline, age and body mass index (BMI) (R2=0.40, p = 0.013). Change in elbow
      flexion force was explained by pain intensity at baseline, together with baseline
      fear avoidance beliefs about physical activity, BMI and elbow-flexion force at
      baseline (R2 = 0.32, p = 0.043). Change in hand-grip force was explained by hand
      grip force at baseline, change in pain intensity and baseline fear avoidance (R2
      = 0.37, p = 0.009). Final muscle strength was predicted by the same variables as
      change, except pain. CONCLUSION: Pain and fear avoidance are important factors to
      consider in rehabilitation using resistance exercise for women with fibromyalgia.

PMID- 29068037
TI  - Berg Balance Scale score at admission can predict walking suitable for community
      ambulation at discharge from inpatient stroke rehabilitation.
AB  - OBJECTIVE: This retrospective cohort study identified inpatient rehabilitation
      admission variables that predict walking ability at discharge and established
      Berg Balance Scale cut-off scores to predict the extent of improvement in
      walking. METHODS: Participants (n=123) were assessed for various cognitive and
      physical outcomes at admission to inpatient stroke rehabilitation. Multivariate
      logistic regression identified admission predictors of regaining community
      ambulation (gait speed >=0.8 m/s) or unassisted ambulation (no physical
      assistance) after 4 weeks. Receiver operating characteristic curve analysis
      identified cut-off admission Berg Balance Scale scores. RESULTS: Mini-Mental
      State Examination (odds ratio (OR) 1.60, 95% confidence interval (95% CI) 1.19
      2.14) was a significant predictor when coupled with admission walking speed for
      regaining community ambulation speed; stroke type (haemorrhagic/ischaemic) was a
      significant predictor (OR=0.19, 95% CI 0.05-0.77) when coupled with Berg Balance
      Scale (OR 1.14, 95% CI 1.09-1.20). Only Berg Balance Scale was a significant
      predictor of regaining unassisted ambulation (OR 1.11, 95% CI 1.05-1.17). A cut
      off Berg Balance Scale score of 29 on admission predicts that an individual will
      go on to achieve community walking speed (n=123, area under the curve (AUC)=0.88,
      95% CI 0.81-0.95); a cut-off score of 12 predicts a non-ambulator to regain
      unassisted ambulation (n=84, AUC 0.73, 95% CI 0.62-0.84). CONCLUSION: The Berg
      Balance Scale can be used at rehabilitation admission to predict the degree of
      improvement in walking for patients with stroke.

PMID- 29068038
TI  - Upper-limb sensory impairments after stroke: Self-reported experiences of daily
      life and rehabilitation.
AB  - OBJECTIVE: To describe stroke survivors' experiences of sensory impairment in the
      upper limb, the influence of such impairment on daily life, coping strategies
      used, and sensory training for the affected hand. DESIGN: A qualitative study
      with a content analysis approach. SUBJECTS: Fifteen post-stroke patients
      interviewed individually. RESULTS: Five categories emerged from the data:
      "Changed and varied perception of the sensation"; "Affected movement control";
      "Problems using the hand in daily life"; "Various strategies to cope with upper
      limb disability"; and "Lack of sensory training". Numbness and tingling, changes
      in temperature sensitivity, and increased sensitivity to touch and pain were
      reported. Many subjects had difficulty adjusting their grip force and performing
      movements with precision. It was problematic and mentally fatiguing managing
      personal care and carrying out household and leisure activities. Practical
      adaptations, compensation with vision, increased concentration, and use of the
      less affected hand were strategies used to overcome difficulties. Despite their
      problems very few subjects had received any specific sensory training for the
      hand. CONCLUSION: Stroke survivors perceive that sensory impairment of the upper
      limb has a highly negative impact on daily life, but specific rehabilitation for
      the upper limb is lacking. These findings imply that the clinical management of
      upper limb sensory impairment after stroke requires more attention.

PMID- 29068039
TI  - Respiratory, cardiovascular and metabolic responses during different modes of
      overground bionic ambulation in persons with motor-incomplete spinal cord injury:
      A case series.
AB  - OBJECTIVE: To investigate the effects of overground bionic ambulation with
      variable assistance on cardiorespiratory and metabolic responses in persons with
      motor-incomplete spinal cord injury. DESIGN: Case series. SUBJECTS: Four
      participants with chronic, motor-incomplete spinal cord injury. METHODS: Subjects
      completed a maximal graded exercise test on an arm-ergometer and 3 6-min bouts of
      overground bionic ambulation using different modes of assistance, i.e. Maximal,
      Adaptive, Fixed. Cardiorespiratory (oxygen consumption) and metabolic (caloric
      expenditure and substrate utilization) measures were taken using a mobile
      metabolic cart at each overground bionic ambulation assistance. RESULTS:
      Cardiorespiratory responses ranged from low (24% VO2peak) for the least impaired
      and fittest individual to supramaximal (124% VO2peak) for the participant with
      the largest impairments and the lowest level of fitness. Different overground
      bionic ambulation assistive modes elicited small (3-8% VO2peak) differences in
      cardiorespiratory responses for 3 participants. One participant had a large (28%
      VO2peak) difference in cardiorespiratory responses to different modes of
      overground bionic ambulation. Metabolic responses mostly tracked closely with
      cardiorespiratory responses. Total energy expenditure ranged from 1.39 to 7.17
      kcal/min. Fat oxidation ranged from 0.00 to 0.17 g/min across participants and
      different overground bionic ambulation modes. CONCLUSION: Overground bionic
      ambulation with variable assistance can substantially increase cardiorespiratory
      and metabolic responses; however, these responses vary widely across participants
      and overground bionic ambulation modes.

PMID- 29068040
TI  - Electrophysiological effects of desflurane in children with Wolff-Parkinson-White
      syndrome: a randomized crossover study.
AB  - BACKGROUND: We hypothesized that, compared with propofol, desflurane prolongs the
      antegrade accessory pathway effective refractory period (APERP) in children
      undergoing radiofrequency catheter ablation for Wolff-Parkinson-White (WPW)
      syndrome. METHODS: In this randomized crossover study, children aged 4.1-16.1
      years undergoing radiofrequency catheter ablation for WPW syndrome were randomly
      divided into four groups according to the concentration of desflurane and
      anesthetics used in the first and the second electrophysiological studies (EPS).
      After induction of general anesthesia with propofol and tracheal intubation, they
      received one of the following regimens: 0.5 minimum alveolar concentration (MAC)
      desflurane (first EPS) and propofol (second EPS) (Des0.5-Prop group, n = 8);
      propofol (first EPS) and 0.5 MAC desflurane (second EPS) (Prop-Des0.5 group, n =
      9); 1 MAC desflurane (first EPS) and propofol (second EPS) (Des1.0-Prop group, n
      = 10); propofol (first EPS) and 1 MAC desflurane (second EPS) (Prop-Des1.0 group,
      n = 9). Radiofrequency catheter ablation was performed upon completion of EPS.
      Sample size was determined to detect a difference in the APERP. RESULTS:
      Desflurane at 1.0 MAC significantly prolonged the APERP compared with propofol,
      but did not affect the sinoatrial conduction time, atrio-His interval or
      atrioventricular node effective refractory period. Supraventricular tachycardia
      was induced in all children receiving propofol, but not induced in 1 and 4
      children receiving 0.5 MAC and 1.0 MAC desflurane, respectively. CONCLUSION:
      Desflurane enhances the refractoriness and may block the electrical conduction of
      the atrioventricular accessory pathway, and is therefore not suitable for use in
      children undergoing radiofrequency catheter ablation for WPW syndrome.

PMID- 29068041
TI  - Point-of-care versus central laboratory testing of INR in acute stroke.
AB  - OBJECTIVES: Effective anticoagulant therapy is a contraindication to
      thrombolysis, which is an effective treatment of ischemic stroke if given within
      4.5 hours of symptom onset. INR above 1.7 is generally considered a
      contraindication for thrombolysis. Rapid measurement of INR in warfarin-treated
      patients is therefore of major importance in order to be able to decide on
      thrombolysis or not. We asked whether INR measured on a point-of-care instrument
      would be as good as a central laboratory instrument. MATERIAL AND METHODS: A
      total of 529 consecutive patients who arrived at the emergency department at a
      large urban teaching hospital with stroke symptoms were enrolled in the study.
      INR was measured with a CoaguChek and a Sysmex instrument. Basic clinical
      information such as age, sex, and diagnosis (if available) was recorded. INR from
      the instruments was compared using linear regression and Bland-Altman plot.
      RESULTS: Of 529 patients, 459 had INR results from both instruments. Among these,
      3 patients were excluded as outliers. The rest (n = 456) showed good correlation
      between the methods (R2  = 0.97). In the current setting, CoaguChek was in median
      63 minutes faster than Sysmex. CONCLUSION: Our results indicate that point-of
      care testing is a safe mean to rapidly acquire a patient's INR value in acute
      clinical situations.

PMID- 29068042
TI  - High volatile anaesthetic conservation with a digital in-line vaporizer and a
      reflector.
AB  - BACKGROUND: A volatile anaesthetic (VA) reflector can reduce VA consumption (VAC)
      at the cost of fine control of its delivery and CO2 accumulation. A digital in
      line vaporizer and a second CO2 absorber circumvent both of these limitations. We
      hypothesized that the combination of a VA reflector with an in-line vaporizer
      would yield substantial VA conservation, independent of fresh gas flow (FGF) in a
      circle circuit, and provide fine control of inspired VA concentrations. METHOD:
      Prospective observational study on six Yorkshire pigs. A secondary anaesthetic
      circuit consisting of a Y-piece with 2 one-way valves, an in-line vaporizer and a
      CO2 absorber in the inspiratory limb was connected to the patient's side of the
      VA reflector. The other side was connected to the Y-piece of a circle anaesthetic
      circuit. In six pigs, an inspired concentration of sevoflurane of 2.5% was
      maintained by the in-line vaporizer. We measured VAC at FGF of 1, 4 and 10 l/min.
      RESULTS: With the secondary circuit, VAC was 55% less than with the circle system
      alone at FGF 1 l/min, and independent of FGF over the range of 1-10 l/min.
      Insertion of a CO2 absorber in the secondary circuit reduced Pet CO2 by 1.3-2.0
      kpa (10-15 mmHg). CONCLUSION: A secondary circuit with reflector and in-line
      vaporizer provides highly efficient anaesthetic delivery, independent of FGF. A
      second CO2 absorber was necessary to scavenge the CO2 reflected by the
      anaesthetic reflector. This secondary circuit may turn any open circuit
      ventilator into an anaesthetic delivery unit.

PMID- 29068043
TI  - Life-history strategies of the rock hind grouper Epinephelus adscensionis at
      Ascension Island.
AB  - Epinephelus adscensionis sampled from Ascension Island, South Atlantic Ocean,
      exhibits distinct life-history traits, including larger maximum size and size at
      sexual maturity than previous studies have demonstrated for this species in other
      locations. Otolith analysis yielded a maximum estimated age of 25 years, with
      calculated von Bertalanffy growth parameters of: Linfinity  = 55.14, K = 0.19, t0
      = -0.88. Monthly gonad staging and analysis of gonad-somatic index (IG ) provide
      evidence for spawning from July to November with an IG peak in August (austral
      winter), during which time somatic growth is also suppressed. Observed patterns
      of sexual development were supportive of protogyny, although further work is
      needed to confirm this. Mean size at sexual maturity for females was 28.9 cm
      total length (LT ; 95% C.I. 27.1-30.7 cm) and no females were found >12 years and
      48.0 cm LT , whereas all confirmed males sampled were mature, >35.1 cm LT with an
      age range from 3 to 18 years. The modelled size at which 50% of individuals were
      male was 41.8 cm (95% C.I. 40.4-43.2 cm). As far as is known, this study
      represents the first comprehensive investigation into the growth and reproduction
      of E. adscensionis at its type locality of Ascension Island and suggests that the
      population may be affected less by fisheries than elsewhere in its range.
      Nevertheless, improved regulation of the recreational fishery and sustained
      monitoring of abundance, length frequencies and life-history parameters are
      needed to inform long-term management measures, which could include the creation
      of marine reserves, size or temporal catch limits and stricter export controls.

PMID- 29068044
TI  - Contrast-enhanced sonothrombolysis in acute ischemic stroke patients without
      intracranial large-vessel occlusion.
AB  - BACKGROUND: Contrast-enhanced sonothrombolysis (CEST) leads to a more rapid
      recanalization in acute ischemic stroke caused by intracranial large-vessel
      occlusion (LVO). Animal studies have shown that CEST also may be safe and
      efficient in treating the ischemic microcirculation in the absence of LVO. The
      exact mechanism behind this treatment effect is not known. We aimed to assess
      safety and efficacy of CEST in acute ischemic stroke patients included in the
      Norwegian Sonothrombolysis in Acute Stroke Study (NOR-SASS) without LVO on
      admission CT angiography (CTA). METHODS: NOR-SASS was a randomized controlled
      trial of CEST in ischemic stroke patients treated with intravenous thrombolysis
      within 4.5 hours after stroke onset. Patients were randomized to either CEST or
      sham CEST. In this study, patients were excluded if they had partial or total
      occlusion on admission CTA, ultrasound-resistant bone window, had received CEST
      with incorrect insonation as compared to stroke location on Magnetic resonance
      imaging (MRI), or were stroke mimics. RESULTS: Of the 183 patients included in
      NOR-SASS, a total of 83 (45.4%) patients matched the inclusion criteria, of which
      40 received CEST and 43 sham CEST. There were no patients with symptomatic
      intracranial hemorrhage (sICH) in the CEST group. Rates of asymptomatic ICH,
      microbleeds, and mortality were not increased in the CEST group. Neurological
      improvement at 24 hours and functional outcome at 90 days were similar in both
      groups. CONCLUSION: CEST is safe in ischemic stroke patients without intracranial
      LVO. There were no differences in clinical outcomes between the treatment groups.

PMID- 29068045
TI  - Larval body condition regulates predator-induced life-history variation in a
      dragonfly.
AB  - Organisms with complex life cycles commonly exhibit adaptive plasticity in the
      timing of transitions between life stages. While the threat of predation is
      predicted to induce earlier transitions, empirical support has been equivocal.
      When predation risk affects both the propensity to transition to the next life
      stage and the ability to reach the energetic thresholds necessary to complete the
      transition, only those individuals in the best physiological condition may be
      able to accelerate development and emerge earlier. To test this hypothesis, we
      followed uniquely marked dragonfly larvae (Pachydiplax longipennis) through
      emergence in pools where we factorially manipulated the presence of a large
      heterospecific predator (Anax junius) and cannibalism risk via conspecific size
      variation. Consistent with our hypothesis, high-condition larvae were more likely
      to emerge in the presence of the heterospecific predator than in its absence, and
      low-condition larvae were more likely to emerge in its absence than in its
      presence. Moreover, high-condition larvae emerged earlier when cannibalism risk
      was high than when it was low. Predation risk therefore has condition-dependent
      effects on emergence. As predation risk frequently affects resource accumulation,
      similar mechanisms across taxa could commonly underlie the incongruence between
      empirical results and theoretical expectations for predator-induced life-history
      variation.

PMID- 29068047
TI  - A multivariate assessment of the Dali hominin cranium from China: Morphological
      affinities and implications for Pleistocene evolution in East Asia.
AB  - OBJECTIVES: A nearly complete hominin fossil cranium from Dali in Shaanxi
      Province, China was excavated in 1978. We update and expand on previous research
      by providing a multivariate analysis of the specimen relative to a large sample
      of Middle and Late Pleistocene hominins. MATERIALS AND METHODS: We apply
      principal components analysis, discriminant function analysis, and a method of
      assessing group membership based on a soft independent model of class analogy
      (SIMCA) to the study of Dali's cranial morphology. We evaluate Dali's affinities
      within the context of Middle and Late Pleistocene Homo patterns of craniofacial
      morphology. RESULTS: When just the facial skeleton is considered, Dali aligns
      with Middle Paleolithic H. sapiens and is clearly more derived than African or
      Eurasian Middle Pleistocene Homo. When just the neurocranium is considered, Dali
      is most similar to African and Eastern Eurasian but not Western European Middle
      Pleistocene Homo. When both sets of variables are considered together, Dali
      exhibits a unique morphology that is most closely aligned with the earliest H.
      sapiens from North Africa and the Levant. DISCUSSION: These results add
      perspective to our previous view of as Dali a "transitional" form between Chinese
      H. erectus and H. sapiens. Athough no taxonomic allocation is appropriate at this
      time for Dali, it appears to represent a population that played a more central
      role in the origin of Chinese H. sapiens. Dali's affinities can be understood in
      the context of Wu's Continuity with Hybridization scenario and a braided-stream
      network model of gene flow. Specifically, we propose that Pleistocene populations
      in China were shaped by periods of isolated evolutionary change within local
      lineages at certain times, and gene flow between local lineages or between
      Eastern and Western Eurasia, and Africa at other times, resulting in
      contributions being made in different capacities to different regions at
      different times.

PMID- 29068048
TI  - Possibilities for developing texture-modified beef steaks suitable for older
      consumers using fruit-derived proteolytic enzymes.
AB  - : Meat intakes in the older population are commonly reduced because the
      relatively tough texture of meat can impair mastication. Fruit-derived
      proteolytic enzymes have been reported to have beneficial effects on tenderness,
      by causing significant degradation of myofibrillar proteins and collagen. Three
      treatments including: papain, bromelain, and a 50:50 mixture of papain/bromelain,
      alongside one control were applied to beef M. semitendinosus steaks. Effects on
      Warner-Bratzler shear force, texture parameters, color, and cook loss were
      determined. Both enzymatic treatments that included papain significantly reduced
      Warner-Bratzler shear force values (p < .05) and increased cook loss. Beef steaks
      tenderized with papain and papain/bromelain offer potential for inclusion in
      older consumers' diets, but improvement in tenderization may be associated with a
      reduction in processing yield. PRACTICAL APPLICATIONS: Meat processors have a
      role to play in enhancing the availability of appropriate foodstuffs for older
      people, through developing targeted products that will meet the specialized
      nutritional and chemosensory needs of this cohort. Meat intakes in the older
      population are commonly reduced because the relatively tough texture of meat can
      impair mastication. In this study, beef steaks tenderized with papain and papain:
      bromelain (50:50) were demonstrated to produce more tender meat products, with a
      lower cook loss compared with tenderization with bromelain alone, which has
      relevance to the development of texture-optimized meat products that appeal to
      older adults with difficulty in mastication. This information could help meat
      processors to develop strategies for optimization of texture-modified beef
      products within their own businesses.

PMID- 29068046
TI  - GPR35 mediates lodoxamide-induced migration inhibitory response but not CXCL17
      induced migration stimulatory response in THP-1 cells; is GPR35 a receptor for
      CXCL17?
AB  - BACKGROUND AND PURPOSE: GPR35 has long been considered an orphan GPCR, because no
      endogenous ligand of GPR35 has been discovered. CXCL17 (a chemokine) has been
      reported to be an endogenous ligand of GPR35, and it has even been suggested that
      it be called CXCR8. However, at present there is no supporting evidence that
      CXCL17 does interact with GPR35. EXPERIMENTAL APPROACH: We applied two assay
      systems to explore the relationship between CXCL17 and GPR35. An AP-TGF-alpha
      shedding assay in GPR35 over-expressing HEK293 cells was used as a gain-of
      function assay. GPR35 knock-down by siRNA transfection was performed in
      endogenously GPR35-expressing THP-1 cells. KEY RESULTS: In the AP-TGF-alpha
      shedding assay, lodoxamide, a well-known synthetic GPR35 agonist, was confirmed
      to be the most potent agonist among other reported agonists. However, neither
      human nor mouse CXCL17 had an effect on GPR35. Consistent with previous findings,
      G proteins Galphai/o and Galpha12/13 were found to couple with GPR35.
      Furthermore, lodoxamide-induced activation of GPR35 was concentration-dependently
      inhibited by CID2745687 (a selective GPR35 antagonist). In endogenously GPR35
      expressing THP-1 cells, lodoxamide concentration-dependently inhibited migration
      and this inhibitory effect was blocked by CID2745687 treatment or GPR35 siRNA
      transfection. However, even though CXCL17 stimulated the migration of THP-1
      cells, which is consistent with a previous report, this stimulatory effect of
      CXCL17 was not blocked by CID2745687 or GPR35 siRNA. CONCLUSIONS AND
      IMPLICATIONS: The present findings suggest that GPR35 functions as a migration
      inhibitory receptor, but CXCL17-stimulated migration of THP-1 cells is not
      dependent on GPR35.

PMID- 29068049
TI  - The safety and efficacy of powered intracapsular tonsillectomy in children: A
      meta-analysis.
AB  - OBJECTIVES: We performed a systemic review and meta-analysis regarding the
      postoperative pain, perioperative, and postoperative morbidity of powered
      intracapsular tonsillectomy and adenoidectomy (PITA) using a microdebrider as a
      method of tonsillectomy. DATA SOURCES: Five databases (PubMed, Scopus, Embase,
      Web of Science, and the Cochrane Central Register of Controlled Trials) in their
      entirety through March 2017. REVIEW METHODS: We included studies in which there
      was a comparison between groups of patients who underwent PITA (PITA group) and
      those who had extracapsular tonsillectomy (control group). Articles assessing
      effects of PITA in the pediatric patient were systemically and independently
      reviewed by two researchers. The outcomes of interest were intraoperative
      morbidity (operative time and bleeding), postoperative morbidity (postoperative
      pain, recovery time, tonsil regrowth, and postoperative bleeding rate), and
      improvement of sleep breath disorder (apnea-hypopnea index [AHI] and symptomatic
      scores). RESULTS: PITA did not significantly increase operative time or
      intraoperative blood loss. With PITA, there was significantly decreased
      postoperative pain, amount of analgesia, time to resumption of normal diet and
      activity, and incidence of postoperative admissions (due to dehydration or
      postoperative bleeding control) compared to those of the control group. In
      contrast, the incidence of postoperative tonsil regrowth was statistically higher
      in the PITA group than in the control group. The PITA improved AHI and
      obstructive sleep apnea 18-item questionnaire scores significantly, which were
      similar with the control group. CONCLUSIONS: With regard to intraoperative
      morbidity and postoperative morbidity, PITA is a safe procedure. However, there
      are high levels of heterogeneity with regard to several measured parameters.
      Therefore, further large, well-designed trials are required to substantiate our
      findings. Laryngoscope, 128:732-744, 2018.

PMID- 29068050
TI  - Nose blowing after endoscopic sinus surgery does not adversely affect outcomes.
AB  - OBJECTIVE: Patients frequently are advised to abstain from nose blowing following
      endoscopic sinus surgery (ESS), despite a lack of evidence supporting this
      recommendation. This randomized study assessed whether nose blowing in the first
      postoperative week affects subjective and objective clinical outcomes. METHODS:
      Forty patients undergoing ESS were randomized into an interventional arm in which
      patients blew their nose at least twice daily for the first 7 postoperative days,
      or a control arm in which patients refrained from nose blowing. All patients were
      allowed to blow their nose after 7 days. The frequency and degree of epistaxis
      was documented by daily diary and visual analog scale (VAS). At 1 and 4 weeks
      postoperatively, Nasal Obstruction Symptom Evaluation (NOSE) and Sino-Nasal
      Outcome Test-22 (SNOT-22) were collected, and endoscopies were recorded for
      blinded Lund-Kennedy scale scoring. RESULTS: There were no differences between
      the two groups in terms of frequency and duration of bleeding events, VAS
      epistaxis scores, SNOT-22 scores, and NOSE scores at every postoperative
      timepoint. Lund-Kennedy scores also were similar at the 1-week (P = 0.0762) and 4
      week (P = 0.2340) postoperative visits, but the nose-blowing group had improved
      nasal discharge subscores at the first (P = 0.0075) and second (P = 0.0298)
      postoperative visits. CONCLUSION: Nose blowing after ESS does not appear to
      measurably improve symptoms of nasal congestion or general sinonasal quality of
      life, nor does it seem to adversely affect the frequency or severity of
      postoperative epistaxis during the first postoperative week. Judicious nose
      blowing may be permissible immediately after uncomplicated ESS. LEVEL OF
      EVIDENCE: 1b. Laryngoscope, 128:1268-1273, 2018.

PMID- 29068051
TI  - Health disparities among adults with voice problems in the United States.
AB  - OBJECTIVE: To assess differences in access to care and healthcare utilization
      among adults who reported voice problems in 2012. STUDY DESIGN: Cross-sectional
      study. METHODS: The 2012 National Health Interview Survey was utilized to
      evaluate adults who had a "voice problem in the past 12 months." Multivariate
      analyses determined the influence of sociodemographic variables on the prevalence
      of voice problems in adults and access to care. RESULTS: Among 243 million adults
      in the United States, 17.9 +/- 0.05 million adults (7.63% +/- 0.21%) report
      experiencing voice problems. After controlling for age, education, income level,
      geographic region, and health insurance status, African Americans (odds ratio
      [OR]: 0.83, P < 0.05), Hispanics (OR: 0.61, P < 0.01), and other minorities (OR:
      0.69, P < 0.01) had a lower OR for reporting voice problems in the last year
      relative to white adults. Among adults with voice problems, Hispanics were more
      likely to delay care because they could not reach a medical office by telephone
      (OR: 1.85, P < 0.01) and due to long wait times at the doctor's office (OR: 2.04,
      P < 0.01) compared to white adults. Adults with voice problems who were a racial
      minority, low income, or had public health insurance were more likely to postpone
      care because they lacked a mode of transportation. CONCLUSION: Targeted programs
      are necessary to address the health disparities and barriers to care among those
      who suffer from voice problems. LEVEL OF EVIDENCE: IV. Laryngoscope, 128:915-920,
      2018.

PMID- 29068052
TI  - Direct estimate of the spontaneous germ line mutation rate in African green
      monkeys.
AB  - Here, I provide the first direct estimate of the spontaneous mutation rate in an
      Old World monkey, using a seven individual, three-generation pedigree of African
      green monkeys. Eight de novo mutations were identified within ~1.5 Gbp of
      accessible genome, corresponding to an estimated point mutation rate of 0.94 * 10
      8 per site per generation, suggesting an effective population size of ~12000 for
      the species. This estimation represents a significant improvement in our
      knowledge of the population genetics of the African green monkey, one of the most
      important nonhuman primate models in biomedical research. Furthermore, by
      comparing mutation rates in Old World monkeys with the only other direct
      estimates in primates to date-humans and chimpanzees-it is possible to uniquely
      address how mutation rates have evolved over longer time scales. While the
      estimated spontaneous mutation rate for African green monkeys is slightly lower
      than the rate of 1.2 * 10-8 per base pair per generation reported in chimpanzees,
      it is similar to the lower range of rates of 0.96 * 10-8 -1.28 * 10-8 per base
      pair per generation recently estimated from whole genome pedigrees in humans.
      This result suggests a long-term constraint on mutation rate that is quite
      different from similar evidence pertaining to recombination rate evolution in
      primates.

PMID- 29068053
TI  - The role of temporal intervals on reinforcer accumulation.
AB  - Animals accumulate reinforcers when they forgo the opportunity to consume
      available food in favor of acquiring additional food for later consumption.
      Laboratory research has shown that reinforcer accumulation is facilitated when an
      interval (either spatial or temporal) separates earning from consuming
      reinforcers. However, there has been no systematic investigation on the interval
      separating consuming reinforcers from earning additional reinforcers. This
      oversight is problematic because this second interval is an integral part of much
      of the previous research on reinforcer accumulation. The purpose of the current
      study was to determine the independent contributions of these two temporal
      intervals on reinforcer accumulation in rats. Each left lever press earned a
      single food pellet; delivery of the accumulated pellet(s) occurred upon a right
      lever press. Conditions varied based on the presence of either an intertrial
      interval (ITI) that separated pellet delivery from the further opportunity to
      accumulate more pellets, or a delay-to-reinforcement that separated the right
      lever press from the delivery of the accumulated pellet(s). Delay and ITI values
      of 0, 5, 10 and 20 s were investigated. The delay-to-reinforcement conditions
      produced greater accumulation relative to the ITI conditions, despite
      accumulation increasing the density of reinforcement more substantially in the
      ITI conditions. This finding suggests that the temporal separation between
      reinforcer accumulation and subsequent delivery and consumption was a more
      critical variable in controlling reinforcer accumulation.

PMID- 29068054
TI  - Life history and ecology of the elusive European short-snouted seahorse
      Hippocampus hippocampus.
AB  - To improve the understanding of the life history and ecology of one of Europe's
      most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data
      from wild populations in a shallow coastal lagoon in southern Portugal were
      analysed. The data were collected from 17 tagged seahorses on a focal-study grid
      as well as from >350 seahorses encountered during underwater visual surveys and a
      fishery-independent study using beach seines. These populations of settled
      juveniles and adults had a mean population density of 0.009 m-2 . During the
      study period (2000-2004), reproduction peaked in July and August. Juveniles
      recruited to the lagoon at c. 66 mm standard length (LS ) and 0.5 years of age
      and established small home ranges (0.8 to 18.2 m2 ). First reproduction was
      estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model,
      H. hippocampus grew quickly (growth coefficient K = 0.93) to a maximum
      theoretical size Linfinity  = 150 mm and have a maximum lifespan of c. 3.2 years.
      Courtship behaviours were consistent with the maintenance of pair bonds and males
      brooded multiple batches of young per year. Estimated annual reproductive output
      averaged 871 young (+/-632). Together these analyses provide the first life
      history parameters for this species and indicate that H. hippocampus bears
      characteristics of opportunist and intermediate strategists. Such populations are
      predicted to exhibit large fluctuations in abundance, making them vulnerable to
      extended periods of poor recruitment.

PMID- 29068055
TI  - Polypeptoid polymers: Synthesis, characterization, and properties.
AB  - Polypeptoids, a class of peptidomimetic polymers, have emerged at the forefront
      of macromolecular and supramolecular science and engineering as the technological
      relevance of these polymers continues to be demonstrated. The chemical and
      structural diversity of polypeptoids have enabled access to and adjustment of a
      variety of physicochemical and biological properties (eg, solubility, charge
      characteristics, chain conformation, HLB, thermal processability, degradability,
      cytotoxicity and immunogenicity). These attributes have made this synthetic
      polymer platform a potential candidate for various biomedical and
      biotechnological applications. This review will provide an overview of recent
      development in synthetic methods to access polypeptoid polymers with well-defined
      structures and highlight some of the fundamental physicochemical and biological
      properties of polypeptoids that are pertinent to the future development of
      functional materials based on polypeptoids.

PMID- 29068056
TI  - Effect of heavy water on the conformational stability of globular proteins.
AB  - It is well established from the experimental point of view that the native state
      of globular proteins is more stable in heavy water than in water. No robust
      explanation, however, has been provided up to now. The application of the
      theoretical approach, originally devised to rationalize the general occurrence of
      cold denaturation, indicates that the magnitude of the solvent-excluded volume
      effect is slightly smaller in heavy water than in water and cannot explain the
      observed protein stabilization. The latter has to be due to the strength of
      protein-water van der Waals attractions which are weaker in heavy water due to
      the smaller molecular polarizability of D2 O compared with that of H2 O
      molecules. Since protein-water van der Waals attractions occur more in the
      denatured than in the native state, this contribution leads to a stabilization of
      the latter through a destabilization of the former.

PMID- 29068057
TI  - Exploring the influence of hyperthermophilic protein Ssh10b on the stability and
      conformation of RNA by molecular dynamics simulation.
AB  - The hyperthermophilic Ssh10b from Sulfolobus shibatae is a member of the Sac10b
      family, which binds RNA in vivo as a physiological substrate, and it has been
      postulated to play a key role in chromosomal organization in Archaea. Even though
      the crystal structure of Ssh10b-RNA was resolved successively by X-ray
      diffraction (Protein Data Bank [PDB] code: 3WBM), the detailed dynamic
      characteristics of Ssh10b-RNA are still unclear. In this study, molecular
      dynamics (MDs) simulations at 6 temperatures (300, 350, 375, 400, 450, and 500 K)
      and molecular mechanics Generalized-Born surface area (MM-GB/SA) free energy
      calculations were performed to investigate the mechanism of how Ssh10b protects
      and stabilizes RNA. The simulation results indicate that RNA is stabilized by
      Ssh10b when the temperature rises up to 375 K. RNA is found to undergo
      conformational transition between A-RNA and A'-RNA when Ssh10b binds to RNA at 3
      different temperatures (300, 350, and 375 K). Salt bridges, hydrogen bonds and
      hydrophobic interactions are observed, and some residues have significant impact
      on the structural stability of the complex. This study increases our
      understanding of the dynamics and interaction mechanism of hyperthermophilic
      proteins and RNA at the atomic level, and offers a model for studying the
      structural biology of hyperthermophilic proteins and RNA.

PMID- 29068059
TI  - Recent progress of retroauricular robotic thyroidectomy with the new surgical
      robotic system.
AB  - OBJECTIVE: Previously, we have reported the feasibility of retroauricular (RA)
      robotic thyroidectomy. Despite its promising surgical outcomes, there were
      certain intrinsic mechanical limitations inherent to the da Vinci Si System
      (Intuitive Surgical, Sunnyvale, California, U.S.A.). Since the advent of an
      upgraded model, the Xi System (Intuitive Surgical), we have actively incorporated
      the new model into performing RA thyroidectomy. Here, we intend to verify the
      feasibility of RA robotic thyroidectomy using the new da Vinci Xi System
      (Intuitive Surgical) with comparison of the former Si-applied surgery (Intuitive
      Surgical). STUDY DESIGN: Comparative analysis. METHODS: There were total 165
      consecutive patients who received RA robotic thyroidectomy from January 2013 to
      February 2016. The patients were divided into two groups: Si group (n = 125) and
      Xi group (n = 40). Perioperative and treatment outcomes were compared and
      analyzed. RESULTS: Compared with the previous system, new da Vinci Xi system
      (Intuitive Surgical) enabled insertion of an extra third robotic instrumental
      arm. Unlike the previous robotic surgical technique, the robotic dissection could
      be initiated immediately after the establishment of working space and the
      resulting total operation time could be significantly decreased. There was no
      difference in the surgical completeness, as confirmed by postoperative
      thyroglobulin levels. Additionally, flexed EndoWrist (Intuitive Surgical)
      instruments equipped with the Erbe (Erbe USA Inc., Marietta, Georgia, U.S.A.)
      system could be mounted, which further facilitated the operation. There were no
      significant differences in postoperative complications between the two groups.
      CONCLUSION: The RA robotic thyroidectomy with the new Xi System (Intuitive
      Surgical) can greatly facilitate the robotic surgery with comparable or improved
      surgical outcomes. Its application is expected to open up a new era of robotic
      neck surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1730-1737, 2018.

PMID- 29068060
TI  - Parvalbumin interneurons in the dorsal horn: it's not all about GABA.

PMID- 29068058
TI  - Defining a standard and weighted mathematical index for maturation of dendritic
      cells.
AB  - The concept of dendritic cell (DC) maturation generally refers to the changes in
      morphology and function of DCs. Conventionally, DC maturity is based on three
      criteria: loss of endocytic ability, gain of high-level capacity to present
      antigens and induce proliferation of T cells, and mobility of DCs toward high
      concentrations of CCL19. Impairment of DC maturation has been suggested as the
      main reason for infectivity or chronicity of several infectious agents. In the
      case of hepatitis C virus, this has been a matter of controversy for the last two
      decades. However, insufficient attention has been paid to the method of ex vivo
      maturation as the possible source of such controversies. We previously reported
      striking differences between DCs matured with different methods, so we propose
      the use of a standard quantitative index to determine the level of maturity in
      DCs as an approach to compare results from different studies. We designed and
      formulated a mathematically calculated index to numerically define the level of
      maturity based on experimental data from ex vivo assays. This introduces a
      standard maturation index (SMI) and weighted maturation index (WMI) based on
      strictly standardized mean differences between different methods of generating
      mature DCs. By calculating an SMI and a WMI, numerical values were assigned to
      the level of maturity achieved by DCs matured with different methods. SMI and WMI
      could be used as a standard tool to compare diversely generated mature DCs and so
      better interpret outcomes of ex vivo and in vivo studies with mature DCs.

PMID- 29068061
TI  - Home environmental influences on children's language and reading skills in a
      genetically sensitive design: Are socioeconomic status and home literacy
      environment environmental mediators and moderators?
AB  - This twin study examined how family socioeconomic status (SES) and home literacy
      environment (HLE) contributes to Chinese language and reading skills. It included
      312 Chinese twin pairs aged 3 to 11. Children were individually administered
      tasks of Chinese word reading, receptive vocabulary and reading-related cognitive
      skills, and nonverbal reasoning ability. Information on home environment was
      collected through parent-reported questionnaires. Results showed that SES and HLE
      mediated shared environmental influences but did not moderate genetic influences
      on general language and reading abilities. Also, SES and HLE mediated shared
      environmental contributions to receptive vocabulary and syllable and rhyme
      awareness, but not orthographic skills. The findings of this study add to past
      twin studies that focused on alphabetic languages, suggesting that these links
      could be universal across languages. They also extend existing findings on SES
      and HLE's contributions to reading-related cognitive skills.

PMID- 29068062
TI  - Primary chondro-osseous melanoma (chondrosarcomatous and osteosarcomatous
      melanoma).
AB  - Melanoma can rarely show malignant chondro-osseous differentiation and can cause
      diagnostic confusion. We report 3 cases of primary melanoma with extensive bone
      and cartilage matrix. The first case arose in the nasal mucosa of a 72-year-old
      woman, the second case in the left index finger of a 26-year-old woman and the
      third case in the left cheek of a 68-year-old woman. In tumors where osseous and
      chondroid differentiation appear in mucosa and skin, primary melanoma with
      chondro-osteosarcomatous differentiation should be considered in the
      differential. Careful histological examination together with clinical correlation
      and ancillary immunohistochemical studies can ensure the correct diagnosis is
      made.

PMID- 29068063
TI  - CyHV-2 transmission in traded goldfish stocks in Germany-A case study.

PMID- 29068064
TI  - Familial acanthosis nigricans with p.K650T FGFR3 mutation.
AB  - Acanthosis nigricans (AN) is a pigmentary skin disorder, which may present in
      association with clinical disorders such as obesity and malignancy. Occasionally,
      this unique skin manifestation is seen in alliance with several skeletal
      disorders, such Crouzon syndrome, achondroplasia and hypochondroplasia (HCH).
      These orthopedic disorders are known to have genetic changes in FGFR3. Recently,
      AN was reported in HCH with p.K650T mutation in FGFR3, and to date, there are
      only three reports, comprising 18 cases, describing AN harboring this specific
      gene mutation. Herein, we detail three new cases of AN with p.K650T FGFR3
      mutation, and review the 21 known cases.

PMID- 29068065
TI  - Establishment of a cell line from the kidney of black carp and its susceptibility
      to spring viremia of carp virus.
AB  - In this study, we established and characterized a cell line derived from the
      kidney of black carp (Mylopharyngodon piceus), which is an important freshwater
      aquaculture species. The cell line was designated as MPK and subcultured for more
      than 70 passages in DMEM medium containing 10% fetal bovine serum (FBS) at 28
      degrees C. MPK had a modal diploid chromosome number of 48. Moreover, a transient
      MPK transfection efficiency was up to 18% using a green fluorescent protein
      plasmid by a modified electroporation. In addition, the MPK cells showed
      susceptibility to spring viremia of carp virus (SVCV), as demonstrated by the
      presence of severe cytopathic effects (CPEs) and increased viral RNA.
      Unexpectedly, the MPK cells expressed pluripotency-associated genes such as
      nanog, oct4 and vasa, indicating that these are possibly adult stem cells. Taken
      together, we have established a stable cell line from kidney that may potentially
      be utilized as an in vitro platform for genetic modifications and host-pathogen
      analysis in black carp.

PMID- 29068067
TI  - Cryptococcal cellulitis: A rare entity histologically mimicking a neutrophilic
      dermatosis.
AB  - Cutaneous Cryptococcus infection presents classically with granulomatous and
      gelatinous reactive patterns. Cases mimicking neutrophilic dermatoses have not
      been described. Conversely, neutrophilic dermatoses with degrading cells
      mimicking cryptococcal organisms have been reported. We report a case of
      cryptococcal cellulitis in an immunocompromised male with a robust neutrophilic
      infiltrate raising histologic consideration for a neutrophilic dermatosis.

PMID- 29068066
TI  - Parenteral bilirubin in healthy volunteers: a reintroduction in translational
      research.
AB  - AIMS: Preclinical results suggest therapeutic potential of mild
      hyperbilirubinemia in T2DM and cardiovascular disease. Translational data are
      limited, because an appropriate bilirubin formulation for parenteral human use is
      lacking. Considering its use in both clinical practice and medical research in
      the past, we explored the feasibility to reintroduce parenteral bilirubin for
      translational experiments. METHODS: We developed a preparation method in
      accordance with good manufacturing practice and evaluated the parenteral
      applicability in healthy volunteers (n = 8). Explorative pharmacokinetic and
      safety data were compared to the results from a literature study on the former
      parenteral use of bilirubin. Bilirubin was administered intra-arterially to raise
      the local plasma concentration in the forearm vascular bed (n = 4) and
      intravenously to raise the systemic plasma concentration (n = 4). Finally,
      pharmacokinetic characteristics were studied following a single bolus infusion (n
      = 3). RESULTS: During parenteral application, no side effects occurred. Adverse
      events mentioned during the two-week observation period were in general mild and
      self-limiting. Three more significant adverse events (appendicitis, asymptomatic
      cardiac arrhythmia and atopic eczema) were judged unrelated by independent
      physicians. A dose-concentration relationship appeared sufficiently predictable
      for both intra-arterial and intravenous administration. In line with existing
      knowledge, bilirubin pharmacokinetics could be described best according to a two
      compartment model with a volume of distribution of 9.9 (+/-2.0) l and a total
      plasma clearance of 36 (+/-16) ml per minute. CONCLUSIONS: Supported by previous
      reports, our data suggest that it is both feasible and safe to perform
      translational experiments with parenteral albumin bound bilirubin.

PMID- 29068068
TI  - Late-stage nodular erythema elevatum diutinum mimicking sclerotic fibroma.
AB  - Erythema elevatum diutinum (EED) is a rare, cutaneous vasculitis of uncertain
      origin. EED can present clinically as chronic bilateral, symmetrical,
      periarticular papules, plaques and nodules. We report here an unusual case of EED
      presenting as multiple, densely fibrosing nodules on the feet of a 60-year-old
      human immunodeficiency virus positive woman. The initial evaluation of the
      patient was complicated by the strong histologic resemblance of multiple lesions
      to sclerotic fibroma, a cutaneous manifestation of Cowden disease. Our case
      highlights the important features that distinguish these 2 pathologic entities.

PMID- 29068069
TI  - Childhood Abuse, the Interpersonal-Psychological Theory of Suicide, and the
      Mediating Role of Depression.
AB  - Although childhood abuse is a well-known risk factor for suicide, no studies have
      investigated the role of interpersonal-psychological (Joiner, 2005), constructs
      in this association. This study examined whether childhood physical, sexual, and
      emotional abuse were associated with IPTS constructs, and whether depressive
      symptoms mediated these associations. Ninety-one participants completed self
      report measures. Emotional abuse predicted perceived burdensomeness and thwarted
      belongingness, and depressive symptoms mediated these associations. Physical
      abuse predicted the acquired capability for suicide, although depression did not
      mediate this association. These findings suggest that specific types of abuse
      differentially predict IPTS components and underscore depression as a potential
      mechanism.

PMID- 29068071
TI  - Development of the muscles associated with the mandibular and hyoid arches in the
      Siberian sturgeon, Acipenser baerii (Acipenseriformes: Acipenseridae).
AB  - The skeleton of the jaws and neurocranium of sturgeons (Acipenseridae) are
      connected only through the hyoid arch. This arrangement allows considerable
      protrusion and retraction of the jaws and is highly specialized among ray-finned
      fishes (Actinopterygii). To better understand the unique morphology and the
      evolution of the jaw apparatus in Acipenseridae, we investigated the development
      of the muscles of the mandibular and hyoid arches of the Siberian sturgeon,
      Acipenser baerii. We used a combination of antibody staining and formalin-induced
      fluorescence of tissues imaged with confocal microscopy and subsequent three
      dimensional reconstruction. These data were analyzed to address the identity of
      previously controversial and newly discovered muscle portions. Our results
      indicate that the anlagen of the muscles in A. baerii develop similarly to those
      of other actinopterygians, although they differ by not differentiating into
      distinct muscles. This is exemplified by the subpartitioning of the m. adductor
      mandibulae as well as the massive m. protractor hyomandibulae, for which we found
      a previously undescribed portion in each. The importance of paedomorphosis for
      the evolution of Acipenseriformes has been discussed before and our results
      indicate that the muscles of the mandibular and the hyoid may be another example
      for heterochronic evolution.

PMID- 29068070
TI  - Geometric morphometric analysis as a proxy to evaluate age-related change in
      molar shape variation of low-crowned Notoungulata (Mammalia).
AB  - Shape and age variation in dentition of Paleogene extinct native South American
      ungulates (Notoungulata) has been traditionally described using qualitative and
      quantitative approaches, and has played a controversial role in the systematics
      of several groups. Such is the case of the Notopithecidae, a group of
      notoungulates with low-crowned teeth, known from the middle Eocene of Patagonia
      (Argentina). In this group, as well as in other contemporary families, extreme
      morphological changes associated to increasing dental wear were originally
      assumed to represent taxonomic differences; thus, dozens of species were erected,
      clearly reflecting the difficulty of defining discrete characters. In this
      contribution, a total of 89 upper molars and 91 lower molars were analyzed
      distributed in two factors, wear and species; three species of notopithecids were
      considered as study case, Notopithecus adapinus, Antepithecus brachystephanus,
      and Transpithecus obtentus, based on the large and well-identified sample of
      upper and lower molars for each species. We have coupled geometric morphometric
      analyses with traditional comparative methods to get a better understanding and
      interpretation of both the changes in tooth shape contour and the link between
      shape and ontogeny. In addition, we evaluate the utility of this approach to
      identify which changes are strictly wear-related and also test the qualitative
      characteristics used for diagnosing and differentiating notopithecid species. Our
      study yielded consistent results when applying independent geometric morphometric
      analyses on complex structures such as brachydont molar teeth. The landmark data
      is highly congruent with alternative sources of evidence, such as morphological
      studies using discrete characters. In notopithecid species, wear is the main
      factor affecting molar shape, followed by species (in lower molars) and
      allometry; in addition, lower teeth morphology is more definitive in separating
      species than upper molars, a fact that entails a key point for systematic studies
      of Paleogene brachydont notoungulates.

PMID- 29068072
TI  - Twenty-four Segment Transverse Ventricular Fractional Shortening: A New Technique
      to Evaluate Fetal Cardiac Function.
AB  - OBJECTIVES: Because of various fetal and maternal disease states, this study was
      conducted to evaluate the fractional shortening of 24 transverse segments
      distributed from the base to the apex of the ventricular chambers. METHODS: Two
      hundred control fetuses were examined between 20 and 40 weeks' gestation. The
      transverse displacement of the ventricular endocardium during the cardiac cycle
      was computed by using offline software. From the output of the analysis, 24 end
      diastolic and end-systolic segments were measured from the base (segment 1) to
      the apex (segment 24) of the right and left ventricles, and the fractional
      shortening was computed: [(end-diastolic length - end-systolic length)/end
      diastolic length] * 100. Examples of fetal cardiovascular abnormalities were
      selected to demonstrate the utility of this technique. RESULTS: The fractional
      shortening for each segment was independent of gestational age and fetal
      biometric measurements. There was no significant difference in fractional
      shortening for segments 1 to 5 between the right and left ventricles. However,
      the fractional shortening of the left ventricle was significantly greater (P <
      .0001) than that of the right ventricle for segments 6 to 24, suggesting that the
      mid and apical segments of the left ventricle have increased displacement toward
      the center of the chamber compared to the right ventricle. Fetuses with various
      cardiac structural abnormalities had abnormal fractional shortening values.
      CONCLUSIONS: The fractional shortening of 24 segments of the right and left
      ventricles provides a comprehensive method to examine the contractility of the
      ventricular chambers.

PMID- 29068073
TI  - Clinicopathological analysis of myxoid proximal-type epithelioid sarcoma.
AB  - Proximal-type epithelioid sarcoma (ES) with a diffuse myxoid stroma is rare.
      Here, we report the case of a 33-year-old man with a perineal mass. Imaging
      showed the presence of a poorly demarcated 6.9 * 5.3-cm mass in the subcutaneous
      perineal region. Macroscopic examination showed that the resected tissues were
      partially necrotic. Histological examination showed that the tumor comprised
      numerous large or pleomorphic epithelioid cells with large vesicular nuclei and
      prominent nucleoli. A clear background of necrosis and inflammatory exudates was
      also present. Immunohistochemical examination showed that the tumor cells were
      positive for vimentin and CD34 - both of which were expressed throughout the
      cytoplasm - but typically did not express nuclear INI1 (SMARCB1). Hematoxylin
      eosin staining (HE staining) showed that the mucin content of the tumor was
      approximately 80%. The patient was diagnosed with proximal-type ES with myxoid
      features. The patient died due to disease progression after 2 months of follow-up
      and without undergoing further treatment in our department. To our knowledge,
      only 2 cases of proximal-type ES with diffuse myxoid stroma have been reported.
      Proximal-type ES is rare, and this is the first case report of proximal ES with
      myxoid features in the perineal area.

PMID- 29068074
TI  - The anterior process of the malleus in extant Lagomorpha (Mammalia).
AB  - The anterior anchoring of the malleus of 30 extant species of Lagomorpha
      (rabbits, hares, pikas) has been studied on the basis of histological serial
      sections and uCT-scans. It is shown that former studies of Oryctolagus, Lepus,
      and Ochotona are incomplete, because the rostral part of the processus anterior
      of the malleus is always lacking due to damage of this extremely delicate
      structure. Our study shows that in perinatal stages of Leporidae the
      praearticulare develops a prominent processus internus that fits into a groove at
      the ventral side of the tegmen tympani; this "tongue and groove"-arrangement may
      act as a hinge. In adult stages, the rostral end of the praearticulare fuses
      synostotically with the medial process of the ectotympanic. Torsional strain
      produced by rotation around the axis of the middle ear ossicles at sound
      transmission must, therefore, be experienced by the extremely thin but highly
      elastic bony pedicle of the processus internus praearticularis. The free ending
      processus anterior of a late fetal Ochotona shows a short processus internus
      praearticularis, which does not articulate with the tegmen tympani. During
      postnatal development the middle ear of Ochotona becomes considerably remodelled:
      not only does excessive pneumatization of the tegmen tympani and tympanic cavity
      wall occur, but the short processus anterior is fused synostotically to a bone
      trabecula of the tegmen tympani meshwork. The thin and elastic bone bridges are
      not equivalent in Leporidae and Ochotonidae, that is, they must have evolved
      convergently. Fleischer's classification with Oryctolagus possessing a "freely
      mobile type" of middle ear ossicles cannot be supported by our observations. The
      same holds true for Ochotona, which does not represent a "freely mobile type"
      either. Thus, we suggest for the lagomorph middle ear ossicles a new category:
      the "bone elasticity type."

PMID- 29068075
TI  - Histomorphometric approach to differentiate skin lesions of tuberculoid leprosy
      from sarcoidosis.
AB  - BACKGROUND: More than 200 000 new cases of leprosy are detected worldwide
      annually. Physicians commonly have difficulty in differentiating tuberculoid form
      of leprosy (TL) from sarcoidosis' cutaneous manifestation. METHODS: Skin biopsies
      of 33 patients with TL and 24 with sarcoidosis were reviewed on hematoxylin and
      eosin- and Gomori-stained sections, in order to find reliable criteria for
      distinguishing one disease from another. RESULTS: Nine of the 24 features
      analyzed presented significant predictive value for diagnosis (P < .05).
      Predominance of tuberculoid granulomas in adnexal and neural distribution, and
      granulomas replacing the nerves localized within sweat gland glomeruli were
      predictive to TL diagnosis. For sarcoidosis, dermal fibrosis, back-to-back
      distribution of the granulomas, presence of atypical giant cells and plasma
      cells, greater number of conventional giant cells, and spared nerves beside the
      granuloma were predictive criteria. The median surface density of reticulin
      fibers was significantly higher in sarcoidosis (3.44) than in TL (2.99).
      Nonetheless, using logistic regression, this variable did not discriminate
      between the diseases (P = .096). CONCLUSIONS: Isolated histological features are
      not fully predictive to differentiate the 2 diseases. However, those with
      statistical value can assist this distinction in diagnostic practice. Although
      the results of the analysis of the reticulin fibers density did not tell apart TL
      from sarcoidosis, they corroborate the idea of fiber fragmentation within
      tuberculoid leprosy granulomas, reiterating the importance of morphometry in the
      histological examination.

PMID- 29068076
TI  - EMG-Based Estimation of Limb Movement Using Deep Learning With Recurrent
      Convolutional Neural Networks.
AB  - A novel model based on deep learning is proposed to estimate kinematic
      information for myoelectric control from multi-channel electromyogram (EMG)
      signals. The neural information of limb movement is embedded in EMG signals that
      are influenced by all kinds of factors. In order to overcome the negative effects
      of variability in signals, the proposed model employs the deep architecture
      combining convolutional neural networks (CNNs) and recurrent neural networks
      (RNNs). The EMG signals are transformed to time-frequency frames as the input to
      the model. The limb movement is estimated by the model that is trained with the
      gradient descent and backpropagation procedure. We tested the model for
      simultaneous and proportional estimation of limb movement in eight healthy
      subjects and compared it with support vector regression (SVR) and CNNs on the
      same data set. The experimental studies show that the proposed model has higher
      estimation accuracy and better robustness with respect to time. The combination
      of CNNs and RNNs can improve the model performance compared with using CNNs
      alone. The model of deep architecture is promising in EMG decoding and
      optimization of network structures can increase the accuracy and robustness.

PMID- 29068078
TI  - Communication between healthcare professionals and parents is a key factor in
      involving parents in neonatal intensive care.

PMID- 29068077
TI  - Leiomyosarcoma of the great saphenous vein (vena saphena magna) with granular
      cell change: Report of a superficial neoplasm.
AB  - The great saphenous vein (GSV) corresponds to the main superficial large-caliber
      vessel affected by leiomyosarcoma (LMS). Given its superficial location and
      because signs of vascular origin may not be clinically apparent, LMS of the GSV
      may be misinterpreted clinically as superficial nonvascular soft tissue mass.
      Herein, we report a case on the distal portion of the right GSV of a 57-year-old
      man. The histopathological recognition of a large-caliber vein-associated LMS
      (with granular cell change) in an incisional biopsy specimen was crucial to guide
      radiological evaluation and confirmation of a superficial vascular LMS before
      surgical treatment. Recognizing this entity in small biopsies is important as its
      surgical treatment and prognosis differ substantially from nonvascular
      superficial (ie, subcutaneous and dermal) LMSs. In addition, because vascular
      LMSs can involve long vessel segments, underestimation of extent of disease is a
      risk. To the best of our knowledge, granular cell change has not been documented
      in LMS of the GSV.

PMID- 29068079
TI  - Visually enhanced education and immunization perceptions in low-income parents.
AB  - OBJECTIVE: Despite immunizations being an effective health promotion
      intervention, about 28% of children are not up-to-date on the combined seven
      vaccine series by 35 months of age in the United States. Identifying innovative
      techniques to increase immunization literacy is crucial to the health and well
      being of children. DESIGN AND SAMPLE: Based on the theory of multimedia learning,
      this study examined whether the use of visually enhanced education (VEE)
      positively impacted parental perception of immunization effectiveness, perceived
      knowledge of disease, comfort with immunization decision making, and satisfaction
      with the provider. Forty parents of infants 4-14 days old that could read
      English. INTERVENTION: Parents completed a questionnaire with 12 items in four
      categories during the initial visit (4-14 days old) before VEE and at the second
      visit (17-37 days later) after the second VEE session had been completed.
      RESULTS: A paired sample t test revealed a significant increase in two of the
      four categories (i.e., perceived knowledge of the disease [t(37) = 8.73, p =
      .000] and satisfaction with the provider [t(37) = 2.68, p = .011]. Cohen's effect
      size value suggested high practical significance in one of the four categories
      (i.e., perceived knowledge of disease d = 1.31, d = 1.42, d = 1.18, d = 1.05, d =
      1.12). Cronbach's alpha for the 12 items was 0.852. CONCLUSIONS: VEE may be an
      innovative technique for improving parental immunization health literacy and
      increasing parent-professional communication about immunizations.

PMID- 29068080
TI  - Electrothermal enrichment of submicron particles in an insulator-based
      dielectrophoretic microdevice.
AB  - Insulator-based dielectrophoresis (iDEP) exploits in-channel hurdles and posts
      etc. to create electric field gradients for various particle manipulations.
      However, the presence of such insulating structures also amplifies the Joule
      heating in the fluid around themselves, leading to both temperature gradients and
      electrothermal flow. These Joule heating effects have been previously
      demonstrated to weaken the dielectrophoretic focusing and trapping of microscale
      and nanoscale particles. We find that the electrothermal flow vortices are able
      to entrain submicron particles for a localized enrichment near the insulating
      tips of a ratchet microchannel. This increase in particle concentration is
      reasonably predicted by a full-scale numerical simulation of the mass transport
      along with the coupled charge, heat and fluid transport. Our model also predicts
      the electric current and flow pattern in the fluid with a good agreement with the
      experimental observations.

PMID- 29068081
TI  - A New Pressure Guided Management Tool for Epidural Space Detection: Feasibility
      Assessment on a Simulator.
AB  - The detection of epidural space is usually performed by the technique of loss of
      resistance (LOR) without technological support, although there are few commercial
      options. We sought to design and develop a new noninvasive system able to detect
      the LOR without any changes to the conventional procedure. It allows detecting
      the LOR by a custom made algorithm. The system provides a visual and acoustic
      feedback when the LOR is detected. We optimized the detection algorithm and
      investigated the performance of the system during experiments on a custom
      simulator. During the experiments performed by 10 anesthetists and 10 trainees,
      the pressure exerted on the syringe plunger was monitored using the custom-made
      system. Each participant performed four experiments using the system on the
      simulator. The performance of the system in LOR detection was evaluated comparing
      the feedback activation and the breaches of the last layer of the simulator.
      Moreover, each participant filled out a questionnaire to assess how the procedure
      with the simulator mimics the clinical scenario. A higher questionnaire score
      corresponds to a more realistic condition (0 = not real, 5 = extremely real).
      Results showed that the LOR was detected in 74 of the 80 trials (92.5% of the
      cases); the anesthetists obtained better results than trainees: 97.5 versus
      87.5%. The questionnaires showed that all the participants found the trial
      realistic (score >=3); anesthetists found it more realistic than trainees (4.2 +/
      0.78 vs. 3.8 +/- 0.78, mean +/- SD). In summary, the proposed system
      successfully detected the LOR in the large part of the trials. The participants
      found the trials realistic. A higher success rate was observed in the
      anesthetists group.

PMID- 29068082
TI  - Successful treatment of relapsed folliculotropic mycosis fungoides with
      mogamulizumab followed by intensity-modulated radiotherapy.

PMID- 29068083
TI  - Threats to biodiversity from cumulative human impacts in one of North America's
      last wildlife frontiers.
AB  - Land-use change is the largest proximate threat to biodiversity yet remains one
      of the most complex to manage. In British Columbia (BC), where large mammals roam
      extensive tracts of intact habitat, continued land-use development is of global
      concern. Extant mammal diversity in BC is unrivalled in North America owing, in
      part, to its unique position at the intersection of alpine, boreal, and temperate
      biomes. Despite high conservation values, understanding of cumulative ecological
      impacts from human development is limited. Using cumulative-effects-assessment
      (CEA) methods, we assessed the current human footprint over 16 regional
      ecosystems and 7 large mammal species. Using historical and current range
      estimates of the mammals, we investigated impacts of human land use on species'
      persistence. For ecosystems, we found that bunchgrass, coastal Douglas fir, and
      ponderosa pine have been subjected to over 50% land-use conversion, and over 85%
      of their spatial extent has undergone either direct or estimated indirect
      impacts. Of the mammals we considered, wolves were the least affected by land
      conversion, yet all species had reduced ranges compared with historical
      estimates. We found evidence of a hard trade-off between development and
      conservation, most clearly for mammals with large distributions and ecosystems
      with high levels of conversion. Rather than serve as a platform to monitor
      species decline, we strongly advocate these data be used to inform land-use
      planning and to assess current conservation efforts. More generally, CEAs offer a
      robust tool to inform wildlife and habitat conservation at scale.

PMID- 29068084
TI  - Regional incidences of adult T-cell leukemia/lymphoma with cutaneous involvement
      in Japan.
AB  - Between 2008 and 2015, 462 newly-diagnosed adult T-cell leukemia/lymphoma (ATLL)
      patients with cutaneous involvement were found from the nationwide registry for
      Japanese patients with cutaneous lymphoma, of which 391 were selected for the
      study. They ranged in age from 28 to 93 years (median, 69 years), and included
      215 men and 176 women (male : female ratio = 1.2). The 391 patients comprised 193
      (50%) with smoldering type, 52 (13%) with chronic type, 44 (11%) with lymphoma
      type and 102 (26%) with acute type. The total number of patients in
      Kyushu/Okinawa was 8.8-times higher than that in Kanto, which was set as the
      reference value, while the estimated prevalence of human T-lymphotropic virus 1
      (HTLV-1) carriers in Kyushu/Okinawa has been reported to be only 2.5-times higher
      than that in Kanto. In this study, the annual incidence of ATLL per 100 000
      residents in Kyushu/Okinawa was 32-times higher than that in Kanto. Our results
      indicated the higher incidence rate of ATLL in the endemic area than those in the
      non-endemic areas in Japan, compared with the regional differences of HTLV-1
      prevalence determined by serological HTLV-1 screening for blood donors. In
      addition, this analysis revealed that regional differences of mycosis
      fungoides/Sezary syndrome incidence rates were very small compared with those of
      ATLL.

PMID- 29068085
TI  - "Chondroblastoma-like" epithelioid fibrous histiocytoma: A previously undescribed
      and potentially confusing variant.
AB  - BACKGROUND: Epithelioid benign fibrous histiocytoma has been considered a variant
      of fibrous histiocytoma, but is now considered a distinct entity, typically
      showing ALK expression. Most show typical morphological features, including an
      epidermal collarette and large, bland, epithelioid cells. We have recently
      encountered 2 examples showing an unusual pattern of pericellular calcification,
      a previously unreported finding. METHODS: Available slides were reviewed and
      clinical follow-up was obtained. RESULTS: These lesions occurred on the chins of
      a 16-year-old and 19-year-old female and showed prominent pericellular
      calcification in addition to otherwise-typical features of epithelioid fibrous
      histiocytoma. By immunohistochemistry, both lesions were intensely positive for
      ALK protein. Clinical follow-up (available for 1 case) showed the patient to be
      disease-free 5 months after excision. CONCLUSIONS: To the best of our knowledge,
      epithelioid fibrous histiocytomas showing "chondroblastoma-like" calcification
      have not been previously reported. The chief significance of this finding seems
      to be in its potential for confusion with other calcifying tumors of the skin and
      subcutis. Awareness that epithelioid fibrous histiocytomas may show this unusual
      morphological finding, careful morphological evaluation and ancillary
      immunohistochemical studies, including ALK protein, should allow for their
      confident diagnosis in essentially all instances.

PMID- 29068086
TI  - Novel KRT9 missense mutation in a Japanese case of epidermolytic palmoplantar
      keratoderma.

PMID- 29068087
TI  - Dramatic effect of hydroxychloroquine on lupus alopecia.
AB  - Lupus alopecia is usually difficult to treat. We report a case of a 40-year-old
      woman with Sjogren's syndrome and atopic dermatitis who presented with discoid
      lupus erythematosus on the forearms and lupus erythematosus profundus with
      alopecia involving the scalp. A biopsy specimen taken from the discoid lupus
      erythematosus lesion on the forearm further exhibited a xanthomatous reaction,
      which however was not detected in another specimen from the lupus erythematosus
      profundus on the scalp. Treatment with oral hydroxychloroquine showed dramatic
      effects and complete hair regrowth was obtained 3 months later.

PMID- 29068088
TI  - Mechanisms of lysophosphatidylcholine-induced demyelination: A primary lipid
      disrupting myelinopathy.
AB  - For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce
      demyelination, without a clear understanding of its mechanisms. LPC is an
      endogenous lysophospholipid so it may cause demyelination in certain diseases. We
      investigated whether known receptor systems, inflammation or nonspecific lipid
      disruption mediates LPC-demyelination in mice. We found that LPC nonspecifically
      disrupted myelin lipids. LPC integrated into cellular membranes and rapidly
      induced cell membrane permeability; in mice, LPC injury was phenocopied by other
      lipid disrupting agents. Interestingly, following its injection into white
      matter, LPC was cleared within 24 hr but by five days there was an elevation of
      endogenous LPC that was not associated with damage. This elevation of LPC in the
      absence of injury raises the possibility that the brain has mechanisms to buffer
      LPC. In support, LPC injury in culture was significantly ameliorated by albumin
      buffering. These results shed light on the mechanisms of LPC injury and
      homeostasis.

PMID- 29068089
TI  - Application of hydrolysis probe analysis to identify clade types of the malaria
      vector mosquito Anopheles funestus sensu stricto from Muheza, northeastern
      Tanzania.
AB  - A hydrolysis probe analysis (TaqMan assay) was used to study clade types in
      Anopheles funestus sensu stricto Giles, a major malaria vector in sub-Saharan
      Africa, with specimens collected from Muheza in Tanga, northeastern Tanzania. A
      total of 186 An. funestus specimens were analysed, revealing that 176 (94.6%)
      were of clade I and 10 (5.4%) of clade II. These findings extend the distribution
      of clade type II from southern Mozambique and northern Zambia to northeastern
      Tanzania. The technique used can also be of great value in assessing the role and
      contribution of these clade types in malaria transmission and insecticide
      resistance frequencies for An. funestus s.s.

PMID- 29068090
TI  - Early introduction of allergenic foods for the prevention of food allergy from an
      Asian perspective-An Asia Pacific Association of Pediatric Allergy, Respirology &
      Immunology (APAPARI) consensus statement.
AB  - Emerging evidence for the early introduction of allergenic foods for the
      prevention of food allergies, such as peanut allergy in Western populations, has
      led to the recent publication of guidelines in the USA and Europe recommending
      early peanut introduction for high-risk infants with severe eczema or egg
      allergy. Peanut allergy is, however, much less prevalent in Asia compared to the
      West. Varying patterns of food allergy are seen even within Asian countries-such
      as a predominance of wheat allergy in Japan and Thailand and shellfish allergy in
      Singapore and the Philippines. Customs and traditions, such as diet and infant
      feeding practices, also differ between Asian populations. Hence, there are unique
      challenges in adapting guidelines on early allergenic food introduction to the
      Asian setting. In this paper, we review the evidence and discuss the possible
      approaches to guide the timely introduction of allergenic food in high-risk
      infants in Asia.

PMID- 29068091
TI  - A Serratia marcescens outbreak in a neonatal intensive care unit was successfully
      managed by rapid hospital hygiene interventions and screening.
AB  - AIM: Serratia marcescens is a rare, but important, pathogen in hospital-acquired
      infections, especially in neonatal units. Outbreaks may cause significant
      mortality among neonates. This study describes how an outbreak of S. marcescens
      was handled in a neonatal intensive care unit in Finland in June 2015. METHODS:
      Tampere University Hospital is the only hospital that offers intensive care for
      preterm neonates in the Pirkanmaa health district area in Finland. Between June
      9, 2015 and June 29, 2015, seven neonates were screened positive for S.
      marcescens in the hospital. We examined the management and outcomes, including
      environmental sampling. RESULTS: Two of the seven neonates developed a
      bloodstream infection, and one with S. marcescens sepsis died after six days of
      antibiotic treatment. The outbreak was rapidly managed with active hospital
      hygiene interventions, including strict hand hygiene, cleaning, patient
      screening, contact precautions and education. Environmental sampling was limited
      to one water tap and a ventilator, and the results were negative. The outbreak
      was contained within three weeks, and no further cases appeared. The screening of
      healthcare workers was not necessary. CONCLUSION: A S. marcescens outbreak caused
      significant morbidity in neonates and one death. Rapid hospital hygiene
      interventions and patient screening effectively contained the outbreak.

PMID- 29068092
TI  - High-dose mizoribine combined with calcineurin inhibitor (cyclosporine or
      tacrolimus), basiliximab and corticosteroids for renal transplantation: A
      Japanese multicenter study.
AB  - OBJECTIVE: To evaluate the utility and safety of high-dose mizoribine combination
      therapy using cyclosporine and tacrolimus as calcineurin inhibitors in patients
      undergoing kidney transplant. METHODS: The present study enrolled 156 patients
      who received kidney transplants in 18 institutions between 2009 and 2013. ABO
      incompatible and/or pre-sensitized recipients were excluded. Immunosuppression
      used cyclosporine (88) or tacrolimus (68) as a calcineurin inhibitor, and the
      dosage was adjusted based on blood concentrations. Mizoribine was started at 6
      mg/kg/day, and the target trough level was 1-2 ng/mL. Primary efficacy end-points
      of this study were 2-year patient survival, 2-year graft survival and the acute
      rejection rate within 2 years after transplantation. RESULTS: The 2-year patient
      and graft survival rates in the cyclosporine group were 98.9% and 94.3%,
      respectively, whereas those in the tacrolimus group were 100% and 98.5%,
      respectively, with no significant difference between groups. Rates of onset of
      rejection during the observation period were also equivalent, at 22.7% in the
      cyclosporine group and 17.6% in the tacrolimus group. Furthermore, groups showed
      no significant differences in transplanted renal function. No notable differences
      in adverse events were observed between groups. CONCLUSIONS: A regimen of high
      dose mizoribine in combination with calcineurin inhibitors basiliximab, and
      corticosteroids can provide effective immunosuppression while lowering the rate
      of cytomegalovirus infection in kidney transplant patients.

PMID- 29068093
TI  - On Pentakis(pentafluoroethyl)stannate, [Sn(C2 F5 )5 ]- , and the Gas-Free
      Generation of Pentafluoroethyllithium, LiC2 F5.
AB  - Pentafluoroethyllithium, LiC2 F5 , has been established as an efficient and
      versatile reagent for the transfer of the pentafluoroethyl unit to a number of
      electrophiles. Here, the stability of this species up to -40  degrees C is of
      advantage, particularly in comparison to its smaller congener LiCF3 . The usual
      production of LiC2 F5 , however, from gaseous HC2 F5 or IC2 F5 and strong bases
      requires specially designed apparatuses, which severely impeded its value as a
      laboratory reagent. In this contribution we communicate an alternative gas-free
      and highly efficient protocol for the synthesis of LiC2 F5 from the already
      commercialized stannate salt [PPh4 ][Sn(C2 F5 )5 ]. The [Sn(C2 F5 )5 ]- anion
      represents not only the first example of a structurally characterized hypervalent
      pentaalkylstannate but also serves as a precursor for the synthesis of the
      homoleptic tetrakis(pentafluoroethyl)stannane, Sn(C2 F5 )4 . The reaction of the
      latter with n-butyllithium provides an insight into the mechanism of LiC2 F5
      generation.

PMID- 29068094
TI  - Kinematic cross-correlation induces sensory integration across separate objects.
AB  - In a basic cursor-control task, the perceived positions of the hand and the
      cursor are biased towards each other. We recently found that this phenomenon
      conforms to the reliability-based weighting mechanism of optimal multisensory
      integration. This indicates that optimal integration is not restricted to sensory
      signals originating from a single source, as is the prevailing view, but that it
      also applies to separate objects that are connected by a kinematic relation (i.e.
      hand and cursor). In the current study, we examined which aspects of the
      kinematic relation are crucial for eliciting the sensory integration: (i) the
      cross-correlation between kinematic variables of the hand and cursor
      trajectories, and/or (ii) an internal model of the hand-cursor kinematic
      transformation. Participants made out-and-back movements from the centre of a
      semicircular workspace to its boundary, after which they judged the position
      where either their hand or the cursor hit the boundary. We analysed the position
      biases and found that the integration was strong in a condition with high
      kinematic correlations (a straight hand trajectory was mapped to a straight
      cursor trajectory), that it was significantly reduced for reduced kinematic
      correlations (a straight hand trajectory was transformed into a curved cursor
      trajectory) and that it was not affected by the inability to acquire an internal
      model of the kinematic transformation (i.e. by the trial-to-trial variability of
      the cursor curvature). These findings support the idea that correlations play a
      crucial role in multisensory integration irrespective of the number of sensory
      sources involved.

PMID- 29068096
TI  - Challenges on-the-way of nursing administration at public hospitals in Kabul,
      Afghanistan.
AB  - PURPOSE: The purpose of this study was to determine the challenges faced by the
      nursing administration at public hospitals in Kabul, Afghanistan. METHODS: A
      cross-sectional study design was used to recruit 86 nursing managers and head
      nurses from 17 public hospitals in Kabul. The participants rated the frequency of
      13 challenges that hinder their performance. RESULTS: There were 14 nursing
      managers and 72 head nurses in the study. Almost 80% of the participants were
      male with the majority falling in the 35-44 year age bracket. Both nursing
      managers and head nurses were equally affected by all 13 challenges, except the
      lack of recognition where head nurses were affected more than the nursing
      managers (p = .003). The most frequent challenges for both were staff absenteeism
      and then too many responsibilities. CONCLUSION: There are multiple challenges
      that hinder the performance of nursing administration that need to be addressed
      through appropriate national policy and strategies. IMPLICATIONS FOR NURSING
      MANAGEMENT: The findings of this study can inform policy makers and draw their
      attention to overcome the challenges faced by nursing management. This will
      ultimately improve satisfaction leading to improved patient and organisational
      outcome. The national policy and strategy should address areas that could enable
      nurses to maintain a balance between household and professional responsibilities;
      and also encourage the enrolment of female nurses in the profession.

PMID- 29068097
TI  - Antimicrobial Peptide Structures: From Model Membranes to Live Cells.
AB  - The rise in antibiotic resistance has led to a renewed interest in antimicrobial
      peptides (AMPs) that target membranes. The mode of action of AMPs involves the
      disruption of the lipid bilayer and leads to growth inhibition and death of the
      bacteria. However, details at the molecular level of how these peptides kill
      bacteria and the reasons for the observed differences in selectivity remain
      unclear. Structural information is crucial for defining the molecular mechanism
      by which these peptides recognize, self-assemble and interact with a particular
      lipid membrane. Solid-state NMR is a non-invasive technique that allows the study
      of the structural details of lipid-peptide and peptide-peptide interactions.
      Following on from studies of antibiotic and lytic peptides, gramicidin A and
      melittin, respectively, we investigated maculatin 1.1, an AMP from the skin of
      Australian tree frogs that acts against Gram-positive bacteria. By using
      perdeuterated phospholipids and specifically labelled peptides, 2 H, 31 P and {31
      P}15 N REDOR solid-state NMR experiments have been used to localize, maculatin
      1.1 in neutral and anionic model membranes. However, the structure, location and
      activity depend on the composition of the model membrane and current advances in
      solid-state NMR spectroscopy now allow structure determination of AMPs in live
      bacteria.

PMID- 29068098
TI  - Dynamical response properties of neocortical neurons to conductance-driven time
      varying inputs.
AB  - Ensembles of cortical neurons can track fast-varying inputs and relay them in
      their spike trains, far beyond the cut-off imposed by membrane passive electrical
      properties and mean firing rates. Initially explored in silico and later
      demonstrated experimentally, investigating how neurons respond to sinusoidally
      modulated stimuli provides a deeper insight into spike initiation mechanisms and
      information processing than conventional F-I curve methodologies. Besides net
      membrane currents, physiological synaptic inputs can also induce a stimulus
      dependent modulation of the total membrane conductance, which is not reproduced
      by standard current-clamp protocols. Here, we investigated whether rat cortical
      neurons can track fast temporal modulations over a noisy conductance background.
      We also determined input-output transfer properties over a range of conditions,
      including: distinct presynaptic activation rates, postsynaptic firing rates and
      variability and type of temporal modulations. We found a very broad signal
      transfer bandwidth across all conditions, similar large cut-off frequencies and
      power-law attenuations of fast-varying inputs. At slow and intermediate input
      modulations, the response gain decreased for increasing output mean firing rates.
      The gain also decreased significantly for increasing intensities of background
      synaptic activity, thus generalising earlier studies on F-I curves. We also found
      a direct correlation between the action potentials' onset rapidness and the
      neuronal bandwidth. Our novel results extend previous investigations of dynamical
      response properties to non-stationary and conductance-driven conditions, and
      provide computational neuroscientists with a novel set of observations that
      models must capture when aiming to replicate cortical cellular excitability.

PMID- 29068095
TI  - Mnemonic and attentional roles for states of attenuated alpha oscillations in
      perceptual working memory: a review.
AB  - Alpha oscillations are often reported to be amplified during working memory (WM)
      retention, serving to disengage sensory areas to protect internal representations
      from external interference. At the same time, contemporary views of WM postulate
      that sensory areas may often also be recruited for retention. I here review
      recent evidence that during such 'perceptual' WM, alpha oscillations in
      mnemonically relevant sensory areas are not amplified but attenuated instead. I
      will argue that such attenuated alpha states serve a mnemonic role and, further,
      that larger attenuation may support item-specific attentional prioritisation
      within perceptual WM. In critically evaluating this role, I also consider (and
      argue against) four alternatives to a strictly mnemonic account of the available
      data that may also prove useful to consider in future research. Finally, I
      highlight key implications of these data for the study of WM and for our
      understanding of the functional roles of states of attenuated alpha oscillations
      in cognition.

PMID- 29068099
TI  - Subcutaneous administration of ciclosporin in 11 allergic cats - a pilot open
      label uncontrolled clinical trial.
AB  - BACKGROUND: Oral ciclosporin has been reported to be efficacious for feline
      inflammatory skin diseases; however, cats are often difficult to medicate orally.
      HYPOTHESIS/OBJECTIVE: To evaluate the efficacy and tolerability of subcutaneous
      ciclosporin administered to cats with allergic skin disease. ANIMALS: Eleven
      client-owned cats with nonseasonal clinical signs. METHODS: Prospective open
      label trial. Ciclosporin 50 mg/mL solution for injection (Sandimune(r), Novartis;
      NJ, USA) was administered subcutaneously for 60 days with initial doses ranging
      from 2.5 mg/kg once daily (one cat) to every other day (five cats) and 5 mg/kg
      once daily (four cats) to every other day (one cat). Dosages were adjusted
      monthly if needed based on clinical response. Clinical response was assessed
      using a modified FeDESI (feline Dermatitis Extent and Severity Index) and PVAS
      (pruritus Visual Analog Scale) between days (D) 0, 30 and 60. RESULTS: Six cats
      completed the study and four of five cats withdrawn from the study were included
      in an intention-to-treat analysis. There was significant decrease in FeDESI and
      PVAS scores between D0 and D30, D0 and D60 and D30 and D60 (P < 0.05) in all ten
      cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Ciclosporin administered
      subcutaneously at initial doses of 2.5-5 mg/kg, once daily to alternate days,
      appears to be an efficacious therapy for feline allergic dermatitis and may be an
      alternative therapy for cats that cannot be treated orally. Randomized and
      controlled long term studies which include a larger number of cats are needed to
      confirm these findings.

PMID- 29068102
TI  - 2-(Trimethylsilyl)-lambda3 -Phosphinine: Synthesis, Coordination Chemistry, and
      Reactivity.
AB  - The [4+2] cycloaddition reaction between 2-pyrone and Me3 Si-C=P gives the
      corresponding 2-(trimethylsilyl)-lambda3 -phosphinine in good yields as a rather
      air and moisture stable, colorless oil. Insight into the regioselectivity of the
      pericyclic reaction was obtained with the help of deuterium-labeling experiments.
      The silyl-phosphinine acts as a ligand for the preparation of a Cu(I) and the
      first crystallographically characterized phosphinine-Ag(I) complex. The title
      compound was further used as a starting material for an alternative preparation
      of the parent phosphinine C5 H5 P by means of protodesilylation with HCl. C5 H5 P
      reacts with CuBr?S(CH3 )2 to give an infinite Cu(I)Br coordination polymer. DFT
      calculations shed light on the influence of the -Si(CH3 )3 group on the
      electronic properties of the aromatic phosphorus heterocycle.

PMID- 29068101
TI  - Isolation and characterization of human mesenchymal stem cells derived from
      synovial fluid by magnetic-activated cell sorting (MACS).
AB  - Mesenchymal stem cells (MSCs) are the primary source of cells used for cell-based
      therapy in tissue engineering. MSCs are found in synovial fluid, a source that
      could be conveniently used for cartilage tissue engineering. However, the
      purification and characterization of SF-MSCs has been poorly documented in the
      literature. Here, we outline an easy-to-perform approach for the isolation and
      culture of MSCs derived from human synovial fluid (hSF-MSCs). We have
      successfully purified hSF-MSCs using magnetic-activated cell sorting (MACS) using
      the MSC surface marker, CD90. Purified SF-MSCs demonstrate significant renewal
      capacity following several passages in culture. Furthermore, we demonstrated that
      MACS-sorted CD90+ cells could differentiated into osteoblasts, adipocytes, and
      chondrocytes in vitro. In addition, we show that these cells can generate
      cartilage tissue in micromass culture as well. This study demonstrates that MACS
      is a useful tool that can be used for the purification of hSF-MSCs from synovial
      fluid. The proliferation properties and ability to differentiate into
      chondrocytes make these hSF-MSCs a promising source of stem cells for
      applications in cartilage repair.

PMID- 29068100
TI  - Upregulated osterix expression elicited by Runx2 and Dlx5 is required for the
      accelerated osteoblast differentiation in PP2A Calpha-knockdown cells.
AB  - Serine/threonine protein phosphatase 2A (PP2A) is involved in regulating various
      physiological processes including cell cycle, growth, apoptosis, and signal
      transduction. Osteoblast differentiation is controlled by main bone specific
      transcription factors including Osterix, distal-less homeobox 5 (Dlx5), and Runt
      related transcription factor 2 (Runx2). We previously reported that knockdown of
      PP2A Calpha increases the expression of Osterix, leading to the accelerated
      osteoblast differentiation through the upregulation of bone-related genes. In
      this study, we examined whether Dlx5 and Runx2 are involved in the upregulated
      Osterix expression in PP2A Calpha-knockdown osteoblasts (shPP2A cells). The
      expression of Dlx5 as well as Osterix was significantly higher in shPP2A cells in
      the initial stage of osteoblast differentiation compared with the control cells
      (shCont). The expression of Runx2 protein was also higher in shPP2A cells
      compared with shCont cells although its mRNA level was comparable. Reduction of
      Dlx5 or Runx2 decreased Osterix expression and alkaline phosphatase activity in
      shPP2A cells. Luciferase assay showed that Osterix promoter activity was
      drastically elevated in shPP2A cells compared with that in shCont cells. The
      deletion or mutation of the Dlx5 and Runx2 binding sites significantly suppressed
      Osterix promoter activity in shPP2A cells. These results indicate that Dlx5 and
      Runx2 are critical factors for the upregulated Osterix expression in shPP2A
      cells, which is considered to be important for the accelerated osteoblast
      differentiation in these cells.

PMID- 29068103
TI  - Desipramine-induced lysosomal vacuolization is independent of autophagy.
AB  - Desipramine, a commonly used antidepressant drug, induced cytosolic vacuolization
      in L929 cells. The level of LC3-II was elevated and that of p62 was reduced in
      desipramine-treated L929 cells, indicating the induction of autophagy by
      desipramine. Surprisingly, massive vacuolization was observed in desipramine
      treated L929 cells in the presence of LY294002, an inhibitor of autophagy. On the
      other hand, bafilomycin A1, an inhibitor of vacuolar type H+ ATPase, almost
      completely inhibited vacuolization in desipramine- or desipramine/LY294002
      treated L929 cells. Furthermore, desipramine-induced vacuolization was observed
      in autophagy-deficient Atg7-/- mouse embryonic fibroblasts (MEFs) as well as wild
      type Atg7+/+ MEFs. These results demonstrate that desipramine-induced lysosomal
      vacuolization is independent of autophagy.

PMID- 29068104
TI  - Nitrite-Enhanced Charge Transfer to and from Single Polyaniline Nanotubes.
AB  - As Liu et al. reported previously (Appl. Mater. Today 2017, 7, 239-245), the
      charge transfer to partially oxidized polyaniline (PANI) nanotubes in
      electrochemical reactions is heavily limited due to the non-conductivity of the
      reduction/oxidation products. In this paper, the doping level of individual PANI
      nanotubes was substantially enhanced using nitrite as an electron acceptor in
      sulfuric acid aqueous solution as recorded by the nano-impact method. The charge
      transferred to one single tube during reduction process is close to the
      theoretical value of 170+/-112 pC per tube (assuming 2-electron reduction for the
      PANI tubes studied), while the charge during PANI oxidation is dramatically
      decreased. Reaction processes are proposed based on the oxidative properties of
      nitrite in acid solution. UV-visible spectroscopy analysis further confirms an
      oxidation-reduction reaction between PANI and nitrite. In contrast the
      electrochemical reaction of ensembles (21 MUg cm-1 ) of PANI tubes on glassy
      carbon electrodes simply show limited electrocatalytic activity.

PMID- 29068105
TI  - Mechanism and Origin of the Stereoselectivity in the Palladium-Catalyzed trans
      Hydroboration of Internal 1,3-Enynes with an Azaborine-Based Phosphine Ligand.
AB  - An azaborine-based phosphine-Pd catalyst was introduced by the Liu group to
      promote trans hydroboration of the C=C triple bond of internal 1,3-enyne
      substrates. Despite the excellent yield and selectivity observed experimentally,
      the mechanism and the origin of this special trans selectivity remained unknown.
      Herein, a comprehensive theoretical investigation was performed to clarify these
      issues. Accordingly, two main mechanisms (inner- and outer-sphere) were proposed
      and examined. Different from the conventional inner-sphere mechanism, in which
      the transition metal is involved in H-B bond cleavage, this reaction follows an
      outer-sphere mechanism, in which Pd does not directly participate in H-B bond
      cleavage. More specifically, the favorable pathway followed a Tsuji-Trost type
      reaction, in which the H-B bond was weakened by the formation of a four
      coordinate boron intermediate (i.e., the boron is attached to the terminal carbon
      of the alkyne group). It then underwent a hydride-transfer process with the
      assistance of a second borane molecule, and finally reductive elimination
      generated the trans hydroboration product. Further analysis ascribed the origin
      of the special trans selectivity to the unique steric effect and electronic
      effect introduced by the special kappa1 -P-eta2 -BC coordination pattern.

PMID- 29068106
TI  - Clinical profile of congenital rubella syndrome in Yogyakarta, Indonesia.
AB  - BACKGROUND: Congenital rubella syndrome (CRS) has many severe neurological
      manifestations and other systemic consequences. Although various studies have
      been done in Indonesia, there are no conclusive results on CRS incidence. The aim
      of this study was therefore to investigate the incidence, clinical manifestations
      and outcomes of CRS in Yogyakarta, Indonesia. METHODS: A descriptive study
      involving a review of congenital anomalies associated with CRS was carried out at
      Dr Sardjito Hospital, Yogyakarta, Indonesia, from July 2008 to June 2013. CRS was
      categorized according to the World Health Organization (WHO) classification. This
      study involved children aged <1 year old, and was conducted at the outpatient
      clinic, pediatric and neonatology wards. RESULTS: A total of 201 children met the
      criteria for suspected CRS during the 5 year study. Of those patients, 6% were
      classified as having laboratory-confirmed CRS, 21.4% as having clinically
      compatible CRS, and 72.6% as having discarded CRS (i.e. a suspected case that
      does not meet the criteria for CRS). The estimated incidence of laboratory
      confirmed CRS and laboratory-confirmed and clinically compatible CRS in
      Yogyakarta, Indonesia during the study period was 0.05:1,000 and 0.25:1,000 live
      births, respectively. Of the laboratory-confirmed CRS patients, 83.3% of children
      had congenital heart disease (CHD), 75% had hearing impairment, 66.7% had
      congenital cataract and 50% had microcephaly. Furthermore, none of the mothers
      was vaccinated against rubella. CONCLUSIONS: The incidence of CRS in infants in
      Yogyakarta Indonesia is considered high, with most clinical manifestations being
      CHD, hearing impairment and congenital cataract. This emphasizes the necessity
      for epidemiological study of CRS in other hospitals and the importance of
      establishing a national rubella vaccination program in Indonesia.

PMID- 29068107
TI  - Dinuclear Iron(II) Spin-Crossover Compounds: A Theoretical Study.
AB  - The structures and spin-state energetics of two di-iron(II) complexes based on
      thiadiazole and oxadiazole ligands in different crystals were studied by using
      density functional theory and second-order perturbation theory based on the
      density matrix renormalization group approach (DMRG-CASPT2). When taking into
      account all different contributions to the relative energy, our theoretical
      approach is capable of providing results that are in excellent agreement with
      established experimental data. In all cases, we correctly describe the ground
      state of the complexes as well as predict their spin-crossover behavior. A
      comparison between the two complexes in the gas phase and in different crystals
      shows how the structures change by moving from the gas phase to different
      crystals and reveals a large impact of the crystal stabilization on the relative
      spin-state energy. This theoretical work also demonstrates the applicability of
      the DMRG-CASPT2 approach to quantitatively study the spin-state energetics of
      multinuclear transition-metal complexes.

PMID- 29068108
TI  - Sustained tachyarrhythmia in children younger than 1 year of age: Six year single
      center experience.
AB  - BACKGROUND: The aim of this study was to evaluate the results of non-operational
      sustained tachyarrhythmia in patients <1 year of age at the present center.
      METHODS: Between November 2010 and November 2016, the demographic
      characteristics, type and localization of the tachyarrhythmia, echocardiographic
      findings, and medical and/or ablation therapy for patients <1 year of age with
      sustained tachyarrhythmia were evaluated. RESULTS: Of 99 patients, 91 had
      sustained supraventricular tachycardia, and eight had sustained ventricular
      tachycardia. The median age was 30 days (range, 1-350 days), and the median
      weight was 4.2 kg (range, 2-13 kg). The common symptoms were palpitation and
      restlessness (n = 49, 49.5%), or the tachycardia was detected during routine
      inspection (n = 25, 25.3%) or fetal echocardiography (n = 11, 11.1%). Nineteen
      individuals (19%) had left ventricular (LV) dysfunction on first
      echocardiography. Twenty individuals had congenital heart disease. Common
      diagnoses were Wolff-Parkinson-White syndrome (n = 27), focal atrial tachycardia
      (n = 10), permanent junctional reciprocating tachycardia(n = 6), and atrial
      flutter (n = 6). Seventeen patients underwent medical therapy combined with
      cardioversion. The most commonly used abortive and acute therapy agents were
      adenosine, esmolol, and amiodarone. The most common combination therapy was
      propranolol and amiodarone, followed by a propranolol and propafenone
      combination. Nine individuals were treated with catheter ablation due to either
      resistance to medical therapy or LV dysfunction. CONCLUSIONS: Tachyarrhythmias in
      children <1 year of age are mostly caused by accessory pathways and require
      multidrug therapy. Catheter ablation is an effective alternative therapy in the
      case of resistance to medical therapy and/or LV dysfunction.

PMID- 29068110
TI  - A review of genome-wide transcriptomics studies in Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive and incurable neurodegenerative
      disorder. Although numerous genetic and environmental factors have been linked to
      the aetiology of PD the underlying pathobiology remains poorly understood,
      hampering the development of improved therapies. Transcriptomics has the
      potential to reveal significant insights into disease processes. In this review,
      we focused on published transcriptomics studies on PD with the aim of summarizing
      studies and identifying common biological pathways. A total of 96 articles were
      identified as follows: 12 meta-analyses, 21 re-analyses of existing data and 63
      original studies. Of the 63 original studies, 33 were performed on brain tissue,
      26 on blood, three on cerebrospinal fluid and one on skin. In the brain studies,
      altered pathways identified included those involved in dopamine metabolism,
      mitochondrial function, oxidative stress, protein degradation, neuroinflammation,
      vesicular transport and synaptic transmission. Studies on blood samples revealed
      alterations in pathways involved in immune function, inflammation, RNA
      processing, protein chaperones, mitochondrial function and programmed cell death.
      Limitations of these studies include small sample sizes (generally <40 cases/40
      controls) and the application of widely varying statistical analysis and
      parameters. Only eight studies used the RNA-Seq technique. This review highlights
      the need for harmonization of transcriptomic approaches and the statistical
      analyses, and for the data to be deposited into publicly available databases in a
      standardized format for meta-analyses. Notably, the concordance of several
      pathways such as mitochondrial function, protein degradation and inflammation,
      identified in both blood and brain tissues, suggests that the disease process is
      systemic and not restricted to neurological tissues.

PMID- 29068111
TI  - A Manganese Pre-Catalyst: Mild Reduction of Amides, Ketones, Aldehydes, and
      Esters.
AB  - A new (N-phosphinoamidinate)manganese complex is shown to be a useful pre
      catalyst for the hydrosilative reduction of carbonyl compounds, and in most cases
      at room temperature. The Mn-catalyzed reduction of tertiary amides to tertiary
      amines, with a useful scope, is demonstrated for the first time by use of this
      catalyst, and is competitive with the most effective transition-metal catalysts
      known for such transformations. Ketones, aldehydes, and esters were also
      successfully reduced under mild conditions by using this new Mn catalyst.

PMID- 29068109
TI  - Firefly Luciferin-Inspired Biocompatible Chemistry for Protein Labeling and In
      Vivo Imaging.
AB  - Biocompatible reactions have emerged as versatile tools to build various
      molecular imaging probes that hold great promise for the detection of biological
      processes in vitro and/or in vivo. In this Minireview, we describe the recent
      advances in the development of a firefly luciferin-inspired biocompatible
      reaction between cyanobenzothiazole (CBT) and cysteine (Cys), and highlight its
      versatility to label proteins and build multimodality molecular imaging probes.
      The review starts from the general introduction of biocompatible reactions, which
      is followed by briefly describing the development of the firefly luciferin
      inspired biocompatible chemistry. We then discuss its applications for the
      specific protein labeling and for the development of multimodality imaging probes
      (fluorescence, bioluminescence, MRI, PET, photoacoustic, etc.) that enable high
      sensitivity and spatial resolution imaging of redox environment, furin and
      caspase-3/7 activity in living cells and mice. Finally, we offer the conclusions
      and our perspective on the various and potential applications of this reaction.
      We hope that this review will contribute to the research of biocompatible
      reactions for their versatile applications in protein labeling and molecular
      imaging.

PMID- 29068112
TI  - Use of systemic bivalirudin with catheter-directed thrombolysis in a patient with
      heparin-induced thrombocytopenia: A case report.
AB  - In patients with submassive pulmonary embolism, the use of catheter-directed
      thrombolysis (CDT), using low-dose alteplase is associated with improvement in
      overall hemodynamics. The data for use of CDT in patients with heparin-induced
      thrombocytopenia are limited. We report a case of CDT in a patient with HIT using
      bivalirudin anticoagulation. Data of the use of bivalirudin and argatroban for
      systemic anticoagulation with CDT are limited.

PMID- 29068113
TI  - Surface-Enhanced Raman Spectroscopy Characterization of Salt-Induced Aggregation
      of Gold Nanoparticles.
AB  - Low-frequency (<300 cm-1 ) vibrational interactions between gold surfaces and
      dissolved halides in water were investigated by surface-enhanced Raman
      spectroscopy (SERS). Experiments with NaF, NaCl, NaBr, and NaI salts indicate
      that the Raman shifts of the Au-X- SERS bands correlate with the bond strength of
      the corresponding covalent interaction. These low-frequency SERS bands open up
      new means to investigate the aggregation of nanoparticles in aqueous
      environments.

PMID- 29068114
TI  - Monday 30 October.

PMID- 29068117
TI  - Film Abstracts.

PMID- 29068118
TI  - Past Lecturers and Briefs For the Named Lectures: RANZCO Annual Scientific
      Congress.

PMID- 29068119
TI  - Wednesday 1 November.

PMID- 29068122
TI  - Tuesday 31 October.

PMID- 29068121
TI  - Sunday 29 October.

PMID- 29068123
TI  - Invited Speakers.

PMID- 29068124
TI  - Percutaneous transcatheter aortic valve replacement induces femoral artery
      shrinkage: angiographic evidence and predictors for a new side effect.
AB  - OBJECTIVES: We sought to investigate the possible impact of transaortic valve
      replacement (TAVR) on common femoral artery (CFA) integrity as assessed by
      angiography. BACKGROUND: CFA represents the most adopted access for TAVR but
      various degrees of vascular damage may be induced by the procedure. METHODS:
      Patients underwent percutaneous transfemoral TAVR who had both pre- and post-TAVR
      access-site angiography were retrospectively selected. Clinical and procedural
      data (including technique and complications) were prospectively recorded into a
      structured TAVR database. Pre-TAVR and post-TAVR angiograms were analyzed using a
      quantitative angiographic analysis software to assess reference diameters,
      minimum luminal diameter (MLD), and percentage of diameter stenosis (DS).
      RESULTS: A total of 124 patients entered the study (mean age: 85 years, mean
      Euroscore II: 10%). ProStar (13.5%) and double ProGlide (82.2%) preclosure were
      the main hemostatic techniques. CFA exhibited a significant shrinkage with TAVR
      as assessed by significant MLD reduction (5.6 mm after TAVR vs. 6.8 mm before, P
      < .001) and DS increase (30.3% after vs. 17.0%, P < .001). Such differences
      remained statistically significant after exclusion of 18 patients (14.2%) who had
      (minor or major) vascular complications. At multivariable analysis, pre-TAVR DS
      (P = .03) and history of peripheral arterial disease (P = .01), were
      significantly associated with vascular complications. CONCLUSIONS: Percutaneous
      TAVR induces an angiographically detectable CFA lumen reduction. Such findings
      call for further studies assessing clinical impact of this phenomenon and open
      the door for further refinements of the TAVR access management aimed at
      preserving vessel integrity.

PMID- 29068125
TI  - Novel use of cutting balloon to treat subintimal hematomas during chronic total
      occlusion interventions.
AB  - Contemporary chronic total occlusion (CTO) percutaneous coronary interventional
      (PCI) techniques are increasingly dependent upon dissection and reentry
      techniques (DARTs) especially for long occluded lesions. DARTs can result in
      compressive hematomas during CTO interventions and traditional treatment with
      balloon angioplasty and/or coronary stenting are often suboptimal and may extend
      the hematoma distally. We describe the novel use of a cutting balloon to
      "express" these compressive hematomas and restore antegrade coronary blood flow.

PMID- 29068126
TI  - Impact of subintimal plaque modification procedures on health status after
      unsuccessful chronic total occlusion angioplasty.
AB  - OBJECTIVES: We sought to determine the impact of subintimal plaque modification
      (SPM) on early health status following unsuccessful chronic total occlusion (CTO)
      PCI. BACKGROUND: Intentionally dilating the subintimal space during unsuccessful
      CTO PCI to facilitate flow through dissection planes and improve success of
      repeat PCI attempts is a technique used by some hybrid operators, and may improve
      health status by restoring distal vessel flow despite unsuccessful CTO PCI.
      METHODS: We studied 138 patients who underwent unsuccessful CTO PCI in a 12
      center CTO PCI registry. Safety was assessed by comparing in-hospital outcomes of
      patients undergoing unsuccessful CTO PCI with and without SPM. The association
      between SPM and health status was quantified using the Seattle Angina
      Questionnaire Summary Score (SAQ SS), and the association between SPM and SAQ SS
      was determined using multivariable regression. RESULTS: SPM was performed in 59
      patients (42.8%). Complication rates were similar comparing those with and
      without SPM. At 1-month, patients treated with SPM had larger increases in SAQ SS
      compared to patients who were not (28.3 +/- 21.7 vs. 16.8 +/-20.2, P = 0.012),
      and SPM was associated with an adjusted mean 10.5 point (95% CI 1.4-19.7, P =
      0.02) greater SAQ SS improvement through 30 days. CONCLUSION: SPM was performed
      in almost half of unsuccessful CTO PCIs and was not associated with increased
      procedural complications. SPM was independently associated with better patient
      reported health status at 30 days. Further studies are needed to assess the
      necessity of subsequent PCI in patients with significant health status
      improvements after SPM.

PMID- 29068128
TI  - Percutaneous axillary arteriotomy closure during transcatheter aortic valve
      replacement using the MANTA device.
AB  - Percutaneous aortic valve replacement is performed predominantly via the
      transfemoral approach. The transaxillary (subclavian) approach may be utilized if
      an alternative route access is required. Conventional access and closure for this
      approach necessitates open surgical techniques. We report a nonsurgical fully
      percutaneous axillary TAVR using a collagen-based vascular closure device.

PMID- 29068129
TI  - Bicaval Medtronic Melody valve implantation for treatment of severe mitral
      regurgitation following the Mustard repair: A case report.
AB  - We present a case of successful bicaval Melody valve implantation to treat severe
      mitral regurgitation in a 44-year-old man with d-transposition of the great
      arteries, repaired via a Mustard operation. The patient sustained injury to the
      anterior mitral valve leaflet during laser extraction of a ventricular pacing
      lead resulting in acute, severe, symptomatic mitral regurgitation. The presence
      of systemic venous baffles of similar caliber to right ventricular outflow tract
      conduits allowed for implantation of Melody valves within each baffle. The
      patient remains asymptomatic with excellent Melody valve function 14 months post
      procedure.

PMID- 29068127
TI  - The preventive effects of edible folic acid on cardiomyocyte apoptosis and
      survival in early onset triple-transgenic Alzheimer's disease model mice.
AB  - In recent years, neuropathological and epidemiological studies have indicated an
      association between Alzheimer's disease (AD) and several cardiovascular risk
      factors. In this study, the cardio-protective effects of folic acid (FA) in early
      stage AD was elucidated using a triple-transgenic (3xTg) Alzheimer's mouse model.
      Eleven-month-old C57BL/6 mice and 3xTg mice were assigned to five groups. During
      the four-month treatment period, the low-FA treatment group received FA through
      their diet, and the high-FA treatment groups received 3 mg/dl folate in drinking
      water and were also gastric-fed 1.2 mg/kg folate every day. In the C57B1/6J mice,
      treatment with high doses of FA (HFA) did not show any considerable effect
      compared to the control group or the low-dose dietary FA treatment group.
      However, Alzheimer's mice treated with HFA showed enhanced cardio-protection.
      Western blot analysis revealed that FA treatment restored SIRT1 expression, which
      was suppressed in 3xTg mice, through enhanced AMPK expression. FA significantly
      enhanced the IGF1 receptor survival mechanism in the hearts of the 3xTg mice and
      suppressed the expression-intrinsic and extrinsic apoptosis-associated proteins.
      The results suggest that FA intake may significantly alleviate cellular
      pathological events in the heart associated with AD.

PMID- 29068130
TI  - Clinical outcomes of patients with diabetes mellitus treated with Absorb
      bioresorbable vascular scaffolds: a subanalysis of the European Multicentre GHOST
      EU Registry.
AB  - BACKGROUND: Data on the clinical performance of bioresorbable scaffolds in
      patients with diabetes mellitus (DM) are still limited. The present study
      reported 1-year clinical outcomes associated with the use of everolimus-eluting
      bioresorbable vascular scaffolds (Absorb BVS; Abbott Vascular, Santa Clara, CA)
      in DM patients. METHODS AND RESULTS: This was a subanalysis from the GHOST-EU
      (Gauging coronary Healing with biOresorbable Scaffolding plaTforms in Europe)
      multicenter retrospective registry including patients treated with Absorb BVS
      between November 2011 and September 2014. In this study, a comparative analysis
      stratified according to DM was performed. The primary endpoint was target lesion
      failure (TLF), defined as the combination of cardiac death, target-vessel
      myocardial infarction (MI) and clinically-driven target-lesion revascularization
      (TLR). A total of 1,477 patients were treated with 2,224 Absorb BVS; 381 (25.8%)
      and 1,096 (74.2%) patients were with and without DM, respectively. The 1-year
      rate of TLF was higher among patients with DM (7.8%) than those without DM
      (4.3%); the increase in TLF was driven by TLR (6.5% vs. 3.3%, P = 0.009); no
      significant differences in cardiac death (1.1% vs. 0.9%, P = 0.68) and target
      vessel MI (3.1% vs. 2.2%, P = 0.38) were observed, respectively.
      Definite/probable scaffold thrombosis rate tended to be higher among patients
      with DM than those without DM (3.0% vs. 1.7%, P = 0.14, respectively).
      CONCLUSIONS: Absorb BVS use in patients with DM was associated with increased 1
      year TLF and scaffold thrombosis compared with non-diabetes patients.

PMID- 29068131
TI  - Renal artery stenosis and ambulatory blood pressure monitoring: A case report and
      review of the literature.
AB  - Renal artery stenosis (RAS) is a prevalent cause of secondary hypertension.
      Elderly patients with atherosclerosis and young women with fibromuscular
      dysplasia (FMD) are particularly at risk. Blood pressure screening is often key
      to this diagnosis, although the reliability of clinical screening has been
      questioned, and ambulatory blood pressure monitoring (ABPM) likely offers
      superior ability to diagnose poorly controlled hypertension. In patients with
      RAS, medical management should be the primary means of therapy; however, in a
      select group of these patients, renal revascularization may be considered, and
      has been shown to reduce blood pressure and stabilize chronic kidney disease. In
      this report, we present a patient diagnosed with RAS due to FMD, found to have
      significant hypertension via ABPM, and treated successfully with percutaneous
      renal artery angioplasty; importantly, continuous 24-hr ambulatory monitoring
      after pressure gradient guided renal angioplasty confirmed reduction in blood
      pressure.

PMID- 29068132
TI  - Ostial right coronary chronic total occlusion: Transesophageal echocardiographic
      guidance for retrograde aortic re-entry.
AB  - As antegrade options are limited, intervention upon the ostial right coronary
      artery (RCA) chronic total occlusion (CTO) warrants a retrograde approach.
      Landmarks for an aggressive approach are concerning as passage of stiff
      guidewires or electrocautery near the RCA ostium may result in wire passage into
      structures other than the aorta. We report the first use of transesophageal
      echocardiography (TEE) to assist retrograde passage of a guidewire into the
      aorta. For the ostial RCA CTO, TEE guidance may be considered to assist
      retrograde passage of aggressive guidewires into the aorta.

PMID- 29068133
TI  - Comparison of transcatheter and surgical treatment of paravalvular leak: Results
      from a 5-year follow-up study.
AB  - OBJECTIVE: This study aimed to compare the efficacy and safety of two different
      treatments of paravalvular leak (PVL). BACKGROUND: PVL is a common complication
      after surgical valve replacement. Re-operation is associated with high mortality,
      morbidity, and risk of re-leak. Catheter-based repair has emerged as a promising
      new therapy. METHODS AND RESULTS: Eighty-seven consecutive patients with
      symptomatic PVL received either transcatheter (n = 46) or surgical (n = 41)
      treatment at Shanghai Chest Hospital between January 2009 and December 2015.The
      procedural and clinical success rates were similar between the transcatheter
      group and the surgical group (82.6 vs. 90.2%; P = 0.30; and 69.5 vs. 73.0%; P =
      0.71, respectively). There were fewer in-hospital total major adverse events in
      the transcatheter group (56.09 vs. 17.39%; P < 0.001), and transcatheter repair
      was more cost-effective, with fewer blood transfusions, shorter procedure
      durations, shorter hospital stays, and less expenditure. However, there were six
      cases of hemolysis aggravation in the transcatheter group (13.04%). The 5-year
      overall survival rates after transcatheter and surgical repair were 74.39 and
      71.95% (P = 0.45), respectively, and the cardiac-related survival rates were
      84.08 and 74.72% (P = 0.19), respectively. CONCLUSION: Transcatheter and surgical
      repairs are both effective treatments for selected patients with PVL. And,
      transcatheter closure seems to be safer and more cost-effective. Nonetheless,
      this new treatment may be risky for post-procedure hemolysis when unsuitable
      devices are used.

PMID- 29068134
TI  - Structure, function, and regulation of mitofusin-2 in health and disease.
AB  - Mitochondria are highly dynamic organelles that constantly migrate, fuse, and
      divide to regulate their shape, size, number, and bioenergetic function.
      Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1
      (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in
      these molecules are associated with severe neurodegenerative and non-neurological
      diseases pointing to the importance of functional mitochondrial dynamics in
      normal cell physiology. In recent years, significant progress has been made in
      our understanding of mitochondrial dynamics, which has raised interest in
      defining the physiological roles of key regulators of fusion and fission and led
      to the identification of additional functions of Mfn2 in mitochondrial
      metabolism, cell signalling, and apoptosis. In this review, we summarize the
      current knowledge of the structural and functional properties of Mfn2 as well as
      its regulation in different tissues, and also discuss the consequences of
      aberrant Mfn2 expression.

PMID- 29068135
TI  - A case of bronchopericardial fistula with tension pneumopericardium closed
      successfully by transpericardial intervention: A novel procedure.
AB  - A pneumopericardium is a collection of air or gas in the pericardial sac which
      may cause cardiac tamponade, known as tension pneumopericardium. Tension
      pneumopericardium is a rare and lethal presentation of bronchopericardial
      fistula. There are very few reports in the literature of patients surviving with
      this condition, although prompt diagnosis and early intervention are important.
      Treatment options are limited. We present a rare case of tension
      pneumopericardium with cardiogenic shock due to bronchopericardial fistula in a
      patient with bronchogenic carcinoma who was successfully treated with
      transpericardial intervention.

PMID- 29068136
TI  - Letter to the editor regarding Cevallos PC et al. Radiation dose benchmarks in
      pediatric cardiac catheterization: A prospective multi-center C3P0-QI study.
      Catheter Cardiovasc Interv. 2017 Aug;90(2):269-280.

PMID- 29068137
TI  - Clinical and procedural outcomes with the SAPIEN 3 versus the SAPIEN XT
      prosthetic valves in transcatheter aortic valve replacement: A systematic review
      and meta-analysis.
AB  - OBJECTIVES: The SAPIEN 3 valve (S3V) was designed to overcome the shortcomings of
      its predecessor, the SAPIEN XT (SXT) valve. We conducted a meta-analysis to
      compare their clinical outcomes and procedural characteristics. METHODS: PUBMED,
      EMBASE, and Cochrane CENTRAL were searched by two independent reviewers. The
      clinical outcomes of interest were paravalvular leakage (PVL), major vascular
      complications (MVC), bleeding, acute kidney injury (AKI), device success, need
      for post dilation all-cause mortality and procedural details. RESULTS: Fifteen
      observational cohort studies were included in the analysis involving a total of
      4,496 patients. Of these, 1,700 were S3V recipients and 2,796 were SXT
      recipients. The S3V group showed fewer complications compared to the SXT group
      with respect to PVL (5.58% vs. 19.35%, OR: 0.27, P: 0.000), MVC (4.07% vs. 9.13%,
      OR: 0.44, P: 0.002), bleeding (6.40% vs. 12.03%, OR: 0.50, P: 0.003), 30-day
      mortality (3.29% vs. 5.68%, OR: 0.51, P: 0.000), and stroke (1.48% vs. 2.86%, OR:
      0.49, P: 0.014). Device success was higher in the S3V (98.18% vs. 93.76%, OR:
      3.14, P: 0.000). Cardiovascular mortality, myocardial infarction, AKI and post
      dilatation were not significantly different. Permanent pacemaker implantation
      (PPI) was higher in S3V recipients (13.29% vs. 9.23%, OR: 1.58, P: 0.000).
      Procedure time was shorter for the S3V (71.94 vs. 86.85, P: 0.016) and used less
      contrast volume (129.36 vs. 161.18, P: 0.049). CONCLUSIONS: Patients receiving
      the S3V had lower risk of PVL, MVC, bleeding, mortality, and stroke. PPI was
      somewhat higher in the S3V group. S3V implantation was faster and used less
      contrast.

PMID- 29068138
TI  - High Resolution Mass Spectrometric Analysis of Secoiridoids and Metabolites as
      Biomarkers of Acute Olive Oil Intake-An Approach to Study Interindividual
      Variability in Humans.
AB  - SCOPE: Phenolic compounds are minor components of extra virgin olive oil (EVOO).
      Secoiridoids are the major components contributing to the phenolic content of
      EVOO. Information is lacking regarding their potential as biomarkers for EVOO
      intake. METHODS AND RESULTS: Healthy volunteers (n = 9) ingested 50 mL of EVOO in
      a single dose containing 322 mg kg-1 total phenolic content (caffeic acid
      equivalents) and 6 mg 20 g-1 hydroxytyrosol and its derivatives. Plasma is
      collected before (0 h) and at 0.5, 1, 2, 4, and 6 h after ingestion. Urine
      samples are collected prior to ingestion (0 h) and at 0-4, 4-8, 8-15, and 15-24
      h. Samples are analyzed by UPLC coupled with an Exactive Orbitrap MS. Partial
      least squares discriminant analysis with orthogonal signal correction is applied
      to screen for metabolites that allow sample discrimination. Plasma biomarkers and
      urine biomarkers are selected although individual variability is observed among
      volunteers. Results are in accordance with in vitro experiments performed (in
      vitro digestion and hepatic microsomal activity assays). CONCLUSIONS: Plasma
      (elenolic acid + H2 ; p-HPEA-EA + H2 + glucuronide) and urinary (3,4-DHPEA-EA,
      3,4-DHPEA-EA + H2 +glucuronide, methyl 3,4-DHPEA-EA + H2 +glucuronide)
      secoiridoid compounds are selected as biomarkers to monitor EVOO intake showing
      good predictive ability according to multivariate analysis.

PMID- 29068139
TI  - Comparative study on chemical components and anti-inflammatory effects of Panax
      notoginseng flower extracted by water and methanol.
AB  - Methanol and water are commonly used solvents for chemical analysis and
      traditional decoction, respectively. In the present study, a high-performance
      liquid chromatography with ultraviolet detection method was developed to quantify
      11 saponins in Panax notoginseng flower extracted by aqueous solution and
      methanol, and chemical components and anti-inflammatory effects of these two
      extracts were compared. The separation of 11 saponins, including notoginsenoside
      Fc and ginsenoside Rc, was well achieved on a Zorbax SB C18 column. This
      developed method provides an adequate linearity (r2  > 0.999), repeatability (RSD
      < 4.26%), inter- and intraday variations (RSD < 3.20%) with recovery (94.7
      104.1%) of 11 saponins concerned. Our data indicated that ginsenoside
      biotransformation in PNF was found, when water was used as the extraction
      solvent, but not methanol. Specifically, the major components of Panax
      notoginseng flower, ginsenosides Rb1, Rc, Rb2, Rb3, and Rd, can be near
      completely transformed to the minor components, gypenoside XVII, notoginsenoside
      Fe, ginsenoside Rd2, notoginsenoside Fd, and ginsenoside F2, respectively. Total
      protein isolated from Panax notoginseng flower is responsible for this
      ginsenoside biotransformation. Additionally, methanol extract exerted the
      stronger anti-inflammatory effects than water extract in lipopolysaccharide
      induced RAW264.7 cells. This difference in anti-inflammatory action might be
      attributed to their chemical difference of saponins.

PMID- 29068140
TI  - A founder mutation in CERKL is a major cause of retinal dystrophy in Finland.
AB  - PURPOSE: To study the genetic aetiology of retinal dystrophies (RD) in Finnish
      patients. METHODS: A targeted next-generation sequencing (NGS) panel of 105
      retinal dystrophy genes was used in a cohort of 55 RD patients. RESULTS: The
      overall diagnostic yield was 60% demonstrating the power of this approach.
      Interestingly, a missense mutation c.375C>G p.(Cys125Trp) in the CERKL gene was
      found in 18% of the patients in either a homozygous or compound heterozygous
      state. Data from Exome Aggregation Consortium (ExAC) Browser show that the CERKL
      c.375C>G p.(Cys125Trp) allele is enriched in the Finnish population and thus is a
      founder mutation. Furthermore, we report the clinical picture of 18 patients with
      mutations in the CERKL gene. CERKL mutations cause a macular-onset disease, in
      which symptoms first become apparent at the second decade. We also detected other
      novel founder mutations in the CERKL, EYS, RP1, ABCA4 and GUCY2D genes.
      CONCLUSION: Our report indicates that the first diagnostic test for Finnish
      patients with sporadic or autosomal recessive RD should be a targeted test for
      founder mutations in the CERKL, EYS, RP1, ABCA4 and GUCY2D genes. These results
      confirm the utility of NGS-based gene panels as a powerful method for mutation
      identification in RD, thus enabling improved genetic counselling for these
      families.

PMID- 29068141
TI  - Interventional closure of patent foramen ovale with Nit-occlud(r) device in
      prevention of recurrent neurologic events-Long-term results.
AB  - BACKGROUND: Patent foramen ovale (PFO) was found to be associated with the
      increased risk of recurrent strokes or transient ischemic attacks (TIA) and there
      is a need of secondary prevention. Numerous devices have been developed and used
      for treatment. OBJECTIVES: The aim of the study was to evaluate the safety and
      effectiveness of a new PFO occluder Nit-Occlud? PFO Occlusion Device (PFM
      medical, Germany). METHODS: Between January 2012 and August 2016, 151 patients
      (mean age 41 +/- 11 years) who had suffered from a cryptogenic thromboembolic
      event underwent transcatheter PFO closure with the PFM Nit-Occlud PFO device. The
      procedure was successful in 150 patients (99.3%). Mean clinical follow-up time
      was 24.4 +/- 16.1 months. Echocardiographic follow-up was done at 6 weeks and 6
      months post intervention by transesophageal contrast echocardiography in 90 (60%)
      of patients. Clinical end-point was death, non-fatal stroke, or TIA. RESULTS: No
      major periprocedural or in-hospital complications occurred. Stroke or TIA
      reoccurred generally in 5 (3.3%) patients (2 strokes and 3 TIA's). In one patient
      (0.7%) device, thrombosis was observed. Closure was sufficient with only minimal
      right-to-left residual shunt in seventeen cases of 90 examined patients (19%)
      after 6 weeks and in one patient (1.1%) 6 months post implantation. CONCLUSIONS:
      The Nit-Occlud PFO device and its delivery system are safe and provides
      sufficient closure of PFO in patients who suffered from cryptogenic stroke, TIA
      or paradoxical peripheral embolism. It is associated with high procedural success
      and favorable rates of complete closure.

PMID- 29068142
TI  - Recurrence of oxalate nephropathy after isolated kidney transplantation for
      primary hyperoxaluria type 2.

PMID- 29068143
TI  - Immunoisolation of murine islet allografts in vascularized sites through
      conformal coating with polyethylene glycol.
AB  - Islet encapsulation may allow transplantation without immunosuppression, but thus
      far islets in large microcapsules transplanted in the peritoneal cavity have
      failed to reverse diabetes in humans. We showed that islet transplantation in
      confined well-vascularized sites like the epididymal fat pad (EFP) improved graft
      outcomes, but only conformal coated (CC) islets can be implanted in these sites
      in curative doses. Here, we showed that CC using polyethylene glycol (PEG) and
      alginate (ALG) was not immunoisolating because of its high permselectivity and
      strong allogeneic T cell responses. We refined the CC composition and explored
      PEG and islet-like extracellular matrix (Matrigel; MG) islet encapsulation (PEG
      MG) to improve capsule immunoisolation by decreasing its permselectivity and
      immunogenicity while allowing physiological islet function. Although the
      efficiency of diabetes reversal of allogeneic but not syngeneic CC islets was
      lower than that of naked islets, we showed that CC (PEG MG) islets from fully MHC
      mismatched Balb/c mice supported long-term (>100 days) survival after
      transplantation into diabetic C57BL/6 recipients in the EFP site (750-1000 islet
      equivalents/mouse) in the absence of immunosuppression. Lack of immune cell
      penetration and T cell allogeneic priming was observed. These studies support the
      use of CC (PEG MG) for islet encapsulation and transplantation in clinically
      relevant sites without chronic immunosuppression.

PMID- 29068144
TI  - Branch retinal artery occlusion as a clinical manifestation of hereditary
      haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) in pregnancy.

PMID- 29068145
TI  - Validation of the prognostic power of the RETREAT score for hepatocellular
      carcinoma recurrence using the UNOS database.
AB  - Researchers in a recent multicenter study developed and validated a novel
      prognostic index, Risk Estimation of Tumor Recurrence After Transplant (RETREAT),
      which incorporates alpha-fetoprotein (AFP) at liver transplantation (LT),
      microvascular invasion, and the sum of the largest viable tumor and number of
      tumors on explant. We now aim to evaluate RETREAT in the United Network for Organ
      Sharing (UNOS) database in patients with hepatocellular carcinoma (HCC) who meet
      Milan criteria by imaging and underwent LT between 2012 and -2014. On
      explantation (n = 3276), 13% had microvascular invasion, 30% had no viable tumor,
      and 15% exceeded Milan criteria. Post-LT survival at 3 years decreased with
      increasing RETREAT score: 91% for a score of 0, 80% for a score of 3, and 58% for
      a score >=5 (P < .001). Post-LT HCC recurrence probability within 3 years
      increased from 1.6% with RETREAT score of 0% to 29% for a score >=5 (P < .001).
      Increasing RETREAT score was also associated with a shorter time to HCC
      recurrence. RETREAT was superior to Milan criteria (explant) in predicting HCC
      recurrence by the net reclassification index (P < .001). This study validates the
      prognostic power of RETREAT, which may help standardize post-LT surveillance,
      provide a framework for tumor staging and risk stratification, and select
      candidates for adjuvant therapies.

PMID- 29068146
TI  - Chronic inflammation predicts long-term mortality in patients with Raynaud's
      phenomenon.
AB  - BACKGROUND: Subclinical chronic inflammation could be the driving force behind
      the recently revealed association between abnormal nailfold capillaries as well
      as autoantibodies and long-term mortality in patients with incipient Raynaud's
      phenomenon. Whether laboratory markers that reflect a chronic inflammatory
      process are directly related to mortality in Raynaud's phenomenon is not known.
      METHODS: In total, 2958 patients with incipient Raynaud's phenomenon without
      previously known connective tissue disease (CTD) were enrolled. At their initial
      presentation, laboratory tests for C-reactive protein (CRP), leucocytes,
      fibrinogen and the haemoglobin concentration were obtained. In addition, nailfold
      capillaries and antinuclear antibodies (ANA) were assessed. Patients' mortality
      was recorded through a median follow-up period of 9.3 years. RESULTS: Baseline
      CRP, fibrinogen and haemoglobin concentration were associated with long-term
      mortality in an individual analysis of patients with incipient Raynaud's
      phenomenon. In a multivariable model including patients' age, nailfold
      capillaries and ANA, a low haemoglobin concentration remained independently
      related to future mortality. Amongst potential predictors for mortality in
      patients with Raynaud's phenomenon, a low haemoglobin concentration was most
      strongly related to patients' mortality risk. CONCLUSION: In Raynaud's
      phenomenon, laboratory markers that can be attributed to a chronic inflammatory
      state independently yield prognostic information in addition to the presence of
      abnormal nailfold capillaries and ANA. Amongst all prognostic markers, the
      haemoglobin concentration is most strongly related to patients' mortality in
      Raynaud's phenomenon.

PMID- 29068147
TI  - R-based Tool for a Pairwise Structure-activity Relationship Analysis.
AB  - The Structure-Activity Relationship analysis is a complex process that can be
      enhanced by computational techniques. This article describes a simple tool for
      SAR analysis that has a graphic user interface and a flexible approach towards
      the input of molecular data. The application allows calculating molecular
      similarity represented by Tanimoto index & Euclid distance, as well as,
      determining activity cliffs by means of Structure-Activity Landscape Index. The
      calculation is performed in a pairwise manner either for the reference compound
      and other compounds or for all possible pairs in the data set. The results of SAR
      analysis are visualized using two types of plot. The application capability is
      demonstrated by the analysis of a set of COX2 inhibitors with respect to
      Isoxicam. This tool is available online: it includes manual and input file
      examples.

PMID- 29068148
TI  - Impact of obesity on annual medical expenditures and diabetes care in Japanese
      patients with type 2 diabetes mellitus.
AB  - AIMS/INTRODUCTION: Diabetes and obesity are important health and economic
      concerns. We investigated the influence of obesity on diabetes control, the
      annual medical expenditures and medications in Japanese patients with type 2
      diabetes who were relatively lean in comparison with those in Western countries.
      MATERIALS AND METHODS: A total of 402 Japanese patients with type 2 diabetes were
      enrolled and their annual medical expenditures investigated. Obesity was defined
      as body mass index >=25 kg/m2 , according to the obesity classifications from the
      Japan Society for the Study of Obesity. RESULTS: A total of 165 patients (41.0%)
      were classified as obese. The obese group was younger, had poor glycemic control
      and higher frequency of hypertension than the non-obese group. The median total
      annual medical expenditures for all participants was Y269,333 (interquartile
      range Y169,664-437,437), which was equivalent to approximately $US2,450. The
      annual medical expenditure was significantly higher in patients with obesity than
      in non-obese patients (P < 0.001). This difference was mainly attributed to the
      annual expenditures for medication and hospitalization. In particular, the
      medication expenditures and the average number of drug classes for hyperglycemia
      and hypertension were significantly higher in the obese group. CONCLUSIONS:
      Japanese patients with type 2 diabetes and obesity had higher annual medical
      expenditures and a larger number of medications, but their diabetes control care
      was insufficient in comparison with those without obesity. Further studies are
      required to assess the effect of reducing bodyweight on diabetes control and
      costs.

PMID- 29068149
TI  - One-step Preparation of Carbon-based Solid Acid Catalyst from Water Hyacinth
      Leaves for Esterification of Oleic Acid and Dehydration of Xylose.
AB  - Carbon-based solid acid catalysts were successfully obtained via one-step
      hydrothermal carbonization (HTC) of water hyacinth (WH) in the presence of p
      toluenesulfonic acid (PTSA). Increasing the HTC temperature from 180 to 240 
      degrees C resulted in carbonaceous materials with increased sulfur content and
      less adsorbed water. The material obtained at 220  degrees C (WH-PTSA-220)
      contains the highest amount of acid sites and promotes the highest initial rate
      of two transformations, that is, methanolysis of oleic acid and dehydration of
      xylose to furfural. While all PSTA-treated WH catalysts gave comparable fatty
      acid conversions (~97 %) and furfural yields (~60 %) after prolonged reaction
      times, the WH-PTSA-240 system bearing a relatively low acid density maintains the
      most favorable reusability profile. Higher HTC temperatures (220-240  degrees C)
      improved the catalyst reusability profiles due to graphitization and
      hydrophobicity of the carbon surface. The catalyst systems derived herein from
      biomass may have potential applications in biorefining platforms, utilizing the
      conversion of waste biomass to chemicals.

PMID- 29068151
TI  - Cytomegalovirus retinitis in HIV-negative patients - associated conditions,
      clinical presentation, diagnostic methods and treatment strategy.
AB  - In recent years, numerous reports have tied cytomegalovirus retinitis (CMVR) with
      multiple systemic conditions in the absence of human immunodeficiency virus (HIV)
      or acquired immunodeficiency syndrome (AIDS). These range from reports in
      apparently healthy individuals, through conditions rendering limited immune
      dysfunction such as advanced age and diabetes mellitus, and finally severe immune
      dysfunction such as in haematological and rheumatological conditions. Reports are
      also emerging, suggesting that induced local ocular immunosuppression is a risk
      factor for CMVR. We herein present a comprehensive collection of the accumulated
      findings regarding CMVR in non-HIV patients. We summarize the spectrum of
      underlying morbidity that has been associated with CMVR, its clinical
      presentation, diagnostic methods and treatment choice in the attempt to suggest
      the optimal treatment strategy in this complicated and diverse patient population
      which is still currently lacking a consensus.

PMID- 29068150
TI  - Detection of circulating tumor cells using oHSV1-hTERT-GFP in lung cancer.
AB  - BACKGROUND: This study was conducted to evaluate the clinical utility of the
      oHSV1-hTERT-GFP circulating tumor cell (CTC) detection method in the peripheral
      blood of patients with lung cancer by comparing its sensitivity to the CellSearch
      CTC detection method. METHODS: The oHSV1-hTERT-GFP and CellSearch CTC detection
      methods were compared using peripheral blood samples of patients pathologically
      diagnosed with lung cancer. RESULTS: A total of 240 patients with lung cancer
      were recruited, including 89 patients who were newly diagnosed and 151 patients
      who had previously received treatment. Sixty-six newly diagnosed patients were
      evaluated using both methods. The CTC detection rates were 71.2% and 33.3% using
      the oHSV1-hTERT-GFP and CellSearch methods, respectively; this difference was
      statistically significant (P = 0.000). Among the entire cohort (n = 240), the CTC
      detection rate using the oHSV1-hTERT-GFP method was 76.3%, with a CTC count of 0
      81. The CTC detection rates were 76.7%, 68.9%, and 76.3% in patients with
      squamous cell carcinoma, adenocarcinoma, and small cell lung cancer,
      respectively. There was no statistically significant difference in the CTC
      detection rates between these different pathological subtypes (P = 0.738). The
      CTC detection rates of 79.8% and 74.4% in patients with stage I-III and IV lung
      cancer, respectively, were not significantly different (P = 0.427). CONCLUSION:
      The oHSV1-hTERT-GFP method is highly effective for detecting CTCs in patients
      with lung cancer, independent of pathological type and disease stage, and is
      ideal for large-scale clinical applications.

PMID- 29068152
TI  - Review and experimental evaluation of the embryonic development and evolutionary
      history of flipper development and hyperphalangy in dolphins (Cetacea: Mammalia).
AB  - Cetaceans are the only mammals to have evolved hyperphalangy, an increase in the
      number of phalanges beyond the mammalian plesiomorphic condition of three
      phalanges per digit. In this study, cetaceans were used as a novel model to
      review previous studies of mammalian hyperphalangy and contribute new
      experimental evidence as to the molecular origins of this phenotype in embryos of
      the pantropical spotted dolphin (Stenella attenuata). Results show embryos of
      dolphins, mice, and pigs share similar spatiotemporal patterns of signaling
      proteins known to shape limbs of mammals (e.g., FGF8, BMP2/4, WNT, GREM).
      However, fetal dolphins differ in that their interdigital tissues are retained,
      instead of undergoing apoptosis, and that multiple waves of interdigital signals
      likely contribute to the patterning of supernumerary joints and phalanges in
      adjacent digits. Integration of fossil and experimental evidence suggests that
      the presence of interdigital webbing within the fossils of semi-aquatic
      cetaceans, recovered from the Eocene Epoch (49Ma), was probably the result of BMP
      antagonists counteracting interdigital apoptosis during embryonic limb
      development. Modifications to signals originating in these interdigital tissues
      likely contributed to the origin of an incipient form of hyperphalangy in
      obligatorily aquatic cetaceans about 35Ma. Finally, an extreme form of
      hyperphalangy, with six or more phalanges per digit, evolved independently in
      rorqual whales (Balaenopteridae) and delphinids, and was probably associated with
      a wave of signaling within the interdigital tissues.

PMID- 29068153
TI  - Reduction of groin wound complications in vascular surgery patients using closed
      incision negative pressure therapy (ciNPT): a prospective, randomised, single
      institution study.
AB  - Groin wound infections in patients undergoing vascular procedures often cause a
      lengthy process of wound healing. Several clinical studies and case reports show
      a reduction of surgical site infections (SSIs) in various wound types after using
      closed incision negative pressure therapy (ciNPT). The aim of this prospective,
      randomised, single-institution study was to investigate the effectiveness of
      ciNPT (PREVENATM Therapy) compared to conventional therapy on groin incisions
      after vascular surgery. From 1 February to 30 October 2015, 100 patients with 129
      groin incisions were analysed. Patients were randomised and treated with either
      ciNPT (n = 58 groins) or the control dressing (n = 71 groins). ciNPT was applied
      intraoperatively and removed on days 5-7 postoperatively. The control group
      received a conventional adhesive plaster. Wound evaluation based on the Szilagyi
      classification took place postoperatively on days 5-7 and 30. Compared to the
      control group, the ciNPT group showed a significant reduction in wound
      complications (P < 0.0005) after both wound evaluation periods and in revision
      surgeries (P = 0.022) until 30 days postoperatively. Subgroup analysis revealed
      that ciNPT had a significant effect on almost all examined risk factors for wound
      healing. ciNPT significantly reduced the incidence of incision complications and
      revision procedures after vascular surgery.

PMID- 29068154
TI  - Liquid Hydrocarbon Production from CO2 : Recent Development in Metal-Based
      Electrocatalysis.
AB  - Rising levels of CO2 accumulation in the atmosphere have attracted considerable
      interest in technologies capable of CO2 capture, storage and conversion. The
      electrochemical reduction of CO2 into high-value liquid organic products could be
      of vital importance to mitigate this issue. The conversion of CO2 into liquid
      fuels by using photovoltaic cells, which can readily be integrated in the current
      infrastructure, will help realize the creation of a sustainable cycle of carbon
      based fuel that will promote zero net CO2 emissions. Despite promising findings,
      significant challenges still persist that must be circumvented to make the
      technology profitable for large-scale utilization. With such possibilities, this
      Minireview presents the current high-performing catalysts for the electrochemical
      reduction of CO2 to liquid hydrocarbons, address the limitations and unify the
      current understanding of the different reaction mechanisms. The Minireview also
      explores current research directions to improve process efficiencies and
      production rate and discusses the scope of using photo-assisted electrochemical
      reduction systems to find stable, highly efficient catalysts that can harvest
      solar energy directly to convert CO2 into liquid hydrocarbons.

PMID- 29068157
TI  - Running INTERFERONce on immunotherapy.

PMID- 29068155
TI  - Longitudinal assessment of T cell inhibitory receptors in liver transplant
      recipients and their association with posttransplant infections.
AB  - Current immunosuppression regimens in organ transplantation primarily inhibit T
      cells. However, T cells are also critical in protective immunity, especially in
      immune-compromised patients. In this study, we examined the association of T cell
      dysfunction, as marked by expression of T cell exhaustion molecules, and
      posttransplant infections in a cohort of liver transplant patients. We focused on
      Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3),
      which are potent co-inhibitory receptors, and their persistent expression often
      leads to T cell dysfunction and compromised protective immunity. We found that
      patients with the highest expression of PD-1 +Tim-3+ T cells in the memory
      compartment before transplantation had increased incidence of infections after
      liver transplantation, especially within the first 90 days. Longitudinal analysis
      in the first year showed a strong association between variability of PD-1 and Tim
      3 expression by T cells and infectious episodes in transplant patients.
      Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced
      capacity in producing interferon (IFN)-gamma in vitro, and this reduced IFN-gamma
      production could be partially reversed by blocking PD-1 and Tim-3. Interestingly,
      the percentage of Foxp3+ regulatory T cells in liver transplant patients was
      stable in the study period. We concluded that the functional status of T cells
      before and after liver transplantation, as shown by PD-1 and Tim-3 expression,
      may be valuable in prognosis and management of posttransplant infections.

PMID- 29068156
TI  - Ruthenium Water Oxidation Catalysts based on Pentapyridyl Ligands.
AB  - Ruthenium complexes containing the pentapyridyl ligand 6,6''-(methoxy(pyridin-2
      yl)methylene)di-2,2'-bipyridine (L-OMe) of general formula trans-[RuII (X)(L-OMe
      kappa-N5 )]n+ (X=Cl, n=1, trans-1+ ; X=H2 O, n=2, trans-22+ ) have been isolated
      and characterized in solution (by NMR and UV/Vis spectroscopy) and in the solid
      state by XRD. Both complexes undergo a series of substitution reactions at
      oxidation state RuII and RuIII when dissolved in aqueous triflic acid
      trifluoroethanol solutions as monitored by UV/Vis spectroscopy, and the
      corresponding rate constants were determined. In particular, aqueous solutions of
      the RuIII -Cl complex trans-[RuIII (Cl)(L-OMe-kappa-N5 )]2+ (trans-12+ )
      generates a family of Ru aquo complexes, namely trans-[RuIII (H2 O)(L-OMe-kappa
      N5 )]3+ (trans-23+ ), [RuIII (H2 O)2 (L-OMe-kappa-N4 )]3+ (trans-33+ ), and
      [RuIII (Cl)(H2 O)(L-OMe-kappa-N4 )]2+ (trans-42+ ). Although complex trans-42+ is
      a powerful water oxidation catalyst, complex trans-23+ has only a moderate
      activity and trans-33+ shows no activity. A parallel study with related complexes
      containing the methyl-substituted ligand 6,6''-(1-pyridin-2-yl)ethane-1,1-diyl)di
      2,2'-bipyridine (L-Me) was carried out. The behavior of all of these catalysts
      has been rationalized based on substitution kinetics, oxygen evolution kinetics,
      electrochemical properties, and density functional theory calculations. The best
      catalyst, trans-42+ , reaches turnover frequencies of 0.71 s-1 using CeIV as a
      sacrificial oxidant, with oxidative efficiencies above 95 %.

PMID- 29068158
TI  - Development of an Adult Physiologically Based Pharmacokinetic Model of
      Solithromycin in Plasma and Epithelial Lining Fluid.
AB  - Solithromycin is a fluoroketolide antibiotic under investigation for community
      acquired bacterial pneumonia (CABP). We developed a whole-body physiologically
      based pharmacokinetic (PBPK) model for solithromycin in adults using PK-Sim and
      MoBi version 6.2, which incorporated time-dependent CYP3A4 auto-inhibition. The
      model was developed and evaluated using plasma and epithelial lining fluid (ELF)
      concentration data from 100 healthy subjects and 22 patients with CABP (1,966
      plasma, 30 ELF samples). We performed population simulations and calculated the
      number of observations falling outside the 90% prediction interval. For the oral
      regimen (800 mg on day 1 and 400 mg daily on days 2-5) that was evaluated in
      phase III studies, 11% and 23% of observations from healthy adults fell outside
      the 90% prediction interval for plasma and ELF, respectively. This regimen should
      be effective because >=97% of simulated adults achieved area under the
      concentration vs. time curve (AUC) to minimum inhibitory concentration ratios
      associated with a log10 colony forming unit reduction in ELF.

PMID- 29068159
TI  - Sputum TWEAK expression correlates with severity and degree of control in non
      eosinophilic childhood asthma.
AB  - BACKGROUND: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known
      to play a role in the pathogenesis of various inflammatory diseases. However, no
      study has been performed on childhood asthma. METHODS: Ninety-five children with
      asthma and 78 controls aged 5-18 years were included. Sputum induction, pulmonary
      function test (PFT), and methacholine challenge test were performed. The subjects
      were divided into the eosinophilic airway (EA) and non-EA (NEA) groups based on
      sputum analysis and into the high and low TWEAK groups according to the TWEAK
      cutoff level (263.0 pg/mL). TWEAK in induced sputum supernatant was measured
      through enzyme-linked immunosorbent assay. RESULTS: Children with asthma had
      higher TWEAK levels than healthy controls (493.0 [157.1-904.3] vs 118.2 (67.5
      345.5) pg/mL, P < .001). Sputum TWEAK levels were significantly correlated with
      PFT parameters reflecting airway obstruction. This association was particularly
      prominent in subjects with NEA inflammation. Significant differences in FEF25-75
      (maximum mid-expiratory flow, % predicted; P = .017), AX (reactance area; P <
      .001), R5-R20 (difference between resistance at 5 and 20 Hz; P = .025), and X5
      (reactance at 5 Hz, % predicted; P < .001) were noted between the high and low
      TWEAK groups within the NEA group. Sputum TWEAK level also showed significant
      positive correlations with asthma severity (r = .358, P = .001) and control
      status (r = .470, P < .001), distinctively in subjects with NEA inflammation.
      CONCLUSIONS: Airway TWEAK may play a role in small airway inflammation especially
      in children with non-eosinophilic asthma.

PMID- 29068160
TI  - The effect of fluoride on the structure, function, and proteome of intestinal
      epithelia.
AB  - Fluoride exposure is widespread, with drinking water commonly containing natural
      and artificially added sources of the ion. Ingested fluoride undergoes absorption
      across the gastric and intestinal epithelia. Previous studies have reported
      adverse gastrointestinal effects with high levels of fluoride exposure. Here, we
      examined the effects of fluoride on the transepithelial ion transport and
      resistance of three intestinal epithelia. We used the Caco-2 cell line as a model
      of human intestinal epithelium, and rat and mouse colonic epithelia for purposes
      of comparison. Fluoride caused a concentration-dependent decline in forskolin
      induced Cl- secretion and transepithelial resistance of Caco-2 cell monolayers,
      with an IC50 for fluoride of about 3 mM for both parameters. In the presence of 5
      mM fluoride, transepithelial resistance fell exponentially with time, with a t1/2
      of about 7 hours. Subsequent imaging by immunofluorescence and scanning electron
      microscopy showed structural abnormalities in Caco-2 cell monolayers exposed to
      fluoride. The Young's modulus of the epithelium was not affected by fluoride,
      although proteomic analysis revealed changes in expression of a number of
      proteins, particularly those involved in cell-cell adhesion. In line with its
      effects on Caco-2 cell monolayers, fluoride, at 5 mM, also had profound effects
      on Cl- secretion and transepithelial resistance of both rat and mouse colonic
      epithelia. Our results show that treatment with fluoride has major effects on the
      structure, function, and proteome of intestinal epithelia, but only at
      concentrations considerably higher than those likely to be encountered in vivo,
      when much lower fluoride doses are normally ingested on a chronic basis.

PMID- 29068162
TI  - A method for predicting peak work rate for cycle ergometer and treadmill ramp
      tests.
AB  - BACKGROUND: Prediction of peak work rate (WRpeak) for incremental exercise
      testing (IET) is important to bring subjects to their maximal performance within
      the recommended 8-12 min. This study developed a novel method for prediction of
      WRpeak for IET on cycles and treadmills. METHODS: Peak metabolic equivalent of
      task (METpred) was predicted based on an existing non-exercise prediction
      formula, and then, predicted peak work rate (WRpred) was derived from separate
      formulae for the cycle and the treadmill. Eighteen healthy subjects were
      included. RESULTS: In males, there was no difference between WRpred versus WRpeak
      for both the cycle ergometer (277.7 versus 275.6 W, P = 0.70) and the treadmill
      (264.1 versus 260.5, P = 0.58). In females, there was no difference between
      WRpred versus WRpeak for the cycle ergometer (187.1 versus 188.3 W, P = 0.90),
      but a significant difference was found between WRpred versus WRpeak on the
      treadmill (178.6 versus 151.9 W, P<0.05). For males, the mean absolute percentage
      errors for WRpred versus WRpeak were 4.6% and 5.7% for the cycle and treadmill,
      respectively. For females, the errors were 12.2% and 20.8%. The algorithm was
      successful in achieving the required duration of 8-12 min in 33 of 36 cases.
      CONCLUSIONS: The peak work rate prediction protocol was accurate in male subjects
      for both the cycle and the treadmill. In female subjects, the method was accurate
      for the cycle, but systematically overpredicted the peak work rate on the
      treadmill. The protocol requires further adaptation for females on the treadmill.

PMID- 29068163
TI  - Bioprosthetic tricuspid valve thrombosis: Percutaneous PFO closure to improve
      hypoxia and respiratory failure.
AB  - Prosthetic valve thrombosis (PVT) is an increasingly recognized complication of
      bioprosthetic valve replacement, often resulting in abnormal hemodynamic,
      endothelial, and hemostatic conditions. Bioprosthetic PVT may lead to significant
      hemodynamic and clinical effects. In hemodynamically stable patients, first-line
      treatment for bioprosthetic PVT is systemic anticoagulation. However, concomitant
      cardiovascular pathology may lead to additional clinical sequalae that requires
      acute therapeutic interventions. We describe two cases in which bioprosthetic PVT
      leads to hemodynamically significant intracardiac shunting through pre-existing
      patent foramen ovales requiring percutaneous closure with a Cribriform AMPLATZER
      occluder device. We also review the treatment for bioprosthetic PVT and discuss
      important clinical and hemodynamic considerations.

PMID- 29068164
TI  - Predictors of in-hospital effectiveness and complications of rotational
      atherectomy (from the ORPKI Polish National Registry 2014-2016).
AB  - OBJECTIVE: The aim of the study was to assess trends in the use and
      periprocedural outcomes of rotational atherectomy (RA) in Poland between January
      2014 and December 2016. BACKGROUND: In recent years, due to the aging population,
      RA is becoming more commonly used to treat heavily calcified coronary artery
      stenoses. METHODS: Data were prospectively collected using the Polish
      Cardiovascular Intervention Society national registry on all percutaneous
      coronary intervention (PCI) procedures performed in Poland. In total, 1,175 RA
      procedures were recorded from 317,175 PCI procedures (incidence of 0.37%).
      RESULTS: Patients undergoing RA were older (71.7 +/- 9.7 vs. 66.9 +/- 10.8, P <
      0.00001) and less often males (68.3% vs. 76.4%, P < 0.00001). The complication
      rate was significantly higher in the RA group (P = 0.0012) with the leading
      coronary artery perforation (CAP) (P < 0.0001). Complication frequency decreased
      significantly in the last 3 years and was accompanied by an increase in the
      percentage of radial access and patients with stable angina. Among several
      predictors of the use of RA during PCI in multivariate analysis, the strongest
      one was previous coronary artery by-pass grafting (P < 0.0001), whereas the
      strongest, predictor of CAP was the RA procedure (P = 0.00004). The increase in
      RA frequency over the last 3 years may reflect population aging, some
      fluctuations in indications for RA and reimbursement policies. CONCLUSIONS: We
      observed a substantial increase in the utilization of RA during PCIs performed in
      Poland; however, it still needs to be increased. Decreased frequency of RA
      procedures follows change in indications for RA and vascular access.
      Periprocedural complication rates significantly decreased over the last 3 years.

PMID- 29068165
TI  - Identification of chlamydial T3SS inhibitors through virtual screening against
      T3SS ATPase.
AB  - Chlamydia trachomatis is a widespread sexually transmitted pathogen that resides
      within a special vacuole inside host cells. Although acute infection can be
      treated with antibiotics, chlamydia can enter persistent state, leading to
      chronic infection that is difficult to cure. Thus, novel anti-chlamydial
      compounds active against persistent chlamydia are required. Chlamydiae rely upon
      type III secretion system (T3SS) to inject effector proteins into host cell
      cytoplasm, and T3SS inhibitors are viewed as promising compounds for treatment of
      chlamydial infections. C. trachomatis ATPase SctN is an important T3SS component
      and has not been targeted before. We thus used virtual screening against homology
      modeled SctN structure to search for SctN inhibitors. Selected compounds were
      tested for their ability to inhibit chlamydial survival and development within
      eukaryotic cells, and for the ability to suppress normal T3SS functioning. We
      identified two compounds that were able to block normal protein translocation
      through T3SS and inhibit chlamydial survival within eukaryotic cells in 50-100
      MUm concentrations. These two novel T3SS inhibitors also possessed relatively low
      toxicity toward eukaryotic cells. A small series of derivatives was further
      synthesized for the most active of two inhibitors to probe SAR properties.

PMID- 29068166
TI  - Meta-analysis of transfemoral TAVR versus surgical aortic valve replacement.
AB  - BACKGROUND: In the recently concluded PARTNER 2 trial, TF-TAVR cohort was shown
      to have lower risks of death or disabling strokes as compared to SAVR, whereas
      the outcomes with transthoracic TAVR were comparable with SAVR. METHODS: We
      searched PubMed, EMBASE, Web of Science, and Google Scholar for all comparison
      studies between TAVR and SAVR and mortality as an outcome, irrespective of
      surgical risk. Randomized controlled trials and propensity-score-matched cohort
      studies that used a transfemoral approach exclusively or stratified results by
      route of access and reported data for TF-TAVR patients were eligible for
      inclusion. Outcomes of interest included 30-day and 1-year mortality, and 30-day
      complications. If significant heterogeneity was found in the random effects meta
      analyses, a sensitivity analysis which individually removed each study was
      conducted. RESULTS: Seven studies reported results on TF-TAVR. Compared with
      SAVR, TF-TAVR had comparable 30-day mortality (RR 0.79, 95% CI 0.58, 1.06), 1
      year mortality (RR 0.91, 95% CI 0.78, 1.08) and 30-day risk of bleeding (RR 0.70,
      95% CI 0.31, 1.57). However, TF-TAVR was associated with lower 30-day risks of
      atrial fibrillation (RR 0.28, 95% CI 0.17, 0.45), acute kidney injury (RR 0.38,
      95% CI 0.20, 0.71), and myocardial infarction (RR 0.41, 95% CI 0.23, 0.75) at a
      cost of higher incidences of vascular complications (RR 6.10, 95% CI 2.92, 12.73)
      and pacemaker implantations (RR 3.29, 95% CI 1.41, 7.65). CONCLUSIONS: TF-TAVR is
      associated with lower 30-day risks of myocardial infarction compared to SAVR.
      Further studies are required to investigate the role of myocardial injury on
      overall TF-TAVR outcomes.

PMID- 29068167
TI  - Introduction to Volume 9, Issue 4 of topiCS.

PMID- 29068169
TI  - Editors' Introduction: Sketching and Cognition.

PMID- 29068170
TI  - Antidote Availability in Saudi Arabia Hospitals in the Riyadh Province.
AB  - Inadequate antidote stocking is a global problem in hospitals. Insufficient
      supplies and delays in the administration of antidotes could lead to death and
      additional potentially negative clinical consequences. Our objective was to
      determine the availability of antidotes in hospitals listed on the Saudi Ministry
      of Health website in the Riyadh Province and to evaluate the leading poison in
      Saudi Arabia. A cross-sectional study was conducted using questionnaires. The
      questionnaires were distributed to pharmacist directors and emergency room
      treating physicians in 17 public hospitals throughout the Riyadh Province. None
      (0/17) of the pharmacies contained the 24 recommended essential antidotes by the
      expert consensus guidelines for stocking of antidotes in hospitals. Polyvalent
      scorpion antivenom, atropine sulphate, calcium gluconate, flumazenil and naloxone
      hydrochloride were stocked in 94.12% (16/17) of hospitals. 66.67% of patients
      presented with osmolality, and 55.56% of referral patients with opiates,
      barbiturates, acetaminophen and salicylate. Our findings have important
      implications for healthcare institutions and pharmaceutical practices. National
      practice guidelines are needed to assist pharmacists in selecting appropriate
      antidotes based on the local pattern of poisoning incidents. Therefore, further
      study in the Kingdom of Saudi Arabia needs to be completed to fully evaluate the
      availability of antidotes throughout the country.

PMID- 29068161
TI  - DCC mutation update: Congenital mirror movements, isolated agenesis of the corpus
      callosum, and developmental split brain syndrome.
AB  - The deleted in colorectal cancer (DCC) gene encodes the netrin-1 (NTN1) receptor
      DCC, a transmembrane protein required for the guidance of commissural axons.
      Germline DCC mutations disrupt the development of predominantly commissural
      tracts in the central nervous system (CNS) and cause a spectrum of neurological
      disorders. Monoallelic, missense, and predicted loss-of-function DCC mutations
      cause congenital mirror movements, isolated agenesis of the corpus callosum
      (ACC), or both. Biallelic, predicted loss-of-function DCC mutations cause
      developmental split brain syndrome (DSBS). Although the underlying molecular
      mechanisms leading to disease remain poorly understood, they are thought to stem
      from reduced or perturbed NTN1 signaling. Here, we review the 26 reported DCC
      mutations associated with abnormal CNS development in humans, including 14
      missense and 12 predicted loss-of-function mutations, and discuss their
      associated clinical characteristics and diagnostic features. We provide an update
      on the observed genotype-phenotype relationships of congenital mirror movements,
      isolated ACC and DSBS, and correlate this to our current understanding of the
      biological function of DCC in the development of the CNS. All mutations and their
      associated phenotypes were deposited into a locus-specific LOVD
      (https://databases.lovd.nl/shared/genes/DCC).

PMID- 29068171
TI  - One-year clinical and computed tomography follow-up after implantation of
      bioresorbable vascular scaffolds in patients with coronary chronic total
      occlusions.
AB  - OBJECTIVES: To assess the safety and efficacy of everolimus-eluting bioresorbable
      scaffolds (BRS) in the treatment of chronic total occlusions (CTO) using
      noninvasive multislice computed tomography (MSCT) angiography at one-year follow
      up. BACKGROUND: Current evidence regarding the safety and efficacy of BRS for the
      percutaneous treatment of CTO is limited. METHODS: Between September 2013 and
      January 2016, patients who received one or more ABSORB BRSs were included at
      three centers. MSCT (including quantitative analysis) and clinical follow-up were
      performed at one year. RESULTS: Forty-one CTO patients were included. Mean age
      was 60 +/- 11 years and the majority was male (83%). Average Japanese CTO (J-CTO)
      score was 0.9 +/- 0.9. Seventy-one BRS were implanted in total with, on average,
      1.7 +/- 0.8 scaffolds/patient, and a total length of 43 +/- 20 mm and diameter of
      3.1 +/- 0.4 mm. One noncardiac death took place. MSCT angiography was performed
      in 34 (83%) patients: all scaffolds were patent, except in one patient, in whom a
      patent target vessel was present on subsequent diagnostic angiography. MSCT
      quality was sufficient for quantitative analyses in 27 patients (46 scaffolds):
      median reference versus scaffold minimal lumen diameter and minimal lumen area
      were measured, and showed a small difference of 0.1 mm (-0.2-0.4) (lumen diameter
      stenosis = 3.0%) and 0.5 mm2 (-1.0-2.0) (lumen area stenosis = 4.2%).
      CONCLUSIONS: The low number of events and high patency rate at 1 year are
      encouraging the further use of the ABSORB scaffold for CTOs with low J-CTO score.
      Noninvasive MSCT angiography is a valid tool to assess scaffold patency, although
      its image resolution limits the use for quantitative measurements.

PMID- 29068172
TI  - Increased frequency of retinopathy of prematurity over the last decade and
      significant regional differences.
AB  - PURPOSE: Retinopathy of prematurity (ROP) causes childhood blindness globally in
      prematurely born infants. Although increased levels of oxygen supply lead to
      increased survival and reduced frequency of cerebral palsy, increased incidence
      of ROP is reported. METHODS: With the help of a Swedish register for ROP,
      SWEDROP, national and regional incidences of ROP and frequencies of treatment
      were evaluated from 2008 to 2015 (n = 5734), as well as before and after targets
      of provided oxygen changed from 85-89% to 91-95% in 2014. RESULTS: Retinopathy of
      prematurity (ROP) was found in 31.9% (1829/5734) of all infants with a
      gestational age (GA) of <31 weeks at birth and 5.7% of the infants (329/5734) had
      been treated for ROP. Analyses of the national data revealed an increased
      incidence of ROP during the 8-year study period (p = 0.003), but there was no
      significant increase in the frequency of treatment. There were significant
      differences between the seven health regions of Sweden, regarding both incidence
      of ROP and frequency of treatment (p < 0.001). Comparison of regional data before
      and after the new oxygen targets revealed a significant increase in treated ROP
      in one region [OR: 2.24 (CI: 1.11-4.49), p = 0.024] and a borderline increase in
      one other [OR: 3.08 (CI: 0.99-9.60), p = 0.052]. CONCLUSION: The Swedish national
      ROP register revealed an increased incidence of ROP during an 8-year period and
      significant regional differences regarding the incidence of ROP and frequency of
      treatment.

PMID- 29068174
TI  - Comments on the association between reduced arterial stiffness and preserved
      diastolic function of the left ventricle in middle-aged and elderly patients.

PMID- 29068175
TI  - Micro-instillation of fluorescein with an inoculation loop for ocular surface
      staining in dry eye syndrome.
AB  - PURPOSE: To describe and validate the micro-instillation of fluorescein on the
      ocular surface by a disposable calibrated inoculation loop to improve corneal and
      conjunctival staining quality. METHODS: Accuracy and precision of the volume of
      0.5% sodium fluorescein collected by a single use 1 MUl-calibrated inoculation
      loop were measured using a precision balance. Twenty patients (40 eyes) suffering
      from dry eye syndrome were enrolled in a prospective interventional nonrandomized
      study. Fluorescein was instilled with the loop, and slit-lamp images were taken
      within 30 seconds using cobalt blue light with and without a yellow barrier
      filter. For comparison, after a washout period, the same images were retaken
      after instillation of one drop of fluorescein from a single-dose unit. The main
      outcome measure was the staining quality assessed by three experts, blind to the
      instillation method. Patient discomfort (tolerance, by a questionnaire) was also
      compared. RESULTS: The mean volume collected by the loop was 1.18 +/- 0.12 MUl,
      compared with 33.70 +/- 6.10 MUl using the single-dose unit. The loop avoided
      excess dye responsible for unpleasant tearing, masking of lesions and rapid
      diffusion into the stroma. Micro-instillation greatly improved image quality
      without losing information. The yellow filter further improved image contrast.
      Tolerance was excellent. CONCLUSION: The 1 MUl-calibrated inoculation loop is a
      safe, convenient, inexpensive, disposable, sterile, well-tolerated tool for
      reproducible micro-instillation of commercial fluorescein. By greatly improving
      staining quality, it will help standardize assessment of dry eye severity.

PMID- 29068177
TI  - Structural insights into anticancer activity of D-ring modified estrone
      derivatives using their lipophilicity in estimation of SAR and molecular docking
      studies.

PMID- 29068176
TI  - Factors associated with perceived donation-related financial burden among living
      kidney donors.
AB  - The perception of living kidney donation-related financial burden affects
      willingness to donate and the experience of donation, yet no existing tools
      identify donors who are at higher risk of perceived financial burden. We sought
      to identify characteristics that predicted higher risk of perceived financial
      burden. We surveyed 51 living kidney donors (LKDs) who donated from 01/2015 to
      3/2016 about socioeconomic characteristics, predonation cost concerns, and
      perceived financial burden. We tested associations between both self-reported and
      ZIP code-level characteristics and perceived burden using Fisher's exact test and
      bivariate modified Poisson regression. Donors who perceived donation-related
      financial burden were less likely to have an income above their ZIP code median
      (14% vs. 72%, P = .006); however, they were more likely than donors who did not
      perceive burden to rent their home (57% vs. 16%, P = .03), have an income <$60
      000 (86% vs. 20%, P = .002), or have had predonation cost concerns (43% vs. 7%, P
      = .03). Perceived financial burden was 3.6-fold as likely among those with
      predonation cost concerns and 10.6-fold as likely for those with incomes <$60
      000. Collecting socioeconomic characteristics and asking about donation-related
      cost concerns prior to donation might allow transplant centers to target
      financial support interventions toward potential donors at higher risk of
      perceiving donation-related financial burden.

PMID- 29068173
TI  - Mesenchymal Stem Cells: Potential Role in the Treatment of Osteochondral Lesions
      of the Ankle.
AB  - Given articular cartilage has a limited repair potential, untreated osteochondral
      lesions of the ankle can lead to debilitating symptoms and joint deterioration
      necessitating joint replacement. While a wide range of reparative and restorative
      surgical techniques have been developed to treat osteochondral lesions of the
      ankle, there is no consensus in the literature regarding which is the ideal
      treatment. Tissue engineering strategies, encompassing stem cells, somatic cells,
      biomaterials, and stimulatory signals (biological and mechanical), have a
      potentially valuable role in the treatment of osteochondral lesions. Mesenchymal
      stem cells (MSCs) are an attractive resource for regenerative medicine
      approaches, given their ability to self-renew and differentiate into multiple
      stromal cell types, including chondrocytes. Although MSCs have demonstrated
      significant promise in in vitro and in vivo preclinical studies, their success in
      treating osteochondral lesions of the ankle is inconsistent, necessitating
      further clinical trials to validate their application. This review highlights the
      role of MSCs in cartilage regeneration and how the application of biomaterials
      and stimulatory signals can enhance chondrogenesis. The current treatments for
      osteochondral lesions of the ankle using regenerative medicine strategies are
      reviewed to provide a clinical context. The challenges for cartilage
      regeneration, along with potential solutions and safety concerns are also
      discussed.

PMID- 29068178
TI  - ERRATA.

PMID- 29068179
TI  - ERRATA.

PMID- 29068180
TI  - Impact of Climate Change on Health From the Perspective of Catholic Relief
      Services.

PMID- 29068182
TI  - Obesity and reproduction: a study to determine how effectively medical education
      enhances awareness of the reproductive risks related to obesity.
AB  - OBJECTIVE: To explore awareness of the reproductive versus the medical risks of
      obesity in a medical and non-medical college educated population. METHODS: An
      exploratory prospective research design was used. A 26-question online survey was
      developed and offered to a sample of medical students/residents (n=325) and non
      medical college students (n=102). The data were analyzed using Graph Pad
      software. RESULTS: 102 non-medical undergraduate students (28% male and 72%
      female) and 325 resident physicians and medical students (46% male, 47% female,
      7% unspecified) responded. Both groups reported higher awareness of the general
      risks of obesity as compared to the reproductive risks. As expected, lay students
      reported less awareness of female reproductive issues as compared to the medical
      group (all p-values <0.01). Over 90% of respondents would be motivated to lose
      weight before pregnancy if they knew of these risks, with more than half planning
      to have children in the future. CONCLUSION: This exploratory study found that
      despite having at least a college education, the populations studied had
      relatively low levels of awareness of obesity-related reproductive risks. The
      medical population had much more knowledge about the other health risks of
      obesity. The survey provided initial data that might be used to consider
      knowledge gaps and strategies for engaging and educating medical trainees and the
      public about the reproductive risks of obesity.

PMID- 29068183
TI  - Assessing Changes to Medicaid Managed Care Regulations: Facilitating Integration
      of Physical and Behavioral Health Care.
AB  - Issue: As states consider how to effectively control Medicaid costs, many are
      looking to integrate behavioral and medical care, including long-term services
      and supports, particularly for individuals with complex needs. Goal: To summarize
      how recent federal regulations are encouraging an integrated approach to
      behavioral and physical health care. Findings and Conclusions: Two recent federal
      rules issued in 2016 are facilitating the transition to integrated care models:
      the Medicaid managed care rule and the Medicaid managed care mental health parity
      rule. These changes may not spell the end of fragmented systems, but they
      certainly do not support a status quo approach to care. While the regulations do
      not specifically address integrated care, they should facilitate and, in some
      instances, encourage, state movement to integrated care for Medicaid
      participants.

PMID- 29068181
TI  - Semen parameters in men with varicocele: DNA fragmentation, chromatin packaging,
      mitochondrial membrane potential, and apoptosis.
AB  - OBJECTIVE: To evaluate varicocele effects on conventional semen parameters: sperm
      DNA fragmentation, chromatin packaging, mitochondrial membrane potential (MMP)
      and sperm apoptosis. METHODS: A cross-sectional study was carried out with semen
      samples from 2,399 men of couples who attended an infertility clinic. A total of
      16.3% (391/2399) of the men were diagnosed with varicocele by a urologist.
      RESULTS: A regression analysis revealed that the percentages of sperm with DNA
      fragmentation, abnormal chromatin packaging, and abnormal MMP were significantly
      increased in individuals with varicocele, when compared to men without
      varicocele. Apoptosis was not influenced by varicocele. Conventional semen
      parameters were significantly worse in individuals with the disease. On the other
      hand, in men with varicocele, Spearman's correlation demonstrated that early
      apoptosis and abnormal MMP showed a positive and significant correlation with
      sperm DNA fragmentation. CONCLUSION: Men with varicocele had worse semen
      parameters, including increased levels of sperm DNA fragmentation, inactive
      mitochondria, and abnormal chromatin packaging. These changes are possible causes
      of infertility in individuals with varicocele.

PMID- 29068185
TI  - Do Conditional Cash Transfers Improve Child Health? Evidence from PROGRESA's
      Control Randomized Experiment.

PMID- 29068184
TI  - Medical Compliance and Income-Health Gradients.

PMID- 29068186
TI  - The Role of Information in Medical Markets: An Analysis of Publicly Reported
      Outcomes in Cardiac Surgery.

PMID- 29068187
TI  - Managed Care, Information, and Diffusion: The Case of Treatment for Heart-Attack
      Patients.

PMID- 29068188
TI  - Hospital Transaction Prices and Managed-Care Discounting for Selected Medical
      Technologies.

PMID- 29068189
TI  - The Productivity of Physician Specialization: Evidence from the Medicare Program.

PMID- 29068190
TI  - Identifying the Effects of the Americans with Disabilities Act Using State-Law
      Variation: Preliminary Evidence on Educational Participation Effects.

PMID- 29068191
TI  - Addiction and Cue-Triggered Decision Processes.
AB  - We propose a model of addiction based on three premises: (i) use among addicts is
      frequently a mistake; (ii) experience sensitizes an individual to environmental
      cues that trigger mistaken usage; (iii) addicts understand and manage their
      susceptibilities. We argue that these premises find support in evidence from
      psychology, neuroscience, and clinical practice. The model is tractable and
      generates a plausible mapping between behavior and the characteristics of the
      user, substance, and environment. It accounts for a number of important patterns
      associated with addiction, gives rise to a clear welfare standard, and has novel
      implications for policy.

PMID- 29068192
TI  - The Effect of Health Risk on Housing Values: Evidence from a Cancer Cluster.

PMID- 29068193
TI  - Biomimetic Inks Based on Cellulose Nanofibrils and Cross-Linkable Xylans for 3D
      Printing.
AB  - This paper presents a sustainable all-wood-based ink which can be used for 3D
      printing of constructs for a large variety of applications such as clothes,
      furniture, electronics, and health care products with a customized design and
      versatile gel properties. The 3D printing technologies where the material is
      dispensed in the form of liquids, so called inks, have proven suitable for 3D
      printing dispersions of cellulose nanofibrils (CNFs) because of their unique
      shear thinning properties. In this study, novel inks were developed with a
      biomimetic approach where the structural properties of cellulose and the cross
      linking function of hemicelluloses that are found in the plant cell wall were
      utilized. The CNF was mixed with xylan, a hemicellulose extracted from spruce, to
      introduce cross-linking properties which are essential for the final stability of
      the printed ink. For xylan to be cross-linkable, it was functionalized with
      tyramine at different degrees. Evaluation of different ink compositions by
      rheology measurements and 3D printing tests showed that the degree of tyramine
      substitution and the ratio of CNFs to xylan-tyramine in the prepared inks
      influenced the printability and cross-linking density. Both two-layered gridded
      structures and more complex 3D constructs were printed. Similarly to conventional
      composites, the interactions between the components and their miscibility are
      important for the stability of the printed and cross-linked ink. Thus, the
      influence of tyramine on the adsorption of xylan to cellulose was studied with a
      quartz crystal microbalance to verify that the functionalization had little
      influence on xylan's adsorption to cellulose. Utilizing xylan-tyramine in the CNF
      dispersions resulted in all-wood-based inks which after 3D printing can be cross
      linked to form freestanding gels while at the same time, the excellent printing
      properties of CNFs remain intact.

PMID- 29068194
TI  - Preparation of 3D Architecture Graphdiyne Nanosheets for High-Performance Sodium
      Ion Batteries and Capacitors.
AB  - Here, we apply three-dimensional (3D) architecture graphdiyne nanosheet (GDY-NS)
      as anode materials for sodium-ion storage devices achieving high energy and power
      performance along with excellent cyclic ability. The contribution of 3D
      architecture nanostructure and intramolecular pores of the GDY-NS can
      substantially optimize the sodium storage behavior through the accommodated
      intramolecular pore, 3D interconnective porous structure, and increased activity
      sites to facilitate a fast sodium-ion-diffusion channel. The contribution of
      butadiyne linkages and the formation of a stable solid electrolyte interface
      layer are directly confirmed through the in situ Raman measurement. The GDY-NS
      based sodium-ion batteries exhibit a stable reversible capacity of approximately
      812 mAh g-1 at a current density of 0.05 A g-1; they maintain more than 405 mAh g
      1 over 1000 cycles at a current density of 1 A g-1. Furthermore, the sodium-ion
      capacitors could deliver a capacitance more than 200 F g-1 over 3000 cycles at 1
      A g-1 and display an initial specific energy as high as 182.3 Wh kg-1 at a power
      density of 300 W kg-1 and maintain specific energy of 166 Wh kg-1 even at a power
      density of 15 000 W kg-1. The high energy and power density along with excellent
      cyclic performance based on the GDY-NS anode offers a great potential toward
      application on next-generation energy storage devices.

PMID- 29068195
TI  - Micro Galvanic Cell To Generate PtO and Extend the Triple-Phase Boundary during
      Self-Assembly of Pt/C and Nafion for Catalyst Layers of PEMFC.
AB  - The self-assembly powder (SAP) with varying Nafion content was synthesized and
      characterized by XRD, XPS, HRTEM, and mapping. It is observed that the oxygen
      from oxygen functional groups transfers to the surface of Pt and generate PtO
      during the process of self-assembly with the mechanism of micro galvanic cell,
      where Pt, carbon black, and Nafion act as the anode, cathode and electrolyte,
      respectively. The appearance of PtO on the surface of Pt leads to a turnover of
      Nafion structure, and therefore more hydrophilic sulfonic groups directly contact
      with Pt, and thus the triple-phase boundary (TPB) has been expanded.

PMID- 29068196
TI  - Time Release of Encapsulated Additives for Enhanced Performance of Lithium-Ion
      Batteries.
AB  - Time release of encapsulated vinylene carbonate (VC) from microcapsules in Li-ion
      batteries is demonstrated to enhance the rate performance without sacrificing
      capacity retention. VC-filled microcapsules are successfully prepared by the
      solvent exchange method that allows VC to diffuse through the microcapsule shell
      wall at an elevated temperature. The concentration of VC added directly to the
      electrolyte in a pouch cell (2 wt %) significantly decreases after the first
      cycle at C/10-rate. In pouch cells that contain 5 wt % VC-filled microcapsules,
      the concentration of VC increases from 0 to 3 wt % over the first cycle because
      of the diffusion of microencapsulated VC in the electrolyte. Electrochemical
      impedance spectroscopy, rate capability, and long-term cycling tests are
      conducted for pouch cells with VC additives (0, 2, and 5 wt %) and VC
      microcapsules (5 wt %). Pouch cells with both 5 wt % VC additive and
      microencapsulated VC show improved capacity retention over 400 cycles at 1 C-rate
      compared to the cells without VC additive. When VC is added directly, the high
      initial concentration leads to increased interfacial resistance and decreased
      rate capability. By contrast, time release of microencapsulated VC by diffusion
      through microcapsules increases the discharge capacity 2.5 times at 5 C-rate
      compared to the direct VC addition to the electrolyte.

PMID- 29068197
TI  - Identification of Lattice Oxygen in Few-Layer Black Phosphorous Exfoliated in
      Ultrahigh Vacuum and Largely Improved Ambipolar Field-Effect Mobilities by
      Hydrogenation and Phosphorization.
AB  - Black phosphorus (BP) has recently attracted considerable attention due to its
      unique structure and fascinating optical and electronic properties as well as
      possible applications in photothermal agents. However, its main drawback is rapid
      degradation in ambient environments of H2O and O2, which has led to much research
      on the improvement of its stability. Unfortunately, this research has not shown
      great improvement in carrier mobilities. Here, we perform scanning tunneling
      microscopy observations of few-layer BP (FLBP) sheets exfoliated in ultrahigh
      vacuum and reveal, for the first time, the existence of lattice oxygen introduced
      during crystal growth. As a proof-of-concept application, hydrogenation is
      conducted to remove the lattice oxygen atoms followed by phosphorization, which
      repairs the phosphorous vacancies caused by mechanical exfoliation and
      hydrogenation. The resulting FLBP sheets show high ambipolar field-effect
      mobilities of 1374 cm2 V-1 s-1 for holes and 607 cm2 V-1 s-1 for electrons at 2
      K. After storage in air for 3 days, the hole and electron mobilities only
      decrease to 1181 and 518 cm2 V-1 s-1, respectively, and no structural degradation
      is observed. This work suggests an effective means to improve both the mobility
      and stability of BP sheets rendering practical application of FLBP sheets
      possible.

PMID- 29068198
TI  - Perspectives for Upconverting Nanoparticles.
AB  - Upconverting nanoparticles (UCNPs) are inorganic crystalline nanomaterials that
      can convert near-infrared (NIR) excitation light into visible and ultraviolet
      emission light. Excitation with NIR light minimizes autofluorescence background
      and enables deeper penetration into biological samples due to reduced light
      scattering. Although these optical features make UCNPs promising candidates for
      bioanalytical and biomedical applications, the performance of UCNPs is
      compromised by their low optical brightness. Research in the field of UCNP
      technology focuses on strategies to boost upconversion luminescence brightness
      and efficiencies. In this Perspective, I discuss challenges associated with the
      use of UCNPs and provide a 10-year proposed strategic plan to enable translation
      of UCNP technology from the academic stage into real world products and
      applications.

PMID- 29068199
TI  - Understanding the Scarcity of Thorium Peroxide Clusters.
AB  - The reaction of Th(NO3)4.5H2O with 3 equiv of 2,2',6',2"-terpyridine (terpy) in a
      mixture of acetonitrile and methanol results in formation of the trinuclear
      thorium peroxide cluster [Th(O2)(terpy)(NO3)2]3. This cluster is assembled via
      bridging by MU-eta2:eta2 peroxide anions between thorium centers. It decomposes
      upon removal from the mother liquor to yield Th(terpy)(NO3)4 and
      Th(terpy)(NO3)4(EtOH). The peroxide formation appears to be radiolytic in origin
      and is, most likely, generated from radiolysis of water by short-lived daughters
      generated from 232Th decay. This cluster does not form when freshly
      recrystallized Th(NO3)4.5H2O is used as the starting material and requires an
      aged source of thorium. Analysis of the bonding in these clusters shows that,
      unlike uranium(VI) peroxide interactions, thorium(IV) complexation by peroxide is
      quite weak and largely ionic. This explains its much lower stability, which is
      more comparable to that observed in similar zirconium(IV) peroxide clusters.

PMID- 29068200
TI  - Modulating Slow Magnetic Relaxation of Dysprosium Compounds through the Position
      of Coordinating Nitrate Group.
AB  - A chain complex [Dy(L)(NO3)2CH3OH]n (1) and a dinuclear compound
      [Dy2(L)2(NO3)4(CH3OH)2].2CH3OH (2) were synthesized by the assembly of a novel
      pyridine-N-oxide-containing ligand with dysprosium nitrate under different
      reaction temperatures, where two coordinating nitrates are located in para or
      ortho position with respect to each other around dysprosium ions. Magnetic
      studies indicate that the chain complex with two para-coordinating nitrates shows
      fast quantum tunnelling of the magnetization under zero direct-current field,
      while the dinuclear complex with two ortho-coordinating nitrates exhibits a
      thermal-activated process with an effective energy barrier of 51 K. Theoretical
      and magneto-structural correlation studies indicate that position change of
      coordinating nitrates can significantly modulate the crystal field around
      dysprosium ion and further lead to their different relaxation behaviors.

PMID- 29068201
TI  - Lead-Free Hybrid Material with an Exceptional Dielectric Phase Transition Induced
      by a Chair-to-Boat Conformation Change of the Organic Cation.
AB  - Hybrid organic-inorganic perovskite materials have demonstrated great potential
      in the field of photovoltaics and photoelectronics. On the basis of the high
      degree of structural flexibility and compatibility, diverse molecular functional
      materials have been assembled by modifying the length of the organic components
      and/or dimensionality of the inorganic frameworks. In this paper, we present a
      chiral lead-free organic-inorganic hybrid, (piperidinium)2SbCl5 (1), which
      follows the one-dimensional inorganic frameworks of the corner-sharing SbCl6
      octahedra. Strikingly, 1 displays a dielectric phase transition at Tc = 338 K,
      changing from the chiral space group of P212121 to polar Pna21 upon heating.
      Crystal structure analyses reveal that an unusual thermally activated
      conformation change of the piperidinium cations affords the driving force to the
      phase transition of 1. That is, organic piperidinium moieties display a chairlike
      conformation below Tc, which transforms to a boatlike structure above Tc. Such an
      unprecedented change is strongly coupled to the dielectric transition along with
      notable steplike anomalies, which suggest that 1 could be used as a potential
      switchable dielectric material. Besides, the temperature-dependent conductivity
      and theoretical analysis of its electronic structure disclose the semiconducting
      behavior of 1. This study paves the pathway to the design of new lead-free
      semiconducting perovskites with targeted properties for optoelectronic
      application.

PMID- 29068202
TI  - Whole-Cell Detection of C-P Bonds in Bacteria.
AB  - Naturally produced molecules possessing a C-P bond, such as phosphonates and
      phosphinates, remain vastly underexplored. Although success stories like
      fosfomycin have reinvigorated small molecule phosphonate discovery efforts,
      bioinformatic analyses predict an enormous unexplored biological reservoir of C-P
      bond-containing molecules, including those attached to complex macromolecules.
      However, high polarity, a lack of chromophores, and complex macromolecular
      association impede phosphonate discovery and characterization. Here we detect
      widespread transcriptional activation of phosphonate biosynthetic machinery
      across diverse bacterial phyla and describe the use of solid-state nuclear
      magnetic resonance to detect C-P bonds in whole cells of representative Gram
      negative and Gram-positive bacterial species. These results suggest that
      phosphonate tailoring is more prevalent than previously recognized and set the
      stage for elucidating the fascinating chemistry and biology of these
      modifications.

PMID- 29068203
TI  - Rhodium-Catalyzed sp2 C-H Acetoxylation of N-Aryl Azaindoles/N-Heteroaryl
      Indolines.
AB  - A silver- and copper-free rhodium-catalyzed C-H acetoxylation reaction of
      azaindoles has been achieved at near ambient temperature employing PIDA as a
      nonmetallic acetoxy source. The method is highly selective, efficient, and
      scalable and requires acetic anhydride as the sole additive. The scope of the
      reaction has been successfully tested with a wide array of medicinally important
      heterocyclic scaffolds with diverse functional group tolerance. A series of
      kinetic experiments was conducted to gain detailed insight into the reaction
      mechanism. The methodology developed could be successfully expanded for C7
      acetoxylation of indoline derivatives using pyrimidine as a detachable directing
      group for the synthesis of 7-hydroxyindole.

PMID- 29068204
TI  - Molecule-Confined Engineering toward Superconductivity and Ferromagnetism in Two
      Dimensional Superlattice.
AB  - Superconductivity is mutually exclusive with ferromagnetism, because the
      ferromagnetic exchange field is often destructive to superconducting pairing
      correlation. Well-designed chemical and physical methods have been devoted to
      realize their coexistence only by structural integrity of inherent
      superconducting and ferromagnetic ingredients. However, such coexistence in
      freestanding structure with nonsuperconducting and nonferromagnetic components
      still remains a great challenge up to now. Here, we demonstrate a molecule
      confined engineering in two-dimensional organic-inorganic superlattice using a
      chemical building-block approach, successfully realizing first freestanding
      coexistence of superconductivity and ferromagnetism originated from electronic
      interactions of nonsuperconducting and nonferromagnetic building blocks. We
      unravel totally different electronic behavior of molecules depending on spatial
      confinement: flatly lying Co(Cp)2 molecules in strongly confined SnSe2
      interlayers weaken the coordination field, leading to spin transition to form
      ferromagnetism; meanwhile, electron transfer from cyclopentadienyls to the Se-Sn
      Se lattice induces superconducting state. This entirely new class of coexisting
      superconductivity and ferromagnetism generates a unique correlated state of Kondo
      effect between the molecular ferromagnetic layers and inorganic superconducting
      layers. We anticipate that confined molecular chemistry provides a newly powerful
      tool to trigger exotic chemical and physical properties in two-dimensional
      matrixes.

PMID- 29068205
TI  - Kinetic Isotope Effects Provide Experimental Evidence for Proton Tunneling in
      Methylammonium Lead Triiodide Perovskites.
AB  - The occurrence of proton tunneling in MAPbI3 hybrid organic inorganic perovskites
      is demonstrated through the effect of isotopic labeling of the methylammonium
      (MA) component on the dielectric permittivity response. Deuteration of the
      ammonium group results in the acceleration of proton migration (inverse primary
      isotope effect), whereas deuteration of the methyl group induces a normal
      secondary isotope effect. The activation energies for proton migration are
      calculated to be 50 and 27 meV for the tetragonal and orthorhombic phases,
      respectively, which decrease upon deuteration of the ammonium group. The low
      activation barrier and the deviation from unity of the ratio of the pre
      exponential factors (AH/AD = 0.3-0.4) are consistent with a tunneling mechanism
      for proton migration. Deuteration of the PEDOT:PSS hole transport layer results
      in a behavior that is intermediate between that of the deuterated and
      undeuterated perovskite, due to extrinsic ion migration between the two
      materials.

PMID- 29068206
TI  - Slow Magnetic Relaxation in Intermediate Spin S = 3/2 Mononuclear Fe(III)
      Complexes.
AB  - Magneto-structural correlation studies of mononuclear intermediate S = 3/2
      Fe(III) complexes, (PMe3)2FeCl3 (1) and (PMe2Ph)2FeCl3 (2), demonstrate the
      influence of local symmetry on magnetic anisotropy. Symmetric compound 1 is
      characterized by a zero-field splitting (ZFS) parameter of D = -50(2) cm-1,
      leading to the observation of slow magnetic relaxation with an energy barrier of
      81 cm-1 along with magnetic hysteresis up to 4 K, whereas symmetrically perturbed
      compound 2 displays a much reduced ZFS parameter of D = -17(1) cm-1 and energy
      barrier of Ueff = 46 cm-1.

PMID- 29068207
TI  - Large Negative Linear Compressibility in InH(BDC)2 from Framework Hinging.
AB  - Materials with negative linear compressibility (NLC) counterintuitively expand
      along one specific direction coupled to the volume reduction when compressed
      uniformly. NLC with a large value is desired for compression and materials
      science. However, NLC is generally smaller than -20 TPa-1. High-pressure X-ray
      diffraction experiments reveal that the beta-quartz-like InH(BDC)2 generates an
      extreme NLC (-62.4 TPa-1) by framework hinging. InH(BDC)2 is much safer and lower
      cost than Au+/Ag+ and CN--containing materials that dominated the fields of large
      NLC. This work reconfirms that a negative thermal expansion flexible framework
      could likely exhibit large NLC. Moreover, a large NLC could be anticipated to
      arise from beta-quartz-like or related frameworks composed of rigid linear
      ligands and flexible framework angles.

PMID- 29068208
TI  - Well-Defined Silanols in the Structure of the Calcined High-Silica Zeolite SSZ
      70: New Understanding of a Successful Catalytic Material.
AB  - The structure of the calcined form of the high-silica zeolite SSZ-70 has been
      elucidated by combining synchrotron X-ray powder diffraction (XRPD), high
      resolution transmission electron microscopy (HRTEM), and two-dimensional (2D)
      dynamic nuclear polarization (DNP)-enhanced NMR techniques. The framework
      structure of SSZ-70 is a polytype of MWW and can be viewed as a disordered ABC
      type stacking of MWW-layers. HRTEM and XRPD simulations show that the stacking
      sequence is almost random, with each layer being shifted by +/-1/3 along the
      ?110? direction with respect to the previous one. However, a small preponderance
      of ABAB stacking could be discerned. DNP-enhanced 2D 29Si{29Si} J-mediated NMR
      analyses of calcined Si-SSZ-70 at natural 29Si isotopic abundance (4.7%)
      establish the through-covalent-bond 29Si-O-29Si connectivities of distinct Si
      sites in the framework. The DNP-NMR results corroborate the presence of MWW
      layers and, more importantly, identify two distinct types of Q3 silanol species
      at the surfaces of the interlayer regions. In the first, an isolated silanol
      group protrudes into the interlayer space pointing toward the pocket in the
      adjacent layer. In the second, the surrounding topology is the same, but the
      isolated -SiOH group is missing, leaving a nest of three Si-O-H groups in place
      of the three Si-O-Si linkages. The analyses clarify the structure of this
      complicated material, including features that do not exhibit long-range order.
      With these insights, the novel catalytic behavior of SSZ-70 can be better
      understood and opportunities for enhancement recognized.

PMID- 29068210
TI  - Direct Conversion of CO2 to alpha-Farnesene Using Metabolically Engineered
      Synechococcus elongatus PCC 7942.
AB  - Direct conversion of carbon dioxide (CO2) to value-added chemicals by engineering
      of cyanobacteria has received attention as a sustainable strategy in food and
      chemical industries. Herein, Synechococcus elongatus PCC 7942, a model
      cyanobacterium, was engineered to produce alpha-farnesene from CO2. As a result
      of the lack of farnesene synthase (FS) activity in the wild-type cyanobacterium,
      we metabolically engineered S. elongatus PCC 7942 to express heterologous FS from
      either Norway spruce or apple fruit, resulting in detectable peaks of alpha
      farnesene. To enhance alpha-farnesene production, an optimized methylerythritol
      phosphate (MEP) pathway was introduced in the farnesene-producing strain to
      supply farnesyl diphosphate. Subsequent cyanobacterial culture with a dodecane
      overlay resulted in photosynthetic production of alpha-farnesene (4.6 +/- 0.4
      mg/L in 7 days) from CO2. To the best of our knowledge, this is the first report
      of the photosynthetic production of alpha-farnesene from CO2 in the unicellular
      cyanobacterium S. elongatus PCC 7942.

PMID- 29068209
TI  - Quantifying Binding of Ethylene Oxide-Propylene Oxide Block Copolymers with Lipid
      Bilayers.
AB  - Block copolymers composed of poly(ethylene oxide) (PEO) and poly(propylene oxide)
      (PPO) have been widely used in cell membrane stabilization and permeabilization.
      To explore the mechanism of interaction between PPO-PEO block copolymers and
      lipid membranes, we have investigated how polymer structure influences the
      polymer-lipid bilayer association by varying the overall molecular weight, the
      hydrophobic and hydrophilic block lengths, and the end-group structure
      systematically, using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      unilamellar liposomes as model membranes. Pulsed-field-gradient NMR (PFG-NMR) was
      employed to probe polymer diffusion in the absence and presence of liposomes. The
      echo decay curves of free polymers in the absence of liposomes are single
      exponentials, indicative of simple translational diffusion, while in the presence
      of liposomes, the decays are biexponential, with the slower decay corresponding
      to polymers bound to liposomes. The binding percentage of polymer to the liposome
      was quantified by fitting the echo decay curves to a biexponential model. The NMR
      experiments show that increasing the total molecular weight and hydrophobicity of
      the polymer can significantly enhance the polymer-lipid bilayer association, as
      the binding percentage and liposome surface coverage both increase. We
      hypothesize that the hydrophobic PPO block inserts into the lipid bilayer due to
      the fact that little molecular exchange between bound and free polymers occurs on
      the time scale of the diffusion experiments. Additionally, as polymer
      concentration increases, the liposome surface coverage increases and approaches a
      limit. These results demonstrate that PFG-NMR is a simple yet powerful method to
      quantify interactions between polymers and lipid bilayers.

PMID- 29068211
TI  - Correction to Combined Effects of Early Season Leaf Removal and Climatic
      Conditions on Aroma Precursors in Sauvignon Blanc Grapes.

PMID- 29068213
TI  - Highly Sensitive Ratiometric Fluorescent Sensor for Trinitrotoluene Based on the
      Inner Filter Effect between Gold Nanoparticles and Fluorescent Nanoparticles.
AB  - In this work, we developed a simple and sensitive ratiometric fluorescent assay
      for sensing trinitrotoluene (TNT) based on the inner filter effect (IFE) between
      gold nanoparticles (AuNPs) and ratiometric fluorescent nanoparticles (RFNs),
      which was designed by hybridizing green emissive carbon dots (CDs) and red
      emissive quantum dots (QDs) into a silica sphere as a fluorophore pair. AuNPs in
      their dispersion state can be a powerful absorber to quench CDs, while the
      aggregated AuNPs can quench QDs in the IFE-based fluorescent assays as a result
      of complementary overlap between the absorption spectrum of AuNPs and emission
      spectrum of RFNs. As a result of the fact that TNT can induce the aggregation of
      AuNPs, with the addition of TNT, the fluorescent of QDs can be quenched, while
      the fluorescent of CDs would be recovered. Then, ratiometric fluorescent
      detection of TNT is feasible. The present IFE-based ratiometric fluorescent
      sensor can detect TNT ranging from 0.1 to 270 nM, with a detection limit of 0.029
      nM. In addition, the developed method was successfully applied to investigate TNT
      in water and soil samples with satisfactory recoveries ranging from 95 to 103%,
      with precision below 4.5%. The simple sensing approach proposed here could
      improve the sensitivity of colorimetric analysis by changing the ultraviolet
      analysis to ratiometric fluorescent analysis and promote the development of a
      dual-mode detection system.

PMID- 29068212
TI  - Carbene and Acid Cooperative Catalytic Reactions of Aldehydes and o
      Hydroxybenzhydryl Amines for Highly Enantioselective Access to Dihydrocoumarins.
AB  - A highly enantioselective method for quick access to dihydrocoumarins is
      reported. The reaction involves a cooperative catalytic process with carbene and
      in situ generated Bronsted acid as the catalysts. alpha-Chloro aldehyde and
      readily available and stable o-hydroxybenzhydryl amine substrates were used to
      generate reactive azolium ester enolate and ortho-quinone methide (o-QM)
      intermediates, respectively, to form dihydrocoumarins with exceptionally high
      diastereo- and enantioselectivities. The catalytic reaction products can be
      easily transformed to valuable pharmaceuticals and bioactive molecules.

PMID- 29068214
TI  - Electronic and Optical Properties of Two-Dimensional GaN from First-Principles.
AB  - Gallium nitride (GaN) is an important commercial semiconductor for solid-state
      lighting applications. Atomically thin GaN, a recently synthesized two
      dimensional material, is of particular interest because the extreme quantum
      confinement enables additional control of its light-emitting properties. We
      performed first-principles calculations based on density functional and many-body
      perturbation theory to investigate the electronic, optical, and excitonic
      properties of monolayer and bilayer two-dimensional (2D) GaN as a function of
      strain. Our results demonstrate that light emission from monolayer 2D GaN is
      blueshifted into the deep ultraviolet range, which is promising for sterilization
      and water-purification applications. Light emission from bilayer 2D GaN occurs at
      a similar wavelength to its bulk counterpart due to the cancellation of the
      effect of quantum confinement on the optical gap by the quantum-confined Stark
      shift. Polarized light emission at room temperature is possible via uniaxial in
      plane strain, which is desirable for energy-efficient display applications. We
      compare the electronic and optical properties of freestanding two-dimensional GaN
      to atomically thin GaN wells embedded within AlN barriers in order to understand
      how the functional properties are influenced by the presence of barriers. Our
      results provide microscopic understanding of the electronic and optical
      characteristics of GaN at the few-layer regime.

PMID- 29068215
TI  - Access to Substituted Propenoic Acids via Rh(III)-Catalyzed C-H Allylation of
      (Hetero)Arenes with Methyleneoxetanones.
AB  - An efficient synthesis of disubstituted acrylic acids has been realized via
      Rh(III)-catalyzed C-H activation of (hetero)arenes and coupling with four
      membered methyleneoxetanones under redox-neutral conditions. In most cases, the
      reactions are silver-free, and the products are exclusively E-selective with a
      broad substrate scope. The transformation proceeds via ortho C-H activation
      followed by selective olefin insertion and beta-oxygen elimination.

PMID- 29068216
TI  - Tumor Progression of Non-Small Cell Lung Cancer Controlled by Albumin and
      Micellar Nanoparticles of Itraconazole, a Multitarget Angiogenesis Inhibitor.
AB  - Itraconazole (ITA), an old and widely prescribed antifungal drug with excellent
      safety profile, has more recently been demonstrated to be a multitarget
      antiangiogenesis agent affecting multiple angiogenic stimulatory signals and
      pathways, including vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), vascular endothelial growth factor receptor 2 (VEGFR2)
      glycosylation, and mammalian target of rapamycin (mTOR). In this study, we
      developed two nanoparticle formulations, i.e., polymer micelles (IP2K) and
      albumin nanoparticles (IBSA), to solubilize the extremely hydrophobic and
      insoluble ITA to allow intravenous administration and pharmacokinetics
      (PK)/pharmacodynamics (PD) comparisons. Although none of the formulations showed
      strong antiproliferation potency against non-small cell lung cancer (NSCLC) cells
      in vitro, when administrated at the equivalent ITA dose to a NSCLC patient
      derived xenograft (PDX) model, IBSA retarded while IP2K accelerated the tumor
      growth. We attributed the cause of this paradox to formulation-dependent PK and
      vascular manipulation: IBSA demonstrated a more sustained PK with a Cmax of 60
      70% and an AUC ~2 times of those of IP2K, and alleviated the tumor hypoxia
      presumably through vascular normalization. In contrast, the high Cmax of IP2K
      elevated tumor hypoxia through a strong angiogenesis inhibition, which could have
      aggravated cancer aggressiveness and accelerated tumor growth. Furthermore, IBSA
      induced minimal hepatic and hematologic toxicities compared to IP2K and
      significantly enhanced the in vivo tumor inhibition activity of paclitaxel
      albumin nanoparticles when used in combination. These findings suggest that
      formulation and pharmacokinetics are critical aspects to be considered when
      designing the ITA angiogenesis therapy, and IBSA could potentially be assessed as
      a novel and safe multitarget angiogenesis therapy to be used in combination with
      other anticancer agents.

PMID- 29068217
TI  - Polyoxometalate-Surfactant Hybrids Directed Assembly of Ni3S2 into Hollow
      Microsphere as Pt-Comparable Electrocatalyst for Hydrogen Evolution Reaction in
      Alkaline Medium.
AB  - A large surface area of catalytic sites and low electric resistance are desirable
      properties for electrocatalysts that lower the overpotential required for
      electrochemical reactions, such as the hydrogen evolution reaction (HER), in this
      study. In the presence of polyoxometalate (POM) and triblock copolymer pluronic
      (P123) as a hybrid soft template, the hydrothermal sulfurization of nickel foam
      leads to the formation of a hollow microsphere, assembled from the Ni3S2 motif.
      Sonication for preparing POM+P123 hybrids, while adjusting the POM content, is an
      effective strategy for synthesizing a Pt-like electrocatalyst with excellent
      hydrogen evolution efficiency. The reason is that both sonication and optimal POM
      content can simultaneously enhance the electroactive surface area and electron
      transfer of the Ni3S2 electrocatalyst. Adopting the optimal conditions, the three
      dimensional porous network, composed of Ni3S2 hollow microspheres on the nickel
      foam, shows that the HER in an alkaline medium requires only 77 mV overpotential
      for a current density of 10 mA cm-2, with a robust long-term stability during a
      25 h test. The performance at a large current density outperforms the current
      benchmark electrocatalyst (Pt) for HER.

PMID- 29068219
TI  - Biocatalysis of a Paclitaxel Analogue: Conversion of Baccatin III to N-Debenzoyl
      N-(2-furoyl)paclitaxel and Characterization of an Amino Phenylpropanoyl CoA
      Transferase.
AB  - In this study, we demonstrate an enzyme cascade reaction using a benzoate CoA
      ligase (BadA), a modified nonribosomal peptide synthase (PheAT), a
      phenylpropanoyltransferase (BAPT), and a benzoyltransferase (NDTNBT) to produce
      an anticancer paclitaxel analogue and its precursor from the commercially
      available biosynthetic intermediate baccatin III. BAPT and NDTNBT are
      acyltransferases on the biosynthetic pathway to the antineoplastic drug
      paclitaxel in Taxus plants. For this study, we addressed the recalcitrant
      expression of BAPT by expressing it as a soluble maltose binding protein fusion
      (MBP-BAPT). Further, the preparative-scale in vitro biocatalysis of
      phenylisoserinyl CoA using PheAT enabled thorough kinetic analysis of MBP-BAPT,
      for the first time, with the cosubstrate baccatin III. The turnover rate of MBP
      BAPT was calculated for the product N-debenzoylpaclitaxel, a key intermediate to
      various bioactive paclitaxel analogues. MBP-BAPT also converted, albeit more
      slowly, 10-deacetylbaccatin III to N-deacyldocetaxel, a precursor of the
      pharmaceutical docetaxel. With PheAT available to make phenylisoserinyl CoA and
      kinetic characterization of MBP-BAPT, we used Michaelis-Menten parameters of the
      four enzymes to adjust catalyst and substrate loads in a 200-MUL one-pot
      reaction. This multienzyme network produced a paclitaxel analogue N-debenzoyl-N
      (2-furoyl)paclitaxel (230 ng) that is more cytotoxic than paclitaxel against
      certain macrophage cell types. Also in this pilot reaction, the versatile N
      debenzoylpaclitaxel intermediate was made at an amount 20-fold greater than the N
      (2-furoyl) product. This reaction network has great potential for optimization to
      scale-up production and is attractive in its regioselective O- and N-acylation
      steps that remove protecting group manipulations used in paclitaxel analogue
      synthesis.

PMID- 29068218
TI  - Design, Synthesis, and Biological Evaluation of Orally Available First-Generation
      Dual-Target Selective Inhibitors of Acetylcholinesterase (AChE) and
      Phosphodiesterase 5 (PDE5) for the Treatment of Alzheimer's Disease.
AB  - Through drug discovery strategies of repurposing and redeveloping existing drugs,
      a series of novel tadalafil derivatives were rationally designed, synthesized,
      and evaluated to seek dual-target AChE/PDE5 inhibitors as good candidate drugs
      for Alzheimer's disease (AD). Among these derivatives, 1p and 1w exhibited
      excellent selective dual-target AChE/PDE5 inhibitory activities and improved
      blood-brain barrier (BBB) penetrability. Importantly, 1w.Cit (citrate of 1w)
      could reverse the cognitive dysfunction of scopolamine-induced AD mice and
      exhibited an excellent effect on enhancing cAMP response element-binding protein
      (CREB) phosphorylation in vivo, a crucial factor in memory formation and synaptic
      plasticity. Moreover, the molecular docking simulations of 1w with hAChE and
      hPDE5A confirmed that our design strategy was rational. In summary, our research
      provides a potential selective dual-target AChE/PDE5 inhibitor as a good
      candidate drug for the treatment of AD, and it could also be regarded as a small
      molecule probe to validate the novel AD therapeutic approach in vivo.

PMID- 29068220
TI  - Three-Dimensional Graphene Foam Induces Multifunctionality in Epoxy
      Nanocomposites by Simultaneous Improvement in Mechanical, Thermal, and Electrical
      Properties.
AB  - Three-dimensional (3D) macroporous graphene foam based multifunctional epoxy
      composites are developed in this study. Facile dip-coating and mold-casting
      techniques are employed to engineer microstructures with tailorable thermal,
      mechanical, and electrical properties. These processing techniques allow
      capillarity-induced equilibrium filling of graphene foam branches, creating
      epoxy/graphene interfaces with minimal separation. Addition of 2 wt % graphene
      foam enhances the glass transition temperature of epoxy from 106 to 162  degrees
      C, improving the thermal stability of the polymer composite. Graphene foam aids
      in load-bearing, increasing the ultimate tensile strength by 12% by merely 0.13
      wt % graphene foam in an epoxy matrix. Digital image correlation (DIC) analysis
      revealed that the graphene foam cells restrict and confine the deformation of the
      polymer matrix, thereby enhancing the load-bearing capability of the composite.
      Addition of 0.6 wt % graphene foam also enhances the flexural strength of the
      pure epoxy by 10%. A 3D network of graphene branches is found to suppress and
      deflect the cracks, arresting mechanical failure. Dynamic mechanical analysis
      (DMA) of the composites demonstrated their vibration damping capability, as the
      loss tangent (tan delta) jumps from 0.1 for the pure epoxy to 0.24 for ~2 wt %
      graphene foam-epoxy composite. Graphene foam branches also provide seamless
      pathways for electron transfer, which induces electrical conductivity exceeding
      450 S/m in an otherwise insulator epoxy matrix. The epoxy-graphene foam composite
      exhibits a gauge factor as high as 4.1, which is twice the typical gauge factor
      for the most common metals. Simultaneous improvement in thermal, mechanical, and
      electrical properties of epoxy due to 3D graphene foam makes epoxy-graphene foam
      composite a promising lightweight and multifunctional material for aiding load
      bearing, electrical transport, and motion sensing in aerospace, automotive,
      robotics, and smart device structures.

PMID- 29068221
TI  - Au/Graphene Oxide Nanocomposite Synthesized in Supercritical CO2 Fluid as Energy
      Efficient Lubricant Additive.
AB  - Au nanoparticles are successfully decorated onto graphene oxide (GO) sheets with
      the aid of supercritical carbon dioxide (ScCO2) fluid. The synthesized
      nanocomposite (Sc-Au/GO) was characterized by X-ray diffraction (XRD), Raman
      spectroscopy, thermal gravimetric analysis (TGA), and transmission electron
      microscopy (TEM). The characterization results show that the Au nanoparticles are
      featured with face-centered cubic crystal structure and disperse well on the GO
      nanosheet surfaces with average diameters of 4-10 nm. The tribological behaviors
      of Sc-Au/GO as lubricating additive in PAO6 oil were investigated using a ball-on
      disc friction tester, and a control experiment by respectively adding GO, nano-Au
      particles, and Au/GO produced in the absence of ScCO2 was performed as well. It
      is found that Sc-Au/GO exhibits the best lubricating performances among all the
      samples tested. When 0.10 wt % Sc-Au/GO is dispersed into PAO6 oil, the friction
      coefficient and wear rate are respectively reduced by 33.6% and 72.8% as compared
      to that of the pure PAO6 oil, indicating that Sc-Au/GO is an energy efficient
      lubricant additive. A possible lubricating mechanism of Sc-Au/GO additive in PAO6
      oil has been tentatively proposed on the basis of the analyzed results of the
      worn surface examined by scanning electron microscopy (SEM), Raman spectroscopy,
      and X-ray photoelectron spectroscopy (XPS).

PMID- 29068223
TI  - Experimental Evaluation of Turbidity Impact on the Fluence Rate Distribution in a
      UV Reactor Using a Microfluorescent Silica Detector.
AB  - Turbidity is a common parameter used to assess particle concentration in water
      using visible light. However, the fact that particles play multiple roles (e.g.,
      scattering, refraction, and reflection) in influencing the optical properties of
      aqueous suspensions complicates examinations of their effects on ultraviolet (UV)
      photoreactor performance. To address this issue, UV fluence rate (FR)
      distributions in a photoreactor containing various particle suspensions (SiO2,
      MgO, and TiO2) were measured using a microfluorescent silica detector (MFSD).
      Reflectance of solid particles, as well as transmittance and scattering
      properties of the suspensions were characterized at UV, visible, and infrared
      (IR) wavelengths. The results of these measurements indicated that the optical
      properties of all three particle types were similar at visible and IR
      wavelengths, but obvious differences were evident in the UV range. The FR results
      indicated that for turbidity associated with SiO2 and MgO suspensions, the
      weighted average FR (WAFR) increased relative to deionized water. These increases
      were attributed to low particle photon absorption and strong scattering. In
      contrast, the WAFR values decreased with increasing turbidity for TiO2
      suspensions because of their high particle photon absorption and low scattering
      potential. The findings also indicate that measurements of scattering and
      transmittance at UV wavelengths can be used to quantify the effects of turbidity
      on UV FR distributions.

PMID- 29068222
TI  - Stereoselective Deuteration in Aspartate, Asparagine, Lysine, and Methionine
      Amino Acid Residues Using Fumarate as a Carbon Source for Escherichia coli in
      D2O.
AB  - Perdeuteration with selective 1H,13C-enrichment of methyl groups has enabled
      solution NMR studies of large (>30 kDa) protein systems. However, we propose that
      for all non-methyl positions, only magnetization originating from 1H-12C groups
      is sufficiently long-lived, and it can be transferred via through-space NOEs to
      slowly relaxing 1H-15N or 1H-13C methyl groups to achieve multidimensional
      solution NMR. We demonstrate stereoselective 1H,12C-labeling by adding relatively
      inexpensive unlabeled carbon sources to Escherichia coli growth media in D2O.
      Using our model system, a mutant WW domain from human Pin1, we compare
      deuteration patterns in 19 amino acids (all except cysteine). Protein grown using
      glucose as the sole carbon source had high levels of protonation in aromatic
      rings and the Hbeta positions of serine and tryptophan. In contrast, using our
      FROMP media (fumarate, rhamnose, oxalate, malonate, pyruvate), stereoselective
      protonation of Hbeta2 with deuteration at Halpha and Hbeta3 was achieved in Asp,
      Asn, Lys, and Met residues. In solution NMR, stereospecific chemical shift
      assignments for Hbeta are typically obtained in conjunction with chi1 dihedral
      angle determinations using 3-bond J-coupling (3JN-Hbeta, 3JCO-Hbeta, 3JHalpha
      Hbeta) experiments. However, due to motional averaging, the assumption of a pure
      rotameric state can yield incorrect chi1 dihedral angles with incorrect
      stereospecific assignments. This was the case for three residues in the Pin1 WW
      domain (Lys28, Met30, and Asn44). Thus, stereoselective 1H,12C-labeling will be
      useful not only for NMR studies of large protein systems, but also for
      determining side chain rotamers and dynamics in any protein system.

PMID- 29068224
TI  - Excited-State Decay Pathways of Tris(bidentate) Cyclometalated Ruthenium(II)
      Compounds.
AB  - The synthesis, electrochemistry, and photophysical characterization are reported
      for 11 tris(bidentate) cyclometalated ruthenium(II) compounds, [Ru(N^N)2(C^N)]+.
      The electrochemical and photophysical properties were varied by the addition of
      substituents on the 2,2'-bipyridine, N^N, and 2-phenylpyridine, C^N, ligands with
      different electron-donating and -withdrawing groups. The systematic tuning of
      these properties offered a tremendous opportunity to investigate the origin of
      the rapid excited-state decay for these cyclometalated compounds and to probe the
      accessibility of the dissociative, ligand-field (LF) states from the metal-to
      ligand charge-transfer (MLCT) excited state. The photoluminescence quantum yield
      for [Ru(N^N)2(C^N)]+ increased from 0.0001 to 0.002 as more electron-withdrawing
      substituents were added to C^N. An analogous substituent dependence was observed
      for the excited-state lifetimes, tauobs, which ranged from 3 to 40 ns in neat
      acetonitrile, significantly shorter than those for their [Ru(N^N)3]2+ analogues.
      The excited-state decay for [Ru(N^N)2(C^N)]+ was accelerated because of an
      increased vibronic overlap between the ground- and excited-state wavefunctions
      rather than an increased electronic coupling as revealed by a comparison of the
      Franck-Condon factors. The radiative (kr) and non-radiative (knr) rate constants
      of excited-state decay were determined to be on the order of 104 and 107-108 s-1,
      respectively. For sets of [Ru(N^N)2(C^N)]+ compounds functionalized with the same
      N^N ligand, knr scaled with excited-state energy in accordance with the energy
      gap law. Furthermore, an Arrhenius analysis of tauobs for all of the compounds
      between 273 and 343 K was consistent with activated crossing into a single,
      fourth 3MLCT state under the conditions studied with preexponential factors on
      the order of 108-109 s-1 and activation energies between 300 and 1000 cm-1. This
      result provides compelling evidence that LF states are not significantly
      populated near room temperature unlike many ruthenium(II) polypyridyl compounds.
      On the basis of the underlying photophysics presented here for [Ru(N^N)2(C^N)]+,
      molecules of this type represent a robust class of compounds with built-in design
      features that should greatly enhance the molecular photostability necessary for
      photochemical and photoelectrochemical applications.

PMID- 29068225
TI  - Fabrication of Flexible Transparent Electrode with Enhanced Conductivity from
      Hierarchical Metal Grids.
AB  - Flexible transparent conductive electrodes (FTCEs) are essential components for
      numerous optoelectronic devices. In this work, we have fabricated the
      hierarchical metal grids (HMG) FTCEs by a facile and low-cost, near-field
      photolithography strategy. Compared to normal metal grids (MG), the HMG structure
      can provide distinctly increased conductivity of the electrode yet without
      obvious reduction of the optical transmittance. This HMG sample possesses
      excellent optoelectronic performance and high mechanical flexibility, making it a
      promising component for practical applications.

PMID- 29068226
TI  - Sequence Control as a Powerful Tool for Improving the Selectivity of
      Antimicrobial Polymers.
AB  - Antimicrobial polymers appear as a promising alternative to tackle the current
      development of bacterial resistance against conventional antibiotics as they rely
      on bacterial membrane disruption. This study investigates the effect of
      segmentation of hydrophobic and cationic functionalities on antimicrobial
      polymers over their selectivity between bacteria and mammalian cells. Using RAFT
      technology, statistical, diblock, and highly segmented multiblock copolymers were
      synthesized in a controlled manner. Polymers were analyzed by HPLC, and the
      segmentation was found to have a significant influence on their overall
      hydrophobicity. In addition, the amount of incorporated cationic comonomer was
      varied to yield a small library of bioactive macromolecules. The antimicrobial
      properties of these compounds were probed against pathogenic bacteria
      (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and
      Staphylococcus epidermidis), and their biocompatibility was tested using
      hemolysis and erythrocyte aggregation assays, as well as mammalian cell viability
      assays. In all cases, diblock and multiblock copolymers were found to outperform
      statistical copolymers, and for polymers with a low content of cationic
      comonomer, the multiblock showed a tremendously increased selectivity for P.
      aeruginosa and S. epidermidis compared to its statistical and diblock analogue.
      This work highlights the remarkable effect of segmentation on both the physical
      properties of the materials as well as their interaction with biological systems.
      Due to the outstanding selectivity of multiblock copolymers toward certain
      bacteria strains, the presented materials are a promising platform for the
      treatment of infections and a valuable tool to combat antimicrobial resistance.

PMID- 29068227
TI  - Intrinsic Thermal Management Capabilities of Flexible Metal-Organic Frameworks
      for Carbon Dioxide Separation and Capture.
AB  - We show that flexible metal-organic frameworks (MOFs) exhibiting "gate
      openings/closings" for CO2 can intrinsically suppress the exothermic heat
      released by adsorption and the endothermic heat gained by desorption, both of
      which reduce the working capacity of CO2 in a separation process under near
      adiabatic conditions. We use the elastic layer-structured metal-organic framework
      11 (ELM-11) [Cu(4,4'-bipyridine)2(BF4)2], which exhibits a two-step gate
      adsorption isotherm, as a model system for flexible MOFs, and perform free energy
      analyses with the aid of grand canonical Monte Carlo simulations for ELM-11
      structures that were determined by the Rietveld method using in situ synchrotron
      X-ray powder diffraction data. We demonstrate that the thermal management
      capabilities of ELM-11 showing the two-step gating for CO2 at lower and higher
      pressures are nearly identical and quite effective (41% and 44% at 298 K,
      respectively). Moreover, we show that ELM-11 has an extremely high CO2
      selectivity for both CO2/N2 and CO2/CH4 mixtures at 298 K that, in addition to
      the intrinsic thermal management capability, is a crucial factor for application
      to carbon capture and storage (CCS). The multigate closing pressures of ELM-11
      are not necessarily matched to the operating pressures used in CCS; however, our
      findings, and perspectives based on free energy analyses regarding modification
      of the host framework structure to tune the gating pressure, suggest that
      flexible MOFs exhibiting multigate openings/closings are promising materials for
      further development into systems with intrinsic thermal management mechanisms for
      CCS applications.

PMID- 29068228
TI  - Palladium-Catalyzed Removable 8-Aminoquinoline Assisted Chemo- and Regioselective
      Oxidative sp2-C-H/sp3-C-H Cross-Coupling of Ferrocene with Toluene Derivatives.
AB  - The coupling of the C(sp2)-H bond of ferrocene with toluene avoiding in situ
      functionalization of both coupling partners has been achieved using palladium and
      iron dual catalysis. This cross oxidative coupling features regioselectivity to
      primary and secondary C(sp3)-H bonds and chemoselectivity toward the -C(sp3)-H
      over C-I bond of toluene with gram-scale production. It seems Fe(II) catalyst not
      only stabilizes the generated benzyl radical but also tames its oxidizing
      behavior, and consequently transfers it to the palladacycle for C-C coupling.

PMID- 29068229
TI  - Direct Observation of a Photochemical Alkyne-Allene Reaction and of a Twisted and
      Rehybridized Intramolecular Charge-Transfer State in a Donor-Acceptor Dyad.
AB  - The excited-state dynamics of an aniline-triazine electron donor-acceptor dyad
      with an alkyne spacer has been investigated using a combination of ultrafast
      broadband mid-IR and visible transient absorption and fluorescence
      spectroscopies. The transient IR data reveal the occurrence of an efficient
      alkyne to allene isomerization of the spacer with a time constant increasing from
      a few hundreds of femtoseconds to a few picoseconds with solvent viscosity. This
      process is faster than the vibrational cooling of the Franck-Condon excited
      state, indicative of nonequilibrium dynamics. The transient electronic absorption
      and fluorescence data evidence that this transformation is accompanied by a
      charge separation between the donor and the acceptor subunits. The allene
      character of the spacer implies an orthogonal orientation of the donor and
      acceptor moieties, similar to that proposed for twisted intramolecular charge
      transfer states. Such states are often invoked in the excited-state dynamics of
      donor-acceptor dyads, but their involvement could never be unambiguously
      evidenced spectroscopically. The alkyne-allene isomerization involves not only a
      torsional motion but also a bending of the molecule due to the sp to sp2
      rehybridization of one of the alkyne carbon atoms. This twisted and rehybridized
      intramolecular charge transfer ("TRICT") state decays back to the planar and
      linear alkyne ground state on a time scale decreasing from a few hundred to ten
      picoseconds upon going from weakly to highly polar solvents. The different
      solvent dependencies reveal that the dynamics of the allene buildup are
      controlled by the structural changes, whereas the decay is limited by the charge
      recombination step.

PMID- 29068230
TI  - Binding of Alkali Metal Ions with 1,3,5-Tri(phenyl)benzene and 1,3,5
      Tri(naphthyl)benzene: The Effect of Phenyl and Naphthyl Ring Substitution on
      Cation-pi Interactions Revealed by DFT Study.
AB  - The effect of substitution of phenyl and naphthyl rings to benzene was examined
      to elucidate the cation-pi interactions involving alkali metal ions with 1,3,5
      tri(phenyl)benzene (TPB) and 1,3,5-tri(naphthyl)benzene (TNB). Benzene, TPB, and
      four TNB isomers (with alphaalphaalpha, alphaalphabeta, alphabetabeta, and
      betabetabeta types of fusion) and their complexes with Li+, Na+, K+, Rb+, and Cs+
      were optimized using DFT approach with B3LYP and M06-2X functionals in
      conjunction with the def2-QZVP basis set. Higher relative stability of
      beta,beta,beta-TNB over alpha,alpha,alpha-TNB can be attributed to peri
      repulsion, which is defined as the nonbonding repulsive interaction between
      substituents in the 1- and the 8-positions on the naphthalene core. Binding
      energies, distances between ring centroid and the metal ions, and the distance to
      metal ions from the center of other six-membered rings were compared for all
      complexes. Our computational study reveals that the binding affinity of alkali
      metal cations increases significantly with the 1,3,5-trisubstitution of phenyl
      and naphthyl rings to benzene. The detailed computational analyses of geometries,
      partial charges, binding energies, and ligand organization energies reveal the
      possibility of favorable C-H...M+ interactions when a alpha-naphthyl group exists
      in complexes of TNB structures. Like benzene-alkali metal ion complexes, the
      binding affinity of metal ions follows the order: Li+ > Na+ > K+ > Rb+ > Cs+ for
      any considered 1,3,5-trisubstituted benzene systems. In case of TNB, we found
      that the strength of interactions increases as the fusion point changes from
      alpha to beta position of naphthalene.

PMID- 29068231
TI  - Innovation in Small-Molecule-Druggable Chemical Space: Where are the Initial
      Modulators of New Targets Published?
AB  - It is well-established that the number of publications of novel small molecule
      modulators, and their associated targets, has increased over the years. This work
      focuses on publishing trends over the years with a particular focus on the
      comparison between patents and scientific literature which is accessible via the
      ChEMBL and GOSTAR databases. More precisely, the patents and scientific
      literature associated with bioactive molecules and their target annotations have
      been compared to identify where novelty (in the meaning of the first modulator of
      a protein target) originated from. Comparing the published date of the first
      small molecule modulator published in literature and patents for a particular
      target (with either identical or different structure) shows that modulators are
      usually published in both scientific literature and in patents (45%), or in
      scientific literature alone (51%), but rarely in patents only. When looking at
      the time when first modulators are published in both sources, 65% of the time
      they are disseminated in literature first. Finally, when analyzing just the novel
      small molecule modulators, regardless of the protein targets they have been
      published with, those structures representing novel chemistry tend to be
      published in patents first 61% of the time.

PMID- 29068232
TI  - Tunable Heck-Mizoroki Reaction of Dibromonaphthalene Diimide with Aryl Ethylenes:
      Design, Synthesis, and Characterization of Coplanar NDI-Based Conjugated
      Molecules.
AB  - Rational design of coplanar NDI-based conjugated molecules was achieved by
      covalently connecting naphthalene diimide (NDI) units with aryl (Ar) groups
      through vinylene (V) linkers via Heck-Mizoroki reaction. Two series of products,
      diolefination products (ArVNDIVAr) and hydroxylated and mono-olefination products
      (HONDIVAr), can be obtained, respectively, in moderate to excellent yields (45
      90%) under controlled conditions, in which catalyst and base play the key roles.
      Density functional theory calculation discloses the outstanding planarity of the
      two types of products. Large bathochromic shifts are observed in both the
      absorbance and photoluminescence spectra of the HONDIVAr (144 and 229 nm) and
      ArVNDIVAr (180 and 242 nm) pi-systems. Bathochromic shifts can be adjusted within
      the broad wavelength range by introducing 4'-substituents, either electron
      withdrawing group (NO2) or electron-donating group (NMe2), in the phenyl group of
      aryl ethylenes. ArVNDIVArs show bigger bathochromic shifts than HONDIVArs.

PMID- 29068233
TI  - Subclinical target organ damage in subjects with different components of
      metabolic syndrome.
AB  - BACKGROUND: To assess the association of metabolic syndrome (MS) and its
      components with target organ damage in a follow-up study of relatively healthy
      bank employers. METHODS: Out of 1600 random samples of office workers in Saint
      Petersburg (Russia), a group of 383 participants with at least one component of
      MS and without cardiovascular complications was selected (mean age 46.6 +/- 9.0
      years, 214 females (64.6%)). Follow-up visit was performed in 331 subjects.
      Target organ damage (TOD) was assessed by echocardiography, carotid ultrasound,
      applanational tonometry, brachial-ankle index, and urine albumin excretion
      measurements. Anthropometry, vital signs, and biochemistry were performed
      according to standard protocols. RESULTS: Presence of MS was not associated with
      higher probability of TOD. Multiple linear regression revealed significant
      association of all markers of TOD with older age. Hypertension was a significant
      predictor of left ventricular hypertrophy (LVH), increased arterial stiffness,
      and early signs of carotid atherosclerosis in logistic regression adjusted for
      age and gender. During follow-up, proportion of patients with LVH significantly
      decreased (from 46.7% to 32.9%, r = 0.003) and prevalence of patients with IMT >
      0.09 sm increased (from 24.5% to 44.1%, p < 0.001) accompanying by significant
      declining of office blood pressure (BP) and total cholesterol. CONCLUSIONS: MS
      per se is not related to increased probability to TOD. Hypertension, female
      gender, and older age are main determinants of subclinical changes. After 2-years
      follow-up, significant LVH and renal damage regression was observed probably
      owing to BP reduction. Alternatively, early signs of carotid atherosclerosis
      increase with aging despite decreasing of the prevalence of hypercholesterolemia.

PMID- 29068235
TI  - Comment: Rifampin-Resistant Staphylococcus aureus Bacteremia in a Patient on
      Chronic Rifaximin.

PMID- 29068234
TI  - Protective efficacy of antidiarrheal agents in a permeability model of
      Escherichia coli-infected CacoGoblet(r) cells.
AB  - AIM: To compare the protective efficacy of gelatine tannate/probiotic with other
      antidiarrheal agents in Escherichia coli-inoculated CacoGoblet(r) cells. METHODS:
      Four test compounds - gelatine tannate plus inactivated probiotic, diosmectite,
      probiotic mixture and Saccharomyces boulardii - were added to E. coli-infected
      CacoGoblet cells. After 1 and 24 h, transepithelial electrical resistance was
      measured and a lucifer yellow assay performed. RESULTS: Gelatine
      tannate/probiotic markedly increased transepithelial electrical resistance by
      123.1% (at 1 h) and 149.5% (at 24 h), and produced paracellular flux values of
      0.41% (1 h) and 1.34% (24 h), which were considerably less than the E. coli
      invasion value (2.41%). CONCLUSION: The protective efficacy of gelatine
      tannate/probiotic against E. coli-induced reduction of membrane integrity
      manifests early and is maintained for 24 h.

PMID- 29068237
TI  - Insights into the evolution of the mutational resistome of Pseudomonas aeruginosa
      in cystic fibrosis.

PMID- 29068238
TI  - Influence of magnetopriming on germination, growth, physiology, oil and essential
      contents of cumin (Cuminum cyminum L.).
AB  - An environment friendly technique is desirable for enhancing of crop production.
      In this study, seeds of cumin (Cuminum cyminum L.) Yazd accession were treated
      with 0, 150 mT, 250 mT, 500 mT and 1 T magnetic field strengths for min and
      germination parameters were determined. All of the treatments improved
      germination parameters and seedling growth as compared with the control. However,
      500 and 150 mT were the most effective treatments and thus selected for field
      studies. Seeds were exposed to 150 mT and 500 mT static magnetic field of
      strengths for 12 min, planted in the field during 2010-2012 in Isfahan, Iran.
      Static magnetic field treatment shortened the days to emergence, flowering and
      maturity, increased chlorophyll and reduced proline contents. Highest biological,
      seed and essential oil yield, oil content, and oil yield were recorded under 500
      mT followed by 150 mT and control, respectively. The results suggested that the
      pretreatment of cumin seeds with static magnetic field can improve germination,
      growth and oil and essential contents of the cumin seed under the field.

PMID- 29068239
TI  - A Phytophthora palmivora Extracellular Cystatin-Like Protease Inhibitor Targets
      Papain to Contribute to Virulence on Papaya.
AB  - Papaya fruits, stems, and leaves are rich in papain, a cysteine protease that has
      been shown to mediate plant defense against pathogens and insects. Yet the
      oomycete Phytophthora palmivora is a destructive pathogen that infects all parts
      of papaya plants, suggesting that it has evolved cysteine protease inhibitors to
      inhibit papain to enable successful infection. Out of five putative extracellular
      cystatin-like cysteine protease inhibitors (PpalEPICs) from P. palmivora
      transcriptomic sequence data, PpalEPIC8 appeared to be unique to P. palmivora and
      was highly induced during infection of papaya. Purified recombinant PpalEPIC8
      strongly inhibited papain enzyme activity, suggesting that it is a functional
      cysteine protease inhibitor. Homozygous PpalEPIC8 mutants were generated using
      CRISPR/Cas9-mediated gene editing via Agrobacterium-mediated transformation
      (AMT). Increased papain sensitivity of in-vitro growth and reduced pathogenicity
      during infection of papaya fruits were observed for the mutants compared with the
      wild-type strain, suggesting that PpalEPIC8, indeed, plays a role in P. palmivora
      virulence by inhibiting papain. This study provided genetic evidence
      demonstrating that plant-pathogenic oomycetes secrete cystatins as important
      weapons to invade plants. It also established an effective gene-editing system
      for P. palmivora by the combined use of CRISPR/Cas9 and AMT, which is expected to
      be applicable to other oomycetes.

PMID- 29068241
TI  - Strategic voices of care and compassion. Describing the mad, their afflictions
      and situations in Amsterdam and Utrecht in the seventeenth and eighteenth
      centuries.
AB  - Painting a picture of the lives of the early modern mad outside institutions has
      not yet been done in the Netherlands. However, by looking at notarial documents
      and admission requests, we can learn more about how the mad were cared for
      outside the institutions, and the impact their behaviour had on the people close
      to them. Investigating these sources for both Amsterdam and Utrecht in the
      seventeenth and eighteenth centuries has unravelled a story of community care in
      which families played a key role and used their options strategically.
      Furthermore, it has also revealed a complicated story about the way communities
      dealt with the behaviour of the mad, involving great personal struggles, breaking
      points and compassion.

PMID- 29068240
TI  - A Verticillium dahliae Extracellular Cutinase Modulates Plant Immune Responses.
AB  - Cutinases have been implicated as important enzymes during the process of fungal
      infection of aerial plant organs. The function of cutinases in the disease cycle
      of fungal pathogens that invade plants through the roots has been less studied.
      Here, functional analysis of 13 cutinase (carbohydrate esterase family 5 domain
      containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen
      Verticillium dahliae Vd991 was performed. Significant sequence divergence in
      cutinase family members was observed in the genome of V. dahliae Vd991.
      Functional analyses demonstrated that only VdCUT11, as purified protein, induced
      cell death and triggered defense responses in Nicotiana benthamiana, cotton, and
      tomato plants. Virus-induced gene silencing showed that VdCUT11 induces plant
      defense responses in Nicotiana benthamania in a BAK1 and SOBIR-dependent manner.
      Furthermore, coinfiltration assays revealed that the carbohydrate-binding module
      family 1 protein (VdCBM1) suppressed VdCUT11-induced cell death and other defense
      responses in N. benthamiana. Targeted deletion of VdCUT11 in V. dahliae
      significantly compromised virulence on cotton plants. The cutinase VdCUT11 is an
      important secreted enzyme and virulence factor that elicits plant defense
      responses in the absence of VdCBM1.

PMID- 29068242
TI  - Heterogenous origins of hyperandrogenism in the polycystic ovary syndrome in
      relation to body mass index and insulin resistance.
AB  - BACKGROUND: Insulin resistance and obesity are not universal features of
      polycystic ovary syndrome (PCOS). We planned to assess the differences between
      patients with nonobese /insulin-sensitive phenotype vs. obese/ insulin-resistant
      phenotype in terms of the potential mechanisms underlying their hyperandrogenism.
      MATERIALS AND METHODS: A total of 52 women satisfying Androgen Excess Society
      (AES) criteria were included. Hormonal and metabolic profile including prolactin,
      dehydroepiandrosterone sulfate (DHEAS), free testosterone, sex hormone binding
      globulin (SHBG), fasting plasma glucose and insulin were measured in follicular
      phase. RESULTS: DHEAS was found to be higher in the nonobese patients as compared
      to the obese (p = 0.01). There was also a strong trend for a higher DHEAS among
      patients with lower insulin resistance by homeostatic model assessment (HOMA-IR<
      2.3) (p = .06).While the total testosterone (p = .044) and SHBG (p = .007) were
      found to be lower in the more insulin-resistant group (HOMA-IR >= 2.3), the free
      testosterone levels were similar. However, the percentage of free testosterone
      was higher in the more insulin-resistant group (p = .005). CONCLUSIONS: The
      hyperandrogenic state in PCOS appears to have heterogenous origins. Nonobese
      patients with PCOS have adrenal hyperandrogenism as the underlying mechanism
      while their obese/ insulin-resistant counterparts have low SHBG and hence an
      increased fraction of free testosterone.

PMID- 29068244
TI  - Interaction between ALOX15 polymorphisms and coronary artery disease in North
      Indian population.
AB  - BACKGROUND: Coronary artery disease (CAD) is major cause of death and morbidity
      worldwide. Arachidonate 12/15-lipoxygenase (ALOX) is a member of the lipid
      peroxidizing enzyme family and implicated in the pathogenesis of atherosclerosis,
      but with contradicting results. AIM: The present study aimed to investigate the
      association of two polymorphisms in ALOX15 (rs2619112 and rs7217186) and the risk
      of CAD in North Indian population. METHODS: A total of 500 angiographically
      confirmed CAD patients and 500 control subjects of North Indian population were
      recruited in the case-control study and genotyped by PCR-RFLP. RESULTS: The data
      showed a significant association between the two polymorphisms and CAD. Multiple
      logistic regression revealed heterozygous genotype of both the polymorphisms viz.
      GA of rs2619112 and CT of rs7217186 to be associated with significant high risk
      of CAD after adjustment for confounders (p = 0.034, OR = 2.274, 95% CI (1.062
      4.870) and p = 0.000, OR = 3.407, 95% CI (2.092-5.548) respectively). Stratified
      analysis based on gender showed GA and AA of rs2619112 each significantly
      increased the risk of CAD in females (p = 0.001, OR = 13.120, CI = 2.780-61.928;
      p = 0.028, OR = 5.393, CI = 1.196-24.316 respectively) whereas only GA increased
      CAD risk in males (p = 0.005, OR = 2.277, CI = 1.290-4.020). In case of
      rs7217186, CT and TT showed a significant high risk of CAD in males (p = 0.000,
      OR = 4.048, CI = 2.678-6.119; p = 0.000, OR = 2.861, CI = 1.928-4.245).
      CONCLUSION: The present study shows that rs7217186:C > T and rs2619112:G > A of
      ALOX15 are associated with increased risk of CAD in the North Indian population.

PMID- 29068245
TI  - Sustainability of an early detection program for autism spectrum disorder over
      the course of 8 years.
AB  - The importance of early detection of autism spectrum disorder followed by early
      intervention is increasingly recognized. This quasi-experimental study evaluated
      the long-term effects of a program for the early detection of autism spectrum
      disorder (consisting of training of professionals and use of a referral protocol
      and screening instrument), to determine whether the positive effects on the age
      at referral were sustained after the program ended while controlling for overall
      changes in the number of referrals. Before, during, and after the program, the
      proportion of children referred before 3 years (versus 3-6 years) of age was
      calculated for children subsequently diagnosed with autism spectrum disorder ( N
      = 513) or another, non-autism spectrum disorder, condition ( N = 722). The odds
      of being referred before 3 years of age was higher in children with autism
      spectrum disorder than in children with another condition during the program than
      before (3.1, 95% confidence interval: 1.2-7.6) or after (1.7, 95% confidence
      interval: 1.0-3.0) the program but was not different before versus after the
      program. Thus, although the program led to earlier referral of children with
      autism spectrum disorder, after correction for other referrals, the effect was
      not sustained after the program ended. This study highlights the importance of
      continued investment in the early detection of autism spectrum disorder.

PMID- 29068243
TI  - Evidence for disruption of normal circadian cortisol rhythm in women with
      obesity.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in
      the pathogenesis of comorbidities encountered in obesity, including the relative
      hypogonadotropic hypogonadism that we and others have observed. We sought to
      examine serum cortisol profiles throughout the day and evening in a sample of
      normal weight women and women with obesity. In this cross-sectional study,
      regularly cycling obese (n = 12) and normal weight (n = 10) women were recruited.
      Mean serum cortisol was measured by frequent blood sampling for 16 h (8am
      midnight) in the luteal phase of the menstrual cycle. Women with obesity had
      significantly higher overall cortisol levels when compared to normal weight women
      (6.2 [4.3, 6.6] vs. 4.7 [3.7, 5.5] ug/dl, p = .04). Over the two-hour
      postprandial period, obese women displayed an almost two-fold greater (7.2 [6.5,
      8.6] ug/dl) rise in cortisol than normal weight controls (4.4 [3.7, 6.2] ug/dl, p
      < .01). In addition, obese women demonstrated a sustained evening cortisol
      elevation compared to normal weight women, who displayed the typical decline in
      cortisol (3.2 [2.3, 4] vs. 2 [1.5, 3.2] ug/dl, p < .05). Changes in the HPA axis
      in the setting of obesity may be related to risks of obesity-associated metabolic
      comorbidities and reproductive dysfunction often seen in these women.

PMID- 29068247
TI  - Australian elapid snake envenomation in cats: Clinical priorities and approach.
AB  - Practical relevance: No fewer than 140 species of terrestrial snakes reside in
      Australia, 92 of which possess venom glands. With the exception of the brown tree
      snake, the venom-producing snakes belong to the family Elapidae. The venom of a
      number of elapid species is more toxic than that of the Indian cobra and eastern
      diamondback rattle snake, which has earned Australia its reputation for being
      home to the world's most venomous snakes. Clinical challenges: The diagnosis of
      elapid snake envenomation is not always easy. Identification of Australian snakes
      is not straightforward and there are no pathognomonic clinical signs. In cats,
      diagnosis of envenomation is confounded by the fact that, in most cases, there is
      a delay in seeking veterinary attention, probably because snake encounters are
      not usually witnessed by owners, and also because of the tendency of cats to hide
      and seek seclusion when unwell. Although the administration of antivenom is
      associated with improved outcomes, the snake venom detection kit and antivenom
      are expensive and so their use may be precluded if there are financial
      constraints. Evidence base: In providing comprehensive guidance on the diagnosis
      and treatment of Australian elapid snake envenomation in cats, the authors of
      this review draw on the published veterinary, medical and toxicology literature,
      as well as their professional experience as specialists in medicine, and
      emergency medicine and critical care.

PMID- 29068246
TI  - Health Professionals Prefer to Communicate Risk-Related Numerical Information
      Using "1-in-X" Ratios.
AB  - BACKGROUND: Previous research has shown that format effects, such as the "1-in-X"
      effect-whereby "1-in-X" ratios lead to a higher perceived probability than "N-in
      N*X" ratios-alter perceptions of medical probabilities. We do not know, however,
      how prevalent this effect is in practice; i.e., how often health professionals
      use the "1-in-X" ratio. METHODS: We assembled 4 different sources of evidence,
      involving experimental work and corpus studies, to examine the use of "1-in-X"
      and other numerical formats quantifying probability. RESULTS: Our results
      revealed that the use of the "1-in-X" ratio is prevalent and that health
      professionals prefer this format compared with other numerical formats (i.e., the
      "N-in-N*X", %, and decimal formats). In Study 1, UK family physicians preferred
      to communicate prenatal risk using a "1-in-X" ratio (80.4%, n = 131) across
      different risk levels and regardless of patients' numeracy levels. In Study 2, a
      sample from the UK adult population ( n = 203) reported that most GPs (60.6%)
      preferred to use "1-in-X" ratios compared with other formats. In Study 3, "1-in
      X" ratios were the most commonly used format in a set of randomly sampled drug
      leaflets describing the risk of side effects (100%, n = 94). In Study 4, the "1
      in-X" format was the most commonly used numerical expression of medical
      probabilities or frequencies on the UK's NHS website (45.7%, n = 2,469
      sentences). CONCLUSIONS: The prevalent use of "1-in-X" ratios magnifies the
      chances of increased subjective probability. Further research should establish
      clinical significance of the "1-in-X" effect.

PMID- 29068249
TI  - News & Views.

PMID- 29068248
TI  - Diabetic ketoacidosis in the cat: Recognition and essential treatment.
AB  - : Practical relevance: Diabetic ketoacidosis (DKA) is a not uncommon emergency in
      both newly diagnosed and poorly regulated diabetic cats. When there is a
      heightened metabolic rate and energy requirement due to concurrent illness, an
      increase in the release of glucose counter-regulatory hormones causes insulin
      receptor resistance, lipolysis, free fatty acid release and ketogenesis. This
      necessitates not only treatment to eliminate the ketosis and control blood
      glucose, but also investigation of concurrent illnesses. Clinical challenges: A
      number of metabolic derangements can occur with DKA, requiring a comprehensive
      diagnostic evaluation, elimination of ketones, careful correction of glucose,
      electrolyte and acid base abnormalities, and close monitoring. AUDIENCE: Any
      veterinarian that cares for cats in urgent and emergency situations should
      understand the pathophysiology of DKA in order to address an individual's
      clinical signs and metabolic derangements. Evidence base: This review draws
      evidence from the peer-reviewed literature as well as the author's personal
      clinical experience.

PMID- 29068250
TI  - Australian and New Zealand College of Veterinary Scientists abstracts 2017.

PMID- 29068251
TI  - Skin as a marker of general feline health: Cutaneous manifestations of infectious
      disease.
AB  - : Practical relevance: Infectious disease in feline patients often presents a
      diagnostic challenge. This article reviews the most relevant viral, bacterial and
      protozoal diseases and their cutaneous manifestations. Many of the diseases
      discussed have overlapping presentations or may mimic more common noninfectious
      disease processes. The purpose of the article is to reinforce knowledge of common
      and uncommon infectious diseases, help practitioners identify possible infectious
      dermatoses, create a comprehensive and prioritized differential list, and provide
      guidance for the diagnosis of these diseases. A working knowledge of these
      clinical syndromes is important if what is thought to be a case of a common
      disease does not respond to conventional management. AUDIENCE: This review is
      aimed at veterinarians who treat cats and especially those with an interest in
      feline dermatology. Tables are included to allow the reader to formulate a
      concise list of differential diagnoses for clinically similar presentations. The
      diagnostic approach to a case of ulcerative facial dermatitis is reviewed in a
      Case Notes quiz. Evidence base: This article includes up-to-date information
      regarding dermatologic manifestations of less commonly encountered feline
      cutaneous infectious diseases. Information has been drawn from the published,
      peer-reviewed literature and the most recent textbook chapters with a particular
      aim of describing and differentiating clinical lesions and the diagnostic
      approach to cutaneous disease, especially in unusual cases.

PMID- 29068252
TI  - Pyrexia in cats: new data to inform clinical decision-making.

PMID- 29068253
TI  - Topical E6005/RVT-501, a novel phosphodiesterase 4 inhibitor, for the treatment
      of atopic dermatitis.
AB  - INTRODUCTION: Local adverse effects of steroid use and the burning sensation of
      calcineurin inhibitors impair patients' adherence to treatment and decrease the
      treatment response in atopic dermatitis (AD). Steroid phobia appears to be a
      psychological problem in patients with AD. Topical non-steroidal remedies are in
      demand. Areas covered: This manuscript reviews the current literature on
      preclinical and clinical studies regarding topical E6005/RVT-501, a novel
      phosphodiesterase 4 inhibitor. We also discuss the mechanistic background of
      E6005/RVT-501 in the treatment of AD. Expert opinion: Topical E6005/RVT-501
      improves skin eruption and pruritus of pediatric and adult AD patients without
      any serious side effects. It is useful for mild to moderate lesions of AD in
      pediatric and adult patients. Topical E6005/RVT-501 is non-steroidal agent but
      its potency is equal to that of mild rank topical steroid, therefore, it may fit
      the demand of patients with steroid phobia. Its steroid-sparing effects may also
      be investigated in future clinical trials and may minimize the dose and frequency
      of topical steroids.

PMID- 29068254
TI  - Assessment of clot length with multiphase CT angiography in patients with acute
      ischemic stroke.
AB  - Introduction Existing stroke literature demonstrates that rapid recanalization of
      vessels improves long-term prognosis after acute ischemic stroke. However,
      further optimization of the speed of the thrombectomy procedure, used to
      recanalize a blocked vessel, is limited by our minimal knowledge of the clot
      dimensions pre-procedure. Knowing the clot dimensions would allow planning of the
      thrombectomy procedure with the appropriate size and length of stent retriever,
      and determination of the correct site of the stent deployment ensuring total
      coverage of the clot by the stent retriever. Methods We performed a feasibility
      study to assess if multiphase computed tomography angiography (mCTA) can be used
      to estimate clot length by comparing CTA imaging data with imaging data obtained
      from conventional digital subtraction angiography (DSA). A retrospective chart
      review was performed of patients with clots in the proximal middle cerebral
      artery and adequate collateral circulation, who underwent both mCTA and DSA.
      Results Clot length was not significantly different on 3D mCTA versus mCTA MIPs,
      nor was it significantly different on MIP mCTA versus DSA. Pathological evidence
      also supported our ability to measure clot length on mCTA. Conclusions We suggest
      that mCTA is a reliable and valid measure of clot length in acute ischemic stroke
      patients.

PMID- 29068258
TI  - [Articles of the Hungarian Medical Journal from January, 1996].

PMID- 29068255
TI  - Burden of hospitalization in clinically diagnosed peripheral artery disease: A
      community-based study.
AB  - The burden and predictors of hospitalization over time in community-based
      patients with peripheral artery disease (PAD) have not been established. This
      study evaluates the frequency, reasons and predictors of hospitalization over
      time in community-based patients with PAD. We assembled an inception cohort of
      1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female)
      from 1 January 1998 through 31 December 2011 who were followed until 2014. Two
      age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9
      codes were used to ascertain the primary reasons for hospitalization. Patients
      were censored at death or last follow-up. The most frequent reasons for
      hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases
      and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and
      2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%)
      cases and 1588 (44%) controls ( p < 0.001) >= two times. In adjusted models, age,
      prior hospitalization and comorbid conditions were independently associated with
      increased risk of recurrent hospitalizations in both groups. In cases, severe PAD
      (ankle-brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly
      compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with
      increased risk for recurrent hospitalization. We demonstrate an increased rate of
      hospitalization in community-based patients with PAD and identify predictors of
      recurrent hospitalizations. These observations may inform strategies to reduce
      the burden of hospitalization of PAD patients.

PMID- 29068257
TI  - Definitive screening design enables optimization of LC-ESI-MS/MS parameters in
      proteomics.
AB  - In proteomics, more than 100,000 peptides are generated from the digestion of
      human cell lysates. Proteome samples have a broad dynamic range in protein
      abundance; therefore, it is critical to optimize various parameters of LC-ESI
      MS/MS to comprehensively identify these peptides. However, there are many
      parameters for LC-ESI-MS/MS analysis. In this study, we applied definitive
      screening design to simultaneously optimize 14 parameters in the operation of
      monolithic capillary LC-ESI-MS/MS to increase the number of identified proteins
      and/or the average peak area of MS1. The simultaneous optimization enabled the
      determination of two-factor interactions between LC and MS. Finally, we found two
      parameter sets of monolithic capillary LC-ESI-MS/MS that increased the number of
      identified proteins by 8.1% or the average peak area of MS1 by 67%. The
      definitive screening design would be highly useful for high-throughput analysis
      of the best parameter set in LC-ESI-MS/MS systems.

PMID- 29068259
TI  - [Articles of the Hungarian Medical Journal from February, 1996].

PMID- 29068260
TI  - [Articles of the Hungarian Medical Journal from September, 1996].

PMID- 29068256
TI  - Longitudinal evaluation of resting-state connectivity, white matter integrity and
      cortical thickness in stable HIV infection: Preliminary results.
AB  - Purpose The objectives of this study were to determine if HIV-infected patients
      treated with highly active antiretroviral therapy (HAART), without dementia,
      suffer from longitudinal gray matter (GM) volume loss, changes in white matter
      (WM) integrity and deterioration in functional connectivity at rest, in an
      average interval of 30 months. Methods Clinically stable HIV-positive patients
      (on HAART, CD4 + T lymphocyte > 200 cells/MUl, and viral loads <50 copies/MUl)
      were recruited. None of them had HIV-associated dementia. Each patient underwent
      two scans, performed in a 1.5-T magnetic resonance imaging (MRI) scanner.
      FreeSurfer was used to perform cortical volumetric reconstruction and
      segmentation of GM structures. WM integrity was assessed using tract-based
      spatial statistics to post-process diffusion tensor imaging data, and FMRIB's
      Software Library tools were used to post-process resting-state functional
      magnetic resonance imaging (RS-fMRI). Results There were no significant
      differences in cortical thickness, deep GM volumes, or diffusivity parameters
      between the scans at the two time points. Five resting-state networks were
      identified in our patients. In the second MRI, HIV-positive patients presented
      increased areas of functional connectivity in visual pathways, frontoparietal and
      cerebellar networks, compared with the first MRI (considering p < 0.05).
      Conclusions RS-fMRI revealed potentially compensatory longitudinal alterations in
      the brains of HIV-positive patients, attempting to compensate for brain damage
      related to the infection.

PMID- 29068261
TI  - Health Information Infrastructure for People with Intellectual and Developmental
      Disabilities (I/DD) Living in Supported Accommodation: Communication, Co
      Ordination and Integration of Health Information.
AB  - People with intellectual and/or developmental disability (I/DD) commonly have
      complex health care needs, but little is known about how their health information
      is managed in supported accommodation, and across health services providers. This
      study aimed to describe the current health information infrastructure (i.e., how
      data and information are collected, stored, communicated, and used) for people
      with I/DD living in supported accommodation in Australia. It involved a scoping
      review and synthesis of research, policies, and health documents relevant in this
      setting. Iterative database and hand searches were conducted across peer-reviewed
      articles internationally in English and grey literature in Australia (New South
      Wales) up to September 2015. Data were extracted from the selected relevant
      literature and analyzed for content themes. Expert stakeholders were consulted to
      verify the authors' interpretations of the information and content categories.
      The included 286 sources (peer-reviewed n = 27; grey literature n = 259) reflect
      that the health information for people with I/DD in supported accommodation is
      poorly communicated, coordinated and integrated across isolated systems. 'Work-as
      imagined' as outlined in policies, does not align with 'work-as-done' in reality.
      This gap threatens the quality of care and safety of people with I/DD in these
      settings. The effectiveness of the health information infrastructure and services
      for people with I/DD can be improved by integrating the information sources and
      placing people with I/DD and their supporters at the centre of the information
      exchange process.

PMID- 29068262
TI  - Correction to: Zhang et al., Quantification of manganese and mercury in toenail
      in vivo using portable X-ray fluorescence (XRF).

PMID- 29068263
TI  - Hydric "Costs" of Reproduction: Pregnancy Increases Evaporative Water Loss in the
      Snake Vipera aspis.
AB  - Water constraints can mediate evolutionary conflict either among individuals
      (e.g., parent-offspring conflict, sexual conflict) or within an individual (e.g.,
      cost of reproduction). During pregnancy, water is of particular importance
      because the female provides all water needed for embryonic development and
      experiences important maternal shifts in behavior and physiology that, together,
      can compromise female water balance if water availability is limited. We examined
      the effect of pregnancy on evaporative water loss and microhabitat selection in a
      viviparous snake, the aspic viper. We found that both physiological (increased
      metabolism and body temperature) and morphological (body distension) changes
      contribute to an increased evaporative water loss in pregnant females. We also
      found that pregnant females in the wild select warmer and moister basking
      locations than nonreproductive females, likely to mitigate the conflict between
      thermal needs and water loss. Water resources likely induce significant
      reproductive constraints across diverse taxa and thus warrant further
      consideration in ecological research. From an evolutionary perspective, water
      constraints during reproduction may contribute to shaping reproductive effort.

PMID- 29068264
TI  - Two consecutive successful live birth in woman with 17alpha hydroxylase
      deficiency by frozen-thaw embryo transfer under hormone replacement endometrium
      preparation.
AB  - 17alpha-Hydroxylase deficiency is rare autosomal recessive disorder that
      manifested by hypertension, hypokalemia, delayed sexual development, primary
      amenorrhea and infertility. The information regarding infertility care and
      conception in women with this disorder are extremely limited. We report a 24-year
      old Japanese woman with primary amenorrhea who was diagnosed as partial 17alpha
      hydroxylase deficiency caused by homozygous 3 bp deletion in exon 1 of 17alpha
      hydroxylase gene. In vitro fertilization with controlled ovarian stimulation was
      carried out and all viable embryo were frozen. During ovarian stimulation, serum
      progesterone levels were markedly elevated, and endometrial growth was impaired.
      Utilizing frozen-thaw embryo transfer under hormonal replacement (glucocorticoid,
      estradiol and progesterone), she had successfully given two consecutive live
      birth. Women with 17alpha-hydroxylase deficiency with residual ovarian reserve
      can afford reproductive success by appropriate diagnosis and treatment by
      assisted reproductive technology.

PMID- 29068265
TI  - Effects of different percentages of body weight support on spatiotemporal step
      characteristics during running.
AB  - This study aimed to determine the effect of different percentages of body weight
      support (BWS) on spatiotemporal step characteristics during running. 26 endurance
      runners (age: 37 +/- 9 years) completed a running treadmill protocol consisting
      of 6 different conditions (BWS combinations: 0-50%), with velocity maintained at
      12 km/h. Each condition lasted 1 minute. Step angle, ground contact time (CT),
      flight time (FT), step length (SL) and frequency (SF), and duration of phases
      during stance time (phase1: initial contact; phase2: midstance; phase3:
      propulsion) were measured for every step during the test using a photoelectric
      cell system. Compared with the baseline condition (100% BW), FT was longer, CT
      was shorter, SL was longer, SF was lower, and the step angle was higher with each
      increase in BWS (p < 0.05). Also, some changes were observed in the duration of
      phases during stance time: phase1 did not experience changes across experimental
      conditions (p = 0.096), phase2 decreased and phase3 increased as BW was supported
      (p < 0.05). These results indicate that as BW was supported, runners showed
      longer FT and SL, shorter CT, lower SF, and greater step angle as well as some
      changes in the phases during the ground contact. Therefore, this study highlights
      the effect of different percentages of BWS on spatiotemporal parameters.

PMID- 29068266
TI  - Individually tailored internet-based cognitive behaviour therapy for older adults
      with anxiety and depression: a randomised controlled trial.
AB  - Mixed anxiety and depression is common among older adults. The aim of the study
      was to compare the effects of an eight-week-long tailored internet-supported
      cognitive behaviour therapy (ICBT) programme and to compare against the provision
      of weekly general support. A second aim was to investigate if pre-treatment
      cognitive flexibility and self-reported cognitive problems would predict outcome.
      We included 66 older adults (aged over 60 years) with mixed anxiety/depression
      following media recruitment and randomised them into treatment and control
      groups. We also included a one-year follow-up. As a measure of executive
      function, we used the Wisconsin Card Sorting Test (perseverative errors) and the
      Cognitive Failures Questionnaire during the pre-treatment phase. Results showed a
      moderate between-group effect on the main outcome measure, the Beck Anxiety
      Inventory (BAI) (d= .50), favouring the treatment group. Nearly half (45.5%) of
      that group were classified as responders. One person (3%) in the treatment group
      deteriorated. There were significant correlations between perseverative errors
      and outcome (on the BAI r = -.45), but not among self-reported cognitive
      function. We conclude that guided, tailored ICBT may be effective for some older
      adults and that the role of cognitive function needs to be investigated further.

PMID- 29068267
TI  - Speech outcome in young children born with unilateral cleft lip and palate
      treated with one- or two-stage palatal repair and the impact of early
      intervention.
AB  - OBJECTIVES: The aim of this study was to describe speech at 1, 1;6 and 3 years of
      age in children born with unilateral cleft lip and palate (UCLP) and relate the
      findings to operation method and amount of early intervention received. METHODS:
      A prospective trial of children born with UCLP operated with a one-stage (OS)
      palatal repair at 12 months or a two-stage repair (TS) with soft palate closure
      at 3-4 months and hard palate closure at 12 months was undertaken (Scandcleft).
      At 1 and 1;6 years the place and manner of articulation and number of different
      consonants produced in babbling were reported in 33 children. At three years of
      age percentage consonants correct adjusted for age (PCC-A) and cleft speech
      errors were assessed in 26 of the 33 children. Early intervention was not
      provided as part of the trial but according to the clinical routine and was
      extracted from patient records. RESULTS: At age 3, the mean PCC-A was 68% and 46%
      of the children produced articulation errors with no significant difference
      between the two groups. At one year there was a significantly higher occurrence
      of oral stops and anterior place consonants in the TS group. There were
      significant correlations between the consonant production between one and three
      years of age, but not with amount of early intervention received. CONCLUSIONS:
      The TS method was beneficial for consonant production at age 1, but not shown at
      1;6 or 3 years. Behaviourally based early intervention still needs to be
      evaluated.

PMID- 29068268
TI  - Structural insights into the binding mode of flavonols with the active site of
      matrix metalloproteinase-9 through molecular docking and molecular dynamic
      simulations studies.
AB  - Cartilage degradation in rheumatoid arthritis is mediated principally by the
      collagenases and gelatinases. Gelatinase B (also called matrix metalloproteinase
      9 - MMP-9), is a valid target molecule which is known to participate in cartilage
      degradation as well as angiogenesis associated with the disease and inhibition of
      its activity shall prevent cartilage damage and angiogenesis. The focus of this
      study is to investigate the possibilities of MMP-9 inhibition by flavonol class
      of bioflavonoids by studying their crucial binding interactions at the active
      site of MMP 9 using molecular docking (Glide XP and QPLD) and further
      improvisation by post-docking MM-GBSA and molecular dynamic (MD) simulations. The
      results show that flavonols can convincingly bind to active site of MMP-9 as
      demonstrated by their stable interactions at the S1' specificity pocket and
      favourable binding energies. Gossypin has emerged as a promising candidate with a
      docking score of -14.618 kcal/mol, binding energy of -79.97 kcal/mol and a stable
      MD pattern over 15 ns. In addition, interaction mechanisms with respect to
      catalytic site zinc are also discussed. Further, the drug-like characters of the
      ligands were also analysed using ADME analysis.

PMID- 29068270
TI  - President's message: Deliberate epidemics.

PMID- 29068269
TI  - Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and
      Meta-Analysis.
AB  - RATIONALE: The application of prone positioning for acute respiratory distress
      syndrome (ARDS) has evolved, with recent trials focusing on patients with more
      severe ARDS, and applying prone ventilation for more prolonged periods.
      OBJECTIVES: This review evaluates the effect of prone positioning on 28-day
      mortality (primary outcome) compared with conventional mechanical ventilation in
      the supine position for adults with ARDS. METHODS: We updated the literature
      search from a systematic review published in 2010, searching MEDLINE, EMBASE, and
      CENTRAL (through to August 2016). We included randomized, controlled trials
      (RCTs) comparing prone to supine positioning in mechanically ventilated adults
      with ARDS, and conducted sensitivity analyses to explore the effects of duration
      of prone ventilation, concurrent lung-protective ventilation and ARDS severity.
      Secondary outcomes included PaO2/FiO2 ratio on Day 4 and an evaluation of adverse
      events. Meta-analyses used random effects models. Methodologic quality of the
      RCTs was evaluated using the Cochrane risk of bias instrument, and methodologic
      quality of the overall body of evidence was evaluated using the GRADE (Grading of
      Recommendations Assessment, Development, and Evaluation) guidelines. RESULTS:
      Eight RCTs fulfilled entry criteria, and included 2,129 patients (1,093 [51%]
      proned). Meta-analysis revealed no difference in mortality (risk ratio [RR],
      0.84; 95% confidence interval [CI], 0.68-1.04), but subgroup analyses found lower
      mortality with 12 hours or greater duration prone (five trials; RR, 0.74; 95% CI,
      0.56-0.99) and for patients with moderate to severe ARDS (five trials; RR, 0.74;
      95% CI, 0.56-0.99). PaO2/FiO2 ratio on Day 4 for all patients was significantly
      higher in the prone positioning group (mean difference, 23.5; 95% CI, 12.4-34.5).
      Prone positioning was associated with higher rates of endotracheal tube
      obstruction and pressure sores. Risk of bias was low across the trials.
      CONCLUSIONS: Prone positioning is likely to reduce mortality among patients with
      severe ARDS when applied for at least 12 hours daily.

PMID- 29068272
TI  - Nocardioides immobilis sp. nov., isolated from iron mine soil.
AB  - A Gram-positive, non-motile, rod-shaped aerobic bacterial strain FLL521T was
      isolated from iron mine soil. Phylogenetic trees based on 16S rRNA gene sequences
      showed that strain FLL521T belonged to genus Nocardioides in family
      Nocardioidaceae, with the highest sequence identity to Nocardioides panacisoli
      GSoil 346T (96.3 %). The DNA G+C content of strain FLL521T was 70.3 mol%. The
      cell-wall peptidoglycan type was ll-2,6-diaminopimelic acid. The major
      respiratory quinone was MK-8(H4), and the predominant fatty acids (>5 %) were iso
      C16 : 0, C18 : 1omega9c and C17 : 1omega8c. The polar lipids of strain FLL521T
      were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol and three
      unidentified phospholipids. Strain FLL521T showed physiological and biochemical
      differences with the related strains in the Voges-Proskauer test, hydrolysis of l
      arginine, utilization of d-mannose, inositol, phenylalanine and acid production
      from l-arabinose. Based on the phenotypic, genotypic and phylogenetic analyses,
      strain FLL521T represents a novel species of Nocardioides, for which the name
      Nocardioides immobilis sp. nov. is proposed. The type strain is FLL521T (=KCTC
      39931T=CCTCC AB 2017083T).

PMID- 29068273
TI  - CD59 association with infectious bronchitis virus particles protects against
      antibody-dependent complement-mediated lysis.
AB  - CD59 protein functions as a negative regulator of the terminal pathway of the
      complement system by binding to the C8/C9 factors. To date, little is known about
      the role of CD59 in coronavirus infectious bronchitis virus (IBV) infection. In
      this study, we discovered that CD59 was downregulated in IBV-infected cells and
      was associated with IBV virions. This association protected IBV particles from
      antibody-dependent complement-mediated lysis. IBV titres in the supernatant were
      significantly increased when CD59 proteins were overexpressed in cells followed
      by IBV infection, and this observation was further supported by knockdown or
      cleavage of CD59. Because no considerable change in IBV N protein and viral RNA
      levels was detected in total cell lysates prepared from the overexpression,
      knockdown or cleavage of CD59 groups, our data indicated that CD59 was involved
      in IBV particle release and that IBV had evolved a mechanism to utilize CD59 to
      evade complement-mediated destruction.

PMID- 29068274
TI  - Colwellia beringensis sp. nov., a psychrophilic bacterium isolated from the
      Bering Sea.
AB  - A Gram stain-negative, motile and rod-shaped bacterial strain, designated NB097
      1T, was isolated from a marine sediment sample collected from the Bering Sea, and
      subjected to a polyphasic taxonomic study. Strain NB097-1T grew at 0-25  degrees
      C, with an optimum growth temperature of 10-13  degrees C. Phylogenetic trees
      reconstructed based on 16S rRNA gene sequences indicated that strain NB097-1T
      belonged to the genus Colwellia. Strain NB097-1T exhibited 16S rRNA gene sequence
      similarities of 98.6, 98.5, 98.0, 97.2 and 96.8 % with the type strains of
      Colwellia mytili, C. sediminilitoris, C. aestuarii, C. polaris and C.
      chukchiensis, respectively. Strain NB097-1T had Q-8 as the major respiratory
      quinone and contained summed feature 3 (C16 : 1omega7c and/or C16 : 1omega6c) and
      C16 : 0 as the major fatty acids. The major polar lipids detected in strain NB097
      1T were phosphatidylglycerol and phosphatidylethanolamine. The genomic DNA G+C
      content of strain NB097-1T was 38.5 mol%, and its average nucleotide identity
      values with the type strains of C. mytili, C. sediminilitoris, C. aestuarii, C.
      polaris and C. chukchiensis were 77.30, 78.99, 78.82, 80.66 and 75.77 %,
      respectively. On the basis of phenotypic, chemotaxonomic and phylogenetic
      properties, together with average nucleotide identity value data, strain NB097-1T
      represents a novel species of the genus Colwellia, for which the name Colwellia
      beringensis sp. nov. is proposed. The type strain is NB097-1T (=MCCC
      1A11668T=KCTC 52554T).

PMID- 29068275
TI  - Investigation of next-generation sequencing data of Klebsiella pneumoniae using
      web-based tools.
AB  - PURPOSE: Rapid identification and characterization of multidrug-resistant
      Klebsiella pneumoniae strains is necessary due to the increasing frequency of
      severe infections in patients. The decreasing cost of next-generation sequencing
      enables us to obtain a comprehensive overview of genetic information in one step.
      The aim of this study is to demonstrate and evaluate the utility and scope of the
      application of web-based databases to next-generation sequenced (NGS) data.
      METHODOLOGY: The whole genomes of 11 clinical Klebsiella pneumoniae isolates were
      sequenced using Illumina MiSeq. Selected web-based tools were used to identify a
      variety of genetic characteristics, such as acquired antimicrobial resistance
      genes, multilocus sequence types, plasmid replicons, and identify virulence
      factors, such as virulence genes, cps clusters, urease-nickel clusters and efflux
      systems. RESULTS: Using web-based tools hosted by the Center for Genomic
      Epidemiology, we detected resistance to 8 main antimicrobial groups with at least
      11 acquired resistance genes. The isolates were divided into eight sequence types
      (ST11, 23, 37, 323, 433, 495 and 562, and a new one, ST1646). All of the isolates
      carried replicons of large plasmids. Capsular types, virulence factors and genes
      coding AcrAB and OqxAB efflux pumps were detected using BIGSdb-Kp, whereas the
      selected virulence genes, identified in almost all of the isolates, were detected
      using CLC Genomic Workbench software. CONCLUSION: Applying appropriate web-based
      online tools to NGS data enables the rapid extraction of comprehensive
      information that can be used for more efficient diagnosis and treatment of
      patients, while data processing is free of charge, easy and time-efficient.

PMID- 29068277
TI  - Paenibacillus crassostreae sp. nov., isolated from the Pacific oyster Crassostrea
      gigas.
AB  - A Gram-stain-positive, endospore-forming, rod-shaped, aerobic bacterium,
      designated LPB0068T, was isolated from a Pacific oyster (Crassostrea gigas) in
      Korea. This isolate was found to share the highest 16S rRNA gene sequence
      similarity with Paenibacillus macquariensis subsp. macquariensis DSM 2T (98.1 %)
      and Paenibacillus macquariensis subsp. defensor JCM 14954T (98.0 %). To establish
      the genomic relatedness of this isolate to its phylogenetic neighbours, its
      genome sequence and those of Paenibacillus antarcticus CECT 5836T, P.
      macquariensis subsp. macquariensis DSM 2T, P. macquariensis subsp. defensor JCM
      14954T, and Paenibacillus glacialis DSM 22343T were determined. The low average
      nucleotide identity and digital DNA-DNA hybridization values exhibited by
      LPB0068T in relation to the other strains in this analysis revealed that it is
      distinct from other Paenibacillus species. The genome of strain LPB0068T consists
      of one chromosome and three circular plasmids, and had a DNA G+C content of 40.0
      mol%. The major respiratory quinone was menaquinone-7 and the diagnostic diamino
      acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major polar
      lipids consisted of phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylethanolamine, one unidentified phospholipid, one unidentified
      glycolipid, and two unidentified polar lipids. The major cellular fatty acids
      were anteiso-C15 : 0, C14 : 0, and C16 : 0. Based on genomic, phylogenetic, and
      phenotypic characteristics, this strain was clearly distinguished from other
      Paenibacillus species with validly published names and should therefore be
      classified as a novel species of the genus. The name Paenibacillus crassostreae
      sp. nov. is proposed, the type strain of which is LPB0068T (=KACC 18694T=JCM
      31183T).

PMID- 29068278
TI  - An investigation of antifungal stewardship programmes in England.
AB  - PURPOSE: We sought to explore the current status of antifungal stewardship (AFS)
      initiatives across National Health Service (NHS) Trusts within England, the
      challenges and barriers, as well as ways to improve current AFS programmes.
      METHODOLOGY: An electronic survey was sent to all 155 acute NHS Trusts in
      England. A total of 47 Trusts, corresponding to 30 % of English acute Trusts,
      responded to the the survey; 46 Trusts (98 %) had an antimicrobial stewardship
      (AMS) programme but only 5 (11 %) had a dedicated AFS programme. Overall, 20 (43
      %) Trusts said they included AFS as part of their AMS programmes. From those
      conducting AFS programmes, 7 (28 %) have an AFS/management team, 16 (64 %)
      monitor and report on antifungal usage, 5 (20 %) have dedicated AFS ward rounds
      and 12 (48 %) are directly involved in the management of invasive fungal
      infections.Results/Key findings. Altogether, 13 acute Trusts (52 %) started their
      AFS programme to manage costs, whilst 12 (48 %) commenced the programme due to
      clinical need; 27 (73 %) declared that they would increase their AFS initiatives
      if they could. Of those without an AFS programme, 14 (67 %) responded that this
      was due to lack of resources/staff time. Overall, 12 Trusts (57 %) responded that
      the availability of rapid diagnostics and clinical support would enable them to
      conduct AFS activities. CONCLUSION: Although a minority of Trusts conduct
      dedicated AFS programmes, nearly half include AFS as part of routine AMS
      activities. Cost issues are the main driver for AFS, followed by clinical need.
      The availability of rapid diagnostics and clinical support could help increase
      AFS initiatives.

PMID- 29068276
TI  - Reclassification of a Polynucleobacter cosmopolitanus strain isolated from
      tropical Lake Victoria as Polynucleobacter victoriensis sp. nov.
AB  - The genus Polynucleobacter (family Burkholderiaceae) is phylogenetically
      subdivided into at least four subclusters. One of those, subcluster PnecC, was
      recognized as a cryptic species complex. Here we test by comparative genome
      analyses whether subcluster PnecD, currently solely represented by the species
      Polynucleobactercosmopolitanus, also represents such a cryptic species complex.
      The genome sequences of the two P. cosmopolitanus strains, MWH-MoIso2T and MWH
      VicM1, were determined. The latter strain was also characterized in the previous
      description of P. cosmopolitanus. These two strains originate from a temperate
      lake located in Austria and from the large tropical Lake Victoria located in East
      Africa, respectively. Strains MWH-MoIso2T and MWH-VicM1 possess quite small
      genomes of 1.78 and 1.63 Mbp, respectively, and share similar G+C values of 44.1
      and 43.1 mol%, respectively. Both strains encode only a single copy of the
      ribosomal operon, and their 16S rRNA genes differ only in four positions,
      equalling a sequence similarity of 99.74 %. Both genomes possess characteristics
      indicating evolutionary genome streamlining, such as high coding densities of
      93.9 and 94.6 % of bases, respectively. Average nucleotide identity (ANI)
      comparisons of the genomes of the two strains resulted in a value of 78.4 %,
      suggesting that each of the strains represents a separate species. Our
      investigation suggests that PnecD represents an additional cryptic species
      complex within the genus Polynucleobacter that was not resolved by 16S rRNA gene
      sequence analyses. We propose reclassification of strain MWH-VicM1 as
      Polynucleobacter victoriensis sp. nov., with type strain MWH-VicM1T(=DSM
      21486T=JCM 32005T).

PMID- 29068280
TI  - Prevalence of respiratory viruses in Iranian patients with idiopathic pulmonary
      fibrosis.
AB  - INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately
      fatal lung disease. One of the risk factors involved in the acquisition of IPF is
      viral infections, especially respiratory viruses. In the present study, we
      investigated the detection of respiratory viruses and the possible relationship
      between these viruses and IPF. METHODS: This cross-sectional study was supported
      by the Iran University of Medical Sciences (IUMS), Tehran, Iran. A total of 40
      respiratory samples (five nasopharyngeal and 35 bronchoalveolar lavage specimens)
      were obtained from IPF patients referred to IUMS hospitals between April 2015 and
      December 2016. Assays were performed using the CLART Pneumovir DNA array assay,
      which made it possible to detect five genera of respiratory viruses
      simultaneously.Results/Key findings. Altogether, 22 of the 40 participants were
      male. Respiratory syncytial virus (RSV), parainfluenza, rhino, corona and
      influenza viruses were found in 2.5 % (1/40), 7.5 % (3/40), 10 % (4/40), 2.5 %
      (1/40) and 0% (0/40) of cases, respectively. CONCLUSION: Determining a
      correlation between the viruses and IPF is not an easy task, and therefore, this
      will require more research. In addition, the CLART Pneumovir DNA array can be
      considered as a useful method for simultaneous detection of several viral
      respiratory infections.

PMID- 29068281
TI  - Detection of Bartonella in cat scratch disease using a single-step PCR assay kit.
AB  - PURPOSE: Bartonella is an increasingly isolated emerging pathogen that can cause
      severe illness in humans, including cat scratch disease (CSD). The bacteria are
      difficult to grow and thus many detection methods have been developed, especially
      molecular. We previously developed a PCR method targeting ribC to identify
      Bartonella sp. A manufactured kit (RealCycler BART, Progenie Molecular) was
      commercialised shortly thereafter for the detection of Bartonella infection,
      including Bartonella henselae. METHODOLOGY: We performed a comparison between
      this test and our in-house PCR assay on 73 lymphadenopathy samples sent to the
      laboratory for suspicion of CSD.Results/Key findings. Among the 28 positive
      samples for Bartonella, 21 were identified by the two PCR assays, and seven by
      the commercial kit only. CONCLUSION: The performance of this commercial kit
      suggests that it could be a suitable alternative to our in-house PCR assay,
      highlighting the importance of the molecular methods used to diagnose CSD.

PMID- 29068279
TI  - Changchengzhania lutea gen. nov., sp. nov., a new member of the family
      Flavobacteriaceae isolated from Antarctic intertidal sediment.
AB  - A Gram-negative, aerobic, yellow pigmented, non-flagellated, non-gliding, rod
      shaped bacterial strain, designated SM1355T, was isolated from Antarctic
      intertidal sediment collected near the Chinese Antarctic Great Wall Station. The
      strain grew at 4-35  degrees C and with 0.5-7.0 % (w/v) NaCl. It hydrolysed
      aesculin but didn't reduce nitrate to nitrite. Phylogenetic analysis based on 16S
      rRNA gene sequences revealed that strain SM1355T formed a distinct phylogenetic
      lineage within the family Flavobacteriaceae, sharing the highest 16S rRNA gene
      sequence similarity with Flaviramulus ichthyoenteri (96.3 %) and fairly high
      sequence similarities (95.0-96.0 %) with over 20 recognized species in eight
      genera of the family Flavobacteriaceae. The predominant fatty acids were anteiso
      C15 : 0, iso-C15 : 0 and iso-C15 : 1 G. The major polar lipids were
      phosphatidylethanolamine and one unidentified lipid. The genomic DNA G+C content
      of strain SM1355T was 36.2 mol%. Based on the results of the polyphasic
      characterization for strain SM1355T, it is identified as the representative of a
      novel species in a new genus of the family Flavobacteriaceae, for which the name
      Changchengzhania lutea gen. nov., sp. nov. is proposed. The type strain of
      Changchengzhania lutea is SM1355T (=JCM 30336T=CCTCC AB 2014246T).

PMID- 29068283
TI  - Genomic diversity of human adenovirus type 3 isolated in Fukui, Japan over a 24
      year period.
AB  - Recently, human adenovirus type 3 (HAdV-3) has become the most isolated HAdV
      worldwide. Restriction endonuclease analysis of globally isolated strains of HAdV
      3 has uncovered 51 genome types to date. Information on the genome type is
      important to the epidemiological study of HAdV-3. In this study, analysis of 75
      isolates of HAdV- 3 collected over a 24-year period in Fukui revealed: (1) the
      emergence of three novel genome types (HAdV-3a52, HAdV-3a53 and HAdV-3a54) and
      two known genome types (HAdV-3a and HAdV-3a54); (2) the spectrum of diseases
      caused by individual genome types and their major involvement in the paediatric
      age population; and (3) the co-circulation and replacement of genome types as a
      usual phenomenon. The rising number of HAdV-3 genome types indicates that the
      genetic variation of HAdV-3 is more than other HAdVs. Considering the clinical
      importance of HAdV-3 infection, its genetic diversity underscores the need for
      its continuous surveillance and genetic characterization.

PMID- 29068282
TI  - Gordonia phthalatica sp. nov., a di-n-butyl phthalate-degrading bacterium
      isolated from activated sludge.
AB  - A phthalate esters-degrading bacterial strain, designated QH-11T, was isolated
      from an activated sludge wastewater treatment plant in Beijing, PR China. The
      cells were aerobic, Gram-stain-positive, non-motile, catalase-positive, oxidase
      negative, short rods and formed white colonies on trypticase soy agar. This
      isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and
      whole-cell hydrolysates contained arabinose and ribose. Diphosphatidylglycerol
      and phosphatidylethanolamine were the predominant polar lipids. According to the
      results of full-length of 16S rRNA gene sequence analysis, QH-11T represented a
      member of the genus Gordonia and showed the highest sequence similarity to
      Gordonia hydrophobica DSM 44015T (99.2 %), but was distinguishable by a low level
      of DNA-DNA relatedness (37.8 %). Genome-based comparisons indicated a clear
      distinction from the top ten most similar type strains (16S rRNA gene sequence)
      with pairwise average nucleotide identities (ANI) between 74.6 and 83.4 %. The
      predominant respiratory quinone was MK-9(H2), the mycolic acids present had 56 to
      62 carbon atoms, and the major fatty acids were C16 : 0 (33.3 %), C17 : 1omega8c
      (23.4 %) and C18 : 1omega9c (17.9 %). The DNA G+C content was 68.0 mol%. On the
      basis of the results of DNA-DNA hybridization, ANI and physiological and
      biochemical tests, it is proposed that QH-11T represents a novel species of the
      genus Gordonia, for which the name Gordonia phthalatica sp. nov. is proposed. The
      type strain is QH-11T (CICC 24107T =KCTC 39933T).

PMID- 29068285
TI  - Pectobacterium polaris sp. nov., isolated from potato (Solanum tuberosum).
AB  - The genus Pectobacterium, which belongs to the bacterial family
      Enterobacteriaceae, contains numerous species that cause soft rot diseases in a
      wide range of plants. The species Pectobacterium carotovorum is highly
      heterogeneous, indicating a need for re-evaluation and a better classification of
      the species. PacBio was used for sequencing of two soft-rot-causing bacterial
      strains (NIBIO1006T and NIBIO1392), initially identified as P. carotovorumstrains
      by fatty acid analysis and sequencing of three housekeeping genes (dnaX, icdA and
      mdh). Their taxonomic relationship to other Pectobacterium species was determined
      and the distance from any described species within the genus Pectobacterium was
      less than 94 % average nucleotide identity (ANI). Based on ANI, phylogenetic data
      and genome-to-genome distance, strains NIBIO1006T, NIBIO1392 and NCPPB3395 are
      suggested to represent a novel species of the genus Pectobacterium, for which the
      name Pectobacterium polaris sp. nov. is proposed. The type strain is NIBIO1006T
      (=DSM 105255T=NCPPB 4611T).

PMID- 29068284
TI  - The Agrobacterium tumefaciens CheY-like protein ClaR regulates biofilm formation.
AB  - The switch from a motile, planktonic existence to an attached biofilm is a major
      bacterial lifestyle transition that is often mediated by complex regulatory
      pathways. In this report, we describe a CheY-like protein required for control of
      the motile-to-sessile switch in the plant pathogen Agrobacterium tumefaciens.
      This regulator, which we have designated ClaR, possesses two distinct CheY-like
      receiver (REC) domains and is involved in the negative regulation of biofilm
      formation, through production of the unipolar polysaccharide (UPP) adhesin and
      cellulose. The ClaR REC domains share predicted structural homology with
      characterized REC domains and contain the majority of active site residues known
      to be essential for protein phosphorylation. REC1 is missing the conserved
      aspartate (N72) residue and although present in REC 2 (D193), it is not required
      for ClaR-dependent regulation suggesting that phosphorylation, which modulates
      the activity of many CheY-like proteins, appears not to be essential for ClaR
      activity. We also show that ClaR-dependent negative regulation of attachment is
      diminished significantly in mutants for PruA and PruR, proteins known to be
      involved in a pterin-mediated attachment regulation pathway. In A. tumefaciens,
      pterins are required for control of the intracellular signal cyclic diguanylate
      monophosphate through the DcpA regulator, but our findings suggest that pterin
      dependent ClaR control of attachment can function independently from DcpA,
      including dampening of c-di-GMP levels. This report of a novel CheY-type biofilm
      regulator in A. tumefaciens thus also adds significant details to the role of
      pterin-mediated signalling.

PMID- 29068286
TI  - Dynamic HIV-1 genetic recombination and genotypic drug resistance among treatment
      experienced adults in northern Ghana.
AB  - PURPOSE: There have been hardly any reports on the human immunodeficiency virus
      type 1 (HIV-1) drug-resistance profile from northern Ghana since antiretroviral
      therapy (ART) was introduced over a decade ago. This study investigated
      prevailing HIV-1 subtypes and examined the occurrence of drug resistance in ART
      experienced patients in Tamale, the capital of the Northern Region of Ghana.
      METHODOLOGY: A cross-sectional study was carried out on HIV-infected adult
      patients receiving first-line ART. HIV viral load (VL) and CD4+ T-cell counts
      were measured. The pol gene sequences were analysed for genotypic resistance by
      an in-house HIV-1 drug-resistance test; the prevailing HIV-1 subtypes were
      analysed in detail.Results/Key findings. A total of 33 subjects were studied.
      Participants comprised 11 males (33.3 %) and 22 (66.7 %) females, with a median
      age of 34.5 years [interquartile range (IQR) 30.0-40.3]. The median duration on
      ART was 12 months (IQR 8.0-24). Of the 24 subjects successfully genotyped, 10
      (41.7 %) viruses possessed at least one mutation conferring resistance to
      nucleoside or non-nucleoside reverse-transcriptase inhibitors (NRTIs/NNRTIs). Two
      class drug resistance to NRTI and NNRTI was mostly detected (25 %, 6/24). The
      most frequent mutations were lamivudine-resistance M184V and efavirenz/nevirapine
      resistance K103N. HIV-1 subtype CRF02_AG was predominant (79.2 %). Other HIV-1
      subtypes detected were G (8.3 %), A3 (4.2 %) and importantly two (8.3 %) unique
      HIV-1 recombinant forms with CRF02_AG/A3 mosaic. CONCLUSION: HIV-1 shows high
      genetic diversity and on-going viral genetic recombination in the study region.
      Nearly 42 % of the patients studied harboured a drug-resistant virus. The study
      underscores the need for continued surveillance of HIV-1 subtype diversity; and
      of drug-resistance patterns to guide selection of second-line regimens in
      northern Ghana.

PMID- 29068287
TI  - Hepatitis B virus X protein suppresses all-trans retinoic acid-induced apoptosis
      in human hepatocytes by repressing p14 expression via DNA methylation.
AB  - All-trans retinoic acid (ATRA), the most biologically active metabolite of
      vitamin A, is known to activate p14 expression via promoter hypermethylation to
      induce p53-dependent apoptosis in human hepatocytes. In this study, we found that
      the oncogenic hepatitis B virus (HBV) X protein (HBx) of HBV, derived from both
      overexpression and 1.2-mer replicon systems, suppresses ATRA-induced apoptosis in
      p53-positive human hepatocytes. For this effect, HBx upregulated both protein and
      enzyme activity levels of DNA methyltransferase 1, 3a and 3b, in the presence of
      ATRA and thereby inhibited p14 expression via promoter hypermethylation,
      resulting in inactivation of the p14-mouse double minute 2 pathway and subsequent
      downregulation of p53 levels. As a result, HBx was able to impair the potential
      of ATRA to activate apoptosis-related molecules, including Bax, p53-upregulated
      modulator of apoptosis, caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In
      conclusion, the present study provides a new oncogenic action mechanism of HBx,
      namely by suppressing the anticancer potential of ATRA to induce p53-dependent
      apoptosis in HBV-infected hepatocytes.

PMID- 29068288
TI  - Timing of surgical intervention for developmental dysplasia of the hip: a
      randomised controlled trial (Hip 'Op).
AB  - BACKGROUND: Developmental dysplasia of the hip (DDH) is a very common congenital
      disorder, and late-presenting cases often require surgical treatment. Surgical
      reduction of the hip may be complicated by avascular necrosis (AVN), which occurs
      as a result of interruption to the femoral head blood supply during treatment and
      can result in long-term problems. Some surgeons delay surgical treatment until
      the ossific nucleus (ON) has developed, whereas others believe that the earlier
      the reduction is performed, the better the result. Currently there is no
      definitive evidence to support either strategy. OBJECTIVES: To determine, in
      children aged 12 weeks to 13 months, whether or not delayed surgical treatment of
      a congenitally dislocated hip reduces the incidence of AVN at 5 years of age. The
      main clinical outcome measures were incidence of AVN and the need for a secondary
      surgical procedure during 5 years' follow-up. In addition, to perform (1) a
      qualitative evaluation of the adopted strategy and (2) a health economic analysis
      based on NHS and societal costs. DESIGN: Phase III, unmasked, randomised
      controlled trial with qualitative and health economics analyses. Participants
      were randomised 1 : 1 to undergo either early or delayed surgery. SETTING:
      Paediatric orthopaedic surgical centres in the UK. PARTICIPANTS: Children aged 12
      weeks to 13 months with DDH, either newly diagnosed or following failed
      splintage, and who required surgery. We had a target recruitment of 636 children.
      INTERVENTIONS: Surgical reduction of the hip performed as per the timing
      allocated at randomisation. MAIN OUTCOME MEASURES: Primary outcome - incidence of
      AVN at 5 years of age (according to the Kalamchi and MacEwen classification).
      Secondary outcomes - need for secondary surgery, presence or absence of the ON at
      the time of primary treatment, quality of life for the main carer and child, and
      a health economics and qualitative analysis. RESULTS: The trial closed early
      after reaching < 5% of the recruitment target. Fourteen patients were randomised
      to early treatment and 15 to delayed treatment. Implementation of rescue
      strategies did not improve recruitment. No primary outcome data were collected,
      and no meaningful conclusions could be made from the small number of non
      qualitative secondary outcome data. The qualitative work generated rich data
      around three key themes: (1) access to, and experiences of, primary and secondary
      care; (2) the impact of surgery on family life; and (3) participants' experiences
      of being in the trial. LIMITATIONS: Overoptimistic estimates of numbers of
      eligible patients seen at recruiting centres during the planning of the trial, as
      well as an overestimation of the recruitment rate, may have also contributed to
      unrealistic expectations on achievable patient numbers. FUTURE WORK: There may be
      scope for investigation using routinely available data. CONCLUSIONS: Hip 'Op has
      highlighted the importance of accurate advance information on numbers of
      available eligible patients, as well as support from all participating
      investigators when conducting surgical research. Despite substantial consultation
      with parents of children in the planning stage, the level of non-participation
      experienced during recruitment was much higher than anticipated. The qualitative
      work has emphasised the need for appropriate advice and robust support for
      parents regarding the 'real-life' aspects of managing children with DDH. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN76958754. FUNDING: This project was
      funded by the National Institute for Health Research (NIHR) Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 21, No. 63. See the NIHR Journals Library website for further
      project information.

PMID- 29068289
TI  - Medical Malpractice Reform: A Fix for a Problem Long out of Fashion.
AB  - State tort reforms have all but relegated the malpractice crisis to the history
      books. But there's good news for those of you into all things retro: The House of
      Representatives just voted to fix the malpractice crisis by a 222-197 margin.

PMID- 29068291
TI  - Theresa Blanco Often Manages Beyond Molina's Benefits Package.
AB  - For instance, say something a patient needs is not covered by Medicaid or an ACA
      plan. Blanco helps members find what they need by working with Molina's Community
      Connectors (community health workers) who help connect members to local community
      and not-for-profit organizations.

PMID- 29068290
TI  - Otezla, Warts and All, Racks Up Sales and Eyes Blockbuster Status.
AB  - Otezla-the generic name is apremilast-also exploited a new mechanism of action as
      the first inhibitor of phosphodiesterase 4 (PDE4) that results in increased
      expression of both anti-inflammatory proteins and reduced expression of their pro
      inflammatory counterparts.

PMID- 29068292
TI  - Insurers Relax Rules, Help Members After Hurricanes Harvey, Irma.
AB  - Some health plans responded by making it easier to see an out-of-network doctor,
      get a new copy of an insurance card or replace prescriptions lost in the chaos.
      Insurers also set up telephone help lines and made it easier to get a referral to
      a specialist.

PMID- 29068293
TI  - Jailbreak: How To Ease the Life Sentence of Inflammatory Bowel Disease.
AB  - Cutting-edge programs are sparing young people from many of the most dire IBD
      complications, which often occur when they are in school or starting careers and
      families. Most Crohn's patients are diagnosed in their teens and 20s; ulcerative
      colitis is typically diagnosed when a patient is between 30 and 40 years old.

PMID- 29068294
TI  - Young Man Battles For His Life Against Rare Autoimmune Disease.
AB  - The author's nephew suffers from a rare form of familial hemophagocytic
      lymphohistiocytosis. His organs shut down and he's placed in a medically induced
      coma. Meanwhile, costs mount to $4.9 million, most of it paid by an employer
      sponsored health plan.

PMID- 29068295
TI  - Congress Puts 'Shadow' Pricing Of MS Drugs in the Spotlight.
AB  - Lawmakers asked seven companies to explain not only "skyrocketing prices," but a
      practice known as shadow pricing in which a drugmaker increases the price of an
      existing medicine to match the price hike or higher price set for a new drug
      launched by another company.

PMID- 29068296
TI  - Time to Lift the Curtain On PBM Wheeling and Dealing.
AB  - PBMs say their deals need to be kept private so they can drive a hard bargain
      with manufacturers. But employers, consumer groups, and legislators are calling
      for more PBM transparency. There's bipartisan support for legislation that would
      force more openness.

PMID- 29068297
TI  - Diabetes Care Management Teams Did Not Reduce Utilization When Compared With
      Traditional Care: A Randomized Cluster Trial.
AB  - PURPOSE: Health services research evaluates redesign models for primary care.
      Care management is one alternative. Evaluation includes resource utilization as a
      criterion. Compare the impact of care-manager teams on resource utilization. The
      comparison includes entire panes of patients and the subset of patients with
      diabetes.DESIGN: Randomized, prospective, cohort study comparing change in
      utilization rates between groups, pre- and post-intervention.METHODOLOGY: Ten
      primary care physician panels in a safety-net setting. Ten physicians were
      randomized to either a care-management approach (Group 1) or a traditional
      approach (Group 2). Care managers focused on diabetes and the cardiovascular
      cluster of diseases. Analysis compared rates of hospitalization, 30-day
      readmission, emergency room visits, and urgent care visits. Analysis compared
      baseline rates to annual rates after a yearlong run-in for entire panels and the
      subset of patients with diabetes. RESULTS: Resource utilization showed no
      statistically significant change between baseline and Year 3 (P=.79). Emergency
      room visits and hospital readmission increased for both groups (P=.90), while
      hospital admissions and urgent care visits decreased (P=.73). Similarly,
      utilization was not significantly different for patients with diabetes
      (P=.69).CONCLUSIONS: A care-management team approach failed to improve resource
      utilization rates by entire panels and the subset of diabetic patients compared
      to traditional care. This reinforces the need for further evidentiary support for
      the care-management model's hypothesis in the safety net.

PMID- 29068298
TI  - Novartis's Kymriah: Harnessing Immune System Comes With Worry About Reining in
      Costs.
AB  - FDA approval of the CAR T-cell therapy for leukemia could usher in an era of
      genetically engineered, individually tailored immunotherapies. But tap those
      brakes. Long-term results are in short supply-and there's that $475,000 price
      tag. Or is it a $750,000 price tag?

PMID- 29068299
TI  - The Health Insurance Conundrum: Crossing the Divide.
AB  - Population health management is built on the notion that prevention, early
      intervention, and proactive management of chronic disease can reduce the
      incidence rates of costly episodes. But so far the economics are not penciling
      out. The cost of innovation is outstripping the financial return on investment.

PMID- 29068300
TI  - Health Plans Can't Ignore The Customer Experience Any Longer.
AB  - With regulations limiting differentiation between products, health plans must
      rethink consumer experience to meet expectations of today's consumers, who seek
      convenience, quality, and speed from their health care organizations. Many plans
      understand they need to connect more effectively with their end customers, but
      technological, cultural, and other obstacles are in the way.

PMID- 29068301
TI  - To Dent Soaring Drug Costs, States Turn to 'Price-Gouging' Laws.
AB  - States are facing unsustainable health care costs, and prescription drugs for
      Medicaid beneficiaries and state employees are the reason. From 2009 to 2013, the
      consumer price index (CPI) for prescription drugs increased about 11% vs. 8% for
      the overall CPI.

PMID- 29068302
TI  - Regimen Change: Gilead's TAF Drugs Toppling TDFs in HIV Treatment.
AB  - Truvada is getting a new lease on life as a preventive agent. It is the only drug
      approved to prevent HIV infections, and Truvada is the key pharmaceutical
      component of pre-exposure prophylaxis, which is aimed at preventing, rather than
      treating, HIV infection and transmission.

PMID- 29068303
TI  - Three Turbulent Spots That Could Ground Value-Based Care.
AB  - Many of today's value-based care models trace their roots to the Institute for
      Healthcare Improvement's Triple Aim. Arguably, their sustainability may hinge on
      how true they stay to that trinity of improving population health, the patient
      experience, and per capita costs.

PMID- 29068304
TI  - Anthem's Geoffrey B. Crawford Wants To Fix Wellness Programs.
AB  - The 35-year-old medical director of the plan's office of medical policy and
      technology assessment has broad interests, but he's particularly keen on wellness
      because it "ties into the evidentiary component of my position-evaluating the
      scientific literature to support evidence-based medicine." His take: Rely less on
      active patient participation.

PMID- 29068305
TI  - Fee-for-Service Is Dead. Long Live Fee for Service?
AB  - The move to a value-based payment system was supposed to end perverse incentives
      that pay doctors more for delivering often unnecessary services. But things are
      changing slowly and the market is still 95% fee for service. There's talk of
      reworking the Medicare fee schedule so docs are paid more for the things that
      work, and less for those that don't.

PMID- 29068306
TI  - Direct Primary Care Is About To Take Off - Or Maybe Not.
AB  - Direct primary care (DPC) occupies only a small niche in the health care payment
      system. But proponents say that federal legislation that would allow people to
      pay the monthly fee with health savings account dollars would help DCP take off.

PMID- 29068307
TI  - And the Oscar (Health) Goes to Cleveland (Clinic).
AB  - Oscar Health, a small insurer with big ambitions, has been enlisted to assist the
      storied Cleveland Clinic launch its own health plan. Each member of the plan will
      be matched with a care team made up of primary care provider, physician
      assistants, and other health care professionals.

PMID- 29068308
TI  - Wilson-Cook's Flourish Device Uses Magnets To Fix Pediatric Esophageal Atresia.
AB  - EA, although uncommon, is a complex and dangerous newborn birth defect with,
      until now, only chest surgical approaches. The Flourish Pediatric Esophageal
      Atresia Device is a remarkable alternative to traditional chest surgical
      procedures. No procedure or device is free of adverse events, but the results
      with this are so far impressive.

PMID- 29068309
TI  - Physician Compensation: Let Form Follow Function.
AB  - In true accountable, outcomes-driven models, there is an implicit expectation
      that physicians, payers, and other caregivers will be working together in new and
      collaborative ways. This introduces entire new layers of time and effort as new
      processes must be forged and evaluated, supported by investments in training,
      technology, and staff.

PMID- 29068310
TI  - Health Plans Start To Focus More On Social Needs of Beneficiaries.
AB  - Health plans have known for years that there are many non-health factors that
      play a role in a person's health and well being. Now a coterie of health plans is
      starting to tackle factors that were seen as being completely outside the purview
      of anyone in the health care system, let alone a health plan.

PMID- 29068311
TI  - Three Components Missing in Many Population-Management Strategies.
AB  - Many PHM strategies fall short because they fail to address three critical
      components that relate to patient-centeredness: patient-centered education,
      patient-centered social indicators, and patient-centered technology. Each of
      these three components is absolutely essential for population health strategies
      to work.

PMID- 29068312
TI  - The Role of Proteomic Testing in Improving Prognosis And Care Planning Quality
      Measures for Lung Cancer.
AB  - PURPOSE: The Oncology Care Model (OCM) is a payment model from the Centers for
      Medicare and Medicaid Services designed to reduce costs and improve quality in
      cancer care. Key components of quality for the OCM originate from the 13
      component cancer care plan. We surveyed the literature to understand the value of
      prognosis in OCM-directed planning for non-small-cell lung cancer (NSCLC) care
      and to investigate how the results of a prognostic, proteomic biomarker test, the
      VeriStrat test, can help OCM-participating providers meet the specific quality
      measures. DESIGN: A targeted literature review was supplemented by real-world
      author experience. METHODOLOGY: Available MEDLINE-indexed literature on the topic
      of lung cancer prognosis and cancer care planning (1997-2017) were reviewed.
      Authors also included relevant commentary based on their own real-world
      experience with VeriStrat testing and prognostic conversations. RESULTS: There
      was near-universal consensus in guidelines and literature about the critical
      importance of early, candid, and ongoing physician-patient discussions about
      prognosis, which informs most components of the OCM care plan. The VeriStrat test
      has been shown to provide accurate predictions of outcomes in all lines of
      therapy and in various treatments for patients with NSCLC, including
      chemotherapies and EGFR-TKI therapies. CONCLUSION: Accurate prognostic estimates,
      such as those provided by the VeriStrat test, are useful for predicting and
      documenting expected response to treatment, avoiding ineffective and costly
      overtreatment and for facilitating meaningful conversations with NSCLC patients
      about the timing of best supportive care and hospice care when appropriate,
      thereby improving cancer care planning and quality scores.

PMID- 29068316
TI  - Online Serum PFOA Calculator for Adults.
AB  - SUMMARY: Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant
      that has been detected in >100 public water systems in the United States alone. A
      variety of epidemiological investigations of PFOA have been published, mostly
      using measured or modeled serum PFOA concentrations as the exposure metric.
      Comparison of drinking water PFOA concentrations to those study findings or to
      typical serum concentrations requires pharmacokinetic modeling. This brief
      communication describes an online Javascript calculator that easily plots the
      expected serum PFOA concentration over time and at steady state for adults after
      starting or stopping consumption of PFOA-contaminated water. Two examples of
      usage are provided, including increasing serum PFOA after ongoing consumption of
      contaminated water at the federal limit, and decreasing serum PFOA after carbon
      filtration began in a contaminated water system. https://doi.org/10.1289/EHP2820.

PMID- 29068313
TI  - Phosphatidylinositol 4,5-bisphosphate optical uncaging potentiates exocytosis.
AB  - Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis.
      Classical ways of manipulating PI(4,5)P2 levels are slower than its metabolism,
      making it difficult to distinguish effects of PI(4,5)P2 from those of its
      metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which
      is loaded into cells in an inactive form and activated by light, allowing sub
      second increases in PI(4,5)P2 levels. By combining this compound with
      electrophysiological measurements in mouse adrenal chromaffin cells, we show that
      PI(4,5)P2 uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca2+
      sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant
      effector proteins. PI(4,5)P2 activation of exocytosis did not depend on the
      PI(4,5)P2-binding CAPS-proteins, suggesting that PI(4,5)P2 uncaging may bypass
      CAPS-function. Finally, PI(4,5)P2 uncaging triggered the rapid fusion of a subset
      of readily-releasable vesicles, revealing a rapid role of PI(4,5)P2 in fusion
      triggering. Thus, optical uncaging of signaling lipids can uncover their rapid
      effects on cellular processes and identify lipid effectors.

PMID- 29068317
TI  - After the Screening: What Happens Next for Children with Elevated Blood Lead?

PMID- 29068318
TI  - Advances in chemical sensing technologies for VOCs in breath for security/threat
      assessment, illicit drug detection, and human trafficking activity.
AB  - On-site chemical sensing of compounds associated with security and terrorist
      attacks is of worldwide interest. Other related bio-monitoring topics include
      identification of individuals posing a threat from illicit drugs, explosive
      manufacturing, as well as searching for victims of human trafficking and
      collapsed buildings. The current status of field analytical technologies is
      directed towards the detection and identification of vapours and volatile organic
      compounds (VOCs). Some VOCs are associated with exhaled breath, where research is
      moving from individual breath testing (volatilome) to cell breath (microbiome)
      and most recently to crowd breath metabolites (exposome). In this paper, an
      overview of field-deployable chemical screening technologies (both stand-alone
      and those with portable characteristics) is given with application to early
      detection and monitoring of human exposome in security operations. On-site
      systems employed in exhaled breath analysis, i.e. mass spectrometry (MS), optical
      spectroscopy and chemical sensors are reviewed. Categories of VOCs of interest
      include (a) VOCs in human breath associated with exposure to threat compounds,
      and (b) VOCs characteristic of, and associated with, human body odour (e.g.
      breath, sweat). The latter are relevant to human trafficking scenarios. New
      technological approaches in miniaturised detection and screening systems are also
      presented (e.g. non-scanning digital light processing linear ion trap MS (DLP-LIT
      MS), nanoparticles, mid-infrared photo-acoustic spectroscopy and hyphenated
      technologies). Finally, the outlook for rapid and precise, real-time field
      detection of threat traces in exhaled breath is revealed and discussed.

PMID- 29068314
TI  - A minimally sufficient model for rib proximal-distal patterning based on genetic
      analysis and agent-based simulations.
AB  - For decades, the mechanism of skeletal patterning along a proximal-distal axis
      has been an area of intense inquiry. Here, we examine the development of the
      ribs, simple structures that in most terrestrial vertebrates consist of two
      skeletal elements-a proximal bone and a distal cartilage portion. While the ribs
      have been shown to arise from the somites, little is known about how the two
      segments are specified. During our examination of genetically modified mice, we
      discovered a series of progressively worsening phenotypes that could not be
      easily explained. Here, we combine genetic analysis of rib development with agent
      based simulations to conclude that proximal-distal patterning and outgrowth could
      occur based on simple rules. In our model, specification occurs during somite
      stages due to varying Hedgehog protein levels, while later expansion refines the
      pattern. This framework is broadly applicable for understanding the mechanisms of
      skeletal patterning along a proximal-distal axis.

PMID- 29068315
TI  - Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of
      SCAP.
AB  - Cholesterol homeostasis is maintained through concerted action of the SREBPs and
      LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane
      ubiquitin ligase, participates in crosstalk between these critical signaling
      pathways. RNF145 expression is induced in response to LXR activation and high
      cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the
      expression of genes involved in cholesterol biosynthesis and reduces plasma
      cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated
      knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the
      expression of cholesterol biosynthetic genes and increases cholesterol levels
      both in liver and plasma. Mechanistic studies show that RNF145 triggers
      ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for
      COPII binding, potentially inhibiting its transport to Golgi and subsequent
      processing of SREBP-2. These findings define an additional mechanism linking
      hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.

PMID- 29068319
TI  - Microbiome associated with dentures malodour.
AB  - In the past, our inability to cultivate most of the oral microorganisms has
      limited our view of this complex ecosystem. In the present study, we utilized
      next generation deep sequencing techniques to revisit the microbiome associated
      with dentures malodour a growing problem with the rise in life expectancy. Study
      population comprised of twenty six full dentures patients (mean age 71+/-6.4, 16
      females) who visited the Tel Aviv University dental geriatric clinic. Dentures
      malodour was rated organoleptically by a single odour judge and dentures scored 2
      and above were considered malodour positive. DNA was extracted from the swab
      samples and analyzed using next generation deep sequencing 16S rDNA technology.
      Taxa identified could be classified into nine phyla, 29 genera and 117 species.
      Malodour positive samples showed a higher abundance of the phyla Firmicutes and
      Fusobacteria and the genera Veillonella, Fusobacterium and Porphyromonas with
      genera Leptotrichia, Atopobium, Megasphaera, Oribacterium and Campylobacter
      present only in the malodour positive group. Species level analysis demonstrated
      higher bacterial diversity within the malodourous samples and a clear division of
      two separate clusters representing the malodourous and non-malodour samples.
      Results of the present study show a clear difference between the microbial
      populations of malodourous and non-malodourous dentures both in composition and
      diversity.

PMID- 29068320
TI  - Osteogenic effects of simvastatin-loaded mesoporous titania thin films.
AB  - The use of statins in the field of bone regeneration is under current
      investigation due to the existing demand for non-toxic anabolic agents capable of
      enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme
      currently prescribed in clinics to inhibit cholesterol biosynthesis, has been
      proven to promote osteogenic differentiation by stimulating bone formation and
      inhibiting osteoclasts activity. We present the loading of simvastatin in
      mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this
      molecule with the demonstrated bioactivity of titania. TiO2 thin films processing
      and characterization were carried out, as well as evaluation of MC3T3-E1 pre
      osteoblasts viability when directly incubated with different concentrations of
      simvastatin, followed by the analysis of osteogenic activity promoted by
      simvastatin upon loading in the thin films. The accessible porosity of 36%
      quantified on the 95 +/- 5 nm thick mesoporous thin films, together with pore
      diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12
      +/- 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR
      spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability
      at concentrations <=0.01 g l-1, with a cytotoxicity threshold of 0.05 g l-1. We
      additionally found that film loadings with 0.001 g l-1 simvastatin promotes
      statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher
      concentration of 0.01 g l-1 leads to statistically higher osteogenic activity
      (ALP synthesis), after 21 days of incubation, as compared to unloaded films.
      These results demonstrate the potential of simvastatin local administration based
      on bioactive mesoporous thin films to promote pro-osteogenic properties. By
      focusing this strategy on the coating of metallic prostheses, the supply of
      simvastatin to the target tissue can be favored and risks of systemic side
      effects will be reduced while enhancing the osteointegration of the implants.

PMID- 29068321
TI  - Relationship between total serum immunoglobulin E levels, fractional exhaled
      breath nitric oxide levels and absolute blood eosinophil counts in atopic and non
      atopic asthma: a controlled comparative study.
AB  - OBJECTIVE: Asthma is a prevalent non-communicable disease both in low- and high
      income countries, including Nepal. Total serum immunoglobulin E levels and
      peripheral blood absolute eosinophil counts are known inflammatory markers of
      asthma. Fractional exhaled nitric oxide measurement in breath has also been
      proposed as a non-invasive biomarker to assess eosinophilic airway inflammation.
      This study explores the correlation between these three variables with the intent
      that one may replace the other in resource-limited setups. APPROACH: This
      prospective controlled trial evaluated 314 subjects with and without asthma, with
      the asthma group sub-divided into atopic and non-atopic categories. Total serum
      immunoglobulin E level, absolute eosinophil count in peripheral blood and
      fractional exhaled nitric oxide level were measured in all categories. RESULTS:
      The geometric mean of immunoglobulin E levels, absolute eosinophil count and
      fractional exhaled nitric oxide were 221.07 +/- 774.55 IU/mL, 214 +/- 360/uL and
      37 +/- 49 ppb in the asthma group and 59.13 +/- 174.32 IU/mL, 164 +/- 137/uL and
      12 +/- 21 ppb in the control group, respectively. Significantly higher levels
      were seen in the asthma group for total serum immunoglobulin E (p < 0.001), AEC
      (p = 0.002) and FENO (p < 0.001) levels. Total serum immunoglobulin E levels,
      absolute eosinophil count and fractional exhaled nitric oxide were 436.79 +/-
      822.40 IU/mL, 269 +/- 395/uL and 76 +/- 52 ppb in atopic asthma group. Similarly,
      total serum immunoglobulin E levels, absolute eosinophil count and fractional
      exhaled nitric oxide were 131.17 +/- 692.96 IU/mL, 182 +/- 328/uL and 23 +/- 22.5
      ppb in non-atopic asthma group. Significantly higher levels were seen in all
      three variables: tIgE (p < 0.001), AEC (p =  0.008) and FENO (p < 0.001). A
      moderate degree of positive correlation was identified between tIgE and FENO50
      (Spearman's rho = 0.461) and tIgE and AEC (Spearman's rho = 0.315) with only
      small correlation between FENO50 and AEC (Spearman's rho = 0.299). SIGNIFICANCE:
      tIgE levels, FENO50 and AEC levels are higher in asthma, specifically in the
      atopic phenotype, as compared to normal. Total serum IgE levels have moderate
      correlation with FENO50 and AEC but FENO50 and AEC are weakly correlated.

PMID- 29068323
TI  - Ethics, stakeholders and low doses.

PMID- 29068322
TI  - Adult skin-derived precursor Schwann cell grafts form growths in the injured
      spinal cord of Fischer rats.
AB  - In this study, GFP+ skin-derived precursor Schwann cells (SKP-SCs) from adult
      rats were grafted into the injured spinal cord of immunosuppressed rats. Our goal
      was to improve grafted cell survival in the injured spinal cord, which is
      typically low. Cells were grafted in hyaluronan-methylcellulose hydrogel (HAMC)
      or hyaluronan-methylcellulose modified with laminin- and fibronectin-derived
      peptide sequences (eHAMC). The criteria for selection of hyaluronan was for its
      shear-thinning properties, making the hydrogel easy to inject, methylcellulose
      for its inverse thermal gelation, helping to keep grafted cells in situ, and
      fibronectin and laminin to improve cell attachment and, thus, prevent cell death
      due to dissociation from substrate molecules (i.e., anoikis). Post-mortem
      examination revealed large masses of GFP+ SKP-SCs in the spinal cords of rats
      that received cells in HAMC (5 out of n = 8) and eHAMC (6 out of n = 8). Cell
      transplantation in eHAMC caused significantly greater spinal lesions compared to
      lesion and eHAMC only control groups. A parallel study showed similar masses in
      the contused spinal cord of rats after transplantation of adult GFP+ SKP-SCs
      without a hydrogel or immunosuppression. These findings suggest that adult GFP+
      SKP-SCs, cultured/transplanted under the conditions described here, have a
      capacity for uncontrolled proliferation. Growth-formation in pre-clinical
      research has also been documented after transplantation of: human induced
      pluripotent stem cell-derived neural stem cells (Itakura et al 2015 PLoS One 10
      e0116413), embryonic stem cells and embryonic stem cell-derived neurons
      (Brederlau et al 2006 Stem Cells 24 1433-40; Dressel et al 2008 PLoS One 3
      e2622), bone marrow derived mesenchymal stem cells (Jeong et al 2011 Circ. Res.
      108 1340-47) and rat nerve-derived SCs following in vitro expansion for >11
      passages (Funk et al 2007 Eur. J. Cell Biol. 86 207-19; Langford et al 1988 J.
      Neurocytology 17 521-9; Morrissey et al 1991 J. Neurosci. 11 2433-42). It is of
      upmost importance to define the precise culture/transplantation parameters for
      maintenance of normal cell function and safe and effective use of cell therapy.

PMID- 29068324
TI  - Risk factors for acute cholecystitis and for intraoperative complications.
AB  - BACKGROUND: Acute cholecystitis is still frequent in emergency surgical
      departments. As surgical technique, nowadays laparoscopy is widely used and with
      low complications and with low postoperative morbidity. MATERIAL AND METHODS: We
      perform an analytical study about the safety of laparoscopic surgery in patients
      with acute cholecystitis in a single Surgical Department with an experience of
      over 20 years in laparoscopic surgery. We included 193 patient admitted in our
      department during 2014 and 2015. RESULTS: Of the 193 patients, 43% were diagnosed
      with acute lithiasic cholecystitis (ALC) whereas 56% had chronic lithiasic
      cholecystitis (CLC). We assessed the comorbidities of the patient via Pearson's
      Chi-Square test and we found out that there is a significant relationship between
      acute cholecystitis and high blood tension, obesity and diabetes. Surgical
      techniques performed were in 95% of cases laparoscopic cholecystectomy and only
      in 5% we performed open surgery. DISCUSSIONS: Experienced surgeons have a lower
      conversion rate as compared to less experienced surgeons. For this reason,
      postoperative assessment criteria have been proposed, with a view to identify the
      risk of conversion CONCLUSION: In our study laparoscopic surgery for acute
      cholecystitis is a safe procedure with low intraoperative complication rate and
      with a reduced hospital stay. KEY WORDS: Acute cholecystitis, Intraoperative
      adhesion, Intraoperative bleeding, Laparoscopic cholecystectomy.

PMID- 29068325
TI  - Methods of ammonia removal in anaerobic digestion: a review.
AB  - The anaerobic digestion of substrates with high ammonia content has always been a
      bottleneck in the methanisation process of biomasses. Since microbial communities
      in anaerobic digesters are sensitive to free ammonia at certain conditions, the
      digestion of nitrogen-rich substrates such as livestock wastes may result in
      inhibition/toxicity eventually leading to process failures, unless appropriate
      engineering precautions are taken. There are many different options reported in
      literature to remove ammonia from anaerobic digesters to achieve a safe and
      stable process so that along with high methane yields, a good quality of
      effluents can also be obtained. Conventional techniques to remove ammonia include
      physical/chemical methods, immobilization and adaptation of microorganisms, while
      novel methods include ultrasonication, microwave, hollow fiber membranes and
      microbial fuel cell applications. This paper discusses conventional and novel
      methods of ammonia removal from anaerobic digesters using nitrogen-rich
      substrates, with particular focus on recent literature available about this
      topic.

PMID- 29068326
TI  - Swine manure treatment by anaerobic membrane bioreactor with carbon, nitrogen and
      phosphorus recovery.
AB  - Swine manure wastewater was treated in an anaerobic membrane bioreactor (AnMBR)
      that combined a continuous stirred tank reactor (CSTR) and a hollow-fiber
      ultrafiltration membrane, and the feasibility of ammonia and phosphorus recovery
      in the permeate was investigated. The AnMBR system was operated steadily with a
      high mixed liquor suspended solids (MLSS) concentration of 32.32 +/- 6.24 g/L for
      120 days, achieving an average methane yield of 280 mL/gVSadded and total
      chemical oxygen demand removal efficiency of 96%. The methane yield of the AnMBR
      is 83% higher than that of the single CSTR. The membrane fouling mechanism was
      examined, and MLSS and the polysaccharide contents of the extracellular polymeric
      substances were found to be the direct causes of membrane fouling. The effects of
      the permeation/relaxation rate and physical, chemical cleaning on membrane
      fouling were assessed for membrane fouling control, and results showed that a
      decrease in the permeation/relaxation rate together with chemical cleaning
      effectively reduced membrane fouling. In addition, a crystallization process was
      used for ammonia and phosphorus recovery from the permeate, and pH 9 was the
      optimal condition for struvite formation. The study has an instructive
      significance to the industrial applications of AnMBRs in treating high strength
      wastewater with nutrient recovery.

PMID- 29068327
TI  - How well-mixed is well mixed? Hydrodynamic-biokinetic model integration in an
      aerated tank of a full-scale water resource recovery facility.
AB  - Current water resource recovery facility (WRRF) models only consider local
      concentration variations caused by inadequate mixing to a very limited extent,
      which often leads to a need for (rigorous) calibration. The main objective of
      this study is to visualize local impacts of mixing by developing an integrated
      hydrodynamic-biokinetic model for an aeration compartment of a full-scale WRRF.
      Such a model is able to predict local variations in concentrations and thus
      allows judging their importance at a process level. In order to achieve this,
      full-scale hydrodynamics have been simulated using computational fluid dynamics
      (CFD) through a detailed description of the gas and liquid phases and validated
      experimentally. In a second step, full ASM1 biokinetic model was integrated with
      the CFD model to account for the impact of mixing at the process level. The
      integrated model was subsequently used to evaluate effects of changing influent
      and aeration flows on process performance. Regions of poor mixing resulting in
      non-uniform substrate distributions were observed even in areas commonly assumed
      to be well-mixed. The concept of concentration distribution plots was introduced
      to quantify and clearly present spatial variations in local process
      concentrations. Moreover, the results of the CFD-biokinetic model were concisely
      compared with a conventional tanks-in-series (TIS) approach. It was found that
      TIS model needs calibration and a single parameter set does not suffice to
      describe the system under both dry and wet weather conditions. Finally, it was
      concluded that local mixing conditions have significant consequences in terms of
      optimal sensor location, control system design and process evaluation.

PMID- 29068328
TI  - Study of the degradation in aqueous solution of a refractory organic compound:
      avermectin type used as pesticide in agriculture.
AB  - We examined the removal of abamectin by the electro-Fenton (EF) process and the
      feasibility of biological treatment after degradation. The effect of the
      operating parameters showed that abamectin (Aba) degradation was enhanced with
      increasing temperature. Response surface analysis of the central composite design
      led to the following optimal conditions for the abatement of chemical oxygen
      demand: 45.5  degrees C, 5 mg L-1, 150 mA, and 0.15 mmol L-1 for the temperature,
      initial Aba concentration, current intensity, and catalyst concentration,
      respectively. Under these conditions, 68.01% of the organic matter was removed
      and 94% of Aba was degraded after 5 h and 20 min of electrolysis, respectively. A
      biodegradability test, which was performed on a solution electrolyzed at 47 
      degrees C, 9 mg L-1, 150 mA, and 0.15 mmol L-1, confirms that the ratio of
      biological oxygen demand/chemical oxygen demand increased appreciably from 0.0584
      to 0.64 after 5 h of electrolysis. This increased ratio is slightly above the
      limit of biodegradability (0.4). These results show the relevance of the EF
      process and its effectiveness for abamectin degradation. We conclude that
      biological treatment can be combined with the EF process for total
      mineralization.

PMID- 29068329
TI  - Effect of permanent magnetic field on scale inhibition property of circulating
      water.
AB  - Effect of a permanent magnet field on the scale inhibition property of
      circulating water was investigated. Orthogonal experiments of L16(45) were
      performed and analyzed using the range analysis method. The operating parameters
      included magnetic field intensity, initial concentration of Ca2+ and Mg2+,
      magnetic treatment time, temperature, and flow velocity. Scale inhibition rate,
      hardness, relative variation in the proportion of free water molecules,
      electrical conductivity, and relative variation of molecular energy were chosen
      as the objectives. In addition, the morphology and the composition of CaCO3 and
      MgCO3 scale were studied by X-ray diffraction analysis. The optimal conditions
      were initial concentration of 900 mg/L, magnetic field intensity of 0.5 T,
      temperature of 303 K, time of 54 h and flow velocity of 0.17 m/s. The nuclear
      magnetic resonance results demonstrated that the number of hydrogen bonds
      increased between water molecules and hydrated ions. The magnetic field can
      promote the increase in the number of hydrogen bonds, which can inhibit the
      formation of calcium and magnesium carbonate precipitation. Moreover, the ratio
      of calcite, aragonite and vaterite will be changed at different magnetic field
      intensities, and the aragonite ratio will reach the peak at the optimum
      conditions.

PMID- 29068331
TI  - Performance evaluation of a large sewage treatment plant in Brazil, consisting of
      an upflow anaerobic sludge blanket reactor followed by activated sludge.
AB  - The objective of this study was to evaluate the behaviour of a system comprising
      an upflow anaerobic sludge blanket reactor followed by activated sludge to treat
      domestic sewage. The Betim Central sewage treatment plant, Brazil, was designed
      to treat a mean influent flow of 514 L/s. The study consisted of statistical
      treatment of monitoring data from the treatment plant covering a period of 4
      years. This work presents the concentrations and removal efficiencies of the main
      constituents in each stage of the treatment process, and a mass balance of
      chemical oxygen demand (COD) and nitrogen. The results highlight the good overall
      performance of the system, with high mean removal efficiencies: BOD (biochemical
      oxygen demand) (94%), COD (91%), ammonia (72%) and total suspended solids (92%).
      As expected, this system was not effective for the removal of nutrients, since it
      was not designed for this purpose. The removal of Escherichia coli (99.83%) was
      higher than expected. There was no apparent influence of operational and design
      parameters on the effluent quality in terms of organic matter removal, with the
      exceptions of the BOD load upstream of the aeration tank and the sludge age in
      the unit. Results suggest that this system is well suited for the treatment of
      domestic sewage.

PMID- 29068330
TI  - Photocatalytic degradation of Direct yellow 86 diazo dye using sulfanilic acid
      modified TiO2 in aqueous suspensions.
AB  - This study synthesized sulfanilic acid (SA)-modified TiO2 nanocomposites and used
      them as an effective photocatalyst for Direct yellow 86 diazo dye removal from
      aqueous solution. This novel nanocomposite (SA/TiO2) was characterized by Fourier
      transform infrared spectroscopy (FTIR), scanning electron microscopy and X-ray
      diffraction. The results showed the formation of SA/TiO2 nanocatalyst. The
      photocatalytic activity of the modified photocatalyst was examined by degradation
      of Direct yellow 86 (GE) under UV and visible light. The effects of five
      parameters, the concentration of GE, dosage of SA/TiO2 nanocomposite, UV light
      irradiation intensity, pH and visible light illumination, on the removal of GE
      using SA/TiO2 nanocomposite were studied. The highest GE removal was determined
      at pH of 9, nanocomposite dosage of 0.15 g/l and initial GE concentration of 50
      mg/l at the constant temperature of 25  degrees C. However, the results showed
      that the GE removal rate increased as the UV light intensity increased. In
      addition, an enhancement in the photodegradation rate was observed with visible
      light illumination. The adsorption trends of GE at various initial concentrations
      followed the Langmuir isotherm model.

PMID- 29068332
TI  - Optimization of paper mill industry wastewater treatment by electrocoagulation
      and electro-Fenton processes using response surface methodology.
AB  - This study deals with chemical oxygen demand (COD), phenol and Ca+2 removal from
      paper mill industry wastewater by electrocoagulation (EC) and electro-Fenton (EF)
      processes. A response surface methodology (RSM) approach was employed to evaluate
      the effects and interactions of the process variables and to optimize the
      performance of both processes. Significant quadratic polynomial models were
      obtained (R2 = 0.959, R2 = 0.993 and R2 = 0.969 for COD, phenol and Ca+2 removal,
      respectively, for EC and R2 = 0.936, R2 = 0.934 and R2 = 0.890 for COD, phenol
      and Ca+2 removal, respectively). Numerical optimization based on desirability
      function was employed; in a 27.55 min trial, 34.7% of COD removal was achieved at
      pH 9 and current density 96 mA/cm2 for EC, whereas in a 30 min trial, 74.31% of
      COD removal was achieved at pH 2 and current density 96 mA/cm2 and H2O2/COD molar
      ratio 2.0 for EF. The operating costs were calculated to be 6.44 ?/m3 for EC and
      7.02 ?/m3 for EF depending on energy and electrode consumption at optimum
      conditions. The results indicate that the RSM is suitable for the design and
      optimization of both of the processes. However, EF process was a more effective
      technology for paper mill industry wastewater treatment as compared with EC.

PMID- 29068333
TI  - Bed turbulent kinetic energy boundary conditions for trapping efficiency and
      spatial distribution of sediments in basins.
AB  - The purpose of this study is to develop and validate a numerical tool for
      evaluating the performance of a settling basin regarding the trapping of
      suspended matter. The Euler-Lagrange approach was chosen to model the flow and
      sediment transport. The numerical model developed relies on the open source
      library OpenFOAM(r), enhanced with new particle/wall interaction conditions to
      limit sediment deposition in zones with favourable hydrodynamic conditions (shear
      stress, turbulent kinetic energy). In particular, a new relation is proposed for
      calculating the turbulent kinetic energy threshold as a function of the
      properties of each particle (diameter and density). The numerical model is
      compared to three experimental datasets taken from the literature and collected
      for scale models of basins. The comparison of the numerical and experimental
      results permits concluding on the model's capacity to predict the trapping of
      particles in a settling basin with an absolute error in the region of 5% when the
      sediment depositions occur over the entire bed. In the case of sediment
      depositions localised in preferential zones, their distribution is reproduced
      well by the model and trapping efficiency is evaluated with an absolute error in
      the region of 10% (excluding cases of particles with very low density).

PMID- 29068334
TI  - Chemical fingerprinting of saline water intrusion into sewage lines.
AB  - High salinity in sewage sludge can affect not only the operation of wastewater
      treatment plants (WWTPs) but also the quality of treated water generated, thereby
      limiting its downstream reuse. Using data on geochemical parameters, both for the
      central WWTP in Abu Dhabi, UAE, and literature values for potential regional
      saline water sources (e.g., shallow groundwater and regional Arabian Gulf
      seawater), a variety of chemical fingerprinting diagnostic ratios were calculated
      and plotted in order to determine the source of salinity in the municipal sewage.
      Data were compared with data from a regional WWTP that was not impacted by
      salinity. Monitoring data demonstrated persistently elevated levels of salinity
      in the municipal wastewater arriving at the central WWTP from the city.
      Dilution/concentration analysis using a conductivity vs. chloride plot showed
      both potential sources, i.e. Arabian Gulf seawater and coastal hypersaline
      groundwater, as feasible sources of wastewater salinization. Further diagnostic
      analysis using a Panno Plot indicated that coastal groundwater was the only
      likely source of salinization of municipal sewage. Additional confirmation of the
      identity of the source and the extent of mixing using different lines of evidence
      like stable isotope ratios is recommended for future study.

PMID- 29068335
TI  - Black-odor water analysis and heavy metal distribution of Yitong River in
      Northeast China.
AB  - The black-odor mechanism of Yitong River was analyzed based on survey and
      monitoring results. We found that organic matter is the main pollution source of
      Yitong River and its tributaries. A black-odor evaluation model that can describe
      the pollution of the Yitong River water system was developed, and this model has
      the parameters I = 0.21 [CODCr] + 0.18 [DO] - 0.36[NH3-N] + 0.91. The model
      performance was satisfactory with a black-odor defining accuracy of 69%.
      Moreover, we found that CODCr, NH3-N, and DO are the influential factors of the
      Yitong River black-odor water body and that their threshold values when the water
      body transitioned to black odor were 109.2, 1.90, and 7.50 mg.L-1, respectively.
      We found that most of the Yitong River was polluted by six heavy metals, namely,
      As, Cd, Cr, Cu, Pb, and Zn. We used the Nemerow method to calculate the heavy
      metal pollution degree of each sampling point and found that 60% of the points
      were seriously polluted. Furthermore, we drew the heavy metal pollution
      distribution map of the Yitong River. Finally, we proposed an effective measure
      called new-type multistep constructed wetland to improve the water quality of
      Yitong River.

PMID- 29068336
TI  - Operation of an anaerobic filter compared with an anaerobic moving bed bioreactor
      for the treatment of waste water from hydrothermal carbonisation of fine mulch.
AB  - This experimental study investigates the anaerobic digestion of waste water from
      hydrothermal carbonisation of fine mulch (wood chips) in combination with a co
      substrate for the first time. Two anaerobic reactors, an anaerobic filter (AF)
      and an anaerobic moving bed bioreactor (AnMBBR), were operated over a period of
      131 days at mesophilic conditions. The organic loading rate was increased to a
      maximum of 8.5 g L-l d-1 in the AF and the AnMBBR. Both reactors achieved
      similarly efficient chemical oxygen demand removal rates of 80% approximately
      (approx.) and high methane production rates of approx. 2.7 L L-1 d-1.
      Nevertheless, signs of an inhibition were observed during the experiments.

PMID- 29068337
TI  - An efficient method to improve the production of methane from anaerobic digestion
      of waste activated sludge.
AB  - Methane production from waste activated sludge (WAS) anaerobic digestion is
      always low due to slow hydrolysis rate and inappropriate ratio of carbon to
      nitrogen (C/N). In this work, a novel approach, i.e., co-digestion of WAS and
      tobacco waste (TW) using ozone pretreatment, to greatly enhance the production of
      methane is reported. Experimental results showed the optimal C/N and ozone dosage
      for methane production was 24:1 and 90 mg/g suspended solids, and the
      corresponding methane production was 203.6 mL/g volatile suspended solids, which
      was 1.3-fold that in mono-WAS digestion. Further investigation showed the co
      digestion of WAS and TW was beneficial to the consumptions of protein and
      cellulose; also, the presence of ozone enhanced the disruption of organic
      substrates and production of short chain fatty acids, which provided sufficient
      digestion substrates for methane generation. Analysis of microbial community
      structure suggested that members of the phyla Bacteroidetes and Firmicutes were
      the dominant species when ozone pretreatment was applied. The findings obtained
      in this work might be of great importance for the treatment of WAS and TW.

PMID- 29068338
TI  - Ultrasonic selectivity on depressing photosynthesis of cyanobacteria and green
      algae probed by chlorophyll-a fluorescence transient.
AB  - Ultrasound can inhibit cyanobacterial growth through rupturing cells, but this
      pathway frequently has the risk to release intercellular toxin (e.g.,
      microcystin). Depressing photosynthesis without cell disruption may provide a new
      strategy to control cyanobacterial blooms using ultrasound, especially
      Microcystis blooms. In this work, Microcystis aeruginosa (toxic cyanobacteria)
      and Chlorella pyrenoidosa (typical green algae) were chosen as model microalgae
      to verify this hypothesis. Results showed that ultrasound has the ability to
      inhibit cyanobacterial photosynthesis significantly and selectively.
      Specifically, sonication damaged QA, a tightly bound one-electron acceptor, and
      blocked electron flow at QB, a two-electron acceptor, in the photosystem II
      (PSII) of M. aeruginosa when it was exposed for 60 s (35 kHz, 0.043 W/cm3).
      Moreover, 44.8% of the reaction centers (RCs) in the PSII of M. aeruginosa were
      transferred into inactive ones (RCsis), and the cell concentration decreased by
      32.5% after sonication for 300 s. By contrast, only 7.9% of RCsi occurred in C.
      pyrenoidosa, and cell concentration and chlorophyll-a content reduced by 18.7%
      and 9.3%, respectively. Differences in both species (i.e., cell structures) might
      be responsible for the varying levels to sonication. This research suggests that
      cyanobacteria, especially Microcystis, could be controlled by ultrasound via
      damaging their PSIIs.

PMID- 29068339
TI  - Synthesis of carboxyl-introduced chitosan with C2 amine groups protected and its
      use in copper (II) removal.
AB  - A route for the formation of carboxyl-introduced chitosan (CI-CS) with C2 amine
      groups protected (CIAP-CS) was investigated to improve copper (II) adsorption.
      First, the C2 amine groups of the chitosan (CS) were protected via a Schiff-base
      reaction by benzaldehyde. Then the product was obtained by the introduction of
      pyromellitic dianhydride to the C6 hydroxyl groups on CS via epichlorohydrin. The
      last product was obtained by removing the Schiff base with dilute hydrochloride
      solution. CI-CS without C2 amine groups protected was directly synthesized as
      well. The adsorbents were characterized by Fourier transform infrared (FTIR), X
      ray diffraction (XRD) and X-ray photoelectron spectrometer (XPS). The adsorption
      properties for copper (II) were investigated. FTIR spectroscopy and XPS clearly
      showed that most of the amine groups in CS were converted to -N = CH2 groups
      after the benzaldehyde treatment and that no cross-linking reactions with CS were
      involved; the HCl treatment after the cross-linking reaction effectively released
      nitrogen atoms protected into the form of the primary amine again. The results
      confirm that the CIAP-CS cross-linked with the new method had significantly
      greater adsorption capacities than the CI-CS cross-linked directly with CS.
      Mechanism study revealed that the increased adsorption performance is attributed
      to the large number of primary carboxyl and amine groups available on the
      surfaces of the CIAP-CS. The adsorption mechanism is based on ion exchange and
      chelating action, and the adsorption process is mainly chemisorption.

PMID- 29068340
TI  - Simultaneous removal of aqueous Zn2+, Cu2+, Cd2+, and Pb2+ by zeolites
      synthesized from low-calcium and high-calcium fly ash.
AB  - In this study, zeolites were synthesized from low-calcium (LCZ) and high-calcium
      (HCZ) fly ash, respectively. Subsequently, the zeolites were tested for their
      removal effectiveness for four aqueous cations, namely, Zn2+, Cu2+, Cd2+, and
      Pb2+, as a function of contact time, pH value, adsorbent dosage, and initial
      concentration of heavy metals. Both zeolites were characterized by X-ray
      diffraction, X-ray fluorescence spectrometry, scanning electron microscopy,
      specific surface area, and cation exchange capacity. The results show that HCZ
      mainly consists of an unnamed zeolite (Na6[AlSiO4]6.4H2O), whereas LCZ mainly
      consists of faujasite-type zeolite. The optimum sorption conditions were pH =
      6.0; adsorbent dosage = 1.0 g.L-1; temperature = 25  degrees C; contact time =
      100 min; and initial heavy metal concentration = 100 mg.L-1. The sorption
      kinetics of the four aqueous cations on both LCZ and HCZ followed the pseudo
      second-order kinetic model, and the sorption isotherm data fitted well with the
      Langmuir isotherm model. For LCZ, the maximum adsorption capacities of Zn2+,
      Cu2+, Cd2+, and Pb2+ were 155.76, 197.86, 123.76, and 186.22 mg.g-1,
      respectively. For HCZ, the values were 154.08, 183.15, 118.91, and 191.94 mg.g-1,
      respectively. The zeolites were regenerated by NaCl solution (1 mol.L-1) and
      showed high removal efficiency. In conclusion, zeolites produced by fly ash are
      promising materials for removing Zn2+, Cu2+, Cd2+, and Pb2+ from wastewater.

PMID- 29068341
TI  - Synthesis of coral-globular-like composite Ag/TiO2-SnO2 and its photocatalytic
      degradation of rhodamine B under multiple modes.
AB  - Taking cetyltrimethylammonium bromide (CTAB) as the template and using TiO2 as
      the substrate, coral-globular-like composite Ag/TiO2-SnO2 (CTAB) was successfully
      synthesized by the sol-gel combined with a temperature-programmed treatment
      method. X-ray diffraction, scanning electron microscopy (SEM), UV-vis diffuse
      reflectance spectroscopy, X-ray photoelectron spectroscopy, SEM combined with X
      ray energy dispersive spectroscopy, and N2 adsorption-desorption tests were
      employed to characterize samples' crystalline phase, chemical composition,
      morphology and surface physicochemical properties. Results showed that composites
      not only had TiO2 anatase structure, but also had some generated SnTiO4, and the
      silver species was metallic Ag0. Ag/TiO2-SnO2 (CTAB) possessed a coral-globular
      like structure with nanosheets in large quantities. The photocatalytic activity
      of Ag/TiO2-SnO2 (CTAB) had studied by degrading organic dyes under multi-modes,
      mainly using rhodamine B as the model molecule. Results showed that the coral
      globular-like Ag/TiO2-SnO2 (CTAB) was higher photocatalytic activity than that of
      commercial TiO2, Ag/TiO2-SnO2, TiO2-SnO2 (CTAB), and TiO2-SnO2 under ultraviolet
      light irradiation. Moreover, Ag/TiO2-SnO2 (CTAB) composite can significantly
      affect the photocatalytic degradation under multi-modes including UV light,
      visible light, simulated solar light and microwave-assisted irradiation.
      Meanwhile, the photocatalytic activity of Ag/TiO2-SnO2 (CTAB) was maintained even
      after three cycles, indicating that the catalyst had good usability.

PMID- 29068342
TI  - Investigation into the long-term stormwater pollution removal efficiency of
      bioretention systems.
AB  - In recent years, there has been a steady increase in the number of bioretention
      systems installed worldwide. However, there has only been limited research on the
      long-term effectiveness of these sustainable urban drainage system devices. This
      paper presents the results of a series of controlled field experiments
      investigating the pollutant removal efficiency of three, 10-year-old, bio
      filtration systems that have been in service in the Sunshine Coast in Australia.
      The results of this study suggest that the long-term pollution removal
      performance of these systems may not be as effective as previously thought and
      further research is needed.

PMID- 29068343
TI  - The influence of particle size on the first flush strength of urban stormwater
      runoff.
AB  - The presence of a first flush (FF) of suspended solids (SS) in stormwater runoff
      has important implications for the design of treatment facilities, as does the
      particle size of solids. Whilst numerous studies have examined the FF behaviour
      of SS, few have disaggregated FF trends by particle size. In this study, the FF
      behaviour of SS was investigated in five size ranges, sampled from an urban
      stormwater drainage system located in Dublin, Ireland. A weak FF was exhibited in
      the gross fraction of SS, with just two events from 14 transporting more than 50%
      of the SS mass in the first 25% of runoff, implying that treatment structures
      should be capable of removing SS throughout the storm event. In the majority of
      rain events, the FF strength increased with decreasing particle size, probably
      related to the lower intensities required to dislodge solids at the onset of
      rainfall. Although FF strength was correlated with rain event characteristics,
      prediction intervals were too broad to confirm FF presence based on rainfall data
      alone. Therefore, the design of smaller treatment volumes based on an assumption
      of FF must be justified by local monitoring data.

PMID- 29068344
TI  - Surface water polycyclic aromatic hydrocarbons (PAH) in urban areas of Nanjing,
      China.
AB  - The concentration, sources and environmental risks of polycyclic aromatic
      hydrocarbons (PAHs) in surface water in urban areas of Nanjing were investigated.
      The range of ?16PAHs concentration is between 4,076 and 29,455 ng/L, with a mean
      of 17,212 ng/L. The composition of PAHs indicated that 2- and 3-ring PAHs have
      the highest proportion in all PAHs, while the 5- and 6-ring PAHs were the least
      in proportion. By diagnostic ratio analysis, combustion and petroleum were a
      mixture input that contributed to the water PAH in urban areas of Nanjing.
      Positive matrix factorization quantitatively identified four factors, including
      coke oven, coal combustion, oil source, and vehicle emission, as the main
      sources. Toxic equivalency factors of BaP (BaPeq) evaluate the environmental
      risks of PAHs and indicate the PAH concentration in surface water in urban areas
      of Nanjing had been polluted and might cause potential environmental risks.
      Therefore, the PAH contamination in surface water in urban areas of Nanjing
      should draw considerable attention.

PMID- 29068345
TI  - Field study on N2O emission from subsurface wastewater infiltration system under
      variable loading rates and drying-wetting cycles.
AB  - In this field study, the impacts of influent loadings and drying-wetting cycles
      on N2O emission in a subsurface wastewater infiltration (SWI) system were
      investigated. N2O emitted under different operation conditions were quantified
      using static chamber and gas chromatograph techniques. N2O conversion rate
      decreased from 6.6 +/- 0.1% to 2.7 +/- 0.1% with an increase in hydraulic loading
      (HL) from 0.08 to 0.24 m3/m2.d. By contrast, N2O conversion rate increased with
      increasing pollutant loading (PL) up to 8.2 +/- 0.5% (PL 4.2 g N/m2.d) above
      which conversion rate decreased, confirming that N2O production was under the
      interaction of nitrification and denitrification. Taking into consideration the
      pollutants (chemical oxygen demand (COD), NH4+-N, NO3--N and total nitrogen (TN))
      removal ratio and N2O emission, optimal loading ranges and drying-wetting modes
      were suggested as HL 0.08-0.12 m3/m2.d, PL 3.2-3.7 g N/m2.d and 12 h:12 h,
      respectively. The results revealed that in SWI systems, conversion ratio of
      influent nitrogen to N2O could be between 4.5% and a maximum of 7.0%.

PMID- 29068346
TI  - A novel three-stage bioreactor for the effective detoxification of sodium dodecyl
      sulphate from wastewater.
AB  - Anionic surfactants like sodium dodecyl sulphate (SDS), due to its extensive
      disposal to water bodies cause detrimental effects to the ecosystem. Among the
      various attempts to reduce the after effects of these toxicants, microbial
      induced bioremediation serves as a promising strategy. The current study aimed to
      develop a three stage bioreactor to remediate anionic surfactants in wastewater
      using effective bacterial isolates. Screening of effective SDS biodegraders led
      to isolation of Pseudomonas aeruginosa (MTCC 10311). Treatment of synthetic
      effluent with an immobilized packed bed reactor at a flow rate of 5 mL h-1
      resulted in 81 +/- 2% SDS eliminations and 70 +/- 1% reduction in chemical oxygen
      demand (COD) in five cycles (6 h per cycle). The hydraulic retention time of the
      reactor was found to be 6 h. Combinatorial usage of a three stage bioreactor,
      involving aeration, adsorption with low cost scrap rubber granules and treatment
      with immobilized Pseudomonas aeruginosa, successfully reduced SDS concentrations
      and COD of wastewater to 99.8 +/- 0.1% and 99 +/- 1%, respectively, in 18 h by
      continuous treatment. Half-life of the three stage bioreactor was 72 h. In
      addition to reducing the surfactant concentrations, this novel bioreactor could
      resolve the surfactant associated foaming problems in treatment plants, which
      make it more unique.

PMID- 29068347
TI  - The ecological risk assessment and suggestions on heavy metals in river sediments
      of Jinan.
AB  - The concentrations of eight heavy metals (Cr, Hg, As, Pb, Cd, Cu, Zn, Ni) in six
      river sediment samples were collected for evaluation of the degree of the heavy
      metals pollution distribution and ecological risk of three main rivers' sediments
      in Jinan. Multivariate statistical techniques were used to determine the most
      common pollution sources. The results illustrated that all of the metals in
      Damatou and Xinfengzhuang sections of the Xiaoqing River were much higher than
      the background value, and the level of potential ecological risk index was very
      high. The remaining four sections had a low or moderate degree of ecological
      risk. Principal component analysis (PCA) showed that all metals, with the
      exception of As, formed the first component explaining 86.85% of the total
      variance and industry sources could be considered as the first component, while
      As alone could be the second component, representing agricultural source. The
      elements Cr and Zn were grouped together while the remaining six metals formed a
      separate category. Among all heavy metals, Hg and Cd were the most significant
      contributors to the pollution. Therefore, the prevention of pollution should pay
      more attention to controlling the sources, especially Hg and Cd.

PMID- 29068348
TI  - Physico-chemical treatment of liquid waste on an industrial plant for
      electrocoagulation.
AB  - Wastewater from washing, oil separators, the metal processing and detergent
      industries, was tested and treated for treatment of different types of liquid
      waste at industrial level at Domzale-Kamnik Wastewater Treatment Plant (WWTP).
      The effect of implementing the electrocoagulation (EC) and flotation processes,
      respectively, is analysed and includes the duration of the EC implementation,
      voltage, number of electrodes, and chemical addition, as well as the pH effect
      and conductivity. The tests were performed not only on various types of liquid
      waste, but also on different mixtures of liquid waste. Laboratory analysis of the
      samples before and after EC have shown an effective reduction not only in organic
      loads in accordance with the COD (chemical oxygen demand) parameter, but also in
      mineral oil content, toxic metal concentration, and surfactants. The COD in
      liquid waste from the detergent industry was reduced by 73% and the content of
      surfactants by 64%. In liquid waste from the metal processing industry, the COD
      decreased by up to 95%, while the content of toxic metals decreased from 59 to
      99%. Similar phenomena were shown in liquid waste from oil separators, where the
      COD was reduced to 33% and the concentration of mineral oils by 99%. Some of the
      liquid wastes were mixed together in the ratio 1:1, thus allowing testing of the
      operation of EC technology in heterogeneous liquid waste, where the final result
      proved to be effective cleaning as well. After treatment in the process of EC,
      the limit values of the treated water proved appropriate for discharge into the
      sewerage system.

PMID- 29068349
TI  - Evaluation of virus recovery methods and efficiency of tannin-derived coagulants
      in removing total coliforms, E. coli and enteric viruses in effluents of a
      domestic sewage treatment plant.
AB  - In the present study, nine coagulants having potential to be used for sewage
      treatment were compared to assess their efficiency in removing total coliform
      bacteria, Escherichia coli and adenovirus. The coagulants tested were metallic
      and organic and their efficiency was compared when treating samples of raw and
      treated sewage (activated sludge). Before the efficiency tests of the coagulants,
      viral concentration methods were compared. Coagulation tests were carried out by
      using the jar-test system and the doses used ranged from 100 ppm to 1,000 ppm.
      Viral DNA was extracted and subjected to real-time polymerase chain reaction
      (qPCR) using primers for the gene of AdV hexon. Aluminum sulfate (1,000 ppm)
      presented the best results for raw sewage among metal coagulants whereas
      Acquapol(r) C118 and WW (1,000 ppm) had the most satisfactory results among
      organic coagulants, both reducing up to 7 logs for coliforms and 4 logs for
      virus. For the treated effluent, FeCl2 (1,000 ppm) presented best results for
      metal coagulants, whereas, from organic coagulants, the best removal rates were
      for Acquapol(r) 893/11 (1,000 ppm), both reducing up to 3 logs for coliforms and
      4 logs for virus.

PMID- 29068350
TI  - Chromium removal capability and photosynthetic characteristics of Cyperus
      alternifolius and Coix lacryma-jobi L. in vertical flow constructed wetland
      treated with hexavalent chromium bearing domestic sewage.
AB  - In this study, the chromium removal capability and photosynthetic capacity
      response of plants were investigated in vertical flow wetland microcosms (VFWM)
      treated with Cr(VI) bearing domestic sewage. Two plants, Cyperus alternifolius
      (C. alternifolius) and Coix lacryma-jobi L. (C. lacryma-jobi L.) grown in the
      VFWM enhanced the purification of Cr(VI) enriched domestic sewage. Cr
      concentration in the effluent fell below detection limit (<0.03 mg L-1), except
      for the C. alternifolius wetland treated with 40 mg L-1 Cr(VI). The biomasses of
      both plants species were increased at 10 and 20 mg L-1 Cr(VI) exposure but
      inhibited at 40 mg L-1 Cr(VI). The photosynthetic capacities of both plants were
      not affected at 10-40 mg L-1 Cr(VI) exposure during the days 20-60. However, they
      were inhibited significantly (P < 0.05) at 40 mg L-1 Cr(VI) exposure during days
      80-100. These results demonstrated that a VFWM with C. alternifolius and/or C.
      lacryma-jobi L. was capable of maintaining its efficiency and recovering its
      vegetation. VFWM with C. alternifolius and/or C. lacryma-jobi L. was promising
      for purifying wastewater which contains low to medium concentrations of Cr(VI)
      (<20 mg L-1).

PMID- 29068351
TI  - Augmenting granular activated carbon with natural clay for multicomponent
      sorption of heavy metals from aqueous solutions.
AB  - Multicomponent adsorption of Cd, Cr, Cu, Pb and Zn onto date palm pits based
      granular activated carbon (GAC) augmented with highly active natural clay at
      different proportion was investigated. The effects of the initial pH and the
      adsorbents mixed ratio on the removal selectivity sequence of the metals
      evaluated. Batch adsorption experiments were undertaken at initial pH 2, 6 and
      12. At initial pH 2, both the percent removal and the metals adsorptive capacity
      decreased with increasing GAC to clay ratio (from 0 to 1) with the percentage
      removal of Cd, Zn and Cr ions dropping from 68, 81, 100% to 43, 57 and 70%,
      respectively. At both pH 6 and 12, the percentage removals and adsorption
      capacities of all the heavy metal ions are higher than at pH 2. Selectivity
      sequences for pH 2, 6 and 12 followed the order Pb > Cr > Cu > Zn > Cd; Pb > Cr >
      Cu > Cd > Zn and Cd > Cr > Cu > Pb > Zn, respectively. The adsorption trends were
      analyzed in relation to point of zero charge and xi-potential and the metals ions
      speciation at different pH. These results will help better understand the
      feasibility of augmenting GAC with natural clay minerals during fixed bed column
      test which is more beneficial for practical industrial applications.

PMID- 29068352
TI  - Exploring aeration-associated energy savings at a conventional water reclamation
      plant.
AB  - Aeration accounts for a large fraction of energy consumption at conventional
      water reclamation plants (WRPs). Older plants were designed when control
      techniques were relatively primitive and energy consumption was less of a
      concern. As a result, although process operations at older WRPs can satisfy
      effluent permit requirements, they can operate with excess aeration. In this
      study, we developed a wastewater process model to evaluate possible aeration
      savings at the Metropolitan Water Reclamation District of Greater Chicago Calumet
      WRP, one of the oldest plants in Chicago. Based on subsets of influent
      characteristics, we identified eight steady-state scenarios. We also identified
      transient scenarios that included high probability perturbations and more
      challenging but lower probability conditions. Results indicate that the Calumet
      WRP frequently operates with excess aeration. Effluent dissolved oxygen is the
      limiting parameter with respect to aeration saving and permit requirements. In a
      typical storm event, aeration could be reduced by up to 50%; even under low
      probability challenging perturbations, aeration can be decreased by 35% from
      current average levels and all permit requirements can be satisfied. Annual cost
      savings from cutting the aeration by 35% could be more than $1.2 million.

PMID- 29068353
TI  - Multi-metals column adsorption of lead(II), cadmium(II) and manganese(II) onto
      natural bentonite clay.
AB  - The present work was aimed at evaluating the multi-metals column adsorption of
      lead(II), cadmium(II) and manganese(II) ions onto natural bentonite. The
      bentonite clay adsorbent was characterized for physical and chemical properties
      using X-ray diffraction, X-ray fluorescence, Brunauer-Emmett-Teller surface area
      and cation exchange capacity. The column performance was evaluated using
      adsorbent bed height of 5.0 cm, with varying influent concentrations (10 mg/L and
      50 mg/L) and flow rates (1.4 mL/min and 2.4 mL/min). The result shows that the
      breakthrough time for all metal ions ranged from 50 to 480 minutes. The maximum
      adsorption capacity was obtained at initial concentration of 10 mg/L and flow
      rate of 1.4 mL/min, with 2.22 mg/g of lead(II), 1.71 mg/g of cadmium(II) and 0.37
      mg/g of manganese(II). The order of metal ions removal by natural bentonite is
      lead(II) > cadmium(II) > manganese(II). The sorption performance and the dynamic
      behaviour of the column were predicted using Adams-Bohart, Thomas, and Yoon
      Nelson models. The linear regression analysis demonstrated that the Thomas and
      Yoon-Nelson models fitted well with the column adsorption data for all metal
      ions. The natural bentonite was effective for the treatment of wastewater laden
      with multi-metals, and the process parameters obtained from this work can be used
      at the industrial scale.

PMID- 29068355
TI  - Corrigendum: Water Science and Technology 75 (10), 2237-2245: The role of
      constructed wetlands for biomass production within the water-soil-waste nexus, C.
      T. Avellan et al., doi: 10.2166/wst.2017.106.

PMID- 29068354
TI  - Kinetic, isotherm and thermodynamic studies with linear and non-linear fitting
      for cadmium(II) removal by black carbon of pine cone.
AB  - In this study, black carbon from pine cone (BCPC) and acidic-modified BCPC
      (MBCPC) powder as a popular agricultural waste in the southeast of Iran were used
      for cadmium removal from aqueous solutions. The effect of various factors, such
      as surface chemistry and dosage of adsorbent, contact time, size of particles,
      initial concentration of cadmium, temperature, and pH of aqueous solutions, was
      investigated. The results show cadmium removal with usage of the mentioned
      adsorbents increased after acidic modification. It was noteworthy in this work
      that the removal percentage of pollutant was above 90% for suggested biosorbents.
      The obtained experimental data for optimum conditions were selected to model the
      adsorption behavior of the materials with usage of six isotherm equations via non
      linear fitting method and the residual root mean square error estimation for each
      model. The adsorption of cadmium preferably fitted Khan and Langmuir-Freundlich
      isotherms for BCPC and MBCPC adsorbents, respectively. The kinetic studies via
      linear fitting method proved the second-order kinetic was the applicable model
      for the adsorption process. Thermodynamic studies show the adsorption process of
      cadmium onto BCPC and MBCPC was spontaneous and endothermic.

PMID- 29068356
TI  - Defect Detection of Adhesive Layer of Thermal Insulation Materials Based on
      Improved Particle Swarm Optimization of ECT.
AB  - This paper studies the defect detection problem of adhesive layer of thermal
      insulation materials. A novel detection method based on an improved particle
      swarm optimization (PSO) algorithm of Electrical Capacitance Tomography (ECT) is
      presented. Firstly, a least squares support vector machine is applied for data
      processing of measured capacitance values. Then, the improved PSO algorithm is
      proposed and applied for image reconstruction. Finally, some experiments are
      provided to verify the effectiveness of the proposed method in defect detection
      for adhesive layer of thermal insulation materials. The performance comparisons
      demonstrate that the proposed method has higher precision by comparing with
      traditional ECT algorithms.

PMID- 29068358
TI  - Visual Localization across Seasons Using Sequence Matching Based on Multi-Feature
      Combination.
AB  - Visual localization is widely used in autonomous navigation system and Advanced
      Driver Assistance Systems (ADAS). However, visual-based localization in seasonal
      changing situations is one of the most challenging topics in computer vision and
      the intelligent vehicle community. The difficulty of this task is related to the
      strong appearance changes that occur in scenes due to weather or season changes.
      In this paper, a place recognition based visual localization method is proposed,
      which realizes the localization by identifying previously visited places using
      the sequence matching method. It operates by matching query image sequences to an
      image database acquired previously (video acquired during traveling period). In
      this method, in order to improve matching accuracy, multi-feature is constructed
      by combining a global GIST descriptor and local binary feature CSLBP (Center
      symmetric local binary patterns) to represent image sequence. Then, similarity
      measurement according to Chi-square distance is used for effective sequences
      matching. For experimental evaluation, the relationship between image sequence
      length and sequences matching performance is studied. To show its effectiveness,
      the proposed method is tested and evaluated in four seasons outdoor environments.
      The results have shown improved precision-recall performance against the state-of
      the-art SeqSLAM algorithm.

PMID- 29068357
TI  - Chronotropic Competence Indices Extracted from Wearable Sensors for
      Cardiovascular Diseases Management.
AB  - Chronotropic incompetence (CI) has been proven to be an important factor in the
      diagnosis and management of cardiovascular diseases. In this paper, we extend the
      existing CI parameters and propose chronotropic competence indices (CCI) to
      describe the exercise response of the cardiopulmonary system. A cardiac
      chronotropic competence Test (3CT), dedicated to CCI measurement using a wearable
      device, is also presented. Preliminary clinical trials are presented for the
      validation of 3CT measurement accuracy, and to show the potential of CCI in the
      prevention and rehabilitation of cardiovascular diseases.

PMID- 29068359
TI  - Securing Color Fidelity in 3D Architectural Heritage Scenarios.
AB  - Ensuring color fidelity in image-based 3D modeling of heritage scenarios is
      nowadays still an open research matter. Image colors are important during the
      data processing as they affect algorithm outcomes, therefore their correct
      treatment, reduction and enhancement is fundamental. In this contribution, we
      present an automated solution developed to improve the radiometric quality of an
      image datasets and the performances of two main steps of the photogrammetric
      pipeline (camera orientation and dense image matching). The suggested solution
      aims to achieve a robust automatic color balance and exposure equalization,
      stability of the RGB-to-gray image conversion and faithful color appearance of a
      digitized artifact. The innovative aspects of the article are: complete
      automation, better color target detection, a MATLAB implementation of the ACR
      scripts created by Fraser and the use of a specific weighted polynomial
      regression. A series of tests are presented to demonstrate the efficiency of the
      developed methodology and to evaluate color accuracy ('color characterization').

PMID- 29068361
TI  - Indoor Air Quality and Health.
AB  - In the last few decades, Indoor Air Quality (IAQ) has received increasing
      attention from the international scientific community, political institutions,
      and environmental governances for improving the comfort, health, and wellbeing of
      building occupants.[...].

PMID- 29068360
TI  - Soluble CD40 Ligand and Oxidative Response Are Reciprocally Stimulated during
      Shiga Toxin-Associated Hemolytic Uremic Syndrome.
AB  - Shiga toxin (Stx), produced by Escherichia coli, is the main pathogenic factor of
      diarrhea-associated hemolytic uremic syndrome (HUS), which is characterized by
      the obstruction of renal microvasculature by platelet-fibrin thrombi. It is well
      known that the oxidative imbalance generated by Stx induces platelet activation,
      contributing to thrombus formation. Moreover, activated platelets release soluble
      CD40 ligand (sCD40L), which in turn contributes to oxidative imbalance,
      triggering the release of reactive oxidative species (ROS) on various cellular
      types. The aim of this work was to determine if the interaction between the
      oxidative response and platelet-derived sCD40L, as consequence of Stx-induced
      endothelium damage, participates in the pathogenic mechanism during HUS.
      Activated human glomerular endothelial cells (HGEC) by Stx2 induced platelets to
      adhere to them. Although platelet adhesion did not contribute to endothelial
      damage, high levels of sCD40L were released to the medium. The release of sCD40L
      by activated platelets was inhibited by antioxidant treatment. Furthermore, we
      found increased levels of sCD40L in plasma from HUS patients, which were also
      able to trigger the respiratory burst in monocytes in a sCD40L-dependent manner.
      Thus, we concluded that platelet-derived sCD40L and the oxidative response are
      reciprocally stimulated during Stx2-associated HUS. This process may contribute
      to the evolution of glomerular occlusion and the microangiopathic lesions.

PMID- 29068363
TI  - Dolphin Sounds-Inspired Covert Underwater Acoustic Communication and Micro-Modem.
AB  - A novel portable underwater acoustic modem is proposed in this paper for covert
      communication between divers or underwater unmanned vehicles (UUVs) and divers at
      a short distance. For the first time, real dolphin calls are used in the modem to
      realize biologically inspired Covert Underwater Acoustic Communication (CUAC). A
      variety of dolphin whistles and clicks stored in an SD card inside the modem
      helps to realize different biomimetic CUAC algorithms based on the specified
      covert scenario. In this paper, the information is conveyed during the time
      interval between dolphin clicks. TMS320C6748 and TLV320AIC3106 are the core
      processors used in our unique modem for fast digital processing and
      interconnection with other terminals or sensors. Simulation results show that the
      bit error rate (BER) of the CUAC algorithm is less than 10 - 5 when the signal to
      noise ratio is over -5 dB. The modem was tested in an underwater pool, and a data
      rate of 27.1 bits per second at a distance of 10 m was achieved.

PMID- 29068362
TI  - Noise Maps for Quantitative and Clinical Severity Towards Long-Term ECG
      Monitoring.
AB  - Noise and artifacts are inherent contaminating components and are particularly
      present in Holter electrocardiogram (ECG) monitoring. The presence of noise is
      even more significant in long-term monitoring (LTM) recordings, as these are
      collected for several days in patients following their daily activities; hence,
      strong artifact components can temporarily impair the clinical measurements from
      the LTM recordings. Traditionally, the noise presence has been dealt with as a
      problem of non-desirable component removal by means of several quantitative
      signal metrics such as the signal-to-noise ratio (SNR), but current systems do
      not provide any information about the true impact of noise on the ECG clinical
      evaluation. As a first step towards an alternative to classical approaches, this
      work assesses the ECG quality under the assumption that an ECG has good quality
      when it is clinically interpretable. Therefore, our hypotheses are that it is
      possible (a) to create a clinical severity score for the effect of the noise on
      the ECG, (b) to characterize its consistency in terms of its temporal and
      statistical distribution, and (c) to use it for signal quality evaluation in LTM
      scenarios. For this purpose, a database of external event recorder (EER) signals
      is assembled and labeled from a clinical point of view for its use as the gold
      standard of noise severity categorization. These devices are assumed to capture
      those signal segments more prone to be corrupted with noise during long-term
      periods. Then, the ECG noise is characterized through the comparison of these
      clinical severity criteria with conventional quantitative metrics taken from
      traditional noise-removal approaches, and noise maps are proposed as a novel
      representation tool to achieve this comparison. Our results showed that neither
      of the benchmarked quantitative noise measurement criteria represent an accurate
      enough estimation of the clinical severity of the noise. A case study of long
      term ECG is reported, showing the statistical and temporal correspondences and
      properties with respect to EER signals used to create the gold standard for
      clinical noise. The proposed noise maps, together with the statistical
      consistency of the characterization of the noise clinical severity, paves the way
      towards forthcoming systems providing us with noise maps of the noise clinical
      severity, allowing the user to process different ECG segments with different
      techniques and in terms of different measured clinical parameters.

PMID- 29068364
TI  - Advances in Precision Medicine: Tailoring Individualized Therapies.
AB  - The traditional bench-to-bedside pipeline involves using model systems and
      patient samples to provide insights into pathways deregulated in cancer. This
      discovery reveals new biomarkers and therapeutic targets, ultimately stratifying
      patients and informing cohort-based treatment options. Precision medicine
      (molecular profiling of individual tumors combined with established clinical
      pathological parameters) reveals, in real-time, individual patient's diagnostic
      and prognostic risk profile, informing tailored and tumor-specific treatment
      plans. Here we discuss advances in precision medicine presented at the Irish
      Association for Cancer Research Annual Meeting, highlighting examples where
      personalized medicine approaches have led to precision discovery in individual
      tumors, informing customized treatment programs.

PMID- 29068366
TI  - Strengthening the Referral System through Social Capital: A Qualitative Inquiry
      in Ghana.
AB  - The referral system in health care has been noted as very influential in
      determining which services are accessed and when. Nonetheless, existing studies
      have relied on specific measurable factors relating to health personnel,
      transportation and communication infrastructure, and finance to explain the
      challenges facing the referral policy in developing countries. While this is
      understandable, the role of social capital remains mostly uncharted even though
      it is implicit in the well-known lay referral system. Using various facets of the
      social capital concept, this paper empirically examines how the resources
      embedded in both structural and cognitive aspects of social relationships
      influence knowledge of, and adherence to, referral policy. This study is based on
      semi-structured in-depth interviews conducted with 79 adults in the Ashanti
      Region of Ghana in 2015. Of the 79 participants, 28 lived in urban areas and 51
      in rural localities. Eight health personnel and eight community leaders also
      contributed to the study. Additionally, six focus group discussions were held.
      The findings indicated that both cognitive and structural forms of social capital
      considerably underpinned the ability and willingness of people to adhere to the
      referral process. Moreover, the role of social capital was double-barrelled. It
      contributed in a significant way to encouraging or dissuading potential patients
      from rightly embracing the policy. In addition, precepts of social capital
      reinforced both positive and adverse effects of the other determinants of the
      policy such as finance and transportation. However, the magnitude of such impact
      was linked to how 'resourceful' and 'trustworthy' one's available social
      acquaintances were. The paper suggests that a cautious engagement with social
      capital will make it a potentially powerful tool for understanding the gaps in
      and improving the effectiveness of referral policy.

PMID- 29068365
TI  - Interplay of Socioeconomic Status and Supermarket Distance Is Associated with
      Excess Obesity Risk: A UK Cross-Sectional Study.
AB  - U.S. policy initiatives have sought to improve health through attracting
      neighborhood supermarket investment. Little evidence exists to suggest that these
      policies will be effective, in particular where there are socioeconomic barriers
      to healthy eating. We measured the independent associations and combined
      interplay of supermarket access and socioeconomic status with obesity. Using data
      on 9702 UK adults, we employed adjusted regression analyses to estimate measured
      BMI (kg/m2), overweight (25 >= BMI < 30) and obesity (>=30), across participants'
      highest educational attainment (three groups) and tertiles of street network
      distance (km) from home location to nearest supermarket. Jointly-classified
      models estimated combined associations of education and supermarket distance, and
      relative excess risk due to interaction (RERI). Participants farthest away from
      their nearest supermarket had higher odds of obesity (OR 1.33, 95% CI: 1.11,
      1.58), relative to those living closest. Lower education was also associated with
      higher odds of obesity. Those least-educated and living farthest away had 3.39
      (2.46-4.65) times the odds of being obese, compared to those highest-educated and
      living closest, with an excess obesity risk (RERI = 0.09); results were similar
      for overweight. Our results suggest that public health can be improved through
      planning better access to supermarkets, in combination with interventions to
      address socioeconomic barriers.

PMID- 29068367
TI  - Unraveling the Origin of Magnetism in Mesoporous Cu-Doped SnO2 Magnetic
      Semiconductors.
AB  - The origin of magnetism in wide-gap semiconductors doped with non-ferromagnetic
      3d transition metals still remains intriguing. In this article, insights in the
      magnetic properties of ordered mesoporous Cu-doped SnO2 powders, prepared by hard
      templating, have been unraveled. Whereas, both oxygen vacancies and Fe-based
      impurity phases could be a plausible explanation for the observed room
      temperature ferromagnetism, the low temperature magnetism is mainly and
      unambiguously arising from the nanoscale nature of the formed antiferromagnetic
      CuO, which results in a net magnetization that is reminiscent of ferromagnetic
      behavior. This is ascribed to uncompensated spins and shape-mediated spin canting
      effects. The reduced blocking temperature, which resides between 30 and 5 K, and
      traces of vertical shifts in the hysteresis loops confirm size effects in CuO.
      The mesoporous nature of the system with a large surface-to-volume ratio likely
      promotes the occurrence of uncompensated spins, spin canting, and spin
      frustration, offering new prospects in the use of magnetic semiconductors for
      energy-efficient spintronics.

PMID- 29068368
TI  - Turkey National Mesothelioma Surveillance and Environmental Asbestos Exposure
      Control Program.
AB  - Malignant mesothelioma (MM) is an important health problem due to ongoing
      asbestos exposure. Environmental asbestos exposure leads to a high risk of MM in
      Turkey. The Turkish Mesothelioma Working Group and the Turkish Public Health
      Institute designed and performed the Turkey National Mesothelioma Surveillance
      and Environmental Asbestos Exposure Control Program (TUNMES-EAECP). The aim of
      this study was to analyze the results of the TUNMES-EAECP. Patients diagnosed
      with MM (code C45.0-C45.9) between 2008 and 2012 were identified. The "from case
      to the field" method was used to determine the villages with current or previous
      asbestos exposure. Special public health teams took soil samples from these
      villages, which were then examined using an X-ray diffractometer. Direct
      Standardized Average Annual Mesothelioma Incidence Rate (AMIR) and relative risk
      (RR) of MM were calculated. Finally, a projection on the incidence of MM between
      2013 and 2033 was made. The number of confirmed MM cases was 5617 with a male to
      female ratio of 1.36. Mean age was 61.7 +/- 13.4 (20-96) years. The median
      survival was eight (95% CI 7.6-8.4) months. Asbestos exposure continues in 379
      villages, with 158,068 people still living in high risk areas. The standardized
      AMIR was 2.33/100,000 per year. The risk of MM was higher in males, in both sexes
      over the age of 40, in asbestos-containing provinces, and in those where the
      TUNMES was organized. Among the population with continuing asbestos exposure in
      rural areas, the number of MM cases between 2013 and 2033 was estimated as 2511.
      As such, the incidence of MM in Turkey is as high as in industrialized countries.
      Asbestos exposure in rural areas continues to be a serious problem in Turkey,
      which obviates the necessity for effective preventive measures.

PMID- 29068369
TI  - Arrhythmia Evaluation in Wearable ECG Devices.
AB  - This study evaluates four databases from PhysioNet: The American Heart
      Association database (AHADB), Creighton University Ventricular Tachyarrhythmia
      database (CUDB), MIT-BIH Arrhythmia database (MITDB), and MIT-BIH Noise Stress
      Test database (NSTDB). The ANSI/AAMI EC57:2012 is used for the evaluation of the
      algorithms for the supraventricular ectopic beat (SVEB), ventricular ectopic beat
      (VEB), atrial fibrillation (AF), and ventricular fibrillation (VF) via the
      evaluation of the sensitivity, positive predictivity and false positive rate.
      Sample entropy, fast Fourier transform (FFT), and multilayer perceptron neural
      network with backpropagation training algorithm are selected for the integrated
      detection algorithms. For this study, the result for SVEB has some improvements
      compared to a previous study that also utilized ANSI/AAMI EC57. In further, VEB
      sensitivity and positive predictivity gross evaluations have greater than 80%,
      except for the positive predictivity of the NSTDB database. For AF gross
      evaluation of MITDB database, the results show very good classification,
      excluding the episode sensitivity. In advanced, for VF gross evaluation, the
      episode sensitivity and positive predictivity for the AHADB, MITDB, and CUDB,
      have greater than 80%, except for MITDB episode positive predictivity, which is
      75%. The achieved results show that the proposed integrated SVEB, VEB, AF, and VF
      detection algorithm has an accurate classification according to ANSI/AAMI
      EC57:2012. In conclusion, the proposed integrated detection algorithm can achieve
      good accuracy in comparison with other previous studies. Furthermore, more
      advanced algorithms and hardware devices should be performed in future for
      arrhythmia detection and evaluation.

PMID- 29068371
TI  - Map Sensitivity vs. Map Dependency: A Case Study of Subway Maps' Impact on
      Passenger Route Choices in Washington DC.
AB  - This paper addresses the key assumption in behavioral and transportation planning
      literature that, when people use a transit system more frequently, they become
      less dependent on and less sensitive to transit maps in their decision-making.
      Therefore, according to this assumption, map changes are much less impactful to
      travel decisions of frequent riders than to that of first-time or new passengers.
      This assumption-though never empirically validated-has been the major hurdle for
      transit maps to becoming a planning tool to change passengers' behavior. This
      paper examines this assumption using the Washington DC metro map as a case study
      by conducting a route choice experiment between 30 Origin-Destination (O-D) pairs
      on seven metro map designs. The experiment targets two types of passengers:
      frequent metro riders through advertisements on a free daily newspaper available
      at DC metro stations, and general residents in the Washington metropolitan area
      through Amazon Mechanical Turk, an online crowdsourcing platform. A total of 255
      and 371 participants made 2024 and 2960 route choices in the respective
      experiments. The results show that frequent passengers are in fact more sensitive
      to subtle changes in map design than general residents who are less likely to be
      familiar with the metro map and therefore unaffected by map changes presented in
      the alternative designs. The work disproves the aforementioned assumption and
      further validates metro maps as an effective planning tool in transit systems.

PMID- 29068370
TI  - RNA-Seq Analysis of Plant Maturity in Crested Wheatgrass (Agropyron cristatum
      L.).
AB  - Crested wheatgrass (Agropyron cristatum L.) breeding programs aim to develop
      later maturing cultivars for extending early spring grazing in Western Canada.
      Plant maturity is a complex genetic trait, and little is known about genes
      associated with late maturity in this species. An attempt was made using RNA-Seq
      to profile the transcriptome of crested wheatgrass maturity and to analyze
      differentially expressed genes (DEGs) between early and late maturing lines.
      Three cDNA libraries for each line were generated by sampling leaves at the stem
      elongation stage, spikes at the boot and anthesis stages. A total of 75,218,230
      and 74,015,092 clean sequence reads were obtained for early and late maturing
      lines, respectively. De novo assembly of all sequence reads generated 401,587
      transcripts with a mean length of 546 bp and N50 length of 691 bp. Out of 13,133
      DEGs detected, 22, 17, and eight flowering related DEGs were identified for the
      three stages, respectively. Twelve DEGs, including nine flowering related DEGs at
      the stem elongation stage were further confirmed by qRT-PCR. The analysis of
      homologous genes of the photoperiod pathway revealed their lower expression in
      the late maturing line at the stem elongation stage, suggesting that their
      differential expression contributed to late maturity in crested wheatgrass.

PMID- 29068372
TI  - Deep Sequencing Data and Infectivity Assays Indicate that Chickpea Chlorotic
      Dwarf Virus is the Etiological Agent of the "Hard Fruit Syndrome" of Watermelon.
AB  - Chickpea chlorotic dwarf virus (CpCDV), a polyphagous mastrevirus, family
      Geminiviridae, has been recently linked to the onset of the "hard fruit syndrome"
      of watermelon, first described in Tunisia, that makes fruits unmarketable due to
      the presence of white hard portions in the flesh, chlorotic mottling on the rind,
      and an unpleasant taste. To investigate the etiological agent of this disease,
      total RNA extracted from symptomatic watermelon fruits was subjected to small RNA
      sequencing through next generation sequencing (NGS) techniques. Data obtained
      showed the presence of CpCDV and two other viral species. However, following
      validation through polymerase chain reaction (PCR), CpCDV was the only viral
      species consistently detected in all samples. Watermelon seedlings were then
      challenged by an agroinfectious CpCDV clone; several plants proved to be CpCDV
      infected, and were able to produce fruits. CpCDV infected and replicated in
      watermelon fruits and leaves, leading to abnormality in fruits and in seed
      production, similar to those described in field. These results indicate that
      CpCDV is the etiological agent of the "hard fruit syndrome" of watermelon.

PMID- 29068373
TI  - A Search for Dual Action HIV-1 Reverse Transcriptase, Bacterial RNA Polymerase
      Inhibitors.
AB  - Using molecular modeling approach, potential antibacterial agents with triazole
      core were proposed. A moderate to weak level of antibacterial activity in most of
      the compounds have been observed, with best minimal inhibitory concentration
      (MIC) value of 0.003 mg/mL, as shown by the 15 against S. epidermidis. Studied
      compounds were also submitted to the antifungal assay. The best antifungal
      activity was detected for 16 with MIC at 0.125 and 0.25 mg/mL against C. albicans
      and C. parapsilosis, respectively.

PMID- 29068374
TI  - Ameliorative Effect of Caffeic Acid on Capecitabine-Induced Hepatic and Renal
      Dysfunction: Involvement of the Antioxidant Defence System.
AB  - Background: It has been postulated that during liver and kidney damage there is a
      decreased in the antioxidant status associated with a simultaneous increase in
      the reactive oxygen species and lipid peroxidation. In consonant with this,
      Capecitabine, an oral chemotherapy and inactive non-cytotoxic fluoropyrimidine
      considered for the treatment of advance colorectal cancer, has also been shown to
      induce oxidative stress in liver tissues. Caffeic acid, a typical
      hydroxycinnamic, has been claimed to be effective against oxidative stress.
      Therefore, this present work studied the protective effect of caffeic acid on
      oxidative stress-induced liver and kidney damage by the administration of
      capecitabine. Methods: Twenty-four male Wistar strain rats were randomly divided
      into four treatment groups: A. control, B. capecitabine (CPTB)-treated group (30
      mg/kg b.w. CPTB), C. caffeic acid (CFA)-treated group (100 mg/kg b.w. CFA) and D.
      co-treated group with CFA (100 mg/kg b.w.) and CPTB (30 mg/kg b.w.). Results:
      Caffeic acid administration significantly ameliorated the elevated plasma
      biomarkers of hepatic and renal tissue damage induced by the capecitabine and
      improved enzymatic and non-enzymatic antioxidant levels in liver organ.
      Conclusions: The protective effect of caffeic acid could be attributed to its
      ability to boost the antioxidant defence system and reduce lipid peroxidation.

PMID- 29068375
TI  - Recent Progress in Optical Biosensors Based on Smartphone Platforms.
AB  - With a rapid improvement of smartphone hardware and software, especially
      complementary metal oxide semiconductor (CMOS) cameras, many optical biosensors
      based on smartphone platforms have been presented, which have pushed the
      development of the point-of-care testing (POCT). Imaging-based and spectrometry
      based detection techniques have been widely explored via different approaches.
      Combined with the smartphone, imaging-based and spectrometry-based methods are
      currently used to investigate a wide range of molecular properties in chemical
      and biological science for biosensing and diagnostics. Imaging techniques based
      on smartphone-based microscopes are utilized to capture microscale analysts,
      while spectrometry-based techniques are used to probe reactions or changes of
      molecules. Here, we critically review the most recent progress in imaging-based
      and spectrometry-based smartphone-integrated platforms that have been developed
      for chemical experiments and biological diagnosis. We focus on the analytical
      performance and the complexity for implementation of the platforms.

PMID- 29068377
TI  - Interdisciplinary eHealth Practice in Cancer Care: A Review of the Literature.
AB  - This review aimed to identify research that described how eHealth facilitates
      interdisciplinary cancer care and to understand the ways in which eHealth
      innovations are being used in this setting. An integrative review of eHealth
      interventions used for interdisciplinary care for people with cancer was
      conducted by systematically searching research databases in March 2015, and
      repeated in September 2016. Searches resulted in 8531 citations, of which 140
      were retrieved and scanned in full, with twenty-six studies included in the
      review. Analysis of data extracted from the included articles revealed five broad
      themes: (i) data collection and accessibility; (ii) virtual multidisciplinary
      teams; (iii) communication between individuals involved in the delivery of health
      services; (iv) communication pathways between patients and cancer care teams; and
      (v) health professional-led change. Use of eHealth interventions in cancer care
      was widespread, particularly to support interdisciplinary care. However, research
      has focused on development and implementation of interventions, rather than on
      long-term impact. Further research is warranted to explore design, evaluation,
      and long-term sustainability of eHealth systems and interventions in
      interdisciplinary cancer care. Technology evolves quickly and researchers need to
      provide health professionals with timely guidance on how best to respond to new
      technologies in the health sector.

PMID- 29068376
TI  - A Mini-Review on the Effect of Docosahexaenoic Acid (DHA) on Cerulein-Induced and
      Hypertriglyceridemic Acute Pancreatitis.
AB  - Acute pancreatitis refers to the sudden inflammation of the pancreas. It is
      associated with premature activation and release of digestive enzymes into the
      pancreatic interstitium and systemic circulation, resulting in pancreatic tissue
      autodigestion and multiple organ dysfunction, as well as with increased cytokine
      production, ultimately leading to deleterious local and systemic effects.
      Although mechanisms involved in pathogenesis of acute pancreatitis have not been
      completely elucidated, oxidative stress is regarded as a major risk factor. In
      human acute pancreatitis, lipid peroxide levels in pancreatic tissues increase.
      Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (C22:6n-3),
      exerts anti-inflammatory and antioxidant effects on various cells. Previous
      studies have shown that DHA activates peroxisome proliferator-activated receptor
      gamma and induces catalase, which inhibits oxidative stress-mediated inflammatory
      signaling required for cytokine expression in experimental acute pancreatitis
      using cerulein. Cerulein, a cholecystokinin analog, induces intra-acinar
      activation of trypsinogen in the pancreas, which results in human acute
      pancreatitis-like symptoms. Therefore, DHA supplementation may be beneficial for
      preventing or inhibiting acute pancreatitis development. Since DHA reduces serum
      triglyceride levels, addition of DHA to lipid-lowering drugs like statins has
      been investigated to reduce hypertriglyceridemic acute pancreatitis. However,
      high DHA concentrations increase cytosolic Ca2+, which activates protein kinase C
      and may induce hyperlipidemic acute pancreatitis. In this review, effect of DHA
      on cerulein-induced and hypertriglyceridemic acute pancreatitis has been
      discussed. The relation of high concentration of DHA to hyperlipidemic acute
      pancreatitis has been included.

PMID- 29068379
TI  - Financing Cocaine Use in a Homeless Population.
AB  - Background: Cocaine use is highly prevalent among homeless populations, yet
      little is known about how it is financed. This study examined associations of
      income sources with cocaine use and financing of drugs in a longitudinal
      evaluation of a homeless sample. Methods: A homeless sample was recruited
      systematically in St. Louis in 1999-2001 and longitudinally assessed annually
      over two years using the Diagnostic Interview Schedule and the Homeless
      Supplement, with urine drug testing. Results: More than half (55%) of
      participants with complete follow-up data (N = 255/400) had current year cocaine
      use. Current users spent nearly $400 (half their income) in the last month on
      drugs at baseline. Benefits, welfare, and disability were negatively associated
      and employment and income from family/friends, panhandling, and other illegal
      activities were positively associated with cocaine use and monetary expenditures
      for cocaine. Conclusions: Findings suggest that illegal and informal income
      generating activities are primary sources for immediate gratification with
      cocaine use and public entitlements do not appear to be primary funding sources
      used by homeless populations. Policy linking drug testing to benefits is likely
      to have little utility, and public expenditures on measures to unlink drug use
      and income might be more effectively used to fund employment and treatment
      programs.

PMID- 29068378
TI  - Primary and Immortalized Human Respiratory Cells Display Different Patterns of
      Cytotoxicity and Cytokine Release upon Exposure to Deoxynivalenol, Nivalenol and
      Fusarenon-X.
AB  - The type B trichothecene mycotoxins deoxynivalenol (DON), nivalenol (NIV) and
      fusarenon-X (FX) are structurally related secondary metabolites frequently
      produced by Fusarium on wheat. Consequently, DON, NIV and FX contaminate wheat
      dusts, exposing grain workers to toxins by inhalation. Those trichothecenes at
      low, relevant, exposition concentrations have differential effects on intestinal
      cells, but whether such differences exist with respiratory cells is mostly
      unknown, while it is required to assess the combined risk of exposure to
      mycotoxins. The goal of the present study was to compare the effects of DON, NIV
      and FX alone or in combination on the viability and IL-6 and IL-8-inducing
      capacity of human epithelial cells representative of the respiratory tract:
      primary human airway epithelial cells of nasal (hAECN) and bronchial (hAECB)
      origin, and immortalized human bronchial (16HBE14o-) and alveolar (A549)
      epithelial cell lines. We report that A549 cells are particularly resistant to
      the cytotoxic effects of mycotoxins. FX is more toxic than DON and NIV for all
      epithelial cell types. Nasal and bronchial primary cells are more sensitive than
      bronchial and alveolar cell lines to combined mycotoxin mixtures at low
      concentrations, although they are less sensitive to mycotoxins alone.
      Interactions between mycotoxins at low concentrations are rarely additive and are
      observed only for DON/NIV and NIV/FX on hAECB cells and DON/NIV/FX on A549 cells.
      Most interactions at low mycotoxin concentrations are synergistic, antagonistic
      interactions being observed only for DON/FX on hAECB, DON/NIV on 16HBE14o- and
      NIV/FX on A549 cells. DON, NIV and FX induce, albeit at different levels, IL-6
      and IL-8 release by all cell types. However, NIV and FX at concentrations of low
      cytotoxicity induce IL-6 release by hAECB and A549 cells, and IL-8 release by
      hAECN cells. Overall, these data suggest that combined exposure to mycotoxins at
      low concentrations have a stronger effect on primary nasal epithelial cells than
      on bronchial epithelial cells and activate different inflammatory pathways. This
      information is particularly relevant for future studies about the hazard of
      occupational exposure to mycotoxins by inhalation and its impact on the
      respiratory tract.

PMID- 29068382
TI  - A Study of The Effect of Demand Uncertainty for Low-Carbon Products Using a
      Newsvendor Model.
AB  - This paper studies the effect of uncertain demand on a low-carbon product by
      using a newsvendor model. With two different kinds of market scales, we examine a
      game whereby a manufacturer produces and delivers a single new low-carbon product
      to a single retailer. The retailer observes the demand information and gives an
      order before the selling season. We find in the game that if the retailer shares
      truthful (or in contrast unreal or even does not share) forecast information with
      the manufacturer, the manufacturer will give a low (high) wholesale price through
      the sequence of events. In addition, as a policy-maker, the government posts a
      subsidy by selling the low-carbon product per unit. The manufacturer creates a
      new contract with a rebate for the retailer. We also take the consumer aversion
      coefficient and truth coefficient as qualitative variables into our model to
      study the order, pricing, and expected profit for the members of supply chain.
      The research shows that uncertain demand causes a the major effect on the new low
      carbon product. Thereby, we suggest the retailer should share more truthful
      information with the manufacturer.

PMID- 29068381
TI  - Investigation of Non-Covalent Interactions of Aflatoxins (B1, B2, G1, G2, and M1)
      with Serum Albumin.
AB  - Aflatoxins are widely spread mycotoxins produced mainly by Aspergillus species.
      Consumption of aflatoxin-contaminated foods and drinks causes serious health
      risks for people worldwide. It is well-known that the reactive epoxide metabolite
      of aflatoxin B1 (AFB1) forms covalent adducts with serum albumin. However, non
      covalent interactions of aflatoxins with human serum albumin (HSA) are poorly
      characterized. Thus, in this study the complex formation of aflatoxins was
      examined with HSA applying spectroscopic and molecular modelling studies. Our
      results demonstrate that aflatoxins form stable complexes with HSA as reflected
      by binding constants between 2.1 * 104 and 4.5 * 104 dm3/mol. A binding free
      energy value of -26.90 kJ mol-1 suggests a spontaneous binding process between
      AFB1 and HSA at room-temperature, while the positive entropy change of 55.1 JK-1
      mol-1 indicates a partial decomposition of the solvation shells of the
      interacting molecules. Modeling studies and investigations with site markers
      suggest that Sudlow's Site I of subdomain IIA is the high affinity binding site
      of aflatoxins on HSA. Interaction of AFB1 with bovine, porcine, and rat serum
      albumins was also investigated. Similar stabilities of the examined AFB1-albumin
      complexes were observed suggesting the low species differences of the albumin
      binding of aflatoxins.

PMID- 29068383
TI  - Synthesis, Structure, Surface and Antimicrobial Properties of New Oligomeric
      Quaternary Ammonium Salts with Aromatic Spacers.
AB  - New dimeric, trimeric and tetrameric quaternary ammonium salts were accomplished
      by reaction of tertiary alkyldimethyl amines with appropriate bromomethylbenzene
      derivatives. A series of new cationic surfactants contain different alkyl chain
      lengths (C4-C18), aromatic spacers and different numbers of quaternary nitrogen
      atoms. The structure of the products was confirmed by spectral analysis (FT-IR,
      1H-NMR, 13C-NMR and 2D-NMR), mass spectroscopy (ESI-MS), elemental analysis, as
      well as PM5 semiempirical methods. Compound (21) was also analyzed using X-ray
      crystallography. Critical micelle concentration (CMC) of 1,4-bis-[N-(1-alkyl)-N,N
      dimethylammoniummethyl]benzene dibromides (3-9) was determined to characterize
      the aggregation behavior. The antimicrobial properties of novel QACs (Quaternary
      Ammonium Salts) were examined to set their minimal inhibitory concentration (MIC)
      values against fungi Aspergillus niger, Candida albicans, Penicillium chrysogenum
      and bacteria Staphylococcus aureus, Bacillus subtilis, Escherichia coli and
      Pseudomonas aeruginosa.

PMID- 29068380
TI  - Shiga Toxin Glycosphingolipid Receptors in Human Caco-2 and HCT-8 Colon
      Epithelial Cell Lines.
AB  - Shiga toxins (Stxs) released by enterohemorrhagic Escherichia coli (EHEC) into
      the human colon are the causative agents for fatal outcome of EHEC infections.
      Colon epithelial Caco-2 and HCT-8 cells are widely used for investigating Stx
      mediated intestinal cytotoxicity. Only limited data are available regarding
      precise structures of their Stx receptor glycosphingolipids (GSLs)
      globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), and lipid
      raft association. In this study we identified Gb3Cer and Gb4Cer lipoforms of
      serum-free cultivated Caco-2 and HCT-8 cells, chiefly harboring ceramide moieties
      composed of sphingosine (d18:1) and C16:0, C22:0 or C24:0/C24:1 fatty acid. The
      most significant difference between the two cell lines was the prevalence of
      Gb3Cer with C16 fatty acid in HCT-8 and Gb4Cer with C22-C24 fatty acids in Caco-2
      cells. Lipid compositional analysis of detergent-resistant membranes (DRMs),
      which were used as lipid raft-equivalents, indicated slightly higher relative
      content of Stx receptor Gb3Cer in DRMs of HCT-8 cells when compared to Caco-2
      cells. Cytotoxicity assays revealed substantial sensitivity towards Stx2a for
      both cell lines, evidencing little higher susceptibility of Caco-2 cells versus
      HCT-8 cells. Collectively, Caco-2 and HCT-8 cells express a plethora of different
      receptor lipoforms and are susceptible towards Stx2a exhibiting somewhat lower
      sensitivity when compared to Vero cells.

PMID- 29068385
TI  - Solution Based Methods for the Fabrication of Carbon Nanotube Modified Atomic
      Force Microscopy Probes.
AB  - High aspect ratio carbon nanotubes are ideal candidates to improve the resolution
      and lifetime of atomic force microscopy (AFM) probes. Here, we present simple
      methods for the preparation of carbon nanotube modified AFM probes utilising
      solvent evaporation or dielectrophoresis. Scanning electron microscopy (SEM) of
      the modified probes shows that the carbon nanotubes attach to the probe apex as
      fibres and display a high aspect ratio. Many of the probes made in this manner
      were initially found to exhibit anomalous feedback characteristics during
      scanning, which rendered them unsuitable for imaging. However, we further
      developed and demonstrated a simple method to stabilise the carbon nanotube
      fibres by scanning with high force in tapping mode, which either shortens or
      straightens the carbon fibre, resulting in stable and high quality imaging AFM
      imaging.

PMID- 29068384
TI  - Shiga Toxin-A Model for Glycolipid-Dependent and Lectin-Driven Endocytosis.
AB  - The cellular entry of the bacterial Shiga toxin and the related verotoxins has
      been scrutinized in quite some detail. This is due to their importance as a
      threat to human health. At the same time, the study of Shiga toxin has allowed
      the discovery of novel molecular mechanisms that also apply to the intracellular
      trafficking of endogenous proteins at the plasma membrane and in the endosomal
      system. In this review, the individual steps that lead to Shiga toxin uptake into
      cells will first be presented from a purely mechanistic perspective. Membrane
      biological concepts will be highlighted that are often still poorly explored,
      such as fluctuation force-driven clustering, clathrin-independent membrane
      curvature generation, friction-driven scission, and retrograde sorting on early
      endosomes. It will then be explored whether and how these also apply to other
      pathogens, pathogenic factors, and cellular proteins. The molecular nature of
      Shiga toxin as a carbohydrate-binding protein and that of its cellular receptor
      as a glycosylated raft lipid will be an underlying theme in this discussion. It
      will thereby be illustrated how the study of Shiga toxin has led to the proposal
      of the GlycoLipid-Lectin (GL-Lect) hypothesis on the generation of endocytic pits
      in processes of clathrin-independent endocytosis.

PMID- 29068388
TI  - Reply to the Letter of Terracini B. et al. "Comment on Piscitelli et al.
      Hospitalizations in Pediatric and Adult Patients for All Cancer Type in Italy:
      The EPIKIT Study under the E.U. COHEIRS Project on Environment and Health". Int.
      J. Environ. Res. Public Health 2017, 14, 495.
AB  - A letter to the IJERPH Editor was submitted by Terracini B. et al. as a comment
      to our latest paper "Hospitalizations in Pediatric and Adult Patients for all
      Cancer Type in Italy:[...].

PMID- 29068386
TI  - How Next-Generation Sequencing Has Aided Our Understanding of the Sequence
      Composition and Origin of B Chromosomes.
AB  - Accessory, supernumerary, or-most simply-B chromosomes, are found in many
      eukaryotic karyotypes. These small chromosomes do not follow the usual pattern of
      segregation, but rather are transmitted in a higher than expected frequency. As
      increasingly being demonstrated by next-generation sequencing (NGS), their
      structure comprises fragments of standard (A) chromosomes, although in some plant
      species, their sequence also includes contributions from organellar genomes.
      Transcriptomic analyses of various animal and plant species have revealed that,
      contrary to what used to be the common belief, some of the B chromosome DNA is
      protein-encoding. This review summarizes the progress in understanding B
      chromosome biology enabled by the application of next-generation sequencing
      technology and state-of-the-art bioinformatics. In particular, a contrast is
      drawn between a direct sequencing approach and a strategy based on a comparative
      genomics as alternative routes that can be taken towards the identification of B
      chromosome sequences.

PMID- 29068389
TI  - Clinical Effect of IRT-5 Probiotics on Immune Modulation of Autoimmunity or
      Alloimmunity in the Eye.
AB  - BACKGROUND: Although the relation of the gut microbiota to a development of
      autoimmune and inflammatory diseases has been investigated in various animal
      models, there are limited studies that evaluate the effect of probiotics in the
      autoimmune eye disease. Therefore, we aimed to investigate the effect of IRT-5
      probiotics consisting of Lactobacillus casei, Lactobacillus acidophilus,
      Lactobacillus reuteri, Bifidobacterium bifidum, and Streptococcus thermophilus on
      the autoimmunity of uveitis and dry eye and alloimmunity of corneal
      transplantation. METHODS: Experimental autoimmune uveitis was induced by
      subcutaneous immunization with interphotoreceptor-binding protein and
      intraperitoneal injection of pertussis toxin in C57BL/6 (B6) mice. For an
      autoimmune dry eye model, 12-weeks-old NOD.B10.H2b mice were used. Donor cornea
      of B6 mice was transplanted into BALB/C mice. IRT-5 probiotics or phosphate
      buffered saline (PBS) were administered for three weeks immediately after
      induction of uveitis or transplantation. The inflammation score of the retinal
      tissues, dry eye manifestations (corneal staining and tear secretion), and graft
      survival were measured in each model. The changes of T cells were evaluated in
      drainage lymph nodes using fluorescence-activated cell sorting. RESULTS: Retinal
      histology score in IRT-5 group of uveitis was lower than that in PBS group (p =
      0.045). Ocular staining score was lower (p < 0.0001) and tear secretion was
      higher (p < 0.0001) in the IRT-5 group of NOD.B10.H2b mice than that in the PBS
      group. However, the graft survival in the IRT-5 group was not different from
      those of PBS group. The percentage of regulatory T cells was increased in the IRT
      5-treated dry eye models (p = 0.032). The percentage of CD8+IL-17hi (p = 0.027)
      and CD8+ interferon gamma (IFNgamma)hi cells (p = 0.022) were significantly
      decreased in the IRT-5-treated uveitis models and the percentage of
      CD8+IFNgammahi cells was markedly reduced (p = 0.036) in IRT-5-treated dry eye
      model. CONCLUSION: Our results suggest that administration of IRT-5 probiotics
      may modulate clinical manifestations of autoimmunity in the eye, but not on
      alloimmunity of corneal transplantation.

PMID- 29068392
TI  - Linear Extended State Observer-Based Motion Synchronization Control for Hybrid
      Actuation System of More Electric Aircraft.
AB  - Moving towards the more electric aircraft (MEA), a hybrid actuator configuration
      provides an opportunity to introduce electromechanical actuator (EMA) into
      primary flight control. In the hybrid actuation system (HAS), an electro
      hydraulic servo actuator (EHSA) and an EMA operate on the same control surface.
      In order to solve force fighting problem in HAS, this paper proposes a novel
      linear extended state observer (LESO)-based motion synchronization control
      method. To cope with the problem of unavailability of the state signals required
      by the motion synchronization controller, LESO is designed for EHSA and EMA to
      observe the state variables. Based on the observed states of LESO, motion
      synchronization controllers could enable EHSA and EMA to simultaneously track the
      desired motion trajectories. Additionally, nonlinearities, uncertainties and
      unknown disturbances as well as the coupling term between EHSA and EMA can be
      estimated and compensated by using the extended state of the proposed LESO.
      Finally, comparative simulation results indicate that the proposed LESO-based
      motion synchronization controller could reduce significant force fighting between
      EHSA and EMA.

PMID- 29068387
TI  - Bioactivity of Olive Oil Phenols in Neuroprotection.
AB  - Neurological disorders such as stroke, Alzheimer's and Parkinson's diseases are
      associated with high morbidity and mortality, and few or no effective options are
      available for their treatment. These disorders share common pathological
      characteristics like the induction of oxidative stress, abnormal protein
      aggregation, perturbed Ca2+ homeostasis, excitotoxicity, inflammation and
      apoptosis. A large body of evidence supports the beneficial effects of the
      Mediterranean diet in preventing neurodegeneration. As the Mediterranean diet is
      characterized by a high consumption of extra-virgin olive oil it has been
      hypothesized that olive oil, and in particular its phenols, could be responsible
      for the beneficial effect of the Mediterranean diet. This review provides an
      updated vision of the beneficial properties of olive oil and olive oil phenols in
      preventing/counteracting both acute and chronic neurodegenerative diseases.

PMID- 29068391
TI  - Synthesis and Radioprotective Activity of Mitochondria Targeted Dihydropyridines
      In Vitro.
AB  - The radiation-induced damage to mitochondrial oxidative respiratory chain could
      lead to generating of superoxide anions (O2-) and secondary reactive oxygen
      species (ROS), which are the major resources of continuous ROS production after
      radiation. Scavenging radiation-induced ROS effectively can help mitochondria to
      maintain their physiological function and relief cells from oxidative stress.
      Dihydropyridines (DHPs) are biomimetic hydrogen sources that could protect cells
      against radiation damage. In this study, we designed and synthetized three novel
      mitochondrial-targeted dihydropyridines (Mito-DHPs) that utilize the
      mitochondrial membrane potential to enter the organelle and scavenge ROS.
      MitoTracker confirmed Mito-DHPs accumulation in mitochondria, and the DCFH-DA
      assay demonstrated effective ROS scavenging activity. In addition, the gamma-H2AX
      and comet assay demonstrated the ability of Mito-DHPs to protect against both
      radiation and ROS-induced DNA strand breaks. Furthermore, Mito-DHP1 proved to be
      non-toxic and displayed significant radioprotection activity (p < 0.05) in vitro.
      Mito-DHPs are therefore promising antioxidants that could penetrate the membrane
      of mitochondria, scavenge excessive ROS, and protect cells against radiation
      induced oxidative damage.

PMID- 29068390
TI  - Does Hypoxia Cause Carcinogenic Iron Accumulation in Alcoholic Liver Disease
      (ALD)?
AB  - Alcoholic liver disease (ALD) is a leading health risk worldwide. Hepatic iron
      overload is frequently observed in ALD patients and it is an important and
      independent factor for disease progression, survival, and the development of
      primary liver cancer (HCC). At a systemic level, iron homeostasis is controlled
      by the liver-secreted hormone hepcidin. Hepcidin regulation is complex and still
      not completely understood. It is modulated by many pathophysiological conditions
      associated with ALD, such as inflammation, anemia, oxidative stress/H2O2, or
      hypoxia. Namely, the data on hypoxia-signaling of hepcidin are conflicting, which
      seems to be mainly due to interpretational limitations of in vivo data and
      methodological challenges. Hence, it is often overlooked that hepcidin-secreting
      hepatocytes are physiologically exposed to 2-7% oxygen, and that key oxygen
      species such as H2O2 act as signaling messengers in such a hypoxic environment.
      Indeed, with the recently introduced glucose oxidase/catalase (GOX/CAT) system it
      has been possible to independently study hypoxia and H2O2 signaling. First
      preliminary data indicate that hypoxia enhances H2O2-mediated induction of
      hepcidin, pointing towards oxidases such as NADPH oxidase 4 (NOX4). We here
      review and discuss novel concepts of hypoxia signaling that could help to better
      understand hepcidin-associated iron overload in ALD.

PMID- 29068393
TI  - Fatal Pediatric Motor Vehicle Crashes on U.S. Native American Indian Lands
      Compared to Adjacent Non-Indian Lands: Restraint Use and Injury by Driver,
      Vehicle, Roadway and Crash Characteristics.
AB  - There are large disparities in American Indian pediatric motor vehicle (MV)
      mortality with reports that several factors may contribute. The Fatality Analysis
      Reporting System for 2000-2014 was used to examine restraint use for occupants
      aged 0-19 years involved in fatal MV crashes on Indian lands (n = 1667) and non
      Indian lands in adjacent states (n = 126,080). SAS GLIMMIX logistic regression
      with random effects was used to generate odds ratios (OR) with 95% confidence
      intervals (CI). Restraint use increased in both areas over the study period with
      restraint use on Indian lands being just over half that of non-Indian lands for
      drivers (36.8% vs. 67.8%, p < 0.0001) and for pediatric passengers (33.1% vs.
      59.3%, p < 0.0001). Driver restraint was the strongest predictor of passenger
      restraint on both Indian and non-Indian lands exerting a stronger effect in ages
      13-19 than in 0-12 year olds. Valid licensed driver was a significant predictor
      of restraint use in ages 0-12 years. Passengers in non-cars (SUVs, vans and
      pickup trucks) were less likely to be restrained. Restraint use improved over the
      study period in both areas, but disparities failed to narrow as restraint use
      remains lower and driver, vehicle and crash risk factors higher for MV mortality
      on Indian lands.

PMID- 29068394
TI  - Hepatotoxicity Induced by Sophora flavescens and Hepatic Accumulation of
      Kurarinone, a Major Hepatotoxic Constituent of Sophora flavescens in Rats.
AB  - Our previous study showed that kurarinone was the main hepatotoxic ingredient of
      Sophora flavescens, accumulating in the liver. This study characterized the
      mechanism of Sophora flavescens extract (ESF) hepatotoxicity and hepatic
      accumulation of kurarinone. ESF impaired hepatic function and caused fat
      accumulation in the liver after oral administration (1.25 and 2.5 g/kg for 14
      days in rats). Serum metabolomics evaluation based on high-resolution mass
      spectrometry was conducted and real-time PCR was used to determine the expression
      levels of CPT-1, CPT-2, PPAR-alpha, and LCAD genes. Effects of kurarinone on
      triglyceride levels were evaluated in HL-7702 cells. Tissue distribution of
      kurarinone and kurarinone glucuronides was analyzed in rats receiving ESF (2.5
      g/kg). Active uptake of kurarinone and kurarinone glucuronides was studied in
      OAT2-, OATP1B1-, OATP2B1-, and OATP1B3-transfected HEK293 cells. Our results
      revealed that after oral administration of ESF in rats, kurarinone glucuronides
      were actively transported into hepatocytes by OATP1B3 and hydrolyzed into
      kurarinone, which inhibited fatty acid beta-oxidation through the reduction of l
      carnitine and the inhibition of PPAR-alpha pathway, ultimately leading to lipid
      accumulation and liver injury. These findings contribute to understanding
      hepatotoxicity of kurarinone after oral administration of ESF.

PMID- 29068395
TI  - Analyzing and Modelling the Corrosion Behavior of Ni/Al2O3, Ni/SiC, Ni/ZrO2 and
      Ni/Graphene Nanocomposite Coatings.
AB  - A study has been presented on the effects of intrinsic mechanical parameters,
      such as surface stress, surface elastic modulus, surface porosity, permeability
      and grain size on the corrosion failure of nanocomposite coatings. A set of
      mechano-electrochemical equations was developed by combining the popular Butler
      Volmer and Duhem expressions to analyze the direct influence of mechanical
      parameters on the electrochemical reactions in nanocomposite coatings.
      Nanocomposite coatings of Ni with Al2O3, SiC, ZrO2 and Graphene nanoparticles
      were studied as examples. The predictions showed that the corrosion rate of the
      nanocoatings increased with increasing grain size due to increase in surface
      stress, surface porosity and permeability of nanocoatings. A detailed
      experimental study was performed in which the nanocomposite coatings were
      subjected to an accelerated corrosion testing. The experimental results helped to
      develop and validate the equations by qualitative comparison between the
      experimental and predicted results showing good agreement between the two.

PMID- 29068396
TI  - Comparative Analysis of the Cytology and Transcriptomes of the Cytoplasmic Male
      Sterility Line H276A and Its Maintainer Line H276B of Cotton (Gossypium
      barbadense L.).
AB  - In this study, the tetrad stage of microspore development in a new cotton
      (Gossypium barbadense L.) cytoplasmic male sterility (CMS) line, H276A, was
      identified using paraffin sections at the abortion stage. To explore the
      molecular mechanism underlying CMS in cotton, a comparative transcriptome
      analysis between the CMS line H276A and its maintainer line H276B at the tetrad
      stage was conducted using an Illumina HiSeq 4000 platform. The comparison of
      H276A with H276B revealed a total of 64,675 genes, which consisted of 59,255
      known and 5420 novel genes. An analysis of the two libraries with a given
      threshold yielded a total of 3603 differentially expressed genes (DEGs), which
      included 1363 up- and 2240 down-regulated genes. Gene Ontology (GO) annotation
      showed that 2171 DEGs were distributed into 38 categories, and a Kyoto
      Encyclopedia of Genes and Genomes (KEGG) analysis showed that 2683 DEGs were
      classified into 127 groups. Thirteen DEGs were randomly selected and detected by
      quantitative reverse-transcribed PCR (qRT-PCR), and the results indicated that
      the transcriptome sequencing results were reliable. The bioinformatic analysis
      results in conjunction with previously reported data revealed key DEGs that might
      be associated with the male sterility features of H276A. Our results provide a
      comprehensive foundation for understanding anther development and will accelerate
      the study of the molecular mechanisms of CMS in cotton.

PMID- 29068397
TI  - Diet Quality Associated with Total Sodium Intake among US Adults Aged >=18 Years
      National Health and Nutrition Examination Survey, 2009-2012.
AB  - Diet quality or macronutrient composition of total daily sodium intake (dNa)
      <2300 mg/day in the United States (US) is unknown. Using data from 2011-2014
      NHANES (National Health and Nutrition Examination Survey), we examined 24-h
      dietary recalls (n = 10,142) from adults aged >=18 years and investigated how
      diet composition and quality are associated with dNa. Diet quality was assessed
      using components of macronutrients and Healthy Eating Index 2010 (HEI-2010).
      Associations were tested using linear regression analysis adjusted for total
      energy (kcal), age, gender, and race/ethnicity. One-day dNa in the lower
      quartiles were more likely reported among women, older adults (>=65 years old),
      and lower quartiles of total energy (kcal) (p-values <= 0.001). With increasing
      dNa, there was an increase in the mean protein, fiber, and total fat densities,
      while total carbohydrates densities decreased. As dNa increased, meat protein,
      refined grains, dairy, and total vegetables, greens and beans densities
      increased; while total fruit and whole fruit densities decreased. Modified HEI
      2010 total score (total score without sodium component) increased as dNa
      increased (adjusted coefficient: 0.11, 95% confidence interval = 0.07, 0.15).
      Although diet quality, based on modified HEI-2010 total score, increased on days
      with greater dNa, there is much room for improvement with mean diet quality of
      about half of the optimal level.

PMID- 29068399
TI  - Major Differences in Diet across Three Linguistic Regions of Switzerland: Results
      from the First National Nutrition Survey menuCH.
AB  - Switzerland is a multilingual country located between Germany, France and Italy,
      which differ by dietary habits and related outcomes. We explored differences in
      food consumption as well as compliance to the Swiss food-based dietary guidelines
      (FBDG) across the German-, French-, and Italian-speaking regions. The 2014-2015
      nationwide cross-sectional survey was conducted among a stratified random sample
      of 2057 adults aged 18 to 75 years. Trained dietitians assessed food consumption
      via two non-consecutive 24-h dietary recalls using the international validated
      software GloboDiet(r). Recorded foods and beverages were classified into six
      groups and 31 subgroups relevant for assessing compliance to the FBDG (Swiss Food
      Pyramid). Usual daily intake distributions were modelled and weighted for
      sampling design, non-response, weekdays and season. Participation rate was 38%.
      Significant differences across regions were observed in 18 of 31 food subgroups
      (p <= 0.01). Weighted mean daily intakes in the German-, French- and Italian
      speaking regions were, respectively, 245 g, 155 g, 140 g for soft drinks, 273 g,
      214 g, 135 g for coffee, 127 g, 72 g, 109 g for milk, 32 g, 45 g, 43 g for red
      meat, 18 g, 29 g, 34 g for fish/seafood, 8.1 g, 6.4 g, 3.7 g for butter, and 206
      g, 214 g, 168 g for vegetables. The seven FBDGs were followed by <1% of the
      population. Four in 10 participants met >=3 FBDG. Eighteen percent of
      participants ate >=5 portions of fruit and vegetables a day, without regional
      differences. Food consumption substantially differed across the three linguistic
      regions of Switzerland. Adherence to FBDG was uniformly low. This highlights the
      potential influence of culture on diet. Nutritional education along with public
      health interventions are needed and may be most efficient if regionally targeted.

PMID- 29068400
TI  - Health in All Policies in South Australia-Did It Promote and Enact an Equity
      Perspective?
AB  - Mobilising cross-sectoral action is helpful in addressing the range of social
      determinants that contribute to health inequities. The South Australian Health in
      All Policies (SA HiAP) approach was implemented from 2007 to stimulate cross
      sector policy activity to address the social determinants of health to improve
      population wellbeing and reduce health inequities. This paper presents selected
      findings from a five year multi-methods research study of the SA HiAP approach
      and draws on data collected during interviews, observation, case studies, and
      document analysis. The analysis shows that SA HiAP had dual goals of facilitating
      joined-up government for co-benefits (process focus); and addressing social
      determinants of health and inequities through cross-sectoral policy activity
      (outcomes focus). Government agencies readily understood HiAP as providing tools
      for improving the process of intersectoral policy development, while the more
      distal outcome-focused intent of improving equity was not well understood and
      gained less traction. While some early rhetorical support existed for progressing
      an equity agenda through SA HiAP, subsequent economic pressures resulted in the
      government narrowing its priorities to economic goals. The paper concludes that
      SA HiAP's initial intentions to address equity were only partially enacted and
      little was done to reduce inequities. Emerging opportunities in SA, and
      internationally, including the UN Sustainable Development Goals, may revive
      interest in addressing equity.

PMID- 29068401
TI  - Determination of the Deacetylation Degree of Chitooligosaccharides.
AB  - The methods for determination of chitosan content recommended in the Chinese
      Pharmacopoeia and the European Pharmacopoeia are not applicable for evaluation of
      the extent of deacetylation (deacetylation degree, DD) in chitooligosaccharides
      (COS). This study explores two different methods for assessment of DD in COS
      having relatively high and low molecular weights: an acid-base titration with
      bromocresol green indicator and a first order derivative UV spectrophotometric
      method for assessment of DD in COS. The accuracy of both methods as a function of
      molecular weight was also investigated and compared to results obtained using 1H
      NMR spectroscopy. Our study demonstrates two simple, fast, widely adaptable,
      highly precise, accurate, and inexpensive methods for the effective determination
      of DD in COS, which have the potential for widespread commercial applications in
      developing country.

PMID- 29068403
TI  - A Robust Dynamic Heart-Rate Detection Algorithm Framework During Intense Physical
      Activities Using Photoplethysmographic Signals.
AB  - Dynamic accurate heart-rate (HR) estimation using a photoplethysmogram (PPG)
      during intense physical activities is always challenging due to corruption by
      motion artifacts (MAs). It is difficult to reconstruct a clean signal and extract
      HR from contaminated PPG. This paper proposes a robust HR-estimation algorithm
      framework that uses one-channel PPG and tri-axis acceleration data to reconstruct
      the PPG and calculate the HR based on features of the PPG and spectral analysis.
      Firstly, the signal is judged by the presence of MAs. Then, the spectral peaks
      corresponding to acceleration data are filtered from the periodogram of the PPG
      when MAs exist. Different signal-processing methods are applied based on the
      amount of remaining PPG spectral peaks. The main MA-removal algorithm (NFEEMD)
      includes the repeated single-notch filter and ensemble empirical mode
      decomposition. Finally, HR calibration is designed to ensure the accuracy of HR
      tracking. The NFEEMD algorithm was performed on the 23 datasets from the 2015
      IEEE Signal Processing Cup Database. The average estimation errors were 1.12 BPM
      (12 training datasets), 2.63 BPM (10 testing datasets) and 1.87 BPM (all 23
      datasets), respectively. The Pearson correlation was 0.992. The experiment
      results illustrate that the proposed algorithm is not only suitable for HR
      estimation during continuous activities, like slow running (13 training
      datasets), but also for intense physical activities with acceleration, like arm
      exercise (10 testing datasets).

PMID- 29068402
TI  - Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused
      with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy
      against PEDV.
AB  - Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative
      agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells
      and results in severe diarrhea and dehydration in neonatal suckling pigs with up
      to 100% mortality. The oral vaccine route is reported as a promising approach for
      inducing protective immunity against PEDV invasion. Furthermore, dendritic cells
      (DCs), professional antigen-presenting cells, link humoral and cellular immune
      responses for homeostasis of the intestinal immune environment. In this study, in
      order to explore an efficient oral vaccine against PEDV infection, a mucosal DC
      targeting oral vaccine was developed using Lactobacillus casei to deliver the DC
      targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE)
      antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin
      A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses
      via oral vaccination in vivo. Significant differences (p < 0.05) in the immune
      response levels were observed between probiotics expressing the COE-DCpep fusion
      protein and COE antigen alone, suggesting better immune efficiency of the
      probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE
      antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances
      vaccine antigen delivery efficiency, providing a useful strategy to induce
      efficient immune responses against PEDV infection.

PMID- 29068404
TI  - Effect of Dentin Wetness on the Bond Strength of Universal Adhesives.
AB  - The effects of dentin wetness on the bond strength and adhesive interface
      morphology of universal adhesives have been investigated using micro-tensile bond
      strength (MUTBS) testing and confocal laser scanning microscopy (CLSM). Seventy
      two human third molars were wet ground to expose flat dentin surfaces. They were
      divided into three groups according to the air-drying time of the dentin
      surfaces: 0 (without air drying), 5, and 10 s. The dentin surfaces were then
      treated with three universal adhesives: G-Premio Bond, Single Bond Universal, and
      All-Bond Universal in self-etch or etch-and-rinse mode. After composite build up,
      a MUTBS test was performed. One additional tooth was prepared for each group by
      staining the adhesives with 0.01 wt % of Rhodamine B fluorescent dye for CLSM
      analysis. The data were analyzed statistically using ANOVA and Tukey's post hoc
      tests (alpha = 0.05). Two-way ANOVA showed significant differences among the
      adhesive systems and dentin moisture conditions. An interaction effect was also
      observed (p < 0.05). One-way ANOVA showed that All-Bond Universal was the only
      material influenced by the wetness of the dentin surfaces. Wetness of the dentin
      surface is a factor influencing the micro-tensile bond strength of universal
      adhesives.

PMID- 29068405
TI  - Effect of Built-Up Edge Formation during Stable State of Wear in AISI 304
      Stainless Steel on Machining Performance and Surface Integrity of the Machined
      Part.
AB  - During machining of stainless steels at low cutting -speeds, workpiece material
      tends to adhere to the cutting tool at the tool-chip interface, forming built-up
      edge (BUE). BUE has a great importance in machining processes; it can
      significantly modify the phenomenon in the cutting zone, directly affecting the
      workpiece surface integrity, cutting tool forces, and chip formation. The
      American Iron and Steel Institute (AISI) 304 stainless steel has a high tendency
      to form an unstable BUE, leading to deterioration of the surface quality.
      Therefore, it is necessary to understand the nature of the surface integrity
      induced during machining operations. Although many reports have been published on
      the effect of tool wear during machining of AISI 304 stainless steel on surface
      integrity, studies on the influence of the BUE phenomenon in the stable state of
      wear have not been investigated so far. The main goal of the present work is to
      investigate the close link between the BUE formation, surface integrity and
      cutting forces in the stable sate of wear for uncoated cutting tool during the
      cutting tests of AISI 304 stainless steel. The cutting parameters were chosen to
      induce BUE formation during machining. X-ray diffraction (XRD) method was used
      for measuring superficial residual stresses of the machined surface through the
      stable state of wear in the cutting and feed directions. In addition, surface
      roughness of the machined surface was investigated using the Alicona microscope
      and Scanning Electron Microscopy (SEM) was used to reveal the surface distortions
      created during the cutting process, combined with chip undersurface analyses. The
      investigated BUE formation during the stable state of wear showed that the BUE
      can cause a significant improvement in the surface integrity and cutting forces.
      Moreover, it can be used to compensate for tool wear through changing the tool
      geometry, leading to the protection of the cutting tool from wear.

PMID- 29068398
TI  - Precision Nutrition and Omega-3 Polyunsaturated Fatty Acids: A Case for
      Personalized Supplementation Approaches for the Prevention and Management of
      Human Diseases.
AB  - BACKGROUND: Dietary essential omega-6 (n-6) and omega-3 (n-3) 18 carbon (18C-)
      polyunsaturated fatty acids (PUFA), linoleic acid (LA) and alpha-linolenic acid
      (ALA), can be converted (utilizing desaturase and elongase enzymes encoded by
      FADS and ELOVL genes) to biologically-active long chain (LC; >20)-PUFAs by
      numerous cells and tissues. These n-6 and n-3 LC-PUFAs and their metabolites (ex,
      eicosanoids and endocannabinoids) play critical signaling and structural roles in
      almost all physiologic and pathophysiologic processes. METHODS: This review
      summarizes: (1) the biosynthesis, metabolism and roles of LC-PUFAs; (2) the
      potential impact of rapidly altering the intake of dietary LA and ALA; (3) the
      genetics and evolution of LC-PUFA biosynthesis; (4) Gene-diet interactions that
      may lead to excess levels of n-6 LC-PUFAs and deficiencies of n-3 LC-PUFAs; and
      (5) opportunities for precision nutrition approaches to personalize n-3 LC-PUFA
      supplementation for individuals and populations. CONCLUSIONS: The rapid nature of
      transitions in 18C-PUFA exposure together with the genetic variation in the LC
      PUFA biosynthetic pathway found in different populations make mal-adaptations a
      likely outcome of our current nutritional environment. Understanding this genetic
      variation in the context of 18C-PUFA dietary exposure should enable the
      development of individualized n-3 LC-PUFA supplementation regimens to prevent and
      manage human disease.

PMID- 29068408
TI  - Recrystallization-Induced Surface Cracks of Carbon Ions Irradiated 6H-SiC after
      Annealing.
AB  - Single crystal 6H-SiC wafers with 4 degrees  off-axis [0001] orientation were
      irradiated with carbon ions and then annealed at 900  degrees C for different
      time periods. The microstructure and surface morphology of these samples were
      investigated by grazing incidence X-ray diffraction (GIXRD), scanning electron
      microscopy (SEM), and transmission electron microscopy (TEM). Ion irradiation
      induced SiC amorphization, but the surface was smooth and did not have special
      structures. During the annealing process, the amorphous SiC was recrystallized to
      form columnar crystals that had a large amount of twin structures. The longer the
      annealing time was, the greater the amount of recrystallized SiC would be. The
      recrystallization volume fraction was accorded with the law of the Johnson-Mehl
      Avrami equation. The surface morphology consisted of tiny pieces with an average
      width of approximately 30 nm in the annealed SiC. The volume shrinkage of
      irradiated SiC layer and the anisotropy of newly born crystals during annealing
      process produced internal stress and then induced not only a large number of
      dislocation walls in the non-irradiated layer but also the initiation and
      propagation of the cracks. The direction of dislocation walls was perpendicular
      to the growth direction of the columnar crystal. The longer the annealing time
      was, the larger the length and width of the formed crack would be. A quantitative
      model of the crack growth was provided to calculate the length and width of the
      cracks at a given annealing time.

PMID- 29068407
TI  - Prokaryotic Expression and Serodiagnostic Potential of Glyceraldehyde-3-Phosphate
      Dehydrogenase and Thioredoxin Peroxidase from Baylisascaris schroederi.
AB  - Baylisascaris schroederi, a roundworm parasite of giant pandas, badly affects the
      health of its hosts. Diagnosis of this disease currently depends mainly on
      sedimentation floatation and Polymerase Chain Reaction (PCR) methods to detect
      the eggs. However, neither of these methods is suitable for diagnosis of early
      stage panda baylisascariasis and no information on early diagnosis of this
      disease is available so far. Therefore, to develop an effective serologic
      diagnostic method, this study produced recombinant glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) and thioredoxin peroxidase (Tpx) proteins from B.
      schroederi using a prokaryotic expression system. We determined the immunological
      characteristics of these proteins and their location in the parasite. Indirect
      enzyme-linked immunosorbent assays (ELISAs) were established to detect B.
      schroederi infection in giant pandas based on GAPDH and Tpx respectively. The
      open reading frame of the GAPDH gene (1083 bp) encoded a 39 kDa protein, while
      the predicted molecular weight of Tpx (588 bp) was 21.6 kDa. Western-blotting
      analysis revealed that both recombinant proteins could be recognized with
      positive serum of pandas infected with B. schroederi. Immunohistochemical
      staining showed that the endogenous GAPDH of B. schroederi was widely distributed
      in the worm while Tpx was mainly localized in the muscle, eggs, gut wall, uterus
      wall and hypodermis. Serological tests showed that the GAPDH-based indirect ELISA
      had a sensitivity of 95.83% and specificity of 100%, while the test using Tpx as
      the antigen had sensitivity of 75% and specificity of 91.7%. Thus, B. schroederi
      Tpx is unsuitable as a diagnostic antigen for baylisascariasis, but B. schroederi
      GAPDH is a good candidate diagnostic antigen for B. schroederi in pandas.

PMID- 29068406
TI  - Studies on the Synthesis, Photophysical and Biological Evaluation of Some
      Unsymmetrical Meso-Tetrasubstituted Phenyl Porphyrins.
AB  - Abstract: We designed three unsymmetrical meso-tetrasubstituted phenyl porphyrins
      for further development as theranostic agents for cancer photodynamic therapy
      (PDT): 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3
      methoxyphenyl)porphyrin (P2.2), Zn(II)-5-(4-hydroxy-3-methoxyphenyl)-10,15,20
      tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Zn(II)2.2) and Cu(II)-5-(4-hydroxy-3
      methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin (Cu(II)2.2).
      The porphyrinic compounds were synthesized and their structures were confirmed by
      elemental analysis, FT-IR, UV-Vis, EPR and NMR. The compounds had a good
      solubility in polar/nonpolar media. P2.2 and, to a lesser extent, Zn(II)2.2 were
      fluorescent, albeit with low fluoresence quantum yields. P2.2 and Zn(II)2.2
      exhibited PDT-acceptable values of singlet oxygen generation. A "dark"
      cytotoxicity study was performed using cells that are relevant for the tumor
      niche (HT-29 colon carcinoma cells and L929 fibroblasts) and for blood
      (peripheral mononuclear cells). Cellular uptake of fluorescent compounds, cell
      viability/proliferation and death were evaluated. P2.2 was highlighted as a
      promising theranostic agent for PDT in solid tumors considering that P2.2
      generated PDT-acceptable singlet oxygen yields, accumulated into tumor cells and
      less in blood cells, exhibited good fluorescence within cells for imagistic
      detection, and had no significant cytotoxicity in vitro against tumor and normal
      cells. Complexing of P2.2 with Zn(II) or Cu(II) altered several of its PDT
      relevant properties. These are consistent arguments for further developing P2.2
      in animal models of solid tumors for in vivo PDT.

PMID- 29068409
TI  - Solvent and Copper Ion-Induced Synthesis of Pyridyl-Pyrazole-3-One Derivatives:
      Crystal Structure, Cytotoxicity.
AB  - Five novel compounds, methyl 5-(acetyloxy)-1-(6-bromo-2-pyridinyl)-1H-pyrazole-3
      carboxylate (1), methyl 1-(6-bromo-2-pyridinyl)-5-hydroxy-1H-pyrazole-3
      carboxylate (2), Trimethyl 1,1',1''-tris(6-bromo-2-pyridinyl)-5,5''-dihydroxy-5'
      oxo-1',5'-dihydro-1H,1''H-4,4': 4',4''-terpyrazole-3,3',3''-tricarboxylate (H2L1,
      3), [Cu2(L2)2].CH3OH (4), H2L2A.CH3CN (5) were synthesized. Compounds 1-5
      characterized by elemental analysis, IR, and X-ray single-crystal diffraction.
      And 1-3 were also characterized by 1H NMR, 13C NMR and ESI-MS. The H2L1, H2L2
      were formed by in-situ reaction. H2L2 and H2L2A are mesomer compounds which have
      two chiral carbons. The antitumor activity of compounds 1-5 against BEL-7404,
      HepG2, NCI-H460, T-24, A549 tumor cell lines were screened by methylthiazolyl
      tetrozolium (MTT) assay. The compounds 1, 2 showed weakly growth inhibition on
      the HepG2 cell lines. The HepG2 and A549 cell lines showed higher sensitivity to
      compound 4, while the IC50 values are 10.66, 28.09 MUM, respectively. It is worth
      noting that compounds 1-5 did not show cytotoxicity to human normal liver cell
      line HL-7702, suggesting its cytotoxic selectivity on these tumor cell lines.

PMID- 29068410
TI  - Can Inhibitors of Snake Venom Phospholipases A2 Lead to New Insights into Anti
      Inflammatory Therapy in Humans? A Theoretical Study.
AB  - Human phospholipase A2 (hPLA2) of the IIA group (HGIIA) catalyzes the hydrolysis
      of membrane phospholipids, producing arachidonic acid and originating potent
      inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a
      source of potential anti-inflammatory drugs, with different action mechanisms of
      known anti-inflammatory agents. For the study and development of new anti
      inflammatory drugs with this action mechanism, snake venom PLA2 (svPLA2) can be
      employed, since the svPLA2 has high similarity with the human PLA2 HGIIA. Despite
      the high similarity between these secretory PLA2s, it is still not clear if these
      toxins can really be employed as an experimental model to predict the
      interactions that occur with the human PLA2 HGIIA and its inhibitors. Thus, the
      present study aims to compare and evaluate, by means of theoretical calculations,
      docking and molecular dynamics simulations, as well as experimental studies, the
      interactions of human PLA2 HGIIA and two svPLA2s,Bothrops toxin II and Crotoxin B
      (BthTX-II and CB, respectively). Our theoretical findings corroborate
      experimental data and point out that the human PLA2 HGIIA and svPLA2 BthTX-II
      lead to similar interactions with the studied compounds. From our results, the
      svPLA2 BthTX-II can be used as an experimental model for the development of anti
      inflammatory drugs for therapy in humans.

PMID- 29068412
TI  - Influence of VO2 Nanoparticle Morphology on the Colorimetric Assay of H2O2 and
      Glucose.
AB  - Nanozyme-based colorimetric sensors have received considerable attention due to
      their unique properties. The size, shape, and surface chemistry of these
      nanozymes could dramatically influence their sensing behaviors. Herein, a
      comparative study of VO2 nanoparticles with different morphologies (nanofibers,
      nanosheets, and nanorods) was conducted and applied to the sensitive colorimetric
      detection of H2O2 and glucose. The peroxidase-like activities and mechanisms of
      VO2 nanoparticles were analyzed. Among the VO2 nanoparticles, VO2 nanofibers
      exhibited the best peroxidase-like activity. Finally, a comparative quantitative
      detections of H2O2 and glucose were done on fiber, sheet, and rod nanoparticles.
      Under the optimal reaction conditions, the lower limit of detection (LOD) of the
      VO2 nanofibers, nanosheets, and nanorods for H2O2 are found to be 0.018, 0.266,
      and 0.41 mM, respectively. The VO2 nanofibers, nanosheets, and nanorods show the
      linear response for H2O2 from 0.025-10, 0.488-62.5, and 0.488-15.625 mM,
      respectively. The lower limit of detection (LOD) of the VO2 nanofibers,
      nanosheets, and nanorods for glucose are found to be 0.009, 0.348, and 0.437 mM,
      respectively. The VO2 nanofibers, nanosheets, and nanorods show the linear
      response for glucose from 0.01-10, 0.625-15, and 0.625-10 mM, respectively. The
      proposed work will contribute to the nanozyme-based colorimetric assay.

PMID- 29068413
TI  - Phospholamban Is Downregulated by pVHL-Mediated Degradation through Oxidative
      Stress in Failing Heart.
AB  - The E3 ubiquitin ligase, von Hippel-Lindau (VHL), regulates protein expression by
      polyubiquitination. Although the protein VHL (pVHL) was reported to be involved
      in the heart function, the underlying mechanism is unclear. Here, we show that
      pVHL was upregulated in hearts from two types of genetically dilated
      cardiomyopathy (DCM) mice models. In comparison with the wild-type mouse, both
      DCM mice models showed a significant reduction in the expression of phospholamban
      (PLN), a potent inhibitor of sarco(endo)plasmic reticulum Ca2+-ATPase, and
      enhanced interaction between pVHL and PLN. To clarify whether pVHL is involved in
      PLN degradation in failing hearts, we used carbonylcyanide m
      chlorophenylhydrazone (CCCP), a mitochondrial membrane potential (MMP)-lowering
      reagent, to mimic the heart failure condition in PLN-expressing HEK293 cells and
      found that CCCP treatment resulted in PLN degradation and increased interaction
      between PLN and pVHL. However, these effects were reversed with the addition of N
      acetyl-l-cysteine. Furthermore, the co-transfection of VHL and PLN in HEK293
      cells decreased PLN expression under oxidative stress, whereas knockdown of VHL
      increased PLN expression both under normal and oxidative stress conditions.
      Together, we propose that oxidative stress upregulates pVHL expression to induce
      PLN degradation in failing hearts.

PMID- 29068411
TI  - Chemoenzymatic Preparation and Biophysical Properties of Sulfated Quercetin
      Metabolites.
AB  - Sulfated quercetin derivatives are important authentic standards for metabolic
      studies. Quercetin-3'-O-sulfate, quercetin-4'-O-sulfate, and quercetin-3-O
      sulfate as well as quercetin-di-O-sulfate mixture (quercetin-7,3'-di-O-sulfate,
      quercetin-7,4'-di-O-sulfate, and quercetin-3',4'-di-O-sulfate) were synthetized
      by arylsulfotransferase from Desulfitobacterium hafniense. Purified monosulfates
      and disulfates were fully characterized using MS and NMR and tested for their 1,1
      diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS+) and N,N-dimethyl-p-phenylenediamine (DMPD) radical
      scavenging, Folin-Ciocalteau reduction (FCR), ferric reducing antioxidant power
      (FRAP), and anti-lipoperoxidant activities in rat liver microsomes damaged by
      tert-butylhydroperoxide. Although, as expected, the sulfated metabolites were
      usually less active than quercetin, they remained still effective antiradical and
      reducing agents. Quercetin-3'-O-sulfate was more efficient than quercetin-4'-O
      sulfate in DPPH and FCR assays. In contrast, quercetin-4'-O-sulfate was the best
      ferric reductant and lipoperoxidation inhibitor. The capacity to scavenge ABTS+*
      and DMPD was comparable for all substances, except for disulfates, which were the
      most efficient. Quantum calculations and molecular dynamics simulations on
      membrane models supported rationalization of free radical scavenging and lipid
      peroxidation inhibition. These results clearly showed that individual metabolites
      of food bioactives can markedly differ in their biological activity. Therefore, a
      systematic and thorough investigation of all bioavailable metabolites with
      respect to native compounds is needed when evaluating food health benefits.

PMID- 29068414
TI  - iTRAQ-Based Identification of Proteins Related to Muscle Growth in the Pacific
      Abalone, Haliotis discus hannai.
AB  - The abalone Haliotis discus hannai is an important aquaculture species that is
      grown for human consumption. However, little is known of the genetic mechanisms
      governing muscle growth in this species, particularly with respect to proteomics.
      The isobaric tag for relative and absolute quantitation (iTRAQ) method allows for
      sensitive and accurate protein quantification. Our study was the first to use
      iTRAQ-based quantitative proteomics to investigate muscle growth regulation in H.
      discus hannai. Among the 1904 proteins identified from six samples, 125 proteins
      were differentially expressed in large specimens of H. discus hannai as compared
      to small specimens. In the large specimens, 47 proteins were upregulated and 78
      were downregulated. Many of the significant Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathways, including these differentially expressed proteins, were
      closely related to muscle growth, including apoptosis, thyroid hormone signaling,
      regulation of the actin cytoskeleton, and viral myocarditis (p < 0.05). Our
      quantitative real-time polymerase chain reaction (qRT-PCR) analyses suggested
      that the alterations in expression levels observed in the differentially
      expressed proteins were consistent with the alterations observed in the encoding
      mRNAs, indicating the repeatability of our proteomic approach. Our findings
      contribute to the knowledge of the molecular mechanisms of muscle growth in H.
      discus hannai.

PMID- 29068416
TI  - Effects of Hot-Hydrostatic Canned Extrusion on the Stock Utilization,
      Microstructure and Mechanical Properties of TiBw/TC4 Composites with Quasi
      Continuous Network.
AB  - In-situ TiB whisker-reinforced Ti-6Al-4V (TC4) titanium matrix composites
      (TiBw/TC4) with quasi-continuous networks were successfully fabricated by vacuum
      hot-pressing sintering. The effects of the hot-hydrostatic canned extrusion on
      stock utilization, microstructure and mechanical properties of the TiBw/TC4
      composites were investigated. It was satisfactory that the utilization of
      composites could be obviously improved by canned extrusion compared to that
      extruded without canned extrusion. The microstructure results showed that after
      canned extrusion the grain was refined and the TiB whiskers were distributed from
      a random array state to a state in which the whiskers were distributed along the
      extrusion direction. The properties testing results revealed that the tensile
      strength, the hardness and the ductility of the composites all significantly
      improved after extrusion due to the grain refinement and orientation of the TiB
      whisker caused by extrusion. Tensile fracture results showed that when the TiB
      whiskers were randomly distributed only part of them played a role in
      strengthening the matrix during the deformation process (as-sintered composites),
      while when the TiB whiskers were oriented all whiskers could strengthen the
      matrix during the tensile testing process (as-extruded composites).

PMID- 29068415
TI  - Association of Smoking with Metabolic Volatile Organic Compounds in Exhaled
      Breath.
AB  - Lung cancer (LC) screening will be more efficient if it is applied to a well
      defined high-risk population. Characteristics including metabolic byproducts may
      be taken into account to access LC risk more precisely. Breath examination
      provides a non-invasive method to monitor metabolic byproducts. However, the
      association between volatile organic compounds (VOCs) in exhaled breath and LC
      risk or LC risk factors is not studied. Exhaled breath samples from 122 healthy
      persons, who were given routine annual exam from December 2015 to December 2016,
      were analyzed using thermal desorption coupled with gas chromatography mass
      spectrometry (TD-GC-MS). Smoking characteristics, air quality, and other risk
      factors for lung cancer were collected. Univariate and multivariate analyses were
      used to evaluate the relationship between VOCs and LC risk factors. 7, 7, 11, and
      27 VOCs were correlated with smoking status, smoking intensity, years of smoking,
      and depth of inhalation, respectively. Exhaled VOCs are related to smoking and
      might have a potential to evaluate LC risk more precisely. Both an assessment of
      temporal stability and testing in a prospective study are needed to establish the
      performance of VOCs such as 2,5-dimethylfuranm and 4-methyloctane as lung cancer
      risk biomarkers.

PMID- 29068417
TI  - Surface Modification of Direct-Current and Radio-Frequency Oxygen Plasma
      Treatments Enhance Cell Biocompatibility.
AB  - The sand-blasting and acid etching (SLA) method can fabricate a rough topography
      for mechanical fixation and long-term stability of titanium implant, but can not
      achieve early bone healing. This study used two kinds of plasma treatments
      (Direct-Current and Radio-Frequency plasma) to modify the SLA-treated surface.
      The modification of plasma treatments creates respective power range and
      different content functional OH groups. The results show that the plasma
      treatments do not change the micron scale topography, and plasma-treated
      specimens presented super hydrophilicity. The X-ray photoelectron spectroscopy
      (XPS)-examined result showed that the functional OH content of the RF plasma
      treated group was higher than the control (SLA) and DC treatment groups. The
      biological responses (protein adsorption, cell attachment, cell proliferation,
      and differentiation) promoted after plasma treatments, and the cell responses,
      have correlated to the total content of amphoteric OH groups. The experimental
      results indicated that plasma treatments can create functional OH groups on SLA
      treated specimens, and the RF plasma-treated SLA implant thus has potential for
      achievement of bone healing in early stage of implantation.

PMID- 29068418
TI  - Sealing Ability of Alkaline Endodontic Cements versus Resin Cements.
AB  - Penetration of oral bacteria through root fillings leads to their long term
      failure. Dimensionally stable alkaline cements have been developed. A saliva
      challenge model was used to compare resistance to bacterial penetration of these
      alkaline cements to conventional root fillings that combine gutta percha (GP)
      with epoxy resin sealers. A sample of 140 human roots with single straight canals
      prepared to standard length and canal size were obturated with mineral trioxide
      aggregate (MTA) (Nex MTA or MTAmix), with an alkaline calcium hydroxide hard
      setting cement (Supercal), or with GP and a resin cement (either AH-Plus or
      Zirmix). Negative control roots were sealed with wax, while positive controls
      were left open. The test assemblies were gamma sterilised, then the coronal root
      face was exposed daily to fresh stimulated human saliva diluted in broth.
      Bacterial penetration was determined by assessing growth in sterile brain-heart
      infusion (BHI) medium in contact with the root apex. Using Kaplan-Meier survival
      analysis, in order of performance from highest to lowest: Negative control,
      Supercal, Nex MTA, Zirmix, MTAmix, GP + AH-Plus, and the positive control. In
      addition, statistically significant differences were noted between Supercal and
      AH-Plus, and between the two MTA cements. It can be concluded that alkaline
      cements, particularly Supercal, can show considerable resistance to bacterial
      penetration from constant saliva challenge, and provide superior sealing ability
      in comparison to resin cements. While this property is due mostly to dimensional
      stability, the release of hydroxide ions could be a contributing factor to
      impaired bacterial survival, and this aspect should be explored further.

PMID- 29068420
TI  - Assessment of SIP Buildings for Sustainable Development in Rural China Using AHP
      Grey Correlation Analysis.
AB  - Traditional rural residential construction has the problems of high energy
      consumption and severe pollution. In general, with sustainable development in the
      construction industry, rural residential construction should be aimed towards low
      energy consumption and low carbon emissions. To help achieve this objective, in
      this paper, we evaluated four different possible building structures using AHP
      Grey Correlation Analysis, which consists of the Analytic Hierarchy Process (AHP)
      and the Grey Correlation Analysis. The four structures included the traditional
      and currently widely used brick and concrete structure, as well as structure
      insulated panels (SIPs). Comparing the performances of economic benefit and
      carbon emission, the conclusion that SIPs have the best overall performance can
      be obtained, providing a reference to help builders choose the most appropriate
      building structure in rural China.

PMID- 29068419
TI  - FGF-2b and h-PL Transform Duct and Non-Endocrine Human Pancreatic Cells into
      Endocrine Insulin Secreting Cells by Modulating Differentiating Genes.
AB  - Background: Diabetes mellitus (DM) is a multifactorial disease orphan of a cure.
      Regenerative medicine has been proposed as novel strategy for DM therapy. Human
      fibroblast growth factor (FGF)-2b controls beta-cell clusters via autocrine
      action, and human placental lactogen (hPL)-A increases functional beta-cells. We
      hypothesized whether FGF-2b/hPL-A treatment induces beta-cell differentiation
      from ductal/non-endocrine precursor(s) by modulating specific genes expression.
      Methods: Human pancreatic ductal-cells (PANC-1) and non-endocrine pancreatic
      cells were treated with FGF-2b plus hPL-A at 500 ng/mL. Cytofluorimetry and
      Immunofluorescence have been performed to detect expression of endocrine, ductal
      and acinar markers. Bromodeoxyuridine incorporation and annexin-V quantified
      cells proliferation and apoptosis. Insulin secretion was assessed by RIA kit, and
      electron microscopy analyzed islet-like clusters. Results: Increase in PANC-1
      duct cells de-differentiation into islet-like aggregates was observed after FGF
      2b/hPL-A treatment showing ultrastructure typical of islets-aggregates. These
      clusters, after stimulation with FGF-2b/hPL-A, had significant (p < 0.05)
      increase in insulin, C-peptide, pancreatic and duodenal homeobox 1 (PDX-1),
      Nkx2.2, Nkx6.1, somatostatin, glucagon, and glucose transporter 2 (Glut-2),
      compared with control cells. Markers of PANC-1 (Cytokeratin-19, MUC-1, CA19-9)
      were decreased (p < 0.05). These aggregates after treatment with FGF-2b/hPL-A
      significantly reduced levels of apoptosis. Conclusions: FGF-2b and hPL-A are
      promising candidates for regenerative therapy in DM by inducing de
      differentiation of stem cells modulating pivotal endocrine genes.

PMID- 29068421
TI  - New Pyrazole-Hydrazone Derivatives: X-ray Analysis, Molecular Structure
      Investigation via Density Functional Theory (DFT) and Their High In-Situ
      Catecholase Activity.
AB  - The development of low-cost catalytic systems that mimic the activity of
      tyrosinase enzymes (Catechol oxidase) is of great promise for future biochemistry
      technologic demands. Herein, we report the synthesis of new biomolecules systems
      based on hydrazone derivatives containing a pyrazole moiety (L1-L6) with superior
      catecholase activity. Crystal structures of L1 and L2 biomolecules were
      determined by X-ray single crystal diffraction (XRD). Optimized geometrical
      parameters were calculated by density functional theory (DFT) at B3LYP/6-31G (d,
      p) level and were found to be in good agreement with single crystal XRD data.
      Copper (II) complexes of the compounds (L1-L6), generated in-situ, were
      investigated for their catalytic activities towards the oxidation reaction of
      catechol to ortho-quinone with the atmospheric dioxygen, in an attempt to model
      the activity of the copper containing enzyme tyrosinase. The studies showed that
      the activities depend on four parameters: the nature of the ligand, the nature of
      counter anion, the nature of solvent and the concentration of ligand. The Cu(II)
      ligands, given here, present the highest catalytic activity (72.920 MUmol.L-1.min
      1) among the catalysts recently reported in the existing literature.

PMID- 29068422
TI  - Anticancer Effects of Resveratrol-Loaded Solid Lipid Nanoparticles on Human
      Breast Cancer Cells.
AB  - In this study, resveratrol-loaded solid lipid nanoparticles (Res-SLNs) were
      successfully designed to treat MDA-MB-231 cells. The Res-SLNs were prepared using
      emulsification and low-temperature solidification method. The Res-SLNs were
      spherical, with small size, negative charge, and narrow size distribution.
      Compared with free resveratrol, the Res-SLNs displayed a superior ability in
      inhibiting the proliferation of MDA-MB-231 cells. In addition, Res-SLNs exhibited
      much stronger inhibitory effects on the invasion and migration of MDA-MB-231
      cells. Western blot analysis revealed that Res-SLNs could promote the ratio of
      Bax/Bcl-2 but decreased the expression of cyclinD1 and c-Myc. These results
      indicate that the Res-SLN may have great potential for breast cancer treatment.

PMID- 29068424
TI  - High Thermal Conductivity of Copper Matrix Composite Coatings with Highly-Aligned
      Graphite Nanoplatelets.
AB  - Nanocomposite coatings with highly-aligned graphite nanoplatelets in a copper
      matrix were successfully fabricated by electrodeposition. For the first time, the
      disposition and thermal conductivity of the nanofiller has been evaluated. The
      degree of alignment and inclination of the filling materials has been
      quantitatively evaluated by polarized micro-Raman spectroscopy. The room
      temperature values of the thermal conductivity were extracted for the graphite
      nanoplatelets by the dependence of the Raman G-peak frequency on the laser power
      excitation. Temperature dependency of the G-peak shift has been also measured.
      Most remarkable is the global thermal conductivity of 640 +/- 20 W.m-1.K-1 (+57%
      of copper) obtained for the composite coating by the flash method. Our
      experimental results are accounted for by an effective medium approximation (EMA)
      model that considers the influence of filler geometry, orientation, and thermal
      conductivity inside a copper matrix.

PMID- 29068423
TI  - Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the
      Early Diagnosis and Prognosis of Cancer.
AB  - During the past century, our understanding of cancer diagnosis and treatment has
      been based on a monogenic approach, and as a consequence our knowledge of the
      clinical genetic underpinnings of cancer is incomplete. Since the completion of
      the human genome in 2003, it has steered us into therapeutic target discovery,
      enabling us to mine the genome using cutting edge proteogenomics tools. A number
      of novel and promising cancer targets have emerged from the genome project for
      diagnostics, therapeutics, and prognostic markers, which are being used to
      monitor response to cancer treatment. The heterogeneous nature of cancer has
      hindered progress in understanding the underlying mechanisms that lead to
      abnormal cellular growth. Since, the start of The Cancer Genome Atlas (TCGA), and
      the International Genome consortium projects, there has been tremendous progress
      in genome sequencing and immense numbers of cancer genomes have been completed,
      and this approach has transformed our understanding of the diagnosis and
      treatment of different types of cancers. By employing Genomics and proteomics
      technologies, an immense amount of genomic data is being generated on clinical
      tumors, which has transformed the cancer landscape and has the potential to
      transform cancer diagnosis and prognosis. A complete molecular view of the cancer
      landscape is necessary for understanding the underlying mechanisms of cancer
      initiation to improve diagnosis and prognosis, which ultimately will lead to
      personalized treatment. Interestingly, cancer proteome analysis has also allowed
      us to identify biomarkers to monitor drug and radiation resistance in patients
      undergoing cancer treatment. Further, TCGA-funded studies have allowed for the
      genomic and transcriptomic characterization of targeted cancers, this analysis
      aiding the development of targeted therapies for highly lethal malignancy. High
      throughput technologies, such as complete proteome, epigenome, protein-protein
      interaction, and pharmacogenomics data, are indispensable to glean into the
      cancer genome and proteome and these approaches have generated multidimensional
      universal studies of genes and proteins (OMICS) data which has the potential to
      facilitate precision medicine. However, due to slow progress in computational
      technologies, the translation of big omics data into their clinical aspects have
      been slow. In this review, attempts have been made to describe the role of high
      throughput genomic and proteomic technologies in identifying a panel of
      biomarkers which could be used for the early diagnosis and prognosis of cancer.

PMID- 29068425
TI  - Exceptional Chromosomal Evolution and Cryptic Speciation of Blind Mole Rats
      Nannospalax leucodon (Spalacinae, Rodentia) from South-Eastern Europe.
AB  - Mole rats are exclusively subterranean and highly specialized rodents. Their long
      lifespans, remarkable anti-cancer mechanisms, and various distinctive adaptive
      features make them a useful research model. Moreover, opposing convergence of
      morphological traits, they have developed extremely high karyotype variability.
      Thus, 74 chromosomal forms have been described so far and new ones are being
      revealed continuously. These evolved during the process of rapid radiation and
      occur in different biogeographical regions. During research into their
      reproductive biology we have already provided substantial evidence for species
      level separation of these taxa. Here, we review diverse chromosomal forms of the
      lesser blind mole rat, Mediterranean Nannospalax leucodon, distributed in South
      eastern Europe, their karyotype records, biogeography, origin, and phylogeny from
      our extensive research. In the light of new data from molecular genetic studies,
      we question some former valuations and propose a cryptospecies rank for seven
      reproductively isolated chromosomal forms with sympatric and parapatric
      distribution and clear ecogeographical discrepances in their habitats, as well as
      new experimental and theoretical methods for understanding the courses of
      speciation of these unique fossorial mammals.

PMID- 29068427
TI  - A Rapid One-Step Process for Fabrication of Biomimetic Superhydrophobic Surfaces
      by Pulse Electrodeposition.
AB  - Inspired by some typical plants such as lotus leaves, superhydrophobic surfaces
      are commonly prepared by a combination of low surface energy materials and
      hierarchical micro/nano structures. In this work, superhydrophobic surfaces on
      copper substrates were prepared by a rapid, facile one-step pulse
      electrodepositing process, with different duty ratios in an electrolyte
      containing lanthanum chloride (LaCl3.6H2O), myristic acid (CH3(CH2)12COOH), and
      ethanol. The equivalent electrolytic time was only 10 min. The surface
      morphology, chemical composition and superhydrophobic property of the pulse
      electrodeposited surfaces were fully investigated with SEM, EDX, XRD, contact
      angle meter and time-lapse photographs of water droplets bouncing method. The
      results show that the as-prepared surfaces have micro/nano dual scale structures
      mainly consisting of La[CH3(CH2)12COO]3 crystals. The maximum water contact angle
      (WCA) is about 160.9 degrees , and the corresponding sliding angle is about 5
      degrees . This method is time-saving and can be easily extended to other
      conductive materials, having a great potential for future applications.

PMID- 29068426
TI  - Preparation and Characterization of Resorbable Bacterial Cellulose Membranes
      Treated by Electron Beam Irradiation for Guided Bone Regeneration.
AB  - Bacterial cellulose (BC) is an excellent biomaterial with many medical
      applications. In this study, resorbable BC membranes were prepared for guided
      bone regeneration (GBR) using an irradiation technique for applications in the
      dental field. Electron beam irradiation (EI) increases biodegradation by severing
      the glucose bonds of BC. BC membranes irradiated at 100 kGy or 300 kGy were used
      to determine optimal electron beam doses. Electron beam irradiated BC membranes
      (EI-BCMs) were evaluated by scanning electron microscopy (SEM), attenuated total
      reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, thermal
      gravimetric analysis (TGA), and using wet tensile strength measurements. In
      addition, in vitro cell studies were conducted in order to confirm the
      cytocompatibility of EI-BCMs. Cell viabilities of NIH3T3 cells on 100k and 300k
      EI-BCMs (100 kGy and 300 kGy irradiated BC membranes) were significantly greater
      than on NI-BCMs after 3 and 7 days (p < 0.05). Bone regeneration by EI-BCMs and
      their biodegradabilities were also evaluated using in vivo rat calvarial defect
      models for 4 and 8 weeks. Histometric results showed 100k EI-BCMs exhibited
      significantly larger new bone area (NBA; %) than 300k EI-BCMs at 8 weeks after
      implantation (p < 0.05). Mechanical, chemical, and biological analyses showed EI
      BCMs effectively interacted with cells and promoted bone regeneration.

PMID- 29068428
TI  - Magnetoelectric Transverse Gradient Sensor with High Detection Sensitivity and
      Low Gradient Noise.
AB  - We report, theoretically and experimentally, the realization of a high detection
      performance in a novel magnetoelectric (ME) transverse gradient sensor based on
      the large ME effect and the magnetic field gradient (MFG) technique in a pair of
      magnetically-biased, electrically-shielded, and mechanically-enclosed ME
      composites having a transverse orientation and an axial separation. The output
      voltage of the gradient sensor is directly obtained from the transverse MFG
      induced difference in ME voltage between the two ME composites and is calibrated
      against transverse MFGs to give a high detection sensitivity of 0.4-30.6 V/(T/m),
      a strong common-mode magnetic field noise rejection rate of <-14.5 dB, a small
      input-output nonlinearity of <10 ppm, and a low gradient noise of 0.16-620 nT/m/
      Hz in a broad frequency range of 1 Hz-170 kHz under a small baseline of 35 mm. An
      analysis of experimental gradient noise spectra obtained in a magnetically
      unshielded laboratory environment reveals the domination of the pink (1/f) noise,
      dielectric loss noise, and power-frequency noise below 3 kHz, in addition to the
      circuit noise above 3 kHz, in the gradient sensor. The high detection
      performance, together with the added merit of passive and direct ME conversion by
      the large ME effect in the ME composites, makes the gradient sensor suitable for
      the passive, direct, and broadband detection of transverse MFGs.

PMID- 29068429
TI  - 3-Axis Fully-Integrated Capacitive Tactile Sensor with Flip-Bonded CMOS on LTCC
      Interposer.
AB  - This paper reports a 3-axis fully integrated differential capacitive tactile
      sensor surface-mountable on a bus line. The sensor integrates a flip-bonded
      complementary metal-oxide semiconductor (CMOS) with capacitive sensing circuits
      on a low temperature cofired ceramic (LTCC) interposer with Au through vias by Au
      Au thermo-compression bonding. The CMOS circuit and bonding pads on the sensor
      backside were electrically connected through Au bumps and the LTCC interposer,
      and the differential capacitive gap was formed by an Au sealing frame. A
      diaphragm for sensing 3-axis force was formed in the CMOS substrate. The
      dimensions of the completed sensor are 2.5 mm in width, 2.5 mm in length, and
      0.66 mm in thickness. The fabricated sensor output coded 3-axis capacitive
      sensing data according to applied 3-axis force by three-dimensional (3D)-printed
      pins. The measured sensitivity was as high as over 34 Count/mN for normal force
      and 14 to 15 Count/mN for shear force with small noise, which corresponds to less
      than 1 mN. The hysteresis and the average cross-sensitivity were also found to be
      less than 2% full scale and 11%, respectively.

PMID- 29068431
TI  - Towards Intelligent Interpretation of Low Strain Pile Integrity Testing Results
      Using Machine Learning Techniques.
AB  - Low strain pile integrity testing (LSPIT), due to its simplicity and low cost, is
      one of the most popular NDE methods used in pile foundation construction. While
      performing LSPIT in the field is generally quite simple and quick, determining
      the integrity of the test piles by analyzing and interpreting the test signals
      (reflectograms) is still a manual process performed by experienced experts only.
      For foundation construction sites where the number of piles to be tested is
      large, it may take days before the expert can complete interpreting all of the
      piles and delivering the integrity assessment report. Techniques that can
      automate test signal interpretation, thus shortening the LSPIT's turnaround time,
      are of great business value and are in great need. Motivated by this need, in
      this paper, we develop a computer-aided reflectogram interpretation (CARI)
      methodology that can interpret a large number of LSPIT signals quickly and
      consistently. The methodology, built on advanced signal processing and machine
      learning technologies, can be used to assist the experts in performing both
      qualitative and quantitative interpretation of LSPIT signals. Specifically, the
      methodology can ease experts' interpretation burden by screening all test piles
      quickly and identifying a small number of suspected piles for experts to perform
      manual, in-depth interpretation. We demonstrate the methodology's effectiveness
      using the LSPIT signals collected from a number of real-world pile construction
      sites. The proposed methodology can potentially enhance LSPIT and make it even
      more efficient and effective in quality control of deep foundation construction.

PMID- 29068430
TI  - Systemic Inflammation, Oxidative Damage to Nucleic Acids, and Metabolic Syndrome
      in the Pathogenesis of Psoriasis.
AB  - In the pathogenesis of psoriasis, systemic inflammation and oxidative stress play
      mutual roles interrelated with metabolic syndrome (MetS). This study aims to map
      the selected markers of inflammation (C-reactive protein (CRP)), oxidative damage
      to nucleic acids (DNA/RNA damage; 8-hydroxy-2'-deoxyguanosine, 8
      hydroxyguanosine, and 8-hydroxyguanine), and the parameters of MetS (waist
      circumference, fasting glucose, triglycerides, high-density lipoprotein (HDL)
      cholesterol, diastolic and systolic blood pressure) in a group of 37 patients
      with psoriasis (62% of MetS) and in 43 healthy controls (42% of MetS). Levels of
      CRP, DNA/RNA damage, fasting glucose, and triglycerides were significantly
      elevated in patients. MetS in conjunction with psoriasis was associated with high
      levels of CRP, significantly higher than in control subjects without MetS.
      Patients with MetS exhibited further DNA/RNA damage, which was significantly
      higher in comparison with the control group. Our study supports the independent
      role of psoriasis and MetS in the increase of CRP and DNA/RNA damage. The
      psoriasis contributes to an increase in the levels of both effects more
      significantly than MetS. The psoriasis also diminished the relationship between
      CRP and oxidative damage to nucleic acids existent in controls.

PMID- 29068432
TI  - Early career investigator highlight-December.

PMID- 29068434
TI  - Prothrombotic state in young females with severe early-onset obesity.

PMID- 29068433
TI  - Diet and exercise interventions for pediatric cancer patients during therapy:
      tipping the scales for better outcomes.
AB  - Obesity at diagnosis is a negative prognostic indicator for several pediatric
      cancers including acute leukemia and bone tumors. Incidence of obesity in
      children has increased three-fold over the past 2 decades, and causes for this
      include poor diet, excessive caloric intake, and lack of physical activity, which
      are collectively referred to as energy balance-related behaviors. Few energy
      balance interventions have been implemented in pediatric cancer patients during
      treatment, and here we will probe the rationale for pursuing such studies. The
      need to modify composition of calories consumed and to identify specific
      beneficial exercise regimens will be discussed, relative to weight reduction or
      management.

PMID- 29068437
TI  - Paediatrics: Integrating genomics to dig deeper into Wilms tumour biology.

PMID- 29068435
TI  - Dimethyloxalylglycine preserves the intestinal microvasculature and protects
      against intestinal injury in a neonatal mouse NEC model: role of VEGF signaling.
AB  - BackgroundNecrotizing enterocolitis (NEC) is a devastating neonatal disease
      characterized by intestinal necrosis. Hypoxia-inducible factor-1alpha (HIF
      1alpha) has a critical role in cellular oxygen homeostasis. Here, we hypothesized
      that prolyl hydroxylase (PHD) inhibition, which stabilizes HIF-1alpha, protects
      against NEC by promoting intestinal endothelial cell proliferation and improving
      intestinal microvascular integrity via vascular endothelial growth factor (VEGF)
      signaling.MethodsTo assess the role of PHD inhibition in a neonatal mouse NEC
      model, we administered dimethyloxalylglycine (DMOG) or vehicle to pups before or
      during the NEC protocol, and determined mortality and incidence of severe
      intestinal injury. We assessed intestinal VEGF by western blot analysis and
      quantified endothelial cell and epithelial cell proliferation following
      immunofluorescence.ResultsDMOG decreased mortality and incidence of severe NEC,
      increased intestinal VEGF expression, and increased intestinal villus endothelial
      and epithelial cell proliferation in experimental NEC. Inhibiting VEGFR2
      signaling eliminated DMOG's protective effect on intestinal injury severity,
      survival, and endothelial cell proliferation while sparing DMOG's protective
      effect on intestinal epithelial cell proliferation.ConclusionDMOG upregulates
      intestinal VEGF, promotes endothelial cell proliferation, and protects against
      intestinal injury and mortality in experimental NEC in a VEGFR2 dependent manner.
      DMOG's protective effect on the neonatal intestinal mucosa may be mediated via
      VEGFR2 dependent improvement of the intestinal microvasculature.

PMID- 29068438
TI  - Clinical Decision-Making: Observing the Smartphone User An Observational Study in
      Predicting Acute Surgical Patients' Suitability for Discharge.
AB  - INTRODUCTION: An accurate and rapid assessment of an acutely unwell patient's
      clinical status is paramount for the physician. There is an increasing trend to
      rely on investigations and results to inform a clinician of a patient's clinical
      status, with the subtleties of clinical observation often ignored. The aim of
      this study was to determine if a patient's use of a smartphone during the initial
      clinical assessment by a surgical consultant could be used as a surrogate marker
      for patient well-being, represented as their suitability for sameday discharge.
      METHODS: This was a prospective observational study performed over 2 periods at a
      tertiary hospital in South Australia. All patients admitted by junior surgical
      doctors from the emergency department to the acute surgical unit were eligible
      for inclusion. Upon consultant review, their status as a smartphone user was
      recorded in addition to their duration of hospital stay and basic demographic
      data. All patients and all but 1 of the consultants were blinded to the trial.
      RESULTS: Two hundred and twenty-one patients were eligible for inclusion. Of
      these patients, 11.3% were observed to be using a smartphone and 23.5% of
      patients were discharged home on day 1. Those who were observed to be using a
      smartphone were 5.29 times more likely to be discharged home on day 1 and were
      less likely to be subsequently readmitted. CONCLUSIONS: The addition of the
      smartphone sign to a surgeon's clinical acumen can provide yet another tool in
      aiding the decision for suitability for discharge.

PMID- 29068439
TI  - Perception of Resources Spent on Defensive Medicine and History of Being Sued
      Among Hospitalists: Results from a National Survey.
AB  - The United States spends substantially more per capita for healthcare than any
      other nation. Defensive medicine is 1 source of such spending, but its extent is
      unclear. Using a national survey of approximately 1500 US hospitalists, we report
      the estimates the US hospitalists provided of the percent of resources spent on
      defensive medicine and correlates of their estimates. We also ascertained how
      many reported being sued. Sixty-eight percent of eligible recipients responded.
      Overall, respondents estimated that 37.5% of healthcare costs are due to
      defensive medicine. Just over 25% of our respondents, including 55% of those in
      practice for 20 years or more, reported being sued for medical malpractice.
      Veterans Affairs (VA) hospital affiliation, more years practicing as a physician,
      being male, and being a non-Hispanic white individual were all independently
      associated with decreased estimates of resources spent for defensive medicine.

PMID- 29068440
TI  - The TEND (Tomorrow's Expected Number of Discharges) Model Accurately Predicted
      the Number of Patients Who Were Discharged from the Hospital the Next Day.
AB  - BACKGROUND: Knowing the number of discharges that will occur is important for
      administrators when hospital occupancy is close to or exceeds 100%. This
      information will facilitate decision making such as whether to bring in extra
      staff, cancel planned surgery, or implement measures to increase the number of
      discharges. We derived and internally validated the TEND (Tomorrow's Expected
      Number of Discharges) model to predict the number of discharges from hospital in
      the next day. METHODS: We identified all patients greater than 1 year of age
      admitted to a multisite academic hospital between 2013 and 2015. In derivation
      patients we applied survival-tree methods to patient-day covariates (patient age,
      sex, comorbidities, location, admission urgency, service, campus, and weekday)
      and identified risk strata having unique discharge patterns. Discharge
      probability in each risk strata for the previous 6 months was summed to calculate
      each day's expected number of discharges. RESULTS: Our study included 192,859
      admissions. The daily number of discharges varied extensively (median 139;
      interquartile range [IQR] 95-160; range 39-214). We identified 142 discharge risk
      strata. In the validation patients, the expected number of daily discharges
      strongly predicted the observed number of discharges (adjusted R2 = 89.2%; P <
      0.0001). The relative difference between observed and expected number of
      discharges was small (median 1.4%; IQR -5.5% to 7.1%). CONCLUSION: The TEND model
      accurately predicted the daily number of discharges using information typically
      available within hospital data warehouses. Further study is necessary to
      determine if this information improves hospital bed management.

PMID- 29068436
TI  - GWAS meta-analysis reveals novel loci and genetic correlates for general
      cognitive function: a report from the COGENT consortium.
AB  - This corrects the article DOI: 10.1038/mp.2016.244.

PMID- 29068441
TI  - Plasmonic nanocone arrays for rapid and detailed cell lysate surface enhanced
      Raman spectroscopy analysis.
AB  - In this work, we develop, fabricate, and characterize a plasmonic nanocone array
      surface enhanced Raman spectroscopy (SERS) substrate with a uniform enhancement
      factor on the micron scale for qualitative and quantiative cell and cell lysate
      analysis. This work demonstrates how SERS substrates can be used as cell-based
      biosensors given that the enhancement factor of the substrate is sufficient for
      Raman detection and that the uniformity is high over the applicable surface area.
      These requirements allow accurate and quantitative comparisons between nonuniform
      samples under varying biochemical conditions. We apply the developed SERS
      substrate for Raman measurements and mapping of HeLa cells and cell lysate. This
      method is used for identification of UV-induced damage and detection of nanomolar
      concentrations of methylated guanine spiked in cell lysate samples.

PMID- 29068442
TI  - Two ruthenium complexes capable of storing multiple electrons on a single ligand 
      photophysical, photochemical and electrochemical properties of
      [Ru(phen)2(TAPHAT)]2+ and [Ru(phen)2(TAPHAT)Ru(phen)2]4.
AB  - The photophysical, photochemical and electrochemical properties of two newly
      synthesized ruthenium complexes, [Ru(phen)2(TAPHAT)]2+ and
      [Ru(phen)2(TAPHAT)Ru(phen)2]4+, are reported. We have developed a novel synthetic
      methodology that involves the metal-free oxidative coupling of diamino compounds
      to form a desired "pyrazine-type" core. This methodology is employed both on the
      free diamino ligand as well as on the different ruthenium complexes, therefore
      illustrating the applicability of this reaction. The TAPHAT ligand, which
      possesses 7 aromatic rings and 10 nitrogen atoms for 20 carbon atoms, gives rise
      to ruthenium complexes that can undergo up to three consecutive reductions
      centered on said ligand, a critical parameter for electron storage applications.
      A temperature-dependent study has confirmed the presence of a 4th MLCT state.
      Excited-state quenching in the presence of guanine or hydroquinone allows to
      foresee biomedical applications.

PMID- 29068443
TI  - A study of the Group 1 metal tetra-aza macrocyclic complexes [M(Me4cyclen)(L)]+
      using electronic structure calculations.
AB  - Metal-cyclen complexes have a number of important applications. However, the
      coordination chemistry between metal ions and cyclen-based macrocycles is much
      less well studied compared to their metal ion-crown ether analogues. This work,
      which makes a contribution to address this imbalance by studying complex ions of
      the type [M(Me4cyclen)(L)]+, was initiated by results of an experimental study
      which prepared some Group 1 metal cyclen complexes, namely
      [Li(Me4cyclen)(H2O)][BArF] and [Na(Me4cyclen)(THF)][BArF] and obtained their X
      ray crystal structures [J. M. Dyke, W. Levason, M. E. Light, D. Pugh, G. Reid, H.
      Bhakhoa, P. Ramasami, and L. Rhyman, Dalton Trans., 2015, 44, 13853]. The lowest
      [M(Me4cyclen)(L)]+ minimum energy structures (M = Li, Na, K, and L = H2O, THF,
      DEE, MeOH, DCM) are studied using density functional theory (DFT) calculations.
      The geometry of each [M(Me4cyclen)(L)]+ structure and, in particular, the
      conformation of L are found to be mainly governed by steric hindrance which
      decreases as the size of the ionic radius increases from Li+ -> Na+ -> K+. Good
      agreement of computed geometrical parameters of [Li(Me4cyclen)(H2O)]+ and
      [Na(Me4cyclen)(THF)]+ with the corresponding geometrical parameters derived from
      the crystal structures [Li(Me4cyclen)(H2O)]+[BArF]- and
      [Na(Me4cyclen)(THF)]+[BArF]- is obtained. Bonding analysis indicates that the
      stability of the [M(Me4cyclen)(L)]+ structures originates mainly from ionic
      interaction between the Me4cyclen/L ligands and the M+ centres. The experimental
      observation that [M(Me4cyclen)(L)]+[BArF]- complexes could be prepared in
      crystalline form for M+ = Li+ and Na+, but that experiments aimed at synthesising
      the corresponding K+, Rb+, and Cs+ complexes failed resulting in formation of
      [Me4cyclenH][BArF] is investigated using DFT and explicitly correlated
      calculations, and explained by considering production of [Me4cyclenH]+ by a
      hydrolysis reaction, involving traces of water, which competes with
      [M(Me4cyclen)(L)]+ formation. [Me4cyclenH]+ formation dominates for M+ = K+, Rb+,
      and Cs+ whereas formation of [M(Me4cyclen)(L)]+ is energetically favoured for M+
      = Li+ and Na+. The results indicate that the number and type of ligands, play a
      key role in stabilising the [M(Me4cyclen)]+ complexes and it is hoped that this
      work will encourage experimentalists to prepare and characterise other
      [M(Me4cyclen)(L)]+ complexes.

PMID- 29068444
TI  - Structural convergence properties of amorphous InGaZnO4 from simulated liquid
      quench methods.
AB  - The study of structural properties of amorphous structures is complicated by the
      lack of long-range order and necessitates the use of both cutting-edge computer
      modeling and experimental techniques. With regards to the computer modeling, many
      questions on convergence arise when trying to assess the accuracy of a simulated
      system. What cell size maximizes the accuracy while remaining computationally
      efficient? More importantly, does averaging multiple smaller cells adequately
      describe features found in bulk amorphous materials? How small is too small? The
      aims of this work are: (1) to report a newly developed set of pair potentials for
      InGaZnO4 and (2) to explore the effects of structural parameters such as
      simulation cell size and numbers on the structural convergence of amorphous
      InGaZnO4. The total number of formula units considered over all runs is found to
      be the critical factor in convergence as long as the cell considered contains a
      minimum of circa fifteen formula units. There is qualitative agreement between
      these simulations and X-ray total scattering data - peak trends and locations are
      consistently reproduced while intensities are weaker. These new IGZO pair
      potentials are a valuable starting point for future structural refinement
      efforts.

PMID- 29068445
TI  - MoS2/Pt nanocomposite-functionalized microneedle for real-time monitoring of
      hydrogen peroxide release from living cells.
AB  - This work describes the adaptive use of a conventional stainless steel
      acupuncture needle as the electrode substrate for construction of a molybdenum
      disulfide (MoS2) and platinum nanoparticles (PtNPs) layer-modified microneedle
      sensor for real-time monitoring of hydrogen peroxide (H2O2) release from living
      cells. To construct the nanocomposite-functionalized microneedle, the needle
      surface was first coated with a gold film by ion sputtering to enhance the
      conductivity. Subsequently, an electrochemical deposition method was successfully
      employed to deposit MoS2 nanosheet and Pt nanoparticles on the needle tip as the
      sensing interface. Electrochemical study demonstrated that the MoS2/PtNPs
      nanocomposite-modified needle exhibited excellent catalytic performance and low
      over-potential toward the reduction of H2O2. Not only did the microneedle achieve
      a wide linear range from 1 to 100 MUmol L-1 with a limit of detection down to
      0.686 MUmol L-1, but it also realized the highly specific detection of H2O2.
      Owing to these remarkable analytical advantages, the prepared microneedle was
      applied to determine H2O2 release from living cells with satisfactory results.
      The MoS2/PtNPs nanocomposite-functionalized microneedle sensor is simple and
      affordable, and can serve as a promising electrochemical nonenzymatic sensing
      platform. Moreover, this superfine needle sensor shows great potential for real
      time monitoring of reactive oxygen species in vivo with minimal damage.

PMID- 29068448
TI  - Color manipulation through microchip tinting for colorimetric detection using hue
      image analysis.
AB  - Colorimetry with microfluidic devices has been proven to be an advantageous
      method for in situ analyses where limited resources and rapid response for
      untrained users are desired. Image analysis using a small camera or cell phone
      can be easily incorporated for an objective readout, eliminating variations from
      normal differences in color perception and environmental factors during analysis.
      The image analysis using the parameter hue, for example, has been utilized as a
      highly effective, objective analysis method that correlates with the
      psychological way color is perceived. Hue analysis, however, is best used for
      colorimetric reactions that result in distinct changes from one color to a
      markedly different color and can be inadequate to distinguish between subtle or
      monotonal (colorless-to-colored) color changes. We address this with three unique
      color manipulation (i.e., tinting) techniques that provide greater discrimination
      with such color changes, thus yielding improved limits of detection for various
      colorimetric reactions that may have previously been limited. Tinting is invoked
      through dyeing the reagent substrate, colored printing the device, or colored
      lighting during image capture, and is shown to effectively shift the background
      color of the reaction detection area. Hydrogen peroxide, a constituent of
      peroxide-based explosives, is associated with a monochromatic color change upon
      reaction, and this is used to demonstrate the effectiveness of the tinting
      methods in improving the limit of detection from an undetectable color change to
      0.1 mg mL-1.

PMID- 29068447
TI  - A highly-occupied, single-cell trapping microarray for determination of cell
      membrane permeability.
AB  - Semi- and selective permeability is a fundamentally important characteristic of
      the cell membrane. Membrane permeability can be determined by monitoring the
      volumetric change of cells following exposure to a non-isotonic environment. For
      this purpose, several microfluidic perfusion chambers have been developed
      recently. However, these devices only allow the observation of one single cell or
      a group of cells that may interact with one another in an uncontrolled way. Some
      of these devices have integrated on-chip temperature control to investigate the
      temperature-dependence of membrane permeability, but they inevitably require
      sophisticated fabrication and assembly, and delicate temperature and pressure
      calibration. Therefore, it is highly desirable to design a simple single-cell
      trapping device that allows parallel monitoring of multiple separate, individual
      cells subjected to non-isotonic exposure at various temperatures. In this study,
      we developed a pumpless, single-layer microarray with high trap occupancy of
      single cells. The benchmark performance of the device was conducted by targeting
      spherical particles of 18.8 MUm in diameter as a model, yielding trap occupancy
      of up to 86.8% with a row-to-row shift of 10-30 MUm. It was also revealed that in
      each array the particles larger than a corresponding critical size would be
      excluded by the traps in a deterministic lateral displacement mode. Demonstrating
      the utility of this approach, we used the single-cell trapping device to
      determine the membrane permeability of rat hepatocytes and patient-derived
      circulating tumor cells (Brx-142) at 4, 22 and 37  degrees C. The membrane of rat
      hepatocytes was found to be highly permeable to water and small molecules such as
      DMSO and glycerol, via both lipid- and aquaporin-mediated pathways. Brx-142
      cells, however, displayed lower membrane permeability than rat hepatocytes, which
      was associated with strong coupling of water and DMSO transport but less
      interaction between water and glycerol. The membrane permeability data reported
      here provide new insights into the biophysics of membrane transport such as
      aquaporin expression and coupling transport of water and solutes, as well as
      providing essential data for the ultimate goal of biobanking rare cells and
      precious tissues.

PMID- 29068449
TI  - Heteroleptic complexes via solubility control: examples of Cu(ii), Co(ii), Ni(ii)
      and Mn(ii) complexes based on the derivatives of terpyridine and
      hydroxyquinoline.
AB  - We describe the construction of synthetically challenging heteroleptic complexes
      by capitalizing on the solubility properties of their corresponding favored
      homoleptic complexes. We demonstrate that the formation of a heteroleptic Cu2+
      complex based on 2,2':6',2''-terpyridine (Terpy) and 8-hydroxyquinoline (HQ) is
      not possible due to the insolubility of (HQ)2Cu2+. Replacing HQ with 8-hydroxy-2
      quinolinecarbonitrile (HQCN) enabled the solubility of (HQCN)2Cu2+ in
      acetonitrile, leading to the formation of the heteroleptic complex
      Terpy(HQCN)Cu2+, TQCu. Applying these conditions to the synthesis of the
      corresponding heteroleptic Co2+ complex resulted in TerpyCo2+(acetate)2, which is
      insoluble in acetonitrile. Upon changing the solvent to methanol, the
      carbonitrile group of HQCN was converted to carboxyimidate HQOMe yielding a
      heteroleptic complex Terpy(HQOMe)Co2+, TQ'Co. Using this method, we also
      generated the heteroleptic complex TQ'Ni and the polynuclear heteroleptic complex
      Q'4Q''2Mn4 (Q'' = HQO2Me). Detailed analysis of the complexes included
      characterization by X-ray diffraction, EPR, UV-Vis, high resolution ESI MS, DFT
      calculations and electrochemistry. X-ray analysis of TQCu revealed distorted
      square pyramidal geometry, while TQ'Co and TQ'Ni exhibit distorted octahedral
      geometry, which includes metal coordination via the carboxyimidate nitrogen site.
      Interestingly, Q'4Q''2Mn4 was found to contain a [Mn(MU3-O)2(MU2-O)4N10]2+ core,
      which adopts a distorted octahedral geometry, and two types of HQ chelators.
      Thus, Q'4Q''2Mn4 is also heteroleptic even though it does not contain a Terpy
      ligand. Solution studies revealed that while TQCu is stable in solution, TQ'Co
      and TQ'Ni go through ligand exchange and are partially converted to their
      corresponding homoleptic complexes. Based on these data we could propose a
      mechanism for the formation of TQ'Co and TQ'Ni and show that TQ'Co can be
      prepared directly from Terpy and HQOMe.

PMID- 29068450
TI  - Soy peptide aggregates formed during hydrolysis reduced protein extraction
      without decreasing their nutritional value.
AB  - Upon enzymatic hydrolysis, soy protein isolates showed a strong tendency to
      aggregate, presenting a significant loss of valuable proteins. This study mainly
      focused on the large insoluble aggregates formed during proteolysis, and the
      influence of heating was further explored for a better understanding of the
      mechanism involved. The results from SDS-PAGE and amino acid analysis clearly
      showed that the insoluble aggregates formed upon hydrolysis were aggregated
      peptides, mainly attributed to the hydrophobic interactions between peptides with
      hydrophobic amino acids (Val, Ala, Leu, Ile, Tyr, Phe, and Pro) and sulfur
      containing (Met and Cys) residues. Heating of the hydrolysates further enhanced
      the peptide-protein interactions through hydrophobic forces and disulfide bonds,
      accelerating the aggregation, where fractions from the basic subunits of glycinin
      were particularly involved. Furthermore, taking into consideration the fact that
      aggregates had a high proportion of essential amino acids, the in vitro digestion
      properties of the aggregates were also investigated. Interestingly, the
      relatively pepsin-resistant aggregates showed a high degradability toward
      pancreatin, releasing low molecular weight peptides possessing a higher
      proportion of antioxidative amino acids, which therefore had a better antioxidant
      activity. These results indicated a potential use of the insoluble peptide
      aggregates as protein supplements or active delivery systems for human
      consumption.

PMID- 29068451
TI  - A trans-bidentate bis-pyridinyl ligand with a transition metal hinge.
AB  - A titanocene based metalloligand, Cp*2Ti(C22-py)2, was synthesized and
      coordinated to either Cu(i) or Pd(ii). The metalloligand binds Cu(i) between its
      alkynes and Pd(ii) between its pyridinyl rings, acting as a trans-bidentate
      ligand. In order to bind Pd(ii), significant structural rearrangements were
      necessary, which required the flexibility of the C-Ti-C hinge on the titanocene
      metalloligand.

PMID- 29068452
TI  - Alleviation of oxidative stress-mediated nephropathy by dietary fenugreek
      (Trigonella foenum-graecum) seeds and onion (Allium cepa) in streptozotocin
      induced diabetic rats.
AB  - Oxidative stress plays a major role in the progression of diabetes and the
      pathogenesis of diabetic nephropathy. In this study, the beneficial influence of
      dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) on
      oxidative stress-mediated renal injury was evaluated in streptozotocin-induced
      diabetic rats. Diabetes was induced in adult Wistar rats by the administration of
      streptozotocin (i.p. 45 mg kg-1). Dietary interventions were made with 10%
      fenugreek seeds or 3% onion (freeze-dried) or their combination for 6 weeks.
      These dietary interventions countered nephromegaly in the diabetic animals, the
      increase in creatinine clearance and oxidative stress in renal tissue. These
      dietary interventions significantly countered the increased renal cholesterol and
      triglycerides associated with the diabetic condition. The up-regulation of the
      receptor for advanced glycation end products, inflammatory cytokines and
      oxidative stress markers in the renal tissue of the diabetic rats was effectively
      countered. Renal 8-hydroxy-2-deoxyguanosine, its excretion, DNA fragmentation and
      mitochondrial DNA deletion were significantly annulled in the diabetic rats by
      these dietary interventions. Generally, the beneficial effects were greater in
      the combined intervention, although they were not additive. Thus, the beneficial
      influence of dietary fenugreek and onion on oxidative stress-mediated renal
      injury is higher when consumed together and this may be a strategy to ameliorate
      diabetic nephropathy.

PMID- 29068453
TI  - Orange juice modulates proinflammatory cytokines after high-fat saturated meal
      consumption.
AB  - We aimed to evaluate the postprandial secretion of inflammatory markers induced
      by SFA or MUFA high-fat meal consumption and whether orange juice intake could
      modulate this induction. This study included 55 healthy women (aged 20 to 40
      years): 33 participants received an SFA high-fat meal (~1000 kcal, 37.6% of
      energy intake (E) from SFA) and 22 participants received an MUFA high-fat meal
      (~1000 kcal, 56.3% E from MUFA). Both interventions were accompanied by 500 ml of
      orange juice (test) or water (control). The plasma concentrations of inflammatory
      cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, and TNF-alpha) and CRP
      were determined before (fasting) and 2, 3 and 5 hours after the test meal intake.
      The SFA high-fat meal induced a significant increase in AUC values (for TNF
      alpha, IL-12, IL-10, IL-6 and IL-2 adjusted for baseline concentrations) in
      comparison with MUFA high-fat meal intervention. The results were independent of
      the drink which accompanied the meal (water or orange juice). Both IL-4 and IL
      17A AUC values were significantly increased after an SFA high-fat meal intake,
      accompanied by water, but not by orange juice. In addition, these values were
      higher in relation to MUFA high-fat meal interventions. Also, IL-17A
      significantly increased at 3 h after an SFA high-fat meal intake accompanied by
      water, but not by orange juice. Overall, our conclusions indicate an anti
      inflammatory effect of MUFA compared to SFA high-fat meal intake, while orange
      juice intake was able to mitigate the subclinical increase of postprandial
      inflammation, induced by SFA high-fat meal consumption, for a particular
      biomarker (IL-17A).

PMID- 29068457
TI  - A silver nanoislands on silica spheres platform: enriching trace amounts of
      analytes for ultrasensitive and reproducible SERS detection.
AB  - The performance of surface-enhanced Raman scattering (SERS) for detecting trace
      amounts of analytes depends highly on the enrichment of the diluted analytes into
      a small region that can be detected. A super-hydrophobic delivery (SHD) process
      is an excellent process to enrich even femtomolar analytes for SERS detection.
      However, it is still challenging to easily fabricate a low detection limit, high
      sensitivity and reproducible SHD-SERS substrate. In this article, we present a
      cost-effective and fewer-step method to fabricate a SHD-SERS substrate, named the
      "silver nanoislands on silica spheres" (SNOSS) platform. It is easily prepared
      via the thermal evaporation of silver onto a layer of super-hydrophobic paint,
      which contains single-scale surface-fluorinated silica spheres. The SNOSS
      platform performs reproducible detection, which brings the relative standard
      deviation down to 8.85% and 5.63% for detecting 10-8 M R6G in one spot and spot
      to-spot set-ups, respectively. The coefficient of determination (R2) is 0.9773
      for R6G. The SNOSS platform can be applied to the quantitative detection of
      analytes whose concentrations range from sub-micromolar to femtomolar levels.

PMID- 29068454
TI  - Structure and dynamics of heterometallic clusters derived from addition of metal
      carbonyl fragments to the unsaturated hydride [W2Cp2(MU-H)(MU-PPh2)(NO)2].
AB  - The title complex reacted with [Fe2(CO)9] to give the trinuclear derivative
      [FeW2Cp2(MU-H)(MU-PPh2)(CO)4(NO)2] (W-W = 3.044(1) A) as a result of full
      insertion of the 16-electron Fe(CO)4 fragment into the tricentric W-H-W bond of
      the parent substrate. In contrast, the reactions with the THF adducts
      [M(CO)5(THF)] (M = W, Mo) and [MnCp'(CO)2(THF)] (Cp' = C5H4Me) yielded the MU3
      hydride derivatives [MW2Cp2(MU3-H)(MU-PPh2)(CO)5(NO)2] (W-W = 3.006(1) to
      3.164(1) A for the W3 compound) and [MnW2Cp2Cp'(MU3-H)(MU-PPh2)(CO)2(NO)2]
      respectively, all of them resulting from addition (rather than insertion) of the
      corresponding 16-electron fragment to the W2H moiety of the parent compound.
      Density Functional Theory calculations revealed that edge- and face-bridged
      hydride clusters were of similar energy in the W2Fe system, while the face
      bridged structure was significantly more stable (by more than ca. 40 kJ mol-1)
      for the W3 system. Both clusters displayed fast rearrangement in solution
      involving a flapping movement of the puckered PW2M core of these molecules. This
      was combined, in the W2Fe cluster, with fast exchange between the almost
      isoenergetic edge- and face-bridged hydride isomers. The reactions of the title
      compound with several carbonyl dimers were also examined as an additional
      synthetic approach to the rational synthesis of heterometallic clusters, but were
      unsuccessful except in the case of [Co2(CO)8], which reacted at 253 K in the dark
      to give a mixture of the binuclear complex [CoWCp(MU-PPh2)(CO)4(NO)] (Co-W =
      2.8623(6) A) and the trinuclear cluster [CoW2Cp2(MU-PPh2)(CO)4(NO)2] (W-W =
      3.1654(4) A; W-Co = 2.638(1), 2.829(1) A), the latter resulting from formal
      replacement of the hydride ligand with the 17-electron fragment Co(CO)4, which
      displayed an asymmetric binding to the W2 centre.

PMID- 29068464
TI  - Atomic charges of sulfur in ionic liquids: experiments and calculations.
AB  - Experimental near edge X-ray absorption fine structure (NEXAFS) spectra, X-ray
      photoelectron (XP) spectra and Auger electron spectra are reported for sulfur in
      ionic liquids (ILs) with a range of chemical structures. These values provide
      experimental measures of the atomic charge in each IL and enable the evaluation
      of the suitability of NEXAFS spectroscopy and XPS for probing the relative atomic
      charge of sulfur. In addition, we use Auger electron spectroscopy to show that
      when XPS binding energies differ by less than 0.5 eV, conclusions on atomic
      charge should be treated with caution. Our experimental data provides a benchmark
      for calculations of the atomic charge of sulfur obtained using different methods.
      Atomic charges were computed for lone ions and ion pairs, both in the gas phase
      (GP) and in a solvation model (SMD), with a wide range of ion pair conformers
      considered. Three methods were used to compute the atomic charges: charges from
      the electrostatic potential using a grid based method (ChelpG), natural bond
      orbital (NBO) population analysis and Bader's atoms in molecules (AIM) approach.
      By comparing the experimental and calculated measures of the atomic charge of
      sulfur, we provide an order for the sulfur atoms, ranging from the most negative
      to the most positive atomic charge. Furthermore, we show that both ChelpG and NBO
      are reasonable methods for calculating the atomic charge of sulfur in ILs, based
      on the agreement with both the XPS and NEXAFS spectroscopy results. However, the
      atomic charges of sulfur derived from ChelpG are found to display significant,
      non-physical conformational dependence. Only small differences in individual
      atomic charge of sulfur were observed between lone ion (GP) and ion pair IL(SMD)
      model systems, indicating that ion-ion interactions do not strongly influence
      individual atomic charges.

PMID- 29068465
TI  - Array-comparative genomic hybridization analysis in patients with Mullerian
      fusion anomalies.
AB  - Fusion anomalies of the Mullerian ducts are associated with an increased risk for
      miscarriage and premature labor. In most cases polygenic-multifactorial
      inheritance can be assumed but autosomal-dominant inheritance with reduced
      penetrance and variable manifestation should be considered. We performed array
      comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with
      Mullerian fusion anomalies. In 8 patients we detected microdeletions and
      microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and
      7q31.1. The rearrangement in 17q12 including LHX1 and HNF1beta as well as in
      22q11.21 have already been observed in MRKHS (Mayer-Rokitansky-Kuster-Hauser
      syndrome). In summary, we (1) detected causative micro-rearrangements in patients
      with Mullerian fusion anomalies, (2) show that Mullerian fusion anomalies and
      MRKHS may have a common etiology, and (3) identified new candidate genes for
      Mullerian fusion anomalies.

PMID- 29068466
TI  - Too Much Eukaryote LGT.
AB  - The realization that prokaryotes naturally and frequently disperse genes across
      steep taxonomic boundaries via lateral gene transfer (LGT) gave wings to the idea
      that eukaryotes might do the same. Eukaryotes do acquire genes from mitochondria
      and plastids and they do transfer genes during the process of secondary
      endosymbiosis, the spread of plastids via eukaryotic algal endosymbionts. From
      those observations it, however, does not follow that eukaryotes transfer genes
      either in the same ways as prokaryotes do, or to a quantitatively similar degree.
      An important illustration of the difference is that eukaryotes do not exhibit
      pangenomes, though prokaryotes do. Eukaryotes reveal no detectable cumulative
      effects of LGT, though prokaryotes do. A critical analysis suggests that
      something is deeply amiss with eukaryote LGT theories.

PMID- 29068467
TI  - Understanding the associations and significance of fetal movements in overweight
      or obese pregnant women: a systematic review.
AB  - INTRODUCTION: Presentation with decreased fetal movement (DFM) is associated with
      fetal growth restriction and stillbirth. Some studies report that DFM is frequent
      among overweight or obese mothers. We aimed to determine the significance and
      associations of fetal movements in women of increased body size. MATERIAL AND
      METHODS: This systematic review was conducted in accordance with the PRISMA
      statement and the protocol was registered with PROSPERO (CRD42016046352). Major
      databases were explored from inception to September 2017, using a predefined
      search strategy. We restricted inclusion to studies published in English and
      considered studies of any design that compared fetal movements in women of
      increased and normal body size. Two authors independently extracted data and
      assessed quality. RESULTS: We included 23 publications from 19 observational
      studies; data were extracted from 10 studies. Increased maternal body size was
      not associated with altered perception of fetal movement (four studies, 95 women,
      very low-quality evidence), but was associated with increased presentation for
      DFM (two cohort studies, 20 588 women, OR 1.56, 95% CI 1.27-1.92: three case
      control studies, 3445 women, OR 1.32, 95% CI 1.12-1.54; low-quality evidence).
      Among women with DFM, increased maternal body size was associated with increased
      risk of stillbirth and fetal growth restriction (one study, 2168 women, very low
      quality evidence). CONCLUSIONS: This systematic review identified limited
      evidence that women with increased body size are more likely to present with DFM
      but do not have impaired perception of fetal movements. In women with DFM,
      increased body size is associated with worse pregnancy outcome, including
      stillbirth.

PMID- 29068468
TI  - Expression of the FGFR2c mesenchymal splicing variant in human keratinocytes
      inhibits differentiation and promotes invasion.
AB  - The altered isoform switching of the fibroblast growth factor receptor 2 (FGFR2)
      and aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells is
      involved in cancer progression. We have recently described that the ectopic
      expression of FGFR2c in normal human keratinocytes induces epithelial-mesenchymal
      transition and leads to invasiveness and anchorage-independent growth. Here, we
      extended our analysis to the effects of this FGFR2c forced expression on human
      keratinocyte differentiation and stratification. Our findings demonstrated that,
      differently from cells overexpressing the epithelial splicing variant FGFR2b,
      keratinocytes ectopically expressing FGFR2c are not able to form a monolayer and
      display decreased expression of early differentiation markers. This impaired
      ability to enter the differentiation program is related to the up-modulation of
      the transcription factor DeltaNp63. In addition, FGFR2c-expressing keratinocytes
      undergo defective stratification and invasion of the collagen matrix in 3D
      organotypic cultures, further suggesting their tumorigenic potential. Taken
      together, our results support the hypothesis that the receptor switching and the
      consequent appearance of the mesenchymal FGFR2c variant in the epithelial context
      would drive early steps of carcinogenesis, unbalancing the p63/FGFR interplay,
      and altering the paracrine response to the microenvironment.

PMID- 29068469
TI  - BAG3-dependent expression of Mcl-1 confers resistance of mutant KRAS colon cancer
      cells to the HSP90 inhibitor AUY922.
AB  - Past studies have shown that mutant KRAS colon cancer cells are susceptible to
      apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and
      acquired resistance remains an obstacle for the potential application of the
      inhibitor in the treatment of the disease. Here we report that Mcl-1 is important
      for survival of colon cancer cells in the presence of AUY922. Mcl-1 was
      upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922
      induced apoptosis. This was due to its increased stability mediated by Bcl-2
      associated athanogene domain 3 (BAG3), which was also increased in resistant
      colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic
      endoplasmic reticulum (ER) stress. Functional investigations demonstrated that
      inhibition of Mcl-1, BAG3, or HSF1 triggered apoptosis in resistant colon cancer
      cells, and rendered AUY922-naive colon cancer cells more sensitive to the
      inhibitor. Together, these results identify that the HSF1-BAG3-Mcl-1 signal axis
      is critical for protection of mutant KRAS colon cancer cells from AUY922-induced
      apoptosis, with potential implications for targeting HSF1/BAG3/Mcl-1 to improve
      the efficacy of AUY922 in the treatment of colon cancer.

PMID- 29068470
TI  - Aspartate-beta-semialdeyhyde dehydrogenase as a potential therapeutic target of
      Mycobacterium tuberculosis H37Rv: Evidence from in silico elementary mode
      analysis of biological network model.
AB  - The emergence of multi-drug resistant strains and co-occurrence of tuberculosis
      with HIV creates a major burden to the human health globally. Failure of primary
      antibacterial therapy necessitates the identification of new mycobacterial drugs.
      In this study, a comprehensive analysis involving bottom-up systems biology
      approach was applied wherein we have identified potential therapeutic targets of
      Mycobacterium tuberculosis infections. Our study prioritized M. tuberculosis
      therapeutic targets (aspartate-beta-semialdeyhde dehydrogenase [ASD],
      dihydrodipicolinate reductase and diaminopimelate decarboxylase) based on flux
      and elementary mode analysis using direct mathematical modeling of the relevant
      metabolic pathways. Molecular docking and simulation studies of the priority
      target (ie, ASD) revealed the therapeutic potential of the selected natural
      products (Huperzine A, Rosmarinic acid, and Curcumin) based ASD inhibitors. The
      study highlights the crucial role of systems biology in conjunction with
      molecular interaction (docking) for probing novel leads against an increasingly
      resistant pathogen, M. tuberculousis.

PMID- 29068471
TI  - Long non-coding RNA AGER-1 functionally upregulates the innate immunity gene AGER
      and approximates its anti-tumor effect in lung cancer.
AB  - Little is known about long non-coding RNA (lncRNA) related to innate immunity in
      lung cancer. The advanced glycosylation end-product specific receptor (AGER)
      belongs to the immunoglobulin superfamily, and currently, is the only innate
      immune pattern-recognition receptor whose abnormal expression has been detected
      in lung cancer. We aimed to explore the lncRNA that is related to AGER and test
      its effect on lung carcinogenesis. We selected one lncRNA whose chromosome
      location is in close proximity to AGER namely lnc-AGER-1 (defined as lncAGER).
      The expression of lncAGER was tested in 276 pairs of lung cancer tissues and
      adjacent lung normal tissues, and its correlation with lung cancer clinical
      progress was analyzed. A series of assays were further used to assess the
      biological function of lncAGER on lung cancer development, tumor immunity and
      autophagy. LncAGER expression was moderately correlated with AGER expression (r =
      0.360, P = 2.15 * 10-18 ) underlying a mechanism that lncAGER upregulates AGER by
      competitively binding to miRNA-185. LncAGER was significantly down-regulated in
      76.4% of lung cancer tissues compared to adjacent normal tissues due to promoter
      hypermethylation. Over-expression of the lncRNA resulted in significant decreases
      in proliferation rate, migration ability, colony formation efficiency of lung
      cancer cells and tumor growth in nude mice. Notably, lncAGER possibly conduced to
      enhancement of cytotoxic effect of THP1. Additionally, the lncRNA also promoted
      cell apoptosis by strengthening autophagy. Taken together, these observations
      suggest that lncAGER has an inhibitory effect on lung cancer development via
      AGER, which may serve as a target for lung cancer treatment.

PMID- 29068472
TI  - Factors affecting the dissipation of pharmaceuticals in freshwater sediments.
AB  - Degradation is one of the key processes governing the impact of pharmaceuticals
      in the aquatic environment. Most studies on the degradation of pharmaceuticals
      have focused on soil and sludge, with fewer exploring persistence in aquatic
      sediments. We investigated the dissipation of 6 pharmaceuticals from different
      therapeutic classes in a range of sediment types. Dissipation of each
      pharmaceutical was found to follow first-order exponential decay. Half-lives in
      the sediments ranged from 9.5 (atenolol) to 78.8 (amitriptyline) d. Under sterile
      conditions, the persistence of pharmaceuticals was considerably longer. Stepwise
      multiple linear regression analysis was performed to explore the relationships
      between half-lives of the pharmaceuticals, sediment physicochemical properties,
      and sorption coefficients for the compounds. Sediment clay, silt, and organic
      carbon content and microbial activity were the predominant factors related to the
      degradation rates of diltiazem, cimetidine, and ranitidine. Regression analysis
      failed to highlight a key property which may be responsible for observed
      differences in the degradation of the other pharmaceuticals. The present results
      suggest that the degradation rate of pharmaceuticals in sediments is determined
      by different factors and processes and does not exclusively depend on a single
      sediment parameter. Environ Toxicol Chem 2018;37:829-838. (c) 2017 SETAC.

PMID- 29068473
TI  - Anaerobic biotransformation of N-methyl perfluorobutanesulfonamido ethanol and N
      ethyl perfluorooctanesulfonamido ethanol.
AB  - Some fluorochemical products are manufactured using N-methyl
      perfluorobutanesulfonamido ethanol (MeFBSE), a short-chain replacement for
      perfluorooctyl-based chemistries N-methyl and N-ethyl perfluorooctanesulfonamido
      ethanols (EtFOSE). The present study shows for the first time the anaerobic
      biodegradation of MeFBSE and EtFOSE in municipal digester sludge under
      methanogenic conditions. Both MeFBSE and EtFOSE were incubated for 108 d with
      anaerobic digester sludge. Although sterile controls did not remove MeFBSE, it
      was degraded in live sludge. The loss of MeFBSE coincided with production of N
      methyl perfluorobutanesulfonamido acetate (MeFBSAA) and perfluorobutane sulfinate
      (PFBSI). The biodegradation appeared biphasic, with pseudo first-order loss
      between days 0 and 70, resulting in approximately 75% removal but no further
      depletion of MeFBSE between days 70 and 108. By day 108 MeFBSAA and PFBSI
      accounted for 57 and 40 mol% of initial dose, respectively. Mass balance values
      in live cultures on days 0, 10, 21, 29, 70, and 108 were 103, 92, 94, 100, 93,
      and 122%, respectively. The apparent first-order biodegradation rate constant for
      MeFBSE over the first 70 d was 0.0194 d-1 , and the apparent half-life was 35.8
      d. Incubation of EtFOSE with live digester sludge resulted in low-level formation
      of N-ethyl perfluorooctane-sulfonamido acetate and perfluorooctane sulfinate,
      which did not form in sterile controls. Although it was not measurably lost, 2 to
      3% loss of EtFOSE was calculated based on product concentrations. The total
      product formation rate constant was determined by first-order kinetic evaluation
      over the first 72 d to estimate a first-order biodegradation rate constant for
      EtFOSE at 0.000374 d-1 , and the apparent half-life time was 1860 d. Environ
      Toxicol Chem 2018;37:768-779. (c) 2017 SETAC.

PMID- 29068476
TI  - Suppression of long non-coding RNA LET potentiates bone marrow-derived
      mesenchymal stem cells (BMSCs) proliferation by up-regulating TGF-beta1.
AB  - Long non coding RNAs (lncRNAs) show an encouraging trend in regulating the
      proliferation of bone marrow-derived mesenchymal stromal cells (BMSCs). The
      present study investigated the role of lncRNA low expression in tumor (LET) in
      BMSCs proliferation. Our result showed that LET was down-regulated in rapidly
      proliferated BMSCs (P < 0.05). Suppression of LET promoted BMSCs proliferation
      and over-expression of LET inhibited BMSCs proliferation (P < 0.05). LET
      negatively regulated the expression of transforming growth factor beta1 (TGF
      beta1) in BMSCs (P < 0.05). Knockdown of TGF-beta1 reversed the LET suppression
      induced BMSCs proliferation (P < 0.05). Moreover, knockdown of TGF-beta1
      alleviated the LET suppression-induced activation of Wnt/beta-catenin pathway in
      BMSCs. Therefore, we drew the conclusion that LET suppression promoted BMSCs
      proliferation by up-regulating the expression of TGF-beta1 and activating
      Wnt/beta-catenin pathway.

PMID- 29068474
TI  - The PI3K/AKT signaling pathway: Associations of miRNAs with dysregulated gene
      expression in colorectal cancer.
AB  - The PI3K/AKT-signaling pathway is one of the most frequently activated signal
      transduction pathways in cancer. We examined how dysregulated gene expression is
      associated with miRNA expression in this pathway in colorectal cancer (CRC). We
      used data from 217 CRC cases to evaluate differential pathway gene expression
      between paired carcinoma and normal mucosa and identify miRNAs that are
      associated with these genes. Gene expression data from RNA-Seq and miRNA
      expression data from Agilent Human miRNA Microarray V19.0 were analyzed. We
      focused on genes most associated with CRC (fold change (FC) of >1.5 or <0.67)
      that were statistically significant after adjustment for multiple comparisons. Of
      the 304 genes evaluated, 76 had a FC of <0.67, and 57 had a FC of >1.50; 47 of
      these genes were associated with miRNA differential expression. There were 145
      mRNA:miRNA seed-region matches of which 26 were inversely associated suggesting a
      greater likelihood of a direct association. Most miRNA:mRNA associations were
      with factors that stimulated the pathway. For instance, both IL6R and PDGFRA had
      inverse seed-region matches with seven miRNAs, suggesting that these miRNAs have
      a direct effect on these genes and may be key elements in activation of the
      pathway. Other miRNA:mRNA associations with similar impact on the pathway were
      miR-203a with ITGA4, miR-6071 with ITGAV, and miR-375 with THBS2, all genes
      involved in extracellular matrix function that activate PI3Ks. Gene expression in
      the PI3K/Akt-signaling pathway is dysregulated in CRC. MiRNAs were associated
      with many of these dysregulated genes either directly or in an indirect manner.

PMID- 29068475
TI  - Genetically Determined Later Puberty Impacts Lowered Bone Mineral Density in
      Childhood and Adulthood.
AB  - Later puberty associates with lower areal bone mineral density (aBMD), and both
      are risk factors for osteoporosis. However, the association between puberty
      timing-associated genetic variants and aBMD during development, and the causal
      relationship between puberty timing and aBMD, remain uncharacterized. We
      constructed sex-specific polygenic risk scores (GRS) consisting of 333 genetic
      variants associated with later puberty in European-descent children in the Bone
      Mineral Density in Childhood Study (BMDCS), consisting of a longitudinal cohort
      with up to seven assessments (n = 933) and a cross-sectional cohort (n = 486).
      These GRS were tested for associations with age- and sex-specific aBMD Z-scores
      at the lumbar spine (LS), femoral neck (FN), total hip, and distal radius,
      accounting for clinical covariates using sex-stratified linear mixed models. The
      causal relationship between puberty timing and aBMD was tested in the BMDCS and
      in publicly available adult data (GEFOS consortium) using two-sample Mendelian
      randomization (MR). The puberty-delaying GRS was associated with later puberty
      and lower LS-aBMD in the BMDCS in both sexes (combined beta +/- SE = -0.078 +/-
      0.024; p = 0.0010). In the MR framework, the puberty-delaying genetic instrument
      also supported a causal association with lower LS-aBMD and FN-aBMD in adults of
      both sexes. Our results suggest that pubertal timing is causal for diminished
      aBMD in a skeletal site- and sex-specific manner that tracks throughout life,
      potentially impacting later risk for osteoporosis, which should be tested in
      future studies. (c) 2017 American Society for Bone and Mineral Research.

PMID- 29068479
TI  - Genetic profile and mutation spectrum of Leber congenital amaurosis in a larger
      Indian cohort using high throughput targeted re-sequencing.
AB  - To provide a comprehensive data on the prevalence of mutations in Leber
      congenital amaurosis (LCA) candidate genes from a larger Indian cohort. Ninety
      two unrelated subjects were recruited after complete ophthalmic examination and
      informed consent. Targeted re-sequencing of 20 candidate genes was performed
      using Agilent HaloPlex target enrichment assay and sequenced on Illumina MiSeq
      platform. The data were analyzed using standard bioinformatics pipeline, variants
      annotated, validated and segregated. Genotype-phenotype correlation was performed
      for the mutation-positive cases. Targeted next generation sequencing (NGS) for
      the 20 candidate genes generated data with an average sequence coverage and depth
      of 99.03% and 134X, respectively. Mutations were identified in 61% (56/92) of the
      cases, which were validated, segregated in the families and absent in 200 control
      chromosomes. These mutations were observed in 14/20 candidate genes and 39%
      (21/53) were novel. Distinct phenotypes were observed with respect to genotypes.
      To our knowledge, this study presents the first comprehensive mutation spectrum
      of LCA in a large Indian cohort. The mutation-negative cases indicate scope for
      finding novel candidate gene(s) although mutations in deep intronic and
      regulatory regions cannot be ruled out.

PMID- 29068478
TI  - Matrix metallopeptidase 9 targeted by hsa-miR-494 promotes silybin-inhibited
      osteosarcoma.
AB  - Osteosarcoma (OS) is the most common malignant tumor that develops in bone. Its
      mortality is very high. Therefore, study of mechanisms of pathogenesis of the OS
      is urgently required. Previous studies of microarray showed that the expression
      levels of matrix metallopeptidase 9 (MMP-9) altered significantly in OS. In
      addition, overexpression of MMP-9 is recognized as an indicator in cancer.
      However, the exact roles of MMP-9 in OS are not fully investigated. Thus, we
      firstly studied the roles of MMP-9 in OS and revealed that silence of MMP-9
      inhibited OS cell proliferation as determined by MTT assay and colony formation
      assay. Secondly, we conducted TUNEL assay and confirmed loss of functions of MMP
      9 induced OS cell apoptosis. Next, we used lentivector packaging method to
      overexpress MMP-9 and found that overexpression of MMP-9 promoted OS cell
      migration. Fourthly, the results of luciferase assay showed that MMP-9 was
      targeted by hsa-miR-494, which inhibited OS. Fifthly, we revealed that the levels
      of hsa-miR-494 were upregulated by the drug silybin which inhibited OS. Finally,
      we revealed that silybin inhibited OS cell viability by altering the protein
      levels of beta-catenin and Runt-related transcription factor 2 (RUNX2) as
      determined by western blot and immunocytochemistry (ICC).

PMID- 29068480
TI  - Phlpp inhibitors block pain and cartilage degradation associated with
      osteoarthritis.
AB  - Phlpp protein phosphatases are abnormally abundant within human osteoarthritic
      articular chondrocytes and may contribute to the development of osteoarthritis.
      Mice lacking Phlpp1 were previously shown to be resistant to post-traumatic
      osteoarthritis. Here a small molecule with therapeutic properties that inhibits
      Phlpp1 and Phlpp2 was tested for its ability to slow post-traumatic OA in mice
      and to stimulate anabolic pathways in human articular cartilage from OA joints.
      PTOA was induced in male C57Bl/6 mice by surgically destabilizing the meniscus.
      Seven weeks after surgery, mice received a single intra-articular injection of
      the Phlpp inhibitor NSC117079 or saline. Mechanical allodynia was measured with
      von Frey assays, mobility was tracked in an open field system, and cartilage
      damage was assessed histologically. A single intra-articular injection of the
      Phlpp inhibitor NSC117079 attenuated mechanical allodynia and slowed articular
      cartilage degradation in joints with a destabilized meniscus. Animals treated
      with the Phlpp inhibitor 7 weeks after injury maintained normal activity levels,
      while those in the control group traveled shorter distances and were less active
      3 months after the joint injury. NSC117079 also increased production of cartilage
      extracellular matrix components (glycosaminoglycans and aggrecan) in over 90% of
      human articular cartilage explants from OA patients and increased phosphorylation
      of Phlpp1 substrates (AKT2, ERK1/2, and PKC) in human articular chondrocytes. Our
      results indicate that Phlpp inhibitor NSC117079 is a novel osteoarthritis disease
      modifying drug candidate that may have palliative affects. (c) 2017 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1487-1497,
      2018.

PMID- 29068481
TI  - Hypophosphatemia, Severe Bone Pain, Gait Disturbance, and Fatigue Fractures After
      Iron Substitution in Inflammatory Bowel Disease: A Case Report.
AB  - Intravenous infusions of different iron formulations are recognized as a cause of
      hypophosphatemia. Chronic hypophosphatemia can alter bone metabolism and bone
      material structure. As a consequence, osteomalacia may develop and lead to bone
      fragility. Herein, we report a patient with Crohn's disease presenting with
      persistent hypophosphatemia and insufficiency fractures while receiving regular
      iron infusions due to chronic gastrointestinal bleeding. Previously, the patient
      regularly received vitamin D and also zoledronic acid. The patient underwent bone
      biopsy of the iliac crest that showed typical signs of osteomalacia with
      dramatically increased osteoid volume and decreased bone formation. Analysis of
      the bone mineralization density distribution (BMDD) revealed a more complex
      picture: On the one hand, there was a shift to higher matrix mineralization,
      presumably owing to low bone turnover; on the other hand, a broadening of the
      BMDD indicating more heterogeneous mineralization due to osteomalacia was also
      evident. This is the first report on changes of bone histomorphometry and bone
      matrix mineralization in iron-induced osteomalacia. (c) 2017 American Society for
      Bone and Mineral Research.

PMID- 29068482
TI  - Degradation alters the lubrication of articular cartilage by high viscosity,
      hyaluronic acid-based lubricants.
AB  - Hyaluronic acid (HA) is widely injected as a viscosupplement in the treatment of
      osteoarthritis. Despite its extensive use, it is not currently known if cartilage
      degradation alters how HA-based solutions lubricate the articular surface. In
      this study we utilized a model of cartilage degradation by IL-1beta along with a
      recently developed framework to study role of cartilage degradation on
      lubrication by clinically-approved HA-based lubricants with high viscosities.
      Cartilage explants were cultured up to 8 days with 10 ng/ml IL-1beta. After
      culture, samples were examined histologically, immunohistochemically,
      biochemically, mechanically, topographically, and tribologically. The
      tribological testing analyzed both boundary and mixed lubrication modes to assess
      individual effects of viscosity and boundary lubricating ability. Friction
      testing was carried out using PBS and two clinically approved HA-based
      viscosupplements in a cartilage-glass configuration. After culture with IL-1beta,
      boundary mode friction was elevated after both 4 and 8 days. Additionally,
      friction in mixed mode lubrication, where HA is most effective as a lubricant,
      was significantly elevated after 8 days of culture. As cartilage became rougher,
      softer, and more permeable after culture, the boundary mode plateau was extended,
      and as a result, significantly increased lubricant viscosities or sliding speeds
      were necessary to achieve effective mixed lubrication. Overall, this study
      revealed that lubrication of cartilage by HA is degradation-dependent and
      coincides with changes in mechanics and roughness. (c) 2017 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1456-1464, 2018.

PMID- 29068483
TI  - Supraphysiological loading induces osteocyte-mediated osteoclastogenesis in a
      novel in vitro model for bone implant loosening.
AB  - We aimed to develop an in vitro model for bone implant loosening, allowing
      analysis of biophysical and biological parameters contributing to mechanical
      instability-induced osteoclast differentiation and peri-implant bone loss. MLO-Y4
      osteocytes were mechanically stimulated for 1 h by fluid shear stress using
      regimes simulating: (i) supraphysiological loading in the peri-prosthetic
      interface (2.9 +/- 2.9 Pa, 1 Hz, square wave); (ii) physiologic loading in the
      cortical bone (0.7 +/- 0.7 Pa, 5 Hz, sinusoidal wave); and (iii) stress
      shielding. Cellular morphological parameters, membrane-bound RANKL expression,
      gene expression influencing osteoclast differentiation, nitric oxide release and
      caspase 3/7-activity were determined. Either Mouse bone marrow cells were
      cultured on top of loaded osteocytes or osteocyte-conditioned medium was added to
      bone marrow cells. Osteoclast differentiation was assessed after 6 days. We found
      that osteocytes subjected to supraphysiological loading showed similar morphology
      and caspase 3/7-activity compared to simulated physiological loading or stress
      shielding. Supraphysiological stimulation of osteocytes enhanced osteoclast
      differentiation by 1.9-fold compared to physiological loading when cell-to-cell
      contact was permitted. In addition, it enhanced the number of osteoclasts using
      conditioned medium by 1.7-fold, membrane-bound RANKL by 3.3-fold, and nitric
      oxide production by 3.2-fold. The stimulatory effect of supraphysiological
      loading on membrane-bound RANKL and nitric oxide production was higher than that
      achieved by stress shielding. In conclusion, the in vitro model developed
      recapitulated the catabolic biological situation in the peri-prosthetic interface
      during instability that is associated with osteoclast differentiation and
      enhanced RANKL expression. The model thus provides a platform for pre-clinical
      testing of pharmacological interventions with potential to stop instability
      induced bone implant loosening. (c) 2017 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:1425-1434, 2018.

PMID- 29068485
TI  - Is the hygiene hypothesis relevant for the risk of multiple sclerosis?
AB  - The hygiene hypothesis, suggesting that low exposure to pathogens early in life
      can increase the risk for immune-mediated diseases, has been proposed as an
      explanation for the increase in incidence of allergy and autoimmune diseases in
      industrialized countries during the last decades. Several aspects of the hygiene
      hypothesis have been related to MS. Already in 1966, the risk of MS was suggested
      to be higher in individuals with high hygienic standard during childhood.
      Further, an episode of infectious mononucleosis is an independent risk factor for
      MS and can be regarded as an indicator of low exposure to pathogens early in
      life, as infection with Epstein-Barr virus often is asymptomatic when it occurs
      in young children. Conflicting results have been reported regarding number of
      siblings, attendance in a day care center and exposure to animals during
      childhood in relation to MS risk, but common childhood infections and
      vaccinations do not seem to influence the risk of MS. In line with the hygiene
      hypothesis, two large meta-analyses have recently shown that infection with
      Helicobacter pylori is negatively correlated with MS. Moreover, a protective
      influence of helminth infection on MS has been observed in several, small
      clinical studies, but more knowledge is needed before a potential role of
      helminth-derived therapy in MS is determined. Also, it has been hypothesized that
      infection with the parasite Toxoplasma gondii could be protective against MS.

PMID- 29068484
TI  - The clinical utility of JC virus antibody index measurements in the context of
      progressive multifocal leukoencephalopathy.
AB  - In natalizumab-treated patients without previous immunosuppressive treatment, the
      JCV antibody index is used to stratify PML risk. A high index value indicates
      that the risk to develop PML is significantly elevated, although probably about
      99% of patients with this index value will not develop PML. This minireview aimed
      to provide an overview of the basic virology and immunology relevant to
      understanding JCV infections in MS patients, with a focus on what is presently
      known about antibodies to JCV and how they could be of use to predict and
      diagnose PML.

PMID- 29068486
TI  - Vaccines and multiple sclerosis.
AB  - An association between certain vaccinations and onset or relapse of multiple
      sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature
      review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON).
      Case studies were excluded. With the exception of a live vaccine against yellow
      fever, vaccinations appear safe in untreated patients with MS and ON. However,
      most studies were underpowered, and small risks cannot be excluded. One study of
      BCG vaccination after the first demyelinating event showed even a reduced risk of
      developing MS. Further studies are needed to fully exclude a causal association.

PMID- 29068487
TI  - Nature, nurture, and microbes: The development of multiple sclerosis.
AB  - This paper argues that multiple sclerosis (MS) is the result of an autoimmune
      attack against components of the central nervous system (CNS). The effector cells
      involved in the pathogenic process are CNS-autoreactive T cells present in the
      healthy immune system in a resting state. Upon activation, these cells cross the
      blood-brain barrier and attack the CNS target tissue. Recent evidence indicates
      that autoimmune activation may happen in the intestine, following an interaction
      of bacterial components of the gut flora with local CNS autoreactive T cells. The
      consequences of this concept are discussed.

PMID- 29068488
TI  - Human endogenous retroviruses in the aetiology of MS.
AB  - Several lines of investigation have provided strong indications for an
      association between the immune-mediated, neurologic disease multiple sclerosis
      (MS) and human endogenous retroviruses (HERVs). Whether the relationship is
      causal is yet to be established. Endogenous retroviruses are pathogenic-in other
      species than the human. Several aspects of the activation and involvement of
      specific HERV families (HERV-H/F and HERV-W/MSRV) have been documented, both for
      cells in the periphery and in the central nervous system. Specific HERV-encoded
      genes and certain gene products (envelope proteins, Envs) appear strongly
      associated with the disease and have pathogenic potential. Most HERV sequences
      are non-functional, whereas some HERV loci have coding potential but remain
      quiescent in non-pathological conditions, so the importance of regulatory
      pathways and epigenetics involved in regulating HERV activation, de-repression,
      and also involvement of retroviral restriction factors, is emerging. Disease
      intervention by means of antiretrovirals has potential as a novel therapeutic
      strategy in MS treatment; this is compounded by the apparently reduced risk of MS
      in HIV infection as a consequence of therapy. Extensive studies of HERVs, their
      role in neurologic diseases, and their potential as therapeutic targets are
      needed.

PMID- 29068489
TI  - Preface.

PMID- 29068490
TI  - Infections in patients with multiple sclerosis: Implications for disease
      modifying therapy.
AB  - Patients with multiple sclerosis have an increased risk of infections compared to
      the general population. The increased risk has been described for decades and is
      not alone attributed to the use of disease-modifying drugs, but secondary to the
      disability. The introduction of more potent immunomodulatory drugs may cause an
      additional challenge, and depending on the mechanism of action, a treatment
      induced increased risk of bacterial, viral, fungal or parasitic infections is
      observed. The choice of treatment in the individual patient with infections and
      multiple sclerosis must be guided by the drugs' specific mechanism of action, the
      drug-specific risk of infection and comorbidities. Increased monitoring and
      follow-up through treatment registries is warranted to increase our understanding
      and thereby improve management.

PMID- 29068491
TI  - MS and infections-Abandoned and surviving hypotheses.
AB  - In this introduction, we follow the ups and downs of infections in MS
      pathogenesis. Our arguments focus on specific agents and events, not referring to
      general MS epidemiology. The historical approach continues on to contemporary
      data and a critical analysis.

PMID- 29068492
TI  - Trials of antivirals in the treatment of multiple sclerosis.
AB  - There is increasing evidence that human herpes viruses and human endogenous
      retroviruses (HERV) are involved in the aetiology and pathogenesis of multiple
      sclerosis (MS). In order to acquire the ultimate evidence to confirm such a
      relationship, it is probably required to use specific antiviral drugs in clinical
      trials of MS. The results of published antiviral clinical trials in patients with
      MS are summarized in this review. None of them showed statistically significant
      effects on primary outcomes of disease activity or on disability development.
      However, given their small sample sizes, the strong trends and effects observed
      in subgroup analysis of antiherpes virus treatment in patients with MS warrant
      further studies. The possible involvement of HERV in MS is intriguing, and drugs
      have been developed that could reduce the impact of HERV in MS. However, larger
      studies are needed as the phase I and II trials were not designed to show
      clinical efficacy in MS.

PMID- 29068493
TI  - Managing Epstein-Barr virus and other risk factors in MS-Future perspectives.
AB  - Here, we discuss the rationale and feasibility of treatment directed against the
      modifiable risk factors in multiple sclerosis. The established environmental risk
      factors vitamin D insufficiency, cigarette smoke exposure, adolescence
      overweight, and Epstein-Barr virus infection are reviewed. Already available
      measures to target these risk factors are discussed.

PMID- 29068494
TI  - Fluid biomarkers for microglial activation and axonal injury in multiple
      sclerosis.
AB  - Although it is clear that the immune system is an important disease driver in
      multiple sclerosis (MS), it is presently unknown what initiates the process.
      Infections have been mentioned as potential triggers, which is specifically dealt
      with in other articles of this volume. Here, I give an overview of two fluid
      biomarkers that reflect key elements of the MS process: microglial activation
      (cerebrospinal fluid [CSF] sTREM2) and axonal injury (CSF and serum/plasma
      neurofilament light). I review recent data on how these markers are altered in
      MS, how they change in relation to disease progression and treatment and,
      finally, how they can be used as tools in MS research.

PMID- 29068495
TI  - Infections in MS: An innate immunity perspective.
AB  - Multiple sclerosis is a multifaceted inflammatory-autoimmune disease, which shows
      remarkable heterogeneity in its clinical presentation, disease progression and in
      tissue lesions in the CNS. Focal lesions in white matter consist of immune
      effector cells, antibodies, and complement deposits in varying combinations,
      suggesting that immune mechanisms related to CNS pathology are multiple. Although
      adaptive immunity to myelin antigens is essential in MS pathogenesis, innate
      immune mechanisms are likely involved in its initiation and perpetuation. One key
      question is if recognition of infectious agents and microbial products by innate
      immune mechanisms impacts on MS and if so, how and where? This short review aims
      at conceptualizing how interactions between microbes and innate immune mechanisms
      could contribute to MS pathogenesis. Consideration is given to initiation of
      local inflammation and to myelin-specific immune responses, and how innate
      immunity and microbes may contribute to these. Recent advances in our
      understanding of lymphatic drainage of CNS, its immune surveillance and effects
      of gut microbiota and obesity on systemic endotoxin levels and T-cell priming may
      open new perspectives to understanding the roles that infectious agents and
      microbes may have in MS.

PMID- 29068497
TI  - Leveraging natural capital to solve the shared education and conservation crisis.

PMID- 29068496
TI  - Effectiveness of Oral Bisphosphonates in Reducing Fracture Risk Among Oral
      Glucocorticoid Users: Three Matched Cohort Analyses.
AB  - The benefit of oral bisphosphonates in reducing fracture risk in glucocorticoid
      induced osteoporosis is controversial. We aimed to estimate the effectiveness of
      oral bisphosphonates in reducing fracture risk in a cohort of new chronic oral
      glucocorticoid users. We created three matched cohorts using health care
      administrative data from Ontario, Canada. We included residents aged 66 years and
      older initiating chronic oral glucocorticoids (>=450 mg prednisone equivalent and
      >=2 glucocorticoid prescriptions within a 6-month window) between January 1998
      and September 2014. Exposed patients were those who initiated an oral
      bisphosphonate (alendronate, etidronate, or risedronate) within the first 6
      months of starting chronic oral glucocorticoid therapy. Exposed cohorts (3945
      alendronate, 5825 risedronate, and 8464 etidronate) were each matched 1:1 to
      unexposed patients on glucocorticoid exposure, fracture risk factors, and
      propensity score. We examined incident hip (primary outcome), vertebral, forearm,
      and humerus fractures using Cox proportional hazard models. Alendronate (hazard
      ratio [HR] = 0.46, 95% confidence interval [CI] 0.25-0.80) and risedronate (HR =
      0.58, 95% CI 0.36-0.90) were associated with reduced hip fracture risk.
      Alendronate (HR =  0.52, 95% CI 0.39-0.68), etidronate (HR = 0.59, 95% CI 0.48
      0.73) and risedronate (HR = 0.47 95% CI 0.36-0.60) were associated with reduced
      vertebral fracture risk. No risk reduction in forearm or humerus fractures was
      apparent for any bisphosphonate. Among older chronic glucocorticoid initiators,
      all oral bisphosphonates reduced vertebral fracture risk, yet only alendronate
      and risedronate reduced hip fracture risk. Results were similar between men and
      women. We provided compelling evidence that early initiation of oral
      bisphosphonates during chronic oral glucocorticoid therapy is beneficial to
      prevent osteoporotic fractures. (c) 2017 American Society for Bone and Mineral
      Research.

PMID- 29068498
TI  - Use of prospective and retrospective risk assessment methods that simplify
      chemical mixtures associated with treated domestic wastewater discharges.
AB  - A framework is presented that is intended to facilitate the evaluation of
      potential aquatic ecological risks resulting from discharges of down-the-drain
      chemicals. A scenario is presented using representatives of many of the types of
      chemicals that are treated domestically. Predicted environmental chemical
      concentrations are based on reported loading rates and routine removal rates for
      3 types of treatment: trickling filter, activated sludge secondary treatment, and
      activated sludge plus advanced oxidation process as well as instream effluent
      dilution. In tier I, predicted effluent concentrations were compared with the
      lowest predicted-no-effect concentration (PNEC) obtained from the literature
      using safety factors as needed. A cumulative risk characterization ratio (cumRCR)
      < 1.0 indicates that risk is unlikely and no further action is needed. Otherwise,
      a tier 2 assessment is used, in which PNECs are based on trophic level. If tier 2
      indicates a possible risk, then a retrospective assessment is recommended. In
      tier 1, the cumRCR was > 1.0 for all 3 treatment types in our scenario, even
      though no chemical exceeded a hazard quotient of 1.0 in activated sludge or
      advanced oxidation process. In tier 2, activated sludge yielded a lower cumRCR
      than trickling filter because of higher removal rates, and the cumRCR in the
      advanced oxidation process was << 1.0. Based on the maximum cumulative risk ratio
      (MCR), more than one-third of the predicted risk was accounted for by one
      chemical, and at least 90% was accounted for by 3 chemicals, indicating that few
      chemicals influenced the mixture risk in our scenario. We show how a
      retrospective assessment can test whether certain chemicals hypothesized as
      potential drivers in the prospective assessment could have, or are having,
      deleterious effects on aquatic life. Environ Toxicol Chem 2018;37:690-702. (c)
      2017 The Authors. Environmental Toxicology and Chemistry Published by Wiley
      Periodicals, Inc. on behalf of SETAC.

PMID- 29068499
TI  - Changes in paced signals may predict in-hospital cardiac arrest.
AB  - BACKGROUND: An increasing number of patients with chronic illnesses have
      implanted cardiac rhythm devices such as pacemakers and implantable cardioverter
      defibrillators (ICDs). This study was conducted to identify potentially useful
      predictors of in-hospital cardiac arrest (I-HCA) within paced electrocardiogram
      (ECG) signals from cardiovascular patients with implanted medical devices.
      METHODS: In this retrospective study of 17 subjects, full-disclosure ECG traces
      prior to the time of documented I-HCA were analyzed to determine R-R intervals
      and QRS durations (QRSd). RESULTS: Ventricular paced QRSd prolongation was
      observed prior to I-HCA in 10/16 (63%) subjects. QRSd was significantly greater
      immediately preceding cardiac arrest than during each of the 8 hours prior to
      cardiac arrest (P < 0.05). Heart rate changes (measured using standard deviation)
      within 15 minutes of cardiac arrest were significantly greater in subjects with
      pulseless electrical activity (PEA)/asystolic arrest compared to those with
      cardiac arrests due to ventricular tachycardia/ventricular fibrillation (VT/VF)
      (10.13 vs 3.31; P  =  0.024). Significant differences over the 8 hours preceding
      cardiac arrest in heart rate (74 vs 86 beats/min; P  =  0.002) and QRS duration
      (172 ms vs 137 ms; P < 0.001) were observed between subjects with initial rhythms
      of VT/VF and those with initial rhythms of PEA/asystole. CONCLUSIONS: Patterns of
      diagnostic ECG features can be extracted from the telemetry data of patients with
      implanted medical devices prior to adverse events including I-HCA. The detection
      of these significant changes might have an immediate prognostic impact on the
      timely treatment of some patients at risk of adverse events.

PMID- 29068500
TI  - What would Dr. James parkinson think today? Mutations in beta-glucocerebrosidase
      and risk of Parkinson's disease.

PMID- 29068501
TI  - Erratum.

PMID- 29068502
TI  - Utilising Sodium-Mediated Ferration for Regioselective Functionalisation of
      Fluoroarenes via C-H and C-F Bond Activations.
AB  - Pairing iron bis(amide) Fe(HMDS)2 with Na(HMDS) to form new sodium ferrate base
      [(dioxane)0.5 ?NaFe(HMDS)3 ] (1) enables regioselective mono and di-ferration
      (via direct Fe-H exchange) of a wide range of fluoroaromatic substrates under
      mild reaction conditions. Trapping of several ferrated intermediates has provided
      key insight into how synchronised Na/Fe cooperation operates in these
      transformations. Furthermore, using excess 1 at 80  degrees C switches on a
      remarkable cascade process inducing the collective twofold C-H/threefold C-F bond
      activations, where each C-H bond is transformed to a C-Fe bond whereas each C-F
      bond is transformed into a C-N bond.

PMID- 29068503
TI  - Increasing the Reactivity of Diborenes: Derivatization of NHC-Supported
      Dithienyldiborenes with Electron-Donor Groups.
AB  - A series of NHC-supported 1,2-dithienyldiborenes was synthesized from the
      corresponding (dihalo)thienylborane NHC precursors. NMR and UV/Vis spectroscopic
      data, as well as X-ray crystallographic analyses, were used to assess the
      electronic and steric influences on the B=B double bond of various NHCs and
      electron-donating substituents on the thienyl ligands. Crystallographic data
      showed that the degree of coplanarity of the diborene core and thienyl groups is
      highly dependent on the sterics of the substituents. Furthermore, any increase in
      the electron-donating ability of the substituents resulted in the destabilization
      of the HOMO and greater instability of the resulting diborenes.

PMID- 29068504
TI  - Lewis Acid-Catalyzed Intramolecular [3+2] Cross-Cycloaddition of Aziridine 2,2
      Diesters with Conjugated Dienes for Construction of Aza-[n.2.1] Skeletons.
AB  - A novel Lewis acid-catalyzed [3+2] intramolecular cross-cycloaddition (IMCC)
      between aziridine 2,2-diesters and conjugated dienes has been developed. This is
      the first regiospecific IMCC of intramolecular 1,3-dipolar cycloadditions of
      azomethine ylides with carbon=carbon double bonds, and supplies a general and
      efficient strategy for construction of structurally complex and diverse aza
      [n.2.1] skeletons. The [3+2]IMCC could be carried out under mild conditions and
      in gram scale. More importantly, 3-alkyl-substituted aziridines were also
      successful. The excellent structural diversity, the facile operation and the
      versatile post-modifications will support the applications of the [3+2]IMCC in
      natural products synthesis and drugs discovery.

PMID- 29068506
TI  - Click Chemistry: Novel Applications in Cell Biology and Drug Discovery.
AB  - A safe BET: Apart from target engagement, subcellular location and tissue
      distribution are critical parameters in drug discovery. A novel, generalizable
      approach has been reported that involves exploiting click chemistry to elucidate
      these parameters. By using clickable analogues of known Bromodomain and
      extraterminal domain (BET) inhibitors, various labels were introduced in situ and
      utilized to determine the biological fate of these probes.

PMID- 29068505
TI  - Ruthenium(0)-Catalyzed Cycloaddition of 1,2-Diols, Ketols, or Diones via Alcohol
      Mediated Hydrogen Transfer.
AB  - Merging the characteristics of transfer hydrogenation and carbonyl addition, a
      broad new class of ruthenium(0)-catalyzed cycloadditions has been developed. As
      discussed in this Minireview, fused or bridged bicyclic ring systems are
      accessible in a redox-independent manner in C-C bond-forming hydrogen transfer
      reactions of diols, alpha-ketols, or 1,2-diones with diverse unsaturated
      reactants.

PMID- 29068508
TI  - Schlenk Lectureship: S. Harder / Kabiller Prize: R. S. Langer / Kabiller Young
      Investigator Award: L. Zhang / Wilhelm Manchot Research Professorship: P. S.
      Baran.

PMID- 29068509
TI  - Benzothiadiazole Versus Thiophene: Influence of the Auxiliary Acceptor on the
      Photovoltaic Properties of Donor-Acceptor-Based Copolymers.
AB  - Two donor-acceptor (D-A) type conjugated copolymers, P1 and P2, are designed and
      synthesized. A classical benzothiadiazole acceptor is used to replace a thiophene
      unit in the polymer chain of P1 to obtain P2 terpolymer. Compared with P1, P2
      exhibits broader absorption spectra, higher absorption coefficient, deeper lowest
      unoccupied molecular orbital level, and a relatively lower band gap. As a result,
      the P2-based solar cell exhibits a high power conversion efficiency (PCE) of
      6.60%, with a short-circuit current (J sc ) of 12.43 mA cm-2 , and a fill factor
      (FF) of 73.1%, which are higher than those of the P1-based device with a PCE of
      4.70%, a J sc of 9.43 mA cm-2 , and an FF of 61.6%.

PMID- 29068507
TI  - The maternal-zygotic transition and zygotic activation of the Mnemiopsis leidyi
      genome occurs within the first three cleavage cycles.
AB  - The maternal-zygotic transition (MZT) describes the developmental reprogramming
      of gene expression marked by the degradation of maternally supplied gene products
      and activation of the zygotic genome. While the timing and duration of the MZT
      vary among taxa, little is known about early-stage transcriptional dynamics in
      the non-bilaterian phylum Ctenophora. We sought to better understand the extent
      of maternal mRNA loading and subsequent differential transcript abundance during
      the earliest stages of development by performing comprehensive RNA-sequencing
      based analyses of mRNA abundance in single- and eight-cell stage embryos in the
      lobate ctenophore Mnemiopsis leidyi. We found 1,908 contigs with significant
      differential abundance between single- and eight-cell stages, of which 1,208
      contigs were more abundant at the single-cell stage and 700 contigs were more
      abundant at the eight-cell stage. Of the differentially abundant contigs, 267
      were exclusively present in the eight-cell samples, providing strong evidence
      that both the MZT and zygotic genome activation (ZGA) have commenced by the eight
      cell stage. Many highly abundant transcripts encode genes involved in molecular
      mechanisms critical to the MZT, such as maternal transcript degradation,
      serine/threonine kinase activity, and chromatin remodeling. Our results suggest
      that chromosomal restructuring, which is critical to ZGA and the initiation of
      transcriptional regulation necessary for normal development, begins by the third
      cleavage within 1.5 hr post-fertilization in M. leidyi.

PMID- 29068510
TI  - Characteristics of adrenal incidentalomas in a New Zealand centre.
AB  - BACKGROUND: Management of adrenal incidentalomas (AI) is becoming more
      conservative, based on international data showing a low incidence of functional
      or malignant lesions. The clinical characteristics of AI in New Zealand are
      unknown. Therefore, whether the AI guidelines apply to the New Zealand population
      is also unknown. AIMS: To investigate the clinical characteristics of patients
      with AI presenting to a tertiary-care centre in New Zealand. METHOD: This study
      prospectively evaluated consecutive patients aged 18 or older with AI, 1 cm or
      larger, diagnosed in Canterbury, New Zealand. A standardised nurse-led dedicated
      AI clinic was used, including clinical assessment, hormonal evaluation and
      imaging. RESULTS: From January 2010 to April 2016, 306 patients were referred to
      the AI clinic, 228 met the inclusion criteria. Most of those excluded were not
      true AI, due to imaging performed for known or suspected non-adrenal malignancy.
      The most common reason for imaging was abdominal pain (46%). Most cases were
      benign (96.5%) and 88.6% of all cases were non-functional. Of the functioning
      tumours (26 patients), 18 had subclinical Cushing syndrome, four had late-onset
      congenital adrenal hyperplasia, two had phaeochromocytoma and one had primary
      hyperaldosteronism. Three patients had primary adrenal cancer, one of whom was
      secreting excess cortisol. One adrenal metastasis was diagnosed. CONCLUSION: This
      study found a similar prevalence of functional and malignant AI as international
      centres, although mild cortisol excess and primary aldosteronism may be under
      represented. Therefore, the conservative approach to management of AI recommended
      in current guidelines is likely to be applicable to New Zealand population.

PMID- 29068511
TI  - Multiple hypotheses explain variation in extra-pair paternity at different levels
      in a single bird family.
AB  - Extra-pair paternity (EPP), where offspring are sired by a male other than the
      social male, varies enormously both within and among species. Trying to explain
      this variation has proved difficult because the majority of the interspecific
      variation is phylogenetically based. Ideally, variation in EPP should be
      investigated in closely related species, but clades with sufficient variation are
      rare. We present a comprehensive multifactorial test to explain variation in EPP
      among individuals in 20 populations of nine species over 89 years from a single
      bird family (Maluridae). Females had higher EPP in the presence of more helpers,
      more neighbours or if paired incestuously. Furthermore, higher EPP occurred in
      years with many incestuous pairs, populations with many helpers and species with
      high male density or in which males provide less care. Altogether, these
      variables accounted for 48% of the total and 89% of the interspecific and
      interpopulation variation in EPP. These findings indicate why consistent patterns
      in EPP have been so challenging to detect and suggest that a single predictor is
      unlikely to account for the enormous variation in EPP across levels of analysis.
      Nevertheless, it also shows that existing hypotheses can explain the variation in
      EPP well and that the density of males in particular is a good predictor to
      explain variation in EPP among species when a large part of the confounding
      effect of phylogeny is excluded.

PMID- 29068512
TI  - Chiral Discrimination through 1 H NMR and Luminescence Spectroscopy: Dynamic
      Processes and Solid Strip for Chiral Recognition.
AB  - The appropriate choice of the host molecules with well-defined optical activity
      (S-H/R-H) helps in the differentiation between two secondary ammonium ion
      derivative guest molecules with different optical activities (R-G/S-G) based on
      the fluorescence resonance energy transfer (FRET)-based luminescence responses.
      Crown ether-based host molecules with opposite chiral configurations (R-H, S-H)
      have been derived from 1,1'-bi-2-naphthol (BINOL) derivatives that have axially
      chiral biaryl centers. These chiral crown ethers form host-guest complexes (i.e.,
      [2]pseudorotaxanes) with chiral secondary ammonium ion derivatives (R-G, S-G).
      NMR spectroscopic studies show that the complexes are in a dynamic equilibrium in
      solution. Results of the 1 H NMR and fluorescence spectroscopic studies indicate
      a head-on orientation of the host and guest in the [2]pseudorotaxanes. The
      difference in the efficiency in the FRET-based responses between anthracene and
      the BINOL derivatives allow efficient chiral discrimination of the guests.
      Isothermal titration calorimetry and NMR investigations reveal that inclusion
      complexes between hosts and guests of the same chirality (R-H?R-G, S-H?S-G) are
      more stable relative to those of opposite chirality (R-H?S-G, S-H?R-G). However,
      FRET-based energy-transfer efficiency is higher for R-H?S-G and S-H?R-G
      complexes. NMR spectroscopic studies show that the relative orientation of the
      guest in the host cavity is significantly different when the host binds a guest
      of the same or opposite chirality; furthermore, the latter is more favorable for
      FRET, thus enabling discrimination between enantiomers. Interestingly, chiral
      discrimination of guest ions could also be achieved by using silica surfaces
      modified with chiral host molecules.

PMID- 29068515
TI  - Rapid preparation of methyltrimethoxy-modified magnetic mesoporous silica as an
      effective solid-phase extraction adsorbent.
AB  - A time-saving method was applied to synthesize methyltrimethoxy-modified magnetic
      mesoporous silica with or without p-toluenesulfonic acid as the catalyst for
      magnetic solid-phase extraction. The synthesized materials were systematically
      characterized. Results demonstrated that methyltrimethoxy modified magnetic
      mesoporous silica with p-toluenesulfonic acid as the catalyst has a relatively
      smaller aperture and extreme hydrophobicity (water contact angle of 135 degrees
      ). To evaluate the feasibility of these prepared materials as effective
      adsorbents, it was combined with gas chromatography and electron capture
      detection to determine 26 polychlorinated biphenyls in environmental water. The
      result revealed that methyltrimethoxy modified magnetic mesoporous silica with p
      toluenesulfonic acid as the catalyst had the best extraction efficiency and
      recovery. Under the optimized extracted conditions, the proposed method showed
      good linearity within the concentration range of 5 to 200 ng/L with correlation
      coefficients of 0.9969 to 0.9999. The limits of detection and quantification
      based on signal-to-noise ratios of 3 and 10 were in the range of 0.16 to 0.91 and
      0.52 to 3.0 ng/L, respectively. The polychlorinated biphenyl concentrations in
      environmental water samples were successfully determined using the developed
      method. PCB008 and PCB110 were 4.05 and 8.52 ng/L in Red-Star lake water (Hubei
      Province, China), respectively.

PMID- 29068513
TI  - ortho-Quinones and Analogues Thereof: Highly Reactive Intermediates for Fast and
      Selective Biofunctionalization.
AB  - Fast, selective and facile functionalization of biologically relevant molecules
      is a pursuit of ever-growing importance. A promising approach in this regard
      employs the high reactivity of quinone and quinone analogues for fast conjugation
      chemistry by nucleophilic addition or cycloadditions. Combined with in situ
      generation of these compounds, selective conjugation on proteins and surfaces can
      be uniquely induced in a time and spatially resolved manner: generation of a
      quinone can often be achieved by simple addition of an enzyme or stoichiometric
      amounts of chemoselective oxidant, or by exposure to light. In this Minireview,
      we discuss the generation and subsequent functionalization of quinones,
      iminoquinones, and quinone methides. We also discuss practical applications
      regarding these conjugation strategies.

PMID- 29068514
TI  - High incidence of aseptic hip necrosis in Hodgkin lymphoma patients treated with
      escalated BEACOPP receiving methylprednisolone.
AB  - BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen
      for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral
      head was previously reported to increase in patients treated with eBEACOPP, but
      so far, no systematic analysis of its frequency has been published. AIMS: To
      analyse the frequency and identify possible risk factors for AVN development in
      patients treated with eBEACOPP. METHODS: We identified 26 patients treated with
      eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive
      at the time of study. All patients were invited to participate in a cross
      sectional study; 17 patients responded and were evaluated by magnetic resonance
      imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed
      with AVN after receiving eBEACOPP treatment. AVN was not correlated with age,
      gender, number of received eBEACOPP cycles, irradiation therapy or cumulative
      dose of steroids administered. There were significantly more cases of AVN in
      patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The
      use of methylprednisolone was shown to be a risk factor for the development of
      AVN in patients treated with eBEACOPP and should not be the corticosteroid of
      choice in the treatment of patients with HL.

PMID- 29068516
TI  - Simultaneous determination of furfural and its degradation products, furoic acid
      and maleic acid, in transformer oil by the reversed-phase vortex-assisted liquid
      liquid microextraction followed by high-performance liquid chromatography.
AB  - To explore why the use of furfural as a transformer oil-paper insulation aging
      characteristic is problematic in real world application, we developed a method
      for the simultaneous determination of furfural, furoic acid, and maleic acid in
      transformer oil by reversed-phase vortex-assisted liquid-liquid microextraction
      combined with high-performance liquid chromatography. The conditions for the
      proposed method were optimized, and the obtained extract can be directly analyzed
      by high-performance liquid chromatography. The detection limits (signal-to-noise
      ratio = 3) of the method ranged from 1.0 to 4.6 MUg/L, the enrichment factors for
      furfural, furoic acid, maleic acid, and fumaric acid were 4.6, 25.1, 15.6, and
      17.5, respectively, and the recovery rates for three analytes (fumaric acid was
      undetected) range from 82.1 to 106.2%. The contents of furfural, furoic acid, and
      maleic acid resulted from accelerated aging of transformer insulation oil-paper
      were measured using the present method for the first time, and the aging samples
      were analyzed by liquid chromatography with mass spectrometry for the
      identification of furoic acid and maleic acid in the aging transformer oil
      samples. Using the optimal method, the target products of samples at different
      aging time were tracked and measured.

PMID- 29068519
TI  - Training.

PMID- 29068517
TI  - Hybrid BisQACs: Potent Biscationic Quaternary Ammonium Compounds Merging the
      Structures of Two Commercial Antiseptics.
AB  - Benzalkonium chloride (BAC) and cetyl pyridinium chloride (CPC) are two of the
      most common household antiseptics, but show weaker efficacy against Gram-negative
      bacteria as well as against methicillin-resistant Staphylococcus aureus (MRSA)
      strains, relative to other S. aureus strains. We prepared 28 novel quaternary
      ammonium compounds (QACs) that represent a hybrid of these two structures, using
      1- to 2-step synthetic sequences. The biscationic (bisQAC) species prepared show
      uniformly potent activity against six bacterial strains tested, with nine novel
      antiseptics displaying single-digit micromolar activity across the board. Effects
      of unequal chain lengths of two installed side chains had less impact than the
      overall number of side chain carbon atoms present, which was optimal at 22-25
      carbons. This is further indication that simple refinements to multiQAC
      architectures can show improvement over current household antiseptics.

PMID- 29068520
TI  - Lymphangiosarcoma of the hip arising in a congenital non-irradiated lymphangioma.

PMID- 29068518
TI  - Qualitative analysis of multiple compounds in raw and prepared Semen Cassiae
      coupled with multiple statistical strategies.
AB  - In China, Semen Cassiae is used clinically to improve eyesight, relieve
      constipation, and to treat headache and dizziness. Prepared Semen Cassiae is
      obtained by stir-frying raw Semen Cassiae until it turned dark brown, micro
      dilatancy, and overflow aroma. After processing, the therapeutic effects change
      the purgation effect is alleviated and the hepatoprotective effect is enhanced.
      To explore the changes in chemical compositions of Semen Cassiae after processing
      and clarify the material basis of the changed therapeutic effects, an ultra-high
      performance liquid chromatography with quadrupole time-of-flight mass
      spectrometry coupled with automated data analysis software and statistical
      strategy was developed. As a result, 53 compounds in raw Semen Cassiae and 43
      compounds in prepared Semen Cassiae were found, a total of 55 chemical compounds
      were identified. Principle component analysis and t-test were processed by
      Markerview 1.2.1 software. Finally, 39 peaks were found to be the main
      contributors to the significant difference (p < 0.05) between raw and prepared
      Semen Cassiae. Compared with raw Semen Cassiae, 19 peaks showed a higher
      intensity in prepared Semen Cassiae, while the contents of 20 compounds in
      prepared Semen Cassiae were lower, most of which belonged to naphthopyrones
      glycosides and anthraquinone glycosides.

PMID- 29068521
TI  - CERCLA-linked environmental impact and benefit analysis: Evaluating remedial
      alternatives for the Portland Harbor Superfund Site, Portland, Oregon, USA.
AB  - This analysis focused on evaluating the environmental consequences of
      remediation, providing indicators for the environmental quality pillar of 3
      "pillars" of the Portland Harbor Sustainability Project (PHSP) framework (the
      other 2 pillars are economic viability and social equity). The project an
      environmental impact and benefit analysis (EIBA) and an EIBA-based cost-benefit
      analysis. Metrics developed in the EIBA were used to quantify and compare
      remedial alternatives' environmental benefits and impacts in the human and
      ecological domains, as a result of remedial actions (relative to no action). The
      cost-benefit results were used to evaluate whether remediation costs were
      proportionate or disproportionate to the environmental benefits. Alternatives B
      and D had the highest overall benefit scores, and Alternative F was
      disproportionately costly relative to its achieved benefits when compared to the
      other remedial alternatives. Indeed, the costlier alternatives with larger
      remedial footprints had lower overall EIBA benefit scores-because of
      substantially more air emissions, noise, and light impacts, and more disturbance
      to business, recreational access, and habitat during construction-compared to the
      less costly and smaller alternatives. Put another way, the adverse effects during
      construction tended to outweigh the long-term benefits, and the net environmental
      impacts of the larger remedial alternatives far outweighed their small
      incremental improvements in risk reduction. Results of this Comprehensive
      Environmental Response Compensation and Liability Act (CERCLA)-linked
      environmental analysis were integrated with indicators of economic and social
      impacts of remediation in a stakeholder values-based sustainability framework.
      These tools (EIBA, EIBA-based cost-benefit analysis, economic impact assessment,
      and the stakeholder values-based integration) provide transparent and
      quantitative evaluations of the benefits and impacts associated with remedial
      alternatives, and should be applied to complex remediation projects to aid
      environmental decision making. Integr Environ Assess Manag 2018;14:22-31. (c)
      2017 The Authors. Integrated Environmental Assessment and Management published by
      Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology &
      Chemistry (SETAC).

PMID- 29068522
TI  - Influence of exercise on the structure of the anterior chamber of the eye.
AB  - PURPOSE: To measure changes in anterior chamber structure before and after
      exercise in healthy individuals using anterior segment optical coherence
      tomography (ASOCT). METHODS: Thirty-two healthy young individuals performed
      jogging for 20 min. Eye blinking rate was recorded during rest and exercise. The
      anterior chamber angle (ACA), angle opening distance at 500 MUm from the scleral
      spur (AOD500), trabecular-iris space area at 500 MUm from the scleral spur
      (TISA500), iris concavity (IC), iris concavity ratio (CR), iris thickness at 750
      MUm from the scleral spur (IT750), anterior chamber depth (ACD), anterior chamber
      width (ACW), pupil diameter (PD), intraocular pressure (IOP), blood pressure (BP)
      and heart rate (HR) were recorded before and after exercise. Anterior chamber
      angle (ACA), AOD500, TISA500, IC, IT750, ACD, ACW and PD were measured with
      ASOCT. RESULTS: Compared with rest, the blinking rate during exercise did not
      change significantly (13.04 +/- 5.80 versus 13.52 +/- 5.87 blinks/min, p =
      0.645). The average IOP (15.4 +/- 2.4 versus 12.4 +/- 2.1 mmHg), ACA (35.96 +/-
      11.35 versus 40.25 +/- 12.64 degrees), AOD500 (0.800 +/- 0.348 versus 0.942 +/-
      0.387 mm), TISA500 (0.308 +/- 0.155 versus 0.374 +/- 0.193 mm2 ), IC (-0.078 +/-
      0.148 versus -0.153 +/- 0.159 mm) and CR (-0.027 +/- 0.050 versus -0.054 +/-
      0.056) changed significantly (all p < 0.001), while the average IT750 (0.463 +/-
      0.084 versus 0.465 +/- 0.086 mm; p = 0.492), ACD (3.171 +/- 0.229 versus 3.175 +/
      0.238 mm; p = 0.543) and ACW (11.768 +/- 0.377 versus 11.755 +/- 0.378 mm; p =
      0.122) showed no significant change after exercise. CONCLUSION: The blinking rate
      did not change significantly during exercise, while ACA, AOD500 and TISA500
      increased after exercise. Exercise also induced or increased IC. These changes in
      anterior chamber structure were only associated with exercise, but not with the
      postexercise change in PD or IOP.

PMID- 29068523
TI  - A carbonothioate-based highly selective fluorescent probe with a large Stokes
      shift for detection of Hg2.
AB  - Mercury (Hg) is one of the heavy metal pollutants in the environment. Even a very
      small amount of mercury can cause serious harm to human beings. Herein, we
      reported a new carbonothioate-based fluorescent probe for the detection of Hg2+
      without interference from other metal ions. This probe possessed a very large
      Stokes shift (192 nm), which could improve the detection sensitivity by
      minimizing the interferences resulted from self-absorption or auto-fluorescence.
      With the addition of Hg2+ to the probe solution, considerable fluorescence
      enhancement was observed. Additionally, the Hg2+ concentration of 0-16 MUM and
      fluorescence intensity showed a good linear relationship (y = 22106* + 53108, R2 
      = 0.9955). Finally, the proposed probe was used to detect Hg2+ in real water
      samples, and its result was satisfactory. Therefore, our proposed probe would
      provide a promising method for the determination of Hg2+ in the environment.

PMID- 29068525
TI  - Success of ophthalmic pharmaceutical start-up companies.

PMID- 29068524
TI  - Effects of intravitreal aflibercept and ranibizumab on retinal vessel diameter
      measured using fluorescein angiography.

PMID- 29068526
TI  - Vacuum sealing with a 'flipper' for the treatment of plantar excision defects.

PMID- 29068527
TI  - A cationic beta-cyclodextrin as a dynamic coating for the separation of proteins
      in capillary electrophoresis.
AB  - A cationic cyclodextrin was used as dynamic coating for the capillary
      electrophoresis of a model mixture of proteins (i.e., ubiquitin, alpha
      lactoglobulin, cytochrome-c, and myoglobin) as positively charged species in a
      fused silica capillary. An interesting feature of the coating is that by simple
      adjustment of the concentration of cyclodextrin added into the background
      electrolyte, a neutral or positively charged surface, which was beneficial in
      preventing protein adsorption at the inner capillary wall surface, was obtained.
      This is the first demonstration of a dynamic coating that yielded a neutral
      surface for protein separations in capillary electrophoresis. Based on electro
      osmotic flow measurements, addition of 0.05 to 0.10 mg/mL quaternary beta
      cyclodextrin in a low pH electrolyte resulted in a neutral or positive surface
      (undetectable to very slow anodic electro-osmotic flow). The coating approach
      afforded the electrophoretic separation of the mixture of proteins at positive
      polarity with good repeatability and separation performance.

PMID- 29068528
TI  - Is oral moxifloxacin associated with bilateral acute iris transillumination?

PMID- 29068529
TI  - Dealing with the spiralling price of medicines: issues and solutions.
AB  - Escalating cost of medicines is rapidly becoming a serious threat to patients and
      health systems. This trend has been documented to impact patient outcomes
      adversely. As clinicians and tax payers, it is our responsibility to be aware of
      the potential detrimental effects spiralling costs have on our patients, our
      community and our health system and to mitigate these effects by exposing this
      issue to our respective professional societies, representatives of the
      pharmaceutical companies that we interact with, government regulatory bodies and
      to patients who we are caring for. Only through understanding and constructive
      actions will we be able to provide the best quality of care to our patients and
      continue to enjoy universal healthcare in our country.

PMID- 29068530
TI  - Postoperative aqueous humour flare as a surrogate marker for proliferative
      vitreoretinopathy development.
AB  - PURPOSE: As some surgical procedures have been shown to increase postoperative
      flare values and thus contribute to blood-ocular barrier breakdown, retinal
      reattachment surgery might influence the risk of developing proliferative
      vitreoretinopathy (PVR). Therefore, we investigated whether postoperative aqueous
      flare values are a surrogate marker for the development of postoperative PVR.
      METHODS: We prospectively included 195 patients with primary rhegmatogenous
      retinal detachment (RRD) and measured aqueous laser flare preoperatively, and at
      2 and 6 weeks postoperatively. Postoperative PVR was defined as reoperation for
      redetachment due to PVR membranes, within 6 months of initial surgery. Logistic
      regression and receiver operating characteristic (ROC) analysis determined
      whether higher postoperative flare values were associated with an increased risk
      of developing PVR later on. RESULTS: Reoperation for postoperative PVR was needed
      in 12 (6.2%) patients; in 18 (9.2%), reoperation was not related to PVR. The
      median flare value for patients who would develop PVR was significantly higher
      than that of patients who would not develop PVR, both at 2 weeks (p = 0.001) and
      6 weeks (p < 0.001) postoperatively. Logistic regression analyses showed that a
      higher flare value significantly increased the odds of developing PVR, either at
      2 weeks [odds ratio (OR) 1.027; 95% CI: 1.010-1.044] or 6 weeks (OR 1.076; 95%
      CI: 1.038-1.115). CONCLUSION: Flare values both at 2 and 6 weeks postoperatively
      seem a good surrogate marker in terms of sensitivity and specificity for the
      development of postoperative PVR but have only a modest positive predictive
      value. The 2-week value would be more useful in terms of early recognition of
      high-risk patients and hence give the possibility to better study effects of
      treatment methods.

PMID- 29068531
TI  - Intrinsically Disordered Proteome of Human Membrane-Less Organelles.
AB  - It is recognized now that various proteinaceous membrane-less organelles (PMLOs)
      are commonly found in cytoplasm, nucleus, and mitochondria of various eukaryotic
      cells (as well as in the chloroplasts of plant cells). Being different from the
      "traditional" membrane-encapsulated organelles, such as chloroplasts, endoplasmic
      reticulum, Golgi apparatus, lysosomes, mitochondria, nucleus, and vacuoles, PMLOs
      solve the cellular need to facilitate and regulate molecular interactions via
      reversible and controllable isolation of target molecules in specialized
      compartments. PMLOs possess liquid-like behavior and are believed to be formed as
      a result of biological liquid-liquid phase transitions (LLPTs, also known as
      liquid-liquid phase separation), where an intricate interplay between RNA and
      intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered
      domains and intrinsically disordered protein regions (IDPRs) may play an
      important role. This review analyzes the prevalence of intrinsic disorder in
      proteins associated with various PMLOs found in human cells and considers some of
      the functional roles of IDPs/IDPRs in biogenesis of these organelles.

PMID- 29068532
TI  - Alteration of Liver Peroxisomal and Mitochondrial Functionality in the NZO Mouse
      Model of Metabolic Syndrome.
AB  - PURPOSE: Metabolic syndrome (MetS) consists of five risk factors: elevated blood
      pressure and fasting glucose, visceral obesity, dyslipidemia, and
      hypercholesterinemia. The physiological impact of lipid metabolism indicated as
      visceral obesity and hepatic lipid accumulation on MetS is still under debate.
      One major cause of disturbed lipid metabolism might be dysfunction of cellular
      organelles controlling energy homeostasis, i.e., mitochondria and peroxisomes.
      EXPERIMENTAL DESIGN: The New Zealand Obese (NZO) mouse model exhibits a polygenic
      syndrome of obesity, insulin resistance, triglyceridemia, and
      hypercholesterolemia that resembles human metabolic syndrome. We applied a multi
      omics approach combining lipidomics with liver transcriptomics and top-down MS
      based organelle proteomics (2D-DIGE) of highly enriched mitochondria and
      peroxisomes in male mice, to investigate molecular mechanisms related to the
      impact of lipid metabolism in the pathophysiology of the metabolic syndrome.
      CONCLUSIONS AND CLINICAL RELEVANCE: Proteome analyses of liver organelles
      indicate differences in fatty acid and cholesterol metabolism, mainly influenced
      by PG-C1alpha/PPARalpha and other nuclear receptor mediated pathways. These
      results are in accordance with altered serum lipid profiles and elevated
      organelle functionality. These data emphasize that metabolic syndrome is
      accompanied with increased mitochondria and peroxisomal activity to cope with
      dyslipidemia and hypercholesterinemia driven hepatic lipid overflow in developing
      a fatty liver.

PMID- 29068533
TI  - Vertical Growth of 2D Amorphous FePO4 Nanosheet on Ni Foam: Outer and Inner
      Structural Design for Superior Water Splitting.
AB  - Rational design of highly efficient bifunctional electrocatalysts based on 3D
      transition-metal-based materials for oxygen evolution reaction (OER) and hydrogen
      evolution reaction (HER) is of great importance for sustainable energy conversion
      processes. Herein, a novel strategy involving outer and inner structural
      engineering is developed for superior water splitting via in situ vertical growth
      of 2D amorphous FePO4 nanosheets on Ni foam (Am FePO4 /NF). Careful experiments
      and density functional theory calculations show that the inner and outer
      structural engineering contributing to the synergistic effects of 2D morphology,
      amorphous structure, conductive substrate, and Ni-Fe mixed phosphate lead to
      superior electrocatalytic activity toward OER and HER. Furthermore, a two
      electrode electrolyzer assembled using Am FePO4 /NF as an electrocatalyst at both
      electrodes gives current densities of 10 and 100 mA cm-2 at potentials of 1.54
      and 1.72 V, respectively, which is comparable to the best bifunctional
      electrocatalyst reported in the literature. The strategies, introduced in the
      present work, may open new opportunities for the rational design of other 3D
      transition-metal-based electrocatalyst through an outer and inner structural
      control to strengthen the electrocatalytic performance.

PMID- 29068534
TI  - Freezing does not alter multiscale tendon mechanics and damage mechanisms in
      tension.
AB  - It is common in biomechanics to use previously frozen tissues, where it is
      assumed that the freeze-thaw process does not cause consequential mechanical or
      structural changes. We have recently quantified multiscale tendon mechanics and
      damage mechanisms using previously frozen tissue, where damage was defined as an
      irreversible change in the microstructure that alters the macroscopic mechanical
      parameters. Because freezing has been shown to alter tendon microstructures, the
      objective of this study was to determine if freezing alters tendon multiscale
      mechanics and damage mechanisms. Multiscale testing using a protocol that was
      designed to evaluate tendon damage (tensile stress-relaxation followed by
      unloaded recovery) was performed on fresh and previously frozen rat tail tendon
      fascicles. At both the fascicle and fibril levels, there was no difference
      between the fresh and frozen groups for any of the parameters, suggesting that
      there is no effect of freezing on tendon mechanics. After unloading, the
      microscale fibril strain fully recovered, and interfibrillar sliding only
      partially recovered, suggesting that the tendon damage is localized to the
      interfibrillar structures and that mechanisms of damage are the same in both
      fresh and previously frozen tendons.

PMID- 29068535
TI  - Tailored Modification of Thioacrylates in a Versatile, Sequence-Defined
      Procedure.
AB  - A strategy for the synthesis of sequence-defined oligomers using a selective side
      group insertion approach making use of thiophenol-catalyzed amidation reactions
      is herein reported. In this context, a new thiolactone-based, multistep,
      iterative protocol is designed, utilizing thioacrylates in combination with solid
      phase synthesis for step-by-step growth, resulting in sequence-defined oligomers.
      Sequence definition and structure variation are introduced by substituting the
      thioacrylate side groups with a wide variety of amines. The step-by-step growth
      of the oligomers is followed by liquid chromatography-mass spectrometry and high
      resolution mass spectroscopy to determine both conversion and purity.

PMID- 29068536
TI  - Outline of a sociology of decisionism.
AB  - I propose an agenda for empirical research on decision, choice, decision-makers,
      and decision-making qua social facts. Given society S, group G, or field F, I
      make a twofold sociological proposal. First, empirically investigate the
      conditions under which something-call it X-is taken to be a decision or choice,
      or the outcome of a decision-making process. What must X be like? What doesn't
      count (besides, presumably, myotatic reflexes and blushing)? Whom or what must X
      be done by? What can't be a decision-maker (besides, presumably, rocks and
      apples)? Second, empirically investigate how decision/choice concepts are used in
      everyday life, politics, business, education, law, technology, and science. What
      are they used for? To what extent do people understand and represent themselves
      and others as decision-makers? Where do decision-centric or "decisionist"
      understandings succeed? These aren't armchair, theoretical, philosophical
      questions, but empirical ones. Decision/choice concepts' apparent ubiquity in
      contemporary societies calls for a well-thought-out research program on their
      social life and uses.

PMID- 29068537
TI  - Anti-fibrotic function of Cu-bearing stainless steel for reducing recurrence of
      urethral stricture after stent implantation.
AB  - Recurrent stenosis is the main reason inducing the failure of urethral stricture
      treatment. Our previous study has found that the 316L type Cu bearing stainless
      steel (316L-Cu SS) showed antimicrobial activity and anti-encrustation
      performance when it was used for relieving urethral obstructer. However, whether
      it can reduce the occurrence of fibrosis or not, we need further investigation to
      compare the cellular and molecular responses of human urethral scar fibroblast
      cells (USFCs) on 316L-Cu SS and medical grade 316L stainless (316L SS, as a
      control). [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-
      sulfophenyl)- 2H-tetrazolium (MTS) and Transwell were used to assess the cellular
      responses, which confirmed that 316L-Cu SS could inhibit proliferation and
      migration of USFCs. Molecular expressions of fibrosis were evaluated by western
      blot, real-time quantitative polymerase chain reaction (qPCR), and Cu/Zn
      superoxide dismutase (CuZnSOD) measurement. The results indicated that up
      regulating of CuZnSOD attenuated the transforming growth factor-beta1 expression
      and phosphorylation of Smad3 after exposure to 316L-Cu SS. Besides, the content
      of collagen type I (COL1) and collagen type III (COL3) secreting into the culture
      medium measured by enzyme-linked immunosorbent assay were in accord with the
      results of messenger ribonucleic acids. Both of them exhibited lower levels of
      COL1/COL3 exposure to 316L-Cu SS, demonstrating the inhibitory performance of
      316L-Cu SS against fibrosis. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater, 106B: 2019-2028, 2018.

PMID- 29068538
TI  - Novel 1,3,5-triazine derivatives exert potent anti-cervical cancer effects by
      modulating Bax, Bcl2 and Caspases expression.
AB  - This study aimed to develop novel 1,3,5-triazine derivatives as potent anti
      cervical cancer agents. The compounds were synthesized in short steps with an
      excellent yield and characterized via various spectroscopic and analytical
      methods. A structure-activity relationship study suggested that electron
      withdrawing substituents showed greater anticancer activity than electron
      donating groups. Compound 7p (p-fluoro) showed the highest activity against
      cervical cancer cells. In a nude mouse xenograft model inoculated with HeLa
      cells, 7p showed dose-dependent inhibition of cervical tumour growth.
      Histopathological examination of excised tumour-bearing tissues showed that 7p
      improved the microstructure in a dose-dependent manner. Compound 7p also
      increased the proportions of HeLa cells in G0/G1 and S-phase and significantly
      decreased that of G2/M-phase. The effects of 7p on C-caspase-3, C-caspase-9, Bcl
      2 and Bax expression in HeLa cells were also determined.

PMID- 29068540
TI  - The molecular cross talk of the dystrophin-glycoprotein complex.
AB  - The proper function of skeletal muscles relies on their ability to process
      signals derived from motor neurons, transmit stimuli along the muscle fibers,
      contract, and regenerate efficiently after injury. The dystrophin-glycoprotein
      complex (DGC; also called the dystrophin-associated protein complex) plays a
      central role in all of these processes. It acts as a transmembrane platform that
      anchors the extracellular matrix (ECM) to the intracellular cytoskeleton and
      makes muscle fibers more resistant to injury. The DGC also contributes to the
      transmission of contraction-evoked force from the sarcomere to the ECM. The
      dysfunction of DGC-associated proteins can lead to myopathies, including
      Duchenne's muscular dystrophy, manifested by progressive muscle damage and
      impairments in regeneration. The DGC also plays a pivotal role in the
      organization of neuromuscular junctions (NMJs), where it stabilizes postsynaptic
      machinery, including receptors for the neurotransmitter acetylcholine (AChRs).
      Here, we focus on the role of the DGC complex in NMJ and skeletal muscle
      physiology and discuss the novel components that are associated with the complex.

PMID- 29068541
TI  - Reproducibility and acceptability of ultrasound measurements of head-perineum
      distance.
AB  - INTRODUCTION: We aimed to test the reproducibility of head-perineum distance
      (HPD) measurements using two different ultrasound devices and five examiners, to
      compare ultrasound measurements and clinical assessments and to study if
      ultrasound examinations were acceptable for women in labor. MATERIAL AND METHODS:
      A reproducibility study was performed at Lund University Hospital, Sweden and
      Landspitali University Hospital, Iceland from February 2015 to February 2017. The
      study population comprised 40 healthy women in labor. HPD was measured with three
      replicate measurements from each woman with two different ultrasound devices, and
      the measurements were compared with clinical assessments. Acceptability was
      tested with a visual analog scale (VAS), and the mean VAS score from both
      ultrasound devices was compared with the VAS score from clinical palpation.
      RESULTS: The median time interval between start of examinations with devices was
      10 min (range 1-26 min). The intra-observer repeatability coefficient was 4.3 mm
      and the intraclass correlation coefficient was 0.97 (95% CI 0.95-0.98). The
      intraclass correlation coefficient between the two devices was 0.86 (95% CI 0.74
      0.93) and limits of agreement were -9.6 mm to 16.6 mm. However, we observed a
      significant mean HPD difference between devices (3.5 mm; 95% CI 1.4-5.6 mm).
      Clinical assessments and the mean measurements of HPD were correlated (r = 0.64,
      p < 0.01). We found significant differences in acceptability in favor of
      ultrasound. The mean VAS score for both ultrasound devices was 2.0 vs. 4.1 for
      clinical examination (p < 0.01). CONCLUSION: We found excellent intra-observer
      repeatability, good correlation but significant difference between devices. Women
      reported less discomfort with ultrasound than with clinical examinations.

PMID- 29068539
TI  - Eosinophil persistence in vivo and sustained viability ex vivo in response to
      respiratory challenge with fungal allergens.
AB  - BACKGROUND: Eosinophils are immunomodulatory leucocytes that contribute to the
      pathogenesis of Th2-driven asthma and allergic lung diseases. OBJECTIVE: Our goal
      was to identify unique properties of eosinophils recruited to the lungs and
      airways of mice in response to challenge with asthma-associated fungal allergens.
      METHODS: Mice were challenged intranasally on days 0, 3 and 6 with a filtrate of
      Alternaria alternata. Recruited eosinophils were enumerated in bronchoalveolar
      lavage fluid. Eosinophils were also isolated from lungs of mice sensitized and
      challenged with Aspergillus fumigatus and evaluated ex vivo in tissue culture.
      RESULTS: Eosinophils persist in the airways for several weeks in response to
      brief provocation with A. alternata in wild-type, Gm-csf- and eotaxin-1-gene
      deleted mice, while eosinophils are recruited but do not persist in the absence
      of IL-13. Eosinophils isolated from the lungs A. alternata-challenged mice are
      cytokine-enriched compared to those from IL5tg mice, including 800-fold higher
      levels of eotaxin-1. Furthermore, eosinophils from the lungs and spleen of fungal
      allergen-challenged wild-type mice are capable of prolonged survival ex vivo, in
      contrast to eosinophils from both untreated and fungal allergen-challenged IL5tg
      mice, which undergo rapid demise in the absence of exogenous cytokine support.
      TNF-alpha (but not IL5, IL-3, eotaxin-1 or GM-CSF) was detected in supernatants
      of ex vivo eosinophil cultures from the lungs of fungal allergen-challenged wild
      type mice. However, neither TNF-alpha gene deletion nor anti-TNF-alpha
      neutralizing antibodies had any impact sustained eosinophil survival ex vivo.
      CONCLUSION AND CLINICAL RELEVANCE: Eosinophils are phenotypically and
      functionally heterogeneous. As shown here, eosinophils from fungal allergen
      challenged wild-type mice maintain a distinct cytokine profile, and, unlike
      eosinophils isolated from IL5tg mice, they survive ex vivo in the absence of
      exogenous pro-survival cytokine support. As treatments for asthma currently in
      development focus on limiting eosinophil viability via strategic cytokine
      blockade, the molecular mechanisms underlying differential survival merit further
      investigation.

PMID- 29068542
TI  - In Situ Coupling Strategy for the Preparation of FeCo Alloys and Co4 N Hybrid for
      Highly Efficient Oxygen Evolution.
AB  - An in situ coupling approach is developed to create a new highly efficient and
      durable cobalt-based electrocatalyst for the oxygen evolution reaction (OER).
      Using a novel cyclotetramerization, a task-specific bimetallic phthalocyanine
      based nanoporous organic framework is successfully built as a precursor for the
      carbonization synthesis of a nonprecious OER electrocatalyst. The resultant
      material exhibits an excellent OER activity with a low overpotential of 280 mV at
      a current density of 10 mA cm-2 and high durability in an alkaline medium. This
      impressive result ranks among the best from known Co-based OER catalysts under
      the same conditions. The simultaneous installation of multiple diverse cobalt
      based active sites, including FeCo alloys and Co4 N nanoparticles, plays a
      critical role in achieving this promising OER performance. This innovative
      approach not only enables high-performance OER activity to be achieved but
      simultaneously provides a means to control the surface features, thereby tuning
      the catalytic property of the material.

PMID- 29068543
TI  - Covalent Incorporation of Heparin Improves Chondrogenesis in Photocurable Gelatin
      Methacryloyl Hydrogels.
AB  - Multicomponent gelatin-methacryloyl (GelMA) hydrogels are regularly adopted for
      cartilage tissue engineering (TE) applications, where optimizing chemical
      modifications for preserving biofunctionality is often overlooked. This study
      investigates the biological effect of two different modification methods,
      methacrylation and thiolation, to copolymerize GelMA and heparin. The native
      bioactivity of methacrylated heparin (HepMA) and thiolated heparin (HepSH) is
      evaluated via thromboplastin time and heparan sulfate-deficient myeloid cell-line
      proliferation assay, demonstrating that thiolation is superior for preserving
      anticoagulation and growth factor signaling capacity. Furthermore, incorporating
      either HepMA or HepSH in chondrocyte-laden GelMA hydrogels, cultured for 5 weeks
      under chondrogenic conditions, promotes cell viability and chondrocyte phenotype.
      However, only GelMA-HepSH hydrogels yield significantly greater differentiation
      and matrix deposition in vitro compared to GelMA. This study demonstrates that
      thiol-ene chemistry offers a favorable strategy for incorporating bioactives into
      gelatin hydrogels as compared to methacrylation while furthermore highlighting
      GelMA-HepSH hydrogels as candidates for cartilage TE applications.

PMID- 29068544
TI  - Cisplatin-Rich Polyoxazoline-Poly(aspartic acid) Supramolecular Nanoparticles.
AB  - Cisplatin-rich supramolecular nanoparticles are constructed through the
      supramolecular inclusion interaction between the admantyl (Ad)-terminated
      poly(aspartic acid) (Ad-P(Asp)) and the beta-cyclodextrin (beta-CD)-terminated
      poly(2-methyl-2-oxazoline). In the formation of the nanoparticles, the beta
      CD/admantane inclusion complex integrates poly(2-methyl-2-oxazoline) and
      poly(aspartic acid) chains to form pseudoblock copolymers, followed by the
      coordination between carboxyl groups in P(Asp) block and cisplatin. This
      coordination interaction drives the formation of nanoparticle and enables
      cisplatin incorporated into the nanoparticles. The spherical cisplatin-rich
      supramolecular nanoparticles have 53% cisplatin-loading content, good stability,
      and effective inhibition of the cell proliferation when it is tested in H22
      cancer cells. Near-infrared fluorescence imaging of tumor bearing mice reveals
      that the cisplatin-rich nanoparticles can target the tumor in vivo effectively.

PMID- 29068545
TI  - Alkali-Mediated Miscibility of Gelatin/Polycaprolactone for Electrospinning
      Homogeneous Composite Nanofibers for Tissue Scaffolding.
AB  - Electrospun natural-synthetic composite nanofibers, which possess favorable
      biological and mechanical properties, have gained widespread attention in tissue
      engineering. However, the development of biomimetic nanofibers of hybrids remains
      a huge challenge due to phase separation of the polymer blends. Here, aqueous
      sodium hydroxide (NaOH) solution is proposed to modulate the miscibility of a
      representative natural-synthetic hybrid of gelatin (GT) and polycaprolactone
      (PCL) for electrospinning homogeneous composite nanofibers. Alkali-doped GT/PCL
      solutions and nanofibers examined at macroscopic, microscopic, and internal
      molecular levels demonstrate appropriate miscibility of GT and PCL after
      introducing the alkali dopant. Particularly, homogeneous GT/PCL nanofibers with
      smooth surface and uniform diameter are obtained when aqueous NaOH solution with
      a concentration of 10 m is used. The fibers become more hydrophilic and possess
      improved mechanical properties both in dry and wet conditions. Moreover,
      biocompatibility experiments show that stem cells adhere to and proliferate
      better on the alkali-modified nanofibers than the untreated one. This study
      provides a facile and effective approach to solve the phase separation issue of
      the synthetic-natural hybrid GT/PCL and establishes a correlation of
      compositionally and morphologically homogeneous composite nanofibers with respect
      to cell responses.

PMID- 29068546
TI  - Diatom-Inspired Silica Nanostructure Coatings with Controllable Microroughness
      Using an Engineered Mussel Protein Glue to Accelerate Bone Growth on Titanium
      Based Implants.
AB  - Silica nanoparticles (SiNPs) have been utilized to construct bioactive
      nanostructures comprising surface topographic features and bioactivity that
      enhances the activity of bone cells onto titanium-based implants. However, there
      have been no previous attempts to create microrough surfaces based on SiNP
      nanostructures even though microroughness is established as a characteristic that
      provides beneficial effects in improving the biomechanical interlocking of
      titanium implants. Herein, a protein-based SiNP coating is proposed as an
      osteopromotive surface functionalization approach to create microroughness on
      titanium implant surfaces. A bioengineered recombinant mussel adhesive protein
      fused with a silica-precipitating R5 peptide (R5-MAP) enables direct control of
      the microroughness of the surface through the multilayer assembly of SiNP
      nanostructures under mild conditions. The assembled SiNP nanostructure
      significantly enhances the in vitro osteogenic cellular behaviors of
      preosteoblasts in a roughness-dependent manner and promotes the in vivo bone
      tissue formation on a titanium implant within a calvarial defect site. Thus, the
      R5-MAP-based SiNP nanostructure assembly could be practically applied to
      accelerate bone-tissue growth to improve the stability and prolong the lifetime
      of medical implantable devices.

PMID- 29068547
TI  - Structural basis for the agonist action at free fatty acid receptor 1 (FFA1R or
      GPR40).
AB  - G-protein-coupled receptor 40 (GPR40) was recently identified as an interesting
      target for treatment of type 2 diabetes. The high level of expression in
      pancreatic beta cells and the dependence of glucose on stimulating the secretion
      of insulin led to great excitement in this field. The identification of this
      target was followed by the development of a series of agonists with great
      potential for the treatment of diabetes. All known agonists have the presence of
      a pharmacophoric carboxylic acid group in their structure, which makes several
      polar interactions at the binding site of this receptor. In this report, we
      provide a review of the structure-activity relationships of GPR40 agonists with a
      focus on the main strategies of medicinal chemistry used to develop each one of
      the main structural patterns exploited for this purpose. Additionally, we provide
      a general model for the design of GPR40 ligands that can help researchers to
      follow up some strategies and implement them in the development of novel agonists
      of this receptor.

PMID- 29068548
TI  - Granular Nanostructure: A Facile Biomimetic Strategy for the Design of Supertough
      Polymeric Materials with High Ductility and Strength.
AB  - The realization of high strength, large ductility, and great toughness for
      polymeric materials is a vital factor for practical applications in industry.
      Unfortunately, until now this remains a huge challenge due to the common opposing
      trends that exist when promoting improvements in these properties using materials
      design strategies. In the natural world, the cuticle of mussel byssus exhibits a
      breaking strain as high as 100%, which is revealed to arise from an architectural
      granular microphase-separated structure within the protein matrix. Herein, a
      facile biomimetic designed granular nanostructured polymer film is reported. Such
      biomimetic nanostructured polymer films show a world-record toughness of 122 (+/-
      6.1) J g-1 as compared with other polyvinyl alcohol films, with a breaking strain
      as high as 205% and a high tensile strength of 91.2 MPa, which is much superior
      to those of most engineering plastics. This portfolio of outstanding properties
      can be attributed to the unique nanoscale granular phase-separated structure of
      this material. These biomimetic designed polymer films are expected to find
      promising applications in tissue engineering and biomaterials fields, such as
      artificial skin and tendon, which opens up an innovative methodology for the
      design of robust polymer materials for a range of innovative future applications.

PMID- 29068550
TI  - 5-aminolevulinic acid exerts renoprotective effect via Nrf2 activation in murine
      rhabdomyolysis-induced acute kidney injury.
AB  - AIM: Acute kidney injury (AKI) is associated with chronic kidney disease (CKD),
      as well as high mortality, but effective treatments for AKI are still lacking. A
      recent study reported the prevention of renal injury, such as ischemia
      reperfusion injury (IRI), by 5-aminolevulinic acid (ALA), which induces an
      antioxidant effect. The current study aimed to investigate the effect of ALA in a
      rhabdomyolysis-induced mouse model of AKI created by intramuscular injection of
      50% glycerol. METHODS: Rhabdomyolysis-induced AKI was induced by an intramuscular
      injection of glycerol (5 ml/kg body weight) into mice. Administration of ALA (30
      mg/kg, by gavage) was started from 48 hours before or 24 hours after glycerol
      injection. The mice were sacrificed at 72 hours after glycerol injection. The
      roles of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1
      (HO-1), which is one of the Nrf2-related antioxidants, were further investigated
      through in vivo and in vitro methods. RESULTS: ALA markedly reduced renal
      dysfunction and tubular damage in mice with rhabdomyolysis-induced AKI. ALA
      administration decreased oxidative stress, macrophage infiltration, and
      inflammatory cytokines and apoptosis. The expression of Nrf2 was upregulated by
      ALA administration. However, administration of Zinc protoporphyrin-9 (ZnPPIX) to
      inhibit HO-1 activity did not abolish these improvements by ALA. The expression
      of Nrf2-associated antioxidant factors other than HO-1 was also increased.
      CONCLUSIONS: These findings indicate that ALA exerts its antioxidant activity via
      Nrf2-associated antioxidant factors to provide a renoprotective effect against
      rhabdomyolysis-induced AKI.

PMID- 29068551
TI  - Developments in the field of allergy in 2016 through the eyes of Clinical and
      Experimental Allergy.
AB  - In this article, we described the development in the field of allergy as
      described by Clinical and Experimental Allergy in 2016. Experimental models of
      allergic disease, basic mechanisms, clinical mechanisms, allergens, asthma and
      rhinitis, and clinical allergy are all covered.

PMID- 29068549
TI  - Expanding the genetic architecture and phenotypic spectrum in the skeletal
      ciliopathies.
AB  - Defects in the biosynthesis and/or function of primary cilia cause a spectrum of
      disorders collectively referred to as ciliopathies. A subset of these disorders
      is distinguished by profound abnormalities of the skeleton that include a long
      narrow chest with markedly short ribs, extremely short limbs, and polydactyly.
      These include the perinatal lethal short-rib polydactyly syndromes (SRPS) and the
      less severe asphyxiating thoracic dystrophy (ATD), Ellis-van Creveld (EVC)
      syndrome, and cranioectodermal dysplasia (CED) phenotypes. To identify new genes
      and define the spectrum of mutations in the skeletal ciliopathies, we analyzed
      152 unrelated families with SRPS, ATD, and EVC. Causal variants were discovered
      in 14 genes in 120 families, including one newly associated gene and two genes
      previously associated with other ciliopathies. These three genes encode
      components of three different ciliary complexes; FUZ, which encodes a planar cell
      polarity complex molecule; TRAF3IP1, which encodes an anterograde ciliary
      transport protein; and LBR, which encodes a nuclear membrane protein with sterol
      reductase activity. The results established the molecular basis of SRPS type IV,
      in which mutations were identified in four different ciliary genes. The data
      provide systematic insight regarding the genotypes associated with a large cohort
      of these genetically heterogeneous phenotypes and identified new ciliary
      components required for normal skeletal development.

PMID- 29068552
TI  - The Anopheles gambiae ATP-binding cassette transporter family: phylogenetic
      analysis and tissue localization provide clues on function and role in
      insecticide resistance.
AB  - The role of ATP-binding cassette (ABC) transporters in conferring insecticide
      resistance has received much attention recently. Here we identify ABC
      transporters differentially expressed in insecticide-resistant populations of the
      malaria vector, Anopheles gambiae. Although we found little evidence that the
      orthologues of the multidrug resistance proteins described in other species are
      associated with resistance in An. gambiae we did identify a subset of ABC
      proteins consistently differentially expressed in pyrethroid-resistant
      populations from across Africa. We present information on the phylogenetic
      relationship, primary sites of expression and potential role of ABC transporters
      in mediating the mosquito's response to insecticides. Furthermore we demonstrate
      that a paralogous group of eight ABCG transporters, clustered on chromosome 3R,
      are highly enriched in the legs of An. gambiae mosquitoes, consistent with a
      proposed role for this ABC subfamily in transport of lipids to the outer surface
      of the cuticle. Finally, antibodies raised against one of the most highly
      expressed ABC transporters in adult females, ABCG7 (AGAP009850), localized this
      transporter to the pericardial cells. These data will help prioritize members of
      this gene family for further localization and functional validation studies to
      identify the in vivo function of these transporters in the mosquito and determine
      whether elevated expression of members of this family contribute to insecticide
      resistance.

PMID- 29068554
TI  - Internal anal sphincter nerves - a macroanatomical and microscopic description of
      the extrinsic autonomic nerve supply of the internal anal sphincter.
AB  - AIM: The internal anal sphincter (IAS) contributes substantially to anorectal
      functions. While its autonomic nerve supply has been studied at the microscopic
      level, little information is available concerning the macroscopic topography of
      extrinsic nerve fibres. This study was designed to identify neural connections
      between the pelvic plexus and the IAS, provide a detailed topographical
      description, and give histological proof of autonomic nerve tissue. METHODS:
      Macroscopic dissection of pelvic autonomic nerves was performed under
      magnification in seven (five male, two female) hemipelvises obtained from body
      donors (67-92 years). Candidate structures were investigated by histological and
      immunohistochemical staining protocols to visualize nerve tissue. RESULTS: Nerve
      fibres could be traced from the anteroinferior edge of the pelvic plexus to the
      anorectal junction running along the neurovascular bundle anterolaterally to the
      rectum and posterolaterally to the prostate/vagina. Nerve fibres penetrated the
      longitudinal rectal muscle layer just above the fusion with the levator ani
      muscle (conjoint longitudinal muscle) and entered the intersphincteric space to
      reach the IAS. Histological and immunohistochemical findings confirmed the
      presence of nerve tissue. CONCLUSIONS: Autonomic nerve fibres supplying the IAS
      emerge from the pelvic plexus and are distinct to nerves entering the rectum via
      the lateral pedicles. Thus, they should be classified as IAS nerves. The
      identification and precise topographical location described provides a basis for
      nerve-sparing rectal resection procedures and helps to prevent postoperative
      functional anorectal disorders.

PMID- 29068553
TI  - Serum alpha1 -proteinase inhibitor concentrations in dogs with systemic
      inflammatory response syndrome or sepsis.
AB  - OBJECTIVE: To determine whether the concentration of serum canine alpha1 
      proteinase inhibitor (calpha1 -PI) has diagnostic or prognostic utility in dogs
      with sepsis or noninfectious systemic inflammatory response syndrome (SIRS).
      DESIGN: Prospective, observational study from May to December 2010. SETTING:
      University teaching hospital ICU. ANIMALS: Sixty-nine client-owned dogs: 19 dogs
      with SIRS or sepsis and 50 healthy control dogs. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Serum and plasma samples were collected from dogs
      with SIRS or sepsis on the day of hospital admission and once on the following 2
      days, and on a single day in healthy controls. Patients were assessed using the
      10-parameter Acute Patient Physiologic and Laboratory Evaluation (APPLEfull ) and
      5-parameter (APPLEfast ) score. Serum calpha1 -PI concentrations were measured,
      compared among groups of dogs, and evaluated for a correlation with the
      concentration of serum C-reactive protein, plasma interleukin-6, tumor necrosis
      factor-alpha, the APPLE scores, and survival to discharge. Serum calpha1 -PI
      concentrations were significantly lower in dogs with SIRS/sepsis (P < 0.001) than
      in healthy controls. While day 1 serum calpha1 -PI concentrations did not differ
      between dogs with SIRS and those with sepsis (P = 0.592), septic dogs had
      significantly lower serum calpha1 -PI concentrations on days 2 (P = 0.017) and 3
      (P = 0.036) than dogs with SIRS. Serum calpha1 -PI concentrations did not differ
      between survivors and nonsurvivors (P = 1.000), but were inversely correlated
      with the APPLEfull score (rho = -0.48; P = 0.040) and plasma interleukin-6
      concentrations (rho = -0.50; P = 0.037). CONCLUSIONS: These results suggest a
      role of calpha1 -PI as a negative acute phase protein in dogs. The concentration
      of serum calpha1 -PI at the time of hospital admission does not have utility to
      identify dogs with sepsis from those with noninfectious SIRS, but may be a useful
      surrogate marker for early stratification of illness severity.

PMID- 29068555
TI  - Diagnostic utility of cortactin antibodies in myasthenia gravis.
AB  - Patients with myasthenia gravis (MG) without antibodies to the acetylcholine
      receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as
      having double-seronegative myasthenia gravis (dSNMG). We used the sera from six
      dSNMG patients with positive immunohistochemistry assays in a protein array to
      screen reactivity with 9000 human proteins. We identified cortactin, an
      intracellular protein that interacts with agrin/MuSK favoring AChR aggregation,
      as a new antigen in dSNMG. We then designed an in-house enzyme-linked
      immunosorbent assay as a screening assay and confirmed these results by western
      blot. We found that 19.7% of dSNMG patients had anti-cortactin antibodies. In
      contrast, patients with AChR+ MG or other autoimmune disorders and healthy
      controls were positive at significantly lower rates. Five percent of healthy
      controls were positive. In a recent study, we screened sera from 250 patients
      (AChR+ MG, MuSK+ MG, dSNMG) and 29 healthy controls. Cortactin antibodies were
      identified in 23.7% of dSNMG and 9.5% AChR+ MG patients (P = 0.02). None of the
      MuSK+ MG patients, patients with other autoimmune disorders, or healthy controls
      had antibodies against cortactin. Patients with dSNMG cortactin+ MG were negative
      for anti-striated muscle and anti-LRP4 antibodies. Patients with dSNMG cortactin+
      MG presented ocular or mild generalized MG without bulbar symptoms. We conclude
      that cortactin autoantibodies are biomarkers of MG that, when present, suggest
      that the disease will be mild.

PMID- 29068557
TI  - In vitro study on the deterioration of polypropylene hernia repair meshes.
AB  - Despite the relative safety of the procedure, hernia repairs are often associated
      with chronic post-operative pain. Although this complication has been linked
      among others to mesh deterioration, details of the processes that lead this
      deterioration are still unknown. This work aims to bridge this gap by analyzing
      the chemical, physical and structural alterations in hernia repair meshes exposed
      to oxidative stress in vitro. Here, we developed a methodology to characterize
      effect of oxidation stress on structure and properties of polymeric hernia repair
      meshes. It was shown that structural changes in polypropylene meshes exposed to
      oxidative stress may involve formation of cross-links between the polymer chains,
      chain scissions, and hydrogen bonds between the carboxyl groups, which are formed
      in the material during the oxidation. These effects result in mesh stiffening,
      ultimately leading to chronic post-operative pain. Moreover, we demonstrated that
      Composix meshes are more vulnerable to the oxidative stress when compared with
      UltraPro meshes. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 2225-2234, 2018.

PMID- 29068556
TI  - A Review of Current Literature on Vital Sign Assessment of Physical Activity in
      Primary Care.
AB  - PURPOSE: To conduct an integrated review of the performance and implementation of
      two physical activity (PA) assessment tools, the exercise vital sign (EVS) and
      the physical activity vital sign (PAVS), in U.S. primary care practice. DESIGN:
      An integrative review following Whittemore and Knafl's methodology. METHODS:
      Medline and the Cumulative Index to Nursing and Allied Health Literature (CINAHL)
      databases were searched. Search terms were "exercise vital sign" OR "physical
      activity vital sign" AND "primary care". Additional inclusion criteria were
      studies conducted in the United States, published in English, in primary care,
      between 2010 and 2016. RESULTS: Nine studies met inclusion criteria. Five studies
      reported validity data of the EVS tool, while four studies reported data from the
      PAVS tool. Compared with the accelerometer, the EVS tool overestimated moderate
      vigorous PA, while the PAVS tool demonstrated moderate agreement in identifying
      those not meeting national PA guidelines. The EVS tool was successfully
      implemented in large, integrated practices utilizing electronic health record
      systems. PA documentation increased compared to non-EVS practices. The predictive
      ability of the PAVS tool for clinical outcomes was shown. Studies of PA
      assessment tool use in children were not found. CONCLUSIONS: Preliminary evidence
      on the validity of both the EVS and PAVS tools support cautious use of each as a
      screening tool in primary care. There were no data on reliability, with limited
      data on tool use in diverse populations or settings. Data in children, older
      adults, and diverse population subgroups were lacking. CLINICAL RELEVANCE: Two
      brief exercise vital signs tools have each shown some initial validity for use by
      primary care clinicians as measures to identify patients not meeting PA
      guidelines.

PMID- 29068559
TI  - Neuromuscular synapse electrophysiology in myasthenia gravis animal models.
AB  - The neuromuscular junction (NMJ) forms the synaptic connection between a motor
      neuron and a skeletal muscle fiber. In order to achieve a sustained muscle
      contraction, this synapse has to reliably transmit motor neuronal action
      potentials onto the muscle fiber. To guarantee successful transmission even
      during intense activation of the NMJ, a safety factor of neuromuscular
      transmission exists. In the neuromuscular disorder myasthenia gravis (MG),
      autoantibodies are directed against acetylcholine receptors or, in the rarer
      variants, against other postsynaptic NMJ proteins. This causes loss of functional
      acetylcholine receptors, which compromises the safety factor of neuromuscular
      transmission, leading to the typical fatigable muscle weakness of MG. With
      intracellular microelectrode measurement of (miniature) endplate potentials at
      NMJs in ex vivo nerve-muscle preparations from MG animal models, these functional
      synaptic defects have been determined in much detail. Here, we describe the
      electrophysiological events at the normal NMJ and the pathoelectrophysiology at
      NMJs of animal models for MG.

PMID- 29068558
TI  - Sodium-Containing Spinel Zinc Ferrite as a Catalyst Precursor for the Selective
      Synthesis of Liquid Hydrocarbon Fuels.
AB  - A microwave-assisted hydrothermal synthesis produces ZnFe2 O4 containing Na
      residue as a precursor to a CO2 hydrogenation catalyst that displays high CO2
      conversion and high selectivity to liquid hydrocarbon products in the gasoline
      and diesel range with high olefin-to-paraffin ratios. Compared to reference
      catalysts derived from Fe2 O3 and a ZnO-Fe2 O3 physical mixture, the ZnFe2 O4 
      derived catalyst contains well-dispersed iron particles with Zn serving as a
      structural promoter. A profound effect of the residual Na as an electronic
      promoter is also observed, which improves the selectivity for C5+ hydrocarbons
      and olefins. The ZnFe2 O4 -derived catalyst exhibits excellent performance in the
      CO2 Fischer-Tropsch reaction as it forms the active Hagg iron carbide (chi-Fe5 C2
      ) phase readily through the in situ carburization of iron.

PMID- 29068560
TI  - Extremely Vivid, Highly Transparent, and Ultrathin Quantum Dot Light-Emitting
      Diodes.
AB  - Displaying information on transparent screens offers new opportunities in next
      generation electronics, such as augmented reality devices, smart surgical
      glasses, and smart windows. Outstanding luminance and transparency are essential
      for such "see-through" displays to show vivid images over clear background view.
      Here transparent quantum dot light-emitting diodes (Tr-QLEDs) are reported with
      high brightness (bottom: ~43 000 cd m-2 , top: ~30 000 cd m-2 , total: ~73 000 cd
      m-2 at 9 V), excellent transmittance (90% at 550 nm, 84% over visible range), and
      an ultrathin form factor (~2.7 um thickness). These superb characteristics are
      accomplished by novel electron transport layers (ETLs) and engineered quantum
      dots (QDs). The ETLs, ZnO nanoparticle assemblies with ultrathin alumina
      overlayers, dramatically enhance durability of active layers, and balance
      electron/hole injection into QDs, which prevents nonradiative recombination
      processes. In addition, the QD structure is further optimized to fully exploit
      the device architecture. The ultrathin nature of Tr-QLEDs allows their conformal
      integration on various shaped objects. Finally, the high resolution patterning of
      red, green, and blue Tr-QLEDs (513 pixels in.-1 ) shows the potential of the full
      color transparent display.

PMID- 29068563
TI  - Workforce data and uncertainty: Uneasy but unavoidable partners.

PMID- 29068561
TI  - The effect of fasting on gastrointestinal motility in healthy dogs as assessed by
      sonography.
AB  - OBJECTIVE: To evaluate the effect of fasting on gastrointestinal (GI) motility in
      healthy dogs, as detected by 2D ultrasound. DESIGN: Prospective observational
      study. SETTING: University Distributed Veterinary Learning Community. ANIMALS:
      Ten healthy client-owned dogs. INTERVENTIONS: Dogs were fasted 24 hours following
      regular feeding. After this first feeding and during the 24 hour fasting period,
      2D ultrasound was performed to detect sonographically visible GI contractions of
      the stomach, duodenum, and jejunum/ileum at T = 30 minutes, 6 hours, 12 hours,
      and 24 hours. Dogs were then fed a second meal after the 24-hour fast and
      ultrasound was repeated 30 minutes later (T = 24.5 h). Each site was scanned
      twice at each time point. Each scan lasted 3 minutes. The results were averaged
      and then divided by 3 to determine contractions per minute. One-way repeated
      measures ANOVA with post hoc Tukey's comparison test was used to detect
      statistical differences over time for each site examined. MEASUREMENTS AND MAIN
      RESULTS: The mean GI contraction rates in the stomach, duodenum, and
      jejunum/ileum at T12 and T24 were significantly lower than the GI contraction
      rates at T30, T3, T6, and T24.5 (P < 0.05). The mean GI contraction rates in the
      stomach, duodenum, and jejunum/ileum at T30, T3, T6, and T24.5 were not
      statistically different from each other. CONCLUSIONS: Results of this study show
      that 2D sonography can be used to evaluate GI motility in dogs and that GI
      contraction rate decreases significantly in the stomach, duodenum, and
      jejunum/ileum after 12-24 hours of fasting.

PMID- 29068562
TI  - Do geographic differences or socioeconomic disparities affect survival in
      sinonasal squamous cell carcinoma?
AB  - BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignancy in the
      sinonasal tract. We present the first population-based analysis that examines
      geographic differences in demographic and clinical characteristics, socioeconomic
      factors, treatment modality, and disease-specific survival (DSS) of this entity.
      METHODS: All cases of sinonasal squamous cell carcinoma (SNSCC) were queried
      using the U.S. Surveillance, Epidemiology, and End Results (SEER) registry from
      1973 to 2013. Patients were stratified by geographic location and characteristics
      such as demographics (age, gender, race, metropolitan/nonmetropolitan status, and
      income), stage at diagnosis, and treatment modality. Survival data were generated
      using Kaplan-Meier regression analysis. RESULTS: In total, 6094 patients were
      identified; 15.3% were from the East, 16.3% from the Midwest, 19.3% from the
      South, and 49.1% from the West. Patients from the South were younger (p < 0.001).
      The South had the highest proportion of patients who were black (p < 0.001),
      lived in nonmetropolitan areas (p < 0.001), and presented with localized disease
      (p < 0.001). Southern patients also had the lowest median income (p < 0.05), and
      were least likely to be treated with both surgery and radiotherapy (p < 0.001).
      The South exhibited the lowest 20-year DSS compared to all other regions (p <
      0.001). CONCLUSION: SNSCC patients from the South had the poorest long-term DSS,
      despite being most likely to present with localized disease. The South had the
      highest proportion of patients who were black, resided in rural or urban towns,
      had the lowest median income, and did not receive standard combination therapy,
      compared to the East, Midwest, and West.

PMID- 29068564
TI  - The American Society of Pediatric Hematology/Oncology workforce assessment: Part
      1-Current state of the workforce.
AB  - The American Society of Pediatric Hematology/Oncology (ASPHO) recognized recent
      changes in medical practice and the potential impact on pediatric hematology
      oncology (PHO) workforce. ASPHO surveyed society members and PHO Division
      Directors between 2010 and 2016 and studied PHO workforce data collected by the
      American Board of Pediatrics and the American Medical Association to characterize
      the current state of the PHO workforce. The analysis of this information has led
      to a comprehensive description of PHO physicians, professional activities, and
      workplace. It is important to continue to collect data to identify changes in
      composition and needs of the PHO workforce.

PMID- 29068566
TI  - Scaffold-Based microRNA Therapies in Regenerative Medicine and Cancer.
AB  - microRNA-based therapies are an advantageous strategy with applications in both
      regenerative medicine (RM) and cancer treatments. microRNAs (miRNAs) are an
      evolutionary conserved class of small RNA molecules that modulate up to one third
      of the human nonprotein coding genome. Thus, synthetic miRNA activators and
      inhibitors hold immense potential to finely balance gene expression and
      reestablish tissue health. Ongoing industry-sponsored clinical trials inspire a
      new miRNA therapeutics era, but progress largely relies on the development of
      safe and efficient delivery systems. The emerging application of biomaterial
      scaffolds for this purpose offers spatiotemporal control and circumvents
      biological and mechanical barriers that impede successful miRNA delivery. The
      nascent research in scaffold-mediated miRNA therapies translates know-how learnt
      from studies in antitumoral and genetic disorders as well as work on plasmid
      (p)DNA/siRNA delivery to expand the miRNA therapies arena. In this progress
      report, the state of the art methods of regulating miRNAs are reviewed. Relevant
      miRNA delivery vectors and scaffold systems applied to-date for RM and cancer
      treatment applications are discussed, as well as the challenges involved in their
      design. Overall, this progress report demonstrates the opportunity that exists
      for the application of miRNA-activated scaffolds in the future of RM and cancer
      treatments.

PMID- 29068565
TI  - The American Society of Pediatric Hematology/Oncology workforce assessment: Part
      2-Implications for fellowship training.
AB  - The American Society of Pediatric Hematology/Oncology (ASPHO) solicited
      information from division directors and fellowship training program directors to
      capture pediatric hematology/oncology (PHO) specific workforce data of 6 years
      (2010-2015), in response to an increase in graduating fellows during that time.
      Observations included a stable number of physicians and advanced practice
      providers (APPs) in clinical PHO, an increased proportion of APPs hired compared
      to physicians, and an increase in training-level first career positions. Rapid
      changes in the models of PHO care have significant implications to current and
      future trainees and require continued analysis to understand the evolving
      discipline of PHO.

PMID- 29068567
TI  - Therapeutic administration of bone marrow-derived mesenchymal stromal cells
      reduces airway inflammation without up-regulating Tregs in experimental asthma.
AB  - BACKGROUND: Prophylactic administration of mesenchymal stromal cells (MSCs)
      derived from adipose (AD-MSC) and bone marrow tissue (BM-MSC) in ovalbumin
      induced asthma hinders inflammation in a Treg-dependent manner. It is uncertain
      whether MSCs act through Tregs when inflammation is already established in asthma
      induced by a clinically relevant allergen. OBJECTIVE: Evaluate the effect of
      therapeutic administration of MSCs on inflammation and Treg cells in house dust
      mite (HDM)-induced asthma. METHODS: BM-MSCs and AD-MSCs were administered
      intratracheally to C57BL/6 mice 1 day after the last HDM challenge. Lung
      function, remodelling and parenchymal inflammation were assayed 3 or 7 days after
      MSCs treatment, through invasive plethysmography and histology, respectively.
      Bronchoalveolar lavage fluid (BALF) and mediastinal lymph nodes (mLNs) were
      assessed regarding the inflammatory profile by flow cytometry, ELISA and qRT-PCR.
      MSCs were studied regarding their potential to induce Treg cells from primed and
      unprimed lymphocytes in vitro. RESULTS: BM-MSCs, but not AD-MSCs, reduced lung
      influx of eosinophils and B cells and increased IL-10 levels in HDM-challenged
      mice. Neither BM-MSCs nor AD-MSCs reduced lung parenchymal inflammation, airway
      hyperresponsiveness or mucus hypersecretion. BM-MSCs and AD-MSCs did not up
      regulate Treg cell counts within the airways and mLNs, but BM-MSCs decreased the
      pro-inflammatory profile of alveolar macrophages. Co-culture of BM-MSCs and AD
      MSCs with allergen-stimulated lymphocytes reduced Treg cell counts in a cell-to
      cell contact-independent manner, although co-culture of both MSCs with unprimed
      lymphocytes up-regulated Treg cell counts. CONCLUSIONS: MSCs therapeutically
      administered exert anti-inflammatory effects in the airway of HDM-challenged
      mice, but do not ameliorate lung function or remodelling. Although MSC pre
      treatment can increase Treg cell numbers, it is highly unlikely that the MSCs
      will induce Treg cell expansion when lymphocytes are allergenically primed in an
      established lung inflammation.

PMID- 29068568
TI  - Stimulation of a calcified cartilage connecting zone by GDF-5-augmented fibrin
      hydrogel in a novel layered ectopic in vivo model.
AB  - Tissue engineering approaches for reconstructing full-depth cartilage defects
      need to comprise a zone of calcified cartilage to tightly anchor cartilage
      constructs into the subchondral bone. Here, we investigated whether growth and
      differentiation factor-5-(GDF-5)-augmented fibrin hydrogel can induce a calcified
      cartilage-layer in vitro that seamlessly connects cartilage-relevant biomaterials
      with bone tissue. Human bone marrow stromal cells (BMSCs) were embedded in fibrin
      hydrogel and subjected to chondrogenesis with TGF-beta with or without GDF-5
      before constructs were implanted subcutaneously into SCID mice. A novel layered
      ectopic in vivo model was developed and GDF-5-augmented fibrin with BMSCs was
      used to glue hydrogel and collagen constructs onto bone disks to investigate
      formation of a calcified cartilage connecting zone. GDF-5 significantly enhanced
      ALP activity during in vitro chondrogenesis while ACAN and COL2A1 mRNA,
      proteoglycan-, collagen-type-II- and collagen-type-X-deposition remained similar
      to controls. Pellets pretreated with GDF-5 mineralized faster in vivo and formed
      more ectopic bone. In the novel layered ectopic model, GDF-5 strongly supported
      calcified cartilage formation that seamlessly connected with the bone. Pro
      chondrogenic and pro-hypertrophic activity makes GDF-5-augmented fibrin an
      attractive bioactive hydrogel with high potential to stimulate a calcified
      cartilage connecting zone in situ that might promote integration of cartilage
      scaffolds with bone. Thus, GDF-5-augmented fibrin hydrogel promises to overcome
      poor fixation of biomaterials in cartilage defects facilitating their long-term
      regeneration. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 2214-2224, 2018.

PMID- 29068569
TI  - Role of thiamine in Huntington's disease pathogenesis: In vitro studies.
AB  - BACKGROUND: Oxidative stress accompanies neurodegeneration and also causes
      abnormalities in thiaminedependent processes. These processes have been reported
      to be diminished in the brains of patients with several neurodegenerative
      diseases. OBJECTIVES: The aim of this work was to conduct a comparative analysis
      of the impact of supplemented thiamine on the viability of human B lymphocytes
      with CAG abnormal expanded huntingtin gene (mHTT) (GM13509) and control, B
      lymphocytes without mHTT (GM14467) through the following studies: determination
      of the supplemented thiamine concentrations, which are effective for cell growth
      stimulation after incubation in thiamine deficit conditions; determination of
      cell capability to intake the exogenous thiamine; evaluation of exogenous
      thiamine influence on the profile of the genes related to thiamine and energy
      metabolism; determination of ATP synthesis and activities of thiamine-dependent
      enzymes, KGDHC and BCKDHC in the intact cells and upon the exogenous thiamine.
      MATERIAL AND METHODS: The following methods were used: EZ4U test for cell growth
      analysis; HPLC for determination of thiamine intake and ATP synthesis, qRT-PCR
      for evaluation of the gene profiles and spectrophotometric method for KGDHC and
      BCKDHC activities determination. RESULTS: Maximal cell growth stimulation was
      observed at 2.5 mM in GM14467 up to 135% of the control culture and at 5.0 mM in
      GM13509 cells up to 165% of the control culture. Native levels of total ATP and
      KGDHC and BCKDHC activities in both cell types were comparable and did not
      changed upon thiamine deficit or supplementation. GM13509 cells showed more of an
      increase in growth stimulation upon thiamine supplementation than GM14467 cells
      and this effect was reflected in the increase of intracellular thiamine
      concentration. CONCLUSIONS: The above results and reported changes in expression
      of GAPDH, IDH1 and SLC19A3 genes observed upon thiamine deficit conditions
      suggest that intracellular thiamine status and energy metabolism can have a role
      in HD pathogenesis.

PMID- 29068570
TI  - The role of certain gene polymorphisms involved in the apoptotic pathways in
      polycythemia vera and essential thrombocytosis.
AB  - BACKGROUND: Polycythemia vera (PV) and essential thrombocytosis (ET) are
      hematological disorders characterized by excessive production of mature and
      functional blood cells. These cellular disorders are thought to be associated
      with impaired apoptosis, which is one of the major cellular death mechanisms in
      hematopoietic cells. OBJECTIVES: In this study, our objective was to examine the
      association between potential polymorphisms of the Bcl 2, Bax, Fas and Fas Ligand
      genes involved in apoptosis and the occurrence of PV and ET. MATERIAL AND
      METHODS: A total of 93 patients diagnosed with PV (n = 38) or ET (n = 55) at the
      Department of Hematology were included in this study, and 93 healthy individuals
      served as controls. DNA isolation was performed in blood samples obtained from
      both groups of subjects to determine the Bcl 2, Bax, Fas, and Fas L genotypes
      using the real-time PCR method. RESULTS: No statistically significant differences
      between controls and patients were found in terms of Fas -670 G > A (rs1800682),
      Fas -1377 G > A (rs2234767), Fas L IVS2 -124 A > G (rs5030772), Bax -248 G > A
      (rs4645878) and Bcl 2 -938 C > A (rs2279115) polymorphisms, genotypes, and allele
      frequency (p > 0.05). CONCLUSIONS: The results show that polymorphisms in the Bcl
      2, Bax, Fas, and Fas Ligand genes involved in the apoptotic pathways may not play
      a role in the pathogenesis of PV and ET.

PMID- 29068572
TI  - The assessment of prosthetic needs of ESRD patients and the general population in
      Poland on the basis of the Eichner classification and teeth number: A brief,
      preliminary report.
AB  - BACKGROUND: End-stage renal disease (ESRD) patients are considered as a group of
      high risk of oral cavity diseases. One of the determinants of alveolar bone loss
      and increased teeth mobility in ESRD patients might be the bone abnormalities
      associated with chronic kidney disease-mineral and bone disorder (CKD-MBD).
      OBJECTIVES: The aim of the study was to compare the general health condition,
      number and location of teeth in a group of ESRD patients with the group of peers
      from general population and revealing the risk factors of tooth loss. MATERIAL
      AND METHODS: The ESRD group included 63 patients, 23 females and 40 males,
      undergoing dialysis with a mean age of 62.4 +/- 15.6. The general population
      sample consisted of 37 people, 20 females and 17 males, applying for general
      practitioner visit, with a mean age of 65.5 +/- 11.1. All the participants were
      using just public health care insurance. The data analysis was based on
      anamnesis, history of CKD, selected biochemical parameters of blood tests and
      clinical examination. RESULTS: There was no statistical difference in the
      prosthetic needs of patients undergoing dialysis and the general population. In
      both groups the situation is alarming. CONCLUSIONS: The new procedures are needed
      to develop complex health care for ESRD and general population patients,
      emphasizing prophylaxis of tooth-loss and prosthetic treatment in order to
      maintain good level of life quality.

PMID- 29068571
TI  - Location of the ischemic focus in rehabilitated stroke patients with impairment
      of executive functions.
AB  - BACKGROUND: Executive dysfunctions are part of the clinical symptoms of a stroke
      and can inhibit the process of rehabilitation. Patients with impaired executive
      functions may manifest aggression, impulsiveness, impaired thinking and planning.
      OBJECTIVES: The aim of this study was to assess the effect of the ischemic focus
      location on the effectiveness of physiotherapy in improving the executive
      functions in patients after stroke. MATERIAL AND METHODS: Ninety patients after
      unilateral ischemic cerebral stroke were studied. We studied 45 patients treated
      at the Department of Rehabilitation and Physical Medicine of the WAM University
      Hospital of Lodz for 5 weeks. The rehabilitation program included: kinesitherapy,
      physiotherapy, speech therapy, psychological consultations and psychotherapy. The
      control group consisted of patients who were waiting for admission to the
      Department of Rehabilitation. The patients in both groups were divided into three
      subgroups with different locations of stroke: front, back and subcortical.
      Executive functions were measured by the Wisconsin Card Sorting Test (WCST), the
      trail making test (TMT - A, TMT - B), the verbal fluency test (VFT). RESULTS:
      Patients rehabilitated in the hospital with the front and subcortical lesion
      location reported improvement in executive functions in terms of a greater number
      of the analyzed indicators of the Wisconsin Card Sorting Test (WCST) than those
      with the back lesion location. Patients rehabilitated at home with the
      subcortical lesion location did not experience a significant improvement in
      executive functions in any of the analyzed indicators of the Wisconsin Card
      Sorting Test (WCST). Most of the indicators, with the exception of the total
      errors of Wisconsin Card Sorting Test (WCST) and TMT B, have not been modified by
      the location of stroke. CONCLUSIONS: Executive dysfunction occurs not only in
      patients with an anterior location of the stroke, but also in the posterior and
      subcortical locations. Patients with a subcortical location of the stroke require
      more treatment to mitigate the dysfunction.

PMID- 29068573
TI  - En bloc resection and prosthesis implantation to treat malignant fibrous
      histiocytoma of the humerus.
AB  - BACKGROUND: Malignant fibrous histiocytoma (MFH) of the bone is a rare tumor.
      Most studies comparing limb salvage and amputation have reported that limb
      salvage had no adverse effect on the long-term survival of patients. This study
      evaluates the oncological outcomes of limb salvage procedures that were used for
      15 patients with MFH of the humerus. OBJECTIVES: The aim of this study was to
      assess the functional and oncological outcomes of patients with malignant fibrous
      histiocytoma of the humerus after en bloc resection and prosthesis implantation.
      MATERIAL AND METHODS: A retrospective review of the charts of 15 patients who had
      undergone resection of malignant fibrous histiocytoma of the humerus followed by
      reconstruction with prosthesis was used in this study. A functional evaluation
      was based on Enneking's modified system of the functional evaluation of surgical
      management for musculoskeletal tumors. Complications of the procedures were also
      analyzed. RESULTS: Eight men and 7 women at an average age of 52.9 years were
      included in the study. The tumor involved the distal humerus in 3 patients, the
      proximal humerus in 8 patients and the mid-shaft humerus in 4 patients. Excellent
      results were achieved in 4 patients, good to fair in 10 and poor in 1. One
      patient had local recurrence. Pulmonary metastases occurred in 6 patients.
      CONCLUSIONS: Limb salvage surgery with chemotherapy is a viable treatment option
      for patients with malignant fibrous histiocytoma of the humerus.

PMID- 29068574
TI  - Total antioxidant capacity in Mediterranean beta-thalassemic patients.
AB  - BACKGROUND: Beta thalassemia major (BT) is an inherited blood disorder caused by
      reduced or absent synthesis of the hemoglobin beta chains, associated with
      profound anemia, jaundice, splenomegaly, expanded bone marrow volume, siderosis
      and cardiomegaly. Because of repeated blood transfusions, BT patients are
      subjected to peroxidative tissue injury due to secondary iron overload.
      OBJECTIVES: The aim of the study was to analyze: 1) the total antioxidant
      capacity (TAC) value in BT patients (study group) and their healthy controls
      (control group) from Greece (Central Macedonia) and Italy (Sardinia);
      correlations between 2) the TAC and ferritin levels of BT patients, and 3) the
      TAC and ferritin values in BT patients with different chelation therapies.
      MATERIAL AND METHODS: The studied group consisted of 60 subjects diagnosed with
      BT (41 female, mean age: 41.5 +/- 9.5 years) and 40 healthy controls matched with
      age and sex (31 female, mean age: 38.5 +/- 3.7 years). Desferrioxamine (DFO) was
      the basic previous chelation regimen for all BT patients. Antioxidant activity
      was assayed spectrophotometrically, using a TAC Kit (Total Antioxidant Capacity
      Colorimetric assay kit, produced by Cayman Chemical Co.), and ferritin was
      assayed by immunoturbidimetry. RESULTS: Lower levels of TAC were observed in BT
      patients of both countries when compared with controls (1.83 mmol/L vs 2.7 mmol/L
      in the Italian study group and controls and 2.42 mmol/L vs 3.2 mmol/L in the
      Greek study group and controls). There were no significant correlations between
      plasmatic TAC and ferritin. Furthermore, deferasirox was the only chelation
      treatment in which TAC showed a correlation in both regions. CONCLUSIONS: Our
      results potentially suggest that the reduced levels of TAC detectable in BT
      patients could demonstrate their reduced antioxidant defensive mechanisms.

PMID- 29068575
TI  - Evaluation of the anterior chamber angle in pseudoexfoliation syndrome.
AB  - BACKGROUND: Pseudoexfoliation syndrome (PEX) is the most frequently identifiable
      cause of secondary open-angle glaucoma, known as pseudoexfoliation glaucoma. The
      exact pathophysiology and etiology of PEX and associated glaucoma remains
      obscure. OBJECTIVES: The purpose of this study was to determine the differences
      in the morphology of the anterior chamber angle in people with pseudoexfoliation
      syndrome and pseudoexfoliation glaucoma compared to a control group. We also
      evaluated the correlation between intraocular pressure (IOP) and pigmentation of
      the angle with the amount of exfoliated material in the anterior segment.
      MATERIAL AND METHODS: The study group was composed of 155 eyes from 103 patients
      aged between 43 and 86 years. Each patient underwent a complete ophthalmological
      examination. RESULTS: Some difference was found in intraocular pressure between
      the PEX group and the control group and between the pseudoexfoliation glaucoma
      group and the control group, but no significant difference was found between the
      2 study groups. There was a significant difference in the incidence of some
      degree of pigmentation in the anterior chamber angle and no difference in the
      widths of the angle between each group. A significant positive relationship was
      observed between intraocular pressure and the degree of pigmentation of the
      anterior chamber angle in both the PEX group and the pseudoexfoliation glaucoma
      group. CONCLUSIONS: The results of this study indicate that the amount of
      pigmentation and exfoliation material in the anterior segment significantly
      correlates with the level of IOP and possibly with the degree of trabecular
      dysfunction. It seems that for clear identification of PEX and pseudoexfoliation
      glaucoma factors, clinical assessment appears to be insufficient.

PMID- 29068576
TI  - Assessment of the primary stability of root analog zirconia implants designed
      using cone beam computed tomography software by means of the Periotest(r) device:
      An ex vivo study. A preliminary report.
AB  - BACKGROUND: The implant primary stability is a fundamental prerequisite for a
      success of osseointegration process which determines the prosthetic
      reconstruction time. OBJECTIVES: The aim of the present study was to assess the
      quality and precision of modern conical bone computer tomography (CBCT) software
      in preparing root analog zirconia implants (RAZIs) by measuring its primary
      stability by means of the Periotest device. MATERIAL AND METHODS: Thirteen pig
      jaws with proper erupted first premolar (P1) teeth were used in the study. The
      CBCT examination was conducted in the area of the P1 tooth in each mandible. The
      3-dimensional (3D) view of each tooth was designed from CBCT scan. The created 3D
      images were used to prepare root analog zirconia implants milled from a medical
      grade zirconia block by means of laboratory milling. The RAZIs and titanium
      implants were placed into an alveolar socket after the tooth had been removed.
      The primary stability of the teeth before their extraction (G1), RAZIs (G2) and
      titanium implants (G3) were checked by Periotest devices. RESULTS: The mean
      results in PTV were: 15.9, 3.35, 12.7 for G1, G2 and G3 group, respectively.
      RAZIs during immediate loading achieved a significantly higher primary stability
      (lower Periotest value) as compared to the teeth and implants. CONCLUSIONS: The
      modern CBCT device allows us to design a precise image of an extracted tooth for
      the purpose of manufacturing a root analog implant. The additional feature of the
      surgical protocol using RAZI is the possibility of avoiding the augmentation
      procedure, which reduces the whole cost of the treatment.

PMID- 29068577
TI  - Which organ should be considered a reference in diffusion weighted imaging of the
      abdomen?: The reproducibility of ADC measurements of the spleen and the renal
      cortex on a 1.5T MR.
AB  - BACKGROUND: Diffusion weighted imaging (DWI) is a useful tool for the evaluation
      of focal lesions in the liver or kidneys, as well as for the diagnosis and
      assessment of the liver fibrosis process. Some reports show that the spleen and
      kidneys may serve as reference organs in the staging of liver fibrosis or the
      evaluation of focal liver lesions. OBJECTIVES: The aim of the study was to
      determine whether the spleen and renal cortex can be used as reference organs in
      the DWI technique. MATERIAL AND METHODS: The study group included 36 patients
      with no liver, spleen or renal pathologies and without any infections or
      hematologic disease. All the examinations were performed using a 1.5T MR unit
      with a conventional phased array body coil. Image interpretation and apparent
      diffusion coefficient (ADC) measurements were done by 3 experienced radiologists.
      RESULTS: There was a statistically significant difference between the ADC values
      noted by 2 of the examiners in the upper/middle and lower part of the spleen
      parenchyma. There were no statistically significant differences between the ADC
      values obtained by all 3 examiners in all the parts of each kidney. There were no
      statistically significant differences between the examiners' ADC values for the
      spleen and kidneys. The mean ADC values for the left kidney showed the highest
      measurement reproducibility. CONCLUSIONS: The study showed that the renal cortex
      seems to be an appropriate region for performing reference ADC measurements.
      Further studies on a larger group of patients and using various DWI protocols
      should be performed to ascertain the best conditions for maximizing the
      reproducibility of ADC measurements.

PMID- 29068578
TI  - The effect of desflurane and propofol protocols on preconditioning.
AB  - BACKGROUND: Preconditioning is one of the most powerful mechanisms preventing the
      myocardial ischemic damage that occurs during coronary artery bypass grafting.
      OBJECTIVES: We aimed to investigate the effects of different propofol and/or
      desflurane administration protocols in terms of the prevention of ischaemia
      reperfusion damage. MATERIAL AND METHODS: Ninety patients, aged > 18 years,
      American Society of Anesthesiologists (ASA) category III, scheduled to undergo
      primary elective coronary artery bypass grafting (CABG), were included in the
      study. During maintenance, the patients in group 1 (n = 30) received a propofol
      infusion (5-6 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h); the
      patients in group 2 (n = 30) also received a propofol infusion (5-6 mg/kg/h)
      combined with a fentanyl infusion (3-5 mcg/kg/h), but they were also given 6%
      desflurane inhalation for 15 min both before cross-clamping of the aorta and
      after removal of the clamp; the patients in group 3 (n = 30) received a propofol
      infusion (2-3 mg/kg/h) combined with a fentanyl infusion (3-5 mcg/kg/h) and
      received the continuous 6% desflurane inhalation. Blood samples were drawn in the
      preoperative period (S1), during cardiopulmonary bypass, before cross-clamping
      the aorta (S2), after removal of the cross-clamp (S3) and 24 h after the
      operation (S4). RESULTS: All groups were similar in terms of age and BMI (p >
      0.05). TNF-alpha levels were higher at S3 compared to S1, S2 and S4 (p > 0.001).
      The TNF-alpha levels at S4 were lower in group 3 than those in group 1 and group
      2 (p < 0.05). In all groups, h-FABP levels showed an increase in S3 but were
      significantly lower at S4 (p < 0.05). In group 3, h-FABP levels at S2 and S3 were
      significantly lower than those in group 1 (p < 0.05). There was a moderate
      correlation between h-FABP and TNF-alpha levels (Spearman's rho = 0.472, p <
      0.001). CONCLUSIONS: On the basis of the measurement of h-FABP and TNF-alpha, low
      dose propofol and continuous desflurane inhalation provide more effective
      preconditioning than propofol alone or a short course of desflurane in patients
      undergoing CABG.

PMID- 29068579
TI  - Usefulness of a new anthropometric indicator - VAI (Visceral Adiposity Index) in
      the evaluation of metabolic and hormonal disorders in women with polycystic ovary
      syndrome.
AB  - BACKGROUND: Visceral adiposity index (VAI) is a new anthropometric indicator that
      makes it possible to define the risk of obesity-related cardiometabolic
      complications even before the diagnosis of metabolic syndrome. OBJECTIVES:
      Evaluating the usefulness of VAI in order to differentiate metabolically
      unhealthy women (MU-PCOS) and defining the usefulness of this index in everyday
      practice. MATERIAL AND METHODS: A prospective study was conducted among 43 women
      who met the Rotterdam criteria for diagnosing polycystic ovarian syndrome. Body
      composition was measured using bioelectrical impedance analysis. Statistical
      analysis was performed using STATISTICA v. 10 and relevant statistical tests. The
      adopted significance level was p = 0.05. RESULTS: Based on the study results, a
      significant positive correlation was found between the value of VAI and the
      concentration of insulin (r = 0.33; p < 0.01), HOMA index (r = 0.46; p < 0.01)
      and FAI (r = 0.54; p < 0.01). It was also shown that there is a significant
      negative correlation between VAI and the concentration of SHBG (r = -0.53; p <
      0.01) and HDL cholesterol (r = -0.88; p < 0.01). In the group of metabolically
      unhealthy women, the research showed a significantly higher value of free
      testosterone, SHGB, DHEAS and FAI (p < 0.05). CONCLUSIONS: Visceral adiposity
      index makes it possible to introduce early prevention of metabolic disorders
      (including cardiometabolic disorders), as well as to evaluate the increase of
      hyperandrogenemia in women with polycystic ovary syndrome. The use of the cut-off
      point of VAI = 1.675 is a simple way to evaluate women with MU-PCOS.

PMID- 29068580
TI  - Orthodontic intrusion of periodontally-compromised maxillary incisors: 3
      dimensional finite element method analysis.
AB  - BACKGROUND: Loading of the compromised periodontium with orthodontic forces
      produces different results than those achieved in patients with healthy
      periodontal support. Determining the force value at a level preventing further
      deterioration of the patient's periodontal status, thus delivering the most
      precisely individualized "dose" of loading, seems to be crucial for the
      successful intrusion of teeth with reduced periodontal support. OBJECTIVES: The
      aim of the study was to determine the range of force values efficiently intruding
      maxillary incisors without further compromising the initially-impaired
      periodontal status. Finite element analysis (FEA), allowing estimation of the
      stress and strain distribution, was the method of choice. MATERIAL AND METHODS:
      The CT scans of a periodontally-compromised patient were segmented using
      InVesalius software. A model - based on NURBS surfaces - was adjusted to the CT
      scans in order to obtain both smooth and natural curvatures of each model
      segment. All relevant tissues were modeled as separate volumes. The geometric
      model was discretized in order to create a numerical model for applying Ansys
      software (v. 15.07) and using APDL. The central incisors were loaded with
      external intrusive forces, ranging from 0.1 to 0.4 N. RESULTS: The simulation,
      performed iteratively, showed that even the lowest force value - 0.1 N - causes
      stress changes in the alveolus and on the root surfaces, with a tendency of
      stress increasing towards the bottom of the alveolus and root apex. It is also
      notable that during the application of forces of equal magnitude, the
      stress/strain distribution was significantly higher around tooth 21, which
      displayed the highest range of PDL reduction. Application of the same force level
      created a higher stress-strain response around tooth 21, and the characteristics
      were less homogenous. CONCLUSIONS: A force value of 0.1 N applied in vivo might
      produce the most effective tooth intrusion and bone modeling which favors bone
      defect regeneration.

PMID- 29068582
TI  - Prevalence of cardiovascular disease risk factors among pharmacy students from
      Wroclaw Medical University (Poland).
AB  - BACKGROUND: Atherosclerotic processes begin in childhood and their development
      worsens during adolescence. Early prevention of CVD risk factors may have an
      important impact on the future health of young people. It can be also helpful in
      reducing the costs of treating CVD later in life. OBJECTIVES: The aim of this
      study was to assess the prevalence of selected cardiovascular disease risk
      factors among pharmacy students. MATERIAL AND METHODS: The study group consisted
      of 1,168 pharmacy students (892 women and 276 men) from Wroclaw Medical
      University. The average age was 22.9 years among women and 23.2 years among men.
      This cross-sectional study was conducted between 2004-2012. RESULTS: 27.5% of men
      and 7.1% of women were found to be overweight, while visceral obesity was found
      in 15.2% and in 10.1% of students, respectively. Hypertension was diagnosed in
      27.2% of men and in 7.8% of women. Low physical activity was declared by 41.9% of
      women and by 31.9% of men. There were 22.1% of men and 10% of women who were
      current smokers. The majority of the study group did not consume enough fruits
      and vegetables (women 61.8%, men 75%). Body mass index (BMI) was positively
      associated with waist and hip measurements, waist-to-hip ratio (WHR) and body fat
      percentage, while blood pressure was positively associated with BMI and waist
      circumference. It was found that men with high physical activity had lower BMIs,
      body fat percentage, waist and hip circumferences, WHR, diastolic blood pressure
      and heart rate than those who declared low physical activity. Comparing women
      with high physical activity to those with low physical activity, only lower heart
      rate was observed. CONCLUSIONS: A higher prevalence of cardiovascular risk
      factors was found more often among men than women. Preventive actions which
      promote proper nutrition, more physical activity, smoking cessation and regular
      blood pressure checks and lipid profile tests should be implemented for the
      students.

PMID- 29068581
TI  - Serum ICAM-1, VCAM-1 and E-selectin levels in patients with primary and secondary
      Sjogren's syndrome.
AB  - BACKGROUND: Typical features of Sjogren's syndrome (SS) are severe xerostomia and
      xerophthalmia which are basic diagnostic criteria. OBJECTIVES: The aim of this
      study was to compare the serum levels of soluble (s) intercellular adhesion
      molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sE-selectin
      between primary (pSS), secondary (sSS) and healthy subjects (HS). We correlated
      these results with selected clinical parameters of disease activity and
      parameters of the severity of xerostomia and xerophthalmia. MATERIAL AND METHODS:
      The serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by enzyme
      linked immunosorbent assay (ELISA) in 16 patients with pSS, 18 with sSS and 15
      HS. Eye dryness and xerostomia were assessed by the Schirmer's test, the Fox test
      and the visual analogue scale (VAS). RESULTS: The levels of sICAM-1 in pSS and
      sVCAM-1 in sSS patients were significantly higher when compared to HS (p = 0.02
      and p = 0.048, respectively). There were no differences between pSS and sSS. In
      pSS, sVCAM-1 correlated positively with VAS (rS = 0.52, p = 0.04) and the Fox
      test (rS = 0.66, p=0.01). In sSS, sE-selectin correlated positively with sICAM-1
      (rS = 0.54, p = 0.01), the duration of the disease (rS = 0.51, p = 0.03) and
      negatively with the Schirmer's test (rS = 0.59, p = 0.04). sICAM-1 correlated
      positively with the erythrocyte sedimentation rate (ESR) value (rS = 0.59, p =
      0.01). CONCLUSIONS: sVCAM-1 reflects xerostomia in pSS. sICAM-1 and sE-selectin
      may be additional parameters of sSS activity.

PMID- 29068583
TI  - The reliability of three psoriasis assessment tools: Psoriasis area and severity
      index, body surface area and physician global assessment.
AB  - BACKGROUND: A wide variety of psoriasis assessment tools have been proposed to
      evaluate the severity of psoriasis in clinical trials and daily practice. The
      most frequently used clinical instrument is the psoriasis area and severity index
      (PASI); however, none of the currently published severity scores used for
      psoriasis meets all the validation criteria required for an ideal score.
      OBJECTIVES: The aim of this study was to compare and assess the reliability of 3
      commonly used assessment instruments for psoriasis severity: the psoriasis area
      and severity index (PASI), body surface area (BSA) and physician global
      assessment (PGA). MATERIAL AND METHODS: On the scoring day, 10 trained
      dermatologists evaluated 9 adult patients with plaque-type psoriasis using the
      PASI, BSA and PGA. All the subjects were assessed twice by each physician.
      Correlations between the assessments were analyzed using the Pearson correlation
      coefficient. Intra-class correlation coefficient (ICC) was calculated to analyze
      intra-rater reliability, and the coefficient of variation (CV) was used to assess
      inter-rater variability. RESULTS: Significant correlations were observed among
      the 3 scales in both assessments. In all 3 scales the ICCs were > 0.75,
      indicating high intra-rater reliability. The highest ICC was for the BSA (0.96)
      and the lowest one for the PGA (0.87). The CV for the PGA and PASI were 29.3 and
      36.9, respectively, indicating moderate inter-rater variability. The CV for the
      BSA was 57.1, indicating high inter-rater variability. CONCLUSIONS: Comparing the
      PASI, PGA and BSA, it was shown that the PGA had the highest inter-rater
      reliability, whereas the BSA had the highest intra-rater reliability. The PASI
      showed intermediate values in terms of interand intra-rater reliability. None of
      the 3 assessment instruments showed a significant advantage over the other. A
      reliable assessment of psoriasis severity requires the use of several independent
      evaluations simultaneously.

PMID- 29068584
TI  - Hydronephrosis in the course of ureteropelvic junction obstruction: An
      underestimated problem? Current opinions on the pathogenesis, diagnosis and
      treatment.
AB  - Ureteropelvic junction obstruction (UPJO) causes a reduction in the urine flow
      from the renal pelvis into the ureter. Untreated UPJO may cause hydronephrosis,
      chronic infection or urolithiasis and will often result in progressive
      deterioration of renal function. Most cases of UPJO are congenital; however, the
      disease can be clinically silent until adulthood. Other causes, both intrinsic
      and extrinsic, are acquired and include urolithiasis, post
      operative/inflammatory/ischemic stricture, fibroepithelial polyps, adhesions and
      malignancy. In the past, the most frequent symptom of UPJO in neonates and
      infants was a palpable flank mass. Nowadays, thanks to the widespread use of
      maternal and prenatal ultrasound examinations, asymptomatic hydronephrosis is
      diagnosed very early. In adults and older children symptoms may include
      intermittent abdominal or flank pain, nausea, vomiting and hematuria. In addition
      to high specificity and sensitivity in detecting UPJO, modern technologically
      advanced equipment such as ultrasound, magnetic resonance imaging and computed
      tomography provides a lot of information about the function of the affected
      kidney and the anatomy of the surrounding tissues. Treatment options for UPJO
      include a wide spectrum of approaches, from active surveillance or minimally
      invasive endourologic techniques to open, laparoscopic or robotic pyeloplasty.
      The main goal of therapy is to relieve symptoms and maintain or improve renal
      function, but it is difficult to define treatment success after UPJO therapy.

PMID- 29068585
TI  - MicroRNA in cardiovascular biology and disease.
AB  - MicroRNAs (miRNAs) are members of a non-coding RNA family. They act as negative
      regulators of protein translation by affecting messenger RNA (mRNA) stability;
      they modulate numerous signaling pathways and cellular processes, and are
      involved in cell-to-cell communication. Thus, studies on miRNAs offer an
      opportunity to improve our understanding of complex biological mechanisms. In the
      cardiovascular system, miRNAs control functions of various cells, such as
      cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts. The
      pivotal role of miRNAs in the cardiovascular system provides a new perspective on
      the pathophysiology of disorders like myocardial infarction, hypertrophy,
      fibrosis, heart failure, arrhythmia, inflammation and atherosclerosis. MiRNAs are
      differentially expressed in diseased tissue and can be released into circulation.
      Manipulation of miRNA activity may influence the course of a disease. Therefore,
      miRNAs have become an active field of research for developing new diagnostic and
      therapeutic tools. This review discusses emerging functions of miRNAs in
      cardiogenesis, heart regeneration and the pathophysiology of cardiovascular
      diseases.

PMID- 29068586
TI  - Systemic sclerosis sine scleroderma.
AB  - Systemic sclerosis is a rare generalized disease with scleroderma, i.e. skin
      thickening as one of the most common symptoms. The disease has 2 main subsets,
      diffuse and limited forms. The subset known as systemic sclerosis sine
      scleroderma (ssSSc) is a very rare subset characterized by the total or partial
      absence of cutaneous manifestations of systemic sclerosis with the occurrence of
      internal organ involvement and serologic abnormalities. The classification of
      ssSSc into 3 groups was proposed. Type I (complete) is characterized by the lack
      of any cutaneous changes typical for the disease at least until systemic
      sclerosis-related insufficiency of any internal organ occurs. Type II
      (incomplete) is characterized by the absence of sclerodactyly, but other
      cutaneous involvements (e.g. calcifications, telangiectasies, pitting scars) can
      be found. Type III (delayed) is characterized by clinical internal organ
      involvement typical for systemic sclerosis that has appeared before skin changes
      (complete or incomplete). In general, the demographic and clinical
      characteristics of the ssSSc patients suggest that they are similar to those with
      diffuse or limited form of the disease. Diagnosis of ssSSc still remains
      difficult and this disease form should be considered in all cases of unexplained
      fibrotic involvement of the internal organs.

PMID- 29068587
TI  - The Notch signaling pathway in head and neck squamous cell carcinoma: A meta
      analysis.
AB  - BACKGROUND: The Notch signaling pathway has been associated with the regulation
      of self-renewal capacity, cell cycle exit, and survival. However, the
      relationship between the Notch signaling pathway and HNSCC remains controversial.
      OBJECTIVES: A meta-analysis was conducted to evaluate the role of Notch signaling
      pathway in HNSCC. MATERIAL AND METHODS: Relevant studies published until March
      31, 2015 were identified by searching the PubMed, EMBASE and Ovid database.
      RESULTS: A total of 9 articles were eligible for this meta-analysis. The meta
      analysis results showed that the expression of Notch1, Notch3 and NICD was
      significantly higher in HNSCC as compared with control tissue. There was no
      significant difference in Jagged1 and HES1 expression between HNSCC and control
      tissue. Stratified analysis results showed that the expression of Notch1 was
      significantly higher in poor differentiation, III and IV stage and positive lymph
      node metastasis patients. Additionally, over-expression of Notch1, NICD, HES1 and
      DLL4 significantly predicted poor OS in HNSCC patients. CONCLUSION: The Notch
      signaling pathway plays an important role in tumor development of HNSCC.
      Inhibition of the Notch signaling pathway is a potential therapeutic method of
      HNSCC.

PMID- 29068588
TI  - Potential protective effect of N-acetyl cysteine in acoustic trauma: An
      experimental study using scanning electron microscopy.
AB  - BACKGROUND: Oxidative stress has been associated with pathological processes
      involved in acoustic trauma. OBJECTIVES: In this prospective experimental study,
      we investigated the potential preventive effect of N-acetyl cysteine (NAC) in
      rats exposed to acoustic trauma (AT). Light microscopic and scanning electron
      microscopic (SEM) evaluations were performed. MATERIAL AND METHODS: Healthy
      Wistar albino rats (n = 18) were divided into 3 groups: group 1 (control group, n
      = 6), group 2 (acoustic trauma group, n = 6), and group 3 (AT+NAC group, n = 6).
      The rats in group 2 were exposed to AT. The rats in group 3 received NAC at a
      dose of 100 mg/kg/day by gavage for 7 days, and then 10 min after the 7th-day
      dose, they were exposed to AT. RESULTS: From light and scanning electron
      microscopy evaluations in the control group, the cochlear structure and
      epithelium were normal. In group 2 (AT group), extensive hair cell loss was
      observed in the cochlea by light microscopy evaluation. In the SEM evaluation,
      various epithelial damage and loss of stereocilia were also observed. In group 3
      (AT+NAC group), decreased damage with preserved cochlear structures was seen by
      light microscopy. In the SEM evaluation, although stereocilia loss was also seen,
      nearly normal cell structures and vertical and symmetrical alignment of
      stereocilia structures were observed compared to the AT group. CONCLUSIONS: NAC
      reduced cochlear damage due to acoustic trauma. Because NAC has antioxidant
      capacity, AT mat have caused an increase in free radicals and death of outer hair
      cells. NAC is an antioxidant agent and it prevented cochlear damage due to AT in
      rats.

PMID- 29068589
TI  - Chosen single nucleotide polymorphisms (SNPs) of enamel formation genes and
      dental caries in a population of Polish children.
AB  - BACKGROUND: It is increasingly emphasized that the influence of a host's factors
      in the etiology of dental caries are of most interest, particularly those
      concerned with genetic aspect. OBJECTIVES: The aim of the study was to analyze
      the genotype and allele frequencies of single nucleotide polymorphisms (SNPs) in
      AMELX, AMBN, TUFT1, TFIP11, MMP20 and KLK4 genes and to prove their association
      with dental caries occurrence in a population of Polish children. MATERIAL AND
      METHODS: The study was performed in 96 children (48 individuals with caries -
      "cases" and 48 free of this disease - "controls"), aged 20-42 months, chosen out
      of 262 individuals who had dental examination performed and attended 4 day
      nurseries located in Poznan (Poland). From both groups oral swab was collected
      for molecular evaluation. Eleven selected SNPs markers were genotyped by Sanger
      sequencing. Genotype and allele frequencies were calculated and a standard chi2
      analysis was used to test for deviation from Hardy-Weinberg equilibrium. The
      association of genetic variations with caries susceptibility or resistance was
      assessed by the Fisher's exact test and p <= 0.05 was considered statistically
      significant. RESULTS: Five markers were significantly associated with caries
      incidence in children in the study: rs17878486 in AMELX (p < 0.0001), rs34538475
      in AMBN (p < 0.0001), rs2337360 in TUFT1 (p < 0.0001), and rs2235091 (p = 0.0085)
      and rs198969 (p = 0.0069) in KLK4. Genotype and allele frequencies indicated both
      risk and protective variants for these markers. CONCLUSIONS: Single nucleotide
      polymorphisms in AMELX, AMBN, TUFT1, KLK4 genes may be considered as a risk
      factor for dental caries occurrence in Polish children.

PMID- 29068590
TI  - Vitamin E (alpha tocopherol) attenuates toxicity and oxidative stress induced by
      aflatoxin in rats.
AB  - BACKGROUND: Aflatoxins are toxic metabolites produced by Aspergillus flavus and
      Aspergillus parasiticus and are classified as group I carcinogens by the
      International Agency for Research on Cancer (IARC). OBJECTIVES: The purpose of
      this study was to investigate the possible preventive role of vitamin E (Vit E)
      on aflatoxin (AF) induced toxicity by using biochemical and histopathological
      approaches. MATERIAL AND METHODS: Wistar-Albino rats were divided into 4 groups
      as follows: control group, Vit E group (Vit E was administered), AFB1 group (a
      single dose of AFB1 was administered), AF + Vit E group (AF and Vit E were
      administered). The effects of Vit E on AFB1 induced tissue toxicity were
      evaluated by using malondialdehyde (MDA), reduced glutathione (GSH) levels,
      antioxidant enzyme activities, and histopathological examination in tissues.
      RESULTS: AF caused the oxidative stress by the increased MDA level and the
      reduced GSH level, glutathioneS-transferase (GST), catalase (CAT), glutathione
      peroxidase (GSH-Px), superoxide dismutase (SOD), and glucose-6-phosphate
      dehydrogenase (G6PD) activities in tissues. Plasma aspartate transaminase (AST),
      alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase
      (LDH) activities, creatinine, and urea concentrations significantly increased;
      whereas, chloride, phosphorus, and magnesium concentrations were insignificantly
      affected. Plasma glucose, protein and sodium concentrations significantly
      decreased. Administration of AF caused hepatotoxicity, cardiotoxicity, and
      nephrotoxicity. As far as histopathological changes are concerned, a
      statistically significant difference was found in AFB1 group compared to the
      control group. Vit E considerably reduced plasma AST, ALT, ALP, LDH activities,
      and urea concentration and ameliorated the deleterious effects of AF on oxidative
      stress markers and pathological changes. CONCLUSIONS: This data indicated that
      the natural antioxidant Vit E might have a protective effect against AF-induced
      toxicity and oxidative stress.

PMID- 29068591
TI  - Effect of nebivolol on fracture healing: An experimental rat model.
AB  - BACKGROUND: Bone metabolism is a complex system, and fracture healing is one of
      its most important functions. Many circumstances can influence this process.
      Chronic drug use in elderly populations can affect bone healing, and inadequate
      tissue perfusion, increased free radicals and adverse drug effects can negatively
      influence fracture healing. Nebivolol, an anti-hypertensive drug that selectively
      blocks beta1 receptors, effectively reduces blood pressure by inducing peripheral
      vasodilation. Nebivolol also exerts anti-oxidant effects by stimulating nitric
      oxide (NO) synthesis. Many studies show that NO protects the vascular endothelium
      and improves fracture healing. OBJECTIVES: In this study, the histological and
      radiological effects of intraperitoneally administered nebivolol on fracture
      healing were evaluated. MATERIAL AND METHODS: Twenty-one Sprague Dawley rats were
      divided into 3 (nebivolol 1, 2 and control) groups. Sterile nebivolol solution (1
      mL = 0.017 mg nebivolol) was given to the rats in group 1 every day for 4 weeks,
      while the rats in nebivolol group 2 were given 2 mL per day, beginning after the
      production of an open, displaced unilateral femur fracture. Radiographic and
      histological studies were used to evaluate fracture healing. RESULTS:
      Histological and immunohistochemical analysis showed osseous healing with woven
      bone at the fracture site and only minimal amounts of cartilage in nebivolol 1
      and 2 groups. Radiological grading was not different between the control and the
      nebivolol groups. CONCLUSIONS: This study suggests that nebivolol, a selective
      beta blocker, has positive effects on fracture healing through anti-oxidative
      effects via the NO pathway and direct vasodilator effects.

PMID- 29068592
TI  - The effects of crocin on the symptoms of depression in subjects with metabolic
      syndrome.
AB  - BACKGROUND: Studies have suggested that metabolic syndrome (MetS) is associated
      with increased depressive symptoms, and reducing depression in subjects with MetS
      is important. Crocin, an active component of saffron, has useful properties for
      subjects with MetS, including antidepressant properties. OBJECTIVES: The aim of
      the study was to assess the effect of a preparation of crocin on the symptoms of
      depression in subjects with MetS, and the relationship between changes in those
      symptoms and the serum pro-oxidant/anti-oxidant balance (PAB). MATERIAL AND
      METHODS: This sub-study was carried out on 34 subjects with MetS from the
      authors' previous randomized double-blind controlled clinical trial (RCT), all of
      whom met the inclusion criteria for this study. The subjects were randomly
      assigned to treatment and placebo groups (n = 17 in each group) and received each
      30 mg of crocin (2 tablets of 15 mg) or placebo for 8 weeks. Depressive symptoms
      were assessed using the Beck Depression Inventory (BDI). The BDI questionnaire
      was completed for each subject at the baseline and at the end of the 8th week of
      treatment. Blood samples were taken from the subjects before and after the
      intervention period. Statistical analyses were performed using the SPSS for
      Windows, v. 16 (SPSS Inc., Chicago, USA). RESULTS: Out of the 34 participants
      enrolled, 33 completed the trial. The degree of depression decreased
      significantly in the crocin group (p = 0.005), but not in the placebo group (p >
      0.05), and the difference between the 2 groups was statistically significant (p =
      0.013). No significant relationship was observed between changes in depression
      symptoms and changes in the serum PAB (p > 0.05). CONCLUSIONS: This study
      demonstrates that at a dose of 30 mg per day for 8 weeks, crocin reduced the
      symptoms of depression in subjects with MetS compared to the control group, and
      this effect was independent of its effect on the serum PAB.

PMID- 29068593
TI  - Soluble ST2 protein and hospitalizations due to worsening chronic heart failure
      during a one-year follow-up in a population with reduced ejection fraction.
AB  - BACKGROUND: Hospitalizations due to worsening chronic heart failure (CHF) are
      common. However, the relationship between a single measurement of soluble ST2
      protein (sST2) and the necessity of hospitalization in CHF is still unclear.
      OBJECTIVES: The aim of this study was to determine the association between a
      single measurement of sST2 concentration and hospitalizations due to worsening
      CHF during a one-year follow-up. MATERIAL AND METHODS: The study involved 167
      consecutive patients (mean age 63 years, 83% males) with CHF in stable NYHA
      classes I-III with left ventricular ejection fraction (LVEF) <= 45% (median
      29.65%, range 13-45%). Fifty-six variables were analyzed (clinical factors, basic
      laboratory results on admission, standard 12-lead ECG, echocardiography and
      coronary arteriography results). Information about hospitalizations due to
      worsening CHF was obtained during telephone interviews conducted 12 months after
      discharge from the cardiac ward. In order to define factors associated with
      hospitalization, uniand multivariate regression analyses were performed. RESULTS:
      A total of 53 patients from the study group (38%) were hospitalized due to
      worsening CHF. They included a higher percentage of males (p = 0.042), higher
      concentrations of sST2 (p = 0.049), and glucose (p = 0.010). The multivariate
      analysis (for model chi2 = 17.235; p < 0.001) revealed that glucose and sST2 were
      independently associated with hospitalization due to worsening CHF during the 1
      year observation (p < 0.001). CONCLUSIONS: In patients with stable mild to
      moderate CHF with reduced EF, a single measurement of sST2 protein and glucose
      were independent variables for hospitalization due to worsening CHF over a 1-year
      follow-up period. The defined prognostic model including sST2 and fasting glucose
      better identified patients without HF-related hospitalizations.

PMID- 29068594
TI  - Oxidative damage of DNA in subjects occupationally exposed to lead.
AB  - BACKGROUND: Exposure to lead (Pb) in environmental and occupational settings
      continues to be a serious public health problem and may pose an elevated risk of
      genetic damage. OBJECTIVES: The aim of this study was to assess the level of
      oxidative stress and DNA damage in subjects occupationally exposed to lead.
      MATERIAL AND METHODS: We studied a population of 78 male workers exposed to lead
      in a lead and zinc smelter and battery recycling plant and 38 men from a control
      group. Blood lead levels were detected by graphite furnace atomic absorption
      spectrophotometry and plasma lead levels by inductively coupled plasma-mass
      spectrometry. The following assays were performed to assess the DNA damage and
      oxidative stress: comet assay, determination of 8-hydroxy-2'-deoxyguanosine (8
      OHdG), lipid peroxidation and total antioxidant status (TAS). RESULTS: The mean
      concentration of lead in the blood of the exposed group was 392 +/- 103 MUg/L and
      was significantly higher than in the control group (30.3 +/- 29.4 MUg/L, p <
      0.0001). Oxidative DNA damages measured by comet assay showed no significant
      differences between populations. The concentration of 8-OHdG was about twice as
      high as in the control group. We found a significant positive correlation between
      the level of biomarkers of lead exposure [lead in blood, lead in plasma, zinc
      protoporphyrin (ZPP)] and urine concentration of 8-OHdG. The level of oxidative
      damage of DNA was positively correlated with the level of lipid peroxidation
      (TBARS) and negatively with total anti-oxidative status (TAS). CONCLUSIONS: Our
      study suggests that occupational exposure causes an increase in oxidative damage
      to DNA, even in subjects with relatively short length of service (average length
      of about 10 years). 8-OHdG concentration in the urine proved to be a sensitive
      and non-invasive marker of lead induced genotoxic damage.

PMID- 29068596
TI  - The evaluation of the changes in enzymatic antioxidant reserves and lipid
      peroxidation in chosen parts of the brain in an animal model of Parkinson
      disease.
AB  - BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder,
      characterized by the loss of dopaminergic neurons in the substantia nigra pars
      compacta. The causes of Parkinson's disease are not fully understood; however,
      increasing evidence implicates oxidative stress. OBJECTIVES: The study was aimed
      at assessing the nature of the changes in the oxidation-antioxidant balance in
      the cerebral cortex, striatum, hippocampus, thalamus, and cerebellum in a rat
      model of Parkinson's disease (PD). MATERIAL AND METHODS: Sixteen male Wistar rats
      were divided into 2 groups: Icontrol, IIParkinson's disease. The 8-weeks-old
      animals were decapitated, their brains removed and the following structures
      dissected and then frozen for further biochemical assays: cerebral cortex,
      striatum, hippocampus, thalamus and cerebellum. The activities of: the catalase
      (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione S
      transferase (GST), superoxide dismutase (SOD) and the isoenzymes: Cu/ZnSOD and
      MnSOD; together with the malondialdehyde (MDA) and the total oxidative status
      (TOS) concentrations were measured in each structure. RESULTS: A significantly
      increased activities of SOD, Cu/ZnSOD, GST and reduced GR activity and an
      increase of MDA concentration were observed in the striatum of PD rats, comparing
      to the control group, combined with a significantly reduced activities of GR,SOD,
      Cu/ZnSOD and an increased GPX activity and MDA concentration in the hippocampus,
      a significantly lower GR, SOD, MnSOD, Cu/ZnSOD, and GST activities in the
      cerebral cortex. A significantly lower GR activity, higher CAT activity and MDA
      concentration in the thalamus and a significantly increased GR activity in the
      cerebellum were observed in PD rats compared to the corresponding control group.
      CONCLUSIONS: Oxidative stress in PD involves many brain structures and various
      antioxidant enzymes and oxidative status parameters become dysfunctional,
      depending on the area of the brain, which might reflect the complexity of the
      clinical symptoms of PD.

PMID- 29068595
TI  - Computational fluid dynamics in the assessment of patients' postoperative status
      after glottis-widening surgery.
AB  - BACKGROUND: Computational fluid dynamics (CFD), a rapidly developing instrument
      with a number of practical applications, allows calculation and visualization of
      the changing parameters of airflow in the upper respiratory tract. OBJECTIVES:
      The aim of this study was to demonstrate the advantages of CFD as an instrument
      for noninvasive tests of the larynx in patients who had undergone surgical
      treatment due to bilateral vocal fold paralysis. MATERIAL AND METHODS: Surface
      measurements of the glottic space were made during maximum adduction of the vocal
      folds. Additionally, the following spirometric parameters were determined: forced
      vital capacity (FVC), forced expiratory volume in the first second (FEV1), and
      peak expiratory flow (PEF) rate. Based on the measurements, commercial mesh
      generation software was used to develop a geometrical model of the glottic space.
      The computations were carried out using a general purpose CFD code. The analysis
      included patients who were surgically treated for BVFP in the authors' department
      between 1999 and 2012. The study group consisted of 22 women (91.67%) and 2 men
      (8.33%). RESULTS: It was observed that the pressure drop calculated for free
      breathing depends on the area of the glottis and is independent of its shape.
      Importantly, for areas below approx. 40 mm2, a sudden rise occurred in the
      resistance to flow; for the smallest glottic areas studied, the pressure drop was
      almost 6 times higher than for an area of 40 mm2. Consequently, in cases of areas
      below 40 mm2 even minor enlargement of the glottic opening can lead to a marked
      improvement in breathing comfort. CONCLUSIONS: Computational fluid dynamics is a
      useful method for calculating and visualizing the changing parameters of airflow
      in the upper respiratory tract.

PMID- 29068597
TI  - Gene expression profile of collagen types, osteopontin in the tympanic membrane
      of patients with tympanosclerosis.
AB  - BACKGROUND: Tympanosclerosis is a pathological process involving the middle ear.
      The hallmark of this disease is the formation of calcium deposits. In the
      submucosal layer, as well as in the right layer of the tympanic membrane, the
      calcium deposits result in a significant increase in the activity of fibroblasts
      and deposition of collagen fibers. OBJECTIVES: The aim of our study was to
      examine the expression level of genes encoding collagen type I, II, III and IV
      (COL1A1, COL2A1, COL3A1, COL4A1) and osteopontin (SPP1) in the tympanic membrane
      of patients with tympanosclerosis. MATERIAL AND METHODS: The total RNA was
      isolated from middle ear tissues with tympanosclerosis, received from 25 patients
      and from 19 normal tympanic membranes. The gene expression level was determined
      by real-time RT-PCR. The gene expression levels were correlated with clinical Tos
      classification of tympanosclerosis. RESULTS: We observed that in the tympanic
      membrane of patients with tympanosclerosis, the expression of type I collagen is
      decreased, while the expression of type II and IV collagen and osteopontin is
      increased. Moreover, mRNA levels of the investigated genes strongly correlated
      with the clinical stages of tympanosclerosis. CONCLUSIONS: The strong
      correlations between the expression of type I, II, IV collagen and osteopontin
      and the clinical stage of tympanosclerosis indicate the involvement of these
      proteins in excessive fibrosis and pathological remodeling of the tympanic
      membrane. In the future, a treatment aiming to modulate these gene expressions
      and/or regulation of the degradation of their protein products could be used as a
      new medical approach for patients with tympanosclerosis.

PMID- 29068598
TI  - The sequence of lanugo pattern development on the trunk wall in human fetuses.
AB  - BACKGROUND: Due to a growing interest in developmental disorders, and in the long
      term skin appendage diseases, both in the cosmetic industry and among specialists
      in dermatology (broadly defined), there is an increasing number of papers on hair
      development. The publications by the present team of authors are part of this
      trend. OBJECTIVES: The aim of the study was to describe the topography and
      typology of skin pilosity patterns in human fetuses. MATERIAL AND METHODS: A
      total of 278 fetuses (141 male and 137 female) were qualified for the study. The
      gestational age ranged from 69 to 226 days after conception. All fetuses were
      taken from a local collection. RESULTS: The study revealed that the first single
      hairs occur on the posterior wall of the trunk in the 17th week of fetal life,
      and on the anterior wall between the 18th and 19th week. It was found that in
      human fetuses lanugo appears statistically significantly later on the skin of the
      anterior of the trunk than on its posterior. The difference in absolute time is
      almost 2 weeks of fetal life. No other differences were found in the development
      cycle of lanugo on the anterior and posterior walls of the trunk. A full pattern
      was first observed on the posterior wall of the trunk in a fetus in the 19th
      week, and on the anterior wall in the 21st week. It was found that the process of
      lanugo development was completed on the posterior wall in the 23rd week, and on
      the surface of the abdomen in the 26th week. CONCLUSIONS: The lanugo
      developmental cycle, consisting in the appearance of the first single hairs, then
      partial hair and subsequently the formation of final patterns, is the same on
      both walls of the trunk.

PMID- 29068599
TI  - Body composition in 13-year-old adolescents with abdominal obesity, depending on
      the BMI value.
AB  - BACKGROUND: Excessive adipocyte growth during the pubertal transition predisposes
      to the development and persistence of obesity in adulthood. Visceral accumulation
      of body fat is particularly disadvantageous when it is correlated with insulin
      resistance, secondary hyperinsulinaemia, dysglicaemia, and atherogenic
      dyslipidemia. OBJECTIVES: The aim of this study was to conduct a nutritional
      status assessment and body composition analysis in 13-year-old adolescents of
      both genders with visceral fat accumulation (WC >= 90th percentile) and different
      BMI values. MATERIAL AND METHODS: The evaluation of state of nutrition of 1,738
      Polish boys (n = 882) and girls (n = 856) aged 13 was done based on
      anthropometric measurements and calculated BMI (body mass index), WC (waist
      circumference) and WHtR indices (waist-to-height ratio). Taking into
      consideration the value of WC >= 90 pc, 353 people were designated (20.3 % of the
      total) with visceral obesity (but with various BMI), whose body composition was
      examined by the method of bioelectric impedance analysis (BIA). A total of 249
      adolescents of both sexes (70.5% of the selected, 102 boys and 147 girls) and
      their parents agreed to the study. RESULTS: In adolescents with visceral obesity
      a significant change of body content was ascertained depending on the value of
      the BMI. Even in the people with a proper value of the BMI, a significantly
      higher than standard increase of the percentage of total body fat (TBF) and
      decrease of both the percentage of body lean (BL) and the content of total body
      water (TBW) in the body was observed. The values of the BMI, WC and WHtR in
      adolescents were significantly correlated with each other as well as with TBF, BL
      and TBW, and the strength of correlation was dependent on sex. CONCLUSIONS: The
      state of nutrition in adolescents with visceral obesity, even with a proper BMI,
      might contribute to the development of a metabolic syndrome.

PMID- 29068600
TI  - Application of the functional capacity scale in the early assessment of
      functional efficiency in patients after aneurysm embolization: Preliminary
      reports.
AB  - BACKGROUND: While data on the long-term (e.g., 1 year and subsequent years)
      outcomes of intracranial aneurysms treatment is relatively well-documented mainly
      in the clinical aspect (comparability of treatment, mortality, and
      complications), little is known about the early results, in terms of the
      functional outcome. OBJECTIVES: The aim of the study was to analyze the use of
      Functional Capacity Scale (FCS) in the evaluation of patients in the early period
      after endovascular treatment of intracranial aneurysms. MATERIAL AND METHODS: The
      study was conducted in the Neurosurgery Clinic, University Hospital Collegium
      Medicum in Bydgoszcz, on a group of 118 consecutively admitted patients with the
      diagnosis of intracranial aneurysm, qualified for treatment using the
      endovascular method (embolization). The assessment was performed twice. In the
      clinical assessment the Glasgow Coma Scale (GCS) was used to evaluate the level
      of consciousness and the Hunt and Hess Scale (H&H) to assess the patient's
      condition. To assess the final outcome and early functional capacity Glasgow
      Outcome Scale (GOS), Barthel Index (BI), Modified Rankin Scale (mRS) and the new
      Functional Capacity Scale were used. RESULTS: The assessment performed with the
      FCS was comparable to the assessment conducted with standardized tools such as
      BI, mRS or GOS. The clinical condition assessed with the GCS (p < 0.001) and H&H
      (p < 0.001) differentiates the functional condition assessed using the FCS.
      Statistically significant correlations were found between FCS and BI (r = -0.78),
      GOS (r = -0.69) and mRS (r = 0.68). CONCLUSIONS: The study indicates that the FCS
      correlates with other scales used in the assessment of patients with intracranial
      aneurysm, which means that the proposed tool can be applied successfully in
      practice. However, further randomized multicenter studies are necessary in order
      to clarify the final conclusion.

PMID- 29068601
TI  - Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies
      with hepatitis B and hepatitis C infection: Review.
AB  - BACKGROUND: Viruses are common and are involved in the etiology of idiopathic
      rheumatological diseases. Hepatitis B virus (HBV), a member of the family
      Hepadnaviridae and hepatitis C virus (HCV), play an important role in the
      undetermined etiology of arthritis. The clinical manifestations of hepatitis B
      and C show similarities with various diseases, such as rheumatic diseases. Anti
      cyclic citrullinated peptide (anti-CCP) is a specific serological marker for
      rheumatoid arthritis. OBJECTIVES: The aim of this study was to analyze anti-CCP
      and rheumatoid factor (RF) levels in patients with a hepatitis B and C infection.
      MATERIAL AND METHODS: Forty-four patients with hepatitis B, 43 patients with
      hepatitis C, 25 patients with rheumatoid arthritis, and 46 healthy control serums
      and their RF and anti-CCP levels were compared. RF was measured by the
      nephelometer, which detects IgM-RF. Anti-CCP was measured using enzymelinked
      immunosorbent assay (ELISA) that is included in the second-generation anti-CCP
      antibody assays (anti-CCP2). RESULTS: The anti-CCP positivity levels were 20.5%,
      32.5%, 72.4% and 10.9% for HBV, HCV and RA groups and healthy control group,
      respectively. When the groups were compared based on their RF positivity and anti
      CCP positivity while the values for HBV and HCV group and healthy control group
      were the same, in RA group there is a significant difference to the rest of the
      groups (p < 0.01). CONCLUSIONS: Anti-CCP may be positive for HBV and HCV as well,
      but it is a sensitive and specific immunological marker for RA diagnosis,
      especially in high-titres.

PMID- 29068602
TI  - Filaggrin loss-of-function mutations as a predictor for atopic eczema, allergic
      sensitization and eczema-associated asthma in Polish children population.
AB  - BACKGROUND: Loss-of-function mutations in the filaggrin (FLG) gene were
      identified as a major risk factor for atopic eczema. OBJECTIVES: The aim of the
      study was to investigate the importance of 4 common FLG null mutations in the
      susceptibility to atopic eczema and other allergic phenotypes in Polish children
      population. MATERIAL AND METHODS: The FLG mutations were determined in 158
      children younger than 2 years of age. All subjects were selected using a detailed
      questionnaire and blood samples for total and specific IgE measurements were
      obtained. Cases of atopic eczema were diagnosed according to the criteria of
      Hanifin and Rajka and skin examination. All FLG mutations were genotyped by real
      time PCR assays with a subsequent melting curve analysis using a SimpleProbe(r)
      probes. RESULTS: The combined genotype of all 4 mutations (carriage of >= 1 FLG
      mutation) was significantly associated with atopic eczema (p = 0.016). The odds
      ratio (OR) for individuals carrying 1 of these 4 null mutations was 5.52 (95% CI;
      1.11 / 37.12). The significant association between either the combined FLG
      genotype or 2282del14 deletion and eczema was seen only in the allergic group.
      The association with asthma was restricted to asthma occurring in the context of
      eczema (OR, 6.27; 95% CI, 0.89 / 53.56; p = 0.042). CONCLUSIONS: Our study
      confirms the previous findings that FLG mutations are strongly associated with
      atopic eczema and confer a significant risk of allergic sensitization and asthma
      in the context of eczema. These results underline the role of the epidermal
      barrier and filaggrin insufficiency in the pathogenesis of atopic eczema and
      eczema-associated asthma.

PMID- 29068603
TI  - Differences in echocardiography, blood pressure, stroke volume, maximal power and
      profile of genes related to cardiac hypertrophy in elite road cyclists.
AB  - BACKGROUND: Regular and moderate exercise is beneficial for improving the
      efficiency of the heart, but high-intensity physical activity may result in
      cardiac changes. OBJECTIVES: This study focuses on the identification of the
      differences in echocardiography and blood variables before exercise, as well as
      the genes associated with cardiac hypertrophy at rest and in response to graded
      exercise test. MATERIAL AND METHODS: The study group was made up of 28 road
      cyclists. Echocardiographic parameters and blood pressure were measured before
      exercise tests (N = 28). Blood samples were collected at rest, at maximal
      exercise intensity in a graded bicycle test and after 15 min of recovery;
      afterwards, blood morphology was estimated and RNA was isolated. Analysis of the
      expression profile of genes was performed for randomly selected road cyclists
      using the microarray method. RESULTS: Echocardiographic results and blood
      parameters divided cyclists into two groups: with and without left ventricular
      hypertrophy (N = 14). Differences in the structure and function of the left
      ventricle cyclists with a similar level of training were observed (p < 0.05).
      Diastolic blood pressure and resting heart rate were significantly lower in
      subjects with left ventricular hypertrophy (p < 0.05). The myosin light chain 9
      and interleukin-6 signal transducer gene expression were differentially regulated
      in cyclists with left ventricular hypertrophy compared to athletes with normal
      heart dimensions in response to intensive exercise. CONCLUSIONS: We have found
      differences in echocardiography parameters, blood pressure, stroke volume and
      maximal power in the cyclists examined. These studies indicate the benefits of
      the recommended echocardiography measurements for professional endurance
      athletes. The graded exercise altered the myosin light chain 9 and interleukin-6
      signal transducer gene expression in the peripheral blood of road cyclists has
      also been found.

PMID- 29068604
TI  - Clinical factors in prosthodontic treatment of children with genetic defects.
AB  - BACKGROUND: Prosthodontic treatment of children with genetic disorders is an area
      that is rarely examined in the current specialist literature. Few prosthodontists
      will undertake treatment of such patients, who will more often be referred to an
      orthodontic specialist. After examining the 4 cases of children with genetic
      disorders described in this paper, it can be concluded that when a prosthodontist
      includes a few additional procedures in the treatment process, he or she can
      successfully help such patients. OBJECTIVES: The aim of this paper is to indicate
      the clinical difficulties faced by prosthodontists who undertake prosthodontic
      rehabilitation of children with genetic disorders. MATERIAL AND METHODS: The
      paper is based on data collected during the prosthodontic treatment of 4
      children, aged 5-12 years with genetic defects, and analysis of the body of work
      concerning these defects and their treatment. RESULTS: Presentation of guidelines
      for the prosthodontic treatment process and creation of dentures for treated
      children based on extended procedures. CONCLUSIONS: A prosthodontist is a crucial
      person in a team of specialists treating disorders within the face among children
      with a genetic predisposition. A basic knowledge of orthodontics and psychology
      facilitates the treatment. Prosthetic restoration in the treatment group does not
      always require complicated operations. Individualization of the tools for
      downloading orthodontic impressions, designing denture elements and an increased
      number of checkups are the additional procedures. For the clinician, the
      emotional aspect of the treatment is the main impediment. Maintaining a good
      relationship with a patient and his or her caregivers requires interpersonal
      skills.

PMID- 29068605
TI  - The potential role of selected bioactive compounds from spelt and common wheat in
      glycemic control.
AB  - Diet is an important lifestyle factor which influences people's health and the
      prevention of chronic diseases such as type 2 diabetes. Cereal-based foods
      constitute the main component of the everyday diet worldwide. Old cereal species
      like spelt (Triticum spelta L.) are becoming more and more popular, especially in
      Europe. This review focuses on the role of bioactive compounds from spelt and
      their possible biological mechanisms of action in glycemic control. Spelt grain
      contains a high amount of dietary fiber, which can modulate postprandial
      glycemia. Other phytochemicals, such as phytic acid and alkylresorcinols, also
      contribute to controlling blood glucose levels, insulin sensitivity and
      hiperinsulinemia. Antioxidant compounds present in spelt grain may act as
      protection from negative outcomes of chronic hyperglycemia. In this paper the
      composition and beneficial properties of spelt are also compared with those of
      widely consumed cereals like common wheat (Triticum aestivum L.). The health
      benefits of whole grain as opposed to refined products are also discussed.

PMID- 29068606
TI  - Salivary lipids: A review.
AB  - Saliva is produced by both large and small salivary glands and may be considered
      one of the most important factors influencing the behavior of oral cavity
      homeostasis. Secretion of saliva plays an important role in numerous significant
      biological processes. Saliva facilitates chewing and bolus formation as well as
      performs protective functions and determines the buffering and antibacterial
      prosperities of the oral environment. Salivary lipids appear to be a very
      important component of saliva, as their qualitative and quantitative composition
      can be changed in various pathological states and human diseases. It has been
      shown that disturbances in salivary lipid homeostasis are involved in periodontal
      diseases as well as various systemic disorders (e.g. cystic fibrosis, diabetes
      and Sjogren's syndrome). However, little is known about the role and composition
      of salivary lipids and their interaction with other important ingredients of
      human saliva, including proteins, glycoproteins and salivary mucins. The purpose
      of this review paper is to present the latest knowledge on salivary lipids in
      healthy conditions and in oral and systemic diseases.

PMID- 29068608
TI  - Olfactory Hallucinations as the Presenting Symptom in Acute Psychosis.

PMID- 29068607
TI  - Relationship between toxoplasmosis and schizophrenia: A review.
AB  - A growing body of evidence suggests a correlation between schizophrenia and
      exposure to infectious agents. The majority of studied cases concerns the
      infection caused by T. gondii, an obligatory intracellular parasite that infects
      about 1/3 of the entire human population, according to the available data. The
      acute stage of the disease, predominantly short-lived and transient, transforms
      into the latent and chronic phase in which the parasite localizes within tissue
      cysts, mainly in the central nervous system. The chronic toxoplasmosis, primarily
      regarded as benign and asymptomatic, might be responsible, in light of current
      scientific evidence, for a vast array of neuropsychiatric symptoms. Numerous
      epidemiological case-control studies show a higher prevalence of T. gondii
      infestation in individuals with various psychiatric and behavior disorders,
      including schizophrenia. This paper tends to review the relevant studies that
      demonstrate links between schizophrenia and T. gondii infestation, of which the
      latter may be acquired in different developmental phases. Apart from
      epidemiological correlation studies, some papers on other associations were also
      presented, describing putative patophysiological mechanisms that might be at
      least partly responsible for chronic infection-induced neuromediator
      disturbances, together with morphological and functional alterations, e.g., low
      grade neuroinflammation, which are likely to induce psychopathological symptoms.
      Toxoplasmosis is only one of the putative infectious agents that derange correct
      brain growth and differentiation, alongside genetic and environmental factors.
      All of them may lead eventually to schizophrenia. A better knowledge of infection
      mechanisms and its influence on neurobiochemical and neuropathological pathways
      may enable more efficient therapy and the prevention of this devastating disease.

PMID- 29068609
TI  - Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Clozapine.
AB  - BACKGROUND: Schizophrenia is a psychiatric disorder that affects approximately
      0.4%-1% of the population worldwide. Diagnosis of schizophrenia is based
      primarily on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
      (DSM-5) criteria. Clozapine is an antipsychotic drug that is mainly used in the
      treatment of schizophrenia patients who are refractory or intolerant to at least
      2 other antipsychotics. Due to the high variability in pharmacokinetics of
      clozapine, therapeutic drug monitoring (TDM) is highly recommended for clozapine
      therapy. OBJECTIVE: To develop and clinically validate a novel sampling method
      using dried blood spot (DBS) to support TDM of clozapine and norclozapine.
      METHODS: From June 2014 to September 2014, 15 schizophrenia patients (18-55
      years) treated with clozapine were included. Plasma, DBS samples made from venous
      samples (VDBS), and finger prick DBS (DBS) samples were obtained before
      administration and 2, 4, 6, and 8 hours after clozapine intake. The study was
      repeated in 6 Russian patients for external validation. Passing-Bablok regression
      and Bland-Altman analysis were used to compare the DBS, VDBS, and plasma results
      for clozapine and norclozapine. RESULTS: The DBS validation results showed good
      linearity over the concentration time curve measured for clozapine and
      norclozapine. The accuracy and between- and within-day precision variation values
      were within accepted ranges. Different blood spot volumes and hematocrit values
      had no significant influence on the results. The DBS samples were stable at 20
      degrees C and 37 degrees C for 2 weeks and at -20 degrees C for 2 years. The mean
      clozapine and norclozapine DBS/plasma ratios were, respectively, 0.80 (95% CI,
      0.76 to 0.85) and 1.063 (95% CI, 1.027 to 1.099) in Dutch patients. The mean
      clozapine DBS/DPS ratio in Russian patients was 0.70 (95% CI, 0.64 to 0.76).
      CONCLUSION: DBS analysis is a reliable tool for blood sampling and performing TDM
      of clozapine and norclozapine in daily practice and substantially extends the
      opportunities for TDM of clozapine.

PMID- 29068610
TI  - Seizure Risk Associated With Antidepressant Treatment Among Patients With
      Depressive Disorders: A Population-Based Case-Crossover Study.
AB  - OBJECTIVE: To assess the risk of seizure associated with antidepressant use among
      patients with depressive disorders. METHODS: Individuals visiting the emergency
      department or hospitalized because of new-onset seizure (ICD-9-CM diagnostic code
      345 or 780.3; our primary study outcome) after receiving antidepressants for
      depressive disorders, were identified from a Taiwanese total population health
      insurance database. Using a case-crossover study design, relative risk of
      antidepressant-related seizure was estimated by comparing the rates of
      antidepressant exposure during the case periods vs control periods. The effects
      of class and dose of antidepressant on seizure risk were explored, using a
      conditional logistic regression model adjusting for concomitant medications.
      Several sensitivity analyses were conducted to attest the results of primary
      analyses. RESULTS: A total of 10,002 patients were included between 2002 and
      2012. Overall, antidepressant exposure was positively associated with increased
      seizure risk (OR = 1.48, 95% CI, 1.33-1.64). Among the antidepressants, the
      increases in seizure risk of bupropion (OR = 2.23, 95% CI, 1.58-3.16), selective
      serotonin reuptake inhibitors (OR = 1.76, 95% CI, 1.55-2.00), serotonin and
      norepinephrine reuptake inhibitors (OR = 1.40, 95% CI, 1.10-1.78), and
      mirtazapine (OR = 1.38, 95% CI, 1.08-1.77) showed clear dose-response effects.
      Furthermore, the seizure risk was highest among patients aged between 10 and 24
      years and patients with major depression. The results of sensitivity analyses
      largely confirmed those from the primary analyses. CONCLUSIONS: The seizure
      inducing propensity and dose-response relationship pattern, as well as potential
      risk factors, associated with individual antidepressants should be taken into
      consideration when choosing antidepressants during clinical practice.

PMID- 29068612
TI  - Systemic Conditions and Oral Health.

PMID- 29068613
TI  - Ethical Priming.

PMID- 29068611
TI  - Does Patient Adherence to Antidepressant Medication Actually Vary Between
      Physicians?
AB  - OBJECTIVE: Previous research and improvement efforts have presumed that patients'
      nonadherence to antidepressant medication reflects physicians' quality of care.
      We used population-based health records to examine whether adherence to
      antidepressant medication actually varies between prescribing physicians.
      METHODS: Electronic health records and insurance claims data from 5 integrated
      health systems in Washington, Idaho, Minnesota, Colorado, Hawaii, and California
      were used to identify 150,318 adults starting new episodes of antidepressant
      treatment for depression between January 1, 2010, and December 31, 2012. Early
      adherence was defined as any refill or dispensing of antidepressant medication in
      the 180 days following an initial antidepressant prescription. Patient-level
      demographic and clinical characteristics potentially associated with adherence
      were identified from health system records. RESULTS: Average probability of early
      adherence was 82% for psychiatrists and 74% for primary care physicians. Among
      individual physicians, the range of raw or unadjusted early adherence rates (5th
      to 95th percentiles) was from 33% to 100% for psychiatrists and from 0% to 100%
      for primary care physicians. After accounting for sampling variation and case mix
      differences, the range of adjusted early adherence rates (5th to 95th
      percentiles) was from 72% to 78% for psychiatrists and from 64% to 69% for
      primary care physicians. CONCLUSIONS: After accounting for sampling variation and
      case mix differences, early adherence to antidepressant medication varies
      minimally among prescribing physicians. Early discontinuation of antidepressant
      treatment is not an appropriate measure of individual physician performance, and
      efforts to improve adherence should emphasize system-level interventions rather
      than the performance of individual physicians.

PMID- 29068614
TI  - Disparities Found Between Asian Immigrants, Utilization of Dental Services.

PMID- 29068615
TI  - FDA Warns Against Use of Homeopathic Teething Products.

PMID- 29068616
TI  - Genetic Defects in Tooth Enamel Can Lead to Cavities.

PMID- 29068617
TI  - Bacterium 'Lasso' From Mouth to Heart Can Cause Disease.

PMID- 29068618
TI  - Regulatory Pitfalls and How to Avoid Them.

PMID- 29068619
TI  - California Infection Control Regulations for Dental Professionals.
AB  - Infection control regulations that affect dental professionals comefrom several
      regulatory agencies and are increasingly complex. Staying up to dateon changes
      and the overlapping requirements can challenge a busy dental practice.This
      article reviews the current regulations in California and suggests methods
      forensuring every dental office is in compliance.

PMID- 29068620
TI  - Inspections of X-ray Use in Dental Practices and Common Regulatory Violations.
AB  - Dental X-ray machine inspections are conducted by the CaliforniaDepartment of
      Public Health's Radiologic Health Branch (RHB). RHB's missionis to protect public
      health and safety throughout California by ensuring the safeuse of radiologic
      equipment and materials within industry, medicine and research,preventing
      radiologic health hazards and educating and enforcing applicable stateand federal
      radiation laws and regulations.

PMID- 29068623
TI  - The Dental Board of California: The Investigation Process.

PMID- 29068621
TI  - Lowering the Radiation Dose in Dental Offices.
AB  - While the use of dental imaging continues to evolve into more advanced modalities
      such as 3-D cone beam computed tomography, in addition to conventional 2-D
      imaging (intraoral, panoramic and cephalometric), the publicconcern for radiation
      safety is also increasing. This article is a guide for how to reduce patients'
      exposure to the minimum with proper selection criteria (as needed only if it
      benefits the patient) and knowledge of effective doses, exposure parameters and
      proper collimation.

PMID- 29068624
TI  - Pound Foolish: Cost as a Factor in Treatment Decisions.

PMID- 29068625
TI  - Enabling Health Reform through Regional Health Information Exchange: A Model
      Study from China
AB  - Objective: To investigate and share the major challenges and experiences of
      building a regional health information exchange system in China in the context of
      health reform. Methods: This study used interviews, focus groups, a field study,
      and a literature review to collect insights and analyze data. The study examined
      Xinjin's approach to developing and implementing a health information exchange
      project, using exchange usage data for analysis. Results: Within three years and
      after spending approximately $2.4 million (15 million RMB), Xinjin County was
      able to build a complete, unified, and shared information system and many
      electronic health record components to integrate and manage health resources for
      198 health institutions in its jurisdiction, thus becoming a model of regional
      health information exchange for facilitating health reform. Discussion: Costs,
      benefits, experiences, and lessons were discussed, and the unique characteristics
      of the Xinjin case and a comparison with US cases were analyzed. Conclusion: The
      Xinjin regional health information exchange system is different from most of the
      others due to its government-led, government-financed approach. Centralized and
      coordinated efforts played an important role in its operation. Regional health
      information exchange systems have been proven critical for meeting the global
      challenges of health reform.

PMID- 29068626
TI  - Regulatory Compliance Tips for New Dentists.

PMID- 29068627
TI  - Tech Trends. A look into the latest dental and general technology on the market.

PMID- 29068628
TI  - Upper Limb Rehabilitation Robot Powered by PAMs Cooperates with FES Arrays to
      Realize Reach-to-Grasp Trainings
AB  - The reach-to-grasp activities play an important role in our daily lives. The
      developed RUPERT for stroke patients with high stiffness in arm flexor muscles is
      a low-cost lightweight portable exoskeleton rehabilitation robot whose joints are
      unidirectionally actuated by pneumatic artificial muscles (PAMs). In order to
      expand the useful range of RUPERT especially for patients with flaccid paralysis,
      functional electrical stimulation (FES) is taken to activate paralyzed arm
      muscles. As both the exoskeleton robot driven by PAMs and the neuromuscular
      skeletal system under FES possess the highly nonlinear and time-varying
      characteristics, iterative learning control (ILC) is studied and is taken to
      control this newly designed hybrid rehabilitation system for reaching trainings.
      Hand function rehabilitation refers to grasping. Because of tiny finger muscles,
      grasping and releasing are realized by FES array electrodes and matrix scan
      method. By using the surface electromyography (EMG) technique, the subject's
      active intent is identified. The upper limb rehabilitation robot powered by PAMs
      cooperates with FES arrays to realize active reach-to-grasp trainings, which was
      verified through experiments.

PMID- 29068629
TI  - mHealth in emergency medicine [special report]
AB  - With the proliferation of smartphones over the past several years, apps now play
      a prominent role in many social and work contexts, including medicine. This is
      enough of a phenomenon to have inspired the abbreviation "mHealth," short for
      mobile health. The number of app-driven clinical calculators, checklists, and
      risk scores in common use in the emergency department (ED) has significantly
      increased and shows no sign of slowing. Thanks to this digital development and
      innovation, clinical decision support is now just a finger-tap away.As of 2016,
      there were approximately 20,000 apps in the "Medical" category of Apple's app
      store. There are at least 300 apps specifically targeted to emergency clinicians,
      and given the variety of patient presentations, general-purpose apps and apps
      from other specialties likely merit usage in the ED. Despite the abundance of
      apps and their potential to improve patient care, the decision of which apps to
      choose and use is left largely to each clinician, with little guidance on best
      practices or potential risks. The purpose of this report is to educate emergency
      clinicians about medical apps that can be utilized to improve patient care during
      a shift.

PMID- 29068630
TI  - Calculated decisions: Canadian CT Head Injury/Trauma Rule

PMID- 29068631
TI  - Calculated decisions: HEART Pathway for early discharge in acute chest pain

PMID- 29068632
TI  - Calculated decisions: LRINEC Score for necrotizing soft-tissue infection

PMID- 29068633
TI  - Study of the Mechanical Environment of Chondrocytes in Articular Cartilage
      Defects Repaired Area under Cyclic Compressive Loading
AB  - COMSOL finite element software was used to establish a solid-liquid coupling
      biphasic model of articular cartilage and a microscopic model of chondrocytes,
      using modeling to take into account the shape and number of chondrocytes in
      cartilage lacuna in each layer. The effects of cyclic loading at different
      frequencies on the micromechanical environment of chondrocytes in different
      regions of the cartilage were studied. The results showed that low frequency
      loading can cause stress concentration of superficial chondrocytes. Moreover,
      along with increased frequency, the maximum value of stress response curve of
      chondrocytes decreased, while the minimum value increased. When the frequency was
      greater than 0.2 Hz, the extreme value stress of response curve tended to be
      constant. Cyclic loading had a large influence on the distribution of liquid
      pressure in chondrocytes in the middle and deep layers. The concentration of
      fluid pressure changed alternately from intracellular to peripheral in the middle
      layer. Both the range of liquid pressure in the upper chondrocytes and the
      maximum value of liquid pressure in the lower chondrocytes in the same lacunae
      varied greatly in the deep layer. At the same loading frequency, the elastic
      modulus of artificial cartilage had little effect on the mechanical environment
      of chondrocytes.

PMID- 29068634
TI  - Calculated decisions: PERC Rule for pulmonary embolism

PMID- 29068635
TI  - Calculated decisions: Endotracheal Tube (ETT) depth and tidal volume calculator

PMID- 29068636
TI  - Calculated decisions: PECARN pediatric head injury/trauma algorithm

PMID- 29068637
TI  - Calculated decisions: Pediatric Early Warning Score (PEWS)

PMID- 29068638
TI  - Calculated decisions: mMRC (Modified Medical Research Council) Dyspnea Scale

PMID- 29068639
TI  - Calculated decisions: DECAF Score for acute exacerbation of chronic obstructive
      pulmonary disease (COPD)

PMID- 29068640
TI  - Handling Data Skew in MapReduce Cluster by Using Partition Tuning
AB  - The healthcare industry has generated large amounts of data, and analyzing these
      has emerged as an important problem in recent years. The MapReduce programming
      model has been successfully used for big data analytics. However, data skew
      invariably occurs in big data analytics and seriously affects efficiency. To
      overcome the data skew problem in MapReduce, we have in the past proposed a data
      processing algorithm called Partition Tuning-based Skew Handling (PTSH). In
      comparison with the one-stage partitioning strategy used in the traditional
      MapReduce model, PTSH uses a two-stage strategy and the partition tuning method
      to disperse key-value pairs in virtual partitions and recombines each partition
      in case of data skew. The robustness and efficiency of the proposed algorithm
      were tested on a wide variety of simulated datasets and real healthcare datasets.
      The results showed that PTSH algorithm can handle data skew in MapReduce
      efficiently and improve the performance of MapReduce jobs in comparison with the
      native Hadoop, Closer, and locality-aware and fairness-aware key partitioning
      (LEEN). We also found that the time needed for rule extraction can be reduced
      significantly by adopting the PTSH algorithm, since it is more suitable for
      association rule mining (ARM) on healthcare data.

PMID- 29068641
TI  - Pediatric wound care and management in the emergency department [digest].
AB  - Traumatic wounds and lacerations are common pediatric presenting complaints to
      emergency departments. Although there is a large body of literature on wound
      care, many emergency clinicians base management of wounds on theories and
      techniques that have been passed down over time. Therefore, controversial,
      conflicting, and unfounded recommendations are prevalent. This issue reviews
      evidence-based recommendations for wound care and management, including wound
      cleansing and irrigation, anxiolysis/sedation techniques, closure methods, and
      post-repair wound care. [Points & Pearls is a digest of Pediatric Emergency
      Medicine Practice].

PMID- 29068642
TI  - New Directions in 3D Medical Modeling: 3D-Printing Anatomy and Functions in
      Neurosurgical Planning
AB  - This paper illustrates the feasibility and utility of combining cranial anatomy
      and brain function on the same 3D-printed model, as evidenced by a neurosurgical
      planning case study of a 29-year-old female patient with a low-grade frontal-lobe
      glioma. We herein report the rapid prototyping methodology utilized in
      conjunction with surgical navigation to prepare and plan a complex neurosurgery.
      The method introduced here combines CT and MRI images with DTI tractography,
      while using various image segmentation protocols to 3D model the skull base,
      tumor, and five eloquent fiber tracts. This 3D model is rapid-prototyped and
      coregistered with patient images and a reported surgical navigation system,
      establishing a clear link between the printed model and surgical navigation. This
      methodology highlights the potential for advanced neurosurgical preparation,
      which can begin before the patient enters the operation theatre. Moreover, the
      work presented here demonstrates the workflow developed at the National
      University Hospital of Iceland, Landspitali, focusing on the processes of anatomy
      segmentation, fiber tract extrapolation, MRI/CT registration, and 3D printing.
      Furthermore, we present a qualitative and quantitative assessment for fiber tract
      generation in a case study where these processes are applied in the preparation
      of brain tumor resection surgery.

PMID- 29068644
TI  - Research on Safety and Compliance of a New Lower Limb Rehabilitation Robot
AB  - The lower limb rehabilitation robot is an application of robotic technology for
      stroke people with lower limb disabilities. A new applicable and effective
      sitting/lying lower limb rehabilitation robot (LLR-Ro) is proposed, which has the
      mechanical limit protection, the electrical limit protection, and the software
      protection to prevent the patient from the secondary damage. Meanwhile, as a new
      type of the rehabilitation robots, its hip joint rotation ranges are different in
      the patient sitting training posture and lying training posture. The mechanical
      leg of the robot has a variable workspace to work in both training postures. So,
      if the traditional mechanical limit and the electrical limit cannot be used in
      the hip joint mechanism design, a follow-up limit is first proposed to improve
      the compatibility of human-machine motion. Besides, to eliminate the accident
      interaction force between the patient and LLR-Ro in the process of the passive
      training, an amendment impedance control strategy based on the position control
      is proposed to improve the compliance of the LLR-Ro. A simulation experiment and
      an experiment with a participant show that the passive training of LLR-Ro has
      compliance.

PMID- 29068643
TI  - Diagnosis and management of acute exacerbation of chronic obstructive pulmonary
      disease [digest].
AB  - Acute exacerbation of chronic obstructive pulmonary disease (COPD) is a clinical
      diagnosis that is based on changes in dyspnea, cough, and/or sputum production in
      a COPD patient; however, patients presenting with an acute exacerbation may be
      undiagnosed or have a variety of comorbid conditions that can complicate
      diagnosis. This issue presents strategies and algorithms for the early use of
      evidence-based interventions, including appropriate use of antibiotics,
      bronchodilators, and corticosteroids, along with noninvasive ventilation with
      capnography, to minimize morbidity and mortality associated with this disease.
      [Points & Pearls is a digest of Emergency Medicine Practice.].

PMID- 29068656
TI  - A Strain Feedback Compensation Method during Cell Tensile Experiments
AB  - Cell tensile technique is an important and widely used tool in cell mechanical
      research. However, the strain control condition in traditional tensile
      experiments is not satisfied and would result in big errors. These strain errors
      will seriously impact the experimental accuracy and decrease the reliability and
      comparability of experimental results. In order to achieve the accurate strain
      control of the membrane during stretching, a strain feedback compensation method
      based on the digital image correlation is proposed in this paper. To evaluate the
      effect of the proposed compensation method, a series of stretching experiments in
      different strains ranging from 5% to 20% were performed. The results showed that
      our proposed method significantly decreased the errors of strain control. These
      results indicate that the strain feedback compensation method is very effective
      in controlling strain and can greatly improve the experimental accuracy.

PMID- 29068657
TI  - Non-Continuum Intercalated Water Diffusion Explains Fast Permeation through
      Graphene Oxide Membranes.
AB  - Recent experimental studies have revealed unconventional phase and transport
      behaviors of water confined within lamellar graphene oxide membranes, which hold
      great promise not only in improving our current understanding of nanoconfined
      water but also in developing high-performance filtration and separation
      applications. In this work, we explore molecular structures and diffusive
      dynamics of water intercalated between graphene or graphene oxide sheets. We
      identify the monolayer structured water between graphene sheets at temperature T
      below Tc = ~315 K and an interlayer distance d = 0.65 nm, which is absent as the
      sheets are oxidized. The non-continuum collective diffusion of water
      intercalation between graphene layers facilitates fast molecular transport due to
      reduced wall friction. This solid-like structural order of intercalated water is
      disturbed as T or d increases to a critical value, with abnormal declines in the
      coefficients of collective diffusion. Based on a patched model of graphene oxide
      sheets consisting of spatially distributed pristine and oxidized regions, we
      conclude that the non-continuum collective diffusion of intercalated water can
      explain fast water permeation through graphene oxide membranes as reported in
      recent experimental studies, in stark contrast to the conventional picture of
      pressure-driven continuum flow with boundary slip, which has been widely adopted
      in literature but may apply only at high humidity or in the fully hydrated
      conditions.

PMID- 29068658
TI  - Metal-Organic Framework "Swimmers" with Energy-Efficient Autonomous Motility.
AB  - Placed at a water/air interface, particles of porphyrin-based MOFs (metal-organic
      frameworks) cut from large-area films display efficient, multiple-use autonomous
      motility powered by release of solvents incorporated in the MOF matrix and
      directionality dictated by their shapes. The particles can be refueled multiple
      times and can achieve speeds of ca. 200 mm.s-1 with high kinetic energy per unit
      of chemical "fuel" expended (>50 MUJ.g-1). Efficiency of motion depends on the
      nature of the fuel used as well as the microstructure and surface wettability of
      the MOF surface. When multiple movers are present at the interface, they organize
      into "open" structures that exhibit collective, time-periodic motions.

PMID- 29068659
TI  - Interfacial Interactions in van der Waals Heterostructures of MoS2 and Graphene.
AB  - Interfacial coupling between neighboring layers of van der Waals heterostructures
      (vdWHs), formed by vertically stacking more than two types of two-dimensional
      materials (2DMs), greatly affects their physical properties and device
      performance. Although high-resolution cross-sectional scanning tunneling electron
      microscopy can directly image the atomically sharp interfaces in the vdWHs, the
      interfacial coupling and lattice dynamics of vdWHs formed by two different types
      of 2DMs, such as semimetal and semiconductor, are not clear so far. Here, we
      report the ultralow-frequency Raman spectroscopy investigation on interfacial
      couplings in the vdWHs formed by graphene and MoS2 flakes. Because of the
      significant interfacial layer-breathing couplings between MoS2 and graphene
      flakes, a series of layer-breathing modes with frequencies dependent on their
      layer numbers are observed in the vdWHs, which can be described by the linear
      chain model. It is found that the interfacial layer-breathing force constant
      between MoS2 and graphene, alpha0?(I) = 60 * 1018 N/m3, is comparable with the
      layer-breathing force constant of multilayer MoS2 and graphene. The results
      suggest that the interfacial layer-breathing couplings in the vdWHs formed by
      MoS2 and graphene flakes are not sensitive to their stacking order and twist
      angle between the two constituents. Our results demonstrate that the interfacial
      interlayer coupling in vdWHs formed by two-dimensional semimetals and
      semiconductors can lead to new lattice vibration modes, which not only can be
      used to measure the interfacial interactions in vdWHs but also is beneficial to
      fundamentally understand the properties of vdWHs for further engineering the
      vdWHs-based electronic and photonic devices.

PMID- 29068660
TI  - Highly Efficient Dual Active Palladium Nanonetwork Electrocatalyst for Ethanol
      Oxidation and Hydrogen Evolution.
AB  - Tunable palladium nanonetwork (PdNN) has been developed for catalyzing ethanol
      oxidation reaction (EOR) and hydrogen evolution reaction (HER) in alkaline
      electrolyte. 3D PdNN is regarded as a dual active electrocatalyst for both EOR
      and HER for energy conversion application. The PdNN has been synthesized by the
      simple chemical route with the assistance of zinc precursor and a surfactant
      (i.e., cetyltrimethylammonium bromide, CTAB). The thickness of the network can be
      tuned by simply adjusting the concentration of CTAB. Both EOR and HER have been
      performed in an alkaline electrolyte, and characterized by different voltammetric
      methods. The 3D PdNN has shown 2.2-fold higher electrochemical surface area than
      the commercially available Pt/C including other tested catalysts with minimal Pd
      loading. As a result, it provides a higher density of EOR and HER active sites
      and facilitated the electron transport. For example, it shows 2.6-fold higher
      mass activity with significantly lower CO2 production for EOR and the similar
      overpotential (110 mV @ 10 mA cm-2) for HER compared to Pt/C with better reaction
      kinetics for both reactions. Thus, the PdNN is proved as an efficient
      electrocatalyst with better electrocatalytic activity and stability than state-of
      the-art Pt/C for both EOR and HER because of the crystalline, monodispersed, and
      support-free porous nanonetwork.

PMID- 29068661
TI  - Optospintronics in Graphene via Proximity Coupling.
AB  - The observation of micrometer size spin relaxation makes graphene a promising
      material for applications in spintronics requiring long-distance spin
      communication. However, spin dependent scatterings at the contact/graphene
      interfaces affect the spin injection efficiencies and hence prevent the material
      from achieving its full potential. While this major issue could be eliminated by
      nondestructive direct optical spin injection schemes, graphene's intrinsically
      low spin-orbit coupling strength and optical absorption place an obstacle in
      their realization. We overcome this challenge by creating sharp artificial
      interfaces between graphene and WSe2 monolayers. Application of circularly
      polarized light activates the spin-polarized charge carriers in the WSe2 layer
      due to its spin-coupled valley-selective absorption. These carriers diffuse into
      the superjacent graphene layer, transport over a 3.5 MUm distance, and are
      finally detected electrically using Co/h-BN contacts in a nonlocal geometry.
      Polarization-dependent measurements confirm the spin origin of the nonlocal
      signal. We also demonstrate that such signal is absent if graphene is contacted
      to bilayer WSe2 where the inversion symmetry is restored.

PMID- 29068662
TI  - Structural and Optical Properties of Single- and Few-Layer Magnetic Semiconductor
      CrPS4.
AB  - Atomically thin binary two-dimensional (2D) semiconductors exhibit diverse
      physical properties depending on their composition, structure, and thickness. By
      adding another element in these materials, which will lead to formation of
      ternary 2D materials, the property and structure would greatly change and
      significantly expanded applications could be explored. In this work, we report
      structural and optical properties of atomically thin chromium thiophosphate
      (CrPS4), a ternary antiferromagnetic semiconductor. Its structural details were
      revealed by X-ray and electron diffraction. Transmission electron microscopy
      showed that preferentially cleaved edges are parallel to diagonal Cr atom rows,
      which readily identified their crystallographic orientations. Strong in-plane
      optical anisotropy induced birefringence that also enabled efficient
      determination of crystallographic orientation using polarized microscopy. The
      lattice vibrations were probed by Raman spectroscopy and exhibited significant
      dependence on thickness of crystals exfoliated down to a single layer. Optical
      absorption determined by reflectance contrast was dominated by d-d-type
      transitions localized at Cr3+ ions, which was also responsible for the major
      photoluminescence peak at 1.31 eV. The spectral features in the absorption and
      emission spectra exhibited noticeable thickness dependence and hinted at a high
      photochemical activity for single-layer CrPS4. The current structural and optical
      investigation will provide a firm basis for future study and application of this
      kind of atomically thin magnetic semiconductors.

PMID- 29068663
TI  - Portable GMR Handheld Platform for the Detection of Influenza A Virus.
AB  - Influenza A virus (IAV) is a common respiratory pathogen infecting many hosts
      including humans, pigs (swine influenza virus or SIV), and birds (avian influenza
      virus or AIV). Monitoring swine and avian influenza viruses in the wild, farms,
      and live poultry markets is of great significance for human and veterinary public
      health. A portable, sensitive, and quantitative immunoassay device will be of
      high demand especially in the rural and resource-limited areas. We report herein
      our Z-Lab point-of-care (POC) device for sensitive and specific detection of
      swine influenza viruses with minimum sample handling and laboratory skill
      requirements. In the present study, a portable and quantitative immunoassay
      platform based on giant magnetoresistive (GMR) technology is used for the
      detection of IAV nucleoprotein (NP) and purified H3N2v. Z-Lab displays
      quantitative results in less than 10 min with sensitivities down to 15 ng/mL and
      125 TCID50/mL for IAV nucleoprotein and purified H3N2v, respectively. This
      platform allows lab-testing to be performed outdoors and opens up the
      applications of immunoassays in nonclinical settings.

PMID- 29068664
TI  - Application of FT-ICR MS Equipped with Quadrupole Detection for Analysis of Crude
      Oil.
AB  - Resolving power is a critical factor determining the quality of ultrahigh
      resolving power mass spectra of crude oil. In this study, 7T Fourier-transform
      ion cyclotron mass spectrometry (FT-ICR MS), equipped with quadrupole detection,
      was applied and evaluated for crude oil analysis for the first time. Four spectra
      were obtained from two oil samples using two ionization methods. Resolving power
      of 1500000 was observed at m/z 400 with 4 s transient signal. Comparison with
      literature reports revealed that the achieved resolving power was comparable with
      or superior to those obtained from instruments using higher magnetic fields but
      without quadrupole detection. A total of 6000-10000 peaks with an S/N ratio of 3
      or higher were observed from the obtained spectra and over 97% of the peaks could
      be assigned to appropriate chemical formulas with an error within 1 ppm. Double
      bond equivalents vs carbon number plots generated from the obtained data agreed
      well with those previously reported without quadrupole detection. Mass accuracy
      values of the assigned elemental formulas were examined and the average root-mean
      square error was calculated to be only 160 ppb. Low unassignment rate of the
      observed peaks and strong agreement with previously reported results suggests
      that unwanted harmonics of reduced frequency are not significant for the data
      obtained with quadrupole detection. Overall, the data presented in this study
      show that FT-ICR MS equipped with quadrupole detection can be a powerful tool to
      examine complex mixtures like crude oil. To the best of our knowledge, this is
      the first paper reporting application of FT-ICR MS equipped with quadrupole
      detection for the oil analysis.

PMID- 29068665
TI  - Enzymatic Installation of Functional Molecules on Amyloid-Based Polymers.
AB  - We produced a functional polymer whose framework comprised transthyretin (TTR)
      amyloid fibrils. In order to immobilize functional molecules onto the amyloid
      fibrils, transpeptidase sortase A (srtA), which catalyzes the covalent binding of
      LPXTG with polyglycine, was employed. After the preparation of the amyloid fibril
      of LPETGG-tagged TTR, immobilization of Gly5-fused GFP on the amyloid fibrils by
      srtA-mediated transpeptidation was carried out. SrtA recognized the amyloid
      fibrils consisting of an LPETGG-tagged TTR variant (L55P) as a good substrate,
      resulting in successful preparation of a GFP-immobilized amyloid. Intriguingly,
      the replacement of GFP with Gly5-fused luciferase was confirmed when the GFP
      immobilized amyloids were mixed with Gly5-luciferase in the presence of srtA.
      Thus, it was found that functional molecules covalently immobilized on amyloid
      could be detached and substituted with other tagged molecules by using srtA.

PMID- 29068666
TI  - Synthesis of Z- or E-Trisubstituted Allylic Alcohols and Ethers by Kinetically
      Controlled Cross-Metathesis with a Ru Catechothiolate Complex.
AB  - The first examples of kinetically controlled cross-metathesis reactions that
      generate Z- or E-trisubstituted alkenes are disclosed. Transformations are
      catalyzed by <=6.0 mol % of a Ru catechothiolate complex and afford
      trisubstituted allylic alcohols and ethers in up to 81% yield and >98%
      stereoisomeric purity. The method has considerable scope, as olefins containing
      an alcohol, an aldehyde, an epoxide, a carboxylic acid, or an alkenyl group may
      be used. Mechanistic models that account for the observed levels and trends in
      efficiency and stereochemical control are provided, based on DFT studies.

PMID- 29068667
TI  - High Nuclearity Assemblies and One-Dimensional (1D) Coordination Polymers Based
      on Lanthanide-Copper 15-Metallacrown-5 Complexes (LnIII = Pr, Nd, Sm, Eu).
AB  - Complexes {[LnCu5(GlyHA)5(m-bdc)(H2O)4-x]2[LnCu5(GlyHA)5(SO4)(m-bdc)(H2O)4]2}.(30
      + 2x)H2O (where GlyHA2- = glycinehydroxamate, m-bdc2- = m-phthalate; Ln = Pr and
      x = 0.21 for compound 1, or Ln = Sm and x = 0.24 for 3) and one-dimensional (1D)
      coordination polymers {[NdCu5(GlyHA)5(H2O)5(m-bdc)]nn[NdCu5(GlyHA)5(H2O)4(MU
      CO3)(m-bdc)]}.13nH2O (2) and {[EuCu5(GlyHA)5(H2O)3](m-bdc)2[EuCu5(GlyHA)5(m
      bdc)(H2O)3]}n.17nH2O (4) were obtained starting from the 15-metallacrown-5
      complexes {[LnCu5(GlyHA)5(SO4)(H2O)6.5]}2(SO4).6H2O (Ln = Pr, Nd, Sm, Eu) by the
      partial or complete metathesis of sulfate anions with m-phthalate. Compounds 1
      and 3 contain unprecedented quadruple-decker neutral metallacrown assemblies,
      where the [LnCu5(GlyHA)5]3+ cations are linked by m-phthalate dianions. In
      contrast, in complexes 2 and 4, these components assemble into 1D chains of
      coordination polymers, the adjacent {[NdCu5(GlyHA)5(H2O)5(m-bdc)]+}n 1D chains in
      2 being separated by discrete [NdCu5(GlyHA)5(H2O)4(MU-CO3)(m-bdc)]}- complex
      anions. The crystal lattices of 2 and 4 contain voids filled by solvent
      molecules. Desolvated 4 is able to absorb up to 0.12 cm3/g of methanol vapor or
      0.04 cm3/g of ethanol at 293 K. The isotherm for methanol absorption by compound
      4 is consistent with a possible "gate opening" mechanism upon interaction with
      this substrate. The chiMT vs T data for complexes 1-4 and their simpler starting
      materials {[LnCu5(GlyHA)5(SO4)(H2O)6.5]}2(SO4).6H2O (Ln(III) = Pr, Nd, Sm, Eu)
      were fitted using an additive model, which takes into account exchange
      interactions between lanthanide(III) and copper(II) ions in the
      metallamacrocycles via a molecular field model. The exchange interactions between
      adjacent Cu(II) ions in metallacrown fragments were found to fall in the range of
      -47 < JCu-Cu < -63 cm-1. These complexes are the first examples of a Ln(III)
      Cu(II) 15-metallacrowns-5 (Ln(III) = Pr, Nd, Sm, Eu), for which values of
      exchange parameters have now been reported.

PMID- 29068668
TI  - Promoted Hydride/Oxide Exchange in SrTiO3 by Introduction of Anion Vacancy via
      Aliovalent Cation Substitution.
AB  - We investigated topochemical anion exchange reactions for a ScIII-substituted
      SrTiIVO3 perovskite, Sr(Ti1-yScy)O3-y/2?y/2 (y <= 0.1), using CaH2. It was found
      that the initial introduction of a small amount of anion vacancies (y/2) is
      crucial to enhance the anion (H-/O2-) exchangeability. For example, hydride
      reduction of Sr(Ti0.95Sc0.05)O2.975 yielded the oxyhydride
      SrTi0.95Sc0.05O2.56H0.41 in which the hydride concentration is increased by 33%
      with respect to pristine SrTiO3 (leading to SrTiO2.76H0.24). This observation
      highlights the importance of anion vacancies to improve anion (H-/O2-) diffusion,
      which is a well-known strategy for improving oxide anion conductivity, and
      suggests that such a vacancy-assisted reaction could be applied to other anion
      exchange reactions (e.g., F-/O2- and N3-/O2-) to extend the solubility range.

PMID- 29068669
TI  - Electrophilic-Nucleophilic Dualism of Nickel(II) toward Ni...I Noncovalent
      Interactions: Semicoordination of Iodine Centers via Electron Belt and Halogen
      Bonding via sigma-Hole.
AB  - The nitrosoguanidinate complex [Ni{NH?C(NMe2)NN(O)}2] (1) was cocrystallized with
      I2 and sym-trifluorotriiodobenzene (FIB) to give associates 1.2I2 and 1.2FIB.
      Structures of these solid species were studied by XRD followed by topological
      analysis of the electron density distribution within the framework of Bader's
      approach (QTAIM) at the M06/DZP-DKH level of theory and Hirshfeld surface
      analysis. Our results along with inspection of XRD (CCDC) data, accompanied by
      the theoretical calculations, allowed the identification of three types of Ni...I
      contacts. The Ni...I semicoordination of the electrophilic nickel(II) center with
      electron belt of I2 was observed in 1.2I2, the metal-involving halogen bonding
      between the nucleophilic nickel(II)-dz2 center and sigma-hole of iodine center
      was recognized and confirmed theoretically in the structure of
      [FeNi(CN)4(IPz)(H2O)]n (IPz = 4-N-coordinated 2-I-pyrazine), whereas the
      arrangement of FIB in 1.2FIB provides a boundary case between the
      semicoordination and the halogen Ni...I bondings. In 1.2I2 and 1.2FIB,
      noncovalent interactions were studied by variable temperature XRD detecting the
      expansion of noncovalent contacts with preservation of covalent bond lengths upon
      the temperature increase from 100 to 300 K. The nature and energies of all
      identified types of the Ni...I noncovalent interactions in the obtained (1.2I2
      and 1.2FIB) and in the previously reported ([FeNi(CN)4(IPz)(H2O)]n,
      [NiL2](I3)2.2I2 (L = o-phenylene-bis(dimethylphosphine), [NiL]I2 (L = 1,4,8,11
      tetra-azacyclotetradecane), Ni(en)2]n[AgI2]2n (en = ethylenediamine), and
      [NiL](ClO4) (L = 4-iodo-2-((2-(2-(2-pyridyl)ethylsulfanyl)ethylimino)methyl)
      phenolate)) structures were studied theoretically. The estimated strengths of
      these Ni...I noncovalent contacts vary from 1.6 to 4.1 kcal/mol and, as expected,
      become weaker on heating. This work is the first emphasizing electrophilic
      nucleophilic dualism of any metal center toward noncovalent interactions.

PMID- 29068670
TI  - Photochemistry and Photophysics in Silica-Based Materials: Ultrafast and Single
      Molecule Spectroscopy Observation.
AB  - Silica-based materials (SBMs) are widely used in catalysis, photonics, and drug
      delivery. Their pores and cavities act as hosts of diverse guests ranging from
      classical dyes to drugs and quantum dots, allowing changes in the photochemical
      behavior of the confined guests. The heterogeneity of the guest populations as
      well as the confinement provided by these hosts affect the behavior of the formed
      hybrid materials. As a consequence, the observed reaction dynamics becomes
      significantly different and complex. Studying their photobehavior requires
      advanced laser-based spectroscopy and microscopy techniques as well as
      computational methods. Thanks to the development of ultrafast (spectroscopy and
      imaging) tools, we are witnessing an increasing interest of the scientific
      community to explore the intimate photobehavior of these composites. Here, we
      review the recent theoretical and ultrafast experimental studies of their
      photodynamics and discuss the results in comparison to those in homogeneous
      media. The discussion of the confined dynamics includes solvation and intra- and
      intermolecular proton-, electron-, and energy transfer events of the guest within
      the SBMs. Several examples of applications in photocatalysis, (photo)sensors,
      photonics, photovoltaics, and drug delivery demonstrate the vast potential of the
      SBMs in modern science and technology.

PMID- 29068671
TI  - Olivine FePO4 Cathode Material for Rechargeable Mg-Ion Batteries.
AB  - In this work, MgxFePO4 is exploited as a cathode material for rechargeable Mg-ion
      batteries. FePO4/C prepared via electrochemical delithiation of LiFePO4/C is
      directly used as the cathode in aqueous Mg2+ electrolyte, and reversible capacity
      is achieved for the first time. Notably, the capacity (82 mA h/g) is half of the
      theoretical value (164 mA h/g) and "asymmetric" discharge/charge behavior can be
      observed. In addition, first-principles calculations show it is the strong Mg-ion
      interactions between adjacent channels that not only limit the capacity of the
      cathode but also lead to the difference in rates for Mg-ion intercalation and
      deintercalation. This work provides experimental and theoretical evidence that
      reveal the mechanism of Mg-ion intercalation and deintercalation in a FePO4 host,
      which gives guidance in designing cathode materials for rechargeable batteries
      based on multivalent metal ions.

PMID- 29068672
TI  - Effects of Black Raspberry Extract and Berry Compounds on Repair of DNA Damage
      and Mutagenesis Induced by Chemical and Physical Agents in Human Oral Leukoplakia
      and Rat Oral Fibroblasts.
AB  - Black raspberries (BRB) have been shown to inhibit carcinogenesis in a number of
      systems, with most studies focusing on progression. Previously we reported that
      an anthocyanin-enriched black raspberry extract (BE) enhanced repair of dibenzo
      [a,l]-pyrene dihydrodiol (DBP-diol)-induced DNA adducts and inhibited DBP-diol
      and DBP-diolepoxide (DBPDE)-induced mutagenesis in a lacI rat oral fibroblast
      cell line, suggesting a role for BRB in the inhibition of initiation of
      carcinogenesis. Here we extend this work to protection by BE against DNA adduct
      formation induced by dibenzo-[a,l]-pyrene (DBP) in a human oral leukoplakia cell
      line (MSK) and to a second carcinogen, UV light. Treatment of MSK cells with DBP
      and DBPDE led to a dose-dependent increase in DBP-DNA adducts. Treatment of MSK
      cells with BE after addition of DBP reduced levels of adducts relative to cells
      treated with DBP alone, and treatment of rat oral fibroblasts with BE after
      addition of DBPDE inhibited mutagenesis. These observations showed that BE
      affected repair of DNA adducts and not metabolism of DBP. As a proof of principle
      we also tested aglycones of two anthocyanins commonly found in berries,
      delphinidin chloride and pelargonidin chloride. Delphinidin chloride reduced DBP
      DNA adduct levels in MSK cells, while PGA did not. These results suggested that
      certain anthocyanins can enhance repair of bulky DNA adducts. As DBP and its
      metabolites induced formation of bulky DNA adducts, we investigated the effects
      of BE on genotoxic effects of a second carcinogen that induces bulky DNA damage,
      UV light. UV irradiation produced a dose-dependent increase in
      cyclobutanepyrimidine dimer levels in MSK cells, and post-UV treatment with BE
      resulted in lower cyclobutanepyrimidine dimer levels. Post-UV treatment of the
      rat lacI cells with BE reduced UV-induced mutagenesis. Taken together, the
      results demonstrate that BE extract reduces bulky DNA damage and mutagenesis and
      support a role for BRB in the inhibition of initiation of carcinogenesis.

PMID- 29068673
TI  - Immobilization of beta-Cyclodextrin-Conjugated Lactoferrin onto Polymer Monolith
      for Enrichment of Ga in Metabolic Residues of Ga-Based Anticancer Drugs.
AB  - Biological-material-functionalized porous monoliths were prepared with
      lactoferrin and beta-cyclodextrin via a click reaction. With the monolith as an
      extraction medium, a method combined with ICP-MS was developed for the
      determination of total gallium originating from metabolic residues of orally
      bioavailable gallium complexes with tris(8-quinolinolato)gallium (GaQ3) as a
      representative. The method exhibited favorable adsorption behaviors for gallium
      with high selectivity, low detection limit (2 ng L-1), and an enrichment factor
      of 29-fold with the sample throughput of 30 min-1. The developed approach was
      validated by the analysis of gallium from GaQ3 metabolic residues in a human cell
      line. Additionally, the practical applicability of this method was evaluated by
      the determination of gallium in human blood and urine samples from cancer
      patients. Results illustrated that the prepared monolith had potential in Ga
      based anticancer drug analysis in complex biological samples.

PMID- 29068674
TI  - Starch Aerogels: A Member of the Family of Thermal Superinsulating Materials.
AB  - Starch aerogels were prepared via dissolution in water (thermomechanical
      treatment), retrogradation, solvent exchange, and drying with supercritical CO2.
      Amylose content in starches was varied from 0 to 100%. The aerogels' bulk
      density, morphology, specific surface area, thermal conductivity, and mechanical
      properties under compression were investigated. Pea starch aerogels had one of
      the highest specific surface area and lowest density and thermal conductivity
      (0.021-0.023 W/m.K), with the latter indicating that a new thermal
      superinsulation material was obtained. A detailed study of the influence of
      processing parameters on pea starch aerogels properties showed the importance of
      retrogradation time which decreases specific surface area and increases
      mechanical properties and thermal conductivity. Finally, a comparison of starch
      aerogel thermal conductivity with that of other bioaerogels is performed.

PMID- 29068675
TI  - Use of Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry and
      Metabonomic Profiling To Differentiate between Normally Slaughtered and Dead on
      Arrival Poultry Meat.
AB  - Metabonomic profiling techniques, with established quality control methods, have
      been used to detect subtle metabolic differences in tissue that could aid in the
      discovery of fraud within the food industry. Liquid chromatography quadrupole
      time-of-flight mass spectrometry (LC-Q-TOF-MS) was utilized to acquire metabolic
      profiles of muscle, heart, and liver tissue from normally slaughtered and dead on
      arrival chickens. A workflow including XCMS Online for data processing and robust
      confirmatory statistics was used in order to differentiate between the two sample
      types. It was found that normally slaughtered and dead on arrival chicken can be
      differentiated based on the metabolic profile and multivariate analysis. Markers
      were found to be significantly different between the two sample types in all
      samples. With the use of the METLIN database and MS/MS analysis of chemical
      standards, sphingosine was identified as a marker in the muscle tissue samples
      which may offer potential for the detection of fraudulently processed chicken
      meat. The approach taken in this work has shown that it is possible to apply the
      described workflows to food fraud problems, with an objective of identifying key
      markers that could be investigated further to determine their usefulness for
      fraud detection.

PMID- 29068676
TI  - Cell-Surface Receptor-Ligand Interaction Analysis with Homogeneous Time-Resolved
      FRET and Metabolic Glycan Engineering: Application to Transmembrane and GPI
      Anchored Receptors.
AB  - Ligand-binding assays are the linchpin of drug discovery and medicinal chemistry.
      Cell-surface receptors and their ligands have traditionally been characterized by
      radioligand-binding assays, which have low temporal and spatial resolution and
      entail safety risks. Here, we report a powerful alternative (GlycoFRET), where
      terbium-labeled fluorescent reporters are irreversibly attached to receptors by
      metabolic glycan engineering. For the first time, we show time-resolved
      fluorescence resonance energy transfer between receptor glycans and fluorescently
      labeled ligands. We describe GlycoFRET for a GPI-anchored receptor, a G-protein
      coupled receptor, and a heterodimeric cytokine receptor in living cells with
      excellent sensitivity and high signal-to-background ratios. In contrast to
      previously described methods, GlycoFRET does not require genetic engineering or
      antibodies to label receptors. Given that all cell-surface receptors are
      glycosylated, we expect that GlycoFRET can be generalized with applications in
      chemical biology and biotechnology, such as target engagement, receptor
      pharmacology, and high-throughput screening.

PMID- 29068677
TI  - Cation Radical Accelerated Nucleophilic Aromatic Substitution via Organic
      Photoredox Catalysis.
AB  - Nucleophilic aromatic substitution (SNAr) is a direct method for arene
      functionalization; however, it can be hampered by low reactivity of arene
      substrates and their availability. Herein we describe a cation radical
      accelerated nucleophilic aromatic substitution using methoxy- and benzyloxy
      groups as nucleofuges. In particular, lignin-derived aromatics containing
      guaiacol and veratrole motifs were competent substrates for functionalization. We
      also demonstrate an example of site-selective substitutive oxygenation with
      trifluoroethanol to afford the desired trifluoromethylaryl ether.

PMID- 29068678
TI  - Efficient and Accurate Born-Oppenheimer Molecular Dynamics for Large Molecular
      Systems.
AB  - An efficient scheme for the calculation of Born-Oppenheimer molecular dynamics
      (BOMD) simulations is introduced. It combines the corrected small basis set
      Hartree-Fock (HF-3c) method by Sure and Grimme [J. Comput. Chem. 2013, 43, 1672],
      extended Lagrangian BOMD (XL-BOMD) by Niklasson et al. [J. Chem. Phys. 2009, 130,
      214109], and the calculation of the two electron integrals on graphics processing
      units (GPUs) [J. Chem. Phys. 2013, 138, 134114; J. Chem. Theory Comput. 2015, 11,
      918]. To explore the parallel performance of our strong scaling implementation of
      the method, we present timings and extract, as its validation and first
      illustrative application, high-quality vibrational spectra from simulated
      trajectories of beta-carotene, paclitaxel, and liquid water (up to 500 atoms). We
      conclude that the presented BOMD scheme may be used as a cost-efficient and
      reliable tool for computing vibrational spectra and thermodynamics of large
      molecular systems including explicit solvent molecules containing 500 atoms and
      more. Simulating 50 ps of maitotoxin (nearly 500 atoms) employing time steps of
      0.5 fs requires ~3 weeks on 12 CPUs (Intel Xeon E5 2620 v3) with 24 GPUs (AMD
      FirePro 3D W8100).

PMID- 29068679
TI  - Understanding a Hydroformylation Catalyst that Produces Branched Aldehydes from
      Alkyl Alkenes.
AB  - This paper reports experimental and computational studies on the mechanism of a
      rhodium-catalyzed hydroformylation that is selective for branched aldehyde
      products from unbiased alkene substrates. This highly unusual selectivity relies
      on a phospholane-phosphite ligand prosaically called BOBPHOS. Kinetic studies
      using in situ high pressure IR (HPIR) and the reaction progress kinetic analysis
      methodology suggested two steps in the catalytic cycle were involved as turnover
      determining. Negative order in CO and positive orders in alkene and H2 were found
      and the effect of hydrogen and carbon monoxide partial pressures on selectivity
      were measured. Labeling studies found rhodium hydride addition to the alkene to
      be largely irreversible. Detailed spectroscopic HPIR and NMR characterization of
      activated rhodium-hydrido dicarbonyl species were carried out. In the absence of
      H2, reaction of the rhodium-hydrido dicarbonyl with allylbenzene allowed further
      detailed spectroscopic characterization of four- and five-coordinate rhodium-acyl
      species. Under single-turnover conditions, the ratios of branched to linear acyl
      species were preserved in the final ratios of aldehyde products. Theoretical
      investigations uncovered unexpected stabilizing CH-pi interactions between the
      ligand and substrate which influenced the high branched selectivity by causing
      potentially low energy pathways to become unproductive. Energy span and degree of
      TOF control analysis strongly support experimental observations and mechanistic
      rationale. A three-dimensional quadrant model was built to represent the
      structural origins of regio- and enantioselectivity.

PMID- 29068680
TI  - Segregation Phenomena in Size-Selected Bimetallic CuNi Nanoparticle Catalysts.
AB  - Surface segregation, restructuring, and sintering phenomena in size-selected
      copper-nickel nanoparticles (NPs) supported on silicon dioxide substrates were
      systematically investigated as a function of temperature, chemical state, and
      reactive gas environment. Using near-ambient pressure (NAP-XPS) and ultrahigh
      vacuum X-ray photoelectron spectroscopy (XPS), we showed that nickel tends to
      segregate to the surface of the NPs at elevated temperatures in oxygen- or
      hydrogen-containing atmospheres. It was found that the NP pretreatment, gaseous
      environment, and oxide formation free energy are the main driving forces of the
      restructuring and segregation trends observed, overshadowing the role of the
      surface free energy. The depth profile of the elemental composition of the
      particles was determined under operando CO2 hydrogenation conditions by varying
      the energy of the X-ray beam. The temperature dependence of the chemical state of
      the two metals was systematically studied, revealing the high stability of nickel
      oxides on the NPs and the important role of high valence oxidation states in the
      segregation behavior. Atomic force microscopy (AFM) studies revealed a remarkable
      stability of the NPs against sintering at temperatures as high as 700  degrees C.
      The results provide new insights into the complex interplay of the various
      factors which affect alloy formation and segregation phenomena in bimetallic NP
      systems, often in ways different from those previously known for their bulk
      counterparts. This leads to new routes for tuning the surface composition of
      nanocatalysts, for example, through plasma and annealing pretreatments.

PMID- 29068681
TI  - Activating MoS2 for pH-Universal Hydrogen Evolution Catalysis.
AB  - MoS2 presents a promising catalyst for the hydrogen evolution reaction (HER) in
      water splitting, but its worse catalytic performance in neutral and alkaline
      media than in acidic environment may be problematic for practical application.
      This is because the other half reaction of water splitting, i.e., oxygen
      evolution reaction, often needs to be implemented in alkaline environment. Here
      we demonstrate a universal strategy that may be used to significantly improve the
      HER catalysis of MoS2 in all kinds of environments from acidic to alkaline,
      proton intercalation. Protons may be enabled to intercalate between monolayer
      MoS2 and underlying substrates or in the interlayer space of thicker MoS2 by two
      processes: electrochemically polarizing MoS2 at negative potentials (vs RHE) in
      acidic media or immersing MoS2 into certain acid solutions like TFSI. The
      improvement in catalytic performance is due to the activity enhancement of the
      active sites in MoS2 by the intercalated protons, which might be related with the
      effect of the intercalated protons on electrical conductance and the adsorption
      energy of hydrogen atoms. The enhancement in catalytic activity by the
      intercalated proton is very stable even in neutral and alkaline electrolytes.

PMID- 29068683
TI  - Perrhenate-Catalyzed Deoxydehydration of a Vicinal Diol: A Comparative Density
      Functional Theory Study.
AB  - Oxo-rhenium compounds, such as perrhenate salts, have demonstrated preferable
      activity in catalyzing the deoxydehydration (DODH) reaction in the presence of
      reductants. Here, the first computational details of the reported DODH mechanisms
      are presented using the density functional theory (DFT) (M06/6
      311+G(d,p)/LANL2DZ) to investigate the conversion of a vicinal diol into the
      corresponding alkene by ReO4- as a catalyst. The DFT studies were carried out to
      evaluate the DODH mechanisms, from the energy point of view, for the conversion
      of phenyl-1,2-ethanediol to styrene by perrhenate anion in the presence of PPh3
      as a reductant through a detailed comparison of two potential pathways including
      pathway A and pathway B. Pathway A includes the sequence of condensation of oxo
      Re(VII) with diol before the reduction of Re(VII) to Re(V), whereas pathway B
      involves the reduction of oxo-Re(VII) to oxo-Re(V) before the condensation
      process. In pathway B, two basic routes (B1 and B2) are possible, which can take
      place through different reaction steps, including the extrusion of alkene from
      Re(V)-diolate in route B1, and the second reduction of the Re(V)-diolate by
      reductant and then the extrusion of alkene from the Re(III)-diolate intermediate
      in route B2. The intermediates and the Gibbs free energy changes, including
      DeltaG degrees g and DeltaG degrees sol, have been calculated for alternative
      pathways (A and B) in the gas and solvent (chlorobenzene and methanol) phases and
      compared to each other. In addition, the transition states and the activation
      energy barriers for two pathways (A and B) in the gas phase and in chlorobenzene
      have been calculated. The key transition states include the nucleophilic attack
      of PPh3 on an Re?O bond, the dissociation of OPPh3 from the rhenium moiety, the
      transfer of an H atom of diol to the oxo ligand in an oxo-Re bond through the
      condensation step, and the extrusion of styrene from the Re-diolate complexes.
      The DFT results indicate that the DODH reaction is thermodynamically feasible
      through both pathways (A and B). However, the calculations reveal that the
      perrhenate-catalyzed DODH reaction through pathway A has the lowest overall
      activation barrier energy among the DODH mechanism routes.

PMID- 29068682
TI  - Activity-Based Probes for Isoenzyme- and Site-Specific Functional
      Characterization of Glutathione S-Transferases.
AB  - Glutathione S-transferases (GSTs) comprise a diverse family of phase II drug
      metabolizing enzymes whose shared function is the conjugation of reduced
      glutathione (GSH) to endo- and xenobiotics. Although the conglomerate activity of
      these enzymes can be measured, the isoform-specific contribution to the
      metabolism of xenobiotics in complex biological samples has not been possible. We
      have developed two activity-based probes (ABPs) that characterize active GSTs in
      mammalian tissues. The GST active site is composed of a GSH binding "G site" and
      a substrate binding "H site". Therefore, we developed (1) a GSH-based
      photoaffinity probe (GSTABP-G) to target the "G site", and (2) an ABP designed to
      mimic a substrate molecule and have "H site" activity (GSTABP-H). The GSTABP-G
      features a photoreactive moiety for UV-induced covalent binding to GSTs and GSH
      binding enzymes. The GSTABP-H is a derivative of a known mechanism-based GST
      inhibitor that binds within the active site and inhibits GST activity. Validation
      of probe targets and "G" and "H" site specificity was carried out using a series
      of competition experiments in the liver. Herein, we present robust tools for the
      characterization of enzyme- and active site-specific GST activity in mammalian
      model systems.

PMID- 29068684
TI  - Absorption and Fluorescence Features of an Amphiphilic meso-Pyrimidinylcorrole:
      Experimental Study and Quantum Chemical Calculations.
AB  - Corroles are emerging as an important class of macrocycles with numerous
      applications because of their peculiar photophysical and metal chelating
      properties. meso-Pyrimidinylcorroles are easily deprotonated in certain solvents,
      which changes their absorption and emission spectra as well as their accessible
      supramolecular structures. To enable control over the formation of supramolecular
      structures, the dominant corrole species, i.e., the deprotonated form or one of
      the two NH-tautomers, needs to be identified. Therefore, we focus in the present
      article on the determination of the UV-vis spectroscopic properties of the free
      base NH-tautomers and the deprotonated form of a new amphiphilic meso
      pyrimidinylcorrole that can assemble to supramolecular structures at
      heterointerfaces as utilized in the Langmuir-Blodgett and liquid-liquid interface
      precipitation techniques. After quantification of the polarities of the free-base
      NH-tautomers and the deprotonated form by means of quantum chemically derived
      electrostatic potential distributions at the corroles' van der Waals surfaces,
      the preferential stabilization of (some of) the considered species in solvents of
      different polarity is identified by means of absorption spectroscopy. For the
      solutions with complex mixtures of species, we applied fluorescence excitation
      spectroscopy to estimate the relative weights of the individual corrole species.
      This technique might also be applied to identify dominating species in
      molecularly thin films directly on the subphase' surface of Langmuir-Blodgett
      troughs. Supported by quantum chemical calculations we were able to differentiate
      between the spectral signatures of the individual NH-tautomers by means of
      fluorescence excitation spectroscopy.

PMID- 29068685
TI  - Development of Monoclonal Antibodies Recognizing Linear Epitope: Illustration by
      Three Bacillus thuringiensis Crystal Proteins of Genetically Modified Cotton,
      Maize, and Tobacco.
AB  - Bacillus thuringiensis Cry1Ac, Cry1Ia1, and Cry1Ie are delta-endotoxin
      insecticidal proteins widely implemented in genetically modified organisms (GMO),
      such as cotton, maize, and potato. Western blot assay integrates electrophoresis
      separation power and antibody high specificity for monitoring specific exogenous
      proteins expressed in GMO. Procedures for evoking monoclonal antibody (mAb) for
      Western blot were poorly documented. In the present study, Cry1Ac partially
      denatured at 100  degrees C for 5 min was used as an immunogen to develop mAbs
      selectively recognizing a linear epitope of Cry1Ac for Western blot. mAb 5E9C6
      and 3E6E2 selected with sandwich ELISA strongly recognized the heat semidenatured
      Cry1Ac. Particularly, 3E6E2 recognized both E. coli and cotton seed expressed
      Cry1Ac in Western blot. Such strategy of using partially denatured proteins as
      immunogens and using sandwich ELISA for mAb screening was also successfully
      demonstrated with production of mAbs against Cry1Ie for Western blot assay in
      maize.

PMID- 29068686
TI  - Multimycotoxin LC-MS/MS Analysis in Tea Beverages after Dispersive Liquid-Liquid
      Microextraction (DLLME).
AB  - The aim of the present study was to develop a multimycotoxin liquid
      chromatography tandem mass spectrometry (LC-MS/MS) method with a dispersive
      liquid-liquid microextraction procedure (DLLME) for the analysis of AFs, 3aDON,
      15aDON, NIV, HT-2, T-2, ZEA, OTA, ENNs, and BEA in tea beverages and to evaluate
      their mycotoxin contents. The proposed method was characterized in terms of
      linearity, limits of detection (LODs), limits of quantification (LOQs),
      recoveries, repeatability (intraday precision), reproducibility (interday
      precision), and matrix effects to check suitability. The results show LODs in the
      range of 0.05-10 MUg/L, LOQs in the range of 0.2-33 MUg/L, and recoveries in the
      range of 65-127% (RSD < 20%). The method developed in this study was applied to
      44 commercial samples of black tea, red tea, green tea, and green mint tea. The
      results show that, of the analyzed mycotoxins, AFB2, AFG2, 15aDON, AFG1, and ENB
      were detected in the samples. AFB2 (14.4-32.2 MUg/L) and 15aDON (60.5-61 MUg/L)
      presented the highest levels. Green mint tea contained the highest concentration
      of mycotoxins. The risk assessment study shows that the population is not much
      exposed to mycotoxins through the consumption of tea beverages.

PMID- 29068687
TI  - Chasing Weak Forces: Hierarchically Assembled Helicates as a Probe for the
      Evaluation of the Energetics of Weak Interactions.
AB  - London dispersion forces are the weakest interactions between molecules. Because
      of this, their influence on chemical processes is often low, but can definitely
      not be ignored, and even becomes important in cases of molecules with large
      contact surfaces. Hierarchically assembled dinuclear titanium(IV) helicates
      represent a rare example in which the direct observation of London dispersion
      forces is possible in solution even in the presence of strong cohesive solvent
      effects. Hereby, the dispersion forces do not unlimitedly support the formation
      of the dimeric complexes. Although they have some favorable enthalpic
      contribution to the dimerization of the monomeric complex units, large flexible
      substituents become conformationally restricted by the interactions leading to an
      entropic disadvantage. The dimeric helicates are entropically destabilized.

PMID- 29068689
TI  - Huge Trionic Effects in Graphene Nanoribbons.
AB  - One- and two-dimensional materials are being intensively investigated due to
      their interesting properties for next-generation optoelectronic devices. Among
      these, armchair-edged graphene nanoribbons are very promising candidates with
      optical properties that are dominated by excitons. In the presence of additional
      charges, trions (i.e., charged excitons) can occur in the optical spectrum. With
      our recently developed first-principle many-body approach (Phys. Rev. Lett. 116,
      196804), we predict strongly bound trions in free-standing nanoribbons with large
      binding energies of 140-660 meV for widths of 14.6-3.6 A. Both for the trions and
      for the excitons, we observe an almost linear dependency of their binding
      energies on the band gap. We observe several trion states with different
      character derived from the corresponding excitons. Because of the large bindings
      energies, this opens a route to applications by which optical properties are
      easily manipulated, for example, by electrical fields.

PMID- 29068688
TI  - Direct, Mild, and General n-Bu4NBr-Catalyzed Aldehyde Allylsilylation with Allyl
      Chlorides.
AB  - A direct, mild, and general method for the enantioselective allylsilylation of
      aldehydes with allyl chlorides is reported. The reactions are effectively
      catalyzed by 5 mol % of n-Bu4NBr, and this rate acceleration allows the use of
      complex allyl donors in fragment-coupling reactions and of electron-deficient
      allyl donors. The results are (1) significant progress toward a "universal"
      asymmetric aldehyde allylation reaction that can reliably and highly
      stereoselectively couple any allyl chloride_aldehyde combination and (2) the
      discovery of a novel mode of nucleophilic catalysis for aldehyde allylsilylation
      reactions.

PMID- 29068690
TI  - Ecotoxico-Proteomics for Aquatic Environmental Monitoring: First in Situ
      Application of a New Proteomics-Based Multibiomarker Assay Using Caged Amphipods.
AB  - As a proof of principle, a selected reaction monitoring (SRM) mass spectrometry
      based methodology was applied to the simultaneous quantification of dozens of
      protein biomarkers in caged amphipods (Gammarus fossarum). We evaluated the
      suitability of the methodology to assess complex field contaminations through its
      application in the framework of a regional river monitoring network. Thanks to
      the high throughput acquisition of biomarker levels in G. fossarum exposed in
      four reference and 13 contaminated sites, we analyzed the individual responses of
      38 peptides reporting for 25 proteins of interest in 170 organisms. Responses
      obtained in contaminated sites included inductions of vitellogenin-like proteins
      in male organisms, inductions of Na+K+/ATPases, and strong inhibitions of molt
      related proteins such as chitinase and JHE-carboxylesterase. Proteins from
      detoxification and immunity processes were also found modulated in abundance.
      Summarizing, the results presented here show that the SRM strategy developed for
      multibiomarker measurement paves a very promising way to define multiple
      indicators of the health status of sentinel organisms for environmental hazard
      assessment.

PMID- 29068691
TI  - Myocardial Injury Is Distinguished from Stable Angina by a Set of Candidate
      Plasma Biomarkers Identified Using iTRAQ/MRM-Based Approach.
AB  - The lack of precise biomarkers that identify patients at risk for myocardial
      injury and stable angina delays administration of optimal therapy. Hence, the
      search for noninvasive biomarkers that could accurately stratify patients with
      impending heart attack, from patients with stable coronary artery disease (CAD),
      is urgently needed in the clinic. Herein, we performed comparative quantitative
      proteomics on whole plasma sampled from patients with stable angina (NMI), acute
      myocardial infarction (MI), and healthy control subjects (Ctrl). We detected a
      total of 371 proteins with high confidence (FDR < 1%, p < 0.05) including 53
      preliminary biomarkers that displayed >=2-fold modulated expression in patients
      with CAD (27 associated with atherosclerotic stable angina, 26 with myocardial
      injury). In the verification phase, we used label-free LC-MRM-MS-based targeted
      method to verify the preliminary biomarkers in pooled plasma, excluded peptides
      that were poorly distinguished from background, and performed further validation
      of the remaining candidates in 49 individual plasma samples. Using this approach,
      we identified a final panel of eight novel candidate biomarkers that were
      significantly modulated in CAD (p < 0.05) including proteins associated with
      atherosclerotic stable angina that were implicated in endothelial dysfunction
      (F10 and MST1), proteins associated with myocardial injury reportedly involved in
      plaque destabilization (SERPINA3, CPN2, LUM), and in tissue protection/repair
      mechanisms (ORM2, ACTG1, NAGLU). Taken together, our data showed that candidate
      biomarkers with potential diagnostic values can be successfully detected in
      nondepleted human plasma using an iTRAQ/MRM-based discovery-validation approach
      and demonstrated the plausible clinical utility of the proposed panel in
      discriminating atherosclerotic stable angina from myocardial injury in the
      studied cohort.

PMID- 29068692
TI  - Electrically Driven Unidirectional Optical Nanoantennas.
AB  - Directional antennas revolutionized modern day telecommunication by enabling
      precise beaming of radio and microwave signals with minimal loss of energy.
      Similarly, directional optical nanoantennas are expected to pave the way toward
      on-chip wireless communication and information processing. Currently, on-chip
      integration of such antennas is hampered by their multielement design or the
      requirement of complicated excitation schemes. Here, we experimentally
      demonstrate electrical driving of in-plane tunneling nanoantennas to achieve
      broadband unidirectional emission of light. Far-field interference, as a result
      of the spectral overlap between the dipolar emission of the tunnel junction and
      the fundamental quadrupole-like resonance of the nanoantenna, gives rise to a
      directional radiation pattern. By tuning this overlap using the applied voltage,
      we record directivities as high as 5 dB. In addition to electrical tunability, we
      also demonstrate passive tunability of the directivity using the antenna
      geometry. These fully configurable electrically driven nanoantennas provide a
      simple way to direct optical energy on-chip using an extremely small device
      footprint.

PMID- 29068694
TI  - Adherence to CONSORT Items in Randomized Controlled Trials of Integrative
      Medicine for Colorectal Cancer Published in Chinese Journals.
AB  - BACKGROUND: The majority of studies of integrative treatment for colorectal
      cancer (CRC) have been published in Chinese journals. These studies indicate
      potential benefits, but concerns have been raised over the quality of trials
      published in Chinese journals. The CONSORT statement provides a guide for study
      reporting that has been endorsed by more than 400 international journals.
      Previous studies have used the CONSORT checklist to assess the quality of
      randomized controlled trials (RCTs). OBJECTIVES: This study focused on RCTs of
      integrative and traditional medicine for CRC published in Chinese journals and
      assessed: (1) the overall quality of reporting with a focus on methodological
      aspects; (2) change over time; and (3) the influence of study funding, level of
      institution conducting the trial, rank of the journal, and the length of the
      article. DESIGN: Searches of seven databases identified RCTs. Quality was
      assessed using CONSORT 2010 with adaptations to facilitate scoring. Additional
      codes were added for publication year, hospital rank, report length, and status
      of the journal. Scores of each checklist item, total scores, and scores for eight
      items associated with RCT methodology were calculated. RESULTS: Eighty-one
      studies were included in the main analyses. The RCT methodology subgroup scores
      were significantly higher in studies: with public funding, conducted by authors
      from university hospitals, published in higher ranked journals, and in longer
      articles. CONCLUSIONS: Few Chinese journals mention CONSORT in their author
      guidelines. In these RCTs on CRC better reporting of RCT methodology was
      associated with ranking of the journal as "core," public funding of the RCT, and
      first or correspondent author from a university hospital but the quality of
      reporting had not significantly improved in 15 years. As the volume of scientific
      information produced in China grows, it is imperative that there is growth in the
      quality of this information.

PMID- 29068695
TI  - Toward an Emerging Era of Optimization Research for Acupuncture.

PMID- 29068693
TI  - In Vivo Pulmonary Delivery and Magnetic-Targeting of Dry Powder Nano-in
      Microparticles.
AB  - This brief communication evaluates the cytotoxicity and targeting capability of a
      dry powder chemotherapeutic. Nano-in-microparticles (NIMs) are a dry powder drug
      delivery vehicle containing superparamagnetic iron oxide nanoparticles (SPIONs)
      and either doxorubicin (w/w solids) or fluorescent nanospheres (w/v during
      formulation; as a drug surrogate) in a lactose matrix. In vitro cytotoxicity was
      evaluated in A549 adenocarcinoma cells using MTS and LDH assays to assess
      viability and toxicity after 48 h of NIMs exposure. In vivo magnetic-field
      dependent targeting of inhaled NIMs was evaluated in a healthy mouse model. Mice
      were endotracheally administered fluorescently labeled NIMs either as a dry
      powder or a liquid aerosol in the presence of an external magnet placed over the
      left lung. Quantification of fluorescence and iron showed a significant increase
      in both fluorescence intensity and iron content to the left magnetized lung. In
      comparison, we observed decreased targeting of fluorescent nanospheres to the
      left lung from an aerosolized liquid suspension, due to the dissociation of
      SPIONs and nanoparticles during pulmonary administration. We conclude that dry
      powder NIMs maintain the therapeutic cytotoxicity of doxorubicin and can be
      better targeted to specific regions of the lung in the presence of a magnetic
      field, compared to a liquid suspension.

PMID- 29068696
TI  - Usefulness of the University of California San Diego Performance-Based Skills
      Assessment for the evaluation of cognitive function and activities of daily
      living function in patients with cognitive impairment.
AB  - OBJECTIVES: To assess the usefulness of the University of California San Diego
      Performance-Based Skills Assessment (UPSA) as a new diagnostic method and tool
      for the assessment of cognitive function and activities of daily living function
      in patients with cognitive impairment. METHOD: In total, 35 patients with
      cognitive impairment and 35 healthy controls were recruited for this study. The
      Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global
      Deterioration Scale (GDS) were used for the evaluation of cognitive function,
      while the Barthel Activities of Daily Living Index (BADL), Instrumental
      Activities of Daily Living Index (IADL), and UPSA were used for the evaluation of
      activities of daily living function. RESULTS: UPSA scores were significantly
      lower in patients with cognitive impairment than in controls. The UPSA total
      score was significantly correlated with MMSE, CDR, GDS, and IADL scores. With
      regard to the detection of cognitive impairment, UPSA exhibited a greater
      determination power (R2 = 0.593) compared with BADL (R2 = 0.149) and IADL (R2 =
      0.423) and higher sensitivity and specificity compared with IADL. CONCLUSION: Our
      results suggest that UPSA is a useful tool for the evaluation of cognitive
      function and activities of daily living function in patients with cognitive
      impairment.

PMID- 29068697
TI  - Needs and quality of life of people with middle-stage dementia and their family
      carers from the European Actifcare study. When informal care alone may not
      suffice.
AB  - OBJECTIVE: The Actifcare (Access to timely formal care) study investigated needs
      of people with dementia and their families during the phase in which formal care
      is being considered, and examined whether higher need levels are related to lower
      quality of life (QOL). METHOD: From eight European countries 451 people with
      dementia and their carers participated. Needs were measured with the Camberwell
      Assessment of Need for the Elderly. QOL was measured with the QOL-AD, and carer
      quality of life was measured with the CarerQol. The relationship between needs
      and QOL was analysed with multiple regression analyses. RESULTS: Needs were
      expressed in the domains of psychological distress, daytime activities, company
      and information. People with dementia rated their unmet needs significantly lower
      than their carers: the mean number of self-rated unmet needs was 0.95, whereas
      the mean proxy ratings were 1.66. For met needs, the self-rated mean was 5.5 and
      was 8 when proxy-rated. The level of needs reported was negatively associated
      with QOL for both. CONCLUSION: The study results show that informal carers
      reported almost twice as many needs as people with dementia. The domains in which
      needs are expressed should be the primary focus for interventions to support  
      QOL. The perspectives of people with dementia are informative when identifying
      needs.

PMID- 29068699
TI  - Features of Illness Versus Features of Romantic Relationships as Predictors of
      Cognitive and Behavioral Coping Among Individuals with Type 2 Diabetes.
AB  - For individuals with a chronic illness, such as type 2 diabetes, a multitude of
      factors may influence the ways people cope with their condition. This study
      compares characteristics of the illness and characteristics of a patient's
      romantic relationship as factors that predict coping behaviors for individuals
      with type 2 diabetes. Specifically, we identify illness uncertainty as a feature
      of chronic illness, as well as relational uncertainty and interference from
      partners as relationship characteristics that are associated with coping
      behaviors. Using Amazon Mechanical Turk, we recruited 500 participants who were
      diagnosed with type 2 diabetes and involved in a romantic relationship to
      complete an online survey about the ways they manage their illness in the context
      of their relationship. Structural equation model results showed that relational
      uncertainty and partner interference were both positively associated with the
      perceived threat of discussing the illness, whereas the effect for illness
      uncertainty was nonsignificant; thus, relationship characteristics were a more
      robust predictor of perceived threat than illness characteristics. In turn, the
      perceived threat of discussing the illness was negatively associated with
      treatment compliance and positively associated with topic avoidance about the
      illness. Treatment compliance was also negatively associated with topic
      avoidance. Implications for health and relationships are discussed.

PMID- 29068698
TI  - The Impact of Dietary Polyphenols on COX-2 Expression in Colorectal Cancer.
AB  - Polyphenols are natural compounds with high structural diversity whose common
      occurrence in plants renders them intrinsic dietary components. They are known to
      be secondary metabolites characterized by a wide spectrum of biological
      activities, and a growing body of evidence indicates they have anti-inflammatory
      potential. It is well known that inflammation plays a key role in many chronic
      diseases such as circulatory diseases, pulmonary diseases, autoimmune diseases,
      diabetes, cancer, and neurodegenerative diseases. Polyphenols influence the
      inflammatory process by controlling and inhibiting pro-inflammatory cytokines
      such as IL-1beta, IL-6, IL-8, and TNF-alpha, and cyclooxygenase-2 (COX-2) enzyme
      involved in the metabolism of arachidonic acid. Furthermore, polyphenols exhibit
      anti-inflammatory activity on many levels via NF-kappaB inhibition, and MAPK,
      iNOS, and growth factors regulation. This paper reviews the current state of
      knowledge concerning the potential of various dietary polyphenols to inhibit the
      effects of COX-2 in colon cancer, by examining the available evidence regarding
      the efficacy and safety of these compounds obtained from in vitro and animal
      studies.

PMID- 29068701
TI  - Healthcare Providers' Responses to Narrative Communication About Racial
      Healthcare Disparities.
AB  - We used qualitative methods (semi-structured interviews with healthcare
      providers) to explore: 1) the role of narratives as a vehicle for raising
      awareness and engaging providers about the issue of healthcare disparities and 2)
      the extent to which different ways of framing issues of race within narratives
      might lead to message acceptance for providers' whose preexisting beliefs about
      causal attributions might predispose them to resist communication about racial
      healthcare disparities. Individual interviews were conducted with 53 providers
      who had completed a prior survey assessing beliefs about disparities.
      Participants were stratified by the degree to which they believed providers
      contributed to healthcare inequality: low provider attribution (LPA) versus high
      provider attribution (HPA). Each participant read and discussed two differently
      framed narratives about race in healthcare. All participants accepted the
      "Provider Success" narratives, in which interpersonal barriers involving a
      patient of color were successfully resolved by the provider narrator, through
      patient-centered communication. By contrast, "Persistent Racism" narratives, in
      which problems faced by the patient of color were more explicitly linked to
      racism and remained unresolved, were very polarizing, eliciting acceptance from
      HPA participants and resistance from LPA participants. This study provides a
      foundation for and raises questions about how to develop effective narrative
      communication strategies to engage providers in efforts to reduce healthcare
      disparities.

PMID- 29068700
TI  - Silibinin Reduces the Impact of Obesity on Invasive Liver Cancer.
AB  - Obesity is associated with non-alcoholic steatohepatitis (NASH) and
      hepatocellular carcinoma (HCC). Obesity and metabolic abnormalities resulting in
      low-grade inflammation can increase the risk of developing NASH and HCC. NASH, a
      risk factor for HCC, is characterized by increased inflammation, lipid
      accumulation, and liver injury. Obesogenic proteins modulate signaling pathways
      that induce physiological changes including lipogenesis, ROS, and inflammation.
      Silibinin, a polyphenol in milk thistle seed, has been shown to have anti
      inflammatory properties. Studies have yet to determine whether silibinin can be
      used to dissect the obesity-cancer link to delay progression of liver cancer.
      Using an in vitro model, sera from obese (OB), overweight (OW), or normal weight
      (NW) males (based on BMI) were used to determine the efficacy of silibinin to
      reduce the pro-tumorigenic properties of obesity. HepG2 cells were exposed to OB,
      OW, NW +/- silibinin and tested for growth, ROS, lipogenesis, MMP-9, invasion and
      protein expression. Silibinin suppressed obesity-induced growth, ROS,
      lipogenesis, MMP-9, and cell invasion. These physiological changes corresponded
      with decreased FASN, IL-6, IL-1B, and phosphorylated Erk. We describe the
      differential effect of sera from OB, OW, and NW males on characteristics relevant
      for liver cancer and the potential use of silibinin to mitigate these effects.

PMID- 29068702
TI  - Reliability and Concurrent Validity of Select C3 Logix Test Components.
AB  - We sought to investigate the one-week and within-session reliability of the
      instrumented balance error scoring system test and the concurrent validity/one
      week reliability of two neurocognitive assessments available through C3 Logix. (n
      = 37) Participants completed two balance error scoring system tests separated by
      the Trails A, Trails B, and Symbol Digit Modality test available through C3
      Logix, and with paper and pencil. We found that the instrumented balance error
      scoring system test demonstrated strong one-week reliability and that
      neuropsychological tests available through C3 Logix show acceptable concurrent
      validity with standard (comparable) paper and pencil measures.

PMID- 29068703
TI  - Digging for Dementia: Exploring the experience of community gardening from the
      perspectives of people with dementia.
AB  - OBJECTIVES: The study sought to explore the lived experiences of people with
      dementia who participate in community-based gardening programmes. METHODS: A
      collaborative gardening project was conducted over six weeks at a day centre for
      people with dementia. Six participants were recruited from the centre's
      attendees. Each session was co-designed by participants. Semi-structured group
      interviews were conducted each week, and researcher observations were documented.
      Semi-structured interviews were also conducted with the centre's staff to explore
      their views and to contextualise gardening participants' experiences. Data were
      analysed inductively using thematic analysis. This paper focuses upon three of
      the study's emergent themes: identity, agency, and community. RESULTS: The
      findings revealed that for people with dementia, gardening is not merely a matter
      of enjoying time outdoors; it is a forum for the articulation of identity and
      selfhood and expression of agency, and can facilitate the development of new
      social bonds based upon shared interests, rather than a shared diagnosis.
      CONCLUSION: Gardening-based interventions can offer more than simply facilitating
      outdoor engagement and promoting social interaction. When conditions are right,
      gardening can be an effective vehicle for the promotion of social citizenship and
      expression of selfhood and agency in dementia.

PMID- 29068704
TI  - Effects of Enrichment Presentation and Other Factors on Behavioral Welfare of
      Pantropical Spotted Dolphin (Stenella attenuata).
AB  - Environmental enrichment is a crucial element of promoting welfare for animals in
      captivity. However, enrichment programs are not always formally evaluated for
      their efficacy. Furthermore, there is little empirical evidence of enrichment
      evaluation for species of small cetaceans in zoological settings. A wide range of
      variables may potentially influence enrichment efficacy and how it in turn
      affects behavior. The purpose of this study was to determine the most preferred
      environmental enrichment, and method of presentation, for a species that has not
      been well studied in captivity, the pantropical spotted dolphin (Stenella
      attenuata). In order to determine which enrichment items and method of
      presentation were most effective at eliciting enrichment interaction, we
      systematically examined how several variables of enrichment influenced enrichment
      interaction. The results suggested that presenting enrichment after training
      sessions influenced interaction with the enrichment. The results also indicated
      preference for enrichment type and a specific enrichment device. Finally, factors
      that influenced interaction were also found to influence aberrant behavior. The
      results support the premise that enrichment be "redefined" for each species and
      each individual.

PMID- 29068705
TI  - Campaign Preparation for Complex Initiatives: A Person-Centered Approach to
      Audience Segmentation of Parents' Antibiotic Stewardship.
AB  - The evolution of antibiotic resistance is outpacing the speed at which new
      antibiotics will reach the marketplace. To slow the rate of resistance, people
      need to engage in antibiotic stewardship, which includes acts to prevent the
      spread of bacteria and judicious use of antibiotics to treat infections. This
      study identified the patterns and predictors of antibiotic stewardship behaviors
      of parents (N = 516) related to their children. The latent class analysis
      revealed three profiles of parental stewardship, labeled Stewards, Requesters,
      and Non-Stewards. The findings implied different campaign goals: to encourage
      Stewards to follow through on their intentions, to encourage Requesters to stop
      asking providers for antibiotics when their children have ear infections, and to
      influence Non-Stewards to accept medical advice when an antibiotic is not
      indicated and to dispose of leftover antibiotics. The covariate analysis provided
      theoretical insight into the strategies to pursue in campaigns targeting these
      three groups. For example, parents who perceived antibiotic-resistant infections
      as less serious health conditions, felt less worry when thinking about their
      child getting an antibiotic-resistant infection, and had stronger misattributions
      of antibiotics' efficacy to treat multiple symptoms were more likely to be
      Requesters and Non-Stewards, instead of Stewards.

PMID- 29068706
TI  - Genetic and environmental risk factors for developmental dyslexia in children:
      systematic review of the last decade.
AB  - Despite advances in the characterization of developmental dyslexia (DD), several
      questions regarding the interplay between DD-susceptibility genes and
      environmental risk factors remain open. This systematic review aimed at answering
      the following questions: What has been the impact of new resources on the
      knowledge about DD? Which questions remain open? What is the investigative agenda
      for the short term? Forty-six studies were analyzed. Despite the growing
      literature on DD candidate genes, most studies have not been replicated. We found
      large effects on causative genes and smaller environmental contributions,
      involving maternal smoking during pregnancy, SES and the DYX1C1-1259C/G marker.
      Implications are discussed.

PMID- 29068707
TI  - Correlates and Consequences of Worker Polymorphism in Ants.
AB  - Body size is a key life-history trait influencing all aspects of an organism's
      biology. Ants provide an interesting model for examining body-size variation
      because of the high degree of worker polymorphism seen in many taxa. We review
      worker-size variation in ants from the perspective of factors internal and
      external to the colony that may influence body-size distributions. We also
      discuss proximate and ultimate causes of size variation and how variation in
      worker size can promote worker efficiency and colony fitness. Our review focuses
      on two questions: What is our current understanding of factors influencing worker
      size variation? And how does variation in body size benefit the colony? We
      conclude with recommendations for future work aimed at addressing current
      limitations and ask, How can we better understand the contribution of worker body
      size variation to colony success? And, what research is needed to address gaps in
      our knowledge?

PMID- 29068708
TI  - Impact of the Invasive Brown Marmorated Stink Bug in North America and Europe:
      History, Biology, Ecology, and Management.
AB  - The brown marmorated stink bug (BMSB), Halyomorpha halys (Stal), is an invasive
      pentatomid introduced from Asia into the United States, Canada, multiple European
      countries, and Chile. In 2010, BMSB populations in the mid-Atlantic United States
      reached outbreak levels and subsequent feeding severely damaged tree fruit as
      well as other crops. Significant nuisance issues from adults overwintering inside
      homes were common. BMSB is a highly polyphagous species with a strong dispersal
      capacity and high reproductive output, potentially enabling its spread and
      success in invaded regions. A greater understanding of BMSB biology and ecology
      and its natural enemies, the identification of the male-produced aggregation
      pheromone, and the recognition that BMSB disperses into crops from adjacent
      wooded habitats have led to the development of behavior-based integrated pest
      management (IPM) tactics. Much is still unknown about BMSB, and continued long
      term collaborative studies are necessary to refine crop-specific IPM programs and
      enhance biological control across invaded landscapes.

PMID- 29068710
TI  - Efficacy of Combination Treatment with Sodium Metasilicate and Sodium
      Hypochlorite for Inactivation of Norovirus on Fresh Vegetables.
AB  - In recent years, fresh vegetables have frequently been associated with the
      foodborne transmission of enteric viruses, such as human norovirus (NoV).
      Therefore, several studies have focused on developing methods to inactivate
      foodborne viruses for preventing outbreaks of foodborne illnesses. Sodium
      hypochlorite (NaOCl) is commonly used as a disinfectant, but results in
      undesirable effects on the appearance and taste of foods and can generate toxic
      byproducts when it exceeds the allowable concentration. Here, we evaluated the
      efficacy of a range of NaOCl concentrations (50-1000 ppm) for reducing the
      amounts of human NoV (NoV GII.4) on lettuce (Lactuca sativa), celery (Apium
      graveolens L.), and white cabbage (Brassica oleracea ssp. capitata). In addition,
      the combination treatment of NaOCl and sodium metasilicate (SMS, 0.1-0.5%)
      pentahydrate was evaluated for its ability to decrease the populations of NoV
      GII.4 in the three food samples. An immunomagnetic separation procedure combined
      with reverse transcription quantitative polymerase chain reaction was used for
      virus detection. For lettuce, celery, and cabbage, the NoV GII.4 recovery rates
      were 57.3% +/- 6.5%, 52.5% +/- 1.7%, and 60.3% +/- 3.9%, respectively, using a
      glycine/NaCl elution buffer (0.25 M glycine/0.14 M NaCl, pH 9.5). The reductions
      of NoV GII.4 were 3.17, 3.06, and 3.27 log10 genomic copies/MUL for lettuce,
      celery, and cabbage, respectively, at 1000 ppm NaOCl, while a reduction of ~3
      log10 genomic copies/MUL was obtained when the samples were treated with a
      combination of 100 ppm NaOCl and 0.4% SMS pentahydrate. Taken together, these
      results demonstrated that combined treatment with NaOCl and SMS pentahydrate was
      an efficient strategy to reduce the concentration of NaOCl for control of NoV
      GII.4 contamination in fresh vegetables.

PMID- 29068709
TI  - Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During
      Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study.
AB  - BACKGROUND: Enthusiasm for the benefits of sodium-glucose cotransporter 2
      inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been
      offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump
      treated T1D patients are susceptible to DKA due to infusion site problems, this
      study was undertaken to assess how treatment with SGLT2i affects patterns of
      early metabolic decompensation following suspension of basal insulin. METHODS:
      Ten T1D participants (age 19-35 years, duration 10 +/- 8 years, A1c 7.4% +/-
      0.8%) underwent overnight pump suspension studies before and after treatment with
      canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and
      plasma glucose (PG), beta-hydroxybutyrate (BHB), free fatty acids (FFA), plasma
      insulin (PI), and glucagon were measured. Studies were terminated 6 h after
      suspension or if PG rose to >350 mg/dL or BHB >2.5 mmol/L. RESULTS: PI levels at
      the start of suspension were reduced by 30% after CANA treatment (44 +/- 11 uU/mL
      vs. 31 +/- 10 uU/mL, P < 0.01), but baseline PG, BHB, FFA, and glucagon levels
      were not significantly different. During the suspension, PG rose from 104 +/- 10
      to 301 +/- 21 mg/dL before treatment, but only from 109 +/- 8 to 195 +/- 14 mg/dL
      after treatment (P = 0.002 vs. pretreatment values). On the other hand, CANA
      treatment did not significantly affect the magnitude of increases in FFA, BHB,
      and glucagon levels during the suspension study. CONCLUSION: These data indicate
      that SGLT2i do not accelerate the rate of ketogenesis following the interruption
      of basal insulin infusion in T1D. Rather, the failure of patients to promptly
      recognize early metabolic decompensation relates to the much more gradual rise in
      PG levels.

PMID- 29068711
TI  - Defaming Rover: Error-Based Latent Rhetoric in the Medical Literature on Dog
      Bites.
AB  - This article examines the accuracy and rhetoric of reports by human health care
      professionals concerning dog bite injuries published in the peer-reviewed medical
      literature, with respect to nonclinical issues, such as dog behavior. A
      qualitative content analysis examined 156 publications between 1966 and 2015
      identified by terms such as "dog bite" or "dangerous dogs." The analysis revealed
      misinformation about human-canine interactions, the significance of breed and
      breed characteristics, and the frequency of dog bite-related injuries.
      Misinformation included clear-cut factual errors, misinterpretations, omissions,
      emotionally loaded language, and exaggerations based on misunderstood or
      inaccurate statistics or reliance on the interpretation by third parties of other
      authors' meaning. These errors clustered within one or more rhetorical devices
      including generalization, catastrophization, demonization, and negative
      differentiation. By constructing the issue as a social problem, these distortions
      and errors, and the rhetorical devices supporting them, mischaracterize dogs and
      overstate the actual risk of dog bites.

PMID- 29068712
TI  - Effects of Mycobacterium tuberculosis Mutant Strain Hsp16.3 Gene on Murine RAW
      264.7 Macrophage Autophagy.
AB  - Heat shock protein Hsp16.3 is closely related to latent Mycobacterium
      tuberculosis (MTB) infection and plays an important role in sustained survival
      when MTB is dormant. In this study, the Hsp16.3 gene mutant MTB H37Rv strain
      (Hsp16.3DeltaMTB) was obtained through gene recombination and infected into
      murine RAW 264.7 macrophages. Western blotting and immunofluorescence showed
      increased expression of the autophagy-related protein LC3, and transmission
      electron microscopy showed significantly increased macrophage autophagosomes,
      suggesting that Hsp16.3DeltaMTB facilitates murine macrophage autophagy. These
      findings have implications for preventing and controlling tuberculosis.

PMID- 29068713
TI  - Sexual Risk Behaviors Among Black Men Who Have Sex With Men Who Also Report
      Having Sex With Transgender Partners: Analysis of HIV Prevention Trials Network
      (HPTN) 061 Study.
AB  - HIV Prevention Trials Network (HPTN 061) study data of Black MSM were analyzed to
      determine characteristics associated with having transgender sexual partners
      (TGP) and the association of having TGP with sexual risk. Of 1,449 cisgender MSM,
      343(24%) reported also having TGP. MSM with TGP were more likely to be older,
      have a sexual orientation other than homosexual, have a history of incarceration,
      or have insufficient funds for necessities, but less likely to be HIV positive or
      report sex with men to health care providers. MSM with TGP were 3.67 times more
      likely to recently have 5+ new partners and 2.02 times more likely to report 6+
      condomless sexual acts. Since MSM with TGP reported not disclosing sex with men
      to health care providers, these men may need tailored HIV prevention and care.
      Future studies should examine differing sexual risks MSM take with sexual
      partners with different gender identities.

PMID- 29068714
TI  - Adaptation of the HIV/AIDS Self-Management Education Program for Men Who Have Sex
      With Men in Thailand: An Application of the ADAPT-ITT Framework.
AB  - This formative research aimed to describe the use of the ADAPT-ITT framework to
      modify the HASMEP for use with HIV-positive Thai men who have sex with men (MSM).
      We selected, adapted, and tested the acceptability and feasibility of the HASMEP
      intervention for delivery in an HIV clinic in Thailand. We chose to base our
      adaptation on the HASMEP that was initially developed in South Africa. The ADAPT
      ITT framework was used to guide the study. Our adaptation was informed by
      qualitative data collected during focus groups from 48 participants (40 HIV
      positive Thai MSM and 8 health care providers) and online surveys of Thai MSM.
      Findings of focus groups indicate that the HASMEP is feasible and acceptable when
      administered to the participants. The result of this work is an adapted HASMEP
      intervention and training materials. This study provides a strong foundation for
      further research on HIV/AIDS self-management in HIV-positive MSM.

PMID- 29068717
TI  - The Know*Now Project: Facilitated Serosorting in HIV-Status Sexual Partner
      Communication.
AB  - An intervention was conducted providing access to clinic-verified HIV test
      results via a secure, web-based informatics platform to facilitate sexual partner
      HIV-status communication. Participants (N = 28) were men who have sex with men
      (MSM; HIV- n = 8, HIV+ n = 8) and heterosexuals (Non-MSM, n = 12). Focus groups
      with same-group members explored interest in using the intervention and baseline
      attitudes and practices relevant to serosorting. HIV-negative participants
      overwhelmingly expressed interest, regardless of MSM status. Interest among HIV
      positive MSM was mixed. Six month follow-up interviews (n = 16) indicated 94% of
      all groups accessed the website, 69% had shown documented results to a sexual
      partner to initiate HIV-status discussion, and 88% reported future interest in
      using the 24/7 web-based tool with prospective sexual partners. Implications for
      future interventions facilitating HIV serosorting and sexual partner
      communication are discussed.

PMID- 29068715
TI  - Promoting Pre-exposure Prophylaxis to Prevent HIV Infections Among Sexual and
      Gender Minority Hispanics/Latinxs.
AB  - Sexual and gender minority Hispanics/Latinxs (henceforth: Latinxs) continue to be
      disproportionately impacted by HIV/AIDS in the U.S. Pre-exposure prophylaxis
      (PrEP) is a biomedical prevention approach which holds significant promise for at
      risk and vulnerable populations. We discuss barriers and facilitators to uptake
      of PrEP among sexual and gender minority Latinxs living in the U.S. through an
      ecosocial lens that takes into account structural, community, and individual
      contexts. The impact of immigration status on PrEP uptake emerges as a major and
      recurrent theme that must be understood and addressed by HIV prevention programs
      aiming to promote an inclusive strategy for sexual and gender minority Latinxs
      living in the U.S.

PMID- 29068719
TI  - A Critical Review of Health, Social, and Prevention Outcomes Associated With
      Employment for People Living With HIV.
AB  - A growing need has emerged among HIV service providers, policymakers, and
      researchers to understand ways in which employment, as a key social determinant
      of health, can be leveraged toward improved health outcomes among people living
      with HIV (PLHIV) and the prevention of HIV transmission. This critical review
      summarizes and assesses current research related to (a) the employment needs and
      challenges among populations disproportionately impacted by HIV, (b) the
      relationship between employment and important health outcomes associated with the
      HIV Care Continuum, and (c) implications for policy, service provision, and
      future research. As a first step to deepening an understanding of these issues,
      this analysis identifies gaps in knowledge to underscore the need and direction
      for future research so that well-targeted interventions can be designed and
      evaluated and more responsive policies can be developed to address the public
      health implications of the vocational development and employment needs of PLHIV.

PMID- 29068718
TI  - Barriers and Facilitators to the Implementation of a National HIV Linkage, Re
      Engagement, and Retention in Care Program.
AB  - The 2020 National HIV AIDS Strategy (NHAS) sets a target of 90% of diagnosed
      people living with HIV (PLWH) retained in HIV care. Access to Care (A2C) was a
      national HIV linkage, re-engagement, and retention in care program funded by AIDS
      United with support from the Corporation for National and Community Service that
      aimed to link and retain the most vulnerable PLWH into high-quality HIV care.
      This study explores the barriers and facilitators of implementing the A2C program
      from the perspective of program staff. Ninety-eight qualitative interviews were
      conducted with staff at implementing organizations over the 5 years of the
      project. Barriers included challenges with recruiting and retaining participants,
      staffing and administration, harmonizing partnerships, and addressing the basic
      and psychosocial needs of participants. Facilitators included strong
      relationships with partner organizations, flexible program models, and the
      passion and dedication of staff. Findings will inform the development of future
      programs and policy.

PMID- 29068716
TI  - Perspectives on HIV Testing Among WIC-Enrolled Postpartum Women: Implications for
      Intervention Development.
AB  - Low-income minority women are disproportionately represented among those living
      with HIV in the U.S and also at-risk for substance abuse and intimate partner
      violence-collectively called the SAVA syndemic-which may impede HIV testing
      uptake. Views about HIV testing were assessed among women (ages 18-29) enrolled
      in a federally funded nutrition program for women, infants, and children (WIC) in
      a large Mid-Atlantic city. A survey (n = 80) and three focus groups were
      conducted in WIC offices located in neighborhoods with high HIV prevalence. Among
      this primarily minority sample, most would be interested in getting an HIV test
      if offered at WIC. Benefits included knowing one's HIV status, convenience, and
      accessible location, while transportation and peer/partner encouragement were
      enabling factors. Barriers included privacy concerns and intimate partner
      violence. Findings will be used to design an intervention to promote HIV testing
      among women who attend WIC and that proactively addresses reported barriers.

PMID- 29068720
TI  - Detection and Molecular Characterization of Methicillin-Resistant Staphylococcus
      aureus from Table Eggs in Haripur, Pakistan.
AB  - Table eggs are nutritionally important food consumed globally. Despite being
      protected inside the hard shell and a semipermeable membrane, the egg contents
      may be contaminated with microbes and thus become a possible carrier of
      infectious agents to humans. A number of medically significant bacterial species
      such as Salmonella enterica, Listeria monocytogenes, and Yersinia enterocolitica
      have already been reported from table eggs. More important is the presence of
      antimicrobial-resistant bacterial strains in this food source. The present study
      was aimed at detection and characterization of Staphylococcus aureus from table
      eggs collected from different retail shops in Haripur city of Pakistan.
      Staphylococci were isolated from 300 eggs collected from December 2015 to May
      2016. S. aureus isolates were tested for antimicrobial susceptibility using broth
      microdilution and characterized using pulsed-field gel electrophoresis (PFGE),
      multilocus sequence typing (MLST), staphylococcal cassette chromosome mec
      (SCCmec) typing, and spa typing. The presence of Panton-Valentine leukocidin and
      antimicrobial resistance genes were detected using PCR. Staphylococci were
      isolated from 21.3% (64/300) of the table eggs tested. Of those, 59% (38/64) were
      identified as S. aureus, of which 33 (86.8%) were positive for mecA (MRSA,
      methicillin-resistant S. aureus). All MRSA were multidrug resistant (resistant to
      two or more antimicrobial classes), contained aac-aph (encoding aminoglycosides),
      and were pvl+. Using MLST, spa typing, and SCCmec typing, three genotypic
      patterns were assigned: ST8-t8645-MRSA-IV, associated with USA300; and ST772-t657
      MRSA-IV and ST772-t8645-MRSA-IV, both characteristic of the Bengal Bay community
      associated MRSA clone. Molecular typing by PFGE revealed that the bacterial
      population was highly homogenous with only two patterns observed. This study is
      the first report of detection of human-associated pvl+ MRSA from table eggs. The
      genetic similarities of MRSA present in the eggs to that of humans may suggest
      human to poultry transmission of MRSA via contamination.

PMID- 29068721
TI  - Adjunctive Use of Olanzapine in the Treatment of Avoidant Restrictive Food Intake
      Disorder in Children and Adolescents in an Eating Disorders Program.
AB  - OBJECTIVE: There is little information about the pharmacological treatment of
      avoidant and restrictive food intake disorder (ARFID), a challenging feeding
      disorder associated with marked impairment and developmental arrest. This brief
      clinical report seeks to fill this gap. METHODS: A retrospective chart review of
      nine patients with ARFID treated in an eating disorder (ED) program (residential,
      partial hospital, and intensive outpatient levels of care) with adjunctive
      olanzapine was undertaken. RESULTS: The mean initial and final olanzapine doses
      were 0.9 + 0.63 mg/day and 2.8 + 1.47 mg/day, respectively. There was a
      statistically significant difference in weight gain pre- versus post-olanzapine
      treatment (3.3 +/- 7.3 lbs vs. 13.1 +/- 7.9 lbs [2.99 +/- 6.62 lb SI vs. 11.88 +/
      7.17 lb SI], paired t-test (p < 0.04, t = -2.48). Clinically, adjunctive
      olanzapine was helpful for not only weight gain but also reduction of associated
      anxious, depressive, and cognitive symptoms. Clinical Global Impressions scale
      scores indicated marked improvement in patients receiving adjunctive olanzapine.
      CONCLUSION: These cases illustrate that judicious use of low-dose olanzapine,
      when used as an adjunct to other treatment modalities, may facilitate eating,
      weight gain, and the reduction of anxious, depressive, and cognitive symptoms in
      ARFID patients. Future randomized, placebo-controlled studies in ARFID are
      warranted.

PMID- 29068723
TI  - An Application of the Reasoned Action Approach to Bystander Intervention for
      Sexual Assault.
AB  - The high prevalence of sexual assault in US college campuses has led to a
      widespread implementation of bystander intervention programs aimed at preventing
      sexual assault. The current study examines predictors of college students'
      intentions to engage in bystander intervention through the theoretical lens of
      the reasoned action approach. An online survey with college students (N = 186)
      was conducted at a large Midwestern university. Our results indicated
      experiential attitudes, instrumental attitudes, descriptive norms, autonomy, and
      capacity, each positively associated with participants' intentions to intervene
      to stop a sexual assault. Against expectations, injunctive norms were unrelated
      to bystander intervention intentions. Finally, in addition to these main effects,
      an experiential attitude by autonomy interaction was also observed. The results
      are discussed with a focus on the theoretical and practical implications of our
      findings.

PMID- 29068722
TI  - High Occurrence of Methicillin-Resistant Staphylococcus aureus in Horses at
      Slaughterhouses Compared with Those for Recreational Activities: A Professional
      and Food Safety Concern?
AB  - The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) in horses
      and its zoonotic potential is poorly understood. The objective of this study is
      to provide data on the prevalence and genetic characteristics of MRSA isolated
      from horses on farms, at racecourses, and at slaughterhouses in Italy, using
      standard and molecular methods. In addition, we report the prevalence of MRSA in
      horse handlers. Among 388 horses tested by nasal swabs, 27 (7%) were positive for
      MRSA ST398 (t011, t899, t1255) and ST1 (t127). The prevalence of MRSA in horses
      tested at slaughterhouses was significantly higher (p < 0.001) compared with
      those tested on farms and racecourses. Five (7%) out of 67 staff members working
      in close contact with horses (2 from slaughterhouse, 2 from riding stable, and 1
      from racecourse) were carriers of MRSA ST398 (t011, t034) and ST1 (t127). The
      isolates from horses and humans carried SCCmec IVa or V and were pvl negative and
      pia positive. All the isolates from both horses and humans were resistant to at
      least two antimicrobial classes. The circulation of MRSA in horses and in humans
      working in close contact with them should be considered an emerging public health
      issue. In fact, it represents a potential risk for people who work in close
      contact with horses, and for horse meat consumers.

PMID- 29068724
TI  - Motivations of Young Adults for Improving Dietary Choices: Focus Group Findings
      Prior to the MENU GenY Dietary Change Trial.
AB  - BACKGROUND: Young adulthood is often associated with poor dietary habits that may
      increase risk of obesity and chronic diseases. As independence grows, little is
      known about strategies to help balance social, work, and education commitments
      that may override desires to incorporate healthful food choices. OBJECTIVE: In
      advance of a randomized trial to test an online intervention targeting young
      adults, we sought to identify views and experiences with healthy eating, and
      specifically, eating more fruits and vegetables. METHODS: We conducted 13 focus
      groups with 68 young adults in metropolitan Detroit (Henry Ford Health System)
      and rural Pennsylvania (Geisinger Health System). Randomly selected adults aged
      21 to 30 years, using health system automated data, were sent recruitment
      letters. Questions were grounded in social cognitive theory and self
      determination theory. Audiotapes were transcribed, content themes identified,
      coded, verified for reliability, and analyzed qualitatively. RESULTS: Young
      adults' efforts to eat healthfully included three major themes of (1) motivations
      to create a healthy lifestyle, teach by example, feel better, and manage weight
      and future health problems; (2) learning to eat well from childhood, independent
      living, and peers; and (3) strategies to eat better through planning, tracking,
      and commitment. DISCUSSION: We uncovered theory-based factors that facilitate
      healthy dietary behavior change among young adults, including managing their
      behavior through self-monitoring, goal-setting, small steps, meaningful
      reinforcements, and social opportunities. CONCLUSIONS: Targeted interventions
      encouraging reflection on personal values related to meaningful contemporary
      health benefits are likely to resonate with young adults, as will opportunities
      to receive and share new information.

PMID- 29068726
TI  - Promoting paediatric IV access.

PMID- 29068725
TI  - Calf Muscle Performance Deficits Remain 7 Years After an Achilles Tendon Rupture.
AB  - BACKGROUND: Optimizing calf muscle performance seems to play an important role in
      minimizing impairments and symptoms after an Achilles tendon rupture (ATR). The
      literature lacks long-term follow-up studies after ATR that describe calf muscle
      performance over time. PURPOSE: The primary aim was to evaluate calf muscle
      performance and patient-reported outcomes at a mean of 7 years after ATR in
      patients included in a prospective, randomized controlled trial. A secondary aim
      was to evaluate whether improvement in calf muscle performance continued after
      the 2-year follow-up. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS:
      Sixty-six subjects (13 women, 53 men) with a mean age of 50 years (SD, 8.5 years)
      were evaluated at a mean of 7 years (SD, 1 year) years after their ATR. Thirty
      four subjects had surgical treatment and 32 had nonsurgical treatment. Patient
      reported outcomes were evaluated with Achilles tendon Total Rupture Score (ATRS)
      and Physical Activity Scale (PAS). Calf muscle performance was evaluated with
      single-leg standing heel-rise test, concentric strength power heel-rise test, and
      single-legged hop for distance. Limb Symmetry Index (LSI = injured side/healthy
      side * 100) was calculated for side-to-side differences. RESULTS: Seven years
      after ATR, the injured side showed decreased values in all calf muscle
      performance tests ( P < .001-.012). Significant improvement in calf muscle
      performance did not continue after the 2-year follow-up. Heel-rise height
      increased significantly ( P = .002) between the 1-year (10.8 cm) and the 7-year
      (11.5 cm) follow-up assessments. The median ATRS was 96 (of a possible score of
      100) and the median PAS was 4 (of a possible score of 6), indicating minor
      patient-reported symptoms and fairly high physical activity. No significant
      differences were found in calf muscle performance or patient-reported outcomes
      between the treatment groups except for the LSI for heel-rise repetitions.
      CONCLUSION: Continued deficits in calf muscle endurance and strength remained 7
      years after ATR. No continued improvement in calf muscle performance occurred
      after the 2-year follow-up except for heel-rise height.

PMID- 29068727
TI  - Approaches for standardising best practice to reduce CRBSIs and CLABSIs.

PMID- 29068728
TI  - Tissue adhesive for vascular access devices: who, what, where and when?
AB  - Despite vascular access devices (VADs) being vital for patient care, device
      failure rates are unacceptably high with around 25% of central venous devices,
      and 30-40% of peripheral venous devices, developing complications that result in
      VAD failure. The use of tissue adhesive is a novel method of securing VADs and is
      gaining popularity, however the evidence base guiding its clinical use is still
      emerging. This article aims to review the types and properties of tissue
      adhesives, provide an overview of the existing evidence base, and discuss how
      tissue adhesives may be used in clinical practice.

PMID- 29068730
TI  - Yes, the cap's been scrapped.

PMID- 29068729
TI  - The consultant practitioner: an evolving role to meet changing NHS needs.
AB  - : Since the introduction of the consultant practitioner role, with its huge
      variability in purpose and context, it has had to evolve in response to the
      changing needs of the NHS to achieve sustainability and transformation of
      services. AIM: This article reflects on the relevance of the consultant
      practitioner role and the impact of an action learning set in hastening its
      evolution in one NHS foundation trust. METHOD: From a process of collective
      critical reflection on their practice, six consultant practitioners analysed the
      impact they have had on influencing services and empowerment of their patients.
      Additionally, they have analysed the impact of an externally facilitated action
      learning set as a catalyst for change. RESULTS: All six consultant practitioners
      recognised that working together through the learning set enabled them to be more
      influential and effective. It encouraged them to share their experiences of
      continuous service improvement and crystalised their views on the impact they
      have had in delivering the organisation's vision. CONCLUSION: From their critical
      reflection, the six consultant practitioners acknowledged the influence of the
      action learning set on accelerating their confidence and competence to lead, and
      evaluating new models of care delivery at scale and pace. They recognised how far
      they have travelled in achieving the four dimensions of the role and ultimately
      their impact on their local sustainability and transformation plan (STP) and
      their trust's vision.

PMID- 29068731
TI  - Nurses making history.

PMID- 29068732
TI  - Learning from the patient safety errors of the past.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses NHS Resolution's thematic review report analysing 5 years
      of cerebral palsy legal claims.

PMID- 29068734
TI  - Pass on your knowledge.

PMID- 29068733
TI  - Simulation on sensory impairment in older adults: nursing education.
AB  - Sensory impairments are identified as the most common chronic and disabling
      conditions of later life, impacting significantly on the quality of life and
      safety of older adults. Hospitals and care environments can present significant
      challenges to older adults with sensory impairments. Therefore, it is important
      to raise awareness on sensory and cognitive impairments with all health
      professionals, and nurses in particular, both to help develop an empathetic
      awareness of the impact of impairment and to minimise risk of adverse events.
      This article reports on a pedagogical innovation on the development and use of a
      simulation resource-primarily on sensory impairments in older adults-with first
      year nursing students in an undergraduate nursing programme in a Scottish
      university. The article also reports on students' reflections on their experience
      of participating in this simulation.

PMID- 29068735
TI  - Recruit and retain: planning to expand the mental healthcare workforce.
AB  - Emeritus Professor Alan Glasper, University of Southampton, discusses an
      initiative by health secretary Jeremy Hunt to expand the mental health workforce
      of the NHS in England.

PMID- 29068736
TI  - Emotional labour: learning from the past, understanding the present.
AB  - The number of nurses considering leaving the profession has continued to rise,
      and in many areas there is a nursing shortfall. For many of those leaving the
      profession, the decision results from workplace stress. This article examines the
      concept of emotional labour, which has been linked to compassion fatigue and
      subsequent burnout. Emotional labour is the term used to describe the process of
      displaying outward emotion that may not match our internal emotion; this
      dissonance can lead to highly stressful situations. The concept is explored from
      a genealogical perspective, specifically focusing on how gender, socio-political
      and health cultures have influenced the evolution of the discourse that defines
      how emotional labour is perceived, understood and valued. This article will
      identify what has shaped the discourse and how the historical influences have
      influenced perceptions. The article identifies that emotional labour has
      traditionally been viewed as women's work and has been undervalued. The influence
      of male nurses and the gradual decline of heavy industry has served to improve
      the understanding and value of the concept. Lessons from the past can inform the
      management of the stresses of emotional labour. Emotional labour is a recognised
      component of workplace stress and this article makes a number of recommendations
      for further research or management strategies, which may assist in the
      recognition and management of the stresses nurses face when delivering
      emotionally demanding care.

PMID- 29068737
TI  - From staff nurse to nurse consultant: Spiritual care part 7: Islam.
AB  - John Fowler, Educational Consultant, explores the role of clinically based nurses
      in providing care for patients who follow the principles of Islam.

PMID- 29068738
TI  - Support the support workers.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, examines the issue of the
      recruitment and retention of healthcare support workers, and considers what
      encourages staff to stay in a job.

PMID- 29068739
TI  - The experience of patients living with a vascular access device.

PMID- 29068740
TI  - Improving patient care and experience with vascular access devices.

PMID- 29068741
TI  - Attitudes towards three ultrasound-guided vascular access techniques in a
      paediatric emergency department.
AB  - BACKGROUND: although nurses often place peripheral intravenous (IV) catheters,
      little is known about their perceptions regarding use of ultrasound guidance.
      AIM: the authors aimed to determine paediatric emergency department nurses'
      attitudes toward ultrasound-guided IV access techniques and assessed practice
      change after training. METHOD: In a cross-sectional study of nurses, they had
      didactic and hands-on practice sessions, using three short-axis ultrasound-guided
      IV access techniques on gel models. Outcomes included likability and ease of
      learning and performing the techniques. A 3-month follow-up questionnaire
      assessed attitudes and behavioural changes. RESULTS: 18 nurses were enrolled and
      17 analysed. Participants liked all three techniques and thought they were easy
      to learn and perform. Eighty-two percent of the nurses used at least one
      technique clinically. The two-person self-guided technique was most preferred
      (65%) and used 3 months later (65%). CONCLUSIONS: nurses reported generally
      positive attitudes toward all three ultrasound-guided IV access techniques, but
      preferred the two-person self-guided technique. Owing to the small sample size,
      these results cannot be generalised and further research is needed.

PMID- 29068742
TI  - Experiences of peripheral IV insertion in hospital: a qualitative study.
AB  - Adult medical and surgical patients admitted to tertiary hospitals regularly have
      peripheral venous catheters (PVCs) inserted for their treatment. Anecdotally,
      patients report varying levels of pain and anxiety during the insertion
      procedure; however, lived experiences of patients are not well documented in the
      literature. The aim of this study was to gain an understanding of patients'
      experiences of PVC insertion. Some 10 participants were purposively sampled for
      semi-structured interviews, from the medical and surgical wards at a tertiary
      hospital in Queensland, Australia. Four key themes developed from the interview
      data: communication between the patient and the inserter; technique of device
      insertion; competence of the inserter; and location of the device. These themes
      informed practical ways that nurses might improve the patient experience,
      including: consultation with patients regarding device insertion preferences;
      siting the PVC in locations other than the antecubital fossa and hand; ensuring
      experienced and confident inserters are available to insert PVCs.

PMID- 29068743
TI  - Vascular access: a military perspective.

PMID- 29068746
TI  - Physiotherapy students' perceived stress, stressors, and reactions to stressors:
      A comparative study between Sweden and The Netherlands.
AB  - BACKGROUND AND PURPOSE: Studies of healthcare students report increased levels of
      stress, with academic pressures being the greatest source. The objective of this
      study was to examine the differences in the overall stress level, stressors, and
      reactions to stressors between physiotherapy students at the University of
      Gothenburg (GU) and those at the Hanze University of Applied Sciences (HUAS).
      METHODS: The Student-life Stress Inventory was used. The participants (n = 116)
      included physiotherapy students at GU and HUAS. The distribution of the
      questionnaire occurred during a regular lecture or in a lecture that was
      scheduled particularly for its distribution. RESULTS: At GU, 13.7% of the
      students rated their level of stress as mild, whereas 72.5% of them rated it as
      moderate. The corresponding values for HUAS students were 43.9% and 43.9%,
      respectively. This difference between two universities was significant (p =
      0.006). The total score of the subcategories indicated that the students at GU
      reported significantly higher levels of stressors (p = 0.027) and reactions to
      stressors (p = 0.003). However, there were no significant differences in the male
      participants between the universities. CONCLUSION: Female students in their three
      year educational program in Sweden experienced significantly more stress than
      Dutch female students in their four-year educational program.

PMID- 29068747
TI  - Clinical reasoning of Filipino physical therapists: Experiences in a developing
      nation.
AB  - Clinical reasoning is essential for physical therapists to engage in the process
      of client care, and has been known to contribute to professional development. The
      literature on clinical reasoning and experiences have been based on studies from
      Western and developed nations, from which multiple influencing factors have been
      found. A developing nation, the Philippines, has distinct social, economic,
      political, and cultural circumstances. Using a phenomenological approach, this
      study explored experiences of Filipino physical therapists on clinical reasoning.
      Ten therapists working in three settings: 1) hospital; 2) outpatient clinic; and
      3) home health were interviewed. Major findings were: a prescription-based
      referral system limited clinical reasoning; procedural reasoning was a commonly
      experienced strategy while diagnostic and predictive reasoning were limited;
      factors that influenced clinical reasoning included practice setting and the
      professional relationship with the referring physician. Physical therapists'
      responses suggested a lack of autonomy in practice that appeared to stifle
      clinical reasoning. Based on our findings, we recommend that the current
      regulations governing PT practice in the Philippines may be updated, and
      encourage educators to strengthen teaching approaches and strategies that support
      clinical reasoning. These recommendations are consistent with the global trend
      toward autonomous practice.

PMID- 29068745
TI  - Anticancer Activity and Molecular Mechanism of Polyphenol Rich Calophyllum
      inophyllum Fruit Extract in MCF-7 Breast Cancer Cells.
AB  - This study was conducted to investigate the anticancer effects and mechanism of
      Calophyllum inophyllum fruit extract against MCF-7 cells. C. inophyllum fruit
      extract was found to have markedly cytotoxic effect against MCF-7 cells in a dose
      dependent manner with the IC50 for 24 h of 23.59 ug/mL. Flow cytometry analysis
      revealed that C. inophyllum fruit extract mediated cell cycle at G0/G1 and G2/M
      phases, and MCF-7 cells entered the early phase of apoptosis. The expression of
      anti-apoptotic proteins Bcl-2 was decreased whereas the expression of the pro
      apoptotic protein Bax, cytochrome C and p53 were increased after treatment. C.
      inophyllum fruit extract led to apoptosis in MCF-7 cells via the mitochondrial
      pathway in a dose dependent manner. This is evidenced by the elevation of
      intracellular ROS, the loss of mitochondria membrane potential (Deltapsim), and
      activation of caspase-3. Meanwhile, dose-dependent genomic DNA fragmentation was
      observed after C. inophyllum fruits extract treatment by comet assay. This study
      shows that C. inophyllum fruits extract-induced apoptosis is primarily p53
      dependent and mediated through the activation of caspase-3. C. inophyllum fruit
      extract could be an excellent source of chemopreventive agent in the treatment of
      breast cancer and has potential to be explored as green anticancer agent.

PMID- 29068748
TI  - Recommendation system for immunization coverage and monitoring.
AB  - Immunization averts an expected 2 to 3 million deaths every year from diphtheria,
      tetanus, pertussis (whooping cough), and measles; however, an additional 1.5
      million deaths could be avoided if vaccination coverage was improved worldwide.
      11 Data source for immunization records of 1.5 M:
      http://www.who.int/mediacentre/factsheets/fs378/en/ New vaccination technologies
      provide earlier diagnoses, personalized treatments and a wide range of other
      benefits for both patients and health care professionals. Childhood diseases that
      were commonplace less than a generation ago have become rare because of vaccines.
      However, 100% vaccination coverage is still the target to avoid further
      mortality. Governments have launched special campaigns to create an awareness of
      vaccination. In this paper, we have focused on data mining algorithms for big
      data using a collaborative approach for vaccination datasets to resolve problems
      with planning vaccinations in children, stocking vaccines, and tracking and
      monitoring non-vaccinated children appropriately. Geographical mapping of
      vaccination records helps to tackle red zone areas, where vaccination rates are
      poor, while green zone areas, where vaccination rates are good, can be monitored
      to enable health care staff to plan the administration of vaccines. Our
      recommendation algorithm assists in these processes by using deep data mining and
      by accessing records of other hospitals to highlight locations with lower rates
      of vaccination. The overall performance of the model is good. The model has been
      implemented in hospitals to control vaccination across the coverage area.

PMID- 29068749
TI  - Combined effect of PCV10 and meningococcal C conjugate vaccination on meningitis
      mortality among children under five years of age in Brazil.
AB  - The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the
      Brazilian National Immunization Program in March 2010, scheduled at 2, 4, and 6
      months, with a booster at 12-15 months of age. The meningococcal C conjugate
      vaccine (MCC) was introduced in November 2010, scheduled at 3 and 5 months, with
      a booster dose at 12-15 months of age and no catch-up for older age groups. In
      this interrupted time-series analysis study, we used Brazilian mortality data
      from 2005 to 2015 for children under five years of age (excluding data from the
      state of Bahia) to assess the combined impact of these vaccines on the overall
      burden of meningitis mortality among children aged 0-23 months and 2-4 years, as
      defined using meningitis and meningococcemia specific International
      Classification of Diseases - tenth revision codes. Secular trends and seasonality
      were taken into account. We found significant reductions for both age groups
      relative to those observed for the comparison group of diseases, with immediate
      effects after the transition period (2010-2011) of 29.2% and 27.5% for children
      aged 0-23 months and 2-4 years, respectively. These immediate effects were
      sustained throughout the post-vaccination period (2012-2015). In total, 337
      deaths were averted by the combined effect of both vaccines, 238 (95%CI 169-319)
      for children aged 0-23 months and 99 (95%CI 56-144) for those aged 2-4 years.
      These results add strong evidence in support of investments in these vaccines by
      low and middle-income countries.

PMID- 29068751
TI  - Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma: American Society of
      Clinical Oncology Endorsement of the American Society for Radiation Oncology
      Evidence-Based Clinical Practice Guideline Summary.

PMID- 29068750
TI  - Long-Term Therapeutic Outcomes of Photodynamic Therapy-Based or Photocoagulation
      Based Treatments on Retinal Capillary Hemangioma.
AB  - BACKGROUND: Retinal capillary hemangioma (RCH) is a rare and refractory eye
      tumor. OBJECTIVE: The aim of this study was to investigate the therapeutic
      efficacy of two laser-based therapies for RCH, photodynamic therapy (PDT), and
      focal photocoagulation-based treatment. MATERIALS AND METHODS: This was a
      retrospective study. Eight RCH patients (10 eyes) receiving laser treatment and
      followed up from November 2011 to December 2016 in our hospital were selected and
      their medical records reviewed. Clinical results and correlations between various
      clinicodemographic factors and vision outcome were analyzed. RESULTS: A total of
      39 RCH tumor bodies were found and treated. Eleven sessions of PDT and 25
      sessions of photocoagulation were administered. Other treatments included five
      intravitreal injections of antivascular endothelial growth factor or
      triamcinolone acetonide and one vitreoretinal surgery. After the follow-up period
      of 54.3 +/- 29.8 months, 35 tumor bodies were stable or regressed, and 4 were
      recurrent. Vision was improved in four eyes, stable in one, and reduced in five
      relative to baseline. Photocoagulation was more likely to induce tumor bleeding
      than PDT (4 eyes vs. 1) and to increase subretinal fluid (3 eyes vs. 1). In
      correlation analysis, subretinal fluid accumulation was predictive of poor vision
      outcome (r = 0.69, p = 0.03). CONCLUSIONS: Photodynamic- and photocoagulation
      based therapies are both reasonably effective against most RCH tumor bodies, but
      PDT carries lower risks of bleeding and subretinal fluid refraction. Formation of
      subretinal fluid may predict poor vision outcome in RCH.

PMID- 29068753
TI  - Cancer Metastasis: A Reappraisal of Its Underlying Mechanisms and Their Relevance
      to Treatment.
AB  - Metastases are responsible for the vast majority of cancer-related deaths, but,
      despite intense efforts to understand their underlying mechanisms with the goal
      of uncovering effective therapeutic targets, treatment of metastatic cancer has
      progressed minimally. In this review, we examine the biological programs
      currently proposed to be key drivers of metastasis. On the basis of evidence from
      a growing body of research, we discuss to what extent the cellular and molecular
      mechanisms that are suggested to underlie cancer cell dissemination are specific
      to the metastatic process, as opposed to representing natural primary tumor
      progression. Our review highlights the contrast between the abundance of insight
      gained into the events that constitute the metastatic cascade and the paucity of
      therapeutic options.

PMID- 29068752
TI  - An Epidemiological Comparison of Elbow Injuries Among United States High School
      Baseball and Softball Players, 2005-2006 Through 2014-2015.
AB  - BACKGROUND: Pitching is a common mechanism of injury in baseball, with known risk
      factors for elbow injuries among adolescent pitchers. HYPOTHESIS: Elbow injury
      rates and mechanisms will differ between high school baseball and softball
      players. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level
      3. METHODS: Baseball- and softball-related injury data from the 2005-2006 through
      2014-2015 academic years were collected from the High School Reporting
      Information Online (RIO) Internet-based data collection tool. Athlete-exposure
      (AE) and injury data were collected by certified athletic trainers. Rate ratios
      (RRs) were calculated comparing injury rates in the 2 populations. Injury
      proportion ratios (IPRs) comparing elbow injuries in pitchers and nonpitchers
      were calculated as the proportion of all elbow injuries in pitchers divided by
      the proportion of all elbow injuries in nonpitchers. RESULTS: A total of 214
      elbow injuries in male baseball players occurred over 2,327,774 AEs, for an
      overall elbow injury rate of 0.92 per 10,000 AEs. A total of 75 elbow injuries
      were reported in female softball players over 1,731,644 AEs, for an overall rate
      of 0.43 per 10,000 AEs. The rate of elbow injury was significantly higher for
      baseball than softball (RR, 2.12; 95% CI, 1.64-2.77). A significantly greater
      proportion of elbow injuries in baseball were pitching-related compared with
      those from softball, with 50.2% occurring while pitching in baseball versus 11.0%
      in softball (IPR, 4.58; 95% CI, 2.35-8.93). If all injuries occurring during
      pitching were removed from both sports, the difference in elbow injury rate for
      baseball and softball would no longer be significant (RR, 1.19; 95% CI, 0.88
      1.62). CONCLUSION: The rate of elbow injuries is significantly higher in baseball
      than softball. This is attributable to differences in rates of pitching-related
      injuries between these 2 groups. CLINICAL RELEVANCE: These results demonstrate
      that overhand pitching increases risk of elbow injury in high school athletes.

PMID- 29068755
TI  - Caregiver Self-Esteem as a Predictor of Patient Relationship Satisfaction: A
      Longitudinal Study.
AB  - OBJECTIVE: Longitudinal assessment of patient-caregiver relationships will
      determine whether caregiver self-esteem determines patient relationship
      satisfaction at end of life. BACKGROUND: Research on close relationships and
      caregiving supports the idea that informal caregivers' self-esteem may influence
      their relationships with their terminally ill loved ones. However, this
      connection has not yet been investigated longitudinally, nor has it been applied
      specifically to care recipients' relationship satisfaction. METHODS: A sample of
      24 caregivers and 24 patients in a hospice home care program were recruited.
      Multiple patient and caregiver interviews were used to conduct a longitudinal
      study to measure fluctuations in patient health, changes in patient and caregiver
      relationship satisfaction, and self-esteem over a three-month period. RESULTS: An
      interaction between caregiver self-esteem and patient relationship satisfaction
      demonstrated the role that self-esteem plays between caregivers and patients
      enrolled in hospice care. Specifically, for patients with caregivers with low
      self-esteem, patient relationship satisfaction significantly decreased as the
      patient's physical health decreased, whereas for patients whose caregivers had
      high self-esteem, patient relationship satisfaction marginally increased during
      poorer physical health. DISCUSSION: High self-esteem may allow caregivers to
      overcome feelings of burden and maladaptive anticipatory grief to remain
      satisfied in their relationship with the patient. Caregiver self-esteem appears
      to play a role in fostering patient relationship satisfaction at the end of life.

PMID- 29068756
TI  - Long-Term Effect of Pulsed Nd-YAG Laser Combined with Exercise on Bone Mineral
      Density in Men with Osteopenia or Osteoporosis: 1 Year of Follow-Up.
AB  - BACKGROUND: A pulsed Nd-YAG laser is an effective physiotherapy modality used as
      a class IV high-intensity laser therapy (HILT). OBJECTIVE: The aim of this study
      is to investigate the efficacy of HILT alone or combined with exercise (HILT+EX)
      on bone mineral density (BMD) after 24 weeks and at 1 year of follow-up in men
      with osteopenia or osteoporosis. METHODS: One hundred men with osteopenia or
      osteoporosis (mean age, 53.78 [2.89] years; weight, 80.56 [7.33] kg; height 175
      [5.30] cm) participated in the study. The T-scores were <=-1.5. Patients were
      randomly assigned to four groups: HILT+EX (group I), placebo laser plus exercise
      (PL+EX; group II), HILT alone (HILT; group III), and PL (group IV). HILT was
      applied to the lower back and hip regions. Aerobic, weight-bearing, flexibility,
      strengthening, and balance exercises were performed three times per week for 24
      weeks. The measured outcomes were BMD of the L2-L4 spine and total hip.
      Measurements were taken before and after 24 weeks and at 1 year of follow-up.
      RESULTS: Lumbar and total hip BMD significantly increased post-treatment in the
      HILT+EX and PL+EX groups, but insignificantly in the HILT and PL groups. HILT+EX
      showed a significantly greater effect than PL+EX did on lumbar BMD, with no
      significant difference in total hip BMD, after 24 weeks and at follow-up.
      CONCLUSIONS: Although HILT alone did not effectively increase lumbar and total
      hip BMD, HILT combined with exercise was more effective than exercise alone at
      increasing lumbar BMD after 24 weeks of treatment, with effects lasting up to 1
      year.

PMID- 29068757
TI  - DACA and the Dream of Becoming a Physician.

PMID- 29068754
TI  - Electronic Cigarettes: Exposure and Use Among Pediatric Populations.
AB  - As an emerging inhalational exposure, electronic cigarettes (e-cigarettes) have
      rapidly gained public awareness with increasing use among adolescents and adults,
      leading to increased primary use by adolescents and increased secondhand exposure
      to emissions in infants, children, and adolescents. Although the long-term health
      risks for primary use and secondhand emission exposure are unknown, limited data
      from animal studies suggest that there is the potential for long-term lung injury
      and altered neurocognitive development in children with exposure to nicotine
      containing aerosols. In this pediatric-focused review, we discuss the history of
      e-cigarettes, the demographics of adolescent users, effects on health, and
      current legislative efforts to protect infants, children, and adolescents from
      exposure.

PMID- 29068759
TI  - Severe burns in a patient after out-of-hospital CPR.
AB  - We present a case of a patient after prolonged cardio-pulmonary resuscitation on
      hot asphalt, who suffered from first and second degree burns which worsened
      during hospitalization. The patient was treated with therapeutic hypothermia.
      Possible effect of therapeutic hypothermia on the course of burns is discussed.

PMID- 29068758
TI  - Effects of Biotin Supplementation During the First Week Postweaning Increases
      Pancreatic Islet Area, Beta-Cell Proportion, Islets Number, and Beta-Cell
      Proliferation.
AB  - During maturation, pancreatic islets achieve their full capacity to secrete
      insulin in response to glucose, undergo morphological changes in which alpha
      cells decrease and beta-cell mass increases, and they acquire the normal alpha-
      and beta-cell proportion changes that are important for islet functions later in
      life. In rodents, the first week of postweaning is critical for islet maturation.
      Multiple studies have documented the detrimental effects of several conditions on
      pancreatic maturation; however, few studies have addressed the use of
      pharmacological agents to enhance islet maturation. Biotin might have a potential
      action on islet maturation. Pharmacological concentrations of biotin have been
      found to modify islet morphology and function. In a previous study, we found that
      mice fed a biotin-supplemented diet for 8 weeks after weaning showed an increase
      in basal and glucose stimulated insulin secretion, enlarged islet size, and
      modified islet structure. In the present study, we investigated the effect of
      biotin on maturation features during the first week postweaning. Female BALB/cAnN
      Hsd mice were fed a control or a biotin-supplemented diet for 1 week after
      weaning. Compared with the control, biotin-supplemented mice showed an increase
      in pancreatic islet number and area in addition to an augmented proportion of
      beta-cells in the islet. These effects were related to an increase in beta-cell
      proliferation. No differences were found in insulin secretion, blood glucose
      concentrations, or serum insulin levels. These results indicate that biotin
      supplementation is capable of affecting beta-cell proliferation and might be a
      therapeutic agent for establishing strategies for regenerative medicine.

PMID- 29068761
TI  - Implicit Statistical Learning in Real-World Environments Leads to Ecologically
      Rational Decision Making.
AB  - Ecological rationality results from matching decision strategies to appropriate
      environmental structures, but how does the matching happen? We propose that
      people learn the statistical structure of the environment through observation and
      use this learned structure to guide ecologically rational behavior. We tested
      this hypothesis in the context of organic foods. In Study 1, we found that
      products from healthful food categories are more likely to be organic than
      products from nonhealthful food categories. In Study 2, we found that consumers'
      perceptions of the healthfulness and prevalence of organic products in many food
      categories are accurate. Finally, in Study 3, we found that people perceive
      organic products as more healthful than nonorganic products when the statistical
      structure justifies this inference. Our findings suggest that people believe
      organic foods are more healthful than nonorganic foods and use an organic-food
      cue to guide their behavior because organic foods are, on average, 30% more
      healthful.

PMID- 29068760
TI  - Which Road to Universal Coverage?

PMID- 29068762
TI  - Persian translation and validation of the Back Pain Functional Scale.
AB  - BACKGROUND: Patient-reported questionnaires provide important tools that can be
      utilized for the assessment of treatment efficacy in clinic and research. This
      study aimed to translate, cross-culturally adapt, and validate the Back Pain
      Functional Scale into Persian (BPFSp). METHODS: In this cross-sectional and
      prospective cohort of adult patients with low back pain (LBP), the translation
      and adaptation was performed according to standardized guidelines and pretested
      (n = 30). Psychometric testing was conducted with 100 patients with LBP and 50
      healthy subjects. Fifty patients with LBP recompleted the BPFSp at least 7 days
      later for test-retest reliability. RESULTS: The Persian adapted version of the
      BPFS was produced and validated. No floor and ceiling effects were revealed. The
      Cronbach'alpha coefficient for internal consistency was 0.895. The test-retest
      reliability was excellent (ICCagreement = 0.88, CI 95%: 0.80-0.93). The standard
      error of measurement and smallest detectable change were 9.9% and 27.5%,
      respectively. Construct convergent validity was demonstrated with the Persian
      Functional Rating Index (r = -0.77). Criterion validity was established with the
      Numerical Pain Rating Scale (r = -0.67). Total BPFSp scores discriminated between
      patients with LBP and healthy subjects. Factor structure showed two latent
      factors explaining a total variance of 60.1%. CONCLUSION: The BPFSp presented
      excellent reliability and validity for assessing the functional status in Persian
      speaking patients with LBP.

PMID- 29068763
TI  - The Humanizing Voice: Speech Reveals, and Text Conceals, a More Thoughtful Mind
      in the Midst of Disagreement.
AB  - A person's speech communicates his or her thoughts and feelings. We predicted
      that beyond conveying the contents of a person's mind, a person's speech also
      conveys mental capacity, such that hearing a person explain his or her beliefs
      makes the person seem more mentally capable-and therefore seem to possess more
      uniquely human mental traits-than reading the same content. We expected this
      effect to emerge when people are perceived as relatively mindless, such as when
      they disagree with the evaluator's own beliefs. Three experiments involving
      polarizing attitudinal issues and political opinions supported these hypotheses.
      A fourth experiment identified paralinguistic cues in the human voice that convey
      basic mental capacities. These results suggest that the medium through which
      people communicate may systematically influence the impressions they form of each
      other. The tendency to denigrate the minds of the opposition may be tempered by
      giving them, quite literally, a voice.

PMID- 29068765
TI  - Mechanisms of Renal Fibrosis.
AB  - Tubulointerstitial fibrosis is a chronic and progressive process affecting
      kidneys during aging and in chronic kidney disease (CKD), regardless of cause.
      CKD and renal fibrosis affect half of adults above age 70 and 10% of the world's
      population. Although no targeted therapy yet exists to slow renal fibrosis, a
      number of important recent advances have clarified the cellular and molecular
      mechanisms underlying the disease. In this review, I highlight these advances
      with a focus on cells and pathways that may be amenable to therapeutic targeting.
      I discuss pathologic changes regulating interstitial myofibroblast activation,
      including profibrotic and proinflammatory paracrine signals secreted by
      epithelial cells after either acute or chronic injury. I conclude by highlighting
      novel therapeutic targets and approaches with particular promise for development
      of new treatments for patients with fibrotic kidney disease.

PMID- 29068764
TI  - In Pursuit of the Most Cost-Effective Pediatric Laparoscopic Appendectomy: The
      Effect of Disposable Instrument Choice on Operative Time and Surgeon-Controllable
      Cost.
AB  - BACKGROUND: There is a movement toward cost savings in healthcare worldwide.
      Surgeons can affect two main cost variables in an operation (controllable cost):
      disposables and time. Our hypothesis is that increasing disposable costs do not
      change outcome or operative time, but simply increases controllable cost.
      METHODS: We retrospectively reviewed patients younger than the age of 18 years
      undergoing laparoscopic appendectomies for nonperforated appendicitis from
      January 2013 to November 2016. Data obtained included demographic information in
      addition to intraoperative details, including disposables used and associated
      cost, resident participation, operative time, and final pathology. Patients were
      excluded if perforation was present as confirmed by operative findings or
      pathology (Kansas City definition). Patients were also excluded if concurrent
      procedures were performed during the appendectomy. RESULTS: We reviewed 918
      patients and excluded 288 for a total of 690. Disposable cost, operative time,
      and complications were compared between cases with a resident present and those
      without. Residents did not increase the use of disposables, but did increase
      operative time and therefore the total controllable cost. Transumbilical
      laparoscopic-assisted technique was significantly faster with lower controllable
      cost when compared with all other methods. Using disposable trocars with an
      endostapler was the second fastest and second lowest controllable cost and
      retained a significant difference when compared with most other methods. Endoloop
      methods did not show overall controllable cost savings versus the vast majority
      of methods. CONCLUSIONS: To maximize controllable cost savings, we recommend a
      transumbilical laparoscopic-assisted appendectomy or a standard three-port
      laparoscopic appendectomy, with disposable trocars and the endostapler.

PMID- 29068766
TI  - The Role of Autophagy in the Heart.
AB  - Autophagy is an evolutionarily conserved mechanism by which cytoplasmic elements
      are degraded intracellularly. Autophagy has also emerged as a major regulator of
      cardiac homeostasis and function. Autophagy preserves cardiac structure and
      function under baseline conditions and is activated during stress, limiting
      damage under most conditions. It reduces injury and preserves cardiac function
      during ischemia. It also reduces chronic ischemic remodeling and mediates the
      cardiac adaptation to pressure overload by restricting misfolded protein
      accumulation, mitochondrial dysfunction, and oxidative stress. Impairment of
      autophagy is involved in the development of diabetes and aging-induced cardiac
      abnormalities. Autophagy defects contribute to the development of cardiac
      proteinopathy and doxorubicin-induced cardiomyopathy. However, massive activation
      of autophagy may be detrimental for the heart in certain stress conditions, such
      as reperfusion injury. In this review, we discuss recent evidence supporting the
      important role of autophagy and mitophagy in the regulation of cardiac
      homeostasis and adaptation to stress.

PMID- 29068767
TI  - Reliability and a correlational analysis of the 6MWT, ten-meter walk test, thirty
      second sit to stand, and the linear analog scale of function in patients with
      head and neck cancer.
AB  - OBJECTIVE: The purpose of this study was to establish the test-retest reliability
      of and relationships between various measures of physical function in a cohort of
      individuals in the early treatment stages for head and neck cancer (HNC).
      METHODS: The Six-Minute Walk Test (6MWT), 10-Meter Walk Test (10MWT), 30-Second
      Sit to Stand (30STS), and Linear Analog Scale of Function (LASF) were
      administered to 42 participants with a diagnosis of HNC. Test-retest reliability
      and correlations between the measures are reported. RESULTS: The 6MWT, 10MWT,
      30STS, and LASF demonstrate excellent test-retest reliability (ICC = 0.901
      0.960). The 6MWT exhibits a moderate to good relationship with the 10MWT (r =
      0.684, p < 0.001), whereas the relationship between the 30STS and the 6MWT (r =
      0.407, p = 0.007) and 10MWT (r = 0.322, p = 0.038) is fair. The LASF does not
      correlate significantly with the 6MWT, 10MWT, or 30STS. CONCLUSIONS: The 6MWT,
      10MWT, 30STS, and LASF are reliable measurement instruments for patients treated
      for HNC. The 6MWT, 10MWT, and 30STS are significantly correlated suggesting they
      may measure subconstructs of physical function. The LASF does not correlate
      significantly with the 6MWT, 10MWT and 30STS in this sample.

PMID- 29068768
TI  - Exploring the factors that influence physician technostress from using mobile
      electronic medical records.
AB  - This paper proposes an integrated model for investigating how physicians'
      perceived individual and technology characteristics affect their technological
      stress (technostress) that is derived from using mobile electronic medical
      records (MEMRs). Individual characteristics comprise constructs of mobile self
      efficacy and technology dependence, whereas perceived technology characteristics
      comprise constructs of perceived usefulness, complexity, and reliability. We
      employed the survey method to collect 158 valid questionnaires from physicians
      working at three branch hospitals to determine perceptions regarding MEMRs,
      yielding a response rate of 33.62%. Partial least squares, a structural equation
      modeling technique, was used for model examination and hypothesis testing. The
      results show that physicians have a low perception of MEMR dependence and
      technostress. Furthermore, physicians' perceived MEMR technology dependency,
      mobile self-efficacy, and complexity were proven to significantly affect
      physician technostress when using MEMRs, whereas perceived usefulness and
      reliability were not. The explanatory power of the research model reached 67.8%.
      The results of this study provide valuable insights and significant knowledge for
      technostress in health care, particularly from academic and practical
      perspectives.

PMID- 29068769
TI  - Negotiating the social and medical dangers of abortion in Addis Ababa: An
      exploration of young, unmarried women's abortion-seeking journeys.
AB  - Unmarried, young women constitute a significant proportion of women who undergo
      unsafe abortion in Ethiopia. Based on material from an ethnographic study, the
      experiences of young, unmarried women who had been admitted to the hospital in
      the aftermath of an unsafe, clandestine abortion are explored in this article.
      The routes the young women followed in their search of abortion services and the
      concerns and realities they had to negotiate and navigate are at the fore.
      Despite their awareness of the dangers involved in clandestine and illegal
      abortion, the young women felt they had no choice but to use medically unsafe
      abortion services. Two reasons for this are highlighted: such services were
      affordable and, significantly, they were considered socially safe in that the
      abortion remained unknown to others and the stigma of abortion and its
      consequences could hence be avoided. In situations in which choices had to be
      made, social safety trumped medical safety. This indicates a need for abortion
      services that address both the medical and social safety concerns of young women
      in need of such services.

PMID- 29068770
TI  - Determinants of driving under the influence of alcohol or drugs among latino
      immigrants in miami-dade county, florida.
AB  - Little is known about the pre- and postimmigration drinking and drunk- and
      drugged-driving behavior of Latino immigrants. Despite showing risky drinking
      behaviors, many recent immigrants of low socioeconomic status (SES) do not drive
      while impaired by alcohol (DWI) due largely to limited access to a vehicle. This
      effort examines the DWI and driving while impaired by drugs (DWID) behaviors of
      Latino immigrants who have access to a vehicle. Data came from an ongoing
      longitudinal sample of Latino immigrants to Miami-Dade County, Florida. Bivariate
      analyses and logistic regression were applied. Preimmigration DWI and DWID was
      the best predictor of postimmigration DWI and DWID. Future interventions should
      make efforts to (a) identify immigrants who had DWI and DWID in their country of
      origin and (b) design and deliver specific and culturally relevant messages to
      persuade them not to engage in DWI and DWID after immigration.

PMID- 29068771
TI  - Investigation of a Worker Death While Agitating Manure in a Non-enclosed Storage.
AB  - An in-depth investigation of an unusual, non-enclosed manure storage hydrogen
      sulfide-induced fatality on a Holstein beef production operation is presented.
      The case involved several factors that likely played a role in the young farmer's
      death. These included zero wind movement, a reported temperature inversion in the
      area, relatively cool late summer outdoor temperatures on the morning of the
      incident, higher outdoor temperatures the week prior, and a high by-product steer
      ration containing ingredients that contributed significant sulfur content to the
      stored manure. Recommendations are offered for future research to determine the
      combinations of conditions and inputs that have potential to increase human and
      animal risk around manure storage structures. Based on this case and others
      recently documented showing unsafe levels of hydrogen sulfide being released from
      similar outdoor storages, it is critical that agricultural industry experts and
      input suppliers continue to analyze risk and consequences associated with new
      management practices, processes, inputs (including feed ingredients and animal
      bedding), machines, and other technology developed to support animal agriculture.
      Production practice and educational guidance are also offered based on this case
      and published literature.

PMID- 29068772
TI  - Examining the efficacy of an mHealth media literacy education program for sexual
      health promotion in older adolescents attending community college.
AB  - OBJECTIVE: To determine the feasibility of a mobile health (mHealth), media
      literacy education program, Media Aware, for improving sexual health outcomes in
      older adolescent community college students. PARTICIPANTS: 184 community college
      students (ages 18-19) participated in the study from April-December 2015.
      METHODS: Eight community college campuses were randomly assigned to either the
      intervention or a wait-list control group. Student participants from each campus
      completed web-based pretest and posttest questionnaires. Intervention group
      students received Media Aware in between questionnaires. RESULTS: Several
      intervention effects of the Media Aware program were significant, including
      reducing older adolescents' self-reported risky sexual behaviors; positively
      affecting knowledge, attitudes, normative beliefs, and intentions related to
      sexual health; and increasing media skepticism. Some gender differences in the
      findings were revealed. CONCLUSIONS: The results from this study suggest that
      Media Aware is a promising means of delivering comprehensive sexual health
      education to older adolescents attending community college.

PMID- 29068773
TI  - Handling Challenges Inherent in the Hospice Chaplain Role.
AB  - With an increasing number of terminal patients in the United States dying in the
      context of hospice, the role that hospice chaplains play in providing spiritual
      care for patients and their families is important to examine. The hospice
      chaplain role requires careful navigation of the development of relationships
      that may end abruptly, the expectations of hospice organizations, and the needs
      of both patients and families. The current study uses the concept of competing
      role dialectics to further our understanding of the challenges chaplains face as
      they enact this crucial role. Data from 45 current and former hospice chaplains
      reveal four major role tensions hospice chaplains must develop strategies to
      handle: fostering relationships versus fostering autonomy, acting as team members
      versus acting as individuals, serving the family unit as a whole versus serving
      particular family members, and following the agendas of patients and families
      versus following one's own agenda.

PMID- 29068774
TI  - Guatemalan women achieve ideal family size: Empowerment through education and
      decision-making.
AB  - Women's empowerment in family planning strengthens families and communities.
      Using 2014/2015 Demographic and Health Surveys data from 7,168 Guatemalan women,
      ages 35 and above with at least one living child, we examined indicators of
      empowerment in four domains - economic, educational, social, and contraceptive -
      and their relation to the number of living children compared to the ideal number
      of children. We reveal our analysis showing that economic, educational, and
      social empowerment predicted achieving the preferred number of children.
      Education and control over their own income are two critical empowerment factors
      for Guatemalan women.

PMID- 29068775
TI  - Children exposed to alcohol-related problems and DSM-5 alcohol use disorder in
      San Juan, Puerto Rico.
AB  - This article estimates the proportion of children (17 and younger) exposed to an
      adult with an alcohol problem or alcohol use disorder (AUD) in San Juan, Puerto
      Rico. Data are from a household random sample of 1,510 individuals 18-64 years of
      age. A total of 20.9% of children in sample households were exposed to an adult
      with an alcohol problem, and 5.7% were exposed to an adult with DSM-5 AUD. These
      considerable proportions suggest that alcohol treatment and family support
      programs should include help for adults in the family, and special support for
      exposed children in the household.

PMID- 29068776
TI  - Linkage between HIV diagnosis and care: Understanding the role of gender in a
      Northern Province in Vietnam.
AB  - Early linkage to HIV care is associated significantly with improved patient
      outcomes and reduced the risk of HIV transmission. However, delays between HIV
      diagnosis and registering for care have prevailed in Vietnam. The aim of
      researchers in this study is to examine linkages to care for individuals newly
      diagnosed with HIV in 2014, especially to highlight the impact of gender upon
      these linkages in a Northern Province of Ninh Binh. We collected secondary data
      of all 125 eligible HIV positive people diagnosed in 2014 and conducted a gender
      based descriptive analysis of their registration to care within 6 months.
      Nineteen in-depth interviews and two focus group discussions were completed. We
      found that women accounted for one-third of newly diagnosed cases (42/125), but
      initiated HIV treatment at an earlier stage of HIV disease than men (65% women at
      stage 1, 2 versus 31% in men). Stigma and discrimination was greater among women
      while inadequate awareness of treatment was greater for men. Dissatisfaction with
      HIV testing and counseling and no or passive referral to treatment were other
      barriers for both the genders for enrolling in care services after diagnosis.

PMID- 29068778
TI  - Psychology's Renaissance.
AB  - In 2010-2012, a few largely coincidental events led experimental psychologists to
      realize that their approach to collecting, analyzing, and reporting data made it
      too easy to publish false-positive findings. This sparked a period of
      methodological reflection that we review here and call Psychology's Renaissance.
      We begin by describing how psychologists' concerns with publication bias shifted
      from worrying about file-drawered studies to worrying about p-hacked analyses. We
      then review the methodological changes that psychologists have proposed and, in
      some cases, embraced. In describing how the renaissance has unfolded, we attempt
      to describe different points of view fairly but not neutrally, so as to identify
      the most promising paths forward. In so doing, we champion disclosure and
      preregistration, express skepticism about most statistical solutions to
      publication bias, take positions on the analysis and interpretation of
      replication failures, and contend that meta-analytical thinking increases the
      prevalence of false positives. Our general thesis is that the scientific
      practices of experimental psychologists have improved dramatically.

PMID- 29068777
TI  - Predictors and outcomes of excess gestational weight gain among low-income
      pregnant women.
AB  - Low-income women were interviewed and their post-natal records were retrieved (n
      = 160) to assess prevalence of excess gestational weight gain and its socio
      demographic predictors. More than half of the women (64%) gained excess weight
      during pregnancy, with an average of 10 lbs in excess of Institute of Medicine
      guidelines. Logistic regression indicated that women that started pregnancy at an
      obese body mass index; who were African American or having an unplanned pregnancy
      were at significant risk of gaining excess weight in pregnancy. Intervention to
      prevent excess weight gain during pregnancy is critical in addressing obesity
      epidemic in the United States and worldwide.

PMID- 29068781
TI  - Healthy Kids.

PMID- 29068782
TI  - Analysis of the cause of recurrent pregnancy loss in Vietnam: A cross-sectional
      study.
AB  - Recurrent pregnancy loss (RPL) is a physical and mental burden for women. In
      Vietnam, exploring the cause of miscarriages is still a challenge to clinical
      physicians. We aimed to investigate the etiology of RPL in the National Hospital
      of Obstetrics and Gynecology in Vietnam from 2012 to 2014. The cross-sectional
      study included 301 pregnant women with a history of RPL. The patients were
      examined and offered medical testing to determine the cause(s). Based on the
      testing, we determined causation for (11.29%) patients who had positive scores on
      an antiphospholipid antibody test and who were subsequently successfully treated
      for their problem.

PMID- 29068785
TI  - Adjuvant Pazopanib Does Not PROTECT Against Recurrence of High-Risk, Initially
      Localized Renal Cell Cancer but Does Provide Novel Insights.

PMID- 29068783
TI  - MicroRNA Expression-Based Model Indicates Event-Free Survival in Pediatric Acute
      Myeloid Leukemia.
AB  - Purpose Children with acute myeloid leukemia (AML) whose disease is refractory to
      standard induction chemotherapy therapy or who experience relapse after initial
      response have dismal outcomes. We sought to comprehensively profile pediatric AML
      microRNA (miRNA) samples to identify dysregulated genes and assess the utility of
      miRNAs for improved outcome prediction. Patients and Methods To identify miRNA
      biomarkers that are associated with treatment failure, we performed a
      comprehensive sequence-based characterization of the pediatric AML miRNA
      landscape. miRNA sequencing was performed on 1,362 samples-1,303 primary, 22
      refractory, and 37 relapse samples. One hundred sixty-four matched samples-127
      primary and 37 relapse samples-were analyzed by using RNA sequencing. Results By
      using penalized lasso Cox proportional hazards regression, we identified 36
      miRNAs the expression levels at diagnosis of which were highly associated with
      event-free survival. Combined expression of the 36 miRNAs was used to create a
      novel miRNA-based risk classification scheme (AMLmiR36). This new miRNA-based
      risk classifier identifies those patients who are at high risk (hazard ratio,
      2.830; P <= .001) or low risk (hazard ratio, 0.323; P <= .001) of experiencing
      treatment failure, independent of conventional karyotype or mutation status. The
      performance of AMLmiR36 was independently assessed by using 878 patients from two
      different clinical trials (AAML0531 and AAML1031). Our analysis also revealed
      that miR-106a-363 was abundantly expressed in relapse and refractory samples, and
      several candidate targets of miR-106a-5p were involved in oxidative
      phosphorylation, a process that is suppressed in treatment-resistant leukemic
      cells. Conclusion To assess the utility of miRNAs for outcome prediction in
      patients with pediatric AML, we designed and validated a miRNA-based risk
      classification scheme. We also hypothesized that the abundant expression of miR
      106a could increase treatment resistance via modulation of genes that are
      involved in oxidative phosphorylation.

PMID- 29068784
TI  - Predictors of Posthospital Transitions of Care in Patients With Advanced Cancer.
AB  - Purpose Patients with advanced cancer experience potentially burdensome
      transitions of care after hospitalizations. We examined predictors of discharge
      location and assessed the relationship between discharge location and survival in
      this population. Methods We conducted a prospective study of 932 patients with
      advanced cancer who experienced an unplanned hospitalization between September
      2014 and March 2016. Upon admission, we assessed patients' physical symptoms
      (Edmonton Symptom Assessment System) and psychological distress (Patient Health
      Questionnaire-4). The primary outcome was discharge location (home without
      hospice, postacute care [PAC], or hospice [any setting]). The secondary outcome
      was survival. Results Of 932 patients, 726 (77.9%) were discharged home without
      hospice, 118 (12.7%) were discharged to PAC, and 88 (9.4%) to hospice. Those
      discharged to PAC and hospice reported high rates of severe symptoms, including
      dyspnea, constipation, low appetite, fatigue, depression, and anxiety. Using
      logistic regression, patients discharged to PAC or hospice versus home without
      hospice were more likely to be older (odds ratio [OR], 1.03; 95% CI, 1.02 to
      1.05; P < .001), live alone (OR, 1.95; 95% CI, 1.25 to 3.02; P < .003), have
      impaired mobility (OR, 5.08; 95% CI, 3.46 to 7.45; P < .001), longer hospital
      stays (OR, 1.15; 95% CI, 1.11 to 1.20; P < .001), higher Edmonton Symptom
      Assessment System physical symptoms (OR, 1.02; 95% CI, 1.003 to 1.032; P < .017),
      and higher Patient Health Questionnaire-4 depression symptoms (OR, 1.13; 95% CI,
      1.01 to 1.25; P < .027). Patients discharged to hospice rather than PAC were more
      likely to receive palliative care consultation (OR, 4.44; 95% CI, 2.12 to 9.29; P
      < .001) and have shorter hospital stays (OR, 0.84; 95% CI, 0.77 to 0.91; P <
      .001). Patients discharged to PAC versus home had lower survival (hazard ratio,
      1.53; 95% CI, 1.22 to 1.93; P < .001). Conclusion Patients with advanced cancer
      who were discharged to PAC facilities and hospice had substantial physical and
      psychological symptom burden, impaired physical function, and inferior survival
      compared with those discharged to home. These patients may benefit from
      interventions to enhance their quality of life and care.

PMID- 29068786
TI  - Effect of sub-chronic ferrous sulfate treatment on motor skills, hematological
      and biochemical parameters in rats.
AB  - This study investigated the effects of ferrous sulfate (FeSO4) on motor skills,
      hematological and biochemical parameters in rats. Adult rats were treated with
      dose of iron (280 mg/L, per os) for 15 consecutive days in drinking water. No
      significant difference was noticed for the motor skills in the stationary beam (p
      = 0.23) and suspended string tests (p = 0.48) between control and iron-treated
      rats. However, iron-treated rats showed a significant increase in white blood
      cells count (p = 0.01), mean corpuscular volume values (p = 0.02) and decrease in
      frequency of peristaltic contractions of the fragment of the intestine (in vitro)
      compared to control rats (p = 0.01). No significant difference in plasma iron
      level (p = 0.89) and transferrin amount were observed after iron treatment (p =
      0.65). The findings indicate that iron treatment at 280 mg/L, per os for 15
      consecutive days in adult rats induced increase of hematological parameters (sign
      of a potential inflammation), but not motor skills deficit.

PMID- 29068787
TI  - Impact of work pressure, work stress and work-family conflict on firefighter
      burnout.
AB  - Little research has explored burnout and its causes in the American fire service.
      Data were collected from career firefighters in the southeastern United States (n
      = 208) to explore these relationships. A hierarchical regression model was tested
      to examine predictors of burnout including sociodemographic characteristics
      (model 1), work pressure (model 2), work stress and work-family conflict (model
      3) and interaction terms (model 4). The main findings suggest that perceived work
      stress and work-family conflict emerged as the significant predictors of burnout
      (both p < .001). Interventions and programs aimed at these predictors could
      potentially curtail burnout among firefighters.

PMID- 29068788
TI  - Vulnerable populations of patients and practitioners: Bound by limited resources.

PMID- 29068790
TI  - Yogic practices on oxidative stress and of antioxidant level: a systematic review
      of randomized controlled trials.
AB  - Background Many clinical trials have evaluated the oxidative stress reduction and
      enhancement of antioxidant status following yogic practices, but a review has not
      been reported earlier. Present study is designed to systematically review the
      effect of yogic practices on oxidative stress and antioxidant status. Content
      Using the MEDLINE, EMBASE SCOPEMED, and Indian database electronic searches were
      performed through August 2016 using the keywords yoga AND oxidative stress OR
      antioxidant which yielded 97 studies. Selections were made to include only
      experimental studies written in English, published in peer-reviewed journals and
      investigating the effects of regular yogic practices on oxidative stress and
      antioxidant status in these studies. Summary and outlook Search yielded a total
      of 97 trials, 11 met rigorous criteria for final systematic review. Healthy
      population showed overall enhancement of antioxidant status and reduced oxidative
      stress following yogic practices. Diabetic patients showed increased glutathione,
      vitamin C content and superoxide dismutase activity and decreased malondialdehyde
      content following yogic practices. Prediabetic and hypertensive patients showed
      reduced malondialdehyde content following yogic practices. Renal disease patients
      showed decreased protein oxidation, and increased superoxide dismutase activity
      following yogic practices. Regular yogic practices can improve antioxidants and
      reduce oxidative stress in healthy, diabetic, prediabetic, hypertensive and renal
      disease patients. Studies on other disease population have rarely been reported
      and studies are very few to conclude strongly.

PMID- 29068789
TI  - The beneficial effects of pumpkin extract on atherogenic lipid, insulin
      resistance and oxidative stress status in high-fat diet-induced obese rats.
AB  - Background Prevention and treatment of obesity is a way to reduce cardiovascular
      disease, diabetes and depression. Pumpkin as a favorable plant has different
      properties notably antioxidant, lipid-lowering and anti-diabetic potential. The
      aim of this study was to assess the anti-obesity effects of pumpkin in diet
      induced obese rats. Methods Thirty adult male Wistar rats were randomly divided
      into five groups (n=6) of healthy control, dietary fatty control rats, and three
      experimental dietary fatty rats that received hydro-alcoholic extract of pumpkin
      once daily at doses 100 and 200 and 400 mg/kg, respectively. At the end of 6
      weeks, lipid profile, atherogenicity, liver enzymes, and oxidative stress status
      were measured. Results Pumpkin in a dose-dependent manner dramatically decreased
      triglycerides and low-density lipoprotein, and liver enzymes while high-density
      lipoprotein was markedly increased in treated groups. Pumpkin also increased
      glutathione level in comparison with obese control group. Conclusions Pumpkin
      ameliorated oxidative stress and dyslipidemia in obese rats, leading to decrease
      cardiovascular disease risk in obesity.

PMID- 29068791
TI  - Transfusion-associated necrotizing enterocolitis re-evaluated: a systematic
      review and meta-analysis.
AB  - CONTEXT: Significant controversy exists surrounding the possible association
      between recent packed red blood cell (PRBC) transfusion and the subsequent
      development of necrotizing enterocolitis (NEC) in infants. Previous studies and
      meta-analyses reporting a statistically significant association led to a practice
      change to withhold enteral feeds in the peri-transfusion period in many centers
      in an effort to prevent NEC; however, results from more recent studies do not
      support the existence of an association and, thus, question the validity of this
      practice change. OBJECTIVE: This study aimed to perform a systematic review and
      meta-analysis to determine whether exposure to recent PRBC transfusion (defined
      as within 48 h) is associated with the subsequent development of NEC stage >=II
      (Bell's criteria) in infants. METHODS: Medline, Embase, CINAHL, and the Cochrane
      Library were searched from inception to October 7, 2015. A gray literature search
      was also performed. Studies comparing the risk of NEC in infants exposed and
      unexposed to recent PRBC transfusion were included. Thirteen studies met
      eligibility criteria, and 10 (n=15,675 infants) were included in the meta
      analysis. Three authors independently extracted data, and meta-analysis was
      performed using a random effects model. RESULTS: We found a statistically
      significant 45% reduction in the unadjusted odds of NEC in infants exposed to a
      recent PRBC transfusion (odds ratio=0.55, 95% confidence interval=0.31-0.98).
      CONCLUSION: Our results show a protective effect of recent PRBC transfusion on
      the subsequent development of NEC. The practice of withholding enteral feeds
      during the peri-transfusion period should be re-evaluated in light of these
      results.

PMID- 29068792
TI  - Neurodevelopmental and neurological effects of chemicals associated with
      unconventional oil and natural gas operations and their potential effects on
      infants and children.
AB  - Heavy metals (arsenic and manganese), particulate matter (PM), benzene, toluene,
      ethylbenzene, xylenes (BTEX), polycyclic aromatic hydrocarbons (PAHs) and
      endocrine disrupting chemicals (EDCs) have been linked to significant
      neurodevelopmental health problems in infants, children and young adults. These
      substances are widely used in, or become byproducts of unconventional oil and
      natural gas (UOG) development and operations. Every stage of the UOG lifecycle,
      from well construction to extraction, operations, transportation and distribution
      can lead to air and water contamination. Residents near UOG operations can suffer
      from increased exposure to elevated concentrations of air and water pollutants.
      Here we focus on five air and water pollutants that have been associated with
      potentially permanent learning and neuropsychological deficits,
      neurodevelopmental disorders and neurological birth defects. Given the profound
      sensitivity of the developing brain and central nervous system, it is reasonable
      to conclude that young children who experience frequent exposure to these
      pollutants are at particularly high risk for chronic neurological diseases. More
      research is needed to understand the extent of these concerns in the context of
      UOG, but since UOG development has expanded rapidly in recent years, the need for
      public health prevention techniques, well-designed studies and stronger state and
      national regulatory standards is becoming increasingly apparent.

PMID- 29068794
TI  - Results from a drug utilization study of extended release quetiapine fumarate
      prescribed by psychiatrists as treatment for major depressive disorder in
      selected countries in the European Union.
AB  - This multicenter, observational drug utilization (DU) study (NCT01594996)
      investigated the profile of patients and specialist providers who prescribed
      extended release quetiapine fumarate (quetiapine XR) for treatment of major
      depressive disorder (MDD) across five European countries (Germany, Italy,
      Romania, Spain, and Sweden). A DU data abstraction form captured information on
      the characteristics of physicians, patients, and drugs utilized in the medical
      management of depressive episodes in MDD, where the therapeutic regimen included
      quetiapine XR. Data were reported descriptively. This analysis included 811
      patients. Psychiatric histories indicated a burden of severe MDD in these
      patients. Patient demographics were similar across countries; however, those in
      Sweden had a younger mean age. Physicians' ratings of the therapeutic effect of
      prior treatment with antidepressants suggested the need for an add-on treatment
      for most patients. Overall, 15.7% of patients initiated quetiapine XR treatment
      as monotherapy. Presence of psychotic symptoms during depressive episodes
      predicted treatment with higher than recommended doses of quetiapine XR (odds
      ratio=3.11; 95% confidence interval: 1.6-6.0). This analysis demonstrated
      similarities in DU across the countries analyzed, largely in accordance with the
      recommended dose of quetiapine XR as an adjunctive therapy to antidepressants in
      MDD (50-300 mg/day).

PMID- 29068795
TI  - The role of renal response to amino acid infusion and oral protein load in normal
      kidneys and kidney with acute and chronic disease.
AB  - PURPOSE OF REVIEW: High protein intake and hyperfiltration have been a focus of
      major interest as potential mechanism(s) of progression of renal disease. This
      review will examine: the renal response to a protein meal or amino acid infusion
      and its use to test the renal functional reserve (RFR); new methods to evaluate
      RFR; the use of RFR in various pathophysiologic conditions. RECENT FINDINGS: The
      renal response to protein/amino acid infusion involves several mechanisms,
      including nitric oxide, insulin, glucagon, arginine vasopressin, urea, the renal
      N-Methyl-D-Aspartate Glutamate receptor and modulation of the activity of the
      tubuloglomerular feedback system. Dose-response studies to evaluate RFR suggest
      the presence of a potential ceiling. The utilization of a noninvasive technique
      such as Doppler ultrasonography is trying to simplify the measurement of RFR and
      to bring this test into different clinical settings. There is increased interest
      in the presence or absence of RFR in patients with acute kidney injury,
      hypertension, chronic kidney disease, and its potential long-term implication
      regarding renal function. SUMMARY: The renal response to protein may help us
      understand the relationship between hyperfiltration, progression of renal
      disease, and other conditions (overall mortality, cardiovascular complications,
      and so on) currently being explored.

PMID- 29068793
TI  - Use of fast-scan cyclic voltammetry to assess phasic dopamine release in rat
      models of early postpartum maternal behavior and neglect.
AB  - Maternal behavior (MB) is a complex response to infant cues, orchestrated by
      postpartum neurophysiology. Although mesolimbic dopamine contributes toward MB,
      little is known about real-time dopamine fluctuations during the postpartum
      period. Thus, we used fast-scan cyclic voltammetry to measure individual dopamine
      transients in the nucleus accumbens of early postpartum rats and compared them
      with dopamine transients in virgins and in postpartum females exposed to cocaine
      during pregnancy, which is known to disrupt MB. We hypothesized that dopamine
      transients are normally enhanced postpartum and support MB. In anesthetized rats,
      electrically evoked dopamine release was larger and clearance was faster in
      postpartum females than in virgins and gestational cocaine exposure blocked the
      change in clearance. In awake rats, control mothers showed more dopamine
      transients than cocaine-exposed mothers during MB. Salient pup-produced stimuli
      may contribute toward differences in maternal phasic dopamine by evoking dopamine
      transients; supporting the feasibility of this hypothesis, urine composition
      (glucose, ketones, and leukocytes) differed between unexposed and cocaine-exposed
      infants. These data, resulting from the novel application of fast-scan cyclic
      voltammetry to models of MB, support the hypothesis that phasic dopamine
      signaling is enhanced postpartum. Future studies with additional controls can
      delineate which aspects of gestational cocaine reduce dopamine clearance and
      transient frequency.

PMID- 29068796
TI  - Protein phosphatases and podocyte function.
AB  - PURPOSE OF REVIEW: Deregulation of protecting factor signaling actions in
      podocytes has emerged as an alternative pathway of podocyte injury mechanisms.
      Here, we review recent knowledge that highlighted how podocyte protecting factors
      are modulated by protein phosphatases. RECENT FINDINGS: Protein tyrosine kinases
      and phosphatases participate in many, if not all, aspects of cellular function by
      turning on or off multiple signaling cascades and podocytes are no exception.
      Modulation of tyrosine residue phosphorylation of podocyte factors such as
      nephrin, vascular endothelial growth factor, insulin receptors and substrates has
      been shown to promote podocyte damage and cell death that contributed to multiple
      glomerular diseases. Protein phosphatase activity can cause either an increase
      [Src homology 2 domain-containing phosphatase 2 (SHP-2)] or a decrease [Protein
      tyrosine phosphatase1B (PTP1B), SHP-1 and SH2 domain-containing 5'-inositol
      phosphatase 2 (SHIP2)] in nephrin tyrosine phosphorylation depending on which
      podocyte injury model was used. Insulin resistance is closely linked to the
      development and progression of renal disease. Expression of PTP1B, SHP-1,
      phosphatase and tensin homolog and SHIP2 are potential mechanisms of podocytes
      insulin resistance in diabetic kidney disease. SUMMARY: Tight regulation of
      protein phosphatases is critical to maintain cell homeostasis and may offer new
      perceptive targets to restore protecting factor actions in order to prevent
      podocyte dysfunction and glomerular diseases.

PMID- 29068797
TI  - Alanine aminotransferase blood levels and rehabilitation outcome in older adults
      following hip fracture surgery.
AB  - Low alanine aminotransferase (ALT) blood levels are associated with frailty and
      poor outcome in older adults. Therefore, we studied the association between ALT
      blood levels before rehabilitation and rehabilitation outcome in older adults
      following hip fracture surgery. A total of 490 older adults (age>60 years, mean
      age: 82.9+/-6.7 years, 82.0% women) admitted to rehabilitation following hip
      fracture surgery were included. The rehabilitation outcome was assessed by
      Functional Independence Measure (FIM) scores. ALT blood levels were documented
      between 1 and 6 months before rehabilitation. Patients with ALT blood levels over
      40 IU/l possibly consistent with liver injury were excluded. The cohort was
      divided into two groups: patients with ALT more than 10 IU/l and patients with
      ALT less than or equal to 10 IU/l. Upon rehabilitation discharge, the FIM outcome
      measures (motor, cognitive, gain, efficiency) were significantly higher in
      patients with ALT more than 10 IU/l relative to patients with ALT less than or
      equal to 10 IU/l (P<0.05). A logistic regression analysis adjusted for age and
      sex showed that patients with ALT more than 10 IU/l were more likely to have
      higher (second to fourth upper quartiles) total FIM scores (>50), cognitive FIM
      scores (>16), and FIM efficiency (>0.228) upon rehabilitation discharge (odds
      ratio=1.56-1.78). However, this association was no longer significant following
      adjustment also for admission total FIM score, cognitive impairment, cancer, and
      albumin serum levels. High-normal ALT blood levels before rehabilitation are
      associated with a better rehabilitation outcome in older adults following hip
      fracture surgery. It may be used when data on admission FIM score, cognitive
      impairment, cancer, and albumin serum levels are not available.

PMID- 29068798
TI  - Use of pain medication before and after inpatient musculoskeletal rehabilitation:
      longitudinal analysis of a nationwide cohort.
AB  - The objective of this study was to identify subgroups among the participants in
      inpatient multidisciplinary musculoskeletal rehabilitation based on the
      differences in the shapes of trajectories of pain medication consumption during
      the 9 years around the time of intervention. A register-based study among 4578
      public sector employees was conducted. Group-based trajectory analysis was done
      on the purchase of prescribed pain medications during the 9 years around the time
      of rehabilitation. The participants were on an average 50.7 (SD=6.6) years of
      age, and 2955 (86%) were women. Average yearly purchase of pain medications
      increased during the follow-up period from 73.4 (SD=193.0) to 163.3 (SD=295.7)
      defined daily doses. The analysis suggested six-cluster model. The shapes of the
      trajectories of three clusters did not show any steep slopes, one trajectory
      demonstrated nonstop rising through the entire follow-up, and one trajectory was
      closed to the trajectory average of medication use. One trajectory (11% of the
      sample) demonstrated a steep growth before the intervention and steep drop after
      it. When comparing this cluster with all other clusters combined, odds ratios
      were 0.40 [95% confidence interval (CI): 0.19-0.85] for age group (older vs.
      younger), 0.78 (95% CI: 0.61-1.01) for sex (women vs. men), and 1.44 (95% CI:
      1.09-1.90) for occupational status (lower vs. higher). In other words, the
      participants belonged to this cluster were younger employees with a lower
      occupational grade. It seems that younger employees in manual jobs benefitted of
      the studied multidisciplinary musculoskeletal rehabilitation the most, especially
      when the timing of intervention is bounded to the substantial rise of pain
      severity.

PMID- 29068799
TI  - Comparative Study on Early Osseointegration of Implants According to Various
      Drilling Speeds in the Mandible of Dogs.
AB  - PURPOSE: This study evaluated the effect of drilling speed on early bone healing
      in the mandible of dogs. MATERIAL AND METHODS: Six dogs were selected, and
      mandibular premolars and molars were extracted. After 2 months, 3 hydroxyapatite
      surfaced fixtures were implanted with drilling speeds of 50, 800, and 1200 rpm on
      the right side first and then on the left side after 2 weeks. Implant stability
      quotient (ISQ) was measured on insertion, after 2 and 4 weeks. RESULTS: Based on
      the ISQ measurement, the 1200-rpm group showed a higher value than the 50-rpm
      group at 2 weeks and 4 weeks (P < 0.05). New bone formation around the implant
      was highest for the 800-rpm group at 2 weeks and the 1200-rpm group at 4 weeks.
      The bone-implant contact of the superior half of the alveolar bone was highest
      for the 800-rpm group at 2 weeks and the 1200-rpm group at 4 weeks. There was no
      statistically significant difference. CONCLUSION: This study suggests that 50,
      800, and 1200 rpm are drilling speeds which can expect favorable outcome, yet,
      higher drilling speed presented overall the best biological responses.

PMID- 29068800
TI  - The Impact of Positive Resection Margins on Survival and Recurrence Following
      Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma.
AB  - OBJECTIVE AND BACKGROUND: Local and distant disease recurrence are frequently
      observed following pancreatic cancer resection, but an improved understanding of
      resection margin assessment is required to aid tailored therapies. METHODS:
      Analyses were carried out to assess the association between clinical
      characteristics and margin involvement as well as the effects of individual
      margin involvement on site of recurrence and overall and recurrence-free survival
      using individual patient data from the European Study Group for Pancreatic Cancer
      (ESPAC)-3 randomized controlled trial. RESULTS: There were 1151 patients, of whom
      505 (43.9%) had an R1 resection. The median and 95% confidence interval (CI)
      overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with
      resection margin negative (R0 >1 mm) tumors, 25.4 (21.6-30.4) months for 146
      (12.7%) patients with R1<1 mm positive resection margins, and 18.7 (17.2-21.1)
      months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In
      multivariable analysis, overall R1-direct tumor margins, poor tumor
      differentiation, positive lymph node status, WHO performance status >=1, maximum
      tumor size, and R1-direct posterior resection margin were all independently
      significantly associated with reduced overall and recurrence-free survival.
      Competing risks analysis showed that overall R1-direct positive resection margin
      status, positive lymph node status, WHO performance status 1, and R1-direct
      positive superior mesenteric/medial margin resection status were all
      significantly associated with local recurrence. CONCLUSIONS: R1-direct resections
      were associated with significantly reduced overall and recurrence-free survival
      following pancreatic cancer resection. Resection margin involvement was also
      associated with an increased risk for local recurrence.

PMID- 29068801
TI  - Anal Sphincter Anatomy Prepregnancy to Postdelivery Among the Same Primiparous
      Women on Dynamic Magnetic Resonance Imaging.
AB  - OBJECTIVES: The authors used 2-dimensional images from pelvic 3 T magnetic
      resonance imaging (MRI) to characterize changes in the internal anal sphincter
      (IAS) and external anal sphincter (EAS) from prepregnancy to postdelivery in the
      same cohort. METHODS: This secondary analysis studied a prospective cohort of
      women undergoing 3 T MRI before their first pregnancy and 6 or more months after
      delivery. Radial thickness was measured at 12, 3, 9, and 6 o'clock from axial
      proximal and mid views and oblique distal views of the IAS, and at 3 and 9
      o'clock from oblique views of the EAS. Measurements were compared prepregnancy to
      postdelivery; 10 women had 80% power (alpha = 0.05) to detect a 0.85-mm change.
      RESULTS: Nineteen women completed initial 3 T MRI, 15 achieved pregnancy and
      birth, and 10 completed postdelivery MRI (4 vaginal birth and 6 Cesarean
      delivery). Mean change in measurement from prepregnancy to postdelivery was -0.01
      mm +/- 1.03 mm for the distal 12 o'clock IAS (P = 0.98) and +0.19 +/- 0.64 mm for
      the lateral EAS (P = 0.32). All prepregnancy and postdelivery women had
      discontinuous EA sphincters at 6 and 12 o'clock. There were no statistically
      significant changes from prepregnancy to postdelivery in any IAS or EAS location
      (all >0.05) for the entire cohort, those with vaginal birth, or after Cesarean.
      CONCLUSIONS: Anal sphincter measurements on MRI did not change significantly in
      nulliparous women prepregnancy to postdelivery at any location, and the EAS was
      not measurable at 12 o'clock in any women at either time point, challenging
      classic concepts of EAS anatomy.

PMID- 29068802
TI  - Emergency Ventilation of Infant Subglottic Stenosis Through Small-Gauge Lumen
      Using the Ventrain: A Case Report.
AB  - Postintubation subglottic stenosis is one of the most common causes of stridor in
      newborns and babies after prolonged mechanical ventilation. Management of this
      pathology is complex and requires highly trained personnel because it is
      associated with a high rate of airway-related mortality. This article presents
      the rescue of a difficult airway in a pediatric patient with subglottic stenosis
      with a new device available on the market, the Ventrain, offering certain
      advantages over those available until now.

PMID- 29068803
TI  - Anaphylaxis to Surgiflo During Posterior Spinal Fusion in an Adolescent Status
      Post Truncus Arteriosus Repair: A Case Report.
AB  - Anaphylactic reaction to gelatin-containing hemostatic agents has been reported
      in the orthopedic literature, most commonly during scoliosis repair in
      adolescents. However, the risk, differential diagnosis, and management of
      anaphylaxis in patients with complex congenital heart disease undergoing
      noncardiac procedures have not been previously reported. We describe the case of
      an adolescent with a history of repaired truncus arteriosus undergoing posterior
      spinal fusion who developed sudden and profound hypotension that was ultimately
      confirmed to be an anaphylactic reaction to Surgiflo. Echocardiography was used
      to aid in diagnosis and management of the cardiovascular effects of anaphylaxis
      in this patient with residual cardiac pathophysiology.

PMID- 29068804
TI  - Low-energy cardiac shockwave therapy to suppress left ventricular remodeling in
      patients with acute myocardial infarction: a first-in-human study.
AB  - OBJECTIVE: Although primary percutaneous coronary intervention (PCI)
      substantially reduces the mortality of patients with acute myocardial infarction
      (AMI), left ventricular (LV) remodeling after AMI still remains an important
      issue in cardiovascular medicine. We have previously demonstrated that low-energy
      cardiac shockwave (SW) therapy ameliorates LV remodeling after AMI in pigs. In
      this first-in-human study, we examined the feasibility and the effects of the SW
      therapy on LV remodeling after AMI in humans. PATIENTS AND METHODS: Seventeen
      patients with AMI who successfully underwent primary PCI (peak-creatine
      kinase<4000 U/l) were treated with the SW therapy. Low-energy shock waves were
      applied to the ischemic border zone around the infarcted area at 2, 4, and 6 days
      since AMI. Next, we compared these patients with historical AMI controls by
      propensity score matching (N=25). RESULTS: There were no procedure-related
      complications or adverse effects. At 6 and 12 months after AMI, LV function as
      assessed by MRI showed no signs of deleterious LV remodeling. When we compared
      the SW-treated group with the historical AMI controls at 6 months after AMI, LV
      ejection fraction was significantly higher in the SW-treated group (N=7) than in
      the historical control group (N=25) by echocardiography (66+/-7 vs. 58+/-12%,
      P<0.05). LV end-diastolic dimension also tended to be smaller in the SW than in
      the control group (47.5+/-4.6 vs. 50.0+/-5.9 mm, P=0.29). CONCLUSION: These
      results suggest that low-energy extracorporeal cardiac SW therapy is feasible and
      may ameliorate postmyocardial infarction LV remodeling in patients with AMI as an
      adjunctive therapy to primary PCI.

PMID- 29068805
TI  - Outcomes of Preoperative Versus Postoperative Radiation for Heterotopic
      Ossification Prevention in Children With Neuromuscular Hip Dysplasia Undergoing
      Proximal Femoral Resection.
AB  - BACKGROUND: Few studies exist to inform the extrapolated practice of irradiating
      children for heterotopic ossification (HO) prevention. We report the incidence of
      HO formation following prophylactic preoperative compared with postoperative
      radiation therapy (RT) in children with neuromuscular hip dysplasia (NHD)
      following proximal femoral resection (PFR). METHODS: A retrospective, 2
      institution chart review was performed. Eligibility was limited to patients with
      at least 1 year of follow-up. Evaluation included radiographic HO grading by a
      combined severity scale, assessment of synchronous symptoms of pain or decreased
      range of motion, and stratification by preoperative versus postoperative
      reception of RT. A control cohort included 4 nonirradiated hips with NHD after
      PFR. RESULTS: Twenty-five hips in 20 children met eligibility criteria. Eleven
      hips were irradiated preoperatively and 14 postoperatively. Radiographic evidence
      of post-RT development of radiographic evidence of heterotopic ossification (rHO)
      was found in all 25 hips and earlier in patients irradiated preoperatively
      (median time to rHO was 4.0 vs. 15.7 mo, P=0.03, 95% confidence interval, 0.24
      21.5). There was no statistically significant difference in the development of
      symptomatic HO (P=0.62) between the preoperative (45.5%) and postoperative
      (35.7%) groups, nor in HO grade (P=0.34). Seven (28%) of the 25 hips (5
      preoperative and 2 postoperative) had documentation of rHO-free intervals after
      surgery, with an average duration of 5.6 months, while the remaining presented
      with rHO at first follow-up visit. All eligible control hips (100%) developed rHO
      and symptomatic heterotopic ossification. CONCLUSIONS: Perioperative RT did not
      prevent the formation of HO in any child with NHD after PFR. Extrapolation of
      evidence of the efficacy of RT for HO prevention in ambulatory adults after
      traumatic hip injury to a population of children with central nervous system
      injury and NHD may be premature. Additional studies are needed to clarify optimal
      prevention of HO in this population. LEVEL OF EVIDENCE: Level III-therapeutic
      retrospective comparative study.

PMID- 29068806
TI  - Innovation and Entrepreneurship: Harnessing the Public Health Skill Set in a New
      Era of Health Reforms and Investment.

PMID- 29068807
TI  - Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of
      Acutely Induced Atrial Fibrillation in Horses.
AB  - BACKGROUND: Antiarrhythmic compounds against atrial fibrillation (AF) often have
      reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can
      be improved by combining 2 compounds with distinct mechanisms, and it may be
      possible to use lower doses of each compound, thereby reducing the likelihood of
      adverse side effects. The purpose of this study was to investigate whether the
      effective doses of dofetilide and ranolazine can be reduced if the drugs are
      combined. METHODS: Dofetilide, ranolazine, and a combination of these were
      administered in 4 incremental dosing regimens to horses with acutely pacing
      induced AF. Time to cardioversion, atrial effective refractory period, and AF
      vulnerability and duration were assessed. RESULTS: Of 8 horses, 6 cardioverted to
      sinus rhythm after infusion with a combination of 0.889 MUg/kg dofetilide and
      0.104 mg/kg ranolazine. Two horses cardioverted with 0.104 mg/kg ranolazine
      alone, and 3 cardioverted with 0.889 MUg/kg dofetilide alone. The combination
      therapy decreased AF vulnerability (P < 0.05) and AF duration (P < 0.05). No
      change in atrial effective refractory period was detected with any of the drugs.
      CONCLUSIONS: The combination of dofetilide and ranolazine showed increased
      antiarrhythmic effects on acutely induced AF in horses, affecting time to
      cardioversion, AF vulnerability, and AF duration.

PMID- 29068810
TI  - Rhabdomyolysis: a 10-year retrospective study of patients treated in a medical
      department.
AB  - BACKGROUND: Rhabdomyolysis is a common and potentially life-threatening syndrome,
      and acute kidney injury (AKI) is a serious complication. We performed a 10-year
      retrospective study that included all patients treated for rhabdomyolysis in a
      medical clinic. We examined the relationships between the levels of creatine
      kinase (CK), myoglobin, and creatinine (as a marker of renal function and thereby
      AKI), and whether the myoglobin/CK ratio could be a valuable tool in the clinical
      evaluation of this patient group. Clinical characteristics were noted. PATIENTS
      AND METHODS: The study included all patients treated for rhabdomyolysis in the
      Department of Medicine, Oslo University Hospital Ulleval, from 2003 to 2012.
      Rhabdomyolysis was defined as a serum CK activity more than five times the upper
      reference limit. RESULTS: A total of 341 patients were included in the study; 51%
      developed AKI, and 20% of those required dialysis. Logistic regression showed
      that myoglobin concentration [P<0.001, odds ratio (OR)=6.24] was a better
      predictor than CK activity (P=0.001, OR=3.45) of the development of AKI. The
      myoglobin/CK ratio was a good predictor of AKI (P<0.001, OR=5.97). The risk of
      developing AKI increased with increasing myoglobin/CK ratio (P<0.001); a ratio
      more than 0.2 was associated with an increased likelihood of developing AKI.
      CONCLUSION: Serum myoglobin concentration was a better predictor of AKI than was
      serum CK activity. The myoglobin/CK ratio may be useful for assessing the
      likelihood of developing AKI.

PMID- 29068809
TI  - Advances in managing and preventing thromboembolic disease in cancer patients.
AB  - PURPOSE OF REVIEW: To update on new data for low-molecular weight heparins
      (LMWHs) and the direct oral anticoagulants (DOACs) for the treatment and
      prevention of cancer-associated thrombosis (CAT), to discuss progress with the
      risk-adaptive management scores (RAMS) and update on increased dose primary
      thromboprophylaxis (IDPTP). RECENT FINDINGS: In a pooled meta-analysis of 1132
      cancer patients who received DOACs vs. vitamin K analogues (VKAs), recurrence of
      venous thromboembolism (VTE) was reduced from 6.0% on VKA schedules to 3.9% on
      DOACs. In a randomized trial of warfarin vs. once daily sc. tinzaparin (175
      IU/kg), cumulative 6-month VTE incidence reduced from 10.5 to 7.2% [hazard ratio,
      0.65 (95% confidence interval, 0.41-1.03); P = 0.07]. Despite early suggestions
      that DOACs may have a role in CAT, 3-6 months of LMWH remain the standard for
      initial treatment of CAT. A prospective comparison of RAMS found the Vienna CATS
      or the PROTECHT scores superior to the Khorana score but concluded that RAMS did
      not perform well enough to be used in the clinic. An efficacy scale of LMWHs in
      pancreatic cancer facilitates IDPTP. Practical implementation of IDPTP was needed
      to control the 40% VTE incidence of the HALO-109-202 study in metastatic
      pancreatic cancer. SUMMARY: DOACs have some encouraging data, but LMWHs remain
      the standard for CAT treatment. RAMS generated to predict VTE occurrence or
      recurrence are still of unproven significance and IDPTP for advanced pancreatic
      cancer has tools and guidance for implementation.

PMID- 29068811
TI  - Forensic Features of Clothing-Related Deaths: Historical and Cultural Aspects.
AB  - Clothing may both cause death and contribute to ongoing lethal mechanisms by a
      variety of quite disparate mechanisms. The manner of death may be accidental,
      suicidal, or homicidal. Accidental deaths include burning from clothing catching
      on fire, strangulation from clothing tangling in vehicle wheels or exposed
      machinery, and drowning. Entanglement of clothing in machinery may also result in
      significant injuries, which are not uncommon in farming communities. Excessive
      clothing, or its absence, may significantly alter body temperature, and hanging
      from clothing is a feature in the young or in mentally or physically handicapped
      adults, or in adults who are intoxicated with alcohol or drugs. In previous
      years, potentially lethal amounts of arsenic were present in clothing and
      accessories from dyes. Clothing may also be used to form nooses or to pad ropes
      in suicides and may be used in cases of strangulation, suffocation, or choking in
      homicides. The contribution of clothing to mortality has changed over the years
      with changes in fashions and in manufacturing techniques. Geographical
      differences in clothing-related deaths persist because of variable social and
      cultural practices and legislative frameworks.

PMID- 29068812
TI  - Intra-Abdominal Hemorrhage Complicating Electrothermal Arterial Injury During
      Pelvic Surgery: A Case Report.
AB  - Iatrogenic vascular injury is a potentially serious complication of surgical
      procedures. Here we report a case of delayed fatal intra-abdominal hemorrhage
      because of electrocautery injury of a right external iliac artery. The decedent,
      a 31-year-old woman, died suddenly on postoperative day 1 after a laparoscopic
      staging operation for an ovarian tumor. Her past medical history included a
      recent diagnosis of a microinvasive carcinoma in the background of a mucinous
      cystic neoplasm of the right ovary. Postmortem examination revealed a young woman
      with evidence of emergency intervention, recent laparoscopic pelvic surgery, and
      pale hypostasis limited to the back surfaces of the body. The internal
      examination confirmed the postmortem computed tomography findings of a large
      amount of blood in the pelvic and abdominal cavities and evidence of recent
      surgical intervention. The soft tissues around the aorta and major pelvic vessels
      showed electrocautery change and marked perivascular hemorrhage preferentially
      surrounding the right external iliac artery. Histological examination of the
      vascular bundle showed an electrocautery injury of the arterial wall: transmural
      necrosis, acute inflammation, and hemorrhage. In this report, we offer an
      approach to a postmortem examination in postoperative deaths with emphasis on
      deaths due to iatrogenic vascular injuries and discuss the rationale for
      determining the manner of death.

PMID- 29068813
TI  - The Shared Goals and Distinct Strengths of the Medical Humanities: Can the Sum of
      the Parts Be Greater Than the Whole?
AB  - Since the 1960s, faculty from diverse fields have banded together under the
      banner of the medical humanities, a term which unites art, literature, history,
      anthropology, religious studies, philosophy, and other disciplines. Arguments for
      the relevance of medical humanities often emphasize contributions that any of
      these disciplines can make to medical education, whether those involve empathy,
      professionalism, critical reasoning, or tolerating ambiguity. The authors argue
      that the constituent disciplines of the medical humanities are not
      interchangeable parts, but represent different perspectives and methodologies
      that offer their own distinct contributions to medical training. Efforts to
      define a role for medical humanities in medical education should pursue two
      strategies in parallel. On the one hand, advocates of the medical humanities
      should continue to make the case for the shared contributions that all of the
      disciplines can make to medical education. But advocates for the medical
      humanities should also emphasize the valuable contributions of each specific
      discipline, in terms that medical educators can understand. The authors
      illustrate this point by delineating contributions of their own discipline,
      medical history. Historical analysis contributes essential insights to the
      understanding of disease, therapeutics, and institutions-things that all
      physicians must know in order to be effective as clinicians, just as they must
      learn anatomy or pathophysiology. Analogous but different arguments can be made
      for literature, philosophy, and the other disciplines that constitute the medical
      humanities. The field of medical humanities will be most successful if it builds
      on both the shared and the distinct contributions of its disciplines.

PMID- 29068815
TI  - How Effective Leaders Harness the Future.
AB  - Human beings are fundamentally future oriented. Most of our decisions and
      undertakings are for the sake of a future to which we are committed or obligated.
      This future orientation is essential to effective leadership in health care,
      especially during this time of significant reform, when people are at risk of
      becoming cynical and disengaged. Conventional thinking holds that our
      effectiveness as leaders is primarily a function of what we have learned in the
      past-our knowledge, expertise, and experience. In contrast, the emerging model
      contends that our effectiveness is also a function of how the future (outcome) of
      our leadership challenges "shows up" for us. If, despite daunting circumstances,
      we can "see" an aspired future ahead, we are more likely to commit and engage.
      Our story of the future becomes the "narrative frame" through which we see and
      tackle leadership challenges today. Because organizations are fundamentally
      networks of conversations, an organization's ability to create new language
      practices is tantamount to its ability to evolve. What makes the future
      compelling is the embodiment of our deepest convictions and ideals in our image
      of the future. Because health care reform has challenged the medical profession
      along the entire spectrum of its traditional values and roles, working toward a
      unifying vision of the future has been difficult. To enroll others in creating a
      better future, effective leaders must underscore the purpose and importance of
      their work and motivate them with inspiring stories.

PMID- 29068814
TI  - The "Glocalization" of Medical School Accreditation: Case Studies From Taiwan,
      South Korea, and Japan.
AB  - PURPOSE: In an age of globalized medical education, medical school accreditation
      has been hailed as an approach to external quality assurance. However,
      accreditation standards can vary widely across national contexts. To achieve
      recognition by the World Federation for Medical Education (WFME), national
      accrediting bodies must develop standards suitable for both local contexts and
      international recognition. This study framed this issue in terms of
      "glocalization" and aimed to shine light on this complicated multistakeholder
      process by exploring accreditation in Taiwan, South Korea, and Japan. METHOD:
      This study employed a comparative case-study design, examining the national
      standards that three accreditation bodies in East Asia developed using
      international reference standards. In 2015-2016, the authors conducted document
      analysis of the English versions of the standards to identify the differences
      between the national and international reference standards as well as how and why
      external standards were adapted. RESULTS: Each country's accreditation body
      sought to balance local needs with global demands. Each used external standards
      as a template (e.g., Liaison Committee on Medical Education, General Medical
      Council, or WFME standards) and either revised (Taiwan, South Korea) or annotated
      (Japan) the standards to fit the local context. Four categories of differences
      emerged to account for how and why national standards departed from external
      references: structural, regulatory, developmental, and aspirational. CONCLUSIONS:
      These countries' glocalization of medical accreditation standards serve as
      examples for others seeking to bring their accreditation practices in line with
      global standards while ensuring that local values and societal needs are given
      adequate consideration.

PMID- 29068816
TI  - Concerns and Responses for Integrating Health Systems Science Into Medical
      Education.
AB  - With the aim of improving the health of individuals and populations, medical
      schools are transforming curricula to ensure physician competence encompasses
      health systems science (HSS), which includes population health, health policy,
      high-value care, interprofessional teamwork, leadership, quality improvement, and
      patient safety. Large-scale, meaningful integration remains limited, however, and
      a major challenge in HSS curricular transformation efforts relates to the
      receptivity and engagement of students, educators, clinicians, scientists, and
      health system leaders. The authors identify several widely perceived challenges
      to integrating HSS into medical school curricula, respond to each concern, and
      provide potential strategies to address these concerns, based on their
      experiences designing and integrating HSS curricula. They identify two broad
      categories of concerns: the (1) relevance and importance of learning HSS
      including the perception that there is inadequate urgency for change; HSS
      education is too complex and should occur in later years; early students would
      not be able to contribute, and the roles already exist; and the science is too
      nascent-and (2) logistics and practicality of teaching HSS-including limited
      curricular time, scarcity of faculty educators with expertise, lack of support
      from accreditation agencies and licensing boards, and unpreparedness of evolving
      health care systems to partner with schools with HSS curricula. The authors
      recommend the initiation and continuation of discussions between educators,
      clinicians, basic science faculty, health system leaders, and accrediting and
      regulatory bodies about the goals and priorities of medical education, as well as
      about the need to collaborate on new methods of education to reach these goals.

PMID- 29068817
TI  - Broadening the Scope of Feedback to Promote Its Relevance to Workplace Learning.
AB  - The common goal in medical education is to support the health care workforce,
      both present and future, in becoming and remaining competent professionals. Both
      during and after medical training, learning takes place in the clinical
      workplace. Yet, how feedback is defined in medical education and how it is
      practiced in clinical training situations, combined with a research focus on
      "what works," limits its potential for learning. This article explores the
      theoretical background of learning in interaction and current trends in medical
      education to broaden the scope of feedback and promote its relevance to workplace
      learning.A new, wider perspective is outlined in which feedback could be
      redefined as "performance-relevant information" (PRI). PRI can incorporate all
      information that is deemed relevant to the learner, drawn from interaction in
      workplace learning and one's interpretation of performance in the clinical
      workplace. This information can, for example, come from the evaluation of patient
      outcomes after treatment; observations of role models' performance; evaluations
      and assessments; exploring feelings of failure or success; and responses of
      colleagues and peers.PRI draws attention to learning opportunities that better
      fit the highly social learning of clinical workplaces and current trends in
      medical education. It supports the interpretation of individual or team
      performance in terms of relevance to learning. This allows for a comprehensive
      way of viewing and stimulating workplace learning and the performance of
      professionals, providing an opportunity to create lifelong learning strategies
      and potentially improving the care of patients.

PMID- 29068818
TI  - Simulation-Based Mastery Learning for Thoracentesis Skills Improves Patient
      Outcomes: A Randomized Trial.
AB  - PURPOSE: Physicians-in-training often perform bedside thoracenteses in academic
      medical centers, and complications are more common among less experienced
      clinicians. Simulation-based mastery learning (SBML) is one potential solution to
      this problem. This study evaluated the effects of a randomized trial of
      thoracentesis SBML on patient complications: iatrogenic pneumothorax (IP),
      hemothorax, and reexpansion pulmonary edema (REPE). METHOD: The authors
      randomized internal medicine residents to undergo thoracentesis SBML at a
      tertiary care academic center from December 2012 to May 2016. They subsequently
      compared thoracentesis complications from procedures performed by SBML-trained
      residents, traditionally trained residents (no simulation training), and those
      referred to pulmonary medicine or interventional radiology (IR). RESULTS: During
      the study period, 917 thoracenteses were performed on 709 patients. IP occurred
      in 60 (6.5%) procedures, of which 7 (11.6%) were clinically meaningful. SBML
      trained residents performed procedures with a trend toward lower combined
      clinically meaningful complications (IP, hemothorax, REPE) compared with
      traditionally trained residents (7.9% vs. 0%; P = .06). SBML-trained residents
      caused fewer clinically meaningful IPs compared with traditionally trained
      residents, pulmonary, and IR referrals (P = .02). Hemothorax occurred after 4
      (0.4%) thoracenteses, and SBML-trained residents had a trend toward lower
      hemothorax (0) compared with other groups (P = .07). REPE occurred after 3 (0.3%)
      procedures, with no differences between groups. SBML-trained residents performed
      procedures with lower combined clinically meaningful complications compared with
      other groups (P = .008). CONCLUSIONS: Residents randomized to an SBML
      intervention performed thoracenteses with low rates of clinically meaningful
      complications. Rigorous education represents a successful quality improvement
      strategy.

PMID- 29068819
TI  - An Innovative Shared Decision-Making Curriculum for Internal Medicine Residents:
      Findings From the University of Pittsburgh Medical Center.
AB  - PURPOSE: Shared decision making (SDM) is a core competency in health policy and
      guidelines. Most U.S. internal medicine residencies lack an SDM education
      curriculum. A standardized patient (SP)-based curriculum teaching key concepts
      and skills of SDM was developed. METHOD: This curriculum consisted of an
      innovative seven-step SDM model and a skills-focused SP case, integrated into the
      ambulatory rotation for senior medicine residents at the University of Pittsburgh
      Medical Center in 2015. Evaluation consisted of pre/postcurriculum surveys
      assessing residents' knowledge of and attitudes toward SDM. Skills development
      was assessed via pre/postcurricular audio recordings of clinical decision making.
      RESULTS: Thirty-six residents completed the curriculum (survey participation rate
      88%). There was significant improvement in residents' knowledge (median score pre
      75%, post 100%, P < .01); confidence (median composite score pre 2.87, post 3.0,
      P < .01, where 1 = not confident/important, 4 = very confident/important); and
      importance of SDM (median composite score pre 3.14, post 3.5, P < .01). Forty
      four clinical recordings (31 pre, 13 post) were assessed using the Observing
      Patient Involvement in Decision-Making scale. Improvement in use of SDM skills
      was seen among all residents (mean increase 1.84 points, P = .27). When data were
      stratified post hoc by U.S. versus international medical graduates, there was
      significant improvement in total score (mean increase of 5.15 points, P = .01)
      among U.S. graduates only. CONCLUSIONS: SDM is teachable, and this skill-based
      curricular intervention resulted in improvement in senior medicine residents'
      knowledge of, attitudes toward, and demonstration of SDM skills.

PMID- 29068821
TI  - Who Am I, and Who Do I Strive to Be? Applying a Theory of Self-Conscious Emotions
      to Medical Education.
AB  - The self-conscious emotions of shame, guilt, and pride are a distinct set of
      cognitively complex, powerful, and ubiquitous emotions that arise when an
      individual engages in self-evaluation. Currently, little is known about the
      influence or outcomes of self-conscious emotions in medical learners. In this
      article, the authors present a leading theory of self-conscious emotions that
      outlines the appraisals and attributions that give rise to and differentiate
      shame, guilt, and two forms of pride. The authors then apply the theory to three
      relevant topics in medical education: perfectionism, professional identity
      formation, and motivation. In doing so, the authors present novel ways of viewing
      these topics through the lens of self-conscious emotion, suggest areas of future
      research, and outline a framework for emotional resilience training. Ultimately,
      the goal of this article is to highlight the fundamental nature of shame, guilt,
      and pride, which the authors believe are underappreciated and understudied in
      medical education, and to inform future empirical study on the role that these
      emotions might play in medical education. Additionally, from a practical
      standpoint, this article aims to encourage educators and learners to recognize
      self-conscious emotions in themselves and their colleagues, and to begin
      developing more resilient approaches to learning-approaches that acknowledge and
      confront shame, guilt, and pride in medical education.

PMID- 29068822
TI  - Dilemmas of Representation: Patient Engagement in Health Professions Education.
AB  - The role of the patient in bedside teaching has long been a matter of
      consideration in health professions education. Recent iterations of patient
      engagement include patients as storytellers, members of curriculum planning
      committees, guest lecturers, and health mentors. While these forms of patient
      engagement are reported to have many benefits for learners, educators, and the
      patients themselves, there is concern that such programs may not be
      representative of the diversity of patients that health care professionals will
      encounter throughout their careers. This problem of representation has vexed not
      only educators but also sociologists and political scientists studying patients'
      and the public's involvement in arenas such as health services research, policy,
      and organizational design.In this Perspective, the authors build on these
      sociological and political science approaches to expand our understanding of the
      problem of representation in patient engage-ment. In doing so, the authors'
      reconfiguration of the problem sheds new light on the dilemma of representation.
      They argue for an understanding of representation that not only is inclusive of
      who is being represented but that also takes seriously what is being represented,
      how, and why. This argument has implications for educators, learners,
      administrators, and patient participants.

PMID- 29068820
TI  - Race/Ethnicity and Success in Academic Medicine: Findings From a Longitudinal
      Multi-Institutional Study.
AB  - PURPOSE: To understand differences in productivity, advancement, retention,
      satisfaction, and compensation comparing underrepresented medical (URM) faculty
      with other faculty at multiple institutions. METHOD: A 17-year follow-up was
      conducted of the National Faculty Survey, a random sample from 24 U.S. medical
      schools, oversampled for URM faculty. The authors examined academic productivity,
      advancement, retention, satisfaction, and compensation, comparing white, URM, and
      non-URM faculty. Retention, productivity, and advancement data were obtained from
      public sources for nonrespondents. Covariates included gender, specialty, time
      distribution, and years in academia. Negative binomial regression was used for
      count data, logistic regression for binary outcomes, and linear regression for
      continuous outcomes. RESULTS: In productivity analyses, advancement, and
      retention, 1,270 participants were included; 604 participants responded to the
      compensation and satisfaction survey. Response rates were lower for African
      American (26%) and Hispanic faculty (39%) than white faculty (52%, P < .0001).
      URM faculty had lower rates of peer-reviewed publications (relative number 0.64;
      95% CI: 0.51, 0.79), promotion to professor (OR = 0.53; CI: 0.30, 0.93), and
      retention in academic medicine (OR = 0.49; CI: 0.32, 0.75). No differences were
      identified in federal grant acquisition, senior leadership roles, career
      satisfaction, or compensation between URM and white faculty. CONCLUSIONS: URM and
      white faculty had similar career satisfaction, grant support, leadership, and
      compensation; URM faculty had fewer publications and were less likely to be
      promoted and retained in academic careers. Successful retention of URM faculty
      requires comprehensive institutional commitment to changing the academic climate
      and deliberative programming to support productivity and advancement.

PMID- 29068823
TI  - Five Dimensions of Research Ethics: A Stakeholder Framework for Creating a
      Climate of Research Integrity.
AB  - The authors explore five dimensions of research ethics: (1) normative ethics,
      which includes meta-ethical questions; (2) compliance with regulations, statutes,
      and institutional policies; (3) the rigor and reproducibility of science; (4)
      social value; and (5) workplace relationships. Each of the five dimensions is
      important not only because it addresses an aspect of good research done in a good
      manner but also because it addresses the concerns of key stakeholders in the
      research enterprise. The five-dimension framework can guide institutions as they
      answer three questions central to any research ethics program: (1) Who should
      champion research ethics? (2) What should interventions look like? and (3) Who
      should participate in the interventions? The framework is valuable because the
      answers to these three questions are radically different depending on the
      dimension under consideration. An expanded vision of research ethics does not
      entail that institutions should require additional online training or approvals
      from institutional review boards. However, without acknowledging all five
      dimensions, programs risk missing an important aspect of research ethics or
      ignoring the interests of important stakeholders.

PMID- 29068824
TI  - Health Care Organizations and Policy Leadership: Perspectives on Nonsmoker-Only
      Hiring Policies.
AB  - PURPOSE: To explore employers' decisions to base hiring policies on tobacco or
      nicotine use and community perspectives on such policies, and analyze the
      implications for organizational identity, community engagement, and health
      promotion. METHOD: From 2013 to 2016, 11 executives from six health care
      organizations and one non-health-care organization with nonsmoker-only hiring
      policies were interviewed about why and how their policies were created and
      implemented, concerns about the policies, and perceptions of employee and public
      reactions. Focus groups were conducted with community members (n = 51) who lived
      in or near cities where participating employers were based, exploring
      participants' opinions about why an employer would stop hiring smokers and their
      support (or not) for such a policy. RESULTS: Most employers excluded from
      employment those using all forms of nicotine. Several explained their adoption of
      the policy as a natural extension of a smoke-free campus and as consistent with
      their identity as health care organizations. They regarded the policy as
      promoting health. No employer mentioned engaging in a community dialogue before
      adopting the policy or reported efforts to track the policy's impact on rejected
      applicants. Community members understood the cost-saving appeal of such policies,
      but most opposed them. They made few exceptions for health care organizations.
      CONCLUSIONS: Policy decisions undertaken by health care organizations have
      influence beyond their immediate setting and may establish precedents that others
      follow. Nonsmoker-only hiring policies may fit with a health care organization's
      institutional identity but may not be congruent with community values or promote
      public health.

PMID- 29068825
TI  - The Economic Burden of Pathological Gambling and Co-occurring Mental Health and
      Substance Use Disorders.
AB  - OBJECTIVES: Disordered gambling often co-occurs with psychiatric and substance
      use disorders. The study aim was to assess the healthcare costs of pathological
      gambling (PG) and co-occurring mental health and substance use disorders by
      payer. This is the first-of-its-kind economic analysis of addictive behaviors and
      mental health disorders. METHODS: Study data were derived from the Massachusetts
      All-Payer Claims Data-a representative health claims database-for the period 2009
      to 2013. The study analytical sample contained all medical and pharmaceutical
      claims for commercially insured Massachusetts residents who were aged >=18 years,
      had health insurance coverage, had a diagnosis of PG, and sought care in the
      Commonwealth. Healthcare cost components included outpatient, inpatient,
      emergency room visits, and prescription drugs. Bootstrap analysis was performed
      to account for skewed distribution of cost data. All costs were adjusted to
      constant dollars. RESULTS: The study sample included 599 patients over the study
      period. The most prevalent principal diagnoses were disorders of impulse control
      (50%), episodic mood disorders (31%), anxiety disorders (14%), and psychoactive
      substance (9%). The mean annual total expenditures on health care per patient
      with diagnosis of pathological gambling were $7993 +/- $11,847 (bias-corrected
      95% confidence interval) in 2009, $10,054 +/- $14,555 in 2010, $9093 +/- $13,422
      in 2011, and $9523 +/- $14,505 in 2012. Pharmaceutical expenditures represented
      16% to 22% of total healthcare expenditures. In the study period, prescription
      drug co-pays represented approximately 16% of the pharmaceutical expenditures.
      CONCLUSIONS: Psychiatric comorbidity and substance use disorders, and
      nondependent abuse of drugs are highly prevalent among pathological gamblers.
      These disorders pose an economic burden to patients and healthcare payers.

PMID- 29068826
TI  - Opioid Addiction in Pregnancy: Does Depression Negatively Impact Adherence With
      Prenatal Care?
AB  - OBJECTIVE: We aimed to evaluate whether depression in pregnancy in women with
      opioid dependency negatively impacts adherence with prenatal care. METHODS: This
      was a retrospective chart analysis of opioid-dependent pregnant women over a 6
      year period at 2 large referral and tertiary care centers. The primary outcome
      was adherence with prenatal care based on the concurrent diagnosis of depression.
      Adherence was assessed by looking at the number of observed versus expected
      prenatal visits. Secondary outcomes included neonatal intensive care unit (NICU)
      stay, and incidence and severity of neonatal abstinence syndrome (NAS). RESULTS:
      A total of 74 patient charts were reviewed. 45/74 (60.8%) of the opioid-dependent
      pregnant patients were either diagnosed with depression (n = 41), anxiety (n =
      2), or scored >10 on the Edinburgh Prenatal Depression Scale (n = 1). Patients
      with a diagnosis of depression were significantly less adherent with prenatal
      care; 80% adherent (73% vs 93%; P = 0.03), 90% adherent (62% vs 93%; P = 0.003).
      A higher number of patients in the depression group had an infant treated for
      withdrawal (62% vs 38%; P = 0.041), and had longer NICU stays (27% vs 21%; P =
      0.018). Analysis of the whole cohort of opioid dependent gravidas revealed
      Buprenorphine maintenance therapy had the lowest mean NAS score 6.5 +/- 4.4,
      compared with methadone maintenance 10.6 +/- 3.6, and no maintenance therapy 9.4
      +/- 4.0 (P = 0.008). CONCLUSION: Depression negatively impacts adherence with
      prenatal care and was significantly associated with a higher incidence of
      neonatal withdrawal and longer NICU stays. Buprenorphine therapy had the lowest
      incidence and severity of NAS when compared with methadone and no maintenance
      therapy.

PMID- 29068827
TI  - Predicting Smoking Lapses in the First Week of Quitting: An Ecological Momentary
      Assessment Study.
AB  - OBJECTIVES: This study focused on lapse shortly after an attempt to quit smoking.
      Ecological momentary assessment (EMA) studies have mapped real-time situational
      factors that induce lapses in everyday life. However, the possible role of
      nonsmoking intention is disregarded in the dynamic context of daily life, whereas
      intention plays a key role in behavior change and shifts during smoking
      cessation. This study therefore aimed to capture the influence of intention on
      lapse, next to the known risk factors of negative affect, low self-efficacy,
      craving, positive outcome expectations towards smoking (POEs), being around
      smokers, and stress. It is hypothesized that scores on these factors shift during
      the day, especially shortly after quitting, which may induce lapse. Based on
      behavioral explanation models, intention is hypothesized to mediate the influence
      of the mentioned factors on lapse. METHODS: An EMA study was conducted among 49
      self-quitters in the first week of smoking cessation. RESULTS: Generalized Linear
      Mixed Model regression analyses revealed that low nonsmoking intentions, low self
      efficacy, and being around smokers (estimates were, respectively, -0.303, -0.331,
      and 2.083) predicted lapse. Nonsmoking intention partially mediated the influence
      of self-efficacy on lapse. Nonsmoking intention was predicted by not being around
      smokers, high self-efficacy, and low POEs (estimates were, respectively, -0.353,
      0.293, and -0.072). CONCLUSIONS: This small-scale EMA study confirms the
      importance of nonsmoking intention on lapse, next to self-efficacy and being
      around smokers. It adds insights into the mediating role of intention on the
      relationship between self-efficacy and lapse, and into the predictors of
      nonsmoking intention.

PMID- 29068828
TI  - How to Catch Unicorns (and Other Fairytales).

PMID- 29068829
TI  - Vigilance Research and Just Culture Principles: Challenges for a Connected
      Perioperative World.

PMID- 29068831
TI  - Crystalloid versus Colloid for Intraoperative Goal-directed Fluid Therapy Using a
      Closed-loop System: A Randomized, Double-blinded, Controlled Trial in Major
      Abdominal Surgery.
AB  - BACKGROUND: The type of fluid and volume regimen given intraoperatively both can
      impact patient outcome after major surgery. This two-arm, parallel, randomized
      controlled, double-blind, bi-center superiority study tested the hypothesis that
      when using closed-loop assisted goal-directed fluid therapy, balanced colloids
      are associated with fewer postoperative complications compared to balanced
      crystalloids in patients having major elective abdominal surgery. METHODS: One
      hundred and sixty patients were enrolled in the protocol. All patients had
      maintenance-balanced crystalloid administration of 3 ml . kg . h. A closed-loop
      system delivered additional 100-ml fluid boluses (patients were randomized to
      receive either a balanced-crystalloid or colloid solution) according to a
      predefined goal-directed strategy, using a stroke volume and stroke volume
      variation monitor. All patients were included in the analysis. The primary
      outcome was the Post-Operative Morbidity Survey score, a nine-domain scale, at
      day 2 postsurgery. Secondary outcomes included all postoperative complications.
      RESULTS: Patients randomized in the colloid group had a lower Post-Operative
      Morbidity Survey score (median [interquartile range] of 2 [1 to 3] vs. 3 [1 to
      4], difference -1 [95% CI, -1 to 0]; P < 0.001) and a lower incidence of
      postoperative complications. Total volume of fluid administered intraoperatively
      and net fluid balance were significantly lower in the colloid group. CONCLUSIONS:
      Under our study conditions, a colloid-based goal-directed fluid therapy was
      associated with fewer postoperative complications than a crystalloid one. This
      beneficial effect may be related to a lower intraoperative fluid balance when a
      balanced colloid was used. However, given the study design, the mechanism for the
      difference cannot be determined with certainty.

PMID- 29068832
TI  - Infected Nasal Dermoid Cyst/Sinus Tract Presenting With Bilateral Subperiosteal
      Supraorbital Abscesses: The Midline Nasal Tuft of Hair, an Overlooked Finding.
AB  - This case is, to the authors' knowledge, the first reported case in the
      literature of bilateral orbital abscesses as result of an infected nasal dermoid.
      The baby presented with what proved to be bilateral supraorbital subperiosteal
      abscesses with associated frontal osteitis/osteomyelitis and soft tissue
      infection of the glabella. Methicillin-sensitive staphylococcus aureus infection
      was found in the setting of a midline nasal dermoid with tuft of hair and
      infected sinus tract that was at least initially missed on diagnosis.

PMID- 29068830
TI  - Propofol-induced Changes in alpha-beta Sensorimotor Cortical Connectivity.
AB  - BACKGROUND: Anesthetics are believed to alter functional connectivity across
      brain regions. However, network-level analyses of anesthesia, particularly in
      humans, are sparse. The authors hypothesized that propofol-induced loss of
      consciousness results in functional disconnection of human sensorimotor cortices
      underlying the loss of volitional motor responses. METHODS: The authors recorded
      local field potentials from sensorimotor cortices in patients with Parkinson
      disease (N = 12) and essential tremor (N = 7) undergoing deep brain stimulation
      surgery, before and after propofol-induced loss of consciousness. Local spectral
      power and interregional connectivity (coherence and imaginary coherence) were
      evaluated separately across conditions for the two populations. RESULTS: Propofol
      anesthesia caused power increases for frequencies between 2 and 100 Hz across the
      sensorimotor cortices and a shift of the dominant spectral peak in alpha and beta
      frequencies toward lower frequencies (median +/- SD peak frequency: 24.5 +/- 2.6
      Hz to 12.8 +/- 2.3 Hz in Parkinson disease; 13.8 +/- 2.1 Hz to 12.1 +/- 1.0 Hz in
      essential tremor). Despite local increases in power, sensorimotor cortical
      coherence was suppressed with propofol in both cohorts, specifically in beta
      frequencies (18 to 29 Hz) for Parkinson disease and alpha and beta (10 to 48 Hz)
      in essential tremor. CONCLUSIONS: The decrease in functional connectivity between
      sensory and motor cortices, despite an increase in local spectral power, suggests
      that propofol causes a functional disconnection of cortices with increases in
      autonomous activity within cortical regions. This pattern occurs across diseases
      evaluated, suggesting that these may be generalizable effects of propofol in
      patients with movement disorders and beyond. Sensorimotor network disruption may
      underlie anesthetic-induced loss of volitional control.

PMID- 29068833
TI  - Adult T-Cell Leukemia/Lymphoma With Primary Lacrimal Gland Involvement.
AB  - A 69-year-old Japanese male presented with a 3-month history of bilateral ptosis
      with lacrimal gland bulge. He came from western Japan, an area endemic for human
      T-lymphotropic virus Type 1 infection. Physical examination and imaging revealed
      bilaterally enlarged lacrimal glands. Hematologic testing, biopsy with
      histopathology, and immunohistochemistry were all consistent with adult T-cell
      leukemia/lymphoma.

PMID- 29068834
TI  - Serum suppression of tumorigenicity 2 level is an independent predictor of all
      cause mortality in HIV-infected patients.
AB  - OBJECTIVE: To evaluate the predictive value of soluble suppression of
      tumorigenicity 2 (sST2), a decoy receptor of IL-33 involved in several
      inflammatory and immune diseases, for death in HIV infection. DESIGN: Patients
      enrolled in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of
      HIV-1-infected patients, who had a plasma sample available in the biobank were
      systematically eligible. METHODS: sST2, soluble CD14 (sCD14) and IL-6 were
      measured using Luminex multiplex bead-based technology (R&D Systems) and a Bio
      Plex 200 instrument (BioRad). Predictive capacities of sST2, sCD14, IL-6 and of
      the Veterans Aging Cohort Study clinical score at baseline on overall mortality
      were compared using multivariable Cox proportional hazards models. RESULTS:
      During a median follow-up of 7.2 years [interquartile range (IQR): 6.0; 7.9], 93
      deaths from all causes (incidence rate 9.9 per 1000 patient-years; 95% confidence
      interval 7.9-11.9) were reported in 1414 patients. The median sST2 baseline
      concentration was 22.9 ng/ml (IQR: 17.7; 30.3) and was higher (30.8 ng/ml, IQR:
      21.5; 42.1) in patients who died as compared with those who stayed alive (22.6
      ng/ml; IQR: 17.5; 29.6) (P < 10). An increased risk of death of 21% for a
      concentration 10.0 ng/ml higher of sST2 remained after adjustment for sCD14, IL-6
      and Veterans Aging Cohort Study score (adjusted hazard ratio: 1.21; P < 10). The
      predictive capacity of sST2 was confirmed in a validation cohort (n = 386, 31
      deaths) with an improved area c-index from 0.804 without sST2 to 0.811 with sST2.
      CONCLUSION: sST2 is a new valuable biomarker to evaluate the risk of all-cause
      mortality in HIV disease.

PMID- 29068835
TI  - Need to include couples' HIV counselling and testing as a strategy to improve HIV
      partner notification services.

PMID- 29068836
TI  - Reaching people with undiagnosed HIV infection through assisted partner
      notification.

PMID- 29068837
TI  - HIV criminalization exacerbates subpar diagnosis and treatment across the United
      States: response to the 'Association of HIV diagnosis rates and laws
      criminalizing HIV exposure in the United States'.

PMID- 29068838
TI  - Extending the Case-Control Design to Longitudinal Data: Stratified Sampling Based
      on Repeated Binary Outcomes.
AB  - We detail study design options that generalize case-control sampling when
      longitudinal outcome data are already collected as part of a primary cohort
      study, but new exposure data must be retrospectively processed for a secondary
      analysis. Furthermore, we assume that cost will limit the size of the subsample
      that can be evaluated. We describe a novel class of stratified outcome-dependent
      sampling designs for longitudinal binary response data where distinct strata are
      created for subjects who never, sometimes, and always experienced the event of
      interest during longitudinal follow-up. Individual designs within this class are
      differentiated by the stratum-specific sampling probabilities. We show for
      parameters associated with time-varying exposures, subjects who experience the
      event/outcome at some but not at all of the follow-up times (i.e., those who
      exhibit response variation) are highly informative. If the time-varying exposure
      varies exclusively within individuals (i.e., intraclass correlation coefficient
      is 0), then sampling all subjects with response variability can yield highly
      precise parameter estimates even when compared with an analysis of the original
      cohort. The flexibility of the designs and analysis procedures also permits
      estimation of parameters that correspond to time-fixed covariates, and we show
      that with an imputation-based estimation procedure, baseline covariate
      associations can be estimated with very high precision irrespective of the
      design. We demonstrate features of the designs and analysis procedures via a
      plasmode simulation using data from the Lung Health Study.

PMID- 29068839
TI  - New Designs for New Epidemiology.

PMID- 29068840
TI  - On the Analysis of Case-Control Studies in Cluster-correlated Data Settings.
AB  - In resource-limited settings, long-term evaluation of national antiretroviral
      treatment (ART) programs often relies on aggregated data, the analysis of which
      may be subject to ecological bias. As researchers and policy makers consider
      evaluating individual-level outcomes such as treatment adherence or mortality,
      the well-known case-control design is appealing in that it provides efficiency
      gains over random sampling. In the context that motivates this article, valid
      estimation and inference requires acknowledging any clustering, although, to our
      knowledge, no statistical methods have been published for the analysis of case
      control data for which the underlying population exhibits clustering.
      Furthermore, in the specific context of an ongoing collaboration in Malawi,
      rather than performing case-control sampling across all clinics, case-control
      sampling within clinics has been suggested as a more practical strategy. To our
      knowledge, although similar outcome-dependent sampling schemes have been
      described in the literature, a case-control design specific to correlated data
      settings is new. In this article, we describe this design, discuss balanced
      versus unbalanced sampling techniques, and provide a general approach to
      analyzing case-control studies in cluster-correlated settings based on inverse
      probability-weighted generalized estimating equations. Inference is based on a
      robust sandwich estimator with correlation parameters estimated to ensure
      appropriate accounting of the outcome-dependent sampling scheme. We conduct
      comprehensive simulations, based in part on real data on a sample of N = 78,155
      program registrants in Malawi between 2005 and 2007, to evaluate small-sample
      operating characteristics and potential trade-offs associated with standard case
      control sampling or when case-control sampling is performed within clusters.

PMID- 29068842
TI  - From the Editors.

PMID- 29068843
TI  - Addressing the Global Zika Epidemic and Interprofessional Model of Universal
      Screening.

PMID- 29068844
TI  - Response to Letter to the Editor.

PMID- 29068841
TI  - Outcome-related, Auxiliary Variable Sampling Designs for Longitudinal Binary
      Data.
AB  - BACKGROUND: Epidemiologists have long used case-control and related study designs
      to enhance variability of response and information available to estimate exposure
      disease associations. Less has been done for longitudinal data. METHODS: We
      discuss an epidemiological study design and analysis approach for longitudinal
      binary response data. We seek to gain statistical efficiency by oversampling
      relatively informative subjects for inclusion into the sample. In this
      methodological demonstration, we develop this concept by sampling repeatedly from
      an existing cohort study to estimate the relationship of chronic obstructive
      pulmonary disease to past-year smoking in a panel of baseline smokers. To account
      for oversampling, we describe a sequential offsetted regressions approach for
      valid inferences in this setting. RESULTS: Targeted sampling can lead to
      increased statistical efficiency when combined with sequential offsetted
      regressions. Efficiency gains are degraded with increased prevalence of the
      disease response variable, with decreased association between the sampling
      variable and the response, and with other design and analysis parameters,
      providing guidance to those wishing to use these types of designs in the future.
      CONCLUSIONS: These designs hold promise for efficient use of resources in
      longitudinal cohort studies.

PMID- 29068845
TI  - Update: Simulation-Based Training.

PMID- 29068846
TI  - Optimizing the Birth Environment With Evidence-Based Design.

PMID- 29068847
TI  - Cognitive Bias: A Potential Threat to Clinical Decision-Making in the Neonatal
      Intensive Care Unit.

PMID- 29068848
TI  - The Latest Headache for Clinicians: Head Compression and Brain Injury.

PMID- 29068849
TI  - Acid Suppressant Medications in the Neonatal Intensive Care Unit: Strategies for
      Appropriate Use.

PMID- 29068850
TI  - Systematic Review of Hydrotherapy Research: Does a Warm Bath in Labor Promote
      Normal Physiologic Childbirth?

PMID- 29068852
TI  - Effectiveness of Intracavitary Electrocardiogram Guidance in Peripherally
      Inserted Central Catheter Tip Placement in Neonates.

PMID- 29068851
TI  - Perinatal Nurses Reported to Boards of Nursing: Understanding the Facts.
AB  - Today's healthcare system is in a state of transformation, as changes in
      technology, diagnostic approaches, treatments, and levels of professional
      practice occur on a regular basis. Nurses continue to be the most trusted
      profession. What has not changed in clinical practice is the amount of
      responsibility and level of accountability. Therefore, nurses are morally,
      legally, and ethically responsible for nursing judgment and clinical-based
      actions covered under each state's Nurse Practice Act, the American Nurses
      Association's core principles, and position statements as well as standard
      setting documents from professional organizations. Unfortunately, mistakes happen
      in an enormous system where human error cannot be entirely avoided, which is why
      being named in a board of nursing complaint can be so devastating. Stress and
      accusations of not providing reasonable or prudent care can be overwhelming,
      which may impact a perinatal clinician's health. This article's purpose is to
      provide information about the process of a board of nursing complaint, potential
      sequelae of an investigation, as well as best practices to decrease risk,
      focusing exclusively on perinatal nurses and advanced practice providers.

PMID- 29068853
TI  - Neonatal Rhizomelic Chondrodysplasia Punctata Type 1: Weaving Evidence Into
      Clinical Practice.
AB  - Rhizomelic chondrodysplasia punctata (RCDP) is a rare genetic peroxisome
      biogenesis disorder with a reported incidence of 1 in 100 000 live births. The 3
      genetic subtypes of RCDP are acquired by an autosomal recessive inheritance
      pattern. RCDP type 1 accounts for greater than 90% of all aggregate cases.
      Differentiating between the 3 subtypes of RCDP, as well as disorders
      characterized by similar punctate cartilaginous changes, is essential to guide an
      appropriate postnatal plan of care. Management strategies are focused toward
      associated clinical manifestations and require an interdisciplinary approach
      including ophthalmology, cardiovascular, endocrine, physical and occupational
      therapy, and neurology. Purposeful and frequent collaboration among all members
      of the neonatal/pediatric interdisciplinary team is necessary to optimize
      outcomes for the neonate and the family unit. The purpose of this article is to
      anticipate the needs of both patients with known and prenatal diagnosis of RCDP
      type 1 and patients with suspected clinical diagnosis of RCDP type 1 in the
      immediate neonatal period and to guide the appropriate plan of care. This article
      presents a case report of type I RCDP, as well as describes genetic influences,
      symptoms, diagnosis, management, and prognosis.

PMID- 29068854
TI  - Complaints of an Aging Nurse.

PMID- 29068856
TI  - Should We Manage All Septic Patients Based on a Single Definition? An Alternative
      Approach.

PMID- 29068855
TI  - Development and Validation of an Abbreviated Questionnaire to Easily Measure
      Cognitive Failure in ICU Survivors: A Multicenter Study.
AB  - OBJECTIVES: To develop and validate an abbreviated version of the Cognitive
      Failure Questionnaire that can be used by patients as part of self-assessment to
      measure functional cognitive outcome in ICU survivors. DESIGN: A retrospective
      multicenter observational study. SETTING: The ICUs of two Dutch university
      hospitals. PATIENTS: Adult ICU survivors. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Cognitive functioning was evaluated between 12 and 24 months after
      ICU discharge using the full 25-item Cognitive Failure Questionnaire (CFQ-25).
      Incomplete CFQ-25 questionnaires were excluded from analysis. Forward selection
      in a linear regression model was used in hospital A to assess which of the CFQ-25
      items should be included to prevent a significant loss of correlation between an
      abbreviated and the full CFQ-25. Subsequently, the performance of an abbreviated
      Cognitive Failure Questionnaire was determined in hospital B using Pearson's
      correlation. A Bland-Altman plot was used to examine whether the reduced-item
      outcome scores of an abbreviated Cognitive Failure Questionnaire were a
      replacement for the full CFQ-25 outcome scores. Among 1,934 ICU survivors, 1,737
      were included, 819 in hospital A, 918 in hospital B. The Pearson's correlation
      between the abbreviated 14-item Cognitive Failure Questionnaire (CFQ-14) and the
      CFQ-25 was 0.99. The mean of the difference scores was -0.26, and 95% of the
      difference scores fell within +5 and -5.5 on a 100-point maximum score.
      CONCLUSIONS: It is feasible to use the abbreviated CFQ-14 to measure self
      reported cognitive failure in ICU survivors as this questionnaire has a similar
      performance as the full CFQ-25.

PMID- 29068857
TI  - 24-Hour Intensivist Staffing Is Not Beneficial for Patients.

PMID- 29068858
TI  - Outcomes of Ventilated Patients With Sepsis Who Undergo Interhospital Transfer: A
      Nationwide Linked Analysis.
AB  - OBJECTIVES: The outcomes of critically ill patients who undergo interhospital
      transfer are not well understood. Physicians assume that patients who undergo
      interhospital transfer will receive more advanced care that may translate into
      decreased morbidity or mortality relative to a similar patient who is not
      transferred. However, there is little empirical evidence to support this
      assumption. We examined country-level U.S. data from the Nationwide Readmissions
      Database to examine whether, in mechanically ventilated patients with sepsis,
      interhospital transfer is associated with a mortality benefit. DESIGN:
      Retrospective data analysis using complex survey design regression methods with
      propensity score matching. SETTING: The Nationwide Readmissions Database contains
      information about hospital admissions from 22 States, accounting for roughly half
      of U.S. hospitalizations; the database contains linkage numbers so that
      admissions and transfers for the same patient can be linked across 1 year of
      follow-up. PATIENTS: From the 2013 Nationwide Readmission Database Sample,
      14,325,172 hospital admissions were analyzed. There were 61,493 patients with
      sepsis and on mechanical ventilation. Of these, 1,630 patients (2.7%) were
      transferred during their hospitalization. A propensity-matched cohort of 1,630
      patients who did not undergo interhospital transfer was identified.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was
      interhospital transfer to an acute care facility. The primary outcome was
      hospital mortality; the secondary outcome was hospital length of stay. The
      propensity score included age, gender, insurance coverage, do not resuscitate
      status, use of renal replacement therapy, presence of shock, and Elixhauser
      comorbidities index. After propensity matching, interhospital transfer was not
      associated with a difference in in-hospital mortality (12.3% interhospital
      transfer vs 12.7% non-interhospital transfer; p = 0.74). However, interhospital
      transfer was associated with a longer total hospital length of stay (12.8 d
      interquartile range, 7.7-21.6 for interhospital transfer vs 9.1 d interquartile
      range, 5.1-17.0 for non-interhospital transfer; p < 0.01). CONCLUSIONS: Patients
      with sepsis requiring mechanical ventilation who underwent interhospital transfer
      did not have improved outcomes compared with a cohort with matched
      characteristics who were not transferred. The study raises questions about the
      risk-benefit profile of interhospital transfer as an intervention.

PMID- 29068860
TI  - Validating a Method to Assess Lipreading, Audiovisual Gain, and Integration
      During Speech Reception With Cochlear-Implanted and Normal-Hearing Subjects Using
      a Talking Head.
AB  - OBJECTIVES: Watching a talker's mouth is beneficial for speech reception (SR) in
      many communication settings, especially in noise and when hearing is impaired.
      Measures for audiovisual (AV) SR can be valuable in the framework of diagnosing
      or treating hearing disorders. This study addresses the lack of standardized
      methods in many languages for assessing lipreading, AV gain, and integration. A
      new method is validated that supplements a German speech audiometric test with
      visualizations of the synthetic articulation of an avatar that was used, for it
      is feasible to lip-sync auditory speech in a highly standardized way. Three
      hypotheses were formed according to the literature on AV SR that used live or
      filmed talkers. It was tested whether respective effects could be reproduced with
      synthetic articulation: (1) cochlear implant (CI) users have a higher visual-only
      SR than normal-hearing (NH) individuals, and younger individuals obtain higher
      lipreading scores than older persons. (2) Both CI and NH gain from presenting AV
      over unimodal (auditory or visual) sentences in noise. (3) Both CI and NH
      listeners efficiently integrate complementary auditory and visual speech
      features. DESIGN: In a controlled, cross-sectional study with 14 experienced CI
      users (mean age 47.4) and 14 NH individuals (mean age 46.3, similar broad age
      distribution), lipreading, AV gain, and integration of a German matrix sentence
      test were assessed. Visual speech stimuli were synthesized by the articulation of
      the Talking Head system "MASSY" (Modular Audiovisual Speech Synthesizer), which
      displayed standardized articulation with respect to the visibility of German
      phones. RESULTS: In line with the hypotheses and previous literature, CI users
      had a higher mean visual-only SR than NH individuals (CI, 38%; NH, 12%; p <
      0.001). Age was correlated with lipreading such that within each group, younger
      individuals obtained higher visual-only scores than older persons (rCI = -0.54; p
      = 0.046; rNH = -0.78; p < 0.001). Both CI and NH benefitted by AV over unimodal
      speech as indexed by calculations of the measures visual enhancement and auditory
      enhancement (each p < 0.001). Both groups efficiently integrated complementary
      auditory and visual speech features as indexed by calculations of the measure
      integration enhancement (each p < 0.005). CONCLUSIONS: Given the good agreement
      between results from literature and the outcome of supplementing an existing
      validated auditory test with synthetic visual cues, the introduced method can be
      considered an interesting candidate for clinical and scientific applications to
      assess measures important for AV SR in a standardized manner. This could be
      beneficial for optimizing the diagnosis and treatment of individual listening and
      communication disorders, such as cochlear implantation.

PMID- 29068859
TI  - Racial and Geographic Disparities in Interhospital ICU Transfers.
AB  - OBJECTIVES: Interhospital transfer, a common intervention, may be subject to
      healthcare disparities. In mechanically ventilated patients with sepsis, we
      hypothesize that disparities not disease related would be found between patients
      who were and were not transferred. DESIGN: Retrospective cohort study. SETTING:
      Nationwide Inpatient Sample, 2006-2012. PATIENTS: Patients over 18 years old with
      a primary diagnosis of sepsis who underwent mechanical ventilation.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We obtained age, gender,
      length of stay, race, insurance coverage, do not resuscitate status, and
      Elixhauser comorbidities. The outcome used was interhospital transfer from a
      small- or medium-sized hospital to a larger acute care hospital. Of 55,208,382
      hospitalizations, 46,406 patients met inclusion criteria. In the multivariate
      model, patients were less likely to be transferred if the following were present:
      older age (odds ratio, 0.98; 95% CI, 0.978-0.982), black race (odds ratio, 0.79;
      95% CI, 0.70-0.89), Hispanic race (odds ratio, 0.79; 95% CI, 0.69-0.90), South
      region hospital (odds ratio, 0.79; 95% CI, 0.72-0.88), teaching hospital (odds
      ratio, 0.31; 95% CI, 0.28-0.33), and do not resuscitate status (odds ratio, 0.19;
      95% CI, 0.15-0.25). CONCLUSIONS: In mechanically ventilated patients with sepsis,
      we found significant disparities in race and geographic location not explained by
      medical diagnoses or illness severity.

PMID- 29068861
TI  - Prevalence of and Risk Factors for Tinnitus and Tinnitus-Related Handicap in a
      College-Aged Population.
AB  - OBJECTIVE: Tinnitus is a common otological condition that affects almost 10% of
      US adults. Research suggests that college students are vulnerable to tinnitus and
      hearing loss as they are exposed to traumatic levels of noise on a regular basis.
      Tinnitus and its influence in daily living continue to be underappreciated in the
      college-aged population. Therefore, the objective for the present study was to
      analyze prevalence and associated risk factors of tinnitus and tinnitus-related
      handicap in a sample of college-aged students. DESIGN: A survey was administered
      to 678 students aged 18-30 years in a cross-section of randomly selected
      university classes. The survey was adopted from the National Health and Nutrition
      Examination Survey (2010). It inquired about demographic details, medical and
      audiological history, routine noise exposure, smoking, sound level tolerance,
      tinnitus, and tinnitus-related handicap in daily living. Tinnitus-related
      handicap was assessed by the Tinnitus Handicap Inventory (THI). Participants were
      divided into four groups: chronic tinnitus (bothersome tinnitus for >1 year),
      acute tinnitus (bothersome tinnitus for <=1 year), subacute tinnitus (at least
      one experience of tinnitus in a lifetime), and no tinnitus (no experience of
      tinnitus in a lifetime). RESULTS: The prevalence of chronic, acute, subacute, and
      no tinnitus was 8.4%, 13.0%, 37.9%, and 40.7% respectively. Almost 9% of subjects
      with any form of tinnitus reported more than a slight tinnitus-related handicap
      (i.e., THI score >=18). A multinomial regression analysis revealed that
      individuals with high noise exposure, high sound level tolerance score, recurring
      ear infections, and self-reported hearing loss had high odds of chronic tinnitus.
      Females showed higher prevalence of acute tinnitus than males. Individuals with
      European American ethnicity and smoking history showed high odds of reporting
      subacute tinnitus. Almost 10% of the subjects reported that they were music
      students. The prevalence of chronic, acute, and subacute tinnitus was 11.3%,
      22.5%, and 32.4%, respectively, for musicians, which was significantly higher
      than that for nonmusicians. Music exposure, firearm noise exposure, and
      occupational noise exposure were significantly correlated with tinnitus. Temporal
      characteristics of tinnitus, self-reported tinnitus loudness, and sound level
      tolerance were identified as major predictors for the overall THI score.
      CONCLUSIONS: Despite the reluctance to complain about tinnitus, a substantial
      portion of college-aged individuals reported tinnitus experience and its adverse
      influence in daily living. It was concluded that environmental and health-related
      factors can trigger tinnitus perception, while self-reported psychoacoustic
      descriptors of tinnitus may explain perceived tinnitus-related handicap in daily
      living by college-aged individuals. Future research is required to explore
      effects of tinnitus on educational achievements, social interaction, and
      vocational aspects of college students.

PMID- 29068863
TI  - Activity of Lower Limb Muscles During Squat With and Without Abdominal Drawing-in
      and Pilates Breathing.
AB  - Barbosa, AC, Martins, FM, Silva, AF, Coelho, AC, Intelangelo, L, and Vieira, ER.
      Activity of lower limb muscles during squat with and without abdominal drawing-in
      and Pilates breathing. J Strength Cond Res 31(11): 3018-3023, 2017-The purpose of
      this study was to assess the effects of abdominal drawing-in and Pilates
      breathing on the activity of lower limb muscles during squats. Adults (n = 13, 22
      +/- 3 years old) with some Pilates experience performed three 60 degrees  squats
      under each of the following conditions in a random order: (I) normal breathing,
      (II) drawing-in maneuver with normal breathing, and (III) drawing-in maneuver
      with Pilates breathing. Peak-normalized surface electromyography of the rectus
      femoris, biceps femoris, gastrocnemius medialis, and tibialis anterior during the
      knee flexion and extension phases of squat exercises was analyzed. There were
      significant differences among the conditions during the knee flexion phase for
      the rectus femoris (p = 0.001), biceps femoris (p = 0.038), and tibialis anterior
      (p = 0.001), with increasing activation from conditions I to III. For the
      gastrocnemius medialis, there were significant differences among the conditions
      during the knee extension phase (p = 0.023), with increased activity under
      condition I. The rectus and biceps femoris activity was higher during the
      extension vs. flexion phase under conditions I and II. The tibialis anterior
      activity was higher during the flexion compared with the extension phase under
      all conditions, and the medial gastrocnemius activity was higher during the
      extension phase under condition I. Doing squats with abdominal drawing-in and
      Pilates breathing resulted in increased rectus, biceps femoris, and tibialis
      anterior activity during the flexion phase, increasing movement stability during
      squat exercises.

PMID- 29068862
TI  - Impact of Polyphenol Supplementation on Acute and Chronic Response to Resistance
      Training.
AB  - Beyer, KS, Stout, JR, Fukuda, DH, Jajtner, AR, Townsend, JR, Church, DD, Wang, R,
      Riffe, JJ, Muddle, TWD, Herrlinger, KA, and Hoffman, JR. Impact of polyphenol
      supplementation on acute and chronic response to resistance training. J Strength
      Cond Res 31(11): 2945-2954, 2017-This study investigated the effect of a
      proprietary polyphenol blend (PPB) on acute and chronic adaptations to resistance
      exercise. Forty untrained men were assigned to control, PPB, or placebo.
      Participants in PPB or placebo groups completed a 4-week supplementation period
      (phase I), an acute high-volume exercise bout (phase II), and a 6-week resistance
      training program (phase III); whereas control completed only testing during phase
      II. Blood draws were completed during phases I and II. Maximal strength in squat,
      leg press, and leg extension were assessed before and after phase III. The
      exercise protocol during phase II consisted of squat, leg press, and leg
      extension exercises using 70% of the participant's strength. The resistance
      training program consisted of full-body exercises performed 3 d.wk. After phase
      I, PPB (1.56 +/- 0.48 mM) had greater total antioxidant capacity than placebo
      (1.00 +/- 0.90 mM). Changes in strength from phase III were similar between PPB
      and placebo. Polyphenol blend supplementation may be an effective strategy to
      increase antioxidant capacity without limiting strength gains from training.

PMID- 29068864
TI  - Monitoring Training Load in Handcycling: A Case Study.
AB  - Zeller, S, Abel, T, and Strueder, HK. Monitoring training load in handcycling: a
      case study. J Strength Cond Res 31(11): 3094-3100, 2017-The aim of this study was
      to analyze the training intensity distribution (TID) and the total training load
      (TTL) for the first time in handcycling of a multiple female Paralympic medalist
      (lesion level: L2-3 incomplete, ASIA C, classification: WH5). This study focuses
      on the preparation and the competitive period of the 2015 season. The athlete
      completed 194 handcycling training sessions in a time of 433:53 hours, covering a
      total distance of 10.190 km. An average training week consisted of 9:38 +/- 4:50
      hours of training during 4.3 +/- 1.5 training sessions. Training was categorized
      according to the 3-zone intensity scale (zone 1: below blood lactate levels of 2
      mmol.L; zone 2: between 2 mmol.L and 4 mmol.L; and zone 3: above 4 mmol.L). The
      average TID during the observation was 71.6 +/- 14.9% in zone 1, 15.2 +/- 8.0% in
      zone 2, and 13.1 +/- 5.5% in zone 3. The analysis of TID throughout the season
      demonstrates a tendency toward a greater volume in zone 2 than the
      recommendations in the literature. The mean TTL throughout the season was 804 +/-
      399 arbitrary units. During the investigation, the performance capacity in the
      incremental exercise test analog to 4 mmol.L increased by 19% (150-181 W),
      whereas the peak power output improved by 22% (180-200 W). Currently, no general
      guideline for the TTL and TID in paraplegic endurance athletes can be given.

PMID- 29068865
TI  - Effect of a Lower Extremity Preventive Training Program on Physical Performance
      Scores in Military Recruits.
AB  - Peck, KY, DiStefano, LJ, Marshall, SW, Padua, DA, Beutler, AI, de la Motte, SJ,
      Frank, BS, Martinez, JC, and Cameron, KL. Effect of a lower extremity preventive
      training program on physical performance scores in military recruits. J Strength
      Cond Res 31(11): 3146-3157, 2017-Exercise-based preventive training programs are
      designed to improve movement patterns associated with lower extremity injury
      risk; however, the impact of these programs on general physical fitness has not
      been evaluated. The purpose of this study was to compare fitness scores between
      participants in a preventive training program and a control group. One thousand
      sixty-eight freshmen from a U.S. Service Academy were cluster-randomized into
      either the intervention or control group during 6 weeks of summer training. The
      intervention group performed a preventive training program, specifically the
      Dynamic Integrated Movement Enhancement (DIME), which is designed to improve
      lower extremity movement patterns. The control group performed the Army
      Preparation Drill (PD), a warm-up designed to prepare soldiers for training. Main
      outcome measures were the Army Physical Fitness Test (APFT) raw and scaled (for
      age and sex) scores. Independent t tests were used to assess between-group
      differences. Multivariable logistic regression models were used to control for
      the influence of confounding variables. Dynamic Integrated Movement Enhancement
      group participants completed the APFT 2-mile run 20 seconds faster compared with
      the PD group (p < 0.001), which corresponded with significantly higher scaled
      scores (p < 0.001). Army Physical Fitness Test push-up scores were significantly
      higher in the DIME group (p = 0.041), but there were no significant differences
      in APFT sit-up scores. The DIME group had significantly higher total APFT scores
      compared with the PD group (p < 0.001). Similar results were observed in
      multivariable models after controlling for sex and body mass index (BMI).
      Committing time to the implementation of a preventive training program does not
      appear to negatively affect fitness test scores.

PMID- 29068866
TI  - Does Flywheel Paradigm Training Improve Muscle Volume and Force? A Meta-Analysis.
AB  - Nunez Sanchez, FJ and Saez de Villarreal, E. Does flywheel paradigm training
      improve muscle volume and force? A meta-analysis. J Strength Cond Res 31(11):
      3177-3186, 2017-Several studies have confirmed the efficacy of flywheel paradigm
      training for improving or benefiting muscle volume and force. A meta-analysis of
      13 studies with a total of 18 effect sizes was performed to analyse the role of
      various factors on the effectiveness of flywheel paradigm training. The following
      inclusion criteria were employed for the analysis: (a) randomized studies; (b)
      high validity and reliability instruments; (c) published in a high quality peer
      reviewed journal; (d) healthy participants; (e) studies where the eccentric
      programme were described; and (f) studies where increases in muscle volume and
      force were measured before and after training. Increases in muscle volume and
      force were noted through the use of flywheel systems during short periods of
      training. The increase in muscle mass appears was not influenced by the existence
      of eccentric overload during the exercise. The increase in force was
      significantly higher with the existence of eccentric overload during the
      exercise. The responses identified in this analysis are essential and should be
      considered by strength and conditioning professionals regarding the most
      appropriate dose response trends for flywheel paradigm systems to optimize the
      increase in muscle volume and force.

PMID- 29068867
TI  - Low Expression of miR-18a as a Characteristic of Pediatric Acute Lymphoblastic
      Leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) occurs in both adults and children
      but the response to chemotherapy and survival is significantly worse in the
      adults. We aimed to study whether the expression of immune system-associated
      miRNAs would differ between adult and pediatric patients with ALL at the time of
      diagnosis. MATERIALS AND METHODS: Inflammation-associated miRNA analysis was
      performed in 19 adults and 79 pediatric patients with ALL and involved miR-10,
      miR-15, miR-16, miR-17-92 cluster, miR-33, miR-146a, miR-150, miR-155, miR-181a,
      miR-222, miR-223, and miR-339. MiRNAs were first analyzed by miRNA microarray and
      thereafter validated by qRT-PCR. Sufficient RNA for qRT-PCR was available for 42
      pediatric and 19 adult patients. RESULTS: Of the studied miRNAs, only miR-18a
      differed significantly in microarray analysis between adult and pediatric ALL,
      being lower in children (FC, -3.74; P, 0.0037). Results were confirmed by qRT-PCR
      (down-regulated in pediatric patients, P 0.003161). The other members of the miR
      17-92 cluster did not differ significantly. CONCLUSIONS: Pediatric and adult
      patients with ALL have remarkably similar patterns of immune-cell-associated
      miRNAs in their bone marrow at diagnosis. However, the low expression of miR-18a
      in pediatric ALL is interesting and demands further study.

PMID- 29068868
TI  - Elevated Serum Interleukin-6 Predicts Favorable Response to Immunosuppressive
      Therapy in Children With Aplastic Anemia.
AB  - BACKGROUND: Immunosuppressive therapy (IST) is the standard treatment for
      aplastic anemia (AA) children who lack a sibling donor, but the clinical response
      rate to IST varies. Predictors of response to IST are valuable for stratifying AA
      patients and making clinical decisions. METHODS: The serum interleukin (IL)-6
      levels of 41 AA patients were measured at the time of diagnosis and the response
      rate of the patients to IST was evaluated at 3, 6, and 12 months after IST.
      Receiver-operator characteristic (ROC) analysis was used to calculate the
      predictive value of initial IL-6 levels in determining response at 6 months after
      IST. RESULTS: The initial IL-6 levels were significant higher in responders than
      nonresponders at 6 months after IST (211.89 vs. 18.09 pg/mL; P=0.005), using 36.8
      pg/mL as a threshold, there were 80% sensitivity and 81% specificity for
      discriminating responders and nonresponders to IST. Patients with initial high IL
      6 level (>36.8 pg/mL) have favorable response rates than those with initial low
      IL-6 level (<36.8 pg/mL) at 3, 6, and 12 months after IST (P<0.01). CONCLUSION:
      High levels of IL-6 at the time of diagnosis predict a favorable response to IST
      in children with AA and this may be helpful for patient's stratification and
      clinical decisions.

PMID- 29068869
TI  - Dural Venous Sinus Thrombosis and Pulmonary Embolism Following Immunoglobulin
      Treatment in Pediatric Patient With Immune Thrombocytopenic Purpura.
AB  - Intravenous immunoglobulin (IVIG) is a widely used agent as the first choice of
      treatment of immune thrombocytopenic purpura (ITP). IVIG has several side
      effects, but it is a relatively safe treatment. Life-threatening thrombosis has
      been reported in adults and rarely in children. We report a case of a 14-year-old
      boy with dural venous sinus thrombosis and pulmonary embolism after treatment
      with IVIG for ITP. The patient was treated with low-molecular-weight heparin
      followed by warfarin and the symptoms were recovered. If a patient with ITP shows
      mental change or respiratory difficulty, we should consider thrombosis as well as
      hemorrhage.

PMID- 29068870
TI  - Multiple tissue methylation analysis of HTR2A exon I in suicidal behavior.
AB  - OBJECTIVE: The main aim of the current study was to investigate epigenetic
      alterations in serotonin 2A receptor (HTR2A) exon I CpG sites as possible risk
      factors for suicidal behavior. We also aimed to analyze the epigenetic
      alterations in two different tissues as epigenetic mechanisms are tissue
      specific. These epigenetic changes may lead to a better prediction of suicidal
      behavior. METHODS: Direct CpG methylation analysis was carried out on genomic DNA
      from the saliva of 20 schizophrenia suicide attempters and 27 non-attempters, and
      from post-mortem brain tissues of nine suicide victims and 11 controls. We used
      bisulfite pyrosequencing to assess the contributions of six CpG sites including
      the rs6313 (C102T) site in the first exon of HTR2A in suicide attempters and
      suicide victims. RESULTS: DNA methylation analysis did not find a significant
      difference in CpG methylation between suicide attempters and non-attempters
      (P=0.759) or between suicide victims and controls (P=0.189). We found a strong
      positive correlation between CpG methylation levels in blood and saliva (r=0.547,
      P<0.001). DISCUSSION: DNA methylation analysis confirmed that the overall
      methylation level of HTR2A exon I was around 80% for DNA extracted from saliva
      and almost 30% in the frontal cortex DNA. The results of this investigation do
      not support the evidence that methylation analysis of the HTR2A may be useful for
      investigating the epigenetic factors involved in suicidal behavior.

PMID- 29068871
TI  - ANK3 gene polymorphisms and bipolar disorder: a meta-analysis.
AB  - OBJECTIVE: Converging evidence has suggested ankyrin 3 (ANK3) as a risk gene for
      bipolar disorder (BD). However, association studies investigating its genetic
      variants and BD susceptibility have reported inconsistent results. In the present
      meta-analysis, we aimed to establish whether ANK3 single nucleotide polymorphisms
      (SNPs) confer increased risk for BD. METHODS: PubMed, Medline, PsycINFO, Embase,
      and Scopus were searched for literature published up to January 2017. Fourteen
      case-control studies met our eligibility criteria. We targeted ANK3 SNPs that
      have been reported by three or more studies to be included in the current meta
      analysis, resulting in a final list of four SNPs: rs10994336, rs9804190,
      rs10994397, and rs1938526. Odds ratios (ORs) for the allele model were calculated
      using a random effect model as a measure of association. Additional experimental
      characteristics and between-study heterogeneity were explored using sensitivity
      test, subgroup analysis, and meta-regression techniques. Publication bias was
      also assessed using Egger's test and rank correlation test. RESULTS: Overall, a
      significant association was found between BD and rs10994336 (OR=1.18; 95%
      confidence interval: 1.06-1.31; P=0.0027) as well as rs1938526 (OR=1.16; 95%
      confidence interval: 1.06-1.28; P=0.0016). Subsequent sensitivity analysis and
      publication bias test reaffirmed the stability and consistency of these results.
      CONCLUSION: The current meta-analysis provides corroborating evidence suggesting
      two ANK3 SNPs are associated with an increased susceptibility for developing BD.
      However, broader coverage is needed on less explored SNPs to further elucidate
      the genetic effect of other ANK3 variants that may harbor potential BD risk.

PMID- 29068872
TI  - Dopaminergic tone does not influence pain levels during placebo interventions in
      patients with chronic neuropathic pain.
AB  - Placebo effects have been reported in patients with chronic neuropathic pain.
      Expected pain levels and positive emotions are involved in the observed pain
      relief, but the underlying neurobiology is largely unknown. Patients with
      neuropathic pain are highly motivated for pain relief, and as motivational
      factors such as expectations of reward, as well as pain processing in itself, are
      related to the dopaminergic system, it can be speculated that dopamine release
      contributes to placebo effects in neuropathic pain. Nineteen patients with
      neuropathic pain after thoracic surgery were tested during a placebo intervention
      consisting of open and hidden applications of the pain-relieving agent lidocaine
      (2 mL) and no treatment. The dopamine antagonist haloperidol (2 mg) and the
      agonist levodopa/carbidopa (100/25 mg) were administered to test the involvement
      of dopamine. Expected pain levels, desire for pain relief, and ongoing and evoked
      pain were assessed on mechanical visual analog scales (0-10). Significant placebo
      effects on ongoing (P <= 0.003) and evoked (P <= 0.002) pain were observed.
      Expectancy and desire accounted for up to 41.2% and 71.5% of the variance in
      ongoing and evoked pain, respectively, after the open application of lidocaine.
      We found no evidence for an effect of haloperidol and levodopa/carbidopa on
      neuropathic pain levels (P = 0.071-0.963). Dopamine seemed to influence the
      levels of expectancy and desire, yet there was no evidence for indirect or
      interaction effects on the placebo effect. This is the first study to suggest
      that dopamine does not contribute to placebo effects in chronic neuropathic pain.

PMID- 29068874
TI  - Prevalence of nonaccidental trauma among children at American College of Surgeons
      verified pediatric trauma centers.
AB  - BACKGROUND: Child abuse remains a national epidemic that has detrimental effects
      if unnoticed in the clinical setting. Extreme cases of child abuse, or
      nonaccidental trauma (NAT), have large financial burdens associated with them due
      to treatment costs and long-term effects of abuse. Clinicians who have additional
      training and experience with pediatric trauma are better equipped to detect signs
      of NAT and have more experience reporting it. This additional training and
      experience can be measured by using the American College of Surgeons (ACS)
      Pediatric Trauma verification. It is hypothesized that ACS-verified pediatric
      trauma centers (vPTCs) have an increased prevalence of NAT because of this
      additional experience and training relative to non-ACS vPTCs. METHODS: The
      National Trauma Data Bank, for the years 2007 to 2014, was utilized to compare
      the prevalence of NAT between ACS vPTCs relative to non-ACS vPTCs to produce both
      crude and Injury Severity Score adjusted prevalence ratio estimates. RESULTS: The
      majority of NAT cases across all hospitals were male (58.3%). The mean age of the
      NAT cases was 2.3 years with a mean Injury Severity Score (ISS) of 11.1. The most
      common payment method was Medicaid (64.4%). The prevalence of NAT was 1.82 (1.74
      1.90) times higher among ACS vPTCs and 1.81 (1.73-1.90) after adjusting for ISS.
      CONCLUSIONS: The greater prevalence of NAT at vPTCs likely represents a more
      accurate measure of NAT among pediatric trauma patients, likely due to more
      experience and training of clinicians. LEVEL OF EVIDENCE:
      Prognostic/Epidemiological, Level II.

PMID- 29068873
TI  - Expanding the scope of quality measurement in surgery to include nonoperative
      care: Results from the American College of Surgeons National Surgical Quality
      Improvement Program emergency general surgery pilot.
AB  - BACKGROUND: Patients managed nonoperatively have been excluded from risk-adjusted
      benchmarking programs, including the American College of Surgeons (ACS) National
      Surgical Quality Improvement Program (NSQIP). Consequently, optimal performance
      evaluation is not possible for specialties like emergency general surgery (EGS)
      where nonoperative management is common. We developed a multi-institutional EGS
      clinical data registry within ACS NSQIP that includes patients managed
      nonoperatively to evaluate variability in nonoperative care across hospitals and
      identify gaps in performance assessment that occur when only operative cases are
      considered. METHODS: Using ACS NSQIP infrastructure and methodology, surgical
      consultations for acute appendicitis, acute cholecystitis, and small bowel
      obstruction (SBO) were sampled at 13 hospitals that volunteered to participate in
      the EGS clinical data registry. Standard NSQIP variables and 16 EGS-specific
      variables were abstracted with 30-day follow-up. To determine the influence of
      complications in nonoperative patients, rates of adverse outcomes were
      identified, and hospitals were ranked by performance with and then without
      including nonoperative cases. RESULTS: Two thousand ninety-one patients with EGS
      diagnoses were included, 46.6% with appendicitis, 24.3% with cholecystitis, and
      29.1% with SBO. The overall rate of nonoperative management was 27.4%, 6.6% for
      appendicitis, 16.5% for cholecystitis, and 69.9% for SBO. Despite comprising only
      27.4% of patients in the EGS pilot, nonoperative management accounted for 67.7%
      of deaths, 34.3% of serious morbidities, and 41.8% of hospital readmissions.
      After adjusting for patient characteristics and hospital diagnosis mix, addition
      of nonoperative management to hospital performance assessment resulted in 12 of
      13 hospitals changing performance rank, with four hospitals changing by three or
      more positions. CONCLUSION: This study identifies a gap in performance evaluation
      when nonoperative patients are excluded from surgical quality assessment and
      demonstrates the feasibility of incorporating nonoperative care into existing
      surgical quality initiatives. Broadening the scope of hospital performance
      assessment to include nonoperative management creates an opportunity to improve
      the care of all surgical patients, not just those who have an operation. LEVEL OF
      EVIDENCE: Care management, level IV; Epidemiologic, level III.

PMID- 29068875
TI  - The role of splenic angioembolization as an adjunct to nonoperative management of
      blunt splenic injuries: A systematic review and meta-analysis.
AB  - BACKGROUND: Nonoperative management (NOM) of hemodynamically normal patients with
      blunt splenic injury (BSI) is the standard of care. Guidelines recommend
      additional splenic angioembolization (SAE) in patients with American Association
      for the Surgery of Trauma (AAST) Grade IV and Grade V BSI, but the role of SAE in
      Grade III injuries is unclear and controversial. The aim of this systematic
      review was to compare the safety and effectiveness of SAE as an adjunct to NOM
      versus NOM alone in adults with BSI. METHODS: A systematic literature search
      (Medline, Embase, and CINAHL) was performed to identify original studies that
      compared outcomes in adult BSI patients treated with SAE or NOM alone. Primary
      outcome was failure of NOM. Secondary outcomes included morbidity, mortality,
      hospital length of stay, and transfusion requirements. Bayesian meta-analyses
      were used to calculate an absolute (risk difference) and relative (risk ratio
      [RR]) measure of treatment effect for each outcome. RESULTS: Twenty-three studies
      (6,684 patients) were included. For Grades I to V combined, there was no
      difference in NOM failure rate (SAE, 8.6% vs NOM, 7.7%; RR, 1.09 [0.80-1.51]; p =
      0.28), mortality (SAE, 4.8% vs NOM, 5.8%; RR, 0.82 [0.45-1.31]; p = 0.81),
      hospital length of stay (11.3 vs 9.5 days; p = 0.06), or blood transfusion
      requirements (1.8 vs 1.7 units; p = 0.47) between patients treated with SAE and
      those treated with NOM alone. However, morbidity was significantly higher in
      patients treated with SAE (SAE, 38.1% vs NOM, 18.6%; RR, 1.83 [1.20-2.66]; p <
      0.01). When stratified by grade of splenic injury, SAE significantly reduced the
      failure rate of NOM in patients with Grade IV and Grade V splenic injuries but
      had minimal effect in those with Grade I to Grade III injuries. CONCLUSION:
      Splenic angioembolization should be strongly considered as an adjunct to NOM in
      patients with AAST Grade IV and Grade V BSI but should not be routinely
      recommended in patients with AAST Grade I to Grade III injuries. LEVEL OF
      EVIDENCE: Systematic review and meta-analysis, level III.

PMID- 29068876
TI  - Shootout at the O.K. Corral-History Revisited.

PMID- 29068877
TI  - Featured Articles for CME Credit November 2017.

PMID- 29068879
TI  - Long-Term Sustainability of Functional Improvement Following Central Corpectomy
      for Cervical Spondylotic Myelopathy and Ossification of Posterior Longitudinal
      Ligament.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To examine predictors of long-term
      outcome and sustainability of initial functional improvement in patients
      undergoing corpectomy for cervical spondylotic myelopathy (CSM) or ossification
      of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: There
      are limited data on the predictors of outcome and sustainability of initial
      functional improvement on long-term follow-up after cervical corpectomy. METHODS:
      We studied the functional outcome at more than 1-year follow-up after central
      corpectomy in 352 patients with CSM or OPLL. Functional status was evaluated with
      the Nurick grading system. Analysis was directed at identifying factors
      associated with both improvement in functional status and the achievement of a
      "cure" (improvement to a follow-up Nurick grade of 0 or 1). A survival analysis
      was performed to identify factors associated with sustained functional
      improvement in patients with serial follow-up evaluations. RESULTS: Nurick grade
      improved from 3.2 +/- 0.1 to 1.9 +/- 0.1 over a mean follow-up period of 57.1
      months (range 12-228 mo). On multivariate analysis, age >=50 years (P = 0.008)
      and symptom duration >=1 year (P < 0.001) were negatively associated with
      functional improvement by >=1 Nurick grade. Independent factors negatively
      associated with "cure" after surgery included age 50 years or older (P = 0.005),
      preoperative Nurick grade of 4 or higher (P < 0.001) and symptom duration of 1 or
      more years (P < 0.001). Early improvement in functional status was maintained in
      90.5% and 76.3% of patients at 5 and 10 years follow-up, respectively. On
      survival analysis, patients with shorter preoperative symptom duration (<1 yr)
      were more likely to demonstrate sustained improvement in functional status after
      surgery (P = 0.022). CONCLUSION: Initial gains in functional status after central
      corpectomy for CSM and OPLL are maintained in more than 75% of patients at 10
      years after surgery. Overall, the most favorable long-term outcomes are achieved
      in younger patients who present early and with good preoperative functional
      status. LEVEL OF EVIDENCE: 4.

PMID- 29068880
TI  - Quantitative Magnetization Transfer MRI Measurements of the Anterior Spinal Cord
      Region are Associated With Clinical Outcomes in Cervical Spondylotic Myelopathy.
AB  - STUDY DESIGN: A case-control study. OBJECTIVE: The aim of this study was to
      understand the role of magnetization transfer ratio (MTR) in identifying patients
      with clinically significant myelopathy and disability. SUMMARY OF BACKGROUND
      DATA: MTR is a quantitative measure that correlates with myelin loss and neural
      tissue destruction in a variety of neurological diseases. However, the usefulness
      of MTR in patients with cervical spondylotic myelopathy (CSM) has not been
      examined. METHODS: We prospectively enrolled seven CSM patients and seven age
      matched controls to undergo magnetic resonance imaging (MRI) of the cervical
      spine. Nurick, Neck Disability Index (NDI), and modified Japanese Orthopedic
      Association (mJOA) scores were collected for all patients. Clinical hyperreflexia
      was tested at the MCP joint, using a six-axis load cell. Reflex was simulated by
      quickly moving the joint from maximum flexion to maximum extension (300 degrees
      /second). Anterior, lateral, and posterior cord MTR measurements were compared
      with clinical outcomes. RESULTS: Compared with controls, CSM patients had lower
      anterior cord MTR (38.29 vs. 29.97, Delta = -8.314, P = 0.0022), and equivalent
      posterior cord (P = 0.2896) and lateral cord (P = 0.3062) MTR. Higher Nurick
      scores were associated with lower anterior cord MTR (P = 0.0205), but not lateral
      cord (P = 0.5446) or posterior cord MTR (P = 0.1222). Lower mJOA was associated
      with lower anterior cord MTR (P = 0.0090), but not lateral cord (P = 0.4864) or
      posterior cord MTR (P = 0.4819). There was no association between NDI and MTR of
      the anterior (P = 0.4351), lateral (P = 0.7557), or posterior cord (P = 0.9171).
      There was a linear relationship between hyperreflexia and anterior cord MTR
      (slope = -117.3, R = 0.6598, P = 0.0379), but not lateral cord (P = 0.1906, R =
      0.4511) or posterior cord (P = 0.2577, R = 0.3957) MTR. CONCLUSION: Anterior cord
      MTR correlates with clinical outcomes as measured by mJOA index, Nurick score,
      and quantitative hyperreflexia, and could play a role in the preoperative
      assessment of CSM. LEVEL OF EVIDENCE: 2.

PMID- 29068881
TI  - Correction of Paradoxical Ribcage Motion in Scoliosis by Noninvasive Ventilation.
AB  - STUDY DESIGN: Observational study of ribcage motion in scoliosis. OBJECTIVE: To
      see whether noninvasive ventilation corrected paradoxical inward motion of the
      ribs during inspiration. SUMMARY OF BACKGROUND DATA: Paradoxical inward motion of
      the ribs is observed after rib fractures, low cervical cord injury, and in
      chronic obstructive pulmonary disease. It is not well recognized in scoliosis and
      the mechanism in this group has not been studied. METHODS: Linearized
      magnetometers were used to measure the diameter of the ribcage. Changes in
      diameter during tidal breathing were recorded during spontaneous ventilation and
      noninvasive ventilation in 10 subjects with idiopathic or congenital thoracic
      scoliosis. RESULTS: During spontaneous breathing, the median change in ribcage
      diameter during inspiration was -1.5 (range -2.3 to -0.8) cm. The median change
      in ribcage diameter during noninvasive ventilation was +0.5 (range -1.1 to +1.2)
      cm. Noninvasive ventilation improved paradoxical motion in all subjects,
      completely correcting it in six. CONCLUSION: Paradoxical inward motion of the
      ribcage is seen in some subjects with severe scoliosis. This abnormal motion is
      improved or abolished by noninvasive ventilation. Since noninvasive ventilation
      takes over the work of breathing from the respiratory muscles, we suggest that
      inspiratory muscle contraction causes distortion of part of the ribcage in
      scoliosis, probably because of the abnormal orientation of diaphragmatic muscle
      fibers. LEVEL OF EVIDENCE: 2.

PMID- 29068882
TI  - The Use of Low-Profile Silicone Breast Implants in Male Breast Reconstruction.

PMID- 29068883
TI  - Reply: Fat Grafting in the Hollow Upper Eyelids and Volumetric Upper
      Blepharoplasty.

PMID- 29068884
TI  - Managing Venous Hypertension in Vascularized Omentum Lymphatic Transplant:
      Restoring Bidirectional Venous Drainage.

PMID- 29068885
TI  - May One-Cup-Size Increase Be Used as the Clinical Reference?

PMID- 29068886
TI  - Reply: Terminology in Transgender Patient Care.

PMID- 29068888
TI  - Terminology in Transgender Patient Care.

PMID- 29068887
TI  - Subfascial Primary Breast Augmentation with Fat Grafting: A Review of 156 Cases.

PMID- 29068889
TI  - The Need for a Low Cost 3D Scanner.

PMID- 29068890
TI  - Software-Based Three-Dimensional Surface Imaging and Scanning in Plastic Surgery.

PMID- 29068891
TI  - Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma Proliferation.

PMID- 29068892
TI  - Reply: Urinary Excretion of MicroRNA-126 Is a Biomarker for Hemangioma
      Proliferation.

PMID- 29068893
TI  - Reply: Subfascial Primary Breast Augmentation with Fat Grafting: A Review of 156
      Cases.

PMID- 29068894
TI  - "3D computer-assisted three-layered models of the face".

PMID- 29068895
TI  - A Prospective Randomized Trial of the Efficacy of Fibrin Glue, Triamcinolone
      Acetonide, and Quilting Sutures in Seroma Prevention after Latissimus Dorsi
      Breast Reconstruction.

PMID- 29068896
TI  - Updates in Head and Neck Reconstruction.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Have a basic understanding of virtual planning, rapid prototype modeling,
      three-dimensional printing, and computer-assisted design and manufacture. 2.
      Understand the principles of combining virtual planning and vascular mapping. 3.
      Understand principles of flap choice and design in preoperative planning of free
      osteocutaneous flaps in mandible and midface reconstruction. 4. Discuss
      advantages and disadvantages of computer-assisted design and manufacture in
      reconstruction of advanced oncologic mandible and midface defects. SUMMARY:
      Virtual planning and rapid prototype modeling are increasingly used in head and
      neck reconstruction with the aim of achieving superior surgical outcomes in
      functionally and aesthetically critical areas of the head and neck compared with
      conventional reconstruction. The reconstructive surgeon must be able to
      understand this rapidly-advancing technology, along with its advantages and
      disadvantages. There is no limit to the degree to which patient-specific data may
      be integrated into the virtual planning process. For example, vascular mapping
      can be incorporated into virtual planning of mandible or midface reconstruction.
      Representative mandible and midface cases are presented to illustrate the process
      of virtual planning. Although virtual planning has become helpful in head and
      neck reconstruction, its routine use may be limited by logistic challenges,
      increased acquisition costs, and limited flexibility for intraoperative
      modifications. Nevertheless, the authors believe that the superior functional and
      aesthetic results realized with virtual planning outweigh the limitations.

PMID- 29068897
TI  - Should Immediate Autologous Breast Reconstruction Be Considered in Women Who
      Require Postmastectomy Radiation Therapy? A Prospective Analysis of Outcomes.

PMID- 29068898
TI  - Comparison of Outcomes with Tissue Expander, Immediate Implant, and Autologous
      Breast Reconstruction in Greater Than 1000 Nipple-Sparing Mastectomies.

PMID- 29068899
TI  - Fat Grafting in the Hollow Upper Eyelids and Volumetric Upper Blepharoplasty.

PMID- 29068900
TI  - Reply: Comparison of Outcomes with Tissue Expander, Immediate Implant, and
      Autologous Breast Reconstruction in Greater Than 1000 Nipple-Sparing
      Mastectomies.

PMID- 29068901
TI  - Developing, Conducting, and Publishing Appropriate Systematic Review and Meta
      Analysis Articles.
AB  - The volume of medical literature is growing at a rate that renders decision
      making difficult without specialized summary tools. Systematic reviews and meta
      analyses are important research instruments used to condense and clarify a broad
      scope of information into manageable summaries. When used effectively, these
      reports can pool cumulative data across primary studies, formulate clinical
      guidelines, and guide future research endeavors. However, errors in study design
      can result in ineffective or misleading analyses. This article presents the
      appropriate uses for systematic review and meta-analysis by introducing a
      framework for creating summary studies, and supplying specific examples of
      pitfalls in study design and execution.

PMID- 29068902
TI  - Optimization of Surgical Outcome in Lower Extremity Nerve Decompression Surgery.
AB  - BACKGROUND: There is still debate regarding whether the surgical release of
      entrapped lower extremity nerves reduces complaints of associated neuropathy and
      results in gain of sensory function. The aim of this study was to investigate
      which factors are associated with a favorable surgical outcome, by follow-up of
      patients previously participating in a randomized controlled trial. METHODS: The
      authors evaluated the 5-year follow-up of diabetic patients previously
      participating in the Lower Extremity Nerve Entrapment Study (LENS). Visual
      analogue pain scores, satisfaction, complaints, quality of life (i.e., 36
      Question Short-Form Health Survey and EuroQol 5 Dimensions instrument), sensory
      function, and incident ulceration and amputation were assessed. Differences
      between patients who underwent unilateral versus bilateral decompressions were
      investigated. RESULTS: Thirty-one of the original 42 LENS participants were
      measured, of which eight patients underwent additional decompression of the
      contralateral leg, after 12-month LENS follow-up. At 5 years, bilateral surgical
      patients (n = 8) had significantly lower pain scores and higher quality of life
      compared with unilateral surgical patients (n = 23), were younger, had a lower
      age when diagnosed with diabetes, and had a lower body mass index at baseline.
      Pain scores of the additional decompressed leg decreased in a manner similar to
      that of the initial decompressed leg during follow-up. Patients with severe
      preoperative sensory loss did worse; 41.2 percent of the LENS Follow-Up Study
      subjects underwent or considered undergoing contralateral surgery. CONCLUSION:
      The authors' results suggest that the beneficial effects of lower extremity nerve
      decompression surgery are reserved for a select group of patients, of which
      preoperative nerve damage, age, duration of diabetes, and body mass index are
      important effect modifiers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 29068903
TI  - Redefining the Rectus Sheath: Implications for Abdominal Wall Repair.
AB  - BACKGROUND: The abdominal wall is frequently manipulated in a variety of
      reconstructive procedures, and its anatomy is well described. The authors'
      clinical observations, however, contradict the standard depiction of the
      components of the abdominal wall at various levels-particularly regarding the
      course of the transversus abdominis muscle. Therefore, the authors sought to
      characterize the components of the rectus sheath at various surgical landmarks to
      define anatomic points important to abdominal wall repair. METHODS: The authors
      analyzed the abdominal computed tomographic studies of 100 healthy, young (age,
      18 to 35 years; body mass index, 20 to 40 kg/m) patients with suspected renal
      calculi. Coordinates of key landmarks were recorded at vertebral levels T12 to L5
      using a specially designed computer program that scaled all values and calculated
      distances between various points. RESULTS: All subjects had significant presence
      of the transversus abdominis within the rectus sheath (the overlap between the
      abdominis rectus and transversus abdominis muscles) at the costal margin plane
      (T12-L1, 4.2 cm). Ninety-nine percent had transversus abdominis presence within
      the rectus sheath at L1-L2 (3.2 cm), 86 percent at the level of the twelfth rib
      (L2-L3, 1.4 cm), 36 percent at the umbilicus (L3-L4), and 2 percent slightly
      above the posterosuperior iliac spine (L5-S1). CONCLUSIONS: These findings
      contradict classic teachings of abdominal wall structure and highlight the need
      for a cautious revisiting of the various permutations of component separation,
      particularly posterior component release. Furthermore, these anatomical landmarks
      may help predict the development or recurrence of ventral hernias, thus guiding
      patient selection and informing surgical technique.

PMID- 29068904
TI  - Impact of Nursing Home Palliative Care Teams on End-of-Life Outcomes: A
      Randomized Controlled Trial.
AB  - BACKGROUND: Deficits in end-of-life care in nursing homes (NHs) are reported, but
      the impact of palliative care teams (PCTeams) on resident outcomes remains
      largely untested. OBJECTIVE: Test the impact of PCTeams on end-of-life outcomes.
      RESEARCH DESIGN: Multicomponent strategy employing a randomized, 2-arm controlled
      trial with a difference-in-difference analysis, and a nonrandomized second
      control group to assess the intervention's placebo effect. SUBJECTS: In all, 25
      New York State NHs completed the trial (5830 decedent residents) and 609 NHs were
      in the nonrandomized group (119,486 decedents). MEASURES: Four risk-adjusted
      outcome measures: place of death, number of hospitalizations, self-reported
      moderate-to-severe pain, and depressive symptoms. The Minimum Data Set, vital
      status files, staff surveys, and in-depth interviews were employed. For each
      outcome, a difference-in-difference model compared the pre-post intervention
      periods using logistic and Poisson regressions. RESULTS: Overall, we found no
      statistically significant effect of the intervention. However, independent
      analysis of the interview data found that only 6 of the 14 treatment facilities
      had continuously working PCTeams throughout the study period. Decedents in homes
      with working teams had significant reductions in the odds of in-hospital death
      compared to the other treatment [odds ratio (OR), 0.400; P<0.001), control (OR,
      0.482; P<0.05), and nonrandomized control NHs (0.581; P<0.01). Decedents in these
      NHs had reduced rates of depressive symptoms (OR, 0.191; P<=0.01), but not pain
      or hospitalizations. CONCLUSIONS: The intervention was not equally effective for
      all outcomes and facilities. As homes vary in their ability to adopt new care
      practices, and in their capacity to sustain them, reforms to create the
      environment in which effective palliative care can become broadly implemented are
      needed.

PMID- 29068905
TI  - What Role Does Efficiency Play in Understanding the Relationship Between Cost and
      Quality in Physician Organizations?
AB  - BACKGROUND: The belief that there is inefficiency, or the potential to improve
      patient health at current levels of spending, is driving the push for greater
      value in health care. Previous studies demonstrate overuse of a narrow set of
      services, suggesting provider inefficiency, but existing studies neither quantify
      inefficiency more broadly nor assess its variation across physician organizations
      (POs). DATA AND METHODS: We used data on quality of care and total cost of care
      from 129 California POs participating in a statewide value-based pay-for
      performance program. We estimated a production function with quality as the
      output and cost as the input, using a stochastic frontier model, to develop a
      measure of relative efficiency for each PO. To validate the efficiency measure,
      we examined correlations of PO efficiency estimates with indicators representing
      overuse of services. RESULTS: The estimated production function showed that PO
      quality was positively associated with costs, although there were diminishing
      marginal returns to spending. A certain minimum level of spending was associated
      with high quality even among efficient POs. Most strikingly, however, POs had
      substantial variation in efficiency, producing widely differing levels of quality
      for the same cost. CONCLUSIONS: Differences among POs in the efficiency with
      which they produce quality suggest opportunities for improvements in care
      delivery that increase quality without increasing spending.

PMID- 29068907
TI  - Diagnosis-based Cost Groups in the Dutch Risk-equalization Model: Effects of
      Clustering Diagnoses and of Allowing Patients to be Classified into Multiple Risk
      classes.
AB  - BACKGROUND: The risk-equalization (RE) model in the Dutch health insurance market
      has evolved to a sophisticated model containing direct proxies for health.
      However, it still has important imperfections, leaving incentives for risk
      selection. This paper focuses on refining an important health-based risk-adjuster
      in this model: the diagnosis-based costs groups (DCGs). The current (2017) DCGs
      are calibrated on "old" data of 2011/2012, are mutually exclusive, and are
      essentially clusters of about 200 diagnosis-groups ("dxgroups"). METHODS:
      Hospital claims data (2013), administrative data (2014) on costs and risk
      characteristics for the entire Dutch population (N~16.9 million), and health
      survey data (2012, N~387,000) are used. The survey data are used to identify
      subgroups of individuals in poor or in good health. The claims and administrative
      data are used to develop alternative DCG-modalities to examine the impact on
      individual-level and group-level fit of recalibrating the DCGs based on new data,
      of allowing patients to be classified in multiple DCGs, and of refraining from
      clustering. RESULTS: Recalibrating the DCGs and allowing enrolees to be
      classified into multiple DCGs lead to nontrivial improvements in individual-level
      and group-level fit (especially for cancer patients and people with comorbid
      conditions). The improvement resulting from refraining from clustering does not
      seem to justify the increase in model complexity this would entail. CONCLUSIONS:
      The performance of the sophisticated Dutch RE-model can be improved by allowing
      classification in multiple (clustered) DCGs and using new data. Irrespective of
      the modality used, however, various subgroups remain significantly
      undercompensated. Further improvement of the RE-model merits high priority.

PMID- 29068906
TI  - Regional Medicare Expenditures and Survival Among Older Women With Localized
      Breast Cancer.
AB  - BACKGROUND: Despite evidence on large variation in breast cancer expenditures
      across geographic regions, there is little understanding about the association
      between expenditures and patient outcomes. OBJECTIVES: To examine whether
      Medicare beneficiaries with nonmetastatic breast cancer living in regions with
      higher cancer-related expenditures had better survival. RESEARCH DESIGN: A
      retrospective cohort study of women with localized breast cancer from the
      Surveillance, Epidemiology, and End Results-Medicare linked database. Hospital
      referral regions (HRR) were categorized into quintiles based on risk-standardized
      per patient Medicare expenditures on initial phase of breast cancer care.
      Hierarchical generalized linear models were estimated to examine the association
      between patients' HRR quintile and survival. SUBJECTS: In total, 12,610 Medicare
      beneficiaries diagnosed with stage II-III breast cancer during 2005-2008 who
      underwent surgery. MEASURES: Outcome measures for our analysis were 3- and 5-year
      overall survival. RESULTS: Risk-standardized per patient Medicare expenditures on
      initial phase of breast cancer care ranged from $13,338 to $26,831 across the
      HRRs. Unadjusted 3- and 5-year survival varied from 66.7% to 92.2% and 50.0% to
      84.0%, respectively, across the HRRs, but there was no significant association
      between HRR quintile and survival in bivariate analysis (P=0.08 and 0.28,
      respectively). After adjustment for sociodemographic and clinical
      characteristics, quintiles of regional cancer expenditures remained unassociated
      with patients' 3-year (P=0.35) and 5-year survival (P=0.20). Further analysis
      adjusting for treatment factors (surgery type and receipt of radiation and
      systemic therapy) and stratifying by cancer stage showed similar results.
      CONCLUSIONS: For Medicare beneficiaries with nonmetastatic breast cancer,
      residence in regions with higher breast cancer-related expenditures was not
      associated with better survival. More attention to value in breast cancer care is
      warranted.

PMID- 29068908
TI  - Medicaid Coverage Expansions and Cigarette Smoking Cessation Among Low-income
      Adults.
AB  - INTRODUCTION: Expanding Medicaid coverage to low-income adults may have increased
      smoking cessation through improved access to evidence-based treatments. Our study
      sought to determine if states' decisions to expand Medicaid increased recent
      smoking cessation. METHODS: Using pooled cross-sectional data from the Behavioral
      Risk Factor Surveillance Survey for the years 2011-2015, we examined the
      association between state Medicaid coverage and the probability of recent smoking
      cessation among low-income adults without dependent children who were current or
      former smokers (n=36,083). We used difference-in-differences estimation to
      examine the effects of Medicaid coverage on smoking cessation, comparing low
      income adult smokers in states with Medicaid coverage to comparable adults in
      states without Medicaid coverage, with ages 18-64 years to those ages 65 years
      and above. Analyses were conducted for the full sample and stratified by sex.
      RESULTS: Residence in a state with Medicaid coverage among low-income adult
      smokers ages 18-64 years was associated with an increase in recent smoking
      cessation of 2.1 percentage points (95% confidence interval, 0.25-3.9). In the
      comparison group of individuals ages 65 years and above, residence in a state
      with Medicaid coverage expansion was not associated with a change in recent
      smoking cessation (-0.1 percentage point, 95% confidence interval, -2.1 to 1.8).
      Similar increases in smoking cessation among those ages 18-64 years were
      estimated for females and males (1.9 and 2.2 percentage point, respectively).
      CONCLUSION: Findings are consistent with the hypothesis that Medicaid coverage
      expansions may have increased smoking cessation among low-income adults without
      dependent children via greater access to preventive health care services,
      including evidence-based smoking cessation services.

PMID- 29068909
TI  - Contemporary Postnatal Incidence of Acquiring Acute Myocarditis by Age 15 Years
      and the Outcomes From a Nationwide Birth Cohort.
AB  - OBJECTIVES: Acute myocarditis can be lethal, but the incidence remains unclear
      because of its wide manifestation spectrum. We investigated the postnatal
      incidence of acute myocarditis and risk factors for morbidity and mortality.
      DESIGN: Retrospective derived birth cohort study. SETTING: Taiwan National Health
      Insurance Database for the period 2000-2014. PATIENTS: Children born between 2000
      and 2009 with complete postnatal medical care data for at least 5 years.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From among 2,150,590 live
      births, we identified 965 patients (54.8% male) admitted with the diagnosis of
      acute myocarditis, accounting for an overall incidence of 0.45/1,000. The
      cumulative incidence rates were 0.19/1,000, 0.38/1,000, 0.42/1,000, and
      0.48/1,000 by ages 1, 5, 10, and 15 years, respectively. Male predominance was
      noted in infants and school age children (age group 6-14 yr). Arrhythmias,
      including tachyarrhythmia (4.8%) and bradyarrhythmia (1.1%), occurred in 56
      patients. Extracorporeal membrane oxygenation support was provided to 62 patients
      (6.4%) and additional left ventricular assist devices in six of them. The
      mortality at discharge was 6.3%. The presence of ventricular tachyarrhythmia,
      bradyarrhythmia, and an onset at school age (6-14 yr) were associated with
      increased odds for the need for extracorporeal membrane oxygenation, which was
      the only predictor for mortality at discharge (hazard ratio, 7.85; 95% CI, 3.74
      9.29). In patients who survived the acute myocarditis, late mortality was
      relatively low (36/904 = 4.0%). The overall survival of children with acute
      myocarditis were 90.9%, 90.3%, and 89.8% by the intervals of 1, 5, and 10 years
      after the myocarditis, respectively. CONCLUSIONS: This birth cohort study
      determined the cumulative incidence of acute myocarditis for neonates by 15 years
      old to be one in 2,105. In an era of extracorporeal membrane oxygenation, the
      need of extracorporeal membrane oxygenation may reflect the severity of acute
      myocarditis and predict its outcome.

PMID- 29068911
TI  - ACQUIRED VITELLIFORM LESIONS THAT RESPOND TO IMMUNE SUPPRESSION IN A PATIENT WITH
      SARCOIDOSIS.
AB  - PURPOSE: To describe a patient with sarcoid uveitis who developed bilateral
      vitelliform lesions with subretinal fluid that responded to immune suppression on
      three occasions. METHODS: Chart review was performed on a single patient to
      collect all relevant clinical information and diagnostic imaging. RESULTS: A case
      of sarcoidosis with acquired vitelliform lesions is described. CONCLUSION:
      Patients with ocular sarcoidosis can rarely develop vitelliform lesions. Our
      patient responded to systemic immune suppression.

PMID- 29068910
TI  - Neutrophil Phenotype Correlates With Postoperative Inflammatory Outcomes in
      Infants Undergoing Cardiopulmonary Bypass.
AB  - OBJECTIVES: Infants with congenital heart disease frequently require
      cardiopulmonary bypass, which causes systemic inflammation. The goal of this
      study was to determine if neutrophil phenotype and activation status predicts the
      development of inflammatory complications following cardiopulmonary bypass.
      DESIGN: Prospective cohort study. SETTING: Tertiary care PICU with postoperative
      cardiac care. PATIENTS: Thirty-seven patients 5 days to 10 months old with
      congenital heart disease requiring cardiopulmonary bypass. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Laboratory and clinical data collected included
      length of mechanical ventilation, acute kidney injury, and fluid overload.
      Neutrophils were isolated from whole blood at three time points surrounding
      cardiopulmonary bypass. Functional analyses included measurement of cell surface
      protein expression and nicotinamide adenine dinucleotide phosphate oxidase
      activity. Of all patients studied, 40.5% displayed priming of nicotinamide
      adenine dinucleotide phosphate oxidase activity in response to N-formyl-Met-Leu
      Phe stimulation 24 hours post cardiopulmonary bypass as compared to pre bypass.
      Neonates who received steroids prior to bypass demonstrated enhanced priming of
      nicotinamide adenine dinucleotide phosphate oxidase activity at 48 hours.
      Patients who displayed priming post cardiopulmonary bypass were 8.8 times more
      likely to develop severe acute kidney injury as compared to nonprimers. Up
      regulation of neutrophil surface CD11b levels pre- to postbypass occurred in
      51.4% of patients, but this measure of neutrophil priming was not associated with
      acute kidney injury. Subsequent analyses of the basal neutrophil phenotype
      revealed that those with higher basal CD11b expression were significantly less
      likely to develop acute kidney injury. CONCLUSIONS: Neutrophil priming occurs in
      a subset of infants undergoing cardiopulmonary bypass. Acute kidney injury was
      more frequent in those patients who displayed priming of nicotinamide adenine
      dinucleotide phosphate oxidase activity after cardiopulmonary bypass. This pilot
      study suggests that neutrophil phenotypic signature could be used to predict
      inflammatory organ dysfunction.

PMID- 29068912
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY TO DETECT MACULAR CAPILLARY ISCHEMIA IN
      PATIENTS WITH INNER RETINAL CHANGES AFTER RESOLVED DIABETIC MACULAR EDEMA.
AB  - PURPOSE: To compare foveal vascular anatomy between patients with and without
      disorganization of retinal inner layers (DRILs) after resolved diabetic macular
      edema using optical coherence tomography angiography (OCTA). METHODS: Twenty-four
      eyes of 21 age- and sex-matched patients with resolved diabetic macular edema
      were included in this retrospective, cross-sectional study. All eyes were imaged
      with enhanced high-definition line or cross-line structural B scans and 3 * 3-mm
      OCTA scans. Optical coherence tomography B scans were analyzed for the presence
      of DRIL, and based on this, eyes were classified as either DRIL present or DRIL
      absent. The foveal avascular zone area on OCTA was compared between patients with
      and without DRIL. The foveal avascular zone area was correlated with visual
      acuity. RESULTS: Nine eyes with DRIL and resolved diabetic macular edema were
      compared with 15 control eyes without DRIL and resolved diabetic macular edema.
      Area of ischemia on OCTA scans corresponded to the area of DRIL as determined on
      OCT B scans. The foveal avascular zone area in full retina as well as superficial
      and deep retinal plexuses OCTA slabs were significantly larger in patients with
      DRIL as compared to those without DRIL (P = 0.005, P < 0.001, and P = 0.004,
      respectively). The larger foveal avascular zone in full retinal segmentation (r =
      0.72, P = 0.03) and superficial plexus (r = 0.74, P = 0.02) were positively
      correlated with lower visual acuity. CONCLUSION: Optical coherence tomography
      angiography can visualize retinal ischemia in patients with and without DRIL.
      Correspondence of impaired blood flow with DRIL suggests that retinal ischemia
      and loss of normal vasculature contributes to DRIL.

PMID- 29068913
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH RETINITIS PIGMENTOSA.
AB  - PURPOSE: To evaluate the correlation between the flow density measured by optical
      coherence tomography angiography and functional parameters in patients with
      retinitis pigmentosa. METHODS: Twenty eyes of 20 patients with retinitis
      pigmentosa and 21 eyes of 21 healthy subjects were prospectively included in this
      study. Optical coherence tomography angiography was performed using RTVue XR
      Avanti with AngioVue (Optovue Inc). The macula was imaged with a 6 * 6-mm scan,
      whereas for the optic nerve head a 4.5 * 4.5-mm scan was taken. Visual acuity,
      visual field parameters (mean deviation and visual field index), full-field
      electroretinography, and multifocal electroretinography were tested for
      correlation with flow density data. RESULTS: The flow density (whole en face) in
      the superficial/deep retinal OCT angiograms and in the optical coherence
      tomography angiography of the optic nerve head was significantly lower in the
      retinitis pigmentosa group when compared with the control group (P < 0.001). The
      flow density in the superficial retinal OCT angiogram (fovea) correlated
      significantly with the visual acuity (rSpearman = -0.77, P < 0.001) and the
      visual field parameters (visual field index: rSpearman = 0.56, P = 0.01; mean
      deviation: rSpearman = 0.54, P = 0.01). CONCLUSION: Patients with retinitis
      pigmentosa show a decreased macular and optic nerve head perfusion compared with
      healthy subjects. The flow density measured using optical coherence tomography
      angiography correlated with subjective and objective functional parameters.

PMID- 29068914
TI  - COMPLIANCE AND ADHERENCE OF PATIENTS WITH DIABETIC MACULAR EDEMA TO INTRAVITREAL
      ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN DAILY PRACTICE.
AB  - PURPOSE: We assessed differences in compliance and adherence (lateness of
      patients, visual acuity, reasons for abstaining) between patients with diabetic
      macular edema (DME) and patients with age-related macular degeneration (AMD),
      both under anti-vascular endothelial growth factor therapy. METHODS: We included
      136 patients with DME (36% women, 65 years, 22 visits, 13.9 injections, and 29.9
      months of follow-up) and 109 patients with AMD (59% women, 76 years, 20 visits,
      14.7 injections, and 22.3 months of follow-up) (minimum follow-up of 12 months
      and at least 5 injections). We assessed missed appointments (lateness >14 days)
      and therapy break-offs (lateness >100 days). All delayed patients were called and
      interviewed for abstaining reasons. RESULTS: Forty-six percent of patients with
      DME and 22% of patients with AMD had at least one break-off. Thirty-five percent
      of patients with DME and 50% of patients with AMD were always on schedule. In
      patients with DME, there was significant correlation (P = 0.017) between the
      number of break-offs and change of visual acuity. In 60% DME and 38% AMD of break
      off cases, visual acuity was worse than the before break-off. The most common
      reason for abstaining was comorbidities (33% AMD and 20% DME). CONCLUSION: There
      are significant differences between patients with AMD and DME regarding
      compliance and adherence, which also affects outcome. Strategies to tie patients
      with DME to costly intravitreal therapy need to be developed to improve outcomes
      and efficacy.

PMID- 29068915
TI  - OCULAR MANIFESTATIONS OF SYSTEMIC AMYLOIDOSIS.
AB  - PURPOSE: To describe ophthalmic manifestations of systemic amyloidosis, a group
      of devastating conditions. METHODS: A retrospective chart review including
      patients who had ocular examinations at Mayo Clinic between January 1, 1985, and
      April 1, 2014, and a diagnosis of light-chain (AL), secondary (AA), or
      nontransthyretin familial amyloidosis was undertaken. Sixty-eight patients with
      AL amyloidosis, eight patients with AA amyloidosis, and five patients with
      nontransthyretin familial amyloidosis were included. RESULTS: Of 68 patients, 8
      patients (14 eyes) with AL amyloidosis had ocular involvement secondary to
      conjunctiva, temporal artery, extraocular muscle, trabecular meshwork, and
      cranial nerve deposition. One of the five patients with nontransthyretin familial
      amyloidosis had gelsolin-related corneal dystrophy. No patients with AA
      amyloidosis (n = 8) had ophthalmic manifestations. CONCLUSION: Systemic
      amyloidosis can lead to ocular morbidity. Patients with AL amyloidosis had
      involvement of the temporal artery, conjunctiva, extraocular muscles, trabecular
      meshwork, and cranial nerves. Those with gelsolin nontransthyretin familial
      amyloidosis were susceptible to corneal dystrophy. Patients with AA amyloidosis
      did not manifest ophthalmic involvement. Finally, if ocular amyloidosis is
      detected, patients should be referred for systemic workup.

PMID- 29068916
TI  - VISUAL ACUITY IN PATIENTS WITH STARGARDT DISEASE AFTER AGE 40.
AB  - PURPOSE: To better define visual acuity loss in patients with Stargardt disease
      later in life. METHODS: The most recent best-corrected visual acuities in the
      better-seeing eye of 221 patients with Stargardt disease over 40 years of age
      were recorded. Also included were the age at subjective onset for symptoms and
      duration of symptoms. Juvenile onset was defined as onset before age 21; adult
      onset was defined as onset between 21 and 40 years; and late onset was defined as
      onset at age 41 or later. RESULTS: The median age of the patients with Stargardt
      disease was 53.1 years. Twenty-four patients (10.9%) had worse than 20/400 best
      corrected visual acuity, and none had either light perception or no light
      perception vision. Whereas 17 of the 52 juvenile onset patients had best
      corrected visual acuity worse than 20/400, only 4 of 80 adult-onset patients and
      1 of 70 late-onset patients reached this level of acuity loss. CONCLUSION:
      Although many patients with Stargardt disease lose visual acuity to the 20/200 to
      20/400 range, and some lose visual acuity beyond 20/400, none of these patients
      reached either light perception or no light perception. The numbers found in this
      study will be valuable in counseling patients with Stargardt disease and could
      have value in planning treatment trials.

PMID- 29068917
TI  - TO PEEL OR NOT TO PEEL THE INTERNAL LIMITING MEMBRANE IN IDIOPATHIC EPIRETINAL
      MEMBRANES.
AB  - BACKGROUND: Epiretinal membranes (ERMs) have been described for more than 150
      years. Currently, they are a common indication for vitreoretinal surgery.
      Recently, there has been an increasing trend to peel the internal limiting
      membrane (ILM). Although ILM peeling has generally been accepted as a fundamental
      step in macular hole repair, its current role in ERM remains controversial.
      METHODS: Literature review. RESULTS: Proponents of ILM peeling argue that peeling
      of the ILM reduces the recurrence rate and facilitates a greater resolution of
      retinal folds. Opponents of ILM peeling show that the visual outcomes between
      eyes that undergo ILM peeling and those that do not have their ILM peeled are the
      same. Stripping of the ILM removes the Muller cell footplates, so it is
      reasonable to expect some Muller cell dysfunction. Adverse events such as
      eccentric paracentral macular holes, macular microscotomata, and retinal dimpling
      have been associated with ILM peeling. CONCLUSION: Internal limiting membrane
      peeling does not improve the functional outcomes after ERM surgery. Internal
      limiting membrane peeling reduces ERM recurrences, but many recurrences are not
      clinically significant. It remains unclear what the long-term effects of ILM
      peeling are. We should err on the side of caution and avoid routine ILM peeling
      in primary idiopathic ERM cases and should reserve it for recurrent and high risk
      of recurrence cases.

PMID- 29068918
TI  - Direct-to-Implant versus Two-Stage Tissue Expander/Implant Reconstruction: 2-Year
      Risks and Patient-Reported Outcomes from a Prospective, Multicenter Study.
AB  - BACKGROUND: Direct-to-implant breast reconstruction offers time-saving advantages
      over two-stage techniques. However, use of direct-to-implant reconstruction
      remains limited, in part, because of concerns over complication rates., The
      authors' aim was to compare 2-year complications and patient-reported outcomes
      for direct-to-implant versus tissue expander/implant reconstruction. METHODS:
      Patients undergoing immediate direct-to-implant or tissue expander/implant
      reconstruction were enrolled in the Mastectomy Reconstruction Outcomes
      Consortium, an 11-center prospective cohort study. Complications and patient
      reported outcomes (using the BREAST-Q questionnaire) were evaluated. Outcomes
      were compared using mixed-effects regression models, adjusting for demographic
      and clinical characteristics. RESULTS: Of 1427 patients, 99 underwent direct-to
      implant reconstruction and 1328 underwent tissue expander/implant reconstruction.
      Two years after reconstruction and controlling for covariates, direct-to-implant
      and tissue expander/implant reconstruction patients did not show statistically
      significant differences in any complications, including infection. Multivariable
      analyses found no significant differences between the two groups in patient
      reported outcomes, with the exception of sexual well-being, where direct-to
      implant patients fared better than the tissue expander/implant cohort (p =
      0.047). CONCLUSIONS: This prospective, multi-institutional study showed no
      statistically significant differences between direct-to-implant and tissue
      expander/implant reconstruction, in either complication rates or most patient
      reported outcomes at 2 years postoperatively. Direct-to-implant reconstruction
      appears to be a viable alternative to expander/implant reconstruction. This
      analysis provides new evidence on which to base reconstructive decisions.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 29068919
TI  - Do Bacteria and Biofilm Play a Role in Double-Capsule Formation around
      Macrotextured Implants?
AB  - BACKGROUND: The double capsule is a complication mostly described in aggressive
      macrotextured implants. Mechanical shear stress applied onto an immature
      periprosthetic capsule has been linked to their formation. The authors aim to
      demonstrate the role of bacterial phenotype and biofilm in the development of the
      double capsule. METHODS: Seven double capsules formed at the interface of
      macrotextured breast expander implants were studied using scanning electron
      microscopy. Two samples for each surface of the inner capsule layer (the
      prosthesis interface and the intercapsular space) were analyzed for bacteria cell
      size, bacterial density, and biofilm deposition. RESULTS: Although all routine
      bacterial cultures were negative, the prosthesis interface had both higher
      bacteria load and biofilm deposition compared with the intercapsular space (Mann
      Whitney U test, p = 0.004 and p = 0.008, respectively). Moreover, bacteria cell
      sizes were significantly smaller at the prosthesis interface in six of seven
      samples. Comparison of bacteria density and biofilm dispersion showed an increase
      of biofilm extracellular matrix deposition over 2000 cells/mm (linear regression,
      p = 0.0025). These results indicate a common trend among bacteria species.
      CONCLUSIONS: Bacterial expression between the different surfaces of the double
      capsule displays significant differences; bacteria at the prosthesis interface
      are mostly in a biofilm state, whereas they demonstrate a planktonic phenotype at
      the intercapsular space. When a sufficient amount of bacteria are present at a
      specific location, quorum sensing may trigger a biofilm phenotypic switch in
      planktonic bacteria cells. Biofilm formation may alter capsule formation through
      immune response, thereby weakening capsule strength and facilitating
      extracellular matrix delamination and double-capsule formation. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29068920
TI  - Five Steps to Internal Mammary Vessel Preparation in Less than 15 Minutes.
AB  - BACKGROUND: Modern breast reconstruction often involves microvascular
      reconstruction. The most common recipient vessels are the internal mammary artery
      and vein. Recently, there has been great focus on efficiency, but much of this
      emphasis has been directed to faster flap harvest or recovery protocols for
      expeditious discharge. An equally important aspect is internal mammary vessel
      preparation. METHODS: Breast reconstruction was performed in 415 patients (715
      breasts) using autologous tissue (850 flaps) from 2012 to 2016. In 97.6 percent
      of these breast reconstructions, the internal mammary vessels were used. The
      preparation of these vessels was routinely performed using the five-step
      technique described here. RESULTS: Internal mammary preparation time ranged from
      7 to 45 minutes (median, 15 minutes). The procedure involves five simplified
      steps, as follows: step 1, the rib is exposed by splitting the pectoralis major
      muscle; step 2, the perichondrium anterior to the cartilage is incised and
      dissected away from the cartilage; step 3, the cartilage is removed with a
      rongeur; step 4, laterally the perichondrium is elevated and incised (under
      direct vision, this perichondrium is then split directly over the vessels and the
      cranial and caudal flaps are resected); and step 5, careful dissection is
      performed on the artery and vein. CONCLUSIONS: Safe preparation of recipient
      vessels in microvascular reconstruction is essential for success. In modern
      breast reconstruction, the internal mammary artery and vein are typically used.
      Exposure of these vessels should be predictable and efficient. The authors have
      found that a systematic approach using the above five steps accomplishes these
      goals.

PMID- 29068921
TI  - Evidence-Based Clinical Practice Guideline: Autologous Breast Reconstruction with
      DIEP or Pedicled TRAM Abdominal Flaps.
AB  - The American Society of Plastic Surgeons commissioned a multistakeholder Work
      Group to develop recommendations for autologous breast reconstruction with
      abdominal flaps. A systematic literature review was performed and a stringent
      appraisal process was used to rate the quality of relevant scientific research.
      The Work Group assigned to draft this guideline was unable to find evidence of
      superiority of one technique over the other (deep inferior epigastric perforator
      versus pedicled transverse rectus abdominis musculocutaneous flap) in autologous
      tissue reconstruction of the breast after mastectomy. Presently, based on the
      evidence reported here, the Work Group recommends that surgeons contemplating
      breast reconstruction on their next patient consider the following: the patient's
      preferences and risk factors, the setting in which the surgeon works (academic
      versus community practice), resources available, the evidence shown in this
      guideline, and, equally important, the surgeon's technical expertise. Although
      theoretical superiority of one technique may exist, this remains to be reported
      in the literature, and future methodologically robust studies are needed.

PMID- 29068922
TI  - Breast Cleavage Remodeling with Fat Grafting: A Safe Way to Optimize Symmetry and
      to Reduce Intermammary Distance.
AB  - BACKGROUND: In their descriptions of the ideal breast, most studies have focused
      primarily on the dimensions, shape, and proportions. The distance between the
      breasts has only very rarely been considered. The intermammary distance and the
      medial symmetry between the breasts are important parts of the outcome of surgery
      and have a strong bearing on patient satisfaction. However, the control surgeons
      have over these factors is only relative, and depends heavily on the underlying
      anatomical characteristics of the patients. METHODS: Eighty-six patients
      undergoing breast augmentation, breast reduction, or mastopexy and breast
      reconstruction with separated or asymmetric breasts underwent fat grafting in the
      medial quadrants. Intermammary distances were measured before fat grafting and 12
      months later. Complications were also recorded. RESULTS: This technique obtained
      a statistically significant reduction in the mean intermammary distance (p <
      0.0001) from 3 +/- 0.6 cm (range, 1.6 to 5 cm) to 1.7 +/- 0.4 cm (range, 1 to 2.8
      cm) at 12-month follow-up. There were no major complications: one capsular
      contracture in a breast reconstruction requiring capsulotomy and an oil cyst
      requiring aspiration were reported. CONCLUSION: The authors' technique allows
      safe remodeling of the medial cleavage of the breast, reducing the intermammary
      distance and optimizing the symmetry between the breasts. CLINICAL QUESTION/LEVEL
      OF EVIDENCE: Therapeutic, IV.

PMID- 29068923
TI  - Impact of Patient Subtype and Surgical Variables on Abdominoplasty Outcomes: A 12
      Year Massachusetts General Hospital Experience.
AB  - BACKGROUND: The traditional abdominoplasty is one of the most common surgical
      procedures performed. This study evaluates the impact of different surgical
      techniques and clinical patient factors on abdominoplasty outcomes. METHODS: A
      retrospective review of consecutive patients undergoing abdominoplasty was
      performed. RESULTS: Seven hundred seventy-nine patients with a mean age of 43.7
      years and a body mass index of 27 kg/m underwent abdominoplasty. The majority
      were women (92.9 percent), and massive weight loss was present in 34.8 percent.
      Abdominoplasty techniques included traditional (59.4 percent), belt lipectomy
      (17.9 percent), fleur-de-lis (16.4 percent), umbilical float (9.2 percent), and
      mini-abdominoplasty (2.8 percent). Half of the study population [n = 384 (49.3
      percent)] had concurrent surgical procedures. Total complications (23.0 percent)
      consisted primarily of wound- and scar-related complications (15.3 percent).
      Approximately 60 percent of patients received heparin chemoprophylaxis, with
      overall thromboembolic and hematoma rates less than 1 percent. Univariate
      analysis revealed that massive weight loss (p = 0.04), fleur-de-lis (p = 0.03) or
      belt lipectomy (p = 0.05) techniques, and concurrent medial thigh lift (p <
      0.001) all significantly increased complications. Previous scars, amount of
      weight loss, operative time, liposuction, and other concurrent procedures did not
      affect total complications. Male sex (OR, 1.96; p = 0.04), fleur-de-lis technique
      (OR, 1.71; p = 0.04), and medial thigh lift (OR, 3.3; p < 0.001) were independent
      risk factors for total postoperative complications. CONCLUSION: This study
      demonstrates that abdominoplasty alone or in combination with liposuction and
      aesthetic breast surgery can be performed safely, with an acceptable complication
      profile. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 29068924
TI  - Injection of Compressed Diced Cartilage in the Correction of Secondary and
      Primary Rhinoplasty: A New Technique with 12 Years' Experience.
AB  - BACKGROUND: There are instances where small or large pockets are filled with
      diced cartilage in the nose, without use of wrapping materials. For this purpose,
      1-cc commercial syringes were used. The obtained results were partial and
      incomplete. For better and improved results, the author designed new syringes,
      with two different sizes, which compress the diced cartilage for injection.
      METHODS: The author presents his experience accrued over the past 12 years with
      2366 primary, 749 secondary, 67 cleft lip and nose, and a total of 3182
      rhinoplasties, using his new syringe design, which compresses diced cartilage and
      injects the diced cartilages as a conglutinate mass, simulating carved costal
      cartilage, but a malleable one. RESULTS: In 3125 patients, the take of cartilage
      graft was complete (98.2 percent) and a smooth surface was obtained, giving them
      a natural appearance. In 21 patients (0.65 percent), there was partial resorption
      of cartilage. Correction was performed with touch-up surgery by reinjection of a
      small amount of diced cartilage. In 36 patients (1.13 percent), there was
      overcorrection that, 1 year later, was treated by simple rasping. CONCLUSIONS:
      Compared with diced cartilage wrapped with Surgicel or fascia, the amount of
      injected cartilage graft is predictable because it consists purely of cartilage.
      The injected diced cartilage, because it is compressed and becomes a
      conglutinated mass, resembles a wood chip and simulates carved cartilage. It is
      superior to carved cartilage in that it is moldable, time saving, and gives a
      good result with no late show or warping. The injection takes only a few minutes.

PMID- 29068925
TI  - Managing Alar Flare in Rhinoplasty.
AB  - : Alar flare is a common feature that contributes to the width of the lower third
      of the nose. In the right patient, alar flare reduction can improve nasal harmony
      and facial aesthetic balance; however, it is also difficult to correct if
      conducted inappropriately or overzealously. The unique anatomy and diverse
      morphologies of the alar lobule, and the dynamic relationship between flare and
      changes in tip projection, must be considered. The authors provide guidelines for
      flare reduction: when it is appropriate and how to tailor the excision pattern to
      safely and effectively refine nasal width. Alar flare is classified into three
      types according to alar rim shape on basal view analysis. By designing the
      excision pattern based on specific flare type, the lower third of the nose is
      narrowed without creating an operated appearance. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, V.

PMID- 29068926
TI  - The Evolution of Chemical Peeling and Modern-Day Applications.
AB  - Despite the growth of technically more sophisticated skin resurfacing modalities,
      such as those based on light, radiofrequency, and ultrasound, chemical peel
      procedures have risen 5 to 25 percent over the past year alone. Chemexfoliation
      carries historical significance and has markedly evolved since its inception in
      ancient times. As a result of plastic surgery and dermatologic advancements,
      modern-day chemexfoliation offers plastic surgeons additional safe and effective
      options for patients with rhytides, dyschromias, and other signs of light- and
      environment-induced skin damage. This review discusses the historical evolution
      of chemexfoliation procedures, highlights modern-day practice habits, and touches
      on the clinically relevant applications of chemical peels.

PMID- 29068927
TI  - Orthognathic Surgery and Rhinoplasty to Address Nasomaxillary Hypoplasia.
AB  - : The treatment of nasomaxillary hypoplasia is challenging. The phenotype of
      Binder "syndrome" includes the following: midfacial hypoplasia, class III
      malocclusion, small or absent anterior nasal spine, flattened nose, horizontal
      nostrils, short columella, acute nasolabial angle, and a flat frontonasal angle.
      A staged approach is used, with orthognathic surgery to achieve vertical
      maxillary length and sagittal advancement, followed by rhinoplasty aimed to
      increase nasal tip projection, rotation, and columellar length. This article
      details the diagnosis and treatment of nasomaxillary hypoplasia, demonstrating
      the senior author's (D.M.S.) preferred approach and technical steps. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29068928
TI  - The Effect of Processing Technique on Fat Graft Survival.
AB  - BACKGROUND: Wide variations in fat graft survival have been reported. The authors
      hypothesize that treating the adipose tissue on Telfa gauze creates a processed
      lipoaspirate with a more functional adipokine profile that improves fat graft
      survival. METHODS: Suction-assisted lipoaspirate was harvested from humans and
      was either processed by centrifugation, rolled on Telfa gauze, or left
      unprocessed. Progenitor cell populations were quantified and characterized by
      flow cytometry. Glycerol-3-phosphate dehydrogenase assay was used to measure the
      functional adipocytes. The lipoaspirates were grafted into (n = 45) wild-type
      mice and harvested to assess fat graft persistence. Vascular endothelial growth
      factor and platelet-derived growth factor-BB secretions were measured by enzyme
      linked immunosorbent assay technique. RESULTS: Centrifuged lipoaspirate had a
      greater number of progenitor cells per gram of tissue than Telfa-processed and
      unprocessed lipoaspirate. However, Telfa-processed lipoaspirate had a greater
      number of functional adipocytes (0.104 U/ml) than centrifuged (0.080 U/ml) and
      unprocessed lipoaspirate (0.083 U/ml) on glycerol-3-phosphate dehydrogenase assay
      (p < 0.05). After 10 weeks of grafting, it had greater fat graft persistence
      (70.9 +/- 6.2 percent) than centrifuged (56.7 +/- 5.5 percent) and unprocessed
      lipoaspirate (42.2 +/- 2.7 percent) (p < 0.05). It also maintained a greater
      secretion of vascular endothelial growth factor and platelet-derived growth
      factor-BB at weeks 1 and 2 than centrifuged and unprocessed lipoaspirate.
      Furthermore, CD31 staining demonstrated an increase in vascular density of the
      Telfa-processed lipoaspirate at week 2 compared with the centrifuged lipoaspirate
      (37 +/- 1 percent and 14 +/- 4 percent per high-power field; p < 0.05).
      CONCLUSIONS: Lipoaspirate processing technique has a significant impact on fat
      graft survival rate. Increasing the number of functional adipocytes by processing
      the fat on Telfa gauze may augment the secretion of angiogenic and mitogenic
      adipokines within the graft, thereby improving its survivability. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29068929
TI  - Effect of Compound 21, a Selective Angiotensin II Type 2 Receptor Agonist, in a
      Murine Xenograft Model of Dupuytren Disease.
AB  - BACKGROUND: Although surgical excision and intralesional collagenase injection
      are mainstays in Dupuytren disease treatment, no effective medical therapy exists
      for recurrent disease. Compound 21, a selective agonist of the angiotensin II
      type 2 receptor, has been shown to protect against fibrosis in models of
      myocardial infarction and stroke. The authors investigated the potential use of
      compound 21 in the treatment of Dupuytren disease. METHODS: Human dermal
      fibroblasts were treated in vitro with compound 21 and assessed for viability
      using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,
      migration by means of scratch assay, and profibrotic gene transcription by means
      of quantitative reverse transcription polymerase chain reaction. Compound 21
      effects in vivo were assessed using a xenograft model. Dupuytren disease cord
      specimens from patients undergoing open partial fasciectomy were divided into two
      segments. Segments were implanted under the dorsal skin of nude mouse pairs.
      Beginning on day 5, one mouse from each pair received daily intraperitoneal
      injections of compound 21 (10 MUg/kg/day), and the other received vehicle. On day
      10, segments were explanted and submitted for immunohistochemistry. RESULTS:
      Human dermal fibroblasts treated with compound 21 displayed decreased migration
      and decreased gene expression of connective tissue growth factor, fibroblast
      specific protein-1, transforming growth factor-beta1, Smad3, and Smad4. Dupuytren
      disease segments from compound 21-treated mice demonstrated significantly reduced
      alpha-smooth muscle actin and Ki67 staining, with increased density of CD31
      staining vessels. CONCLUSIONS: Compound 21 significantly decreases expression of
      profibrotic genes and decreases myofibroblast proliferation as indicated by
      reduced Ki67 and alpha-smooth muscle actin expression. These findings support
      compound 21 as a potential novel treatment modality for Dupuytren disease.

PMID- 29068930
TI  - Lymphatic Territories (Lymphosomes) in the Rat: An Anatomical Study for Future
      Lymphatic Research.
AB  - BACKGROUND: Understanding the precise anatomy in experimental animals is crucial
      for correct design of research projects. Rats are commonly used for scientific
      research in plastic surgery because of their availability in academic
      institutions, moderate cost, and sizable vessels for microsurgical procedures. In
      past publications about rat anatomy, lymphatic mapping has been limited and
      incomplete. The aim of this study was to comprehensively map the superficial
      lymphatic system in the rat. METHODS: Twenty-seven Sprague-Dawley rats were used
      for this study. Indocyanine green fluorescence lymphography was used to identify
      the lymphatic vessels and lymph nodes. Under general anaesthesia, indocyanine
      green was injected intradermally at multiple spots along the dorsal and medial
      midlines, front and hind paws, ears, and tail. The course of the lymphatic
      vessels was traced on the skin with a marker pen and photographed. The
      superficial lymphatic vessels in each rat were sketched on a graphic template and
      all of the templates were superimposed using graphics software to define the
      relationship between the lymphatic vessel and sentinel node. RESULTS: Indocyanine
      green fluorescence lymphography was able to demonstrate the superficial lymphatic
      vessels in the rat. Six groups of regional lymph node/s were identified and
      lymphatic pathways to those nodes delineated. The authors' lymphosome concept was
      successfully applied to the rat, with six lymphosomes identified. CONCLUSIONS:
      The authors succeeded in performing superficial lymphatic mapping in the rat. The
      authors' anatomical findings can provide further information about the lymphatic
      system in the normal state and promote understanding of pathologic changes
      generated by surgical manipulation for future studies.

PMID- 29068931
TI  - Nerve Transfer versus Interpositional Nerve Graft Reconstruction for
      Posttraumatic, Isolated Axillary Nerve Injuries: A Systematic Review.
AB  - BACKGROUND: The purpose of this study was to compare functional outcomes between
      nerve grafting and nerve transfer procedures in the setting of isolated,
      posttraumatic axillary nerve injuries. METHODS: A systematic review was performed
      using the PubMed, Scopus, and Cochrane databases to identify all cases of
      isolated, posttraumatic axillary nerve injuries in patients aged 18 years or
      older. Patients who underwent axillary nerve reconstruction were included and
      categorized by technique: graft or transfer. Demographics were recorded,
      including age, time to operation, and presence of concomitant injuries.
      Functional outcomes were evaluated, including British Medical Research Council
      strength and range of motion for shoulder abduction. RESULTS: Ten retrospective
      studies met criteria, for a total of 66 patients (20 nerve grafts and 46 nerve
      transfers). Median time from injury to operation was equivalent across the nerve
      graft and nerve transfer groups (8.0 months versus 7.0 months; p = 0.41).
      Postoperative follow-up was 24.0 months for nerve grafting versus 18.5 months for
      nerve transfer (p = 0.13). Clinically useful shoulder abduction, defined as
      British Medical Research Council grade M3 or greater, was obtained in 100 percent
      of nerve graft patients versus 87 percent of nerve transfer patients (p = 0.09).
      Grade M4 or better strength was obtained in 85 percent of nerve graft patients
      and 73.9 percent of nerve transfer patients (p = 0.32). CONCLUSIONS: Significant
      differences in functional outcomes between nerve graft and transfer procedures
      for posttraumatic axillary nerve injuries are not apparent at this time.
      Prospective outcomes studies are needed to better elucidate whether functional
      differences do exist. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29068933
TI  - Discussion: A Systematic Review of Outcomes after Arthroscopic Debridement for
      Triangular Fibrocartilage Complex Tear.

PMID- 29068932
TI  - A Systematic Review of Outcomes after Arthroscopic Debridement for Triangular
      Fibrocartilage Complex Tear.
AB  - BACKGROUND: Evidence regarding the effectiveness of arthroscopic debridement for
      a triangular fibrocartilage complex tear is uncertain. The purpose of this study
      was to conduct a systematic review of outcomes to evaluate the effectiveness of
      debridement for triangular fibrocartilage complex tears. METHODS: The authors
      searched all available literature in the PubMed, Embase, and MEDLINE (Ovid)
      databases for articles reporting on triangular fibrocartilage complex tear
      debridement. Data collection included arc of motion, grip strength, patient
      reported outcomes, and complications. RESULTS: A total of 1723 unique studies
      were identified, of which 18 studies met the authors' criteria. The mean before
      and after arc of wrist extension/flexion motion values were 120 and 146 degrees
      (six studies). The mean before and after grip strength values were 65 percent and
      91 percent of the contralateral side (10 studies). Disabilities of the Arm,
      Shoulder, and Hand scores (six studies) and pain visual analogue scale scores
      (seven studies) improved from 39 to 18, and from 7 to 3, respectively. The mean
      pain visual analogue scale score after debridement was 1.9 in the ulnar-positive
      group and 2.4 in the ulnar-neutral and ulnar-negative groups. Eighty-seven
      percent of patients returned to their original work. CONCLUSIONS: Patients
      reported reduced pain and improved functional and patient-reported outcomes after
      debridement of triangular fibrocartilage complex tears. Most patients after
      debridement returned to previous work, with few complications. Although some of
      these cases may require secondary procedures, simple debridement can be performed
      with suitable satisfactory outcomes for cases with any type of ulnar variance.

PMID- 29068934
TI  - Resurfacing Capitate Pyrocarbon Implant versus Proximal Row Carpectomy Alone: A
      Comparative Study to Evaluate the Role of Capitate Prosthetic Resurfacing in
      Advanced Carpal Collapse.
AB  - BACKGROUND: The Resurfacing Capitate Pyrocarbon Implant associated with proximal
      row carpectomy has been used to treat symptomatic advanced carpal collapse,
      widening the indications of proximal row carpectomy to patients with capitate
      head arthritis. The authors retrospectively compared their case series of implant
      versus carpectomy alone, analyzing whether prosthetic implant outcomes could be
      similar to those of proximal row carpectomy even with a higher stage of
      osteoarthritis. METHODS: Fifty-seven patients who underwent surgery for wrist
      osteoarthritis (minimum follow-up, 2 years) were selected retrospectively. Twenty
      five patients (scapholunate advanced collapse/scaphoid nonunion advanced collapse
      stage III to IV and Kienbock disease stage IV) underwent proximal row carpectomy
      plus Resurfacing Capitate Pyrocarbon Implant (group A); 32 patients (scapholunate
      advanced collapse/scaphoid nonunion advanced collapse stage I to II and Kienbock
      disease stage III) underwent carpectomy alone (group B). Mean follow-up was 33
      months. Patients were evaluated clinically and radiographically. Patient-Rated
      Wrist Evaluation and Disabilities of the Arm, Shoulder, and Hand questionnaire
      scores were assessed. RESULTS: Group A showed consistent pain relief (visual
      analogue scale score of 2), while preserving wrist mobility (flexion, 27 degrees;
      extension, 33 degrees) and grip strength (54 percent compared with the
      contralateral side). Average Disabilities of the Arm, Shoulder, and Hand
      questionnaire score was 20, and average Patient-Rated Wrist Evaluation score was
      28. No statistically significant difference was observed between groups for all
      outcomes, except for better extension (p < 0.05) in group B. CONCLUSIONS: Even
      starting from a higher grade of osteoarthritis, Resurfacing Capitate Pyrocarbon
      Implant plus proximal row carpectomy showed satisfying results, compared with
      those obtained with just carpectomy. Data show that indications for proximal row
      carpectomy can be widened by using the implant, without worsening outcomes. The
      implant could be a useful alternative to more aggressive salvage procedures in
      case of capitate head and lunate fossa osteoarthritis involvement. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29068935
TI  - Orthognathic Surgery Has a Significant Effect on Perceived Personality Traits and
      Emotional Expressions.
AB  - BACKGROUND: The effects of orthognathic surgery go beyond objective cephalometric
      correction of facial and dental disproportion and malocclusion, respectively. The
      authors hypothesized that there is tangible improvement following surgery that
      alters publicly perceived personality traits and emotions. METHODS: The authors
      used Amazon.com's Mechanical Turk (MTurk), a crowdsourcing tool, to determine how
      preoperative and postoperative images of orthognathic surgery patients were
      perceived on six personality traits and six emotional expressions based on
      posteroanterior and lateral photographs. Blinded respondents provided demographic
      information and were randomly assigned to one of two sets of 20 photographs (10
      subjects before and after surgery). RESULTS: Data on 20 orthognathic surgery
      patients were collected from 476 individuals. The majority of participants were
      female (52.6 percent), 18 to 39 years old (67.9 percent), Caucasian (76.6
      percent), had some college or technical training or graduated college (72.7
      percent), and had an annual income between $20,000 and $99,999 (74.6 percent). A
      paired t test analysis found that subjects were perceived significantly more
      favorably after orthognathic surgery in 12 countenance categories: more dominant,
      trustworthy, friendly, intelligent, attractive, and happy; and also less
      threatening, angry, surprised, sad, afraid, and disgusted (p < 0.05). Raters with
      the highest annual income perceived a greater magnitude of dominance after
      surgery than those earning less (p < 0.001). CONCLUSIONS: There is significant
      improvement in the countenance of patients after orthognathic surgery, with both
      perceived personality traits and emotions deemed more favorable. Additional work
      is needed to better understand the physiologic underpinnings of such findings.
      Crowdsourcing technology offers a unique opportunity for surgeons to gather data
      regarding laypeople's perceptions of surgical outcomes in areas such as
      orthognathic surgery.

PMID- 29068936
TI  - Craniosynostosis Surgery: Does Hospital Case Volume Impact Outcomes or Cost?
AB  - BACKGROUND: The relationships between hospital/surgeon characteristics and
      operative outcomes and cost are being scrutinized increasingly. In patients with
      craniosynostosis specifically, the relationship between hospital volume and
      outcomes has yet to be characterized. METHODS: Subjects undergoing
      craniosynostosis surgery between 2004 and 2015 were identified in the Pediatric
      Health Information System. Outcomes were compared between two exposure groups,
      those undergoing treatment at a high-volume institution (>40 cases per year), and
      those undergoing treatment at a low-volume institution (40 cases per year).
      Primary outcomes were any complication, prolonged length of stay, and increased
      total cost. RESULTS: Over 13,000 patients (n = 13,112) from 49 institutions met
      inclusion criteria. In multivariate regression analyses, subjects treated in high
      volume centers were less likely to experience any complication (OR, 0.764; p <
      0.001), were less likely to have an extended length of stay (OR, 0.624; p <
      0.001), and were less likely to have increased total cost (OR, 0.596; p < 0.001).
      Subjects undergoing strip craniectomy in high-volume centers were also less
      likely to have any complication (OR, 0.708; p = 0.018) or increased total cost
      (OR, 0.51; p < 0.001). Subjects undergoing midvault reconstruction in high-volume
      centers were less likely to experience any complications (OR, 0.696; p = 0.002),
      have an extended length of stay (OR, 0.542; p < 0.001), or have increased total
      cost (OR, 0.495; p < 0.001). CONCLUSION: In hospitals performing a high volume of
      craniosynostosis surgery, subjects had significantly decreased odds of
      experiencing a complication, prolonged length of stay, or increased total cost
      compared with those undergoing treatment in low-volume institutions. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29068937
TI  - Three-Dimensional Computer-Assisted Two-Layer Elastic Models of the Face.
AB  - To make three-dimensional computer-assisted elastic models for the face, we
      decided on five requirements: (1) an elastic texture like skin and subcutaneous
      tissue; (2) the ability to take pen marking for incisions; (3) the ability to be
      cut with a surgical knife; (4) the ability to keep stitches in place for a long
      time; and (5) a layered structure. After testing many elastic solvents, we have
      made realistic three-dimensional computer-assisted two-layer elastic models of
      the face and cleft lip from the computed tomographic and magnetic resonance
      imaging stereolithographic data. The surface layer is made of polyurethane and
      the inner layer is silicone. Using this elastic model, we taught residents and
      young doctors how to make several typical local flaps and to perform
      cheiloplasty. They could experience realistic simulated surgery and understand
      three-dimensional movement of the flaps.

PMID- 29068938
TI  - Pediatric Obstructive Sleep Apnea: Consensus, Controversy, and Craniofacial
      Considerations.
AB  - Pediatric obstructive sleep apnea, characterized by partial or complete
      obstruction of the upper airway during sleep, is associated with multiple adverse
      neurodevelopmental and cardiometabolic consequences. It is common in healthy
      children and occurs with a higher incidence among infants and children with
      craniofacial anomalies. Although soft-tissue hypertrophy is the most common
      cause, interplay between soft tissue and bone structure in children with
      craniofacial differences may also contribute to upper airway obstruction. Snoring
      and work of breathing are poor predictors of obstructive sleep apnea, and the
      gold standard for diagnosis is overnight polysomnography. Most healthy children
      respond favorably to adenotonsillectomy as first-line treatment, but 20 percent
      of children have obstructive sleep apnea refractory to adenotonsillectomy and may
      benefit from positive airway pressure, medical therapy, orthodontics,
      craniofacial surgery, or combined interventions. For children with impairment of
      facial skeletal growth or craniofacial anomalies, rapid maxillary expansion,
      midface distraction, and mandibular distraction have all been demonstrated to
      have therapeutic value and may significantly improve a child's respiratory
      status. This Special Topic article reviews current theories regarding the
      underlying pathophysiology of pediatric sleep apnea, summarizes standards for
      diagnosis and management, and discusses treatments in need of further
      investigation, including orthodontic and craniofacial interventions. To provide
      an overview of the spectrum of disease and treatment options available, a
      deliberately broad approach is taken that incorporates data for both healthy
      children and children with craniofacial anomalies.

PMID- 29068939
TI  - Watch Out for Wild Animals: A Systematic Review of Upper Extremity Injuries
      Caused by Uncommon Species.
AB  - BACKGROUND: Across the world, many species of nondomesticated animals dwell among
      humans in metropolitan areas. Rare animal bites pose a dilemma for hand surgeons,
      as they often result in operative injuries and recalcitrant infections. The
      authors treated an 85-year-old man who experienced severe cellulitis of the index
      finger following an opossum bite. This case prompted a systematic review of upper
      extremity injuries caused by species other than dogs, cats, snakes, and insects.
      METHODS: The authors conducted a systematic review of PubMed and Scopus databases
      to identify relevant articles published between 1980 and 2016. Two reviewers
      critically appraised the studies that met inclusion and exclusion criteria.
      RESULTS: The hand infection in the man who sustained an opossum bite at the
      authors' institution was successfully treated with targeted antibiotic therapy,
      hand elevation, and splinting. Seventy-one articles met inclusion criteria for
      and were included in this systematic review. The vast majority of existing
      articles represent level IV and level V evidence. The relevant literature
      suggests that the majority of hand infections attributable to animal bites and
      stings are polymicrobial. CONCLUSIONS: Injuries secondary to aquatic animals
      appear to be the most frequently described in the literature, and hot water
      immersion should be used for the majority of envenomation attributable to aquatic
      species. Infections can often be treated with an aminopenicillin antibiotic
      combined with a beta-lactamase inhibitor. Given the variability in presentation
      and potential for sequelae such as soft-tissue necrosis and systemic reactions,
      hand surgeons should approach such upper extremity injuries with a high degree of
      caution.

PMID- 29068940
TI  - Not All Gustilo Type IIIB Fractures Are Created Equal: Arterial Injury Impacts
      Limb Salvage Outcomes.
AB  - BACKGROUND: Open tibia fractures are commonly stratified by the Gustilo
      classification, an orthopedic grading system that does not incorporate the
      presence of arterial injury when limb perfusion is intact. In the authors'
      experience, however, the presence of arterial injury appears to negatively impact
      microsurgical outcomes. METHODS: In a retrospective review of 806 lower extremity
      reconstructions between 1979 and 2016, 361 soft-tissue flaps performed for
      Gustilo type IIIB/C coverage met inclusion criteria. Patient demographics, flap
      characteristics, and outcomes were analyzed. RESULTS: Most patients suffered type
      IIIB [n = 332 (91.9 percent)] injuries; 29 (8.0 percent) had type IIIC injuries.
      Preoperative angiography [n = 243 (67.3 percent)] demonstrated arterial injury in
      126 (51.8 percent); 27 arterial injuries were identified intraoperatively; and
      the overall incidence was 153 of 361 (42.4 percent). Complications occurred in
      143 flaps (39.6 percent) and included 37 partial losses (10.2 percent) and 31
      total losses (8.6 percent). Injured recipient arteries [n = 62 (17.2 percent)]
      had more complications (p = 0.004); specifically, increased take-backs (p =
      0.009). Decreasing vessel runoff increased the risk of complications (p = 0.025),
      take-backs (p = 0.007), and total flap failures (p = 0.024) accordingly.
      Specifically, among grade IIIB injuries, controlling for age, sex, time since
      injury, and vein number, single-vessel runoff was associated with higher rates of
      complications (relative risk, 3.07; p = 0.012), take-backs (relative risk, 3.43;
      p = 0.013), and total flap failures (relative risk, 4.80; p = 0.010) compared
      with three-vessel runoff. CONCLUSIONS: Arterial injury was common among Gustilo
      type IIIB patients and correlated with increased reconstructive complications.
      Nonischemic arterial injury appears to negatively impact reconstructive outcomes
      and should be accounted for when considering free tissue transfer for lower
      extremity salvage. The authors propose a 3-2-1 modification of the Gustilo type
      IIIB classification to incorporate degree of arterial injury, as it appears to
      add prognostic value and certainly influences the reconstructive plan. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Risk, IV.

PMID- 29068941
TI  - Discussion: Not All Gustilo Type IIIB Fractures Are Created Equal: Arterial
      Injury Impacts Limb Salvage Outcomes.

PMID- 29068942
TI  - Eyelid Reconstruction.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Describe eyelid anatomy and demonstrate full understanding of the critical
      structures and basic principles of eyelid reconstruction. 2. Evaluate individual
      defects, analyze the missing components, and formulate a reconstructive
      algorithm. 3. Anticipate potential complications and design effective strategies
      to manage and treat common complications following eyelid reconstruction.
      SUMMARY: Defects of the eyelid can result from trauma, burns, or resection of
      cutaneous malignancies. Repair of eyelid defects presents unique challenges to
      reconstructive surgeons. A fundamental understanding of eyelid anatomy and
      familiarity with the myriad of options for reconstruction are critical for
      achieving optimal outcomes. Under ideal circumstances, the aims of reconstruction
      should be to restore form and function and to replace "like with like."

PMID- 29068943
TI  - Social Media and the Plastic Surgery Patient.
AB  - BACKGROUND: Many plastic surgeons use social media as a marketing tool to attract
      and retain patients, but information about how patients use social media and
      their preferred types of plastic surgery posts have been lacking. METHODS: To
      investigate patients' preferred social media networks and the type of posts they
      wished to see, a cross-sectional study was conducted in a single aesthetic
      practice of two plastic surgeons by surveying 100 consecutive patients. RESULTS:
      The age of the patients averaged 44.4 years (range, 17 to 78 years). Facebook had
      the greatest patient use and engagement, with YouTube second in use, and
      Instagram second in number of engaged users. Over half used Pinterest, but with
      little daily engagement. Only one-fourth used Snapchat, but the percentage of
      users who were highly engaged was second only to Facebook. The least popular
      network was Twitter, with the fewest patient users and least engagement. Social
      media played a minor role compared with the practice's Web site in both
      influencing patients to choose the practice and providing information on the day
      of the appointment. Patients most wanted to see posts on a plastic surgeon's
      social media platform related to practice information, before-and-after
      photographs, and contests. Articles about plastic surgery held the least
      interest. Among five types of Web site content, patients expressed most interest
      in before-and-after photographs. CONCLUSIONS: This study is the first to
      articulate the plastic surgery patient perspective regarding social media. The
      findings aim to help plastic surgeons maximize their influence on their target
      audience.

PMID- 29068944
TI  - Discussion: Social Media and the Plastic Surgery Patient.

PMID- 29068946
TI  - Mixed Reality with HoloLens: Where Virtual Reality Meets Augmented Reality in the
      Operating Room.
AB  - Virtual reality and augmented reality devices have recently been described in the
      surgical literature. The authors have previously explored various iterations of
      these devices, and although they show promise, it has become clear that virtual
      reality and/or augmented reality devices alone do not adequately meet the demands
      of surgeons. The solution may lie in a hybrid technology known as mixed reality,
      which merges many virtual reality and augmented realty features. Microsoft's
      HoloLens, the first commercially available mixed reality device, provides
      surgeons intraoperative hands-free access to complex data, the real environment,
      and bidirectional communication. This report describes the use of HoloLens in the
      operating room to improve decision-making and surgical workflow. The pace of
      mixed reality-related technological development will undoubtedly be rapid in the
      coming years, and plastic surgeons are ideally suited to both lead and benefit
      from this advance.

PMID- 29068947
TI  - Discussion: Mixed Reality with HoloLens: Where Virtual Reality Meets Augmented
      Reality in the Operating Room.

PMID- 29068945
TI  - Impact of an Event Reporting System on Resident Complication Reporting in Plastic
      Surgery Training: Addressing an ACGME and Plastic Surgery Milestone Project Core
      Competency.
AB  - BACKGROUND: The Accreditation Council for Graduate Medical Education and Plastic
      Surgery Milestone Project has identified practice-based learning and improvement,
      which involves systematically analyzing current practices and implementing
      changes, as a core competency in residency education. In surgical care,
      complication reporting is an essential component of practice-based learning and
      improvement as complications are analyzed in morbidity and mortality conference
      for quality improvement. Unfortunately, current methods for capturing a
      comprehensive profile of complications may significantly underestimate the true
      occurrence of complications. Therefore, the objectives of this study are to
      evaluate an intervention for complication reporting and compare this to current
      practice, in a plastic surgery training program. METHODS: This is a
      preintervention and postintervention study evaluating resident reporting of
      complications on a plastic surgery service. The intervention was an online event
      reporting system developed by department leadership and patient safety experts.
      The cohorts consisted of all patients undergoing surgery during two separate 3
      month blocks bridged by an implementation period. A trained reviewer recorded
      complications, and this served as the reference standard. Fisher's exact test was
      used for binary comparisons. RESULTS: There were 32 complications detected in 219
      patients from June to August of 2015 and 35 complications in 202 patients from
      October to December of 2015. The proportion of complications reported in the
      preintervention group was nine of 32 (28.1 percent). After the intervention, this
      significantly increased to 32 of 35 (91.4 percent) (p < 0.001). CONCLUSION: An
      intervention using an event reporting system, supported by departmental
      leadership, led to significant improvements in complication reporting by plastic
      surgery residents.

PMID- 29068948
TI  - Just Because You Can, Doesn't Mean You Should.

PMID- 29068949
TI  - Gender Affirmation: Medical & Surgical Perspectives.

PMID- 29068950
TI  - Time and Life Management for Medical Students and Residents.

PMID- 29068951
TI  - The Anterior Intercostal Artery Perforator Flap: Clinical Applications in Partial
      Breast Reconstruction.

PMID- 29068952
TI  - Reply: Late Surgical-Site Infection in Immediate Implant-Based Breast
      Reconstruction.

PMID- 29068953
TI  - Scientific Comparison and Validity Requires Appropriate Use.

PMID- 29068954
TI  - Reply: Comparison of Different Acellular Dermal Matrices in Breast
      Reconstruction: The 50/50 Study.

PMID- 29068955
TI  - Prospective Analysis of Satisfaction by Means of BREASTQ in 156 Patients Who
      Underwent Breast Reduction.

PMID- 29068956
TI  - Topographic Analysis of the Supratrochlear Artery and the Supraorbital Artery:
      Implication for Improving the Safety of Forehead Augmentation.

PMID- 29068957
TI  - Reply: Topographic Analysis of the Supratrochlear Artery and the Supraorbital
      Artery: Implication for Improving the Safety of Forehead Augmentation.

PMID- 29068958
TI  - Platysma Bands: Is a Change Needed in the Surgical Paradigm?

PMID- 29068959
TI  - Reply: Platysma Bands: Is a Change Needed in the Surgical Paradigm?

PMID- 29068960
TI  - Quality of Life after Face Transplantation: Outcomes, Assessment Tools, and
      Future Directions.

PMID- 29068961
TI  - Comparing Round and Anatomically Shaped Implants in Augmentation Mammaplasty: The
      Experts' Ability to Differentiate the Type of Implant.

PMID- 29068963
TI  - Optimizing Outcomes in Pharyngoesophageal Reconstruction and Neck Resurfacing: 10
      Year Experience of 294 Cases.

PMID- 29068962
TI  - Reply: Comparing Round and Anatomically Shaped Implants in Augmentation
      Mammaplasty: The Experts' Ability to Differentiate the Type of Implant.

PMID- 29068964
TI  - An Algorithm for Managing Intraosseous Vascular Anomalies of the Craniofacial
      Skeleton.
AB  - BACKGROUND: Intraosseous vascular anomalies (IOVA) are rare in the craniofacial
      skeleton and present a diagnostic and therapeutic challenge. This study aims to
      describe the clinical management based on a large case series. METHODS: A
      retrospective chart review was performed and 9 IOVA were identified over a 15
      year period. Data on demographics, diagnostic features, clinical management, and
      outcomes were reviewed. RESULTS: Five frontal bone IOVA and 4 orbital IOVA were
      identified. The postoperative follow-up ranged from 4 months to 4 years. All 9
      lesions were diagnosed with computed tomography (CT) imaging. Magnetic resonance
      imaging (MRI) was used to delineate soft tissue involvement in 2 patients
      presenting with oculo-orbital dystopia and ophthalmoplegia. En bloc excision was
      performed in all patients. Preoperative interventional embolization was critical
      in the successful resection of an orbital IOVA following 2 previously failed
      attempts that were aborted secondary to hemorrhage. Intraoperative 3-dimensional
      stereotactic navigation was used for the accurate en bloc excision of a frontal
      IOVA to prevent injury to the frontal sinus. Reconstruction of esthetic and
      functional deformities was successfully accomplished. CONCLUSION: The diagnosis
      of IOVA relies primarily on clinical assessment and CT imaging. Further
      interpretation of the involvement of periorbital, facial, and intracranial soft
      tissue is best defined by MRI. Multidisciplinary care with interventional
      radiology and neurosurgery must be considered for ensuring the safe and adequate
      en bloc excision of craniofacial IOVA.

PMID- 29068965
TI  - Single-Stage Repair of Palatal Fistula and Velopharyngeal Incompetence by the New
      L Flap.
AB  - OBJECTIVE: To describe and assess the results of use of the new L-shaped
      posterior pharyngeal flap for repair of both palatal fistula and velopharyngeal
      incompetence. METHODS: This study included 10 patients who were diagnosed to have
      soft palate fistula and persistent velopharyngeal insufficiency (VPI). L-shaped
      superiorly based pharyngeal flap was harvested from oropharynx and inserted into
      the soft palate closing the fistula after fistula trimming. The palatal part of
      the flap (transverse limb) was spread 1 cm horizontally and 1 cm in the
      anteroposterior direction in soft palate at fistula site closing it without
      tension. Prior to and after surgery, patients were assessed by examination, video
      nasoendoscopy, and speech assessment. RESULTS: Closure of the palatal fistula
      could be achieved in all patients. Postoperative speech assessment showed
      significant improvement in the nasal emission, resonance, intraoral pressure, and
      articulation defects. Grade 4 velopharyngeal valve closure (complete closure)
      could be achieved in all patients. No patients showed dehiscence (partial or
      total) of the flap and no obstructive sleep apnea reported. CONCLUSION: The new
      used L-shaped pharyngeal flap could properly close palatal fistula and correct
      velopharyngeal functions (closure and speech) in patients with persistent VPI
      with no reported significant complication and without the need for palatal
      dissection or flaps.

PMID- 29068966
TI  - Dermal Regenerative Template as a Cost-Effective Alternative for Complex Scalp
      Reconstruction.
AB  - BACKGROUND: Use of dermal regeneration template (DRT) is well documented in the
      literature for complex wounds ranging from the scalp, trunk, and lower extremity.
      METHODS: A retrospective cohort study was performed of the use of dermal
      regeneration template and skin grafting. A literature review was performed of all
      studies where DRT was used for scalp reconstruction. RESULTS: Patients in the DRT
      cohort had an average age of 70, with wounds averaging 108 cm in size. These
      patients also had a relatively low rate of complications (0.4), a short hospital
      stay (average 2 days), and a relatively short operating room time (114 minutes).
      CONCLUSION: This study demonstrates dermal regeneration template to be an
      effective and reliable option for soft tissue reconstruction with minimal
      morbidity and complications in patients with extensive medical comorbidities.
      Emerging applications include radiation exposure and hypercoaguable states.

PMID- 29068967
TI  - Surgical Hypercorrection of Trigonocephaly: Evaluation of Surgical Outcomes.
AB  - BACKGROUND: A lasting correction of trigonocephaly is difficult to achieve, as a
      durable correction requires significant expansion to overcome galeal restriction
      and soft tissue recoil of the scalp. High rates of relapse have been reported
      throughout the literature. The specific aim of this study was to determine if the
      senior author's method of "hypercorrection" decreases relapse and the need for
      subsequent revisional surgery. METHODS: Patients who underwent operative
      correction of metopic craniosynostosis between 1988 and 2011 were reviewed. All
      patients underwent the "hypercorrection" technique performed by the senior
      author. Hypercorrection consisted of a fronto-orbital advancement of 2.5 to 3.5
      cm and a concomitant hyperexpansion of bitemporal projection. Split cranial bone
      grafting ensured adequate coverage of the significantly expanded cranial vault.
      Only patients who had at least 5 years of follow-up were included for review of
      outcomes. Relapse was defined as recurrence of bitemporal constriction or lateral
      orbital retrusion, requiring surgical correction. RESULTS: Fifty-eight patients
      met criteria. Mean age at the time of surgery was 11 months. Mean follow-up was
      9.0 years. During this time, 2 patients exhibited relapse requiring camouflage
      procedures. Cranial bone defects were found in 4 patients (7%), 3 of whom
      underwent cranial bone grafting, while 1 underwent methylmethacrylate placement
      at an outside institution. One patient underwent fat grafting for areas of soft
      tissue irregularity. No patients exhibited persistent sequelae of hypercorrection
      significant enough to require repeat fronto-orbital advancement. CONCLUSION:
      Surgical hypercorrection of trigonocephaly seems to minimize relapse and the need
      for revision in long-term follow-up and is therefore an important technique to
      consider.

PMID- 29068968
TI  - Isolated Intraorbital Frontosphenoidal Synostosis.
AB  - Unilateral anterior plagiocephaly is most commonly the result of deformational
      plagiocephaly or unilateral coronal synostosis, a premature fusion of the
      frontoparietal suture. However, other sutures within the coronal ring have been
      implicated in producing anterior cranial asymmetries. These fusions can occur in
      isolation or in concert with adjacent sutures. The frontosphenoidal suture is one
      such suture within the coronal ring that has been involved both concomitantly
      with and independently of frontoparietal suture fusion. Although isolated
      frontosphenoidal synostosis has been presented previously in the literature,
      these reports include patients with fusion of the extraorbital portion of the
      frontosphenoidal suture. This clinical report presents the first clearly
      documented patient of isolated frontosphenoidal synostosis that occurs entirely
      within the intraorbital region.The patient presented to Plastic Surgery Clinic at
      3 months of age with left frontal flattening, supraorbital rim retrusion, and
      temporal bulging that was noted soon after birth. Computed tomography analysis
      revealed an isolated fusion of the greater and lesser wings of the sphenoid bone
      to the frontal bone on the left side. The patient had no family history of
      cranial anomalies and genetic testing was negative for mutations. The infant was
      treated with a cranial orthotic for 3 months, underwent open fronto-orbital
      advancement and cranial vault remodeling at 6 months, and continued wearing a
      cranial orthotic for another 4.5 months. Following surgical and orthotic
      treatment, the patient achieved a satisfactory result.

PMID- 29068969
TI  - Positive Effect of Incubated Adipose-Derived Mesenchymal Stem Cells on Microfat
      Graft Survival.
AB  - Autologous fat grafting is commonly used for soft tissue augmentation, but its
      unpredictably high resorption rate remains a major limitation. Although adipose
      derived mesenchymal stem cells (ASCs) are an attractive candidate for enhancing
      graft retention, their poor posttransplantation viability limits their
      application. The authors aimed to evaluate the effect of incubated ASCs on
      microfat graft survival in an immunocompromised mouse model. Lipoaspirates for
      microfat injection were collected from the wasted lower abdominal adipose tissues
      of 5 patients who had undergone breast reconstructive surgery with an abdominal
      flap. Adipose-derived mesenchymal stem cells were also isolated and proliferated
      from these fat tissues. Sixty athymic mice were randomly allocated to a control
      group (microfat grafting alone; n = 30) or ASCs group (microfat grafting plus
      simultaneous human ASCs injection; n = 30). The volume and weight of survived fat
      were measured at 8 and 16 weeks, and histopathological and immunologic staining
      was performed at 16 weeks. The survived fat volume of the ASCs group was
      significantly greater than that of the control group at 8 and 16 weeks, whereas
      the weight of survived fat tissues did not significantly differ. Histologic
      evaluation of the harvested fat indicated significantly higher levels of
      adipocytes, and fewer cysts and fibrosis in the tissues in the ASCs group than in
      the control group. The ASCs group also exhibited a significantly higher number of
      capillary vessels than the control group on CD31 and alpha-smooth muscle actin
      staining. In conclusion, transplanted fat survival is markedly higher when
      simultaneous microfat graft and ASCs injection were performed, as compared with
      that in the classical microfat graft alone method in mice; this improvement was
      primarily attributed to the increased ability to produce blood vessels.

PMID- 29068970
TI  - More Than Meets the Eye: The Effect of Intercanthal Distance on Perception of
      Beauty and Personality.
AB  - In judging normalcy, surgeons rely on established facial anthropometric measures
      and proportions. However, there exists a range of "normal," and a degree of
      disproportion may be considered more attractive. The authors set out to determine
      how changes in only intercanthal distance affect the layperson's perception of
      beauty and personality traits of a face. The authors used Amazon.com's Mechanical
      Turk (MTurk), a crowdsourcing tool, to determine how changes in intercanthal
      distance affect overall perception of beauty and personality. MTurk respondents
      provided demographic information and were asked to survey 16 female subjects,
      each digitally edited to be hypoteloric or hyperteloric. Data were collected from
      490 MTurk crowd raters. Paired t test analysis found that respondents perceived
      subjects to be more submissive, friendly, and attractive with increased
      intercanthal distance (P < 0.05). Women respondents were less likely to perceive
      change in regards to how unthreatening and how intelligent the subject appeared
      upon intercanthal widening (P < 0.05). Compared with Caucasian respondents,
      minorities (Asian- and African-American) were more likely to perceive difference
      in submissiveness, threat, intelligence, and attractiveness with increased
      intercanthal distance (P < 0.05). All respondents >46 years of age were less
      likely to perceive a change in any of the 7 traits upon intercanthal widening,
      compared with respondents between 18 and 25 years of age (P < 0.05). The
      layperson perceives significant increases in a female subject's submissivness,
      friendliness, and attractiveness with an intercanthal distance increase of 10%
      from normal. Surgeons should be aware of this when correcting hypertelorism,
      given the potential positive impact of a slightly increased intercanthal distance
      on perceived beauty and personality.

PMID- 29068971
TI  - Alterations in Nasal Sensibility Following Calcium Hydroxyapatite Dorsal
      Augmentation.
AB  - BACKGROUND: There are a many types of filler products that surgeons used for soft
      tissue augmentation. Soft Tissue Fillers, also known as injectable grafts, is a
      medical device implants. One of the materials used in soft tissue fillers is
      calcium hydroxylapatite (CaHA) that is commonly used for treating nasal
      deformities and nasal reshaping too. Calcium hydroxylapatite is a kind of mineral
      that can be found in human teeth and bones. It is considered long-lasting but
      nonpermanent filler and is biocompatible with human tissue. AIM: The aim of this
      study is to measure the alterations in sensibility and patient satisfaction
      following CaHA filler injection. PATIENT/METHODS: In a prospective study, 30
      patients who underwent CaHA filler injections from January to December 2016 at a
      Private Tertiary Care Hospital in Riyadh, Saudi Arabia were included. RESULTS:
      Means and standard deviations were measured for pressure threshold values at each
      test area preprocedure 2 weeks after procedure (). Alterations between pre and
      postprocedure values were verified using the match-paired Student t test
      preprocedures. None of the patients had any subjective sensory symptoms. Majority
      of patients were extremely satisfied with the results.(Table is included in full
      text article.) CONCLUSION:: With correct anatomic knowledge and precise technique
      in doing the CaHA gel injection procedure, nasal sensibility will not be altered.
      In addition, injection of CaHA gel can be valuable tool for plastic surgeons to
      consider for nasal reshaping.

PMID- 29068972
TI  - Surgical Management of Migraine Headache.
AB  - Migraine surgery has been recently reported as an alternative to medical
      management to provide long-term relief in migraine sufferers. A prospective study
      was designed wherein patients diagnosed with migraine were screened for surgery
      by injecting botulinum toxin type A at the primary trigger site. Surgery
      consisted of corrugator supercilii muscle resection to decompress supra-trochlear
      and supra-orbital nerves with avulsion of zygomaticotemporal branch of trigeminal
      nerve. Using pre and postsurgery questionnaires, information regarding the degree
      of reduction of migraines with regard to severity and frequency; and surgical
      site problems was acquired. Thirty patients volunteered for migraine surgery.
      Mean migraine headaches reduced from 15.2 +/- 6.3 episodes per month to 1.9 +/-
      2.4 episodes per month (P < 0.0001) postsurgery. The mean intensity of migraine
      headache also reduced from a preoperative 7.3 +/- 3.5 to a postoperative of 1.3
      +/- 1.4 (P < 0.0001). Fourteen (46.7%) patients reported complete elimination of
      migraine after surgery while an equal number reported significant relief of
      symptoms. Two (6.6%) patients failed to notice any significant improvement after
      surgery. The mean follow-up period was 11.1 +/- 2 months with no major surgical
      complications. Results of the authors' study confirm prior published results that
      surgical treatment of migraine is a reality. Surgeons can easily incorporate this
      simple surgical procedure in their armamentarium to offer relief to numerous
      migraine patients.

PMID- 29068973
TI  - Rigid External Distractor-Aided Advancement After Simultaneously Performed LeFort
      III Osteotomy and Fronto-Orbital Advancement.
AB  - Due to the complex development of the craniofacial skull, corrective surgery is a
      major challenge for patients with severe craniofaciostenosis. Although fronto
      orbital advancement and simultaneous LeFort-III osteotomy in combination with
      distraction osteogenesis have been reported as a safe and successful method to
      obtain good esthetic and functional results, there is a lack of studies
      evaluating this method.Our retrospective study included 12 patients with
      syndromic craniofaciostenosis, who were primarily treated at our department in
      accordance with a standardized treatment protocol, consisting of a simultaneous
      fronto-orbital advancement with LeFort-III osteotomy in combination with a rigid
      external distractor (RED-II). Distraction distance, duration of operation,
      postoperative complications, perioperative hemoglobin concentration, esthetic
      outcome, and the subjective Whitaker Scale were used to evaluate the success of
      our surgical method.The esthetic outcome of all of our patients was assessed as
      good. Furthermore, the surgical outcome was assigned I for 11 patients and II for
      1 patient, who suffered from wound healing disturbance at the left temporal site,
      which required revision 2 weeks postoperatively. The mean skeletal advancement of
      the midface was 16.4 mm, ranging from 12 to 20 mm.Our standardized treatment
      protocol, consisting of fronto-orbital advancement in combination with LeFort-III
      osteotomy and application of a rigid external distractor device (RED-III) for
      patients with severe syndromic craniofaciostenosis, goes along with low infection
      rates and more predictable and precise esthetic and functional outcomes than the
      conventional surgical technique without distraction osteogenesis.

PMID- 29068974
TI  - An atypical lipomatous tumor mimicking a giant fibrovascular polyp of the
      hypopharynx: A case report.
AB  - RATIONALE: Giant fibrovascular polyps (GFVPs) found in the hypopharynx are
      exceedingly rare. These are benign tumors which are identified by CT or MRI and
      usually treated based on symptoms. Even more rarely, pathology may identify one
      of these masses as an atypical lipomatous tumor (ALT). This paper will present a
      case of an ALT of the hypopharynx that was originally classified as a GFVP,
      highlighting the difficulty in distinguishing between them and the importance of
      making the correct diagnosis. PATIENT CONCERNS: An 84-year-old man presented to
      the emergency department with a 6-month history of a pedunculated hypopharyngeal
      growth, dysphagia, and intermittent dyspnea. DIAGNOSES: The mass was
      characterized as a GFVP by barium swallow and MRI. INTERVENTIONS: The
      hypopharyngeal mass was resected for obstructive symptoms and to confirm the
      diagnosis. Final pathology found the mass to be more consistent with an atypical
      lipomatous tumor (ALT). OUTCOMES: The patient's dysphagia and dyspnea resolved.
      He was free of recurrence at 22 months postoperative. LESSONS: Both GFVPs and
      ALTs are very rarely found in the hypopharynx but can be easily misclassified as
      one another. Imaging is useful to initially characterize the mass, but to
      definitively differentiate between them, pathological analysis is necessary.
      Although they are rare, it is important to consider both possibilities on the
      differential for hypopharyngeal masses. Further, accurate analysis is essential
      to distinguish between them because their definitive management and follow-up is
      different.

PMID- 29068975
TI  - Echocardiogram changes following parathyroidectomy for primary
      hyperparathyroidism: A systematic review and meta-analysis.
AB  - The aim of the study is to systematically review the evidence on post
      parathyroidectomy (PTX) changes as measured by echocardiogram (ECHO) in patients
      with primary hyperparathyroidism (PHPT).PHPT may increase risk of cardiovascular
      morbidity/mortality. Conclusions of studies assessing ECHO changes, pre versus
      post PTX, are inconsistent.A systematic literature search was conducted to locate
      published and unpublished studies. Randomized control trials, nonrandomized
      control trials, and observational studies were included. Variables were reported
      as means and standard deviations. An inverse variance statistical method, with
      random-effects analysis model, was applied to continuous data. The effect measure
      was standardized mean difference, confidence interval of 95%. Primary outcome
      measure was left ventricular ejection fraction (LVEF). Secondary outcome measures
      were left ventricular mass index (LVMI), peak early over peak late diastolic
      velocity ratio (E/A ratio), isovolumetric relaxation time (IVRT),
      intraventricular septal thickness (IVST), and posterior wall thickness
      (PWT).Fourteen studies were included. Follow-up time ranged 3 to 67 months. No
      significant differences (P > .05) in primary outcome measure LVEF (SMD = -0.03,
      CI = -0.24, 0.19), or secondary outcome measures E/A Ratio (SMD = -0.05, CI = 
      0.24, 0.14), IVST (SMD = 0, CI = 0.31, 0.32), PWT (SMD = 0.01, CI = -0.38, 0.39),
      LVMI (SMD = -0.18, CI = -0.74, 0.38), and IVRT (SMD = -0.84, CI = -1.83, 0.14)
      were observed.There was no significant difference in LVEF pre to post PTX. Due to
      heterogeneity of current literature, we were unable to determine if other outcome
      measures of cardiac function are affected after PTX in patients with PHPT. We
      recommend a randomized control trial be conducted to make concrete conclusions.

PMID- 29068976
TI  - Diagnostic value of contrast-enhanced CT scans in identifying lung
      adenocarcinomas manifesting as GGNs (ground glass nodules).
AB  - This study aimed to explore the value of contrast-enhanced computed tomography
      (CT) scans in the differential diagnosis of atypical adenomatous hyperplasia,
      adenocarcinoma in situ, minimal invasive adenocarcinoma (MIA), and invasive
      adenocarcinoma (IAC), which manifested as ground glass nodules (GGNs) or mixed
      GGNs.Unenhanced and contrast-enhanced presurgical CT images of 136 cases of GGNs
      were compared. The nodules were diagnosed based on their solid portions and
      maximum dimensions, and the findings obtained using both contrast-enhanced and
      unenhanced CT images were analyzed in corroboration with the pathological
      diagnosis.Most (53/56) preinvasive nodules showed increased mean CT values after
      contrast administration. In the MIA group, after contrast administration,
      enlargements of the solid portions were seen in 48 nodules (48/60), and the
      elevation of the mean CT value was observed in 12 nodules (12/60). The vast
      majority of IAC nodules (29/30) showed enlargement of the solid portions after
      contrast administration. Moreover, for group differences, findings obtained using
      this approach statistically match the pathological findings.Contrast-enhanced CT
      scans are more useful than unenhanced CT scans for the diagnosis of GGNs,
      especially for pure GGNs, before surgery.

PMID- 29068977
TI  - Endotracheal intubation in elective cervical surgery: A randomized, controlled,
      assessor-blinded study.
AB  - BACKGROUND: We compared the effectiveness and safety of endotracheal intubation
      using the GlideScope (GS) video laryngoscope, CTrach laryngeal mask airway (LMA),
      or Shikani optical stylet rigid laryngoscope (SOS) during elective cervical
      surgery. METHODS: Forty-five patients undergoing elective cervical surgery were
      randomly and equally assigned to endotracheal intubation via GS, LMA, or SOS
      airway management. RESULTS: Endotracheal intubation was successfully completed in
      all patients. The mean intubation times of the groups differed significantly (P <
      .01): GS, 17.9 +/- 3.1 s; SOS, 40.4 +/- 13.7 s; and LMA, 80.5 +/- 22.5 s. The
      groups had similar heart rates and mean arterial pressures throughout the
      intubation, except that at 2 minutes after intubation the mean arterial pressure
      of the GS group (106.1 +/- 18.5 mm Hg) was significantly higher than that of the
      LMA (89.7 +/- 18.5 mm Hg) or SOS (89.7 +/- 18.5 mm Hg; P < .01). The change in C2
      5 Cobb angle from baseline was significantly higher in the GS group (GS, 34.2
      degrees  +/- 7.3 degrees ) than the LMA (24.4 degrees  +/- 5.8 degrees ) or SOS
      (25.5 degrees  +/- 6.4 degrees ); P < .01). CONCLUSIONS: The CTrach LMA and SOS
      rigid laryngoscope are effective, safe alternatives to the GS video laryngoscope
      for patients undergoing elective cervical surgery.

PMID- 29068978
TI  - Treatment, prognostic markers, and survival in thymic neuroendocrine tumors: A
      single center experience of 41 patients.
AB  - Neuroendocrine tumors of the thymus (NETTs) are rare but aggressive, and lead to
      poor overall survival. This retrospective study was designed to analyze factors
      that correlate with the prognosis of patients with NETTs.From 1999 to 2015, 41
      ongoing patients with NETTs were enrolled in this study. The clinical data and
      outcome were compiled. Overall survival (OS) rate was analyzed using the Kaplan
      Meier method in univariate analysis and the Cox-model was used in multivariate
      analysis.Of the 41 NETTs patients analyzed (31 male and 10 female), 12 were
      typical carcinoma, 14 were atypical carcinoma, 14 were small-cell carcinoma and,
      1 was large-cell carcinoma. The median follow-up time was 29 months (range, 9.0
      69.0). In total, 25 patients died of cancer-related disease by the last follow
      up. The 3- and 5-year survival rates for all patients were 42.7% and 23.4%,
      respectively. Among the prognostic factors analyzed by multivariate analysis, low
      tumor grade, complete resection, and a negative chromogranin A (CgA) expression
      were positively correlated with survival.The surgical treatment of NETTs, CgA
      negative, and low grade of NETTs were associated with a statistically significant
      better prognosis. However, large, multicenter studies are required to fully
      validate these prognostic factors.

PMID- 29068979
TI  - Trabeculotomy ab interno with Trabectome as surgical management for systemic
      fluoroquinolone-induced pigmentary glaucoma: A case report.
AB  - RATIONALE: Bilateral acute iris transillumination (BAIT) is a poorly-understood
      ocular syndrome in which patients present with acute iridocyclitis and pigmentary
      dispersion with or without ocular hypertension. The etiology of the disease
      remains unknown, though recent reports suggest an antecedent upper respiratory
      tract infection or systemic antibiotic administration may trigger the clinical
      syndrome. PATIENT CONCERNS: A 55-year-old female was referred for a second
      opinion regarding her bilateral ocular pain, photophobia, and ocular
      hypertension. Her medical history was notable for a diagnosis of pneumonia
      managed with oral moxifloxacin several weeks prior to her initial presentation.
      DIAGNOSES: Visual acuity was 20/40 with an intraocular pressure (IOP) of 30 mmHg
      in the affected eye despite maximal tolerated medical therapy. The patient had
      severe bilateral iris transillumination defects with posterior synechiae
      formation and 3+ pigment with rare cell in the anterior chamber. This
      constellation of findings was consistent with a diagnosis of BAIT. INTERVENTIONS:
      A peripheral iridotomy was placed, which mildly relieved the iris bowing, but did
      not affect the IOP or inflammatory reaction. The patient then underwent cataract
      extraction with posterior synechiolysis and ab interno trabeculotomy of the left
      eye with the Trabectome. OUTCOMES: The patient's IOP on the first post-operative
      day was 13 mmHg, and anterior chamber inflammation was noted to be significantly
      reduced at post-operative week 2. The patient was recently seen at a 1-year post
      operative visit and her IOP remains in the low teens on a low-dose combination
      topical agent. LESSONS: Ophthalmologists should remain aware of the association
      between systemic fluoroquinolones and acute pigmentary dispersion that can
      progress to glaucoma. The Trabectome remains a viable option for management of
      pigmentary and uveitic glaucoma resistant to medical treatment.

PMID- 29068980
TI  - Efficacy of dexmedetomidine for pain management in knee arthroscopy: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Dexmedetomidine showed some potential in pain control in patients
      undergoing knee arthroscopy. We conducted a systematic review and meta-analysis
      to explore the efficacy of dexmedetomidine in patients undergoing knee
      arthroscopy. METHODS: We searched the randomized controlled trials (RCTs)
      assessing the effect of dexmedetomidine on knee arthroscopy in PubMed, EMbase,
      Web of science, EBSCO, and Cochrane library databases. The primary outcome was
      pain scores. Meta-analysis was performed using the random-effect model. RESULTS:
      Five RCTs were included. Overall, compared with control intervention in patients
      with knee arthroscopy, dexmedetomidine intervention could significantly reduce
      the pain scores [Std. mean difference = -0.84; 95% confidence interval (95% CI) =
      -1.24 to -0.44; P < .0001] and postoperative diclofenac sodium consumption (Std.
      mean difference = -1.76; 95% CI = -3.32 to -0.21; P = .03), improve duration of
      analgesic effect (Std. mean difference = 1.78; 95% CI = 0.56-3.00; P = .004), but
      showed no influence on hypotension [risk ratio (RR) = 0.93; 95% CI = 0.14-5.92; P
      = .94], bradycardia (RR = 4.93; 95% CI = 0.91-26.58; P = .06), nausea, and
      vomiting (RR = 1.96; 95% CI = 0.31-12.58; P = .48). CONCLUSION: Dexmedetomidine
      intervention was able to significantly reduce the pain scores and postoperative
      diclofenac sodium consumption, and improve duration of analgesic effect in
      patients undergoing knee arthroscopy, but had no influence on hypotension,
      bradycardia, nausea, and vomiting.

PMID- 29068981
TI  - Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma presenting
      with cardiac tamponade: A case report.
AB  - RATIONALE: Primary effusion lymphoma (PEL) is a rare disease of lymphomatous
      effusion in the body cavities in the absence of detectable mass and
      lymphadenopathy. PEL is predominantly related to the immunosuppressed patients
      infected with human herpes virus 8 (HHV-8). PEL-like lymphoma is negative for HHV
      8 and human immunodeficiency virus (HIV) unlike PEL. The pathogenesis and
      prognosis of PEL-like lymphoma are unclear and there is no established treatment
      yet. PATIENT CONCERNS: A 73-year-old male patient was admitted for evaluation of
      dyspnea on exertion with 1-week duration. His relevant examinations were
      completed. DIAGNOSES: PEL-like lymphoma was diagnosed. INTERVENTIONS: The patient
      received chemotherapy including rituximab, cyclophosphamide, doxorubicin,
      vincristine, and prednisolone (R-CHOP), and palliative whole-brain radiotherapy,
      sequentially. OUTCOMES: He died 3 months after the diagnosis. LESSON: Although
      the prognosis of PEL-like lymphoma may be better than PEL, our case showed poor
      disease course despite chemotherapy.

PMID- 29068982
TI  - Delayed recovery of the affected finger extensors at chronic stage in a stroke
      patient: A case report.
AB  - RATIONALE: A 33-year-old male presented with complete weakness of the right
      extremities due to corona radiata infarct. PATIENT CONCERNS: The main concerns of
      the patient is recovery of hand function especially related to finger extension.
      DIAGNOSES: Right corona radiata infarct. INTERVENTIONS: He underwent physical
      therapy and occupational therapy at the outpatient clinic of the rehabilitation
      department of the same university hospital until 2 years after onset. In
      addition, he underwent neuromuscular electrical stimulation for the right finger
      extensors continuously until 4 years after onset. OUTCOMES: At 6 months after
      onset, the weakness of his right side recovered to subnormal state except for the
      right finger extensors which were completely weak. At 1.5 years after onset, the
      right finger extensors began to show slow and continuous recovery. At 4 years
      after onset, the patient showed motor recovery in the right finger extensors to
      the extent that he was able to move against gravity. Discontinuation of the left
      corticospinal tract was observed on 2-month diffusion tensor tractography (DTT);
      however, the integrity of this discontinuation had recovered to the primary motor
      cortex on 4-year DTT. On 2-month transcranial magnetic stimulation (TMS), no
      motor-evoked potential was evoked; in contrast, motor-evoked potentials were
      obtained at the right-hand muscle on 4-year TMS study. LESSONS: We demonstrated
      unusual delayed and long-term recovery of the affected finger extensors in a
      patient with corona radiata infarct using DTT and TMS.

PMID- 29068984
TI  - Diagnostic value of acoustic radiation force impulse imaging for assessing
      superficial lymph nodes: A diagnostic accuracy study.
AB  - The aim of this study was to assess the diagnostic value of acoustic radiation
      force impulse (ARFI) imaging for differentiating superficial lymph nodes.Virtual
      touch tissue imaging (VTI) grade and shear wave velocity (SWV) were analyzed and
      compared in 97 patients (65 women, 32 men; mean age, 49 y; range, 23-72 y) with
      97 lymph nodes [23 chronic nonspecific reactive lymph nodes (CLNs), 38 metastatic
      lymph nodes (MLNs), and 36 blood and lymphatic system diseases lymph nodes
      (BLLNs)]. The elastography characteristics in patients with CLNs, MLNs, and BLLNs
      were compared using the nonparametric Kruskal-Wallis test and Mann-Whitney U test
      for continuous variables and categorical variables. The diagnostic performance of
      VTI grade and SWV were evaluated using the area under the receiver operating
      characteristic curve (AUC).The median of SWV of MLNs was significantly higher
      (2.90 m/s) than those of CLNs (2.15 m/s) and BLLNs (2.52 m/s). The VTI grade of
      MLNs was significantly higher than those of CLNs (P < .001) and BLLNs (P < .001).
      The sensitivity, specificity, accuracy, and AUC were 81.58%, 95.65%, 86.89%, and
      0.904, respectively, at a cutoff level of grade IV for VTI grade in
      differentiating MLNs from CLNs, whereas those of SWV were 57.89%, 86.96%, 68.85%,
      and 0.752, respectively, at a cutoff level of 2.76 m/s.The diagnostic performance
      of VTI grade was significantly higher than that of SWV in differentiating MLNs
      from CLNs. The diagnostic performance of VTI grade and SWV were lower
      intermediate in differentiating MLNs from BLLNs and in differentiating BLLNs from
      CLNs, and there was no significant difference between VTI grade and SWV. ARFI
      imaging may be a feasible method for differentiating MLNs from CLNs.

PMID- 29068983
TI  - Prognostic evaluation of microRNA-210 in various carcinomas: Evidence from 19
      studies.
AB  - BACKGROUND: We performed this meta-analysis to provide a comprehensive evaluation
      of the role of MicroRNA-210 (miR-210) expression on the overall survival (OS)
      rate of cancers. METHODS: We searched for relevant available literatures on miR
      210 and cancer until November 1st, 2016 on the databases PubMed, EMBASE, Cochrane
      Library, and Science Direct database. We calculated the pooled hazard ratio (HR)
      with 95% confidence intervals (CIs) for OS, which compared the high and low
      expression levels of miR-210 in patients of the available studies. Subgroup
      analysis was performed to evaluate the specific role of miR-210 in ethnicity and
      the type of cancers. Publication bias was evaluated using Begg funnel plots and
      Egger regression test. RESULTS: Overall, 19 studies were involved in this meta
      analysis. The result indicated that upregulated miR-210 might be associated with
      poor OS outcome in various carcinomas, with the pooled HR of 1.80 (95% CI: 1.29
      2.51). When stratified by disease, significant results were detected in breast
      cancer (HR = 2.67, 95% CI: 1.24-5.76) and glioma (HR = 2.42, 95% CI: 1.32-4.43).
      Besides, in the subgroup analysis by ethnicity, significant results were detected
      only in Asian populations (HR = 2.14, 95% CI: 1.37-3.34). CONCLUSION: The present
      meta-analysis suggests that high expressed miR-210 is significantly associated
      with OS in cancer patients, which has the potential to be a prognostic marker in
      cancers.

PMID- 29068986
TI  - Association between IRGM polymorphisms and tuberculosis risk: A meta-analysis.
AB  - BACKGROUND: The human immunity-related GTPase M (IRGM) is involved in regulating
      autophagy against invading pathogens. Recently, inconsistent results have been
      reported about the association between IRGM polymorphisms and tuberculosis risk
      in several studies. METHODS: We searched the PubMed, Embase, and Web of
      Knowledge, and extracted data from eligible articles to estimate the associations
      between IRGM polymorphisms (rs10065172, rs4958842, rs4859843, rs4859846, and
      rs72553867) and tuberculosis risk. The pooled odds ratio (OR) with 95% confidence
      intervals (CIs) were calculated using Review manager 5.3. The studies
      heterogeneity was assessed by Cochran Q test. Funnel plot, Begg test, and Egger
      linear regression test were used to evaluate the publication bias. RESULTS: Nine
      case-control studies in 8 articles involving 3780 tuberculosis and 4835 control
      were analyzed. The analysis showed that IRGM rs10065172 and rs4859846 were
      significantly associated with tuberculosis risk in all genetic models whereas the
      latent tuberculosis infection group in 1 study was excluded. However, stratified
      analysis revealed significant associations for IRGM rs10065172 in all genetic
      models among Asians, but not for African/African-Americans. Significant
      associations were observed in recessive and dominant model for rs4958842, allele
      and recessive model for rs4859843, and all genetic models for rs4859846. No
      significant associations between rs72553867 polymorphism and tuberculosis risk
      was identified. Publication bias was detected in allele and additive model of
      rs4859843. CONCLUSIONS: IRGM rs10065172 was associated with decreased risk of
      tuberculosis in Asian populations, but not in African/Africa-Americans.
      rs4958842, rs4859843, and rs4859846, had a large protective effect in Asians,
      whereas rs72553867 was not associated with tuberculosis risk.

PMID- 29068985
TI  - Effects of TRPC1 on epithelial mesenchymal transition in human airway in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: We investigated the effects of TRPC1 on epithelial mesenchymal
      transition (EMT) in human airway in chronic obstructive pulmonary disease (COPD).
      METHODS: A total of 94 patients who underwent lobectomy were selected and divided
      into COPD (49 cases) and control (45 cases) groups. Immunohistochemistry was
      applied to detect expression of E-cadherin and vimentin and TRPC1. Correlation of
      TRPC1 expression with E-cadherin and vimentin expression, and correlations of
      lung function indicators in COPD patients with expression of TRPC1, E-cadherin,
      and vimentin were analyzed. Human airway epithelial cells (16HBE) were used for
      cell experiments; and cigarette smoking extract (CSE) was adopted to establish
      the COPD model using TRPC1 recombinant plasmids and siRNA. Cells were assigned
      into the control, CSE, CSE + vector, CSE + TRPC1, CSE + si-NC, and CSE + si-TRPC1
      groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western
      blot were implemented to detect expression of TRPC1, E-cadherin, and vimentin.
      RESULTS: Compared with the control group, expression of TRPC1 and vimentin
      significantly increased while expression of E-cadherin decreased in the COPD
      group, and protein expression of TRPC1 was positively correlated with the protein
      expression of vimentin but negatively correlated with the protein expression of E
      cadherin. Patients exhibiting positive expression of TRPC1 had lower FEV1,
      FEV1%Pred, and FEV1/FVC, compared with the patients exhibiting negative
      expression of TRPC1. Compared with the control group, expression of TRPC1 and
      vimentin increased, whereas expression of E-cadherin decreased in the CSE, CSE +
      vector, CSE + TRPC1, and CSE + si-NC groups. Compared with the CSE and CSE +
      vector groups, the expression of TRPC1 and vimentin increased but the expression
      of E-cadherin decreased in the CSE + TRPC1 group. Compared with the CSE and CSE +
      si-NC groups, the expression of TRPC1 and vimentin decreased but the expression
      of E-cadherin increased in the CSE + si-TRPC1 group. No significant differences
      were observed among the CSE, CSE + vector and CSE + si-NC groups. CONCLUSION:
      Overexpression of TRPC1 in COPD promoted EMT process and TRPC1 may be a new and
      interesting focus for COPD new treatment in the future.

PMID- 29068987
TI  - Membranous nephropathy in a patient with ankylosing spondylitis: A case report.
AB  - RATIONALE: Renal complications in ankylosing spondylitis (AS) were rarely
      observed, and proteinuria associated with AS can be seen often due to amyloidosis
      in this kind of complications, while membranous nephropathy (MN) is seldom
      considered. This article reports a case of coexistence of AS and MN, to provide
      the exact relationship of these 2 entities and recognized some causes of renal
      involvement in AS. PATIENT CONCERNS: A 44-year-old female presented with pain of
      the left leg for 4 years and pedal edema for 2 weeks. DIAGNOSES: AS was diagnosed
      according to the patient's clinical manifestation and sacroiliitis observed on
      computed tomography (CT) scan. Nephrotic syndrome was found and MN was diagnosed
      according to kidney biopsy in which thickened capillary loops were observed with
      light microscopy, granular deposits of IgG along the capillary wall were observed
      using immunofluorescence staining, and subepithelial electron-dense deposits were
      observed with electron microscopy. No other secondary causes of MN were found on
      extensive investigations. INTERVENTION: Given the diagnoses, the patient received
      nonimmunosuppressive therapy for MN and adalimumab for AS. OUTCOMES: The patient
      got pain relief, as well as urinary protein reduction. LESSONS: This case
      suggested a secondary MN in association with AS and the relationship between
      these 2 diseases needed more concern and further illumination.

PMID- 29068988
TI  - The impact of different surgical procedures on hypoparathyroidism after
      thyroidectomy: A population-based study.
AB  - The main objective of this study is to investigate the outcome between surgical
      procedures and the risk of development of hypoparathyroidism followed by surgical
      procedure in patients with thyroid disorders.We analyzed the data acquired from
      Taiwan's Bureau of National Health Insurance (BNHI) research database from 1998
      to 2011 and found 9316 patients with thyroid surgery. Cox regression model was
      used to calculate the hazard ratio (HR).A count of 314 cases (3.4%) of
      hypoparathyroidism was identified. The 9 years cumulated incidence of
      hypoparathyroidism was the highest in patient undergone bilateral total
      thyroidectomy (13.5%) and the lowest in the patient with unilateral subtotal
      thyroidectomy (1.2%). However, in the patients who had undergone unilateral
      subtotal, the risk was the highest in bilateral total (HR: 11.86), followed by
      radical thyroidectomy with unilateral neck lymph node dissection (HR: 8.56),
      unilateral total (HR, 4.39), and one side total and another side subtotal (HR:
      2.80).The extent of thyroid resection determined the risk of development of
      hypoparathyroidism. It is suggested that the association of these factors is
      investigated in future studies.

PMID- 29068989
TI  - Outcomes of patients with abdominoperineal resection (APR) and low anterior
      resection (LAR) who had very low rectal cancer.
AB  - We compared the oncological outcomes of sphincter-saving resection (SSR) and
      abdominoperineal resection (APR) in 409 consecutive patients with very low rectal
      cancer (i.e., tumors within 3 cm from the anal verge); 335 (81.9%) patients
      underwent APR and 74 (18.1%) underwent SSR. The APR group comprised higher
      proportions of men (67.5% vs 55.4%, P = .049) and advanced-stage patients (P <
      .001). Preoperative chemoradiotherapy (PCRT) was more frequently administered in
      the SSR group (83.8% vs 52.8%, P < .001). Overall, the systemic and local
      recurrence rates were 29.1% and 6.1%, respectively. On stratification according
      to PCRT and pathologic stage, the mode of surgery did not affect the recurrence
      type. Moreover, recurrence-free survival (RFS) did not differ according to the
      mode of surgery in different cancer stages. RFS was associated with ypT and ypN
      stages in patients who received PCRT, while pN stage, lymphovascular invasion
      (LVI), and circumferential resection margin (CRM) involvement were risk factors
      for RFS in those who did not receive PCRT. Notably, SSR was not found to be a
      risk factor for RFS in either subgroup. Patients who were stratified according to
      cancer stage and PCRT also showed no differences in RFS according to the mode of
      surgery. Our results demonstrate that, regardless of PCRT administration, SSR is
      an effective treatment for very low rectal cancer, while CRM is an important
      prognostic factor for patients who did not receive PCRT.

PMID- 29068990
TI  - Aggravation of an injured dentato-rubro-thalamic tract in a patient with mild
      traumatic brain injury: A case report.
AB  - RATIONALE: We report on a patient with mild traumatic brain injury (TBI) by
      follow-up diffusion tensor tractography (DTT), and observed for approximately
      nine monthsby serial diffusion tensor tractography (DTT). PATIENT CONCERNS: A 66
      year-old male patient was injured in a car crash. Approximately four weeks after
      the crash, he developed a tremor in the right hand and leg. His symptoms worsened
      over time. DIAGNOSES: Approximately six months after the crash, he developed a
      mild tremor in the left hand. Nine months after the crash, he manifested severe
      tremor in his right hand, mild resting and intentional tremor in his left hand
      and both legs, and mild trunkal ataxia. INTERVENTIONS: N/A. OUTCOMES: On 3-week
      DTT, well reconstructed DRTTs were observed in both hemispheres, except for the
      thinned lower portion of the right DRTT. On 9-month DTT, the right lower DRTT had
      thinned compared with the 3-week DTT and showed a disruption at the upper
      portion. The left DRTT showed thinning in the lower portion and tearing in the
      upper portion compared with 3-week DTT. LESSONS: Aggravation of an injured DRTT
      was demonstrated in a patient with mild TBI, using serial DTT examination.

PMID- 29068991
TI  - The prescribing trend of oral antidiabetic agents for type 2 diabetes in Taiwan:
      An 8-year population-based study.
AB  - The purpose of this study was to evaluate the prescription trend and pattern of
      oral antidiabetic (OAD) medications, which are extensively used worldwide for
      treating type 2 diabetes, in 2 age groups.In this population-based study, data
      obtained from the National Health Insurance Research Database, Taiwan, were
      analyzed to investigate the prescription trend of all types of OAD medications
      during 2005 to 2012. We used descriptive statistics to demonstrate the trend of
      prescription patterns stratified by age (aged 65 years and above or younger than
      65).Sulfonylurea (SU) was once the most commonly used drug, but the proportion of
      its prescription had declined gradually (76.83% in 2005 to 63.70% in 2012).
      Consequently, biguanide (BG) became the most commonly used drug since 2010
      (64.31% in 2005 to 74.41% in 2012). In addition, the prescriptions of
      thiazolidinedione decreased significantly (9.20% in 2005 to 2.86% in 2012),
      whereas the usage of DPP-4 inhibitor increased with time (3.73% in 2009 to 19.64%
      in 2012). The treatment choice of SU and alpha-glucosidase inhibitor (AGI) was
      higher in elderly patients compared with the younger population (SU: 62.70% in
      2012, AGI: 12.78% in 2012). Two-drug combination therapies were the prevalent
      treatment choices for patients with type 2 diabetes (44.77% in 2012),
      particularly in the elderly group; however, >=3 drug combination therapies
      increased gradually during the study period, particularly in the younger
      group.This descriptive study presents the change in the prescription of OAD
      medication for different age groups during 2005 to 2012.

PMID- 29068992
TI  - Plasma interleukin-27 levels in patients with coronary artery disease.
AB  - Interleukin (IL)-27, one of cytokines in the IL-12 family, is considered to have
      both pro- and anti-inflammatory properties. However, blood IL-27 levels in
      coronary artery disease (CAD) have not been fully elucidated yet. This cross
      sectional study was done to elucidate the association between blood IL-27 levels
      and CAD.We investigated plasma IL-27 and high-sensitivity C-reactive protein
      (hsCRP) levels in 274 consecutive patients who underwent elective coronary
      angiography for suspected CAD. CAD was present in 177 patients [30 acute coronary
      syndrome (ACS) and 147 stable CAD]. Compared with 97 patients without CAD, 177
      patients with CAD had higher IL-27 (median 0.26 vs 0.22 ng/mL, P < .05) and
      higher hsCRP (0.98 vs 0.41 mg/L, P < .001) levels. However, there was no
      significant difference in IL-27 levels among 3 groups of ACS, stable CAD, and
      CAD(-) (0.26, 0.25, and 0.22 ng/mL), whereas hsCRP levels were significantly
      higher in ACS and stable CAD than in CAD(-) (2.09, 0.91 vs 0.41 mg/L, P < .001)
      and were highest in ACS. IL-27 levels tended to increase with the number of >50%
      stenotic coronary vessels: 0.22 in CAD(-), 0.22 in 1-vessel disease, 0.31 in 2
      vessel disease, and 0.27 ng/mL in 3-vessel disease (P < .05). A stepwise increase
      in hsCRP levels was also found: 0.41 in CAD(-), 0.75 in 1-vessel, 1.05 in 2
      vessel, and 1.85 mg/L in 3-vessel disease (P < .001). Plasma hsCRP levels
      significantly (r = 0.35), but IL-27 levels weakly (r = 0.15), correlated with the
      number of stenotic coronary segments. In multivariate analysis, both IL-27 and
      hsCRP levels were independent factors associated with CAD. However, hsCRP, but
      not IL-27, was also a factor for ACS.While plasma IL-27 levels were high in
      patients with CAD, these levels were an independent factor for only CAD, not ACS,
      and weakly correlated with the severity of CAD. Our results suggest that IL-27 is
      unlikely to be a good biomarker reflecting the severity of CAD or the presence of
      ACS, or to play a major role in the progression of CAD.

PMID- 29068993
TI  - Abdominal apoplexy because of the rupture of gastroduodenal artery and inferior
      pancreaticoduodenal artery: A case report.
AB  - RATIONALE: Abdominal apoplexy is a rare and fatal emergency event, which is
      coined as a comparison to the cerebrovascular apoplexy. The exact mechanism of
      abdominal apoplexy was unclear, but arteriosclerosis, hypertension, abdominal
      aneurysm, and other predisposing angiopathy were considered to be the main
      reasons of abdominal apoplexy. The development of the imaging technology gave us
      more opportunities to confirm the diagnosis of abdominal apoplexy. However, the
      diagnosis and identification of the bleeding sites still continued to be a
      challenge. PATIENT CONCERNS: A 55-year-old man presented to the emergency
      department with chief complains of sudden severe abdominal pain. DIAGNOSIS: The
      patient was diagnosed as abdominal apoplexy with 2 synchronous bleeding sites.
      INTERVENTIONS: Angiography confirmed diagnosis of abdominal apoplexy and revealed
      2 synchronous bleeding sites in gastroduodenal artery (GDA) and inferior
      pancreaticoduodenal artery (IPDA). Transcatheter embolization was performed
      immediately. OUTCOMES: The patient recovered and was discharged very soon. Two
      months later, the patient totally recovered and the hematoma disappeared in the
      CT imaging. LESSONS: The reported case is rare, given the very low incidence of
      abdominal apoplexy with 2 synchronous bleeding sites in GDA and IPDA. The
      awareness of abdominal apoplexy was still the key point in the management of this
      disease. Quick diagnosis by the imaging and immediate embolization were very
      important for the treatment.

PMID- 29068994
TI  - Urinary incontinence is associated with the development of peptic ulcers in adult
      women: Data from the KNHANES IV.
AB  - The aim of this study was to investigate the association between urinary
      incontinence (UI) and peptic ulcer (PU) and how this is related to psychological
      stress in Korean women by analyzing the data from the Korea National Health and
      Nutrition Examination Survey IV (KNHANES).A nationally representative sample of
      data on 7475 Korean women >=19 years of age from the KNHANES 2008 to 2010 was
      included. Physician-diagnosed UI and PU were assessed using questionnaires and
      surveys. Psychological stress was assessed through a questionnaire using a 4
      point Likert scale. Data were analyzed using logistic regression to determine the
      association between UI and PU according to the level of psychological stress
      perception.PU was found in 1.41% of the total population. Breaking this down by
      the existence of UI, PU was found in 3.5% of the population with UI, and 1.4% of
      the population without UI, which showed a significant difference. A statistically
      significant trend for increasing prevalence of UI and PU with increasing
      psychological stress perception levels was found among the study population.
      Multivariable logistic regression analyses for PU showed that UI was
      significantly associated with a higher probability of PU in an adjusted model,
      which means that members of the population with UI were more likely to have PU
      than those without UI. A higher level of psychological stress perception was also
      significantly associated with increased odds of PU in the adjusted model.UI could
      potentiate the development of PU through increasing levels of psychological
      stress perception.

PMID- 29068995
TI  - The effect of distraction by dual work on a CPR practitioner's efficiency in
      chest compression: A randomized controlled simulation study.
AB  - BACKGROUND: In the clinical setting, the dispersed practitioners' attention often
      leads to decreased competence in their performance. We aimed to investigate the
      effect of distracted practitioners on the quality of chest compression during
      cardiopulmonary resuscitation. METHODS: A randomized controlled crossover
      simulation study was conducted. Participants were recruited from among doctors,
      nurses, and paramedics working in a university tertiary hospital. The paced
      auditory serial addition test (PASAT) was used as a tool for distracting
      participants. In the crossover design, each participant played 2 scenarios with a
      20-minute time gap, by a random order; 2-minute continuous chest compressions
      with and without PASAT being conducted. The primary outcome was the percentage of
      compression with an adequate compression rate. Secondary outcomes were the
      percentage of compression with adequate depth, the percentage of compression with
      full chest wall recoil, mean compression rate (per minute), mean compression
      depth, and subjective difficulty of chest compression. RESULTS: Forty-four
      participants were enrolled, and all of them completed the study. It was found
      that the percentage of compression with an adequate compression rate was lower
      when the PASAT was conducted. Although there was no difference in the percentage
      of compression with adequate depth (P = .88), the percentage of compression with
      complete chest recoil was lower when PASAT was conducted. In addition, while the
      mean compression rate was higher when PASAT was conducted, the mean compression
      depth was not significantly different (P = .65). The subjective difficulty was
      not different (P = .69). CONCLUSIONS: Health care providers who are distracted
      have a negative effect on the quality of chest compression, in terms of its rate
      and chest wall recoil. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT03124290.

PMID- 29068996
TI  - Diagnostic potential of real-time elastography (RTE) and shear wave elastography
      (SWE) to differentiate benign and malignant thyroid nodules: A systematic review
      and meta-analysis.
AB  - BACKGROUND: Real-time elastography (RTE) and shear wave elastography (SWE) are
      noninvasive and easily available imaging techniques that measure the tissue
      strain, and it has been reported that the sensitivity and the specificity of
      elastography were better in differentiating between benign and malignant thyroid
      nodules than conventional technologies. METHODS: Relevant articles were searched
      in multiple databases; the comparison of elasticity index (EI) was conducted with
      the Review Manager 5.0. Forest plots of the sensitivity and specificity and SROC
      curve of RTE and SWE were performed with STATA 10.0 software. In addition,
      sensitivity analysis and bias analysis of the studies were conducted to examine
      the quality of articles; and to estimate possible publication bias, funnel plot
      was used and the Egger test was conducted. RESULTS: Finally 22 articles which
      eventually satisfied the inclusion criteria were included in this study. After
      eliminating the inefficient, benign and malignant nodules were 2106 and 613,
      respectively. The meta-analysis suggested that the difference of EI between
      benign and malignant nodules was statistically significant (SMD = 2.11, 95% CI
      [1.67, 2.55], P < .00001). The overall sensitivities of RTE and SWE were roughly
      comparable, whereas the difference of specificities between these 2 methods was
      statistically significant. In addition, statistically significant difference of
      AUC between RTE and SWE was observed between RTE and SWE (P < .01). CONCLUSION:
      The specificity of RTE was statistically higher than that of SWE; which suggests
      that compared with SWE, RTE may be more accurate on differentiating benign and
      malignant thyroid nodules.

PMID- 29068997
TI  - Atypical hemolytic uremic syndrome induced by CblC subtype of methylmalonic
      academia: A case report and literature review.
AB  - RATIONALE: Methylmalonic acidemia (MMA) is a common organic acidemia, mainly due
      to methylmalonyl-CoA mutase (MCM) or its coenzyme cobalamin (VitB12) metabolic
      disorders. Cobalamin C (CblC) type is the most frequent inborn error of cobalamin
      metabolism; it can develop symptoms in childhood and often combine multisystem
      damage, which leads to methylmalonic acid, propionic acid, methyl citrate, and
      other metabolites abnormal accumulation, causing nerve, liver, kidney, bone
      marrow, and other organ damage. PATIENT CONCERNS: A 4-year-old girl presented
      with paleness, fatigue, severe normochromic anemia, and acute kidney injury.
      DIAGNOSIS: Based on severe normochromic anemia and acute kidney injury, renal
      biopsy showed membranous proliferative glomerular lesions and thrombotic
      microvascular disease, supporting the diagnosis of aHUS. Although the serum
      vitamin B12 was normal, further investigation found the concentration of urinary
      methylmalonic acid and serum homocysteine increased obviously, genetic analysis
      revealed a heterozygous MMACHC mutation (exonl: c. 80A >G, c. 609G >A). The final
      diagnosis was aHUS induced by inherited methylmalonic acidemia (MMACHC
      heterozygous mutation exonl: c. 80A >G, c. 609G >A). INTERVENTIONS: The patient
      was treated with a 1mg vitamin B12 intramuscular injection daily for 4 days after
      which the dose was then adjusted to a 1mg intramuscular injection twice a week.
      At the same time, the girl was given levocarnitine, betaine, folic acid, along
      with supportive treatment. OUTCOMES: After treated by vitamin B12 for 10 days,
      the patient condition significantly improved, Follow-up results showed complete
      recovery of hemoglobin and renal function. LESSONS: Although the majority of MMA
      onset from neurological damage, our case illustrates that partial CblC-type MMA
      can onset with severe metabolic aHUS. On the basis of chronic thrombotic
      microangiopathy (TMA)-induced renal damage, it can be complicated by acute
      hemolytic lesions. MMA should be considered in those patients with unclear
      microangiopathic hemolytic anemia accompany significant megaloblastic
      degeneration in bone marrow. We should pay attention to the causes and adopt a
      reasonable treatment strategy.

PMID- 29068998
TI  - Survival and complications of stereotactic radiosurgery: A systematic review of
      stereotactic radiosurgery for newly diagnosed and recurrent high-grade gliomas.
AB  - BACKGROUND: Utilization of stereotactic radiosurgery (SRS) for treatment of high
      grade gliomas (HGGs) has been slowly increasing with variable reported success
      rates. OBJECTIVE: Systematic review of the available data to evaluate the
      efficacy of SRS as a treatment for HGG with regards to median overall survival
      (OS) and progression-free survival (PFS), in addition to ascertaining the rate of
      radiation necrosis and other SRS-related major neurological complications.
      METHODS: Literature searches were performed for publications from 1992 to 2016.
      The pooled estimates of median PFS and median OS were calculated as a weighted
      estimate of population medians. Meta-analyses of published rates of radiation
      necrosis and other major neurological complications were also performed. RESULTS:
      Twenty-nine studies reported the use of SRS for recurrent HGG, and 16 studies
      reported the use of SRS for newly diagnosed HGG. For recurrent HGG, the pooled
      estimates of median PFS and median OS were 5.42 months (3-16 months) and 20.19
      months (9-65 months), respectively; the pooled radiation necrosis rate was 5.9%
      (0-44%); and the pooled estimates of major neurological complications rate was
      3.3% (0-23%). For newly diagnosed HGG, the pooled estimates of median PFS and
      median OS were 7.89 months (5.5-11 months) and 16.87 months (9.5-33 months)
      respectively; the pooled radiation necrosis rate was 6.5% (0-33%); and the pooled
      estimates of other major neurological complications rate was 1.5% (0-25%).
      CONCLUSION: Our results suggest that SRS holds promise as a relatively safe
      treatment option for HGG. In terms of efficacy at this time, there are inadequate
      data to support routine utilization of SRS as the standard of care for newly
      diagnosed or recurrent HGG. Further studies should be pursued to define more
      clearly the therapeutic role of SRS.

PMID- 29069000
TI  - Ovarian torsion in children: Development of a predictive score.
AB  - The aim of this study was to identify clinical signs and symptoms of ovarian
      torsion (OT) in children and to develop a simple predictive score.A chart review
      of patients with acute adnexal pathologies treated at the University Children's
      Hospital Basel, Switzerland, between March 2006 and June 2015 was performed.
      Medical records were screened for demographic and clinical data. These included
      clinical symptoms, laboratory studies, imaging, and type of treatment. The
      diagnosis OT was defined as intraoperative visualization of the torsed ovary
      around its pedicle at least 360 degrees. Variables predictive for OT were
      identified and the following score for the likelihood of having OT was developed:
      age (points = number of years) minus 3 points (if vomitus = "yes") and plus 1
      point (if "pain duration >12 hours").A total of 80 patients with acute adnexal
      pathologies were identified. OT was recorded in 17 (21%) cases and ovarian cysts
      (OC) only in 63 (79%) cases. Patients who presented with OT were significantly
      younger than patients with OC only (P = .001). Correspondingly, 11 (65%) of the
      patients with OT had no menarche compared to 3 (5%) patients with OC only (P =
      .001). Vomiting (P = .001), a shorter pain duration (P = .01), and an elevated C
      reactive protein (CRP) (P = .01) were observed significantly more often in
      patients with OT. The sensitivity of a positive OT score was 0.81 and increased
      to 1.00 if restricted to girls between 2 to 12 years of age.The presence of
      vomiting, short duration of abdominal pain, and elevated CRP level have a
      predictive value for the diagnosis of OT. In these patients, an exploratory
      laparoscopy should be conducted without delay. The presented OT score appears to
      be a helpful tool in diagnosing OT in children.

PMID- 29068999
TI  - Prevalence of osteoporosis and related lifestyle and metabolic factors of
      postmenopausal women and elderly men: A cross-sectional study in Gansu province,
      Northwestern of China.
AB  - The aim of this study was to investigate the osteoporosis prevalence and the
      risks of postmenopausal women and elderly men in Gansu province.This cross
      sectional study involved 3359 postmenopausal women and 3205 elderly males who
      were randomly selected from 7 areas in Gansu province. Areal bone mineral density
      (BMD) (g/cm) was measured at the distal one-third radius of the nonstressed
      forearm using dual-energy X-ray absorptiometry (DXA: Osteometer MediTech).
      Factors related to osteoporosis were analyzed.The prevalence of osteoporosis in
      the entire study population was 9.65% for postmenopausal women and 8.08% for
      elderly males by WHO criteria, while the rate of osteopenia were 27.09% for
      postmenopausal women and 26.68% for elderly males. Risk of osteoporosis was
      significantly associated with age, menopause age, duration of menopause, body
      mass index (BMI), educational level, and alcohol consumption in postmenopausal
      women. In elderly men, age, BMI, current smoking, alcohol consumption, physical
      activity, and sun exposure were associated with osteoporosis. The bone turnover
      markers osteocalcin (OC) and C-terminal cross-linked telopeptides of type I
      collagen (beta-CTX) were inversely correlated with BMD in both genders; serum P
      and 25(OH)D found no significant correlation with BMD. Serum Ca showed a positive
      effect on BMD in elderly men only.The osteoporosis prevalence of postmenopausal
      women and the men aged over 60 years in Gansu province is presented. Risk of
      osteoporosis was significantly associated with age, menopause age, year since
      menopause, BMI, and educational level in postmenopausal women. In elderly men,
      age, BMI, and current smoking were associated with osteoporosis. This study also
      found that higher OC and beta-CTX level were associated with lower BMD. Poor
      25(OH)D, Ca, P status were not associated with an increased risk of low BMD.

PMID- 29069002
TI  - The long-term outcomes of recurrent adhesive small bowel obstruction after
      colorectal cancer surgery favor surgical management.
AB  - An adhesive small bowel obstruction (ASBO) is generally caused by postoperative
      adhesions and is more frequently associated with colorectal surgeries than other
      procedures. We compared the outcomes of operative and conservative management of
      ASBO after primary colorectal cancer surgery.We retrospectively reviewed 5060
      patients who underwent curative surgery for primary colorectal cancer; 388 of
      these patients (7.7%) were readmitted with a diagnosis of SBO. We analyzed the
      clinical course of these patients with reference to the cause of their surgery.Of
      the 388 SBO patients analyzed, 170 were diagnosed with ASBO. Their 3-, 5-, and 7
      year recurrence-free survival rates were 86.1%, 72.8%, and 61.5%, respectively.
      The median follow-up period was 59.2 months. Repeated conservative management for
      ASBO without surgical management led to higher recurrence rates: 21.0% after the
      first admission, 41.7% after the second, 60.0% after the third, and 100% after
      the fourth (P = .006). Surgical management was needed for 19.2%, 22.2%, 50%, and
      66.7% of patients admitted with ASBO on the first to fourth hospitalizations,
      respectively. Repeated hospitalization for obstruction led to a greater
      possibility of surgical management (P = .001). Of 27 patients with surgical
      management at the first admission, 6 (17.6%) were readmitted with a diagnosis of
      SBO, but there were no further episodes of SBO in the surgically managed
      patients.Patients who undergo operative management for ASBO have a reduced risk
      of recurrence requiring hospitalization, whereas those with repeated conservative
      management have an increased risk of recurrence and require operative management.
      Operative management should be considered for recurrent SBO.

PMID- 29069003
TI  - Randomized controlled trial of 3 days fasting and oral senna, combined with
      mannitol and simethicone, before capsule endoscopy.
AB  - BACKGROUND AND STUDY AIMS: The approach to small bowel preparation before capsule
      endoscopy (CE) is still suboptimal. PATIENTS AND METHODS: One hundred eighty
      patients were randomly allocated to 3 groups. Patients in Group A took 250 mL 20%
      mannitol and 1 L 0.9% saline orally at 05:00 hours on the day of the procedure.
      In Group B the same preparation was taken at 20:00 on the day before, and at
      05:00 on the day of CE; in addition, 20 mL oral simethicone was taken 30 minutes
      before CE. Group C was treated identically to Group B, except that the patients
      fasted for 3 days and took 3 g senna orally 3 times daily before CE. The length
      of bowel containing green luminal contents was assessed by ImageJ software and
      bowel cleanliness was evaluated by computed assessment of the cleansing score.
      RESULTS: Cleansing of the whole small bowel and the distal small bowel were
      significantly different between the 3 groups (chi = 22.470, P = .000; chi =
      17.029, P = .000, respectively). There were also significant differences between
      the 3 groups in the length of small bowel and specifically the length of the
      distal small bowel containing green luminal contents (chi = 12.390, P = .000, chi
      = 15.141, P = .000, respectively), but not with regard to the proximal small
      bowel (chi = 0.678, P = .509). CONCLUSIONS: Three days fasting and oral senna,
      combined with 20% mannitol and simethicone, before CE, can reduce the effects of
      bile on the small bowel and improve small bowel cleansing, especially in the
      distal small intestine.

PMID- 29069001
TI  - Pre-S deletions of hepatitis B virus predict recurrence of hepatocellular
      carcinoma after curative resection.
AB  - The relationship between hepatitis B virus (HBV) and the prognosis of
      hepatocellular carcinoma (HCC) after surgery remains uncertain. A retrospective
      cohort study was performed to evaluate the impact of pre-S deletions,
      T1762/A1764, and A1896 mutations on prognosis of HCC after curative resection. A
      total of 113 patients with positive serum HBV DNA (>200 IU/mL) who had underwent
      curative resection of pathologically proven HCC were recruited to determine the
      risk factors affecting the prognosis.The median follow-up time was 36.5 months
      and recurrence was detected in 67 patients (59.3%). The cumulative recurrence
      rates and overall survival rates at 1-, 3-, and 5-year after curative resection
      were 18.0%, 49.7%, 70.3%, and 93.7%, 61.0%, 42.5%, respectively. Patients with
      pre-S deletions showed significantly higher recurrence rates compared with those
      with wild type infection (HR: 1.822, P = .018), but not related with a
      significantly poor survival (HR: 1.388, P = .235). Subgroup analysis indicated
      that the patients with type III deletion had significant higher tumor recurrence
      rates than other deletion types (HR: 2.211, 95% confidence intervals [CI]: 1.008
      4.846, P = .048). Multivariate analysis revealed that pre-S deletion, tumor size
      >3 cm in diameter, and the presence of microvascular invasion were independent
      risk factors for tumor recurrence. HBV pre-S deletions were found to be clustered
      primarily in the 5' end of pre-S2 region and were more often found between amino
      acids 120 and 142 of the pre-S2 domain. The domains most frequently potentially
      involved were the transactivator domain in pre-S2 and polymerized human serum
      albumin binding site.Our cohort showed that pre-S deletions at the time of
      resection could predict tumor recurrence in HCC patients after curative
      resection.

PMID- 29069004
TI  - Selection and measurement of control antidepressants in clinical tests for
      Chinese: A systematic review.
AB  - OBJECTIVE: The study aims to help domestic application units and research
      institutions improve their research quality of antidepressant clinical tests by
      studying and analyzing the current status and problems in selecting control drugs
      during domestic antidepressant clinical tests and illustrating some key problems
      that should be noted when selecting the control drug in such researches. METHODS:
      Considering the current domestic and overseas status of control drug selection in
      antidepressant clinical tests, various considerations, and misunderstandings on
      control drug selection in domestic antidepressant clinical tests were clarified
      and described, and possible factors that may influence the absolute effect of
      antidepressants were analyzed. Furthermore, problems that should be noted in
      selecting control drugs for the antidepressant clinical test, especially the
      placebo control, were stated. RESULTS: During the antidepressant clinical
      research, selecting placebo controls conform to moral philosophy and safety
      requirements. To verify the absolute effect of a test drug, a placebo control
      should be set or 3-arm tests should be conducted as far as possible. Possible
      factors that may affect the absolute effect of the test drug, including illness
      severity of the subject at baseline and research scale, should be given
      consideration. CONCLUSIONS: Application units and research institutions should
      consider the selection of subjects, control the failure rate, strengthen safety
      risks, and control and intensify quality control to further improve the overall
      quality and research level of domestic antidepressant clinical tests.

PMID- 29069005
TI  - Effect of polydeoxyribonucleotide injection on pes anserine bursitis: A case
      report.
AB  - RATIONALE: Pes anserine (PA) bursitis is an inflammatory condition of the medial
      knee. The PA bursa becomes more painful when infected, damaged, or irritated.
      Although various treatment options have been attempted to treat PA bursitis,
      optimal treatments are still debated. This study aims to investigate the effect
      of polydeoxyribonucleotide (PDRN) injection on reducing pain and inflammation in
      a patient presenting with PA bursitis. PATIENT CONCERNS: A 50-year-old female
      patient was admitted to our pain clinic with symptoms of tenderness and pain over
      the medial knee. Physical examination revealed the pain to be located over the
      proximal medial tibia at the insertion of the conjoined tendons of the PA. The
      knee had lost its range of movement and strength, and resisted knee flexion.
      DIAGNOSES: She was diagnosed as having PA bursitis. INTERVENTIONS: Ultrasound
      guided PA bursa injection was carried out. OUTCOMES: Follow-up for the patient
      was more than eight months. She showed good improvement in PA bursitis without
      any complications. LESSONS: This is the first successful report of successful
      PDRN injection for PA bursa.

PMID- 29069006
TI  - Malignant changes in adenomyosis in patients with endometrial adenocarcinoma: A
      case series.
AB  - The aim of the study is to describe the clinical characteristics and prognosis of
      malignant transformation of adenomyosis in patients with endometrial cancer.In
      this retrospective descriptive study, the clinical data of patients with
      endometrial cancer (n = 127) who were admitted at our hospital between January
      2006 and December 2013 were evaluated.Among the 127 patients with endometrial
      cancer, 24 patients had endometrial cancer concurrently with adenomyosis. Among
      these 24 patients, 3 were diagnosed with malignant transformation of adenomyosis.
      Postoperative pathological investigations in the cancer+adenomyosis group
      revealed endometrial adenocarcinoma of Grade I (n = 21) and II (n = 3). The
      patients with malignant transformation of adenomyosis were relatively younger
      than the other patients. In those 3 patients, both the estrogen and progesterone
      receptors were strongly expressed in eutopic endometrium and were weakly positive
      in ectopic endometrium.Although adenomyosis is usually benign, it might also be a
      precursor of malignant disease. As the incidence of adenomyosis malignant
      transformation is low, and its clinical manifestations are nonspecific, it may
      only be confirmed by postoperative pathological examination. Further
      investigations on larger sample size may provide additional data about prognosis
      of adenomyosis malignant transformation.

PMID- 29069007
TI  - Successful eltrombopag treatment of severe refractory thrombocytopenia in chronic
      myelomonocytic leukemia: Two cases reports: A CARE-compliant article.
AB  - RATIONALE: Thrombocytopenia in chronic myelomonocytic leukemia (CMML) is usually
      attributed to impaired marrow production resulting from cytotoxic drug use or
      CMML itself ("CMML-induced thrombocytopenia"). In very rare cases, immune
      thrombocytopenia (ITP) can be a complication of CMML ("CMML-associated ITP").
      However, treatment of severe thrombocytopenia in patients with CMML is still a
      challenge. PATIENT CONCERNS: Case 1 was a 61-year-old female patient admitted to
      our hospital because of skin petechiae and purpura for 6 days. She had increased
      monocyte cell count (1.82 * 10/L), markedly decreased platelet count (2 * 10/L),
      hypercellularity of the megakaryocyte lineage with many immature megakaryocytes,
      and ZRSR2(zinc finger CCCH-type, RNA binding motif and serine/arginine rich 2)
      mutation. She failed to the treatment of corticosteroids, intravenous
      immunoglobulin (IVIg), TPO (thrombopoietin), and cyclosporin A (CsA). Case 2 was
      a 72-year-old female patient with thrombocytosis and monocytosis for 4 years, and
      thrombocytopenia for 6 months. After 10 courses of decitabine therapy, she had a
      persistent severe thrombocytopenia and decreased number of megakaryocytes, TET2
      (tet methylcytosine dioxygenase 2) and SRSF2 (serine and arginine rich splicing
      factor 2) mutations were detected. She was dependent on platelet transfusion.
      DIAGNOSES: Case 1 was diagnosed as CMML-associated ITP, and case 2 as CMML with
      decitabine therapy-induced thrombocytopenia. INTERVENTIONS: Both patients were
      treated with eltrombopag. OUTCOMES: In both patients, the platelet counts
      returned to the normal within 1 week after eltrombopag therapy. The platelet
      count in case 1 patient remained stable at 141-200 * 10/L for 20 months with
      stopping therapy for 3 months. In case 2 patient, eltrombopag was stopped 1 month
      later. Her platelet count decreased to 41 * 10/L, but was stable at ~30 * 10/L
      for 3 months with platelet transfusion independency for 12 months. Both patients
      had no adverse effects with eltrombopag. LESSONS: CMML-associated ITP is very
      rare and easily misdiagnosed. To the best of our knowledge, case 1 is the first
      reported case of the successful treatment of CMML-associated ITP with
      eltrombopag. Both CMML-associated ITP and decitabine therapy-induced
      thrombocytopenia in these 2 patients were highly sensitive and safe to
      eltrombopag therapy.

PMID- 29069008
TI  - Mortality prediction using CHADS2/CHA2DS2-VASc/R2CHADS2 scores in systolic heart
      failure patients with or without atrial fibrillation.
AB  - The CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are well-known predictors of stroke
      caused by atrial fibrillation (AF), but no studies have evaluated their use for
      stratifying all-cause mortality risk in patients discharged for systolic heart
      failure (SHF) with or without AF.This study analyzed data in the Taiwan Society
      of Cardiology-heart failure with reduced ejection fraction (TSOC-HFrEF) registry.
      These data were obtained by a prospective, multicenter, observational survey of
      patients treated at 21 medical centers in Taiwan after hospitalization for acute,
      pre-existing or new onset SHF from May, 2013 to October, 2014. During 1 year
      follow-up, 198 patients were lost follow-up, and final 1311 (86.8%) patients were
      included for further analysis. During the follow-up period, 250 (19%) patients
      died. Multivariate analysis revealed that body mass index, thyroid disorder,
      valvular surgery history, chronic kidney disease (CKD), and scores for CHADS2,
      CHA2DS2-VASc, and R2CHADS2 were significant independent predictors of mortality
      in the overall population of SHF patients (all P < .05) The c-indexes showed that
      CHADS2, CHA2DS2-VASc, and R2CHADS2 scores were significantly associated with
      mortality in SHF patients with or without AF (all P < 005). However, R2CHADS2 had
      significantly higher accuracy in predicting mortality in all SHF patients
      compared with CHADS2 and CHA2DS2-VASc (DeLong test, P < .0001), especially in SHF
      without AF (DeLong test, P = .0003).Scores for CHADS2, CHA2DS2-VASc, and R2CHADS2
      can be used to predict 1-year all-cause mortality in SHF patients with or without
      AF. For predicting all-cause mortality in SHF patients, R2CHADS2 is more accurate
      than CHADS2 and CHA2DS2-VASc.

PMID- 29069009
TI  - Oxygen embolism caused by accidental subcutaneous injection of hydrogen peroxide
      during orthopedic surgery: A case report.
AB  - INTRODUCTION: We report a 39-year-old male patient with a fracture of the right
      acetabulum undergoing open reduction and internal fixation with a plate under
      general anesthesia. At closure, the surgeons injected 0.75% ropivacaine into the
      subcutaneous tissue of the incision wound for postoperative analgesia. Soon after
      injection, subcutaneous emphysema at the injection site and a sudden decrease in
      end-tidal CO2 tension with crude oscillatory ripples during the alveolar plateau
      phase were observed. Shortly thereafter, it was found that the surgeons had
      mistakenly injected hydrogen peroxide instead of ropivacaine. Fortunately, the
      patient recovered to normal status after 10 minutes. After the surgery, the
      patient was carefully observed for suspected pulmonary embolism and discharged
      without complications. CONCLUSION: Adverse events related to medication errors
      can occur in operating rooms, and most cases can be prevented through
      communication and verification by medical staff. The use of hydrogen peroxide
      should be reevaluated; when used, medical staff should be aware of the risk of
      oxygen embolism and take extreme care.

PMID- 29069010
TI  - Risk of rash associated with vandetanib treatment in non-small-cell lung cancer
      patients: A meta-analysis of 9 randomized controlled trials.
AB  - BACKGROUND: Vandetanib is a promising anticancer target agent for treating
      advanced carcinomas, such as non-small-cell lung cancer (NSCLC) and breast
      cancer. Rash is a frequently reported adverse event of vandetanib. We conducted
      this meta-analysis to determine the incidence rate and overall risks of all-grade
      and high-grade rash with vandetanib in NSCLC patients. METHODS: PubMed, Embase,
      Web of Science, American Society of Clinical Oncology, and Cochrane Library were
      systematically searched to identify studies with vandetanib and rash in NSCLC
      patients. Data were extracted to calculate the pooled incidence of all-grade and
      high-grade (grade >=3) rash caused by vandetanib treatment. RESULTS: Nine
      randomized controlled trials involving 4893 patients met the inclusion criteria
      and were included in this meta-analysis. The overall incidence of all-grade and
      high-grade rash caused by vandetanib treatment was 46% (95% CI: 37.1%, 54.8%),
      and 3.2% (95% CI: 1.4%, 5.1%), respectively. The risk ratios (RR) of all-grade
      and high-grade rash for vandetanib treatment versus control treatment were 2.35
      (95% CI: 1.20, 4.61; P < .001) and 4.68 (95% CI 1.42, 15.37; P < .001),
      respectively. Subgroup analysis suggested that the increased risk of all-grade
      rash was clear across all subgroups, including first-line/second-line therapy,
      phase 2/phase 3 trial, sample size </>200, a dosage of 100 or 300 mg, and
      monotherapy/combination therapy. However, for the high-grade rash, vandetanib did
      not increase the risk of rash when it was used in first-line therapy, or in a
      phase II trial, or in a trial with sample size <200. CONCLUSIONS: This study
      suggests that vandetanib was associated with a significantly increased risk of
      rash. Therefore, early recognition and appropriate monitoring should be taken
      when NSCLC patients were treated with vandetanib.

PMID- 29069011
TI  - Clinical efficacy of percutaneous nephrolithotomy versus retrograde intrarenal
      surgery for pediatric kidney urolithiasis: A PRISMA-compliant article.
AB  - BACKGROUND: Percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery
      (RIRS) are widely used for pediatric upper tract stones; however, comparisons of
      their clinical efficacies are needed. METHODS: Literature searches for relevant
      articles were performed using PubMed, the Cochrane Central Register of Controlled
      Trials, Embase and the China CNKI database. Study quality was assessed by Jadad
      and Newcastle-Ottawa Scales. Standard mean differences (SMDs) or odds ratios
      (OR), and 95% confidential intervals (95% CIs) were pooled for meta-analysis. In
      addition, data was evaluated the quality of the body of evidence by means of
      grading of recommendations assessment, development, and evaluation (GRADE).
      RESULTS: Data from 4 studies (231 PCNL, 212 RIRS cases) were analyzed. There was
      no significant difference in operation time (SMD: 1.39; 95% CIs: -0.049 to 2.82;
      P = .058), overall stone-free rate (OR: 3.72; 95% CIs: 0.55-25.22; P = .18), or
      complication rate (OR: 1.92; 95% CIs: 0.90-4.07; P = .091). PCNL cases had longer
      hospital stays (SMD: 1.22; 95% CIs: 0.95-1.50; P < .001), but showed a higher
      stone-free rate for stones greater than 20 mm (OR: 6.38; 95% CIs: 1.83-22.22; P =
      .004). For stones less than 20 mm, however, no significant difference between
      PCNL and RIRS was found (OR: 0.92; 95% CIs: 0.33-2.55; P = .87). The quality of
      evidence based on the GRADE system was low. CONCLUSION: Results of our systematic
      review and meta-analysis suggest that, for the treatment of larger kidney stones
      (>20 mm) in pediatric patients, PCNL is a better option due to its higher stone
      free rate, although RIRS may be associated with shorter hospital stays. A large
      scale clinical trial is necessary to validate our findings.

PMID- 29069012
TI  - Is atrial fibrillation a risk factor for normal-tension glaucoma?
AB  - Glaucoma (GL) and atrial fibrillation (AF) are diseases of significant social
      importance. Cardiovascular disorders such as systemic hypertension, hypotension,
      increased blood viscosity, vasospasm, and diabetes are potential risk factors of
      GL, especially when intraocular pressure is not elevated. Only a few studies have
      reported a possible connection between cardiac arrhythmias and GL. The purpose of
      this study was to evaluate the risk of GL in patients with AF.A total of 117
      patients were included in the study, 79 with AF (AF group) and 38 with sinus
      rhythm (Control group), matched for age and sex. The mean +/- standard deviation
      age was 73.6 +/- 7.2 and 71.6 +/- 4.7 years for the AF and control groups,
      respectively. There were no statistically significant differences in the
      percentage of systemic hypertension, congestive heart failure, diabetes mellitus
      type 2, or vascular disease between the groups. Patients were examined for the
      presence of normal-tension glaucoma (NTG) by an ophthalmologist.NTG was confirmed
      in 40 patients (34.2%) in the entire group, with 35 (44.3%) in the AF group and 5
      (13.15%) in the Control group. The incidence of NTG was significantly higher in
      the AF group (P = .0221). Women represented 60% of GL patients in the AF group
      and 80% in the control group. There were no significant differences in
      intraocular pressure between the groups (mean +/- standard deviation, 14.3 +/-
      2.3 vs. 14.2 +/- 2.8 mmHg, P = .4202). Approximately three-fourths of patients
      with AF and NTG had early visual field damage based on the Hodapp
      classification.AF, independent of other known cardiovascular risk factors,
      increases the risk of developing NTG. Many AF patients do not have conspicuous
      symptoms of GL, so understanding the possible risk of its development is critical
      because early detection might help to prevent later visual impairment and even
      irreversible blindness.

PMID- 29069013
TI  - Incidentally polycystic kidney disease identified by SPECT/CT with post-therapy
      radioiodine scintigraphy in a patient with differentiated thyroid carcinoma: A
      case report.
AB  - RATIONALE: Post-therapy or diagnostic whole-body radioiodine scintigraphy is
      widely employed to evaluate the residual, recurrence, or metastases of
      differentiated thyroid carcinoma because of the high sensitivity and accuracy.
      However, it has pitfalls. PATIENT CONCERNS: We described a 63-year-old male with
      a history of papillary thyroid carcinoma who was referred for iodine-131 ablation
      therapy. The post-therapy iodine-131 whole-body images demonstrated abnormal
      increased uptake of the tracer in the regions of bilateral upper abdomen.
      DIAGNOSES: The single photon emission computed tomography/computed tomography
      (SPECT/CT) showed the abnormal Iactivity was corresponded to multiple irregular
      cystic low densities in the both kidneys on the low-dose computed tomography
      images, so the diagnosis of polycystic kidney disease was confirmed.
      INTERVENTIONS AND OUTCOMES: The patient responded well to the lifestyle-based
      treatments. LESSONS: Polycystic kidney disease was one of the etiologies of the
      false-positive findings in the radioiodine scintigraphy.

PMID- 29069014
TI  - Decreased haptoglobin levels inversely correlated with pulmonary artery pressure
      in patients with pulmonary arterial hypertension: A cross-sectional study.
AB  - We investigated the serum haptoglobin levels in patients with pulmonary arterial
      hypertension (PAH) based on the hypothesis that haptoglobin levels would reflect
      subclinical hemolysis due to microangiopathy in pulmonary arterioles.This cross
      sectional study included 3 groups of patients attending Hokkaido University
      Hospital: PAH, chronic thromboembolic pulmonary hypertension (CTEPH), and
      connective tissue diseases (CTD) without PAH (CTD-non-PAH) group. Serum
      haptoglobin levels were measured by standardized turbidimetric immunoassay in all
      patients. Demographic data, laboratory results, right heart catheter, and
      echocardiographic findings were extracted from the medical records. Decreased
      haptoglobin levels were defined as below 19 mg/dL based on the 95th percentile of
      healthy controls.Thirty-five patients in PAH group including 11 with idiopathic
      PAH (IPAH) and 24 with CTD-associated PAH (CTD-PAH), 27 in CTEPH group, and 32 in
      CTD-non-PAH group were analyzed. Serum haptoglobin levels in PAH group (median 66
      mg/dL) were significantly lower than those in CTEPH group (median 94 mg/dL, P =
      .03) and CTD-non-PAH group (median 79 mg/dL, P = .03). The prevalence of
      decreased haptoglobin levels was 26% in PAH group, 15% in CTEPH group, and 6% in
      CTD-non-PAH group. Serum haptoglobin levels had a significant negative
      correlation (r = -0.66, P < .001) with mean pulmonary artery pressure in PAH
      group, particularly in CTD-PAH subgroup (r = -0.74, P < .001), but no correlation
      in IPAH subgroup (r = -0.52, P = .13) and in CTEPH group (r = -0.17, P = .41).
      Follow-up cases of CTD-PAH showed lowering pulmonary artery pressure led to
      normalizing serum haptoglobin levels.Serum haptoglobin levels decreased in PAH
      patients and inversely correlated with pulmonary artery pressure in CTD-PAH
      patients, suggesting their potential as a surrogate marker for CTD-PAH.

PMID- 29069015
TI  - Dynamic enhancement patterns of small-diameter mass-forming intrahepatic
      cholangiocarcinomas on contrast-enhanced magnetic resonance imaging: Challenges
      faced by the radiologist.
AB  - Contrast-enhanced magnetic resonance imaging (MRI) characteristics of small
      diameter mass-forming intrahepatic cholangiocarcinomas (ICCs) (diameter <=3 cm)
      are still unclear.This study focused on imaging findings of small mass-forming
      ICCs. The MRI findings for small-diameter mass-forming ICCs were summarized, and
      the enhancement features of small ICC nodules with different diameters [2 groups
      were defined: a smaller nodule group (ICC diameter <2 cm) and a larger nodule
      group (ICC diameter >2 cm)] were compared on contrast-enhanced MRI.In our study,
      there were 41 small ICC nodules in 41 patients, including 30 men and 11 women
      (average age, 56 years). The nodules were characterized by peripheral
      hyperintense in the arterial phase on contrast-enhanced MRI. In the different
      diameter groups, peripheral hyperintense was the most common in the larger nodule
      group (56% vs 12%, P < .05) and hypointense was more common in the smaller nodule
      group (25% vs 0%, P < .05) in the arterial phase on contrast-enhanced MRI.
      Smaller nodules mainly showed progressive enhancement, whereas larger nodules
      mainly showed peripheral continuous enhancement (56% vs 6%, P < .05).The small
      diameter mass-forming ICC nodules mainly show peripheral continuous enhancement
      on contrast-enhanced MRI; however, those with diameters <2 cm commonly show
      progressive enhancement.

PMID- 29069016
TI  - Topical cryoanesthesia for the relief of pain caused by steroid injections used
      to treat hypertrophic scars and keloids.
AB  - Intralesional steroid injections are the standard treatment for hypertrophic
      scars and keloids. The procedure is, however, quite painful and is unpopular with
      patients because of this. Topical application of anesthetic creams, such as
      Ametop gel (tetracaine) and EMLA cream (lidocaine and prilocaine), has limited
      efficacy because of poor drug penetration. The onset of the analgesic effect is
      also slow, which means that the use of topical anesthetics is time-consuming in
      clinical practice.We hypothesized that a commercially available cryotip could be
      used to provide fast-acting topical cryoanesthesia that would reduce the pain
      associated with steroid injections.Thirty patients with hypertrophic scars or
      keloids were enrolled in the study. Scars were injected with the steroid,
      triamcinolone acetonide, with or without prior application of the cryotip (-10 
      degrees C) for 15 seconds. The degree of pain was evaluated in each case using
      the visual analogue scale (VAS) and the verbal descriptor scale (VDS), together
      with any side-effects caused by application of the cryotip.The VAS pain scores
      showed a statistically significant (P < .01) difference between the pretreated
      and the control scars (pain scores 7.87 +/- 1.31 and 2.7 +/- 1.37, respectively).
      The VDS pain scores also showed a statistically significant (P < .01) difference
      between the pretreated and the control scars. And its average scores were 7.89 +/
      0.32 and 2.68 +/- 0.25, respectively.Application of the cryotip before injection
      could provide a rapid and effective means of reducing the pain associated with
      steroid injections. Painless would result in better therapeutic effect.

PMID- 29069017
TI  - Lymph node dissection and survival in patients with early stage nonsmall cell
      lung cancer: A 10-year cohort study.
AB  - It is still debatable whether complete mediastinal lymph node dissection (MLND)
      is associated with better survival than mediastinal lymph node sampling (MLNS) in
      surgical treatment of nonsmall cell lung cancer (NSCLC). We aimed to assess the
      impact of lymph node dissection on long-term survival among stage I NSCLC
      patients.In this cohort study, 317 stage I NSCLC Chinese patients in Shanghai
      Chest Hospital were followed up for at least 10 years to evaluate the impact of
      different lymph node dissection modes on their survival. Among them, 161 patients
      were in the MLND group and 156 in the MLNS group. Overall survival and median
      survival times were calculated for the 2 groups. The association between lymph
      node dissection and the survival of NSCLC patients was assessed using Cox
      proportional-hazard models.Patients in the MLND group presented better survival
      (median survival time = 154.67 months) than those in the MLNS group (median
      survival time = 124.67 months). The MLNS had higher mortality than the MLND
      group, with the crude hazard ratio of the MLNS group relative to the MLND group
      as 1.32 (95% confidence interval [CI] 0.97, 1.78). After adjusting for age and
      sex, the association between lymph node dissection and mortality (hazard ratio
      1.36, 95% CI 1.00, 1.84) was statistically significant (P = .047). Further
      adjusting for baseline clinical characteristics, the association (hazard ratio
      1.40, 95% CI 1.02, 1.92) remained statistically significant (P = .036). The
      association between lymph node dissection mode and mortality was strong among
      patients with tumor size between 2.0 and 3.0 cm (hazard ratio 2.79, 95% CI 1.45,
      5.37).We found that the MLND was associated with better survival for patients
      with early-stage NSCLC, compared with the MLNS. The effects of MLND on survival
      may depend on tumor size. Our findings have important implications in the
      treatment of early-stage NSCLC. Further prospective studies with a large sample
      size are needed to confirm our findings.

PMID- 29069018
TI  - Thyroid disorders in patients with newly diagnosed rheumatoid arthritis is
      associated with poor initial treatment response evaluated by disease activity
      score in 28 joints-C-reactive protein (DAS28-CRP): An observational cohort study.
AB  - To determine the prevalence of thyroid disorders among newly diagnosed rheumatoid
      arthritis (RA) patients and evaluate the association between clinical
      characteristics of RA and thyroid disorders, and also initial treatment response
      in the RA patients with thyroid disorders.Newly diagnosed, adult RA patients who
      were diagnosed according to the new 2010 American College of
      Rheumatology/European League Against Rheumatism criteria since January 1, 2010,
      were included. Patients' demographic data, serology results including
      immunoglobulin M rheumatoid factor (IgM RF), anticyclic citrullinated peptide
      antibody (anti-CCP), and antinuclear antibody (ANA), and also disease activity
      score in 28 joints-C-reactive protein at the time of diagnosis and after 4 months
      (+/-1-2 months) of treatment initiation were extracted from Danish Danbio
      Registry. Patients' electronic hospital records for the past 10 years were
      reviewed to reveal if they had been diagnosed with thyroid disorders or they had
      abnormal thyroid test.In all, 439 patients were included, female 60.1%, mean age
      64.6 +/- 15.0 years and disease duration 2.6 +/- 1.7 years. Prevalence of thyroid
      disorders was 69/439 (15.7%) and hypothyroidism was the most frequent disorder
      (30.4%). The presence of thyroid disorders among RA patients was significantly
      associated with female sex (P < .001), ANA positivity (P = .04), and anti-CCP
      >=100 EU/mL (P = .05). Furthermore, RA patients with thyroid disorders had
      significantly poorer initial response to RA treatment compared with patients with
      isolated RA after 4 months of treatment (P = .02). There were no associations
      between thyroid disorders and age, disease duration, and also IgM RF
      positivity.Presence of thyroid disorders in RA patients is suggestive of a more
      aggressive disease and poor outcome, with direct effect on initial treatment
      response. To diagnose concurrent thyroid disorders at an earlier stage, routine
      measurement of serum thyroid-stimulating hormone is recommended in all RA
      patients at the time of diagnosis and with yearly interval thereafter.

PMID- 29069019
TI  - End-colostomy diverticulitis with parastomal phlegmon: A case report.
AB  - RATIONALE: Acute colonic diverticulitis is a well-known surgical emergency, which
      occurs in about 10 percent of patients known for diverticulosis. PATIENT
      CONCERNS: The case of a 77-year-old woman is reported, with past history of
      abdominoperineal resection with end-colostomy for low rectal adenocarcinoma, and
      who developed an acute colonic diverticulitis in a subcutaneous portion of
      colostomy with parastomal phlegmon. DIAGNOSES: Initial computed tomography
      imaging demonstrated a significant submucosal parietal edema with local fat
      tissues infiltration in regard of 3 diverticula. INTERVENTIONS: A two-step
      treatment was decided: first a nonoperative treatment was initiated with 2 weeks
      antibiotics administration, followed by, 6 weeks after, a segmental resection of
      the terminal portion of the colon with redo of a new colostomy by direct open
      approach. OUTCOMES: Patient was discharged on the second postoperative day
      without complications. Follow-up at 2 weeks revealed centimetric dehiscence of
      the stoma, which was managed conservatively until sixth postoperative week by
      stomatherapists. LESSONS SUBSECTIONS: Treatment of acute diverticulitis with
      parastomal phlegmon in a patient with end-colostomy could primary be
      nonoperative. Delayed surgical treatment with segmental colonic resection was
      proposed to avoid recurrence and potential associated complications.

PMID- 29069020
TI  - Elevated Th22 cells and related cytokines in patients with epithelial ovarian
      cancer.
AB  - This study is conducted to investigate the involvement of T-helper (Th) cells and
      regulatory T cells in epithelial ovarian cancer (EOC).The percentages of Th22,
      Th17, Th1, and regulatory T cells in the peripheral blood of EOC patients, benign
      ovarian epithelial neoplasm (BOEN) patients, and healthy control (HC) were
      examined by flow cytometry. Enzyme-linked immunosorbent assay was used to
      determine serum levels of interleukin (IL)-22, IL-17, interferon-gamma (IFN
      gamma), and tumor necrosis factor-alpha (TNF-alpha).Th22 and Th17 were
      significantly increased in EOC patients. The plasma concentrations of IL-22 and
      TNF-alpha were significantly elevated in EOC patients compared with BOEN patients
      and HC. In EOC patients, there was an increased trend of Th22, IL-22, and TNF
      alpha in stage III-IV patients compared with stage I-II patients. A positive
      correlation was seen among Th22, Th17, and Th1 cells in EOC patients. Similarly,
      positive correlations were detected between Th22 cells and IL-22 or TNF-alpha and
      between Th1 cells and interferon-gamma (IFN-gamma) in EOC patients. Besides, no
      significant difference was found in Th1 cells and regulatory T cells among EOC
      and BOEN patients and HC.There is a higher circulating frequency of Th22, Th17
      cells, IL-22, and TNF-alpha concentration in EOC patients, which may conjointly
      participate in the pathogenesis and growth of EOC.

PMID- 29069021
TI  - Relapsing polychondritis in a liver transplant recipient: A case report.
AB  - RATIONALE: Relapsing polychondritis (RP) is a multisystemic, progressive disease
      of unknown etiology characterized by recurrent inflammation and progressive
      cartilage destruction. It can involve all types of cartilage including ears and
      nose, tracheobronchial tree, joints, and any other tissue rich in proteoglycans
      such as heart, eyes, and blood vessels. Recurrent chondritis can be life
      threatening if the respiratory tract, heart valves, or blood vessels are
      affected. To date there is no data in the literature on the post solid organ
      transplantation RP. PATIENT CONCERNS: We present a 59-year-old male liver
      transplant recipient with primary sclerosing cholangitis who developed RP of the
      earlobes and nose despite post-transplant immunosuppression. DIAGNOSES: Based on
      the clinical criteria, scintigraphy and biopsy from the left auricle his
      condition was diagnosed as RP. INTERVENTIONS: Pulses of methylprednisolone
      followed by high-dose oral steroids along with azathioprine were administered.
      OUTCOMES: Such therapy diminished local cartilage inflammation, improved
      patient's general condition and the laboratory results. Significant loss of ear
      cartilage and characteristic "saddlenose" were observed after remission of acute
      symptoms. The control scintigraphy proved very good treatment response. LESSONS:
      To the best of our knowledge this is the first report on the RP in liver
      transplant recipient. Based on our patient presentation, we suggest that RP
      should be suspected in any transplant recipient with cartilage inflammation, and
      that the Michet's clinical criteria and scintigraphy seem to be the best
      diagnostic tools for solid organ transplant recipients suspected of RP.

PMID- 29069023
TI  - Stair negotiation in women with fibromyalgia: A descriptive correlational study.
AB  - Walking up and down stairs is a common and important activity of daily living.
      Women with fibromyalgia often show a reduced ability to perform this task.The
      objective of this study was to evaluate the test-retest reliability of stair
      negotiation tasks and to assess the impact of fibromyalgia symptoms on the
      ability to negotiate stairs.Forty-two women with fibromyalgia participated in
      this descriptive correlational study. The relevance of the stair negotiation
      (both walking up and down) was evaluated by assessing its association with the
      revised version of the fibromyalgia impact questionnaire (FIQ-R) and other health
      related variables. Test-retest reliability was also analyzed. The main outcome
      measures were time spent walking up and down stairs and impact of fibromyalgia,
      quality of life, number of falls, weight, and lower limb strength and
      endurance.The intraclass correlation coefficient (ICC) for stair descent was
      0.929 whereas that for ascent was 0.972. The score in these tests correlated
      significantly with the total score for the FIQ-R and the score for many of
      dimensions and symptoms: that is, physical function, overall impact of
      fibromyalgia, pain, energy, stiffness, restorative sleep, tenderness, self
      perceived balance problems, and sensitivity.Given the importance of the stair
      negotiation as activity of daily living and the high reliability, both stair
      ascent and descent tasks may be useful as outcome measures in studies on patients
      with fibromyalgia.

PMID- 29069022
TI  - Prevalence, risk factors, and prognostic significance of masked hypertension in
      diabetic patients.
AB  - The aims of present study were to evaluate the prevalence, risk factors, and
      prognostic significance of masked hypertension in diabetic patients. Using a
      cross-sectional design, 266 patients with documented type 2 diabetes mellitus and
      clinic blood pressure (BP) <140/90 mm Hg without antihypertension treatment were
      enrolled; 24-hour ambulatory BP monitoring was applied to evaluate mean 24-hour
      systolic/diastolic BP. Demographics, medical histories, and medications usage
      were obtained using questionnaire. Fasting venous blood was drawn for biochemical
      analysis. Approximately 26.5% of participants were diagnosed as masked
      hypertension with mean 24-hour systolic BP >130 mm Hg and/or mean 24-hour
      diastolic BP >80 mm Hg. Compared with those without masked hypertension, other
      than significantly higher mean 24-hour systolic/diastolic BP, patients with
      masked hypertension were more elderly, had higher serum glycated hemoglobin
      (HbA1c) and C-reactive protein (CRP) levels and higher prevalence of coronary
      heart disease (CHD). Multivariate regression analysis showed that aging,
      increased HbA1c and CRP levels, and prevalent CHD were independently associated
      with masked hypertension. Logistic regression analysis revealed that after
      adjusted for traditional risk factors including age, male sex, smoking status,
      low-density lipoprotein-cholesterol, CRP, clinic systolic BP, and HbA1c, masked
      hypertension remained independently associated with prevalent cardiovascular
      disease (CVD), with odds ratio of 1.31 and 95% confidence interval of 1.11 to
      1.85. In summary, in diabetic patients, concurrent masked hypertension increases
      the odds of having CVD. Future randomized controlled trials are warranted to
      investigate whether screening and managing masked hypertension could reduce
      cardiovascular events in diabetic patients.

PMID- 29069024
TI  - Risk factors of central lymph node metastasis of papillary thyroid carcinoma: A
      single-center retrospective analysis of 3273 cases.
AB  - Due to the lack of an accurate preoperative diagnostic method of central lymph
      node metastasis (CLNM) of papillary thyroid cancer (PTC), the prophylaxis of
      central lymph node dissection remains controversial. The present study
      investigated the clinicopathological features of PTC patients and the risk
      factors of CLNM. The clinicopathological features of PTC patients with respect to
      sex, age, initial symptoms, observation, tumor diameter, multifocality,
      extrathyroidal invasion, and pathological data combined with other thyroid
      diseases, were analyzed retrospectively. The risk factors of CLNM were analyzed
      by Chi-squared test and multivariate logistic regression model. The CLNM rate of
      PTC was 40.6% (1331/3273). On average, 7.0 (4.0, 12.0) central lymph nodes were
      dissected, and 3.70 (+/-3.8) lymph nodes were proved to be metastatic. Univariate
      analysis showed that sex (P < .001), age (P < .001), tumor diameter (P < .001),
      extrathyroid invasion (P < .001), multifocality (P = .001), concurrent nodular
      goiter (P < .001), initial symptoms (P < .001), and observation or not (P < .001)
      were related to CLNM. The observation time was neither related to CLNM (P = .469)
      nor extrathyroidal invasion (P = .137). Tumors localized in the lower part of the
      thyroid were the risk factors for CLNM (P < .001) while multifocality was
      unrelated (P = .68). The metastasis rate of bilateral multiple regions >
      unilateral multiple regions > single region (P = .003). Multivariate logistic
      regression analysis showed that sex, age, tumor diameter, extrathyroidal
      invasion, and observation were independent risk factors of CLNM. Male, younger
      age, large tumor size, and extrathyroidal invasion were independent risk factors
      for CLNM. CLNM was related to multiple regions occupied by tumors in the thyroid
      but unrelated to multifocality. The tumor occupying a single region and localized
      in the lower part of thyroid could be used as a predictive factor for CLNM. For
      tumors that could not be diagnosed as benign or malignant, observation may be an
      option, since no evidence of disease progression was presented during
      observation.

PMID- 29069026
TI  - Comparison of breast-conserving surgery with mastectomy in locally advanced
      breast cancer after good response to neoadjuvant chemotherapy: A PRISMA-compliant
      systematic review and meta-analysis.
AB  - BACKGROUND: The application of breast-conserving surgery (BCS) on patients with
      locally advanced breast cancer (LABC) with good response to neoadjuvant
      chemotherapy (NACT) still remains controversial. The objective in this study is
      to analyze the safety of BCS in the management of LABC in patients with good
      response to NACT. METHODS: We searched the electronic databases of Medline
      (Pubmed) and Cochrane Library for reports on local recurrence (LR), regional
      recurrence (RR), distant recurrence (DR), 5-year disease-free survival (DFS) or 5
      year overall survival (OS) in patients with LABC receiving BCS or mastectomy (MT)
      and with good response to NACT. Based on the research results, we conducted a
      meta-analysis using Review Manager 5.3. RESULTS: Our study showed that 16 studies
      with a combined total of 3531 patients, of whom 1465 patients underwent BCS,
      whereas 2066 patients underwent MT. There was no significant heterogeneity among
      these studies (Q statistic: P = .88; I = 0%). Patients with good response to NACT
      showed no significant difference in LR and RR [odd ratio (OR) = 0.83; 95%
      confidence interval (CI): 0.60-1.15; P = .26; OR = 0.56; 95% CI: 0.33-0.93; P =
      .03], while we figured out a lower DR (OR = 0.51; 95% CI: 0.42-0.63; P < .01), a
      higher DFS (OR = 2.35; 95% CI: 1.84 to 3.01, P < .01) and a higher OS (OR = 2.12;
      95% CI: 1.51 to 2.98, P < .01) in BCS compared with MT. CONCLUSION: This meta
      analysis concluded that BCS was a safe surgery for patients with LABC and had
      good response to NACT.

PMID- 29069025
TI  - Head and neck cancer associated with increased rate of pulmonary tuberculosis in
      a population-based cohort study.
AB  - The objective of this study was to examine the incidence and hazard ratio (HR) of
      pulmonary tuberculosis in patients with head and neck cancer in Taiwan.This
      population-based retrospective cohort study was conducted to analyze the database
      of the Taiwan National Health Insurance Program. There were 2522 subjects aged 20
      to 84 years with newly diagnosed head and neck cancer as the head and neck cancer
      group between 2000 and 2012, and 10,064 randomly selected sex- and age-matched
      subjects without any cancer as the noncancer group. The incidence of pulmonary
      tuberculosis at the end of 2013 was estimated in both groups. A multivariable Cox
      proportional hazards regression model was used to estimate the HR and 95%
      confidence interval (CI) for pulmonary tuberculosis being associated with head
      and neck cancer.The overall incidence of pulmonary tuberculosis was 2.86-fold
      greater in the head and neck cancer group than that in the noncancer group (4.70
      vs 1.64 per 1000 person-years, 95% CI, 2.53-3.24). After adjusting for
      confounding factors, the adjusted HR of pulmonary tuberculosis became 2.90 for
      the head and neck cancer group (95% CI, 2.11-3.99), compared with the noncancer
      group. In addition, male (adjusted HR 2.27, 95% CI, 1.29-4.00) and age (increase
      for 1 year, adjusted HR 1.06, 95% CI, 1.05-1.08) were associated with pulmonary
      tuberculosis.Head and neck cancer is significantly associated with 2.90-fold
      increased hazard of pulmonary tuberculosis in Taiwan, compared with the general
      population.

PMID- 29069029
TI  - Best option for preoperative biliary drainage in Klatskin tumor: A systematic
      review and meta-analysis.
AB  - The operative treatment combined with preoperative biliary drainage (PBD) has
      been established as a safe Klatskin tumor (KT) treatment strategy. However, there
      has always been a dispute for the preferred technique for PBD technique. This
      meta-analysis was conducted to compare the biliary drainage-related cholangitis,
      pancreatitis, hemorrhage, and the success rates of palliative relief of
      cholestasis between percutaneous transhepatic biliary drainage (PTBD) and
      endoscopic biliary drainage (EBD), to identify the best technique in the
      management of KT.PubMed, EMBASE, and Web of Science were searched systematically
      for prospective or retrospective studies reporting the biliary drainage-related
      cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief
      of cholestasis in patients with KT. A meta-analysis was performed, using the
      fixed or random-effect model, with Review Manager 5.3.PTBD was associated with
      lower risk of cholangitis (risk ratio [RR] = 0.49, 95% confidence interval [CI]:
      0.36-0.67; P < .00001), particularly in patients with Bismuth-Corlette type II,
      III, IV KT (RR = 0.50, 95% CI: 0.33-0.77; P = .05). Compared with EBD, PTBD was
      also associated with a lower risk of pancreatitis (RR = 0.35, 95% CI: 0.17-0.69;
      P = 0.003) and with higher successful rates of palliative relief of cholestasis
      (RR = 1.20, 95% CI: 1.10-1.31; P < .0001). The incidence of hemorrhage was
      similar in these 2 groups (RR 1.29, 95% CI: 0.51-3.27; P = .59). The risk of
      biliary drainage-related cholangitis (RR = 1.96, 95% CI: 0.96-4.01; P = .06) and
      pancreatitis (RR = 1.62, 95% CI: 0.76-3.47; P = .21) was similar between
      endoscopic nasobiliary drainage groups and biliary stenting.In patients with type
      II or type III or IV KT who need to have PBD, PTBD should be performed as an
      initial method of biliary drainage in terms of reducing the incidence of
      procedure related cholangitis, pancreatitis, and improving the rates of
      palliative relief of cholestasis. Well-conducted randomized controlled trials
      with a universial criterion for PBD are required to confirm these findings.

PMID- 29069028
TI  - Factors associated with severe sepsis or septic shock in complicated
      pyelonephritis.
AB  - Severe sepsis or septic shock are the main factors influencing the prognosis of
      acute pyelonephritis (APN). Our aim was to analyze factors associated with the
      development of severe sepsis or septic shock in a large sample of patients with
      acute complicated pyelonephritis (ACPN).This prospective observational study
      comprised 1507 consecutive patients aged 14 years or older who were admitted to a
      tertiary care hospital because of ACPN between 1997 and 2015. Covariates
      associated in univariate analysis with severe sepsis or septic shock were then
      analyzed by multivariate logistic regression.Of the 1507 patients, 423 (28.1%)
      fulfilled the criteria for severe sepsis or septic shock at the time of
      admission. Crude and attributable mortality at 30 days were 17.7% and 11.7% in
      patients with severe sepsis or septic shock versus 1.7% and 0.6% in patients
      without severe sepsis or septic shock, P < .0001 and P < .0005, respectively. An
      age > 65 years, urinary instrumentation in the previous 2 weeks, the lack of
      mictional syndrome or costovertebral tenderness, an ectasia >= grade II, and
      bacteremia were independent risk factors associated with severe sepsis or septic
      shock.The prevalence of severe sepsis and septic shock in patients with ACPN is
      high. Some factors associated with severe sepsis are easy to identify in any
      emergency department. The information provided here could be useful when deciding
      which patients should be admitted to receive immediate treatment.

PMID- 29069031
TI  - Clinical manifestations and treatment outcomes of syphilitic uveitis in HIV
      negative patients in China: A retrospective case study.
AB  - Syphilitic chorioretinitis should be included in differential diagnosis of any
      form of ocular inflammation. A significantly higher proportion of human
      immunodeficiency virus (HIV)-positive patients with ocular syphilis as compared
      to HIV-negative cases have been reported in published studies. However, the
      clinical signs and symptoms are more insidious in HIV-negative patients who are
      easily misdiagnosed. We report a series of cases of ocular syphilis and describe
      the clinical manifestations and treatment outcomes of syphilitic chorioretinitis
      in HIV-negative patients in China.This was a retrospective case series study. The
      clinical records of patients with syphilis chorioretinitis were reviewed.
      Demographic information and findings of fundus fluorescein angiography (FFA),
      indocyanine green angiography (ICGA), and spectral domain optical coherence
      tomography (SD-OCT) were analyzed. All patients received the standard treatment.
      Ophthalmology examination and laboratory evaluation were repeated every 3 months.
      All changes were recorded. The treatment was considered successful if the
      patients had no inflammation in both eyes and rapid plasma reagin titer was
      negative after therapy.The study examined 41 eyes of 28 HIV-negative patients.
      The main complaints were blurry vision, floaters, and visual field defect. Twenty
      seven eyes presented with panuveitis, and all had posterior involvement,
      including uveitis, vasculitis, chorioretinitis, and optic neuritis. The most
      common manifestations were uveitis and retinal vasculitis. Disc hyperfluorescence
      and persistent dark spots were the most common findings on FFA and ICGA. The ill
      defined inner segment/outer segment junction was the most frequent manifestation
      on SD-OCT. Patients were diagnosed with syphilitic uveitis based on positive
      serological tests. Best-corrected visual acuity (BCVA) was improved in 34 eyes
      after treatment. Eleven patients were misdiagnosed before serological tests were
      performed. The delay in treatment led to long-standing cystoid macular edema and
      optic neuropathy, which were associated with poor BCVA (P = .037).The common
      manifestations of syphilitic chorioretinitis were uveitis, retinal vasculitis,
      and optic neuritis. Further diagnosis should be prompted by FFA, ICGA, and SD-OCT
      when ocular manifestation is suspected. The standard treatment for neurosyphilis
      was effective. If patients are presumed to be in low-risk groups such as HIV
      negative, delays in diagnosis, and therapy may be likely. It is necessary to
      reiterate the importance of including syphilis uveitis as a differential
      diagnosis for any form of ocular inflammations, especially posterior uveitis and
      optic neuropathy.

PMID- 29069030
TI  - Clinical outcomes of peripartum cardiomyopathy: a 15-year nationwide population
      based study in Asia.
AB  - Peripartum cardiomyopathy (PPCM) is the development of heart failure during late
      pregnancy to months postpartum with potential fatal outcome. However, the disease
      is not well-studied in Asia.We aimed to investigate the epidemiology and clinical
      outcomes of PPCM in Taiwan.Electronic medical records were retrieved from Taiwan
      National Health Insurance Research Database from 1997 to 2011. Patients with PPCM
      were separated into 3 groups based on the timing of diagnosis. Early: PPCM
      diagnosed first to ninth month of pregnancy. Traditional: PPCM diagnosed last
      month of pregnancy till fifth month post-delivery. Late: PPCM diagnosed sixth to
      twelfth month post-delivery. Primary outcomes defined as cardiac death, all-cause
      mortality, and major adverse cardiovascular events (MACE) within 1 year.A total
      of 3,506,081 deliveries during 1997 to 2011 were retrieved and 925 patients with
      PPCM were identified. Overall incidence of PPCM was 1:3,790 during the 15 years.
      Early, Traditional, and Late group each had 88, 742, and 95 patients. Cardiac
      death occurred in 31 patients, all-cause mortality in 72 patients, and MACE in 65
      patients. Late group had 2- to 3-fold event rates in cardiac death, all-cause
      mortality, and MACE compared with Early and Traditional groups. Cumulative
      incidence showed significant differences for cardiac death (P = .0011), all-cause
      mortality (P = .0031), and MACE (P = .0014) among 3 groups. Multivariate Cox
      model showed Late group had significantly worse outcomes after adjusted for
      clinical variables compared with 2 other groups.Our study is the largest national
      cohort among Asian countries that showed timing of diagnosis of PPCM had
      different outcomes. Late diagnosis portended significantly increased morbidity
      and mortality, even after adjusted for clinical variables.

PMID- 29069027
TI  - The combined effects of genetic risk and perceived discrimination on blood
      pressure among African Americans in the Jackson Heart Study.
AB  - Both genomics and environmental stressors play a significant role in increases in
      blood pressure (BP). In an attempt to further explain the hypertension (HTN)
      disparity among African Americans (AA), both genetic underpinnings (selected
      candidate genes) and stress due to perceived racial discrimination (as reported
      in the literature) have independently been linked to increased BP among AAs.
      Although Gene x Environment interactions on BP have been examined, the
      environmental component of these investigations has focused more on lifestyle
      behaviors such as smoking, diet, and physical activity, and less on psychosocial
      stressors such as perceived discrimination.The present study uses candidate gene
      analyses to identify the relationship between Everyday Discrimination (ED) and
      Major Life Discrimination (MLD) with increases in systolic BP (SBP) and diastolic
      BP (DBP) among AA in the Jackson Heart Study. Multiple linear regression models
      reveal no association between discrimination and BP after adjusting for age, sex,
      body mass index (BMI), antihypertensive medication use, and current smoking
      status.Subsequent candidate gene analysis identified 5 SNPs (rs7602215,
      rs3771724, rs1006502, rs1791926, and rs2258119) that interacted with perceived
      discrimination and SBP, and 3 SNPs (rs2034454, rs7602215, and rs3771724) that
      interacted with perceived discrimination and DBP. Most notably, there was a
      significant SNP * discrimination interaction for 2 SNPs on the SLC4A5 gene:
      rs3771724 (MLD: SBP P = .034, DBP P = .031; ED: DBP: P = .016) and rs1006502
      (MLD: SBP P = .034, DBP P = .030; ED: DBP P = .015).This study supports the idea
      that SNP * discrimination interactions combine to influence clinically relevant
      traits such as BP. Replication with similar epidemiological samples is required
      to ascertain the role of genes and psychosocial stressors in the development and
      expression of high BP in this understudied population.

PMID- 29069032
TI  - Laparoscopic associating liver tourniquet and portal ligation combined rescue
      transhepatic arterial embolization for staged hepatectomy: A case report.
AB  - RATIONALE: Staged hepatectomy is an important surgical method for large
      hepatocellular carcinoma (HCC). However, the insufficient future liver remnant
      (FLR) is still the major barrier in stage II hepatectomy. We herein reported a
      case of laparoscopic associating liver tourniquet and portal ligation combined
      rescue transhepatic arterial embolization (TAE) for staged hepatectomy. PATIENT
      CONCERNS: Laparoscopic associating liver tourniquet and portal ligation for
      staged hepatectomy (ALTPS) was performed for cirrhotic HCC in stage I. To
      stimulate the growth of FLR, a "rescue" TAE was initiated before stage II.
      DIAGNOSE: HCC with hepatitis B cirrhosis. OUTCOMES: Two weeks later after TAE,
      the FLR achieved sufficient hypertrophy and stage II surgery was successfully
      performed. The patient was discharged 7 days after the second stage without
      serious complication. During the follow-up at postoperative 6 months, the patient
      underwent radiofrequency ablation, because contrast-enhanced ultrasonography
      showed 1 cm tumor recurrence in the remnant liver. LESSONS: Rescue TAE plays an
      important role to stimulate the increasing of FLR after ALTPS.

PMID- 29069033
TI  - Postrenal acute kidney injury in a patient with unilateral ureteral obstruction
      caused by urolithiasis: A case report.
AB  - RATIONALE: In patients with bilateral ureteral obstruction, the serum creatinine
      levels are often elevated, sometimes causing postrenal acute kidney injury (AKI).
      In contrast, those with unilateral ureteral obstruction present normal serum
      creatinine levels, as long as their contralateral kidneys are preserved intact.
      However, the unilateral obstruction of the ureter could affect the renal
      function, as it humorally influences the renal hemodynamics. PATIENT CONCERNS: A
      66-year-old man with a past medical history of hypertension and diabetes mellitus
      came to our outpatient clinic because of right abdominal dullness. DIAGNOSES:
      Unilateral ureteral obstruction caused by a radio-opaque calculus in the right
      upper ureter and a secondary renal dysfunction. INTERVENTIONS: As oral hydration
      and the use of calcium antagonists failed to allow the spontaneous stone passage,
      extracorporeal shock wave lithotripsy (ESWL) was performed. OUTCOMES: Immediately
      after the passage of the stone, the number of red blood cells in the urine was
      dramatically decreased and the serum creatinine level almost returned to the
      normal range with the significant increase in glomerular filtration rate.
      LESSONS: Unilateral ureteral obstruction by the calculus, which caused reflex
      vascular constriction and ureteral spasm in the contralateral kidney, was thought
      to be responsible for the deteriorating renal function.

PMID- 29069034
TI  - One-stage posterior excision of lumbosacral hemivertebrae: Retrospective study of
      case series and literature review.
AB  - Lumbosacral hemivertebrae causes unique problems as early trunk decompensation
      and long compensatory curve above. There are only a few reports on it. This case
      series is a fair supplement in the literatures.To evaluate the clinical and
      radiological outcomes of lumbosacral hemivertebrae resection through 1-stage
      posterior approach.Between 2005 and 2014, a consecutive series of congenital
      scoliosis due to lumbosacral hemivertebrae underwent hemivertebrae excision
      through 1-stage posterior only approach. Demographic, operative, radiological,
      and quality of life data were reviewed.The mean lumbosacral curve was 29 +/- 7
      degrees  preoperatively, 10 +/- 3 degrees  postoperatively, and 13 +/- 5 degrees 
      at the final follow up. The final correction rate was 55 +/- 9%. The gravity
      trunk shift was 11 +/- 3 mm preoperatively, 37 +/- 12 mm (range, 6-49 mm)
      postoperatively, 14 +/- 9 mm at final follow up. The rib cage shift was 36 +/- 12
      mm preoperatively, 19 +/- 5 mm postoperatively, and 15 +/- 4 mm at the final
      follow up. The mean blood loss was 527 +/- 125 mL and the mean surgery time was
      336 +/- 98 minutes. The mean follow up period was 41 +/- 6 months. Two patients
      underwent transient neurological complications, 2 had wound bad healing, and 1
      got wound infection. No pseudoarthrosis and instrumentation failure was
      observed.One-stage posterior hemivertebrae excision could gain reasonable
      outcome. It is crucial to completely resect the hemivertebrae and the Y-shaped
      disc. Bending the rod to appropriate lordosis is helpful to close the convex
      side. Early surgical intervene is a preferred choice to restore the trunk balance
      and avoid extensive fusion. The neurological complication rate is high. Convex
      radiculopathy is often caused by retraction, it could recover at follow up.

PMID- 29069035
TI  - Low-intensity pulsed ultrasound promotes endothelial cell-mediated osteogenesis
      in a conditioned medium coculture system with osteoblasts.
AB  - Angiogenesis plays an important role during bone regeneration. Low-intensity
      pulsed ultrasound (LIPUS) has been proven to accelerate the process of bone
      fracture healing. However, the mechanism of the effect of LIPUS on bone
      regeneration is still unclear. In the present study, we used human umbilical vein
      endothelial cell (HUVEC) and human osteosarcoma cell (MG-63) to investigate the
      effect of LIPUS stimulation in an endothelial cell-osteoblast coculture system.
      At the same time, we used transwell and in vitro angiogenesis assay to observe
      how LIPUS affects endothelial cells. The results demonstrated that LIPUS could
      significantly increase the migratory ability and promote tube formation in
      angiogenesis of HUVECs. Furthermore, LIPUS could significantly elevate the
      expression of osteogenesis-related genes on osteoblasts such as Runt-related
      transcription factor 2, alkaline phosphatase, Osteorix, and Cyclin-D1, indicating
      the pro-osteogenesis effect of LIPUS in our coculture system. In conclusion,
      endothelial cell is involved in LIPUS-accelerated bone regeneration, the positive
      effect of LIPUS may be transferred via endothelial cells surrounding fracture
      healing site.

PMID- 29069036
TI  - Communication skills in pediatrics - the relationship between pediatrician and
      child.
AB  - Interpersonal and communication skills are 2 essential qualities of every
      physician. These are separate and distinct parts of the professional character of
      every physician. In pediatrics these abilities present even a higher impact.We
      performed a survey-type prospective study based on questionnaires on 100
      subjects, equally divided into 4 groups: 25 children, 25 pediatricians, 25 care
      givers (parents, tutors, and relatives), and 25 health care staff, in a Tertiary
      Pediatric Clinic from Romania, between January 2017 and April 2017.We included
      100 participants in our study, equally divided into 4 groups: pediatric patients,
      pediatricians, care-givers, and health care staff. The 1st group comprised 25
      children diagnosed with different chronic conditions, presenting the age between
      5 and 14 years. The male gender predominated among the children (57%). The lowest
      general average score for "Communication" section was encountered among
      pediatricians group, 3.8, while the other 3 groups presented the same average
      score for this section, that is, 4.6. The children and the health care staff
      offered the same average score for "Transparency," that is, 4.6, while the
      pediatricians offered a score of 4.5, and the care-givers of 4.7. The lowest
      average score for the item "Hospital environment" was given by the doctors, that
      is, 3.3, followed by care-givers with a score of 3.6, health care staff 3.7, and
      children with an average score of 3.8. All the 4 groups included in the study
      offered a general average of 4.9 out of 5 for the "Intercultural issues" section.
      The lowest average score for "Time management" section was offered by both
      children and pediatricians, that is, 4.1, while care-givers and health care staff
      had a slightly better perception regarding this item, offering 4.2 and 4.3,
      respectively.The opinion among the 4 groups included in the study was generally
      similar regarding the 5 items assessed by our questionnaires. Therefore, the main
      aspects that need to be improved in the health care system in downward order are
      the following: hospital environment, time management, communication,
      transparency, and intercultural issues.

PMID- 29069037
TI  - Dopamine versus norepinephrine in the treatment of cardiogenic shock: A PRISMA
      compliant meta-analysis.
AB  - BACKGROUND: Guidelines recommend that norepinephrine (NA) should be used to reach
      the target mean arterial pressure (MAP) during cardiogenic shock (CS), rather
      than epinephrine and dopamine (DA). However, there has actually been few studies
      on comparing norepinephrine with dopamine and their results conflicts. These
      studies raise a heat discussion. This study aimed to validate the effectiveness
      of norepinephrine for treating CS in comparison with dopamine. METHODS: We
      performed a meta-analysis of randomized controlled trials (RCTs) to assess pooled
      estimates of risk ratio (RR) and 95% confidence interval (CI) for 28-day
      mortality, incidence of arrhythmic events, gastrointestinal reaction, and some
      indexes after treatment. RESULTS: Compared with dopamine, patients receiving
      norepinephrine had a lower 28-day mortality (RR 1.611 [95% CI 1.219-2.129]; P <
      .001; P heterogeneity = .01), a lower risk of arrhythmic events (RR 3.426 [95% CI
      2.120-5.510]; P < .001; P heterogeneity = .875) and a lower risk of
      gastrointestinal reaction (RR 5.474 [95% CI 2.917-10.273]; P < .001; P
      heterogeneity = 0). In subgroup analyses on 28-day mortality by causes of CS,
      there were more benefits from norepinephrine than dopamine in 2 subgroups.
      CONCLUSIONS: Our analysis revealed that norepinephrine was associated with a
      lower 28-day mortality, a lower risk of arrhythmic events, and gastrointestinal
      reaction. No matter whether CS is caused by coronary heart disease or not,
      norepinephrine is superior to dopamine for correcting CS on the 28-day mortality.

PMID- 29069038
TI  - Esophageal foreign body ingestion in adults on weekdays and holidays: A
      retrospective study of 1058 patients.
AB  - The purpose of this study is to compare the clinicopathological characteristics
      and outcomes of esophageal foreign body (FB) ingestion in adults between weekdays
      and holidays. This is a retrospective study including 1058 patients with
      esophageal FB ingestion from 2012 to 2016. Patient characteristics, the types and
      locations of FB, and clinical outcomes were compared between patients on weekdays
      and holidays. Furthermore, independent risk factors of complication on weekdays
      and holidays respectively were evaluated. The locations of FB, underlying
      diseases, and complications significantly differed between weekdays and holidays
      groups, while no difference was found in the types of FB. Patients got higher
      percentage of erosion complication on holidays than that on weekdays (60.8% vs
      47.6%, P < .0001). Multivariate logistic regression analysis revealed that jujube
      shell was a significant predictor of complication on weekdays (P < .001).
      However, complication was significantly associated with nonfood bolus FB
      ingestion on holidays (P < .001). Our data suggest that there were different
      clinicopathological characteristics of FB ingestion between weekdays and
      holidays, and more patients got complications on holidays. On holidays, a latex
      protector hood or an overtube should be applied to patients who swallowed nonfood
      bolus in order to reduce esophageal mucosal damage.

PMID- 29069039
TI  - Neoadjuvant modified-FOLFIRINOX followed by surgical resection of both the
      primary and metastatic tumors of a pancreatic hepatoid carcinoma with synchronous
      liver metastasis: A case report.
AB  - RATIONALE: Pancreatic hepatoid carcinoma (PHC) is a rare form of pancreatic
      malignancy mimicking hepatocellular carcinoma (HCC) in morphology,
      immunohistochemistry, and behavior. PHC usually has an aggressive clinical course
      and poor prognosis. Effective treatment strategies are lacking due to poor
      understanding and extreme rarity of such kind of malignancy. PATIENT CONCERNS::
      we present the case of a 75-year-old man with tumors in the liver and the tail of
      pancreas that were detected in a routine health check-up. DIAGNOSES: Pancreatic
      hepatoid carcinoma with liver metastasis INTERVENTIONS:: The patient was treated
      by neoadjuvant modified-FOLFIRINOX (mFOLFIRINOX) chemotherapy and subsequent
      resection of both the primary pancreatic tumor and the sole liver metastasis.
      OUTCOMES: Pathology findings confirmed complete pathological response of the
      liver metastatic tumor and partial response of the primary pancreatic tumor to
      neoadjuvant mFOLFIRINOX. Adjuvant chemotherapy with mFOLFIRINOX was given and
      until now the patient has a progression-free survival of 13 months after
      diagnosis. LESSONS: PHC are often associated with early liver metastasis and a
      poor prognosis, surgical resection combined with neoadjuvant and adjuvant
      FOLFIRINOX chemotherapy is proved to be efficient in such kind of malignancy,
      even with liver metastasis.

PMID- 29069040
TI  - Predictive validity of the ACS-NSQIP surgical risk calculator in geriatric
      patients undergoing lumbar surgery.
AB  - The risk calculator of the American College of Surgeons National Surgical Quality
      Improvement Program (ACS-NSQIP) has been shown to be useful in predicting
      postoperative complications. In this study, we aimed to evaluate the predictive
      value of the ACS-NSQIP calculator in geriatric patients undergoing lumbar
      surgery.A total of 242 geriatric patients who underwent lumbar surgery between
      January 2014 and December 2016 were included. Preoperative clinical information
      was retrospectively reviewed and entered into the ACS-NSQIP calculator. The
      predictive value of the ACS-NSQIP model was assessed using the Hosmer-Lemeshow
      test, Brier score (B), and receiver operating characteristics (ROC, also referred
      C-statistic) curve analysis. Additional risk factors were calculated as surgeon
      adjusted risk including previous cardiac event and cerebrovascular
      disease.Preoperative risk factors including age (P = .004), functional
      independence (P = 0), American Society of Anesthesiologists class (ASA class, P =
      0), dyspnea (P = 0), dialysis (P = .049), previous cardiac event (P = .001), and
      history of cerebrovascular disease (P = 0) were significantly associated with a
      greater incidence of postoperative complications. Observed and predicted
      incidence of postoperative complications was 43.8% and 13.7% (+/-5.9%) (P < .01),
      respectively. The Hosmer-Lemeshow test demonstrated adequate predictive accuracy
      of the ACS-NSQIP model for all complications. However, Brier score showed that
      the ACS-NSQIP model could not accurately predict risk of all (B = 0.321) or
      serious (B = 0.241) complications, although it accurately predicted the risk of
      death (B = 0.0072); this was supported by ROC curve analysis. The ROC curve also
      showed that the model had high sensitivity and specificity for predicting renal
      failure and readmission.The ACS-NSQIP surgical risk calculator is not an accurate
      tool for the prediction of postoperative complications in geriatric Chinese
      patients undergoing lumbar surgery.

PMID- 29069042
TI  - The radiological findings of hypoglycemic encephalopathy: A case report with high
      b value DWI analysis.
AB  - RATIONALE: Hypoglycemic encephalopathy is a metabolic encephalopathy. Clinical
      risk is mixed with acute cerebrovascular disease, so it is critical to identify
      and make the correct diagnosis of the disease as early as possible. PATIENT
      CONCERNS: Here, we report a case of a 51-year-old male patient with hypoglycemic
      encephalopathy, who presented confusion and unconsciousness for 1 day. DIAGNOSES:
      In addition to blood-related indicators and medical histories, magnetic resonance
      imaging (MRI), especially diffusion-weighted imaging (DWI), can be valuable to
      the diagnosis of hypoglycemic encephalopathy, which showed diffuse high-signal
      intensity in the cerebral cortex, and also the hippocampus, head of the caudate
      nucleus, the lentiform nucleus, and corpus callosum. INTERVENTIONS: Intravenous
      glucose injection and drip was performed repeatedly. The blood glucose levels
      were gradually corrected, and the resulting blood glucose was 6.5 mmol/L.
      OUTCOMES: The prognosis depends on the degree of hypoglycemia, duration, and
      condition of the organism. Due to the long duration of hypoglycemia,
      unfortunately, the patient died. LESSONS: It is critical to diagnose hypoglycemic
      encephalopathy as early as possible. MRI reveals diffuse abnormal intensity in
      the cortex and basal ganglia region. DWI using high b values provides important
      information for diagnosis.

PMID- 29069041
TI  - Effects of fiber and probiotics on diarrhea associated with enteral nutrition in
      gastric cancer patients: A prospective randomized and controlled trial.
AB  - BACKGROUND AND OBJECTIVES: Diarrhea is a common complication of enteral nutrition
      (EN), which affects recovery and prolongs the length of hospital stay (LOHS). To
      investigate the effect of fiber and probiotics in reducing diarrhea associated
      with EN in postoperative patients with gastric cancer (GC), the authors designed
      this prospective randomized-controlled trial. METHODS AND STUDY DESIGN: This
      study included 120 patients with GC, and the patients were classified into 3
      groups via random picking of envelopes: fiber-free nutrition formula (FF group, n
      = 40), fiber-enriched nutrition formula (FE group, n = 40), and fiber- and
      probiotic-enriched nutrition formula (FEP group, n = 40). All patients were given
      EN formulas for 7 consecutive days after surgery. RESULTS: The number of diarrhea
      cases was higher in the FF group than in the FE group (P = .007). The FEP group
      had a lower number of diarrhea cases compared with the FE group (P = .003).
      Patients in the FE group had a significantly shorter first flatus time than the
      FF group (P = .002). However, no significant difference was observed between the
      FE group and FEP group (P = .30). Intestinal disorders were similar between the
      FE group and FF group (P = .38). The FEP group had a lower number of intestinal
      disorder cases than the FF group (P = .03). LOHS in the FE and FEP groups was
      shorter than that in the FF group (P = .004; P < .001). However, no significant
      difference was observed between the FE and FEP groups (P = .28). In addition, no
      significant difference was observed between the 3 groups in terms of total
      lymphocyte count, albumin, prealbumin, and transferrin levels on day 7 of enteral
      feeding. CONCLUSIONS: The combination of fiber and probiotics was significantly
      effective in treating diarrhea that is associated with EN in postoperative
      patients with GC.

PMID- 29069043
TI  - The effect of preoperative administration of morphine in alleviating
      intraoperative pain of percutaneous transforaminal endoscopic discectomy under
      local anesthesia: A STROBE compliant study.
AB  - Local anesthesia is routinely recommended for percutaneous transforaminal
      endoscopic discectomy (PTED). However, the intense intraoperative pain remains a
      serious problem. The purpose of the current study is to find a safe and effective
      method to alleviate the intense pain during PTED for lumbar disc herniation (LDH)
      under local anesthesia.This study retrospectively analyzed 63 LDH patients who
      accepted PTED under local anesthesia. Thirty-one patients received intramuscular
      injection of morphine before PTED, while the other 32 were not. The 10 points
      visual analogue scale (VAS) was used to assess the patients' maximum leg and back
      pain. Patients were asked to grade their experiences of surgery and anesthesia on
      a 5-point Likert-type scale after the surgery. Modified Mac Nab Criteria were
      used to evaluate the surgical outcomes after 3-month follow-up.The intraoperative
      VAS scores of patients who accepted preoperative intervention decreased
      significantly. The postoperative VAS scores of both groups showed no
      significance. Patients who received preoperative intervention reported a higher
      subjective satisfaction rate with the surgery experience. According to the
      Modified Mac Nab criteria, the surgical outcomes of both groups were similar
      through the 3-month follow-up. After injection of morphine, 4 patients complained
      nausea and 2 patients experienced vomiting.Preoperative intramuscular injection
      of morphine could reduce the patients' pain during the PTED surgery and improve
      the patients' satisfaction without affecting the surgical outcome. Except for a
      higher incidence of nausea and vomiting, this method is relatively safe and
      convenient.

PMID- 29069044
TI  - Diagnostic value of the corrected QT difference between leads V1 and V6 in
      patients with acute pulmonary thromboembolism.
AB  - In acute pulmonary thromboembolism (PTE), right ventricular pressure overload
      impairs right-sided cardiac conduction and repolarization. We hypothesized that
      if heterogeneity of repolarization between right and left ventricles occurs in
      acute PTE, there would be the difference of repolarization between them.
      Therefore, we aimed to evaluate the diagnostic value of corrected QT interval
      (QTc) difference between leads V1 and V6 (V1 - V6) in patients with acute PTE.A
      total of 89 patients with suspected acute PTE who underwent computed tomographic
      angiography (CTA) were enrolled from January to December 2015. PTE was identified
      by CTA. We compared electrocardiographic (ECG) parameters, especially QTc
      difference (V1 - V6) between patients with PTE and those without PTE.Acute PTE
      was finally diagnosed in 45 patients. Clinical situations including the chief
      complaint were not different between PTE and non-PTE groups. S1Q3T3, a
      traditional ECG marker, had no diagnostic value for acute PTE. Patients with PTE
      had a significantly longer mean QTc in V1 (454.6 +/- 44.3 vs 417.5 +/- 31.3 ms, P
      < .001) and larger QTc difference (V1 - V6) (34.8 +/- 30.5 vs -12.5 +/- 16.6 ms,
      P < .001) than non-PTE controls. QTc difference (V1 - V6) was negative in all
      patients without PTE. PTE patients had a higher prevalence of T wave inversion in
      leads III (51.1% vs 29.5%, P = .038) and V1 (82.2% vs 38.6%, P < .001). A QTc
      difference (V1 - V6) of >=20 ms identified PTE with 82.2% sensitivity, 100.0%
      specificity, and 100.0% positive predictive value.QTc difference (V1 - V6) had an
      excellent diagnostic value for differentiating patients with and without acute
      PTE.

PMID- 29069045
TI  - Heart rate and outcomes in patients with heart failure with preserved ejection
      fraction: A dose-response meta-analysis.
AB  - Although elevated resting heart rate is related to poor outcomes in heart failure
      (HF) with reduced ejection fraction, the association in HF with preserved
      ejection fraction (HFpEF) remains inconclusive. Therefore, we conducted a dose
      response meta-analysis to examine the prognostic role of heart rate in patients
      with HFpEF.We searched PubMed and Embase databases until April 2017 and manually
      reviewed the reference lists of relevant literatures. Random effect models were
      used to pool the study-specific hazard ratio (HR) of outcomes, including all
      cause death, cardiovascular death, and HF hospitalization.Six studies with 7
      reports were finally included, totaling 14,054 patients with HFpEF. The summary
      HR (95% confidence interval [CI]) for every 10 beats/minute increment in heart
      rate was 1.04 (1.02-1.06) for all-cause death, 1.06 (1.02-1.10) for
      cardiovascular death, and 1.05 (1.01-1.08) for HF hospitalization. Subgroup
      analyses indicated that these positive relationships were significant in patients
      with sinus rhythm but not in those with atrial fibrillation. There was also
      evidence for nonlinear relationship of heart rate with each of the outcomes (All
      P for nonlinearity < .05).Higher heart rate in sinus rhythm is a risk factor for
      adverse outcomes in patients with HFpEF. Future trials are required to determine
      whether heart rate reduction may improve the prognosis of HFpEF.

PMID- 29069046
TI  - Analysis of three surgical treatments for spontaneous supratentorial
      intracerebral hemorrhage.
AB  - This retrospective study aimed to evaluate the effectiveness and safety of 3
      surgical procedures for Spontaneous Supratentorial Intracerebral Hemorrhage
      (SICH).A total of 63 patients with SICH were randomized into 3 groups. Group A (n
      = 21) underwent craniotomy surgery, group B (n = 22) underwent burr hole,
      urokinase infusion and catheter drainage, and group C (n = 20) underwent
      neuroendoscopic surgery. The hematoma evacuation rate of the operation was
      analyzed by 3D Slice software and the average surgery time, visualization during
      operation, decompressive effect, mortality, Glasgow Coma Scale (GCS) improvement,
      complications include rebleeding, pneumonia, intracranial infection were also
      compared among 3 groups.All procedures were successfully completed and the
      hematoma evacuation rate was significant differences among 3 groups which were
      79.8%, 43.1%, 89.3% respectively (P < .01), and group C was the highest group.
      Group B was smallest traumatic one and shared the shortest operation time, but
      for the lack of hemostasis, it also the highest rebleeding group (P = .03).
      Although there were different in complications, but there was no significant in
      pneumonia, intracranial infection, GCS improvement and mortality rate.All these 3
      methods had its own advantages and shortcomings, and every approach had its
      indications for SICH. Although for neuroendoscopic technical's minimal invasive,
      direct vision, effectively hematoma evacuation rate, and the relatively
      optimistic result, it might be a more promising approach for SICH.

PMID- 29069047
TI  - Amputation of the first metatarsophalangeal joint due to a giant gouty tophi: A
      case report.
AB  - RATIONALE: The first metatarsophalangeal joint (MTP1) is the most frequent site
      of gouty tophi. We report an unusual case with a giant skin-perforating tophi.
      This is the first case of gouty tophi at MTP1 which accepts surgical debulking
      and amputation. PATIENT CONCERNS: A 42-year-old man presented with a seven-year
      history of gout and a giant tophi at MTP1. The patient was referred to hospital
      due to persistent pain and ulcerations on the surface of the left MTP1. This
      rounded, giant, swelling, tophaceous tophi severely interfered with his normal
      walking. DIAGNOSES: The patient was diagnosed with gouty arthritis seven years
      ago, and did not receive regular anti-gout treatments. OUTCOMES: Biochemical
      examination showed he had raised serum uric acid (SUA, 11.92 mg/dl) and
      creatinine (258 MUmol/l). There was a severe joint destruction of MTP1 by X-ray
      examination. We controlled the skin infection by sulbenicillin. He was given
      febuxostat to reduce SUA. After 3 months of treatment, SUA fell to 6.8 mg/dl.
      Then we performed surgical debulking of MTP1 and amputation of hallux. Surgical
      operations obviously relieved the pain, and improved the function of his left
      foot. The visual closure after amputation was good. CONCLUSION: Surgical
      amputation of the gout lesion at MTP1 maximized the function, and reduced the
      pain of this patient. In the case of giant tophi with severe gouty arthritis or
      skin infections, surgical decisions need to weigh gains and losses carefully.

PMID- 29069050
TI  - Letters.

PMID- 29069052
TI  - Why attitudes matter in palliative care.

PMID- 29069049
TI  - Glucagonoma syndrome with serous oligocystic adenoma: A rare case report.
AB  - RATIONALE: Glucagonoma and pancreatic serous oligocystic adenoma (SOA) are rare
      neuroendocrine and exocrine tumors of the pancreas, respectively. The coexistence
      of glucagonoma syndrome (GS) and SOA is a rare clinical condition and has not yet
      been reported. Additionally, necrolytic migratory erythema (NME), a hallmark
      clinical sign of GS, is often misdiagnosed as other skin lesions by clinicians
      due to their lack of related knowledge, which delays diagnosis of GS and thus
      exacerbates the prognosis. PATIENT CONCERNS: A 50-year-old male patient was
      admitted to our department because he presented with diabetes mellitus and a
      recurrent ulcerated skin rash. Prior to the accurate diagnosis, the skin
      manifestation was considered to be diabetic dermopathy. DIAGNOSES: The patient's
      fasting serum glucagon level was up to 871.5 pg/mL. A biopsy of the pancreatic
      tumor revealed a pancreatic neuroendocrine tumor, and immunoperoxidase staining
      revealed glucagon-positive cells. In addition, the histological examination of
      the pancreatic cystic lesions showed typical features of SOA. INTERVENTIONS: The
      patient received a pancreaticoduodenal resection and radiofrequency ablation for
      the hepatic nodular lesion. OUTCOMES: One week after surgery, the glucagon
      concentration decreased to near normal levels. The cutaneous lesions
      spontaneously resolved within 4 weeks after surgery. LESSONS: Because almost all
      glucagonomas are malignant or have malignant potential, their early recognition
      and correct diagnosis are very important for a better prognosis, especially in
      cases with NME as the only manifestation during the development of glucagonomas.
      It is therefore imperative that clinicians recognize NME early to make an
      accurate diagnosis.

PMID- 29069048
TI  - Predictive factors associated with neck pain in patients with cervical disc
      degeneration: A cross-sectional study focusing on Modic changes.
AB  - The predictive factors associated with neck pain remain unclear. We conducted a
      cross-sectional study to assess predictive factors, especially Modic changes
      (MCs), associated with the intensity and duration of neck pain in patients with
      cervical disc degenerative disease.We retrospectively reviewed patients in our
      hospital from January 2013 to December 2016. Severe neck pain (SNP) and
      persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on
      the numerical rating scale (NRS). Basic data, and also imaging data, were
      collected and analyzed as potential predictive factors. Univariate analysis and
      multiple logistic regression analysis were performed to assess the predictive
      factors for neck pain.In all, 381 patients (193 males and 188 females) with
      cervical degenerative disease were included in our study. The number of patients
      with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck
      pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 +/
      0.9 vs 3.9 +/- 1.1; P = .004). The multivariate logistic analysis showed that
      kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044
      1.112), spondylolisthesis (OR 1.339, 95% CI 1.226-1.462), and annular tear (OR
      1.188, 95% CI 1.021-1.382) were factors associated with SNP, whereas kyphosis
      curvature (OR 1.568, 95% CI 1.022-2.394), spondylolisthesis (OR 1.486, 95% CI
      1.082-2.041), and MCs (OR 1.152, 95% CI 1.074-1.234) were associated with PNP.We
      concluded that kyphosis curvature, spondylolisthesis, and annular tear are
      associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are
      associated with PNP. This study supports the view that MCs can lead to a long
      duration of neck pain.

PMID- 29069054
TI  - How consistency in practice improved patient and staff satisfaction.

PMID- 29069059
TI  - The thunderstorm in room 12.

PMID- 29069055
TI  - Teach to think: Improving educators' perceived ability to teach critical
      thinking.

PMID- 29069060
TI  - Getting political about patient advocacy.

PMID- 29069061
TI  - Caring for our nation's veterans: A shared responsibility.

PMID- 29069062
TI  - Coping with grief during the holidays.

PMID- 29069064
TI  - Online resources for career development.

PMID- 29069063
TI  - Improving patient transitions from hospital to home: Practical advice from
      nurses.

PMID- 29069065
TI  - Cardiovascular drugs.

PMID- 29069066
TI  - Malaria: Still cause for concern.

PMID- 29069067
TI  - What's trigeminal neuralgia?

PMID- 29069068
TI  - Approaching ethical dilemmas with CARE.

PMID- 29069070
TI  - Calling on smartphones to enhance patient care.

PMID- 29069071
TI  - Clinical Significance of Routine Blood Test-Associated Inflammatory Index in
      Breast Cancer Patients.
AB  - BACKGROUND It is now widely acknowledged that chronic inflammation is closely
      associated with the process of cancer development. As a simple noninvasive blood
      based test, hematological parameters in the routine blood test have been
      considered as inflammation markers. We aimed to evaluate platelet count (PC), red
      blood cell distribution width (RDW), white blood cell count (WBC), mean platelet
      volume (MPV), number of neutrophils/lymphocytes ratio (NLR), and platelet
      count/lymphocytes ratio (PLR) as surrogate inflammatory markers in breast cancer
      (BC) patients, and we compared these to those in healthy individuals. MATERIAL
      AND METHODS A retrospective study was conducted in Zhongnan Hospital of Wuhan
      University from July 2014 to April 2015, including 110 cases of pathologically
      diagnosed BC patients and 78 cases of healthy females. Retrospective analysis of
      selected hematological parameters was performed between the 2 groups, as well as
      assessment of the correlation between these indexes and clinicopathological
      characteristics of the 110 breast cancer patients. RESULTS The mean values of
      RDW, MPV, NLR, and PLR were significantly higher in BC patients compared to the
      control group. The level of MPV exhibited positive correlations with lymph node
      metastasis and the Ki67 proliferation index in preoperative BC patients (P<0.05).
      Logistic regression analysis further showed that MPV was independently associated
      with the risk of BC lymph node metastasis (P<0.05). CONCLUSIONS Hematological
      parameters of RDW, MPV, NLR, and PLR can be used as an adjuvant tool for the
      diagnosis of BC. More importantly, the value of MPV can reflect the Ki67
      proliferation index before surgery and identify patients with positive lymph node
      metastasis.

PMID- 29069072
TI  - Non-union bone fracture: a quicker fix.

PMID- 29069073
TI  - Closing the gap.

PMID- 29069074
TI  - Noninvasive monitoring of brain edema after hypoxia in newborn piglets.
AB  - BackgroundDevelopment of cerebral edema after brain injury carries a high risk
      for brain damage and death. The present study tests the ability of a noninvasive
      cerebral edema monitoring system that uses near-infrared spectroscopy (NIRS) with
      water as the chromophore of interest to detect brain edema following
      hypoxia.MethodsVentilated piglets were exposed to hypoxia for 1 h, and then
      returned to normal oxygen levels for 4 h. An NIRS sensor was placed on the
      animal's head at baseline, and changes in light attenuation were converted to
      changes in H2O. Cerebral water content and aquaporin-4 protein (AQP4) expression
      were measured.ResultsThe system detected changes in NIRS-derived water signal as
      early as 2 h after hypoxia, and provided fivefold signal amplification,
      representing a 10% increase in brain water content and a sixfold increase in
      AQP4, 4 h after hypoxia. Changes in water signal correlated well with changes in
      cerebral water content (R=0.74) and AQP4 expression (R=0.97) in the piglet
      brain.ConclusionThe data show that NIRS can detect cerebral edema early in the
      injury process, thus providing an opportunity to initiate therapy at an earlier
      and more effective time-point after an insult than is available with current
      technology.

PMID- 29069075
TI  - Research in the sciences of improvement, implementation, and pediatric patient
      safety.

PMID- 29069076
TI  - Childhood stunting in relation to the pre- and postnatal environment during the
      first 2 years of life: The MAL-ED longitudinal birth cohort study.
AB  - BACKGROUND: Stunting is the most prevalent manifestation of childhood
      malnutrition. To characterize factors that contribute to stunting in resource
      poor settings, we studied a priori selected biological and social factors
      collected longitudinally in a cohort of newborns. METHODS AND FINDINGS: We
      enrolled 1,868 children across 7 resource-poor settings in Bangladesh, Brazil,
      India, Nepal, Peru, South Africa, and Tanzania shortly after birth and followed
      them for 24 months between 2 November 2009 and 28 February 2014. We collected
      longitudinal anthropometry, sociodemographic factors, maternal-reported
      illnesses, and antibiotic use; child feeding practices; dietary intake starting
      at 9 months; and longitudinal blood, urine, and stool samples to investigate non
      diarrheal enteropathogens, micronutrients, gut inflammation and permeability, and
      systemic inflammation. We categorized length-for-age Z-scores into 3 groups (not
      stunted, >=-1; at risk, <-1 to -2; and stunted, <-2), and used multivariable
      ordinal logistic regression to model the cumulative odds of being in a lower
      length-for-age category (at risk or stunted). A total of 1,197 children with
      complete longitudinal data were available for analysis. The prevalence of having
      a length-for-age Z-score below -1 increased from 43% (range 37%-47% across sites)
      shortly after birth (mean 7.7 days post-delivery, range 0 to 17 days) to 74% (16%
      96%) at 24 months. The prevalence of stunting increased 3-fold during this same
      time period. Factors that contributed to the odds of being in a lower length-for
      age category at 24 months were lower enrollment weight-for-age (interquartile
      cumulative odds ratio = 1.82, 95% CI 1.49-2.23), shorter maternal height (2.38,
      1.89-3.01), higher number of enteropathogens in non-diarrheal stools (1.36, 1.07
      1.73), lower socioeconomic status (1.75, 1.20-2.55), and lower percent of energy
      from protein (1.39, 1.13-1.72). Site-specific analyses suggest that reported
      associations were similar across settings. While loss to follow-up and missing
      data are inevitable, some study sites had greater loss to follow-up and more
      missing data than others, which may limit the generalizability of the findings.
      CONCLUSIONS: Neonatal and maternal factors were early determinants of lower
      length-for-age, and their contribution remained important throughout the first 24
      months of life, whereas the average number of enteropathogens in non-diarrheal
      stools, socioeconomic status, and dietary intake became increasingly important
      contributors by 24 months relative to neonatal and maternal factors.

PMID- 29069077
TI  - Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in
      intellectual disability and autism spectrum disorder.
AB  - Kleefstra syndrome, caused by haploinsufficiency of euchromatin histone
      methyltransferase 1 (EHMT1), is characterized by intellectual disability (ID),
      autism spectrum disorder (ASD), characteristic facial dysmorphisms, and other
      variable clinical features. In addition to EHMT1 mutations, de novo variants were
      reported in four additional genes (MBD5, SMARCB1, NR1I3, and KMT2C), in single
      individuals with clinical characteristics overlapping Kleefstra syndrome. Here,
      we present a novel cohort of five patients with de novo loss of function
      mutations affecting the histone methyltransferase KMT2C. Our clinical data
      delineates the KMT2C phenotypic spectrum and reinforces the phenotypic overlap
      with Kleefstra syndrome and other related ID disorders. To elucidate the common
      molecular basis of the neuropathology associated with mutations in KMT2C and
      EHMT1, we characterized the role of the Drosophila KMT2C ortholog, trithorax
      related (trr), in the nervous system. Similar to the Drosophila EHMT1 ortholog,
      G9a, trr is required in the mushroom body for short term memory. Trr ChIP-seq
      identified 3371 binding sites, mainly in the promoter of genes involved in
      neuronal processes. Transcriptional profiling of pan-neuronal trr knockdown and
      G9a null mutant fly heads identified 613 and 1123 misregulated genes,
      respectively. These gene sets show a significant overlap and are associated with
      nearly identical gene ontology enrichments. The majority of the observed
      biological convergence is derived from predicted indirect target genes. However,
      trr and G9a also have common direct targets, including the Drosophila ortholog of
      Arc (Arc1), a key regulator of synaptic plasticity. Our data highlight the
      clinical and molecular convergence between the KMT2 and EHMT protein families,
      which may contribute to a molecular network underlying a larger group of ID/ASD
      related disorders.

PMID- 29069078
TI  - Transcriptomic correlates of neuron electrophysiological diversity.
AB  - How neuronal diversity emerges from complex patterns of gene expression remains
      poorly understood. Here we present an approach to understand electrophysiological
      diversity through gene expression by integrating pooled- and single-cell
      transcriptomics with intracellular electrophysiology. Using neuroinformatics
      methods, we compiled a brain-wide dataset of 34 neuron types with paired gene
      expression and intrinsic electrophysiological features from publically accessible
      sources, the largest such collection to date. We identified 420 genes whose
      expression levels significantly correlated with variability in one or more of 11
      physiological parameters. We next trained statistical models to infer cellular
      features from multivariate gene expression patterns. Such models were predictive
      of gene-electrophysiological relationships in an independent collection of 12
      visual cortex cell types from the Allen Institute, suggesting that these
      correlations might reflect general principles relating expression patterns to
      phenotypic diversity across very different cell types. Many associations reported
      here have the potential to provide new insights into how neurons generate
      functional diversity, and correlations of ion channel genes like Gabrd and Scn1a
      (Nav1.1) with resting potential and spiking frequency are consistent with known
      causal mechanisms. Our work highlights the promise and inherent challenges in
      using cell type-specific transcriptomics to understand the mechanistic origins of
      neuronal diversity.

PMID- 29069079
TI  - Conservation of reef manta rays (Manta alfredi) in a UNESCO World Heritage Site:
      Large-scale island development or sustainable tourism?
AB  - A large reef manta ray (Manta alfredi) aggregation has been observed off the
      north Sudanese Red Sea coast since the 1950s. Sightings have been predominantly
      within the boundaries of a marine protected area (MPA), which was designated a
      UNESCO World Heritage Site in July 2016. Contrasting economic development
      trajectories have been proposed for the area (small-scale ecotourism and large
      scale island development). To examine space-use, Wildlife Computers(r) SPOT 5
      tags were secured to three manta rays. A two-state switching Bayesian state space
      model (BSSM), that allowed movement parameters to switch between resident and
      travelling, was fit to the recorded locations, and 50% and 95% kernel utilization
      distributions (KUD) home ranges calculated. A total of 682 BSSM locations were
      recorded between 30 October 2012 and 6 November 2013. Of these, 98.5% fell within
      the MPA boundaries; 99.5% for manta 1, 91.5% for manta 2, and 100% for manta 3.
      The BSSM identified that all three mantas were resident during 99% of
      transmissions, with 50% and 95% KUD home ranges falling mainly within the MPA
      boundaries. For all three mantas combined (88.4%), and all individuals (manta 1
      92.4%, manta 2-64.9%, manta 3-91.9%), the majority of locations occurred within
      15 km of the proposed large-scale island development. Results indicated that the
      MPA boundaries are spatially appropriate for manta rays in the region, however, a
      close association to the proposed large-scale development highlights the
      potential threat of disruption. Conversely, the focused nature of spatial use
      highlights the potential for reliable ecotourism opportunities.

PMID- 29069080
TI  - Un-gating and allosteric modulation of a pentameric ligand-gated ion channel
      captured by molecular dynamics.
AB  - Pentameric ligand-gated ion channels (pLGICs) mediate intercellular communication
      at synapses through the opening of an ion pore in response to the binding of a
      neurotransmitter. Despite the increasing availability of high-resolution
      structures of pLGICs, a detailed understanding of the functional isomerization
      from closed to open (gating) and back is currently missing. Here, we provide the
      first atomistic description of the transition from open to closed (un-gating) in
      the glutamate-gated chloride channel (GluCl) from Caenorhabditis Elegans.
      Starting with the active-state structure solved in complex with the
      neurotransmitter L-glutamate and the positive allosteric modulator (PAM)
      ivermectin, we analyze the spontaneous relaxation of the channel upon removal of
      ivermectin by explicit solvent/membrane Molecular Dynamics (MD) simulations. The
      MUs-long trajectories support the conclusion that ion-channel deactivation is
      mediated by two distinct quaternary transitions, i.e. a global receptor twisting
      followed by the radial expansion (or blooming) of the extracellular domain. At
      variance with previous models, we show that pore closing is exclusively regulated
      by the global twisting, which controls the position of the beta1-beta2 loop
      relative to the M2-M3 loop at the EC/TM domain interface. Additional simulations
      with L-glutamate restrained to the crystallographic binding mode and ivermectin
      removed indicate that the same twisting isomerization is regulated by agonist
      binding at the orthosteric site. These results provide a structural model for
      gating in pLGICs and suggest a plausible mechanism for the pharmacological action
      of PAMs in this neurotransmitter receptor family. The simulated un-gating
      converges to the X-ray structure of GluCl resting state both globally and
      locally, demonstrating the predictive character of state-of-art MD simulations.

PMID- 29069082
TI  - Discovery of the first ichthyosaur from the Jurassic of India: Implications for
      Gondwanan palaeobiogeography.
AB  - An articulated and partially preserved skeleton of an ichthyosaur was found in
      the Upper Jurassic (Upper Kimmeridgian) Katrol Formation exposed at a site south
      of the village Lodai in Kachchh district, Gujarat (western India). Here we
      present a detailed description and inferred taxonomic relationship of the
      specimen. The present study revealed that the articulated skeleton belongs to the
      family Ophthalmosauridae. The new discovery from India further improves the
      depauperate fossil record of ichthyosaurs from the former Gondwanan continents.
      Based on the preserved length of the axial skeleton and anterior part of the
      snout and taking into account the missing parts of the skull and postflexural
      region, it is suggested that the specimen may represent an adult possibly
      reaching a length of 5.0-5.5 m. The widespread occurrence of ophthalmosaurids in
      the Upper Jurassic deposits of western Tethys, Madagascar, South America and
      India points to possible faunal exchanges between the western Tethys and
      Gondwanan continents through a southern seaway.

PMID- 29069081
TI  - Spatiotemporal changes in the distribution of LHFPL5 in mice cochlear hair
      bundles during development and in the absence of PCDH15.
AB  - Mechanosensory transduction by vertebrate hair cells depends on a protein complex
      at the tips of shorter stereocilia associated with mechanoelectrical transduction
      channels activated by tip links in the hair bundle. In mammalian hair cells, this
      complex includes transmembrane channel-like protein subunit 1 (TMC1), lipoma
      HMGIC fusion partner-like 5 protein (LHFPL5) and protocadherin 15 (PCDH15), a
      lower-end component of the tip link. TMC1 interacts with LHFPL5 and PCDH15 but
      how the complex develops to maturity, and the relationships between these
      proteins, remains uncertain. Here we evaluate the spatiotemporal development of
      LHFPL5 distributions in mouse cochlear hair bundles by immunofluorescence and
      immunogold transmission electron microscopy, from postnatal day 0 (P0) through
      P21 in wild type and PCDH15-deficient mice. At P0, hair bundles contain many
      short microvilli-like processes which we term unranked stereocilia, and a subset
      of lengthening rows, adjacent to a kinocilium. LHFPL5 is distributed throughout
      the bundle, including on stereocilia tips and the kinocilium. At P3, 4-to-6 rows
      of ranked stereocilia are evident, total LHFPL5 expression peaks, and LHFPL5 is
      localised to ranked stereocilia tips of all rows and to lower shaft/ankle links.
      By P12, the bundle has a mature pattern with 3 ranked rows but virtually no
      unranked stereocilia or kinocilium; LHFPL5 expression has declined and become
      restricted to the tips of shorter stereocilia. Throughout development from P0,
      expression of LHFPL5 is greater overall on apical than basal bundles, but there
      is, on average, an equal amount of labelling per labelled tip. In P3 mice lacking
      PCDH15, LHFPL5 labelling is not at the tips but is primarily on unranked
      stereocilia and lower lateral links. These data show that LHFPL5 is already
      present in the MET apparatus at P0 but requires PCDH15 at P3 to remain there.
      Shaft/ankle link localisation suggests it interacts with link proteins other than
      PCDH15.

PMID- 29069083
TI  - RhoGEF9 splice isoforms influence neuronal maturation and synapse formation
      downstream of alpha2 GABAA receptors.
AB  - In developing brain neuronal migration, dendrite outgrowth and dendritic spine
      outgrowth are controlled by Cdc42, a small GTPase of the Rho family, and its
      activators. Cdc42 function in promoting actin polymerization is crucial for
      glutamatergic synapse regulation. Here, we focus on GABAergic synapse-specific
      activator of Cdc42, collybistin (CB) and examine functional differences between
      its splice isoforms CB1 and CB2. We report that CB1 and CB2 differentially
      regulate GABAergic synapse formation in vitro along proximal-distal axis and
      adult-born neuron maturation in vivo. The functional specialization between CB1
      and CB2 isoforms arises from their differential protein half-life, in turn
      regulated by ubiquitin conjugation of the unique CB1 C-terminus. We report that
      CB1 and CB2 negatively regulate Cdc42; however, Cdc42 activation is dependent on
      CB interaction with gephyrin. During hippocampal adult neurogenesis CB1 regulates
      neuronal migration, while CB2 is essential for dendrite outgrowth. Finally, using
      mice lacking Gabra2 subunit, we show that CB1 function is downstream of GABAARs,
      and we can rescue adult neurogenesis deficit observed in Gabra2 KO. Overall, our
      results uncover previously unexpected role for CB isoforms downstream of alpha2
      containing GABAARs during neuron maturation in a Cdc42 dependent mechanism.

PMID- 29069085
TI  - Influence of pharmaceutical marketing on Medicare prescriptions in the District
      of Columbia.
AB  - IMPORTANCE: Gifts from pharmaceutical companies are believed to influence
      prescribing behavior, but few studies have addressed the association between
      industry gifts to physicians and drug costs, prescription volume, or preference
      for generic drugs. Even less research addresses the effect of gifts on the
      prescribing behavior of nurse practitioners (NPs), physician assistants (PAs),
      and podiatrists. OBJECTIVE: To analyze the association between gifts provided by
      pharmaceutical companies to individual prescribers in Washington DC and the
      number of prescriptions, cost of prescriptions, and proportion of branded
      prescriptions for each prescriber. DESIGN: Gifts data from the District of
      Columbia's (DC) AccessRx program and the federal Center for Medicare and Medicaid
      Services (CMS) Open Payments program were analyzed with claims data from the CMS
      2013 Medicare Provider Utilization and Payment Data. SETTING: Washington DC,
      2013. PARTICIPANTS: Physicians, nurse practitioners, physician assistants,
      podiatrists, and other licensed Medicare Part D prescribers who participated in
      Medicare Part D (a Federal prescription drug program that covers patients over
      age 65 or who are disabled). EXPOSURE(S): Gifts to healthcare prescribers
      (including cash, meals, and ownership interests) from pharmaceutical companies.
      MAIN OUTCOMES AND MEASURES: Average number of Medicare Part D claims per
      prescriber, number of claims per patient, cost per claim, and proportion of
      branded claims. RESULTS: In 2013, 1,122 (39.1%) of 2,873 Medicare Part D
      prescribers received gifts from pharmaceutical companies totaling $3.9 million in
      2013. Compared to non-gift recipients, gift recipients prescribed 2.3 more claims
      per patient, prescribed medications costing $50 more per claim, and prescribed
      7.8% more branded drugs. In six specialties (General Internal Medicine, Family
      Medicine, Obstetrics/Gynecology, Urology, Ophthalmology, and Dermatology), gifts
      were associated with a significantly increased average cost of claims. For
      Internal Medicine, Family Medicine, and Ophthalmology, gifts were associated with
      more branded claims. Gift acceptance was associated with increased average cost
      per claim for PAs and NPs. Gift acceptance was also associated with higher
      proportion of branded claims for PAs but not NPs. Physicians who received small
      gifts (less than $500 annually) had more expensive claims ($114 vs. $85) and more
      branded claims (30.3% vs. 25.7%) than physicians who received no gifts. Those
      receiving large gifts (greater than $500 annually) had the highest average costs
      per claim ($189) and branded claims (39.9%) than other groups. All differences
      were statistically significant (p<0.05). CONCLUSIONS AND RELEVANCE: Gifts from
      pharmaceutical companies are associated with more prescriptions per patient, more
      costly prescriptions, and a higher proportion of branded prescriptions with
      variation across specialties. Gifts of any size had an effect and larger gifts
      elicited a larger impact on prescribing behaviors. Our study confirms and expands
      on previous work showing that industry gifts are associated with more expensive
      prescriptions and more branded prescriptions. Industry gifts influence
      prescribing behavior, may have adverse public health implications, and should be
      banned.

PMID- 29069084
TI  - Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA
      stability in Saccharomyces cerevisiae.
AB  - Heterochromatin contains a significant part of nuclear DNA. Little is known about
      the mechanisms that govern heterochromatic DNA stability. We show here that in
      the yeast Saccharomyces cerevisiae (i) DNA mismatch repair (MMR) is required for
      the maintenance of heterochromatic DNA stability, (ii) MutLalpha (Mlh1-Pms1
      heterodimer), MutSalpha (Msh2-Msh6 heterodimer), MutSbeta (Msh2-Msh3
      heterodimer), and Exo1 are involved in MMR at heterochromatin, (iii) Exo1
      independent MMR at heterochromatin frequently leads to the formation of Pol zeta
      dependent mutations, (iv) MMR cooperates with the proofreading activity of Pol
      epsilon and the histone acetyltransferase Rtt109 in the maintenance of
      heterochromatic DNA stability, (v) repair of base-base mismatches at
      heterochromatin is less efficient than repair of base-base mismatches at
      euchromatin, and (vi) the efficiency of repair of 1-nt insertion/deletion loops
      at heterochromatin is similar to the efficiency of repair of 1-nt
      insertion/deletion loops at euchromatin.

PMID- 29069086
TI  - Rnr1, but not Rnr3, facilitates the sustained telomerase-dependent elongation of
      telomeres.
AB  - Ribonucleotide reductase (RNR) provides the precursors for the generation of
      dNTPs, which are required for DNA synthesis and repair. Here, we investigated the
      function of the major RNR subunits Rnr1 and Rnr3 in telomere elongation in
      budding yeast. We show that Rnr1 is essential for the sustained elongation of
      short telomeres by telomerase. In the absence of Rnr1, cells harbor very short,
      but functional, telomeres, which cannot become elongated by increased telomerase
      activity or by tethering of telomerase to telomeres. Furthermore, we demonstrate
      that Rnr1 function is critical to prevent an early onset of replicative
      senescence and premature survivor formation in telomerase-negative cells but
      dispensable for telomere elongation by Homology-Directed-Repair. Our results
      suggest that telomerase has a "basal activity" mode that is sufficient to
      compensate for the "end-replication-problem" and does not require the presence of
      Rnr1 and a different "sustained activity" mode necessary for the elongation of
      short telomeres, which requires an upregulation of dNTP levels and dGTP ratios
      specifically through Rnr1 function. By analyzing telomere length and dNTP levels
      in different mutants showing changes in RNR complex composition and activity we
      provide evidence that the Mec1ATR checkpoint protein promotes telomere elongation
      by increasing both dNTP levels and dGTP ratios through Rnr1 upregulation in a
      mechanism that cannot be replaced by its homolog Rnr3.

PMID- 29069087
TI  - Values in environmental research: Citizens' views of scientists who acknowledge
      values.
AB  - Scientists who perform environmental research on policy-relevant topics face
      challenges when communicating about how values may have influenced their
      research. This study examines how citizens view scientists who publicly
      acknowledge values. Specifically, we investigate whether it matters: if citizens
      share or oppose a scientist's values, if a scientist's conclusions seem contrary
      to or consistent with the scientist's values, and if a scientist is assessing the
      state of the science or making a policy recommendation. We conducted two 3x2
      factorial design online experiments. Experiment 1 featured a hypothetical
      scientist assessing the state of the science on the public-health effects of
      exposure to Bisphenol A (BPA), and Experiment 2 featured a scientist making a
      policy recommendation on use of BPA. We manipulated whether or not the scientist
      expressed values and whether the scientist's conclusion appeared contrary to or
      consistent with the scientist's values, and we accounted for whether or not
      subjects' values aligned with the scientist's values. We analyzed our data with
      ordinary least squares (OLS) regression techniques. Our results provide at least
      preliminary evidence that acknowledging values may reduce the perceived
      credibility of scientists within the general public, but this effect differs
      depending on whether scientists and citizens share values, whether scientists
      draw conclusions that run contrary to their values, and whether scientists make
      policy recommendations.

PMID- 29069088
TI  - Donation of peripheral blood stem cells to unrelated strangers: A thematic
      analysis.
AB  - BACKGROUND: Donation of haematopoietic stem cells, either through bone marrow
      (BM) or peripheral blood stem cell (PBSC) collection, is a generally safe
      procedure for healthy donors, although side effects are a known risk. Previous
      research, including our recent quantitative study, has shown that the
      psychosocial response to donating is usually a positive one and most donors would
      be willing to donate again in the future. This is often despite experiencing
      significant side effects during the donation process. Due to the relative recent
      introduction of PBSC, a comprehensive understanding of the range of physical and
      emotional issues donors may experience is lacking, as well as an understanding of
      specific donor characteristics Qualitative research can provide rich narrative
      data into these areas. This study was set up in order to identify specific donor
      characteristics and to further explore the relationship between pre-donation
      physical health and the donation experience, as previously identified in our
      quantitative study. METHODS: It involved in-depth telephone interviews with 14
      PBSC donors who participated in our original quantitative study. Thematic
      analysis was used to analyse the findings and the results provide a summary of
      participants' characteristics using themes and constituent codes. RESULTS: We
      identified several donor characteristics, including strong intrinsic motivation,
      altruism, sense of duty, determination, low levels of ambivalence and the ability
      to develop a strong emotional relationship with an (unknown/anonymous) recipient
      whilst being able to manage strong feelings and emotions. CONCLUSIONS: These
      personality traits may explain the resilience that has been observed previously
      in haematopoietic stem cells donors. Significant feelings of grief were reported
      after a recipient's death. Possibilities to alleviate these symptoms may include
      raising awareness of potential poor outcomes in the recipient and offering
      improved counselling services if the recipient dies. We acknowledge several
      limitations including the sampling frame.

PMID- 29069090
TI  - The MELD-Plus: A generalizable prediction risk score in cirrhosis.
AB  - BACKGROUND AND AIMS: Accurate assessment of the risk of mortality following a
      cirrhosis-related admission can enable health-care providers to identify high
      risk patients and modify treatment plans to decrease the risk of mortality.
      METHODS: We developed a post-discharge mortality prediction model for patients
      with a cirrhosis-related admission using a population of 314,292 patients who
      received care either at Massachusetts General Hospital (MGH) or Brigham and
      Women's Hospital (BWH) between 1992 and 2010. We extracted 68 variables from the
      electronic medical records (EMRs), including demographics, laboratory values,
      diagnosis codes, and medications. We then used a regularized logistic regression
      to select the most informative variables and created a risk score that comprises
      the selected variables. To evaluate the potential for generalizability of our
      score, we applied it on all cirrhosis-related admissions between 2010 and 2015 at
      an independent EMR data source of more than 18 million patients, pooled from
      different health-care systems with EMRs. We calculated the areas under the
      receiver operating characteristic curves (AUROCs) to assess prediction
      performance. RESULTS: We identified 4,781 cirrhosis-related admissions at MGH/BWH
      hospitals, of which 778 resulted in death within 90 days of discharge. Nine
      variables were the most effective predictors for 90-day mortality, and these
      included all MELD-Na's components, as well as albumin, total cholesterol, white
      blood cell count, age, and length of stay. Applying our nine-variable risk score
      (denoted as "MELD-Plus") resulted in an improvement over MELD and MELD-Na scores
      in several prediction models. On the MGH/BWH 90-day model, MELD-Plus improved the
      performance of MELD-Na by 11.4% (0.78 [95% CI, 0.75-0.81] versus 0.70 [95% CI,
      0.66-0.73]). In the MGH/BWH approximate 1-year model, MELD-Plus improved the
      performance of MELD-Na by 8.3% (0.78 [95% CI, 0.76-0.79] versus 0.72 [95% CI,
      0.71-0.73]). Performance improvement was similar when the novel MELD-Plus risk
      score was applied to an independent database; when considering 24,042 cirrhosis
      related admissions, MELD-Plus improved the performance of MELD-Na by 16.9% (0.69
      [95% CI, 0.69-0.70] versus 0.59 [95% CI, 0.58-0.60]). CONCLUSIONS: We developed a
      new risk score, MELD-Plus that accurately stratifies the short-term mortality of
      patients with established cirrhosis, following a hospital admission. Our findings
      demonstrate that using a small set of easily accessible structured variables can
      help identify novel predictors of outcomes in cirrhosis patients and improve the
      performance of widely used traditional risk scores.

PMID- 29069091
TI  - Childhood socioeconomic position and adult mental wellbeing: Evidence from four
      British birth cohort studies.
AB  - BACKGROUND: There is much evidence showing that childhood socioeconomic position
      is associated with physical health in adulthood; however existing evidence on how
      early life disadvantage is associated with adult mental wellbeing is
      inconsistent. This paper investigated whether childhood socioeconomic position
      (SEP) is associated with adult mental wellbeing and to what extent any
      association is explained by adult SEP using harmonised data from four British
      birth cohort studies. METHODS: The sample comprised 20,717 participants with
      mental wellbeing data in the Hertfordshire Cohort Study (HCS), the MRC National
      Survey of Health and Development (NSHD), the National Child Development Study
      (NCDS), and the British Cohort Study (BCS70). Warwick Edinburgh Mental Wellbeing
      Scale (WEMWBS) scores at age 73 (HCS), 60-64 (NSHD), 50 (NCDS), or 42 (BCS70)
      were used. Harmonised socioeconomic position (Registrar General's Social
      Classification) was ascertained in childhood (age 10/11) and adulthood (age
      42/43). Associations between childhood SEP, adult SEP, and wellbeing were tested
      using linear regression and multi-group structural equation models. RESULTS: More
      advantaged father's social class was associated with better adult mental
      wellbeing in the BCS70 and the NCDS. This association was independent of adult
      SEP in the BCS70 but fully mediated by adult SEP in the NCDS. There was no
      evidence of an association between father's social class and adult mental
      wellbeing in the HCS or the NSHD. CONCLUSIONS: Socioeconomic conditions in
      childhood are directly and indirectly, through adult socioeconomic pathways,
      associated with adult mental wellbeing, but findings from these harmonised data
      suggest this association may depend on cohort or age.

PMID- 29069092
TI  - The sense of hearing in the Pacific oyster, Magallana gigas.
AB  - There is an increasing concern that anthropogenic noise could have a significant
      impact on the marine environment, but there is still insufficient data for most
      invertebrates. What do they perceive? We investigated this question in oysters
      Magallana gigas (Crassostrea gigas) using pure tone exposures, accelerometer
      fixed on the oyster shell and hydrophone in the water column. Groups of 16
      oysters were exposed to quantifiable waterborne sinusoidal sounds in the range of
      10 Hz to 20 kHz at various acoustic energies. The experiment was conducted in
      running seawater using an experimental flume equipped with suspended
      loudspeakers. The sensitivity of the oysters was measured by recording their
      valve movements by high-frequency noninvasive valvometry. The tests were 3 min
      tone exposures including a 70 sec fade-in period. Three endpoints were analysed:
      the ratio of responding individuals in the group, the resulting changes of valve
      opening amplitude and the response latency. At high enough acoustic energy,
      oysters transiently closed their valves in response to frequencies in the range
      of 10 to <1000 Hz, with maximum sensitivity from 10 to 200 Hz. The minimum
      acoustic energy required to elicit a response was 0.02 m?s-2 at 122 dBrms re 1
      MUPa for frequencies ranging from 10 to 80 Hz. As a partial valve closure cannot
      be differentiated from a nociceptive response, it is very likely that oysters
      detect sounds at lower acoustic energy. The mechanism involved in sound detection
      and the ecological consequences are discussed.

PMID- 29069089
TI  - An alpha-Gal-containing neoglycoprotein-based vaccine partially protects against
      murine cutaneous leishmaniasis caused by Leishmania major.
AB  - BACKGROUND: Protozoan parasites from the genus Leishmania cause broad clinical
      manifestations known as leishmaniases, which affect millions of people worldwide.
      Cutaneous leishmaniasis (CL), caused by L. major, is one the most common forms of
      the disease in the Old World. There is no preventive or therapeutic human vaccine
      available for L. major CL, and existing drug treatments are expensive, have toxic
      side effects, and resistant parasite strains have been reported. Hence, further
      therapeutic interventions against the disease are necessary. Terminal, non
      reducing, and linear alpha-galactopyranosyl (alpha-Gal) epitopes are abundantly
      found on the plasma membrane glycolipids of L. major known as
      glycoinositolphospholipids. The absence of these alpha-Gal epitopes in human
      cells makes these glycans highly immunogenic and thus potential targets for
      vaccine development against CL. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      evaluated three neoglycoproteins (NGPs), containing synthetic alpha-Gal epitopes
      covalently attached to bovine serum albumin (BSA), as vaccine candidates against
      L. major, using alpha1,3-galactosyltransferase-knockout (alpha1,3GalT-KO) mice.
      These transgenic mice, similarly to humans, do not express nonreducing, linear
      alpha-Gal epitopes in their cells and are, therefore, capable of producing high
      levels of anti-alpha-Gal antibodies. We observed that Galalpha(1,6)Galbeta-BSA
      (NGP5B), but not Galalpha(1,4)Galbeta-BSA (NGP12B) or Galalpha(1,3)Galalpha-BSA
      (NGP17B), was able to significantly reduce the size of footpad lesions by 96% in
      comparison to control groups. Furthermore, we observed a robust humoral and
      cellular immune response with production of high levels of protective lytic anti
      alpha-Gal antibodies and induction of Th1 cytokines. CONCLUSIONS/SIGNIFICANCE: We
      propose that NGP5B is an attractive candidate for the study of potential
      synthetic alpha-Gal-neoglycoprotein-based vaccines against L. major infection.

PMID- 29069093
TI  - The first megatheropod tracks from the Lower Jurassic upper Elliot Formation,
      Karoo Basin, Lesotho.
AB  - A palaeosurface with one megatheropod trackway and several theropod tracks and
      trackways from the Lower Jurassic upper Elliot Formation (Stormberg Group, Karoo
      Supergroup) in western Lesotho is described. The majority of the theropod tracks
      are referable to either Eubrontes or Kayentapus based on their morphological
      characteristics. The larger megatheropod tracks are 57 cm long and have no
      Southern Hemisphere equivalent. Morphologically, they are more similar to the
      Early Jurassic Kayentapus, as well as the much younger Upper Cretaceous
      ichnogenus Irenesauripus, than to other contemporaneous ichnogenera in southern
      Africa. Herein they have been placed within the ichnogenus Kayentapus and
      described as a new ichnospecies (Kayentapus ambrokholohali). The tracks are
      preserved on ripple marked, very fine-grained sandstone of the Lower Jurassic
      upper Elliot Formation, and thus were made after the end-Triassic mass extinction
      event (ETE). This new megatheropod trackway site marks the first occurrence of
      very large carnivorous dinosaurs (estimated body length >8-9 meters) in the Early
      Jurassic of southern Gondwana, an evolutionary strategy that was repeatedly
      pursued and amplified in the following ~135 million years, until the next major
      biotic crisis at the end-Cretaceous.

PMID- 29069094
TI  - The oldest record of Alvarezsauridae (Dinosauria: Theropoda) in the Northern
      Hemisphere.
AB  - Procoelous caudal vertebrae, a carpometacarpus with a hypertrophied metacarpal
      II, and robust proximal and ungual phalanges of manual digit II of a small
      theropod dinosaur from the Upper Cretaceous (Turonian) Bissekty Formation at
      Dzharakuduk, Uzbekistan, show unequivocal synapomorphies of the clade
      Alvarezsauridae and thus are referred to it. The caudal vertebrae have a unique
      longitudinal canal within the neural arch. The carpometacarpus, with metacarpal
      III occupying about one third of the width of the carpometacarpus, shows the most
      plesiomorphic stage of the evolution of the forelimb among known alvarezsaurids.
      The proximal phalanx of manual digit II differs from the corresponding bone in
      Parvicursorinae in having a less asymmetrical proximal articular surface without
      a dorsal process and short ventral ridges. The ungual phalanx of manual digit II
      has laterally open ventral foramina. The Bissekty alvarezsaurid possibly
      represents a basal parvicursorine and is the stratigraphically oldest known
      alvarezsaurid in Asia known to date.

PMID- 29069095
TI  - Hypothyroidism as a risk factor for open angle glaucoma: A systematic review and
      meta-analysis.
AB  - PURPOSE: The relationship between hypothyroidism and primary open angle glaucoma
      (POAG) has attracted intense interest recently, but the reported results have
      been controversial. This meta-analysis was carried out to determine the
      association between hypothyroidism and POAG. METHODS: The literature was
      identified from three databases (Web of Science, Embase, and PubMed). The meta
      analyses were performed using random-effects models, with results reported as
      adjusted odds ratios (ORs) with 95% confidence intervals (CI 95%). RESULTS: A
      total of 11 studies meeting the inclusion criteria were included in the final
      meta-analysis. The pooled OR based on 11 risk estimates showed a statistically
      significant increased risk of POAG prevalence among individuals with
      hypothyroidism (OR = 1.64, 95% CI = 1.27-2.13). Substantial heterogeneity among
      these studies was detected (P < 0.001; I2 = 83.2%). Sub-group analysis revealed
      that the cohort studies and case-control studies showed a significant association
      between hypothyroidism and POAG, which was not observed in cross-sectional
      studies. There was no significant publication bias in this study. CONCLUSIONS:
      The findings of this meta-analysis indicate that individuals with hypothyroidism
      have an increased risk of developing POAG.

PMID- 29069096
TI  - Community assembly of coral reef fishes along the Melanesian biodiversity
      gradient.
AB  - The Indo-Pacific is home to Earth's most biodiverse coral reefs. Diversity on
      these reefs decreases from the Coral Triangle east through the islands of
      Melanesia. Despite this pattern having been identified during the early 20th
      century, our knowledge about the interaction between pattern and process remains
      incomplete. To evaluate the structure of coral reef fish communities across
      Melanesia, we obtained distributional records for 396 reef fish species in five
      taxa across seven countries. We used hierarchical clustering, nestedness, and
      multiple linear regression analyses to evaluate the community structure. We also
      compiled data on life history traits (pelagic larval duration, body size and
      schooling behavior) to help elucidate the ecological mechanisms behind community
      structure. Species richness for these taxa along the gradient was significantly
      related to longitude but not habitat area. Communities are significantly nested,
      indicating that species-poor communities are largely composed of subsets of the
      species found on species rich reefs. These trends are robust across taxonomic
      groups except for the Pomacentridae, which exhibit an anti-nested pattern,
      perhaps due to a large number of endemic species. Correlations between life
      history traits and the number of reefs on which species occurred indicate that
      dispersal and survival ability contribute to determining community structure. We
      conclude that distance from the Coral Triangle dominates community structure in
      reef fish; however, conservation of the most species-rich areas will not be
      sufficient alone to conserve the vivid splendor of this region.

PMID- 29069098
TI  - Exploration of human brain tumour metabolism using pairwise metabolite-metabolite
      correlation analysis (MMCA) of HR-MAS 1H NMR spectra.
AB  - METHODS: We quantified 378 HRMAS 1H NMR spectra of human brain tumours (132
      glioblastomas, 101 astrocytomas, 75 meningiomas, 37 oligodendrogliomas and 33
      metastases) from the eTumour database and looked for metabolic interactions by
      metabolite-metabolite correlation analysis (MMCA). RESULTS: All tumour types
      showed remarkably similar metabolic correlations. Lactate correlated positively
      with alanine, glutamate with glutamine; creatine + phosphocreatine (tCr)
      correlated positively with lactate, alanine and choline + phosphocholine +
      glycerophosphocholine (tCho), and tCho correlated positively with lactate; fatty
      acids correlated negatively with lactate, glutamate + glutamine (tGlut), tCr and
      tCho. Oligodendrogliomas had fewer correlations but they still fitted that
      pattern. CONCLUSIONS: Possible explanations include (i) glycolytic tumour cells
      (the Warburg effect) generating pyruvate which is converted to lactate, alanine,
      glutamate and then glutamine; (ii) an association between elevated glycolysis and
      increased choline turnover in membranes; (iii) an increase in the tCr pool to
      facilitate phosphocreatine-driven glutamate uptake; (iv) lipid signals come from
      cytosolic lipid droplets in necrotic or pre-necrotic tumour tissue that has lower
      concentrations of anabolic and catabolic metabolites. Additional metabolite
      exchanges with host cells may also be involved. If tumours co-opt a standard set
      of biochemical mechanisms to grow in the brain, then drugs might be developed to
      disrupt those mechanisms.

PMID- 29069097
TI  - Muscle contributions to the acceleration of the whole body centre of mass during
      recovery from forward loss of balance by stepping in young and older adults.
AB  - The purpose of this study was to determine the muscular contributions to the
      acceleration of the whole body centre of mass (COM) of older compared to younger
      adults that were able to recover from forward loss of balance with a single step.
      Forward loss of balance was achieved by releasing participants (14 older adults
      and 6 younger adults) from a static whole-body forward lean angle of
      approximately 18 degrees. 10 older adults and 6 younger adults were able to
      recover with a single step and included in subsequent analysis. A scalable
      anatomical model consisting of 36 degrees-of-freedom was used to compute
      kinematics and joint moments from motion capture and force plate data. Forces for
      92 muscle actuators were computed using Static Optimisation and Induced
      Acceleration Analysis was used to compute individual muscle contributions to the
      three-dimensional acceleration of the whole body COM. There were no significant
      differences between older and younger adults in step length, step time, 3D COM
      accelerations or muscle contributions to 3D COM accelerations. The stance and
      stepping leg Gastrocnemius and Soleus muscles were primarily responsible for the
      vertical acceleration experienced by the COM. The Gastrocnemius and Soleus from
      the stance side leg together with bilateral Hamstrings accelerated the COM
      forwards throughout balance recovery while the Vasti and Soleus of the stepping
      side leg provided the majority of braking accelerations following foot contact.
      The Hip Abductor muscles provided the greatest contribution to medial-lateral
      accelerations of the COM. Deficits in the neuromuscular control of the
      Gastrocnemius, Soleus, Vasti and Hip Abductors in particular could adversely
      influence balance recovery and may be important targets in interventions to
      improve balance recovery performance.

PMID- 29069100
TI  - Gut microbiome of mothers delivering prematurely shows reduced diversity and
      lower relative abundance of Bifidobacterium and Streptococcus.
AB  - OBJECTIVE: Preterm birth is the main reason for neonatal deaths worldwide. We
      investigate whether maternal gut microbiota may play a previously overlooked
      role. METHODS: The Norwegian Microbiota Study (NoMIC) is a case control study on
      preterm birth (<259 days of gestation, calculated primarily based on the last
      menstrual period), including two consecutively born term infants per infant born
      prematurely. Eligible mothers were fluent in Norwegian and recruited from the
      maternity ward at a county hospital in Eastern Norway in the period 2002-2005.
      Fecal samples were collected at day 4 postpartum, and analyzed using 16S
      ribosomal RNA gene sequencing. We used samples from 121 mothers giving birth
      vaginally. Measures of alpha diversity (Shannon, Phylogenetic Diversity and
      Observed Operational Taxonomic Units) and microbiome composition were combined
      with information from the Medical Birth Registry, pregnancy journals, and
      questionnaires. RESULTS: The association between maternal gut diversity and
      preterm delivery was examined using logistic regression. One IQR increase in
      Shannon diversity was significantly associated with 38% lower odds of spontaneous
      preterm birth, (95% confident interval (CI): 1%, 61%), and the association was
      stronger when adjusting for maternal age, marital status, ethnicity, parity, BMI,
      education, antibiotic use, pets in the household, income and smoking (48% lower
      odds, 95% CI: 4.2%, 72%). Mothers delivering prematurely also had lower abundance
      of OTUs belonging to Bifidobacterium and Streptococcus, and of the Clostridiales
      order. CONCLUSION: Analysis of maternal gut microbiota using next-generation
      sequencing shows that low gut diversity, with a distinct microbial composition,
      is associated with spontaneous preterm delivery.

PMID- 29069099
TI  - The responses of an anaerobic microorganism, Yersinia intermedia MASE-LG-1 to
      individual and combined simulated Martian stresses.
AB  - The limits of life of aerobic microorganisms are well understood, but the
      responses of anaerobic microorganisms to individual and combined extreme
      stressors are less well known. Motivated by an interest in understanding the
      survivability of anaerobic microorganisms under Martian conditions, we
      investigated the responses of a new isolate, Yersinia intermedia MASE-LG-1 to
      individual and combined stresses associated with the Martian surface. This
      organism belongs to an adaptable and persistent genus of anaerobic microorganisms
      found in many environments worldwide. The effects of desiccation, low pressure,
      ionizing radiation, varying temperature, osmotic pressure, and oxidizing chemical
      compounds were investigated. The strain showed a high tolerance to desiccation,
      with a decline of survivability by four orders of magnitude during a storage time
      of 85 days. Exposure to X-rays resulted in dose-dependent inactivation for
      exposure up to 600 Gy while applied doses above 750 Gy led to complete
      inactivation. The effects of the combination of desiccation and irradiation were
      additive and the survivability was influenced by the order in which they were
      imposed. Ionizing irradiation and subsequent desiccation was more deleterious
      than vice versa. By contrast, the presence of perchlorates was not found to
      significantly affect the survival of the Yersinia strain after ionizing
      radiation. These data show that the organism has the capacity to survive and grow
      in physical and chemical stresses, imposed individually or in combination that
      are associated with Martian environment. Eventually it lost its viability showing
      that many of the most adaptable anaerobic organisms on Earth would be killed on
      Mars today.

PMID- 29069101
TI  - Breast density does not impact the ability of Videssa(r) Breast to detect breast
      cancer in women under age 50.
AB  - Breast density is associated with reduced imaging resolution in the detection of
      breast cancer. A biochemical approach that is not affected by density would
      provide an important tool to healthcare professionals who are managing women with
      dense breasts and suspicious imaging findings. Videssa(r) Breast is a
      combinatorial proteomic biomarker assay (CPBA), comprised of Serum Protein
      Biomarkers (SPB) and Tumor Associated Autoantibodies (TAAb) integrated with
      patient-specific clinical data to produce a diagnostic score that reliably
      detects breast cancer (BC) as an adjunctive tool to imaging. The performance of
      Videssa(r) Breast was evaluated in the dense (a and b) and non-dense (c and d)
      groups in a population of n = 545 women under age 50. The sensitivity and
      specificity in the dense breast group were calculated to be 88.9% and 81.2%,
      respectively, and 92.3% and 86.6%, respectively, for the non-dense group. No
      significant differences were observed in the sensitivity (p = 1.0) or specificity
      (p = 0.18) between these groups. The NPV was 99.3% and 99.1% in non-dense and
      dense groups, respectively. Unlike imaging, Videssa(r) Breast does not appear to
      be impacted by breast density; it can effectively detect breast cancer in women
      with dense and non-dense breasts alike. Thus, Videssa(r) Breast provides a
      powerful tool for healthcare providers when women with dense breasts present with
      challenging imaging findings. In addition, Videssa(r) Breast provides assurance
      to women with dense breasts that they do not have breast cancer, reducing further
      anxiety in this higher risk patient population.

PMID- 29069102
TI  - Enduring impact of conflict on mental health and gender-based violence
      perpetration in Bougainville, Papua New Guinea: A cross-sectional study.
AB  - BACKGROUND: Violence against women is often exacerbated by war, but most civilian
      research has investigated short term impact. We describe the conflict experiences
      of men and women from the general population of Bougainville Papua New Guinea,
      perceptions of the enduring impact of conflict, and the associations between
      these and the major health and development problems on the islands: mental ill
      health and violence against women. METHODS: Fourteen years after the end of the
      decade long civil war, we conducted a household survey with a random sample of
      adult (n = 864) men and (n = 879) women living in Bougainville. The interviews
      were mostly conducted face-to-face, with very sensitive questions self-completed.
      RESULTS: Mental ill-health was highly prevalent, 37.8% of women and 32% of men
      had high levels of depressive symptomatology, 34.4% of men abused alcohol and
      15.1% of women and 24.6% of men had high levels of PTSD symptoms. Among women,
      23.3% had been raped in the year prior to the interview and 33.3% had experience
      physical or sexual partner violence. The prevalence of exposure to trauma during
      the civil war was very high and many of the men and women experienced lingering
      impact of conflict. Multiple logistic regression models showed that war trauma
      was associated with PTSD symptoms in women and PTSD symptoms, alcohol abuse and
      depressive symptoms in men. The perceived enduring impact of conflict was
      associated with depressive symptoms in men and women, problem drinking and
      suicidal thoughts in women and drug use in men. The perceived enduring conflict
      impact was associated with perpetration of past year rape and physical and/or
      sexual partner violence. DISCUSSION: The Bougainville civil war had a devastating
      impact on the population's lives. Reversing this legacy is essential but requires
      addressing what is perceived as the enduring social, economic and psychological
      impact of the conflict and a major focus on prevention of violence against women.

PMID- 29069104
TI  - Reassessing the environmental context of the Aitape Skull - The oldest tsunami
      victim in the world?
AB  - There is increasing recognition of the long-lasting effects of tsunamis on human
      populations. This is particularly notable along tectonically active coastlines
      with repeated inundations occurring over thousands of years. Given the often high
      death tolls reported from historical events though it is remarkable that so few
      human skeletal remains have been found in the numerous palaeotsunami deposits
      studied to date. The 1929 discovery of the Aitape Skull in northern Papua New
      Guinea and its inferred late Pleistocene age played an important role in
      discussions about the origins of humans in Australasia for over 25 years until it
      was more reliably radiocarbon dated to around 6000 years old. However, no similar
      attention has been given to reassessing the deposit in which it was found-a
      coastal mangrove swamp inundated by water from a shallow sea. With the benefit of
      knowledge gained from studies of the 1998 tsunami in the same area, we conclude
      that the skull was laid down in a tsunami deposit and as such may represent the
      oldest known tsunami victim in the world. These findings raise the question of
      whether other coastal archaeological sites with human skeletal remains would
      benefit from a re-assessment of their geological context.

PMID- 29069105
TI  - Perils and limitations of modern-era medical communications.

PMID- 29069103
TI  - The yeast form of the fungus Candida albicans promotes persistence in the gut of
      gnotobiotic mice.
AB  - Many microorganisms that cause systemic, life-threatening infections in humans
      reside as harmless commensals in our digestive tract. Yet little is known about
      the biology of these microbes in the gut. Here, we visualize the interface
      between the human commensal and pathogenic fungus Candida albicans and the
      intestine of mice, a surrogate host. Because the indigenous mouse microbiota
      restricts C. albicans settlement, we compared the patterns of colonization in the
      gut of germ free and antibiotic-treated conventionally raised mice. In contrast
      to the heterogeneous morphologies found in the latter, we establish that in germ
      free animals the fungus almost uniformly adopts the yeast cell form, a proxy of
      its commensal state. By screening a collection of C. albicans transcription
      regulator deletion mutants in gnotobiotic mice, we identify several genes
      previously unknown to contribute to in vivo fitness. We investigate three of
      these regulators-ZCF8, ZFU2 and TRY4-and show that indeed they favor the yeast
      form over other morphologies. Consistent with this finding, we demonstrate that
      genetically inducing non-yeast cell morphologies is detrimental to the fitness of
      C. albicans in the gut. Furthermore, the identified regulators promote adherence
      of the fungus to a surface covered with mucin and to mucus-producing intestinal
      epithelial cells. In agreement with this result, histology sections indicate that
      C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus,
      our findings reveal a set of regulators that endows C. albicans with the ability
      to endure in the intestine through multiple mechanisms.

PMID- 29069106
TI  - The impact of anonymity on psychiatric patients' ratings of satisfaction with the
      initial evaluation.
AB  - BACKGROUND: Preserving anonymity is believed to yield more honest appraisals of
      patient satisfaction, although the data addressing this issue are sparse. The
      goal of this study from the Rhode Island Methods to Improve Diagnostic Assessment
      and Services project was to determine the impact of anonymity on patient
      satisfaction ratings after the initial evaluation. METHODS: The Clinically Useful
      Patient Satisfaction Scale (CUPSS) is a brief, self-administered questionnaire
      assessing patients' satisfaction with the initial evaluation. Every 2 to 3
      months, we switched from anonymous to non-anonymous completion of the CUPSS. More
      than 1,300 patients completed the scale (729 anonymous, 603 non-anonymous).
      RESULTS: Anonymity was not associated with scores on the scale. In both the
      anonymous and non-anonymous conditions, the CUPSS had high internal consistency,
      all item-scale correlations were significant, and all items were significantly
      correlated with global satisfaction ratings. There was sufficient variability in
      satisfaction ratings to detect differences among clinicians. CONCLUSIONS:
      Anonymity was not associated with patient satisfaction ratings, did not affect
      the psychometric properties of the scale, and did not compromise the scale's
      ability to discriminate among clinicians. That is, anonymity did not affect the
      reliability or validity of satisfaction ratings.

PMID- 29069108
TI  - The prevalence, characteristics, and correlates of anger among survivors of the
      9/11 World Trade Center attacks.
AB  - BACKGROUND: Anger is a prominent and common emotion in postdisaster settings.
      However, there has been little systematic investigation of the association of
      anger with psychopathology or other individual characteristics in disaster
      survivors. This study examined anger responses reported by disaster survivors and
      correlates of that anger. METHODS: Structured interviews were conducted with a
      volunteer sample of 379 employees of 7 agencies that were highly affected by the
      September 11, 2001, terrorist attacks on the World Trade Center in New York City.
      Individuals were asked about their level of anger toward various entities and
      their coping methods after the disaster. Assessments were made for disaster
      related posttraumatic stress disorder and other psychiatric disorders using the
      Diagnostic Interview Schedule for DSM-IV. Specifics of disaster trauma exposure
      were assessed using the Disaster Supplement. RESULTS: Anger was prevalent but was
      not associated with disaster trauma exposure. Anger was generally associated with
      lower level of education, younger age, and racial minority group membership, and
      was more prominent in survivors with indicators of post-disaster mental health
      problems. CONCLUSIONS: Anger may serve as an identifier of individuals at risk
      for psychopathology or who are at least highly distressed. There are potential
      implications for risk communication to address anger in the post-disaster
      setting.

PMID- 29069109
TI  - Clinical repetitive transcranial magnetic stimulation for veterans with major
      depressive disorder.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is a relatively
      new treatment modality for patients with major depressive disorder (MDD).
      Numerous studies have demonstrated the efficacy of TMS for MDD in the general
      population. However, there is limited information regarding clinical outcomes
      among veterans receiving TMS for MDD. METHODS: The clinical outcome and
      characteristics of all veterans with MDD who were treated with TMS as outpatients
      at the James A. Haley Veterans' Hospital from October 2013 to December 2016 were
      assessed. RESULTS: Among 40 patients who received TMS, there was a significant
      improvement of depressive symptoms using the Quick Inventory of Depressive
      Symptomatology-Self-Report (45% response, 20% remission) and the Montgomery
      Asberg Depression Rating Scale (61.9% response, 42.9% remission). In addition to
      significant improvement in depressive symptoms, self-report of anxiety symptoms
      and function significantly improved. TMS was generally well tolerated, with only
      a small percentage of patients discontinuing treatment due to side effects. No
      seizures or persistent adverse effects were observed or reported. CONCLUSIONS:
      TMS is an effective and well-tolerated option for MDD in a veteran population
      with significant treatment resistance and multiple comorbidities.

PMID- 29069107
TI  - The Generalized Anxiety Disorder 7-item scale in adolescents with generalized
      anxiety disorder: Signal detection and validation.
AB  - BACKGROUND: In pediatric patients with anxiety disorders, existing symptom
      inventories are either not freely available or require extensive time and effort
      to administer. We sought to evaluate a brief self-report scale-the Generalized
      Anxiety Disorder 7-item scale (GAD-7)-in adolescents with generalized anxiety
      disorder (GAD). METHODS: The Pediatric Anxiety Rating Scale (PARS) and the GAD-7
      were administered to youth with GAD (confirmed by structured interview).
      Relationships between the measures were assessed, and sensitivity and specificity
      was determined with regard to a global symptom severity measure (Clinical Global
      Impression-Severity). RESULTS: In adolescents with GAD (N = 40; mean age, 14.8 +/
      2.8), PARS and GAD-7 scores strongly correlated (R = 0.65, P <= .001) and a main
      effect for symptom severity was observed (P <= .001). GAD-7 scores >=11 and >=17
      represented the optimum specificity and sensitivity for detecting moderate and
      severe anxiety, respectively. CONCLUSIONS: The PARS and GAD-7 similarly reflect
      symptom severity. The GAD-7 is associated with acceptable specificity and
      sensitivity for detecting clinically significant anxiety symptoms. GAD-7 scores
      may be used to assess anxiety symptoms and to differentiate between mild and
      moderate GAD in adolescents, and may be more efficient than the PARS.

PMID- 29069110
TI  - Vortioxetine for major depressive disorder, vasomotor, and cognitive symptoms
      associated with the menopausal transition.
AB  - BACKGROUND: In a preliminary trial, we assessed the efficacy of vortioxetine for
      major depressive disorder (MDD) during the menopausal transition. Secondary
      outcomes included hot flashes (HFs), anxiety, and cognitive complaints. METHODS:
      Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks
      of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Asberg
      Depression Rating Scale (MADRS) was the primary outcome measure. Secondary
      measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause
      Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI),
      Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol
      Substitution Test (DSST), and Cogstate testing. RESULTS: Of the 27 women, 24
      (88.8%) were evaluated (>=1 follow-up), and 21 (77.8%) completed the study; 1
      discontinued because of adverse effects. The mean MADRS score decreased
      significantly (P = .0001) from 31.3 (standard deviation [SD] = 5.5) at
      pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate
      (>=50% reduction in MADRS) and remission rate (final MADRS <=10) were 75% and
      70.8%, respectively. GCS, MEN-QOL, BAI, CPFQ, and DSST scores improved
      significantly (P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133,
      respectively); Cogstate test scores did not. Frequency and severity of HFs
      improved significantly (P = .0291 and P = .0299, respectively). CONCLUSIONS:
      These data support further study of vortioxetine for treating menopausal
      depression and associated symptoms.

PMID- 29069111
TI  - Suicidality in psychiatrically hospitalized children and adolescents:
      Demographics, treatment, and outcome.
AB  - BACKGROUND: Despite the high prevalence of suicidality in psychiatrically
      hospitalized youth, its risk factors and impact on inpatient psychopharmacologic
      treatment are unknown. We identified characteristics associated with suicidality
      in psychiatrically hospitalized youth and determined the association of
      suicidality with subsequent psychopharmacologic interventions. METHODS: Medical
      records from consecutive psychiatric admissions to a large, acute care, urban,
      pediatric hospital were analyzed retrospectively (N = 1,309). Demographic,
      clinical, and treatment-related features of suicidal and nonsuicidal youth were
      characterized. Logistic regression identified predictors of suicidality, and
      multiple comparison analyses evaluated the association between suicidality and
      changes to antidepressant prescribing during inpatient course. RESULTS: Compared
      with nonsuicidal patients, inpatients who were suicidal were more likely to have
      a mood disorder or posttraumatic stress disorder, as well as Cannabis and alcohol
      use, were more commonly girls, and at least 13 years of age (all P <= .05).
      Hospitalization was shorter for suicidal patients, was more likely to be
      associated with antidepressant treatment (P <= .001), and among suicidal patients
      prescribed antidepressants at the time of admission, was associated with a
      greater likelihood of changing antidepressant treatment compared with nonsuicidal
      inpatients (P <= .05). CONCLUSIONS: These findings reveal differences between
      suicidal and nonsuicidal psychiatrically hospitalized youth and suggest that
      suicidality is associated with specific pharmacologic treatment approaches within
      this population.

PMID- 29069112
TI  - Systematic review of recent guidelines for pharmacological treatments of bipolar
      disorders in adults.
AB  - BACKGROUND: To examine the similarities and differences among practice guidelines
      for managing bipolar disorders (BDs) in adults. METHODS: A literature search in
      PubMed/Medline was performed using multiple search terms and bibliographies for
      guidelines from July 2013 (since FDA approval of lurasidone) to June 2017.
      RESULTS: Six treatment guidelines for BDs in adults were identified. These
      guidelines showed consensus on first-line treatment of mania (moodstabilizer
      and/or an antipsychotic), and most first-line medications for bipolar depression.
      However, beyond first-line treatments, the guidelines' recommendations showed
      major differences. Some guidelines did not specify a type of BD. In addition,
      there was variability in the stages when important treatments, such as
      electroconvulsive therapy, should be considered and in the recommended treatment
      or lack of recommended treatment-for mixed episodes and features. CONCLUSIONS:
      This review found consistency across guidelines on first-line recommendations for
      treating manic and depressive episodes, but wide differences for second- and
      third-line treatments and for other phases of BD, therefore limiting the
      generation of any "meta-consensus." We recommend creating an international
      workgroup to reconcile the evidence and develop more unified international
      recommendations.

PMID- 29069113
TI  - Renal concerns relative to the use of lithium in geriatric bipolar disorder
      patients.
AB  - BACKGROUND: Lithium is a first-line treatment for bipolar disorder in geriatric
      patients; however, it has long been associated with potentially significant renal
      consequences, including chronic kidney disease (CKD). METHODS: We reviewed the
      available evidence to characterize the effects of lithium on renal function,
      provide a consensus on periodic monitoring, and propose criteria for
      transitioning an older patient with bipolar disorder and renal issues to an
      alternate medication. RESULTS: Although the evidence on lithium use, duration,
      and dosage on progression of CKD and end-stage renal disease in geriatric
      patients is mixed, there is solid evidence that patients receiving lithium
      generally have a reduced glomerular filtration rate compared with controls. The
      current guidelines for monitoring lithium use in geriatric patients are nearly
      sufficient, but adherence in clinical practice frequently falls short.
      Alternative medications for bipolar disorder in geriatric patients are generally
      considered safe and effective, but do not have the strength of evidence that
      exists in the general adult population. CONCLUSIONS: Currently, there is no
      compelling evidence that lithium should be avoided in geriatric patients;
      however, prudent monitoring strategies are recommended, with a strong
      consideration of transitioning geriatric patients with poor tolerance to an
      alternative medication.

PMID- 29069114
TI  - Concomitant calcium channel blocker and antipsychotic therapy in patients with
      schizophrenia: Efficacy analysis of the CATIE-Sz phase 1 data.
AB  - BACKGROUND: This study evaluated the influence of concomitant calcium channel
      blocker (CCB) and antipsychotic (AP) therapy on efficacy measures in patients
      with schizophrenia. METHODS: Data from the Clinical Antipsychotic Trials of
      Intervention Effectiveness in Schizophrenia study were used to evaluate the
      effect of concomitant CCB therapy on the Clinical Global Impression-Severity (CGI
      S) score, Positive and Negative Syndrome Scale (PANSS) score, and time to all
      cause discontinuation of AP treatment. Concomitant treatment participants (CCB
      plus AP) were matched with controls (AP alone) by propensity scores using a 3:1
      greedy match algorithm, then analyzed using a mixed linear effects model adjusted
      for fixed covariates. RESULTS: The least squares mean change in CGI-S scores
      revealed a significant time-by-treatment interaction term, with greater
      improvements for the concomitant treatment group (P = .03). Total PANSS score
      showed no significant difference between groups at various time periods (1, 3, 6,
      9, 12, 15, and 18 months) and time to all-cause discontinuation was also similar
      (hazard ratio 0.94, P = .73). CONCLUSIONS: Improvements in CGI-S scores over time
      suggest that concomitant CCB plus AP treatment may reduce severity of illness
      more than AP treatment alone. However, PANSS score and time to all-cause
      discontinuation of AP treatment did not demonstrate improved outcomes.

PMID- 29069115
TI  - The Enhanced Care Program: Impact of a Care Transition Program on 30-Day Hospital
      Readmissions for Patients Discharged From an Acute Care Facility to Skilled
      Nursing Facilities.
AB  - BACKGROUND: Increased acuity of skilled nursing facility (SNF) patients
      challenges the current system of care for these patients. OBJECTIVE: Evaluate the
      impact on 30-day readmissions of a program designed to enhance the care of
      patients discharged from an acute care facility to SNFs. DESIGN: An
      observational, retrospective cohort analysis of 30-day hospital readmissions for
      patients discharged to 8 SNFs between January 1, 2014, and June 30, 2015.
      SETTING: A collaboration between a large, acute care hospital in an urban
      setting, an interdisciplinary clinical team, 124 community physicians, and 8
      SNFs. PATIENTS: All patients discharged from Cedars-Sinai Medical Center to 8
      partner SNFs were eligible for participation. INTERVENTION: The Enhanced Care
      Program (ECP) involved the following 3 interventions in addition to standard
      care: (1) a team of nurse practitioners participating in the care of SNF
      patients; (2) a pharmacist-driven medication reconciliation at the time of
      transfer; and (3) educational in-services for SNF nursing staff. MEASUREMENT:
      Thirty-day readmission rate for ECP patients compared to patients not enrolled in
      ECP. RESULTS: The average unadjusted, 30-day readmission rate for ECP patients
      over the 18-month study period was 17.2% compared to 23.0% among patients not
      enrolled in ECP (P < 0.001). After adjustment for sociodemographic and clinical
      characteristics, ECP patients had 29% lower odds of being readmitted within 30
      days (P < 0.001). These effects were robust to stratified analyses, analyses
      adjusted for clustering, and balancing of covariates using propensity weighting.
      CONCLUSIONS: A coordinated, interdisciplinary team caring for SNF patients can
      reduce 30-day hospital readmissions.

PMID- 29069116
TI  - The Pipeline From Abstract Presentation to Publication in Pediatric Hospital
      Medicine.
AB  - BACKGROUND: The annual Pediatric Hospital Medicine (PHM) conference serves as a
      venue for the dissemination of research in this rapidly growing discipline. A
      measure of research validity is subsequent publication in peer-reviewed journals.
      OBJECTIVE: To identify the publication rate of abstracts submitted to the 2014
      PHM conference and determine whether presentation format was associated with
      subsequent journal publication or time to publication. METHODS: We identified
      abstracts submitted to the 2014 PHM conference. Presentation formats included
      rejected abstracts and poster and oral presentations. Abstracts subsequently
      published in journals were identified by searching the author and abstract title
      in PubMed, MedEdPORTAL, and Google Scholar. We used logistic regression and Cox
      proportional hazards models to determine if presentation format was associated
      with publication, time to publication, and publishing journal impact factor.
      RESULTS: Of 226 submitted abstracts, 19.0% were rejected, 68.0% were selected for
      posters, and 12.8% were selected for oral presentations; 36.3% were subsequently
      published within 30 months after the conference. Abstracts accepted for oral
      presentation had more than 7-fold greater odds of publication (adjusted odds
      ratio 7.8; 95% confidence interval [CI], 2.6-23.5) and a 4-fold greater
      likelihood of publication at each month (adjusted hazard ratio 4.5; 95% CI, 2.1
      9.7) compared with rejected abstracts. Median journal impact factor was
      significantly higher for oral presentations than other presentation formats (P <
      0.01). CONCLUSIONS: Abstract reviewers may be able to identify methodologically
      sound studies for presentation; however, the low overall publication rate may
      indicate that presented results are preliminary or signify a need for increased
      mentorship and resources for research development in PHM.

PMID- 29069117
TI  - Supporting Faculty Development in Hospital Medicine: Design and Implementation of
      a Personalized Structured Mentoring Program.
AB  - The guidance of a mentor can have a tremendous influence on the careers of
      academic physicians. The lack of mentorship in the relatively young field of
      hospital medicine has been documented, but the efficacy of formalized mentorship
      programs has not been well studied. We implemented and evaluated a structured
      mentorship program for junior faculty at a large academic medical center. Of the
      16 mentees who participated in the mentorship program, 14 (88%) completed
      preintervention surveys and 10 (63%) completed postintervention surveys. After
      completing the program, there was a statistically significant improvement in
      overall satisfaction within 5 specific domains: career planning, professional
      connectedness, self-reflection, research skills, and mentoring skills. All
      mentees reported that they would recommend that all hospital medicine faculty
      participate in similar mentorship programs. In this small, single-center pilot
      study, we found that the addition of a structured mentorship program based on
      training sessions that focus on best practices in mentoring was feasible and led
      to increased satisfaction in certain career domains among early-career
      hospitalists. Larger prospective studies with a longer follow-up are needed to
      assess the generalizability and durability of our findings.

PMID- 29069118
TI  - A Howling Cause of Pancytopenia.
AB  - BACKGROUND:  OBJECTIVE:  DESIGN, SETTING, PATIENTS:  INTERVENTION:  MEASUREMENTS:
      CONCLUSIONS: 

PMID- 29069119
TI  - Do Combined Pharmacist and Prescriber Efforts on Medication Reconciliation Reduce
      Postdischarge Patient Emergency Department Visits and Hospital Readmissions?
AB  - BACKGROUND: Although medication reconciliation (Med Rec) has demonstrated a
      reduction in potential adverse drug events, its effect on hospital readmissions
      remains inconclusive. OBJECTIVE: To evaluate the impact of an interprofessional
      Med Rec bundle from admission to discharge on patient emergency department visits
      and hospital readmissions (hospital visits). METHODS: The design was a
      retrospective, cohort study. Patients discharged from general internal medicine
      over a 57-month interval were identified through administrative databases.
      Patients who received an enhanced, Gold level, Med Rec bundle (including both
      admission Med Rec and interprofessional pharmacist-prescriber collaboration on
      discharge Med Rec) were assigned to the intervention group. Patients who received
      partial Med Rec services, Silver and Bronze level, comprised the control group.
      The primary outcome was hospital visits within 30 days of discharge. RESULTS:
      Over a 57-month period, 9931 unique patient visits (n = 8678 patients) met the
      study criteria. The main analysis did not detect a difference in 30-day hospital
      visits between the intervention (Gold level bundle) and control (21.25% vs
      19.26%; adjusted odds ratio, 1.06; 95% confidence interval [CI], 0.95-1.19).
      Propensity score adjustment also did not detect an effect (16.7% vs18.9%;
      relative risk of readmission, 0.88; 95% CI, 0.59-1.32). CONCLUSION: A long-term,
      observational evaluation of interprofessional Med Rec did not detect a difference
      in 30- day postdischarge patient hospital visits between patients who received
      enhanced versus partial Med Rec patient care bundles. In future prospective
      studies, researchers could focus on evaluating high-risk populations and specific
      elements of Med Rec services on avoidable, medication-related hospital admissions
      and postdischarge adverse drug events.

PMID- 29069130
TI  - The use of the Frequency Modulation System by hearing-impaired children: benefits
      from the family's perspective.
AB  - PURPOSE: To evaluate the family's perspective of benefits of the frequency
      modulation (FM) system adapted to children with sensorineural hearing loss.
      METHODS: This is a descriptive, analytical, cross-sectional study with the
      participation of family members of hearing-impaired children aged 6 to 15 years,
      users of hearing aids and/or cochlear implants, benefited with the FM system by a
      hearing health service of the Unified Health System (SUS), Brazil. The FM
      Listening Evaluation For Children questionnaire with 14 questions was used to
      evaluate the benefits of using the FM system, the characteristics of the hearing
      aids and/or cochlear implants, and the brand/model of the FM system the children
      used. RESULTS: Statistically significant differences were found between the
      questionnaire responses of FM users and non-users in all situational analyses
      (quiet, noise, auditory only, distance), with better learning performance and
      improvements and attention among FM users, from the families' point of view. No
      method was used to formally evaluate such performances. CONCLUSION: It was
      observed that, according to the parents' and guardians' perceptions, the use of
      FM systems improves the performance of hearing-impaired children in various
      acoustic situations, with special emphasis on speech recognition in noisy
      environments and at increased distances from the sound source. Although used in
      different contexts and situations, the FM system has brought greater benefits for
      the children in the school environment, according to the respondents.

PMID- 29069120
TI  - Lateral lamella of the cribriform plate, a keystone landmark: proposal for a
      novel classification system.
AB  - BACKGROUND: The aim of this study is to propose a classification of the angle
      formed by the lateral lamella of the cribriform plate (LLCP) and the horizontal
      plane passing through the cribriform plate. In particular, the angle was
      classified into class I (over 80 degrees), class II (45 to 80 degrees, and class
      III (under 45 degrees) METHODOLOGY: A total of 190 computed tomography scans were
      retrospectively reviewed in order to obtain four sets of measurements. 1) depth
      of the cribriform, 2) angle, 3) length of the LLCP, 4) width of the fovea
      ethmoidalis. The relationship among these measurements were analyzed. RESULTS:
      The angle was significantly correlated with the depth of the cribriform and the
      length of the fovea, while it was negatively correlated with the length of the
      LLCP. Significant negative correlation was also found between the length of the
      LLCP and the width of the fovea. CONCLUSIONS: This angle classification is based
      on the theoretical risk of iatrogenic injuries, but it could be helpful also in
      clinical practice by providing indirect information on the thickness of the
      anterior skull base. As the angle decreases, in fact, the portion of the anterior
      skull base composed by the LLCP, increases.

PMID- 29069131
TI  - Latin American scientific contribution to ecology.
AB  - Latin America embodies countries of special interest for ecological studies,
      given that areas with great value for biodiversity are located within their
      territories. This highlights the importance of an evaluation of ecological
      research in the Latin America region. We assessed the scientific participation of
      Latin American researchers in ecological journals, patterns of international
      collaboration, and defined the main characteristics of the articles. Although
      Latin American publications have increased in fourteen years, they accounted up
      to 9% of publications in Ecology. Brazil leaded the scientific production in
      Latin America, followed by Argentina and Mexico. In general, Latin American
      articles represented a low percentage of most journals total publication, with
      particularly low expression in high impact-factor journals. A half of the Latin
      American publications had international collaboration. Articles with more than
      five authors and with international collaboration were the most cited.
      Descriptive studies, mainly based in old theories, are still majority, suggesting
      that Ecology is in a developing stage in Latin America.

PMID- 29069132
TI  - The conservation of native priority medicinal plants in a Caatinga area in Ceara,
      northeastern Brazil.
AB  - Much of the Brazilian semiarid region faces a considerable process of degradation
      of natural resources, and ethnobotanical studies have collaborated with important
      information about the use and traditional knowledge, serving as a tool to design
      conservation strategies of native plant species. Thus, this study aimed to
      determine medicinal species meriting conservation priorities in a "Caatinga" area
      in the northeastern of Brazilian territory. The ethnobotanical data were
      collected through semi-structured interviews with key subjects selected through
      the "snowball" technique. The availability and species conservation priority was
      verified by relative density, risk of collection, local use and use of diversity
      in the forest fragment sampled. It was recorded 42 native medicinal plants and
      conservation priority score was calculated for seven species, including Mimosa
      tenuiflora, Hymenaea courbaril, Ximenia americana and Amburana cearensis need
      immediate conservation and attention, since their collection does not occur in a
      sustainable way. In order to ensure the perpetuation of the species and the
      sustainability of traditional therapeutic practice there needs to be a
      development of conservation practices of caatinga remaining to better conserve
      the species of the biome.

PMID- 29069133
TI  - Parasitic communities of Hoplosternum littorale (Hancock, 1828) as indicators of
      environmental impact.
AB  - The parasites are indicative of several biological aspects of their hosts,
      including their diet, migration, recruitment and phylogeny, but they can also be
      direct indicators of the environmental quality. Hoplosternum littorale is a fish
      that has a high commercial value in some South American countries. The fishes
      were collected from January to July 2012, in two locations of the Peixe River in
      the municipality of Anhembi, State of Sao Paulo, Brazil, which had different
      environmental and limnological characteristics (river mouth and Lagoa Cabeca de
      Boi). An amount of 30 fish specimens were captured in each location for the
      analysis of their parasitic fauna. Nine species of metazoan parasites were
      collected. Both Brillouin's diversity index and Margalef's richness index were
      greater in the Lagoa Cabeca de Boi. The ratio of heteroxenous and monoxenous
      parasite species richness (SH/SM) was higher in the Lagoa Cabeca de Boi. The
      results of the physicochemical analysis of the water showed that the mouth of the
      Peixe River can be considered an area that suffers more from anthropogenic
      actions than the Lagoa da Cabeca de Boi. Proteocephalus sp., Gyrodactylus sp.,
      Scleroductus sp. and Capillaria (Neocapillaria) pterophylli are being registered
      for the first time in this host.

PMID- 29069134
TI  - Paleoenvironmental evolution of the coastal plain of Southern Brazil:
      palynological data from a Holocene core in Santa Catarina State.
AB  - This paper presents a paleoenvironmental reconstruction from palynological
      analyses of a sedimentary core of Holocene age, drilled at municipality of
      Garopaba (Santa Catarina), Southern Brazil. A total of 46 samples was collected
      for palynological analyses in the 450 cm-long core PCSC-3, as also three samples
      for radiocarbon dating and granulometric analyses. The palynological content
      includes 84 taxa related to pollen grains of angiosperms (38) and gimnosperm (3),
      spores of pteridophyta (16) and bryophyta (2), spores of fungi (8), algae (3),
      acritarchs (3), dinoflagellate cysts (2) and microforaminiferal linings (1).
      Three specimens of acritarchs are described and illustrated in detail. Three
      palynological phases were defined based on changes in assemblages: Phase I, Phase
      II and Phase III. The Phase I is characterized as a lagoonal paleoenvironment
      with marine influence from the beginning of the sedimentation (5390 cal yr BP),
      based on occurrences of acritarchs, dinoflagellate cysts and microforaminiferal
      linings. The Phase II (3032 yr BP until 858 cal yr BP) also is characterized by a
      lagoonal paleoenvironment, however, presented decrease in percentage of marine
      elements and increase in freshwater algae record, suggesting less marine
      influence in the lagoonal body. In Phase III (last 856 years), underwater
      sedimentation prevailed, under swamp-like conditions.

PMID- 29069135
TI  - Cryopreservation of banana's cv Grand Naine in vitro rhizomes.
AB  - The preservation of banana genetic material is usually performed through
      seedlings. However, most banana cultivars do not produce seed and are propagated
      vegetatively. Therefore, cryopreservation is a feasible technique that allows the
      preservation of banana genotypes indefinitely. For the success of
      cryopreservation protocols, the selection of cryoprotectants and pre-freezing
      techniques are important factor. Therefore, the objective of this study was to
      verify the effects of different cryoprotectants with and without 1%
      phloroglucinol and pre-cooling periods on the development of a protocol for
      cryopreservation of in vitro rhizomes ofMusa accuminata(AAA) cv Grand Naine
      banana. The addition of 1% phloroglucinol to the cryoprotective solutions, such
      as PVS2 enhanced recovery of cryopreserved banana rhizomes. In addition, pre
      cooling of explants in ice for 3 hours in PVS2 + 1% of phloroglucinol allowed
      efficient cryopreservation of banana rhizomes, followed by successful recovery
      and regeneration of in vitro shoots of banana cv Grand Naine.

PMID- 29069136
TI  - Peculiar anatomical traits, high durability, and potential ornamental use of
      Cyclanthaceae as fresh foliage.
AB  - Wild plant species with potential for use as ornamental green foliage are often
      reported. Nevertheless, there are few studies evaluating morphological and
      anatomical aspects associated with this use. Preliminary trials suggest that the
      species of Sphaeradenia (Sander ex Mast.) Harling, a Cyclantaceae that occurs
      from Costa Rica to Peru, is suitable to be used as fresh foliage because of
      attractiveness of their leaves in vase and its durability without showing tissue
      damage, compared with other genera of this family. Through the study of
      anatomical characters, it is possible to predict the potential of a species that
      can serve as ornamental foliage. In this study, three foliar anatomical features
      (thickness of the cuticle and leaf, and percentage of fibers in the mesophyll) of
      seven Cyclanthaceae species were evaluated, using anatomical techniques and image
      analysis with the LUCIA(r) and ImageJ softwares. Statistical analysis of the
      results suggests that this high durability is associated with the thickness of
      the cuticle and mesophyll, but not with the amount of fibers in the leaf.

PMID- 29069137
TI  - Use of performance indicators to assess the solid waste management of health
      services.
AB  - Modern society faces serious challenges, among them, the complexity of
      environmental problems. Thus, there are several possible sources of environmental
      degradation, however, the waste produced by health services have an important
      peculiarity due to its toxic or pathogenic characteristics, since when managed
      improperly provide also health risk public. The involvement of solid waste from
      healthcare services environmental impact integrates matters a little more
      complex, because in addition to environmental health, they also interfere with
      the healthiness of environments that generate, with the consequences of
      nosocomial infections, occupational health and public. Thus, the management has
      become an urgent need, especially when we see no use of performance indicators
      management in healthcare environments in the city of Sao Mateus, ES. For this, we
      used the Analytic Hierarchy Process Method to prioritize such indicators as the
      potential improvement in health services waste management process - WHS and thus
      environmental analysis was performed with the use of a template for SWOT
      analysis. The results showed that the performance indicator training strategies
      developed with employees has the greatest potential to assist in improvements in
      WHS (Health Services Waste) management process followed indicator knowledge of
      the regulations associated with procedures performed by employees and importance
      of biosafety regulations.

PMID- 29069138
TI  - Moderate pathogenic effect of Ligophorus uruguayense (Monogenoidea,
      Ancyrocephalidae) in juvenile mullet Mugil liza (Actinopterygii, Mugilidae) from
      Brazil.
AB  - Monogenoidea pathogenic activity can elicit various histological responses in
      fish. Species of Ligophorus are specific parasites of mullets, and its
      relationship with host fish may result in a moderate pathogenic action. In order
      to ascertain this relationship, estuarine mullets (Mugil liza) were collected in
      an estuary, reared in laboratory, for three weeks, and forwarded for histological
      and parasitological analyses. Ligophorus uruguayense (Monogenoidea) infestation
      in the gills of the mullets was identified. The severe infestation by only one
      species of Monogenoidea may result from the specificity of these parasites to
      mullets. Mullets submitted to histological analysis exhibited respiratory
      epithelium detachment; mild, moderate and severe hyperplasia of the respiratory
      epithelium; atrophy; and telangiectasia of the gills. This is the first study
      reporting that mullets highly infested by Monogenoidea can show mild (100%) to
      severe (20%) gill changes with a distinct frequency of occurrence. Because of the
      high prevalence of mild alterations observed, it is possible to accept that L.
      uruguayense is moderately pathogenic to M. liza, even during high prevalence and
      intensity of infestation, as a result of its specificity.

PMID- 29069140
TI  - A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19
      oic Acid by Mucor plumbeus.
AB  - The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid
      (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid
      medium. Two products were isolated, and their structures were determined by
      spectroscopic means as 7beta-hydroxytrachyloban-19-oic acid (5) and trachyloban
      19-O-beta-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is
      herein reported by the first time in the literature. These compounds were assayed
      for acetylcholinesterase inhibition along with some related compounds. Compound 6
      showed the highest acetylcholinesterase inhibitory activity at 10000 ug/mL among
      the tested compounds, a result (92.89%) comparable to the activity of the
      positive control, galanthamine (94.21%). Therefore, biotransformation of the
      natural product 1 by M. plumbeus produced a novel compound with potential as a
      new lead to develop anti-Alzheimer medicines.

PMID- 29069139
TI  - Elemental composition of vegetables cultivated over coal-mining waste.
AB  - We assessed elemental composition of the liver in mice subjected to one-time or
      chronic consumption of the juice of vegetables cultivated in a vegetable garden
      built over deposits of coal waste. Lactuca sativa L. (lettuce), Beta vulgaris L.
      (beet), Brassica oleracea L. var. italica (broccoli) and Brassica oleracea L.
      var. acephala (kale) were collected from the coal-mining area and from a
      certified organic farm (control). Elemental composition was analyzed by particle
      induced X-ray emission (PIXE) method. Concentrations of Mg, S, and Ca of mice
      subjected to one-time consumption of broccoli and concentrations of these same
      elements plus Si of mice receiving kale were higher in the coal-mining area.
      Concentrations of P, K, and Cu were increase after chronic consumption of lettuce
      from the coal-mining area, whereas the levels of Si, P, K, Fe, and Zn were higher
      in the group consuming kale from the coal-mining area. Our data suggests that
      people consuming vegetables grown over coal wastes may ingest significant amounts
      of chemical elements that pose a risk to health, since these plants contain both
      essential and toxic metals in a wide range of concentrations, which can do more
      harm than good.

PMID- 29069141
TI  - Intra-arterial fibrinolysis for the management of acute ischemia on a below-knee
      amputation stump. Case report.
AB  - Preservation of the knee joint has enormous advantages in terms of mobility and
      rehabilitation of an amputee. Any cause of breakdown requiring revision to an
      above-knee amputation is a major setback because it reduces the patient's
      rehabilitative potential. We report a case of intra-arterial thrombolysis use to
      save a below-knee amputation stump with acute ischemia. A 56-year-old man who
      sought the emergency department with 1-day history of acute pain on his right
      below-knee stump. The angiography confirmed popliteal artery occlusion.
      Pharmacomechanical thrombectomy, with Aspirex (rotational catheter to restore
      blood flow in occluded vessel, by removing occlusion material from the vessel)
      and recombinant tissue plasminogen activator, was performed. After 9 years of
      follow-up the patient remained asymptomatic, capable of independent ambulation
      with prosthetic limb. Intra-arterial fibrinolysis seems to be a safe and
      effective treatment for cases of acutely ischemic amputation stump.

PMID- 29069142
TI  - Embedding research in health policy and systems in the Americas.

PMID- 29069144
TI  - Effect of ultrasound streaming on the disinfection of flattened root canals
      prepared by rotary and reciprocating systems.
AB  - : New technical and scientific developments have been advocated to promote the
      success of the endodontic treatment. In addition to rotary and reciprocating
      systems, irrigating solution agitation has been suggested and passive ultrasonic
      irrigation (PUI) is the most used. OBJECTIVE: To evaluate, in vitro, the effect
      of ultrasound streaming (US) in the disinfection of flattened root canal systems
      prepared by the ProTaper, BioRaCe and Reciproc systems, utilizing the
      microbiological culture. METHODOLOGY: Extracted human mandibular incisors (n=84)
      were used. Suspensions of Enterococcus faecalis (ATCC 29212) were standardized
      and inserted along with the teeth immersed in brain-heart infusion (BHI) broth.
      The contamination was made following a protocol during 5 days. The teeth were
      randomly divided into six groups: G1, ProTaper Universal; G2, ProTaper Universal
      with US; G3, BioRaCe; G4, BioRaCe with US; G5, Reciproc; and G6, Reciproc with
      US. Irrigation was performed with saline solution. After biomechanical
      preparation, microbiological samples were performed with sterilized paper points,
      which were diluted and spread on BHI agar; after 48 h, the colony forming units
      (CFU/mL) were counted for each sample. RESULTS: Groups using ultrasonic agitation
      presented a greater antibacterial effect than the other ones, even using saline
      solution as irrigant. The ProTaper Universal system showed the best antibacterial
      activity of the tested systems (median of 0 CFU/mL with and without surfactant or
      ultrasonic activation [PUI]). Even with PUI, Reciproc (median of 2.5 CFU/mL with
      PUI and 5 without it) could not reduce as many colonies as ProTaper Universal
      without US. The BioRaCe system had greater bacterial reduction when using US
      (median of 0 CFU/mL with PUI and 30 without it). CONCLUSIONS: US promoted greater
      reduction in the number of bacteria in the flattened root canals prepared with
      nickel-titanium mechanized systems. Regarding the instruments used, the ProTaper
      Universal system was the most effective in reducing the bacterial number.

PMID- 29069143
TI  - Factors affecting the periapical healing process of endodontically treated teeth.
AB  - Tissue repair is an essential process that reestablishes tissue integrity and
      regular function. Nevertheless, different therapeutic factors and clinical
      conditions may interfere in this process of periapical healing. This review aims
      to discuss the important therapeutic factors associated with the clinical
      protocol used during root canal treatment and to highlight the systemic
      conditions associated with the periapical healing process of endodontically
      treated teeth. The antibacterial strategies indicated in the conventional
      treatment of an inflamed and infected pulp and the modulation of the host's
      immune response may assist in tissue repair, if wound healing has been hindered
      by infection. Systemic conditions, such as diabetes mellitus and hypertension,
      can also inhibit wound healing. The success of root canal treatment is affected
      by the correct choice of clinical protocol. These factors are dependent on the
      sanitization process (instrumentation, irrigant solution, irrigating strategies,
      and intracanal dressing), the apical limit of the root canal preparation and
      obturation, and the quality of the sealer. The challenges affecting the healing
      process of endodontically treated teeth include control of the inflammation of
      pulp or infectious processes and simultaneous neutralization of unpredictable
      provocations to the periapical tissue. Along with these factors, one must
      understand the local and general clinical conditions (systemic health of the
      patient) that affect the outcome of root canal treatment prediction.

PMID- 29069145
TI  - Metrical analysis of disc-condyle relation with different splint treatment
      positions in patients with TMJ disc displacement.
AB  - OBJECTIVE: To evaluate the effect of bite positions characterizing different
      splint treatments (anterior repositioning and stabilization splints) on the disc
      condyle relation in patients with TMJ disc displacement with reduction (DDwR),
      using magnetic resonance imaging (MRI). MATERIAL AND METHODS: 37 patients, with a
      mean age of 18.8+/-4.3 years (7 male and 30 females) and diagnosed with DDwR
      based on the RDC/TMD, were recruited. MRI metrical analysis of the spatial
      changes of the disc/condyle, as well as their relationships, was done in three
      positions: maximum intercuspation (Position 1), anterior repositioning splint
      position (Position 2), and stabilization splint position (Position 3).
      Disc/condyle coordinate measurements and disc condyle angles were determined and
      compared. RESULTS: In Position 1, the average disc-condyle angle was 53.4 degrees
      in the 60 joints with DDwR, while it was -13.3 degrees  with Position 2 and 30.1
      degrees  with Position 3. The frequency of successful "disc recapture" with
      Position 2 was significantly higher (58/60, 96.7%) than Position 3 (20/60,
      33.3%). In Positions 2 and 3, the condyle moved forward and downward while the
      disc moved backward. The movements were, however, more remarkable with Position
      2. CONCLUSIONS: Anterior repositioning of the mandible improves the spatial
      relationship between the disc and condyle in patients with DDwR. In addition to
      anterior and inferior movement of the condyle, transitory posterior movement of
      the disc also occurred.

PMID- 29069146
TI  - Agreement, correlation, and kinetics of the alveolar bone-loss measurement
      methodologies in a ligature-induced periodontitis animal model.
AB  - : Periodontal research involves the use of animal models to better understand the
      biological processes of periodontal diseases and the potential of new or existing
      therapies. Currently, ligature-induced periodontitis in rats is the main model
      used in periodontal research, in this model, alveolar bone loss (ABL) is the main
      parameter evaluated by radiographic, morphometric, and histological techniques.
      Interestingly, although these methodologies are widely used, it is not totally
      clarified neither the kinetics of ABL over the induction time nor the agreement
      degree (repeatability and reproducibility) of these techniques. OBJECTIVE: To
      characterize ABL kinetics at 0, 3, 7, 15, 30, and 60 days after ABL induction by
      ligature and to evaluate the intra- (repeatability) and inter-examiner
      (reproducibility) agreement and the correlation among the radiographic,
      morphometric, and histological methodologies. MATERIAL AND METHODS: 60 male
      Wistar rats with induced ABL were randomly divided into 6 experimental groups (n
      = 10 animals/group). After 0, 3, 7, 15, 30, and 60 days, the animals were
      euthanized and their hemimandibles were removed for ABL determination using
      radiographic, morphometric and histological techniques. RESULTS: Radiographic and
      morphometric/linear techniques allowed the detection of statistically significant
      ABL on the third day, while histological and morphometric/area techniques could
      only detect ABL after the seventh day (ANOVA/Tukey, p<0.05). After the fifteenth
      day, except for histological analysis, the ABL was stabilized. Concerning the
      agreement of the methodologies, Bland Altman's test (intra and inter-examiner
      evaluations) showed no difference among the measurements (p>0.05). In addition,
      high correlations (Pearson's test, r2>0.9, p<0.05) were observed. CONCLUSION: The
      results indicated that the minimum time for ABL induction could vary from 3 to 7
      days, according to the chosen analysis methodology. Agreement and correlation
      data support the comparison of results between studies with same induction time.

PMID- 29069147
TI  - Effects of continual intermittent administration of parathyroid hormone on
      implant stability in the presence of osteoporosis: an in vivo study using
      resonance frequency analysis in a rabbit model.
AB  - OBJECTIVE: This study aimed to evaluate the effects of continual intermittent
      administration of parathyroid hormone (PTH) on implant stability in the presence
      of osteoporosis, using rabbit models. MATERIAL AND METHODS: Fifteen female New
      Zealand white rabbits underwent ovariectomy and were administered glucocorticoids
      to induce osteoporosis, following which they were divided into three groups. The
      first group received intermittent subcutaneous PTH for 4 weeks until implant
      placement (PTH1), while the second and third groups received PTH (PTH2) and
      saline (control), respectively, for 4 weeks before and after implant placement.
      After intermittent administration of PTH or saline, titanium implants were
      inserted into the left femoral epiphyses of all animals, and the implant
      stability quotient (ISQ) was measured immediately after placement to assess the
      primary stability and at 2 and 4 weeks after implant placement to assess
      osseointegration. At 4 weeks after implant placement, histological and
      histomorphometric evaluations were conducted and the bone area around the implant
      socket was measured as a ratio of the total bone area to the total tissue area.
      RESULTS: Regarding primary stability, the ISQ values for the PTH1 and PTH2 groups
      were significantly higher than those for the control group (p<0.05). Concerning
      osseointegration, the ISQ values at 2 and 4 weeks were significantly higher for
      the PTH2 group than for the PTH1 and control (p<0.05) groups. Histological
      assessments showed a thicker and more trabecular bone around the implant sockets
      in the PTH2 specimens than in the PTH1 and control specimens. The bone area
      around the implant socket was significantly greater in the PTH2 group than in the
      PTH1 and control groups (p<0.05). CONCLUSIONS: Our results suggest that continual
      intermittent PTH administration before and after dental implant placement is
      effective for the achievement of favorable stability and osseointegration in the
      presence of osteoporosis.

PMID- 29069148
TI  - Impact of inhalation therapy on the incidence of carious lesions in patients with
      asthma and COPD.
AB  - OBJECTIVE: The aim of this study was to investigate the incidence of carious
      lesions, the amount of salivary flow rate and pH value in patients with asthma
      and chronic obstructive pulmonary diseases (COPD), using inhalation therapy. The
      obtained results were compared with the results of adult healthy subjects,
      forming a control group. MATERIAL AND METHODS: The study included 80 participants
      aging between 18 and 65 years. The experimental group (EG) was comprised of 40
      participants, previously diagnosed with asthma or COPD undergoing inhalation
      therapy for more than five years. The control group (CG), comprised of 40
      participants, mirrored the same age and gender status of the EG. Dental status
      was determined by decayed, missing, and filled teeth (DMFT index). Quantity and
      pH value of saliva were determined in the laboratory. RESULTS: In the EG, the
      mean value of the salivary flow rate and pH value were statistically
      significantly lower than in the CG (p<0.001). Patients in the EG had a higher
      value of DMFT index when compared with the CG, although the difference was not
      statistically significant (p=0.199). Mean number of decayed teeth, as well as
      missing teeth, in the EG was statistically significantly higher than in the CG
      (p<0.001). Mean number of filled teeth in the EG was statistically significantly
      lower than in the CG (p<0.001). CONCLUSION: It was found that patients undergoing
      inhalation therapy face increasing risk of dental caries due to the lower
      salivary flow rate and pH value along with the inhalation therapy. They should
      receive intensive preventive care, including oral hygiene instruction and dietary
      advice.

PMID- 29069149
TI  - Effects of Syzygium aromaticum, Cinnamomum zeylanicum, and Salvia triloba
      extracts on proliferation and differentiation of dental pulp stem cells.
AB  - INTRODUCTION: Hypersensitivity, local irritative and cytotoxic effects are known
      for the chemical components of Syzygium aromaticum and Cinnamomum zeylanicum
      contained in dental materials. However, there is no intimate data in dentistry
      using the whole extracts of these plants and introducing new ones. Salvia triloba
      is a well-known anti-inflammatory plant that correspondingly could be used in
      several dental traumas. OBJECTIVES: We aimed to show and compare the effect of S.
      aromaticum, C. zeylanicum, and S. triloba extracts on dental pulp stem cells
      (DPSCs) proliferation, differentiation, and immune responses. MATERIAL AND
      METHODS: Using xCELLigence, a real time monitoring system, we obtained a growth
      curve of DPSCs with different concentrations of the Extracts. A dose of 10 MUg/mL
      was the most efficient concentration for vitality. Osteogenic differentiation and
      anti-inflammatory activities were determined by using an ELISA Kit to detect
      early and late markers of differentiation. RESULTS: The level of osteonectin (ON,
      early osteogenic marker) decreased, which indicated that the osteogenic
      differentiation may be accelerated with addition of extracts. However, the level
      of osteocalcin (OCN, late osteogenic marker and sign of calcium granulation)
      differed among the extracts, in which S. aromaticum presented the highest value,
      followed by S. triloba and C. zeylanicum. Surprisingly, the determined calcium
      granules were reduced in S. aromaticum and S. triloba. In response to tumor
      necrosis factor alpha (TNF-alpha), S. triloba-treated DPSCs showed the most
      reduced level of IL-6 cytokine level. We suggest C. zeylanicum as a promising
      osteogenic inducer and S. triloba as a potent anti-inflammatory agent, which
      could be used safely in biocomposite or scaffold fabrications for dentistry.
      CONCLUSIONS: Because calcium granule formation and cell viability play a critical
      role in hard tissue formation, S. aromaticum in dentistry should be strictly
      controlled, and the mechanism leading to reduced calcium granule formation should
      be identified.

PMID- 29069150
TI  - Rubbing time and bonding performance of one-step adhesives to primary enamel and
      dentin.
AB  - OBJECTIVES: This study investigated whether increasing the concentration of
      acidic monomers in one-step adhesives would allow reducing their application time
      without interfering with the bonding ability to primary enamel and dentin.
      MATERIAL AND METHODS: Experimental one-step self-etch adhesives were formulated
      with 5 wt% (AD5), 20 wt% (AD20), or 35 wt% (AD35) acidic monomer. The adhesives
      were applied using rubbing motion for 5, 10, or 20 s. Bond strengths to primary
      enamel and dentin were tested under shear stress. A commercial etch-and-rinse
      adhesive (Single Bond 2; 3M ESPE) served as reference. Scanning electron
      microscopy was used to observe the morphology of bonded interfaces. Data were
      analysed at p<0.05. RESULTS: In enamel, AD35 had higher bond strength when rubbed
      for at least 10 s, while application for 5 s generated lower bond strength. In
      dentin, increased acidic monomer improved bonding only for 20 s rubbing time. The
      etch-and-rinse adhesive yielded higher bond strength to enamel and similar
      bonding to dentin as compared with the self-etch adhesives. The adhesive layer
      was thicker and more irregular for the etch-and-rinse material, with no
      appreciable differences among the self-etch systems. CONCLUSION: Overall,
      increasing the acidic monomer concentration only led to an increase in bond
      strength to enamel when the rubbing time was at least 10 s. In dentin, despite
      the increase in bond strength with longer rubbing times, the results favoured the
      experimental adhesives compared to the conventional adhesive. Reduced rubbing
      time of self-etch adhesives should be avoided in the clinical setup.

PMID- 29069151
TI  - Dentin pretreatment and adhesive temperature as affecting factors on bond
      strength of a universal adhesive system.
AB  - OBJECTIVES: To evaluate the effects of dentin pretreatment and temperature on the
      bond strength of a universal adhesive system to dentin. MATERIAL AND METHODS:
      Ninety-six extracted non-carious human third molars were randomly divided into 12
      groups (n=8) according to Scotchbond Universal Adhesive (SbU) applied in self
      etch (SE) and etch-and-rinse (ER) mode, adhesive temperature (20 degrees C or 37
      degrees C) and sodium bicarbonate or aluminum oxide air abrasion. After composite
      build up, bonded sticks with cross-sectional area of 1 mm2 were obtained to
      evaluate the microtensile bond strength (MUTBS). The specimens were tested at a
      crosshead speed of 0.5 mm/min on a testing machine until failure. Fractured
      specimens were analyzed under stereomicroscope to determine the failure patterns
      in adhesive, cohesive (dentin or resin) and mixed fractures. The microtensile
      bond strength data was analyzed using two-way ANOVA and Tukey's test (alpha=5%).
      RESULTS: Interaction between treatment and temperature was statistically
      significant for SbU applied in self-etch technique. Both dentin treatments showed
      higher bond strength for ER mode, regardless of adhesive temperature. When
      compared to control group, sodium bicarbonate increased bond strength of SbU in
      SE technique. Adhesive temperature did not significantly affect the MUTBS of
      tested groups. Predominantly, adhesive failure was observed for all groups.
      CONCLUSIONS: Dentin surface treatment with sodium bicarbonate air abrasion
      improves bond strength of SbU, irrespective of adhesive application mode, which
      makes this approach an alternative to increase adhesive performance of Scotchbond
      Universal Adhesive to dentin.

PMID- 29069152
TI  - In vitro and in vivo evaluations of glass-ionomer cement containing chlorhexidine
      for Atraumatic Restorative Treatment.
AB  - OBJECTIVES: Addition of chlorhexidine has enhanced the antimicrobial effect of
      glass ionomer cement (GIC) indicated to Atraumatic Restorative Treatment (ART);
      however, the impact of this mixture on the properties of these materials and on
      the longevity of restorations must be investigated. The aim of this study was to
      evaluate the effects of incorporating chlorhexidine (CHX) in the in vitro
      biological and chemical-mechanical properties of GIC and in vivo clinical/
      microbiological follow-up of the ART with GIC containing or not CHX. MATERIAL AND
      METHODS: For in vitro studies, groups were divided into GIC, GIC with 1.25% CHX,
      and GIC with 2.5% CHX. Antimicrobial activity of GIC was analyzed using agar
      diffusion and anti-biofilm assays. Cytotoxic effects, compressive tensile
      strength, microhardness and fluoride (F) release were also evaluated. A
      randomized controlled trial was conducted on 36 children that received ART either
      with GIC or GIC with CHX. Saliva and biofilm were collected for mutans
      streptococci (MS) counts and the survival rate of restorations was checked after
      7 days, 3 months and one year after ART. ANOVA/Tukey or Kruskal-Wallis/ Mann
      Whitney tests were performed for in vitro tests and in vivo microbiological
      analysis. The Kaplan-Meier method and Log rank tests were applied to estimate
      survival percentages of restorations (p<0.05). RESULTS: Incorporation of 1.25%
      and 2.5% CHX improved the antimicrobial/anti-biofilm activity of GIC, without
      affecting F release and mechanical characteristics, but 2.5% CHX was cytotoxic.
      Survival rate of restorations using GIC with 1.25% CHX was similar to GIC. A
      significant reduction of MS levels was observed for KM+CHX group in children
      saliva and biofilm 7 days after treatment. CONCLUSIONS: The incorporation of
      1.25% CHX increased the in vitro antimicrobial activity, without changing
      chemical-mechanical properties of GIC and odontoblast-like cell viability. This
      combination improved the in vivo short-term microbiological effect without
      affecting clinical performance of ART restorations.

PMID- 29069153
TI  - Comparison of two combinations of opioid and non-opioid analgesics for acute
      periradicular abscess: a randomized clinical trial.
AB  - INTRODUCTION: Acute periradicular abscess is a condition characterized by the
      formation and propagation of pus in the periapical tissues and generally
      associated with debilitating pain. OBJECTIVE: The aim of this study was to
      compare the overall analgesic effectiveness of two combinations of opioid and non
      opioid analgesics for acute periradicular abscess. MATERIAL AND METHODS: This
      study included 26 patients who sought emergency care in a Brazilian dental
      school. The patients were randomly divided into two groups: Co/Ac - oral
      prescription of codeine (30 mg) plus acetaminophen (500 mg), every 4 h, for 3
      days or Tr/Ac - oral prescription of tramadol hydrochloride (37.5 mg) plus
      acetaminophen (500 mg) on the same schedule. Two factors were evaluated: (1) pain
      scores recorded by the patients in a pain diary 6, 12, 24, 48, and 72 h after
      treatment, using the Visual Analogue Scale; and (2) the occurrence of adverse
      effects. RESULTS: In both groups, there was a reduction in pain scores over time.
      For the Co/Ac group, there was a significant reduction in the scores 12, 24, 48,
      and 72 hours after treatment (P<0.05). In the Tr/Ac group, the scores
      significantly decreased over time from time point 6 h (P<0.05). Comparing the
      pain at each time point, the groups were not significantly different (P>0.05),
      i.e., both treatments were effective in controlling pain caused by APA; however,
      the combination of Tr/Ac caused more adverse reactions as two patients had to
      stop using the medication. CONCLUSION: This study suggests that, considering both
      analgesic efficacy and safety, the combination of codeine and acetaminophen is
      more effective to control moderate to severe pain from acute periradicular
      abscesses.

PMID- 29069154
TI  - Assessment of the accuracy of portable monitors for halitosis evaluation in
      subjects without malodor complaint. Are they reliable for clinical practice?
AB  - : Halitosis is defined as a foul odor emanated from the oral cavity, with great
      impact in quality of life and social restraints. Recently, the use of Breath
      AlertTM in research increased significantly. HalimeterTM, another portable
      device, is often used in clinical practice. Nevertheless, not many studies have
      verified the accuracy and compared the results of both devices simultaneously.
      OBJECTIVE: To verify the accuracy of Breath AlertTM and HalimeterTM in patients
      without chief complaint of halitosis, using the organoleptic test (OT) as "gold
      standard." The second aim was to verify whether their concomitant use could
      enhance the diagnostic accuracy of halitosis. MATERIAL AND METHODS: A cross
      sectional analytical study was performed. The quality of expired air of 34
      subjects without chief complaint of halitosis was assessed. Two experienced
      examiners carried out the OT. Afterward, a third blinded examiner performed
      HalimeterTM (HT) and Breath AlertTM (BA) tests. RESULTS: The OT identified
      halitosis in 21 subjects (62%). The area under the ROC curve (95% confidence
      interval) was 0.67 (0.48-0.85) and 0.54 (0.34-0.75) for HT and BA, respectively.
      The accuracy for HT and BA was 59% and 47%, respectively. The combined usage of
      HT and BA provided 11 positive results, being 9 subjects (43%) out of the total
      of 21 positive cases. CONCLUSIONS: HalimeterTM and Breath AlertTM were not able
      to diagnose halitosis in non-complainer subjects at the same level as the
      organoleptic examination, since their accuracy were low. Our results suggest that
      such portable devices are not reliable tools to assess halitosis and may neglect
      or misdiagnose a considerable number of patients in clinical practice.

PMID- 29069157
TI  - In vitro efficacy of Duddingtonia flagrans against nematodes of sheep based on in
      vivo calculations.
AB  - Duddingtonia flagrans has been tested as an alternative parasite control, but
      data from in vitro experiments based on in vivo calculations describing
      nematophagous fungi predation in nematodes are restricted. The objective of this
      work was to determine the efficacy of D. flagrans against sheep nematode larvae
      in vitro using in vivo calculations. Fecal samples were introduced to fungi in
      different concentrations: 0.0/control; 0.05; 0.1; 0.2; 0.4; 0.8; 1.6; 3.2; and
      6.4 g corresponding, respectively, to 583.000; 1.166.000; 2.332.000; 4.664.000;
      9.328.000; 18.656.000; 37.312.000 and 74.624.000 chlamydospores/kg of body
      weight. The material was incubated for 14 days, before the larvae recovery (Assay
      1). Assay 2 was carried out with the doses of 0.00625; 0.0125; and 0.025 g. The
      results showed a negative correlation between fungal concentrations and larval
      numbers for both assays. The fungus demonstrated an efficacy above 89% in both
      assays. Thus, we consider that the data from in vitro studies based on in vivo
      calculations may optimize the fungi quantities for field experiments.

PMID- 29069156
TI  - Effectiveness of a new non-hydrogen peroxide bleaching agent after single use - a
      double-blind placebo-controlled short-term study.
AB  - INTRODUCTION: Tooth whitening represents perhaps the most common aesthetic
      procedure in dentistry worldwide. The efficacy of bleaching depends on three
      aspects: bleaching agent, bleaching method, and tooth color. OBJECTIVE: This in
      vivo study aimed to examine whitening effects on frontal teeth of the upper and
      lower jaws using an over-the-counter (OTC) non-hydrogen peroxide bleaching agent
      in comparison to a placebo after one single use. MATERIAL AND METHODS: Forty
      subjects (25 female; 15 male) participated in this double-blind randomized
      placebo-controlled trial. The subjects were randomly allocated to two groups
      (n=20). The test group received the OTC product (iWhite Instant) and the placebo
      group received an identically composed product except for the active agents. Each
      subject was treated with a prefilled tray containing iWhite Instant or the
      placebo for 20 minutes. The tooth shade of the front teeth (upper and lower jaws)
      was assessed before (E_0), immediately after (E_1) and 24 h after treatment
      (E_2), using a shade guide (VITA classical). Statistical testing was accomplished
      using the Mann-Whitney U test (p<0.001). The dropout rate was 0%. RESULTS: There
      were no significant differences at E_0 between placebo and test groups regarding
      the tooth color. Differences in tooth color changes immediately after (DeltaE1_0)
      and 24 h after treatment (DeltaE2_0) were calculated for both groups. The mean
      values (standard deviations) of tooth color changes for DeltaE1_0 were 2.26
      (0.92) in the test group and 0.01 (0.21) in the placebo group. The color changes
      for DeltaE2_0 showed mean values of 2.15 (1.10) in the test group and 0.07 (0.35)
      in the placebo group. For DeltaE1_0 and DeltaE2_0 significant differences were
      found between the groups. CONCLUSION: In this short-term study, the results
      showed that a non-hydrogen peroxide bleaching agent has significant whitening
      effects immediately and 24 h after a single-use treatment.

PMID- 29069155
TI  - Effects of porcelain thickness on the flexural strength and crack propagation in
      a bilayered zirconia system.
AB  - OBJECTIVE: This study evaluated the influence of porcelain (VM9, VITA Zahnfabrik,
      Germany) thickness on the flexural strength and crack propagation in bilayered
      zirconia systems (YZ, VITA Zahnfabrik, Germany). MATERIAL AND METHODS: Thirty
      zirconia bars (20.0x4.0x1.0 mm) and six zirconia blocks (12.0x7.5x1.2 mm) were
      prepared and veneered with porcelain with different thickness: 1 mm, 2 mm, or 3
      mm. The bars of each experimental group (n=10) were subjected to four-point
      flexural strength testing. In each ceramic block, a Vickers indentation was
      created under a load of 10 kgf for 10 seconds, for the propagation of cracks.
      RESULTS: The results of flexural strength were evaluated by One-way ANOVA and
      Tukey's test, with a significance level of 5%. The factor "thickness of the
      porcelain" was statistically significant (p=0.001) and the l-mm group presented
      the highest values of flexural strength. The cracks were predominant among the
      bending specimens with 1 and 2 mm of porcelain, and catastrophic failures were
      found in 50% of 3-mm-thick porcelain. After the indentation of blocks, the most
      severe defects were observed in blocks with 3-mm-thick porcelain. CONCLUSION: The
      smallest (1 mm) thickness of porcelain on the zirconia infrastructure presented
      higher values of flexural strength. Better resistance to defect propagation was
      observed near the porcelain/ zirconia interface for all groups. Higher flexural
      strength was found for a thinner porcelain layer in a bilayered zirconia system.
      The damage caused by a Vickers indentation near and far the interface with the
      zirconia shows that the stress profiles are different.

PMID- 29069158
TI  - Multiple anthelmintic resistance in Southern Brazil sheep flocks.
AB  - Gastrointestinal parasites represent an important cause of reduced productivity
      of sheep worldwide. As anthelmintic are still the main control tool for these
      parasites, this work evaluated the efficacy of commercially available active
      principles in 22 sheep flocks in the southern region of Rio Grande do Sul,
      Brazil. In each farm 10 sheep were randomly distributed in seven groups with the
      following treatments: abamectin; albendazole; closantel; levamisole; monepantel;
      trichlorphon and no anthelmintic (control). All flocks showed resistance to at
      least three anthelmintics and in 20 farms only two products demonstrated efficacy
      for parasitic control. In two farms, there was no susceptibility to the six
      active principles tested. The results of this study provide evidence that the
      common commercially available anthelmintic are not assuring effective chemical
      control of gastrointestinal parasitic infections in ovine flocks in the southern
      region of Rio Grande do Sul. Monepantel, the newest introduced drug in the
      Brazilian market was not effective in 18% of the flocks tested, confirming that
      the parasitic resistance can be established quickly after the introduction of new
      molecules mainly when alternative program of parasite control is not performed.

PMID- 29069159
TI  - Digenea parasites of Acestrorhynchus falcirostris (Osteichthyes,
      Acestrorhynchidae) in the state of Amazonas, Brazil.
AB  - This study presents the helminthofauna of digenean parasites of Acestrorhynchus
      falcirostris in the state of Amazonas (Brazil). Eight species belonging to four
      families were recovered: Metacercariae of Austrodiplostomum compactum
      (Diplostomidae) and Clinostomum marginatum (Clinostomidae) and mature specimens
      of Bellumcorpus majus, Prosorhynchoides carvajali, Rhipidocotyle santanaensis
      (Bucephalidae); Prosthenhystera obesa (Callodistomidae); Genarchella genarchella
      (Derogenidae) and Phyllodistomum spatula (Gorgoderidae). Examining specimens
      belonging to the genus Bellumcorpus collected from A. falcirostris, were observed
      a great variation in the size and shape of testes, which also could be observed
      in the type specimens of Bellumcorpus majus and B. schubarti. Considering the
      similar morphology and morphometric characteristics of both species, in this
      paper B. schubarti is considered synonym of B. majus. Acestrorhynchus
      falcirostris is a new host records for all these species of digenean, except to
      A. compactum and C. marginatum. Prosorhynchoides carvajali is referred for the
      first time in Brazil.

PMID- 29069160
TI  - Litomosoides silvai (Nematoda: Onchocercidae) parasitizing Akodon montensis
      (Rodentia: Cricetidae) in the southern region of Brazil.
AB  - In the present study, Litomosoides silvai parasitizing Akodon montensis in the
      southern region of Brazil is reported for the first time. New morphological
      information is provided for some structures of this nematode species, such as a
      flattened cephalic extremity, presence of two dorsal cephalic papillae, female
      tail with a constriction at its tip, "s" shaped vagina, spicules characteristic
      of the carinii species group and microfilaria tail constricted at the tip. This
      nematode was found parasitizing the thoracic cavity with a prevalence of 10%
      (2/20), mean intensity of 4 (6/2), mean abundance of 0.4 (8/20) and range of
      infection of 2-6 specimens per host, in southern Brazil. This occurrence of L.
      silvai in A. montensis is a new geographical record for southern Brazil, in the
      Upper Parana Atlantic Forest ecoregion of the northwestern region of Rio Grande
      do Sul, which is part of the Atlantic Forest biome.

PMID- 29069161
TI  - Pouteria torta: a native species of the Brazilian Cerrado as a bioindicator of
      glyphosate action.
AB  - In Brazil, the expansion of agricultural activity and the associated
      indiscriminate use of herbicides such as glyphosate is directly related to the
      loss of biodiversity in the Cerrado. The identification of plant species as
      bioindicators of herbicide action, especially species native to the area, can
      help in monitoring the impacts of xenobiotics in the remaining Cerrado. Thus,
      this study was designed to evaluate the possible use of the native Cerrado
      species Pouteria torta as a bioindicator of glyphosate action via changes in
      physiological performance. At 16 months after sowing, the effect of glyphosate
      was evaluated by applying the following doses: 0 (control), 25, 50, 100, 200,
      400, 800, and 1200 g a.e. ha-1. In response to glyphosate, P. torta exhibited
      reductions in photosynthesis and chloroplastid pigment content, as well as
      accumulation of shikimic acid and the occurrence of chlorosis and necrosis. These
      changes demonstrate the high sensitivity of P. torta to glyphosate and its
      potential for use as a bioindicator of this herbicide.

PMID- 29069162
TI  - An overview of the applicability of functional diversity in Biological
      Conservation.
AB  - Functional diversity is increasingly pointed as a useful approach to reach
      Biological Conservation goals. Here, we provide an overview of the functional
      diversity approach status in the Biological Conservation field. We sought for
      peer-reviewed papers published over a period of twenty years (from 1994 to 2014).
      First we used the general topic "functional diversity" and then refined our
      search using the key-word "conservation". We have identified the conservation
      strategies addressed, the organism studied, and the continent of study site in
      each paper. Thirteen classes of conservation strategies were identified. Plants
      were the most commonly studied organism group and most study-sites were located
      in Europe. The functional diversity approach was introduced in the Biological
      Conservation field in the early 2000's and its inclusion in conservation
      strategies is broadly advised. However, the number of papers that operationalise
      such inclusion by developing models and systems is still low. Functional
      diversity responds differently and eventually better than other measures to
      changes in land use and management, which suggests that this approach can
      potentially better predict the impacts. More studies are needed to corroborate
      this hypothesis. We pointed out knowledge gaps regarding identification of the
      responses for functional diversity about urban impacts and in research on the
      level of management intensity of land needed to maintain functional diversity. We
      recommend the use of functional diversity measures to find ecological indicators.
      Future studies should focus on the development of functional diversity measures
      of other taxa beyond plants as well as test hypothesis in tropical ecosystems.

PMID- 29069163
TI  - Effects of food availability and habitat features on the Ephemeroptera species
      composition at seasonal and spatial scales from neotropical floodplain rivers.
AB  - Brazilian floodplains have suffered great changes in their natural
      characteristics in recent decades, mainly in the flood pulse. The Upper Parana
      River floodplain is one of the few places where are found remained areas in which
      such peculiar characteristics keep reflecting on its high biodiversity.
      Ephemeroptera nymphs are one of the higher density groups among benthic
      community, occurring in many water bodies like large rivers and secondary
      channels. We sought to understand which factors are needed for the species
      establishment and how much important is the species colonization, especially in
      environments with anthropogenic changes. The marginal areas, which are more
      structured with presence of macrophytes, showed the highest density and richness
      even in the Parana River that has great human impact. We verified dominance of
      Americabaetis alphus, Tricorythopsis araponga, Tricorythopsis artigas on the
      Parana River, correlated with transparency, depth and electric conductivity,
      while the dominance of Traverella sp. was correlated with water temperature,
      especially in marginal areas. Consequently, the increasing transparency and
      electric conductivity due to the Porto Primavera dam in Parana River can be
      favoring those Ephemeroptera species. We demonstrated the importance of
      preserving the wetlands of Ivinhema River State Park mainly for Guajirolus sp.,
      which was only registered in this region. Therefore, our study provides support
      for understanding gaps from previously studies using artificial substrates in
      three large rivers which are of great importance to the upper Parana River
      floodplain.

PMID- 29069164
TI  - Potential of microalgae in the bioremediation of water with chloride content.
AB  - In this work it was carried out the bioremediation of water containing chlorides
      with native microalgae (MCA) provided by the Centre for study and research in
      biotechnology (CIBIOT) at Universidad Pontificia Bolivariana. Microalgae
      presented an adaptation to the water and so the conditions evaluated reaching a
      production of CO2 in mg L-1 of 53.0, 26.6, 56.0, 16.0 and 30.0 and chloride
      removal efficiencies of 16.37, 26.03, 40.04, 25.96 and 20.25% for microalgae1,
      microalgae2, microalgae3, microalgae4 and microalgae5 respectively. Water
      bioremediation process was carried out with content of chlorides in fed batch
      system with an initial concentration of chlorides of 20585 mg L-1 every 2 days.
      The Manipulated variables were: the flow of MCA3 (10% inoculum) for test one; NPK
      flow for test two, and flow of flow of MCA3+0.5 g L-1 NPK. Chloride removal
      efficiencies were 66.88%, 63.41% and 66.98% for test one, two and three
      respectively, for a total bioprocess time of 55 days.

PMID- 29069165
TI  - Impact of replacing fish meal by a mixture of different plant protein sources on
      the growth performance in Nile Tilapia (Oreochromis niloticus L.) diets.
AB  - The present study aimed to assess the appropriate level of replacement of fish
      meal (FM) with alternative plant sources in the feed fed to Oreochromis niloticus
      to evaluate the growth performance. Three isoproteinious (40% crude protein)
      diets were prepared from different ingredients viz., fish meal, corn gluten meal,
      wheat gluten meal, and bagasse kenna meal. O. niloticus showed a maximum increase
      in weight as 9.70, 11.09, 8.53 and 8.32 g during the 2nd, 2nd, 3rd and 2nd
      fortnight with feeding treatment A, B, C and D, respectively. The growth
      performance of the fish in terms of weight gain, specific growth rate, feed
      conversion ratio and protein efficiency ratio were found to be significantly (P <
      0.05) higher in the fish fed with 20% replacement of fishmeal in diet B. The
      worst growth performance was observed in fish fed with commercial diet,
      designated as diet D. It was concluded that the fish meal can be replaced up to
      20 percent with other plant protein sources without any negative impact on fish
      health. The replacement of fish meal with local plant sources (corn gluten meal,
      wheat gluten meal, soybean meal and bagasse kenna mix) will not only be
      beneficial to achieve better growth performance in O. niloticus, it will be a
      value addition as well.

PMID- 29069166
TI  - Implications of using the Hearing Aids on quality of life of elderly.
AB  - PURPOSE: To evaluate through standardized questionnaires the quality of life of
      elderly people with hearing loss diagnosed with and without the use of hearing
      aids (HA) and elderly without hearing complaints. METHODS: This is a cross
      sectional study with non probabilistic sample, divided into three groups divided
      as follows: 30 elderly people with diagnosed hearing loss and indication for use
      of individual sound amplification devices (hearing aids), but have not yet made
      use of the prosthesis; 30 individuals with hearing impairment who used hearing
      aids and 30 elderly without hearing complaints. Participants completed a
      questionnaire investigating sociodemographic and family data, the Hearing
      Handicap Inventory for the Elderly Screening Version (HHIE-S) and the World
      Health Organization Quality of Life - Short version (WHOQOL-BREF). In addition to
      the descriptive analysis of the data were performed tests to compare the three
      groups by applying analysis of variance (ANOVA) and the Bonferroni post hoc test.
      RESULTS: The three groups differed significantly in all domains of quality of
      life. The group of the elderly people with hearing loss diagnosed and with
      indication for the use of hearing aids presented lower scores and the group of
      the elderly with hearing disabilities that used the hearing aid and that the
      reference group. The AASI group presented the best quality of life results.
      CONCLUSION: The hearing loss affects the quality of life of the elderly. The
      effective use of hearing aid is beneficial to this population, improving their
      living and health conditions.

PMID- 29069167
TI  - Epidemiology and Health Services: history, achievements, and future.

PMID- 29069168
TI  - Epidemiology and Health Services: 25 years in review.
AB  - In 2017, Epidemiology and Health Services: journal of the Brazilian National
      Health System (RESS) celebrates 25 years. RESS was created in 1992 as SUS
      Epidemiological Report (IESUS) and, in 2003, adopted its current name and format.
      This study's objectives are to describe the subjects covered and the geographical
      spread of authors' institutions of the articles published in IESUS and RESS; and
      to map RESS' editorial policies and strategies in the following areas of focus:
      education, information, communication, co-responsibility and anticipation. The
      comparison between IESUS (1992-2002) and RESS (2003-2016) periods revealed an
      increase in the number of documents published, as well as an increase in the
      topics covered, the geographical spread of the authors and the scope of
      publication. The mapping of editorial policies and strategies has evidenced a
      large number of initiatives aligned with the principles of publication ethics,
      which may have contributed to the development of the journal.

PMID- 29069169
TI  - Use of health services among adults living in Manaus Metropolitan Region, Brazil:
      population-based survey, 2015.
AB  - OBJECTIVE: to describe the use of health services in adults living in Manaus
      Metropolitan Region, Amazonas, Brazil. METHODS: a population-based cross
      sectional study was carried out with adults (>=18 years) living in Manaus
      Metropolitan Region in 2015; probabilistic sampling with three-stage clusters was
      used; data were collected at the participants' households. RESULTS: 4,001 adults
      participated, 52.8% were women, 49.7% aged 18-34 years; 80% rated their health
      status as good/regular; in the fortnight previous to the survey, 20.9% (95%CI
      19.7;22.2%) had used a health service, 44.4% of those visited a primary health
      care unit; 2.9% (95%CI 2.4;3.4%) never used a health service; among those who
      already visited a doctor (n=3,886), most gave positive feedback about the last
      visit. CONCLUSION: health situation and last medical visit were positively
      assessed; one fifth of the population had used a health service in the two weeks
      prior to the interview, primary health care units were the main services used.

PMID- 29069170
TI  - Surveillance in Health: the social right to health promotion and protection.

PMID- 29069171
TI  - Brazilian Health Surveillance: reflections and contribution to the debate of the
      First National Conference on Health Surveillance.
AB  - This is a research on the challenges of Health Surveillance, considering its
      theories and practices. We performed a comprehensive review of international and
      national literature and institutional documents. Some of the authors also
      participated in the formulation of the guideline document prepared by the
      Formulation and Reporting Committee of the First National Conference on Health
      Surveillance. The complex Brazilian reality imposes that Health Surveillance be
      guided in a universal, integrated, participatory and territorial manner, where
      society and SUS workers play a leading role. It points out the need to design a
      structured surveillance system based on the dynamics of production, consumption
      and ways of living of the communities. The National Health Surveillance Policy
      should harbor in its core the categories and values of health social
      determination, the State's health regulatory responsibility, integrality,
      territory, participation of society and right to information.

PMID- 29069172
TI  - Can Health Surveillance be emancipatory? An alternative way of thinking about
      alternatives in times of crisis.
AB  - This article in essay form is an invitation to reflect upon the emancipatory
      character of health surveillance, a debate that was interrupted in the 1990s. In
      these times of grave political and institutional crisis in Brazil and in the year
      of the first National Conference on Health Surveillance (1a CNVS, acronym in
      Portuguese), it is particularly appropriate to revive the critical theoretical
      and epistemological discussions that have grounded the trajectory of Latin
      American social medicine and public health over the last 40 years. To this end, I
      draw on aspects of critical thinking on modernity devised by the Portuguese
      sociologist Boaventura de Sousa Santos, who postulates three pillars of
      domination: capitalism, colonialism (or coloniality), and patriarchy. In the
      current context of a crisis of civilization, rethinking emancipation requires us
      to refresh our understanding of the meaning of social struggles in terms of their
      relationship with the knowledges and epistemologies undermined by modern
      civilization and still present in the Global South, whether in spaces occupied by
      indigenous peoples and poor farmers or in urban peripheries.

PMID- 29069173
TI  - Solidarity: an innovative perspective in the management and organization of
      Sanitary Surveillance actions.
AB  - This is a theoretical essay about the development of the concept of solidarity, a
      word used in the regulatory framework and in political proposals to reorient the
      Brazilian Unified Health System (SUS). The methodology consisted of mapping
      authors addressing human action aspects related to this theme from Durkheim's
      tradition, linking them to his followers, like Marcel Mauss and authors from the
      "anti-utilitarianism" movement in social sciences. Solidarity is one way to
      express a "gift" and appears as a multidimensional action, where duty and
      freedom, instrumental interest and disinterest interpose and interlace. The
      planning and execution of sanitary surveillance (VISA) actions requires
      comprehension of organizational forms and solidary relationship management among
      agents involved in health risk control, transcending the strongly normative
      aspect of the prevailing supervision actions. The development of associative
      actions involving sanitary surveillance professionals, economic agents and
      consumers, aiming to share the responsibilities in the health risk control of
      products, services and environments subjected to Sanitary Surveillance action is
      suggested.

PMID- 29069174
TI  - The 'locus' of health oversight in Brazil's Unified Health System - a place
      between the knowledge and the practices of social mobilization.
AB  - Supervision of a health system presupposes keeping an attentive eye on the health
      situation of populations, so as to understand health, illness and healthcare as
      indissociable manifestations of human existence. Taking this point of view, this
      article examines health practices from the basis of some of their processes of
      communication. These are markedly professional-centered in their logic, with
      their emphasis on scientific, vertical and authoritarian discourse, predominantly
      in the spaces of the Unified Health System (SUS). In the territory, the process
      of communication is determinant. As a result of social interaction in daily life,
      the communication process reterritorializes the elements of the social totality:
      people, companies, institutions are re-dimensioned in the logic. It is a
      characteristic space for activities that aim for a more horizontal and democratic
      flow of communication.

PMID- 29069175
TI  - Possible ways for Public Health Surveillance practices evaluation.
AB  - This is an evaluative and qualitative study that proposes to investigate self
      assessment evaluation as a device to analyze Health Surveillance practices
      through a questionnaire built by researchers, adapted from the Self-Assessment of
      Improved Access and Primary Care Quality (AMAQ) and available on the FORMSUS
      platform. Forty-one Health Surveillance workers and managers of a large
      municipality from Sao Paulo State evaluated the realms of "management",
      "teamwork" and their respective sub-realms. Two categories were created to
      analyze the results: "Management" and "Team" in dialogue with references from
      Management, Evaluation and Health Surveillance. Most "management" and "teamwork"
      sub-realms were deemed satisfactory. Self-assessment evaluation through an
      applied evaluation tool was shown to be a powerful resource for the analysis of
      Health Surveillance practices in combination with other devices adopted by the
      Unified Health System (SUS). Unlike usual evaluation processes guided by
      quantitative markers, this self-assessable evaluative process included subjects
      and enabled the possibility of incorporating a new look at itself to the way
      Health Surveillance is carried out and support future management contracts
      between workers and managers.

PMID- 29069176
TI  - Adequacy of mortality data and correction of reported deaths from the Proactive
      Search of Deaths.
AB  - The aim of this paper is to propose indicators of adequacy and to estimate
      correction factors for deaths reported to SIM. In 2014, we carried out a
      Proactive Search to capture deaths that occurred in 2012 in a sample of
      municipalities in the regions North and Northeast, and the states of Minas
      Gerais, Mato Grosso and Goias. To characterize the coverage of deaths
      information, we proposed indicators of adequacy by municipality. Correction
      factors were estimated for individuals one year of age or older and younger than
      1 year old. Among the deaths of people aged one year or more, the coverage was
      above 90% in 12 states. As for infant deaths, the coverage was less than 80% in 7
      states. The results of the regression models showed association between the
      correction factors estimated and the proposed indicators of adequacy. We found
      very poor death information in 227 municipalities, for which the reported number
      of infant deaths even after correction, could not reach the minimum expected.
      Although the progress made in information of vital data in Brazil is recognized,
      the results show that our greatest challenge is to reach rural and remote
      municipalities, which do not yet have adequate vital information.

PMID- 29069177
TI  - Health Impact Assessment (HIA): analyses and challenges to Brazilian Health
      Surveillance.
AB  - This study aims to discuss the Health Impact Assessment (HIA), pointing out the
      main initiatives of the health sector, challenges and perspectives for its
      implementation in Brazil. HIA is a methodology recommended by the WHO and is
      widely used in several countries, but with few initiatives in Brazil. Health
      issues in the context of large projects are commonly conducted on a timely basis
      within the environmental licensing processes, unlike HIA, which proposes an
      integrated approach, with the involvement of social stakeholders in the territory
      since the beginning of the project. This is an analytical and exploratory
      research and, thus, a systematic review on the subject was carried out, as well
      as a survey of government documents on the main initiatives already conducted by
      the Ministry of Health within Environmental Health Surveillance in the
      environmental licensing processes of large projects. We sought to analyze the
      main conceptual frameworks, pointing out possibilities for their implementation
      in Brazil, as well as new perspectives for Health Surveillance in this area,
      allowing the health variable to be evaluated during several interventions of a
      policy, program or project.

PMID- 29069178
TI  - Social knowledge and the construction of drinking water preference.
AB  - The analytical categories of Health Surveillance territorialization and daily
      life guided the design of this study, which aimed to understand from the
      methodological framework of qualitative research the factors involved in the use
      of individual supply solutions (ISS) as drinking water sources. We conducted semi
      structured interviews with residents of 22 households set at a municipality in
      the Zona da Mata Mineira. Statements were fully transcribed, processed through
      content analysis and interpreted based on the psychosocial theory of social
      representations. It was possible to apprehend the social and affective components
      of social representations. The social component characterized by the
      representation of water from IWSS ISS water as clean and of good quality seemed
      to drive or justify the "resistance" of individuals to use water from public
      supply. The affective component referred to the use of IWSS water from ISS as a
      return to and protection of individuals' origins, a way to strengthen
      respondents' identity. The results pointed out that people's perceptions and
      demands might guide actions aimed to stimulate trust in the use of public system
      water and the choice of this source of supply, contributing to health protection.

PMID- 29069179
TI  - Health protection in Brazil: the National Sanitary Surveillance System.
AB  - This essay presents the singular arrangement named Health Surveillance in Brazil
      and the specificities of its components: public Health Surveillance, Worker's
      Surveillance, Environmental Surveillance, Sanitary Surveillance, as well as the
      constitutional determination to carry out the actions of sanitary and
      epidemiological surveillance and Worker's Surveillance. The two national systems
      of protection and promote health are also presented - National Public Health
      Surveillance System and National Sanitary Surveillance System, with an emphasis
      on the regulatory issues in health made by the latter and some constraints to its
      action by the Legislative Branch. It reaffirms the Brazilian State's
      constitutional duty to protect health, and to provide the means for adequate
      functioning of the two systems, bearing in mind that defense of the public
      interest in health products and services means confronting oligopolies of
      transnational economic interests. This paper states the opinion that the
      financial constraints facing the Brazilian State from time to time cannot be
      allowed to prevail over the rights of citizenship, independently of the public
      underfunding of health in Brazil.

PMID- 29069180
TI  - Work-related Mental Health Surveillance in Brazil: characteristics, difficulties,
      and challenges.
AB  - This paper addresses the challenges and difficulties in Work-related Mental
      Health (WMH) Surveillance in Brazil, based on a review of the bibliographic
      literature. From the compilation of identified academic research, it seeks to
      foster reflections about the current landscape of surveillance actions, its main
      obstacles, and possibilities for improvement. A survey of national publications
      was carried out using Scielo, Lilacs and PUBMED databases from 2002 until 2017.
      Systematizing the results allows us to group the following themes: Epidemiology
      of WMH in Brazil; Policies for WMH and VISAT; Work Environment for Mental Health;
      and, Actions and Interventions in the VISAT and WMH. The surveillance actions are
      still in the early stages; however, there is an effort to strengthen the RENAST,
      materialized in the creation of protocols and the promotion of national meetings
      which reflect the construction of a new surveillance model for worker health. We
      noted a search for new conceptual models of mental illness, a redefinition of the
      focus of care, and of intervention approaches highlighting the active role of
      workers, who are essential players in facing the challenges in this area.

PMID- 29069181
TI  - Postmarketing surveillance in Brazil: vascular catheters - an overview of
      notifications of adverse events and technical complaints.
AB  - This article identifies, quantifies and categorizes adverse event notifications
      and technical complaints related to the use of vascular catheters, received by
      the Notivisa system in the period from January 2007 to June 2016. It is a
      descriptive, retrospective, documental study with a quantitative approach. Data
      requested and supplied by Anvisa were analyzed and presented in the form of
      charts and tables. The study covered 4,682 notifications of technical complaints,
      and 671 adverse events. There was a progressive increase in notifications during
      the period studied. As to the type of technical complaint, the majority referred
      to 'suspected quality failings', the largest component being due to 'catheter
      rupture during procedure'. The adverse event most notified was 'catheter broke in
      the vein and migrated to another part of the body'. In the period studied there
      were four notifications of deaths, the most severe level of adverse event. The
      study made it possible to visualize the importance of after-sales surveillance of
      vascular catheters, as well as supplying a wide-ranging overview of their use.
      Provision of this overview could support technical surveillance activities and
      serve as input for public policies relating to this product.

PMID- 29069182
TI  - Participatory methodology as an instrument for the territorialization of
      Environmental Surveillance actions.
AB  - This paper aims to show a health territorialization methodology built from the
      experiences of endemic control and environmental health agents in the
      Metropolitan Region of Recife (RMR). Ten workshops were held with the
      participation of three hundred Health Surveillance agents and supervisors working
      in four municipalities of the RMR. Techniques such as the application of
      questionnaires, interviews and directed discussions were used. Results indicate
      that the incorporation of geographical concepts to consolidate Health
      Surveillance field actions is incipient. The territory is predominantly adopted
      from an administrative perspective, and territorialization is used as a simple
      territorial division for the development of actions. However, there is an
      understanding and consensus of the need to understand the geographic knowledge, a
      fact that was expressed by the rich collective construction of a participatory
      territorialization model that should involve a range of social stakeholders. We
      concluded that, in practice, surveillance agents have significant abilities to
      participate in the territorial management and territorialization process, not
      only collecting data, but also mainly intervening for the collective well-being.

PMID- 29069183
TI  - Presence of pesticides in atmosphere and risk to human health: a discussion for
      the Environmental Surveillance.
AB  - Brazil is the main consumer of pesticides in the world. Large-scale use of these
      products is likely to contaminate major environmental compartments and expose
      more people to their toxic effects. Therefore, this literature review was carried
      out to seek supporting elements for a qualified discussion about the performance
      of Environmental Surveillance (HS) within the Brazilian Unified Health System
      (SUS) related to air contamination by pesticides and health risks. Twelve papers
      were selected and analyzed in this literature review. Of these, only one was
      published in a specialized public health journal. Notwithstanding this, two
      epidemiological studies published in the field of environmental sciences
      investigated the association between air contaminated by pesticides and specific
      outcomes such as non-Hodgkin's lymphoma (NHL) and amyotrophic lateral sclerosis
      (ALS). Our findings reflect the lack of studies addressing such issue by public
      health. The discussion on air contamination by pesticides and potential risks to
      human health should be expanded by Brazilian science in order to further increase
      knowledge on the subject and support the HS performance capacity.

PMID- 29069184
TI  - Spatial distribution of pesticide use in Brazil: a strategy for Health
      Surveillance.
AB  - The intensive use of pesticides in Brazilian agriculture is a public health issue
      due to contamination of the environment, food and human health poisoning. The
      study aimed to show the spatial distribution of the planted area of agricultural
      crops, the use of pesticides and related health problems, as a Health
      Surveillance strategy. We obtained data from the planted area of 21 predominant
      crops, indicators of the consumption of pesticides per hectare for each crop and
      health problems. The amount of pesticides used in the Brazilian municipalities
      was spatially distributed and correlated with the incidence of pesticides
      poisoning: acute, sub-acute and chronic. There was a predominance of soybean,
      corn and sugar cane crops, which together accounted for 76% of the area planted
      in Brazil in 2015. Some 899 million liters of pesticides were sprayed in these
      crops, and Mato Grosso, Parana and Rio Grande Sul used the largest quantities,
      respectively. The health problems showed positive and significant correlations
      with pesticide use. The methodological strategy facilitated the identification of
      priority municipalities for Health Surveillance and the development of
      intersectoral actions to prevent and mitigate the impacts of pesticides on health
      and the environment.

PMID- 29069185
TI  - Federal financing of health surveillance in Brazil from 2005 to 2012: an analysis
      of distribution of resources.
AB  - Health Surveillance carries out a set of actions to prevent health risks related
      to the consumption of products and the provision of services under the Unified
      Health System (SUS). The implementation of Health Surveillance actions relies
      heavily on the federal funding policy, which induces its decentralization. This
      text aims to analyze the federal funding of Health Surveillance to States and
      Municipalities from the scheduled onlendings in the period 2005-2012. Among the
      main results are the increase of per capita values, steady at around the mean
      value of R$ 1.25/inhabitant/year; the increased number of municipalities that
      agreed to carry out strategic actions; and a stable trend in the proportions of
      each federated entity at around 50% to Municipalities, 25% to state federated
      entities and 20% to the Central Public Health Laboratories (LACENs). Results show
      that the adoption of unified nationwide per capita values caused distortions that
      indicate inequity among state territories, pointing to the need to clarify the
      concept of equity in financing under the National Health Surveillance System and
      to broaden the discussion on the currently used allocation criteria.

PMID- 29069186
TI  - Evaluation of data quality, timeliness and acceptability of the tuberculosis
      surveillance system in Brazil's micro-regions.
AB  - This study aimed to evaluate quality, acceptability and timeliness of the data in
      the tuberculosis surveillance system in Brazilian micro-regions. An ecological
      cross-sectional study was carried out, after a qualitative stage for selecting
      indicators. All 558 Brazilian micro-regions were used as units of analysis. Data
      available in the National Notifiable Diseases Information System (SINAN), from
      2012 to 2014, were used to calculate 14 indicators relating to four attributes:
      completeness, consistency, timeliness and acceptability. The study made use of
      cluster analysis to group micro-regions according to acceptability and
      timeliness. Three clusters were identified among the 473 micro-regions with
      optimal or regular completeness (70% to 100%) and with over five notifications.
      Cluster 1 (n = 109) presented mean timeliness of notification and treatment equal
      to 62.8% and 24.9%, respectively. Cluster 2 (n = 143) had a mean percentage of
      cases tested for HIV equal to 55.9%. Cluster 3 (n = 221) had the best performing
      tuberculosis indicators. Results suggest priority areas for improving
      surveillance of tuberculosis, predominantly in the central-north part of the
      country. They also point to the need to increase the timeliness of treatment and
      the percentage of cases tested for HIV.

PMID- 29069187
TI  - Analysis of individuals with leukemia: cancer surveillance system limitations.
AB  - Cancer is the second leading cause of death in the world with great impact on
      public health and leukemia is a hematological cancer directly related to
      different exposures at work. This study aimed to describe the occupational
      profile of individuals diagnosed with leukemia. This is a cross-sectional study
      of cases registered between 2007 and 2011 in the Integrador RHC database.
      Individuals from 26 Brazilian states, aged 20 years or older, were included. Of
      the 7,807 cases of leukemia, Minas Gerais recorded the highest occurrence
      (1,351). Only 52% of the cases had information on occupation. Occupations with
      the greatest number of cases of leukemia were agricultural, forestry and fishing
      workers; services, stores and markets vendors; and workers in the production of
      industrial goods and services. These occupations are exposed to substances
      considered by literature as carcinogenic agents to humans. There was a high
      underreporting of occupational data, compromising the quality of information and,
      therefore, the effectiveness of the Brazilian health surveillance system. The RHC
      also does not provide information about the agent used during the working day,
      the exposure time during working life and data from previous occupations.

PMID- 29069188
TI  - Use of genetically modified crops and pesticides in Brazil: growing hazards.
AB  - Genetically modified (GM) crops were officially authorized in Brazil in 2003. In
      this documentary study, we aimed to identify possible changes in the patterns of
      pesticide use after the adoption of this technology over a span of 13 years (2000
      to 2012). The following variables were analyzed: Pesticide use (kg), Pesticide
      use per capita (kg/inhab), Pesticide and herbicide use per area (kg/ha) and
      productivity (kg/ha). Contrary to the initial expectations of decreasing
      pesticide use following the adoption of GM crops, overall pesticide use in Brazil
      increased 1.6-fold between the years 2000 and 2012. During the same period,
      pesticide use for soybean increased 3-fold. This study shows that the adoption of
      GM crops in Brazil has led to an increase in pesticide use with possible
      increases in environmental and human exposure and associated negative impacts.

PMID- 29069189
TI  - Nutritional status of children under 5 years of age in Brazil: evidence of
      nutritional epidemiological polarisation.
AB  - The objective of this study was to evaluate the nutritional status of children
      under 5 years of age in Brazil in 2009 and its association with social and
      demographic factors. Data from the Household Budget Survey (Pesquisa de Orcamento
      Familiar - POF 2008-2009) were used, in which the nutritional profile was
      evaluated according to the weight-for-age (W/A), height-for-age (H/A) and weight
      for-height (W/H) indices (n = 14,569). The association was estimated by applying
      the Pearson association test, a logistic regression and a correspondence
      analysis. The correspondence analysis showed a higher association of thinness
      with children in the North and Northeast regions, in families with lower levels
      of income and in those of black colour/race. Overweight and obesity had a
      stronger relationship with children living in the South, Southeast and Central
      West, in males, in those from urban areas, in those of Caucasian colour/race, in
      those aged 3 years and in those from families with intermediate income ranges.
      Overweight and obesity showed a heterogeneous spatial distribution amongst
      Brazilian states. A nutritional epidemiological polarisation that presents a
      major challenge for public health is indicated: we must reduce nutritional
      deficiencies and promote healthy eating habits from childhood to improve the
      nutritional and epidemiological profiles and mortality of the population.

PMID- 29069190
TI  - Moderate and severe household food insecurity in families of people living with
      HIV/Aids: scale validation and associated factors.
AB  - Vulnerable population groups, including people living with HIV/Aids (PLHA), may
      have a high prevalence of food insecurity (FI). A cross-sectional study evaluated
      the internal validity of the Brazilian Food Insecurity Scale (Escala Brasileira
      de Inseguranca Alimentar - EBIA) and measured the prevalence of FI in a sample of
      796 PLHA in Joao Pessoa, Paraiba State (PB). The validation was performed using a
      Rasch analysis. The association of FI with sociodemographic and clinical
      characteristics was assessed using the chi-square test. Associated variables were
      included in a Poisson multiple regression model. The EBIA was valid for PLHA with
      fit values within the expected limits and item severity conforming to the
      theoretical model. The EBIA identified 66.5% of PLHA with FI in the sample (30.8%
      mild FI, 18.1% moderate FI and 17.6% severe FI). Moderate FI and severe FI were
      associated with an age younger than 43 years (prevalence ratio (PR) = 1.49; 95%
      confidence interval (CI): 1.14-1.86), primary education (PR=1.64; 95% CI: 1.24
      2.17), income per capita lower than 1/2 minimum wage (MW) (PR=1.83; 95% CI: 1.37
      2.44), lack of occupation (PR=1.59; 95% CI: 1.16-2.19) and adult-only households
      with a female reference person (PR=2.19; 95% CI: 1.45-3.31). The PLHA in this
      study had a high prevalence of FI, worsening their living conditions and
      potentially exacerbating their health problems.

PMID- 29069191
TI  - Three decades of hospital epidemiology and the challenge of integrating Health
      Surveillance: reflections from a case study.
AB  - This study proposes a reflection on the uses and future prospects of hospital
      based health surveillance based on the account of a pioneering experience in
      hospital epidemiology, the epidemiology service at the Hospital Federal dos
      Servidores do Estado - HFSE, which served as the basis for the creation of
      epidemiologic surveillance units in municipal and state hospitals in Rio de
      Janeiro, Brazil. The epidemiology service has combined epidemiological
      surveillance, continuing education, in-service training, research, and health
      service evaluation since 1986. The service is part of the national
      epidemiological surveillance network and was responsible for the notification of
      55,747 cases between 1986 and 2016, most of which were the result of active
      search. The integration of various levels of health surveillance and health care
      makes classical control activities more agile and provides instruments for
      measuring. The important role played by the service in human resources training
      is evident in the training of 1,835 medical interns and 78 residents up to 2016.
      In addition, this experience has served as the basis for the implantation of
      several other hospital epidemiological surveillance units. Current challenges
      include the promotion of effective communication and coordination among the other
      health surveillance committees.

PMID- 29069192
TI  - Medicine poisoning mortality trend by gender and age group, Sao Paulo State,
      Brazil, 1996-2012.
AB  - This study looked into mortality due to medicinal drug poisoning by age, gender
      and intent among the population of the state of Sao Paulo. The adjusted time
      sequence of mortality due to drug poisoning was developed based on data available
      in the DATASUS Mortality Data System for 1996 to 2012. We checked the variables
      for magnitude and trends. We found an increase in adjusted mortality starting in
      2005, and more so as of 2009, confirmed by a 95% CI for the average annual rate
      of change. (AARC) We did not find the same trend in overall mortality in the
      state (AARC = -0.22%, 95% CI = -1.12 - 0.69) for specific, external cause
      mortality (AARC = -3.14%, 95% CI = -4.75 - -1.49) and for mortality due to
      accidental drug poisoning (AARC=+9,76%, 95% IC = -12.16 - 37.14). The largest
      increase was found in intentional self-poisoning with medicinal drugs (AARC =
      +10.64%, 95% CI = 6.92 - 14.40), and among the younger subjects (largest
      magnitude). The trend in mortality due to drug poisoning in the State of Sao
      Paulo, the importance of intent and mortality among the younger population
      reiterate the need to implement control measures.

PMID- 29069193
TI  - Surveillance of occupational accidents by sentinel workers' health centers in the
      municipality of Fortaleza, Northeast of Brazil.
AB  - This article examines the factors associated with the notification of
      occupational accidents by sentinel workers' health centers in the municipality of
      Fortaleza in the northeast of Brazil. An analytical cross-sectional study was
      conducted of five sentinel workers' health centers for serious and fatal
      occupational accidents. A total of 354 interviews were conducted with
      professionals responsible for notifying occupational accidents. Bivariate
      analysis was conducted using Pearson's chi-square test and/or Fisher's exact test
      using prevalence ratios and 95% confidence intervals, followed by stratified
      analysis and multivariate Poisson regression adopting the stepwise forward
      method. Variables that obtained a p-value of less than or equal to the chosen
      significance level (0.05) were maintained in the final model. Professionals who
      had a greater number of years of work experience, had undertaken three training
      courses, had knowledge of policy directives concerning occupational accidents,
      were familiar with the SINAN notification form, were aware that occupational
      accidents are reportable, and discussed the theme of occupational accidents in
      the workplace were statistically more likely to notify occupational accidents.
      Education and training helps raise awareness among health professionals.

PMID- 29069194
TI  - Worker's Surveillance in the Primary Care: learning with Family Health team of
      Joao Pessoa, Paraiba, Brazil.
AB  - This study analyzed the Worker's Surveillance activities of Family Health teams,
      based on the perceptions of physicians and nurses in the city of Joao Pessoa. We
      used a 30-question questionnaire split into four blocks: data on the
      professional, occupational healthcare practices focusing on the production and
      epidemiological profile, and matrix and institutional support to the teams. A
      total of 179 professionals participated, 82% of them were female, and 46% aged 50
      or more; 60% had worked in the area for more than 10 years. Results show that
      Worker's Surveillance activities are not part of team day-to-day activities: 53%
      mapped productive activities and 30% related them to health hazards. Twenty-four
      percent mentioned activities to eliminate/mitigate exposure to risk and
      vulnerabilities. The support of Family Health teams by the Reference Center for
      Occupational Health was mentioned by 45% of the participants, less than the
      number reported for Worker's Surveillance. Involvement in occupational health
      training was mentioned by 24% of the professionals. Results suggest the need to
      expand and strengthen continued education and team support.

PMID- 29069195
TI  - A glance over the surveillance of fetal deaths of Jaboatao dos Guararapes in the
      Brazilian state of Pernambuco, Brazil, in 2014.
AB  - This study aimed to achieve a complete evaluation of the records of
      investigation, and the principal indicators of fetal death surveillance of
      Jaboatao dos Guararapes, Pernambuco State, and their contributions Mortality
      Information System (Sistema de Informacoes sobre Mortalidade - SIM). The
      population of the study comprised all fetal deaths taking place in the year 2014,
      of people resident in the town. The data were obtained from death investigation
      records and the databank of the SIM. The completeness of the report forms of 68
      fetal deaths, and 13 variables in the death certificates, before and after the
      investigation, was analyzed. In 2014 the rate of fetal mortality was 10.30/00. Of
      the 102 deaths, 86.3% (88) were investigated, and 67% (59) were investigated
      within a period of 120 days. Only nine (10.2% of the deaths investigated) were
      the subject of a final discussion to complete investigation. The Hospital Form
      was the most frequently filled in, and the Summary Form was the form most
      completely filled in. The Outpatient Form was the least well filled-in. In the
      death certificates, there were rectifications made in the 13 variables studied.
      The results showed deficiencies and operational difficulties in Fetal Death
      Surveillance in Jaboatao dos Guararapes. Conversely, the study revealed the
      contribution of the investigation process in qualifying of the SIM.

PMID- 29069196
TI  - Identification of priority Health Regions in the State of Rio Grande do Sul,
      Brazil, for Health Surveillance actions.
AB  - This paper aimed to identify the priority Health Regions of Rio Grande do Sul
      (RS) to implement Health Surveillance strengthening actions. This is a
      descriptive study with data from time series of 11 (eleven) Health Surveillance
      indicators of the Ministry of Health's 2016 Guidelines, Objectives, Targets and
      Indicators Journal agreed by the Bipartite Interagency Committee/RS. The selected
      indicators are synthesized to produce a Composite Health Surveillance Assessment
      Indicator (ICAVES) for each of the 30 Health Regions of the state, creating
      values ranging from zero (worst) to 1 (best), using the Human Development Index
      (HDI) construction calculation method. The lowest rates of the composite
      indicator are found in the Health Regions "20-Rota da Producao" and "19-Regiao do
      Botucarai". These two Health Regions are priorities for the strengthening of
      collective Health Surveillance actions and the management of health risks and
      diseases, considering horizontal equity as guideline of the Unified Health
      System.

PMID- 29069197
TI  - Evaluation of Health Surveillance in the Zona da Mata Mineira: from standards to
      practice.
AB  - Health Surveillance is of paramount importance when confronted with the current
      Brazilian epidemiological setting. This study aims to evaluate the level of
      Health Surveillance in the Zona da Mata Mineira region. This is an evaluative
      study, and data were collected in the first half of 2016. The research universe
      consisted of seven municipalities in the Zona da Mata Mineira complex.
      Municipalities were selected with reference to available operational
      epidemiological, environmental and sanitary surveillance. The subjects under
      analysis were the Surveillance coordinators (n = 21), Health Surveillance
      coordinators (n = 7) and Health secretaries (n = 7). We conducted interviews
      using a semi-structured and elaborated questionnaire based on the Donabedian
      triad: Structure, Process and Outcome. A score system was established in order to
      obtain the classification of performance, realm and sub-realms, in which a score
      was assigned for each criterion. We used incipient, intermediate or advanced
      cutoff points to classify the level of Health Surveillance of scores were below
      5.99 points, between 6.0 and 7.99 points and between 8 and 10 points,
      respectively. The level of regional Health Surveillance performance level was
      classified as an intermediate.

PMID- 29069198
TI  - Death surveillance as an indicator of the quality of health care for women and
      children.
AB  - The study aimed to evaluate the implementation of a regional death surveillance
      network, reflecting on challenges and potentialities of performance as
      observatory of violence against women. The research involved nine municipalities
      of a health region set at the Zona da Mata, Minas Gerais, Brazil. We followed the
      meetings of the regional death surveillance committee and conducted semi
      structured interviews with professional members of the committee and municipal
      health managers. Furthermore, we analyzed information concerning investigations
      conducted and, in one municipality, we analyzed the notifications of deaths and
      cases of violence against women. The results point to some difficulties: lack of
      recognition of the death surveillance activity; work overload; failure in
      communication between institutions and poor resources, infrastructure and
      professional training. There were also improvements, namely: greater interaction
      between municipalities; increased investigations and greater awareness of the
      importance of death surveillance among workers. We identified cases of domestic,
      obstetric and institutional violence through the investigation of deaths. The
      experience as a regional committee reinforces the strategy of strengthening death
      surveillance and the network of care for women in situation of violence.

PMID- 29069199
TI  - On Integrated Residency in Health with emphasis on Health Surveillance.
AB  - Taking into account the four underpinning areas of Health Surveillance
      (environmental, epidemiological, health and worker's health), the performance of
      professionals in this area requires a broad and complex set of information from
      many fields of knowledge, including that which is not classified as health.
      Considering the need to prepare professionals to work in Health Surveillance in
      the Unified Health System (SUS), integrating the four fields of knowledge, the
      Public Health School of Rio Grande do Sul (ESP/RS) and the surveillance areas of
      the municipality of Porto Alegre and Rio Grande do Sul State have established a
      new emphasis in the traditional residency of ESP/RS. This work uses the
      experience report descriptive method. It shows the activities of residents in the
      formation course of the first year, fourth class of this in-service education
      experience and takes stock of results of residency freshmen.

PMID- 29069201
TI  - Health information on the internet and dengue.

PMID- 29069200
TI  - The trajectory of Virginia Schall: integration of Health, Education, Science and
      Literature.
AB  - This article presents Virginia Schall's professional career, interrupted very
      early. It highlights her major role in the integration of the fields of Health,
      Education and Scientific Dissemination in Brazil. The contextualization of her
      academic and literary production as a researcher at the Oswaldo Cruz Foundation,
      demonstrates Virginia's contribution in strengthening the institution and in the
      teaching of dozens of researchers and students. With a strong inter- and
      multidisciplinary approach, she was a pioneer in the field of Health Education,
      Science Education, and Science Dissemination. Virginia participated in the
      implementation of two post graduate courses and regularly worked as consultant
      for CNPq, CAPES, SVS/MS and the Ministry of Education, consolidating national
      policies in these areas. Besides being the author of several children's books and
      educational resources about health, environment and science, Virginia conceived
      the Life Museum at Fiocruz-RJ, as a space for integrating science, culture, and
      society, with focus on science, health, and technology information and education.
      She was also a poet, member of the Women's Academy of Letters in Minas Gerais,
      and produced diverse and award-winning poetry and prose literary pieces.

PMID- 29069202
TI  - Association of Inflammation and Endothelial Dysfunction with Coronary
      Microvascular Resistance in Patients with Cardiac Syndrome X.
AB  - BACKGROUND: Although a proportion of CSX patients have impaired brachial artery
      flow-mediated dilatation (FMD) in response to hyperemia, suggesting that
      endothelial dysfunction in these patients may be systemic and not just confined
      to the coronary circulation; the underlying mechanisms triggering endothelial
      dysfunction in these patients are still incompletely understood. OBJECTIVES: To
      assess the association of the index of Microcirculatory Resistance (IMR) with
      endothelial dysfunction and inflammation in patients with CSX. METHODS: We
      studied 20 CSX patients and 20 age and gender-matched control subjects.
      Thermodilution-derived coronary flow reserve (CFR) and IMR were measured using a
      pressure-temperature sensor-tipped guidewire. Brachial artery FMD was measured
      using high-resolution, two-dimensional ultrasound images obtained with a Doppler
      ultrasound device (HDI-ATL 5000, USA) with a 5 MHz to 12 MHz linear-array
      transducer. RESULTS: Compared with in control subjects, CFR was significantly
      lower (2.42 +/- 0.78 vs. 3.59 +/- 0.79, p < 0.001); IMR was higher (32.2 +/- 8.0
      vs. 19.5 +/- 5.5, p < 0.001); the concentration of hs-CRP and FMD was higher
      (4.75 +/- 1.62 vs. 2.75 +/- 1.50; 5.24 +/- 2.41 vs. 8.57 +/- 2.46, p < 0.001) in
      CSX patients. The Duke treadmill score (DTS) was correlated positively to CFR and
      FMD (0.489 and 0.661, p < 0.001), it was negative to IMR and hsCRP (-0.761 and 
      0.087, p < 0.001) in CSX patients. CONCLUSIONS: The main finding in this study is
      that the DTS measured in patients with CSX was associated to hsCRP and FMD.
      Moreover, the independent effects of exercise tolerance can significantly impair
      FMD and hsCRP in CSX patients; especially it is particularly important to whom
      where FMD was associated negatively with IMR.

PMID- 29069205
TI  - Case 5/2017 - A 28-Year-Old Woman with Cor Pulmonale Due to Pulmonary
      Hypertension Secondary to Chronic Pulmonary Thromboembolism.

PMID- 29069204
TI  - Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment
      of Obesity.
AB  - BACKGROUND: Different types of high-fat and/or high-energy diets have been used
      to induce obesity in rodents. However, few studies have reported on the effects
      observed at the initial stage of obesity induced by high-fat feeding on cardiac
      functional and structural remodelling. OBJECTIVE: To characterize the initial
      moment of obesity and investigate both metabolic and cardiac parameters. In
      addition, the role of Ca2+ handling in short-term exposure to obesity was
      verified. METHODS: Thirty-day-old male Wistar rats were randomized into two
      groups (n = 19 each): control (C; standard diet) and high-fat diet (HF,
      unsaturated high-fat diet). The initial moment of obesity was defined by weekly
      measurement of body weight (BW) complemented by adiposity index (AI). Cardiac
      remodelling was assessed by morphological, histological, echocardiographic and
      papillary muscle analysis. Ca2+ handling proteins were determined by Western
      Blot. RESULTS: The initial moment of obesity occurred at the 3rd week. Compared
      with C rats, the HF rats had higher final BW (4%), body fat (20%), AI (14.5%),
      insulin levels (39.7%), leptin (62.4%) and low-density lipoprotein cholesterol
      (15.5%) but did not exhibit alterations in systolic blood pressure.
      Echocardiographic evaluation did not show alterations in cardiac parameters. In
      the HF group, muscles were observed to increase their +dT/dt (C: 52.6 +/- 9.0
      g/mm2/s and HF: 68.0 +/- 17.0 g/mm2/s; p < 0.05). In addition, there was no
      changes in the cardiac expression of Ca2+ handling proteins. CONCLUSION: The
      initial moment of obesity promotes alterations to hormonal and lipid profiles
      without cardiac damage or changes in Ca2+ handling.

PMID- 29069203
TI  - First results of the Brazilian Registry of Percutaneous Left Atrial Appendage
      Closure.
AB  - BACKGROUND: Left atrial appendage closure (LAAC) is an effective alternative to
      oral anticoagulation (OA) for the prevention of stroke in patients with non
      valvular atrial fibrillation (NVAF). OBJECTIVE: To present the immediate results
      and late outcomes of patients submitted to LAAC and included in the Brazilian
      Registry of Percutaneous Left Atrial Appendage Closure. METHODS: 91 patients with
      NVAF, high stroke risk (CHA2DS2VASc score = 4.5 +/- 1.5) and restrictions to OAC
      (HAS-BLED score = 3.6 +/- 1.0) underwent 92 LAAC procedures using either the
      Amplatzer cardiac plug or the Watchman device in 11 centers in Brazil, between
      late 2010 and mid 2016. RESULTS: Ninety-six devices were used (1.04
      device/procedure, including an additional non-dedicated device), with a
      procedural success rate of 97.8%. Associated procedures were performed in 8.7% of
      the patients. Complete LAAC was obtained in 93.3% of the successful cases. In
      cases of incomplete closure, no residual leak was larger than 2.5 mm. One patient
      needed simultaneous implantation of 2 devices. There were 7 periprocedural major
      (5 pericardial effusions requiring pericardiocentesis, 1 non-dedicated device
      embolization and 1 coronary air embolism without sequelae) and 4 minor
      complications. After 128.6 patient-years of follow-up there were 3 deaths
      unrelated to the procedure, 2 major bleedings (one of them in a patient with an
      unsuccessful LAAC), thrombus formation over the device in 2 cases (both resolved
      after resuming OAC for 3 months) and 2 strokes (2.2%). CONCLUSIONS: In this
      multicenter, real world registry, that included patients with NVAF and high
      thromboembolic and bleeding risks, LAAC effectively prevented stroke and bleeding
      when compared to the expected rates based on CHA2DS2VASc and HASBLED scores for
      this population. Complications rate of the procedure was acceptable considering
      the beginning of the learning curve of most of the involved operators.

PMID- 29069206
TI  - G-Proteins Agonists and NO/cGMP Blockers: Unexplored Frontiers in the
      Pharmaceutical Industry.

PMID- 29069207
TI  - Myocardial Edema without Fibrosis by Magnetic Resonance T2 Mapping in Acute
      Chagas' Myocarditis.

PMID- 29069208
TI  - Childhood Obesity, MMP-9 Levels, and Vitamin D.

PMID- 29069209
TI  - Spider-Like Coronary Anatomy; the True Spider!

PMID- 29069210
TI  - Positions, Guidelines and Standardizations. Vehicles of Assistance to Medical
      Practice.

PMID- 29069211
TI  - Can the risk in public-private partnerships be classified?
AB  - In the coming years, public-private partnerships (PPPs) should play an
      increasingly relevant role as an important alternative for financing projects and
      infrastructure in public services. However, especially in public health, PPPs are
      not always a good alternative, since they may introduce distortions in the agenda
      that sets health needs, favoring companies' interests. Public agencies can
      benefit from collaboration with the private sector in areas where there is a lack
      of specialization, such as the development of research and technologies. Even in
      these cases, each institution's role needs to be defined in order to avoid
      conflicts of interest. This can be challenging when dealing with the formulation
      of public and regulatory policies, on the impacts of certain policies, especially
      in developing countries. To engage with the private sector without compromising
      the integrity of government actions requires a broad discussion by public health
      stakeholders, for clear reasons of conflicting visions and scopes between
      corporations and public health. Combined with this is the need for multi-sector
      approaches, with a high load of financial investments in the various dimensions
      of policies to control the most prevalent diseases, especially chronic non
      communicable diseases (NCD). This article classifies PPPs in categories in order
      to minimize the potential risks of conflicts of interest than can impact public
      health. These categories are defined as possible, possible with caveats, and
      impossible for involvement with certain institutions.

PMID- 29069212
TI  - Analysis of the tobacco industry's interference in the enforcement of health
      warnings on tobacco products in Brazil.
AB  - This article aims to analyze the relationship between the Brazilian government's
      adoption of a regulatory measure with a strong impact on the population and the
      opposition by invested interest groups. The methodology involves the analysis of
      official documents on the enforcement of health warnings on tobacco products sold
      in Brazil. In parallel, a search was conducted for publicly available tobacco
      industry documents resulting from lawsuits, with the aim of identifying the
      industry's reactions to this process. The findings suggest that various
      government acts were affected by direct interference from the tobacco industry.
      In some cases the interventions were explicit and in others they were indirect or
      difficult to identify. In light of the study's theoretical framework, the article
      provides original information on the Brazilian process that can be useful for
      government policymakers in the strategic identification of tobacco control
      policies.

PMID- 29069213
TI  - Institutions and the implementation of tobacco control in Brazil.
AB  - This research examines the institutional features of Brazil's National Commission
      for the Implementation of the Framework Convention on Tobacco Control (CONICQ)
      and how these institutional features have facilitated and hindered its ability to
      foster intersectoral tobacco control. In particular, we evaluate the key
      institutional features of CONICQ starting from when it was one of the key drivers
      of change and improvements in early tobacco control policies, which helped to
      make Brazil a world leader in this area. We also examine how the committee has
      evolved, as tobacco control has improved and particularly elucidate some of the
      major challenges that it faces to bring together often disparate government
      sectors to generate public health policies.

PMID- 29069214
TI  - Conceptualizing threats to tobacco control from international economic
      agreements: the Brazilian experience.
AB  - Using the results of dozens of interviews with key actors involved in tobacco
      control policymaking, we examine these actors' perceptions of threats to tobacco
      control policy efforts from international economic policies on trade and
      investment. We also evaluate, from a legal perspective, the genuine threats that
      exist or potential challenges that economic policies may pose to the Brazilian
      government's public health efforts. We find that most actors did not perceive
      these economic policies as a major threat to tobacco control. Objectively, we
      found that some threats do exist. For example, Brazil's attempt to ban most
      tobacco additives and flavorings continues to met resistance at the World Trade
      Organization.

PMID- 29069215
TI  - A timely article focus on public health risk.

PMID- 29069216
TI  - Debate on the paper by Costa e Silva et al.

PMID- 29069217
TI  - Difficulties in the classification of public-private partnerships in public
      health.

PMID- 29069218
TI  - Debate on the paper by Costa e Silva et al.

PMID- 29069219
TI  - The authors reply.

PMID- 29069220
TI  - Total phenolic, flavonoid, alkaloid and iridoid content and preventive effect of
      Lider-7-tang on lipopolysaccharide-induced acute lung injury in rats.
AB  - Lider-7-tang, a medicine used for the treatment of respiratory diseases
      especially pneumonia and fever in Mongolian Traditional Medicine, was selected
      for this phytochemical and pharmacological study. The objectives of the study
      were to determine total biological active substances and analyze the effects of
      Lider-7-tang treatment in rats with acute lung injury (ALI). Quantitative
      determination of the total active constituents (phenolic, flavonoid, iridoid and
      alkaloid) of the methanol extract of Lider-7-tang was performed using Folin
      Ciocalteu reagent, aluminum chloride reagent, Trim-Hill reagent, and Bromocresol
      green reagent, respectively. A total of fifty 8-10-week-old male Wistar rats (200
      240 g) were randomized into three groups: control group, lipopolysaccharide (LPS)
      group (7.5 mg/kg) and LPS+Lider-7 group (90 mg/kg Lider-7-tang before LPS
      administration). The total content of alkaloids was 0.2+/-0.043%, total phenols
      7.8+/-0.67%, flavonoids 3.12+/-0.206%, and iridoids 0.308+/-0.0095%. This study
      also evaluated the effects of Lider-7 on levels of inflammatory mediators by
      observing histopathological features associated with LPS-induced ALI. The rats
      pretreated with Lider-7 had significantly lower levels of IL-6 (at 3 and 6 h),
      and TNF-alpha (at 3, 6, 9, and 12 h). The current study showed that Lider-7
      exerted a preventive effect against LPS-induced ALI, which appeared to be
      mediated by inhibiting the release of pro-inflammatory cytokines.

PMID- 29069221
TI  - Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload
      injured bone marrow.
AB  - Using an iron overload mouse model, we explored the protective effect of
      deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow
      hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were
      intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to
      establish an iron overload (Fe) model. DFX or NAC were co-administered with iron
      dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was
      then examined. Iron overload markedly decreased the number of murine HSPCs in
      bone marrow. Subsequent colony-forming cell assays showed that iron overload also
      decreased the colony forming capacity of HSPCs, the effect of which could be
      reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron
      overload could be alleviated by DFX and NAC.

PMID- 29069222
TI  - Effect of a rosmarinic acid supplemented hemodialysis fluid on inflammation of
      human vascular endothelial cells.
AB  - Chronic systemic inflammation and repetitive damage of vascular endothelia by
      incompatible dialysis system are probable causes of cardiovascular disease in
      patients on dialysis. The present study aimed to assess in vitro biocompatibility
      and anti-inflammatory effect of hemodialysis fluid supplemented with rosmarinic
      acid (RA) using human umbilical vein endothelial cells (HUVEC). HUVECs (5*106
      cells/mL) were pre-exposed to 1 MUg/mL of lipopolysaccharides (LPS) and incubated
      with RA-supplemented hemodialysis fluid (HDF). Cytotoxicity was assessed
      qualitatively by morphologic assessment and quantitatively by MTT assay.
      Expressions of proinflammatory mediators were assessed using quantitative real
      time PCR and production of NO was quantified. Phosphorylation of AKT and nuclear
      localization of nuclear factor kappa B (NF-kappaB) were examined using western
      blotting. Exposure of HUVECs to RA-supplemented HDF had no influence on
      morphology and viability. Inhibition of proinflammatory mediator production in
      HUVECs by RA supplementation to HDF was significant in a dose-dependent manner.
      Exposure to RA-supplemented HDF resulted in a decrease in nitric oxide synthase
      expression and reduction of NO production in LPS-stimulated HUVECs. RA
      supplementation of HDF suppressed Akt activation in LPS-stimulated HUVECs. In
      addition, the level of cellular IkappaB was increased in parallel to a reduced
      nuclear translocation of NF-kappaB in LPS-induced endothelial cells. Our results
      suggest that RA-supplemented HDF is biocompatible and significantly suppressed
      inflammation induced in endothelial cells. In this respect, the use of HDF
      supplemented with RA could alleviate inflammation and improve long-term treatment
      of patients with renal failure on dialysis. Further clinical studies are required
      to confirm the effects.

PMID- 29069223
TI  - MicroRNA profiling identifies miR-7-5p and miR-26b-5p as differentially expressed
      in hypertensive patients with left ventricular hypertrophy.
AB  - Recent evidence suggests that cell-derived circulating miRNAs may serve as
      biomarkers of cardiovascular diseases. However, a few studies have investigated
      the potential of circulating miRNAs as biomarkers for left ventricular
      hypertrophy (LVH). In this study, we aimed to characterize the miRNA profiles
      that could distinguish hypertensive patients with LHV, hypertensive patients
      without LVH and control subjects, and identify potential miRNAs as biomarkers of
      LVH. LVH was defined by left ventricular mass indexed to body surface area >125
      g/m2 in men and >110 g/m2 in women and patients were classified as hypertensive
      when presenting a systolic blood pressure of 140 mmHg or more, or a diastolic
      blood pressure of 90 mmHg or more. We employed miRNA PCR array to screen serum
      miRNAs profiles of patients with LVH, essential hypertension and healthy
      subjects. We identified 75 differentially expressed miRNAs, including 49
      upregulated miRNAs and 26 downregulated miRNAs between LVH and control patients.
      We chose 2 miRNAs with significant differences for further testing in 59
      patients. RT-PCR analysis of serum samples confirmed that miR-7-5p and miR-26b-5p
      were upregulated in the serum of LVH hypertensive patients compared with healthy
      subjects. Our findings suggest that these miRNAs may play a role in the
      pathogenesis of hypertensive LVH and may represent novel biomarkers for this
      disease.

PMID- 29069224
TI  - Effects of a 4-week high-intensity interval training on pacing during 5-km
      running trial.
AB  - This study analyzed the influence of a 4-week high-intensity interval training on
      the pacing strategy adopted by runners during a 5-km running trial. Sixteen male
      recreational long-distance runners were randomly assigned to a control group
      (CON, n=8) or a high-intensity interval training group (HIIT, n=8). The HIIT
      group performed high-intensity interval-training twice per week, while the CON
      group maintained their regular training program. Before and after the training
      period, the runners performed an incremental exercise test to exhaustion to
      measure the onset of blood lactate accumulation, maximal oxygen uptake (VO2max),
      and peak treadmill speed (PTS). A submaximal constant-speed test to measure the
      running economy (RE) and a 5-km running trial on an outdoor track to establish
      pacing strategy and performance were also done. During the 5-km running trial,
      the rating of perceived exertion (RPE) and time to cover the 5-km trial (T5) were
      registered. After the training period, there were significant improvements in the
      HIIT group of ~7 and 5% for RE (P=0.012) and PTS (P=0.019), respectively. There
      was no significant difference between the groups for VO2max (P=0.495) or onset of
      blood lactate accumulation (P=0.101). No difference was found in the parameters
      measured during the 5-km trial before the training period between HIIT and CON
      (P>0.05). These findings suggest that 4 weeks of HIIT can improve some
      traditional physiological variables related to endurance performance (RE and
      PTS), but it does not alter the perception of effort, pacing strategy, or overall
      performance during a 5-km running trial.

PMID- 29069225
TI  - Monoterpenoids (thymol, carvacrol and S-(+)-linalool) with anesthetic activity in
      silver catfish (Rhamdia quelen): evaluation of acetylcholinesterase and GABAergic
      activity.
AB  - This study evaluated the anesthetic potential of thymol and carvacrol, and their
      influence on acetylcholinesterase (AChE) activity in the muscle and brain of
      silver catfish (Rhamdia quelen). The AChE activity of S-(+)-linalool was also
      evaluated. We subsequently assessed the effects of thymol and S-(+)-linalool on
      the GABAergic system. Fish were exposed to thymol and carvacrol (25, 50, 75, and
      100 mg/L) to evaluate time for anesthesia and recovery. Both compounds induced
      sedation at 25 mg/L and anesthesia with 50-100 mg/L. However, fish exposed to
      carvacrol presented strong muscle contractions and mortality. AChE activity was
      increased in the brain of fish at 50 mg/L carvacrol and 100 mg/L thymol, and
      decreased in the muscle at 100 mg/L carvacrol. S-(+)-linalool did not alter AChE
      activity. Anesthesia with thymol was reversed by exposure to picrotoxin (GABAA
      antagonist), similar to the positive control propofol, but was not reversed by
      flumazenil (antagonist of benzodiazepine binding site), as observed for the
      positive control diazepam. Picrotoxin did not reverse the effect of S-(+)
      linalool. Thymol exposure at 50 mg/L is more suitable than carvacrol for
      anesthesia in silver catfish, because this concentration did not cause any
      mortality or interference with AChE activity. Thymol interacted with GABAA
      receptors, but not with the GABAA/benzodiazepine site. In contrast, S-(+)
      linalool did not act in GABAA receptors in silver catfish.

PMID- 29069227
TI  - Bone mineral density and inflammatory bowel disease severity.
AB  - Inflammatory bowel disease (IBD) is associated with low bone mineral density
      (BMD). In this study, the association between disease severity and BMD in
      patients with IBD was evaluated. Associations between BMD and the Montreal
      classification, disease activity and drug therapy were also tested. A cross
      sectional prevalence study with a comparison group was conducted. One hundred and
      twenty-eight patients were evaluated: 68 patients with ulcerative colitis (UC),
      and 60 with Crohn's disease (CD). The control group consisted of 67 healthy
      subjects. All patients and controls had BMD measured and in IBD patients, current
      medications, hospitalization, and disease location, extent and phenotype,
      according to the Montreal classification, were recorded. Multiple correspondence
      analysis was applied to evaluate categorical variables. In the CD group, most
      patients were diagnosed between 17-40 years of age. Ileocolonic and non
      stricturing non-penetrating disease were the most frequent disease location and
      behavior, respectively. In UC patients, extensive colitis was the most frequent
      disease location. UC and CD patients were more likely to have osteopenia than
      controls (OR=14.93/OR=24.38, respectively). In the CD group, male patients,
      perianal disease, penetrating behavior and age at diagnosis >40 years were
      associated with low BMD. Taking azathioprine and infliximab also seemed to be
      associated with osteopenia. In the UC group, we observed an association between
      low BMD and male patients, left colitis, corticosteroid use and hospitalization.
      Disease activity was not associated with osteopenia or osteoporosis in CD and UC
      patients. Disease severity seems to be associated with osteopenia in IBD
      patients.

PMID- 29069226
TI  - Effects of Lippia sidoides essential oil, thymol, p-cymene, myrcene and
      caryophyllene on rat sciatic nerve excitability.
AB  - Lippia sidoides Cham is a typical herb species of Northeast Brazil with
      widespread use in folk medicine. The major constituents of the essential oil of
      L. sidoides (EOLs) are thymol, p-cymene, myrcene, and caryophyllene. Several
      studies have shown that the EOLs and its constituents have pharmacological
      effects, including antibacterial, anti-inflammatory, antioxidant and
      neuroprotective activity. Therefore, this work aimed to investigate the effects
      of the EOLs and their main constituents on rat sciatic nerve excitability. The
      sciatic nerves of adult Wistar rats were dissected and mounted in a moist
      chamber. Nerves were stimulated by square wave pulses, with an amplitude of 40 V,
      duration of 100 MUs to 0.2 Hz. Both EOLs and thymol inhibited compound action
      potential (CAP) in a concentration-dependent manner. Half maximal inhibitory
      concentration for CAP peak-to-peak amplitude blockade were 67.85 and 40 ug/mL for
      EOLs and thymol, respectively. CAP peak-to-peak amplitude was significantly
      reduced by concentrations >=60 ug/mL for EOLs and >=30 ug/mL for thymol. EOLs and
      thymol in the concentration of 60 ug/mL significantly increased chronaxie and
      rheobase. The conduction velocities of 1st and 2nd CAP components were also
      concentration-dependently reduced by EOLs and thymol in the range of 30-100
      ug/mL. Differently from EOLs and thymol, p-cymene, myrcene and caryophyllene did
      not reduce CAP in the higher concentrations of 10 mM. These data demonstrated
      that EOLs and thymol inhibited neuronal excitability and were promising agents
      for the development of new drugs for therapeutic use.

PMID- 29069228
TI  - Different levels of brain-derived neurotrophic factor and cortisol in healthy
      heavy smokers.
AB  - Studies suggest that brain-derived neurotrophic factor (BDNF) and the
      hypothalamic-pituitary-adrenal (HPA) axis modulate dopaminergic activity in
      response to nicotine and that the concentrations of BDNF and cortisol seem to be
      dependent on the amount and duration of smoking. Therefore, we investigated BDNF
      and cortisol levels in smokers ranked by daily cigarette consumption. Twenty
      seven adult males (13 non-smokers and 14 smokers) participated in the study. The
      smokers were divided in two groups: light (n=7) and heavy smokers (n=7).
      Anthropometric parameters and age were paired between the groups, and plasma BDNF
      and salivary cortisol levels were measured. Saliva samples were collected on
      awakening, 30 min after awakening, at 10:00 and 12:00 am, 5:00 and 10:00 pm.
      Additionally, cotinine serum levels were measured in smokers. Heavy smokers had
      higher mean values of BDNF compared to the control group (P=0.01), whereas no
      difference was observed in light smokers. Moreover, heavy smokers presented lower
      cortisol levels in the last collection (10:00 pm) than the control group (P=0.02)
      and presented statically higher values of cotinine than the light smokers
      (P=0.002). In conclusion, changes in BDNF and cortisol levels (10:00 pm) appear
      to be dependent on heavy cigarette smoking and can be involved in activation and
      in the relationship between the mesolimbic system and the HPA axis.

PMID- 29069229
TI  - Physical exercise-induced fatigue: the role of serotonergic and dopaminergic
      systems.
AB  - Brain serotonin and dopamine are neurotransmitters related to fatigue, a feeling
      that leads to reduced intensity or interruption of physical exercises, thereby
      regulating performance. The present review aims to present advances on the
      understanding of fatigue, which has recently been proposed as a defense mechanism
      instead of a "physiological failure" in the context of prolonged (aerobic)
      exercises. We also present recent advances on the association between serotonin,
      dopamine and fatigue. Experiments with rodents, which allow direct manipulation
      of brain serotonin and dopamine during exercise, clearly indicate that increased
      serotoninergic activity reduces performance, while increased dopaminergic
      activity is associated with increased performance. Nevertheless, experiments with
      humans, particularly those involving nutritional supplementation or
      pharmacological manipulations, have yielded conflicting results on the
      relationship between serotonin, dopamine and fatigue. The only clear and
      reproducible effect observed in humans is increased performance in hot
      environments after treatment with inhibitors of dopamine reuptake. Because the
      serotonergic and dopaminergic systems interact with each other, the serotonin-to
      dopamine ratio seems to be more relevant for determining fatigue than analyzing
      or manipulating only one of the two transmitters. Finally, physical training
      protocols induce neuroplasticity, thus modulating the action of these
      neurotransmitters in order to improve physical performance.

PMID- 29069230
TI  - Effects of N-acetylcysteine on spinal cord oxidative stress biomarkers in rats
      with neuropathic pain.
AB  - N-acetylcysteine (NAC) inhibits nociceptive transmission. This effect has been
      associated partly with its antioxidant properties. However, the effect of NAC on
      the levels of lipid hydroperoxides (a pro-oxidant marker), content of ascorbic
      acid (a key antioxidant molecule of nervous tissue) and total antioxidant
      capacity (TAC) is unknown. Thus, our study assessed these parameters in the
      lumbosacral spinal cord of rats with chronic constriction injury (CCI) of the
      sciatic nerve, one of the most commonly employed animal models of neuropathic
      pain. Thirty-six male Wistar rats weighing 200-300 g were equally divided into
      the following groups: Naive (rats did not undergo surgical manipulation); Sham
      (rats in which all surgical procedures involved in CCI were used except the
      ligature), and CCI (rats in which four ligatures were tied loosely around the
      right common sciatic nerve). All rats received intraperitoneal injections of NAC
      (150 mg.kg-1.day-1) or saline for 1, 3, or 7 days. Rats were killed 1, 3, and 7
      days after surgery. NAC treatment prevented the CCI-induced increase in lipid
      hydroperoxide levels only at day 1, although the amount was higher than that
      found in naive rats. NAC treatment also prevented the CCI-induced increase in
      ascorbic acid content, which occurred at days 1, 3, and 7. No significant change
      was found in TAC with NAC treatment. The changes observed here may be related to
      the antinociceptive effect of NAC because modulation of oxidative-stress
      parameters seemed to help normalize the spinal cord oxidative status altered by
      pain.

PMID- 29069232
TI  - Qualitative and quantitative analysis of oropharyngeal swallowing in Down
      syndrome.
AB  - PURPOSE: To describe the qualitative and quantitative temporal analysis of
      oropharyngeal swallowing in children diagnosed with Down syndrome (DS) through a
      case series study of six individuals aged 4 to 17 months (mean age = 11.16
      months; median = 12 months). METHODS: Qualitative and quantitative temporal
      analysis of swallowing using videofluoroscopy and specific software. The
      following parameters were assessed: presence or absence of oral incoordination,
      labial sphincter sealing incompetence, oral residue, posterior oral spillage,
      laryngotracheal penetration and aspiration, pharyngeal and total oral transit
      time (TOTT). RESULTS: Qualitative analysis identified individuals with disorders
      in at least four of the swallowing parameters investigated. Only one individual
      presented total oral transit time (TOTT) different from the others. No difference
      was observed between the cases regarding pharyngeal transit time. CONCLUSION:
      Qualitative swallowing disorders are observed in children with DS, with
      difference in TOTT only in the case report of the youngest infant.

PMID- 29069234
TI  - Predicting the successfulness of parathyroidectomy: new lessons from an old
      challenge.

PMID- 29069233
TI  - Intra-atrial catheter: a viable option for insertion beyond the central veins.

PMID- 29069231
TI  - Myostatin promotes distinct responses on protein metabolism of skeletal and
      cardiac muscle fibers of rodents.
AB  - Myostatin is a novel negative regulator of skeletal muscle mass. Myostatin
      expression is also found in heart in a much less extent, but it can be
      upregulated in pathological conditions, such as heart failure. Myostatin may be
      involved in inhibiting protein synthesis and/or increasing protein degradation in
      skeletal and cardiac muscles. Herein, we used cell cultures and isolated muscles
      from rats to determine protein degradation and synthesis. Muscles incubated with
      myostatin exhibited an increase in proteolysis with an increase of Atrogin-1,
      MuRF1 and LC3 genes. Extensor digitorum longus muscles and C2C12 myotubes
      exhibited a reduction in protein turnover. Cardiomyocytes showed an increase in
      proteolysis by activating autophagy and the ubiquitin proteasome system, and a
      decrease in protein synthesis by decreasing P70S6K. The effect of myostatin on
      protein metabolism is related to fiber type composition, which may be associated
      to the extent of atrophy mediated effect of myostatin on muscle.

PMID- 29069235
TI  - Blood pressure variability: another puzzle piece.

PMID- 29069237
TI  - Comparing costs of renal replacement therapy in a Brazilian city: a case for
      improvement of our health policies.

PMID- 29069236
TI  - The cost of renal replacement therapy in Brazil and the story of the short
      blanket.

PMID- 29069239
TI  - Factors associated with mortality in a population with acute kidney injury
      undergoing hemodialysis in Peru.
AB  - INTRODUCTION: Patients with acute kidney injury (AKI) in developing countries are
      described in a profile of young age, with less comorbidities, with unifactorial,
      and with a lower mortality compared to patients in developed countries.
      OBJECTIVE: To assess mortality in patients with acute kidney injury undergoing
      hemodialysis (HD) and its associated factors in a developing country setting.
      METHODS: Retrospective study. Demographic, clinical, and mortality variables were
      collected from patients who presented AKI and underwent HD between January 2014
      and December 2015 at a national reference hospital in Lima, Peru. Risk ratios
      (RR) and 95% confidence intervals (95%CI) were estimated through Poisson
      regressions. RESULTS: Data from 72 patients with AKI that underwent HD were
      analyzed, 66.7% of them were < 64 years old, and 40.2% of all patients died
      undergoing HD. Crude analysis showed higher mortality among those who used
      vasopressors, but lower mortality among those with creatinine values > 8.9 mg/dL.
      The adjusted analysis showed that having had a creatinine level of > 8.9 mg/dL,
      compared to a creatinine level of < 5.2 mg/dL at the time of initiating HD, was
      associated with 74% less probability of death. CONCLUSION: Four out of every ten
      AKI patients undergoing HD die. Higher levels of creatinine were associated with
      lower probability of mortality.

PMID- 29069240
TI  - Prevalence of chronic kidney disease in a city of southeast Brazil.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is a worldwide public health alarming
      problem. OBJECTIVE: This study investigated the estimated prevalence of kidney
      disease in diabetic and high-risk hypertensive patients to cardiovascular disease
      registered in Hiperdia program of a city of southeast of Brazil. METHODS: It is a
      transversal study conducted between May 2014 and August 2015. The study has
      included randomly 243 diabetic and high-risk hypertensive patients to
      cardiovascular disease which were originally referred from primary health care to
      the Hiperdia. CKD was classified based on cause, Glomerular Filtration Rate
      (GFR), and albumin creatinine ratio (ACR). Were considered abnormalities GFR < 60
      mL/min/1.73m2 and/or ACR >= 30 mg/g. RESULTS: Of the 243 patients, 89 (36.6%)
      showed alterations in renal function markers in the first collection. Of these,
      60 patients had a GFR < 60 mL/min/1.73 m2 and 25 the GFR was < 45 mL/min/1.73 m2.
      The ACR was >= 30 mg/g in 43 patients and eight of the values were > 1000 mg/g.
      In 15 patients studied were found both changes. Of the 89 participants with
      abnormal renal function markers in the first collection 63 held the second test
      and 42 kept the changes being diagnosed with CKD. None of these patients had
      prior knowledge of the diagnosis of kidney disease and the need for consultation
      with the nephrologist. CONCLUSION: The prevalence of CKD was 17.3% of disease in
      the population studied.

PMID- 29069241
TI  - Perceptions of hemodialysis patients about dietary and fluid restrictions.
AB  - INTRODUCTION: Dietary regimen for hemodialysis (HD) patients is complicate and
      identifying characteristics and reasons of those most likely to experience
      difficulty in adhering to dietary restrictions is important. OBJECTIVE: To
      quantify HD patient's perceptions about dietary and fluid restrictions,
      acknowledge individual reasons that facilitate or complicate their adherence, and
      also their relationship with demographic, nutritional and clinical
      characteristics. METHODS: Multi-center cross-sectional study in five dialysis
      facilities. HD patients (n = 147; 48% male; age: 51,3 +/- 13,6 years) were
      encouraged to score on a scale of 0 to 10 their perception of the degree of
      difficulty to adhere the nutritional advice regarding control of sodium, fluid,
      potassium and phosphorus intake. RESULTS: Sodium score was 4(1-7), fluids 6(3-8),
      potassium 4(2-6) and phosphate 6(3-8). Percentage of patients who perceived a
      greater difficulty (score >= 6) to control fluids and phosphate intake was higher
      than for sodium and potassium. Participants with excessive % interdialytic weight
      gain (%IDWG) had a higher score for fluids; the ones with hypercalemia perceived
      more difficulty to control potassium intake than others as well as
      hyperphosphatemic patients compared to normophosphatemic to control phosphorus
      intake. Participants with a greater difficulty to control sodium intake also
      perceived a greater difficulty to control fluids, potassium and phosphate intake.
      CONCLUSION: Participants perceived a greater difficulty to control fluid and
      phosphate intake rather than sodium and potassium, higher perceptions scores were
      associated with subgroups and with worse control of clinical parameters.
      Moreover, patients with a greater difficulty to control some dietary item also
      found harder to control the other ones.

PMID- 29069238
TI  - Urinary cytokine profiles according to the site of blockade of the renin
      angiotensin system in nephrectomized rats.
AB  - INTRODUCTION: It is still unknown how the pharmacological inhibition of the Renin
      Angiotensin System (RAS) impacts the levels of inflammation and fibrosis
      biomarkers. OBJECTIVE: This study sought to evaluate the effect of enalapril,
      candesartan and aliskiren on urinary levels of cytokines in a model of chronic
      kidney disease (CKD). METHODS: Male Wistar rats were submitted to surgical
      removal of 3/4 of renal parenchyma to induce CKD (3/4 nephrectomy), or subjected
      to sham surgery (control). Animals were then randomized into five groups: Sham
      surgery receiving vehicle; 3/4 Nephrectomy receiving vehicle; 3/4 Nephrectomy
      receiving enalapril (10 mg/kg); 3/4 Nephrectomy receiving candesartan (10 mg/kg)
      and 3/4 Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake,
      mean arterial pressure (MAP) and urinary concentrations of creatinine, urea,
      albuminuria, Na+, K+, interleukin (IL) -1beta, IL-6, IL-10 and transforming
      growth factor beta (TGF-beta) were measured. RESULTS: Nephrectomy significantly
      impaired renal function, increased MAP and altered the levels of all evaluated
      cytokines in urine. Enalapril, candesartan and aliskiren improved renal function
      and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group.
      Candesartan and aliskiren decreased IL-1beta, while only candesartan reduced TGF
      beta and only aliskiren increased IL-10. CONCLUSION: Enalapril, candesartan and
      aliskiren presented similar effects on improving renal function and reducing MAP
      and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile
      differed according to the treatment, suggesting that differential mechanisms were
      triggered in response to the site of RAS blockade.

PMID- 29069242
TI  - Cut-off value for absolute lymphocytes as an alternative for the immunophenotypic
      analysis of CD3+ T cells in the monitoring of immunosuppressive therapy with
      thymoglobulin.
AB  - INTRODUCTION: Immunosuppression of T lymphocytes is required for preventing acute
      rejection after transplantation and for the treatment of chronic autoimmune and
      inflammatory diseases. The laboratory monitoring for this therapy is the
      measurement of T cells by immunophenotyping, aiming the target value of less than
      20 cells per uL. OBJECTIVE: To establish a cut-off point for the total number of
      lymphocytes in the automated blood cell count that reflects less than twenty T
      cells uL by immunophenotyping. METHODS: We studied and evaluated 242 kidney
      transplant patients that had results of automated blood cell count and
      quantification of T cells by immunophenotyping technique. The patients were
      divided into two groups, depending on the T lymphocyte immunophenotyping rates
      established by lower and higher than 20 cells per uL. After, we evaluated the cut
      off point for lymphocytes in the blood cell count with a specificity of 100% to
      exclude patients with high levels of T lymphocytes. RESULTS: We found that the
      cut-off point of 70 lymphocytes per uL obtained by automated blood cell count
      showed 100% of specificity to exclude patients with T-cell counts higher than 20
      cells per uL by immunophenotyping. CONCLUSION: The results found in this study
      may be helpful to monitor the immunosuppressive therapy in kidney transplant
      patients in places where a flow cytometer is not available, or when this
      equipment is not present in the full routine.

PMID- 29069243
TI  - Ventricular arrhythmia in chronic kidney disease patients.
AB  - Patients with chronic kidney disease (CKD) are susceptible to the occurrence of
      ventricular arrhythmias. The leading cause of death in dialysis patients is
      cardiac arrhythmias. The pathophysiology of arrhythmias in this population is
      complex and seems to be related to structural cardiac abnormalities caused by
      CKD, associated with several triggers, such as water and electrolyte disorders,
      hormonal conditions, arrhythmogenic drugs, and the dialysis procedure itself.
      Little is known about the clinical outcomes in CKD patients with asymptomatic
      ventricular arrhythmias. The results of treatments with anti-arrhythmic drugs and
      invasive devices are controversial in these patients, according to the available
      literature. The aim of this study was to review this often-neglected topic, which
      is of special importance in the CKD population.

PMID- 29069244
TI  - Educational practices in diabetic patient and perspective of health professional:
      a systematic review.
AB  - This systematic review has sought to identify the multidisciplinary scientific
      production, addressing factors for proper diabetes mellitus management focusing
      on health education, from the perspective of the patient and the professional.
      The goal was to synthesize the knowledge produced and point out its implications
      for the practice of patient care. A search was conducted in PubMed, Medline,
      SCOPUS, LILACS and BIREME. The intervention programs present methodologies and
      different structures, although the theoretical basis is education for self
      management. The evaluation methodologies for effectiveness of educational
      programs focused on the number of subscriptions and stay in groups. Some studies
      also evaluated psychological, social and pathophysiological parameters. The
      results show qualitative improvements in self-care, humanization in care, and
      quality of life of patients. The evidence shows that there seems to be a positive
      response to the intervention programs whenever comparing the physiological,
      psychological, educational and social parameters, initial and final of the
      studies.

PMID- 29069245
TI  - Belatacept in kidney transplantation - past and future perspectives.
AB  - Calcineurin inhibitors (CNIs) are used widely for maintenance immunosuppression
      in renal transplant recipients. However, their side effect profile has led
      researchers to attempt to find safer alternatives that can maintain effective
      long-term immunosuppression with less toxicity. Belatacept is a CTLA4-Ig molecule
      designed to block the costimulatory B7-CD28 signal needed for activation of
      effector T cells. While it has shown great promise in clinical trials, it has
      made halting progress towards replacing CNIs in actual clinical practice. The
      BENEFIT trial revealed some of the advantages of belatacept in terms of
      maintaining renal function after transplant and reducing some of the metabolic
      side effects of CNIs related to hypertension and dyslipidemia. Despite that, some
      cautionary signals have emerged as well, in that belatacept-treated patients
      experience higher acute rejection rates and greater risk for PTLD. Furthermore,
      the requirement for monthly intravenous infusions has presented logistical and
      cost challenges for widespread adoption.

PMID- 29069246
TI  - Hypercalcemia in children: three cases report with unusual clinical
      presentations.
AB  - Hypercalcemia is a rare condition in childhood; the most common causes are
      primary hyperparathyroidism, malignancy, prolonged immobilisation,
      thyrotoxicosis, thiazide diuretic, supplements containing calcium, milk-alkali
      syndrome, vitamin D intoxication, infections and idiopathic. We present three
      cases of severe hypercalcemia of unusual causes in children. The first patient
      had high fever, poor general condition, weight loss and myalgia. Extensive
      preliminary investigation did not define the etiology, but a review of medical
      history revealed prolonged contact with pet bird and a positive serology for
      Chlamydia confirmed the diagnosis of psittacosis. The second patient had
      generalized lymphadenopathy and hepatosplenomegaly with fever a month ago.
      Paracoccidioides brasiliensis was identified in myelogram; the patient showed
      partial improvement with the use of co-trimoxazole, with subsequent emergence of
      multiple osteolytic lesions. A smear of gastric lavage was positive for
      Mycobacterium tuberculosis and the patient was treated with rifampicin,
      isoniazid, ethambutol and pyrazinamide, with improvement of clinical condition.
      The third patient was treated by hypercalciuria and idiopathic hypomagnesiuria
      with daily use of cholecalciferol; the patient had a two quilograms of weight
      loss in the past two months. No cause of hypercalcemia could be detected in
      laboratory workout. The capsules of cholecalciferol were analyzed and presented
      an amount of 832,000 IU of vitamin D per capsule. Acute hypercalcemia in
      childhood may be due to exogenous vitamin D intoxication, as well as infectious
      causes. The possible causal relationship between psittacosis and occurrence of
      hypercalcemia alert to the need for detailed investigation of the epidemiological
      antecedents.

PMID- 29069247
TI  - Reversal of uremic tumoral calcinosis by optimization of clinical treatment of
      bone and mineral metabolism disorder.
AB  - Tumoral calcinosis is an uncommon type of extraosseous calcification
      characterized by large rubbery or cystic masses containing calcium-phosphate
      deposits. The condition prevails in the periarticular tissue with preservation of
      osteoarticular structures. Elevated calcium-phosphorus products and severe
      secondary hyperparathyroidism are present in most patients with uremic tumoral
      calcionosis (UTC). Case report of an obese secondary to chronic
      glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD)
      reported the appearance of painless tumors in the medial surface of fifth finger
      and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor
      adherence to CAPD. The patient was transferred to the "tidal" modality of
      peritoneal dialysis and after was treated by hemodialysis, despite the
      persistence of severe hyperparathyroidism progressive reduction of UTC until near
      to its complete disappearance. Nowadays, one year after patient received deceased
      donor kidney transplantation, he presents with an improvement in secondary
      hyperparathyroidism. UTC should be included in the elucidation of periarticular
      calcification of every patient on dialysis. Relevant laboratory findings such as
      secondary hyperparathyroidism and elevated calcium- phosphorus products in the
      presence of periarticular calcification should draw attention to the diagnosis of
      UTC.

PMID- 29069248
TI  - Point of care kidney ultrasonography and its role in the diagnosis of urinary
      obstruction: a case report.
AB  - INTRODUCTION: Ultrasonography (US) is a rapid, non-invasive and safe procedure
      that allows the nephrologist to obtain vital information to the bedside, as well
      as allows to guide the procedures for nephrology practice. CASE REPORT: Male
      patient, elderly with hypertension, diabetes mellitus and chronic kidney disease
      presents with infraumbilical protrusion that the Point of Care US (POCUS),
      performed by the nephrologist, proved to be a large bladder with a diverticulum.
      In addition, the US enabled the nephrologist to diagnose bilateral
      hydronephrosis, preservation of the cortico-medullary differentiation and
      echotexture of the right kidney, post-voiding urinary retention, urinary catheter
      placement and functional and morphological monitoring of the urinary tract after
      surgical correction of the infravesical obstruction. CONCLUSION: POCUS assessment
      of the renal tract may become the new standard of care among nephrologists by
      enabling the expansion of clinical information in a timely fashion, allowing
      faster resolution of cases and permitting the monitoring of the treatment done.

PMID- 29069249
TI  - Genitourinary tuberculosis - a rare presentation of a still frequent infection in
      renal transplant recipients.
AB  - Mycobacterium tuberculosis infection in renal transplant recipients is associated
      with significant morbidity and mortality. Genitourinary tuberculosis is a less
      frequent presentation and a high level of suspicion is needed to avoid treatment
      delay. Management is challenging due to the interaction of calcineurin inhibitors
      with antituberculous medications and the known side effects of these drugs, with
      higher prevalence in this population. The authors present a case of a renal
      transplant recipient with urinary and constitutional symptoms whom is diagnosed
      with tuberculosis after a prostatic biopsy in an already disseminated stage and
      develops hepatotoxicity to antituberculous therapy.

PMID- 29069250
TI  - Dysfunctional eating behaviors, anxiety, and depression in Italian boys and
      girls: the role of mass media.
AB  - OBJECTIVE: Extensive research has implicated identification with characters in
      mass media in the emergence of disordered eating behavior in adolescents. We
      explored the possible influence of the models offered by television (TV) on
      adolescents' body image, body uneasiness, eating-disordered behavior, depression,
      and anxiety. METHODS: Three hundred and one adolescents (aged 14-19) from
      southern Italy participated. They completed a questionnaire on media exposure and
      body dissatisfaction, the Eating Disorder Inventory-2, the Body Uneasiness Test,
      the Beck Depression Inventory, and the State-Trait Anxiety Inventory - Form Y.
      RESULTS: The main factors contributing to females' eating-disordered behaviors
      were their own desires to be similar to TV characters, the amount of reality and
      entertainment TV they watched, and the discrepancy between their perceptions of
      their bodies and those of TV characters. Friends' desire to be similar to TV
      characters contributed most to depression, anxiety, body uneasiness, and eating
      disorders for both males and females. CONCLUSION: Our data confirm that extensive
      watching of reality and entertainment TV correlates with eating-disordered
      behavior among females. Moreover, the well-known negative effects of the media on
      adolescents' eating-disordered behaviors may also be indirectly transmitted by
      friends who share identification with TV characters.

PMID- 29069251
TI  - Reappraising the dimensional structure of the PTSD Checklist: lessons from the
      DSM-IV-based PCL-C.
AB  - OBJECTIVE: The dimensional structure of posttraumatic stress disorder (PTSD) has
      been extensively debated, but the literature is still inconclusive and contains
      gaps that require attention. This article sheds light on hitherto unvisited
      methodological issues, reappraising several key models advanced for the DSM-IV
      based civilian version of the PTSD Checklist (PCL-C) as to their configural and
      metric structures. METHODS: The sample comprised 456 women, interviewed at 6-8
      weeks postpartum, who attended a high-complexity facility in Rio de Janeiro,
      Brazil. Confirmatory factor analysis (CFA) and exploratory structural equation
      models (ESEM) were used to evaluate the dimensional structure of the PCL-C.
      RESULTS: The original three-factor solution was rejected, along with the four
      factor structures most widely endorsed in the literature (PTSD-dysphoria and PTSD
      numbing models). Further exploration supported a model comprised of two factors
      (re-experience/avoidance and numbing/hyperarousal). CONCLUSION: These findings
      are at odds with the dimensional structure proposed in both DSM-IV and DSM-5.
      This also entails a different presumption regarding the latent structure of PTSD
      and how the PCL should be operationalized.

PMID- 29069252
TI  - Stress, trauma, and posttraumatic stress disorder in migrants: a comprehensive
      review.
AB  - OBJECTIVE: There is growing evidence supporting the association between migration
      and posttraumatic stress disorder (PTSD). Considering the growing population of
      migrants and the particularities of providing culturally sensitive mental health
      care for these persons, clinicians should be kept up to date with the latest
      information regarding this topic. The objective of this study was to critically
      review the literature regarding migration, trauma and PTSD, and mental health
      services. METHODS: The PubMed, SciELO, LILACS, and ISI Web of Science databases
      were searched for articles published in Portuguese, English, Spanish, or French,
      and indexed from inception to 2017. The following keywords were used: migration,
      mental health, mental health services, stress, posttraumatic stress disorder, and
      trauma. RESULTS: Migration is associated with specific stressors, mainly related
      to the migratory experience and to the necessary process of acculturation
      occurring in adaptation to the host country. These major stressors have potential
      consequences in many areas, including mental health. The prevalence of PTSD among
      migrants is very high (47%), especially among refugees, who experience it at
      nearly twice the rate of migrant workers. CONCLUSIONS: Mental health
      professionals must be trained to recognize and provide appropriate care for
      posttraumatic and/or stress-related disorders among migrants.

PMID- 29069253
TI  - Plasma IL-17A levels in patients with late-life depression.
AB  - OBJECTIVE: A consistent body of research has confirmed that patients with major
      depressive disorder (MDD) have increased concentrations of pro-inflammatory
      cytokines, including IL-6, TNF-alpha, IL-1beta, the soluble IL-2 receptor, and C
      reactive protein, compared to controls; however, there is limited information on
      IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e.,
      patients with late-life depression (LLD), is conspicuously missing from the
      literature. The purpose of this study was to investigate the role of IL-17A in
      LLD. METHODS: A convenience sample of 129 individuals, 74 with LLD and 55 non
      depressed controls, were enrolled in this study. The Mann-Whitney U test was used
      to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's
      rank order correlation was used to investigate correlation of these levels with
      clinical, neuropsychological, and cognitive assessments. RESULTS: Plasma IL-17A
      levels were not statistically different between LLD patients and controls (p =
      0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate
      significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant
      correlation was observed with cognitive assessments (rho = 0.22, p = 0.01).
      CONCLUSION: Our findings do not support an association between plasma IL-17A
      levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment
      in LLD patients. If this finding is confirmed in future longitudinal studies,
      modulation of the T-helper 17 cell (Th17) immune response may be a treatment
      target for cognitive impairment in this population.

PMID- 29069254
TI  - Accuracy of transient elastography-FibroScan(r), acoustic radiation force impulse
      (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index
      compared with liver biopsy in patients with chronic hepatitis C.
AB  - OBJECTIVES: Although liver biopsy is the gold standard for determining the degree
      of liver fibrosis, issues regarding its invasiveness and the small amount of
      liver tissue evaluated can limit its applicability and interpretation in clinical
      practice. Non-invasive evaluation methods for liver fibrosis can address some of
      these limitations. The aim of this study was to evaluate the accuracy of
      transient elastography-FibroScan(r), acoustic radiation force impulse (ARFI),
      enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio
      index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C.
      METHODS: We evaluated chronic hepatitis C patients who were followed at the
      Division of Clinical Gastroenterology and Hepatology, Hospital das Clinicas,
      Department of Gastroenterology of University of Sao Paulo School of Medicine, Sao
      Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was
      determined by a receiver operating characteristic (ROC) curve analysis, and
      fibrosis was classified as significant fibrosis (>=F2), advanced fibrosis (>=F3),
      or cirrhosis (F4). The Obuchowski method was also used to determine the
      diagnostic accuracy of each method at the various stages of fibrosis. In total,
      107 FibroScan(r), 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were
      performed. RESULTS: A total of 107 patients were included in the study. The areas
      under the ROC curve (AUROCs) according to fibrosis degree were as follows:
      significant fibrosis (>=F2): FibroScan(r): 0.83, FIB-4: 0.76, ELF: 0.70, APRI:
      0.69, and ARFI: 0.67; advanced fibrosis (>=F3): FibroScan(r): 0.85, ELF: 0.82,
      FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1,
      FibroScan(r): 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient
      elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were
      F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62,
      0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67,
      respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION:
      Transient elastography remained the most effective method for evaluating all
      degrees of fibrosis. The accuracy of all methodologies was best at F4.

PMID- 29069255
TI  - Cytogenomic assessment of the diagnosis of 93 patients with developmental delay
      and multiple congenital abnormalities: The Brazilian experience.
AB  - OBJECTIVE: The human genome contains several types of variations, such as copy
      number variations, that can generate specific clinical abnormalities. Different
      techniques are used to detect these changes, and obtaining an unequivocal
      diagnosis is important to understand the physiopathology of the diseases. The
      objective of this study was to assess the diagnostic capacity of multiplex
      ligation-dependent probe amplification and array techniques for etiologic
      diagnosis of syndromic patients. METHODS: We analyzed 93 patients with
      developmental delay and multiple congenital abnormalities using multiplex
      ligation-dependent probe amplifications and arrays. RESULTS: Multiplex ligation
      dependent probe amplification using different kits revealed several changes in
      approximately 33.3% of patients. The use of arrays with different platforms
      showed an approximately 53.75% detection rate for at least one pathogenic change
      and a 46.25% detection rate for patients with benign changes. A concomitant
      assessment of the two techniques showed an approximately 97.8% rate of
      concordance, although the results were not the same in all cases. In contrast
      with the array results, the MLPA technique detected ~70.6% of pathogenic changes.
      CONCLUSION: The obtained results corroborated data reported in the literature,
      but the overall detection rate was higher than the rates previously reported, due
      in part to the criteria used to select patients. Although arrays are the most
      efficient tool for diagnosis, they are not always suitable as a first-line
      diagnostic approach because of their high cost for large-scale use in developing
      countries. Thus, clinical and laboratory interactions with skilled technicians
      are required to target patients for the most effective and beneficial molecular
      diagnosis.

PMID- 29069256
TI  - Experimental study of histological changes in vascular loops according to the
      duration of the postoperative period: Application in reconstructive microsurgery.
AB  - OBJECTIVES: To analyze the histological changes observed in venous grafts
      subjected to arterial blood flow as a function of the duration of the
      postoperative period to optimize their use in free flap reconstructions. METHOD:
      Twenty-five rats (7 females and 18 males) underwent surgery. Surgeries were
      performed on one animal per week. Five weeks after the first surgery, the same
      five animals were subjected to an additional surgery to assess the presence or
      absence of blood flow through the vascular loop, and samples were collected for
      histological analysis. This cycle was performed five times. RESULTS: Of the rats
      euthanized four to five weeks after the first surgery, no blood flow was observed
      through the graft in 80% of the cases. In the group euthanized three weeks after
      the first surgery, no blood flow was observed in 20% of the cases. In the groups
      euthanized one to two weeks after the first surgery, blood flow through the
      vascular loop was observed in all animals. Moreover, intimal proliferation tended
      to increase with the duration of the postoperative period. Two weeks after
      surgery, intimal proliferation increased slightly, whereas strong intimal
      proliferation was observed in all rats evaluated five weeks after surgery.
      CONCLUSION: Intimal proliferation was the most significant change noted in venous
      grafts as a function of the duration of the postoperative period and was directly
      correlated with graft occlusion. In cases in which vascular loops are required
      during free flap reconstruction, both procedures should preferably be performed
      during the same surgery.

PMID- 29069257
TI  - Long-term efficiency of cataract surgery with hydrophilic acrylic Ioflex
      intraocular lens.
AB  - OBJECTIVE: To evaluate the efficiency of long-term cataract surgery using low
      cost intraocular lens implantation in community campaigns. METHODS: Fifty-eight
      randomly selected patients were evaluated four years after phacoemulsification
      and Ioflex intraocular lens implantation. Causes of low visual acuity related to
      the intraocular lens were evaluated, and treatment costs were calculated.
      RESULTS: The mean age of patients was 72+/-10.2 years. Four years after surgery,
      25 eyes (43.0%) had decreased visual acuity related to the intraocular lens:
      posterior capsule opacification was noted in 24 eyes (41.3%), and intraocular
      lens opacification was noted in one eye (1.7%). The total cost of the post
      surgical complication treatments represented 6.3% of the initial budget of the
      entire surgical patient group. CONCLUSIONS: The efficiency of cataract surgery
      with low-cost Ioflex intraocular lens implantation was significantly reduced in a
      long-term follow-up study because postoperative complications related to
      intraocular lenses emerged at higher rates than when the gold-standard treatment
      was used.

PMID- 29069258
TI  - Early menarche and teenager pregnancy as risk factors for morbid obesity among
      reproductive-age women: A case-control study.
AB  - OBJECTIVES: The aim of this study was to evaluate potential risk factors,
      including non-communicable diseases, for morbid obesity in women between 20 and
      49 years of age. METHODS: We performed a case-control study with 110 morbidly
      obese women and 110 women with adequate weight who were matched by age and with a
      1:1 case to control ratio. All women were between 20 to 49 years old and non
      menopausal. Possible risk factors were evaluated through a self-report
      questionnaire assessing socio-demographic, obstetric and gynecological
      characteristics, presence of non-communicable diseases and habits. Multiple
      logistic regression was used to estimate the odds ratio with respective
      confidence intervals. RESULTS: Menarche under 12 years old, teenage pregnancy and
      lower educational level were shown to be risk factors for morbid obesity among
      women of reproductive age. Incidences of non-communicable diseases (diabetes,
      hypertension, dyslipidemia, liver disease, lung disease, thyroid dysfunction, and
      joint pain) were increased in women with morbid obesity. CONCLUSIONS: Early
      menarche, teenage pregnancy and low education level are risk factors for the
      occurrence of morbid obesity in women of reproductive age. Some non-communicable
      diseases were already more prevalent in women with morbid obesity even before 50
      years of age.

PMID- 29069259
TI  - Endoscopic endonasal approach for mass resection of the pterygopalatine fossa.
AB  - OBJECTIVES: Access to the pterygopalatine fossa is very difficult due to its
      complex anatomy. Therefore, an open approach is traditionally used, but morbidity
      is unavoidable. To overcome this problem, an endoscopic endonasal approach was
      developed as a minimally invasive procedure. The surgical aim of the present
      study was to evaluate the utility of the endoscopic endonasal approach for the
      management of both benign and malignant tumors of the pterygopalatine fossa.
      METHOD: We report our experience with the endoscopic endonasal approach for the
      management of both benign and malignant tumors and summarize recent
      recommendations. A total of 13 patients underwent surgery via the endoscopic
      endonasal approach for pterygopalatine fossa masses from 2014 to 2016. This case
      group consisted of 12 benign tumors (10 juvenile nasopharyngeal angiofibromas and
      two schwannomas) and one malignant tumor. RESULTS: No recurrent tumor developed
      during the follow-up period. One residual tumor (juvenile nasopharyngeal
      angiofibroma) that remained in the cavernous sinus was stable. There were no
      significant complications. Typical sequelae included hypesthesia of the maxillary
      nerve, trismus, and dry eye syndrome. CONCLUSION: The low frequency of
      complications together with the high efficacy of resection support the use of the
      endoscopic endonasal approach as a feasible, safe, and beneficial technique for
      the management of masses in the pterygopalatine fossa.

PMID- 29069260
TI  - The value of high-flow nasal cannula oxygen therapy after extubation in patients
      with acute respiratory failure.
AB  - OBJECTIVE: To investigate the value of high-flow nasal cannula oxygen therapy
      after extubation in patients with acute respiratory failure. METHODS: A single
      center, prospective, randomized, controlled pilot trial was conducted between
      January 2013 and December 2014. Sixty enrolled patients were randomized
      immediately after extubation into either a high-flow nasal cannula group (n=30)
      or an air entrainment mask group (n=30) at a fixed inspired oxygen fraction
      (40%). The success rate of oxygen therapy, respiratory and hemodynamic parameters
      and subjective discomfort (using a visual analogue scale) were assessed at 24h
      after extubation. RESULTS: The two groups were comparable at extubation. A total
      of 46 patients were successfully treated including 27 patients in the high-flow
      nasal cannula group and 19 patients in the air entrainment mask group. Compared
      to the air entrainment mask group, the success rate of oxygen therapy and the
      partial pressure of arterial oxygen were significantly higher and the respiratory
      rate was lower in the high-flow nasal cannula group. In addition, less discomfort
      related to interface displacement and airway dryness was observed in the high
      flow nasal cannula group than in the air entrainment mask group. CONCLUSIONS: At
      a fixed inspired oxygen fraction, the application of a high-flow nasal cannula
      after extubation achieves a higher success rate of oxygen therapy and less
      discomfort at 24h than an air entrainment mask in patients with acute respiratory
      failure.

PMID- 29069261
TI  - Caring for critically ill patients outside intensive care units due to full
      units: a cohort study.
AB  - OBJECTIVES: This study sought to analyze the clinical and epidemiologic
      characteristics of critically ill patients who were denied intensive care unit
      admission due to the unavailability of beds and to estimate the direct costs of
      treatment. METHODS: A prospective cohort study was performed with critically ill
      patients treated in a university hospital. All consecutive patients denied
      intensive care unit beds due to a full unit from February 2012 to February 2013
      were included. The data collected included clinical data, calculation of costs,
      prognostic scores, and outcomes. The patients were followed for data collection
      until intensive care unit admission or cancellation of the request for the
      intensive care unit bed. Vital status at hospital discharge was noted, and
      patients were classified as survivors or non-survivors considering this endpoint.
      RESULTS: Four hundred and fifty-four patients were analyzed. Patients were
      predominantly male (54.6%), and the median age was 62 (interquartile range (ITQ):
      47 - 73) years. The median APACHE II score was 22.5 (ITQ: 16 - 29). Invasive
      mechanical ventilation was used in 298 patients (65.6%), and vasoactive drugs
      were used in 44.9% of patients. The median time of follow-up was 3 days (ITQ: 2 -
      6); after this time, 204 patients were admitted to the intensive care unit and
      250 had the intensive care unit bed request canceled. The median total cost per
      patient was US$ 5,945.98. CONCLUSIONS: Patients presented a high severity in
      terms of disease scores, had multiple organ dysfunction and needed multiple
      invasive therapeutic interventions. The study patients received intensive care
      with specialized consultation during their stay in the hospital wards and
      presented high costs of treatment.

PMID- 29069262
TI  - An activating mutation in the CRHR1 gene is rarely associated with pituitary
      dependent hyperadrenocorticism in poodles.
AB  - OBJECTIVES: Pituitary-dependent hyperadrenocorticism is the most common cause of
      naturally occurring hypercortisolism in dogs. CRHR1 expression in human and dog
      corticotrophinomas suggested that this gene affects pituitary tumorigenesis. The
      present study aimed to investigate mutations in the CRHR1 coding region in
      poodles with pituitary-dependent hyperadrenocorticism. METHODS: Fifty poodles
      with pituitary-dependent hyperadrenocorticism and 50 healthy poodles were
      studied. Genomic DNA was amplified by PCR and analyzed by Sanger sequencing.
      RESULTS: The novel CRHR1 p.V97M mutation was identified in one dog. This valine
      residue, located in the amino-terminal extracellular domain, exhibits high
      affinity for its corticotropin-releasing hormone (CRH) ligand. Bioinformatic
      analysis revealed structural rearrangements in the mutant protein, with a 17%
      increase in the surface binding affinity between CRHR1 and CRH. In vitro
      functional studies showed that mutant CRHR1 induced higher ACTH secretion than
      the wild type after stimulation with human CRH. CONCLUSION: These results suggest
      that germline activating mutations in CRHR1 may be a rare cause of pituitary
      hyperadrenocorticism in poodles.

PMID- 29069263
TI  - A Biomechanical Analysis of the Interlock Suture and a Modified Kessler-Loop Lock
      Flexor Tendon Suture.
AB  - OBJECTIVE: In this work, we attempted to develop a modified single-knot Kessler
      loop lock suture technique and compare the biomechanical properties associated
      with this single-knot suture technique with those associated with the
      conventional modified Kessler and interlock suture techniques. METHODS: In this
      experiment, a total of 18 porcine flexor digitorum profundus tendons were
      harvested and randomly divided into three groups. The tendons were transected and
      then repaired using three different techniques, including modified Kessler suture
      with peritendinous suture, interlock suture with peritendinous suture, and
      modified Kessler-loop lock suture with peritendinous suture. Times required for
      suturing were recorded and compared among groups. The groups were also compared
      with respect to 2-mm gap load, ultimate failure load, and gap at failure.
      RESULTS: For tendon repair, compared with the conventional modified Kessler
      suture technique, the interlock and modified Kessler-loop lock suture techniques
      resulted in significantly improved biomechanical properties. However, there were
      no significant differences between the interlock and modified Kessler-loop lock
      techniques with respect to biomechanical properties, gap at failure, and time
      required. CONCLUSIONS: The interlock and modified Kessler-loop lock techniques
      for flexor tendon sutures produce similar mechanical characteristics in vitro.

PMID- 29069264
TI  - Nurse perception of care of hospitalized older adults - a comparative study
      between northern and central regions of Portugal.
AB  - OBJECTIVE: to analyze the relationship between the perceptions of nurses about
      geriatric care (GC) environment and geriatric nurses' knowledge and attitudes
      according to unit type considering the northern and central regions of Portugal.
      METHOD: a cross-sectional study was developed among 1068 Portuguese's nurses in
      five hospitals. The instrument was Geriatric Institutional Assessment Profile -
      Portuguese version. The independent samples t-test was when the assumption of
      normality was verified, otherwise, the Mann-Whitney U test was used. The level of
      significance was 5%. RESULTS: the profile of perceptions of GC showed a
      relatively homogeneous pattern (no statistically significant results were found).
      For the geriatric care environment scale, only the CC/ED units presented
      significant differences in all considered subscales (resource availability; aging
      sensitive care; institutional values; and continuity of care), with more positive
      perceptions among nurses in the northern region. In Professional Issues scales,
      only the scale perception of burden related with upsetting behaviors revealed
      significant differences between regions in all specialties. CONCLUSION: the
      findings suggest the need for increased investment by hospital leaders to promote
      a geriatric nursing practice environment that supports the specialized needs of
      hospitalized older adults.

PMID- 29069266
TI  - The PAHO/WHO Regional Network of Interprofessional Health Education.

PMID- 29069265
TI  - Knowledge in palliative care of nursing professionals at a Spanish hospital.
AB  - OBJECTIVE: to determine the level of knowledge in palliative care of nursing
      staff at a Spanish tertiary care hospital. METHOD: descriptive, cross-sectional
      study. Data were collected about the results of the Spanish version of the
      Palliative Care Quiz for Nurses (PCQN), sociodemographic aspects, education level
      and experience in the field of palliative care. Univariate and bivariate
      descriptive analysis was applied. Statistical significance was set at p < 0.05 in
      all cases. RESULTS: 159 professionals participated (mean age 39.51 years +/-
      10.25, with 13.96 years +/- 10.79 of professional experience) 54.7% possessed
      experience in palliative care and 64.2% educational background (mainly basic
      education). The mean percentage of hits on the quiz was 54%, with statistically
      significant differences in function of the participants' education and experience
      in palliative care. CONCLUSIONS: although the participants show sufficient
      knowledge on palliative care, they would benefit from a specific training
      program, in function of the mistaken concepts identified through the quiz, which
      showed to be a useful tool to diagnose professionals' educational needs in
      palliative care.

PMID- 29069267
TI  - Prevalence of household falls in long-lived adults and association with extrinsic
      factors.
AB  - OBJECTIVE: to identify the prevalence of falls among older adults and the
      extrinsic factors associated with them. METHOD: population-based cross-sectional
      study with 350 older adults. A household survey was conducted using a
      questionnaire addressing socio-demographic, clinical, and environmental
      characteristics. Data were analyzed using Stata Software V.10. Pearson's chi
      square test and logistic regression analysis were used with stepwise criteria for
      selection of variables in the model, with measures of effect expressed in
      Prevalence Ratio. For input into the multiple model, the variables with p <= 0.20
      were considered. All ethical care regarding research on human beings has been
      observed and respected. RESULTS: the prevalence of falls was 46.9%. The extrinsic
      factors associated with falls were: stairs, uneven floor and pets in the main
      entrance, lack of anti-slip loose throw rugs and slippery floor in the kitchen,
      lack of anti-slip loose throw rugs and objects on the floor in the room, lack of
      grab bars in the shower, lack of grab bars in the toilet and switch away from the
      bathroom door (p <0.05). CONCLUSION: falls are frequent in long-lived adults. The
      identification of the extrinsic factors associated with the occurrence of this
      event can help in its prevention.

PMID- 29069269
TI  - Comparing Interrater reliability between eye examination and eye self-examination
      1.
AB  - OBJECTIVE: to compare Interrater reliability concerning two eye assessment
      methods. METHOD: quasi-experimental study conducted with 324 college students
      including eye self-examination and eye assessment performed by the researchers in
      a public university. Kappa coefficient was used to verify agreement. RESULTS:
      reliability coefficients between Interraters ranged from 0.85 to 0.95, with
      statistical significance at 0.05. The exams to check for near acuity and
      peripheral vision presented a reasonable kappa >0.2. The remaining coefficients
      were higher, ranging from very to totally reliable. CONCLUSION: comparatively,
      the results of both methods were similar. The virtual manual on eye self
      examination can be used to screen for eye conditions.

PMID- 29069268
TI  - Validation to Spanish of the Caring Assessment Tool (CAT-V).
AB  - OBJECTIVE: to translate and validate to Spanish the Caring Assessment Scale tool,
      CAT-V, by Joanne Duffy, within the framework of Jean Watson; as a secondary
      objective, it is proposed to evaluate its psychometric properties. There are
      tools designed to measure the patient's perception of provided cares, including
      CAT-V, the subject of our interest, in a way that it can be used in Spanish
      speaking patients. METHODS: to meet the objectives, it was performed sequential
      translation and retro-translation of the scale to be validated, through a
      standardized procedure. The final version of that scale was validated in a sample
      of 349 patients from four public and two private hospitals in Madrid, Spain.
      RESULTS: The instrument was translated and validated with high internal
      consistency (Cronbach's alpha .953). The subsequent factor analysis revealed a
      three-factor structure, not coincident with the data from the US population.
      CONCLUSION: it is considered that the translation of CAT-V is a suitable
      instrument to be used in the evaluation of patient care in Ibero-american health
      centers whose language is Spanish.

PMID- 29069270
TI  - Cardiovascular health in Brazilian state capitals 1.
AB  - OBJECTIVE: to estimate the prevalence of ideal cardiovascular health indicators
      in the Brazilian population, according to gender, age, education and region of
      residence. METHOD: cross-sectional study that used data from 41,134 participants
      of the Surveillance System of Risk and Protective Factors for Chronic Diseases by
      Telephone Survey (Vigitel). The ideal cardiovascular health assessment considers
      four behavioral factors: not smoking; body mass index less than 25 kg/m2;
      practicing physical activity, eating fruits and vegetables five or more times per
      day; and two clinical factors (no diagnosis of diabetes or hypertension). The sum
      of factors at ideal levels results in a score ranging from zero (worse
      cardiovascular health) to six (ideal cardiovascular health). RESULTS: considering
      the six factors, only 3.4% of the studied population presented ideal levels of
      cardiovascular health, with the majority of participants (57.6%) presenting three
      or four ideal factors. Women had higher prevalence of ideal cardiovascular health
      (3.8% versus 2.9% for men) (p < 0.0001). CONCLUSION: the findings of this study
      are consistent with the elevated risk of mortality from cardiovascular disease,
      observed in the Brazilian population. This may contribute to a better
      understanding of the scenario of cardiovascular health in the urban population of
      the country.

PMID- 29069271
TI  - Intensive treatment of speech disorders in robin sequence: a case report.
AB  - PURPOSE: To describe the speech of a patient with Pierre Robin Sequence (PRS) and
      severe speech disorders before and after participating in an Intensive Speech
      Therapy Program (ISTP). METHODS: The ISTP consisted of two daily sessions of
      therapy over a 36-week period, resulting in a total of 360 therapy sessions. The
      sessions included the phases of establishment, generalization, and maintenance. A
      combination of strategies, such as modified contrast therapy and speech sound
      perception training, were used to elicit adequate place of articulation. The ISTP
      addressed correction of place of production of oral consonants and maximization
      of movement of the pharyngeal walls with a speech bulb reduction program. Therapy
      targets were addressed at the phonetic level with a gradual increase in the
      complexity of the productions hierarchically (e.g., syllables, words, phrases,
      conversation) while simultaneously addressing the velopharyngeal hypodynamism
      with speech bulb reductions. RESULTS: Re-evaluation after the ISTP revealed
      normal speech resonance and articulation with the speech bulb. Nasoendoscopic
      assessment indicated consistent velopharyngeal closure for all oral sounds with
      the speech bulb in place. CONCLUSION: Intensive speech therapy, combined with the
      use of the speech bulb, yielded positive outcomes in the rehabilitation of a
      clinical case with severe speech disorders associated with velopharyngeal
      dysfunction in Pierre Robin Sequence.

PMID- 29069272
TI  - Effects of a language program in the social functioning of children at elementary
      school.
AB  - PURPOSE: the purpose of this study was to describe a language stimulation
      program, including teacher training and practical activities in the classroom,
      and investigate the effectiveness of this action on the social functioning and
      behavioral problems of elementary school children. METHODS: 136 children from six
      classrooms of a public school and their teachers participated in this research.
      Of these, half were given the language stimulation program: 16 hours of training
      for teachers and 9 meetings in the classroom with activities for students. The
      activities involved instruction for the use of language reflection and practice
      with the narrative structure. Teachers filled out questionnaires about the social
      skills and behavior problems of their students before and after the program.
      RESULTS: there was no statistically significant difference between the research
      groups pre- and post- program in terms of assertiveness/ social resourcefulness
      (1st and 5th grades) and cooperation/affection (1st and 3rd grades). In the
      research groups, children of the 3rd grade, different from the 1st and the 5th
      grade, showed more evolution in their self-control abilities, which may be
      related to the lower frequency of externalizing problems in this group.
      CONCLUSION: the language program had positive effects on social
      assertiveness/resourcefulness skills and social cooperation/affection.

PMID- 29069273
TI  - Portal of the elderly: development and evaluation of the website with information
      about the aging process and the main speech, language and hearing disorders that
      affect the elderly.
AB  - PURPOSE: This research aimed to develop and evaluate a website with information
      on Speech-language therapy area with focus on the aging process. A website
      containing information with simple language, clear purpose and concise content
      was designed based on scientific evidence. METHODS: The Flesch Index was used to
      check the material readability, with 50% of the content corresponding to "easy"
      and 50% of the content corresponding to "difficult". The website development
      followed the steps: analysis and planning, modeling, implementation and
      evaluation. Evaluators invited to participate were part of the following
      categories: elderly people, caregivers and speech-language therapists. The sample
      consisted of 10 elderly, 8 caregivers and 10 speech-language therapists. Most
      individuals (89.28%) were females, who often accessed the Internet (78.57%) and
      had different educational levels. RESULTS: Statistical analyses were performed
      using the Kruskal-Wallis test and Spearman correlation coefficient. The website's
      content was classified as "adequate" and the website's technical quality as
      "excellent". There was no statistically significant difference between the
      categories and subscales or the overall score. CONCLUSION: The website can be
      considered an accessible material, and a source of consultation and
      complementation of information about the theme, as well as an important tool for
      effecting the information transmission process.

PMID- 29069274
TI  - Undifferentiated Pancreatic Carcinomas Display Enrichment for Frequency and
      Extent of PD-L1 Expression by Tumor Cells.
AB  - Objectives: Programmed death ligand 1 (PD-L1) expression in pancreatic ductal
      adenocarcinoma (PDA) has been described, but unselected PDAs have shown limited
      clinical responsiveness to anti-programmed death 1 (PD-1)/PD-L1 therapy. Methods:
      We studied 24 cases of undifferentiated pancreatic carcinoma (UPC) using
      immunohistochemistry for PD-L1 (E1L3N clone), CD3, CD20, CD68, and DNA mismatch
      repair proteins in this study. Slides were scored for extent of PD-L1 expression
      on tumor cells and tumor-infiltrating immune cells. Results: PD-L1 expression was
      more frequent in UPCs than in PDAs (63% vs 15%, P < .01). The extent of PD-L1
      expression was greater in UPCs, with 13 (87%) of 15 cases containing 10% or more
      positive tumor cells compared with three of seven PDAs (P = .05). Both tumor
      groups showed similar numbers of tumor-infiltrating T cells, B cells, and
      macrophages. Conclusions: UPC is enriched for PD-L1 expression in frequency and
      extent, relative to conventional PDA. Anti-PD-1/PD-L1 agents may represent a
      valuable therapeutic approach for this subset of highly aggressive pancreatic
      carcinoma.

PMID- 29069275
TI  - Submucosal Invasive Depth Predicts Lymph Node Metastasis and Poor Prognosis in
      Submucosal Invasive Esophageal Squamous Cell Carcinoma.
AB  - Objectives: Lymph node metastasis (LNM) in submucosal invasive esophageal
      squamous cell carcinoma (SM-ESCC) is a prognostic factor. The aim of this study
      was to identify a histopathologic predictor of LNM in SM-ESCC. Methods: In total,
      108 patients who underwent an esophagectomy and lymph node dissection without
      preoperative therapy and who were pathologically diagnosed with SM-ESCC were
      enrolled in this study. Relationships between several clinicopathologic factors
      and LNM were examined. Results: A multivariate analysis revealed that a tumor
      size of 35 mm or more (P = .0025), submucosal invasive depth (SID) of 2,000 MUm
      or more (P = .013), and lymphatic infiltration (P < .0001) were significant
      independent predictors of LNM. In addition, there were significant differences in
      recurrence-free survival curves between patients with SID less than 2,000 MUm or
      not (P = .029) and tumor size less than 35 mm or not (P = .049). Conclusions:
      This study suggests that SID may predict not only LNM but also poor prognosis.

PMID- 29069276
TI  - The Genomic Grade Index predicts postoperative clinical outcome in patients with
      soft-tissue sarcoma.
AB  - Background: Soft-tissue sarcomas (STSs) are a group of rare, heterogeneous, and
      aggressive tumors, with high metastatic risk and relatively few efficient
      systemic therapies. We hypothesized that the Genomic Grade Index (GGI), a 108
      gene signature previously developed in early-stage breast cancer, might improve
      the prognostic assessment of patients with early-stage STS. Patients and methods:
      We collected gene expression and clinicopathological data of 678 operated STS,
      and searched for correlations between the GGI-based classification and
      clinicopathological variables, including the metastasis-free survival (MFS).
      Results: Based on GGI, 275 samples (41%) were classified as 'GGI-low' and 403
      (59%) as 'GGI-high'. The 'GGI-high' class was more associated with poor-prognosis
      features than the 'GGI-low' class: pathological grade 3 (P = 9.50E-11),
      undifferentiated sarcomas and leiomyosarcomas (P < 1.00E-06), location in
      extremities (P < 1.00E-06), and complex genetic profile (P = 2.1E-20). The 5-year
      MFS was 53% (95%CI 47-59) in the 'GGI-high' class versus 78% (95%CI 72-85) in the
      'GGI-low' class (P = 3.02E-11), with a corresponding hazard ratio for metastatic
      relapse equal to 2.92 (95%CI 2.10-4.07; P = 2.23E-10). In multivariate analysis,
      the GGI-based classification remained significant, whereas the pathological grade
      did not. In fact, the GGI-based classification stratified the patients with
      pathological grades 1 and 2 and those with pathological grade 3 in two classes
      with different 5-year MFS. Comparison of the GGI and CINSARC multigene signatures
      revealed similar correlations with clinicopathological variables, which were,
      however, stronger with GGI than with CINSARC, a strong concordance (71%) in terms
      of low-risk or high-risk classifications, and independent prognostic value for
      MFS in multivariate analysis, suggesting complementary prognostic information.
      Conclusion: GGI refines the prediction of MFS in operated STS and might improve
      the tailoring of adjuvant chemotherapy. Further clinical validation is warranted
      in larger retrospective, then prospective series, as well as the functional
      validation of relevant genes that could provide new therapeutic targets.

PMID- 29069277
TI  - A novel pretherapeutic gene expression-based risk score for treatment guidance in
      gastric cancer.
AB  - Background: Perioperative chemotherapy is an established treatment of advanced
      gastric cancer patients. Treatment selection is based on clinical staging (cT).
      We aimed to establish and validate a prognostic score including clinical and
      molecular factors, to optimize treatment decisions for these patients. Patients
      and methods: We analyzed 626 carcinomas of the stomach and of the gastro
      esophageal junction from two academic centers including primarily resected and
      pre-/perioperatively treated patients. Patients were divided into a training (N =
      269) and validation (N = 357) set. Expression of 11 target genes was measured by
      quantitative PCR in resected tumors. A risk score to predict overall survival
      (OS) was generated and validated. Intra-tumoral heterogeneity was assessed by
      analyzing 50 tumor areas from 10 patients. Results: A risk score including the
      expression of CCL5, CTNNB1, EXOSC3 and LZTR1 and the clinical parameters cT,
      tumor localization and histopathologic type suggested two groups with a
      significant difference in OS [hazard ratio (HR) 0.30; 95% confidence interval
      (CI) 0.17-0.52]. The risk score was successfully validated in an independent
      cohort (HR 0.32; 95% CI 0.21-0.51; P < 0.001) as well as in subgroups of
      primarily resected (HR 0.30; 95% CI 0.17-0.54; P < 0.001) and pre
      /perioperatively treated patients (HR 0.37; 95% CI 0.17-0.81; P = 0.009). A
      significant difference in OS of high- and low-risk patients was also found in
      primarily resected patients with intestinal (HR 0.45; 95% CI 0.23-0.90; P =
      0.020) and nonintestinal-type carcinomas (HR 0.1; 95% CI 0.02-0.42; P < 0.001).
      Intra-tumor heterogeneity analysis indicated a classification reliability of 95%
      for a supposed analysis of three biopsies. Conclusion: The identified risk score
      could substantially contribute to an improved management of gastric cancer
      patients in the context of perioperative chemotherapy.

PMID- 29069278
TI  - Performance Validity, Neurocognitive Disorder, and Post-concussion Symptom
      Reporting in Service Members with a History of Mild Traumatic Brain Injury.
AB  - Objective: To examine the influence of different performance validity test (PVT)
      cutoffs on neuropsychological performance, post-concussion symptoms, and rates of
      neurocognitive disorder and postconcussional syndrome following mild traumatic
      brain injury (MTBI) in active duty service members. Method: Participants were 164
      service members (Age: M = 28.1 years [SD = 7.3]) evaluated on average 4.1 months
      (SD = 5.0) following injury. Participants were divided into three mutually
      exclusive groups using original and alternative cutoff scores on the Test of
      Memory Malingering (TOMM) and the Effort Index (EI) from the Repeatable Battery
      for the Assessment of Neuropsychological Status (RBANS): (a) PVT-Pass, n = 85;
      (b) Alternative PVT-Fail, n = 53; and (c) Original PVT-Fail, n = 26. Participants
      also completed the Neurobehavioral Symptom Inventory. Results: The PVT-Pass group
      performed better on cognitive testing and reported fewer symptoms than the two
      PVT-Fail groups. The Original PVT-Fail group performed more poorly on cognitive
      testing and reported more symptoms than the Alternative PVT-Fail group. Both PVT
      Fail groups were more likely to meet DSM-5 Category A criteria for mild and major
      neurocognitive disorder and symptom reporting criteria for postconcussional
      syndrome than the PVT-Pass group. When alternative PVT cutoffs were used instead
      of original PVT cutoffs, the number of participants with valid data meeting
      cognitive testing criteria for neurocognitive disorder or postconcussional
      syndrome decreased dramatically. Conclusion: PVT performance is significantly and
      meaningfully related to overall neuropsychological outcome. By using only
      original cutoffs, clinicians and researchers may miss people with invalid
      performances.

PMID- 29069279
TI  - Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG
      island methylator phenotype (CIMP)-high colorectal cancer.
AB  - Background: Hypermethylation of promoter CpG islands [CpG island methylator
      phenotype (CIMP)] represents a unique pathway for the development of colorectal
      cancer (CRC), characterized by lack of chromosomal instability and a low rate of
      adenomatous polyposis coli (APC) mutations, which have both been correlated with
      taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor,
      also has a low rate of APC mutations. This phase II study evaluated taxane
      sensitivity in SBA and CIMP-high CRC. Patients and methods: The primary objective
      was Response Evaluation Criteria in Solid Tumors version 1.1 response rate.
      Eligibility included Eastern Cooperative Oncology Group performance status 0/1,
      refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was
      initially administered at a dose of 260 mg/m2 every 3 weeks but was reduced to
      220 mg/m2 owing to toxicity. Results: A total of 21 patients with CIMP-high CRC
      and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy
      assessable population (patients who received at least three doses of the
      treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade
      3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%),
      dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP
      high CRC cohort and two partial responses were seen in the SBA cohort. Median
      progression-free survival was significantly greater in the SBA cohort than in the
      CIMP-high CRC cohort (3.2 months compared with 2.1 months, P = 0.03). Neither APC
      mutation status nor CHFR methylation status correlated with efficacy in the CIMP
      high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived
      xenograft validated the activity of taxanes in this disease type. Conclusion:
      Although preclinical studies suggested taxane sensitivity was associated with
      chromosomal stability and wild-type APC, we found that nab-paclitaxel was
      inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel
      therapeutic option for SBA.

PMID- 29069280
TI  - PROSPERous: high-throughput prediction of substrate cleavage sites for 90
      proteases with improved accuracy.
AB  - Summary: Proteases are enzymes that specifically cleave the peptide backbone of
      their target proteins. As an important type of irreversible post-translational
      modification, protein cleavage underlies many key physiological processes. When
      dysregulated, proteases' actions are associated with numerous diseases. Many
      proteases are highly specific, cleaving only those target substrates that present
      certain particular amino acid sequence patterns. Therefore, tools that
      successfully identify potential target substrates for proteases may also identify
      previously unknown, physiologically relevant cleavage sites, thus providing
      insights into biological processes and guiding hypothesis-driven experiments
      aimed at verifying protease-substrate interaction. In this work, we present
      PROSPERous, a tool for rapid in silico prediction of protease-specific cleavage
      sites in substrate sequences. Our tool is based on logistic regression models and
      uses different scoring functions and their pairwise combinations to subsequently
      predict potential cleavage sites. PROSPERous represents a state-of-the-art tool
      that enables fast, accurate and high-throughput prediction of substrate cleavage
      sites for 90 proteases. Availability and implementation:
      http://prosperous.erc.monash.edu/. Contact: jiangning.song@monash.edu or
      geoff.webb@monash.edu or r.pike@latrobe.edu.au. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29069282
TI  - Chromatin accessibility prediction via a hybrid deep convolutional neural
      network.
AB  - Motivation: A majority of known genetic variants associated with human-inherited
      diseases lie in non-coding regions that lack adequate interpretation, making it
      indispensable to systematically discover functional sites at the whole genome
      level and precisely decipher their implications in a comprehensive manner.
      Although computational approaches have been complementing high-throughput
      biological experiments towards the annotation of the human genome, it still
      remains a big challenge to accurately annotate regulatory elements in the context
      of a specific cell type via automatic learning of the DNA sequence code from
      large-scale sequencing data. Indeed, the development of an accurate and
      interpretable model to learn the DNA sequence signature and further enable the
      identification of causative genetic variants has become essential in both genomic
      and genetic studies. Results: We proposed Deopen, a hybrid framework mainly based
      on a deep convolutional neural network, to automatically learn the regulatory
      code of DNA sequences and predict chromatin accessibility. In a series of
      comparison with existing methods, we show the superior performance of our model
      in not only the classification of accessible regions against background sequences
      sampled at random, but also the regression of DNase-seq signals. Besides, we
      further visualize the convolutional kernels and show the match of identified
      sequence signatures and known motifs. We finally demonstrate the sensitivity of
      our model in finding causative noncoding variants in the analysis of a breast
      cancer dataset. We expect to see wide applications of Deopen with either public
      or in-house chromatin accessibility data in the annotation of the human genome
      and the identification of non-coding variants associated with diseases.
      Availability and implementation: Deopen is freely available at
      https://github.com/kimmo1019/Deopen. Contact: ruijiang@tsinghua.edu.cn.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29069281
TI  - Melatonin and its relationship to plant hormones.
AB  - Background: Plant melatonin appears to be a multi-regulatory molecule, similar to
      those observed in animals, with many specific functions in plant physiology. In
      recent years, the number of studies on melatonin in plants has increased
      significantly. One of the most studied actions of melatonin in plants is its
      effect on biotic and abiotic stress, such as that produced by drought, extreme
      temperatures, salinity, chemical pollution and UV radiation, among others. Scope:
      This review looks at studies in which some aspects of the relationship between
      melatonin and the plant hormones auxin, cytokinin, gibberellins, abscisic acid,
      ethylene, jasmonic acid and salicylic acid are presented. The effects that some
      melatonin treatments have on endogenous plant hormone levels, their related genes
      (biosynthesis, catabolism, receptors and transcription factors) and the
      physiological actions induced by melatonin, mainly in stress conditions, are
      discussed. Conclusions: Melatonin is an important modulator of gene expression
      related to plant hormones, e.g. in auxin carrier proteins, as well as in
      metabolism of indole-3-acetic acid (IAA), gibberellins, cytokinins, abscisic acid
      and ethylene. Most of the studies performed have dealt with the auxin-like
      activity of melatonin which, in a similar way to IAA, is able to induce growth in
      shoots and roots and stimulate root generation, giving rise to new lateral and
      adventitious roots. Melatonin is also able to delay senescence, protecting
      photosynthetic systems and related sub-cellular structures and processes. Also,
      its role in fruit ripening and post-harvest processes as a gene regulator of
      ethylene-related factors is relevant. Another decisive aspect is its role in the
      pathogen-plant interaction. Melatonin appears to act as a key molecule in the
      plant immune response, together with other well-known molecules such as nitric
      oxide and hormones, such as jasmonic acid and salicylic acid. In this sense, the
      discovery of elevated levels of melatonin in endophytic organisms associated with
      plants has thrown light on a possible novel form of communication between
      beneficial endophytes and host plants via melatonin.

PMID- 29069283
TI  - Bayesian data integration for quantifying the contribution of diverse
      measurements to parameter estimates.
AB  - Motivation: Computational models in biology are frequently underdetermined, due
      to limits in our capacity to measure biological systems. In particular,
      mechanistic models often contain parameters whose values are not constrained by a
      single type of measurement. It may be possible to achieve better model
      determination by combining the information contained in different types of
      measurements. Bayesian statistics provides a convenient framework for this,
      allowing a quantification of the reduction in uncertainty with each additional
      measurement type. We wished to explore whether such integration is feasible and
      whether it can allow computational models to be more accurately determined.
      Results: We created an ordinary differential equation model of cell cycle
      regulation in budding yeast and integrated data from 13 different studies
      covering different experimental techniques. We found that for some parameters, a
      single type of measurement, relative time course mRNA expression, is sufficient
      to constrain them. Other parameters, however, were only constrained when two
      types of measurements were combined, namely relative time course and absolute
      transcript concentration. Comparing the estimates to measurements from three
      additional, independent studies, we found that the degradation and transcription
      rates indeed matched the model predictions in order of magnitude. The predicted
      translation rate was incorrect however, thus revealing a deficiency in the model.
      Since this parameter was not constrained by any of the measurement types
      separately, it was only possible to falsify the model when integrating multiple
      types of measurements. In conclusion, this study shows that integrating multiple
      measurement types can allow models to be more accurately determined. Availability
      and implementation: The models and files required for running the inference are
      included in the Supplementary information. Contact: l.wessels@nki.nl.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29069284
TI  - Molecular Epidemiology of Tuberculosis in British Columbia, Canada: A 10-Year
      Retrospective Study.
AB  - Background: Understanding regional molecular epidemiology allows for the
      development of more efficient tuberculosis prevention strategies in low-incidence
      settings. Methods: We analyzed 24-locus mycobacterial interspersed repetitive
      unit-variable-number tandem repeat (MIRU-VNTR) genotyping for 2290 Mycobacterium
      tuberculosis clinical isolates collected in the province of British Columbia
      (BC), Canada, in 2005-2014. Laboratory data for each isolate were linked to case
      level clinical and demographic data. These data were used to describe the
      molecular epidemiology of tuberculosis across the province. Results: We detected
      >1500 distinct genotypes across the 4 major M. tuberculosis lineages, reflecting
      BC's diverse population. Disease site and clustering rates varied across
      lineages, and MIRU-VNTR was used to group the 2290 isolates into 189 clusters (2
      70 isolates per cluster), with an overall clustering rate of 42.4% and an
      estimated local transmission rate of 34.1%. Risk factors for clustering varied
      between Canadian-born and foreign-born individuals; the former had increased odds
      (odds ratio, 7.8; 95% confidence interval [CI], 6.2-9.6) of belonging to a
      genotypic cluster, although nearly one-quarter of clusters included both Canadian
      and foreign-born persons. Large clusters (>=10 cases) occurred more frequently
      within the M. tuberculosis Euro-American lineage, and individual-level risk
      factors associated with belonging to a large cluster included being Canadian born
      (adjusted odds ratio, 3.3; 95% CI, 2.3-4.8), residing in a rural area (2.3; 1.2
      4.5), and illicit drug use (2.0; 1.2-3.4). Conclusions: Although tuberculosis in
      BC largely arises through reactivation of latent tuberculosis in foreign-born
      persons, locally transmitted infections occur in discrete populations with
      distinct disease and risk factor profiles, representing groups for targeted
      interventions.

PMID- 29069285
TI  - Transabdominal ultrasound-guided multifetal pregnancy reduction in 10 cases of
      monkeys.
AB  - Intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) in nonhuman
      primates, e.g. rhesus and cynomolgus monkeys, has been widely used in researches
      of reproductive and developmental biology, and the success rate has been improved
      significantly. However, unwanted multiple pregnancy occurs frequently during the
      ICSI-ET in monkeys, most of which leads to miscarriages. To improve the birth
      rate of pregnancies and to safeguard health of host and baby monkeys, multifetal
      pregnancy reduction (MPR) is necessary. In this study, a total of 10 monkeys with
      multiple pregnancies received MPR through transabdominal ultrasound-guided
      potassium chloride injection into beating hearts of selective fetuses. To assess
      MPR efficiency, 31 monkeys with normal singleton pregnancies and 25 monkeys with
      twin pregnancies without MPR were used as controls. The aim of the reduction is
      to keep only one fetus, no matter twin or triplet pregnancy originally. Our
      results show that six cases of MPR were successful and all of them retained
      single fetus. Moreover, about 1 month (30.2 +/- 1.2 days) of gestation is a
      better timing for MPR than later stage (50.7 +/- 1.9 days). We also found that
      the remaining fetuses developed normally with full-term gestation and normal
      birth weight. In conclusion, transabdominal ultrasound-guided potassium chloride
      injection is a safe and effective MPR method for monkeys with multiple
      pregnancies.

PMID- 29069287
TI  - The concomitant apoptosis and EMT underlie the fundamental functions of TGF-beta.
AB  - TGF-beta's multipotent cellular effects and their relations are critical for TGF
      beta's pathophysiological functions. However, these effects may appear to be
      paradoxical in understanding TGF-beta's functions. Apoptosis and epithelial
      mesenchymal transition (EMT) are two fundamental events that are deeply linked to
      various physiological and disease-related processes. These two major cellular
      fates are subtly regulated and can be potently stimulated by TGF-beta, which
      profoundly contribute to the biological roles of TGF-beta. Moreover, these two
      events are also indirectly and directly correlated with TGF-beta-mediated growth
      inhibition and are relevant to the current understanding of the roles of TGF-beta
      in tumorigenesis and cancer progression. Although TGF-beta-induced apoptosis and
      EMT can be singly independent cellular events, they can also be mutually
      exclusive but interrelated concomitant events in various cases. Thus, the
      modulation of apoptosis and EMT is essential for the seemingly paradoxical
      functions of TGF-beta. However, the concomitant effect of TGF-beta on apoptosis
      and EMT, the balance and regulated alterations of them are still been ignored or
      underestimated. This review focuses on the TGF-beta-induced concomitant apoptosis
      and EMT. We aim to provide an insight in understanding their significance,
      balance, and modulation in TGF-beta-mediated biological functions.

PMID- 29069286
TI  - DNA Hydroxymethylation Levels Are Altered in Blood Cells From Down Syndrome
      Persons Enrolled in the MARK-AGE Project.
AB  - Down syndrome (DS) is caused by the presence of part or an entire extra copy of
      chromosome 21, a phenomenon that can cause a wide spectrum of clinically defined
      phenotypes of the disease. Most of the clinical signs of DS are typical of the
      aging process including dysregulation of immune system. Beyond the causative
      genetic defect, DS persons display epigenetic alterations, particularly aberrant
      DNA methylation patterns that can contribute to the heterogeneity of the disease.
      In the present work, we investigated the levels of 5-hydroxymethylcytosine and of
      the Ten-eleven translocation dioxygenase enzymes, which are involved in DNA
      demethylation processes and are often deregulated in pathological conditions as
      well as in aging. Analyses were carried out on peripheral blood mononuclear cells
      of DS volunteers enrolled in the context of the MARK-AGE study, a large-scale
      cross-sectional population study with subjects representing the general
      population in eight European countries. We observed a decrease in 5
      hydroxymethylcytosine, TET1, and other components of the DNA
      methylation/demethylation machinery in DS subjects, indicating that aberrant DNA
      methylation patterns in DS, which may have consequences on the transcriptional
      status of immune cells, may be due to a global disturbance of methylation control
      in DS.

PMID- 29069288
TI  - Lesion development is modulated by the natural estrous cycle and mouse strain in
      a minimally invasive model of endometriosis.
AB  - Many rodent models of endometriosis are invasive, involving surgery to implant
      donor endometrial tissue into recipient animals. Moreover, few studies have
      compared and contrasted lesions between rodent strains and estrous stages without
      exogenous hormone manipulation. This is despite extensive data demonstrating that
      genetic and hormonal factors can influence endometriosis progression. Here, we
      have refined a minimally invasive model of endometriosis using naturally cycling
      mice (donor and recipient matched for cycle phase) to investigate lesion
      development in two different strains (C57BL/6 and BALB/c), induced in estrous
      stages of high and low estrogen (proestrus or estrus, respectively), and with
      varying amounts of donor endometrial tissue (7.5-40 mg), injected
      intraperitoneally. The overall probability of developing endometriosis-like
      lesions was higher in proestrus than estrus, and increased with greater masses of
      donor tissue. Similarly, the total number of lesions (0-3) increased from 7.5 to
      40 mg, and was significantly greater in proestrus C57BL/6 mice but not BALB/cs.
      The dominant lesion type also differed between mouse strains; C57BL/6 mice were
      more likely to develop dense-type lesions, whereas BALB/c mice developed a
      greater proportion of cystic type. These data further support a role for estrogen
      in the development of endometriosis, and that genetic variance can influence the
      degree and characteristics of lesions. Our minimally invasive model would be
      beneficial for studies with outcome measurements particularly sensitive to
      incisional injury, such as pain, or alterations to sex hormones, including
      fertility.

PMID- 29069289
TI  - Distinct dynorphin expression patterns with low- and high-dose estrogen treatment
      in the arcuate nucleus of female rats.
AB  - Kisspeptin (KISS1; encoded by Kiss1) neurons in the arcuate nucleus (ARC)
      coexpress tachykinin 3 (TAC3; also known as neurokinin B) and dynorphin A (PDYN).
      Accordingly, they are termed KNDy neurons and considered to be crucial in
      generating pulsatile release of gonadotropin-releasing hormone. Accumulating
      evidence suggests that Kiss1 and Tac3 are negatively regulated by estrogen.
      However, it has not been fully determined whether and how estrogen modulates Pdyn
      and PDYN. Here, we examined the expression of Pdyn mRNA and PDYN by in situ
      hybridization and immunohistochemistry, respectively, in the ARC of female rats
      after ovariectomy (OVX) and OVX plus low- or high-dose beta-estradiol (E2)
      replacement. We also investigated the effect of E2 on expression of Kiss1, KISS1,
      Tac3, and TAC3. Furthermore, colocalization of PDYN and estrogen receptor alpha
      (ESR1) was determined. Subsequently, we found that low-dose E2 treatment had no
      effect on Pdyn mRNA-expressing cells, but increased PDYN-immunoreactive (ir) cell
      numbers. In contrast, high-dose E2 treatment resulted in prominent reductions in
      both Pdyn mRNA-expressing and PDYN-ir cell numbers. Changes induced by low or
      high doses of E2 were similarly observed in the expression of Kiss1, KISS1, Tac3,
      and TAC3. The majority of PDYN-ir neurons coexpressed ESR1 in all groups. Our
      results indicate that E2 regulates the expression of PDYN, as well as KISS1 and
      TAC3, with regulation by E2 differing according to its levels.

PMID- 29069291
TI  - Cognitive Effects of Multi-Domain Interventions Among Pre-Frail and Frail
      Community-Living Older Persons: Randomized Controlled Trial.
AB  - Background: Cognitive, physical, and nutritional interventions may produce
      different cognitive effects for different groups of older persons. We
      investigated simultaneously the cognitive outcomes of cognitive, physical, and
      nutritional interventions singly and in combinations in older persons with the
      physical frailty phenotype at particular risk of cognitive decline. Method: Pre
      frail and frail participants were randomly allocated to 24 weeks nutritional
      supplementation (N = 49), physical training (N = 48), cognitive training (N =
      50), combination intervention (N = 49), or usual care control (N = 50). Cognitive
      domain and global functions were assessed at baseline (0M), 6 month (6M), and 12
      month (12M). Results: The control group showed declines in z-scores (from -0.100
      to -0.244) of all domains. The cognitive training compared to control group
      showed the greatest increase in global cognition at 6M (0.094 vs -0.174, p =
      .006) and 12M (0.099 vs -0.142, p = .002), immediate memory at 6M (0.164 vs 
      0.211, p = .010) and 12M (0.182 vs -0.142, p = .040), delayed memory at 6M (p =
      .010), and attention at 6M (p = .025). Nutritional intervention showed benefits
      at 6M for immediate memory (p = .028) and delayed memory (p = .024), but physical
      training showed no positive effects. The combination group showed the greatest
      increase for visuospatial construction at 6M (0.215 vs -0.141, p = .010) and 12M
      (0.166 vs -0.180, p = .016), and for global cognition at 12M (p = .016) and
      language at 12M (p = .023). Conclusion: Among frail older persons, cognitive
      training conferred the greatest cognitive benefits. Nutritional and physical
      interventions singly were associated with modest short-term or no cognitive
      benefits, but their combined effects on visuospatial construction should be
      further investigated.

PMID- 29069290
TI  - Potent suppression of both spontaneous and carcinogen-induced colitis-associated
      colorectal cancer in mice by dietary celastrol supplementation.
AB  - Celastrol is an anti-inflammatory natural triterpenoid, isolated from the herb
      Tripterygium wilfordii or thunder god vine. Here, we define mechanisms mediating
      anti-inflammatory activity of celastrol and demonstrate efficacy of a dietary
      celastrol supplement for chemoprevention of inflammation-driven carcinogenesis in
      mice. Dietary celastrol (31.25 ppm in rodent diet from 8 weeks to 25 weeks of
      age) is well tolerated and protects against LPS-induced acute inflammation in
      C57BL/6 mice, potently suppressing LPS-induction of inducible nitric oxide
      synthase (iNOS), cyclooxygenase (COX)-2, Interleukin (IL)-6 and IL-1beta. To test
      whether dietary celastrol suppresses inflammation-driven colorectal cancer (CRC),
      we employed a unique model of spontaneous, inflammation-driven CRC in mice
      harboring a germ line deletion of the p27Kip1 gene and a T cell-specific deletion
      of Smad4 gene (Smad4co/co;Lck-crep27Kip1-/-or DKO), which develop severe
      intestinal inflammation and carcinogenesis as early as 3 months of age. Exposure
      of DKO mice to daily dietary celastrol (12.5 ppm in diet) from 6 weeks of age
      significantly suppressed development of colitis-associated CRC (CAC). Celastrol
      chemoprevention of CAC in this new model of intestinal neoplasia was associated
      with significant suppression of iNOS at 4 months of age, and iNOS, COX-2 and
      NFkappaB at 6 months of age, with significant reduction in inflammatory
      cytokines, IL-6 and IL-1beta. Chemoprevetion of CAC by dietary celastrol was
      further confirmed in the model of azoxymethane (AOM) plus dextran sodium sulfate
      (DSS)-induced carcinogenesis in C57BL/6 mice. These data suggest the potential
      for celastrol as a safe and effective dietary supplement in the chemoprevention
      of CAC in humans.

PMID- 29069292
TI  - Task-Modulated Cortical Representations of Natural Sound Source Categories.
AB  - In everyday sound environments, we recognize sound sources and events by
      attending to relevant aspects of an acoustic input. Evidence about the cortical
      mechanisms involved in extracting relevant category information from natural
      sounds is, however, limited to speech. Here, we used functional MRI to measure
      cortical response patterns while human listeners categorized real-world sounds
      created by objects of different solid materials (glass, metal, wood) manipulated
      by different sound-producing actions (striking, rattling, dropping). In different
      sessions, subjects had to identify either material or action categories in the
      same sound stimuli. The sound-producing action and the material of the sound
      source could be decoded from multivoxel activity patterns in auditory cortex,
      including Heschl's gyrus and planum temporale. Importantly, decoding success
      depended on task relevance and category discriminability. Action categories were
      more accurately decoded in auditory cortex when subjects identified action
      information. Conversely, the material of the same sound sources was decoded with
      higher accuracy in the inferior frontal cortex during material identification.
      Representational similarity analyses indicated that both early and higher-order
      auditory cortex selectively enhanced spectrotemporal features relevant to the
      target category. Together, the results indicate a cortical selection mechanism
      that favors task-relevant information in the processing of nonvocal sound
      categories.

PMID- 29069293
TI  - ARCS: scaffolding genome drafts with linked reads.
AB  - Motivation: Sequencing of human genomes is now routine, and assembly of shotgun
      reads is increasingly feasible. However, assemblies often fail to inform about
      chromosome-scale structure due to a lack of linkage information over long
      stretches of DNA-a shortcoming that is being addressed by new sequencing
      protocols, such as the GemCode and Chromium linked reads from 10 * Genomics.
      Results: Here, we present ARCS, an application that utilizes the barcoding
      information contained in linked reads to further organize draft genomes into
      highly contiguous assemblies. We show how the contiguity of an ABySS H.sapiens
      genome assembly can be increased over six-fold, using moderate coverage (25-fold)
      Chromium data. We expect ARCS to have broad utility in harnessing the barcoding
      information contained in linked read data for connecting high-quality sequences
      in genome assembly drafts. Availability and implementation:
      https://github.com/bcgsc/ARCS/. Contact: rwarren@bcgsc.ca. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29069294
TI  - Isolation and Identification of Rickettsia raoultii in Human Cases: A
      Surveillance Study in 3 Medical Centers in China.
AB  - Background: Rickettsia raoultii is frequently detected in multiple tick species,
      whereas human infection remains scarcely studied. Methods: A surveillance study
      was performed at 3 sentinel hospitals in China, to recruit participants with
      suspected tick exposure. Rickettsia raoultii infection was identified through
      polymerase chain reaction, followed by sequencing, and confirmed serologically.
      Isolation by cell culture was performed and the isolates were genome sequenced.
      Results: Twenty-six subjects were determined to have R. raoultii infection,
      including 7 with asymptomatic infection, 15 with mild to moderate illness, and 4
      with severe illness. Common nonspecific manifestations in the 19 patients with
      mild to moderate or severe illness included fever (100%), malaise (95%), myalgia
      (58%), lymphadenopathy (53%), and nausea (42%). Only 5% of them had rash, and 16%
      had eschar. Scalp eschar and neck lymphadenopathy after a tick bite syndrome was
      only seen in 2 patients. Of the 4 patients with severe complications, 3 developed
      pulmonary edema, and 1 developed clouding of consciousness and lethargy. Frequent
      abnormalities of laboratory testing included leukopenia, thrombocytopenia,
      lymphopenia, neutropenia, hypoproteinemia, and elevated levels of total
      bilirubin, hepatic aminotransferases, lactate dehydrogenase, and creatine kinase.
      All the 19 patients recovered without sequelae after receiving doxycycline
      treatment. Two R. raoultii strains were isolated, and a significantly less
      degraded genome was observed than other more virulent Rickettsia strains,
      indicating a low pathogenicity of the current strain. Conclusions: Human
      infection with R. raoultii has a wide clinical spectrum that ranged from
      subclinical infection to severe complications. Physicians need to be aware of the
      high potential and clinical complexity of R. raoultii infection, to ensure
      appropriate testing and treatment in endemic regions.

PMID- 29069295
TI  - PaRSnIP: sequence-based protein solubility prediction using gradient boosting
      machine.
AB  - Motivation: Protein solubility can be a decisive factor in both research and
      production efficiency, and in silico sequence-based predictors that can
      accurately estimate solubility outcomes are highly sought. Results: In this
      study, we present a novel approach termed PRotein SolubIlity Predictor (PaRSnIP),
      which uses a gradient boosting machine algorithm as well as an approximation of
      sequence and structural features of the protein of interest. Based on an
      independent test set, PaRSnIP outperformed other state-of-the-art sequence-based
      methods by more than 9% in accuracy and 0.17 in Matthew's correlation
      coefficient, with an overall accuracy of 74% and Matthew's correlation
      coefficient of 0.48. Additionally, PaRSnIP provides importance scores for all
      features used in training. We observed higher fractions of exposed residues to
      associate positively with protein solubility and tripeptide stretches with
      multiple histidines to associate negatively with solubility. The improved
      prediction accuracy of PaRSnIP should enable it to predict protein solubility
      with greater reliability and to screen for sequence variants with enhanced
      manufacturability. Availability and implementation: PaRSnIP software is available
      for download under GitHub (https://github.com/RedaRawi/PaRSnIP). Contact: gwo
      yu.chuang@nih.gov. Supplementary information: Supplementary data are available at
      Bioinformatics online.

PMID- 29069296
TI  - xMWAS: a data-driven integration and differential network analysis tool.
AB  - Summary: Integrative omics is a central component of most systems biology
      studies. Computational methods are required for extracting meaningful
      relationships across different omics layers. Various tools have been developed to
      facilitate integration of paired heterogenous omics data; however most existing
      tools allow integration of only two omics datasets. Furthermore, existing data
      integration tools do not incorporate additional steps of identifying sub-networks
      or communities of highly connected entities and evaluating the topology of the
      integrative network under different conditions. Here we present xMWAS, a software
      for data integration, network visualization, clustering, and differential network
      analysis of data from biochemical and phenotypic assays, and two or more omics
      platforms. Availability and implementation: https://kuppal.shinyapps.io/xmwas
      (Online) and https://github.com/kuppal2/xMWAS/ (R). Contact: kuppal2@emory.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29069297
TI  - SeqBox: RNAseq/ChIPseq reproducible analysis on a consumer game computer.
AB  - Summary: Short reads sequencing technology has been used for more than a decade
      now. However, the analysis of RNAseq and ChIPseq data is still computational
      demanding and the simple access to raw data does not guarantee results
      reproducibility between laboratories. To address these two aspects, we developed
      SeqBox, a cheap, efficient and reproducible RNAseq/ChIPseq hardware/software
      solution based on NUC6I7KYK mini-PC (an Intel consumer game computer with a fast
      processor and a high performance SSD disk), and Docker container platform. In
      SeqBox the analysis of RNAseq and ChIPseq data is supported by a friendly GUI.
      This allows access to fast and reproducible analysis also to scientists
      with/without scripting experience. Availability and implementation: Docker
      container images, docker4seq package and the GUI are available at
      http://www.bioinformatica.unito.it/reproducibile.bioinformatics.html. Contact:
      beccuti@di.unito.it. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29069299
TI  - A fast fiducial marker tracking model for fully automatic alignment in electron
      tomography.
AB  - Motivation: Automatic alignment, especially fiducial marker-based alignment, has
      become increasingly important due to the high demand of subtomogram averaging and
      the rapid development of large-field electron microscopy. Among the alignment
      steps, fiducial marker tracking is a crucial one that determines the quality of
      the final alignment. Yet, it is still a challenging problem to track the fiducial
      markers accurately and effectively in a fully automatic manner. Results: In this
      paper, we propose a robust and efficient scheme for fiducial marker tracking.
      Firstly, we theoretically prove the upper bound of the transformation deviation
      of aligning the positions of fiducial markers on two micrographs by affine
      transformation. Secondly, we design an automatic algorithm based on the Gaussian
      mixture model to accelerate the procedure of fiducial marker tracking. Thirdly,
      we propose a divide-and-conquer strategy against lens distortions to ensure the
      reliability of our scheme. To our knowledge, this is the first attempt that
      theoretically relates the projection model with the tracking model. The real
      world experimental results further support our theoretical bound and demonstrate
      the effectiveness of our algorithm. This work facilitates the fully automatic
      tracking for datasets with a massive number of fiducial markers. Availability and
      implementation: The C/C ++ source code that implements the fast fiducial marker
      tracking is available at https://github.com/icthrm/gmm-marker-tracking.
      Markerauto 1.6 version or later (also integrated in the AuTom platform at
      http://ear.ict.ac.cn/) offers a complete implementation for fast alignment, in
      which fast fiducial marker tracking is available by the '-t' option. Contact:
      xin.gao@kaust.edu.sa. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29069300
TI  - ROSC-Pred: web-service for rodent organ-specific carcinogenicity prediction.
AB  - Motivation: Identification of rodent carcinogens is an important task in risk
      assessment of chemicals. SAR methods were proposed to reduce the number of animal
      experiments. Most of these methods ignore information about organ-specificity of
      tumorigenesis. Our study was aimed at the creation of classification models and a
      freely available online service for prediction of rodent carcinogens considering
      the species (rats, mice), sex and tissue-specificity from structural formula of
      compounds. Results: The data from Carcinogenic Potency Database for 1011 organic
      compounds evaluated on the standard two-year rodent carcinogenicity bioassay was
      used for the creation of training sets. Structure-activity relationships models
      for prediction of rodent organ-specific carcinogenicity were created by PASS
      software, which was based on Bayesian-like approach and Multilevel Neighborhoods
      of Atoms descriptors. The average prediction accuracy for training sets
      calculated by leave-one-out and 10-fold cross-validation was 79 and 78.2%,
      respectively. Availability and implementation: Freely available on the web at
      http://www.way2drug.com/ROSC. Contact: alexey.lagunin@ibmc.msk.ru. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29069298
TI  - High Human Immunodeficiency Virus Incidence and Prevalence and Associated Factors
      Among Adolescent Sexual Minority Males-3 Cities, 2015.
AB  - Background: Much has been written about the impact of human immunodeficiency
      virus (HIV) among young (13-24) sexual minority men (SMM). Evidence for concern
      is substantial for emerging adult (18-24 years) SMM. Data documenting the burden
      and associated risk factors of HIV among adolescent SMM (<18 years) remain
      limited. Methods: Adolescent SMM aged 13-18 years were recruited in 3 cities
      (Chicago, New York City, and Philadelphia) for interview and HIV testing. We used
      chi2 tests for percentages of binary variables and 1-way analysis of variance for
      means of continuous variables to assess differences by race/ethnicity in
      behaviors. We calculated estimated annual HIV incidence density (number of HIV
      infections per 100 person-years [PY] at risk). We computed Fisher's exact tests
      to determine differences in HIV prevalence by selected characteristics. Results:
      Of 415 sexually active adolescent SMM with a valid HIV test result, 25 (6%) had a
      positive test. Estimated annual HIV incidence density was 3.4/100 PY; incidence
      density was highest for blacks, followed by Hispanics, then whites (4.1, 3.2, and
      1.1/100 PY, respectively). Factors associated with higher HIV prevalence included
      black race; >=4 male partners, condomless anal sex, and exchange sex in the past
      12 months; and a recent partner who was older, black, HIV-infected, or had ever
      been in jail or prison (P < .05). Conclusions: HIV-related risk behaviors,
      prevalence, and estimated incidence density for adolescent SMM were high,
      especially for minority SMM. Our findings suggest that initiating intervention
      efforts early may be helpful in combating these trends.

PMID- 29069302
TI  - Mechanistic overview of immune checkpoints to support the rational design of
      their combinations in cancer immunotherapy.
AB  - Checkpoint receptor blockers, known to act by blocking the pathways that inhibit
      immune cell activation and stimulate immune responses against tumor cells, have
      been immensely successful in the treatment of cancer. Among several checkpoint
      receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4),
      programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain
      (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3)
      are the most commonly targeted checkpoints for cancer immunotherapy. Six drugs
      including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and
      pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab)
      are approved for the treatment of different types of cancers including both solid
      tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and
      Merkel cell cancer as well as hematological tumors such as classic Hodgkin's
      lymphoma. The main problem with checkpoint blockers is that only a fraction of
      patients respond to the therapy. Insufficient immune activation is considered as
      one of the main reason for low response rates and combination of checkpoint
      blockers has been proposed to increase the response rates. The combination of
      checkpoint blockers was successful in melanoma but had significant adverse
      events. A combination that is selected based on the mechanistic differences
      between checkpoints and the differences in expression of checkpoints and their
      ligands in the tumor microenvironment could have a synergistic effect in a given
      cancer subtype and also have a manageable safety profile. This review aims to
      help in design of optimal checkpoint blocker combinations by discussing the
      mechanistic details and outlining the subtle differences between major
      checkpoints targeted for cancer immunotherapy.

PMID- 29069301
TI  - Investigating transcription factor synergism in humans.
AB  - Proteins are the core and the engine of every process in cells thus the study of
      mechanisms that drive the regulation of protein expression, is essential.
      Transcription factors play a central role in this extremely complex task and they
      synergically co-operate in order to provide a fine tuning of protein expressions.
      In the present study, we designed a mathematically well-founded procedure to
      investigate the mutual positioning of transcription factors binding sites related
      to a given couple of transcription factors in order to evaluate the possible
      association between them. We obtained a list of highly related transcription
      factors couples, whose binding site occurrences significantly group together for
      a given set of gene promoters, identifying the biological contexts in which the
      couples are involved in and the processes they should contribute to regulate.

PMID- 29069303
TI  - A prospective genome-wide study of prostate cancer metastases reveals association
      of wnt pathway activation and increased cell cycle proliferation with primary
      resistance to abiraterone acetate-prednisone.
AB  - Background: Genomic aberrations have been identified in metastatic castration
      resistant prostate cancer (mCRPC), but molecular predictors of resistance to
      abiraterone acetate/prednisone (AA/P) treatment are not known. Patients and
      methods: In a prospective clinical trial, mCRPC patients underwent whole-exome
      sequencing (n = 82) and RNA sequencing (n = 75) of metastatic biopsies before
      initiating AA/P with the objective of identifying genomic alterations associated
      with resistance to AA/P. Primary resistance was determined at 12 weeks of
      treatment using criteria for progression that included serum prostate-specific
      antigen measurement, bone and computerized tomography imaging and symptom
      assessments. Acquired resistance was determined using the end point of time to
      treatment change (TTTC), defined as time from enrollment until change in
      treatment from progressive disease. Associations of genomic and transcriptomic
      alterations with primary resistance were determined using logistic regression,
      Fisher's exact test, single and multivariate analyses. Cox regression models were
      utilized for determining association of genomic and transcriptomic alterations
      with TTTC. Results: At 12 weeks, 32 patients in the cohort had progressed
      (nonresponders). Median study follow-up was 32.1 months by which time 58 patients
      had switched treatments due to progression. Median TTTC was 10.1 months
      (interquartile range: 4.4-24.1). Genes in the Wnt/beta-catenin pathway were more
      frequently mutated and negative regulators of Wnt/beta-catenin signaling were
      more frequently deleted or displayed reduced mRNA expression in nonresponders.
      Additionally, mRNA expression of cell cycle regulatory genes was increased in
      nonresponders. In multivariate models, increased cell cycle proliferation scores
      (>= 50) were associated with shorter TTTC (hazard ratio = 2.11, 95% confidence
      interval: 1.17-3.80; P = 0.01). Conclusions: Wnt/beta-catenin pathway activation
      and increased cell cycle progression scores can serve as molecular markers for
      predicting resistance to AA/P therapy.

PMID- 29069305
TI  - heatmaply: an R package for creating interactive cluster heatmaps for online
      publishing.
AB  - Summary: heatmaply is an R package for easily creating interactive cluster
      heatmaps that can be shared online as a stand-alone HTML file. Interactivity
      includes a tooltip display of values when hovering over cells, as well as the
      ability to zoom in to specific sections of the figure from the data matrix, the
      side dendrograms, or annotated labels. Thanks to the synergistic relationship
      between heatmaply and other R packages, the user is empowered by a refined
      control over the statistical and visual aspects of the heatmap layout.
      Availability and implementation: The heatmaply package is available under the GPL
      2 Open Source license. It comes with a detailed vignette, and is freely available
      from: http://cran.r-project.org/package=heatmaply. Contact:
      tal.galili@math.tau.ac.il. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29069306
TI  - Decaying Wood Preference of Stag Beetles (Coleoptera: Lucanidae) in a Tropical
      Dry-Evergreen Forest.
AB  - Larvae of many insect species, including stag beetles, have a limited mobility
      from their initial oviposition site. The fate of immature stages, therefore,
      depends on the maternal choice of oviposition site. Decaying wood preference by
      stag beetles was studied in a dry-evergreen forest in Chanthaburi province,
      Thailand. From a total of 270 examined logs, 52 contained stag beetles (255
      total), which were identified to eight species from five genera. Aegus chelifer
      chelifer MacLeay, 1819 (Coleoptera: Lucanidae) was the dominant species both by
      occurrence and by number of individuals. The occurrence and numbers of stag
      beetle larvae found in logs was more frequent in those of a moderate decay class,
      which had moderate hardness and water content. Principal component analysis (PCA)
      revealed that logs with stag beetles had relatively high nitrogen content and
      fungal biomass. Thus, selection of oviposition sites by stag beetles was likely
      to depend on both the log decay stage (or hardness) to protect immature stages
      from natural enemies and its nutritional properties to enhance the larval
      performance.

PMID- 29069308
TI  - CLIFinder: identification of LINE-1 chimeric transcripts in RNA-seq data.
AB  - Summary: L1 Chimeric Transcripts (LCTs) are initiated by repeated LINE-1 element
      antisense promoters and include the L1 5'UTR sequence in antisense orientation
      followed by the adjacent genomic region. LCTs have been characterized mainly
      using bioinformatics approaches to query dbEST. To take advantage of NGS data to
      unravel the transcriptome composition, we developed Chimeric LIne Finder
      (CLIFinder), a new bioinformatics tool. Using stranded paired-end RNA-seq data,
      we demonstrated that CLIFinder can identify genome-wide transcribed chimera
      sequences corresponding to potential LCTs. Moreover, CLIFinder can be adapted to
      study transcription from other repeat types. Availability and implementation: The
      code is available at: https://github.com/GReD-Clermont/CLIFinder; and for Galaxy
      users, it is directly accessible in the tool shed at:
      https://toolshed.g2.bx.psu.edu/view/clifinder/clifinder/. Contact:
      catherine.barriere@uca.fr. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29069307
TI  - Effects of Thiamethoxam-Treated Seed on Mexican Bean Beetle (Coleoptera:
      Coccinellidae), Nontarget Arthropods, and Crop Performance in Southwestern
      Virginia Snap Beans.
AB  - Thiamethoxam is a neonicotinoid insecticide commonly applied directly to the
      seeds (seed-treatment) of commercial snap beans, Phaseolus vulgaris L. While
      previous studies have examined target and nontarget effects of thiamethoxam seed
      treatments in snap beans and other crops, to our knowledge, none have been
      conducted in agroecosystems predominated by the pest Mexican bean beetle,
      Epilachna varivestis Mulsant (Coleoptera: Coccinellidae). This study examined the
      effects of thiamethoxam-treated snap beans on E. varivestis, other arthropods,
      and crop performance in southwestern Virginia. Greenhouse experiments were
      conducted to evaluate residual toxicity of treated snap beans to E. varivestis
      and a key predator, Podisus maculiventris (Say) (Hemiptera: Pentatomidae).
      Treated plants were highly toxic to E. varivestis at 13 d, moderately toxic from
      16 to 20 d, and minimally toxic at 24 d. P. maculiventris was unaffected by
      exposure to treated plants or by feeding on E. varivestis that consumed treated
      plants. Small plot field experiments in 2014 and 2015 showed no significant
      effects of thiamethoxam seed-treatments on E. varivestis densities, other
      arthropods, crop injury, or yield. In 2016, planting was delayed by persistent
      rain, resulting in early E. varivestis colonization. In this year, thiamethoxam
      treated plants had significantly lower densities and feeding injury from E.
      varivestis, followed by significantly higher yields. Natural enemies were
      unaffected by seed-treatments in all field experiments. These experiments
      demonstrated that thiamethoxam seed-treatments provide control of E. varivestis
      when beetles infest fields within 2 to 3 wk after planting; but otherwise provide
      negligible advantages. Negative effects from thiamethoxam seed-treatments on
      nontarget arthropods appear minimal for snap beans in this region.

PMID- 29069304
TI  - Estradiol-Dependent Stimulation and Suppression of Gonadotropin-Releasing Hormone
      Neuron Firing Activity by Corticotropin-Releasing Hormone in Female Mice.
AB  - Gonadotropin-releasing hormone (GnRH) neurons are the final central regulators of
      reproduction, integrating various inputs that modulate fertility. Stress
      typically inhibits reproduction but can be stimulatory; stress effects can also
      be modulated by steroid milieu. Corticotropin-releasing hormone (CRH) released
      during the stress response may suppress reproduction independent of downstream
      glucocorticoids. We hypothesized CRH suppresses fertility by decreasing GnRH
      neuron firing activity. To test this, mice were ovariectomized (OVX) and either
      implanted with an estradiol capsule (OVX+E) or not treated further to examine the
      influence of estradiol on GnRH neuron response to CRH. Targeted extracellular
      recordings were used to record firing activity from green fluorescent protein
      identified GnRH neurons in brain slices before and during CRH treatment;
      recordings were done in the afternoon when estradiol has a positive feedback
      effect to increase GnRH neuron firing. In OVX mice, CRH did not affect the firing
      rate of GnRH neurons. In contrast, CRH exhibited dose-dependent stimulatory (30
      nM) or inhibitory (100 nM) effects on GnRH neuron firing activity in OVX+E mice;
      both effects were reversible. The dose-dependent effects of CRH appear to result
      from activation of different receptor populations; a CRH receptor type-1 agonist
      increased firing activity in GnRH neurons, whereas a CRH receptor type-2 agonist
      decreased firing activity. CRH and specific agonists also differentially
      regulated short-term burst frequency and burst properties, including burst
      duration, spikes/burst, and/or intraburst interval. These results indicate that
      CRH alters GnRH neuron activity and that estradiol is required for CRH to exert
      both stimulatory and inhibitory effects on GnRH neurons.

PMID- 29069309
TI  - Vegetation Management and Host Density Influence Bee-Parasite Interactions in
      Urban Gardens.
AB  - Apocephalus borealis phorid flies, a parasitoid of bumble bees and yellow jacket
      wasps in North America, was recently reported as a novel parasitoid of the honey
      bee Apis mellifera Linnaeus (Hymenoptera: Apidae). Little is known about the
      ecology of this interaction, including phorid fecundity on bee hosts, whether
      phorid-bee parasitism is density dependent, and which local habitat and landscape
      features may correlate with changes in parasitism rates for either bumble or
      honey bees. We examined the impact of local and landscape drivers and host
      abundance on phorid parasitism of A. mellifera and the bumble bee Bombus
      vosnesenskii Radoszkowski (Hymenoptera: Apidae). We worked in 19 urban gardens
      along the North-Central Coast of California, where phorid parasitism of honey
      bees was first reported in 2012. We collected and incubated bees for phorid
      emergence, and surveyed local vegetation, ground cover, and floral
      characteristics as well as land cover types surrounding gardens. We found that
      phorid parasitism was higher on bumble bees than on honey bees, and phorids
      produced nearly twice as many pupae on individual bumble bee hosts than on honey
      bee hosts. Parasitism of both bumble and honey bees increased with abundance of
      honey bees in a site. Differences in landscape surroundings did not correlate
      with parasitism, but local factors related to bee resource provisioning (e.g.,
      tree and shrub abundance) positively correlated with increased parasitism. This
      research thus helps to document and describe conditions that may have facilitated
      phorid fly host shift to honey bees and further elucidate how resource
      provisioning in urban gardens influences bee-parasite interactions.

PMID- 29069310
TI  - mORCA: sailing bioinformatics world with mobile devices.
AB  - Motivation: Nearly 10 years have passed since the first mobile apps appeared.
      Given the fact that bioinformatics is a web-based world and that mobile devices
      are endowed with web-browsers, it seemed natural that bioinformatics would
      transit from personal computers to mobile devices but nothing could be further
      from the truth. The transition demands new paradigms, designs and novel
      implementations. Results: Throughout an in-depth analysis of requirements of
      existing bioinformatics applications we designed and deployed an easy-to-use web
      based lightweight mobile client. Such client is able to browse, select, compose
      automatically interface parameters, invoke services and monitor the execution of
      Web Services using the service's metadata stored in catalogs or repositories.
      Availability and implementation: mORCA is available at http://bitlab
      es.com/morca/app as a web-app. It is also available in the App store by Apple and
      Play Store by Google. The software will be available for at least 2 years.
      Contact: ortrelles@uma.es. Supplementary information: Source code, final web-app,
      training material and documentation is available at http://bitlab-es.com/morca.

PMID- 29069311
TI  - Interaction of Insecticide and Media Moisture on Ambrosia Beetle (Coleoptera:
      Curculionidae) Attacks on Selected Ornamental Trees.
AB  - Exotic ambrosia beetles, particularly Xylosandrus crassiusculus (Motschulsky)
      (Coleoptera: Curculionidae: Scolytinae) and Xylosandrus germanus (Blandford)
      (Coleoptera: Curculionidae: Scolytinae), are among the most damaging pests of
      ornamental trees in nurseries. Growers have had few tactics besides insecticide
      applications to reduce ambrosia beetle attacks but recent research has shown that
      attacks may be reduced by maintaining media moisture below a 50% threshold
      thereby reducing flood stress. We compared the efficacy of managing media
      moisture and insecticide applications for reducing ambrosia beetle attacks on
      three ornamental tree species in North Carolina. During trials in spring 2013 and
      2015, flooded Cornus florida and Cornus kousa were heavily attacked despite
      sprays with permethrin, but nonflooded C. kousa or C. florida were not attacked.
      In spring 2015 trials, both nonflooded and flooded Styrax japonicus were heavily
      attacked regardless of permethrin applications. Although ethanol emissions were
      not measured, the apparently healthy nonflooded S. japonicus trees may have been
      exposed to an unknown physiological stress, such as low temperature injury, the
      previous winter, which predisposed them to beetle attack. However, ethanol levels
      within host tissues were not measured as part of the current study. X.
      crassiusculus (75%), Xyloborinus saxesenii Ratzburg (13%), and X. germanus (9%)
      were the most abundant species collected in ethanol baited traps deployed in
      2015, while X. crassiusculus (63%) and X. germanus (36%) were the predominant
      species reared from attacked trees. Results indicate that managing media moisture
      levels at or below 50%, and maximizing tree health overall, may provide
      significant protection against Xylosandrus spp. attacks in flood intolerant tree
      species.

PMID- 29069312
TI  - PESTO: Parameter EStimation TOolbox.
AB  - Summary: PESTO is a widely applicable and highly customizable toolbox for
      parameter estimation in MathWorks MATLAB. It offers scalable algorithms for
      optimization, uncertainty and identifiability analysis, which work in a very
      generic manner, treating the objective function as a black box. Hence, PESTO can
      be used for any parameter estimation problem, for which the user can provide a
      deterministic objective function in MATLAB. Availability and implementation:
      PESTO is a MATLAB toolbox, freely available under the BSD license. The source
      code, along with extensive documentation and example code, can be downloaded from
      https://github.com/ICB-DCM/PESTO/. Contact: jan.hasenauer@helmholtz-muenchen.de.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29069313
TI  - Developmental Phase-Specific Mortality After Ultraviolet-B Radiation Exposure in
      the Two-Spotted Spider Mite.
AB  - Exposure to ambient ultraviolet-B (UVB) radiation generates DNA lesions, such as
      cyclobutane pyrimidine dimers and 6-4 pyrimidine-pyrimidine photoproducts in
      Tetranychus urticae Koch (Acari: Tetranychidae). Larvae appeared normal and
      healthy after UVB irradiation. Conversely, many mites were trapped in their old
      epidermis or experienced retarded development and shrunk, thus failing to molt
      from protochrysalises to protonymphs and died. This suggested that DNA lesions
      per se were not causing lethality in mites unless damaged genes were expressed.
      UVB-induced DNA lesions may have interfered with DNA replication and gene
      expression during the physiological changes of morphogenesis in the chrysalis
      stage. Comprehensive gene expression analysis by RNA sequencing revealed that
      gene expression involving epidermal tissue (characteristically cuticular protein
      genes) and myosin heavy chain muscle-like genes were downregulated in
      protochrysalises irradiated with UVB at the larval stage. We conclude that the
      success of protochrysalis molting is determined by whether the DNA lesions of
      genes, particularly those connected with morphogenesis, are repaired before
      expression at the protochrysalis stage.

PMID- 29069314
TI  - Evaluation of tools for long read RNA-seq splice-aware alignment.
AB  - Motivation: High-throughput sequencing has transformed the study of gene
      expression levels through RNA-seq, a technique that is now routinely used by
      various fields, such as genetic research or diagnostics. The advent of third
      generation sequencing technologies providing significantly longer reads opens up
      new possibilities. However, the high error rates common to these technologies set
      new bioinformatics challenges for the gapped alignment of reads to their genomic
      origin. In this study, we have explored how currently available RNA-seq splice
      aware alignment tools cope with increased read lengths and error rates. All
      tested tools were initially developed for short NGS reads, but some have claimed
      support for long Pacific Biosciences (PacBio) or even Oxford Nanopore
      Technologies (ONT) MinION reads. Results: The tools were tested on synthetic and
      real datasets from two technologies (PacBio and ONT MinION). Alignment quality
      and resource usage were compared across different aligners. The effect of error
      correction of long reads was explored, both using self-correction and correction
      with an external short reads dataset. A tool was developed for evaluating RNA-seq
      alignment results. This tool can be used to compare the alignment of simulated
      reads to their genomic origin, or to compare the alignment of real reads to a set
      of annotated transcripts. Our tests show that while some RNA-seq aligners were
      unable to cope with long error-prone reads, others produced overall good results.
      We further show that alignment accuracy can be improved using error-corrected
      reads. Availability and implementation:
      https://github.com/kkrizanovic/RNAseqEval,
      https://figshare.com/projects/RNAseq_benchmark/24391. Contact: mile.sikic@fer.hr.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29069316
TI  - Retinal microvascular dysfunction in heart failure.
AB  - Aims: Retinal vessel analysis (RVA) represents a novel, non-invasive, and
      reliable method to study the microcirculation in the eye. The goal of this study
      was to assess the extent of retinal microvascular dysfunction in patients with
      chronic heart failure (CHF) compared to controls and established measures of
      vascular function. Methods and results: In this prospective, single-centre,
      observational study, 74 patients with compensated CHF (mean age 63.5 +/- 11.2
      years, 32% female, mean left-ventricular ejection fraction 37 +/- 12.8%), 74
      patients with cardiovascular risk factors (CVRF; 64.1 +/- 12.7 years, 34%
      female), and 74 healthy controls (HC; 57.8 +/- 14.2 years, 35% female) were
      included. The primary endpoint, flicker-induced dilatation of retinal arterioles
      (FIDart), was significantly reduced in patients with CHF compared to CVRF and HC
      (mean FIDart 0.9 +/-  0.2 vs. 2.3 +/- 0.3 and vs. 3.6 +/- 0.3%, respectively,
      both P < 0.001 before and after propensity score-weighted analysis). Similar
      differences were seen for venular FID. FIDart was less impaired in patients with
      dilated compared to ischaemic cardiomyopathy. No significant differences were
      observed for arteriovenous ratio and flow-mediated dilatation. Impaired FIDven
      was associated with echocardiographically estimated systolic pulmonary artery
      pressure and left atrial volume index. Conclusion: Retinal microvascular
      dilatation in response to flicker light is impaired in CHF. RVA may represent a
      new and useful method to non-invasively monitor microvascular abnormalities in
      heart failure in an easy and standardized way without the use of radiation.

PMID- 29069315
TI  - The Impact of Pneumococcal Vaccination on Bacterial and Viral Pneumonia in
      Western Australian Children: Record Linkage Cohort Study of 469589 Births, 1996
      2012.
AB  - Background: Pneumococcal conjugate vaccine (PCV) was included in Australia's
      National Immunisation Program for all children from 2005. We assessed the impact
      of PCV on all-cause and pathogen-specific pneumonia hospitalizations in Western
      Australian (WA) children aged <=16 years. Methods: All hospitalizations with
      pneumonia-related International Statistical Classification of Diseases and
      Related Health Problems, Tenth Revision, Australian Modification diagnosis codes
      occurring in WA-born children (1996-2012) were linked to pathology records. Age
      specific incidence rate ratios and temporal trends for all-cause and pathogen
      specific pneumonia hospitalizations were calculated before and after PCV
      introduction. Results: Among 469589 births, there were 15175 pneumonia-related
      hospitalizations. Hospitalization rates were 6.7 (95% confidence interval, 6.4
      6.9) times higher in Aboriginal than in non-Aboriginal children. Following PCV
      introduction, all-cause pneumonia hospitalizations showed significant declines
      across all age groups. A pathogen was identified in 2785 of 6693 (41.6%)
      pneumonia hospitalizations that linked to a pathology record. Respiratory
      syncytial virus (RSV) was most frequently identified, with RSV-associated
      pneumonia hospitalization rates of 89.6/100000 child-years in Aboriginal and
      26.6/100000 child-years in non-Aboriginal children. The most common bacterial
      pathogen was Streptococcus pneumoniae in Aboriginal children (32.9/100000 child
      years) and Mycoplasma pneumoniae in non-Aboriginal children (8.4/100000 child
      years). Viral pneumonia rates declined in all children following PCV
      introduction, with the greatest declines seen in non-Aboriginal children;
      declines in bacterial pneumonia were observed in non-Aboriginal children.
      Conclusions: Based on our ecological analyses, PCV seems to have had an impact on
      hospitalizations for pneumonia, suggesting that the pneumococcus is likely to
      play a role in both bacterial and viral pneumonia. Respiratory viruses remain an
      important pathogen in childhood pneumonia. Vaccines targeting respiratory viruses
      are needed to combat the residual burden of childhood pneumonia.

PMID- 29069317
TI  - Constructing prediction models from expression profiles for large scale lncRNA
      miRNA interaction profiling.
AB  - Motivation: The interaction of miRNA and lncRNA is known to be important for gene
      regulations. However, not many computational approaches have been developed to
      analyze known interactions and predict the unknown ones. Given that there are now
      more evidences that suggest that lncRNA-miRNA interactions are closely related to
      their relative expression levels in the form of a titration mechanism, we
      analyzed the patterns in large-scale expression profiles of known lncRNA-miRNA
      interactions. From these uncovered patterns, we noticed that lncRNAs tend to
      interact collaboratively with miRNAs of similar expression profiles, and vice
      versa. Results: By representing known interaction between lncRNA and miRNA as a
      bipartite graph, we propose here a technique, called EPLMI, to construct a
      prediction model from such a graph. EPLMI performs its tasks based on the
      assumption that lncRNAs that are highly similar to each other tend to have
      similar interaction or non-interaction patterns with miRNAs and vice versa. The
      effectiveness of the prediction model so constructed has been evaluated using the
      latest dataset of lncRNA-miRNA interactions. The results show that the prediction
      model can achieve AUCs of 0.8522 and 0.8447 +/- 0.0017 based on leave-one-out
      cross validation and 5-fold cross validation. Using this model, we show that
      lncRNA-miRNA interactions can be reliably predicted. We also show that we can use
      it to select the most likely lncRNA targets that specific miRNAs would interact
      with. We believe that the prediction models discovered by EPLMI can yield great
      insights for further research on ceRNA regulation network. To the best of our
      knowledge, EPLMI is the first technique that is developed for large-scale lncRNA
      miRNA interaction profiling. Availability and implementation: Matlab codes and
      dataset are available at https://github.com/yahuang1991polyu/EPLMI/. Contact: yu
      an.huang@connect.polyu.hk or zhuhongyou@ms.xjb.ac.cn. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29069320
TI  - Breast Implant Q Fever as a Source of In-Hospital Transmission.
AB  - Herein, we describe the first case of mammary implant infection caused by
      Coxiella burnetii, resulting in delayed diagnosis and treatment and an in
      hospital cross-transmission of Q fever to medical personnel.

PMID- 29069318
TI  - Bartender: a fast and accurate clustering algorithm to count barcode reads.
AB  - Motivation: Barcode sequencing (bar-seq) is a high-throughput, and cost effective
      method to assay large numbers of cell lineages or genotypes in complex cell
      pools. Because of its advantages, applications for bar-seq are quickly growing
      from using neutral random barcodes to study the evolution of microbes or cancer,
      to using pseudo-barcodes, such as shRNAs or sgRNAs to simultaneously screen large
      numbers of cell perturbations. However, the computational pipelines for bar-seq
      clustering are not well developed. Available methods often yield a high frequency
      of under-clustering artifacts that result in spurious barcodes, or over
      clustering artifacts that group distinct barcodes together. Here, we developed
      Bartender, an accurate clustering algorithm to detect barcodes and their
      abundances from raw next-generation sequencing data. Results: In contrast with
      existing methods that cluster based on sequence similarity alone, Bartender uses
      a modified two-sample proportion test that also considers cluster size. This
      modification results in higher accuracy and lower rates of under- and over
      clustering artifacts. Additionally, Bartender includes unique molecular
      identifier handling and a 'multiple time point' mode that matches barcode
      clusters between different clustering runs for seamless handling of time course
      data. Bartender is a set of simple-to-use command line tools that can be
      performed on a laptop at comparable run times to existing methods. Availability
      and implementation: Bartender is available at no charge for non-commercial use at
      https://github.com/LaoZZZZZ/bartender-1.1. Contact: sasha.levy@stonybrook.edu or
      song.wu@stonybrook.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29069319
TI  - Sex-specific associations of different anthropometric indices with acute and
      chronic insomnia.
AB  - Background: Sleep disorders, including insomnia, are risk factors for weight
      gain. However, few epidemiological studies have investigated the association of
      anthropometric markers with insomnia as an outcome. Methods: In this
      observational, cross-sectional study, we assessed the association of 3 different
      anthropometric indices with acute and chronic insomnia. We used data from 13 389
      French adults (mean age= 51.9 +/- 13.1 years; 70.3% women) enrolled in the
      NutriNet-Sante-Biobank cohort. Body weight, height, waist and hip circumference
      were measured once during a clinic visit (2011-14). Body mass index (BMI), waist
      circumference (WC) and waist-to-hip ratio (WHR) were the main predictors. Acute
      (past 8 days) and chronic (>=3 months) insomnia were assessed in 2014 via a self
      report questionnaire. We fit multivariable logistic regression models providing
      odds ratios (OR) and 95% confidence intervals (CI). Results: Overweight (25.0 <=
      BMI < 30.0 kg/m2) and general obesity (BMI >= 30.0 kg/m2) appeared to have an
      inverse association with acute insomnia only among men (overweight: OR= 0.80, 95%
      CI: 0.70, 0.92; obesity: OR= 0.78, 95% CI: 0.63, 0.98). Obesity assessed by BMI
      and WHR appeared to be positively associated with chronic insomnia only among
      women (BMI: OR= 1.23, 95% CI: 1.04, 1.45; WHR: OR= 2.24, 95% CI: 1.07, 4.72). WC
      did not display any significant associations in either sex. Conclusions: These
      cross-sectional results revealed sex-specific associations of overweight/obesity
      with different types of insomnia, and merit confirmation longitudinally with
      objectively assessed sleep parameters. Nonetheless, the findings reinforce the
      critical importance of joint health behaviour promotion.

PMID- 29069321
TI  - Influenza and pneumococcal vaccination in older adults living in nursing home: a
      survival analysis on the shelter study.
AB  - Background: Influenza and pneumococcal vaccines have been proved to be effective
      and safe in preventing and controlling infection among elderly, reducing
      morbidity and mortality. However, some evidences raised health concerns related
      to these vaccinations. This study aims to identify prevalence and outcomes
      related to influenza and pneumococcal vaccinations in a large European population
      of frail old people living in nursing homes (NHs). Methods: We conducted a
      survival analysis of NH residents participating to the Services and Health for
      Elderly in Long-TERm project, a prospective cohort study collecting information
      on residents admitted to 57 NH in eight countries (Czech Republic, England,
      Finland, France, Germany, Italy, The Netherlands and Israel). Clinical and
      demographical data were collected using the international resident assessement
      instrument for long-term care facilities. Incident mortality was recorded during
      1-year follow-up. A shared-frailty Cox regression model was used to assess the
      impact of vaccination status on mortality. Results: Mean age of 3510 participants
      was 84.6 years (SD = 7.7). In total, 81.7 and 27.0% received influenza and
      pneumococcal vaccination, respectively. Overall, 727 (20.7%) residents died
      during the follow-up period. After adjusting for potential confounders, which
      included age, sex, number of diseases, depression, cognitive and functional
      status, influenza (HR = 0.80; 95% CI 0.66-0.97) and the combination of influenza
      and pneumococcal vaccination (HR = 0.72; 95% CI 0.57-0.91), but not pneumococcal
      vaccination alone (HR = 0.52; 95% CI 0.25-1.06), were associated with a
      statistically significant reduction in mortality in respect of no vaccinations.
      Conclusion: In a population of older adult living in NH influenza and the
      combination of influenza and pneumococcal vaccination were associated with a
      reduction in all-cause mortality respect to no vaccination.

PMID- 29069322
TI  - Rapid Determination of Non-steroidal Anti-inflammatory Drugs in Aquatic Matrices
      by Two-phase Micro-electrodriven Membrane Extraction Combined with Liquid
      Chromatography.
AB  - Two-phase micro-electrodriven membrane extraction (EME) procedure for the pre
      concentration of selected non-steroidal anti-inflammatory drugs (NSAIDs) in
      aquatic matrices was investigated. Agarose film was used as interface between
      donor and acceptor phase in EME which allowed for selective extraction of the
      analytes prior to high performance liquid chromatography-ultraviolet detection.
      Charged analytes were transported from basic aqueous sample solution through
      agarose film into 1-octanol as an acceptor phase at 9 V potential. Response
      surface methodology in conjunction with the central composite design showed good
      correlations between extraction time and applied voltage (R2 > 0.9358). Under
      optimized extraction conditions, the method showed good linearity in the
      concentration range of 0.5-500 MUg L-1 with coefficients of determination, r2>=
      0.9942 and good limits of detection (0.14-0.42 MUg L-1) and limits of
      quantification (0.52-1.21 MUg L-1). The results also showed high enrichment
      factors (62-86) and good relative recoveries (72-114%) with acceptable
      reproducibilities (RSDs <= 7.5% n = 3). The method was successfully applied to
      the determination of NSAIDs from tap water and river water samples. The proposed
      method proved to be rapid, simple and requires low voltage and minute amounts of
      organic solvent, thus environmentally friendly.

PMID- 29069323
TI  - Salmonella enterica Serotype 4,[5],12:i:- in Swine in the United States Midwest:
      An Emerging Multidrug-Resistant Clade.
AB  - Background: Salmonella 4,[5],12:i:-, a worldwide emerging pathogen that causes
      many food-borne outbreaks mostly attributed to pig and pig products, is expanding
      in the United States. Methods: Whole-genome sequencing was applied to conduct
      multiple comparisons of 659 S. 4,[5],12:i:- and 325 Salmonella Typhimurium from
      different sources and locations (ie, the United States and Europe) to assess
      their genetic heterogeneity, with a focus on strains recovered from swine in the
      US Midwest. In addition, the presence of resistance genes and other virulence
      factors was detected and the antimicrobial resistance phenotypes of 50 and 22
      isolates of livestock and human origin, respectively, was determined. Results:
      The S. 4,5,12:i:- strains formed two main clades regardless of their source and
      geographic origin. Most (84%) of the US isolates recovered in 2014-2016,
      including those (48 of 51) recovered from swine in the US Midwest, were part of
      an emerging clade. In this clade, multiple genotypic resistance determinants were
      predominant, including resistance against ampicillin, streptomycin, sulfonamides,
      and tetracyclines. Phenotypic resistance to enrofloxacin (11 of 50) and ceftiofur
      (9 of 50) was found in conjunction with the presence of plasmid-mediated
      resistance genes (qnrB19/qnrB2/qnrS1 and blaCMY-2/blaSHV-12, respectively).
      Higher similarity was also found between S. 4,[5],12:i:- from the emerging clade
      and S. Typhimurium from Europe than with S. Typhimurium from the United States.
      Conclusions: Salmonella 4,[5],12:i:- currently circulating in swine in the US
      Midwest are likely to be part of an emerging multidrug-resistant clade first
      reported in Europe, and can carry plasmid-mediated resistance genes that may be
      transmitted horizontally to other bacteria, and thus may represent a public
      health concern.

PMID- 29069325
TI  - Serial changes in the side-branch ostial area after main-vessel stenting with
      kissing balloon inflation for coronary bifurcation lesions, assessed by 3D
      optical coherence tomography.
AB  - Aims: We evaluated the influence of the jailing configuration and guidewire
      rewiring position in front of the side-branch (SB) ostium before kissing balloon
      inflation (KBI) against side-branch ostial area (SBOA) at follow-up using 3D
      optical coherence tomography (3D-OCT). Methods and results: We retrospectively
      analysed the cases of the 37 consecutive patients who underwent main-vessel (MV)
      stenting with KBI for coronary bifurcation lesion under OCT guidance and the
      follow-up OCT 6-12 months. We divided the patients into two groups, considering
      both the jailing configuration and the rewiring position by 3D-OCT. We defined
      the cases that achieved both the distal rewiring and link-free carina
      configuration as the FCD group, and the other cases were defined as the Non-FCD
      group. We compared the differences in the SBOA derived by the cut-plane analysis
      and the number of compartments between the two groups. The median and
      interquartile range of serial change and percent serial change in SBOA in the FCD
      group were significantly larger than those in the Non-FCD group [0.43 mm2 (-0.29
      to 0.91) vs. -0.65 mm2 (-1.33 to 0.34); P = 0.0136 and 9.47% (-8.37 to 27.33) vs.
      -13.77% (-31.64 to 10.88); P = 0.0182]. Conclusion: This serial OCT study
      demonstrated that the achievement of both the distal rewiring and link-free
      carina configuration may be important for the preservation of the SBOA after MV
      stenting with KBI for coronary bifurcation lesions.

PMID- 29069324
TI  - Activity in LIP, But not V4, Matches Performance When Attention is Spread.
AB  - The enhancement of neuronal responses in many visual areas while animals perform
      spatial attention tasks has widely been thought to be the neural correlate of
      visual attention, but it is unclear whether the presence or absence of this
      modulation contributes to our striking inability to notice changes in change
      blindness examples. We asked whether neuronal responses in visual area V4 and the
      lateral intraparietal area (LIP) in posterior parietal cortex could explain the
      limited ability of subjects to attend multiple items in a display. We trained
      animals to perform a change detection task in which they had to compare 2 arrays
      of stimuli separated briefly in time and found that each animal's performance
      decreased as function of set-size. Neuronal discriminability in V4 was consistent
      across set-sizes, but decreased for higher set-sizes in LIP. The introduction of
      a reward bias produced attentional enhancement in V4, but this could not explain
      the vast improvement in performance, whereas the enhancement in LIP responses
      could. We suggest that behavioral set-size effects and the marked improvement in
      performance with focused attention may not be related to response enhancement in
      V4 but, instead, may occur in or on the way to LIP.

PMID- 29069326
TI  - A Rapid and Simple HPLC Method for Therapeutic Monitoring of Vancomycin.
AB  - Therapeutic monitoring of the antibiotic vancomycin is important to achieve
      specific plasma concentration and prevent toxic effects. Several assays have been
      described for vancomycin determination in clinical practice, but high-performance
      liquid chromatography is still considered the gold standard for the
      quantification of vancomycin. In this study, we developed a new and rapid high
      performance liquid chromatography method requiring 50 MUL of plasma for the
      quantification of vancomycin. Acetonitrile was used for processing plasma by
      protein precipitation (1:2.5). Isocratic chromatographic analysis was carried out
      on a C18 silica-based (2.7 MUm) column with the mobile phase containing 20 mM
      ammonium acetate/formic acid buffer (pH 4.0):methanol 88:12 (v/v). A diode array
      detector was used for UV detection at 240 nm. This method was validated according
      to the Brazilian Health Surveillance Agency legislation and International
      Conference on Harmonization guidelines. The measurement range was 1-100 MUg/mL,
      analysis time was 8 min, and intermediate precision was <12%, supporting the
      present method as a fast, simple, and effective alternative for therapeutic
      monitoring of vancomycin.

PMID- 29069327
TI  - The role of complement inhibition in kidney transplantation.
AB  - Introduction and background: The complement system which belongs to the innate
      immune system acts both as a first line of defence against various pathogens and
      as a guardian of host homeostasis. The role of complement has been recently
      highlighted in several aspects of kidney transplantation: ischaemia-reperfusion,
      antibody-mediated rejection and native kidney disease recurrence. Sources of
      data: Experimental data, availability of complement-blocking molecules (mainly
      the anti-C5 monoclonal antibody, eculizumab) and several trials in human kidney
      transplant recipients has led to some areas of agreement and some disappointment.
      Areas of agreement and controversies: So far, eculizumab has shown great efficacy
      in treatment and prevention of atypical haemolytic and uraemic syndrome, some
      efficacy in the prevention of antibody-mediated and so far no efficacy in the
      prevention of delayed graft function. Growing points: Among the numerous
      potentially available drugs potentially interfering with complement, recent focus
      has been made on C1 blockers in the setting of antibody-mediated rejection with
      promising results. Areas timely for developing research: Complement is now
      recognized as a major player in transplant immunology, several targets are going
      to be tested to define precisely which ones may be potentially useful in clinical
      practice.

PMID- 29069328
TI  - The Relationship Between Latent Tuberculosis Infection and Acute Myocardial
      Infarction.
AB  - Background: Tuberculosis has been associated with an increased risk of
      cardiovascular disease (CVD), including acute myocardial infarction (AMI). We
      investigated whether latent tuberculosis infection (LTBI) is associated with AMI.
      Methods: We conducted a case-control study in 2 large national public hospital
      networks in Lima, Peru, between July 2015 and March 2017. Case patients were
      patients with a first time diagnosis of type 1 (spontaneous) AMI. Controls were
      patients without a history of AMI. We excluded patients with known human
      immunodeficiency virus infection, tuberculosis disease, or prior LTBI treatment.
      We used the QuantiFERON-TB Gold In-Tube assay to identify LTBI. We used logistic
      regression modeling to estimate the odds ratio (OR) of LTBI in AMI case patients
      versus non-AMI controls. Results: We enrolled 105 AMI case patients and 110 non
      AMI controls during the study period. Overall, the median age was 62 years
      (interquartile range, 56-70 years); 69% of patients were male; 64% had
      hypertension, 40% dyslipidemia, and 39% diabetes mellitus; 30% used tobacco; and
      24% were obese. AMI case patients were more likely than controls to be male (80%
      vs 59%; P < .01) and tobacco users (41% vs 20%; P < .01). LTBI was more frequent
      in AMI case patients than in controls (64% vs 49% [P = .03]; OR, 1.86; 95%
      confidence interval [CI], 1.08-3.22). After adjustment for age, sex,
      hypertension, dyslipidemia, diabetes mellitus, tobacco use, obesity, and family
      history of coronary artery disease, LTBI remained independently associated with
      AMI (adjusted OR, 1.90; 95% CI, 1.05-3.45). Conclusions: LTBI was independently
      associated with AMI. Our results suggest a potentially important role of LTBI in
      CVD.

PMID- 29069329
TI  - Potential for plant biocontrol activity of isolated Pseudomonas aeruginosa and
      Bacillus stratosphericus strains against bacterial pathogens acting through both
      induced plant resistance and direct antagonism.
AB  - Phytopathogenic bacteria have caused significant damage to agricultural crops in
      both controlled and open cultivation practices, imposing heavy losses to farmers.
      Thereby, the goal of this study was to evaluate Pseudomonas aeruginosa and
      Bacillus stratosphericus isolated from soil has antagonistic activity against
      bacterial phytopathogens with the potential to control plant diseases. Isolated
      novel strains of P. aeruginosa and B. stratosphericus showed broad spectrum of
      antagonistic activity against five bacterial phytopathogens. Antagonistic
      activity was examined under optimized pH (8 and 7), carbon sources (lactose and
      starch), nitrogen sources (ammonium chloride, peptone and ammonium nitrate) for
      P. aeruginosa and B. stratosphericus, respectively, and biocatalyst production
      (chitinase, protease and amylase) was studied. Additionally, up-regulation of
      defense-related genes (PR-1a and PAL) was studied in tomato plants treated with
      P. aeruginosa and B. stratosphericus. The induction of defense-related genes in
      tomato plant was triggered after 12 h treatment with a cell concentration of 0.20
      O.D. for P. aeruginosa and 0.21 O.D. for B. stratosphericus during treatment
      period. Broad spectrum antagonistic activity was observed due to antibiotic and
      siderophore production by P. aeruginosa and B. stratosphericus.

PMID- 29069330
TI  - DISC: DISulfide linkage Characterization from tandem mass spectra.
AB  - Motivation: Enzymatic digestion under appropriate reducing conditions followed by
      mass spectrometry analysis has emerged as the primary method for disulfide bond
      analysis. The large amount of mass spectral data collected in the mass
      spectrometry experiment requires effective computational approaches to automate
      the interpretation process. Although different approaches have been developed for
      such purpose, they always choose to ignore the frequently observed internal ion
      fragments and they lack a reasonable quality control strategy and calibrated
      scoring scheme for the statistical validation and ranking of the reported
      results. Results: In this research, we present a new computational approach, DISC
      (DISulfide bond Characterization), for matching an input MS/MS spectrum against
      the putative disulfide linkage structures hypothetically constructed from the
      protein database. More specifically, we consider different ion types including a
      variety of internal ions that frequently observed in mass spectra resulted from
      disulfide linked peptides, and introduce an effective two-layer scoring scheme to
      evaluate the significance of the matching between spectrum and structure, based
      on which we have also developed a useful target-decoy strategy for providing
      quality control and reporting false discovery rate in the final results.
      Systematic experiments conducted on both low-complexity and high-complexity
      datasets demonstrated the efficiency of our proposed method for the
      identification of disulfide bonds from MS/MS spectra, and showed its potential in
      characterizing disulfide bonds at the proteome scale instead of just a single
      protein. Availability and implementation: Software is available for downloading
      at http://www.csd.uwo.ca/yliu766/. Contact: yliu766@uwo.ca. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29069331
TI  - Validation of a short-form questionnaire to check patients' adherence to
      antibiotic treatments in an outpatient setting.
AB  - Antimicrobial resistance challenge requests to be able to measure patient
      medication-adherence in outpatient setting, where more than 90% of antibiotics
      are prescribed. We take advantage of an original dataset where adherence to
      treatment has been measured through two alternative measurements: pills count and
      the Morisky scale. Considering the first measure as benchmark, we test the
      validity of each of the Morisky items and their composition in a synthetic scale.
      We show that the short-form version of the medication-adherence scale with three
      items has the best predictive properties in the domain of antibiotic treatments.
      Given its concision, this tool could even be used by clinicians to quickly assess
      patients' adherence and modify it in the course, when needed.

PMID- 29069332
TI  - Sustainable Development Goals (SDGs), and their implementation: A national global
      framework for health, development and equity needs a systems approach at every
      level.
AB  - Introduction: The Sustainable Development Goals (SDGs) are a set of global goals
      for fair and sustainable health at every level: from planetary biosphere to local
      community. The aim is to end poverty, protect the planet and ensure that all
      people enjoy peace and prosperity, now and in the future. Sources of data: The UN
      has established web-sites to inform the implementation of the SDGs and an Inter
      Agency and Expert Group on an Indicator Framework. We have searched for
      independent commentaries and analysis. Areas of agreement: The goals represent a
      framework that is scientifically robust, and widely intuitive intended to build
      upon the progress established by the Millennium Development Goals (MDGs). There
      is a need for system wide strategic planning to integrate the economic, social
      and environmental dimensions into policy and actions. Areas of controversy: Many
      countries have yet to understand the difference between the MDGs and the SDGs,
      particularly their universality, the huge potential of new data methods to help
      with their implementation, and the systems thinking that is needed to deliver the
      vision. The danger is that individual goals may be prioritized without an
      understanding of the potential positive interactions between goals. Growing
      points: There is an increasing understanding that sustainable development needs a
      paradigm shift in our understanding of the interaction between the real economy
      and quality of life. There would be many social, environmental and economic
      benefits in changing our current model. Areas timely for developing research: We
      need to develop systems wide understanding of what supports a healthy environment
      and the art and science of making change.

PMID- 29069333
TI  - Plant-mediated horizontal transmission of Rickettsia endosymbiont between
      different whitefly species.
AB  - A growing number of studies have revealed the presence of closely related
      endosymbionts in phylogenetically distant arthropods, indicating horizontal
      transmission of these bacteria. Here we investigated the interspecific horizontal
      transmission of Rickettsia between two globally invasive whitefly species,
      Bemisia tabaci MEAM1 and B. tabaci MED, via cotton plants. We found both
      scattered and confined distribution patterns of Rickettsia in these whiteflies.
      After entering cotton leaves, Rickettsia was restricted to the leaf phloem
      vessels and could be taken up by both species of the Rickettsia-free whitefly
      adults, but only the scattered pattern was observed in the recipient whiteflies.
      Both the relative quantity of Rickettsia and the efficiency of transmitting
      Rickettsia into cotton leaves were significantly higher in MEAM1 females than in
      MED females. The retention time of Rickettsia transmitted from MEAM1 into cotton
      leaves was at least 5 days longer than that of MED. Phylogenetic analysis based
      on 16S rRNA and gltA genes confirmed that the Rickettsia extracted from the donor
      MEAM1, the cotton leaves, the recipient MEAM1 and the recipient MED were all
      identical. We conclude that cotton plants can mediate horizontal transmission of
      Rickettsia between different insect species, and that the transmission dynamics
      of Rickettsia vary with different host whitefly species.

PMID- 29069334
TI  - Influenza Antiviral Prescribing for Outpatients With an Acute Respiratory Illness
      and at High Risk for Influenza-Associated Complications During 5 Influenza
      Seasons-United States, 2011-2016.
AB  - Background: Influenza causes millions of illnesses annually; certain groups are
      at higher risk for complications. Early antiviral treatment can reduce the risk
      of complications and is recommended for outpatients at increased risk. We
      describe antiviral prescribing among high-risk outpatients for 5 influenza
      seasons and explore factors that may influence prescribing. Methods: We analyzed
      antiviral prescription and clinical data for high-risk outpatients aged >=6
      months with an acute respiratory illness (ARI) and enrolled in the US Influenza
      Vaccine Effectiveness Network during the 2011-2012 through 2015-2016 influenza
      seasons. We obtained clinical information from interviews and electronic medical
      records and tested all enrollees for influenza with real-time reverse
      transcription polymerase chain reaction (rRT-PCR). We calculated the number of
      patients with ARI that must be treated to treat 1 patient with influenza.
      Results: Among high-risk outpatients with ARI who presented to care within 2 days
      of symptom onset (early), 15% (718/4861) were prescribed an antiviral medication,
      including 472 of 1292 (37%) of those with rRT-PCR-confirmed influenza. Forty
      percent of high-risk outpatients with influenza presented to care early. Earlier
      presentation was associated with antiviral treatment (odds ratio [OR], 4.1; 95%
      confidence interval [CI], 3.5-4.8), as was fever (OR, 3.2; 95% CI, 2.7-3.8),
      although 25% of high-risk outpatients with influenza were afebrile. Empiric
      treatment of 4 high-risk outpatients with ARI was needed to treat 1 patient with
      influenza. Conclusions: Influenza antiviral medications were infrequently
      prescribed for high-risk outpatients with ARI who would benefit most. Efforts to
      increase appropriate antiviral prescribing are needed to reduce influenza
      associated complications.

PMID- 29069336
TI  - ArachnoServer 3.0: an online resource for automated discovery, analysis and
      annotation of spider toxins.
AB  - Summary: ArachnoServer is a manually curated database that consolidates
      information on the sequence, structure, function and pharmacology of spider-venom
      toxins. Although spider venoms are complex chemical arsenals, the primary
      constituents are small disulfide-bridged peptides that target neuronal ion
      channels and receptors. Due to their high potency and selectivity, these peptides
      have been developed as pharmacological tools, bioinsecticides and drug leads. A
      new version of ArachnoServer (v3.0) has been developed that includes a
      bioinformatics pipeline for automated detection and analysis of peptide toxin
      transcripts in assembled venom-gland transcriptomes. ArachnoServer v3.0 was
      updated with the latest sequence, structure and functional data, the search-by
      mass feature has been enhanced, and toxin cards provide additional information
      about each mature toxin. Availability and implementation:
      http://arachnoserver.org. Contact: support@arachnoserver.org. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29069335
TI  - Uncovering the wisdom hidden between the lines: the Collaborative Reflexive
      Deliberative Approach.
AB  - Background: Meta-analysis and meta-synthesis have been developed to synthesize
      results across published studies; however, they are still largely grounded in
      what is already published, missing the tacit 'between the lines' knowledge
      generated during many research projects that are not intrinsic to the main
      objectives of studies. Objective: To develop a novel approach to expand and
      deepen meta-syntheses using researchers' experience, tacit knowledge and relevant
      unpublished materials. Methods: We established new collaborations among primary
      health care researchers from different contexts based on common interests in
      reforming primary care service delivery and a diversity of perspectives. Over 2
      years, the team met face-to-face and via tele- and video-conferences to employ
      the Collaborative Reflexive Deliberative Approach (CRDA) to discuss and reflect
      on published and unpublished results from participants' studies to identify new
      patterns and insights. Results: CRDA focuses on uncovering critical insights,
      interpretations hidden within multiple research contexts. For the process to
      work, careful attention must be paid to ensure sufficient diversity among
      participants while also having people who are able to collaborate effectively.
      Ensuring there are enough studies for contextual variation also matters. It is
      necessary to balance rigorous facilitation techniques with the creation of safe
      space for diverse contributions. Conclusions: The CRDA requires large commitments
      of investigator time, the expense of convening facilitated retreats, considerable
      coordination, and strong leadership. The process creates an environment where
      interactions among diverse participants can illuminate hidden information within
      the contexts of studies, effectively enhancing theory development and generating
      new research questions and strategies.

PMID- 29069337
TI  - Health related quality of life and physical activity in prison: a multicenter
      observational study in Italy.
AB  - Background: Inmates have a poorer health status than the general population. The
      physical activity is well know that improve the wellness of the people. This
      multicentric cross-sectional study aimed to assess the relationship between
      Quality of Life (QoL) and physical activity levels among Italian prisoners.
      Methods: Inmates from eight prisons compiled a questionnaire. The Metabolic
      Equivalent of Task (MET) was used to measure inmates' weekly physical activity
      levels (MATwk). Their QoL was measured using two components of Short Form with 12
      items (SF12): MCS (mental score) and PCS (physical score). Results: A total of
      636 questionnaires were compiled. High level of MET was significantly (P <0.05)
      associated with both PCS (OR = 1.02) and MCS (OR = 1.03). The correlations
      between PCS, MCS vs. METwk scores were respectively significant: r = 0.17 and r =
      0.10, P < 0.05. The number of years of detention was associated to higher MET (OR
      = 1.04 P < 0.05). The presence of Physical Exercise Areas (PEAs) within Jails did
      not improve the QoL level. Conclusions: Jails may not seem like the ideal place
      to fight sedentary behavior, but, in any case, health promotion can occur within
      its walls. The heterogeneity of Italian jails, and particularly relative PEAs
      therein (areas had different characteristics between jails), suggests that such
      spaces should be regulated or well defined. Furthermore, the implement of
      training schedules could be done in a standardized way. Despite this
      heterogeneity both the physical and mental components of inmates' quality of life
      were associated to a high level of physical activity.

PMID- 29069338
TI  - Trichomonas vaginalis Brain Abscess in a Neonate.
AB  - We describe a case of cerebral trichomoniasis in a neonate in whom seizures and
      multiorgan failure developed during treatment for staphylococcal sepsis. Brain
      abscesses were identified with cranial sonography, and Trichomonas vaginalis was
      isolated from cerebrospinal fluid samples. The patient died despite metronidazole
      therapy.

PMID- 29069339
TI  - Is Placental Malaria a Long-term Risk Factor for Mild Malaria Attack in Infancy?
      Revisiting a Paradigm.
AB  - Background: Children born to mothers with placental malaria (PM) have been
      described as more susceptible to the occurrence of a first malaria infection.
      However, whether or not these children remain more at risk during infancy has
      never been explored. We aimed to determine if children born to mothers with PM
      are more susceptible to malaria and remain at higher risk between birth and 18
      months. Methods: Five hundred fifty children were followed up weekly with control
      of temperature and, if >37.5 degrees C, both a rapid diagnostic test for malaria
      and a thick blood smear were performed. Taking into account environmental risk of
      infection, the relationship between occurrences of malaria attacks from birth to
      18 months was modeled using Cox models for recurrent events. Results: PM is not
      associated with an overall susceptibility to malaria but only with the delay of
      occurrence of the first malaria attack. Children born from mothers with PM tend
      to have an increased risk for the first malaria attack (hazard ratio [HR] = 1.33;
      P = .048) but not for subsequent ones (HR = 0.9; P = .46). Children who
      experienced 1 malaria attack were strongly at risk to develop subsequent
      infections independent of placental infection and environmental exposure.
      Conclusions: These results are consistent with the existence of an individual
      susceptibility to malaria unrelated to PM. From a public health point of view,
      protecting children born to infected placenta remains a priority, but seems
      insufficient to account for other frail children for whom a biomarker of frailty
      needs to be found.

PMID- 29069340
TI  - In vitro attenuation of a virulent swine isolate of Brachyspira hampsonii.
AB  - Brachyspira hampsonii causes dysentery-like disease in infected pigs. Serial
      passage of a virulent swine isolate (P13) one-hundred times in laboratory culture
      medium was conducted to produce an attenuated strain, and to identify genomic
      determinants of virulence through comparison of genome sequences of the original
      and passaged strains. The resulting strain, P113, did not differ from P13 in
      terms of diagnostic biochemical characteristics but had an enhanced growth rate
      in culture, indicating laboratory adaptation. Whole genome sequencing of P113
      revealed several single-nucleotide changes including a T to C transition that
      results in an R to G amino acid change in a putative mannose-1-phosphate
      guanylytransferase that is implicated in production of lipo-oligosaccharide. P113
      was partially attenuated in a mouse model of infection, indicated by
      significantly fewer observations of abnormal feces in mice infected with P113
      relative to P13. No differences were detected in bacterial shedding in feces,
      demonstrating that the ability of the organism to colonize mice was not affected.
      Passage through a mouse did not further alter the virulence of P113. Results of
      this study provide insight into genomic determinants of virulence in B. hampsonii
      and a live attenuated vaccine candidate.

PMID- 29069341
TI  - Epigenetics and precision medicine in cardiovascular patients: from basic
      concepts to the clinical arena.
AB  - Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide
      and also inflict major burdens on morbidity, quality of life, and societal costs.
      Considering that CVD preventive medications improve vascular outcomes in less
      than half of patients (often relative risk reductions range from 12% to 20%
      compared with placebo), precision medicine offers an attractive approach to
      refine the targeting of CVD medications to responsive individuals in a population
      and thus allocate resources more wisely and effectively. New tools furnished by
      advances in basic science and translational medicine could help achieve this
      goal. This approach could reach beyond the practitioners 'eyeball' assessment or
      venerable markers derived from the physical examination and standard laboratory
      evaluation. Advances in genetics have identified novel pathways and targets that
      operate in numerous diseases, paving the way for 'precision medicine'. Yet the
      inherited genome determines only part of an individual's risk profile. Indeed,
      standard genomic approaches do not take into account the world of regulation of
      gene expression by modifications of the 'epi'genome. Epigenetic modifications
      defined as 'heritable changes to the genome that do not involve changes in DNA
      sequence' have emerged as a new layer of biological regulation in CVD and could
      advance individualized risk assessment as well as devising and deploying tailored
      therapies. This review, therefore, aims to acquaint the cardiovascular community
      with the rapidly advancing and evolving field of epigenetics and its implications
      in cardiovascular precision medicine.

PMID- 29069342
TI  - Holocentric chromosomes: from tolerance to fragmentation to colonization of the
      land.
AB  - Background: The dispersed occurrence of holocentric chromosomes across eukaryotes
      implies they are adaptive, but the conditions under which they confer an
      advantage over monocentric chromosomes remain unclear. Due to their extended
      kinetochore and the attachment of spindle microtubules along their entire length,
      holocentric chromosomes tolerate fragmentation; hence, they may be advantageous
      in times of exposure to factors that cause chromosomal fragmentation
      (clastogens). Scope: It is shown that holocentric organisms may, indeed, thrive
      better than monocentric organisms under clastogenic conditions and that such
      conditions of various duration and intensity have occurred many times throughout
      the history of Earth's biota. One of the most important clastogenic events in
      eukaryotic history, in which holocentric chromosomes may have played the key
      role, was the colonization of land by plants and animals half a billion years
      ago. In addition to arguments supporting the anticlastogenic hypothesis of
      holocentric chromosomes and a discussion of its evolutionary consequences,
      experiments and analyses are proposed to explore this hypothesis in more depth.
      Conclusions: It is argued that the tolerance to clastogens explains the origin of
      holocentric lineages and may also have far-reaching consequences for eukaryotic
      evolution in general as exemplified by the potential role of holocentric
      chromosomes in terrestrialization.

PMID- 29069343
TI  - Job Tasks as Determinants of Thoracic Aerosol Exposure in the Cement Production
      Industry.
AB  - Background: The aims of this study were to identify important determinants and
      investigate the variance components of thoracic aerosol exposure for the workers
      in the production departments of European cement plants. Methods: Personal
      thoracic aerosol measurements and questionnaire information (Noto et al., 2015)
      were the basis for this study. Determinants categorized in three levels were
      selected to describe the exposure relationships separately for the job types
      production, cleaning, maintenance, foreman, administration, laboratory, and other
      jobs by linear mixed models. The influence of plant and job determinants on
      variance components were explored separately and also combined in full models
      (plant&job) against models with no determinants (null). The best mixed models
      (best) describing the exposure for each job type were selected by the lowest
      Akaike information criterion (AIC; Akaike, 1974) after running all possible
      combination of the determinants. Results: Tasks that significantly increased the
      thoracic aerosol exposure above the mean level for production workers were:
      packing and shipping, raw meal, cement and filter cleaning, and de-clogging of
      the cyclones. For maintenance workers, time spent with welding and dismantling
      before repair work increased the exposure while time with electrical maintenance
      and oiling decreased the exposure. Administration work decreased the exposure
      among foremen. A subjective tidiness factor scored by the research team explained
      up to a 3-fold (cleaners) variation in thoracic aerosol levels. Within-worker
      (WW) variance contained a major part of the total variance (35-58%) for all job
      types. Job determinants had little influence on the WW variance (0-4% reduction),
      some influence on the between-plant (BP) variance (from 5% to 39% reduction for
      production, maintenance, and other jobs respectively but an 79% increase for
      foremen) and a substantial influence on the between-worker within-plant variance
      (30-96% for production, foremen, and other workers). Plant determinants had
      little influence on the WW variance (0-2% reduction), some influence on the
      between-worker variance (0-1% reduction and 8% increase), and considerable
      influence on the BP variance (36-58% reduction) compared to the null models.
      Conclusion: Some job tasks contribute to low levels of thoracic aerosol exposure
      and others to higher exposure among cement plant workers. Thus, job task may
      predict exposure in this industry. Dust control measures in the packing and
      shipping departments and in the areas of raw meal and cement handling could
      contribute substantially to reduce the exposure levels. Rotation between low and
      higher exposed tasks may contribute to equalize the exposure levels between high
      and low exposed workers as a temporary solution before more permanent dust
      reduction measures is implemented. A tidy plant may reduce the overall exposure
      for almost all workers no matter of job type.

PMID- 29069344
TI  - DEEPre: sequence-based enzyme EC number prediction by deep learning.
AB  - Motivation: Annotation of enzyme function has a broad range of applications, such
      as metagenomics, industrial biotechnology, and diagnosis of enzyme deficiency
      caused diseases. However, the time and resource required make it prohibitively
      expensive to experimentally determine the function of every enzyme. Therefore,
      computational enzyme function prediction has become increasingly important. In
      this paper, we develop such an approach, determining the enzyme function by
      predicting the Enzyme Commission number. Results: We propose an end-to-end
      feature selection and classification model training approach, as well as an
      automatic and robust feature dimensionality uniformization method, DEEPre, in the
      field of enzyme function prediction. Instead of extracting manually crafted
      features from enzyme sequences, our model takes the raw sequence encoding as
      inputs, extracting convolutional and sequential features from the raw encoding
      based on the classification result to directly improve the prediction
      performance. The thorough cross-fold validation experiments conducted on two
      large-scale datasets show that DEEPre improves the prediction performance over
      the previous state-of-the-art methods. In addition, our server outperforms five
      other servers in determining the main class of enzymes on a separate low-homology
      dataset. Two case studies demonstrate DEEPre's ability to capture the functional
      difference of enzyme isoforms. Availability and implementation: The server could
      be accessed freely at http://www.cbrc.kaust.edu.sa/DEEPre. Contact:
      xin.gao@kaust.edu.sa. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29069347
TI  - VecScreen_plus_taxonomy: imposing a tax(onomy) increase on vector contamination
      screening.
AB  - Motivation: Nucleic acid sequences in public databases should not contain vector
      contamination, but many sequences in GenBank do (or did) contain vectors. The
      National Center for Biotechnology Information uses the program VecScreen to
      screen submitted sequences for contamination. Additional tools are needed to
      distinguish true-positive (contamination) from false-positive (not contamination)
      VecScreen matches. Results: A principal reason for false-positive VecScreen
      matches is that the sequence and the matching vector subsequence originate from
      closely related or identical organisms (for example, both originate in
      Escherichia coli). We collected information on the taxonomy of sources of vector
      segments in the UniVec database used by VecScreen. We used that information in
      two overlapping software pipelines for retrospective analysis of contamination in
      GenBank and for prospective analysis of contamination in new sequence
      submissions. Using the retrospective pipeline, we identified and corrected over
      8000 contaminated sequences in the nonredundant nucleotide database. The
      prospective analysis pipeline has been in production use since April 2017 to
      evaluate some new GenBank submissions. Availability and implementation: Data on
      the sources of UniVec entries were included in release 10.0
      (ftp://ftp.ncbi.nih.gov/pub/UniVec/). The main software is freely available at
      https://github.com/aaschaffer/vecscreen_plus_taxonomy. Contact:
      aschaffe@helix.nih.gov. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29069345
TI  - Adaptive Evolution under Extreme Genetic Drift in Oxidatively Stressed
      Caenorhabditis elegans.
AB  - A mutation-accumulation (MA) experiment with Caenorhabditis elegans nematodes was
      conducted in which replicate, independently evolving lines were initiated from a
      low-fitness mitochondrial electron transport chain mutant, gas-1. The original
      intent of the study was to assess the effect of electron transport chain
      dysfunction involving elevated reactive oxygen species production on patterns of
      spontaneous germline mutation. In contrast to results of standard MA experiments,
      gas-1 MA lines evolved slightly higher mean fitness alongside reduced among-line
      genetic variance compared with their ancestor. Likewise, the gas-1 MA lines
      experienced partial recovery to wildtype reactive oxygen species levels. Whole
      genome sequencing and analysis revealed that the molecular spectrum but not the
      overall rate of nuclear DNA mutation differed from wildtype patterns. Further
      analysis revealed an enrichment of mutations in loci that occur in a gas-1
      centric region of the C. elegans interactome, and could be classified into a
      small number of functional-genomic categories. Characterization of a backcrossed
      four-mutation set isolated from one gas-1 MA line revealed this combination to be
      beneficial on both gas-1 mutant and wildtype genetic backgrounds. Our combined
      results suggest that selection favoring beneficial mutations can be powerful even
      under unfavorable population genetic conditions, and agree with fitness landscape
      theory predicting an inverse relationship between population fitness and the
      likelihood of adaptation.

PMID- 29069346
TI  - Outbreak of Invasive Infections From Subtype emm26.3 Group A Streptococcus Among
      Homeless Adults-Anchorage, Alaska, 2016-2017.
AB  - Background: In 2016, we detected an outbreak of group A Streptococcus (GAS)
      invasive infections among the estimated 1000 persons experiencing homelessness
      (PEH) in Anchorage, Alaska. We characterized the outbreak and implemented a mass
      antibiotic intervention at homeless service facilities. Methods: We identified
      cases through the Alaska GAS laboratory-based surveillance system. We conducted
      emm typing, antimicrobial susceptibility testing, and whole-genome sequencing on
      all invasive isolates and compared medical record data of patients infected with
      emm26.3 and other emm types. In February 2017, we offered PEH at 6 facilities in
      Anchorage a single dose of 1 g of azithromycin. We collected oropharyngeal and
      nonintact skin swabs on a subset of participants concurrent with the intervention
      and 4 weeks afterward. Results: From July 2016 through April 2017, we detected 42
      invasive emm26.3 cases in Anchorage, 35 of which were in PEH. The emm26.3
      isolates differed on average by only 2 single-nucleotide polymorphisms. Compared
      to other emm types, infection with emm26.3 was associated with cellulitis (odds
      ratio [OR], 2.5; P = .04) and necrotizing fasciitis (OR, 4.4; P = .02). We
      dispensed antibiotics to 391 PEH. Colonization with emm26.3 decreased from 4% of
      277 at baseline to 1% of 287 at follow-up (P = .05). Invasive GAS incidence
      decreased from 1.5 cases per 1000 PEH/week in the 6 weeks prior to the
      intervention to 0.2 cases per 1000 PEH/week in the 6 weeks after (P = .01).
      Conclusions: In an invasive GAS outbreak in PEH in Anchorage, mass antibiotic
      administration was temporally associated with reduced invasive disease cases and
      colonization prevalence.

PMID- 29069348
TI  - Photophase Duration Affects Immature Black Soldier Fly (Diptera: Stratiomyidae)
      Development.
AB  - This study tested the effect of photophase duration on black soldier fly,
      Hermetia illucens (L.; Diptera: Stratiomyidae), development. Successful larval
      eclosion, development time and adult emergence were measured for individuals
      exposed to 0 h, 8 h, and 12 h of light, at approximately 27 degrees C and 70%
      relative humidity. Accumulated degree hours (ADH) were calculated to correct for
      differences in temperature across treatments. Larvae successfully eclosed in all
      treatments, with larvae in 12 h light requiring 5.77% and 4.5% fewer ADH to
      eclose than larvae in 0 h and 8 h, respectively. Overall, larvae in 0 h required
      39.34% and 37.78% more ADH to complete their development from egg to adult than
      larvae in 8 h and 12 h, respectively. The effect of photophase duration on
      juvenile development was largest in the post-feeding stage, and smallest in the
      pupal stage. Specifically, post-feeding larvae in 0 h required 80.02% and 90.08%
      more ADH to pupate than larvae in 8 h and 12 h, respectively, but pupae in 8 h
      required 9.63% and 7.52% fewer ADH to eclose than pupae in 0 h and 12 h,
      respectively. Lastly, larval mortality was significantly higher in 0 h, with 72%
      survivorship, and 96% and 97% in 8 h and 12 h, respectively. However, 17.8% of
      mortality in the absence of light is hypothesized to be a result of predation by
      Arachnidae and Blattidae. These data could prove valuable for optimizing
      industrial processes for mass-production of this species for use as alternative
      protein in feed for livestock, poultry, and aquaculture.

PMID- 29069349
TI  - Legionella Becoming a Mutualist: Adaptive Processes Shaping the Genome of
      Symbiont in the Louse Polyplax serrata.
AB  - Legionellaceae are intracellular bacteria known as important human pathogens. In
      the environment, they are mainly found in biofilms associated with amoebas. In
      contrast to the gammaproteobacterial family Enterobacteriaceae, which established
      a broad spectrum of symbioses with many insect taxa, the only instance of
      legionella-like symbiont has been reported from lice of the genus Polyplax. Here,
      we sequenced the complete genome of this symbiont and compared its main
      characteristics to other Legionella species and insect symbionts. Based on
      rigorous multigene phylogenetic analyses, we confirm this bacterium as a member
      of the genus Legionella and propose the name Candidatus Legionella polyplacis,
      sp.n. We show that the genome of Ca. Legionella polyplacis underwent massive
      degeneration, including considerable size reduction (529.746 bp, 484 protein
      coding genes) and a severe decrease in GC content (23%). We identify several
      possible constraints underlying the evolution of this bacterium. On one hand, Ca.
      Legionella polyplacis and the louse symbionts Riesia and Puchtella experienced
      convergent evolution, perhaps due to adaptation to similar hosts. On the other
      hand, some metabolic differences are likely to reflect different phylogenetic
      positions of the symbionts and hence availability of particular metabolic
      function in the ancestor. This is exemplified by different arrangements of
      thiamine metabolism in Ca. Legionella polyplacis and Riesia. Finally, horizontal
      gene transfer is shown to play a significant role in the adaptive and
      diversification process. Particularly, we show that Ca. L. polyplacis
      horizontally acquired a complete biotin operon (bioADCHFB) that likely assisted
      this bacterium when becoming an obligate mutualist.

PMID- 29069350
TI  - A dose-response study of glutamate supplementation in isolated, perfused rat
      hearts undergoing ischaemia and cold cardioplegia.
AB  - OBJECTIVES: Several studies have reported superior post-cardioplegic recovery
      after glutamate supplementation. The optimum dose of glutamate supplementation is
      unknown. The purpose of this study was to find the optimal protective
      concentration of glutamate supplementation in a model of ischaemia/cardioplegia
      and reperfusion. METHODS: Isolated rat hearts (n = 77) were perfused with the
      Krebs-Henseleit buffer. After stabilization, the hearts were subjected to 25 min
      of normothermic ischaemia followed by a single 3-min infusion of cold (4-6 
      degrees C) St. Thomas' Hospital II cardioplegia and 87 min of cardioplegic
      ischaemic arrest and 60 min of reperfusion. Sodium-l-glutamate was added to the
      perfusate (control group had zero glutamate) in increasing concentrations (0.01,
      0.1, 1, 10, 20, 30 and 100 mM) and given throughout perfusion. Corresponding
      concentrations were added to the cardioplegic solution. A balloon in the left
      ventricle inserted via the left atrium measured left ventricular pressures
      isometrically. Left ventricular developed pressure was calculated. Myocardial
      exchange of glucose and lactate was measured prior to ischaemia and during
      reperfusion. Myocardial content of glycogen and glutamate was measured at the end
      of reperfusion. RESULTS: During reperfusion left ventricular developed pressure
      increased (P < 0.0001) in groups supplemented with 0.1, 1.0, 10, 20 and 30 mM
      glutamate, whereas left ventricular end-diastolic pressure was attenuated (P =
      0.008) when compared with the controls. No additional benefit on the continuous
      data left ventricular developed pressure and left ventricular end-diastolic
      pressure was observed with glutamate concentrations above 1 mM. Onset of LV
      pressure rise during the period of ischaemia was delayed by 100 mM of glutamate
      (P = 0.02). Myocardial content of glutamate was increased in a dose-related
      manner in Groups 10, 20, 30 and 100 compared with the control hearts (P <
      0.0001). Glycogen was increased in the hearts supplemented with 100 mM of
      glutamate (P = 0.02). CONCLUSIONS: Even low concentrations of l-glutamate
      improved postischaemic and post-cardioplegic heart function and 1 mM seems to be
      optimal.

PMID- 29069351
TI  - Impact of arch reobstruction and early hypertension on late hypertension after
      coarctation repair.
AB  - OBJECTIVES: Late hypertension after coarctation repair is associated with high
      mortality, but its risk factors remain unclear. This study aims to determine
      early and late postoperative risk factors for late hypertension after coarctation
      repair. METHODS: A cross-sectional study including transthoracic echocardiogram
      and 24-h blood pressure (BP) monitoring was performed in 144 patients aged >=10
      years with previous coarctation repair. Median age at repair was 39 days
      (interquartile range 0-3 years). Early postoperative hypertension was evaluated
      by calculating the mean of BP measurements taken on the same day before hospital
      discharge or the need for antihypertensives prior to discharge. Multivariable
      analyses were performed to adjust for gender, surgical age, and follow-up age.
      RESULTS: After a mean follow-up period of 22 +/- 7 years, 59% (84/142) of
      patients were hypertensive: 58% (82/142) on 24-h BP monitoring and 1% (2/142) on
      antihypertensives. Early postoperative hypertension was present in 58% (73/126):
      39% (49/126) on BP measurements and 19% (24/126) on antihypertensives. Early and
      late arch reobstruction (transthoracic echocardiogram peak gradient >=25 mmHg)
      was present in 37% (23/62) and 23% (33/144), respectively. On multivariable
      logistic analysis, early postoperative hypertension and maximum descending arch
      velocity on echocardiography were associated with late hypertension on 24-h BP
      monitoring (odds ratio 2.21, 95% confidence interval 1.05-4.66, P = 0.04; and
      odds ratio 2.28, 95% confidence interval 1.08-4.81, P = 0.03; respectively).
      CONCLUSIONS: There is a high prevalence of late hypertension after coarctation
      repair. Arch reobstruction may be a major determinant of late hypertension. Early
      postoperative hypertension may identify very early in life those at risk of
      developing late hypertension.

PMID- 29069352
TI  - The gorgonian coral Eunicella labiata hosts a distinct prokaryotic consortium
      amenable to cultivation.
AB  - Microbial communities inhabiting gorgonian corals are believed to benefit their
      hosts through nutrient provision and chemical defence; yet much remains to be
      learned about their phylogenetic uniqueness and cultivability. Here, we
      determined the prokaryotic community structure and distinctiveness in the
      gorgonian Eunicella labiata by Illumina sequencing of 16S rRNA genes from
      gorgonian and seawater metagenomic DNA. Furthermore, we used a 'plate-wash'
      methodology to compare the phylogenetic diversity of the 'total' gorgonian
      bacteriome and its 'cultivatable' fraction. With 1016 operational taxonomic units
      (OTUs), prokaryotic richness was higher in seawater than in E. labiata where 603
      OTUs were detected, 68 of which were host-specific. Oceanospirillales and
      Rhodobacterales predominated in the E. labiata communities. One Oceanospirillales
      OTU, classified as Endozoicomonas, was particularly dominant, and closest
      relatives comprised exclusively uncultured clones from other gorgonians. We
      cultivated a remarkable 62% of the bacterial symbionts inhabiting E. labiata:
      Ruegeria, Sphingorhabdus, Labrenzia, other unclassified Rhodobacteraceae, Vibrio
      and Shewanella ranked among the 10 most abundant genera in both the cultivation
      independent and dependent samples. In conclusion, the E. labiata microbiome is
      diverse, distinct from seawater and enriched in (gorgonian)-specific bacterial
      phylotypes. In contrast to current understanding, many dominant E. labiata
      symbionts can, indeed, be cultivated.

PMID- 29069353
TI  - Concurrent Lactic and Volatile Fatty Acid Analysis of Microbial Fermentation
      Samples by Gas Chromatography with Heat Pre-treatment.
AB  - Organic acid analysis of fermentation samples can be readily achieved by gas
      chromatography (GC), which detects volatile organic acids. However, lactic acid,
      a key fermentation acid is non-volatile and can hence not be quantified by
      regular GC analysis. However the addition of periodic acid to organic acid
      samples has been shown to enable lactic acid analysis by GC, as periodic acid
      oxidizes lactic acid to the volatile acetaldehyde. Direct GC injection of lactic
      acid standards and periodic acid generated inconsistent and irreproducible peaks,
      possibly due to incomplete lactic acid oxidation to acetaldehyde. The described
      method is developed to improve lactic acid analysis by GC by using a heat treated
      derivatization pre-treatment, such that it becomes independent of the retention
      time and temperature selection of the GC injector. Samples containing lactic acid
      were amended by periodic acid and heated in a sealed test tube at 100 degrees C
      for at least 45 min before injecting it to the GC. Reproducible and consistent
      peaks of acetaldehyde were obtained. Simultaneous determination of lactic acid,
      acetone, ethanol, butanol, volatile fatty acids could also be accomplished by
      applying this GC method, enabling precise and convenient organic acid analysis of
      biological samples such as anaerobic digestion and fermentation processes.

PMID- 29069355
TI  - Intention to treat (ITT) analysis as reported in orthodontic randomized
      controlled trials-evaluations of methodology and recommendations for the accurate
      use of ITT analysis and handling dropouts.
AB  - Objective: To systematically evaluate in five orthodontic journals how many
      randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to
      assess the methodological quality of the ITT analysis, and finally, to
      demonstrate in an academic way how outcomes can be affected when not implementing
      the ITT analysis. Material and methods: A search of the database, Medline, was
      performed via PubMed for publication type 'randomized controlled trial' published
      for each journal between 1 January 2013 and 30 April 2017. The five orthodontic
      journals assessed were the American Journal of Orthodontics and Dentofacial
      Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of
      Orthodontics, and Orthodontics and Craniofacial Research. Two independent
      reviewers assessed each RCT to determine whether the trial reported an ITT or not
      or if a per-protocol analysis was accomplished. Results: The initial search
      generated 137 possible trials. After applying the inclusion and exclusion
      criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%)
      either reported an ITT analysis in the text and/or supported the ITT by flow
      diagrams or tables. However, six RCTs applied and reported the ITT analysis
      correctly, while the majority performed a per-protocol analysis instead.
      Conclusions: Nearly all the trials that applied the ITT analysis incorrectly
      analysed the results using a per-protocol analysis, and thus, overestimating the
      results and/or having a reduced sample size which then could produce a diminished
      statistical power.

PMID- 29069354
TI  - The Diversification of Zika Virus: Are There Two Distinct Lineages?
AB  - Zika virus (ZIKV) has caused explosive epidemics in the Pacific and the Americas,
      posing a serious threat to public health. Conventional opinion advocates that
      ZIKV evolved into two distinct lineages, namely, African and Asian. Descendants
      of this latter lineage dispersed globally causing major epidemics. However, based
      on shared amino acid replacements and phylogenetic analyses, it was recently
      contentiously proposed that the Asian lineage was a direct descendant of the
      African lineage. To address this contentious issue, we reconstructed a
      phylogenetic tree of ZIKV using the method based on shared amino acid
      replacements and found that ZIKV evolved into two distinct lineages. This
      supports the conventional phylogenetic divergence pattern of ZIKV. Evidence of
      recombination and sequencing errors was identified among the large collection of
      ZIKV. As such problematic sequences could confound the phylogenetic analyses,
      they were removed. Bayesian phylogenetic analyses using the improved sequence
      data enabled estimates for the divergence time in the past of the African and
      Asian lineages of ~180 years ago. Moreover, we found that the Asian lineage
      viruses did not evolve at an elevated rate. Our findings provide additional
      support for the conventional opinion that the Asian lineage of ZIKV diverged from
      the African lineage.

PMID- 29069356
TI  - Glucocorticoid Receptor Signaling Impairs Protein Turnover Regulation in Hypoxia
      Induced Muscle Atrophy in Male Mice.
AB  - Hypoxemia may contribute to muscle wasting in conditions such as chronic
      obstructive pulmonary disease. Muscle wasting develops when muscle proteolysis
      exceeds protein synthesis. Hypoxia induces skeletal muscle atrophy in mice, which
      can in part be attributed to reduced food intake. We hypothesized that hypoxia
      elevates circulating corticosterone concentrations by reduced food intake and
      enhances glucocorticoid receptor (GR) signaling in muscle, which causes elevated
      protein degradation signaling and dysregulates protein synthesis signaling during
      hypoxia-induced muscle atrophy. Muscle-specific GR knockout and control mice were
      subjected to normoxia, normobaric hypoxia (8% oxygen), or pair-feeding to the
      hypoxia group for 4 days. Plasma corticosterone and muscle GR signaling increased
      after hypoxia and pair-feeding. GR deficiency prevented muscle atrophy by pair
      feeding but not by hypoxia. GR deficiency differentially affected activation of
      ubiquitin 26S-proteasome and autophagy proteolytic systems by pair-feeding and
      hypoxia. Reduced food intake suppressed mammalian target of rapamycin complex 1
      (mTORC1) activity under normoxic but not hypoxic conditions, and this retained
      mTORC1 activity was mediated by GR. We conclude that GR signaling is required for
      muscle atrophy and increased expression of proteolysis-associated genes induced
      by decreased food intake under normoxic conditions. Under hypoxic conditions,
      muscle atrophy and elevated gene expression of the ubiquitin proteasomal system
      associated E3 ligases Murf1 and Atrogin-1 are mostly independent of GR signaling.
      Furthermore, impaired inhibition of mTORC1 activity is GR-dependent in hypoxia
      induced muscle atrophy.

PMID- 29069357
TI  - Annuloplasty band implantation in adults with partial atrioventricular septal
      defect: a propensity-matched study.
AB  - OBJECTIVES: The incidence of recurrent left atrioventricular valve (LAVV)
      regurgitation is generally high after repair of partial atrioventricular septal
      defect (AVSD). This study aimed to evaluate the effect of implanting an
      additional annuloplasty band into the LAVV during partial AVSD repair and to
      assess the late outcomes of recurrent LAVV regurgitation. METHODS: This study
      enrolled 133 patients who underwent repair of partial AVSD at our institution
      from January 2005 to December 2015. All patients underwent repair of the ostium
      primum atrial septal defect and closure of the LAVV cleft; 37 patients underwent
      additional annuloplasty band implantation. To minimize differences in
      preoperative data, propensity score matching was used to identify 33 well-matched
      patient pairs. RESULTS: Cardiopulmonary bypass time and aorta cross-clamp time
      were significantly longer in the band implantation group (P < 0.05). The 2 groups
      had similar durations of intensive care and hospital stay (P > 0.05). There was 1
      in-hospital death in the band implantation group. During follow-up, conduction
      block occurred in 6 patients in each group. After follow-up of more than 10
      years, freedom from late recurrent LAVV regurgitation was 91% in the band
      implantation group and 57% in the isolated cleft closure group (P < 0.05). In
      patients with preoperative severe regurgitation and moderate/mild regurgitation,
      the rates of freedom from recurrent LAVV regurgitation were 85% and 37%,
      respectively (P < 0.05). CONCLUSIONS: In patients with moderate/severe LAVV
      regurgitation or severe annular dilation, additional band implantation
      significantly reduces the incidence of recurrent regurgitation and improves long
      term outcomes.

PMID- 29069358
TI  - Atrial function is altered in lone paroxysmal atrial fibrillation in male
      endurance veteran athletes.
AB  - Aims: Intensive endurance sport practice is associated with an increased risk of
      atrial fibrillation (AF) in male veteran athletes. Paroxysmal AF (PAF) is the
      very beginning step of this disease. The description of atrial remodelling
      occurring at this early stage might enable to depict predictive factors of AF in
      veteran athletes in order to give them personalized recommendation according to
      their sport practice. Methods and results: Twenty-seven male endurance veteran
      athletes with documented PAF were retrospectively enrolled and compared with 30
      control endurance athletes without documented AF, with similar training level,
      age, and cardiovascular risk factors. All subjects underwent a resting
      electrocardiogram (ECG) to assess the electric remodelling of P-waves as well as
      an echocardiography, to evaluate the left and right atrial (LA, RA) anatomical
      and functional (assessed by 2D strain) remodelling. No difference was noted
      between groups for the ECG P-wave parameters. Atrial function was decreased in
      the PAF group, particularly the peak atrial longitudinal strain (L-E-Max) of LA
      (29.3 +/- 7.9% vs. 49.1 +/- 7.8% respectively in the PAF group and in controls, P
      < 0.0001) and RA (36.5 +/- 7.0% vs. 50.6 +/- 10.2%, P < 0.0001). LA and RA
      volumes were also larger in the PAF group. Receiver operating characteristic
      analysis demonstrated that L-E-Max of LA [area under curve (AUC): 0.957 +/-
      0.023] and RA (AUC: 0.901 +/- 0.042) had the best ability to identify the
      athletes with PAF, far better than the anatomical parameters (AUC < 0.75 in all).
      Conclusion: Atrial function analysed by strain in echocardiography is strongly
      associated with PAF and might enable to identify male endurance veteran athletes
      at risk to develop AF.

PMID- 29069359
TI  - A biomarker-based risk score to predict death in patients with atrial
      fibrillation: the ABC (age, biomarkers, clinical history) death risk score.
AB  - Aims: In atrial fibrillation (AF), mortality remains high despite effective
      anticoagulation. A model predicting the risk of death in these patients is
      currently not available. We developed and validated a risk score for death in
      anticoagulated patients with AF including both clinical information and
      biomarkers. Methods and results: The new risk score was developed and internally
      validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a
      median of 1.9 years. External validation was performed in 8548 patients with AF
      randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were
      obtained at study entry. Variables significantly contributing to the prediction
      of all-cause mortality were assessed by Cox-regression. Each variable obtained a
      weight proportional to the model coefficients. There were 1047 all-cause deaths
      in the derivation and 594 in the validation cohort. The most important predictors
      of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth
      differentiation factor-15, age, and heart failure, and these were included in the
      ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well
      calibrated and yielded higher c-indices than a model based on all clinical
      variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs.
      0.67). The reduction in mortality with apixaban was most pronounced in patients
      with a high ABC-death score. Conclusion: A new biomarker-based score for
      predicting risk of death in anticoagulated AF patients was developed, internally
      and externally validated, and well-calibrated in two large cohorts. The ABC-death
      risk score performed well and may contribute to overall risk assessment in AF.
      ClinicalTrials.gov identifier: NCT00412984 and NCT00262600.

PMID- 29069361
TI  - Climate Change Impacts on the Potential Distribution and Abundance of the Brown
      Marmorated Stink Bug (Hemiptera: Pentatomidae) With Special Reference to North
      America and Europe.
AB  - The invasive brown marmorated stink bug, Halyomorpha halys (Stal; Hemiptera:
      Pentatomidae), has recently emerged as a harmful pest of horticultural crops in
      North America and Europe. Native to East Asia, this highly polyphagous insect is
      spreading rapidly worldwide. Climate change will add further complications to
      managing this species in terms of both geographic distribution and population
      growth. This study used CLIMEX to compare potential H. halys distribution under
      recent and future climate models using one emission scenario (A2) with two
      different global circulation models, CSIRO Mk3.0 and MIROC-H. Simulated changes
      in seasonal phenology and voltinism were examined. Under the possible future
      climate scenarios, suitable range in Europe expands northward. In North America,
      the suitable H. halys range shifts northward into Canada and contracts from its
      southern temperature range limits in the United States due to increased heat
      stress. Prolonged periods of warm temperatures resulted in longer H. halys
      growing seasons. However, future climate scenarios indicated that rising summer
      temperatures decrease H. halys growth potential compared to recent climatic
      conditions, which in turn, may reduce mid-summer crop damage. Climate change may
      increase the number of H. halys generations produced annually, thereby enabling
      the invasive insect to become multivoltine in the northern latitudes of North
      America and Europe where it is currently reported to be univoltine. These results
      indicate prime horticultural production areas in Europe, the northeastern United
      States, and southeastern Canada are at greatest risk from H. halys under both
      current and possible future climates.

PMID- 29069360
TI  - Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology.
AB  - Primary aldosteronism (PA) is a common form of endocrine hypertension that is
      characterized by the excessive production of aldosterone relative to suppressed
      plasma renin levels. PA is usually caused by either a unilateral aldosterone
      producing adenoma or bilateral adrenal hyperplasia. Somatic mutations have been
      identified in several genes that encode ion pumps and channels that may explain
      the aldosterone excess in over half of aldosterone-producing adenomas, whereas
      the pathophysiology of bilateral adrenal hyperplasia is largely unknown. A number
      of mouse models of hyperaldosteronism have been described that recreate some
      features of the human disorder, although none replicate the genetic basis of
      human PA. Animal models that reproduce the genotype-phenotype associations of
      human PA are required to establish the functional mechanisms that underlie the
      endocrine autonomy and deregulated cell growth of the affected adrenal and for
      preclinical studies of novel therapeutics. Herein, we discuss the differences in
      adrenal physiology across species and describe the genetically modified mouse
      models of PA that have been developed to date.

PMID- 29069362
TI  - Immediate Antiretroviral Therapy Decreases Mortality Among Patients With High CD4
      Counts in China: A Nationwide, Retrospective Cohort Study.
AB  - Background: Clinical trials have demonstrated that immediate initiation of
      antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality. We
      tested the hypothesis that initiating ART <=30 days after human immunodeficiency
      virus (HIV) diagnosis would be associated with reduced mortality among people
      living with HIV (PLWH) with CD4 counts >500 cells/MUL. Methods: PLWH enrolled in
      the Chinese National HIV Information System between January 2012 and June 2014
      with CD4 counts >500 cells/MUL were followed for 12 months. Cox proportional
      hazards model was used to determine hazard ratios (HRs) for PLWH who initiated
      ART after HIV diagnosis. ART initiation was treated as a time-dependent variable.
      Results: We enrolled 34581 PLWH with CD4 >500 cells/MUL; 1838 (5.3%) initiated
      ART <=30 days after diagnosis (immediate ART group), and 19 deaths were observed
      with a mortality rate of 1.04 per 100 person-years (PY). Fifty-eight deaths were
      documented among the 5640 PLWH in the delayed ART group with a mortality rate of
      2.25 per 100 PY. There were 713 deaths among the 27103 PLWH in the no ART group
      with a mortality rate of 2.39 per 100 PY. After controlling for potential
      confounding factors, ART initiation at <=30 days (adjusted HR, 0.37 [95%
      confidence interval, .23-.58]) was a statistically significant protective factor.
      Conclusions: We found that immediate ART is associated with a 63% reduction in
      overall mortality among PLWH with CD4 counts >500 cells/MUL in China, supporting
      the recommendation to initiate ART immediately following HIV diagnosis.

PMID- 29069364
TI  - Pulmonary vein stenosis or occlusion after catheter ablation of atrial
      fibrillation: long-term comparison of drug-eluting versus large bare metal
      stents.
AB  - Aims: Pulmonary vein stenosis or occlusion (PVS/O) following catheter ablation of
      atrial fibrillation is a rare but potentially severe complication. Treatment
      options include angioplasty with or without stent implantation, but data on
      outcome and optimal treatment strategy are limited. We report long-term results
      after catheter-based treatment of patients with symptomatic PVS/O. Methods and
      results: Retrospective analysis was performed in patients undergoing pulmonary
      vein (PV) angiography for suspected PVS/O. All patients with PVS/O were treated
      with balloon angioplasty and implantation of a coronary drug-eluting stent (DES)
      or a peripheral large-diameter bare metal stent (LD-BMS). A total of 25 high
      degree PVS/Os in 19 patients were treated. Nine PVs were treated with angioplasty
      and DES implantation and 16 with angioplasty and LD-BMS implantation. The ostial
      PV diameter was not different in the DES and LD-BMS groups (10.2 +/- 2.5 mm vs.
      11.1 +/- 1.9 mm, P = 0.34), but the PV/stent diameter ratio was significantly
      lower in the former (0.43 +/- 0.13 vs. 0.82 +/- 0.13, P < 0.0001). Angiographic
      stent restenosis was observed at a median of 539 (interquartile range 99-774)
      days in 9 of 23 (39%) treated PVs. The restenosis rate in the LD-BMS group was
      only one-third of that in the DES group [3/14 (21%) vs. 6/9 (67%), respectively;
      P = 0.08]. Conclusion: The use of LD-BMS for the treatment of PVS/O was
      associated with an acceptable long-term outcome. Coronary DES implantation
      resulted in a high rate of restenosis and should therefore not be performed.
      Larger trials are needed to confirm our findings.

PMID- 29069363
TI  - Lateralized Feeding Behavior is Associated with Asymmetrical Neuroanatomy and
      Lateralized Gene Expressions in the Brain in Scale-Eating Cichlid Fish.
AB  - Lateralized behavior ("handedness") is unusual, but consistently found across
      diverse animal lineages, including humans. It is thought to reflect brain
      anatomical and/or functional asymmetries, but its neuro-molecular mechanisms
      remain largely unknown. Lake Tanganyika scale-eating cichlid fish, Perissodus
      microlepis show pronounced asymmetry in their jaw morphology as well as
      handedness in feeding behavior-biting scales preferentially only from one or the
      other side of their victims. This makes them an ideal model in which to
      investigate potential laterality in neuroanatomy and transcription in the brain
      in relation to behavioral handedness. After determining behavioral handedness in
      P. microlepis (preferred attack side), we estimated the volume of the hemispheres
      of brain regions and captured their gene expression profiles. Our analyses
      revealed that the degree of behavioral handedness is mirrored at the level of
      neuroanatomical asymmetry, particularly in the tectum opticum. Transcriptome
      analyses showed that different brain regions (tectum opticum, telencephalon,
      hypothalamus, and cerebellum) display distinct expression patterns, potentially
      reflecting their developmental interrelationships. For numerous genes in each
      brain region, their extent of expression differences between hemispheres was
      found to be correlated with the degree of behavioral lateralization.
      Interestingly, the tectum opticum and telencephalon showed divergent biases on
      the direction of up- or down-regulation of the laterality candidate genes (e.g.,
      grm2) in the hemispheres, highlighting the connection of handedness with gene
      expression profiles and the different roles of these brain regions. Hence,
      handedness in predation behavior may be caused by asymmetric size of brain
      hemispheres and also by lateralized gene expressions in the brain.

PMID- 29069366
TI  - Uncommon carbapenemase-encoding plasmids in the clinically emergent Acinetobacter
      pittii.
AB  - Objectives: Two carbapenemase-carrying plasmids, pLS488 (blaOXA-23) and pLS535
      (blaOXA-58) from Acinetobacter pittii clinical isolates, were characterized in
      this study, including their ability to be transferred to Acinetobacter baumannii.
      Methods: The clinical isolates were obtained from drainage fluid of a patient
      with biliary tract cancer and from an exudate of a patient with a hip infection
      (Portuguese University Hospital, 2012). Isolate characterization included
      antimicrobial susceptibility tests, carbapenemase production by Blue-Carba,
      carbapenem-hydrolysing class D beta-lactamase (CHDL) gene search by PCR
      sequencing, ApaI-PFGE, CHDL genetic location and plasmid size by hybridization
      and WGS. Plasmid transfer was performed by conjugation or electroporation.
      Results: pLS488 constitutes the first conjugative plasmid reported to carry a
      carbapenem resistance gene in A. pittii and is part of a potential new
      incompatibility group that might also account for the dissemination of OXA-23 in
      A. baumannii. pLS535 belongs to the Acinetobacter GR7 incompatibility group and
      presents a new scaffold for OXA-58. This plasmid lacked the machinery for
      conjugation, but was transferable by electroporation to A. baumannii. Both
      isolates, which displayed the same PFGE pattern, represent the first report of
      CHDL-carrying A. pittii in Portuguese hospitals. Conclusions: Altogether, these
      results emphasize the importance of A. pittii, or particular A. pittii clones, as
      a source of resistance genes, facilitating their dissemination among different
      bacterial species.

PMID- 29069367
TI  - The effect of bacterial chemotaxis on host infection and pathogenicity.
AB  - Chemotaxis enables microorganisms to move according to chemical gradients.
      Although this process requires substantial cellular energy, it also affords key
      physiological benefits, including enhanced access to growth substrates. Another
      important implication of chemotaxis is that it also plays an important role in
      infection and disease, as chemotaxis signalling pathways are broadly distributed
      across a variety of pathogenic bacteria. Furthermore, current research indicates
      that chemotaxis is essential for the initial stages of infection in different
      human, animal and plant pathogens. This review focuses on recent findings that
      have identified specific bacterial chemoreceptors and corresponding
      chemoeffectors associated with pathogenicity. Pathogenicity-related
      chemoeffectors are either host and niche-specific signals or intermediates of the
      host general metabolism. Plant pathogens were found to contain an elevated number
      of chemotaxis signalling genes and functional studies demonstrate that these
      genes are critical for their ability to enter the host. The expanding body of
      knowledge of the mechanisms underlying chemotaxis in pathogens provides a
      foundation for the development of new therapeutic strategies capable of blocking
      infection and preventing disease by interfering with chemotactic signalling
      pathways.

PMID- 29069365
TI  - Monocyte and haematopoietic progenitor reprogramming as common mechanism
      underlying chronic inflammatory and cardiovascular diseases.
AB  - A large number of cardiovascular events are not prevented by current therapeutic
      regimens. In search for additional, innovative strategies, immune cells have been
      recognized as key players contributing to atherosclerotic plaque progression and
      destabilization. Particularly the role of innate immune cells is of major
      interest, following the recent paradigm shift that innate immunity, long
      considered to be incapable of learning, does exhibit immunological memory
      mediated via epigenetic reprogramming. Compelling evidence shows that
      atherosclerotic risk factors promote immune cell migration by pre-activation of
      circulating innate immune cells. Innate immune cell activation via metabolic and
      epigenetic reprogramming perpetuates a systemic low-grade inflammatory state in
      cardiovascular disease (CVD) that is also common in other chronic inflammatory
      disorders. This opens a new therapeutic area in which metabolic or epigenetic
      modulation of innate immune cells may result in decreased systemic chronic
      inflammation, alleviating CVD, and its co-morbidities.

PMID- 29069368
TI  - Immune Responses to Twice-Annual Influenza Vaccination in Older Adults in Hong
      Kong.
AB  - Background: Many health authorities recommend influenza vaccination of older
      adults to reduce disease burden. We hypothesized that in tropical and subtropical
      areas with more prolonged influenza seasons, twice-annual influenza vaccination
      might provide older adults with improved immunity against influenza. Methods: In
      2014-2015, Hong Kong experienced a substantial A(H3N2) winter epidemic with a
      mismatched vaccine. Local authorities procured and administered to older adults
      the 2015 southern hemisphere influenza vaccine, which included an updated and
      matching A/Switzerland/9715293/2013(H3N2) strain. We compared immune parameters
      in pre- and postvaccination sera from older adults >=75 years of age who received
      1 vs 2 influenza vaccines per year. Results: We enrolled 978 older adults with
      470 vaccinations for summer 2015 and 827 vaccinations for winter 2015-2016.
      Recipients of southern hemisphere vaccination had higher geometric mean titers
      (GMTs) by the hemagglutination inhibition assay against all 3 vaccine strains.
      When receiving influenza vaccination for the subsequent winter, the southern
      hemisphere vaccine recipients had higher prevaccination GMTs but lower
      postvaccination GMTs, compared to those who had not received the southern
      hemisphere vaccine. Furthermore, cellular immunity was impacted by biannual
      vaccination, with reduced influenza-specific CD4 T-cell responses in the second
      season of vaccination. Conclusions: We observed some reductions in immune
      responses in the twice-annual vaccination group compared with the once-annual
      vaccination group, in the context of unchanging vaccine strains, while protection
      was likely to have been improved during the summer and autumn for the twice
      annual vaccination group due to the continued circulation of the
      A/Switzerland/9715293/2013(H3N2) virus.

PMID- 29069369
TI  - High-resolution three-dimensional late gadolinium-enhanced cardiac magnetic
      resonance imaging to identify the underlying substrate of ventricular arrhythmia.
AB  - Aims: Cardiac magnetic resonance (CMR) is recommended as a second-line method to
      diagnose ventricular arrhythmia (VA) substrate. We assessed the diagnostic yield
      of CMR including high-resolution late gadolinium-enhanced (LGE) imaging. Methods
      and results: Consecutive patients with sustained ventricular tachycardia (VT),
      non-sustained VT (NSVT), or ventricular fibrillation/aborted sudden death
      (VF/SCD) underwent a non-CMR diagnostic workup according to current guidelines,
      and CMR including LGE imaging with both a conventional breath-held and a free
      breathing method enabling higher spatial resolution (HR-LGE). The diagnostic
      yield of CMR was compared with the non-CMR workup, including the incremental
      value of HR-LGE. A total of 157 patients were enrolled [age 54 +/- 17 years; 75%
      males; 88 (56%) sustained VT, 52 (33%) NSVT, 17 (11%) VF/SCD]. Of these, 112
      (71%) patients had no history of structural heart disease (SHD). All patients
      underwent electrocardiography and echocardiography, 72% coronary angiography, and
      51% exercise testing. Pre-CMR diagnoses were 84 (54%) no SHD, 39 (25%) ischaemic
      cardiomyopathy (ICM), 11 (7%) non-ischaemic cardiomyopathy (NICM), 3 (2%)
      arrhythmogenic right ventricular cardiomyopathy (ARVC), 2 (1%) hypertrophic
      cardiomyopathy (HCM), and 18 (11%) other. CMR modified these diagnoses in 48
      patients (31% of all and 43% of those with no SHD history). New diagnoses were 9
      ICM, 28 NICM, 8 ARVC, 1 HCM, and 2 other. CMR modified therapy in 19 (12%)
      patients. In patients with no SHD after non-CMR tests, SHD was found in 32 of 84
      (38%) patients. Eighteen of these patients showed positive HR-LGE and negative
      conventional LGE. Thus, HR-LGE significantly increased the CMR detection of SHD
      (17-38%, P < 0.001). Conclusion: CMR including HR-LGE imaging has high diagnostic
      value in patients with VAs. This has major prognostic and therapeutic
      implications, particularly in patients with negative pre-CMR workup.

PMID- 29069370
TI  - Ten-year results of intense dose-dense chemotherapy show superior survival
      compared with a conventional schedule in high-risk primary breast cancer: final
      results of AGO phase III iddEPC trial.
AB  - Background: Primary breast cancer (BC) patients with extensive axillary lymph
      node involvement have a limited prognosis. The Arbeitsgemeinschaft fuer
      Gynaekologische Onkologie (AGO) trial compared intense dose-dense (idd) adjuvant
      chemotherapy with conventionally scheduled chemotherapy in high-risk BC patients.
      Here we report the final, 10-year follow-up analysis. Patients and methods:
      Enrolment took place between December 1998 and April 2003. A total of 1284
      patients with 4 or more involved axillary lymph nodes were randomly assigned to
      receive 3 courses each of idd sequential epirubicin, paclitaxel and
      cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by
      paclitaxel (EC -> P) q3w. Event-free survival (EFS) was the primary end point.
      Results: A total of 658 patients were assigned to receive iddEPC and 626 patients
      were assigned to receive EC -> P. The median duration of follow-up was 122
      months. EFS was 47% (95% CI 43% to 52%) in the standard group and 56% (95% CI 52%
      to 60%) in the iddEPC group [hazard ratio (HR) 0.74, 95% CI 0.63-0.87; log-rank P
      = 0.00014, one-sided]. This benefit was independent of menopausal, hormone
      receptor or HER2 status. Ten-year overall survival (OS) was 59% (95% CI 55% to
      63%) for patients in the standard group and 69% (95% CI 65% to 73%) for patients
      in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P = 0.0007, two
      sided). Nine versus two cases of secondary myeloid leukemia/myelodysplastic
      syndrome were observed in the iddEPC and the EC -> P arm, respectively.
      Conclusion: The previously reported OS benefit of iddEPC in comparison to
      conventionally dosed EC -> P has been further increased and achieved an absolute
      difference of 10% after 10 years of follow-up.

PMID- 29069371
TI  - Ventromedial Frontal Lobe Damage Alters how Specific Attributes are Weighed in
      Subjective Valuation.
AB  - The concept of subjective value is central to current neurobiological views of
      economic decision-making. Much of this work has focused on signals in the
      ventromedial frontal lobe (VMF) that correlate with the subjective value of a
      variety of stimuli (e.g., food, monetary gambles), and are thought to support
      decision-making. However, the neural processes involved in assessing and
      integrating value information from the attributes of such complex options remain
      to be defined. Here, we tested the necessary role of VMF in weighting attributes
      of naturalistic stimuli during value judgments. We asked how distinct attributes
      of visual artworks influenced the subjective value ratings of subjects with VMF
      damage, compared to healthy participants and a frontal lobe damaged control
      group. Subjects with VMF damage were less influenced by the energy (emotion,
      complexity) and color radiance (warmth, saturation) of the artwork, while they
      were similar to control groups in considering saliency, balance and concreteness.
      These dissociations argue that VMF is critical for allowing certain affective
      content to influence subjective value, while sparing the influence of perceptual
      or representational information. These distinctions are important for better
      defining the often-underspecified concept of subjective value and developing more
      detailed models of the brain mechanisms underlying decision behavior.

PMID- 29069372
TI  - Breakthrough Clostridium difficile Infection in Cirrhotic Patients Receiving
      Rifaximin.
AB  - Background: Patients with cirrhosis are at high risk of Clostridium difficile
      infection (CDI). Rifaximin is commonly used in cirrhotic patients as prophylaxis
      for hepatic encephalopathy (HE). Several studies have demonstrated the efficacy
      of rifaximin in the treatment of CDI; however, resistance to rifaximin has also
      been reported. Few studies have assessed the risk of developing CDI in cirrhotic
      patients receiving rifaximin. Our objective was to assess the incidence and
      characteristics of CDI in patients with cirrhosis, especially in those who
      received rifaximin. Methods: We assessed the incidence and clinical
      characteristics of CDI in cirrhotic patients over a 6-year period in our
      hospital. Medical charts were retrospectively reviewed. Ribotyping and
      antimicrobial susceptibility testing of all strains against rifaximin were
      performed. Results: A total of 388 cirrhotic patients were included, of whom 127
      patients had at least 1 episode of diarrhea in which a sample was sent to the
      laboratory. CDI was detected in 46 patients. Fourteen patients (30.4%) were
      receiving rifaximin as prophylaxis for HE. The main ribotypes detected were 001
      (30.4%), followed by 014 (19.6%). Resistance to rifaximin was 34.1% overall, and
      84.6% in patients who had received rifaximin. Multivariate analysis showed that
      rifamycin therapy and ribotype 001 were significant risk factors for having a
      rifaximin-resistant C. difficile strain. Conclusions: A high percentage of CDI
      cases were detected in cirrhotic patients receiving rifaximin, mostly owing to
      selection of rifaximin-resistant C. difficile strains. Clinicians should be aware
      of the risk of CDI in cirrhotic patients, even in those receiving rifaximin.

PMID- 29069373
TI  - Detection of Influenza C Viruses Among Outpatients and Patients Hospitalized for
      Severe Acute Respiratory Infection, Minnesota, 2013-2016.
AB  - Background: Existing literature suggests that influenza C typically causes mild
      respiratory tract disease. However, clinical and epidemiological data are
      limited. Methods: Four outpatient clinics and 3 hospitals submitted clinical data
      and respiratory specimens through a surveillance network for acute respiratory
      infection (ARI) from May 2013 through December 2016. Specimens were tested using
      multitarget nucleic acid amplification for 19-22 respiratory pathogens, including
      influenza C. Results: Influenza C virus was detected among 59 of 10 202 (0.58%)
      hospitalized severe ARI cases and 11 of 2282 (0.48%) outpatients. Most detections
      occurred from December to March, 73% during the 2014-2015 season. Influenza C
      detections occurred among patients of all ages, with rates being similar between
      inpatients and outpatients. The highest rate of detection occurred among children
      aged 6-24 months (1.2%). Among hospitalized cases, 7 required intensive care.
      Medical comorbidities were reported in 58% of hospitalized cases and all who
      required intensive care. At least 1 other respiratory pathogen was detected in 40
      (66%) cases, most commonly rhinovirus/enterovirus (25%) and respiratory syncytial
      virus (20%). The hemagglutinin-esterase-fusion gene was sequenced in 37
      specimens, and both C/Kanagawa and C/Sao Paulo lineages were detected in
      inpatients and outpatients. Conclusions: We found seasonal circulation of
      influenza C with year-to-year variability. Detection was most frequent among
      young children but occurred in all ages. Some cases that were positive for
      influenza C, particularly those with comorbid conditions, had severe disease,
      suggesting a need for further study of the role of influenza C virus in the
      pathogenesis of respiratory disease.

PMID- 29069374
TI  - Cellular shear stiffness reflects progression of arsenic-induced transformation
      during G1.
AB  - Cancer cells consistently exhibit decreased stiffness; however, the onset and
      progression of this change have not been characterized. To study the development
      of cell stiffness changes, we evaluated the shear stiffness of populations of
      cells during transformation to a carcinogenic state. Bronchial epithelial cells
      were exposed to sodium arsenite to initiate early stages of transformation.
      Exposed cells were cultured in soft agar to further transformation and select for
      clonal populations exhibiting anchorage-independent growth. Shear stiffness of
      various cell populations in G1 was assessed using a novel non-invasive assay that
      applies shear stress with fluid flow and evaluates nanoscale deformation using
      quantitative phase imaging (QPI). Arsenic-treated cells exhibited reduced
      stiffness relative to control cells, while arsenic clonal lines, selected by
      growth in soft agar, were found to have reduced stiffness relative to control
      clonal lines, which were cultured in soft agar but did not receive arsenic
      treatment. The relative standard deviation (RSD) of the stiffness of Arsenic
      clones was reduced compared with control clones, as well as to the arsenic
      exposed cell population. Cell stiffness at the population level exhibits
      potential to be a novel and sensitive framework for identifying the development
      of cancerous cells.

PMID- 29069375
TI  - A Lymph Node Ratio-Based Staging Model Is Superior to the Current Staging System
      for Pancreatic Neuroendocrine Tumors.
AB  - Context: The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing.
      Current staging systems include nodal positivity, but the association of lymph
      node status and worse survival is controversial. Objective: The study aim was to
      determine the prognostic significance of lymph node ratio (LNR) and compare it
      with nodal positivity for PNET. Design, Setting, Participants, and Intervention:
      A retrospective analysis of the Surveillance, Epidemiology, and End Results
      database between 2004 and 2011 was performed in patients who underwent a
      pancreatectomy with lymphadenectomy. The primary outcome was disease-specific
      survival (DSS). Results: Of the 896 patients analyzed, T stage, N stage, distant
      metastasis, grade, extent of resection, sex, and age >=57 years were
      significantly associated with worse DSS on univariate analysis. On multivariate
      analysis, age >=57 [hazard ratio (HR) 1.75, 95% confidence interval (CI), 1.12 to
      2.74, P = 0.015], male sex (HR 1.58; 95% CI, 1.01 to 2.48; P = 0.046), grade
      (poorly differentiated/undifferentiated: HR 7.59; 95% CI, 4.71 to 12.23; P <
      0.001), distant metastases (HR 2.45; 95% CI, 1.58 to 3.79; P < 0.001), and
      partial pancreatectomy (HR 2.55; 95% CI, 1.2 to 5.4; P = 0.015) were associated
      with worse DSS. Comparison between staging models constructed based on LNR
      cutoffs and the American Joint Committee on Cancer (AJCC) eighth edition staging
      system revealed that a model based on LNR >=0.5 was superior. Conclusions: LNR
      >=0.5 is independently associated with worse DSS. A staging system with LNR >=0.5
      was superior to the current AJCC eighth edition staging system.

PMID- 29069376
TI  - Contextual levers for team-based primary care: lessons from reform interventions
      in five jurisdictions in three countries.
AB  - Background: Most Western nations have sought primary care (PC) reform due to the
      rising costs of health care and the need to manage long-term health conditions. A
      common reform-the introduction of inter-professional teams into traditional PC
      settings-has been difficult to implement despite financial investment and
      enthusiasm. Objective: To synthesize findings across five jurisdictions in three
      countries to identify common contextual factors influencing the successful
      implementation of teamwork within PC practices. Methods: An international
      consortium of researchers met via teleconference and regular face-to-face
      meetings using a Collaborative Reflexive Deliberative Approach to re-analyse and
      synthesize their published and unpublished data and their own work experience.
      Studies were evaluated through reflection and facilitated discussion to identify
      factors associated with successful teamwork implementation. Matrices were used to
      summarize interpretations from the studies. Results: Seven common levers
      influence a jurisdiction's ability to implement PC teams. Team-based PC was
      promoted when funding extended beyond fee-for-service, where care delivery did
      not require direct physician involvement and where governance was inclusive of
      non-physician disciplines. Other external drivers included: the health
      professional organizations' attitude towards team-oriented PC, the degree of
      external accountability required of practices, and the extent of their links with
      the community and medical neighbourhood. Programs involving outreach
      facilitation, leadership training and financial support for team activities had
      some effect. Conclusion: The combination of physician dominance and physician
      aligned fee-for-service payment structures provide a profound barrier to
      implement team-oriented PC. Policy makers should carefully consider the influence
      of these and our other identified drivers when implementing team-oriented PC.

PMID- 29069377
TI  - Effect of statins and non-statin LDL-lowering medications on cardiovascular
      outcomes in secondary prevention: a meta-analysis of randomized trials.
AB  - Aims: Current evidence on dyslipidaemia management has expanded to novel
      treatments and very low achieved levels of low-density lipoprotein cholesterol
      (LDL-C). We sought to compare the clinical impact of more-intensive vs. less
      intensive LDL-C lowering by means of statins and currently recommended non-statin
      medications in secondary prevention. Methods and results: We searched Medline,
      EMBASE, and Cochrane databases for randomized controlled trials of statins,
      ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or
      bile acid sequestrants with >500 patients followed for >=1 year. We employed
      random-effects models using risk ratios (RRs) with 95% confidence intervals (CIs)
      to compare outcomes. We included 19 trials (15 of statins, 3 of PCSK9 inhibitors,
      and 1 of ezetimibe) with 152 507 patients randomly assigned to more-intensive (n
      = 76 678) or less-intensive treatment (n = 75 829). More-intensive treatment was
      associated with 19% relative risk reduction for the primary outcome, major
      vascular events (MVEs; RR 0.81, 95% CI 0.77-0.86). Risk reduction was greater
      across higher baseline levels and greater achieved reductions of LDL-C. The
      clinical benefit was significant across varying types of more-intensive treatment
      and was consistent for statins (RR 0.81, 95% CI 0.76-0.86) and non-statin agents
      (PCSK9 inhibitors and ezetimibe; RR 0.85, 95% CI 0.77-0.94) as active (more
      intensive) intervention (P-interaction = 0.38). Each 1.0 mmol/L reduction in LDL
      C was associated with 19% relative decrease in MVE. Death, cardiovascular death,
      myocardial infarction, stroke, and coronary revascularization also favoured more
      intensive treatment. Conclusion: Reduction of MVE is proportional to the
      magnitude of LDL-C lowering across a broad spectrum of on-treatment levels in
      secondary prevention. Statin intensification and add-on treatment with PCSK9
      inhibitors or ezetimibe are associated with significant reduction of
      cardiovascular morbidity in this very high-risk population.

PMID- 29069378
TI  - The effect of a performance-based financing program on HIV and maternal/child
      health services in Mozambique-an impact evaluation.
AB  - Performance-based financing (PBF) is a mechanism by which health providers are
      paid on the basis of outputs or results delivered. A PBF program was implemented
      on the provision of HIV, prevention of mother-to child HIV transmission (PMTCT),
      and maternal/child health (MCH) services in two provinces of Mozambique. A
      retrospective case-control study design was used in which PBF provinces were
      matched with control provinces to evaluate the impact of PBF on 18 indicators.
      Due to regional heterogeneity, we evaluated the intervention sites (North and
      South) separately. Beginning January 2011, 11 quarters (33 months or 2.75 years)
      of data from 134 facilities after matching (84 in the North and 50 in the South)
      were used. Our econometric framework employed a multi-period, multi-group
      difference-in-differences model on data that was matched using propensity
      scoring. The regression design employed a generalized linear mixed model with
      both fixed and random effects, fitted using the seemingly unrelated regression
      technique. PBF resulted in positive impacts on MCH, PMTCT and paediatric HIV
      program outcomes. The majority of the 18 indicators responded to PBF (77% in the
      North and 66% in the South), with at least half of the indicators demonstrating a
      statistically significant increase in average output of more than 50% relative to
      baseline. Excluding pregnant women, the majority of adult HIV treatment
      indicators did not respond to PBF. On average, it took 18 months (six quarters)
      of implementation for PBF to take effect, and impact was generally sustained
      thereafter. Indicators were not sensitive to price, but were inversely correlated
      to the level of effort associated with marginal output. No negative impacts on
      incentivized indicators nor spill-over effects on non-incentivized indicators
      were observed. The PBF program in Mozambique has produced large, sustained
      increases in the provision of PMTCT, paediatric HIV and MCH services. Our results
      demonstrate that PBF is an effective strategy for driving down the HIV epidemic
      and advancing MCH care service delivery as compared with input financing alone.

PMID- 29069379
TI  - Reaction engineering analysis of the autotrophic energy metabolism of Clostridium
      aceticum.
AB  - Acetogenesis with CO2:H2 or CO via the reductive acetyl-CoA pathway does not
      provide any net ATP formation in homoacetogenic bacteria. Autotrophic energy
      conservation is coupled to the generation of chemiosmotic H+ or Na+ gradients
      across the cytoplasm membrane using either a ferredoxin:NAD+ oxidoreductase
      (Rnf), a ferredoxin:H+ oxidoreductase (Ech) or substrate-level phosphorylation
      via cytochromes. The first isolated acetogenic bacterium Clostridium aceticum
      shows both cytochromes and Rnf complex, putting it into an outstanding position.
      Autotrophic batch processes with continuous gas supply were performed in fully
      controlled stirred-tank bioreactors to elucidate energy metabolism of C.
      aceticum. Varying the initial Na+ concentration in the medium showed sodium
      dependent growth of C. aceticum with a growth optimum between 60 and 90 mM Na+.
      The addition of the Na+-selective ionophore ETH2120 or the protonophore CCCP or
      the H+/cation-antiporter monensin revealed that an H+ gradient is used as primary
      energy conservation mechanism, which strengthens the exceptional position of C.
      aceticum as acetogenic bacterium showing an H+-dependent energy conservation
      mechanism as well as Na+-dependent growth.

PMID- 29069380
TI  - Skeletal Microstructure and Estimated Bone Strength Improve Following
      Parathyroidectomy in Primary Hyperparathyroidism.
AB  - Context: High-resolution peripheral quantitative computed tomography (HRpQCT) is
      a noninvasive imaging technology that can provide insight into skeletal
      microstructure and strength. In asymptomatic primary hyperparathyroidism (PHPT),
      HRpQCT imaging has demonstrated both decreased cortical and trabecular indices,
      consistent with evidence for increased fracture risk. There are limited data
      regarding changes in HRpQCT parameters postparathyroidectomy. Objective: To
      evaluate changes in skeletal microstructure by HRpQCT in subjects with PHPT after
      parathyroidectomy. Design: We studied 29 subjects with PHPT (21 women, 8 men)
      with HRpQCT at baseline and 6, 12, 18, and 24 months postparathyroidectomy. Main
      Outcome Measures: Volumetric bone mineral density, microarchitectural indices,
      and finite element analysis at the distal radius and tibia. Results: At both the
      radius and tibia, there were significant improvements in total, cortical, and
      trabecular volumetric bone density as early as 6 months postparathyroidectomy (24
      month values for total volumetric bone density, radius: +2.8 +/- 4%, tibia: +4.4
      +/- 4%; P < 0.0001 for both), cortical thickness (radius: +1.1 +/- 2%, tibia:
      +2.0 +/- 3%; P < 0.01 for both), and trabecular bone volume (radius: +3.8 +/- 5%,
      tibia: +3.2 +/- 4%; P < 0.0001 for both). At both sites, by finite element
      analysis, stiffness and failure load were improved starting at 6 months
      postparathyroidectomy (24-month values for failure load, radius: +6.2 +/- 6%,
      tibia: +4.8 +/- 7%; P < 0.0001 for both). Conclusions: These results provide
      information about skeletal microarchitecture in subjects with PHPT followed
      through 2 years after parathyroidectomy. Estimated bone strength is improved,
      consistent with data showing decreased fracture risk postparathyroidectomy.

PMID- 29069381
TI  - The year 2015-16 in the European Heart Journal-Cardiovascular Imaging. Part II.
AB  - The multi-modality cardiovascular imaging journal, European Heart Journal
      Cardiovascular Imaging, was created in 2012. It has gained an impressive impact
      factor of 5.99 during its first 5 years and is now the most important imaging
      journal in Europe. The most important studies from the journal's fourth and fifth
      years will be highlighted in two reports. Part I of the review will focus on
      studies in myocardial function, myocardial ischaemia, and emerging techniques in
      cardiovascular imaging and Part II will focus on valvular heart diseases, heart
      failure, cardiomyopathies, and congenital heart diseases.

PMID- 29069383
TI  - Effects on nasal airflow and resistance using two different RME appliances: a
      randomized controlled trial.
AB  - Objectives: To evaluate and compare the effects of tooth-borne (TB) and tooth
      bone-borne (TBB) rapid maxillary expansion (RME) on nasal airflow and resistance.
      Material and methods: Fifty-four consecutive patients who met the eligibility
      criteria were recruited from September 2010 to December 2015. Of these 54
      subjects, 40 agreed to participate in the part of the study involving evaluation
      of nasal flow and resistance. The 40 subjects were allocated to either the TB
      group, mean age 9.7 years (SD 1.5), or the TBB group, mean age 10.2 years (SD
      1.4). All subjects performed rhinomanometric registration at baseline (T0), but
      only 30 attended the post-expansion registration (T1), of whom 16 had been
      randomized to the TB group and 14 to the TBB group. The study outcomes, nasal
      airflow and nasal airway resistance, were evaluated with linear regression
      adjusted for baseline variable of the outcome to compare the study groups with
      complete cases strategy as well as after multiple imputation (MI). Randomization:
      Participants were randomly allocated in blocks of different sizes, using the
      concealed allocation principle in a 1:1 ratio. The randomization list was
      computer generated to ensure homogeneity between groups. Blinding: Blinding was
      done only for outcome assessor due to clinical limitations. The care providers at
      the ENT unit who conducted all the rhinomanometry examinations were blinded to
      which group the patients were allocated to. Results: Complete case analysis
      showed significantly higher post-expansion nasal airflow values for the TBB group
      compared with the TB group, mean difference 51.0 cm3/s (P = 0.018). The
      evaluation after MI showed a similar significant mean difference, 52.7 cm3/s (P =
      0.020) in favour of the TBB group when taking into account the missing values
      from the T1 examination. Even reduction in nasal airway resistance showed similar
      pattern in favour of the TBB group. Limitations: Our results represent the short
      term effects. A longer follow-up period would have been preferable. Conclusions:
      The TBB RME induced significantly higher nasal airway flow and lower nasal
      resistance values than TB RME. It might be wiser to use TBB RME in cases with
      constricted maxilla and upper airway obstruction. Registration: This trial was
      not registered in any external sites. Protocol: The protocol was not published
      before trial commencement.

PMID- 29069384
TI  - A Prospective Cohort Study of Prenatal Diethylstilbestrol Exposure and
      Cardiovascular Disease Risk.
AB  - Purpose: Prenatal exposure to diethylstilbestrol (DES), a prototype endocrine
      disrupting chemical, is associated with risk for adverse reproductive outcomes
      and cancer in women. We investigated whether cardiovascular disease (CVD) risk
      might also be greater in women prenatally exposed to DES. Methods: DES-exposed (n
      = 3941) and -unexposed (n = 1705) women participating in the Combined DES Cohort
      Follow-up Study were followed prospectively from 1994 to 2013. Prenatal DES
      exposure (or lack of exposure) was documented in the birth record or physician's
      note. Participants reported by questionnaire any "serious medical conditions
      requiring hospitalization, surgery or long-term treatment," including coronary
      artery disease (CAD), myocardial infarction (MI), and stroke. We sought
      physician's verification of self-reports and identified CVD deaths from the
      National Death Index. Hazard ratios (HRs) with 95% confidence intervals (CIs)
      from Cox proportional hazard regression models estimated associations between DES
      exposure and CVD incidence, adjusted for birth year, original cohort, and
      potential confounders. Results: In comparison of the exposed to the unexposed
      women, the HRs for reported conditions were 1.74 (95% CI, 1.03 to 2.93) for CAD,
      2.20 (95% CI, 1.15 to 4.21) for MI, 1.01 (95% CI, 0.54 to 1.90) for stroke, and
      1.31 (95% CI, 0.93 to 1.86) for the combined conditions (i.e., total CVD). The
      HRs were similar for verified outcomes (CAD, 1.72; MI, 2.67; stroke, 0.92; and
      total CVD, 1.25) and with additional adjustment for hypertension, diabetes, and
      high cholesterol (HRs: CAD, 1.67; MI, 2.04; stroke, 0.96; and total CVD, 1.24).
      Conclusions: These data demonstrate associations in women who have prenatal DES
      exposure with CAD and MI, but not with stroke, which appear to be independent of
      established CVD risk factors.

PMID- 29069382
TI  - Environmental factors influencing the development and spread of antibiotic
      resistance.
AB  - Antibiotic resistance and its wider implications present us with a growing
      healthcare crisis. Recent research points to the environment as an important
      component for the transmission of resistant bacteria and in the emergence of
      resistant pathogens. However, a deeper understanding of the evolutionary and
      ecological processes that lead to clinical appearance of resistance genes is
      still lacking, as is knowledge of environmental dispersal barriers. This calls
      for better models of how resistance genes evolve, are mobilized, transferred and
      disseminated in the environment. Here, we attempt to define the ecological and
      evolutionary environmental factors that contribute to resistance development and
      transmission. Although mobilization of resistance genes likely occurs
      continuously, the great majority of such genetic events do not lead to the
      establishment of novel resistance factors in bacterial populations, unless there
      is a selection pressure for maintaining them or their fitness costs are
      negligible. To enable preventative measures it is therefore critical to
      investigate under what conditions and to what extent environmental selection for
      resistance takes place. In addition, understanding dispersal barriers is not only
      key to evaluate risks, but also to prevent resistant pathogens, as well as novel
      resistance genes, from reaching humans.

PMID- 29069386
TI  - Links between seawater flooding, soil ammonia oxidiser communities and their
      response to changes in salinity.
AB  - Coastal areas worldwide are challenged by climate change-associated increases in
      sea level and storm surge quantities that potentially lead to more frequent
      flooding of soil ecosystems. Currently, little is known of the effects of
      inundation events on microorganisms controlling nitrification in these
      ecosystems. The goal of this study was to investigate the impact of seawater
      flooding on the abundance, community composition and salinity tolerance of soil
      ammonia oxidisers. Topsoil was sampled from three islands flooded at different
      frequencies by the Wadden Sea. Archaeal ammonia oxidiser amoA genes were more
      abundant than their betaproteobacterial counterparts, and the distribution of
      archaeal and bacterial ammonia oxidiser amoA and 16S rRNA gene sequences
      significantly differed between the islands. The findings indicate selection of
      ammonia oxidiser phylotypes with greater tolerance to high salinity and slightly
      alkaline pH (e.g. Nitrosopumilus representatives) in frequently flooded soils. A
      cluster phylogenetically related to gammaproteobacterial ammonia oxidisers was
      detected in all samples analysed in this survey. Nevertheless, no
      gammaprotebacterial amoA genes could be amplified via PCR and only
      betaproteobacterial ammonia oxidisers were detected in enrichment cultures. A
      slurry-based experiment demonstrated the tolerance of both bacterial and archaeal
      ammonia oxidisers to a wide range of salinities (e.g. Wadden Sea water salinity)
      in soil naturally exposed to seawater at a high frequency.

PMID- 29069387
TI  - Functional role of DNA methylation at the FLO1 promoter in budding yeast.
AB  - We have previously reported that the transformation of the budding yeast with
      plasmids encoding the human DNA methyltransferases DNMT1 and DNMT3B cDNAs induces
      the mRNA of flocculin gene FLO1 and the flocculation phenotype. In the present
      study, we evaluated the effect of DNMT inhibitor in the transformed yeasts using
      a FLO1 promoter-based green fluorescent protein (GFP) reporter gene assay. The
      DNMT inhibitor, 5-aza-2?-deoxycytidine (5AZ), decreased GFP fluorescence driven
      by FLO1 promoter in DNMT-genes transformed yeast (DNMT yeast). Surprisingly, the
      GFP activity driven by cytosine-phosphate-guanine (CpG) motif-reduced FLO1
      promoter decreased both in DNMTs gene-transformed and control strains. Yeast
      cells transformed with expression vector encoding a maintenance enzyme DNMT1 cDNA
      showed a flocculation phenotype that was associated with an enhanced mRNA level
      of FLO1. Bisulfite sequencing revealed methylated CpG sites at the FLO1 promoter
      in a control strain not expressing any DNMT transgenes, and no detectable
      methylation at the sites was observed in cells treated with 5AZ. These results
      suggest that the FLO1 promoter is endogenously de novo methylated leading to the
      activation of FLO1 gene transcription. Furthermore, the methylation level at the
      FLO1 promoter is responsible for the significant differences in FLO1 promoter
      driven expression of GFP in DNMT yeast.

PMID- 29069385
TI  - Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies
      Patients With Undiagnosed APS1.
AB  - Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder
      that features autoimmune Addison disease as a major component. Although APS1
      accounts for only a small fraction of all patients with Addison disease, early
      identification of these individuals is vital to prevent the potentially lethal
      complications of APS1. Objective: To determine whether available serological and
      genetic markers are valuable screening tools for the identification of APS1 among
      patients diagnosed with Addison disease. Design: We systematically screened 677
      patients with Addison disease enrolled in the Swedish Addison Registry for
      autoantibodies against interleukin-22 and interferon-alpha4. Autoantibody
      positive patients were investigated for clinical manifestations of APS1,
      additional APS1-specific autoantibodies, and DNA sequence and copy number
      variations of AIRE. Results: In total, 17 patients (2.5%) displayed
      autoantibodies against interleukin-22 and/or interferon-alpha4, of which nine
      were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled
      clinical, genetic, and serological criteria. Hence, we identified four patients
      with undiagnosed APS1 with this screening procedure. Conclusion: We propose that
      patients with Addison disease should be routinely screened for cytokine
      autoantibodies. Clinical or serological support for APS1 should warrant DNA
      sequencing and copy number analysis of AIRE to enable early diagnosis and
      prevention of lethal complications.

PMID- 29069388
TI  - The secreted polyketide boydone A is responsible for the anti-Staphylococcus
      aureus activity of Scedosporium boydii.
AB  - Usually living as a soil saprophyte, the filamentous fungus Scedosporium boydii
      may also cause various infections in human. Particularly, it is one of the major
      causative agents of fungal colonization of the airways in patients with cystic
      fibrosis (CF). To compete with other microorganisms in the environment, fungi
      have evolved sophisticated strategies, including the production of secondary
      metabolites with antimicrobial activity that may also help them to establish
      successfully within the respiratory tract of receptive hosts. Here, the culture
      filtrate from a human pathogenic strain of S. boydii was investigated searching
      for an antibacterial activity, mainly against the major CF bacterial pathogens. A
      high antibacterial activity against Staphylococcus aureus, including methicillin
      resistant strains of this species, was observed. Bio-guided fractionation and
      analysis of the active fractions by nuclear magnetic resonance or by high
      performance liquid chromatography and high-resolution electrospray ionization
      mass spectrometry allowed us to identify boydone A as responsible for this
      antibacterial activity. Together, these results suggest that this six-membered
      cyclic polyketide could be one of the virulence factors of the fungus. Genes
      involved in the synthesis of this secreted metabolite are currently being
      identified in order to confirm the role of this polyketide in pathogenesis.

PMID- 29069389
TI  - Spatial and Temporal Scales of Range Expansion in Wild Phaseolus vulgaris.
AB  - The wild progenitor of common-bean has an exceptionally large distribution from
      northern Mexico to northwestern Argentina, unusual among crop wild progenitors.
      This research sought to document major events of range expansion that led to this
      distribution and associated environmental changes. Through the use of genotyping
      by-sequencing (~20,000 SNPs) and geographic information systems applied to a
      sample of 246 accessions of wild Phaseolus vulgaris, including 157 genotypes of
      the Mesoamerican, 77 of the southern Andean, and 12 of the Northern Peru-Ecuador
      gene pools, we identified five geographically distinct subpopulations. Three of
      these subpopulations belong to the Mesoamerican gene pool (Northern and Central
      Mexico, Oaxaca, and Southern Mexico, Central America and northern South America)
      and one each to the Northern Peru-Ecuador (PhI) and the southern Andean gene
      pools. The five subpopulations were distributed in different floristic provinces
      of the Neotropical seasonally dry forest and showed distinct distributions for
      temperature and rainfall resulting in decreased local potential
      evapotranspiration (PhI and southern Andes groups) compared with the two Mexican
      groups. Three of these subpopulations represent long-distance dispersal events
      from Mesoamerica into Northern Peru-Ecuador, southern Andes, and Central America
      and Colombia, in chronological order. Of particular note is that the dispersal to
      Northern Peru-Ecuador markedly predates the dispersal to the southern Andes (~400
      vs. ~100 ky), consistent with the ancestral nature of the phaseolin seed protein
      and chloroplast sequences observed in the PhI group. Seed dispersal in common
      bean can be, therefore, described at different spatial and temporal scales, from
      localized, annual seed shattering to long-distance, evolutionarily rare
      migration.

PMID- 29069390
TI  - CRIMEtoYHU: a new web tool to develop yeast-based functional assays for
      characterizing cancer-associated missense variants.
AB  - Evaluation of the functional impact of cancer-associated missense variants is
      more difficult than for protein-truncating mutations and consequently standard
      guidelines for the interpretation of sequence variants have been recently
      proposed. A number of algorithms and software products were developed to predict
      the impact of cancer-associated missense mutations on protein structure and
      function. Importantly, direct assessment of the variants using high-throughput
      functional assays using simple genetic systems can help in speeding up the
      functional evaluation of newly identified cancer-associated variants. We
      developed the web tool CRIMEtoYHU (CTY) to help geneticists in the evaluation of
      the functional impact of cancer-associated missense variants. Humans and the
      yeast Saccharomyces cerevisiae share thousands of protein-coding genes although
      they have diverged for a billion years. Therefore, yeast humanization can be
      helpful in deciphering the functional consequences of human genetic variants
      found in cancer and give information on the pathogenicity of missense variants.
      To humanize specific positions within yeast genes, human and yeast genes have to
      share functional homology. If a mutation in a specific residue is associated with
      a particular phenotype in humans, a similar substitution in the yeast counterpart
      may reveal its effect at the organism level. CTY simultaneously finds yeast
      homologous genes, identifies the corresponding variants and determines the
      transferability of human variants to yeast counterparts by assigning a
      reliability score (RS) that may be predictive for the validity of a functional
      assay. CTY analyzes newly identified mutations or retrieves mutations reported in
      the COSMIC database, provides information about the functional conservation
      between yeast and human and shows the mutation distribution in human genes. CTY
      analyzes also newly found mutations and aborts when no yeast homologue is found.
      Then, on the basis of the protein domain localization and functional conservation
      between yeast and human, the selected variants are ranked by the RS. The RS is
      assigned by an algorithm that computes functional data, type of mutation,
      chemistry of amino acid substitution and the degree of mutation transferability
      between human and yeast protein. Mutations giving a positive RS are highly
      transferable to yeast and, therefore, yeast functional assays will be more
      predictable. To validate the web application, we have analyzed 8078 cancer
      associated variants located in 31 genes that have a yeast homologue. More than
      50% of variants are transferable to yeast. Incidentally, 88% of all transferable
      mutations have a reliability score >0. Moreover, we analyzed by CTY 72
      functionally validated missense variants located in yeast genes at positions
      corresponding to the human cancer-associated variants. All these variants gave a
      positive RS. To further validate CTY, we analyzed 3949 protein variants (with
      positive RS) by the predictive algorithm PROVEAN. This analysis shows that yeast
      based functional assays will be more predictable for the variants with positive
      RS. We believe that CTY could be an important resource for the cancer research
      community by providing information concerning the functional impact of specific
      mutations, as well as for the design of functional assays useful for decision
      support in precision medicine.

PMID- 29069391
TI  - Dimensions and intensity of inter-professional teamwork in primary care: evidence
      from five international jurisdictions.
AB  - Background: Inter-professional teamwork in primary care settings offers potential
      benefits for responding to the increasing complexity of patients' needs. While it
      is a central element in many reforms to primary care delivery, implementing inter
      professional teamwork has proven to be more challenging than anticipated.
      Objective: The objective of this study was to better understand the dimensions
      and intensity of teamwork and the developmental process involved in creating
      fully integrated teams. Methods: Secondary analyses of qualitative and
      quantitative data from completed studies conducted in Australia, Canada and USA.
      Case studies and matrices were used, along with face-to-face group retreats,
      using a Collaborative Reflexive Deliberative Approach. Results: Four dimensions
      of teamwork were identified. The structural dimension relates to human resources
      and mechanisms implemented to create the foundations for teamwork. The
      operational dimension relates to the activities and programs conducted as part of
      the team's production of services. The relational dimension relates to the
      relationships and interactions occurring in the team. Finally, the functional
      dimension relates to definitions of roles and responsibilities aimed at
      coordinating the team's activities as well as to the shared vision, objectives
      and developmental activities aimed at ensuring the long-term cohesion of the
      team. There was a high degree of variation in the way the dimensions were
      addressed by reforms across the national contexts. Conclusion: The framework
      enables a clearer understanding of the incremental and iterative aspects that
      relate to higher achievement of teamwork. Future reforms of primary care need to
      address higher-level dimensions of teamwork to achieve its expected outcomes.

PMID- 29069392
TI  - Biomedical Enhancement of Warfighters and the Legal Protection of Military
      Medical Personnel in Armed Conflict.
AB  - Under international law, military medical personnel and facilities must be
      respected and protected in the event of an armed conflict. This special status
      only applies to personnel and facilities exclusively engaged in certain
      enumerated medical duties, especially the treatment of the wounded and sick, and
      the prevention of disease. Military medical personnel have, however, been called
      upon to engage in the biomedical enhancement of warfighters, as exemplified by
      the supply of central nervous system stimulants as a fatigue countermeasure. This
      article argues that international law of armed conflict does not recognise human
      enhancement as a medical duty, and that engaging in enhancement that is harmful
      to the enemy results in the loss of special protection normally enjoyed by
      military medical personnel and units.

PMID- 29069393
TI  - Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and
      Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.
AB  - Sclerostin antibody (Scl-Ab) restored bone mass and strength in the
      ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral
      density (BMD) and decreased skeletal fragility fracture risk have been reported
      in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen
      leads to rapid decreases in BMD and an increased risk of fragility fractures. We
      hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused
      by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis.
      We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX)
      subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n
      = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the
      lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed
      that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and
      femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these
      sites increased significantly with Scl-Ab to levels matching those of sham
      operated controls and correlated positively with improvements in bone mineral
      content, demonstrating bone quality maintenance. Dynamic histomorphometry of the
      tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab
      significantly increased bone formation on periosteal, endocortical, and
      trabecular surfaces and significantly decreased bone resorption on endocortical
      and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and
      decreasing bone resorption led to restoration of bone mass and strength in
      androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab
      as a potential therapeutic agent for osteoporosis in men.

PMID- 29069394
TI  - Exploring completeness in clinical data research networks with DQe-c.
AB  - Objective: To provide an open source, interoperable, and scalable data quality
      assessment tool for evaluation and visualization of completeness and conformance
      in electronic health record (EHR) data repositories. Materials and Methods: This
      article describes the tool's design and architecture and gives an overview of its
      outputs using a sample dataset of 200 000 randomly selected patient records with
      an encounter since January 1, 2010, extracted from the Research Patient Data
      Registry (RPDR) at Partners HealthCare. All the code and instructions to run the
      tool and interpret its results are provided in the Supplementary Appendix.
      Results: DQe-c produces a web-based report that summarizes data completeness and
      conformance in a given EHR data repository through descriptive graphics and
      tables. Results from running the tool on the sample RPDR data are organized into
      4 sections: load and test details, completeness test, data model conformance
      test, and test of missingness in key clinical indicators. Discussion: Open
      science, interoperability across major clinical informatics platforms, and
      scalability to large databases are key design considerations for DQe-c. Iterative
      implementation of the tool across different institutions directed us to improve
      the scalability and interoperability of the tool and find ways to facilitate
      local setup. Conclusion: EHR data quality assessment has been hampered by
      implementation of ad hoc processes. The architecture and implementation of DQe-c
      offer valuable insights for developing reproducible and scalable data science
      tools to assess, manage, and process data in clinical data repositories.

PMID- 29069395
TI  - Polymorphism in the regulatory regions of genes CgYPS1 and CgYPS7 encoding
      yapsins in Candida glabrata is associated with changes in expression levels.
AB  - Candida glabrata is an opportunistic fungus infecting mainly immunocompromised
      people. Its adherence capacity and exoenzymes contribute to damaging host cells.
      In particular, the yapsins are a family of aspartyl proteases involved in
      maturation of proteins and cell wall function, and yapsins 1 and 7, respectively
      encoded by genes CgYPS1 and CgYPS7, are potential virulence factors. In this
      study, the polymorphism of regulatory regions and the expression profiles of both
      genes were compared in C. glabrata clinical strains. The sequence analysis of
      regulatory regions revealed that the distribution of transcription factor binding
      sites (TFBSs) was similar, although some TFBSs were not universally distributed.
      The quantita-tive expression of CgYPS1 and CgYPS7 genes of different C. glabrata
      strains in rich and poor media was estimated by RT-qPCR. The primary sequences of
      genes CgYPS1 and CgYPS7 of C. glabrata strains were highly conserved among
      different strains, but the regulatory regions were polymorphic, harboring
      different TFBS arrays, and showing differential expression profiles.

PMID- 29069397
TI  - Radiation-related thyroid autoimmunity and dysfunction.
AB  - The thyroid gland is vulnerable not only to external radiation but also to
      internal radiation, because the thyroid cells can incorporate radioactive iodine
      when synthesizing thyroid hormones. Since radiation-induction of thyroid
      neoplasia, including thyroid cancer, is well recognized, the data on radiation
      related thyroid autoimmunity and dysfunction are summarized and reviewed. High
      dose irradiation, irrespective of being external or internal, is strongly
      associated with a risk of hypothyroidism (with the prevalence ranging from 2.4%
      to 31%) and of Graves' hyperthyroidism (with the prevalence being up to 5%). It
      is easy to understand that high-dose irradiation induces hypothyroidism with some
      frequency, because high-dose irradiation destroys the thyroid gland. On the other
      hand, the basis for development of hyperthyroidism is mechanistically unclear,
      and it is merely speculative that autoantigens may be released from damaged
      thyroid glands and recognized by the immune system, leading to the development of
      anti-thyrotropin receptor antibodies and Graves' hyperthyroidism in subjects who
      are immunologically predisposed to this ailment. In contrast, the data on
      moderate to low-dose irradiation on thyroid autoimmunity and dysfunction are
      inconsistent. Although it is difficult to draw a definitive conclusion, some data
      may suggest a transient effect of moderate- to low-dose irradiation on
      hypothyroidism and autoimmune thyroiditis, implying that the effect, if it
      exists, is reversible. Finally, no report has shown a statistically significant
      increase in the prevalence of moderate- to low-dose irradiation-induced Graves'
      hyperthyroidism.

PMID- 29069398
TI  - Metabarcoding Analyses Enable Differentiation of Both Interspecific Assemblages
      and Intraspecific Divergence in Habitats With Differing Management Practices.
AB  - Spatial and temporal collections provide important data on the distribution and
      dispersal of species. Regional-scale monitoring invariably involves hundreds of
      thousands of samples, the identification of which is costly in both time and
      money. In this respect, metabarcoding is increasingly seen as a viable
      alternative to traditional morphological identification, as it eliminates the
      taxonomic bottleneck previously impeding such work. Here, we assess whether
      terrestrial arthropods collected from 12 pitfall traps in two farms of a coffee
      (Coffea arabica L.) growing region of Sao Paulo State, Brazil could differentiate
      the two locations. We sequenced a portion of the cytochrome oxidase 1 region from
      minimally processed pools of samples and assessed inter- and intraspecific
      parameters across the two locations. Our sequencing was sufficient to
      circumscribe the overall diversity, which was characterized by few dominant taxa,
      principally small Coleoptera species and Collembola. Thirty-four operational
      taxonomic units were detected and of these, eight were present in significantly
      different quantities between the two farms. Analysis of community-wide Beta
      diversity grouped collections based on farm provenance. Moreover, haplotype-based
      analyses for a species of Xyleborus beetle showed that there is significant
      population genetic structuring between the two farms, suggesting limited
      dispersal. We conclude that metabarcoding can provide important management input
      and, considering the rapidly declining cost of sequencing, suggest that large
      scale monitoring is now feasible and can identify both the taxa present as well
      as contribute information about genetic diversity of focal species.

PMID- 29069396
TI  - Presence of tau pathology within foetal neural allografts in patients with
      Huntington's and Parkinson's disease.
AB  - Cell replacement has been explored as a therapeutic strategy to repair the brain
      in patients with Huntington's and Parkinson's disease. Post-mortem evaluations of
      healthy grafted tissue in such cases have revealed the development of Huntington-
      or Parkinson-like pathology including mutant huntingtin aggregates and Lewy
      bodies. An outstanding question remains if tau pathology can also be seen in
      patients with Huntington's and Parkinson's disease who had received foetal neural
      allografts. This was addressed by immunohistochemical/immunofluorescent stainings
      performed on grafted tissue of two Huntington's disease patients, who came to
      autopsy 9 and 12 years post-transplantation, and two patients with Parkinson's
      disease who came to autopsy 18 months and 16 years post-transplantation. We show
      that grafts also contain tau pathology in both types of transplanted patients. In
      two patients with Huntington's disease, the grafted tissue showed the presence of
      hyperphosphorylated tau [both AT8 (phospho-tau Ser202 and Thr205) and CP13
      (pSer202) immunohistochemical stainings] pathological inclusions, neurofibrillary
      tangles and neuropil threads. In patients with Parkinson's disease, the grafted
      tissue was characterized by hyperphosphorylated tau (AT8; immunofluorescent
      staining) pathological inclusions, neurofibrillary tangles and neuropil threads
      but only in the patient who came to autopsy 16 years post-transplantation.
      Abundant tau-related pathology was observed in the cortex and striatum of all
      cases studied. While the striatum of the grafted Huntington's disease patient
      revealed an equal amount of 3-repeat and 4-repeat isoforms of tau, the grafted
      tissue showed elevated 4-repeat isoforms by western blot. This suggests that
      transplants may have acquired tau pathology from the host brain, although another
      possibility is that this was due to acceleration of ageing. This finding not only
      adds to the recent reports that tau pathology is a feature of these
      neurodegenerative diseases, but also that tau pathology can manifest in healthy
      neural tissue transplanted into the brains of patients with two distinct
      neurodegenerative disorders.

PMID- 29069399
TI  - A meta-analysis of continuous positive airway pressure therapy in prevention of
      cardiovascular events in patients with obstructive sleep apnoea.
AB  - Aims: To assess whether continuous positive airway pressure (CPAP) therapy
      reduces major adverse cardiovascular events (MACE) in patients with moderate-to
      severe obstructive sleep apnoea (OSA). Methods and results: A total of 235
      articles were recovered using MEDLINE, EMBASE and Cochrane library (inception
      December 2016) and references contained in the identified articles. Seven
      randomized controlled trials (RCTs) were selected for final analysis. Analysis of
      4268 patients demonstrated non-significant 26% relative risk reduction in MACE
      with CPAP [risk ratio (RR) 0.74; 95% confidence interval (CI) 0.47-1.17; P =
      0.19, I2 = 48%]. A series of sensitivity analyses suggested that increased CPAP
      usage time yielded significant risk reduction in MACE. and stroke. Subgroup
      analysis revealed that CPAP adherence time >=4 hours (h)/night reduced the risk
      of MACE by 57% (RR 0.43; 95% CI 0.23-0.80; P = 0.01, I2 = 0%). CPAP therapy
      showed no beneficial effect on myocardial infarction (MI), all-cause mortality,
      atrial fibrillation/flutter (AF), or heart failure (HF) (P > 0.05). CPAP had
      positive effect on mood and reduced the daytime sleepiness [Epworth Sleepiness
      Scale (ESS): mean difference (MD) -2.50, 95% CI - 3.62, -1.39; P < 0.001, I2 =
      81%]. Conclusion: CPAP therapy might reduce MACE and stroke among subjects with
      CPAP time exceeding 4 h/night. Additional randomized trials mandating adequate
      CPAP time adherence are required to confirm this impression.

PMID- 29069400
TI  - Safety, tolerability and pharmacokinetics of 21 day multiple oral administration
      of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects.
AB  - Background: LCB01-0371 is a new oxazolidinone antibiotic, which targets most Gram
      positive organisms. High rates of adverse reactions including myelosuppression
      have been reported for existing oxazolidinones, limiting their long-term use.
      Objectives: The safety, tolerability and pharmacokinetics (PK) of 21 day multiple
      oral administrations of LCB01-0371 in healthy male subjects (clinicaltrials.gov:
      NCT02540460) were investigated. Methods: In this randomized, double-blind,
      placebo-controlled study, subjects received 800 mg of LCB01-0371 once or twice
      daily or 1200 mg of LCB01-0371 twice-daily for 21 days in a fasting state. Safety
      and tolerability profiles including laboratory tests were evaluated during the
      study and on a post-study visit and the results were analysed using repeated
      measures analysis of variance (RM-ANOVA). Serial blood samples for PK analysis
      were collected up to 12 h after dosing on day 21. Results: A total of 40 subjects
      were enrolled and 34 subjects completed the study. Two subjects dropped out
      according to stopping rules. In the 1200 mg twice-daily dose group, the absolute
      value of red blood cell count, haematocrit and haemoglobin decreased by 500 *
      106/L (6.5%), 4.5% (6.8%) and 1.6 g/dL (6.9%), respectively, after 21 day
      administrations of LCB01-0371. However, mean relative changes from baseline of
      all haematology values were not significantly different among doses, including
      placebo (all, P < 0.05). PK profiles of LCB01-0371 in the dose range of 800 mg
      once daily to 1200 mg twice daily were consistent with previous studies.
      Conclusions: LCB01-0371 is well tolerated in healthy male subjects with
      comparable haematology profiles to placebo, after multiple doses of up to 1200 mg
      twice daily for 21 days.

PMID- 29069401
TI  - Large-Scale Climate Effects Meet an Amazonian Butterfly: Which Population
      Parameters Respond to El Nino?
AB  - One of the most tangible outcomes of climate change is change in the frequency of
      El Nino/La Nina events. They have a large impact on rainfall in the Western
      hemisphere, but their impact on tropical fauna is largely unknown. A decade long
      capture-mark-recapture study of the widespread Ecuadorian butterfly Nessaea
      hewitsoni (Felder & Felder) from an intact forest allowed us to analyze patterns
      of monthly and seasonal population dynamics before, during, and after an El Nino
      event. El Nino events did not affect long-term population size, but a 5-month
      delayed El Nino led to temporary emigration of females, with their subsequent
      return. Increased rainfall correlated with reduced survival in both sexes, but
      this effect was twice as strong in females. This investigation is the longest,
      continuous population study on any Neotropical insect species. Though we sampled
      on a modest scale, the magnitude of El Nino events suggests that our findings
      likely reflect insect population responses across a much larger portion of
      Amazonian forests. This study underscores the importance of analyzing multiple,
      interacting population parameters beyond local abundance in order to understand
      the biotic responses to El Nino and climate change in tropical systems. Had our
      analyses not included temporary emigration, no effect would have been detected
      because El Nino did not affect local population abundance.

PMID- 29069402
TI  - SEECancer: a resource for somatic events in evolution of cancer genome.
AB  - Cancer cells progressively evolve from a premalignant to a malignant state, which
      is driven by accumulating somatic alterations that confer normal cells a fitness
      advantage. Improvements in high-throughput sequencing techniques have led to an
      increase in construction of tumor phylogenetics and identification of somatic
      driver events that specifically occurred in different tumor progression stages.
      Here, we developed the SEECancer database (http://biocc.hrbmu.edu.cn/SEECancer),
      which aims to present the comprehensive cancer evolutionary stage-specific
      somatic events (including early-specific, late-specific, relapse-specific,
      metastasis-specific, drug-resistant and drug-induced genomic events) and their
      temporal orders. By manually curating over 10 000 published articles, 1231
      evolutionary stage-specific genomic events and 5772 temporal orders involving 82
      human cancers and 23 tissue origins were collected and deposited in the SEECancer
      database. Each entry contains the somatic event, evolutionary stage, cancer type,
      detection approach and relevant evidence. SEECancer provides a user-friendly
      interface for browsing, searching and downloading evolutionary stage-specific
      somatic events and temporal relationships in various cancers. With increasing
      attention on cancer genome evolution, the necessary information in SEECancer will
      facilitate understanding of cancer etiology and development of evolutionary
      therapeutics, and help clinicians to discover biomarkers for monitoring tumor
      progression.

PMID- 29069403
TI  - PLAZA 4.0: an integrative resource for functional, evolutionary and comparative
      plant genomics.
AB  - PLAZA (https://bioinformatics.psb.ugent.be/plaza) is a plant-oriented online
      resource for comparative, evolutionary and functional genomics. The PLAZA
      platform consists of multiple independent instances focusing on different plant
      clades, while also providing access to a consistent set of reference species.
      Each PLAZA instance contains structural and functional gene annotations, gene
      family data and phylogenetic trees and detailed gene colinearity information. A
      user-friendly web interface makes the necessary tools and visualizations
      accessible, specific for each data type. Here we present PLAZA 4.0, the latest
      iteration of the PLAZA framework. This version consists of two new instances
      (Dicots 4.0 and Monocots 4.0) providing a large increase in newly available
      species, and offers access to updated and newly implemented tools and
      visualizations, helping users with the ever-increasing demands for complex and in
      depth analyzes. The total number of species across both instances nearly doubles
      from 37 species in PLAZA 3.0 to 71 species in PLAZA 4.0, with a much broader
      coverage of crop species (e.g. wheat, palm oil) and species of evolutionary
      interest (e.g. spruce, Marchantia). The new PLAZA instances can also be accessed
      by a programming interface through a RESTful web service, thus allowing
      bioinformaticians to optimally leverage the power of the PLAZA platform.

PMID- 29069404
TI  - Biofilm-based photobioreactors: their design and improving productivity through
      efficient supply of dissolved inorganic carbon.
AB  - The potential of biofilm-based photobioreactors (PBRs) for various applications
      has long been recognized, and various types of biofilm-based PBRs have been
      developed for different applications. Compared to suspension-based PBR reactors,
      biofilm-based systems offer several advantages, including a significantly higher
      biomass concentration. However, due to the immobilization of the cells, in
      contrast to suspension-based systems, dissolved inorganic carbon (DIC) has to be
      transferred into the biofilm for consumption. Thus, to ensure efficient operation
      of these systems under a given lighting scheme (e.g. depending on geographical
      location), availability of DIC should be optimized. To achieve this, the dynamics
      of DIC inside the various biofilm-based PBRs, as well as the operational
      principles of these PBRs, need to be understood. The mini-review summarizes the
      designs of existing biofilm-based PBRs and reviews previous studies on DIC
      dynamics in various biofilms. Strategies to enhance DIC availability for the
      immobilized cells in biofilm-based PBRs are also discussed.

PMID- 29069405
TI  - Structural analysis of neutral glycosphingolipids from the silkworm Bombyx mori
      and the difference in ceramide composition between larvae and pupae.
AB  - Glycosphingolipids (GSLs) from the silkworm Bombyx mori were identified and GSL
      expression patterns between larvae and pupae were compared. The structural
      analysis of neutral GSLs from dried pupae revealed the following predominant
      species: Glcbeta1Cer, Manbeta4Glcbeta1Cer, GlcNAcbeta3Manbeta4Glcbeta1Cer,
      Galbeta3Manbeta4Glcbeta1Cer, GalNAcalpha4Galbeta3Manbeta4Glcbeta1Cer,
      GlcNAcbeta3Galbeta3Manbeta4Glcbeta1Cer, Galalpha4Galbeta3Manbeta4Glcbeta1Cer and
      (GalNAcalpha4)1-4 GalNAcalpha4Galbeta3Manbeta4Glcbeta1Cer. Lin-ear elongation of
      alpha4-GalNAc was observed at the non-reducing end of Galbeta3Manbeta4Glcbeta1Cer
      with up to five GalNAc repeats. The arthro-series GSL
      GlcNAcbeta3Manbeta4Glcbeta1Cer, a characteristic GSL-glycan sequence of other
      Arthropoda, was detected in silkworms. The main ceramide species in each purified
      GSL fraction were h20:0-d14:1 and h22:0-d14:1. GSL expression patterns in larvae
      and pupae were compared using thin-layer chromatography, which demonstrated
      differences among acidic, polar and neutral GSL fractions, while the zwitterionic
      fraction showed no difference. Neutral GSLs such as ceramides di-, tri- and
      tetrasaccharides in larvae showed less abundant than those in pupae. MALDI-TOF MS
      analysis revealed that larval GSLs contained four types of ceramide species,
      whereas pupal GSLs contained only two types. The structural analysis of neutral
      GSLs from silkworms revealed a novel series of GSLs. The comparison of GSL
      expression patterns between larvae and pupae demonstrated differences in several
      fractions. Alterations in GSL ceramide composition between larvae and pupae were
      observed by MALDI-TOF MS analysis.

PMID- 29069406
TI  - Spatio-temporal models to determine association between Campylobacter cases and
      environment.
AB  - Background: Campylobacteriosis is a major cause of gastroenteritis in the UK, and
      although 70% of cases are associated with food sources, the remainder are
      probably associated with wider environmental exposure. Methods: In order to
      investigate wider environmental transmission, we conducted a spatio-temporal
      analysis of the association of human cases of Campylobacter in the Tyne catchment
      with weather, climate, hydrology and land use. A hydrological model was used to
      predict surface-water flow in the Tyne catchment over 5 years. We analysed
      associations between population-adjusted Campylobacter case rate and
      environmental factors hypothesized to be important in disease using a two-stage
      modelling framework. First, we investigated associations between temporal
      variation in case rate in relation to surface-water flow, temperature,
      evapotranspiration and rainfall, using linear mixed-effects models. Second, we
      used the random effects for the first model to quantify how spatial variation in
      static landscape features of soil and land use impacted on the likely differences
      between subcatchment associations of case rate with the temporal variables.
      Results: Population-adjusted Campylobacter case rates were associated with
      periods of high predicted surface-water flow, and during above average
      temperatures. Subcatchments with cattle on stagnogley soils, and to a lesser
      extent sheep plus cattle grazing, had higher Campylobacter case rates.
      Conclusions: Areas of stagnogley soils with mixed livestock grazing may be more
      vulnerable to both Campylobacter spread and exposure during periods of high
      rainfall, with resultant increased risk of human cases of the disease.

PMID- 29069407
TI  - Reimagining infertility: a critical examination of fertility norms, geopolitics
      and survey bias.
AB  - While it is estimated that 15% of couples worldwide are infertile, this figure
      hinges critically on the quality, inclusiveness and availability of infertility
      data sources. Current infertility data and statistics fail to account for the
      infertility experiences of some social groups. We identify these people as the
      invisible infertile, and refer to their omission from infertility data and
      statistics-whether intentional or unintentional-as the process of
      invisibilization. We identify two processes through which invisibilization in
      survey data is produced: sampling, with focus on exclusionary definitions of the
      population at-risk, and survey instrument design, with focus on skip patterns and
      question wording. Illustrative examples of these processes are drawn from the
      Integrated Fertility Survey Series and the Demographic and Health Surveys.
      Empirical research is not designed in an objective vacuum. Rather, survey
      instruments and sampling techniques are shaped and influenced by the
      sociocultural norms and geopolitical context of the time and place in which they
      are created and conducted, reflecting broader social beliefs about family
      building and reproduction. Furthermore, population policy singularly aimed at
      curbing overpopulation in high fertility parts of the world limits the type of
      reproduction data collected, effectively rendering the infertility of some groups
      epidemiologically unfathomable. In light of these sociocultural and geopolitical
      forces, many marginalized groups are missing from reproductive health (RH)
      statistics. The omission of entire groups from the scientific discourse casts
      doubt on the quality of research questions, validity of the analytic tools, and
      accuracy of scientific findings. Invisibility may also misguide evidence-based RH
      and family planning policies and deter equitable access to reproductive
      healthcare for some social groups, perpetuating social inequalities.

PMID- 29069409
TI  - Initial 2-year results of CardioCel(r) patch implantation in children.
AB  - OBJECTIVES: We present the initial 2-year results of CardioCel(r) patch (Admedus
      Regen Pty Ltd, Perth, WA, Australia) implantation in paediatric patients with
      congenital heart diseases. METHODS: This was a single-centre retrospective study
      with prospectively collected data of all patients aged 18 years and under
      operated for congenital heart disease. The patch was introduced in 2014, with
      clinical practice committee approval and a special consent in case of an Ozaki
      procedure. Standard follow-up was performed with systematic clinical exams and
      echocardiograms. In case of reoperation or graft failure, the patch was removed
      and sent for a histological examination. RESULTS: Between March 2014 and April
      2016, 101 patients had surgical repair using a CardioCel patch. The mean age was
      22 (+/-36.3) months, and the mean weight was 9.7 (+/-10.3) kg. No infections and
      no intraoperative implantation difficulties were associated with the patch. The
      median follow-up period was 212 (range 4-726) days. The overall 30-day
      postoperative mortality was 3.8% (n = 4), none of which were related to graft
      failure. Five children were reoperated because of graft failure, 4 of whom had
      the patch implanted for aortic and were aged less than 10 days. The indications
      for patch implantation in the aortic position were aortopulmonary window, truncus
      arteriosus, coarctation and aortic arch hypoplasia repair. The median time
      between the first and the second operation for graft failure was 245 (range 5
      480) days. CONCLUSIONS: Our experience shows that the patch is well tolerated in
      the septal, valvar and pulmonary artery positions. However, we experienced graft
      failures in infants in the aortic position.

PMID- 29069408
TI  - Asialoglycoprotein receptor 1 mediates productive uptake of N-acetylgalactosamine
      conjugated and unconjugated phosphorothioate antisense oligonucleotides into
      liver hepatocytes.
AB  - Antisense oligonucleotide (ASO) therapeutics show tremendous promise for the
      treatment of previously intractable human diseases but to exert their effects on
      cellular RNA processing they must first cross the plasma membrane by endocytosis.
      The conjugation of ASOs to a receptor ligand can dramatically increase their
      entry into certain cells and tissues, as demonstrated by the implementation of N
      acetylgalactosamine (GalNAc)-conjugated ASOs for Asialoglycoprotein Receptor
      (ASGR)-mediated uptake into liver hepatocytes. We compared the internalization
      and activity of GalNAc-conjugated ASOs and their parents in endogenous ASGR
      expressing cells and were able to recapitulate hepatocyte ASO uptake and activity
      in cells engineered to heterologously express the receptor. We found that the
      minor receptor subunit, ASGR2, is not required for effective in vitro or in vivo
      uptake of GalNAc-conjugated ASO and that the major subunit, ASGR1, plays a small
      but significant role in the uptake of unconjugated phosphorothioate ASOs into
      hepatocytes. Moreover, our data demonstrates there is a large excess capacity of
      liver ASGR for the effective uptake of GalNAc-ASO conjugates, suggesting broad
      opportunities to exploit receptors with relatively moderate levels of expression.

PMID- 29069410
TI  - Protein kinase C in fungi-more than just cell wall integrity.
AB  - Human protein kinase C (PKC) isoforms have been implicated in diseases such as
      Alzheimer's, diabetes and cancers. In contrast to mammals, which have at least
      nine genes, fungi have only one or two. The yeast Saccharomyces cerevisiae
      produces only a single Pkc1 and is employed in the study of specific human
      isozymes, including their susceptibility to pharmacological drugs. Vice versa,
      the domain structure and regulation of yeast and other fungal PKCs yield insights
      into the function of human isozymes. Therefore, human PKCs are briefly reviewed
      herein and related to the yeast enzyme. The latter was originally implicated in
      the regulation of cell wall synthesis through a conserved MAP kinase pathway, but
      many more targets have now been described in S. cerevisiae and other fungi. These
      implicate PKC in the control of such diverse processes as the organization of the
      actin cytoskeleton, autophagy and apoptosis, nutrient sensing and ribosome
      biogenesis, cell cycle control, cytokinesis and genetic stability. PKC is a
      promising target for the development of antifungal drugs against pathogenic fungi
      such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus.
      Thus, fungal PKCs are drawing increased attention and the accumulating literature
      on the enzymes from different species is summarized herein.

PMID- 29069412
TI  - MEBS, a software platform to evaluate large (meta)genomic collections according
      to their metabolic machinery: unraveling the sulfur cycle.
AB  - The increasing number of metagenomic and genomic sequences has dramatically
      improved our understanding of microbial diversity, yet our ability to infer
      metabolic capabilities in such datasets remains challenging. We describe the
      Multigenomic Entropy Based Score pipeline (MEBS), a software platform designed to
      evaluate, compare, and infer complex metabolic pathways in large "omic" datasets,
      including entire biogeochemical cycles. MEBS is open source and available through
      https://github.com/eead-csic-compbio/metagenome_Pfam_score. To demonstrate its
      use, we modeled the sulfur cycle by exhaustively curating the molecular and
      ecological elements involved (compounds, genes, metabolic pathways, and microbial
      taxa). This information was reduced to a collection of 112 characteristic Pfam
      protein domains and a list of complete-sequenced sulfur genomes. Using the
      mathematical framework of relative entropy (H?), we quantitatively measured the
      enrichment of these domains among sulfur genomes. The entropy of each domain was
      used both to build up a final score that indicates whether a (meta)genomic sample
      contains the metabolic machinery of interest and to propose marker domains in
      metagenomic sequences such as DsrC (PF04358). MEBS was benchmarked with a dataset
      of 2107 non-redundant microbial genomes from RefSeq and 935 metagenomes from MG
      RAST. Its performance, reproducibility, and robustness were evaluated using
      several approaches, including random sampling, linear regression models, receiver
      operator characteristic plots, and the area under the curve metric (AUC). Our
      results support the broad applicability of this algorithm to accurately classify
      (AUC = 0.985) hard-to-culture genomes (e.g., Candidatus Desulforudis
      audaxviator), previously characterized ones, and metagenomic environments such as
      hydrothermal vents, or deep-sea sediment. Our benchmark indicates that an entropy
      based score can capture the metabolic machinery of interest and can be used to
      efficiently classify large genomic and metagenomic datasets, including
      uncultivated/unexplored taxa.

PMID- 29069413
TI  - WormBase 2017: molting into a new stage.
AB  - WormBase (http://www.wormbase.org) is an important knowledge resource for
      biomedical researchers worldwide. To accommodate the ever increasing amount and
      complexity of research data, WormBase continues to advance its practices on data
      acquisition, curation and retrieval to most effectively deliver comprehensive
      knowledge about Caenorhabditis elegans, and genomic information about other
      nematodes and parasitic flatworms. Recent notable enhancements include user
      directed submission of data, such as micropublication; genomic data curation and
      presentation, including additional genomes and JBrowse, respectively; new query
      tools, such as SimpleMine, Gene Enrichment Analysis; new data displays, such as
      the Person Lineage browser and the Summary of Ontology-based Annotations.
      Anticipating more rapid data growth ahead, WormBase continues the process of
      migrating to a cutting-edge database technology to achieve better stability,
      scalability, reproducibility and a faster response time. To better serve the
      broader research community, WormBase, with five other Model Organism Databases
      and The Gene Ontology project, have begun to collaborate formally as the Alliance
      of Genome Resources.

PMID- 29069414
TI  - The BioStudies database-one stop shop for all data supporting a life sciences
      study.
AB  - BioStudies (www.ebi.ac.uk/biostudies) is a new public database that organizes
      data from biological studies. Typically, but not exclusively, a study is
      associated with a publication. BioStudies offers a simple way to describe the
      study structure, and provides flexible data deposition tools and data access
      interfaces. The actual data can be stored either in BioStudies or remotely, or
      both. BioStudies imports supplementary data from Europe PMC, and is a resource
      for authors and publishers for packaging data during the manuscript preparation
      process. It also can support data management needs of collaborative projects. The
      growth in multiomics experiments and other multi-faceted approaches to life
      sciences research mean that studies result in a diversity of data outputs in
      multiple locations. BioStudies presents a solution to ensuring that all these
      data and the associated publication(s) can be found coherently in the longer
      term.

PMID- 29069415
TI  - Serotype-Specific Correlates of Protection for Pneumococcal Carriage: An Analysis
      of Immunity in 19 Countries.
AB  - Background: Pneumococcal conjugate vaccines (PCVs) provide direct protection
      against disease in those vaccinated, and interrupt transmission through the
      prevention of nasopharyngeal (NP) carriage. Methods: We analyzed immunogenicity
      data from 5224 infants who received PCV in prime-boost schedules. We defined any
      increase in antibody between the 1-month postpriming visit and the booster dose
      as an indication of NP carriage ("seroincidence"). We calculated antibody
      concentrations using receiver operating characteristic curves, and used
      generalized additive models to compute their protective efficacy against
      seroincidence. To support seroincidence as a marker of carriage, we compared
      seroincidence in a randomized immunogenicity trial in Nepal with the serotype
      specific prevalence of carriage in the same community. Results: In Nepalese
      infants, seroincidence of carriage closely correlated with serotype-specific
      carriage prevalence in the community. In the larger data set, antibody
      concentrations associated with seroincidence were lowest for serotypes 6B and 23F
      (0.50 ug/mL and 0.63 ug/mL, respectively), and highest for serotypes 19F and 14
      (2.54 ug/mL and 2.48 ug/mL, respectively). The protective efficacy of antibody at
      these levels was 62% and 74% for serotypes 6B and 23F, and 87% and 84% for
      serotypes 19F and 14. Protective correlates were on average 2.15 times higher in
      low/lower middle-income countries than in high/upper middle-income countries
      (geometric mean ratio, 2.15 [95% confidence interval, 1.46-3.17]; P = .0024).
      Conclusions: Antibody concentrations associated with protection vary between
      serotypes. Higher antibody concentrations are required for protection in low
      income countries. These findings are important for global vaccination policy, to
      interrupt transmission by protecting against carriage.

PMID- 29069411
TI  - Distinct roles for the IIId2 sub-domain in pestivirus and picornavirus internal
      ribosome entry sites.
AB  - Viral internal ribosomes entry site (IRES) elements coordinate the recruitment of
      the host translation machinery to direct the initiation of viral protein
      synthesis. Within hepatitis C virus (HCV)-like IRES elements, the sub-domain
      IIId(1) is crucial for recruiting the 40S ribosomal subunit. However, some HCV
      like IRES elements possess an additional sub-domain, termed IIId2, whose function
      remains unclear. Herein, we show that IIId2 sub-domains from divergent viruses
      have different functions. The IIId2 sub-domain present in Seneca valley virus
      (SVV), a picornavirus, is dispensable for IRES activity, while the IIId2 sub
      domains of two pestiviruses, classical swine fever virus (CSFV) and border
      disease virus (BDV), are required for 80S ribosomes assembly and IRES activity.
      Unlike in SVV, the deletion of IIId2 from the CSFV and BDV IRES elements impairs
      initiation of translation by inhibiting the assembly of 80S ribosomes.
      Consequently, this negatively affects the replication of CSFV and BDV. Finally,
      we show that the SVV IIId2 sub-domain is required for efficient viral RNA
      synthesis and growth of SVV, but not for IRES function. This study sheds light on
      the molecular evolution of viruses by clearly demonstrating that conserved RNA
      structures, within distantly related RNA viruses, have acquired different roles
      in the virus life cycles.

PMID- 29069416
TI  - Importance of the positively charged residue at position 54 to the chaperoning
      function, conformational stability and amyloidogenic nature of human alphaA
      crystallin.
AB  - Arginine 54 (R54) in alphaA-Crystallin (alphaA-Cry) is highly conserved within
      different species. Recently, three missense mutations at this hot spot position
      have been reported to cause congenital cataract disorders. To investigate the
      impact of charge on structural and functional aspects of alphaA-Cry, R54 was
      individually substituted with lysine and aspartate. Replacement of R54 with the
      positively and negatively charged residues led to structural alteration and
      reduction in the protein conformational and proteolytic stability. Also, these
      mutations resulted in important increase in the amyloidogenic propensity of
      alphaA-Cry. Additionally, all these changes were more pronounced upon R54D
      mutation. Keeping the positive charge by R54K mutation, the structural integrity
      and stability of alphaA-Cry were partially preserved. Our results suggest that
      arginine 54 may also participate in salt bridge formation and conformational
      stabilization of alphaA-Cry. Also, it seems that unique physicochemical
      properties of arginine 54 may have a prominent role in the structural integrity,
      conformational stability and functional aspects of human alphaA-Cry.

PMID- 29069417
TI  - Conformational profiling of a G-rich sequence within the c-KIT promoter.
AB  - G-quadruplexes (G4) within oncogene promoters are considered to be promising
      anticancer targets. However, often they undergo complex structural rearrangements
      that preclude a precise description of the optimal target. Moreover, even when
      solved structures are available, they refer to the thermodynamically stable forms
      but little or no information is supplied about their complex multistep folding
      pathway. To shed light on this issue, we systematically followed the kinetic
      behavior of a G-rich sequence located within the c-KIT proximal promoter (kit2)
      in the presence of monovalent cations K+ and Na+. A very short-lived intermediate
      was observed to start the G4 folding process in both salt conditions.
      Subsequently, the two pathways diverge to produce distinct thermodynamically
      stable species (parallel and antiparallel G-quadruplex in K+ and Na+,
      respectively). Remarkably, in K+-containing solution a branched pathway is
      required to drive the wild type sequence to distribute between a monomeric and
      dimeric G-quadruplex. Our approach has allowed us to identify transient forms
      whose relative abundance is regulated by the environment; some of them were
      characterized by a half-life within the timescale of physiological DNA processing
      events and thus may represent possible unexpected targets for ligands
      recognition.

PMID- 29069418
TI  - Recruitment and establishment of the gut microbiome in arctic shorebirds.
AB  - Gut microbiota play a key role in host health. Mammals acquire gut microbiota
      during birth, but timing of gut microbial recruitment in birds is unknown. We
      evaluated whether precocial chicks from three species of arctic-breeding
      shorebirds acquire gut microbiota before or after hatching, and then documented
      the rate and compositional dynamics of accumulation of gut microbiota. Contrary
      to earlier reports of microbial recruitment before hatching in chickens,
      quantitative PCR and Illumina sequence data indicated negligible microbiota in
      the guts of shorebird embryos before hatching. Analyses of chick feces indicated
      an exponential increase in bacterial abundance of guts 0-2 days post-hatch,
      followed by stabilization. Gut communities were characterized by stochastic
      recruitment and convergence towards a community dominated by Clostridia and
      Gammaproteobacteria. We conclude that guts of shorebird chicks are likely void of
      microbiota prior to hatch, but that stable gut microbiome establishes as early as
      3 days of age, probably from environmental inocula.

PMID- 29069419
TI  - Prediction of contrast induced acute kidney injury using novel biomarkers
      following contrast coronary angiography.
AB  - Background/Introduction: Chronic kidney disease (CKD) is a risk factor for
      contrast induced acute kidney injury (CI-AKI). Contrast angiography in CKD
      patients is a common procedure. Creatinine is a delayed marker of CI-AKI and
      delays diagnosis which results in significant morbidity and mortality. Aim: Early
      diagnosis of CI-AKI requires validated novel biomarkers. Design: A prospective
      observation study of 301 consecutive CKD patients undergoing coronary angiography
      was performed. Methods: Samples for plasma neutrophil gelatinase-associated
      lipocalin (NGAL), serum liver fatty acid-binding protein (L-FABP), serum kidney
      injury marker 1, serum interleukin 18 and serum creatinine were taken at 0, 1, 2,
      4, 6 and 48 h post-contrast. Urinary NGAL and urinary cystatin C were collected
      at 0, 6 and 48 h. Incidence of major adverse clinical events (MACE) was recorded
      at 1 year. CI-AKI was defined as an absolute delta rise in creatinine of >=26.5
      umol/l or a 50% relative rise from baseline at 48 h following contrast. Results:
      CI-AKI occurred in 28 (9.3%) patients. Plasma NGAL was most predictive of CI-AKI
      at 6 h. L-FABP performed best at 4 h. A combination of Mehran score > 10, 4 h L
      FABP and 6 h NGAL improved specificity to 96.7%. MACE was statistically higher at
      1 year in CI-AKI patients (25.0 vs. 6.2% in non-CI-AKI patients).
      Discussion/Conclusion: Mehran risk score, 4 h serum L-FAPB and 6 h plasma NGAL
      performed best at early CI-AKI prediction. CI-AKI patients were four times more
      likely to develop MACE and had a trebling of mortality risk at 1 year.

PMID- 29069420
TI  - Fecal bacterial communities of wild-captured and stranded green turtles (Chelonia
      mydas) on the Great Barrier Reef.
AB  - Green turtles (Chelonia mydas) are endangered marine herbivores that break down
      food particles, primarily sea grasses, through microbial fermentation. However,
      the microbial community and its role in health and disease is still largely
      unexplored. In this study, we investigated and compared the fecal bacterial
      communities of eight wild-captured green turtles to four stranded turtles in the
      central Great Barrier Reef regions that include Bowen and Townsville. We used
      high-throughput sequencing analysis targeting the hypervariable V1-V3 regions of
      the bacterial 16S rRNA gene. At the phylum level, Firmicutes predominated among
      wild-captured green turtles, followed by Bacteroidetes and Proteobacteria. In
      contrast, Proteobacteria (Gammaproteobacteria) was the most significantly
      dominant phylum among all stranded turtles, followed by Bacteroidetes and
      Firmicutes. In addition, Fusobacteria was also significantly abundant in stranded
      turtles. No significant differences were found between the wild-captured turtles
      in Bowen and Townsville. At the family level, the core bacterial community
      consisted of 25 families that were identified in both the wild-captured and
      stranded green turtles, while two unique sets of 14 families each were only found
      in stranded or wild-captured turtles. The predominance of Bacteroides in all
      groups indicates the importance of these bacteria in turtle gut health. In terms
      of bacterial diversity and richness, wild-captured green turtles showed a higher
      bacterial diversity and richness compared with stranded turtles. The marked
      differences in the bacterial communities between wild-captured and stranded
      turtles suggest the possible dysbiosis in stranded turtles in addition to
      potential causal agents.

PMID- 29069421
TI  - Comparative efficacy and safety of treatment options for MDR and XDR
      Acinetobacter baumannii infections: a systematic review and network meta
      analysis.
AB  - Objectives: To comprehensively compare and rank the efficacy and safety of
      available treatment options for patients with MDR and XDR Acinetobacter baumannii
      (AB) infection. Methods: We searched PubMed, Embase and the Cochrane register of
      trials systematically for studies that examined treatment options for patients
      with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was
      performed to estimate the risk ratio (RR) and 95% CI from both direct and
      indirect evidence. Primary outcomes were clinical cure and microbiological cure.
      Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic
      adverse events. Results: A total of 29 studies with 2529 patients (median age 60
      years; 65% male; median APACHE II score 19.0) were included. Although there were
      no statistically significant differences between treatment options, triple
      therapy with colistin, sulbactam and tigecycline had the highest clinical cure
      rate. Colistin in combination with sulbactam was associated with a significantly
      higher microbiological cure rate compared with colistin in combination with
      tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI
      1.06-1.38). No significant differences in all-cause mortality were noted between
      treatment options. Tigecycline-based therapy also appeared less effective for
      achieving a microbiological cure and is not appropriate for treating bloodstream
      MDR- and XDR-AB infections. Conclusions: Combination therapy of colistin with
      sulbactam demonstrates superiority in terms of microbiological cure with a safety
      profile similar to that of colistin monotherapy. Thus, our findings support the
      use of this combination as a treatment for MDR- and XDR-AB infections.

PMID- 29069422
TI  - A Noninvasive Rhizopus Infection With a Bladder Fungal Ball in a Patient With
      Poorly Controlled Diabetes Mellitus.
AB  - Here we present the first reported case of a noninvasive Rhizopus fungal ball
      confined to the bladder of a patient with poorly controlled diabetes and right
      flank pain. The patient developed bilateral hydronephrosis after several hospital
      admissions for urinary tract infections with multiple failed courses of
      antibiotics. During cystoscopy to replace a ureteral stent, he was found to
      harbor a fungal ball in the bladder that was removed and grew Rhizopus in
      culture. Patient received treatment with amphotericin B and transitioned to long
      term posaconazole therapy. This case highlights the importance of considering
      fungal agents in urinary tract infections, especially in persistent or refractory
      cases, and the role of the clinical microbiology laboratory in correct
      identification of the infectious source.

PMID- 29069423
TI  - Testosterone and Corticosterone in the Mesocorticolimbic System of Male Rats:
      Effects of Gonadectomy and Caloric Restriction.
AB  - Steroid hormones can modulate motivated behaviors through the mesocorticolimbic
      system. Gonadectomy (GDX) is a common method to determine how steroids influence
      the mesocorticolimbic system, and caloric restriction (CR) is often used to
      invigorate motivated behaviors. A common assumption is that the effects of these
      manipulations on brain steroid levels reflects circulating steroid levels. We now
      know that the brain regulates local steroid levels in a region-specific manner;
      however, previous studies have low spatial resolution. Using ultrasensitive
      liquid chromatography tandem mass spectrometry, we examined steroids in
      microdissected regions of the mesocorticolimbic system (ventral tegmental area,
      nucleus accumbens, medial prefrontal cortex). We examined whether GDX or CR
      influences systemic and local steroids, particularly testosterone (T) and
      steroidogenic enzyme transcripts. Adult male rats underwent a GDX surgery and/or
      CR for either 2 or 6 weeks. Levels of T, the primary steroid of interest, were
      higher in all brain regions than in the blood, whereas corticosterone (CORT) was
      lower in the brain than in the blood. Importantly, GDX completely eliminated T in
      the blood and lowered T in the brain. Yet, T remained present in the brain, even
      6 weeks after GDX. CR decreased both T and CORT in the blood and brain.
      Steroidogenic enzyme (Cyp17a1, 3beta-hydroxysteroid dehydrogenase, aromatase)
      transcripts and androgen receptor transcripts were expressed in the
      mesocorticolimbic system and differentially affected by GDX and CR. Together,
      these results suggest that T is synthesized within the mesocorticolimbic system.
      These results provide a foundation for future studies examining how neurosteroids
      influence behaviors mediated by the mesocorticolimbic system.

PMID- 29069424
TI  - Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR
      project funded by the Health Care Quality Improvement Partnership.
AB  - Objective: Timely access to holistic multidisciplinary care is the core principle
      underpinning management of juvenile idiopathic arthritis (JIA). Data collected in
      national clinical audit programmes fundamentally aim to improve health outcomes
      of disease, ensuring clinical care is equitable, safe and patient-centred. The
      aim of this study was to develop a tool for national audit of JIA in the UK.
      Methods: A staged and consultative methodology was used across a broad group of
      relevant stakeholders to develop a national audit tool, with reference to pre
      existing standards of care for JIA. The tool comprises key service delivery
      quality measures assessed against two aspects of impact, namely disease-related
      outcome measures and patient/carer reported outcome and experience measures.
      Results: Eleven service-related quality measures were identified, including those
      that map to current standards for commissioning of JIA clinical services in the
      UK. The three-variable Juvenile Arthritis Disease Activity Score and
      presence/absence of sacro-iliitis in patients with enthesitis-related arthritis
      were identified as the primary disease-related outcome measures, with
      presence/absence of uveitis a secondary outcome. Novel patient/carer reported
      outcomes and patient/carer reported experience measures were developed and face
      validity confirmed by relevant patient/carer groups. Conclusion: A tool for
      national audit of JIA has been developed with the aim of benchmarking current
      clinical practice and setting future standards and targets for improvement.
      Staged implementation of this national audit tool should facilitate investigation
      of variability in levels of care and drive quality improvement. This will require
      engagement from patients and carers, clinical teams and commissioners of JIA
      services.

PMID- 29069425
TI  - Recall of Point-of-Sale Marketing Predicts Cigar and E-Cigarette Use Among Texas
      Youth.
AB  - Introduction: While research has documented associations between recall of point
      of-sale (POS) tobacco marketing and youth tobacco use, much of the research is
      cross-sectional and focused on cigarettes. The present longitudinal study
      examined recall of tobacco marketing at the POS and multiple types of tobacco use
      6 months later. Methods: The Texas Adolescent Tobacco Advertising and Marketing
      Surveillance System (TATAMS) is a large-scale, representative study of 6th, 8th,
      and 10th graders in 79 middle and high schools in five counties in Texas.
      Weighted logistic regression examined associations between recall of tobacco
      advertisements and products on display at baseline and ever use, current use, and
      susceptibility to use for cigarette, e-cigarette, cigar, and smokeless products 6
      months later. Results: Students' recall of signs marketing e-cigarettes at
      baseline predicted ever e-cigarette use and increased susceptibility to use e
      cigarettes at follow-up, across all store types. Recall of e-cigarette displays
      only predicted susceptibility to use e-cigarettes at follow-up, across all store
      types. Both recall of signs marketing cigars and cigar product displays predicted
      current and ever cigar smoking and increased susceptibility to smoking cigars at
      follow-up, across all store types. Recall of cigarette and smokeless product
      marketing and displays was not associated with tobacco use measures. Conclusion:
      The POS environment continues to be an important influence on youth tobacco use.
      Restrictions on POS marketing, particularly around schools, are warranted.
      Implications: Cross-sectional studies have shown that exposure to POS cigarette
      marketing is associated with use of cigarettes among youth, though longitudinal
      evidence of the same is sparse and mixed. Cross-sectional studies have found that
      recall of cigars, smokeless product, and e-cigarette tobacco marketing at POS is
      associated with curiosity about tobacco use or intentions to use tobacco among
      youth, but limited longitudinal research has been conducted. Findings from the
      present longitudinal study suggest that recall of tobacco marketing at retail POS
      predicts ever use of e-cigarettes and cigars, current use of cigars, and
      susceptibility to cigar and e-cigarette use among youth.

PMID- 29069426
TI  - Small RNA-mediated Cry toxin silencing allows Bacillus thuringiensis to evade
      Caenorhabditis elegans avoidance behavioral defenses.
AB  - Pathogen avoidance behavior protects animal hosts against microbial pathogens.
      Pathogens have evolved specific strategies during coevolution in response to such
      host defenses. However, these strategies for combatting host avoidance behavioral
      defenses remain poorly understood. Here, we used Caenorhabditis elegans and its
      bacterial pathogen Bacillus thuringiensis as a model and determined that small
      RNA (sRNA)-mediated Cry toxin silencing allowed pathogens to evade host avoidance
      behavioral defenses. The B. thuringiensis strain YBT-1518, which encodes three
      nematicidal cry genes, is highly toxic to C. elegans. However, the expression of
      the most potent toxin, Cry5Ba, was silenced in this strain when YBT-1518 was
      outside the host. Cry5Ba silencing was due to the sRNA BtsR1, which bound to the
      RBS site of the cry5Ba transcript via direct base pairing and inhibited Cry5Ba
      expression. Upon ingestion by C. elegans, Cry5Ba was expressed in vivo by strain
      YBT-1518. Cry5Ba silencing may allow B. thuringiensis to avoid nematode
      behavioral defenses and then express toxins once ingested to kill the host and
      gain a survival advantage. Our work describes a novel model of sRNA-mediated
      regulation to aid pathogens in combating host avoidance behavioral defenses.

PMID- 29069427
TI  - Use of genetic and chemical synthetic lethality as probes of complexity in
      bacterial cell systems.
AB  - Different conditions and genomic contexts are known to have an impact on gene
      essentiality and interactions. Synthetic lethal interactions occur when a
      combination of perturbations, either genetic or chemical, result in a more
      profound fitness defect than expected based on the effect of each perturbation
      alone. Synthetic lethality in bacterial systems has long been studied; however,
      during the past decade, the emerging fields of genomics and chemical genomics
      have led to an increase in the scale and throughput of these studies. Here, we
      review the concepts of genomics and chemical genomics in the context of synthetic
      lethality and their revolutionary roles in uncovering novel biology such as the
      characterization of genes of unknown function and in antibacterial drug
      discovery. We provide an overview of the methodologies, examples and challenges
      of both genetic and chemical synthetic lethal screening platforms. Finally, we
      discuss how to apply genetic and chemical synthetic lethal approaches to
      rationalize the synergies of drugs, screen for new and improved antibacterial
      therapies and predict drug mechanism of action.

PMID- 29069428
TI  - Gelsolin pathogenic Gly167Arg mutation promotes domain-swap dimerization of the
      protein.
AB  - AGel amyloidosis is a genetic degenerative disease characterized by the
      deposition of insoluble gelsolin protein aggregates in different tissues. Until
      recently, this disease was associated with two mutations of a single residue
      (Asp187 to Asn/Tyr) in the second domain of the protein. The general opinion is
      that pathogenic variants are not per se amyloidogenic but rather that the
      mutations trigger an aberrant proteolytic cascade, which results in the
      production of aggregation prone fragments. Here, we report the crystal structure
      of the second domain of gelsolin carrying the recently identified Gly167Arg
      mutation. This mutant dimerizes through a three-dimensional domain swapping
      mechanism, forming a tight but flexible assembly, which retains the structural
      topology of the monomer. To date, such dramatic conformational changes of this
      type have not been observed. Structural and biophysical characterizations reveal
      that the Gly167Arg mutation alone is responsible for the monomer to dimer
      transition and that, even in the context of the full-length protein, the
      pathogenic variant is prone to form dimers. These data suggest that, in addition
      to the well-known proteolytic-dependent mechanism, an alternative oligomerization
      pathway may participate in gelsolin misfolding and aggregation. We propose to
      integrate this alternative pathway into the current model of the disease that may
      also be relevant for other types of AGel amyloidosis, and other related diseases
      with similar underlying pathological mechanisms.

PMID- 29069430
TI  - Exocyst and autophagy-related membrane trafficking in plants.
AB  - Endomembrane traffic in eukaryotic cells functions partially as a means of
      communication; delivery of membrane in one direction has to be balanced with a
      reduction at the other end. This effect is typically the case during the defence
      against pathogens. To combat pathogens, cellular growth and differentiation are
      suppressed, while endomembrane traffic is poised towards limiting the pathogen
      attack. The octameric exocyst vesicle-tethering complex was originally discovered
      as a factor facilitating vesicle-targeting and vesicle-plasma membrane (PM)
      fusion during exocytosis prior to and possibly during SNARE complex formation.
      Interestingly, it was recently implicated both in animals and plants in autophagy
      membrane traffic. In animal cells, the exocyst is integrated into the mTOR
      regulated energy metabolism stress/starvation pathway, participating in the
      formation and especially initiation of an autophagosome. In plants, the first
      functional link was to autophagy-related anthocyanin import to the vacuole and to
      starvation. In this concise review, we summarize the current knowledge of exocyst
      functions in autophagy and defence in plants that might involve unconventional
      secretion and compare it with animal conditions. Formation of different exocyst
      complexes during undisturbed cell growth, as opposed to periods of cellular
      stress reactions involving autophagy, might contribute to the coordination of
      endomembrane trafficking pathways.

PMID- 29069429
TI  - Effects of Beneficial Mutations in pykF Gene Vary over Time and across Replicate
      Populations in a Long-Term Experiment with Bacteria.
AB  - The fitness effects of mutations can depend on the genetic backgrounds in which
      they occur and thereby influence future opportunities for evolving populations.
      In particular, mutations that fix in a population might change the selective
      benefit of subsequent mutations, giving rise to historical contingency. We
      examine these effects by focusing on mutations in a key metabolic gene, pykF,
      that arose independently early in the history of 12 Escherichia coli populations
      during a long-term evolution experiment. Eight different evolved nonsynonymous
      mutations conferred similar fitness benefits of ~10% when transferred into the
      ancestor, and these benefits were greater than the one conferred by a deletion
      mutation. In contrast, the same mutations had highly variable fitness effects,
      ranging from ~0% to 25%, in evolved clones isolated from the populations at
      20,000 generations. Two mutations that were moved into these evolved clones
      conferred similar fitness effects in a given clone, but different effects between
      the clones, indicating epistatic interactions between the evolved pykF alleles
      and the other mutations that had accumulated in each evolved clone. We also
      measured the fitness effects of six evolved pykF alleles in the same populations
      in which they had fixed, but at seven time points between 0 and 50,000
      generations. Variation in fitness effects was high at intermediate time points,
      and declined to a low level at 50,000 generations, when the mean fitness effect
      was lowest. Our results demonstrate the importance of genetic context in
      determining the fitness effects of different beneficial mutations even within the
      same gene.

PMID- 29069431
TI  - Targeted antibody therapy and relevant novel biomarkers for precision medicine
      for rheumatoid arthritis.
AB  - Over the past two decades, the management of rheumatoid arthritis (RA) has
      progressed remarkably, encompassing the development of new diagnostic tools and
      efficacious biological agents, such as monoclonal antibodies against inflammatory
      cytokines and surface markers on immune cells. In addition to the significant
      efficacy of these biological agents, biomarkers for RA are under consideration
      for their potential to classify heterogeneous patients into several groups based
      on clinical and immunological phenotypes for the prediction of clinical course
      and prognosis and the facilitation of appropriate and precise treatment with the
      appropriate therapeutic monoclonal antibodies. Biomarkers, particularly those for
      the prediction and monitoring of the responses to therapeutic monoclonal
      antibodies for RA, are in demand, with many approaches examined in recent years.
      In this article, we have summarized the background research on biomarkers and
      introduced recent topics in the field that enable the possible clinical
      applications of biomarkers, especially those related to pathogenic cytokines, to
      guide the treatment of RA.

PMID- 29069432
TI  - SUMO E3 Ligase SlSIZ1 Facilitates Heat Tolerance in Tomato.
AB  - High temperature has become a major abiotic stress that limits crop productivity.
      Heat shock transcription factors (HSFs) and heat shock proteins (HSPs) play
      important roles in enhancing thermotolerance of plants. SUMOylation is an
      important post-translational modification in regulating cellular functions in
      eukaryotes. SIZ1, a well-characterized SUMO E3 ligase, mediates the process of
      SUMOylation. In this study, SUMO conjugations were clearly induced by high
      temperature. Overexpression of SIZ1 SUMO E3 ligase (SlSIZ1) in tomato could
      enhance the tolerance to heat stress in tomato. The RNA interference (RNAi)
      plants were more wilted than the wild type with heat treatment. Under heat
      stress, SlSIZ1 could decrease the accumulation of reactive oxygen species (ROS)
      and induce some genes of HSF and HSP transcription. Furthermore, overexpression
      of SlSIZ1 could increase the level of Hsp70 under high temperature. Yeast two
      hybrid and bimolecular fluorescence complementation (BiFC) assays showed that
      SlSIZ1 could interact with SlHsfA1 to mediate the SUMOylation of SlHsfA1 and
      consequently enhance thermotolerance of tomato. In conclusion, overexpression of
      SlSIZ1 enhanced heat tolerance by regulating the activities of HsfA1 and
      increasing the content Hsp70.

PMID- 29069433
TI  - Modulation of extracytoplasmic function (ECF) sigma factor promoter selectivity
      by spacer region sequence.
AB  - The ability of bacteria to adapt to stress depends on the conditional expression
      of specific sets of genes. Bacillus subtilis encodes seven extracytoplasmic
      function (ECF) sigma (sigma) factors that regulate functions important for
      survival under conditions eliciting cell envelope stress. Of these, four have
      been studied in detail: sigmaM, sigmaW, sigmaX and sigmaV. These four sigma
      factors recognize overlapping sets of promoters, although the sequences that
      determine this overlapping recognition are incompletely understood. A major role
      in promoter selectivity has been ascribed to the core -10 and -35 promoter
      elements. Here, we demonstrate that a homopolymeric T-tract motif, proximal to
      the -35 element, functions in combination with the core promoter sequences to
      determine selectivity for ECF sigma factors. This motif is most critical for
      promoter activation by sigmaV, and contributes variably to activation by sigmaM,
      sigmaX and sigmaW. We propose that this motif, which is a feature of the deduced
      promoter consensus for a subset of ECF sigma factors from many species, imparts
      intrinsic DNA curvature to influence promoter activity. The differential effect
      of this region among ECF sigma factors thereby provides a mechanism to modulate
      the nature and extent of regulon overlap.

PMID- 29069434
TI  - Estimating Age-Dependent Extinction: Contrasting Evidence from Fossils and
      Phylogenies.
AB  - The estimation of diversification rates is one of the most vividly debated topics
      in modern systematics, with considerable controversy surrounding the power of
      phylogenetic and fossil-based approaches in estimating extinction. Van Valen's
      seminal work from 1973 proposed the "Law of constant extinction," which states
      that the probability of extinction of taxa is not dependent on their age. This
      assumption of age-independent extinction has prevailed for decades with its
      assessment based on survivorship curves, which, however, do not directly account
      for the incompleteness of the fossil record, and have rarely been applied at the
      species level. Here, we present a Bayesian framework to estimate extinction rates
      from the fossil record accounting for age-dependent extinction (ADE). Our
      approach, unlike previous implementations, explicitly models unobserved species
      and accounts for the effects of fossil preservation on the observed longevity of
      sampled lineages. We assess the performance and robustness of our method through
      extensive simulations and apply it to a fossil data set of terrestrial Carnivora
      spanning the past 40 myr. We find strong evidence of ADE, as we detect the
      extinction rate to be highest in young species and declining with increasing
      species age. For comparison, we apply a recently developed analogous ADE model to
      a dated phylogeny of extant Carnivora. Although the phylogeny-based analysis also
      infers ADE, it indicates that the extinction rate, instead, increases with
      increasing taxon age. The estimated mean species longevity also differs
      substantially, with the fossil-based analyses estimating 2.0 myr, in contrast to
      9.8 myr derived from the phylogeny-based inference. Scrutinizing these
      discrepancies, we find that both fossil and phylogeny-based ADE models are prone
      to high error rates when speciation and extinction rates increase or decrease
      through time. However, analyses of simulated and empirical data show that fossil
      based inferences are more robust. This study shows that an accurate estimation of
      ADE from incomplete fossil data is possible when the effects of preservation are
      jointly modeled, thus allowing for a reassessment of Van Valen's model as a
      general rule in macroevolution.

PMID- 29069435
TI  - Auditory Verbal Hallucinations in Schizophrenia From a Levels of Explanation
      Perspective.
AB  - In the present article, we present a "Levels of Explanation" (LoE) approach to
      auditory verbal hallucinations (AVHs) in schizophrenia. Mental phenomena can be
      understood at different levels of explanation, including cultural, clinical,
      cognitive, brain imaging, cellular, and molecular levels. Current research on
      AVHs is characterized by accumulation of data at all levels, but with little or
      no interaction of findings between levels. A second advantage with a Levels of
      Explanation approach is that it fosters interdisciplinarity and collaboration
      across traditional borders, facilitating a real breakthrough in future research.
      We exemplify a Levels of Explanation approach with data from 3 levels where
      findings at 1 level provide predictions for another level. More specifically, we
      show how functional neuroimaging data at the brain level correspond with
      behavioral data at the cognitive level, and how data at these 2 levels correspond
      with recent findings of changes in neurotransmitter function at the cellular
      level. We further discuss implications for new therapeutic interventions, and the
      article is ended by suggestion how future research could incorporate genetic
      influences on AVHs at the molecular level of explanation by providing examples
      for animal work.

PMID- 29069437
TI  - AT THE PHYSICS-BIOLOGY INTERFACE: THE NEUTRON AFFAIR.
AB  - We present predictions of neutron relative biological effectiveness (RBE) for
      cell irradiations with neutron beams at PTB-Braunschweig. A neutron RBE model is
      adopted to evaluate initial DNA damage induction given the neutron-induced
      charged particle field. RBE values are predicted for cell exposures to quasi
      monoenergetic beams (0.56 MeV, 1.2 MeV) and to a broad energy distribution
      neutron field with dose-averaged energy of 5.75 MeV. Results are compared to what
      obtained with our RBE predictions for neutrons at similar energies, when a 30-cm
      sphere is irradiated in an isotropic neutron field. RBE values for experimental
      conditions are higher for the lowest neutron energies, because, as expected,
      target geometry determines the weight of the low-effectiveness photon component
      of the neutron dose. These results highlight the importance of characterizing
      neutron fields in terms of physical interactions, to fully understand neutron
      induced biological effects, contributing to risk estimation and to the
      improvement of radiation protection standards.

PMID- 29069439
TI  - From the Cover: 2.45-GHz Microwave Radiation Impairs Hippocampal Learning and
      Spatial Memory: Involvement of Local Stress Mechanism-Induced Suppression of
      iGluR/ERK/CREB Signaling.
AB  - Microwave (MW) radiation induced oxidative stress reduces dendritic arborization,
      spine density and number of hippocampal pyramidal neurons and hence, impair
      learning and spatial memory through p53-dependent/independent apoptosis of
      hippocampal neuronal and nonneuronal cells. However, the mechanisms responsible
      for MW radiation induced impairment in memory formation remains still unknown.
      This study elucidates the effect of short (15 days) and long-term (30 and 60
      days) low level 2.45 GHz MW radiation-induced local stress on the hippocampal
      spatial memory formation pathway in adult male mice. Twelve-weeks old mice were
      exposed to 2.45 GHz MW radiation (continuous-wave with overall average Power
      density of 0.0248 mW/cm2 and overall average whole body SAR value of 0.0146 W/Kg)
      @ 2 h/d for 15, 30, and 60 days. Learning and spatial memory was assessed by 8
      arm radial maze. We have investigated the alterations in serum corticosterone
      level and the expression of glucocorticoid receptor, corticotropin-releasing
      hormone (CRH), inducible nitric oxide synthase (i-NOS), iGluRs, PSD-95-neuronal
      NOS (n-NOS) system, protein kinase A, protein kinase Cepsilon-ERK1/2-pERK1/2 in
      all the hippocampal subregions, viz. CA1, CA2, CA3, and DG through
      immunohistochemistry/immunofluorescence and alterations in the expression of
      hippocampal glucocorticoid receptor, CRH-receptor 1 (CRH-R1), cAMP-response
      element-binding (CREB), and phosphorylated-CREB (p-CREB) through western blot
      analysis. We observed that 2.45 GHz MW irradiated mice showed slow learning and
      significantly increased number of working and reference memory errors in radial
      maze task. Further, 2.45 GHz MW radiation exposure increases serum corticosterone
      level and the expression of CRH, CRH-R1, and i-NOS, while the expression of
      iGluRs, n-NOS, PSD-95, protein kinase Cepsilon, protein kinase A, ERK-p-ERK,
      CREB, and p-CREB decreases in above mentioned hippocampal subregions in a
      duration dependent manner. Our findings led us to conclude that 2.45 GHz MW
      radiation exposure induced local stress suppresses signaling mechanism(s) of
      hippocampal memory formation.

PMID- 29069436
TI  - Structural Brain Abnormalities in Successfully Treated HIV Infection:
      Associations With Disease and Cerebrospinal Fluid Biomarkers.
AB  - Background: Brain structural abnormalities have been reported in persons living
      with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive
      combination antiretroviral therapy (cART), but their pathophysiology remains
      unclear. Methods: We investigated factors associated with brain tissue volumes
      and white matter microstructure (fractional anisotropy) in 134 PLWH receiving
      suppressive cART and 79 comparable HIV-negative controls, aged >=45 years, from
      the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and
      cerebrospinal fluid biomarkers. Results: Compared with controls, PLWH had lower
      gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and
      fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with
      the largest differences observed in those with prior clinical AIDS. Hypertension
      and the soluble CD14 concentration in cerebrospinal fluid were associated with
      lower fractional anisotropy. These associations were independent of HIV
      serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not
      explain the greater abnormalities in brain structure in relation to HIV
      infection. Conclusions: The presence of lower gray matter volumes and more white
      matter microstructural abnormalities in well-treated PLWH partly reflect a
      combination of historical effects of AIDS, as well as the more general influence
      of systemic factors, such as hypertension and ongoing neuroinflammation.
      Additional mechanisms explaining the accentuation of brain structure
      abnormalities in treated HIV infection remain to be identified.

PMID- 29069438
TI  - Loss of heparan sulfate in the niche leads to tumor-like germ cell growth in the
      Drosophila testis.
AB  - The stem cell niche normally prevents aberrant stem cell behaviors that lead to
      cancer formation. Recent studies suggest that some cancers are derived from
      endogenous populations of adult stem cells that have somehow escaped from normal
      control by the niche. However, the molecular mechanisms by which the niche
      retains stem cells locally and tightly controls their divisions are poorly
      understood. Here, we demonstrate that the presence of heparan sulfate (HS), a
      class glygosaminoglycan chains, in the Drosophila germline stem cell niche
      prevents tumor formation in the testis. Loss of HS in the niche, called the hub,
      led to gross changes in the morphology of testes as well as the formation of both
      somatic and germline tumors. This loss of hub HS resulted in ectopic signaling
      events in the Jak/Stat pathway outside the niche. This ectopic Jak/Stat signaling
      disrupted normal somatic cell differentiation, leading to the formation of
      tumors. Our finding indicates a novel non-autonomous role for niche HS in
      ensuring the integrity of the niche and preventing tumor formation.

PMID- 29069440
TI  - Tight interaction of eEF2 in the presence of Stm1 on ribosome.
AB  - The stress-related protein Stm1 interacts with ribosomes, and is implicated in
      repressing translation. Stm1 was previously studied both in vivo and in vitro by
      cell-free translation systems using crude yeast lysates, but its precise
      functional mechanism remains obscure. Using an in vitro reconstituted translation
      system, we now show that Stm1 severely inhibits translation through its N
      terminal region, aa 1 to 107, and this inhibition is antagonized by eEF3. We
      found that Stm1 stabilizes eEF2 on the 80 S ribosome in the GTP-bound form,
      independently of eEF2's diphthamide modification, a conserved post-translational
      modification at the tip of domain IV. Systematic analyses of N- or C-terminal
      truncated mutants revealed that the core region of Stm1, aa 47 to 143, is crucial
      for its ribosome binding and eEF2 stabilization. Stm1 does not inhibit the 80 S
      dependent GTPase activity of eEF2, at least during the first round of GTP
      hydrolysis. The mechanism and the role of the stable association of eEF2 with the
      ribosome in the presence of Stm1 are discussed in relation to the translation
      repression by Stm1.

PMID- 29069441
TI  - PolyA_DB 3 catalogs cleavage and polyadenylation sites identified by deep
      sequencing in multiple genomes.
AB  - PolyA_DB is a database cataloging cleavage and polyadenylation sites (PASs) in
      several genomes. Previous versions were based mainly on expressed sequence tags
      (ESTs), which had a limited amount and could lead to inaccurate PAS
      identification due to the presence of internal A-rich sequences in transcripts.
      Here, we present an updated version of the database based solely on deep
      sequencing data. First, PASs are mapped by the 3' region extraction and deep
      sequencing (3'READS) method, ensuring unequivocal PAS identification. Second, a
      large volume of data based on diverse biological samples increases PAS coverage
      by 3.5-fold over the EST-based version and provides PAS usage information. Third,
      strand-specific RNA-seq data are used to extend annotated 3' ends of genes to
      obtain more thorough annotations of alternative polyadenylation (APA) sites.
      Fourth, conservation information of PAS across mammals sheds light on
      significance of APA sites. The database (URL: http://www.polya-db.org/v3)
      currently holds PASs in human, mouse, rat and chicken, and has links to the UCSC
      genome browser for further visualization and for integration with other genomic
      data.

PMID- 29069442
TI  - UV-based evaluation of ergosterol for monitoring the fungal exposure in Italian
      buffalo farms.
AB  - This study provided a reliable way to identify and estimate the ergosterol in
      farm environments, since it is renowned that it is a specific indicator for the
      occurrence of molds and yeasts. The quick valuation of exposure to airborne
      microorganisms is essential to assess the risk to which the health of employees
      is subjected in working places characterized by great humidity. From this view,
      it is worth estimating the total biomass of molds and yeast, including viable and
      non-viable forms, which may cause respiratory concerns to human. Air samples were
      collected with a passive method and the microbial growth was evaluated with a
      traditional counting method. At the same time, the ergosterol was quantified from
      yeasts and molds. In this way, the aerosol concentrations of molds and yeasts
      were compared by using the two methods, the cultivation on plates, as well as
      through ergosterol measurement by means of UV spectroscopy. Results showed, for
      the first time, a positive correlation between the amount of ergosterol and the
      yeast cells. Based on these outcomes, the ergosterol is a statistically
      significant biomarker to be used to control the air quality of indoor and outdoor
      farm spaces, by means of a simple and direct UV procedure.

PMID- 29069443
TI  - Structure of the large terminase from a hyperthermophilic virus reveals a unique
      mechanism for oligomerization and ATP hydrolysis.
AB  - The crystal structure of the large terminase from the Geobacillus
      stearothermophilus bacteriophage D6E shows a unique relative orientation of the N
      terminal adenosine triphosphatase (ATPase) and C-terminal nuclease domains. This
      monomeric 'initiation' state with the two domains 'locked' together is stabilized
      via a conserved C-terminal arm, which may interact with the portal protein during
      motor assembly, as predicted for several bacteriophages. Further work supports
      the formation of an active oligomeric state: (i) AUC data demonstrate the
      presence of oligomers; (ii) mutational analysis reveals a trans-arginine finger,
      R158, indispensable for ATP hydrolysis; (iii) the location of this arginine is
      conserved with the HerA/FtsK ATPase superfamily; (iv) a molecular docking model
      of the pentamer is compatible with the location of the identified arginine
      finger. However, this pentameric model is structurally incompatible with the
      monomeric 'initiation' state and is supported by the observed increase in kcat of
      ATP hydrolysis, from 7.8 +/- 0.1 min-1 to 457.7 +/- 9.2 min-1 upon removal of the
      C-terminal nuclease domain. Taken together, these structural, biophysical and
      biochemical data suggest a model where transition from the 'initiation' state
      into a catalytically competent pentameric state, is accompanied by substantial
      domain rearrangements, triggered by the removal of the C-terminal arm from the
      ATPase active site.

PMID- 29069444
TI  - Grain yield and quality responses of wheat expressing a barley sucrose
      transporter to combined climate change factors.
AB  - Crop yield stability must be ensured under future climate conditions such as
      elevated CO2 and high temperatures. We tested 'HOSUT', a winter wheat line
      expressing a grain-targeted sucrose transporter of barley in response to
      combinations of CO2 enrichment, a heat wave, and high nitrogen fertilization.
      Compared with wild-type Certo, HOSUT had a superior performance for grain yield,
      aboveground biomass, and ears per plant, obviously due to transgene activity in
      developing grains and young vegetative sinks. HOSUT grains were larger and
      contained more endosperm cells. HOSUT and high CO2 effects similarly improved
      phenological and yield-related traits. Significant HOSUT-CO2 interactions for
      biomass of stems, ears, grain yield, nitrogen yield, and grain number revealed
      that Certo was promoted by CO2 enrichment, whereas HOSUT responded weakly. CO2
      enrichment strongly reduced and HOSUT effects weakly reduced grain nitrogen,
      storage proteins, and free amino acids. In contrast to CO2 enrichment, HOSUT
      effects did not impair grain micronutrient concentrations. Significant HOSUT
      nitrogen fertilization interactions for ear biomass, grain yield, grain number
      per plant, and harvest index indicated that HOSUT benefited more from additional
      nitrogen. The heat wave decreased aboveground and ear biomass, grain yield,
      harvest index, grain size, and starch and water use, but increased grain sucrose
      concentration.

PMID- 29069445
TI  - TCSBN: a database of tissue and cancer specific biological networks.
AB  - Biological networks provide new opportunities for understanding the cellular
      biology in both health and disease states. We generated tissue specific
      integrated networks (INs) for liver, muscle and adipose tissues by integrating
      metabolic, regulatory and protein-protein interaction networks. We also generated
      human co-expression networks (CNs) for 46 normal tissues and 17 cancers to
      explore the functional relationships between genes as well as their relationships
      with biological functions, and investigate the overlap between functional and
      physical interactions provided by CNs and INs, respectively. These networks can
      be employed in the analysis of omics data, provide detailed insight into disease
      mechanisms by identifying the key biological components and eventually can be
      used in the development of efficient treatment strategies. Moreover, comparative
      analysis of the networks may allow for the identification of tissue-specific
      targets that can be used in the development of drugs with the minimum toxic
      effect to other human tissues. These context-specific INs and CNs are presented
      in an interactive website http://inetmodels.com without any limitation.

PMID- 29069446
TI  - 6,4-PP Photolyase Encoded by AtUVR3 is Localized in Nuclei, Chloroplasts and
      Mitochondria and its Expression is Down-Regulated by Light in a Photosynthesis
      Dependent Manner.
AB  - Pyrimidine dimers are the most important DNA lesions induced by UVB irradiation.
      They can be repaired directly by photoreactivation or indirectly by the excision
      repair pathways. Photoreactivation is carried out by photolyases, enzymes which
      bind to the dimers and use the energy of blue light or UVA to split bonds between
      adjacent pyrimidines. Arabidopsis thaliana has three known photolyases: AtPHR1,
      AtCRY3 and AtUVR3. Little is known about the cellular localization and regulation
      of AtUVR3 expression. We have found that its transcript level is down-regulated
      by light (red, blue or white) in a photosynthesis-dependent manner. The down
      regulatory effect of red light is absent in mature leaves of the phyB mutant, but
      present in leaves of phyAphyB. UVB irradiation does not increase AtUVR3
      expression in leaves. Transiently expressed AtUVR3-green fluorescent protein
      (GFP) is found in the nuclei, chloroplasts and mitochondria of Nicotiana
      benthamiana epidermal cells. In the nucleoplasm, AtUVR3-GFP is distributed
      uniformly, while in the nucleolus it forms speckles. Truncated AtUVR3 and muteins
      were used to identify the sequences responsible for its subcellular localization.
      Mitochondrial and chloroplast localization of AtUVR3 is independent of its N
      terminal sequence. Amino acids located at the C-terminal loop of the protein are
      involved in its transport into chloroplasts and its retention inside the
      nucleolus.

PMID- 29069447
TI  - The DifferentialNet database of differential protein-protein interactions in
      human tissues.
AB  - DifferentialNet is a novel database that provides users with differential
      interactome analysis of human tissues (http://netbio.bgu.ac.il/diffnet/). Users
      query DifferentialNet by protein, and retrieve its differential protein-protein
      interactions (PPIs) per tissue via an interactive graphical interface. To compute
      differential PPIs, we integrated available data of experimentally detected PPIs
      with RNA-sequencing profiles of tens of human tissues gathered by the Genotype
      Tissue Expression consortium (GTEx) and by the Human Protein Atlas (HPA). We
      associated each PPI with a score that reflects whether its corresponding genes
      were expressed similarly across tissues, or were up- or down-regulated in the
      selected tissue. By this, users can identify tissue-specific interactions, filter
      out PPIs that are relatively stable across tissues, and highlight PPIs that show
      relative changes across tissues. The differential PPIs can be used to identify
      tissue-specific processes and to decipher tissue-specific phenotypes. Moreover,
      they unravel processes that are tissue-wide yet tailored to the specific demands
      of each tissue.

PMID- 29069449
TI  - The MADS-Box Gene SlMBP21 Regulates Sepal Size Mediated by Ethylene and Auxin in
      Tomato.
AB  - Normal organ size is achieved by successful co-ordination of cell proliferation
      and cell expansion, which are modulated by multiple factors such as ethylene and
      auxin. In our work, SlMBP21-RNAi (RNA interference) tomato exhibited longer
      sepals and improved fruit set. Histological analysis indicated that longer sepals
      were attributed to cell expansion. To explore how SlMBP21 regulates sepal size,
      we compared the transcriptomes of sepals between SlMBP21-RNAi and the wild type
      by RNA sequencing and found that the differentially expressed genes were
      dominantly related to cell expansion, ethylene and auxin, and photosynthesis.
      Down-regulation of SlMBP21 affected ethylene production and the free IAA and IAA
      Val intensity in sepals. Hormone treatment further indicated that SlMBP21 was
      involved in the ethylene and auxin pathways. As reported, ethylene and auxin were
      important factors for cell expansion. Hence, SlMBP21 negatively regulated cell
      expansion to control sepal size, and ethylene and auxin may mediate this process.
      Additionally, the contents of Chl and the activity of ribulose-1, 5-bisphosphate
      carboxylase/oxygenase, the key photosynthetic enzyme, were both increased in
      SlMBP21-RNAi sepals, which indicated that photosynthesis might be enhanced in
      transgenic longer sepals. Therefore, the longer sepal, with better protection and
      enhanced photosynthesis, may contribute to improve fruit set. Altogether, these
      results suggested that SlMBP21 was a novel factor involved in organ size control.
      Moreover, our study provided potential application value for improving fruit set.

PMID- 29069448
TI  - Asymmetric cell division requires specific mechanisms for adjusting global
      transcription.
AB  - Most cells divide symmetrically into two approximately identical cells. There are
      many examples, however, of asymmetric cell division that can generate sibling
      cell size differences. Whereas physical asymmetric division mechanisms and cell
      fate consequences have been investigated, the specific problem caused by
      asymmetric division at the transcription level has not yet been addressed. In
      symmetrically dividing cells the nascent transcription rate increases in parallel
      to cell volume to compensate it by keeping the actual mRNA synthesis rate
      constant. This cannot apply to the yeast Saccharomyces cerevisiae, where this
      mechanism would provoke a never-ending increasing mRNA synthesis rate in smaller
      daughter cells. We show here that, contrarily to other eukaryotes with symmetric
      division, budding yeast keeps the nascent transcription rates of its RNA
      polymerases constant and increases mRNA stability. This control on RNA pol II
      dependent transcription rate is obtained by controlling the cellular
      concentration of this enzyme.

PMID- 29069450
TI  - Improvement of a yeast self-excising integrative vector by prevention of
      expression leakage of the intronated Cre recombinase gene during plasmid
      maintenance in Escherichia coli.
AB  - The use of plasmids possessing a regulatable gene coding for a site-specific
      recombinase together with its recognition sequences significantly facilitates
      genome manipulations since it allows self-excision of the portion of the genetic
      construct integrated into the host genome. Stable maintenance of such plasmids in
      Escherichia coli, which is used for plasmid preparation, requires prevention of
      recombinase synthesis in this host, which can be achieved by interrupting the
      recombinase gene with an intron. Based on this approach, Saccharomyces cerevisiae
      and Hansenula polymorpha self-excising vectors possessing intronated gene for Cre
      recombinase and its recognition sites (LoxP) were previously constructed.
      However, this work shows instability of the H. polymorpha vectors during plasmid
      maintenance in E. coli cells. This could be due to recombination between the loxP
      sites caused by residual expression of the cre gene. Prevention of translation
      reinitiation on an internal methionine codon completely solved this problem. A
      similar modification was made in a self-excising vector designed for S.
      cerevisiae. Apart from substantial improvement of yeast self-excising vectors,
      the obtained results also narrow down the essential part of Cre sequence.

PMID- 29069451
TI  - Poor recovery of households from out-of-pocket payment for assisted reproductive
      technology.
AB  - STUDY QUESTION: How do households recover financially from direct out-of-pocket
      payment for government subsidized ART? SUMMARY ANSWER: After a mean of 3.8 years,
      there was poor recovery from initiated financial coping strategies with the
      poorest households being disproportionatley affected. WHAT IS KNOWN ALREADY: Out
      of-pocket payment for health services can create financial burdens for households
      and inequities in access to care. A previous study conducted at a public-academic
      institution in South Africa documented that patient co-payment for one cycle of
      ART resulted in catastrophic expenditure for one in five households, and more
      frequently among the poorest, requiring diverse financial coping strategies to
      offset costs. STUDY DESIGN, SIZE, DURATION: An observational follow-up study was
      conducted ~4 years later to assess financial recovery among the 135 couples who
      had participated in this previous study. Data were collected over 12 months from
      73 informants. PARTICIPANTS/MATERIALS, SETTING, METHOD: The study was conducted
      at a level three referral hospital in the public-academic health sector of South
      Africa. At this institution ART is subsidized but requires patient co-payments. A
      purpose-built questionnaire capturing socio-economic information and recovery
      from financial coping strategies which had been activated was administered to all
      informants. Financial recovery was defined as the resolution of strategies
      initiated for the specific purpose of covering the original ART cycle. Results
      were analysed by strategy and household with the latter including analysis by
      tertiles based on socio-economic status at the time of the original expenditure.
      In addition to descriptive statistics, the Pearson Chi squared test was used to
      determine differences between socioeconomic tertiles and associations between
      recovery and other variables. MAIN RESULTS AND THE ROLE OF CHANCE: The
      participation rate in this follow-up study was 54.1% with equal representation
      from the three socio-economic tertiles. The average duration of follow-up was
      46.1 months (+/-9.78 SD) and respondents' mean age was 42 years (range 31-52).
      The recovery rate was below 50% for four of five strategies evaluated: 23.1% of
      households had re-purchased a sold asset; 23.5% had normalized a previous
      reduction in household spending, 33.8% had regained their savings, and 48.7% were
      no longer bolstering income through additional work. Two-thirds of households
      (60.0%) had repaid all loans and debts. The poorest households showed lower rates
      of recovery when compared to households in the richest tertile. Complete recovery
      from all strategies initiated was reported by only 10 households (13.7%): 1 of 19
      in the lowest tertile, 3 of 30 in the middle and by 6 of 24 households in the
      richest tertile (P > 0.05). No association was found between the degree of
      financial recovery and additional cost burdens incurred, including related to
      babies born; or between the degree of recovery and ongoing pursuit of ART.
      LIMITATIONS, REASONS FOR CAUTION: The sample size was limited. The participation
      rate was just over 50%. Results were dependent on participants' narrative and
      recall. WIDER IMPLICATIONS OF THE FINDINGS: The willingness of patients to pay
      for ART does not necessarily imply the ability to pay. As a result, the lack of
      comprehensive third-party funding for ART can create immediate and long-term
      financial hardship which is more pronounced among poorer households. While more
      data on the impact of out-of-pocket payment for ART are needed to illustrate the
      problem in other low resource settings, the results from South Africa provide
      useful information for similar developing countries. The current absence of more
      extensive data should therefore not be a barrier to the promotion of financial
      risk protection for infertile couples, especially the poorest, in need of ART.
      STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a Masters Student
      Grant from the Faculty of Health Sciences, University of Cape Town. The authors
      had no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

PMID- 29069453
TI  - Kinetic characterization of substrate-binding sites of thermostable tRNA
      methyltransferase (TrmB).
AB  - TrmB is a eubacterial tRNA methyltransferase which catalyzes the formation of N7
      methylguanosine at position 46 (m7G46) in tRNA consuming S-adenosyl-L-methionine
      (AdoMet) as the methyl group donor during the reaction. Previously, we purified
      TrmB from Aquifex aeolicus, a hyper-thermophilic eubacterium, and clarified the
      recognition sites in tRNA. Furthermore, we reported that an additional C-terminal
      region of A. aeolicus TrmB is required for protein stability at high
      temperatures. In the current study, we devised a new purification method to
      remove contaminating RNA completely. The purified enzyme is mainly in a monomeric
      form. We prepared 17 mutant A. aeolicus TrmB proteins and performed kinetic
      studies. Our analyses reveal that Glu47, Tyr95, Arg108, Thr165 and Tyr167
      residues are important for AdoMet binding and that Asp74, Asp97, and Thr132 are
      important for the methyltransfer reaction. Furthermore, substitution of Asp133 by
      alanine caused complete loss of enzymatic activity. Based on the results of our
      current studies and previous bioinformatic, biochemical and structural studies by
      others, a reaction mechanism for TrmB is proposed.

PMID- 29069452
TI  - Recombination Alters the Dynamics of Adaptation on Standing Variation in
      Laboratory Yeast Populations.
AB  - The rates and selective effects of beneficial mutations, together with population
      genetic factors such as population size and recombination rate, determine the
      outcomes of adaptation and the signatures this process leaves in patterns of
      genetic diversity. Previous experimental studies of microbial evolution have
      focused primarily on initially clonal populations, finding that adaptation is
      characterized by new strongly selected beneficial mutations that sweep rapidly to
      fixation. Here, we study evolution in diverse outcrossed yeast populations,
      tracking the rate and genetic basis of adaptation over time. We combine time
      serial measurements of fitness and allele frequency changes in 18 populations of
      budding yeast evolved at different outcrossing rates to infer the drivers of
      adaptation on standing genetic variation. In contrast to initially clonal
      populations, we find that adaptation is driven by a large number of weakly
      selected, linked variants. Populations undergoing different rates of outcrossing
      make use of this selected variation differently: whereas asexual populations
      evolve via rapid, inefficient, and highly variable fixation of clones, sexual
      populations adapt continuously by gradually breaking down linkage disequilibrium
      between selected variants. Our results demonstrate how recombination can sustain
      adaptation over long timescales by inducing a transition from selection on
      genotypes to selection on individual alleles, and show how pervasive linked
      selection can affect evolutionary dynamics.

PMID- 29069454
TI  - ghr-miR5272a-mediated regulation of GhMKK6 gene transcription contributes to the
      immune response in cotton.
AB  - Fusarium wilt is a major biotic stress affecting the productivity of cotton
      (Gossypium hirsutum). Although mitogen-activated protein kinase (MAPK) cascades
      play critical roles in plant disease resistance, their intricate regulation under
      fungal stress remains unclear, especially with regards to microRNA-mediated
      regulation of MAPK gene expression. In this study, we report that the MAPK kinase
      gene GhMKK6 and ghr-miR5272a work together in cotton resistance to Fusarium wilt.
      Silencing GhMKK6 in cotton decreased resistance to F. oxysporum by repressing the
      expression of known disease-resistance genes. Furthermore, although GhMKK6 played
      a positive role in disease resistance, excessive GhMKK6 activation caused an
      excessive hypersensitive response. ghr-miR5272a, a major regulator, prevents this
      excessive response by regulating GhMKK6 expression. ghr-miR5272a targets the
      GhMKK6 3'-untranslated region in cotton. Overexpressing miR5272a decreased the
      expression of GhMKK6 and disease-resistance genes, and increased sensitivity to
      F. oxysporum, yielding a similar phenotype to GhMKK6-silenced cotton. Overall,
      these results demonstrate that the ghr-miR5272a-mediated regulation of GhMKK6
      expression contributes to the immune response in cotton, and reveal a new
      feedback loop mechanism in plant disease response.

PMID- 29069455
TI  - Haustorium initiation in the obligate parasitic plant Phelipanche ramosa involves
      a host-exudated cytokinin signal.
AB  - The heterotrophic lifestyle of parasitic plants relies on the development of the
      haustorium, a specific infectious organ required for attachment to host roots.
      While haustorium development is initiated upon chemodetection of host-derived
      molecules in hemiparasitic plants, the induction of haustorium formation remains
      largely unknown in holoparasitic species such as Phelipanche ramosa. This work
      demonstrates that the root exudates of the host plant Brassica napus contain
      allelochemicals displaying haustorium-inducing activity on P. ramosa germinating
      seeds, which increases the parasite aggressiveness. A de novo assembled
      transcriptome and microarray approach with P. ramosa during early haustorium
      formation upon treatment with B. napus root exudates allowed the identification
      of differentially expressed genes involved in hormone signaling. Bioassays using
      exogenous cytokinins and the specific cytokinin receptor inhibitor PI-55 showed
      that cytokinins induced haustorium formation and increased parasite
      aggressiveness. Root exudates triggered the expression of cytokinin-responsive
      genes during early haustorium development in germinated seeds, and bio-guided
      UPLC-ESI(+)-/MS/MS analysis showed that these exudates contain a cytokinin with
      dihydrozeatin characteristics. These results suggest that cytokinins
      constitutively exudated from host roots play a major role in haustorium formation
      and aggressiveness in P. ramosa.

PMID- 29069456
TI  - Thyroid State Regulates Gene Expression in Human Whole Blood.
AB  - Context: Despite the well-recognized clinical features resulting from
      insufficient or excessive thyroid hormone (TH) levels in humans, it is largely
      unknown which genes are regulated by TH in human tissues. Objective: To study the
      effect of TH on human gene expression profiles in whole blood, mainly consisting
      of T3 receptor (TR) alpha-expressing cells. Methods: We performed next-generation
      RNA sequencing on whole blood samples from eight athyroid patients (four females)
      on and after 4 weeks off levothyroxine replacement. Gene expression changes were
      analyzed through paired differential expression analysis and confirmed in a
      validation cohort. Weighted gene coexpression network analysis (WGCNA) was
      applied to identify thyroid state-related networks. Results: We detected 486
      differentially expressed genes (fold-change >1.5; multiple testing corrected P
      value < 0.05), of which 76% were positively and 24% were negatively regulated.
      Gene ontology (GO) enrichment analysis revealed that three biological processes
      were significantly overrepresented, of which the process translational elongation
      showed the highest fold enrichment (7.3-fold, P = 1.8 * 10-6). WGCNA analysis
      independently identified various gene clusters that correlated with thyroid
      state. Further GO analysis suggested that thyroid state affects platelet
      function. Conclusions: Changes in thyroid state regulate numerous genes in human
      whole blood, predominantly TRalpha-expressing leukocytes. In addition, TH may
      regulate gene transcripts in platelets.

PMID- 29069458
TI  - Cholesterol variability and the risk of mortality, myocardial infarction, and
      stroke: a nationwide population-based study.
AB  - Aims: A high visit-to-visit variability in cholesterol levels has been suggested
      to be an independent predictor of major adverse cardiovascular events in patients
      with coronary artery disease (CAD). Because whether this notion applies to
      general population is not known, we aimed to investigate the associations between
      total cholesterol (TC) variability and the risk of all-cause mortality,
      myocardial infarction (MI), and stroke. Methods and results: We identified 3 656
      648 subjects without a history of MI and stroke who underwent >=3 health
      examinations from 2002 to 2007 in the Korean National Health Insurance System
      cohort. Total cholesterol variability was measured using the coefficient of
      variation (CV), standard deviation (SD), and variability independent of the mean
      (VIM). There were 84 625 deaths (2.3%), 40 991 cases of MI (1.1%), and 42 861
      cases of stroke (1.2%) during the median follow-up of 8.3 years. There was a
      linear association between higher TC variability and outcome measures. In the
      multivariable adjusted model, the hazard ratios and 95% confidence intervals
      comparing the highest vs. lowest quartiles of CV of TC were 1.26 (1.24-1.28) for
      all-cause mortality, 1.08 (1.05-1.11) for MI, and 1.11 (1.08-1.14) for stroke,
      which was independent of mean TC levels and the use of lipid-lowering agents. The
      results were consistent when modelling variability of TC using SD and VIM, and in
      various sensitivity analyses. Conclusion: High variability in lipid levels is
      associated with adverse health-related outcomes. These findings suggest that
      lipid variability is an important risk factor in the general population.

PMID- 29069457
TI  - Nol12 is a multifunctional RNA binding protein at the nexus of RNA and DNA
      metabolism.
AB  - To counteract the breakdown of genome integrity, eukaryotic cells have developed
      a network of surveillance pathways to prevent and resolve DNA damage. Recent data
      has recognized the importance of RNA binding proteins (RBPs) in DNA damage repair
      (DDR) pathways. Here, we describe Nol12 as a multifunctional RBP with roles in
      RNA metabolism and genome maintenance. Nol12 is found in different subcellular
      compartments-nucleoli, where it associates with ribosomal RNA and is required for
      efficient separation of large and small subunit precursors at site 2; the
      nucleoplasm, where it co-localizes with the RNA/DNA helicase Dhx9 and
      paraspeckles; as well as GW/P-bodies in the cytoplasm. Loss of Nol12 results in
      the inability of cells to recover from DNA stress and a rapid p53-independent ATR
      Chk1-mediated apoptotic response. Nol12 co-localizes with DNA repair proteins in
      vivo including Dhx9, as well as with TOPBP1 at sites of replication stalls,
      suggesting a role for Nol12 in the resolution of DNA stress and maintenance of
      genome integrity. Identification of a complex Nol12 interactome, which includes
      NONO, Dhx9, DNA-PK and Stau1, further supports the protein's diverse functions in
      RNA metabolism and DNA maintenance, establishing Nol12 as a multifunctional RBP
      essential for genome integrity.

PMID- 29069459
TI  - OverGeneDB: a database of 5' end protein coding overlapping genes in human and
      mouse genomes.
AB  - Gene overlap plays various regulatory functions on transcriptional and post
      transcriptional levels. Most current studies focus on protein-coding genes
      overlapping with non-protein-coding counterparts, the so called natural antisense
      transcripts. Considerably less is known about the role of gene overlap in the
      case of two protein-coding genes. Here, we provide OverGeneDB, a database of
      human and mouse 5' end protein-coding overlapping genes. The database contains
      582 human and 113 mouse gene pairs that are transcribed using overlapping
      promoters in at least one analyzed library. Gene pairs were identified based on
      the analysis of the transcription start site (TSS) coordinates in 73 human and 10
      mouse organs, tissues and cell lines. Beside TSS data, resources for 26 human
      lung adenocarcinoma cell lines also contain RNA-Seq and ChIP-Seq data for seven
      histone modifications and RNA Polymerase II activity. The collected data revealed
      that the overlap region is rarely conserved between the studied species and
      tissues. In ~50% of the overlapping genes, transcription started explicitly in
      the overlap regions. In the remaining half of overlapping genes, transcription
      was initiated both from overlapping and non-overlapping TSSs. OverGeneDB is
      accessible at http://overgenedb.amu.edu.pl.

PMID- 29069460
TI  - CHARACTERIZATION OF FLUORESCENT NUCLEAR TRACK DETECTORS AS CRITICALITY DOSIMETERS
      II.
AB  - Fluorescent nuclear track detectors (FNTDs) as criticality dosimeters for both
      neutrons and gamma are further characterized in terms of angular dependence and
      quick dose assessment. The power spectrum integral depth profiles obtained from
      stacks of fluorescent images acquired within FNTDs exposed to a broad spectrum
      neutron field at various angles are analyzed to determine a calibration curve for
      angular dependence. MCNPX simulations were shown to be in good agreement with
      experimental results. A prototype triage reader was also designed and tested for
      quick assessment of dose. An unfolding technique incorporating both energy
      dependence and angular dependence is discussed. The advantages and shortcomings
      of using FNTDs in the event of a criticality excursion accident are analyzed.

PMID- 29069461
TI  - XdhR negatively regulates actinorhodin biosynthesis in Streptomyces coelicolor
      M145.
AB  - The xdhR gene encodes a TetR-family regulator in Streptomyces coelicolor.
      However, little is known about the function of XdhR in regulating actinorhodin
      production. Here, we report that XdhR negatively regulates actinorhodin
      biosynthesis in S. coelicolor. Deletion of xdhR resulted in overproduction of
      actinorhodin by approximately 2.5-fold compared to the wild-type strain.
      Complementation of the xdhR deletion strain restored actinorhodin production to
      normal levels. In addition, the relative expression levels of actinorhodin
      cluster genes were all significantly increased in the xdhR deletion strain
      compared to the wild-type strain. XdhR can specifically bind the promoters of
      actII-4 and actII-1, two pathway-specific regulators of actinorhodin
      biosynthesis. These results suggest that xdhR negatively controls actinorhodin
      biosynthesis by directly regulating actII-4 and actII-1 in S. coelicolor.

PMID- 29069463
TI  - Combination of DNA ploidy analysis and miR-21 or miR-24 in screening malignant
      pleural effusion.
AB  - OBJECTIVES: The study aimed to assess the combination of DNA ploidy analysis
      (DPA) and the expression of microRNA-21 (miR-21) or microRNA-24 (miR-24) in the
      detection of malignant pleural effusion (MPE). METHODS: In this prospective
      research, a total of 40 samples (20 benign and 20 malignant effusions), flexural
      effusion exfoliated cells and cell-free miR-21 and miR-24 were collected. DPA and
      exfoliative cytology examinations were conducted to diagnose flexural effusion
      exfoliated cells. Quantitative reverse transcriptase polymerase chain reaction
      was carried out to measure the expressions of miR-21 and miR-24. Receiver
      operating characteristic curve and the area under the curve were applied to
      evaluate the accuracy rate of different diagnostic approaches on MPE. RESULTS: In
      the MPE group, DPA demonstrated a higher rate of accuracy in MPE diagnosis than
      exfoliative cytology. The expressions of miR-21 and miR-24 were significantly
      higher in MPE than in benign pleural effusion (P < 0.05). Furthermore, area under
      the curve, sensitivity and specificity were 0.942, 95% and 90% for the
      combination of miR-21 and DPA and 0.973, 100% and 80% for the union of miR-24 and
      DPA, respectively, representing a significant improvement in both accuracy and
      sensitivity. Therefore, the combination of DPA and miR-21 or miR-24 appears to be
      a better biomarker for discriminating MPE from benign pleural effusion.
      CONCLUSIONS: The combination of DPA and miR-21 or miR-24 may function as a
      promising diagnostic tool of MPE. Registration number: ChiCTR-TRC-14004719.

PMID- 29069462
TI  - Sexually Dimorphic Impact of Chromium Accumulation on Human Placental Oxidative
      Stress and Apoptosis.
AB  - Environmental contamination with hexavalent chromium (CrVI) is a growing problem
      both in the United States and developing countries. Hexavalent chromium is widely
      used in numerous industries. Environmental exposure to CrVI adversely affects
      pregnancy outcomes and subsequent health of 2 generations, resulting in higher
      pregnancy loss, spontaneous abortion and low birth rate. Pregnant women exposed
      to CrVI through occupational settings experience increased risk of spontaneous
      abortion, stillbirth, preterm birth, and neonatal death. Children of the CrVI
      exposed women experience respiratory problems, perinatal jaundice, and increased
      birth defects. Because placental dysfunction may have a role in such adverse
      pregnancy outcome, we tested the hypothesis that environmental Cr exposure in
      pregnant women results in Cr accumulation in the human placenta, which could
      increase placental oxidative stress by disrupting antioxidant machinery and
      inducing apoptosis. Studies using frozen, deidentified human term placenta
      samples indicated that: (1) Cr accumulates in human term placenta tissues and (2)
      increase in Cr accumulation is positively correlated with oxidative stress and
      apoptotic markers, and altered antioxidants levels. Interestingly, there was a
      sexual dimorphism in the correlation between Cr accumulation and oxidative
      stress, and expression of apoptotic and antioxidant markers. Mechanistic in vitro
      studies using human trophoblast cells BeWo confirmed the detrimental effects of
      Cr in altering antioxidant genes. For the first time, this study provides
      evidence in support of a positive correlation between Cr accumulation in the
      human placenta and accelerated oxidative stress, with a gender bias toward the
      male sex.

PMID- 29069464
TI  - Sleep as a Target for Optimized Response to Smoking Cessation Treatment.
AB  - Abstract: Declining national rates of current tobacco use to an all-time low of
      15.1% represents a public health victory. Undermining this progress, however, are
      smoking rates of up to 50% among high-risk, low-income populations. Current FDA
      approved treatments for nicotine dependence are ineffective with between 70-95%
      of treatment-seekers relapsing within the first year of attempted abstinence.
      Thus, identification of novel intervention targets to optimize response to
      currently available treatments for nicotine dependence is a critical next step.
      One such target may be sleep insomnia. Insomnia is a clinically verified nicotine
      withdrawal symptom but, to date, addressing insomnia or other sleep disturbance
      symptoms as an adjunctive smoking cessation therapy has yet to be fully
      considered. To this end, this manuscript presents a narrative review of: (a)
      sleep continuity and architecture in smokers versus non-smokers; (b) effects of
      nicotine abstinence on sleep; (c) possible mechanisms linking sleep with smoking
      cessation outcomes; (d) plausible adjunctive sleep therapies to promote smoking
      cessation; (e) possible treatments for unhealthy sleep in smokers, and, (f)
      directions for future research. Taken together, this will provide conceptual
      support for sleep therapy as an adjunctive treatment for smoking cessation.
      Implications: This narrative literature review presents a comprehensive
      discussion of the relationship between habitual sleep and cigarette smoking. The
      extent to which unhealthy sleep in smokers may be a viable intervention target
      for promoting response to smoking cessation treatment is considered. Ultimately,
      this review provides conceptual support for sleep therapy as an adjunctive
      treatment for smoking cessation.

PMID- 29069465
TI  - Editor's Highlight: Ethylene Glycol Teratogenicity: A Role for Embryonic
      Acidosis?
AB  - Ethylene glycol (EG) is a developmental toxicant in pregnant rats and mice. A
      suggested mechanism for this toxicity is that the EG metabolite, glycolic acid
      (GA), causes acidosis which may affect the embryonic heart rate (HR). This
      inhibition would cause periods of embryonic bradycardia and arrhythmia resulting
      in increased embryonic death and malformation in surviving embryos. This
      hypothesis was investigated using gestational day (GD) 11 and 13 rat embryos in
      vitro. Increasing concentrations of GA or lactic acid in the incubation medium
      caused a decrease in external pH (pHe) and a concentration-dependent decrease in
      embryonic HR. Increased concentrations of GA or lactic acid with pHe corrected to
      normal levels did not affect HR. Severely decreased pHe, caused by reduced NaHCO3
      in the incubation medium, had little effect on the HR of GD 13 embryos but
      substantially reduced the HR of GD 11 embryos. These results suggest that
      increased monocarboxylate concentration (glycolate or lactate) needs to be in
      combination with increased H+ concentration (low pHe) to influence the embryonic
      HR. These results implicate the monocarboxylate transporter reported to be
      present in the early postnatal rat heart, the chick embryonic heart throughout
      development, and the chorioallantoic placenta. The results showed some evidence
      that the adverse effect of GA and reduced pHe on the embryonic HR increased with
      duration of exposure and hence lends support to the suggested mechanism of
      embryotoxicity for EG.

PMID- 29069466
TI  - MGA repository: a curated data resource for ChIP-seq and other genome annotated
      data.
AB  - The Mass Genome Annotation (MGA) repository is a resource designed to store
      published next generation sequencing data and other genome annotation data (such
      as gene start sites, SNPs, etc.) in a completely standardised format. Each sample
      has undergone local processing in order the meet the strict MGA format
      requirements. The original data source, the reformatting procedure and the
      biological characteristics of the samples are described in an accompanying
      documentation file manually edited by data curators. 10 model organisms are
      currently represented: Homo sapiens, Mus musculus, Danio rerio, Drosophila
      melanogaster, Apis mellifera, Caenorhabditis elegans, Arabidopsis thaliana, Zea
      mays, Saccharomyces cerevisiae and Schizosaccharomyces pombe. As of today, the
      resource contains over 24 000 samples. In conjunction with other tools developed
      by our group (the ChIP-Seq and SSA servers), it allows users to carry out a great
      variety of analysis task with MGA samples, such as making aggregation plots and
      heat maps for selected genomic regions, finding peak regions, generating custom
      tracks for visualizing genomic features in a UCSC genome browser window, or
      downloading chromatin data in a table format suitable for local processing with
      more advanced statistical analysis software such as R. Home page:
      http://ccg.vital-it.ch/mga/.

PMID- 29069467
TI  - Risk-taking, peer-influence and child maltreatment: a neurocognitive
      investigation.
AB  - Maltreatment is associated with increased risk of a range of psychiatric
      disorders, many of which are characterized by altered risk-taking propensity.
      Currently, little is known about the neural correlates of risk-taking in children
      exposed to maltreatment, nor whether their risk-taking is atypically modulated by
      peer influence. Seventy-five 10- to 14-year-old children [maltreated (MT) group:
      N = 41; non-maltreated Group (NMT): N = 34] performed a Balloon Analogue Risk
      Task (BART), under three different peer influence conditions: while alone, while
      being observed by a peer and while being encouraged by a peer to take risks. The
      MT group engaged in less risk-taking irrespective of peer influence. There was no
      differential effect of peer influence on risk-taking behaviour across groups. At
      the neural level, the right anterior insula (rAI) exhibited altered risk
      sensitivity across conditions in the MT group. Across groups and conditions, rAI
      risk sensitivity was negatively associated with risk-taking and within the MT
      group greater rAI risk sensitivity was related to more anxiety symptoms. These
      findings suggest that children with a history of maltreatment show reduced risk
      taking but typical responses to peer influence. Abnormal rAI functioning
      contributes to the pattern of reduced risk-taking and may predispose children
      exposed to maltreatment to develop future psychopathology.

PMID- 29069468
TI  - Leukocyte Dynamics Influence Reference Gene Stability in Whole Blood: Data-Driven
      qRT-PCR Normalization Is a Robust Alternative for Measurement of Transcriptional
      Biomarkers.
AB  - Background: The use of reference genes for normalization of whole blood qRT-PCR
      data may be problematic in conditions such as stroke which induce alterations in
      white blood cell differential. In this study, we assessed the influence of stroke
      on the stability of commonly employed reference genes, and we evaluated data
      driven normalization as an alternative. Methods: Peripheral whole blood was
      sampled from 33 stroke patients and 29 controls, and qRT-PCR was used to measure
      the expression levels of 10 target genes whose transcripts are known stroke
      biomarkers. Target gene expression levels were normalized via those of 2
      frequently cited reference genes (ACTB and B2M) as well as with the NORMA-Gene
      data-driven normalization algorithm. Results: Whole blood expression levels of
      reference genes were significantly altered in stroke patients relative to
      controls. In comparison to normalization via reference genes, NORMA-Gene produced
      more robust target gene expression data in terms of differential expression
      dynamics, variance properties, and diagnostic performance. Conclusions: Our
      findings suggest that whole blood expression levels of commonly used reference
      genes may be sensitive to changes in white blood cell differential, and that data
      driven qRT-PCR normalization approaches offer a powerful alternative.

PMID- 29069469
TI  - Polysome-profiling in small tissue samples.
AB  - Polysome-profiling is commonly used to study translatomes and applies laborious
      extraction of efficiently translated mRNA (associated with >3 ribosomes) from a
      large volume across many fractions. This property makes polysome-profiling
      inconvenient for larger experimental designs or samples with low RNA amounts. To
      address this, we optimized a non-linear sucrose gradient which reproducibly
      enriches for efficiently translated mRNA in only one or two fractions, thereby
      reducing sample handling 5-10-fold. The technique generates polysome-associated
      RNA with a quality reflecting the starting material and, when coupled with smart
      seq2 single-cell RNA sequencing, translatomes in small tissues from biobanks can
      be obtained. Translatomes acquired using optimized non-linear gradients resemble
      those obtained with the standard approach employing linear gradients. Polysome
      profiling using optimized non-linear gradients in serum starved HCT-116 cells
      with or without p53 showed that p53 status associates with changes in mRNA
      abundance and translational efficiency leading to changes in protein levels.
      Moreover, p53 status also induced translational buffering whereby changes in mRNA
      levels are buffered at the level of mRNA translation. Thus, here we present a
      polysome-profiling technique applicable to large study designs, primary cells and
      frozen tissue samples such as those collected in biobanks.

PMID- 29069470
TI  - Common TFIIH recruitment mechanism in global genome and transcription-coupled
      repair subpathways.
AB  - Nucleotide excision repair is initiated by two different damage recognition
      subpathways, global genome repair (GGR) and transcription-coupled repair (TCR).
      In GGR, XPC detects DNA lesions and recruits TFIIH via interaction with the
      pleckstrin homology (PH) domain of TFIIH subunit p62. In TCR, an elongating form
      of RNA Polymerase II detects a lesion on the transcribed strand and recruits
      TFIIH by an unknown mechanism. Here, we found that the TCR initiation factor
      UVSSA forms a stable complex with the PH domain of p62 via a short acidic string
      in the central region of UVSSA, and determined the complex structure by NMR. The
      acidic string of UVSSA binds strongly to the basic groove of the PH domain by
      inserting Phe408 and Val411 into two pockets, highly resembling the interaction
      mechanism of XPC with p62. Mutational binding analysis validated the structure
      and identified residues crucial for binding. TCR activity was markedly diminished
      in UVSSA-deficient cells expressing UVSSA mutated at Phe408 or Val411. Thus, a
      common TFIIH recruitment mechanism is shared by UVSSA in TCR and XPC in GGR.

PMID- 29069471
TI  - Serious infusion-related reaction after rituximab, abatacept and tocilizumab in
      rheumatoid arthritis: prospective registry data.
AB  - Objective: The aim was to evaluate the incidence of serious infusion-related
      reactions (SIRRs) in RA treated by non-TNF-targeted biologics. Methods: We
      analysed data from three independent prospective registers, namely autoimmunity
      and rituximab, Orencia (abatacept) and RA (ORA) and Registry RoAcTEmra
      (tocilizumab), promoted by the French Society of Rheumatology and including
      patients with RA. SIRRs were defined by an occurrence during or within 24 h of an
      infusion and requiring discontinuation of treatment. Characteristics of patients
      with SIRRs were extracted from the electronic database. Results: Among the 4145
      patients, SIRRs occurred in 100 patients: 56 patients with the rituximab cohort
      (2.8% or 0.7/100 patient-years), 15 with the abatacept cohort (1.5% or 0.6/100
      patient-years) and 29 with tocilizumab (1.9% or 1/100 patient-years). No fatal
      SIRR occurred. A previous mild infusion reaction to non-TNF-targeted biologics
      was observed in a quarter of patients with SIRRs. After pooled multivariate
      analysis, positive anti-CCP was associated with a higher risk of SIRR (odds ratio
      = 2.5; 95% CI: 1.01, 6.17). Absence of concomitant treatment with a synthetic
      DMARD tended to be associated with a higher risk of SIRR (odds ratio = 1.67; 95%
      CI: 1.00, 2.86). Conclusion: In daily practice, SIRRs are slightly more frequent
      than in clinical trials and rarely life threatening. In common practice,
      serological status (anti-CCP positivity) and absence of concomitant treatment
      with a synthetic DMARD increase the risk of SIRR.

PMID- 29069472
TI  - Pupation Behaviors and Emergence Successes of Ectropis grisescens (Lepidoptera:
      Geometridae) in Response to Different Substrate Types and Moisture Contents.
AB  - Ectropis grisescens Warren (Lepidoptera: Geometridae) is one of the most severe
      pests of tea plants in China. This species commonly pupates in soil; however,
      little is known about its pupation ecology. In the present study, choice and no
      choice tests were conducted to investigate the pupation behaviors and emergence
      success of E. grisescens in response to different substrates (sand, sandy loam 1,
      sandy loam 2, and silt loam) and moisture contents (5, 20, 35, 50, 65, and 80%).
      Moisture-choice bioassays showed that significantly more E. grisescens
      individuals pupated in or on soil (sandy loam 1 and 2 and silt loam) that was at
      the intermediate moisture levels, whereas 5%- and 35%-moisture sand was
      significantly more preferred over 80%-moisture sand for pupating. Substrate
      choice bioassays showed that sand was most preferred by E. grisescens individuals
      at 20%- and 80%-moisture levels, but no preference was detected among the four
      substrates at 50%-moisture content. No-choice tests showed that the percentage of
      burrowed E. grisescens individuals and pupation depth were significantly lower
      when soil was dry (20% moisture) or wet (80% moisture). In addition, 20%-moisture
      sandy loam 2 and silt loam significantly decreased the body water content of
      pupae and emergence success of adults compared to 50%-moisture content. However,
      each measurement (percentage of burrowed individuals, pupation depth, body water
      content, or emergence success) was similar when compared among different moisture
      levels of sand. Interestingly, pupae buried with 80%-moisture soil exhibited
      significantly lower emergence success than that were unburied.

PMID- 29069473
TI  - Genome Variation Map: a data repository of genome variations in BIG Data Center.
AB  - The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data
      repository of genome variations. As a core resource in the BIG Data Center,
      Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to
      collect, integrate and visualize genome variations for a wide range of species,
      accepts submissions of different types of genome variations from all over the
      world and provides free open access to all publicly available data in support of
      worldwide research activities. Unlike existing related databases, GVM features
      integration of a large number of genome variations for a broad diversity of
      species including human, cultivated plants and domesticated animals.
      Specifically, the current implementation of GVM not only houses a total of ~4.9
      billion variants for 19 species including chicken, dog, goat, human, poplar, rice
      and tomato, but also incorporates 8669 individual genotypes and 13 262 manually
      curated high-quality genotype-to-phenotype associations for non-human species. In
      addition, GVM provides friendly intuitive web interfaces for data submission,
      browse, search and visualization. Collectively, GVM serves as an important
      resource for archiving genomic variation data, helpful for better understanding
      population genetic diversity and deciphering complex mechanisms associated with
      different phenotypes.

PMID- 29069474
TI  - The Validity and Value of Self-reported Physical Activity and Accelerometry in
      People With Schizophrenia: A Population-Scale Study of the UK Biobank.
AB  - Background: Previous physical activity (PA) research in schizophrenia has relied
      largely upon self-report measures. However, the accuracy of this method is
      questionable. Obtaining accurate measurements, and determining what may influence
      PA levels in schizophrenia, is essential to understand physical inactivity in
      this population. This study examined differences in self-reported and objectively
      measured PA in people with schizophrenia and the general population using a
      large, population-based dataset from the UK Biobank. Methods: Baseline data from
      the UK Biobank (2007-2010) were analyzed; including 1078 people with
      schizophrenia (54.19 +/- 8.39 years; 55% male) and 450549 without (56.44 +/-
      8.11; 46% male). We compared self-reported PA with objectively measured
      accelerometry data in schizophrenia and comparison samples. We also examined
      correlations between self-report and objective measures. Results: People with
      schizophrenia reported the same PA levels as those without, with no differences
      in low, moderate, or vigorous intensity activity. However, accelerometry data
      showed a large and statistically significant reduction of PA in schizophrenia; as
      people with schizophrenia, on average, engaged in less PA than 80% of the general
      population. Nonetheless, within the schizophrenia sample, total self-reported PA
      still held significant correlations with objective measures. Conclusions: People
      with schizophrenia are significantly less active than the general population.
      However, self-report measures in epidemiological studies fail to capture the
      reduced activity levels in schizophrenia. This also has implications for self
      report measures of other lifestyle factors which may contribute toward the poor
      health outcomes observed in schizophrenia. Nonetheless, self-report measures may
      still be useful for identifying how active individuals with schizophrenia
      relative to other patients.

PMID- 29069475
TI  - APPRIS 2017: principal isoforms for multiple gene sets.
AB  - The APPRIS database (http://appris-tools.org) uses protein structural and
      functional features and information from cross-species conservation to annotate
      splice isoforms in protein-coding genes. APPRIS selects a single protein isoform,
      the 'principal' isoform, as the reference for each gene based on these
      annotations. A single main splice isoform reflects the biological reality for
      most protein coding genes and APPRIS principal isoforms are the best predictors
      of these main proteins isoforms. Here, we present the updates to the database,
      new developments that include the addition of three new species (chimpanzee,
      Drosophila melangaster and Caenorhabditis elegans), the expansion of APPRIS to
      cover the RefSeq gene set and the UniProtKB proteome for six species and
      refinements in the core methods that make up the annotation pipeline. In addition
      APPRIS now provides a measure of reliability for individual principal isoforms
      and updates with each release of the GENCODE/Ensembl and RefSeq reference sets.
      The individual GENCODE/Ensembl, RefSeq and UniProtKB reference gene sets for six
      organisms have been merged to produce common sets of splice variants.

PMID- 29069476
TI  - EBI Metagenomics in 2017: enriching the analysis of microbial communities, from
      sequence reads to assemblies.
AB  - EBI metagenomics (http://www.ebi.ac.uk/metagenomics) provides a free to use
      platform for the analysis and archiving of sequence data derived from the
      microbial populations found in a particular environment. Over the past two years,
      EBI metagenomics has increased the number of datasets analysed 10-fold. In
      addition to increased throughput, the underlying analysis pipeline has been
      overhauled to include both new or updated tools and reference databases. Of
      particular note is a new workflow for taxonomic assignments that has been
      extended to include assignments based on both the large and small subunit RNA
      marker genes and to encompass all cellular micro-organisms. We also describe the
      addition of metagenomic assembly as a new analysis service. Our pilot studies
      have produced over 2400 assemblies from datasets in the public domain. From these
      assemblies, we have produced a searchable, non-redundant protein database of over
      50 million sequences. To provide improved access to the data stored within the
      resource, we have developed a programmatic interface that provides access to the
      analysis results and associated sample metadata. Finally, we have integrated the
      results of a series of statistical analyses that provide estimations of diversity
      and sample comparisons.

PMID- 29069477
TI  - Cluster-Level Relationships of Genes Involved in Carbon Metabolism in
      Synechocystis sp. PCC 6803: Development of a Novel Succinate-Producing Strain.
AB  - We quantified the transcript levels of 44 genes related to sugar catabolism in
      strains with altered primary carbon metabolism and discovered a consistent
      expression pattern among succinate-producing mutants. To identify factors that
      determine the expression pattern, we calculated Pearson's correlation
      coefficients, using the transcript data. Correlation analysis revealed positive
      and negative correlations among genes encoding sugar catabolic enzymes. On the
      basis of this analysis, we found that the mutant overexpressing both rre37
      (encoding an OmpR-type response regulator) and sigE (encoding an RNA polymerase
      sigma factor) produced increased levels of succinate under dark, anaerobic
      conditions, with a maximum productivity of 420 mg l-1.

PMID- 29069478
TI  - Cannulation strategy for centrifugal-flow ventricular assist device implantation
      late after arterial switch operation.
AB  - The field of paediatric ventricular assist device (VAD) support is growing
      rapidly. Among paediatric patients, those with complex congenital heart disease
      represent a challenging population for VAD support. This report describes a
      patient with a remote history of an arterial switch operation for d-transposition
      of the great arteries who developed ischaemic cardiomyopathy necessitating
      centrifugal-flow VAD support as a bridge to cardiac transplantation. Because of
      the unique anatomy and the complicated vascular situation, implantation of the
      centrifugal-flow VAD and subsequent explantation for cardiac transplantation
      required modifications to the standard surgical approach. The details of surgical
      pitfalls encountered are described.

PMID- 29069479
TI  - FlyAtlas 2: a new version of the Drosophila melanogaster expression atlas with
      RNA-Seq, miRNA-Seq and sex-specific data.
AB  - FlyAtlas 2 (www.flyatlas2.org) is part successor, part complement to the FlyAtlas
      database and web application for studying the expression of the genes of
      Drosophila melanogaster in different tissues of adults and larvae. Although
      generated in the same lab with the same fly line raised on the same diet as
      FlyAtlas, the FlyAtlas2 resource employs a completely new set of expression data
      based on RNA-Seq, rather than microarray analysis, and so it allows the user to
      obtain information for the expression of different transcripts of a gene.
      Furthermore, the data for somatic tissues are now available for both male and
      female adult flies, allowing studies of sexual dimorphism. Gene coverage has been
      extended by the inclusion of microRNAs and many of the RNA genes included in
      Release 6 of the Drosophila reference genome. The web interface has been modified
      to accommodate the extra data, but at the same time has been adapted for viewing
      on small mobile devices. Users also have access to the RNA-Seq reads displayed
      alongside the annotated Drosophila genome in the (external) UCSC browser, and are
      able to link out to the previous FlyAtlas resource to compare the data obtained
      by RNA-Seq with that obtained using microarrays.

PMID- 29069480
TI  - RADON SURVEY IN SCHOOL AND ESTIMATION OF EFFECTIVE DOSE USING CORRECTED RADON
      CONCENTRATION.
AB  - Radon exposure in schools is different from that in dwellings because the
      residence pattern is very different each other. So, when effective dose is
      calculated in schools, different approach should be considered from in dwellings.
      The aim of this study was to estimate actual effective dose due to inhaled radon
      considering the residence time in schools. It could help avoid overestimation
      when effective dose is calculated in schools. The range of radon concentration in
      376 schools was 18.1-2810 Bq m-3 and that of annual effective dose was estimated
      0.0902-8.92 mSv y-1 considering the residence time in spring and autumn
      semesters.

PMID- 29069481
TI  - Enhanced Cold Tolerance and Tillering in Switchgrass (Panicum virgatum L.) by
      Heterologous Expression of Osa-miR393a.
AB  - The microRNA393 (miR393) family is one of the conserved miRNA families in the
      plant kingdom. MiR393 was reported to regulate rice tillering and abiotic stress
      resistance positively through an auxin signaling pathway. However, little is
      known about the function of miR393 in switchgrass (Panicum virgatum L.), an
      important bioenergy C4 grass plant. We tested the expression level of miR393 and
      its four putative target genes (PvAFB1, PvAFB2, PvAFB3 and PvTIR1) in
      switchgrass, and found that these genes all responded to cold stress and
      exogenous 1-naphthaleneacetic acid (NAA) treatment. To investigate the function
      of miR393 in switchgrass, we enhanced miR393 expression by introducing an Osa
      miR393a gene into switchgrass. The results showed that cold tolerance of the
      transgenic T0 and T1 generation plants was highly improved. Cold tolerance
      related genes PvCOR47, PvICE1 and PvRAV1 were negatively regulated by exogenous
      NAA, and the expression of these genes was significantly higher in transgenic
      plants than in wild-type plants. The transgenic T1 seedlings were more tolerant
      to exogenous NAA treatment, accumulating less H2O2 after cold treatments. It was
      also observed that the miR393/target module regulates cold tolerance responses in
      Arabidopsis. In addition, transgenic plants overexpressing miR393 had
      significantly more tillers and higher biomass yield per plant in greenhouse and
      field tests. Forage quality analyses revealed that the soluble sugar contents of
      transgenic plants were increased markedly. Overall, the results suggested that
      overexpression of miR393 improved cold tolerance and tillering of switchgrass
      through regulation of auxin signaling transduction.

PMID- 29069484
TI  - Dual-process theory and consumer response to front-of-package nutrition label
      formats.
AB  - Nutrition labeling literature yields fragmented results about the effect of front
      of-package (FOP) nutrition label formats on healthy food choice. Specifically, it
      is unclear which type of nutrition label format is effective across different
      shopping situations. To address this gap, the present review investigates the
      available nutrition labeling literature through the prism of dual-process theory,
      which posits that decisions are made either quickly and automatically (system 1)
      or slowly and deliberately (system 2). A systematically performed review of
      nutrition labeling literature returned 59 papers that provide findings that can
      be explained according to dual-process theory. The findings of these studies
      suggest that the effectiveness of nutrition label formats is influenced by the
      consumer's dominant processing system, which is a function of specific contexts
      and personal variables (eg, motivation, nutrition knowledge, time pressure, and
      depletion). Examination of reported findings through a situational processing
      perspective reveals that consumers might prefer different FOP nutrition label
      formats in different situations and can exhibit varying responses to the same
      label format across situations. This review offers several suggestions for policy
      makers and researchers to help improve current FOP nutrition label formats.

PMID- 29069485
TI  - Assessing Genetic Diversity in Four Stink Bug Species, Chinavia hilaris,
      Chlorochroa uhleri, Chlorochroa sayi, and Thyanta pallidovirens (Hemiptera:
      Pentatomidae), Using DNA Barcodes.
AB  - Stink bugs (Hemiptera: Pentatomidae) are an economically important group of
      insects that attack numerous crops in the central valley of California.
      Management of these pests using pheromones or biological control can be species
      specific, and proper identification of insect species is essential for effective
      management. The objective was to examine genetic variability in four species of
      stink bugs, which included Chinavia hilaris (Say) (= Acrosternum hilare)
      (Hemiptera: Pentatomidae) , Chlorochroa uhleri (Stal) (Hemiptera: Pentatomidae) ,
      Chlorochroa sayi (Stal) (Hemiptera: Pentatomidae), and Thyanta pallidovirens
      (Stal) (Hemiptera: Pentatomidae) and to determine whether there may be cryptic
      species present. Stink bugs were collected in pistachios or on adjacent
      vegetation when abundant in the central valley of California. The mitochondrial
      DNA cytochrome oxidase I (COI) gene region (i.e., the barcode) was sequenced for
      each individual. Data were combined with available GenBank accessions for each
      species and used to construct a phylogenetic tree. Divergence between genera
      ranged from 11.2 to 15.7%, whereas divergence between the two Chlorochroa spp.
      was 4.6%. Genetic variation within Chinavia hilaris collections was up to 4.7%,
      which suggests the presence of a cryptic species. Genetic divergence was highest
      between individuals of Chinavia hilaris from the west coast and the east coast of
      the United States. In contrast, genetic variation within individuals of C. uhleri
      and Ch. sayi was less than 1%. Nine haplotypes were found for Chinavia hilaris,
      five for C. uhleri, three for Ch. sayi, and five for T. pallidovirens. The
      relevance of correct species identification and genetic diversity to stink bug
      management practices was discussed.

PMID- 29069483
TI  - Protein profile of mouse ovarian follicles grown in vitro.
AB  - STUDY QUESTION: Could the follicle proteome be mapped by identifying specific
      proteins that are common or differ between three developmental stages from the
      secondary follicle (SF) to the antrum-like stage? SUMMARY ANSWER: From a total of
      1401 proteins identified in the follicles, 609 were common to the three
      developmental stages investigated and 444 were found uniquely at one of the
      stages. WHAT IS KNOWN ALREADY: The importance of the follicle as a functional
      structure has been recognized; however, up-to-date the proteome of the whole
      follicle has not been described. A few studies using proteomics have previously
      reported on either isolated fully-grown oocytes before or after meiosis
      resumption or cumulus cells. STUDY DESIGN, SIZE, DURATION: The experimental
      design included a validated mice model for isolation and individual culture of
      SFs. The system was chosen as it allows continuous evaluation of follicle growth
      and selection of follicles for analysis at pre-determined developmental stages:
      SF, complete Slavjanski membrane rupture (SMR) and antrum-like cavity (AF). The
      experiments were repeated 13 times independently to acquire the material that was
      analyzed by proteomics. PARTICIPANTS/MATERIALS, SETTING, METHODS: SFs (n = 2166)
      were isolated from B6CBA/F1 female mice (n = 42), 12 days old, from 15 l. About
      half of the follicles isolated as SF were analyzed as such (n = 1143) and pooled
      to obtain 139 MUg of extracted protein. Both SMR (n = 359) and AF (n = 124) were
      obtained after individual culture of 1023 follicles in a microdrop system under
      oil, selected for analysis and pooled, to obtain 339 MUg and 170 MUg of protein,
      respectively. The follicle proteome was analyzed combining isoelectric focusing
      (IEF) fractionation with 1D and 2D LC-MS/MS analysis to enhance protein
      identification. The three protein lists were submitted to the 'Compare gene list'
      tool in the PANTHER website to gain insights on the Gene Ontology Biological
      processes present and to Ingenuity Pathway Analysis to highlight protein
      networks. A label-free quantification was performed with 1D LC-MS/MS analyses to
      emphasize proteins with different expression profiles between the three
      follicular stages. Supplementary western blot analysis (using new biological
      replicates) was performed to confirm the expression variations of three proteins
      during follicle development in vitro. MAIN RESULTS AND THE ROLE OF CHANCE: It was
      found that 609 out of 1401 identified proteins were common to the three follicle
      developmental stages investigated. Some proteins were identified uniquely at one
      stage: 71 of the 775 identified proteins in SF, 181 of 1092 in SMR and 192 of
      1100 in AF. Additional qualitative and quantitative analysis highlighted 44
      biological processes over-represented in our samples compared to the Mus musculus
      gene database. In particular, it was possible to identify proteins implicated in
      the cell cycle, calcium ion binding and glycolysis, with specific expressions and
      abundance, throughout in vitro follicle development. LARGE SCALE DATA: Data are
      available via ProteomeXchange with identifier PXD006227. LIMITATIONS, REASONS FOR
      CAUTION: The proteome analyses described in this study were performed after in
      vitro development. Despite fractionation of the samples before LC-MS/MS,
      proteomic approaches are not exhaustive, thus proteins that are not identified in
      a group are not necessarily absent from that group, although they are likely to
      be less abundant. WIDER IMPLICATIONS OF THE FINDINGS: This study allowed a
      general view of proteins implicated in follicle development in vitro and it
      represents the most complete catalog of the whole follicle proteome available so
      far. Not only were well known proteins of the oocyte identified but also proteins
      that are probably expressed only in granulosa cells. STUDY FUNDING/COMPETING
      INTEREST(S): This study was supported by the Portuguese Foundation for Science
      and Technology, FCT (PhD fellowship SFRH/BD/65299/2009 to A.A.), the Swedish
      Childhood Cancer Foundation (PR 2014-0144 to K.A.R-.W.) and Stockholm County
      Council to K.A.R-.W. The authors of the study have no conflict of interest to
      report.

PMID- 29069486
TI  - ATMOSPHERIC PARTICULATE AND XENON RADIOISOTOPES MONITORING OVER CANADA AND HEALTH
      IMPACT ESTIMATION BEFORE AND AFTER THE FUKUSHIMA NUCLEAR ACCIDENT.
AB  - This article presents the results of atmospheric radioactivity monitoring
      obtained by three Canadian radiation monitoring stations before, after and during
      Fukushima-Daiichi accident. It includes 210Pb, 212Pb and 7Be (naturally occurring
      radionuclides) and 131I, 132I, 129Te, 129mTe, 132Te, 134Cs, 136Cs, 137Cs and
      133Xe (Fukushima contaminants). The maximum activity concentrations were in range
      of 2.3-3.7 Bq/m3 for 133Xe; 2.0-4.4 mBq/m3 for 131I in aerosol form; 0.27-0.83
      mBq/m3 for 137Cs depending on monitoring locations. The effective inhalation and
      cloudshine dose due to the Fukushima contaminants for an adult was estimated in
      range of 0.8-1.1 * 10-4 mSv, out of which the proportions of 133Xe and 131I were
      in range of 64-83% and 15-33%, respectively. During this period, the dose
      resulting from exposure to naturally occurring radionuclides was estimated in
      range of 0.60-1.8 * 10-3 mSv, one order of magnitude higher than those of the
      Fukushima contaminants. The dose impact from exposure to the Fukushima
      contaminants was negligible.

PMID- 29069487
TI  - NF-kappaB1/IKKepsilon Gene Expression and Clinical Activity in Patients With
      Rheumatoid Arthritis.
AB  - Objective: Rheumatoid arthritis (RA) is a systemic and autoimmune disorder whose
      primary characteristic is the chronic inflammation of joints. The objective of
      this study was to evaluate whether there was an association between nuclear
      factor kappa beta1/IKK epsilon (NF-kappaB1/IKKepsilon) gene expression and
      clinical activity in RA. Methods: Sixty patients with RA were included in the
      study: 30 with clinical activity and 30 with clinical remission. NF
      kappaB1/IKKepsilon gene expression was performed by real-time quantitative
      polymerase chain reaction through relative quantification with Taqman probes. A
      ROC curve for NF-kappaB1 and IKKepsilon was also constructed. Results: There were
      significant differences in NF-kappaB1 and IKKepsilon gene expression (P <= .001
      and P <= .029, respectively) between RA patients with clinical activity and
      clinical remission. The multivariate lineal general model showed that the use of
      nonsteroidal anti-inflammatory drugs influenced the NF-kappaB1 (P = .046) and
      IKKepsilon (P = .005) expression. The ROC curves for the event "clinical
      activity" showed the greater area under the curve for NF-kappaB1 (0.827, 95% CI
      0.717-0.937), P <= .001. Conclusion: Although the use of NSAIDs influences the NF
      kappaB1/IKKepsilon pathway, the IKKepsilon expression might be a useful
      laboratorial analysis to evaluate the RA clinical activity.

PMID- 29069488
TI  - Triple-element compound-specific stable isotope analysis of 1,2-dichloroethane
      for characterization of the underlying dehalogenation reaction in two
      Dehalococcoides mccartyi strains.
AB  - Chlorinated ethanes belong to the most common groundwater and soil contaminants.
      Of these, 1,2-dichloroethane (1,2-DCA) is a man-made, persistent and toxic
      contaminant, released due to improper waste treatment at versatile production
      sites. This study investigated the anaerobic transformation of 1,2-DCA by
      Dehalococcoides mccartyi strain 195 and strain BTF08 using triple-element
      compound-specific stable isotope analysis of carbon, chlorine and hydrogen for
      the first time. Isotope fractionation patterns for carbon (epsilonCBTF08 = -28.4
      +/- 3.70/00; epsilonC195 = -30.9 +/- 3.60/00) and chlorine (epsilonClBTF08 = -4.6
      +/- 0.70/00; epsilonCl195 = -4.2 +/- 0.50/00) within both investigated D.
      mccartyi strains, as well as the dual-element analysis (LambdaBTF08 = 6.9 +/-
      1.2; Lambda195 = 7.1 +/- 0.2), supported identical reaction mechanisms for
      dehalogenation of 1,2-DCA. Hydrogen isotope fractionation analysis revealed
      dihaloelimination as prevalent reaction mechanism. Vinyl chloride as major
      intermediate could be excluded by performing the experiment in deuterated aqueous
      media. Furthermore, evaluation of the derived apparent kinetic isotope effects
      (AKIECBTF08 = 1.029/AKIEC195 = 1.031; AKIEClBTF08 = 1.005/AKIECl195 = 1.004)
      pointed towards simultaneous abstraction of both involved chlorine-substituents
      in a concerted matter. It was shown that D. mccartyi strain BTF08 and strain 195
      are capable of complete, direct dihaloelimination of 1,2-DCA to ethene.

PMID- 29069482
TI  - Metals in fungal virulence.
AB  - Metals are essential for life, and they play a central role in the struggle
      between infecting microbes and their hosts. In fact, an important aspect of
      microbial pathogenesis is the 'nutritional immunity', in which metals are
      actively restricted (or, in an extended definition of the term, locally enriched)
      by the host to hinder microbial growth and virulence. Consequently, fungi have
      evolved often complex regulatory networks, uptake and detoxification systems for
      essential metals such as iron, zinc, copper, nickel and manganese. These systems
      often differ fundamentally from their bacterial counterparts, but even within the
      fungal pathogens we can find common and unique solutions to maintain metal
      homeostasis. Thus, we here compare the common and species-specific mechanisms
      used for different metals among different fungal species-focusing on important
      human pathogens such as Candida albicans, Aspergillus fumigatus or Cryptococcus
      neoformans, but also looking at model fungi such as Saccharomyces cerevisiae or
      A. nidulans as well-studied examples for the underlying principles. These direct
      comparisons of our current knowledge reveal that we have a good understanding how
      model fungal pathogens take up iron or zinc, but that much is still to learn
      about other metals and specific adaptations of individual species-not the least
      to exploit this knowledge for new antifungal strategies.

PMID- 29069489
TI  - Editor's Highlight: Effects of Intraperitoneal Injection of SnS2 Flowers on Mouse
      Testicle.
AB  - SnS2 nanoflowers (SnS2 NFs) have been widely used in photoelectric and catalytic
      applications. However, its explosure and reproductive toxicity is unknown. The
      aim of this study was to investigate the effect of exposure to 3 different sized
      SnS2 flowers (dose: 38 mg/kg; size: 50, 80, and 200 nm) in testes of mice for 4
      weeks by intraperitoneal injection. Though the body weight of mice treated or not
      with SnS2 NFs was not different, and SnS2 NFs were distributed to the organs
      including liver, kidney, spleen, heart, brain, and testis, more distribution SnS2
      NFs (50 and 80 nm) were found in testicle tissues compared with SnS2 flowers (200
      nm) in those tissues. The results of sperm count and survival analysis,
      histopathological evaluation, and qRT-PCR detection showed that there was
      moderate reproductive toxicity induced by the small-sized SnS2 NFs in testicle
      tissues. Furthermore, elevated malondialdehyde level and decreased superoxide
      dismutase activity were also observed in the SnS2 NFs (dose: 38 mg/kg; size: 50
      and 80 nm) treated groups. Likewise, the qRT-PCR data indicated that SnS2 NFs can
      induce apoptosis and inflammation responses. Although the pro-inflammation marker
      of TNF-alpha, IL-1beta, iNOS, and COX-2 at the mRNA levels were higher expression
      in 50 and 80 nm groups than that in control and 200 nm group, no statistical
      significance existed between 50 and 80 nm groups. Accordingly, the repeated-dose
      toxicity of SnS2 NFs in testicle tissues was also observed in a dose-dependent
      manner by intraperitoneal injection of SnS2 NFs (size: 50 nm; 0.38, 3.8, and 38
      mg/kg) for 4 weeks, when determined by sperm count, survival rate, and qRT-PCR
      analysis. In addition, transmission electron microscopy showed that the
      ultrastructural abnormalities formed by the small-sized SnS2 NFs in testes were
      more severe than those formed by the large-sized SnS2 in testes. Taken together,
      these findings implied that the SnS2 NFs activated inflammation responses that
      signified apoptosis in murine testes. This study provided useful information for
      risk analysis and regulation of SnS2 NFs by administration agencies.

PMID- 29069490
TI  - Optimizing MSLT Specificity in Narcolepsy With Cataplexy.
AB  - Study Objectives: Multiple sleep onset rapid eye movement (R) periods (SOREMPs)
      and a mean sleep latency of <=8 minutes on the multiple sleep latency test (MSLT)
      are diagnostic criteria of narcolepsy (NC), but also occur in other conditions
      with increased sleep pressure, including insufficient sleep syndrome (ISS), sleep
      disordered breathing (SDB), or Parkinson's disease (PD). These false positives
      are common, may create diagnostic uncertainty, and highlight the need for
      complementary MSLT measures with high specificity for NC. Methods: Detailed
      analysis of MSLT findings in 56 NC, 83 PD, 89 SDB, and 23 ISS patients, using
      receiver operating characteristic curves. Results: A positive MSLT (mean sleep
      latency <= 8.0 minutes and >=2 SOREMPs) was found in 53 NC (95%), 1 PD (1%), 8
      SDB (9%), and 12 ISS patients (52%). MSLT-based differentiation between NC and
      non-NC patients was best when applying a mean R latency of <=5 minutes
      (sensitivity/specificity/positive predictive value [PPV]: 49%/95%/96%) or a mean
      percentage of sleep stage R >= 40% (sensitivity/specificity/PPV: 60%/100%/100%)
      as cutoffs. When analyzing all 252 naps with SOREMPs in isolation, the
      combination of both R latency of <=5 minutes and R percentage of >=50% yielded a
      sensitivity/specificity/PPV of 50%/99%/99%. In addition, a sleep stage sequence
      with R occurring prior to N2 was more common in NC than in non-NC (71% vs. 32%, p
      < .001), and in combination with R percentage of >=50% yielded a
      sensitivity/specificity/PPV of 53%/96%/97%. Conclusions: A better
      characterization of R sleep by latency, duration, and sleep stage sequence
      facilitates detection of false positives and, hence, contributes to a higher MSLT
      specificity in NC.

PMID- 29069491
TI  - A REVIEW ON VARIATION OF NATURAL RADIOACTIVITY ALONG THE SOUTHEAST COAST OF TAMIL
      NADU FOR THE PAST 4 DECADES (1974-2016).
AB  - This review deals with natural radioactivity variation along the southeast coast
      of Tamil Nadu for the past four decades (1974-2016). About 40 research works have
      been conducted along the coast since 1974 in various environmental matrices using
      a variety of experimental methods. For these measurements researchers are adopted
      different experimental methods. The measured gamma dose rate ranged from 30 to
      8700 nGy/h. The mean specific activity of 238U, 232Th and 40K was found to be
      58.8 +/- 28.7, 465.2 +/- 147.3 and 311.2 +/- 27.8 Bq/kg, respectively. The
      calculated annual exposure rate ranged from 0.29 to 12.8 mSv/y with the mean
      value of 3.7 mSv/y which is above the global average of 2.4 mSv/y as reported by
      United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)
      (Report to General Assembly, Annex B Exposures of the public and workers from
      various sources of radiation. United Nations, New York (2008)). Plant food items
      recorded low 210Po activities as compared to seafood organisms. Grain size,
      season and place of sampling have a decisive bearing on coastal radioactivity.
      Therefore, it is concluded from the review data that there is an appreciable
      elevation in background radiation level in the coastal region. This review
      suggests that new radiological surveys using improved methodology that cover the
      entire coastal stretch are needed.

PMID- 29069492
TI  - Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its
      carbohydrate-binding sites.
AB  - Zymogen granule protein 16 (ZG16p) is a soluble lectin that binds to both mannose
      and heparin/heparan sulfate. It is highly expressed in the human digestive tract
      and is secreted into the mucus. In this study, we investigated the effect of
      ZG16p on the proliferation of human colorectal cancer cells. Overexpression of
      ZG16p in Caco-2 cells decreased cell growth. Recombinant ZG16p markedly inhibited
      proliferation of Caco-2, LS174T, HCT116 and HCT15 cells. Caco-2 cell growth was
      not inhibited by two mutated ZG16p proteins, D151A and M5 (K36A, R37A, R53A, R55A
      and R79A) lacking mannose- and heparin-binding activities, respectively.
      Immunofluorescent cell staining revealed that ZG16p-D151A maintained its binding
      to the Caco-2 cell surface, whereas ZG16p-M5 failed to bind to the cells. These
      results suggest that ZG16p interacts with the cell surface via basic amino acids
      substituted in ZG16p-M5 and inhibits Caco-2 cell proliferation via Asp151. In
      addition, growth of patient-derived colorectal tumor organoids in a 3D intestinal
      stem cell system was suppressed by ZG16p but not by ZG16p-M5. Taken together, our
      findings indicate that ZG16p inhibits the growth of colorectal cancer cells via
      its carbohydrate-binding sites in vitro and ex vivo. In this study, a novel
      pathway in cancer cell growth regulation through cell surface carbohydrate chains
      is suggested.

PMID- 29069495
TI  - LETTER TO THE EDITOR: POTENTIAL EFFECTS OF DIAGNOSTIC IRRADIATION FROM COMPUTED
      TOMOGRAPHY ON REPRODUCTIVE SYSTEM AND GENERAL PROTECTIVE STRATEGIES.

PMID- 29069494
TI  - The first near-complete assembly of the hexaploid bread wheat genome, Triticum
      aestivum.
AB  - Common bread wheat, Triticum aestivum, has one of the most complex genomes known
      to science, with 6 copies of each chromosome, enormous numbers of near-identical
      sequences scattered throughout, and an overall haploid size of more than 15
      billion bases. Multiple past attempts to assemble the genome have produced
      assemblies that were well short of the estimated genome size. Here we report the
      first near-complete assembly of T. aestivum, using deep sequencing coverage from
      a combination of short Illumina reads and very long Pacific Biosciences reads.
      The final assembly contains 15 344 693 583 bases and has a weighted average (N50)
      contig size of 232 659 bases. This represents by far the most complete and
      contiguous assembly of the wheat genome to date, providing a strong foundation
      for future genetic studies of this important food crop. We also report how we
      used the recently published genome of Aegilops tauschii, the diploid ancestor of
      the wheat D genome, to identify 4 179 762 575 bp of T. aestivum that correspond
      to its D genome components.

PMID- 29069493
TI  - Horizontal Transfer of Non-LTR Retrotransposons from Arthropods to Flowering
      Plants.
AB  - Even though lateral movements of transposons across families and even phyla
      within multicellular eukaryotic kingdoms have been found, little is known about
      transposon transfer between the kingdoms Animalia and Plantae. We discovered a
      novel non-LTR retrotransposon, AdLINE3, in a wild peanut species. Sequence
      comparisons and phylogenetic analyses indicated that AdLINE3 is a member of the
      RTE clade, originally identified in a nematode and rarely reported in plants. We
      identified RTE elements in 82 plants, spanning angiosperms to algae, including
      recently active elements in some flowering plants. RTE elements in flowering
      plants were likely derived from a single family we refer to as An-RTE.
      Interestingly, An-RTEs show significant DNA sequence identity with non-LTR
      retroelements from 42 animals belonging to four phyla. Moreover, the sequence
      identity of RTEs between two arthropods and two plants was higher than that of
      homologous genes. Phylogenetic and evolutionary analyses of RTEs from both
      animals and plants suggest that the An-RTE family was likely transferred
      horizontally into angiosperms from an ancient aphid(s) or ancestral arthropod(s).
      Notably, some An-RTEs were recruited as coding sequences of functional genes
      participating in metabolic or other biochemical processes in plants. This is the
      first potential example of horizontal transfer of transposons between animals and
      flowering plants. Our findings help to understand exchanges of genetic material
      between the kingdom Animalia and Plantae and suggest arthropods likely impacted
      on plant genome evolution.

PMID- 29069496
TI  - Interim outcomes of delamanid for the treatment of MDR- and XDR-TB in South
      Korea.
AB  - Objectives: Delamanid is a new anti-TB drug, but few data exist on its use
      outside clinical trials. The purpose of this study was to evaluate the efficacy
      as well as the safety and tolerability of a delamanid-containing regimen for 24
      weeks in the treatment of MDR- and XDR-TB. Methods: We performed a retrospective
      cohort study among patients with MDR/XDR-TB who were treated with a delamanid
      containing regimen in seven hospitals in South Korea. Results: A total of 32
      patients with MDR-TB, of which 6 (18.8%) were XDR-TB, were included and all
      completed 24 weeks of delamanid treatment. Of 19 patients (59.4%) who had
      positive culture sputum at the initiation of delamanid treatment, the proportion
      of culture conversion at 8 weeks was 72.2% (13 of 18) in solid medium and 50.0%
      (7 of 14) in liquid medium. The proportion of culture conversion at 24 weeks was
      94.4% (17 of 18) in solid medium and 92.9% (13 of 14) in liquid medium. The
      median time to culture conversion was 33 days (range = 5-81) using solid medium
      and 57 days (range = 8-96) using liquid medium. Of the 32 patients, there was no
      serious adverse event or death. Three patients developed a transient QTcF of >
      500 ms. Conclusions: The use of delamanid combined with optimized background
      regimens has the potential to achieve high culture conversion rates at 24 weeks
      with an acceptable safety and tolerability profile in patients with MDR/XDR-TB.

PMID- 29069497
TI  - From the Cover: Harmane-Induced Selective Dopaminergic Neurotoxicity in
      Caenorhabditis elegans.
AB  - Parkinson's disease (PD) is a debilitating neurodegenerative disease. Although
      numerous exposures have been linked to PD etiology, causative factors for most
      cases remain largely unknown. Emerging data on the neurotoxicity of heterocyclic
      amines suggest that this class of compounds should be examined for relevance to
      PD. Here, using Caenorhabditis elegans as a model system, we tested whether
      harmane exposure produced selective toxicity to dopamine neurons that is
      potentially relevant to PD. Harmane is a known tremorigenic beta-carboline (a
      type of heterocyclic amine) found in cooked meat, roasted coffee beans, and
      tobacco. Thus, this compound represents a potentially important exposure. In the
      nematode model, we observed dopaminergic neurons to be selectively vulnerable,
      showing significant loss in terms of structure and function at lower doses than
      other neuronal populations. In examining mechanisms of toxicity, we observed
      significant harmane-induced decreases in mitochondrial viability and increased
      reactive oxygen species levels. Blocking transport through the dopamine
      transporter (DAT) was not neuroprotective, suggesting that harmane is unlikely to
      enter the cell through DAT. However, a mitochondrial complex I activator did
      partially ameliorate neurodegeneration. Further, mitochondrial complex I
      activator treatment reduced harmane-induced dopamine depletion, measured by the 1
      nonanol assay. In summary, we have shown that harmane exposure in C. elegans
      produces selective dopaminergic neurotoxicity that may bear relevance to PD, and
      that neurotoxicity may be mediated through mitochondrial mechanisms.

PMID- 29069498
TI  - Transient Changes in Hepatic Physiology That Alter Bilirubin and Bile Acid
      Transport May Explain Elevations in Liver Chemistries Observed in Clinical Trials
      of GGF2 (Cimaglermin Alfa).
AB  - GGF2 is a recombinant human neuregulin-1beta in development for chronic heart
      failure. Phase 1 clinical trials of GGF2 were put on hold when transient
      elevations in serum aminotransferases and total bilirubin were observed in 2 of
      43 subjects who received single doses of GGF2 at 1.5 or 0.378 mg/kg. However,
      aminotransferase elevations were modest and not typical of liver injury
      sufficient to result in elevated serum bilirubin. Cynomolgus monkeys administered
      a single 15 mg/kg dose of GGF2 had similar transient elevations in serum
      aminotransferases and bilirubin as well as transient elevations in serum bile
      acids. However, no hepatocellular necrosis was observed in liver biopsies
      obtained during peak elevations. When sandwich-cultured human hepatocytes were
      treated with GGF2 for up to 72 h at concentrations approximately 0.8-fold average
      plasma Cmax for the 0.378 mg/kg dose, no cytotoxicity was observed. Gene
      expression profiling identified approximately 50% reductions in mRNAs coding for
      bilirubin transporters and bile acid conjugating enzymes, as well as changes in
      expression of additional genes mimicking the interleukin-6-mediated acute phase
      response. Similar gene expression changes were observed in GGF2-treated HepG2
      cells and primary monkey hepatocytes. Additional studies conducted in sandwich
      cultured human hepatocytes revealed a transient and GGF2 concentration-dependent
      decrease in hepatocyte bile acid content and biliary clearance of taurocholate
      without affecting biliary taurocholate efflux. Taken together, these data suggest
      that GGF2 does not cause significant hepatocellular death, but transiently
      modifies hepatic handling of bilirubin and bile acids, effects that may account
      for the elevations in serum bilirubin observed in the clinical trial subjects.

PMID- 29069499
TI  - Biogenesis and iron-dependency of ribosomal RNA hydroxylation.
AB  - Post-transcriptional modifications of ribosomal RNAs (rRNAs) are involved in
      ribosome biogenesis and fine-tuning of translation. 5-Hydroxycytidine (ho5C), a
      modification of unknown biogenesis and function, is present at position 2501 of
      Escherichia coli 23S rRNA. We conducted a genome-wide screen in E. coli to
      identify genes required for ho5C2501 formation, and found a previously
      uncharacterized gene, ydcP (renamed rlhA), iron-sulfur cluster (isc) genes, and a
      series of genes responsible for prephenate biosynthesis, indicating that iron
      sulfur clusters and prephenate are required for ho5C2501 formation. RlhA
      interacted with precursors of the 50S ribosomal subunit, suggesting that this
      protein is directly involved in formation of ho5C2501. RlhA belongs to a family
      of enzymes with an uncharacterized peptidase U32 motif and conserved Cys residues
      in the C-terminal region. These elements were essential for ho5C2501 formation.
      We also found that the frequency of ho5C2501 is modulated by environmental iron
      concentration. Together, our results reveal a novel biosynthetic pathway for RNA
      hydroxylation and its response to iron.

PMID- 29069500
TI  - sRNAnalyzer-a flexible and customizable small RNA sequencing data analysis
      pipeline.
AB  - Although many tools have been developed to analyze small RNA sequencing (sRNA
      Seq) data, it remains challenging to accurately analyze the small RNA population,
      mainly due to multiple sequence ID assignment caused by short read length.
      Additional issues in small RNA analysis include low consistency of microRNA
      (miRNA) measurement results across different platforms, miRNA mapping associated
      with miRNA sequence variation (isomiR) and RNA editing, and the origin of those
      unmapped reads after screening against all endogenous reference sequence
      databases. To address these issues, we built a comprehensive and customizable
      sRNA-Seq data analysis pipeline-sRNAnalyzer, which enables: (i) comprehensive
      miRNA profiling strategies to better handle isomiRs and summarization based on
      each nucleotide position to detect potential SNPs in miRNAs, (ii) different
      sequence mapping result assignment approaches to simulate results from
      microarray/qRT-PCR platforms and a local probabilistic model to assign mapping
      results to the most-likely IDs, (iii) comprehensive ribosomal RNA filtering for
      accurate mapping of exogenous RNAs and summarization based on taxonomy
      annotation. We evaluated our pipeline on both artificial samples (including
      synthetic miRNA and Escherichia coli cultures) and biological samples (human
      tissue and plasma). sRNAnalyzer is implemented in Perl and available at:
      http://srnanalyzer.systemsbiology.net/.

PMID- 29069501
TI  - jMorp: Japanese Multi Omics Reference Panel.
AB  - We developed jMorp, a new database containing metabolome and proteome data for
      plasma obtained from >5000 healthy Japanese volunteers from the Tohoku Medical
      Megabank Cohort Study, which is available at https://jmorp.megabank.tohoku.ac.jp.
      Metabolome data were measured by proton nuclear magnetic resonance (NMR) and
      liquid chromatography-mass spectrometry (LC-MS), while proteome data were
      obtained by nanoLC-MS. We released the concentration distributions of 37
      metabolites identified by NMR, distributions of peak intensities of 257
      characterized metabolites by LC-MS, and observed frequencies of 256 abundant
      proteins. Additionally, correlation networks for the metabolites can be observed
      using an interactive network viewer. Compared with some existing databases, jMorp
      has some unique features: (i) Metabolome data were obtained using a single
      protocol in a single institute, ensuring that measurement biases were
      significantly minimized; (ii) The database contains large-scale data for healthy
      volunteers with various health records and genome data and (iii) Correlations
      between metabolites can be easily observed using the graphical viewer.
      Metabolites data are becoming important intermediate markers for evaluating the
      health states of humans, and thus jMorp is an outstanding resource for a wide
      range of researchers, particularly those in the fields of medical science,
      applied molecular biology, and biochemistry.

PMID- 29069502
TI  - Predicting prognosis of short survival time after palliative whole-brain
      radiotherapy.
AB  - Using existing prognostic models, including the Graded Prognostic Assessment
      (GPA), it is difficult to identify patients with brain metastases (BMs) who are
      not likely to survive 2 months after whole-brain radiotherapy (WBRT). The purpose
      of this study was to identify a subgroup of patients who would not benefit
      clinically from WBRT. We retrospectively reviewed the records of 111 patients
      with BMs who were ineligible for surgery or stereotactic irradiation and who
      underwent WBRT between March 2013 and April 2016. Most patients were scheduled to
      receive a total dose of 30 Gy in 10 fractions. Non-small cell lung cancer
      represented the most common primary cancer type (67%), followed by breast cancer
      (12%). Median survival time (MST) was 109 days (range, 4-883). Univariate
      analysis identified five factors significantly associated with poor prognosis:
      performance status (PS) 2-4, perilesional edema, elevated serum lactate
      dehydrogenase (LDH), using steroids during WBRT, and presence of hepatic
      metastases. Multivariate analysis confirmed elevated LDH (>300 IU/l) as an
      independent predictor. MST for LDH >300 IU/l (n = 30) and LDH <=300 IU/L (n = 87)
      cohorts were 47 days and 148 days, respectively (P < 0.001). MSTs for GPA 0-1
      patients (n = 85) with and without elevated LDH were 37 days and 123 days,
      respectively (P < 0.001). More than half of the patients with GPA 0-1 and
      elevated LDH died within two months. Adding elevated LDH to the GPA will permit
      identification of patients with BMs who have extremely unfavorable prognoses.

PMID- 29069503
TI  - Metabolomics as a tool to identify biomarkers to predict and improve outcomes in
      reproductive medicine: a systematic review.
AB  - BACKGROUND: Infertility is a complex disorder with significant medical,
      psychological and financial consequences for patients. With live-birth rates per
      cycle below 30% and a drive from the Human Fertilisation and Embryology Authority
      (HFEA) to encourage single embryo transfer, there is significant research in
      different areas aiming to improve success rates of fertility treatments. One such
      area is investigating the causes of infertility at a molecular level, and
      metabolomics techniques provide a platform for studying relevant biofluids in the
      reproductive tract. OBJECTIVE AND RATIONALE: The aim of this systematic review is
      to examine the recent findings for the potential application of metabolomics to
      female reproduction, specifically to the metabolomics of follicular fluid (FF),
      embryo culture medium (ECM) and endometrial fluid. To our knowledge no other
      systematic review has investigated this topic. SEARCH METHODS: English peer
      reviewed journals on PubMed, Science Direct, SciFinder, were systematically
      searched for studies investigating metabolomics and the female reproductive tract
      with no time restriction set for publications. Studies were assessed for quality
      using the risk of bias assessment and ROBIN-I. OUTCOMES: There were 21 studies
      that met the inclusion criteria and were included in the systematic review.
      Metabolomic studies have been employed for the compositional analysis of various
      biofluids in the female reproductive tract, including FF, ECM, blastocoele fluid
      and endometrial fluid. There is some weak evidence that metabolomics technologies
      studying ECM might be able to predict the viability of individual embryos and
      implantation rate better than standard embryo morphology, However these data were
      not supported by randomized the controlled trials (RCTs) which showed no evidence
      that using metabolomics is able to improve the most important reproductive
      outcomes, such as clinical pregnancy and live-birth rates. This systematic review
      provides guidance for future metabolomic studies on biofluids of the female
      reproductive tract, with a summary of the current findings, promise and pitfalls
      in metabolomic techniques. The approaches discussed can be adapted by other
      metabolomic studies. WIDER IMPLICATIONS: A range of sophisticated modern
      metabolomic techniques are now more widely available and have been applied to the
      analysis of the female reproductive tract. However, this review has revealed the
      paucity of metabolomic studies in the field of fertility and the inconsistencies
      of findings between different studies, as well as a lack of research examining
      the metabolic effects of various gynecological diseases. By incorporating
      metabolomic technology into an increased number of well designed studies, a much
      greater understanding of infertility at a molecular level could be achieved.
      However, there is currently no evidence for the use of metabolomics in clinical
      practice to improve fertility outcomes.

PMID- 29069506
TI  - 'Irish & Roman Catholic Which Upsets All the People Here': Michael McDonnell and
      British Colonial Justice in Mandatory Palestine, 1927-1936.
AB  - In 1927 Michael McDonnell, a diasporic Irish Catholic, was appointed Mandatory
      Palestine's Chief Justice, being directed to institute firm British-style legal
      judicial foundations for future self-governance. This entailed common, equal
      status for Arab and Jewish Palestinians, implicitly de-privileging the Jewish
      National Home. McDonnell was resisted in this by the British Mandate's Anglo
      Jewish, pro-Zionist Attorney General, Norman Bentwich. McDonnell prevailed but
      only at the cost of being characterized lastingly as a pro-Arab, Catholic anti
      Semite. McDonnell's continuing defence of a supreme, independent judiciary
      antagonized the Palestine Executive of High Commissioner Arthur Wauchope, who
      tried to co-opt rather than subordinate Zionist interests. Consequent frictions
      culminated in 1936 with McDonnell adjudicating against supra-legal British
      repression of Palestine's great Arab rebellion. For this he was dismissed and
      ostracized, subsequently publishing critiques of British policy in fringe right
      wing organs. Yet McDonnell professed explicitly non-racist views, reflecting a
      liberal-minded, constitutional Irish nationalist equation of Palestine with
      Ireland, seeing comparable settler-colonial abuses and native distress as
      remediable only by transcendentally impartial justice. Britain reneging on these
      principles led McDonnell, like those Irish imperial servants noted in India, to
      identify with colonial subjects against colonialism. His case is one of empire as
      a system of domination being challenged from within, although his removal
      foreshadowed emerging imperial counter-insurgency's tendency not only to repress
      subject populations but deny civil-progressive alternatives for managing post
      colonial transition.

PMID- 29069504
TI  - Structural basis for the functional role of the Shu complex in homologous
      recombination.
AB  - The Shu complex, a conserved regulator consisting of Csm2, Psy3, Shu1 and Shu2 in
      budding yeast, plays an important role in the assembly of the Rad51-ssDNA
      filament in homologous recombination. However, the molecular basis for the
      assembly of the Shu complex and its functional role in DNA repair is still
      elusive. Here, we report the crystal structure of the yeast Shu complex,
      revealing that Csm2, Psy3, Shu1 and Shu2 interact with each other in sequence to
      form a V-shape overall structure. Shu1 adopts a structure resembling the ATPase
      core domain of Rad51 and represents a new Rad51 paralog. Shu2 assumes a novel
      structural fold consisting of a conserved zinc-finger containing SWIM domain and
      a small insertion domain. The functional roles of the key residues are validated
      using mutagenesis and in vitro pull-down and in vivo yeast growth studies.
      Structural analysis together with available biological data identifies two
      potential DNA-binding sites, one of which might be responsible for binding the
      ssDNA region of the 3'-overhang DNA and the other for the dsDNA region.
      Collectively, these findings reveal the molecular basis for the assembly of the
      Shu complex and shed new insight on its functional role in homologous
      recombination.

PMID- 29069505
TI  - Lung, Bladder, and Kidney Cancer Mortality 40 Years After Arsenic Exposure
      Reduction.
AB  - Background: Region II in northern Chile (population 442 570) experienced a sudden
      major increase in arsenic water concentrations in 1958 in the main city of
      Antofagasta, followed by a major reduction in exposure when an arsenic removal
      plant was installed in 1970. It provides a unique opportunity to study latency
      effects of exposure to arsenic, and this is the first study with mortality data
      up to 40 years after exposure reduction. Methods: We previously identified high
      mortality rates in Region II up to the year 2000. Here we present rate ratios
      (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and
      with unexposed Region V (population 1 539 852) for all years from 1950 to 2010.
      All statistical tests were one-sided. Results: From 2001 to 2010, comparing
      Region II with the rest of Chile, lung and bladder mortality were still greatly
      elevated (RR = 3.38, 95% confidence interval [CI] = 3.19 to 3.58, P < .001 for
      lung cancer in men; RR = 2.41, 95% CI = 2.20 to 2.64, P < .001 for lung cancer in
      women; RR = 4.79, 95% CI = 4.20 to 5.46, P < .001 for bladder cancer in men; RR =
      6.43, 95% CI = 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer
      mortality was also elevated (RR = 1.75, 95% CI = 1.49 to 2.05, P < .001 for men;
      RR = 2.09, 95% CI = 1.69 to 2.57, P < .001 for women). Earlier short latency
      acute myocardial infarction mortality increases had subsided. Conclusions: Lung,
      bladder, and kidney cancer mortality due to arsenic exposure have very long
      latencies, with increased risks manifesting 40 years after exposure reduction.
      Our findings suggest that arsenic in drinking water may involve one of the
      longest cancer latencies for a human carcinogen.

PMID- 29069509
TI  - Clinical and Antibiotic Management of Urinary Tract Infections Pre- and
      Postimplementation of the CLINITEK AUWi System From Siemens to Screen Out
      Negative Urine Samples Submitted for Culture: A Retrospective Cohort Study.
AB  - Objective: To compare patterns of inpatient and outpatient antibiotic use between
      patients who awaited urine culture results and patients whose urine specimens had
      been submitted for culture and were screened using the CLINITEK AUWi System.
      Methods: This quasi-experimental retrospective cohort study included patient
      records with a urine specimen and hospital admission from 1 month before to 1
      month after implementation of the system. We compared data from the pre- and
      postimplementation groups using the chi2 test or Fisher exact test. Results: A
      similar proportion of patients in the pre- and postimplementation groups were
      prescribed antibiotics (71.2% vs 80.0%; P = .45); the postimplementation group
      had a significantly shorter length of stay in hours (median, 226 vs 123; P =
      .005). The median inpatient antibiotic treatment duration was lower for those in
      the postimplementation group; however, the duration of outpatient antibiotic
      treatment was longer. Conclusion: Our findings suggest that screening specimens
      using the CLINITEK AUWi System may reduce the excess administration of
      antibiotics.

PMID- 29069507
TI  - Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell
      activities in rheumatoid arthritis.
AB  - Objectives: Targeting the granulocyte-macrophage colony-stimulating factor (GM
      CSF) pathway holds great potential in the treatment of inflammatory diseases.
      Mavrilimumab, a human monoclonal GM-CSF receptor-alpha antibody, has demonstrated
      clinical efficacy in RA. Our current study aimed to elucidate mechanisms of
      action and identify peripheral biomarkers associated with therapeutic responses
      of GM-CSF antagonism in RA. Methods: A 24-week placebo (PBO)-controlled trial was
      conducted in 305 RA patients who received mavrilimumab (30, 100 or 150 mg) or PBO
      once every 2 weeks. Serum biomarkers and whole blood gene expression profiles
      were measured by protein immunoassay and whole genome microarray. Results:
      Mavrilimumab treatment induced significant down-regulation of type IV collagen
      formation marker (P4NP 7S), macrophage-derived chemokine (CCL22), IL-2 receptor
      alpha and IL-6 compared with PBO. Both early and sustained reduction of P4NP 7S
      was associated with clinical response to 150 mg mavrilimumab treatment. Gene
      expression analyses demonstrated reduced expression of transcripts enriched in
      macrophage and IL-22/IL-17 signalling pathways after GM-CSF blockade therapy.
      Myeloid and T cell-associated transcripts were suppressed in mavrilimumab-treated
      ACR20 responders but not non-responders. While CCL22 and IL-6 down-regulation may
      reflect a direct effect of GM-CSFR blockade on the production of pro-inflammatory
      mediators by myeloid cells, the suppression of IL-2 receptor alpha and IL-17/IL
      22 associated transcripts suggests an indirect suppressive effect of mavrilimumab
      on T cell activation. Conclusion: Our results demonstrated association of
      peripheral biomarker changes with therapeutic response to mavrilimumab in RA
      patients. The sustained efficacy of mavrilimumab in RA may result from both
      direct effects on myeloid cells and indirect effects on T cell activation after
      GM-CSFR blockade.

PMID- 29069508
TI  - Impaired cortico-limbic functional connectivity in schizophrenia patients during
      emotion processing.
AB  - Functional dysconnection is increasingly recognized as a core pathological
      feature in schizophrenia. Aberrant interactions between regions of the cortico
      limbic circuit may underpin the abnormal emotional processing associated with
      this illness. We used a functional magnetic resonance imaging (fMRI) paradigm
      designed to dissociate the various components of the cortico-limbic circuit (i.e.
      a ventral automatic circuit that is intertwined with a dorsal cognitive circuit),
      in order to explore bottom-up appraisal as well as top-down control during
      emotion processing. In schizophrenia patients compared to healthy controls,
      bottom-up processes were associated with reduced interaction between the amygdala
      and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal
      cortex (DLPFC). Contrariwise, top-down control processes led to stronger
      connectivity between the ventral affective and the dorsal cognitive circuits,
      i.e. heightened interactions between the ventral ACC and the DLPFC as well as
      between dorsal and ventral ACC. These findings offer a comprehensive view of the
      cortico-limbic dysfunction in schizophrenia. They confirm previous results of
      impaired propagation of information between the amygdala and the prefrontal
      cortex and suggest a defective functional segregation in the dorsal cognitive
      part of the cortico-limbic circuit.

PMID- 29069510
TI  - Lnc2Meth: a manually curated database of regulatory relationships between long
      non-coding RNAs and DNA methylation associated with human disease.
AB  - Lnc2Meth (http://www.bio-bigdata.com/Lnc2Meth/), an interactive resource to
      identify regulatory relationships between human long non-coding RNAs (lncRNAs)
      and DNA methylation, is not only a manually curated collection and annotation of
      experimentally supported lncRNAs-DNA methylation associations but also a platform
      that effectively integrates tools for calculating and identifying the
      differentially methylated lncRNAs and protein-coding genes (PCGs) in diverse
      human diseases. The resource provides: (i) advanced search possibilities, e.g.
      retrieval of the database by searching the lncRNA symbol of interest, DNA
      methylation patterns, regulatory mechanisms and disease types; (ii) abundant
      computationally calculated DNA methylation array profiles for the lncRNAs and
      PCGs; (iii) the prognostic values for each hit transcript calculated from the
      patients clinical data; (iv) a genome browser to display the DNA methylation
      landscape of the lncRNA transcripts for a specific type of disease; (v) tools to
      re-annotate probes to lncRNA loci and identify the differential methylation
      patterns for lncRNAs and PCGs with user-supplied external datasets; (vi) an R
      package (LncDM) to complete the differentially methylated lncRNAs identification
      and visualization with local computers. Lnc2Meth provides a timely and valuable
      resource that can be applied to significantly expand our understanding of the
      regulatory relationships between lncRNAs and DNA methylation in various human
      diseases.

PMID- 29069512
TI  - Acute Myeloid Leukemia With a Rare t(7;14)(q21;q32) and Trisomy 4 With Poor
      Clinical Outcome: A Case Report.
AB  - Objectives: Recurrent cytogenetic abnormalities and/or molecular aberrations play
      an important role in the diagnosis and prognostification of acute myeloid
      leukemia (AML). We describe a case of a 40 year old woman diagnosed with de novo
      AML with a novel t(7;14)(q21,q32) and trisomy 4 with poor clinical outcome.
      Methods: Morphologic, flow cytometry and cytogenetic results of the patient's
      peripheral blood and bone marrow samples were analyzed. Results: The diagnostic
      bone marrow was hypercellular for age (>95%) with increased blasts (62%) that by
      flow cytometry exhibited myeloid differentiation with a few T/NK lineage markers.
      Cytogenetics showed a t(7;14)(q21,q32) and trisomy 4. The patient had extremely
      poor response to two rounds of induction chemotherapy with persistent leukemia
      following therapy. Conclusion: To the best of our knowledge, the t(7;14) is a
      novel cytogenetic abnormality that has not been reported previously in acute
      myeloid leukemia, and is important to report as it appears to be associated with
      poor prognosis.

PMID- 29069511
TI  - Negative Symptom Interventions in Youth at Risk of Psychosis: A Systematic Review
      and Network Meta-analysis.
AB  - Objective: Youth at clinical high risk (CHR) for psychosis often demonstrate
      significant negative symptoms, which have been reported to be predictive of
      conversion to psychosis and a reduced quality of life but treatment options for
      negative symptoms remain inadequate. Therefore, we conducted a systematic review
      and network meta-analysis of all intervention studies examining negative symptom
      outcomes in youth at CHR for psychosis. Method: The authors searched PsycINFO,
      Medline, Embase, CINAHL, and EBM from inception to December 2016. Studies were
      selected if they included any intervention that reported follow-up negative
      symptoms in youth at CHR for psychosis. Treatment comparisons were evaluated
      using both pairwise and network meta-analyses. Due to the differences in negative
      symptom scales the effect sizes were reported as the standardized mean difference
      (SMD). Results: Of 3027 citations, 32 studies met our inclusion criteria,
      including a total of 2463 CHR participants. The null hypothesis was not rejected
      for any of the 11 treatments. N-methyl-D-aspartate-receptor (NMDAR) modulators
      trended toward a significant reduction in negative symptoms compared to placebo
      (SMD = -0.54; 95% CI = -1.09 to 0.02; I2 = 0%, P = .06). In respective order of
      descending effectiveness as per the treatment hierarchy, NMDAR modulators were
      more effective than family therapy, need-based interventions, risperidone,
      amisulpride, cognitive behavioral therapy, omega-3, olanzapine, supportive
      therapy, and integrated psychological interventions. Conclusions: Efficacy and
      effectiveness were not confirmed for any negative symptom treatment. Many studies
      had small samples and the majority were not designed to target negative symptoms.

PMID- 29069513
TI  - A cohort study of comorbidity in patients with granulomatosis with polyangiitis.
AB  - Objectives: To evaluate the associations between granulomatosis with polyangiitis
      (GPA) and a wide range of comorbidities in patients with GPA compared with
      population-based non-vasculitis patients. Methods: Using the UK-based Clinical
      Practice Research Datalink we identified 570 incident patients with GPA in 1990
      2014, and for each case, we selected up to 10 random non-vasculitis patients
      matched for age, sex, practice and years of history before the date of first GPA
      diagnosis. We compared the distribution of 13 pre-existing comorbidities and
      estimated the risk of each incident comorbidity after the cohort entry between
      GPA and non-vasculitis patients. Results: Patients with GPA were more likely to
      have a history of hypothyroidism at their initial diagnosis compared with non
      vasculitis patients. Patients with GPA had increased risk of incident venous
      thromboembolism any time during follow-up compared with non-vasculitis patients,
      particularly during the first 3 years of follow-up: hazard ratio (HR) of 5.24
      (95% CI: 2.83, 9.71). Risks were also increased for hypertension (HR = 2.45, 95%
      CI: 1.84, 3.26), type 2 diabetes (HR = 2.13, 95% CI: 1.36, 3.32), dyslipidaemia
      (HR = 1.98, 95% CI: 1.29, 3.04) and depression (HR = 1.77, 95% CI: 1.10, 2.86)
      among GPA patients during the first 3 years of follow-up, but not after 3 years
      post-diagnosis. Conclusion: Patients with GPA had a higher prevalence of
      hypothyroidism before the initial diagnosis, a strong risk of developing venous
      thromboembolism during follow-up and increased risks of hypertension,
      dyslipidaemia, type 2 diabetes and depression in the first few years after
      diagnosis, compared with non-vasculitis population.

PMID- 29069514
TI  - Multiple RNA structures affect translation initiation and UGA redefinition
      efficiency during synthesis of selenoprotein P.
AB  - Gene-specific expansion of the genetic code allows for UGA codons to specify the
      amino acid selenocysteine (Sec). A striking example of UGA redefinition occurs
      during translation of the mRNA coding for the selenium transport protein,
      selenoprotein P (SELENOP), which in vertebrates may contain up to 22 in-frame UGA
      codons. Sec incorporation at the first and downstream UGA codons occurs with
      variable efficiencies to control synthesis of full-length and truncated SELENOP
      isoforms. To address how the Selenop mRNA can direct dynamic codon redefinition
      in different regions of the same mRNA, we undertook a comprehensive search for
      phylogenetically conserved RNA structures and examined the function of these
      structures using cell-based assays, in vitro translation systems, and in vivo
      ribosome profiling of liver tissue from mice carrying genomic deletions of 3' UTR
      selenocysteine-insertion-sequences (SECIS1 and SECIS2). The data support a novel
      RNA structure near the start codon that impacts translation initiation,
      structures located adjacent to UGA codons, additional coding sequence regions
      necessary for efficient production of full-length SELENOP, and distinct roles for
      SECIS1 and SECIS2 at UGA codons. Our results uncover a remarkable diversity of
      RNA elements conducting multiple occurrences of UGA redefinition to control the
      synthesis of full-length and truncated SELENOP isoforms.

PMID- 29069515
TI  - MICRODOSIMETRIC APPLICATIONS IN PROTON AND HEAVY ION THERAPY USING SILICON
      MICRODOSIMETERS.
AB  - Using the CMRP 'bridge' MU+ probe, microdosimetric measurements were undertaken
      out-of-field using a therapeutic scanning proton pencil beam and in-field using a
      12C ion therapy field. These measurements were undertaken at Mayo Clinic,
      Rochester, USA and at HIMAC, Chiba, Japan, respectively. For a typical proton
      field used in the treatment of deep-seated tumors, we observed dose-equivalent
      values ranging from 0.62 to 0.99 mSv/Gy at locations downstream of the distal
      edge. Lateral measurements at depths close to the entrance and along the SOBP
      plateau were found to reach maximum values of 3.1 mSv/Gy and 5.3 mSv/Gy at 10 mm
      from the field edge, respectively, and decreased to ~0.04 mSv/Gy 120 mm from the
      field edge. The ability to measure the dose-equivalent with high spatial
      resolution is particularly relevant to healthy tissue dose calculations in hadron
      therapy treatments. We have also shown qualitatively and quantitively the effects
      critical organ motion would have in treatment using microdosimetric spectra.
      Large differences in spectra and RBE10 were observed for treatments where
      miscalculations of 12C ion range would result in critical structures being
      irradiated, showing the importance of motion management.

PMID- 29069516
TI  - Conserved structures formed by heterogeneous RNA sequences drive silencing of an
      inflammation responsive post-transcriptional operon.
AB  - RNA-protein interactions with physiological outcomes usually rely on conserved
      sequences within the RNA element. By contrast, activity of the diverse gamma
      interferon-activated inhibitor of translation (GAIT)-elements relies on the
      conserved RNA folding motifs rather than the conserved sequence motifs. These
      elements drive the translational silencing of a group of chemokine (CC/CXC) and
      chemokine receptor (CCR) mRNAs, thereby helping to resolve physiological
      inflammation. Despite sequence dissimilarity, these RNA elements adopt common
      secondary structures (as revealed by 2D-1H NMR spectroscopy), providing a basis
      for their interaction with the RNA-binding GAIT complex. However, many of these
      elements (e.g. those derived from CCL22, CXCL13, CCR4 and ceruloplasmin (Cp)
      mRNAs) have substantially different affinities for GAIT complex binding.
      Toeprinting analysis shows that different positions within the overall conserved
      GAIT element structure contribute to differential affinities of the GAIT protein
      complex towards the elements. Thus, heterogeneity of GAIT elements may provide
      hierarchical fine-tuning of the resolution of inflammation.

PMID- 29069517
TI  - Expanded and updated data and a query pipeline for iBeetle-Base.
AB  - The iBeetle-Base provides access to sequence and phenotype information for genes
      of the beetle Tribolium castaneum. It has been updated including more and updated
      data and new functions. RNAi phenotypes are now available for >50% of the genes,
      which represents an expansion of 60% compared to the previous version. Gene
      sequence information has been updated based on the new official gene set OGS3 and
      covers all genes. Interoperability with FlyBase has been enhanced: First, gene
      information pages of homologous genes are interlinked between both databases.
      Second, some steps of a new query pipeline allow transforming gene lists from
      either species into lists with related gene IDs, names or GO terms. This
      facilitates the comparative analysis of gene functions between fly and beetle.
      The backend of the pipeline is implemented as endpoints of a RESTful interface,
      such that it can be reused by other projects or tools. A novel online interface
      allows the community to propose GO terms for their gene of interest expanding the
      range of animals where GO terms are defined. iBeetle-Base is available at
      http://ibeetle-base.uni-goettingen.de/.

PMID- 29069518
TI  - Current and emerging therapies in large-vessel vasculitis.
AB  - GCA shares many clinical features with PMR and Takayasu arteritis. The current
      mainstay of therapy for all three conditions is glucocorticoid therapy. Given the
      chronic, relapsing nature of these conditions and the morbidity associated with
      glucocorticoid therapy, there is a need for better treatment options to induce
      and sustain remission with fewer adverse effects. Conventional immunosuppressive
      treatments have been studied and have a modest effect. There is a keen interest
      in biologic therapies with studies showing the efficacy of IL-6 antagonists in
      PMR and GCA. Recently the first two randomized clinical trials in Takayasu
      arteritis have been completed. A major challenge for all of these conditions is
      the lack of standardized measures to assess disease activity. Long-term studies
      are needed to evaluate the impact of biologic therapies showing potential on
      important clinical outcomes such as vascular damage, cost-effectiveness and
      quality of life. The optimal duration of treatment also needs to be assessed.

PMID- 29069522
TI  - Renal replacement modality and stroke risk in end-stage renal disease-a national
      registry study.
AB  - Background: The risk of stroke in end-stage renal disease (ESRD) on renal
      replacement therapy (RRT) is up to 10-fold greater than the general population.
      However, whether this increased risk differs by RRT modality is unclear. Methods:
      We used data contained in the Scottish Renal Registry and the Scottish Stroke
      Care Audit to identify stroke in all adult patients who commenced RRT for ESRD
      from 2005 to 2013. Incidence rate was calculated and regression analyses were
      performed to identify variables associated with stroke. We explored the effect of
      RRT modality at initiation and cumulative dialysis exposure by time-dependent
      regression analysis, using transplant recipients as the reference group. Results:
      A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5%
      were female and 277 patients suffered a stroke (incidence rate was 18.6/1000
      patient-years). Patients who had stroke were older, had higher blood pressure and
      were more likely to be female and have diabetes. On multivariable regression
      older age, female sex, diabetes and higher serum phosphate were associated with
      risk of stroke. RRT modality at initiation was not. On time-dependent analysis,
      haemodialysis (HD) exposure was independently associated with increased risk of
      stroke. Conclusions: In patients with ESRD who initiate RRT, HD use independently
      increases risk of stroke compared with transplantation. Use of peritoneal
      dialysis did not increase risk on adjusted analysis.

PMID- 29069524
TI  - Small but attractive: female-biased nectar production and floral visitors in a
      dimorphic shrub.
AB  - In sexually dimorphic species, hermaphrodite flowers in gynodioecious species or
      male flowers in dioecious species are often larger and produce more nectar than
      their conspecific female flowers. As a consequence, hermaphrodite or male flowers
      frequently receive more pollinator visits. Sex ratio, flower size, floral
      display, nectar production and floral visits were evaluated in two natural
      populations of Fuchsia thymifolia, a morphologically gynodioecious but
      functionally subdioecious insect-pollinated shrub. Sex ratio did not differ from
      the expected 1:1 in the two studied populations. As expected, hermaphrodite
      flowers were larger than female flowers, but in contrast to the general pattern,
      hermaphrodite flowers did not produce nectar or produced much less than female
      flowers. Flower visitors were flies (68%) and bumblebees (24%), both of which
      showed a preference for female flowers. No sex difference was detected in either
      flower longevity or floral display across the flowering season. Higher nectar
      production by females may attract more pollinators, and may be a strategy to
      enhance female reproductive success in this species. Finally, floral dimorphism
      and insect preferences did not seem to hamper the maintenance of sub-dioecy or
      prevent the evolution of dioecy in F. thymifolia.

PMID- 29069527
TI  - Chronobiology comes of age.

PMID- 29069525
TI  - Rapid onset of conjunctivitis associated with overdosing of erlotinib.
AB  - WHAT IS KNOWN AND OBJECTIVE: Erlotinib is one of the epidermal growth factor
      receptor (EGFR) inhibitors and is widely used as a targeted therapy for advanced
      non-small-cell lung cancer (NSCLC). There are a few reports regarding ocular
      adverse effects of erlotinib. Herein, we report a case of rapid onset of ocular
      toxicity associated with overdosing of erlotinib. CASE DESCRIPTION: A 72-year-old
      male with metastatic NSCLC developed conjunctivitis after accidentally taking
      erlotinib at a dosage of 300 mg/day for 4 days. Before that, the patient had been
      taking erlotinib at the prescribed dose of 150 mg/day for 17 days. Erlotinib was
      discontinued for 7 days, and the conjunctivitis was successfully treated
      symptomatically. The adverse effect did not recur when he resumed taking
      erlotinib 150 mg/day, suggesting the ocular change was related to the overdosing
      of erlotinib. WHAT IS NEW AND CONCLUSION: Awareness and close monitoring of this
      adverse effect are helpful for doctors and pharmacists to identify inadvertent
      drug overdose. Patients should be provided comprehensive education before
      receiving targeted therapy.

PMID- 29069520
TI  - RNArchitecture: a database and a classification system of RNA families, with a
      focus on structural information.
AB  - RNArchitecture is a database that provides a comprehensive description of
      relationships between known families of structured non-coding RNAs, with a focus
      on structural similarities. The classification is hierarchical and similar to the
      system used in the SCOP and CATH databases of protein structures. Its central
      level is Family, which builds on the Rfam catalog and gathers closely related
      RNAs. Consensus structures of Families are described with a reduced secondary
      structure representation. Evolutionarily related Families are grouped into
      Superfamilies. Similar structures are further grouped into Architectures. The
      highest level, Class, organizes families into very broad structural categories,
      such as simple or complex structured RNAs. Some groups at different levels of the
      hierarchy are currently labeled as 'unclassified'. The classification is expected
      to evolve as new data become available. For each Family with an experimentally
      determined three-diemsional (3D) structure(s), a representative one is provided.
      RNArchitecture also presents theoretical models of RNA 3D structure and is open
      for submission of structural models by users. Compared to other databases,
      RNArchitecture is unique in its focus on structure-based RNA classification, and
      in providing a platform for storing RNA 3D structure predictions. RNArchitecture
      can be accessed at http://iimcb.genesilico.pl/RNArchitecture/.

PMID- 29069523
TI  - Uncoupling Effect of F16 Is Responsible for Its Mitochondrial Toxicity and
      Anticancer Activity.
AB  - As a novel delocalized lipophilic cation, F16 selectively accumulates in
      mitochondria of carcinoma cells and shows a broad spectrum of antiproliferative
      action towards cancer cell lines. In order to reveal the mode of action and
      molecular mechanism of F16 inducing cytotoxicity, we investigated the effects of
      F16 on cancer cells and isolated mitochondria relative to its precursor compound
      (E)-3-(2-(pyridine-4yl)vinyl)-1 H-indole (PVI), which has a similar structure
      without positive charge. It was found that PVI did not accumulate in
      mitochondria, and exhibited lower cytotoxicity compared to F16. However, when
      they were directly incubated with mitochondria, both F16 and PVI were observed to
      induce damage to mitochondrial structure and function. Moreover, it was found
      that F16 as well as PVI acted as uncouplers on mitochondria, and further rescue
      experiments revealed that the addition of adenosine 5'-triphosphate was the most
      effective way to recover the cell viability decreased by F16. Thus it was
      concluded that the decreased intracellular adenosine 5'-triphosphate availability
      induced by the uncoupling effect of F16 was a major factor in F16-mediated
      cytotoxicity. Futhermore, the results indicated that the uncoupling effect of F16
      is attributed to its chemical stucture in common with PVI but independent of its
      positive charge. The study may shed light on understanding the underlying
      mechanism of action for F16, and providing suggestions for the design of new
      mitochondria-targeted antitumor molecules.

PMID- 29069521
TI  - Love flows downstream: mothers' and children's neural representation similarity
      in perceiving distress of self and family.
AB  - The current study aimed to capture empathy processing in an interpersonal
      context. Mother-adolescent dyads (N = 22) each completed an empathy task during
      fMRI, in which they imagined the target person in distressing scenes as either
      themselves or their family (i.e. child for the mother, mother for the child).
      Using multi-voxel pattern approach, we compared neural pattern similarity for the
      self and family conditions and found that mothers showed greater perceptual
      similarity between self and child in the fusiform face area (FFA), representing
      high self-child overlap, whereas adolescents showed significantly less self
      mother overlap. Adolescents' pattern similarity was dependent upon family
      relationship quality, such that they showed greater self-mother overlap with
      higher relationship quality, whereas mothers' pattern similarity was independent
      of relationship quality. Furthermore, adolescents' perceptual similarity in the
      FFA was associated with increased social brain activation (e.g. temporal parietal
      junction). Mediation analyses indicated that high relationship quality was
      associated with greater social brain activation, which was mediated by greater
      self-mother overlap in the FFA. Our findings suggest that adolescents show more
      distinct neural patterns in perceiving their own vs their mother's distress, and
      such distinction is sensitive to mother-child relationship quality. In contrast,
      mothers' perception for their own and child's distress is highly similar and
      unconditional.

PMID- 29069529
TI  - Improved Free-Energy Landscape Quantification Illustrated with a Computationally
      Designed Protein-Ligand Interaction.
AB  - Quantifying the energy landscape underlying protein-ligand interactions leads to
      an enhanced understanding of molecular recognition. A powerful yet accessible
      single-molecule technique is atomic force microscopy (AFM)-based force
      spectroscopy, which generally yields the zero-force dissociation rate constant
      (koff ) and the distance to the transition state (Deltax? ). Here, we introduce
      an enhanced AFM assay and apply it to probe the computationally designed protein
      DIG10.3 binding to its target ligand, digoxigenin. Enhanced data quality enabled
      an analysis that yielded the height of the transition state (DeltaG? =6.3+/-0.2
      kcal mol-1 ) and the shape of the energy barrier at the transition state (linear
      cubic) in addition to the traditional parameters [koff (=4+/-0.1*10-4  s-1 ) and
      Deltax? (=8.3+/-0.1 A)]. We expect this automated and relatively rapid assay to
      provide a more complete energy landscape description of protein-ligand
      interactions and, more broadly, the diverse systems studied by AFM-based force
      spectroscopy.

PMID- 29069526
TI  - Needs and preferences of patients with head and neck cancer in integrated care.
AB  - OBJECTIVES: Incorporation of patients' perspectives in daily practice is
      necessary to adapt care to users' needs. However, information on patients' needs
      and preferences for integrated care is lacking. The aim was to explore these
      needs and preferences, taking patients with head and neck cancer (HNC) as
      example, to adapt current integrated care to be more patient-centred. DESIGN:
      Semi-structured interviews were held with current and former patients and
      chairmen of patient associations. Relevant needs and preferences were identified
      and categorised using the eight-dimension Picker model of patient-centred care.
      SETTING: Integrated HNC in the Netherlands. PARTICIPANTS: Patients with HNC and
      chairmen of two Dutch HNC patient associations. MAIN OUTCOME MEASURES: Patients'
      needs and preferences of integrated HNC care categorised according the Picker
      model. RESULTS: A total of 34 themes of needs and preferences were identified, by
      14 patients with HNC or their delegates, using the Picker dimensions. Themes
      often emerged were as follows: personalisation of health care regarding patient
      values; clear insight into the healthcare process at organisational level; use of
      personalised communication, education and information that meets patients'
      requirements; adequate involvement of allied health professionals for physical
      support; more attention to the impact of HNC and its treatment; adequate
      involvement of family and friends; adequate general practitioner involvement in
      the aftercare; and waiting time reduction. CONCLUSIONS: Monitoring the identified
      themes in integrated HNC care, fitting in the Picker model, will enable us to
      respond better to the needs and preferences of patients, and patient-centred care
      in oncological care can be enhanced.

PMID- 29069528
TI  - Amphiphilic Polymer-Based Fluorescent Probe for Enantioselective Recognition of
      Amino Acids in Immiscible Water and Organic Phases.
AB  - Atom transfer radical polymerization (ATRP) of N-isopropylacrylamide was
      conducted in the presence of a 3,3'-diformyl-1,1'-BINOL-based diinitiator
      (BINOL=1,1'-bi-2-naphthol) to give polymer (S)-7, which was soluble in both water
      and common organic solvents. Polymer (S)-7 in combination with Zn2+ in aqueous
      solution (BICINE buffer at pH 8.80) showed highly enantioselective fluorescence
      enhancement in the presence of a number of amino acids. It was found that
      chloroform can be used to extract the aqueous polymer-Zn2+ -amino acid solution
      and the resulting chloroform extract maintained the highly enantioselective
      fluorescence response. Thus, the enantiomeric composition of a chiral amino acid
      can be determined in the two immiscible solvents of water and chloroform. The
      aqueous polymer-Zn2+ -amino acid solution showed a lower critical solution
      temperature (LCST) at 34  degrees C, above which the polymer-Zn2+ -amino acid
      adduct precipitated out. Measuring the fluorescence of the precipitate
      redissolved in the aqueous buffer solution showed the retention of the high
      enantioselectivity. Both the chloroform extraction and the thermo-induced
      precipitation have allowed the fluorescence response of the sensor toward amino
      acids to be measured away from the original substrate solution. These two
      strategies should minimize the interference by other reaction components on the
      fluorescence measurement when the sensor is applied to analyze the asymmetric
      reaction screening experiments.

PMID- 29069532
TI  - Robotic vascular ligation, medial to lateral dissection and splenic flexure
      mobilization for rectal cancer - a video vignette.

PMID- 29069519
TI  - Increased rostral anterior cingulate activity following positive mental imagery
      training in healthy older adults.
AB  - The ability to form positive mental images may be an important aspect of mental
      health and well-being. We have previously demonstrated that the vividness of
      positive prospective imagery is increased in healthy older adults following
      positive imagery cognitive training. The rostral anterior cingulate cortex (rACC)
      is involved in the simulation of future affective episodes. Here, we investigate
      the effect of positive imagery training on rACC activity during the imagination
      of novel, ambiguous scenarios vs closely matched control training. Seventy-five
      participants received 4 weeks of positive imagery or control training.
      Participants underwent a functional magnetic resonance imaging scan, during which
      they completed an Ambiguous Sentences Task, which required them to form mental
      images in response to cues describing ambiguous social events. rACC activity was
      positively correlated with the pleasantness ratings of images formed. Positive
      imagery training increased rACC and bilateral hippocampal activity compared with
      the control training. Here, we demonstrate that rACC activity during positive
      imagery can be changed by the cognitive training. This is consistent with other
      evidence that this training enhances the vividness of positive imagery, and
      suggests the training may be acting to increase the intensity and affective
      quality of imagery simulating the future.

PMID- 29069530
TI  - Agronomic and chemical performance of field-grown tobacco engineered for
      triterpene and methylated triterpene metabolism.
AB  - Squalene is a linear intermediate to nearly all classes of triterpenes and
      sterols and is itself highly valued for its use in wide range of industrial
      applications. Another unique linear triterpene is botryococcene and its
      methylated derivatives generated by the alga Botryococcus braunii race B, which
      are progenitors to fossil fuel deposits. Production of these linear triterpenes
      was previously engineered into transgenic tobacco by introducing the key steps of
      triterpene metabolism into the particular subcellular compartments. In this
      study, the agronomic characteristics (height, biomass accumulation, leaf area),
      the photosynthetic capacity (photosynthesis rate, conductance, internal CO2
      levels) and triterpene content of select lines grown under field conditions were
      evaluated for three consecutive growing seasons. We observed that transgenic
      lines targeting enzymes to the chloroplasts accumulated 50-150 times more
      squalene than the lines targeting the enzymes to the cytoplasm, without
      compromising growth or photosynthesis. We also found that the transgenic lines
      directing botryococcene metabolism to the chloroplast accumulated 10- to 33-fold
      greater levels than the lines where the same enzymes were targeted to in the
      cytoplasm. However, growth of these high botryococcene accumulators was highly
      compromised, yet their photosynthesis rates remained unaffected. In addition, in
      the transgenic lines targeting a triterpene methyltransferase (TMT) to the
      chloroplasts of high squalene accumulators, 55%-65% of total squalene was
      methylated, whereas in the lines expressing a TMT in the cytoplasm, only 6%-13%
      of squalene was methylated. The growth of these methylated triterpene
      accumulating lines was more compromised than that of nonmethylated squalene
      lines.

PMID- 29069534
TI  - Developing control algorithms of a voluntary cough for an artificial
      bioengineered larynx using surface electromyography of chest muscles: A
      prospective cohort study.
AB  - OBJECTIVE: This prospective cohort study investigates the prediction of a
      voluntary cough using surface electromyography (EMG) of intercostal and diaphragm
      muscles, to develop control algorithms for an EMG-controlled artificial larynx.
      SETTING: The Ear Institute, London. MAIN OUTCOME MEASURES: Electromyography onset
      compared to voluntary cough exhalation onset and to 100 ms (to give the
      artificial larynx the time to close the bioengineered vocal cords) before
      voluntary cough exhalation onset, in twelve healthy participants. RESULTS: In the
      189 EMG of intercostal muscle-detected voluntary coughs, 172 coughs (91% CI 70
      112) were detected before onset of cough exhalation and 128 coughs (67.6% CI 33.7
      101.7) 100 ms before onset of cough exhalation. In the 158 EMG of diaphragm
      muscle-detected voluntary coughs, 149 coughs (94.3% CI 76.3-112.3) were detected
      before onset of cough exhalation and 102 coughs (64.6% CI 26.6-102.6) 100 ms
      before onset of cough exhalation. More coughs were detected before onset of cough
      exhalation when combining EMG activity of intercostal and diaphragm muscles and
      comparing this to intercostal muscle activity alone (183 coughs [96.8% CI 83.8
      109.8] vs 172 coughs, P = .0294). When comparing the mentioned combination to
      diaphragm muscle activity alone, the higher percentage of detected coughs before
      cough exhalation onset was not found to be significant (183 coughs vs 149 coughs,
      P = .295). In addition, more coughs were detected 100 ms before onset of cough
      exhalation with the mentioned combination of EMG activity and comparing this to
      intercostal muscles alone (149 coughs [78.8% CI 48.8-108.8] vs 128 coughs, P =
      .0198) and to diaphragm muscles alone (149 coughs vs 102 coughs, P = .0038).
      CONCLUSIONS: Most voluntary coughs can be predicted based on combined EMG signals
      of intercostal and diaphragm muscles, and therefore, these two muscle groups will
      be useful in controlling the bioengineered vocal cords within the artificial
      larynx during a voluntary cough.

PMID- 29069531
TI  - Factors associated with the variability of calcineurin inhibitor blood levels in
      kidney recipients grafted for more than 1 year.
AB  - The study of calcineurin inhibitor (CNI) blood level variability to evaluate
      adherence in transplantation has improved over the years. The aim of our study
      was to assess factors associated with this variability using the coefficient of
      variation (CV). A cross-sectional sample of kidney recipients grafted for more
      than 1 year was recruited. We recorded clinical data, data from a clinical
      pharmacist interview and from six questionnaires measuring adherence,
      satisfaction, behaviours, beliefs, perception of the illness and social
      vulnerability. A total of 408 recipients were enrolled (61.2% male, mean age 54)
      and divided into two groups: low variability CV < 30% (n = 302), high variability
      CV >= 30% (n = 106). In univariate analysis, hospital-home distance,
      cyclosporine, time since transplantation and presence of discrepancies in drug
      regimen were associated with a greater risk of CV >= 30%. In contrast, tacrolimus
      QD conferred a lower risk of CV >= 30%. In multivariate analysis, only the
      presence of discrepancies remained significant: (OR 3.2 [1.21-9.01]; P = 0.022).
      Discrepancies in drug regimen appear as the main risk factor associated with CNI
      blood variability. The clinical pharmacist's input is an accurate and simple way
      of detecting non-adherence which is not revealed in self-report questionnaires.

PMID- 29069533
TI  - Dropout rate from the liver transplant waiting list because of hepatocellular
      carcinoma progression in hepatitis C virus-infected patients treated with direct
      acting antivirals.

PMID- 29069535
TI  - Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical
      implications.
AB  - Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific
      antigen receptors and are relatively rare as compared to adaptive lymphocytes.
      ILCs play important roles in allergic and nonallergic inflammatory diseases due
      to their location at barrier surfaces within the airways, gut, and skin, and they
      respond to cytokines produced by activated cells in their local environment.
      Innate lymphoid cells contribute to the immune response by the release of
      cytokines and other mediators, forming a link between innate and adaptive
      immunity. In recent years, these cells have been extensively characterized and
      their role in animal models of disease has been investigated. Data to translate
      the relevance of ILCs in human pathology, and the potential role of ILCs in
      diagnosis, as biomarkers and/or as future treatment targets are also emerging.
      This review, produced by a task force of the Immunology Section of the European
      Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and
      researchers, highlights the role of ILCs in human allergic and nonallergic
      diseases in the airways, gastrointestinal tract, and skin, with a focus on new
      insights into clinical implications, therapeutic options, and future research
      opportunities.

PMID- 29069538
TI  - The Effect of Different Methods of Fermentation on the Detection of Milk Protein
      Residues in Retail Cheese by Enzyme-Linked Immunosorbent Assay (ELISA).
AB  - : Milk and milk products are among the most important allergenic food
      ingredients, both in the United States and throughout the world; cheeses are
      among the most important of these milk products. Milk contains several major
      antigenic proteins, each with differing susceptibilities to proteolytic enzymes.
      The extent of proteolysis in cheese varies as a result of conditions during
      manufacture and ripening. Proteolysis has the potential to degrade antigenic and
      allergenic epitopes that are important for residue detection and elicitation of
      allergic reactions. Commercial enzyme-linked immunosorbent assays (ELISAs) are
      not currently validated for use in detecting residues in hydrolyzed or fermented
      food products. Eighteen retail cheeses produced using 5 different styles of
      fermentation were investigated for detectable milk protein residues with 4
      commercial ELISA kits. Mozzarella, Swiss, Blue, Limburger, and Brie cheeses were
      assessed. The Neogen Veratox(r) Casein and Neogen Veratox(r) Total Milk kits were
      capable of detecting milk residues in most cheeses evaluated, including blue
      veined cheeses that exhibit extensive proteolysis. The other 2 ELISA kits
      evaluated, r-Biopharm(r) Fast Casein and ELISA SystemsTM Casein, can detect milk
      residues in cheeses other than blue-veined varieties. ELISA results cannot be
      quantitatively compared among kits. The quantitative reliability of ELISA results
      in detection of cheese residues is questionable, but some methods are
      sufficiently robust to use as a semi-quantitative indication of proper allergen
      control for the validation of cleaning programs in industry settings. PRACTICAL
      APPLICATION: Many commercially available enzyme-linked immunosorbent assays
      (ELISAs) are not validated for detection of allergenic residues in fermented or
      hydrolyzed products. This research seeks to determine if commercial milk ELISAs
      can detect milk residues in varieties of cheese that have undergone different
      styles of fermentation and different degrees of proteolysis. Only certain milk
      ELISA kits are capable of detecting residues in all varieties of cheese. However,
      commercial milk ELISA kits are capable of semiquantitative detection of cheese
      residues in foods, or in industry settings for the validation of allergen
      cleaning programs.

PMID- 29069536
TI  - Unexpectedly high genetic diversity and divergence among populations of the
      apomictic Neotropical tree Miconia albicans.
AB  - Since tropical trees often have long generation times and relatively small
      reproductive populations, breeding systems and genetic variation are important
      for population viability and have consequences for conservation. Miconia albicans
      is an obligate, diplosporous, apomictic species widespread in the Brazilian
      Cerrado, the savanna areas in central Brazil and elsewhere in the Neotropics. The
      genetic variability would be, theoretically, low within these male-sterile and
      possibly clonal populations, although some variation would be expected due to
      recombination during restitutional meiosis. We used ISSR markers to assess
      genetic diversity of M. albicans and to compare with other tropical trees,
      including invasive species of Melastomataceae. A total of 120 individuals from
      six populations were analysed using ten ISSR primers, which produced 153 fully
      reproducible fragments. The populations of M. albicans presented mean Shannon's
      information index (I) of 0.244 and expected heterozygosity (He ) of 0.168. Only
      two pairs of apparently clonal trees were identified, and genetic diversity was
      relatively high. A hierarchical amova for all ISSR datasets showed that 74% of
      the variance was found among populations, while only 26% of the variance was
      found within populations of this species. Multivariate and Bayesian analyses
      indicated marked separation between the studied populations. The genetic
      diversity generated by restitutional meiosis, polyploidy and possibly other
      genome changes may explain the morpho-physiological plasticity and the ability of
      these plants to differentiate and occupy such a wide territory and different
      environmental conditions. Producing enormous amounts of bird-dispersed fruits, M.
      albicans possess weedy potential that may rival other Melastomataceae alien
      invaders.

PMID- 29069541
TI  - Bimodal Evans-Polanyi Relationships in Dioxirane Oxidations of sp3 C-H: Non
      perfect Synchronization in Generation of Delocalized Radical Intermediates.
AB  - The selectivities in C-H oxidations of a variety of compounds by DMDO have been
      explored with density functional theory. There is a linear Evans-Polanyi-type
      correlation for saturated substrates. Activation energies correlate with reaction
      energies or, equivalently, BDEs (DeltaH?sat = 0.91*BDE - 67.8). Unsaturated
      compounds, such as alkenes, aromatics, and carbonyls, exhibit a different
      correlation for allylic and benzylic C-H bonds (DeltaH?unsat = 0.35*BDE - 13.1).
      Bernasconi's Principle of Non-Perfect Synchronization (NPS) is found to operate
      here. The origins of this phenomenon were analyzed by a Distortion/Interaction
      model. Computations indicate early transition states for H-abstractions from
      allylic and benzylic C-H bonds, but later transition states for the saturated.
      The reactivities are mainly modulated by the distortion energy and the degree of
      dissociation of the C-H bond. While the increase in barrier with higher BDE is
      not unexpected from the Evans-Polanyi relationship, two separate correlations,
      one for saturated compounds, and one for unsaturated leading to delocalized
      radicals, were unexpected.

PMID- 29069537
TI  - THE QUALITY OF FATHER-CHILD ROUGH-AND-TUMBLE PLAY AND TODDLERS' AGGRESSIVE
      BEHAVIOR IN CHINA.
AB  - The purpose of this study was to explore the influence of the quality of early
      father-child rough-and-tumble play (RTP) on toddler aggressive behaviors and more
      fully understand how child, mother, and father characteristics were associated
      with higher quality father-child RTP among contemporary urban Chinese families.
      Participants included 42 families in Changsha, China. Play observations of
      fathers and their children were coded for RTP quality. The specific RTP quality
      of father-child reciprocity of dominance was associated with fewer toddler
      aggressive behaviors, as rated by both fathers and mothers. Mothers' democratic
      parenting attitudes were associated with higher quality father-child RTP. These
      findings suggest that higher quality father-child RTP may be one way in which
      some fathers influence children's expression of aggressive behaviors, and the
      quality of father-child RTP may be influenced by the broader family, social, and
      cultural contexts.

PMID- 29069543
TI  - Complex between Formic Acid and Nitrous Oxide: A Matrix-Isolation and
      Computational Study.
AB  - The complex of formic acid (FA, HCOOH) with nitrous oxide (N2O) was studied
      experimentally and computationally. Eight structures of the trans-FA...N2O
      complex and nine structures of the cis-FA...N2O complex were found at the density
      functional theory (M06-2X and wB97XD), MP2(full), and CCSD(T)-F12a levels. Two
      structures of the trans-FA...N2O complex (1t and 3t) and two structures of the
      cis-FA...N2O complex (1c and 3c) were identified by infrared spectroscopy in an
      argon matrix. Structure 1t with the bonded OH group appears in the matrices after
      deposition. Structures 3t and 3c with the free OH groups were prepared by
      vibrational excitation of the trans-FA conformer in structures 1t and 3t,
      respectively. Structure 3t is thermally unstable and relaxes to structure 1t at
      ~15 K. Structure 1c with the bonded OH group is made by vibrational excitation of
      trans-FA monomer combined with thermal annealing. The lifetimes of the cis
      FA...N2O complex structures 1c (81.5 min) and 3c (18.7 min) in an argon matrix at
      4.3 K are longer than that of cis-FA monomer (6.3 min). This difference agrees
      with the calculated stabilization barriers of these species.

PMID- 29069540
TI  - Methods for Alleviating Stress and Increasing Resilience in the Midwifery
      Community: A Scoping Review of the Literature.
AB  - INTRODUCTION: Work-related stress and exposure to traumatic birth have
      deleterious impacts on midwifery practice, the midwife's physiologic well-being,
      and the midwifery workforce. This is a global phenomenon, and the specific
      sources of this stress vary dependent on practice setting. This scoping review
      aims to determine which, if any, modalities help to reduce stress and increase
      resilience among a population of midwives. METHODS: A scoping review of the
      literature published between January 2011 and September 2016 using PubMed,
      CINAHL, Embase, PsycINFO, and Cochrane databases was performed. Of the initial
      796 reviewed records, 6 met inclusion criteria. RESULTS: Three of the 6 included
      studies were quantitative in nature, 2 were qualitative, and one used mixed
      methods. Countries where studies were conducted include Uganda, Iran, the United
      Kingdom, Israel, and Australia. Three of the studies used interventions for
      stress reduction and increased coping. Two of these 3 used a mindfulness-based
      stress reduction program resulting in improved stress levels and coping skills.
      In each study, midwives express a desire for work-based programs and support from
      colleagues and employers for increasing coping abilities. These studies focused
      on stress reduction and/or increasing resilience. DISCUSSION: While modalities
      such as mindfulness-based stress reduction show promise, further studies with a
      cohort of midwives should be conducted. These studies should include
      interventions aimed at addressing the needs of midwives to improve psychological
      outcomes related to employment-related stress on a global scale and specific to
      each health care context.

PMID- 29069542
TI  - Determination of Enantiomeric Purity of Single-Wall Carbon Nanotubes Using Flavin
      Mononucleotide.
AB  - Although enantiomeric separation of single-wall carbon nanotubes is possible,
      their enantiomeric purity (EP) remains an issue due to a lack of effective
      evaluation methods. In this work, we report the EP of (6,5) carbon nanotube
      enantiomers using flavin mononucleotide (FMN) as an enantiomer-sensitive
      dispersant. The enantiomers (6,5) and (11,-5) were separated by a gel column
      chromatography method and dispersed in a FMN aqueous solution. In these
      solutions, (6,5) and (11,-5) showed E11 optical transitions at different
      wavelengths due to handedness-dependent interactions with the FMN molecule, which
      enabled us to estimate each concentration, namely, the EP. We prepared six
      intermediate-purity enantiomer samples by mixing the (6,5) and (11,-5)
      enantiomers and measured their circular dichroism (CD) spectra. The CD signal was
      confirmed to change linearly with the EP. Using this relationship, we can
      estimate the EP of any mixture of (6,5) and (11,-5) from its CD intensity.

PMID- 29069539
TI  - Low-intensity pulsed ultrasound stimulation for mandibular condyle osteoarthritis
      lesions in rats.
AB  - OBJECTIVE: This study evaluated low-intensity pulsed ultrasound effects for
      temporomandibular joint osteoarthritis in adult rats. MATERIAL AND METHODS:
      Osteoarthritis-like lesions were induced in 24 adult rats' temporomandibular
      joints with low-dose mono-iodoacetate injections. The rats were divided into four
      groups: control and mono-iodoacetate groups, injected with contrast media and
      mono-iodoacetate, respectively, at 12 weeks and observed until 20 weeks; and low
      intensity pulsed ultrasound and mono-iodoacetate + low-intensity pulsed
      ultrasound groups, injected with contrast media and mono-iodoacetate,
      respectively, at 12 weeks with low-intensity pulsed ultrasound performed from 16
      to 20 weeks. Condylar bone mineral density, bone mineral content and bone volume
      were evaluated weekly with microcomputed tomography. Histological and
      immunohistochemical staining for matrix metalloproteinases-13 was performed at 20
      weeks. RESULTS: At 20 weeks, the mono-iodoacetate + low-intensity pulsed
      ultrasound group showed significantly higher bone mineral density, bone mineral
      content and bone volume than the mono-iodoacetate group; however, these values
      remained lower than those in the other two groups. On histological and
      immunohistochemical analysis, the chondrocytes were increased, and fewer matrix
      metalloproteinases-13 immunopositive cells were identified in the mono
      iodoacetate + low-intensity pulsed ultrasound group than mono-iodoacetate group.
      CONCLUSIONS: Low-intensity pulsed ultrasound for 2 weeks may have therapeutic
      potential for treating temporomandibular joint osteoarthritis lesions.

PMID- 29069549
TI  - A case definition for Salmonella Brandenburg infection in dairy heifers.

PMID- 29069551
TI  - How to Think about "Medicare for All".

PMID- 29069546
TI  - Contrasting Photolytic and Thermal Decomposition of Phenyl Azidoformate: The
      Curtius Rearrangement Versus Intramolecular C-H Amination.
AB  - The decomposition of phenyl azidoformate, PhOC(O)N3, was studied by combining
      matrix isolation spectroscopy and quantum chemical calculations. Upon UV laser
      photolysis (193 and 266 nm), the azide isolated in cryogenic noble gas matrices
      (Ne and Ar, 2.8 K) decomposes into N2 and a novel oxycarbonylnitrene PhOC(O)N,
      which was identified by matrix-isolation IR spectroscopy (with 15N labeling) and
      EPR spectroscopy (|D/hc| = 1.620 cm-1 and |E/hc| = 0.024 cm-1). Subsequent
      visible-light irradiation (532 nm) causes rearrangement of the nitrene into
      phenoxy isocyanate PhONCO with complex secondary fragmentation (PhO. + .NCO) and
      radical recombination species in matrices. The observation of PhONCO provides
      solid evidence for the Curtius rearrangement of phenyl azidoformate. In sharp
      contrast, flash vacuum pyrolysis (FVP) of PhOC(O)N3 at 550 K yields N2 and
      exclusively the intramolecular C-H amination product 3H-benzooxazol-2-one. FVP at
      higher temperature (700 K) leads to further dissociation into CO2, HNCO, and ring
      contraction products. To account for the very different photolytic and thermal
      decomposition products, the underlying mechanisms for the Curtius rearrangement
      (concerted and stepwise) of PhOC(O)N3 and the intramolecular C-H amination of the
      nitrene in both singlet and triplet states are discussed with the aid of quantum
      chemical calculations using the B3LYP, CBS-QB3, and CASPT2 methods.

PMID- 29069550
TI  - Is There Merit in Merit Aid?

PMID- 29069545
TI  - Gold Nanoparticles on Functionalized Silicon Substrate under Coulomb Blockade
      Regime: An Experimental and Theoretical Investigation.
AB  - Single charge electronics offer a way for disruptive technology in
      nanoelectronics. Coulomb blockade is a realistic way for controlling the electric
      current through a device with the accuracy of one electron. In such devices the
      current exhibits a step-like increase upon bias which reflects the discrete
      nature of the fundamental charge. We have assembled a double tunnel junction on
      an oxide-free silicon substrate that exhibits Coulomb staircase characteristics
      using gold nanoparticles (AuNPs) as Coulomb islands. The first tunnel junction is
      an insulating layer made of a grafted organic monolayer (GOM) developed for this
      purpose. The GOM also serves for attaching AuNPs covalently. The second tunnel
      junction is made by the tip of an STM. We show that this device exhibits
      reproducible Coulomb blockade I-V curves at 40 K in vacuum. We also show that
      depending on the doping of the silicon substrate, the whole Coulomb staircase can
      be adjusted. We have developed a simulation approach based on the orthodox theory
      that was completed by calculating the bias dependent tunnel barriers and by
      including an accurate calculation of the band bending. This model accounts for
      the experimental data and the doping dependence of Coulomb oscillations. This
      study opens new perspectives toward designing new kind of single electron
      transistors (SET) based on this dependence of the Coulomb staircase with the
      charge carrier concentration.

PMID- 29069544
TI  - Exploiting the Sensitivity of Nutrient Transporter Deletion Strains in Discovery
      of Natural Product Antimetabolites.
AB  - Actinomycete secondary metabolites are a renowned source of antibacterial
      chemical scaffolds. Herein, we present a target-specific approach that increases
      the detection of antimetabolites from natural sources by screening actinomycete
      derived extracts against nutrient transporter deletion strains. On the basis of
      the growth rescue patterns of a collection of 22 Escherichia coli (E. coli)
      auxotrophic deletion strains representative of the major nutrient biosynthetic
      pathways, we demonstrate that antimetabolite detection from actinomycete-derived
      extracts prepared using traditional extraction platforms is masked by nutrient
      supplementation. In particular, we find poor sensitivity for the detection of
      antimetabolites targeting vitamin biosynthesis. To circumvent this and as a proof
      of principle, we exploit the differential activity of actinomycete extracts
      against E. coli DeltayigM, a biotin transporter deletion strain versus wildtype
      E. coli. We achieve more than a 100-fold increase in antimetabolite sensitivity
      using this method and demonstrate a successful bioassay-guided purification of
      the known biotin antimetabolite, amiclenomycin. Our findings provide a unique
      solution to uncover the full potential of naturally derived antibiotics.

PMID- 29069548
TI  - Evidence of homologous and heterologous effects after unilateral leg training in
      youth.
AB  - The positive effects of unilateral training on contralateral muscles (cross
      education) has been demonstrated with adults for over a century. There is limited
      evidence for cross education of heterologous muscles. Cross education has not
      been demonstrated with children. It was the objective of this study to
      investigate cross-education training in children examining ipsilateral and
      contralateral homologous and heterologous muscles. Forty-eight male children
      (aged 10-13 years) were assessed for unilateral, ipsilateral and contralateral
      lower limb strength, power and endurance (1-repetition maximum (RM) leg press,
      knee extensors (KE) and flexors (KF) maximum voluntary isometric contractions
      (MVIC), countermovement jump, muscle endurance test (leg press repetitions with
      60% 1RM)), and upper body unilateral MVIC elbow flexors (EF) and handgrip
      strength. An 8-week training program involved 2 unilateral leg press resistance
      training groups (high load/low repetitions: 4-8 sets of 5RM, and low load/high
      repetitions: 1-2 sets of 20RM) and control (untrained) group. All muscles
      exhibited improvements of 6.1% to 89.1%. The trained limb exhibited greater
      adaptations than the untrained limb for leg press 1RM (40.3% vs. 25.2%; p =
      0.005), and 60% 1RM leg press (104.1% vs. 73.4%; p = 0.0001). The high load/low
      repetition training induced (p < 0.0001) greater improvements than low load/high
      repetition with KE, KF, EF MVIC and leg press 1RM. This is the first study to
      demonstrate cross-education effects with children and that the effects of
      unilateral training involve both contralateral homologous and heterologous
      muscles with the greatest strength-training responses from high-load/low
      repetition training.

PMID- 29069553
TI  - Button Magnets in the Nasal Cavity.

PMID- 29069554
TI  - Congenital Diaphragmatic Hernia.

PMID- 29069552
TI  - Xenopus embryos to study fetal alcohol syndrome, a model for environmental
      teratogenesis.
AB  - Vertebrate model systems are central to characterize the outcomes of ethanol
      exposure and the etiology of fetal alcohol spectrum disorder (FASD), taking
      advantage of their genetic and morphological closeness and similarity to humans.
      We discuss the contribution of amphibian embryos to FASD research, focusing on
      Xenopus embryos. The Xenopus experimental system is characterized by external
      development and accessibility throughout embryogenesis, large clutch sizes, gene
      and protein activity manipulation, transgenesis and genome editing, convenient
      chemical treatment, explants and conjugates, and many other experimental
      approaches. Taking advantage of these methods, many insights regarding FASD have
      been obtained. These studies characterized the malformations induced by ethanol
      including quantitative analysis of craniofacial malformations, induction of fetal
      growth restriction, delay in gut maturation, and defects in the differentiation
      of the neural crest. Mechanistic, biochemical, and molecular studies in Xenopus
      embryos identified early gastrula as the high alcohol sensitivity window,
      targeting the embryonic organizer and inducing a delay in gastrulation movements.
      Frog embryos have also served to demonstrate the involvement of reduced retinoic
      acid production and an increase in reactive oxygen species in FASD. Amphibian
      embryos have helped pave the way for our mechanistic, molecular, and biochemical
      understanding of the etiology and pathophysiology of FASD.

PMID- 29069557
TI  - The Price of Crossing the Border for Medications.

PMID- 29069547
TI  - Multifaceted Modularity: A Key for Stepwise Building of Hierarchical Complexity
      in Actinide Metal-Organic Frameworks.
AB  - Growing necessity for efficient nuclear waste management is a driving force for
      development of alternative architectures toward fundamental understanding of
      mechanisms involved in actinide (An) integration inside extended structures. In
      this manuscript, metal-organic frameworks (MOFs) were investigated as a model
      system for engineering radionuclide containing materials through utilization of
      unprecedented MOF modularity, which cannot be replicated in any other type of
      materials. Through the implementation of recent synthetic advances in the MOF
      field, hierarchical complexity of An-materials was built stepwise, which was only
      feasible due to preparation of the first examples of actinide-based frameworks
      with "unsaturated" metal nodes. The first successful attempts of solid-state
      metathesis and metal node extension in An-MOFs are reported, and the results of
      the former approach revealed drastic differences in chemical behavior of extended
      structures versus molecular species. Successful utilization of MOF modularity
      also allowed us to structurally characterize the first example of bimetallic An
      An nodes. To the best of our knowledge, through combination of solid-state
      metathesis, guest incorporation, and capping linker installation, we were able to
      achieve the highest Th wt % in mono- and biactinide frameworks with minimal
      structural density. Overall, the combination of a multistep synthetic approach
      with homogeneous actinide distribution and moderate solvothermal conditions could
      make MOFs an exceptionally powerful tool to address fundamental questions
      responsible for chemical behavior of An-based extended structures and, therefore,
      shed light on possible optimization of nuclear waste administration.

PMID- 29069559
TI  - The Success of Sinister Right-Handers in Baseball.

PMID- 29069561
TI  - Mandating Coverage for Fertility Preservation - A Step in the Right Direction.

PMID- 29069556
TI  - IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.

PMID- 29069560
TI  - Case 33-2017. 22-Month-Old Conjoined Twins.

PMID- 29069562
TI  - Dabigatran Reversal with Idarucizumab.

PMID- 29069565
TI  - Migraine.

PMID- 29069567
TI  - Officer of the Law.

PMID- 29069563
TI  - Abiraterone in Metastatic Prostate Cancer.

PMID- 29069558
TI  - Fertility Preservation in Women.

PMID- 29069572
TI  - Blood flow, volume and arterio-venous passages in induced mammary tumours of the
      rat.
AB  - OBJECTIVE: To study blood flow, vascular volume and arterio-venous passages in
      induced mammary tumours of the rat to characterize parameters possibly
      responsible for tumour hyponutrition. METHOD: Dimethylbenzanthracene-induced
      mammary tumours in Sprague-Dawley rats were studied. Regional blood flow was
      studied by use of the radioactive microsphere tracer technique using 141Cerium
      labelled 15MUm spheres coinjected into the left cardiac ventricle with 125Iodine
      labelled 25MUm spheres. Blood volume was studied by use of 125Iodine- or
      99mTechnetium-labelled human serum albumin, the latter allowing autoradiography
      of tumour sections for visualization of flow and volume. RESULTS: Twenty-seven
      rats with 170 tumours had a mean tumour blood flow of 48 and 67mL*min-1*100g-1
      using 15 and 25MUm sphere data, respectively, indicating a significant passage
      through vessels between 15 and 25MUm. The lungs showed a "nominal bronchial"
      blood flow of 260 and 135mL*min-1*100g-1 for the 15 and 25MUm spheres,
      respectively, indicating pulmonary trapping, particularly of small spheres
      passing the systemic circulation in vessels larger than 15MUm. There was a
      positive correlation between the total tumour blood flow within individual rats
      and trapped spheres of both dimensions in the lungs, indicating shunts also
      larger than 25MUm. Normal tissues disclosed only small differences in regional
      blood flow as measured by the two spheres. Blood volume was studied in 20 rats
      with 120 tumours, with a vascular volume of 3.6mL*100g-1 representing a blood
      turnover >15 times/min. Blood volume co-localized with perfusion as seen in
      autoradiographs. CONCLUSION: In induced rat mammary tumours, a high fraction of
      blood, 28%, passes arterio-venous vessels between 15 and 25MUm and there also
      exist passages >25MUm. These findings indicate that the functional capacity of
      the tumour vascular bed might be impaired, adding to the abnormal
      microenvironment of tumours.

PMID- 29069566
TI  - HIV Drug Resistance - An Emerging Threat to Epidemic Control.

PMID- 29069564
TI  - A CRISPR Way to Diagnose Infectious Diseases.

PMID- 29069569
TI  - The GlpF residue Trp219 is part of an amino-acid cluster crucial for
      aquaglyceroporin oligomerization and function.
AB  - The vestibule loop regions of aquaglyceroporins are involved in accumulation of
      glycerol inside the channel pore. Even though most loop regions do not show high
      sequence similarity among aquaglyceroporins, loop E is highly conserved in
      aquaglyceroporins, but not in members of the homologous aquaporins. Specifically,
      a tryptophan residue is extremely conserved within this loop. We have
      investigated the role of this residue (Trp219) that deeply protrudes into the
      protein and potentially interacts with adjacent loops, using the E. coli
      aqualgyeroporin GlpF as a model. Replacement of Trp219 affects the activity of
      GlpF and impairs the stability of the tetrameric protein. Furthermore, we have
      identified an amino acid cluster involving Trp219 that stabilizes the GlpF
      tetramer. Based on our results we propose that Trp219 is key for formation of a
      defined vestibule structure, which is crucial for glycerol accumulation as well
      as for the stability of the active GlpF tetramer.

PMID- 29069571
TI  - Low virulence potential and in vivo transformation ability in the honey bee venom
      treated Clinostomum complanatum.
AB  - The helminth parasites possess great capabilities to adapt themselves within
      their hosts and also develop strategies to render the commonly used anthelmintics
      ineffective leading to the development of resistance against these drugs. Besides
      using anthelmintics the natural products have also been tested for their anti
      parasitic effects. Therapeutic efficacy of honey bee venom (HBV) has been tested
      in various ailments including some protozoal infections but very little is known
      about its anthelmintic properties. To investigate the anthelmintic effect of HBV
      the excysted progenetic metacercariae of Clinostomum complanatum, a heamophagic,
      digenetic trematode with zoonotic potential, infecting a wide variety of hosts,
      were obtained from Trichogaster fasciatus, a forage fish, which serves as the
      intermediate host. The metacercarial worms were in vitro incubated in RPMI-1640
      medium containing HBV along with the controls which were devoid of HBV for the
      analysis of worm motility, enzyme activity, polypeptide profile and surface
      topographical changes. The motility of the worms was significantly reduced in a
      time dependent manner with an increase in the concentration of HBV. Following
      incubation of worms the release of cysteine proteases was inhibited in the
      presence of HBV as revealed by gelatine substrate gel zymography. As well as the
      polypeptide profile was also significantly influenced, particularly
      intensity/expression of Mr 19.4 kDa, 24 kDa and 34 kDa was significantly reduced
      upon HBV treatment. The HBV treatment also inhibited antioxidant enzyme,
      superoxide dismutase (SOD) and Glutathione-S-transferase (GST) significantly (p <
      0.05) in the worms. The scanning electron microscopy of the HBV treated worms
      revealed tegumental disruptions and erosion of papillae as well as spines showing
      vacuolation in the tegument. The HBV treated worms also showed a marked decline
      in the transformation rate when introduced into an experimental host which
      further reflect the anthelmintic potential of HBV.

PMID- 29069577
TI  - Mutant p53 as a therapeutic target for the treatment of triple-negative breast
      cancer: Preclinical investigation with the anti-p53 drug, PK11007.
AB  - The identification of a targeted therapy for patients with triple-negative breast
      cancer (TNBC) is one of the most urgent needs in breast cancer therapeutics. The
      p53 gene is mutated in approximately 80% of patients with TNBC, and is a
      potential therapeutic target for patients with this form of breast cancer. The 2
      sulfonylpyrimidine compound, PK11007, preferentially decreases viability in p53
      compromised cancer cell lines. We investigated PK11007 as a potential new
      treatment for TNBC. IC50 values for inhibition of proliferation in a panel of 17
      breast cell lines by PK11007 ranged from 2.3 to 42.2 MUM. There were
      significantly lower IC50 values for TNBC than for non-TNBC cell lines (p = 0.03)
      and for p53-mutated cell lines compared with p53 WT cells (p = 0.003). Response
      to PK11007 however, was independent of the estrogen receptor (ER) or HER2 status
      of the cell lines. In addition to inhibiting cell proliferation, PK11007 induced
      apoptosis in p53 mutant cell lines. Using RNAseq and gene ontology analysis, we
      found that PK11007 altered the expression of genes enriched in pathways involved
      in regulated cell death, regulation of apoptosis, signal transduction, protein
      refolding and locomotion. The observations that PK11007 inhibited cell
      proliferation, induced apoptosis and altered genes involved in cell death are all
      consistent with the ability of PK11007 to reactivate mutant p53. Based on our
      data, we conclude that targeting mutant p53 with PK11007 is a potential approach
      for treating p53-mutated breast cancer, including the subgroup with TN disease.

PMID- 29069574
TI  - Extracellular trap-like fiber release may not be a prominent defence response in
      snails: evidence from three species of freshwater gastropod molluscs.
AB  - The discovery that mammalian neutrophils generate extracellular chromatin fibers
      that entrap/kill bacteria supported a new paradigm for innate immunity in
      animals. Similar findings in other models across diverse taxa have led to the
      hypothesis that the phenomenon is ancient and evolutionary conserved. Here, using
      a variety of synthetic (e.g. peptidoglycan) and biological (e.g. trematode
      larvae) components to investigate extracellular trap-like (ET-like) fiber
      production in vitro by haemocytes of Lymnaea stagnalis, Radix lagotis and
      Planorbarius corneus snails, ET-like fibers were rarely observed. We suggest,
      therefore, that ET-like fibers play a marginal role in defence of these snail
      species and thus the fiber production may not be a critical process underpinning
      immunity in all invertebrate species.

PMID- 29069568
TI  - Surgery for Drug-Resistant Epilepsy in Children.
AB  - BACKGROUND: Neurosurgical treatment may improve seizures in children and
      adolescents with drug-resistant epilepsy, but additional data are needed from
      randomized trials. METHODS: In this single-center trial, we randomly assigned 116
      patients who were 18 years of age or younger with drug-resistant epilepsy to
      undergo brain surgery appropriate to the underlying cause of epilepsy along with
      appropriate medical therapy (surgery group, 57 patients) or to receive medical
      therapy alone (medical-therapy group, 59 patients). The patients in the medical
      therapy group were assigned to a waiting list for surgery. The primary outcome
      was freedom from seizures at 12 months. Secondary outcomes were the score on the
      Hague Seizure Severity scale, the Binet-Kamat intelligence quotient, the social
      quotient on the Vineland Social Maturity Scale, and scores on the Child Behavior
      Checklist and the Pediatric Quality of Life Inventory. RESULTS: At 12 months,
      freedom from seizures occurred in 44 patients (77%) in the surgery group and in 4
      (7%) in the medical-therapy group (P<0.001). Between-group differences in the
      change from baseline to 12 months significantly favored surgery with respect to
      the score on the Hague Seizure Severity scale (difference, 19.4; 95% confidence
      interval [CI], 15.8 to 23.1; P<0.001), on the Child Behavior Checklist
      (difference, 13.1; 95% CI, 10.7 to 15.6; P<0.001), on the Pediatric Quality of
      Life Inventory (difference, 21.9; 95% CI, 16.4 to 27.6; P<0.001), and on the
      Vineland Social Maturity Scale (difference, 4.7; 95% CI, 0.4 to 9.1; P=0.03), but
      not on the Binet-Kamat intelligence quotient (difference, 2.5; 95% CI, -0.1 to
      5.1; P=0.06). Serious adverse events occurred in 19 patients (33%) in the surgery
      group, including hemiparesis in 15 (26%). CONCLUSIONS: In this single-center
      trial, children and adolescents with drug-resistant epilepsy who had undergone
      epilepsy surgery had a significantly higher rate of freedom from seizures and
      better scores with respect to behavior and quality of life than did those who
      continued medical therapy alone at 12 months. Surgery resulted in anticipated
      neurologic deficits related to the region of brain resection. (Funded by the
      Indian Council of Medical Research and others; Clinical Trial Registry-India
      number, CTRI/2010/091/000525 .).

PMID- 29069570
TI  - The effect of drug binding on specific sites in transmembrane helices 4 and 6 of
      the ABC exporter MsbA studied by DNP-enhanced solid-state NMR.
AB  - MsbA, a homodimeric ABC exporter, translocates its native substrate lipid A as
      well as a range of smaller, amphiphilic substrates across the membrane. Magic
      angle sample spinning (MAS) NMR, in combination with dynamic nuclear polarization
      (DNP) for signal enhancement, has been used to probe two specific sites in
      transmembrane helices 4 and 6 of full length MsbA embedded in lipid bilayers.
      Significant chemical shift changes in both sites were observed in the vanadate
      trapped state compared to apo state MsbA. The reduced spectral line width
      indicates a more confined conformational space upon trapping. In the presence of
      substrates Hoechst 33342 and daunorubicin, further chemical shift changes and
      line shape alterations mainly in TM6 in the vanadate trapped state were detected.
      These data illustrate the conformational response of MsbA towards the presence of
      drugs during the catalytic cycle. This article is part of a Special Issue
      entitled: Beyond the Structure-Function Horizon of Membrane Proteins edited by
      Ute Hellmich, Rupak Doshi and Benjamin McIlwain.

PMID- 29069575
TI  - Up-regulation of caveolin-1 by DJ-1 attenuates rat pulmonary arterial
      hypertension by inhibiting TGFbeta/Smad signaling pathway.
AB  - Pulmonary arterial hypertension (PAH), characterized by excessive proliferation
      and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs), is
      closely associated with the imbalance in vasoactive mediators and massive
      remodeling of pulmonary vasculature. DJ-1/park7, a multifunctional protein, plays
      a critical defense role in several cytobiological activity, such as
      transcriptional regulation, anti-oxidative stress and tumor formation. In this
      study, we investigated the effects of DJ-1 on hypoxia-induced PAH model rats and
      PASMCs, as well as its possible molecular mechanism. First, the low expressions
      of DJ-1 and caveolin-1 (Cav-1) were synchronously detected in lung tissue of PAH
      model rats and hypoxia-induced PASMCs by Western blot. Then, the DJ-1 wild type
      (WT) or Knock out (KO) rats were exposed to chronic hypoxia to mimic a hypoxic
      PAH condition. The protein level of Cav-1 was markedly decreased in the tissue of
      DJ-1 KO rats, and additionally lower in tissue of the hypoxia group than that in
      the normoxia group for DJ-1 WT and KO rats. In vivo, hemodynamic data showed that
      the pulmonary arterial pressure (mPAP), right ventricle systolic pressure (RVSP)
      and pulmonary arterial systolic pressure (PASP), as well as the weight of the
      right ventricle/left ventricle plus septum (RV/LV+S) ratio of PAH model rats were
      higher in the DJ-1 KO group than those in the DJ-1 WT group. Moreover, knockout
      of DJ-1 also results in the phenotype switch from contractile to synthetic PASMC,
      which is reflected by reduced calponin and SM22alpha expressions. In vitro, DJ-1
      overexpression reversed hypoxia-induced elevation of PASMC cell proliferation,
      migration and Ca2+ concentration, which were not obviously observed in Cav-1
      shRNA (sh-Cav-1) and DJ-1 co-transfected cells. Then the increased levels of
      calponin and SM22alpha were detected in the DJ-1 group; similarly those levels
      were not changed in the DJ-1+sh-Cav-1 group. Finally, the expression of TGFbeta1,
      p-Smad2 and p-Smad3 were obviously decreased in the ad-DJ-1 group, however those
      were all elevated in the DJ-1 and sh-Cav-1 co-transfected groups. In conclusion,
      these results indicate that DJ-1 may alleviate hypoxia-induced PASMCs injury by
      Cav-1 through inhibiting the TGFbeta/Smad signaling pathway.

PMID- 29069573
TI  - Sulforaphane restores acetyl-histone H3 binding to Bcl-2 promoter and prevents
      apoptosis in ethanol-exposed neural crest cells and mouse embryos.
AB  - Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables.
      SFN's cytoprotective properties have been demonstrated in several models
      associated with a variety of disorders. Our recent studies have shown that SFN
      protects against ethanol-induced oxidative stress and apoptosis in neural crest
      cells (NCCs), an ethanol-sensitive cell population implicated in Fetal Alcohol
      Spectrum Disorders (FASD). This study is designed to test the hypothesis that SFN
      can prevent ethanol-induced apoptosis in NCCs by inhibiting HDAC and increasing
      histone acetylation at the Bcl-2 promoter. We found that exposure to 50mM ethanol
      resulted in a significant increase in HDAC activities in NCCs. Treatment with SFN
      decreased the activities of HDAC in ethanol-exposed NCCs. We also found that SFN
      treatment significantly increased the expression of acetyl-histone H3 in NCCs
      treated with ethanol. ChIP-qPCR assay revealed that ethanol exposure
      significantly decreased acetyl-histone H3 binding to the Bcl-2 promoter while
      supplementing with SFN reversed the ethanol-induced reduction in acetyl-histone
      H3 binding to the Bcl-2 promoter. In addition, SFN treatment restored the
      expression of Bcl-2 in ethanol-exposed NCCs and diminished ethanol-induced
      apoptosis in NCCs. Treatment with SFN also significantly diminished apoptosis in
      mouse embryos exposed to ethanol in vivo. These results demonstrate that SFN can
      epigenetically restore the expression of Bcl-2 and attenuate ethanol-induced
      apoptosis by increasing histone acetylation at the Bcl-2 promoter and suggest
      that SFN may prevent FASD through epigenetic regulation of the expression of anti
      apoptotic genes.

PMID- 29069578
TI  - LOX-1 mediated phenotypic switching of pulmonary arterial smooth muscle cells
      contributes to hypoxic pulmonary hypertension.
AB  - In pulmonary hypertension (PH), pulmonary arterial smooth muscle cells (PASMCs)
      are dedifferentiated, undergoing a contractile-to-synthetic phenotypic switching.
      Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) plays diverse
      roles in the cardiovascular system, but its contribution to PH remains to be
      fully defined. The present study was undertaken to explore the role of LOX-1 in
      PASMCs dedifferentiation in hypoxia-induced pulmonary vascular remodeling and PH.
      In a rat model of hypoxic PH, pulmonary vascular remodeling was accompanied by
      increased expression of LOX-1 in pulmonary arteries. In primary rat PASMCs,
      hypoxia-induced PASMCs dedifferentiation occurred concomitantly with LOX-1
      upregulation. Inhibition of LOX-1 by either siRNA knockdown or neutralizing
      antibody significantly ameliorated PASMCs dedifferentiation. Mechanistically, LOX
      1 promotes PASMCs dedifferentiation under hypoxic conditions via ERK1/2-Elk
      1/MRTF-A/SRF signaling pathway. In conclusion, our data uncovers an important
      role of LOX-1 in the maintenance of PASMCs phenotype. Therapeutic targeting of
      LOX-1/ERK1/2-Elk-1/MRTF-A/SRF signaling axis would be exploited to treat hypoxic
      PH.

PMID- 29069576
TI  - Novel combination of histone methylation modulators with therapeutic synergy
      against acute myeloid leukemia in vitro and in vivo.
AB  - Acute myeloid leukemia (AML) is a hematological malignancy with rapid disease
      progression and often becomes lethal without treatment. Development of effective
      new therapies is essential to improve the clinical outcome of AML patients.
      Enhancer of zeste homolog 2 (EZH2) and lysine specific demethylase 1 (LSD1) play
      important roles in epigenetic regulation and their altered expressions have been
      observed in cancer. Although EZH2 and LSD1 have opposite histone methylation
      functions, we found that both enzymes were paradoxically up-regulated in AML
      cells. Importantly, a combined inhibition of EZH2 and LSD1 resulted in a
      synergistic activity against AML in vitro and in vivo. Such synergy was
      mechanistically correlated with up-regulation of H3K4me1/2 and H3K9Ac and down
      regulation of H3K27me3, leading to a decrease of anti-apoptotic protein Bcl-2.
      These epigenetic alterations also compromised the mitochondrial respiration
      capacity and glycolytic activity and resulted in ATP depletion, a key event
      contributing to the potent cytotoxic effect of the drug combination. Taken
      together, our work identified a novel therapeutic approach against AML by
      combining two small molecules that inhibit different histone methylation
      modulating proteins with apparently opposite enzyme activities. Such a new drug
      combination strategy likely has significant clinical implications since
      epigenetic modulators are currently in clinical trials.

PMID- 29069579
TI  - Blockade of endothelin receptors reduces tumor-induced ongoing pain and evoked
      hypersensitivity in a rat model of facial carcinoma induced pain.
AB  - Pain reported by patients with head and neck cancer is characterized as
      persistent pain with mechanical allodynia. Pain management is inadequate for many
      patients, highlighting the need for improved therapies. We examined the
      hypothesis that the mixed endothelin ETA and ETB receptor antagonist, bosentan,
      reduces tumor-induced ongoing pain and evoked hypersensitivity in a rat model of
      facial cancer pain. Facial cancer was induced by inoculating a suspension of
      Walker-256 cells into the rat's right vibrissal pad. Tumor-bearing rats developed
      heat and tactile hypersensitivity along with increased spontaneous grooming
      behavior. Systemic morphine (2.5mg/kg, s.c.) blocked tumor-induced thermal and
      tactile hypersensitivity, with a lower dose (0.625mg/kg, s.c.) effective only
      against thermal hypersensitivity. Systemic bosentan blocked tumor-induced thermal
      hypersensitivity only at a high (300mg/kg, p.o.) dose, but failed to modify
      tactile hypersensitivity. Co-administration of the low doses of bosentan and
      morphine resulted in improved reduction of the tumor-induced heat and tactile
      hypersensitivity compared to either dose alone. Bosentan (100mg/kg, p.o.) reduced
      spontaneous grooming and induced conditioned place preference (CPP) selectively
      in tumor-bearing rats, suggesting that bosentan reduces tumor-induced ongoing
      pain at a lower dose than required to block tumor-induced hypersensitivity. This
      study provides evidence that endothelins may mediate tumor-induced ongoing pain
      and thermal hypersensitivity. In addition, bosentan enhanced morphine's effects
      on blocking tumor-induced heat and tactile hypersensitivity indicating that
      endothelin antagonists may be beneficial therapeutic targets that can be used to
      manage cancer-induced facial pain with opioid-sparing effects.

PMID- 29069581
TI  - Aligning nanotoxicology with the 3Rs: What is needed to realise the short, medium
      and long-term opportunities?
AB  - Nanomaterials convey numerous advantages, and the past decade has seen a
      considerable rise in their development and production for an expanse of
      applications. While the potential advantages of nanomaterials are clear, concerns
      over the impact of human and environmental exposure exist. Concerted, science-led
      efforts are required to understand the effects of nanomaterial exposure and
      ensure that protection goals are met. There is much on-going discussion regarding
      how best to assess nanomaterial risk, particularly considering the large number
      of tests that may be required. A plethora of forms may need to be tested for each
      nanomaterial, and risk assessed throughout the life cycle, meaning numerous acute
      and chronic toxicity studies could be required, which is neither practical nor
      utilises the current evidence-base. Hence, there are scientific, business,
      ethical and legislative drivers to re-consider the use of animal toxicity tests.
      An expert Working Group of regulators, academics and industry scientists were
      gathered by the UK's NC3Rs to discuss: i) opportunities being offered in the
      short, medium and long-terms to advance nanosafety, ii) how to align these
      advances with the application of the 3Rs in nanomaterial safety testing, and iii)
      shifting the focus of risk assessment from current hazard-based approaches
      towards exposure-driven approaches.

PMID- 29069582
TI  - Assessment of the potential human health risks from exposure to complex
      substances in accordance with REACH requirements. "White spirit" as a case study.
AB  - The European chemical control regulation (REACH) requires that data on
      physical/chemical, toxicological and environmental hazards be compiled.
      Additionally, REACH requires formal assessments to ensure that substances can be
      safely used for their intended purposes. For health hazard assessments, reference
      values (Derived No Effect levels, DNELs) are calculated from toxicology data and
      compared to estimated exposure levels. If the ratio of the predicted exposure
      level to the DNEL, i.e. the Risk Characterization Ratio (RCR), is less than 1,
      the risk is considered controlled; otherwise, additional Risk Management Measures
      (RMM) must be applied. These requirements pose particular challenges for complex
      substances. Herein, "white spirit", a complex hydrocarbon solvent, is used as an
      example to illustrate how these procedures were applied. Hydrocarbon solvents
      were divided into categories of similar substances. Representative substances
      were identified for DNEL determinations. Adjustment factors were applied to the
      no effect levels to calculate the DNELs. Exposure assessments utilized a
      standardized set of generic exposure scenarios (GES) which incorporated exposure
      predictions for solvent handling activities. Computer-based tools were developed
      to automate RCR calculations and identify appropriate RMMs, allowing consistent
      communications to users via safety data sheets.

PMID- 29069583
TI  - shRNA interference of NLRP3 inflammasome alleviate ischemia reperfusion-induced
      myocardial damage through autophagy activation.
AB  - Myocardial ischemia-reperfusion (I/R) injury always occur during the recovery of
      myocardial blood supply with high morbidity and mortality. Although, various
      therapeutic schedules were applied in clinic, there are real problems that have
      to be resolved on curative effect. Nod-like receptor protein 3 (NLRP3)
      inflammasome has moderation effects on cellular damage and inflammatory reaction
      after I/R injury. Our research aims to investigate a more effective approach to
      restrain the activation of NLRP3 inflammasome in treating myocardial I/R injury.
      Results indicated that cell viability, Bax/Bcl-2 expression were affected hardly
      by sh-NLRP3 transfection in normal cells. However, the decreased cell viability
      and increased Bax/Bcl-2 expression level caused by I/R were remarkably suppressed
      through sh-NLRP3 transfection. Besides that, the reduced levels of pro-autophagy
      proteins (Beclin1, Agt7, LC3II/LC3I) while enhanced level of anti-autophagy
      protein (p62) and apoptosis-related proteins (Bax/Bcl-2) were significantly
      repressed via sh-NLRP3 transfection. Nevertheless, the autophagy inhibitor 3 MA
      could reverse the results. Moreover, in vivo experiment suggested that NLRP3 was
      up-regulated in wild type (WT) rats with I/R injury. The expansion of infarct
      size induced by ischemia was tremendously constricted in NLRP3 knockout (KO)
      rats. NLRP3 silence had nearly no impact on myocardial enzymes (AST, LDH and CK)
      expressions, inflammatory factors (TNF-alpha and IL-1beta) expressions and cell
      apoptosis in rats without I/R injury. Nonetheless, the elevated levels of
      myocardial enzymes, inflammatory factors and cell apoptosis caused by I/R injury
      were vastly inhibited in NLRP3 KO rats. Furthermore, NLRP3 KO itself would lead
      to higher level of pro-autophagy proteins (Beclin1, Agt7, LC3II/LC3I) while lower
      level of anti-autophagy protein (p62) in vivo. The decreased expressions of pro
      autophagy proteins while increased expressions of anti-autophagy protein induced
      by I/R injury were remarkably suppressed by NLRP3 KO. Taken together, our study
      indicated that shRNA interference of NLRP3 inflammasome attenuated myocardial I/R
      injury via autophagy activation. These findings demonstrated that NLRP3 KO may a
      promising therapy in myocardial I/R injury.

PMID- 29069586
TI  - Fumarate Hydratase Loss Causes Combined Respiratory Chain Defects.
AB  - Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid (TCA) cycle
      mutated in hereditary and sporadic cancers. Despite recent advances in
      understanding its role in tumorigenesis, the effects of FH loss on mitochondrial
      metabolism are still unclear. Here, we used mouse and human cell lines to assess
      mitochondrial function of FH-deficient cells. We found that human and mouse FH
      deficient cells exhibit decreased respiration, accompanied by a varying degree of
      dysfunction of respiratory chain (RC) complex I and II. Moreover, we show that
      fumarate induces succination of key components of the iron-sulfur cluster
      biogenesis family of proteins, leading to defects in the biogenesis of iron
      sulfur clusters that affect complex I function. We also demonstrate that
      suppression of complex II activity is caused by product inhibition due to
      fumarate accumulation. Overall, our work provides evidence that the loss of a
      single TCA cycle enzyme is sufficient to cause combined RC activity dysfunction.

PMID- 29069580
TI  - Nicotinamide prevents sweet beverage-induced hepatic steatosis in rats by
      regulating the G6PD, NADPH/NADP+ and GSH/GSSG ratios and reducing oxidative and
      inflammatory stress.
AB  - The disruption of redox state homeostasis, the overexpression of lipogenic
      transcription factors and enzymes, and the increase in lipogenic precursors
      induced by sweetened beverages are determinants of the development of
      nonalcoholic fatty liver disease. This study evaluated the action of nicotinamide
      (NAM) on the expression of glucose-6-phosphate dehydrogenase (G6PD) and redox,
      oxidative, and inflammatory states in a model of nonalcoholic hepatic steatosis
      induced by high and chronic consumption of carbohydrates. Male rats were provided
      drinking water with 30% glucose or fructose ad libitum for 12 weeks.
      Additionally, 30 days after the beginning of carbohydrate administration, some
      rats were simultaneously provided water with 0.06% or 0.12% NAM for 5h daily over
      the next 8 weeks. Biochemical profiles and expression levels of G6PD, tumor
      necrosis factor alpha (TNFalpha), and NADPH oxidase 4 (NOX4) were evaluated
      together with glutathione/glutathione disulfide (GSH/GSSG) and reduced
      nicotinamide adenine dinucleotide (phosphate)/nicotinamide adenine dinucleotide
      (phosphate) [NAD(P)H/NAD(P)] ratios and thiobarbituric acid reactive substances
      (TBARS). The results showed that hepatic steatosis induced by the chronic
      consumption of glucose or fructose was associated with body weight gain and
      increased levels of serum glucose, insulin, triacylglycerols, free fatty acids,
      transaminases, and TBARS. In the liver, the expression and activity of G6PD
      increased along with the GSSG, TBARS, and TG concentrations. These alterations
      were reduced by NAM treatment through the attenuation of increases in G6PD
      expression and activity and in the NADPH/NADP+ ratio, thereby slowing liver
      steatosis. NAM prevents redox, oxidative, and inflammatory alterations induced by
      high carbohydrate consumption.

PMID- 29069585
TI  - Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes
      Systemic Insulin Resistance and Impairs Glucose Transport.
AB  - Lower adipose-ChREBP and de novo lipogenesis (DNL) are associated with insulin
      resistance in humans. Here, we generated adipose-specific ChREBP knockout
      (AdChREBP KO) mice with negligible sucrose-induced DNL in adipose tissue (AT).
      Chow-fed AdChREBP KO mice are insulin resistant with impaired insulin action in
      the liver, muscle, and AT and increased AT inflammation. HFD-fed AdChREBP KO mice
      are also more insulin resistant than controls. Surprisingly, adipocytes lacking
      ChREBP display a cell-autonomous reduction in insulin-stimulated glucose
      transport that is mediated by impaired Glut4 translocation and exocytosis, not
      lower Glut4 levels. AdChREBP KO mice have lower levels of palmitic acid esters of
      hydroxy stearic acids (PAHSAs) in serum, and AT. 9-PAHSA supplementation
      completely rescues their insulin resistance and AT inflammation. 9-PAHSA also
      normalizes impaired glucose transport and Glut4 exocytosis in ChREBP KO
      adipocytes. Thus, loss of adipose-ChREBP is sufficient to cause insulin
      resistance, potentially by regulating AT glucose transport and flux through
      specific lipogenic pathways.

PMID- 29069584
TI  - Dendritic Cell Amiloride-Sensitive Channels Mediate Sodium-Induced Inflammation
      and Hypertension.
AB  - Sodium accumulates in the interstitium and promotes inflammation through poorly
      defined mechanisms. We describe a pathway by which sodium enters dendritic cells
      (DCs) through amiloride-sensitive channels including the alpha and gamma subunits
      of the epithelial sodium channel and the sodium hydrogen exchanger 1. This leads
      to calcium influx via the sodium calcium exchanger, activation of protein kinase
      C (PKC), phosphorylation of p47phox, and association of p47phox with gp91phox.
      The assembled NADPH oxidase produces superoxide with subsequent formation of
      immunogenic isolevuglandin (IsoLG)-protein adducts. DCs activated by excess
      sodium produce increased interleukin-1beta (IL-1beta) and promote T cell
      production of cytokines IL-17A and interferon gamma (IFN-gamma). When adoptively
      transferred into naive mice, these DCs prime hypertension in response to a sub
      pressor dose of angiotensin II. These findings provide a mechanistic link between
      salt, inflammation, and hypertension involving increased oxidative stress and
      IsoLG production in DCs.

PMID- 29069555
TI  - Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.
AB  - BACKGROUND: Detailed neuropathological information on the structural brain
      lesions underlying seizures is valuable for understanding drug-resistant focal
      epilepsy. METHODS: We report the diagnoses made on the basis of resected brain
      specimens from 9523 patients who underwent epilepsy surgery for drug-resistant
      seizures in 36 centers from 12 European countries over 25 years.
      Histopathological diagnoses were determined through examination of the specimens
      in local hospitals (41%) or at the German Neuropathology Reference Center for
      Epilepsy Surgery (59%). RESULTS: The onset of seizures occurred before 18 years
      of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery
      as adults. The mean duration of epilepsy before surgical resection was 20.1 years
      among adults and 5.3 years among children. The temporal lobe was involved in
      71.9% of operations. There were 36 histopathological diagnoses in seven major
      disease categories. The most common categories were hippocampal sclerosis, found
      in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly
      ganglioglioma) in 23.6%, and malformations of cortical development in 19.8%
      (focal cortical dysplasia was the most common type, 52.7% of cases of which were
      in children). No histopathological diagnosis could be established for 7.7% of the
      patients. CONCLUSIONS: In patients with drug-resistant focal epilepsy requiring
      surgery, hippocampal sclerosis was the most common histopathological diagnosis
      among adults, and focal cortical dysplasia was the most common diagnosis among
      children. Tumors were the second most common lesion in both groups. (Funded by
      the European Union and others.).

PMID- 29069587
TI  - Biophysical Variation within the M1 Type of Ganglion Cell Photoreceptor.
AB  - Intrinsically photosensitive retinal ganglion cells of the M1 type encode
      environmental irradiance for functions that include circadian and pupillary
      regulation. Their distinct role, morphology, and molecular markers indicate that
      they are stereotyped circuit elements, but their physiological uniformity has not
      been investigated in a systematic fashion. We have profiled the biophysical
      parameters of mouse M1s and found that extreme variation is their hallmark. Most
      parameters span 1-3 log units, and the full range is evident in M1s that
      innervate brain regions serving divergent functions. Biophysical profiles differ
      among cells possessing similar morphology and between neighboring M1s recorded
      simultaneously. Variation in each parameter is largely independent of that in
      others, allowing for flexible individualization. Accordingly, a common stimulus
      drives heterogeneous spike outputs across cells. By contrast, a population of
      directionally selective retinal ganglion cells appeared physiologically uniform
      under similar conditions. Thus, M1s lack biophysical constancy and send diverse
      signals downstream.

PMID- 29069588
TI  - Signatures of Nucleotide Analog Incorporation by an RNA-Dependent RNA Polymerase
      Revealed Using High-Throughput Magnetic Tweezers.
AB  - RNA viruses pose a threat to public health that is exacerbated by the dearth of
      antiviral therapeutics. The RNA-dependent RNA polymerase (RdRp) holds promise as
      a broad-spectrum, therapeutic target because of the conserved nature of the
      nucleotide-substrate-binding and catalytic sites. Conventional, quantitative,
      kinetic analysis of antiviral ribonucleotides monitors one or a few incorporation
      events. Here, we use a high-throughput magnetic tweezers platform to monitor the
      elongation dynamics of a prototypical RdRp over thousands of nucleotide-addition
      cycles in the absence and presence of a suite of nucleotide analog inhibitors. We
      observe multiple RdRp-RNA elongation complexes; only a subset of which are
      competent for analog utilization. Incorporation of a pyrazine-carboxamide
      nucleotide analog, T-1106, leads to RdRp backtracking. This analysis reveals a
      mechanism of action for this antiviral ribonucleotide that is corroborated by
      cellular studies. We propose that induced backtracking represents a distinct
      mechanistic class of antiviral ribonucleotides.

PMID- 29069589
TI  - Understanding Tissue-Specific Gene Regulation.
AB  - Although all human tissues carry out common processes, tissues are distinguished
      by gene expression patterns, implying that distinct regulatory programs control
      tissue specificity. In this study, we investigate gene expression and regulation
      across 38 tissues profiled in the Genotype-Tissue Expression project. We find
      that network edges (transcription factor to target gene connections) have higher
      tissue specificity than network nodes (genes) and that regulating nodes
      (transcription factors) are less likely to be expressed in a tissue-specific
      manner as compared to their targets (genes). Gene set enrichment analysis of
      network targeting also indicates that the regulation of tissue-specific function
      is largely independent of transcription factor expression. In addition, tissue
      specific genes are not highly targeted in their corresponding tissue network.
      However, they do assume bottleneck positions due to variability in transcription
      factor targeting and the influence of non-canonical regulatory interactions.
      These results suggest that tissue specificity is driven by context-dependent
      regulatory paths, providing transcriptional control of tissue-specific processes.

PMID- 29069591
TI  - Tracking the Same Neurons across Multiple Days in Ca2+ Imaging Data.
AB  - Ca2+ imaging techniques permit time-lapse recordings of neuronal activity from
      large populations over weeks. However, without identifying the same neurons
      across imaging sessions (cell registration), longitudinal analysis of the neural
      code is restricted to population-level statistics. Accurate cell registration
      becomes challenging with increased numbers of cells, sessions, and inter-session
      intervals. Current cell registration practices, whether manual or automatic, do
      not quantitatively evaluate registration accuracy, possibly leading to data
      misinterpretation. We developed a probabilistic method that automatically
      registers cells across multiple sessions and estimates the registration
      confidence for each registered cell. Using large-scale Ca2+ imaging data recorded
      over weeks from the hippocampus and cortex of freely behaving mice, we show that
      our method performs more accurate registration than previously used routines,
      yielding estimated error rates <5%, and that the registration is scalable for
      many sessions. Thus, our method allows reliable longitudinal analysis of the same
      neurons over long time periods.

PMID- 29069590
TI  - The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of
      GPCRs.
AB  - G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell
      surface signaling proteins. However, mechanisms underlying their surface
      targeting and sorting are poorly understood. Here, we screen the Rab family of
      small GTPases in the surface transport of multiple GPCRs. We find that
      manipulation of Rab43 function significantly alters the surface presentation and
      signaling of all GPCRs studied without affecting non-GPCR membrane proteins.
      Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic
      reticulum (ER) to the Golgi. More interestingly, Rab43 directly interacts with
      GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in
      the receptors effectively converts non-GPCR membrane protein transport into a
      Rab43-dependent pathway. These data reveal a crucial role for Rab43 in
      anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of
      GPCR members by virtue of its ability to interact directly.

PMID- 29069592
TI  - Mass Cytometric Analysis Reveals Viable Activated Caspase-3+ Luminal Progenitors
      in the Normal Adult Human Mammary Gland.
AB  - The normal adult human female mammary gland is a bilayered structure consisting
      of an outer basal layer and two readily distinguished subsets of cells within the
      inner luminal layer. We now present a validated methodology for undertaking large
      scale multi-parameter mass cytometric analyses of these cell types at single-cell
      resolution. In addition, we show how combining this approach with in vitro
      clonogenic assays of the proliferative and signaling responses of normal human
      mammary cells to epidermal growth factor (EGF) allows additional subsets with
      different EGF responses to be discerned. This included the identification of a
      subset of cells within the phenotypically defined luminal progenitor fraction
      that displays an elevated content of active caspase-3, including some that
      generate clones in vitro in response to EGF, with immunohistochemical evidence of
      their presence in situ in fixed preparations of normal human breast tissue.

PMID- 29069593
TI  - Phospholipid Homeostasis Regulates Dendrite Morphogenesis in Drosophila Sensory
      Neurons.
AB  - Disruptions in lipid homeostasis have been observed in many neurodevelopmental
      disorders that are associated with dendrite morphogenesis defects. However, the
      molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are
      unclear. We find that easily shocked (eas), which encodes a kinase with a
      critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two
      other enzymes in this synthesis pathway are required cell autonomously in sensory
      neurons for dendrite growth and stability. Furthermore, we show that the level of
      Sterol Regulatory Element-Binding Protein (SREBP) activity is important for
      dendrite development. SREBP activity increases in eas mutants, and decreasing the
      level of SREBP and its transcriptional targets in eas mutants largely suppresses
      the dendrite growth defects. Furthermore, reducing Ca2+ influx in neurons of eas
      mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role
      for EAS kinase and reveals the in vivo function of phospholipid homeostasis in
      dendrite morphogenesis.

PMID- 29069594
TI  - Columnar-Intrinsic Cues Shape Premotor Input Specificity in Locomotor Circuits.
AB  - Control of movement relies on the ability of circuits within the spinal cord to
      establish connections with specific subtypes of motor neuron (MN). Although the
      pattern of output from locomotor networks can be influenced by MN position and
      identity, whether MNs exert an instructive role in shaping synaptic specificity
      within the spinal cord is unclear. We show that Hox transcription-factor
      dependent programs in MNs are essential in establishing the central pattern of
      connectivity within the ventral spinal cord. Transformation of axially projecting
      MNs to a limb-level lateral motor column (LMC) fate, through mutation of the
      Hoxc9 gene, causes the central afferents of limb proprioceptive sensory neurons
      to target MNs connected to functionally inappropriate muscles. MN columnar
      identity also determines the pattern and distribution of inputs from multiple
      classes of premotor interneurons, indicating that MNs broadly influence circuit
      connectivity. These findings indicate that MN-intrinsic programs contribute to
      the initial architecture of locomotor circuits.

PMID- 29069595
TI  - Cortical Interneurons Differentially Shape Frequency Tuning following Adaptation.
AB  - Neuronal stimulus selectivity is shaped by feedforward and recurrent excitatory
      inhibitory interactions. In the auditory cortex (AC), parvalbumin- (PV) and
      somatostatin-positive (SOM) inhibitory interneurons differentially modulate
      frequency-dependent responses of excitatory neurons. Responsiveness of neurons in
      the AC to sound is also dependent on stimulus history. We found that the
      inhibitory effects of SOMs and PVs diverged as a function of adaptation to
      temporal repetition of tones. Prior to adaptation, suppressing either SOM or PV
      inhibition drove both increases and decreases in excitatory spiking activity.
      After adaptation, suppressing SOM activity caused predominantly disinhibitory
      effects, whereas suppressing PV activity still evoked bi-directional changes.
      SOM, but not PV-driven inhibition, dynamically modulated frequency tuning with
      adaptation. Unlike PV-driven inhibition, SOM-driven inhibition elicited gain-like
      increases in frequency tuning reflective of adaptation. Our findings suggest that
      distinct cortical interneurons differentially shape tuning to sensory stimuli
      across the neuronal receptive field, altering frequency selectivity of excitatory
      neurons during adaptation.

PMID- 29069596
TI  - Suppressed Calbindin Levels in Hippocampal Excitatory Neurons Mediate Stress
      Induced Memory Loss.
AB  - Calbindin modulates intracellular Ca2+ dynamics and synaptic plasticity.
      Reduction of hippocampal calbindin levels has been implicated in early-life
      stress-related cognitive disorders, but it remains unclear how calbindin in
      distinct populations of hippocampal neurons contributes to stress-induced memory
      loss. Here we report that early-life stress suppressed calbindin levels in CA1
      and dentate gyrus (DG) neurons, and calbindin knockdown in adult CA1 or DG
      excitatory neurons mimicked early-life stress-induced memory loss. In contrast,
      calbindin knockdown in CA1 interneurons preserved long-term memory even after an
      acute stress challenge. These results indicate that the dysregulation of
      calbindin in hippocampal excitatory, but not inhibitory, neurons conveys
      susceptibility to stress-induced memory deficits. Moreover, calbindin levels were
      downregulated by early-life stress through the corticotropin-releasing hormone
      receptor 1-nectin3 pathway, which in turn reduced inositol monophosphatase
      levels. Our findings highlight calbindin as a molecular target of early-life
      stress and an essential substrate for memory.

PMID- 29069597
TI  - Adaptive Control of Dorsal Raphe by 5-HT4 in the Prefrontal Cortex Prevents
      Persistent Hypophagia following Stress.
AB  - Transient reduced food intake (hypophagia) following high stress could have
      beneficial effects on longevity, but paradoxically, hypophagia can persist and
      become anorexia-like behavior. The neural underpinnings of stress-induced
      hypophagia and the mechanisms by which the brain prevents the transition from
      transient to persistent hypophagia remain undetermined. In this study, we report
      the involvement of a network governing goal-directed behavior (decision). This
      network consists of the ascending serotonergic inputs from the dorsal raphe
      nucleus (DR) to the medial prefrontal cortex (mPFC). Specifically, adult
      restoration of serotonin 4 receptor (5-HT4R) expression in the mPFC rescues
      hypophagia and specific molecular changes related to depression resistance in the
      DR (5-HT release elevation, 5-HT1A receptor, and 5-HT transporter reductions) of
      stressed 5-HT4R knockout mice. The adult mPFC-5-HT4R knockdown mimics the null
      phenotypes. When mPFC-5-HT4Rs are overexpressed and DR-5-HT1ARs are blocked in
      the DR, hypophagia following stress persists, suggesting an antidepressant action
      of early anorexia.

PMID- 29069598
TI  - Brain-wide Mapping of Endogenous Serotonergic Transmission via Chemogenetic fMRI.
AB  - Serotonin-producing neurons profusely innervate brain regions via long-range
      projections. However, it remains unclear whether and how endogenous serotonergic
      transmission specifically influences regional or global functional activity. We
      combined designed receptors exclusively activated by designed drugs (DREADD)
      based chemogenetics and functional magnetic resonance imaging (fMRI), an approach
      we term "chemo-fMRI," to causally probe the brain-wide substrates modulated by
      endogenous serotonergic activity. We describe the generation of a conditional
      knockin mouse line that, crossed with serotonin-specific Cre-recombinase mice,
      allowed us to remotely stimulate serotonergic neurons during fMRI scans. We show
      that endogenous stimulation of serotonin-producing neurons does not affect global
      brain activity but results in region-specific activation of a set of primary
      target regions encompassing corticohippocampal and ventrostriatal areas. By
      contrast, pharmacological boosting of serotonin levels produced widespread fMRI
      deactivation, plausibly reflecting the mixed contribution of central and
      perivascular constrictive effects. Our results identify the primary functional
      targets of endogenous serotonergic stimulation and establish causation between
      activation of serotonergic neurons and regional fMRI signals.

PMID- 29069599
TI  - Volume Conduction Coupling of Whisker-Evoked Cortical LFP in the Mouse Olfactory
      Bulb.
AB  - Local field potentials (LFPs) are an important measure of brain activity and have
      been used to address various mechanistic and behavioral questions. We revealed a
      prominent whisker-evoked LFP signal in the olfactory bulb and investigated its
      physiology. This signal, dependent on barrel cortex activation and highly
      correlated with its local activity, represented a pure volume conduction signal
      that was sourced back to the activity in the ventro-lateral orbitofrontal cortex,
      located a few millimeters away. Thus, we suggest that special care should be
      taken when acquiring and interpreting LFP data.

PMID- 29069600
TI  - A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters Ion
      Selectivity and Causes Epileptic Encephalopathy.
AB  - Early infantile epileptic encephalopathies (EOEE) are a debilitating spectrum of
      disorders associated with cognitive impairments. We present a clinical report of
      a KCNT2 mutation in an EOEE patient. The de novo heterozygous variant Phe240Leu
      SLICK was identified by exome sequencing and confirmed by Sanger sequencing.
      Phe240Leu rSlick and hSLICK channels were electrophysiologically, heterologously
      characterized to reveal three significant alterations to channel function. First,
      [Cl-]i sensitivity was reversed in Phe240Leu channels. Second, predominantly K+
      selective WT channels were made to favor Na+ over K+ by Phe240Leu. Third, and
      consequent to altered ion selectivity, Phe240Leu channels had larger inward
      conductance. Further, rSlick channels induced membrane hyperexcitability when
      expressed in primary neurons, resembling the cellular seizure phenotype. Taken
      together, our results confirm that Phe240Leu is a "change-of-function" KCNT2
      mutation, demonstrating unusual altered selectivity in KNa channels. These
      findings establish pathogenicity of the Phe240Leu KCNT2 mutation in the reported
      EOEE patient.

PMID- 29069601
TI  - Thymospheres Are Formed by Mesenchymal Cells with the Potential to Generate
      Adipocytes, but Not Epithelial Cells.
AB  - Evidence suggests that a stem-cell-driven differentiation hierarchy maintains the
      dynamic thymic epithelial cell (TEC) network that governs T lymphocyte
      development. The identification of TEC stem/progenitor cells has been a major
      focus in the field, and several candidates with contrasting phenotypes have been
      described. We sought to determine the provenance and function of the only
      population reported to exhibit TEC stem cell properties in the adult, a Foxn1-
      EpCAM- cell that generates so-called thymospheres. We provide evidence that the
      thymosphere-forming cell (TSFC) is not a TEC stem cell but can incorporate
      bystander TECs into thymospheres, providing an explanation for the epithelial
      activity ascribed to these structures. TSFCs were found to share a phenotype,
      transcriptional profile, and developmental origin with thymic fibroblasts and can
      generate adipocytes. In summary, this study redefines the nature of bipotent TEC
      stem/progenitor cells in the adult thymus and highlights a potentially important
      mesenchymal progenitor population.

PMID- 29069602
TI  - The Histone Variant H2A.Z Is a Master Regulator of the Epithelial-Mesenchymal
      Transition.
AB  - Epithelial-mesenchymal transition (EMT) is a profound example of cell plasticity
      that is crucial for embryonic development and cancer. Although it has long been
      suspected that chromatin-based mechanisms play a role in this process, no master
      regulator that can specifically regulate EMT has been identified to date. Here,
      we show that H2A.Z can coordinate EMT by serving as either an activator or
      repressor of epithelial or mesenchymal gene expression, respectively. Following
      induction of EMT by TGF-beta, we observed an unexpected loss of H2A.Z across both
      downregulated epithelial and upregulated mesenchymal promoters. Strikingly, the
      repression of epithelial gene expression was associated with reduction of H2A.Z
      upstream of the transcription start site (TSS), while the activation of
      mesenchymal gene expression was dependent on removal of H2A.Z downstream of the
      TSS. Therefore, the ability of H2A.Z to regulate EMT is dependent on its
      position, either upstream or downstream of the TSS.

PMID- 29069603
TI  - In Vivo Translatome Profiling in Spinal Muscular Atrophy Reveals a Role for SMN
      Protein in Ribosome Biology.
AB  - Genetic alterations impacting ubiquitously expressed proteins involved in RNA
      metabolism often result in neurodegenerative conditions, with increasing evidence
      suggesting that translation defects can contribute to disease. Spinal muscular
      atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein,
      whose role in pathogenesis remains unclear. Here, we identified in vivo and in
      vitro translation defects that are cell autonomous and SMN dependent. By
      determining in parallel the in vivo transcriptome and translatome in SMA mice, we
      observed a robust decrease in translation efficiency arising during early stages
      of disease. We provide a catalogue of RNAs with altered translation efficiency,
      identifying ribosome biology and translation as central processes affected by SMN
      depletion. This was further supported by a decrease in the number of ribosomes in
      SMA motor neurons in vivo. Overall, our findings suggest ribosome biology as an
      important, yet largely overlooked, factor in motor neuron degeneration.

PMID- 29069614
TI  - Increased biomass and quality and reduced heavy metal accumulation of edible
      tissues of vegetables in the presence of Cd-tolerant and immobilizing Bacillus
      megaterium H3.
AB  - A Cd-resistant and immobilizing Bacillus megaterium H3 was characterized for its
      impact on the biomass and quality and heavy metal uptake of edible tissues of two
      vegetables (Brassica campestris L. var. Aijiaohuang and Brassica rapa L. var.
      Shanghaiqing) grown in heavy metal-polluted soil. The impact of strain H3 on the
      soil quality was also evaluated. The increase in the edible tissue biomass and
      the contents of soluble proteins and vitamin C of the vegetables inoculated with
      strain H3 ranged from 18% to 33%, 17% to 31%, and 15% to 19%, respectively,
      compared with the controls. Strain H3 significantly decreased the edible tissue
      Cd and Pb contents of the two greens (41-80%), DTPA-extractable Cd content (35
      47%) of the rhizosphere soils, and Cd and Pb translocation factors (25-56%) of
      the greens compared with the controls. Moreover, strain H3 significantly
      increased the organic matter content (17-21%) and invertase activity (13-14%) of
      the rhizosphere soils compared with the controls. Our results demonstrated the
      increased edible tissue biomass and quality, decreased Cd and Pb uptake of the
      edible tissues, and improved soil quality in the presence of strain H3. The
      results also suggested an effective bacterial-enhanced technique for decreased
      metal uptake of greens and improved vegetable and soil qualities in the metal
      contaminated soils.

PMID- 29069608
TI  - Uev1A-Ubc13 catalyzes K63-linked ubiquitination of RHBDF2 to promote TACE
      maturation.
AB  - The TNFalpha-induced NF-kappaB signaling pathway plays critical roles in multiple
      biological processes. Extensive studies have explored the mechanisms regulating
      this signaling cascade, and identified an E2 complex, Uev1A-Ubc13, that mediates
      K63-linked poly-Ub chain formation and thus recruits NEMO to activate the
      signaling transduction. In this study, we demonstrate that the Uev1A-Ubc13
      complex simultaneously serves as a repressor of the NF-kappaB pathway. It was
      found that cells overexpressing UEV1A silence the signal cascade earlier than
      control cells. Importantly, UEV1A overexpression enhances TACE maturation to shed
      the TNFalpha receptor. The Uev1A-Ubc13 complex interacts with RHBDF2, a key
      factor promoting TACE maturation, and inhibition of the Uev1A-Ubc13 activity
      interferes with RHBDF2-promoted TACE maturation. Furthermore, upon TNFalpha
      stimulation, the Uev1A-Ubc13 complex cooperates with CHIP to promote K63-linked
      ubiquitination of RHBDF2, enhancing its activity toward TACE maturation and
      subsequently blocking TNFalpha-induced NF-kappaB signaling.

PMID- 29069609
TI  - Development of a data independent acquisition mass spectrometry workflow to
      enable glycopeptide analysis without predefined glycan compositional knowledge.
AB  - : Glycoproteomics investigates glycan moieties in a site specific manner to
      reveal the functional roles of protein glycosylation. Identification of
      glycopeptides from data-dependent acquisition (DDA) relies on high quality MS/MS
      spectra of glycopeptide precursors and often requires manual validation to ensure
      confident assignments. In this study, we investigated pseudo-MRM (MRM-HR) and
      data-independent acquisition (DIA) as alternative acquisition strategies for
      glycopeptide analysis. These approaches allow data acquisition over the full
      MS/MS scan range allowing data re-analysis post-acquisition, without data re
      acquisition. The advantage of MRM-HR over DDA for N-glycopeptide detection was
      demonstrated from targeted analysis of bovine fetuin where all three N
      glycosylation sites were detected, which was not the case with DDA. To overcome
      the duty cycle limitation of MRM-HR acquisition needed for analysis of complex
      samples such as plasma we trialed DIA. This allowed development of a targeted DIA
      method to identify N-glycopeptides without pre-defined knowledge of the glycan
      composition, thus providing the potential to identify N-glycopeptides with
      unexpected structures. This workflow was demonstrated by detection of 59 N
      glycosylation sites from 41 glycoproteins from a HILIC enriched human plasma
      tryptic digest. 21 glycoforms of IgG1 glycopeptides were identified including two
      truncated structures that are rarely reported. SIGNIFICANCE: We developed a data
      independent mass spectrometry workflow to identify specific glycopeptides from
      complex biological mixtures. The novelty is that this approach does not require
      glycan composition to be pre-defined, thereby allowing glycopeptides carrying
      unexpected glycans to be identified. This is demonstrated through the analysis of
      immunoglobulins in human plasma where we detected two IgG1 glycoforms that are
      rarely observed.

PMID- 29069610
TI  - New genetic lineage within the Siberian subtype of tick-borne encephalitis virus
      found in Western Siberia, Russia.
AB  - Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is a
      causative agent of a severe neurological disease. There are three main TBEV
      subtypes: the European (TBEV-Eu), Far Eastern (TBEV-FE), and Siberian (TBEV-Sib).
      Currently, three lineages within TBEV-Sib have been recorded. In this study, the
      genetic and biological characteristics of a new original strain, TBEV-2871,
      isolated in the Novosibirsk province of Western Siberia, Russia were
      investigated. The strain has low neuroinvasiveness in mice. Phylogenetic analysis
      demonstrated that TBEV-2871 belongs to TBEV-Sib, but does not cluster with any of
      the TBEV-Sib lineages. The TBEV-2871 strain has 88-89% nucleotide sequence
      identity with the other TBEV-Sib strains, 84-86% nucleotide sequence identity
      with the TBEV-FE and TBEV-Eu subtypes and is genetically close to the subtype
      division border. The TBEV-2871 polyprotein sequence includes 43 unique amino acid
      substitutions, 30 of which are recorded at positions that are conserved among all
      TBEV subtypes. Strain TBEV-2871 and two similar but not identical isolates found
      in Kemerovo province, Western Siberia are separated into a new lineage
      tentatively named Obskaya after the name of Ob riber, in the vicinity of which
      the TBEV-2871 was first found. A molecular evolution investigation demonstrated
      that within TBEV-Sib, the Obskaya lineage likely separated 1535years ago, which
      is even earlier than the Baltic lineage.

PMID- 29069612
TI  - Accumulation, depuration dynamics and effects of dissolved hexavalent chromium in
      juvenile Japanese medaka (Oryzias latipes).
AB  - We previously demonstrated that chronic exposure to hexavalent chromium (Cr(VI))
      causes a variety of adverse effects in the Japanese medaka (Oryzias latipes). The
      present study investigated the transition of acute to chronic effects by
      assessing the influences of Cr(VI) exposure concentration and exposure duration
      on Cr accumulation and their effects on fish growth and antioxidant physiology.
      Juvenile fish were exposed to 0.05, 0.5, 4 or 8mg/L Cr(VI) for 28 days. Endpoints
      were evaluated on days 3, 7, 14, 21 and 28. In addition, Cr depuration was
      examined for fish from two exposure groups (0.5 and 8mg/L). Chromium accumulation
      was rapid initially, then continued at a slower rate till the end of the exposure
      period without showing signs of reaching a steady state. Depuration patterns
      differed between the two exposure groups, but both reached 50% in 14 days. The
      rapid initial accumulation was accompanied by increased lipid peroxidation and
      elevated activities of antioxidants (e.g., GST, SOD and CAT). Activities of these
      enzymes had mostly returned to baseline levels by day 7, but there was no
      evidence of further cellular damage from ROS. Effects on fish length and weight
      continued to be evident over the 28-day exposure period. Our study suggest that
      the initial effects of Cr(VI) exposure may not be a good predictor of more
      chronic effects in fish as a consequence of an efficient acclimation response by
      the antioxidant system that limits ROS-mediated toxicity.

PMID- 29069613
TI  - Toxic effects of nanomaterial-adsorbed cadmium on Daphnia magna.
AB  - Chemical immobilization technologies involving the use of chemical absorbents
      such as nanomaterials have been recommended for the remediation of Cd
      contaminated water and soil. The impact of nanomaterials or nanomaterials
      coexisting with other contaminants on aquatic organisms has been reported, but
      information on the toxic effects of nanomaterial-adsorbed cadmium (Nano-Cd) on
      aquatic organisms is lacking. This study aimed to investigate the acute and sub
      acute toxicity of Nano-Cd on Daphnia magna by using a method developed based on
      the standard Organisation for Economic Co-operation and Development (OECD) 202
      guidelines. The toxicity of cadmium chloride (Cd2+), nano-manganese dioxide
      cadmium (nMnO2-Cd), 20nm nano-hydroxyapatite-cadmium (nHAP20-Cd), and 40nm nano
      hydroxyapatite-cadmium (nHAP40-Cd) to D. magna was in the following order: Cd2+>
      nMnO2-Cd > nHAP20-Cd > nHAP40-Cd. Further, nMnO2-Cd, nHAP20-Cd, and nHAP40-Cd
      showed acute toxicity to D. magna of level II grade according to the Commission
      of the European Communities and OECD standards. Exposure to low and medium, but
      not high, Nano-Cd concentrations increased the activities of peroxidase,
      superoxide dismutase, catalase, and anti-superoxide anion. Thus, Nano-Cd,
      particularly at high concentrations, could exert oxidative damage in D. magna. An
      increase in Cd2+ and Nano-Cd concentrations gradually increased the
      malondialdehyde content, indicating cell membrane damage caused by the production
      of excessive O2-. Thus, the use of nanomaterials after adsorption of Cd is
      associated with a potential risk to aquatic organisms.

PMID- 29069624
TI  - Patterns of cannabis use and clinical correlates among individuals with Major
      Depressive Disorder and Bipolar Disorder.
AB  - BACKGROUND: Major Depressive Disorder (MDD) and Bipolar Disorder (BPD) are the
      most severe mood disorders globally. Previous reports indicate high co-occurrence
      of cannabis use and cannabis use disorders (CUDs) associated with both disorders,
      yet studies comparing patterns of cannabis use between individuals with MDD and
      BPD are scarce. METHODS: Data were drawn from Wave 1 (2001-2002) of the National
      Epidemiologic survey on Alcohol and Related Conditions (NESARC). Cannabis users
      who qualified for a diagnosis of past-year MDD (N=217) were compared to those
      with BPD (N=168) in frequency and daily dose of cannabis use, rates of comorbid
      psychiatric disorders including specific criteria of CUDs, treatment utilization
      and suicidality. RESULTS: Among past-year cannabis users, individuals with BPD
      reported using cannabis more frequently and smoking more joints per day compared
      to those with MDD. They were also more likely to suffer from comorbid personality
      disorders and qualify for specific CUD-criteria, including use in physically
      hazardous situations and unsuccessful efforts to control substance use.
      CONCLUSIONS: Our results indicate that individuals with BPD may present more
      intensive patterns of cannabis use compared to those with MDD. This may have
      potential effects on the course of BPD and should be further explored in
      longitudinal studies.

PMID- 29069616
TI  - The assessment and treatment of adult heterosexual men with self-perceived
      problematic pornography use: A review.
AB  - Self-Perceived Problematic Porn Use (SPPPU) refers to an individual who self
      identifies as addicted to porn because they feel they are unable to regulate
      their porn consumption, and that use interferes with everyday life. Although porn
      addiction has not been formally classified as its own distinct behavioral
      addiction, therapists and clinicians are advised to educate themselves on the
      current state of literature pertaining to pornography consumption given the
      widespread availability and consumption of sexually explicit material online.
      This review article begins with a general overview of pornography and porn use so
      that therapists and researchers can discern between non-intrusive and problematic
      pornography consumption patterns within their practice and understand the common
      characteristics of those that most commonly present with SPPPU. Thereafter, an
      overview and examination of therapeutic interventions for SPPPU will be
      identified and analysed. Finally, the review concludes with recommendations for
      therapists, clinicians, and future research.

PMID- 29069626
TI  - Paravertebral block for the anesthetic management in a patient with severe
      ankylosing spondylitis: Single injection or multiple injections?

PMID- 29069617
TI  - Development of Brain Network in Children with Autism from Early Childhood to Late
      Childhood.
AB  - Extensive studies have indicated brain function connectivity abnormalities in
      autism spectrum disorder (ASD). However, there is a lack of longitudinal or cross
      sectional research focused on tracking age-related developmental trends of
      autistic children at an early stage of brain development or based on a relatively
      large sample. The present study examined brain network changes in a total of 186
      children both with and without ASD from 3 to 11 years, an early and key
      development period when significant changes are expected. The study aimed to
      investigate possible abnormal connectivity patterns and topological properties of
      children with ASD from early childhood to late childhood by using resting-state
      electroencephalographic (EEG) data. The main findings of the study were as
      follows: (1) From the connectivity analysis, several inter-regional
      synchronizations with reduction were identified in the younger and older ASD
      groups, and several intra-regional synchronization increases were observed in the
      older ASD group. (2) From the graph analysis, a reduced clustering coefficient
      and enhanced mean shortest path length in specific frequencies was observed in
      children with ASD. (3) Results suggested an age-related decrease of the mean
      shortest path length in the delta and theta bands in TD children, whereas
      atypical age-related alteration was observed in the ASD group. In addition, graph
      measures were correlated with ASD symptom severity in the alpha band. These
      results demonstrate that abnormal neural communication is already present at the
      early stages of brain development in autistic children and this may be involved
      in the behavioral deficits associated with ASD.

PMID- 29069606
TI  - Distinct Microbial Communities Trigger Colitis Development upon Intestinal
      Barrier Damage via Innate or Adaptive Immune Cells.
AB  - Inflammatory bowel disease comprises a group of heterogeneous diseases
      characterized by chronic and relapsing mucosal inflammation. Alterations in
      microbiota composition have been proposed to contribute to disease development,
      but no uniform signatures have yet been identified. Here, we compare the ability
      of a diverse set of microbial communities to exacerbate intestinal inflammation
      after chemical damage to the intestinal barrier. Strikingly, genetically
      identical wild-type mice differing only in their microbiota composition varied
      strongly in their colitis susceptibility. Transfer of distinct colitogenic
      communities in gene-deficient mice revealed that they triggered disease via
      opposing pathways either independent or dependent on adaptive immunity,
      specifically requiring antigen-specific CD4+ T cells. Our data provide evidence
      for the concept that microbial communities may alter disease susceptibility via
      different immune pathways despite eventually resulting in similar host pathology.
      This suggests a potential benefit for personalizing IBD therapies according to
      patient-specific microbiota signatures.

PMID- 29069611
TI  - Metabolic modeling helps interpret transcriptomic changes during malaria.
AB  - Disease represents a specific case of malfunctioning within a complex system.
      Whereas it is often feasible to observe and possibly treat the symptoms of a
      disease, it is much more challenging to identify and characterize its molecular
      root causes. Even in infectious diseases that are caused by a known parasite, it
      is often impossible to pinpoint exactly which molecular profiles of components or
      processes are directly or indirectly altered. However, a deep understanding of
      such profiles is a prerequisite for rational, efficacious treatments. Modern
      omics methodologies are permitting large-scale scans of some molecular profiles,
      but these scans often yield results that are not intuitive and difficult to
      interpret. For instance, the comparison of healthy and diseased transcriptome
      profiles may point to certain sets of involved genes, but a host of post
      transcriptional processes and regulatory mechanisms renders predictions regarding
      metabolic or physiological consequences of the observed changes in gene
      expression unreliable. Here we present proof of concept that dynamic models of
      metabolic pathway systems may offer a tool for interpreting transcriptomic
      profiles measured during disease. We illustrate this strategy with the
      interpretation of expression data of genes coding for enzymes associated with
      purine metabolism. These data were obtained during infections of rhesus macaques
      (Macaca mulatta) with the malaria parasite Plasmodium cynomolgi or P. coatneyi.
      The model-based interpretation reveals clear patterns of flux redistribution
      within the purine pathway that are consistent between the two malaria pathogens
      and are even reflected in data from humans infected with P. falciparum. This
      article is part of a Special Issue entitled: Accelerating Precision Medicine
      through Genetic and Genomic Big Data Analysis edited by Yudong Cai & Tao Huang.

PMID- 29069619
TI  - Breakdown of Excitability by Attenuated PRV-152 Infection in Auditory Brainstem
      Neurons of Mongolian Gerbils.
AB  - Pseudorabies virus (PRV), a neurovirulent alpha-herpesvirus, spreads between
      neurons at synaptic connections. PRV-infected neurons have been shown to exhibit
      functional deficits with the attenuated PRV152 Bartha strain negatively
      influencing neuronal functioning in in vitro model systems. However, the impact
      of this attenuated PRV152 Bartha strain on the native central nervous system has
      not been fully explored. Using a combination of in vivo stereotactic injections
      and post-hoc in vitro whole-cell recordings, we investigated the functional
      impact of PRV152 Bartha in the auditory system of juvenile Mongolian gerbils. The
      specificity of this virus strain to spread exclusively trans-synaptically in a
      retrograde fashion and the well-defined structure of the ascending auditory
      brainstem pathways allowed us to determine the physiological alterations in
      primary and secondary infected neurons. We find at primary and secondary
      infections sites, the inferior colliculus (IC) and dorsal nucleus of the lateral
      lemniscus respectively, a reduced excitability of infected cells. The loss of
      excitability is manifested by an increase in current threshold and a loss of
      action potential generation. The minor changes in the approximated passive
      membrane parameters induced by the infection cannot explain the full loss in
      excitability, indicating that channel densities and properties have changed. This
      impact on neuronal functioning might contribute to the lethal neurovirulent
      effects of PRV viruses as vital neuronal circuits might cease activity. Since the
      detrimental effects of the attenuated PRV152 Bartha strain are reduced compared
      to wild-type strains, it comprises an excellent tool to study the
      neuropathological mechanisms of viral infections.

PMID- 29069618
TI  - Blockade of Interleukin-7 Receptor Shapes Macrophage Alternative Activation and
      Promotes Functional Recovery After Spinal Cord Injury.
AB  - Macrophages are implicated in the pathological processes and functional recovery
      of spinal cord injury (SCI). Macrophage activation following inflammation depends
      on networks of interferons and cytokines. Recent evidence indicate that IL-7
      signaling can influence the release of proinflammatory factors, however, its
      roles in modulating macrophage phenotype and function and whether it could affect
      the functional recovery of SCI are poorly understood. Here, we show that, in a
      murine SCI model, IL-7 is promptly and vastly induced in injured spinal cord, and
      that blockade of IL-7 signaling with anti-IL-7Ralpha mAb (A7R34) favors the
      generation of M2 phenotype macrophages by affecting the cytokine productions in T
      helper (Th)1 and Th2 cells. Furthermore, IL-7 displays strong chemotactic
      property for macrophages and A7R34 treatment inhibits their infiltration into
      injured sites in vivo. More importantly, the A7R34 treatment promotes functional
      recovery after SCI, indicating its therapeutic effects on spinal cord repair.
      Hence, our study proposes a new therapeutic strategy to treat SCI by blocking IL
      7 signaling.

PMID- 29069607
TI  - Prenatal methamphetamine exposure is associated with reduced subcortical volumes
      in neonates.
AB  - OBJECTIVES: Prenatal exposure to methamphetamine is associated with a range of
      neuropsychological, behavioural and cognitive deficits. A small number of imaging
      studies suggests that these may be mediated by neurostructural changes, including
      reduced volumes of specific brain regions. This study investigated potential
      volumetric changes in the brains of neonates with prenatal methamphetamine
      exposure. To our knowledge no previous studies have examined methamphetamine
      effects on regional brain volumes at this age. STUDY DESIGN: Mothers were
      recruited antenatally and interviewed regarding methamphetamine use during
      pregnancy. Mothers in the exposure group reported using
      methamphetamine>=twice/month during pregnancy; control infants had no exposure to
      methamphetamine or other drugs and minimal exposure to alcohol. MRI scans were
      performed in the first postnatal month, following which anatomical images were
      processed using FreeSurfer. Subcortical and cerebellar regions were manually
      segmented and their volumes determined using FreeView. Pearson correlations were
      used to analyse potential associations between methamphetamine exposure and
      regional volumes. The associations between methamphetamine exposure and regional
      volumes were then examined adjusting for potential confounding variables.
      RESULTS: Methamphetamine exposure was associated with reduced left and right
      caudate and thalamus volumes. The association in the right caudate remained
      significant following adjustment for potential confounding variables.
      CONCLUSIONS: Our findings showing reduced caudate and thalamus volumes in
      neonates with prenatal methamphetamine exposure are consistent with previous
      findings in older exposed children, and demonstrate that these changes are
      already detectable in neonates. Continuing research is warranted to examine
      whether reduced subcortical volumes are predictive of cognitive, behavioural and
      affective impairment in older children.

PMID- 29069620
TI  - Propofol Protects Rat Hypoglossal Motoneurons in an In Vitro Model of
      Excitotoxicity by Boosting GABAergic Inhibition and Reducing Oxidative Stress.
AB  - In brainstem motor networks, hypoglossal motoneurons (HMs) play the physiological
      role of driving tongue contraction, an activity critical for inspiration,
      phonation, chewing and swallowing. HMs are an early target of neurodegenerative
      diseases like amyotrophic lateral sclerosis that, in its bulbar form, is
      manifested with initial dysphagia and dysarthria. One important pathogenetic
      component of this disease is the high level of extracellular glutamate due to
      uptake block that generates excitotoxicity. To understand the earliest phases of
      this condition we devised a model, the rat brainstem slice, in which block of
      glutamate uptake is associated with intense bursting of HMs, dysmetabolism and
      death. Since blocking bursting becomes a goal to prevent cell damage, the present
      report enquired whether boosting GABAergic inhibition could fulfill this aim and
      confer beneficial outcome. Propofol (0.5 uM) and midazolam (0.01 uM), two
      allosteric modulators of GABAA receptors, were used at concentrations yielding
      analogous potentiation of GABA-mediated currents. Propofol also partly depressed
      NMDA receptor currents. Both drugs significantly shortened bursting episodes
      without changing single burst properties, their synchronicity, or their
      occurrence. Two hours later, propofol prevented the rise in reactive oxygen
      species (ROS) and, at 4 hours, it inhibited intracellular release of apoptosis
      inducing factor (AIF) and prevented concomitant cell loss. Midazolam did not
      contrast ROS and AIF release. The present work provides experimental evidence for
      the neuroprotective action of a general anesthetic like propofol, which, in this
      case, may be achieved through a combination of boosted GABAergic inhibition and
      reduced ROS production.

PMID- 29069615
TI  - The role of late life depressive symptoms on the trajectories of insomnia
      symptoms during antidepressant treatment.
AB  - OBJECTIVE: Sleep disturbances are common in late life depression; however,
      changes in insomnia symptoms during antidepressant treatment need to be
      characterized further. The objective of this study was two-fold: 1) to describe
      longitudinal trajectories of insomnia symptoms in older adults receiving
      antidepressant treatment and 2) to examine whether baseline depressive symptoms
      were associated with trajectories of sleep over time. METHODS: Data was obtained
      from 680 older adults (aged >= 60) with major depression who participated in one
      of two protocolized open-label antidepressant treatment clinical trials
      (Maintenance Therapies in Late Life Depression [MTLD-3]; Incomplete Response in
      Late Life Depression: Getting to Remission [IRL-GRey]). Depression (total score
      minus sleep items) and sleep (sum of sleep items) outcomes were derived from the
      Hamilton Depression Rating Scale in the MLTD-3 and Montgomery-Asberg Depression
      Rating Scale in the IRL-GRey. RESULTS: Both datasets identified 5 possible
      trajectories of insomnia symptoms with about half of the older adults having
      clinically significant baseline sleep disturbances and minimal improvement
      following a course of antidepressant treatment (i.e., sub-optimal sleep
      trajectory). Furthermore, across both datasets, worse baseline depression
      severity was associated with sub-optimal sleep trajectories. CONCLUSION: In older
      adults receiving antidepressant treatment, those with clinically significant
      baseline sleep disturbances and greater depression severity may require
      adjunctive sleep-focused treatment to ameliorate sleep symptoms.

PMID- 29069621
TI  - Anticipated pleasure for positive and negative social interaction outcomes in
      schizophrenia.
AB  - While recent research suggests that people with schizophrenia anticipate less
      pleasure for non-social events, considerably less is known about anticipated
      pleasure for social events. In this study, we investigated whether people with
      and without schizophrenia differ in the amount and updating of anticipated
      pleasure over the course of repeated interactions as well as the influence of
      emotional displays. Thirty-two people with schizophrenia and 29 controls rated
      their anticipated pleasure over the course of repeated interactions with smiling,
      scowling, or neutral social partners that had either positive or negative
      outcomes. Compared to controls, people with schizophrenia anticipated a lower
      amount of pleasure during interactions with smiling, but not neutral social
      partners that had positive outcomes. However, the groups did not differ in the
      amount or updating of anticipated pleasure during interactions that had negative
      outcomes. Both groups anticipated more pleasure over the course of repeated
      interactions with smiling partners and less pleasure over the course of repeated
      interactions with scowling partners compared to interactions with neutral
      partners. We discuss how less anticipated pleasure for interactions with smiling
      social partners may be linked to difficulties in social engagement among people
      with schizophrenia.

PMID- 29069628
TI  - Still lonely: Social adjustment of youth with and without social anxiety disorder
      following cognitive behavioral therapy.
AB  - Social experiences are an integral part of normative development for youth and
      social functioning difficulties are related to poor outcomes. Youth with anxiety
      disorders, and particularly social anxiety disorder, experience difficulties
      across many aspects of social functioning that may place them at risk for
      maladjustment. The goal of this paper was to compare social experiences of youth
      across anxiety diagnoses and examine whether treatment is helpful in improving
      social functioning. Ninety-two children (age 7-12 years; 58% male; 87.0% White)
      with a primary diagnosis of generalized anxiety disorder, separation anxiety
      disorder, and/or social anxiety disorder participated in cognitive behavioral
      therapy. At both pre- and post-treatment, children with social anxiety disorder
      self-reported greater loneliness than youth without social anxiety disorder,
      though levels of peer victimization and receipt of prosocial behavior were
      similar across groups. Parents reported greater social problems for youth with
      social anxiety disorder compared to those without social anxiety disorder. All
      youth experienced improved social functioning following treatment per child- and
      parent-reports. The results call for an increased focus on the social experiences
      of youth with anxiety disorders, and particularly loneliness, for children with
      social anxiety disorder. The results document ways that evidenced-based practice
      can improve social functioning for youth with anxiety disorders.

PMID- 29069622
TI  - Intramuscular delivery of replication-defective herpes simplex virus gives
      antigen expression in muscle syncytia and improved protection against pathogenic
      HSV-2 strains.
AB  - Herpes simplex virus 2 (HSV-2) is the leading cause of genital herpes and
      increases the risk of HIV infection, but there is no effective vaccine. A
      replication-defective HSV-2 mutant virus, dl5-29, is effective in animal models
      and has been in a phase I trial. Previous studies have shown that dl5-29 gives
      higher antibody responses and better protection when inoculated intramuscularly
      (IM) as compared with subcutaneously (SC). However, the basis for this effect has
      not been defined. We confirmed that IM inoculation of dl5-29 is more immunogenic
      and provides better protection than SC inoculation. IM inoculation of HSV-2
      strains produced higher levels of a luciferase transgene than SC inoculation, as
      measured by intravital bioluminescence imaging. Intramuscular immunization also
      showed better protection against infection with a highly pathogenic African HSV
      2, demonstrating that this single vaccine can be efficacious against HSV-2
      strains from different geographic regions.

PMID- 29069605
TI  - The Conserved ATM Kinase RAG2-S365 Phosphorylation Site Limits Cleavage Events in
      Individual Cells Independent of Any Repair Defect.
AB  - Many DNA lesions associated with lymphoid malignancies are linked to off-target
      cleavage by the RAG1/2 recombinase. However, off-target cleavage has mostly been
      analyzed in the context of DNA repair defects, confounding any mechanistic
      understanding of cleavage deregulation. We identified a conserved SQ
      phosphorylation site on RAG2 365 to 366 that is involved in feedback control of
      RAG cleavage. Mutation of serine 365 to a non-phosphorylatable alanine permits bi
      allelic and bi-locus RAG-mediated breaks in the same cell, leading to reciprocal
      translocations. This phenomenon is analogous to the phenotype we described for
      ATM kinase inactivation. Here, we establish deregulated cleavage itself as a
      driver of chromosomal instability without the associated repair defect.
      Intriguingly, a RAG2-S365E phosphomimetic rescues the deregulated cleavage of ATM
      inactivation, reducing the incidence of reciprocal translocations. These data
      support a model in which feedback control of cleavage and maintenance of genome
      stability involves ATM-mediated phosphorylation of RAG2.

PMID- 29069625
TI  - Clinical utility of the DSM-5 alternative model for borderline personality
      disorder: Differential diagnostic accuracy of the BFI, SCID-II-PQ, and PID-5.
AB  - BACKGROUND: With the publication of DSM 5 alternative model for personality
      disorders it is critical to assess the components of the model against evidence
      based models such as the five factor model and the DSM-IV-TR categorical model.
      This study explored the relative clinical utility of these models in screening
      for borderline personality disorder (BPD). METHODS: Receiver operator
      characteristics and diagnostic efficiency statistics were calculated for three
      personality measures to ascertain the relative diagnostic efficiency of each
      measure. A total of 1653 adult inpatients at a specialist psychiatric hospital
      completed SCID-II interviews. Sample 1 (n=653) completed the SCID-II interviews,
      SCID-II Questionnaire (SCID-II-PQ) and the Big Five Inventory (BFI), while Sample
      2 (n=1,000) completed the SCID-II interviews, Personality Inventory for DSM5 (PID
      5) and the BFI. RESULTS: BFI measure evidenced moderate accuracy for two
      composites: High Neuroticism+ low agreeableness composite (AUC=0.72, SE=0.01,
      p<0.001) and High Neuroticism+ Low+Low Conscientiousness (AUC=0.73, SE=0.01,
      p<0.0001). The SCID-II-PQ evidenced moderate-to-excellent accuracy (AUC=0.86,
      SE=0.02, p<0.0001) with a good balance of specificity (SP=0.80) and sensitivity
      (SN=0.78). The PID-5 BPD algorithm (consisting of elevated emotional lability,
      anxiousness, separation insecurity, hostility, depressivity, impulsivity, and
      risk taking) evidenced moderate-to-excellent accuracy (AUC=0.87, SE=0.01,
      p<0.0001) with a good balance of specificity (SP=0.76) and sensitivity (SN=0.81).
      CONCLUSIONS: Findings generally support the use of SCID-II-PQ and PID-5 BPD
      algorithm for screening purposes. Furthermore, findings support the accuracy of
      the DSM 5 alternative model Criteria B trait constellation for diagnosing BPD.
      Limitations of the study include the single inpatient setting and use of two
      discrete samples to assess PID-5 and SCID-II-PQ.

PMID- 29069630
TI  - Effects of Pu-erh ripened tea on hyperuricemic mice studied by serum
      metabolomics.
AB  - To evaluate effects of Pu-erh ripened tea in hyperuricemic mice, a mouse
      hyperuricemia model was developed by oral administration of potassium oxonate for
      7 d. Serum metabolomics, based on gas chromatography-mass spectrometry, was used
      to generate metabolic profiles from normal control, hyperuricemic and allopurinol
      treated hyperuricemic mice, as well as hyperuricemic mice given Pu-erh ripened
      tea at three doses. Pu-erh ripened tea significantly lowered serum uric acid
      levels. Twelve potential biomarkers associated with hyperuricemia were
      identified. Pu-erh ripened tea and allopurinol differed in their metabolic
      effects in the hyperuricemic mice. Levels of glutamic acid, indolelactate, L
      allothreonine, nicotinoylglycine, isoleucine, l-cysteine and glycocyamine, all
      involved in amino acid metabolism, were significantly changed in hyperuricemic
      mice treated Pu-erh ripened tea. Thus, modulating amino acid metabolism might be
      the primary mechanism of anti-hyperuricemia by Pu-erh ripened tea.

PMID- 29069629
TI  - Choices of capture chromatography technology in antibody manufacturing processes.
AB  - The capture process employed in monoclonal antibody downstream purification is
      not only the most critically impacted process by increased antibody titer
      resulting from optimized mammalian cell culture expression systems, but also the
      most important purification step in determining overall process throughput,
      product quality, and economics. Advances in separation technology for capturing
      antibodies from complex feedstocks have been one focus of downstream purification
      process innovation for past 10 years. In this study, we evaluated new generation
      chromatography resins used in the antibody capture process including Protein A,
      cation exchange, and mixed mode chromatography to address the benefits and unique
      challenges posed by each chromatography approach. Our results demonstrate the
      benefit of improved binding capacity of new generation Protein A resins, address
      the concern of high concentration surge caused aggregation when using new
      generation cation exchange resins with over 100mg/mL binding capacity, and
      highlight the potential of multimodal cation exchange resins for capture process
      design. The new landscape of capture chromatography technologies provides options
      to achieve overall downstream purification outcome with high product quality and
      process efficiency.

PMID- 29069604
TI  - Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor
      Progression and Marker Expression.
AB  - The cell of origin of pancreatic ductal adenocarcinoma (PDAC) has been
      controversial. Here, we show that identical oncogenic drivers trigger PDAC
      originating from both ductal and acinar cells with similar histology but with
      distinct pathophysiology and marker expression dependent on cell of origin.
      Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by
      pancreatic intraepithelial neoplasias (PanINs), duct-derived tumors displayed
      high AGR2 and developed independently of a PanIN stage via non-mucinous lesions.
      Using orthotopic transplantation and chimera experiments, we demonstrate that
      PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy
      tissues, explaining the co-existence of mucinous and non-mucinous lesions and
      highlighting the need to distinguish between true precursor PanINs and PanIN-like
      bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according
      to cell of origin, highlight that not all PanIN-like lesions are precursors of
      PDAC, and add an alternative progression route to the current model of PDAC
      development.

PMID- 29069631
TI  - Biophysical analysis of BMV virions purified using a novel method.
AB  - Brome mosaic virus (BMV) has been successfully loaded with different types of
      nanoparticles. However, studies concerning its application as a nanoparticle
      carrier demand high-purity virions in large amounts. Existing BMV purification
      protocols rely on multiple differential ultracentrifugation runs of the initially
      purified viral preparation. Herein, we describe an alternative method for BMV
      purification based on ion-exchange chromatography and size-exclusion
      chromatography (SEC) yielding 0.2mg of virus from 1g of plant tissue. Our method
      is of similar efficiency to previously described protocols and can easily be
      scaled up. The method results in high-quality BMV preparations as confirmed by
      biophysical analyses, including cryogenic transmission electron microscopy (cryo
      TEM), dynamic light scattering (DLS), static light scattering (SLS), and circular
      dichroism (CD) measurements and attenuated total reflection Fourier transform
      infrared spectroscopy (ATR-FTIR) spectroscopy. Our results revealed that purified
      BMV capsids are stable and monodisperse and can be used for further downstream
      applications. In this work, we also characterize secondary structure and size
      fluctuations of the BMV virion at different pH values.

PMID- 29069633
TI  - Bioreduction potentials of dried root of Zingiber officinale for a simple green
      synthesis of silver nanoparticles: Antibacterial studies.
AB  - Green synthesis of silver nanoparticles (Ag NPs) using an extract of dried
      Zingiber officinale (ginger) root as a reducing and capping agent in the presence
      of microwave irradiation was herein reported for the first time. The formation of
      symmetrical spheres is confirmed from the UV-Visible spectrum of Ag NPs. Fourier
      transform infra-red spectroscopy confirms the formation of the Ag NPs. X-ray
      diffraction analysis was utilized to calculate the crystallite size of Ag NPs and
      the value was found to be 10nm. High-resolution transmission electron microscopy
      and high-resolution scanning electron microscopy were used to investigate the
      morphology and size of the synthesized samples. The sphere like morphology is
      confirmed from the images. The purity and crystallinity of Ag NPs is confirmed by
      energy-dispersive X-Ray analysis and selected area electron diffraction
      respectively. The electrochemical behavior of the synthesized Ag NPs was assessed
      by cyclic voltammetry (CV) and shows the redox peaks in the potential range of 
      1.1 to +1.1V. Agar diffusion method is used to examine the antibacterial activity
      of Ag NPs. For this purpose, two gram positive and two gram negative bacteria
      were studied. This single step approach was found to be simple, short time, cost
      effective, reproducible, and eco-friendly.

PMID- 29069623
TI  - The effect of impaired verbal memory retrieval on autobiographical memory across
      different life periods in schizophrenia.
AB  - OBJECTIVES: Autobiographical memory (AM) involves recollection of personal events
      and facts about one's life. Alphaim of the present study was to investigate AM in
      schizophrenia patients, and, in particular, patients' ability to recall
      autobiographical memories after controlling for verbal memory and verbal fluency
      deficits. METHOD: Participants included 40 schizophrenia patients (23 male) and
      40 healthy controls (23 male), matched for age, gender, educational level, and
      premorbid intellectual functioning. Participants' verbal memory (list learning
      and story recall) and verbal fluency were assessed. AM was evaluated by the
      Questionnaire of Autobiographical Memory, consisting of the Personal Semantic
      Memory scale and the Autobiographical Incidents scale. Furthermore, personal
      incidents' specificity was examined. RESULTS: Schizophrenia patients showed
      deficits in verbal memory and verbal fluency, as well as in both semantic and
      episodic AM compared with healthy controls. Deficits were shown in episodic and
      semantic memories of events and facts dating to three different life periods
      (childhood, early adulthood and recent life). Regarding specificity of recalled
      events, patients reported fewer specific autobiographical incidents than
      controls. After controlling AM deficits for patients' verbal memory and verbal
      fluency impairment, it was shown that schizophrenia patients recalled fewer
      memories of autobiographical incidents dating only to recent life, compared with
      healthy controls. CONCLUSIONS: Schizophrenia patients showed impaired AM after
      controlling for verbal memory and verbal fluency impairment only in regard with
      personal episodic memories from recent life. Current findings raise the important
      issue of cognitive remediation therapy in schizophrenia.

PMID- 29069632
TI  - Investigation on effect of basalin coated silver nanoparticles as antioxidant for
      alleviating peripheral neuropathy in mice treated with oxaliplatin.
AB  - A facile, convenient, and green method for the synthesis of BAgNPs by using
      basalin is proposed in this work. The capping of the basalin on the surface of
      BAgNP was confirmed by the zeta potential and FTIR findings. Further, we have
      injected prepared BAgNPs into oxaliplatin-treated mice to alleviate neuropathic
      pain. The aluminum levels in the DRG were reduced by the chelating activity of
      BAgNPs. Moreover, behavioral analyses also manifested that the accumulation of
      aluminum on the DRG might be a reason for neuropathic hyperalgesia. These
      findings also recommended that the chelation of aluminum by AgNPs could provide
      an effective remedy to alleviate the symptoms of oxaliplatin-induced neuropathic
      pain in cancer patients.

PMID- 29069634
TI  - Comparing non-invasive scapular tracking methods across elevation angles, planes
      of elevation and humeral axial rotations.
AB  - Altered scapular motions premeditate shoulder impingement and other
      musculoskeletal disorders. Divergent experimental conditions in previous research
      precludes rigorous comparisons of non-invasive scapular tracking techniques. This
      study evaluated scapular orientation measurement methods across an expanded range
      of humeral postures. Scapular medial/lateral rotation, anterior/posterior tilt
      and protraction/retraction was measured using an acromion marker cluster (AMC), a
      scapular locator, and a reference stylus. Motion was captured using reflective
      markers on the upper body, as well as on the AMC, locator and stylus. A
      combination of 5 arm elevation angles, 3 arm elevation planes and 3 arm axial
      rotations was examined. Measurement method interacted with elevation angle and
      plane of elevation for all three scapular orientation directions (p < 0.01).
      Method of measurement interacted with axial rotation in anterior/posterior tilt
      and protraction/retraction (p < 0.01). The AMC had strong agreement with the
      reference stylus than the locator for the majority of humeral elevations, planes
      and axial rotations. The AMC underestimated lateral rotation, with the largest
      difference of ~2 degrees  at 0 degrees  elevation. Both the locator and AMC
      overestimated posterior tilt at high arm elevation by up to 7.4 degrees .
      Misestimations from using the locator could be enough to potentially obscure
      meaningful differences in scapular rotations.

PMID- 29069627
TI  - Src SUMOylation Inhibits Tumor Growth Via Decreasing FAK Y925 Phosphorylation.
AB  - Src, a non-receptor tyrosine kinase protein, plays a critical role in cell
      proliferation and tumorigenesis. SUMOylation, a reversible ubiquitination-like
      post-translational modification, is vital for tumor progression. Here, we report
      that the Src protein can be SUMOylated at lysine 318 both in vitro and in vivo.
      Hypoxia can induce a decrease of Src SUMOylation along with an increase of Y419
      phosphorylation, a phosphorylation event required for Src activation. On the
      other hand, treatment with hydrogen peroxide can enhance Src SUMOylation.
      Significantly, ectopic expression of SUMO-defective mutation, Src K318R, promotes
      tumor growth more potently than that of wild-type Src, as determined by migration
      assay, soft agar assay, and tumor xenograft experiments. Consistently, Src
      SUMOylation leads to a decrease of Y925 phosphorylation of focal adhesion kinase
      (FAK), an established regulatory event of cell migration. Our results suggest
      that SUMOylation of Src at lysine 318 negatively modulate its oncogenic function
      by, at least partially, inhibiting Src-FAK complex activity.

PMID- 29069635
TI  - Pyrolysis of marine biomass to produce bio-oil and its upgrading using a novel
      multi-metal catalyst prepared from the spent car catalytic converter.
AB  - In order to reduce the economic and environmental consequences caused by spent
      car catalyst, we herein report for the first time a novel promising multi-metal
      catalyst prepared from spent car catalytic converters to upgrade the pyrolysis
      bio-oils. The physico-chemical properties of prepared catalyst were characterized
      by XRD, EDS, FESEM, and FT-IR analyses. The thermal stability of the multi-metal
      catalyst was studied with TGA. To investigate the activity of the catalyst,
      Conversion of Cladophora glomerata (C. glomerata) into bio-products was carried
      out via a fixed bed reactor with and without catalyst at the temperature of 500
      degrees C. Although the catalyst didn't catalyze the gasification reaction, bio
      oil was upgraded over the catalyst. The main effect of the catalyst on the bio
      oil components is deoxygenating of nitrogen compounds and promotion the
      ketonization reaction, which converts acid to ketone and declines the corrosive
      nature of bio-oil.

PMID- 29069642
TI  - Abstracts of the 14th Annual ENETS Conference for the Diagnosis and Treatment of
      Neuroendocrine Tumor Disease. March 8-10, 2017, Barcelona, Spain: Abstracts.

PMID- 29069636
TI  - Development and in vitro validation of a simplified numerical model for the
      design of a biomimetic femoral stem.
AB  - BACKGROUND: Dense and stiff metallic femoral stems implanted into femurs for
      total hip arthroplasties produce a stress shielding effect since they modify the
      original load sharing path in the bony structure. Consequently, in the long term,
      the strain adaptive nature of bones leads to bone resorption, implant loosening,
      and the need for arthroplasty revision. The design of new cementless femoral
      stems integrating open porous structures can reduce the global stiffness of the
      stems, allowing them a better match with that of bones and provide their firm
      fixation via bone ingrowth, and, thus reduce the risk of implantation failure.
      METHODS: This paper aims to develop and validate a simplified numerical model of
      stress shielding, which calculates the levels of bone resorption or formation by
      comparing strain distributions on the surface of the intact and the implanted
      femurs subjected to a simulated biological loading. Two femoral stems produced by
      laser powder-bed fusion using Ti-6Al-4V alloy are employed: the first is fully
      dense, while the second features a diamond cubic lattice structure in its core.
      The validation consists of a comparison of the numerically calculated force
      displacement diagrams, and displacement and strain fields with their experimental
      equivalents obtained using the digital image correlation technique. RESULTS AND
      CONCLUSIONS: The numerical models showed reasonable agreement between the force
      displacement diagrams. Also, satisfactory results for the correlation analyses of
      the total displacement and equivalent strain fields were obtained. The stress
      shielding effect of the implant was assessed by comparing the equivalent strain
      fields of the implanted and intact femurs. The results obtained predicted less
      bone resorption in the femur implanted with the porous stem than with its dense
      counterpart.

PMID- 29069638
TI  - The excited-state intramolecular proton transfer in NH-type dye molecules with a
      seven-membered-ring intramolecular hydrogen bond: A theoretical insight.
AB  - Excited-state intramolecular proton transfer (ESIPT) reactions of a series of
      N(R)H?N-type seven-membered-ring hydrogen-bonding compounds were explored by
      employing density functional theory/time-dependent density functional theory
      calculations with the PBE0 functional. Our results indicate that the absorption
      and emission spectra predicted theoretically match very well the experimental
      findings. Additionally, as the electron-withdrawing strength of R increases, the
      intramolecular H-bond of the NS1 form gradually enhances, and the forward energy
      barrier along the ESIPT reaction gradually decreases. For compound 4, its ESIPT
      reaction is found to be a barrierless process due to the involvement of a strong
      electron-withdrawing COCF3 group. It is therefore a reasonable presumption that
      the ESIPT efficiency of these N(R)H?N-type seven-membered-ring H-bonding systems
      can be improved when a strong electron-withdrawing group in R is introduced.

PMID- 29069644
TI  - Interactive Effects of Snps Located Within CD28/B7Pathway and Environment on
      Susceptibility to Recurrent Spontaneous Abortion.
AB  - AIMS: This study was aimed to explore the interaction between environment and
      CD28/B7 pathway to provide the potential epidemiology for prevention and
      treatment of recurrent spontaneous abortion (RSA). METHODS: The retrospective
      study included 630 RSA cases and 1320 healthy women during their middle and late
      prenatal care. Their living environment was investigated, and the influence of
      environmental factors on pregnancy abortion was analyzed. The genomic DNAs were
      extracted from the study subjects, and the polymorphisms of CD28 and B7 were
      analyzed. Finally, the interaction of gene and environment on RSA was analyzed
      with the logistic regression analyses. RESULTS: The multi-variate regression
      analysis indicated that vitamin supplement, intake of fresh fruits or vegetables,
      night shift, staying up late, history miscarriage, as well as history induced
      abortion were, independently, risk factors for RSA (all P< 0.05). Moreover,
      rs3116496 (T>C), rs3181098 (G>A) and rs3181100 (G>C) of CD28, rs1915087 (C>T) of
      B7-2, as well as rs6804441 (A>G) and rs41271391 (G>T) of B7-1 were correlated
      with modified RSA risk (all P< 0.05). The haplotypes TGT and TAG could also
      regulate the risk of RSA (both P< 0.05). The synthetic influences of the
      aforementioned SNPs and environmental factors could also significantly affect the
      susceptibility to RSA (all P< 0.05). CONCLUSION: The interaction of environment
      and SNPs of CD28/B7 pathway on RSA risk was distinct from CD28/B7 pathway or
      environment alone.

PMID- 29069645
TI  - Organized Cervical Cancer Screening Program in Barretos, Brazil: Experience in 18
      Municipalities of Sao Paulo State.
AB  - OBJECTIVES: The aim of this report is to demonstrate the Barretos Cancer Hospital
      initiative of organizational, laboratorial, and human resources training in the
      implementation of an organized cervical screening program in low-resource
      settings. METHODS: We developed a computational program to report all
      epidemiological, clinical, and laboratorial findings, and to trace all necessary
      information to recruit women for regular screening or for referral for
      complementary exams after liquid-based Pap test analyses. RESULTS: All Pap tests
      were collected in liquid medium and in 2014 more than 160,000 tests were analyzed
      and 2,900 colposcopy examinations were performed. From 2012 to 2015, the
      percentage of exams collected increased from 54.6% in 2012 to 62.4% in 2013,
      68.4% in 2014, and 71% in 2015. Per 1,000 Pap tests, 0.4 cases of invasive cancer
      were diagnosed; for in situ carcinoma, 1.9 cases were identified. More
      importantly, between 2011 and 2015, 89.4% of all carcinomas were detected at
      clinical stage 0 or I (in situ carcinoma), and only 5% at stages III and IV.
      CONCLUSIONS: Since the organized system was implemented, 98% of women have
      attended their recall for colposcopy. So far, we have not reached the target of
      70% of women for this proposal, as recommended by the international standards.

PMID- 29069641
TI  - Diagnosis of Inherited Epidermolysis Bullosa in Resource-Limited Settings:
      Immunohistochemistry Revisited.
AB  - BACKGROUND: Immunofluorescence (IFM) antigen mapping is the most commonly used
      technique to diagnose and differentiate epidermolysis bullosa (EB). In India, IFM
      is limited to few research laboratories and is not readily available, making the
      diagnosis largely clinical and often inaccurate. Ob jective of the Study: To
      examine the diagnostic usefulness of immunohistochemistry (IHC) as compared to
      IFM in resource-limited settings. METHODS: Forty-four consecutive EB patients
      were included in this study. IHC and IFM were performed on 7-um frozen tissue
      sections using standard laboratory protocols with a limited panel of antibodies.
      The kappa coefficient of agreement was calculated with genetic analysis as the
      gold standard. RESULTS: IFM and IHC accurately identified the subtype of EB in
      80.9% (p < 0.001) of the cases, when a clear blister cavity was evident on
      biopsy. The sensitivities and specificities of IHC and IFM for diagnosing EB
      simplex, junctional EB, and dystrophic EB were 100, 100, and 60% and 82.4, 100,
      and 100%, respectively. IHC was equally effective (p < 0.001) in establishing the
      type of EB as IFM. CONCLUSIONS: IHC staining and its interpretation were simple
      and comparable to IFM. IHC had an advantage of showing subtle changes in the
      epidermal architecture that could not be appreciated on IFM and hence can be
      considered useful in resource-limited settings.

PMID- 29069650
TI  - DNAJB1/HSP40 Suppresses Melanoma Differentiation-Associated Gene 5-Mitochondrial
      Antiviral Signaling Protein Function in Conjunction with HSP70.
AB  - Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition
      receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and
      initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer
      along the dsRNA leading to oligomerization, which in turn activates the adaptor
      protein mitochondrial antiviral signaling protein (MAVS) to provide a signal
      platform for the induction of type I interferon (IFN) and proinflammatory
      cytokines. The conformational switch of MDA5 causes antiviral defense, but
      excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases.
      The regulatory mechanisms of MDA5 activation remain largely unknown. By yeast 2
      hybrid, we identified DNAJB1, a member of the HSP40 (heat shock protein 40)
      family, as an MDA5-binding protein. HSP40s usually cowork with HSP70s. We found
      that dsRNA stimulation with physiological conditions upregulated the expression
      levels of DNAJB1 and HSP70; then the proteins were coupled and translocated into
      the stress granules, where MDA5 encounters dsRNA. DNAJB1 disrupted MDA5 multimer
      formation, resulting in the suppression of type I IFN induction. The disruption
      of endogenous DNAJB1 increased MDA5- and MAVS-mediated IFN promoter activation
      and rendered cells virus resistant. HSP70 inhibitor also enhanced the IFN
      inducing function of MDA5 and MAVS. These results suggest that the DNAJB1-HSP70
      complex functions for the natural maintenance of RNA sensing by interacting with
      MDA5/MAVS.

PMID- 29069653
TI  - Intraocular Pressure Spikes within First Postoperative Hours following Standard
      Trabeculectomy: Incidence and Associated Factors.
AB  - PURPOSE: To evaluate the incidence of intraocular pressure (IOP) spikes within
      the first postoperative hours following trabeculectomy (TRAB) and to determine
      possible associated factors. METHODS: An observational study was carried out. We
      enrolled consecutive patients undergoing standard TRAB with mitomycin C. They
      were examined twice within the first few postoperative hours (hours 1-2 and 4-6)
      and 3 times after TRAB (on days 1, 7, and 30). Demographic and ocular data were
      collected. Main outcome measurements were postoperative IOP values at each time
      point and the frequency of IOP spikes, defined as IOP >=25 mm Hg. RESULTS: A
      total of 40 eyes of 40 patients were included (mean age 59.62 +/- 13.37 years).
      Although IOP was significantly reduced to 11.14 +/- 7.99 mm Hg at hours 1-2 (p <
      0.01) and to 11.52 +/- 7.30 mm Hg at hours 4-6 (p < 0.01), IOP spikes were
      documented in 3 patients (7.5%). In the group of patients with IOP spikes, we
      noted that there was a high incidence of black patients and that the surgeries
      had been performed by fellow surgeons. CONCLUSION: Although the majority of the
      cases (92.5% of the patients) did not present IOP spikes, 7.5% of our patients
      presented the event. In selected cases, such as those with advanced disease,
      fixation threat, and of black race, IOP should be monitored during the first few
      postoperative hours for the identification and adequate management of potential
      IOP spikes, preventing undesirable outcomes.

PMID- 29069646
TI  - The Intracranial Aneurysm Gene THSD1 Connects Endosome Dynamics to Nascent Focal
      Adhesion Assembly.
AB  - BACKGROUND/AIMS: We recently discovered that harmful variants in THSD1
      (Thrombospondin type-1 domain-containing protein 1) likely cause intracranial
      aneurysm and subarachnoid hemorrhage in a subset of both familial and sporadic
      patients with supporting evidence from two vertebrate models. The current study
      seeks to elucidate how THSD1 and patient-identified variants function molecularly
      in focal adhesions. METHODS: Co-immunostaining and co-immunoprecipitation were
      performed to define THSD1 subcellular localization and interacting partners.
      Transient expression of patient-identified THSD1 protein variants and siRNA
      mediated loss-of-function THSD1 were used to interrogate gene function in focal
      adhesion and cell attachment to collagen I in comparison to controls. RESULTS:
      THSD1 is a novel nascent adhesion protein that co-localizes with several known
      markers such as FAK, talin, and vinculin, but not with mature adhesion marker
      zyxin. Furthermore, THSD1 forms a multimeric protein complex with
      FAK/talin/vinculin, wherein THSD1 promotes talin binding to FAK but not to
      vinculin, a key step in nascent adhesion assembly. Accordingly, THSD1 promotes
      mature adhesion formation and cell attachment, while its rare variants identified
      in aneurysm patients show compromised ability. Interestingly, THSD1 also
      localizes at different stages of endosomes. Clathrin-mediated but not caveolae
      mediated endocytosis pathway is involved in THSD1 intracellular trafficking,
      which positively regulates THSD1-induced focal adhesion assembly, in contrast to
      the traditional role of endosomes in termination of integrin signals.
      CONCLUSIONS: The data suggest that THSD1 functions at the interface between
      endosome dynamics and nascent focal adhesion assembly that is impaired by THSD1
      rare variants identified from intracranial aneurysm patients.

PMID- 29069647
TI  - alpha-Pinene Inhibits Human Prostate Cancer Growth in a Mouse Xenograft Model.
AB  - BACKGROUND: alpha-Pinene is one of the most widely found terpenoids in nature.
      Substantial evidence shows that alpha-pinene has cancer prevention properties. In
      this study, the PC-3 cell line was used to establish subcutaneous xenograft
      tumors in nude mice. METHODS: Cytotoxicity was measured with the MTT assay, and
      apoptosis and cell cycle analyses were conducted using flow cytometry in vitro.
      The PC-3 cell line was used to establish subcutaneous xenograft tumors in nude
      mice. RESULTS: We found that treatment with alpha-pinene significantly inhibited
      human prostate cancer cell growth and induced apoptosis and cell cycle arrest in
      the cell line-based model. Furthermore, tumor progression was inhibited more in
      mice treated with alpha-pinene than in control mice. We detected less Ki67 and
      proliferation cell nuclear antigen in paraffin sections from xenograft tumor
      specimens taken from alpha-pinene-treated mice than in those from the control
      group. Meanwhile, alpha-pinene treatment induced apoptosis in xenograft tumors as
      determined by the TUNEL assay. CONCLUSIONS: These data strongly suggest that
      alpha-pinene inhibits prostate cancer growth in a xenograft model and may be an
      effective therapeutic agent for prostate cancer treatment.

PMID- 29069656
TI  - Cyclosporine A Induces MicroRNAs Controlling Innate Immunity during Renal
      Bacterial Infection.
AB  - Urinary tract infections (UTIs) mainly due to uropathogenic Escherichia coli
      (UPEC) are one of the most frequent complications in kidney-transplanted
      patients, causing significant morbidity. However, the mechanisms underlying UTI
      in renal grafts remain poorly understood. Here, we analysed the effects of the
      potent immunosuppressive agent cyclosporine A (CsA) on the activation of
      collecting duct cells that represent a preferential site of adhesion and
      translocation for UPEC. CsA induced the inhibition of lipopolysaccharide- induced
      activation of collecting duct cells due to the downregulation of the expression
      of TLR4 via the microRNA Let-7i. Using an experimental model of ascending UTI, we
      showed that the pretreatment of mice with CsA prior to infection induced a marked
      fall in cytokine production by collecting duct cells, neutrophil recruitment, and
      a dramatic rise of bacterial load, but not in infected TLR4-defective mice
      kidneys. This effect was also observed in CsA-treated infected kidneys, where the
      expression of Let-7i was increased. Treatment with a synthetic Let-7i mimic
      reproduced the effects of CsA. Conversely, pretreatment with an anti-Let-7i
      antagonised the effects of CsA and rescued the innate immune response of
      collecting duct cells against UPEC. Thus, the utilisation of an anti-Let-7i
      during kidney transplantation may protect CsA-treated patients from ascending
      bacterial infection.

PMID- 29069643
TI  - 'Repair' Treg Cells in Tissue Injury.
AB  - Studies in mice and humans have elucidated an important role for Tregs in
      promoting tissue repair and restoring tissue integrity. Emerging evidence has
      revealed that Tregs promoted wound healing and repair processes at multiple
      tissue sites, such as the heart, liver, kidney, muscle, lung, bone and central
      nervous system. The localization of repair Tregs in the lung, muscle and liver
      exhibited unique phenotypes and functions. Epidermal growth factor receptor,
      amphiregulin, CD73/CD39 and keratinocyte growth factor are important repair
      factors that are produced or expressed by repair Tregs; these factors coordinate
      with parenchymal cells to limit injury and promote repair. In addition, repair
      Tregs can be modulated by IL-33/ST2, TCR signals and other cytokines in the
      context of injured microenvironment cues. In this review, we provide an overview
      of the emerging knowledge about Treg-mediated repair in damaged tissues and
      organs.

PMID- 29069649
TI  - The Systemic Activation of Programmed Death 1-PD-L1 Axis Protects Systemic Lupus
      Erythematosus Model from Nephritis.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by abnormal
      activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells
      determined B-cells differentiation and cytokines production. The programmed death
      1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and
      its engagement could exhaust T cells. In this study, we investigated the role of
      PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice.
      METHODS: The murine PD-L1-Ig was injected into SLE-prone mice. The proteinuria
      and survival ratio were monitored. The production of anti-dsDNA autoantibodies
      and cytokines in serum were measured by enzyme-linked immunosorbent assay. The
      cytokine-producing T cells (interferon-gamma, IFN-gamma and IL-17alpha) in kidney
      and spleen were detected with flowcytometry. The pathological evaluation of the
      Ig deposition in the glomeruliand was determined with immunofluorescence.
      Lymphocytes in 24-h urine were detected with flowcytometry. RESULTS: The systemic
      administration of PD-L1-Ig activated PD-1-PD-L1 axis of CD4+ T lymphocytes,
      suppressed Th17 formation in many organs, including the spleen and the kidney,
      demolished abnormal production of cytokines (IFN-gamma, IL-17, and IL-10) and
      anti-dsDNA autoantibodies in serum, inhibited immunoglobulin G deposition in the
      glomeruli with the decrease of proteinuria, and activated T cells in urine.
      Accordingly, the systemic conjugation of PD-L1-PD-1 impaired renal autoimmune
      injure and prolonged survival time. CONCLUSION: Our research demonstrated that
      the protective function of systemic activation of PD-1-PD-L1 axis with PD-L1-Ig
      attenuates the nephritis in SLE-prone mice, which facilitates us to understand
      the suppressive function of PD-1-PD-L1 axis in the pathogenesis and progress of
      the lupus nephritis, and to explore a possible effective therapeutic strategy to
      SLE.

PMID- 29069655
TI  - Online Education and e-Consent for GeneScreen, a Preventive Genomic Screening
      Study.
AB  - BACKGROUND: Online study recruitment is increasingly popular, but we know little
      about the decision making that goes into joining studies in this manner. In
      GeneScreen, a genomic screening study that utilized online education and consent,
      we investigated participants' perceived ease when deciding to join and their
      understanding of key study features. METHODS: Individuals were recruited via
      mailings that directed them to a website where they could learn more about
      GeneScreen, consent to participate, and complete a survey. RESULTS: Participants
      found it easy to decide to join GeneScreen and had a good understanding of study
      features. Multiple regression analyses revealed that ease of deciding to join was
      related to confidence in one's genetic self-efficacy, limited concerns about
      genetic screening, trust in and lack of frustration using the website, and the
      ability to spend a limited time on the website. Understanding of study features
      was related to using the Internet more frequently and attaining more information
      about GeneScreen conditions. CONCLUSIONS: The ease of deciding to join a genomic
      screening study and comprehension of its key features should be treated as
      different phenomena in research and practice. There is a need for a more nuanced
      understanding of how individuals respond to web-based consent information.

PMID- 29069637
TI  - Redox active metals and H2O2 mediate the increased efficacy of pharmacological
      ascorbate in combination with gemcitabine or radiation in pre-clinical sarcoma
      models.
AB  - Soft tissue sarcomas are a histologically heterogeneous group of rare mesenchymal
      cancers for which treatment options leading to increased overall survival have
      not improved in over two decades. The current study shows that pharmacological
      ascorbate (systemic high dose vitamin C achieving >= 20mM plasma levels) is a
      potentially efficacious and easily integrable addition to current standard of
      care treatment strategies in preclinical models of fibrosarcoma and liposarcoma
      both in vitro and in vivo. Furthermore, enhanced ascorbate-mediated toxicity and
      DNA damage in these sarcoma models were found to be dependent upon H2O2 and
      intracellular labile iron. Together, these data support the hypothesis that
      pharmacological ascorbate may represent an easily implementable and non-toxic
      addition to conventional sarcoma therapies based on taking advantage of
      fundamental differences in cancer cell oxidative metabolism.

PMID- 29069654
TI  - Expression Profiles of Long Noncoding RNA in UVA-Induced Human Skin Fibroblasts.
AB  - BACKGROUND: Long noncoding RNA (lncRNA) are differentially expressed across
      stages of differentiation and development, but the role of lncRNA in human skin
      photoaging mechanisms remains poorly understood. OBJECTIVE: This study aimed to
      determine lncRNA expression changes in human dermal fibroblasts (HDF) induced by
      repeated UVA irradiation and to explore correlations between lncRNA and skin
      photoaging prognosis. METHODS: In the UVA-HDF group, HDF were subjected to
      repeated UVA irradiation (10 J/cm2 UVA twice daily for 7 days); in the control
      group, HDF received no irradiation. High-throughput sequencing was used to detect
      lncRNA expression profiles. Functional annotation analysis and pathway enrichment
      were preformed via Gene Ontology and KEGG. Predicted lncRNA target genes were
      identified by bioinformatic analysis. RESULTS: In the UVA-HDF group, 1,730 lncRNA
      exhibited over 2-fold expression changes compared with the control group: 1,494
      were upregulated, and 236 downregulated. Predicted lncRNA targets were associated
      with matrix metalloproteinases, cathepsin D, mitogen-activated protein kinase and
      TGF-beta signaling pathways, and collagen fiber metabolism following repeated UVA
      damaging mechanisms. CONCLUSIONS: lncRNA profiles were aberrantly expressed in
      UVA-HDF and might play a key role in skin photoaging. This study provides novel
      insights into the repeated UVA-damaging pathology and potential targets for
      treatment of human skin photoaging.

PMID- 29069662
TI  - AF1q Contributes to Adriamycin-Induced Podocyte Injury by Activating Wnt/beta
      Catenin Signaling.
AB  - BACKGROUND/AIMS: Injury of podocytes plays an important role in decline of
      glomerular filtration and proteinuria. It is well-known that proteinuria is
      associated with numerous chronic kidney diseases (CKD). However, the underlying
      mechanism of podocyte injury remains unclear. METHODS: We used reverse
      transcription-quantitative PCR (RT-qPCR) to compare the expression level of the
      ALL1-fused from the chromosome 1q (AF1q) gene in mice and mouse podocytes (MPC5)
      with or without Adriamycin (ADR) treatment. The effects of AF1q on Wnt/ beta
      catenin signaling were investigated by determining the expressions of desmin,
      snail, WT1, nephrin and E-cadherin using western blotting. RESULTS: We found that
      AF1q expression was elevated in podocytes treated with ADR than untreated cells.
      AF1q overexpression directly led to podocytes injury with increased levels of
      desmin and snail. Luciferase activity of TOPflash reporter was significantly
      increased in cells with AF1q overexpression than wild type cells whereas deletion
      of T-cell-factor-7 (TCF7) eliminated this effect. Immunoprecipitation assay
      evidenced that AF1q interacted with TCF7 and promoted both transcriptional and
      translational expressions of TCF7. Overexpression of AF1q increased protein
      expression of beta-catenin. However, in podocytes with deletion of TCF7, AF1q was
      not able to promote beta-catenin expression. CONCLUSION: Our findings
      demonstrated that aberrant expression of AF1q may activate Wnt/beta-catenin
      signaling and result in podocyte injury.

PMID- 29069651
TI  - Staphylococcus aureus alpha-Toxin Induces Inflammatory Cytokines via Lysosomal
      Acid Sphingomyelinase and Ceramides.
AB  - BACKGROUND/AIMS: Staphylococcus aureus (S. aureus) infections are a major
      clinical problem and range from mild skin and soft-tissue infections to severe
      and even lethal infections such as pneumonia, endocarditis, sepsis,
      osteomyelitis, and toxic shock syndrome. Toxins that are released from S. aureus
      mediate many of these effects. Here, we aimed to identify molecular mechanisms
      how alpha-toxin, a major S. aureus toxin, induces inflammation. METHODS:
      Macrophages were isolated from the bone marrow of wildtype and acid
      sphingomyelinase-deficient mice, stimulated with S. aureus alpha-toxin and
      activation of the acid sphingomyelinase was quantified. The subcellular formation
      of ceramides was determined by confocal microscopy. Release of cathepsins from
      lysosomes, activation of inflammasome proteins and formation of Interleukin-1beta
      (IL-1beta) and Tumor Necrosis Factor-alpha (TNF-alpha) were analyzed by western
      blotting, confocal microscopy and ELISA. RESULTS: We demonstrate that S. aureus
      alpha-toxin activates the acid sphingomyelinase in ex vivo macrophages and
      triggers a release of ceramides. Ceramides induced by S. aureus alpha-toxin
      localize to lysosomes and mediate a release of cathepsin B and D from lysosomes
      into the cytoplasm. Cytosolic cathepsin B forms a complex with Nlrc4. Treatment
      of macrophages with alpha-toxin induces the formation of IL-1beta and TNF-alpha.
      These events are reduced or abrogated, respectively, in cells lacking the acid
      sphingomyelinase and upon treatment of macrophages with amitriptyline, a
      functional inhibitor of acid sphingomyelinase. Pharmacological inhibition of
      cathepsin B prevented activation of the inflammasome measured as release of IL
      1beta, while the formation of TNF-alpha was independent of cathepsin B.
      CONCLUSION: We demonstrate a novel mechanism how bacterial toxins activate the
      inflammasome and mediate the formation and release of cytokines: S. aureus alpha
      toxin triggers an activation of the acid sphingomyelinase and a release of
      ceramides resulting in the release of lysosomal cathepsin B and formation of pro
      inflammatory cytokines.

PMID- 29069652
TI  - Protective Effect of Curcumin Against Oxidative Stress-Induced Injury in Rats
      with Parkinson's Disease Through the Wnt/ beta-Catenin Signaling Pathway.
AB  - BACKGROUND/AIMS: The study aimed to investigate the protective effect of curcumin
      against oxidative stress-induced injury of Parkinson's disease (PD) through the
      Wnt/beta-catenin signaling pathway in rats. METHODS: The successfully established
      PD rat models and normal healthy rats were randomly assigned into the 6
      hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups.
      Immunohistochemistry was used to detect the positive expression of tyrosine
      hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein
      (GFAP). Deutocerebrum primary cells were extracted and classified into the
      control, 6-OHDA, Cur (5, 10, 15 umol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1
      groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell
      viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR
      were used to examine the protein and mRNA expressions of Wnt3a and beta-catenin
      and the c-myc and cyclinD1 mRNA expressions. RESULTS: TH and DAT expressions in
      the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group.
      Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of
      deutocerebrum primary cells by activating the Wnt/beta-catenin signaling pathway.
      Higher Wnt3a and beta-catenin mRNA and protein expressions and c-myc and cyclinD1
      mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated
      mitochondrial membrane potential (?psim) were found in the 10 and 15 umol/L Cur
      groups compared with the 6-OHDA group. However, opposite tendencies were found in
      the Cur + DKK-1 group compared to the 10 umol/L Cur group. CONCLUSION: This study
      suggests that curcumin could protect against oxidative stress-induced injury in
      PD rats via the Wnt/beta-catenin signaling pathway.

PMID- 29069669
TI  - Ultrasound of the Major Salivary Glands is a Reliable Imaging Technique in
      Patients with Clinically Suspected Primary Sjogren's Syndrome.
AB  - OBJECTIVE:  To assess the inter- and intraobserver reliability of ultrasound of
      major salivary glands in patients clinically suspected of having primary
      Sjogren's syndrome (pSS) as well as to assess sources of variation in outcomes of
      ultrasonographic evaluation. METHODS:  80 consecutive outpatients with clinically
      suspected pSS underwent ultrasound evaluation. The following ultrasound variables
      of the parotid and submandibular salivary glands were assessed: echogenicity,
      parenchymal homogeneity, presence of hypoechogenic areas, hyperechogenic
      reflections and clearness of posterior glandular border, according to the scoring
      system of Hocevar et al. (total score range: 0 - 48). Images were scored
      independently by three blinded observers in two sessions. RESULTS:  The
      intraobserver reliability of the total ultrasound score was excellent, with an
      intraclass correlation (ICC) ranging from 0.89 to 0.96. The interobserver
      reliability was good to excellent, with ICCs of 0.84 and 0.76 for the total
      ultrasound score in the two sessions. The kappa value ranged from 0.60 to 0.83
      depending on the applied cut-offs (cut-off score >= 15 and >= 17). Hypoechogenic
      areas and homogeneity of parotid glands showed the highest interobserver
      reliability. The median kappa for echogenicity was low. The total ultrasound
      scores varied more between observers in patients with higher ultrasonographic
      scores (approximately scores >= 20). CONCLUSION:  Ultrasound of major salivary
      glands is a reliable imaging technique for patients with clinically suspected
      pSS. Discrepancies between observers in assessing the severity of ultrasound
      findings may interfere with detecting 'true' changes over time. When monitoring
      the progression of pSS or treatment efficacy, it is advised that a particular
      patient be scored by the same ultrasonographer at every time point.

PMID- 29069670
TI  - ?

PMID- 29069648
TI  - Androgen Receptor Expression and Bicalutamide Antagonize Androgen Receptor
      Inhibit beta-Catenin Transcription Complex in Estrogen Receptor-Negative Breast
      Cancer.
AB  - BACKGROUND/AIMS: Little is known about the potential mechanism of action for
      androgen receptor (AR) targeting treatment in estrogen receptor (ER)-negative
      breast cancer. This study aimed to evaluate AR status and its prognosis in four
      breast cancer subtypes. Bicalutamide has been identified as an AR antagonist and
      used for treating AR+/ER- breast cancer in a phase II trial. Our studies will
      clarify its mechanism in breast cancer treatment. METHODS: A total of 510
      consecutive cases of invasive ductal cancer (IDC) were evaluated in this study.
      The expression of AR was analyzed by immunohistochemistry and compared with
      patient survival, and its implications were evaluated in four subtypes of IDC. We
      examined bicalutamide as an AR antagonist to inhibit proliferation and increased
      apoptosis in AR+/ER- breast cancer cell lines. We explored the tumor suppressive
      functions of bicalutamide in vitro and vivo and its related mechanisms in AR+/ER-
      breast cancer. RESULTS: AR expression was related to that of ER (P<0.001), PR
      (P<0.001), Her2 (P=0.017), Ki-67(P=0.020) and to four subtypes (P<0.001). AR
      retained independent prognostic signifcance (P=0.007, ER- cases; P=0.001, ER+
      cases; P=0.001, total cases). We found that bicalutamide significantly decreased
      viability and increased apoptosis in vitro and vivo. The mechanistic analysis
      revealed that bicalutamide blocked androgen-stimulated oncogenic AR and Wnt/beta
      catenin signaling and inhibited the growth of AR+/ER- breast cancer. CONCLUSION:
      Our studies provide novel insights into bicalutamide as an antagonist of AR
      function in AR+/ER- breast cancer and reveal the mechanistic basis for targeting
      AR as a therapeutic opportunity for patients with AR+/ER- breast cancer.

PMID- 29069661
TI  - Genetics and Insurance in Australia: Concerns around a Self-Regulated Industry.
AB  - BACKGROUND: Regulating the use of genetic information in insurance is an issue of
      ongoing international debate. In Australia, providers of life and other mutually
      rated insurance products can request applicants to disclose all results from any
      genetic test. Insurers can then use this information to adjust premiums and make
      policy decisions. The Australian Financial Services Council (FSC; an industry
      body) developed and maintains the relevant industry standard, which was updated
      in late 2016. Aims/Objective: To review the 2016 FSC Standard in light of
      relevant research and determine the legitimacy of the Australian regulatory
      environment regarding use of genetic information by insurers. RESULTS: We
      identified five concerns arising from the 2016 FSC Standard: (1) use of results
      obtained from research; (2) the requirement for an applicant to disclose whether
      they are "considering" a genetic test; (3) failure to account for genome
      sequencing and other technology developments; (4) limited evidence regarding
      adverse selection; and (5) the inappropriateness of industry self-regulation.
      CONCLUSION: Industry self-regulation of the use of genetic information by life
      insurers, combined with a lack of government oversight, is inappropriate and
      threatens to impede the progress of genomic medicine in Australia. At this
      critical time, Australia requires closer government oversight of the use of
      genetic information in insurance.

PMID- 29069663
TI  - Specific Adoptive Cellular Immunotherapy in Allogeneic Stem Cell Transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a
      treatment option for a diversity of advanced hematopoietic malignancies providing
      hope for long-term responses especially due to immunogenic effects associated
      with the treatment modality. Despite respectable progress in the field, relapses
      and/or opportunistic infections are major reasons for the high treatment-related
      mortality. However, a number of novel immunotherapeutic approaches using defined
      cell populations have been developed to directly target residual malignant cells
      as well as defined infectious diseases. We here provide an overview of current
      adoptive cellular immunotherapies in the context of allo-HSCT and close with an
      outlook on new directions within the field.

PMID- 29069660
TI  - The TiLOOP(r) Male Sling: Did We Forejudge.
AB  - INTRODUCTION: To evaluate the safety and efficacy of the TiLOOP(r) male sling
      (pfm medical, Cologne, Germany) used in the treatment for male stress urinary
      incontinence (SUI). MATERIAL AND METHODS: We retrospectively evaluated a total of
      34 patients with a TiLOOP(r) male sling. Perioperative complication rates were
      assessed and validated questionnaires were prospectively evaluated to assess
      quality of life and satisfaction rate. Outcome and complication rates were
      analysed by using descriptive statistics. Correlation of continence outcome and
      risk factors was performed with the chi-square test. A p value below 0.05 was
      considered statistically significant. RESULTS: The majority of patients (70.6%)
      were diagnosed with mild or moderate male SUI. During surgery, one instance
      (2.9%) of intraoperative urethral injury was observed. There were no immediate
      postoperative complications. The mean follow-up time was 44.6 months. An
      improvement of male SUI was reported by 61.9% of the patients and 38.1% reported
      no change according the Patient Global Impression of Improvement. The mean
      perineal pain score was 0.5 according to the international index of pain.
      CONCLUSIONS: The TiLOOP(r) is a safe treatment option for male SUI in our cohort
      with a low complication rate. However, the functional outcome of the TiLOOP(r)
      was inferior when compared to the outcome of the AdVance(r) male sling.

PMID- 29069668
TI  - Surgical Experience and Learning Points in the Management of Foregut Duplication
      Cysts.
AB  - BACKGROUND:  Foregut duplication cysts (FDC) have unpredictable natural course
      and rarely remain asymptomatic. We present our large cohort of FDC to highlight
      surgical learning points and outcome. MATERIALS AND METHODS:  Review of 41
      children with FDC (April 1997-April 2015) included demographics, clinical
      presentation, preoperative investigations, surgical management, post-operative
      complications, and overall outcome. RESULTS:  Forty-one children (26 girls/15
      boys; male/female [M/F] ratio 1:1.7) had 43 FDC (two cases >1 cyst) consisting of
      antenatally diagnosed 16 (39%), late with symptoms 21 (51.2%), and incidental
      4(9.8%) cases. FDC locations were cervical (3), mediastinal (35), and
      subdiaphragmatic (5). During all cervical FDC resection, recurrent laryngeal
      nerve was required to be dissected off the cyst wall. Thoracoscopic resection was
      feasible in 27 cases, with 4 conversions related to infections and adhesions or
      accidental injury to trachea/esophagus. Complete resection was achieved in all
      cases with no recurrence. There was no mortality and morbidity included,
      chylothorax (1) esophageal injury (1), phrenic nerve injury (1), and tracheal
      injury (2). The minimally invasive surgery and surgery on asymptomatic lesions
      significantly affect the outcome by reducing need for chest drain (p = 0.01) and
      length of hospital stay (p = 0.04). CONCLUSION:  This retrospective study
      confirms the efficacy and safety of thoracoscopic surgery; important learning
      points were association of common wall with trachea in some superior mediastinal
      cysts and association of recurrent laryngeal nerve in cervical FDC.

PMID- 29069672
TI  - ?

PMID- 29069676
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PMID- 29069673
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PMID- 29069671
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PMID- 29069675
TI  - ?

PMID- 29069674
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PMID- 29069677
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PMID- 29069679
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PMID- 29069683
TI  - ?

PMID- 29069681
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PMID- 29069678
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PMID- 29069682
TI  - ?

PMID- 29069689
TI  - [Medical Progress ans Public Health - Results of the Working Group 4 of the Forum
      Future Public Health, Berlin].
AB  - Medical actions that have been shown to be beneficial in individual studies may
      be associated with a negative benefit-harm balance at the population level due to
      oversupply or undersupply. Therefore, structured dialogues among basic
      researchers, clinicians and public health researchers are needed to generate
      relevant public health questions in relation to medical actions and to undertake
      research projects that answer these questions. For this purpose, more structured
      PhD programs in public health are required. Implementation barriers for evidence
      based medical actions in the population need to be identified and tailored
      interventions to reduce these barriers need to be developed and evaluated.

PMID- 29069686
TI  - ?

PMID- 29069690
TI  - [Health Promotion and Disease Prevention - Results of the Working Group 6 of the
      Forum Future Public Health, Berlin 2016].
AB  - The increase in so-called lifestyle-related diseases emphasizes that focusing
      health care systems on the diseased population is insufficient to meet the
      challenges of population health. Instead, a proactive reorientation of health
      care structures towards more disease prevention, health promotion, and health
      protection is necessary. In addition to national institutions, municipal and non
      governmental structures (public health services, health conferences etc.) play a
      central role in the implementation of such structural changes, as they are the
      societal organizations in direct contact with citizens.

PMID- 29069680
TI  - ?

PMID- 29069691
TI  - [Results of Evaluation of Academic Initial Vocational Training in Therapeutic
      Professions].
AB  - Aim With focus on 2 points, we summarize the results of the evaluations of up to
      13 model degree courses in therapeutic health professions. The aim was to
      investigate the structural conception of the degree courses and the competencies
      of the students. Methods We use content analysis to find out common structures in
      officially binding documents, such as accreditation documents, evaluation
      documents and study plans. To analyse competencies, we use a mixed method design:
      A validated assessment tool enables students to estimate their own competencies
      (self-assessment) (N=286) and qualitative interviews which focus on expert
      therapists in the practice field (peer-assessment) (N=29). Results Regarding the
      structural conception, the degree courses generate solutions that are strongly
      marked by application of the present vocational law that is in many places not
      compatible with academic standards. As far as competencies are concerned,
      academic initial vocational training enables students to work scientifically.
      With this, the degree courses successfully develop competencies in students that
      are necessary to meet the current health care requirements. Consequences The
      results support the recommendation to reform the vocational law regulations and
      to implement the model degree courses into regular legal structures.

PMID- 29069684
TI  - ?

PMID- 29069685
TI  - ?

PMID- 29069688
TI  - [Global Public Health - Results of the Working Group 3 of the Forum Future Public
      Health, Berlin 2016].
AB  - In the age of globalization, few health issues remain "local". For example,
      neither infectious diseases nor climate change stop at national borders, and
      hence cannot be controlled only within the nation state. The same applies to
      smoking and nutritional behaviors that affect health and are influenced by
      multinational companies and transnational policies. Therefore, public health
      needs to develop strategies and interventions that are not restricted to the
      nation state alone. This also applies to public health in Germany that needs a
      stronger global health perspective.

PMID- 29069687
TI  - ?

PMID- 29069697
TI  - [How Representative are Participants of a Parent Survey in the Context of School
      Entrance Examination].
AB  - AIM: In an evaluation study of preventive programmes, the recruitment success of
      families in difficult socio-economic circumstances was examined during the school
      entrance examination (SEE). METHOD: Using a 3-stage recruitment procedure,
      parents were motivated to participate in the survey. The response rate was
      calculated for the entire cohort and separately for the single recruitment
      stages. Non-participants and participants were compared on 4 indicators of
      difficult socio-economic circumstances. RESULTS:  52% of the parents participated
      in the study. The response rate reached 21% for the recruitment stage
      'questionnaire with invitation to the SEE', 28% for stage 'personal delivery at
      the health department' and 4% for stage 'stamped addressed envelope'. Families
      with low education were more often non-participants (multivariate Odds Ratio (OR)
      2.2; 95%-confidence interval (CI) 1.3-3.6). Marginal differences in study
      participation were present for unemployed families (OR 1.4; CI 0.6-3.2), single
      parents (OR 1.0; CI 0.6-1.8) and families with immigration background (OR 1.2; CI
      0.7-1.5). CONCLUSION: The response rate was adequate. Personal delivery achieved
      the highest response rate compared to the other stages. A parent survey at the
      SEE is a promising approach to access families in difficult socio-economic
      circumstances. Nevertheless, families with low education are still
      underrepresented.

PMID- 29069692
TI  - [Intragenerational Mobility and Subjective Health: Findings of the Socio-Economic
      Panel (GSOEP) 1992-2012].
AB  - Aim of the study International research suggests that mobility plays an important
      role in determining health in later life. The aim of this study was to analyze
      the relationship between intragenerational mobility and subjective health on the
      basis of data from Germany, taking different periods from 1992 to 2012 into
      account. Data and Methods Data is derived from the Socio-economic Panel (GSOEP),
      taking three time periods into account (1992-1995, 2000-2003 and 2008-2012).
      Intragenerational mobility was measured by comparing first occupational position
      and current job. Logistic regressions were used in order to analyze the
      relationship between health and mobility. Results Men and women who were
      downwardly mobile in unemployment or stable low reported the worst health. Up-
      and downwardly mobile people were located between the stable-up and stable-low
      groups. The relationship was not affected by origin (East/West Germany). Yet,
      upward mobility was more common in West Germany and downward mobility was more
      frequent in East Germany. In general, men and women showed similar patterns. The
      relationship between intragenerational mobility and health remained stable over
      time. Conclusion Occupational development showed a strong relationship with
      health in later life. Especially downward mobility into unemployment or staying
      in lower positions had strong influence on health. Socio-political measures
      should be taken to prevent a further divergence of health opportunities.

PMID- 29069698
TI  - [Motivation of Men to Participate in Physical Activity Programs for Health
      Promotion].
AB  - Study aim The rate of men participating in health promotion programs is lower
      than that of women. The reasons and barriers for the different motivation of men
      as well as wishes and perception for prevention are not yet sufficiently
      analyzed. This quantitative survey examines motives and barriers of men for
      participation in primary prevention. Thus, the sample was subdivided into 2
      groups, namely motivated vs. non-motivated regarding being active for health
      promotion. Differences between the 2 groups concerning current health status,
      health beliefs and health behavior were analyzed to plan more suitable programs
      in the future. Methods A sample of N=243 men (motivated n=147, non-motivated
      n=96) participated in the standardized online-survey. The quantitative data
      analysis integrated the BMZI, KKG, SF-12, TICS and the MGV-39. The examination of
      the differences between the sub-groups was done with Chi2-Tests and analysis of
      variance (one-way ANOVA) with IBM SPSS 22 (Armonk, NY: IBM Corp). Results The
      group of motivated men reported worse health status, especially in psychological
      well being compared to the non-motivated group (SF-12: F=6.3, p=0.013,
      eta2=0.025). Both groups named refusal to use harmful substances (e.g. drugs,
      alcohol), good nutrition and active life-style as important factors for health.
      Non-motivated men showed a higher score for the fatalistic externality of health
      (KKG: F=7.609, p=0.006, eta2=0.031) and rated health promotion as paternalism
      (Chi2=17.693, p<=0.001, C=0.261). Conclusion The men of this study who were
      motivated to join health promotion programs had a worse health status that might
      explain their compliance. For the non-motivated men, there was a discrepancy
      between their own beliefs in health behavior and their real daily activities
      (e.g. physical activity). In order to reach this target group of men before their
      health status worsens, prevention programs should integrate incentive systems
      that integrate features for overcoming dysfunctional daily behavior.

PMID- 29069701
TI  - Endoscopic full-thickness resection of fistula tract with suture closure.

PMID- 29069693
TI  - [The Image of Doctors in Europe: A Comparison of Countries].
AB  - STUDY OBJECTIVE: Patients expect a lot from doctors. They expect doctors to be
      trustworthy and competent, to discuss all treatment options with them, to inform
      them about mistakes made during the treatment and to put their interests before
      their own interests. This paper examines how the population of Europe assesses
      doctors in this respect and whether there are countries where the assessments are
      similar. METHODS: In the "International Social Survey Programme - ISSP" the
      population in 32 countries was asked to assess the doctors in their respective
      countries. For this paper, data of 27,772 respondents from 18 European countries
      were analysed. The respondents were asked to rate 5 statements about doctors on a
      5-point scale, with 1 indicating a positive assessment and 5 indicating a
      negative assessment. For each country, the mean values for the statements were
      calculated and grouped using cluster analysis to identify countries with similar
      assessments. RESULTS: "Doctors can be trusted" is the statement with the highest
      approval across all countries, with means ranging from 2.0 in Denmark to 2.7 in
      Russia. In most countries, the means of the following statements were close to
      each other: "Doctors discuss all treatment options with their patients", "The
      medical skills of doctors are as good as they should be", and "Doctors do not
      care more about their earnings than about their patients." In almost all
      countries, respondents were particularly skeptical about the statement "Doctors
      would tell their patients if they had made a mistake during treatment". Four
      clusters were identified, but there was no cluster that rated among the best for
      all five statements. With regard to trust, the discussion of treatment options
      and the pursuit of self-serving interests, doctors in Germany were not rated
      particularly well or particularly badly. In Germany, the population was more
      likely to think that doctors would not inform their patients about mistakes
      during the treatment. CONCLUSIONS: Trust in doctors seems to reflect the general
      level of trust in a country. The question arises why trust in doctors is high
      across countries if the respondents are much more skeptical regarding the other
      statements.

PMID- 29069694
TI  - [Glove Disinfection: Knowledge, Experiences and Attitudes of Hygiene Team Members
      and Company Physicians].
AB  - BACKGROUND: Chemical-resistant single-use gloves allow the practice of glove
      disinfection. However, there are different recommendations for their use.
      MATERIAL AND METHODS: We conducted a standardized survey during an infection
      control meeting and an occupational health symposium in order to gain data on
      knowledge, experiences and attitudes of hygiene team members and occupational
      health physicians in hospitals with regard to glove disinfection by group
      comparison. RESULTS: 558 out of 1000 questionnaires were returned, among them 246
      (44.1%) from infection control practitioners, 63 (11.3%) from link-nurses, 39
      (7.0%) from hospital epidemiologists, 97 (17.4%) from link-physicians, and 46
      (8.2%) from occupational health physicians. The remaining 67 participants worked
      in multiple other areas. 75% of infection control professionals, 35% of
      occupational health physicians and 25% of nurses and physicians were contacted
      regarding glove disinfection within the last 12 months. In many institutions,
      glove disinfection is not allowed; 67% of respondents voted against it. Large
      deficits regarding disposable gloves were reported. CONCLUSION: The topic of
      glove disinfection is primarily an issue for the infection control team. However,
      a close cooperation with occupational health physicians is warranted but is not
      practiced. There is relevant uncertainty regarding the presupposition of
      disinfectable gloves and the practical utilization of glove disinfection.

PMID- 29069703
TI  - "Step-clipping" method: a technique for detecting previously bleeding
      diverticula.

PMID- 29069707
TI  - [Homer's Blindness].

PMID- 29069699
TI  - [Global Health Comprises More than Health Security: Discussion].
AB  - Global health is increasingly present on the international policy agenda and in
      transnational fora such as the G7 and G20 summits. This trend is as overdue as it
      is desirable, but the scope and content of the discussion remain rather limited.
      For safeguarding and improving people's health all over the world, global public
      health requires coordinated and coherent action. Epidemic preparedness is
      certainly necessary but refers only to a small segment of global health and will
      remain insufficient as long as the social and health-system-related causes
      persist. "One Health" is an important strategy for fighting antimicrobial
      resistance but without overcoming crucial economic determinants, it will be
      impossible to solve the problem. Health systems strengthening, the third major
      field of global health, requires a sound mix of adequate financing,
      infrastructure, human resources and societal factors for expanding access to
      health for all. All proposed and desired improvements in global health need
      complex crosscutting approaches for being effective and sustainable; however, the
      steps taken by political decision-makers are rather small and do not address
      essential causes. Global public health means more than tinkering with the
      symptoms.

PMID- 29069696
TI  - [Benefits of a Medication List from a Citizen's Perspective -A Qualitative
      Survey].
AB  - BACKGROUND: Since October 2016, German patients are entitled to get a medication
      list if using at least 3 drugs. The patient's individual attitude to a medication
      list is supposed to be relevant for its use und acceptance. STUDY AIM: Because
      there is little known about those attitudes, this study examined which potential
      benefits patients see in possessing a medication list, and why certain patients
      might not use it. METHOD: In a qualitative survey, 375 citizens of the Rhein
      Neckar region were interviewed by using a semi-standardized guide. A content
      analysis of the interviews was done. RESULTS: Most citizens described medication
      lists as having private and economic benefits such as for health care or safe
      drug use. But often, they combine potential benefits with requirements such as
      age, number of prescribed drugs, or health status. Unsatisfied individual needs,
      excessive demands or an attitude of rejection are possible reasons for non-use.
      CONCLUSION: For successful implementation of the medication list, the individual
      attitude of patients should be assessed to be able to provide tailored
      information and assistance. The views of citizens about a medication list agree
      with the aims of the so-called German E-Health Act, but differ particularly with
      regard to named requirements and prioritisation.

PMID- 29069695
TI  - [Oral Health in Children and Adolescents with Mental Disability and Psycho
      Emotional Disorders from Lower Saxony and Thuringia].
AB  - Aim This study aimed to compare the oral health status of 6-16 year old pupils
      with mental disability (MD) and psycho-emotional disorders (PED) from Lower
      Saxony (LS) and Thuringia (TH). Methods Oral examination was provided for 571
      pupils with MD from TH, 118 students with MD and 80 students with PED from LS.
      Caries experience, odontogenic infections, fissure sealants and periodontal
      health were recorded. Data were statistically analysed by linear and binary
      logistic regression after adjusting for age. Results Students with PED revealed
      highest caries prevalence and experience in both dentitions with highest
      prevalence of odontogenic infections in the primary dentition. In 6-11 year old
      pupils with MD, there were only minor differences in odontogenic infections
      between TH and LS. Pupils with PED aged 6-11 years had a more that two-fold
      higher risk to develop dental caries and odontogenic infections than peers with
      MD. Care index was higher in pupils with PED compared to those with MD in both
      dentitions. Pupils with MD from TH were less affected with dental caries and
      received better care than those from LS. Compared to peers without mental
      disabilities or disorders, pupils with MD or PED were more affected with dental
      caries in both dentitions. They revealed a lower care index and less fissure
      sealants. Conclusion Pupils with MD or PED reveal unsatisfactory oral health
      status constituting a group with particular high caries risk, while those with
      PED are most affected by caries and odontogenic infections. The care index is
      insufficient especially in pupils with MD compared to those with PED or peers
      without disabilities and indicates disparity in oral health for this vulnerable
      group.

PMID- 29069702
TI  - A retroperitoneal mass confirmed as a pancreatic adenosquamous carcinoma by
      endoscopic ultrasound-guided fine-needle aspiration.

PMID- 29069708
TI  - [The 100 Most Often Articles on Glaucoma Research: a Bibliometric Analysis].
AB  - Background Bibliometric science employs statistical and quantitative analyses to
      analyse the scholarly impact and characteristics of publications within a
      research field. The present study was initiated to analyse and quantify the 100
      most often cited papers in glaucoma research. Materials and Methods The databases
      of the Institute for Scientific Information were utilised for the identification
      of articles published from 1900 to December 2016. All glaucoma articles were
      identified that had been published in 109 relevant journals and which had been
      cited at least 200 times. The top 100 articles were selected for further analysis
      of authorship, source journal, number of citations, citation rate, geographic
      origin, article type, and level of evidence. Results The publication dates of the
      100 most often cited articles ranged from 1966 to 2011, with the greatest number
      of articles published in the 1990s. Citations per article ranged from 258 to
      1908. All articles were published in 18 of the 109 journals. The leading
      countries of origin were the U. S. A., followed by the U. K. The study focussed
      on two main clinical articles (diagnostics; epidemiology) and basic research
      articles. The number of citations per article was greatest for articles published
      in the 2000s. Most articles provided level III evidence, followed by levels I and
      II. Conclusion The majority of the most cited articles were published in three of
      the top-ranked journals. Most clinical articles dealt with epidemiology and
      diagnostics. Individuals who authored multiple articles in the list often
      focussed on one of these two areas. Most studies were conducted in the U. S. A.
      and presented level III clinical outcomes. This indicates that even studies with
      small case series or cohort studies can attract attention.

PMID- 29069706
TI  - [Excellence in Ophthalmology: Nobel Prize Nominees 1901 - 1960].

PMID- 29069709
TI  - Ptosis Surgery in Patients with Myasthenia Gravis: A Useful Adjunct to Medical
      Therapy.
AB  - INTRODUCTION: Medical management can have limitations in improving ptosis in
      patients with myasthenia gravis (MG). We present our experience of ptosis surgery
      in MG. MATERIALS AND METHODS: Clinical records of all patients with MG undergoing
      ptosis surgery from September 2007 to November 2013 in a single center were
      retrospectively reviewed. Change in upper marginal reflex distance (uMRD) was the
      main outcome measure. RESULTS: Sixteen external levator advancement (ELA)
      procedures were performed on 11 MG patients. Fourteen of 16 procedures had pre-
      and postoperative uMRD documented. Thirteen of 14 procedures had improved lid
      height; mean increase in uMRD was 2.4 mm (P=0.0005651). Two patients required
      secondary lid elevation. Postoperative complications included more noticeable
      diplopia (n=1) and exposure keratopathy (n=1). CONCLUSION: Ptosis surgery is a
      useful adjunct to medical therapy to improve lid height in MG patients with
      ptosis. Risks of diplopia and exposure keratopathy should be discussed with the
      patient pre-operatively.

PMID- 29069704
TI  - Saline with methylene blue-assisted endoscopic ultrasound-guided
      gastrojejunostomy using a double-flared fully covered metal stent.

PMID- 29069705
TI  - [The Impact of Multiple Intravitreal Anti-VEGF Injections on Intraocular
      Pressure].
AB  - BACKGROUND: To evaluate the possible effects of multiple intravitreal anti
      vascular endothelial growth factor (VEGF) injections on intraocular pressure
      (IOP). METHODS: This study included 50 eyes of 50 patients who underwent multiple
      (>= 10 injections) intravitreal anti-VEGF injections in one eye with age-related
      macular degeneration, diabetic macular edema or retinal vein occlusion. IOP was
      recorded after every injection on the first postoperative day. IOP > 21 mmHg was
      regarded as abnormal. For statistical analysis, the IOP was correlated with the
      number of injections. RESULTS: A total of 669 IOP-measurements (mean 13.4
      treatment/eye) were analyzed. No IOP-elevation was recorded in 43 eyes (86%).
      Transient elevated IOP > 21 mmHg was measured after 19 intravitreal injections
      (2.8%, one patients with 8 IOP elevations). In general, there was no increasing
      risk of IOP elevation with time, no case of sustained IOP elevation and no
      additional long term glaucoma treatment necessary. Eyes with pre-existing
      glaucoma were significantly more affected from transient IOP-elevation than non
      glaucoma eyes (5.5 vs. 2.2%). CONCLUSIONS: Multiple anti-VEGF injections are not
      associated with an increased risk of sustained IOP-elevation. On the other hand,
      individual risk factors exist and predispose to IOP-elevation (e.g., pre-existing
      glaucoma).

PMID- 29069710
TI  - Success Rates of Endoscopic-Assisted Probing Compared to Conventional Probing in
      Children 48 Months or Older.
AB  - BACKGROUND: To evaluate the success rates of endoscopic-assisted probing compared
      to conventional probing in children 48 months or older. METHODS: This
      retrospective study included children 48 months and older with CNLDO who
      underwent endoscopic-assisted probing or conventional probing between January
      2011 to August 2015 at a tertiary eye care hospital in central Saudi Arabia.
      Probing was considered successful when signals of tearing or discharge
      disappeared and fluorescein dye disappearance test (FDDT) was normal. Demographic
      data, clinical features, intraoperative and postoperative variables were
      correlated to the success rate. RESULTS: One hundred and twelve children with
      CNLDO undergoing endoscopic-assisted (37 patients) or conventional (75 patients)
      probing were included. The success rates of endoscopic-assisted and conventional
      probing were 94.6% [95% confidence interval (CI): 89.5-99.7] and 58.7% [95% (CI):
      47.6-69.8], respectively. The success rate was higher with endoscopic probing,
      especially in older children. CONCLUSIONS: Endoscopic-assisted probing can
      achieve better outcomes to treat CNLDO, even in older children. The significantly
      higher success rates with endoscopic probing are likely due to the ability to
      observe and treat associated problems.

PMID- 29069712
TI  - Optimization and evaluation of lyophilized fenofibrate nanoparticles with
      enhanced oral bioavailability and efficacy.
AB  - The objective of this study was to enhance physiochemical properties as well as
      oral bioavailability of the poorly water soluble drug fenofibrate (FB), through
      preparation of amorphous solid dispersions (ASDs). ASDs were prepared via freeze
      drying using polyvinylpyrrolidone (PVP) K30 and poloxamer 188 as hydrophilic
      carriers. Formulations were optimized by 32 full factorial design (FFD) with PVP
      K30 level (X1) and poloxamer 188 level (X2) as independent variables and particle
      size (Y1), zeta potential (Y2), drug content (Y3) and dissolution rate (T90,
      [Y4]) as dependent variables. Optimized FB nanoparticles were physicochemically
      evaluated and formulated into lyophilized sublingual tablets. Pharmacokinetic,
      pharmacodynamics and histological finding of optimized formulation were performed
      on rabbits. Y1 and Y4 were significantly affected by independent variables while
      Y2 and Y3 were not affected. Physicochemical characterization showed the drug was
      in amorphous state, nanometer range and pharmacophore of FB was preserved.
      Administration of optimized FB tablets to rabbits with fatty liver led to
      significant reduction (p < 0.001) in serum lipids. Moreover, histological
      analysis of liver specimens confirmed the improved efficacy in animals with fatty
      liver. In this study, we confirmed that ASDs of FB had beneficial effects on
      managing fatty liver and serum lipids level in hyperlipidemic rabbits.

PMID- 29069700
TI  - Evaluation of Cortisol Production in Aldosterone-Producing Adenoma.
AB  - Aldosterone-producing adenoma (APA) is sometimes accompanied with subclinical
      hypercortisolism. We investigated the ability of cortisol production in APA, both
      clinically and pathologically. A retrospective cohort study was conducted at
      Yokohama Rosai Hospital from 2009 to 2016. Thirty patients with APA and serum
      cortisol levels during the 1 mg dexamethasone suppression test (F-DST)<3.0 MUg/dl
      were included. We evaluated the 1) difference between pre-adrenalectomy F-DST
      (pre-F-DST) and post-adrenalectomy F-DST (DeltaF-DST), 2) correlation between ?F
      DST and pre-F-DST, tumour size determined by CT, and type of adrenalectomy (total
      or partial), and 3) relationship between the ratio of F-DST divided by tumour
      size (DeltaF-DST/pre-F-DST/mm) and immunoreactivity of CYP17A1, CYP11B1, and
      CYP11B2. The median [interquartile range] age was 48 [38-58] years. We found a
      significant decrease in F-DST after adrenalectomy [before: 1.4 (1.1-1.8); after:
      0.9 (0.6-1.2); p<0.001]. Additionally, a significant correlation was found for
      DeltaF-DST and both pre-F-DST (Spearman, rho=-0.68, p<0.001) and tumour size
      (rho=-0.51, p 0.005). No significant difference was found in DeltaF-DST between
      total and partial adrenalectomy. CYP17A1 and CYP11B1 were positive in 21 (100%)
      and 17 (81%) adenomas, respectively. CYP17A1 immunoreactivity in the tumour was
      significantly related with DeltaF-DST/pre-F-DST/mm (p 0.049). F-DST significantly
      decreased after adrenalectomy, and most of the adenomas were
      immunohistochemically positive for CYP17A1 and CYP11B1 as well as CYP11B2. We
      should consider the possibility of autonomous cortisol production as well as
      hyperaldosteronism in the evaluation and treatment of APA patients.

PMID- 29069713
TI  - Selective DNA methylation in cancers controls collateral damage induced by large
      structural variations.
AB  - Chromosomal instability is a hallmark of human cancers, and is characterized by
      large structural variations in the genome. Such large structural variations are
      expected to create intrinsic collateral stress due to gene dosage changes in many
      genes that are co-deleted or co-amplified in large chromosomal segments (onco
      passenger genes). We show that the tumor-toxic effects of gene dosage changes of
      onco-passenger genes are compensated by the uncoupling of their copy number
      variations from their expression by means of selective DNA methylation. For
      example, collateral co-amplification of genes in tumor suppressor pathways, such
      as the TGF-beta and inflammatory signaling pathways, are compensated by DNA
      hypermethylation to suppress their overexpression, while collateral deletion of
      pro-oncogenic genes are compensated by DNA hypomethylation to promote their
      expression from the single remaining allele. Our work reveals an important
      tumorigenic mechanism of regulation of toxic gene copy number imbalance in tumor
      cells arising from chromosomal instability, and suggests that targeting the DNA
      methylation machinery may prevent compensatory regulation of onco-passenger gene
      expression in chromosomally unstable cancers, and re-activate dormant tumor
      suppressor pathways for effective therapy.

PMID- 29069711
TI  - Gambogic acid-loaded PEG-PCL nanoparticles act as an effective antitumor agent
      against gastric cancer.
AB  - Poor water solubility and side effects hampered the clinical application of
      gambogic acid (GA) in cancer therapy. Accordingly, GA-loaded polyethylene glycol
      poly(E-caprolactone) (PEG-PCL) nanoparticles (GA-NPs) were developed and
      administered peritumorally to evaluate their antitumor activity. The particle
      size, polydispersity index, encapsulation efficiency and loading capacity of GA
      NPs were 143.78 +/- 0.054 nm, 0.179 +/- 0.004, 81.3 +/- 2.5% and 14.8 +/- 0.6%,
      respectively. In addition, GA-NPs showed excellent stability, good
      biocompatibility and sustained release profile. Endocytosis studies in vitro
      demonstrated that the GA-NPs were effectively taken up by tumor cells in a time
      dependent manner. In vivo real-time imaging showed that the nanoparticles
      effectively accumulated within the tumor tissue after peritumoral administration.
      The cytotoxicity study revealed that the GA-NPs effectively inhibited the
      proliferation of gastric cancer cells. In vivo antitumor therapy with peritumoral
      injection of GA-NPs exhibited superior antitumor activity compared with free GA.
      Moreover, no toxicity was detected in any treatment group. Histological studies
      confirmed a lower cell density and a higher number of apoptotic cells in the GA
      NPs group compared with the free GA group. Furthermore, the expression level of
      the cysteine proteases 3 precursor (pro-caspase3), a crucial component of
      cellular apoptotic pathways, was efficiently reduced in mice treated with GA-NPs.
      In conclusion, the GA-NPs system provided an efficient drug delivery platform for
      chemotherapy.

PMID- 29069715
TI  - Inhibition of extracellular matrix mediated TGF-beta signalling suppresses
      endometrial cancer metastasis.
AB  - Although aggressive invasion and distant metastases are an important cause of
      morbidity and mortality in patients with endometrial cancer (EC), the requisite
      events determining this propensity are currently unknown. Using organotypic three
      dimensional culture of endometrial cancer cell lines, we demonstrated anti
      correlated TGF-beta signalling gene expression patterns that arise among
      extracellular matrix (ECM)-attached cells. TGF-beta pathway seemed to be active
      in EC cells forming non-glandular colonies in 3D-matrix but weaker in glandular
      colonies. Functionally we found that out of several ECM proteins, fibronectin
      relatively promotes Smad phosphorylation suggesting a potential role in
      regulating TGF-beta signalling in non-glandular colonies. Importantly, alteration
      of TGF-beta pathway induced EMT and MET in both type of colonies through slug
      protein. The results exemplify a crucial role of TGF-beta pathway during EC
      metastasis in human patients and inhibition of the pathway in a murine model
      impaired tumour cell invasion and metastasis depicting an attractive target for
      therapeutic intervention of malignant tumour progression. These findings provide
      key insights into the role of ECM-derived TGF-beta signalling to promote
      endometrial cancer metastasis and offer an avenue for therapeutic targeting of
      microenvironment derived signals along with tumour cells.

PMID- 29069718
TI  - Androgen receptor amplification is concordant between circulating tumor cells and
      biopsies from men undergoing treatment for metastatic castration resistant
      prostate cancer.
AB  - Increased AR activity has been shown to be preserved in spatially distinct
      metastatic tumors from the same patient suggesting the requirement for lineage
      specific dependencies for metastatic castration resistant prostate cancer
      (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC
      increase AR activity. To determine whether AR amplification in circulating tumor
      cells (CTC) could complement metastatic tissue biopsies in men undergoing
      treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and
      subsequently analyzed AR amplification status in CTCs and matched biopsy tissue
      from the same patient by fluorescence in situ hybridization (FISH). AR gene
      status in CTCs showed strong concordance with AR gene status in matched tissue
      samples in 24 of 25 patients (Correlation: 96%; Kappa: 0.83; Sensitivity: 100%,
      Specificity: 83%). Our work demonstrates that AR amplification is conserved
      between CTCs and biopsies and that CTCs can serve as non-invasive surrogate to
      document AR amplification in mCRPC.

PMID- 29069714
TI  - Racial differences in prostate inflammation: results from the REDUCE study.
AB  - Prostate cancer (PC) risk differs between races, and we previously showed
      prostate inflammation in benign prostate tissue was linked with a lower future PC
      risk. However, whether prostate tissue inflammation varies by race is unknown. We
      analyzed baseline acute and chronic prostate inflammation by race in REDUCE, a 4
      year, multicenter, placebo-controlled study where all men had a negative prostate
      biopsy prior to enrollment. We included 7,982 men with standardized central
      pathology review to determine the presence or absence of chronic or acute
      inflammation in baseline prostate biopsy tissue. Logistic regression was used to
      compare prostate inflammation by race, adjusting for confounders. Of 7,982 men,
      7,271 were white (91.1%), 180 (2.3%) black, 131 (1.6%) Asian, 319 (4.0%) Hispanic
      and 81 (1%) unknown. A total of 78% had chronic and 15% had acute inflammation.
      On multivariable analysis relative to white men, black men were less likely (OR =
      0.65, 95%CI: 0.41-1.03, p = 0.07) and Asian men more likely to have acute
      inflammation (OR = 1.74, 95%CI: 1.14-2.65, p = 0.001). Hispanic men had similar
      levels of acute inflammation as white men. Chronic inflammation did not
      significantly differ across races. We identified racial differences in acute
      inflammation, particularly in Asian men, in benign prostate tissue that inversely
      mirrored population-level data on PC race disparity. As we showed in REDUCE that
      acute inflammation is linked with lower future PC risk, if validated in future
      studies, these data suggest racial differences in prostatic acute inflammation
      may contribute in part to race differences in PC risk, especially among Asian
      men.

PMID- 29069716
TI  - miR-338-3p inhibits epithelial-mesenchymal transition and metastasis in
      hepatocellular carcinoma cells.
AB  - Down-regulation of the miRNA miR-338-3p correlates with the invasive ability of
      hepatocellular carcinoma (HCC) cells. However, it is currently unclear whether
      down-regulation of miR-338-3p induces epithelial-mesenchymal transition (EMT),
      which may be the underlying mechanism governing HCC invasion. Here, we
      demonstrate that restoration of miR-338-3p expression via transfection of a miR
      338-3p mimic reversed EMT and inhibited the motility and invasiveness of HCC
      cells. Conversely, silencing of endogenous miR-338-3p expression with a miR-338
      3p-specific inhibitor induced EMT and enhanced HCC cell motility. Additionally,
      Snail1 (an upstream regulatory protein of EMT) and Gli1 (a key transcription
      factor in the sonic hedgehog (SHH) signaling pathway) expression was up-regulated
      in cells treated with the miR-338-3p inhibitor and down-regulated by the miR-338
      3p mimic. Further analyses demonstrated that miR-338-3p inhibitor-induced EMT in
      HCC cells was blocked by treatment with a small interfering RNA (siRNA) targeting
      Snail1, that the SHH signaling pathway was required for both miR-338-3p inhibitor
      induced EMT and up-regulation of Snail1, and that miR-338-3p targeted a sequence
      within the 3'-untranslated region of N-cadherin mRNA. Notably, miR-338-3p
      expression was significantly down-regulated in HCC samples from patients with
      metastases and was associated with poor metastasis-free survival rates. Lastly,
      correlations between the expression levels of miR-338-3p and E-cadherin,
      Smoothened (SMO), Gli1, Snail1, N-cadherin, and vimentin were confirmed in HCC
      xenograft tumors and HCC patient specimens. Our findings suggest that miR-338-3p
      suppresses EMT and metastasis via both inhibition of the SHH/Gli1 pathway and
      direct binding of N-cadherin. miR-338-3p is a potential therapeutic target for
      metastatic HCC.

PMID- 29069724
TI  - Association of serum Ninjurin2 levels with neurologic damage and postherpetic
      neuralgia occurrence: an observational cohort study in chinese herpeszoster
      patients.
AB  - OBJECTIVES: Postherpetic neuralgia(PHN) is the most common complication of
      herpeszoster (HZ) infection. The study aimed to explore whether serum Ninjurin2
      (for nerve injury-induced protein 2, NINJ2), a novel neurologic damage related
      protein, is associated with nerve injury and the occurrence of PHN. RESULTS:
      Seventy-four of the eighty patients completed the study. On the 7th day of AHN,
      the patients had significantly higher values of NINJ2, cold-sense dispersion
      (DeltaCS), warm-sense dispersion (DeltaWS), cold-pain dispersion (DeltaCP), heat
      pain dispersion (DeltaHP) and NRS score compared to controls. Six months after
      herpes, thirty four patients developed PHN. The values of serum NINJ2, DeltaCS,
      DeltaWS, DeltaCP and DeltaHP in PHN patients remained higher than in the controls
      and the patients who did not develop PHN. The PHN patients had significantly
      lower values of serumNINJ2 than patients who did not develop PHN in the period of
      AHN. With partial correlations and multivariable logistic regressions, serum
      NINJ2 level was strongly predictive of PHN. MATERIALS AND METHODS: Eighty
      individuals with acute herpetic neuralgia (AHN) and 60 controls were recruited.
      The following nerve injury testing was performed on all of the patients
      including: the numerical rating scale (NRS) test, quantitative sensory testing
      (QST), and the investigation of serum NINJ2 levels on the 7th day of AHN; in
      addition, all of the patients repeated all of the items at 6 months after herpes.
      CONCLUSIONS: The serum NINJ2 levels are associated with nerve injury,
      particularly with nerve recovery, and may be predictors of PHN occurrence.

PMID- 29069721
TI  - Evolutionary cancer-favoring engineered vaccinia virus for metastatic
      hepatocellular carcinoma.
AB  - Engineered vaccinia virus-based therapy shows promising results in patients with
      advanced hepatocellular carcinoma, although a strategic virus design for the
      metastatic liver and the study of its efficacy in treating the cancer has not
      been well assessed. In this paper, we proposed a simple and strategic virus
      design for targeting metastatic hepatocellular carcinoma. We developed an
      evolutionary cancer-favoring engineered vaccinia virus (CVV, which is produced by
      repeated selective replication in cancerous tissues and then deleting viral
      thymidine kinase genes) and investigated its therapeutic effects on metastatic
      liver cancer. The expression of the cell surface marker, CD44, which is
      associated with cancer stem cells, seems to be correlated with the cells'
      metastatic characteristics; cellular migration, epithelial-mesenchymal transition
      (EMT) expression and liver tumorigenicity. The highly metastatic and tumorigenic
      Sk-Hep-1 cell line was selected and injected directly onto the liver tissue to
      develop a liver-to-colon metastasis model. In an animal study, the subjects were
      treated with sorafenib, CVV, or sorafenib with CVV. Metastatic regions were
      interestingly rare in the CVV-treated groups (i.e., CVV or sorafenib with CVV)
      whereas metastatic regions existed in the sorafenib-treated group. From results,
      we concluded that our simple strategy of developing a cancer-favoring virus can
      successfully eradicate metastatic liver cancer cells, provided that our CVV can
      be a promising therapeutic virus that targets metastatic liver cancer.

PMID- 29069720
TI  - Reduced production and uptake of lactate are essential for the ability of WNT5A
      signaling to inhibit breast cancer cell migration and invasion.
AB  - Here we investigated the impact of WNT5A signaling on aerobic glycolysis and
      evaluated its effects on breast cancer cell migration/invasion. WNT5A signaling
      reduced migration and lactate production and caused selective down-regulation of
      the glycolytic enzyme phosphofructokinase platelet-type (PFKP). These events
      occurred in parallel with a WNT5A-induced inhibition of beta-catenin signaling.
      Support for essential involvement of beta-catenin and PFKP in lactate production
      and migration/invasion was obtained by siRNA knockdown of their expression. To
      also explore the effect of non-tumor cell-derived lactate, we added exogenous
      lactate to the cells and noted an increase in migration that was significantly
      impaired by recombinant WNT5A in parallel with a down-regulation of the lactate
      transporter monocarboxylate transporter 1 (MCT1). Interestingly enough, the drug
      candidate Foxy5 (WNT5A-mimic hexapeptide) also inhibited breast cancer cell
      migration in the presence of exogenous lactate, suggesting a therapeutic
      potential for Foxy5 in managing breast tumors with high glycolytic activity.
      Overall, we demonstrated that WNT5A signaling (via a beta-catenin-PFKP axis)
      reduces lactate production and lowers the expression of MCT1, a carrier mediating
      the uptake of lactate from the tumor microenvironment. These effects of WNT5A are
      essential for its ability to impair breast cancer migration/invasion even in an
      environment with elevated lactate levels.

PMID- 29069717
TI  - Integrated analysis of dosage effect lncRNAs in lung adenocarcinoma based on
      comprehensive network.
AB  - Accumulating evidences indicate that cancer-related lncRNAs occur frequent
      somatic copy number alternation (SCNA). Although individual SCNA lncRNAs have
      been implicated in tumor biology, their regulatory mechanism has not been
      assessed in a systematic way. In order to explore the expression characteristics
      and biological functions of SCNA lncRNAs in cancer, we built a computational
      framework based on lncRNA expression profiles, lncRNA copy numbers and dosage
      sensitivity score (DSS). First, we found that the lncRNAs with different DSS were
      involved in distinct biological processes, while those with the same DSS had
      similar functions. Second, some of the lncRNAs participated in the progression
      and metastasis of lung adenocarcinoma (LUAD) through cis-acting regulation. In
      lncRNA-TF-mRNA network, lncRNAs interacted with 4 TFs and affected the immune
      system, and further influenced LUAD progression. Third, competing endogenous RNA
      network analysis inferred that lncRNA ENSG00000240990 competed with HOXA10 to
      absorb hsa-let-7a/b/f/g-5p and affected patient prognosis in LUAD. Last but not
      least, by integrating target information of miRNA we also provided a new
      perspective for the discovery of potential small molecule drugs. In summary, we
      systematically analyzed the regulatory role of SCNA lncRNAs. This work may
      facilitate cancer research and serve as the basis for future efforts to
      understand the role of SCNA lncRNAs, develop novel biomarkers and improve
      knowledge of tumor biology.

PMID- 29069719
TI  - MUC2 mucin deficiency alters inflammatory and metabolic pathways in the mouse
      intestinal mucosa.
AB  - The mucus layer in the intestine affects several aspects of intestinal biology,
      encompassing physical, chemical protection, immunomodulation and growth, thus
      contributing to homeostasis. Mice with genetic inactivation of the Muc2 gene,
      encoding the MUC2 mucin, the major protein component of mucus, exhibit altered
      intestinal homeostasis, which is strictly dependent on the habitat, likely due to
      differing complements of intestinal microbes. Our previous work established that
      Muc2 deficiency was linked to low chronic inflammation resulting in tumor
      development in the small, large intestine including the rectum. Here, we report
      that inactivation of Muc2 alters metabolic pathways in the normal appearing
      mucosa of Muc2-/- mice. Comparative analysis of gene expression profiling of
      isolated intestinal epithelial cells (IECs) and the entire intestinal mucosa,
      encompassing IECs, immune and stromal cells underscored that more than 50% of the
      changes were common to both sets of data, suggesting that most alterations were
      IEC-specific. IEC-specific expression data highlighted perturbation of lipid
      absorption, processing and catabolism linked to altered Pparalpha signaling in
      IECs. Concomitantly, alterations of glucose metabolism induced expression of
      genes linked to de novo lipogenesis, a characteristic of tumor cells.
      Importantly, gene expression alterations characterizing Muc2-/- IECs are similar
      to those observed when analyzing the gene expression signature of IECs along the
      crypt-villus axis in WT B6 mice, suggesting that Muc2-/- IECs display a crypt
      like gene expression signature. Thus, our data strongly suggest that decreased
      lipid metabolism, and alterations in glucose utilization characterize the crypt
      proliferative compartment, and may represent a molecular signature of pre
      neoplastic lesions.

PMID- 29069722
TI  - Repression of SUMOylation pathway by grass carp reovirus contributes to the
      upregulation of PKR in an IFN-independent manner.
AB  - SUMOylation, a post-translational modification, is involved in interaction
      between hosts and viruses, and participates in diverse cellular processes
      including inflammatory responses and innate immunity. Here, we investigated the
      interaction between reovirus infection and the cellular SUMOylation machinery
      using grass carp reovirus (GCRV) as a model. Full-length cDNAs of grass carp SUMO
      1 and SUMO-2 were obtained and phylogenetic analysis indicated that they shared
      high homology with those of higher vertebrates. The two modifiers and SUMO
      conjugating enzyme 9 (Ubc9) were ubiquitously expressed in all tested tissues of
      grass carp. During GCRV infection in CIK cells, transcriptional expressions of
      SUMO1/2 and Ubc9 were significantly inhibited; while UV-inactivated GCRV failed
      to inhibit the expression of the three molecules, which suggested that
      SUMOylation system was suppressed during viral replication. In CIK cells treated
      with inhibitor 2-D08 for SUMOylation, GCRV replication was not interfered;
      however, transcriptional analysis of immune genes involved in anti-viral
      interferon (IFN) response indicated that IRF2 and PKR were significantly up
      regulated in CIK cells treated with inhibitor in contrast to IRF1, IRF7 and IFNI.
      Furthermore, 2-D08 treatment coupled with GCRV challenge resulted in higher IRF2
      and PKR level during infection in comparison to those of CIK cells infected with
      GCRV only. These results indicated that inhibition of SUMOylation should result
      in the induction of PKR via IFN-independent manner, and both IFN-signaling and
      IFN-independent signaling seemed to involve in the upregulation of PKR during the
      process of GCRV infection. Repression of SUMOylation by GCRV might represent a
      cellular antiviral mechanism.

PMID- 29069728
TI  - A single nucleotide polymorphism of AIRE gene located in the 21q22.3 increases
      the risk of rheumatoid arthritis.
AB  - Several studies addressed the association of autoimmune regulator (AIRE) gene
      polymorphism with the risk of rheumatoid arthritis (RA); however, their
      conclusions were inconsistent. For better investigating the effects of this
      polymorphism on the risk of RA, we conducted this study to evaluate the role of
      AIRE rs2075786 polymorphism in the risk of RA. Four eligible studies involving
      6,755 cases and 7,970 controls were identified by searching the databases of
      PubMed, CNKI and EMBASE up to February 2017. Our study revealed that AIRE
      rs2075786 polymorphism was associated with an increased risk of RA under all
      genetic models. In the subgroup analysis, AIRE rs2075786 polymorphism contributed
      to RA susceptibility among Asians, but not among Caucasians. To summarize,, this
      meta-analysis confirms that AIRE rs2075786 polymorphism may play a significant
      role in increasing the risk of RA. Stratification analysis by ethnicity reveals
      that AIRE rs2075786 polymorphism is associated with an increased risk of RA among
      Asians, but not among Caucasians. These findings need further validation in the
      large multicenter case-control studies.

PMID- 29069727
TI  - A global comparison of the cost of patented cancer drugs in relation to global
      differences in wealth.
AB  - INTRODUCTION: There are major differences in cancer drug prices around the world.
      However, the patterns of affordability of these drugs are poorly understood. The
      objective of this study was to compare patterns of affordability of cancer drugs
      in Australia, China, India, Israel, South Africa, the United Kingdom, and the
      United States. RESULTS: Cancer drug prices are highest in the United States.
      Cancer drugs are the least affordable in India by a large margin. Despite lower
      prices than in the USA, cancer drugs are less affordable in middle-income
      countries than in high-income countries. MATERIALS AND METHODS: We obtained the
      prices of a basket of cancer drugs in all 7 countries, and converted the prices
      to US$ using both foreign exchange rates and purchasing power parity. We assessed
      international differences in wealth by collecting values for gross domestic
      product (GDP) per capita in addition to average salaries. We compared patterns of
      affordability of cancer drugs by dividing the drug prices by the markers of
      wealth. CONCLUSIONS: Cancer drugs are less affordable in middle-income countries
      than in high-income countries. Differential pricing may be an acceptable policy
      to ensure global affordability and access to highly active anti-cancer therapies.

PMID- 29069729
TI  - Interleukin-35 expression is associated with colon cancer progression.
AB  - Colon cancer development is closely related to inflammation. Thus, we conducted
      the present investigation to study the effects of IL-35 (Interleukin 35), a newly
      identified anti-inflammatory factor, on colon cancer development. We first
      evaluated the IL-35 expression in 186 pairs of colon cancer samples and paired
      adjacent normal tissues by qPCR, ELISA (Enzyme-linked immunoassay) and tissue
      microarrays. Then the role of IL-35 on patient survival rates, colon cancer
      progression and their sensitivity to chemotherapy drugs were assessed. IL-35 was
      barely expressed in the colon cancer tissue but highly expressed in the adjacent
      normal tissue. The down-regulation of IL-35 was significantly associated with the
      AJCC (American Joint Committee on Cancer) stage, nodal involvement, invasion
      depth, distant metastasis, differentiation and it was also shown to be an
      independent prognostic indicator of both disease-free and overall survivals for
      colon cancer patients. Overexpression of IL-35 in colon cancer cell suppressed
      cell migration, invasion, proliferation, colony formation and cancer stem cells
      through suppressing beta-catenin. IL-35 inhibited colon tumor formation in the
      mice model and sensitize the cancer cell to chemotherapy drugs. Our results
      showed that IL-35 shows an inhibitory effect in colon cancer development and is a
      novel prognostic indicator. Therefore, IL-35 might be a potential therapeutic
      target.

PMID- 29069726
TI  - TUBB3 overexpression has a negligible effect on the sensitivity to taxol in
      cultured cell lines.
AB  - Microtubules are cellular targets for a variety of anticancer therapies because
      of their critical function in mitosis. Taxol belongs to a class of microtubule
      targeting agents that suppresses microtubule dynamics and interferes with the
      functioning of the mitotic spindle, thereby effectively blocking cell cycle
      progression of rapidly proliferating tumor cells. Despite its antitumor activity,
      drug resistance remains a common obstacle in improving its overall clinical
      efficacy. Previous studies have shown that the expression of a specific beta
      tubulin isotype, betaIII-tubulin/TUBB3, is dysregulated in drug-refractory
      tumors. However, whether enhanced TUBB3 expression is directly involved in
      promoting taxol resistance remains a subject of debate. Here, we have used
      several approaches to assess the functional relation of TUBB3 overexpression and
      taxol resistance. First, we generated a number of taxol-resistant cell lines, to
      find that TUBB3 expression was elevated in a resistant cell line (RPE-20) derived
      from untransformed retinal pigment epithelial (RPE) cells, but the abundance of
      TUBB3 remained unchanged in four other cell lines after taxol treatment. However,
      although RPE-20 cells displayed enhanced TUBB3 levels, we find that simultaneous
      up-regulation of the P-glycoprotein (P-gP) drug-efflux pump is responsible for
      the resistance to taxol. Indeed, we could show that TUBB3 levels were dynamically
      regulated upon taxol exposure and withdrawal, unrelated to the resistance
      phenotype. Next, we generated cell lines in which we could induce robust
      overexpression of TUBB3 from its endogenous locus employing the CRISPRa system.
      We demonstrate that solely enhancing TUBB3 expression results in a very minor
      decrease in the sensitivity to taxol. This was further substantiated by selective
      depletion of TUBB3 in a series of breast cancer cell lines expressing high levels
      of TUBB3. We find that TUBB3 depletion had a minimal effect on the sensitivity to
      taxol in one of these cell lines, but had no effect in all of the others. Based
      on these findings we propose that TUBB3 overexpression can only marginally affect
      the sensitivity to taxol in cultured cell lines.

PMID- 29069723
TI  - Repurposing Albendazole: new potential as a chemotherapeutic agent with
      preferential activity against HPV-negative head and neck squamous cell cancer.
AB  - Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer
      properties, however its activity in head and neck squamous cell cancer (HNSCC)
      was unknown. Using a series of in vitro assays, we assessed the ability of
      albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of
      albendazole doses (1 nM-10 MUM). Cell lines that responded to treatment were
      further examined for cell death, inhibition of migration and cell cycle arrest.
      Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to
      albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human
      papillomavirus-positive HNSCC cell lines responded. Albendazole treatment
      resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the
      G2/M phase and altered tubulin distribution. Normal control cells were not
      measurably affected by any dose tested. This study indicates that albendazole
      acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell
      lines and thus warrants further study as a potential chemotherapeutic agent for
      patients suffering from head and neck cancer.

PMID- 29069731
TI  - Profiling and bioinformatic analysis of circular RNA expression regulated by c
      Myc.
AB  - The c-Myc transcription factor is involved in cell proliferation, cell cycle and
      apoptosis by activating or repressing transcription of multiple genes. Circular
      RNAs (circRNAs) are widely expressed non-coding RNAs participating in the
      regulation of gene expression. Using a high-throughput microarray assay, we
      showed that Myc regulates the expression of certain circRNAs. A total of 309 up-
      and 252 down-regulated circRNAs were identified. Among them, randomly selected 8
      circRNAs were confirmed by real-time PCR. Subsequently, Myc-binding sites were
      found to generally exist in the promoter regions of differentially expressed
      circRNAs. Based on miRNA sponge mechanism, we constructed circRNAs/miRNAs network
      regulated by Myc, suggesting that circRNAs may widely regulate protein expression
      through miRNA sponge mechanism. Lastly, we took advantage of Gene Ontology and
      KEGG analyses to point out that Myc-regulated circRNAs could impact cell
      proliferation through affecting Ras signaling pathway and pathways in cancer. Our
      study for the first time demonstrated that Myc transcription factor regulates the
      expression of circRNAs, adding a novel component of the Myc tumorigenic program
      and opening a window to investigate the function of certain circRNAs in
      tumorigenesis.

PMID- 29069733
TI  - CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation
      through p53 pathway.
AB  - CDK1 (cyclin-dependent kinase 1) is a critical regulator of the G2-M checkpoint.
      CDK1 is considered a possible target for cancer treatment. In addition to CDK1,
      iASPP plays essential role in maintaining cancer cell proliferation. In the
      present study, we monitored the expression of CDK1 and iASPP at mRNA and protein
      levels in CRC tissues and cell lines; we also predicted that iASPP protein might
      interact with CDK1 protein. By performing GST pull-down assay and Co-IP assay, we
      confirmed the interaction of CDK1 and iASPP protein. In CRC cell lines, CDK1
      interacted with iASPP to affect CRC cell proliferation and apoptosis; moreover,
      the p53 apoptosis pathway was involved in this progression. Taken together, we
      revealed that CDK1 and iASPP was up-regulated in CRC tissues and cell lines; CDK1
      protein interacted with iASPP protein to affect CRC cell proliferation and
      apoptosis through the p53 apoptosis pathway. CDK1 and iASPP might serve as not
      only promising targets in CRC treatment, but also efficient prognostic markers.
      From the perspective of protein interactions, we provided a novel theoretical
      basis for targeted therapy of CRC.

PMID- 29069732
TI  - Characterization of the transcriptional and metabolic responses of pediatric high
      grade gliomas to mTOR-HIF-1alpha axis inhibition.
AB  - Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse
      intrinsic pontine gliomas, are known to have a very dismal prognosis. For
      instance, even an increased knowledge on molecular biology driving this brain
      tumor entity, there is no treatment able to cure those patients. Therefore, we
      were focusing on a translational pathway able to increase the cell resistance to
      treatment and to reprogram metabolically tumor cells, which are, then, adapting
      easily to a hypoxic microenvironment. To establish, the crucial role of the
      hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic
      deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured
      in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi
      therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1alpha (irinotecan), we
      hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF
      1alpha/HIF-2alpha/MYC proteins or genes may provide a modulation of the cell
      response to this double targeting. Finally, we could evidence three protein,
      genomic and metabolomic profiles of response to rapamycin combined with
      irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1alpha targeting
      was linked to a MYC/ERK/HIF-1alpha over-expression and the cell resistance to a
      major hyper-expression of HIF-2alpha.

PMID- 29069739
TI  - A nation-wide retrospective epidemiological study of gastroenteropancreatic
      neuroendocrine neoplasms in china.
AB  - BACKGROUND: Representative data on the gastroenteropancreatic neuroendocrine
      neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study
      aims to create a GEP-NENs profile of Chinese patients. METHODS: This was a
      hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective
      study which collected GEP-NEN patients' information in tertiary referral
      hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the
      selected hospitals were included. The primary GEP-NEN sites were measured and the
      epidemiological and clinical information of each tumor site were compared.
      RESULTS: The most common primary sites for GEP-NEN were the pancreas (31.5%) and
      rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small
      intestinal and colonic NENs took up a relatively small proportion of all
      patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs,
      tended to be found in younger (P<0.001), female (P<0.001), urban (P<0.001)
      residents with a higher education level (P=0.032) and were also diagnosed at
      earlier stage (P<0.001) and lower grade (P<0.001). Surgery remained the primary
      treatment method in all groups. CONCLUSIONS: More studies on the commonality and
      heterogeneity of GEP-NENs are warranted to improve diagnosis efficiencies and
      treatment outcomes.

PMID- 29069725
TI  - Notch4 and mhc class II polymorphisms are associated with hcv-related benign and
      malignant lymphoproliferative diseases.
AB  - Mixed cryoglobulinemia (MC), is a HCV-related, clinically benign,
      lymphoproliferative disorder (LPD) that may evolve into a non Hodgkin's lymphoma
      (NHL). Significant associations were found between two single nucleotide
      polymorphisms near NOTCH4 (rs2071286) and the HLA class II (rs9461776) genes and
      HCV-related MC syndrome (MCS). We analyzed NOTCH4 rs2071286 and HLA-II rs9461776
      in 3 HCV-related LPD groups (asymptomatic MC, MCS, NHL) with HCV infection
      without lymphoproliferative disorders. We found a positive relationship between
      NOTCH4 rs207186 T minor allele frequency (MAF) and patients with HCV-related LPDs
      at risk of NHL (Chi-square test for trend = 14.84 p = 0.0001), in accordance with
      an over-dominant model in the NHL group (CT vs CC + TT, OR=1.88, 95% CI 1.24
      2.83, p = 0.0026). Regarding HLA II rs9461776, G MAF increased in patients with
      HCV-related LPDs at risk of NHL (Chi-square test for trend = 8.40 p = 0.0038), in
      accordance with a recessive genotypic model in the NHL group (G/G vs A/A + A/G,
      OR = 11.07, 95% CI 2.37-51.64, p = 0.0022). Both NOTCH4 rs2071286 and HLA-II
      rs9461776 were present on chromosome 6 and showed D' and r values of linkage
      disequilibrium (LD) of about 0.5 values, thereby suggesting there is no extensive
      LD in the HCV+ population. This data shows that the previously demonstrated
      association between NOTCH4 rs2071286 and HLA-II rs9461776 polymorphisms and HCV
      related MCS could be extended to overall patients with HCV-related LPDs. The
      significant relationship between rs2071286 and rs9461776 MAF and the increased
      risk for NHL, suggests their use as non-invasive markers to categorize patients
      at risk of lymphoma.

PMID- 29069738
TI  - Hematopoietic transcription factors and differential cofactor binding regulate
      PRKACB isoform expression.
AB  - Hematopoietic differentiation is controlled by key transcription factors, which
      regulate stem cell functions and differentiation. TAL1 is a central transcription
      factor for hematopoietic stem cell development in the embryo and for gene
      regulation during erythroid/megakaryocytic differentiation. Knowledge of the
      target genes controlled by a given transcription factor is important to
      understand its contribution to normal development and disease. To uncover direct
      target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin
      precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP
      promoter arrays. We identified 451 TAL1 target genes in K562 cells. Furthermore,
      we analysed the regulation of one of these genes, the catalytic subunit beta of
      protein kinase A (PRKACB), during megakaryopoiesis of K562 and primary human
      CD34+ stem cell/progenitor cells. We found that TAL1 together with hematopoietic
      transcription factors RUNX1 and GATA1 binds to the promoter of the isoform 3 of
      PRKACB (Cbeta3). During megakaryocytic differentiation a coactivator complex on
      the Cbeta3 promoter, which includes WDR5 and p300, is replaced with a corepressor
      complex. In this manner, activating chromatin modifications are removed and
      expression of the PRKACB-Cbeta3 isoform during megakaryocytic differentiation is
      reduced. Our data uncover a role of the TAL1 complex in controlling differential
      isoform expression of PRKACB. These results reveal a novel function of TAL1,
      RUNX1 and GATA1 in the transcriptional control of protein kinase A activity, with
      implications for cellular signalling control during differentiation and disease.

PMID- 29069737
TI  - Functional heterogeneity in tumor-derived human pancreatic stellate cells:
      Differential expression of HGF and implications for mitogenic signaling and
      migration in pancreatic cancer cells.
AB  - The pancreatic stellate cell (PSC) is the principal cell type of the desmoplastic
      stroma of pancreatic ductal adenocarcinoma (PDAC). PSCs interact with cancer
      cells and influence the progression of the disease through a complex network of
      signaling molecules including hepatocyte growth factor (HGF). Functional
      heterogeneity of PSCs within a tumor might conceivably influence tumor
      progression. We investigated PSC populations isolated from different human PDACs
      and examined the effects of PSC-conditioned medium on BxPC-3 and AsPC-1
      pancreatic cancer cells. The different PSC populations exhibited a wide range of
      variation (120-3,000 pg/ml) in their ability to secrete HGF. Media from high-HGF
      producing PSCs stimulated phosphorylation of Met, Gab1, and ERK in the cancer
      cells and induced increases in DNA synthesis and migration which were blocked by
      the Met inhibitor SU11274, indicating a role of HGF as a mediator. HGF levels
      produced by PSCs and the effects of PSC media on the cancer cells were increased
      by IL-1alpha and inhibited by TGFbeta. The functional heterogeneity of PSCs in
      terms of HGF-mediated tumor-stroma interactions suggests that inhibition of the
      HGF pathway as a novel treatment approach in PDAC might have different effects in
      different subsets of patients.

PMID- 29069740
TI  - Blockage of FOXP3 transcription factor dimerization and FOXP3/AML1 interaction
      inhibits T regulatory cell activity: sequence optimization of a peptide
      inhibitor.
AB  - Although T regulatory cells (Treg) are essential for the prevention of autoimmune
      diseases, their immunoregulatory function restrains the induction of immune
      responses against cancer. Thus, development of inhibitors of FOXP3, a key
      transcription factor for the immunosuppressive activity of Treg, might give new
      therapeutic opportunities. In a previous work we identified a peptide (named P60)
      able to enter into the cells, bind to FOXP3, and impair Treg activity in vitro
      and in vivo. Here we show that P60 binds to the intermediate region of FOXP3 and
      inhibits its homodimerization as well as its interaction with the transcription
      factor AML1. Alanine-scanning of P60 revealed the relevance of each position on
      FOXP3 binding, homodimerization, association with AML1 and inhibition of Treg
      activity. Introduction of alanine at positions 2, 5 and 11 improved the activity
      of the original P60, whereas alanine mutations at positions 1, 7, 8, 9, 10 and 12
      were detrimental. Multiple mutation experiments allowed us to identify peptides
      with higher FOXP3 binding affinity and stronger biological activity than the
      original P60. Head to tail macrocyclization of peptide P60-D2A-S5A improved Treg
      inhibition and enhanced anti-tumor activity of anti-PD1 antibodies in a model of
      hepatocellular carcinoma. Introduction of a D-aminoacid at position 2 augmented
      significantly microsomal stability while maintained FOXP3 binding capacity and
      Treg inhibition in vitro. In vivo, when combined with the cytotoxic T-cell
      epitope AH1, it induced protection against CT26 tumor implantation. This study
      provides important structure-function relationships essential for further drug
      design to inhibit Treg cells in cancer.

PMID- 29069734
TI  - MGr1-Antigen/37 kDa laminin receptor precursor promotes cellular prion protein
      induced multi-drug-resistance of gastric cancer.
AB  - Cellular prion protein (PrPC), the infective agent of transmissible spongiform
      encephalopathies, is thought to be related to several cellular physiological and
      physiopathological processes. We have previously reported that PrPC participates
      in multi-drug-resistance of gastric cancer. As the salient ligand molecule of PrP
      for participating in internalization and propagation of the scrapie form of prion
      protein (PrPSc), 37 kDa laminin receptor precursor protein (37LRP) shared the
      same gene coding sequence of MGr1-Ag, another protein previously found to be
      involved in multi-drug-resistance of gastric cancer in our lab. In the present
      study, we explored whether MGr1-Ag/37LRP contributed to PrPC mediated multi-drug
      resistance in gastric cancer. Immunohistochemical staining showed similar
      expression patterns of MGr1-Ag/37LRP and PrPC in gastric cancer tissue serial
      sections. Western blot and immunohistochemistry also demonstrated correlative
      expression of MGr1-Ag/37LRP and PrPC in gastric cancer cell lines. Interaction
      between MGr1-Ag/37LRP and PrPC in gastric cancer cell lines and gastric cancer
      tissues were verified by immunofluorescence and co-immunoprecipitation.
      Furthermore, knockdown of MGr1-Ag/37LRP significantly attenuated PrPC induced
      multi-drug-resistance by sensitizing drug-induced apoptosis through inhibition of
      AKT activation. In conclusion, MGr1-Ag/37LRP may interact with PrPC and promote
      the PrPC induced multi-drug-resistance in gastric cancer through PI3K/AKT
      pathway. The current study elucidates the mechanism of how PrPC triggers
      intracellular signaling cascade resulting in multi-drug-resistance phenotype and
      provides a novel candidate molecular target against gastric cancer.

PMID- 29069730
TI  - Inhibition of colorectal cancer genomic copy number alterations and chromosomal
      fragile site tumor suppressor FHIT and WWOX deletions by DNA mismatch repair.
AB  - Homologous recombination (HR) enables precise DNA repair after DNA double strand
      breaks (DSBs) using identical sequence templates, whereas homeologous
      recombination (HeR) uses only partially homologous sequences. Homeologous
      recombination introduces mutations through gene conversion and genomic deletions
      through single-strand annealing (SSA). DNA mismatch repair (MMR) inhibits HeR,
      but the roles of mammalian MMR MutL homologues (MLH1, PMS2 and MLH3) proteins in
      HeR suppression are poorly characterized. Here, we demonstrate that mouse
      embryonic fibroblasts (MEFs) carrying Mlh1, Pms2, and Mlh3 mutations have higher
      HeR rates, by using 7,863 uniquely mapping paired direct repeat sequences (DRs)
      in the mouse genome as endogenous gene conversion and SSA reporters.
      Additionally, when DSBs are induced by gamma-radiation, Mlh1, Pms2 and Mlh3
      mutant MEFs have higher DR copy number alterations (CNAs), including DR CNA
      hotspots previously identified in mouse MMR-deficient colorectal cancer (dMMR
      CRC). Analysis of The Cancer Genome Atlas CRC data revealed that dMMR CRCs have
      higher genome-wide DR HeR rates than MMR proficient CRCs, and that dMMR CRCs have
      deletion hotspots in tumor suppressors FHIT/WWOX at chromosomal fragile sites
      FRA3B and FRA16D (which have elevated DSB rates) flanked by paired homologous DRs
      and inverted repeats (IR). Overall, these data provide novel insights into the
      MMR-dependent HeR inhibition mechanism and its role in tumor suppression.

PMID- 29069742
TI  - UBE2J2 promotes hepatocellular carcinoma cell epithelial-mesenchymal transition
      and invasion in vitro.
AB  - Ubiquitin-conjugating enzyme E2 J2 (UBE2J2) is an ubiquitin proteasome component
      that responds to proteotoxic stress. We found that UBE2J2 was highly expressed in
      cellular protrusions of HCCLM3 metastatic hepatocellular carcinoma (HC) cells.
      Immunohistochemical analyses showed that UBE2J2 was expressed at higher levels in
      HC patient tissues than in corresponding non-tumor tissues. Because cellular
      protrusions are important for cell invasion, we hypothesized that UBE2J2 promotes
      HC cell invasion. We used chip-based surface plasmon resonance (SPR) to assess
      possible mechanisms of UBE2J2-regulated HCCLM3 cell invasion. We found that p
      EGFR interacted with UBE2J2, and this finding was confirmed by co
      immunoprecipitation analysis. UBE2J2 overexpression activated endothelial
      mesenchymal transition in the non-invasive SMMC7721 HC cell line, and promoted
      invasion. UBE2J2 silencing reduced HCCLM3 cell invasion and endocytosis, and
      downregulated p-EGFR expression. p-EGFR inhibition by lapatinib reduced UBE2J2
      promoted cell invasion, suggesting p-EGFR is important for UBE2J2-mediated HCCLM3
      cell invasion. These findings demonstrate that endocytosis by HC cells is closely
      related to invasion, and may provide new anti-HC therapeutic targets. UBE2J2 may
      also be a novel biomarker for clinical HC diagnosis.

PMID- 29069736
TI  - A novel synthetic derivative of quercetin, 8-trifluoromethyl-3,5,7,3',4'-O
      pentamethyl-quercetin, inhibits bladder cancer growth by targeting the AMPK/mTOR
      signaling pathway.
AB  - Quercetin is a naturally existing compound and shows attractive anticancer
      properties for a variety of solid tumors including glioma, bladder cancer,
      hepatocellular carcinoma, breast cancer, hematological malignancies and prostate
      carcinoma. However, these anticancer properties have not been clinically approved
      due to unclear mechanistic information and its low bioactivity. In our previous
      study, we elucidated that quercetin activates AMPK pathway which is the major
      mechanism for its unique anticancer effect in bladder cancer. In the present
      study, we are trying to enhance its bioactivity by chemical modification using
      fluorination approach to prepare novel chemical entities, based on the principle
      of intermediate derivative method (IDM). The compound we obtained is named 8
      trifluoromethyl-3,5,7,3',4'-O-pentamethyl- quercetin (TFQ), characterized by NMR
      spectra and mass spectrum (MS). The results from MTT and cologenic assay in two
      human and one murine bladder cancer cell lines showed that TFQ exhibits more
      potent inhibition on the three bladder cancer cell lines than quercetin (Que)
      although this enhanced effects is not very dramatic. Furthermore, we found that
      the survival of normal bladder cells PEBC was not significantly suppressed by TFQ
      compared with Que. Western blot analysis showed that TFQ possess more potent AMPK
      activation than Que. The downstream of AMPK was further examined by western blot.
      TFQ treatment is able to inactivate mTOR signaling pathway with the regulation of
      mTOR, 4EBP1 and P70S6K. These results demonstrated that the fluorinated quercetin
      derivative TFQ inhibits bladder cancer cell growth through the AMPK/mTOR pathway.
      Altogether, our findings suggest that TFQ could serve as a new potential
      therapeutic agent for bladder cancer more effective than Que.

PMID- 29069735
TI  - HMGB1-mediated autophagy attenuates gemcitabine-induced apoptosis in bladder
      cancer cells involving JNK and ERK activation.
AB  - High-mobility group box 1 (HMGB1) has been found to mediate autophagy during
      chemotherapy in several cancers. However, whether HMGB1plays a role in autophagy
      and chemoresistance in bladder cancer is elusive. In this report, HMGB1
      expression was found to be increased in 30 primary bladder cancer tissue
      specimens compared to their matched adjacent non-tumor tissues. While gemcitabine
      induced apoptotic cell death, it also induced HMGB1 expression and autophagy in
      bladder cancer T24 and BIU-87 cells. Suppressing HMGB1 expression with siRNA
      strongly potentiated gemcitabine-induced apoptosis. HMGB1 siRNA or autophagy
      inhibitors suppressed gemcitabine-induced autophagy. Further, gemcitabine
      activated c-Jun N-terminal kinase (JNK) and extracellular regulated protein
      kinase (ERK) and Bcl-2 phosphorylation, and blocking ERK and JNK inhibited
      autophagy and increased apoptosis in gemcitabine-treated cells. Interestingly,
      suppressing HMGB1 expression attenuated gemcitabine-induced ERK and JNK
      activation and Bcl-2 phosphorylation. Thus, our results suggest that while
      gemcitabine kills bladder cancer cells through apoptosis, a cytoprotective
      autophagy is also induced involving HMGB1-mediated JNK and ERK to counteract the
      cytotoxicity of gemcitabine, and intervention targeting this pathway may improve
      the anticancer efficacy of gemcitabine against bladder cancer.

PMID- 29069741
TI  - B7-H3 promotes gastric cancer cell migration and invasion.
AB  - B7-H3 (B7 homologue 3, CD276) is a member of the B7 immunoregulatory family and
      promotes tumor progression. The present study demonstrated that B7-H3 promotes
      gastric cancer cell migration and invasion. shRNA-mediated B7-H3 silencing in the
      N87 gastric cancer cell line suppressed cell migration and invasion in vitro and
      in vivo; downregulated metastasis-associated CXCR4; and inhibited AKT, ERK, and
      Jak2/Stat3 phosphorylation. B7-H3-silenced cells injected into the tail veins of
      4-week-old female BALB/c nude mice produced fewer metastases than control cells,
      and resulted in longer survival times. Immunofluorescence analyses confirmed B7
      H3/CXCR4 colocalization in N87 cells, and co-immunoprecipitation assays showed a
      direct interaction between the two proteins. Our analysis of 120 tissue samples
      from gastric cancer patients showed that increased B7-H3 expression correlated
      positively with both tumor infiltration depth and CXCR4 expression. These
      findings suggest that B7-H3 and CXCR4 may be novel targets for anti-gastric
      cancer therapeutics.

PMID- 29069746
TI  - WX-132-18B, a novel microtubule inhibitor, exhibits promising anti-tumor effects.
AB  - Cancer drug researchers have been seeking microtubule-inhibiting agents (MIAs)
      with higher bioactivity and lower toxicity than currently marketed drugs. WX-132
      18B, a novel structural compound synthesized at our institute, specifically bound
      to the colchicine-binding site on tubulin rather than the vinblastine site, and
      concentration-dependently reduced microtubule content via depolymerization. It
      exhibited the same cellular phenotypic profiles as the classic MIAs (colchicine,
      vincristine, and taxol), including inducing cell cycle arrest at the G2/M phase,
      triggering tumor cell apoptosis, promoting nuclear membrane permeability,
      reducing mitochondrial membrane potential, and disrupting the redox system
      balance. Importantly, WX-132-18B displayed more potent in vitro bioactivity (IC50
      0.45-0.99 nM) than did the classic MIAs; it inhibited the proliferation of human
      umbilical vein endothelial cells and seven types of human tumor cells, especially
      the taxol-resistant breast cancer cells MX-1/T. WX-132-18B also dose-dependently
      inhibited mice sarcoma, human lung, and gastric cancer xenograft tumors and the
      formation of tumor blood vessels in mice. In conclusion, WX-132-18B is a novel
      microtubule-depolymerizing agent that selectively acts on the colchicine-binding
      site of tubulin and exerts potent in vitro and in vivo anti-tumor effects. These
      characteristics, along with its anti-angiogenesis and anti-drug resistance
      properties, make WX-132-18B a promising anti-tumor drug candidate.

PMID- 29069743
TI  - Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in
      IgA nephropathy in a northwest Chinese Han population.
AB  - IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis
      worldwide, but etiology and pathogenesis continue to be poorly understood.
      Polymorphisms in the cytokine genes may play a role in the etiology and
      pathogenesis of IgAN. The incidence of different between diverse ethnic groups
      suggested important genetic influences on its pathogenesis. We genotype 10 single
      nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY
      technology from 417 IgAN patients and 463 healthy controls of the Chinese Han
      population. We evaluated these SNPs associated with IgAN utilising the chi-square
      tests and genetic model analysis. We identified that the minor alleles of rs16944
      ("A"), rs1800796 ("G") in IL-1B, IL-6 were involved in an increasingly risk of
      IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796
      in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33
      fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN,
      respectively. There was only rs1800796 still correlated with IgAN in the allelic
      model after adjustment by age and gender and the Bonferroni correction. In
      addition, Haplotype Grs1800796A rs2069837G rs2069840 (P = 0.037) and G rs1800796A
      rs2069837C rs2069840 (P = 0.042) in IL-6were considered to be associated with
      increased IgAN risk. This study verified the IL-6, IL-1B genetic variants
      polymorphisms contributed to IgAN susceptibility in a Chinese Han population.
      Although we identified SNPs susceptibility, however, replication studies and
      functional research are required to confirm the genetic contribution in IgAN.

PMID- 29069750
TI  - AG488 as a therapy against gliomas.
AB  - High-grade gliomas such as glioblastomas (GBM) present a deadly prognosis
      following diagnosis and very few effective treatment options. Here, we
      investigate if the small molecule AG488 can be an effective therapy against GBM
      with both anti-angiogenic as well as an anti-microtubule inhibiting modalities,
      using a human G55 glioma xenograft model in nude mice. From in vitro studies, we
      report that AG488 incubation reduced cell viability in G55 and HMEC-1 cells more
      so than TMZ treatment, and AG488 treatment also decreased cell viability in
      normal astrocytes, but not as much as for G55 cells (p<0.0001). In vivo
      investigations indicated that AG488 therapy helped reduce tumor volumes
      (p<0.0001), prolong survival (p<0.01), increase tumor perfusion (p<0.01), and
      decrease microvessel density (MVD) (p<0.05), compared to untreated mice or mice
      treated with non-specific IgG, in the G55 xenograft model. Additionally, AG488
      did not induce apoptosis in normal mouse brain tissue. Animal survival and tumor
      volume changes for AG488 were comparable to TMZ or anti-VEGF therapies, however
      AG488 was found to be more effective in decreasing tumor-related vascularity
      (perfusion and MVD). AG488 is a potential novel therapy against high-grade
      gliomas.

PMID- 29069744
TI  - Eight potential biomarkers for distinguishing between lung adenocarcinoma and
      squamous cell carcinoma.
AB  - Lung adenocarcinoma (LADC) and squamous cell carcinoma (LSCC) are the most common
      non-small cell lung cancer histological phenotypes. Accurate diagnosis
      distinguishing between these two lung cancer types has clinical significance. For
      this study, we analyzed four Gene Expression Omnibus (GEO) datasets (GSE28571,
      GSE37745, GSE43580, and GSE50081). We then imported the datasets into the Gene
      Cloud of Biotechnology Information online platform to identify genes
      differentially expressed in LADC and LSCC. We identified DSG3 (desmoglein 3),
      KRT5 (keratin 5), KRT6A (keratin 6A), KRT6B (keratin 6B), NKX2-1 (NK2 homeobox
      1), SFTA2 (surfactant associated 2), SFTA3 (surfactant associated 3), and TMC5
      (transmembrane channel-like 5) as potential biomarkers for distinguishing between
      LADC and LSCC. Receiver operating characteristic curve analysis suggested that
      KRT5 had the highest diagnostic value for discriminating between these two cancer
      types. Using the PrognoScan online survival analysis tool and the Kaplan-Meier
      Plotter, we found that high KRT6A or KRT6B levels, or low NKX2-1, SFTA3, or TMC5
      levels correlated with unfavorable prognoses in LADC patients. Further studies
      will be needed to verify our findings in additional patient samples, and to
      elucidate the mechanisms of action of these potential biomarkers in non-small
      cell lung cancer.

PMID- 29069745
TI  - Down-regulation of MRPS23 inhibits rat breast cancer proliferation and
      metastasis.
AB  - Mitochondrial ribosomal protein S23 (MRPS23) has been shown to be involved in
      breast cancer cell proliferation and metastatic phenotypes of cervical cancer.
      Here we investigated its biological features in breast cancer for the first time.
      It demonstrated that knockdown of MRPS23 reduced breast cancer cell proliferation
      and induced apoptosis in vitro. Besides, shRNA targeting MRPS23 (shMRPS23)
      inhibited tumour proliferation and metastasis by blocking tumor angiogenesis in
      breast cancer xenograft rat model. Small animal positron emission
      tomography/computed tomography (PET/CT) with 2'-deoxy-2'-[18F] fluoro-D-glucose
      (FDG) was performed at four weeks after tumour cell injection. We found that FDG
      maximum standardized uptake value (SUVmax) significantly decreased by 31 +/- 3%
      in the shMRPS23-treated group. But this change was not independent of metabolic
      tumour size. In addition, we also found that shMRPS23 could significantly
      suppress breast cancer metastasis through inhibiting epithelial mesenchymal
      transition (EMT) phenotype. The epithelial marker E-cadherin was increased,
      whereas the metastasis associated gene vimentin was decreased. Mechanistically,
      shMRPS23-treated tumours failed to progress through p53 and p21WAF1/CIP1
      activation, but not cytochrome c-mediated pathway. These findings suggest that
      MRPS23 is a potential therapeutic target for interference of breast cancer
      proliferation, angiogenesis and metastasis.

PMID- 29069747
TI  - Renal cell carcinoma histological subtype distribution differs by age, gender,
      and tumor size in coastal Chinese patients.
AB  - The distribution pattern of renal cell carcinoma (RCC) histological subtypes
      according to age, gender and tumor size has not been well illustrated in RCC
      patients living in fast-developing regions of China. We recruited 2941 patients
      with clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma
      (PCC) or chromophobe from two hospitals in coastal China (2004-2012)
      consecutively and draw 538 American Chinese RCC patients' data with time matched
      from the Surveillance, Epidemiology, and End Results database. We found that
      compared with ccRCC patients, chromophobe patients were more likely to be female
      (OR: 2.538, 95% CI: 1.923-3.350), younger (OR for 51-60 years old: 0.686; OR for
      over 60 years old: 0.478; reference: age < 50) and to have a larger maximal
      diameter (Dmax) (OR for Dmax > 7 cm: 1.883; reference: Dmax <= 4 cm). Besides, in
      comparison with coastal Chinese patients, American Chinese individuals had lower
      Fuhrman grades (P < 0.001) and had an onset age 10 years delay. In conclusion, we
      were the first to observe marked gender, age and tumor size differences in the
      proportional subtype distribution of RCCs in coastal Chinese patients, and also
      the first to compare coastal Chinese with American Chinese data.

PMID- 29069749
TI  - In vitro and in vivo cytotoxic activity of human lactoferricin derived antitumor
      peptide R-DIM-P-LF11-334 on human malignant melanoma.
AB  - Di-peptides derived from the human host defense peptide lactoferricin were
      previously described to specifically interact with the negatively charged lipid
      phosphatidylserine exposed by cancer cells. In this study one further derivative,
      namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in
      vitro and in vivo while non-neoplastic cells are not harmed. In liposomal model
      systems composed of phosphatidylserine mimicking cancerous and
      phosphatidylcholine mimicking non-cancerous membranes the specific interaction
      with the cancer marker PS was confirmed by specific induction of membrane
      perturbation and permeabilization in presence of the peptide. In vitro studies
      with cell lines of human malignant melanoma, such as A375, or primary cells of
      human melanoma metastases to the brain, as MUG Mel1, and non-neoplastic human
      dermal fibroblasts NHDF revealed high cytotoxic effect of R-DIM-P-LF11-334 on
      melanoma cells of A375 and MUG Mel1, whereas only minor effect on the dermal
      fibroblasts NHDF was observed, yielding an about 20-fold killing-specificity for
      A375 and MUG-Mel1. The LC50 values for melanoma A375 and MUG Mel1 were about 10
      MUM. Analysis of secondary structure of the peptide revealed an increase in the
      proportion of beta-sheets exclusively in presence of the cancer mimic. Stability
      studies further indicated a potential adequate stability in blood or under
      stringent conditions. Importantly the cytotoxic effect on cancer cells was also
      proven in vivo in mouse xenografts of human melanoma, where peptide treatment
      induced strong tumor regression and in average a tumor area reduction of 85%
      compared to tumors of control mice without peptide treatment.

PMID- 29069751
TI  - A peptide antagonist of Prep1-p160 interaction improves ceramide-induced insulin
      resistance in skeletal muscle cells.
AB  - Prep1 is a homeodomain transcription factor belonging to the TALE protein family.
      Its overexpression affects glucose metabolism in several tissues. In particular,
      in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs
      GLUT4 expression and glucose uptake. In this study, we show that ceramides
      (C2cer), a class of lipids antagonizing insulin signalling, increase the levels
      of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce
      their association by 80%. We find that C2cer exposure inhibits insulin receptor,
      IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and
      glucose uptake by 1.3- and 2.1-fold, respectively. The synthetic Prep1(54-72)
      peptide, mimicking the Prep1 region involved in the interaction with p160,
      reduces in vitro Prep1-p160 binding in a dose-dependent way (IC50 = 0.20MUM). In
      C2cer-treated L6 cells, 10MUM Prep1(54-72) restores insulin signalling impaired
      by ceramide treatment. Prep1 overexpressing L6 cells display similar metabolic
      alterations observed in ceramide-treated L6 cells and the presence of Prep1(54
      72) mitigates these events. All these findings suggest that disruption of the
      Prep1/p160 molecular interaction enhances insulin sensitivity impaired by
      ceramides in skeletal muscle cells and indicate this complex as an important
      target for type 2 diabetes.

PMID- 29069748
TI  - Clinical impact of high serum hepatocyte growth factor in advanced non-small cell
      lung cancer.
AB  - Activation of c-MET through hepatocyte growth factor (HGF) increases
      tumorigenesis, induces resistance, and is associated with poor prognosis in
      various solid tumors. However, the clinical value of serum HGF (sHGF) in patients
      with advanced non-small cell lung cancer (NSCLC), especially those receiving
      cytotoxic chemotherapy, remains unknown. Here, we show that sHGF may be useful to
      predict tumor response and progression-free survival (PFS) in patients with
      advanced NSCLC. A total of 81 patients with NSCLC were investigated. sHGF levels
      were evaluated using ELISA at 4 time-points: at pre-treatment, at response
      evaluation (1-2 months after treatment initiation), at the best tumor response,
      and at disease progression. As a control biomarker, CEA was also evaluated in
      lung adenocarcinoma. Positive-sHGF at response-evaluation predicted poor PFS
      compared with Negative-sHGF in both first-line (median, 153.5 vs. 288.0; P <
      0.05) and second-line treatment (87.0 vs. 219.5; P = 0.01). In 55 patients that
      received cytotoxic chemotherapy, multiple Cox proportional hazards models showed
      significant independent associations between poor PFS and Positive-sHGF at
      response-evaluation (hazard ratio, 4.24; 95% CI, 2.05 to 9.46; P < 0.01). Lung
      adenocarcinoma subgroup analysis showed that in patients receiving second
      cytotoxic chemotherapy, there were no significant differences in PFS between
      patients with low-CEA compared with those with high-CEA, but Positive-sHGF at pre
      treatment or at response-evaluation predicted poor PFS (35.0 vs. 132.0; P < 0.01,
      50.0 vs. 215.0; P < 0.01, respectively). These findings give a rationale for
      future research investigating the merit of sHGF as a potential clinical biomarker
      to evaluate HGF/c-MET activity, which would be useful to indicate administration
      of c-MET inhibitors.

PMID- 29069758
TI  - Transcriptional factor OCT4 promotes esophageal cancer metastasis by inducing
      epithelial-mesenchymal transition through VEGF-C/VEGFR-3 signaling pathway.
AB  - The octamer-binding transcription factor 4 (OCT4) can promote cancer
      proliferation and metastasis. Esophageal carcinoma (ECC) harbors different
      quantities of OCT4-positive cancer cells. These cells are highly malignant and
      prone to metastasis; however, the mechanism remains unknown. In this study, we
      found that OCT4 enhances vascular endothelial growth factor C (VEGF-C) promoter
      activity to promote VEGF-C expression and activates VEGF receptor 3 (VEGFR-3) in
      ECC cells, thereby inducing cancer cell epithelial-mesenchymal transition (EMT).
      Studies using xenograft models showed that OCT4 promoted xenograft growth and
      intraperitoneal implantation metastasis of ECC cells. Downregulation of OCT4
      expression could inhibit cancer metastasis. OCT4- and VEGF-C-positive ECC
      presented more malignant biological behaviors and the corresponding patients
      exhibited a poor prognosis. The study confirmed that the OCT4/VEGF-C/VEGFR-3/EMT
      signaling plays a role in the progression of ECC. Understanding of how OCT4
      regulates EMT and how ECC metastasis occurs will provide useful targets for the
      biological treatment of ECC.

PMID- 29069754
TI  - LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through
      down-regulating ABCB1 and ABCC1.
AB  - Long noncoding RNAs (LncRNAs) act as crucial regulators in various cancers
      including osteosarcoma (OS), yet their potential roles and molecular mechanisms
      in OS chemoresistance remain unclear. In the present study, we investigated the
      role and potential regulatory mechanism of the most down-regulated expressed
      lncRNA, FENDRR screened by our previous lncRNA microarray analysis between the
      paired doxorubicin-resistant and sensitive human osteosarcoma cell lines
      (MG63/DXR vs MG63). FENDRR expression was down-regulated in the doxorubicin
      resistant OS cell lines and tissues and negatively correlated to the poor
      prognosis of OS patients. Overexpression of FENDRR suppressed doxorubicin
      resistance, G2/M phase of cell cycle, and promoted cell apoptosis of osteosarcoma
      cells in vitro and tumor growth in vivo whereas FENDRR knockdown had the opposite
      effects. In addition, we found that FENDRR was mainly located in the cytoplasm
      and could regulate the drug resistance of osteosarcoma cells by negatively
      affecting posttranscriptional expression of ABCB1 and ABCC1. Together, our study
      demonstrated that lncRNA FENDRR may act as an inhibitory molecule of doxorubicin
      resistance through down-regulating the expression of ABCB1 and ABCC1 genes in
      osteosarcoma cells. These findings may extend the function of FENDRR in tumor
      progression and provide a novel target for reversing OS chemoresistance.

PMID- 29069760
TI  - Up-regulation of CIT promotes the growth of colon cancer cells.
AB  - Colon cancer is one of the major causes of cancer mortality worldwide. However,
      the underlying mechanism and therapeutic targets of colon cancer have not yet
      been fully elucidated. In the present study, we demonstrate that citron rho
      interacting, serine/threonine kinase 21 (CIT) promotes the growth of human colon
      cancer cells. CIT is overexpressed in human colon cancer tissues and cell lines.
      High expression of CIT predicts poor survival for patients with colon cancer. In
      colon cancer cells, CIT knockdown represses cellular proliferation and colony
      formation. Our in vivo xenograft experiments showed that CIT knockdown reduces
      the growth rate of colon cancer cells and the final tumor weight. We found that
      CIT knockdown induces cell cycle arrest and apoptosis in colon cancer cells.
      Further microarray and bioinformatics analyses indicated that CIT regulates the
      p53 signaling pathway, which may account for the effects of CIT on colon cancer
      cells. Taken together, our findings provide evidence that CIT may promote the
      development of colon cancer, at least in part, through the p53 signaling pathway.
      Therefore, CIT may be a potential therapeutic target for colon cancer treatment.

PMID- 29069757
TI  - Analysis of miRNA expression profile induced by short term starvation in breast
      cancer cells treated with doxorubicin.
AB  - Recent studies showed that dietary approaches restricting food intake can be
      helpful to hinder tumor progression. To date, the molecular mechanisms are
      unclear and a key role seems to be exerted by nutrient-related signaling
      pathways. Since several evidences showed that non-coding small RNAs, including
      microRNAs, are correlated to cancer progression and antiblastic treatment
      response, our work aims to study their involvement in a triple negative breast
      cancer (TNBC) cell line treated with doxorubicin under Short Term Starvation
      (STS) condition. Human TNBC cell line MDA-MB-231 and healthy breast cell line
      MCF10A were treated with 1 MUM doxorubicin for 24 h under STS condition for 48 h
      and miRNA expression profiles were analyzed using Taqman(r) Low Density Array A
      human microRNA microfluidic cards. In addition, the expression of specific mRNAs
      and miRNAs differentially expressed under STS was analyzed using Real-time PCR
      analyses. MiRNA expression profile analysis in MDA-MB-231 and MCF10A cells
      treated with doxorubicin under STS for 48 h could explain the molecular
      mechanisms underlying anticancer effects associated to STS. Among deregulated
      miRNAs, a subset, including miR-15b, miR-23a, miR-26a, miR-29a, miR-106b, miR
      128, miR-149, miR-181a, miR-192, miR-193b, miR-195, miR-324-3p and miR-494, has
      been shown to be involved in pathways related to drug sensitivity/resistance. The
      obtained data from our study suggest a potential involvement of some miRNAs in
      molecular pathways mediating the anticancer effects of STS in doxorubicin-treated
      breast cancer cells. Preliminary results seem to be encouraging and, in future,
      could allow the discovery of new potential targets useful for the development of
      new therapeutic approaches.

PMID- 29069752
TI  - The caudal pedunculopontine tegmental nucleus may be involved in the regulation
      of skeletal muscle activity by melanocortin-sympathetic pathway: a virally
      mediated trans-synaptic tracing study in spinally transected transgenic mice.
AB  - Understanding neuroanatomical sympathetic circuitry and neuronal connections from
      the caudal pedunculopontine tegmental nucleus to skeletal muscle is important to
      the study of possible mechanisms of pedunculopontine tegmental nucleus (PPTg) and
      cuneiform nucleus (CnF) that are involved in the regulation of skeletal muscle
      activity of the sympathetic pathway. The aim of this study was to use virus PRV
      614 to trace the melanocortin-sympathetic neural pathways from PPTg and CnF to a
      hindlimb muscle (gastrocnemius) in spinally transected MC4R-GFP transgenic mice.
      PRV-614 was injected into the gastrocnemius muscle after receiving a complete
      spinal cord transection below the L2 level. PRV-614/MC4R-GFP and PRV-614/TPH dual
      labeled neurons were found in the dissipated parts of PPTg (dpPPTg), but not
      between the compact parts of PPTg (cpPPTg) and CnF. It is proposed that a
      hierarchical pathway of neurons within the caudal pedunculopontine tegmental
      nucleus sends projections to the RVLM, which in turn projects onto the IML
      sympathetic preganglionic neurons that regulate muscle blood flow through
      melanocortin-sympathetic signals. Our results collectively indicate that MC4Rs
      expressed in caudal pedunculopontine tegmental nucleus may be involved in
      skeletal muscle activity of melanocortin-sympathetic pathways.

PMID- 29069759
TI  - Diagnosis of Pneumocystis jirovecii pneumonia with serum cell-free DNA in non-HIV
      infected immunocompromised patients.
AB  - Conventional respiratory tract specimens, such as bronchoalveolar lavage (BAL)
      fluid and induced sputum for diagnosing Pneumocystis jirovecii pneumonia (PCP) in
      immunocompromised patients are difficult to obtain. Besides, bronchoscopy is an
      invasive procedure that carries the risk of causing rapidly progressive
      respiratory insufficiency. By contrast, serum cell-free DNA (cfDNA) is easy to
      obtain and has been proven useful in diagnosing cancer, pregnancy associated
      complications, parasite infection and sepsis. In this study, we performed
      quantitative polymerase chain reaction (qPCR) to assess the diagnostic efficiency
      of using serum cfDNA, BAL fluid, and sputum DNA for PCP. Seventy-one patients (35
      PCP patients and 36 non-PCP patients) were enrolled according to the clinical PCP
      diagnostic criteria. The sensitivity, specificity, positive predictive value, and
      negative predictive value of PCR using serum cfDNA were 68.6% (95% CI, 50.7
      83.1), 97.2% (95% CI, 85.5-99.9), 96.0%, and 76.1%, respectively. PCR using BAL
      fluid and sputum had a high sensitivity (97.1% and 91.4%, respectively) but
      relatively low specificity (86.1% and 86.1%, respectively). The combination of
      the sputum PCR OR serum cfDNA PCR yielded a sensitivity of 97.1%.These results
      indicated that serum cfDNA might be a valuable method in PCP diagnosis.

PMID- 29069753
TI  - Loss of Barx1 promotes hepatocellular carcinoma metastasis through up-regulating
      MGAT5 and MMP9 expression and indicates poor prognosis.
AB  - Metastasis is the major dominant reason for poor prognosis of hepatocellular
      carcinoma (HCC) after surgical treatment. However, the molecular mechanism of
      metastasis has not been well characterzied. Here, we report a novel function of
      Barx homeobox1 (Barx1) in inhibiting HCC invasion and metastasis. Barx1
      expression is significantly decreased in human HCC tissues than in adjacent non
      tumorous tissues and normal liver tissues. Low Barx1 expression is correlated
      with higher tumor-nodule-metastasis stage and indicates poor prognosis. Down
      regulation of Barx1 promotes HCC migration, invasion and metastasis, whereas up
      regulation of Barx1 inhibits HCC migration, invasion and metastasis. Mannosyl
      (alpha-1,6-)-glycoprotein beta-1,6-N-acetyl-glucosaminyltransferase 5 (MGAT5) and
      matrix metallopeptidase 9 (MMP9) are direct target genes of Barx1. Knockdown of
      Barx1 up-regulates MGAT5 and MMP9 expression in HCC cells with low metastatic
      capability, whereas over-expression of Barx1 suppresses their expression in HCC
      cells with high metastatic capability. Knockdown of both MGAT5 and MMP9
      significantly decreases the invasion and metastasis abilities induced by Barx1
      knockdown. Barx1 expression is negatively correlated with MGAT5 and MMP9
      expression in human HCC tissues. Patients with low expression of Barx1 and high
      expression of MGAT5 or MMP9 are associated with poorer prognosis. Thus, loss of
      Barx1 represents a prognostic biomarker in human HCC patients.

PMID- 29069755
TI  - Identification of a novel YAP-14-3-3zeta negative feedback loop in gastric
      cancer.
AB  - Growing evidence indicates that 14-3-3zeta and yes-associated protein (YAP)
      substantially promote tumorigenesis and tumor development. However, the
      regulatory mechanism underlying these two proteins remains unknown. Herein, we
      report a new regulatory role of 14-3-3zeta in the phosphorylation of YAP and the
      feedback inhibition of 14-3-3zeta by YAP. YAP and 14-3-3zeta expression exhibited
      a negative correlation in gastric cancer (GC) tissues. Moreover, patients with
      higher YAP and lower 14-3-3zeta expression had poor prognoses. Studies have
      revealed that 14-3-3zeta promotes cytoplasmic retention and suppresses the
      transcriptional activity of YAP by inducing its phosphorylation. Furthermore, we
      observed that the overexpression of YAP significantly reduced the expression of
      14-3-3zeta by inducing its ubiquitination. YAP, 14-3-3zeta, and mouse double
      minute 2 homolog (MDM2) were colocalized, and the knockdown of MDM2 by siRNA
      attenuated the YAP-induced decrease of 14-3-3zeta. The binding of 14-3-3zeta and
      MDM2 was also restrained when the expression of YAP was interfered. Our results
      indicated the presence of a 14-3-3zeta-YAP negative regulatory feedback loop,
      which has a crucial role in cell proliferation and survival and is a potential
      target for the clinical treatment of GC.

PMID- 29069756
TI  - Endoplasmic reticulum chaperone prolyl 4-hydroxylase, beta polypeptide (P4HB)
      promotes malignant phenotypes in glioma via MAPK signaling.
AB  - Endoplasmic reticulum (ER) chaperone Prolyl 4-hydroxylase, beta polypeptide
      (P4HB) has previously been identified as a novel target for chemoresistance in
      glioblastoma multiforme (GBM). Yet its functional roles in glioma carcinogenesis
      remain elusive. In clinical analysis using human glioma specimens and Gene
      Expression Omnibus (GEO) profiles, we found that aberrant expression of P4HB was
      correlated with high-grade malignancy and an angiogenic phenotype in glioma.
      Furthermore, P4HB upregulation conferred malignant characteristics including
      proliferation, invasion, migration and angiogenesis in vitro, and increased tumor
      growth in vivo via the mitogen-activated protein kinase (MAPK) signaling pathway.
      Pathway analysis suggested genetic and pharmacologic inhibition of P4HB
      suppressed MAPK expression and its downstream targets were involved in
      angiogenesis and invasion. This is the first study that demonstrates the
      oncogenic roles of P4HB and its underlying mechanism in glioma. Since tumor
      invasion and Vascularisation are typical hallmarks in malignant glioma, our
      findings uncover a promising anti-glioma mechanism through P4HB-mediated
      retardation of MAPK signal transduction.

PMID- 29069761
TI  - Myeloid-specific genetic ablation of ATP-binding cassette transporter ABCA1 is
      protective against cancer.
AB  - Increased circulating levels of apolipoprotein A-I (apoA-I), the major protein of
      high-density lipoprotein (HDL), by genetic manipulation or infusion, protects
      against melanoma growth and metastasis. Herein, we explored potential roles in
      melanoma tumorigenesis for host scavenger receptor class B, type 1 (SR-B1), and
      ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), all mediators of
      apoA-I and HDL sterol and lipid transport function. In a syngeneic murine
      melanoma tumor model, B16F10, mice with global deletion of SR-B1 expression
      exhibited increased plasma HDL cholesterol (HDLc) levels and decreased tumor
      volume, indicating host SR-B1 does not directly contribute to HDL-associated anti
      tumor activity. In mice with myeloid-specific loss of ABCA1 (Abca1-M/-M ; A1-M/
      M), tumor growth was inhibited by ~4.8-fold relative to wild type (WT) animals.
      Abcg1-M/-M (G1-M/-M) animals were also protected by 2.5-fold relative to WT, with
      no further inhibition of tumor growth in Abca1/Abcg1 myeloid-specific double
      knockout animals (DKO). Analyses of tumor-infiltrating immune cells revealed a
      correlation between tumor protection and decreased presence of the immune
      suppressive myeloid-derived suppressor cell (MDSC) subsets, Ly-6G+Ly-6CLo and Ly
      6GnegLy-6CHi cells. The growth of the syngeneic MB49 murine bladder cancer cells
      was also inhibited in A1-M/-M mice. Collectively, our studies provide further
      evidence for an immune modulatory role for cholesterol homeostasis pathways in
      cancer.

PMID- 29069763
TI  - Macrophages are targets of retinoic acid signaling during the wound-healing
      process after thulium laser resection of the prostate.
AB  - BACKGROUND: The wound-healing process is very important for reducing
      complications after thulium laser resection of the prostate (TmLRP). The retinoic
      acid (RA) signaling pathway has been well studied in the wound-healing process of
      the skin and other organs. The goals of this study were to identify the role of
      RA signaling in the repair of the prostate after TmLRP and to investigate the
      molecular mechanism of this process. RESULTS: Retinoic acid receptors (RARs) were
      present in the prostate, and their expression was increased after TmLRP. RARbeta
      was expressed in the macrophages and may be related to the role of stromal cells
      in the wound-healing process. In vitro, RA enhanced the function of anti
      inflammatory macrophages and promoted stromal cell activation and angiogenesis.
      Arg1 was also increased via RARbeta after treatment with RA. MATERIALS AND
      METHODS: The expression of RARs was analyzed in vivo by immunohistochemistry
      (IHC), real time qPCR, and western blot analysis. THP-1 cells were co-treated
      with or without RA and stimulating factor and then assessed by ELISA and qPCR.
      The supernatants from these cells were cultured with stromal cells and vascular
      endothelial cells, and the effects on these cells were analyzed. CONCLUSIONS: We
      found that RA signaling was involved in the wound-healing process of the prostate
      after TmLRP. RA treated macrophages activated stromal cells and promoted
      angiogenesis. RARbeta was the key isoform in this process.

PMID- 29069773
TI  - Visualization and quantitation of epidermal growth factor receptor
      homodimerization and activation with a proximity ligation assay.
AB  - OBJECTIVES: Activation of the epidermal growth factor receptor (EGFR) results
      from receptor homodimerization and autophosphorylation and confers sensitivity to
      tyrosine kinase inhibitors in some tumors. However, the visual detection and
      quantitation of activated EGFR in the clinical setting has not been established.
      MATERIALS AND METHODS: A proximity ligation assay (PLA) was applied to detect
      EGFR homodimers in non-small cell lung cancer (NSCLC) cell lines and tissue
      specimens. RESULTS: PLA signals corresponding to EGFR homodimers were higher in
      NSCLC cell lines and tissue specimens positive for activating EGFR mutations than
      in those wild type (WT) for EGFR. Stimulation with EGF in NSCLC cells WT for EGFR
      or forced overexpression of EGFR in Ba/F3 cells resulted in marked EGFR
      homodimerization. The extent of EGFR homodimerization appeared related to that of
      EGFR autophosphorylation in NSCLC cells WT for EGFR. CONCLUSION: PLA may provide
      a new tool for detection and quantitation of EGFR homodimers in NSCLC and other
      tumors.

PMID- 29069771
TI  - Expression of protein kinase C gamma promotes cell migration in colon cancer.
AB  - Despite extensive efforts, Protein Kinase Cs (PKCs) have proven to be an
      intractable target in cancer therapies. Traditionally it was accepted that PKCs
      act as tumour promoters, however new research suggests that PKCs may play an
      important role in the suppression of cancer. A challenge in targeting PKCs is the
      limited data available in patient samples. One of the PKC isozymes, PKC gamma, is
      thought to be present only in the brain and has been largely neglected in the
      context of cancer. Analysis of gene expression levels of PKC gamma in patient
      matched normal and colon cancer tissue samples revealed an up-regulation of the
      gene in the cancer tissue of 54% of the patients examined. Mechanistically we
      demonstrate that a reduction in the levels of PKC gamma in the colon cancer cells
      inhibits cell migration and foci formation. Further to this, we observe an
      increase in cell adhesion and proliferation following the reduction of PKC gamma
      levels in the cell. Thus, PKC gamma plays a key role in colon cancer; making it
      an important isozyme that needs to be reconsidered in the context of cancer
      therapies.

PMID- 29069764
TI  - Dual effects of constitutively active androgen receptor and full-length androgen
      receptor for N-cadherin regulation in prostate cancer.
AB  - Constitutively active androgen receptor (AR) variants have been involved in the
      expression of mesenchymal markers such as N-cadherin in prostate cancer (PCa).
      However, the underlying molecular mechanisms remain elusive. It remains unclear,
      whether N-cadherin gene (CDH2) is a direct transcriptional target of AR variants
      or whether the observed upregulation is due to indirect effects through
      additional regulatory factors. Moreover, the specific contribution of full-length
      AR and AR variants in N-cadherin regulation in PCa has never been explored
      deeply. To investigate this, we artificially mimicked the co-expression of AR
      variants together with a full-length AR and performed miRNA-seq, RNA-seq and ChIP
      assays. Our results were in favor of a direct AR variants action on CDH2. Our
      data also revealed a distinctive mode of action between full-length AR and AR
      variants to regulate N-cadherin expression. Both wild type AR and AR variants
      could interact with a regulatory element in intron 1 of CDH2. However, a higher
      histone H4 acetylation in this genomic region was only observed with AR variants.
      This suggests that full-length AR may play an occluding function to impede CDH2
      upregulation. Our data further highlighted a negative effect of AR variants on
      the expression of the endogenous full-length AR in LNCaP. These differences in
      the mode of action of AR variants and full-length AR for the control of one key
      gene for prostate cancer progression could be worth considering for targeting AR
      variants in PCa.

PMID- 29069762
TI  - Cell lines generated from a chronic lymphocytic leukemia mouse model exhibit
      constitutive Btk and Akt signaling.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature
      CD5+ B cells in blood. Spontaneous apoptosis of CLL cells in vitro has hampered
      in-depth investigation of CLL pathogenesis. Here we describe the generation of
      three monoclonal mouse cell lines, EMC2, EMC4 and EMC6, from the IgH.TEMU CLL
      mouse model based on sporadic expression of SV40 large T antigen. The cell lines
      exhibit a stable CD5+CD43+IgM+CD19+ CLL phenotype in culture and can be
      adoptively transferred into Rag1-/- mice. RNA-seq analysis revealed only minor
      differences between the cell lines and their primary tumors and suggested that NF
      kappaB and mTOR signaling pathways were involved in cell line outgrowth. In vitro
      survival and proliferation was dependent on constitutive phosphorylation of
      Bruton's tyrosine kinase (Btk) at Y551/Y223, and Akt(S473). Treatment of the cell
      lines with small molecule inhibitors specific for Btk (ibrutinib) or PI3K
      (idelalisib), which is upstream of Akt, resulted in reduced viability,
      proliferation and fibronectin-dependent cell adhesion. Treatment of cell line
      engrafted Rag1-/- mice with ibrutinib was associated with transient
      lymphocytosis, reduced splenomegaly and increased overall survival. Thus, by
      generating stable cell lines we established a novel platform for in vitro and in
      vivo investigation of CLL signal transduction and treatment modalities.

PMID- 29069775
TI  - Drug repositioning of mevalonate pathway inhibitors as antitumor agents for
      ovarian cancer.
AB  - Drug repositioning is an alternative strategy redirecting existing drugs for new
      disease. We have previously reported an antitumor effect of statins,
      antidyslipidemic drugs, on ovarian cancer in vitro and in vivo. In this study, we
      investigated the antitumor effects of other mevalonate pathway inhibitors and the
      mechanism of the antitumor effect from a metabolic perspective. The effects of
      inhibitors of the mevalonate pathway on tumor cell growth were evaluated in
      vitro. Bisphosphonates that inhibit this pathway are commonly used as
      antiosteoporotic drugs, and antitumor effects of the bisphosphonate were examined
      in vitro and in vivo. Metabolites in SKOV3 ovarian cancer cells were analyzed
      before and after lovastatin treatment, using capillary electrophoresis-mass
      spectrometry. All mevalonate pathway inhibitors showed concentration-dependent
      inhibitory effects on tumor cell growth. Particularly marked effects were
      obtained with inhibitors of farnesyltransferase and geranylgeranyltransferase.
      The bisphosphonate was also shown to have an antitumor effect in vivo. The
      expression of autophagy marker LC3A/3B was increased in cells after treatment. In
      metabolomics analysis, lovastatin treatment increased the metabolites involved in
      the tricarboxylic acid cycle while reducing the metabolites associated with
      glycolysis. Also it decreased glutathione and resulted to work with
      chemotherapeutic agents synergistically. Inhibition at any point in the
      mevalonate pathway, and especially of farnesyl pyrophosphate and geranylgeranyl
      pyrophosphate, suppresses growth of ovarian cancer cells. Inhibition of this
      pathway may induce autophagy, cause a shift to activation of the tricarboxylic
      acid cycle and enhance susceptibility to chemotherapy. Drug repositioning
      targeting mevalonate pathway for ovarian cancer deserves consideration for
      clinical application.

PMID- 29069765
TI  - MARCKS promotes invasion and is associated with biochemical recurrence in
      prostate cancer.
AB  - BACKGROUND: Overtreatment of low-grade prostate cancer is a recognised problem
      for clinicians and patients. However, under-treatment runs the risk of missing
      the opportunity for cure in those who could benefit. Identification of new
      biomarkers of disease progression, including metastases, is required to better
      stratify and appropriately treat these patients. The ability to predict if
      prostate cancer will recur is an important clinical question that would impact
      treatment options for patients. Studies in other cancers have associated MARCKS
      with metastasis. METHODS: Tissue microarrays of local prostatectomy samples from
      a cohort of biochemical recurrent and non-biochemical recurrent tumours were
      assayed for MARCKS protein expression. Prostate cancer cell lines were
      transfected with siRNA targeting MARCKS or a control and functional endpoints of
      migration, invasion, proliferation, viability and apoptosis were measured. Actin
      was visualised by fluorescent microscopy and evidence of a cadherin switch and
      activation of the AKT pathway were assayed. RESULTS: MARCKS was upregulated in
      biochemical recurrent patients compared to non-biochemical recurrent. Knockdown
      of MARCKS reduced migration and invasion of prostate cancer cells, reduced MMP9
      mRNA expression, as well as decreasing cell spreading and increased cell:cell
      adhesion in prostate cancer cell colonies. Knockdown of MARCKS had no effect on
      proliferation, viability or apoptosis of the prostate cancer cells. CONCLUSIONS:
      In conclusion, MARCKS promotes migration and invasion and is associated with
      biochemical recurrence in localised prostate cancer tumours. The mechanisms by
      which this occurs have yet to be fully elucidated but lack of a cadherin switch
      indicates it is not via epithelial-to-mesenchymal transition. Actin rearrangement
      indicates that MARCKS promotes invasion through regulating the architecture of
      the cell.

PMID- 29069767
TI  - Clinical study on the relationship between hepatitis B virus infection and risk
      of breast cancer: a large sized case-control and single center study in southwest
      of China.
AB  - PURPOSE: Chronic hepatitis C virus (HCV) infection is reported to be associated
      with early-onset breast cancer, while, as a hepadnavirus, hepatitis B virus(HBV)
      infection is more common than HCV in China. In this article, it is aimed to study
      the relationship between HBV infection and risk of breast cancer in China.
      METHODS: The clinical data of 2452 cases of initially diagnosed breast cancer and
      1926 cases of benign breast disease (as controls) with the consecutive reports of
      HBV serological markers and liver function tests, available in the Electronic
      Medical Records of the Breast Cancer Center of Chongqing, the southwest of China,
      from January 2011 to March 2015, were collected for analysis. RESULTS: The
      average age of the initially diagnosed breast cancer patients was 50.3+/-11.3
      years with the age peaking about 40- 49yeaers (39.7%). The positive rate (8.2%)
      of hepatitis B surface antigen in breast cancer patients was relatively higher
      than that (7.8%) in controls (P>0.05). While, the positive rate (66.4%)of
      hepatitis B core antibody in breast cancer patients was significantly higher than
      that (53.7%) in controls (P<0.05), so were the similar results in the age groups
      of 40-49 years, after multiple layer analysis stratified by age and compare HBV
      markers adjusting age with binary logistic regression. Meanwhile, the status of
      albumin, aminotransferase and aspartate transaminase (41.4 g/L, 22.9 U/L, 22.0
      U/L) in breast cancer patients were significantly poorer than those (44.1
      g/L,16.8 U/L, 19.2 U/L) in controls (P<0.05). CONCLUSIONS: Exposure to HBV
      infection may be a risk factor for breast cancer and may be also related to the
      earlier age onset of breast cancer (peaked around 40-49 years) among Chinese
      females.

PMID- 29069770
TI  - Genome-wide functional analysis on the molecular mechanism of specifically
      biosynthesized fluorescence Eu complex.
AB  - Fluorescence imaging as an attractive diagnostic technique is widely employed for
      early diagnosis of cancer. Self-biosynthesized fluorescent Eu complex in situ in
      Hela cells have realized specifically and accurately fluorescence imaging for
      cancer cells. But the molecular mechanism of the in situ biosynthesized process
      is still unclear. In order to reveal this mechanism, we have investigated whole
      genome expression profiles with cDNA microarray, incubated with Eu solution in
      Hela cells for 24 h. Methylthiazoltetrazolium (MTT) assay and laser confocal
      fluorescence microscopy study showed the low cytotoxicity and specifically
      fluorescence imaging of Eu complex in Hela cells. It is observed that 563 up
      regulated genes and 274 down-regulated genes were differentially expressed.
      Meanwhile, quantitative RT-PCR was utilized to measure the expression of some
      important genes, which validated the results of microarray data analysis.
      Besides, GO analysis showed that a wide range of differential expression
      functional genes involved in three groups, including cellular component,
      molecular function and cellular biological process. It was evident that some
      important biological pathways were apparently affected through KEGG pathway
      analysis, including focal adhesion pathway and PI3K (phosphatidylinositol 3' 
      kinase)-Akt signaling pathway, which can influence glycolytic metabolism and
      NAD(P)H-oxidases metabolic pathway.

PMID- 29069766
TI  - Prognostic significance of clinicopathological factors in early breast cancer: 20
      years of follow-up in a single-center analysis.
AB  - BACKGROUND: To quantify the effect of traditional prognostic factors [nodal
      status, estrogen-receptor (ER), progesterone-receptor (PR), human epidermal
      growth factor receptor 2 (HER2)] on long-term outcome of patients with early
      breast cancer (EBC), treated in clinical practice over a period of about twenty
      years. RESULTS: 1198 consecutive patients were identified. Median DFS (disease
      free survival): ER+/PR+/-/HER2-, 165 months (mo) if node-negative (N0) and 114mo
      if node-positive (N+) (p < 0.001); triple-negative (TN), 109mo if N0 and 65mo if
      N+ (p 0.144); ER+/PR+/-/HER2+ in patients not-treated with adjuvant trastuzumab
      (T-), not reached if N0 and 114mo if N+ (p 0.297); ER+/PR+/-/HER2+ in patients
      treated with trastuzumab (T+), 95mo if N0 and 85mo if N+ (p 0.615); ER-/PR-/HER2+
      T-, not reached if N0 and 26mo if N+ (p 0.279); ER-/PR-/HER2+ T+, not reached if
      N0 and 66mo if N+ (p 0.014). Median OS (overall survival): ER+/ PR+/-/HER2-,
      166mo if N0 and 144mo if N+ (p 0.028); TN, 158mo if N0 and 96mo if N+ (p 0.384);
      ER+/PR+/-/HER2+ T-, not reached if N0 and 157mo if N+ (p 0.475), ER+/PR+/-/HER2+
      T+, not reached if N0 and 106mo if N+ (p 0.436); ER-/PR-/HER2+ T-, not reached if
      N0 and 34mo if N+ (p 0.273); ER-/PR-/HER2+ T+, not reached neither if N0 nor if
      N+ (p 0.094). MATERIALS AND METHODS: Disease-free survival (DFS) and overall
      survival (OS) were evaluated according to tumor characteristics, based on
      information retrospectively retrieved from patients' medical records.
      CONCLUSIONS: Pathological tumor characteristics and nodal status still represent
      useful tools in treatment selection and follow-up decision making of EBC patients
      in clinical practice.

PMID- 29069772
TI  - The integrative clinical impact of tumor-infiltrating T lymphocytes and NK cells
      in relation to B lymphocyte and plasma cell density in esophageal and gastric
      adenocarcinoma.
AB  - BACKGROUND: Several studies have demonstrated a prognostic impact of tumor
      infiltrating T lymphocytes and natural killer (NK) cells in esophageal and
      gastric adenocarcinoma, but whether these associations differ by the density of
      tumor-infiltrating immune cells of the B cell lineage remains largely unknown.
      RESULTS: High infiltration of any T and NK lymphocytes investigated was in
      general associated with a favorable prognosis, but the strongest beneficial
      prognostic impact was seen in combination with high B lymphocyte infiltration.
      These findings were most evident in gastric cancer, where significant
      interactions in relation to OS were observed for CD3+, CD8+ and FoxP3+ with CD20+
      cells (pinteraction =0.012, 0.009 and 0.007, respectively) and for FoxP3+ with
      IGKC+ cells (pinteraction =0.034). In esophageal tumors, there was only a
      significant interaction for CD3+ and CD20 + cells (pinteraction =0.028). METHODS:
      Immunohistochemistry and automated image analysis was applied to assess the
      density of T lymphocytes (CD3+, CD8+, FoxP3+) and NK cells (NKp46+) in
      chemoradiotherapy-naive tumors from a consecutive cohort of 174 patients with
      resected esophageal or gastric adenocarcinoma. The density of B lymphocytes
      (CD20+) and plasma cells (IGKC+) had been assessed previously. Kaplan-Meier
      analysis and Cox proportional hazard's modelling was applied to examine the
      impact of the investigated markers on time to recurrence (TTR) and overall
      survival (OS). CONCLUSIONS: These data support that the antitumoral effects of
      tumor-infiltrating T lymphocytes in esophageal and gastric adenocarcinoma may be
      largely dependent on a functional interplay between T and B lymphocytes or plasma
      cells.

PMID- 29069776
TI  - The crucial role of SRPK1 in IGF-1-induced EMT of human gastric cancer.
AB  - In recent years, the insulin-like growth factor (IGF-1) and serine-arginine
      protein kinase 1 (SRPK1) have been reported to be implicated in the pithelial
      mesenchymal transition (EMT) in many kinds of malignancies. However, the
      potential roles of IGF-1-SRPK1 signaling in the EMT of gastric cancer (GC) have
      not been investigated. In the present study, the in-vitro assays were used to
      investigate the molecular role of SRPK1 in cell cycle, motility and invasiveness.
      We demonstrated that the expressions of SRPK1 or insulin-like growth factor
      receptor 1 (IGF1R) were significantly increased in GC tissues and cells than
      those in normal tissues and GES-1 cells, and closely associated with metastasis,
      stage and prognosis. Western blot analysis showed that IGF-1 treatment can induce
      the expression of p-AKT and EMT biomarkers (N-cadherin, MMP2 and Slug) in a dose
      dependent fashion in MGC803 and BGC823 cells. On the other hand, the knockdown of
      SRPK1 attenuated IGF-1-induced increase of EMT biomarkers and p-AKT. Besides, in
      vitro analysis showed that knockdown of SRPK1 induced cell cycle arrest in G0/G1
      phase, and affected cell migration and invasion. In conclusion, IGF-1-IGF1R
      pathway induced the expression of SRPK1 to control the progression of EMT via AKT
      pathway in the development of GC. Our findings lay a promising foundation for the
      IGF-1-IGF1R axis-targeting therapy in GC patients.

PMID- 29069774
TI  - Targeting of PHOX2B expression allows the identification of drugs effective in
      counteracting neuroblastoma cell growth.
AB  - The pathogenic role of the PHOX2B gene in neuroblastoma is indicated by
      heterozygous mutations in neuroblastoma patients and by gene overexpression in
      both neuroblastoma cell lines and tumor samples. PHOX2B encodes a transcription
      factor which is crucial for the correct development and differentiation of
      sympathetic neurons. PHOX2B overexpression is considered a prognostic marker for
      neuroblastoma and it is also used by clinicians to monitor minimal residual
      disease. Furthermore, it has been observed that neuronal differentiation in
      neuroblastoma is dependent on down-regulation of PHOX2B expression, which
      confirms that PHOX2B expression may be considered a target in neuroblastoma.
      Here, PHOX2B promoter or 3' untranslated region were used as molecular targets in
      an in vitro high-throughput approach that led to the identification of molecules
      able to decrease PHOX2B expression at transcriptional and likely even at post
      transcriptional levels. Further functional investigations carried out on PHOX2B
      mRNA levels and biological consequences, such as neuroblastoma cell apoptosis and
      growth, showed that chloroquine and mycophenolate mofetil are most promising
      agents for neuroblastoma therapy based on down-regulation of PHOX2B expression.
      Finally, a strong correlation between the effect of drugs in terms of down
      regulation of PHOX2B expression and of biological consequences in neuroblastoma
      cells confirms the role of PHOX2B as a potential molecular target in
      neuroblastoma.

PMID- 29069769
TI  - Xuefu zhuyu decoction improves cognitive impairment in experimental traumatic
      brain injury via synaptic regulation.
AB  - An overarching consequence of traumatic brain injury (TBI) is the cognitive
      impairment. It may hinder individual performance of daily tasks and determine
      people's subjective well-being. The damage to synaptic plasticity, one of the key
      mechanisms of cognitive dysfunction, becomes the potential therapeutic strategy
      of TBI. In this study, we aimed to investigate whether Xuefu Zhuyu Decoction
      (XFZYD), a traditional Chinese medicine, provided a synaptic regulation to
      improve cognitive disorder following TBI. Morris water maze and modified
      neurological severity scores were performed to assess the neurological and
      cognitive abilities. The PubChem Compound IDs of the major compounds of XFZYD
      were submitted into BATMAN-TCM, an online bioinformatics analysis tool, to
      predict the druggable targets related to synaptic function. Furthermore, we
      validated the prediction through immunohistochemical, RT-PCR and western blot
      analyses. We found that XFZYD enhanced neuroprotection, simultaneously improved
      learning and memory performances in controlled cortical impact rats.
      Bioinformatics analysis revealed that the improvements of XFZYD implied the Long
      term potentiation relative proteins including NMDAR1, CaMKII and GAP-43. The
      further confirmation of molecular biological studies confirmed that XFZYD
      upregulated the mRNA and protein levels of NMDAR1, CaMKII and GAP-43.
      Pharmacological synaptic regulation of XFZYD could provide a novel therapeutic
      strategy for cognitive impairment following TBI.

PMID- 29069768
TI  - Direct comparison study of DNA methylation markers in EpCAM-positive circulating
      tumour cells, corresponding circulating tumour DNA, and paired primary tumours in
      breast cancer.
AB  - Circulating Tumour Cells (CTCs) and circulating tumour DNA (ctDNA) represent a
      non-invasive liquid biopsy approach for the follow-up and therapy management of
      cancer patients. We evaluated whether DNA methylation status in CTCs and ctDNA is
      comparable and whether it reflects the status of primary tumours. We compared the
      methylation status of three genes, SOX17, CST6 and BRMS1 in primary tumours,
      corresponding CTCs and ctDNA in 153 breast cancer patients and healthy
      individuals, by using real time methylation specific PCR. We report a clear
      association between the EpCAM-positive CTC-fraction and ctDNA for SOX17 promoter
      methylation both for patients with early (P = 0.001) and metastatic breast cancer
      (P = 0.046) but not for CST6 and BRMS1. In early breast cancer, SOX17 promoter
      methylation in the EpCAM-positive CTC-fraction was associated with CK-19 mRNA
      expression (P = 0.006) and worse overall survival (OS) (P = 0.044). In the
      metastatic setting SOX17 promoter methylation in ctDNA was highly correlated with
      CK-19 (P = 0.04) and worse OS (Rho = 0.016). SOX17 methylation status in CTCs and
      ctDNA was comparable and was associated with CK-19 expression but was not
      reflecting the status of primary tumours in breast cancer. DNA methylation
      analysis of SOX17 in CTCs and matched ctDNA provides significant prognostic
      value.

PMID- 29069777
TI  - Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1
      induced exhaustion of T-cells.
AB  - Antibodies targeting the PD-1/PD-L1 immune checkpoint achieved spectacular
      success in anticancer therapy in the recent years. In contrast, no small
      molecules with cellular activity have been reported so far. Here we provide
      evidence that small molecules are capable of alleviating the PD-1/PD-L1 immune
      checkpoint-mediated exhaustion of Jurkat T-lymphocytes. The two optimized small
      molecule inhibitors of the PD-1/PD-L1 interaction, BMS-1001 and BMS-1166,
      developed by Bristol-Myers Squibb, bind to human PD-L1 and block its interaction
      with PD-1, when tested on isolated proteins. The compounds present low toxicity
      towards tested cell lines and block the interaction of soluble PD-L1 with the
      cell surface-expressed PD-1. As a result, BMS-1001 and BMS-1166 alleviate the
      inhibitory effect of the soluble PD-L1 on the T-cell receptor-mediated activation
      of T-lymphocytes. Moreover, the compounds were effective in attenuating the
      inhibitory effect of the cell surface-associated PD-L1. We also determined the X
      ray structures of the complexes of BMS-1001 and BMS-1166 with PD-L1, which
      revealed features that may be responsible for increased potency of the compounds
      compared to their predecessors. Further development may lead to the design of an
      anticancer therapy based on the orally delivered immune checkpoint inhibition.

PMID- 29069779
TI  - MMP16 promotes tumor metastasis and indicates poor prognosis in hepatocellular
      carcinoma.
AB  - Matrix metalloproteinase (MMPs) participates in multiple biological behaviors and
      plays an important role in regulating tumor invasion. However, the functions of
      MMP16 in hepatocellular carcinoma (HCC) remains unknown. The prognostic value of
      MMP16 was studied in TCGA database and validation cohort. MMP16-silencing HCC
      cells (HepG2 and HCCLM3) were used for evaluating cell proliferation and invasion
      by CCK-8 and Transwell assays. Our results showed that the MMP16 was a predictor
      for overall survival in patients with HCC (HR: 1.169, 95% CI: 1.034-1.321, P =
      0.013) in TCGA database. In validation cohort, MMP16 expression was an
      independent predictor for survival in both univariate and multivariate analysis
      (P < 0.05). Furthermore, knockdown MMP16 weakened the cell invasive potential by
      inhibiting epithelial-mesenchymal transition (EMT) process. Therefore, our
      findings showed that MMP16 was a prognostic factor in HCC, ectopic MMP16
      expression promoted invasion of HCC cells by inducing EMT process, suggesting a
      tumor oncogenic function in HCC and provides the potential therapeutic target for
      the treatment of HCC.

PMID- 29069778
TI  - Discovery and validation of the tumor-suppressive function of long noncoding RNA
      PANDA in human diffuse large B-cell lymphoma through the inactivation of MAPK/ERK
      signaling pathway.
AB  - Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer
      related mortality, and responds badly to existing treatment. Thus, it is of
      urgent need to identify novel prognostic markers and therapeutic targets of
      DLBCL. Recent studies have shown that long non-coding RNAs (lncRNAs) play an
      important role in the development of cancer. By using the next generation HiSeq
      sequencing assay, we determined lncRNAs exhibiting differential expression
      between DLBCL patients and healthy controls. Then, RT-qPCR was performed for
      identification in clinical samples and cell materials, and lncRNA PANDA was
      verified to be down-regulated in DLBCL patients and have considerable diagnostic
      potential. In addition, decreased serum PANDA level was correlated to poorer
      clinical outcome and lower overall survival in DLBCL patients. Subsequently, we
      determined the experimental role of lncRNA PANDA in DLBCL progression. Luciferase
      reporter assay and chromatin immunoprecipitation assay suggested that lncRNA
      PANDA was induced by p53 and p53 interacts with the promoter region of PANDA.
      Cell functional assay further indicated that PANDA functioned as a tumor
      suppressor gene through the suppression of cell growth by a G0/G1 cell cycle
      arrest in DLBCL. More importantly, Cignal Signal Transduction Reporter Array and
      western blot assay showed that lncRNA PANDA inactivated the MAPK/ERK signaling
      pathway. In conclusion, our integrated approach demonstrates that PANDA in DLBCL
      confers a tumor suppressive function through inhibiting cell proliferation and
      silencing MAPK/ERK signaling pathway. Thus, PANDA may be a promising therapeutic
      target for patients with DLBCL.

PMID- 29069781
TI  - Downregulation of circulating exosomal miR-638 predicts poor prognosis in colon
      cancer patients.
AB  - Exosome-encapsulated microRNAs have been recognized as novel and stable
      biomarkers for cancer. However, little is known about the role of exosomal
      microRNAs in colon cancer. In the present study, we investigated the expression
      of serous exosomal microRNA-638 (miR-638) and its prognostic effect in patients
      with colon cancer. Serous exosomal samples were assayed by quantitative real-time
      PCR. Kaplan-Meier analysis was adopted to determine the overall survival (OS) and
      disease-free survival (DFS) of colon cancer patients. Cox regression analysis was
      applied to assess the potential association between serous exosomal miR-638 and
      clinicopathological factors of colon cancer patients. MiR-638 was significantly
      reduced in serum exosomes of colon cancer patients compared with healthy
      controls. Decreased level of serous exosomal miR-638 was more significant in
      colon cancer patients at later TNM stage or with liver metastasis. Kaplan-Meier
      analysis showed that colon cancer patients with reduced level of serous exosomal
      miR-638 had poor OS and DFS. In addition, the Cox regression analysis suggested
      serous exosomal miR-638 was a prognostic factor for colon cancer independent of
      TNM stage and liver metastasis. In conclusion, serous exosomal miR-638 is a
      useful biomarker for the prediction of colon cancer prognosis.

PMID- 29069782
TI  - Common genetic variant rs3802842 in 11q23 contributes to colorectal cancer risk
      in Chinese population.
AB  - A genome-wide association study identified a common genetic variant rs3802842 at
      11q23 to be associated with CRC risk with OR=1.1 and P = 5.80E-10 in European
      population. In Chinese population, several genetic association studies have
      investigated the association between rs3802842 variant and CRC risk. However
      these studies reported both positive and negative association results. It is
      still necessary to evaluate a specific variant in a specific population, which
      would be informative to reveal the disease mechanism. Until recently, there is no
      a systemic study to evaluate the potential association between rs3802842 and CRC
      risk in Chinese population by a meta-analysis method. Here, we aim to evaluate
      this association in Chinese population by a meta-analysis method using 12077
      samples including 5816 CRC cases and 6261 controls. We identified the T allele of
      rs3802842 to be significantly related with an increase CRC risk (P=2.22E-05,
      OR=1.14, 95% CI 1.07-1.21) in Chinese population.

PMID- 29069783
TI  - TLE1 inhibits anoikis and promotes tumorigenicity in human lung cancer cells
      through ZEB1-mediated E-cadherin repression.
AB  - The Transducin-like enhancer of split 1 (TLE1) corepressor protein is
      overexpressed in human lung tumors and is a putative lung-specific oncogene.
      However, the molecular mechanism underlying its oncogenic function remains to be
      delineated. Here, we report an important role of TLE1 in promoting lung
      tumorigenesis by a mechanism involving induction of anoikis resistance. Using the
      human lung adenocarcinoma A549 and immortalized bronchial epithelial BEAS-2B cell
      lines, we observed that TLE1 inhibits anoikis through transcriptional repression
      of E-cadherin gene. In support of E-cadherin as a downstream target of TLE1 to
      block anoikis, forced expression of E-cadherin attenuated TLE1-induced anoikis
      resistance while E-cadherin downregulation decreased the anoikis sensitivity of
      TLE1 knockdown cells. Furthermore, we determined that E-cadherin expression is
      transcriptionally induced upon loss of cell attachment and functions as an
      effector of anoikis. Loss of E-cadherin via the siRNA strategy or exogenous TLE1
      expression was sufficient to attenuate anoikis in A549 and BEAS-2B cells.
      Importantly, we demonstrated that the ZEB1 transcriptional factor is required for
      TLE1-mediated E-cadherin repression and anoikis resistance. ZEB1 interacted with
      and recruited the TLE1 to the E-cadherin promoter to impose histone deacetylation
      and gene silencing. In vivo, TLE1 strongly promoted tumorigenicity of A549 cells
      in a ZEB1-dependent manner. Underscoring its role in anoikis insensitivity of
      lung cancer cells, the TLE1-mediated E-cadherin repression was negatively
      regulated by the tumor suppressor Bcl-2 inhibitor of transcription 1 (Bit1) to
      effect anoikis. These findings identify the ZEB1/TLE1/E-cadherin transcriptional
      mechanism as a novel pathway that promotes anoikis resistance and oncogenicity of
      lung cancer cells.

PMID- 29069784
TI  - High expression of dedicator of cytokinesis 1 (DOCK1) confers poor prognosis in
      acute myeloid leukemia.
AB  - DOCK family genes encode evolutionarily conserved guanine nucleotide exchange
      factors for Rho GTPase involving multiple biological functions. Yet the patterns
      and prognostic significance of their expression in acute myeloid leukemia (AML)
      remain unexplored. Here we analyzed the expression patterns of 11 DOCK family
      genes in AML cells based on the array data of 347 patients from our cohort and
      several other published datasets. We further focused on the implications of the
      expression of DOCK1 since it was the only one in DOCK family to be associated
      with survival. Physiological functions and biological pathways associated with
      DOCK1 were identified using bioinformatics approaches. With a median follow up of
      57 months, higher DOCK1 expression was associated with shorter disease free and
      overall survival. The finding could be validated by two independent cohorts.
      Multivariate analysis showed higher DOCK1 expression as a strong independent
      unfavorable prognostic factor. Higher DOCK1 expression was closely associated
      with older age, higher platelet and peripheral blast counts, intermediate-risk
      cytogenetics, FLT3-ITD, MLL-PTD and mutations in PTPN11, NPM1, RUNX1, ASXL1 and
      DNMT3A. Functional enrichment analysis suggested the association of DOCK1
      overexpression with several key physiological pathways including cell
      proliferation, motility, and chemotaxis. Therefore, we suggested that AML with
      higher DOCK1 expression showed characteristic clinical and biological features.
      DOCK1 expression is an important prognostic marker and a potential therapeutic
      target for the treatment of AML. Studies in large prospective cohorts are
      necessary to confirm our findings. Further mechanistic studies to delineate the
      role of DOCK1 in the leukemogenesis are warranted.

PMID- 29069789
TI  - Postoperative course and prognostic value of circulating angiogenic cytokines
      after pancreatic cancer resection.
AB  - BACKGROUND: Circulating angiogenic cytokines (CACs) have been confirmed as
      prognostic biomarkers and therapeutic targets in several solid tumors. However,
      their role as prognostic biomarkers in resected pancreatic ductal adenocarcinoma
      (PDAC) is unknown. RESULTS: The expression of CACs in patients with PDAC differs
      from those with CP both pre- and postoperatively. Correlation analyses show
      significant correlations between circulating levels of CACs: VEGF was correlated
      with IL-6 (r = 0.457), FGF (r = 0.44), G-CSF (r = 0.543), HGF (r = 0.586) and SDF
      1alpha (r = 0.784) before the surgery. The circulating levels of TNF-alpha
      correlated with the serum concentration of IL-4 before (r= 0.656) and after the
      resection (r = 0.776 on POD 3, r = 0.865 on POD 7). Gender did not show any
      correlation with serum levels of CAC, except for significantly higher levels of
      EGF in males (P = 0.002). Other clinicopathological variables such as age (< 65
      vs. > 65 years), T, N, or UICC stage did not have an association with the
      cytokine levels. The multivariate model including the entire angiogenic panel
      revealed that postoperative increasing levels of EGF (P = 0.023), PDGFA-A (P =
      0.024), TNF-alpha (P = 0.001) and IL-8 (P = 0.049) were associated with a
      favorable prognosis, whereas elevating levels of VEGF (P = 0.005) correlated with
      a poor cancer-specific survival. MATERIALS AND METHODS: Preoperative and
      postoperative blood samples were collected in patients undergoing surgery for
      PDAC (n = 40) or chronic pancreatitis (CP; n = 9). Serum levels of 13 angiogenic
      cytokines (IL-4, IL-6, FGF-b, G-CSF, TNF-alpha, VEGF, HGF, SDF-1alpha, IL-8, EGF,
      Ang-1, PDGF-AA and PlGF) were analyzed using ELISA and Multiplex. Prognostic
      factors were identified by a Cox proportional hazards model. CONCLUSIONS:
      Postoperative changes of serum levels of certain angiogenic cytokines correlate
      with patients' prognosis after resection for pancreatic cancer. CACs should thus
      be considered as biomarkers in patients with resected pancreatic cancer.

PMID- 29069780
TI  - Induction of GD3/alpha1-adrenergic receptor/transglutaminase 2-mediated erythroid
      differentiation in chronic myelogenous leukemic K562 cells.
AB  - The disialic acid-containing glycosphingolipid GD3 recruited membrane
      transglutaminase 2 (TG2) as a signaling molecule for erythroid differentiation in
      human chronic myelogenous leukemia (CML) K562 cells. The alpha1-adrenergic
      receptor (alpha1-AR)/TG2-mediated signaling pathway regulated GD3 functions,
      including gene expression and production, to differentiate CML K562 cells into
      erythroid lineage cells. Epinephrine, an AR agonist, increased membrane
      recruitment as well as GTP-photoaffinity of TG2, inducing GD3 synthase gene
      expression. Epinephrine activated PI3K/Akt signaling and GTPase downstream of TG2
      activated Akt. The coupling of TG2 and GD3 production was specifically suppressed
      by prazosin (alpha1-AR antagonist), but not by propranolol (beta-AR antagonist)
      or rauwolscine (alpha2-AR antagonist), indicating alpha1-AR specificity. Small
      interfering RNA (siRNA) experiment results indicated that the alpha1-AR/TG2
      mediated signaling pathway activated PKCs alpha and delta to induce GD3 synthase
      gene expression. Transcription factors CREB, AP-1, and NF-kappaB regulated GD3
      synthase gene expression during alpha1-AR-induced differentiation in CML K562
      cells. In addition, GD3 synthase gene expression was upregulated in TG2
      transfected cells via alpha1-AR with expression of erythroid lineage markers and
      benzidine-positive staining. alpha1-AR/TG2 signaling pathway-directed GD3
      production is a crucial step in erythroid differentiation of K562 cells and GD3
      interacts with alpha1-AR/TG2, inducing GD3/alpha1-AR/TG2-mediated erythroid
      differentiation. These results suggest that GD3, which acts as a membrane
      mediator of erythroid differentiation in CML cells, provides a therapeutic avenue
      for leukemia treatment.

PMID- 29069788
TI  - The sirtuin 6 prevents angiotensin II-mediated myocardial fibrosis and injury by
      targeting AMPK-ACE2 signaling.
AB  - Sirtuin 6 (SIRT6) is an important modulator of cardiovascular functions in health
      and diseases. However, the exact role of SIRT6 in heart disease is poorly
      defined. We hypothesized that SIRT6 is a negative regulator of angiotensin II
      (Ang II)-mediated myocardial remodeling, fibrosis and injury. The male Sprague
      Dawley rats were randomized to Ang II (200 ng/kg/min) infusion with an osmotic
      minipump and pretreated with recombinant plasmids adeno-associated viral vector
      (AAV)-SIRT6 (pAAV-SIRT6) or pAAV-GFP for 4 weeks. Ang II triggered downregulated
      levels of SIRT6 and angiotensin-converting enzyme 2 (ACE2) and upregulated
      expression of connective tissue growth factor (CTGF) and proinflammatory
      chemokine fractalkine (FKN), contributing to enhanced cardiac fibrosis and
      ultrastructural injury. Reduced levels of phosphorylated pAMPK-alpha, increased
      myocardial hypertrophy and impaired heart dysfunction were observed in both Ang
      II-induced hypertensive rats and ACE2 knockout rats, characterized with increases
      in heart weight and left ventricular (LV) posterior wall thickness and decreases
      in LV ejection fraction and LV fractional shortening. More importantly, pAAV
      SIRT6 treatment strikingly potentiated cardiac levels of pAMPKalpha and ACE2 as
      well as decreased levels of CTGF, FKN, TGFbeta1, collagen I and collagen III,
      resulting in alleviation of Ang II-induced pathological hypertrophy, myocardial
      fibrosis, cardiac dysfunction and ultrastructural injury in hypertensive rats. In
      conclusion, our findings confirmed cardioprotective effects of SIRT6 on
      pathological remodeling, fibrosis and myocardial injury through activation of
      AMPK-ACE2 signaling and suppression of CTGF-FKN pathway, indicating that SIRT6
      functions as a partial agonist of ACE2 and targeting SIRT6 has potential
      therapeutic importance for cardiac fibrosis and heart disease.

PMID- 29069786
TI  - The overexpression of salivary cytokeratins as potential diagnostic biomarkers in
      head and neck squamous cell carcinomas.
AB  - BACKGROUND: Cytokeratin (CK) intermediate filaments are demonstrated to have
      enormous potential in regulating cellular motility and cancer progression. There
      are more than 20 divergent CKs that have been identified, of which CK 8, 17, 18
      and 19 are reported to be elevated in the tumour biopsies of head and neck cancer
      squamous cell carcinoma (HNSCC) patients. However, CK expression profiles in the
      saliva of HNSCC patients have not been investigated. We aim to investigate the
      mRNA expression profiles of CKs in saliva collected from healthy controls, HPV
      negative and -positive HNSCC patients. METHODS: Oral rinse samples were collected
      from 42 cancer-free healthy controls (age-matched) and patients who have been
      diagnosed with HPV-negative (n = 20) and -positive (n = 48) HNSCC. RESULTS: Here,
      we report that the mRNA expression profiles of CKs differed in saliva collected
      from healthy controls and HNSCC patients. The mRNA expression levels of CK 8 and
      18 were significantly elevated in saliva collected from HPV-negative HNSCC
      patients; whilst, CK 17 and 19 were expressed at a higher mRNA level in saliva
      collected from HPV-positive HNSCC patients compared to healthy controls.
      Importantly, receiver operating characteristic (ROC) analysis showed salivary CK
      8 and 18 to have superior sensitivity and specificity in discriminating the HPV
      negative HNSCC patients from healthy controls (80% and 86%) as well as between
      HPV-negative and -positive HNSCC patients (75% and 81%). CONCLUSION: In summary,
      we have demonstrated that an aberrant expression of salivary CKs may serve as a
      potential non-invasive diagnostic biomarker in HNSCC.

PMID- 29069787
TI  - Proteasome inhibitors prevent bi-directional HER2/estrogen-receptor cross-talk
      leading to cell death in endocrine and lapatinib-resistant HER2+/ER+ breast
      cancer cells.
AB  - Amplification and/or overexpression of the human epidermal growth factor 2 (HER2)
      oncogene occurs in about 13-15% of invasive breast cancer and triggers breast
      cancer cell proliferation, survival and metastatic progression. Around half of
      all breast cancers with HER2 overexpression co-express hormone receptors (HR)
      such as those for estrogen and progesterone. Aberrant signaling through HER2 and
      other members of the HER-family mediates endocrine-resistance in estrogen
      receptor alpha (ERalpha) positive breast cancer. On the other hand, ERalpha co
      expression has been shown to attenuate the efficiency of anti-HER2 therapies.
      These findings indicate that HER2 and ERalpha synergize to escape from both anti
      ERalpha and anti-HER2-targeted therapies. Rationally designed clinical trials
      that combine endocrine therapy with anti-HER2 agents to interfere with
      HER2/ERalpha cross-talk have been conducted. However, the outcome of these trials
      suggests that novel therapeutic approaches are needed to further improve
      inhibition of HER2 and other HER-family members in conjunction with a more
      efficient ERalpha blockade. Here, we demonstrate that carfilzomib and bortezomib
      stabilize the HER2-specific protein tyrosine phosphatase BDP1 leading to
      decreased HER2 autophosphorylation, reduced HER2 activity and subsequently
      attenuated activation of the PI3K/Akt-pathway, together with blockade of ERalpha
      expression. We further observed that proteasome inhibitors (PIs) reverse
      autophosphorylation and thereby inhibit the activity of constitutively active
      mutant HER2. We also demonstrate that PIs cause cell death in lapatinib and
      endocrine-resistant HER2+/ER+ breast cancer cells. These findings suggest that
      PIs might have the potential to improve the management of HER2+/ER+ breast cancer
      patients by efficiently disrupting the bi-directional HER2/ERalpha cross-talk.

PMID- 29069785
TI  - [10]-gingerol induces apoptosis and inhibits metastatic dissemination of triple
      negative breast cancer in vivo.
AB  - There is increasing interest in the use of non-toxic natural products for the
      treatment of various pathologies, including cancer. In particular, biologically
      active constituents of the ginger oleoresin (Zingiber officinale Roscoe) have
      been shown to mediate anti-tumour activity and to contribute to the anti
      inflammatory, antioxidant, antimicrobial, and antiemetic properties of ginger.
      Here we report on the inhibitory properties of [10]-gingerol against metastatic
      triple negative breast cancer (TNBC) in vitro and in vivo. We show that [10]
      gingerol concentration-dependently induces apoptotic death in mouse and human
      TNBC cell lines in vitro. In addition, [10]-gingerol is well tolerated in vivo,
      induces a marked increase in caspase-3 activation and inhibits orthotopic tumour
      growth in a syngeneic mouse model of spontaneous breast cancer metastasis.
      Importantly, using both spontaneous and experimental metastasis assays, we show
      for the first time that [10]-gingerol significantly inhibits metastasis to
      multiple organs including lung, bone and brain. Remarkably, inhibition of brain
      metastasis was observed even when treatment was initiated after surgical removal
      of the primary tumour. Taken together, these results indicate that [10]-gingerol
      may be a safe and useful complementary therapy for the treatment of metastatic
      breast cancer and warrant further investigation of its efficacy, either alone or
      in combination with standard systemic therapies, in pre-clinical models of
      metastatic breast cancer and in patients.

PMID- 29069795
TI  - Variants of GSK3beta and SFRP4 genes in Wnt signaling were not associated with
      osteonecrosis of the femoral head.
AB  - Genome-wide association studies have identified that the gene variants in Wnt
      signaling associate with bone mineral density and fracture risk but the effects
      of the variants on the development of osteonecrosis of the femoral head (ONFH)
      have been unclear. Here, we analyzed the polymorphisms of 4 variants in GSK3beta
      and SFRP4 genes of Wnt signaling and their association with the development of
      ONFH through Mass ARRAY(r) platform in 200 ONFH patients and 177controls in
      Chinese population. Our results showed that the genotypes and allele frequencies
      of all variants detected in SFRP4 and GSK3beta genes were not significantly
      different between patients and controls (p > 0.05); the correlation analysis
      between the 4 variants genotypes and gender, age at onset, etiological
      classification, unilateral or bilateral hip lesions, and clinical stages of ONFH,
      respectively, did not confirm significant association (p > 0.05) although age at
      onset in the minor homozygous(CC) carriers of SFRP4 rs1052981 (T/C) was a
      statistically younger tendency than that of the major homozygous (TT) or
      heterozygous (TC) of the SNP (p = 0.051); moreover, all haplotypes analyzed and
      their association with the clinical phenotypes of ONFH were also shown no
      statistical significance (p > 0.05).These results suggest that the 4 variants
      analyzed by this study in GSK3beta and SFRP4 genes of Wnt signaling pathway are
      unlikely to be associated with susceptibility to ONFH.

PMID- 29069798
TI  - Efficient cell death induction in human glioblastoma cells by photodynamic
      treatment with Tetrahydroporphyrin-Tetratosylat (THPTS) and ionizing irradiation.
AB  - BACKGROUND: So far, glioblastomas cannot be cured by standard therapy and have an
      extremely poor median survival of about 15 months. The photodynamic therapy (PDT)
      with next generation photosensitizers, reaching a higher therapeutic depth, might
      offer a new, adjuvant treatment strategy in brain cancer therapy. Here, we
      investigated the effect of THPTS-PDT combined with ionizing irradiation (IR) on
      glioblastoma cells in vitro and in vivo. RESULTS: THPTS colocalized to
      mitochondria and was not found in the nucleus. THPTS (2-20 MUg/ml)-PDT
      significantly reduced the proliferation, metabolic activity and clonogenic
      survival and induced cell death mainly through apoptosis and autophagy. THPTS-PDT
      combined with IR decreased the clonogenicity significantly compared to single
      treatments. THPTS (<= 300 MUg/ml) alone showed no dark toxicity. The maximum
      therapeutic depth of THPTS-PDT in C6 glioblastomas was 13 mm. MATERIALS AND
      METHODS: Three human glioblastoma cell lines (U-87 MG, A-172, DBTRG-05MG) were
      incubated with THPTS (1-300 MUg/ml) 3-24 hours before laser treatment (760 nm, 30
      J/cm2). THPTS localization and effects on metabolic activity, proliferation, cell
      death mechanisms and long-term reproductive survival were assessed. IR was
      conducted on an X-ray unit (0.813 Gy/min). Results were verified in vivo on a
      subcutaneous C6 glioblastoma model in Wistar rats. CONCLUSIONS: This study
      demonstrated efficient THPTS-PDT in glioblastoma cells, in vitro and in vivo. The
      combinatorial effects of THPTS-PDT and IR are of specific clinical interest as
      enhanced eradication of infiltrating glioblastoma cells in the tumor surrounding
      tissue might possibly reduce the commonly occurring local relapses.

PMID- 29069790
TI  - Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast
      cancer cell migration through an oscillatory Ca2+ signal.
AB  - Breast cancer remains a research priority due to its invasive phenotype. Although
      the role of ion channels in cancer is now well established, the role of inositol
      (1,4,5)-trisphosphate (IP3) receptors (IP3Rs) remains enigmatic. If the three
      IP3Rs subtypes expression have been identified in various cancers, little is
      known about their physiological role. Here, we investigated the involvement of
      IP3R type 3 (IP3R3) in the migration processes of three human breast cancer cell
      lines showing different migration velocities: the low-migrating MCF-7 and the
      highly migrating and invasive MDA-MB-231 and MDA-MB-435S cell lines. We show that
      a higher IP3R3 expression level, but not IP3R1 nor IP3R2, is correlated to a
      stronger cell line migration capacity and a sustained calcium signal.
      Interestingly, silencing of IP3R3 highlights an oscillating calcium signaling
      profile and leads to a significant decrease of cell migration capacities of the
      three breast cancer cell lines. Conversely, stable overexpression of IP3R3 in MCF
      7 cells significantly increases their migration capacities. This effect is
      completely reversed by IP3R3 silencing. In conclusion, we demonstrate that IP3R3
      expression level increases the migration capacity of human breast cancer cells by
      changing the calcium signature.

PMID- 29069793
TI  - Imprinting disorder in donor cells is detrimental to the development of cloned
      embryos in pigs.
AB  - Imprinting disorder during somatic cell nuclear transfer usually leads to the
      abnormality of cloned animals and low cloning efficiency. However, little is
      known about the role of donor cell imprinting in the development of cloned
      embryos. Here, we demonstrated that the imprinting (H19/Igf2) in porcine fetus
      fibroblasts derived from the morphologically abnormal cloned fetuses (the
      abnormal imprinting group) was more hypomethylated, and accordingly,
      significantly higher H19 transcription and lower Igf2 expression occurred in
      comparison with those in fibroblasts derived from morphologically normal cloned
      fetuses (the normal imprinting group) or donor fetus fibroblasts (the control
      group). When these fibroblasts were used as donor cells, the abnormal imprinting
      group displayed an even lower imprinting methylation level, in correspondence to
      the significantly downregulated expression of Dnmt1, Dnmt3a and Zfp57, and a
      markedly reduced blastocyst rate, while the normal imprinting group took on the
      similar patterns of imprinting, gene expression and embryo development to the
      control group. When 5-aza-dC was applied to reduce the fibroblasts imprinting
      methylation level in the normal imprinting group, cloned embryos displayed the
      more severely impaired imprinting and significantly lower blastocyst rate. While
      the upregulated H19 transcription in the abnormal imprinting group was knocked
      down, the imprinting statuses were partly rescued, and the cleavage and
      blastocyst rates significantly increased in cloned embryos. In all, donor cell
      imprinting disorder reduced the developmental efficiency of cloned embryos. This
      work provides a new insight into understanding the molecular mechanism of donor
      cells regulating the cloned embryo development.

PMID- 29069794
TI  - Association between MPHOSPH6 gene polymorphisms and IgA nephropathy risk in a
      Chinese Han population.
AB  - Multiple genetic and environmental factors together contribute to the risk of IgA
      nephropathy (IgAN). MPHOSPH6 play an important role in the recruitment of the
      exosome to the pre-rRNA. However, to date, little information is found about the
      association between MPHOSPH6 polymorphisms and the IgAN risk. In this case
      control study, we genotyped five single nucleotide polymorphisms (SNPs) in
      MPHOSPH6 gene in 416 IgAN cases and 495 controls using Sequenom Mass-ARRAY
      technology and evaluated their association with IgAN using the chi2 and genetic
      model analysis. In the allelic model analysis, we determined rs1056654 was
      associated with a 0.774-fold decrease in the risk of IgAN (95%CI= 0.630-0.952; p
      = 0.015). In the genetic model analysis, we found that the "C/C" genotype of
      rs1056675 was associated with an increased risk of IgAN based on the codominant
      model (OR =1.48; 95% CI=1.03-2.13; p=0.033) and recessive model (OR =1.52; 95%
      CI=1.11-2.09; p=0.0095). The "G/A-A/A" genotype of rs1056654 was associated with
      a decreased risk of IgAN based on the dominant model (OR =0.75; 95% CI=0.58-0.98;
      p=0.032) and log-additvie model (OR =0.78; 95% CI=0.64-0.96; p=0.0188). Our data
      suggested that gene polymorphisms in the MPHOSPH6 may exert influences IgAN
      susceptibility in a Chinese Han population.

PMID- 29069797
TI  - MicroRNA-16-5p overexpression suppresses proliferation and invasion as well as
      triggers apoptosis by targeting VEGFA expression in breast carcinoma.
AB  - MicroRNAs (miRNAs), a class of small noncoding RNA molecules, can manipulate the
      expressions of endogenous tumor-related genes, and are implicated in the
      development and progression of a wide type of tumors. In this study, the
      investigation from real-time quantitative PCR revealed that miRNA-16-5p was
      downregulated in breast carcinoma tissues and cells, coupled with the elevations
      of HIF-alpha and VEGFA protein expressions, compared with normal tissues.
      Lentiviral armed with miR-16-5p markedly increased the miR-16-5p levels in MCF-7
      and MDA-MB-231 cells, compared to blank and NC groups, and miR-16-5p
      overexpression significantly inhibited the proliferation and colony formation in
      MCF-7 and MDA-MB-231 cells. Besides, miR-16-5p upregulation markedly induced
      apoptosis and reduced invasion ability in MCF-7 and MDA-MB-231 cells. Notably,
      VEGFA was direct target of miR-16-5p. Stepwise investigation from in vitro and in
      vivo experiments demonstrated that miR-16-5p overexpression suppressed tumor
      growth and reduced HIF-alpha and VEGFA expressions in breast carcinoma cells and
      nude mice tumor tissues. These findings provide novel insights into molecular
      mechanism involved in the roles of miR-16-5p in tumor development and progression
      of breast carcinoma, and thus manipulation of miR-16-5p may be a novel potential
      therapeutic target for future therapies of the patients with breast carcinoma.

PMID- 29069791
TI  - Immunohistochemical biomarkers and volumetric parameters for predicting
      radiotherapy-based outcomes in patients with p16-negative pharyngeal cancer.
AB  - BACKGROUND: This study determined the prognostic effects of immunohistochemical
      biomarkers and volumetric parameters predicting radiotherapy-based treatment in
      patients with p16-negative squamous cell carcinoma of the oropharynx or
      hypopharynx. RESULTS: VEGF immunoreactivity > 2 and GLUT1 overexpression were
      prognostic factors for lower cause-specific survival. Moreover, both factors were
      associated with lower disease-free survival. The predictors of lower primary
      relapse-free survival were VEGF immunoreactivity > 2 and CT-based gross tumor
      volume > 16 mL. MATERIALS AND METHODS: Immunohistochemical biomarkers in
      pretreatment biopsy specimens from 60 patients with p16-negative cancer were
      analyzed using tissue microarrays. Computed tomography (CT)-based and biological
      tumor volumes were retrieved through fluorodeoxyglucose positron emission
      tomography-CT. Correlations of cause-specific, disease-free, and primary relapse
      free survival with volumetric parameters and the immunohistochemical biomarker
      score were investigated. CONCLUSIONS: For patients with p16-negative pharyngeal
      cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and
      GLUT1 expression and CT-based gross tumor volume.

PMID- 29069799
TI  - Functional compatibility between Purkinje cell axon branches and their target
      neurons in the cerebellum.
AB  - A neuron sprouts an axon, and its branches to innervate many target neurons that
      are divergent in their functions. In order to efficiently regulate the
      diversified cells, the axon branches should differentiate functionally to be
      compatible with their target neurons, i.e., a function compatibility between
      presynaptic and postsynaptic partners. We have examined this hypothesis by using
      electrophysiological method in the cerebellum, in which the main axon of Purkinje
      cell projected to deep nucleus cells and the recurrent axons innervated the
      adjacent Purkinje cells. The fidelity of spike propagation is superior in the
      recurrent branches than the main axon. The capabilities of encoding spikes and
      processing GABAergic inputs are advanced in Purkinje cells versus deep nucleus
      cells. The functional differences among Purkinje's axonal branches and their
      postsynaptic neurons are preset by the variable dynamics of their voltage-gated
      sodium channels. In addition, activity strengths between presynaptic and
      postsynaptic partners are proportionally correlated, i.e., active axonal branches
      innervate active target neurons, or vice versa. The physiological impact of the
      functional compatibility is to make the neurons in their circuits to be activated
      appropriately. In conclusion, each cerebellar Purkinje cell sprouts the
      differentiated axon branches to be compatible with the diversified target cells
      in their functions, in order to construct the homeostatic and efficient units for
      their coordinated activity in neural circuits.

PMID- 29069796
TI  - Nomogram for prediction of level 2 axillary lymph node metastasis in proven level
      1 node-positive breast cancer patients.
AB  - BACKGROUND: The current management of the axilla in level 1 node-positive breast
      cancer patients is axillary lymph node dissection regardless of the status of the
      level 2 axillary lymph nodes. The goal of this study was to develop a nomogram
      predicting the probability of level 2 axillary lymph node metastasis (L-2-ALNM)
      in patients with level 1 axillary node-positive breast cancer. MATERIALS AND
      METHODS: We reviewed the records of 974 patients with pathology-confirmed level 1
      node-positive breast cancer between 2010 and 2014 at the Liaoning Cancer Hospital
      and Institute. The patients were randomized 1:1 and divided into a modeling group
      and a validation group. Clinical and pathological features of the patients were
      assessed with uni- and multivariate logistic regression. A nomogram based on
      independent predictors for the L-2-ALNM identified by multivariate logistic
      regression was constructed. RESULTS: Independent predictors of L-2-ALNM by the
      multivariate logistic regression analysis included tumor size, Ki-67 status,
      histological grade, and number of positive level 1 axillary lymph nodes. The
      areas under the receiver operating characteristic curve of the modeling set and
      the validation set were 0.828 and 0.816, respectively. The false-negative rates
      of the L-2-ALNM nomogram were 1.82% and 7.41% for the predicted probability cut
      off points of < 6% and < 10%, respectively, when applied to the validation group.
      CONCLUSIONS: Our nomogram could help predict L-2-ALNM in patients with level 1
      axillary lymph node metastasis. Patients with a low probability of L-2-ALNM could
      be spared level 2 axillary lymph node dissection, thereby reducing postoperative
      morbidity.

PMID- 29069801
TI  - Effect of weekly or daily dosing regimen of Gefitinib in mouse models of lung
      cancer.
AB  - Gefitinib showed response in phase II clinical trials and with better clinical
      response in lung cancer with activating mutations in the tyrosine kinase domain
      of the EGFR. Questions of toxicity and potential dosing regimens impede the use
      in a prevention setting. This study will provide scientific evidence for the
      utility of testing and comparing weekly and daily dosing regimens in clinical
      trials. We employed the adenocarcinoma (AD) and squamous cell carcinoma (SCC)
      models to compare the efficacy of Gefitinib in daily or weekly dosing regimens.
      We also assessed the effectiveness of Gefitinib in altering growth of the H3255
      xenograft. Bioluminescent imaging (BLI) and tumor size was evaluated. Relative
      expression of phospho-EGFR, phospho-ERK and phospho-AKT in the xenograft were
      evaluated by Western Blot analysis. In the lung AD model, Gefitinib showed
      significant inhibition of tumor load when treated with weekly or weekly
      intermittent dosing regimens in AJ/p53 val135/wt mice whereas a daily dosing
      regimen did not decrease the tumor load significantly. In the H3255-Luciferase
      xenograft model, weekly treatment demonstrated better inhibition than daily
      treatment. The weekly dosing regimen exhibited greater inhibition of phospho
      EGFR, phospho-ERK and phospho-AKT than the daily dosing regimen, which may be
      correlated with the antitumor effects of the different dosing regimens. Weekly
      dosing with Gefitinib had similar or better efficacy than the daily dosing
      regimen in pre-clinical models of NSCLC. The data provide scientific evidences
      for the utility of testing and comparing weekly and intermittent dosing regimens
      in clinical trials.

PMID- 29069803
TI  - The significance of ENAH in carcinogenesis and prognosis in gastric cancer.
AB  - The ENAH gene, which encodes a member of the enabled/vasodilator-stimulated
      phosphoprotein (Ena/VASP) family of proteins, is involved in the assembly of
      actin filaments required for cell adhesion and motility. Recent studies show
      overexpressed ENAH in several cancer types, and ENAH correlates with tumor
      invasiveness. This study aimed to investigate the expression and function of ENAH
      in primary gastric adenocarcinoma, and its prognostic significance. We found
      significantly increased mRNA (P = 0.0283) and protein (P = 0.0301) expression of
      ENAH in gastric cancer tissues. ENAH expression markedly associated with tumor
      size (P < 0.001), T stage (P < 0.001), N stage (P = 0.001), TNM stage (P < 0.001)
      and prognosis (P < 0.001). Cox regression analyses revealed ENAH expression as an
      independent predictor of overall survival (P = 0.019). We also analyzed data of
      155 gastric cancer cases from The Cancer Genome Atlas (TCGA) and found that ENAH
      expression significantly correlated with age (P = 0.003), T stage (P = 0.023) and
      prognosis (P = 0.05). Furthermore, the function of ENAH in cell proliferation,
      colony formation, cell migration and invasion of gastric cancer cells was
      analyzed in vitro. Knockdown of ENAH expression suppressed cell proliferation,
      colony formation, cell migration and invasion in MKN45 cells. Conversely,
      overexpression of ENAH promoted cell proliferation, cell migration and invasion
      in MGC803 cells. Our research suggests that ENAH might play promoting functions
      in carcinogenesis and progression of gastric cancer, and may serve as a valuable
      prognostic marker for primary gastric adenocarcinoma patients.

PMID- 29069800
TI  - Evaluation of cytology versus human papillomavirus-based cervical cancer
      screening algorithms in Bhutan.
AB  - To evaluate the performance of existing versus alternative cervical cancer
      screening protocols in Bhutan, cervical exfoliated cells were collected for
      cytology and high-risk human papillomavirus (HR-HPV) testing among 1,048 women
      aged 30-69 years. Conventional smears were prepared and read locally. HR-HPV was
      tested by GP5+/6+ polymerase chain reaction, followed by genotyping and human DNA
      methylation analysis among HR-HPV-positives, in Europe. Test positivity was 7.5%
      for ASCUS or worse (ASCUS+) cytology and 14.0% for HR-HPV. All women with ASCUS+
      and/or HR-HPV positivity (n=192) were recalled for colposcopy, among whom a total
      of 29 cases of histologically confirmed cervical intraepithelial neoplasia grade
      2 or worse (CIN2+) were identified. An additional 7 CIN2+ cases were imputed
      among women without colposcopy. Corrected sensitivities for CIN2+ and CIN3+ were
      61% and 74% for ASCUS+, 86% and 96% for HR-HPV, and 47% and 70% for ASCUS+ triage
      of HR-HPV. Specificity varied from 88% for HR-HPV up to 98% for ASCUS+ triage of
      HR-HPV, similarly for CIN2+ and CIN3+. Among HR-HPV-positive women with biopsies,
      methylation analysis offered similar discrimination of CIN2/3 and cervical cancer
      as ASCUS+, and better than HPV16/18 genotyping alone, but sample sizes were
      limited. In conclusion, the performance of cytology in Bhutan is in the mid-range
      of that reported in other screening settings. HR-HPV testing has the potential to
      improve detection of CIN2+, albeit with a higher referral rate for colposcopy.
      Cytological triage of HR-HPV-positives (performed in the absence of knowledge of
      HR-HPV status) reduced referral but missed more than one third of CIN2+.

PMID- 29069792
TI  - Acquired somatic TP53 or PIK3CA mutations are potential predictors of when polyps
      evolve into colorectal cancer.
AB  - Colorectal cancer (CRC) develops from accumulated mutations. However, which gene
      determines the malignant transformation from adenoma to carcinoma is still
      uncertain. Fifty-three formalin fixed paraffin-embedded polyps that had
      pathological findings from patients with hyperplasia, adenomatous, and tubular
      adenoma < 1 cm (non-neoplasia polyps, NNP, n = 27) or tubular adenoma >= 1 cm,
      tubulovillous and villous adenoma (neoplastic polyps, NP, n = 26) were recruited.
      Six paired synchronous polyps and cancer tissues and 50 independent fresh CRC
      tumors were also collected. All tissues were analyzed for their mutation genomes
      using next generation sequencing with a 50-gene panel. There were 40 types of
      somatic variants found in 7 genes, APC (43%), KRAS (28%), TP53 (11%), FBXW7 (8%),
      GNAS (4%), SMAD4 (2%), and BRAF (2%), and they were detected in 32 (60%) polyps.
      If combined with the mutation spectrum found in CRC tissues, a significant
      increase in the mutation rate in TP53 and PIK3CA from NNP, NP, early and late
      stage carcinoma (7%, 15%, 33.3% and 65% for TP53, p < 0.001; 0%, 0%, 23.3% and
      25% for PIK3CA, p = 0.002) were noticed. Furthermore, distinct molecular features
      can be found in five pairs of synchronous polyps and tumors. However, TP53 or
      PIK3CA mutations can be found in tumor tissues but not in polyps. By
      systematically investigating the genome from polyps to tumor tissues, we
      demonstrated that acquired TP53 or PIK3CA somatic mutations are potential
      predictors for malignancy development. These results may aid in the
      identification of high risk individuals with tissues harboring mutations in these
      two genes.

PMID- 29069802
TI  - Advanced nasopharyngeal carcinoma: pre-treatment prediction of progression based
      on multi-parametric MRI radiomics.
AB  - We aimed to investigate the potential of radiomic features of magnetic resonance
      imaging (MRI) to predict progression in patients with advanced nasopharyngeal
      carcinoma (NPC). One hundred and thirteen consecutive patients (01/2007-07/2013)
      (training cohort: n = 80; validation cohort: n = 33) with advanced NPC were
      enrolled. A total of 970 initial features were extracted from T2-weighted (T2-w)
      (n = 485) and contrast-enhanced T1-weighted (CET1-w) MRI (n = 485) for each
      patient. We used least absolute shrinkage and selection operator (Lasso) method
      to select features that were most significantly associated with the progression.
      The selected features were used to construct radiomics-based models and the
      predictive performance of which were assessed with respect to the area under the
      curve (AUC). As a result, eight features significantly associated with the
      progression of advanced NPC were identified. In the training cohort, a radiomic
      model based on combined CET1-w and T2-w images (AUC: 0.886, 95%CI: 0.815-0.956)
      demonstrated better prognostic performance than models based on CET1-w (AUC:
      0.793, 95%CI: 0.698-0.889) or T2-w images alone (AUC: 0.813, 95%CI: 0.721-0.904).
      These results were confirmed in the validation cohort. Accordingly, MRI-based
      radiomic biomarkers present high accuracy in the pre-treatment prediction of
      progression in advanced NPC.

PMID- 29069806
TI  - Modulating BAP1 expression affects ROS homeostasis, cell motility and
      mitochondrial function.
AB  - The tumor suppressor BAP1 associates with ASXL1/2 to form the core Polycomb
      complex PR-DUB, which catalyzes the removal of mono-ubiquitin from several
      substrates including histone H2A. This complex also mediates the poly
      deubiquitination of HCFC1, OGT and PCG1-alpha, preventing them from proteasomal
      degradation. Surprisingly, considering its role in a Polycomb complex, no
      transcriptional signature was consistently found among BAP1-inactivated tumor
      types. It was hypothesized that BAP1 tumor suppressor activity could reside, at
      least in part, in stabilizing proteins through its poly-deubiquitinase activity.
      Quantitative mass spectrometry and gene expression arrays were used to
      investigate the consequences of BAP1 expression modulation in the NCI-H226
      mesothelioma cell line. Analysis of differentially expressed proteins revealed
      enrichment in cytoskeleton organization, mitochondrial activity and ROS
      management, while gene expression analysis revealed enrichment in the epithelial
      to-mesenchymal transition pathway. Functional assessments in BAP1 inactivated,
      BAP1 wild-type and BAP1 catalytically dead-expressing NCI-H226 and QR
      mesothelioma cell lines confirmed alteration of these pathways and demonstrated
      that BAP1 deubiquitinase activity was mandatory to maintain these phenotypes.
      Interestingly, monitoring intracellular ROS levels partly restored the morphology
      and the mitochondrial activity. Finally, the study suggests new tumorigenic and
      cellular functions of BAP1 and shows for the first time the interest of studying
      the proteome as readout of BAP1 inactivation.

PMID- 29069804
TI  - Progesterone receptor membrane component 1 is phosphorylated upon progestin
      treatment in breast cancer cells.
AB  - Menopausal hormone therapy, using estrogen and synthetic progestins, is
      associated with an increased risk of developing breast cancer. The effect of
      progestins on breast cells is complex and not yet fully understood. In previous
      in vitro and in vivo studies, we found different progestins to increase the
      proliferation of Progesterone Receptor Membrane Component-1 (PGRMC1)
      overexpressing MCF7 cells (MCF7/PGRMC1), suggesting a possible role of PGRMC1 in
      transducing membrane-initiated progestin signals. Understanding the activation
      mechanism of PGRMC1 by progestins will provide deeper insights into the mode of
      action of progestins on breast cells and the often-reported phenomenon of
      elevated breast cancer rates upon progestin-based hormone therapy. In the present
      study, we aimed to further investigate the effect of progestins on receptor
      activation in MCF7 and T47D breast cancer cell lines. We report that treatment of
      both breast cancer cell lines with the progestin norethisterone (NET) induces
      phosphorylation of PGRMC1 at the Casein Kinase 2 (CK2) phosphorylation site
      Ser181, which can be decreased by treatment with CK2 inhibitor quinalizarin.
      Point mutation of the Ser181 phosphorylation site in MCF7/PGRMC1 cells impaired
      proliferation upon NET treatment. This study gives further insights into the
      mechanism of differential phosphorylation of the receptor and confirms our
      earlier hypothesis that phosphorylation of the CK2-binding site is essential for
      activation of PGRMC1. It further suggests an important role of PGRMC1 in the
      tumorigenesis and progression of breast cancer in progestin-based hormone
      replacement therapy.

PMID- 29069805
TI  - Epidermal growth factor receptor activity is elevated in glioma cancer stem cells
      and is required to maintain chemotherapy and radiation resistance.
AB  - Glioblastoma remains among the most aggressive of all human and canine
      malignancies, displaying high mortality rates and limited treatment options. We
      propose that given the similarities between canine and human gliomas, such as
      incidence of occurrence, histopathology, molecular characteristics, and response
      to therapy, that canine gliomas are a natural model of the human disease. A range
      of human and canine tumours have been shown to harbor specific subpopulations of
      cells with stem cell-like properties that initiate and maintain neoplasticity
      while resisting conventional therapies. Here, we show that both canine and human
      glioma cell lines contain a small population of cancer stem cells (CSCs), and by
      molecular profiling highlight the important role of the epidermal growth factor
      receptor (EGFR) pathway in canine CSCs. EGFR signaling is crucial in the
      regulation of cancer cell proliferation, migration and survival. To date EGFR
      targeted interventions alone have been largely ineffective. Our findings confirm
      that specifically inhibiting EGFR signaling alone has no significant effect on
      the viability of CSCs. However inhibition of EGFR did enhance the chemo- and
      radio-sensitivity of both canine and human glioma CSCs, enabling this resistant,
      tumourigenic population of cells to be effectively targeted by conventional
      therapies.

PMID- 29069807
TI  - Chronic high dose of captopril induces depressive-like behaviors in mice:
      possible mechanism of regulatory T cell in depression.
AB  - Major depression has various types of symptoms and disease courses with
      inconsistent response to monoamine-related antidepressants. Thus, monoamine
      theory may not be the only pathophysiologic pathway relevant to depression.
      Recently, it has been suggested that regulatory T cell (Treg) is associated with
      depression. Based on our previous study that showed decreased regulatory T cell
      (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day * 21
      days) administration, we examined whether CHC alone can induce depressive-like
      behaviors in mice even without stressful stimuli. In this study, we found that
      CHC induced depressive-like behaviors in tail suspension test (TST) and forced
      swimming test (FST) without systemic illness, while it did not induce anhedonic
      behavior, anxiety-like behaviors, or sociality-related behavior. The depressive
      like behaviors were rescued by either CHC washout or antidepressant. CHC caused
      reduction in foxp3 and gata3 mRNA expression in the lymph nodes with elevation in
      plasma IL-1beta and IL-6. Interestingly, CHC increased serum angiotensin II
      level. In the hippocampus, CHC increased TNF-alpha and IL-6 mRNA expression with
      microglia activation while reduced glucocorticoid receptor expression. However,
      CHC did not affect to hippocampal kynurenine pathway, serotonin level,
      hypothalamic corticotropin-releasing hormone mRNA level, or serum corticosterone
      level. Consequently, we propose that CHC may induce a specific form of depressive
      like behaviors via Treg reduction and microglial activation.

PMID- 29069808
TI  - Targeting the cancer stem cell marker, aldehyde dehydrogenase 1, to circumvent
      cisplatin resistance in NSCLC.
AB  - Non-small cell lung cancer (NSCLC) accounts for a large proportion of cancer
      deaths and is characterized by low treatment response rates and poor overall
      prognosis. In the absence of specific treatable mutations, cisplatin-based
      chemotherapy plays an important role in the treatment of this disease.
      Unfortunately, the development of resistance has become a major therapeutic
      challenge in the use of this cytotoxic drug. Elucidating the mechanisms
      underlying this resistance phenotype, may result in the development of novel
      agents that enhance sensitivity to cisplatin in lung cancer patients. In this
      study, targeting the cancer stem cell activity of aldehyde dehydrogenase 1
      (ALDH1) was investigated as a strategy to overcome chemoresistance in NSCLC.
      Tumors from NSCLC patients showed an increase in their profile of pluripotent
      stemness genes. Cisplatin exposure induced the emergence or expansion of an ALDH1
      positive subpopulation in cisplatin sensitive and resistant NSCLC cell lines,
      respectively, further enhancing cisplatin resistance. Using the Aldefluor assay
      and FACS analysis, ALDH1 subpopulations were isolated and evaluated in terms of
      stem cell characteristics. Only ALDH1-positive cells exhibited asymmetric
      division, cisplatin resistance and increased expression of stem cell factors in
      vitro. Xenograft studies in NOD/SCID mice demonstrated efficient tumorigenesis
      from low cell numbers of ALDH1-positive and ALDH1-negative subpopulations.
      Targeting ALDH1 with Diethylaminobenzaldehyde (DEAB) and Disulfiram,
      significantly re-sensitized resistant lung cancer cells to the cytotoxic effects
      of cisplatin. Our data demonstrate the existence of a lung CSC population and
      suggest a role for targeting ALDH1 as a potential therapeutic strategy in re
      sensitizing NSCLC cells to the cytotoxic effects of cisplatin.

PMID- 29069810
TI  - The recurrence risk of neural tube defects (NTDs) in a population with high
      prevalence of NTDs in northern China.
AB  - BACKGROUND: Although a number of studies have reported the recurrence risk of
      NTDs in developed countries, there is little data on the rate of recurrence of
      NTDs in northern China, a region of high prevalence of NTDs. METHODS: Based on
      the population-based birth defects surveillance system of five counties, we
      identified women who had an NTD affected pregnancy from 2004-2015 and a
      retrospective survey was conducted. The rate of recurrence of NTDs was calculated
      by the number of recurrent NTDs divided by the first NTDs. Maternal age, body
      mass index (BMI), gestational weeks, education, and occupation were collected.
      Information on folic acid (FA) supplements, time and dosage were also recorded.
      RESULTS: Among 851 women who had a previous NTD-affected pregnancy, there were
      578 subsequent pregnancies, with 10 recurrent NTDs, a 1.7% recurrence rate. The
      recurrence rate was 1.5% and 2.6% for those taking FA supplements and without FA
      supplementation respectively. Women with recurrent NTDs had higher BMI before
      pregnancy compared to those who had a second pregnancy without NTDs. Among the
      recurrent NTDs, the majority were spina bifida. CONCLUSIONS: The recurrence rate
      of NTDs was approximately five times higher than the overall prevalence in the
      same region of northern China. Risk of recurrence appeared lower among women who
      took FA supplements. These findings are consistent with the reduction in NTD
      frequency in the population since introduction of the nationwide FA supplement
      program. Data on recurrence rates in northern China will inform power
      calculations for future intervention studies.

PMID- 29069809
TI  - Human papillomavirus dysregulates the cellular apparatus controlling the
      methylation status of H3K27 in different human cancers to consistently alter gene
      expression regardless of tissue of origin.
AB  - High-risk human papillomaviruses (HPV) cause cancer at multiple distinct
      anatomical locations. Regardless of the tissue of origin, most HPV positive
      (HPV+) cancers show highly upregulated expression of the p16 product of the
      cyclin-dependent kinase inhibitor 2A (CDKN2A) gene. Paradoxically, HPV+ tumor
      cells require continuous expression of this tumor suppressor for survival. Thus,
      restoration of normal p16 regulation has potential therapeutic value against HPV
      induced cancers. Normally, p16 transcription is tightly controlled at the
      epigenetic level via polycomb repressive complex-mediated tri-methylation of
      histone 3 lysine 27 (H3K27me3). Although a mechanism by which HPV induces p16 has
      been proposed based on tissue culture models, it has not been extensively
      validated in human tumors. In this study, we used data from over 800 human
      cervical and head and neck tumors from The Cancer Genome Atlas (TCGA) to test
      this model. We determined the impact of HPV status on expression from the CDKN2A
      locus, the adjacent CDKN2B locus, and transcript levels of key epigenetic
      regulators of these loci. As expected, HPV+ tumors from both anatomical sites
      exhibited high levels of p16. Furthermore, HPV+ tumors expressed higher levels of
      KDM6A, which demethylates H3K27me3. CpG methylation of the CDKN2A locus was also
      consistently altered in HPV+ tumors. This data validates previous tissue culture
      studies and identifies remarkable similarities between the effects of HPV on gene
      expression and DNA methylation in both cervical and oral tumors in large human
      cohorts. Furthermore, these results support a model whereby HPV-mediated
      dysregulation of CDKN2A transcription requires KDM6A, a potentially druggable
      target.

PMID- 29069811
TI  - Extracellular sphingomyelinase activity impairs TNF-alpha-induced endothelial
      cell death via ADAM17 activation and TNF receptor 1 shedding.
AB  - ADAM17, a prominent member of the "Disintegrin and Metalloproteinase" (ADAM)
      family, is an important regulator of endothelial cell proliferation and cell
      survival. The protease controls vital cellular functions through cleavage of
      growth factors, cytokines and their receptors including transforming growth
      factor-alpha (TGF-alpha), tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha
      receptor 1 (TNFR1). TNF-alpha is the major inducer of endothelial cell death in
      cardiovascular diseases. The latter are also characterized by elevated plasma and
      tissue levels of extracellular sphingomyelinase (SMase). Whether the SMase
      affects ADAM activity and thus endothelial cell function has not been addressed
      to date. Here, we analyzed the effect of SMase on ADAM17-mediated shedding in
      COS7 cells and in human umbilical vein endothelial cells (HUVECs). Exposure to
      SMase significantly increased ADAM17-mediated release of alkaline-phosphatase
      (AP)-tagged TGF-alpha in COS7 cells and shedding of endogenously expressed TNFR1
      in HUVECs. We previously presented evidence that surface exposure of
      phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase function. We
      found that SMase treatment led to PS externalization in both cell types.
      Transient non-apoptotic PS exposure is often mediated by Ca2+-dependent
      phospholipid scramblases. Accordingly, the Ca2+-chelator EGTA markedly reduced
      the breakdown of phospholipid asymmetry and shedding of TGF-alpha and TNFR1.
      Moreover, sheddase activity was significantly diminished in the presence of the
      competing PS-headgroup OPLS. SMase-stimulated TNFR1 shedding strikingly
      diminished TNF-alpha-induced signalling cascades and endothelial cell death.
      Taken together, our data suggest that SMase activity might act as protective
      factor for endothelial cells in cardiovascular diseases.

PMID- 29069812
TI  - M2 macrophages are more resistant than M1 macrophages following radiation therapy
      in the context of glioblastoma.
AB  - In some highly inflammatory tumors, such as glioblastoma (GB), macrophages (MPhi)
      represent the most abundant population of reactive cells. MPhi, initially denoted
      as M0 MPhi, can be polarized into two further phenotypes: the antitumor M1 MPhi,
      and the protumor M2 MPhi. The three phenotypes can reside simultaneously in the
      tumor mass and various external factors may influence MPhi polarization.
      Radiotherapy is a common modality of cancer treatment aiming to target tumor
      cells. However, the specific effects of X-ray radiation on the inflammatory cells
      are, so far, controversial and not fully understood. In the present
      investigation, we have first analyzed, in vivo, the effect of X-ray radiation on
      MPhi present in GB tumors. We have observed a decrease in MPhi number paralleled
      by an increase in the proportion of M2 MPhi. To understand this phenomenon, we
      then evaluated, in vitro, the effects of X-rays on the MPhi phenotypes and
      survival. We have found that X-ray radiation failed to modify the phenotype of
      the different MPhi. However, M1 MPhi were more sensitive to ionizing radiation
      than M2 MPhi, both in normoxia and in hypoxia, which could explain the in vivo
      observations. To conclude, M2 MPhi are more radioresistant than M0 and M1 MPhi
      and the present study allows us to propose that X-ray radiotherapy could
      contribute, along with other phenomena, to the increased density in the protumor
      M2 MPhi in GB.

PMID- 29069813
TI  - Transarterial chemoembolization (TACE) with degradable starch microspheres (DSM)
      in hepatocellular carcinoma (HCC): multi-center results on safety and efficacy.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the 3rd leading cause of cancer
      related death worldwide. The majority of HCCs are diagnosed in a stage that is
      not eligible for curative resection. For intermediate stage HCC, transarterial
      chemoembolization (TACE) is the recommended treatment. We evaluated the safety
      and efficacy of DSM (degradable starch microspheres) as embolic agent in
      transarterial chemoembolization (TACE) for the treatment of intermediate stage,
      non-resectable hepatocellular carcinoma (HCC). METHODS AND FINDINGS: A national,
      multi-center observational study on the safety and efficacy of DSM-TACE for the
      treatment of intermediate HCC was conducted. The recruitment period for the study
      was from January 2010 to June 2014. The primary endpoints were safety and
      treatment response according to the mRECIST criteria. A total of 179 DSM-TACE
      procedures in 50 patients were included in the analysis. The therapeutic efficacy
      assessed with mRECIST was as follows: complete response (n=1; 2 %), 21 partial
      response (42 %), 13 stable disease (26 %), 9 progressive disease (18 %), and 6
      incomplete data (12 %). Thus, the objective response rate was 44% (n=22) and
      disease control rate was 70% (n=35). A total of 76 immediate adverse events (AE)
      and 2 severe adverse events (SAE) were recorded. Forty-eight percent of patients
      (n=24) did not encounter any immediate AE/SAE. Between treatments, a total of 66
      AE and one SAE were recorded. Twenty-four patients (48 %) did not encounter any
      AE/SAE in between treatments. CONCLUSION: The use of DSM as a TACE embolic agent
      appears to be safe for the treatment of HCC and has promising efficacy.

PMID- 29069814
TI  - Circulating tumor DNA detection in head and neck cancer: evaluation of two
      different detection approaches.
AB  - The use of non-invasive biomarkers such as circulating tumor DNA (ctDNA) in head
      and neck tumors may be of relevance in early diagnosis and eventually improved
      outcome. We evaluated two different approaches from two case series in Europe and
      South America including (i) targeted screening of ctDNA mutations, and (ii)
      detection of TP53 mutations in plasma and oral rinses without previous knowledge
      of mutational status in tumor samples. Targeted sequencing in 5 genes identified
      ctDNA mutations in plasma among 42% of HNSCC cases, 67% of who were early stage
      cases. No association was found between ctDNA mutation detection and overall
      survival. Sequencing of the entire coding region of the TP53 gene resulted in
      identification of TP53 mutations in 76% of tumor cases. However, concordance of
      mutation detection was low between tumor, oral rinses (11%) and plasma (2,7%)
      samples. Identification of 5 pathogenic TP53 mutations in oral rinses from 3 non
      cancer controls gives additional evidence of mutation occurrence in individuals
      without a diagnosed cancer and presents an additional challenge for the
      development of ctDNA diagnostic assays.

PMID- 29069815
TI  - RPN2 promotes colorectal cancer cell proliferation through modulating the
      glycosylation status of EGFR.
AB  - Various studies have found that silencing ribophorin II (RPN2) inhibits cell
      growth in several cancers. However, the underlying mechanism by which RPN2
      regulates cancer cell proliferation remains unclear. Herein, we reveal that
      downregulation of RPN2, which may be a crucial regulator of N-linked
      glycosylation in cancer cells and drug-resistant cancer cells, promoted the
      progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and
      in vivo. We found that RPN2 silencing reduced glycosylation of EGFR, a highly N
      link glycosylated cell surface glycoprotein that plays a critical role in
      majority of human cancers correlating with increased cell growth, proliferation,
      and differentiation. In addition, RPN2 knockdown decreased EGFR expression and
      cell surface transport by EGFR deglycosylation. In summary, our findings suggest
      that RPN2 regulates CRC cell proliferation through mediating the glycosylation of
      EGFR which affecting the EGFR/ERK signaling pathways. Clinicopathological
      analysis showed that the overexpression of RPN2 and EGFR was positively
      correlated with colorectal tumor size. Therefore, RPN2 may be a new therapeutic
      target and prognostic biomarker for CRC.

PMID- 29069816
TI  - Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in
      HCC cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid
      progression and high mortality. However, chemotherapy of HCC is hindered by multi
      drug resistance (MDR). It is urgent, therefore, to explore new approaches for
      overcoming MDR of HCC cells. Ubenimex, an inhibitor of CD13, has been used as an
      immuno-enhancer for treating hematological neoplasms and other solid tumors.
      Here, we demonstrate that Ubenimex can also reverse MDR in the HCC cell lines
      HepG2/5-FU and Bel7402/5-FU. Ubenimex inhibits the expression of the proto
      oncogene, Pim-3, which is accompanied by decreased expression of BCL-2 and BCL
      XL, decreased phosphorylation of Bad, and increased tumor apoptosis. Moreover,
      Ubenimex decreases expression of the MDR-associated proteins P-gp, MRP3 and MRP2
      to enhance intracellular accumulation of Cisplatin, for which down-regulation of
      Pim-3 is essential. Our results reveal a previously uncharacterized function of
      Ubenimex in mediating drug resistance in HCC, which suggests that Ubenimex may
      provide a new strategy to reverse MDR and improve HCC sensitivity to
      chemotherapeutic drugs via its effects on Pim-3.

PMID- 29069817
TI  - Binase treatment increases interferon sensitivity and apoptosis in SiHa cervical
      carcinoma cells by downregulating E6 and E7 human papilloma virus oncoproteins.
AB  - In this study, we determined whether binase, a ribonuclease from Bacillus
      pumilus, increases interferon sensitivity and apoptosis in SiHa cervical cancer
      cells infected with high-risk human papilloma virus (HPV) strain 16. Binase
      treatment increased SiHa cell apoptosis in a time- and concentration-dependent
      manner, as determined by flow cytometry, WST tests and real time xCelligence cell
      index analysis. Binase-treated SiHa cells showed reduced expression of E6 and E7
      viral oncoproteins and increased expression of their intracellular targets, p53
      and pRb. Combined treatment with binase and IFNalpha2b enhanced the interferon
      sensitivity of HPV-positive SiHa cells. By contrast, combined treatment with
      binase and IFNalpha2b in HPV-negative C33A cervical cancer cells, which do no
      expess E6 and E7, elicited no changes in interferon sensitivity or p53 and pRb
      expression. These findings suggest binase enhances interferon sensitivity and
      apoptosis in HPV-positive SiHa cervical cancer cells by suppressing E6 and E7
      viral protein expression.

PMID- 29069818
TI  - Inhibiting PHD2 in bone marrow mesenchymal stem cells via lentiviral vector
      mediated RNA interference facilitates the repair of periodontal tissue defects in
      SD rats.
AB  - Hypoxia-inducible factors (HIFs) play an important role in angiogenesis, and they
      can activate the expression of several downstream angiogenic factors. HIF-1 is a
      major transcriptor of HIFs, composed of alpha and beta subunits. Prolyl
      hydroxylase domain-containing protein 2 (PHD2) is the main catabolic enzyme for
      HIF-1alpha, and it can accelerate its degradation under normoxic conditions. PHD2
      expression in bone marrow mesenchymal stem cells (BMMSCs) of SD rats was down
      regulated under normoxic conditions in this study by utilizing lentiviral vector
      mediated RNA interference to promote HIF-1alpha accumulation, thus enhancing the
      expression of angiogenic factors. A tissue-engineered compound was constructed
      using the composite collagen membrane of BMMSCs after PHD2 gene silencing to
      repair periodontal fenestration defects in SD rats. The results of this study
      indicated that, after PHD2 gene silencing, the osteogenic differentiation of
      BMMSCs was enhanced in vitro, the resistance of cells to oxidative stress was
      also validated in vitro, thereby illustrating the promotion of the repair of
      artificially constructed periodontal tissue defects in rats. The results of this
      study provide a reference and guidance for future applications of RNA
      interference in periodontal tissue engineering and serve as a basis for improving
      the survival of seed cells in recipient tissues.

PMID- 29069819
TI  - Comparison of twelve single-drug regimens for the treatment of type 2 diabetes
      mellitus.
AB  - We performed a network meta-analysis to compare the efficacy of 12 single-drug
      regimens (Glibenclamide, Glimepiride, Pioglitazone, Rosiglitazone, Repaglinide,
      Metformin, Sitaglitin, Exenatide, Liraglutide, Acarbose, Benfluorex, and
      Glipizide) in the treatment of type 2 diabetes mellitus (T2DM). Fifteen relevant
      randomized controlled trials (RCTs) were included; direct and indirect evidence
      from these studies was combined, and weighted mean difference (WMD) and surface
      under the cumulative ranking curves (SUCRAs) were examined to evaluate the
      monotherapies. Liraglutide was more effective than Glimepiride, Pioglitazone,
      Sitaglitin, Exenatide, and Glipizide at reducing glycated hemoglobin (HbA1c)
      levels. In contrast, Acarbose was less effective than Glibenclamide, Glimepiride,
      Pioglitazone, Rosiglitazone, Repaglinide, Metformin, and Liraglutide at
      decreasing HbA1c levels. Reductions in fasting plasma glucose (FPG) levels were
      similar after all treatments. Rosiglitazone was less effective than Glibenclamide
      and Repaglinide at reducing total cholesterol (TC) levels. High density
      lipoprotein (HDL), low density lipoprotein (LDL), and triglyceride levels did not
      differ after treatment with any of the monotherapies. HbA1c and FPG SUCRA values
      were highest for Liraglutide, while HbA1c and FPG values were lowest for
      Acarbose, and TC and LDL values were lowest for Rosiglitazone. These results
      suggest that Liraglutide may be most effective, and Acarbose least effective, at
      reducing blood glucose levels, while Glibenclamide, Repaglinide, and Metformin
      may be most effective, and Rosiglitazone least effective, at reducing lipoidemia,
      in T2DM patients.

PMID- 29069820
TI  - The influence of two functional genetic variants of GRK5 on tau phosphorylation
      and their association with Alzheimer's disease risk.
AB  - Our work explores the relationship between G protein-coupled receptor kinase-5
      (GRK5) single nucleotide polymorphisms and Alzheimer's disease risk. We confirmed
      that GRK5 translocates from the cellular membrane to the cytosol in the
      hippocampus of Alzheimer's disease mice and that GRK5 deficiency promotes tau
      hyperphosphorylation, a hallmark of Alzheimer's disease pathology. Our results
      indicate that one functional variant, or mutant, of GRK5 (GRK5-Gln41Leu)
      decreased GRK5 translocation from the membrane to the cytoplasm and reduced tau
      hyperphosphorylation, whereas, another GRK5 mutant (GRK5-Arg304His) increased
      GRK5 translocation to the cytoplasm and promoted tau hyperphosphorylation. In
      addition, case-control studies revealed that GRK5-Gln41Leu is associated with a
      lower risk of late-onset Alzheimer's disease. Our findings suggest that the GRK5
      Gln41Leu mutant may resist tau hyperphosphorylation by promoting GRK5 membrane
      stability and, in effect, may contribute to lower Alzheimer's disease risk.

PMID- 29069821
TI  - Combination treatment of ergosterol followed by amphotericin B induces necrotic
      cell death in human hepatocellular carcinoma cells.
AB  - The incidence of liver cancer, the second leading cause of cancer-related deaths
      has increased over the past few decades. Although recent treatments such as
      sorafenib are promising in patients with advanced hepatocellular carcinoma (HCC),
      the response rates remain poor thereby warranting the identification of novel
      therapeutic agents against liver cancer. Herein, we investigated the anti-cancer
      effect of ergosterol (a secondary metabolite in medicinal fungus) pretreatment
      followed by amphotericin B (AmB) treatment on liver cancer cell lines. We
      demonstrated that pretreatment with a nontoxic dose of ergosterol synergistically
      enhanced the cytotoxicity of AmB in both Hep3B and HepJ5 cells. The combination
      treatment-mediated suppression of cancer cell viability occurred through necrosis
      characterized by disrupted cell membrane and significant amounts of debris
      accumulation. In addition, we also observed a concomitant increase in reactive
      oxygen species (ROS) and LC3-II levels in HepJ5 cells treated with ergosterol and
      AmB. Our results suggest that ergosterol-AmB combination treatment effectively
      induced necrotic cell death in cancer cells, and deserves further evaluation for
      development as an anti-cancer agent.

PMID- 29069822
TI  - Alpha lipoic acid attenuates radiation-induced oral mucositis in rats.
AB  - PURPOSE: Radiotherapy is currently one of the main treatment modalities for head
      and neck cancer; however, it also results in severe toxicity to the normal
      tissue, to the detriment of patients. This study aimed to investigate whether
      alpha lipoic acid (ALA) could protect against radiation-induced oral mucositis in
      a rat model. RESULTS: On post-irradiation days 4 and 7, the epithelial layer on
      oral mucosa showed pronounced injury (shortening of the layer) and it is
      diminished by ALA pretreatment before radiation. Hif-1a expression was
      significantly induced in the radiation group on days 4, 7, and 28. GLUT1
      expression was also induced by radiation at all time points, and the expression
      levels peaked on day 28. Phosphorylated p53 level was significantly higher in the
      radiation group on days 4 and 7, and Bax protein expression was significantly
      higher in the same group on day 4 than ALA-pretreated radiation group. TUNEL
      positive staining was significantly lower in the ALA-pretreated radiation group.
      MATERIALS AND METHODS: Rats were assigned to one of the following four groups:
      control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30
      min prior to irradiation, with the neck area including the oral mucosa evenly
      irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear
      accelerator. Rats were sacrificed 4, 7, 28, or 56 days after radiation.
      CONCLUSIONS: The results show that ALA can be used to ameliorate radiation
      induced oral mucositis with head and neck cancer.

PMID- 29069823
TI  - MicroRNA-134 plasma levels before and after treatment with valproic acid for
      epilepsy patients.
AB  - BACKGROUND: Temporal lobe epilepsy is the second most common neurological
      disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital
      role in regulating synaptic plasticity, brain development and post
      transcriptional expression of proteins. In both animal models of epilepsy and
      human patients, miR-134, a brain-specific microRNA has recently been identified
      as a potential regulator of epileptogenesis. METHODS: microRNA identified as
      targets for the actions of valproic acid (VPA) are known to have important
      effects in brain function. In this study, 59 new-onset epilepsy patients and 20
      controls matched by sex and age were enrolled. Patients with a score < 3 were
      allocated into the mild group, 3-5 into the moderate group and >5 into the severe
      group. The plasma miRNA-134 level was quantitatively measured using real-time
      PCR. RESULTS: Plasma miRNA-134 level in new-onset epilepsy patients was
      significantly up-regulated when compared with that in healthy controls, and then
      considerably down-regulated after oral intake of valproic acid medication. The up
      regulated plasma miRNA-134 levels may be directly associated with the
      pathophysiology and severity of epilepsy. CONCLUSION: Plasma miRNA-134 in
      epilepsy may be considered as a potential peripheral biomarker that responds to
      the incidence of epilepsy and associates with use of anti-epilepsy drugs.

PMID- 29069824
TI  - Sensitive detection of PD-L1 expression on circulating epithelial tumor cells
      (CETCs) could be a potential biomarker to select patients for treatment with PD
      1/PD-L1 inhibitors in early and metastatic solid tumors.
AB  - BACKGROUND: The current cancer research strongly focuses on immune therapies,
      where the PD-1, with its ligands plays an important role. It is known that PD-L1
      is frequently up-regulated in a number of different cancers and the relevance of
      this pathway has been extensively studied and therapeutic approaches targeting PD
      1 and PD-L1 have been developed. We used a non-invasive, real-time biopsy for
      determining PD-L1 and PD-L2 expression in CETCs of solid cancer patients.
      METHODS: CETCs were determined from blood of 128 patients suffering from breast
      (72), prostate (27), colorectal (18) and lung (11) cancer. The number of vital
      CETCs and the expression of PD-L1 and PD-L2 were investigated using the
      maintrac(r) method. RESULTS: PD-L1 expressing CETCs were detected in 94.5% of
      breast, 100% of prostate, 95.4% of colorectal and 82% of lung cancer patients
      whereas only 75% of breast cancer patients had PD-L2 positive CETCs. In the PD-L1
      and PD-L2 expressing patients the cell fraction of PD-L1 positive CETCs is
      significantly higher than the fraction of PD-L2 positive CETCs (54.6% vs. 28.7%;
      p<0.001). Breast cancer patients with metastatic disease had significantly more
      PD-L1 positive CETCs as compared to patients without metastasis (median 75% vs.
      61.1%; p<0.05). CONCLUSION: PD-L1 seems to be a major factor in immune evasion
      and is highly expressed on CETCs regardless of the type of cancer. Monitoring the
      frequency of PD-L1 positive CETCs could reflect individual patient's response for
      an anti-PD-1/PD-L1 therapy and may be a promising target of anticancer treatment.

PMID- 29069825
TI  - Mono-ADP-ribosylation of histone 3 at arginine-117 promotes proliferation through
      its interaction with P300.
AB  - Relatively little attention has been paid to ADP-ribosylated modifications of
      histones, especially to mono-ADP-ribosylation. As an increasing number of mono
      ADP-ribosyltransferases have been identified in recent studies, the functions of
      mono-ADP-ribosylated proteins have aroused research interest. In particular,
      histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP
      ribosylated histone have been detected in physiological or pathological
      processes. In this research, arginine-117 (Arg-117; R-117) of hsitone3(H3) is
      identified as the a site of mono-ADP-ribosylation in colon carcinoma(the first
      such site to be identified); this posttranslational modification may promote the
      proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant
      lentivirus transfection and using an activator of P300 allowed us to observe the
      mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up
      regulate the level of acetylated beta-catenin, which could increase the
      expression of c-myc and cyclin D1.

PMID- 29069826
TI  - miR-150 enhances apoptotic and anti-tumor effects of paclitaxel in paclitaxel
      resistant ovarian cancer cells by targeting Notch3.
AB  - Tumor recurrence by obtaining chemoresistance is a major obstacle to treating
      ovarian cancer. By TargetScan database and a luciferase reporter assay, we
      identified miR-150 directly targets Notch3, which is a key oncogene in ovarian
      cancer. We, therefore, investigated the role of miR-150 in ovarian cancer cells,
      and the usefulness of miR-150 as a therapeutic target in chemoresistant ovarian
      cancer, through examining miR-150 expression by qRT-PCR in ovarian cancer cell
      lines and tissues, and assessing the gain-of-function effect by WST, colony
      forming, TUNEL, wound healing and angiogenesis assays. Western blotting was
      performed to evaluate its downstream targets. The miR-150 expression was
      significantly downregulated in ovarian cancers. Treatment with pre-miR-150
      significantly inhibited cancer cell proliferation, and induced apoptosis in PTX
      (paclitaxel) -resistant SKpac cells, which was not seen by PTX only treatment. On
      spheroid forming assay, an additional pre-miR-150 treatment with PTX decreased
      cancer stem cell activation in PTX-resistant SKpac cells. An experimental
      upregulation of miR-150 also decreased cancer cell migration and angiogenesis in
      SKpac cells. The Notch3 downstream proteins(NICD3 and HEY2), and cell cycle
      related proteins (cyclinD3, pS6, and NF-kB), and apoptosis-related proteins (BCL
      2 and BCL-W) were significantly downregulated by pre-miR-150 transfection. Taken
      together, miR-150 is related with PTX-resistance in ovarian cancer, and treatment
      with pre-miR-150 resensitizes cancer cells to PTX. Therefore, it may be a
      promising treatment strategy in chemoresistant and recurrent ovarian cancer.

PMID- 29069827
TI  - The effect of MVK-MMAB variants, their haplotypes and G*E interactions on serum
      lipid levels and the risk of coronary heart disease and ischemic stroke.
AB  - AIM: This study aimed to detect the association of the mevalonate kinase (MVK)
      and methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) gene variants,
      their haplotypes, and gene-environment (G*E) interactions on serum lipid levels
      and the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a
      Chinese Han population. METHODS: Genotyping of the rs3759387, rs7134594, rs877710
      and rs9593 SNPs in 846 CHD and 869 IS patients and 847 healthy controls was
      performed by PCR-RFLP and Sanger sequencing. Logistic regression and factor
      regression were used to investigate the association of 4 MVK-MMAB SNPs and serum
      lipid levels and the risk of CHD and IS. RESULTS: The genotypic and allelic
      frequencies of the rs3759387 and rs7134594 SNPs differed between controls and
      patients (P < 0.0125-0.001). The rs3759387 SNP was associated with the risk of
      CHD and IS in different genetic models. The A-T-G-A and C-T-C-T haplotypes were
      associated with increased risk of CHD. The haplotype of A-T-G-A was associated
      with an increased risk of IS, whereas the C-T-G-A haplotype was associated with a
      decreased risk of IS. Interactions of C-T-C-T-smoking or C-T-C-T-age on the risk
      of CHD, and A-T-G-A-hypertension or A-T-G-A-age on the risk of IS were also
      observed. The subjects with the rs3759387AA genotype in controls had lower high
      density lipoprotein cholesterol (HDL-C) levels than did the subjects with AC/CC
      genotypes. Several SNPs interacted with alcohol consumption and cigarette smoking
      to increase serum HDL-C and apolipoprotein A1 levels, but they interacted with
      body mass index >= 24 kg/m2 to decrease serum HDL-C and apolipoprotein A1 levels.
      CONCLUSION: Several MVK-MMAB variants, especially the rs3759387 SNP, 4 main
      haplotypes, and G*E interactions were associated with serum lipid levels and the
      risk of CHD and IS in a Chinese Han population.

PMID- 29069828
TI  - Neutrophils protect lymphoma cells against cytotoxic and targeted therapies
      through CD11b/ICAM-1 binding.
AB  - Innate immune cells constitute a substantial proportion of the cells within the
      tumor microenvironment. Besides the contribution of the microenvironment to tumor
      proliferation and survival, there is direct evidence that interactions between
      tumor cells and their microenvironment alter sensitivity to anti-cancer agents.
      Neutrophils, a key player in the innate immune system, have been less studied
      than many other immune cells regarding their impact on cancer cell response to
      anti-cancer agents. In our 2D and 3D coculture systems, human neutrophils and
      differentiated HL60 cells attenuated the sensitivity of various lymphoma cell
      lines to several anti-cancer agents, including targeted therapies. Neutrophil
      induced protection was dependent on cell-cell interaction between CD11b and ICAM
      1 expressed by neutrophils and B cells, respectively and was shown to be Mcl-1
      dependent. The protective effect of neutrophils was validated in vivo using
      immune-compromised mice inoculated with human NHL with our without neutrophils
      then followed by treatment with chemotherapy. Similar findings were made on
      primary cells purified from patients with chronic lymphocytic leukemia, treated
      with fludarabine or targeted agents in the presence of autologous neutrophils. In
      a clinical study, patients with non-Hodgkin's lymphoma with increased neutrophil
      counts displayed a reduced response rate to therapy. These findings reveal a
      novel protective mechanism of neoplastic B cells involving innate immune cells
      which could be pharmacologically targeted to enhance the antitumor effect of
      therapy.

PMID- 29069829
TI  - The miR-486-5p plays a causative role in prostate cancer through negative
      regulation of multiple tumor suppressor pathways.
AB  - MicroRNAs have been broadly implicated in cancer, but their exact function and
      mechanism in carcinogenesis remain poorly understood. Aberrant miR-486-5p
      expression is frequently found in human cancers. Here we showed a significant
      overexpression of miR-486-5p in prostate cancer compared with that in normal
      tissue and cells, and we proposed that altered expression of miR-486-5p in the
      prostate contributed to prostate cancer. Firstly, miR-486-5p inhibition
      expression reduced prostate cancercell proliferation, migration, and colonization
      in vitro and prostate tumor development in vivo. Moreover, we integrated RNA
      sequencing and target genes prediction, and systemically identified miR-486-5p
      candidate target genes. We conducted an experiment verifying that miR-486-5p
      drives tumorigenesis by directly targeting multiple negative regulators, which
      were involved in PTEN/PI3K/Akt, FOXO, and TGF-b/Smad2 signaling. Finally, we
      demonstrated that hypoxia-inducible factor-1a and TCF-12 are located at the miR
      486-5p promoter, which stimulates the transcription of miR-486-5p itself.
      Collectively, our findings unveil miR-486-5p as a powerful prostate cancer driver
      that coordinates the activation of multiple oncogenic pathways and demonstrates
      some stimulators, which mediate the miR-486-5p signaling pathway and may be
      targeted for therapy.

PMID- 29069831
TI  - Stereotactic ablative body radiotherapy for spinal metastasis from hepatocellular
      carcinoma: its oncologic outcomes and risk of vertebral compression fracture.
AB  - Spinal metastases from hepatocellular carcinoma (HCC) require high-dose
      irradiation for durable pain and tumor control. Stereotactic ablative body
      radiotherapy (SABR) enables the delivery of high-dose radiation. However, but
      vertebral compression fracture (VCF) can be problematic. The aim of his study is
      to evaluate the outcome and risk of VCF after SABR for spinal metastasis from
      HCC. We retrospectively reviewed 33 lesions in 42 spinal segments from 29
      patients who received SABR with 1 fraction (16-20 Gy), or 3 fractions (18-45 Gy)
      from September 2009 to January 2015. The 1-year local control (LC) rate was
      68.3%. Radiographic grade of cord compression (RGCC) was the only independent
      prognostic factor associated with LC (P = 0.007). The 1-year ultimate LC rate
      including the outcome of salvage re-irradiation was 87.2%. The pain response rate
      was 73.3% according to the categories of the International Bone Metastases
      Consensus Group. The 1-year VCF-free rate was 71.5%. Pre-existing VCF (P < 0.001)
      and only-lytic change (P = 0.017) were associated with a higher post-SABR VCF
      rate. One-third of post-SABR VCFs required interventions. SABR for spinal
      metastases from HCC provided efficacious LC, especially for lesions with RGCC <=
      II, and showed effective and durable pain relief. As VCF after SABR occurred
      frequently for vertebral segments with pre-existing VCF and only-lytic change,
      early preventive vertebroplasty is considerable for those high-risk vertebral
      segments.

PMID- 29069830
TI  - Protein-coding genes, long non-coding RNAs combined with microRNAs as a novel
      clinical multi-dimension transcriptome signature to predict prognosis in ovarian
      cancer.
AB  - Ovarian cancer is prevalent in women which is usually diagnosed at an advanced
      stage with a high mortality rate. The aim of this study is to investigate protein
      coding gene, long non-coding RNA, and microRNA associated with the prognosis of
      patients with ovarian serous carcinoma by mining data from TCGA (The Cancer
      Genome Atlas) public database. The clinical data of ovarian serous carcinoma
      patients was downloaded from TCGA database in September, 2016. The mean age and
      survival time of 407 patients with ovarian serous carcinoma were 59.71 +/- 11.54
      years and 32.98 +/- 26.66 months. Cox's proportional hazards regression analysis
      was conducted to analyze genes that were significantly associated with the
      survival of ovarian serous carcinoma patients in the training group. Using the
      random survival forest algorithm, Kaplan-Meier and ROC analysis, we kept
      prognostic genes to construct the multi-dimensional transcriptome signature with
      max area under ROC curve (AUC) (0.69 in the training group and 0.62 in the test
      group). The selected signature composed by VAT1L, CALR, LINC01456, RP11-484L8.1,
      MIR196A1 and MIR148A, separated the training group patients into high-risk or low
      risk subgroup with significantly different survival time (median survival: 35.3
      months vs. 64.9 months, P < 0.001). The signature was validated in the test group
      showing similar prognostic values (median survival: 41.6 months in high-risk vs.
      57.4 months in low-risk group, P=0.018). Chi-square test and multivariable Cox
      regression analysis showed that the signature was an independent prognostic
      factor for patients with ovarian serous carcinoma. Finally, we validated the
      expression of the genes experimentally.

PMID- 29069832
TI  - Acylated and unacylated ghrelin inhibit atrophy in myotubes co-cultured with
      colon carcinoma cells.
AB  - Cancer cachexia is a result of increased protein degradation and decreased
      protein synthesis. The multifunctional circulating hormone ghrelin promotes
      synthesis and inhibits degradation of muscle protein, but its mechanism of action
      is not fully understood. Here, we investigated whether co-culturing C2C12
      myotubes with CT26 colon carcinoma cells induces myotube atrophy, and whether
      acylated ghrelin (AG) and unacylated ghrelin (UnAG) had anti-atrophic effects. We
      found that co-culture induced myotube atrophy and increased tumor necrosis factor
      alpha (TNF-alpha) and myostatin concentrations in the culture medium. Moreover,
      co-culture down-regulated myogenin and MyoD expression, inhibited the Akt
      signaling, up-regulated ubiquitin E3 ligase expression, and activated the calpain
      system and autophagy in myotubes. Both AG and UnAG inhibited these changes. Our
      study describes a novel in vitro model that can be employed to investigate cancer
      cachexia, and our findings suggest a possible use for AG and UnAG in treating
      cancer cachexia.

PMID- 29069833
TI  - Differential expression of microRNA let-7b-5p regulates burn-induced
      hyperglycemia.
AB  - One of the classical features observed in patients with burn injury is
      hyperglycemia. There have been previous reports that a cohort of microRNAs
      (miRNAs) is differentially expressed in the dermis of patients with burn injury.
      More specifically, it has been shown that the miR-194 can target the insulin-like
      growth factor receptor 1 (IGF1R) and silence its protein expression resulting in
      hyperglycemia. The objective of the current study was to discover if additional
      miRNA-mediated post-transcriptional mechanism exists that lead to suppression of
      IGF1R protein expression post-burn injury. Using the 30% total body surface area
      (TBSA) model of burn injury in rats we found that the miRNA let-7b can target
      IGF1R and downregulate its protein expression, in turn attenuating PI3K/Akt and
      Gsk3beta activation leading to hyperglycemia. Increased let-7b expression was
      significantly more than the previously reported miR-194 both in the burn rats
      compared to sham and in patients with burn injury compared to healthy subjects.
      Serum from burn rats also resulted in decreased IGF1R protein expression in rat
      L6 myotubes. In vivo targeting of let-7b by antagomir mitigated the effect of
      increased let-7b expression on IGF1R protein expression and hyperglycemia. Thus
      targeting let-7b might be a promising approach to treat hyperglycemia in patients
      with burn injury.

PMID- 29069834
TI  - PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN
      phosphorylation.
AB  - Phosphorylation is a recently established cause of phosphatase and tensin homolog
      (PTEN) gene inactivation, which leads to defect tumour-suppressor function. In
      pancreatic cancer, this phenomenon has not been reported. Based on database and
      clinical sample analyses, we found that PTEN phosphorylation occurs in pancreatic
      ductal adenocarcinoma patient tissues and cell lines, and we aimed to find a
      method for dephosphorylation. PDZ-containing 1 (PDZK1), a tumour-associated
      protein that shares its PDZ-binding sequence with the carboxyl-terminal domain of
      PTEN, was significantly down-regulated in pancreatic cancer as compared to
      adjacent non-tumour tissues. In vitro, PDZK1 overexpression reversed the
      proliferation and migration abilities of pancreatic cancer cells and led to
      significantly decreased PTEN phosphorylation and AKT phosphorylation by
      interacting with wild-type PTEN. In addition, a transcription factor-activation
      assay supported that PDZK1 overexpression enhanced the anti-oncogene function of
      PTEN by regulating the activities of its downstream transcription factors,
      including p53, NF-kappaB, and FOXO1. In vivo, nude mice stably over-expressing
      PDZK1 had lower tumour weights and volumes and showed significantly down
      regulated PTEN phosphorylation in xenograft tumour tissues as compared to the
      control group. Moreover, low PDZK1 expression strongly correlated with advanced
      stage and poor prognosis of patients with pancreatic ductal adenocarcinoma. In
      conclusion, our study elucidated the tumour-suppressor role of PDZK1 in
      pancreatic cancer through down-regulating PTEN phosphorylation, and established
      PDZK1 as a potential novel prognostic marker for pancreatic cancer.

PMID- 29069836
TI  - Genetic analysis of the Vitamin D receptor start codon polymorphism (FokI) in
      cervical vertebra and lumbar spine pathologies: a meta-analysis.
AB  - BACKGROUND: Vitamin D receptor (VDR) FokI polymorphism has been reported to
      influence the risk of spinal diseases. However, several studies suggest
      inconsistent results. Therefore, we performed this analysis to reveal the
      accurate relationship between VDR FokI polymorphism and spinal diseases.
      MATERIALS AND METHODS: 8 articles accord with the strict inclusion and exclusion
      criteria. 1116 cases and 1263 controls are entered into this analysis. The pooled
      odds ratios (ORs) and 95% confidence intervals (CI) are calculated to evaluate
      the association between VDR gene polymorphism and spinal diseases. RESULT: The
      results suggest that allele F is a risk factor for spinal diseases and the
      difference is significant (F vs. f: OR = 1.151, 95% CI, 1.020-1.300). For the
      genotype analysis of VDR FokI, no statistical differences exist in the models of
      heterozygote comparison (Ff vs. ff), homozygote comparison (FF vs. ff) and
      dominant model (FF + Ff vs. ff) (p > 0.05). However, in recessive model (FF vs.
      Ff + ff), there is a significant association between VDR polymorphism and spinal
      diseases (OR = 1.209, 95% CI, 1.017-1.436). In subgroup analysis, the results
      show that allele F is a risk factor for spinal diseases in each estimation. In
      hospital-based subgroup, the significant differences exist in FF vs. ff and FF
      vs. Ff + FF models. In degenerative spine diseases group, the results are
      consistent with that of overall studies. CONCLUSIONS: According to results of
      this meta-analysis, allele F is associated with the increased risk of spinal
      diseases. FF genotype may contribute to the susceptibility of spinal diseases.
      Therefore, VDR FokI polymorphism is related with spinal diseases.

PMID- 29069835
TI  - 5-HT induces PPAR gamma reduction and proliferation of pulmonary artery smooth
      muscle cells via modulating GSK-3beta/beta-catenin pathway.
AB  - Studies have shown that peroxisome proliferator-activated receptor gamma (PPAR
      gamma) is down-regulated in pulmonary vascular lesions of patients with pulmonary
      hypertension (PH) and animal models of PH. Yet, the detailed molecular mechanisms
      underlying this alteration are not fully defined; the aim of this study is to
      address this issue. 5-HT dose- and time-dependently reduced PPAR gamma expression
      and promoted pulmonary artery smooth muscle cells (PASMCs) proliferation; this
      was accompanied with the phosphorylation of Akt, inactivation of GSK-3beta and up
      regulation of beta-catenin. Importantly, pre-treatment of cells with PI3K
      inhibitor (Ly294002) or prior silencing of beta-catenin with siRNA blocked 5-HT
      induced PPAR gamma reduction and PASMCs proliferation. In addition, inactivation
      or lack of GSK-3beta or inhibition of proteasome function up-regulated beta
      catenin protein without affecting its mRNA level and reduced PPAR gamma protein
      expression. Taken together, our study indicates that 5-HT suppresses PPAR gamma
      expression and stimulates PASMCs proliferation by modulating GSK-3beta/beta
      catenin axis, and suggests that targeting this pathway might have potential value
      in the management of PH.

PMID- 29069837
TI  - The MMP2 rs243865 polymorphism increases the risk of prostate cancer: A meta
      analysis.
AB  - : Prostate cancer is a common cancer in men. However, the association between the
      rs243865 single-nucleotide polymorphisms in the matrix metalloproteinase 2 gene
      (MMP2) and the risk for prostate cancer is inconclusive. We searched the PubMed,
      EMBASE, Cochrane Library, and the Chinese CNKI and WANFANG databases for the
      relevant literature. Data were extracted and pooled results were estimated from
      odds ratios (OR) with 95% confidence intervals (95% CIs). The quality of included
      studies was assessed, and publication bias of all included studies was examined.
      A total five studies involving 1895 patients with prostate cancer and 1918
      controls were included. There was a significant association between rs243865
      polymorphisms and higher risk of prostate cancer in the co-dominant model,
      dominant model, and allele model (CC vs. CT+TT, OR: 1.60, 95% CI: 1.22-2.11, P =
      0.001; CC vs. CT, OR: 1.80, 95% CI: 1.34-2.42, P < 0.001; C vs. T, OR: 1.32, 95%
      CI: 1.05-1.66, P = 0.016, respectively). However, there was no significant
      difference between the co-recessive model and recessive model. Our meta-analysis
      results suggest that MMP2 rs243865 polymorphisms are significantly associated
      with higher risk of prostate cancer.

PMID- 29069838
TI  - GSTP1 polymorphism predicts treatment outcome and toxicities for breast cancer.
AB  - This study aimed to investigate the association of the GSTP1 gene polymorphism
      with the outcomes and toxicities of treatments in breast cancer. Odds ratios
      (ORs) and 95% confidence intervals (95% CIs) were calculated for the association
      of GSTP1 polymorphism with tumour response and toxicities, and the hazard ratios
      (HRs) and 95% CIs were calculated for the association between GSTP1 polymorphism
      and overall survival (OS). The statistical analysis showed that the GSTP1
      polymorphism was not associated with tumour response or OS. A significant
      increase in the incidence of toxicities was observed (GA vs. AA OR = 1.45, 95% CI
      = 1.04-2.01, P = 0.028; GG vs. AA OR = 1.47, 95% CI = 1.03-2.10, P = 0.036;
      recessive model OR = 1.54, 95% CI = 1.13-2.09, P = 0.006; and allele model OR =
      1.35, 95% CI = 1.07-1.71, P = 0.011), especially in the chemotherapy +/- surgery
      group (GA vs. AA OR = 1.64, 95% CI = 1.05-2.56, P = 0.030; recessive model OR =
      1.72, 95% CI = 1.17-2.54, P = 0.006; and allele model OR = 1.57, 95% CI = 1.11
      2.21, P = 0.010). Our results indicate that the GSTP1 polymorphism may be
      associated with increased toxicity, especially in patients treated with
      chemotherapy +/- surgery.

PMID- 29069839
TI  - Role of nab-paclitaxel in metastatic breast cancer: a meta-analysis of randomized
      clinical trials.
AB  - Whether nab-paclitaxel and conventional taxanes are equally effective for
      metastatic breast cancer (MBC) remains unclear. We conducted meta-analysis of
      trials that compared nab-paclitaxel-based chemotherapy with solvent-based
      paclitaxel (sb-paclitaxel) and docetaxel-based chemotherapy. A literature search
      was performed to identify articles that compared nab-paclitaxel-based
      chemotherapy with sb-paclitaxel or docetaxel-based chemotherapy for MBC. Four
      randomized controlled trials (1,506 patients) were identified from 1,268 reports.
      We detected equivalent overall response, overall survival, and survival
      probability (one-year, two-year). Grade 3 to 4 hematological and non
      hematological toxicities were also comparable except that sensory neuropathy was
      more prominent for nab-paclitaxel-based chemotherapy (16.9% vs. 10%, odds ratio =
      1.89, 95% confidence interval = 1.36-2.61, P < 0.001). No significant publication
      bias was detected. Consistent results stratified by treatment arm, study phase,
      treatment line, and study location were observed, except that overall response
      rate to nab-paclitaxel-based chemotherapy was significantly higher in the
      subgroup of randomized phase II trials, non-first-line treatment, and East Asian
      population. This meta-analysis failed to demonstrate advantages of nab-paclitaxel
      compared with sb-paclitaxel and docetaxel in patients with MBC. The newer agent
      was associated with increased sensory neuropathy, equivalent survival, and
      possibly increased overall response for some specific patients.

PMID- 29069840
TI  - Meta-analysis reveals gender difference in the association of liver cancer
      incidence and excess BMI.
AB  - Excess body weight has a positive association with risk of liver cancer, but the
      gender difference in the relationship between body mass index and liver cancer
      risk remains uncertainty. In this work, we performed meta-analysis for excess
      body weight and risk of liver cancer incidence to identify the gender difference.
      We searched the English-languages database and the Chinese literature databases
      to May 12, 2017. Overall, a total of 17 studies were included. Relative risks
      (RRs) with 95% confidence intervals was used to evaluate the strength of these
      associations. The RRs of liver cancer incidence for obese men and women were 2.04
      (1.70-2.44) and 1.56 (1.37-1.78). The former one was significantly higher than
      the later one (P for interaction = 0.02). Notably, the RR of liver cancer
      incidence in non-Asian obese men was even higher than their counter part
      (2.31(1.85-2.91) vs. 1.56 (1.31-1.86), P for interaction = 0.01). Similar gender
      difference was observed in the dose-response curve. As example, at the point of
      BMI = 32 kg/m2, the RRs for men and women were 1.61 (1.45-1.79) and 1.41 (1.02
      1.94) respectively. Findings from this meta-analysis indicate that obesity is
      associated with a higher risk of liver cancer incidence in men, especially in non
      Asian men, which might partially contribute to the male dominance of liver cancer
      incidence.

PMID- 29069841
TI  - Impact of hyperlipidemia and atrial fibrillation on the efficacy of endovascular
      treatment for acute ischemic stroke: a meta-analysis.
AB  - INTRODUCTION: Stroke is the crucial cause of death annually. Inconsistent results
      from the randomized controlled trials (RCTs) aroused controversy on efficacy of
      endovascular treatment (EVT). MATERIALS AND METHODS: To evaluate the efficacy of
      EVT in stroke patients. We searched three databases including PubMed, Web of
      science and the Cochrane Library from Jan 2011 to Apr 2017. Eligible studies were
      RCTs comparing EVT versus standard medical therapy alone. The primary outcomes
      were favorable functional outcomes (modified Rankin Scale score, 0-2) at 3
      months. Meta regression analysis and subgroup analysis were used to explore
      potential influence factors responsible for the effectiveness of EVT. RESULTS:
      Eleven RCTs involving 3018 patients were included in our study. EVT showed better
      functional outcomes at 90 days (OR, 1.71; 95% CI, 1.28-2.28; P < 0.001) and a
      higher recanalization rate at 24h (OR, 6.49; 95% CI, 4.79-8.79; P < 0.001). In
      meta-regression and subgroup analysis, primary outcomes were significantly better
      among patients with atrial fibrillation (Adj R-squared 46.30%, P = 0.054; OR,
      2.40; 95% CI, 1.81-3.19; P < 0.001), patients without hyperlipidemia (Adj R
      squared 35.21%, P = 0.159; OR, 2.34; 95% CI, 1.80-3.04; P < 0.001) and when new
      generation thrombectomy device was used (Adj R-squared 72.21%, P = 0.011; OR,
      2.14; 95% CI, 1.75-2.61; P < 0.001). CONCLUSIONS: EVT showed superior clinical
      outcomes compared with standard medical therapy. The rate of using new generation
      thrombectomy device was the critical factor influencing therapeutic outcome.
      Hyperlipidemia and atrial fibrillation may also cause the potential effect.

PMID- 29069842
TI  - The diagnostic value of serum creatinine and cystatin c in evaluating glomerular
      filtration rate in patients with chronic kidney disease: a systematic literature
      review and meta-analysis.
AB  - BACKGROUND: Serum biomarkers, such as serum creatinine (SCr) and serum cystatin C
      (SCysC), have been widely used to evaluate renal function in patients who have
      chronic kidney disease (CKD). OBJECTIVE: This article aims to assess the value of
      determining SCr and SCysC levels in patients that have long-term kidney disease.
      Approaches: MEDLINE, EmBase, the Cochrane Library and other databases were
      searched using both MeSH terms and text words to collect research that assessed
      the diagnostic value of using SCr and SCysC to evaluate Glomerular Filtration
      Rate (GFR) in patients with CKD. Data were converted into fourfold tables.
      Summary Receiver Operating Characteristic Curves and meta-analyses were
      accomplished via Meta-Disc version 1.4. RESULTS: In total, 21 relevant articles
      involving 3112 study subjects were included in our review. Results showed that
      the collective sensitivity for SCr and SCysC was 0.77 (95% CI: 0.69-0.84) and
      0.87 (95% CI: 0.82-0.91), respectively. The pooled specificity for SCr and SCysC
      was 0.91 (95% CI: 0.86-0.94) and 0.87 (95% CI: 0.82-0.91), respectively. Subgroup
      analyses demonstrated that when GFR cut-off values are set to 60 (ml/min/1.73
      m2), the pooled sensitivity is 0.94 (95% CI: 0.90-0.96) for SCysC and 0.75 (95%
      CI: 0.68-0.82) for SCr. CONCLUSIONS: The diagnostical accuracy for impaired
      kidney function favors SCysC. Confidence intervals for the pooled sensitivity and
      specificity for SCr and SCysC overlap. However, SCysC is more sensitive for
      estimating GFR than SCr when GFR cut-off values are set to 60 (ml/min/1.73 m2).

PMID- 29069843
TI  - Statins reduce all-cause mortality in chronic obstructive pulmonary disease: an
      updated systematic review and meta-analysis of observational studies.
AB  - Recently, a number of observational studies have suggested that use of statins
      reduces mortality in patients suffering from chronic obstructive pulmonary
      disease (COPD). To obtain a more valid assessment, we update the meta-analysis of
      the effect of statins on COPD exacerbation and mortality. We searched for
      eligible articles using PubMed, Medline, Embase, the Cochrane Central Register of
      Controlled Trials, Cochrane Databases and Web of Science between January 2006 and
      February 2017, with no restrictions. The hazard ratio (HR) with 95% confidence
      interval (CI) was estimated. Publication bias was evaluated by funnel plot and
      Begg's test. Sensitivity analyses were also conducted. Twenty studies with a
      total of 303,981 patients were included. Thirteen articles provided data on all
      cause mortality (165,221 participants), and the pooled hazard ratio of 0.65 (95%
      CI: 0.57-0.74, P < 0.001). Nine cohorts involving 155,435 patients reported data
      for COPD exacerbation with or without hospitalization, and they gave a HR of
      0.58(95%CI: 0.48-0.72, P < 0.001). Our systematic review of exclusively
      observational studies showed a clear benefit of statins for patients suffering
      from COPD.

PMID- 29069844
TI  - The addition of bevacizumab in the first-line treatment for metastatic colorectal
      cancer: an updated meta-analysis of randomized trials.
AB  - Bevacizumab has shown survival benefits when added to chemotherapy in patients
      with metastatic colon cancer (mCRC). However, the efficacy of bevacizumab may
      depend on the accompanying chemotherapeutic regimen. We performed this meta
      analysis to examine the impact of the choice of chemotherapy regimen on the
      survival benefits of bevacizumab in the first-line treatment for patients with
      mCRC. Electric databases were searched for eligible randomized trials. From 9
      studies, 3,710 patients with mCRC were included in the meta-analysis of hazard
      ratios (HRs) for progression-free survival (PFS) or overall survival (OS).
      Compared with chemotherapy alone, the addition of bevacizumab to chemotherapy
      significantly prolonged PFS (HR = 0.66 [95% confidence interval (CI), 0.55-0.77],
      P < 0.0001) and OS (HR = 0.84 [95% CI, 0.77-0.92], P = 0.0001). In the subgroup
      analysis according to the chemotherapeutic regimens, bevacizumab showed both PFS
      (HR = 0.57 [95% CI, 0.41-0.77], P = 0.0004) and OS (HR = 0.79 [95% CI, 0.67
      0.93], P = 0.004) advantages only in combination with irinotecan-based regimen.
      In conclusion, this meta-analysis confirms that the addition of bevacizumab to
      chemotherapy significantly prolongs PFS and OS in the first-line treatment for
      mCRC. The subgroup analyses suggest that irinotecan-based regimen may be a better
      partner of bevacizumab in terms of both PFS and OS.

PMID- 29069845
TI  - The meta and bioinformatics analysis of GRP78 expression in gastric cancer.
AB  - GRP78 is a molecular chaperone located in endoplasmic reticulum, and induces
      folding and assembly of newly-synthesized proteins, proteasome degradation of
      aberrant proteins, and translocation of secretory proteins, autophagy, and
      epithelial-mesenchymal transition. We performed a systematic meta- and
      bioinformatics analysis through multiple online databases up to March 14, 2017.
      It was found that up-regulated GRP78 expression in gastric cancer, compared with
      normal mucosa at both protein and mRNA levels (p < 0.05). GRP78 expression was
      positively correlated with depth of invasion, TNM staging and dedifferentiation
      of gastric cancer (p < 0.05), while its mRNA expression was negatively correlated
      with depth of invasion, histological grading and dedifferentiation (p < 0.05). A
      positive association between GRP78 expression and unfavorable overall survival
      was found in patients with gastric cancer (p < 0.005). A higher GRP78 mRNA
      expression was positively correlated with overall and progression-free survival
      rates of all cancer patients, even stratified by aggressive parameters, or as an
      independent factor (p < 0.05). These findings indicated that GRP78 expression
      might be employed as a potential marker to indicate gastric carcinogenesis and
      subsequent progression, even prognosis.

PMID- 29069846
TI  - Expression of the long non-coding RNA HOTAIR as a prognostic factor in squamous
      cell carcinoma of the head and neck: a systematic review and meta-analysis.
AB  - INTRODUCTION: Long noncoding RNAs (lncRNAs) are often dysregulated in cancer
      tissue and seem to play an important role in neoplastic processes. Recent studies
      have shown that the HOX transcript antisense intergenic RNA (HOTAIR) may play a
      role as a marker of prognosis in squamous cell carcinoma of the head and neck
      (SCCHN). The aim of this study was to perform a meta-analysis of studies focused
      on the prognostic role of HOTAIR in SCCHN. RESULTS: At the end of the selection
      process, four studies were considered eligible for inclusion in the meta
      analysis, comprising a total of 271 patients. Meta-analysis revealed that high
      expression of HOTAIR was associated with poor overall survival (HR, 1.90; 95% CI:
      [1.42, 2.53]; p < 0,0001), advanced tumor stage (OR, 3.44; 95% CI: [1.84, 6.43];
      p < 0,001) and lymph-node metastasis (OR, 3.31; 95% CI: [1.24, 8.79]; p = 0,02).
      MATERIALS AND METHODS: The literature search was performed in the following
      databases: PUBMED, SCOPUS, EMBASE and Web of Science, in order to find studies
      that met the inclusion criteria. CONCLUSIONS: Findings from this systematic
      review and meta-analysis revealed that HOTAIR represents a potential biomarker of
      prognosis in patients with squamous cell carcinoma of the head and neck.

PMID- 29069847
TI  - The effect of pathological fractures on the prognosis of patients with
      osteosarcoma: a meta-analysis of 14 studies.
AB  - Osteosarcoma is a leading cause of malignant tumor related death. We conducted a
      meta-analysis to evaluate the association between pathological fractures and
      prognosis in patients with osteosarcoma. We searched PubMed, Web of Science, and
      Embase for studies published until May 15, 2017. Crude and adjusted relative risk
      (RR) with 95% confidence intervals were used to compare data between the case and
      control groups. Fourteen studies and 3910 patients were included in the final
      meta-analysis. No statistically significant difference was detected between the
      pathological fracture and non-pathological fracture groups in local recurrences
      analysis (RR = 1.102, 95% CI: 0.813-1.495, P = 0.531); however, a statistically
      significant difference was found between group in distant metastasis (RR = 1.424,
      95% CI: 1.089-1.862, P = 0.01). For survival rates, the following RRs were
      calculated: 3-year overall survival (OS) (RR = 0.736, 95% CI: 0.593-0.912, P =
      0.005); 5-year OS (RR = 0.889, 95% CI: 0.791-0.999, P = 0.049); 3-year event-free
      survival (EFS) (RR = 0.812, 95% CI: 0.682-0.966, P = 0.018); and 5-year EFS (RR =
      0.876, 95% CI: 0.785-0.978, P = 0.019). The pooled estimate of RR was 0.673 (95%
      CI: 0.364-1.244, P = 0.206) for local recurrence in the amputation and limb
      salvage groups. In conclusion, our analysis indicated that there were no
      differences in local recurrence and local recurrence after limb salvage between
      patients with or without a fracture. Additionally, the patients with pathological
      fracture had a higher risk of distant metastasis and lower 3-year OS, 5-year OS,
      3-year EFS, and 5-year EFS. Considering the limitations of this study, we believe
      that future large-scale studies should be performed to confirm our conclusions.

PMID- 29069848
TI  - Efficacy and safety of immunosuppressive medications for steroid-resistant
      nephrotic syndrome in children: a systematic review and network meta-analysis.
AB  - BACKGROUND: Conventional meta-analyses and randomized controlled trials have
      shown inconsistent results regarding the efficacy of immunosuppressants for
      pediatric steroid-resistant nephrotic syndrome (SRNS). OBJECTIVE: To conduct a
      network meta-analysis aimed at evaluating the efficacy and safety of available
      immunosuppressive agents in pediatric patients with SRNS. STUDY METHODS: MEDLINE,
      the Cochrane Central Register of Controlled Trials, and EMBASE were searched on
      January 2017. Data from randomized controlled trials (RCTs) were included. The
      main outcomes analyzed were efficacy [number/portion with complete remission
      (CR), number/portion with partial remission (PR), and total number/portion in
      remission (TR)] and safety [adverse secondary event (ASE) rates]. RESULTS: A meta
      analysis of 18 RCTs showed that tacrolimus was more efficacious for achieving CR
      than intravenous (i.v.) cyclophosphamide, mycophenolate mofetil (MMF), oral
      cyclophosphamide, leflunomide, chlorambucil, azathioprine, and
      plaebo/nontreatment (P/NT), and more efficacious than i.v. cyclophosphamide, oral
      cyclophosphamide, and P/NT in terms of TR outcomes. Cyclosporin was associated
      with a greater CR rate than i.v. cyclophosphamide, MMF, oral cyclophosphamide,
      chlorambucil, azathioprine, or P/NT, and associated with a greater TR rate than
      i.v. cyclophosphamide, oral cyclophosphamide, or P/NT. MMF was found to be more
      efficacious than i.v. cyclophosphamide and oral cyclophosphamide in terms of TR.
      CONCLUSIONS: Tacrolimus and cyclosporine may be preferred initial treatments for
      children with SRNS. MMF may be another option for this patient population.
      Further studies of the efficacy and safety of these three drugs in children with
      SRNS should be pursued.

PMID- 29069849
TI  - Association of four genetic polymorphisms in the vascular endothelial growth
      factor-A gene and development of ovarian cancer: a meta-analysis.
AB  - This study meta-analyzed the literature on possible association of four
      polymorphisms (+936C/T, -460C/T, -2578C/A and -1154G/A) in the vascular
      endothelial growth factor (VEGF)-A gene with risk of ovarian cancer. Meta
      analysis of 7 case-control studies involving +936C/T, 4 studies involving 
      460C/T, 4 studies involving -2578C/A and 2 studies involving -1154G/A showed
      significant association between -460C/T and ovarian cancer risk. This risk was
      observed in the total population (allelic model, OR 1.80, 95% CI 1.26-2.59, P =
      0.001; recessive model, OR 1.84, 95% CI 1.13-2.98, P = 0.01; dominant model, OR
      0.51, 95% CI 0.39-0.67, P < 0.001; homozygous model, OR 2.48, 95% CI 1.72-3.56, P
      < 0.001; heterozygous model, OR 1.67, 95% CI 1.26-2.21, P < 0.001) and in the
      subgroup of Asian study participants. The CA genotype at -2578C/A was a risk
      factor in the total population, while the CT genotype at +936C/T was a protective
      factor in Caucasians. None of the five genetic models suggested a significant
      association between -1154G/A and ovarian cancer risk in the entire study
      population, or between +936C/T and risk in Asian or Chinese participants. These
      findings should be verified in large, well-designed studies.

PMID- 29069850
TI  - Metformin use and survival outcomes in endometrial cancer: a systematic review
      and meta-analysis.
AB  - Previous studies have evaluated the effects of metformin use on survival outcomes
      in endometrial cancer, but their results are inconsistent. We conducted a
      systematic review and meta-analysis to provide a quantitative assessment of the
      drug's effects based on available evidence. We searched PubMed, Embase, and the
      Cochrane Central Register of Controlled Trials to identify relevant studies that
      evaluated the association between metformin use on survival outcomes in
      endometrial cancer. Pooled hazard ratios (HRs) with 95% confidence intervals
      (CIs) were calculated to evaluate the association of metformin use with overall
      survival and with progression-free survival using a fixed-effects model. A total
      of nine studies involving 2,016 patients with endometrial cancer were identified.
      In a meta-analysis of eight studies involving 1,594 individuals, metformin use
      was associated with significant improvements in overall survival (HR, 0.51; 95%
      CI, 0.41 to 0.64). Metformin users similarly showed improved progression-free
      survival in a meta-analysis of two studies involving 632 individuals (HR, 0.63;
      95% CI, 0.46 to 0.87). In conclusion, endometrial cancer patients who use
      metformin show improved overall survival and progression-free survival. Further
      studies are required to confirm the full potential effects of metformin use on
      survival outcomes in endometrial cancer.

PMID- 29069851
TI  - Discrepancies on the association between androgen deprivation therapy for
      prostate cancer and subsequent dementia: meta-analysis and meta-regression.
AB  - Limited literature exists on the association between androgen deprivation therapy
      (ADT) for prostate cancer (PCa) and subsequent dementia and the study conclusions
      are in conflicts with one another. We searched several cohort databases from 1960
      to 2017 for observational or prospective studies that reported on an association
      between ADT for PCa and subsequent dementia. A meta-analysis was performed to
      cumulatively determine the association between ADT and dementia including
      Alzheimer's disease using an incidence rate ratio (IRR), crude hazard ratio (HR),
      and adjusted HR. Seven studies were eligible for the meta-analysis, with the
      inclusion of a total of 90, 543 prostate cancer patients. The pooled overall IRR,
      crude HR, and adjusted HR were 1.78 [95% confidence interval (CI): 1.51-2.10)],
      1.80 (95% CI: 1.05-3.10), and 1.59 (95% CI: 1.16-2.18), respectively. A meta
      regression analysis showed that the crude HR was affected by both follow -up
      duration and lag time in the univariate model (p = < 0.001). However, IRR and
      adjusted HR were not affected by these moderators. The overall outcomes of IRR,
      crude HR, and adjusted HR were found to be balanced in the sensitivity analysis.
      A positive association was demonstrated between ADT and the subsequent incidence
      of dementia in this meta-analysis. Methodological difference including follow-up
      duration and the time lag could be related with the discrepancies.

PMID- 29069852
TI  - Prognostic value of c-Met overexpression in pancreatic adenocarcinoma: a meta
      analysis.
AB  - The overexpression of c-Met protein has been detected in pancreatic
      adenocarcinoma (PAC). However, its prognostic impact remains unclear. We
      performed this meta-analysis to evaluate the prognostic value of c-Met
      overexpression in PAC. A systematic computerized search of the electronic
      databases such as PubMed, Embase, and Google Scholar was carried out. From 5
      studies, 423 patients who underwent surgical resection for PAC were included in
      the meta-analysis. Compared with patients with PAC showing low c-Met expression,
      patients with c-Met-high tumor had significantly worse disease-free survival
      (hazard ratio = 1.94 [95% confidence interval, 1.46-2.56], P = 0.00001) and
      overall survival (hazard ratio = 1.86 [95% confidence interval, 1.19-2.91], P =
      0.006). In conclusion, this meta-analysis demonstrates that c-Met overexpression
      is a significant prognostic marker for poor survival in patients who underwent
      surgical resection for PAC.

PMID- 29069853
TI  - Diagnostic ability of intraoperative ultrasound for identifying tumor residual in
      glioma surgery operation.
AB  - Achieving total glioma resection represents a major challenge to neurosurgeons
      with no distinct margin between tumor and surrounding brain tissue. Many imaging
      methods are employed in surgery visualization and resection control. We performed
      this meta-analysis to assess the diagnosis value of intraoperative ultrasound and
      judged whether ultrasound is a suitable tool in detecting glioma residual. The
      databases including PubMed, Embase, Web of Science, China National Knowledge
      Infrastructure (CNKI), Wanfang and Weipu were systematically searched to find out
      relevant studies and published up to May 5, 2017. A total of 14 studies involving
      542 participants met the selection criteria and bivariate mixed effects models
      were used for analysis. The parameters and their corresponding 95% confidence
      interval (CI) were computed on Stata 12.0 software. The pooled sensitivity was
      0.75 (95%CI: 0.62-0.84), specificity was 0.88 (95%CI: 0.79-0.94), positive
      likelihood ratios was 6.27 (95%CI: 3.76-10.47), negative likelihood ratios was
      0.29 (95%CI: 0.20-0.42), diagnostic odds ratios was 21.83 (95%CI: 14.20-33.55)
      and area under the curve of summary receiver operator characteristic was 0.89.
      Stratified meta-analysis showed sensitivity and area under the curve in low-grade
      glioma were both higher than high-grade glioma. The Deek's plot showed no
      significant publication bias (t = -1.03, P = 0.33). Intraoperative ultrasound has
      high overall diagnostic value to identify glioma remnants, especially in low
      grade glioma, which shows a benefit for prognosis and life quality of patients.
      In general, Intraoperative ultrasound is an effective tool for maximizing the
      extent of glioma resection.

PMID- 29069854
TI  - Postoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I
      pulmonary adenocarcinoma.
AB  - BACKGROUND: Patients with pathological stage I pulmonary adenocarcinoma have
      different postoperative prognosis. The aim of this study is to evaluate the
      prognostic significance of preoperative and postoperative serum levels of
      carcinoembryonic antigen (CEA) and CYFRA 21-1 in patients with pathological stage
      I pulmonary adenocarcinoma. MATERIAL AND METHODS: We retrospectively reviewed the
      data of 123 patients who had undergone a complete resection for pathological
      stage I pulmonary adenocarcinoma between 2004 and 2014. The clinical data of each
      patient including age, gender, preoperative and postoperative serum CEA and CYFRA
      21-1 levels, and pathologic stage, was collected for analysis. RESULTS: The CYFRA
      21-1 and CEA level was persistently normal in 80.5% and 77.2% of all patients
      with p-stage I ADC, respectively. The preoperative level was elevated and
      postoperative level declined to normal for CYFRA 21-1 and CEA were in 10.6% and
      13.0% of all patients, respectively. The postoperative CYFRA 21-1 and CEA level
      were high in 8.9% and 9.8% of all patients, respectively. The postoperative 5
      year survival rate of patients with normal, only preoperative high, and
      postoperative high CYFRA 21-1 level was 92.6%, 92.3% and 43.8%, respectively.
      There was a significant difference between postoperative high group and the other
      two groups (p = 0.002). The postoperative 5-year survival rate of patients with
      normal, only preoperative high, and postoperative high CEA level was 90.8%,
      92.3%, and 70.1%, respectively. There was a significant difference between
      postoperative high group and the other two groups (p = 0.019). In univariate
      analysis, degree of differentiation, visceral pleural invasion, tumor size, and
      pTNM stage, was found to be significant independent prognostic factor (p =
      0.014). Multivariate analysis showed that pTNM stage, postoperative CYFRA 21-1
      high level, and postoperative CEA high level was related to the poor prognosis.
      CONCLUSIONS: Patients of p-stage I ADC with postoperative high serum level of
      either CEA or CYFRA 21-1 had poor prognosis. Carefully followed-up might be
      necessary to rule out occult metastasis for these patients, and further clinical
      studies will be necessary to evaluate the efficacy of adjuvant chemotherapy or
      target therapy. Postoperative high serum level of CEA or CYFRA 21-1 might be a
      subtype of p-stage I ADC.

PMID- 29069855
TI  - Rectovaginal fistula after low anterior resection in Chinese patients with
      colorectal cancer.
AB  - Rectovaginal fistula is a postoperative complication of low anterior resection.
      We investigated the incidence of rectovaginal fistula (RVF) after low anterior
      resection, its risk factors and its optimal treatment. We analyzed data from
      1,493 female patients who underwent low anterior resection for colorectal cancer
      between January 2006 and March 2016. We calculated the incidence of RVF and
      performed univariate and multivariate logistic regression analyses to identify
      risk factors. Twenty-four patients experienced RVF, giving an incidence of 1.61%.
      Univariate analysis revealed a short distance between the tumor and the anal
      verge (p < 0.001), longer surgery duration (p = 0.009), unsatisfactory
      anastomosis (p < 0.001), and greater intraoperative blood loss (p = 0.002) to be
      risk factors for RVF. Multivariate analysis showed that only distance between the
      tumor and the anal verge and unsatisfactory anastomosis were risk factors for
      RVF. Sixteen patients (66.7%) healed within a range of 30-1,225 days (median, 210
      days). Twenty-one patients underwent surgery for diverting stoma; of those, 15 of
      them (71.4%) recovering after ostomy. These results indicate the primary risk
      factors for RVF are unsatisfactory anastomosis and short distance between the
      tumor and the anal verge. Most cases of RVF can be healed using a diverting stoma
      alone, without the need for additional surgery.

PMID- 29069856
TI  - Association of lower body mass index with increased glycemic variability in
      patients with newly diagnosed type 2 diabetes: a cross-sectional study in China.
AB  - Previous studies have indicated that the pathogenesis of diabetes differs between
      obese and lean patients. We investigated whether newly diagnosed Chinese diabetic
      patients with different body mass indices (BMIs) have different glycemic
      variability, and we assessed the relationship between BMI and glycemic
      variability. This was a cross-sectional study that included 169 newly diagnosed
      and drug-naive type 2 diabetic patients (mean age, 51.33 +/- 9.83 years; 110
      men). The clinical factors and results of the 75-g oral glucose tolerance test
      were all recorded. Glycemic variability was assessed using continuous glucose
      monitoring. Compared with overweight or obese patients (BMI >= 24 kg/m2),
      underweight or normal-weight patients (BMI < 24 kg/m2) had higher levels of blood
      glucose fluctuation parameters, particularly in terms of mean amplitude of
      glycemic excursion (MAGE 6.64 +/- 2.38 vs. 5.67 +/- 2.05; P = 0.007) and
      postprandial glucose excursions (PPGEs) (PPGE at breakfast, 7.72 +/- 2.79 vs.
      6.79 +/- 2.40, P = 0.028; PPGE at lunch, 5.53 +/- 2.70 vs. 5.07 +/- 2.40, P =
      0.285; PPGE at dinner, 5.96 +/- 2.24 vs. 4.87 +/- 2.50, P = 0.008). BMI was
      negatively correlated with glycemic variability (r = -0.243, P = 0.002). On
      multiple linear regression analyses, BMI (beta = -0.231, P = 0.013) and Insulin
      Secretion Sensitivity Index-2 (beta = -0.204, P = 0.048) were two independent
      predictors of glycemic variability. In conclusion, lower BMI was associated with
      increased glycemic variability, characterized by elevated PPGEs, in newly
      diagnosed Chinese type 2 diabetic patients.

PMID- 29069857
TI  - A phase I study of the SRC kinase inhibitor dasatinib with trastuzumab and
      paclitaxel as first line therapy for patients with HER2-overexpressing advanced
      breast cancer. GEICAM/2010-04 study.
AB  - The anti-HER2 antibody trastuzumab have shown clinical activity in combination
      with chemotherapy in different breast cancer settings. However, most of patients
      treated with this antibody progress after a period of treatment. Activation of
      the kinase SRC has been linked with resistance to trastuzumab in several
      preclinical studies. We designed a phase I clinical study to explore the activity
      of weekly trastuzumab (2 mg/kg) plus paclitaxel (80 mg/m2) in combination with
      the anti-SRC kinase inhibitor Dasatinib in the first line treatment of HER2
      metastatic breast cancer. The primary objective was to determine the maximum
      tolerated dose (MTD) and recommended phase II dose (RP2D); secondary objectives
      included efficacy, objective response rate (ORR), pharmacokinetics and
      pharmacodynamics. A "3+3" design guided dose escalation with two oral dose levels
      of dasatinib: 100mg (DL1) and 140 mg (DL2). 10 patients were included in the
      phase I part. Dasatinib 100 mg q.d. was established as the recommended RP2D. The
      median number of administered cycles was 12 (range, 1 to 18). Grade 3 treatment
      related AEs at DL1 were diarrhea (n = 2), hyponatremia (n = 1), fatigue (n = 1),
      and AST/ALT elevation (n = 1). A significant reduction in p-SRC expression on
      epidermal keratinocytes on sequential skin biopsies was observed. In conclusion,
      we describe the feasibility of the combination of dasatinib, trastuzumab and
      paclitaxel, and its effect on proteins involved in trastuzumab resistance. The
      phase II part of this study is currently evaluating efficacy.

PMID- 29069859
TI  - Primary malignant melanoma of the cervix: Report of 14 cases and review of
      literature.
AB  - PURPOSE: To investigate the clinical characteristics and prognosis of primary
      malignant melanoma of the uterine cervix. RESULTS: The median age of the patients
      was 61.2 years (range, 42-78 years). The median overall survival of the patients
      at stage I, II and III were 39.2 months, 47.8 months and 9.0 months (P=0.574) and
      the 2-year overall survival for each stage were 80.0%, 50.0% and 0.0%
      respectively. Twelve (85.7%) patients developed recurrence and eleven patients
      (78.6%) died. Ten patients received surgery and four patients were treated with
      chemotherapy and/or radiotherapy. Immunotherapy was administrated to two patients
      after surgery. The mean survival time of patients with surgery and without
      surgery were 47.9 vs.7.75 months (P=0.047). Patients received radical
      hysterectomy had longer survival than patients underwent total hysterectomy (66.8
      months vs 19.5 months, P=0.016). METHODS: Clinical data from 14 patients with
      primary malignant melanoma of the cervix between January 1981 and December 2014
      were reviewed. CONCLUSIONS: Patients with primary malignant melanoma of the
      cervix have a poor prognosis. Radical hysterectomy and pelvic lymphnode
      dissection may offer better prognosis for stage I and II patients.

PMID- 29069858
TI  - Hepatocellular carcinoma in hemodialysis patients.
AB  - We investigated the rates and predictors of mortality in hepatocellular carcinoma
      (HCC) patients who were or were not undergoing long-term hemodialysis. The
      participants in this retrospective observational study were 1298 HCC patients
      (60.0 +/- 12.1 years old, 72% male), of whom 172 were undergoing hemodialysis and
      1126 were not. HCC patients on hemodialysis exhibited a higher hepatitis C virus
      carrier rate (49.4% versus 39.3%, P = 0.012), lower hepatitis B virus carrier
      rate (37.2% versus 58.3%, P < 0.001) and lower hepatitis B or C virus carrier
      rate (77.9% versus 89.3%, P < 0.001) than those not on hemodialysis. Serum
      alkaline phosphatase levels were higher in the hemodialysis than non-hemodialysis
      group (162.8 +/- 141.1 u/l versus 124.6 +/- 102.5 u/l, P < 0.001). By the end of
      the analysis, 32.0% of HCC patients on hemodialysis and 28.0% of those not on
      hemodialysis had died. Kaplan-Meier analysis confirmed that cumulative survival
      was poorer in HCC patients on hemodialysis (P = 0.004). In a multivariate Cox
      regression model, hemodialysis (P < 0.001), older age (P < 0.001) and advanced
      tumor stages (P < 0.001) were found to be risk factors for mortality. HCC
      patients on hemodialysis had a 2.036-fold greater chance of death than HCC
      patients not on hemodialysis. Prospective studies with longer follow-ups and
      larger samples are warranted.

PMID- 29069860
TI  - Prognostic analysis of DLBCL patients and the role of upfront ASCT in high
      intermediate and high-risk patients.
AB  - The role of autologous stem cell transplantation (ASCT) as a frontline treatment
      in patients with diffuse large B cell lymphoma (DLBCL) who are in their first
      remission has not been fully elucidated in the rituximab era. We analyzed 272
      DLBCL patients who received 4-6 cycles of R-CHOP (rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone) or R-CHOP followed by ASCT, from January
      2005 to June 2013 in our institution. Multivariate analysis showed the none
      germinal center B cell (non-GCB) subtype (P=0.014, P=0.012) and International
      Prognostic Index (IPI) (3-5) (P=0.004, P=0.016) were independent unfavorable
      predictors of overall survival (OS) and progression-free survival (PFS),
      respectively. To investigate the treatment effect of upfront ASCT, we selected 94
      high-intermediate and high-risk DLBCL patients who achieved complete remission
      after R-CHOP, with 41 in the ASCT and 53 in the non-ASCT groups. Survival
      analysis revealed patients who received upfront ASCT compared with those who did
      not had better OS (3-year OS: 74.5% vs. 50.4%, P=0.029) or PFS (3-year PFS: 59.6%
      vs. 32.1%, P=0.004), suggesting up-front ASCT following R-CHOP could improve the
      outcome of high-intermediate and high-risk DLBCL patients.

PMID- 29069861
TI  - Higher N stage and serum ferritin, but lower serum albumin levels are associated
      with distant metastasis and poor survival in patients with nasopharyngeal
      carcinoma following intensity-modulated radiotherapy.
AB  - PURPOSE: To evaluate the potential risk factors for distant metastasis of
      nasopharyngeal carcinoma in Chinese patients following standard intensity
      modulated radiotherapy and chemotherapy. METHODS: The potential risk factors for
      distant metastasis in 622 patients with newly-diagnosed primary nasopharyngeal
      carcinoma following standard radiotherapy and chemotherapy were evaluated
      retrospectively by stratification, univariate and multivariate analyses. The 5
      year overall survival, distant metastasis-free survival, local recurrence-free
      survival and progression-free survival rates were determined. RESULTS: Univariate
      and multivariate analyses indicated that N2-3 stage, serum ferritin > 300 MUg/L
      and serum albumin < 42 g/L were independent risk factors for distant metastasis
      of nasopharyngeal carcinoma (P < 0.001, P = 0.013, P = 0.002, respectively). A
      risk prediction model was developed as follows: 1) low-risk group: 0-1 risk
      factor; and 2) high-risk group: 2-3 risk factors. Compared with low-risk group,
      the high-risk group had significantly lower 5-year distant metastasis-free
      survival (76.4% vs. 89.6%, P < 0.001), overall survival (76% vs. 85.9%,P <
      0.001), local recurrence-free survival (88% vs. 92.4%, P = 0.029) and progression
      free survival rates (68.2% vs. 83.7%, P < 0.001). In the high-risk group,
      patients with three risk factors had the lowest distant metastasis-free survival
      rate (P = 0.036). CONCLUSIONS: Combination of higher N stage, serum ferritin and
      lower serum albumin levels may be valuable for predicting distant metastasis of
      nasopharyngeal carcinoma patients following standard intensity-modulated
      radiotherapy and chemotherapy.

PMID- 29069862
TI  - The relationship among cardiac structure, dietary salt and aldosterone in
      patients with primary aldosteronism.
AB  - Salt intake is highly associated with cardiac structure in patients with primary
      aldosteronism (PA). We investigated the association among dietary salt intake,
      aldosterone and left ventricular mass in patients with PA. We enrolled 158
      patients with PA and 158 patients with essential hypertension. We measured 24
      hour urinary sodium (UNa) and aldosterone (UAldo) level and echocardiography
      parameters. In patients with PA, the UAldo level was positively correlated with
      left ventricular mass index (LVMI; r=0.231, p=0.007). The UNa level was not
      linearly correlated with left ventricular structural parameters in patients with
      PA. To test if UNa has a non-linear relationship with LVMI among patients with
      PA, we categorized the participants according to the tertile of UNa (low, median,
      and high tertile). PA patients with medium tertile of UNa had significant lower
      LVMI than the other two groups (LVMI: 144.1 +/- 42.9, 121.1 +/- 33.4, and 136.7
      +/- 32.8 g/m2, from the lowest to the highest tertile of Una; analysis of
      variance p=0.006, post-hoc p <0.05). Multifactor analysis of variance confirmed
      this finding after adjustment for clinical parameters. Post-hoc analyses revealed
      that the high UNa tertile was associated with higher left ventricular end
      diastolic volume compared with medium UNa tertile; while the low UNa tertile was
      associated with higher mean wall thickness compared with medium UNa tertile. The
      findings imply the reasons for increased LVMI may be different in patients with
      the highest and lowest UNa tertile. In conclusion, the medium tertile of 24-hour
      UNa is associated with lowest LVMI in patients with PA.

PMID- 29069863
TI  - Combination of platelet count and lymphocyte to monocyte ratio is a prognostic
      factor in patients undergoing surgery for non-small cell lung cancer.
AB  - The aim of this study was to investigate the usefulness of a novel inflammation
      based prognostic system, called COP-LMR (combination of platelet count and
      lymphocyte to monocyte ratio), for predicting postoperative survival of patients
      with non-small cell lung cancer (NSCLC). COP-LMR was calculated on the basis of
      the obtained data. Patients with both an elevated platelet count (PLT) (>30 *
      104mm-3) and a low LMR (<3.6) were assigned a score of 2, and patients with one
      or none of the parameters were assigned a score of 1 or 0, respectively. A total
      of 1120 patients who underwent complete resection were enrolled in this study.
      Multivariate analysis revealed that COP-LMR is an independent prognostic factor
      for disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001).
      Kaplan-Meier analysis and the log-rank test revealed that COP-LMR stratified the
      patients into 3 independent groups (P<0.001). In conclusion, COP-LMR is a
      potential prognostic biomarker in patients undergoing surgery for NSCLC.

PMID- 29069864
TI  - Single-cell genomic analysis of head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) incidence or rates have increased
      dramatically recently with little improvement in patient outcomes. There is an
      unmet need in HNSCC to develop reliable molecular markers capable of evaluating
      patient risks and advising treatments. This review focuses on recent developments
      in single-cell molecular analysis of cancer, and its applications for HNSCC
      diagnosis and treatments. For proof of concept, we examined gene expression
      levels of 62 patients with HNSCC, and correlate the gene expression profiles to
      single-cell gene expression profiles obtained from a pilot single-cell study of
      CCR5-positive breast carcinoma cells. The single-cell molecular analyses
      complemented the lysate data and reveals heterogeneity of oncogenesis pathways
      with the cancer cell population. Our single-cell molecular analysis indicated
      that molecular heterogeneity exists in HNSCC and should be addressed in treatment
      strategy of HNSCC. Single-cell molecular technology can have significant impact
      on diagnosis, therapeutic decision making, and prognosis of HNSCC.

PMID- 29069866
TI  - Germline mutations in pancreatic cancer and potential new therapeutic options.
AB  - Due to short-lived treatment responses in unresectable disease, pancreatic ductal
      adenocarcinoma (PDAC) continues to be one of the deadliest cancers. There is
      availability of new information about germline and sporadic mutations in the
      deoxyribonucleic acid (DNA) damage repair pathway in PDAC in recent decades and
      the expectation is that novel targeted therapies will thus be developed. A
      variety of germline mutations (BRCA2, BRCA1, PALB2, CDKN2A, ATM, TP53 and
      mismatch repair genes MLH1, MSH2, MSH6) have been reported in these patients with
      the highest prevalence being BRCA1/2. Positive results have been reported with
      the use of targeted therapies, particularly poly (ADP-ribose) polymerase
      inhibitors in BRCA-mutated ovarian and breast cancers, and their use is currently
      being investigated in germline-mutated pancreatic cancer. The aim of this review
      is to provide an outline of germline DNA damage repair mutations in pancreatic
      cancer and their effect on the incidence, outcomes and responses to different
      therapeutic options.

PMID- 29069867
TI  - Erlotinib-based doublet targeted therapy versus erlotinib alone in previously
      treated advanced non-small-cell lung cancer: a meta-analysis from 24 randomized
      controlled trials.
AB  - BACKGROUND: To assess the efficacy profile of erlotinib-based doublet targeted
      therapy compared with erlotinib monotherapy for previously treated patients with
      advanced NSCLC, a meta-analysis was performed. PATIENTS AND METHODS: We
      rigorously searched PubMed, Embase, Cochrane and meeting proceedings. Phase
      II/III randomized trials reporting on the efficacy of erlotinib-doublet therapy
      versus single-agent therapy were selected. We estimated the HR for OS, PFS and
      the RR for ORR, DCR, 1-year SR. Phases of trials, targeted signaling pathways,
      EGFR-status and KRAS- status were included in subset analysis. RESULTS: 24
      studies involving 6,196 patients were eligible. In general, the combination
      targeted therapy significantly improved PFS, ORR and DCR. There was also a trend
      showing improved OS and 1-year SR in doublets group, though it was not
      statistically significant. Subgroup analysis suggested PFS improvement in EGFR
      wild-type, KRAS mutant, KRAS wild-type populations. Moreover, patients treated
      with anti-angiogenesis or anti-MET targeted agent revealed a significant benefit
      in PFS. CONCLUSION: In patients with advanced NSCLC, erlotinib-doublets target
      therapy (specially combination with anti-angiogenesis and anti-MET targeted
      agents) was associated with a statistically significantly longer PFS, greater ORR
      and DCR, but the combination did not improve OS and 1-year SR compared with
      erlotinib alone.

PMID- 29069865
TI  - S100A4 in cancer progression and metastasis: A systematic review.
AB  - Metastasis is the leading cause of cancer-related death and directly associates
      with cancer progression, resistance to anticancer therapy, and poor patient
      survival. Current efforts focusing on the underlying molecular mechanisms of
      cancer metastasis attract a special attention to cancer researchers. The
      epithelial-mesenchymal transition is a complex of molecular program during
      embryogenesis, inflammation, tissue fibrosis, and cancer progression and
      metastasis. S100A4, an important member of S100 family proteins, functions to
      increase the tumor progression and metastasis. The molecular mechanisms of S100A4
      involving in the progression and metastasis are diverse in various malignant
      tumors. Detection of S100A4 expression becomes a promising candidate biomarker in
      cancer early diagnosis and prediction of cancer metastasis and therefore, S100A4
      may be a therapeutic target. This review summarized up to date advancement on the
      role of S100A4 in human cancer development, progression, and metastasis and the
      underlying molecular events and then strategies to target S100A4 expression
      experimentally.

PMID- 29069868
TI  - An emerging function of circRNA-miRNAs-mRNA axis in human diseases.
AB  - Circular RNAs (circRNAs), a novel class of long noncoding RNAs, are characterized
      by a covalently closed continuous loop without 5' or 3' polarities structure and
      have been widely found in thousands of lives including plants, animals and human
      beings. Utilizing the high-throughput RNA sequencing (RNA-seq) technology, recent
      findings have indicated thata great deal of circRNAs, which are endogenous,
      stable, widely expressed in mammalian cells, often exhibit cell type-specific,
      tissue-specific or developmental-stage-specific expression. Evidences are arising
      that some circRNAs might regulate microRNA (miRNA) function as microRNA sponges
      and play a significant role in transcriptional control. circRNAs associate with
      related miRNAs and the circRNA-miRNA axes are involved in a serious of disease
      pathways such as apoptosis, vascularization, invasion and metastasis. In this
      review, we generalize and analyse the aspects including synthesis,
      characteristics, classification, and several regulatory functions of circRNAs and
      highlight the association between circRNAs dysregulation by circRNA-miRNA-mRNA
      axis and sorts of diseases including cancer- related and non-cancer diseases."

PMID- 29069869
TI  - Potential applications of MEG3 in cancer diagnosis and prognosis.
AB  - LncRNAs are emerging as integral functional and regulatory components of normal
      biological activities and are now considered as critically involved in the
      development of different diseases including cancer. In this review, we summarized
      recent findings on maternally expressed gene 3 (MEG3), a noncoding lncRNA,
      locates in the imprinted DLK1-MEG3 locus on human chromosome 14q32.3 region. MEG3
      is expressed in normal tissues but is either lost or decreased in many human
      tumors and tumor derived cell lines. Studies have demonstrated that MEG3 is
      associated with cancer initiation, progression, metastasis and chemo-resistance.
      MEG3 may affect the activities of TP53, MDM2, GDF15, RB1 and some other key cell
      cycle regulators. In addition, the level of MEG3 showed good correlation with
      cancer clinicopathological grade. In summary, MEGs is an RNA-based tumor
      suppressor and is involved in the etiology, progression, and chemosensitivity of
      cancers. The alteration of MEG3 levels in various cancers suggested the
      possibility of using MEG3 level for cancer diagnosis and prognosis.

PMID- 29069870
TI  - Tumor-educated mesenchymal stem cells promote pro-metastatic phenotype.
AB  - Multipotent mesenchymal stem cells (MSCs) are recruited into tumor
      microenvironment in response to multiple signals produced by cancer cells.
      Molecules involved in their homing to tumors are the same inflammatory mediators
      produced by injured tissues: chemokines, cytokines and growth factors. When MSCs
      arrive into the tumor microenvironment these are "educated" to have pro
      metastatic behaviour. Firstly, they promote cancer immunosuppression modulating
      both innate and adaptive immune systems. Moreover, tumor associated-MSCs trans
      differentiating into cancer-associated fibroblasts can induce epithelial
      mesenchymal-transition program in tumor cells. This process determinates a more
      aggressive phenotype of cancer cells by increasing their motility and
      invasiveness and favoring their dissemination to distant sites. In addition, MSCs
      are involved in the formation and modelling of pre-metastatic niches creating a
      supportive environment for colonization of circulating tumor cells. The
      development of novel therapeutic approaches targeting the different functions of
      MSCs in promoting tumor progression as well as the mechanisms underlying their
      activities could enhance the efficacy of conventional and immune anti-cancer
      therapies. Furthermore, many studies report the use of MSCs engineered to express
      different genes or as vehicle to specifically deliver novel drugs to tumors
      exploiting their strong tropism. Importantly, this approach can enhance local
      therapeutic efficacy and reduce the risk of systemic side effects.

PMID- 29069872
TI  - Potential therapeutic targets of triple-negative breast cancer based on its
      intrinsic subtype.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subgroup of human breast
      cancer, which is characterized as estrogen receptor (ER) negative, progesterone
      receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2)
      negative. TNBC is the most difficult breast cancer subgroup to treat, due to its
      unresponsiveness to current clinical targeted therapies, high rate of recurrence,
      and poor prognosis. Thus, there is an urgent medical need to identify therapeutic
      targets and develop more effective stratified medicine for the treatment of TNBC.
      Here we review the potential therapeutic targets for TNBC based on its intrinsic
      subtype. We also review the aberrant activated signals found in different
      subgroups of TNBC, including androgen receptor (AR) and PI3K/AKT/mTOR, Notch,
      Wnt/beta-catenin, Hedge-hog, and TGF-beta signaling pathways, which play
      essential roles in multiple development stages of TNBC. The careful analysis of
      these signaling pathways and therapeutic targets would have significant impact on
      the drug development and clinical trials, leading to effective therapies for this
      deadly disease.

PMID- 29069874
TI  - Soft Tissue Reconstruction of Complete Circumferential Defects of the Upper
      Extremity.

PMID- 29069873
TI  - Prognostic value of microRNA expression levels in pancreatic adenocarcinoma: a
      review of the literature.
AB  - BACKGROUND: Clinical and pathologic markers of prognosis and patterns of failure
      help guide clinicians in selecting patients for adjuvant therapy after surgical
      resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the
      prognostic utility of microRNA profiling in numerous malignancies. Here, we
      review and summarize the current literature regarding associations between
      microRNA expression and overall survival in PDAC patients. MATERIALS AND METHODS:
      We conducted a systematic search in the PubMed database to identify all primary
      research studies reporting prognostic associations between tumor and/or serum
      microRNA expression and overall survival in PDAC patients. Eligible articles were
      reviewed by the authors and relevant findings are summarized below. RESULTS: We
      found 53 publications that fit our search criteria. In total, 23 up-regulated and
      49 down-regulated miRNAs have been associated with worse overall survival. MiR-21
      is the most commonly reported miRNA, appearing in 19 publications, all of which
      report aberrant over-expression and association with shorter survival in PDAC.
      Other miRNAs that appear in multiple publications include miR-10b, -21, -34a, 
      155, -196a, -198, -200c, -203, -210, -218, -222, and -328. We summarize the
      preclinical and clinical data implicating these miRNAs in various molecular
      signaling pathways and cellular functions. CONCLUSIONS: There is growing evidence
      that miRNA expression profiles have the potential to provide tumor-specific
      prognostic information to assist clinicians in more appropriately selecting
      patients for adjuvant therapy. These molecules are often aberrantly expressed and
      exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts
      to develop prognostic and predictive molecular signatures, and further elucidate
      miRNA mechanisms of action, are warranted.

PMID- 29069871
TI  - Leptomeningeal disease: current diagnostic and therapeutic strategies.
AB  - Leptomeningeal disease has become increasingly prevalent as novel therapeutic
      interventions extend the survival of cancer patients. Although a majority of
      leptomeningeal spread occurs secondary to breast cancer, lung cancer, and
      melanoma, a wide variety of malignancies have been reported as primary sources.
      Symptoms on presentation are equally diverse, often involving a combination of
      neurological deficits with the possibility of obstructive hydrocephalus.
      Diagnosis is definitively made via cerebrospinal fluid cytology for malignant
      cells, but neuro-imaging with high quality T1-weighted magnetic resonance imaging
      can aid diagnosis and localization. While leptomeningeal disease is still a
      terminal, late-stage complication, a variety of treatment modalities, such as
      intrathecal chemotherapeutics and radiation therapy, have improved median
      survival from 4-6 weeks to 3-6 months. Positive prognosticative factors for
      survival include younger age, high performance scores, and controlled systemic
      disease. In looking to the future, diagnostics that improve early detection and
      chemotherapeutics tailored to the primary malignancy will likely be the most
      significant advances in improving survival.

PMID- 29069875
TI  - Irritated Subtype of Seborrheic Keratosis in the External Auditory Canal.

PMID- 29069876
TI  - Cleft Lip and Palate Repair Using a Surgical Microscope.
AB  - BACKGROUND: Cleft lip and palate repair requires a deep and small surgical field
      and is usually performed by surgeons wearing surgical loupes. Surgeons with
      loupes can obtain a wider surgical view, although headlights are required for the
      deepest procedures. Surgical microscopes offer comfort and a clear and
      magnification-adjustable surgical site that can be shared with the whole team,
      including observers, and easily recorded to further the education of junior
      surgeons. Magnification adjustments are convenient for precise procedures such as
      muscle dissection of the soft palate. METHODS: We performed a comparative
      investigation of 18 cleft operations that utilized either surgical loupes or
      microscopy. Paper-based questionnaires were completed by staff nurses to evaluate
      what went well and what could be improved in each procedure. The operating time,
      complication rate, and scores of the questionnaire responses were statistically
      analyzed. RESULTS: The operating time when microscopy was used was not
      significantly longer than when surgical loupes were utilized. The surgical field
      was clearly shared with surgical assistants, nurses, anesthesiologists, and
      students via microscope-linked monitors. Passing surgical equipment was easier
      when sharing the surgical view, and preoperative microscope preparation did not
      interfere with the duties of the staff nurses. CONCLUSIONS: Surgical microscopy
      was demonstrated to be useful during cleft operations.

PMID- 29069878
TI  - The Effect of Low-Dose Nitroglycerin Ointment on Skin Flap Necrosis in Breast
      Reconstruction after Skin-Sparing or Nipple-Sparing Mastectomy.
AB  - BACKGROUND: Skin flap necrosis is a common complication after mastectomy and
      breast reconstruction. It has been proven that nitroglycerin ointment, as a
      topical vasodilator, can decrease the rate of skin flap necrosis after mastectomy
      and breast reconstruction. However, nitroglycerin can cause several side effects,
      including headache, dizziness, and hypotension. The purpose of this study was to
      evaluate whether the application of a low dose of nitroglycerin ointment reduced
      the rate of skin flap necrosis in breast reconstruction after skin-sparing or
      nipple-sparing mastectomy. METHODS: A total of 73 cases of breast reconstruction
      after nipple-sparing and skin-sparing mastectomy at our institution from March
      2012 to January 2017 were retrospectively studied. Of these patients, 52 received
      nitroglycerin ointment (4.5 mg) application to the skin around the nipple-areolar
      complex from August 2015 to January 2017, while 21 received fusidic acid ointment
      from March 2012 to August 2015. The number of patients who experienced necrosis
      of the breast skin flap was counted in both groups. RESULTS: Skin flap necrosis
      developed in 2 (3.8%) patients who were treated with nitroglycerin ointment and 5
      (23.8%) patients who did not receive nitroglycerin ointment treatment. Patients
      who did not receive nitroglycerin ointment treatment had a significantly higher
      risk of mastectomy skin flap necrosis than patients who did (odds ratio=7.81; 95%
      confidence interval, 1.38 to 44.23; P=0.02). CONCLUSIONS: Low-dose nitroglycerin
      ointment administration significantly decreased the rate of skin flap necrosis in
      patients who underwent breast reconstruction after skin-sparing or nipple-sparing
      mastectomy, without increasing the incidence of the side effects of
      nitroglycerin.

PMID- 29069877
TI  - Is Robot-Assisted Surgery Really Scarless Surgery? Immediate Reconstruction with
      a Jejunal Free Flap for Esophageal Rupture after Robot-Assisted Thyroidectomy.
AB  - Esophageal perforation is a rare but potentially fatal complication of robot
      assisted thyroidectomy (RAT). Herein, we report the long-term outcome of an
      esophageal reconstruction with a jejunal free flap for esophageal rupture after
      RAT. A 33-year-old woman developed subcutaneous emphysema and hoarseness on
      postoperative day1 following RAT. Esophageal rupture was diagnosed by computed
      tomography and endoscopy, and immediate surgical exploration confirmed esophageal
      rupture, as well as recurrent laryngeal nerve injury. We performed a jejunal free
      flap repair of the 8-cm defect in the esophagus. End-to-side microvascular
      anastomoses were created between the right external carotid artery and the
      jejunal branches of the superior mesenteric artery, and end-to-end anastomosis
      was performed between the external jugular vein and the jejunal vein. The right
      recurrent laryngeal nerve injury was repaired with a 4-cm nerve graft from the
      right ansa cervicalis. Esophagography at 1 year after surgery confirmed that
      there were no leaks or structures, endoscopy at 1 year confirmed the resolution
      of vocal cord paralysis, and there were no residual problems with swallowing or
      speech at a 5-year follow-up examination. RAT requires experienced surgeons with
      a thorough knowledge of anatomy, as well as adequate resources to quickly and
      competently address potentially severe complications such as esophageal rupture.

PMID- 29069880
TI  - Instrumentation in Maxillofacial Surgery: Few Practical Tips.
AB  - When a newly inducted plastic surgery resident embarks on maxillofacial surgery,
      with drills, screws, plates and burrs, it seems like a new domain altogether. As
      a new resident, it is truly fascinating as to how such wide variety of bony work
      is done without scarring over the face. Here we discuss a few practical tips
      which the author has learned during his surgical sojourn in residency. It is
      hoped that the readers who are new to maxillofacial surgery, shall find these
      useful.

PMID- 29069879
TI  - The Surgical Impact of E-Cigarettes: A Case Report and Review of the Current
      Literature.
AB  - We report a case of a 51 years old female with a 25 pack year smoking history who
      underwent bilateral mastectomy and immediate tissue expander reconstruction for
      newly diagnosed right breast cancer. The patient reported herself as a non-smoker
      despite significant e-cigarette use, with resulting significant mastectomy skin
      flap necrosis and breast reconstruction failure. Little is known about the
      physiologic effect of e-cigarettes on wound healing and tissue perfusion. To this
      end, we provide an updated review of the impact of e-cigarettes on surgical
      outcomes. PubMed, Ovid MEDLINE, and PRS GO were searched for the terms "e
      cigarette", "electronic cigarette", "e-cig", "electronic nicotine delivery
      system", "vaping", "surgery", "surgical", "peri-operative", "operate",
      "operative", and "wound healing". Abstract review of all articles was performed.
      123 articles returned that contained both variants of e-cigarettes and surgery as
      keywords. Of those, manual assessment returned three articles which were found to
      be relevant to e-cigarette use in the surgical patient. No articles were found
      that compared perioperative complications in e-cigarette versus traditional
      cigarette users in humans. In conclusion, our case report depicts the potential
      dangers associated with e-cigarette use in the surgical patient. There is a
      public misconception that e-cigarettes are healthier than traditional cigarettes
      and as such their use may go unreported by patients. Early evidence suggests e
      cigarettes may induce some of the same physiologic changes as traditional
      cigarettes, and may have a significant deleterious effect on wound healing.

PMID- 29069881
TI  - The Effect of Hyperbaric Oxygen Therapy on a Large Composite Graft in an Ear
      Amputated by a Human Bite.

PMID- 29069882
TI  - Reconstruction of the Foot Using a Superficial Inferior Epigastric Artery Free
      Flap.
AB  - When foot reconstruction is performed in the pretibial area, the ankle, or the
      dorsum of the foot, the need for a reliable flap remains a challenge. We found
      that the superficial inferior epigastric artery (SIEA) free flap can be used as
      an alternative tool for this purpose, as it helps to solve the problems
      associated with other flaps. We describe 2 cases in which we reconstructed the
      foot using an SIEA free flap, which was pliable enough to fit the contours of the
      area. Postoperatively, the flaps were intact and showed excellent aesthetic
      results. Thus, the SIEA free flap can be an alternative tool for patients with a
      low body mass index who undergo reconstructive surgery involving the pretibial
      area, ankle, knee, or dorsum of the foot, all of which require a soft and
      flexible flap.

PMID- 29069883
TI  - Multiple Cutaneous Squamous Cell Carcinomas Arising in Several Body Areas Except
      for the Face.

PMID- 29069884
TI  - Facial Rejuvenation Enhancing Cheek Lift.
AB  - Supported by recent literature on the signs of aging of the middle and lower
      face, our clinical research has documented a loss of volume of the deep
      structural components of the central face and a progressive descent of the
      nasolabial fat and the jowl fat, leading to facial fragmentation. The signs that
      appear around the age of 45 to 50 years are well targeted by the mini-invasive
      technique described here. We focused on refitting the jowl fat and the nasolabial
      fat associated with cutaneous tightening. The use of absorbable barbed sutures
      (Quill) led to significant improvements, enabling the fitting of fat on fat. In
      the past 4 years, 167 operations were performed using this technique. The
      clinical results were very satisfactory, yielding a natural effect caused by the
      mobilization and strong fixation of the nasolabial fat and the jowl fat in the
      direction opposite to their displacement.

PMID- 29069885
TI  - Internal Mammary Artery Perforator Flap for Immediate Volume Replacement
      Following Wide Local Excision of Breast Cancer.
AB  - BACKGROUND: Breast-conserving therapy is defined as a breast-conserving wide
      local excision (WLE) of a mammary tumour combined with postoperative
      radiotherapy. Immediate restoration of the mammary shape by use of breast
      reduction techniques (volume displacement) or tissue replacement techniques
      (volume replacement) is gaining popularity to prevent breast malformation.
      METHODS: To date, using the internal mammary artery perforator (IMAP) flap has
      been suggested for immediate volume replacement after WLE, but has never been
      evaluated in a published study. RESULTS: We applied this flap in 12 women (mean
      age, 56.1 years) after WLE (mean specimen weight, 46.5 g) of the medial aspect of
      the breast. Over a median follow-up of 35.3 months (standard deviation, 1.2
      months), 4 women needed repeated surgery for dog-ear correction of the donor
      site. CONCLUSIONS: In our experience, the use of an IMAP flap was a reliable
      technique with good cosmetic outcomes after oncoplastic reconstruction. In this
      series, donor site revision often proved necessary initially, but we showed that
      this may easily be prevented.

PMID- 29069886
TI  - Liquid-Based Cytology of the Cerebrospinal Fluid in a Case of Cryptococcal
      Meningitis.
AB  - Cryptococcus neoformans is the most common microorganism found in cerebrospinal
      fluid (CSF) cytology and causes life-threatening infections in immunocompromised
      hosts. Although its cytomorphologic features in conventional smear cytology have
      been well described, those in liquid-based cytology have rarely been. A 73-year
      old woman with diffuse large B-cell lymphoma presented with mental confusion and
      a spiking fever. To rule out infectious conditions, CSF examination was
      performed. A cytology slide that was prepared using the ThinPrep method showed
      numerous spherical yeast-form organisms with diameters of 4-11 MUm and thick
      capsules. Occasional asymmetrical, narrow-based budding but no true hyphae or
      pseudohyphae were observed. Gomori methenamine silver staining was positive.
      Cryptococcosis was confirmed in blood and CSF through the cryptococcal antigen
      test and culture. Liquid-based cytology allows for a clean background and
      additional slides for ancillary testing, facilitating the detection of
      microorganisms in CSF specimens, particularly when the number of organisms is
      small.

PMID- 29069887
TI  - Combination of Transient Elastography and an Enhanced Liver Fibrosis Test to
      Assess the Degree of Liver Fibrosis in Patients with Chronic Hepatitis B.
AB  - Background/Aims: Liver stiffness (LS) was assessed using transient elastography,
      and the enhanced liver fibrosis (ELF) test was performed to accurately assess
      fibrotic burden. We validated the LS-ELF algorithm and investigated whether the
      sequential LS-ELF algorithm performs better than concurrent combination of these
      analyses in chronic hepatitis B (CHB) patients. Methods: Between 2009 and 2013,
      222 CHB patients who underwent liver biopsy (LB), as well as LS measurement and
      the ELF test, were enrolled. Results: Advanced fibrosis (>=F3) and cirrhosis (F4)
      were identified in 141 (63.6%) and 118 (53.2%) patients, respectively. Areas
      under receiver operating characteristic curve for LS predictions of >=F3 (0.887
      vs 0.703) and F4 (0.853 vs 0.706) were significantly higher than the ELF test
      (all p<0.001). Based on the LS-ELF algorithm, 60.4% to 71.6% and 55.7% to 66.3%
      of patients could have avoided LB to exclude >=F3 and F4, respectively, whereas
      68.0% to 78.7% and 63.5% to 66.1% of patients could have avoided LB to confirm
      >=F3 and F4, respectively. When confirmation and exclusion strategies were
      applied simultaneously, 69.4% to 72.5% and 60.8% to 65.3% of patients could have
      avoided LB and been diagnosed as >=F3 and F4, respectively. The proportion of
      patients who correctly avoided LB for the prediction of >=F3 (69.4% to 72.5% vs
      42.3% to 59.0%) and F4 (60.8% to 65.3% vs 23.9% to 49.5%) based on the sequential
      LS-ELF algorithm was significantly higher than the concurrent combination (all
      p<0.05). Conclusions: The sequential LS-ELF algorithm conferred a greater
      probability of avoiding LB in CHB patients to diagnose advanced fibrosis and
      cirrhosis, and this test performed significantly better than the concurrent
      combination.

PMID- 29069888
TI  - Tumor Marker Kinetics as Prognosticators in Patients with Unresectable
      Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy.
AB  - Background/Aims: To determine the prognostic value of carcinoembryonic antigen
      (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during
      palliative chemotherapy. Methods: One hundred and twenty-three patients with
      pathologically confirmed unresectable GBC were included. Differences in serum CEA
      and CA 19-9 levels before and after chemotherapy were measured. Receiver
      operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9,
      and combined changes were performed to assess the optimal cutoff values and
      survival rates. Results: Patients with decreased tumor markers had significantly
      better progression-free survival (PFS) and overall survival (OS) than patients
      with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the
      highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In
      the multivariate analysis, increases in serum CA 19-9 during palliative
      chemotherapy in patients with unresectable GBC was an independent prognosticator
      of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020),
      respectively. Patients with increases >10-fold were considered to have
      progressive disease, whereas individuals with increases >3-fold were likely to
      benefit from early imaging follow-up. Conclusions: CA 19-9 kinetics was a
      reliable prognosticator of PFS and OS in patients with unresectable GBC who
      underwent palliative chemotherapy.

PMID- 29069889
TI  - Characterizing Helicobacter pylori cagA in Myanmar.
AB  - Background/Aims: Differences in the Helicobacter pylori infection rate are not
      sufficient to clarify the dissimilarity of gastric cancer incidence between
      Myanmar and its neighboring countries. To better understand this trend, the H.
      pylori virulence gene cagA was characterized in Myanmar. Methods: Glutamate
      proline-isoleucine-tyrosine-alanine (EPIYA) patterns and CagA multimerization
      (CM) motifs of cagA genotypes were examined by performing polymerase chain
      reactions and DNA sequencing. Results: Of 69 tested H. pylori strains, cagA
      positive patients had significantly more severe histological scores in their
      antrum than cagA-negative patients. Sequence analysis revealed that 94.1% of
      strains had Western-type cagA containing an EPIYA motif (92.6%) or EPIYT motif
      (6.4%). The intestinal metaplasia scores in the antral of patients infected with
      the ABC and ABCC types of cagA were significantly higher than those of patients
      with AB-type cagA. Interestingly, in patients infected with H. pylori, 46.3% of
      strains with three EPIYA motifs contained two identical Western-typical CM
      motifs, and these patients showed significantly higher antrum inflammation scores
      than patients infected with two identical nontypical-CM motif strains (p=0.02).
      Conclusions: In Myanmarese strains, Western-type cagA was predominant. The
      presence of CM motifs and the proportion of multiple EPIYA-C segments might
      partially explain the intermediate gastric cancer risk found in Myanmar.

PMID- 29069890
TI  - Long-Term Effects of Helicobacter pylori Eradication on Metachronous Gastric
      Cancer Development.
AB  - Background/Aims: Gastric mucosal atrophy and intestinal metaplasia due to
      Helicobacter pylori infection are the main precursor lesions of gastric cancer.
      The aim of this study was to evaluate the long-term effects of H. pylori
      eradication on the progression of precancerous lesions to metachronous cancer
      after endoscopic resection of early gastric cancer (EGC). Methods: Patients who
      underwent endoscopic resection of EGC were retrospectively reviewed. Changes in
      precancerous lesions and development of metachronous cancer were compared
      according to H. pylori eradication and final infection status. Results: In total,
      565 patients were followed for over 5 years after endoscopic resection of EGC.
      The grade of atrophy on corpus was significantly lower in the H. pylori
      eradicated group than in the persistent group during follow-up (p=0.029). In
      patients <70 years of age, the cumulative incidence rate of metachronous cancer
      was significantly lower in the H. pylori-eradicated group than in the persistent
      group (p=0.018). Age was an independent risk factor for metachronous cancer
      development. Conclusions: H. pylori eradication might prevent the development of
      metachronous cancer in patients <70 years of age by delaying the progression of
      precancerous lesions after endoscopic resection of EGC.

PMID- 29069891
TI  - Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of
      Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease.
AB  - Background/Aims: The aim of this study was to investigate the effects of
      rebamipide on tight junction proteins in the esophageal mucosa in a rat model of
      gastroesophageal reflux disease (GERD). Methods: GERD was created in rats by
      tying the proximal stomach. The rats were divided into a control group, a proton
      pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole
      (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An
      additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R
      group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into
      the esophageal mucosa were measured in isolated esophagi 14 days after the
      procedure. A Western blot analysis was conducted to measure the expression of
      claudin-1, -3, and -4. Results: The mean surface area of mucosal erosions,
      epithelial thickness, and leukocyte infiltration were lower in the PPI group and
      the PPI+R group than in the control group. Western blot analysis revealed that
      the expression of claudin-3 and -4 was significantly higher in the PPI+R group
      than in the control group. Conclusions: Rebamipide may exert an additive effect
      in combination with PPI to modify the tight junction proteins of the esophageal
      mucosa in a rat model of GERD. This treatment might be associated with the relief
      of GERD symptoms.

PMID- 29069892
TI  - Efficacy of a Three-Dimensional-Printed Training Simulator for Endoscopic Biopsy
      in the Stomach.
AB  - Background/Aims: We used three-dimensional (3D) printing technology to create a
      new biopsy simulator for the stomach and investigated its efficacy and realism in
      endoscopic biopsy training. Methods: A novel stomach biopsy simulator, with 10
      biopsy sites, was produced using a 3D printer. We enrolled 26 participants,
      including 10 residents, six first-year fellows, five second-year fellows, and
      five faculty members. We recorded and reviewed five training sessions and
      evaluated the simulator with questionnaires using a 7-point Likert scale.
      Results: The mean completion time (seconds) was 244.8+/-11.5 for the residents,
      107.9+/-33.4 for the first-year fellows, 106.8+/-20.1 for the second-year
      fellows, and 103.8+/-19.2 for the faculty members. The completion time became
      shorter with repetition and was significantly lower for residents by the fifth
      trial (first trial, 347.0+/-159.5; fifth trial, 169.6+/-57.7; p=0.007). The
      faculty members strongly agreed that the simulator realistically reflected
      endoscopic handling and was reasonable for endoscopic training (scores of 6.2+/
      0.8 and 6.4+/-0.9, respectively). Importantly, experienced endoscopists reported
      that the difficulty levels of the 10 biopsy sites in the simulator were a
      realistic match for the actual stomach. Conclusions: This endoscopic biopsy
      simulator created using a 3D printer is a realistic and useful method to improve
      the biopsy skills of trainee endoscopists.

PMID- 29069893
TI  - Enhancement of the Intrinsic Peroxidase-Like Activity of Graphitic Carbon Nitride
      Nanosheets by ssDNAs and Its Application for Detection of Exosomes.
AB  - The present work investigates the capability of single-stranded DNA (ssDNA) in
      enhancing the intrinsic peroxidase-like activity of the g-C3N4 nanosheets (NSs).
      We found that ssDNA adsorbed on g-C3N4 NSs could improve the catalytic activity
      of the nanosheets. The maximum reaction rate of the H2O2-mediated TMB oxidation
      catalyzed by the ssDNA-NSs hybrid was at least 4 times faster than that obtained
      with unmodified NSs. The activity enhancement could be attributed to the strong
      interaction between TMB and ssDNA mediated by electrostatic attraction and
      aromatic stacking and by both the length and base composition of the ssDNA. The
      high catalytic activity of the ssDNA-NSs hybrid permitted sensitive colorimetric
      detection of exosomes if the aptamer against CD63, a surface marker of exosome,
      was employed in hybrid construction. The sensor recognized the differential
      expression of CD63 between the exosomes produced by a breast cancer cell line
      (MCF-7) and a control cell line (MCF-10A). Moreover, a similar trend was detected
      in the circulating exosomes isolated from the sera samples collected from breast
      cancer patients and healthy controls. Our work sheds lights on the possibility of
      using ssDNA to enhance the peroxidase-like activity of nanomaterials and
      demonstrates the high potential of the ssDNA-NSs hybrid in clinical diagnosis
      using liquid biopsy.

PMID- 29069894
TI  - Self-Replicating Catalyzed Hairpin Assembly for Rapid Signal Amplification.
AB  - A rapid signal amplification system based on the self-replicating catalyzed
      hairpin assembly is reported in which two hairpins, H1 and H2, were well-designed
      in which two split target/trigger DNA and two split G-quadruplex sequences were
      respectively integrated into H1 and H2. Target/trigger DNA can be cyclically used
      in this system to form the duplex DNA assemblies (H1-H2), which will bring the
      two G-quadruplex fragments into close-enough proximity to induce the formation of
      intact G-quadruplex as a colorimetric signal readout. Similarly, the two split
      target/trigger DNA sequences will reunite into a DNA sequence that is identical
      to the target/trigger DNA; then, the obtained replica can also be cyclically used
      as a new activator unit to trigger the CHA reaction, leading to the rapidly and
      significantly enhanced formation of target/trigger DNA replicas with the
      concomitant generation of a higher signal. This self-replication-based
      autocatalytic signal amplified approach has been successfully used to develop a
      rapid and visual assay for DNA and small molecule detection.

PMID- 29069895
TI  - Hydrodabcyl: A Superior Hydrophilic Alternative to the Dark Fluorescence Quencher
      Dabcyl.
AB  - Dark fluorescence quenchers are nonfluorescent dyes that can modulate the
      fluorescence signal of an appropriate fluorophore donor in a distance-dependent
      manner. Dark quenchers are extensively used in many biomolecular analytical
      applications, such as studies with fluorogenic protease substrates or nucleic
      acids probes. A very popular dark fluorescence quencher is dabcyl, which is a
      hydrophobic azobenzene derivative. However, its insolubility in water may
      constitute a major drawback, especially during the investigation of biochemical
      systems whose natural solvent is water. We designed and synthesized a new
      azobenzene-based dark quencher with excellent solubility in aqueous media, which
      represents a superior alternative to the much-used dabcyl. The advantage of
      hydrodabcyl over dabcyl is exemplarily demonstrated for the cleavage of the
      fluorogenic substrate hydrodabcyl-Ser-Phe-EDANS by the proteases thermolysin and
      papain.

PMID- 29069896
TI  - Understanding the Lithiation of the Sn Anode for High-Performance Li-Ion
      Batteries with Exploration of Novel Li-Sn Compounds at Ambient and Moderately
      High Pressure.
AB  - Volume expansion and elastic softening of the Sn anode on lithiation result in
      mechanical degradation and pulverization of Sn, affecting the overall performance
      of Li-Sn batteries. It can, however, be overcome with the help of void space
      engineering by using a LixSn phase as the prelithiated anode, where an optimal
      value for x is desired. Currently, Li4.25Sn is known as the most lithiated Li-Sn
      compound, but recent studies have shown that at high pressure, several exotic and
      unusual stoichiometries can be obtained that may even survive decompression from
      high-to-ambient pressure with improved mechanical properties. With a belief that
      hydrostatic pressure may help in realizing Li-richer (x > 4.25) Li-Sn compounds
      as well, we performed extensive calculations using an evolutionary algorithm and
      density functional theory to explore all stable and low-energy metastable Li-Sn
      compositions at pressures ranging from 1 atm to 20 GPa. This not only helped us
      in enriching the chemistry of a Li-Sn system, in general, but also in improving
      our understanding of the reaction mechanism in Li-Sn batteries, in particular,
      and guiding a route to improve the performance of Li-ion batteries through
      synthesis of Li-rich phases. Besides the experimentally known Li-Sn compounds,
      our study reveals the existence of five unreported stoichiometries (Li8Sn3,
      Li3Sn1, Li4Sn1, Li5Sn1, and Li7Sn1) and their associated crystal structures at
      ambient and high pressure. Although Li8Sn3 has been identified as one of the most
      stable Li-Sn compound in the entire pressure range (1 atm-20 GPa) with R3m
      symmetry, the Li-rich compounds like Li3Sn1-P2/m, Li4Sn1-R3m, Li5Sn1-C2/m, and
      Li7Sn1-C2/m are predicted to be metastable at ambient pressure and found to get
      thermodynamically stable at high pressure. Here, the discovery of Li5Sn1 and
      Li7Sn1 opens up the possibility to integrate them as a prelithiated anode for
      efficiently preventing electrochemical pulverization, as compared to the
      experimentally known highest lithiated compound, Li17Sn4.

PMID- 29069897
TI  - Gaining Mechanistic Insight with Control Pulse Slicing: Application to the
      Dissociative Ionization of CH2BrI.
AB  - In quantum control experiments with shaped femtosecond laser pulses, adaptive
      feedback control is often used to identify pulse shapes that can optimally steer
      the quantum system toward the desired outcome. However, gaining mechanistic
      information can pose a challenge due to the varied structural features of the
      control pulses and/or the often complex nature of the associated simulations of
      the experiments. In this article, we introduce control pulse slicing (CPS) as an
      easy-to-implement experimental analysis tool that can be employed directly in the
      laboratory without the need for modeling, to gain mechanistic insights about
      control experiments, regardless of whether the pulse is optimal or chosen by
      other means. As an illustration, we apply CPS to dissociative ionization of
      CH2BrI with mass spectral detection, where two pulses with similar intensities
      are investigated, with each capable of distinctively controlling the ratio of
      Br+/CH2Br+. These two control pulses were, respectively, first identified with
      closed loop and open loop procedures, and then the multispecies experimental data
      was analyzed with CPS. By comparing the dynamical evolution of the observed
      multiple fragment ion yields upon slicing scans of the two distinct pulses, we
      were able to reveal insights about the control mechanism for manipulating the
      objective ratio. In addition, we also identified the relationship between the
      temporal structures of the control pulses and the associated key reaction
      pathways involved in ionic as well as neutral electronic states, in spite of the
      signals only directly being from the ionic species. The CPS technique is not
      limited to controlled fragmentation mass spectrometry, and it may be applied to
      gain mechanistic insights in any control experiment, reflected in the nature of
      the recorded signal.

PMID- 29069898
TI  - [Am]Mn(H2POO)3: A New Family of Hybrid Perovskites Based on the Hypophosphite
      Ligand.
AB  - A family of five hybrid ABX3 perovskites has been synthesized using hypophosphite
      (H2POO)- as the X-site ion. These compounds adopt the general formula
      [Am]Mn(H2POO)3, where Am = guanidinium (GUA), formamidinium (FA), imidazolium,
      triazolium, and dabconium. We explore the diverse structural and phase transition
      behavior of these materials through single-crystal diffraction measurements and
      demonstrate contrasting magnetism in two of the phases, Am = GUA and FA, that
      arises from structural distortions. The results show that hypophosphite
      perovskites offer a promising platform for generating new functional materials.

PMID- 29069899
TI  - Nucleic Acid Self-Assembly Circuitry Aided by Exonuclease III for Discrimination
      of Single Nucleotide Variants.
AB  - Robust and rapid discrimination of one base mutations in nucleic acid sequences
      is important in clinical applications. Here, we report a hybridization-based
      assay exploiting nucleic acid self-assembly circuitry and enzyme exonuclease III
      (Exo III) for the differentiation of single nucleotide variants (SNVs). This one
      step approach combines the merits of discrimination power of competitive DNA
      hybridization probes (probe + sink) with catalytic amplification assisted by Exo
      III. The phosphorothioate bonds modified on a wild-type (WT) specific sink
      inhibit the Exo III digestion; thus, subsequent catalytic amplification magnifies
      only the intended SNV targets. The integrated assay exhibits improved SNV
      discrimination rather than hybridization probes relying solely on competition or
      amplification and enables SNV detection at 1% abundance. Two frequent cancer
      driver mutation sequences (EGFR-L861Q, NRAS-Q61K) were tested. Our strategy
      allows simple sequence design and can easily adapt to multianalyte SNV
      detections.

PMID- 29069900
TI  - A Super-Resolution Probe To Monitor HNO Levels in the Endoplasmic Reticulum of
      Cells.
AB  - Selective detection of nitroxyl (HNO), which has recently been identified as a
      reactive nitrogen species, is a challenging task. We report a BODIPY-based
      luminescence ON reagent for detection of HNO in aqueous solution and in live RAW
      264.7 cells, based on the soft nucleophilicity of the phosphine oxide
      functionality toward HNO. The probe shows high selectivity to HNO over other
      reactive oxygen/nitrogen and sulfur species. Luminescence properties of the
      BODIPY-based chemodosimetric reagent make it an ideal candidate for use as a
      reagent for super-resolution structured illumination microscopy. The viability of
      the reagent for biological in vivo imaging application was also confirmed using
      Artemia as a model.

PMID- 29069901
TI  - Molecular Mechanism of Flavin Photoprotection by Archaeal Dodecin: Photoinduced
      Electron Transfer and Mg2+-Promoted Proton Transfer.
AB  - Photoinduced biochemical reactions are ubiquitously governed by derivatives of
      flavin, which is a key player in a manifold of cellular redox reactions. The
      photoreactivity of flavins is also one of their greatest disadvantages as the
      molecules are sensitive to photodegradation. To prevent this unfavorable
      reaction, UV-light-exposed archaea bacteria, such as Halobacterium salinarum,
      manage the task of protecting flavin derivatives by dodecin, a protein which
      stores flavins and efficiently photoprotects them. In this study, we shed light
      on the photoprotection mechanism, i.e., the excited state quenching mechanism by
      dodecin using computational methodology. Molecular dynamics (MD) simulations
      unraveled the hydrogen bond network in the flavin binding pocket as a starting
      point for proton transfer upon preceding electron transfer. Using high-level ab
      initio quantum chemical methods, different proton transfer channels have been
      investigated and an energetically feasible Mg2+-promoted channel has been
      identified fully explaining previous experimental observations. This is the first
      extensive theoretical study of archaeal dodecin, furthering the understanding of
      its photocycle and manipulation.

PMID- 29069904
TI  - Combination of platelet count and neutrophil-lymphocyte ratio as a prognostic
      marker to predict chemotherapeutic response and survival in metastatic advanced
      gastric cancer.
AB  - AIM: The study evaluated the prognostic impact of combination of platelet count
      and neutrophil-lymphocyte ratio (COP-NLR) for first-line chemotherapeutic
      response and survival outcomes in metastatic advanced gastric cancer patients.
      METHODS: Two hundred and seventy-three patients were categorized into three COP
      NLR groups (COP-NLR 0, 1, 2) according to their platelet count and neutrophil
      lymphocyte ratio. RESULTS: The COP-NLR 0 had a significantly higher disease
      control rate (93%) than the other two groups (p = 0.011). A logistic regression
      model showed that COP-NLR was an independent risk factor for response to
      chemotherapy (odds ratio: 2.247; 95% CI: 1.303-3.874; p = 0.044). The median
      overall survival for COP-NLR 0, 1 and 2 was 14.8, 10.3 and 9.1 months,
      respectively (p = 0.001). CONCLUSION: COP-NLR is a useful predictor of survival
      outcomes and chemotherapeutic response in patients with metastatic advanced
      gastric cancer.

PMID- 29069906
TI  - Parent-observed thematic data on quality of life in children with autism spectrum
      disorder.
AB  - Domains of quality of life in children with autism spectrum disorder have not
      previously been explored and there has been no quality of life measure developed
      for this population. Our study investigated parent observations to identify the
      domains important to children with autism spectrum disorder who also had an
      intellectual disability. In all, 21 parents (19 mothers, 2 fathers) of children
      with autism spectrum disorder (aged 6-17 years) participated in a qualitative
      study to discuss their child's quality of life. Thematic analysis using a
      grounded theory framework was conducted and 10 domains emerged in relation to
      health and well-being, capacity to perform and develop skills in daily life, and
      connections with the community and environment. Unique aspects of quality of life
      included varying levels of social desire, consistency of routines, and time spent
      in nature and the outdoors, which are not comprehensively captured in existing
      measures. Parent observations provide an initial framework for understanding
      quality of life in autism spectrum disorder and support the development of a new
      measure for this population.

PMID- 29069908
TI  - Fluorescence Excitation Spectroscopy for Phytoplankton Species Classification
      Using an All-Pairs Method: Characterization of a System with Unexpectedly Low
      Rank.
AB  - An all-pairs method is used to analyze phytoplankton fluorescence excitation
      spectra. An initial set of nine phytoplankton species is analyzed in pairwise
      fashion to select two optical filter sets, and then the two filter sets are used
      to explore variations among a total of 31 species in a single-cell fluorescence
      imaging photometer. Results are presented in terms of pair analyses; we report
      that 411 of the 465 possible pairings of the larger group of 31 species can be
      distinguished using the initial nine-species-based selection of optical filters.
      A bootstrap analysis based on the larger data set shows that the distribution of
      possible pair separation results based on a randomly selected nine-species
      initial calibration set is strongly peaked in the 410-415 pair separation range,
      consistent with our experimental result. Further, the result for filter selection
      using all 31 species is also 411 pair separations; The set of phytoplankton
      fluorescence excitation spectra is intuitively high in rank due to the number and
      variety of pigments that contribute to the spectrum. However, the results in this
      report are consistent with an effective rank as determined by a variety of
      heuristic and statistical methods in the range of 2-3. These results are reviewed
      in consideration of how consistent the filter selections are from model to model
      for the data presented here. We discuss the common observation that rank is
      generally found to be relatively low even in many seemingly complex
      circumstances, so that it may be productive to assume a low rank from the
      beginning. If a low-rank hypothesis is valid, then relatively few samples are
      needed to explore an experimental space. Under very restricted circumstances for
      uniformly distributed samples, the minimum number for an initial analysis might
      be as low as 8-11 random samples for 1-3 factors.

PMID- 29069911
TI  - Differentiation between papillary renal cell carcinoma and fat-poor
      angiomyolipoma: a preliminary study assessing detection of intratumoral
      hemorrhage with chemical shift MRI and T2*-weighted gradient echo.
AB  - Background Recent literature suggests that intratumoral hemorrhage detection may
      be helpful in differentiating papillary renal cell carcinoma (pRCC) from fat-poor
      angiomyolipoma (fpAML). Purpose To determine whether intratumoral hemorrhage
      detected using chemical shift magnetic resonance imaging (MRI) and T2*-weighted
      (T2*W) gradient echo (GRE) can be used to differentiate pRCC from fpAML. Material
      and Methods This retrospective study included 42 patients with pRCC (n = 28) and
      fpAML (n = 14) who underwent MRI followed by surgery. Two blinded radiologists
      independently assessed the presence of intratumoral hemorrhage using chemical
      shift MRI (decrease in signal intensity from opposed- to in-phase) and T2*W GRE
      ("blooming"). Consensus reading was determined for discrepant cases. MRI findings
      were compared using Chi-square test. Inter-observer agreement was assessed using
      kappa statistics. Results Inter-observer agreement was substantial for both
      sequences ( k = 0.622 and 0.793, P < 0.001). For chemical shift MRI, the
      prevalence of intratumoral hemorrhage was significantly greater in pRCC than in
      fpAML (71.4% versus 28.6%, P = 0.019 for reader 1; 64.3% versus 14.3%, P = 0.003
      for reader 2; and 75% versus 21.4%, P = 0.002 for the consensus). T2*W GRE showed
      a similar tendency (46.4% versus 14.3%, P = 0.049 for both readers; and 50%
      versus 14.3%, P = 0.042 for the consensus). Using the consensus reading,
      sensitivity and specificity of determining pRCC were 75% and 78.6% for chemical
      shift MRI and 50% and 85.7% for T2*W GRE. Conclusion The prevalence of
      intratumoral hemorrhage identified from chemical shift MRI or T2*W GRE was
      significantly different between pRCC and fpAML. These hemorrhage-sensitive MRI
      sequences may be used as an adjunctive tool for discriminating between the two
      entities.

PMID- 29069912
TI  - A Newly Designed Infrared Reflection Absorption Spectroscopy System for In Situ
      Characterization from Ultrahigh Vacuum to Ambient Pressure.
AB  - We present a novel ultrahigh vacuum (UHV) compatible polarization modulation
      infrared reflection absorption spectroscopy (PM-IRRAS) system that is designed
      for in situ surface spectroscopic characterization on a transferable single
      crystalline sample. The innovative design of manipulator rod and high-pressure
      cell (HPC) ensures free movement of the sample between the preparation chamber
      and the HPC, and perfect separation of them during high pressure experiments. The
      pressure in the HPC can be varied from UHV (10-9 mbar) to ambient pressure (1000
      mbar) while keeping the preparation chamber under UHV conditions. The design of
      the transferable sample holder and receiving stage allows precise temperature
      measurement and allows convenient sample changing. In situ IRRAS measurements
      under variable pressure and temperature can be conducted either in the
      conventional mode or with polarization modulation. Other surface characterization
      methods can also use the preparation chamber; thus, the system is endowed with
      the capability for systematic investigations of surface catalytic reactions. A
      case study of CO adsorption and oxidation on Pt(111) demonstrates the performance
      of the system.

PMID- 29069913
TI  - Gender-related association between uric acid, homocysteine, gamma
      glutamyltransferase, inflammatory biomarkers and metabolic syndrome in subjects
      affected by obesity.
AB  - AIM: Evaluation of gender-related differences in uric acid (UA), homocysteine and
      inflammatory biomarkers as metabolic syndrome (MetS) determinants. PATIENTS &
      METHODS: Anthropometric and routine data were obtained from 825 obese subjects
      (591 F, mean age 54 +/- 14 years). RESULTS: Hyperuricemia was 24% in both
      genders. Waist circumference, creatinine, triglycerides, C-reactive protein and
      gamma-glutamyltransferase were identified as UA-independent determinants in
      females and creatinine and insulin in males. Hyperuricemia increased MetS risk in
      both genders (2.8-fold and 1.5-fold in males and females). CONCLUSION: UA and
      gamma-glutamyltransferase positively relate to MetS in both genders, although
      inflammatory abnormalities are closer related to UA and MetS in females. These
      differences in gender physiology may account for epidemiologic gender disparities
      and help to develop gender-targeted clinical strategies.

PMID- 29069914
TI  - Supporting metacognitive monitoring in mathematics learning for young people with
      autism spectrum disorder: A classroom-based study.
AB  - Previous research suggests impaired metacognitive monitoring and mathematics
      under-achievement in autism spectrum disorder. Within educational settings,
      metacognitive monitoring is supported through the provision of feedback (e.g.
      with goal reminders and by explicitly correcting errors). Given the strength of
      the relationship between metacognition, learning and educational attainment, this
      research tested new computer-based metacognitive support (the 'Maths Challenge')
      for mathematics learners with autism spectrum disorder within the context of
      their classroom. The Maths Challenge required learners to engage in metacognitive
      monitoring before and after answering each question (e.g. intentions and
      judgements of accuracy) and negotiate with the system the level of difficulty.
      Forty secondary school children with autism spectrum disorder and 95 typically
      developing learners completed the Maths Challenge in either a Feedback condition,
      with metacognitive monitoring support regarding the accuracy of their answers,
      goal reminders and strategy support, or with No Feedback. Contrary to previous
      findings, learners with autism showed an undiminished ability to detect errors.
      They did, however, demonstrate reduced cohesion between their pre- and post-test
      intentions. Crucially, support from the Feedback condition significantly improved
      task performance for both groups. Findings highlight important implications for
      educational interventions regarding the provision of metacognitive support for
      learners with autism to ameliorate under-performance in mathematics within the
      classroom.

PMID- 29069915
TI  - Aspartic acid derivatized hydroxylated fullerenes as drug delivery vehicles for
      docetaxel: an explorative study.
AB  - The objective of the present study was to deliver docetaxel to cancerous cells
      with enhanced efficacy and safety profile, using aspartic acid linked
      fullerenols. This aspartic acid derivatized fullerenol conjugate linked with
      docetaxel was characterized by UV, FT-IR and NMR spectroscopy. Studies for
      particle size, PDI, zeta potential and FE-SEM were also performed. The conjugate
      was evaluated for release kinetics, cancer cell cytotoxicity, cellular uptake
      using confocal laser microscopy and also for pharmacokinetic profile. Cytotoxic
      studies proved that there was almost 4.3 folds decrease in IC50 with
      significantly enhanced cellular uptake of the nanometric conjugates. It was
      observed that the bioavailability was enhanced by 5.8 folds when compared to that
      of pure DTX. The developed nanoconstructs were erythrocyte compatible and offered
      decreased protein binding. The findings are encouraging and offer a novel carrier
      with enhanced efficacy and safety of a drug, belonging to BCS class IV.

PMID- 29069916
TI  - The Impact of Visibility on Teamwork, Collaborative Communication, and Security
      in Emergency Departments: An Exploratory Study.
AB  - The aim of this study was to examine the influence of visibility on teamwork,
      collaborative communication, and security issues in emergency departments (EDs).
      This research explored whether with high visibility in EDs, teamwork and
      collaborative communication can be improved while the security issues will be
      reduced. Visibility has been regarded as a critical design consideration and can
      be directly and considerably impacted by ED's physical design. Teamwork is one of
      the major related operational outcomes of visibility and involves nurses, support
      staff, and physicians. The collaborative communication in an ED is another
      important factor in the process of care delivery and affects efficiency and
      safety. Furthermore, security is a behavioral factor in ED designs, which
      includes all types of safety including staff safety, patient safety, and the
      safety of visitors and family members. This qualitative study investigated the
      impact of visibility on teamwork, collaborative communication, and security
      issues in the ED. One-on-one interviews and on-site observation sessions were
      conducted in a community hospital. Corresponding data analysis was implemented by
      using computer plan analysis, observation and interview content, and theme
      analyses. The findings of this exploratory study provided a framework to identify
      visibility as an influential factor in ED design. High levels of visibility
      impact productivity and efficiency of teamwork and communication and improve the
      chance of lowering security issues. The findings of this study also contribute to
      the general body of knowledge about the effect of physical design on teamwork,
      collaborative communication, and security.

PMID- 29069918
TI  - "Everything Happens in the Hallways": Exploring User Activity in the Corridors at
      Two Rehabilitation Units.
AB  - OBJECTIVES: This research aimed to examine the role of the corridors in
      specialist inpatient rehabilitation units to inform future design of these
      spaces. BACKGROUND: In healthcare settings, such as rehabilitation units,
      corridors have often been designed simply as spaces allowing movement between
      other locations. However, research suggests that corridors may be places where
      important social and care-related activities take place. How corridors are used
      and understood by patients and staff in inpatient rehabilitation settings is
      unclear, and a greater understanding of the role of corridors in these settings
      could help to inform more supportive design of these spaces. METHODS: Independent
      observations of user activity were conducted at a major metropolitan inpatient
      spinal injury unit (SIU) and brain injury unit (BIU). Interviews were conducted
      with SIU patients ( n = 12), and focus groups were conducted with SIU staff ( n =
      23), BIU patients ( n = 12), and BIU staff ( n = 10). RESULTS: Results from the
      observations showed that the corridors were used frequently across the day,
      particularly by staff. Thematic analysis of staff and patient experiences found
      three key themes describing how corridors were used: (1) moving around, (2)
      delivery and experiences of quality care, and (3) a "spillover space."
      CONCLUSIONS: Results demonstrate that corridors not only have an important role
      as connective spaces but are also used as flexible, multipurpose spaces for
      delivery of quality care and patient experiences. Future design should consider
      how these spaces can more deliberately support and contribute to patient and
      staff experiences of rehabilitation.

PMID- 29069917
TI  - The association between serological features of chronic Chlamydia pneumoniae
      infection and markers of systemic inflammation and nutrition in COPD patients.
AB  - INTRODUCTION: Chlamydia pneumoniae is an obligatory human pathogen involved in
      lower and upper airway infections, including pneumonia, bronchitis. Asymptomatic
      C. pneumoniae carriage is also relatively common. The association of C.
      pneumoniae infections with the chronic obstructive pulmonary disease (COPD)
      course is unclear. OBJECTIVES: The aim of the study was to investigate the
      association between chronic C. pneumoniae infection and clinical features of
      COPD, markers of inflammation and metabolic dysfunction. PATIENTS AND METHODS:
      The study included 59 patients with stable COPD who had no, or had >=2 acute
      exacerbations during last year. The level of IgA and IgG antibody against C.
      pneumoniae, IL-6, IL-8, resistin, insulin, adiponectin and acyl ghrelin was
      measured in serum by enzyme-linked immunosorbent assay (ELISA). RESULTS: No
      differences in clinical and functional data were observed between COPD patients
      without serological features of C. pneumoniae infection and chronic C. pneumoniae
      infection. The level of anti C. pneumoniae IgA significantly correlated with IL
      8, IL-6, resistin concentration in group of frequent exacerbators. IgG level
      correlated negatively with acetyl ghrelin and body mass index (BMI) in patients
      without frequent exacerbations, in contrast to frequent COPD exacerbation group
      where significant correlations between IgG level and BMI was demonstrated. Serum
      IL-6 correlated positively with resistin and insulin and negatively with
      adiponectin in group of patients with serological features of chronic C.
      pneumoniae infection only. CONCLUSIONS: Our study showed that chronic C.
      pneumoniae infection does not influence the clinical course of COPD in the both
      study groups. Chronic C. pneumoniae infections might be associated with a
      distinct COPD phenotype that affects metabolic dysfunction.

PMID- 29069919
TI  - Stereotactic biopsy of cerebellar lesions: straight versus oblique frame
      positioning.
AB  - OBJECTIVE: Biospies of brain lesions with unknown entity are an everyday
      procedure among many neurosurgical departments. Biopsies can be performed frame
      guided or frameless. However, cerebellar lesions are a special entity with a more
      complex approach. All biopsies in this study were performed stereotactically
      frame guided. Therefore, only biopsies of cerebellar lesions were included in
      this study. We compared whether the frame was attached straight versus oblique
      and we focused on diagnostic yield and complication rate. METHODS: We evaluated
      20 patients who underwent the procedure between 2009 and 2017. Median age was
      56.5 years. 12 (60%) Patients showed a left sided lesion, 6 (30%) showed a lesion
      in the right cerebellum and 2 (10%) patients showed a midline lesion. RESULTS:
      The stereotactic frame was mounted oblique in 12 (60%) patients and straight in 8
      (40%) patients. Postoperative CT scan showed small, clinically silent blood
      collection in two (10%) of the patients, one (5%) patient showed haemorrhage,
      which caused a hydrocephalus. He received an external ventricular drain. In both
      patients with small haemorrhage the frame was positioned straight, while in the
      patient who showed a larger haemorrhage the frame was mounted oblique. In all
      patients a final histopathological diagnosis was established. CONCLUSION:
      Cerebellar lesions of unknown entity can be accessed transcerebellar either with
      the stereotactic frame mounted straight or oblique. Also for cerebellar lesions
      the procedure shows a high diagnostic yield with a low rate of severe
      complications, which need further treatment.

PMID- 29069920
TI  - Cleavable PEGylation: a strategy for overcoming the "PEG dilemma" in efficient
      drug delivery.
AB  - To prolong the circulation time of drug, PEGylation has been widely used via the
      enhanced permeability and retention (EPR) effect, thereby providing new hope for
      better treatment. However, PEGylation also brings the "PEG dilemma", which is
      difficult for the cellular absorption of drugs and subsequent endosomal escape.
      As a result, the activity of drugs is inevitably lost after PEG modification. To
      achieve successful drug delivery for effective treatment, the crucial issue
      associated with the use of PEG-lipids, that is, "PEG dilemma" must be addressed.
      In this paper, we introduced the development and application of nanocarriers with
      cleavable PEGylation, and discussed various strategies for overcoming the PEG
      dilemma. Compared to the traditional ones, the vehicle systems with different
      environmental-sensitive PEG-lipids were discussed, which cleavage can be achieved
      in response to the intracellular as well as the tumor microenvironment. This
      smart cleavable PEGylation provides us an efficient strategy to overcome "PEG
      dilemma", thereby may be a good candidate for the cancer treatment in future.

PMID- 29069921
TI  - Adherence of patients with type 2 diabetes mellitus to medications: the role of
      risk preferences.
AB  - OBJECTIVE: To examine whether risk tolerance is associated with adherence to oral
      hypoglycemic agents (OHAs). METHODS: We performed a cross-sectional study among
      adult patients with type 2 diabetes mellitus (n = 308) presenting for routine out
      patient visits, using validated questionnaires to estimate: risk preferences
      (risk-seeking, risk averse, risk neutral), motivation, self-efficacy,
      impulsivity, perception of the disease and of the interpersonal process of care,
      demographic and socioeconomic characteristics; computerized patient medical
      records to estimate disease severity and a computerized database for retrieval of
      medication adherence, 1 year before the interview. Adherence was estimated using
      prescription-based measures of proportion of days covered (PDC). Concurrent
      adherence was calculated as: PDC with >=1 OHAs; average PDC; PDC of >=80% for all
      OHAs. RESULTS: Multivariable ordered logit model revealed that compared to
      others, risk-seeking patients had lower PDC with >=1 OHAs (beta = -0.50, p <=
      .1). Specifically, risk-seeking patients were 11.2 percentage points less likely
      to have >=80% of the follow-up period covered with >=1 OHAs available (p <= .1).
      In addition, risk-seeking patients had lower average PDC (beta = -0.85, p <=
      .05). Specifically, these patients were 19.5 percentage points less likely to
      have an average PDC of >=80% (p <= .05). Multivariable logistic model revealed
      that risk-seeking was associated with lower probability of having PDC >=80% for
      all OHAs in the follow-up period (OR; 90% CI: 0.59; 0.35-0.97). CONCLUSIONS: Risk
      seeking patients are less adherent to OHA medications. Identifying these patients
      may enable practitioners to proactively tailor strategies to improve their
      adherence and health outcomes.

PMID- 29069922
TI  - Resources to cope with stigma related to HIV status, gender identity, and sexual
      orientation in gay men and transgender women.
AB  - The stigma related to HIV status, gender identity, and sexual orientation has
      negative implications for the quality of life of individuals. A qualitative study
      was conducted to explore the resources that these stigmatized groups recognize as
      tools to cope with stigma and maintain their psychological well-being. Four focus
      groups were conducted with gay men and transgender women divided by HIV status. A
      thematic analysis revealed that individual, interpersonal, and institutional
      resources are commonly recognized as coping resources. This article discusses the
      importance of enhancing self-acceptance, social support, and a legal framework
      that legitimizes these groups as right holders.

PMID- 29069923
TI  - Comparison of two assays measuring human chorionic gonadotrophin serum
      concentrations in pregnancy termination and trophoblastic or non-trophoblastic
      tumours.
AB  - BACKGROUND: Differences in human chorionic gonadotrophin (hCG) results provided
      by the commercial immunoassays reflect the heterogeneity of antibodies and the
      use of suboptimal standards. As a consequence, the principal forms of hCG and
      metabolites are differentially detected and the hCG tests are not suited for the
      same clinical applications. Conflicting results are available in the literature
      regarding which hCG variants are recognized by the Roche Elecsys hCG + beta test.
      The aim of our study was to compare the hCG concentrations provided by the
      Siemens Immulite 2000 test and the Roche test as well as to assess the
      concordance between both assays. METHODS: In this purpose, 152 samples obtained
      from women and 44 samples from men were analysed by both tests during the follow
      up of pregnancy termination, gestational trophoblastic disease and malignancies.
      The intermediate precision of the Roche test was also investigated on a pool with
      a low hCG concentration. RESULTS AND CONCLUSIONS: The hCG concentrations measured
      with the Roche test were slightly lower compared with the Siemens assay; mean
      biases of -34.2% and -8% were respectively obtained for hCG values <=100 UI/L and
      higher than 100 UI/L. The overall agreement between both assays was 96.1% for
      women and 97.7% for men. By using an upper reference limit of 3.2 UI/L for women
      and 1.6 UI/L for men, the Roche test demonstrated a respective concordance of
      98.7% and 100%. This test also yielded an excellent precision with a coefficient
      of variation of 2.8% at a mean hCG concentration of 7 UI/L.

PMID- 29069924
TI  - Phytol-loaded PLGA nanoparticle as a modulator of Alzheimer's toxic Abeta peptide
      aggregation and fibrillation associated with impaired neuronal cell function.
AB  - Alzheimer's disease (AD) is an unfavourable neurological condition of the brain
      leading to the loss of behavioural and cognitive skills of the aging population.
      At present, drugs representing cholinesterase inhibitors provide lateral side
      effects to AD patients. Hence, there is a need for improved fabrication of drugs
      without side effects, for which nanoencapsulated bioactive compounds that can
      cross the blood-brain barrier offer new hope as novel alternative treatment
      strategy for AD. This study involved synthesis of phytol loaded poly(lactic-co
      glycolic acid) (PLGA) nanoparticles by solvent evaporation method. Physico
      chemical characterization of phytol-PLGA NPs through the field emission scanning
      electron microscope, dynamic laser scattering (DLS) measurement revealed that the
      particles were nanosize range with smooth surface and spherical morphology.
      Furthermore, the biocompatibility of drug/polymer ratio was investigated by power
      X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopic (FT-IR)
      analysis. The in vitro drug release study showed that the phytol was released in
      a sustained manner. Moreover, phytol-PLGA NPs were able to disrupt amyloid
      aggregates, exhibit anti-cholinesterase and anti-oxidative property and are non
      cytotoxic in Neuro2a cells.

PMID- 29069925
TI  - Two new picrotoxane-type sesquiterpenoid lactones from Dendrobium williamsonii.
AB  - Two new picrotoxane-type sesquiterpenoid lactones, dendrowillins A (1) and B (2),
      together with five known sesquiterpenoids, (-)-picrotin (3), alpha
      dihydropicrotoxinin (4), dendronobilin B (5), amoenin (6), and (-)-10beta,13,14
      trihydroxyalloaromadendrane (7), were isolated from the whole plants of
      Dendrobium williamsonii. Their structures were elucidated by means of extensive
      spectroscopic analysis.

PMID- 29069926
TI  - Prevention of ischemia-reperfusion lung injury during static cold preservation by
      supplementation of standard preservation solution with HEMO2life(r) in pig lung
      transplantation model.
AB  - We describe the results of adding a new biological agent HEMO2life(r) to a
      standard preservation solution for hypothermic static lung preservation aiming to
      improve early functional parameters after lung transplantation. HEMO2life(r) is a
      natural oxygen carrier extracted from Arenicola marina with high oxygen affinity
      developed as an additive to standard organ preservation solutions. Standard
      preservation solution (Perfadex(r)) was compared with Perfadex(r) associated with
      HEMO2life(r) and with sham animals after 24 h of hypothermic preservation
      followed by lung transplantation. During five hours of lung reperfusion,
      functional parameters and biomarkers expression in serum and in bronchoalveolar
      lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO2life(r)
      group led to significant improvement in functional parameters: reduction of graft
      vascular resistance (p < .05) and increase in graft oxygenation ratio (p < .05).
      Several ischemia-reperfusion related biomarkers showed positive trends in the
      HEMO2life(r) group: expression of HMG B1 in serum tended to be lower in
      comparison (2.1 +/- 0.8 vs. 4.6 +/- 1.5) with Perfadex(r) group, TNF-alpha and IL
      8 in BALF were significantly higher in the two experimental groups compared to
      control (p < .05). During cold ischemia, expression of HIF1alpha and histology
      remained unchanged and similar to control. Supplementation of the Perfadex(r)
      solution by an innovative oxygen carrier HEMO2life(r) during hypothermic static
      preservation improves early graft function after prolonged cold ischemia in lung
      transplantation.

PMID- 29069927
TI  - How to perform a cost-effectiveness analysis with surrogate endpoint: renal
      denervation in patients with resistant hypertension (DENERHTN) trial as an
      example.
AB  - Whilst much uncertainty exists as to the efficacy of renal denervation (RDN), the
      positive results of the DENERHTN study in France confirmed the interest of an
      economic evaluation in order to assess efficiency of RDN and inform local
      decision makers about the costs and benefits of this intervention. The
      uncertainty surrounding both the outcomes and the costs can be described using
      health economic methods such as the non-parametric bootstrap. Internationally,
      numerous health economic studies using a cost-effectiveness model to assess the
      impact of RDN in terms of cost and effectiveness compared to antihypertensive
      medical treatment have been conducted. The DENERHTN cost-effectiveness study was
      the first health economic evaluation specifically designed to assess the cost
      effectiveness of RDN using individual data. Using the DENERHTN results as an
      example, we provide here a summary of the principle methods used to perform a
      cost-effectiveness analysis.

PMID- 29069928
TI  - Reductions in emergency department visits after primary healthcare use of the UK
      National Poisons Information Service.
AB  - BACKGROUND: Suspected poisoning is a common cause of hospital admission
      internationally. In the United Kingdom, the National Poisons Information Service
      (NPIS), a network of four poisons units, provides specialist advice to health
      professionals on the management of poisoning by telephone and via its online
      poisoning information and management database, TOXBASE(r). OBJECTIVE: To
      demonstrate the impact of NPIS telephone advice and TOXBASE(r) guidance on
      poisoning-related referrals to emergency departments (ED) from primary healthcare
      settings. METHODS: A telephone survey of primary healthcare providers calling the
      NPIS and an online survey of TOXBASE(r) primary care users were conducted to
      evaluate the effect of these services on poisoning-related ED referrals.
      Enquirers were asked to indicate whether referral was needed before and after
      using these information sources. RESULTS: The number of cases considered by
      enquirers appropriate for ED referral was reduced from 1178 (58.1%) before to 819
      (40.4%) after the provision of telephone advice for 2028 cases (absolute
      reduction 17.7%, 95% CI 14.6, 20.7%) and from 410 (48.2%) before to 341 (40.1%)
      after consideration of TOXBASE(r) guidance for 851 cases (absolute reduction
      8.1%, 95% CI 3.3, 12.9%). By extrapolating these figures over a full year, it is
      estimated that these services prevent approximately 41,000 ED referrals annually.
      CONCLUSIONS: The use of NPIS services significantly reduced ED referrals from
      primary healthcare services with resulting avoided healthcare costs exceeding the
      current annual NPIS budget. Further studies are needed to evaluate other
      potential benefits of accessing NPIS services.

PMID- 29069929
TI  - Recombinant human erythropoietin prevents etoposide- and methotrexate-induced
      toxicity in kidney and liver tissues via the regulation of oxidative damage and
      genotoxicity in Wistar rats.
AB  - Etoposide (ETO) and methotrexate (MTX) are two effective chemotherapeutic drugs.
      However, the clinical use of these drugs is limited by its toxicity in normal
      tissues, especially in kidney and in liver tissues. Recombinant human
      erythropoietin (rhEPO), erythropoietin hormone, has also been shown to exert
      tissue protective effects. The purpose of this study was to explore the
      protective effect of rhEPO against oxidative stress and genotoxicity induced by
      ETO and MTX in vivo. Adult male Wistar rats were divided into 10 groups (6
      animals each): control group, rhEPO alone group, ETO alone group, MTX alone group
      and rhEPO + ETO/MTX groups. In rhEPO + ETO/MTX groups, three doses of
      pretreatment with rhEPO were performed: 1000, 3000 and 6000 IU/kg. Our results
      showed that rhEPO pretreatment protects liver and kidney tissues against
      oxidative stress induced by the anticancer drugs. The glycoprotein decreased
      malondialdehyde (MDA) levels, reduced catalase activity and ameliorated
      glutathione depletion. Furthermore, we showed that rhEPO administration prevented
      drug-induced DNA damage accessed by comet test. Altogether, our results suggested
      a protective role of rhEPO, especially at 3000 IU/kg, against ETO- and MTX
      induced oxidative stress and genotoxicity in vivo.

PMID- 29069930
TI  - Long-term health effects of chemical warfare agents on children following a
      single heavy exposure.
AB  - In the 1980s, villages in the Kurdistan region of Iraq were exposed to chemical
      weapons (CWs), which killed and injured thousands of civilians. There has been no
      clinical assessment of the long-term effects of CWs exposure on those injured. We
      report the first such evaluation of CW effects on long-term health of children.
      Patients from the CW-exposed areas were interviewed to assess previous and
      current clinical history and underwent clinical examination. The status of organs
      known to be targets of CWs, including skin, eyes, respiratory and neuromuscular
      systems, was assessed. Children of similar age and social background, but with no
      history of CW exposure, were selected as a control population. Results showed
      that 70% of children in the CWs group had chronic health problems in contrast to
      3.3% in the unexposed group ( p < 0.0001). Fifty-five per cent of the CW-exposed
      group had long-term visual impairment but none in the unexposed population.
      Thirty-six per cent of the CW-exposed group had chronic dermatological conditions
      compared with 0.8% of the unexposed group ( p < 0.0001), 31% of the CWs group had
      neurological sequelae compared with 0.4% of the unexposed group ( p < 0.0001) and
      51% of the CWs group had long-term respiratory problems compared with 1.5% of the
      unexposed group ( p < 0.0001). Respiratory complaints including asthma, chronic
      bronchitis and bronchiectasis were particularly common. Our study suggests that
      CWs used were probably a combination of sulphur mustard and organophosphate nerve
      agents. Results also indicate that the prevalence of acute and chronic health
      problems following exposure to CW agents appear to be higher in children compared
      with reported data in adults.

PMID- 29069931
TI  - Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery.
AB  - High-density lipoprotein (HDL) and low-density lipoprotein (LDL), as human
      endogenous lipoprotein particles, have low toxicity, high selectivity, and good
      safety. They can avoid the recognition and clearance of human reticuloendothelial
      system. These synthetic lipoproteins (sLPs) have been attracted extensive
      attention as the nanovectors for tumor-targeted drug and gene delivery. Herein,
      recent advances in the field of anticancer based on these two lipid proteins and
      recombinant lipoproteins (rLPs) as target delivery vectors were analyzed and
      discussed.

PMID- 29069932
TI  - Lumbar intravertebral disc herniation secondary to idiopathic calcific discitis.
AB  - Calcific discitis is a well recognized entity in the paediatric population but
      more recently has been increasingly reported in adults. It typically involves the
      lower thoracic vertebrae and is of unknown aetiology. Herniation of the calcified
      fragment is rare but typically occurs out through the annulus fibrosus into the
      canal space. Herein we describe the first reported case of calcific discitis
      involving the lumbar vertebrae with subsequent herniation of the calcified disc
      into and through the anterior aspect of the L5 vertebra. The patient first
      presented with a history of right back pain and leg sciatica. Radiographic
      imaging demonstrated calcification within the L4/5 interspace, which was managed
      with simple analgesia. She subsequently re-presented 24-months later with
      worsening sciatica, right leg weakness and faecal incontinence. No evidence of
      cord or root compression was noted on MRI. However, an abnormality was noted at
      the anterior body of L5 with evidence of superior endplate depression and marrow
      signal change. Subsequent radionucleide bone studies confirmed a solitary focus
      of increased linear activity extending across the width of the L4-L5 interspace.
      Her symptoms were managed medically. Serial radiographic imaging demonstrated
      regression of the disc space calcification and healing of the L5 fracture.
      Despite its sinister presentation this condition was self-limiting. We describe
      the radiographic evolution of this pathology and postulate a putative hypothesis
      through which it may have arisen.

PMID- 29069933
TI  - Envenomation by the noble false widow spider Steatoda nobilis (Thorell, 1875) -
      five new cases of steatodism from Ireland and Great Britain.
AB  - OBJECTIVE: The noble false widow Steatoda nobilis is the only medically
      significant spider known to occur in the British Isles and Ireland, with a single
      case of steatodism ever reported from Great Britain. We present here five new
      cases of envenomations by S. nobilis, three from Ireland and two from Great
      Britain and describe symptoms not previously reported for the genus Steatoda.
      CASE PRESENTATION: Four adult males and one adult female with confirmed S.
      nobilis bites reported their symptoms to the authors. General practitioner chart
      was obtained for case #3. In all five cases, envenomations were immediately
      followed by a sharp and prolonged onset of pain, mild to extensive erythema and
      localised to extensive swelling around the bite site. Additional symptoms include
      moderate to intense pruritus, vasodilation of the capillaries around the bite
      site and a possible minor necrotic wound. CONCLUSION: In all cases, symptoms
      subsided within 48-72 h and no further complications were reported. Envenomations
      by S. nobilis seem to produce symptoms similar (but not identical) to those
      previously reported from other Steatoda sp. Considering their benign outcome,
      envenomations by S. nobilis should still be regarded as of moderate medical
      importance, requiring monitoring and pain management strategies.

PMID- 29069934
TI  - Biological responses to nanomaterials: understanding nano-bio effects on cell
      behaviors.
AB  - The unique properties of nanomaterials in drug delivery and tissue engineering
      have captured a great deal of attention as experimental tools in bioimaging,
      diagnostic, and therapeutic processes. A plenty of research have provided a
      strong evidence that nanostructures not only passively interact with cells but
      also actively engage and mediate cell functions and molecular processes.
      Undoubtedly, it is crucially important to better understand biological responses
      to engineered nanomaterials, especially in view of their potential for biomedical
      applications. In this review, we shall highlight recent advances in exploring
      nano-bio effects in diverse systems of nanoparticles, nanotopographies, and mixed
      composite scaffolds. We will also discuss their manipulating functions on
      cellular behaviors and important biological processes of adhesion, morphology,
      proliferation, migration, differentiation, and even hidden mechanisms including
      molecular signaling pathways. At last, the perspectives will be addressed for
      further directions of nanomaterial designs with the purpose of better drug
      delivery and cell therapies.

PMID- 29069935
TI  - Trastuzumab-modified DM1-loaded nanoparticles for HER2+ breast cancer treatment:
      an in vitro and in vivo study.
AB  - BACKGROUND: Emtansine (DM1) is a highly potent anti-microtubule agent that has
      shown promising results for breast cancer treatment, but side effects limit its
      widespread clinical use. In this research, a new nano-drug was developed to
      integrate DM1 agent with antibody targeting. METHODS: A system of novel
      nanoparticles (NPs) DM1-NPs-trastuzumab (DM1-NPs-Tmab) of DM1 combined with (anti
      HER2 antibody, Herceptin(r), Trastuzumab) was developed for HER2+ breast cancer
      treatment, and its physical characterization and antitumor biological activity
      were investigated. RESULTS: DM1-NPs-Tmab-targeted HER2+ breast cancer cells
      specifically were developed. Compared with naked DM1 and Herceptin, DM1-NPs-Tmab
      showed greater toxicity on HER2+ cancer cells and blocked the HER2-PI3K/Akt cell
      activation pathway. DM1-NPs-Tmab inhibited tumor growth by 88% and had less toxic
      effects in vivo than non-targeting DM1 when administered to MDA-MB-453 xenograft
      bearing mice. CONCLUSION: DM1-NPs-Tmab shows superior anti-tumor efficacy than
      free Herceptin or DM1. DM1-NPs-Tmab is a potential promising formulation for
      targeting biotherapy of HER2+ tumors.

PMID- 29069936
TI  - Correction to: Dong et al., Promising galactose-decorated biodegradable poloxamer
      188-PLGA diblock copolymer nanoparticles of resibufogenin for enhancing liver
      cancer therapy.

PMID- 29069937
TI  - The safety of high-dose insulin euglycaemia therapy in toxin-induced cardiac
      toxicity.
AB  - CONTEXT: High-dose insulin euglycaemia (HIE) is recommended in the management of
      toxin-induced cardiac toxicity, with increasing insulin doses now being used. We
      aimed to investigate the safety of HIE in toxin-induced cardiac toxicity.
      METHODS: This was a retrospective review of cases from two clinical toxicology
      units. Demographics, toxin(s) ingested, clinical effects, investigations (serum
      glucose, electrolytes), treatments (insulin, glucose, electrolyte replacement),
      length of stay (LOS) and outcomes were extracted from the patients' medical
      records. Associations between insulin and glucose/electrolyte homeostasis were
      explored by comparing insulin administration and glucose or electrolyte
      concentrations and replacement. RESULTS: There were 22 patients (12 females),
      median age 57 years (15-88 years) treated with HIE. There were 12 beta-blocker,
      six calcium channel blocker and three combined beta-blocker and calcium channel
      blocker ingestions. A total of 19 patients had a systolic blood pressure <80mmHg
      and 18 patients required inotropes in addition to HIE. There were three deaths.
      Despite glucose and electrolyte replacement, 16 patients (73%) developed
      hypoglycaemia (Reference range [RR] < 3.5 mmol/L or <63 mg/dl). In 7 patients,
      hypoglycaemia was mild (2.5-3.4 mmol/L or 45-62 mg/dl) and in nine was severe
      (<2.5 mmol/L or <45 mg/dl). There were no neurological effects from
      hypoglycaemia. A total of 18 patients (82%) developed hypokalaemia (<3.5 mEq/L).
      In 16 patients, this was mild (2.5-3.4 mEq/L). There were no cardiac arrhythmias
      associated with this hypokalaemia. There was no apparent association between
      insulin dosing and severity of hypoglycaemia or hypokalaemia, or in glucose or
      potassium replacement. Median insulin loading dose was 80U (range 50-125 U) and
      the median maximum insulin infusion rate was 150 U/h (range 38-1500 U/h). Median
      glucose infusions rates were 37.5g/h (range 4-75g/h). There was no apparent
      association between insulin and glucose administration. Glucose was administered
      for a median of 18h after ceasing insulin. The duration of glucose administration
      after ceasing insulin increased with the rate and total insulin administered
      during HIE. DISCUSSION: Despite the benefits of HIE in toxin-induced cardiac
      toxicity, it caused significant disruption to glucose and electrolyte
      homeostasis, although there were no apparent complications from this. There was
      no association by comparing the amount of insulin administered on adverse effects
      or glucose administered, suggesting higher doses of insulin are associated with
      no more adverse effects.

PMID- 29069939
TI  - Two new illudane sesquiterpenoids and one new menthane monoterpene from cultures
      of Craterellus cornucopioides.
AB  - Two new illudane sesquiterpenoids, craterellins D and E (1 and 2), and one new
      menthane monoterpene, 4-hydroxy-4-isopropenyl-cyclohexanemethanol acetate (3),
      were isolated from cultures of Craterellus cornucopioides. Structures of 1-3 were
      elucidated on the basis of extensive spectroscopic analysis. Their cytotoxic
      activities on five tumor cell lines were evaluated.

PMID- 29069940
TI  - Effects of multi-dimensional social capital on mental health of children in
      poverty: An empirical study in Mainland China.
AB  - Using the data of 1314 underprivileged children in Xiushui, China, this study
      adopted an ecological framework to explore how social capital embedded in family,
      peer, school, and community interplay and affect the mental health of poor
      children. Structural equation modeling was employed to verify the hypothesized
      model. The results demonstrated that higher levels of family, peer, and school
      social capital were all associated with better mental health outcomes of children
      in poverty. Moreover, family, peer, and school social capital fully mediated the
      effect of community social capital on children's mental health. Theoretical and
      practical implications were discussed.

PMID- 29069938
TI  - Influence of plate fixation on cervical height and alignment after one- or two
      level anterior cervical discectomy and fusion.
AB  - PURPOSE: To evaluate the efficacy of plate fixation on cervical alignment after
      anterior cervical discectomy and fusion (ACDF) using a stand-alone cage (ACDF
      CA), compared to ACDF performed using a cage and plate fixation (ACDF-CP) and
      ACDF using autologous iliac bone graft and plate fixation (ACDF-AP), for the
      treatment of one- or two-level cervical degenerative disease. A second objective
      was to assess the clinical and radiological outcomes between the groups. METHODS:
      A total of 247 patients underwent ACDF and were divided into three groups: those
      who underwent ACDF-CA (n = 76), ACDF-CP (n = 82) or ACDF-AP (n = 89). Fusion rate
      and time-to-fusion, global cervical and segmental angle, fused segment height,
      subsidence rate, and clinical outcomes, were measured using the visual analogue
      scale (VAS), Oswestry Neck Disability Index (NDI), and Robinson's criteria,
      assessed preoperatively, immediately postoperatively, and at least 24 months,
      postoperatively. RESULTS: ACDF-AP was associated with the shortest mean time-to
      fusion, followed by ACDF-CP and ACDF-CA. Compared to the preoperative status, the
      fused segment height and segmental angle increased in all groups immediately
      postoperatively, being well-maintained in patients who underwent ACDF-AP, while
      decreasing in those who underwent ACDF-CP and ACDF-CA procedures. Global cervical
      lordosis increased with ACDF-AP, but decreased immediately postoperatively with
      ACDF-CP and ACDF-CA, and at the final follow-up. Univariate analysis confirmed
      that a change in fused segment height was positively associated with a change in
      both segmental and global cervical angles. Clinical outcomes, namely VAS and NDI
      scores, as well as Robinson's criteria, were comparable among the three
      techniques. CONCLUSIONS: Supplementation with plate fixation, especially using
      autologous iliac bone graft, is beneficial for maintaining the fused segment
      height and cervical spine curvature, as well as reducing time-to-fusion and
      subsidence rate.

PMID- 29069941
TI  - Posterior cerebral artery giant aneurysm associated with bilateral internal
      carotid artery occlusion in a Klippel-Trenaunay syndrome patient: a case report.
AB  - We experienced an extremely rare case of a giant P1-P2 partially thrombosed
      aneurysm associated with bilateral ICA occlusion in a Klippel-Trenaunay syndrome
      patient. In our experience, direct surgical clipping via a pterional approach is
      generally favored for aneurysms located in the junction of the P1-P2 segments,
      even if they are giant.

PMID- 29069942
TI  - Midostaurin/PKC412 for the treatment of newly diagnosed FLT3 mutation-positive
      acute myeloid leukemia.
AB  - INTRODUCTION: Acute myeloid leukemia (AML) is an aggressive hematologic
      malignancy with inadequate treatment options. Approximately one-third of cases
      have a FLT3-ITD or FLT3-TKD mutation which leads to constitutive tyrosine kinase
      activation which contributes to leukemogenesis. The FLT3-ITD mutation is
      associated with a particularly poor prognosis. Midostaurin is a multi-kinase
      inhibitor active against the FLT3 receptor. Midostaurin was approved by the US
      FDA in April 2017 for treatment of newly diagnosed FLT3-mutant AML in combination
      with chemotherapy. Areas covered: Standard treatment of FLT3-mutant AML and
      outcomes. Early clinical development of midostaurin including pharmacokinetics
      and metabolism. The development of midostaurin in FLT3-mutant AML is then
      outlined including review of the phase I, II, and III trials of midostaurin as a
      single agent and in combination with chemotherapy. Expert commentary: The
      approval of midostaurin represents the first new therapy for AML in several
      decades. It is also the first targeted therapy approved for AML. Future studies
      will focus on defining mechanisms of resistance to midostaurin as well as
      establishing the role of midostaurin in combination with hypomethylating agents
      and as maintenance therapy. Second generation, more potent and selective FLT3
      inhibitors are also in development; these agents need to be compared to
      midostaurin.

PMID- 29069943
TI  - Pregnancy-related osteoporotic vertebral compression fractures in two patients
      treated with low-molecular-weight heparin during pregnancy: case reports.
AB  - Pregnancy-related osteoporosis (PRO) is an uncommon metabolic bone disease that
      can result in vertebral fragility fractures. Here we report two cases of young
      women who had been previously treated with LMWH-enoxaparin and were diagnosed
      with PRO with vertebral fragility fractures after delivery. In first case report,
      a 33-year-old primigravid woman who was treated with 40 mg/day of enoxaparin for
      eight months to prevent venous thromboembolism was presented. After delivery,
      Dual energy X ray absorptiometry (DEXA) revealed osteoporosis in lumbar and
      femoral neck region. In magnetic resonance imaging (MRI), T4-T7 thoracic
      vertebral height losses were detected. In second case report, a 28-year-old
      primigravid woman which was treated with 40 mg/day enoxparin from the second
      month to the birth was presented. Osteoporosis in lumbar region was detected by
      DEXA. MRI revealed T12-L1 and L5 vertebral height losses. In conclusion, PRO can
      cause severe low back pain and should be considered in differential diagnosis. A
      detailed medical history should be essential to detect relationship between LMWH
      and PRO.

PMID- 29069944
TI  - Photosensitive drugs: a review on their photoprotection by liposomes and
      cyclodextrins.
AB  - Nowadays, an exciting challenge in the drug chemistry and technology research is
      represented by the development of methods aimed to protect molecular integrity
      and therapeutic activity of drugs from effects of light. The photostability
      characterization is ruled by ICH (The International Council for Harmonization of
      Technical Requirements for Pharmaceuticals for Human Use), which releases details
      throughout basic protocols of stability tests to be performed on new medicinal
      products for human use. The definition of suitable photoprotective systems is
      fundamental for pharmaceutical manufacturing and for human healthy as well, since
      light exposure may affect either drugs or drug formulations giving rise even to
      allergenic or mutagenic by-products. Here, we summarize and discuss the recent
      studies on the formulation of photosensitive drugs into supramolecular systems,
      capable of entrapping the molecules in a hollow of their structure by weak
      noncovalent interactions and protecting them from light. The best known
      supramolecular matrices belong to the 'auto-assembled' structures, of which
      liposomes are the most representative, and the 'host-guest' systems, of which
      cyclodextrins represent the most common 'host' counterpart. A relevant number of
      papers concerning the use of both liposomes and cyclodextrins as photoprotection
      systems for drugs has been published over the last 20 years, demonstrating that
      this topic captures interest in an increasing number of researchers.

PMID- 29069945
TI  - Higher circulating irisin levels in patients with polycystic ovary syndrome:a
      meta-analysis.
AB  - Insulin resistance (IR) has been reported to be highly associated with the
      pathogenesis of polycystic ovary syndrome (PCOS). Although irisin, a newly
      identified myokine that may be closely associated with IR, has been implicated in
      the development of PCOS, the results are still ambiguous. We performed this meta
      analysis to compare the circulating irisin levels between PCOS and healthy women
      and assess the association of irisin with IR. Published works were retrieved from
      PubMed and Embase databases using combinations of 'irisin' and ('polycystic ovary
      syndrome' or 'PCOS'). Eight studies involving 1918 PCOS patients and 528 controls
      were included in the meta-analysis. Publication bias was observed using a funnel
      plot and Egger's regression asymmetry test. The pooled data indicated that the
      levels of irisin were at least 45.78 ng/ml [95% confidence interval (CI)] (12.45,
      79.12, p = .007) higher in patients with PCOS than that in the healthy controls.
      Additionally, we did not observe a significant correlation between circulating
      irisin levels and IR in study populations, although the results may not be
      reliable for small sample sizes. The current meta-analysis suggested that irisin
      might contribute to the development of PCOS independent of IR.

PMID- 29069946
TI  - Paternal and maternal age as risk factors for schizophrenia: a case-control
      study.
AB  - OBJECTIVE: Advanced parental age might constitute a generic risk factor for
      mental and somatic disorders. The current study tested whether this concerns also
      patients with schizophrenia. METHODS: A total of 231 schizophrenic, 56 other
      severe mental disorders patients and 204 controls were diagnosed according to DSM
      IV-TR. Data were tested with ANOVA models including relative risk and odds
      ratios. RESULTS: Patients with schizophrenia manifested higher paternal (32.55 +/
      6.35 vs. 29.42 +/- 6.07, p < .001) and maternal age (27.66 +/- 5.57 vs. 25.46 +/
      4.52, p < .001). Patients with other mental disorders had higher paternal (33.29
      +/- 8.35; p = .001) but not maternal age (26.69 +/- 5.89; p = .296) compared to
      controls. There was no difference between the two patient groups concerning
      either paternal or maternal age (p > .05). There seems to be a higher risk for
      the development of schizophrenia in offspring with paternal age above 25 years
      and maternal age above 22 years at delivery. CONCLUSIONS: The current study
      provides further support for the suggestion that advanced paternal age
      constitutes a risk factor (in a non-dose dependent and gender-independent way)
      for the development of schizophrenia but also for other mental disorders. In
      contrast, advanced maternal age characterises schizophrenia specifically. The
      higher risk is evident after 25 years of paternal and 22 years of maternal age,
      respectively.

PMID- 29069947
TI  - Development of endometrioma after cervical conization.
AB  - The association between cervical conization and subsequent development of
      endometriosis is uncertain. The objective of this study was to estimate the
      incidence rate of ovarian endometrioma after cervical conization and to determine
      factors associated with the development of endometrioma. One hundred forty-two
      patients who underwent cervical conization at the University of Tokyo Hospital
      between January 2006 and December 2013 were included in the study. Their medical
      records were retrospectively studied until April 2015. The incidence rate of
      postconization endometrioma was calculated. Patients' characteristics (age,
      parity, preoperative and postoperative diagnosis and observation period) were
      analyzed. Six patients developed endometrioma after the cervical conization, and
      the incidence rate of endometrioma among patients who underwent cervical
      conization was 10.8 per 1000 person-year (95%CI 3.6-20.5). Patients' age, percent
      of nulliparous, postoperative diagnosis and observation period were not
      associated with the development of postconization endometrioma. A preoperative
      diagnosis with invasive cancer (p < 0.05) was significantly associated with the
      development of postconization endometrioma. The incidence rate of endometrioma
      among patients who underwent cervical conization in the current study was higher
      than that reported population.

PMID- 29069948
TI  - The economic burden of kidney disorders in Korea.
AB  - AIMS: To estimate the economic burden of kidney disorders in Korea. MATERIALS AND
      METHODS: The economic burden of kidney disorders was estimated using a prevalence
      based approach. Related kidney diseases in patients with kidney disorders (RPWKD)
      were defined using codes from the tenth International Classification of Disease
      (E70-E90, F30-F48, F60-F69, F90-F99, K65-K67, N00-N08, N17-N19, and N30-N39). All
      diseases in patients with kidney disorders (APWKD) were defined as kidney
      disorders that involved all disease codes. Economic costs were divided into
      direct costs (medical costs and non-medical costs) and indirect costs
      (productivity loss because of morbidity and premature mortality). RESULTS: The
      prevalence of kidney disorders increased from 0.08% (2008) to 0.11% (2011). The
      total economic burden of RPWKD also substantially increased from $898.9 million
      (2008) to $1.43 billion (2011). This ~59.4% increase in the economic burden was
      equal to 0.12% of the Korean gross domestic product. The economic burden of APWKD
      also increased during the study period: $1.06 billion (2008), $1.23 billion
      (2009), $1.44 billion (2010), and $1.46 billion (2011). CONCLUSIONS: The present
      study provides the first data regarding the economic burden of kidney disorders
      in Korea. The findings support the need for early intervention services and
      prevention programs to prevent, identify, and manage kidney disorders.

PMID- 29069949
TI  - Fertility sparing surgery in epithelial ovarian cancer in Italy: perceptions,
      practice, and main issues.
AB  - About 2.7% of patients epithelial ovarian cancers (EOC) are younger than 40 and
      present with stage I disease. For this subset of women, the issue of fertility
      sparing surgery (FSS) has become critical. The aim of this survey was to
      investigate the management of EOC patients desiring to preserve fertility in
      Italy. A questionnaire consisting of 30 items was developed to evaluate: patient
      selection criteria, rate of FSS, patient's counseling- and pregnancy-timing,
      fertility preservation, obstetrics, and oncologic outcomes. One expert clinician
      for each of 50 major gynecologic oncology centers was invited to participate.
      Data were entered into a database and statistically analyzed. 74% of
      questionnaires were complete. The proportion of EOC patients treated with FSS was
      <10%, 10%-20% and >20% in 70.3%, 24.3% and 5.4% of cases, respectively. Age,
      fertility preservation desire, histotype, and stage were considered relevant to
      select patients for a conservative treatment for 64.8%, 72.9%, and 78.3% of
      responders, respectively. Only 17 centers (45.9%) resulted to have an assisted
      reproductive technique service and Obstetrics Department. Our survey highlights
      discrepancies among oncologists in the management of patients with early EOC
      undergoing FSS. More efforts should be made to define and broadcast the best
      management before and after surgery.

PMID- 29069950
TI  - The cross-cultural adaptation and psychometric validation of the MSSS-88 for use
      in Italian patients with multiple sclerosis.
AB  - PURPOSE: To cross-culturally translate the Multiple Sclerosis Spasticity Scale
      into Italian and to evaluate its psychometric properties in patients with
      multiple sclerosis. METHODS: The Italian version of Multiple Sclerosis Spasticity
      Scale was developed in accordance with international standards and subsequently
      administered to 232 Italian adults with multiple sclerosis. The following
      psychometric properties were analyzed: internal consistency through Cronbach's
      alpha and item-to-total correlation, dimensionality with factor analysis, and
      convergent and criterion validity through hypotheses-testing, comparing the
      Multiple Sclerosis Spasticity Scale with other outcome measures (Fatigue Severity
      Scale, Multiple Sclerosis Quality of Life, Modified Ashworth Scale, Barthel
      Index, and Expanded Disability Status Scale) and analyzing related constructs.
      Finally, we correlated the MSSS-88 subscales with each other. RESULTS: The final
      Multiple Sclerosis Spasticity Scale version was well-understood by all subjects.
      The internal consistency was good (Cronbach's alpha >=0.90). Factor analysis
      revealed that each subscale was unidimensional. Convergent and criterion validity
      were supported by acceptable correlations with other disease-specific
      questionnaires, according to the a priori expectations. CONCLUSIONS: The final
      Italian Multiple Sclerosis Spasticity Scale version showed robust psychometric
      properties. Therefore, it can be recommended as an assessment tool for clinical
      and research use to evaluate spasticity in Italian patients with multiple
      sclerosis. Implications for rehabilitation The Multiple Sclerosis Spasticity
      Scale was developed to measure patients' perception of the impact of spasticity
      on life of subjects with multiple sclerosis. In a sample of Italian subjects with
      multiple sclerosis, the Multiple Sclerosis Spasticity Scale revealed good
      internal consistency and convergent and criterion validity. Factor analysis
      demonstrated that each subscale was unidimensional. Each subscale can be used to
      assess the impact of spasticity in Italian patients with multiple sclerosis.

PMID- 29069951
TI  - Familial Swyer syndrome: a rare genetic entity.
AB  - Swyer syndrome is a pure gonadal dysgenesis associated with a 46 XY karyotype and
      primary amenorrhea in a phenotypic female. Individuals in this syndrome are at an
      increased risk for development of gonadal malignancies. Swyer syndrome (gonadal
      dysgenesis) running in families is rare event and few such scenarios were
      reported in the literature. Here we are presenting this rare entity involving
      three affected siblings born to a non-consanguineous couple. Index case - A 23
      year-old female with primary amenorrhea is presented with a mass per abdomen. The
      clinical findings and laboratory investigations revealed hypergonadotropic
      hypogonadism picture and, imaging revealed a left ovarian tumor. Primary surgical
      debulking of ovarian cancer was done, histopathology of which revealed a
      dysgerminoma FIGO stage IIIC. The family history of the patient revealed a
      similar pattern as the elder sister had primary amenorrhea and had succumbed to
      ovarian cancer and the younger sister also has primary amenorrhea. Karyotype of
      all the three patients revealed a male genotype with a female phenotype. The
      early diagnosis of the patients with Swyer syndrome is very important because of
      the increased risk for the development of malignancy. This is a rare event to
      have two sisters with ovarian cancers in three siblings affected with familial
      gonadal dysgenesis syndrome each of them having a different genotype and first of
      its kind to ever be reported in literature.

PMID- 29069952
TI  - "I just want my life back!" - Men's narratives about living with fibromyalgia.
AB  - BACKGROUND: Fibromyalgia is characterized by chronic widespread pain and an array
      of other symptoms. It is less common among men than among women and the results
      concerning the severity of men's symptoms are contradictory. The purpose of this
      study was to elucidate the impacts of fibromyalgia on men's daily life and work
      ability. METHODS: The data were collected through life story interviews of five
      men with fibromyalgia. RESULTS: The results of a narrative analysis are presented
      in a form of two model narratives: "Adjusting the life to match the illness" and
      "Being imprisoned by the pain". The first narrative is a description of finding a
      balance between the illness and wellness, whereas the second is an account of
      debilitating symptoms, unsuccessful treatment, and rehabilitation interventions.
      CONCLUSION: The results suggest that adjusting one's activities may help to
      manage the symptoms and to support work ability in many cases but for some
      patients the experience of feeling healthy or pain free might be nothing but a
      fading memory. Narrative approach is well applicable to rehabilitation of
      patients with fibromyalgia: an illness narrative may help the patient and
      professionals to understand the situation better and to set realistic and
      relevant goals for rehabilitation. Implications for rehabilitation In addition to
      chronic pain, men with fibromyalgia suffer from daytime tiredness and cognitive
      challenges that substantially interfere with their work ability and daily
      functioning. Vocational rehabilitation interventions, including e.g., adjustments
      of work tasks and hours, should be started early on to support work ability. The
      results indicate that psychosocial support is needed to improve health related
      quality of life of patients with severe and complex symptoms, especially if
      return-to-work is not an option. Men with fibromyalgia seem to lack peer support
      both in face-to face groups and in on-line groups. "All-male" support groups
      could be explored in rehabilitation settings in the future. Using a narrative
      approach in rehabilitation might result in a shared understanding of the
      patient's situation. This could help the professionals to set more individual,
      realistic, and relevant goals for rehabilitation, which in turn might improve
      rehabilitation outcomes.

PMID- 29069953
TI  - Personalized treatment strategies for elderly patients with myelodysplastic
      syndromes.
AB  - INTRODUCTION: Myelodysplastic syndromes (MDS) are a heterogeneous group of
      hematopoietic disorders characterized by ineffective hematopoiesis and peripheral
      cytopenia, and their possible transformation into acute myeloid leukemia (AML).
      They typically affect the elderly but, when making treatment decisions,
      considering chronological age may be insufficient because it poorly correlates
      with patient frailty: the challenge is to select the optimal treatment in these
      patients by balancing efficacy and toxicity. Areas covered: This review discusses
      the rationale for and methods of personalizing the treatment of elderly MDS
      patients. Expert commentary: Decisions concerning treatment strategies for
      elderly MDS patients should be made after assessing their frailty on the basis of
      a geriatric assessment and an estimate of age-adjusted life expectancy. We
      suggest that all elderly MDS patients should undergo a timed up and go test
      (TUGT) as a preliminary means of identifying frail patients, and that all non
      frail patients should then undergo a comprehensive geriatric assessment (CGA) in
      order to distinguish fit and pre-frail patients. Fit patients should receive
      standard dose treatment; pre-frail patients should receive individualized
      therapy; and frail patients should receive symptom-related therapy. A repeated
      CGA may be useful to evaluate the hematological, cognitive and socio-relational
      effects of MDS treatment.

PMID- 29069954
TI  - The performance of an automatic acoustic-based program classifier compared to
      hearing aid users' manual selection of listening programs.
AB  - OBJECTIVE: To compare preference for and performance of manually selected
      programmes to an automatic sound classifier, the Phonak AutoSense OS. DESIGN: A
      single blind repeated measures study. Participants were fit with Phonak Virto V90
      ITE aids; preferences for different listening programmes were compared across
      four different sound scenarios (speech in: quiet, noise, loud noise and a car).
      Following a 4-week trial preferences were reassessed and the users preferred
      programme was compared to the automatic classifier for sound quality and hearing
      in noise (HINT test) using a 12 loudspeaker array. STUDY SAMPLE: Twenty-five
      participants with symmetrical moderate-severe sensorineural hearing loss.
      RESULTS: Participant preferences of manual programme for scenarios varied
      considerably between and within sessions. A HINT Speech Reception Threshold (SRT)
      advantage was observed for the automatic classifier over participant's manual
      selection for speech in quiet, loud noise and car noise. Sound quality ratings
      were similar for both manual and automatic selections. CONCLUSIONS: The use of a
      sound classifier is a viable alternative to manual programme selection.

PMID- 29069955
TI  - Shatavarin IV elicits lifespan extension and alleviates Parkinsonism in
      Caenorhabditis elegans.
AB  - Shatavarin IV (SIV), a steroidal saponin, is a major bioactive phytomolecule
      present in roots of Asparagus racemosus (Liliaceae) known for its anticancer
      activity. Age-associated neurodegenerative Parkinson's disease (PD) is
      characterised by alpha-synuclein aggregation in dopaminergic neuron resulting in
      neurodegeneration. The invention of bioactive molecules that delay aging and age
      associated disorders endorses development of natural phytomolecule as a
      therapeutic agent for curing age-related diseases. Therefore, the present study
      for the first time explores the potential of SIV against aging and Parkinsonism
      utilising Caenorhabditis elegans model system. SIV significantly attenuated
      oxidative stress in terms of intracellular reactive oxygen species (ROS) as well
      as oxidative damage including protein carbonylation and also promotes longevity.
      SIV also significantly increased the mRNA expression of stress responsive genes
      namely sod-1, sod-2, sod-3, gst-4, gst-7 and ctl-2 suggesting its anti-oxidant
      property that might be contributed in the modulation of oxidative stress and
      promoting lifespan. Additionally, SIV improved PD symptoms by reducing the alpha
      synuclein aggregation, lipid accumulation and enhancing dopamine level.
      Altogether, present findings indicate that SIV possibly utilising ubiquitin
      mediated proteasomal system and attenuating oxidative stress by up-regulating PD
      associated genes pdr-1, ubc-12 and pink-1. Therefore, this study is a forward
      step in exploring the anti-aging and anti-Parkinsonism potential of bioactive
      compound SIV in C. elegans.

PMID- 29069956
TI  - Falls among full-time wheelchair users with spinal cord injury and multiple
      sclerosis: a comparison of characteristics of fallers and circumstances of falls.
AB  - PURPOSE: The purpose of this study is to (1) explore and (2) compare
      circumstances of falls among full-time wheelchair users with spinal cord injury
      (SCI) and multiple sclerosis (MS). METHODS: A mixed method approach was used to
      explore and compare the circumstances of falls of 41 full-time wheelchair users
      with SCI (n = 23) and MS (n = 18). In addition to collecting participants'
      demographic information (age, gender, type of wheelchair used, duration of
      wheelchair use, and duration of disability), self-reported fall frequency in the
      past 6 months, self-reported restriction in activity due to fear of falling and
      the Spinal Cord Injury-Fall Concerns Scale (SCI-FCS) was collected. Qualitative
      data in the form of participants' responses to an open-ended question yielding
      information regarding the circumstances of the most recent fall were also
      collected. To examine differences in survey outcomes and demographic
      characteristics between participants with SCI and MS, independent t-tests and
      Pearson's Chi-square tests were used. Qualitative data were analyzed with a
      thematic analysis. RESULTS: Statistical analysis revealed that individuals with
      MS (mean =3.3) had significantly higher average SCI-FCS than individuals with SCI
      (mean =2.4). The analysis of the participants' descriptions of the circumstances
      of their most recent falls resulted in three main categories: action-related fall
      contributors (e.g., transfer), (2) location of falls (e.g., bathroom), and (3)
      fall attributions (e.g., surface condition). CONCLUSIONS: The results from this
      study helped to understand fall circumstances among full-time wheelchair users
      with MS and SCI. Findings from this study can inform the development of evidenced
      based interventions to improve the effectiveness of clinically based treatment
      protocols. Implications for rehabilitation Falls are a common health concern in
      full-time wheelchair users living with multiple sclerosis and spinal cord injury.
      The circumstances surrounding falls reported by full-time wheelchair users living
      with multiple sclerosis and spinal cord injuries were found to be multifactorial.
      The complex nature of falls must be taken into consideration in the development
      of fall prevention programs. Findings from this study can inform the development
      of comprehensive evidence-based, population-specific interventions to manage
      falls among full-time wheelchair users living with multiple sclerosis and spinal
      cord injury.

PMID- 29069957
TI  - Investigating the relationship between 25-hydroxyvitamin D and thyroid function
      in second-trimester pregnant women.
AB  - This study aims to explore the correlation between serum 25-hydroxyvitamin D and
      thyroid hormones during the second trimester. In total, 277 pregnant women at 13
      28 weeks of gestation were enrolled. According to the level of thyrotropic
      stimulating hormone, they were divided into a reduced TSH group, a normal TSH
      group and an elevated TSH group. In this study, we found that the prevalence of
      vitamin D deficiency was as high as 94.58%. The 25-hydroxyvitamin D level in the
      reduced TSH group was lower than that in the normal thyroid function group (p =
      .0005), and the 25-hydroxyvitamin D level in the elevated TSH group was higher
      than that in normal TSH group (p=.0339). A positive correlation was observed
      between 25-hydroxyvitamin D and thyrotropic-stimulating hormone (r = 0.3034, p =
      .0000). Furthermore, 25-hydroxyvitamin D was negatively correlated with the free
      thyroxine level (r = -0.1286, p = .0323) as well as the free triiodothyronine
      level (r = 0.1247, p = .0380). These data suggest that the relationships between
      25-hydroxyvitamin D and thyroid parameters were characterized during the second
      trimester. Pregnant women in the second-trimester who are diagnosed with
      transient hyperthyroidism should be evaluated for the possibility of vitamin D
      deficiency.

PMID- 29069958
TI  - PD-L1 immunohistochemistry for non-small cell lung carcinoma: which strategy
      should be adopted?
AB  - INTRODUCTION: PD-L1 detection with immunohistochemistry (IHC) is the only
      predictive biomarker available to date for PD-L1/PD1 immunotherapy in thoracic
      oncology. While many studies have been published on this biomarker, they raise a
      number of questions concerning mainly, (i) the type of antibody for use and its
      condition of utilization, (ii) the threshold to be used, (iii) the message and
      information to communicate to the thoracic oncologist and, (iv) the adoption of
      this methodology as part of the daily practices of a pathology laboratory. Areas
      covered: This review provides an update on the use of the different PD-L1
      antibodies for IHC in the context of metastatic non-small cell lung cancer
      (NSCLC) and discusses their use as companion or complementary diagnostic tests.
      The limits of PD-L1 IHC as a predictive test, the precautions to be adopted as
      well as some perspectives will then be considered. Expert commentary: IHC for PD
      L1 can be considered as a theranostic test, which implies providing an extremely
      reliable result that avoids any false positive and negative results. PD-L1 IHC
      requires considerable expertise and specific training of pathologists. PD-L1 IHC
      can be a companion or complementary diagnostic test depending on the clone
      employed, the molecular therapy prescribed and the indication of use.

PMID- 29069959
TI  - The liquid biopsy: a tool for a combined diagnostic and theranostic approach for
      care of a patient with late-stage lung carcinoma presenting with bilateral ocular
      metastases.
AB  - INTRODUCTION: Liquid biopsies (LB) are used routinely in clinical practice in two
      situations for late stage non-small-cell lung cancer (NSCLC) patients, (i) at the
      initial diagnosis when looking for activating mutations in EGFR in the absence of
      analyzable tissue DNA and, (ii) during tumor progression on a tyrosine kinase
      inhibitor treatment to look for the resistance mutation T790M in EGFR. LB is not
      presently recommended in daily practice for the diagnosis of NSCLC. Areas
      covered: We report the diagnosis of a NSCLC in a patient with bilateral ocular
      metastases after detection of a deletion in exon 19 of EGFR when using plasma
      DNA. Without histological analysis, the origin of the primary ocular metastasis
      was uncertain. In this context, a LB showing an activating mutation in EGFR and
      circulating tumor cells positive for TTF1 led to the diagnosis of NSCLC and
      targeted therapy. Expert commentary: When no tumor tissue sample is available a
      LB can be used to diagnose for metastatic NSCLC, when a mutation in EGFR is
      identified. While a tissue biopsy is the gold standard approach for the diagnosis
      of a NSCLC and for identification of activating mutations, LB can exceptionally
      provide both a diagnosis of the primitive tumor and indicate appropriate therapy
      based on a molecular analysis.

PMID- 29069960
TI  - 4-(4-Hydroxy-3-methoxyphenyl)-2-butanone modulates redox signal in gamma
      irradiation-induced nephrotoxicity in rats.
AB  - Cellular exposure to ionising radiation leads to oxidative stress events, which
      refer to elevated intracellular levels of reactive oxygen species (ROS). The
      elevated levels of ROS significantly contributed to gamma-radiation (IR) induced
      cytotoxicity. In an attempt to minimise these cytotoxic effects, antioxidant
      compounds have been identified to counteract radiation- associated toxicities. We
      mainly aimed to study the protective effect of 4-(4-hydroxy-3-methoxyphenyl)-2
      butanone (HMB) on IR-induced nephrotoxicity, whereas it was previously shown to
      have anti-inflammatory effects in different inflammation models. Animals were
      treated orally with HMB (25 mg/kg b.wt daily) then performed by whole-body gamma
      irradiation of animals with 6 Gy; a single dose applied on the 15th day and
      animals were sacrificed at the end of the 23rd day. It was found that IR exposure
      significantly induced renal oxidative injury that accompanied by inflammatory
      disturbance. Also, NADPH oxidase and iNOS gene expressions were significantly up
      regulated, while the mitochondrial enzymes (complex I & II) were significantly
      down-regulated in IR exposed animals. Additionally, Western immunoblotting
      analysis of signalling growth factor protein; p38 MAPK was significantly
      overexpressed. Interestingly, HMB treatment showed statistically significant
      amelioration in parameters with an improved histological structure upon the IR
      induced nephrotoxicity. It can be concluded that modulation of NADPH-oxidase,
      iNOS and mitochondrial enzymes by HMB might be responsible for the amendment of
      the antioxidant status and impairment of p38 MAPK signal, thus attenuate the
      nephrotoxicity induced post IR exposure.

PMID- 29069961
TI  - Factors affecting hearing deterioration in vestibular schwannoma patients treated
      with gamma knife radiosurgery: the Asan Medical Center experience.
AB  - OBJECTIVES: To investigate the changes in hearing and to determine factors
      predicting hearing deterioration in patients with vestibular schwannoma (VS) who
      undergo gamma knife radiosurgery (GKRS). DESIGN: A retrospective review of
      medical records in patients diagnosed with VS and initially treated with GKRS at
      a tertiary care medical center between 1995 and 2015 was performed. Tumor factors
      (location, volume), parameters related to irradiation to the tumor and cochlea,
      and distance between the tumor and cochlea were reviewed. RESULTS: Fifty-six
      patients were included in the final analysis with a mean observation period
      following GKRS as 24.4 +/- 27.8 months. Prior to GKRS, the average pure tone
      threshold at 500, 1k, 2k, and 4k Hz (PTA4) was 51.0 +/- 29.7 dB HL. After GKRS,
      the mean PTA4 was 71.6 +/- 33.3 dB HL. Significant independent odds ratios for
      hearing deterioration were 8.5 for extracanalicular tumors, 18.8 for more than 10
      shots in GKRS, and 12.2 for a distance between the tumor center and cochlea
      modiolus less than 20 mm. CONCLUSIONS: A significant hearing deterioration was
      shown in 2 years after GKRS. Tumor location, number of radiation shots, and
      distance between the tumor and cochlea affected hearing level after GKRS.

PMID- 29069962
TI  - Limitations of quantiferon-TB gold assay for screening of psoriasis patients
      prior to anti-tumour necrotic factor treatment.

PMID- 29069963
TI  - Radiological analysis of minimal safe distance and optimal screw angle to avoid
      facet violation in open-door laminoplasty using precontoured plate.
AB  - PURPOSE: This study aimed to present radiologic analysis of minimal safe distance
      (MSD) and optimal screw angle (OSA) that enables to fix screws in a lateral mass
      safely without facet joint violation in open-door laminoplasty using a plate.
      METHODS: A retrospective analysis was made of 22 patients (male: 17; female: 5),
      average age 62 years. Seventy-nine lateral mass screws were fixed among a total
      of 158 screws. MSD that doesn't allow 5-mm screws to violate a facet joint was
      measured for C3-C7 and a comparative analysis was performed. If the MSD is not
      secured, the OSA to be given to the cephalad direction is calculated to avoid
      violation of the facet joint. RESULTS: The screws violating inferior facet joints
      accounted for 34.1% of the screws fixed in inferior lateral mass. Joint surface
      to distal mini-screw distances were 3.18 +/- 1.46 mm and 4.75 +/- 1.71 mm in
      groups of facet joint violation and non-facet violation (FV), respectively ( p =
      0.001). When 5-mm screws were inserted into a lateral mass, MSD was 4.39 +/- 0.83
      mm. The average MSD of C3, C4, and C5 was 4.05 +/- 0.78 mm, 4.10 +/- 0.70 mm, and
      4.26 +/- 0.74 mm, respectively. There was no significant differences among levels
      ( p > 0.05). The average MSD of C6 and C7 was 4.92 +/- 0.81 mm and 4.80 +/- 0.96
      mm, respectively, showing significant differences from those of C3, C4, and C5 (
      p < 0.05). If 6 mm of the MSD isn't secured, OSA showed in the cephalad direction
      of 11.5 degrees  for 5 mm and 22 degrees  for 4 mm approximately. CONCLUSION: We
      suggest that mini-screw on lateral mass can be fixed safely without FV, if they
      are fixed at MSD of 6 mm from a joint surface. Facet joint violation doesn't
      occur if an OSA is given in the cephalad direction in case of not enough MSD for
      mini-screws.

PMID- 29069965
TI  - Twelve tips for developing an OSCE that measures what you want.
AB  - The Objective Structured Clinical Examination (OSCE) is used globally for both
      high and low stakes assessment. Despite its extensive use, very few published
      articles provide a set of best practices for developing an OSCE, and of those
      that do, none apply a modern understanding of validity. This article provides 12
      tips for developing an OSCE guided by Kane's validity framework to ensure the
      OSCE is assessing what it purports to measure. The 12 tips are presented in the
      order they would be operationalized during OSCE development.

PMID- 29069964
TI  - A point on points: Awarding publication points for foundation posts is poor
      practice.

PMID- 29069966
TI  - Seasonal occurrence, removal and risk assessment of 10 pharmaceuticals in 2
      sewage treatment plants of Guangdong, China.
AB  - A long-term investigation, which covered 10 sampling campaigns over 3 years, was
      performed to evaluate the occurrence, removal and risk of 10 pharmaceuticals in 2
      full-scale sewage treatment plants (STPs) in Guangdong, South China. Target
      pharmaceuticals except for clofibrate and ibuprofen were detected in every
      sample, with mean concentrations of 12.5-685.6 and 7.9-130.3 ng/L in the influent
      and effluent, respectively. Salicylic acid was the most abundant compound in both
      the influents and effluents in the two STPs. For most pharmaceuticals, the
      seasonal variation in the influent showed the highest concentrations in January
      and lowest concentrations in July due to their consumption and rainfall.
      Ibuprofen and fenoprofen presented high removal rates (>90%) and some of the
      targets such as gemfibrozil, mefenamic acid, tolfenamic acid and diclofenac were
      detectable with significantly higher mass loads in effluents than in influents.
      Studies of the five efficiently eliminated pharmaceuticals show that the primary
      treatment and secondary treatment contributed to most pharmaceutical removal, the
      anoxic tank made a negligible contribution to their elimination. According to the
      results produced from the calculation of the risk quotient, only diclofenac might
      pose a risk to the aquatic environment.

PMID- 29069968
TI  - Corrigendum.
AB  - Eglseder, K., & Demchick, B. (2017). Sexuality and Spinal Cord Injury: The Lived
      Experiences of Intimate Partners. Occupation, Participation and Health, 37, 5-16.
      doi: 10.1177/1539449217701394 This article that appeared in Issue 37:3 of
      Occupation, Participation and Health has the following corrected information: On
      p. 126, in the first sentence of the last paragraph under Procedures, the text
      "The current study was approved by the BLIND University" should instead read,
      "The current study was approved by the Towson University" On p. 126, in the
      second paragraph on the right column, the text "The researcher then discussed
      their responses to both administrations of the Checklist and probed to into
      identified needs to gain a better understanding of the participants' responses"
      should instead read "The researcher then discussed their responses to both
      administrations of the Checklist and probed into identified needs to gain a
      better understanding of the participants' responses" On p. 129, in the third
      paragraph on the left column under Theme 2, the text "On participant described
      her feelings relating to her spouse's need to take medication to get an erection
      and his lack of ability to fully participate," should instead read "One
      participant described her feelings relating to her spouse's need to take
      medication to get an erection and his lack of ability to fully participate,".

PMID- 29069967
TI  - Bayesian imputation of time-varying covariates in linear mixed models.
AB  - Studies involving large observational datasets commonly face the challenge of
      dealing with multiple missing values. The most popular approach to overcome this
      challenge, multiple imputation using chained equations, however, has been shown
      to be sub-optimal in complex settings, specifically in settings with longitudinal
      outcomes, which cannot be easily and adequately included in the imputation
      models. Bayesian methods avoid this difficulty by specification of a joint
      distribution and thus offer an alternative. A popular choice for that joint
      distribution is the multivariate normal distribution. In more complicated
      settings, as in our two motivating examples that involve time-varying covariates,
      additional issues require consideration: the endo- or exogeneity of the covariate
      and its functional relation with the outcome. In such situations, the implied
      assumptions of standard methods may be violated, resulting in bias. In this work,
      we extend and study a more flexible, Bayesian alternative to the multivariate
      normal approach, to better handle complex incomplete longitudinal data. We
      discuss and compare assumptions of the two Bayesian approaches about the endo- or
      exogeneity of the covariates and the functional form of the association with the
      outcome, and illustrate and evaluate consequences of violations of those
      assumptions using simulation studies and two real data examples.

PMID- 29069969
TI  - Model extension, calibration and validation of partial nitritation-anammox
      process in moving bed biofilm reactor (MBBR) for reject and mainstream
      wastewater.
AB  - In the paper, the extension of mathematical model of partial nitritation-anammox
      process in a moving bed biofilm reactor (MBBR) is presented. The model was
      calibrated with a set of kinetic, stoichiometric and biofilm parameters, whose
      values were taken from the literature and batch tests. The model was validated
      with data obtained from: laboratory batch experiments, pilot-scale MBBR for a
      reject water deammonification operated at Himmerfjarden wastewater treatment and
      pilot-scale MBBR for mainstream wastewater deammonification at Hammarby
      Sjostadsverk research facility, Sweden. Simulations were conducted in AQUASIM
      software. The proposed, extended model proved to be useful for simulating of
      partial nitritation/anammox process in biofilm reactor both for reject water and
      mainstream wastewater at variable substrate concentrations (influent total
      ammonium-nitrogen concentration of 530 +/- 68; 45 +/- 2.6 and 38 +/- 3 gN/m3 -
      for reject water - and two cases of mainstream wastewater treatment,
      respectively), temperature (24 +/- 2.8; 15 +/- 1.1 and 18 +/- 0.5 degrees C), pH
      (7.8 +/- 0.2; 7.3 +/- 0.1 and 7.4 +/- 0.1) and aeration patterns (continuous
      aeration and intermittent aeration with variable dissolved oxygen concentrations
      and length of aerated and anoxic phases). The model can be utilized for
      optimizing and testing different operational strategies of deammonification
      process in biofilm systems.

PMID- 29069970
TI  - First report of OXA-48-producing Escherichia coli in Croatia and confirmed
      intergenic transfer of a plasmid-carrying blaOXA-48 from Klebsiella pneumoniae.

PMID- 29069971
TI  - Benefits of a peer-led mock-OSCE.

PMID- 29069973
TI  - Delivering diversity.

PMID- 29069972
TI  - Angiotensin-converting enzyme activity and inhibition in dogs with cardiac
      disease and an angiotensin-converting enzyme polymorphism.
AB  - OBJECTIVE: The objective of this study was to evaluate angiotensin-converting
      enzyme (ACE) activity in dogs and with and without an ACE polymorphism in the
      canine ACE gene, before and after treatment with an ACE inhibitor. METHODS:
      Thirty-one dogs (20 wild-type, 11 ACE polymorphism) with heart disease were
      evaluated with ACE activity measurement and systolic blood pressure before and
      after administration of an ACE inhibitor (enalapril). RESULTS: Median pre
      treatment ACE activity was significantly lower for ACE polymorphism dogs than for
      dogs with the wild-type sequence ( P=0.007). After two weeks of an ACE inhibitor,
      ACE activity was significantly reduced for both genotypes (wild-type, P<0.0001;
      ACE polymorphism P=0.03); mean post-therapy ACE activity was no different between
      the groups. CONCLUSION: An ACE polymorphism is associated with lower levels of
      ACE activity. Dogs with the polymorphism still experience suppression of ACE
      activity in response to an ACE inhibitor. It is possible that the genetic status
      and ACE activity of dogs may impact the response of dogs with this variant to an
      ACE inhibitor.

PMID- 29069974
TI  - Body dysmorphic disorder and its associated psychological and psychopathological
      features in an Italian community sample.
AB  - OBJECTIVE: Body Dysmorphic Disorder (BDD) is a psychiatric condition
      characterized by preoccupation with perceived defects in physical appearance that
      are not observable or appear slight to others, along with low self-esteem, high
      perfectionism, and high comorbidity. Little is known about BDD prevalence and
      phenomenology in the Italian context, and no data are currently available on BDD
      prevalence using DSM-5 criteria in the Italian context. The aims of the current
      study were to explore the prevalence and the phenomenology of BDD and its
      associated psychological and psychopathological features such as self-esteem,
      perfectionistic traits, social anxiety, depressive, and obsessive-compulsive
      symptoms in a community sample. METHODS: Six hundred and fifteen community
      individuals completed a battery of self-report questionnaires. RESULTS: 10
      (1.63%) individuals met DSM-5 diagnostic criteria for BDD; hair, nose and teeth
      were the most common areas of concern. Individuals with BDD reported also lower
      levels of self-esteem, more severe social anxiety symptomatology, general
      distress, depression and obsessive-compulsive features than people without BDD.
      CONCLUSIONS: BDD is not a rare condition in the Italian context and it emerged to
      be associated with significant morbidity.

PMID- 29069975
TI  - The combination of escitalopram and aripiprazole: Investigation of psychomotor
      effects in rats.
AB  - Pre-clinical and clinical evidence suggests that the antidepressant efficacy of
      the selective serotonin reuptake inhibitor escitalopram can be enhanced by the
      dopamine and serotonin partial agonist aripiprazole. Given the range of possible
      neurochemical interactions between these drugs, the current study investigated
      whether aripiprazole alters the hedonic and psychomotor effects of escitalopram.
      Male Sprague Dawley rats ( n=116) received 10 mg/kg/day escitalopram
      (subcutaneous), 2 mg/kg/day aripiprazole (subcutaneous), or combined aripiprazole
      + escitalopram, and were tested for consumption of incentive nutritional stimuli
      (high-fructose corn syrup and chow), stereotypy and locomotor activity. At the
      conclusion of behavioral testing, mRNAs of two genes involved in reward processes
      were quantified: hypothalamic pro-opiomelanocortin and hippocampal brain-derived
      neurotrophic factor. Escitalopram produced a selective, but temporary, decrease
      in high fructose corn syrup consumption that was not altered by aripiprazole co
      administration. Escitalopram had no significant effect on locomotion, but
      aripiprazole co-administration produced a persistent increase in stereotypy. Both
      brain-derived neurotrophic factor and pro-opiomelanocortin mRNA levels were lower
      in the aripiprazole + escitalopram group relative to the escitalopram group.
      Taken together, these results suggest that aripiprazole may enhance the
      antidepressant efficacy of escitalopram through improvement of psychomotor
      functions.

PMID- 29069976
TI  - Twelve tips for applying change models to curriculum design, development and
      delivery.
AB  - Drawing primarily from business and management literature and the authors'
      experience, these 12 tips provide guidance to organizations, teams, and
      individuals involved in curriculum or program development at undergraduate,
      postgraduate, and continuing education levels. The tips are based around change
      models and approaches and can help underpin successful curriculum review,
      development, and delivery, as well as fostering appropriate educational
      innovation. A range of tools exist to support systematic program development and
      review, but even relatively simple changes need to take account of many factors,
      including the complexity of the environment, stakeholder engagement, cultural and
      psychological aspects, and the importance of followers.

PMID- 29069977
TI  - Comparison of periodontal inflammatory parameters among habitual gutka-chewers
      and naswar-dippers: a split-mouth retrospective clinical study.
AB  - OBJECTIVE: The aim of the present split-mouth retrospective study was to compare
      the clinical periodontal parameters among gutka-chewers and naswar-dippers.
      METHODS: A structured questionnaire was used to record demographic information.
      Jaw quadrant in which, gutka or naswar were placed were defined as "test-sites".
      The remaining jaw quadrants were designated as "control-sites". Clinical [plaque
      index (PI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical
      attachment loss (CAL)] and radiographic [alveolar bone loss (ABL)] parameters
      were compared among gutka-chewers and naswar-dippers in the test- and control
      sites. Data were analysed using non-parametric Wilcoxon signed rank test followed
      by post hoc analyses with the Bonferroni correction. p < .05 were considered
      statistically significant. RESULTS: Seventy-five gutka-chewers and 72 naswar
      dippers with mean ages of 45.2 +/- 0.8 years and 47.3 +/- 2.8 years, respectively
      were included. Gutka-chewers and naswar-dippers were consuming their respective
      smokeless tobacco product 10.2 times and 8.5 times daily for 15.1 +/- 2.7 and
      12.3 +/- 3.4 years, respectively. Among gutka-chewers and naswar-dippers, scores
      of PI, BOP, PPD >=4 mm, CAL and ABL were significantly higher in the test-sites
      compared with their respective control-sites (p < .01). CONCLUSIONS: Periodontal
      inflammatory parameters were poorer in the test-sites among gutka-chewers and
      naswar-dippers compared with the control-sites.

PMID- 29069978
TI  - Assessment of de novo copy-number variations in Italian patients with
      schizophrenia: Detection of putative mutations involving regulatory enhancer
      elements.
AB  - OBJECTIVES: Variants appearing de novo in genes regulating key neurodevelopmental
      processes and/or in non-coding cis-regulatory elements (CREs), as enhancers, may
      increase the risk for schizophrenia. However, CREs involvement in schizophrenia
      needs to be explored more deeply. METHODS: We investigated de novo copy-number
      variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of
      schizophrenia probands by using the Enhancer Chip, a customised array CGH able to
      investigate the whole genome with a 300-kb resolution, specific disease loci at a
      ten-fold higher resolution, and which was highly enriched in probes in more than
      1,250 enhancer elements selected from Vista Enhancer Browser. RESULTS: In seven
      patients, we found de novo CNVs, two of which overlapped VISTA enhancer elements.
      De novo CNVs encompass genes (CNTNAP2, MAGI1, TSPAN7 and MET) involved in brain
      development, while that involving the enhancer element hs1043, also includes
      ZIC1, which plays a role in neural development and is responsible of behavioural
      abnormalities in Zic mutant mice. CONCLUSIONS: These findings provide further
      evidence for the involvement of de novo CNVs in the pathogenesis of schizophrenia
      and suggest that CNVs affecting regulatory enhancer elements could contribute to
      the genetic vulnerability to the disorder.

PMID- 29069979
TI  - Enhanced degradation of carbon tetrachloride by sodium percarbonate activated
      with ferrous ion in the presence of ethyl alcohol.
AB  - In this study, the degradation performance of carbon tetrachloride (CT) by sodium
      percarbonate (SPC) activated with Fe(II) in the presence of ethyl alcohol (EA)
      was investigated. The experimental results showed that CT could be readily
      degraded and the optimal EA/Fe(II)/SPC/CT molar ratio for CT reduction was
      100/50/20/1. Superoxide radical anion ([Formula: see text]) and hydroxyethyl
      radical (*CHCH3OH, HER) were the predominant radical species responsible for CT
      degradation and EA could regulate the generation of [Formula: see text] and HER
      in the system. Further investigation for the solution matrix effects suggested
      that Cl-, [Formula: see text], [Formula: see text], and humic acid had negligible
      influences on CT degradation, while [Formula: see text] had negative effect in
      EA/Fe(II)/SPC system. On the other hand, the application of SPC/Fe(II)/EA
      technique is favorable to acidic condition is effective at a wide pH range of 3.0
      7.0. In summary, CT degradation in Fe(II)-activated SPC system can be
      significantly promoted by addition of solvents, and these findings provide an
      innovative technology for the degradation of highly oxidized organic
      contaminants.

PMID- 29069980
TI  - Immunotherapeutic effect of BCG-polysaccharide nucleic acid powder on
      Mycobacterium tuberculosis-infected mice using microneedle patches.
AB  - Polysaccharide nucleic acid fractions of bacillus Calmette-Guerin, termed BCG
      PSN, have traditionally been used as immunomodulators in the treatment of
      dermatitis and allergic diseases. While the sales of injectable BCG-PSN have
      shown steady growth in recent years, no reports of using BCG-PSN powder or its
      immunotherapeutic effects exist. Here, BCG-PSN powder was applied directly to the
      skin to evaluate the immunotherapeutic effects on mice infected with
      Mycobacterium tuberculosis (MTB). In total, 34 MUg of BCG-PSN powder could be
      loaded into a microneedle patch (MNP). Mice receiving BCG-PSN powder delivered
      via MNP exhibited significantly increased IFN-gamma and TNF-alpha production in
      peripheral blood CD4 + T cells and improved pathological changes in their lungs
      and spleens compared to control group mice. The immunotherapeutic effect of BCG
      PSN powder delivered via MNP was better than that delivered via intramuscular
      injection to some extent. Furthermore, MNPs eliminate the side effects of
      syringes, and this study demonstrated that BCG-PSN can be clinically
      administrated in powder form.

PMID- 29069981
TI  - Variables Associated With the Subjective Experience of Coercive Measures in
      Psychiatric Inpatients: A Systematic Review.
AB  - OBJECTIVE: This systematic review presents evidence regarding factors that may
      influence the patient's subjective experience of an episode of mechanical
      restraint, seclusion, or forced administration of medication. METHOD: Two authors
      searched CINAHL, PubMed, SCOPUS, Web of Science, and Psych-Info, considering
      published studies between 1 January 1992 and 1 February 2016. Based on the
      inclusion criteria and methodological quality, 34 studies were selected,
      reporting a total sample of 1,869 participants. RESULTS: The results showed that
      the provision of information, contact and interaction with staff, and adequate
      communication with professionals are factors that influence the subjective
      experience of these measures. Humane treatment, respect, and staff support are
      also associated with a better experience, and debriefing is an important
      procedure/technique to reduce the emotional impact of these measures. Likewise,
      the quality of the working and physical environment and some individual and
      treatment variables were related to the experience of these measures. There are
      different results in relation to the most frequently associated experiences and,
      despite some data that indicate positive experiences, the evidence shows such
      experiences to be predominantly negative and frequently with adverse
      consequences. It seems that patients find forced medication and seclusion to be
      more tolerable than mechanical restraint and combined measures. CONCLUSIONS: It
      appears that the role of the staff and the environmental conditions, which are
      potentially modifiable, affect the subjective experience of these measures. There
      was considerable heterogeneity among studies in terms of coercive measures
      experienced by participants and study designs.

PMID- 29069982
TI  - Electroconvulsive Therapy Practice in the Province of Quebec: Linked Health
      Administrative Data Study from 1996 to 2013.
AB  - OBJECTIVE: As part of a quality improvement process, we propose a model of
      routinely monitoring electroconvulsive therapy (ECT) in Canadian provinces using
      linked health administrative databases to generate provincial periodic reports,
      influence policy, and standardise ECT practices. METHODS: ECT practice in Quebec
      was studied from 1996 to 2013, using longitudinal data from the Quebec Integrated
      Chronic Disease Surveillance System of the Institut National de Sante Publique du
      Quebec, which links 5 health administrative databases. The population included
      all persons, aged 18 y and over, eligible for the health insurance registry, who
      received an ECT treatment at least once during the year. RESULTS: Among recorded
      cases, 75% were identified by physician claims and hospitalisation files, 19%
      exclusively by physician claims, and 6% by hospitalisation files. From 1996 to
      2013, 8,149 persons in Quebec received ECT with an annual prevalence rate of 13
      per 100,000. A decline was observed, which was more pronounced in women and in
      older persons. On average, each patient received 9.7 treatments of ECT annually.
      The proportion of acute ECT decreased whereas maintenance treatment proportions
      increased. A wide variation in the use of ECT was observed among regions and
      psychiatrists. CONCLUSION: This study demonstrates the profitable use of
      administrative data to monitor ECT use in Quebec, and provides a reliable method
      that could be replicated in other Canadian provinces. Although Quebec has one of
      the lowest utilisation rates reported in industrialized countries, regional
      disparities highlighted the need for a deeper examination of the quality and
      monitoring of ECT care and services.

PMID- 29069983
TI  - Short-term and long-term efficacy of classical ketogenic diet and modified Atkins
      diet in children and adolescents with epilepsy: A systematic review and meta
      analysis.
AB  - OBJECTIVES: Classical ketogenic diet (KD) and modified Atkins diet (MAD) are two
      types of KD commonly used for the treatment of intractable epilepsy throughout
      the world. Studies have shown the efficacy of these diets. However, no systematic
      review and meta-analysis study has to date compared the efficacy of KD and MAD in
      a time trend. Therefore, the objectives of the present study were to compare the
      short-term and long-term efficacy of classical KD and MAD in children and
      adolescents with epilepsy and to determine the efficacy of classical KD and MAD
      at multiple time points and in a time trend. METHODS: Main electronic literature
      databases, including MEDLINE/PubMed, Web of Science, Scopus, and EMBASE, were
      searched in November 2016. Rate difference and random effects model were used to
      compare the efficacy of the classical KD and MAD. RESULTS: Overall, 70 studies
      were eligible for inclusion. Meta-analysis revealed a non-significant trend
      toward a higher efficacy of MAD at month-3 and month-6 (P > 0.05). In the
      classical KD group, the percentage of responder patients achieving >=50% seizure
      reduction was 62, 60, 52, 42, and 46% at month-1, 3, 6, 12 and 24 and for the MAD
      group was 55, 47, 42, and 29% at month-1, 3, 6, and 12, respectively. DISCUSSION:
      Classical KD does not differ substantially from MAD in >=50% and >=90% reduction
      of seizure frequency at month-3 and month-6. Overall, the number of patients
      achieving seizure freedom increases over time.

PMID- 29069985
TI  - Neural autoantibodies in patients with neurological symptoms and histories of
      chemical/mold exposures.
AB  - A number of studies have linked exposures to industrial and household chemicals
      and biological toxins to increased risk of autoimmunity in general and elevated
      levels of autoantibodies to neural antigens specifically. Elevated neural
      autoantibodies are biomarkers for many diseases such as multiple sclerosis and
      Parkinson's disease. Our study reports levels of six types of neural
      autoantibodies in a group of 24 toxicant-exposed patients. The patients were
      exposed to a variety of toxicants including contaminated drinking water (four
      patients), building water/mold damage (eight patients), pesticides (four
      patients), and other assorted toxic chemicals (eight patients). Levels of all six
      neural autoantibodies were significantly elevated in most patients and in the
      patient group at large, with mean antibody levels for the 24 chemically exposed
      patients (relative to a healthy control population), in descending order: 475%
      for tau proteins, 391% for microtubule associated proteins-2, 334% for
      neurofilament proteins (NFP), 302% for myelin basic protein, 299% for glial
      fibrillary acidic proteins, and 225% for tubulin. Tau protein autoantibodies were
      significantly elevated in the patient groups with peripheral neuropathy, muscle
      and joint pain, asthma, and chemical sensitivity. Autoantibodies to tubulin were
      significantly higher in the chemical sensitivity and asthma patients,
      autoantibodies to NFP were significantly higher in the patients with sleep apnea,
      whereas S-100B autoantibodies were significantly increased in patients with
      muscle/joint pain, asthma, and apnea/insomnia. In patients exposed to
      environmental toxicants, measurements of autoantibodies may be useful for
      prevention, diagnosis, and treatment. This study adds to the scientific
      literature the ability of a broad spectrum of environmental triggers adversely
      affecting the nervous system through the process of autoimmunity, which may
      explain the increasing incidence of neurodegenerative diseases.

PMID- 29069986
TI  - Chromium oxide nanoparticle-induced biochemical and histopathological alterations
      in the kidneys and brain of Wistar rats.
AB  - Chromium oxide nanoparticles (Cr2O3 NPs) have a wide range of applications in
      industry. They are used as pigments, catalysts, wear-resistant or high
      temperature-resistant coating material and are used in liquid crystal displays.
      In view of ever escalating use of NPs, risk assessment becomes obligatory to
      ensure the safety of both human health and the ecosystem. The present study was
      designed and conducted to evaluate biochemical changes and histopathological
      alterations in kidneys and brain of rats, following exposure to Cr2O3 NPs. Male
      Wistar rats were divided into low-dose (50 ug/100 g body weight (bwt) groups and
      high-dose (200 ug/100 g bwt) groups. Each group type received oral administration
      of Cr2O3 NPs for multiple durations (single dosing, once daily for 7 days and
      once daily for 14 days, respectively). According to our data, this allotment
      presented a meaningful picture of NPs behaviour in different scenarios. In the
      kidneys and brain of Cr2O3 NPs-exposed animals, reactive oxygen species (ROS)
      production caused a significant increase in malondialdehyde (MDA) concentration
      along with a significant decrease in superoxide dismutase and glutathione levels,
      as compared to controls. Histopathological changes in these organs confirmed
      cellular injury and functional damage due to exposure to Cr2O3 NPs. In this
      study, we have distinguished pathological alterations consequent to deleterious
      oxidative stress due to enhanced ROS generation after Cr2O3 NPs exposure.

PMID- 29069984
TI  - Treatment of acute myocardial infarction in the sub-arctic region of Norway. Do
      we offer an equal quality of care?
AB  - Patients, relatives, healthcare workers and administrators are concerned about
      the quality of care offered. We aimed to explore the treatment of acute
      myocatrdial infarction (AMI) in Northern Norway, compare it with the national
      figures, and document whether there is an equal quality of care or not. The
      retrospective study included data on patients' treatment for AMI. The following
      sources were employed. The Norwegian Patient Registry, National Quality of Care
      Database, Norwegian Myocardial Infarction Registry and data from the National Air
      Ambulance Services of Norway. The period 2012-2014/15 was studied and the
      variables were: incidence of AMI, gender and age adjusted rates of AMI and
      revascularization (PCI, CABG) based on patient's place of living (according to
      hospital catchment area) and 30-day survival rate. The annual incidence of AMI
      was 9% higher in the northern region. Significant incidence variations (2.7-5.9
      AMI/1000 inhabitants) between the hospitals' catchment areas were revealed. The
      30-day survival rate varied between 85.1-92.1% between hospitals. The variation
      in revascularization/AMI rate was 0.72-1.54. Air amublance services' availability
      varied through the day. In conclusion, significant variations in the AMI rate and
      an unequal service within the region was revealed.

PMID- 29069987
TI  - In vitro fertilization-frozen embryo transfer in a patient with cytochrome P450
      oxidoreductase deficiency: a case report.
AB  - Cytochrome P450 enzymes are required for the synthesis of cholesterol and steroid
      hormones. Cytochrome P450 oxidoreductase (POR) donates electrons to microsomal
      cytochrome P450 enzymes. POR deficiency (PORD) is a rare autosomal recessive
      disease. In patients with PORD, steroid hormone synthesis is disrupted, which can
      cause infertility. The objective of this study was to report on a case of in
      vitro fertilization-frozen embryo transfer (IVF-FET) in a patient with PORD. The
      patient's hormone (i.e. 17alpha-hydroxyprogesterone) and electrolyte levels were
      within normal ranges ordinarily. Upon controlled ovarian stimulation, follicle
      growth was normal, but serum estrogen and progesterone levels were low and high,
      respectively. The serum progesterone level was elevated after long-acting
      gonadotropin-releasing hormone agonist treatment, and an endometrial biopsy
      showed a change in the proliferative phase. Genetic tests detected homozygous
      mutations (c.976 T > G, p.Y326D) in exon 10 of the POR gene. The frozen embryo
      was transferred during the administration of hormone replacement therapy. No
      significant morphological or metabolic abnormalities were observed in the
      neonate. Our findings suggest that infertile women with normal hormone levels may
      have metabolic diseases such as PORD. Further studies are needed to determine the
      cause of these diseases and to assist pregnancy in such women.

PMID- 29069988
TI  - Bariatric surgery reduces fasting total fatty acids and increases n-3
      polyunsaturated fatty acids in morbidly obese individuals.
AB  - BACKGROUND: Obesity is a global pandemic leading to increased mortality and
      increased risk of cardiovascular disease. Bariatric surgery is an established
      treatment of obesity leading to weight loss and reduction of mortality. To
      further elucidate how bariatric surgery improves metabolic control, we explored
      the fatty acid (FA) profiles in morbidly obese subjects treated with lifestyle
      intervention and subsequent bariatric surgery. METHODS: The intervention group
      consisted of 34 morbidly obese patients scheduled for bariatric surgery and the
      control group of 17 non-obese patients scheduled for elective laparoscopic
      procedures. The intervention group had to undergo lifestyle changes
      preoperatively. Fasting blood samples were drawn at admission, after lifestyle
      intervention and 1 year after bariatric surgery. RESULTS: At admission, the
      morbidly obese patients had significantly higher levels of monounsaturated FAs
      (MUFAs) and lower levels of n-6 polyunsaturated FAs (PUFAs) and n-3 PUFAs than
      healthy controls (all p-values <.05). In the intervention group, there was a
      significantly lower level of total FAs after lifestyle intervention, and from
      admission to 1 year after surgical intervention (both, p < .05), primarily
      reflecting a lower proportion of saturated FAs (SFAs). Following bariatric
      surgery, but not after lifestyle changes, there was an increase in the proportion
      of n-3 PUFA (p < .05) reaching levels not significantly different from healthy
      controls. CONCLUSIONS: Our findings suggest that a reduced proportion of the
      proposed anti-atherogenic n-3 PUFAs characterizes morbidly obese individuals, and
      that this FA profile is reversed by bariatric surgery, but not by lifestyle
      intervention.

PMID- 29069989
TI  - High first-trimester maternal blood cystatin C levels despite normal serum
      creatinine predict pre-eclampsia in singleton pregnancies.
AB  - Early biochemical identification of women at high risk for the development of pre
      eclampsia (PE) is still unsatisfactory. Renal markers measured during the first
      trimester were analysed to predict later occurrence of PE. A nested case-control
      study was conducted within the prospective predictive markers for the diagnosis
      of preeclampsia study. Pregnant women were included at the end of the first
      trimester and followed up until birth. Controls were matched to PE cases. Renal
      markers [i.e. creatinine, cystatin C (CysC), beta2 microglobulin (B2M), beta
      trace protein (BTP), glomerular filtration rate estimations (eGFR) of the
      aforementioned markers, uric acid (UA), urea, and serum uromodulin (sUMOD)] were
      compared to placental growth factor (PlGF), a marker known to predict PE later in
      pregnancy. Reference intervals were determined for the different markers. In the
      183 women (PE, n = 39; controls, n = 144), CysC, the CysC/PlGF ratio (p < .01)
      and UA were higher, whereas the eGFRCysC/eGFRCrea ratio (a marker of glomerular
      endothelial integrity and shrunken pore syndrome) and PlGF were lower in women
      who developed PE (p < .05 for all). Compromised filtration of the larger molecule
      CysC together with a normal creatinine, in a subset of PE cases (15.3%) was a
      unique, strong and independent predictor of later PE if the baseline CysC
      concentration was >0.85 mg/l. In conclusion, CysC and its derivatives as well as
      UA, indicating volume expansion, measured at the end of the first trimester are
      predictive of PE. Thus, women can be easily identified and followed as an early
      reduction in glomerular filtration quality poses a high risk for a subsequent
      development of PE.

PMID- 29069992
TI  - Physical activity participation among families of children with visual
      impairments and blindness.
AB  - PURPOSE: Physical activity (PA) provides multiple benefits to children with
      visual impairments (VI) and their families. However, the empirical literature
      base is underdeveloped on how family PA experiences impact participation for
      children with VI. The purpose of this study was two-fold; that is: (a) to explore
      why families with children with VI seek out and participate in PA, and (b) to
      describe the strategies and supports needed by families of children with VI to
      improve PA participation. METHOD: The research method was descriptive-qualitative
      positioned in the theoretical framework of the theory of planned behavior.
      Participants were parents of children with VI (n = 10) who took part in one-on
      one semi-structured telephone interviews. Interview recordings were transcribed
      and analyzed using a thematic line-by-line analysis. RESULTS: Three salient,
      recurrent, and interrelated themes emerged from the data analyses. These themes
      were: (a) committed, (b) challenged, and (c) access. CONCLUSIONS: Findings
      revealed that parents valued PA, but they lacked the skills to teach and advocate
      for their children regarding PA. As a consequence, parents voiced the need for a
      support system that would allow their families to be more physically active.
      Implications for Rehabilitation Results of this study demonstrated that parents
      valued physical activity, but they lacked the skills necessary to confidently
      engage their children in physical activity. Physical activity interventions are
      needed to enhance the quality of life of children with visual impairments and
      their families. Physical activity programs and interventions are most likely to
      enhance intentions to engage in physical activity among children with visual
      impairments and their parents. Results demonstrated that parents of children with
      visual impairments were interested to work side-by-side with physical activity
      professionals to enhance recreational physical activity opportunities available
      to their children.

PMID- 29069993
TI  - Analyses of the relationship between a 'number of reflux episodes' exceeding 70
      and the pH index in neurologically impaired children by evaluating esophageal
      combined pH-multichannel intraluminal impedance measurements.
AB  - BACKGROUND: The present study aimed to evaluate the characteristics associated
      with a number of reflux episodes (NoRE) of 70 by comparing the clinical and
      multichannel intraluminal impedance pH measurements (pH/MII) and pH index (pHI)
      in neurologically impaired (NI) children. PATIENTS AND METHODS: NI children (1-16
      years of age) in whom pH/MII had been measured for GERD study were enrolled in
      this study. All children were divided into NoRE >70 or <=70 and pHI >4.0 or
      <=4.0, >5.0 or <=5.0 or >7.0 or <=7.0. In addition, the NI children with pHI
      >4.0, >5.0 and >7.0 were subdivided into NoRE >70 and <=70 groups. The clinical
      and pH/MII measurements were compared between each of the two groups. The cutoff
      values of pHI and baseline impedance (BI) (Z6) were calculated to discriminate
      NoRE >70 and <=70. RESULTS: A total of 61 NI children were enrolled in this
      study. There was a significant difference in the acid-related parameters, the
      NoRE (nonacid) and BI between NoRE >70 and <=70, acid-related parameters and BI
      between pHI >4.0 and <=4.0, >5.0 and <=5.0 and >7.0 and <=7.0 groups.
      Furthermore, a significant difference was still observed in the BI between NoRE
      >70 and <=70 groups among patients with pHI >4.0, >5.0 or >7.0. The cutoff values
      of pHI and BI (Z6) for discriminating NoRE >70 and <=70 were 9.2 and 1049Omega,
      respectively. CONCLUSION: The present study indicates that NoRE 70 corresponds to
      GERD in which patients suffer severe acid exposure with pH of around 9% and
      esophageal mucosal damage with low BI value in NI children.

PMID- 29069994
TI  - Protective effects of gallic acid against methotrexate-induced toxicity in rats.
AB  - BACKGROUND: Methotrexate, as a chemotherapy drug, can cause chronic liver damage
      and oxidative stress. Aim of this study was to evaluate the preventive effect of
      gallic acid (GA) on methotrexate (MTX)-induced oxidative stress in rat liver.
      METHODS: Twenty-eight male rats were randomly divided into four groups as
      control, MTX (20 mg/kg, i.p.), MTX + GA (30 mg/kg/day, orally) and GA treated.
      Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline
      phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury.
      Malondialdehyde (MDA) and glutathione (GSH) levels and hepatic antioxidant
      enzymes activities including catalase (CAT), superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) were assayed in liver tissue. The expression of SOD2
      and GPx1 genes were evaluated by real-time RT-PCR and liver histopathology was
      evaluated by light microscopy. RESULTS: The result obtained from current study
      showed that GA remarkably reduced MTX-induced elevation of AST, ALT and ALP and
      increased MTX-induced reduction in GSH content, GPx, CAT and SOD activity as well
      as GPx1 and SOD2 gene expressions. Histological results showed that MTX led to
      liver damage and GA could improve histological changes. CONCLUSIONS: Our results
      indicate that GA ameliorates biochemical and oxidative stress parameters in the
      liver of rats exposed to MTX.

PMID- 29069995
TI  - PRO-C3: a new and more precise collagen marker for liver fibrosis in patients
      with chronic hepatitis C.
AB  - OBJECTIVE: Detecting significant fibrosis and cirrhosis remains important in
      treatment and follow-up of patients with chronic hepatitis C Infection (CHC). The
      aim of this study was to assess the ability of PRO-C3 to identify significant
      fibrosis (Ishak score >=3) and cirrhosis (Ishak score >=5) both as a single test
      and as a part of algorithms. MATERIALS AND METHODS: PRO-C3 was assessed in
      baseline samples from the NORDynamIC trial. 270 patients were stratified into
      groups according to baseline biopsy. Baseline APRI, FIB-4 and GUCI scores were
      available for comparison in 232 patients. RESULTS: PRO-C3 increased with Ishak
      scores (p = .001). Area under the curve (AUC) for significant fibrosis was 0.75
      (95% CI 0.68-0.81) and 0.76 (95% CI 0.68-0.84) for cirrhosis. FIB-4, APRI and
      GUCI had similar AUCs. In a PRO-C3 algorithm including age, platelet count, body
      mass index (BMI) and international normalised ratio (INR), the diagnostic
      efficacy improved to 0.85 (CI 0.80-0.89) and 0.90 (IQR 0.84-0.96) for significant
      fibrosis and cirrhosis, respectively. CONCLUSIONS: In our study, PRO-C3 was an
      independent predictor of fibrosis stage, and may play an important role in
      managing CHC patients.

PMID- 29069997
TI  - Correction to: M. Johansson et al., Psychometric testing of a Swedish version of
      the Apathy Evaluation Scale.

PMID- 29069996
TI  - Transporting carriers for intracellular targeting delivery via non-endocytic
      uptake pathways.
AB  - To develop novel therapies for clinical treatments, it increasingly depends on
      sophisticated delivery systems that facilitate the drugs entry into targeting
      cells. Profound understanding of cellular uptake routes for transporting carriers
      promotes the optimization of performance in drug delivery systems. Although
      endocytic pathway is the most important part of cellular uptake routes for many
      delivery systems, it suffers the trouble of enzymatic degradation of transporting
      carriers trapped in endosomes/lysosomes. Therefore, it is desirable to develop
      alternative transporting methods for delivery systems via non-endocytic pathways
      to achieve more effective intracellular delivery. In this review, we summarize
      the literature exploring transporting carriers that mediate intracellular
      delivery via non-endocytic pathways to present the current research status in
      this field. Cell-penetrating peptides, pH (low) insertion peptides, and
      nanoparticles are categorized to exhibit their ability to directly transport
      various cargos into cytoplasm via non-endocytic uptake in different cell lines.
      It is hoped that this review can spur the interesting on development of drug
      delivery systems via non-endocytic uptake pathway.

PMID- 29069998
TI  - Composite Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia and Follicular
      Lymphoma: A Clinicopathological Study of Six Cases.
AB  - BACKGROUND: Composite small lymphocytic lymphoma/chronic lymphocytic leukemia
      (SLL/CLL) and follicular lymphoma (FL) is extremely rare, and only 13 cases have
      been reported previously. METHODS: We identified 6 cases of composite SLL/CLL and
      FL in our database and studied their clinical, histologic, immunophenotypic, and
      cytogenetic features. A literature review of the existing cases was also
      conducted. RESULTS: The patients included 4 males and 2 females, with a median
      age of 72 years. Four patients presented with lymphadenopathy and 2 with
      extranodal diseases. Lymphocytosis was seen in 2 cases. Serum lactate
      dehydrogenase levels were within normal range in all but one case. There were 2
      histologic patterns: SLL/CLL predominant pattern (type I) and FL predominant or
      mixed pattern (type II). The type I pattern was exclusively associated with in
      situ follicular neoplasia (ISFN). The SLL/CLL showed typical morphology and
      immunophenotype in all the cases. The FL component included low grade (n = 3),
      ISFN (n = 2), and primary cutaneous FL (n = 1). Four cases had staging bone
      marrow biopsies including 3 cases with involvement by SLL/CLL and 1 case with
      involvement by SLL/CLL and FL. Four patients received treatments, one was under
      clinical surveillance, and one had no available information. All patients were
      alive after a median follow-up of 22 months. CONCLUSIONS: This is the largest
      case serial of composite SLL/CLL and FL. The CL affects elderly individuals,
      presents with advanced clinical stage, and appears to have a relatively indolent
      clinical course.

PMID- 29069999
TI  - Use of hormone therapies in disseminated carcinomatosis of the bone marrow
      associated with hormone receptor-positive breast cancer.
AB  - Disseminated carcinomatosis of the bone marrow (DCBM) is diffusely invasive bone
      metastasis resulting from solid tumors. DCBM is often associated with
      disseminated intravascular coagulation (DIC) or hemolytic anemia. Generally, DCBM
      treatment includes cytotoxic chemotherapy for underlying solid tumors and
      management of hematological conditions if present. We report a case of DCBM
      accompanied with DIC in hormone receptor-positive breast cancer. Due to her life
      threatening condition, we used hormone therapies, not cytotoxic chemotherapies,
      to treat her DCBM. With zoledronic acid, her DIC and general condition gradually
      improved and eventually she could return to her daily life. If DCBM occurs in
      hormone receptor-positive breast cancer, hormone therapy can be one of the
      treatment choices.

PMID- 29070000
TI  - We are not the same people we used to be: An exploration of family biographical
      narratives and identity change following traumatic brain injury.
AB  - Subjective changes are increasingly recognised as important in recovery and
      rehabilitation following traumatic brain injury. Accumulation of subjective
      changes over time has led many to examine the question of "continuity of self"
      post-injury. Vacillation between feeling the same and different is common and
      often at odds with the medical narrative preparing families for permanent change.
      This position of ambiguity was examined in a qualitative narrative study. The aim
      of this paper is to describe the narrative structures used by uninjured members
      of a family to understand change. These changes relate primarily, to their
      perspective of whether and how the injured person had changed, but also
      secondarily to whether and why they themselves felt they had changed in the first
      year post-injury. Nine uninjured family members from three families took part in
      three unstructured interviews during the first twelve months post-injury. In
      depth narrative analysis showed family members used biographical attendance;
      biographical disruption; biographical continuity; and biographical reconstruction
      to understand change. Drawing on these findings it is argued that concentrating
      on a narrative of change is too limiting and that engaging in biographical
      narratives may help humanise care provided to injured individuals and their
      families. Implications for research and practice are discussed.

PMID- 29070001
TI  - How to formulate research questions and design studies for telehealth assessment
      and evaluation.
AB  - Planning a research strategy and formulating the right research questions at
      various stages of developing a telehealth intervention are essential for
      producing scientific evidence. The aim of research at each stage should
      correspond to the maturity of the intervention and will require a variety of
      study designs. Although there are several published evaluation frameworks for
      telemedicine or telehealth as a subset of broader eHealth domain, there is
      currently no simple model to guide research planning. In this paper we propose a
      five-stage model as a framework for planning a comprehensive telehealth research
      program for a new intervention or service system. The stages are: (1) Concept
      development, (2) Service design, (3) Pre-implementation, (4) Implementation, (5)
      Post-implementation, and at each stage a number of studies are considered. Robust
      evaluation is important for the widespread acceptance and implementation of
      telehealth. We hope this framework enables researchers, service administrators
      and clinicians to conceptualise, undertake and appraise telehealth research from
      the point of view of being able to assess how applicable and valid the research
      is for their particular circumstances.

PMID- 29070002
TI  - Research methods and methodology in telemedicine.

PMID- 29070003
TI  - Pitfalls in studies of eosinopenia and neutrophil-to-lymphocyte count ratio.
AB  - There is a number of publications evaluating the eosinophil count and the
      neutrophil-to-lymphocyte count ratio for diagnosis, prognosis or monitoring of
      patients. Of special interest is the use of these parameters for discrimination
      between the different causes of fever (e.g. bacterial versus viral vs. non
      infectious causes of fever) and for monitoring the efficacy of therapy and
      predict the course of the patient. However, pitfalls in previous study designs
      prevent applicability to clinical practice. Here, we provide a short review of
      the relevant literature and summarize important factors that should be taken into
      account when designing studies, with special attention to the selection of a
      proper and clinically meaningful study population and the effects of the stress
      response and of corticosteroids.

PMID- 29070004
TI  - Removal of Hg, As in FGD gypsum by different aqueous ammonia (amines) during CO2
      sequestration.
AB  - CO2 sequestration by flue gas desulfurization gypsum (FGDG) has become a
      promising FGDG disposal technology due to simultaneous CO2 emission reduction and
      FGDG conversion into calcium carbonate. In this paper, another merit of the novel
      technology, i.e., the removal of toxic elements (e.g., Hg and As) in FGDG, will
      be addressed for the first time. In three different aqueous ammonia (or amines)
      media, removal efficiencies of Hg and As in FGDG samples were evaluated during
      CO2 sequestration. Higher than 90% and 20% removal efficiencies, respectively,
      for Hg and As are achieved at 40 degrees C in aqueous ammonia media, but they
      decrease at elevated temperatures. Ammonia loss takes place at 80 degrees C and
      pH varies greatly with temperatures in aqueous ammonia. This is disadvantageous
      for the formation of Hg-ammonia complexes and for the yield of carbonates, which
      are responsible for Hg or As re-adsorption. The sequential chemical extraction
      method suggests that the speciation changes of Hg are induced by FGDG
      carbonation, and that unstable Hg speciation in triethanolamine increases at
      elevated temperatures.

PMID- 29070005
TI  - Cecal Endometriosis With Intestinal Metaplasia Misdiagnosed as Neoplasm of the
      Cecum by Intraoperative Histological Examination.
AB  - Appendiceal or cecal endometriosis with intestinal metaplasia is uncommon and may
      mimic mucinous tumors of the appendix. A 50-year-old woman was found incidentally
      to have an ileocecal lesion. In the intraoperative histological examination, a
      diagnosis of neoplasm of the cecum was made predominantly based on mucin
      extrusion with scattered lining mucinous epithelium. However, postoperative
      histological diagnosis of the lesion was cecal endometriosis with intestinal
      metaplasia as determined by thoroughly microscopic inspection and the presence of
      typical endometrial glands with surrounding endometrial-type stroma. There was no
      evidence of recurrence and pseudomyxoma peritonei after 1 year of follow-up.
      Overinterpretation of cytological atypia or mucin extrusion in endometriosis may
      lead to inappropriate surgical management. Therefore, in any ileocecal or
      appendiceal lesions with mucinous epithelia and mucin extrusions, removal of
      sufficient tissue from different portions of the lesion is essential for surgeons
      and pathologists to make a precise diagnosis in the intraoperative histological
      examination.

PMID- 29070006
TI  - Accelerated Long-Term Forgetting Limited to the Recollection Component of
      Recognition Memory in a Temporal Lobe Epileptic Patient.
AB  - Accelerated long-term forgetting (ALF) is a frequent finding in patients with
      temporal lobe epilepsy (TLE). Here we report the case of a TLE patient who
      complained of marked difficulties in remembering personal events and information
      even though repeated neuropsychological assessments had failed to detect any
      deficit on common laboratory memory tests. The patient underwent an experimental
      investigation that involved estimating recollection and familiarity processes in
      the performance on verbal and visual recognition tests, over intervals ranging
      from 10 minutes to 7 days. Results showed accelerated forgetting confined to the
      recollection component only, which was particularly evident in the verbal test.

PMID- 29070008
TI  - Editorial: "Phytochemicals for Human Diseases: An Update".

PMID- 29070007
TI  - Planning the location of facilities to implement a reverse logistic system of
      post-consumer packaging using a location mathematical model.
AB  - The implementation of reverse logistics systems (RLS) for post-consumer products
      provides environmental and economic benefits, since it increases recycling
      potential. However, RLS implantation and consolidation still face problems. The
      main shortcomings are the high costs and the low expectation of broad
      implementation worldwide. This paper presents two mathematical models to decide
      the number and the location of screening centers (SCs) and valorization centers
      (VCs) to implement reverse logistics of post-consumer packages, defining the
      optimum territorial arrangements (OTAs), allowing the inclusion of small and
      medium size municipalities. The paper aims to fill a gap in the literature on RLS
      location facilities that not only aim at revenue optimization, but also the
      participation of the population, the involvement of pickers and the service
      universalization. The results showed that implementation of VCs can lead to
      revenue/cost ratio higher than 100%. The results of this study can supply
      companies and government agencies with a global view on the parameters that
      influence RLS sustainability and help them make decisions about the location of
      these facilities and the best reverse flows with the social inclusion of pickers
      and serving the population of small and medium-sized municipalities.

PMID- 29070009
TI  - Editorial: New Therapetic Approaches in the Management of Ischemia Reperfusion
      Injury and Cardiometabolic Diseases: Opportunities and Challenges.

PMID- 29070010
TI  - Longitudinal study of gastroesophageal reflux and erosive tooth wear.
AB  - BACKGROUND: Approximately 60% of patients presenting to dentists with erosive
      tooth wear have significant gastroesophageal reflux (GERD), despite minor reflux
      symptoms. No longitudinal studies of reflux-associated erosive tooth wear and of
      reflux characteristics have been reported to date. The aim of this study was to
      characterize the longitudinal course of GERD and of associated erosive tooth
      wear, as well as factors predictive of its progression, in a large group of
      patients. METHODS: Seventy-two patients presenting to dentists with clinically
      significant erosive tooth wear and increased esophageal acid exposure by 24-h
      multichannel intraluminal pH-impedance measurement (MII-pH) were re-assessed
      clinically and by MII-pH after 1 year treatment with esomeprazole 20 mg twice
      daily. Predictive factors for erosive tooth wear were assessed by logistic
      regression. RESULTS: At follow-up, no further progression in erosive tooth wear
      was observed in 53 (74%) of patients. The percentage of time with a pH < 4, the
      number of acid reflux episodes and the percentage of proximal esophageal reflux
      off-PPI did not change significantly after one year, but the number of weakly
      acidic reflux episodes decreased significantly in the large subgroup without
      progression. None of the baseline demographic, clinical, endoscopic or esophageal
      acid exposure characteristics were significantly associated with progression of
      erosive tooth wear at follow-up. CONCLUSIONS: In this longitudinal study in
      patients with erosive tooth wear and oligosymptomatic GERD receiving esomeprazole
      for one year, erosive tooth wear did not progress further in the majority of
      patients. Background acidic esophageal reflux exposure appeared stable over time,
      whereas weakly acidic exposure decreased significantly in patients without
      erosion progression. MII-pH measurements on-PPI and with healthy controls will be
      useful in the further elucidation of the causal role of reflux in erosive tooth
      wear. TRIAL REGISTRATION: ClinicalTrials.gov , retrospectively registered:
      NCT02087345 .

PMID- 29070011
TI  - The obesity conundrum in sepsis.
AB  - While the long-term negative effects of obesity on health is a well-studied
      phenomenon, its effects on acute illnesses seem to be the contrary. Several
      studies have indicated the possibility of an 'obesity paradox' in sepsis - where
      overweight and obese patients have better outcomes than normal weight patients.
      These meta-analyses including large numbers of patients across different
      countries raised an interesting but debatable topic. Results from meta-analyses
      of observational studies should be interpreted with caution, and a prove of
      association not be mistaken as prove of causality. Limitations common to such
      studies include inadequate adjustment for confounding and selection bias. More
      rigorous investigations to clarify any causal relationship between obesity and
      mortality in sepsis are needed.

PMID- 29070012
TI  - Factors associated with the burden of family caregivers of patients with mental
      disorders: a cross-sectional study.
AB  - BACKGROUND: Caregivers are responsible for the home care of family members with
      mental-health disorders often experience changes in their life that can generate
      stress and burden. The aim of this study was to identify factors associated with
      the burden of caregivers of family members with mental disorders. METHODS: This
      cross-sectional study was conducted with a non-probability sample of family
      caregivers, whose patients attended a community services program, the
      Psychosocial Care Centers, in three cities in the southwest region of Goias
      State, Central Brazil. Data collection took place from June 2014 to June 2015.
      The participants were 281 caregivers who completed a sociodemographic
      questionnaire and the Zarit Burden Interview (ZBI). Bivariate analyses (t test,
      analysis of variance, and Pearson correlation) were performed, and variables with
      values of p < 0.10 and gender were included in a multiple-linear regression
      model. Values of p < 0.05 were considered significant. RESULTS: The caregivers
      were mostly female and parents of the patients, were married, with low education,
      and of low income. The mean ZBI score was 27.66. The factors independently
      associated with caregivers' burden were depression, being over 60 years of age,
      receiving no help with caregiving, recent patient crisis, contact days, and
      having other family members needing care. CONCLUSIONS: This study identified
      factors that deserve the attention of community services and can guide programs,
      such as family psycho-education groups, which may help to minimize or prevent the
      effects of burden on family caregivers responsible for patients' home care.

PMID- 29070013
TI  - p53 expression in patients with ulcerative colitis - associated with dysplasia
      and carcinoma: a systematic meta-analysis.
AB  - BACKGROUND: Tumor suppressor gene p53 expression has been reported in patients
      with ulcerative colitis (UC). However, the correlation between p53 expression and
      UC remains controversial. The aim of this meta-analysis was to investigate the
      association between p53 expression and different pathological types of UC.
      METHODS: Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and
      CNKI databases. The overall odds ratios (ORs) and their corresponding 95%
      confidence intervals (95% CIs) were summarized in this study. RESULTS: Final 19
      papers were identified in this meta-analysis, including 1068 patients with UC and
      130 normal tissue samples. Immunohistochemical p53 expression was significantly
      higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue
      samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR
      = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC
      with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group
      vs. normal tissues) showed that p53 expression was correlated with UC in Asians,
      but not in Caucasians. When UC with dysplasia was compared to UC group, p53
      expression was linked to UC with dysplasia among both Asians and Caucasians. When
      UC-CRC was compared to UC with dysplasia, p53 expression was not associated with
      UC-CRC in both Caucasians and Asians. CONCLUSIONS: p53 expression was closely
      associated with UC-CRC development. p53 expression showed different ethnic
      characteristics among different pathological types of UC.

PMID- 29070014
TI  - Lack of associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism
      (rs1799971) with alcohol dependence: review and meta-analysis of retrospective
      controlled studies.
AB  - BACKGROUND: Studies have sought associations of the opioid receptor mu 1 (OPRM1)
      A118G polymorphism (rs1799971) with alcohol-dependence, but findings are
      inconsistent. We summarize the information as to associations of rs1799971 (A >
      G) and the alcohol-dependence. METHODS: Systematically, we reviewed related
      literatures using the Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guideline. Embase, PubMed, Web of Knowledge, and Chinese
      National Knowledge Infrastructure (CNKI) databases were searched using select
      medical subject heading (MeSH) terms to identify all researches focusing on the
      present topic up to September 2016. Odds ratios (ORs) along with the 95%
      confidence interval (95% CI) were estimated in allele model, homozygote model,
      heterozygote model, dominant model and recessive model. Ethnicity-specific
      subgroup-analysis, sensitivity analysis, heterogeneity description, and
      publication-bias assessment were also analyzed. RESULTS: There were 17 studies,
      including 9613 patients in the present meta-analysis. The ORs in the 5 genetic
      models were 1.037 (95% CI: 0.890, 1.210; p = 0.64), 1.074 (95% CI: 0.831, 1.387;
      p = 0.586), 1.155 (95% CI: 0.935, 1.427; p = 0.181), 1.261 (95% CI: 1.008, 1.578;
      p = 0.042), 0.968 (95% CI: 0.758, 1.236; p = 0.793), respectively. An association
      is significant in the dominant model, but there is no statistical significance
      upon ethnicity-specific subgroup analysis. CONCLUSION: The rs1799971 (A > G) is
      not strongly associated with alcohol-dependence. However, there are study
      heterogeneities and limited sample sizes.

PMID- 29070015
TI  - Correction to: household preferences for reducing greenhouse gas emissions in
      four European high-income countries: does health information matter? A mixed
      methods study protocol.

PMID- 29070019
TI  - A 95 year-old suffering circulatory arrest after accidental hypothermia: a case
      report.
AB  - BACKGROUND: The elderly are vulnerable to cold and prone to accidental
      hypothermia, both because of environmental and endogenous factors. The incidence
      of severe accidental hypothermia among the elderly is poorly described, but many
      cases probably go unrecorded. Going through literature one finds few publications
      on severe hypothermia among the elderly, and, to our knowledge, nothing about
      extracorporeal re-warming of geriatric hypothermia victims. CASE PRESENTATION: We
      present a case were a 95 year-old man with severe accidental hypothermia and
      circulatory arrest was brought to our hospital under on-going CPR, and was
      successfully resuscitated with extracorporeal circulation. He was discharged to
      his home without physical sequelae a few weeks later. CONCLUSION: The decision
      whether or not to continue resuscitation of a nonagenarian can be difficult in
      many respects. Knowing that resuscitation with extracorporeal circulation is
      resource intensive may complicate the discussion. In light of our experience with
      this case we discuss medical and ethical aspects of modern treatment of severe
      accidental hypothermia.

PMID- 29070016
TI  - Investigating the epigenetic profile of the inflammatory gene IL-6 in late-life
      depression.
AB  - BACKGROUND: It is well established that there is a link between inflammation and
      depression, with several studies reporting increased circulating levels of the
      pro-inflammatory cytokine, interleukin-6 (IL6), in depressed individuals.
      Peripheral epigenetic marks, including DNA methylation, hold promise as
      biomarkers for a range of complex conditions, with potential to inform diagnosis
      and tailor interventions. The aim of this study was to determine whether
      individuals with depression display differential methylation of the IL6 gene
      promoter compared to individuals without depression. METHODS: The ESPRIT study of
      later life neuropsychiatric disorders used a random sampling framework to select
      non-institutionalised participants aged >=65 years and over living in the
      Montpellier region of France. Major depressive disorder (MDD) was assessed using
      the Mini International Neuropsychiatric Interview (MINI) according to DSM-IV
      criteria. High levels of depressive symptoms were defined as a score of >=16 on
      the Centre for Epidemiologic Studies Depression Scale (CES-D). IL6 promoter DNA
      methylation was measured on a sub-sample of 380 participants who provided buccal
      samples. RESULTS: Individuals with depression (current MDD or high depressive
      symptoms) had lower IL6 methylation levels at one of the four sites investigated,
      however the effect size was small (? 2.4%, SE 0.009, p = 0.006). Interestingly,
      antidepressant use was independently associated with higher IL-6 methylation at
      the same site (? 4.6%, SE 0.019, p = 0.015). In multivariate linear regression
      analyses adjusting for covariates, including sex and smoking status, these
      associations remained. There was no effect modification when considering IL6
      genotype. CONCLUSION: This study presents evidence that IL6 methylation may be a
      marker of depression status in older individuals, however further work is now
      needed to replicate these findings and to assess the association with
      inflammatory status of individuals.

PMID- 29070017
TI  - Postdiagnostic physical activity, sleep duration, and TV watching and all-cause
      mortality among long-term colorectal cancer survivors: a prospective cohort
      study.
AB  - BACKGROUND: Lifestyle recommendations for cancer survivors are warranted to
      improve survival. In this study, we aimed to examine the association of total
      physical activity, different types of physical activity, hours of sleeping at day
      and night, and hours spent watching television (TV) with all-cause mortality in
      long-term colorectal cancer (CRC) survivors. METHODS: We assessed physical
      activity in 1376 CRC survivors (44% women; median age, 69 years) at median 6
      years after CRC diagnosis using a validated questionnaire. Multivariable-adjusted
      Cox regression models were used to estimate hazard ratios (HRs) for all-cause
      mortality according to categories of physical activities, sleep duration, and TV
      watching. RESULTS: During a median follow-up time of 7 years, 200 participants
      had died. Higher total physical activity was significantly associated with lower
      all-cause mortality (HR: 0.53; 95% CI: 0.36-0.80, 4th vs. 1st quartile).
      Specifically, sports, walking, and gardening showed a significant inverse
      association with all-cause mortality (HR: 0.34; 95% CI: 0.20-0.59, HR: 0.65; 95%
      CI: 0.43-1.00, and HR: 0.62; 95% CI: 0.42-0.91, respectively for highest versus
      lowest category). Individuals with >=2 h of sleep during the day had a
      significantly increased risk of all-cause mortality compared to individuals with
      no sleep at day (HR: 2.22; 95% CI: 1.43-3.44). TV viewing of >=4 h per day
      displayed a significant 45% (95% CI: 1.02-2.06) higher risk of dying compared to
      <=2 h per day of watching TV. CONCLUSIONS: Physical activity was inversely
      related to all-cause mortality; specific activity types might be primarily
      responsible for this association. More hours of sleep during the day and a higher
      amount of TV viewing were each associated with higher all-cause mortality. Based
      on available evidence, it is reasonable to recommend CRC survivors to engage in
      regular physical activity.

PMID- 29070018
TI  - Hemorrhagic hypopyon as presenting feature of intravascular lymphoma, a case
      report.
AB  - BACKGROUND: Herpes uveitis has been previously reported to present with hyphema,
      but hemorrhagic hypopyon is rarely reported as a herpetic uveitis manifestation.
      We report a case of herpes simplex virus (HSV) presenting with hemorrhagic
      hypopyon, and speculate on the underlying pathophysiology with relation to an
      intravascular lymphoma which was subsequently diagnosed as a result. CASE
      PRESENTATION: We present a case wherein a 62-year-old Japanese rheumatoid
      arthritis woman, with HSV uveitis, presented with hemorrhagic hypopyon in the
      anterior chamber and a fever with photophobia. Patient was treated with antiviral
      drugs which improved the hyphema and corneal lesions, but lesions recurred 3
      months later. This rare presentation of HSV induced uveitis, and its subsequent
      recurrence, aroused suspicion of an additional hypopyon-inducing pathology. On
      account of previous history of lung opacities and elevated LDH, intravascular
      lymphoma was eventually diagnosed via lung biopsy. She was treated for the
      lymphoma which also completely resolved all ocular symptoms without any
      recurrence as of 1.5 years later. CONCLUSION: The exceedingly rare presentation
      of hemorrhagic hypopyon may have been enabled by an interaction of the HSV with
      the intravascular lymphoma. HSV involvement was indicated by the dendritic
      lesions, IgG assay, and response to anti-viral drugs. The ocular involvement of
      the intravascular lymphoma seems to be indicated by virtue of the anti-tumor
      drugs completely resolving all ocular symptoms.

PMID- 29070020
TI  - Schistosomiasis mansoni incidence data in Rwanda can improve prevalence
      assessments, by providing high-resolution hotspot and risk factors
      identification.
AB  - BACKGROUND: Schistosomiasis mansoni constitutes a significant public health
      problem in Rwanda. The nationwide prevalence mapping conducted in 2007-2008
      revealed that prevalence per district ranges from 0 to 69.5% among school
      children. In response, mass drug administration campaigns were initiated.
      However, a few years later some additional small-scale studies revealed the
      existence of areas of high transmission in districts formerly classified as low
      endemic suggesting the need for a more accurate methodology for identification of
      hotspots. This study investigated if confirmed cases of schistosomiasis recorded
      at health facility level can be used to, next to existing prevalence data, detect
      geographically more accurate hotspots of the disease and its associated risk
      factors. METHODS: A GIS-based spatial and statistical analysis was carried out.
      Confirmed cases, recorded at primary health facilities level, were combined with
      demographic data to calculate incidence rates for each of 367 health facility
      service area. Empirical Bayesian smoothing was used to deal with rate
      instability. Incidence rates were compared with prevalence data to identify their
      level of agreement. Spatial autocorrelation of the incidence rates was analyzed
      using Moran's Index, to check if spatial clustering occurs. Finally, the spatial
      relationship between schistosomiasis distribution and potential risk factors was
      assessed using multiple regression. RESULTS: Incidence rates for 2007-2008 were
      highly correlated with prevalence values (R2 = 0.79), indicating that in the case
      of Rwanda incidence data can be used as a proxy for prevalence data. We observed
      a focal distribution of schistosomiasis with a significant spatial
      autocorrelation (Moran's I > 0: 0,05-0.20 and p <= 0,05), indicating the
      occurrence of hotspots. Regarding risk factors, it was identified that the
      spatial pattern of schistosomiasis is significantly associated with wetland
      conditions and rice cultivation. CONCLUSION: In Rwanda the high density of health
      facilities and the standardized microscopic laboratory diagnostic allow the
      derived data to be used to complement prevalence studies to identify hotspots of
      schistosomiasis and its associated risk factors. This type of information, in
      turn, can support disease control interventions and monitoring.

PMID- 29070021
TI  - The relationship between multiple chronic diseases and depressive symptoms among
      middle-aged and elderly populations: results of a 2009 korean community health
      survey of 156,747 participants.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship between
      multiple chronic diseases and depressive symptoms in middle-aged and elderly
      populations. METHODS: This study was performed using the 2009 Korean Community
      Health Survey, which targeted adults over the age of 40 (N = 156,747
      participants, 88,749 aged 40-59 years and 67,998 aged >=60 years). The Korean
      version of the Center for Epidemiologic Studies Depression Scale (CES-D-K) was
      used as the measurement tool for depressive symptoms (CES-D-K score over 16).
      Multiple chronic diseases were defined as the concurrent presence of two or more
      chronic diseases. RESULTS: The prevalence and risk ratios (RRs) of experiencing
      depressive symptoms increased in the presence of multiple chronic diseases and
      with the number of comorbidities. The RRs of experiencing depressive symptoms
      according to the presence of multiple chronic diseases were higher in the middle
      aged population (adjusted RR, 1.939, 95% confidence limits (CL), 1.82-2.06) than
      in the elderly population (adjusted RR, 1.620, 95% CL, 1.55-1.69). In particular,
      middle-aged women who suffer from 4 or more chronic diseases have the highest RR
      (adjusted RR, 4.985, 95% CL, 4.13-6.03) for depressive symptoms. CONCLUSIONS:
      Multiple chronic diseases are closely associated with depressive symptoms in
      middle-aged and elderly populations. Given the mutual relationship between
      multiple chronic diseases and depressive symptoms, attention to and the
      assessment of depressive symptoms are needed in people with multiple chronic
      diseases.

PMID- 29070022
TI  - A method for allocating low-coverage sequencing resources by targeting haplotypes
      rather than individuals.
AB  - BACKGROUND: This paper describes a heuristic method for allocating low-coverage
      sequencing resources by targeting haplotypes rather than individuals. Low
      coverage sequencing assembles high-coverage sequence information for every
      individual by accumulating data from the genome segments that they share with
      many other individuals into consensus haplotypes. Deriving the consensus
      haplotypes accurately is critical for achieving a high phasing and imputation
      accuracy. In order to enable accurate phasing and imputation of sequence
      information for the whole population, we allocate the available sequencing
      resources among individuals with existing phased genomic data by targeting the
      sequencing coverage of their haplotypes. RESULTS: Our method, called AlphaSeqOpt,
      prioritizes haplotypes using a score function that is based on the frequency of
      the haplotypes in the sequencing set relative to the target coverage. AlphaSeqOpt
      has two steps: (1) selection of an initial set of individuals by iteratively
      choosing the individuals that have the maximum score conditional on the current
      set, and (2) refinement of the set through several rounds of exchanges of
      individuals. AlphaSeqOpt is very effective for distributing a fixed amount of
      sequencing resources evenly across haplotypes, which results in a reduction of
      the proportion of haplotypes that are sequenced below the target coverage.
      AlphaSeqOpt can provide a greater proportion of haplotypes sequenced at the
      target coverage by sequencing less individuals, as compared with other methods
      that use a score function based on haplotype frequencies in the population. A
      refinement of the initially selected set can provide a larger more diverse set
      with more unique individuals, which is beneficial in the context of low-coverage
      sequencing. We extend the method with an approach for filtering rare haplotypes
      based on their flanking haplotypes, so that only those that are likely to derive
      from a recombination event are targeted. CONCLUSIONS: We present a method for
      allocating sequencing resources so that a greater proportion of haplotypes are
      sequenced at a coverage that is sufficiently high for population-based imputation
      with low-coverage sequencing. The haplotype score function, the refinement step,
      and the new approach for filtering rare haplotypes make AlphaSeqOpt more
      effective for that purpose than previously reported methods for reducing
      sequencing redundancy.

PMID- 29070023
TI  - Portal vein thrombosis in liver cirrhosis: incidence, management, and outcome.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is a serious complication in liver
      cirrhosis with portal hypertension. We examined the treatment, recurrence and
      prognosis of PVT in cirrhotic patients. METHODS: The study subjects were all 90
      cirrhotic patients with PVT treated with danaparoid sodium (DS) at our department
      between July 2007 and September 2016. The mean age was 68 years and mean Child
      Pugh score was 7. All patients received 2500 U/day of DS for 2 weeks, and
      repeated in those who developed PVT recurrence after the initial therapy.
      RESULTS: Complete response was noted in 49% (n = 44), partial response (shrinkage
      >=70%) in 33% (n = 30), and no change (shrinkage <70%) in 18% (n = 16) of the
      patients after the initial course of treatment. DS treatment neither caused
      adverse events, particularly bleeding or thrombocytopenia, nor induced
      significant changes in serum albumin, total bilirubin, prothrombin time, and
      residual liver function. Re-treatment was required in 44 patients who showed PVT
      recurrence and 61% of these responded to the treatment. The cumulative recurrence
      rates at 1 and 2 posttreatment years were 26 and 30%, respectively. The
      recurrence rates were significantly lower in patients with acute type, compared
      to the chronic type (p = 0.0141). The cumulative survival rates at 1 and 3 years
      after treatment (including maintenance therapy with warfarin) were 83 and 60%,
      respectively, and were significantly higher in patients with acute type than
      chronic type (p = 0.0053). CONCLUSION: We can expect prognostic improvement of
      liver cirrhosis by warfarin following two-week DS therapy for the treatment of
      PVT in patients with liver cirrhosis safety and effectiveness. An early diagnosis
      of PVT along with the evaluation of the volume of PVT on CT and an early
      intervention would contribute to the higher efficacy of the treatment.

PMID- 29070025
TI  - Daylight photodynamic therapy versus cryosurgery for the treatment and
      prophylaxis of actinic keratoses of the face - protocol of a multicenter,
      prospective, randomized, controlled, two-armed study.
AB  - BACKGROUND: Photodynamic therapy with daylight (DL-PDT) is efficacious in
      treating actinic keratosis (AK), but the efficacy of field-directed, repetitive
      DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has
      not yet been investigated. METHODS/DESIGN: In this multicenter, prospective,
      randomized, controlled, two-armed, observer-blinded trial, patients with a
      minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly
      allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and
      cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire
      face are conducted over the course of 18 months. After preparation of the lesion
      and within 30 min after MAL application, patients expose themselves to daylight
      for 2 h. In the control group, lesion-directed cryosurgery is conducted at the
      first visit and, in the case of uncleared or new AK lesions, also at visits 2 to
      5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all
      existing and new AK lesions in the face. Cosmetic results and improvement of
      photoaging parameters are evaluated by means of a modified Dover scale. Primary
      outcome parameter is the cumulative number of AK lesions observed between visits
      2 and 6. Secondary outcome parameters are complete clearance of AK, new AK
      lesions since the previous visit, cosmetic results independently evaluated by
      both patient and physician, patient-reported pain (visual analogue scale),
      patient and physician satisfaction scores with cosmetic results, and patient
      reported quality of life (Dermatology Life Quality Index). Safety parameters are
      also documented (adverse events and serious adverse events). DISCUSSION: This
      clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and
      investigate possible rejuvenating effects of this treatment. (Trial registration:
      ClinicalTrials.gov Identifier: NCT02736760). TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014
      005121-13.

PMID- 29070026
TI  - A biomechanical comparison of Kirschner-wire fixation on fracture stability in
      Salter-Harris type I fractures of the proximal humeral physis in a porcine
      cadaveric model.
AB  - BACKGROUND: The physis is the weakest component of immature long bones, and
      physeal fractures constitute about 30% of fractures in growing dogs. Fractures of
      the proximal humeral physis typically have a Salter Harris type I or II
      configuration. These fractures require accurate reduction and adequate
      stabilization to allow for any potential continued longitudinal bone growth, in
      conjunction with physeal fracture healing. Conventional internal fixation of
      these fractures involves insertion of two parallel Kirschner wires, although
      other methods described include tension band wiring, Rush pinning, and lag
      screws. However these recommendations are based on anecdotal evidence, and
      information about the biomechanical stability of physeal fracture repair is
      sparse. The unique anatomical structure of the epiphyseal-metaphyseal complex
      makes the gripping of the epiphysis for ex vivo biomechanical testing of physeal
      fracture repair very challenging. The objective of our study was to
      biomechanically assess the optimal number (three, two or one) of implanted
      Kirschner wires in a porcine Salter Harris I proximal humeral physeal fracture
      model, using motion analysis tracking of peri-fragmental retro-reflective markers
      while constructs were subjected to a constant axial compression and a sinusoidal
      torque of +/- 2 Nm at 0.5 Hz for 250 cycles. RESULTS: There were significant
      differences between the three constructs (three, two or one Kirschner wire
      repair) for gross angular displacement (p < 0.001). The difference between three
      pins and two pins on toggle was not significant (p = 0.053), but both three-pin
      and two-pin fixation significantly reduced rotational toggle compared to one-pin
      fixation. Construct stiffness was not significantly different between any of the
      pin groups (p > 0.33). CONCLUSIONS: Motion analysis tracking using peri
      fragmental markers in this porcine model of physeal fracture repair found that
      the stability at the fracture site of one-pin fixation was significantly less
      than two-pin and three-pin fixation. Whether there was increased stabilization of
      these fractures with three-pin fixation compared to two-pin fixation was not
      conclusive in this porcine model.

PMID- 29070024
TI  - Plant hormone transporters: what we know and what we would like to know.
AB  - Hormone transporters are crucial for plant hormone action, which is underlined by
      severe developmental and physiological impacts caused by their loss-of-function
      mutations. Here, we summarize recent knowledge on the individual roles of plant
      hormone transporters in local and long-distance transport. Our inventory reveals
      that many hormones are transported by members of distinct transporter classes,
      with an apparent dominance of the ATP-binding cassette (ABC) family and of the
      Nitrate transport1/Peptide transporter family (NPF). The current need to explore
      further hormone transporter regulation, their functional interaction, transport
      directionalities, and substrate specificities is briefly reviewed.

PMID- 29070027
TI  - Absolute and relative reliability of acute effects of aerobic exercise on
      executive function in seniors.
AB  - BACKGROUND: Aging is accompanied by a decline of executive function. Aerobic
      exercise training induces moderate improvements of cognitive domains (i.e.,
      attention, processing, executive function, memory) in seniors. Most conclusive
      data are obtained from studies with dementia or cognitive impairment. Confident
      detection of exercise training effects requires adequate between-day reliability
      and low day-to-day variability obtained from acute studies, respectively. These
      absolute and relative reliability measures have not yet been examined for a
      single aerobic training session in seniors. METHODS: Twenty-two healthy and
      physically active seniors (age: 69 +/- 3 y, BMI: 24.8 +/- 2.2, VO2peak: 32 +/- 6
      mL/kg/bodyweight) were enrolled in this randomized controlled cross-over study. A
      repeated between-day comparison [i.e., day 1 (habituation) vs. day 2 & day 2 vs.
      day 3] of executive function testing (Eriksen-Flanker-Test, Stroop-Color-Test,
      Digit-Span, Five-Point-Test) before and after aerobic cycling exercise at 70% of
      the heart rate reserve [0.7 * (HRmax - HRrest)] was conducted. Reliability
      measures were calculated for pre, post and change scores. RESULTS: Large between
      day differences between day 1 and 2 were found for reaction times (Flanker- and
      Stroop Color testing) and completed figures (Five-Point test) at pre and post
      testing (0.002 < p < 0.05, 0.16 < np2 < 0.38). These differences notably declined
      when comparing day 2 and 3. Absolute between days variability (CoV) dropped from
      10 to 5% when comparing day 2 vs. day 3 instead of day 1 vs. day 2. Also ICC
      ranges increased from day 1 vs. day 2 (0.65 < ICC < 0.87) to day 2 vs. day 3
      (0.40 < ICC < 0.93). Interestingly, reliability measures for pre-post change
      scores were low (0.02 < ICC < 0.71). These data did not improve when comparing
      day 2 with day 3. During inhibition tests, reaction times showed excellent
      reliability values compared to the poor to fair reliability of accuracy.
      CONCLUSION: Notable habituation to the whole testing procedure should be
      considered as it increased the reliability of different executive function tests.
      Change scores of executive function after acute aerobic exercise cannot be
      detected reliably. Large intra- and inter-individual of responses to acute
      aerobic exercise in seniors can be presumed.

PMID- 29070028
TI  - riboviz: analysis and visualization of ribosome profiling datasets.
AB  - BACKGROUND: Using high-throughput sequencing to monitor translation in vivo,
      ribosome profiling can provide critical insights into the dynamics and regulation
      of protein synthesis in a cell. Since its introduction in 2009, this technique
      has played a key role in driving biological discovery, and yet it requires a
      rigorous computational toolkit for widespread adoption. DESCRIPTION: We have
      developed a database and a browser-based visualization tool, riboviz, that
      enables exploration and analysis of riboseq datasets. In implementation, riboviz
      consists of a comprehensive and flexible computational pipeline that allows the
      user to analyze private, unpublished datasets, along with a web application for
      comparison with published yeast datasets. Source code and detailed documentation
      are freely available from https://github.com/shahpr/RiboViz . The web-application
      is live at www.riboviz.org. CONCLUSIONS: riboviz provides a comprehensive
      database and analysis and visualization tool to enable comparative analyses of
      ribosome-profiling datasets. This toolkit will enable both the community of
      systems biologists who study genome-wide ribosome profiling data and also
      research groups focused on individual genes to identify patterns of
      transcriptional and translational regulation across different organisms and
      conditions.

PMID- 29070029
TI  - Skip metastasis in papillary thyroid carcinoma is difficult to predict in
      clinical practice.
AB  - BACKGROUND: Cervical lymph node metastases are very common in papillary thyroid
      cancer (PTC), and typically spread in a predictable stepwise fashion in clinical
      practice. However, lateral lymph node metastasis (LLNM) without central lymph
      node metastasis (CLNM) as skip metastasis is not rare in PTC. The aim of this
      study was to investigate the incidence, risk factors and pattern of skip
      metastasis in PTC. METHODS: A total of 271 patients with PTC and suspicious LLN
      diagnosed by pre-operation examinations who underwent total thyroidectomy and
      central lymph node dissection plus lateral lymph node dissection between January
      2008 and December 2011 were enrolled in this study. Clinicopathological features
      were collected, and the pattern of cervical lymph node metastasis and skip
      metastasis were analyzed. RESULTS: The LLNM rate was 74.9% (203/271, diagnosed by
      postoperative pathology examination) and significantly associated with
      extrathyroid extension (ETE), primary tumor located at the upper pole, and CLNM
      (p < 0.05). The skip metastasis rate was 14.8% (30/203) and was more frequently
      found in microcarcinoma patients, especially when the primary tumor size was
      <=0.5 cm (p = 0.001 OR = 12.9). However, skip metastasis was unrelated to the
      remaining factors examined. CONCLUSION: Small cancers with a pre-operation
      diagnosis of LLNM are more likely to have skip metastases, especially when the
      primary tumor size is less than 0.5 cm in diameter; however, this type of
      metastasis appears to develop in a random fashion. Thus, additional research is
      needed to identify potential predictive factors, such as a primary tumor located
      at the upper pole.

PMID- 29070030
TI  - Patient's and physician's awareness of kidney disease in coronary heart disease
      patients - a cross-sectional analysis of the German subset of the EUROASPIRE IV
      survey.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a common comorbid condition in
      coronary heart disease (CHD). CKD predisposes the patient to acute kidney injury
      (AKI) during hospitalization. Data on awareness of kidney dysfunction among CHD
      patients and their treating physicians are lacking. In the current cross
      sectional analysis of the German EUROASPIRE IV sample we aimed to investigate the
      physician's awareness of kidney disease of patients hospitalized for CHD and also
      the patient's awareness of CKD in a study visit following hospital discharge.
      METHODS: All serum creatinine (SCr) values measured during the hospital stay were
      used to describe impaired kidney function (eGFRCKD-EPI < 60 ml/min/1.73m2) at
      admission, discharge and episodes of AKI (KDIGO definition). Information
      extracted from hospital discharge letters and correct ICD coding for kidney
      disease was studied as a surrogate of physician's awareness of kidney disease.
      All patients were interrogated 0.5 to 3 years after hospital discharge, whether
      they had ever been told about kidney disease by a physician. RESULTS: Of the 536
      patients, 32% had evidence for acute or chronic kidney disease during the index
      hospital stay. Either condition was mentioned in the discharge letter in 22%, and
      72% were correctly coded according to ICD-10. At the study visit in the
      outpatient setting 35% had impaired kidney function. Of 158 patients with kidney
      disease, 54 (34%) were aware of CKD. Determinants of patient's awareness were
      severity of CKD (OReGFR 0.94; 95%CI 0.92-0.96), obesity (OR 1.97; 1.07-3.64),
      history of heart failure (OR 1.99; 1.00-3.97), and mentioning of kidney disease
      in the index event's hospital discharge letter (OR 5.51; 2.35-12.9). CONCLUSIONS:
      Although CKD is frequent in CHD, only one third of patients is aware of this
      condition. Patient's awareness was associated with kidney disease being mentioned
      in the hospital discharge letter. Future studies should examine how raising
      physician's awareness for kidney dysfunction may improve patient's awareness of
      CKD.

PMID- 29070031
TI  - 17q23.2q23.3 de novo duplication in association with speech and language
      disorder, learning difficulties, incoordination, motor skill impairment, and
      behavioral disturbances: a case report.
AB  - BACKGROUND: Chromosomal rearrangements involving 17q23 have been described
      rarely. Deletions at 17q23.1q23.2 have been reported in individuals with
      developmental delay and growth retardation, whereas duplications at 17q23.1q23.2
      appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes,
      located in 17q23.2, have been proposed to be responsible for the phenotypes
      observed in individuals with 17q23.1q23.2 deletions and duplications. In this
      report, we present the clinical phenotype of a child with a previously unreported
      de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region.
      CASE PRESENTATION: We report a 7.5-year-old boy with speech and language
      disorder, learning difficulties, incoordination, fine motor skill impairment,
      infrequent seizures with abnormal EEG, and behavior disturbances (mild self
      inflicted injuries, hyperactivity-inattention, and stereotyped hand movements).
      Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3.
      Both parents did not have the duplication indicating that this duplication is de
      novo in the child. CONCLUSIONS: The duplicated region encompasses 16 genes. It is
      possible that increased dosage of one or more genes in this region is responsible
      for the observed phenotype. The TANC2 gene is one of the genes in the duplicated
      region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat
      and coiled-coil containing) family which includes TANC1 and TANC2. These proteins
      are highly expressed in brain and play major roles in synapsis regulation. Hence,
      it is suggestive that TANC2 is the likely candidate gene responsible for the
      observed phenotype as an increased TANC2 dosage can potentially alter synapsis,
      resulting in neuronal dysfunction and the neurobehavioral phenotype observed in
      this child with 17q23.2q23.3 duplication.

PMID- 29070032
TI  - Collaborative partnership and the social value of clinical research: a
      qualitative secondary analysis.
AB  - BACKGROUND: Protecting human subjects from being exploited is one of the main
      ethical challenges for clinical research. However, there is also a responsibility
      to protect and respect the communities who are hosting the research. Recently,
      attention has focused on the most efficient way of carrying out clinical
      research, so that it benefits society by providing valuable research while
      simultaneously protecting and respecting the human subjects and the communities
      where the research is conducted. Collaboration between partners plays an
      important role and that is why we carried out a study to describe how
      collaborative partnership and social value are emerging in clinical research.
      METHODS: A supra-analysis design for qualitative descriptive secondary analysis
      was employed to consider a novel research question that pertained to nurse
      leaders' perceptions of ethical recruitment in clinical research and the ethics
      related aspects of clinical research from the perspective of administrative
      staff. The data consisted of two separate pre-existing datasets, comprising 451
      pages from 41 interviews, and we considered the research question by using
      deductive-inductive content analysis with NVivo software. A deductive analysis
      matrix was generated on the basis of two requirements, namely collaborative
      partnership and social value, as presented in An Ethical Framework for Biomedical
      Research by Emanuel et al. RESULTS: The findings showed that collaborative
      partnership was a cornerstone for ethical clinical research and ways to foster
      inter-partner collaboration were indicated, such as supporting mutual respect and
      equality, shared goals and clearly defined roles and responsibilities. In
      addition, the social value of clinical research was an important precondition for
      ethical clinical research and its realisation required the research partners to
      demonstrate collaboration and shared responsibility during the research process.
      However, concerns emerged that the multidimensional meaning of clinical research
      for society was not fully recognised. Achieving greater social value for clinical
      research required greater transparency, setting research priorities, shared
      responsibility for the dissemination and use of the findings and stronger
      community awareness of the ethics-related aspects of clinical research.
      CONCLUSIONS: Collaborative partnership and social values are essential for
      protecting the human subjects and communities involved in clinical research.

PMID- 29070033
TI  - Psychological distress, chronic conditions and quality of life in elderly
      hematologic cancer patients: study protocol of a prospective study.
AB  - BACKGROUND: Similar to most solid tumors, the incidence of hematologic
      malignancies has been rising. Although the median age at diagnosis is about 70
      years, little is known about psychosocial aspects and comorbid conditions in
      elderly patients with hematologic cancers. The main objectives of our study are
      to assess the prevalence of psychological distress, chronic conditions,
      functional disabilities, and quality of life in both elderly hematologic cancer
      patients aged >=70 years and an age-matched comparison sample of the general
      population. METHODS: We conduct a prospective study with three measuring points
      (t_1: >=5 years after first time hematologic cancer diagnosis / relapse; t_2 and
      t_3 six months and 1 year after t_1). In addition, we use a cross sectional study
      design to recruit a comparison sample of the general population matched by age
      and sex. Both samples, patients and the comparison group complete validated
      questionnaires measuring psychological distress, chronic conditions, functional
      disabilities, and quality of life as well as health care needs and health care
      utilization. DISCUSSION: Our study will provide both a data set offering detailed
      information about elderly hematologic cancer patients' physical, psychological
      and demographic characteristics, and reference data of the elderly general
      population. Furthermore, the study will provide important information for the
      development and implementation of psychooncological support offers and
      survivorship care plans.

PMID- 29070034
TI  - Diabetes and risk of cancer incidence: results from a population-based cohort
      study in northern Italy.
AB  - BACKGROUND: Aim of this study was to compare cancer incidence in populations with
      and without diabetes by cancer site. Furthermore, we aimed at comparing excess
      risk of cancer according to diabetes type, diabetes duration and treatment, the
      latter as regards Type 2 diabetes. METHODS: By use of the Reggio Emilia diabetes
      registry we classified the resident population aged 20-84 at December 31st 2009
      into two groups: with and without diabetes. By linking with the cancer registry
      we calculated the 2010-2013 cancer incidence in both groups. The incidence rate
      ratios (IRR) by cancer site, type of diabetes, diabetes duration, and as concerns
      Type 2 diabetes, by treatment regimen were computed using Poisson regression
      model and non-diabetic group as reference. RESULTS: The cohort included 383,799
      subjects without diabetes and 23,358 with diabetes. During follow-up, we
      identified 1464 cancer cases in subjects with diabetes and 9858 in the remaining
      population. Overall cancer incidence was higher in subjects with diabetes than in
      those without diabetes (IRR = 1.22, 95%CI 1.15-1.29), with similar results
      focusing on subjects with at least 2-year diabetes duration. Cancer sites driving
      overall increased risk were liver, pancreas, Colon rectum, and bladder in both
      sexes, corpus uteri for females. There was also suggestion of an increased risk
      for kidney cancer in females and a decreased risk for prostate cancer. Excess
      risk was found in patients with Type 2 diabetes, more marked among insulin users,
      especially with combined therapy. We observed an increasing risk for diabetes
      duration up to 10 years from diagnosis (IRR = 1.44, 95%CI 1.29-1.61) and a
      subsequent decrease to moderate-higher risk (IRR = 1.15, 95%CI 1.04-1.30).
      CONCLUSIONS: Our study indicates that the strength of association depends on
      specific cancer site. Insulin, monotherapy or combined therapy, per se or as an
      indication of poor blood glucose control, in addition to diabetes duration, may
      play a role in the association of diabetes and cancer.

PMID- 29070036
TI  - Comparing clinician descriptions of frailty and geriatric syndromes using
      electronic health records: a retrospective cohort study.
AB  - BACKGROUND: Geriatric syndromes, including frailty, are common in older adults
      and associated with adverse outcomes. We compared patients described in clinical
      notes as "frail" to other older adults with respect to geriatric syndrome burden
      and healthcare utilization. METHODS: We conducted a retrospective cohort study on
      18,341 Medicare Advantage enrollees aged 65+ (members of a large nonprofit
      medical group in Massachusetts), analyzing up to three years of administrative
      claims and structured and unstructured electronic health record (EHR) data. We
      determined the presence of ten geriatric syndromes (falls, malnutrition,
      dementia, severe urinary control issues, absence of fecal control, visual
      impairment, walking difficulty, pressure ulcers, lack of social support, and
      weight loss) from claims and EHR data, and the presence of frailty descriptions
      in clinical notes with a pattern-matching natural language processing (NLP)
      algorithm. RESULTS: Of the 18,341 patients, we found that 2202 (12%) were
      described as "frail" in clinical notes. "Frail" patients were older (82.3 +/- 6.8
      vs 75.9 +/- 5.9, p < .001) and had higher rates of healthcare utilization,
      including number of inpatient hospitalizations and emergency department visits,
      than the rest of the population (p < .001). "Frail" patients had on average 4.85
      +/- 1.72 of the ten geriatric syndromes studied, while non-frail patients had
      2.35 +/- 1.71 (p = .013). Falls, walking difficulty, malnutrition, weight loss,
      lack of social support and dementia were more highly correlated with frailty
      descriptions. The most common geriatric syndrome pattern among "frail" patients
      was a combination of walking difficulty, lack of social support, falls, and
      weight loss. CONCLUSIONS: Patients identified as "frail" by providers in clinical
      notes have higher rates of healthcare utilization and more geriatric syndromes
      than other patients. Certain geriatric syndromes were more highly correlated with
      descriptions of frailty than others.

PMID- 29070035
TI  - SaVanT: a web-based tool for the sample-level visualization of molecular
      signatures in gene expression profiles.
AB  - BACKGROUND: Molecular signatures are collections of genes characteristic of a
      particular cell type, tissue, disease, or perturbation. Signatures can also be
      used to interpret expression profiles generated from heterogeneous samples. Large
      collections of gene signatures have been previously developed and catalogued in
      the MSigDB database. In addition, several consortia and large-scale projects have
      systematically profiled broad collections of purified primary cells, molecular
      perturbations of cell types, and tissues from specific diseases, and the
      specificity and breadth of these datasets can be leveraged to create additional
      molecular signatures. However, to date there are few tools that allow the
      visualization of individual signatures across large numbers of expression
      profiles. Signature visualization of individual samples allows, for example, the
      identification of patient subcategories a priori on the basis of well-defined
      molecular signatures. RESULT: Here, we generate and compile 10,985 signatures
      (636 newly-generated and 10,349 previously available from MSigDB) and provide a
      web-based Signature Visualization Tool (SaVanT;
      http://newpathways.mcdb.ucla.edu/savant ), to visualize these signatures in user
      generated expression data. We show that using SaVanT, immune activation
      signatures can distinguish patients with different types of acute infections
      (influenza A and bacterial pneumonia). Furthermore, SaVanT is able to identify
      the prominent signatures within each patient group, and identify the primary cell
      types underlying different leukemias (acute myeloid and acute lymphoblastic) and
      skin disorders. CONCLUSIONS: The development of SaVanT facilitates large-scale
      analysis of gene expression profiles on a patient-level basis to identify patient
      subphenotypes, or potential therapeutic target pathways.

PMID- 29070037
TI  - Circulating matrix metalloproteinases are associated with arterial stiffness in
      patients with type 1 diabetes: pooled analysis of three cohort studies.
AB  - BACKGROUND: Altered regulation of extracellular matrix (ECM) composition by
      matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase
      (TIMPs) may contribute to arterial stiffening. We investigated associations
      between circulating MMP-1, -2, -3, -9, -10 and TIMP-1, and carotid-femoral pulse
      wave velocity (cfPWV) and pulse pressure (PP), as markers of arterial stiffness
      in type 1 diabetic patients. METHODS: Individuals with type 1 diabetes from three
      different cohorts were included in this study: EURODIAB Prospective Complications
      study (n = 509), LEACE (n = 370) and PROFIL (n = 638). Linear regression analyses
      were used to investigate cross-sectional associations between circulating levels
      of MMP-1, -2, -3, -9, -10, and TIMP-1 and cfPWV (n = 614) as well as office PP (n
      = 1517). Data on 24-h brachial and 24-h central PP were available in 638
      individuals from PROFIL. Analyses were adjusted for age, sex, duration of
      diabetes, HbA1c, mean arterial pressure (MAP), and eGFR, and additionally for
      other cardiovascular risk factors and presence of vascular complications.
      RESULTS: After adjustment for potential confounders and presence of vascular
      complications, circulating MMP-3 was associated with cfPWV [beta per 1 SD higher
      lnMMP3 0.29 m/s (0.02; 0.55)]. In addition, brachial and central 24-h PP
      measurements in PROFIL were significantly associated with MMP-2 [(1.40
      (0.47:2.33) and 1.43 (0.63:2.23)]. Pooled data analysis showed significant
      associations of circulating levels of MMP-1 and MMP-2 with office PP [beta per 1
      SD higher lnMMP-1 and lnMMP-2 = - 0.83 mmHg (95% CI - 1.50; - 0.16) and = 1.33
      mmHg (0.55; 2.10), respectively]. CONCLUSIONS: MMPs-1, -2, and -3 are
      independently associated with markers of arterial stiffening in patients with
      type 1 diabetes and may become therapeutic targets.

PMID- 29070038
TI  - Water extract of Rumex crispus prevents bone loss by inhibiting
      osteoclastogenesis and inducing osteoblast mineralization.
AB  - BACKGROUND: Rumex crispus root has traditionally been used in Asian medicine for
      the treatment of hemorrhage and dermatolosis. The aim of this study was to
      explore the pharmaceutical effects of water extract of Rumex crispus (WERC) on
      osteoblast and osteoclast differentiation. We also studied the effect of WERC on
      the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced
      trabecular bone destruction mice model. METHODS: High performance liquid
      chromatography analysis was used to identify three compounds (emodin,
      chrysophanol, and physcion) of WERC. The in vivo effect of WERC was examined
      using an administration of WERC or vehicle on the ICR mice with bone loss induced
      by intraperitoneal RANKL injection on day 0 and 1. All mice were sacrificed by
      cervical dislocation at day 7 and the femurs of mice were isolated for soft X-ray
      and Micro-CT analysis. The in vitro effect of WERC on osteoblast mineralization
      or osteoclast differentiation was examined by alizarin red S staining or by
      tartrate-resistant acid phosphatase staining and assay. To determine the
      transcription level of osteoblast or osteoclast-specific genes, real-time
      quantitative polymerase chain reaction was used. Western blot analysis was
      performed to study the effect of WERC on mitogen-activated protein kinases (MAPK)
      or nuclear factor-kappaB (NF-kappaB) signaling molecules. RESULTS: The presence
      of three compounds in WERC was determined. WERC significantly suppressed RANKL
      induced trabecular bone loss by preventing microstructural deterioration. In
      vitro, WERC increased osteoblast mineralization by enhancing the transcription of
      runt-related transcription factor 2 and its transcriptional coactivators, and by
      stimulating extracellular signal-regulated kinase phosphorylation. Furthermore,
      WERC significantly inhibited osteoclast differentiation by suppressing the
      activation of the RANKL signalings (MAPK and NF-kappaB) and the increasing
      inhibitory factors of nuclear factor of activated T cells cytoplasmic 1.
      CONCLUSION: This study showed that WERC could protect against osteoporosis and
      suggested that the possible mechanism of WERC might be related to increased
      osteoblast differentiation by activating Runx2 signaling and inhibition of
      osteoclast differentiation by suppression of RANKL signaling.

PMID- 29070039
TI  - Opportunities and challenges in the development of Cutaneotrichosporon
      oleaginosus ATCC 20509 as a new cell factory for custom tailored microbial oils.
AB  - Cutaneotrichosporon oleaginosus ATCC 20509, previously known as Trichosporon
      oleaginosus, Cryptococcus curvatus, Apiotrichum curvatum or Candida curvata D is
      an oleaginous yeast with several favorable qualities: it is fast growing,
      accumulates high amounts of lipid and has a very broad substrate spectrum. Its
      resistance to hydrolysis byproducts and genetic accessibility make it a promising
      cell factory for custom tailored microbial oils. However, literature about this
      organism is of varying degree of quality. Moreover, due to numerous changes of
      the species name, reports are highly scattered and poorly cited. This led to a
      poor integration of the findings into a unified body of knowledge. Particularly,
      errors in strain name usage and consequently citation are found even in most
      recent literature. To simplify future work, this review provides an overview of
      published studies and main findings regarding the metabolic capacities of C.
      oleaginosus.

PMID- 29070040
TI  - Care of the dialysis patient: Primary provider involvement and resource
      utilization patterns - a cohort study.
AB  - BACKGROUND: Efficient and safe delivery of care to dialysis patients is
      essential. Concerns have been raised regarding the ability of accountable care
      organizations to adequately serve this high-risk population. Little is known
      about primary care involvement in the care of dialysis patients. This study
      sought to describe the extent of primary care provider (PCP) involvement in the
      care of hemodialysis patients and the outcomes associated with that involvement.
      METHODS: In a retrospective cohort study, patients accessing a Midwestern
      dialysis network from 2001 to 2010 linked to United States Renal Database System
      and with >90 days follow up were identified (n = 2985). Outpatient visits were
      identified using Current Procedural Terminology (CPT)-4 codes, provider
      specialty, and grouped into quartiles-based on proportion of PCP visits per
      person-year (ppy). Top and bottom quartiles represented patients with high
      primary care (HPC) or low primary care (LPC), respectively. Patient
      characteristics and health care utilization were measured and compared across
      patient groups. RESULTS: Dialysis patients had an overall average of 4.5 PCP
      visits ppy, ranging from 0.6 in the LPC group to 6.9 in the HPC group. HPC
      patients were more likely female (43.4% vs. 35.3%), older (64.0 yrs. vs. 60.0
      yrs), and with more comorbidities (Charlson 7.0 vs 6.0). HPC patients had higher
      utilization (hospitalizations 2.2 vs. 1.8 ppy; emergency department visits 1.6 vs
      1.2 ppy) and worse survival (3.9 vs 4.3 yrs) and transplant rates (16.3 vs.
      31.5). CONCLUSIONS: PCPs are significantly involved in the care of hemodialysis
      patients. Patients with HPC are older, sicker, and utilize more resources than
      those managed primarily by nephrologists. After adjusting for confounders, there
      is no difference in outcomes between the groups. Further studies are needed to
      better understand whether there is causal impact of primary care involvement on
      patient survival.

PMID- 29070041
TI  - LncRNA RP11-436H11.5, functioning as a competitive endogenous RNA, upregulates
      BCL-W expression by sponging miR-335-5p and promotes proliferation and invasion
      in renal cell carcinoma.
AB  - BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs)
      play a crucial role in tumorigenesis. Here, we report a novel lncRNA, RP11
      436H11.5, that regulates renal cell carcinoma (RCC) cell proliferation and
      invasion by sponging miR-335-5p. METHODS: Expression of lncRNA RP11-436H11.5 was
      determined by a qRT-PCR assay in RCC tissues. RCC cell proliferation and invasion
      were measured by a cell proliferation assay and a transwell invasion assay.
      Expression of BCL-W was detected by a western blot assay. Interactions between
      lncRNA RP11-436H11.5 and miR-335-5p were measured by a luciferase reporter assay
      and a RNA-pull down assay. In vivo experiments were used to detect tumor
      formation. RESULTS: In this study, the qRT-PCR results illustrated that lncRNA
      RP11-436H11.5 was more highly expressed in RCC tissues than in adjacent normal
      renal tissues. The results of survival analysis indicated that patients in the
      high lncRNA RP11-436H11.5 group presented significantly worse outcomes compared
      with those in the low lncRNA RP11-436H11.5 group. Downregulation of lncRNA RP11
      436H11.5 suppressed RCC cell proliferation and invasion in vitro and in vivo.
      Luciferase reporter assay results demonstrated that lncRNA RP11-436H11.5 enhanced
      BCL-W expression by regulating miR-335-5p expression. LncRNA RP11-436H11.5 could
      function as a miR-335-5p decoy to derepress expression of BCL-W. CONCLUSIONS:
      LncRNA RP11-436H11.5 could function as a competing endogenous RNA to promote RCC
      cell proliferation and invasion, which might serve as a therapeutic application
      to suppress RCC progression.

PMID- 29070042
TI  - Effects of cow's milk beta-casein variants on symptoms of milk intolerance in
      Chinese adults: a multicentre, randomised controlled study.
AB  - BACKGROUND: A major protein component of cow's milk is beta-casein. The most
      frequent variants in dairy herds are A1 and A2. Recent studies showed that milk
      containing A1 beta-casein promoted intestinal inflammation and exacerbated
      gastrointestinal symptoms. However, the acute gastrointestinal effects of A1 beta
      casein have not been investigated. This study compared the gastrointestinal
      effects of milk containing A1 and A2 beta-casein versus A2 beta-casein alone in
      Chinese adults with self-reported lactose intolerance. METHODS: In this
      randomised, crossover, double-blind trial, with a 3-day dairy washout period at
      baseline, subjects were randomised to consume 300 mL of milk containing A1 and A2
      beta-casein (ratio 58:42; conventional milk) or A2 beta-casein alone; subjects
      consumed the alternative product after a 7-day washout period. Urine galactose
      was measured at baseline after a 15 g lactose load. Subjects completed 9-point
      visual analogue scales for gastrointestinal symptoms (borborygmus, flatulence,
      bloating, abdominal pain, stool frequency, and stool consistency) at baseline and
      at 1, 3, and 12 h after milk consumption. RESULTS: A total of 600 subjects were
      included. All six symptom scores at 1 and 3 h were significantly lower after
      consuming A2 beta-casein versus conventional milk (all P<0.0001). At 12 h,
      significant differences remained for bloating, abdominal pain, stool frequency,
      and stool consistency (all P<0.0001). Symptom scores were consistently lower with
      A2 beta-casein in both lactose absorbers (urinary galactose >=0.27 mmol/L) and
      lactose malabsorbers (urinary galactose <0.27 mmol/L). CONCLUSION: Milk
      containing A2 beta-casein attenuated acute gastrointestinal symptoms of milk
      intolerance, while conventional milk containing A1 beta-casein reduced lactase
      activity and increased gastrointestinal symptoms compared with milk containing A2
      beta-casein. Thus, milk-related gastrointestinal symptoms may result from the
      ingestion of A1 beta-casein rather than lactose in some individuals. TRIAL
      REGISTRATION: NCT02878876 , registered August 16, 2016. Retrospectively
      registered.

PMID- 29070043
TI  - The effect of renal denervation in an experimental model of chronic renal
      insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study).
AB  - BACKGROUND: Renal denervation (RDN) is a promising therapeutic method in
      cardiology. Its currently most investigated indication is resistant hypertension.
      Other potential indications are atrial fibrillation, type 2 diabetes mellitus and
      chronic renal insufficiency among others. Previous trials showed conflicting but
      promising results, but the real benefits of RDN are still under investigation.
      Patients with renal insufficiency and resistant hypertension are proposed to be a
      good target for this therapy due to excessive activation of renal sympathetic
      drive. However, only limited number of studies showed benefits for these
      patients. We hypothesize that in our experimental model of chronic kidney disease
      (CKD) due to ischemia with increased activity of the renin-angiotensin
      aldosterone system (RAAS), renal denervation can have protective effects by
      slowing or blocking the progression of renal injury. METHODS: An experimental
      biomodel of chronic renal insufficiency induced by ischemia was developed using
      selective renal artery embolization (remnant kidney porcine model). 27 biomodels
      were assessed. Renal denervation was performed in 19 biomodels (denervated
      group), and the remaining were used as controls (n = 8). The extent of renal
      injury and reparative process between the two groups were compared and assessed
      using biochemical parameters and histological findings. RESULTS: Viable remnant
      kidney biomodels were achieved and maintained in 27 swine. There were no
      significant differences in biochemical parameters between the two groups at
      baseline. Histological assessment proved successful RDN procedure in all
      biomodels in the denervated group. Over the 7-week period, there were significant
      increases in serum urea, creatinine, and aldosterone concentration in both
      groups. The difference in urea and creatinine levels were not statistically
      significant between the two groups. However, the level of aldosterone in the
      denervated was significantly lower in comparison to the controls. Histological
      assessment of renal arteries showed that RDN tends to produce more damage to the
      arterial wall in comparison to vessels in subjects that only underwent RAE. In
      addition, the morphological damage of kidneys, which was expressed as a ratio of
      damaged surface (or scar) to the overall surface of kidney, also did not show
      significant difference between groups. CONCLUSIONS: In this study, we were not
      able to show significant protective effect of RDN alone on ischemic renal
      parenchymal damage by either laboratory or histological assessments. However, the
      change in aldosterone level shows some effect of renal denervation on the RAAS
      system. We hypothesize that a combined blockade of the RAAS and the sympathetic
      system could provide more protective effects against acute ischemia. This has to
      be further investigated in future studies.

PMID- 29070044
TI  - Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and
      cyclophosphamide for ER-positive, HER2-negative breast cancer: study protocol for
      a randomized pilot trial.
AB  - BACKGROUND: The response to neoadjuvant chemotherapy (NAC) varies by estrogen
      receptor (ER) and human epidermal growth factor receptor 2 (HER2) statuses, with
      responses being lower in ER-positive, HER2-negative tumors as compared with ER
      negative, HER2-positive or triple-negative tumors. Neoadjuvant endocrine therapy
      (NET) is an attractive alternative to NAC for ER-positive, HER2-negative cancer.
      However, a prior trial comparing NET with standard NAC in ER-positive tumor
      showed that the difference of response was not significant. Studies demonstrated
      that the mTOR inhibitor everolimus could sensitize breast tumors to endocrine
      therapy. A pilot open-label, randomized trial has been designed to evaluate the
      feasibility, efficacy and tolerability of neoadjuvant everolimus plus letrozole
      versus NAC in treating postmenopausal women with ER-positive, HER2-negative
      breast cancer. METHODS: Forty postmenopausal women with non-metastatic ER
      positive, HER2-negative invasive breast cancer with a primary tumor > 2 cm or
      positive axillary lymph node(s) proved by biopsy will be randomly (1:1) enrolled
      from Sun Yat-Sen Memorial Hospital to receive neoadjuvant everolimus plus
      letrozole for 18 weeks or fluorouracil, epirubicin plus cyclophosphamide (FEC)
      for six cycles before surgery. Primary outcome is the feasibility of the trial.
      Secondary outcome measures include ultrasound response rate, pathological
      complete response rate, breast-conserving surgery rate, toxicities, and changes
      in the percentages of peripheral blood CD4+ T cells, CD8+ T cells, T helper
      cells, regulatory T cells, and NK cells. DISCUSSION: This is the first study to
      determine the feasibility, efficacy and tolerability of head-to-head neoadjuvant
      everolimus plus letrozole versus neoadjuvant FEC in treating postmenopausal women
      with ER-positive, HER2-negative breast cancer. The trial will provide evidence to
      assess the feasibility of a future multicenter, randomized controlled trial, and
      will provide valuable clinical data of the immunoregulatory effect of everolimus
      in breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov registry, ID:
      NCT02742051 . Registered on 7 April 2016.

PMID- 29070045
TI  - Haemoadsorption reduces the inflammatory response and improves blood flow during
      ex vivo renal perfusion in an experimental model.
AB  - BACKGROUND: Ex-vivo normothermic perfusion strategies are a promising new
      instrument in organ transplantation. The perfusion conditions are designed to be
      protective however the artificial environment can induce a local inflammatory
      response. The aim of this study was to determine the effect of incorporating a
      Cytosorb adsorber into an isolated kidney perfusion system. METHODS: Porcine
      kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex
      vivo reperfusion circuit. Pairs of kidneys were randomised to either control (n =
      5) or reperfusion with a Cytosorb adsorber (n = 5) integrated into the circuit.
      Tissue, blood and urine samples were taken for the measurement of inflammation
      and renal function. RESULTS: Baseline levels of cytokines (IL-6, TNFalpha, IL-8,
      IL-10, IL-1beta, IL-1alpha) were similar between groups. Levels of IL-6 and IL-8
      in the perfusate significantly increased during reperfusion in the control group
      but not in the Cytosorb group (P = 0.023, 0.049). Levels of the other cytokines
      were numerically lower in the Cytosorb group; however, this did not reach
      statistical significance. The mean renal blood flow (RBF) was significantly
      higher in the Cytosorb group (162 +/- 53 vs. 120 +/- 35 mL/min/100 g; P = 0.022).
      Perfusate levels of prostaglandin E2 were significantly lower in the Cytosorb
      group (642 +/- 762 vs. 3258 +/- 980 pg/mL; P = 0.0001). Levels of prostacyclin
      were significantly lower in the Cytosorb group at 1, 3 and 6 h of reperfusion (P
      = 0.008, 0.003, 0.0002). Levels of thromboxane were also significantly lower in
      the Cytosorb group throughout reperfusion (P = 0.005). Haemoadsorption had no
      effect on creatinine clearance (P = 0.109). CONCLUSION: Haemoadsorption can
      reduce the inflammatory response and improve renal blood flow during perfusion.
      Nonetheless, in this model haemoadsorption had no influence on renal function and
      this may relate to the broad-spectrum action of the Cytosorb adsorber that also
      removes potentially important anti-inflammatory mediators.

PMID- 29070046
TI  - Erratum to: Shock in the emergency department; a 12 year population based cohort
      study.

PMID- 29070047
TI  - On measuring and decomposing inequality of opportunity in access to health
      services among Tunisian children: a new approach for public policy.
AB  - BACKGROUND: The early years in children's life are the key to physical, cognitive
      language, and, socio-emotional skills development. So, it is of paramount
      importance in this period to be interested in different indicators that would
      influence the child's health. METHODS: This paper measures inequality of
      opportunities among Tunisian children concerning access to nutritional and
      healthy services using Human Opportunity-Index and Shapely decomposition methods.
      RESULTS: Many disparities between regions have been detected since 1982 until
      2012. Tunisian children face unequal opportunities to develop in terms of health,
      nutrition, cognitive, social, and emotional development. Likewise, we found that,
      parents' education, wealth, age of household head and geographic factors as key
      factors determining child development outcomes. CONCLUSION: Our findings
      suggested that childhood unequal opportunities in Tunisia are explained by
      pension funds deficiency and structural problem in the labor market. TRIAL
      REGISTRATION: The results of a health care intervention on human participants
      "retrospectively registered".

PMID- 29070048
TI  - A framework for the design, conduct and interpretation of randomised controlled
      trials in the presence of treatment changes.
AB  - BACKGROUND: When a randomised trial is subject to deviations from randomised
      treatment, analysis according to intention-to-treat does not estimate two
      important quantities: relative treatment efficacy and effectiveness in a setting
      different from that in the trial. Even in trials of a predominantly pragmatic
      nature, there may be numerous reasons to consider the extent, and impact on
      analysis, of such deviations from protocol. Simple methods such as per-protocol
      or as-treated analyses, which exclude or censor patients on the basis of their
      adherence, usually introduce selection and confounding biases. However, there
      exist appropriate causal estimation methods which seek to overcome these inherent
      biases, but these methods remain relatively unfamiliar and are rarely implemented
      in trials. METHODS: This paper demonstrates when it may be of interest to look
      beyond intention-to-treat analysis for answers to alternative causal research
      questions through illustrative case studies. We seek to guide trialists on how to
      handle treatment changes in the design, conduct and planning the analysis of a
      trial; these changes may be planned or unplanned, and may or may not be permitted
      in the protocol. We highlight issues that must be considered at the trial
      planning stage relating to: the definition of nonadherence and the causal
      research question of interest, trial design, data collection, monitoring,
      statistical analysis and sample size. RESULTS AND CONCLUSIONS: During trial
      planning, trialists should define their causal research questions of interest,
      anticipate the likely extent of treatment changes and use these to inform trial
      design, including the extent of data collection and data monitoring. A series of
      concise recommendations is presented to guide trialists when considering
      undertaking causal analyses.

PMID- 29070049
TI  - Analysis of the causes of failure after radical surgery in patients with PT3N0M0
      thoracic esophageal squamous cell carcinoma and consideration of postoperative
      radiotherapy.
AB  - BACKGROUND: Five-year overall survival rate of TESCC after surgery is low
      (approximately 30% to 60%), so it is meaningful to discuss the significance of
      PORT. METHODS: We retrospectively collected the data of 227 patients with PT3N0M0
      esophageal cancer (EC). The failure pattern after surgery was analyzed.
      Difference of adjuvant PORT in patients with PT3N0M0 TESCC and the appropriate
      population were explored based on the relevant studies. RESULTS: There were 58
      cases with intrathoracic locoregional recurrence (LRR) after radical surgery and
      27 cases with distant metastasis, including 10 cases of recurrence. The
      recurrence rate of mediastinal lymph nodes in the thoracic cavity was 50.0%.
      Univariate analysis revealed that compared with patients with middle and lower
      thoracic EC, the 3/5-year survival rate of patients with upper thoracic EC was
      significantly lower, accompanied with remarkably higher thoracic LRR. Compared
      with those with moderately- and well-differentiated TESCC, the 3/5-year survival
      rate of patients with poorly differentiated TESCC was significantly lower,
      whereas the distant metastasis rate was notably higher. Multivariate analysis
      revealed that different lesion locations and different pathologic differentiation
      were the independent prognostic factors. The lesion location and degree of
      differentiation were the independent influencing factors for thoracic LRR and
      distant metastasis, respectively. CONCLUSION: The intrathoracic LRR is the major
      failure pattern for patients with PT3N0M0 TESCC after conventional two-field
      lymphadenectomy. In addition, recurrence rate of PT3N0M0 TESCC was significantly
      higher in upper thoracic EC than in middle and lower thoracic EC. PORT is
      recommended to patients with PT3N0M0 upper TESCC.

PMID- 29070050
TI  - Potential barriers in healthcare access of the elderly population influenced by
      the economic crisis and the troika agreement: a qualitative case study in Lisbon,
      Portugal.
AB  - BACKGROUND: The recent economic and financial crisis in Portugal urged the
      Portuguese Government in April 2011 to request financial assistance from the
      troika austerity bail out program to get aid for its government debt. The troika
      agreement included health reforms and austerity measures of the National Health
      Service (NHS) in Portugal to save non-essential health care costs. This research
      aimed to identify potential barriers among the elderly population (aged 65 and
      above) to healthcare access influenced by the economic crisis and the troika
      agreement focussing on the Memorandum of Understanding on Specific Economic
      Policy Conditionality (MoU) in Lisbon metropolitan area, Portugal. METHODS: The
      qualitative study is including 13 semi-structured interviews of healthcare
      experts, municipality authority, health care providers, negotiator of the troika
      agreement, hospital managers, health economists and elderly. A content analysis
      was performed to evaluate the interviews applying Nvivo2011 software. The
      barriers identified were clustered towards the five areas of the 'Conceptual
      framework on health care access' by Levesque et al. (Int J Equity Health 12:18,
      2013). RESULTS: Healthcare access for the elderly was found inadequate in four
      areas of the framework: availability; appropriateness; approachability; and
      affordability. The fifth area on acceptability was not identified since the study
      neither followed a gender nor ethnic specific purpose. The main identified
      barriers were: current financial situation and pension cuts; insufficient
      provision and increased user fees in primary care; inadequate design and
      availability of hospital care service; lack of long-term care facilities;
      increased out-of-pocket-payment on pharmaceuticals; limitations in exemption
      allowances; cuts in non-emergent health transportation; increased waiting time
      for elective surgery; and poor unadapted housing conditions for elderly.
      CONCLUSIONS: The health reforms and health budget cuts in the MoU implemented as
      part of the troika agreement have been associated with increasing health
      inequalities in access to healthcare services for the elderly population. The
      majority of responses disclosed an increasing deficiency across the entire
      National Health Service (NHS) to collaborate, integrate and communicate between
      the different healthcare sectors for providing adequate care to the elderly. An
      urgent necessity of restructuring the health care system to adapt towards the
      elderly population was implied.

PMID- 29070052
TI  - Adherence to iron supplements among women receiving antenatal care at Mulago
      National Referral Hospital, Uganda-cross-sectional study.
AB  - BACKGROUND: Antenatal iron supplementation is a cost effective way of reducing
      iron deficiency anaemia among pregnant women in resource limited countries like
      Uganda. Poor adherence to iron supplements has limited its effectiveness in
      reducing maternal anaemia as evidenced by the high burden of iron deficiency
      anemia in Sub-saharan Africa. The aim of this study was to determine the level of
      and factors associated with adherence to iron supplementation among women
      attending antenatal clinic at Mulago National Referral Hospital, Kampala, Uganda.
      METHODS: Three hundred and seventy pregnant women were recruited in a cross
      sectional survey in Mulago National Referral Hospital antenatal clinic after
      informed consent between February and April 2014. Levels of adherence to iron
      supplements were assessed using visual analogue scale and factors associated
      collected using an interviewer administered questionnaire. RESULTS: About 12%
      (11.6%) of the mothers attending the antenatal clinic adhered to iron supplements
      over 30 day period. Mothers who had had four or more antenatal visits prior to
      the survey [odds ratio (OR) = 1.49, 95% confidence interval (CI) 1.12-1.97], had
      more than 2 week supply of iron supplements in the previous visit (OR 2.81, 95%
      CI 1.02-1.09), prior health education (OR 1.56, 95% CI 1.07-2.29) were more
      likely to adhere to iron supplements. Inadequate drug supplies and fear for side
      effects were the main reasons why participants missed the iron supplements.
      CONCLUSIONS: There was low adherence to iron supplements among mothers attending
      antenatal clinic at Mulago National Referral  Hospital. We recommend a national
      evaluation of adherence to iron supplements and look at ways of increasing
      adherence.

PMID- 29070051
TI  - Human antibodies against the myelin oligodendrocyte glycoprotein can cause
      complement-dependent demyelination.
AB  - BACKGROUND: Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are
      associated with a subset of inflammatory demyelinating diseases of the central
      nervous system such as acute disseminated encephalomyelitis and neuromyelitis
      optica spectrum disorders. However, whether human MOG antibodies are pathogenic
      or an epiphenomenon is still not completely clear. Although MOG is highly
      conserved within mammals, previous findings showed that not all human MOG
      antibodies bind to rodent MOG. We therefore hypothesized that human MOG antibody
      mediated pathology in animal models may only be evident using species-specific
      MOG antibodies. METHODS: We screened 80 human MOG antibody-positive samples for
      their reactivity to mouse and rat MOG using either a live cell-based assay or
      immunohistochemistry on murine, rat, and human brain tissue. Selected samples
      reactive to either human MOG or rodent MOG were subsequently tested for their
      ability to induce complement-mediated damage in murine organotypic brain slices
      or enhance demyelination in an experimental autoimmune encephalitis (EAE) model
      in Lewis rats. The MOG monoclonal antibody 8-18-C5 was used as a positive
      control. RESULTS: Overall, we found that only a subset of human MOG antibodies
      are reactive to mouse (48/80, 60%) or rat (14/80, 18%) MOG. Purified serum
      antibodies from 10 human MOG antibody-positive patients (8/10 reactive to mouse
      MOG, 6/10 reactive to rat MOG), 3 human MOG-negative patients, and 3 healthy
      controls were tested on murine organotypic brain slices. Purified IgG from one
      patient with high titers of anti-human, mouse, and rat MOG antibodies and robust
      binding to myelin tissue produced significant, complement-mediated myelin loss in
      organotypic brain slices, but not in the EAE model. Monoclonal 8-18-C5 MOG
      antibody caused complement-mediated demyelination in both the organotypic brain
      slice model and in EAE. CONCLUSION: This study shows that a subset of human MOG
      antibodies can induce complement-dependent pathogenic effects in a murine ex vivo
      animal model. Moreover, a high titer of species-specific MOG antibodies may be
      critical for demyelinating effects in mouse and rat animal models. Therefore,
      both the reactivity and titer of human MOG antibodies must be considered for
      future pathogenicity studies.

PMID- 29070055
TI  - A comparison of clinical efficacy between different surgical approaches for
      popliteal cyst.
AB  - BACKGROUND: A popliteal cyst is a benign swelling with synovial fluid located
      behind the knee joint. Popliteal cysts are often asymptomatic; however,
      symptomatic cysts may cause pain and may need surgery interventions. Here, we
      performed a perspective study to compare the clinical efficacy of different
      surgical approaches, including traditional open excision and advanced
      arthroscopic treatment. METHODS: A total of 76 patients with popliteal cysts were
      assigned into three groups by a randomized complete block design. Group A
      included 32 patients (15 males and 17 females, age 55.3 +/- 9.8 years) who
      received arthroscopic internal drainage of the cysts. Group B included 19
      patients (9 males and 10 females, age 55.4 +/- 7.6 years) who received open
      excision after arthroscopic treatment. Group C included 25 patients (11 males and
      14 females, age 54.2 +/- 8.5 years) who received open excision. All patients were
      followed up for an average of 13.7 +/- 2.4 months. The following parameters were
      compared: the time of surgery, during surgery, the length of incision, the
      incision healing rate, the visual analog scale (VAS) for pain, the
      hospitalization time, the rate of recovery to level 0-1 cysts, the recurrence
      rate, and the Lysholm score. RESULTS: Group A exhibited significant better
      outcomes compared to groups B and C in the length of incision (1.6 +/- 0.1 cm),
      the incision healing rate (100%), the postoperative VAS score (2.7 +/- 1.2), the
      hospitalization time (7.8 +/- 2.8 days), and the Lysholm score at the last follow
      up (85.8 +/- 5.2). The recurrence rate is significantly lower in groups A (3.1%)
      and B (5.2%) than group C (40%) (P < 0.001). CONCLUSIONS: Arthroscopic treatment
      for popliteal cysts exhibited better clinical outcomes with minimal invasion and
      can be recommended for future clinical interventions.

PMID- 29070053
TI  - Distribution of Blastocystis subtypes isolated from humans from an urban
      community in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Blastocystis is a cosmopolitan protist parasite found in the human
      gastrointestinal tract and is highly prevalent in developing countries. Recent
      molecular studies have revealed extensive genetic diversity, which has been
      classified into different subtypes (STs) based on sequence analysis of small
      subunit ribosomal RNA gene. Blastocystis is one of the most common fecal
      parasites in Brazil, but the diversity of subtypes remains unknown in the
      country. This study aimed to determine the distribution of Blastocystis STs in an
      urban community in Duque de Caxias, Rio de Janeiro, Brazil. METHODS: A total of
      64 stool samples positive for Blastocystis in Pavlova's medium were subtyped by
      PCR and sequenced using primers targeting the small subunit rRNA gene, in
      addition to phylogenetic analysis and subtype-specific PCR using sequence-tagged
      site (STS) primers. RESULTS: Endolimax nana (14%), Entamoeba complex (10.5%),
      Taenia sp. (0.6%), Trichuris trichiura (1.3%) and Enterobius vermicularis (1.3%)
      were detected in Blastocystis-positive samples. Of the 64 samples tested by
      PCR/DNA sequencing, 55 were identified as ST1 (42%), ST3 (49%), ST2 (7%) and ST4
      (2%), and the presence of mixed ST (ST1 + ST3) infection was detected in nine
      samples (14%). CONCLUSIONS: DNA sequencing and phylogenetic analysis of Brazilian
      Blastocystis isolates identified four different subtypes. To our knowledge, this
      study provided the first genetic characterization of Blastocystis subtypes in an
      urban area of Rio de Janeiro, Brazil. We also identified ST4 for the first time
      in Brazil. Further studies are necessary to determine the distribution of STs
      across human populations in Rio de Janeiro.

PMID- 29070054
TI  - Targeting the NLRP3 inflammasome to attenuate spinal cord injury in mice.
AB  - BACKGROUND: Spinal cord injury (SCI) is a devastating disease, which results in
      tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important
      role in the mechanism of diverse diseases. However, no studies have demonstrated
      the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors
      in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome
      activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert
      neuroprotective effects in a mouse model of SCI. METHODS: SCI was performed using
      an aneurysm clip with a closing force of 30 g at the level of the T6-T7 vertebra
      for 1 min. Motor recovery was evaluated by an open-field test. Neuronal death was
      assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and
      Nissl staining. Mitochondrial dysfunction was determined by quantitative real
      time polymerase chain reaction (qPCR), western blot, and detection of
      mitochondrial membrane potential level. Microglia/macrophage activation and
      astrocytic response were evaluated by immunofluorescence labeling. RESULTS:
      Inhibition of NLRP3 inflammasome activation by pharmacologic inhibitor BAY 11
      7082 or A438079 reduced neuronal death, attenuated spinal cord anatomic damage,
      and promoted motor recovery. Furthermore, BAY 11-7082 or A438079 directly
      attenuated the levels of NLRP3 inflammasome and proinflammatory cytokines.
      Moreover, BAY 11-7082 or A438079 alleviated microglia/macrophage activation,
      neutrophils infiltration, and reactive gliosis, as well as mitochondrial
      dysfunction. CONCLUSIONS: Collectively, our results demonstrate that
      pharmacologic suppression of NLRP3 inflammasome activation controls
      neuroinflammation, attenuates mitochondrial dysfunction, alleviates the severity
      of spinal cord damage, and improves neurological recovery after SCI. These data
      strongly indicate that the NLRP3 inflammasome is a vital contributor to the
      secondary damage of SCI in mice.

PMID- 29070056
TI  - Ecology of West Nile virus across four European countries: empirical modelling of
      the Culex pipiens abundance dynamics as a function of weather.
AB  - BACKGROUND: Culex pipiens is the major vector of West Nile virus in Europe, and
      is causing frequent outbreaks throughout the southern part of the continent.
      Proper empirical modelling of the population dynamics of this species can help in
      understanding West Nile virus epidemiology, optimizing vector surveillance and
      mosquito control efforts. But modelling results may differ from place to place.
      In this study we look at which type of models and weather variables can be
      consistently used across different locations. METHODS: Weekly mosquito trap
      collections from eight functional units located in France, Greece, Italy and
      Serbia for several years were combined. Additionally, rainfall, relative humidity
      and temperature were recorded. Correlations between lagged weather conditions and
      Cx. pipiens dynamics were analysed. Also seasonal autoregressive integrated
      moving-average (SARIMA) models were fitted to describe the temporal dynamics of
      Cx. pipiens and to check whether the weather variables could improve these
      models. RESULTS: Correlations were strongest between mean temperatures at short
      time lags, followed by relative humidity, most likely due to collinearity.
      Precipitation alone had weak correlations and inconsistent patterns across sites.
      SARIMA models could also make reasonable predictions, especially when longer time
      series of Cx. pipiens observations are available. CONCLUSIONS: Average
      temperature was a consistently good predictor across sites. When only short time
      series (~ < 4 years) of observations are available, average temperature can
      therefore be used to model Cx. pipiens dynamics. When longer time series (~ > 4
      years) are available, SARIMAs can provide better statistical descriptions of Cx.
      pipiens dynamics, without the need for further weather variables. This suggests
      that density dependence is also an important determinant of Cx. pipiens dynamics.

PMID- 29070057
TI  - Next-generation mapping: a novel approach for detection of pathogenic structural
      variants with a potential utility in clinical diagnosis.
AB  - BACKGROUND: Massively parallel DNA sequencing, such as exome sequencing, has
      become a routine clinical procedure to identify pathogenic variants responsible
      for a patient's phenotype. Exome sequencing has the capability of reliably
      identifying inherited and de novo single-nucleotide variants, small insertions,
      and deletions. However, due to the use of 100-300-bp fragment reads, this
      platform is not well powered to sensitively identify moderate to large structural
      variants (SV), such as insertions, deletions, inversions, and translocations.
      METHODS: To overcome these limitations, we used next-generation mapping (NGM) to
      image high molecular weight double-stranded DNA molecules (megabase size) with
      fluorescent tags in nanochannel arrays for de novo genome assembly. We
      investigated the capacity of this NGM platform to identify pathogenic SV in a
      series of patients diagnosed with Duchenne muscular dystrophy (DMD), due to large
      deletions, insertion, and inversion involving the DMD gene. RESULTS: We
      identified deletion, duplication, and inversion breakpoints within DMD. The sizes
      of deletions were in the range of 45-250 Kbp, whereas the one identified
      insertion was approximately 13 Kbp in size. This method refined the location of
      the break points within introns for cases with deletions compared to current
      polymerase chain reaction (PCR)-based clinical techniques. Heterozygous SV were
      detected in the known carrier mothers of the DMD patients, demonstrating the
      ability of the method to ascertain carrier status for large SV. The method was
      also able to identify a 5.1-Mbp inversion involving the DMD gene, previously
      identified by RNA sequencing. CONCLUSIONS: We showed the ability of NGM
      technology to detect pathogenic structural variants otherwise missed by PCR-based
      techniques or chromosomal microarrays. NGM is poised to become a new tool in the
      clinical genetic diagnostic strategy and research due to its ability to
      sensitively identify large genomic variations.

PMID- 29070058
TI  - Potential of Lanistes varicus in limiting the population of Bulinus truncatus.
AB  - OBJECTIVE: To determine the ability of the Ampullariid, Lanistes varicus to prey
      on egg masses and juveniles of Bulinus truncatus snails, an intermediate host of
      urogenital schistosomiasis in West Africa. RESULTS: Lanistes varicus was found to
      feed voraciously on egg masses and juveniles of Bulinus truncatus, consuming all
      egg masses (20 -25) exposed to it within 24 h. Also, 95-100% of 1-2 days old B.
      truncatus snails exposed to a single L. varicus snail was consumed within 4 days.
      The presence of L. varicus snails greatly increased mortality in B. truncatus
      with mortality increasing with increase in the number of L. varicus snails in the
      mixture of the two snail species. The current study has demonstrated under
      laboratory conditions that the Ghanaian strain of L. varicus has the potential of
      limiting the population of B. truncatus snails, and contribute to the control of
      urogenital schistosomiasis in West Africa.

PMID- 29070059
TI  - Synergistic effect of PB2 283M and 526R contributes to enhanced virulence of H5N8
      influenza viruses in mice.
AB  - Highly pathogenic avian influenza (HPAI) H5N8 virus has caused considerable
      economic losses to poultry industry and poses a great threat to public health.
      Our previous study revealed two genetically similar HPAI H5N8 viruses displaying
      completely different virulence in mice. However, the molecular basis for viral
      pathogenicity to mammals remains unknown. Herein, we generated a series of
      reassortants between the two viruses and evaluated their virulence in mice. We
      demonstrated that 283M in PB2 is a new mammalian virulence marker for H5 viruses
      and that synergistic effect of amino acid residues 283M and 526R in PB2 is
      responsible for high virulence of the HPAI H5N8 virus. Analysis of available PB2
      sequences showed that PB2 283M is highly conserved among influenza A viruses,
      while PB2 526R presents in most of human H3N2 and H5N1 isolates. Further study
      confirmed that the residues 283M and 526R had similar impacts on an HPAI H5N1
      virus, suggesting that influenza viruses with both residues may replicate well in
      mammalian hosts. Together, these results present new insights for synergistic
      effect of 283M and 526R in PB2 of H5 HPAI virus on virulence to mammalian host,
      furthering our understanding of the pathogenesis of influenza A virus.

PMID- 29070060
TI  - The relationship between childhood body weight and dental caries experience: an
      umbrella systematic review protocol.
AB  - BACKGROUND: Obesity and dental caries are global public health problems which can
      impact in childhood and throughout the life course. In simple terms, childhood
      dental caries and body weight are linked via the common risk factor of diet. An
      association between dental caries and obesity has been described in a number of
      studies and reviews. However, similarly, a relationship has also been noted
      between low body weight and caries experience in children. This protocol will
      provide the framework for an umbrella review to address the following question:
      Does the available evidence support a relationship between dental caries
      experience and body weight in the child population? METHODS: This review protocol
      outlines the process to carry out an umbrella systematic review which will
      synthesise previous reviews of childhood dental caries experience and body
      weight. An umbrella review methodology will be used to examine the methodological
      and reporting quality of existing reviews. DISCUSSION: The final umbrella review
      aims to aggregate the available evidence in order to provide a summary for
      policymakers and to inform healthcare interventions. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42016047304.

PMID- 29070061
TI  - Effectiveness of real-time polymerase chain reaction assay for the detection of
      Mycobacterium tuberculosis in pathological samples: a systematic review and meta
      analysis.
AB  - BACKGROUND: Rapid and accurate diagnosis of tuberculosis (TB) is key to manage
      the disease and to control and prevent its transmission. Many established
      diagnostic methods suffer from low sensitivity or delay of timely results and are
      inadequate for rapid detection of Mycobacterium tuberculosis (MTB) in pulmonary
      and extra-pulmonary clinical samples. This study examined whether a real-time
      polymerase chain reaction (RT-PCR) assay, with a turn-a-round time of 2 h, would
      prove effective for routine detection of MTB by clinical microbiology
      laboratories. METHODS: A systematic literature search was performed for
      publications in any language on the detection of MTB in pathological samples by
      RT-PCR assay. The following sources were used MEDLINE via PubMed, EMBASE, BIOSIS
      Citation Index, Web of Science, SCOPUS, ISI Web of Knowledge and Cochrane
      Infectious Diseases Group Specialised Register, grey literature, World Health
      Organization and Centres for Disease Control and Prevention websites. Forty-six
      studies met set inclusion criteria. Generated pooled summary estimates (95% CIs)
      were calculated for overall accuracy and bivariate meta-regression model was used
      for meta-analysis. RESULTS: Summary estimates for pulmonary TB (31 studies) were
      as follows: sensitivity 0.82 (95% CI 0.81-0.83), specificity 0.99 (95% CI 0.99
      0.99), positive likelihood ratio 43.00 (28.23-64.81), negative likelihood ratio
      0.16 (0.12-0.20), diagnostic odds ratio 324.26 (95% CI 189.08-556.09) and area
      under curve 0.99. Summary estimates for extra-pulmonary TB (25 studies) were as
      follows: sensitivity 0.70 (95% CI 0.67-0.72), specificity 0.99 (95% CI 0.99
      0.99), positive likelihood ratio 29.82 (17.86-49.78), negative likelihood ratio
      0.33 (0.26-0.42), diagnostic odds ratio 125.20 (95% CI 65.75-238.36) and area
      under curve 0.96. CONCLUSIONS: RT-PCR assay demonstrated a high degree of
      sensitivity for pulmonary TB and good sensitivity for extra-pulmonary TB. It
      indicated a high degree of specificity for ruling in TB infection from sampling
      regimes. This was acceptable, but may better as a rule out add-on diagnostic
      test. RT-PCR assays demonstrate both a high degree of sensitivity in pulmonary
      samples and rapidity of detection of TB which is an important factor in achieving
      effective global control and for patient management in terms of initiating early
      and appropriate anti-tubercular therapy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42015027534 .

PMID- 29070062
TI  - Microbial biodiversity assessment of the European Space Agency's ExoMars 2016
      mission.
AB  - BACKGROUND: The ExoMars 2016 mission, consisting of the Trace Gas Orbiter and the
      Schiaparelli lander, was launched on March 14 2016 from Baikonur, Kazakhstan and
      reached its destination in October 2016. The Schiaparelli lander was subject to
      strict requirements for microbial cleanliness according to the obligatory
      planetary protection policy. To reach the required cleanliness, the ExoMars 2016
      flight hardware was assembled in a newly built, biocontrolled cleanroom complex
      at Thales Alenia Space in Turin, Italy. In this study, we performed
      microbiological surveys of the cleanroom facilities and the spacecraft hardware
      before and during the assembly, integration and testing (AIT) activities.
      METHODS: Besides the European Space Agency (ESA) standard bioburden assay, that
      served as a proxy for the microbiological contamination in general, we performed
      various alternative cultivation assays and utilised molecular techniques,
      including quantitative PCR and next generation sequencing, to assess the absolute
      and relative abundance and broadest diversity of microorganisms and their
      signatures in the cleanroom and on the spacecraft hardware. RESULTS: Our results
      show that the bioburden, detected microbial contamination and microbial diversity
      decreased continuously after the cleanroom was decontaminated with more effective
      cleaning agents and during the ongoing AIT. The studied cleanrooms and change
      room were occupied by very distinct microbial communities: Overall, the change
      room harboured a higher number and diversity of microorganisms, including
      Propionibacterium, which was found to be significantly increased in the change
      room. In particular, the so called alternative cultivation assays proved
      important in detecting a broader cultivable diversity than covered by the
      standard bioburden assay and thus completed the picture on the cleanroom
      microbiota. CONCLUSION: During the whole project, the bioburden stayed at
      acceptable level and did not raise any concern for the ExoMars 2016 mission. The
      cleanroom complex at Thales Alenia Space in Turin is an excellent example of how
      efficient microbiological control is performed.

PMID- 29070063
TI  - Availability and performance of image/video-based vital signs monitoring methods:
      a systematic review protocol.
AB  - BACKGROUND: For many vital signs, monitoring methods require contact with the
      patient and/or are invasive in nature. There is increasing interest in developing
      still and video image-guided monitoring methods that are non-contact and non
      invasive. We will undertake a systematic review of still and video image-based
      monitoring methods. METHODS: We will perform searches in multiple databases which
      include MEDLINE, Embase, CINAHL, Cochrane library, IEEE Xplore and ACM Digital
      Library. We will use OpenGrey and Google searches to access unpublished or
      commercial data. We will not use language or publication date restrictions. The
      primary goal is to summarise current image-based vital signs monitoring methods,
      limited to heart rate, respiratory rate, oxygen saturations and blood pressure.
      Of particular interest will be the effectiveness of image-based methods compared
      to reference devices. Other outcomes of interest include the quality of the
      method comparison studies with respect to published reporting guidelines, any
      limitations of non-contact non-invasive technology and application in different
      populations. DISCUSSION: To the best of our knowledge, this is the first
      systematic review of image-based non-contact methods of vital signs monitoring.
      Synthesis of currently available technology will facilitate future research in
      this highly topical area. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      CRD42016029167.

PMID- 29070064
TI  - The effects of body weight loss and gain on arterial hypertension control: an
      observational prospective study.
AB  - BACKGROUND: Body weight changes are associated with significant variations in
      blood pressure (BP). Body mass modifications may, therefore, influence
      hypertension control in primary care. METHODS: Patients with a history of
      essential arterial hypertension were observed for 12 months. Anthropometric data
      and clinical BP were evaluated at the time of the recruitment and after 12 months
      of follow-up. The association between (body mass index) BMI change and BP control
      was analyzed by logistic regression. RESULTS: Sixteen thousand five hundred and
      sixty-four patients were recruited, while 13,631 patients (6336 men; 7295 women)
      finished the 1-year follow-up. In obese patients, a BMI decrease by at least 1
      kg/m2 was negatively associated with uncontrolled hypertension at the end of the
      follow-up (men p < 0.0001, OR = 0.586, 0.481-0.713, women p < 0.001, OR = 0.732,
      0.611-0.876). A similar association was observed in overweight patients (men p <
      0.05, OR = 0. 804, 95% CI: 0.636-0.997, women p < 0.05, OR = 0.730, 95% CI: 0.568
      0.937). A BMI increase of at least 1 kg/m2 was associated with a significantly
      higher odd of uncontrolled hypertension in obese (men p < 0.001, OR = 1.471,
      1.087-1.991, women p < 0.001, OR = 1.422, 1.104-1.833) and overweight patients
      (men p < 0.0001, OR = 1.901, 95% CI: 1.463-2.470, women p < 0.0001, OR = 1.647,
      95% CI: 1.304-2.080). CONCLUSIONS: Weight loss is inversely associated and weight
      increase is positively associated with the probability of uncontrolled
      hypertension in obese and overweight hypertensives.

PMID- 29070065
TI  - Salmonella Typhimurium, the major causative agent of foodborne illness
      inactivated by a phage lysis system provides effective protection against lethal
      challenge by induction of robust cell-mediated immune responses and activation of
      dendritic cells.
AB  - Salmonella Typhimurium infection via foodborne transmission remains a major
      public health threat even in developed countries. Vaccines have been developed to
      reduce the disease burden at the pre-harvest stage, but the cell-mediated immune
      response against intracellular invasion of the pathogen is not sufficiently
      elicited by conventional killed Salmonella vaccines, which are safer than live
      vaccines. In this study, we developed a genetically inactivated vaccine candidate
      by introducing lysis plasmid pJHL454 harboring the lambda phage holin-endolysin
      system into S. Typhimurium; we designated this vaccine JOL1950. In vitro
      expression of endolysin was validated by immunoblotting, and complete
      inactivation of JOL1950 cells was observed following 36 h of the lysis. Electron
      microscopic examinations by scanning electron microscopy and immunogold labeling
      transmission EM revealed conserved surface antigenic traits of the JOL1950 cells
      after lysis. An in vivo immunogenicity study in mice immunized with lysed cells
      showed significantly increased serum IgG, IgG1, and IgG2a levels. Further, we
      observed markedly increased in vitro cell proliferation and upregulation of Th1,
      Th2, and Th17 cytokines in the repulsed splenic T-cells of immunized mice. In
      dendritic cells (DCs) treated with lysed JOL1950, we observed a significant
      increase in dendritic cell activation, co-stimulatory molecule production, and
      levels of immunomodulatory cytokines. In addition, Th1 and Th17 cytokines were
      also released by naive CD4+ T-cells pulsed with primed DCs. Lysed JOL1950 also
      protected against lethal challenge in immunized mice. Together, these results
      indicate that our vaccine candidate has great potential to induce cell-mediated
      immunity against S. Typhimurium by facilitating the activation of DCs.

PMID- 29070066
TI  - The Edinburgh Consensus: preparing for the advent of disease-modifying therapies
      for Alzheimer's disease.
AB  - CONTEXT: This commentary discusses the implications of disease-modifying
      treatments for Alzheimer's disease which seem likely to appear in the next few
      years and results from a meeting of British experts in neurodegenerative diseases
      in Edinburgh. The availability of such treatments would help change public and
      professional attitudes and accelerate engagement with the prodromal and
      preclinical populations who might benefit from them. However, this would require
      an updated understanding of Alzheimer's disease, namely the important distinction
      between Alzheimer's disease and Alzheimer's dementia. CONSENSUS: Since treatments
      are likely to be most effective in the early stages, identification of clinically
      relevant brain changes (for example, amyloid burden using imaging or
      cerebrospinal fluid biomarkers) will be crucial. While current biomarkers could
      be useful in identifying eligibility for new therapies, trial data are not
      available to aid decisions about stopping or continuing treatment in clinical
      practice. Therefore, effective monitoring of safety and effectiveness when these
      treatments are introduced into clinical practice will be necessary to inform wide
      scale use. Equity of access is key but there is a tension between universal
      access for everyone with a diagnosis of Alzheimer's disease and specifying an
      eligible population most likely to respond. We propose the resources necessary
      for an optimal care pathway as well as the necessary education and training for
      primary and secondary care. CONCLUSION: The majority of current services in the
      UK and elsewhere would not be able to accommodate the specialist investigations
      required to select patients and prescribe these therapies. Therefore, a stepped
      approach would be necessary: from innovating sentinel clinical-academic centres
      that already have capacity to deliver the necessary phase IV trials, through
      early adoption in a hub and spoke model, to nationwide adoption for true equity
      of access. The optimism generated by recent and anticipated developments in the
      understanding and treatment of Alzheimer's disease presents a great opportunity
      to innovate and adapt our services to incorporate the next exciting development
      in the field of dementia.

PMID- 29070067
TI  - Prescription of potentially inappropriate medications among older people with
      intellectual disability: a register study.
AB  - BACKGROUND: Older people have a greater disease burden and are more likely than
      younger to be prescribed medications. They are also more sensitive to adverse
      effects. With this in mind, a range of medications have been suggested
      inappropriate in this population. People with intellectual disability (ID) have a
      higher disease burden than the general population, putting them at even greater
      risk of prescription of such medications. The aim of this study was to describe
      prescription of potentially inappropriate medications among older people with ID
      in relation to prescriptions among their age peers in the general population.
      METHODS: We established an administrative cohort of people with ID (ID cohort; n
      = 7936), using a Swedish national register. A referent cohort from the general
      population (gPop) was matched one-to-one by sex and year of birth. Data regarding
      prescription of potentially inappropriate medications were collected from the
      Swedish prescribed drug register for the years 2006-2012. RESULTS: People with ID
      were more likely than the general population to be prescribed medications with
      anticholinergic effects, intermediate- or long-acting benzodiazepines, and
      antipsychotics at least once during the study period, and also had more number of
      years with prescription. Except for benzodiazepines, those in the ID cohort with
      at least one prescription had larger amounts prescribed than those in the gPop
      cohort. People in the ID cohort were less likely than the general population to
      be prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Among those with at
      least one prescription of NSAIDs, those in the ID cohort had prescriptions during
      fewer years and in lower amounts than those in the gPop cohort. CONCLUSIONS:
      Although prescription of potentially inappropriate medications overall is more
      common among people with ID than in the general population, the opposite pattern
      is found for medications for pain management. This may be a result of pain being
      under-recognized and under-treated in this population. Thus, there is a need for
      training as well as increased knowledge and awareness among care and health care
      professionals regarding signs of adverse effects and the need of continuous
      evaluation of treatment in this vulnerable group.

PMID- 29070068
TI  - Common intensive care scoring systems do not outperform age and glasgow coma
      scale score in predicting mid-term mortality in patients with spontaneous
      intracerebral hemorrhage treated in the intensive care unit.
AB  - BACKGROUND: Intensive care scoring systems are widely used in intensive care
      units (ICU) around the world for case-mix adjustment in research and
      benchmarking. The aim of our study was to investigate the usefulness of common
      intensive care scoring systems in predicting mid-term mortality in patients with
      spontaneous intracerebral hemorrhage (ICH) treated in intensive care units (ICU).
      METHODS: We performed a retrospective observational study including adult
      patients with spontaneous ICH treated in Finnish ICUs during 2003-2012. We used
      six-month mortality as the primary outcome of interest. We used logistic
      regression to customize Acute Physiology and Chronic Health Evaluation (APACHE)
      II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure
      Assessment (SOFA) for six-month mortality prediction. To assess the usefulness of
      the scoring systems, we compared their discrimination and calibration with two
      simpler models consisting of age, Glasgow Coma Scale (GCS) score, and premorbid
      functional status. RESULTS: Totally 3218 patients were included. Overall six
      month mortality was 48%. APACHE II and SAPS II outperformed SOFA (area under the
      receiver operator curve [AUC] 0.83 and 0.84, respectively, vs. 0.73) but did not
      show any benefit over the simpler models in terms of discrimination (AUC 0.84, p
      > 0.05 for all models). SAPS II showed satisfactory calibration (p = 0.058 in the
      Hosmer-Lemeshow test), whereas all other models showed poor calibration (p <
      0.05). DISCUSSION: In this retrospective multi-center study, we found that SAPS
      II and APACHE II were of no additional prognostic value to a simple model based
      on only age and GCS score for patients with ICH treated in the ICU. In fact, the
      major predictive ability of APACHE II and SAPS II comes from their age and GCS
      score components. SOFA performed significantly poorer than the other models and
      is not applicable as a prognostic model for ICH patients. All models displayed
      poor calibration, highlighting the need for improved prognostic models for ICH
      patients. CONCLUSION: The common intensive care scoring systems did not
      outperform a simpler model based on only age and GCS score. Thus, the use of
      previous intensive care scoring systems is not warranted in ICH patients.

PMID- 29070069
TI  - Adenosine stress CMR T1-mapping detects early microvascular dysfunction in
      patients with type 2 diabetes mellitus without obstructive coronary artery
      disease.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with coronary
      microvascular dysfunction in the absence of obstructive coronary artery disease
      (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during
      adenosine stress can assess coronary vascular reactivity. We hypothesised that
      the non-contrast T1 response to vasodilator stress will be altered in patients
      with T2DM without CAD compared to controls due to coronary microvascular
      dysfunction. METHODS: Thirty-one patients with T2DM and sixteen matched healthy
      controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1
      mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE)
      imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all
      patients by coronary computed tomographic angiography. RESULTS: All subjects had
      normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial
      perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 +/- 0.44
      vs 2.01 +/- 0.42; p = 0.008). There was no difference in rest native T1 values (p
      = 0.59). During adenosine stress, T1 values increased significantly in both T2DM
      patients (from 1196 +/- 32 ms to 1244 +/- 44 ms, p < 0.001) and controls (from
      1194 +/- 26 ms to 1273 +/- 44 ms, p < 0.001). T2DM patients showed blunted
      relative stress non-contrast T1 response (T2DM: DeltaT1 = 4.1 +/- 2.9% vs.
      CONTROLS: DeltaT1 = 6.6 +/- 2.6%, p = 0.007) due to a blunted maximal T1 during
      adenosine stress (T2DM 1244 +/- 44 ms vs. controls 1273 +/- 44 ms, p = 0.045).
      CONCLUSIONS: Patients with well controlled T2DM, even in the absence of arterial
      hypertension and significant CAD, exhibit blunted maximal non-contrast T1
      response during adenosine vasodilatory stress, likely reflecting coronary
      microvascular dysfunction. Adenosine stress and rest T1 mapping can detect
      subclinical abnormalities of the coronary microvasculature, without the need for
      gadolinium contrast agents. CMR may identify early features of the diabetic heart
      phenotype and subclinical cardiac risk markers in patients with T2DM, providing
      an opportunity for early therapeutic intervention.

PMID- 29070070
TI  - Molecular investigation of Cryptosporidium and Giardia in pre- and post-weaned
      calves in Hubei Province, China.
AB  - BACKGROUND: The protistan pathogens Cryptosporidium and Giardia can cause
      significant intestinal diseases in animals and humans. Cattle, particularly
      calves, carrying these protists can be significant reservoirs for human
      infections and disease. However, little is known about the genetic make-up of
      Cryptosporidium and Giardia populations in cattle and other ruminants in some
      regions of China. RESULTS: In the present study, PCR-based tools were used to
      genetically characterise these protists in faecal samples from a total of 339 pre
      and post-weaned calves from four distinct locations in Hubei Province using
      markers in the large (LSU) or small (SSU) subunits of nuclear ribosomal RNA
      genes. Cryptosporidium andersoni, C. bovis, C. ryanae and Giardia duodenalis
      assemblage E were detected in 0.6%, 10.9%, 4.1% and 22.6% of calves,
      respectively. CONCLUSIONS: This study is the first to report the prevalence of
      Cryptosporidium and Giardia in pre- and post-weaned calves in Hubei Province, and
      encourages large-scale molecular studies of animals and humans, in an effort to
      better understand the epidemiology of these enteric pathogens in China.

PMID- 29070071
TI  - McEnhancer: predicting gene expression via semi-supervised assignment of
      enhancers to target genes.
AB  - Transcriptional enhancers regulate spatio-temporal gene expression. While genomic
      assays can identify putative enhancers en masse, assigning target genes is a
      complex challenge. We devised a machine learning approach, McEnhancer, which
      links target genes to putative enhancers via a semi-supervised learning algorithm
      that predicts gene expression patterns based on enriched sequence features.
      Predicted expression patterns were 73-98% accurate, predicted assignments showed
      strong Hi-C interaction enrichment, enhancer-associated histone modifications
      were evident, and known functional motifs were recovered. Our model provides a
      general framework to link globally identified enhancers to targets and
      contributes to deciphering the regulatory genome.

PMID- 29070072
TI  - Prevalence and determinants of burnout syndrome among physicians in Cameroon: a
      research proposal.
AB  - OBJECTIVES: Burnout syndrome is a common psychological state, that may affect
      human healthcare providers due to their prolonged exposure to job stressors.
      Burnout can hinder optimal healthcare delivery. Hence this study aims to
      determine the prevalence and correlates of burnout syndrome amongst physicians in
      Cameroon. Specifically: (1) to determine the prevalence of burnout syndrome
      amongst Cameroonian doctors. (2) To identify potential determinants of burnout
      among Cameroonian doctors. (3) To compare the prevalence and determinants of
      burnout among specialist physicians and general practitioners in Cameroon.
      RESULTS: This cross-sectional study will include a minimum of 335 doctors working
      in five regions of Cameroon. Consenting physicians will be consecutively
      recruited and data on sociodemographic and work characteristics will be collected
      via a printed self-administered questionnaire and burnout will be assessed using
      the Maslach Burnout Inventory. Data will be analysed using Epi Info version 7 and
      a p value < 0.05 will be considered significant. Multivariable logistic
      regression will be used to identify determinants of burnout syndrome. Physicians'
      mental health is largely neglected in developing countries like Cameroon. Data
      from this research will help inform practitioners on the magnitude of the problem
      and favour the development of policies that improve the mental health of care
      providers.

PMID- 29070073
TI  - The dose of HBV genome contained plasmid has a great impact on HBV persistence in
      hydrodynamic injection mouse model.
AB  - BACKGROUND: Hydrodynamic injection (HI) of hepatitis B virus (HBV) mouse model is
      an useful tool for HBV related research in vivo. However, only 40% of C57/BL6
      mice injected with 10 MUg HBV genome contained plasmid (pAAV-HBV1.2), serum HBsAg
      more than 6 months and none of the BALB/c mice injected with 10 MUg pAAV-HBV1.2
      plasmid DNA, serum HBsAg positive more than 4 weeks in the previous study.
      METHODS: In this study, C57/BL6 and BALB/c mice were hydrodynamic injected with
      different doses of pAAV-HBV1.2 plasmid DNA. HBV related serum markers were
      detected by ELISA. ALT levels in the serum were measured using full automated
      biochemistry analyzer. HBcAg positive cells in the liver were detected by
      immunohistochemical staining. The mRNA levels of IRF3, ISGs including ISG15, OAS,
      PKR and immune factors including IFNgamma, TNFalpha, TGFbeta, IL-6, IL-10, PDL1
      in liver of the mice were quantified by qRT-PCR. RESULTS: The results showed that
      the mice injected with 100 MUg high-concentration or 1 MUg low-concentration of
      pAAV-HBV1.2 plasmid DNA did not excert dominant influence on HBV persistence. In
      contrast, injection of 5 MUg intermediate-dose of pAAV-HBV1.2 plasmid DNA led to
      significant prolonged HBsAg expression and HBV persistence in both C57/BL6 (80%
      of the mice with HBsAg positive more than 6 months) and BALB/c (60% of the mice
      with HBsAg positive more than 3 months) mice. IFNgamma was significant up
      regulated in liver of the mice injected with 1 MUg or 100 MUg pAAV-HBV1.2 plasmid
      DNA. TNFalpha was up-regulated significantly in liver of the mice injected with
      100 MUg pAAV-HBV1.2 plasmid DNA. Moreover, PDL1 was significant up-regulated in
      liver of the mice injected with 5 MUg pAAV-HBV1.2 plasmid DNA. CONCLUSION: In
      this paper we demonstrated that, in the HBV HI mouse model, the concentration of
      injected pAAV-HBV1.2 plasmid DNA contributes to the diverse kinetics of HBsAg and
      HBeAg in the serum as well as HBcAg expression level in the liver, which then
      determined the HBV persisternce, while the antiviral factors IFNgamma, TNFalpha
      as well as immune negative regulatory factor PDL1 play important roles on HBV
      persistence.

PMID- 29070074
TI  - Integrated care reform in urban China: a qualitative study on design, supporting
      environment and implementation.
AB  - BACKGROUND: Initiatives on integrated care between hospitals and community health
      centers (CHCs) have been introduced to transform the current fragmented health
      care delivery system into an integrated system in China. Up to date no research
      has analyzed in-depth the experiences of these initiatives based on perspectives
      from various stakeholders. This study analyzed the integrated care pilot in
      Hangzhou City by investigating stakeholders' perspectives on its design features
      and supporting environment, their acceptability of this pilot, and further
      identifying the enabling and constraining factors that may influence the
      implementation of the integrated care reform. METHODS: The qualitative study was
      carried out based on in-depth interviews and focus group discussions with 50 key
      informants who were involved in the policy-making process and implementation.
      Relevant policy documents were also collected for analysis. RESULTS: The pilot in
      Hangzhou was established as a CHC-led delivery system based on cooperation
      agreement between CHCs and hospitals to deliver primary and specialty care
      together for patients with chronic diseases. An innovative learning-from-practice
      mentorship system between specialists and general practitioners was also
      introduced to solve the poor capacity of general practitioners. The design of the
      pilot, its governance and organizational structure and human resources were
      enabling factors, which facilitated the integrated care reform. However, the main
      constraining factors were a lack of an integrated payment mechanism from health
      insurance and a lack of tailored information system to ensure its sustainability.
      CONCLUSIONS: The integrated care pilot in Hangzhou enabled CHCs to play as gate
      keeper and care coordinator for the full continuum of services across the health
      care providers. The government put integrated care a priority, and constructed an
      efficient design, governance and organizational structure to enable its
      implementation. Health insurance should play a proactive role, and adopt a shared
      financial incentive system to support integrated care across providers in the
      future.

PMID- 29070076
TI  - Social and cultural complexities of anti-malarial drug circulation: an
      ethnographic investigation in three rural remote communes of Cambodia.
AB  - BACKGROUND: Anti-malarial medicine has a central role in malaria case management
      in Cambodia. It is, therefore, essential to study how anti-malarial drugs are
      distributed and consumed. This study aims to understand the socio-cultural
      complexity of anti-malarial drugs provision and usage practices. METHODS: Semi
      structured interviews and observation were conducted in Cambodia at the communal,
      provincial, and national levels from January 2014 to January 2015. Health
      ministers, non-governmental officers, anti-malarial medicines distributors,
      village malaria volunteers and malaria patients were interviewed. FINDINGS: The
      findings show that artemisinin-based combination therapy (ACT) flows into
      unregulated outlets, and was sold without any diagnostic tests. Affordable
      Medicines Facility for malaria scheme (AMFm) cannot drive ineffective anti
      malarial medicines out of the market because ACT is still more expensive due to
      price absortion by private and public providers. Malaria patients might not
      consume ACT because of patients' notions of 'Korp', and pharmaceutical and
      parasitic familiarity. The findings reflect that neither public nor private
      institutions have the capacity and resources to control the flow of ACT from
      going into the unlicensed sector. They do not have the ability to ensure that ACT
      is consumed after a positive rapid diagnostic test. CONCLUSIONS: With a weak
      regulation system and ailing public health infrastructure, pharmaceutical
      neoliberal mechanism like AMFm is not an effective means to eradicate any forms
      of malaria. Therefore, horizontal programmes, such as public health
      infrastructure improvement, and population participation must be implemented.
      Ethnical responsibilities of medical practitioners must be enforced and be
      included into the national curriculum. The awareness of drug resistance must be
      implemented at all levels.

PMID- 29070075
TI  - Marburg virus-like particles by co-expression of glycoprotein and matrix protein
      in insect cells induces immune responses in mice.
AB  - BACKGROUND: Marburg virus (MARV) causes severe haemorrhagic fever in humans and
      nonhuman primates and has a high mortality rate. However, effective drugs or
      licensed vaccines are not currently available to control the outbreak and spread
      of this disease. METHODS: In this study, we generated MARV virus-like particles
      (VLPs) by co-expressing the glycoprotein (GP) and matrix protein (VP40) using the
      baculovirus expression system. MARV VLPs and three adjuvants, Poria cocos
      polysaccharide (PCP-II), poly(I:C) and aluminium hydroxide, were evaluated after
      intramuscular vaccination in mice. RESULTS: Murine studies demonstrated that
      vaccination with the MARV VLPs induce neutralizing antibodies and cellar immune
      responses. MARV VLPs and the PCP-II adjuvant group resulted in high titres of
      MARV-specific antibodies, activated relatively higher numbers of B cells and T
      cells in peripheral blood mononuclear cells (PBMCs), and induced greater cytokine
      secretion from splenocytes than the other adjuvants. CONCLUSION: MARV VLPs with
      the PCP-II adjuvant may constitute an effective vaccination and PCP-II should be
      further investigated as a novel adjuvant.

PMID- 29070077
TI  - Linagliptin versus sitagliptin in patients with type 2 diabetes mellitus: a
      network meta-analysis of randomized clinical trials.
AB  - BACKGROUND: Diabetes is one of the most common chronic and costly diseases
      worldwide and type 2 diabetes is the most common type which accounts for about
      90% of cases with diabetes. New medication-therapy regimens such as those
      containing linagliptin alone or in combination with other medications (within the
      category of DDP-4 inhibitors) must be evaluated in terms of efficacy and compared
      with other currently used drugs and then enter the medication list of the
      country. Hence, this study aimed to compare the clinical efficacy of the two
      drugs, i.e. linagliptin and sitagliptin, in patients with type 2 diabetes.
      METHODS: A systematic review was conducted to identify all clinical trials
      published by 2015 which compared the two drugs in patients with type 2 diabetes.
      Using keywords such as "linagliptin", "type 2 diabetes mellitus", "sitagliptin"
      and related combinations, we searched databases including Scopus, PubMed, and Web
      of Science. The quality of the selected studies was evaluated using the Jadad
      score. Considering primary and secondary outcomes extracted from the reviewed
      studies, a network meta-analysis was used to conduct a systematic comparison
      between the two studied drugs. RESULTS: This network meta-analysis included 32
      studies (Linagliptin vs PLB: n = 8, Sitagliptin vs PLB: n = 13, Linagliptin + MET
      vs PLB + MET: n = 4, and Sitagliptin + MET vs PLB + MET: n = 7) and a total of
      13,747 patients. The results showed no significant difference between linagliptin
      and sitagliptin in terms of key efficacy and safety outcomes such as HbA1c
      changes from baseline, body weight change from baseline, percentage of patients
      achieving HbA1c <7, and percentage of patients experiencing hypoglycemic events
      (p > 0.05). The results showed that the efficacy of the two drug regimens was the
      same. CONCLUSIONS: Based on the results, there was no significant difference
      between the two drugs, i.e. linagliptin and sitagliptin, in terms of efficacy; in
      other words, the efficacy of the two drugs was the same. Therefore, the use of
      these two drugs depends on their availability and cost. Graphical abstract of the
      network meta-analysis performed to evaluate the alternatives under the study.

PMID- 29070078
TI  - Prevalence of prenatal exposure to substances of abuse: questionnaire versus
      biomarkers.
AB  - Alcohol and drugs of abuse consumption in young adults, including women of
      childbearing age, has experienced significant increase over the past two decades.
      The use of questionnaires as the only measure to investigate prenatal alcohol and
      drugs of abuse exposure underestimates the real prevalence of exposure and could
      mislead to wrong conclusions. Therefore, the aim of this article was to compare
      reported rates of prenatal alcohol and drugs of abuse consumption with biomarkers
      of exposure by a comprehensive review of the available literature. We searched
      MEDLINE and EMBASE databases for articles catalogued between 1992 and 2015. We
      identified relevant published studies that assessed the comparison between
      prenatal exposure to alcohol and drugs of abuse assessed by self-reported
      questionnaire of consumption versus biomarkers of exposure. Thirteen studies were
      included regarding alcohol consumption, and seven of them about drugs of abuse.
      Women who admitted consumption during pregnancy by questionnaire varied from 0 to
      37% for alcohol, from 0 to 4.3% for cocaine, and 2.9% for tetrahydrocannabinol
      (THC). Positive biomarkers results ranged from 16 to 44% for alcohol, 15.4% for
      cocaine, and from 4 to 12.4% for THC. Biomarkers should always complement
      questionnaires, as it has been shown that self-report may underestimate prenatal
      exposure to substances of abuse.

PMID- 29070079
TI  - Implementation strategies to increase access and demand of long-lasting
      insecticidal nets: a before-and-after study and scale-up process in Mozambique.
AB  - BACKGROUND: The universal coverage bed nets campaign is a proven health
      intervention promoting increased access, ownership, and use of bed nets to reduce
      malaria burden. This article describes the intervention and implementation
      strategies that Mozambique carried out recently in order to improve access and
      increase demand for long-lasting insecticidal nets (LLINs). METHODS: A before-and
      after study with a control group was used during Stage I of the implementation
      process. The following strategies were tested in Stage I: (1) use of coupons
      during household registration; (2) use of stickers to identify the registered
      households; (3) new LLIN ascription formula (one LLIN for every two people). In
      Stage II, the following additional strategies were implemented: (4) mapping and
      micro-planning; (5) training; and (6) supervision. Odds ratio (OR) and 95%
      confidence interval (CI) were used to compare and establish differences between
      intervened and control districts in Stage I. Main outcomes were: percentage of
      LLINs distributed, percentage of target households benefited. RESULTS: In Stage
      I, 87.8% (302,648) of planned LLINs were distributed in the intervention
      districts compared to 77.1% (219,613) in the control districts [OR: 2.14 (95% CI
      2.11-2.16)]. Stage I results also showed that 80.6% (110,453) of households
      received at least one LLIN in the intervention districts compared to 72.8%
      (87,636) in the control districts [OR: 1.56 (95% CI 1.53-1.59)]. In Stage II,
      98.4% (3,536,839) of the allocated LLINs were delivered, covering 98.6%
      (1,353,827) of the registered households. CONCLUSIONS: Stage I results achieved
      better LLINs and household coverage in districts with the newly implemented
      strategies. The results of stage II were also encouraging. Additional strategies
      adaptation is required for a wide-country LLIN campaign.

PMID- 29070080
TI  - The influence of stage at diagnosis and molecular subtype on breast cancer
      patient survival: a hospital-based multi-center study.
AB  - BACKGROUND: Stage at diagnosis and molecular subtype are important clinical
      factors associated with breast cancer patient survival. However, subgroup
      survival data from a large study sample are limited in China. To estimate the
      survival differences among patients with different stages and various subtypes of
      breast cancer, we conducted a hospital-based multi-center study on breast cancer
      in Beijing, China. METHODS: All resident patients diagnosed with primary,
      invasive breast cancer between January 1, 2006 and December 31, 2010 from four
      selected hospitals in Beijing were included and followed up until December 31,
      2015. Hospital-based data of stage at diagnosis, hormone receptor status, and
      selected clinical characteristics, including body mass index (BMI), menopausal
      status, histological grade, and histological type, were collected from the
      medical records of the study subjects. Overall survival (OS) and cancer-specific
      survival (CSS) were estimated. Cox proportional hazards models were employed to
      evaluate the associations of stage at diagnosis and molecular subtype with
      patient survival. RESULTS: The 5-year OS and CSS rates for all patients were
      89.4% and 90.3%. Survival varied by stage and molecular subtype. The 5-year OS
      rates for patients with stage I, II, III, and IV diseases were 96.5%, 91.6%,
      74.8%, and 40.7%, respectively, and the corresponding estimates of 5-year CSS
      rates were 97.1%, 92.6%, 75.6%, and 42.7%, respectively. The 5-year OS rates for
      patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast
      cancer were 92.6%, 88.4%, 83.6%, and 82.9%, respectively, and the corresponding
      estimates of 5-year CSS rates were 93.2%, 89.1%, 85.4%, and 83.5%, respectively.
      Multivariate analysis showed that stage at diagnosis and molecular subtype were
      important prognostic factors for breast cancer. CONCLUSIONS: Survival of breast
      cancer patients varied significantly by stage and molecular subtype. Cancer
      screening is encouraged for the early detection and early diagnosis of breast
      cancer. More advanced therapies and health care policies are needed on HER2 and
      triple-negative subtypes.

PMID- 29070081
TI  - Understanding the experience of initiating community-based physical activity and
      social support by people with serious mental illness: a systematic review using a
      meta-ethnographic approach.
AB  - BACKGROUND: People with long-term serious mental illness live with severe and
      debilitating symptoms that can negatively influence their health and quality of
      life, leading to outcomes such as premature mortality, morbidity and obesity. An
      interplay of social, behavioural, biological and psychological factors is likely
      to contribute to their poor physical health. Participating in regular physical
      activity could bring symptomatic improvements, weight loss benefits, enhanced
      wellbeing and when undertaken in a community-based group setting can yield
      additional, important social support benefits. Yet poor uptake of physical
      activity by people with serious mental illness is a problem. This review will
      systematically search, appraise and synthesise the existing evidence that has
      explored the experience of community-based physical activity initiation and key
      features of social support within these contexts by adults with schizophrenia,
      bipolar affective disorder, major depressive disorder or psychosis using the meta
      ethnography approach. This new understanding may be key in designing more
      acceptable and effective community-based group PA programmes that meet patients'
      need and expectations. METHODS: This will be a systematic review of qualitative
      studies using the meta-ethnography approach. The following databases will be
      searched: ASSIA, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE,
      Health Technology Assessment Database, MEDLINE, PsycINFO, Sociological Abstracts,
      SPORTDiscus and Web of Science. Grey literature will also be sought. Eligible
      studies will use qualitative methodology; involve adults (>=18 years) with
      schizophrenia, bipolar affective disorder, major depressive disorder or
      psychosis; will report community-based group physical activity; and capture the
      experience of physical activity initiation and key features of social support
      from the perspective of the participant. Study selection and assessment of
      quality will be performed by two reviewers. Data will be extracted by one
      reviewer, tabled, and checked for accuracy by the second reviewer. The meta
      ethnography approach by Noblit and Hare (Meta-ethnography: synthesizing
      qualitative studies 11, 1988) will be used to synthesise the data. DISCUSSION:
      This systematic review is expected to provide new insights into the experience of
      community-based group physical activity initiation for adults who have a serious
      mental illness to inform person-centred improvements to the management of serious
      mental illness through physical activity. SYSTEMATIC REVIEW REGISTRATION: The
      protocol has been registered on the International Prospective Register of
      Systematic Reviews (PROSPERO) on 22/03/2017; (registration number CRD42017059948
      ).

PMID- 29070083
TI  - Human immunodeficiency virus infection acquired through a traditional healer's
      ritual: a case report.
AB  - BACKGROUND: Globally, over 36 million people were infected with human
      immunodeficiency virus by the end of 2015. The Sub-Saharan African region home to
      less than one-fifth of the global population disproportionately harbors over two
      thirds of the total infections and related deaths. Residents of Sub-Saharan
      Africa continue to face limited access to allopathic medicine and it is estimated
      that over 80% of primary health care needs in the region are met through
      traditional healing practices. It is known that some of these practices are
      performed in groups and the use of unsterilized instruments is common thus
      potentiating the transmission of human immunodeficiency virus. CASE PRESENTATION:
      A 29-year-old business woman of African origin residing in rural Tanzania
      presented at a screening event to confirm her human immunodeficiency virus
      status. Her past medical history was unremarkable and so were two past
      pregnancies. As per the antenatal clinic card for the second pregnancy, her human
      immunodeficiency virus serostatus was negative. She reported that she had been
      taken to a traditional healer to take an oath of remaining faithful during her
      husband's absence. The oath involved cutting of the healer's skin followed by
      hers using the same instrument. Approximately 4 months following this traditional
      ritual she developed a febrile illness accompanied by enlarged lymph nodes of her
      neck. She was investigated for malaria, typhoid fever, and urinary tract
      infection which were negative but she tested positive for human immunodeficiency
      virus. Owing to her disbelief regarding the human immunodeficiency virus status,
      she went to three other care and treatment clinics and the results remained
      similar. She denied any history of transfusion or extramarital affairs. She
      tested positive at the screening event and enzyme-linked immunosorbent assay for
      human immunodeficiency virus performed at our institution was reactive.
      Tenofovir, lamivudine, and efavirenz antiretroviral combination was initiated.
      CONCLUSIONS: Persistence of cultural norms involving exposure of bodily fluids
      and use of unsterilized instruments especially in the developing world remains a
      viable source of human immunodeficiency virus transmission especially in rural
      areas.

PMID- 29070082
TI  - Sex influences eQTL effects of SLE and Sjogren's syndrome-associated genetic
      polymorphisms.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) and primary Sjogren's syndrome
      (pSS) are autoimmune disorders characterized by autoantibodies, dysregulated B
      cells, and notably high female-to-male incidence ratios. Genome-wide association
      studies have identified several susceptibility SNPs for both diseases. Many SNPs
      in the genome are expression quantitative trait loci (eQTLs), with context
      dependent effects. Assuming that sex is a biological context, we investigated
      whether SLE/pSS SNPs act as eQTLs in B cells and used a disease-targeted approach
      to understand if they display sex-specific effects. METHODS: We used genome-wide
      genotype and gene expression data from primary B cells from 125 males and 162
      females. The MatrixEQTL R package was used to identify eQTLs within a genomic
      window of 2 Mb centered on each of 22 established SLE and/or pSS susceptibility
      SNPs. To find sex-specific eQTLs, we used a linear model with a SNP * sex
      interaction term. RESULTS: We found ten SNPs affecting the expression of 16
      different genes (FDR < 0.05). rs7574865-INPP1, rs7574865-MYO1B, rs4938573-CD3D,
      rs11755393-SNRPC, and rs4963128-PHRF1 were novel observations for the immune
      compartment and B cells. By analyzing the SNP * sex interaction terms, we
      identified six genes with differentially regulated expression in females compared
      to males, depending on the genotype of SLE/pSS-associated SNPs: SLC39A8 (BANK1
      locus), CD74 (TNIP1 locus), PXK, CTSB (BLK/FAM167A locus), ARCN1 (CXCR5 locus),
      and DHX9 (NCF2 locus). CONCLUSIONS: We identified several unknown sex-specific
      eQTL effects of SLE/pSS-associated genetic polymorphisms and provide novel
      insight into how gene-sex interactions may contribute to the sex bias in systemic
      autoimmune diseases.

PMID- 29070084
TI  - Productive, economic and risk assessment of grazing dairy systems with
      supplemented cows milked once a day.
AB  - Milking cows once a day (OAD) is a herd management practice that may help to
      reduce working effort and labour demand in dairy farms. However, a decrease in
      milk yield per cow occurs in OAD systems compared with twice a day (TAD) systems
      and this may affect profitability of dairy systems. The objective of this study
      was to assess productive and economic impact and risk of reducing milking
      frequency from TAD to OAD for grazing dairy systems, using a whole-farm model.
      Five scenarios were evaluated by deterministic and stochastic simulations: one
      scenario under TAD milking (TADAR) and four scenarios under OAD milking. The OAD
      scenarios assumed that milk yield per cow decreased by 30% (OAD30), 24% (OAD24),
      19% (OAD19) and 10% (OAD10), compared with TADAR scenario, based on experimental
      and commercial farms data. Stocking rate (SR) was increased in all OAD scenarios
      compared to TADAR and two levels of reduction in labour cost were tested, namely
      15% and 30%. Milk and concentrate feeds prices, and pasture and crop yields, were
      allowed to behave stochastically to account for market and climate variations,
      respectively, to perform risk analyses. Scenario OAD10 showed similar milk yield
      per ha compared with TADAR, as the increased SR compensated for the reduction in
      milk yield per cow. For scenarios OAD30, OAD24 and OAD19 the greater number of
      cows per ha partially compensated for the reduction of milk yield per cow and
      milk yield per ha decreased 21%, 15% and 10%, respectively, compared with TADAR.
      Farm operating profit per ha per year also decreased in all OAD scenarios
      compared with TADAR, and were US$684, US$161, US$ 303, US$424 and US$598 for
      TADAR, OAD30, OAD24, OAD19, OAD10, respectively, when labour cost was reduced 15%
      in OAD scenarios. When labour cost was reduced 30% in OAD scenarios, only OAD10
      showed higher profit (US$706) than TADAR. Stochastic simulations showed that
      exposure to risk would be higher in OAD scenarios compared with TADAR. Results
      showed that OAD milking systems might be an attractive alternative for farmers
      who can either afford a reduction in profit to gain better and more flexible
      working conditions or can minimise milk yield loss and greatly reduce labour
      cost.

PMID- 29070085
TI  - The South Dakota Model: Health Care Professions Student Disaster Preparedness and
      Deployment Training.
AB  - OBJECTIVE: The Association of American Medical Colleges recommended an increase
      in medical education for public health emergencies, bioterrorism, and weapons of
      mass destruction in 2003. The University of South Dakota Sanford School of
      Medicine (USD SSOM) implemented a 1-day training event to provide disaster
      preparedness training and deployment organization for health professions students
      called Disaster Training Day (DTD). METHODS: Hospital staff and emergency medical
      services personnel provided the lecture portion of DTD using Core Disaster Life
      Support (CDLS; National Disaster Life Support Foundation) as the framework. Pre
      test and post-test analyses were presented to the students. Small group
      activities covered leadership, anaphylaxis, mass fatality, points of dispensing
      deployment training, psychological first aid, triage, and personal protective
      equipment. Students were given the option to sign up for statewide deployment
      through the South Dakota Statewide Emergency Registry of Volunteers (SERV SD).
      DTD data and student satisfaction surveys from 2009 to 2016 were reviewed.
      RESULTS: Since 2004, DTD has provided disaster preparedness training to 2246
      students across 13 health professions. Significant improvement was shown on CDLS
      post-test performance with a t-score of -14.24 and a resulting P value of
      <0.00001. Students showed high levels of satisfaction on a 5-level Likert scale
      with overall training, small group sessions, and perceived self-competency
      relating to disaster response. SERV SD registration increased in 2015, and 77.5%
      of the participants registered in 2016. CONCLUSION: DTD at the USD SSOM provides
      for an effective 1-day disaster training course for health professions students.
      Resources from around the state were coordinated to provide training, liability
      coverage, and deployment organization for hundreds of students representing
      multiple health professions. (Disaster Med Public Health Preparedness.
      2017;11:735-740).

PMID- 29070086
TI  - An assessment of Walk-over-Weighing to estimate short-term individual forage
      intake in sheep.
AB  - The main limitation for determining feed efficiency of freely grazing ruminants
      is measurement of daily individual feed intake. This paper describes an
      investigation that assessed a method for estimating intake of forage based on
      changes in BW of ewes. A total of 24 dry and non-pregnant Romane ewes (12
      hoggets, HOG; mean+/-SD 51.8+/-2.8 kg BW; body condition score (BCS) 2.6+/-0.2;
      and 12 adults, ADU; 60.4+/-8.5 kg BW; BCS 2.7+/-0.8) were selected for the study
      and moved from their rangeland system to a confined pen with controlled
      conditions and equipped with individual automatic feeders. The experiment lasted
      for 28 days (21 days adaptation and 7 days feed intake measurement). Ewes were
      fed hay and trained to use the electronic feeders (one feeding station per ewe)
      in which actual daily intake (H intake24) was measured. The pens were designed to
      maximize movement of trained ewes through an automated Walk-over-Weighing device,
      by using water and mineral salts as attractants. Total individual intake of hay
      measured in the automatic feeder at each meal (H intake) was compared with
      indirect estimates of feed intake determined using differences in the BW of the
      ewes (?BW) before and 1 h following morning and afternoon feeding at fixed times.
      The BW, BCS, H intake, H intake24, as well as plasma non-esterified fatty acids
      (NEFA), glucose and insulin profiles were determined. The BW was higher in ADU v.
      HOG but BCS was not affected by parity. The H intake24 was affected by day of
      experiment as a consequence of reduced availability and intake of water on one
      day. Plasma glucose, NEFA and insulin were not affected by parity or day of
      experiment. The H Intake was and ?BW tended to be higher in the morning in HOG,
      whereas H intake was and ?BW tended to be higher in ADU at the afternoon meal.
      Irrespective of parity or feeding time, there was very strong correlation (r
      2=0.93) between H intake and ?BW. This relationship confirms that our indirect
      method of estimating individual forage intake was reliable within the strictly
      controlled conditions of the present experiment. The method appears suitable for
      use in short-term intensive group feeding situations, and has potential to be
      further developed for longer-term forage intake studies, with a view to
      developing a method for freely grazing ruminants.

PMID- 29070087
TI  - Liver metabolism traits in two rabbit lines divergently selected for
      intramuscular fat.
AB  - Intramuscular fat (IMF) has a large effect in the sensory properties of meat
      because it affects tenderness, juiciness and flavour. A divergent selection
      experiment for IMF in longissimus dorsi (LD) muscle was performed in rabbits.
      Since liver is the major site of lipogenesis in rabbits, the objective of this
      work is to study the liver metabolism in the lines of the divergent selection
      experiment. Intramuscular fat content, perirenal fat weight, liver weight, liver
      lipogenic activities and plasma metabolites related to liver metabolism were
      measured in the eighth generation of selection. Direct response on IMF was 0.34
      g/100 g of LD, which represented 2.7 SD of the trait, and selection showed a
      positive correlated response in the perirenal fat weight. High-IMF line showed
      greater liver size and greater liver lipogenic activities of enzymes glucose-6
      phosphate dehydrogenase and malic enzyme. We did not find differences between
      lines for fatty acid synthase lipogenic activity. With regard to plasma
      metabolites, low-IMF line showed greater plasma concentration of triglycerides,
      cholesterol, bilirubin and alkaline phosphatase than high-IMF line, whereas high
      IMF line showed greater albumin and alanine transaminase concentrations than low
      IMF line. We did not observe differences between lines for glucose, total protein
      and plasma concentrations. Phenotypic correlations between fat (IMF and perirenal
      fat weight) and liver traits showed that liver lipogenesis affects fat deposition
      in both, muscle and carcass. However, the mechanisms whereby liver lipogenesis
      affected IMF content remain to be clarified.

PMID- 29070088
TI  - Effect of turmeric on the viability, ovarian folliculogenesis, fecundity, ovarian
      hormones and response to luteinizing hormone of rabbits.
AB  - The present study investigated whether dietary turmeric (Curcuma longa L.) can
      improve rabbit reproduction, ovarian function, growth, or viability. Female New
      Zealand White rabbits were either fed a standard diet (n=15) or a diet enriched
      with 5 g (group E1) or 20 g (group E2) turmeric powder per 100 kg feed mixture
      (n=16 or 15, respectively). After 295 days, weight gain, conception and kindling
      rates, pup and mother viability, ovarian macro- and micro-morphometric indices,
      release of leptin in response to the addition LH, and the release of
      progesterone, testosterone and leptin by isolated ovarian fragments were
      analyzed. Dietary turmeric failed to affect ovarian length and weight but did
      increase the number of primary follicles (E2: 32.5% greater than control group),
      as well as the diameter of primary (E1: +19.4%, E2: +21.1%), secondary (E2:
      +41.4%), and tertiary (E1: +97.1%, E2: +205.1%) follicles. Turmeric also
      increased the number of liveborn (E1: +21.0%) and weaned (E1: +25.0%) pups and
      decreased the number of stillborn pups (E2: -87.5%) but did not affect weight
      gain, conception, or kindling rate. Furthermore, dietary turmeric decreased doe
      mortality during the first reproductive cycle (13.3% in control; 0% in E1; and
      6.7% in E2) but not during the second cycle. In vitro, the ovaries of the
      turmeric-treated rabbits released more progesterone (E1: +85.7%, E2: +90.0%) and
      less testosterone (E2: -87.0%) and leptin (E2: -29.0%) than the ovaries of
      control rabbits. Moreover, LH decreased the leptin output of control rabbits but
      increased that of experimental rabbits. Therefore, it is likely that dietary
      turmeric improves pup viability and that it could promote rabbit fecundity by
      either (1) promoting the production of primary ovarian follicles or (2)
      stimulating the growth of follicles at all stages of folliculogenesis.

PMID- 29070089
TI  - Feed resource selection of Criollo goats artificially infected with Haemonchus
      contortus: nutritional wisdom and prophylactic self-medication.
AB  - Previous cafeteria studies suggested that a moderate natural gastrointestinal
      nematode (GIN) infection did not modify the resource selection of adult Criollo
      goats towards tannin-rich plants compared with worm-free goats. A higher
      infection with Haemonchus contortus could trigger a change in the resource
      selection behaviour towards tannin-rich foliage. Alternatively, goats might
      select plant species solely to meet their nutritional requirements. A cafeteria
      study investigated the effect of a high artificial infection with H. contortus on
      the feed resource selection of goats. Adult Criollo goats (37.5+/-4.8 kg BW) with
      browsing experience were distributed in two groups: the infected group (IG) with
      six animals artificially infected with H. contortus (6000 L3/animal); and the non
      infected group (NIG) with six animals maintained worm-free. The experiment
      included two 5-day periods with additional 5-day adaptation period. In the first
      period, animals were offered foliage of five plant species with a decreasing
      gradient of condensed tannins (CT) (Mimosa bahamensis, Gymnopodium floribundum,
      Havardia albicans, Acacia pennatula, Lysiloma latisiliqum), and three plant
      species with negligible CT content (Leucaena leucocephala, Piscidia piscipula and
      Brosimum alicastrum). In the second period the foliage of B. alicastrum was
      withdrawn. A grain-based concentrate feed was offered daily at 1% BW in DM basis.
      Dry matter and nutrient intake was determined. Foliage selection of each
      experimental group was determined using the Chesson selection index. The H.
      contortus egg count per gram of faeces (EPG) was determined for infected goats
      twice daily. Chesson index showed a similar pattern of foliage selection on
      periods 1 and 2. Mean EPG of goats in IG was 2028+/-259 EPG during period 1 and 1
      293+/-198 EPG during period 2 (P>0.05). During period 1, the selection pattern
      was highest for B. alicastrum (tannin-free), followed by a tannin-rich plant (M.
      bahamensis). These two plants remained as highly selected during period 2. The
      Chesson index showed that both experimental groups (IG and NIG) selected the same
      plant species in both periods. Thus, a high H. contortus infection did not affect
      selection of goats fed with CT-rich plants. Apparently, goats balanced their
      nutrient intake with the plants selected, showing evidence of nutritional wisdom.
      This balance may have helped to prevent excess protein in the diet and also to
      maintain a low GIN infection, both considered as examples of prophylactic self
      medication.

PMID- 29070090
TI  - Temperature alterations during embryogenesis have a sex-dependent influence on
      growth properties and muscle metabolism of day-old chicks and 35-day-old
      broilers.
AB  - Broiler eggs were either incubated at 37.8 degrees C during the whole incubation
      period (control), or at higher (38.8 degrees C, group H) and lower temperatures
      (36.8 degrees C, group L) from embryonic day (ED) 7 up to ED 10 (ED 7 to 10) or
      from ED 10 up to ED 13 (ED 10 to 13). Before and after this temperature treatment
      the eggs were incubated at 37.8 degrees C. The day-old chicks were weighted,
      sexed and fed up to day 35. On days 1 and 35 samples were taken from the breast
      and leg muscles for analyzing of the mitochondrial respiratory activity (MRA) and
      from the breast muscles for analysis of the cross-sectional areas (CSA) and the
      glycogen phosphorylase (GP), phosphofructokinase (PFK), lactate dehydrogenase
      (LDH), citrate synthase (CS) and cytochrome oxidase (COX) activities. Statistical
      analysis showed that treatment (control, group H, group L), sex and their
      interaction, but not the treatment period (ED 7 to 10; ED 10 to 13),
      significantly influenced the results. Group H chicks had lower (P?0.05) body and
      heart weights but higher (P?0.05) liver weights, CSA values, leg MRA as well as
      PFK, LDH, CS, GP and COX activities compared with the group L chicks. The results
      of the control chicks differ (P?0.05) from those of the group H (body, heart
      weight, COX), the group L chicks (liver weight, PFK, LDH, CS, GP) or the birds of
      both other groups (CSA). The group H broiler had higher (P?0.05) body and leg
      weights as well as LDH, CS, COX and GP activities than the group L broilers. The
      BWs and the LDH and GP results of the control broiler differ (P?0.05) from those
      of both other groups or from the results of the group H (CS) and group L broiler
      (COX). Female broilers had lower (P?0.05) body, breast and leg weights, but
      higher (P?0.05) CSA, LDH, CS and GP activities than the male animals. Analysis of
      treatment*sex interaction showed that group H hens had higher (P?0.05) body and
      breast weights, LDH and GP activities compared with the group L hens, whereas in
      the male broiler no effect of the interaction could be found, except for the
      lower (P?0.05) CSA values in the group H than group L cocks. The treatment
      effects are probably due to altered embryonic activity and related molecular
      mechanisms. The sex-related differences in the broiler indicate that these
      alterations already occur in the embryos and chicks, but become significant with
      the sexual dimorphism after hatch.

PMID- 29070091
TI  - How to fight terrorism? Political and strategic aspects.
AB  - "Fighting terrorism is like eating soup with a fork" (Shimon Peres). Peres's
      quote symbolically captures the key problem of countering terrorism. 9/11 proved
      to be a hallmark in the global perception of modern terrorism. The following
      questions form the framework of the present essay: What is the essence of modern
      terrorism? How did it develop during the past two decades? Who are the key
      players within the terror framework? What are the root causes for global
      terrorism? How are we to deal appropriately with the global phenomenon of
      terrorism? Are there any solutions (short-, medium-, long-term) to terrorism? If
      yes, where do we have to look for them? The underlying essay provides a strategic
      overview of antiterrorism policy that is based on the author's years-long
      experience as a high-level expert and advisor within the security policy
      framework. For this reason, citations are expressly not included. The key target
      audience comprises laypersons interested in the phenomenon of global terrorism
      and its social interplay.

PMID- 29070092
TI  - Late management of truncus arteriosus: 20 years of humanitarian experience.
AB  - OBJECTIVES: Early surgical management of common arterial trunk is well
      established and has good prognosis. Late diagnosis is less common. We reviewed
      late-diagnosed common arterial trunk management and prognosis for children in
      developing countries. We also discuss the need for prior catheterisation.
      Material and methods We reviewed all common arterial trunk patients managed by
      our humanitarian organization since 1996. RESULTS: A total of 41 children with
      common arterial trunk were managed at a mean age of 3 years old. The lack of
      adequate facilities in developing countries explains the late management. The
      decision to proceed with surgery was based on clinical and radiological symptoms
      of persistent shunt, particularly a high cutaneous saturation level, regardless
      of catheterization - not carried out systematically. Eight children had to be
      withdrawn and 33 (80.5%) received operation - mean saturation 91%. The
      postoperative course was marked by pulmonary arterial hypertension requiring
      specific treatment in 30% of cases. The operative mortality was 1/33. The 32
      children returned home without treatment after a mean post operative stay of 49
      days and were followed up (mean FU 3.4 years, none lost to follow-up). At last
      contact, 1 child died six months after surgery, 1 child had a massive truncal
      valve insufficiency, 5 had a significant stenosis of the RV-PA tube, and 2 have
      had further surgery for tube replacement. CONCLUSIONS: Late management and
      surgery of common arterial trunk is possible with good long-term results without
      prior hemodynamic examination up to an advanced childhood when signs of left-to
      right shunt persist. A high saturation level (above 88%) seems to be a good
      operability criterion.

PMID- 29070093
TI  - Properties and aromatic profile of dry-fermented sausages produced from
      Krskopolje pigs reared under organic and conventional rearing regime.
AB  - Krskopolje pig, the only Slovenian autochtonous breed is still relatively
      untapped, with almost no information available on the effect of rearing
      conditions or its aptitude for processing and meat product quality. In the
      present study, dry-fermented sausages were produced from Krskopolje pigs that
      were fed similar diets (with regard to ingredients, energy and protein content)
      but reared in either conventional (CON) or organic conditions (ECO). Sausage
      weight losses at the end of processing were recorded and their final pH, chemical
      composition (moisture, fat and protein content, proteolysis index, fat and
      protein oxidation, fatty acid and free fatty acid profile) were determined in
      addition to measurements of instrumental texture, sensory evaluation and volatile
      profile analysis. Compared with CON, ECO dry-fermented sausages had lower
      processing losses, lower pH, higher moisture, salt and thiobarbituric acid
      reactive substances content, less saturated fat and less free fatty acids.
      Volatile profile analysis showed that ECO dry-fermented sausages exhibited higher
      concentrations of compounds arising from lipid autooxidation and lower levels of
      volatile compounds resulting from microbial lipid beta-oxidation, amino acid
      degradation and spices. Panellists perceived ECO dry-fermented sausages as
      saltier and less colour intensive, while both rheological and sensory analysis
      indicated that ECO sausages had softer texture than CON. The present results
      indicate that rearing of Krskopolje pigs according to organic standards induced
      differences in meat and fat properties which affected the quality of dry
      fermented sausages, most distinctly in terms of softer texture and different
      volatile profile.

PMID- 29070094
TI  - Molecular systematics, biogeography, and colony fusion in the European dry-wood
      termites Kalotermes spp. (Blattodea, Termitoidae, Kalotermitidae).
AB  - European dry-wood termites belong to the genus Kalotermes (Kalotermitidae), one
      of the two termite genera in Europe. Until the recent description of two new
      species, Kalotermes italicus in Italy and Kalotermes phoenicae in the eastern
      Mediterranean area, Kalotermes flavicollis was the only taxon known in this
      region. The presence of additional entities, suggested by morphological and
      physiological variation observed in K. flavicollis, was supported by molecular
      studies revealing four distinct genetic lineages: lineage A, K. flavicollis sensu
      strictu, from the Aegean area to Italy; lineage B, in Tuscany; lineage SC, in
      Sardinia and Corsica; lineage SF, in southern France. Lineages A and B may form
      mixed colonies, suggesting hybridization. To draw a more detailed picture of
      Kalotermes evolution and biogeography in Europe, we analyzed samples from
      previously unsampled areas, such as Spain and southern Italy, by means of the
      highly informative cox1/trnL/cox2 mitochondrial DNA marker. Overall, phylogenetic
      analyses confirmed previously identified lineages and taxa, but widened the
      distribution of the lineage SC to the mainland and of the lineage SF to Spain and
      Portugal. Results further provided evidence for the synonymy between lineage B
      and K. italicus. Species delimitation analysis suggested that the three K.
      flavicollis lineages, as well as K. italicus, can be separate taxa. Data also
      suggest a possible interspecific hybridization between K. italicus and both K.
      flavicollis lineages A and SC.

PMID- 29070095
TI  - [MicroRNA-223 Regulates the Differentiation of Human Embryonic Stem Cells to
      Dendritic Cells].
AB  - OBJECTIVE: To establish a new inducing system for differentiation of human
      embryonic stem (ES) cells to dendritic cells (DC), and further explore how
      microRNA-223 (miR-223) regulates DC differentiation from ES cells. METHODS: Human
      ES cells were cultured on plates coated by IV type collagen and differentiated
      into hematopoietic stem/progenitor cells, common myeloid progenitor cells and DC
      step by step via adding different hematopoietic growth factors. The
      differentiated cells were identified by morphology, flow cytometry and
      hematopoietic colony forming unit (CFU) assays. Human ES cells were transfected
      with lentiviral vectors to overexpress miR-223 or inhibit miR-223 expression,
      then initiated the differentiation to DC. The differentiated cells at the
      different miR-223 levels were compared by the numbers of hematopoietic CFU and
      the expressions of specific surface markers. Dual-luciferase reporter assay was
      performed to test whether miR-223 directly targets TGFBR3. RESULTS: Human ES
      cells were successfully induced into DC as the percentage of CD83 was
      approximately 82%, and the expression of miR-223 was up-regulated during the
      whole process. Supplementing miR-223 level using synthetic miR-223 mimics
      improved the proportions of CD34+CD45+, CD34+CD45+ and CD83+ in differentiated
      cells, which were significantly higher than those in synthetic miR-223 inhibitor
      group and negative control (P<0.05). The expressions of cell makers at each
      differentiated phase in miR-223 inhibitor group were significantly lower than
      those in negative control (P<0.05). The differentiated cells in miR-223 mimics
      group showed approximately 759 CFUs per 105 cells, which was significantly higher
      than that in others (P<0.05). Compared with negative control, miR-223
      substantially inhibited the luciferase activity of Tgfbr3 3'UTR construct (by
      37%) (P<0.05). In addition, the luciferase activity of the mutant construct was
      significantly higher than that of the WT construct in the presence of miR-223
      mimics (P<0.05). With DC mature, the protein level of TGFBR3 gradually decreased
      using miR-223 mimics, and increased in miR-223 inhibitor group due to the
      suppression of the endogenous miR-223. CONCLUSION: MiR-223 promotes the
      differentiation of human ES cells to DC, probably through direet target to
      TGFBR3.

PMID- 29070096
TI  - [MiR-486 Regulates the Glycometabolism of Hematopoietic Cells by Targeting
      Sirt1].
AB  - OBJECTIVE: To investigate the effect and mechanism of miR-486 on glycometabolism
      of hematopoietic cells. METHODS: qRT-PCR was applied to detect the expression of
      miR-486 or Sirt1 on TF-1 cells under hypoxia. Lentivirus was used to mediate the
      overexpression or inhibition of miR-486 on TF-1 cells and qRT-PCR was used to
      detect the expressions of Sirt1, glucose transporter 1(Glut1) and glucose
      transporter 4(Glut4). Lentivirus-mediated Sirt1-shRNA transduction was used to
      knockdown Sirt1 expression which was detected by qRT-PCR and Western blot. The
      expressions of Glut1 and Glut4 were determined by qRT-PCR. RESULTS: Hypoxia
      promoted the expression of miR-486 and inhibited the expression of Sirt1. MiR-486
      overexpression could inhibit the expression of Sirt1 and promote the expressions
      of Glut1 and Glut4, whereas miR-486 silencing upregulated the sirt1 expression
      and inhibited the expressions of Glut1 and Glut4. And inhibition of Sirt1
      expression increased the expressions of Glut1 and Glut4. CONCLUSION: MiR-486 can
      regulate the glycometabolism of hematopoietic cells by targeting Sirt1.

PMID- 29070097
TI  - [In Vitro Identification and Characteristics of CD34- Leukemia Stem Cell in
      t(8;21) Acute Myeloid Leukemia].
AB  - OBJECTIVE: To preliminarily identify the existence of CD34- leukemia stem cell
      (LSC) in t(8;21) acute myeloid leukemia (AML) by in vitro test. METHODS: Bone
      marrow samples collected from newly diagnosed t(8;21) AML patients were tested.
      Lin-CD34+ CD38-(abbreviation, CD34+CD38-), Lin-CD34+CD38+ (abbreviation,
      CD34+CD38+) and Lin-CD34-CD38-CD45dimSSClow(abbreviation, CD34-"LSC") cell
      fractions were gated by flow cytometry after staining with fluorescent
      antibodies. Cells in G0 phase were identified through Hoechst 33342 and pyronin Y
      staining. Aldefluor reagent was used to test aldehyde dehydrogenase (ALDH)
      activity. The above-mentioned 3 cell fractions were sorted, and mRNA levels of
      AML1-ETO and WT1 were measured by real-time quantitative PCR. RESULTS: The 3
      tested samples displayed the same tendency in ratio of the cells in G0 phase:
      CD34-"LSC">CD34+ CD38->CD34+CD38+. The paired t-test of 53 patients showed that
      frequency of ALDHbr cells of both CD34+CD38- and CD34-"LSC" cell fractions was
      significantly higher than that of CD34+CD38+ (P<0.01), furthermore, the ALDHbr
      cell frequency was significantly higher in CD34-"LSC" than that in CD34+ CD38-
      (P<0.01). AML1-ETO mRNA levels of cells sorted from 3 patients were similar among
      the 3 cell fractions within each patient, whereas WT1 mRNA levels were
      significantly higher in CD34-"LSC" than that in other 2 cell fractions.
      CONCLUSION: CD34- LSC may exist in t(8;21) AML, and may be more primitive than
      CD34+ LSC. These results promote the necessity to perform in vivo xenogeneic
      transplantation mice.

PMID- 29070098
TI  - [Distribution of Type 9 T Helper Cells and Expression of Transcriptional Factors
      in Acute Myeloid Leukemia].
AB  - OBJECTIVE: To investigate the distribution of T helper (Th9) cells and its
      relationship with clinical characteristics of patients with acute myeloid
      leukemia (AML), and to analyze the activating levels of different transcriptional
      factors in Th9 cells. METHODS: The peripheral blood specimens of 102 AML patients
      and 83 healthy persons as controls were collected, then the T cells of peripheral
      blood in AML patients and controls were isolated by using CD3 magnetic beads, the
      mRNA expression of IL-9 was detected by real-time quantitative PCR, the
      Th9(CD4+IL-9+) cell levels in diffrent stages and activating level of Th9
      coexpression with IL-9 were detected by flow cytometry. RESULTS: The mRNA
      expression of IL-9 in peripheral blood of AML M2 and M3 patients was
      significantly higher than that in control groups (P<0.01), at same time the
      CD4+IL-9+ cell rate was significantly higher than that in control group
      also(P<0.01). The results of dynamically monitoring the distribution of Th9 cells
      in AML-M2 and M3 patients showed that the Th9 cell rate and the mRNA expression
      of IL-9 in newly diagnosed M2 and M3, and relapsed M2 groups were significantly
      higher than those of M2 and M3 in remission (P<0.01); the detection results of IL
      9- co-expression with transcriptional factors (SMAD3+, IRF-1+ and IRF-4+)
      indicated that the percantage of Th9 pSMAD3+ cells in peripheral blood of newly
      diagnosed and relapsed M2 and M3 patients was significantly higher than that in
      M2 and M3 patients in remission (P<0.01); on the contrary, the percentage of Th9
      IRF-1+ cells in peripheral blood of M2 and M3 patients in remission was
      significantly higher than that in newly diagnosed M2 and M3 patients (P<0.01).
      CONCLUSION: The distribution of T helper cells in peripheral blood of AML-M2 and
      M3 patients significantly increases, moreover, correlates with disease status.
      The prediction of Th9 cell functions should be performed in combination with it
      transcriptional factors which have inmportant significance for microenvironment
      of tumors in AML patients.

PMID- 29070099
TI  - [Expression of CXCR7 in Acute Monocytic Leukemia and Its Effects on THP-1 Cell
      Functions].
AB  - OBJECTIVE: To study the expression of stromal cell derived factor-1alpha (SDF
      1alpha) receptor CXCR7 in acute monocytic leukemia (AML-M5), and its effects on
      proliferation, apoptosis, invasion of acute monocytic leukemia cell line THP-1.
      METHODS: CXCR7 protein and mRNA expression levels in THP-1 cells and peripheral
      blood mononuclear cells (PBMNC) from the newly diagnosed AML-M5 patients and
      normal individuals were detected by flow cytometry, Western blot and RT-PCR
      respectively. CCK8, Annexin V/PI double staining and Transwell assay were used to
      observe the effects of CXCR7 on the proliferation, apoptosis, and invasion of THP
      1 cells in vitro. RESULTS: The expression of CXCR7 on immature cell surface of
      the newly diagnosed AML-M5 patients was significantly higher than that in the
      control group (P<0.05). CXCR7 was also highly expressed on THP-1 cells surface.
      The CXCR7 protein and mRNA levels in THP-1 cells and PBMNC of AML-M5 patients
      were significantly higher than those in the control group (P<0.05). The THP-1
      cell proliferation activity was higher in SDF-1alpha-treated group, but this
      activity could be inhibited by CXCR7 antibody (P<0.01). CXCR7 antibody did not
      affect THP-1 cell apoptosis (P>0.05). CXCR7 antibody could inhibit SDF-1alpha 
      induced THP-1 cell invasiveness (P<0.01). CONCLUSION: CXCR7 highly expresses in
      AML-M5 patients and THP-1 cells, and involves in cell proliferation and invasion.
      The blocking CXCR7 expression can reduce the risk of AML-M5 cell infiltration.

PMID- 29070100
TI  - [Comparison of Weak ABO Antigen and Normal ABO Antigen in Patients with Acute
      Leukemia].
AB  - OBJECTIVE: To compare the differences between weak ABO antigen patients and
      normal ABO antigen patients with acute leukemia, and to explore the clinical
      significance of weak ABO antigen in acute leukemia. METHODS: The ABO blood group
      was detected in 110 newly diagnosed acute leukemia patients(including 68 cases of
      AML and 42 cases of ALL) and 68 normal controls. Then the leukemia subtype, age,
      sex, laboratory test, risk status of leukemia patients, and DNA methylation of
      ABO promoter were compared between patients with weak and normal ABO antigen.
      RESULTS: The weak ABO antigen was found in patients with newly diagnosed acute
      leukemia, and was not found in ALL patients or normal group. No statistical
      differences were found in the distribution of ABO blood group, age,
      hepatosplenomegaly, lymphadenovarix, plt, precursor cell clusters derived from
      bone marrow, immunopheno-typing, LDH level, and risk status between AL patients
      of weak and normal ABO antigen groups (P>0.05). Compared with patients in normal
      ABO antigen group, the pateins in weak ABO antigen group had higher percentage of
      male(77.8% vs 30%), lower WBC(32.26*109/L vs 82.69*109/L) and Hb level(64.00 g/L
      vs 85.94 g/L) and higher DNA methylation level (18.91% vs 10.76%) (P<0.05).
      CONCLUSION: The cases of weak ABO antigen frequently appear in the male AML
      patients, the DNA methylation level of ABO gene promoter in patients with weak
      ABO antigen is significantly higher than that in patients with normal ABO
      antigen.

PMID- 29070101
TI  - [Methylation Status and mRNA Expression of DKK-3 and WIF-1 in Acute Myeloid
      Leukemia Patients].
AB  - OBJECTIVE: To analyze the promoter methylation status, mRNA expression and
      clinical significance of DKK-3 and WIF-1 genes in patients with acute myeloid
      leukemia(AML). METHODS: Methylation specific polymerase chain reaction (MS-PCR)
      mothod was carried out to detect DKK-3 and WIF-1 gene promoter methylation status
      in bone marrow specimen from 56 patients with AML and 20 patients with iron
      deficiency anaemia(IDA) as control; then the real-time quantitative reverse
      transcription polymerase chain reaction (RT-PCR) was used to detect mRNA
      expression of DKK-3, WIF-1 gene and beta -catenin in the above-mentioned
      specinens, and their relationship with the clinical features and survival time
      was analyzed. RESULTS: The promoter methylation rate of DKK-3 and WIF-1 gene in
      AML patients were significantly higher than that in control
      group(chi2=15.330,P<0.001; chi2=17.371,P<0.001). There was no relationship
      between DKK-3 and WIF-1 gene promoter methylation rate and AML patient's sex,
      age, clinical typing. The relative expression of DKK-3 and WIF-1 gene mRNA in AML
      group were 0.840+/-0.320 and 0.792+/-0.313, which were lower than those in
      control group (1.134+/-0.392 and 1.047+/-0.334) respectively, the difference was
      statistically significant (t=3.415,P=0.000; t=3.070, P=0.003). The relative
      expression of beta-catenin mRNA in AML bone marrow specimens in AML group was
      0.756+/-0.304, which was higher than that in control group(0.342+/-0.105), the
      difference was statistically significant (t=5.943, P=0.001). The expression of
      DKK-3 and WIF-1 gene mRNA negatively correlated with beta-catenin mRNA(r=-0.543;
      r=-0.562). Kaplan Meier survival curve analysis showed that overall survival time
      in AML patients with DKK-3 gene methylation was shorter than that in the AML
      patients with DKK-3 gene unmethylation(chi2=3.957, P=0.042). Futhermore, the
      orerall survival time in AML patients with WIF-1 gene methylation was also
      shorter than that in AML patients with WIF-1 gene unmethylation (chi2=4.520,
      P=0.029). CONCLUSION: Wnt/beta-catenin signaling pathway is abnormally activated
      in AML patients, the DKK-3 and WIF-1 gene promoter methylation may be involved in
      Wnt pathways activation and the pathogenesis of AML.

PMID- 29070102
TI  - [Expression and Clinical Significance of Focal Adhesion Kinase in Patients with
      Acute Leukemia].
AB  - OBJECTIVE: To explore the expression of focal adhesion kinase (FAK) in patients
      with acute leukemia (AL) and its clinical significance. METHODS: The FAK mRNA
      levels in leukemic cells of 50 patients with AL and bone marrow mononuclear
      cells(BMMNC) of 10 healthy controls were measured by semi-quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR). The bone marrow cell
      chromosomes were prepared using direct and short term culture, and karyotyping
      was performed by R-banding technique. RESULTS: The expression positive rate of
      FAK mRNA in leukemic cells of 50 patients with AL was 66.0%, which was
      significantly higher than that in normal controls (20.0%) (P<0.05). The
      expression positive rates and levels of FAK mRNA in both ALL and ANLL cells were
      statistically significantly higher than those in normal controls (P<0.05), but
      the difference between ALL and ANLL cells was not significant (P>0.05). All the
      expression- positive rates and levels of FAK mRNA in newly diagnosed AL patients
      and the relapsed AL patients were significantly higher than those in normal
      controls (P<0.05), but the difference between the newly diagnosed AL patients and
      the relapsed AL patients was not significant (P>0.05). Morecover, the expression
      plsitive rate and levels of FAK mRNA in the remitted patients were lower than
      those in newly diagnosed and relapsed patients (P<0.05), but were no
      statistically significantly different from normal controls (P>0.05). The
      expression- positive rate and level of FAK mRNA in the AL patients with abnormal
      karyotype were significantly higher than those in the AL patients without
      abnormal karyotype (P<0.05). CONCLUSION: FAK mRNA over-express in the leukemia
      patients, which may be related with the outome of disease, possibly providing
      novel targeting sites for the treatment of leukemia.

PMID- 29070103
TI  - [Knockout of LSD1 Gene by CRISPR/Cas9 System Significantly Inhibited
      Proliferation and Expression of CD235a in K562 Cells].
AB  - OBJECTIVE: To study the effect of LSD1 knock-out on human chronic myeloid
      leukemia cells(K562 cells). METHODS: The LSD1 gene in K562 cells was knocked-out
      specifically by using CRISPR/Cas9 system, the single cells were gained by flow
      cytometric sorting technique, the LSD1+/- and LSD1-/- cell lines were gained
      after amplificantion and culture, identification of Western blot and sequencing.
      The MTS assay was used to detect the effect of LSD1 knockout on the proliferation
      of K562 cells, the flow cytometry was used to examine the expression of K562 cell
      surface marker after LSD1 knockout. RESULTS: The LSD1 stable knockout cell line
      of K562 (LSD1+/- and LSD1-/-)were successfully costructed. It was found that
      knockout of LSD1 significantly inhibited the proliferation of K562 and the
      expression of CD235a. CONCLUSION: LSD1 plays a key role in the regulation of K562
      cell proliferation and CD235a expression.

PMID- 29070105
TI  - [Embelin Reverses the Multi-drug Resistance of K562/D to Daunorubicin
      Independently of P-gp and MDR1 mRNA].
AB  - OBJECTIVE: To investigate the mechanism of reversing drug resistance of K562/D
      cells to daunorubicin by Embelin and its relationship with P-gp and MDR1 mRNA.
      METHODS: MTT assay was used to detect and compare the cell proliferation rate of
      treating with DNR alone and DNR combined with Embelin. Flow cytometry with
      Annexin V-FITC/PI double staining was used to detect cell apoptosis rate, Western
      blot was used to detect the expression of XIAP,Caspase-3,BCL-2,BAX and P-gp of
      K562/D cells after using DNR alone and combining with Embelin. Quantitative real
      time PCR was used to detect XIAP,BCL-2,BAX and MDR1 mRNA. RESULTS: The IC50 of
      K562 and K562/D cells treated with DNR for 24 h were 2.177 ug/ml and 69.43 ug/ml,
      respectively. The drug-resistance index was 31.89; The proliferation inhibition
      rates of K562/D cells treated with Embelin of 3, 10, 30, 100 and 300 ug/ml for 24
      h were 2.70%+/-1.08%, 10.92%+/-4.89%, 28.13%+/-2.09%, 36.56%+/-3.24% and 43.59%+/
      1.16%; The proliferation inhibition rates of K562/D cells treated with DNR of
      0.1, 1, 10 and 100 ug/ml combined with 10 ug/ml Embelin for 24 h were 31.92%+/
      3.29%, 49.57%+/-6.87%, 55.16%+/-0.78% and 71.94%+/-3.89%. The IC50 was 2.11 ug/ml
      respectively. The reverse index was 32.91. The apoptosis rates of K562/D cells
      treated with 0.1 ug/ml DNR alone or combined with Embelin of 10 ug/ml and 30
      ug/ml for 24 h were 12.06%+/-0.95%, 27.54%+/-0.59% and 39.59%+/-1.57%,
      respectively. The results of Western blot showed that after combination of DNR
      with Embelin, the expression of Caspase-3 was significantly down-regulated
      (P<0.05), moreover, the prolifiration inhibition effect of drug combination on
      cells could be countreacted by Z-VAD-FMK, at the same time the expression of XIAP
      and BCL-2 protein was significantly down-regulated(P<0.05), the expression of BAX
      protein was significantly up-regulated(P<0.05), while there was no change of P-gp
      expression later (P<0.05). The results of RT-PCR showed that after combination of
      DNR with Embelin, expression of XIAP and BCL-2 mRNA was significantly down
      regulated(P<0.05), expression of BAX mRNA was significantly up-regulated(P<0.05),
      while there was no obvious change of MDR1 mRNA expression(P>0.05). CONCLUSION:
      The down-regulation of XIAP contributes to enhance the effect of DNR on K562/D
      cells, the mechanism of Embelin-reversing the drug-resistence of K562/D cells to
      DNR does not relate with P-gp and MDR1 mRNA.

PMID- 29070104
TI  - [Effects of DOT1L Inhibitor EPZ-5676 Combined with Chemotherapeutic Drugs on
      Prolifiration and Apoptosis of RS 4;11 Cells].
AB  - OBJECTIVE: To investigate the synergistic antiproliferative and inducing
      apoptotic effect of EPZ-5676 combined with chemotherapeutic drugs on acute
      lymploblastic leukemia(ALL). METHODS: The MLL rearragement positive (MLL-r+) ALL
      cell line RS4;11 was treated with EPZ-5676 alone and its combination with 5 kinds
      of chemotherapeutic drugs of ALL, the CCK-8 method was used to assay the
      inhibitory rate of leukemia cells treated with EPZ-5676 and chemotherapeutic
      drugs alone and their combination; the compusyn software was used to evaluate the
      relationthip between inhibitory rate (Fa) of combined drugs for leukemia cells
      and combination index (CI), and to determine the interaction of drugs; the flow
      cytometry with Annexin V-FITC/PI double staining was used to detect the apoptotic
      rate of RS4;11 treated EPZ-5676, GC, VCR, CTX, epirubicin and VP16 alone and
      combination of EPZ-5676 with them and to compare the inducing apoptotic effect of
      combined drugs. RESULTS: The combination of EPZ-5672 with GC or VCR or VP16
      showed synergistic antiproliferative effect; the combination of EPZ-5676 with TX
      or epirubicin displayed antogonistic effect. As compared with blank control
      group, 5, 10 and 25 umol/L EPZ-5676 did not affected on apoptosis of RS4;11
      cells, but 5 umol/L EPZ-5676 combined with VCR of GC possessed synergistically
      inducing apoptotic effect (56.87% vs 12.93%)(P<0.01), (8.86% vs 5.28%)(P<0.05).
      CONCLUSION: The EPZ-5676 combined with GC or VCR or VP16 possesses synergistic
      antiproliferative effect on RS4;11 cells, the effect of EPZ-5676 alone on
      apoptosis of RS4;11 cells is no significant, but the combination of low
      concentration EPZ-5676 with VCR or GC displays synergistically inducing apoptotic
      effect.

PMID- 29070106
TI  - [Sensitivity of AML Cells with FLT3- to PKC412 In Vitro].
AB  - OBJECTIVE: To explore the clinical value of PKC412 (midostaurin) in treatment of
      AML patients with FLT3-. METHODS: The bone marrow or peripheral blood were
      collected and heparinized from 21 newly diagnosed FLT3- AML patients, then the
      mononuclear cells from bone marrow or peripheral blood were isolated by density
      gradient method. The sensitivity of leukemia cells to PKC412 of 8 concentration
      in vitro was detected by ATP-bioluminescence-tumor chemosensitivity assay (ATP
      TCA), and the relationship among sensitivity results in vitro, risk
      stratification and therapeutic efficacy was analyzed. RESULTS: The leukemia cells
      of 21 patients with AML displayed different sensitivities to PKC412 in vitro. The
      rate of sensitivity in vitro was 42.9%, and sensitive concentration in vitro were
      between 1 umol/L and 5 umol/L. There was no significant relationship between risk
      stratification and sensitivity results of PKC412 in vitro. There was also no
      significant relationship between clinical efficacy and sensitivity results of
      PKC412 in vitro. The survival of patients in low-risk and intermediate-risk
      groups was better than that of patients in high-risk groups (P=0.015).
      CONCLUSION: PKC412 can be one of the effective therapeutic method for AML
      patients without FLT3 mutation. The sensitivity of leukemia cells to PKC412 may
      become a prognostic marker for evaluating clinical efficacy of PKC412, which is
      independent of other factors.

PMID- 29070107
TI  - [Clinical Analysis of 7 Children with Mature B-cell Acute Lymphoblastic
      Leukemia].
AB  - OBJECTIVE: To evaluate the efficacy of CCCG-BNHL-2015 protocol in treatment of
      children with mature B-cell acute lymphoblastic leukemia (mature B-ALL). METHODS:
      Seven pediatric patients with newly diagnosed mature B-ALL were treated by CCCG
      BNHL-2015 protocol (risk group R4) in Children's Hospital of Nanjing Medical
      University from November 2014 to January 2017. RESULTS: The median age of
      patients at initial diagnosis was 7.2 years (range 4.1 to 11.75 years) with a
      male predominance (5:2), the clinical characters were as follows: 4 cases
      combined with thoracic and/or abdominal lumps, only lymphonode was involved in 1
      case, bone destruction was complicated in 2 cases and 1 case was complicated with
      central nervous system leukemia. In 2 children, tumor lysis syndrome appeared at
      early phase. The lactate dehydrogenase level at diagnosis of all patients
      extremely increased. All patients achieved complete remission after 2 to 4
      courses of therapy. Two among them underwent autologous hematopoietic stem cell
      transplantation. One with primary central nervous system leukemia relapsed before
      the last course, then the treatment was abandoned. The rest of 6 patients
      survived with a median follow-up period of 14 months (ranged from 7 to 28
      months), and suffered from different degrees of myelosuppression and infection.
      No one died from serious complications. CONCLUSION: The CCCG-BNHL-2015 protocol
      (risk group R4) shows better curative effect, higher safety and remission rate in
      childhood mature B-cell lymphoblastic leukemia.

PMID- 29070108
TI  - [Anti-Tumor Effect of Rigosertib on HEL and K562 Cells and Its Related
      Mechanism].
AB  - OBJECTIVE: To investigate the effects of rigosertib on the apoptosis,
      proliferation and cell cycle of HEL and K562 cells. METHODS: The HEL and K562
      cells were treated with different concentration of rigosertib at different time
      points, the cell apoptosis, proliferation and cycle were determined by using flow
      cytometry with Annexin V/PI double staining, WST-1 method and 7-AAD assay,
      respectively. Intracellular signaling proteins were detected by flow cytometry
      (FCM). RESULTS: Rigosertib induced obvious apoptosis in HEL and K562 cells, and
      the apoptotic effect was both time-dependent and dose-dependent manner (P<0.05).
      The low dose of rigosertib inhibited obviously the proliferation of HEL and K562
      cells after treatment from 6 to 54 h, Rigosertib arrested HEL and K562 cells into
      G2/M phase. In addition, Rigosertib obviously increased the expression of
      apoptosis-related proteins such as cleaved caspase 3 and PARP, and reduced the
      proliferation-related proteins such as BCL-2 and Cyclin D1. Rigosetib inhibited
      the activation of AKT-GSK signaling through decreasing the expression of AKT,
      pAKT(Ser473) and GSK-3alpha/beta (S21/9). CONCLUSION: Rigosertib inhibites
      proliferation, induces apoptosis and cell cycle arrest in G2/M phase of HEL and
      K562 cells. This agent may have potential application prospect in leukemia
      therapy.

PMID- 29070109
TI  - [Correlation of SOCS3 mRNA Expression Level with Clinical Characteristics and
      Early Response to Treatment in Pediatric Acute Lymphoblastic Leukemia].
AB  - : Obejective: To investigate the expression level of suppressor of cytokine
      signaling SOCS3 mRNA in children's acute lymphoblastic leukemia(ALL); to analyze
      the relationship between the expresion level of SOCS3 mRNA and disease status and
      risks of ALL, and to explore the application of SOCS3 mRNA in evaluation of ALL
      disease status, risk and target therapy. METHODS: The expression levels of SOCS3
      mRNA in bone marrow mononuclear cells from 45 cases of newly diagnosed ALL at
      initial diganosis and induction remission and 13 normal children as controls were
      detected by SYBR Green fluorescence quantitative PCR; the correlation of SOCS3
      mRNA expression level with risk and clinical characteristics of ALL was analyzed
      by means of statistical method; the immunofluorescence histochemistry method and
      laser confocal microscopy were used to detect the sites and expression level of
      SOCS3 mRNA in bone marrow samples of ALL patients. RESULTS: The SOCS3 mRNA
      expression level at initial diagnosis of 45 ALL patients was significantly lower
      than that of normal controls (P<0.05), and that in induction remission of 45
      patients was not significant different from normal controls (P<0.05); the SOCS3
      mRNA expression level at initial diagnosis of patients with standasd and high
      risk was higher than that of patients with low risk (P<0.05). The 45 patients
      were divided into high expression and low expression groups according to SOCS3
      mRNA expression level at initial diagnosis by median method, comparison of
      clinical characteristics in 2 groups was found that the SOCS3 mRNA high
      expression group had even more higher leukocyte count in peripheral blood, even
      more higher LDH level and much more poor prognostic genes; in addition, the high
      expression group showed more higher risk in comparison between 2 group.
      CONCLUSION: The SOCS3 mRNA expression is down-regulated at initial diagnosis,
      while recovered to normal level after induction remission of disease, thus the
      SOCS3 can be used as an indicator for evaluation of disease status. The high
      expression of SOCS3 mRNA up-regulates the disease risk, therefore the SOCS3 mRNA
      can be used as a factor for evaluation of ALL risk. The treatment of ALL via
      regulation of SOCS3 mRNA expression level maybe can become a new way. The
      regulation of SOCS3 mRNA expression level maybe can become a new way for
      treatment of ALL.

PMID- 29070110
TI  - [Effect of Over-Expression of KLF4 on the Proliferation and Apoptosis of K562
      Cells In Vitro].
AB  - OBJECTIVE: To study the effect of over-expression of KLF4 on the proliferation
      and apoptosis of K562 cells. METHODS: The recombinant plasmid with over
      expression of KLF4 was transfected into K562 cells by electroporation, then the
      obtained G418-resistant clones of K562 cells (K562/pEGFP-KLF4) were used as
      experimental group, and the vector control (K562/pEGFP-C1) and blank K562 cell
      control groups were set up at the same time. The expression of EGFP-KLF4 fusion
      protein in K562 cells was observed by fluorescence microscopy; the Western blot
      was performed to detect the level of KLF4 protein in the cells of each groups,
      the cell proliferation was tested by methylthiazolyl tetrazolium (MTT) assay, and
      the cell apoptosis was detected by flow cytometry. RESULTS: Compared with
      K562/pEGFP-C1 group and blank K562 group, the level of KLF4 protein of K562/
      pEGFP-KLF4 cells were significantly increased, and the over-expression ratio
      reached 74.07%(P<0.05). The proliferation ability of the over-expressing KLF4
      K562 cells was inhibited significantly (P<0.05). However, the apoptosis of
      K562/pEGFP-ILK cells with over-expression of KLF4 was increased (P<0.05).
      CONCLUSION: A stable over-expressing KLF4 protein K562 cell line with was
      constructed successfully, and the over-expression of KLF4 can inhibi
      proliferation and promote apoptosis of K562 cells.

PMID- 29070111
TI  - [Anti-Leukemia Effect and Mechanism of Oridonin on Imatinib-Sensitive and
      Imatinib-Resistant K562 Cells].
AB  - OBJECTIVE: To explore the molecular mechanism of resistance to imatinib in K562
      cells(K562-R) and the anti-proliferative effect of oridonin (OR), as well as its
      mechanism in imatinib-sensitive and imatinib-resistant K562 cells (K562-S and
      K562-R cells). METHODS: The expression of p-Lyn in K562-S and K562-R cells were
      detected by Western blot. The anti-proliferative effect of OR in K562-S and K562
      R cells was assayed by MTT, the morphological changes were examined with
      microscope, the cell apoptosis was detected by flow cytometry, the expressions of
      BCL-2 and Akt/mTOR signaling pathway were detected by Western blot. RESULTS: The
      over-expression of p-Lyn was detcected in K562-R cells, OR inhibited the
      proliferation of K562-S and K562-R cells and the value of IC50 was 4.23+/-1.30,
      4.97+/-2.23 umol/L, respectively. The apoptotic rate was obviously enhanced after
      OR treatment for 24 h, compared with control group. OR down-regulated the
      expression of p-Lyn, mTOR signaling pathway and BCL-2 protein. CONCLUSION: Over
      expression of p-Lyn may be involved in the mechanism of resistance to imatinib.
      OR can inhibit the proliferation of K562-S and K562-R cells through down
      regulating p-Lyn, inhibiting mTOR signaling pathway and down-regulating
      expression of BCL-2 protein.

PMID- 29070112
TI  - [Expression and Significance of PD-L1, HSP90 and HSP90alpha in Serum of Patients
      with Acute Leukemia].
AB  - OBJECTIVE: To explore the expression and clinical significance of PD-L1, heat
      shock protein 90 (HSP90) and HSP90alpha in the serum of patients with acute
      leukemia (AL) of different types and disease stages. METHODS: A total of 84 AL
      patients from January 2013 to October 2016 in our hospital and 20 healthy persons
      as controls were selected. All the samples of serum or bone marrow were
      separated. The protein expression levels of serum HSP90, HSP90alpha were detected
      by ELISA. The flow cytometry was used to detect PD-L1 expression. The
      relationship of the expression level of PD-L1, HSP 90, and HSP90alpha with
      clinical outcome was analyzed. RESULTS: The expression levels of serum HSP90,
      HSP90alpha and PD-L1 positive rate in AL patients were significantly higher those
      that in control group (P<0.05), the expression levels of serum HSP90, HSP90alpha
      and PD-L1 positive rate of Al patients in remission were lower than those in
      newly diagnosed patients (P<0.05). The expression level of HSP90, HSP90alpha and
      PD-L1 positive rate in the relapsed AL patients were higher than those in newly
      diagnosed AL patients and patients in remission (P<0.05). There was no
      significant difference of HSP90 protein level and PD-L1 positive rate between
      newly diagnosed AML patients and ALL patients(P>0.05). HSP90alpha level of newly
      diagnosed AML patients was lower than that in newly diagnosed ALL (P<0.05).
      HSP90alpha and HSP90 levels and PD-L1 positive rate in no remission patients were
      significantly higher than those in complete remission patients (P<0.05). The
      HSP90alpha level in patients without recurrence decreased during chemotherapy.
      The HSP90alpha protein level was the lowest after the hematopoietic stem cell
      transplantation, but increased after relapse. CONCLUSION: The PD-L1,HSP90 and
      HSP90alpha play an important role in the developmental process of acute leukemia,
      which can be used as reference indications to assess clinical efficacy and
      prognosis.

PMID- 29070113
TI  - [Retrospective Analysis of Clinical Features and Prognosis of 84 Patients with
      Extranodal NK/T Cell Lymphoma in One Center].
AB  - OBJECTIVE: To investigate the clinical characteristics, treatment and prognostic
      factors of patients with extranodal NK/T cell lymphoma. METHODS: The clinical
      data of patients with extranodal NK/T cell lymphoma admitted in the Hospital
      Affiliated to the Academy of Military Medical Science from June 2006 to June 2016
      were retrospectively analyzed. The clinical features, therapeutic efficacy and
      prognosis-related factors were clarified. RESULTS: A total of 84 patients with
      extranodal NK/T cell lymphoma with complete clinical data were collected, with a
      median follow-up of 21 months (1-123 months), the overall survival (OS) and
      progression free survival (PFS) were 58.9% and 52.1% years, respectively.
      Univariate analysis showed that anemia, the copy number of EBV-DNA, LDH level,
      IPI score, ECOG score, Ann Arbor staging, complete remission after the initial
      therapy were statistically significant for both OS and PFS of the patients, and
      chemotherapy regimens were only statistically significant for PFS. Multivariate
      analysis showed that complete remission after the initial therapy, LDH level and
      ECOG score were statistically significant for both OS and PFS in patients with
      NK/T cell lymphoma. CONCLUSION: LDH level, ECOG score and complete remission
      after the initial therapy are independent prognostic factors for patients with
      extranodal NK/T cell lymphoma.

PMID- 29070114
TI  - [Effects of mTOR Inhibitor Rapamycin on Burkitt's Lymphoma Cells].
AB  - OBJECTIVE: To explore the effects of mTOR inhibitor rapamycin on proliferation,
      cell cycle and apoptosis of Burkitt's lymphoma cell line Raji and CA46 cells and
      its mechanism, so as to provide the experimental evidence for a therapeutic
      target of Burkitt's lymphoma. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide(MTT) assay was performed to assess the inhibitory
      effect of rapamycin on proliferation of Burkitt's lymphoma cell line Raji and
      CA46 cells. The cell cycle distribution of Raji and CA46 cells was analyzed by
      flow cytometry with propidium iodide(PI) single staining. The cell apoptosis of
      Raji and CA46 cells was analyzed by flow cytometry with FITC Annexin V+PI double
      staining. The expressions of RPS6, p-RPS6, survivin and caspase-3 proteins were
      detected by Western blot after treating with rapamycin. RESULTS: Rapamycin
      markedly inhibited the proliferation of both Raji and CA46 cells in a time- and
      concentration-dependent manners, showing good biological activity, the cell
      proliferation inhibition rate reached about 20% after treatment with 1 nmol/L
      rapamycin. After treatment with different concentrations of rapamycin for 24 and
      48 hours, the proportion of both cells in G1/G0 phase in the treated groups was
      significantly increased in a time- and concentration-dependent manners in
      comparison with the solvent control group. With regard to the cells in S and G2/M
      phase, the decreased population was accompanied by the increase of G1/G0 phase
      cells. After treatment with 100 nmol/L rapamycin for 48 hours, both Raji and CA46
      cells demonstrated an apparent apoptosis,especially late apoptosis by flow
      cytometry with Annexin V+PI staining. After treatment with rapamycin, the
      expression of p-RPS6 and survivin of Raji and CA46 cells was obviously down
      regulated, the expression of caspase-3 was obviously up-regulated in a time- and
      dose-dependent manners. However, rapamycin did not obviously affect the
      expression of RPS6. CONCLUSION: The rapamycin can effectively inhibit cell
      proliferation, arrest Raji and CA46 cells in G1/G0 phase, and this effect
      associates with inhibiting the activation of mTOR/RPS6 signal pathway through
      down-regulating the expression of phosphorylated RPS6, i.e. mTOR downstream
      signal pathway. It also can induce apoptosis by down-regulating the expression of
      anti-apoptotic protein survivin and activating the intrinsic pro-apoptotic
      protein caspase-3.

PMID- 29070115
TI  - [Curative Efficacy of High Dose MTX Combined with Rituxan for Treatment Primary
      CNS Lymphoma].
AB  - OBJECTIVE: To explore the curative efficacy of methotrexate(MTX) combined with
      rituxan for treating patients with primary central nervous system(CNS) lymphoma.
      METHODS: One hundred patients with primary CNS lymphoma in our hospital were
      randomly divided into targeted treatment group(50 cases) and traditional
      treatment group (50 cases). Targeted treatment group adopted the therapy of high
      dose methotrexate combined with rituxan, the traditional treatment group adopted
      the high-dose methotrexate combined with whole brain radiotherapy. The results of
      relevant imaging examination, clinical data, imaging, follow-up and the survival
      time were analysed and compared between these 2 groups. RESULTS: In the targeted
      therapy group, there were 33 cases in CR, 9 cases were in stable condition, and 5
      cases were in partial response, and 3 cases in the progressive stage. In the
      group of traditional treatment group, 29 cases reached complete remission, 5
      cases were in stable condition, 11 cases were in partial response, and 5 cases
      were in the progressive stage. In the targeted treatment group and traditional
      treatment group, the median progression-free survival time was 28 and 11 months,
      respectively. CONCLUSION: The first choice for treatment scheme of PCNSL is high
      dose methotrexate chemotherapy combined with whole brain radiotherapy, that
      showed a certain curative effect, but the adverse reactions are larger, and a big
      late neuro toxic reaction may occur, while high-dose methotrexate combined PCNSL
      rituxan treatment shows high curative effect, less adverse reaction and low side
      effects. This treatment also has a more positive value for the elderly patients
      with PCNSL.

PMID- 29070116
TI  - [Effect of B Cell Differentiation Markers on the Prognosis of Primary Central
      Nervous System Lymphoma].
AB  - OBJECTIVE: To investigate the value of B-cell differentiation markers in
      prognosis evaluation of 119 patients with primary CNS lymphoma(PCNSL). METHODS:
      The expressions of BCL-2, BCL-6, CD10 and MUM1/IRF4 protein were determined by
      immunohistochemistry, and their relationship with the prognosis of primary
      central nervous system lymphoma was analyzed. RESULTS: Univariate analysis showed
      that BCL-6 positive means shorter PFS (P=0.047) and OS (P=0.035). Multivariate
      analysis showed that BCL-6 positive expression was related with shorter PFS
      (hazard ratio:1.95, 95% CI: 1.22- 3.12, P=0.005), but did not relate with OS
      (hazard ratio: 1.85, 95% CI: 0.71- 4.80, P=0.21). Classification based on Hans
      algorithm and expression status of the single B-cell markers BCL-2, CD10 and
      MUM1/IRF4 did not correlate with prognosis. CONCLUSION: BCL-6 may be an
      unfavorable prognostic biomarker for PCNSL.

PMID- 29070118
TI  - [Analysis of Clinical Efficacy and Influencing Factors of Gemcitabine-L
      Asparaginase-Oxaliplatin Chemotherapy Scheme and Radiotherapy for Treatment of
      Early ENKTL Patients].
AB  - OBJECTIVE: To analyse the clinical efficacy and its influencing factors of early
      ENKTL patients received chemotherapy of gemcitabine-L-asparaginase-oxaliplatin
      (GELOX) scheme and radiotherapy. METHODS: The clinical data of 80 cases of early
      nasal type NK/T cell lymphoma treated during May 2013 to May 2016 were analyzed
      retrospectively. The earty ENKTL patients were divided into 3 groups: group I (50
      cases) with GELOX after chemotherapy combined with radical radiotherapy, group II
      (16 cases) with GELOX after other chemotherapy combined radical radiotherapy,
      group III (14 cases) patients only received GELOX chemotherapy. The average cycle
      of chemotherapy was 3 cycles, and the total dose of irradiation was 50.20+/- 3.50
      Gy/(20-30 times). RESULTS: After the treatment of 80 early ENKTL patients, the CR
      rate of patients was 67.50% (54/80); the CR rate of patients in I, II, III groups
      received chemotherapy was 45%, 10%, 18% rate respectively (P=0.029). The 2 years
      PFS of the 80 paaients was 79%,and 2 year OS rate was 85.00%; the 2 year PFS rate
      and OS rate in group 1 and 3 were 84% and 92.00%. The 2 year OS rate, PFS rate in
      group 1 (96%, 84%) were higher than that in group 3 (47%, 40.00%)(P=0.045,0.003)
      and group II (50%, 45%, P=0.001,0.00); the OS rate and PFS rate in group 2 and 3
      were not statistically significant different (P=0.220,0.97). The factors that
      affect OS and PFS were remission or not remission after chemotherapy. CONCLUSION:
      Clinical use of GELOX induction chemotherapy combined with radical radiotherapy
      in the treatment of early ENKTL can achieve good therapeutic results.

PMID- 29070117
TI  - [Efficacy Analysis of GEMOX Regimen for Treatment of Refractory Non-Hodgkin's
      Lymphoma].
AB  - OBJECTIVE: To explore the clinical efficacy of GEMOX regimen on patients with
      refractory non-hodgkin's lymphoma. METHODS: Eighty-two cases of non-Hodgkin's
      lymphoma were divided into 2 groups: gemcitabine+oxaliplation(Gem+Oxa) group (42
      cases) and vinorelbine+oxaliplatin(Vin+Oxa) group (40 cases) according to
      chemotherapy regimens. The clinical efficacy, side effects, progression-free
      survival situation in 2 groups were compared. RESULTS: There was no significant
      difference on the clinical effects of 2 groups (P>0.05); The therapeutic efficacy
      for B cell lymphoma was higher than that for T cell lymphoma(P<0.05); The
      therapeutic effects for I-II stages was lower than that for III-IV
      stages(P<0.05); The incidences of platelet decline, nausea and vomit, peripheral
      nerve symptoms in Gem+Oxa group were lower than those in Vin+Oxa group(P<0.05);
      There was no significant difference in the median progression free
      survival(P>0.05). CONCLUSION: The efficacy of GEMOX regimen for refractory non
      Hodgkin's lymphoma has been confirmed to be good, it has distinct clinical
      curative effect, it can prolong the progression-free survival time in patients
      with B cell lymphoma, specially for III-IV stages. It can be used as the
      preferred method for the treatment of patients with refractory NHL.

PMID- 29070119
TI  - [Anti-proliferation Effect of NS-398 in Combination with Bortezomib on Multiple
      Myeloma RPMI 8226 Cells In Vitro].
AB  - OBJECTIVE: To investigate if NS-398 could enhance the chemosensitivity of
      Bortezomib (BOR) on human multiple myeloma RPMI 8226 cells. METHODS: After the
      treatment of NS-398 combined with BOR, MTT assay was used to detect the
      proliferation inhibition effect on human multiply myeloma RPMI 8226 cells in
      vitro, Flow cytometry was used to analyze their effect of apoptosis and cell
      cycle; the caspase-3 activity of different treatment group was detected by using
      ELISA and the activity of Cox-2 was measured by using Cox-2 activity assay kit.
      RESULTS: The inhibitory rate of NS-398 combined with BOR was higher than that of
      NS-398 or BOR alone(Q>0.85). After treatment of NS-398 combined with BOR, the
      percentage of cells arrested in the G0/G1 phase and apoptotic rate were both
      higher than that of treatment with each drug alone(Q>1.15). The caspase-3
      activity in cells treated with combined of NS-398 and BOR was significantly
      higher than that of treatment of each drug alone(Q>1.15). CONCLUSION: NS-398
      combined with BOR shows a synergistic effect on the growth inhibition of RPMI
      8226 cells in vitro.

PMID- 29070120
TI  - [Expression of DNMT3b Gene in Myeloma RPMI 8226 Cells and Its Biological
      Significance].
AB  - OBJECTIVE: To study the expression of DNMT3b gene in myeloma RPMI8226 cells and
      its biological significance. METHODS: The activity of DNA methyltransferase was
      detected by ELISA, and the expression of DNMT3b in RPMI8226 cells was analyzed by
      semi-quantitative RT-PCR and real-time fluorescent quantitative PCR. The
      proliferation and expression of DNMT3b gene in RPMI8226 cells intervened with
      capecitabine for 24 hours were detected. RESULTS: The activity of DNMT and
      expression of DNMT3b in RPMI 8226 cells increased. The proliferation of RPMI8226
      cells was inhibited, and the apoptosis occurred in RPMI 8226 cells intervened
      with capecitabine for 24 hours. The expression level of DNMT3b gene was decreased
      after being intervened with capecitabine for 24 hours. CONCLUSION: The expression
      level of DNMT3b in myeloma RPMI 8226 cells increase, and capecitabine can inhibit
      the proliferation of RPMI 8226 and induce apoptosis by inhibiting the expression
      of DNMT3b gene. Therefore, DNMT3b is expected to be a new target for myeloma
      therapy.

PMID- 29070121
TI  - [Survival and Prognosis Analysis of 57 Patients with Multiple Myeloma].
AB  - OBJECTIVE: To investigate the relationship of clinical related indicator levels
      and clinical staging with the prognosis of MM patients so as to more accurately
      evaluate the disease status and guide the clinical treatment. METHOD: The
      clinical indicators including age, WBC and Plt counts, FISH result, ISS staging,
      Kappa and Lammada light chain levels and so on in 57 cases of MM were analyzed
      retrospectively; the unvariate and multivatiate analyses of factors influencing
      the prognosis of MM patients were performed by Kaplan-Meier and Cox regression
      model; the factors influencing the prognosis of patients were evaluated. RESULTS:
      Median age of 57 patients including 25 male and 32 female, was 63(29-81) years
      old, mean OS time was 37.3 months, mean PFS time was 36.3 months, 3-year OS and
      PFS were 73.6% and 56.1% respectively. The unvaviate analysis showed that age,
      WBC count, Plt count, FISH result, ISS staging, Kappa and lammda light chain
      levels, and remission were factors influencing the prognosis; the multivatiate
      analysis showed that the Kappa light chain level >=19.4 mg/L and Plt count
      <100*109/L were independant risk factors influencing the prognosis of MM
      patients. CONCLUSION: The prognosis of MM patients with high Kappa light chian
      level and low Plt count is very poor, therefore the therapeutic regimens should
      be selected differentially for this kind of newly diagnosed MM patients so as to
      enhance the survival time of patients.

PMID- 29070122
TI  - [Levels of T-Lymphocyte Subsets, IL-17, IL-35 and IFN-gamma in Peripheral Blood
      and Their Clinical Significance in Patients with Multiple Myeloma].
AB  - OBJECTIVE: To explore the levels of T-lymphocyte subsets and IL-17, IL-35, IFN
      gamma in peripheral blood of patients with multiple myeloma(MM) and their
      clinical significance. METHODS: A total of 86 MM patients in our hospital from
      January 2014 to January 2017 were enrolled in MM group and 30 healthy persons
      were enrolled in control group, the CD4+/CD8+ T cells ratio, CD4+CD25high/+
      CD127low/- Treg level in peripheral blood were detected by flow cytometer. The
      levels of IL-17, IL-35 and IFN-gamma in peripheral serum were detected by ELISA,
      and the differences of detected indicators between different groups were
      compared. RESULTS: Compared with control group, the proportion of CD4+ T cells
      and CD4+/CD8+ T cells ratio decreased, the proportion of CD8+ T cells and Treg
      increased in MM group. The differences of T lymphocyte subsets level between
      group III stage of MM and control group were statistically significant (P<0.05).
      With enhancing of clinical stages, Treg level showed a increasing trend,
      especially in III stage (P<0.05), the serum level of IL-17 as followed in turn:
      III stage>II stage>I stage>control, the serum level of IL-35 and IFN-gamma as
      followed in turn: control>I stage>II stage>III stage (P<0.05). In terms of
      disease status, the propurtion of Treg cells as fllowed in turn: disease
      progression stage>stable stage>control (P<0.05), the serum level of IL-17 as
      followed in turn also: disease progression stage>stable stage (P<0.05), while the
      serum level of IL-35 and IFN-gamma as followed in turn: control>disease table
      stage>progression stage (P<0.05). CONCLUSION: The abnomal level of T-lymphocyte
      subsets, Treg, IL-17, IL-35 and IFN-gamma are related with progression and
      prognosis of MM patients.

PMID- 29070124
TI  - [Analysis of Relationship between Serum Total Light Chain kappa/lambda Ratio and
      Proportion of Bone Marrow Plasma Cells in Patients with IgG type and IgA type
      Multiple Myeloma].
AB  - OBJECTIVE: To explore the relationship between serum total light chain
      kappa/lambda ratio (sTLC-kappa/lambda) and proportion of bone marrow plasma cells
      (BMPC) in patients with IgG type and IgA type multiple myeloma (MM) and its
      clinical significance. METHODS: The levels of serum IgG, IgA, kappa type and
      lambda type total light chain were detected in 79 newly diagnosed patients with
      IgG type (n=52) and IgA type (n=27) MM by immuno-nephelometric assay and the sTLC
      kappa/lambda ratio was calculated. The proportion of BMPC was determined by bone
      marrow smears in the corresponding period, and the changes in sTLC-kappa/lambda
      ratio and the proportion of BMPC were observed in 19 patients with IgG type(n=16)
      and IgA type (n=3) MM undergoing treatment, 26 cases of non-phasmocytic
      proliferative diseases were enrolled in control group. RESULTS: In MM patients
      with IgGkappa type and IgAkappa type, the sTLC-kappa/lambda ratio was
      significantly higher than that in the control group (P<0.01), while in MM
      patients with IgGlambda type and IgAlambda type, the sTLC-kappa/lambda ratio was
      significantly lower than that in the control group (P<0.01). In MM patients with
      IgGkappa, the sTLC-kappa/lambda ratio was significantly higher than that in MM
      patients with IgAkappa(P<0.01), while the sTLC-kappa/lambda ratio in MM patients
      with IgGlambda was significantly lower than that in MM patients with IgAlambda.
      The sTLC-kappa/lambda ratios in MM patients with IgGkappa and IgAkappa were
      positively correlated with the concentrations of IgG (r=0.778,P=0.000) and IgA
      (r=0.601,P=0.039), while the sTLC-kappa/lambda ratios of patients with IgGlambda
      and IgAlambda were negativily correlated with the IgG(r=-0.586,P=0.01) and IgA
      level(r=-0.718,P=0.003). In addition, a correlation between each type MM was not
      found except the IgGkappa type MM which had a positive correlation between the
      sTLC-kappa/lambda ratio and proportion of BMPC (r=0.579,P=0.002). Nonetheless, 18
      of 19 patients with IgG type and IgA type MM undergoing treatment showed
      concordance between the sTLC-kappa/lambda ratio and proportion of BMPC change.
      CONCLUSION: There is a lower correlation between the sTLC-kappa/lambda ratio and
      the proportion of BMPC in MM patients with IgG type and IgA type, but there is a
      high concordance between the sTLC-kappa/lambda ratio and the proportion of BMPC
      change in the same patient and it suggests that the sTLC-kappa/lambda ratio plays
      an important role in the diagnosis and monitoring of IgG type and IgA type MM.

PMID- 29070123
TI  - [Effect of B Lymphocyte-Induced Mature Protein-1 Expression in Bone Marrow
      Mononuclear Cells on Prognosis of Patients with Multiple Myeloma].
AB  - OBJECTIVE: To study the effect of B lymphocyte-induced mature protein-1(Blimp1)
      expression in bone marrow mononuclear cells on the prognosis of patients with
      multiple myeloma. METHODS: Forty-eight patients with multiple myeloma from
      January 2014 to January 2015 were selected. The expression of Blimp1 in the bone
      marrow of all the patients was measured. According to the median score of Blimp1
      expression level, the patients was divided into low expression group (L group, 22
      cases) and high expression group (H group, 26 cases). The related influencing
      factors of different Blimp1 expression levels, the clinical efficacy,
      immunophenotypic changes and progression-free survival(PFS) were compared between
      different Blimp1 expression groups. RESULTS: There were no significant
      differences in sex, age, type, stage and treatment stage between the 2 groups (P>
      0.05). The total remission rate of the low expression group was significantly
      higher than that in the high expression group (P<0.05). However before treatment,
      there was no significant difference in the positive rate of CD19, CD38, CD56,
      CD138 and minimal lesion between the 2 groups (P> 0.05); after treatment the
      positive expression rates of CD38, CD56, CD138 and minimal lesion in the low
      expression group were significantly lower than those in the high expression
      group. While the positive expression rate of CD19 was significantly higher than
      that in high expression group (P<0.05). The PFS of 1, 2 and 3 years in the low
      expression group was significantly higher than that in the high expression group
      (P<0.05). CONCLUSION: The MM patients with the high in staging and the larger in
      diffeculty of treatment possess high Blimp1 expression, however, the therapeutic
      efficacy and prognosis of MM patients with low Blimp1 expression are
      significantly better than those of MM patients with high Blimp1 expression.

PMID- 29070125
TI  - [Effects of Recombinant Human Erythropoietin on MPC-11 Myeloma Cells Cultured In
      Vitro].
AB  - OBJECTIVE: To explore the effect of recombinant human erythropoietin (rhEPO) on
      myeloma cell line MPC-11 in vitro and its anti-tumor mechamism so as to provide
      the theoretic evidence for treatment of multiple myeloma by using rhEPO. METHODS:
      MPC-11 cells were cultured in RPMI 1640 medium, then the MPC-11 cells in
      logarithmic growth phase were seed in 96 well culture plates at a density of
      1*104/ml cells with 100 ul per well. For all the experiments, the control and
      rhEPO groups were set up, and the rhEPO group was divided into different
      concentration groups: 20, 40, 60, 80, 100, 200 and 400 rhEPO U/ml. The cultured
      MPC-11 cells in each groups were collected at day 1, 2, 3, 4, 5 and 6, and the
      viability of MPC-11 cells was assayed by using CCK-8 method, the MPC-11 cell
      apoptosis was detected by flow cytometry with Annexin V/PI double staining, the
      levels of IL-6, IgG and kappa light chain in cell supernatant were detected by
      ILISA. RESULTS: The apoptosis rate in MPC-11 cells treated with 200 U/ml of rhEPO
      at day 21 was significantly higher than that in control group(P<0.05); the
      apoptosis rate in MPC-11 cells treated with 400 U/ml of rhEPO at day 10, 15, 21
      was higher than that in control group at same time points, respectively (P<0.05),
      suggesting that the MPC-11 cell apoptosis rate was enhanced with increase of
      rhEPO concentration and prolonging of culture time(P<0.05), the IL-6 level in
      supernatant of cell treated with 400 U/ml of rhEOP for 15 days was lower than
      that in control group(P<0.05), while the IL-6 level in supernatant of cells
      treated with 100, 200, 400 U/ml of rhEPO for 21 days decreased (P<0.05); The
      levels of IgG and kappa light chain in supernatant of cells treated with 400 U/ml
      of rhEPO for 21 days all were significantly lower than those in control
      group(P<0.05). CONCLUSION: The rhEPO can induce apoptosis of MPC-11 cells with
      concentration- and time-dependent manner, and can reduce levels of IgG, kappa
      light chain secreted by MPC-11 cells with time-dependent manner.

PMID- 29070126
TI  - [Screening of Serum Peptidome-Based Biomarker for Multiple Myeloma Renal
      Impairment].
AB  - OBJECTIVE: To screen serum peptide associated with renal impairment in patients
      with multiple myeloma(MM) and search early biomarker of MM renal impairment.
      METHODS: The weak cation exchange magnetic bead combined with matrix assisted
      laser desorption/ionization time of flight mass spectrometry was used to compare
      and analyze serum peptidome of MM with or without renal impairment. RESULTS:
      There were 18 peptide peaks with statistical significance in the molecular weight
      range from 700 to 10 000 Da(P<0.05), among them 7 peptides were upregulated and
      11 were downregulated. The Quick Classifier diagnostic model composed of 3
      peptides, which can strongly distinguish MM patients with or without renal
      impairment by means of Embedded Software. Its sensitivity and specificity were
      97.14% and 94.12%, respectively. Peptides with molecular weight of 3908.85 Da and
      3216.06 Da were significantly upregulated in MM patients with renal impairment,
      while the peptide with molecular weight of 2990.08 Da was significantly
      downregulated in MM patients with renal impairment. CONCLUSION: Peptides
      associated with MM renal impairment obtained by serum peptidome technology can
      provide a new clue for early assessment and diagnosis of clinical MM renal
      impairment.

PMID- 29070127
TI  - [Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its
      Mechanism].
AB  - OBJECTIVE: To investigate the inhibitory effect of decitabine (DAC) in various
      dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism.
      METHODS: LC-MS/MS method was used to test the blood DAC concentration of 2 groups
      of MDS patients being treated with DAC 20 and 15 mg/m2*5 d. In according to the
      various blood DAC concentration levels, the MDS-L cells were treated with
      different DAC dosages for 24, 48, 72 and 96 h, respectively. The CCK-8 method was
      applied to determine the cell proliferation, the flow cytometry was used to
      analyze the cell cycle and cell apoptosis changes, the P15INK4B DNA methylation
      status was measured by methylation specific PCR using EZ DNA Methylation-Gold
      Kit. RESULTS: The blood DAC concentration of MDS patients treated with DAC 20
      mg/m2*5 d was 174.08+/-80.15(84.7-311) ng/ml, which was significantly higher than
      89.87+/-32.94(43.2-165)ng/ml for the group treated with 15 mg/m2*5 d (P=0.014).
      DAC could notably inhibit the proliferation of MDS-L cells, and the effect was in
      dose- and- time-dependent manner(r=0.786). However, when DAC concentration was
      >=0.1 ug/ml, the proliferation inhibition rates were not significantly different
      between various dosages. After DAC treatment, MDS-L cells in G1 phase increased
      notably, while cells in S phase decreased significantly. Also, the P15INK4B DNA
      methylation status of MDS-L cells decreased after being treated with DAC for 96
      h, but the difference was not significant between various dosages. CONCLUSION:
      DAC can significantly suppress MDS-L cell proliferation, block MDS-L cells in G1
      phase and induce the apoptosis at low concentration (0.1-0.2 ug/ml).

PMID- 29070128
TI  - [Clinical Observation of Therapeutic Regimen Consisted of Decitabine Combined
      with Low-Dose IA Regimen for Myelodysplastic Syndrome-EB].
AB  - OBJECTIVE: To investigate the clinical efficacy of decitabine combined with low
      dose IA for treating patients with myelodysplastic syndrome-EB. METHODS: Thirty
      seven cases of myelodysplastic syndrome-EB patients diagnosed in the First
      Affiliated Hospital of Xi'an Jiaotong University from June 2015 to January 2017
      were analyzed retrospectively. These patients accepted DAC+IA(19 cases) and
      DAC(18 cases) treatment separately, and the differences of clinical efficacy
      between them were compared. RESULTS: After 1-2 treatment cycles, in DAC+IA group
      the rate of complete remission with full hematologic recovery and incomplete
      hematologic recovery was 57.9%, and overall response rate was 100%. Immature
      cells level observed in bone marrow pathology was significantly decreased,
      compared with level before treatment. Peripheral blood neutrophil count,
      hemoglobin level and platelet count increased significantly. The median duration
      of the complete remission was 7.3 months. The progression free survival time was
      10 months. Three patients with complete remission relapsed after interruption of
      treatment for 3.5 months. In DAC group complete remission rate was 16.7%, and
      overall response rate was 38.9%. The progression free survival lasted for 6
      months. The median time of 3 complete remission patients transformed to AML was 4
      months. The common adverse reactions were myelosuppression and infection without
      significant difference between the 2 groups. CONCLUSION: The regimen of
      decitabine combinated with low-dose IA for treating patients with myelodysplastic
      syndrome-EB is effective, which can prolong the survival and improve the quality
      of life, whereas the long-term effect needs to be consolidated by allogeneic
      hematopoietic stem cell transplantation.

PMID- 29070129
TI  - [Clinical Efficacy of Low-dose Decitabine Combined with CAG Regimen in Patients
      with Myelodysplastic Syndrome-refractory Anemia with Excess Blasts(MDS-RAEB)].
AB  - OBJECTIVE: To investigate the clinical efficacy of low-dose decitabine combined
      with CAG regimen in patients with myelodysplastic syndrome-refractory anemia with
      excess blasts (MDS-RAEB) through retrospective analysis. METHODS: Thirty-six
      patients with MDS-RAEB who ever received low-dose decitabine combined with CAG
      regimen were enrolled into decitabine + CAG group and 40 patients with MDS-RAEB
      treated by decitabine alone in our center were enolled into the control group.
      The clinical characteristics, efficacy and adverse reactions (AE) were compared
      between the 2 groups. RESULTS: Compared with the control group, the overall
      response rate (ORR) [complete remission (CR)+partial remission (PR) + hematologic
      improvement (HI) rate] of the decitabine+CAG group was higher (83.3% vs
      62.5%)(P=0.043), and the AEs were not significantly increased. Cytopenia grade
      >=3 and infection after treatment were the most prevalent AEs, which occurred in
      the early stage (within the first 2 cycles) and gradually decreased later. Other
      non-hematologic AEs were infrequent. CONCLUSION: Low-dose decitabine combined
      with CAG regimen has better clinical efficacy for patients with MDS-RAEB than
      that of decitabine alone. It is worthy to be applied in clinic, especially for
      these patients who are not ineligible for hematopoietic stem cell
      transplantation.

PMID- 29070130
TI  - [Establishment of A Myelodysplastic Syndrome Transformed to Leukemia Cell Line
      Stably Expressing Green Fluorescent Protein].
AB  - OBJECTIVE: To establish a myelodysplastic syndrome transformed to leukemia cell
      line stably expressing green fluorescent protein (GFP), and to evaluate its
      biological characteristics and applications. METHODS: SKM-1 cells were
      transfected by lentiviral particles with vector of GFP. The GFP positive single
      cell clone was isolated by limiting dilution and continued being cultured. The
      cells were injected into mice subcutaneously and were screened in vivo. Then SKM
      1/GFP cells were obtained after tumour plaque was separated and cultivated. The
      cell morphology was observed by fluorescence microscopy. The GFP expression was
      further detected by flow cytometry. The cell proliferation was analysed by CCK-8
      assay. SKM-1/GFP cells were inoculated to subcutaneous tissue of the
      immunodeficiency mice. The growth and invasion of the tumour were observed after
      tumour formation. RESULTS: No differences in cell morphology and growth
      characteristics were observed between SKM-1 cells and SKM-1/GFP cells. The rate
      of GFP expression was 100%. No differences in cell proliferation were observed
      between SKM-1 cells and SKM-1/GFP cells. The tumour mass was observed after 14
      days of subcutaneous vaccination in NOD/SCID mice. Spontaneous fluorescence from
      plaque was observed by living fluorescence microscopy at 30th day after
      vaccination. Homogenous GFP positive cells were observed by fluorescence
      microscopy in the frozen section of tumour mass. The invasion of SKM-1/GFP cells
      was also detected in heart, liver, stomach and kidney of mice. CONCLUSION: A
      myelody-splastic syndrome transformed to leukemia cell line stably expressing
      green fluorescent protein has been established successfully, which can track
      tumor cell sensitively and can be applied to the research of minimal residual
      leukemia. The establishment of SKM-1/GFP cells may serve as a powerful means for
      studing myelodysplastic syndrome transformation.

PMID- 29070131
TI  - [Efficacy of Shengxue Mixture Combined with Intraosseous Infusion for Treatment
      of Aplastic Anemia].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Shengxue mixture combined with
      intraosseous blood infusion for treatment of aplastic anemia patients. METHODS:
      From 2011 to 2015, Institute of blood diseases of Shaanxi Medical University
      admitted 53 patients with aplastic anemia. The patients were treated with
      shengxue mixture 200 ml, orally, twice a day. Stanozolol tablets, Adult 2 mg,
      three times a day, mycophenolate mofetil 1.0 g, twice a day. Intraosseous
      infusion of the following medicine were administered in patients: recombinant
      human EPO 10000 U, recombinant human G-CSF 450 ug, recombinant human IL-11 4.5
      mg, dexmethasone 20 mg, once a week, a total of four times. One month later, the
      blood cell counts and bone marrow biopsy were performed. Consolidation treatment
      continued for 3 to 6 months after discharge, and therapeutic effect was observed
      and followed-up for more than a year. RESULTS: After one month of treatment, 40
      patients were basically cured (75.47%), 8 patients were remitted(15.09%),
      Hemoglobin level, white blood cell count and platelet count were significantly
      improved after treatment (P<0.01). The overall response rate was 90.57%(48
      patients). Patients with bone marrow hyperplasia was 46 (86.79%), versus
      9(16.98%) before treatment. There was a difference (P<0.05). After 3 to 6 months
      of treatment, 40 patients were cured (75.47%); 8 patients were remitted(15.09%);
      3 patients were obviously improved(5.66%); 2 patients were ineffective(3.77%).
      The overall response rate was 96.23%(51 cases). No obvious side effects were
      observed. No patients were relapsed after one year. CONCLUSION: Shengxue mixture
      combined with Intraosseous infusion is a fast, efficient, safe method for the
      treatment of aplastic anemia.

PMID- 29070132
TI  - [A Systematic Review of the Value of Thrombelastography or Thromboelastometry for
      Prediction of Venous Thromboembolism].
AB  - OBJECTIVE: To systematically collect the thrombelastography (TEG)-or
      thromboelastometry (ROTEM)-related data, and predict to evaluate their values for
      the prediction of thromboembolic events. METHODS: Databases including PubMed,
      Central and Embase were searched for the related clinical trials, and the
      references were retrieved manually; these included references were assessed
      qualitatively by the QUADAS-2 tool; finally the enrolled researches were
      qualitatively analyzed. RESULTS: A total of 15 studies consisting of 293 VTE
      patients met the inclusion criteria. The overall quality and the accuracy of TEG
      or ROTEM in predicting VTE varied a lot. Two thirds of the studies displayed that
      the changes of TEG parameters or ROTEM were related to the occurrence of VTE.
      CONCLUSION: The present studies showed that the TEG or ROTEM for predicting the
      VTE display higher difference in accuracy, therefore, the combination of TEG or
      ROTEM with other laboratory tests may improve the accuracy of VTE diagnosis.

PMID- 29070133
TI  - [Main Factors Influencing FeCl3-Induced Mouse Mesenteric Arteriole Thrombosis
      Model].
AB  - OBJECTIVE: To investigate the factors that influence FeCl3-induced mouse
      mesenteric arteriole thrombosis model. METHODS: Platelets were isolated from
      donor mice and labeled with Calcein-AM. Mice were transfused intravenously with
      Calcein-AM labeled platelets. The influence of mouse ages (3-6 weeks, 6-10 weeks
      and >10 weeks), transfused platelets counts (1*107, 1*108 and 2*108 platelets)
      and concentrations of FeCl3 (6%, 12%, 24% and 48%) on FeCl3-induced thrombosis
      model were compared. RESULTS: The occlusion time was 16 min for mice aged 3-6
      weeks, which was shorter than that for 6 mice aged 6-10 weeks(25 min)(P<0.05) and
      that for mice aged >10 weeks(38 min)(P<0.01). The occlusion time resulting from
      transfusion of 1*108 and 2*108 of pletclets was 15-18 min, which was shorter than
      that of transfusion 1*107 platelets (30 mins). The occlusion time resulting from
      transfusion of 6% and 12% FeCl3 was from 15 to 20 min, however the transfusion of
      24% and 48% FeCl3 all in all leads to vessel occlusion within 10 min. CONCLUSION:
      The factors influencing the success of FeCl3-induced mouse thrombosis model are
      more. Transfusion of 1*108 to 2*108 labeled platelets to 3-6 week-old mice, and
      6% to 12% of FeCl3 should be used to induce thrombosis, and the experimental
      conditions should be optimized for this animal model, therefore, it is easier for
      us to set up a mouse mesenteric arteriole thrombosis model.

PMID- 29070134
TI  - [Comparison of Therapeutic Efficacy of Anticoagulation and Its Combination with
      Catheter-directed Thrombolysis for Deep Venous Thrombosis of Lower Extremities].
AB  - OBJECTIVE: To investigate the therapeutic efficacy of anticoagulation(AC) and its
      combination with catheter-directed thrombolysis(CDT) for deep venous thrombosis
      of lower extremities. METHODS: One hundred and thirty-nine patients with deep
      venous thrombosis of early lower extremities treated in our hospital from May
      2011 to September 2013 were selected and randomly divided into the AC group(n=
      66) and CDT+AC group(n= 73). The thrombolytic effects, adverse reactions, post
      thrombotic syndrome (PTS) and quality of life were evaluated. RESULTS: There were
      no serious adverse events during treatment and after treatment in the 2 groups.
      Hematomas in 2 cases and gross hematuria in 3 cases were observed in the CDT+AC
      group. The gums bleed or gross hematuria in 3 cases were observed in the AC
      group. Compared with the AC group, the number of grade I thrombolysis in CDT+AC
      group decreased significantly (60.61% vs 9.59%)(P< 0.05), and the number of grade
      III thrombolysis increased significantly(7.57% vs 49.31%)(P< 0.05). During follow
      up, the incidence of PTS in both groups showed increase year by year, and none of
      the patients had severe PTS. The incidence PTS in CDT+AC group at 12 months and
      18 months were lower than those of AC group(17.81% vs 33.33%, 24.66% vs
      43.94%)(P< 0.05). Compared with the AC group, the scores of physiological role
      and vitality in CDT+AC group at 6 months, 12 months and 18 months were higher (P<
      0.05). CONCLUSION: Catheter-directed thrombolysis combined with AC therapy can
      promote the mitigation of clinical symptoms in patients with DVT of lower
      extremities and is beneficial to promoting the life quality of patients.

PMID- 29070135
TI  - [Genetic Analysis of A Case of Congenital Dysfibrinogenemia Caused by Arg16His
      Mutation in Exon 2 of FGA].
AB  - OBJECTIVE: To analyze the phenotype and genotype of a family with congenital
      dysfibrinogenemia. METHODS: Assays of coagulation, including activated partial
      thromboplastin time(APTT), pro-thrombin time(PT)and thrombin time(TT) were
      carried out with Sysmex CA-7000 in the proband and his family members. The
      quality and quantity of fibrinogen in plasma were determined by Clauss and
      electrophoresis, respectively. Fibrinogen and inconstituent were analyzed by
      Native-PAGE. All exon and exon intron boundaries of fibringen genes were analyzed
      by direct sequencing. RESULTS: The proband had normal APTT, but prolonged PT and
      TT. The activity of fibrinogen in plasma was decreased while its quantity was
      normal. These abnormalities were also found in his sisters and daughter, while
      his wife was normal. Genetic analysis revealed heterozygous G1233A in the exon 2
      of FGA which resulted in Arg16His missense mutation. CONCLUSION: Inherited
      dysfibrinogenemia is caused by Arg16His mutation in exon 2 of FGA.

PMID- 29070136
TI  - [Analysis of Hematopoietic Reconstitution in Auto-Peripheral Blood Hematopoietic
      Stem Cell Transplantation].
AB  - OBJECTIVE: To explore the factors which may have influences on hematopoietic
      reconstitution of the auto-peripheral blood stem cell transplantation(auto
      PBHSCT). METHODS: The successful rate, the time of hematopoietic reconstitution
      and implantation status at 28 days after transplantation of 177 patients received
      auto-PBSCT were retropectively analyzed, in order to explore the factors which
      may have influences on hematopoietic reconstitution. RESULTS: The median time of
      neutrophil recovery was 12 days (8-21 days), implantation rate was 98.9%, all
      patients' neutrophil were recovered in 28 days. The median time of platelet
      recovery was 17 days (7-420 days), implantation rate was 95.5%, the cumulative
      incidence of platelet recovery at day 28 was 80.8%. Univariate analysis showed
      that the CD34+ cell number and the use of TPO had effect on neutrophils recovery
      time; the disease kinds, conditioning regimen and the infused CD34+ cell number
      had influence on platelets recovery time. Multivariate analysis showed that the
      CD34+ cell number was the independent influencing factor of neutrophils
      reconstitution time; the disease kinds, the CD34+ cell number were the
      independent influencing factors of platelet reconstitution time. Disease kinds
      and the CD34+ cell number were the independent influencing factors of
      hematopoietic reconstitution status of 28 days after transplantation. CONCLUSION:
      In auto-PBHSCT patients, disease kinds, conditioning regimen, the infused CD34+
      cell number and the use of TPO have been confirmed to be independent influencing
      factors on hematopoietic reconstitution.

PMID- 29070138
TI  - [Identification of a Rare Ael05/B101 Subtype and Selection of Blood Transfusion
      Strategy].
AB  - OBJECTIVE: To explore the mechanism of ABO discrepancy in a patient by ABO
      genotyping and the reasonable blood transfusion strategy. METHODS: Routine
      serological test was carried out to analyze ABO blood group. The presence of the
      blood group determinants on the red blood cells were determined by adsorption
      elution test. Exons 1-7 and adjacent introns of the ABO gene were amplified by
      PCR and sequenced. RESULTS: The patient showed ABO forward and reverse typing
      discrepancy. ABO forward typing defined as B, however, the reverse typing
      indicated that the patient was AB subtype. Absorption-elution test confirmed weak
      A antigens on the patient's red blood cells. The ABO gene sequencing showed a T>C
      exchange at position in exon 7 which resulted in a isoleucine to threonine
      substitution at codon 256. The ABO blood group genotype was ABO*Ael05/B101.
      CONCLUSION: The 767 T>C substitution in the gene of alpha-1,3-N-acetyl galactose
      is the molecular mechanism leading to the decrease expression of A antigen of the
      Ael05 subtype.

PMID- 29070137
TI  - [Clinical Study on Treatment of Juvenile Myelomonocytic Leukemia with
      Haploidentical-Hematopoietic Stem Cell Transplantation].
AB  - OBJECTIVE: To analyze the therapeutic efficacy of haploidentical-hematopoietic
      stem cell transplantation (hi-HSCT) for patients with juvenile myelomonocytic
      leukemia (JMML). METHODS: The engraftment of hematopoietic stem cells, incidence
      of graft versus host disease (GVHD), infection, relapse, and survival of 6 JMML
      patients received hi-HSCT were retrospectively analyzed. RESULTS: Six (6 males)
      JMML patients received hi-HSCT from haplo-HLA-matched related donors. The results
      showed that the hematopoictic stem cells in all 6 patients were grafted
      successfully. Two cases of JMML died of pulmenary infections, other 4 cases
      survive without disease. Acute GVHD occurred in 3 patients and chronic GVHD
      occurred in 1 patients. The overall survival, disease free survival and relapse
      rates were 66.7%, 66.7%, 0%, respectively. CONCLUSION: The hi-HSCT is an
      effective method for treatment of patients with JMML, but there also is a serial
      problems to be resolved.

PMID- 29070139
TI  - [Analysis of Correlation between IgG Titer of Pregnant Women and Neonatal
      Hemolytic Complications of Different Blood Groups].
AB  - OBJECTIVE: To study the relationship between IgG titer of pregnant women and
      hemolytic disease of newborn(HDN) with different blood groups. METHODS: Four
      hundred pregnant women, including pregnant women with type O blood, were selected
      from May 2014 to January 2015 in our hospital for inspection and a couple of
      different blood groups, the IgG titer of pregnant women were detected in the
      inspection process. According to neonatal HDN, newborns were divided into 2
      groups: HDN group(85 cases) and non-HDN group(315 cases). The incidence of
      postpartum neonatal hemolytic disease was tracked and the correlation of IgG
      titers with HDN were systematically analyzed. RESULTS: In the production and
      inspection process, the IgG titer in pregnant women was divided into <1:64, 1:64,
      1:128, 1:256 and greater than or equal to 1:512 five groups. the comparison of
      HDN incidence rate in 4 groups of IgG titer >64 and IgG titer <1:64 group showed
      that the prevalence of ABO hemolytic disease of newborn were 96.9%, 79.6%, 63, 7%
      and 28.8%, there was a certain correlation of pregnant women IgG titers with ABO
      hemolytic disease of the newborn, that is, with the increase of IgG titer, the
      incidence of hemolytic disease of newborns increased in certain degree
      (r=0.8832), the risk in 4 groups of neonatal HDN was higher than that in IgG
      titer <1:64 of IgG titer >64 HDN group. CONCLUSION: There is a certain corelation
      between prevalence of ABO-HDN and IgG titer of pregnant women. For these pregnant
      women, the control of the pregnant women IgG titer has a positive clinical
      significance to reduce the incidence of hemolytic disease of the newborn.

PMID- 29070140
TI  - [ZNF300 Promotes Megakaryocytic Differentiation].
AB  - OBJECTIVE: To study the function of ZNF300 in the megakaryocytes differentiation
      and proliferation. METHODS: Public data analysis of ZNF300 expression and
      megakaryocyte culture were used to reveal the correlation of ZNF300 expression
      with leukemia and megakaryocyte differetniation; ZNF300 overexpression was
      mediated by lentiviral or retroviral infection, and the differentiation and
      proliferation of K562 cells and primary mouse bone marrow cells to magekaryocytes
      were measured by flow cytometry, MTT assay and colony-forming test; the ZNF300
      subcellular localization was tested by separating cytosolic and nuclear extracts
      combined with Western blotting. The dual-luciferase assay and ChIP-qPCR were used
      to study ZNF300 target gene. RESULTS: ZNF300 expression upregulation correlated
      with megakaryoyte differentiation; over-expression of ZNF300 promoted CD41 and
      CD61 expression, inhibited cell cycle progress, and could reduce colony-forming
      unit. The ZNF300 locolized in nuclear and regulated C-MYC expression. CONCLUSION:
      ZNF300 promotes megakaryocyte differentiation.

PMID- 29070141
TI  - [Therapeutic Effect of Recombinant Human Stem Cell Factor on Rhesus Monkeys with
      Severe Acute Radiation Sickness].
AB  - OBJECTIVE: To study the therapeutic effect of rhSCF early administration on
      rhesus monkeys with severe acute radiation sickness(ARS). METHODS: Twelve adult
      monkeys totally exposed to 7.0 Gy 60Co were divided into radiation control and
      SCF groups, and monkeys in SCF group were subcutaneously injected recombinant
      human SCF(rhSCF) 200 ug/kg at half an hour and 24 hour after irradiation, while
      the radiation control monkeys were injected physiological saline. Survival was
      monitored and hematopoiesis was evaluated at 40 days following early treatment.
      RESULTS: 6 animals treated with rhSCF all survived, while 2 in irradiated
      controls survived on 40 day after radiation. rhSCF treatment promoted
      hematopoiesis recovery significantly, increased the nadir of white blood cells,
      neutrophils and platelets, and simplified supportive care in ARS rhesus monkeys.
      CONCLUSION: RhSCF injection soon after TBI taken shows an significant therapeutic
      efficiency on rhesus monkeys with severe acute radiation sickness.

PMID- 29070142
TI  - [Effect of BBG on Acute Graft-Versus-Host Disease in Mice after Allogeneic
      Hematopoietic Stem Cell Transplantation].
AB  - OBJECTIVE: To investigate the effect of P2X7R antagonist brilliant blue G (BBG)
      on aGVDH of mice after allo-HSCT. METHODS: aGVHD mouse model after HSCT was
      established and treated with the P2X7R antagonist BBG of different dosages (50
      mg/kg and 75 mg/kg). After treatment, the survival, body weight, pathological and
      liver function of aGVDH mice were abserved, and the expression levels of P2X7,
      NLRP3, caspase-1, IL-1beta, IL-18 mRNA and protein were evaluated by real-time
      PCR and Western blot. RESULTS: The allo-HSCT aGVHD mouse model was successfully
      established, the intraperitoneal injection of BBG alleviated the aGVHD clinical
      manifestations including roachback, ruffled fur, skin peeling and weight loss of
      recipient mice, decreased P2X7R and IL-1beta expression and reduced the mRNA
      levels of P2X7R, NLRP3, Caspase-1, IL-1beta and IL-18. Furthermore, GVHD group
      receiving 75 mg/kg BBG showed most significant difference of these indexes.
      CONCLUSION: BBG alleviates liver inflammatory damage induced by aGVHD after allo
      HSCT, and decreases the expression of proinflammatory cytokines. Moreover, the
      protective effect of that of BBG 75 mg/kg group is better than that of BBG 50
      mg/kg group.

PMID- 29070143
TI  - [Differential Regulation of Bruton's Tyrosine Kinase by the Ubiquitin Pathway].
AB  - OBJECTIVE: To investigate the regulation of Bruton's tyrosine kinase (Btk) and to
      explore its possible mechanism. METHODS: After treatment with the proteasome
      inhibitors and/or phorbol esters (PMA), the mRNA and protein expression level of
      Btk was detected by RT-PCR and Western blot, respectively. The ubiquitination
      level of Btk in B lymphoblastoid A20 cells was estimated after stimulation via
      the crosslinking of BCR with anti-IgM antibody. The cotransfection of COS-7 cell
      with Btk, ubiquitin and Cbl was performed, then the ubiquitination level of Btk
      was measured. The Btk ubiquitination level was detected after ectopic expression
      of ubiquitin transfected with the wild type or triple mutant of Ub (K29R, K48R,
      K63R) . Mono-ubiquitination of Btk was detected with antibodies preferentially
      against monovalent ubiquitin; in addition, the protein expression levels of
      chloroquine-treated stably transfected cells expressing Btk-GFP were detected by
      Western blot, and quantified with the strength of GFP fluorescence. RESULTS: In
      the presence of proteasome-specific inhibitors and/or PMA, steady-state levels of
      Btk protein were reduced due to decrease of transcription. Posttranslational
      modification of Btk by ubiquitination was observed, which was related with the
      level of Btk expression and activation. The E3 ubiquitin ligase Cbl, which binds
      to Btk, was also found to ubiquitinate this kinase. Altogether, the data of this
      study strongly suggest that Btk is regulated by poly- and/or mono-ubiquitination
      events. CONCLUSION: The Btk protein is dictated by its expression level through
      the ubiquitination pathway.

PMID- 29070144
TI  - [Evaluation of nCD64 and CD14 Index as Diagnostic Markers for Hematologic Tumors
      Combined with Bacterial Infection].
AB  - OBJECTIVE: To explore the value of both CD64(nCD64 IND) and CD14 (CD14 IND) Index
      of peripheral blood neutrophils as the diagnostic markers of hematologic tumors
      combined with bacterial infection. METHODS: Sixty-four patients with
      hematological tumors were selected and divided into the group complicated with
      bacterial infection (infection group, 33 cases) and the non-infection group (31
      cases), the flow cytometry was be used to detect the related peripheral blood
      markers CD64 and CD14, the nCD64 IND and CD14 IND were calculated, and the
      peripheral blood WBC count, erythrocyte sedimentation rate (ESR) and C-reactive
      protein (CRP) were determined at the same time. RESULTS: The differences of nCD64
      IND and CRP between these 2 groups were statistically significant (P<0.05),
      however, the differences of CD14IND, ESR and WBC between these 2 groups were not
      statistically significant(P>0.05). The receiver operating curves (ROC) were drawn
      by using the data of all indictors in the 2 groups, and the order of the area
      under the curve(AUC) from big to small size was as follows:
      nCD64IND(0.974)>CRP(0.786)>ESR(0.675)>WBC(0.598)>CD14IND(0.556). The AUC of
      nCD64IND, CRP and ESR were statistically significantly different from the
      standard area of 0.5(P<0.05), while the AUC of CD14 IND,WBC were not
      statistically significantly different from the standard area of 0.5(P>0.05).
      CONCLUSION: nCD64 possesses a high diagnostic value for hematologic tumors with
      bacterial infection, it's sensitivity and specificity both are higher than that
      of CRP and ESR.

PMID- 29070146
TI  - [Research Progress on Molecular Mechanisms of Resistance to Bortezomib in
      Multiple Myeloma- Review].
AB  - Over the last decade, bortezomib(BTZ) has been extensively applied in the
      treatment of hematological malignancies, particularly in multiple myeloma and
      mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has
      brought a huge challenge in MM treatment. In the present review, the mechanisms
      of resistance to bortezomib in MM are summarized, focusing on the action of
      ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy,
      inducible pro-survival signalling and bone marrow microenvironment as well as
      exploration of the potential therapeutic strategies in the clinical perspective.
      With the understanding of the molecular mechanisms for resistance to BTZ, the
      novel histone deacetylase inhibitors(HDACi) have been approved for the treatment
      of replased/refractory MM and AKT inhibitor in the clinical trials. These novel
      combined therapies can enhance BTZ efficiency and improve the outcome of the
      patients.

PMID- 29070145
TI  - [Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras,
      BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients].
AB  - OBJECTIVE: To investigate the effect of ERK1 / 2 signaling pathway inhibitor
      PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for
      basic research and clinical treatment of the chronic mountain sickness(CMS).
      METHODS: Sixteen CMS patients were selected, the bone marrow was collected for
      isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and
      CD235a antibody magnetic beads, then positive cells were diveded into 5 groups:
      blank control, DMSO and PD98059 5, 10 and 20 umol/L, and were cultured in hypoxid
      condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA,
      the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in
      nucleated red blood cells, and the Western blot method was used to detect
      expression of BRaf, MEK, ERK1, ERK2 protein. RESULTS: PD98059 had no effect on
      the level of Ras-GTP in each groups. Compared with the blank control group, the
      expression levels of BRaf, MEK mRNA in DMSO group were not statistically
      significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L
      group, the expression level of ERK1/2 mRNA was statistically significant
      (P=0.001, 0.002). Compared with the blank control group, expression levels of p
      BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370,
      0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2
      protein level in other 4 groups were statistically significant (P values were
      <0.001, 0.007). CONCLUSION: PD98059 can up-regulate the expressions of ERK1/2
      miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras /
      Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating
      bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2
      pathway may be involved in the pathogenesis of chronic mountain sickness process.

PMID- 29070147
TI  - [Gene Mutation and Acute Leukemia Transformation of Severe Congenital Neutropenia
      Review].
AB  - Severe congenital neutropenia (SCN) is a rare disease of bone marrow failure.
      Absolute value of peripheral blood neutrophil of SCN significantly reduced. SCN
      has a high risk of transformation to myelodysplastic syndromes (MDS) / acute
      myeloid leukemia (AML). At present, there are 14 abnormal genes related to SCN,
      ELANE is the most common pathogenic gene, the main therapy of SCN is the
      application of granulocyte colony stimulating factor (G-CSF). CSF3R gene mutation
      often occurs in the treatment process, and can lead to acute myeloid leukemia.
      Further research on SCN/AML transformation mechanism is helpful to the diagnosis
      and treatment of this disease. This review focuses on the genetics and phenotypic
      polymorphysm in SCN patients, the therapeutic effect and risk of G-CSF for SCN
      patients, the effect of CSF3R matation on signal transduction of G-CSF, CSF3R
      mutation is important factor for SCN tranformation to acute myeloid leukemia,
      exploring the mechanism of SCN/AML transformation contributes to diagnosis and
      therapy for patients and so on.

PMID- 29070149
TI  - Use of Silver Diamine Fluoride for Dental Caries Management in Children and
      Adolescents, Including Those with Special Health Care Needs.
AB  - BACKGROUND: This manuscript presents evidence-based guidance on the use of 38
      percent silver diamine fluoride (SDF) for dental caries management in children
      and adolescents, including those with special health care needs. A guideline
      workgroup formed by the American Academy of Pediatric Dentistry developed
      guidance and an evidence-based recommendation regarding the application of 38
      percent SDF to arrest cavitated caries lesions in primary teeth. TYPES OF STUDIES
      REVIEWED: The basis of the guideline's recommendation is evidence from an
      existing systematic review "Clinical trials of silver diamine fluoride in
      arresting caries among children: A systematic review." (JDR Clin Transl Res
      2016;1[3]:201-10). A systematic search was conducted in PubMed(r)/MEDLINE,
      Embase(r), Cochrane Central Register of Controlled Trials, and gray literature
      databases to identify randomized controlled trials and systematic reviews
      reporting on the effect of silver diamine fluoride and address peripheral issues
      such as adverse effects and cost. The Grading of Recommendations Assessment,
      Development, and Evaluation (GRADE) approach was used to assess the quality of
      the evidence and the evidence-to-decision framework was employed to formulate a
      recommendation. RESULTS: The panel made a conditional recommendation regarding
      the use of 38 percent SDF for the arrest of cavitated caries lesions in primary
      teeth as part of a comprehensive caries management program. After taking into
      consideration the low cost of the treatment and the disease burden of caries,
      panel members were confident that the benefits of SDF application in the target
      populations outweigh its possible undesirable effects. Per GRADE, this is a
      conditional recommendation based on low-quality evidence. Conclusions and
      practical implications: The guideline intends to inform the clinical practices
      involving the application of 38 percent SDF to enhance dental caries management
      outcomes in children and adolescents, including those with special health care
      needs. These recommended practices are based upon the best available evidence to
      date. A 38 percent SDF protocol is included in Appendix II.

PMID- 29070150
TI  - Use of Vital Pulp Therapies in Primary Teeth with Deep Caries Lesions.
AB  - PURPOSE: This manuscript presents evidence-based guidance on the use of vital
      pulp therapies for treatment of deep caries lesions in children. A guideline
      panel convened by the American Academy of Pediatric Dentistry formulated evidence
      based recommendations on three vital pulp therapies: indirect pulp treatment
      (IPT; also known as indirect pulp cap), direct pulp cap (DPC), and pulpotomy.
      METHODS: The basis of the guideline's recommendations was evidence from "Primary
      Tooth Vital Pulp Therapy: A Systematic Review and Meta-Analysis." (Pediatr Dent
      2017;15;39[1]:16-23.) A systematic search was conducted in PubMed(r)/MEDLINE,
      Embase(r), Cochrane Central Register of Controlled Trials, and trial databases to
      identify randomized controlled trials and systematic reviews addressing
      peripheral issues of vital pulp therapies such as patient preferences of
      treatment and impact of cost. Quality of the evidence was assessed through the
      Grading of Recommendations Assessment, Development, and Evaluation approach; the
      evidence-to-decision framework was used to formulate a recommendation. RESULTS:
      The panel was unable to make a recommendation on superiority of any particular
      type of vital pulp therapy owing to lack of studies directly comparing these
      interventions. The panel recommends use of mineral trioxide aggregate (MTA) and
      formocresol in pulpotomy treatments; these are recommendations based on moderate
      quality evidence at 24 months. The panel made weak recommendations regarding
      choice of medicament in both IPT (moderate-quality evidence [24 months], low
      quality evidence [48 months]) and DPC (very-low quality evidence [24 months]).
      Success of both treatments was independent of type of medicament used. The panel
      also recommends use of ferric sulfate (low-quality evidence), lasers (low-quality
      evidence), sodium hypochlorite (very low-quality evidence), and tricalcium
      silicate (very low-quality evidence) in pulpotomies; these are weak
      recommendations based on low-quality evidence. The panel recommended against the
      use of calcium hydroxide as pulpotomy medicament in primary teeth with deep
      caries lesions. Conclusions and practical implications: The guideline intends to
      inform the clinical practices with evidence-based recommendations on vital pulp
      therapies in primary teeth with deep caries lesions. These recommendations are
      based upon the best available evidence to-date.

PMID- 29070151
TI  - Can Resident Research Provide The Evidence We Are Looking For?

PMID- 29070148
TI  - Molecular Mechanisms Driving Cholangiocarcinoma Invasiveness: An Overview.
AB  - The acquisition of invasive functions by tumor cells is a first and crucial step
      toward the development of metastasis, which nowadays represents the main cause of
      cancer-related death. Cholangiocarcinoma (CCA), a primary liver cancer
      originating from the biliary epithelium, typically develops intrahepatic or lymph
      node metastases at early stages, thus preventing the majority of patients from
      undergoing curative treatments, consistent with their very poor prognosis. As in
      most carcinomas, CCA cells gradually adopt a motile, mesenchymal-like phenotype,
      enabling them to cross the basement membrane, detach from the primary tumor, and
      invade the surrounding stroma. Unfortunately, little is known about the molecular
      mechanisms that synergistically orchestrate this proinvasive phenotypic switch.
      Autocrine and paracrine signals (cyto/chemokines, growth factors, and morphogens)
      permeating the tumor microenvironment undoubtedly play a prominent role in this
      context. Moreover, a number of recently identified signaling systems are
      currently drawing attention as putative mechanistic determinants of CCA cell
      invasion. They encompass transcription factors, protein kinases and phosphatases,
      ubiquitin ligases, adaptor proteins, and miRNAs, whose aberrant expression may
      result from either stochastic mutations or the abnormal activation of upstream
      pro-oncogenic pathways. Herein we sought to summarize the most relevant molecules
      in this field and to discuss their mechanism of action and potential prognostic
      relevance in CCA. Hopefully, a deeper knowledge of the molecular determinants of
      CCA invasiveness will help to identify clinically useful biomarkers and novel
      druggable targets, with the ultimate goal to develop innovative approaches to the
      management of this devastating malignancy.

PMID- 29070154
TI  - Letter to the Editor.

PMID- 29070153
TI  - Response to Letter to the Editor.

PMID- 29070155
TI  - Strengthening the American Academy of Pediatric Dentistry's Public Policy
      Advocate Network: Identifying Advocacy Efforts and Recommendations.
AB  - PURPOSE: The purposes of this study were to collect information on involvement,
      training, and barriers to participation in advocacy efforts for Public Policy
      Advocates (PPAs) of the American Academy of Pediatric Dentistry (AAPD) and make
      recommendations to the AAPD. METHODS: Preliminary data were collected from the
      PPAs during structured AAPD program meetings, conference calls, and individual
      interviews. Based on these data, a survey was created, piloted, and sent
      electronically to all PPAs. Data were analyzed and collated by frequencies.
      RESULTS: Responses from 38 PPAs (100 percent) revealed they were involved with
      state legislatures and state chapters of the AAPD and American Dental
      Association. Eighty-two percent of the PPAs requested additional public policy
      training and clearer communication channels within the network. PPAs are funding
      their own advocacy efforts, and the time and resources spent away from patient
      care is a financial barrier. CONCLUSIONS: The Public Policy Advocate network
      holds a broad policy skill set and voluntarily commits time and resource to
      advocate for the support of the pediatric dental patient at state and federal
      government levels. The American Academy of Pediatric Dentistry can strengthen the
      PPA's self-directed leadership role at state and federal levels through
      formalized training, restructuring of the network, and increased resources.

PMID- 29070156
TI  - Born Into Addiction: Neonatal Abstinence Syndrome and Pediatric Dentistry.
AB  - Drug overdose and opioid-involved deaths continue to increase across the United
      States. An end-condition related to opioid abuse is neonatal abstinence syndrome
      (NAS). The implications for pregnant or post-partum women using an opioid,
      whether prescribed or illicit, can have significant effects on their infant.
      First described in the 1970s, NAS is defined as a postnatal drug withdrawal
      syndrome that primarily occurs in opioid-exposed infants. There are no nationally
      accepted, evidence-based treatment protocols for these infants. Pediatric
      dentists should be cognizant of potential dental development issues and
      developmental delays in children with NAS. Basic behavior guidance techniques,
      such as tell-show-do, may not be as effective. In addition, adherence to
      prescription drug monitoring programs can help identify patients who may have
      received multiple opioids, alerting the provider to possible misuse or abuse. The
      purpose of this paper was to provide background information on the incidences and
      potential dental implications for children with neonatal abstinence syndrome.

PMID- 29070157
TI  - Academic Pediatric Dentistry is a Rewarding, Financially Viable Career Path.
AB  - Newly graduated pediatric dentists have unprecedented levels of debt. High levels
      of student debt may be perceived as an obstacle to pursue an academic career.
      However, opportunities exist through faculty compensation models and loan
      repayment programs that make an academic career financially viable. The purpose
      of this paper is to outline the benefits of a career in academic dentistry and
      provide examples of young pediatric dentistry faculty members who have been able
      to manage student debt while pursuing meaningful and rewarding careers.

PMID- 29070158
TI  - Partial Pulpotomy in Immature Permanent Molars After Carious Exposures Using
      Different Hemorrhage Control and Capping Materials.
AB  - PURPOSE: This study compared the outcome of partial pulpotomies with mineral
      trioxide aggregate (MTA) or calcium hydroxide (CH) following hemorrhage control
      with 2.5 percent sodium hypochlorite (SH) or 0.9 percent sterile saline (SS)
      solutions in cariously exposed immature permanent molars. METHODS: Following
      removal of two to three mm of the pulp at the exposure site, 80 Class I cavities
      were randomly allocated to four groups according to the hemorrhage control agent
      and pulp-capping material used: (1) group one-SH plus MTA; (2) group two-SS plus
      MTA; (3) group three-SH plus CH; (4) group four-SS plus CH. Glass ionomer cement
      was applied over the pulp-capping material, and the teeth were later restored
      with composite resin. The patients were recalled at six, 12, 18, and 24 months.
      RESULTS: After 24 months, simultaneous radiographic and clinical success rates
      were 94.4 percent, 100 percent, 95 percent, and 100 percent for groups one to
      four, respectively (P>.05). No significant correlation was found between marginal
      integrity scores of restorations and partial pulpotomy failure (P>.05).
      CONCLUSIONS: Partial pulpotomy, performed with MTA or CH used as the pulp-capping
      material following hemostasis with SH or SS solutions, provided comparable and
      favorable outcomes in carious pulp exposures of immature permanent teeth.

PMID- 29070159
TI  - Performance of Universal Adhesive in Primary Molars After Selective Removal of
      Carious Tissue: An 18-Month Randomized Clinical Trial.
AB  - PURPOSE: To evaluate the 18-month clinical performance of a universal adhesive,
      applied under different adhesion strategies, after selective carious tissue
      removal in primary molars. METHODS: Forty-four subjects (five to 10 years old)
      contributed with 90 primary molars presenting moderately deep dentin carious
      lesions on occlusal or occluso-proximal surfaces, which were randomly assigned
      following either self-etch or etch-and-rinse protocol of Scotchbond Universal
      Adhesive (3M ESPE). Resin composite was incrementally inserted for all
      restorations. Restorations were evaluated at one, six, 12, and 18 months using
      the modified United States Public Health Service criteria. Survival estimates for
      restorations' longevity were evaluated using the Kaplan-Meier method.
      Multivariate Cox regression analysis with shared frailty to assess the factors
      associated with failures (P<0.05). RESULTS: Estimated survival rates of the
      restorations were 100 percent, 100 percent, 90.6 percent, and 81.4 percent at
      one, six, 12, and 18 months, respectively. The adhesion strategy did not
      influence the restorations' longevity (P=0.06; 72.2 percent and 89.7 percent with
      etch-and-rinse and self-etch mode, respectively). CONCLUSION: Self-etch and etch
      and-rinse strategies did not influence the clinical behavior of universal
      adhesive used in primary molars after selective carious tissue removal; although
      there was a tendency for better outcome of the self-etch strategy.

PMID- 29070160
TI  - Bioactive Tricalcium Silicate-based Dentin Substitute as an Indirect Pulp Capping
      Material for Primary Teeth: A 12-month Follow-up.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical and radiographic
      outcomes of a bioactive tricalcium silicate [Ca3SiO5]-based dentin substitute and
      a light-activated calcium hydroxide [Ca(OH)2]-based liner as indirect pulp
      treatment (IPT) interventions for vital primary molars with carious lesions
      approaching the pulp. METHODS: Eighty children, aged four to eight years old,
      with 160 bilateral primary teeth without signs or symptoms of irreversibly
      inflamed or degenerative pulp tissue were treated in a split-mouth design trial
      comparing IPT using Ca3SiO5 or Ca(OH)2. The teeth were treated and restored with
      a preformed crown in a single session and assessed clinically and
      radiographically for one, three, six, and 12 months. RESULTS: Sixty patients with
      120 treated molars completed the 12-month evaluations. The combined clinical and
      radiographic success rates were 98.3 percent (59 out of 60) for Ca3SiO5 and 95
      percent for Ca(OH)2 (57 out of 60). No significant differences were found for
      success rates between the two study groups (P>0.05). The combined success rates
      for both groups was 96.7 percent. CONCLUSIONS: These results suggest that the
      indirect pulp treatment procedure with either a bioactive Ca3SiO5-based dentin
      substitute or a Ca(OH)2-based material may be considered a suitable treatment to
      achieve acceptable therapeutic results when applied on deeply carious primary
      teeth without degenerative symptoms.

PMID- 29070161
TI  - HPV Vaccination and the Role of the Pediatric Dentist: Survey of Graduate Program
      Directors.
AB  - PURPOSE: This study's purpose was to evaluate what is currently being taught in
      graduate pediatric dental programs regarding the human papillomavirus (HPV), the
      HPV vaccine, and risk factors associated with oropharyngeal cancer (OPC).
      METHODS: A 42-question survey was administered via paper-and-pen survey
      instrument to attendees at the 2016 American Academy of Pediatric Dentistry
      (AAPD) annual meeting for graduate and associate program directors. The survey
      included questions evaluating attitudes/beliefs toward the HPV vaccine and
      current training in graduate pediatric dentistry programs and aimed to define
      whether the directors believe that the discussion of HPV vaccination and
      associated risk factors was within the scope of practice for pediatric dentists.
      RESULTS: Sixty-four of 71 attendees completed the survey; 77 percent of
      respondents believe they should be discussing the HPV vaccine with
      patients/parents. Increased age of respondent was correlated with the idea of
      discussion of sexual health and its link to OPC being within the scope of
      practice of pediatric dentistry (r equals 0.35, P=.005). CONCLUSIONS: A majority
      (77 percent) of graduate and associate program directors believe they should be
      discussing the human papillomavirus vaccine with patients and parents; however,
      only 25 percent of respondents currently include information about HPV and the
      vaccine in their curricula.

PMID- 29070162
TI  - Pediatric Dentists' Attitudes, Perceptions, and Experience with the Affordable
      Care Act.
AB  - PURPOSE: Pediatric oral health benefits were designated as one of 10 Essential
      Health Benefits (EHB) in the Affordable Care Act. Although it provided coverage
      for many children, several issues prevent its success. The purpose of this study
      was to document experience with, attitudes toward, and perceptions of the
      Affordable Care Act (ACA) among pediatric dentists. METHODS: The study was
      conducted using a survey consisting of nine multiple choice questions and one
      open-ended item and was distributed electronically in November 2015 to active and
      life members of the American Academy of Pediatric Dentistry. RESULTS: Respondents
      reported patients deferring treatment due to high out-of-pocket costs. Providers
      perceive that patients do not have enough information to understand their
      benefits. Providers reported not having enough information to understand how
      these benefits affect their practices. CONCLUSIONS: Pediatric dentists report
      deferral of both preventive and restorative care due to high out-of-pocket costs.
      Pediatric dentists do not feel they have adequate information regarding the
      Affordable Care Act and its effect on their practices. The majority of pediatric
      dentists believe that parents have difficulty understanding their children's
      benefits.

PMID- 29070163
TI  - Dental Caries Experience in Texan Children with Cleft Lip and Palate.
AB  - PURPOSE: The purpose of this study was to assess the caries experience in the
      primary dentition of children born with cleft lip and palate (CLP). METHODS: A
      retrospective chart review was conducted on subjects between two and six years
      old recruited from a university-based pediatric dentistry residency clinic. The
      number of dental visits and professional fluoride applications, the plaque index
      and treatment modality, and the presence/location of caries, white spot lesions,
      and enamel hypoplastic lesions were compared between CLP patients and healthy age
      and gender-matched controls. Descriptive statistics, Student's t test, Mann
      Whitney U test, and regression analysis were completed. RESULTS: A total of 183
      charts were reviewed. Compared to healthy children, CLP children had increases in
      number of dental visits (P<0.001), decayed-missing-filled surfaces (dmfs;
      P<0.001), decayed-missing-filled teeth (dmft; P<0.001), enamel hypoplastic
      lesions (P=0.003), treatment completed under general anesthesia (P<0.001), plaque
      score (P<0.001), and caries increment between baseline and most recent oral
      examination (P=0.003). Regression analysis revealed a positive association
      between age and dmft scores within the CLP group (P=0.018). The caries experience
      of unilateral and bilateral CLP cases was the same (P>0.05). CONCLUSIONS:
      Children with cleft lip and palate are at a greater risk of enamel hypoplasia and
      dental caries. No significant caries experience difference was found between
      unilateral or bilateral CLP cases.

PMID- 29070164
TI  - Development of an LC-MS/MS Determination Method for T-2 Toxin and Its Glucoside
      and Acetyl Derivatives for Estimating the Contamination of Total T-2 Toxins in
      Staple Flours.
AB  - A determination method previously validated for trichothecenes and zearalenone by
      means of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was adapted
      for the quantification of T-2 toxin (T-2) as well as its glucoside and acetyl
      derivatives, T-2-3-glucoside (T-2-3G) and 3-acetyl-T-2 (3A-T-2). HT-2 toxin (HT
      2) and its acetyl derivative 3-acetyl-HT-2 (3A-HT-2) were also included as the
      target chemicals. Staple flours (56 samples collected from the Singapore market)
      were examined for contamination from T-2 and/or HT-2 and their derivatives. Among
      them, 16 flours were found to be contaminated with T-2 and/or HT-2, whereas none
      was contaminated with T-2-3G and 3A-HT-2, except for trace 3A-T-2 detected in 2
      rye samples. Rye flour samples were frequently contaminated with both T-2 and HT
      2. Some of the reference materials (RMs) were further analyzed, and T-2-3G and 3A
      T-2 were quantitatively detected in corn and wheat RMs. The ratio of T-2-3G to T
      2 in the RMs seemed to be much lower than the ratio of deoxynivalenol-3-glucoside
      to deoxynivalenol usually reported in former studies. To the best of our
      knowledge, the natural contamination of 3A-T-2 in staple flour is reported here
      for the first time.

PMID- 29070165
TI  - Optimal cutoff values of allergen-specific immunoglobulin E to house dust mites
      and animal dander based on skin-prick test results: Analysis in 16,209 patients
      with allergic rhinitis.
AB  - BACKGROUND: The most common tests for allergen sensitization in patients with
      allergic rhinitis are the skin-prick test(SPT) and an in vitro test to detect
      serum specific immunoglobulin E (sIgE). However, in vitro allergen test results
      were interpreted dichotomically as positive or negative at a threshold of
      0.35kU/L of sIgE, regardless of the patient characteristics or antigen types.
      OBJECTIVE: The purpose of this study was to determine the cutoff value for sIgE
      in house-dust mites and animal dander, and to analyze differences in cutoff value
      according to age and gender. METHODS: A total of 16,209 patients with more than
      one allergic rhinitis symptom who underwent both SPT and serum sIgE testing were
      retrospectively evaluated between March 2008 and May 2012. There were 9374 male
      (57.8%) and 6835 female (42.2%) patients. The mean age was 31.8 years (range, 2
      89 years). The criterion standard for allergen sensitization was defined as a
      wheal of > 3 mm or an allergen-to-histamine ratio of greater than or equal to 1
      in SPT results. The Youden index was used to calculate the cutoff value of sIgE.
      RESULTS: Cutoff values of sIgE for Dermatophagoides pteronyssinus,
      Dermatophagoides farinae, cat, and dog were 0.69, 1.16, 0.13, and 0.45 kU/L,
      respectively. The cutoff value of sIgE changed according to age for D.
      pteronyssinus and D. farinae but not for cat and dog allergens. When
      categorizingaccording to age group, the cutoff values of sIgE for D.
      pteronyssinus and D. farinae had a tendency to decrease with age. There was no
      significant difference in cutoff value according to gender. CONCLUSION: The
      cutoff value for sIgE differed for each antigen and changed with age. Physicians
      should select the proper cutoff value for sIgE for appropriate criteria according
      to antigen and patient age rather than using a uniform cutoff value.

PMID- 29070181
TI  - In reply.

PMID- 29070186
TI  - Using the nasoseptal flap for reconstruction after endoscopic debridement of
      radionecrosis in nasopharyngeal carcinoma.
AB  - BACKGROUND: Radionecrosis is a complication of nasopharyngeal carcinoma (NPC)
      that is difficult to treat. Endoscopic debridement is the first-line treatment
      for radionecrosis. After debridement, however, either bone or the internal
      carotid artery is exposed and requires mucosal coverage. OBJECTIVES: This study
      sought to demonstrate the effectiveness of a nasoseptal flap (NSF) after
      endoscopic debridement of radionecrosis in the reconstruction of nasopharyngeal
      or skull base defects. METHODS: Nine patients with NPC who underwent navigation
      guided endoscopic debridement, followed by NSF reconstruction between April 2013
      and July 2016, were included. The patients' clinical features and outcomes were
      evaluated. RESULTS: All nine patients had headaches, and eight had a foul odor
      associated with their radionecrosis. One patient underwent three radiotherapy
      treatments, four had two treatments, and the remaining four had just one
      treatment. The foul odor disappeared after treatment in all the patients who had
      beenaffected. The headache was significantly reduced after treatment in all
      patients. The NSF detached in two patients. In one patient, NSF failed, and the
      patientexperienced postoperative rupture of the internal carotid artery. In the
      seven other patients, the NSF successfully covered the resultant defects, despite
      one intraoperative internal carotid artery rupture. Only two patients required
      further debridement, whereas the others experienced complete healing after just
      one surgical procedure. The nasopharyngeal surface was healthy-appearing in eight
      patients (median follow-up, median 11 months). CONCLUSION: Reconstruction by
      using NSF after endoscopic debridement for radionecrosis of NPC allowed for
      faster healing and reduced the need for further debridement.

PMID- 29070203
TI  - Erratum.
AB  - IN THE ARTICLE entitled 'Compliance surveys: an effective tool to validate smoke
      free public places in four jurisdictions in India' by P. G. Lal, N. C. Wilson, R.
      J. Singh (Int J Tuberc Lung Dis 2011; 15(4): 565-566;
      http://dx.doi.org/10.5588/ijtld.10.0372), an error occurred in the wording of the
      Table.

PMID- 29070234
TI  - Errata.
AB  - IN THE ARTICLE entitled 'HIV-positive patients treated for multidrug-resistant
      tuberculosis: clinical outcomes in the HAART era' by E. Palacios, M. Franke, M.
      Munoz, et al. (Int J Tuberc Lung Dis 2012; 16(3): 348-354;
      http://dx.doi.org/10.5588/ijtld.11.0473), the name of author M. Lyzigos was spelt
      incorrectly. It should read: M. Lygizos.

PMID- 29070235
TI  - Errata.
AB  - IN THE ARTICLE entitled 'Patient and doctor perspectives on incorporating smoking
      cessation into tuberculosis care in Beijing, China' by S. S. Shin, D. Xiao, M.
      Cao, et al. (Int J Tuberc Lung Dis 2012; 16(1): 126-131;
      http://dx.doi.org/10.5588/ijtld.11.0044), the affiliations for authors M. Cao and
      Q. Li should have read Beijing Chest Hospital, Capital Medical University. The
      following footnote was also omitted from the title page: 'SSS, DX, MC, CW and QL
      contributed equally to this study'.

PMID- 29070251
TI  - In reply to 'Should Xpert(r) MTB/RIF be rolled out in low-income countries?'
      [Correspondence].

PMID- 29070250
TI  - In reply to 'Location of Xpert(r) MTB/RIF in centralised laboratories in South
      Africa undermines potential impact' [Correspondence].

PMID- 29070259
TI  - In reply to 'Geographic variability in COPD prevalence' [Correspondence].

PMID- 29070267
TI  - Barosinusitis: Comprehensive review and proposed new classification system.
AB  - BACKGROUND: Barosinusitis, or sinus barotrauma, may arise from changes in ambient
      pressure that are not compensated by force equalization mechanisms within the
      paranasal sinuses. Barosinusitis is most commonly seen with barometric changes
      during flight or diving. Understanding and better classifying the
      pathophysiology, clinical presentation, and management of barosinusitis are
      essential to improve patient care. OBJECTIVES: To perform a comprehensive review
      of the available literature regarding sinus barotrauma. METHODS: A comprehensive
      literature search that used the terms "barosinusitis," "sinus barotrauma," and
      "aerosinusitis" was conducted, and all identified titles were reviewed for
      relevance to the upper airway and paranasal sinuses. All case reports, series,
      and review articles that were identified from this search were included. Selected
      cases of sinus barotrauma from our institution were included to illustrate
      classic signs and symptoms. RESULTS: Fifty-one articles were identified as
      specifically relevant to, or referencing, barosinusitis and were incorporated
      into this review. The majority of articles focused on barosinusitis in the
      context of a single specific etiology rather than independent of etiology. From
      analysis of all the publications combined with clinical experience, we proposed
      that barosinusitis seemed to fall within three distinct subtypes: (1) acute,
      isolated barosinusitis; (2) recurrent acute barosinusitis; and (3) chronic
      barosinusitis. We introduced this terminology and suggested independent treatment
      recommendations for each subtype. CONCLUSION: Barosinusitis is a common but
      potentially overlooked condition that is primed by shifts in the ambient pressure
      within the paranasal sinuses. The pathophysiology of barosinusitis has disparate
      causes, which likely contribute to its misdiagnosis and underdiagnosis. Available
      literature compelled our proposed modifications to existing classification
      schemes, which may allow for improved awareness and management strategies for
      barosinusitis.

PMID- 29070268
TI  - Evaluation of a new and simple classification for endoscopic sinus surgery.
AB  - OBJECTIVE: In 2013, the Japanese Rhinologic Society proposed a simple
      classification for endoscopic sinus surgery (ESS). This classification consists
      of five procedures (type I, fenestration of the ostiomeatal complex, with
      uncinectomy and widening of the natural ostium; type II, single-sinus procedure,
      with manipulating the inside of the sinus; type III, polysinus procedure; type
      IV, pansinus procedure; type V, extended procedure beyond the sinus wall). The
      clinical relevance of this classification in chronic rhinosinusitis (CRS) and
      paranasal sinus cyst was evaluated. STUDY DESIGN: A retrospective validation
      study. METHODS: A total of 122 patients (195 sinuses) who underwent ESS in
      Okayama University Hospital in 2012 were enrolled. The relationships between the
      ESS classification and the clinical course, including the operation time,
      bleeding amounts during surgery and postoperative changes of olfaction, the
      computed tomography (CT) score, and nasal airway resistance were analyzed.
      RESULTS: A total of 195 ESS procedures were classified into type I (n = 3), type
      II (n = 17), type III (n = 91), type IV (n = 82), and type V (n = 2). The major
      phenotypes of type II, III, and IV ESS were paranasal sinus cyst (68%), CRS
      without nasal polyps (77%), and CRS with nasal polyps (55%), respectively, and
      the difference was significant. The degree of ESS based on this classification
      was positively and significantly correlated with the operation time and bleeding
      amounts. As a whole, olfaction, CT score, and nasal airway resistance were
      significantly improved after surgery. The degree of improvement was similar
      between type III and type IV ESS. CONCLUSION: This simple classification for ESS
      reflected the perioperative burden of the disease.

PMID- 29070269
TI  - The study of a possible correlation between serum levels of interleukin 17 and
      clinical severity in patients with allergic rhinitis.
AB  - INTRODUCTION: Allergic rhinitis (AR) is one of the most common allergic diseases,
      which affects ~20% of the world's population. T-helper (Th) type 2 cells produce
      interleukin (IL) 4 and IL-13, and mediate allergic responses, and these cytokines
      have been extensively studied as key players in the atopic airway diseases.
      However, the involvement of Th17 cells and IL-17 in AR has not been clearly
      examined. AIM: To reevaluate AR clinical severity with serum IL-17, whether IL-17
      affects the disease alone or in contribution with the atopic predisposition.
      PATIENTS AND METHODS: During an 18-month period, 39 individuals were divided into
      three groups: A, (13 control), B (13 with mild-to-moderate AR), and C (13 with
      severe AR). Both group B and group C patients (26) were subjected to clinical
      examination and allergy skin testing, and to measurement of both total serum
      immunoglobulin E (IgE) and IL-17 levels. Eleven patients with AR then were
      exposed to 6 months of cluster immunotherapy, whereas the rest of the patients
      were not exposed. RESULTS: Revealed a significant elevation of serum IL-17 levels
      with an associated increase in serum IgE in the patients with AR compared with
      controls and revealed that the serum levels of both total serum IgE and IL-17
      decreased significantly after cluster immunotherapy. CONCLUSION: These
      preliminary results added new data about the use of injective immunotherapy as
      well as reported on the use of sublingual immunotherapy.

PMID- 29070270
TI  - Prenatal maternal depression related to allergic rhinoconjunctivitis in the first
      5 years of life in children of the EDEN mother-child cohort study.
AB  - : Backgroud: Evidence about the relationship between prenatal maternal depression
      and the development of childhood asthma and allergies in early life is scarce. We
      aimed to examine this relationship by using data set of EDEN mother-child cohort
      study. A total of 1139 children were followed-up until the age of 5 years.
      METHODS: Prenatal maternal depression was self-reported by using the Centre for
      Epidemiological Studies-Depression scale (CES-D) questionnaire and was classified
      into binary variable (maternal depression [CES-D score of >=16] and no maternal
      depression [CES-D score of <16]). Asthma and allergies in the first 5 years were
      assessed by using the questionnaire of the International Study of Asthma and
      Allergies in Childhood (ISAAC). Adjusted odds ratio (aOR) was estimated for the
      relationship between prenatal maternal depression and early life asthma and
      allergies by marginal models through the method of generalized estimating
      equation (GEE) when adjusting for the confounders. RESULTS: In our study
      population, 13.67 % of the mothers had clinical significant depression (the total
      scores for CES-D >=16) during pregnancy. For children ages 5 years, the
      prevalence of wheezing, physician-diagnosed asthma, physician-diagnosed eczema
      and allergic rhinoconjunctivitis were 46.78, 20.99, 29.17, and 22.54%,
      respectively. Prenatal maternal depression was associated with ever allergic
      rhinoconjunctivitis (aOR 1.87 [95% confidence interval {CI}, 1.33-2.62]). No
      significant relationships were found between prenatal maternal depression and
      wheezing, physician-diagnosed asthma and physician-diagnosed eczema (aOR 1.12
      [95% CI, 0.91-1.39], aOR 1.23 [95% CI, 0.81-1.85] and aOR 1.17 [95% CI, 0.86
      1.61], respecitvely). CONCLUSION: Prenatal maternal depression was related to
      ever allergic rhinoconjunctivitis in the first 5 years of life in children of
      EDEN mother-child cohort study.

PMID- 29070271
TI  - Characterization of T-cell subpopulations in patients with chronic rhinosinusitis
      with nasal polyposis.
AB  - BACKGROUND: There is an ongoing discussion concerning the potential origins of
      chronic rhinosinusitis with nasal polyposis (CRSwNP). OBJECTIVE: The aim of this
      study was to quantify subpopulations of T cells in peripheral blood and nasal
      polyps in CRSwNP to examine their influence on the etiology of this disease.
      METHODS: Tissue and blood samples were collected from 11 patients who underwent
      nasal sinus surgery, and these samples were analyzed by multicolor flow
      cytometry. RESULTS: There was a significantly lower frequency of CD4+ T-helper
      (Th) cells and a significantly higher frequency of CD8+ T cells among lymphocytes
      isolated from nasal polyps compared with peripheral blood mononuclear cells
      (PBMC). In both T-cell subpopulations, a shift mainly from naive T cells among
      peripheral blood lymphocytes toward an effector memory and terminally
      differentiated subtype predominance in nasal polyps was observed. Among CD4+ T
      cells, the frequencies of cluster of differentiation (CD) 45RA- Forkhead-Box
      Protein P3high (FoxP3high) cytotoxic T-lymphocyte-associated Protein 4high (CTLA
      4high) activated regulatory T (Treg) cells, and CD45RA- Forkhead-Box-Protein
      P3low (FoxP3low) memory T cells were significantly increased in nasal polyps
      compared with PBMC. CONCLUSION: In this study, we presented a detailed
      characterization of CD4+ and CD8+ T-cell subpopulations in patients with CRSwNP.
      CD8+ T cells were more prominent in nasal polyps than in CD4+ T cells. Both nasal
      CD8+ T cells and CD4+ T cells predominantly had an effector memory phenotype.
      Among CD4+ T cells, activated Treg cells were increased in nasal polyps compared
      with PBMC. The data point toward a local regulation of T-cell composition within
      the microenvironment of nasal polyps, which might be further exploited in the
      future to develop novel immunotherapeutic strategies.

PMID- 29070272
TI  - A multicenter, prospective, noninterventional study in a Norwegian cohort of
      patients with moderate-to-severe allergic rhinitis treated with MP-AzeFlu.
AB  - BACKGROUND: Allergic Rhinitis and its Impact on Asthma guidelines recently
      recommended a treatment strategy for allergic rhinitis (AR) based on disease
      control rather than symptom severity by using a visual analog scale (VAS) to
      categorize control. OBJECTIVES: To evaluate the effectiveness of MP-AzeFlu
      (Dymista(r)) by using this VAS in routine clinical practice in Norway. MP-AzeFlu
      comprises a novel formulation that contains azelastine hydrochloride, fluticasone
      propionate and excipients delivered in a single spray. METHODS: This multicenter,
      prospective, noninterventional study enrolled patients (n = 160) with moderate-to
      severe AR and acute symptoms who were eligible to receive treatment with MP
      AzeFlu according to its summary of product characteristics. Patients assessed
      symptom severity by using a VAS from 0 (not at all bothersome) to 100 mm (very
      bothersome) in the morning before MP-AzeFlu use on days 0, 1, 3, 7, and after ~14
      days. On day 3, the patients assessed their level of disease control as well
      controlled, partly controlled, or uncontrolled. The proportion of Norwegian
      patients who achieved defined VAS score cutoffs for "well-controlled" and "partly
      controlled" AR were also calculated. RESULTS: MP-AzeFlu reduced the mean +/-
      standard deviation VAS score from 68.1 +/- 16.4 mm at baseline to 37.4 +/- 25.9
      mm on the last day, a reduction of 30.8 +/- 27.2 mm. The results were consistent,
      irrespective of disease severity, phenotype (i.e., seasonal AR [SAR], perennial
      AR [PAR], SAR plus PAR, unknown) or age (i.e., 12-17, 18-65, and >65 years). Of
      the patients (with recorded data), 88.1% considered their symptoms to be partly
      or well controlled at day 3; and 19.5, 32.0, 50.0, and 61.0% of the patients
      achieved a <=38 mm well-controlled VAS score cutoff on days 1, 3, 7, and the last
      day, respectively. CONCLUSIONS: MP-AzeFlu provided rapid sustained symptom
      control in a routine clinical practice in Norway, which provided support for its
      effectiveness for the treatment of AR in real life.

PMID- 29070273
TI  - Oral immunotherapy in children with IgE-mediated hen's egg allergy: Follow-ups at
      2.5 and 7 years.
AB  - BACKGROUND: The present report was a follow-up investigation at 2.5- and 7-year
      intervals of a previous study of 20 children with moderate-to-severe
      immunoglobulin E (IgE) mediated hen's egg (HE) allergy who received oral
      immunotherapy (OIT) with raw HE. The study design of the previous study divided
      the 20 subjects into two groups of 10 each: (1) group 1, the OIT group (OIT-G),
      and, (2) group 2, an age-matched control group (C-G). In that study, 8 of 10 of
      the children in the OIT-G were successfully desensitized, one child was partially
      desensitized, and desensitization failed in one child. The aims of the present
      study were to evaluate the long-term effectiveness and safety profile of OIT with
      raw HE, and to assess the course and prognostic value of skin-prick tests (SPT)
      and serum-specific HE-IgEs in this study population. METHODS: Of the 20 children
      who were recalled, 2 dropped out, which left 18 to be evaluated. Information on
      their HE intake was recorded, and SPTs with HE allergen extracts and with raw and
      hard-boiled HE were performed. Ovomucoid- and ovalbumin-specific IgE levels were
      also measured. RESULTS: At the first (2.5-year) and second (7-year) follow-ups,
      87.5% of the children in the OIT-G who tolerated raw HE were still tolerant,
      whereas the children in the C-G were significantly less tolerant. Overall,
      cutaneous sensitivity to HE significantly decreased after the 6-month
      desensitization period and at both follow-ups with regard to the OIT-G but not
      with regard to the C-G. A significant reduction in serum ovomucoid- and ovalbumin
      specific IgE levels was seen in both the OIT-G and the C-G. CONCLUSION: Clinical
      raw HE tolerance induced by OIT persists over time. Negativization of SPTs could
      be considered a more reliable prognostic indicator of clinical tolerance to raw
      HE than the reduction in specific-HE IgE levels. Raw-HE OIT would seem to be a
      promising method to treat HE allergy.

PMID- 29070274
TI  - Long-term omalizumab use in the treatment of exercise-induced anaphylaxis.
AB  - Reported is a case of a 39-year-old male who was diagnosed with exercise-induced
      anaphylaxis (EIA). He was initially treated prophylactically with fexofenadine,
      montelukast, and ranitidine. He also used an epinephrine autoinjector as needed.
      He was refractory to these medications and continued to have episodes of EIA. He
      was then started on a trial of omalizumab, an immunoglobulin E monoclonal
      antibody, and had resolution of the EIA episodes. After discontinuation of the
      omalizumab, the EIA episodes returned. He was restarted on omalizumab and since
      that time, has had 5 years free of EIA episodes and can now exercise without any
      symptoms. To our knowledge, this is only the third case in the literature of
      successful treatment of EIA by using omalizumab. This case was unique because it
      provided successful long-term use of omalizumab for EIA. Further studies are
      recommended for the use of omalizumab in the treatment of EIA.

PMID- 29070275
TI  - Long-term follow-up of a patient with malignant transformation of inverted
      papilloma into sinonasal undifferentiated carcinoma.
AB  - INTRODUCTION: Inverted papillomas (IP) are benign sinonasal neoplasms, which
      account for 0.5-4% of all nasal tumors. IPs have been known to transform into
      squamous cell carcinoma in 5-15% of cases. Rarely, transformations to other
      malignancies have been reported. Here we report a unique case of malignant
      transformation of an IP into sinonasal undifferentiated carcinoma (SNUC).
      METHODS: A case report with a literature review; institutional review board
      exempted. The clinical presentation, radiographic features, surgical
      intervention, histopathologic analysis, treatment, and outcome of the case were
      examined. RESULTS: A 62-year-old man presented with a 3-month history of nasal
      airway obstruction, rhinorrhea, and postnasal drip refractory to medical therapy.
      He had a long history of exposure to fumes, chemicals, dusts, and solvents as a
      professional painter as well as a 45 pack-year history of smoking and alcohol
      abuse. The patient was ultimately found to have a left ethmoidal IP with a focus
      of malignant transformation into SNUC. Endoscopic resection was performed,
      followed by concurrent chemoradiation and adjuvant chemotherapy. After surgery,
      he had no evidence of recurrent disease after 9 years of follow-up. CONCLUSIONS:
      IP is known to transform into squamous cell carcinoma. Here we report a rare case
      of malignant transformation into SNUC, a much more uncommon and aggressive
      lesion. Although traditionally associated with a poorer prognosis, the positive
      outcome for SNUC observed in this patient may potentially be attributed to early
      detection and timely therapeutic intervention.

PMID- 29070289
TI  - Tuberculosis and acute coronary syndrome [Correspondence].

PMID- 29070276
TI  - Multiple doses of icatibant used during pregnancy.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a life-long disease that often
      manifests by puberty. Treatment of attacks is essential to improve quality of
      life and to decrease morbidity and mortality. During pregnancy, treatment is
      limited because multiple treatment options, including icatibant, are not approved
      for use during pregnancy. OBJECTIVE: We report the outcomes of three pregnancies
      during which icatibant was used by a patient with HAE with normal C1-inhibitor
      for treatment of attacks. We also reviewed the literature for reports of
      icatibant use during pregnancy for outcomes and adverse events. METHODS: We
      report on a patient who treated herself with icatibant during three separate
      pregnancies. Postpartum follow-up verified the health of the mother and children.
      We also performed a complete literature search of medical literature data bases
      on icatibant use during pregnancy. RESULTS: The patient in our report
      administered multiple doses of icatibant during three pregnancies. The child born
      from the first pregnancy and the child from the third pregnancy were born at term
      and without congenital anomalies. The child from the second pregnancy was 1-month
      preterm. All three children were developmentally normal. The literature search
      identified two case reports and one abstract of limited icatibant use without
      adverse events during pregnancy in patients with HAE. These pregnancies resulted
      in the births of healthy infants. CONCLUSION: From a search of the literature,
      three cases of icatibant use during pregnancy resulted in healthy infants. In
      addition, we report that from icatibant use in three separate pregnancies, one
      infant was born prematurely, but there were no birth defects. From follow-up, the
      children continued meeting developmental milestones. This report adds to the
      acquisition of knowledge for drug adverse events during postmarketing
      surveillance for icatibant use during pregnancy.

PMID- 29070277
TI  - An ergonomic assessment of operating table and surgical stool heights for seated
      otolaryngology procedures.
AB  - BACKGROUND: Musculoskeletal injuries, such as neck and back pain, during a
      surgeon's career are common. However, studies on ergonomics are limited with
      regard to seated otolaryngologic procedures. Key elements of an ergonomic
      operating environment include the height of operating tables and surgical chairs.
      Surgeons benefit from proper support and positioning to prevent musculoskeletal
      injuries and reduce occupational risk. OBJECTIVE: The purpose of this study was
      to evaluate operating table and surgical seat heights, and determine whether
      adjustments can be made for various surgeon physiques. METHODS: Operating tables
      and surgical seat dimensions were measured at local hospitals, and the
      information was complemented by an online search of other models. RESULTS: Five
      unique operating tables and five unique surgical stools were identified, both in
      the local hospital and in a search on the Internet. Of available tables, the
      greatest range was 63.5-124.5 cm, which reaches above the maximum suggested
      working height of 76.2 cm. The surgical stool with the widest range was
      adjustable from heights of 50.8-72.4 cm. This combination of operative table and
      surgical stool provided the greatest range of heights. CONCLUSION: Of the
      available tables and stools measured, the combination of surgical table with a
      range of 63.5-125.7 cm and surgical stool with a range of 50.8-72.4 cm provided
      the greatest versatility for diverse physician heights. In ergonomic terms, this
      combination may reduce physical fatigue and create a potentially safer working
      environment for seated surgeons.

PMID- 29070333
TI  - In reply to 'Delay in tuberculosis diagnosis and treatment: what about smear and
      mycobacteriological status?' [Correspondence].

PMID- 29070346
TI  - In reply to 'Language in tuberculosis services' [Correspondence].

PMID- 29070365
TI  - Errata.
AB  - IN THE ARTICLE entitled 'Time to act to prevent and control tuberculosis among
      inmates' by M. Dara, S. S. Chadha, N. V. Melchers, J. van den Hombergh, E.
      Gurbanova, H. Al-Darraji, J. B. W. van der Meer (Int J Tuberc Lung Dis 2013;
      17(1): 4-5; http://dx.doi.org/10.5588/ijtld.12.0909), the name of author N. V.
      Melchers should have read N. V. S. Vinkeles Melchers, and her affiliation should
      have read: Academic Medical Center, Department of Global Health, University of
      Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, The
      Netherlands.

PMID- 29070366
TI  - Errata.
AB  - IN THE ARTICLE entitled 'Trends in the annual risk of tuberculous infection in
      India' by V. K. Chadha, R. Sarin, P. Narang, K. R. John, K. K. Chopra, R.
      Jitendra, D. K. Mendiratta, V. Vohra, A. N. Shashidhara, G. Muniraj, P. G. Gopi,
      P. Kumar (Int J Tuberc Lung Dis 2013; 17(3): 312-319;
      http://dx.doi.org/10.5588/ijtld.12.0330), the affiliation for G. Muniraj should
      have read Department of Community Medicine, Christian Medical College, Vellore,
      Tamil Nadu.

PMID- 29070367
TI  - Joseph Adera Odhiambo, 1954-2012 [Obituary].

PMID- 29070383
TI  - Erratum to 'An evaluation of "Ribolola": a household tuberculosis contact tracing
      programme in North West Province, South Africa'.
AB  - IN THE ARTICLE entitled 'An evaluation of "Ribolola": a household tuberculosis
      contact tracing programme in North West Province, South Africa' by Thind D,
      Charalambous S, Tongman A, Churchyard G, Grant AD (Int J Tuberc Lung Dis 2012;
      16(12): 1643-1648; http://dx.doi.org/10.5588/ijtld.12.0074), two errors
      occurred:On page 1644, paragraph 3, 'Those aged >5 years who were already on TBPT
      were nonetheless screened' should have read: 'Those aged >=5 years who were
      already on TBPT were nonetheless screened'.And on page 1645, paragraph 6, 'All
      were aged <5 years' should have read: 'All were aged 5 years'.

PMID- 29070389
TI  - In reply to 'Declaration on palliative care for MDR/XDR-TB' [Correspondence].

PMID- 29070408
TI  - Medicinal Chemistry.

PMID- 29070409
TI  - Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.
AB  - The marine environment harbors a vast number of species that are the source of a
      wide array of structurally diverse bioactive secondary metabolites. At this point
      in time, roughly 27'000 marine natural products are known, of which eight are
      (were) at the origin of seven marketed drugs, mostly for the treatment of cancer.
      The majority of these drugs and also of drug candidates currently undergoing
      clinical evaluation (excluding antibody-drug conjugates) are unmodified natural
      products, but synthetic chemistry has played a central role in the discovery
      and/or development of all but one of the approved marine-derived drugs. More than
      1000 new marine natural products have been isolated per year over the last
      decade, but the pool of new and unique structures is far from exhausted. To fully
      leverage the potential offered by the structural diversity of marine-produced
      secondary metabolites for drug discovery will require their broad assessment for
      different bioactivities and the productive interplay between new fermentation
      technologies, synthetic organic chemistry, and medicinal chemistry, in order to
      secure compound supply and enable lead optimization.

PMID- 29070410
TI  - Exploring Natural Product Fragments for Drug and Probe Discovery.
AB  - Fragment-based ligand discovery is a key technology to develop lead structures
      for drug discovery. The majority of the fragments employed so far is aromatic and
      sp2-configured, and there is a high demand of fragments with stereogenic centers.
      Natural products (NPs) are evolutionary selected ligands for a range of diverse
      macromolecular targets. Small-sized molecules - fragments - based on NPs may
      inherit the biological relevance of nature's treasure and could offer novel
      opportunities to engage challenging protein targets. An overview of this emerging
      research area is presented. The deconstruction of a complex NP into small
      fragments marks the beginning of this journey that is facilitated by the
      synthesis of NP-based 3D fragments. The emerging strategies in organic synthesis
      for either degradation of NPs to access fragments or de novo construction of
      fragments and their further combinations to chart novel biologically relevant
      chemical space is discussed.

PMID- 29070411
TI  - Chemical Space: Big Data Challenge for Molecular Diversity.
AB  - Chemical space describes all possible molecules as well as multi-dimensional
      conceptual spaces representing the structural diversity of these molecules. Part
      of this chemical space is available in public databases ranging from thousands to
      billions of compounds. Exploiting these databases for drug discovery represents a
      typical big data problem limited by computational power, data storage and data
      access capacity. Here we review recent developments of our laboratory, including
      progress in the chemical universe databases (GDB) and the fragment subset FDB-17,
      tools for ligand-based virtual screening by nearest neighbor searches, such as
      our multi-fingerprint browser for the ZINC database to select purchasable
      screening compounds, and their application to discover potent and selective
      inhibitors for calcium channel TRPV6 and Aurora A kinase, the polypharmacology
      browser (PPB) for predicting off-target effects, and finally interactive 3D
      chemical space visualization using our online tools WebDrugCS and WebMolCS. All
      resources described in this paper are available for public use at
      www.gdb.unibe.ch.

PMID- 29070412
TI  - The Screening Compound Collection: A Key Asset for Drug Discovery.
AB  - In this case study on an essential instrument of modern drug discovery, we
      summarize our successful efforts in the last four years toward enhancing the
      Actelion screening compound collection. A key organizational step was the
      establishment of the Compound Library Committee (CLC) in September 2013. This
      cross-functional team consisting of computational scientists, medicinal chemists
      and a biologist was endowed with a significant annual budget for regular new
      compound purchases. Based on an initial library analysis performed in 2013, the
      CLC developed a New Library Strategy. The established continuous library turn
      over mode, and the screening library size of 300'000 compounds were maintained,
      while the structural library quality was increased. This was achieved by shifting
      the selection criteria from 'druglike' to 'leadlike' structures, enriching for
      non-flat structures, aiming for compound novelty, and increasing the ratio of
      higher cost 'Premium Compounds'. Novel chemical space was gained by adding
      natural compounds, macrocycles, designed and focused libraries to the collection,
      and through mutual exchanges of proprietary compounds with agrochemical
      companies. A comparative analysis in 2016 provided evidence for the positive
      impact of these measures. Screening the improved library has provided several
      highly promising hits, including a macrocyclic compound, that are currently
      followed up in different Hit-to-Lead and Lead Optimization programs. It is
      important to state that the goal of the CLC was not to achieve higher HTS hit
      rates, but to increase the chances of identified hits to serve as the basis of
      successful early drug discovery programs. The experience gathered so far
      legitimates the New Library Strategy.

PMID- 29070413
TI  - Design, Properties and Recent Application of Macrocycles in Medicinal Chemistry.
AB  - Macrocyclic compounds have recently received increasing attention in drug
      discovery as these compounds offer the potential to modulate difficult targets
      and to access novel chemotypes. Approaches towards libraries of macrocyclic
      compounds based on modular organic synthesis and applications of these technology
      platforms to find and improve biologically active compounds are introduced in
      this minireview. Alternatively, lead compounds may be obtained by truncation and
      modification of macrocyclic natural products. Selected medicinal chemistry
      programs are discussed, illustrating a macrocyclization approach toward ligands
      with improved properties. The design of such ligands is often informed by X-ray
      crystal structures of protein-ligand complexes. Efforts to understand cellular
      permeability and oral bioavailability of cyclic peptides and non-peptidic
      macrocycles are summarized.

PMID- 29070414
TI  - Following the Lead from Nature with Covalent Inhibitors.
AB  - Covalent inhibitors are re-emerging as pharmacologically interesting entities
      with several candidates having received recent approval for therapeutic
      intervention. Nature has embraced this strategy and many natural products possess
      mildly electrophilic moieties able to covalently engage a target protein. This
      review surveys recent case studies for the identification of the target proteins
      of natural products. While sesquiterpene lactones represent a vast repertoire of
      covalent inhibitors, they can also be found in other classes of natural products,
      with sometimes unusual mechanisms to unmask the electrophilic moieties. These
      examples ought to be inspiring for the development of new biochemical probes and
      tomorrow's first-in-class drugs.

PMID- 29070416
TI  - Discovery of Potent and Selective p53-MDM2 Protein-Protein Interaction Inhibitors
      as Anticancer Drugs.
AB  - As a result of our persistent efforts to discover novel inhibitors of the p53
      MDM2 protein-protein interaction useful for the treatment of cancer, the potent
      and selective MDM2 inhibitors NVP-CGM097 and NVP-HDM201 with excellent in vitro
      and in vivo profile were selected as clinical candidates and are currently in
      phase 1 clinical development. This short review article provides a summary of the
      program history, the applied pharmacophore model and the discovery story of these
      novel p53-MDM2 inhibitor investigational drugs.

PMID- 29070415
TI  - Targeted Delivery of Cytotoxic Drugs: Challenges, Opportunities and New
      Developments.
AB  - Cytotoxic drugs, which are commonly used for the pharmacotherapy of many forms of
      cancer, often cause substantial toxicity to the patient without being able to
      induce long-lasting remissions. Ligands specific to accessible tumor-associated
      targets, capable of selective localization at the neoplastic site, may facilitate
      the preferential delivery of anti-cancer drugs, boosting activity and helping
      spare normal organs. In this article, we present a critical analysis of the
      limitation of conventional anti-cancer drugs and we contrast monoclonal
      antibodies and small organic ligands, as vehicles for pharmacodelivery
      applications.

PMID- 29070418
TI  - Top 200 Drugs by Worldwide Sales 2016.
AB  - The poster series of the Top 200 Drugs by Worldwide Sales by G. Sedelmeier and J.
      Sedelmeier has now been updated with an overview of the top selling drugs in
      2016. QuintilesIMS collected sales numbers in 59 countries for all companies.

PMID- 29070417
TI  - Milestones to the Discovery of T-type Calcium Channel Blockers for the Treatment
      of Generalized Epilepsies.
AB  - We describe the discovery and optimization of new, brain-penetrant T-type calcium
      channel blockers. We present optimized compounds with excellent efficacy in a
      rodent model of generalized absence-like epilepsy. Along the fine optimization of
      a chemical series with a pharmacological target located in the CNS (target
      potency, brain penetration, and solubility), we successfully identified an Ames
      negative aminopyrazole as putative metabolite of this compound series. Our
      efforts culminated in the selection of compound 20, which was elected as a
      preclinical candidate.

PMID- 29070423
TI  - BioTech 2017 Conference Report, Wadenswil, 7./8.9.2017.
AB  - Almost 200 scientists and professionals from academia and industry attended the
      BioTech 2017 conference at the Zurich University of Applied Sciences (ZHAW) in
      Wadenswil on 7./8. September 2017. The focus of this year's conference was (bio)
      process analytics and sensor technology, taking into account the increasingly
      prominent role of online measurement and control in the process industry.

PMID- 29070424
TI  - Markt, Apparate, Chemikalien, Firmenportraits und Dienstleistungen.

PMID- 29070422
TI  - Production of a Recombinant Catechol 2,3-Dioxygenase for the Degradation of
      Micropollutants.
AB  - Phenolic compounds such as catechol represent a particular type of micropollutant
      whose high stability prevents rapid decay and metabolization in the environment.
      We successfully cloned a catechol 2,3-dioxygenase (C2,3O) from Pseudomonas putida
      mt-2 and expressed it in Escherichia coli BER2566. The biomass isolated from
      shake-flask fermentations was used to partially purify the enzyme. The enzyme
      proved unstable in clarified liquid fractions (50 mM Tris buffer, pH 7.6) and
      lost more than 90% of its activity over 7 h at 25  degrees C. In the presence of
      10% acetone, the process was slowed down and 30% residual activity was still
      present after 7 h incubation. Storage of the enzyme in clear liquid fractions
      also proved difficult and total inactivation was achieved after 2 weeks even when
      kept frozen at -20  degrees C. Lowering the storage temperature to -80  degrees C
      preserved 30% activity over the same period. Only minor reactivation of the
      affected enzyme could be achieved after incubation at 20  degrees C in the
      presence of FeSO4 and/or ascorbic acid. Activity loss seems to be due mostly to
      Fe2+ oxidation as well as to subunit dissociation in the tetrameric structure.
      However, complete degradation of 1.0 mM catechol could be achieved at 20  degrees
      C and pH 7.6 over a 3 h period when using a suspension of whole cells or alginate
      encapsulated cells for the biotransformation. Contrary to the clear liquid
      fractions, these forms of biocatalyst showed no significant sign of inactivation
      under the working conditions.

PMID- 29070425
TI  - Towards Better Health.

PMID- 29070426
TI  - The Prevalence of Mental Illness in Homeless People in Germany.
AB  - BACKGROUND: The number of homeless people in Germany is increasing. Studies from
      multiple countries have shown that most homeless people suffer from mental
      illnesses that require treatment. Accurate figures on the prevalence of mental
      illness among the homeless in Germany can help improve care structures for this
      vulnerable group. METHODS: We carried out a systematic review and meta-analysis
      on the prevalence of mental illness among homeless people in Germany. RESULTS: 11
      pertinent studies published from 1995 to 2013 were identified. The overall study
      population consisted of 1220 homeless people. The pooled prevalence of axis I
      disorders was 77.4%, with a 95% confidence interval [95% CI] of [71.3; 82.9].
      Substance-related disorders were the most common type of disorder, with a pooled
      prevalence of 60.9% [53.1; 68.5]. The most common among these was alcoholism,
      with a prevalence of 55.4% [49.2; 61.5]. There was marked heterogeneity across
      studies. CONCLUSION: In Germany, the rate of mental illness requiring treatment
      is higher among the homeless than in the general population. The development and
      implementation of suitable care models for this marginalized and vulnerable group
      is essential if their elevated morbidity and mortality are to be reduced.

PMID- 29070428
TI  - Lemierre Syndrome After Tonsillectomy.

PMID- 29070427
TI  - The Medical Treatment of Homeless People.
AB  - BACKGROUND: The homeless are often in poor health, and their risk of premature
      death is three to four times that of the general population. This article is
      intended to provide an overview of the medical care of the homeless in Germany.
      METHODS: We selectively reviewed pertinent scientific and non-scientific
      publications from the years 2000-2017 that were retrieved from PubMed, from the
      reports of the German Homeless Aid Society (Bundesarbeitsgemeinschaft
      Wohnungslosenhilfe), from the websites of homeless aid organizations, and from
      Google Scholar. RESULTS: At least 75% of the homeless currently suffer from a
      mental illness requiring treatment. Common somatic problems include respiratory
      (6-14%) and cardiovascular disorders (7-20%), injuries and intoxications (5-15%),
      and infectious and parasitic diseases (10-16%). To circumvent the multiple
      barriers impeding homeless people's access to standard medical care (lack of
      health insurance, a feeling of being unwelcome, lack of disease awareness,
      impaired capacity for compliance), medical help is offered to them outside the
      system in a number of ways, embedded in an overall scheme of social and practical
      assistance with daily living. These medical resources differ from region to
      region. They are often underfinanced and tend to focus on acute general medical
      care, with limited access to specialists. CONCLUSION: More heath care resources
      need to be made available to the homeless beyond standard medical care. Concrete
      suggestions are discussed in the text.

PMID- 29070429
TI  - Decrease in Chronobiological Adaptability.

PMID- 29070430
TI  - In Reply.

PMID- 29070432
TI  - Corrigendum to "Prodepressant- and anxiogenic-like effects of serotonin
      selective, but not noradrenaline-selective, antidepressant agents in mice lacking
      alpha2-containing GABAA receptors" [Behav. Brain Res. 332 (2017) 172-179].

PMID- 29070431
TI  - Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)
      for disseminated intra-abdominal malignancies in children-a single-institution
      experience.
AB  - PURPOSE: Our purpose was to present our institutional experience with performing
      complete cytoreduction surgery and heated intraoperative chemotherapy (CRS-HIPEC)
      for children with disseminated intraabdominal malignancies, guided by a leading
      international center performing CRS-HIPEC in children. METHODS: Retrospective
      chart review of all cases of CRS-HIPEC in children in our institution, examining
      diagnosis, preoperative management, operative management, postoperative
      treatment, short term outcome including length of stay and complications, and
      long term outcome including survival and recurrence of disease. RESULTS: 9
      children underwent CRS-HIPEC over 48months. The mean age of the patients was
      8years. Tumors were: rhabdomyosarcoma (RMS), mesothelioma, Sertoli-Leydig,
      desmoplastic small round cell tumor, colon carcinoma and Wilms' tumor. Most
      patients received intraperitoneal cisplatin. Short term outcome was very good
      with median length of hospital stay of 13days and low rate of complications.
      Seven patients were alive at last follow up. Five patients developed a recurrent
      disease. Recurrence was intraabdominal in two of these patients. CONCLUSIONS: CRS
      HIPEC for children with disseminated intraabdominal malignancies performed in a
      dedicated institution and with guidance by a leading international center can be
      performed safely. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: IV.

PMID- 29070433
TI  - Knowledge and attitudes of paramedics toward the usage of capnography as a
      ventilation monitoring tool during resuscitation.

PMID- 29070434
TI  - Gerbil bite anaphylaxis.
AB  - Household pets are well known to cause allergic symptoms in susceptible
      individuals, most commonly conjunctivitis, rhinitis, bronchospasm or urticaria.
      The increasing prevalence of exotic pets, including rodents, may introduce novel
      allergens into the household setting. We describe the case of a 16-year-old
      female who presented to the emergency department (ED) with an immediate systemic
      reaction consistent with anaphylaxis following a bite injury from a pet Mongolian
      gerbil. Although rare, gerbil bite injury represents another possible allergen
      source for precipitating a severe allergic reaction.

PMID- 29070435
TI  - An analysis of factors affecting the accuracy of endoscopic biopsy after
      neoadjuvant chemoradiotherapy in patients with esophageal squamous cell
      carcinoma.
AB  - PURPOSE: The accuracy of endoscopic esophageal biopsy after neoadjuvant
      chemoradiotherapy (nCRT) remains suboptimal. We retrospectively examined the
      factors that may affect the diagnostic accuracy of post-nCRT endoscopic biopsy in
      patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A
      total of 213 ESCC patients were enrolled. Biopsy findings were cross-checked
      against the final pathology outcomes (ypT0 versus non-ypT0) to assess their
      accuracy. The independent predictors of diagnostic accuracy were identified by
      multivariate logistic regression analysis. RESULTS: Post-nCRT endoscopic biopsy
      results were diagnostically consistent with the final pathology outcomes in 116
      (54.5%) patients. Multivariate logistic regression analysis identified a long
      time interval between the completion of nCRT and the endoscopic examination as
      the only factor independently associated with a higher diagnostic accuracy.
      Receiver operating characteristic curve analysis showed that the optimal cutoff
      value for the time interval between nCRT completion and endoscopic biopsy was 45
      days. The estimated diagnostic accuracies of biopsies performed before and after
      the optimal cutoff time were 49.1% and 72.9%, respectively. CONCLUSIONS:
      Endoscopic biopsies performed >=45 days after nCRT are associated with a higher
      diagnostic accuracy. This time cutoff may serve as a reference to inform the
      choice of the optimal treatment strategy following nCRT, especially among
      complete responders in whom surgery withholding is being considered.

PMID- 29070436
TI  - Western diet increases cardiac ceramide content in healthy and hypertrophied
      hearts.
AB  - BACKGROUND AND AIMS: Obesity and cardiac left ventricular hypertrophy (LVH) are
      recognised independent risk factors in the development of heart failure (HF).
      However, the combination of these factors may exacerbate the onset of
      cardiovascular disease by mechanisms as yet unclear. LVH leads to significant
      cellular remodelling, including alterations in metabolism which may result in an
      inappropriate accumulation of lipids and eventual lipotoxicity and apoptosis. The
      aim of the study was to determine the impact of dietary manipulation on cardiac
      metabolism in the obese and hypertrophied heart. METHODS AND RESULTS: LVH was
      induced via aortic constriction (AC) in an experimental model of cardiac
      hypertrophy and animals subjected to 9 weeks of dietary manipulation with either
      a standard, high fat, or a sucrose containing Western-style diet (SD, HFD and WD,
      respectively). This latter diet resulted in accelerated weight gain in both
      LVH/AC and control animals. LVH was greater in AC animals fed a WD, and both
      control and AC animals from this diet showed a significant reduction in cardiac
      fatty acid oxidation and increased triacylglycerol content. Ceramide content was
      significantly increased in the WD groups, with no additional effect of LVH.
      Comparison with a model of HF induced by exposure to Doxorubicin and WD showed
      exacerbated remodelling of cardiac ceramide species leading to increased C16 and
      C18 content. CONCLUSIONS: These findings highlight the inappropriate accumulation
      and re-distribution of cardiac ceramide species in a diet-induced model of
      obesity and LVH, potentially increasing susceptibility to cell death. The
      combination of increased fat and sugar leads to greater pathological remodelling
      and may explain why this diet pattern is consistently linked with poor
      cardiovascular outcomes.

PMID- 29070437
TI  - Factors associated with diabetic nephropathy in children, adolescents, and adults
      with type 1 diabetes.
AB  - BACKBROUD/PURPOSE: Microalbuminuria and macroalbuminuria are markers of diabetic
      nephropathy (DN). The purpose of this study was to unravel the risk factors for
      DN in the young patients with type 1 diabetes (T1D). METHODS: 341 patients (160
      males) with T1D diagnosed at the age 7.6 +/- 4.0 years with disease duration 11.5
      +/- 6.5 years were assessed. Among them, 185 were young adults (aged 18.0-36.2
      years). Urinary albumin creatinine ratio (UACR) was checked on morning spot
      urine. Microalbuminuria and macroalbuminuria were defined as a UACR of 30-300
      mg/g and >300 mg/g, respectively, in at least 2 consecutive specimens. RESULTS:
      50 (14.7%) patients were classified as microalbuminuria and 13 (3.8%) as
      macroalbuminuria. In all patients, multivariate logistic regression revealed that
      the most significant risk factors were average HbA1c (%), OR (95% CI) = 1.76
      (1.37-2.25), P = 0.002); and male sex, OR = (odd ratio 2.31 (1.19-4.46), P =
      0.013). In adult patients, the most significant factors were average HbA1c, OR =
      1.74 (1.32-2.31), P = 0.003; and systolic blood pressure, OR = 1.06 (1.01-1.11),
      P = 0.011. Survival analysis showed average HbA1c levels significantly influenced
      the development of DN. CONCLUSION: The most important risk factors for DN were
      average HbA1c and age. When microalbuminuria is detected, proper treatment with
      ACEIs or ARBs and improving glycemic control can delay progression of DN.

PMID- 29070438
TI  - Humanin affects object recognition and gliosis in short-term cuprizone-treated
      mice.
AB  - Humanin (HN) is a 24-residue peptide that manipulates cell survival under various
      stresses. A highly potent HN derivative, HNG, reduced amyloid burden and
      neuroinflammation and suppressed cognitive impairment in Alzheimer's disease
      model mice. Cuprizone (CPZ), a copper chelator, provokes demyelination in the
      central nervous system of mice. A shorter (one week) exposure to CPZ induces
      schizophrenia-like behavior and glial activation prior to demyelination. We
      tested the effect of HNG on these short-term responses to CZP in mice.
      Intraperitoneal injection of HNG for one week improved object recognition memory
      but not working memory in CPZ-treated mice. Quantitative PCR analyses showed that
      HNG significantly suppressed CPZ-induced activation of microglia, but did not
      alter the reduced level of a myelin-specific transcript. These results suggest
      that HN can suppress neuroinflammation and the associated cognitive deficit in a
      wider range of neurological disorders beyond Alzheimer's disease.

PMID- 29070439
TI  - Amyloid and immune homeostasis.
AB  - Extracellular amyloid deposition defines a range of amyloidosis and amyloid
      related disease. Addition to primary and secondary amyloidosis, amyloid-related
      disease can be observed in different tissue/organ that sharing the common
      pathogenesis based on the formation of amyloid deposition. Currently, both
      Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only
      based on the autopsy results, by which amyloidosis of the associative
      tissue/organ is observed. Intriguingly, since it demonstrated that amyloid
      deposits trigger inflammatory reaction through the activation of cascaded immune
      response, wherein several lines of evidence implies a protective role of amyloid
      in preventing autoimmunity. Furthermore, attempts for preventing amyloid
      formation and/or removing amyloid deposits from the brain have caused
      meningoencephalitis and consequent deaths among the subjects. Hence, it is
      important to note that amyloid positively participates in maintaining immune
      homeostasis and contributes to irreversible inflammatory response. In this
      review, we will focus on the interactive relationship between amyloid and the
      immune system, discussing the potential functional roles of amyloid in immune
      tolerance and homeostasis.

PMID- 29070442
TI  - Social Recovery Therapy in improving activity and social outcomes in early
      psychosis: Current evidence and longer term outcomes.
AB  - BACKGROUND: Social Recovery Therapy (SRT) is a cognitive behavioural therapy
      which targets young people with early psychosis who have complex problems
      associated with severe social disability. This paper provides a narrative
      overview of current evidence for SRT and reports new data on a 2year follow-up of
      participants recruited into the Improving Social Recovery in Early Psychosis
      (ISREP) trial. METHOD: In the ISREP study 50 participants (86%) were followed up
      at 2years, 15months post treatment. The primary outcome was engagement in paid
      work, assessed using the Time Use Survey. Engagement in education and voluntary
      work were also assessed. In addition, the Positive and Negative Syndrome Scales
      (PANSS) and the Beck Hopelessness Scale (BHS) were administered. RESULTS: 25% of
      individuals with non-affective psychosis in the treatment group had engaged in
      paid work at some point in the year following the end of therapy, compared with
      none of the control group. Data from the PANSS and BHS suggested no worsening of
      symptoms and an indication that gains in hope were maintained over the 15month
      period following the end of therapy. CONCLUSION: Social Recovery Therapy is a
      promising psychological intervention which may improve social recovery in
      individuals with early psychosis. The new data reported in this paper shows
      evidence of gains in engagement in paid employment outcomes that persisted
      15months beyond the period of active intervention.

PMID- 29070441
TI  - Reduced auditory segmentation potentials in first-episode schizophrenia.
AB  - Auditory scene analysis (ASA) dysfunction is likely an important component of the
      symptomatology of schizophrenia. Auditory object segmentation, the grouping of
      sequential acoustic elements into temporally-distinct auditory objects, can be
      assessed with electroencephalography through measurement of the auditory
      segmentation potential (ASP). Further, N2 responses to the initial and final
      elements of auditory objects are enhanced relative to medial elements, which may
      indicate auditory object edge detection (initiation and termination). Both ASP
      and N2 modulation are impaired in long-term schizophrenia. To determine whether
      these deficits are present early in disease course, we compared ASP and N2
      modulation between individuals at their first episode of psychosis within the
      schizophrenia spectrum (FE, N=20) and matched healthy controls (N=24). The ASP
      was reduced by >40% in FE; however, N2 modulation was not statistically different
      from HC. This suggests that auditory segmentation (ASP) deficits exist at this
      early stage of schizophrenia, but auditory edge detection (N2 modulation) is
      relatively intact. In a subset of subjects for whom structural MRIs were
      available (N=14 per group), ASP sources were localized to midcingulate cortex
      (MCC) and temporal auditory cortex. Neurophysiological activity in FE was reduced
      in MCC, an area linked to aberrant perceptual organization, negative symptoms,
      and cognitive dysfunction in schizophrenia, but not temporal auditory cortex.
      This study supports the validity of the ASP for measurement of auditory object
      segmentation and suggests that the ASP may be useful as an early index of
      schizophrenia-related MCC dysfunction. Further, ASP deficits may serve as a
      viable biomarker of disease presence.

PMID- 29070443
TI  - Psychosocial factors associated with physical activity behavior among patients
      with psychosis.
AB  - INTRODUCTION: Although physical activity helps to improve functioning and reduce
      the symptoms of mental illness, physical inactivity remains common in the mental
      illness population. This study aims to explore the associations between
      theoretical constructs in relation to physical activity behavior based on
      psychological theories to examine reasons for physical inactivity in psychosis
      population. METHODS: One hundred and eighty one Chinese outpatients diagnosed
      with psychotic disorders were recruited for this cross-sectional study.
      Sociodemographic data and responses to questionnaires measuring self-efficacy,
      decisional balance, processes of change, and stages of change on physical
      activity habit were collected. RESULTS: Ninety three subjects (51.4%) had the
      intention to engage in regular physical activity within the next six months.
      Significant differences were found in self-efficacy, pros of decisional balance
      and processes of change across the stages of change. Moreover, overall
      classification accuracy was 60.8% across the stages of change. CONCLUSIONS: This
      study supports self-efficacy, pros of decisional balance and processes of change
      as useful factors in understanding physical activity behavior among patients with
      psychosis. Future promotions of regular physical activity can focus on improving
      self-efficacy, emphasizing on the benefits of regular physical activity and
      facilitating cognitive and behavior strategies from processes of change.

PMID- 29070444
TI  - Linking crop structure, throughfall, soil surface conditions, runoff and soil
      detachment: 10 land uses analyzed in Northern Laos.
AB  - In Montane Southeast Asia, deforestation and unsuitable combinations of crops and
      agricultural practices degrade soils at an unprecedented rate. Typically,
      smallholder farmers gain income from "available" land by replacing fallow or
      secondary forest by perennial crops. We aimed to understand how these practices
      increase or reduce soil erosion. Ten land uses were monitored in Northern Laos
      during the 2015 monsoon, using local farmers' fields. Experiments included plots
      of the conventional system (food crops and fallow), and land uses corresponding
      to new market opportunities (e.g. commercial tree plantations). Land uses were
      characterized by measuring plant cover and plant mean height per vegetation
      layer. Recorded meteorological variables included rainfall intensity, throughfall
      amount, throughfall kinetic energy (TKE), and raindrop size. Runoff coefficient,
      soil loss, and the percentage areas of soil surface types (free aggregates and
      gravel; crusts; macro-faunal, vegetal and pedestal features; plant litter) were
      derived from observations and measurements in 1-m2 micro-plots. Relationships
      between these variables were explored with multiple regression analyses. Our
      results indicate that TKE induces soil crusting and soil loss. By reducing
      rainfall infiltration, crusted area enhances runoff, which removes and transports
      soil particles detached by splash over non-crusted areas. TKE is lower under land
      uses reducing the velocity of raindrops and/or preventing an increase in their
      size. Optimal vegetation structures combine minimum height of the lowest layer
      (to reduce drop velocity at ground level) and maximum coverage (to intercept the
      largest amount of rainfall), as exemplified by broom grass (Thysanolaena
      latifolia). In contrast, high canopies with large leaves will increase TKE by
      enlarging raindrops, as exemplified by teak trees (Tectona grandis), unless a
      protective understorey exists under the trees. Policies that ban the burning of
      multi-layered vegetation structure under tree plantations should be enforced.
      Shade-tolerant shrubs and grasses with potential economic return could be
      promoted as understorey.

PMID- 29070445
TI  - Dung beetles as drivers of ecosystem multifunctionality: Are response and effect
      traits interwoven?
AB  - Rapid biodiversity loss has emphasized the need to understand how biodiversity
      affects the provisioning of ecological functions. Of particular interest are
      species and communities with versatile impacts on multiple parts of the
      environment, linking processes in the biosphere, lithosphere, and atmosphere to
      human interests in the anthroposphere (in this case, cattle farming). In this
      study, we examine the role of a specific group of insects - beetles feeding on
      cattle dung - on multiple ecological functions spanning these spheres (dung
      removal, soil nutrient content and greenhouse gas emissions). We ask whether the
      same traits which make species prone to extinction (i.e. response traits) may
      also affect their functional efficiency (as effect traits). To establish the link
      between response and effect traits, we first evaluated whether two traits (body
      mass and nesting strategy, the latter categorized as tunnelers or dwellers)
      affected the probability of a species being threatened. We then tested for a
      relationship between these traits and ecosystem functioning. Across Scandinavian
      dung beetle species, 75% of tunnelers and 30% of dwellers are classified as
      threatened. Hence, nesting strategy significantly affects the probability of a
      species being threatened, and constitutes a response trait. Effect traits varied
      with the ecological function investigated: density-specific dung removal was
      influenced by both nesting strategy and body mass, whereas methane emissions
      varied with body mass and nutrient recycling with nesting strategy. Our findings
      suggest that among Scandinavian dung beetles, nesting strategy is both a response
      and an effect trait, with tunnelers being more efficient in providing several
      ecological functions and also being more sensitive to extinction. Consequently,
      functionally important tunneler species have suffered disproportionate declines,
      and species not threatened today may be at risk of becoming so in the near
      future. This linkage between effect and response traits aggravates the
      consequences of ongoing biodiversity loss.

PMID- 29070446
TI  - Microbial degradation of fomesafen and detoxification of fomesafen-contaminated
      soil by the newly isolated strain Bacillus sp. FE-1 via a proposed biochemical
      degradation pathway.
AB  - Fomesafen is a long residual herbicide and poses a potential risk to
      environmental safety, leading to an increasing need to find eco-friendly and cost
      effective techniques to remediate fomesafen-contaminated soils. In this article,
      a novel strain of Bacillus sp., FE-1 was isolated from paddy field soil. This
      strain was found to degrade fomesafen both in liquid medium and in soil. >82.9%
      of fomesafen, at concentrations of 0.5, 1 and 10mgL-1, was degraded by Bacillus
      sp. FE-1 in liquid medium within 14h. The optimal pH and temperature for
      degradation were 7.0 and 35 degrees C, respectively. Soil samples inoculated with
      strain FE-1 showed significantly increased rates of fomesafen degradation. Two
      metabolites of fomesafen degradation were detected and identified as amino
      fomesafen and 5-[2-chloro-4-(trifluoromethyl) phenoxy]-2-amino-benzoic acid. This
      is the first report of a novel fomesafen biodegradation pathway involving the
      reduction of a nitro group followed by the hydrolysis of an amide bond. The
      excellent remediation capability of the isolate FE-1 to detoxify fomesafen
      contaminated soil was shown by bioassay of the sensitive aftercrop corn. The
      results indicate that Bacillus sp. FE-1 has potential for use in the
      bioremediation of fomesafen-contaminated soil.

PMID- 29070447
TI  - Estimation model for evaporative emissions from gasoline vehicles based on
      thermodynamics.
AB  - In this study, we conducted seven-day diurnal breathing loss (DBL) tests on
      gasoline vehicles. We propose a model based on the theory of thermodynamics that
      can represent the experimental results of the current and previous studies. The
      experiments were performed using 14 physical parameters to determine the
      dependence of total emissions on temperature, fuel tank fill, and fuel vapor
      pressure. In most cases, total emissions after an apparent breakthrough were
      proportional to the difference between minimum and maximum environmental
      temperatures during the day, fuel tank empty space, and fuel vapor pressure.
      Volatile organic compounds (VOCs) were measured using a Gas Chromatography Mass
      Spectrometer and Flame Ionization Detector (GC-MS/FID) to determine the Ozone
      Formation Potential (OFP) of after-breakthrough gas emitted to the atmosphere.
      Using the experimental results, we constructed a thermodynamic model for
      estimating the amount of evaporative emissions after a fully saturated canister
      breakthrough occurred, and a comparison between the thermodynamic model and
      previous models was made. Finally, the total annual evaporative emissions and OFP
      in Japan were determined and compared by each model.

PMID- 29070440
TI  - Sensorimotor gating deficits in "two-hit" models of schizophrenia risk factors.
AB  - Genetic and environmental models of neuropsychiatric disease have grown
      exponentially over the last 20years. One measure that is often used to evaluate
      the translational relevance of these models to human neuropsychiatric disease is
      prepulse inhibition of startle (PPI), an operational measure of sensorimotor
      gating. Deficient PPI characterizes several neuropsychiatric disorders but has
      been most extensively studied in schizophrenia. It has become a useful tool in
      translational neuropharmacological and molecular genetics studies because it can
      be measured across species using almost the same experimental parameters.
      Although initial studies of PPI in rodents were pharmacological because of the
      robust predictive validity of PPI for antipsychotic efficacy, more recently, PPI
      has become standard common behavioral measures used in genetic and
      neurodevelopmental models of schizophrenia. Here we review "two hit" models of
      schizophrenia and discuss the utility of PPI as a tool in phenotyping these
      models of relevant risk factors. In the review, we consider approaches to rodent
      models of genetic and neurodevelopmental risk factors and selectively review "two
      hit" models of gene*environment and environment*environment interactions in which
      PPI has been measured.

PMID- 29070448
TI  - Exposure to the herbicide 2,4-D produces different toxic effects in two different
      phytoplankters: A green microalga (Ankistrodesmus falcatus) and a toxigenic
      cyanobacterium (Microcystis aeruginosa).
AB  - The extensive use of 2,4-dichlorophenoxiacetic acid (2,4-D) in agriculture is an
      important source of pollution to water and soil. Toxicity of commonly used
      herbicides to non-target, planktonic photosynthetic organisms has not been
      described completely yet. Therefore, we determined the effect of subinhibitory
      2,4-D concentrations on the Chlorophycean alga Ankistrodesmus falcatus and on a
      toxigenic strain of the cyanobacterium Microcystis aeruginosa. Population growth,
      photosynthetic pigments, macromolecular biomarkers (carbohydrates, lipids, and
      protein), and antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPx],
      and superoxide dismutase [SOD]) were quantified, and the integrated biomarker
      response (IBR) was calculated. Scanning electron microscope (SEM) and
      transmission electron microscope (TEM) observations were also performed. The 96-h
      median inhibitory concentration (IC50) for 2,4-D was 1353.80 and 71.20mgL-1 for
      the alga and the cyanobacterium, respectively. Under 2,4-D stress, both organisms
      increased pigments and macromolecules concentration, modified the activity of all
      the evaluated enzymes, and exhibited ultrastructural alterations. M. aeruginosa
      also increased microcystins production, and A. falcatus showed external
      morphological alterations. The green alga was tolerant to high concentrations of
      the herbicide, whereas the cyanobacterium exhibited sensitivity comparable to
      other phytoplankters. Both organisms were tolerant to comparatively high
      concentrations of the herbicide; however, negative effects on the assessed
      biomarkers and cell morphology were significant. Moreover, stimulation of the
      production of cyanotoxins under chemical stress could increase the risk for the
      biota in aquatic environments, related to herbicides pollution in eutrophic
      freshwater ecosystems.

PMID- 29070449
TI  - Assessing cover crop management under actual and climate change conditions.
AB  - The termination date is recognized as a key management factor to enhance cover
      crops for multiple benefits and to avoid competition with the following cash
      crop. However, the optimum date depends on annual meteorological conditions, and
      climate variability induces uncertainty in a decision that needs to be taken
      every year. One of the most important cover crop benefits is reducing nitrate
      leaching, a major concern for irrigated agricultural systems and highly affected
      by the termination date. This study aimed to determine the effects of cover crops
      and their termination date on the water and N balances of an irrigated
      Mediterranean agroecosystem under present and future climate conditions. For that
      purpose, two field experiments were used for inverse calibration and validation
      of the WAVE model (Water and Agrochemicals in the soil and Vadose Environment),
      based on continuous soil water content data, soil nitrogen content and crop
      measurements. The calibrated and validated model was subsequently used in
      advanced scenario analysis under present and climate change conditions. Under
      present conditions, a late termination date increased cover crop biomass and
      subsequently soil water and N depletion. Hence, preemptive competition risk with
      the main crop was enhanced, but a reduction of nitrate leaching also occurred.
      The hypothetical planting date of the following cash crop was also an important
      tool to reduce preemptive competition. Under climate change conditions, the
      simulations showed that the termination date will be even more important to
      reduce preemptive competition and nitrate leaching.

PMID- 29070450
TI  - Shading and sediment structure effects on stream metabolism resistance and
      resilience to infrequent droughts.
AB  - Perennial, temperate, low-order streams are predicted to become intermittent as a
      result of irregular droughts caused by global warming and increased water demand.
      We hypothesize that stream metabolism changes caused by irregular droughts are
      linked to the shading and bed sediment structure of temperate streams. We set up
      16 outdoor experimental streams with low or high shade conditions and streambeds
      either with alternating sorted patches of gravel and sand or homogeneous gravel
      sand mix sediment structures. We assessed community respiration (CR), net
      ecosystem production (NEP) and periphyton biomass and structure (diatoms, green
      algae, cyanobacteria) in the course of 6weeks colonization, 6weeks desiccation,
      and 2.5weeks after rewetting. The heterotroph to autotroph (H:A) and fungi to
      bacteria (F:B) ratios in the microbial biofilm community were assessed at the end
      of the colonization and rewetting phases. Streams with different bed sediment
      structure were functionally similar; their metabolism under desiccation was
      controlled solely by light availability. During flow recession, all streams
      showed net heterotrophy. As desiccation progressed, NEP and CR decreased to zero.
      Desiccation altered the periphyton composition from predominantly diatoms to
      green algae and cyanobacteria, particularly in streams with low shade and mixed
      sediments. Rapid post-drought resilience of NEP was accompanied by high
      cyanobacteria and green algae growth in low shade, but poor total periphyton
      growth in high shade streams. Variable periphyton recovery was followed by
      increased H:A in relation to shading, and decreased F:B in relation to sediments
      structure. These shifts resulted in poor CR recovery compared to the colonization
      phase, suggesting a link between CR resilience and microbial composition changes.
      The links between drought effects, post-drought recovery, shading level, and
      streambed structure reveal the importance of low-order stream management under a
      changing climate and land use to mitigate the future impact of unpredictable
      infrequent droughts on stream metabolism in temperate ecosystems.

PMID- 29070451
TI  - Arctic antibiotic resistance gene contamination, a result of anthropogenic
      activities and natural origin.
AB  - The increasing global prevalence of antibiotic resistance genes (ARGs) in the
      environment is attributed to anthropogenic activities, particularly the misuse of
      antimicrobial drugs in human care and animal production. In the present study, we
      first examined Arctic/sub-Arctic (polar) sediments for the abundance and
      diversity of 30 ARGs against sulfonamide, tetracycline, aminoglycoside,
      quinolone, macrolide, and beta-lactam antibiotics. Polar sediment ARGs were
      detected by qPCR at relatively low levels (10-9 to 10-5 copies/16S rRNA gene
      copies) compared to the reference sites, which were heavily impacted regions of
      China (the Haihe River, the Tianjin Water Park water and the Qilihai Wetland
      water, at 10-8 to 10-2 copies/16S rRNA gene copies). A human mitochondrial gene
      target, Hmt, was first used to aid in the identification of ARGs associated with
      anthropogenic activities, being relatively persistent, in high copy number and a
      human-specific molecular marker. Hmt was consistently present in easily
      quantifiable amounts in the polar sediment samples, indicating their relationship
      with human-impact, and it was also positively correlated with the relative
      abundance of ARGs and to the concentrations of modern-day antibiotics.
      Phylogenetic analyses of resistance sequences from both the Arctic marine
      sediments and a major database of human pathogens indicated that the ARGs in
      polar region were the result of a mix of human influence and natural origins. To
      our knowledge, this is the first study to show that ARGs in Arctic marine
      sediments appear to be a mixture of both natural origins and recent human
      influence. This study provides a significant reference regarding the global reach
      of antibiotic resistance, which is associated with anthropogenic activities.

PMID- 29070452
TI  - Physicochemical risk factors for building-related symptoms in air-conditioned
      office buildings: Ambient particles and combined exposure to indoor air
      pollutants.
AB  - We conducted a cross-sectional epidemiological study to examine the correlation
      between indoor air quality (IAQ) and building-related symptoms (BRSs) of office
      workers in air-conditioned office buildings. We investigated 11 offices during
      winter and 13 offices during summer in 17 buildings with air-conditioning systems
      in Tokyo, Osaka, and Fukuoka, and we included 107 office workers during winter
      and 207 office workers during summer. We conducted environmental sampling for
      evaluating IAQ and concurrently administered self-reported questionnaires to
      collect information regarding work-related symptoms. Multivariate analyses
      revealed that upper respiratory symptoms showed a significant correlation with
      increased indoor temperature [odds ratio (OR), 1.55; 95% confidence interval
      (CI), 1.11-2.18] and increased indoor concentration of suspended particles
      released from the ambient air pollution via air-conditioning systems (OR, 1.31;
      95% CI, 1.08-1.59) during winter. In particular, smaller particles (particle
      size>0.3MUm), which possibly penetrated through the filter media in air
      conditioning systems from ambient air, were correlated with upper respiratory
      symptoms. The use of high-efficiency particulate air filters in air-conditioning
      systems and their adequate maintenance may be an urgent solution for reducing the
      indoor air concentration of submicron particles. Several irritating volatile
      organic compounds (VOCs) (e.g., formaldehyde, acetaldehyde, ethylbenzene,
      toluene, and xylenes) that were positively correlated with the indoor air
      concentration among their VOCs, were associated with upper respiratory symptoms,
      although their indoor air concentrations were lower than those specified by the
      indoor air quality guideline. A new approach and strategy for decreasing the
      potential combined health risks (i.e., additive effect of risks) associated with
      multiple low-level indoor pollutants that have similar hazardous properties are
      required.

PMID- 29070453
TI  - Influence of dissolved organic matter on sorption and desorption of MCPA in
      ferralsol.
AB  - MCPA (4-chloro-2-methylphenoxyacetic acid) is an acidic herbicide, widely used in
      paddy fields. The presence of dissolved organic matter (DOM) modifies the
      sorption-desorption of herbicides in soils. In this study, effects of DOM on
      sorption- desorption of MCPA were tested using three typical ferralsol soil types
      from China: rhodic ferralsol, haplic ferralsol and paddy soil. DOM preparations
      were extracted from the paddy soil (DOMP), from a compost mixture of cassava
      stems with chicken manure (DOMC), and from rice straw (DOMR). Sorption-desorption
      of MCPA in the tested soil types was shown to follow pseudo first-order kinetics,
      and the calculated isotherm data fitted well with a Freundlich equilibrium model
      in the range of the studied concentrations. MCPA was weakly sorbed by the soils,
      producing low Freundlich coefficient values (Kf) (0.854 to 4.237). The presence
      of DOM reduced the Kf whereby DOMC had the strongest and DOMR the weakest effect.
      Presence of DOM also promoted MCPA desorption from the soils, again with DOMC
      having the strongest effect and DOMR the weakest. DOM coating changed the soil
      particle surface, as demonstrated by electron microscopy, and DOM also directly
      interacted with MCPA, as shown by Fourier-transform infrared spectroscopy. The
      experimental data were interpreted to suggest a competing sorption of DOM to
      ferralsol and an increased solubility of MCPA in the presence of DOM. The results
      indicate that the environmental risk of MCPA leaching to groundwater and surface
      flow is increased by presence of DOM, for instance as a result of organic
      fertilizer use.

PMID- 29070454
TI  - High levels of migratable lead and cadmium on decorated drinking glassware.
AB  - Externally decorated glassware used for the consumption of beverages, purchased
      new or sourced second-hand, and including tumblers, beer glasses, shot glasses,
      wine glasses and jars, has been analysed for Pb and Cd by portable x-ray
      fluorescence (XRF) spectrometry. Out of 197 analyses performed on distinctly
      different colours and regions of enamelling on 72 products, Pb was detected in
      139 cases and among all colours tested, with concentrations ranging from about 40
      to 400,000MUgg-1 (median=63,000MUgg-1); Cd was detected in 134 cases and among
      all colours apart from gold leaf, with concentrations ranging from about 300 to
      70,000MUgg-1 (median=8460MUgg-1). The frequent occurrence of these metals is
      attributed to their use in both the oxidic fluxes and coloured pigments of
      decorative enamels employed by the glass industry. A standard test involving
      extraction of the external surface to within 20mm of the rim (lip area) by 4%
      acetic acid and subsequent analysis by ICP was applied to selected positive
      samples (n=14). Lead concentrations normalised to internal volume exceeded limit
      values of 0.5mgL-1 in all but one case, with concentrations over 100mgL-1
      returned by three products. Cadmium concentrations exceeded limit values of 4mgL
      1 in five cases, with a maximum concentration of about 40mgL-1. Repeating the
      experiment on five positive samples using a carbonated drink (Coca Cola Classic)
      resulted in lower extractable concentrations but non-compliance for Pb in all
      cases. The presence of high concentrations of total and extractable Pb and Cd in
      the decorated lip areas of a wide range of products manufactured in both China
      and Europe is cause for concern from a health and safety perspective.

PMID- 29070455
TI  - [Efficacy of internalized RGD-modified echogenic liposomes in diagnosis and
      treatment in a mouse model of rheumatoid arthritis].
AB  - OBJECTIVE: To prepare internalized RGD (iRGD) modified echogenic liposomes
      containing methotrexate (MTX) and indocyanine green (ICG) (iRGD MTX ICG ELIP) and
      evaluate its targeting efficiency and inhibitory effect combined with ultrasound
      on synovial cells. METHODS: iRGD MTX ICG ELIP was prepared by the thin film
      rehydration and freeze-lyophilization method and its general characteristics and
      acoustic responsiveness were assessed. The targeting effect of the prepared
      liposome was observed by assessing its cell uptake in vitro. In a mouse model of
      rheumatiod arthritis, the targeting effect of the prepared liposome was
      determined by detecting the fluorescence intensity of the drug in arthrosis. The
      inhibitory effect of iRGD MTX ICG ELIP combined with ultrasound on synovial MH7A
      cells in vitro were investigated using CCK8 test. RESULTS: The average diameter
      and zeta potential of iRGD MTX ICG ELIP was 134.4?17.61 nm and 10.07?4.28 mV, and
      the entrapment efficiency of MTX and ICG was (62.56?0.77)% and (95.13?0.82)%,
      respectively. With ultrasound exposure, the release of MTX and ICG from iRGD MTX
      ICG ELIP increased with the ultrasound intensity and with the exposure time. In
      HUVECs, the uptake efficiency of iRGD MTX ICG ELIP was 1.89 times higher than
      that of non targeted MTX ICG ELIP (P<0.05). In vivo imaging of mouse joint with
      rheumatiod arthritis showed that the fluorescence intensity of iRGD MTX ICG ELIP
      was significantly stronger than that of the non targeted liposome. CCK8 assay
      showed that iRGD MTX ICG ELIP combined with ultrasound resulted in a survival
      rate of MH7A cells of (32.49?3.04)%, significantly lower than the rate of cells
      treated with iRGD MTX ICG ELIP but without ultrasound (P<0.05). CONCLUSIONS: iRGD
      MTX ICG ELIP has a suitable particle size and can effectively target HUVECs and
      the joints with rheumatiod arthritis. With a good drug entrapment efficiency and
      acoustic responsiveness, the drug loaded liposome shows enhanced inhibitory
      effect on MH7A cells combined with ultrasound in vitro, suggesting its potential
      in the treatment of rheumatoid arthritis.

PMID- 29070456
TI  - [Characterization of chromate resistance in genetically engineered Escherichia
      coli expressing chromate ion transporter ChrA].
AB  - OBJECTIVE: To construct a genetically engineered Escherichia coli expressing
      chromate (Cr) ion transporter ChrA and test its Cr resistance capacity. METHODS:
      ChrA gene was cloned by PCR from the DNA template of Serratia sp. S2 and linked
      with the prokaryotic vector pET-28a (+). The recombinant vector was transformed
      into E.coli BL21 (DE3) cells for expression of ChrA protein. Cr (VI) risistance
      and Cr (VI) uptake and efflux of the engineered bacteria were tested, and the
      effects of Cr loading time, oxyanions (ulfate, molybdate, vanadate, tungstate),
      and respiratory inhibitors (valinomycin, CN-, oligomycin, and NADH) on Cr (VI)
      efflux were examined to analyze the pathway of Cr (VI) transport by ChrA protein.
      RESULTS: The engineered E. coil strain was successfully constructed. Experiments
      using cell suspensions showed a lowered Cr2O72- uptake but an increased efflux
      capacity of ChrA-engineered bacteria compared with the control strain (P<0.05).
      The engineered E. coil cells in exponential growth incubated for 30 min in the
      presence of 50 mg/L Cr2O72- showed a total displacement of Cr (VI) of 20% after
      resuspension in PBS at 10 min, but chromate efflux decreased subsequently as the
      incubation time extended. Oxyanions sulfate and molybdate significantly inhibited
      chromate efflux in the engineered bacteria (P<0.05), whereas tungstate and
      vanadate did not obviously affect chromate efflux; chromate efflux was
      significantly inhibited by K+ ionophore valinomycin and CN-, enhanced by NADH
      (P<0.05), but not affected by oligomycin, suggesting the role of chromate
      transporter ChrA as a chemiosmotic pump that extrudes chromate using the proton
      motive force. CONCLUSION: ChrA can efficiently transport chromate ions from the
      cytoplasm to enhance chromate resistance of the genetically engineered E. coli.

PMID- 29070457
TI  - [Robotic surgery versus conventional open chest surgery for heart tumor: a
      propensity score matching analysis].
AB  - OBJECTIVE: To compare conventional open chest surgery and robotic surgery for
      their efficacy, short?term outcomes and patient selection in the treatment of
      heart tumors. Method The clinical data were collected from 225 patients (a total
      of 228 operations) who underwent cardiac neoplasm resection in our hospital
      between January, 1993 and April, 2016. A propensity score matching (PSM) was
      established according to the vital baseline data of the patients receiving
      conventional open chest surgery (n=125) and robotic surgery (n=60) after
      screening. The patients were matched for propensity into 60 pairs, and the
      efficacy, short?term outcomes and patient selection were compared between the two
      groups. RESULTS: Before PSM, the patients in conventional surgery group had
      significantly greater tumor size (P<0.001) and a higher proportion of patients
      with New York Heart Association functional class III and IV (P<0.001). The
      patients' baseline data were nearly balanced (P=0.982) between the two groups
      after matching. No significant differences were found between the two groups in
      cardiopulmonary bypass time (P=0.256), crossclamp time (P=0.862), in?hospital
      mortality (P=1.000), arrhythmia (P=1.000), delayed mechanical ventilation (>24 h;
      P=0.209), thoracic complications (P=0.611) or systemic embolism (P=1.000). The
      survival rates were 100% in both groups in the 6?month follow?up after the
      operation, and no significant difference was found between the two groups in the
      incidence of major adverse cardiac and cerebrovascular events within 6 months
      (P=0.438). CONCLUSION: Robotic heart tumor resection has a favorable efficacy
      with a good short?term prognosis, and can serve as an alternative for treatment
      of solitary lesions in low?risk patients receiving operations for the first time.

PMID- 29070458
TI  - [Receptor for advanced glycation end products upregulates MUC5AC expression and
      promotes mucus overproduction in mice with toluene diisocyanate-induced asthma].
AB  - OBJECTIVE: To explore the role of the receptor for advanced glycation end
      products (RAGE) in regulating the expression of MUC5AC and mucus production in a
      mouse model of toluene diisocyanate (TDI)?induced asthma. METHODS: BALB/c mice
      were randomly divided into control group, vehicle (AOO) group, TDI?induced asthma
      group and RAGE inhibitor (FPS?ZM1) group. PAS staining, Western blotting, and
      immunohistochemistry were used to analyze the changes in mucus production and
      MUC5AC expression in the airway of the mice, and the expression of p?ERK was
      detected with Western blotting. In vitro cultured human bronchial epithelial cell
      line 16HBE was transfected with lentiviral vector carrying short hairpin RNA
      targeting RAGE (shRNA?RAGE) and subsequently challenged with a TDI?human serum
      albumin (TDI-HSA) conjugate, and the changes in cellular MUC5AC mRNA expression
      as detected using RT-PCR; the protein expressions of ERK and p?ERK in the cells
      were examined with Western blotting. The effect of ERK inhibitor U0126
      pretreatment on MUC5AC mRNA expression was also analyzed in the cells. RESULTS:
      Compared with the control mice, TDI-induced asthmatic mice showed significantly
      higher rates of PAS positivity and increased MUC5AC and p?ERK expressions in the
      airway (P<0.05). Treatment with FPS?ZM1 significantly decreased PAS positivity
      and lowered MUC5AC and p?ERK expressions in the airway of the asthmatic mice
      (P<0.05). Exposure of 16HBE cells to TDI?HSA caused a significant increase in
      MUC5AC mRNA expression and p?ERK protein expression (P<0.05), while RAGE
      knockdown obviously suppressed TDI?HSA-induced upregulation of p-ERK and MUC5AC
      mRNA (P<0.05). Treatment with the ERK inhibitor U0126 also lowered
      TDI?HSA?induced up?regulation of MUC5AC mRNA in the cells (P<0.05). CONCLUSION:
      RAGE signaling induces MUC5AC expression via extracellular signal-regulated
      kinase pathway to promote mucus overproduction in mice with TDI-induced asthma.

PMID- 29070459
TI  - [Neutrophil to lymphocyte ratio as a predictor for type 2 diabetes mellitus in
      patients with chronic obstructive pulmonary disease: a cohort study of 404
      cases].
AB  - OBJECTIVE: To assess the value of neutrophil?to?lymphocyte ratio (NLR) for
      predicting type 2 diabetes mellitus (T2DM) in patients with chronic obstructive
      pulmonary disease (COPD). METHODS: A cohort of 404 non?diabetic patients
      diagnosed with stable COPD between January, 2010 and December, 2012 at Zhujiang
      Hospital were enrolled and followed up for 3 years, during which fast blood
      glucose (FBG) was monitored every 6 months. The primary endpoint was the
      occurrence of T2DM, and the cumulative incidence of T2DM in this cohort was
      calculated. The patients who developed T2DM and those without T2DM at the end of
      the follow?up were compared for clinical parameters to identify the potential
      predictors for T2DM in patients with stable COPD. RESULTS: After follow?up for a
      mean of 2.1 years, 41 (10.1%) patients with COPD developed T2DM, who showed
      significantly higher baseline NLR levels than those without T2DM (P<0.001). The
      receiver?operating characteristic (ROC) analysis revealed that the optimum
      cut?off value for NLR was 5.626. Spearman rank correlation analysis suggested
      that the incidence of T2DM in the patients was positively correlated with the
      number of hospital admissions for acute exacerbation of COPD in the past year
      (r=0.136, P=0.006), hypertension (r=0.151, P=0.002) and NLR (r=0.340, P<0.001).
      Logistic regression analysis identified triglyceride (TG) (P=0.047) and NLR
      (P<0.001) as the independent risk factors for T2DM in patients with COPD.
      CONCLUSION: The occurrence of T2DM in COPD patients is closely related to NLR
      level, which may serve as an early predictor for T2DM in these patients.

PMID- 29070460
TI  - [One-hour post-load plasma glucose: a better indicator of glucose metabolism for
      obstructive sleep apnea?]
AB  - OBJECTIVE: To assess the value of blood glucose at different time points in oral
      glucose tolerance test (OGTT), particularly one?hour post load plasma glucose (1
      hPG), in evaluating glucose metabolism in adult patients with obstructive sleep
      apnea (OSA). METHODS: Eighty nine adultswith newly diagnosed OSA were analyzed
      retrospectively for sleep architecture assessed using polysomnography and glucose
      metabolism assessed by OGTT at different time points (0, 30, 60, 120, and 180
      min). Pearson's correlatives and multiple linear regression models were
      established to investigate the correlations between glucose metabolism and other
      indices including sleep architecture, apnea hypopnea index (AHI), mean and lowest
      oxygen saturation (MSO2 and LSO2) and obesity measurements. RESULTS: The majority
      (67.4%) of the patients had abnormal 1 hPG, and 41.6% had abnormal 2 hPG. 1 hPG
      was positively correlated with neck circumference (r=0.245), abdomen
      circumference (r=0.231), systolic blood pressure (r=0.213), diastolic blood
      pressure (r=0.276) and AHI (r=0.324), and was negatively associated with MSO2 (r=
      0.341) and LSO2 (r=-0.387) (all P<0.05). After controlling for age, BMI, neck and
      abdomen circumferences, 1 hPG was found to inversely correlated with MSO2 (r=
      0.253, P=0.032) and LSO2 (r=-0.311, P=0.008). In non-obese OSA subgroup, 1 hPG
      was significantly associated with OSA-related indices, and regression models
      showed that LSO2 and N2 were the two most important contributors to 1 hPG
      (adjusted R2=0.349, P<0.001); plasma glucose at other time points did not show
      such correlations. CONCLUSIONS: 1 hPG abnormality occurs earlier than 2 hPG in
      OSA patients. 1 hPG is significantly associated with OSA independent of obesity
      and may serve as a better index for measuring OSA-related glucose disorder.

PMID- 29070461
TI  - [Rictor/mTORC2 regulates blood-testis barrier and spermatogenesis in mice].
AB  - OBJECTIVE: To investigate the role of Rictor/mTORC2 in the formation of blood
      testis barrier (BTB), testicular development, and spermatogenesis. METHODS: Amh
      Cre positive mice homozygous for rictor loxP with Sertoli cell specific deletion
      of rictor were obtained by cross breeding Amh Cre mice with rictor loxP mice. The
      histology of the reproductive organs, seminiferous tubules and epididymis of the
      transgenic mice was observed with HE staining. The cell subgroups of the germ
      cells in the seminiferous tubule were detected by flow cytometry with propidium
      iodide labeling. The expression levels of Ki 67 and separase were detected with
      immunofluorescence assay, and the expression levels of BTB associated proteins
      were detected with immunofluorescence and Western blotting. RESULTS: Compared
      with the control (Amh Cre-, rictorloxP/loxP or rictorloxP/-) mice, the mice with
      Sertoli cell specific rictor deletion showed significantly decreased testicular
      weight and epididymis weight (P<0.05), significantly increased diploid cells
      (P<0.01), and decreased haploid cells (P<0.01) but comparable tetraploid cells
      and similar expression levels of Ki 67 and separase. The mice with rictor
      knockout also showed aberrant localization of BTB associated proteins, which were
      scattered over the whole seminiferous epithelium, but the expression levels of
      the protein remained stable. CONCLUSION: Rictor in testicular Sertoli cells is
      essential for maintaining BTB integrity and function and ensuring normal
      spermatogenesis in mice.

PMID- 29070462
TI  - [Role of aquaporin-5 in regulating colorectal cancer cell growth in vitro].
AB  - OBJECTIVE: To study the role of aquaporin 5(AQP5) in regulating the cell
      proliferation and apoptosis of human colorectal cancer cells and explore the
      possible mechanism. METHODS: A small interfering RNA (siRNA) targeting AQP5 was
      used to suppress endogenous AQP5 expression in the human colorectal cancer cell
      lines COLO 205 and SW480, and the transfection efficiency of AQP5 siRNA was
      determined using immunofluorescence assay and PCR. The changes in the
      proliferation of the transfected cells was evaluated with MTT assay, and the cell
      apoptosis was analyzed using Annexin V-FITC/PI and TUNEL assays; the changes of
      Bax and Bcl2 expressions in the cells were determined using RTPCR and Western
      blotting. RESULTS: Transfection with AQP-5-siRNA resulted in a significant
      reduction (up to 90%) of AQP-5 expression in COLO 205 and SW480 cells. MTT assay
      showed that AQP-5-siRNA transfection significantly inhibited the cell
      proliferation compared NS siRNA transfection (P<0.05). Flow cytometric analysis
      revealed significantly increased apoptotic rate of cells following AQP-5-siRNA
      transfection compared with NS?siRNA transfection(P<0.05). Real-time quantitative
      RT-PCR and Western blotting demonstrated that AQP-5-siRNA transfection
      significantly increased Bax and Bcl-2 expressions at both mRNA and protein levels
      in the cells. CONCLUSION: AQP5-siRNA can promote apoptosis of colorectal cancer
      cells in vitro possibly in relation to its effects on Bax and Bcl expressions.

PMID- 29070463
TI  - [Structural changes of gut microbiota after gastric bypass in obese patients with
      type 2 diabetes].
AB  - OBJECTIVE: To investigate the structural changes inintestinal flora and metabolic
      changes in type 2 diabetic patients with obesity(BMI>=40 kg/m2)by sequencing the
      16S rRNA genes. METHODS: Stool samples were collected from 4 diabetic patients
      before and after gastric bypass surgery for extraction of the total DNA. The
      diversity of the intestinal flora in the samples was investigated by 16S rRNA
      sequencing. After surgery, the changes in glucose and lipid metabolism were
      evaluated in the patients, and the changesin body mass index (BMI) and waist to
      hip ratio were assessed at 3 month intervals. RESULTS: After gastric bypass, the
      patient's BMI, waist to hip ratio, glucose metabolism and lipid metabolism
      gradually recovered the normal levels. The proportion of Bacteroidetesis
      increased and the proportions of Firmicutes and Proteobacteria decreased in the
      intestinal bacteria after the surgery. CONCLUSION: Gastric bypass surgery can
      effectively alleviate the condition of obese patients with type 2 diabetes and
      improve the composition of the intestinal flora.

PMID- 29070465
TI  - [Impact of GOLPH3 expression in cumulus granulosa cells on outcomes of
      intracytoplasmic sperm injection].
AB  - OBJECTIVE: To evaluate the impact of GOLPH3 expression in cumulus granulosa cells
      on the outcomes of intracytoplasmic sperm injection (ICSI). METHODS: A total of
      119 women receiving ICSI due to male infertility at our center between April,
      2012 and June, 2014 were enrolled in the study. Cumulus granulosa cells were
      collected from the women for detection of GOLPH3 expressions using
      immunocytochemistry, Western blotting, and real-time PCR. GOLPH3 expression rate
      was compared between women with and without clinical pregnancy following ICSI,
      and the associations of GOLPH3 expression with the laboratory indicators of ICSI
      outcomes were assessed. RESULTS: Immunocytochemistry showed that GOLPH3
      expression was located mainly in in the plasma of the cumulus granulosa cells.
      The rate and intensity of GOLPH3 expression in the cumulus granulosa cells
      differed significantly between women with and without clinical pregnancy
      following ICSI (P<0.05). GOLPH3 expression was found to positively correlate with
      the numbers of punctured follicles, grade III oocyte cumulus complex, ICSI
      oocytes, fertilized oocytes, cleavage, high quality embryos, blastocysts, high
      quality blastocysts, and frozen embryos (all P<0.01). The results of RTPCR and
      Western blotting revealed significant differences in GOLPH3 expressions at both
      the mRNA and protein levels in the cumulus granulosa cells between the pregnant
      and non-pregnant groups after ICSI (t=14.560, P=0.000). Western blot analysis
      revealed significant difference of GOLPH3 protein expression in cumulus granulosa
      cells between women with and without clinical pregnancy following ICSI.
      CONCLUSION: GOLPH3 expression in the cumulus granulosa cells plays an important
      role in the development of oocytes and promotion of conception to affect the
      outcomes of ICSI.

PMID- 29070464
TI  - [Relationship between cytoplasmic phospholipase A2 and nuclear factor kappaB in
      one lung ventilation-induced lung injury in rabbits].
AB  - OBJECTIVE: To elucidate the mechanisms of up regulated expression of cytoplasmic
      phospholipase A2 (CPLA2) induced by one lung ventilation (OLV) by investigating
      the interactions between nuclear factor kappaB (NF-kappaB) and C-PLA2. METHODS:
      Forty-eight healthy Japanese white rabbits were randomized into control group,
      solvent treatment group (group S), NF-kappaB inhibitor (PDTC)/solvent treatment
      group ( group PS), C-PLA2 inhibitor (AACOCF3)/solvent treatment group (group AS),
      OLV group (group O), solvent treatment plus OLV group (SO group), NFkappaB
      inhibitor (PDTC)/solvent treatment plus OLV group (group PSO) and CPLA2 inhibitor
      (AACOCF3)/solvent treatment plus OLV group (group ASO). ELISA was used to detect
      arachidonic acid (AA) content in the lung tissues, and NFkappaB and CPLA2
      expressions were detected by Western blotting and quantitative PCR. Lung injuries
      were assessed based on the lung histological score, and the polymorphonuclear
      leukocyte count in the bronchial alveolar lavage fluid, myeloperoxidase (MPO)
      content in the lung tissues, and lung wet/dry weight (W/D) raito were determined.
      RESULTS: Treatment of the rabbits with the solvent did not produce any adverse
      effects. OLV caused obvious lung injury in the rabbits and up regulated the
      expressions of CPLA2 and NFkappaB in the lung tissues (P<0.05). In rabbits
      without OLV, treatment with AACOCF3 or PDTC significantly down regulated both
      CPLA2 and NFkappaB expressions without affecting the other parameters. In rabbits
      with OLV, treatment with AACOCF3 or PDTC obviously lowered CPLA2 and NFkappaB
      expressions and lessened the OLV-induced lung injuries. CONCLUSION: Both C-PLA2
      and NF-kappaB play important roles and show interactions in OLV-induced lung
      injury in rabbits.

PMID- 29070466
TI  - [RhoA/Rho-kinase contributes to chronic pain following thoracotomy by up
      regulating glutaminase 1 expression in rat spinal dorsal cord].
AB  - OBJECTIVE: To investigate whether RhoA/Rho-kinase contributes to the occurrence
      of chronic post-thoracotomy pain (CPSP) by up regulation of glutaminase 1 (GLS1)
      expression in the spinal dorsal cord. METHODS: Twenty five male Sprague Dawley
      (SD) rats were divided into control group (n=5) and model group (n=20). The rats
      in the model group were randomized into two sub groups (n=10) for observation on
      day 10 and day 21 after thoracotomy, and each group was further divided into CPSP
      and non CPSP groups according to the behavioral test results. All the rats were
      sacrificed after behavioral test for examination of GLS1 and RhoA expressions in
      the spinal cord using Western blotting and RT PCR. We also compared the effect of
      the Rho kinase inhibitor fasudil and saline, both injected intraperitoneally
      daily at 10 mg/kg for 7 consecutive days following thoracotomy, on CPSP and GLS1
      expression in 30 male SD rats on day 21 after thoracotomy. RESULTS: Compared with
      the control group, the rats with CPSP showed significantly increased expressions
      of GLS1 and RhoA mRNA in the spinal cord on both day 10 and day 21 following
      thoracotomy (P<0.01), but the rats without CPSP did not show obvious changes in
      GLS1 and RhoA expressions. In fasudil treated rats, the mechanical pain threshold
      was obviously increased and the expressions of GLS1 and RhoA were significantly
      reduced as compared with those in saline treated rats (P<0.01). CONCLUSION: RhoA
      plays an important role in the occurence of CPSP by up-regulating the expression
      of GLS1 in the spinal dorsal cord of rats.

PMID- 29070467
TI  - [Comparison of postoperative drainage and systemic trauma response after
      endoscopic and traditional near total thyroidectomy].
AB  - OBJECTIVE: To investigate the difference of postoperative drainage and systemic
      trauma response between endoscopic and traditional near total thyroidectomy to
      provide the basis for selecting appropriate operative methods. METHODS: In this
      prospective clinical controlled study, 80 patientsscheduled for near total
      bilateral thyroidectomy for the first time were divided equally into endoscopic
      surgery group (group A) and open surgery group (group B). The total drainage
      volume after operation, postoperative extubation time, and postoperative daily
      drainage volume were recorded after the operation. The contents of triglyceride
      (TG) and total protein (TP) were determined in the postoperative drainage fluid
      onthe first day. The levels of interleukin 6 (IL6), high sensitive C reactive
      protein (HSCRP), alpha 1 acid glycoprotein (AAG), ceruloplasmin (CER) and
      haptoglobin (HPT) in venous blood were tested before the operation and on the
      first day after surgery. RESULTS: Compared with those in group B, the
      postoperative drainage volumein group Aincreased significantly (P=0.000) and the
      postoperative extubation time was significantly prolonged (P=0.000); the mean
      postoperative daily drainage volume was significantly larger ingroup A than in
      group B (P=0.000) and tended to decrease with time in both groups. There was no
      significant difference in the content of triglycerideortotal protein in the
      drainage fluid between the two groups on the first day after operation (P=0.429
      and 0.324, respectively). In both groups, the contents of AAG, ceruloplasmin and
      haptoglobin on the first postoperative day were all similar with those
      measurement before operation (P>0.05), but significant variations occurred in the
      levels of IL6 and HSCRP on the first postoperative day (P=0.000). The serum
      levels of IL?6 or HS?CRP did not differ significantly between the two groups on
      the first day after operation (P=0.054 and 0.066, respectively). CONCLUSION:
      Compared with open surgery, endoscopic near total bilateral thyroidectomyis
      associated with an increased the volume of postoperative drainage and a prolonged
      time of extubationbut not an increased systemic trauma response. Therefore,
      endoscopic surgery can serve as one of the routine options for patients who are
      concerned with neckscars resulting from open surgeries.

PMID- 29070468
TI  - [Screening and verification of plasma biomarkers for stable angina pectoris: a
      differential proteomic analysis].
AB  - OBJECTIVE: To compare and analyze the differentially expressed plasma proteome
      between patients with stable angina pectoris (SAP) and healthy donors to identify
      the biomarkers for early diagnosis of SAP. METHODS: Plasma samples from 60
      patients with SAP and 60 healthy controls were collected. Twenty samples (100 mL
      each) randomly selected from each group were pooled and after removing high
      abundance proteins from the pooled plasma, two-dimensional gel electrophoresis
      (2DE) was performed to isolate the total proteins. The protein spots with more
      than 2 fold changes were selected after 2D analysis using software, and the
      differentially expressed proteins were identified by MALDI TOF/TOF mass
      spectrometer. ELISA was performed to detect hemoglobin subunit delta (HBD) levels
      in 40 randomly selected samples from each group for verification of the results
      of 2DE. RESULTS: A total of 7 differentially expressed proteins were found in
      plasma samples from patients with SAP, including 3 up regulated proteins (serum
      albumin, hemoglobin subunit alpha and hemoglobin subunit delta,) and 4
      down?regulated ones (apolipoprotein L1, apolipoprotein C3, apolipoprotein E and
      complement C4B). ELISA results showed that HBD level was increased in SAP plasma,
      which was consistent with the results of 2DE. CONCLUSION: Patients with SAP have
      different plasma protein profiles from those of healthy controls, and HBD may
      serve as a potential specific biomarker for early diagnosis of SAP.

PMID- 29070469
TI  - [Splenic thickness combined with routine clinical markers predicts esophageal
      varices in patients with liver cirrhosis].
AB  - OBJECTIVE: To explore the noninvasive indicators for predicting the occurrence of
      esophageal varices (EV) in patients with liver cirrhosis. METHODS: A total of 202
      patients with liver cirrhosis caused by hepatitis B or C or alcoholic hepatic
      disease were enrolled in this study. EV and high risk esophageal varices (HREV)
      were confirmed in these patients by gastroscopy. The hematological, serum
      biochemical and ultrasonic parameters of the patients were analyzed, and a model
      for predicting EV was established by stepwise logistic regression analysis.
      RESULTS: The areas under receiver operating characteristics curve (AUROC) of
      splenic thickness (SPT) for detecting EV and HREV were 0.827 and 0.766,
      respectively. The combined index USWA (SPT, US, WBC and albumin [ALB]) showed an
      AUROC of 0.873 for detecting EV, and the index SPA (combining SPT and ALB) showed
      an AUROC of 0.777 for detecting HREV. The direct combination of SPT with USWA or
      with platelet/splenic thickness ratio (PSA) was capable of completely excluding a
      definite diagnosis of EV, while the sequential combination of SPT with USWA or
      with platelet was capable of a diagnosis of EV and clarifying the condition of EV
      in approximately half of the cirrhotic patients in the absence of gastroscopic
      findings. The combination of SPT and SPA allowed for a definite diagnosis of the
      condition of HREV in 10% of the cirrhotic patients. CONCLUSION: SPT combined with
      SPT derived indexes or platelet status allows for a definite diagnosis of EV in
      patients with liver cirrhosis to offer a noninvasive option for diagnosis.

PMID- 29070470
TI  - [Association between hypertriglyceridemic waist?to?height ratio phenotype and
      chronic kidney disease in a community population in South China: a cross
      sectional study].
AB  - OBJECTIVE: To investigate the relationship between hypertriglyceridemic waist to
      height ratio phenotype (HWHtR) and chronic kidney disease (CKD) in a community
      population in South China. METHODS: A cross sectional study was conducted among
      2142 residents in Zhuhai (Guangdong Province, China) from June to October of
      2012. The HWHtR phenotype was defined as a waist to height ratio(WHtR) >=0.55 and
      triglyceride level >=2.0 mmol/L, based on which the participants were divided
      into HWHtR group and nonHWHtR group. CKD was defined as an eGFR<60 mL/min per
      1.73 m2 or an ACR >=30 mg/g. A logistic regression model was established to
      investigate the relationship between chronic kidney disease and HWHtR phenotype.
      RESULTS: Compared with the nonHWHtR group, the HWHtR group had a higher
      prevalence of chronic kidney disease (11.1% vs 33%, P<0.001). Analysis using the
      logistic regression model showed that HWHtR was significantly associated with CKD
      in the unadjusted analyses (OR=3.23, 95% CI: 2.32-4.48, P<0.001). After
      adjustment for age, sex, history of hypertension, history of diabetes, systolic
      blood pressure, diastolic blood pressure, drinking, physical exercise, education
      and current smoking, HWHtR was significantly associated with CKD (OR=2.36, 95%
      CI: 1.52-3.67, P<0.001); the association of HWHtR and CKD was still significant
      after further adjustment for BMI (OR=2.12, 95%CI: 1.34-3.35, P<0.001).
      CONCLUSION: Our finding suggests that HWHtR is associated with CKD in this
      community population.

PMID- 29070471
TI  - [Snitrosylating protein disulphide isomerase mediates increased expression of
      alpha synuclein caused by methamphetamine in mouse brain].
AB  - OBJECTIVE: To investigate the role of Snitrosylation of protein disulphide
      isomerasec in methamphetamine (METH)-induced expression of alpha synuclein
      (alphaSN) in mouse hippocampus and striatum neurons. METHODS: Forty C57BL/6 mice
      were randomized equally into saline control group, METH group, L-NNA (a NOS
      inhibitor) group and L-NNA plus METH group. All the agents were injected
      intraperitoneally at an interval of 12 h, and a total of 8 injections were
      administered; in L-NNA plus METH group, METH was injected 30 min after LNNA in
      each treatment. Western Blotting was used to detect the expression of nitric
      oxide synthase (NOS), alphaSN, PDI and Snitrosylation of protein disulphide
      isomerase (PDI-SNO) in the hippocampus and striatum of the mice, and nitric oxide
      (NO) levels were determined using a NO assay kit. RESULTS: In METH group, the
      levels of NOS, PDISNO, alphaSN and NO all increased significantly compared with
      those in the control group (P<0.05). Combined treatment with L-NNA and METH,
      compared with METH alone, resulted in significantly lowered expression of NOS,
      NO, PDI-SNO and alphaSN in the hippocampus and striatum of the mice (all P<0.05).
      No significant differences were found in NOS, NO, PDI-SNO or alphaSN expressions
      among METH+L-NNA, L-NNA and control groups (P>0.05). CONCLUSION: METH induces the
      activation of NOS and increases NO level to cause the occurrence of PDI-SNO,
      leading subsequently to increased expression of alphaSN in mouse striatum and
      hippocampus. L-NNA, the inhibitor of NOS, can partly relieve nervous system
      toxicity induced by METH.

PMID- 29070473
TI  - [Surgical correction of conjunctival sac narrowing after orbital implantation
      using polyester fiber heart patches].
AB  - OBJECTIVE: To test the feasibility of correcting conjunctival sac narrowing
      following orbital implantation using polyester fiber heart patches instead of the
      skin autograft. METHODS: Twelve patients of conjunctival sac narrowing after
      orbital implantation (including 3 with orbital implant exposure) admitted in
      Nanfang Hospital between 2012 and 2016 received surgical correction of the
      conjunctival sac using polyester fiber heart patches. During the surgery, the
      central conjunctival sac was opened, the exposed area was covered with suitable
      polyester fiber heart patches, and the palpebral margin was sutured. RESULTS:
      Three months after the operation, 10 patients showed improved appearance after
      implantation of the prosthetic eye. Two patients received a second operation to
      remove the patches due to graft rejection and infections and skin autograft was
      implanted for reconstruction of the conjunctival sac. CONCLUSION: Polyester fiber
      heart patches are ideal materials for repairing Conjunctival sac narrowing and
      orbital implant exposure, but this approach is not suitable in cases of severe
      narrowing or occlusion of the conjunctival sac.

PMID- 29070472
TI  - [Breakthrough bleeding in adult patients with severe hemophilia A receiving low-
      and intermediate-dose FVIII for tertiary prophylaxis: characteristics and
      influencing factors].
AB  - OBJECTIVE: To investigate the characteristics of breakthrough bleeding in adult
      patients with severe hemophilia A (SHA) receiving low- and intermediate-dose
      FVIII for tertiary prophylaxis and explore the factors affecting the outcomes of
      the treatment. METHODS: Forty-nine patients (mean age 31.53?7.33 years) with SHA
      receiving tertiary prophylaxis FVIII treatment were divided into low-dose group
      (n=15) and intermediate-dose group (n=34). The data including clinical bleeding
      phenotype (Pre?AJBR), 72 h FVIII trough activity, and Functional Independence
      Score in Hemophilia (FISH) were recorded in all the patients, and Hemophilia
      Steward APP was used to record the bleeding episode and the treatment data. All
      the patients were followed up for at least 6 months. RESULTS: In the low-dose and
      intermediate-dose groups, the number of joint bleeding (AJBR) episodes were
      18.79?13.03 and 9.28?7.02 per year (P=0.016), and the proportions of spontaneous
      bleeding were 75.0% and 47.7%, respectively. The proportions of patients with
      target joint were 80% and 44%, target joint bleeding occurred in 59% and 41%, and
      cataract bleeding after 0-12 h of prophylactic injection occurred in 4.86% and
      5.18% of the patients with a median breakthrough bleeding time of 40.08 h and
      46.08 h (P=0.008), respectively. The proportions of patients with 72 h FVIII
      trough activity <1% were 44.4% and 34.8% in the two groups, respectively. AJBR
      was negatively correlated with the preventive dose consumed (r=-0.57, P=0.000,
      n=49) and FISH, but positively correlated with Pre-AJBR in the two groups
      (P<0.05). CONCLUSION: Tertiary prophylaxis with low- and intermediate-dose FVIII
      is not sufficient to achieve the goal of preventing progression of joint disease
      in Chinese adult patients with SHA. Although the prophylactic dose is the most
      important factor to affect the treatment efficacy, other non-factor approaches
      may also help to improve the efficacy of the treatment.

PMID- 29070474
TI  - [Histological structure of the trabecular meshwork in the eyeball: challenging
      the traditional concept and preliminary findings in rabbits, rats and mice].
AB  - OBJECTIVE: To verify that the trabecular meshwork (TM) in the wall of the eyeball
      consists of smooth muscle fibers instead of collagen fibers or endothelial cells.
      METHODS: Eighteen fresh eyeballs from 3 rabbits, 3 SD rats and 3 mice were
      sectioned along the sagittal plane and sliced after paraffin embedding for HE
      staining, VG staining, Masson staining, alpha-SMA immunohistochemistry or CD31
      immunohistochemistry. These slices were observed under microscope and the
      structure of the TM was compared with those of scleral collagen fibers, ciliary
      muscles and endothelial cells. RESULTS: HE staining of the eyeball slices from
      the 3 animal species resulted in purplish red staining of the TM, which was
      highly consistent with ciliary muscle fibers. The cell?like structures on the
      surface of the TM were not clearly outlined, with flat nuclei showing a dark
      purple staining; these structures did not show obvious boundaries from the TM.
      Ciliary muscle fibers, which were smooth muscle cells in nature, were aligned in
      bundles in various directions. The longitudinally sectioned cells were flat and
      contained purplish cytoplasm and highly flattened nuclei. Scleral collagen fibers
      were stained dark red with a few fibroblasts sandwiched among them. The long axis
      of the fibroblasts was in parallel with that of the collagen fibers. The outline
      of the fibroblast was not clear and the nucleus was flat in dark blue. The
      vascular endothelial cells presented with different morphologies and contained
      light purplish cytoplasm and dark nuclei, protruding into the vascular cavity. VG
      staining of the TM revealed a pale red filamentous structure, and the collagen
      fibers were stained bright red. Masson staining of the TM showed a reticular
      structure consisting mainly of dark red fibers intermingled with thin green
      fibers. Scleral collagen fibers presented with a cord?like green wavy structure.
      The endothelial cells were green and flat, while the ciliary smooth muscle fibers
      were purple. In immunohistochemistry for alpha?SMA, the TM and the ciliary smooth
      muscle fibers showed a strong positivity in the cytoplasm, while the scleral
      collagen fibers and vascular endothelial cells showed negative staining;
      immunohistochemistry for CD31 showed no obvious positive staining in the TM,
      collagen fibers or ciliary smooth muscle cells from all the animals in spite of
      slight differences among them. CONCLUSION: The TM consists mainly of smooth
      muscle fibers with a thin layer of peripheral endomysium without endothelial
      cells.

PMID- 29070475
TI  - [Effect of resveratrol on forelimb grip strength and myofibril structure in aged
      rats].
AB  - OBJECTIVE: To observe the effect of resveratrol on muscle mass, forelimb grip
      strength, myofibril structure and AMPK/sirt1 pathway in skeletal muscles of aged
      rats. METHODS: Twenty aged (25 months old) SD rats were randomly divided into
      aged control group and resveratrol treatment group (10 in each group) with 10
      young (6 months old) rats served as the young control group. In resveratrol
      treatment group, the rats were treated with resveratrol (mixed in chow) for 6
      weeks. After the treatment, the mass of the gastrocnemius was measured and the
      sarcopenia index (SI) was calculated as the gastrocnemius mass (mg) to body
      weight (g) ratio. The forelimb grip strength of the rats was measured using a
      electronic grip strength meter, and the lengths of the sarcomere, I-band, A-band
      and H-zone of the myofibrils were determined by transmission electron microscopy.
      RESULTS: Compared with the young rats, the aged control rats had significantly
      lower SI of the gastrocnemius (P<0.05) and grip strength (P<0.05) with increased
      lengths of the sarcomere, A-band, I-band and H-zone (P<0.05) and lowered
      expressions of AMPK, P-AMPK, and sirt1 protein (P<0.05). Resveratrol treatment of
      the aged rats significantly increased the forelimb grip strength, reduced the
      lengths of sarcomere length, I-band and H-zone (P<0.05) and increased, P-AMPK,
      sirt1 protein expressions (P<0.05) without significantly affecting the SI
      (P>0.05) or the A-band length (P>0.05). CONCLUSION: Resveratrol does not improve
      the muscle mass but can increase the forelimb grip strength in aged rats possibly
      by activating AMPK/sirt1 pathway to improve the ultrastructure of the myofibrils.

PMID- 29070476
TI  - [Correlations between apparent diffusion coefficient in diffusion?weighted
      magnetic resonance imaging and molecular subtypes of invasive breast cancer
      masses].
AB  - OBJECTIVE: To study the correlation of apparent diffusion coefficient (ADC)
      measured by diffusion-weighted magnetic resonance imaging (MRI) with the
      molecular subtypes and biological prognostic factors of invasive breast cancer
      masses. METHODS: Breast MRI data (including dynamic enhanced and diffusion
      weighted imaging) were collected from 64 patients with pathologically confirmed
      invasive breast cancer masses (a total of 69 lesions). The mean ADC values of the
      lesions were calculated and their correlations were analyzed with the 5 molecular
      subtypes of invasive breast cancer and the biological prognostic factors
      including estrogen receptor (ER), progesterone receptor (PR), human epidermal
      growth factor 2 (HER2), and Ki-67 index. RESULTS: The ADC values did not differ
      significantly among the 5 molecular subtypes of invasive breast cancer masses
      (P>0.05) or among lesions with different ER, PR, or HER2 status (P>0.05). The
      mean ADC values were significantly higher in Ki-67-positive lesions than in the
      negative lesions (P=0.023 and negatively correlated with the expressions of Ki-67
      (r=-0.249). CONCLUSION: ADC value can not be used to identify the molecular
      subtypes of invasive breast cancer masses or to evaluate the biological prognosis
      of the lesions, but its correlation with Ki-67 expression may help in prognostic
      evaluation and guiding clinical therapy of the tumors.

PMID- 29070477
TI  - [Endoscopic analysis of early esophageal cancer and precancerous lesions in
      Kazakh patients].
AB  - OBJECTIVE: To explore the value of endoscopic narrow-band imaging in the
      diagnosis of early-stage esophageal cancer and precancerous lesions in Kazakh
      patients. METHODS: A total of 106 Kazakh patients with esophageal mucosa lesions
      diagnosed by routine endoscopy in our hospital from January 2014 to July 2016
      were enrolled in this analysis with 30 randomly selected patients with normal
      endoscopic findings of the esophageal mucosa as the control group. The
      morphological changes of papillary capillary loop (IPCL) of the esophageal
      epithelium in the two groups were observed by narrow-band imaging magnifying
      endoscopy. Pathological examinations were performed for all the patients with
      esophageal mucosa lesions. RESULTS: In patients with esophageal mucosa lesions,
      10 were diagnosed to have early esophageal cancer, 16 had low-grade tumors, 11
      had high-grade tumors and 69 had esophagitis. IPCL typing results showed IPCL
      type I in all the control subjects, predominantly type IV in patients with early
      esophageal carcinoma, type II and III in patients with low-grade tumor, type III
      in patients with high-grade tumor, and type II in patients with esophagitis.
      CONCLUSION: The location and size of the esophageal lesions can be observed
      clearly by narrow-band imaging magnifying endoscopy. The histopathology of the
      esophageal mucosa can be analyzed with IPCL classification for diagnosis of early
      esophageal cancer and precancerous lesions in Kazakhs.

PMID- 29070478
TI  - [Successful pregnancy following intracytoplasmic sperm injection?embryo transfer
      in a patient with premature ovarian insufficiency: a case report].
AB  - OBJECTIVE: We report a case of ovarian function fluctuation during long-term
      follow-up in a patient with premature ovarian insufficiency (POI). The patient
      finally obtained clinical pregnancy with subsequent uneventful full-term delivery
      after several intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles.
      This case demonstrates that hormone replacement therapy (HRT) and assisted
      reproductive therapy should be applied as soon as possible to young patients with
      POI who have a strong desire for pregnancy in the absence of contraindications.
      This strategy helps such patients obtain pregnancy and delivery before the
      exhaustion of ovarian function.

PMID- 29070479
TI  - [Current progress in research of circulating tumor cells].
AB  - OBJECTIVE: Circulating tumor cells are tumor cells that spontaneously or,
      following operations, migrate into the peripheral blood circulation from the
      primary tumor or metastatic tumor. As diagnostic, prognostic and predictive
      biomarkers in many types of cancers including breast cancer, lung cancer,
      pancreatic cancer and colorectal cancer, circulating tumor cells contribute to
      the early diagnosis of cancers, drug resistance monitoring, prognostic
      assessment, survival analysis, detection of tumor recurrence and evaluation of
      drug efficacy to assist in treatment decision?making and adjustment of treatment
      plans. However, the current approaches to the detection of circulating tumor
      cells still have limitations, and the development of new detection methods with
      higher sensitivity and specificity will be helpful for better use of these cells.
      Herein the authors review the research progress in circulating tumor cells in
      terms of the detection techniques, clinical applications of circulating tumor
      cells, and their prospects in future clinical practice.

PMID- 29070482
TI  - Design and synthesis of yeast chromosomes.
AB  - With the rapid growth and development of synthetic biology, research in the
      genomics is advancing from genome sequencing to genome synthesis. In 2009,
      Professor Jef D. Boeke proposed the Synthetic Yeast Genome Project (Sc2.0), which
      aims to synthesize the world's first eukaryotic genome. With the efforts of
      scientists from the United States, China, Britain, France, Australia, Singapore
      and other countries, a third of the Saccharomyces cerevisiae chromosomes has now
      been synthesized. In the perspectives of synthetic genomics, we here review the
      recent progress in the Sc2.0 project, including discussion on the right arm of
      chromosome 9, and chromosomes 2, 5, 6, 10, 12, in terms of their designs and
      synthetic strategy as well as the biological significance, thereby providing a
      reference for further research in synthetic genomics.

PMID- 29070481
TI  - Examining Internet and eHealth Practices and Preferences: Survey Study of
      Australian Older Adults With Subjective Memory Complaints, Mild Cognitive
      Impairment, or Dementia.
AB  - BACKGROUND: Interest in electronic health (eHealth) technologies to screen for
      and treat a variety of medical and mental health problems is growing
      exponentially. However, no studies to date have investigated the feasibility of
      using such e-tools for older adults with mild cognitive impairment (MCI) or
      dementia. OBJECTIVE: The objective of this study was to describe patterns of
      Internet use, as well as interest in and preferences for eHealth technologies
      among older adults with varying degrees of cognitive impairment. METHODS: A total
      of 221 participants (mean age=67.6 years) attending the Healthy Brain Ageing
      Clinic at the University of Sydney, a specialist mood and memory clinic for
      adults >=50 years of age, underwent comprehensive clinical and neuropsychological
      assessment and completed a 20-item self-report survey investigating current
      technology use and interest in eHealth technologies. Descriptive statistics and
      Fisher exact tests were used to characterize the findings, including variability
      in the results based on demographic and diagnostic factors, with diagnoses
      including subjective cognitive impairment (SCI), MCI, and dementia. RESULTS: The
      sample comprised 27.6% (61/221) SCI, 62.0% (137/221) MCI, and 10.4% (23/221)
      dementia (mean Mini-Mental State Examination=28.2). The majority of participants
      reported using mobile phones (201/220, 91.4%) and computers (167/194, 86.1%)
      routinely, with most respondents having access to the Internet at home (204/220,
      92.6%). Variability was evident in the use of computers, mobile phones, and
      health-related websites in relation to sociodemographic factors, with younger,
      employed respondents with higher levels of education being more likely to utilize
      these technologies. Whereas most respondents used email (196/217, 90.3%), the use
      of social media websites was relatively uncommon. The eHealth intervention of
      most interest to the broader sample was memory strategy training, with 82.7%
      (172/208) of participants reporting they would utilize this form of intervention.
      Preferences for other eHealth interventions varied in relation to educational
      level, with university-educated participants expressing greater interest in
      interventions related to mood (P=.01), socialization (P=.02), memory (P=.01), and
      computer-based exercises (P=.046). eHealth preferences also varied in
      association, with diagnosis for interventions targeting sleep (P=.01), nutrition
      (P=.004), vascular risk factors (P=.03), and memory (P=.02). CONCLUSIONS:
      Technology use is pervasive among older adults with cognitive impairment, though
      variability was noted in relation to age, education, vocational status, and
      diagnosis. There is also significant interest in Web-based interventions
      targeting cognition and memory, as well as other risk factors for cognitive
      decline, highlighting the urgent need for the development, implementation, and
      study of eHealth technologies tailored specifically to older adults, including
      those with MCI and early dementia. Strategies to promote eHealth use among older
      adults who are retired or have lower levels of education will also need to be
      considered.

PMID- 29070480
TI  - Internet-Delivered Dialectical Behavioral Therapy Skills Training for Suicidal
      and Heavy Episodic Drinkers: Protocol and Preliminary Results of a Randomized
      Controlled Trial.
AB  - BACKGROUND: The need to develop effective and accessible interventions for
      suicidal individuals engaging in heavy episodic drinking (HED) cannot be
      understated. While the link between alcohol use and suicidality is a complex one
      that remains to be elucidated, emotion dysregulation may play a key role in
      alcohol-related suicide risk in these individuals. OBJECTIVE: In the current
      study, an 8-week Internet-delivered dialectical behavior therapy (DBT) skills
      training intervention was developed and preliminarily evaluated for suicidal
      individuals who engage in HED to regulate emotions. The aim of the study is to
      evaluate the feasibility and effectiveness of the therapist-assisted and Internet
      delivered intervention, and to inform the design of a subsequent full-scale
      study. METHODS: The study was a pilot randomized controlled trial comparing
      participants receiving immediate-treatment (n=30) to waitlist controls (n=29)
      over a period of 16 weeks. Intervention effects will be assessed longitudinally
      using hierarchical linear modeling and generalized estimating equations, along
      with analyses of effect sizes and clinically significant change. The primary
      outcomes are suicidal ideation, alcohol problems, and emotion dysregulation.
      Secondary outcomes include alcohol-related consequences, reasons for living,
      skills use, and depression. RESULTS: The trial is ongoing. A total of 60
      individuals returned their informed consent and were randomized, of whom 59
      individuals were intended to treat. A total of 50 participants in the study were
      retained through the 16-week enrollment. CONCLUSIONS: There is a dearth of
      evidence-based treatment for individuals presenting with high risk and complex
      behaviors. Furthermore, computerized interventions may provide a beneficial
      alternative to traditional therapies. The particular clinical features and
      treatment needs of suicidal individuals who also engage in HED constitute key
      domains for further investigation that are needed to consolidate the design of
      appropriate interventions for this high-risk population. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02932241; https://clinicaltrials.gov/ct2/show/NCT02932241
      (Archived by WebCite at http://www.webcitation.org/6uJHdQsC2).

PMID- 29070483
TI  - Research progress of myosin heavy chain genes in human genetic diseases.
AB  - Myosins constitute a large superfamily proteins, which convert chemical energy,
      through ATP hydrolysis, to mechanical force for diverse cellular movements, such
      as cell migration and muscle contraction. The class II myosin forms the filaments
      in muscle and non-muscle cells as a hexameric protein complex, consisting of two
      myosin heavy chain (MyHC) subunits and two pairs of non-identical light chain
      subunits. There are several MyHC isoforms encoded by different genes of the MYH
      family in humans. At present, distinct mutations in different genes of the MYH
      family are associated with various human genetic diseases. Mutations in MYH2 are
      associated with skeletal myopathies, characterized by ophthalmoplegia. Mutations
      in MYH3 and MYH8 are associated with distal arthrogryposis syndromes. Mutations
      in MYH7 are associated with not only skeletal muscle diseases, such as Laing
      distal myopathy and myosin storage myopathy, but also hypertrophic
      cardiomyopathy. Mutations in MYH9 are associated with the so-called MYH9-related
      disease, characterized by giant platelets, thrombocytopenia and granulocyte
      inclusions. In this review, we briefly discuss the expression patterns of the MYH
      gene family and summarize the research progress in correlating the abnormalities
      of MYH gene family with various human genetic diseases.

PMID- 29070484
TI  - Epigenetics regulates gene expression patterns of skeletal muscle induced by
      physical exercise.
AB  - As it is well known, proper exercise benefits our mind and body, especially the
      skeletal muscle. Exercise increases the capacity of muscle metabolism, enhances
      the biological function of mitochondria, regulates the transformation of muscle
      fiber types and increases the muscle power. In recent years, more and more
      researches show that epigenetic regulation plays an important role in
      strengthening the muscle, and these studies mainly include DNA methylation,
      histone modification, and regulation of miRNA expression. In order to adapt to
      the body movement, these three epigenetic patterns change the metabolic capacity
      of skeletal muscle, mitochondrial biological function and muscle fiber types by
      regulating the gene expression of skeletal muscle. In this review, we summarize
      research progresses of exercise-induced epigenetic regulation of gene expression
      of skeletal muscle, in order to provide a reference for further studies of how
      sports improve our body health.

PMID- 29070485
TI  - Functions of Wnt signaling pathway in hair cell differentiation and regeneration.
AB  - Wnt signaling pathway plays important roles in the development and homeostasis of
      multicellular organisms. Through their bindings with the Frizzled receptors, the
      Wnt ligands regulate a wide range of developmental processes, such as axis
      patterning, cell division, and cell fate specification. Wnt signaling plays vital
      roles in the development of inner ear of the mouse. In the early stages of inner
      ear development, Wnt signaling specifies the size of the placode and the
      formation of the otic vesicle. In later stages, Wnt signaling mediates hair cell
      specification and orients the stereociliary bundles in a uniform direction. In
      this review, we summarize the current knowledge on the roles of Wnt signaling in
      hair cell differentiation and regeneration, which may provide references and
      insights for investigators in the field.

PMID- 29070486
TI  - The functions of PEX genes in peroxisome biogenesis and pathogenicity in
      phytopathogenic fungi.
AB  - Peroxisomes are cellular organelles present ubiquitously in eukaryotic cells and
      are involved in beta-oxidation, glyoxylate cycle and a variety of biochemical
      metabolisms. Recently peroxisomes have been demonstrated to play vital roles in
      the host infection processes by plant fungal pathogens. The biogenesis of
      peroxisomes requires a category of proteins named peroxins, which are encoded by
      the PEX genes. So far, more than 10 PEX genes were isolated in phytopathogenic
      fungi, and significant research efforts are focused on the mechanism of
      peroxisome formation and the roles of peroxisome in the development and
      pathogenicity of fungal pathogens. In this review, we summarize the latest
      advances in peroxisome biogenesis and functions in pathogenic fungi, including
      the roles of PEXs in life cycle of peroxisome, peroxisome related metabolisms,
      and fungal development, infection and pathogenicity, in order to provide
      references for future studies in plant pathogenic fungi and the control of
      disease.

PMID- 29070487
TI  - A multigene phylogentic analysis of Potato virus Y and its application in strain
      identification.
AB  - The objective of this study is to develop a rapid and accurate multigene
      phylogenetic analysis to identify Potato virus Y (PVY) strains. The phylogenetic
      relationships of strains within the PVY species were evaluated with isolate
      strain association using five datasets of concatenated sequences from the P1, HC
      pro, VPg and CP genes to determine the best dataset for PVY strain
      identification. Results from phylogenetic analyses and Bayesian tip-association
      significance (BaTS) tests indicated that the major PVY strains could be
      distinguished using the P1, VPg and CP concatenated sequences datasets but not
      the remaining concatenated sequence datasets. Phylogenetic trees reconstructed
      from the concatenated sequences of P1, VPg and CP genes revealed that the ML and
      NJ trees had broadly similar topologies and that both were better than the
      maximum clade credibility tree (MCC). Additionally, the full genome of HLJ26, one
      isolate randomly selected for the multigene phylogenetic analysis, was clustered
      with high confidence among members of the PVYNTN-NW (SYR-II) strain, which
      includes isolates of SYR-II-2-8, SYR-II-Be1 and SYR-II-DrH. This suggests that it
      was a PVYNTN-NW (SYR-II) isolate. Recombination analysis of this isolate
      identified four putative recombination joints in the P1, HC-pro/P3, VPg and the
      5'-terminus of CP. This pattern is similar to that observed in the genomic
      structure of PVYNTN-NW (SYR-I), supporting the classification of this isolate as
      the PVYNTN-NW strain (SYR-II). Simultaneously, two expected fragments of
      approximately 1 000 and 400 bp in size were also amplified from the isolate by a
      multiplex RT-PCR, consistent with the expected band pattern of the PVYNTN-NW (SYR
      II) strain. This further supports the utility of the multigene phylogenetic
      method in identifying PVY strains. We propose that the major PVY strains could be
      distinguished accurately using multigene phylogenetic analysis based on the
      concatenated sequences from the P1, VPg and CP genes.

PMID- 29070488
TI  - Effects of parameters, plasmid dosages and topological structures on transfection
      efficiency of porcine fetal fibroblasts using different electroporators.
AB  - To obtain an ideal transfection efficiency of porcine fetal fibroblasts,
      fluorescence activated cell sorting (FACS) was used to optimize parameters for
      transfection of porcine fetal fibroblasts (PFFs) with ECM? 830, NEPA 21 and
      Nucleofector? 2b in different conditions such as electroporation parameters,
      plasmid dosages and topological structures. The results show that the optimum
      poring pulse parameter of NEPA 21 is voltage 200 V, continuous 3 ms, interval 50
      ms, 3 times, voltage attenuation range of 10%; and the transfection efficiency of
      Nucleofector? 2b is highest under U-023 program. Under the optimum conditions,
      FACS analysis demonstrates that Nucleofector? 2b and ECM? 830 have the highest
      transfection efficiency when transfecting 10 MUg supercoiled plasmids into PFFs,
      and 8 MUg for NEPA 21. Supercoiled plasmids show higher transfection efficiencies
      than linearized plasmids. Moreover, Nucleofector? 2b has the highest transfection
      efficiency among the three electroporation instruments. This study paves the way
      to generate transgenic or gene editing pigs with high efficiency.

PMID- 29070489
TI  - Application of case teaching in genetics courses to students majoring in
      forestry.
AB  - Undergraduate students majoring in forestry generally reflect that genetics is
      one of the most difficult compul-sory courses, because the traditional teaching
      method is difficult to satisfy their needs. According to the theoretical charac
      teristics of forestry and actual demands of the students, in the light of
      teaching and research experience in recent years, we adopted a series of typical
      genetic cases such as 'opening coffin to identify relatives', stem-throne of
      Lycium ruthenicum Murr, and magic powers in Harry Potter. Our practices revealed
      that the case teaching in genetics could train good personality traits, learning
      abilities and creativity of the students, stimulate their interests and
      initiatives in learning, and increase systematic learning.

PMID- 29070490
TI  - The diverse cellular responses of the choroid plexus during infection of the
      central nervous system.
AB  - The choroid plexus (CP) is responsible for the production of a large amount of
      the cerebrospinal fluid (CSF). As a highly vascularized structure, the CP also
      presents a significant frontier between the blood and the central nervous system
      (CNS). To seal this border, the epithelium of the CP forms the blood-CSF barrier,
      one of the most important barriers separating the CNS from the blood. During the
      course of infectious disease, cells of the CP can experience interactions with
      intruding pathogens, especially when the CP is used as gateway for entry into the
      CNS. In return, the CP answers to these encounters with diverse measures. Here,
      we will review the distinct responses of the CP during infection of the CNS,
      which include engaging of signal transduction pathways, the regulation of gene
      expression in the host cells, inflammatory cell response, alterations of the
      barrier, and, under certain circumstances, cell death. Many of these actions may
      contribute to stage an immunological response against the pathogen and
      subsequently help in the clearance of the infection.

PMID- 29070492
TI  - Vitamin D deficiency: infertility and neurodevelopmental diseases (attention
      deficit hyperactivity disorder, autism, and schizophrenia).
AB  - The process of development depends on a number of signaling systems that
      regulates the progressive sequence of developmental events. Infertility and
      neurodevelopmental diseases, such as attention deficit hyperactivity disorder,
      autism spectrum disorders, and schizophrenia, are caused by specific alterations
      in these signaling processes. Calcium signaling plays a prominent role throughout
      development beginning at fertilization and continuing through early development,
      implantation, and organ differentiation such as heart and brain development.
      Vitamin D plays a major role in regulating these signaling processes that control
      development. There is an increase in infertility and an onset of
      neurodevelopmental diseases when vitamin D is deficient. The way in which vitamin
      D deficiency acts to alter development is a major feature of this review. One of
      the primary functions of vitamin D is to maintain the phenotypic stability of
      both the Ca2+ and redox signaling pathways that play such a key role throughout
      development.

PMID- 29070494
TI  - Small hospitals can offer big residency experiences.

PMID- 29070495
TI  - Hurricane Irma spares Putnam Community Medical Center.

PMID- 29070491
TI  - RhoA increases ASIC1a plasma membrane localization and calcium influx in
      pulmonary arterial smooth muscle cells following chronic hypoxia.
AB  - Increases in pulmonary arterial smooth muscle cell (PASMC) intracellular Ca2+
      levels and enhanced RhoA/Rho kinase-dependent Ca2+ sensitization are key
      determinants of PASMC contraction, migration, and proliferation accompanying the
      development of hypoxic pulmonary hypertension. We previously showed that acid
      sensing ion channel 1a (ASIC1a)-mediated Ca2+ entry in PASMC is an important
      constituent of the active vasoconstriction, vascular remodeling, and right
      ventricular hypertrophy associated with hypoxic pulmonary hypertension. However,
      the enhanced ASIC1a-mediated store-operated Ca2+ entry in PASMC from pulmonary
      hypertensive animals is not dependent on an increase in ASIC1a protein
      expression, suggesting that chronic hypoxia (CH) stimulates ASIC1a function
      through other regulatory mechanism(s). RhoA is involved in ion channel
      trafficking, and levels of activated RhoA are increased following CH. Therefore,
      we hypothesize that activation of RhoA following CH increases ASIC1a-mediated
      Ca2+ entry by promoting ASIC1a plasma membrane localization. Consistent with our
      hypothesis, we found greater plasma membrane localization of ASIC1a following CH.
      Inhibition of RhoA decreased ASIC1a plasma membrane expression and largely
      diminished ASIC1a-mediated Ca2+ influx, whereas activation of RhoA had the
      opposite effect. A proximity ligation assay revealed that ASIC1a and RhoA
      colocalize in PASMC and that the activation state of RhoA modulates this
      interaction. Together, our findings show a novel interaction between RhoA and
      ASIC1a, such that activation of RhoA in PASMC, both pharmacologically and via CH,
      promotes ASIC1a plasma membrane localization and Ca2+ entry. In addition to
      enhanced RhoA-mediated Ca2+ sensitization following CH, RhoA can also activate a
      Ca2+ signal by facilitating ASIC1a plasma membrane localization and Ca2+ influx
      in pulmonary hypertension.

PMID- 29070496
TI  - Administration of crushed ledipasvir-sofosbuvir tablets via gastrostomy button in
      a patient coinfected with HIV and hepatitis C virus.

PMID- 29070497
TI  - Inpatient pharmacy experience with an audit for a risk evaluation and mitigation
      strategy for riociguat.

PMID- 29070498
TI  - Impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus
      surveillance protocol.
AB  - PURPOSE: Results of a study to evaluate the impact of a pharmacist-driven
      methicillin-resistant Staphylococcus aureus (MRSA) surveillance screening
      protocol are reported. METHODS: A retrospective single-center, quasi
      experimental, pre-post cohort study was conducted to assess medication-use and
      clinical outcomes before and after implementation of a protocol allowing
      pharmacists to order nasal swabs and polymerase chain reaction (PCR) testing for
      MRSA in selected patients receiving vancomycin for pneumonia or acute
      exacerbation of chronic obstructive pulmonary disease (AECOPD). Negative assay
      results were used to guide de-escalation of vancomycin therapy. The primary
      outcome was vancomycin days of therapy (DOT). Secondary outcomes included
      hospital length of stay, the rate of vancomycin-associated acute kidney injury,
      and in-hospital mortality. RESULTS: A total of 300 patients were identified for
      inclusion in the preprotocol group (n = 150) or postprotocol group (n = 150)
      through medical records review. Compared with patients in the preprotocol group,
      those in the postprotocol group had a median 2.1-day reduction in vancomycin DOT
      (2.1 days versus 4.2 days, p < 0.0001). Protocol implementation was also
      associated with a decrease in the median number of vancomycin serum levels
      obtained per patient but did not have a significant impact on other secondary
      outcomes. CONCLUSION: Among patients with suspected or confirmed pneumonia or an
      AECOPD, the expansion of pharmacists' traditional scope of practice to include a
      surveillance protocol using a MRSA PCR nares assay to guide vancomycin de
      escalation resulted in a reduction in vancomycin utilization without compromising
      clinical outcomes.

PMID- 29070499
TI  - Identifying and characterizing preventable adverse drug events for prioritizing
      pharmacist intervention in hospitals.
AB  - PURPOSE: The approach and results for identifying and characterizing preventable
      adverse drug events (pADEs) that are key targets for pharmacist medication
      therapy management (MTM) are summarized. METHODS: This study was part of a larger
      effort aimed at developing an electronic health record-based prediction model
      (the complexity score, or C-score) that ranks hospitalized patients according to
      their risk for pADEs. An environmental scan of published epidemiologic pADE
      studies and national patient safety priority areas was conducted. The final list
      of candidate pADEs was then disseminated to ASHP members and a national technical
      expert panel (TEP) to evaluate the importance, prevalence, severity,
      preventability, and measurability of these pADEs. Polychoric correlation tests
      were performed to evaluate and quantify associations between importance and any
      of the constructs' mean rankings for each individual pADE. RESULTS: The
      environmental scan yielded a total of 21 candidate pADEs, including drug-induced
      acute kidney injury, falls, respiratory depression, altered mental status,
      hemorrhage, hepatic failure, hypoglycemia, seizures, hypotension and bradycardia,
      ileus, blood dyscrasias, severe electrolyte imbalances, prolonged hyperglycemia,
      uncontrolled hypertension, uncontrolled arrhythmia, stress ulcers, hospital
      acquired infections, uncontrolled hospital-acquired or community-acquired
      infection, uncontrolled pain, and venous thromboembolism. The survey confirmed
      all pADEs were important. Ranking of overall importance was mainly driven by
      perceived pADE severity and, to a lesser extent, by preventability and prevalence
      ratings. CONCLUSION: A literature review and survey of ASHP and TEP members were
      used to compile a list of important hospital-acquired pADEs for incorporation
      into a model for prioritizing patients for MTM services.

PMID- 29070500
TI  - Survey of collaborative drug therapy management in U.S. hospitals.
AB  - PURPOSE: Results of a survey assessing the extent and scope of collaborative drug
      therapy management (CDTM) in U.S. hospitals are presented. METHODS: A survey
      questionnaire was mailed to a national random sample of hospital pharmacies.
      Pharmacy directors provided data on CDTM activities; their views on support for
      CDTM, the financial and strategic impact of CDTM, and the effect of state
      regulations on CDTM practice were assessed using summative Likert-type scales.
      Logistic regression was performed to assess associations of respondent
      demographics and hospital characteristics with CDTM use. RESULTS: The usable
      response rate was 30.2%. Pharmacists were reported to be engaged in CDTM in 66%
      of respondents' hospitals, a significantly (p < 0.0001) greater proportion than
      reported in a comparable 2003 survey. The most prevalent CDTM activities were
      ordering laboratory and related tests (58.7% of hospitals), adjusting drug
      strength (57.9%), and changing the frequency of administration (53.8%). The most
      commonly reported diseases or treatment areas for CDTM use were anticoagulation
      (52.4% of hospitals), infectious diseases (44.8%), and parenteral nutrition
      (32.6%). CONCLUSION: From 2003 to 2013, the prevalence of CDTM use in surveyed
      U.S. hospitals increased significantly, from about 50% to 66%. The 3 most common
      specific CDTM activities in 2003-ordering test results, adjusting drug strength,
      and changing frequency of administration-were still the most common in 2013 but
      were allowed at higher percentages of hospitals.

PMID- 29070501
TI  - Centers for Medicare and Medicaid Services' Decision to Reconsider Coverage
      Indications for ICDs: Where to Now?

PMID- 29070502
TI  - Prognostic Value of Follow-Up Hemodynamic Variables After Initial Management in
      Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Hemodynamic variables such as cardiac index and right atrial pressure
      have consistently been associated with survival in pulmonary arterial
      hypertension (PAH) at the time of diagnosis. Recent studies have suggested that
      pulmonary arterial compliance may also predict prognosis in PAH. The prognostic
      importance of hemodynamic values achieved after treatment initiation is less well
      established. METHODS: Our objective was to evaluate the prognostic importance of
      clinical and hemodynamic variables during follow-up, including pulmonary arterial
      compliance, after initial management in PAH. We evaluated incident patients with
      idiopathic, drug- and toxin-induced, or heritable PAH enrolled in the French
      pulmonary hypertension registry between 2006 and 2016 who had a follow-up right
      sided heart catheterization (RHC). The primary outcome was death or lung
      transplantation. We used stepwise Cox regression and the Kaplan-Meier method to
      assess variables obtained at baseline and at first follow-up RHC. RESULTS: Of 981
      patients, a primary outcome occurred in 331 patients (33.7%) over a median follow
      up duration of 2.8 years (interquartile range, 1.1-4.6 years). In a multivariable
      model considering only baseline variables, no hemodynamic variables independently
      predicted prognosis. Median time to first follow-up RHC was 4.6 months
      (interquartile range, 3.7-7.8 months). At first follow-up RHC (n=763), New York
      Heart Association functional class, 6-minute walk distance, stroke volume index
      (SVI), and right atrial pressure were independently associated with death or lung
      transplantation, adjusted for age, sex, and type of PAH. Pulmonary arterial
      compliance did not independently predict outcomes at baseline or during follow
      up. The adjusted hazard ratio for SVI was 1.28 (95% confidence interval, 1.11
      1.49; P<0.01) per 10-mL/m2 decrease and for right atrial pressure was 1.05 (95%
      confidence interval, 1.02-1.09; P<0.01) per 1-mm Hg increase. Among patients who
      had 2 (n=355) or 3 (n=193) low-risk prognostic features at follow-up, including a
      cardiac index >=2.5 L.min-1.m-2, 6-minute walk distance >440 m, and New York
      Heart Association class I or II functional class, lower SVI was still associated
      with higher rates of death or lung transplantation (P<0.01). CONCLUSIONS: SVI and
      right atrial pressure were the hemodynamic variables that were independently
      associated with death or lung transplantation at first follow-up RHC after
      initial PAH treatment. These findings suggest that the SVI could be a more
      appropriate treatment target than cardiac index in PAH.

PMID- 29070503
TI  - Aerobic exercise training-induced changes in serum C1q/TNF-related protein levels
      are associated with reduced arterial stiffness in middle-aged and older adults.
AB  - Adiponectin regulates endothelial nitric oxide synthase in endothelial cells, and
      body fat loss by aerobic exercise training promotes adiponectin secretion.
      Recently, C1q/tumor necrosis factor-related proteins (CTRPs) have been identified
      as novel adipokines and are paralogs of adiponectin, but the association between
      exercise training-induced reduction of arterial stiffness and circulating CTRPs
      levels remains unclear. This study aimed to clarify whether the reduction of
      arterial stiffness in middle-aged and older adults is associated with the change
      in serum levels of CTRPs induced by exercise training. A total of 52 middle-aged
      and older participants were randomly divided into two groups: a training group (
      n = 26) and a sedentary control group ( n = 26). Participants in the training
      group completed 8 wk of aerobic exercise training (60-70% peak oxygen uptake for
      45 min, 3 days/wk). The reduction of percent whole body fat, abdominal visceral
      fat area, and carotid-femoral pulse-wave velocity (cfPWV) was significantly
      greater in the training group than in the control group ( P < 0.05). Moreover,
      the increase in serum adiponectin, CTRP3, and CTRP5 from baseline to 8 wk was
      significantly higher in the training group compared with the control group ( P <
      0.05). Additionally, the training-induced change in cfPWV was negatively
      correlated with the training-induced change in serum adiponectin, CTRP3, and
      CTRP5 levels ( r = -0.51, r = -0.48, r = -0.42, respectively, P < 0.05), and
      increased plasma nitrite/nitrate level by exercise training was correlated only
      with adiponectin levels ( r = 0.41, P < 0.05). These results suggest that the
      exercise training-induced increase in serum CTRPs levels may be associated with
      the reduction of arterial stiffness in middle-aged and older adults.

PMID- 29070504
TI  - First evidence of nocturnin in fish: two isoforms in goldfish differentially
      regulated by feeding.
AB  - Nocturnin (NOC) is a unique deadenylase with robust rhythmic expression involved
      in the regulation of metabolic processes in mammals. Currently, the possible
      presence of NOC in fish is unknown. This report aimed to identify NOC in a fish
      model, the goldfish ( Carassius auratus), and to study the possible regulation of
      its expression by feeding. Two partial-length cDNAs of 293 and 223 bp, named
      nocturnin-a ( noc-a) and nocturnin-b ( noc-b), were identified and found to be
      highly conserved among vertebrates. Both mRNAs show a similar widespread
      distribution in central and peripheral tissues, with higher levels detected for
      noc-a compared with noc-b. The periprandial expression profile revealed that noc
      a mRNAs rise sharply after a meal in hypothalamus, intestinal bulb, and liver,
      whereas almost no changes were observed for noc-b. Food deprivation was found to
      exert opposite effects on the expression of both NOCs (generally inhibitory for
      noc-a, and stimulatory for noc-b) in the three mentioned tissues. A single meal
      after a 48-h food deprivation period reversed (totally or partially) the fasting
      induced decreases in noc-a transcripts in all studied tissues and the increases
      in noc-b expression in the intestinal bulb. Together, this study offers the first
      report of NOC in fish and shows a high dependence of its expression on feeding
      and nutritional status. The differential responses to feeding of the two NOCs
      raise the possibility that they might be underlying different physiological
      mechanisms (e.g., food intake, lipid mobilization, energy homeostasis) in fish.

PMID- 29070506
TI  - The 2017 New Investigator Review Awards.

PMID- 29070505
TI  - Interindividual variability in muscle sympathetic responses to static handgrip in
      young men: evidence for sympathetic responder types?
AB  - Negative and positive muscle sympathetic nerve activity (MSNA) responders have
      been observed during mental stress. We hypothesized that similar MSNA response
      patterns could be identified during the first minute of static handgrip and
      contribute to the interindividual variability throughout exercise. Supine
      measurements of multiunit MSNA (microneurography) and continuous blood pressure
      (Finometer) were recorded in 29 young healthy men during the first (HG1) and
      second (HG2) minute of static handgrip (30% maximal voluntary contraction) and
      subsequent postexercise circulatory occlusion (PECO). Responders were identified
      on the basis of differences from the typical error of baseline total MSNA: 7
      negative, 12 positive, and 10 nonresponse patterns. Positive responders
      demonstrated larger total MSNA responses during HG1 ( P < 0.01) and HG2 ( P <
      0.0001); however, the increases in blood pressure throughout handgrip exercise
      were similar between all groups, as were the changes in heart rate, stroke
      volume, cardiac output, total vascular conductance, and respiration (all P >
      0.05). Comparing negative and positive responders, total MSNA responses were
      similar during PECO ( P = 0.17) but opposite from HG2 to PECO (?40 +/- 46 vs. ?
      21 +/- 62%, P = 0.04). Negative responders also had a shorter time-to-peak
      diastolic blood pressure during HG1 (20 +/- 20 vs. 44 +/- 14 s, P < 0.001). Total
      MSNA responses during HG1 were associated with responses to PECO ( r = 0.39, P <
      0.05), the change from HG2 to PECO ( r = -0.49, P < 0.01), and diastolic blood
      pressure time to peak ( r = 0.50, P < 0.01). Overall, MSNA response patterns
      during the first minute of static handgrip contribute to interindividual
      variability and appear to be influenced by differences in central command, muscle
      metaboreflex activation, and rate of loading of the arterial baroreflex.

PMID- 29070507
TI  - Prescribing antibiotics to hospitalised patients increases the risk of
      Clostridium difficile infection for the next bed occupant.

PMID- 29070508
TI  - Coordinated Functional Divergence of Genes after Genome Duplication in
      Arabidopsis thaliana.
AB  - Gene and genome duplications have been rampant during the evolution of flowering
      plants. Unlike small-scale gene duplications, whole-genome duplications (WGDs)
      copy entire pathways or networks, and as such create the unique situation in
      which such duplicated pathways or networks could evolve novel functionality
      through the coordinated sub- or neofunctionalization of its constituent genes.
      Here, we describe a remarkable case of coordinated gene expression divergence
      following WGDs in Arabidopsis thaliana We identified a set of 92 homoeologous
      gene pairs that all show a similar pattern of tissue-specific gene expression
      divergence following WGD, with one homoeolog showing predominant expression in
      aerial tissues and the other homoeolog showing biased expression in tip-growth
      tissues. We provide evidence that this pattern of gene expression divergence
      seems to involve genes with a role in cell polarity and that likely function in
      the maintenance of cell wall integrity. Following WGD, many of these duplicated
      genes evolved separate functions through subfunctionalization in
      growth/development and stress response. Uncoupling these processes through genome
      duplications likely provided important adaptations with respect to growth and
      morphogenesis and defense against biotic and abiotic stress.

PMID- 29070509
TI  - Light Inhibits COP1-Mediated Degradation of ICE Transcription Factors to Induce
      Stomatal Development in Arabidopsis.
AB  - Stomata are epidermal openings that facilitate plant-atmosphere gas exchange
      during photosynthesis, respiration, and water evaporation. Stomatal
      differentiation and patterning are spatially and temporally regulated by the
      master regulators SPEECHLESS (SPCH), MUTE, and FAMA, which constitute a central
      gene regulatory network along with Inducer of CBF Expression (ICE) transcription
      factors for this developmental process. Stomatal development is also profoundly
      influenced by environmental conditions, such as light, temperature, and humidity.
      Light induces stomatal development, and various photoreceptors modulate this
      response. However, it is unknown how light is functionally linked with the master
      regulatory network. Here, we demonstrate that, under dark conditions, the E3
      ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) degrades ICE proteins
      through ubiquitination pathways in leaf abaxial epidermal cells in Arabidopsis
      thaliana Accordingly, the ICE proteins accumulate in the nuclei of leaf abaxial
      epidermal cells in COP1-defective mutants, which constitutively produce stomata.
      Notably, light in the blue, red, and far-red wavelength ranges suppresses the
      COP1-mediated degradation of the ICE proteins to induce stomatal development.
      These observations indicate that light is directly linked with the ICE-directed
      signaling module, via the COP1-mediated protein surveillance system, in the
      modulation of stomatal development.

PMID- 29070511
TI  - Metformin in gestational diabetes mellitus: predictors of poor response.
AB  - OBJECTIVE: Metformin can be regarded as a first-line treatment in gestational
      diabetes mellitus (GDM) due to its safety and effectiveness. However, a
      proportion of women do not achieve adequate glycemic control with metformin
      alone. We aim to identify predictors of this poor response to metformin. DESIGN
      AND METHODS: Retrospective multicentre cohort study of women with GDM who started
      metformin as first-line treatment. The assessed cohort was divided into a
      metformin group and metformin plus insulin group. Biometric and demographic
      characteristics, glycemic control data, obstetric, neonatal and postpartum
      outcomes were compared between groups and analysed in order to identify
      predictors of poor response to metformin. Data were analysed using STATA, version
      13.1. RESULTS: Of the 388 women enrolled in the study, 135 (34.8%) required
      additional insulin therapy to achieve the glycemic targets. Higher age (aOR: 1.08
      (1.03-1.13), P = 0.003), higher pre-pregnancy body mass index (BMI) (1.06 (1.02
      1.10), P = 0.003) and earlier introduction of metformin (0.89 (0.85-0.94), P <
      0.001) were independent predictors for insulin supplementation. Regarding all the
      analysed outcomes, only cesarean delivery rates and postpartum glucose levels
      were higher in women requiring insulin supplementation. CONCLUSIONS: Although
      almost 35% of women did not achieve adequate glycemic control with metformin,
      insulin supplementation was not associated with poor neonatal outcomes. Higher
      age, higher pre-pregnancy BMI and earlier introduction of metformin could be used
      as predictors of poor response to metformin.

PMID- 29070510
TI  - Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on
      Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index
      of Atherosclerosis.
AB  - The objectives of the study were to determine the contribution, in mice, of
      members of the flavin-containing monooxygenase (FMO) family to the production of
      trimethylamine (TMA) N-oxide (TMAO), a potential proatherogenic molecule, and
      whether under normal dietary conditions differences in TMAO production were
      associated with changes in plasma cholesterol concentration or with an index of
      atherosclerosis (Als). Concentrations of urinary TMA and TMAO and plasma
      cholesterol were measured in 10-week-old male and female C57BL/6J and CD-1 mice
      and in mouse lines deficient in various Fmo genes (Fmo1-/- , 2-/- , 4-/- , and
      Fmo5-/- ). In female mice most TMA N-oxygenation was catalyzed by FMO3, but in
      both genders 11%-12% of TMA was converted to TMAO by FMO1. Gender-, Fmo genotype
      , and strain-related differences in TMAO production were accompanied by opposite
      effects on plasma cholesterol concentration. Plasma cholesterol was negatively,
      but weakly, correlated with TMAO production and urinary TMAO concentration. Fmo
      genotype had no effect on Als. There was no correlation between Als and either
      TMAO production or urinary TMAO concentration. Our results indicate that under
      normal dietary conditions TMAO does not increase plasma cholesterol or act as a
      proatherogenic molecule.

PMID- 29070512
TI  - Identifying and treating subclinical thyroid dysfunction in pregnancy: emerging
      controversies.
AB  - Thyroid hormones are essential for an adequate growth and development of the
      fetus. In addition to the classical association between maternal hypothyroidism
      and neurological impairment in the progeny, other adverse reproductive events
      have been associated with maternal thyroid dysfunction including infertility,
      miscarriage and preterm delivery. Although all scientific societies endorse the
      treatment of overt hypothyroidism; the management and/or treatment of subclinical
      hypothyroidism, hypothyroxinemia or antithyroid antibody-positive women should be
      considered with caution. Important trials have found no clear benefit of
      treatment of subclinical hypothyroidism in terms of cognitive outcomes; however,
      other interventional studies appear to reduce some of the obstetric and perinatal
      complications. As a result, the dilemma between universal screening or selective
      screening of women at high risk of thyroid dysfunction during pregnancy remains
      unresolved. Despite this, levothyroxine is also now regularly prescribed by
      gynaecologists and centres for reproductive medicine. In this context, there is
      increasing concern regarding the risk of over diagnosis and subsequent potential
      overtreatment. Taken together, we need to reconsider how thyroid dysfunction
      should be identified in pregnant women and highlight the arguments for and
      against the use of levothyroxine in obstetric practices. Our main findings: the
      mismatch between the guidelines recommendations and the use of LT4 in clinical
      settings as well as the disparity of criteria between scientific societies from
      different medical specialties. In conclusion, it is essential to reach agreements
      between both endocrinologists and obstetricians.

PMID- 29070513
TI  - Simplifying care: when is the treatment burden too much for patients living in
      poverty?

PMID- 29070514
TI  - Phosphorylation of Arabidopsis MAP Kinase Phosphatase 1 (MKP1) Is Required for
      PAMP Responses and Resistance against Bacteria.
AB  - Plants perceive potential pathogens via the recognition of pathogen-associated
      molecular patterns (PAMPs) by surface-localized pattern recognition receptors,
      which initiates a series of intracellular responses that ultimately limit
      bacterial growth. PAMP responses include changes in intracellular protein
      phosphorylation, including the activation of mitogen-activated protein kinase
      (MAPK) cascades. MAP kinase phosphatases (MKPs), such as Arabidopsis (Arabidopsis
      thaliana) MKP1, are important negative regulators of MAPKs and play a crucial
      role in controlling the intensity and duration of MAPK activation during innate
      immune signaling. As such, the mkp1 mutant lacking MKP1 displays enhanced PAMP
      responses and resistance against the virulent bacterium Pseudomonas syringae pv
      tomato DC3000. Previous in vitro studies showed that MKP1 can be phosphorylated
      and activated by MPK6, suggesting that phosphorylation may be an important
      mechanism for regulating MKP1. We found that MKP1 was phosphorylated during PAMP
      elicitation and that phosphorylation stabilized the protein, resulting in protein
      accumulation after elicitation. MKP1 also can be stabilized by the proteasome
      inhibitor MG132, suggesting that MKP1 is constitutively degraded through the
      proteasome in the resting state. In addition, we investigated the role of MKP1
      posttranslational regulation in plant defense by testing whether phenotypes of
      the mkp1 Arabidopsis mutant could be complemented by expressing phosphorylation
      site mutations of MKP1. The phosphorylation of MKP1 was found to be required for
      some, but not all, of MKP1's functions in PAMP responses and defense against
      bacteria. Together, our results provide insight into the roles of phosphorylation
      in the regulation of MKP1 during PAMP signaling and resistance to bacteria.

PMID- 29070517
TI  - Host-Induced Gene Silencing of the MAPKK Gene PsFUZ7 Confers Stable Resistance to
      Wheat Stripe Rust.
AB  - RNA interference (RNAi) is a powerful genetic tool to accelerate research in
      plant biotechnology and control biotic stresses by manipulating target gene
      expression. However, the potential of RNAi in wheat to efficiently and durably
      control the devastating stripe rust fungus Puccinia striiformis f. sp. tritici
      (Pst) remained largely under explored so far. To address this issue, we generated
      transgenic wheat (Triticum aestivum) lines expressing dsRNA targeting PsFUZ7
      transcripts of Pst We analyzed expression of PsFUZ7 and related genes, and
      resistance traits of the transgenic wheat lines. We show that PsFUZ7 is an
      important pathogenicity factor that regulates infection and development of Pst A
      PsFUZ7 RNAi construct stably expressed in two independent transgenic wheat lines
      confers strong resistance to PstPst hyphal development is strongly restricted,
      and necrosis of plant cells in resistance responses was significantly induced. We
      conclude that trafficking of RNA molecules from wheat plants to Pst may lead to a
      complex molecular dialogue between wheat and the rust pathogen. Moreover, we
      confirm the RNAi-based crop protection approaches can be used, to our knowledge,
      as a novel control strategy against rust pathogens in wheat.

PMID- 29070515
TI  - Flavan-3-ols Are an Effective Chemical Defense against Rust Infection.
AB  - Phenolic secondary metabolites are often thought to protect plants against attack
      by microbes, but their role in defense against pathogen infection in woody plants
      has not been investigated comprehensively. We studied the biosynthesis,
      occurrence, and antifungal activity of flavan-3-ols in black poplar (Populus
      nigra), which include both monomers, such as catechin, and oligomers, known as
      proanthocyanidins (PAs). We identified and biochemically characterized three
      leucoanthocyanidin reductases and two anthocyanidin reductases from P. nigra
      involved in catalyzing the last steps of flavan-3-ol biosynthesis, leading to the
      formation of catechin [2,3-trans-(+)-flavan-3-ol] and epicatechin [2,3-cis-(-)
      flavan-3-ol], respectively. Poplar trees that were inoculated with the biotrophic
      rust fungus (Melampsora larici-populina) accumulated higher amounts of catechin
      and PAs than uninfected trees. The de novo-synthesized catechin and PAs in the
      rust-infected poplar leaves accumulated significantly at the site of fungal
      infection in the lower epidermis. In planta concentrations of these compounds
      strongly inhibited rust spore germination and reduced hyphal growth. Poplar
      genotypes with constitutively higher levels of catechin and PAs as well as hybrid
      aspen (Populus tremula * Populus alba) overexpressing the MYB134 transcription
      factor were more resistant to rust infection. Silencing PnMYB134, on the other
      hand, decreased flavan-3-ol biosynthesis and increased susceptibility to rust
      infection. Taken together, our data indicate that catechin and PAs are effective
      antifungal defenses in poplar against foliar rust infection.

PMID- 29070516
TI  - Regular Motifs in Xylan Modulate Molecular Flexibility and Interactions with
      Cellulose Surfaces.
AB  - Xylan is tightly associated with cellulose and lignin in secondary plant cell
      walls, contributing to its rigidity and structural integrity in vascular plants.
      However, the molecular features and the nanoscale forces that control the
      interactions among cellulose microfibrils, hemicelluloses, and lignin are still
      not well understood. Here, we combine comprehensive mass spectrometric glycan
      sequencing and molecular dynamics simulations to elucidate the substitution
      pattern in softwood xylans and to investigate the effect of distinct
      intramolecular motifs on xylan conformation and on the interaction with cellulose
      surfaces in Norway spruce (Picea abies). We confirm the presence of motifs with
      evenly spaced glycosyl decorations on the xylan backbone, together with minor
      motifs with consecutive glucuronation. These domains are differently enriched in
      xylan fractions extracted by alkali and subcritical water, which indicates their
      preferential positioning in the secondary plant cell wall ultrastructure. The
      flexibility of the 3-fold screw conformation of xylan in solution is enhanced by
      the presence of arabinofuranosyl decorations. Additionally, molecular dynamic
      simulations suggest that the glycosyl substitutions in xylan are not only
      sterically tolerated by the cellulose surfaces but that they increase the
      affinity for cellulose and favor the stabilization of the 2-fold screw
      conformation. This effect is more significant for the hydrophobic surface
      compared with the hydrophilic ones, which demonstrates the importance of nonpolar
      driving forces on the structural integrity of secondary plant cell walls. These
      novel molecular insights contribute to an improved understanding of the
      supramolecular architecture of plant secondary cell walls and have fundamental
      implications for overcoming lignocellulose recalcitrance and for the design of
      advanced wood-based materials.

PMID- 29070518
TI  - Digoxin enhances radiation response in radioresistant A549 cells by reducing
      protein phosphatase 2A.
AB  - Protein phosphatase 2A (PP2A) is a ubiquitous multifunctional enzyme usually
      known as a tumor suppressor. Recent studies have reported that although
      inhibition of PP2A leads to acceleration of cell growth, it also induces damaged
      cells to pass through the cell cycle and renders them sensitive to radiotherapy.
      Here, we investigated the radiosensitizing effects of digoxin as a PP2A inhibitor
      in two non-small-cell lung cancer (NSCLC) cell types (H460 and A549) with
      differential sensitivity to radiation. Digoxin inhibited the proliferation of
      H460 and A549 cells in a dose-dependent fashion and was especially effective on
      radioresistant A549 cells. Interestingly, the radiosensitizing effect of digoxin
      was only present in the radioresistant A549 cells and xenografts. The combination
      of digoxin and ionizing radiation (IR) significantly reduced clonogenic survival
      and xenograft tumor growth (P<0.001), compared with IR alone. Digoxin suppressed
      PP2A protein expression and prevented IR-induced PP2A expression in A549 cells.
      Digoxin treatment combined with IR allowed the damaged cell to progress through
      the cell cycle via suppression of cell cycle-related proteins (p53, cyclin D1,
      cyclin B1, CDK4, and p-cdc2). Moreover, digoxin enhanced IR-induced DNA damage
      through reduction in levels of repair proteins and elevation of p-ATM foci
      formation up to 24 h (P<0.001). In conclusion, digoxin has a novel function as a
      PP2A inhibitor, and combined with IR produces a synergistic effect on
      radiosensitizing cells, thereby indicating a potentially promising therapeutic
      approach to radioresistant lung cancer treatment.

PMID- 29070519
TI  - The mechanism of all-trans retinoic acid in the regulation of apelin expression
      in vascular endothelial cells.
AB  - The apelin gene can promote vascular endothelial cell (VEC) proliferation,
      migration, and angiogenesis. However, the molecular mechanism for regulation of
      the apelin gene is still unknown. Real-time PCR and Western blotting analysis
      were employed to detect the effect of all-trans retinoic acid (ATRA) in up
      regulating apelin expression in human umbilical vein endothelial cells (HUVECs).
      Furthermore, the in vivo study also indicated that ATRA could increase apelin
      expression in balloon-injured arteries of rats, which is consistent with the
      results from the cultured HUVECs. To ensure whether retinoic acid receptor (RAR)
      alpha (RARalpha) could be induced by ATRA in regulating apelin, the expression of
      RARalpha was tested with a siRNA method to knock down RARalpha or adenovirus
      vector infection to overexpress RARalpha. The results showed that ATRA could up
      regulate apelin expression time- and dose- dependently in HUVECs. ATRA could
      induce a RARalpha increase; however, the expression of RARbeta and RARgamma were
      unchanged. The blocking of RARalpha signaling reduced the response of apelin to
      ATRA when HUVECs were treated with RARalpha antagonists (Ro 41-5253) or the use
      of siRNA against RARalpha (si-RARalpha) knockdown RARalpha expression before
      using ATRA. In addition, induction of RARalpha overexpression by infection with
      pAd-GFP-RARalpha further increased the induction of apelin by ATRA. These results
      suggested that ATRA up-regulated apelin expression by promoting RARalpha
      signaling.

PMID- 29070520
TI  - Folic acid inhibits nasopharyngeal cancer cell proliferation and invasion via
      activation of FRalpha/ERK1/2/TSLC1 pathway.
AB  - Folic acid (FA), which is necessary for normal cell division of mammals, has been
      implicated to be involved in many tumors. Dietary FA intake has been reported to
      be associated with a lower risk of nasopharyngeal cancer (NPC). However, the
      molecular mechanisms of FA in NPC cells remain unclear. In the present study, we
      found that FA treatment dose dependently inhibited the proliferation, invasion
      and migration of NPC cells, via folate receptor alpha (FRalpha). We further found
      that FA, bound to FRalpha, induced the activation of MEK/ERK1/2, and increased
      the expressions of TSLC1 and E-cadherin. Moreover, blocking of ERK1/2 activation
      attenuated FA-mediated increase in TSLC1 expression. In addition, knockdown of
      TSLC1 abolished the FA-mediated inhibition of cell proliferation, invasion and
      migration, and suppressed the FA-mediated increase oinE-cadherin expression in
      NPC cells. Taken together, our data suggest that FA treatment inhibits NPC cell
      proliferation and invasion via activation of FRalpha/ERK1/2/ TSLC1 signaling
      pathway. Therefore, FA could be explored as a therapeutic drug for the treatment
      of NPC, and TSLC1 may act as a tumor suppressor in NPC.

PMID- 29070521
TI  - Diminished stress resistance and defective adaptive homeostasis in age-related
      diseases.
AB  - Adaptive homeostasis is defined as the transient expansion or contraction of the
      homeostatic range following exposure to subtoxic, non-damaging, signaling
      molecules or events, or the removal or cessation of such molecules or events
      (Mol. Aspects Med. (2016) 49, 1-7). Adaptive homeostasis allows us to transiently
      adapt (and then de-adapt) to fluctuating levels of internal and external
      stressors. The ability to cope with transient changes in internal and external
      environmental stress, however, diminishes with age. Declining adaptive
      homeostasis may make older people more susceptible to many diseases. Chronic
      oxidative stress and defective protein homeostasis (proteostasis) are two major
      factors associated with the etiology of age-related disorders. In the present
      paper, we review the contribution of impaired responses to oxidative stress and
      defective adaptive homeostasis in the development of age-associated diseases.

PMID- 29070523
TI  - Sepsis-Associated AKI.

PMID- 29070522
TI  - Left Ventricular Assist Devices and the Kidney.
AB  - Left ventricular assist devices (LVADs) are common and implantation carries risk
      of AKI. LVADs are used as a bridge to heart transplantation or as destination
      therapy. Patients with refractory heart failure that develop chronic cardiorenal
      syndrome and CKD often improve after LVAD placement. Nevertheless, reversibility
      of CKD is hard to predict. After LVAD placement, significant GFR increases may be
      followed by a late return to near baseline GFR levels, and in some patients, a
      decline in GFR. In this review, we discuss changes in GFR after LVAD placement,
      the incidence of AKI and associated mortality after LVAD placement, the
      management of AKI requiring RRT, and lastly, we review salient features about
      cardiorenal syndrome learned from the LVAD experience. In light of the growing
      number of patients using LVADs as a destination therapy, it is important to
      understand the effect of these devices on the kidney. Additional research and
      long-term data are required to better understand the relationship between the
      LVAD and the kidney.

PMID- 29070524
TI  - Engineering oxidative stability in human hemoglobin based on the Hb providence
      (betaK82D) mutation and genetic cross-linking.
AB  - Previous work suggested that hemoglobin (Hb) tetramer formation slows
      autoxidation and hemin loss and that the naturally occurring mutant, Hb
      Providence (HbProv; betaK82D), is much more resistant to degradation by H2O2 We
      have examined systematically the effects of genetic cross-linking of Hb tetramers
      with and without the HbProv mutation on autoxidation, hemin loss, and reactions
      with H2O2, using native HbA and various wild-type recombinant Hbs as controls.
      Genetically cross-linked Hb Presbyterian (betaN108K) was also examined as an
      example of a low oxygen affinity tetramer. Our conclusions are: (a) at low
      concentrations, all the cross-linked tetramers show smaller rates of autoxidation
      and hemin loss than HbA, which can dissociate into much less stable dimers and
      (b) the HbProv betaK82D mutation confers more resistance to degradation by H2O2,
      by markedly inhibiting oxidation of the beta93 cysteine side chain, particularly
      in cross-linked tetramers and even in the presence of the destabilizing Hb
      Presbyterian mutation. These results show that cross-linking and the betaK82D
      mutation do enhance the resistance of Hb to oxidative degradation, a critical
      element in the design of a safe and effective oxygen therapeutic.

PMID- 29070525
TI  - PTEN Is Fundamental for Elimination of Leukemia Stem Cells Mediated by GSK126
      Targeting EZH2 in Chronic Myelogenous Leukemia.
AB  - Purpose: Leukemia stem cells (LSCs) are an important source of tyrosine kinase
      inhibitor resistance and disease relapse in patients with chronic myelogenous
      leukemia (CML). Targeting LSCs may be an attractive strategy to override this
      thorny problem. Given that EZH2 was overexpressed in primary CML CD34+ cells, our
      purpose in this study was to evaluate the effects of targeting EZH2 on CML LSCs
      and clarify its underlying mechanism.Experimental Design: Human primary CML CD34+
      cells and retrovirally BCR-ABL-driven CML mouse models were employed to evaluate
      the effects of suppression of EZH2 by GSK126- or EZH2-specific shRNA in vitro and
      in vivo Recruitment of EZH2 and H3K27me3 on the promoter of tumor-suppressor gene
      PTEN in CML cells was measured by chromatin immunoprecipitation assay.Results:
      Our results showed that pharmacologic inhibition of EZH2 by GSK126 not only
      elicited apoptosis and restricted cell growth in CML bulk leukemia cells, but
      also decreased LSCs in CML CD34+ cells while sparing those from normal bone
      marrow CD34+ cells. Suppression of EZH2 by GSK126 or specific shRNA prolonged
      survival of CML mice and reduced the number of LSCs in mice. EZH2 knockdown
      resulted in elevation of PTEN and led to impaired recruitment of EZH2 and
      H3K27me3 on the promoter of PTEN gene. The effect of EZH2 knockdown in the CML
      mice was at least partially reversed by PTEN knockdown.Conclusions: These
      findings improve the understanding of the epigenetic regulation of stemness in
      CML LSCs and warrant clinical trial of GSK126 in refractory patients with CML.
      Clin Cancer Res; 24(1); 145-57. (c)2017 AACR.

PMID- 29070526
TI  - Circulating Tumor Cells from Different Vascular Sites Exhibit Spatial
      Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical
      Significance in Hepatocellular Carcinoma.
AB  - Purpose: The spatial heterogeneity of phenotypic and molecular characteristics of
      CTCs within the circulatory system remains unclear. Herein, we mapped the
      distribution and characterized biological features of CTCs along the
      transportation route in hepatocellular carcinoma (HCC).Experimental Design: In 73
      localized HCC patients, blood was drawn from peripheral vein (PV), peripheral
      artery (PA), hepatic veins (HV), infrahepatic inferior vena cava (IHIVC), and
      portal vein (PoV) before tumor resection. Epithelial and mesenchymal transition
      (EMT) phenotype in CTCs were analyzed by a 4-channel immunofluorescence
      CellSearch assay and microfluidic quantitative RT-PCR. The clinical significance
      of CTCs from different vascular sites was evaluated.Results: The CTC number and
      size gradient between tumor efferent vessels and postpulmonary peripheral vessels
      was marked. Tracking the fate of CTC clusters revealed that CTCs displayed an
      aggregated-singular-aggregated manner of spreading. Single-cell characterization
      demonstrated that EMT status of CTCs was heterogeneous across different vascular
      compartments. CTCs were predominantly epithelial at release, but switched to EMT
      activated phenotype during hematogeneous transit via Smad2 and beta-catenin
      related signaling pathways. EMT activation in primary tumor correlated with total
      CTC number at HV, rather than epithelial or EMT-activated subsets of CTCs. Follow
      up analysis suggested that CTC and circulating tumor microemboli burden in
      hepatic veins and peripheral circulation prognosticated postoperative lung
      metastasis and intrahepatic recurrence, respectively.Conclusions: The current
      data suggested that a profound spatial heterogeneity in cellular distribution and
      biological features existed among CTCs during circulation. Multivascular
      measurement of CTCs could help to reveal novel mechanisms of metastasis and
      facilitate prediction of postoperative relapse or metastasis pattern in HCC. Clin
      Cancer Res; 24(3); 547-59. (c)2017 AACR.

PMID- 29070528
TI  - The Legacy of CVI.
AB  - Clinical and Vaccine Immunology (CVI) will merge with the American Society for
      Microbiology (ASM) open-access journal mSphere in January 2018. We commemorate
      this transition by exploring the history of CVI and that of its predecessor,
      Clinical and Diagnostic Laboratory Immunology (CDLI), and by acknowledging their
      contributors. Research on vaccines, clinical immunology, and clinical diagnostic
      immunology published through mSphere will be available without restrictions to an
      ever-larger audience, which will expedite progress in the field. ASM remains
      committed to supporting its members and the research community by facilitating
      the dissemination of scientific knowledge in these important areas.

PMID- 29070527
TI  - Extracellular Vesicles Released by Cardiomyocytes in a Doxorubicin-Induced
      Cardiac Injury Mouse Model Contain Protein Biomarkers of Early Cardiac Injury.
AB  - Purpose: Cardiac injury is a major cause of death in cancer survivors, and
      biomarkers for it are detectable only after tissue injury has occurred.
      Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be
      detected in the blood. Here, we evaluate the potential of using circulating EVs
      as early diagnostic markers for long-term cardiac injury.Experimental Design:
      Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified
      serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs
      released after DOX treatment, and investigated the alteration of EV
      content.Results: Treatment with DOX caused a significant increase in circulating
      EVs (DOX_EV) compared with saline-treated controls. DOX_EVs exhibited a higher
      level of 4-hydroxynonenal adducted proteins, a lipid peroxidation product linked
      to DOX-induced cardiotoxicity. Proteomic profiling of DOX_EVs revealed the
      distinctive presence of brain/heart, muscle, and liver isoforms of glycogen
      phosphorylase (GP), and their origins were verified to be heart, skeletal muscle,
      and liver, respectively. The presence of brain/heart GP (PYGB) in DOX_EVs
      correlated with a reduction of PYGB in heart, but not brain tissues. Manganese
      superoxide dismutase (MnSOD) overexpression, as well as pretreatment with
      cardioprotective agents and MnSOD mimetics, resulted in a reduction of EV
      associated PYGB in mice treated with DOX. Kinetic studies indicated that EVs
      containing PYGB were released prior to the rise of cardiac troponin in the blood
      after DOX treatment, suggesting that PYGB is an early indicator of cardiac
      injury.Conclusions: EVs containing PYGB are an early and sensitive biomarker of
      cardiac injury. Clin Cancer Res; 24(7); 1644-53. (c)2017 AACRSee related
      commentary by Zhu and Gius, p. 1516.

PMID- 29070529
TI  - Anticitrullinated protein/peptide antibody multiplexing defines an extended group
      of ACPA-positive rheumatoid arthritis patients with distinct genetic and
      environmental determinants.
AB  - INTRODUCTION: The second generation anticycliccitrullinated peptide (anti-CCP2)
      assay detects the majority but not all anticitrullinated protein/peptide
      antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated
      with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay
      to detect multiple specific ACPA, we have investigated the fine specificity of
      individual ACPA responses and the biological impact of additional ACPA reactivity
      among anti-CCP2-negative patients. METHODS: We investigated 2825 patients with RA
      and 551 healthy controls with full data on anti-CCP2, HLA-DRB1* alleles and
      smoking history concerning reactivity against 16 citrullinated peptides and
      arginine control peptides with a multiplex array. RESULTS: The prevalence of the
      16 ACPA specificities ranged from 9% to 58%. When reactivity to arginine peptides
      was subtracted, the mean diagnostic sensitivity increased by 3.2% with maintained
      98% specificity. Of the anti-CCP2-negative patients, 16% were found to be ACPA
      positive. All ACPA specificities associated with SE, and all but one with
      smoking. Correction for arginine reactivity also conveyed a stronger association
      with SE for 13/16 peptides. Importantly, when all ACPA specificities were
      analysed together, SE and smoking associated with RA in synergy among ACPA
      positive, but not among ACPA-negative subjects also in the anti-CCP2-negative
      subset. CONCLUSIONS: Multiplexing detects an enlarged group of ACPA-positive but
      anti-CCP2-negative patients with genetic and environmental attributes previously
      assigned to anti-CCP2-positive patients. The individual correction for arginine
      peptide reactivity confers both higher diagnostic sensitivity and stronger
      association to SE than gross ACPA measurement.

PMID- 29070530
TI  - The histone demethylase Jumonji domain-containing protein 3 (JMJD3) regulates
      fibroblast activation in systemic sclerosis.
AB  - OBJECTIVES: Systemic sclerosis (SSc) fibroblasts remain activated even in the
      absence of exogenous stimuli. Epigenetic alterations are thought to play a role
      for this endogenous activation. Trimethylation of histone H3 on lysine 27
      (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and
      ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a
      therapeutically targetable manner. The aim of this study was to explore H3K27me3
      demethylases as potential targets for the treatment of fibrosis. METHODS: JMJD3
      was inactivated by small interfering RNA-mediated knockdown and by
      pharmacological inhibition with GSKJ4. The effects of targeted inactivation of
      JMJD3 were analysed in cultured fibroblasts and in the murine models of bleomycin
      induced and topoisomerase-I (topoI)-induced fibrosis. H3K27me3 at the FRA2
      promoter was analysed by ChIP. RESULTS: The expression of JMJD3, but not of UTX,
      was increased in fibroblasts in SSc skin and in experimental fibrosis in a
      transforming growth factor beta (TGFbeta)-dependent manner. Inactivation of JMJD3
      reversed the activated fibroblast phenotype in SSc fibroblasts and prevented the
      activation of healthy dermal fibroblasts by TGFbeta. Pharmacological inhibition
      of JMJD3 ameliorated bleomycin-induced and topoI-induced fibrosis in well
      tolerated doses. JMJD3 regulated fibroblast activation in a FRA2-dependent
      manner: Inactivation of JMJD3 reduced the expression of FRA2 by inducing
      accumulation of H3K27me3 at the FRA2 promoter. Moreover, the antifibrotic effects
      of JMJD3 inhibition were reduced on knockdown of FRA2. CONCLUSION: We present
      first evidence for a deregulation of JMJD3 in SSc. JMJD3 modulates fibroblast
      activation by regulating the levels of H3K27me3 at the promoter of FRA2. Targeted
      inhibition of JMJD3 limits the aberrant activation of SSc fibroblasts and exerts
      antifibrotic effects in two murine models.

PMID- 29070532
TI  - Bringing Back the Term "Intersex".

PMID- 29070534
TI  - A Gut Feeling About Developmental Programming Mechanisms: Trimethylamine-N-Oxide
      May Enhance Atherosclerosis in Offspring of Hypercholesterolemic Mice.

PMID- 29070533
TI  - International Variation in Asthma and Bronchiolitis Guidelines.
AB  - BACKGROUND AND OBJECTIVES: Guideline recommendations for the same clinical
      condition may vary. The purpose of this study was to determine the degree of
      agreement among comparable asthma and bronchiolitis treatment recommendations
      from guidelines. METHODS: National and international guidelines were searched by
      using guideline databases (eg, National Guidelines Clearinghouse: December 16-17,
      2014, and January 9, 2015). Guideline recommendations were categorized as (1)
      recommend, (2) optionally recommend, (3) abstain from recommending, (4) recommend
      against a treatment, and (5) not addressed by the guideline. The degree of
      agreement between recommendations was evaluated by using an unweighted and
      weighted kappa score. Pairwise comparisons of the guidelines were evaluated
      similarly. RESULTS: There were 7 guidelines for asthma and 4 guidelines for
      bronchiolitis. For asthma, there were 166 recommendation topics, with 69
      recommendation topics given in >=2 guidelines. For bronchiolitis, there were 46
      recommendation topics, with 21 recommendation topics provided in >=2 guidelines.
      The overall kappa for asthma was 0.03, both unweighted (95% confidence interval
      [CI]: -0.01 to 0.07) and weighted (95% CI: -0.01 to 0.10); for bronchiolitis, it
      was 0.32 unweighted (95% CI: 0.16 to 0.52) and 0.15 weighted (95% CI: -0.01 to
      0.5). CONCLUSIONS: Less agreement was found in national and international
      guidelines for asthma than for bronchiolitis. Additional studies are needed to
      determine if differences are based on patient preferences and values and economic
      considerations or if other recommendation-level, guideline-level, and condition
      level factors are driving these differences.

PMID- 29070531
TI  - Affinity maturation shapes the function of agonistic antibodies to
      peptidylarginine deiminase type 4 in rheumatoid arthritis.
AB  - OBJECTIVES: The citrullinating enzyme peptidylarginine deiminase type 4 (PAD4) is
      the target of a polyclonal group of autoantibodies in patients with rheumatoid
      arthritis (RA). A subgroup of such antibodies, initially identified by cross
      reactivity with peptidylarginine deiminase type 3 (PAD3), is strongly associated
      with progression of radiographic joint damage and interstitial lung disease and
      has the unique ability to activate PAD4. The features of these antibodies in
      terms of their T cell-dependent origin, genetic characteristics and effect of
      individual antibody specificities on PAD4 function remain to be defined. METHODS:
      We used PAD4 tagged with the monomeric fluorescent protein mWasabi to isolate
      PAD4-specific memory B cells from anti-PAD4 positive patients with RA and applied
      single cell cloning technologies to obtain monoclonal antibodies. RESULTS: Among
      44 single B cells, we cloned five antibodies with PAD4-activating properties.
      Sequence analysis, germline reversion experiments and antigen specificity assays
      suggested that autoantibodies to PAD4 are not polyreactive and arise from PAD4
      reactive precursors. Somatic mutations increase the agonistic activity of these
      antibodies at low calcium concentrations by facilitating their interaction with
      structural epitopes that modulate calcium-binding site 5 in PAD4. CONCLUSIONS:
      PAD4-activating antibodies directly amplify a key process in disease
      pathogenesis, making them unique among other autoantibodies in RA. Understanding
      the molecular basis for their functionality may inform the design of future PAD4
      inhibitors.

PMID- 29070535
TI  - Vitamin D and Risk of Cardiovascular Disease.

PMID- 29070536
TI  - Further Evidence Supporting a Protective Role of Transforming Growth Factor-beta
      (TGFbeta) in Aortic Aneurysm and Dissection.

PMID- 29070537
TI  - Beyond Impressions: How Altered Shear Stress Connects Hypoxic Signaling to
      Endothelial Inflammation.

PMID- 29070540
TI  - Insight Into the Editor: Nigel Mackman, PhD.

PMID- 29070538
TI  - New Mouse Model of Abdominal Aortic Aneurysm: Put Out to Expand.

PMID- 29070539
TI  - Cardiovascular Immunotherapy and the Role of Imaging.

PMID- 29070541
TI  - Gaps in evidence regarding iron deficiency anemia in pregnant women and young
      children: summary of US Preventive Services Task Force recommendations.
AB  - The US Preventive Services Task Force (USPSTF) makes recommendations to primary
      care providers regarding preventive services for asymptomatic patients.
      Recommendations are based on the scientific evidence that the delivery of the
      preventive service leads to improvements in meaningful patient outcomes. After a
      review of the available evidence, the USPSTF found insufficient evidence to
      recommend routine iron supplementation for pregnant women or routine screening
      for iron deficiency anemia in pregnant women or young children. The USPSTF
      identified a critical evidence gap that is related to whether changing
      hematologic indexes in otherwise asymptomatic pregnant women or in infants within
      populations who are reflective of the United States leads to an improvement in
      maternal or child health outcomes. Future research opportunities are described to
      address these important evidence gaps.

PMID- 29070542
TI  - Iron homeostasis during pregnancy.
AB  - During pregnancy, iron needs to increase substantially to support fetoplacental
      development and maternal adaptation to pregnancy. To meet these iron
      requirements, both dietary iron absorption and the mobilization of iron from
      stores increase, a mechanism that is in large part dependent on the iron
      regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin
      concentrations are suppressed in the second and third trimesters, thereby
      facilitating an increased supply of iron into the circulation. The mechanism of
      maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by
      the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears
      to be preserved during pregnancy. Inappropriately increased maternal hepcidin
      during pregnancy can compromise the iron availability for placental transfer and
      impair the efficacy of iron supplementation. The role of fetal hepcidin in the
      regulation of placental iron transfer still remains to be characterized. This
      review summarizes the current understanding and addresses the gaps in knowledge
      about gestational changes in hematologic and iron variables and regulatory
      aspects of maternal, fetal, and placental iron homeostasis.

PMID- 29070543
TI  - Iron status in pregnant women and women of reproductive age in Europe.
AB  - Understanding the iron status in pregnant women in Europe provides a foundation
      for considering the role of iron screening and supplementation. However,
      available reports and studies have used different approaches that challenge the
      devising of overall summaries. Moreover, data on pregnant women are limited, and
      thus, data on women of reproductive age provide useful background information
      including baseline iron stores in pregnant women. This review considered data
      that are available from >15 European countries including national surveys and
      relevant clinical studies. In European women of reproductive age, median or
      geometric mean serum ferritin (SF) concentrations were estimated at 26-38 MUg/L.
      Approximately 40-55% of this population had small or depleted iron stores (i.e.,
      SF concentration <=30 MUg/L), and 45-60% of this population had apparently
      replete iron stores. The prevalence of iron deficiency (ID) and iron deficiency
      anemia (IDA) was 10-32% and 2-5%, respectively, depending on the cutoffs used.
      Approximately 20-35% of European women of reproductive age had sufficient iron
      stores (SF concentration >70 MUg/L) to complete a pregnancy without supplementary
      iron. During pregnancy, European women in controlled supplementation trials who
      were not receiving iron supplements displayed increasing prevalences of ID and
      IDA during pregnancy, which peaked in the middle to late third trimester.
      Available evidence has suggested that, in gestational weeks 32-39, the median or
      geometric mean SF concentrations were 6-21 MUg/L, and prevalences of ID and IDA
      were 28-85% and 21-35%, respectively. Women who were taking iron supplements had
      higher iron status and lower prevalences of ID and IDA, which were dependent on
      the dose of iron and compliance. The data suggest that, in Europe, the iron
      status of reproductive-aged women varies by region and worsens in pregnancy
      without iron supplementation.

PMID- 29070544
TI  - Excess iron intake as a factor in growth, infections, and development of infants
      and young children.
AB  - The provision of iron via supplementation or the fortification of foods has been
      shown to be effective in preventing and treating iron deficiency and iron
      deficiency anemia in infants and young children. However, iron is a pro-oxidative
      element and can have negative effects on biological systems even at moderate
      amounts. An increasing number of studies have reported adverse effects of iron
      that was given to infants and young-children populations who initially were iron
      replete. These effects include decreased growth (both linear growth and weight),
      increased illness (usually diarrhea), interactions with other trace elements such
      as copper and zinc, altered gut microbiota to more pathogenic bacteria, increased
      inflammatory markers, and impaired cognitive and motor development. If these
      results can be confirmed by larger and well-controlled studies, it may have
      considerable programmatic implications (e.g., the necessity to screen for iron
      status before interventions to exclude iron-replete individuals). A lack of
      understanding of the mechanisms underlying these adverse outcomes limits our
      ability to modify present supplementation and fortification strategies. This
      review summarizes studies on the adverse effects of iron on various outcomes;
      suggests possible mechanisms that may explain these observations, which are
      usually made in clinical studies and intervention trials; and gives examples from
      animal models and in vitro studies. With a better understanding of these
      mechanisms, it may be possible to find novel ways of providing iron in a form
      that causes fewer or no adverse effects even when subjects are iron replete.
      However, it is apparent that our understanding is limited, and research in this
      area is urgently needed.

PMID- 29070545
TI  - Laboratory methodologies for indicators of iron status: strengths, limitations,
      and analytical challenges.
AB  - Biochemical assessment of iron status relies on serum-based indicators, such as
      serum ferritin (SF), transferrin saturation, and soluble transferrin receptor
      (sTfR), as well as erythrocyte protoporphyrin. These indicators present
      challenges for clinical practice and national nutrition surveys, and often iron
      status interpretation is based on the combination of several indicators. The
      diagnosis of iron deficiency (ID) through SF concentration, the most commonly
      used indicator, is complicated by concomitant inflammation. sTfR concentration is
      an indicator of functional ID that is not an acute-phase reactant, but challenges
      in its interpretation arise because of the lack of assay standardization, common
      reference ranges, and common cutoffs. It is unclear which indicators are best
      suited to assess excess iron status. The value of hepcidin, non-transferrin-bound
      iron, and reticulocyte indexes is being explored in research settings. Serum
      based indicators are generally measured on fully automated clinical analyzers
      available in most hospitals. Although international reference materials have been
      available for years, the standardization of immunoassays is complicated by the
      heterogeneity of antibodies used and the absence of physicochemical reference
      methods to establish "true" concentrations. From 1988 to 2006, the assessment of
      iron status in NHANES was based on the multi-indicator ferritin model. However,
      the model did not indicate the severity of ID and produced categorical estimates.
      More recently, iron status assessment in NHANES has used the total body iron
      stores (TBI) model, in which the log ratio of sTfR to SF is assessed. Together,
      sTfR and SF concentrations cover the full range of iron status. The TBI model
      better predicts the absence of bone marrow iron than SF concentration alone, and
      TBI can be analyzed as a continuous variable. Additional consideration of
      methodologies, interpretation of indicators, and analytic standardization is
      important for further improvements in iron status assessment.

PMID- 29070546
TI  - Impact of chronic and acute inflammation on extra- and intracellular iron
      homeostasis.
AB  - Inflammation has a major impact on iron homeostasis. This review focuses on acute
      and chronic inflammation as it affects iron trafficking and, as a result, the
      availability of this essential micronutrient to the host. In situations of
      microbial infection, not only the host is affected but also the offending
      microorganisms, which, in general, not only require iron for their own growth but
      have evolved mechanisms to obtain it from the infected host. Key players in
      mammalian iron trafficking include several types of cells important to iron
      acquisition, homeostasis, and hematopoiesis (enterocytes, hepatocytes,
      macrophages, hematopoietic cells, and in the case of pregnancy, placental
      syncytiotrophoblast cells) and several forms of chaperone proteins, including,
      for nonheme iron, the transport protein transferrin and the intracellular iron
      storage protein ferritin, and for heme iron, the chaperone proteins haptoglobin
      and hemopexin. Additional key players are the cell membrane-associated iron
      transporters, particularly ferroportin (FPN), the only protein known to modulate
      iron export from cells, and finally, the iron-regulatory hormone hepcidin, which,
      in addition to having antibacterial activity, regulates the functions of FPN.
      Interestingly, the impact of infection on iron homeostasis differs among
      pathogens whose mode of infection is mainly intracellular or extracellular.
      Understanding how inflammation affects each of these processes may be crucial for
      understanding how inflammation affects iron status, indicators of iron
      sufficiency, and iron supplementation during inflammation and how it may
      potentially result in a beneficial or detrimental impact on the host.

PMID- 29070547
TI  - Emerging understanding and measurement of plasma volume expansion in pregnancy.
AB  - Plasma volume expansion is an important component of a successful pregnancy. The
      failure of maternal plasma volume expansion has been implicated in adverse
      obstetric outcomes such as pre-eclampsia, fetal growth restriction, and preterm
      birth. Altered iron homeostasis and elevated maternal hemoglobin concentrations
      have also been associated with adverse pregnancy outcomes; limited data have
      suggested that these effects may be mediated by inadequate plasma volume
      expansion. In addition, it has been noted that pregnant, obese women, compared
      with lean subjects, have decreased plasma volume expansion along with impaired
      iron homeostasis and increased inflammation. Current estimates of plasma volume
      expansion are outdated and do not necessarily reflect contemporary obstetric
      populations. Moreover, the validation of clinically applicable methods of plasma
      volume determination as well as enhanced methodologies should be a priority.
      Further study is needed to characterize diminished plasma volume expansion during
      pregnancy and to understand the potential role of impaired iron homeostasis and
      inflammation in adverse obstetric outcomes, especially in obese women.

PMID- 29070548
TI  - Excess iron: considerations related to development and early growth.
AB  - What effects might arise from early life exposures to high iron? This review
      considers the specific effects of high iron on the brain, stem cells, and the
      process of erythropoiesis and identifies gaps in our knowledge of what molecular
      damage may be incurred by oxidative stress that is imparted by high iron status
      in early life. Specific areas to enhance research on this topic include the
      following: longitudinal behavioral studies of children to test associations
      between iron exposures and mood, emotion, cognition, and memory; animal studies
      to determine epigenetic changes that reprogram brain development and metabolic
      changes in early life that could be followed through the life course; and the
      establishment of human epigenetic markers of iron exposures and oxidative stress
      that could be monitored for early origins of adult chronic diseases. In addition,
      efforts to understand how iron exposure influences stem cell biology could be
      enhanced by establishing platforms to collect biological specimens, including
      umbilical cord blood and amniotic fluid, to be made available to the research
      community. At the molecular level, there is a need to better understand stress
      erythropoiesis and changes in iron metabolism during pregnancy and development,
      especially with respect to regulatory control under high iron conditions that
      might promote ineffective erythropoiesis and iron-loading anemia. These
      investigations should focus not only on factors such as hepcidin and
      erythroferrone but should also include newly identified interactions between
      transferrin receptor-2 and the erythropoietin receptor. Finally, despite our
      understanding that several key micronutrients (e.g., vitamin A, copper,
      manganese, and zinc) support iron's function in erythropoiesis, how these
      nutrients interact remains, to our knowledge, unknown. It is necessary to
      consider many factors when formulating recommendations on iron supplementation.

PMID- 29070549
TI  - Iron status of young children in Europe.
AB  - Iron deficiency (ID) is common in young children aged 6-36 mo. Although the
      hazards associated with iron deficiency anemia (IDA) are well known, concerns
      about risks associated with excess iron intake in young children are emerging. To
      characterize iron status in Europe, we describe the prevalence of ID, IDA, iron
      repletion, and excess stores with the use of published data from a systematic
      review on iron intake and deficiency rates, combined with other selected iron
      status data in young European children. Various definitions for ID and IDA were
      applied across studies. ID prevalence varied depending on socioeconomic status
      and type of milk fed (i.e., human or cow milk or formula). Without regard to
      these factors, ID was reported in 3-48% of children aged >=12 mo across the
      countries. For 6- to 12-mo-old infants, based on studies that did not
      differentiate these factors, ID prevalence was 4-18%. IDA was <5% in most studies
      in Northern and Western Europe but was considerably higher in Eastern Europe (9
      50%). According to current iron status data from a sample of healthy Western
      European children aged 12-36 mo, 69% were iron replete, and the 97.5th percentile
      for serum ferritin (SF) was 64.3 MUg/L. In another sample, 79% of 24-mo-old
      children were iron replete, and the 97.5th percentile for SF was 57.3 MUg/L.
      Average iron intake in most countries studied was close to or below the UK's
      Recommended Dietary Allowance. In conclusion, even in healthy European children
      aged 6-36 mo, ID is still common. In Western European populations for whom data
      were available, approximately three-quarters of children were found to be iron
      replete, and excess iron stores (SF >100 MUg/L) did not appear to be a concern.
      Consensus on the definitions of iron repletion and excess stores, as well as on
      ID and IDA, is needed.

PMID- 29070550
TI  - Iron assessment to protect the developing brain.
AB  - Iron deficiency (ID) before the age of 3 y can lead to long-term neurological
      deficits despite prompt diagnosis of ID anemia (IDA) by screening of hemoglobin
      concentrations followed by iron treatment. Furthermore, pre- or nonanemic ID
      alters neurobehavioral function and is 3 times more common than IDA in toddlers.
      Given the global prevalence of ID and the enormous societal cost of developmental
      disabilities across the life span, better methods are needed to detect the risk
      of inadequate concentrations of iron for brain development (i.e., brain tissue
      ID) before dysfunction occurs and to monitor its amelioration after diagnosis and
      treatment. The current screening and treatment strategy for IDA fails to achieve
      this goal for 3 reasons. First, anemia is the final state in iron depletion.
      Thus, the developing brain is already iron deficient when IDA is diagnosed owing
      to the prioritization of available iron to red blood cells over all other tissues
      during negative iron balance in development. Second, brain ID, independently of
      IDA, is responsible for long-term neurological deficits. Thus, starting iron
      treatment after the onset of IDA is less effective than prevention. Multiple
      studies in humans and animal models show that post hoc treatment strategies do
      not reliably prevent ID-induced neurological deficits. Third, most currently used
      indexes of ID are population statistical cutoffs for either hematologic or iron
      status but are not bioindicators of brain ID and brain dysfunction in children.
      Furthermore, their relation to brain iron status is not known. To protect the
      developing brain, there is a need to generate serum measures that index brain
      dysfunction in the preanemic stage of ID, assess the ability of standard iron
      indicators to detect ID-induced brain dysfunction, and evaluate the efficacy of
      early iron treatment in preventing ID-induced brain dysfunction.

PMID- 29070551
TI  - Current understanding of iron homeostasis.
AB  - Iron is an essential trace element, but it is also toxic in excess, and thus
      mammals have developed elegant mechanisms for keeping both cellular and whole
      body iron concentrations within the optimal physiologic range. In the diet, iron
      is either sequestered within heme or in various nonheme forms. Although the
      absorption of heme iron is poorly understood, nonheme iron is transported across
      the apical membrane of the intestinal enterocyte by divalent metal-ion
      transporter 1 (DMT1) and is exported into the circulation via ferroportin 1
      (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around
      the body to sites of utilization with the erythroid marrow having particularly
      high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1
      on the surface of most body cells, and after endocytosis of the complex, iron
      enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used
      for metabolic functions, stored within cytosolic ferritin, or exported from the
      cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory
      proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption
      and iron export from the tissues into the plasma are regulated by the liver
      derived peptide hepcidin. When tissue iron demands are high, hepcidin
      concentrations are low and vice versa. Too little or too much iron can have
      important clinical consequences. Most iron deficiency reflects an inadequate
      supply of iron in the diet, whereas iron excess is usually associated with
      hereditary disorders. These disorders include various forms of hemochromatosis,
      which are characterized by inadequate hepcidin production and, thus, increased
      dietary iron intake, and iron-loading anemias whereby both increased iron
      absorption and transfusion therapy contribute to the iron overload. Despite major
      recent advances, much remains to be learned about iron physiology and
      pathophysiology.

PMID- 29070552
TI  - The effects of iron fortification and supplementation on the gut microbiome and
      diarrhea in infants and children: a review.
AB  - In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA)
      is common, and many complementary foods are low in bioavailable iron. In-home
      fortification of complementary foods using iron-containing micronutrient powders
      (MNPs) and oral iron supplementation are both effective strategies to increase
      iron intakes and reduce IDA at this age. However, these interventions produce
      large increases in colonic iron because the absorption of their high iron dose
      (>=12.5 mg) is typically <20%. We reviewed studies in infants and young children
      on the effects of iron supplements and iron fortification with MNPs on the gut
      microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly
      increase diarrhea risk, and in vitro and in vivo studies have suggested that this
      occurs because increases in colonic iron adversely affect the gut microbiome in
      that they decrease abundances of beneficial barrier commensal gut bacteria (e.g.,
      bifidobacteria and lactobacilli) and increase the abundance of enterobacteria
      including entropathogenic Escherichia coli These changes are associated with
      increased gut inflammation. Therefore, safer formulations of iron-containing
      supplements and MNPs are needed. To improve MNP safety, the iron dose of these
      formulations should be reduced while maximizing absorption to retain efficacy.
      Also, the addition of prebiotics to MNPs is a promising approach to mitigate the
      adverse effects of iron on the infant gut.

PMID- 29070553
TI  - Introduction to workshop on iron screening and supplementation in iron-replete
      pregnant women and young children.
AB  - The NIH Office of Dietary Supplements convened a public workshop on iron
      screening and supplementation in iron-replete pregnant women and young children
      in 2016 in Bethesda, Maryland. The starting point for the workshop was the recent
      reports from the US Preventive Services Task Force concluding that there was
      insufficient evidence to evaluate the benefits and harms associated with iron
      screening and routine supplementation among asymptomatic pregnant women and young
      children (6-24 mo old) in the United States. The goal of the workshop was to
      explore and refine understanding about the existing knowledge gaps and research
      needs associated with these preventive services for these groups. Given the focus
      on the United States, planning for the workshop took into account the higher iron
      status in the United States compared with developing countries and, in turn,
      included a focus on iron-replete individuals consistent with the U-shaped risk
      curve for nutrient-health relations. Topic areas included adaptations in iron
      homeostasis associated with pregnancy and young childhood, the impact of
      inflammation, measurement of iron status, current estimates of iron status for
      pregnant women and young children in the United States and in Europe, and
      emerging evidence suggesting adverse effects associated with iron supplementation
      of iron-replete individuals. A crosscutting dialogue conducted at the close of
      the workshop formed the basis for a workshop summary that specified evidence gaps
      and research needs in a range of areas centered on the relation of these
      adaptations of iron homeostasis with the response to and risk from iron
      supplementation as well as the need for indicators informative of the full
      continuum of iron status and based on health outcomes, not just erythropoiesis.

PMID- 29070554
TI  - Dietary iron intake, iron status, and gestational diabetes.
AB  - Pregnant women are particularly vulnerable to iron deficiency and related adverse
      pregnancy outcomes and, as such, are routinely recommended for iron
      supplementation. Emerging evidence from both animal and population-based studies,
      however, has raised potential concerns because significant associations have been
      observed between greater iron stores and disturbances in glucose metabolism,
      including increased risk of type 2 diabetes among nonpregnant individuals. Yet,
      the evidence is uncertain regarding the role of iron in the development of
      gestational diabetes mellitus (GDM), a common pregnancy complication which has
      short-term and long-term adverse health ramifications for both women and their
      children. In this review, we critically and systematically evaluate available
      data examining the risk of GDM associated with dietary iron, iron
      supplementation, and iron status as measured by blood concentrations of several
      indicators. We also discuss major methodologic concerns regarding the available
      epidemiologic studies on iron and GDM.

PMID- 29070556
TI  - Integrating themes, evidence gaps, and research needs identified by workshop on
      iron screening and supplementation in iron-replete pregnant women and young
      children.
AB  - This report addresses the evidence and the uncertainties, knowledge gaps, and
      research needs identified by participants at the NIH workshop related to iron
      screening and routine iron supplementation of largely iron-replete pregnant women
      and young children (6-24 mo) in developed countries. The workshop presentations
      and panel discussions focused on current understanding and knowledge gaps related
      to iron homeostasis, measurement of and evidence for iron status, and emerging
      concerns about supplementing iron-replete members of these vulnerable
      populations. Four integrating themes emerged across workshop presentations and
      discussion and centered on 1) physiologic or developmental adaptations of iron
      homeostasis to pregnancy and early infancy, respectively, and their implications,
      2) improvement of the assessment of iron status across the full continuum from
      iron deficiency anemia to iron deficiency to iron replete to iron excess, 3) the
      linkage of iron status with health outcomes beyond hematologic outcomes, and 4)
      the balance of benefit and harm of iron supplementation of iron-replete pregnant
      women and young children. Research that addresses these themes in the context of
      the full continuum of iron status is needed to inform approaches to the balancing
      of benefits and harms of screening and routine supplementation.

PMID- 29070555
TI  - Ethnic and genetic factors of iron status in women of reproductive age.
AB  - Background: African Americans are at increased risk of iron deficiency (ID) but
      also have higher serum ferritin (SF) concentrations than those of the general
      population. The Hemochromatosis and Iron Overload Screening (HEIRS) Study was a
      multicenter study of ethnically diverse participants that tested for the
      hemochromatosis (HFE) C282Y genotype and iron status.Objective: We sought to
      determine the prevalence and predictors of ID (SF concentration <=15 MUg/L) and
      elevated iron stores (SF concentration >300 MUg/L) in HEIRS women of reproductive
      age (25-44 y).Design: The HEIRS Study was a cross-sectional study of iron status
      and HFE mutations in primary care patients at 5 centers in the United States and
      Canada. We analyzed data for women of reproductive age according to whether or
      not they were pregnant or breastfeeding at the time of the study.Results: ID was
      present in 12.5% of 20,080 nonpregnant and nonbreastfeeding women compared with
      19.2% of 1962 pregnant or breastfeeding women (P < 0.001). Asian American
      ethnicity (OR <=0.9; P <= 0.049) and HFE C282Y (OR <=0.84; P <= 0.060) were
      independently associated with a decreased risk of ID in nonpregnant and
      nonbreastfeeding women and in pregnant or breastfeeding women. Hispanic ethnicity
      (OR: 1.8; P < 0.001) and African American ethnicity (OR: 1.6; P < 0.001) were
      associated with an increased risk of ID in nonpregnant and nonbreastfeeding
      women. Elevated iron stores were shown in 1.7% of nonpregnant and
      nonbreastfeeding women compared with 0.7% of pregnant or breastfeeding women (P =
      0.001). HFE C282Y homozygosity had the most marked independent association with
      elevated iron stores in nonpregnant and nonbreastfeeding women and in pregnant or
      breastfeeding women (OR >49.0; P < 0.001), but African American ethnicity was
      also associated with increased iron stores in both groups of women (OR >2.0; P <
      0.001). Asian American ethnicity (OR: 1.8; P = 0.001) and HFE C282Y
      heterozygosity (OR: 1.9; P = 0.003) were associated with increased iron stores in
      nonpregnant and nonbreastfeeding women.Conclusions: Both ID and elevated iron
      stores are present in women of reproductive age and are influenced by ethnicity
      and HFE C282Y. Efforts to optimize iron status should keep these findings in
      view. This study was registered at clinicaltrials.gov as NCT03276247.

PMID- 29070558
TI  - Harmonization of blood-based indicators of iron status: making the hard work
      matter.
AB  - Blood-based indicators that are used in the assessment of iron status are assumed
      to be accurate. In practice, inaccuracies in these measurements exist and stem
      from bias and variability. For example, the analytic variability of serum
      ferritin measurements across laboratories is very high (>15%), which increases
      the rate of misclassification in clinical and epidemiologic studies. The
      procedures that are used in laboratory medicine to minimize bias and variability
      could be used effectively in clinical research studies, particularly in the
      evaluation of iron deficiency and its associated anemia in pregnancy and early
      childhood and in characterizing states of iron repletion and excess. The
      harmonization and standardization of traditional and novel bioindicators of iron
      status will allow results from clinical studies to be more meaningfully
      translated into clinical practice by providing a firm foundation for clinical
      laboratories to set appropriate cutoffs. In addition, proficiency testing
      monitors the performance of the methods over time. It is important that measures
      of iron status be evaluated, validated, and performed in a manner that is
      consistent with standard procedures in laboratory medicine.

PMID- 29070557
TI  - Iron status of North American pregnant women: an update on longitudinal data and
      gaps in knowledge from the United States and Canada.
AB  - Pregnant women are particularly vulnerable to iron deficiency due to the high
      iron demands of pregnancy. To avoid the adverse birth outcomes that are
      associated with maternal iron deficiency anemia, both Canada and the United
      States recommend universal iron supplementation for pregnant women. Although the
      benefits of iron supplementation in anemic women are well recognized,
      insufficient data are currently available on the maternal and neonatal benefits
      and harms of universal iron supplementation in developed countries as evidenced
      by the recent conclusions of the US Preventive Services Task Force on the need
      for further data that address existing gaps. As part of an effort to evaluate the
      impact of the current North American prenatal iron supplementation policy, this
      review highlights the lack of national data on longitudinal changes in iron
      status in pregnant North American women, emphasizes possible limitations with the
      original longitudinal hemoglobin data used to inform the current CDC reference
      hemoglobin values, and presents additional normative data from recent
      longitudinal research studies of iron status in North American pregnant women.
      Further longitudinal data in North American pregnant women are needed to help
      identify those who may benefit most from supplementation as well as to help
      determine whether there are adverse effects of iron supplementation in iron
      replete women.

PMID- 29070559
TI  - Iron status of toddlers, nonpregnant females, and pregnant females in the United
      States.
AB  - Background: Total-body iron stores (TBI), which are calculated from serum
      ferritin and soluble transferrin receptor concentrations, can be used to assess
      the iron status of populations in the United States.Objective: This analysis,
      developed to support workshop discussions, describes the distribution of TBI and
      the prevalence of iron deficiency (ID) and ID anemia (IDA) among toddlers,
      nonpregnant females, and pregnant females.Design: We analyzed data from NHANES;
      toddlers aged 12-23 mo (NHANES 2003-2010), nonpregnant females aged 15-49 y
      (NHANES 2007-2010), and pregnant females aged 12-49 y (NHANES 1999-2010). We used
      SAS survey procedures to plot distributions of TBI and produce prevalence
      estimates of ID and IDA for each target population. All analyses were weighted to
      account for the complex survey design.Results: According to these data, ID
      prevalences (+/- SEs) were 15.1% +/- 1.7%, 10.4% +/- 0.5%, and 16.3% +/- 1.3% in
      toddlers, nonpregnant females, and pregnant females, respectively. ID prevalence
      in pregnant females increased significantly with each trimester (5.3% +/- 1.5%,
      12.7% +/- 2.3%, and 27.5% +/- 3.5% in the first, second, and third trimesters,
      respectively). Racial disparities in the prevalence of ID among both nonpregnant
      and pregnant females exist, with Mexican American and non-Hispanic black females
      at greater risk of ID than non-Hispanic white females. IDA prevalence was 5.0% +/
      0.4% and 2.6% +/- 0.7% in nonpregnant and pregnant females,
      respectively.Conclusions: Available nationally representative data suggest that
      ID and IDA remain a concern in the United States. Estimates of iron-replete
      status cannot be made at this time in the absence of established cutoffs for iron
      repletion based on TBI. The study was registered at clinicaltrials.gov as
      NCT03274726.

PMID- 29070560
TI  - Serum ferritin as an indicator of iron status: what do we need to know?
AB  - Determination of iron status in pregnancy and in young children is essential for
      both clinical and public health practice. Clinical diagnosis of iron deficiency
      (ID) through sampling of bone marrow to identify the absence of body iron stores
      is impractical in most cases. Serum ferritin (SF) concentrations are the most
      commonly deployed indicator for determining ID, and low SF concentrations reflect
      a state of iron depletion. However, there is considerable variation in SF cutoffs
      recommended by different expert groups to diagnose ID. Moreover, the cutoffs used
      in different clinical laboratories are heterogeneous. There are few studies of
      diagnostic test accuracy to establish the sensitivity and specificity of SF
      compared with key gold standards (such as absent bone marrow iron stores,
      increased intestinal iron absorption, and hemoglobin response to SF) among
      noninflamed, outpatient populations. The limited data available suggest the
      commonly recommended SF cutoff of <15 MUg/L is a specific but not sensitive
      cutoff, although evidence is limited. Data from women during pregnancy or from
      young children are especially uncommon. Most data are from studies conducted >30
      y ago, do not reflect ethnic or geographic diversity, and were performed in an
      era for which laboratory methods no longer reflect present practice. Future
      studies to define the appropriate SF cutoffs are urgently needed and would also
      provide an opportunity to compare this indicator with other established and
      emerging iron indexes. In addition, future work would benefit from a focus on
      elucidating cutoffs and indexes relevant to iron adequacy.

PMID- 29070561
TI  - Development of iron homeostasis in infants and young children.
AB  - Healthy, term, breastfed infants usually have adequate iron stores that, together
      with the small amount of iron that is contributed by breast milk, make them iron
      sufficient until >=6 mo of age. The appropriate concentration of iron in infant
      formula to achieve iron sufficiency is more controversial. Infants who are fed
      formula with varying concentrations of iron generally achieve sufficiency with
      iron concentrations of 2 mg/L (i.e., with iron status that is similar to that of
      breastfed infants at 6 mo of age). Regardless of the feeding choice, infants'
      capacity to regulate iron homeostasis is important but less well understood than
      the regulation of iron absorption in adults, which is inverse to iron status and
      strongly upregulated or downregulated. Infants who were given daily iron drops
      compared with a placebo from 4 to 6 mo of age had similar increases in hemoglobin
      concentrations. In addition, isotope studies have shown no difference in iron
      absorption between infants with high or low hemoglobin concentrations at 6 mo of
      age. Together, these findings suggest a lack of homeostatic regulation of iron
      homeostasis in young infants. However, at 9 mo of age, homeostatic regulatory
      capacity has developed although, to our knowledge, its extent is not known.
      Studies in suckling rat pups showed similar results with no capacity to regulate
      iron homeostasis at 10 d of age when fully nursing, but such capacity occurred at
      20 d of age when pups were partially weaned. The major iron transporters in the
      small intestine divalent metal-ion transporter 1 (DMT1) and ferroportin were not
      affected by pup iron status at 10 d of age but were strongly affected by iron
      status at 20 d of age. Thus, mechanisms that regulate iron homeostasis are
      developed at the time of weaning. Overall, studies in human infants and
      experimental animals suggest that iron homeostasis is absent or limited early in
      infancy largely because of a lack of regulation of the iron transporters DMT1 and
      ferroportin.

PMID- 29070562
TI  - Comparison of global nutrient profiling systems for restricting the commercial
      marketing of foods and beverages of low nutritional quality to children in
      Canada.
AB  - Background: The Canadian government recently committed to introduce legislation
      to restrict the commercial marketing of unhealthy foods and beverages to
      children.Objective: We compared the degree of strictness and agreement between
      nutrient profile (NP) models relevant to marketing restrictions by applying them
      in the Canadian context.Design: With the use of data from the University of
      Toronto 2013 Food Label Information Program (n = 15,342 prepackaged foods), 4 NP
      models were evaluated: the Food Standards Australia New Zealand-Nutrient
      Profiling Scoring Criterion (FSANZ-NPSC), the WHO Regional Office for Europe
      (EURO) model, the Pan American Health Organization (PAHO) model, and a modified
      version of the PAHO model (Modified-PAHO), which did not consider the extent of
      food processing because the application of this characteristic was prone to
      ambiguity. The number and proportion of foods that would be eligible for
      marketing to children was calculated with the use of each model, overall and by
      food category.Results: The Modified-PAHO and PAHO models would permit only 9.8%
      (95% CI: 9.4%, 10.3%) and 15.8% (95% CI: 15.3%, 16.4%) of foods, respectively,
      followed by the EURO model [29.8% (95% CI: 29.0%, 30.5%)]. In contrast, the FSANZ
      NPSC would consider almost half of prepackaged foods as eligible for marketing to
      children [49.0% (95% CI: 48.2%, 49.8%)]. Cross-classification analyses showed
      that only 8.1% of foods would be eligible based on all models (e.g., most pastas
      without sauce). Subanalyses showed that each model would be more stringent when
      evaluating food items that specifically target children on their package (n =
      747; from 1.9% of foods eligible under Modified-PAHO to 24.2% under FSANZ
      NPSC).Conclusions: The degree of strictness and agreement vary greatly between NP
      models applicable to marketing restrictions. The discrepancies between models
      highlight the importance for policy makers to carefully evaluate the
      characteristics underlying such models when trying to identify a suitable model
      to underpin regulations restricting the marketing of unhealthy foods to children.

PMID- 29070563
TI  - Low serum omega-3 and omega-6 polyunsaturated fatty acids and other metabolites
      are associated with poor linear growth in young children from rural Malawi.
AB  - Background: Stunting affects ~25% of children <5 y of age and is associated with
      impaired cognitive and motor development and increased morbidity and mortality.
      The pathogenesis of stunting is poorly understood.Objective: The purpose of this
      study was to identify altered metabolic pathways associated with child
      stunting.Design: We measured 677 serum metabolites using liquid chromatography
      tandem mass spectrometry in a cross-sectional study of 400 Malawian children aged
      12-59 mo, of whom 62% were stunted.Results: A low height-for-age z score (HAZ)
      was associated with lower serum concentrations of 1) omega-3 (n-3) and omega-6 (n
      6) polyunsaturated fatty acids (PUFAs), 2) sulfated neurosteroids, which play a
      role in brain development, 3) carnitine, a conditionally essential nutrient with
      an important role in the carnitine shuttle for the metabolism of fatty acids and
      energy production, and 4) gamma-glutamyl amino acids, which represent an altered
      gamma-glutamyl cycle of glutathione metabolism. A low HAZ was associated with
      significantly higher serum concentrations of 5 biomarkers related to cigarette
      smoke exposure.Conclusions: This metabolomics study shows a cross-sectional
      association between stunting and low serum omega-3 and omega-6 long-chain PUFAs,
      which are essential for growth and development; low sulfated neurosteroids, which
      play a role in brain development; low carnitine, which is essential for beta
      oxidation of fatty acids; alterations in glutathione metabolism; and increased
      serum metabolites that are associated with secondhand tobacco smoke exposure.
      This trial was registered at www.controlled-trials.com as ISRCTN14597012.

PMID- 29070564
TI  - No metabolic effects of mustard allyl-isothiocyanate compared with placebo in
      men.
AB  - Background: Induction of nonshivering thermogenesis can be used to influence
      energy balance to prevent or even treat obesity. The pungent component of
      mustard, allyl-isothiocyanate (AITC), activates the extreme cold receptor
      transient receptor potential channel, subfamily A, member 1 and may thus induce
      energy expenditure and metabolic changes.Objective: The objective of our study
      was to evaluate the potential of mustard AITC to induce thermogenesis (primary
      outcome) and alter body temperature, cold and hunger sensations, plasma metabolic
      parameters, and energy intake (secondary outcomes).Design: Energy expenditure in
      mice was measured after subcutaneous injection with vehicle, 1 mg
      norepinephrine/kg, or 5 mg AITC/kg. In our human crossover study, 11 healthy
      subjects were studied under temperature-controlled conditions after an overnight
      fast. After ingestion of 10 g of capsulated mustard or uncapsulated mustard or a
      capsulated placebo mixture, measurements of energy expenditure, substrate
      oxidation, core temperature, cold and hunger scores, and plasma parameters were
      repeated every 30 min during a 150-min period. Subjects were randomly selected
      for the placebo and capsulated mustard intervention; 9 of 11 subjects received
      the uncapsulated mustard as the final intervention because this could not be
      blinded. After the experiments, energy intake was measured with the universal
      eating monitor in a test meal.Results: In mice, AITC administration induced a 32%
      increase in energy expenditure compared with vehicle (17.5 +/- 4.9 J . min-1 .
      mouse-1 compared with 12.5 +/- 1.2 J . min-1 . mouse-1, P = 0.03). Of the 11
      randomly selected participants, 1 was excluded because of intercurrent illness
      after the first visit and 1 withdrew after the second visit. Energy expenditure
      did not increase after ingestion of capsulated or uncapsulated mustard compared
      with placebo. No differences in substrate oxidation, core temperature, cold and
      hunger scores, or plasma parameters were found, nor was the energy intake at the
      end of the experiment different between the 3 conditions.Conclusion: The highest
      tolerable dose of mustard we were able to use did not elicit a relevant
      thermogenic response in humans. This trial was registered at www.controlled
      trials.com as ISRCTN19147515.

PMID- 29070565
TI  - U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron
      supplementation.
AB  - Both iron deficiency (ID) and excess can lead to impaired health status. There is
      substantial evidence of a U-shaped curve between the risk of adverse birth
      outcomes and maternal hemoglobin concentrations during pregnancy; however, it is
      unclear whether those relations are attributable to conditions of low and high
      iron status or to other mechanisms. We summarized current evidence from human
      studies regarding the association between birth outcomes and maternal hemoglobin
      concentrations or iron status. We also reviewed effects of iron supplementation
      on birth outcomes among women at low risk of ID and the potential mechanisms for
      adverse effects of high iron status during pregnancy. Overall, we confirmed a U
      shaped curve for the risk of adverse birth outcomes with maternal hemoglobin
      concentrations, but the relations differ by trimester. For low hemoglobin
      concentrations, the link with adverse outcomes is more evident when hemoglobin
      concentrations are measured in early pregnancy. These relations generally became
      weaker or nonexistent when hemoglobin concentrations are measured in the second
      or third trimesters. Associations between high hemoglobin concentration and
      adverse birth outcomes are evident in all 3 trimesters but evidence is mixed.
      There is less evidence for the associations between maternal iron status and
      adverse birth outcomes. Most studies used serum ferritin (SF) concentrations as
      the indicator of iron status, which makes the interpretation of results
      challenging because SF concentrations increase in response to inflammation or
      infection. The effect of iron supplementation during pregnancy may depend on
      initial iron status. There are several mechanisms through which high iron status
      during pregnancy may have adverse effects on birth outcomes, including oxidative
      stress, increased blood viscosity, and impaired systemic response to inflammation
      and infection. Research is needed to understand the biological processes that
      underlie the U-shaped curves seen in observational studies. Reevaluation of
      cutoffs for hemoglobin concentrations and indicators of iron status during
      pregnancy is also needed.

PMID- 29070566
TI  - A high-glycemic diet is associated with cerebral amyloid burden in cognitively
      normal older adults.
AB  - Background: Little is known about the relation between dietary intake and
      cerebral amyloid accumulation in aging.Objective: We assessed the association of
      dietary glycemic measures with cerebral amyloid burden and cognitive performance
      in cognitively normal older adults.Design: We performed cross-sectional analyses
      relating dietary glycemic measures [adherence to a high-glycemic-load diet
      (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with
      cerebral amyloid burden (measured by florbetapir F-18 positron emission
      tomography) and cognitive performance in 128 cognitively normal older adults who
      provided eligibility screening data for the University of Kansas's Alzheimer's
      Prevention through Exercise (APEX) Study. The study began in November 2013 and is
      currently ongoing.Results: Amyloid was elevated in 26% (n = 33) of participants.
      HGLDiet pattern adherence (P = 0.01), sugar intake (P = 0.03), and carbohydrate
      intake (P = 0.05) were significantly higher in participants with elevated amyloid
      burden. The HGLDiet pattern was positively associated with amyloid burden both
      globally and in all regions of interest independently of age, sex, and education
      (all P <= 0.001). Individual dietary glycemic measures (sugar intake,
      carbohydrate intake, and glycemic load) were also positively associated with
      global amyloid load and nearly all regions of interest independently of age, sex,
      and educational level (P <= 0.05). Cognitive performance was associated only with
      daily sugar intake, with higher sugar consumption associated with poorer global
      cognitive performance (global composite measure and Mini-Mental State
      Examination) and performance on subtests of Digit Symbol, Trail Making Test B,
      and Block Design, controlling for age, sex, and education.Conclusion: A high
      glycemic diet was associated with greater cerebral amyloid burden, which suggests
      diet as a potential modifiable behavior for cerebral amyloid accumulation and
      subsequent Alzheimer disease risk. This trial was registered at
      clinicaltrials.gov as NCT02000583.

PMID- 29070569
TI  - Dexamethasone enhances vasopressin-induced aquaporin-2 gene expression in the
      mpkCCD cells.
AB  - The mouse cortical collecting duct cell (mpkCCD) has been an instrumental cell
      model for studying vasopressin-mediated aquaporin-2 regulation. This cell line
      was first developed by Vandewalle's group from a transgenic mouse carrying the
      transforming SV40 antigens driven by the pyruvate kinase promoter. To immortalize
      the cells, four hormone supplements (dexamethasone, epidermal growth factor,
      insulin, and triiodothyronine) were used to enhance SV40 antigen expression;
      however, these hormones appear to have various effects on aquaporin-2 gene
      expression in the cells. Here, we evaluated the effects of each hormone
      supplement and found that dexamethasone enhanced vasopressin-induced aquaporin-2
      gene expression at both mRNA and protein levels in a dose- and time-dependent
      manner, without affecting mRNA or protein stability. The effects of dexamethasone
      were attributed largely to enhanced aquaporin-2 mRNA transcription in association
      with an enhanced aquaporin-2 promoter activity. Dexamethasone did not affect
      vasopressin-regulated aquaporin-2 phosphorylation and trafficking. In summary, we
      optimized the conditions to enhance vasopressin-induced endogenous aquaporin-2
      gene expression in the mpkCCD cells. By increasing the amount of aquaporin-2
      protein in the cells, our method will facilitate the study of aquaporin-2 cell
      physiology regulated by vasopressin.

PMID- 29070567
TI  - Assessment of iron status in settings of inflammation: challenges and potential
      approaches.
AB  - The determination of iron status is challenging when concomitant infection and
      inflammation are present because of confounding effects of the acute-phase
      response on the interpretation of most iron indicators. This review summarizes
      the effects of inflammation on indicators of iron status and assesses the impact
      of a regression analysis to adjust for inflammation on estimates of iron
      deficiency (ID) in low- and high-infection-burden settings. We overviewed cross
      sectional data from 16 surveys for preschool children (PSC) (n = 29,765) and from
      10 surveys for nonpregnant women of reproductive age (WRA) (n = 25,731) from the
      Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia
      (BRINDA) project. Effects of C-reactive protein (CRP) and alpha1-acid
      glycoprotein (AGP) concentrations on estimates of ID according to serum ferritin
      (SF) (used generically to include plasma ferritin), soluble transferrin receptor
      (sTfR), and total body iron (TBI) were summarized in relation to infection burden
      (in the United States compared with other countries) and population group (PSC
      compared with WRA). Effects of the concentrations of CRP and AGP on SF, sTfR, and
      TBI were generally linear, especially in PSC. Overall, regression correction
      changed the estimated prevalence of ID in PSC by a median of +25 percentage
      points (pps) when SF concentrations were used, by -15 pps when sTfR
      concentrations were used, and by +14 pps when TBI was used; the estimated
      prevalence of ID in WRA changed by a median of +8 pps when SF concentrations were
      used, by -10 pps when sTfR concentrations were used, and by +3 pps when TBI was
      used. In the United States, inflammation correction was done only for CRP
      concentrations because AGP concentrations were not measured; regression
      correction for CRP concentrations increased the estimated prevalence of ID when
      SF concentrations were used by 3 pps in PSC and by 7 pps in WRA. The correction
      of iron-status indicators for inflammation with the use of regression correction
      appears to substantially change estimates of ID prevalence in low- and high
      infection-burden countries. More research is needed to determine the validity of
      inflammation-corrected estimates, their dependence on the etiology of
      inflammation, and their applicability to individual iron-status assessment in
      clinical settings.

PMID- 29070568
TI  - IL-33 deficiency slows cancer growth but does not protect against cisplatin
      induced AKI in mice with cancer.
AB  - The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in
      a 4-wk model of cisplatin-induced AKI in mice with cancer was determined. Mice
      were injected subcutaneously with murine lung cancer cells. Ten days later,
      cisplatin (10 mg.kg-1.wk-1) was administered weekly for 4 wk. The increase in
      kidney IL-33 preceded the AKI and tubular injury, suggesting that IL-33 may play
      a causative role. However, the increase in serum creatinine, blood urea nitrogen,
      serum neutrophil gelatinase-associated lipoprotein, acute tubular necrosis, and
      apoptosis scores in the kidney in cisplatin-induced AKI was the same in wild-type
      and IL-33-deficient mice. There was an increase in kidney expression of pro
      inflammatory cytokines CXCL1 and TNF-alpha, known mediators of cisplatin-induced
      AKI, in IL-33-deficient mice. Surprisingly, tumor weight, tumor volume, and tumor
      growth were significantly decreased in IL-33-deficient mice, and the effect of
      cisplatin on tumors was enhanced in IL-33-deficient mice. As serum IL-33 was
      increased in cisplatin-induced AKI in mice, it was determined whether serum IL-33
      is an early biomarker of AKI in patients undergoing cardiac surgery. Immediate
      postoperative serum IL-33 concentrations were higher in matched AKI cases
      compared with non-AKI controls. In conclusion, even though the cancer grows
      slower in IL-33-deficient mice, the data that IL-33 deficiency does not protect
      against AKI in a clinically relevant model suggest that IL-33 inhibition may not
      be useful to attenuate AKI in patients with cancer. However, serum IL-33 may
      serve as a biomarker of AKI.

PMID- 29070570
TI  - Hypoxia-reoxygenation enhances murine afferent arteriolar vasoconstriction by
      angiotensin II.
AB  - We tested the hypothesis that hypoxia-reoxygenation (H/R) augments vasoreactivity
      to angiotensin II (ANG II). In particular, we compared an in situ live kidney
      slice model with isolated afferent arterioles (C57Bl6 mice) to assess the impact
      of tubules on microvessel response. Hematoxylin and eosin staining was used to
      estimate slice viability. Arterioles in the slices were located by differential
      interference contrast microscopy, and responses to vasoactive substances were
      assessed. Cytosolic calcium transients and NADPH oxidase (NOX) mRNA expression
      were studied in isolated afferent arterioles. SOD activity was measured in live
      slices. Both experimental models were subjected to control and H/R treatment (60
      min). Slices were further analyzed after 30-, 60-, and 90-min hypoxia followed by
      10- or 20-min reoxygenation (H/R). H/R resulted in enhanced necrotic tissue
      damage compared with control conditions. To characterize the slice model, we
      applied ANG II (10-7 M), norepinephrine (NE; 10-5 M), endothelin-1 (ET-1; 10-7
      M), and ATP (10-4 M), reducing the initial diameter to 44.5 +/- 2.8, 50.0 +/-
      2.2, 45.3 +/- 2.6, and 74.1 +/- 1.8%, respectively. H/R significantly increased
      the ANG II response compared with control in live slices and in isolated afferent
      arterioles, although calcium transients remained similar. TEMPOL incubation
      prevented the H/R effect on ANG II responses. H/R significantly increased NOX2
      mRNA expression in isolated arterioles. SOD activity was significantly decreased
      after H/R. Enhanced arteriolar responses after H/R occurred independently from
      the surrounding tissue, indicating no influence of tubules on vascular function
      in this model. The mechanism of increased ANG II response after H/R might be
      increased oxidative stress and increased calcium sensitivity of the contractile
      apparatus.

PMID- 29070571
TI  - Lithium induces aerobic glycolysis and glutaminolysis in collecting duct
      principal cells.
AB  - Lithium, given to bipolar disorder patients, causes nephrogenic diabetes
      insipidus (Li-NDI), a urinary-concentrating defect. Li-NDI occurs due to
      downregulation of principal cell AQP2 expression, which coincides with principal
      cell proliferation. The metabolic effect of lithium on principal cells, however,
      is unknown and investigated here. In earlier studies, we showed that the carbonic
      anhydrase (CA) inhibitor acetazolamide attenuated Li-induced downregulation in
      mouse-collecting duct (mpkCCD) cells. Of the eight CAs present in mpkCCD cells,
      siRNA and drug treatments showed that downregulation of CA9 and to some extent
      CA12 attenuated Li-induced AQP2 downregulation. Moreover, lithium induced cell
      proliferation and increased the secretion of lactate. Lithium also increased
      urinary lactate levels in wild-type mice that developed Li-NDI but not in lithium
      treated mice lacking ENaC, the principal cell entry site for lithium. Inhibition
      of aerobic glycolysis with 2-deoxyglucose (2DG) attenuated lithium-induced AQP2
      downregulation in mpkCCD cells but did not attenuate Li-NDI in mice.
      Interestingly, NMR analysis demonstrated that lithium also increased the urinary
      succinate, fumarate, citrate, and NH4+ levels, which were, in contrast to
      lactate, not decreased by 2DG. Together, our data reveal that lithium induces
      aerobic glycolysis and glutaminolysis in principal cells and that inhibition of
      aerobic glycolysis, but not the glutaminolysis, does not attenuate Li-NDI.

PMID- 29070572
TI  - Glucagon-like peptide-1 analog prevents obesity-related glomerulopathy by
      inhibiting excessive autophagy in podocytes.
AB  - To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high-fat
      diet-induced obesity-related glomerulopathy (ORG). Male C57BL/6 mice fed a high
      fat diet for 12 wk were treated with GLP-1 (200 MUg/kg) or 0.9% saline for 4 wk.
      Fasting blood glucose and insulin and the expression of podocin, nephrin,
      phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and
      microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed. Glomerular
      morphology and podocyte foot structure were evaluated by periodic acid-Schiff
      staining and electron microscopy. Podocytes were treated with 150 nM GLP-1 and
      incubated with 400 MUM palmitic acid (PA) for 12 h. The effect on autophagy was
      assessed by podocyte-specific Glut4 siRNA. Insulin resistance and autophagy were
      assayed by immunofluorescence and Western blotting. The high-fat diet resulted in
      weight gain, ectopic glomerular lipid accumulation, increased insulin resistance,
      and fusion of podophyte foot processes. The decreased translocation of Glut4 to
      the plasma membrane and excess autophagy seen in mice fed a high-fat diet and in
      PA-treated cultured podocytes were attenuated by GLP-1. Podocyte-specific Glut4
      siRNA promoted autophagy, and rapamycin-enhanced autophagy worsened the podocyte
      injury caused by PA. Excess autophagy in podocytes was induced by inhibition of
      Glut4 translocation to the plasma membrane and was involved in the pathology of
      ORG. GLP-1 restored insulin sensitivity and ameliorated renal injury by
      decreasing the level of autophagy.

PMID- 29070573
TI  - miR-34c-5p and CaMKII are involved in aldosterone-induced fibrosis in kidney
      collecting duct cells.
AB  - Mineralocorticoids trigger a profibrotic process in the kidney. In mouse cortical
      collecting duct cells, the present study addressed two main questions: 1) what
      are microRNAs (miRNAs) and their target genes that are changed by aldosterone?
      and 2) what do miRNAs, in response to aldosterone, regulate regarding signaling
      pathways related to fibrosis? A microarray chip assay was done in cells in the
      absence or presence of aldosterone treatment (10-6 M; 3 days). The candidate
      miRNAs were identified by the criteria of >30% of fold change among the
      significantly changed miRNAs ( P < 0.05). Twenty-nine miRNAs were upregulated
      (>1.3-fold), and 27 miRNAs were downregulated (<0.7-fold). Putative target genes
      of identified miRNAs were associated with 74 Kyoto Encyclopedia of Genes and
      Genomes pathways. Among them, the wingless-related integration site (Wnt)
      signaling pathway was highly ranked, where 15 mature miRNAs were observed. These
      miRNAs were further analyzed by real-time quantitative PCR, and among them, miR
      130b-3p, miR-34c-5p, and miR-146a-5p were selected. Through the identification of
      putative target genes of these three miRNAs, mRNA and protein expression of the
      Ca2+/calmodulin-dependent protein kinase type II beta-chain ( Camk2b) gene (a
      target gene of miR-34c-5p) were found to be increased significantly in
      aldosterone-treated cells, where fibronectin (FN) and alpha-smooth muscle actin
      were induced. When CaMKIIbeta small interfering RNA or the miR-34c-5p mimic was
      transfected, aldosterone-induced FN expression was significantly attenuated,
      along with reduced CaMKIIbeta protein expression. A luciferase reporter assay
      revealed a decrease of CaMKIIbeta translation in cells transfected with miRNA
      mimics of miR-34c-5p. In conclusion, aldosterone-induced downregulation of miR
      34c-5p in the Wnt signaling pathway and a consequent increase of CaMKIIbeta
      expression are likely to be involved in aldosterone-induced fibrosis.

PMID- 29070576
TI  - The first artificial pacemaker: the best thing since sliced bread?

PMID- 29070575
TI  - Saphenous nerve stimulation normalizes bladder underactivity induced by tibial
      nerve stimulation in cats.
AB  - This study in alpha-chloralose-anesthetized cats aimed at investigating the
      bladder responses to saphenous nerve stimulation (SNS). A urethral catheter was
      used to infuse the bladder with saline and to record changes in bladder pressure.
      With the bladder fully distended, SNS at 1-Hz frequency and an intensity slightly
      below the threshold (T) for inducing an observable motor response of the hindlimb
      muscles induced large amplitude (40-150 cmH2O) bladder contractions. Application
      of SNS (1 Hz, 2-4T) during cystometrograms (CMGs), when the bladder was slowly (1
      3 ml/min) infused with saline, significantly ( P < 0.05) increased the duration
      of the micturition contraction to >200% of the control without changing bladder
      capacity or contraction amplitude. Repeated application (1-8 times) of intense (4
      8T intensity) 30-min tibial nerve stimulation (TNS) produced prolonged post-TNS
      inhibition that significantly ( P < 0.01) increased bladder capacity to 135.9 +/-
      7.6% and decreased the contraction amplitude to 44.1 +/- 16.5% of the pre-TNS
      control level. During the period of post-TNS inhibition, SNS (1 Hz, 2-4T) applied
      during CMGs completely restored the bladder capacity and the contraction
      amplitude to the pre-TNS control level and almost doubled the duration of the
      micturition contraction. These results indicate that SNS at 1 Hz can facilitate
      the normal micturition reflex and normalize the reflex when it is suppressed
      during post-TNS inhibition. This study provides an opportunity to develop a novel
      neuromodulation therapy for underactive bladder using SNS.

PMID- 29070574
TI  - Cell adhesion molecule-1 shedding induces apoptosis of renal epithelial cells and
      exacerbates human nephropathies.
AB  - Chronic kidney disease (CKD) is an important problem throughout the world,
      associated with the increase of blood urea nitrogen (BUN) and serum creatinine
      (sCre) and with renal tubular injuries. It is crucial to elucidate the molecular
      mechanisms of renal injuries to identify the new therapeutics and early
      diagnostic methods. We focused on cell adhesion molecule-1 (CADM1) protein.
      CADM1, its isoform SP4, is expressed in the epithelial cells of various tissues,
      including renal distal tubules, localized on the lateral cell membrane, mediates
      cell-cell adhesion via trans-homophilic binding, and interacts with various
      proteins. We previously reported that its expression was downregulated by post
      proteolytic cleavage (alpha- and beta-shedding) in pulmonary diseases. To
      investigate whether CADM1 alpha-shedding occurs in human nephropathies, we
      performed Western blotting and immunohistochemical analysis of specimens with
      arterionephrosclerosis (AS) and diabetic nephropathy (DN) from autopsied kidneys.
      CADM1 alpha-shedding was induced in AS and DN kidneys and derived from the
      decrease in full-length CADM1 (FL-CADM1) and increase of the COOH-terminal
      fragment (alpha-CTF). In particular, the reduced FL-CADM1 level was correlated
      with tubular and tubulointerstitial injuries and the increases in BUN and sCre
      levels. Apoptosis of renal tubular epithelial cells (TECs) was promoted in both
      nephropathies, and it was significantly correlated with the decrease in the FL
      CADM1. Furthermore, FL-CADM1 knockdown by small interfering RNA downregulated
      anti-apoptotic Bcl-2 protein and promoted apoptosis of cultured renal TECs. The
      present study suggests that the reduction of FL-CADM1 leads to renal TEC
      apoptosis and could exacerbate renal tubular and tubulointerstitial injuries,
      which contribute to the development of CKD.

PMID- 29070577
TI  - Improving the Clinical Value and Utility of CGM Systems: Issues and
      Recommendations: A Joint Statement of the European Association for the Study of
      Diabetes and the American Diabetes Association Diabetes Technology Working Group.
AB  - The first systems for continuous glucose monitoring (CGM) became available over
      15 years ago. Many then believed CGM would revolutionize the use of intensive
      insulin therapy in diabetes; however, progress toward that vision has been
      gradual. Although increasing, the proportion of individuals using CGM rather than
      conventional systems for self-monitoring of blood glucose on a daily basis is
      still low in most parts of the world. Barriers to uptake include cost,
      measurement reliability (particularly with earlier-generation systems), human
      factors issues, lack of a standardized format for displaying results, and
      uncertainty on how best to use CGM data to make therapeutic decisions. This
      Scientific Statement makes recommendations for systemic improvements in clinical
      use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is
      to improve safety and efficacy in order to support the advancement of the
      technology in achieving its potential to improve quality of life and health
      outcomes for more people with diabetes.

PMID- 29070578
TI  - Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell
      lung carcinoma?
AB  - Chronic obstructive pulmonary disease (COPD) patients are at increased risk of
      developing nonsmall cell lung carcinoma, irrespective of their smoking history.
      Although the mechanisms behind this observation are not clear, established
      drivers of carcinogenesis in COPD include oxidative stress and sustained chronic
      inflammation. Mitochondria are critical in these two processes and recent
      evidence links increased oxidative stress in COPD patients to mitochondrial
      damage. We therefore postulate that mitochondrial damage in COPD patients leads
      to increased oxidative stress and chronic inflammation, thereby increasing the
      risk of carcinogenesis.The functional state of the mitochondrion is dependent on
      the balance between its biogenesis and degradation (mitophagy). Dysfunctional
      mitochondria are a source of oxidative stress and inflammasome activation. In
      COPD, there is impaired translocation of the ubiquitin-related degradation
      molecule Parkin following activation of the Pink1 mitophagy pathway, resulting in
      excessive dysfunctional mitochondria. We hypothesise that deranged pathways in
      mitochondrial biogenesis and mitophagy in COPD can account for the increased risk
      in carcinogenesis. To test this hypothesis, animal models exposed to cigarette
      smoke and developing emphysema and lung cancer should be developed. In the
      future, the use of mitochondria-based antioxidants should be studied as an
      adjunct with the aim of reducing the risk of COPD-associated cancer.

PMID- 29070579
TI  - Use of multitarget tyrosine kinase inhibitors to attenuate platelet-derived
      growth factor signalling in lung disease.
AB  - Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) play a
      fundamental role in the embryonic development of the lung. Aberrant PDGF
      signalling has been documented convincingly in a large variety of pulmonary
      diseases, including idiopathic pulmonary arterial hypertension, lung cancer and
      lung fibrosis. Targeting PDGF signalling has been proven to be effective in these
      diseases. In clinical practice, the most effective way to block PDGF signalling
      is to inhibit the activity of the intracellular PDGFR kinases. Although the
      mechanism of action of such drugs is not specific for PDGF signalling, the
      medications have a broad therapeutic index that allows clinical use. The safety
      profile and therapeutic opportunities of these and future medications that target
      PDGFs and PDGFRs are reviewed.

PMID- 29070580
TI  - COPD in individuals with the PiMZ alpha-1 antitrypsin genotype.
AB  - Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk
      factor for emphysema, there has been ongoing debate over whether individuals with
      intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at
      some risk for emphysema. This is important, because MZ individuals comprise 2-5%
      of the general population. In this review we summarise the evidence about the
      risks of the MZ population to develop emphysema or asthma. We discuss the
      different study designs that have tried to answer this question. The risk of
      emphysema is more pronounced in case-control than in population-based studies,
      perhaps due to inadequate power. Carefully designed family studies show an
      increased risk of emphysema in MZ smokers. This is supported by the rapid decline
      in lung function of MZ individuals when compared to the general population after
      massive environmental exposures. The risk of asthma in MZ subjects is less
      studied, and more literature is needed before firm conclusions can be made.
      Augmentation therapy in MZ individuals is not supported by any objective studies.
      MZ smokers are at increased risk for emphysema that is more pronounced when other
      environmental challenges are present.

PMID- 29070581
TI  - Personalised medicine in sleep respiratory disorders: focus on obstructive sleep
      apnoea diagnosis and treatment.
AB  - In all fields of medicine, major efforts are currently dedicated to improve the
      clinical, physiological and therapeutic understanding of disease, and obstructive
      sleep apnoea (OSA) is no exception. The personalised medicine approach is
      relevant for OSA, given its complex pathophysiology and variable clinical
      presentation, the interactions with comorbid conditions and its possible
      contribution to poor outcomes. Treatment with continuous positive airway pressure
      (CPAP) is effective, but CPAP is poorly tolerated or not accepted in a
      considerable proportion of OSA patients. This review summarises the available
      studies on the physiological phenotypes of upper airway response to obstruction
      during sleep, and the clinical presentations of OSA (phenotypes and clusters)
      with a special focus on our changing attitudes towards approaches to treatment.
      Such major efforts are likely to change and expand treatment options for OSA
      beyond the most common current choices (i.e CPAP, mandibular advancement devices,
      positional treatment, lifestyle changes or upper airway surgery). More
      importantly, treatment for OSA may become more effective, being tailored to each
      patient's need.

PMID- 29070583
TI  - "Intersections of lung progenitor cells, lung disease and lung cancer." Carla F.
      Kim. Eur Respir Rev 2017; 26: 170054.

PMID- 29070582
TI  - Lung segmentectomy: does it offer a real functional benefit over lobectomy?
AB  - Anatomical segmentectomy has been developed to offer better pulmonary function
      preservation than lobectomy, in stage IA lung cancer. Despite the retrospective
      nature of most of the studies and the lack of randomised studies, a substantial
      body of literature today allows us to evaluate to what extent lung function
      decreases after segmentectomy and whether segmentectomy offers a real functional
      benefit over lobectomy. From the available series, it emerges that the mean
      decrease in forced expiratory volume in 1 s (FEV1) is low, ranging from -9% to 
      24% of the initial value within 2 months and -3 to -13% 12 months after
      segmentectomy. This reduction in lung function is significantly lower than that
      induced by lobectomy, but saves only a few per cent of pre-operative FEV1
      Moreover, the published results do not firmly establish the functional benefit of
      segmentectomy over lobectomy in patients with poor lung function. Some issues
      remain to be addressed, including whether video-assisted thoracic surgery (VATS)
      segmentectomy may preserve lung function better than VATS lobectomy in patients
      with poor lung function, especially within the early days after surgery, and
      whether this may translate to lowering the functional limit for surgery.
      Eventually, trials comparing stereotactic ablative body radiotherapy,
      radiofrequency ablation and segmentectomy functional consequences are warranted.

PMID- 29070584
TI  - MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier
      permeability by targeting Homeobox A5.
AB  - Blood-brain barrier (BBB) disruption plays a critical role in brain injury
      induced by cerebral ischemia, and preserving BBB integrity during ischemia could
      alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB
      disruption by using models of rat middle cerebral artery occlusion and cell
      oxygen-glucose deprivation. We found that ischemia significantly increased
      microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain
      microvascular endothelial cells. Antagomir-130a, an antagonist of miR-130a, could
      attenuate brain edema, lower BBB permeability, reduce infarct volume, and improve
      neurologic function. MiR-130a overexpression induced by miR-130a mimic increased
      monolayer permeability, and intercellular inhibition of miR-130a by a miR-130a
      inhibitor suppressed oxygen-glucose deprivation-induced increase in monolayer
      permeability. Moreover, dual luciferase reporter system showed that Homeobox A5
      was the direct target of miR-130a. MiR-130a, by inhibiting Homeobox A5
      expression, could down-regulate occludin, thereby increasing BBB permeability.
      Our results suggested that miR-130a might be implicated in ischemia-induced BBB
      dysfunction and serve as a target for the treatment of ischemic stroke.-Wang, Y.,
      Wang, M.-D., Xia, Y.-P., Gao, Y., Zhu, Y.-Y., Chen, S.-C., Mao, L., He, Q.-W.,
      Yue, Z.-Y., Hu, B. MicroRNA-130a regulates cerebral ischemia-induced blood-brain
      barrier permeability by targeting Homeobox A5.

PMID- 29070586
TI  - FAK controls the mechanical activation of YAP, a transcriptional regulator
      required for durotaxis.
AB  - Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates
      fundamental processes in cells such as growth, survival, and migration. FAK is
      one of the first molecules recruited to focal adhesions in response to external
      mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling,
      and relays these stimuli to other mechanotransducers within the cytoplasm. Yes
      associated protein (YAP) has been identified recently as one of these core
      mechanotransducers. YAP translocates to the nucleus following changes in cell
      mechanics to promote the expression of genes implicated in motility, apoptosis,
      proliferation, and organ growth. Here, we show that FAK controls the nuclear
      translocation and activation of YAP in response to mechanical activation and
      submit that the YAP-dependent process of durotaxis requires a cell with an
      asymmetric distribution of active and inactive FAK molecules.-Lachowski, D.,
      Cortes, E., Robinson, B., Rice, A., Rombouts, K., Del Rio Hernandez, A. E. FAK
      controls the mechanical activation of YAP, a transcriptional regulator required
      for durotaxis.

PMID- 29070585
TI  - NLRC5 deficiency ameliorates diabetic nephropathy through alleviating
      inflammation.
AB  - NOD-like receptor family caspase recruitment domain family domain containing 5
      (NLRC5) has important roles in inflammation and innate immunity. NLRC5 was highly
      expressed in kidney from streptozotocin-induced diabetic mice, db/ db mice and
      patients with diabetes. Based on that evidence, the present study was designed to
      explore the roles of NLRC5 in the progression of diabetic nephropathy (DN). We
      examined kidney injury, including inflammation and fibrosis in Nlrc5 gene
      knockout ( Nlrc5-/-) and wild-type (WT) diabetic mice. We found that Nlrc5-/-
      mice developed less-severe diabetic kidney injury compared with WT mice,
      exhibiting lower albuminuria, less fibronectin and collagen IV expression, and
      reduced macrophage infiltration but greater levels of podocin and nephrin in the
      diabetic kidney. The underlying mechanisms were further investigated in vitro
      with peritoneal macrophages and mesangial cells treated with high glucose.
      Reduced proinflammatory effect was observed in peritoneal macrophages from Nlrc5
      /- mice, associated with NF-kappaB pathway suppression. Knocking down of NLRC5 in
      mesangial cells in high-glucose conditions was also associated with reduced NF
      kappaB and TGF-beta/Smad signaling. Taken together, NLRC5 promotes inflammation
      and fibrosis during DN progression partly through the effects on NF-kappaB and
      TGF-beta/Smad pathways. NLRC5 may, therefore, be a promising therapeutic target
      for DN treatment.-Luan, P., Zhuang, J., Zou, J., Li, H., Shuai, P., Xu, X., Zhao,
      Y., Kou, W., Ji, S., Peng, A., Xu, Y., Su, Q., Jian, W., Peng, W. NLRC5
      deficiency ameliorates diabetic nephropathy through alleviating inflammation.

PMID- 29070588
TI  - Do extra-group fertilizations increase the potential for sexual selection in male
      mammals?
AB  - Fertilizations by males outside the social breeding group (extra-group paternity,
      EGP) are widespread in birds and mammals. EGP is generally proposed to increase
      male reproductive skew and thereby increase the potential for sexual selection,
      but the generality of this relationship is unclear. We extracted data from 27
      mammals in seven orders and used phylogenetic comparative methods to investigate
      the influence of EGP and social mating system on measures of inequality in male
      fertilization success, which are indices of the potential for sexual selection.
      We find that EGP and social mating system can predict the potential for sexual
      selection in mammalian populations, but only when considered jointly and not
      individually. EGP appears to increase the potential for sexual selection but only
      when the degree of social polygyny is relatively low. When social polygyny is
      high, EGP appears to result in a more uniform distribution of reproduction and a
      decrease in the potential for sexual selection. A possible explanation to be
      investigated is that the phenotype of extra-group fathers differs systematically
      across social mating systems. Our findings have implications for the use of EGP
      and social mating system as indices of sexual selection in comparative analyses
      of trait evolution under sexual selection.

PMID- 29070587
TI  - Ghrelin protects against osteoarthritis through interplay with Akt and NF-kappaB
      signaling pathways.
AB  - Osteoarthritis (OA) is a common chronic degenerative disease characterized by
      degeneration in the joints and subsequent destruction of cartilage and bone, yet
      much remains to be elucidated regarding its molecular mechanism. Ghrelin is a
      recently discovered neuropeptide with anti-inflammatory actions, but it is
      unknown whether ghrelin is involved in OA. Human primary chondrocyte and
      cartilage samples were collected from patients with OA, and the expression
      pattern of ghrelin was assessed. Human chondrocyte and cartilage samples were
      stimulated with IL-1beta and TNF-alpha, and exogenous ghrelin-alleviated
      disorganization of catabolism and anabolism were mediated by IL-1beta and TNF
      alpha. Destabilization of the medial meniscus and anterior cruciate ligament
      transection models were established in wild-type mice that were administered
      ghrelin or PBS. Severity of inflammation and degeneration in the joints were
      determined by measuring the levels of various inflammatory cytokines and
      degeneration-associated molecules. Ghrelin down-regulated the production of
      various inflammatory cytokines, inhibited apoptosis of chondrocytes, decreased
      the levels of metalloproteinases (including matrix metalloproteinase-13 and a
      disintegrin and metalloproteinase with thrombospondin motif-5), and maintained
      the expression of critical matrix components, such as aggrecan and collagen 2.
      Moreover, suppression of the Akt signaling pathway and activation of NF-kappaB
      signaling in chondrocytes during OA development was antagonized by ghrelin
      administration. This supports the assessment of ghrelin as a potential
      therapeutic approach to treat degenerative cartilage diseases, including OA.-Qu,
      R., Chen, X., Wang, W., Qiu, C., Ban, M., Guo, L., Vasilev, K., Chen, J., Li, W.,
      Zhao, Y. Ghrelin protects against osteoarthritis through interplay with Akt and
      NF-kappaB signaling pathways.

PMID- 29070589
TI  - Mitochondria-targeted molecules determine the redness of the zebra finch bill.
AB  - The evolution and production mechanisms of red carotenoid-based ornaments in
      animals are poorly understood. Recently, it has been suggested that enzymes
      transforming yellow carotenoids to red pigments (ketolases) in animal cells may
      be positioned in the inner mitochondrial membrane (IMM) intimately linked to the
      electron transport chain. These enzymes may mostly synthesize coenzyme Q10
      (coQ10), a key redox-cycler antioxidant molecularly similar to yellow
      carotenoids. It has been hypothesized that this shared pathway favours the
      evolution of red traits as sexually selected individual quality indices by
      revealing a well-adjusted oxidative metabolism. We administered mitochondria
      targeted molecules to male zebra finches (Taeniopygia guttata) measuring their
      bill redness, a trait produced by transforming yellow carotenoids. One molecule
      included coQ10 (mitoquinone mesylate, MitoQ) and the other one (decyl
      triphenylphosphonium; dTPP) has the same structure without the coQ10 aromatic
      ring. At the highest dose, the bill colour of MitoQ and dTPP birds strongly
      differed: MitoQ birds' bills were redder and dTPP birds showed paler bills even
      compared to birds injected with saline only. These results suggest that ketolases
      are indeed placed at the IMM and that coQ10 antioxidant properties may improve
      their efficiency. The implications for evolutionary theories of sexual signalling
      are discussed.

PMID- 29070590
TI  - Modelling the effects of short and random proto-neural elongations.
AB  - To understand how neurons and nervous systems first evolved, we need an account
      of the origins of neural elongations: why did neural elongations (axons and
      dendrites) first originate, such that they could become the central component of
      both neurons and nervous systems? Two contrasting conceptual accounts provide
      different answers to this question. Braitenberg's vehicles provide the iconic
      illustration of the dominant input-output (IO) view. Here, the basic role of
      neural elongations is to connect sensors to effectors, both situated at different
      positions within the body. For this function, neural elongations are thought of
      as comparatively long and specific connections, which require an articulated body
      involving substantial developmental processes to build. Internal coordination
      (IC) models stress a different function for early nervous systems. Here, the
      coordination of activity across extended parts of a multicellular body is held
      central, in particular, for the contractions of (muscle) tissue. An IC
      perspective allows the hypothesis that the earliest proto-neural elongations
      could have been functional even when they were initially simple, short and random
      connections, as long as they enhanced the patterning of contractile activity
      across a multicellular surface. The present computational study provides a proof
      of concept that such short and random neural elongations can play this role.
      While an excitable epithelium can generate basic forms of patterning for small
      body configurations, adding elongations allows such patterning to scale up to
      larger bodies. This result supports a new, more gradual evolutionary route
      towards the origins of the very first neurons and nervous systems.

PMID- 29070591
TI  - Anchoring like octopus: biologically inspired soft artificial sucker.
AB  - This paper presents a robotic anchoring module, a sensorized mechanism for
      attachment to the environment that can be integrated into robots to enable or
      enhance various functions such as robot mobility, remaining on location or its
      ability to manipulate objects. The body of the anchoring module consists of two
      portions with a mechanical stiffness transition from hard to soft. The hard
      portion is capable of containing vacuum pressure used for actuation while the
      soft portion is highly conformable to create a seal to contact surfaces. The
      module is integrated with a single sensory unit which exploits a fibre-optic
      sensing principle to seamlessly measure proximity and tactile information for use
      in robot motion planning as well as measuring the state of firmness of its
      anchor. In an experiment, a variable set of physical loads representing the
      weights of potential robot bodies were attached to the module and its ability to
      maintain the anchor was quantified under constant and variable vacuum pressure
      signals. The experiment shows the effectiveness of the module in quantifying the
      state of firmness of the anchor and discriminating between different amounts of
      physical loads attached to it. The proposed anchoring module can enable many
      industrial and medical applications where attachment to environment is of crucial
      importance for robot control.

PMID- 29070595
TI  - Just four UK postgraduate surgical training posts meet national quality
      standards, study finds.

PMID- 29070592
TI  - Enamel crystallite strength and wear: nanoscale responses of teeth to chewing
      loads.
AB  - The nanoscale responses of teeth to chewing loads are poorly understood. This has
      contributed to debate concerning the aetiology of enamel wear and resistance to
      fracture. Here we develop a new model for reactions of individual hydroxyapatite
      nanofibres to varying loads and directions of force. Hydroxyapatite nanofibres,
      or crystallites, composed of chains of bonded nanospheres, are the fundamental
      building blocks of enamel. This study indicates that these nanofibres respond to
      contact pressure in three distinct ways depending on force magnitude and
      direction: (i) plucking (nanosphere loss when the strength of the bonding protein
      'glue' is exceeded), (ii) plastic deformation (compression to gradually bend
      nanofibres and squeeze the protein layer), and (iii) fragmentation (nanofibres
      fracture when the strength of H-bonds that bind smaller nanoparticles into
      nanospheres is exceeded). Critical contact pressure to initiate plucking is the
      lowest, followed by plastic deformation, and then fragmentation. Further, lower
      contact pressures are required for a response with shear forces applied
      perpendicular to the long axes of crystallites than with crushing forces parallel
      to them alone. These nanoscale responses are explained as a function of the
      interfacial nanochemical bonding between and within individual crystallites. In
      other words, nanochemistry plays a critical role in the responses of enamel to
      varying chewing loads.

PMID- 29070593
TI  - Body lift, drag and power are relatively higher in large-eared than in small
      eared bat species.
AB  - Bats navigate the dark using echolocation. Echolocation is enhanced by external
      ears, but external ears increase the projected frontal area and reduce the
      streamlining of the animal. External ears are thus expected to compromise flight
      efficiency, but research suggests that very large ears may mitigate the cost by
      producing aerodynamic lift. Here we compare quantitative aerodynamic measures of
      flight efficiency of two bat species, one large-eared (Plecotus auritus) and one
      small-eared (Glossophaga soricina), flying freely in a wind tunnel. We find that
      the body drag of both species is higher than previously assumed and that the
      large-eared species has a higher body drag coefficient, but also produces
      relatively more ear/body lift than the small-eared species, in line with prior
      studies on model bats. The measured aerodynamic power of P. auritus was higher
      than predicted from the aerodynamic model, while the small-eared species aligned
      with predictions. The relatively higher power of the large-eared species results
      in lower optimal flight speeds and our findings support the notion of a trade-off
      between the acoustic benefits of large external ears and aerodynamic performance.
      The result of this trade-off would be the eco-morphological correlation in bat
      flight, with large-eared bats generally adopting slow-flight feeding strategies.

PMID- 29070596
TI  - Five minutes with . . . Allan Colver.

PMID- 29070594
TI  - A smoke-free world to protect child health.

PMID- 29070597
TI  - Three forms of identification and a letter from God.

PMID- 29070598
TI  - Should we scrap the target of a maximum four hour wait in emergency departments?

PMID- 29070599
TI  - BMJ declares its revenues from industry.

PMID- 29070600
TI  - Sixty seconds on . . . bioelectronics.

PMID- 29070602
TI  - Junior doctor-should the term be abandoned?

PMID- 29070601
TI  - Research integrity has become complacent and lacks transparency, MPs hear.

PMID- 29070604
TI  - Khalid Khan: Cricketer in chief.

PMID- 29070603
TI  - Let patients be custodians of their own medical records.

PMID- 29070605
TI  - Lessons in planning from mass casualty events in UK.

PMID- 29070606
TI  - Treatment of hemorrhagic head and neck lesions by direct puncture and nBCA
      embolization.
AB  - Life-threatening bleeding in the head and neck region requires urgent management.
      These hemorrhagic lesions, for example, a ruptured pseudoaneurysm, are often
      treated by transarterial embolization (TAE), but prior intervention or surgery,
      inflammation, anatomic variants, and vessel tortuosity may render an endovascular
      approach challenging, time-consuming, and sometimes impossible. We report two
      cases of severe head and neck hemorrhages successfully embolized with n-butyl
      cyanoacrylate via direct puncture, and propose this approach as a fast, safe, and
      effective alternative to TAE.

PMID- 29070607
TI  - Contribution of de novo and mosaic TP53 mutations to Li-Fraumeni syndrome.
AB  - BACKGROUND: Development of tumours such as adrenocortical carcinomas (ACC),
      choroid plexus tumours (CPT) or female breast cancers before age 31 or multiple
      primary cancers belonging to the Li-Fraumeni (LFS) spectrum is, independently of
      the familial history, highly suggestive of a germline TP53 mutation. The aim of
      this study was to determine the contribution of de novo and mosaic mutations to
      LFS. METHODS AND RESULTS: Among 328 unrelated patients harbouring a germline TP53
      mutation identified by Sanger sequencing and/or QMPSF, we could show that the
      mutations had occurred de novo in 40 cases, without detectable parental age
      effect. Sanger sequencing revealed two mosaic mutations in a child with ACC and
      in an unaffected father of a child with medulloblastoma. Re-analysis of blood DNA
      by next-generation sequencing, performed at a depth above 500X, from 108 patients
      suggestive of LFS without detectable TP53 mutations, allowed us to identify 6
      additional cases of mosaic TP53 mutations, in 2/49 children with ACC, 2/21
      children with CPT, in 1/31 women with breast cancer before age 31 and in a
      patient who developed an osteosarcoma at age 12, a breast carcinoma and a breast
      sarcoma at age 35. CONCLUSIONS: This study performed on a large series of TP53
      mutation carriers allows estimating the contribution to LFS of de novo mutations
      to at least 14% (48/336) and suggests that approximately one-fifth of these de
      novo mutations occur during embryonic development. Considering the medical impact
      of TP53 mutation identification, medical laboratories in charge of TP53 testing
      should ensure the detection of mosaic mutations.

PMID- 29070608
TI  - Stem cells: Aging and transcriptional fingerprints.
AB  - Stem cells are imbued with unique qualities. They have the capacity to propagate
      themselves through symmetric divisions and to divide asymmetrically to engender
      new cells that can progress to differentiate into tissue-specific, terminal cell
      types. Armed with these qualities, stem cells in adult tissues are tasked with
      replacing decaying cells and regenerating tissue after injury to maintain optimal
      tissue function. With increasing age, stem cell functional abilities decline,
      resulting in reduced organ function and delays in tissue repair. Here, we review
      the effect of aging in five well-studied adult murine stem cell populations and
      explore age-related declines in stem cell function and their consequences for
      stem cell self-renewal, tissue homeostasis, and regeneration. Finally, we examine
      transcriptional changes that have been documented in aged stem cell populations
      and discuss new questions and future directions that this collection of data has
      uncovered.

PMID- 29070610
TI  - Mitochondrial determinants of mammalian longevity.
AB  - Current ageing theories are far from satisfactory because of the many
      determinants involved in ageing. The well-known rate-of-living theory assumes
      that the product (lifetime energy expenditure, LEE) of maximum lifespan (MLS) and
      mass-specific basal metabolic rate (msBMR) is approximately constant. Although
      this theory provides a significant inverse correlation between msBMR and MLS as a
      whole for mammals, it remains problematic for two reasons. First, several
      interspecies studies within respective orders (typically within rodents) have
      shown no inverse relationships between msBMR and MLS. Second, LEE values widely
      vary in mammals and birds. Here, to solve these two problems, we introduced a new
      quantity designated as mitochondrial (mt) lifetime energy output, mtLEO = MLS *
      mtMR, in place of LEE, by using the mt metabolic rate (mtMR) per mitochondrion.
      Thereby, we found that mtLEO values were distributed more narrowly than LEE ones,
      and strongly correlated with the four amino-acid variables (AAVs) of Ser, Thr and
      Cys contents and hydrophobicity of mtDNA-encoded membrane proteins (these
      variables were related to the stability of these proteins). Consequently, only
      these two mt items, mtMR and the AAVs, solved the above-mentioned problems in the
      rate-of-living theory, and thus extensively improved the correlation with MLS
      compared with that given by LEE.

PMID- 29070609
TI  - The parasite Toxoplasma sequesters diverse Rab host vesicles within an
      intravacuolar network.
AB  - Many intracellular pathogens subvert host membrane trafficking pathways to
      promote their replication. Toxoplasma multiplies in a membrane-bound
      parasitophorous vacuole (PV) that interacts with mammalian host organelles and
      intercepts Golgi Rab vesicles to acquire sphingolipids. The mechanisms of host
      vesicle internalization and processing within the PV remain undefined. We
      demonstrate that Toxoplasma sequesters a broad range of Rab vesicles into the PV.
      Correlative light and electron microscopy analysis of infected cells illustrates
      that intravacuolar Rab1A vesicles are surrounded by the PV membrane, suggesting a
      phagocytic-like process for vesicle engulfment. Rab11A vesicles concentrate to an
      intravacuolar network (IVN), but this is reduced in Deltagra2 and
      Deltagra2Deltagra6 parasites, suggesting that tubules stabilized by the TgGRA2
      and TgGRA6 proteins secreted by the parasite within the PV contribute to host
      vesicle sequestration. Overexpression of a phospholipase TgLCAT, which is
      localized to the IVN, results in a decrease in the number of intravacuolar GFP
      Rab11A vesicles, suggesting that TgLCAT controls lipolytic degradation of Rab
      vesicles for cargo release.

PMID- 29070613
TI  - Copanlisib Produces Prolonged Responses in Lymphoma.
AB  - A phase II trial of the pan-class I PI3K inhibitor copanlisib demonstrated that
      it induces objective responses in 59% of patients with relapsed or refractory
      indolent lymphoma. The responses lasted a median of 22.6 months. Although the
      drugs weren't compared head to head, researchers suspect that the side effects of
      copanlisib may be less severe than those of idelalisib, another PI3K inhibitor.

PMID- 29070611
TI  - Solution structure of CXCL13 and heparan sulfate binding show that GAG binding
      site and cellular signalling rely on distinct domains.
AB  - Chemokines promote directional cell migration through binding to G-protein
      coupled receptors, and as such are involved in a large array of developmental,
      homeostatic and pathological processes. They also interact with heparan sulfate
      (HS), the functional consequences of which depend on the respective location of
      the receptor- and the HS-binding sites, a detail that remains elusive for most
      chemokines. Here, to set up a biochemical framework to investigate how HS can
      regulate CXCL13 activity, we solved the solution structure of CXCL13. We showed
      that it comprises an unusually long and disordered C-terminal domain, appended to
      a classical chemokine-like structure. Using three independent experimental
      approaches, we found that it displays a unique association mode to HS, involving
      two clusters located in the alpha-helix and the C-terminal domain. Computational
      approaches were used to analyse the HS sequences preferentially recognized by the
      protein and gain atomic-level understanding of the CXCL13 dimerization induced
      upon HS binding. Starting with four sets of 254 HS tetrasaccharides, we
      identified 25 sequences that bind to CXCL13 monomer, among which a single one
      bound to CXCL13 dimer with high consistency. Importantly, we found that CXCL13
      can be functionally presented to its receptor in a HS-bound form, suggesting that
      it can promote adhesion-dependent cell migration. Consistently, we designed
      CXCL13 mutations that preclude interaction with HS without affecting CXCR5
      dependent cell signalling, opening the possibility to unambiguously demonstrate
      the role of HS in the biological function of this chemokine.

PMID- 29070612
TI  - Predicting virus emergence amid evolutionary noise.
AB  - The study of virus disease emergence, whether it can be predicted and how it
      might be prevented, has become a major research topic in biomedicine. Here we
      show that efforts to predict disease emergence commonly conflate fundamentally
      different evolutionary and epidemiological time scales, and are likely to fail
      because of the enormous number of unsampled viruses that could conceivably emerge
      in humans. Although we know much about the patterns and processes of virus
      evolution on evolutionary time scales as depicted in family-scale phylogenetic
      trees, these data have little predictive power to reveal the short-term
      microevolutionary processes that underpin cross-species transmission and
      emergence. Truly understanding disease emergence therefore requires a new
      mechanistic and integrated view of the factors that allow or prevent viruses
      spreading in novel hosts. We present such a view, suggesting that both ecological
      and genetic aspects of virus emergence can be placed within a simple population
      genetic framework, which in turn highlights the importance of host population
      size and density in determining whether emergence will be successful. Despite
      this framework, we conclude that a more practical solution to preventing and
      containing the successful emergence of new diseases entails ongoing virological
      surveillance at the human-animal interface and regions of ecological disturbance.

PMID- 29070614
TI  - Type I IFN Receptor Signaling Controls IL7-Dependent Accumulation and Activity of
      Protumoral IL17A-Producing gammadeltaT Cells in Breast Cancer.
AB  - The protumoral activity of gammadeltaT17 cells has recently emerged in a wide
      variety of solid malignancies, including breast cancer. These cells exert their
      detrimental functions by promoting tumor growth, angiogenesis, and subsequent
      metastasis development. However, the intratumoral factors that regulate the
      biology of gammadeltaT17cells within the tumor microenvironment are less well
      understood. Here, using two experimental models of breast cancer, we reinforced
      the concept that tumor-infiltrating gammadeltaT17 cells are endowed with
      protumoral functions, which promote tumor progression and metastasis development.
      More importantly, we demonstrated a critical role for type I IFN signaling in
      controlling the preferential accumulation in the tumor bed of a peculiar subset
      of gammadeltaT17 cells displaying a CD27- CD3bright phenotype (previously
      associated with the invariant Vgamma6Vdelta1+ TCR). Interestingly, this effect
      was indirect and partially relied on the IFNAR1-dependent control of IL7
      secretion, a factor that triggers proliferation and activating functions of
      deleterious gammadeltaT17 cells. Our work therefore identifies a key role of the
      type I IFN/IL7 axis in the regulation of intratumoral gammadeltaT17-cell
      functions and in the development of primary breast tumor growth and
      metastasis.Significance: Tumor-derived IL7 can represent a therapeutic target to
      prevent accumulation of immune cells endowed with potent protumoral activities.
      Cancer Res; 78(1); 195-204. (c)2017 AACR.

PMID- 29070617
TI  - Dieulafoy's lesion of the colon and rectum: a case series and literature review.
AB  - Dieulafoy's lesion is a dilated, aberrant, submucosal vessel that erodes the
      overlying epithelium without obvious ulceration. It is most commonly located in
      the lesser curvature of the stomach but rare occurrences in extragastric sites
      have also been reported. Herein, we describe a case series of three patients who
      presented with lower gastrointestinal bleeding. Colonoscopy revealed a caliber
      persistent tortuous submucosal artery protruding into the lumen of the colon or
      rectum. The patients were diagnosed with Dieulafoy's lesion and primary
      haemostasis was achieved with the endoscopic haemoclip application. The purpose
      of this review is to summarise the available data on the pathophysiology,
      epidemiology, clinical presentation, diagnosis and management of patients with
      Dieulafoy's lesion of the colon and rectum.

PMID- 29070615
TI  - Mitochondrial Haplotype Alters Mammary Cancer Tumorigenicity and Metastasis in an
      Oncogenic Driver-Dependent Manner.
AB  - Using a novel mouse model, a mitochondrial-nuclear exchange model termed MNX, we
      tested the hypothesis that inherited mitochondrial haplotypes alter primary tumor
      latency and metastatic efficiency. Male FVB/N-Tg(MMTVneu)202Mul/J (Her2)
      transgenic mice were bred to female MNX mice having FVB/NJ nuclear DNA with
      either FVB/NJ, C57BL/6J, or BALB/cJ mtDNA. Pups receiving the C57BL/6J or BALB/cJ
      mitochondrial genome (i.e., females crossed with Her2 males) showed significantly
      (P < 0.001) longer tumor latency (262 vs. 293 vs. 225 days), fewer pulmonary
      metastases (5 vs. 7 vs. 15), and differences in size of lung metastases (1.2 vs.
      1.4 vs. 1.0 mm diameter) compared with FVB/NJ mtDNA. Although polyoma virus
      middle T-driven tumors showed altered primary and metastatic profiles in previous
      studies, depending upon nuclear and mtDNA haplotype, the magnitude and direction
      of changes were not the same in the HER2-driven mammary carcinomas. Collectively,
      these results establish mitochondrial polymorphisms as quantitative trait loci in
      mammary carcinogenesis, and they implicate distinct interactions between tumor
      drivers and mitochondria as critical modifiers of tumorigenicity and metastasis.
      Cancer Res; 77(24); 6941-9. (c)2017 AACR.

PMID- 29070618
TI  - Successful obstetric and anaesthetic management of a pregnant woman with
      achondroplasia.
AB  - Achondroplasia is the most prevalent form of dwarfism, and there is little
      evidence about the optimal management of pregnant women with achondroplasia. We
      presented a 25-year-old primigravid woman with achondroplasia who was followed up
      during the pregnancy period and performed elective caesarean section with
      combined spinal-epidural anaesthesia at the 38th week of gestation. Frequent
      obstetric follow-up visits and invasive prenatal diagnostic tests should be
      offered during the antenatal period due to the increased risk for obstetric
      complications, such as premature delivery and fetal anomalies. Prenatal detailed
      counselling, comprehensive evaluation of the potential risks, obstetric and
      perioperative management should be performed by a multidisciplinary care team,
      including an obstetrician, anaesthesiologist, pulmonologist, cardiologist and
      neonatologist.

PMID- 29070619
TI  - Circular mapping catheter entrapment in mitral valve apparatus requiring
      emergency surgery: a rarely reported complication of pulmonary vein isolation
      procedure for atrial fibrillation.
AB  - Lasso catheter (Biosense Webster) is one of the most commonly employed circular
      mapping catheters during pulmonary vein isolation (PVI) procedure for atrial
      fibrillation (AF). Although this catheter has greatly facilitated arrhythmia
      mapping, it can be associated with serious complications. We report a case of a
      59-year-old man who underwent PVI procedure for persistent AF. During the
      procedure, the Lasso catheter inadvertently slipped into the left ventricular
      cavity and entangled in the mitral valve apparatus. Various percutaneous
      manoeuvres to release the catheter were unsuccessful and the patient ultimately
      required emergency open heart surgery to remove the catheter and repair the
      valve. To the best of our knowledge, such a case has not previously been reported
      in the UK necessitating an immediate open heart surgery, avoiding replacement of
      the valve.

PMID- 29070616
TI  - Results from the European Prospective Investigation into Cancer and Nutrition
      Link Vitamin B6 Catabolism and Lung Cancer Risk.
AB  - Circulating pyridoxal-5'-phosphate (PLP) has been linked to lung cancer risk. The
      PAr index, defined as the ratio 4-pyridoxic acid/(pyridoxal + PLP), reflects
      increased vitamin B6 catabolism during inflammation. PAr has been defined as a
      marker of lung cancer risk in a prospective cohort study, but analysis of a
      larger numbers of cases are needed to deepen the significance of this study.
      Here, we conducted a nested case-control study within the European Prospective
      Investigation into Cancer and Nutrition (EPIC, n = 521,330), which included 892
      incident lung cancer cases and 1,748 controls matched by center, gender, date of
      blood collection, and date of birth. The association of PAr with risk of lung
      cancer was evaluated by using conditional logistic regression. Study participants
      with elevated PAr experienced higher risk of lung cancer in a dose-response
      fashion, with a doubling in PAr levels associated with 52% higher odds of lung
      cancer after adjustment for tobacco smoking, serum cotinine levels, educational
      attainment, and BMI [OR, 1.52; 95% confidence interval (CI) 1.27-1.81; P <
      0.001]. Additional adjustment for intake of vegetables and fruits and physical
      activity did not materially affect risk association. The association of PAr with
      lung cancer risk was similar in both genders but slightly stronger in former
      smokers and in participants diagnosed with squamous cell carcinoma. This study
      provides robust evidence that increased vitamin B6 catabolism is independently
      associated with a higher risk of future lung cancer.Significance: This large
      cohort study firmly establishes an association between an index of vitamin B6
      levels with lung cancer risk. Cancer Res; 78(1); 302-8. (c)2017 AACR.

PMID- 29070620
TI  - Special variant of histiocytosis.
AB  - Indeterminate cell histiocytosis is a rare variant of histiocytosis. The
      diagnosis is currently based on presence and absence of immunohistochemical
      markers. The current case described an indeterminate cell histiocytosis with ETV3
      NCOA2 translocation.

PMID- 29070621
TI  - Fatal outcome of an anaplastic thyroid tumour.
AB  - Anaplastic thyroid cancer is a rare form of thyroid cancer, known for its very
      poor prognosis, even with the appropriate management. It is very aggressive, with
      a tendency to invade locally and lymph node metastasis is often present at the
      time of diagnosis. We present an elderly patient, who presented with rapid
      enlarging neck mass, which, within weeks, led to his death. His family gave their
      consent to perform an autopsy, and here we describe and illustrate the profound
      aggressiveness of this tumour.

PMID- 29070622
TI  - Sepsis + ptosis = an unusual diagnosis.
AB  - The authors present the case of a 19-year old man presenting to the emergency
      department with a 2-day history of left eye pain and ptosis, facial pain around
      the maxillae, coryza, headaches and fevers. He had a background of autism, mild
      learning disability, obsessive-compulsive disorder and asthma. Within the last
      month, his risperidone and sertraline doses had been increased. Basic
      observations and investigations suggested sepsis: tachypnoea, sinus tachycardia,
      fever and a raised white cell count and C reactive protein level. A CT head
      showed sinonasal polyposis and moderate chronic rhinosinusitis, with normal
      intracranial appearances. An MRI head showed evidence of extension of frontal
      sinus infection through the posterior wall of the left frontal sinus with
      subsequent left frontal extradural empyema. Intravenous antibiotics and surgical
      drainage of the left frontal sinus resulted in clinical improvement and discharge
      to complete the course of antibiotics in the community.

PMID- 29070623
TI  - Large pituitary gland with an expanding lesion in the context of
      neurofibromatosis 1.

PMID- 29070624
TI  - Lithium overdose and delayed severe neurotoxicity: timing for renal replacement
      therapy and restarting of lithium.
AB  - This is a case report of a man in his 60s who presented to an English hospital
      following a significant lithium overdose. He was monitored for 24 hours, and then
      renal replacement therapy was initiated after assessment by the renal team. As
      soon as the lithium level returned to normal therapeutic levels (from 4.7 mEq/L
      to 0.67 mEq/L), lithium was restarted by the medical team. At this point, the
      patient developed new slurred speech and later catatonia. In this case report, we
      discuss the factors that could determine which patients are at risk of
      neurotoxicity following lithium overdose and the appropriate decision regarding
      when and how to consider initiation of renal replacement therapy and restarting
      of lithium.

PMID- 29070625
TI  - Individualized tracking of self-directed motor learning in group-housed mice
      performing a skilled lever positioning task in the home cage.
AB  - Skilled forelimb function in mice is traditionally studied through behavioral
      paradigms that require extensive training by investigators and are limited by the
      number of trials individual animals are able to perform within a supervised
      session. We developed a skilled lever positioning task that mice can perform
      within their home cage. The task requires mice to use their forelimb to precisely
      hold a lever mounted on a rotary encoder within a rewarded position to dispense a
      water reward. A Raspberry Pi microcomputer is used to record lever position
      during trials and to control task parameters, thus making this low-footprint
      apparatus ideal for use within animal housing facilities. Custom Python software
      automatically increments task difficulty by requiring a longer hold duration, or
      a more accurate hold position, to dispense a reward. The performance of
      individual animals within group-housed mice is tracked through radio-frequency
      identification implants, and data stored on the microcomputer may be accessed
      remotely through an active internet connection. Mice continuously engage in the
      task for over 2.5 mo and perform ~500 trials/24 h. Mice required ~15,000 trials
      to learn to hold the lever within a 10 degrees  range for 1.5 s and were able to
      further refine movement accuracy by limiting their error to a 5 degrees  range
      within each trial. These results demonstrate the feasibility of autonomously
      training group-housed mice on a forelimb motor task. This paradigm may be used in
      the future to assess functional recovery after injury or cortical reorganization
      induced by self-directed motor learning. NEW & NOTEWORTHY We developed a low-cost
      system for fully autonomous training of group-housed mice on a forelimb motor
      task. We demonstrate the feasibility of tracking both end-point, as well as
      kinematic performance of individual mice, with each performing thousands of
      trials over 2.5 mo. The task is run and controlled by a Raspberry Pi
      microcomputer, which allows for cages to be monitored remotely through an active
      internet connection.

PMID- 29070626
TI  - Momentary level of slow default mode network activity is associated with distinct
      propagation and connectivity patterns in the anesthetized mouse cortex.
AB  - Complex spatiotemporal changes of slow spontaneous activity occur in the form of
      propagating waves in the cortex, leading to the transient formation of a specific
      activation topography, followed by a transition in the topography. The
      topographies resemble the stimulation-induced activation patterns and the
      underlying structural projections, suggesting that they contain motifs of task
      related activation. However, little is known about how propagation-mediated
      transitions between topographies are structured in terms of functional
      connectivity. Therefore, we investigated whether specific topographies or regions
      are associated with transitions involving long-range connections and hub
      modulation. We hypothesized that the activity level of the default mode network
      (DMN) at a given topography would affect the pattern of upcoming transitions,
      since high activity levels of the DMN are a distinct feature of the brain at
      rest. Using mesoscale voltage-sensitive dye imaging in the cortex of lightly
      anesthetized mice, we revealed that momentary levels of DMN activity are
      associated with distinct patterns of activity propagation and functional
      connectivity. High levels of DMN activity led to activity propagation across
      secondary and association cortices, increasing the centrality of a main hub
      region, whereas low-level activity led to global, diffuse, yet efficient changes
      in functional connectivity. Furthermore, low levels of activity resulted in
      increased long-range connectivity between frontal and posterior regions of the
      cortex. Our results indicate that DMN activity is associated with functional
      connectivity and wave propagation patterns, raising the possibility that the DMN
      may be involved in the modulation of long-range information processing associated
      with upcoming transitions. NEW & NOTEWORTHY Using voltage-sensitive dye imaging
      with high spatiotemporal resolution, we have revealed that increased DMN activity
      is associated with activity propagation to secondary/association cortices,
      whereas decreased activity is associated with stronger long-range frontal
      posterior connections in the mouse cortex. Hub metric and global functional
      connectivity parameters were accompanied by activity level changes. These results
      indicate that the DMN may aid in modulating the structure of transitions.

PMID- 29070627
TI  - tDCS over the motor cortex improves lexical retrieval of action words in
      poststroke aphasia.
AB  - One-third of stroke survivors worldwide suffer from aphasia. Speech and language
      therapy (SLT) is considered effective in treating aphasia, but because of time
      constraints, improvements are often limited. Noninvasive brain stimulation is a
      promising adjuvant strategy to facilitate SLT. However, stroke might render
      "classical" language regions ineffective as stimulation sites. Recent work showed
      the effectiveness of motor cortex stimulation together with intensive naming
      therapy to improve outcomes in aphasia (Meinzer et al. 2016). Although that study
      highlights the involvement of the motor cortex, the functional aspects by which
      it influences language remain unclear. In the present study, we focus on the role
      of motor cortex in language, investigating its functional involvement in access
      to specific lexico-semantic (object vs. action relatedness) information in
      poststroke aphasia. To this end, we tested effects of anodal transcranial direct
      current stimulation (tDCS) to the left motor cortex on lexical retrieval in 16
      patients with poststroke aphasia in a sham-controlled, double-blind study design.
      Critical stimuli were action and object words, and pseudowords. Participants
      performed a lexical decision task, deciding whether stimuli were words or
      pseudowords. Anodal tDCS improved accuracy in lexical decision, especially for
      words with action-related content and for pseudowords with an "action-like"
      ending ( t15 = 2.65, P = 0.036), but not for words with object-related content
      and pseudowords with "object-like" characteristics. We show as a proof-of
      principle that the motor cortex may play a specific role in access to lexico
      semantic content. Thus motor-cortex stimulation may strengthen content-specific
      word-to-semantic concept associations during language treatment in poststroke
      aphasia. NEW & NOTEWORTHY The role of motor cortex (MC) in language processing
      has been debated in both health and disease. Recent work has suggested that MC
      stimulation together with speech and language therapy enhances outcomes in
      aphasia. We show that MC stimulation has a differential effect on object- and
      action-word processing in poststroke aphasia. We propose that MC stimulation may
      specifically strengthen word-to-semantic concept association in aphasia. Our
      results potentially provide a way to tailor therapies for language
      rehabilitation.

PMID- 29070628
TI  - Functional roles of three cues that provide nonsynaptic modes of communication in
      the brain: electromagnetic field, oxygen, and carbon dioxide.
AB  - The integrative actions of the brain depend on the exchange of information among
      its computational elements. Hence, this phenomenon plays the key role in driving
      the complex dynamics of the central nervous system, in which true computations
      interact with noncomputational dynamical processes to generate brain
      representations of the body and of the body in the external world, and hence the
      finalistic behavior of the organism. In this context, it should be pointed out
      that, besides the intercellular interactions mediated by classical
      electrochemical signals, other types of interactions, namely, "cues" and
      "coercions," also appear to be exploited by the system to achieve its function.
      The present review focuses mainly on cues present in the environment and on those
      produced by cells of the body, which "pervade" the brain and contribute to its
      dynamics. These cues can also be metabolic substrates, and, in most cases, they
      are of fundamental importance to brain function and the survival of the entire
      organism. Three of these highly pervasive cues will be analyzed in greater
      detail, namely, oxygen, carbon dioxide, and electromagnetic fields (EMF). Special
      emphasis will be placed on EMF, since several authors have suggested that these
      highly pervasive energy fluctuations may play an important role in the global
      integrative actions of the brain; hence, EMF signaling may transcend classical
      connectionist models of brain function. Thus the new concept of "broadcasted
      neuroconnectomics" has been introduced, which transcends the current connectomics
      view of the brain.

PMID- 29070629
TI  - Object maintenance beyond their visible parts in working memory.
AB  - Completion of a partially occluded object requires that a representation of the
      whole is constructed based on the information provided by the physically
      specified parts of the stimulus. Such processes of amodal completion rely on the
      generation and maintenance of a mental image that renders the completed object in
      visual working memory (VWM). The present study examined this relationship between
      VWM storage and processes of object completion. We recorded event-related
      potentials to track VWM maintenance by means of the contralateral delay activity
      (CDA) during a change detection task in which composite objects (notched shapes
      abutting an occluding shape) to be memorized were primed to induce either a
      globally completed object or a noncompleted, mosaic representation. The results
      revealed an effect of completion in VWM despite physically identical visual
      input: change detection was more accurate for completed compared with mosaic
      representations when observers were required to memorize two objects, and these
      differences were reduced with four memorized items. At the electrophysiological
      level, globally completed (vs. mosaic) objects gave rise to a corresponding
      increase in CDA amplitudes. These results indicate that although incorporating
      the occluded portions of the presented shapes requires mnemonic resources, the
      complete object representations thus formed in VWM improve change detection
      performance by providing a more simple, regular shape. Overall, these findings
      demonstrate that mechanisms of object completion modulate VWM, with the memory
      load being determined by the structured representations of the memorized stimuli.
      NEW & NOTEWORTHY This study shows that completion of partially occluded objects
      requires visual working memory (VWM) resources. In the experiment reported, we
      induced observers to memorize a given visual input either as completed or as
      noncompleted objects. The results revealed both a behavioral performance
      advantage for completed vs. noncompleted objects despite physically identical
      input, and an associated modulation of an electrophysiological component that
      reflects VWM object retention, thus indicating that constructing an integrated
      object consumes mnemonic resources.

PMID- 29070630
TI  - Experience-dependent trends in CA1 theta and slow gamma rhythms in freely
      behaving mice.
AB  - CA1 place cells become more anticipatory with experience, an effect thought to be
      caused by NMDA receptor-dependent plasticity in the CA3-CA1 network. Theta (~5-12
      Hz), slow gamma (~25-50 Hz), and fast gamma (~50-100 Hz) rhythms are thought to
      route spatial information in the hippocampal formation and to coordinate place
      cell ensembles. Yet, it is unknown whether these rhythms exhibit experience
      dependent changes concurrent with those observed in place cells. Slow gamma
      rhythms are thought to indicate inputs from CA3 to CA1, and such inputs are
      thought to be strengthened with experience. Thus, we hypothesized that slow gamma
      rhythms would become more evident with experience. We tested this hypothesis
      using mice freely traversing a familiar circular track for three 10-min sessions
      per day. We found that slow gamma amplitude was reduced in the early minutes of
      the first session of each day, even though both theta and fast gamma amplitudes
      were elevated during this same period. However, in the first minutes of the
      second and third sessions of each day, all three rhythms were elevated.
      Interestingly, theta was elevated to a greater degree in the first minutes of the
      first session than in the first minutes of later sessions. Additionally, all
      three rhythms were strongly influenced by running speed in dynamic ways, with the
      influence of running speed on theta and slow gamma changing over time within and
      across sessions. These results raise the possibility that experience-dependent
      changes in hippocampal rhythms relate to changes in place cell activity that
      emerge with experience. NEW & NOTEWORTHY We show that CA1 theta, slow gamma, and
      fast gamma rhythms exhibit characteristic changes over time within sessions in
      familiar environments. These effects in familiar environments evolve across
      repeated sessions.

PMID- 29070631
TI  - The Kolliker-Fuse nucleus orchestrates the timing of expiratory abdominal nerve
      bursting.
AB  - Coordination of respiratory pump and valve muscle activity is essential for
      normal breathing. A hallmark respiratory response to hypercapnia and hypoxia is
      the emergence of active exhalation, characterized by abdominal muscle pumping
      during the late one-third of expiration (late-E phase). Late-E abdominal activity
      during hypercapnia has been attributed to the activation of expiratory neurons
      located within the parafacial respiratory group (pFRG). However, the mechanisms
      that control emergence of active exhalation, and its silencing in restful
      breathing, are not completely understood. We hypothesized that inputs from the
      Kolliker-Fuse nucleus (KF) control the emergence of late-E activity during
      hypercapnia. Previously, we reported that reversible inhibition of the KF reduced
      postinspiratory (post-I) motor output to laryngeal adductor muscles and brought
      forward the onset of hypercapnia-induced late-E abdominal activity. Here we
      explored the contribution of the KF for late-E abdominal recruitment during
      hypercapnia by pharmacologically disinhibiting the KF in in situ decerebrate
      arterially perfused rat preparations. These data were combined with previous
      results and incorporated into a computational model of the respiratory central
      pattern generator. Disinhibition of the KF through local parenchymal
      microinjections of gabazine (GABAA receptor antagonist) prolonged vagal post-I
      activity and inhibited late-E abdominal output during hypercapnia. In silico, we
      reproduced this behavior and predicted a mechanism in which the KF provides
      excitatory drive to post-I inhibitory neurons, which in turn inhibit late-E
      neurons of the pFRG. Although the exact mechanism proposed by the model requires
      testing, our data confirm that the KF modulates the formation of late-E abdominal
      activity during hypercapnia. NEW & NOTEWORTHY The pons is essential for the
      formation of the three-phase respiratory pattern, controlling the inspiratory
      expiratory phase transition. We provide functional evidence of a novel role for
      the Kolliker-Fuse nucleus (KF) controlling the emergence of abdominal expiratory
      bursts during active expiration. A computational model of the respiratory central
      pattern generator predicts a possible mechanism by which the KF interacts
      indirectly with the parafacial respiratory group and exerts an inhibitory effect
      on the expiratory conditional oscillator.

PMID- 29070634
TI  - Six-legged walking in insects: how CPGs, peripheral feedback, and descending
      signals generate coordinated and adaptive motor rhythms.
AB  - Walking is a rhythmic locomotor behavior of legged animals, and its underlying
      mechanisms have been the subject of neurobiological research for more than 100
      years. In this article, we review relevant historical aspects and contemporary
      studies in this field of research with a particular focus on the role of central
      pattern generating networks (CPGs) and their contribution to the generation of
      six-legged walking in insects. Aspects of importance are the generation of single
      leg stepping, the generation of interleg coordination, and how descending signals
      influence walking. We first review how CPGs interact with sensory signals from
      the leg in the generation of leg stepping. Next, we summarize how these
      interactions are modified in the generation of motor flexibility for forward and
      backward walking, curve walking, and speed changes. We then review the present
      state of knowledge with regard to the role of CPGs in intersegmental coordination
      and how CPGs might be involved in mediating descending influences from the brain
      for the initiation, maintenance, modification, and cessation of the motor output
      for walking. Throughout, we aim to specifically address gaps in knowledge, and we
      describe potential future avenues and approaches, conceptual and methodological,
      with the latter emphasizing in particular options arising from the advent of
      neurogenetic approaches to this field of research and its combination with
      traditional approaches.

PMID- 29070633
TI  - Central pattern generators in the turtle spinal cord: selection among the forms
      of motor behaviors.
AB  - Neuronal networks in the turtle spinal cord have considerable computational
      complexity even in the absence of connections with supraspinal structures. These
      networks contain central pattern generators (CPGs) for each of several behaviors,
      including three forms of scratch, two forms of swim, and one form of flexion
      reflex. Each behavior is activated by a specific set of cutaneous or electrical
      stimuli. The process of selection among behaviors within the spinal cord has
      multisecond memories of specific motor patterns. Some spinal cord interneurons
      are partially shared among several CPGs, whereas other interneurons are active
      during only one type of behavior. Partial sharing is a proposed mechanism that
      contributes to the ability of the spinal cord to generate motor pattern blends
      with characteristics of multiple behaviors. Variations of motor patterns, termed
      deletions, assist in characterization of the organization of the pattern
      generating components of CPGs. Single-neuron recordings during both normal and
      deletion motor patterns provide support for a CPG organizational structure with
      unit burst generators (UBGs) whose members serve a direction of a specific degree
      of freedom of the hindlimb, e.g., the hip-flexor UBG, the hip-extensor UBG, the
      knee-flexor UBG, the knee-extensor UBG, etc. The classic half-center hypothesis
      that includes all the hindlimb flexors in a single flexor half-center and all the
      hindlimb extensors in a single extensor half-center lacks the organizational
      complexity to account for the motor patterns produced by turtle spinal CPGs. Thus
      the turtle spinal cord is a valuable model system for studies of mechanisms
      responsible for selection and generation of motor behaviors. NEW & NOTEWORTHY The
      concept of the central pattern generator (CPG) is a major tenet in motor
      neuroethology that has influenced the design and interpretations of experiments
      for over a half century. This review concentrates on the turtle spinal cord and
      describes studies from the 1970s to the present responsible for key developments
      in understanding the CPG mechanisms responsible for the selection and production
      of coordinated motor patterns during turtle hindlimb motor behaviors.

PMID- 29070635
TI  - Prevalence of key breastfeeding indicators in 29 sub-Saharan African countries: a
      meta-analysis of demographic and health surveys (2010-2015).
AB  - OBJECTIVES: To carry out a meta-analysis to assess the prevalence of four key
      breastfeeding indicators in four subregions of 29 sub-Saharan African countries.
      DESIGN, SETTINGS AND PARTICIPANTS: The 29 countries were categorised into four
      subregions, and using cross-sectional data from the most recent Demographic and
      Health Surveys (2010-2015) of these countries prevalence of each of four key
      breastfeeding indicators was estimated for each of the subregions by carrying out
      a meta-analysis. Due to the presence of significant heterogeneity among the
      various surveys (I2>50%), a random-effect analytic model was used, and
      sensitivity analysis was performed to examine the effects of outliers. MAIN
      OUTCOME VARIABLES: Early initiation of breast feeding, exclusive breast feeding,
      predominant breast feeding and bottle feeding. RESULTS: The overall prevalence of
      early initiation of breast feeding varied between a lowest of 37.84% (95% CI
      24.62 to 51.05) in Central Africa to a highest of 69.31% (95% CI 67.65 to 70.97)
      in Southern Africa; the overall prevalence of exclusive breast feeding ranged
      between a lowest of 23.70% (95% CI 5.37 to 42.03) in Central Africa to a highest
      of 56.57% (95% CI 53.50 to 59.95) in Southern Africa; the overall prevalence of
      predominant breast feeding ranged between a lowest of 17.63% (95% CI 12.70 to
      22.55) in East Africa and a highest of 46.37% (95% CI 37.22 to 55.52) in West
      Africa; while the prevalence of bottle feeding varied between a lowest of 8.17%
      (95% CI 5.51 to 10.84) in West Africa and a highest of 30.05% (95% CI 28.42 to
      31.69) in Southern Africa. CONCLUSIONS: West Africa and Central Africa recorded
      lower overall prevalence of early initiation of breast feeding and exclusive
      breast feeding than the WHO's recommended target of 50% by the year 2025.
      Intervention for improved breastfeeding practices in sub-Saharan Africa should
      target West and Central Africa, while intervention to minimise bottle feeding
      should target Southern Africa.

PMID- 29070632
TI  - Retracing your footsteps: developmental insights to spinal network plasticity
      following injury.
AB  - During development of the spinal cord, a precise interaction occurs between
      descending projections and sensory afferents, with spinal networks that lead to
      expression of coordinated motor output. In the rodent, during the last embryonic
      week, motor output first occurs as regular bursts of spontaneous activity,
      progressing to stochastic patterns of episodes that express bouts of coordinated
      rhythmic activity perinatally. Locomotor activity becomes functionally mature in
      the 2nd postnatal wk and is heralded by the onset of weight-bearing locomotion on
      the 8th and 9th postnatal day. Concomitantly, there is a maturation of intrinsic
      properties and key conductances mediating plateau potentials. In this review, we
      discuss spinal neuronal excitability, descending modulation, and afferent
      modulation in the developing rodent spinal cord. In the adult, plastic mechanisms
      are much more constrained but become more permissive following neurotrauma, such
      as spinal cord injury. We discuss parallel mechanisms that contribute to
      maturation of network function during development to mechanisms of pathological
      plasticity that contribute to aberrant motor patterns, such as spasticity and
      clonus, which emerge following central injury.

PMID- 29070636
TI  - Correlates of mobile screen media use among children aged 0-8: a systematic
      review.
AB  - OBJECTIVE: This study is a systematic review of the peer-reviewed literature to
      identify the correlates of mobile screen media use among children aged 8 years
      and less. SETTING: Home or community-based studies were included in this review
      while child care or school-based studies were excluded. PARTICIPANTS: Children
      aged 8 years or less were the study population. Studies that included larger age
      groups without subgroup analysis specific to the 0-8 years category were
      excluded. Eight electronic databases were searched for peer-reviewed English
      language primary research articles published or in press between January 2009 and
      March 2017 that have studied correlates of mobile screen media use in this age
      group. OUTCOME MEASURE: Mobile screen media use was the primary outcome measure.
      Mobile screen media use refers to children's use of mobile screens, such as
      mobile phones, electronic tablets, handheld computers or personal digital
      assistants. RESULTS: Thirteen studies meeting the inclusion criteria were
      identified of which a total of 36 correlates were examined. Older children,
      children better skilled in using mobile screen media devices, those having
      greater access to such devices at home and whose parents had high mobile screen
      media use were more likely to have higher use of mobile screen media devices. No
      association existed with parent's age, sex and education. CONCLUSION: Limited
      research has been undertaken into young children's mobile screen media use and
      most of the variables have been studied too infrequently for robust conclusions
      to be reached. Future studies with objective assessment of mobile screen media
      use and frequent examination of the potential correlates across multiple studies
      and settings are recommended. TRIAL REGISTRATION NUMBER: This review is
      registered with PROSPERO International Prospective Register of Ongoing Systematic
      Reviews (registration number: CRD42015028028).

PMID- 29070637
TI  - Effects of photobiomodulation therapy in patients with chronic non-specific low
      back pain: protocol for a randomised placebo-controlled trial.
AB  - INTRODUCTION: Low back pain (LBP) is one of the largest and most frequent public
      health problems worldwide. Photobiomodulation therapy (PBMT) is a frequently used
      non-pharmacological therapy for the treatment of musculoskeletal disorders.
      However, there is little high-quality scientific evidence that demonstrates the
      effectiveness of PBMT in the treatment of patients with chronic LBP in the short,
      medium and long term. Therefore, the objective of this clinical trial is to
      evaluate the effects of PBMT in patients with chronic non-specific LBP in the
      short, medium and long term. METHODS AND ANALYSES: This is a prospectively
      registered, two-arm randomised placebo-controlled trial with blinded patients,
      assessors and treatment providers. One hundred and forty-eight patients with
      chronic non-specific LBP will be recruited. Treatment sessions will be provided
      three times a week for 4 weeks (totaling 12 sessions) with patients receiving
      either placebo or active PBMT. For ethical reasons, all patients, regardless of
      treatment allocation, will also receive an information booklet based on 'The Back
      Book'. Clinical outcomes will be measured at baseline, at the end of treatment,
      as well as 3, 6 and 12 months after randomisation. The primary outcomes will be
      pain intensity and disability measured after 12 sessions of treatment. The
      secondary outcomes will be pain intensity and disability measured at 3, 6 and 12
      months after randomisation, in addition to specific disability and global
      perceived effect in all time points. ETHICS AND DISSEMINATION: The study was
      approved by the Research Ethics Committee of Universidade Cidade de Sao Paulo.
      The results will be disseminated through scientific publications and
      presentations at national and international scientific meetings. TRIAL
      REGISTRATION NUMBER: NCT03089424.

PMID- 29070638
TI  - HPV knowledge, burden and genital wart location among heterosexually identified
      versus homosexually identified men who have sex with men in Lima, Peru: cross
      sectional results from a cohort study.
AB  - OBJECTIVES: The relationship between sexual practices, identity and role among
      Latino men who have sex with men (MSM) and HIV risk is the subject of ongoing
      investigation but less is known about how these aspects of sexuality relate to
      human papilloma-virus (HPV), an independent risk factor for HIV. This
      observational study investigated the relationship between HPV and sexual
      practices, identity and role as well as other sexually transmitted infection
      (STI)/HIV risk factors among HIV-negative heterosexually and homosexually
      identified Peruvian MSM. SETTING: Community-based clinic for MSM in Lima, Peru.
      PARTICIPANTS: 756 subjects were screened based on inclusion criteria of: born
      anatomically male; age >=18 years; had any anal intercourse with a man during the
      previous 12 months; residing in metropolitan Lima; HIV negative; willing to
      commit to twice-yearly clinic visits for 24 months; had not participated in an
      HIV or HPV vaccine study. 600/756 participants met the inclusion criteria and
      were enrolled, of whom 48% (284) identified as homosexual and 10% (57) as
      heterosexual, the basis of the analyses performed. RESULTS: Compared with
      homosexually identified MSM, heterosexually identified MSM had completed fewer
      years of formal education and were less likely to have: anogenital HPV or visible
      anal warts; given oral sex to a man; or used a condom with their most recent
      female sexual partner (all p<0.05). Conversely, heterosexually identified MSM
      were more likely to have: visible penile warts; used a condom during last anal
      intercourse; smoked cigarettes; had transactional sex; and used drugs during sex
      in the previous month (all p<0.01). There was no difference found between
      heterosexually and homosexually identified MSM by syphilis or high-risk HPV
      prevalence. CONCLUSIONS: HPV burden, wart type (penile vs anal) and select
      HIV/STI risk behaviours differed between heterosexually and homosexually
      identified Peruvian MSM. Understanding the implications of these differences can
      lead to tailored HIV/STI prevention interventions for heterosexually identified
      MSM. TRIAL REGISTRATION NUMBER: NCT01387412.

PMID- 29070640
TI  - Does the behavioural type-specific approach for type 2 diabetes promote changes
      in lifestyle? Protocol of a cluster randomised trial in Japan.
AB  - INTRODUCTION: Type 2 diabetes (T2D) is a significant problem, and lifestyle
      modifications including self-management are important. We have developed a
      structured individual-based lifestyle education (SILE) programme for T2D. With
      attention now being paid to techniques to change behaviour, we recently developed
      a behavioural type-specific SILE (BETSILE) programme. We aimed to evaluate the
      effectiveness of the BETSILE programme compared with the SILE programme for
      reducing glycated haemoglobin (HbA1c) in patients with T2D and special
      behavioural types by a cluster randomised controlled trial. METHODS AND ANALYSIS:
      This is a 6-month cluster randomised controlled trial with two intervention arms
      (BETSILE vs SILE) provided in a medical care setting by randomising registered
      dietitians for patients with T2D aged 20-79 years. Patients' behavioural types
      were classified into four types (BT1 to BT4) using an assessment sheet. We will
      perform independent trials for BT1 and BT2. The primary endpoint is a change from
      the baseline HbA1c value at 6 months. Differences between the SILE and BETSILE
      groups will be primarily analysed following the intention-to-treat principle.
      Crude and multivariate adjusted effects will be examined after adjusting for
      covariates, using a general linear mixed-effects model for continuous variables
      and a logistic regression mixed-effects model for dichotomous variables. Sample
      sizes needed were calculated assuming effect sizes of 0.42 and 0.33 for BT1 and
      BT2, respectively, an intraclass correlation of 0.02, a significance level of 5%
      (two-sided), a power of 80%, and equal allocation of clusters to the two arms,
      with each cluster having three BT1 patients for the SILE and BETSILE arms and six
      BT2 patients for the SILE and BETSILE arms. We will need 16 dietitians for each
      arm, and a total 288 patients will be required. ETHICS AND DISSEMINATION: This
      study has been approved by the Medical Ethical Committee of Teikyo University
      (No.15-222). Findings will be disseminated widely through peer-reviewed
      publications, etc. TRIAL REGISTRATION NUMBER: UMIN 000023087; Pre-results.

PMID- 29070639
TI  - Effects of a multicomponent workplace intervention programme with environmental
      changes on physical activity among Japanese white collar employees: a protocol
      for a cluster randomised controlled trial.
AB  - INTRODUCTION: Physical activity is one of the most important health behaviours as
      a determinant of physical and mental health. Although intervention strategies for
      promoting physical activity among workers are needed, evidence for the
      effectiveness of multilevel workplace interventions with environmental changes on
      the promotion of physical activity are still limited due to lack of cluster
      randomised controlled trials (RCTs). The aim of this study is to investigate
      effects of a 3-month workplace intervention programme with environmental changes
      on the improvement in physical activity among Japanese white collar employees.
      METHODS AND ANALYSIS: This study will be a two-arm and parallel-group cluster
      (worksite) RCT. Japanese worksites and employees who are employed by the
      worksites will be recruited through health insurance associations and chambers of
      commerce. Worksites that meet the inclusion criteria will be randomly allocated
      to intervention or control groups. The intervention worksites will be offered the
      original intervention programme that consists of 13 contents with environmental
      changes. The control worksites will be able to get three times feedback of the
      assessment of the amount of physical activity and basic occupational health
      service in each worksite. The primary outcome will be the total amount of
      physical activity measured by the Global Physical Activity Questionnaire at
      baseline, 3 months and 6 months. Multilevel latent growth modelling will be
      conducted to examine the effectiveness of the intervention programme. ETHICS AND
      DISSEMINATION: This study was ethically approved by the research ethics committee
      of the Graduate School of Medicine and Faculty of Medicine, The University of
      Tokyo, Japan (No. 11230). Results will be submitted and published in a scientific
      peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000024069; Pre-results.

PMID- 29070642
TI  - Exploring the theory, barriers and enablers for patient and public involvement
      across health, social care and patient safety: a protocol for a systematic review
      of reviews.
AB  - INTRODUCTION: The emergence of patient and public involvement (PPI) in healthcare
      in the UK can be traced as far back as the 1970s. More recently, campaigns by
      harmed patients and their relatives have emerged as a result of clinical failings
      in the NHS, challenging paternalistic healthcare, which have led to a new focus
      on PPI in quality and safety, nationally and internationally. Evidence suggests
      that PPI within patient safety is often atheoretical and located within a
      biomedical discourse. This review will explore the literature on PPI across
      patient safety, healthcare and social care to identify theory, barriers and
      enablers that can be used to develop PPI in patient safety. METHODS AND ANALYSIS:
      Systematic searches of three electronic bibliographic databases will be
      conducted, using both MeSH and free-text terms to identify empirical literature
      published from database inception to May 2017. The screening process will involve
      input from at least two researchers and any disagreement will be resolved through
      discussion with a third reviewer. Initial inclusion and exclusion criteria have
      been developed and will be refined iteratively throughout the process. Data
      extraction from included articles will be conducted by at least two researchers
      using a data extraction form. Extracted information will be analysed using a
      narrative review approach, which synthesises data using a descriptive method.
      ETHICS AND DISSEMINATION: No ethical approval is required for this review as no
      empirical data were collected. We believe that the findings and recommendations
      from this review will be particularly relevant for an audience of academics and
      policymakers. The findings will, therefore, be written up and disseminated in
      international peer-reviewed journals and academic conferences with a health
      focus. They will also be disseminated to leading health policy organisations in
      the NHS, such as NHS England and NHS Improvement and national policy bodies such
      as the Health Foundation.

PMID- 29070641
TI  - Dementia Population Risk Tool (DemPoRT): study protocol for a predictive
      algorithm assessing dementia risk in the community.
AB  - INTRODUCTION: The burden of disease from dementia is a growing global concern as
      incidence increases dramatically with age, and average life expectancy has been
      increasing around the world. Planning for an ageing population requires reliable
      projections of dementia prevalence; however, existing population projections are
      simple and have poor predictive accuracy. The Dementia Population Risk Tool
      (DemPoRT) will predict incidence of dementia in the population setting using
      multivariable modelling techniques and will be used to project dementia
      prevalence. METHODS AND ANALYSIS: The derivation cohort will consist of elderly
      Ontario respondents of the Canadian Community Health Survey (CCHS) (2001, 2003,
      2005 and 2007; 18 764 males and 25 288 females). Prespecified predictors include
      sociodemographic, general health, behavioural, functional and health condition
      variables. Incident dementia will be identified through individual linkage of
      survey respondents to population-level administrative healthcare databases (1797
      and 3281 events, and 117 795 and 166 573 person-years of follow-up, for males and
      females, respectively, until 31 March 2014). Using time of first dementia capture
      as the primary outcome and death as a competing risk, sex-specific proportional
      hazards regression models will be estimated. The 2008/2009 CCHS survey will be
      used for validation (approximately 4600 males and 6300 females). Overall
      calibration and discrimination will be assessed as well as calibration within
      predefined subgroups of importance to clinicians and policy makers. ETHICS AND
      DISSEMINATION: Research ethics approval has been granted by the Ottawa Health
      Science Network Research Ethics Board. DemPoRT results will be submitted for
      publication in peer-review journals and presented at scientific meetings. The
      algorithm will be assessable online for both population and individual uses.
      TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03155815, pre-results.

PMID- 29070643
TI  - Cast versus functional brace in the rehabilitation of patients treated non
      operatively for a rupture of the Achilles tendon: protocol for the UK study of
      tendo achilles rehabilitation (UK STAR) multi-centre randomised trial.
AB  - INTRODUCTION: Achilles tendon rupture affects over 11 000 people yearly in the
      UK, and the incidence is increasing. Controversy remains with regard to the best
      rehabilitation strategy for these patients. In operatively treated patients,
      functional bracing provides better outcomes compared with plaster casts. However,
      the role of functional bracing in non-operatively managed patients is unclear.
      This is the protocol for a multicentre randomised trial of plaster cast
      immobilisation versus functional bracing for patients with a non-operatively
      managed Achilles tendon rupture. METHODS AND ANALYSIS: All adults presenting with
      a primary rupture of the Achilles tendon will be screened. Non-operatively
      treated patients will be eligible to take part in the trial. Broad eligibility
      criteria will ensure that the results of the study can be generalised to the
      wider patient population. Randomisation will be on a 1:1 basis. Both
      rehabilitation strategies are widely used within the National Health Service.
      Standardised protocols will be followed, and details of plaster material and
      brace will be as per the site's usual practice.A minimum of 330 patients will be
      randomised to obtain 90% power to detect a difference of 8 points in Achilles
      Tendon Total Rupture Score at 9 months. Quality of life and resource use will be
      collected at 3, 6 and 9 months. The differences between treatment groups will be
      assessed on an intention-to-treat basis. The results of the trial-based economic
      evaluation will be expressed in terms of incremental cost per quality-adjusted
      life-year gained. ETHICS AND DISSEMINATION: The National Research Ethic Committee
      approved this study on 18 March 2016 (16/SC/0109).The National Institute for
      Health Research Health Technology Assessment monograph and a manuscript to a peer
      reviewed journal will be submitted on completion of the trial (summer 2019). The
      results of this trial will substantially inform clinical practice on the clinical
      and cost-effectiveness of the treatment of this injury. This study has been
      registered on the International Standard Randomised Controlled Trial Number
      registry with reference no ISRCTN62639639.

PMID- 29070644
TI  - Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic
      features.
AB  - OBJECTIVE: To assess the clinicopathological and therapeutic features of patients
      with low (>=1000 to <10 000 Buhlmann Titre Units) (BTU), medium (10 000-70 000)
      or high (>=70 000) anti-myelin-associated glycoprotein (anti-MAG) antibody
      titres. METHODS: We retrospectively and prospectively analysed standardised
      report forms and medical records of 202 patients from 14 neuromuscular centres.
      RESULTS: Mean age at onset and mean time between symptom onset to last follow-up
      were respectively 62.6 years (25-91.4) and 8.4 years (0.3-33.3). Anti-MAG
      antibody titres at diagnosis were low, medium or high in 11%, 51% and 38% of
      patients. Patients presented with monoclonal gammopathy of undetermined
      significance in 68% of cases. About 17% of patients presented with 'atypical'
      clinical phenotype independently of anti-MAG titres, including acute or chronic
      sensorimotor polyradiculoneuropathies (12.4%), and asymmetric or multifocal
      neuropathy (3%). At the most severe disease stage, 22.4% of patients were
      significantly disabled. Seventy-eight per cent of patients received
      immunotherapies. Transient clinical worsening was observed in 12% of patients
      treated with rituximab (11/92). Stabilisation after rituximab treatment during
      the 7-12-month follow-up period was observed in 29% of patients. Clinical
      response to rituximab during the 6-month and/or 7-12-month follow-up period was
      observed in 31.5% of patients and correlated with anti-MAG titre >=10 000 BTU.
      CONCLUSION: Our study highlights the extended clinical spectrum of patients with
      anti-MAG neuropathy, which appears unrelated to antibody titre. Besides, it may
      also suggest beneficial use of rituximab in the early phase of anti-MAG
      neuropathy.

PMID- 29070646
TI  - Amyloid-PET burden and regional distribution in cerebral amyloid angiopathy: a
      systematic review and meta-analysis of biomarker performance.
AB  - INTRODUCTION: We performed a meta-analysis to synthesise current evidence on
      amyloid-positron emission tomography (PET) burden and presumed preferential
      occipital distribution in sporadic cerebral amyloid angiopathy (CAA). METHODS: In
      a PubMed systematic search, we identified case-control studies with extractable
      data on global and occipital-to-global amyloid-PET uptake in symptomatic patients
      with CAA (per Boston criteria) versus control groups (healthy participants or
      patients with non-CAA deep intracerebral haemorrhage) and patients with
      Alzheimer's disease. To circumvent PET studies' methodological variation, we
      generated and used 'fold change', that is, ratio of mean amyloid uptake (global
      and occipital-to-global) of CAA relative to comparison groups. Amyloid-PET uptake
      biomarker performance was then quantified by random-effects meta-analysis on the
      ratios of the means. A ratio >1 indicates that amyloid-PET uptake (global or
      occipital/global) is higher in CAA than comparison groups, and a ratio <1
      indicates the reverse. RESULTS: Seven studies, including 106 patients with CAA
      (>90% with probable CAA) and 138 controls (96 healthy elderly, 42 deep
      intracerebral haemorrhage controls) and 72 patients with Alzheimer's disease,
      were included. Global amyloid-PET ratio between patients with CAA and controls
      was above 1, with an average effect size of 1.18 (95% CI 1.08 to 1.28; p<0.0001).
      Occipital-to-global amyloid-PET uptake ratio did not differ between patients with
      CAA versus patients with deep intracerebral haemorrhage or healthy controls. By
      contrast, occipital-to-global amyloid-PET uptake ratio was above 1 in patients
      with CAA versus those with Alzheimer's disease, with an average ratio of 1.10
      (95% CI 1.03 to 1.19; p=0.009) and high statistical heterogeneity. CONCLUSIONS:
      Our analysis provides exploratory actionable data on the overall effect sizes and
      strength of amyloid-PET burden and distribution in patients with CAA, useful for
      future larger studies.

PMID- 29070648
TI  - External ventricular drain-related infections: dilemmas of definitions,
      generalisability and associations versus causations.

PMID- 29070645
TI  - Prospective, multicentre study of external ventricular drainage-related
      infections in the UK and Ireland.
AB  - OBJECTIVES: External ventricular drain (EVD) insertion is a common neurosurgical
      procedure. EVD-related infection (ERI) is a major complication that can lead to
      morbidity and mortality. In this study, we aimed to establish a national ERI rate
      in the UK and Ireland and determine key factors influencing the infection risk.
      METHODS: A prospective multicentre cohort study of EVD insertions in 21
      neurosurgical units was performed over 6 months. The primary outcome measure was
      30-day ERI. A Cox regression model was used for multivariate analysis to
      calculate HR. RESULTS: A total of 495 EVD catheters were inserted into 452
      patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4-13). Of
      the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were
      plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an
      infection risk of 9.3%. Cox regression analysis demonstrated that factors
      independently associated with increased infection risk included duration of EVD
      placement for >=8 days (HR=2.47 (1.12-5.45); p=0.03), regular sampling (daily
      sampling (HR=4.73 (1.28-17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25
      12.38); p<0.01). There was no association between catheter type or tunnelling
      distance and ERI. CONCLUSIONS: In the UK and Ireland, the ERI rate was 9.3%
      during the study period. The study demonstrated that EVDs left in situ for >=8
      days and those sampled more frequently were associated with a higher risk of
      infection. Importantly, the study showed no significant difference in ERI risk
      between different catheter types.

PMID- 29070647
TI  - Non-office-hours admission affects intravenous thrombolysis treatment times and
      clinical outcome.

PMID- 29070649
TI  - Complex Immune Evasion Strategies in Classical Hodgkin Lymphoma.
AB  - The cellular microenvironment in classical Hodgkin lymphoma (cHL) is dominated by
      a mixed infiltrate of inflammatory cells with typically only about 1% Hodgkin and
      Reed/Sternberg (HRS) tumor cells. T cells are usually the largest population of
      cells in the cHL microenvironment, encompassing T helper (Th) cells, regulatory T
      cells (Tregs), and cytotoxic T cells. Th cells and Tregs presumably provide
      essential survival signals for HRS cells. Tregs are also involved in rescuing HRS
      cells from antitumor immune responses. An understanding of the immune evasion
      strategies of HRS cells is not only relevant for a characterization of the
      pathophysiology of cHL but is also clinically relevant, given the current
      treatment approaches targeting checkpoint inhibitors. Here, we characterized the
      cHL-specific CD4+ T-cell infiltrate regarding its role in immune evasion. Global
      gene expression analysis of CD4+ Th cells and Tregs isolated from cHL lymph nodes
      and reactive tonsils revealed that Treg signatures were enriched in CD4+ Th cells
      of cHL. Hence, HRS cells may induce Treg differentiation in Th cells, a
      conclusion supported by in vitro studies with Th cells and cHL cell lines. We
      also found evidence for immune-suppressive purinergic signaling and a role of the
      inhibitory receptor-ligand pairs B- and T-cell lymphocyte attenuator-herpesvirus
      entry mediator and CD200R-CD200 in promoting immune evasion. Taken together, this
      study highlights the relevance of Treg induction and reveals new immune
      checkpoint-driven immune evasion strategies in cHL. Cancer Immunol Res; 5(12);
      1122-32. (c)2017 AACR.

PMID- 29070650
TI  - Interleukin-12 from CD103+ Batf3-Dependent Dendritic Cells Required for NK-Cell
      Suppression of Metastasis.
AB  - Several host factors may affect the spread of cancer to distant organs; however,
      the intrinsic role of dendritic cells (DC) in controlling metastasis is poorly
      described. Here, we show in several tumor models that although the growth of
      primary tumors in Batf3-deficient mice, which lack cross-presenting DCs, was not
      different from primary tumors in wild-type (WT) control mice, Batf3-deficient
      mice had increased experimental and spontaneous metastasis and poorer survival.
      The increased metastasis was independent of CD4+ and CD8+ T lymphocytes, but
      required NK cells and IFNgamma. Chimeric mice in which Batf3-dependent DCs
      uniformly lacked the capacity to produce IL12 had metastatic burdens similar to
      the Batf3-deficient mice, suggesting that Batf3+ DCs were the only cell type
      whose IL12 production was critical for controlling metastasis. We found that IL12
      YFP reporter mice, whose lungs were injected with B16F10 melanoma, had increased
      numbers of IL12-expressing CD103+ DCs with enhanced CD86 expression. Bone-marrow
      derived DCs from WT, but not Batf3-deficient, mice activated NK cells to produce
      IFNgamma in an IL12-dependent manner and therapeutic injection of recombinant
      mouse IL12 decreased metastasis in both WT and Batf3-deficient mice. Analysis of
      TCGA datasets revealed an association between high expression of BATF3 and IRF8
      and improved survival of breast cancer patients; BATF3 expression also
      significantly correlated with NK-cell receptor genes, IL12, and IFNG
      Collectively, our findings show that IL12 from CD103+ DCs is critical for NK cell
      mediated control of tumor metastasis. Cancer Immunol Res; 5(12); 1098-108.
      (c)2017 AACR.

PMID- 29070651
TI  - Gene of the month: SDH.
AB  - Succinate dehydrogenase (SDH) is a heterotetrameric nuclear encoded mitochondrial
      protein complex which plays a role in the citric acid cycle and the electron
      transfer chain. Germline mutations in SDHA are associated with Leigh syndrome.
      Mutations in SDHB, SDHC and SDHD are found in an increasing number of neoplasms,
      most notably paragangliomas and wild-type gastrointestinal stromal tumours. SDH
      deficiency in these tumours has important prognostic implications, and also
      provides a novel target for molecular therapy. In this article, we outline the
      structure and function of SDH and provide a summary of its role in various
      diseases.

PMID- 29070652
TI  - 70 years of the JCP-highly cited papers: Proposals for the classification of
      chronic (mature) B and T lymphoid leukaemias.

PMID- 29070653
TI  - Rapid Detection of Carbapenemase Production in Enterobacteriaceae by Use of a
      Modified Paper Strip Carba NP Method.
AB  - Rapid and accurate detection of carbapenemase-producing Enterobacteriaceae (CPE)
      is important for preventing their spread in health care settings. We compared the
      performance of the Carba NP (CNP) test using the CLSI tube method with that using
      a modified paper strip method for the detection of carbapenemases in 390
      Enterobacteriaceae isolates. The isolates were identified by Hong Kong's
      carbapenem-resistant Enterobacteriaceae surveillance program in 2016 and
      comprised 213 CPE and 177 carbapenemase-negative Enterobacteriaceae isolates.
      Molecular genotype was used as the reference. The test results were read at
      different time points for the CLSI method (1 min, 5 min, 1 h, and 2 h) and strip
      method (1 min and 5 min). The strip CNP and CLSI CNP tests correctly detect
      carbapenemase production in 93% and 93% of KPC producers, 100% and 38% of IMI
      producers, 94% and 85% of IMP producers, 98% and 90% of NDM producers, and 29%
      and 12% of OXA producers, respectively. Overall, the strip method has superior
      sensitivity to the CLSI method (86% versus 75%, respectively; P < 0.001, McNemar
      test). The specificity of both methods was 100%. By the CLSI method, 27%, 14%,
      29%, and 6% of the CPE isolates were positive at 1 min, 5 min, 1 h, and 2 h,
      respectively. In contrast, by the strip method, 76% of the CPE isolates were
      positive at 1 min, and an additional 10% were positive at 5 min. In conclusion,
      the Carba NP test by use of the modified strip method has a higher sensitivity
      and a shorter assay time than that those by use of the CLSI tube method.

PMID- 29070654
TI  - Plague: Recognition, Treatment, and Prevention.
AB  - Plague is caused by Yersinia pestis and is not commonly encountered in clinics,
      although natural plague foci are widely distributed around the world. Y. pestis
      has been listed as a category A bioterrorism agent. A neglected diagnosis will
      cause severe consequences. Therefore, this minireview briefly introduces the
      current understanding on Y. pestis and then focuses on practical aspects of
      plague, including clinical manifestations, diagnosis, treatment, and prevention,
      to alert clinicians about this notorious disease.

PMID- 29070655
TI  - Evaluation of a Modified Carbapenem Inactivation Method for Detection of
      Carbapenemases in Pseudomonas aeruginosa.

PMID- 29070656
TI  - Molecular Diagnostics of Arthroconidial Yeasts, Frequent Pulmonary Opportunists.
AB  - Magnusiomyces capitatus and Saprochaete clavata are members of the clade of
      arthroconidial yeasts that represent emerging opportunistic pulmonary pathogens
      in immunocompromised patients. Given that standard ribosomal DNA (rDNA)
      identification often provides confusing results, in this study, we analyzed 34
      isolates with the goal of finding new genetic markers for classification using
      multilocus sequencing and amplified fragment length polymorphism (AFLP). The
      interspecific similarity obtained using rDNA markers (the internal transcribed
      spacer [ITS] and large subunit regions) was in the range of 96 to 99%, whereas
      that obtained using protein-coding loci (Rbp2, Act, and Tef1alpha) was lower at
      89.4 to 95.2%. Ultimately, Rbp2 was selected as the best marker for species
      distinction. On the basis of cloned ITS data, some strains proved to be
      misidentified in comparison with the identities obtained with phenotypic
      characters, protein sequences, and AFLP profiles, indicating that different
      copies of the ribosomal operon were present in a single species. Antifungal
      susceptibility testing revealed that voriconazole had the lowest MIC against M.
      capitatus, while amphotericin B had the lowest MIC against S. clavata Both
      species exhibited in vitro resistance to fluconazole and micafungin.

PMID- 29070657
TI  - Core Genome Multilocus Sequence Typing: a Standardized Approach for Molecular
      Typing of Mycoplasma gallisepticum.
AB  - Mycoplasma gallisepticum is the most virulent and economically important
      Mycoplasma species for poultry worldwide. Currently, M. gallisepticum strain
      differentiation based on sequence analysis of 5 loci remains insufficient for
      accurate outbreak investigation. Recently, whole-genome sequences (WGS) of many
      human and animal pathogens have been successfully used for microbial outbreak
      investigations. However, the massive sequence data and the diverse properties of
      different genes within bacterial genomes results in a lack of standard
      reproducible methods for comparisons among M. gallisepticum whole genomes. Here,
      we proposed the development of a core genome multilocus sequence typing (cgMLST)
      scheme for M. gallisepticum strains and field isolates. For development of this
      scheme, a diverse collection of 37 M. gallisepticum genomes was used to identify
      cgMLST targets. A total of 425 M. gallisepticum conserved genes (49.85% of M.
      gallisepticum genome) were selected as core genome targets. A total of 81 M.
      gallisepticum genomes from 5 countries on 4 continents were typed using M.
      gallisepticum cgMLST. Analyses of phylogenetic trees generated by cgMLST
      displayed a high degree of agreement with geographical and temporal information.
      Moreover, the high discriminatory power of cgMLST allowed differentiation between
      M. gallisepticum strains of the same outbreak. M. gallisepticum cgMLST represents
      a standardized, accurate, highly discriminatory, and reproducible method for
      differentiation among M. gallisepticum isolates. cgMLST provides stable and
      expandable nomenclature, allowing for comparison and sharing of typing results
      among laboratories worldwide. cgMLST offers an opportunity to harness the
      tremendous power of next-generation sequencing technology in applied avian
      mycoplasma epidemiology at both local and global levels.

PMID- 29070660
TI  - Ischemic lesions and superficial siderosis in CAA: Partners in crime or innocent
      bystanders?

PMID- 29070659
TI  - Serum neurofilament light in familial Alzheimer disease: A marker of early
      neurodegeneration.
AB  - OBJECTIVES: To investigate whether serum neurofilament light (NfL) concentration
      is increased in familial Alzheimer disease (FAD), both pre and post symptom
      onset, and whether it is associated with markers of disease stage and severity.
      METHODS: We recruited 48 individuals from families with PSEN1 or APP mutations to
      a cross-sectional study: 18 had symptomatic Alzheimer disease (AD) and 30 were
      asymptomatic but at 50% risk of carrying a mutation. Serum NfL was measured using
      an ultrasensitive immunoassay on the single molecule array (Simoa) platform.
      Cognitive testing and MRI were performed; 33 participants had serial MRI,
      allowing calculation of atrophy rates. Genetic testing established mutation
      status. A generalized least squares regression model was used to compare serum
      NfL among symptomatic mutation carriers, presymptomatic carriers, and
      noncarriers, adjusting for age and sex. Spearman coefficients assessed
      associations between serum NfL and (1) estimated years to/from symptom onset
      (EYO), (2) cognitive measures, and (3) MRI measures of atrophy. RESULTS: Nineteen
      of the asymptomatic participants were mutation carriers (mean EYO -9.6); 11 were
      noncarriers. Compared with noncarriers, serum NfL concentration was higher in
      both symptomatic (p < 0.0001) and presymptomatic mutation carriers (p = 0.007).
      Across all mutation carriers, serum NfL correlated with EYO (rho = 0.81, p <
      0.0001) and multiple cognitive and imaging measures, including Mini-Mental State
      Examination (rho = -0.62, p = 0.0001), Clinical Dementia Rating Scale sum of
      boxes (rho = 0.79, p < 0.0001), baseline brain volume (rho = -0.62, p = 0.0002),
      and whole-brain atrophy rate (rho = 0.53, p = 0.01). CONCLUSIONS: Serum NfL
      concentration is increased in FAD prior to symptom onset and correlates with
      measures of disease stage and severity. Serum NfL may thus be a feasible
      biomarker of early AD-related neurodegeneration.

PMID- 29070662
TI  - The new Neurology: Redesigns, short articles for print, full articles online, and
      data availability policies.

PMID- 29070661
TI  - Caudate nucleus as a component of networks controlling behavior.

PMID- 29070658
TI  - Sensory Repertoire of Bacterial Chemoreceptors.
AB  - Chemoreceptors in bacteria detect a variety of signals and feed this information
      into chemosensory pathways that represent a major mode of signal transduction.
      The five chemoreceptors from Escherichia coli have served as traditional models
      in the study of this protein family. Genome analyses revealed that many bacteria
      contain much larger numbers of chemoreceptors with broader sensory capabilities.
      Chemoreceptors differ in topology, sensing mode, cellular location, and, above
      all, the type of ligand binding domain (LBD). Here, we highlight LBD diversity
      using well-established and emerging model organisms as well as genomic surveys.
      Nearly a hundred different types of protein domains that are found in
      chemoreceptor sequences are known or predicted LBDs, but only a few of them are
      ubiquitous. LBDs of the same class recognize different ligands, and conversely,
      the same ligand can be recognized by structurally different LBDs; however, recent
      studies began to reveal common characteristics in signal-LBD relationships.
      Although signals can stimulate chemoreceptors in a variety of different ways,
      diverse LBDs appear to employ a universal transmembrane signaling mechanism.
      Current and future studies aim to establish relationships between LBD types, the
      nature of signals that they recognize, and the mechanisms of signal recognition
      and transduction.

PMID- 29070663
TI  - Neurofilaments in blood: (Almost) facing clinical application.

PMID- 29070664
TI  - Epidemiology of recurrent traumatic brain injury in the general population: A
      systematic review.
AB  - OBJECTIVE: To comprehensively assess recurrent traumatic brain injury (rTBI) risk
      and risk factors in the general population. METHODS: We systematically searched
      MEDLINE, EMBASE, and the references of included studies until January 16, 2017,
      for general population observational studies reporting rTBI risk or risk factors.
      Estimates were not meta-analyzed due to significant methodologic heterogeneity
      between studies, which was evaluated using meta-regression. RESULTS: Twenty-two
      studies reported recurrence risk and 11 reported on 27 potential risk factors.
      rTBI risk was heterogeneous and varied from 0.43% (95% confidence interval [CI]
      0.19%-0.67%) to 41.92% (95% CI 34.43%-49.40%), with varying follow-up periods (3
      days-55 years). Median time to recurrence ranged from 0.5 to 3.8 years. In
      studies where cases were ascertained from multiple points of care, at least 5.50%
      (95% CI 4.80%-6.30%) of patients experienced a recurrence after a 1-year follow
      up. Studies that used administrative data/self-report surveys to ascertain cases
      tended to report higher risk. Risk factors measured at time of index traumatic
      brain injury (TBI) that were significantly associated with rTBI in more than one
      study were male sex, prior TBI before index case, moderate or severe TBI, and
      alcohol intoxication. Risk factors reported in a single study that were
      significantly associated with rTBI were epilepsy, not seeking medical care, and
      multiple factors indicative of low socioeconomic status. CONCLUSIONS: rTBI is an
      important contributor to the general population TBI burden. Certain risk factors
      can help identify individuals at higher risk of these repeated injuries. However,
      higher quality research that improves on rTBI surveillance methodology is needed.

PMID- 29070665
TI  - Blood-brain barrier leakage increases with small vessel disease in acute ischemic
      stroke.
AB  - OBJECTIVE: In patients with acute ischemic stroke, we aimed to investigate the
      relation between preexisting small vessel disease (SVD) and the amount of blood
      brain barrier (BBB) leakage in ischemic and nonischemic area before IV
      thrombolysis. METHODS: We retrospectively accessed anonymous patient-level data
      from the Stroke Imaging Repository and the Virtual International Stroke Trials
      Archive resources and included patients treated with IV thrombolysis with
      pretreatment MRI. We rated SVD features using validated qualitative magnetic
      resonance (MR) scales. Leakage of BBB was assessed with postprocessing of
      perfusion-weighted images. We evaluated associations between SVD features
      (individually and summed in a global SVD score) and BBB leakage using linear
      regression analysis, adjusting for major clinical confounders. RESULTS: A total
      of 212 patients, mean age (+/-SD) 69.5 years (+/-16.1), 102 (48%) male, had
      available MR before IV thrombolysis. Evidence of BBB leakage was present in 175
      (80%) and 205 (94%) patients in the ischemic and nonischemic area, respectively.
      Lacunar infarcts (beta = 0.17, p = 0.042) were associated with BBB leakage in the
      ischemic area, and brain atrophy was associated with BBB leakage in both ischemic
      (beta = 0.20, p = 0.026) and nonischemic (beta = 0.27, p = 0.001) areas.
      Increasing SVD grade was independently associated with BBB leakage in both
      ischemic (beta = 0.26, p = 0.007) and nonischemic (beta = 0.27, p = 0.003) area.
      CONCLUSIONS: Global SVD burden is associated with increased BBB leakage in both
      acutely ischemic and nonischemic area. Our results support that SVD score has
      construct validity, and confirm a relation between SVD and BBB disruption also in
      patients with acute stroke.

PMID- 29070666
TI  - Multiparametric MRI changes persist beyond recovery in concussed adolescent
      hockey players.
AB  - OBJECTIVE: To determine whether multiparametric MRI data can provide insight into
      the acute and long-lasting neuronal sequelae after a concussion in adolescent
      athletes. METHODS: Players were recruited from Bantam hockey leagues in which
      body checking is first introduced (male, age 11-14 years). Clinical measures,
      diffusion metrics, resting-state network and region-to-region functional
      connectivity patterns, and magnetic resonance spectroscopy absolute metabolite
      concentrations were analyzed from an independent, age-matched control group of
      hockey players (n = 26) and longitudinally in concussed athletes within 24 to 72
      hours (n = 17) and 3 months (n = 14) after a diagnosed concussion. RESULTS: There
      were diffusion abnormalities within multiple white matter tracts, functional
      hyperconnectivity, and decreases in choline 3 months after concussion. Tract
      specific spatial statistics revealed a large region along the superior
      longitudinal fasciculus with the largest decreases in diffusivity measures, which
      significantly correlated with clinical deficits. This region also spatially
      intersected with probabilistic tracts connecting cortical regions where we found
      acute functional connectivity changes. Hyperconnectivity patterns at 3 months
      after concussion were present only in players with relatively less severe
      clinical outcomes, higher choline concentrations, and diffusivity indicative of
      relatively less axonal disruption. CONCLUSIONS: Changes persisted well after
      players' clinical scores had returned to normal and they had been cleared to
      return to play. Ongoing white matter maturation may make adolescent athletes
      particularly vulnerable to brain injury, and they may require extended recovery
      periods. The consequences of early brain injury for ongoing brain development and
      risk of more serious conditions such as second impact syndrome or neural
      degenerative processes need to be elucidated.

PMID- 29070668
TI  - Evolution of DWI lesions in cerebral amyloid angiopathy: Evidence for ischemia.
AB  - OBJECTIVE: To address the pathophysiologic nature of small diffusion-weighted
      imaging (DWI) lesions in patients with cerebral amyloid angiopathy (CAA) who
      underwent serial MRI. Specifically, we tested (1) whether DWI lesions occurred
      preferentially in individuals with prior DWI lesions, (2) the cross-sectional
      association with chronic cortical cerebral microinfarcts (CMIs), and (3) the
      evolution of DWI lesions over time. METHODS: Patients with probable CAA (n = 79)
      who underwent at least 2 MRI sessions were included. DWI lesions were assessed at
      each available time point. Lesion appearance and characteristics were assessed on
      available structural follow-up images. Presence and burden of other neuroimaging
      markers of small vessel disease (white matter hyperintensities, cerebral
      microbleeds, cortical superficial siderosis, and chronic cortical CMIs) were
      assessed as well. RESULTS: Among 221 DWI scans (79 patients with 2 DWI scans; 40
      with >=3), 60 DWI lesions were found in 28 patients. Patients with DWI lesions at
      baseline were not more likely to have additional DWI lesions on follow-up
      compared to patients without DWI lesions at baseline. DWI lesions were associated
      with chronic cortical CMIs and cortical superficial siderosis, but not with other
      markers. For 39/60 DWI lesions, >1 MRI sequence was available at follow-up to
      determine lesion evolution. Twenty-four (62%) were demarcated as chronic lesions
      on follow-up MRI. Five appeared as cavitations, 18 as noncavitated infarcts, and
      1 underwent hemorrhagic transformation. CONCLUSIONS: Based on their neuroimaging
      signature as well as their association with chronic cortical CMIs, DWI lesions
      appear to have an ischemic origin and represent one part of the CMI spectrum.

PMID- 29070669
TI  - Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: A
      prospective study.
AB  - OBJECTIVE: In order to explore the mechanisms of cortical superficial siderosis
      (cSS) multifocality and its clinical implications for recurrent intracerebral
      hemorrhage (ICH) risk in patients with cerebral amyloid angiopathy (CAA), we used
      a new rating method that we developed specifically to evaluate cSS extent at
      spatially separated foci. METHODS: Consecutive patients with CAA-related ICH
      according to Boston criteria from a single-center prospective cohort were
      analyzed. The new score that assesses cSS multifocality (total range 0-4) showed
      excellent interrater reliability (k = 0.87). The association of cSS with markers
      of CAA and acute ICH was investigated. Patients were followed prospectively for
      recurrent symptomatic ICH. RESULTS: The cohort included 313 patients with CAA.
      Multifocal cSS prevalence was 21.1%. APOE epsilon2 allele prevalence was higher
      in patients with multifocal cSS. In probable/definite CAA, cSS multifocality was
      independently associated with neuroimaging markers of CAA severity, including
      lobar microbleeds, but not with acute ICH features, which conversely, were
      determinants of cSS in possible CAA. During a median follow-up of 2.6 years
      (interquartile range 0.9-5.1 years), the annual ICH recurrence rates per cSS
      scores (0-4) were 5%, 6.5%, 13.5%, 16.2%, and 26.9%, respectively. cSS
      multifocality (presence and spread) was the only independent predictor of
      increased symptomatic ICH risk (hazard ratio 3.19; 95% confidence interval 1.77
      5.75; p < 0.0001). CONCLUSIONS: The multifocality of cSS correlates with disease
      severity in probable CAA; therefore cSS is likely to be caused by discrete
      hemorrhagic foci. The new cSS scoring system might be valuable for clinicians in
      determining annual risk of ICH recurrence.

PMID- 29070670
TI  - IFN-lambda4 Attenuates Antiviral Responses by Enhancing Negative Regulation of
      IFN Signaling.
AB  - Type III IFNs are important mediators of antiviral immunity. IFN-lambda4 is a
      unique type III IFN because it is produced only in individuals who carry a dG
      allele of a genetic variant rs368234815-dG/TT. Counterintuitively, those
      individuals who can produce IFN-lambda4, an antiviral cytokine, are also less
      likely to clear hepatitis C virus infection. In this study, we searched for
      unique functional properties of IFN-lambda4 that might explain its negative
      effect on hepatitis C virus clearance. We used fresh primary human hepatocytes
      (PHHs) treated with recombinant type III IFNs or infected with Sendai virus to
      model acute viral infection and subsequently validated our findings in HepG2 cell
      line models. Endogenous IFN-lambda4 protein was detectable only in Sendai virus
      infected PHHs from individuals with the dG allele, where it was poorly secreted
      but highly functional, even at concentrations < 50 pg/ml. IFN-lambda4 acted
      faster than other type III IFNs in inducing antiviral genes, as well as negative
      regulators of the IFN response, such as USP18 and SOCS1 Transient treatment of
      PHHs with IFN-lambda4, but not IFN-lambda3, caused a strong and sustained
      induction of SOCS1 and refractoriness to further stimulation with IFN-lambda3.
      Our results suggest unique functional properties of IFN-lambda4 that can be
      important in viral clearance and other clinical conditions.

PMID- 29070671
TI  - Complement Regulatory Protein Factor H Is a Soluble Prion Receptor That
      Potentiates Peripheral Prion Pathogenesis.
AB  - Several complement proteins exacerbate prion disease, including C3, C1q, and
      CD21/35. These proteins of the complement cascade likely increase uptake,
      trafficking, and retention of prions in the lymphoreticular system, hallmark
      sites of early prion propagation. Complement regulatory protein factor H (fH)
      binds modified host proteins and lipids to prevent C3b deposition and, thus,
      autoimmune cell lysis. Previous reports show that fH binds various conformations
      of the cellular prion protein, leading us to question the role of fH in prion
      disease. In this article, we report that transgenic mice lacking Cfh alleles
      exhibit delayed peripheral prion accumulation, replication, and pathogenesis and
      onset of terminal disease in a gene-dose manner. We also report a biophysical
      interaction between purified fH and prion rods enriched from prion-diseased
      brain. fH also influences prion deposition in brains of infected mice. We
      conclude from these data and previous findings that the interplay between
      complement and prions likely involves a complex balance of prion sequestration
      and destruction via local tissue macrophages, prion trafficking by B and
      dendritic cells within the lymphoreticular system, intranodal prion replication
      by B and follicular dendritic cells, and potential prion strain selection by
      CD21/35 and fH. These findings reveal a novel role for complement-regulatory
      proteins in prion disease.

PMID- 29070672
TI  - Broad Susceptibility of Nucleolar Proteins and Autoantigens to Complement C1
      Protease Degradation.
AB  - Anti-nuclear autoantibodies, which frequently target the nucleoli, are pathogenic
      hallmarks of systemic lupus erythematosus (SLE). Although the causes of these Abs
      remain broad and ill-defined, a genetic deficiency in C1 complex (C1qC1r2C1s2) or
      C4 is able to induce these Abs. Considering a recent finding that, in dead cells,
      nucleoli were targeted by C1q and two nucleolar autoantigens were degraded by
      C1r/C1s proteases, we considered that C1 could help protect against antinuclear
      autoimmunity by broadly degrading nucleolar proteins or autoantigens. Nucleoli
      were isolated to homogeneity and structurally defined. After C1 treatment,
      cleaved nucleolar proteins were identified by proteomic two-dimensional
      fluorescence difference gel electrophoresis and mass spectrometry, and further
      verified by Western blotting using specific Abs. The extent of nucleolar
      autoantigen degradation upon C1 treatment was estimated using SLE patient
      autoantibodies. The isolated nucleoli were broadly reactive with SLE patient
      autoantibodies. These nucleoli lacked significant autoproteolysis, but many
      nucleolar proteins and autoantigens were degraded by C1 proteases; >20 nucleolar
      proteins were identified as C1 cleavable. These were further validated by Western
      blotting using specific Abs. The broad autoantigenicity of the nucleoli may
      attribute to their poor autoproteolysis, causing autologous immune stimulation
      upon necrotic exposure. However, C1q targets at these nucleoli to cause C1
      protease activation and the cleavage of many nucleolar proteins or autoantigens.
      This may represent one important surveillance mechanism against antinuclear
      autoimmunity because C1 genetic deficiency causes anti-nuclear autoantibodies and
      SLE disease.

PMID- 29070674
TI  - Orchestrating Role of Apoptosis Inhibitor of Macrophage in the Resolution of
      Acute Lung Injury.
AB  - Appropriate resolution of inflammation is known to be essential in tissue
      homeostasis. In this study, we evaluated the significance of a macrophage-derived
      soluble protein, apoptosis inhibitor of macrophage (AIM), in LPS-induced lung
      injury in mice. After oropharyngeal administration of LPS, the level of free-form
      serum AIM increased on days 2-4, accompanied by the resolution of inflammation,
      which was observed in the cellular profile of bronchoalveolar lavage fluid. In an
      experiment using wild-type (WT) and AIM-/- mice, the resolution of inflammation
      was accelerated in AIM-/- mice when compared with the WT mice, which was reversed
      when recombinant AIM protein was administered. The changes in the
      histopathological findings and inflammatory mediators followed similar trends,
      and the ratio of apoptotic cells was increased in AIM-/- mice when compared with
      the WT mice. In vitro analysis showed that macrophage phagocytosis of apoptotic
      neutrophils was suppressed in the presence of AIM, indicating that anti
      resolution property of AIM involves efferocytosis inhibition. In lipidomic
      analysis of lung tissues, the levels of several lipid mediators increased
      markedly when LPS was given to WT mice. However, in AIM-/- mice, the
      concentrations of these lipid mediators were not significantly upregulated by
      LPS. These data reflect the significant role of AIM in lipid metabolism; it may
      suppress lipid metabolites at baseline, and then produce an
      inflammatory/pathologic pattern in the event of LPS-induced lung injury. Taken
      together, AIM may play an orchestrating role in the resolution process of
      inflammation by altering the profile of pulmonary lipid mediators in mice.

PMID- 29070673
TI  - IL-17A-Induced PLET1 Expression Contributes to Tissue Repair and Colon
      Tumorigenesis.
AB  - This study identifies a novel mechanism linking IL-17A with colon tissue repair
      and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue
      repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and
      markedly reduced tumor development in an azoxymethane/DSS model of colitis
      associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker
      involved in wound healing), was highly induced in DSS-treated colon tissues and
      tumors in an IL-17RC-dependent manner. PLET1 expression was induced in LGR5+
      colon epithelial cells after DSS treatment. LGR5+PLET1+ marks a highly
      proliferative cell population with enhanced expression of IL-17A target genes.
      PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium
      and reduced tumor formation in an azoxymethane/DSS model of colitis-associated
      cancer. Our results suggest that IL-17A-induced PLET1 expression contributes to
      tissue repair and colon tumorigenesis.

PMID- 29070675
TI  - Prevalence and general health status of people with intellectual disabilities in
      Scotland: a total population study.
AB  - BACKGROUND: Prevalence of intellectual disabilities varies considerably between
      studies. People with intellectual disabilities experience health inequalities,
      but most studies comprise small or incomplete populations. We investigated in a
      whole country population the (1) prevalence of intellectual disabilities and (2)
      general health status compared with the general population. METHOD: Data were
      from Scotland's Census, 2011. We calculated the prevalence of intellectual
      disabilities, reported general health status of people with and without
      intellectual disabilities and the extent of health-related limitations to daily
      activities. We conducted logistic regressions to determine the ORs of
      intellectual disabilities predicting poor health and associations with age and
      gender. RESULTS: Of Scotland's 5 295 403 population, 26 349 (0.5%) had
      intellectual disabilities; 15 149 (57.5%) were males and 11 200 (42.5%) were
      females; 5234 (0.6%) were children/youth (0-15) and 21 115 (0.5%) were adults (16
      75+ years). Identification of intellectual disabilities rises until age 5 years,
      with a further small rise by age 9 years. Children and adults with intellectual
      disabilities reported more poor health (47.9% and 40.3%) than the general
      population (2.1% and 13.8%) and were more limited in activities by their health.
      Intellectual disabilities had an OR of 43.2 (95% CI 40.8 to 45.7) in predicting
      poor health; the influence of increasing age on poor health was markedly
      interacted by presence of intellectual disabilities, likely to be due to a
      'healthy survivor' effect within the intellectual disabilities population.
      CONCLUSION: People with intellectual disabilities have poorer general health than
      other people, especially children and young people. Accurate information on
      population prevalence and health status is essential to plan appropriate
      resources.

PMID- 29070667
TI  - Alzheimer disease brain atrophy subtypes are associated with cognition and rate
      of decline.
AB  - OBJECTIVE: To test the hypothesis that cortical and hippocampal volumes, measured
      in vivo from volumetric MRI (vMRI) scans, could be used to identify variant
      subtypes of Alzheimer disease (AD) and to prospectively predict the rate of
      clinical decline. METHODS: Amyloid-positive participants with AD from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) 1 and ADNI2 with baseline MRI
      scans (n = 229) and 2-year clinical follow-up (n = 100) were included. AD
      subtypes (hippocampal sparing [HpSpMRI], limbic predominant [LPMRI], typical AD
      [tADMRI]) were defined according to an algorithm analogous to one recently
      proposed for tau neuropathology. Relationships between baseline hippocampal
      volume to cortical volume ratio (HV:CTV) and clinical variables were examined by
      both continuous regression and categorical models. RESULTS: When participants
      were divided categorically, the HpSpMRI group showed significantly more AD-like
      hypometabolism on 18F-fluorodeoxyglucose-PET (p < 0.05) and poorer baseline
      executive function (p < 0.001). Other baseline clinical measures did not differ
      across the 3 groups. Participants with HpSpMRI also showed faster subsequent
      clinical decline than participants with LPMRI on the Alzheimer's Disease
      Assessment Scale, 13-Item Subscale (ADAS-Cog13), Mini-Mental State Examination
      (MMSE), and Functional Assessment Questionnaire (all p < 0.05) and tADMRI on the
      MMSE and Clinical Dementia Rating Sum of Boxes (CDR-SB) (both p < 0.05). Finally,
      a larger HV:CTV was associated with poorer baseline executive function and a
      faster slope of decline in CDR-SB, MMSE, and ADAS-Cog13 score (p < 0.05). These
      associations were driven mostly by the amount of cortical rather than hippocampal
      atrophy. CONCLUSIONS: AD subtypes with phenotypes consistent with those observed
      with tau neuropathology can be identified in vivo with vMRI. An increased HV:CTV
      ratio was predictive of faster clinical decline in participants with AD who were
      clinically indistinguishable at baseline except for a greater dysexecutive
      presentation.

PMID- 29070676
TI  - Unique Maturation Trajectories of Basket and Chandelier Cells in the Neocortex.

PMID- 29070677
TI  - Overexpression of sphingosine-1-phosphate lyase protects insulin-secreting cells
      against cytokine toxicity.
AB  - Increasing evidence suggests a crucial role of inflammation in cytokine-mediated
      beta-cell dysfunction and death in type 1 diabetes mellitus, although the
      mechanisms are incompletely understood. Sphingosine 1-phosphate (S1P) is a
      multifunctional bioactive sphingolipid involved in the development of many
      autoimmune and inflammatory diseases. Here, we investigated the role of
      intracellular S1P in insulin-secreting INS1E cells by genetically manipulating
      the S1P-metabolizing enzyme S1P lyase (SPL). The expression of spl was down
      regulated by cytokines in INS1E cells and rat islets. Overexpression of SPL
      protected against cytokine toxicity. Interestingly, the SPL overexpression did
      not suppress the cytokine-induced NFkappaB-iNOS-NO pathway but attenuated calcium
      leakage from endoplasmic reticulum (ER) stores as manifested by lower cytosolic
      calcium levels, higher expression of the ER protein Sec61a, decreased
      dephosphorylation of Bcl-2-associated death promoter (Bad) protein, and weaker
      caspase-3 activation in cytokine-treated (IL-1beta, TNFalpha, and IFNgamma)
      cells. This coincided with reduced cytokine-mediated ER stress, indicated by
      measurements of CCAAT/enhancer-binding protein homologous protein (chop) and
      immunoglobulin heavy chain binding protein (bip) levels. Moreover, cytokine
      treated SPL-overexpressing cells exhibited increased expression of prohibitin 2
      (Phb2), involved in the regulation of mitochondrial assembly and respiration. SPL
      overexpressing cells were partially protected against cytokine-mediated ATP
      reduction and inhibition of glucose-induced insulin secretion. siRNA-mediated spl
      suppression resulted in effects opposite to those observed for SPL
      overexpression. Knockdown of phb2 partially reversed beneficial effects of SPL
      overexpression. In conclusion, the relatively low endogenous Spl expression level
      in insulin-secreting cells contributes to their extraordinary vulnerability to
      proinflammatory cytokine toxicity and may therefore represent a promising target
      for beta-cell protection in type 1 diabetes mellitus.

PMID- 29070678
TI  - DnaC, the indispensable companion of DnaB helicase, controls the accessibility of
      DnaB helicase by primase.
AB  - Former studies relying on hydrogen/deuterium exchange analysis suggest that DnaC
      bound to DnaB alters the conformation of the N-terminal domain (NTD) of DnaB to
      impair the ability of this DNA helicase to interact with primase. Supporting this
      idea, the work described herein based on biosensor experiments and enzyme-linked
      immunosorbent assays shows that the DnaB-DnaC complex binds poorly to primase in
      comparison with DnaB alone. Using a structural model of DnaB complexed with the C
      terminal domain of primase, we found that Ile-85 is located at the interface in
      the NTD of DnaB that contacts primase. An alanine substitution for Ile-85
      specifically interfered with this interaction and impeded DnaB function in DNA
      replication, but not its activity as a DNA helicase or its ability to bind to
      ssDNA. By comparison, substitutions of Asn for Ile-136 (I136N) and Thr for Ile
      142 (I142T) in a subdomain previously named the helical hairpin in the NTD of
      DnaB altered the conformation of the helical hairpin and/or compromised its
      pairwise arrangement with the companion subdomain in each brace of protomers of
      the DnaB hexamer. In contrast with the I85A mutant, the latter were defective in
      DNA replication due to impaired binding to both ssDNA and primase. In view of
      these findings, we propose that DnaC controls the ability of DnaB to interact
      with primase by modifying the conformation of the NTD of DnaB.

PMID- 29070679
TI  - The E3 ubiquitin ligase SCFFBXL14 complex stimulates neuronal differentiation by
      targeting the Notch signaling factor HES1 for proteolysis.
AB  - Molecular oscillators are important cellular regulators of, for example,
      circadian clocks, oscillations of immune regulators, and short-period (ultradian)
      rhythms during embryonic development. The Notch signaling factor HES1 (hairy and
      enhancer of split 1) is a well-known repressor of proneural genes, and HES1
      ultradian oscillation is essential for keeping cells in an efficiently
      proliferating progenitor state. HES1 oscillation is driven by both
      transcriptional self-repression and ubiquitin-dependent proteolysis. However, the
      E3 ubiquitin ligase targeting HES1 for proteolysis remains unclear. Based on
      siRNA-mediated gene silencing screening, co-immunoprecipitation, and
      ubiquitination assays, we discovered that the E3 ubiquitin ligase SCFFBXL14
      complex regulates HES1 ubiquitination and proteolysis. siRNA-mediated knockdown
      of the Cullin-RING E3 ubiquitin ligases RBX1 or CUL1 increased HES1 protein
      levels, prolonged its half-life, and dampened its oscillation. FBXL14, an F-box
      protein for SCF ubiquitin ligase, associates with HES1. FBXL14 silencing
      stabilized HES1, whereas FBXL14 overexpression decreased HES1 protein levels. Of
      note, the SCFFBXL14 complex promoted the ubiquitination of HES1 in vivo, and a
      conserved WRPW motif in HES1 was essential for HES1 binding to FBXL14 and for
      ubiquitin-dependent HES1 degradation. HES1 knockdown promoted neuronal
      differentiation, but FBXL14 silencing inhibited neuronal differentiation induced
      by HES1 ablation in mES and F9 cells. Our results suggest that SCFFBXL14 promotes
      neuronal differentiation by targeting HES1 for ubiquitin-dependent proteolysis
      and that the C-terminal WRPW motif in HES1 is required for this process.

PMID- 29070680
TI  - The allosteric glycogen synthase kinase-3 inhibitor NP12 limits myocardial
      remodeling and promotes angiogenesis in an acute myocardial infarction model.
AB  - A key feature of acute myocardial infarction (AMI) is an alteration in cardiac
      architecture. Signaling events that result in the inhibition of glycogen synthase
      kinase-3 (GSK-3)beta represent an adaptive response that might limit the extent
      of adverse remodeling in the aftermath of AMI. Here, we report that an allosteric
      inhibitor of GSK-3beta, 4-benzyl-2-(naphthalene-1-yl)-1,2,4-thiadiazolidine-3,5
      dione (NP12), lessens the magnitude of adverse myocardial remodeling and promotes
      angiogenesis. Male and female mice 8-10 weeks old were grouped (six animals in
      each group) into sham surgery (sham group), left anterior descending (LAD)
      ligation of the coronary artery followed by intramyocardial PBS injections
      (control group), and LAD ligation followed by NP12 administration (NP12 group).
      After 7 and 14 days, the extents of fibrosis and integrity of blood vessels were
      determined. Intramyocardial administration of NP12 increased phosphorylation of
      GSK-3beta, reduced fibrosis, and restored diastolic function in the mice that had
      experienced an AMI. Morphometric analyses revealed increased CD31+ and Ki67+
      vascular structures and decreased apoptosis in these mice. NP12 administration
      mediated proliferation of reparative cells in the AMI hearts. In a time-course
      analysis, Wnt3a and NP12 stabilized beta-catenin and increased expression of both
      Nanog and VEGFR2. Moreover, NP12 increased the expression of beta-catenin and
      Nanog in myocardium from AMI mice. Finally, loss- and gain-of-function
      experiments indicated that the NP12-mediated benefit is, in part, Nanog-specific.
      These findings indicate that NP12 reduces fibrosis, reestablishes coronary blood
      flow, and improves ventricular function following an AMI. We conclude that NP12
      might be useful for limiting ventricular remodeling after an AMI.

PMID- 29070681
TI  - Differential catalytic promiscuity of the alkaline phosphatase superfamily
      bimetallo core reveals mechanistic features underlying enzyme evolution.
AB  - Members of enzyme superfamilies specialize in different reactions but often
      exhibit catalytic promiscuity for one another's reactions, consistent with
      catalytic promiscuity as an important driver in the evolution of new enzymes.
      Wanting to understand how catalytic promiscuity and other factors may influence
      evolution across a superfamily, we turned to the well-studied alkaline
      phosphatase (AP) superfamily, comparing three of its members, two evolutionarily
      distinct phosphatases and a phosphodiesterase. We mutated distinguishing active
      site residues to generate enzymes that had a common Zn2+ bimetallo core but
      little sequence similarity and different auxiliary domains. We then tested the
      catalytic capabilities of these pruned enzymes with a series of substrates. A
      substantial rate enhancement of ~1011-fold for both phosphate mono- and diester
      hydrolysis by each enzyme indicated that the Zn2+ bimetallo core is an effective
      mono/di-esterase generalist and that the bimetallo cores were not evolutionarily
      tuned to prefer their cognate reactions. In contrast, our pruned enzymes were
      ineffective sulfatases, and this limited promiscuity may have provided a driving
      force for founding the distinct one-metal-ion branch that contains all known AP
      superfamily sulfatases. Finally, our pruned enzymes exhibited 107-108-fold
      phosphotriesterase rate enhancements, despite absence of such enzymes within the
      AP superfamily. We speculate that the superfamily active-site architecture
      involved in nucleophile positioning prevents accommodation of the additional
      triester substituent. Overall, we suggest that catalytic promiscuity, and the
      ease or difficulty of remodeling and building onto existing protein scaffolds,
      have greatly influenced the course of enzyme evolution. Uncovering principles and
      properties of enzyme function, promiscuity, and repurposing provides lessons for
      engineering new enzymes.

PMID- 29070682
TI  - Epistastic Interactions within the Junin Virus Envelope Glycoprotein Complex
      Provide an Evolutionary Barrier to Reversion in the Live-Attenuated Candid#1
      Vaccine.
AB  - The Candid#1 strain of Junin virus was developed using a conventional attenuation
      strategy of serial passage in nonhost animals and cultured cells. The live
      attenuated Candid#1 vaccine is used in Argentina to protect at-risk individuals
      against Argentine hemorrhagic fever, but it has not been licensed in the United
      States. Recent studies have revealed that Candid#1 attenuation is entirely
      dependent on a phenylalanine-to-isoleucine substitution at position 427 in the
      fusion subunit (GP2) of the viral envelope glycoprotein complex (GPC), thereby
      raising concerns regarding the potential for reversion to virulence. In this
      study, we report the identification and characterization of an intragenic
      epistatic interaction between the attenuating F427I mutation in GP2 and a lysine
      to-serine mutation at position 33 in the stable signal peptide (SSP) subunit of
      GPC, and we demonstrate the utility of this interaction in creating an
      evolutionary barrier against reversion to the pathogenic genotype. In the
      presence of the wild-type F427 residue, the K33S mutation abrogates the ability
      of ectopically expressed GPC to mediate membrane fusion at endosomal pH. This
      defect is rescued by the attenuating F427I mutation. We show that the recombinant
      Candid#1 (rCan) virus bearing K33S GPC is viable and retains its attenuated
      genotype under cell culture conditions that readily select for reversion in the
      parental rCan virus. If back-mutation to F427 offers an accessible pathway to
      increase fitness in rCan, reversion in K33S-GPC rCan is likely to be lethal. The
      epistatic interaction between K33S and F427I thus may minimize the likelihood of
      reversion and enhance safety in a second-generation Candid#1 vaccine.IMPORTANCE
      The live-attenuated Candid#1 vaccine strain of Junin virus is used to protect
      against Argentine hemorrhagic fever. Recent findings that a single missense
      mutation in the viral envelope glycoprotein complex (GPC) is responsible for
      attenuation raise the prospect of facile reversion to pathogenicity. Here, we
      characterize a genetic interaction between GPC subunits that evolutionarily
      forces retention of the attenuating mutation. By incorporating this secondary
      mutation into Candid#1 GPC, we hope to minimize the likelihood of reversion and
      enhance safety in a second-generation Candid#1 vaccine. A similar approach may
      guide the design of live-attenuated vaccines against Lassa and other arenaviral
      hemorrhagic fevers.

PMID- 29070683
TI  - Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1
      Infectivity.
AB  - HLA-C expression is associated with a differential ability to control HIV-1
      infection. Higher HLA-C levels may lead to better control of HIV-1 infection
      through both a higher efficiency of antigen presentation to cytotoxic T
      lymphocytes and the triggering of activating killer immunoglobulin-like receptors
      on NK cells, whereas lower levels may provide poor HIV-1 control and rapid
      progression to AIDS. We characterized the relative amounts of HLA-C heterotrimers
      (heavy chain/beta2 microglobulin [beta2m]/peptide) and HLA-C free heavy chains on
      peripheral blood mononuclear cells (PBMCs) from healthy blood donors harboring
      both alleles with stable or unstable binding to beta2m/peptide. We analyzed the
      stability of HLA-C heterotrimers of different allotypes and the infectivity of
      HIV-1 virions produced by PBMCs with various allotypes. We observed significant
      differences in HLA-C heterotrimer stability and in expression levels. We found
      that R5 HIV-1 virions produced by PBMCs harboring unstable HLA-C alleles were
      more infectious than those produced by PBMCs carrying the stable variants. We
      propose that HIV-1 infectivity might depend both on the amounts of HLA-C
      molecules and on their stability as trimeric complex. According to this model,
      individuals with low-expression HLA-C alleles and unstable binding to
      beta2m/peptide might have worse control of HIV-1 infection and an intrinsically
      higher capacity to support viral replication.IMPORTANCE Following HIV-1
      infection, some people advance rapidly to AIDS while others have slow disease
      progression. HLA-C, a molecule involved in immunity, is a key determinant of HIV
      1 control. Here we reveal how HLA-C variants contribute to the modulation of
      viral infectivity. HLA-C is present on the cell surface in two different
      conformations. The immunologically active conformation is part of a complex that
      includes beta2 microglobulin/peptide; the other conformation is not bound to
      beta2 microglobulin/peptide and can associate with HIV-1, increasing its
      infectivity. Individuals with HLA-C variants with a predominance of
      immunologically active conformations would display stronger immunity to HIV-1,
      reduced viral infectivity and effective control of HIV-1 infection, while
      subjects with HLA-C variants that easily dissociate from beta2
      microglobulin/peptide would have a reduced immunological response to HIV-1 and
      produce more infectious virions. This study provides new information that could
      be useful in the design of novel vaccine strategies and therapeutic approaches to
      HIV-1.

PMID- 29070684
TI  - NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is
      Primed To Bind and Unwind Viral RNA.
AB  - Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral
      replication and assembly (nonstructural protein 3 [NS3]). This helicase has
      become the focus of extensive basic research on the general helicase mechanism,
      and it is also of interest as a novel drug target. Despite the importance of this
      protein, mechanistic work on NS3 has been conducted almost exclusively on
      variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV
      strains that are used to study HCV genetics and mechanism in cell culture (such
      as JFH-1) is lacking. We therefore set out to determine whether NS3 from the
      replicatively efficient genotype 2a strain JFH-1 displays novel functional or
      structural properties. Using biochemical assays for RNA binding and duplex
      unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously
      studied NS3 variants from genotype 1b. Unlike NS3 variants from other genotypes,
      JFH-1 NS3 binds RNA with high affinity in a functionally active form that is
      capable of immediately unwinding RNA duplexes without undergoing rate-limiting
      conformational changes that precede activation. Unlike other superfamily 2 (SF2)
      helicases, JFH-1 NS3 does not require long 3' overhangs, and it unwinds duplexes
      that are flanked by only a few nucleotides, as in the folded HCV genome. To
      understand the physical basis for this, we solved the crystal structure of JFH-1
      NS3, revealing a novel conformation that contains an open, positively charged RNA
      binding cleft that is primed for productive interaction with RNA targets,
      potentially explaining robust replication by HCV JFH-1.IMPORTANCE Genotypes of
      HCV are as divergent as different types of flavivirus, and yet mechanistic
      features of HCV variants are presumed to be held in common. One of the most well
      studied components of the HCV replication complex is a helicase known as
      nonstructural protein 3 (NS3). We set out to determine whether this important
      mechanical component possesses biochemical and structural properties that differ
      between common strains such as those of genotype 1b and a strain of HCV that
      replicates with exceptional efficiency (JFH-1, classified as genotype 2a).
      Indeed, unlike the inefficient genotype 1b NS3, which has been well studied, JFH
      1 NS3 is a superhelicase with strong RNA affinity and high unwinding efficiency
      on a broad range of targets. Crystallographic analysis reveals architectural
      features that promote enhanced biochemical activity of JFH-1 NS3. These findings
      show that even within a single family of viruses, drift in sequence can result in
      the acquisition of radically new functional properties that enhance viral
      fitness.

PMID- 29070685
TI  - Residues 28 to 39 of the Extracellular Loop 1 of Chicken Na+/H+ Exchanger Type I
      Mediate Cell Binding and Entry of Subgroup J Avian Leukosis Virus.
AB  - Chicken Na+/H+ exchanger type I (chNHE1), a multispan transmembrane protein, is a
      cellular receptor of the subgroup J avian leukosis virus (ALV-J). To identify the
      functional determinants of chNHE1 responsible for the ALV-J receptor activity, a
      series of chimeric receptors was created by exchanging the extracellular loops
      (ECL) of human NHE1 (huNHE1) and chNHE1 and by ECL replacement with a
      hemagglutinin (HA) tag. These chimeric receptors then were used in binding and
      entry assays to map the minimal ALV-J gp85-binding domain of chNHE1. We show that
      ECL1 of chNHE1 (chECL1) is the critical functional ECL that interacts directly
      with ALV-J gp85; ECL3 is also involved in ALV-J gp85 binding. Amino acid residues
      28 to 39 of the N-terminal membrane-proximal region of chECL1 constitute the
      minimal domain required for chNHE1 binding of ALV-J gp85. These residues are
      sufficient to mediate viral entry into ALV-J nonpermissive cells. Point mutation
      analysis revealed that A30, V33, W38, and E39 of chECL1 are the key residues
      mediating the binding between chNHE1 and ALV-J gp85. Further, the replacement of
      residues 28 to 39 of huNHE1 with the corresponding chNHE1 residues converted the
      nonfunctional ALV-J receptor huNHE1 to a functional one. Importantly, soluble
      chECL1 and huECL1 harboring chNHE1 residues 28 to 39 both could effectively block
      ALV-J infection. Collectively, our findings indicate that residues 28 to 39 of
      chNHE1 constitute a domain that is critical for receptor function and mediate ALV
      J entry.IMPORTANCE chNHE1 is a cellular receptor of ALV-J, a retrovirus that
      causes infections in chickens and serious economic losses in the poultry
      industry. Until now, the domains determining the chNHE1 receptor function
      remained unknown. We demonstrate that chECL1 is critical for receptor function,
      with residues 28 to 39 constituting the minimal functional domain responsible for
      chNHE1 binding of ALV-J gp85 and efficiently mediating ALV-J cell entry. These
      residues are located in the membrane-proximal region of the N terminus of chECL1,
      suggesting that the binding site of ALV-J gp85 on chNHE1 is probably located on
      the apex of the molecule; the receptor-binding mode might be different from that
      of retroviruses. We also found that soluble chECL1, as well as huECL1 harboring
      chNHE1 residues 28 to 39, effectively blocked ALV-J infection. These findings
      contribute to a better understanding of the ALV-J infection mechanism and also
      provide new insights into the control strategies for ALV-J infection.

PMID- 29070686
TI  - Infectious Laryngotracheitis Virus Viral Chemokine-Binding Protein Glycoprotein G
      Alters Transcription of Key Inflammatory Mediators In Vitro and In Vivo.
AB  - Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that infects
      chickens, causing upper respiratory tract disease and significant losses to
      poultry industries worldwide. Glycoprotein G (gG) is a broad-range viral
      chemokine-binding protein conserved among most alphaherpesviruses, including
      ILTV. A number of studies comparing the immunological parameters between
      infection with gG-expressing and gG-deficient ILTV strains have demonstrated that
      expression of gG is associated with increased virulence, modification of the
      amount and the composition of the inflammatory response, and modulation of the
      immune responses toward antibody production and away from cell-mediated immune
      responses. The aims of the current study were to examine the establishment of
      infection and inflammation by ILTV and determine how gG influences that response
      to infection. In vitro infection studies using tracheal organ tissue specimen
      cultures and blood-derived monocytes and in vivo infection studies in specific
      pathogen-free chickens showed that leukocyte recruitment to the site of infection
      is an important component of the induced pathology and that this is influenced by
      the expression of ILTV gG and changes in the transcription of the chicken
      orthologues of mammalian CXC chemokine ligand 8 (CXCL8), chicken CXCLi1 and
      chicken CXCLi2, among other cytokines and chemokines. The results from this study
      demonstrate that ILTV gG interferes with chemokine and cytokine transcription at
      different steps of the inflammatory cascade, thus altering inflammation,
      virulence, and the balance of the immune response to infection.IMPORTANCE
      Infectious laryngotracheitis virus is an alphaherpesvirus that expresses gG, a
      conserved broad-range viral chemokine-binding protein known to interfere with
      host immune responses. However, little is known about how gG modifies virulence
      and influences the inflammatory signaling cascade associated with infection.
      Here, data from in vitro and in vivo infection studies are presented. These data
      show that gG has a direct impact on the transcription of cytokines and chemokine
      ligands in vitro (such as chicken CXCL8 orthologues, among others), which
      explains the altered balance of the inflammatory response that is associated with
      gG during ILTV infection of the upper respiratory tract of chickens. This is the
      first report to associate gG with the dysregulation of cytokine transcription at
      different stages of the inflammatory cascade triggered by ILTV infection of the
      natural host.

PMID- 29070687
TI  - Rotavirus degrades multiple type interferon receptors to inhibit IFN signaling
      and protects against mortality from endotoxin in suckling mice.
AB  - STAT1 phosphorylation in response to exogenous IFN administration can be
      inhibited by rotaviral replication both in vitro and in vivo. In addition many
      rotavirus strains are resistant to the actions of different IFN types . The
      regulation of multiple IFN type-mediated antiviral pathways by RVs is not well
      understood. In this study, we find that during infection in vitro and in vivo RV
      significantly depletes IFN-type I, II, and III receptors (IFNRs). Regulation of
      IFNRs occurred exclusively within RV-infected cells and could be abrogated by
      inhibiting the lysosomal-endosomal degradation pathway. In vitro, IFNR
      degradation was conserved across multiple RV strains that differ in their modes
      of regulating IFN induction. In suckling mice, exogenously administered types I,
      II, or III IFN each induced phosphorylation of STAT1-Y701 within intestinal
      epithelial cells (IECs) of suckling mice. Murine EW strain RV infection
      transiently activated intestinal STAT1 at 1dpi, but not subsequently at 2-3dpi.
      In response to injection of purified IFN-alpha/beta or -lambda, IECs in EW
      infected mice exhibited impaired STAT1-Y701 phosphorylation, correlating with
      depletion of different intestinal IFNRs and impaired IFN-mediated transcription.
      The ability of EW murine RV to inhibit multiple IFN types led us to test
      protection of suckling mice from endotoxin-mediated shock, an outcome that is
      dependent on the host IFN response. Compared to controls, mice infected with EW
      murine RV were substantially protected against mortality following parenteral
      endotoxin administration. These studies identify a novel mechanism of IFN
      subversion by RV and reveal an unexpected protective effect of RV infection on
      endotoxin-mediated shock in suckling mice.IMPORTANCE Antiviral functions of types
      1, 2, and 3 IFN are mediated by receptor-dependent activation of STAT1. Here we
      find that RV degrades the types 1, 2, and 3 IFN receptors (IFNR) in vitro In a
      suckling mouse model, RV effectively blocked STAT1 activation and transcription
      following injection of different purified IFNs. This correlated with
      significantly decreased protein expression of intestinal types 1 and 2 IFNRs.
      Recent studies demonstrate that in mice, LPS-induced lethality is prevented by
      genetic ablation of IFN signaling genes such as IFNAR1 and STAT1. When suckling
      mice were infected with RV they were substantially protected from lethal exposure
      to endotoxin. These findings provide novel insights into the mechanisms
      underlying rotavirus regulation of different interferons and are likely to
      stimulate new research into both rotavirus pathogenesis and endotoxemia.

PMID- 29070688
TI  - Structural Basis for Escape of Human Astrovirus from Antibody Neutralization:
      Broad Implications for Rational Vaccine Design.
AB  - Human astroviruses are recognized as a leading cause of viral diarrhea worldwide
      in children, immunocompromised patients, and the elderly. There are currently no
      vaccines available to prevent astrovirus infection; however, antibodies developed
      by healthy individuals during previous infection correlate with protection from
      reinfection, suggesting that an effective vaccine could be developed. In this
      study, we investigated the molecular mechanism by which several strains of human
      astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing
      monoclonal antibody PL-2 (MAb PL-2). Sequencing of the HAstV-2 capsid genes
      reveals mutations in the PL-2 epitope within the capsid's spike domain. To
      understand the molecular basis for resistance from MAb PL-2 neutralization, we
      determined the 1.35-A-resolution crystal structure of the capsid spike from one
      of these HAstV-2 strains. Our structure reveals a dramatic conformational change
      in a loop within the PL-2 epitope due to a serine-to-proline mutation, locking
      the loop in a conformation that sterically blocks binding and neutralization by
      MAb PL-2. We show that mutation to serine permits loop flexibility and recovers
      MAb PL-2 binding. Importantly, we find that HAstV-2 capsid spike containing a
      serine in this loop is immunogenic and elicits antibodies that neutralize all
      HAstV-2 strains. Taken together, our results have broad implications for rational
      selection of vaccine strains that do not contain prolines in antigenic loops, so
      as to elicit antibodies against diverse loop conformations.IMPORTANCE Human
      astroviruses (HAstVs) infect nearly every person in the world during childhood
      and cause diarrhea, vomiting, and fever. In this study, we investigated how
      several strains of HAstV are resistant to a virus-neutralizing monoclonal
      antibody. We determined the crystal structure of the capsid protein spike domain
      from one of these HAstV strains and found that a single amino acid mutation
      induces a structural change in a loop that is responsible for antibody binding.
      Our findings reveal how viruses can escape antibody neutralization and provide
      insight for the rational design of vaccines to elicit diverse antibodies that
      provide broader protection from infection.

PMID- 29070689
TI  - Both sphingomyelin and cholesterol in the host cell membrane are essential for
      Rubella virus entry.
AB  - Rubella virus (RuV) causes a systemic infection and transplacental fetal
      infection causes congenital rubella syndrome. In this study, we showed that
      treatment of cells with sphingomyelinase inhibited RuV infection. Assays using
      inhibitors of serine palmitoyl transferase and ceramide transport protein
      demonstrated the contribution of sphingomyelin (SM) to RuV infection. Compelling
      evidence for direct binding of RuV to lipid membranes at neutral pH was obtained
      using liposome co-flotation assays. The absence of either SM or cholesterol
      (Chol) abrogated the RuV--liposome interaction. SM and Chol (SM/Chol) were also
      critical for RuV binding to erythrocytes and lymphoid cells. Removal of Ca2+ from
      the assay buffer or mutation of RuV envelope E1 protein Ca2+-binding sites
      abrogated RuV binding to liposomes, erythrocytes, and lymphoid cells. However,
      RuV bound to various non-lymphoid adherent cell lines independently of
      extracellular Ca2+ or SM/Chol. Even in these adherent cell lines, both the E1
      protein Ca2+-binding sites and cellular SM/Chol were essential for the early
      stage of RuV infection, possibly affecting envelope-membrane fusion in acidic
      compartments. Myelin oligodendrocyte glycoprotein (MOG) has recently been
      identified as a cellular receptor for RuV. However, RuV bound to MOG-negative
      cells in a Ca2+-independent manner. Collectively, our data demonstrate that RuV
      has two distinct binding mechanisms: one is Ca2+-dependent and the other Ca2+
      independent. Ca2+-dependent binding observed in lymphoid cells occurs by the
      direct interaction between E1 protein fusion loops and SM/Chol-enriched
      membranes. Clarification of the mechanism of Ca2+-independent RuV binding is an
      important next step in understanding the pathology of RuV infection.IMPORTANCE
      Rubella has a significant impact on public health as infection during early
      pregnancy can result in babies being born with congenital rubella syndrome.
      Despite effective rubella vaccines being available, rubella outbreaks still occur
      in many countries. We studied the entry mechanism of Rubella virus (RuV) and
      found that RuV binds directly to the host plasma membrane in the presence of Ca2+
      at neutral pH. This Ca2+-dependent binding is specifically directed to membranes
      enriched in sphingomyelin and cholesterol, and is critical for RuV infection.
      Importantly, RuV also binds to many cell lines in a Ca2+-independent manner. An
      unidentified RuV receptor(s) is involved in this Ca2+-independent binding. We
      believe that the data presented here may aid the development of the first anti
      RuV drug.

PMID- 29070690
TI  - Genotype 2 strains of porcine reproductive and respiratory syndrome virus
      dysregulate alveolar macrophage cytokine production via the unfolded protein
      response.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) infects alveolar
      macrophages (AMPhi) causing dysregulated interferon (IFN)-alpha and tumor
      necrosis factor (TNF)-alpha production through a mechanism(s) yet to be resolved.
      Here, we show that AMPhi infected with PRRSV secreted a reduced quantity of IFN
      alpha following the cell exposure to synthetic dsRNA. This reduction did not
      correlate with reduced IFNA1 gene transcription. Rather, it coincided with two
      events that occurred late during infection and were indicative of translational
      attenuation, specifically, the activation of eukaryotic translation initiation
      factor 2alpha (eIF2alpha), and the appearance of stress granules. Notably, the
      typical rapid production of TNF-alpha by AMPhi exposed to lipopolysaccharide
      (LPS) was suppressed or enhanced by PRRSV depending on when the LPS exposure
      occurred after virus infection. If exposure was delayed until 6 h post-infection
      (hpi) so that the development of the cytokine response coincided with the time in
      which phosphorylation of eIF2alpha by the stress sensor PERK (protein kinase RNA
      (PKR)-like ER kinase) occurred, inhibition of TNF-alpha production was observed.
      However, if LPS exposure occurred at 2 hpi, prior to a detectable onset of
      eIF2alpha phosphorylation, a synergistic response was observed due to the earlier
      NF-kappaB activation via the stress sensor IRE1alpha (inositol-requiring kinase
      1alpha). These results suggest that the asynchronous actions of two branches of
      the unfolded protein response (UPR), namely IRE1alpha, and PERK, activated by ER
      stress resulting from the virus infection, are associated with enhancement or
      suppression of TNF-alpha production, respectively.IMPORTANCE The activation of
      AMPhi is controlled by its microenvironment to deter excessive pro-inflammatory
      cytokine responses to microbes that could impair lung function. However, viral
      pneumonias frequently become complicated by secondary bacterial infections
      triggering severe inflammation, lung dysfunction, and death. Although
      dysregulated cytokine production is considered an integral component of the
      exacerbated inflammatory response in viral-bacterial co-infections, the mechanism
      responsible for this event is unknown. Here, we show that PRRSV replication in
      porcine AMPhi triggers activation of the IRE1alpha branch of the UPR, which
      causes a synergistic TNF-alpha response to LPS exposure. Thus, the severe
      pneumonias typically observed in pigs afflicted with PRRSV-bacterial co
      infections could result from dysregulated, overly robust TNF-alpha production to
      opportunistic pathogens that is not commensurate with the typical restrained
      reaction by uninfected AMPhi. This notion could help design therapies to mitigate
      the severity of viral and bacterial co-infections.

PMID- 29070691
TI  - Structure, Immunogenicity, and Protective Mechanism of an Engineered Enterovirus
      71-Like Particle Vaccine Mimicking 80S Empty Capsid.
AB  - Enterovirus 71 (EV71) is the major causative agent of severe hand, foot, and
      mouth disease, which affects millions of young children in the Asia-Pacific
      region annually. In this study, we engineered a novel EV71 virus-like particle
      (VLP) that lacks VP4 (therefore designated VLPDeltaVP4) and investigated its
      structure, antigenicity, and vaccine potential. The cryo-electron microscopy
      (cryo-EM) structure of VLPDeltaVP4 was reconstructed to 3.71-A resolution.
      Results from structural and biochemical analyses revealed that VLPDeltaVP4
      resembles the end product of the viral uncoating process, the 80S empty capsid.
      VLPDeltaVP4 is able to elicit high-titer neutralizing antibodies and to fully
      protect mice against lethal viral challenge. Mechanistic studies showed that, at
      the cellular level, the anti-VLPDeltaVP4 sera exert neutralization effects at
      both pre- and postattachment stages by inhibiting both virus attachment and
      internalization, and at the molecular level, the antisera can block multiple
      interactions between EV71 and its key receptors. Our study gives a better
      understanding of EV71 capsid assembly and provides important information for the
      design and development of new-generation vaccines for EV71, and perhaps for other
      enteroviruses, as well.IMPORTANCE Enterovirus 71 (EV71) infection may lead to
      severe hand, foot, and mouth disease, with significant morbidity and mortality.
      Knowledge regarding EV71 particle assembly remains limited. Here, we report the
      generation and characterization of a novel EV71 virus-like particle that lacks
      the VP4 capsid subunit protein. This particle, termed VLPDeltaVP4, structurally
      mimics the 80S empty capsid, which is the end stage of EV71 uncoating. We further
      show that VLPDeltaVP4 exhibits desirable immunogenicity and protective efficacy
      in proof-of-concept studies. In addition, the inhibitory mechanisms of the
      VLPDeltaVP4-induced antibodies are unraveled at both the cellular and molecular
      levels. Our work provides the first evidence of picornaviral particle assembly in
      the complete absence of VP4 and identifies VLPDeltaVP4 as an improved EV71
      vaccine candidate with desirable traits. These findings not only enhance our
      understanding of particle assembly and uncoating of picornaviruses, but also
      provide important information for structure-guided vaccine design for EV71 and
      other enteroviruses.

PMID- 29070692
TI  - The Postfusion Structure of the Heartland Virus Gc Glycoprotein Supports
      Taxonomic Separation of the Bunyaviral Families Phenuiviridae and Hantaviridae.
AB  - Heartland virus (HRTV) is an emerging human pathogen that belongs to the newly
      defined family Phenuiviridae, order Bunyavirales Gn and Gc are two viral surface
      glycoproteins encoded by the M segment and are required for early events during
      infection. HRTV delivers its genome into the cytoplasm by fusion of the viral
      envelope and endosomal membranes under low-pH conditions. Here, we describe the
      crystal structure of HRTV Gc in its postfusion conformation. The structure shows
      that Gc displays a typical class II fusion protein conformation, and the overall
      structure is identical to severe fever with thrombocytopenia syndrome virus
      (SFTSV) Gc, which also belongs to the Phenuiviridae family. However, our
      structural analysis indicates that the hantavirus Gc presents distinct features
      in the aspects of subdomain orientation, N-linked glycosylation, the interaction
      pattern between protomers, and the fusion loop conformation. This suggests their
      family-specific subunit arrangement during the fusogenic process and supports the
      recent taxonomic revision of bunyaviruses. Our results provide insights into the
      comprehensive comparison of class II membrane fusion proteins in two bunyavirus
      families, yielding valuable information for treatments against these human
      pathogens.IMPORTANCE HRTV is an insect-borne virus found in America that can
      infect humans. It belongs to the newly defined family Phenuiviridae, order
      Bunyavirales HRTV contains three single-stranded RNA segments (L, M, and S). The
      M segment of the virus encodes a polyprotein precursor that is cleaved into two
      glycoproteins, Gn and Gc. Gc is a fusion protein facilitating virus entry into
      host cells. Here, we report the crystal structure of the HRTV Gc protein. The
      structure displays a typical class II fusion protein conformation. Comparison of
      HRTV Gc with a recently solved structure of another bunyavirus Gc revealed that
      these Gc structures display a newly defined family specificity, supporting the
      recent International Committee on Taxonomy of Viruses reclassification of the
      bunyaviruses. Our results expand the knowledge of bunyavirus fusion proteins and
      help us to understand bunyavirus characterizations. This study provides useful
      information to improve protection against and therapies for bunyavirus
      infections.

PMID- 29070693
TI  - Cryo-Electron Microscopy Structure of Porcine Deltacoronavirus Spike Protein in
      the Prefusion State
AB  - Coronavirus spike proteins from different genera are divergent, although they all
      mediate coronavirus entry into cells by binding to host receptors and fusing
      viral and cell membranes. Here, we determined the cryo-electron microscopy
      structure of porcine deltacoronavirus (PdCoV) spike protein at 3.3-A resolution.
      The trimeric protein contains three receptor-binding S1 subunits that tightly
      pack into a crown-like structure and three membrane fusion S2 subunits that form
      a stalk. Each S1 subunit contains two domains, an N-terminal domain (S1-NTD) and
      C-terminal domain (S1-CTD). PdCoV S1-NTD has the same structural fold as alpha-
      and betacoronavirus S1-NTDs as well as host galectins, and it recognizes sugar as
      its potential receptor. PdCoV S1-CTD has the same structural fold as
      alphacoronavirus S1-CTDs, but its structure differs from that of betacoronavirus
      S1-CTDs. PdCoV S1-CTD binds to an unidentified receptor on host cell surfaces.
      PdCoV S2 is locked in the prefusion conformation by structural restraint of S1
      from a different monomeric subunit. PdCoV spike possesses several structural
      features that may facilitate immune evasion by the virus, such as its compact
      structure, concealed receptor-binding sites, and shielded critical epitopes.
      Overall, this study reveals that deltacoronavirus spikes are structurally and
      evolutionally more closely related to alphacoronavirus spikes than to
      betacoronavirus spikes; it also has implications for the receptor recognition,
      membrane fusion, and immune evasion by deltacoronaviruses as well as
      coronaviruses in general.IMPORTANCEIn this study, we determined the cryo-electron
      microscopy structure of porcine deltacoronavirus (PdCoV) spike protein at a 3.3-A
      resolution. This is the first atomic structure of a spike protein from the
      deltacoronavirus genus, which is divergent in amino acid sequences from the well
      studied alpha- and betacoronavirus spike proteins. Here, we described the overall
      structure of the PdCoV spike and the detailed structure of each of its structural
      elements. Moreover, we analyzed the functions of each of the structural elements.
      Based on the structures and functions of these structural elements, we discussed
      the evolution of PdCoV spike protein in relation to the spike proteins from other
      coronavirus genera. This study combines the structure, function, and evolution of
      PdCoV spike protein and provides many insights into its receptor recognition,
      membrane fusion, and immune evasion.

PMID- 29070695
TI  - Relationship between DNA Methylation in the 5' CpG Island of the SLC47A1
      (Multidrug and Toxin Extrusion Protein MATE1) Gene and Interindividual
      Variability in MATE1 Expression in the Human Liver.
AB  - Multidrug and toxin extrusion protein 1 (MATE1), which is encoded by solute
      carrier 47A1 (SLC47A1), mediates the excretion of organic cations into bile and
      urine. Some genetic variants in human MATE1 altered its transport function in in
      vitro experiments; however, differences in the pharmacokinetics of substrate
      drugs cannot be explained by genetic variations in humans. In this study, we
      investigated whether DNA methylation was involved in interindividual variability
      in MATE1 expression in the human liver. Approximately 20-fold interindividual
      variability in MATE1 mRNA expression levels was observed in liver samples and
      mRNA expression levels negatively correlated with methylation levels of the CpG
      island in the 27 kb upstream of SLC47A1 DNA demethylation by treatment with 5-aza
      2'-deoxycytidine increased MATE1 mRNA expression in MATE1-negative cell lines.
      The luciferase reporter assay showed that the CpG island increased the
      transcriptional activity of the SLC47A1 promoter. MATE1 mRNA expression levels
      were significantly lower in CpG island knockout HepG2 cells than in control
      cells. These results suggest that the 5' CpG island of SLC47A1 acts as an
      enhancer for SLC47A1, and DNA methylation in the CpG island plays an important
      role in interindividual differences in hepatic MATE1 expression.

PMID- 29070694
TI  - Emergence and Adaptation of a Novel Highly Pathogenic H7N9 Influenza Virus in
      Birds and Humans from a 2013 Human-Infecting Low-Pathogenic Ancestor.
AB  - Since its emergence in 2013, the H7N9 low-pathogenic avian influenza virus
      (LPAIV) has been circulating in domestic poultry in China, causing five waves of
      human infections. A novel H7N9 highly pathogenic avian influenza virus (HPAIV)
      variant possessing multiple basic amino acids at the cleavage site of the
      hemagglutinin (HA) protein was first reported in two cases of human infection in
      January 2017. More seriously, those novel H7N9 HPAIV variants have been
      transmitted and caused outbreaks on poultry farms in eight provinces in China.
      Herein, we demonstrate the presence of three different amino acid motifs at the
      cleavage sites of these HPAIV variants which were isolated from chickens and
      humans and likely evolved from the preexisting LPAIVs. Animal experiments showed
      that these novel H7N9 HPAIV variants are both highly pathogenic in chickens and
      lethal to mice. Notably, human-origin viruses were more pathogenic in mice than
      avian viruses, and the mutations in the PB2 gene associated with adaptation to
      mammals (E627K, A588V, and D701N) were identified by next-generation sequencing
      (NGS) and Sanger sequencing of the isolates from infected mice. No polymorphisms
      in the key amino acid substitutions of PB2 and HA in isolates from infected
      chicken lungs were detected by NGS. In sum, these results highlight the high
      degree of pathogenicity and the valid transmissibility of this new H7N9 variant
      in chickens and the quick adaptation of this new H7N9 variant to mammals, so the
      risk should be evaluated and more attention should be paid to this
      variant.IMPORTANCE Due to the recent increased numbers of zoonotic infections in
      poultry and persistent human infections in China, influenza A(H7N9) virus has
      remained a public health threat. Most of the influenza A(H7N9) viruses reported
      previously have been of low pathogenicity. Now, these novel H7N9 HPAIV variants
      have caused human infections in three provinces and outbreaks on poultry farms in
      eight provinces in China. We analyzed the molecular features and compared the
      relative characteristics of one H7N9 LPAIV and two H7N9 HPAIVs isolated from
      chickens and two human-origin H7N9 HPAIVs in chicken and mouse models. We found
      that all HPAIVs both are highly pathogenic and have valid transmissibility in
      chickens. Strikingly, the human-origin viruses were more highly pathogenic than
      the avian-origin viruses in mice, and dynamic mutations were confirmed by NGS and
      Sanger sequencing. Our findings offer important insight into the origin,
      adaptation, pathogenicity, and transmissibility of these viruses to both poultry
      and mammals.

PMID- 29070697
TI  - Overcoming mutational complexity in acute myeloid leukemia by inhibition of
      critical pathways.
AB  - Numerous variant alleles are associated with human acute myeloid leukemia (AML).
      However, the same variants are also found in individuals with no hematological
      disease, making their functional relevance obscure. Through NOD.Cg
      PrkdcscidIl2rgtmlWjl/Sz (NSG) xenotransplantation, we functionally identified
      preleukemic and leukemic stem cell populations present in FMS-like tyrosine
      kinase 3 internal tandem duplication-positive (FLT3-ITD)+ AML patient samples. By
      single-cell DNA sequencing, we identified clonal structures and linked mutations
      with in vivo fates, distinguishing mutations permissive of nonmalignant
      multilineage hematopoiesis from leukemogenic mutations. Although multiple somatic
      mutations coexisted at the single-cell level, inhibition of the mutation strongly
      associated with preleukemic to leukemic stem cell transition eliminated AML in
      vivo. Moreover, concurrent inhibition of BCL-2 (B cell lymphoma 2) uncovered a
      critical dependence of resistant AML cells on antiapoptotic pathways. Co
      inhibition of pathways critical for oncogenesis and survival may be an effective
      strategy that overcomes genetic diversity in human malignancies. This approach
      incorporating single-cell genomics with the NSG patient-derived xenograft model
      may serve as a broadly applicable resource for precision target identification
      and drug discovery.

PMID- 29070696
TI  - Structural Determinants Influencing the Potency and Selectivity of Indazole
      Paroxetine Hybrid G Protein-Coupled Receptor Kinase 2 Inhibitors.
AB  - G protein-coupled receptor kinases (GRKs) phosphorylate activated receptors to
      promote arrestin binding, decoupling from heterotrimeric G proteins, and
      internalization. GRK2 and GRK5 are overexpressed in the failing heart and thus
      have become therapeutic targets. Previously, we discovered two classes of GRK2
      selective inhibitors, one stemming from GSK180736A, a Rho-associated coiled-coil
      containing kinase 1 (ROCK1) inhibitor, the other from paroxetine, a selective
      serotonin-reuptake inhibitor. These two classes of compounds bind to the GRK2
      active site in a similar configuration but contain different hinge-binding
      "warheads": indazole and benzodioxole, respectively. We surmised from our prior
      studies that an indazole would be the stronger hinge binder and would impart
      increased potency when substituted for benzodioxole in paroxetine derivatives. To
      test this hypothesis, we synthesized a series of hybrid compounds that allowed us
      to compare the effects of inhibitors that differ only in the identity of the
      warhead. The indazole-paroxetine analogs were indeed more potent than their
      respective benzodioxole derivatives but lost selectivity. To investigate how
      these two warheads dictate selectivity, we determined the crystal structures of
      three of the indazole hybrid compounds (CCG224061, CCG257284, and CCG258748) in
      complex with GRK2-Gbetagamma Comparison of these structures with those of
      analogous benzodioxole-containing complexes confirmed that the indazole
      paroxetine hybrids form stronger interactions with the hinge of the kinase but
      also stabilize a distinct conformation of the kinase domain of GRK2 compared with
      previous complexes with paroxetine analogs. This conformation is analogous to one
      that can be assumed by GRK5, at least partially explaining the loss in
      selectivity.

PMID- 29070698
TI  - Transplantation of wild-type mouse hematopoietic stem and progenitor cells
      ameliorates deficits in a mouse model of Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) is an incurable autosomal recessive neurodegenerative
      disease caused by reduced expression of the mitochondrial protein frataxin due to
      an intronic GAA-repeat expansion in the FXN gene. We report the therapeutic
      efficacy of transplanting wild-type mouse hematopoietic stem and progenitor cells
      (HSPCs) into the YG8R mouse model of FRDA. In the HSPC-transplanted YG8R mice,
      development of muscle weakness and locomotor deficits was abrogated as was
      degeneration of large sensory neurons in the dorsal root ganglia (DRGs) and
      mitochondrial capacity was improved in brain, skeletal muscle, and heart.
      Transplanted HSPCs engrafted and then differentiated into microglia in the brain
      and spinal cord and into macrophages in the DRGs, heart, and muscle of YG8R FRDA
      mice. We observed the transfer of wild-type frataxin and Cox8 mitochondrial
      proteins from HSPC-derived microglia/macrophages to FRDA mouse neurons and muscle
      myocytes in vivo. Our results show the HSPC-mediated phenotypic rescue of FRDA in
      YG8R mice and suggest that this approach should be investigated further as a
      strategy for treating FRDA.

PMID- 29070699
TI  - Inhibition of pyruvate dehydrogenase kinase improves pulmonary arterial
      hypertension in genetically susceptible patients.
AB  - Pulmonary arterial hypertension (PAH) is a progressive vascular disease with a
      high mortality rate. It is characterized by an occlusive vascular remodeling due
      to a pro-proliferative and antiapoptotic environment in the wall of resistance
      pulmonary arteries (PAs). Proliferating cells exhibit a cancer-like metabolic
      switch where mitochondrial glucose oxidation is suppressed, whereas glycolysis is
      up-regulated as the major source of adenosine triphosphate production. This
      multifactorial mitochondrial suppression leads to inhibition of apoptosis and
      downstream signaling promoting proliferation. We report an increase in pyruvate
      dehydrogenase kinase (PDK), an inhibitor of the mitochondrial enzyme pyruvate
      dehydrogenase (PDH, the gatekeeping enzyme of glucose oxidation) in the PAs of
      human PAH compared to healthy lungs. Treatment of explanted human PAH lungs with
      the PDK inhibitor dichloroacetate (DCA) ex vivo activated PDH and increased
      mitochondrial respiration. In a 4-month, open-label study, DCA (3 to 6.25 mg/kg
      b.i.d.) administered to patients with idiopathic PAH (iPAH) already on approved
      iPAH therapies led to reduction in mean PA pressure and pulmonary vascular
      resistance and improvement in functional capacity, but with a range of individual
      responses. Lack of ex vivo and clinical response was associated with the presence
      of functional variants of SIRT3 and UCP2 that predict reduced protein function.
      Impaired function of these proteins causes PDK-independent mitochondrial
      suppression and pulmonary hypertension in mice. This first-in-human trial of a
      mitochondria-targeting drug in iPAH demonstrates that PDK is a druggable target
      and offers hemodynamic improvement in genetically susceptible patients, paving
      the way for novel precision medicine approaches in this disease.

PMID- 29070700
TI  - Evolution-informed forecasting of seasonal influenza A (H3N2).
AB  - Interpandemic or seasonal influenza A, currently subtypes H3N2 and H1N1, exacts
      an enormous annual burden both in terms of human health and economic impact.
      Incidence prediction ahead of season remains a challenge largely because of the
      virus' antigenic evolution. We propose a forecasting approach that incorporates
      evolutionary change into a mechanistic epidemiological model. The proposed models
      are simple enough that their parameters can be estimated from retrospective
      surveillance data. These models link amino acid sequences of hemagglutinin
      epitopes with a transmission model for seasonal H3N2 influenza, also informed by
      H1N1 levels. With a monthly time series of H3N2 incidence in the United States
      for more than 10 years, we demonstrate the feasibility of skillful prediction for
      total cases ahead of season, with a tendency to underpredict monthly peak
      epidemic size, and an accurate real-time forecast for the 2016/2017 influenza
      season.

PMID- 29070701
TI  - Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns
      in hospitals and the community.
AB  - Genome sequencing has provided snapshots of the transmission of methicillin
      resistant Staphylococcus aureus (MRSA) during suspected outbreaks in isolated
      hospital wards. Scale-up to populations is now required to establish the full
      potential of this technology for surveillance. We prospectively identified all
      individuals over a 12-month period who had at least one MRSA-positive sample
      processed by a routine diagnostic microbiology laboratory in the East of England,
      which received samples from three hospitals and 75 general practitioner (GP)
      practices. We sequenced at least 1 MRSA isolate from 1465 individuals (2282 MRSA
      isolates) and recorded epidemiological data. An integrated epidemiological and
      phylogenetic analysis revealed 173 transmission clusters containing between 2 and
      44 cases and involving 598 people (40.8%). Of these, 118 clusters (371 people)
      involved hospital contacts alone, 27 clusters (72 people) involved community
      contacts alone, and 28 clusters (157 people) had both types of contact. Community
      and hospital-associated MRSA lineages were equally capable of transmission in
      the community, with instances of spread in households, long-term care facilities,
      and GP practices. Our study provides a comprehensive picture of MRSA transmission
      in a sampled population of 1465 people and suggests the need to review existing
      infection control policy and practice.

PMID- 29070702
TI  - Optimization of Experimental Parameters in Data-Independent Mass Spectrometry
      Significantly Increases Depth and Reproducibility of Results.
AB  - Comprehensive, reproducible and precise analysis of large sample cohorts is one
      of the key objectives of quantitative proteomics. Here, we present an
      implementation of data-independent acquisition using its parallel acquisition
      nature that surpasses the limitation of serial MS2 acquisition of data-dependent
      acquisition on a quadrupole ultra-high field Orbitrap mass spectrometer. In deep
      single shot data-independent acquisition, we identified and quantified 6,383
      proteins in human cell lines using 2-or-more peptides/protein and over 7100
      proteins when including the 717 proteins that were identified on the basis of a
      single peptide sequence. 7739 proteins were identified in mouse tissues using 2
      or-more peptides/protein and 8121 when including the 382 proteins that were
      identified based on a single peptide sequence. Missing values for proteins were
      within 0.3 to 2.1% and median coefficients of variation of 4.7 to 6.2% among
      technical triplicates. In very complex mixtures, we could quantify 10,780
      proteins and 12,192 proteins when including the 1412 proteins that were
      identified based on a single peptide sequence. Using this optimized DIA, we
      investigated large-protein networks before and after the critical period for
      whisker experience-induced synaptic strength in the murine somatosensory cortex 1
      barrel field. This work shows that parallel mass spectrometry enables proteome
      profiling for discovery with high coverage, reproducibility, precision and
      scalability.

PMID- 29070705
TI  - How to hold an ethical pox party.
AB  - Pox parties are a controversial alternative to vaccination for diseases such as
      chickenpox. Such parties involve parents infecting non-immune children by
      exposing them to a contagious child. If successful, infection will usually lead
      to immunity, thus preventing infection later in life, which, for several vaccine
      preventable diseases, is more severe than childhood infection. Some may consider
      pox parties more morally objectionable than opting out of vaccination through non
      medical exemptions. In this paper, I argue that this is not the case. Pox parties
      involve immediate risk of harm for children and reduce future harms, whereas
      opting out of vaccination places children at long-term risk of harms that
      increase with time, at least for some pathogens. Regarding harm to others through
      onward transmission of infection, this can be easily prevented in the case of pox
      parties-given the relatively controlled timing of infection-by quarantining
      attendees after the party, whereas opting out of vaccination involves risks to
      others that are more difficult to control. I defend three criteria for an ethical
      pox party: (1) that the disease is sufficiently low risk, (2) that parents
      consent to their child's attendance and (3) that children exposed to infection
      are quarantined and isolated appropriately. I argue that, if these criteria are
      met, pox parties are morally preferable to non-vaccination; such parties involve
      less risk to non-consenting others and, for some pathogens in some cases, even
      involve less risk for the children who participate. Thus, policies that permit
      non-medical exemption to vaccination should also permit ethical pox parties.
      Alternatively, if pox parties are not permitted, then vaccination should be
      mandated for those without medical contraindication.

PMID- 29070703
TI  - RNA editing with CRISPR-Cas13.
AB  - Nucleic acid editing holds promise for treating genetic disease, particularly at
      the RNA level, where disease-relevant sequences can be rescued to yield
      functional protein products. Type VI CRISPR-Cas systems contain the programmable
      single-effector RNA-guided ribonuclease Cas13. We profiled type VI systems in
      order to engineer a Cas13 ortholog capable of robust knockdown and demonstrated
      RNA editing by using catalytically inactive Cas13 (dCas13) to direct adenosine-to
      inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to
      transcripts in mammalian cells. This system, referred to as RNA Editing for
      Programmable A to I Replacement (REPAIR), which has no strict sequence
      constraints, can be used to edit full-length transcripts containing pathogenic
      mutations. We further engineered this system to create a high-specificity variant
      and minimized the system to facilitate viral delivery. REPAIR presents a
      promising RNA-editing platform with broad applicability for research,
      therapeutics, and biotechnology.

PMID- 29070706
TI  - Does egg donation for mitochondrial replacement techniques generate parental
      responsibilities?
AB  - Children created through mitochondrial replacement techniques (MRTs) are commonly
      presented as possessing 50% of their mother's nuclear DNA, 50% of their father's
      nuclear DNA and the mitochondrial DNA of an egg donor. This lab-engineered
      genetic composition has prompted two questions: Do children who are the product
      of an MRT procedure have three genetic parents? And, do MRT egg donors have
      parental responsibilities for the children created? In this paper, I address the
      second question and in doing so I also address the first one. First, I present a
      brief account of mitochondrial diseases and MRTs. Second, I examine how MRTs
      affect the numerical identity of eggs and zygotes. Third, I investigate two
      genetic accounts of parenthood and MRT egg donation. Fourth, I explore three
      causal accounts of parenthood and MRT egg donation. My conclusion is that, under
      the appropriate circumstances, MRT egg donors are parentally responsible for the
      children created under genetic accounts of parenthood and under causal accounts
      of parenthood.

PMID- 29070704
TI  - Bivalent complexes of PRC1 with orthologs of BRD4 and MOZ/MORF target
      developmental genes in Drosophila.
AB  - Regulatory decisions in Drosophila require Polycomb group (PcG) proteins to
      maintain the silent state and Trithorax group (TrxG) proteins to oppose
      silencing. Since PcG and TrxG are ubiquitous and lack apparent sequence
      specificity, a long-standing model is that targeting occurs via protein
      interactions; for instance, between repressors and PcG proteins. Instead, we
      found that Pc-repressive complex 1 (PRC1) purifies with coactivators Fs(1)h
      [female sterile (1) homeotic] and Enok/Br140 during embryogenesis. Fs(1)h is a
      TrxG member and the ortholog of BRD4, a bromodomain protein that binds to
      acetylated histones and is a key transcriptional coactivator in mammals. Enok and
      Br140, another bromodomain protein, are orthologous to subunits of a mammalian
      MOZ/MORF acetyltransferase complex. Here we confirm PRC1-Br140 and PRC1-Fs(1)h
      interactions and identify their genomic binding sites. PRC1-Br140 bind
      developmental genes in fly embryos, with analogous co-occupancy of PRC1 and a
      Br140 ortholog, BRD1, at bivalent loci in human embryonic stem (ES) cells. We
      propose that identification of PRC1-Br140 "bivalent complexes" in fly embryos
      supports and extends the bivalency model posited in mammalian cells, in which the
      coexistence of H3K4me3 and H3K27me3 at developmental promoters represents a
      poised transcriptional state. We further speculate that local competition between
      acetylation and deacetylation may play a critical role in the resolution of
      bivalent protein complexes during development.

PMID- 29070707
TI  - Adverse consequences of article 12 of the UN Convention on the Rights of Persons
      with Disabilities for persons with mental disabilities and an alternative way
      forward.
AB  - It is widely accepted among medical ethicists that competence is a necessary
      condition for informed consent. In this view, if a patient is incompetent to make
      a particular treatment decision, the decision must be based on an advance
      directive or made by a substitute decision-maker on behalf of the patient. We
      call this the competence model. According to a recent report of the United
      Nations (UN) High Commissioner for Human Rights, article 12 of the UN Convention
      on the Rights of Persons with Disabilities (CRPD) presents a wholesale rejection
      of the competence model. The High Commissioner here adopts the interpretation of
      article 12 proposed by the Committee on the Rights of Persons with Disabilities.
      On this interpretation, CRPD article 12 renders it impermissible to deny persons
      with mental disabilities the right to make treatment decisions on the basis of
      impaired decision-making capacity and demands the replacement of all regimes of
      substitute decision-making by supported decision-making. In this paper, we
      explicate six adverse consequences of CRPD article 12 for persons with mental
      disabilities and propose an alternative way forward. The proposed model combines
      the strengths of the competence model and supported decision-making.

PMID- 29070708
TI  - Vitamin A Status in Children: Mathematical Modeling Provides New Progress on an
      Old Problem.

PMID- 29070709
TI  - Increased Protein Consumption during the Day from an Energy-Restricted Diet
      Augments Satiety but Does Not Reduce Daily Fat or Carbohydrate Intake on a Free
      Living Test Day in Overweight Women.
AB  - Background: Higher-protein (HP) energy-restriction diets improve weight
      management to a greater extent than normal-protein (NP) versions. Potential
      mechanisms of action with regard to assessment of eating behaviors across the day
      have not been widely examined during energy restriction.Objectives: The
      objectives of this study were to test whether the consumption of an HP energy
      restriction diet reduces carbohydrate and fat intakes through improvements in
      daily appetite, satiety, and food cravings compared with NP versions and to test
      whether protein type within the NP diets alters protein-related satiety.Methods:
      Seventeen overweight women [mean +/- SEM age: 36 +/- 1 y; body mass index
      (kg/m2): 28.4 +/- 0.1] completed a randomized, controlled-feeding crossover
      study. Participants were provided with the following ~1250-kcal/d energy
      restricted (-750-kcal/d deficit) diets, each for 6 d: HP [124 g protein/d; 60%
      from beef and 40% from plant sources (HP-BEEF)] or NP (48 g protein/d) that was
      protein-type matched (NP-BEEF) or unmatched [100% from plant-based sources (NP
      PLANT)]. On day 6 of each diet period, participants completed a 12-h testing day
      containing repetitive appetite, satiety, and food-craving questionnaires. On day
      7, the participants were asked to consume their protein requirement within each
      respective diet but were provided with a surplus of carbohydrate- and fat-rich
      foods to consume, ad libitum, at each eating occasion across the day. All
      outcomes reported were primary study outcomes.Results: The HP-BEEF diet reduced
      daily hunger by 16%, desire to eat by 15%, prospective food consumption by 14%,
      and fast-food cravings by 15% but increased daily fullness by 25% compared with
      the NP-BEEF and NP-PLANT diets (all P < 0.05). However, consuming more protein
      throughout the day did not reduce the energy consumed ad libitum from the fat-
      and carbohydrate-rich foods (HP-BEEF: 2000 +/- 180 kcal/d; NP-BEEF: 2120 +/- 190
      kcal/d; NP-PLANT: 2070 +/- 180 kcal/d). None of the outcomes differed between the
      NP-BEEF and NP-PLANT treatments.Conclusions: Although appetite control, satiety,
      and food cravings improved after an HP energy-restriction diet, increased protein
      consumption did not reduce carbohydrate and fat intakes throughout the free
      living test day in overweight healthy women exposed to highly palatable foods.
      This trial was registered at clinicaltrials.gov as NCT02614729.

PMID- 29070710
TI  - Carbohydrate Taste Sensitivity Is Associated with Starch Intake and Waist
      Circumference in Adults.
AB  - Background: Recent studies have proposed that humans may perceive complex
      carbohydrates and that sensitivity to simple carbohydrates is independent of
      sensitivity to complex carbohydrates. Variation in oral complex carbohydrate
      sensitivity may influence food consumption.Objective: This study aimed to
      investigate the associations between oral complex carbohydrate sensitivity,
      anthropometry, and dietary intake in adults.Methods: We assessed oral sensitivity
      to complex carbohydrates (maltodextrin and oligofructose) by measuring detection
      thresholds (DTs) and suprathreshold intensity perceptions (STs) for 34
      participants, including 16 men (mean +/- SEM age : 26.2 +/- 0.4 y; range: 24-30
      y) and 18 women (age: 29.4 +/- 2.1 y; range: 24-55 y). We also measured height,
      weight, and waist circumference (WC) and participants completed a 4-d food diary
      and a food-frequency questionnaire.Results: Measurements of oral sensitivity to
      complex carbohydrates were significantly correlated with WC and dietary energy
      and starch intakes (DT: r = -0.38, P < 0.05; ST: r = 0.36-0.48, P < 0.05). When
      participants were grouped into tertiles, there were significant differences in WC
      and total energy or starch intakes for those who were more sensitive or
      experienced high intensity compared with those who were less sensitive or
      experienced low intensity. Being more sensitive or experiencing high intensity
      was associated with greater energy (7968-8954 kJ/d) and starch (29.1-29.8% of
      energy) intakes and a greater WC (88.2-91.4 cm) than was being less sensitive or
      experiencing low intensity (6693-7747 kJ/d, 20.9-22.2% of energy, and 75.5-80.5
      cm, respectively).Conclusion: Complex carbohydrate sensing is associated with WC
      and consumption of complex carbohydrates and energy in adults. This trial was
      registered at anzctr.org.au as ACTRN12616001356459.

PMID- 29070712
TI  - l-Serine Enhances Light-Induced Circadian Phase Resetting in Mice and Humans.
AB  - Background: The circadian clock is modulated by the timing of ingestion or food
      composition, but the effects of specific nutrients are poorly
      understood.Objective: We aimed to identify the amino acids that modulate the
      circadian clock and reset the light-induced circadian phase in mice and
      humans.Methods: Male CBA/N mice were orally administered 1 of 20 l-amino acids,
      and the circadian and light-induced phase shifts of wheel-running activity were
      analyzed. Antagonists of several neurotransmitter pathways were injected before l
      serine administration, and light-induced phase shifts were analyzed. In addition,
      the effect of l-serine on the light-induced phase advance was investigated in
      healthy male students (mean +/- SD age 22.2 +/- 1.8 y) by using dim-light
      melatonin onset (DLMO) determined by saliva samples as an index of the circadian
      phase.Results: l-Serine administration enhanced light-induced phase shifts in
      mice (1.86-fold; P < 0.05). Both l-serine and its metabolite d-serine, a
      coagonist of N-methyl-d-aspartic acid (NMDA) receptors, exerted this effect, but
      d-serine concentrations in the hypothalamus did not increase after l-serine
      administration. The effect of l-serine was blocked by picrotoxin, an antagonist
      of gamma-aminobutyric acid A receptors, but not by MK801, an antagonist of NMDA
      receptors. l-Serine administration altered the long-term expression patterns of
      clock genes in the suprachiasmatic nuclei. After advancing the light-dark cycle
      by 6 h, l-serine administration slightly accelerated re-entrainment to the
      shifted cycle. In humans, l-serine ingestion before bedtime induced significantly
      larger phase advances of DLMO after bright-light exposure during the morning
      (means +/- SEMs-l-serine: 25.9 +/- 6.6 min; placebo: 12.1 +/- 7.0 min; P <
      0.05).Conclusion: These results suggest that l-serine enhances light-induced
      phase resetting in mice and humans, and it may be useful for treating circadian
      disturbances.

PMID- 29070711
TI  - Dietary B Vitamin Intake Is Associated with Lower Urinary Monomethyl Arsenic and
      Oxidative Stress Marker 15-F2t-Isoprostane among New Hampshire Adults.
AB  - Background: Arsenic exposure has been associated with an increased risk of
      cardiovascular disease (CVD). Growing evidence suggests that B vitamins
      facilitate arsenic metabolism and may protect against arsenic toxicity. However,
      to our knowledge, few studies have evaluated this in US populations.Objective:
      Our objective was to examine whether higher B vitamin intake is associated with
      enhanced arsenic metabolism and lower concentrations of preclinical markers of
      CVD among New Hampshire adults.Methods: We used weighted quantile sum (WQS)
      regression to evaluate the collective impact of 6 dietary B vitamins (thiamin,
      riboflavin, folate, niacin, and vitamins B-6 and B-12) on 1) the proportion of
      arsenic metabolites in urine and 2) 6 CVD-related markers [including urinary 15
      F2t-isoprostane (15-F2t-IsoP)] among 418 participants (26-75 y of age) from the
      New Hampshire Health Study. Contributions of arsenic metabolites to B vitamin-CVD
      marker associations were also explored in structural equation models.Results: In
      WQS models, the weighted sum of B vitamin intakes from food sources was inversely
      associated with the proportion of monomethyl arsenic species in urine (uMMA)
      (beta: -1.03; 95% CI: -1.91, -0.15; P = 0.02). Thiamin and vitamins B-6 and B-12
      contributed the most to this association, whereas riboflavin had a negligible
      effect. Higher overall B vitamin intake was also inversely associated with 15-F2t
      IsoP (beta: -0.21; 95% CI: -0.32, -0.11; P < 0.01), with equal contributions from
      the 6 B vitamins, which was partially explained by differences in the proportion
      of uMMA (indirect effect beta: -0.01; 95% CI: -0.04, -0.00).Conclusions: Among
      New Hampshire adults, higher intakes of certain B vitamins (particularly thiamin
      and vitamins B-6 and B-12 from food sources) may reduce the proportion of uMMA,
      an intermediate of arsenic metabolism that has been associated with an increased
      risk of CVD. Higher overall B vitamin intake may also reduce urinary 15-F2t-IsoP,
      a marker of oxidative stress and potential risk factor for CVD, in part by
      reducing the proportion of uMMA.

PMID- 29070714
TI  - Statins and the Risk of Intracerebral Hemorrhage in Patients With Previous
      Ischemic Stroke or Transient Ischemic Attack.
AB  - BACKGROUND AND PURPOSE: Although there is no overall association between statin
      use and intracerebral hemorrhage (ICH), whether there is an increased risk among
      those with a history of ischemic stroke (IS) or transient ischemic attack (TIA)
      remains controversial. We evaluated the relationship of preadmission statin use
      with the risk of ICH in patients with a history of IS or TIA in a population
      based cohort. METHODS: The Health Improvement Network primary care database in
      the United Kingdom was used to identify new users of low-dose aspirin and a
      matched comparison. Both cohorts were followed to identify incident cases of ICH,
      with validation by manual review of patient records and linkage to
      hospitalization data. In a nested case-control study, we compared the adjusted
      odds ratios (ORs) with 95% confidence intervals (CIs) for ICH based on statin use
      in the subgroup of individuals with history of IS/TIA. RESULTS: Last statin use
      within 1 year of ICH (OR, 0.92; 95% CI [confidence interval], 0.60-1.4), last use
      between 8 days and 1 year (OR, 1.81; 95% CI, 0.99-3.28), and statin use at the
      time of ICH (OR, 0.77; 95% CI, 0.49-1.21) were not associated with the overall
      ICH risk among 157 patients with ICH and 884 controls with a history of IS/TIA.
      There was also no difference in 30-day rates of fatal (OR, 0.82; 95% CI, 0.41
      1.64) or nonfatal (OR, 0.90; 95% CI, 0.51-1.57) ICH. CONCLUSIONS: Statin use was
      not associated with an increased risk of ICH among patients with a previous
      history of IS/TIA.

PMID- 29070713
TI  - Long-Term Intake of a High-Protein Diet Affects Body Phenotype, Metabolism, and
      Plasma Hormones in Mice.
AB  - Background: High-protein diets (HPDs) recently have been used to obtain body
      weight and fat mass loss and expand muscle mass. Several studies have documented
      that HPDs reduce appetite and food intake.Objective: Our goal was to determine
      the long-term effects of an HPD on body weight, energy intake and expenditure,
      and metabolic hormones.Methods: Male C57BL/6 mice (8 wk old) were fed either an
      HPD (60% of energy as protein) or a control diet (CD; 20% of energy as protein)
      for 12 wk. Body composition and food intakes were determined, and plasma hormone
      concentrations were measured in mice after being fed and after overnight feed
      deprivation at several time points.Results: HPD mice had significantly lower body
      weight (in means +/- SEMs; 25.73 +/- 1.49 compared with 32.5 +/- 1.31 g; P =
      0.003) and fat mass (9.55% +/- 1.24% compared with 15.78% +/- 2.07%; P = 0.05)
      during the first 6 wk compared with CD mice, and higher lean mass throughout the
      study starting at week 2 (85.45% +/- 2.25% compared with 75.29% +/- 1.90%; P =
      0.0001). Energy intake, total energy expenditure, and respiratory quotient were
      significantly lower in HPD compared with CD mice as shown by cumulative energy
      intake and eating rate. Water vapor was significantly higher in HPD mice during
      both dark and light phases. In HPD mice, concentrations of leptin [feed-deprived:
      41.31 +/- 11.60 compared with 3041 +/- 683 pg/mL (P = 0.0004); postprandial:
      112.5 +/- 102.0 compared with 8273 +/- 1415 pg/mL (P < 0.0001)] and glucagon-like
      peptide 1 (GLP-1) [feed-deprived: 5.664 +/- 1.44 compared with 21.31 +/- 1.26
      pg/mL (P = <0.0001); postprandial: 6.54 +/- 2.13 compared with 50.62 +/- 11.93
      pg/mL (P = 0.0037)] were significantly lower, whereas postprandial glucagon
      concentrations were higher than in CD-fed mice.Conclusions: In male mice, the 12
      wk HPD resulted in short-term body weight and fat mass loss, but throughout the
      study preserved body lean mass and significantly reduced energy intake and
      expenditure as well as leptin and GLP-1 concentrations while elevating
      postprandial glucagon concentrations. This study suggests that long-term use of
      HPDs may be an effective strategy to decrease energy intake and expenditure and
      to maintain body lean mass.

PMID- 29070716
TI  - PLUMBER Study (Prevalence of Large Vessel Occlusion Strokes in Mecklenburg County
      Emergency Response).
AB  - BACKGROUND AND PURPOSE: The recently proposed American Heart Association/American
      Stroke Association EMS triage algorithm endorses routing patients with suspected
      large vessel occlusion (LVO) acute ischemic strokes directly to endovascular
      centers based on a stroke severity score. The predictive value of this algorithm
      for identifying LVO is dependent on the overall prevalence of LVO acute ischemic
      stroke in the EMS population screened for stroke, which has not been reported.
      METHODS: We performed a cross-sectional study of patients transported by our
      county's EMS agency who were dispatched as a possible stroke or had a primary
      impression of stroke by paramedics. We determined the prevalence of LVO by
      reviewing medical record imaging reports based on a priori specified criteria.
      RESULTS: We enrolled 2402 patients, of whom 777 (32.3%) had an acute stroke
      related diagnosis. Among 485 patients with acute ischemic stroke, 24.1% (n=117)
      had an LVO, which represented only 4.87% (95% confidence interval, 4.05%-5.81%)
      of the total EMS population screened for stroke. CONCLUSIONS: Overall, the
      prevalence of LVO acute ischemic stroke in our EMS population screened for stroke
      was low. This is an important consideration for any EMS stroke severity-based
      triage protocol and should be considered in predicting the rates of overtriage to
      endovascular stroke centers.

PMID- 29070715
TI  - Prevalence and Natural History of Superficial Siderosis: A Population-Based
      Study.
AB  - BACKGROUND AND PURPOSE: Superficial siderosis (SS) is characterized by
      hemosiderin deposition in the superficial layers of the central nervous system
      and can be seen during postmortem examination or with iron-sensitive magnetic
      resonance imaging techniques. The distribution of SS may predict the probable
      underlying cause. This study aimed to report the prevalence and natural history
      of SS in a population-based study. METHODS: Brain magnetic resonance imaging
      scans from the MCSA (Mayo Clinic Study of Aging), a population-based study of
      residents 50 to 89 years of age in Olmsted County, Minnesota, were reviewed.
      Participants with imaging consistent with SS were identified from 2011 through
      2016. An inverse probability weighting approach was used to convert our observed
      frequencies to population prevalence of SS. Additional data abstracted included
      amyloid positron emission tomography, Apolipoprotein E genotype, coexisting
      cerebral microbleeds, and extent of SS. RESULTS: A total of 1412 participants had
      eligible magnetic resonance imaging scans. Two participants had infratentorial
      SS, restricted to the posterior fossa. Thirteen participants had cortical SS
      involving the cerebral convexities (7 focal and 6 disseminated). Only 3 of the
      participants with cortical SS (23%) also had cerebral microbleeds. The population
      prevalence of SS was 0.21% (95% confidence interval, 0-0.45) in those 50 to 69
      years old and 1.43% (confidence interval, 0.53-2.34) in those over 69 years old.
      Apolipoprotein E epsilon2 allele was more common in those with SS (57.1% versus
      15.0%; P<0.001). Compared with participants without SS, those with SS were also
      more likely to have a positive amyloid positron emission tomographic scan (76.9%
      versus 29.8%; P<0.001). CONCLUSIONS: SS may be encountered in the general elderly
      population. The association with increased amyloid burden and Apolipoprotein E
      epsilon2 genotype supports cerebral amyloid angiopathy as the most common
      mechanism. Longitudinal follow-up is needed to evaluate the risk of subsequent
      hemorrhage in cases of incidentally discovered SS.

PMID- 29070717
TI  - Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic
      Stroke.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke is a major health problem worldwide, but
      the influence of dietary factors on stroke risk is not well known. This study
      aimed to investigate the risk of ischemic stroke and its subtypes with a higher
      intake from linoleic acid and a concomitant lower intake from saturated fatty
      acids, monounsaturated fatty acids, or glycemic carbohydrates. METHODS: In the
      Danish prospective Diet, Cancer, and Health Study of 57 053 participants aged 50
      to 64 years at baseline, information on diet was collected using a validated
      semiquantitative food frequency questionnaire. Information on ischemic stroke was
      obtained from the Danish National Patient Register, and cases were all validated
      and subclassified according to the TOAST (Trial of ORG 10172 in Acute Stroke
      Treatment) classification. Substitution of linoleic acid for saturated fatty
      acid, monounsaturated fatty acid, or glycemic carbohydrates was investigated in
      relation to the risk of ischemic stroke and subtypes. Cox proportional hazards
      regression was used to estimate the associations with ischemic stroke adjusting
      for appropriate confounders. RESULTS: During 13.5 years of follow-up 1879
      participants developed ischemic stroke. A slightly lower risk of ischemic stroke
      was found with a 5% higher intake of linoleic acid and a concomitant lower intake
      of saturated fatty acid (hazard ratio, 0.98; 95% confidence interval, 0.83-1.16),
      monounsaturated fatty acid (hazard ratio, 0.80; 95% confidence interval, 0.63
      1.02), and glycemic carbohydrates (hazard ratio, 0.92; 95% confidence interval,
      0.78-1.09), although not statistically significant. Similar patterns of
      association were found for large-artery atherosclerosis and small-vessel
      occlusions. CONCLUSIONS: This study suggests that replacing saturated fatty acid,
      glycemic carbohydrate, or monounsaturated fatty acid with linoleic acid may be
      associated with a lower risk of ischemic stroke.

PMID- 29070718
TI  - Phylogenetically informed spatial planning is required to conserve the mammalian
      tree of life.
AB  - In the face of the current extinction crisis and severely limited conservation
      resources, safeguarding the tree of life is increasingly recognized as a high
      priority. We conducted a first systematic global assessment of the conservation
      of phylogenetic diversity (PD) that uses realistic area targets and highlights
      the key areas for conservation of the mammalian tree of life. Our approach offers
      a substantially more effective conservation solution than one focused on species.
      In many locations, priorities for PD differ substantially from those of a species
      based approach that ignores evolutionary relationships. This discrepancy
      increases rapidly as the amount of land available for conservation declines, as
      does the relative benefit for mammal conservation (for the same area protected).
      This benefit is equivalent to an additional 5900 Myr of distinct mammalian
      evolution captured simply through a better informed choice of priority areas. Our
      study uses area targets for PD to generate more realistic conservation scenarios,
      and tests the impact of phylogenetic uncertainty when selecting areas to
      represent diversity across a phylogeny. It demonstrates the opportunity of using
      rapidly growing phylogenetic information in conservation planning and the
      readiness for a new generation of conservation planning applications that
      explicitly consider the heritage of the tree of life's biodiversity.

PMID- 29070719
TI  - Higher iridescent-to-pigment optical effect in flowers facilitates learning,
      memory and generalization in foraging bumblebees.
AB  - Iridescence-change of colour with changes in the angle of view or of illumination
      is widespread in the living world, but its functions remain poorly understood.
      The presence of iridescence has been suggested in flowers where diffraction
      gratings generate iridescent colours. Such colours have been suggested to serve
      plant-pollinator communication. Here we tested whether a higher iridescence
      relative to corolla pigmentation would facilitate discrimination, learning and
      retention of iridescent visual targets. We conditioned bumblebees (Bombus
      terrestris) to discriminate iridescent from non-iridescent artificial flowers and
      we varied iridescence detectability by varying target iridescent relative to
      pigment optical effect. We show that bees rewarded on targets with higher
      iridescent relative to pigment effect required fewer choices to complete
      learning, showed faster generalization to novel targets exhibiting the same
      iridescence-to-pigment level and had better long-term memory retention. Along
      with optical measurements, behavioural results thus demonstrate that bees can
      learn iridescence-related cues as bona fide signals for flower reward. They also
      suggest that floral advertising may be shaped by competition between iridescence
      and corolla pigmentation, a fact that has important evolutionary implications for
      pollinators. Optical measurements narrow down the type of cues that bees may have
      used for learning. Beyond pollinator-plant communication, our experiments help
      understanding how receivers influence the evolution of iridescence signals
      generated by gratings.

PMID- 29070720
TI  - Mortality risk and social network position in resident killer whales: sex
      differences and the importance of resource abundance.
AB  - An individual's ecological environment affects their mortality risk, which in
      turn has fundamental consequences for life-history evolution. In many species,
      social relationships are likely to be an important component of an individual's
      environment, and therefore their mortality risk. Here, we examine the
      relationship between social position and mortality risk in resident killer whales
      (Orcinus orca) using over three decades of social and demographic data. We find
      that the social position of male, but not female, killer whales in their social
      unit predicts their mortality risk. More socially integrated males have a
      significantly lower risk of mortality than socially peripheral males,
      particularly in years of low prey abundance, suggesting that social position
      mediates access to resources. Male killer whales are larger and require more
      resources than females, increasing their vulnerability to starvation in years of
      low salmon abundance. More socially integrated males are likely to have better
      access to social information and food-sharing opportunities which may enhance
      their survival in years of low salmon abundance. Our results show that observable
      variation in the social environment is linked to variation in mortality risk, and
      highlight how sex differences in social effects on survival may be linked to sex
      differences in life-history evolution.

PMID- 29070721
TI  - Threat and parochialism in intergroup relations: lab-in-the-field evidence from
      rural Georgia.
AB  - Competition between groups is widely considered to foster cooperation within
      groups. Evidence from laboratory experiments hints at the existence of a
      proximate mechanism by which humans increase their level of cooperation with
      their ingroup when faced with an external threat. Further work suggests that
      ingroup cooperation should go along with aggressive behaviour towards the
      outgroup, although these theories are at odds with others that see high
      investments in outgroup relations as important means of stabilizing intergroup
      relations. Surprisingly, few of these arguments have been tested in the field,
      and existing studies are also limited by the lack of a direct measure of threat
      perception and aggressive behaviour. This study presents lab-in-the-field results
      from a rural context where exposure to an ethnic outgroup varies between
      villages. This context makes it possible to capture levels of threat perception,
      aggressive behaviour and cooperation without inducing intergroup competition
      artificially in the laboratory. All concepts are measured behaviourally. In- and
      outgroup cooperation was measured with a standard public goods game, and a novel
      experimental protocol was developed that measures perceived threat and aggressive
      behaviour: the threat game. The results show that levels of perceived threat,
      ingroup cooperation and aggressive behaviour are higher in regions more strongly
      exposed to ethnic outsiders. However, exposed regions also show high levels of
      outgroup cooperation and a concomitant lack of elevated ingroup bias. This
      pattern is explained by theorizing that communities show parochial altruism when
      faced with an ethnic outgroup, but balance aggressive behaviour with cooperative
      offers to diffuse tensions and to keep open channels of mutually beneficial
      exchange.

PMID- 29070722
TI  - A pronounced uterine pro-inflammatory response at parturition is an ancient
      feature in mammals.
AB  - Regulating maternal immunity is necessary for successful human pregnancy. Whether
      this is needed in mammals with less invasive placentation is subject to debate.
      Indeed, the short gestation times in marsupials have been hypothesized to be due
      to a lack of immune regulation during pregnancy. Alternatively, the maternal
      marsupial immune system may be unstimulated in the absence of a highly invasive
      placenta. Transcripts encoding pro-inflammatory cytokines were found to be
      overrepresented in the whole uterine transcriptome at terminal pregnancy in the
      opossum, Monodelphis domestica To investigate this further, immune gene
      transcripts were quantified throughout opossum gestation. Transcripts encoding
      pro-inflammatory cytokines remained relatively low during pre- and peri
      attachment pregnancy stages. Levels dramatically increased late in gestation,
      peaking within 12 h prior to parturition. These results mirror the spike of
      inflammation seen at eutherian parturition but not at attachment or implantation.
      Our results are consistent with the role of pro-inflammatory cytokines at
      parturition being an ancient and conserved birth mechanism in therian mammals.

PMID- 29070723
TI  - Constructive anthropomorphism: a functional evolutionary approach to the study of
      human-like cognitive mechanisms in animals.
AB  - Anthropomorphism, the attribution of human cognitive processes and emotional
      states to animals, is commonly viewed as non-scientific and potentially
      misleading. This is mainly because apparent similarity to humans can usually be
      explained by alternative, simpler mechanisms in animals, and because there is no
      explanatory power in analogies to human phenomena when these phenomena are not
      well understood. Yet, because it is also difficult to preclude real similarity
      and continuity in the evolution of humans' and animals' cognitive abilities, it
      may not be productive to completely ignore our understanding of human behaviour
      when thinking about animals. Here we propose that in applying a functional
      approach to the evolution of cognitive mechanisms, human cognition may be used to
      broaden our theoretical thinking and to generate testable hypotheses. Our goal is
      not to 'elevate' animals, but rather to find the minimal set of mechanistic
      principles that may explain 'advanced' cognitive abilities in humans, and
      consider under what conditions these mechanisms were likely to enhance fitness
      and to evolve in animals. We illustrate this approach, from relatively simple
      emotional states, to more advanced mechanisms, involved in planning and decision
      making, episodic memory, metacognition, theory of mind, and consciousness.

PMID- 29070725
TI  - Upper limits to body size imposed by respiratory-structural trade-offs in
      Antarctic pycnogonids.
AB  - Across metazoa, surfaces for respiratory gas exchange are diverse, and the size
      of those surfaces scales with body size. In vertebrates with lungs and gills,
      surface area and thickness of the respiratory barrier set upper limits to rates
      of metabolism. Conversely, some organisms and life stages rely on cutaneous
      respiration, where the respiratory surface (skin, cuticle, eggshell) serves two
      primary functions: gas exchange and structural support. The surface must be thin
      and porous enough to transport gases but strong enough to withstand external
      forces. Here, we measured the scaling of surface area and cuticle thickness in
      Antarctic pycnogonids, a group that relies on cutaneous respiration. Surface area
      and cuticle thickness scaled isometrically, which may reflect the dual roles of
      cuticle in gas exchange and structural support. Unlike in vertebrates, the
      combined scaling of these variables did not match the scaling of metabolism. To
      resolve this mismatch, larger pycnogonids maintain steeper oxygen gradients and
      higher effective diffusion coefficients of oxygen in the cuticle. Interactions
      among scaling components lead to hard upper limits in body size, which
      pycnogonids could evade only with some other evolutionary innovation in how they
      exchange gases.

PMID- 29070724
TI  - Amygdala-midbrain connectivity indicates a role for the mammalian parental care
      system in human altruism.
AB  - Costly altruism benefitting a stranger is a rare but evolutionarily conserved
      phenomenon. This behaviour may be supported by limbic and midbrain circuitry that
      supports mammalian caregiving. In rodents, reciprocal connections between the
      amygdala and the midbrain periaqueductal grey (PAG) are critical for generating
      protective responses toward vulnerable and distressed offspring. We used
      functional and structural magnetic resonance imaging to explore whether these
      regions play a role in supporting costly altruism in humans. We recruited a rare
      population of altruists, all of whom had donated a kidney to a stranger, and
      measured activity and functional connectivity of the amygdala and PAG as
      altruists and matched controls responded to care-eliciting scenarios. When these
      scenarios were coupled with pre-attentive distress cues, altruists' sympathy
      corresponded to greater activity in the left amygdala and PAG, and functional
      connectivity analyses revealed increased coupling between these regions in
      altruists during this epoch. We also found that altruists exhibited greater
      fractional anisotropy within the left amygdala-PAG white matter tract. These
      results, coupled with previous evidence of altruists' increased amygdala-linked
      sensitivity to distress, are consistent with costly altruism resulting from
      enhanced care-oriented responses to vulnerability and distress that are supported
      by recruitment of circuitry that supports mammalian parental care.

PMID- 29070726
TI  - The genomics of recovery from coral bleaching.
AB  - Ecological damage from periodic environmental extremes is often repaired in
      resilient ecosystems, but the rate of return to a non-damaged state is critical.
      Measures of recovery of communities include biomass, productivity and diversity,
      while measures of recovery of individuals tend to focus on physiological
      conditions and the return to normal metabolic functioning. Transcriptomics offers
      a window into the entire physiology of the organism under stress and can
      represent a holistic view of organismal recovery. In this study, we track the
      recovery of seven colonies of Acropora hyacinthus following a natural bleaching
      event. We identified a large environmental stress response in the field that
      involved approximately 20% of the host transcriptome. The transcriptome remained
      largely perturbed for at least six months after temperatures had cooled and four
      months after symbiont populations had recovered. Moreover, a small set of genes
      did not recover to previous expression levels even 12 months after the event,
      about the time that normal growth rates resumed. This study is among the first to
      incorporate transcriptomics into a longitudinal dataset of recovery from
      environmental stress. The data demonstrate large and lasting effects on coral
      physiology long after environmental conditions return to normal and symbiont
      populations recover.

PMID- 29070727
TI  - Sleep macrostructure is modulated by positive and negative social experience in
      adult pet dogs.
AB  - The effects of emotionally valenced events on sleep physiology are well studied
      in humans and laboratory rodents. However, little is known about these effects in
      other species, despite the fact that several sleep characteristics differ across
      species and thus limit the generalizability of such findings. Here we studied the
      effect of positive and negative social experiences on sleep macrostructure in
      dogs, a species proven to be a good model of human social cognition. A non
      invasive polysomnography method was used to collect data from pet dogs (n = 16)
      participating in 3-hour-long sleep occasions. Before sleep, dogs were exposed to
      emotionally positive or negative social interactions (PSI or NSI) in a within
      subject design. PSI consisted of petting and ball play, while NSI was a mixture
      of separation, threatening approach and still face test. Sleep macrostructure was
      markedly different between pre-treatment conditions, with a shorter sleep latency
      after NSI and a redistribution of the time spent in the different sleep stages.
      Dogs' behaviour during pre-treatments was related to the macrostructural
      difference between the two occasions, and was further modulated by individual
      variability in personality. This result provides the first direct evidence that
      emotional stimuli affect subsequent sleep physiology in dogs.

PMID- 29070728
TI  - How we perceive our own retina.
AB  - Ever since the days of Rene Descartes, in the seventeenth century, the search for
      the relationship between subjective perception and neural activity has been an
      ongoing challenge. In neuroscience, an approach to the problem via the visual
      system has produced a paradigm using perceptual suppression, changing with time.
      Cortical areas in which the neural activity was modulated in temporal correlation
      with this percept could be traced. Although these areas may lead directly to
      perception, such temporal correlation of neural activity does not suffice as
      ultimate proof that they actually do so. In this article, I will use a different
      method to show that, for the perception of our own retina, any brain area leading
      directly to this perception also needs to represent the retina without
      distortion. Furthermore, I will demonstrate that the phenomenon of size constancy
      must be realized in this area.

PMID- 29070730
TI  - A novel caloric restriction mediator.

PMID- 29070729
TI  - Can't live with them, can't live without them? Balancing mating and competition
      in two-sex populations.
AB  - Two-sex populations are usually studied through frequency-dependent models that
      describe how sex ratio affects mating, recruitment and population growth.
      However, in two-sex populations, mating and recruitment should also be affected
      by density and by its interactions with the sex ratio. Density may have positive
      effects on mating (Allee effects) but negative effects on other demographic
      processes. In this study, we quantified how positive and negative inter-sexual
      interactions balance in two-sex populations. Using a dioecious grass (Poa
      arachnifera), we established experimental field populations that varied in
      density and sex ratio. We then quantified mating success (seed fertilization) and
      non-mating demographic performance, and integrated these responses to project
      population-level recruitment. Female mating success was positively density
      dependent, especially at female-biased sex ratios. Other demographic processes
      were negatively density-dependent and, in some cases, frequency-dependent.
      Integrating our experimental results showed that mate-finding Allee effects
      dominated other types of density-dependence, giving rise to recruitment that
      increased with increasing density and peaked at intermediate sex ratios,
      reflecting tension between seed initiation (greater with more females) and seed
      viability (greater with more males). Our results reveal, for the first time, the
      balance of positive and negative inter-sexual interactions in sex-structured
      populations. Models that account for both density- and sex ratio dependence,
      particularly in mating, may be necessary for understanding and predicting two-sex
      population dynamics.

PMID- 29070731
TI  - Neuronal tetraploidy in Alzheimer and aging.

PMID- 29070733
TI  - LAPAROSCOPIC RADICAL NEPHRECTOMY FOR LARGE RENAL CELL CARCINOMA: RETROSPECTIVE
      ANALYSIS OF SAFETY AND ONCOLOGICAL OUTCOME.
AB  - (Objectives) To evaluate the safety and oncologic efficacy of laparoscopic
      radical nephrectomy (LRN) for renal cell carcinoma (RCC) >7 cm, we
      retrospectively reviewed the clinical outcome and long-term cancer control of
      patients who underwent LRN in comparison to open radical nephrectomy (ORN).
      (Patients and methods) The clinical records of 79 patients with RCC >7 cm, who
      underwent radical nephrectomy (37 LRN; 42 ORN) between 1993 and 2014, were
      reviewed. (Results) The 2 groups (LRN and ORN) were comparable regarding age,
      body mass index and mean tumor size (86.5 mm vs. 94.6 mm).The operative time was
      significantly longer in the LRN group than ORN group (204 min vs. 168 min;
      p<0.05) and blood loss was significantly lower in the LRN group than in the ORN
      group (144 ml vs. 930 ml; p<0.05).No statistically significant difference was
      found in complication rate (10.8% vs. 23.8%) and the 2-year recurrence-free
      survival rate (85.6% vs. 83.8%). (Conclusion) Despite the longer operative time,
      LRN for large RCC was associated with lower blood loss. This study provides
      evidence of the safety and efficacy of LRN for large RCC.

PMID- 29070732
TI  - Thyroid status and mortality in nonagenarians from long-lived families and the
      general population.
AB  - The relationship between thyroid status and longevity has been investigated
      extensively. However, data on thyroid status and survival in old age is scarce.
      In this study we investigated associations of different parameters of thyroid
      status with mortality in nonagenarians, and whether these associations were
      different in nonagenarians from long-lived families than in nonagenarians from
      the general population. In total, 805 nonagenarians from the Leiden Longevity
      Study and 259 nonagenarians from the Leiden 85-plus Study were followed up to
      collect mortality data. At baseline, levels of thyrotropin (TSH), free thyroxine
      (fT4) and free triiodothyronine (fT3) were measured. In nonagenarians from long
      lived families and from the general population, associations between thyroid
      parameters and mortality were similar. We found no interaction between study
      population and parameters of thyroid status on mortality (P-values>0.70). The
      results from both studies were combined to derive generalizable associations.
      Hazard ratios (HRs) for the highest compared to lowest tertiles were determined,
      resulting in TSH HR 0.91 (P=0.25), fT4 HR 1.22 (P=0.02), fT3 HR 0.74 (P=1.31e-4),
      and fT3/fT4 HR 0.66 (P=5.64e-7). In conclusion, higher fT3/fT4 ratios, higher
      levels of fT3, and lower levels of fT4 were associated with lower mortality rate
      in nonagenarians and independent of familial longevity status.

PMID- 29070734
TI  - MID-TERM ONCOLOGICAL OUTCOME AND TECHNICAL MODIFICATIONS FOR LAPAROSCOPIC RADICAL
      CYSTECTOMY AT OUR INSTITUTION: 60 CASES ANALYSIS.
AB  - (Objective) Although laparoscopic radical cystectomy (LRC) is becoming a standard
      care for invasive and high-risk non-invasive bladder cancer in Japan, the data
      about mid-and long-term oncological outcome is still lacking. We previously
      reported our initial experience of LRC compared to open radical cystectomy. In
      this study, we evaluated mid-term oncological outcome for LRC by updating our
      clinical data. In addition, we evaluated the effect of technical modifications
      for LRC. (Patients and methods) From March 2005 to September 2015, 60 patients
      underwent LRC at our institution. Treatment outcomes including surgical and
      oncological outcomes were analyzed. We also assessed the effect of technical
      modifications between first 30 cases and second 30 cases as to blood loss,
      operating time and complication rate. (Results) The overall complication rate was
      47%, including 18% serious complications (Clavien score 3 or greater). The 5-year
      recurrence-free survival, cancer-specific survival, and overall survival were
      56.2%, 74.4%, and 63.6%, respectively. The recurrence occurred in 19 (32%) cases,
      including distant metastasis in 12 (20%) cases, local recurrence in 6 (10%)
      cases, and both in 1 (2%) cases. As for the effect of technical modifications for
      LRC, the blood loss decreased and postoperative recovery was faster in second 30
      cases. (Conclusion) These results indicate that LRC could be performed safely
      with acceptable oncological outcomes.

PMID- 29070735
TI  - URETHROPLASTY FOR COMPLICATED ANTERIOR URETHRAL STRICTURES.
AB  - (Objectives) To compare efficacy and outcome of urethroplasty for complicated
      anterior urethral strictures. (Methods) Twelve patients, included 3 boys, with
      anterior urethral stricture underwent urethroplasty after the failure of either
      urethral dilatation or internal urethrotomy. We evaluated pre- and post-operative
      Q max and surgical outcome. (Results) Four patients were treated with end-to-end
      anastomosis, included a case of bulbar urethral elongation simultaneously, one
      patient was treated with augmented anastomotic urethroplasty, three patients were
      treated with onlay urethroplasty with prepucial flap, one patient was treated
      with tubed urethroplasty with prepucial flap (Ducket procedure) and three
      patients were treated with onlay urethroplasty with buccal mucosal graft.
      Postoperative Qmax improved in all patients without major complications and
      recurrence during follow-up periods ranging from 17 to 102 months (mean 55
      months). (Conclusions) Urethroplasty is an effective therapeutic procedure for
      complicated anterior urethral stricture.

PMID- 29070736
TI  - ASSOCIATION BETWEEN THE RISK OF TESTICULAR TORSION AMONG ACUTE SCROTUM AND
      AMBIENT TEMPERATURE.
AB  - (Objectives) Testicular torsion (TT) is a socially and clinically important
      urological emergency condition because delayed diagnosis and treatment can lead
      to testicular loss. Although a possible association between TT and low ambient
      temperature has been argued, the clinical significance of the association has not
      been fully elucidated. We retrospectively collected acute scrotum cases and
      investigated the association between the risk of TT among acute scrotums and
      ambient temperatures on the day of onset. (Patients and methods) We studied 105
      consecutive acute scrotum patients with suspected TT who underwent urgent
      surgical exploration between October 2004 and October 2014. The patients' age,
      residential area, time and date of onset, laboratory findings, and operative
      findings were collected from their medical records. Climate data, including daily
      mean ambient temperature (DMAT), diurnal temperature change (DTC), humidity, and
      atmospheric pressure at the time of onset, were obtained from the Japan
      Meteorological Agency website. The chi-square and Wilcoxon rank sum tests were
      used to evaluate statistical differences. Logistic regression analysis used to
      identify significant predictors of TT. (Results) The median age of the patients
      was 13 years (range, 1-43 years). The affected side was the right/left/bilateral
      side in 46/58/1 of the patients. Surgical exploration revealed TT in 67 patients.
      The remaining 38 non-TT patients included 12 with testicular appendage torsions,
      12 with epididymal appendage torsions, 9 with epididymitis, 2 with orchitis, 2
      with idiopathic hematomas, and 1 with allergic purpura. The median DMATs at the
      day of onset were 10.8 degrees C (1.8-29.4 degrees C) in the TT patients and 19.4
      degrees C (1.9-29.1 degrees C) in the non-TT patients. The incidence of TT among
      the patients with acute scrotum explored surgically (TT incidence) in days with
      DMATs <15 degrees C (80%) was significantly higher than that in days with DMATs
      >= 15 degrees C (45%; p<0.001). During days with DMATs >=15 degrees C, the TT
      incidence in days with DTCs >=10 degrees C (62%) was significantly higher than
      that in days with DTCs <10 degrees C (32%; p=0.037). Multivariate analysis
      revealed higher age (>=14), low serum C-reactive protein level (<0.5 ng/ml) and
      low DMAT (<15 degrees C) were significant risk factor for TT in patients with
      acute scrotum undergoing surgery. (Conclusions) It should be noted that in this
      study, the onset of acute scrotum during days with low ambient temperatures or
      large DTCs was associated with a moderate to high possibility of TT.

PMID- 29070737
TI  - UROLOGIC DISEASES IN THE EMERGENCY DEPARTMENT.
AB  - (Objectives) This paper aimed to report the clinical statistics on urologic
      diseases treated in the emergency department (ED). (Patients and methods) We
      retrospectively evaluated 1,480 patients diagnosed with urologic diseases in the
      ED between January 2013 and December 2014. We reviewed the patients' sex, age,
      main complaints, emergency grade, care-seeking process, hospitalization,
      examination items, and diagnosis. We also reviewed the correct-diagnosis rates of
      patients who visited the ED for the first time and were followed up at the
      urology department. (Results) Of the patients, 2.6% were diagnosed as having a
      urologic disease, with a male-to-female ratio of 1.5:1. The age distribution
      ranged from 0 to 101 years, with a median age of 53 years. Patients who required
      hospitalization accounted for 17.8%. The diagnoses were urolithiasis (546 cases),
      cystitis (220 cases), and pyelonephritis (137 cases), in order of frequency. The
      correct-diagnosis rates of urolithiasis (91.2%), benign prostatic hyperplasia
      (75.0%), and pyelonephritis (71.9%) were high. However, those of testicular
      torsion (0%), urologic neoplasm (26.7%), prostatitis (35.7%), and epididymitis
      (35.7%) were low. (Conclusion) In the ED, 82.2% of cases of urologic diseases
      were mild and did not require hospitalization. The correct-diagnosis rate of
      acute scrotum was low, as it was difficult to diagnose and thus difficult to
      manage in the ED. Therefore, urologists should cooperate with ED staff and warn
      them that cases of acute scrotum should be subjected to emergency consultation.

PMID- 29070738
TI  - PHEOCHROMOCYTOMA DURING PREGNANCY-2 CASE REPORTS.
AB  - (Introduction) A pheochromocytoma diagnosed during pregnancy is rare, and also
      its fetal and maternal mortality is high if undiagnosed. We report two cases with
      successful pregnancy outcome with pheochromocytoma. (Case 1) A 31-years-old
      previously healthy woman presented at 19 week period of gestation with high blood
      pressure. High urine catecholamine level and a left adrenal mass recognized by
      magnetic resonance imaging (MRI) confirmed adrenal pheochromocytoma. The patient
      had good blood pressure control after we started doxazosin 4 mg daily, and
      Caesarean section was performed at 35 week period of gestation. Two months after
      delivery, laparoscopic adrenalectomy was performed and she was discharged in the
      absence of hypertension. (Case 2) A 31-years-old previously healthy woman
      presented at 29 week period of gestation with exacerbation of headache and
      palpitation. High urine catecholamine level and a mass recognized close to the
      inferior vena cava by MRI confirmed extraadrenal pheochromocytoma. The patient
      had good blood pressure after we started doxazosin 4 mg daily and labetalol
      hydrochloride 200 mg daily. Caesarean section was performed at 35 week period of
      gestation. One month after delivery, laparotomic resection of the tumor was
      performed. Seven years later, hypertension reoccurred and there was an
      extraadrenal pheochromocytoma recurrence. We had a laparotomic resection for the
      recurrent tumor, and now she is in the absence of hypertension. (Conclusion)
      Pheochromocytoma should be considered as a differential diagnosis in a case of
      high blood pressure occurred during pregnancy. Early detection and appropriate
      treatment is crucial to reduce fetal and maternal mortality.

PMID- 29070739
TI  - METANEPHRIC ADENOMA DIAGNOSED PREOPERATIVELY AS RENAL CELL CARCINOMA: A REPORT OF
      TWO CASES.
AB  - Metanephric adenoma is an extremely rare benign tumor. We report two cases of
      metanephric adenoma that were diagnosed preoperatively as renal cell carcinoma
      (RCC).Case 1 was a right renal tumor found by ultrasonography in a 57-year old
      woman who presented for a medical examination. Abdominal CT revealed a 26-mm mass
      that was enhanced weakly in the early phase and enhanced strongly in the late
      phase, in the right kidney. Based on a clinical diagnosis of RCC (cT1aN0M0),
      laparoscopic partial nephrectomy was performed. Case 2 was a left renal tumor
      incidentally found during an annual examination of a 79-year old woman with a
      past history of breast cancer. Abdominal CT revealed a 24-mm mass that was
      enhanced heterogeneously in the left kidney. Based on a clinical diagnosis of RCC
      (cT1aN0M0), laparoscopic radical nephrectomy was performed. The pathological
      diagnosis of both cases was metanephric adenoma.It is often difficult to
      distinguish metanephric adenoma from other malignant neoplasms preoperatively.
      When it is difficult to distinguish between renal cell carcinoma and metanephric
      adenoma, renal tumor biopsy and minimal surgery is required.

PMID- 29070740
TI  - A PATIENT WITH RETROPERITONEAL MYXOID LIPOSARCOMA RECURRENCE WHO ACHIEVED
      REMARKABLE IMPROVEMENTS IN PERFORMANCE STATUS WHEN TREATED WITH COMBINATION
      CHEMOTHERAPY WITH GEMCITABINE AND DOCETAXEL.
AB  - We report a patient with retroperitoneal myxoid liposarcoma recurrence who
      achieved remarkable improvements in performance status (PS) and maintained stable
      disease for approximately 5 months when treated with combination chemotherapy
      with gemcitabine (GEM) and docetaxel combination chemotherapy (GD). A 51-year-old
      woman was referred to our hospital with the chief complaint of a palpable mass in
      the left side of the abdomen. A retroperitoneal liposarcoma was diagnosed on the
      basis of magnetic resonance imaging and computed tomography results, and tumor
      resection was performed. The histopathological evaluation showed myxoid
      liposarcoma, which was classified as grade 2 according to the French Federation
      of Cancer Centers Sarcoma Group (FNCLCC) system.Two months later, the tumor
      regionally recurred as peritoneal dissemination with rapid growth. Five months
      after the surgery, the growing tumor caused appetite loss and pleural effusion in
      the left lung. GD was administered (800 mg/m2 GEM on days 1 and 8, and 60 mg/m2
      docetaxel on day 8) and 4 cycles were administered.The resulting decrease in
      abdominal girth and in the amount of pleural effusion allowed the patient to
      regain her appetite, and the patient's PS greatly improved from 3 to 1.Initially,
      GD was shown to be effective for the treatment of leiomyosarcoma and pleomorphic
      sarcoma, and it is now recommended as one of the first-line regimens in the
      National Comprehensive Cancer Network guidelines for soft tissue sarcoma
      treatment. The patient in this case showed remarkable improvement in PS after
      tumor recurrence and maintained stable disease for some time, without severe
      adverse effects.

PMID- 29070741
TI  - A CASE REPORT OF PANCREATIC METASTASIS FROM PROSTATE CANCER.
AB  - We report a case of pancreatic metastasis from prostate cancer. A 65 year-old man
      developed gross hematuria, and was found to have a markedly elevated PSA and
      abnormal CT findings indicating mass lesions in bilateral lungs, and pancreatic
      head, and osteoblastic lesions in pelvic bone. He was referred to the department
      of Urology and Gastroenterology at Seirei Hamamatsu General Hospital. Digital
      rectal examination revealed a hen's egg-sized, stony-hard prostate. A systematic
      needle biopsy of the prostate demonstrated adenocarcinoma (Gleason score 4+4=8).
      We diagnosed multiple lung and bone metastases from prostate cancer, and
      suspected that a primary pancreatic ductal carcinoma. The patient was started on
      an androgen deprivation therapy (ADT) with bicalutamide and degarelix. After 4
      months from the initiation of ADT, an MRI of the pancreas showed decreased size
      of the pancreatic head mass from 18 mm to 7 mm in diameter. We concluded that the
      pancreatic head mass was metastasis from prostate cancer, and currently continue
      ADT. Pancreatic metastasis from prostate cancer is very rare, and further
      accumulation of cases will be required.

PMID- 29070742
TI  - A CASE OF A CARCINOSARCOMA OF THE PROSTATE.
AB  - Carcinosarcoma of the prostate is a rare but aggressive tumor characterized by
      combination of malignant epithelial and mesenchymal cells. We encountered a case
      of carcinosarcoma of the prostate. A 78-year-old man with urinary retention was
      diagnosed with benign prostatic hyperplasia on the basis of the ultrasonography
      and rectal examination findings, negative result of prostate biopsy.
      Transurethral resection of the prostate was performed, and the pathological
      diagnosis was carcinosarcoma of the prostate with squamous cell carcinoma. The
      patient died of disease 5 months after the diagnosis of carcinosarcoma. A total
      of 17 cases of carcinosarcoma of the prostate including the present case, have
      been reported in the Japanese literature to date. Herein we review the 17 cases
      and discuss the clinical features.

PMID- 29070743
TI  - TESTIS SPARING SURGERY FOR ADULT MATURE TERATOMA OF THE TESTIS; REPORT OF A CASE.
AB  - A 25-year-old man presented complaining of a painful, left scrotal swelling. He
      first noticed a mass in his left scrotum during childhood, but, in the absence of
      clinical symptoms, did not seek medical attention. We detected a left testicular
      tumor which was elastic, firm and smooth. Serum levels of alpha-fetoprotein
      (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH) were
      all within normal range. Magnetic resonance imaging (MRI) and ultrasound revealed
      a solid tumor with cysts accompanied by intracystic hemorrhage and calcified
      walls. From the above findings, the tumor was suspected to be benign and, we
      therefore planned testis-sparing surgery. We performed tumor enucleation under
      cold ischemia. Since an intraoperative frozen section revealed the tumor to be
      benign, we preserved the remaining testis as planned. The final pathologic
      diagnosis was a mature teratoma without a malignant germ cell component. Evidence
      of recurrence has not been observed five years after the operation. In
      conclusion, when a mature teratoma that has been present since prepuberty is
      suspected in an adult, testis-sparing surgery should be considered.

PMID- 29070744
TI  - Glycyrrhizin inhibits human parainfluenza virus type 2 replication by the
      inhibition of genome RNA, mRNA and protein syntheses.
AB  - The effect of glycyrrhizin on the replication of human parainfluenza virus type 2
      (hPIV-2) was examined. Cell fusion induced by hPIV-2 was inhibited by
      glycyrrhizin, and glycyrrhizin reduced the number of viruses released from the
      cells. Glycyrrhizin did not change cell morphology at 1 day of culture, but
      caused some damage at 4 days, as determined by the effect on actin
      microfilaments. However, it affected the cell viability at 1 day: about 20% of
      the cells were not alive by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay at 1 day of culture. Real-time polymerase chain reaction
      (PCR) and PCR showed that virus genome synthesis was largely inhibited. mRNA
      synthesis was also inhibited by glycyrrhizin. Viral protein synthesis was largely
      inhibited as observed by an indirect immunofluorescence study. Multinucleated
      giant cell formation was studied using a recombinant green fluorescence protein
      (GFP)-expressing hPIV-2 without matrix protein (rhPIV-2DeltaMGFP). A few single
      cells with fluorescence were observed, but the formation of giant cells was
      completely blocked. Taken together, it was shown that viral genome, mRNA and
      protein syntheses, including F and HN proteins, were inhibited by glycyrrhizin,
      and consequently multinucleated giant cell formation was not observed and the
      infectious virus was not detected in the culture medium.

PMID- 29070745
TI  - Incidence, Characteristics and Management of Venous Thromboembolism in Japan
      During 2011.
AB  - BACKGROUND: This study aimed to determine the incidence, characteristics and
      management of venous thromboembolism (VTE) in Japan during 2011.Methods and
      Results:A retrospective study assessed responses to a questionnaire regarding
      treating newly diagnosed VTE at all admitting hospitals throughout Japan during
      2011. More individuals were diagnosed with VTE than ever before, with 16,096
      cases of diagnosed pulmonary embolism (PE) and 24,538 cases of diagnosed deep
      vein thrombosis (DVT). Almost half (47.2%) of the PE patients had a relatively
      mild condition with no right ventricular overload. Similarly, almost half (43.8%)
      of the DVT patients had a relatively mild condition with isolated calf thrombus.
      Most of PE patients were treated by anticoagulation, and fewer were treated using
      thrombolytic agent or inferior vena cava (IVC) filter. CONCLUSIONS: The present
      study showed a remarkable increase in the incidence of VTE in Japan during 2011.
      Relatively mild conditions such as non-massive PE and isolated calf DVT were
      frequently diagnosed. Among PE patients, thrombolytic therapy or IVC filter
      implantation decreased compared with previous surveys. The appropriate management
      of isolated calf DVT requires further investigation.

PMID- 29070748
TI  - [Complimentary use of needle electromyography and ultrasonography of tongue is
      effective for early detection of abnormality in 20 patients with amyotrophic
      lateral sclerosis].
AB  - A group of 20 consecutive patients with amyotrophic lateral sclerosis (ALS) were
      evaluated using electromyography (EMG) and ultrasonography (US) of the tongue.
      Their records were reviewed retrospectively for the rates at which abnormalities
      were detected by these two modalities as well as their clinical features. Visual
      inspection detected abnormalities in 9 of 20 patients, EMG in 12, and US in 6.
      However, EMG detected active denervation earlier than did US in 7 of the 12 EMG
      diagnosed patients, and US detected fasciculation earlier than did EMG in 1 of
      the 6 US-diagnosed patients. Thus, we cannot replace EMG completely with US.
      Indeed, we currently use both methods complementarily at our hospital.

PMID- 29070749
TI  - [A amyotrophic lateral sclerosis (ALS) 4 family misdiagnosed as hereditary
      spastic paraplegia-a case report].
AB  - We report a 44 years old man with slowly progressive muscular atrophy of the
      extremities for over 30 years. He experienced difficulty in walking in his 10's
      and was diagnosed as hereditary spastic paraplegia (HSP) in his 20's. And then,
      muscle atrophy of the extremities slowly progressed especially in his distal
      muscles. Sensory axonal neuropathy was detected with sural nerve biopsy. His
      father and uncle have been diagnosed as HSP in their early days. His father
      noticed weakness of his leg in his 20's. He lost motor function of the leg in his
      60's. In addition, marked disturbance of thermal sensation, vibration, and sense
      of position were found by physical examination. Our genetic study detected
      senataxin (SETX) gene mutation (c.8C>T,p.T3I) in the blood of those two patients,
      and they had been identified as family cases of amyotrophic lateral sclerosis
      (ALS) 4. As clinical symptoms of ALS4 would be similar to those of HSP at the
      onset, we suggest considering ALS4 in seeing patients with HSP without gene
      diagnosis.

PMID- 29070750
TI  - [A case of recurrent myelitis associated with anti-myelin oligodendrocyte
      glycoprotein antibody that developed only as localized short spinal cord
      lesions].
AB  - A 65-year-old man initially developed numbness and hypesthesia in the right
      shoulder and brachial regions that disappeared within several months. MRI
      revealed a small lesion extending to a vertebral segment in the right dorsal
      region of the cervical spinal cord at the vertebral height of C2/3. About 15
      months later, the intermittent lancinating pain identical to the right trigeminal
      and occipital neuralgia with pain and hypesthesia distributed in the right C2-C4
      dermatome regions appeared. MRI revealed a new oval lesion with gadolinium
      enhancement in the right dorsal region of the cervical spinal cord at the
      vertebral height of C1, which was thought to involve the posterior column and
      lower part of the spinal tract nucleus of the trigeminal nerve. There was no
      optic nerve, brain, or other spinal cord lesions that suggested demyelination on
      MRI. A titer of serum anti-aquaporin-4 antibody was negative, but anti-myelin
      oligodendrocyte glycoprotein (MOG) antibody was found to be positive. The
      symptoms were relieved by corticosteroid treatment. Our report presents a rare
      case of anti-MOG antibody-positive recurrent myelitis that developed only as
      localized short upper cervical spinal cord lesions, not meeting the diagnostic
      criteria for neuromyelitis optica spectrum disorders.

PMID- 29070751
TI  - [Two cases of nemaline myopathy presenting with hypertrophy of distal limbs with
      prominent asymmetry].
AB  - Nemaline myopathy commonly presents with symmetrical proximal weakness. Here we
      report two cases of nemaline myopathy presenting with distal dominant involvement
      with prominent asymmetry. Case 1 was a 37-year-old man who recalled frequently
      falling down and had right calf atrophy since he was 3-years-old. He had right
      calf muscle atrophy and weakness and steppage gait; his cardiopulmonary function
      was normal. Case 2 was a 35-year-old man with right calf muscle atrophy and
      weakness since childhood. He had right dominant distal leg weakness and atrophy
      together with respiratory failure and started noninvasive positive pressure
      ventilation. He also developed cardiomyopathy and died from acute respiratory
      failure due to pneumonia at age 39. Both cases harbored compound heterozygous
      nebulin (NEB) mutations with c.20131 C>T:p.Arg6711Trp and a nonsense mutation.
      Nemaline myopathy associated with NEB mutations can present as distal dominant
      myopathy with prominent asymmetry.

PMID- 29070752
TI  - [A surgical case of mesial temporal lobe epilepsy associated with hippocampal
      sclerosis and traumatic neocortical lesion].
AB  - A 26-year-old right-handed woman, with a history of left temporal lobe contusion
      caused by a fall at the age of 9 months, started to have complex partial seizures
      with oral automatism at the age of 7 years. The seizures occurred once or twice a
      month despite combination therapy with several antiepileptic agents. Her history
      and imaging studies suggested the diagnosis of epilepsy arising from traumatic
      neocortical temporal lesion. Comprehensive assessment including long-term video
      EEG monitoring, MRI, FDG-PET, MEG, and neuropsychological evaluation was
      performed at the age of 26 years. The diagnosis was left mesial temporal lobe
      epilepsy associated with hippocampal atrophy and traumatic temporal cortical
      lesion. The patient was readmitted for surgical treatment at the age of 27 years.
      Intracranial EEG monitoring showed that ictal discharges started in the left
      hippocampus and spread to the traumatic lesion in the left posterior superior
      temporal gyrus 10 seconds after the onset. This case could not be classified as
      dual pathology exactly, because the traumatic left temporal cortical lesion did
      not show independent epileptogenicity. However, the traumatic lesion was highly
      likely to be the source of the epileptogenicity, and she had right hemispheric
      dominance for language and functional deterioration in the whole temporal cortex.
      Therefore, left amygdalo-hippocampectomy and left temporal lobectomy including
      the traumatic lesion were performed according to the diagnosis of dual pathology.
      Subsequently, she remained seizure-free for 3 years. Comprehensive assessment of
      seizure semiology, neurophysiology, neuroradiology, and neuropsychology is
      important to determine the optimum therapeutic strategies for drug-resistant
      epilepsy.

PMID- 29070753
TI  - [A case of primary central nervous system anaplastic lymphoma kinase positive
      anaplastic large cell lymphoma manifested as a unilateral pachymeningits].
AB  - There have been 23 reports of primary central nervous system anaplastic lymphoma
      kinase (ALK)-positive anaplastic large cell lymphoma in the literature. Here we
      report the 24th case of a 40-year-old man who presented with occipital headache
      for one month. His contrast-enhanced brain MRI showed enhancement around the
      right temporal lobe, which suggested a diagnosis of hypertrophic pachymeningitis.
      He improved with steroid therapy. After discharge, however, he was readmitted
      with generalized convulsive seizures. Finally, he was diagnosed as primary
      central nervous system ALK-positive anaplastic large cell lymphoma by brain
      biopsy. Primary central nervous system lymphoma invading dura matter can rarely
      manifests as a unilateral pachymeningitis. Therefore, in case of pachymeningitis,
      we should pay attention to the possibility of infiltration of lymophoma with
      meticulous clinical follow-up.

PMID- 29070754
TI  - [A 70-year-old woman presenting with restless shoulder following posterior
      internal capsule infarction].
AB  - A 70-year-old woman noticed difficulty in speech and weakness of the left upper
      and lower limb upon awakening. Neurological examination showed dysarthria and
      left hemiparesis. No sensory disturbance was observed. Brain MRI revealed acute
      infarction in the right posterior limb of the internal capsule. On the hospital
      day 1, she developed the abnormal sensations restricted to the bilateral
      shoulders, resulting in difficulty initiating sleep. On laboratory data, renal
      function and serum hemoglobin and ferritin levels were normal. When four
      essential features of restless legs syndrome (RLS) were applied to her shoulders,
      the patient met RLS criteria. Following low dose pramipexole treatment, the
      abnormal sensation of the shoulders and insomnia significantly improved. We
      should be aware of the possibility of RLS or its variant, including "restless
      shoulder" of our patient, for the cause of insomnia following acute ischemic
      infarction.

PMID- 29070755
TI  - [A case of optic perineuritis-A literature review of Japanese cases and clinical
      problems].
AB  - A 64-year-old woman was admitted to our hospital owing to decreased visual acuity
      and visual field defect. She had a similar history of decreased visual acuity and
      received steroid therapy 10 years ago. Brain MRI revealed gadolinium-enhancement
      in the sheath of the optic nerve, called "tram-track" and "doughnut" signs. Optic
      perineuritis (OPN) was diagnosed on the basis of her clinical manifestations,
      which improved on treatment with high-dose methylprednisolone (mPSL). However,
      clinical manifestations relapsed 10 days post-discharge; hence, she was re
      admitted. She was re-administered high-dose mPSL and subsequent oral
      administration of prednisolone. She had no relapse or recurrence for the last 2
      years. We reviewed studies involving Japanese patients with OPN, including 17
      idiopathic and 14 secondary cases and found that 43% of patients had recurrences
      and 30% of patients had poor outcome including severe residuals of visual acuity.
      Secondary OPN occurred owing to various diseases manifesting generalized
      systematic inflammation. Timely and suitable treatment was very important for
      clinical favorable outcomes in OPN.

PMID- 29070756
TI  - [A case of anti-MOG antibody-positive multiphasic disseminated encephalomyelitis
      co-occurring with unilateral cerebral cortical encephalitis].
AB  - A 20-year-old woman first developed acute disseminated encephalomyelitis (ADEM)
      at 11 years of age. At 17 years of age, she was hospitalized due to generalized
      seizure and diagnosed with encephalitis. Brain MRI revealed a FLAIR-hyperintense
      lesion in the unilateral cerebral cortex. At 18 years of age, serum anti-myelin
      oligodendrocyte glycoprotein (MOG) antibody was detected. At 20 years of age, she
      was admitted to our hospital, diagnosed with multifocal disseminated
      encephalomyelitis (MDEM). MDEM has been observed in patients that are
      seropositive for the anti-MOG antibody. More recently, unilateral cerebral cortex
      encephalitis with epilepsy has also been reported in such patients. The co
      occurrence of MDEM and cortical encephalitis in the same patient has important
      implications for the pathogenesis of anti-MOG antibody-associated autoimmune
      diseases.

PMID- 29070757
TI  - Mitral Valve Systolic Anterior Motion-Associated Sounds in Hypertrophic
      Cardiomyopathy.

PMID- 29070758
TI  - Metabolic Considerations in Atrial Fibrillation - Mechanistic Insights and
      Therapeutic Opportunities.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice and is associated with morbidity and mortality. Over the past 2 decades,
      there have been major advances in understanding AF pathophysiology, but important
      knowledge gaps, particularly about targetable basic mechanisms, remain. Recent
      metabolomic and proteomic studies have shown changes in the expression of
      molecules involved in metabolic pathways in human and experimental AF, indicating
      a role for metabolic alterations in AF pathophysiology. AF is characterized by
      irregular high-frequency excitation and contraction that affect atrial energy
      demands, circulation and oxygen supply, and change the balance between metabolic
      demand and supply, causing metabolic stress. Here, we review the information
      available about AF-induced metabolic changes and their pathophysiological
      contribution. We also discuss the possibilities of developing novel therapeutic
      strategies that act by modulating cardiac metabolic processes during AF.

PMID- 29070759
TI  - Total bilirubin amount in drainage fluid can be an early predictor for severe
      biliary fistula after hepatobiliary surgery.
AB  - The ratio of the bilirubin concentration in abdominal drainage fluid to the serum
      bilirubin concentration (d-Bil/s-Bil) has been used as a predictor of biliary
      fistula (BF) formation after hepatobiliary surgery. The d-Bil/s-Bil ratio is
      highly influenced by the amount of drainage and is not always reliable,
      especially when the amount of drainage is large. In this study, the usefulness of
      the d-Bil/s-Bil ratio and total bilirubin amount in the drainage fluid (TBA)
      (bilirubin concentration in the drainage fluid x the amount of drainage) as
      predictors of severe BF (sBF) formation was evaluated retrospectively from the
      data of 306 patients who had undergone hepatobiliary surgery. Of the 306
      patients, 201 patients were included in the training set and the remaining 105 in
      the validation set, to determine the best parameter to predict sBF formation
      after hepatobiliary surgery. Receiver-operating characteristic curve analysis
      revealed that the predictive power of TBA was superior to that of the d-Bil/s-Bil
      ratio throughout the postoperative period, and that the TBA on postoperative day
      (POD) 1 showed the highest discriminatory power in the training set (area under
      the curve, 0.789; cutoff value, 470 mg/day). The TBA on POD 1 also showed the
      highest predictive power for sBF formation in the validation set, with a
      sensitivity of 100%, specificity of 97.1%, and accuracy of 97.1%. In conclusion,
      TBA may be a more reliable predictor of sBF than the conventionally used d-Bil/s
      Bil ratio. Early prediction of sBF may be useful for early removal of unnecessary
      prophylactic drainage tubes after hepatobiliary surgery.

PMID- 29070761
TI  - Price adjustment for traditional Chinese medicine procedures: Based on a
      standardized value parity model.
AB  - Traditional Chinese medicine (TCM) is an important part of China's medical
      system. Due to the prolonged low price of TCM procedures and the lack of an
      effective mechanism for dynamic price adjustment, the development of TCM has
      markedly lagged behind Western medicine. The World Health Organization (WHO) has
      emphasized the need to enhance the development of alternative and traditional
      medicine when creating national health care systems. The establishment of
      scientific and appropriate mechanisms to adjust the price of medical procedures
      in TCM is crucial to promoting the development of TCM. This study has examined
      incorporating value indicators and data on basic manpower expended, time spent,
      technical difficulty, and the degree of risk in the latest standards for the
      price of medical procedures in China, and this study also offers a price
      adjustment model with the relative price ratio as a key index. This study
      examined 144 TCM procedures and found that prices of TCM procedures were mainly
      based on the value of medical care provided; on average, medical care provided
      accounted for 89% of the price. Current price levels were generally low and the
      current price accounted for 56% of the standardized value of a procedure, on
      average. Current price levels accounted for a markedly lower standardized value
      of acupuncture, moxibustion, special treatment with TCM, and comprehensive TCM
      procedures. This study selected a total of 79 procedures and adjusted them by
      priority. The relationship between the price of TCM procedures and the suggested
      price was significantly optimized (p < 0.01). This study suggests that adjustment
      of the price of medical procedures based on a standardized value parity model is
      a scientific and suitable method of price adjustment that can serve as a
      reference for other provinces and municipalities in China and other countries and
      regions that mainly have fee-for-service (FFS) medical care.

PMID- 29070760
TI  - Induction of apoptosis by ethanol extract of Citrus unshiu Markovich peel in
      human bladder cancer T24 cells through ROS-mediated inactivation of the PI3K/Akt
      pathway.
AB  - Citrus unshiu peel has been used to prevent and treat various diseases in
      traditional East-Asian medicine including in Korea. Extracts of C. unshiu peel
      are known to have various pharmacological effects including antioxidant, anti
      inflammatory, and antibacterial properties. Although the possibility of their
      anti-cancer activity has recently been reported, the exact mechanisms in human
      cancer cells have not been sufficiently studied. In this study, the inhibitory
      effect of ethanol extract of C. unshiu peel (EECU) on the growth of human bladder
      cancer T24 cells was evaluated and the underlying mechanism was investigated. The
      present study demonstrated that the suppression of T24 cell viability by EECU is
      associated with apoptosis induction. EECU-induced apoptosis was found to
      correlate with an activation of caspase-8, -9, and -3 in concomitance with a
      decrease in the expression of the inhibitor of apoptosis family of proteins and
      an increase in the Bax:Bcl-2 ratio accompanied by the proteolytic degradation of
      poly(ADP-ribose) polymerase. EECU also increased the generation of reactive
      oxygen species (ROS), collapse of mitochondrial membrane potential, and
      cytochrome c release to the cytosol, along with a truncation of Bid. In addition,
      EECU inactivated phosphatidylinositol 3-kinase (PI3K) as well as Akt, a
      downstream molecular target of PI3K, and LY294002, a specific PI3K inhibitor
      significantly enhanced EECU-induced apoptosis and cell viability reduction.
      However, N-acetyl cysteine, a general ROS scavenger, completely reversed the EECU
      induced dephosphorylation of PI3K and Akt, as well as cell apoptosis. Taken
      together, these findings suggest that EECU inhibits T24 cell proliferation by
      activating intrinsic and extrinsic apoptosis pathways through a ROS-mediated
      inactivation of the PI3K/Akt pathway.

PMID- 29070762
TI  - A comparative study on predicting influenza outbreaks.
AB  - Worldwide, influenza is estimated to result in approximately 3 to 5 million
      annual cases of severe illness and approximately 250,000 to 500,000 deaths. We
      need an accurate time-series model to predict the number of influenza patients.
      Although time-series models with different time lags as feature spaces could lead
      to varied accuracy, past studies simply adopted a time lag in their models
      without comparing or selecting an appropriate number of time lags. We
      investigated the performance of adopting 6 different time lags in 6 different
      models: Auto-Regressive Integrated Moving Average (ARIMA), Support Vector
      Regression (SVR), Random Forest (RF), Gradient Boosting (GB), Artificial Neural
      Network (ANN), and Long Short Term Memory (LSTM) with hyperparameter adjustment.
      To the best of our knowledge, this is the first time that LSTM has been used to
      predict influenza outbreaks. As a result, we found that the time lag of 52 weeks
      led to the lowest Mean Absolute Percentage Error (MAPE) in the ARIMA, ANN and
      LSTM, while the machine learning models (SVR, RF, GB) achieved the lowest MAPEs
      with a time lag of 4 weeks. We also found that the MAPEs of the machine learning
      models were less than ARIMA, and the MAPEs of the deep learning models (ANN,
      LSTM) were less than those of the machine learning models. In all the models, the
      LSTM model of 4 layers reached the lowest MAPE of 5.4%, and the LSTM model of 5
      layers with regularization reached the lowest root mean squared error (RMSE) of
      0.00210.

PMID- 29070763
TI  - The synergic effect of BRAFV600E mutation and multifocality on central lymph node
      metastasis in unilateral papillary thyroid carcinoma.
AB  - The purpose of this study is to evaluate the potential synergic effect of
      BRAFV600E mutation and multifocality on central lymph nodes metastasis (CLNM) in
      the patients with unilateral papillary thyroid carcinoma (PTC). We enrolled 413
      patients with unilateral PTCs who accepted prophylactic unilateral or bilateral
      central lymph node dissection (LND). Univariate and multivariate analyses were
      made to determine the association between related factors and CLNM. Then, all
      patients were divided into 4 groups based on their status of BRAFV600E mutation
      and multifocality. Relative excess risk of interaction (RERI), attributable
      proportion (AP) of interaction and synergy index (SI) were applied to evaluate
      the interactive effect of these two factors on CLNM. Results showed that
      BRAFV600E mutation and multifocality were independent risk factors for CLNM. A
      further study revealed that unilateral PTCs accompanying multifocality with
      BRAFV600E mutation had the highest incidence of CLNM compared with other
      subgroups. Besides, RERI was 4.323 (95% CI = 1.276-7.369), AP was 0.523 (95% CI =
      0.364-0.682) and SI was 2.469 (95% CI = 1.607 to 3.794), indicating a significant
      additive interaction of BRAFV600E mutation and multifocality on CLNM. The present
      study has confirmed that BRAFV600E mutation and multifocality are risk factors
      for CLNM in unilateral PTC. Additionally, unilateral PTC patients accompanying
      multifocality with BRAFV600E mutation may have an increased risk of CLNM in
      clinically negative CLNM.

PMID- 29070764
TI  - Plasma lead, silicon and titanium concentrations are considerably higher in green
      sea turtle from the suburban coast than in those from the rural coast in Okinawa,
      Japan.
AB  - The purpose of this study was to compare the concentration of trace elements in
      the plasma of sea turtles that inhabited the suburban (Okinawa Main Island, n=8)
      and the rural coast (Yaeyama Island, n=57) in Okinawa, Japan. Particle induced X
      ray emission allowed detection of 20 trace and major elements. The wild sea
      turtles in the suburban coast in Okinawa were found to have high concentrations
      of Pb, Si and Ti in the plasma when compared to the rural area but there were no
      significant changes in the Al, As and Hg concentrations. These results may help
      to suggest the status of some elements in a marine environment. Further,
      monitoring the plasma trace and major element status in sea turtles can be used
      as a bio-monitoring approach by which specific types of elements found here could
      indicate effects that are related to human activities.

PMID- 29070765
TI  - Morphometric analysis of growing tenocytes in the superficial digital flexor
      tendon of piglets.
AB  - The fine structures of different tendons in various animals at different ages
      have been studied extensively to reveal their arrangement and growth patterns.
      However, knowledge of the microstructures of the growing tenocytes in the tendons
      of piglets is still lacking. Thus, we performed the first morphometric analysis
      to describe the characteristics of tenocytes in the metacarpal superficial
      digital flexor tendon of 0-, 10- and 20-day-old piglets. In the present study,
      hydrochloric acid/collagenase digestion was applied to remove the interstitial
      connective tissue to obtain clear visualization of intact tenocytes and their
      cytoplasmic processes (Cp). Then, the morphometry of the tenocytes was
      investigated by optical and electron microscopy. The mean +/- SE values of the
      fascicle area, number of tenocytes/fascicle, cell density, number of Cp/tenocyte,
      length of Cp, and thickness of Cp were compared among the three age groups.
      Significant differences (judged at P<0.05) were found in almost all morphometric
      aspects among the age groups, except for the number of Cp/cell (P=0.545) and
      thickness of the Cp (P=0.105). A decrease of cell density corresponded with an
      increase in the length of the Cp, which were extended to connect either with the
      Cp of the other tenocytes or the surrounding endotendineum. Moreover, an increase
      of the fascicle area reflected the increase in tendon diameter. The revealed
      morphometric characteristics are thus the outcome of tendon growth.

PMID- 29070766
TI  - Relationship between the side of pregnancy and side of subsequent ovarian
      activity during the early postpartum period in lactating dairy cows.
AB  - After parturition, the ovary ipsilateral to the side of previous pregnancy
      exhibits lower functional activity than that exhibited by the contralateral
      ovary. The local inhibitory effects of the corpus luteum of the previous
      pregnancy, and/or the presence of a previous gravid uterine horn, may induce the
      ipsilateral suppression of folliculogenesis. We examined the influence of the
      side of previous pregnancy on ovulation and folliculogenesis, until completion of
      the third postpartum ovulation. The ovaries of 30 Holstein cows were scanned by
      ultrasonography, through the three postpartum ovulation sequences. No significant
      differences in the development of growing follicles, 5-8 mm in diameter, were
      detected between ipsilateral and contralateral ovaries. However, the total number
      of dominant follicles emerging ipsilaterally before the second postpartum
      ovulation were less than those emerging contralaterally (25 vs. 75%), and both
      the first and second ovulation occurred less frequently on the ipsilateral versus
      contralateral side (23 vs. 77% and 27 vs. 73%, respectively). Sequential
      observation in this study clearly indicated that the influence of the side of
      previous pregnancy persisted until the second postpartum ovulation, and this
      affected postpartum dominant follicle selection and ovulation, but not the
      development of growing follicles.

PMID- 29070767
TI  - Genotoxic effects of occupational exposure to benzene in gasoline station
      workers.
AB  - Benzene, a hazardous component of gasoline, is a genotoxic class I human
      carcinogen. This study evaluated the genotoxic effects of occupational exposure
      to benzene in gasoline stations. Genotoxicity of exposure to benzene was assessed
      in peripheral blood leucocytes of 62 gasoline station workers and compared with
      an equal numbers of matched controls using total genomic DNA fragmentation,
      micronucleus test and cell viability test. An ambient air samples were collected
      and analyzed for Monitoring of benzene, toluene, ethyl benzene and xylene (BTEX)
      in work environment and control areas. DNA fragmentation, micronucleus and dead
      cells percent were significantly higher in exposed workers than controls. Level
      of benzene, Toluene, Ethyl benzene and xylene in the work environment were higher
      than the control areas and the permissible limits. Gasoline station workers
      occupationally exposed to benzene are susceptible to genotoxic effects indicated
      by increased DNA fragmentation, higher frequency of micronucleus and decreased
      leukocytes viability.

PMID- 29070768
TI  - Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen
      metabolites and endothelial function in Japanese patients: The GREAT clinical
      study.
AB  - Patients with growth hormone deficiency (GHD) have an increased risk of
      atherosclerosis and vascular mortality. Evidence suggests that endothelial
      dysfunction is involved in all stages of atherogenesis. This study examined the
      effect of growth hormone (GH) replacement therapy on diacron-reactive oxygen
      metabolites (d-ROMs) and endothelial function in Japanese patients with GHD,
      using peripheral arterial tonometry. This was an open-label, prospective, case
      control study. Nine patients with GHD who had not previously received any GH
      replacement therapy were enrolled. The following parameters were evaluated at
      baseline (before treatment), and after 24 weeks of GH replacement therapy:
      endothelial function using the reactive hyperemia index (RHI; EndoPAT(r) system),
      d-ROMs, blood pressure, and fasting lipid levels. Plasma GH and insulin-like
      growth factor-1 (IGF-1) levels were measured at baseline and after 24 weeks of GH
      replacement therapy. We also enrolled eight controls with pituitary disease but
      no GH deficiency. Over 24 weeks of GH replacement therapy, the serum IGF-1 levels
      normalized with significant improvement in the RHI (from 1.65 +/- 0.33 to 1.92 +/
      0.26, p < 0.05) and decreased d-ROM levels (from 356.8 +/- 64.1 to 303.1 +/-
      43.3 U.CARR, p < 0.05). There were no significant improvements in the RHI or d
      ROM levels in controls. GH replacement therapy in Japanese patients with GHD may
      be mediated by the reduced oxidative stress and the d-ROMs associated with the
      treatment.

PMID- 29070769
TI  - [Examination of factors for promoting cooperation using documents between
      occupational health physicians and psychiatrists].
AB  - OBJECTIVES: There is little specific information concerning the method and the
      efficacy of sharing information between occupational health physicians and
      psychiatrists regarding the employment status and medical history of their
      patients with mental illnesses. To promote cooperation between occupational
      health physicians and psychiatrists, we examined the points necessary to be
      included on medical information request forms exchanged between them. METHODS: We
      conducted focused group discussion (FGD) to identify the points that need to be
      described on the request form and the concerns in cooperation between
      occupational health physicians and psychiatrists. We conducted FGDs twice, with
      two different groups of nine psychiatrists participating in each round. We
      extracted and organized FGD results and determined the necessary request form
      points. Next, we assumed two different cases of workers with mental illnesses and
      created three request form templates with differing item descriptions and
      lengths. We also conducted a questionnaire survey among clinical psychiatrists to
      determine their impression of the templates. We performed logistic regression
      analysis on the obtained results. RESULTS: On the basis of the FGD results we
      extracted the situation in the workplace, clarification of points to be
      confirmed, representation of the occupational health physician's position, and
      handling of information provided by the doctor as points required for the request
      form. On the basis of these results and the opinions of occupational health
      specialists, we created a new request form using these points. Additionally, the
      results from the questionnaire survey about the prescribed items revealed the
      proportion of favorable answers regarding sufficient information written on the
      request form and a feeling of security for information provision increased (p <
      0.01). Conversely, the proportion of favorable responses for readability
      decreased. CONCLUSIONS: Psychiatrists are concerned about the possibility that
      their patient may be at a disadvantageous situation by providing their personal
      medical information and believe the clinical information required by the
      occupational health physicians is unclear. This suggests that there are factors
      impeding the cooperation between the occupational health physicians and
      psychiatrists. When an occupational health physician writes a request form,
      cooperation with psychiatrists may be promoted by enriching the request form
      contents and by including the representation of the occupational health
      physician's position and the intended purpose of the provided information by
      paying attention to the volume of sentences.

PMID- 29070770
TI  - Application of an enzyme-linked immunosorbent assay for detection of antibodies
      to Actinobacillus pleuropneumoniae serovar 15 in pig sera.
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) using lipopolysaccharide
      extract as antigen was evaluated for detection of antibodies to Actinobacillus
      pleuropneumoniae serovar 15. The serovar 15 ELISA had a higher sensitivity and
      specificity than latex agglutination test for 63 and 80 sera from pigs
      experimentally infected and not infected with A. pleuropneumoniae, respectively.
      When the serovar 15 ELISA was applied to 454 field sera, high rates of
      seropositivity were found in pigs from farms infected with A. pleuropneumoniae
      serovar 15, but not in those from farms free of A. pleuropneumoniae serovar 15.
      The results suggest that the serovar 15 ELISA may be useful for the serological
      surveillance of infection with A. pleuropneumoniae serovar 15.

PMID- 29070772
TI  - Coexisting Thymic and Pulmonary Carcinoid Tumors Associated with Multiple
      Endocrine Neoplasia Type1.
AB  - An anterior mediastinal tumor was detected in a 45-year-old female during a
      medical checkup. Chest computed tomography (CT) showed the anterior mediastinal
      tumor and a pulmonary tumor in the right lower lobe. Furthermore, tumors of the
      parathyroid gland, pancreas, and pituitary gland were also detected. She was
      clinically diagnosed with multiple endocrine neoplasia type1 (MEN1). The patient
      underwent extended thymectomy combined with mediastinal lymph node dissection and
      wedge resection of the lung including the right pulmonary lesion via a median
      sternotomy. We diagnosed the patient with an atypical carcinoid tumor of the
      thymus, a typical pulmonary carcinoid tumor.

PMID- 29070771
TI  - Imbalance of autonomic nervous systems involved in ventricular arrhythmia after
      splenectomy in dogs.
AB  - The role of cardiac autonomic modulation on ventricular arrhythmia, known as
      ventricular premature complexes (VPC), after splenectomy was investigated. Twelve
      dogs undergoing splenectomy were divided into 2 groups: low VPC (<1,000/day, n=6)
      and high VPC groups (>=1,000/day, n=6). Electrocardiograph recording was
      performed prior to (D0), during the first three days (D1-3) and on day 9 (D9)
      after surgery. Arrhythmic indices, Tpeak-Tend, corrected QT interval and short
      term variability of QT interval as well as heart rate variability (HRV) were
      evaluated. Plasma concentrations of norepinephrine (NE) and epinephrine (E) were
      measured. In the high VPC group, the occurrences of VPC were significantly
      increased (P<0.05) after surgery, and reached the levels higher than those in the
      low VPC group. For the arrhythmic indices, only Tp-Te in the high VPC group
      increased significantly (P<0.05) after surgery. For HRV analysis, enhancement of
      both time and frequency domains were found postoperatively in both groups. On D2,
      however, the high VPC group showed significantly lower total power and high
      frequency with higher low to high frequency ratio (P<0.05) than the low VPC
      group. Plasma NE concentration significantly increased in the high VPC group
      after surgery. Dogs in the high VPC group had shorter survival time than those in
      the low VPC group. In conclusion, dogs with imbalance cardiac autonomic
      modulation accompanied with high circulating NE concentration after splenectomy
      are prone to ventricular arrhythmia, which leads to short survival time.

PMID- 29070773
TI  - Determination of the Marker Diarylheptanoid Phytoestrogens in Curcuma comosa
      Rhizomes and Selected Herbal Medicinal Products by HPLC-DAD.
AB  - A method for quantification of diarylheptanoids in Curcuma comosa rhizomes and
      selected pharmaceutical preparations was established by using HPLC-diode array
      detector (DAD). The chromatographic separation of three diarylheptanoids [(3S)-1
      (3,4-dihydroxy-phenyl)-7-phenyl-(6E)-6-hepten-3-ol (1), (3R)-1,7-diphenyl-(4E,6E)
      4,6-heptadien-3-ol (2), and (3S)-1,7-diphenyl-(6E)-6-hepten-3-ol (3)] was
      performed on a Luna C18 analytical column using gradient elution with 0.5% acetic
      acid in water and acetonitrile with a flow rate of 1 mL/min and a column
      temperature of 35 degrees C. The calibration curves for the analytes showed good
      linearity (R2>0.999), high precision (relative standard deviation (RSD) <2%) and
      acceptable recovery (98.35-103.90%, RSD <2%). The limit of detection (LOD) and
      limit of quantification (LOQ) were 0.06-0.22 and 0.18-0.69 ug/mL, respectively.
      The results of all validated parameters were within the limits according to the
      International Conference on Harmonization (ICH) Guidelines. The established
      method was successfully applied for qualitative and quantitative determination of
      the three constituents in different samples of C. comosa and some commercial
      products in capsules. The simplicity, rapidity, and reliability of the method
      could be useful for the fingerprint analysis and standardization of
      diarylheptanoids, which are responsible for the estrogenic activity in raw
      materials and herbal medicinal products of C. comosa.

PMID- 29070774
TI  - Bone Marrow Endothelial Cells Induce Immature and Mature B Cell Egress in
      Response to Erythropoietin.
AB  - Bone marrow stromal cells, including endothelial cells and mesenchymal stromal
      cells, support the maintenance, differentiation, and retention of hematopoietic
      stem and precursor cells under steady state conditions. At the onset of an
      emergency, such as severe blood loss or infection, the status of hematopoiesis in
      the bone marrow changes rapidly to ensure efficient production of cells of
      specific lineages; however, the function of stromal cells in emergency
      hematopoiesis has not been fully elucidated. Here, we unexpectedly found that B
      precursor, mature B, and T cells were released from the bone marrow into the
      blood circulation in the early phase of hemorrhagic anemia and phenylhydrazine
      induced hemolytic anemia. Administration of erythropoietin, which normally
      increases in response to anemia, stimulated the egress of IgDlow immature B cells
      and recirculating mature B cells, which usually reside in the perivascular and
      intravascular space, from the bone marrow within 24 h. We also observed that
      endothelial cells in the bone marrow expressed erythropoietin receptor, and the
      expression levels were higher than those in other tissues. Erythropoietin
      stimulation of bone marrow endothelial cells induced the phosphorylation of STAT5
      in vitro. Moreover, in vivo treatment with erythropoietin decreased surface VCAM1
      expression and Cxcl12 transcription in bone marrow endothelial cells, both of
      which are essential for immature and mature B cell retention in the bone marrow.
      These results suggest that bone marrow endothelial cells can sense and rapidly
      respond to erythropoietin increase during anemia, thereby regulating B cell
      emigration from the bone marrow during emergency hematopoiesis.Key words:
      erythropoietin, anemia, endothelial cells, B cell, bone marrow microenvironment.

PMID- 29070775
TI  - Expression of Ror2 Associated with Fibrosis of the Submandibular Gland.
AB  - The submandibular gland (SMG) is one of the major salivary glands that play
      important roles for variety of physiological functions, such as digestion of
      foods, prevention of infection, and lubrication of the mouth. Dysfunction of the
      SMG, often associated with a salivary inflammation, adversely influences a
      person's quality of life. However, the mechanism underlying inflammation-driven
      dysfunction of the SMG is largely unknown. Here, we used a mouse model in which
      the main excretory duct of the SMG is ligated unilaterally to induce inflammation
      of the gland and examined the expression of Wnt5a, Ror1 and Ror2 genes, encoding
      Wnt5a ligand and its cognate receptors, which have been implicated in tissue
      damage or inflammatory responses in variety of tissues. We show that expression
      levels of Ror1, Ror2, and Wnt5a are increased in the ligated SMG undergoing
      interstitial fibrosis, which is accompanied by robust expression of fibrosis
      associated genes, such as TGF-beta1, TNF-alpha, IL-1beta, and MMP-2. Increased
      immunostaining signal of Ror2 was detected in the fibrotic tissues with abundant
      accumulation of fibroblasts and collagen fibers in the ligated SMG, suggesting
      that Ror2-mediated signaling might be activated in response to tissue damage and
      associated with progression of fibrosis in the SMG.Key words: submandibular
      gland, Ror2, Wnt5a, fibrosis, inflammation.

PMID- 29070777
TI  - Calcification in rat developing mandibular bone demonstrated by whole mount
      staining, microcomputed tomography and scanning electron microscopy with energy
      dispersive X-ray spectroscopy.
AB  - The study was designed to investigate calcification in developing rat mandibular
      bone using whole mount staining, micro-computed tomography (micro-CT) and
      scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX).
      Wistar rats at embryonic days 16, 18, and 20 and postnatal weeks 1 and 6 were
      used. Rats were fixed with 4% paraformaldehyde and heads were resected, frozen
      and sectioned for histology, then analysed with SEM-EDX. Some of the specimens
      were observed with micro-CT. Other rats were fixed and stained with alcian blue
      and alizarin red for whole mount staining. Histology and whole mount staining
      showed that osteoid was deposited around Meckel's cartilage at day 15 and
      developed into bone at day 16. Accumulation of Ca and P was identified in the
      bone matrix with SEM-EDX. The area of bone expanded until week 6. The Ca/P ratio
      increased, whereas the C/Ca and C/P ratios decreased during development. Micro-CT
      demonstrated an increase in radio-opacity with bone development. The results
      suggest that rat mandibular bone formation is initiated around Meckel's cartilage
      at day 15. Deposition and maturation of the calcium phosphate mineral increase
      gradually with decrease in the organic component as the rat mandible develops.

PMID- 29070776
TI  - CCL5 is induced by TLR 3 signaling in HuCCT1 human biliary epithelial cells:
      possible involvement in the pathogenesis of biliary atresia.
AB  - Biliary atresia (BA) is a disease of the newborn that is characterized by
      progressive, inflammatory and sclerosing cholangiopathy. Innate immune responses
      to viral components are thought to be involved in the pathogenesis of BA. It is
      also reported that some chemokines, such as CCL5, are possibly involved in the
      pathogenesis of experimental animal model of BA. We treated human biliary
      epithelial HuCCT1 cells with polyinosinic-polycytidylic acid (poly IC), an
      authentic double-stranded RNA (dsRNA) which mimics viral RNA, and analyzed the
      CCL5 expression by quantitative reverse transcription-PCR (qRT-PCR) and enzyme
      linked immunosorbent assay (ELISA). To examine the regulation mechanisms of CCL5,
      we subjected the cells to RNA interference (siRNA) against Toll-like receptor 3
      (TLR3), interferon (IFN)-beta, NF-kappaB p65 and IFN regulatory factor (IRF) 3.
      Immunohistochemical staining for CCL5 was also performed in tissues from patients
      with BA. Poly IC induced CCL5 expression in HuCCT1 cells. CCL5 expression induced
      by poly IC was inhibited by the knockdown of TLR3, p65 or IRF3, but it was not
      affected by knockdown of IFN-beta. Immunohistochemical staining showed that CCL5
      was strongly expressed in biliary epithelial cells of patients with BA. The
      current study suggests that TLR3 signaling induces CCL5 expression via NF-kappaB
      and IRF3 in bile duct cells, and this pathway may be involved in the pathogenesis
      of BA.

PMID- 29070778
TI  - Integrative method for three-dimensional imaging of the entire Golgi apparatus by
      combining thiamine pyrophosphatase cytochemistry and array tomography using
      backscattered electron-mode scanning electron microscopy.
AB  - Thiamine pyrophosphatase (TPPase) cytochemistry is an established method for
      specific labeling of the trans-Golgi cisterns in tissue sections. Herein, we
      combined this enzyme cytochemical method with array tomography using scanning
      electron microscopy (SEM), a new imaging technique based on collection of
      backscattered electron (BSE) images of consecutive resin-embedded sections on
      glass slides, to detect the entire three-dimensional (3D) organization of the
      Golgi apparatus with sufficient spatial resolution. As the signal intensity of
      BSE depends on the atomic number of the materials, lead precipitates confined to
      the trans-Golgi cisterns after TPPase cytochemistry were clearly observed by BSE
      mode SEM. The mild fixative used for TPPase cytochemistry also enabled accurate
      identification of target gonadotropes in the composite pituitary tissue by
      immunocytochemical staining. By 3D reconstruction of the entire trans-Golgi
      cisterns based on serial ultrathin section images of tissues after TPPase
      cytochemistry, we detected ultrastructural differences in the 3D configuration of
      the Golgi apparatus between cerebellar Purkinje cells and pituitary gonadotropes.
      The appropriate combination of enzyme cytochemistry and/or immunostaining with
      array tomography will further clarify the relationship between the organization
      and functional states of the Golgi apparatus.

PMID- 29070779
TI  - Effects of the antiepileptic drugs topiramate and lamotrigine on bone metabolism
      in rats.
AB  - Long-term treatment with antiepileptic drugs (AED) is associated with an elevated
      risk of bone fracture due to decreased bone mineral density (BMD). Phenytoin has
      been shown to affect bone metabolism adversely, whereas newly developed AEDs have
      not been studied. This study evaluated the effects of topiramate and lamotrigine
      on bone metabolism in rats. Five-week-old male Sprague-Dawley rats were treated
      orally with phenytoin (20 mg/kg), topiramate (5 or 20 mg/kg), or lamotrigine (2
      or 10 mg/kg) daily for 12 weeks. Phenytoin reduced bone strength, measured by
      maximum load to failure of the femoral mid-diaphysis, along with reduced femur
      total BMD. Serum tartrate-resistant acid phosphatase-5b levels significantly
      increased after phenytoin treatment, while serum osteocalcin levels decreased
      after topiramate 20 mg/kg treatment. Furthermore, osteoblast surface and bone
      mineralizing surface were significantly lowered by topiramate. Lamotrigine
      treatment did not affect bone strength, BMD, or bone turnover. We demonstrated
      that phenytoin treatment significantly increased bone resorption and lowered BMD
      and bone strength. Since lamotrigine did not affect bone metabolism, it can be
      concluded that lamotrigine is safety medicine for bone health. Topiramate was
      associated with decreased bone formation, which may affect bone strength and BMD
      with chronic use. Thus, patients taking topiramate should be monitored for
      changes in BMD to avoid risk of fracture.

PMID- 29070780
TI  - No change in the prevalence of latent prostate cancer over the last 10 years: a
      forensic autopsy study in Japan.
AB  - Although the morbidity rate of prostate cancer has increased with 2.3 times in
      these 10 years in Japan, little is known about the changes in the prevalence of
      latent prostate cancer. To understand changes in the prevalence of latent
      prostate cancer, a retrospective analysis was performed. Forensic autopsy
      findings from Tochigi Prefecture between September 2012 and February 2014 were
      collected. Two cross sections, from the base and apex of the prostate, were
      examined histopathologically. The prevalence of latent prostate cancer was
      compared with findings from forensic autopsies performed between August 2002 and
      July 2005 in the same region. The prevalence of latent prostate cancer in both
      groups was similar, showing an overall prevalence of 13.6% and 12.2% and a
      Gleason score >6 of 6.2% and 7.1%, respectively. When prevalence was compared by
      cause of death, the values were similar for both groups. The prevalence of latent
      prostate cancer in this Japanese population did not show any significant change
      over the past 10 years. The dramatic increase in morbidity rate for prostate
      cancer could be from the increase in prostate-specific antigen screening and
      subsequent referral to urologists.

PMID- 29070781
TI  - Cordycepin induces apoptotic cell death and inhibits cell migration in renal cell
      carcinoma via regulation of microRNA-21 and PTEN phosphatase.
AB  - Cordycepin is an active component extracted from Traditional Chinese medical herb
      Cordyceps militaris. Many reports demonstrated that cordycepin harbors antitumor
      activity in a broad spectrum of cancer types. In this study the actions and the
      underneath molecular mechanisms of cordycepin were investigated in renal cell
      carcinoma Caki-1 cell line. Results showed that cordycepin induced apoptotic cell
      death and inhibited cell migration in Caki-1 cells. Quantitative real-time PCR
      results and western blot analyses indicated cordycepin dose-dependently decreased
      microRNA-21 expression and Akt phosphorylation levels in Caki-1 cells, but
      increased PTEN phosphatase levels. Block of cordycepin-induced microRNA-21
      decrease or PTEN increase in Caki-1 cells by transfection of microRNA-21 mimic or
      PTEN siRNA significantly attenuated cordycepin-induced cell death and inhibition
      of cell migration. Taken together, findings in present study suggested that
      cordycepin induced apoptotic cell death in renal cell carcinoma through
      regulation of microRNA-21 and PTEN phosphatase. Furthermore, present study also
      firstly illustrated that cordycepin inhibited cell migration of renal cell
      carcinoma, which also involved microRNA-21 and PTEN phosphatase.

PMID- 29070783
TI  - ?

PMID- 29070782
TI  - Temporal Patterns of Individual Neuronal Firing in Rat Dorsal Column Nuclei
      Provide Information Required for Somatosensory Discrimination.
AB  - A wealth of mechanical information from the body generates various forms of
      sensory experience during touch or kinesthesia. Dorsal column nuclei (DCN) in the
      medulla are the first relay station for somatosensory inputs from peripheral
      receptors. These nuclei integrate somatosensory information and send the output
      to higher-order centers; therefore, investigating the firing patterns of DCN
      neurons should elucidate coding principles within the somatosensory system. In
      this study, we quantified the firing patterns of DCN neurons and examined whether
      the firing patterns of particular neurons are altered when moving tactile stimuli
      are applied in different directions. The activities of 17 neurons in the DCN of
      anesthetized rats were selected and their firing patterns were analyzed using
      LvR, which refers to the local variation of intervals of action potentials (i.e.,
      the cross-correlation between consecutive intervals of action potentials)
      compensated by the refractoriness constant, R. The LvR of the 17 neurons ranged
      widely from 0.35 to 2.28. Of the 17 neurons, 12 responded to hair deflection
      (hair neurons), whereas five responded specifically to movement of forelimb
      joints. In 11 of 12 hair neurons, moving stimuli were applied in two to four
      different directions, which yielded 25 pairs of comparisons. Of these, 14 pairs
      (56%) showed significant differences in LvR. Among these 14 pairs, the range of
      LvR fluctuation was 0.13 +/- 0.06 (mean +/- standard deviation) and its effect
      size (Cohen's d) was 0.6 +/- 0.2. These results suggest that the firing pattern
      of individual DCN neurons may contribute to somatosensory discrimination.

PMID- 29070785
TI  - Asymptomatic Meningitis and Lung Cavity in a Case of Cryptococcosis.
AB  - BACKGROUND Cryptococcus neoformans (C. neoformans) infection is one of the most
      common opportunistic infections in AIDS patients. C. neoformans usually infects
      the central nervous system (CNS) and/or lungs with typical clinical
      manifestation. CASE REPORT Here, we report the case of a 52-year-old HIV-1
      infected man with disseminated cryptococcosis, including subacute meningitis,
      pulmonary, and cutaneous cryptococcosis, but only skin lesion served as the chief
      complaint. Moreover, the results of cerebrospinal fluid (CSF) tests and lung
      computed tomography (CT) scan were atypical. CONCLUSIONS We present the clinical
      characteristics of this case and discuss the diagnostic procedure, which will
      likely help clinicians in making a timely definitive diagnosis of this disease.

PMID- 29070784
TI  - Kaempferol Sensitizes Human Ovarian Cancer Cells-OVCAR-3 and SKOV-3 to Tumor
      Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis via
      JNK/ERK-CHOP Pathway and Up-Regulation of Death Receptors 4 and 5.
AB  - BACKGROUND Ovarian cancer is the most common gynecological malignancies in women,
      with high mortality rates worldwide. Tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF)
      superfamily which preferentially induces apoptosis of cancer cells. However,
      acquired resistance to TRAIL hampers its therapeutic application. Identification
      of compounds that sensitize cancer cells to TRAIL is vital in combating
      resistance to TRAIL. The effect of kaempferol, a flavonoid enhancing TRAIL
      induced apoptosis in ovarian cancer cells, was investigated in this study.
      MATERIAL AND METHODS The cytotoxic effects of TRAIL (25 ng/mL) and kaempferol (20
      100 uM) on human ovarian cancer cells OVCAR-3 and SKOV-3 were assessed. Effect of
      kaempferol on the expression patterns of cell survival proteins (Bcl-xL, Bcl-2,
      survivin, XIAP, c-FLIP) and apoptotic proteins (caspase-3, caspase-8, caspase-9,
      Bax) were studied. The influence of kaempferol on expression of DR4 and DR5 death
      receptors on the cell surface and protein and mRNA levels was also analyzed.
      Apoptosis following silencing of DR5 and CHOP by small interfering RNA (siRNA),
      and activation of MAP kinases were analyzed as well. RESULTS Kaempferol enhanced
      apoptosis and drastically up-regulated DR4, DR5, CHOP, JNK, ERK1/2, p38 and
      apoptotic protein expression with decline in the expression of anti-apoptotic
      proteins. Further transfection with siRNA specific to CHOP and DR5 indicated the
      involvement of CHOP in DR5 up-regulation and also the contribution of DR5 in
      kaempferol-enhanced TRAIL-induced apoptosis. CONCLUSIONS Kaempferol sensitized
      ovarian cancer cells to TRAIL-induced apoptosis via up-regulation of DR4 and DR5
      through ERK/JNK/CHOP pathways.

PMID- 29070786
TI  - Binding patterns of homo-peptides on bare magnetic nanoparticles: insights into
      environmental dependence.
AB  - Magnetic nanoparticles (MNP) are intensively investigated for applications in
      nanomedicine, catalysis and biotechnology, where their interaction with peptides
      and proteins plays an important role. However, the characterisation of the
      interaction of individual amino acids with MNP remains challenging. Here, we
      classify the affinity of 20 amino acid homo-hexamers to unmodified iron oxide
      nanoparticles using peptide arrays in a variety of conditions as a basis to
      identify and rationally design selectively binding peptides. The choice of buffer
      system is shown to strongly influence the availability of peptide binding sites
      on the MNP surface. We find that under certain buffer conditions peptides of
      different charges can bind the MNP and that the relative strength of the
      interactions can be modulated by changing the buffer. We further present a model
      for the competition between the buffer and the MNP's electrostatically binding to
      the adsorption sites. Thereby, we demonstrate that the charge distribution on the
      surface can be used to correlate the binding of positively and negatively charged
      peptides to the MNP. This analysis enables us to engineer the binding of MNP on
      peptides and contribute to better understand the bio-nano interactions, a step
      towards the design of affinity tags for advanced biomaterials.

PMID- 29070787
TI  - Transcriptomic response to thermal and salinity stress in introduced and native
      sympatric Palaemon caridean shrimps.
AB  - Organisms develop local adaptations to cope with spatially and temporally
      variable environments such as estuarine habitats, where abiotic parameters such
      as salinity and temperature fluctuate continuously. Studying the regulation of
      gene expression in a variable environment allows us to understand the underlying
      molecular mechanisms of these adaptations and the relative roles of the genetic
      and plastic response. The transcriptomes of the European native Palaemon
      longirostris (PL) and the introduced P. macrodactylus (PM) shrimps are described
      and compared after an experiment simulating summer conditions in the Guadalquivir
      Estuary, Spain. Specimens, collected in the Guadalquivir Estuary, were maintained
      at a temperature and salinity of 20  degrees C and 5 ppt for the control, and 30 
      degrees C and 15 ppt for the stress treatment. A large amount of differential
      gene expression was observed: 16,013 and 2,594 for PL and PM respectively.
      Functionally annotated unigenes revealed some differences, with PL seemingly
      having to face stronger physiological stress than PM. Thus, PM seems to have
      greater resistance than PL under conditions of high temperature and salinity.
      These results constitute a step forward in the understanding of the underlying
      molecular mechanisms of genetic adaptation of native invertebrates, and alien
      taxa that have successfully invaded estuaries in temperate regions around the
      world.

PMID- 29070788
TI  - Pharmacological inhibition of myostatin improves skeletal muscle mass and
      function in a mouse model of stroke.
AB  - In stroke patients, loss of skeletal muscle mass leads to prolonged weakness and
      less efficient rehabilitation. We previously showed that expression of myostatin,
      a master negative regulator of skeletal muscle mass, was strongly increased in
      skeletal muscle in a mouse model of stroke. We therefore tested the hypothesis
      that myostatin inhibition would improve recovery of skeletal muscle mass and
      function after cerebral ischemia. Cerebral ischemia (45 minutes) was induced by
      intraluminal right middle cerebral artery occlusion (MCAO). Swiss male mice were
      randomly assigned to Sham-operated mice (n = 10), MCAO mice receiving the vehicle
      (n = 15) and MCAO mice receiving an anti-myostatin PINTA745 (n = 12; subcutaneous
      injection of 7.5 mg.kg-1 PINTA745 immediately after surgery, 3, 7 and 10 days
      after MCAO). PINTA745 reduced body weight loss and improved body weight recovery
      after cerebral ischemia, as well as muscle strength and motor function. PINTA745
      also increased muscle weight recovery 15 days after cerebral ischemia.
      Mechanistically, the better recovery of skeletal muscle mass in PINTA745-MCAO
      mice involved an increased expression of genes encoding myofibrillar proteins.
      Therefore, an anti-myostatin strategy can improve skeletal muscle recovery after
      cerebral ischemia and may thus represent an interesting strategy to combat
      skeletal muscle loss and weakness in stroke patients.

PMID- 29070789
TI  - The electrophysiological connectome is maintained in healthy elders: a power
      envelope correlation MEG study.
AB  - Functional magnetic resonance imaging (fMRI) studies report age-related changes
      in resting-state functional connectivity (rsFC), suggesting altered or
      reorganized connectivity patterns with age. However, age-related changes in
      neurovascular coupling might also partially account for altered connectivity
      patterns. Here, we used resting-state magnetoencephalography (MEG) and a
      connectome approach in carefully selected healthy young adults and elders. The
      MEG connectome was estimated as rsFC matrices involving forty nodes from six
      major  resting-state networks. Source-level rsFC maps were computed in relevant
      frequency bands using leakage-corrected envelope correlations. Group differences
      were statistically assessed using non-parametric permutation tests. Our results
      failed to evidence significant age-related differences after correction for
      multiple comparisons in the alpha and the beta bands both for static and dynamic
      rsFC, suggesting that the electrophysiological connectome is maintained in
      healthy ageing. Further studies should compare the evolution of the human brain
      connectome as estimated using fMRI and MEG in same healthy young and elder
      adults, as well as in ageing conditions associated with cognitive decline. At
      present, our results are in agreement with the brain maintenance theory for
      successful aging as they suggest that preserved intrinsic functional brain
      integration contributes to preserved cognitive functioning in healthy elders.

PMID- 29070791
TI  - Identification of molecular alterations in leukocytes from gene expression
      profiles of peripheral whole blood of Alzheimer's disease.
AB  - Blood-based test has been considered as a promising way to diagnose and study
      Alzheimer's disease (AD). However, the changed proportions of the leukocytes
      under disease states could confound the aberrant expression signals observed in
      mixed-cell blood samples. We have previously proposed a method, Ref-REO, to
      detect the leukocyte specific expression alterations from mixed-cell blood
      samples. In this study, by applying Ref-REO, we detect 42 and 45 differentially
      expressed genes (DEGs) between AD and normal peripheral whole blood (PWB) samples
      in two datasets, respectively. These DEGs are mainly associated with AD
      associated functions such as Wnt signaling pathways and mitochondrion
      dysfunctions. They are also reproducible in AD brain tissue, and tend to interact
      with the reported AD-associated biomarkers and overlap with targets of AD
      associated PWB miRNAs. Moreover, they are closely associated with aging and have
      severer expression alterations in the younger adults with AD. Finally, diagnostic
      signatures are constructed from these leukocyte specific alterations, whose area
      under the curve (AUC) for predicting AD is higher than 0.73 in the two AD PWB
      datasets. In conclusion, gene expression alterations in leukocytes could be
      extracted from AD PWB samples, which are closely associated with AD progression,
      and used as a diagnostic signature of AD.

PMID- 29070793
TI  - Cellular splicing factor UAP56 stimulates trimeric NP formation for assembly of
      functional influenza viral ribonucleoprotein complexes.
AB  - The influenza virus RNA genome exists as a ribonucleoprotein (RNP) complex by
      interacting with NP, one of virus-encoded RNA binding proteins. It is proposed
      that trimeric NP is a functional form, but it is not clear how trimeric NP is
      formed and transferred to RNA. UAP56, a cellular splicing factor, functions as a
      molecular chaperone for NP and is required for the replication-coupled RNP
      formation of newly synthesized viral genome, but the details of NP transfer to
      viral RNA by UAP56 is unclear. Here we found that UAP56 is complexed with
      trimeric NP, but not monomeric NP. Gel filtration analysis and atomic force
      microscopy analysis indicated that the complex consists of two trimeric NP
      connected by UAP56. We also found that UAP56 stimulates trimeric NP formation
      from monomeric NP even at physiological salt concentrations. Thus, UAP56
      facilitates the transfer of NP to viral RNA since trimeric NP has higher RNA
      binding activity than monomeric NP. Further, UAP56 represses the binding of
      excess amount of NP to RNA possibly by transferring trimeric NP. Collectively, we
      propose that UAP56 stimulates viral RNP formation through promotion of the
      assembly of trimeric NP and is important for the structural integrity of NP-RNA
      complex.

PMID- 29070792
TI  - miR-204 is associated with an endocrine phenotype in human pancreatic islets but
      does not regulate the insulin mRNA through MAFA.
AB  - miR-204 has been proposed to modulate insulin expression in human pancreatic
      islets by regulating the expression of the MAFA transcript, and in turn insulin
      transcription. We investigated miR-204 expression in pancreatic endocrine tumors
      (PET), a panel of human tissues, tissues derived from pancreatic islet
      purification, and in induced pluripotent stem cells (iPSCs) differentiated
      towards a pancreatic endocrine phenotype by quantitative real time RT-PCR or
      droplet digital PCR (ddPCR). In addition, we evaluated the effect of miR-204 up-
      or down-regulation in purified human islets and in the EndoC-betaH1 cell line, as
      an experimental model of human pancreatic beta cells. Our results confirm that
      miR-204 was enriched in insulin producing PET, in beta cells within healthy
      pancreatic islets, and highly expressed in EndoC-betaH1 cells. Moreover, in iPSCs
      miR-204 increased stepwise upon stimulated differentiation to insulin producing
      cells. However, up- or down-regulation of miR-204 in human islets and in EndoC
      betaH1 cells resulted in modest and not significant changes of the MAFA and INS
      mRNAs measured by ddPCR or c-peptide release. Our data confirm the association of
      miR-204 with a beta cell endocrine phenotype in human pancreatic islets, but do
      not support its direct role in regulating the levels of insulin mRNA through
      MAFA.

PMID- 29070794
TI  - Yucasin DF, a potent and persistent inhibitor of auxin biosynthesis in plants.
AB  - The plant hormone auxin plays a crucial role in plant growth and development.
      Indole-3-acetic acid (IAA), a natural auxin, is mainly biosynthesized by two
      sequential enzyme reactions catalyzed by TAA1 and YUCCA (YUC). TAA1 is involved
      in the conversion of tryptophan to IPA, and YUC catalyzes the conversion of IPA
      to IAA. We previously demonstrated that yucasin inhibits AtYUC1 enzyme activity
      and suppress high-auxin phenotype of YUC overexpression plants, although yucasin
      displayed weak effects on the auxin-related phenotype of wild-type plants. To
      develop more potent YUC inhibitors, various derivatives of yucasin were
      synthesized, and their structure-activity relationships were investigated.
      Yucasin difluorinated analog (YDF) (5-[2,6-difluorophenyl]-2,4-dihydro-[1,2,4]
      triazole-3-thione) was identified to be a more potent YUC inhibitor than the
      original yucasin. YDF caused an auxin-deficient phenotype in Arabidopsis wild
      type plants that was restored with auxin application. YDF was found to be highly
      stable regarding metabolic conversion in vivo, accounting for the potent activity
      of the inhibition of IAA biosynthesis in planta. Photoaffinity labeling
      experiments demonstrated that yucasin-type inhibitors bind to the active site of
      AtYUC1. YDF is a promising auxin biosynthesis inhibitor and is a useful chemical
      tool for plant biology and agrochemical studies.

PMID- 29070796
TI  - RNAi-mediated treatment of two vertically transmitted rhabdovirus infecting the
      salmon louse (Lepeophtheirus salmonis).
AB  - Rhabdoviruses are a family of enveloped negative-sense single-stranded RNA
      viruses infecting a variety of hosts. Recently, two vertically transmitted salmon
      louse (Lepeophtheirus salmonis) rhabdoviruses (LsRV) have been identified. The
      prevalence of these viruses was measured along the Norwegian coast and found to
      be close to 100%, and with the present lack of suitable cell lines to propagate
      these viruses, it is challenging to obtain material to study their host impact
      and infection routes. Thus, virus free lice strains were established from virus
      infected lice carrying one or both LsRVs by treating them with N protein dsRNA
      twice during development. The viral replication of the N protein was specifically
      down-regulated following introduction of virus-specific dsRNA, and virus-free
      lice strains were maintained for several generations. A preliminary study on
      infection routes suggested that the LsRV-No9 is maternally transmitted, and that
      the virus transmits from males to females horizontally. The ability to produce
      virus free strains allows for further studies on transmission modes and how these
      viruses influences on the L.salmonis interaction with its salmonid host.
      Moreover, this study provides a general fundament for future studies on how
      vertically transmitted rhabdoviruses influence the biology of their arthropod
      hosts.

PMID- 29070795
TI  - Ecobody technology: rapid monoclonal antibody screening method from single B
      cells using cell-free protein synthesis for antigen-binding fragment formation.
AB  - We report a rapid and cost-effective monoclonal antibody screening method from
      single animal B cells using reverse transcription (RT)-PCR and Escherichia coli
      cell-free protein synthesis (CFPS), which allows evaluation of antibodies within
      2 working days. This process is named "Ecobody technology". The method includes
      strategies to isolate B cells that specifically bind an antigen from the
      peripheral blood of immunised animals, and single-cell RT-PCR to generate DNA
      fragments of the VH and VL genes, followed by CFPS for production of fragments of
      antigen binding (Fab). In the CFPS step, we employed our techniques: 1) 'Zipbody'
      as a method for producing Fab, in which the association of heavy and light chains
      is facilitated by adhesive leucine zipper peptides fused at the C-termini of the
      Fab; and 2) an N-terminal SKIK peptide tag that can increase protein expression
      levels. Using Ecobody technology, we obtained highly-specific monoclonal
      antibodies for the antigens Vibrio parahaemolyticus and E. coli O26. The anti-V.
      parahaemolyticus Zipbody mAb was further produced in E. coli strain SHuffle T7
      Express in inclusion bodies and refolded by a conventional method, resulting in
      significant antigen-binding activity (K D = 469 pM) and productivity of 8.5 mg
      purified antibody/L-culture.

PMID- 29070797
TI  - Active Immunization Against hIAPP Oligomers Ameliorates the Diabetes- Associated
      Phenotype in a Transgenic Mice Model.
AB  - Type 2 diabetes is characterized by insulin tolerance in target cells followed by
      a reduction of pancreatic beta-cell mass. Islet amyloid polypeptide oligomeric
      assemblies were shown to contribute to beta-cell apoptosis by forming discrete
      pores that destabilize the cellular membrane. We previously characterized alpha
      helical cytotoxic islet amyloid polypeptide oligomers which interact with cell
      membranes, following a complete internalization that leads to cellular apoptosis.
      Moreover, antibodies which bind the oligomers and neutralize the cytotoxicity
      were exclusively identified in the serum of type 2 diabetes patients. Here, we
      examined the usage of the newly characterized oligomers as an active immunization
      agent targeting amyloid self- assembly in a diabetes-associated phenotype
      transgenic mice model. Immunized transgenic mice showed an increase in hIAPP
      antibody serum titer as well as improvement in diabetes-associated parameters.
      Lower fasting blood glucose levels, higher insulin, and lower islet amyloid
      polypeptide accumulation were observed. Furthermore, antibodies derived from the
      immunized mice reduced hIAPP oligomers cytotoxicity towards beta-cells in a dose
      dependent manner. This study highlights the significance of targeting the early
      amyloid self-assembly events for potential disease management. Furthermore, it
      demonstrates that alpha-helical oligomers conformers are valid epitope for the
      development of future immunization therapy.

PMID- 29070798
TI  - Remodeling of the Streptococcus mutans proteome in response to LrgAB and external
      stresses.
AB  - The Streptococcus mutans Cid/Lrg system represents an ideal model to study how
      this organism withstands various stressors encountered in the oral cavity.
      Mutation of lrgAB renders S. mutans more sensitive to oxidative, heat, and
      vancomycin stresses. Here, we have performed a comprehensive proteomics
      experiment using label-free quantitative mass spectrometry to compare the
      proteome changes of wild type UA159 and lrgAB mutant strains in response to these
      same stresses. Importantly, many of identified proteins showed either a
      strikingly large fold-change, or were completely suppressed or newly induced in
      response to a particular stress condition. Notable stress proteome changes
      occurred in a variety of functional categories, including amino acid
      biosynthesis, energy metabolism, protein synthesis, transport/binding, and
      transcriptional/response regulators. In the non-stressed growth condition,
      mutation of lrgAB significantly altered the abundance of 76 proteins (a fold
      change >1.4, or <0.6, p-value <0.05) and several of these matched the stress
      proteome of the wild type strain. Interestingly, the statistical correlation
      between the proteome changes and corresponding RNA-seq transcriptomic studies was
      relatively low (rho(rho) <0.16), suggesting that adaptation to a new environment
      may require radical proteome turnover or metabolic remodeling. Collectively, this
      study reinforces the importance of LrgAB to the S. mutans stress response.

PMID- 29070800
TI  - Observed drought indices show increasing divergence across Europe.
AB  - Recent severe European droughts raise the vital question: are we already
      experiencing measurable changes in drought likelihood that agree with climate
      change projections? The plethora of drought definitions compounds this question,
      requiring instead that we ask: how have various types of drought changed, how do
      these changes compare with climate projections, and what are the causes of
      observed differences? To our knowledge, this study is the first to reveal a
      regional divergence in drought likelihood as measured by the two most prominent
      meteorological drought indices: the Standardized Precipitation Index (SPI) and
      the Standardized Precipitation-Evapotranspiration Index (SPEI) across Europe over
      the period 1958-2014. This divergence is driven primarily by an increase in
      temperature from 1970-2014, which in turn increased reference evapotranspiration
      (ET0) and thereby drought area measured by the SPEI. For both indices, Europe
      wide analysis shows increasing drought frequencies in southern Europe and
      decreasing frequencies in northern Europe. Notably, increases in temperature and
      ET0 have enhanced droughts in southern Europe while counteracting increased
      precipitation in northern Europe. This is consistent with projections under
      climate change, indicating that climate change impacts on European drought may
      already be observable and highlighting the potential for discrepancies among
      standardized drought indices in a non-stationary climate.

PMID- 29070799
TI  - Controlled Self-assembly of Stem Cell Aggregates Instructs Pluripotency and
      Lineage Bias.
AB  - Stem cell-derived organoids and other 3D microtissues offer enormous potential as
      models for drug screening, disease modeling, and regenerative medicine. Formation
      of stem/progenitor cell aggregates is common in biomanufacturing processes and
      critical to many organoid approaches. However, reproducibility of current
      protocols is limited by reliance on poorly controlled processes (e.g.,
      spontaneous aggregation). Little is known about the effects of aggregation
      parameters on cell behavior, which may have implications for the production of
      cell aggregates and organoids. Here we introduce a bioengineered platform of
      labile substrate arrays that enable simple, scalable generation of cell
      aggregates via a controllable 2D-to-3D "self-assembly". As a proof-of-concept, we
      show that labile substrates generate size- and shape-controlled embryoid bodies
      (EBs) and can be easily modified to control EB self-assembly kinetics. We show
      that aggregation method instructs EB lineage bias, with faster aggregation
      promoting pluripotency loss and ectoderm, and slower aggregation favoring
      mesoderm and endoderm. We also find that aggregation kinetics of EBs markedly
      influence EB structure, with slower kinetics resulting in increased EB porosity
      and growth factor signaling. Our findings suggest that controlling internal
      structure of cell aggregates by modifying aggregation kinetics is a potential
      strategy for improving 3D microtissue models for research and translational
      applications.

PMID- 29070801
TI  - Gelatinizing oil in water and its removal via bacteria inhabiting the gels.
AB  - When crude oil samples were shaken (200 rpm) in seawater samples from the Arabian
      Gulf at 30  degrees C, usually oil-gels were produced spontaneously leaving the
      water quite clear. The gelators could probably be based on cholesteryl
      derivatives. Microscopic examination of the established gels revealed
      nanofibrellar structures similar to those described by earlier workers for
      artificially synthesized gelators. Communities of bacteria including prosthetic
      and stalked members as well as oil-degrading bacteria were recorded in such gels.
      Chemical analysis revealed that 88.5% of the oil entrapped by gelation was
      biodegraded after 40 days at 30  degrees C. Individual bacterial species isolated
      from the oil-gels biodegraded in batch cultures between 17.8 and 33.3% of the oil
      added at time zero in 12 days at 30  degrees C. Gelation is a promising approach,
      not only for clean, physical removal of oil spilled in aquatic habitats, as so
      far suggested, but also in its effective microbiological biodegradation, as the
      current study revealed.

PMID- 29070790
TI  - Pattern Discovery in Brain Imaging Genetics via SCCA Modeling with a Generic Non
      convex Penalty.
AB  - Brain imaging genetics intends to uncover associations between genetic markers
      and neuroimaging quantitative traits. Sparse canonical correlation analysis
      (SCCA) can discover bi-multivariate associations and select relevant features,
      and is becoming popular in imaging genetic studies. The L1-norm function is not
      only convex, but also singular at the origin, which is a necessary condition for
      sparsity. Thus most SCCA methods impose [Formula: see text]-norm onto the
      individual feature or the structure level of features to pursuit corresponding
      sparsity. However, the [Formula: see text]-norm penalty over-penalizes large
      coefficients and may incurs estimation bias. A number of non-convex penalties are
      proposed to reduce the estimation bias in regression tasks. But using them in
      SCCA remains largely unexplored. In this paper, we design a unified non-convex
      SCCA model, based on seven non-convex functions, for unbiased estimation and
      stable feature selection simultaneously. We also propose an efficient
      optimization algorithm. The proposed method obtains both higher correlation
      coefficients and better canonical loading patterns. Specifically, these SCCA
      methods with non-convex penalties discover a strong association between the APOE
      e4 rs429358 SNP and the hippocampus region of the brain. They both are
      Alzheimer's disease related biomarkers, indicating the potential and power of the
      non-convex methods in brain imaging genetics.

PMID- 29070802
TI  - Split GFP technologies to structurally characterize and quantify functional
      biomolecular interactions of FTD-related proteins.
AB  - Protein multimerization in physiological and pathological conditions constitutes
      an intrinsic trait of proteins related to neurodegeneration. Recent evidence
      shows that TDP-43, a RNA-binding protein associated with frontotemporal dementia
      and amyotrophic lateral sclerosis, exists in a physiological and functional
      nuclear oligomeric form, whose destabilization may represent a prerequisite for
      misfolding, toxicity and subsequent pathological deposition. Here we show the
      parallel implementation of two split GFP technologies, the GFP bimolecular and
      trimolecular fluorescence complementation (biFC and triFC) in the context of TDP
      43 self-assembly. These techniques coupled to a variety of assays based on
      orthogonal readouts allowed us to define the structural determinants of TDP-43
      oligomerization in a qualitative and quantitative manner. We highlight the
      versatility of the GFP biFC and triFC technologies for studying the localization
      and mechanisms of protein multimerization in the context of neurodegeneration.

PMID- 29070805
TI  - Strain induced polarization chaos in a solitary VCSEL.
AB  - Physical curiosity at the beginning, optical chaos is now attracting increasing
      interest in various technological areas such as detection and ranging or secure
      communications, to name but a few. However, the complexity of optical chaos
      generators still significantly hinders their development. In this context, the
      generation of chaotic polarization fluctuations in a single laser diode has
      proven to be a significant step forward, despite being observed solely for
      quantum-dot vertical-cavity surface-emitting lasers (VCSELs). Here, we
      demonstrate experimentally that a similar polarization dynamics can be
      consistently obtained in quantum-well VCSELs. Indeed, by introducing anisotropic
      strain in the laser cavity, we successfully triggered the desired chaotic
      dynamics. The simplicity of the proposed approach, based on low-cost and easily
      available components including off-the-shelf VCSELs, paves the way to the wide
      spread use of solitary VCSELs for chaos-based applications.

PMID- 29070803
TI  - MiR-193b regulates breast cancer cell migration and vasculogenic mimicry by
      targeting dimethylarginine dimethylaminohydrolase 1.
AB  - Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is responsible for metabolism
      of an endogenous inhibitor of nitric oxide synthase (NOS), asymmetric
      dimethylarginine (ADMA), which plays a key role in modulating angiogenesis. In
      addition to angiogenesis, tumours can establish a vascular network by forming
      vessel-like structures from tumour cells; a process termed vasculogenic mimicry
      (VM). Here, we identified over-expression of DDAH1 in aggressive MDA-MB-231, MDA
      MB-453 and BT549 breast cancer cell lines when compared to normal mammary
      epithelial cells. DDAH1 expression was inversely correlated with the microRNA miR
      193b. In DDAH1+ MDA-MB-231 cells, ectopic expression of miR-193b reduced DDAH1
      expression and the conversion of ADMA to citrulline. In DDAH1- MCF7 cells,
      inhibition of miR-193b elevated DDAH1 expression. Luciferase reporter assays
      demonstrated DDAH1 as a direct target of miR-193b. MDA-MB-231 cells organised
      into tube structures in an in vitro assay of VM, which was significantly
      inhibited by DDAH1 knockdown or miR-193b expression. Mechanistically, we found
      miR-193b regulates cell proliferation and migration of MDA-MB-231 cells, whilst
      DDAH1 knockdown inhibited cell migration. These studies represent the first
      evidence for DDAH1 expression, regulation and function in breast cancer cells,
      and highlights that targeting DDAH1 expression and/or enzymatic activity may be a
      valid option in the treatment of aggressive breast cancers.

PMID- 29070804
TI  - Digital reconstruction of the Ceprano calvarium (Italy), and implications for its
      interpretation.
AB  - The Ceprano calvarium was discovered in fragments on March 1994 near the town of
      Ceprano in southern Latium (Italy), embedded in Middle Pleistocene layers. After
      reconstruction, its morphological features suggests that the specimen belongs to
      an archaic variant of H. heidelbergensis, representing a proxy for the last
      common ancestor of the diverging clades that respectively led to H.
      neanderthalensis and H. sapiens. Unfortunately, the calvarium was taphonomically
      damaged. The postero-lateral vault, in particular, appears deformed and this
      postmortem damage may have influenced previous interpretations. Specifically,
      there is a depression on the fragmented left parietal, while the right cranial
      wall is warped and angulated. This deformation affected the shape of the
      occipital squama, producing an inclination of the transverse occipital torus. In
      this paper, after X-ray microtomography (MUCT) of both the calvarium and several
      additional fragments, we analyze consistency and pattern of the taphonomic
      deformation that affected the specimen, before the computer-assisted
      retrodeformation has been performed; this has also provided the opportunity to
      reappraise early attempts at restoration. As a result, we offer a revised
      interpretation for the Ceprano calvarium's original shape, now free from the
      previous uncertainties, along with insight for its complex depositional and
      taphonomic history.

PMID- 29070807
TI  - Functional characterization of the PHT1 family transporters of foxtail millet
      with development of a novel Agrobacterium-mediated transformation procedure.
AB  - Phosphate is an essential nutrient for plant growth and is acquired from the
      environment and distributed within the plant in part through the action of
      phosphate transporters of the PHT1 family. Foxtail millet (Setaria italica) is an
      orphan crop essential to the food security of many small farmers in Asia and
      Africa and is a model system for other millets. A novel Agrobacterium-mediated
      transformation and direct plant regeneration procedure was developed from shoot
      apex explants and used to downregulate expression of 3 members of the PHT1
      phosphate transporter family SiPHT1;2 SiPHT1;3 and SiPHT1;4. Transformants were
      recovered with close to 10% efficiency. The downregulation of individual
      transporters was confirmed by RT-PCR. Downregulation of individual transporters
      significantly reduced the total and inorganic P contents in shoot and root
      tissues and increased the number of lateral roots and root hairs showing they
      have non-redundant roles. Downregulation of SiPHT1;2 had the strongest effect on
      total and inorganic P in shoot and root tissues. Complementation experiments in
      S. cerevisiae provide evidence for the ability of SiPHT1;1, 1;2, 1;3, 1;7 and 1;8
      to function as high affinity Pi transporters. This work will aid development of
      improved millet varieties for global food security.

PMID- 29070808
TI  - Species composition and seasonal dynamics of aphid parasitoids and
      hyperparasitoids in wheat fields in northern China.
AB  - Parasitoids are important natural enemies of aphids in wheat fields of northern
      China, and interest in them has increased in recent years. However, little is
      known regarding parasitoids of wheat aphids, which has hindered the study and
      understanding of aphid-parasitoid interactions. In the present study, three
      primary parasitoids and 15 hyperparasitoids were collected in wheat fields during
      a 2-year survey in northern China (2014, 2015) and a 2-year investigation at
      Langfang, Hebei Province (2015, 2016). Among them, Aphidius uzbekistanicus
      Luzhetski was found most frequently among the primary parasitoids, while
      Pachyneuron aphidis (Bouche) dominated the hyperparasitoid community.
      Investigation of the dynamics of wheat aphids and parasitoids revealed that the
      primary parasitoids appeared early in the growing period and that the
      hyperparasitoids appeared later. Analysis of the seasonal dynamics revealed that
      growth of the parasitoid population followed that of the aphid population and
      that the parasitism rates were highest in the late growing period.

PMID- 29070806
TI  - Expression and regulation of long noncoding RNAs during the osteogenic
      differentiation of periodontal ligament stem cells in the inflammatory
      microenvironment.
AB  - Although long noncoding RNAs (lncRNAs) have been emerging as critical regulators
      in various tissues and biological processes, little is known about their
      expression and regulation during the osteogenic differentiation of periodontal
      ligament stem cells (PDLSCs) in inflammatory microenvironment. In this study, we
      have identified 63 lncRNAs that are not annotated in previous database. These
      novel lncRNAs were not randomly located in the genome but preferentially located
      near protein-coding genes related to particular functions and diseases, such as
      stem cell maintenance and differentiation, development disorders and inflammatory
      diseases. Moreover, we have identified 650 differentially expressed lncRNAs among
      different subsets of PDLSCs. Pathway enrichment analysis for neighboring protein
      coding genes of these differentially expressed lncRNAs revealed stem cell
      differentiation related functions. Many of these differentially expressed lncRNAs
      function as competing endogenous RNAs that regulate protein-coding transcripts
      through competing shared miRNAs.

PMID- 29070811
TI  - Inflammation: Specific inhibition of NLRP3 comes closer.

PMID- 29070809
TI  - Efficient protein production by yeast requires global tuning of metabolism.
AB  - The biotech industry relies on cell factories for production of pharmaceutical
      proteins, of which several are among the top-selling medicines. There is,
      therefore, considerable interest in improving the efficiency of protein
      production by cell factories. Protein secretion involves numerous intracellular
      processes with many underlying mechanisms still remaining unclear. Here, we use
      RNA-seq to study the genome-wide transcriptional response to protein secretion in
      mutant yeast strains. We find that many cellular processes have to be attuned to
      support efficient protein secretion. In particular, altered energy metabolism
      resulting in reduced respiration and increased fermentation, as well as balancing
      of amino-acid biosynthesis and reduced thiamine biosynthesis seem to be
      particularly important. We confirm our findings by inverse engineering and
      physiological characterization and show that by tuning metabolism cells are able
      to efficiently secrete recombinant proteins. Our findings provide increased
      understanding of which cellular regulations and pathways are associated with
      efficient protein secretion.

PMID- 29070810
TI  - Complement receptors C5aR1 and C5aR2 act differentially during the early immune
      response after bone fracture but are similarly involved in bone repair.
AB  - Severely injured patients frequently suffer compromised fracture healing because
      of systemic post-traumatic inflammation. An important trigger of the
      posttraumatic immune response is the complement anaphylatoxin C5a, which acts via
      two receptors, C5aR1 and C5aR2, expressed on immune and bone cells. The blockade
      of C5a-mediated inflammation during the early inflammatory phase was demonstrated
      to improve fracture healing after severe injury. However, the distinct roles of
      the two complement receptors C5aR1 and C5aR2 in bone has to date not been
      studied. Here, we investigated bone turnover and regeneration in mice lacking
      either C5aR1 or C5aR2 in a model of isolated fracture and after severe injury,
      combining the fracture with an additional thoracic trauma. Both C5aR1-/- and
      C5aR2-/- mice displayed an increased bone mass compared to wild-type controls due
      to reduced osteoclast formation and increased osteoblast numbers, respectively.
      Following fracture, the inflammatory response was differently affected in these
      strains: It was decreased in C5aR1-/- mice but enhanced in C5aR2-/- mice. Both
      strains exhibited impaired fracture healing, disturbed osteoclastogenesis and
      delayed cartilage-to-bone transformation. Thus, our data suggest that C5aR1 and
      C5aR2 differentially regulate the immune response after fracture and are required
      for effective cartilage-to-bone transformation in the fracture callus and for
      undisturbed bone healing.

PMID- 29070813
TI  - The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in
      pattern separation and object recognition memory.
AB  - Both recognition of familiar objects and pattern separation, a process that
      orthogonalises overlapping events, are critical for effective memory. Evidence is
      emerging that human pattern separation requires dentate gyrus. Dentate gyrus is
      intimately connected to CA3 where, in animals, an autoassociative network enables
      recall of complete memories to underpin object/event recognition. Despite huge
      motivation to treat age-related human memory disorders, interaction between human
      CA3 and dentate subfields is difficult to investigate due to small size and
      proximity. We tested the hypothesis that human dentate gyrus is critical for
      pattern separation, whereas, CA3 underpins identical object recognition. Using 3
      T MR hippocampal subfield volumetry combined with a behavioural pattern
      separation task, we demonstrate that dentate gyrus volume predicts accuracy and
      response time during behavioural pattern separation whereas CA3 predicts
      performance in object recognition memory. Critically, human dentate gyrus volume
      decreases with age whereas CA3 volume is age-independent. Further, decreased
      dentate gyrus volume, and no other subfield volume, mediates adverse effects of
      aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in
      human memory and uncover the variegated effects of human ageing across
      hippocampal regions. Accurate pinpointing of focal memory-related deficits will
      allow future targeted treatment for memory loss.

PMID- 29070815
TI  - Unveiling the physical mechanism behind pistol shrimp cavitation.
AB  - Snapping shrimps use a special shaped claw to generate a cavitating high speed
      water jet. Cavitation formed in this way, may be used for hunting/stunning prey
      and communication. The present work is a novel computational effort to provide
      insight on the mechanisms of cavitation formation during the claw closure. The
      geometry of the claw used here is a simplified claw model, based on prior
      experimental work. Techniques, such as Immersed Boundary and Homogenous
      Equilibrium Model (HEM), are employed to describe the claw motion and cavitating
      flow field respectively. The simulation methodology has been validated against
      prior experimental work and is applied here for claw closure at realistic
      conditions. Simulations show that during claw closure, a high velocity jet forms,
      inducing vortex roll-up around it. If the closure speed is high enough, the
      intensity of the swirling motion is enough to produce strong depressurization in
      the vortex core, leading to the formation of a cavitation ring. The cavitation
      ring moves along the jet axis and, soon after its formation, collapses and
      rebounds, producing high pressure pulses.

PMID- 29070814
TI  - Persistent elevation of postoperative neutrophil-to-lymphocyte ratio: A better
      predictor of survival in gastric cancer than elevated preoperative neutrophil-to
      lymphocyte ratio.
AB  - Postoperative neutrophil-to-lymphocyte ratio change (NLRc) reflects the dynamic
      change of balance between host inflammatory response and immune response after
      treatment. In gastric cancer, an elevated initial NLR (iNLR) is reported to be a
      prognostic predictor, but the clinical application of the NLRc remains unclear.
      The NLRc was assessed in 734 patients undergoing total/subtotal gastrectomy and
      endoscopic submucosal dissection for gastric adenocarcinoma. The iNLR and NLRc
      were recorded within 10 days of the first diagnosis and 3-6 months after surgery,
      respectively. Using receiver operating characteristic (ROC) curves, we
      investigated the relationship between NLRc or iNLR and patient survival. The
      analysis revealed a higher predictive power for correlating patient survival with
      the NLRc compared with iNLR. NLRc was defined as negative (lower than iNLR) and
      positive (higher than iNLR). A positive NLRc was frequently observed in patients
      with advanced AJCC stage, local recurrence, distant metastasis, perineural
      invasion, and adjuvant chemotherapy (all p < 0.05). Univariate and multivariate
      analyses revealed a significant relationship between patient survival and NLRc
      (all p < 0.05) but no association between survival and iNLR. The NLRc could be a
      better indicator than iNLR for predicting survival in patients with gastric
      cancer.

PMID- 29070812
TI  - Evidence-based scientific exercise guidelines for adults with spinal cord injury:
      an update and a new guideline.
AB  - OBJECTIVES: To describe the process and outcomes of using a new evidence base to
      develop scientific guidelines that specify the type and minimum dose of exercise
      necessary to improve fitness and cardiometabolic health in adults with spinal
      cord injury (SCI). SETTING: International. METHODS: Using Appraisal of
      Guidelines, Research and Evaluation (AGREE) II reporting criteria, steps included
      (a) determining the guidelines' scope; (b) conducting a systematic review of
      relevant literature; (c) holding three consensus panel meetings (European,
      Canadian and International) to formulate the guidelines; (d) obtaining
      stakeholder feedback; and (e) process evaluation by an AGREE II consultant.
      Stakeholders were actively involved in steps (c) and (d). RESULTS: For
      cardiorespiratory fitness and muscle strength benefits, adults with a SCI should
      engage in at least 20 min of moderate to vigorous intensity aerobic exercise 2
      times per week AND 3 sets of strength exercises for each major functioning muscle
      group, at a moderate to vigorous intensity, 2 times per week (strong
      recommendation). For cardiometabolic health benefits, adults with a SCI are
      suggested to engage in at least 30 min of moderate to vigorous intensity aerobic
      exercise 3 times per week (conditional recommendation). CONCLUSIONS: Through a
      systematic, rigorous, and participatory process involving international
      scientists and stakeholders, a new exercise guideline was formulated for
      cardiometabolic health benefits. A previously published SCI guideline was
      endorsed for achieving fitness benefits. These guidelines represent an important
      step toward international harmonization of exercise guidelines for adults with
      SCI, and a foundation for developing exercise policies and programs for people
      with SCI around the world.

PMID- 29070816
TI  - Resistance to checkpoint blockade therapy through inactivation of antigen
      presentation.
AB  - Treatment with immune checkpoint blockade (CPB) therapies often leads to
      prolonged responses in patients with metastatic melanoma, but the common
      mechanisms of primary and acquired resistance to these agents remain incompletely
      characterized and have yet to be validated in large cohorts. By analyzing
      longitudinal tumor biopsies from 17 metastatic melanoma patients treated with CPB
      therapies, we observed point mutations, deletions or loss of heterozygosity (LOH)
      in beta-2-microglobulin (B2M), an essential component of MHC class I antigen
      presentation, in 29.4% of patients with progressing disease. In two independent
      cohorts of melanoma patients treated with anti-CTLA4 and anti-PD1, respectively,
      we find that B2M LOH is enriched threefold in non-responders (~30%) compared to
      responders (~10%) and associated with poorer overall survival. Loss of both
      copies of B2M is found only in non-responders. B2M loss is likely a common
      mechanism of resistance to therapies targeting CTLA4 or PD1.

PMID- 29070817
TI  - Structure based biophysical characterization of the PROPPIN Atg18 shows Atg18
      oligomerization upon membrane binding.
AB  - PROPPINs (beta-propellers that bind polyphosphoinositides) are PtdIns3P and
      PtdIns(3,5)P2 binding autophagy related proteins. They contain two
      phosphatidylinositolphosphate (PIP) binding sites and a conserved FRRG motif is
      essential for PIP binding. Here we present the 2.0 A resolution crystal structure
      of the PROPPIN Atg18 from Pichia angusta. We designed cysteine mutants for
      labelling with the fluorescence dyes to probe the distances of the mutants to the
      membrane. These measurements support a model for PROPPIN-membrane binding, where
      the PROPPIN sits in a perpendicular or slightly tilted orientation on the
      membrane. Stopped-flow measurements suggest that initial PROPPIN-membrane binding
      is driven by non-specific PIP interactions. The FRRG motif then retains the
      protein in the membrane by binding two PIP molecules as evident by a lower
      dissociation rate for Atg18 in comparison with its PIP binding deficient FTTG
      mutant. We demonstrate that the amine-specific cross-linker
      Bis(sulfosuccinimidyl)suberate (BS3), which is used for protein-protein cross
      linking can also be applied for cross-linking proteins and
      phosphatidylethanolamine (PE). Cross-linking experiments with liposome bound
      Atg18 yielded several PE cross-linked peptides. We also observed intermolecular
      cross-linked peptides, which indicated Atg18 oligomerization. FRET-based stopped
      flow measurements revealed that Atg18 rapidly oligomerizes upon membrane binding
      while it is mainly monomeric in solution.

PMID- 29070818
TI  - Direct Evidence of Adult Aedes albopictus Dispersal by Car.
AB  - Whereas the Asian tiger mosquito (Aedes albopictus) has low active dispersal
      capabilities, its worldwide colonization has been rapid. Indirect evidence and
      informal reports have long implicated passive transportation in cars, but this
      has not previously been studied systematically given the difficulties of real
      time roadside surveys. Here we report the first sampling study confirming that
      adult tiger mosquitoes travel with humans in cars and enabling us to estimate the
      frequency of these events. We combine the results with citizen science data to
      model the car-facilitated dispersal of Aedes albopictus at a nationwide level.
      During the summer of 2015, we sampled 770 cars in north-eastern Spain,
      discovering 4 adult female tiger mosquitoes that had entered cars prior to
      sampling. Our Bayesian model suggests that of the 6.5 million daily car trips in
      the Barcelona metropolitan area, between 13,000 and 71,500 facilitate tiger
      mosquito movement, and that Barcelona is the largest source of inter-province
      tiger mosquito transfers in Spain. Our results are supported by expert-validated
      citizen science data, and will contribute to better understanding the tiger
      mosquito's invasion process and ultimately lead to more effective vector control
      strategies.

PMID- 29070820
TI  - Tropical protected areas reduced deforestation carbon emissions by one third from
      2000-2012.
AB  - Tropical deforestation is responsible for around one tenth of total anthropogenic
      carbon emissions, and tropical protected areas (PAs) that reduce deforestation
      can therefore play an important role in mitigating climate change and protecting
      biodiversity and ecosystem services. While the effectiveness of PAs in reducing
      deforestation has been estimated, the impact on global carbon emissions remains
      unquantified. Here we show that tropical PAs overall reduced deforestation carbon
      emissions by 4.88 Pg, or around 29%, between 2000 and 2012, when compared to
      expected rates of deforestation controlling for spatial variation in
      deforestation pressure. The largest contribution was from the tropical Americas
      (368.8 GgC y-1), followed by Asia (25.0 GgC y-1) and Africa (12.7 GgC y-1).
      Variation in PA effectiveness is largely driven by local factors affecting
      individual PAs, rather than designations assigned by governments.

PMID- 29070822
TI  - Reduction in cholera deaths targeted for 2030.

PMID- 29070823
TI  - Finding life's missing pieces.

PMID- 29070821
TI  - Evaluation of the Effectiveness of Xanthine Oxidoreductase Inhibitors on
      Haemodialysis Patients using a Marginal Structural Model.
AB  - A lower serum uric acid (UA) level has been associated with a higher mortality
      rate in haemodialysis patients. We investigated the long-term confounding factors
      of UA and mortality, and fitted a marginal structural model (MSM) based on the
      causal effect of xanthine oxidoreductase inhibitors (XORi). In total, 2429
      patients on regular dialysis from April 2013 to March 2016 were included, and
      divided into quintiles by serum UA with Kaplan Meier (KM) curves and log rank
      analysis. Baseline characteristics were evaluated for relationships with all
      cause mortality and cardiovascular disease (CVD) using the Cox hazard model. The
      MSM was used to control for time-dependent confounders of the XORi treatment
      effect. KM curves indicated that patients in the highest UA quintile had better
      outcomes than those in the lowest UA quintile. UA was not correlated with all
      cause mortality or CVD events in the Cox model; however, the hazard ratio (HR)
      for mortality was 0.96 for the baseline administration of XORi. The MSM analysis
      for the effect of XORi treatment on all-cause mortality revealed a HR of 0.24
      (95% confidence interval: 0.15-0.38) in all cohorts. These results suggest that
      XORi improved all-cause mortality in end-stage renal disease, irrespective of the
      serum UA level.

PMID- 29070824
TI  - Zika virus targets blood monocytes.

PMID- 29070819
TI  - Minocycline modulates microglia polarization in ischemia-reperfusion model of
      retinal degeneration and induces neuroprotection.
AB  - Retinal ischemia-reperfusion (IR) injury causes irreversible loss of neurons and
      ultimately leads to permanent visual impairment and blindness. The cellular
      response under this pathological retinal condition is less clear. Using
      genetically modified mice, we systematically examined the behavior of
      microglia/macrophages after injury. We show that IR leads to activation of
      microglia/macrophages indicated by migration and proliferation of resident
      microglia and recruitment of circulating monocytes. IR-induced
      microglia/macrophages associate with apoptotic retinal neurons. Very
      interestingly, neuron loss can be mitigated by minocycline treatment. Minocycline
      induces Il4 expression and M2 polarization of microglia/macrophages. IL4
      neutralization dampens minocycline-induced M2 polarization and neuroprotection.
      Given a well-established safety profile as an antibiotic, our results provide a
      rationale for using minocycline as a therapeutic agent for treating ischemic
      retinal degeneration.

PMID- 29070825
TI  - Melanopsin, a Canonical Light Receptor, Mediates Thermal Activation of Clock
      Genes.
AB  - Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically
      photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play
      a role in synchronizing the central circadian pacemaker to the astronomical day
      by conveying information about ambient light to the hypothalamic suprachiasmatic
      nucleus, the site of the master clock. We evaluated the effect of a heat stimulus
      (39.5  degrees C) on clock gene (Per1 and Bmal1) expression in cultured murine
      Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma
      cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4
      knockdown by small interfering RNA (siRNA). In addition, we evaluated the effects
      of heat shock on the localization of melanopsin by immunocytochemistry. In both
      cell lines melanopsin was found in a region capping the nucleus and heat shock
      did not affect its location. The heat-induced increase of Per1 expression was
      inhibited when melanopsin was pharmacologically blocked by AA92593 as well as
      when its protein expression was suppressed by siRNA in both Melan-a and B16-F10
      cells. These data strongly suggest that melanopsin is required for thermo
      reception, acting as a thermo-opsin that ultimately feeds the local circadian
      clock in mouse melanocytes and melanoma cells.

PMID- 29070827
TI  - Information Connections among Multiple Investors: Evolutionary Local Patterns
      Revealed by Motifs.
AB  - The concept of motifs provides a fresh perspective for studying local patterns,
      which is useful for understanding the essence of a network structure. However,
      few previous studies have focused on the evolutionary characteristics of weighted
      motifs while further considering participants' differences. We study how
      information connections differ among multiple investors. The evolutionary 10-year
      trend of weighted 3-motifs in China's energy stock markets is explored for the
      networks of co-holding behaviors among shareholders, who are classified as
      companies, funds and individuals. Our works allow us to detect the preferential
      local patterns distributed among different agents as their fluctuate involvement
      in networks. We find that the diversity of shareholders contributes to the
      statistical significance of local patterns, while homophily always exist among
      individuals. Modules of information connections are stable among reserved
      investors, which is especially apparent among companies. Individuals prefer to
      keep their connections with companies and funds. Unsteady modules happen owing to
      strengthen links among funds during the time that they are main participants in
      stock markets. More details about multiple investors informationally connected in
      evolutionary local patterns can be detected by our work.

PMID- 29070828
TI  - High blood pressure and its relationship to adiposity in a school-aged
      population: body mass index vs waist circumference.
AB  - High blood pressure (HBP) is a major concern in pediatric populations. Adiposity
      is highly related to HBP in youths; however, whether body mass index (BMI) or
      waist circumference (WC) is more strongly associated with HBP in this population
      is unclear. This cross-sectional study, involving schoolchildren between 10 and
      17 years of age from public and private schools, assessed direct measurements of
      BMI, WC and blood pressure. The socioeconomic level, sedentary behavior, physical
      activity, alcohol consumption and smoking history were obtained through a
      questionnaire. A Pearson's correlation and linear regression were used. In total,
      1011 adolescents with a mean age of 13.1 (+2.3) years were evaluated. The
      prevalence of overweight/obesity was 27.7%, and the percentage of abdominal
      obesity was 19.3%. Adolescent boys and girls who had overweight/obesity or
      abdominal obesity had higher systolic and diastolic blood pressure (BP) values
      compared with eutrophic adolescents or those without abdominal obesity. In
      general, both BMI and WC were related to BP, but WC was more strongly correlated
      with BP than BMI. In conclusion, although both BMI and WC were related to HBP, WC
      was more strongly associated with blood pressure in young people.

PMID- 29070830
TI  - Environmental stress and vestibular inputs modulate cardiovascular responses to
      orthostasis in hypertensive rats.
AB  - The frequent accompaniment of hypertension by orthostatic circulatory disorders
      prompted us to investigate the effect of repeated and sustained head-up and head
      down tilt positions on cardiovascular responses in spontaneously hypertensive
      rats vs. Wistar rats using radiotelemetric implants. Repeated orthostasis caused
      a transient elevation in blood pressure (7.3+/-1.7 mmHg) and heart rate (39.7+/
      10.5 BPM), while repeated antiorthostasis led only to reversible tachycardia
      (85.6+/-11.7-54.3+/-16.8 BPM) in spontaneously hypertensive rats. In contrast to
      the Wistar rats, sustained tilt failed to affect the blood pressure or heart rate
      in spontaneously hypertensive rats because the environmental stress of being
      placed in horizontal tilt cages prior to the sustained tilt test induced marked
      changes in cardiovascular parameters. Non-specific stress responses were
      eliminated both by the anxiolytic diazepam and a sub-anesthetic dose of
      chloralose. Unlike diazepam, chloralose amplified the orthostatic pressor
      responses in the Wistar rats. In contrast to diazepam preventing the pressor
      response and associated tachycardia in spontaneously hypertensive rats,
      chloralose elicited this effect during both sustained orthostasis (36.0+/-7.3
      mmHg, 63.7+/-21.8 BPM) and antiorthostasis (42.9+/-10.9 mmHg, 82.8+/-25.4 BPM),
      with a reduced baroreflex sensitivity. However, during sustained orthostasis,
      removal of the vestibular input led to a depressor response with bradycardia
      (12.5+/-3.2 mmHg, 59.3+/-17.3 BPM), whereas antiorthostasis only reduced blood
      pressure (20.5+/-7.1 mmHg) in the spontaneously hypertensive rats. We conclude
      that repeated tilts induce a transient pressor response and/or tachycardia in
      spontaneously hypertensive rats. Cardiovascular parameters are suppressed by
      diazepam, whereas chloralose evokes both blood pressure and heart rate responses
      during sustained tilts, which are primarily elicited by baroreflex suppression in
      hypertension. Vestibular inputs support cardiovascular tolerance to sustained
      postural changes in a rat model of human 'essential' hypertension.

PMID- 29070831
TI  - Inhibition of lobuloalveolar development by FOXC1 overexpression in the mouse
      mammary gland.
AB  - The forkhead box transcription factor FOXC1 plays a critical role in
      embryogenesis and the development of many organs. Its mutations and high
      expression are associated with many human diseases including breast cancer.
      Although FOXC1 knockout mouse studies showed that it is not required for mammary
      gland development during puberty, it is not clear whether its overexpression
      alters normal mammary development in vivo. To address this question, we generated
      transgenic mice with mammary-specific FOXC1 overexpression. We report that
      transgenic FOXC1 overexpression suppresses lobuloalveologenesis and lactation in
      mice. This phenotype is associated with higher percentages of estrogen receptor-,
      progesterone receptor-, or ki67-positive mammary epithelial cells in the
      transgenic mice at the lactation stage. We also show that expression of the Elf5
      transcription factor, a master regulator of mammary alveologenesis and luminal
      cell differentiation, is markedly reduced in mammary epithelial cells of
      transgenic mice. Likewise, levels of activated Stat5, another inducer of alveolar
      expansion and a known mediator of the Elf5 effect, are also lowered in those
      cells. In contrast, the cytokeratin 8-positive mammary cell population with
      progenitor properties is elevated in the transgenic mice at the lactation stage,
      suggesting inhibition of mammary cell differentiation. These results may
      implicate FOXC1 as a new important regulator of mammary gland development.

PMID- 29070829
TI  - Hemoglobin A1c and C-reactive protein are independently associated with blunted
      nocturnal blood pressure dipping in obesity-related prediabetes.
AB  - Blunted nocturnal dipping in blood pressure (BP) is associated with increased
      cardiovascular disease (CVD) risk in middle-aged/older adults. The prevalence of
      blunted nocturnal BP dipping is higher in persons with obesity and diabetes,
      conditions that are also associated with elevated aortic stiffness and
      inflammation. Therefore, we hypothesized that elevated glycemia, inflammation and
      aortic stiffness would be inversely associated with the magnitude of nocturnal
      systolic BP dipping among middle-aged/older adults with obesity at high CVD risk.
      Twenty-four hour ambulatory BP monitoring, aortic stiffness (carotid-femoral
      pulse wave velocity, CF-PWV), hemoglobin A1c (HbA1c) and inflammation (C-reactive
      protein, CRP) were measured in 86 middle-aged/older adults with obesity and at
      least one other CVD risk factor (age 40-74 years; 34 male/52 female; body mass
      index=36.7+/-0.5 kg m-2; HbA1c=5.7+/-0.04%). In the entire cohort, CRP
      (beta=0.40+/-0.20, P=0.04), but not HbA1c or CF-PWV was independently associated
      with systolic BP dipping percent (Model R2=0.07, P=0.12). In stratified (that is,
      presence or absence of prediabetes) multiple linear regression analysis, HbA1c
      (beta=6.24+/-2.6, P=0.02) and CRP (beta=0.57+/-0.2, P=0.01), but not CF-PWV
      (beta=0.14+/- 2.6, P=0.74), were independently associated with systolic BP
      dipping percent (Model R2=0.32, P<0.01) in obese adults with prediabetes but were
      absent in obese adults without prediabetes (Model R2=0.01 P=0.95). However,
      nocturnal systolic BP dipping percent (P=0.65), CF-PWV (P=0.68) and CRP (P=0.59)
      were similar between participants with and without prediabetes. These data
      suggest that impaired long-term glycemic control and higher inflammation may
      contribute partly to blunted BP dipping in middle-aged/older adults with obesity
      related prediabetes.

PMID- 29070832
TI  - Prediction of Cross-resistance and Collateral Sensitivity by Gene Expression
      profiles and Genomic Mutations.
AB  - In adaptive evolution, an increase in fitness to an environment is frequently
      accompanied by changes in fitness to other environmental conditions, called cross
      resistance and sensitivity. Although the networks between fitness changes affect
      the course of evolution substantially, the mechanisms underlying such fitness
      changes are yet to be fully elucidated. Herein, we performed high-throughput
      laboratory evolution of Escherichia coli under various stress conditions using an
      automated culture system, and quantified how the acquisition of resistance to one
      stressor alters the resistance to other stressors. We demonstrated that
      resistance changes could be quantitatively predicted based on changes in the
      transcriptome of the resistant strains. We also identified several genes and gene
      functions, for which mutations were commonly fixed in the strains resistant to
      the same stress, which could partially explain the observed cross-resistance and
      collateral sensitivity. The integration of transcriptome and genome data enabled
      us to clarify the bacterial stress resistance mechanisms.

PMID- 29070826
TI  - Genetic insights into the neurodevelopmental origins of schizophrenia.
AB  - Schizophrenia is a severe neuropsychiatric disorder with a longstanding history
      of neurobiological investigation. Although the underlying causal mechanisms
      remain unknown, early neurodevelopmental events have been implicated in
      pathogenesis, initially by epidemiological and circumstantial data but more
      recently by brain-specific molecular and genetic findings. Notably, genomic
      research has recently uncovered discrete risk variants and risk loci associated
      with schizophrenia, with the potential to elucidate disease mechanisms. This
      Review revisits the neurodevelopmental model of schizophrenia from a current
      genetics perspective, delineating the complex genetic basis of the disorder and
      highlighting gene expression and epigenetic analyses of post-mortem cortical
      tissue that suggest that early brain development mediates genetic risk associated
      with schizophrenia. Future functional genomics investigations will accordingly
      need to characterize schizophrenia risk loci in relevant neurodevelopmental
      models.

PMID- 29070833
TI  - Ionic Circuits Powered by Reverse Electrodialysis for an Ultimate Iontronic
      System.
AB  - Despite numerous reports on iontronic devices, there has been no whole circuit
      working in aqueous media including even power source. Herein, we introduce
      complete ionic circuits powered by reverse electrodialysis (RED) for the first
      time without employing any electronic components. The RED-driven polyelectrolyte
      diode successfully shows rectification behavior which is verified by monitoring
      dynamic ion distribution through fluorescence in real-time. We can also turn on
      and off the voltage applied to the circuit, and apply an arbitrary voltage by
      precisely manipulating the pressure imposed to an elastic connection tube filled
      with electrolyte. Furthermore, this new concept containing ionic power source
      advances to a more sophisticated ionic OR logic gate. The proposed system paves
      the way to develop not only passive iontronic devices (e.g. current ionic diode),
      but active ones requiring a source of energy, particularly such as a neuron-like
      information processor powered by fully ionic systems, and thereby aqueous
      computers.

PMID- 29070834
TI  - Myocardial changes in incident haemodialysis patients over 6-months: an
      observational cardiac magnetic resonance imaging study.
AB  - Patients commencing on haemodialysis (HD) have an increased risk of
      cardiovascular events in the first year after starting HD compared to those
      patients established on HD longer. Left ventricular (LV) hypertrophy and abnormal
      myocardial strain predict mortality. There may be changes in the myocardium of
      incident HD patients over a 6-month period of HD which may explain changes in
      cardiovascular risk. We used CMR to consider changes in LV mass, myocardial
      strain and T1 mapping. We examined changes in pre-dialysis highly sensitive
      troponin T. 33 patients undergoing HD for <12 months were recruited. Participants
      underwent CMR at baseline and after 6-months of standard care. 6-months of HD was
      associated with reduction in LV mass index (Baseline: 78.8 g/m2 follow up: 69.9
      g/m2, p = <0.001). LV global longitudinal strain also improved (Baseline: -17.9%,
      follow up: -21.6%, p = <0.001). Change in T1 time was not significant (Baseline
      septal T1 1277.4 ms, follow up 1271.5 p = 0.504). Highly sensitive troponin T was
      lower at follow up (Baseline 38.8 pg/L, follow up 30.8 pg/L p = 0.02). In
      incident HD patients, 6-months of HD was associated with improvements in LV mass,
      strain and troponin. These findings may reflect improvement in known cardiac
      tissue abnormalities found in patients over the first year of HD.

PMID- 29070836
TI  - Dual negative roles of C/EBPalpha in the expansion and pro-tumor functions of
      MDSCs.
AB  - Myeloid-derived suppressor cells (MDSCs) are greatly expanded in cancer patients
      and tumor-bearing mice. They infiltrate into tumors and modulate the tumor
      microenvironment. In an effort to identify molecular mediators responsible for
      expansion and the tumor-promoting function of MDSCs, we discovered CCAAT/enhancer
      binding protein alpha (C/EBPalpha) expression was significantly reduced in MDSCs
      from tumor-bearing mice compared to non-tumor-bearing hosts. Tumor-conditioned
      medium down-regulated C/EBPalpha expression, suggesting tumor secreted factors
      inhibiting the gene expression. Consistent with the function of C/EBPalpha in
      regulating the balance between proliferation and growth arrest in hematopoietic
      progenitors, myeloid lineage specific deletion of C/EBPalpha resulted in
      significantly enhanced MDSC proliferation and expansion, as well as an increase
      of myeloid progenitors and a decrease of mature cells. In addition, deletion of
      C/EBPalpha in MDSCs enhanced the pro-angiogenic, immune suppressive and pro
      tumorigenic behavior of these cells by upregulating the production of iNOS and
      arginase, as well as MMP-9 and VEGF. Accordingly, tumors growing in C/EBPalpha
      conditional null mice displayed greater MDSC infiltration, increased
      vascularization and accelerated tumor growth. Taken together, this study reveals
      dual negative roles of C/EBPalpha in the expansion as well as pro-angiogenic and
      immune suppressive functions in MDSCs.

PMID- 29070835
TI  - Ultrathin two-dimensional porous organic nanosheets with molecular rotors for
      chemical sensing.
AB  - Molecular rotors have played an important role in recent materials chemistry.
      Although several studies on functional materials containing molecular rotors have
      been reported for fluorescence sensing, this concept has yet to be realized in
      two-dimensional (2D) materials. Here we report the preparation of all-carbon, pi
      conjugated 2D porous organic nanosheets, named NUS-24, which contain flexible
      tetraphenylethylene (TPE) units as the molecular rotors. NUS-24 nanosheets
      exhibit high stability, large lateral size, and ultrathin thickness (2-5 nm). The
      dynamic TPE rotors exposed on the surface of NUS-24 nanosheets can be restricted
      in the aggregated state with different water fractions, which is reminiscent of
      the aggregation-induced emission mechanism, thereby leading to the size-selective
      turn-on fluorescence by volatile organic compounds. Significantly, the ultrathin
      2D nanosheets and its composite membranes show much higher sensitivity and
      selectivity toward Fe3+ ions and nitro-containing compounds sensing, suggesting
      their potential applications in explosive detection and environmental monitoring.

PMID- 29070837
TI  - Factors controlling throughfall in a Pinus tabulaeformis forest in North China.
AB  - The factors that control throughfall in Pinus tabulaeformis plantations were
      investigated using linear and curve analyses based on direct measurements of
      rainfall, throughfall and stemflow from 36 rainfall events. The results showed
      the following: (1) there was significant spatial heterogeneity in throughfall
      rates in P. tabulaeformis plots; (2) the throughfall rate increased with
      increasing rainfall; and (3) the rate of increase gradually decreased. When
      rainfall reached approximately 25 mm, the throughfall rate stabilized. The
      coefficient of variation of the throughfall rate decreased with increasing
      rainfall, with a peak at approximately 10 mm of rainfall. The coefficient of
      variation of throughfall stabilized at 20%, and the coefficient of variation of
      the throughfall rate stabilized at 17%. A linear regression equation (R2 = 0.76)
      was derived by fitting the P. tabulaeformis average diameter at breast height
      (DBH), average tree height, average branch height, stand density, canopy
      thickness, canopy density, and the rainfall and throughfall rate. A highly
      positive correlation was found between the throughfall rate, canopy density,
      rainfall class and tree height (P < 0.01). By establishing a quadratic response
      surface model of the stand structure indicators and the throughfall rate, R2 was
      increased to 0.85 (P < 0.01). The quadratic regression analysis demonstrated a
      highly positive correlation between throughfall rate, canopy density and rainfall
      class.

PMID- 29070838
TI  - Inertia-driven resonant excitation of a magnetic skyrmion.
AB  - Topological spin structures such as magnetic domain walls, vortices, and
      skyrmions, have been receiving great interest because of their high potential
      application in various spintronic devices. To utilize them in the future
      spintronic devices, it is first necessary to understand the dynamics of the
      topological spin structures. Since inertial effect plays a crucial role in the
      dynamics of a particle, understanding the inertial effect of topological spin
      structures is an important task. Here, we report that a strong inertial effect
      appears steadily when a skyrmion is driven by an oscillating spin-Hall-spin
      torque (SHST). We find that the skyrmion exhibits an inertia-driven hypocycloid
      type trajectory when it is excited by the oscillating SHST. This motion has not
      been achieved by an oscillating magnetic field, which only excites the breathing
      mode without the inertial effect. The distinct inertial effect can be explained
      in terms of a spin wave excitation in the skyrmion boundary which is induced by
      the non-uniform SHST. Furthermore, the inertia-driven resonant excitation
      provides a way of experimentally estimating the inertial mass of the skyrmion.
      Our results therefore pave the way for the development of skyrmion-based device
      applications.

PMID- 29070839
TI  - Phosphorylable tyrosine residue 162 in the double-stranded RNA-dependent kinase
      PKR modulates its interaction with SUMO.
AB  - Activated dsRNA-dependent serine/threonine kinase PKR phosphorylates the alpha
      subunit of eukaryotic initiation factor 2 (eIF2alpha), resulting in a shut-off of
      general translation, induction of apoptosis, and inhibition of virus replication.
      PKR can be activated by binding to dsRNA or cellular proteins such as PACT/RAX,
      or by its conjugation to ISG15 or SUMO. Here, we demonstrate that PKR also
      interacts with SUMO in a non-covalent manner. We identify the phosphorylable
      tyrosine residue 162 in PKR (Y162) as a modulator of the PKR-SUMO non-covalent
      interaction as well as of the PKR SUMOylation. Finally, we show that the
      efficient SUMO-mediated eIF2alpha phosphorylation and inhibition of protein
      synthesis induced by PKR in response to dsRNA depend on this residue. In summary,
      our data identify a new mechanism of regulation of PKR activity and reinforce the
      relevance of both, tyrosine phosphorylation and SUMO interaction in controlling
      the activity of PKR.

PMID- 29070840
TI  - Chloropicophyceae, a new class of picophytoplanktonic prasinophytes.
AB  - Prasinophytes are a paraphyletic group of nine lineages of green microalgae that
      are currently classified either at the class or order level or as clades without
      formal taxonomic description. Prasinophyte clade VII comprises picoplanktonic
      algae that are important components of marine phytoplankton communities,
      particularly in moderately oligotrophic waters. Despite first being cultured in
      the 1960s, this clade has yet to be formally described. Previous phylogenetic
      analyses using the 18S rRNA gene divided prasinophyte clade VII into three
      lineages, termed A, B and C, the latter formed by a single species, Picocystis
      salinarum, that to date has only been found in saline lakes. Strains from
      lineages A and B cannot be distinguished by light microscopy and have very
      similar photosynthetic pigment profiles corresponding to the prasino-2A pigment
      group. We obtained phenotypic and genetic data on a large set of prasinophyte
      clade VII culture strains that allowed us to clarify the taxonomy of this
      important marine group. We describe two novel classes, the Picocystophyceae and
      the Chloropicophyceae, the latter containing two novel genera, Chloropicon and
      Chloroparvula, and eight new species of marine picoplanktonic green algae.

PMID- 29070841
TI  - An ApiAP2 member regulates expression of clonally variant genes of the human
      malaria parasite Plasmodium falciparum.
AB  - Variegated surface antigen expression is key to chronic infection and
      pathogenesis of the human malaria parasite Plasmodium falciparum. This protozoan
      parasite expresses distinct surface molecules that are encoded by clonally
      variant gene families such as var, rif and stevor. The molecular mechanisms
      governing activation of individual members remain ill-defined. To investigate the
      molecular events of the initial transcriptional activation process we focused on
      a member of the apicomplexan ApiAP2 transcription factor family predicted to bind
      to the 5' upstream regions of the var gene family, AP2-exp (PF3D7_1466400).
      Viable AP2-exp mutant parasites rely on expressing no less than a short truncated
      protein including the N-terminal AP2 DNA-binding domain. RNA-seq analysis in
      mutant parasites revealed transcriptional changes in a subset of exported
      proteins encoded by clonally variant gene families. Upregulation of RIFINs and
      STEVORs was validated at the protein levels. In addition, morphological
      alterations were observed on the surface of the host cells infected by the
      mutants. This work points to a complex regulatory network of clonally variant
      gene families in which transcription of a subset of members is regulated by the
      same transcription factor. In addition, we highlight the importance of the non
      DNA binding AP2 domain in functional gene regulation.

PMID- 29070842
TI  - Enhanced larval supply and recruitment can replenish reef corals on degraded
      reefs.
AB  - Reef-building corals have essential roles in reef ecosystems but are highly
      susceptible to disturbances. Increasing anthropogenic disturbances are eroding
      coral community resilience, leading to declining reef ecosystem function and
      status globally. Successful reproduction and recruitment are essential for
      restoring coral populations but recruitment-limitation can constrain recovery. We
      supplied ~400,000 Acropora tenuis larvae in fine-mesh enclosures on each of four
      larval-enhancement plots, comprising natural reef substrata and ten settlement
      tiles, on degraded reef areas in the northwestern Philippines. Initial mean total
      settlement on tiles in larval-enhancement plots was high (255.3 +/- 68.6),
      whereas no larvae settled in natural control plots. Recruit survivorship began
      stabilising after five months, with juveniles becoming visible by eye at nine
      months. After three years a mean of 2.3 m-2 colonies survived within each larval
      enhancement plot. Most colonies grew rapidly (16.1 +/- 0.7 cm mean diameter) and
      spawned successfully at three years, thereby quickly re-establishing a breeding
      population. In contrast, natural recruitment failed to produce any new visible A.
      tenuis colonies. These results demonstrate that mass larval settlement can
      rapidly enhance recruitment and coral recovery on degraded reef areas, and
      provides an important option for active reef restoration where larval supply and
      recruitment success are limiting.

PMID- 29070844
TI  - Individual mobility promotes punishment in evolutionary public goods games.
AB  - In explaining the pressing issue in biology and social sciences how cooperation
      emerges in a population of self-interested individuals, researchers recently pay
      intensive attentions to the role altruistic punishment plays. However, as higher
      order cooperators, survival of punishers is puzzling due to their extra cost in
      regulating norm violators. Previous works have highlighted the importance of
      individual mobility in promoting cooperation. Yet its effect on punishers remains
      to be explored. In this work we incorporate this feature into modeling the
      behavior of punishers, who are endowed with a choice between leaving current
      place or staying and punishing defectors. Results indicate that optimal mobility
      level of punishers is closely related to the cost of punishing. For considerably
      large cost, there exists medium tendency of migration which favors the survival
      of punishers. This holds for both the direct competition between punishers and
      defectors and the case where cooperators are involved, and can also be observed
      when various types of punishers with different mobility tendencies fight against
      defectors simultaneously. For cheap punishment, mobility does not provide with
      punishers more advantage even when they are initially rare. We hope our work
      provide more insight into understanding the role individual mobility plays in
      promoting public cooperation.

PMID- 29070843
TI  - Characterization of histone acylations links chromatin modifications with
      metabolism.
AB  - Over the last decade, numerous histone acyl post-translational modifications
      (acyl-PTMs) have been discovered, of which the functional significance is still
      under intense study. Here, we use high-resolution mass spectrometry to accurately
      quantify eight acyl-PTMs in vivo and after in vitro enzymatic assays. We assess
      the ability of seven histone acetyltransferases (HATs) to catalyze acylations on
      histones in vitro using short-chain acyl-CoA donors, proving that they are less
      efficient towards larger acyl-CoAs. We also observe that acyl-CoAs can acylate
      histones through non-enzymatic mechanisms. Using integrated metabolomic and
      proteomic approaches, we achieve high correlation (R 2 > 0.99) between the
      abundance of acyl-CoAs and their corresponding acyl-PTMs. Moreover, we observe a
      dose-dependent increase in histone acyl-PTM abundances in response to acyl-CoA
      supplementation in in nucleo reactions. This study represents a comprehensive
      profiling of scarcely investigated low-abundance histone marks, revealing that
      concentrations of acyl-CoAs affect histone acyl-PTM abundances by both enzymatic
      and non-enzymatic mechanisms.

PMID- 29070845
TI  - Maximizing T c by tuning nematicity and magnetism in FeSe1-x S x superconductors.
AB  - A fundamental issue concerning iron-based superconductivity is the roles of
      electronic nematicity and magnetism in realising high transition temperature (T
      c). To address this issue, FeSe is a key material, as it exhibits a unique
      pressure phase diagram involving non-magnetic nematic and pressure-induced
      antiferromagnetic ordered phases. However, as these two phases in FeSe have
      considerable overlap, how each order affects superconductivity remains
      perplexing. Here we construct the three-dimensional electronic phase diagram,
      temperature (T) against pressure (P) and isovalent S-substitution (x), for FeSe1
      x S x . By simultaneously tuning chemical and physical pressures, against which
      the chalcogen height shows a contrasting variation, we achieve a complete
      separation of nematic and antiferromagnetic phases. In between, an extended non
      magnetic tetragonal phase emerges, where T c shows a striking enhancement. The
      completed phase diagram uncovers that high-T c superconductivity lies near both
      ends of the dome-shaped antiferromagnetic phase, whereas T c remains low near the
      nematic critical point.

PMID- 29070846
TI  - A deterministic quantum dot micropillar single photon source with >65% extraction
      efficiency based on fluorescence imaging method.
AB  - We report optical positioning of single quantum dots (QDs) in planar distributed
      Bragg reflector (DBR) cavity with an average position uncertainty of ~20 nm using
      an optimized photoluminescence imaging method. We create single-photon sources
      based on these QDs in determined micropillar cavities. The brightness of the QD
      fluorescence is greatly enhanced on resonance with the fundamental mode of the
      cavity, leading to an high extraction efficiency of 68% +/- 6% into a lens with
      numerical aperture of 0.65, and simultaneously exhibiting low multi-photon
      probability (g(2)(0) = 0.144 +/- 0.012) at this collection efficiency.

PMID- 29070847
TI  - Compressive Volumetric Light-Field Excitation.
AB  - We explain how volumetric light-field excitation can be converted to a process
      that entirely avoids 3D reconstruction, deconvolution, and calibration of optical
      elements while taking scattering in the probe better into account. For spatially
      static probes, this is achieved by an efficient (one-time) light-transport
      sampling and light-field factorization. Individual probe particles (and arbitrary
      combinations thereof) can subsequently be excited in a dynamically controlled way
      while still supporting volumetric reconstruction of the entire probe in real-time
      based on a single light-field recording.

PMID- 29070848
TI  - Towards lead-free perovskite photovoltaics and optoelectronics by ab-initio
      simulations.
AB  - Lead (Pb) free non-toxic perovskite solar cells have become more important in the
      commercialization of the photovoltaic devices. In this study the structural,
      electronic, optical and mechanical properties of Pb-free inorganic metal halide
      cubic perovskites CsBX3 (B = Sn, Ge; X = I, Br, Cl) for perovskite solar cells
      are simulated using first-principles Density Functional Theory (DFT). These
      compounds are semiconductors with direct band gap energy and mechanically stable.
      Results suggest that the materials have high absorption coefficient, low
      reflectivity and high optical conductivity with potential application in solar
      cells and other optoelectronic energy devices. On the basis of the optical
      properties, one can expect that the Germanium (Ge) would be a better replacement
      of Pb as Ge containing compounds have higher optical absorption and optical
      conductivity than that of Pb containing compounds. A combinational analysis of
      the electronic, optical and mechanical properties of the compounds suggests that
      CsGeI3 based perovskite is the best Pb-free inorganic metal halide semiconductor
      for the solar cell application. However, the compound with solid solution of
      CsGe(I0.7Br0.3)3 is found to be mechanically more ductile than CsGeI3. This study
      will also guide to obtain Pb-free organic perovskites for optoelectronic devices.

PMID- 29070850
TI  - Tuning methane decomposition on stepped Ni surface: The role of subsurface atoms
      in catalyst design.
AB  - The decomposition of methane (CH4) is a catalytically important reaction in the
      production of syngas that is used to make a wide spectrum of hydrocarbons and
      alcohols, and a principal carbon deposition pathway in methane reforming.
      Literatures suggest that stepped Ni surface is uniquely selective toward methane
      decomposition to atomic C, contrary to other catalysts that favor the CH
      fragment. In this paper, we used dispersion-corrected density functional theory
      based first principles calculations to identify the electronic factors that
      govern this interesting property of stepped Ni surface. We found that the
      adsorption of atomic C on this surface is uniquely characterized by a 5
      coordinated bonding of C with Ni atoms from both the surface and subsurface
      layers. Comparison with Ru surface indicates the importance of the subsurface
      atoms of stepped Ni surface on its selectivity toward methane decomposition to
      atomic C. Interestingly, we found that substituting these subsurface atoms with
      other elements can dramatically change the reaction mechanism of methane
      decomposition, suggesting a new approach to catalyst design for hydrocarbon
      reforming applications.

PMID- 29070849
TI  - High-risk follicular lymphomas harbour more somatic mutations including those in
      the AID-motif.
AB  - We investigated clinical and genetic characteristics of high-risk follicular
      lymphoma (FL), that lacked evidence of large cell transformation at diagnosis, in
      the rituximab era. First, we retrospectively analysed the clinical features of
      100 patients with non-transformed FL that were consecutively treated with
      rituximab-containing therapies in a discovery cohort. The presence of either
      peripheral blood and/or bone involvement was associated with short progression
      free survival. This was confirmed in a validation cohort of 66 FL patients. Then,
      whole exome sequencing was performed on randomly selected 5 high- and 9 standard
      risk FL tumours. The most common mutational signature was a CG > TG substitution
      enriched signature associated with spontaneous deamination of 5-methylcytosine at
      CpG, but mutations in WA and WRC(Y) motifs (so-called activation-induced cytidine
      deaminase (AID) motifs) were also enriched throughout the whole exome. We found
      clustered mutations in target sequences of AID in the IG and BCL2 loci.
      Importantly, high-risk FLs harboured more somatic mutations (mean 190 vs. 138, P
      = 0.04), including mutations in WA (33 vs. 22, P = 0.038), WRC (34 vs. 22, P =
      0.016) and WRCY motifs (17 vs. 11, P = 0.004). These results suggest that genomic
      instability that allows for emergence of distinct mutations through AID activity
      underlies development of the high-risk FL phenotype.

PMID- 29070852
TI  - Impact of anesthetic agents on overall and recurrence-free survival in patients
      undergoing esophageal cancer surgery: A retrospective observational study.
AB  - Given that surgical stress response and surgical excision may increase the
      likelihood of post-surgery cancer dissemination and metastasis, the appropriate
      choice of surgical anesthetics may be important for oncologic outcomes. We
      evaluated the association of anesthetics used for general anesthesia with overall
      survival and recurrence-free survival in patients who underwent esophageal cancer
      surgery. Adult patients (922) underwent elective esophageal cancer surgery were
      included. The patients were divided into two groups according to the anesthetics
      administered during surgery: volatile anesthesia (VA) or intravenous anesthesia
      with propofol (TIVA). Propensity score and Cox regression analyses were
      performed. There were 191 patients in the VA group and 731 in the TIVA group. In
      the entire cohort, VA was independently associated with worse overall survival
      (HR 1.58; 95% CI 1.24-2.01; P < 0.001) and recurrence-free survival (HR 1.42; 95%
      CI 1.12-1.79; P = 0.003) after multivariable analysis adjustment. Similarly, in
      the propensity score matched cohorts, VA was associated with worse overall
      survival (HR 1.45; 95% CI 1.11-1.89; P = 0.006) and recurrence-free survival (HR
      1.44; 95% CI 1.11-1.87; P = 0.006). TIVA during esophageal cancer surgery was
      associated with better postoperative survival rates compared with volatile
      anesthesia.

PMID- 29070851
TI  - Association of leisure time physical activity and NMR-detected circulating amino
      acids in peripubertal girls: A 7.5-year longitudinal study.
AB  - This study investigated the longitudinal associations of physical activity and
      circulating amino acids concentration in peripubertal girls. Three hundred ninety
      six Finnish girls participated in the longitudinal study from childhood (mean age
      11.2 years) to early adulthood (mean age 18.2 years). Circulating amino acids
      were assessed by nuclear magnetic resonance spectroscopy. LTPA was assessed by
      self-administered questionnaire. We found that isoleucine, leucine and tyrosine
      levels were significantly higher in individuals with lower LTPA than their peers
      at age 11 (p < 0.05 for all), independent of BMI. In addition, isoleucine and
      leucine levels increased significantly (~15%) from childhood to early adulthood
      among the individuals with consistently low LTPA (p < 0.05 for both), while among
      the individuals with consistently high LTPA the level of these amino acids
      remained virtually unchanged. In conclusion, high level of physical activity is
      associated lower serum isoleucine and leucine in peripubertal girls, independent
      of BMI, which may serve as a mechanistic link between high level of physical
      activity in childhood and its health benefits later in life. Further studies in
      peripubertal boys are needed to assess whether associations between physical
      activity and circulating amino acids in children adolescents are sex-specific.

PMID- 29070853
TI  - Evaluation of Ga-DOTA-(D-Asp)n as bone imaging agents: D-aspartic acid peptides
      as carriers to bone.
AB  - 67Ga-DOTA-(L-Asp)11 and 67Ga-DOTA-(L-Asp)14, which have been developed as bone
      imaging agents, showed a high accumulation in bone and a rapid blood clearance in
      mice. However, peptides composed of D-amino acids are more stable in vivo than
      those composed of their L-equivalents. In this study, 67Ga-DOTA-(D-Asp)n (n = 2,
      5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology
      and evaluated. In hydroxyapatite binding assay, binding of 67Ga-DOTA-(D-Asp)n
      tended to increase with increasing length of the amino acid chain. 67Ga-DOTA-(D
      Asp)11 and 67Ga-DOTA-(D-Asp)14 caused a high accumulation of radioactivity in the
      bones of the mice. However, the results for 67Ga-DOTA-(D-Asp)n and 67Ga-DOTA-(L
      Asp)n were comparable. In urine analyses, the proportion of intact complex after
      injection of 67Ga-DOTA-(D-Asp)14 was significantly higher than that of 67Ga-DOTA
      (L-Asp)14. Although 67Ga-DOTA-(D-Asp)14 was more stable than 67Ga-DOTA-(L-Asp)14,
      the properties of 67Ga-DOTA-(D-Asp)n and 67Ga-DOTA-(L-Asp)n as bone imaging
      agents may be comparable.

PMID- 29070854
TI  - Altered Norbin Expression in Patients with Epilepsy and a Rat Model.
AB  - Norbin is widely distributed in neuronal tissues, is a regulator of
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation. Norbin is
      also an important endogenous modulator of metabotropic glutamate receptor 5
      (mGluR5) signaling, and nervous system-specific homozygous gene disruptions,
      result in epileptic seizures. In this study, we aimed to investigate norbin
      expression patterns in epilepsy and to elucidate the relationships between norbin
      and mGluR5 and p-CaMKII in epilepsy. Double-immunolabeling, immunohistochemistry
      and immunoblotting studies showed that norbin was downregulated in the temporal
      neocortex of patients with temporal lobe epilepsy (TLE) compared with control
      subjects. Moreover, in a rat model of lithium chloride-pilocarpine-induced
      epilepsy, norbin expression began to decrease at 6 h after the onset of status
      epilepticus and remained at a low level until 60 days. In addition, p-CaMKII
      expression was significantly increased in both patients with TLE and in animal
      model. Norbin and mGluR5 were found to be co-expressed in neurons of epileptic
      tissues. Finally, norbin over-expression facilitated by injections of adeno
      associated viral vector into the rat hippocampus increased latency and survival
      in the lithium chloride-pilocarpine model. Thus, our results indicate norbin
      participates in the pathogenesis of epilepsy, perhaps by modulating mGluR5
      signaling, regulating CaMKII phosphorylation, and may exert antiepileptic
      effects.

PMID- 29070855
TI  - Cooling combined with hyperoxic CO2 anesthesia is effective in improving the air
      exposure duration of tilapia.
AB  - Tilapia were subjected to cooling (CO, a stepwise reduction in temperature from
      30  degrees C to 15  degrees C), anesthesia (AN, anesthetized by hyperoxic carbon
      dioxide), air exposure (AE, exposed to air) and cold tolerance (CT, in 15 
      degrees C water) treatments, and the physiological responses were determined
      after the treatments. CO followed by AN treatment for tilapia could meet the
      criteria of an ideal anesthetic. Fish were deeply sedated within 69 s, completely
      anesthetized within 276 s and recovered within 308 s without any mortality. The
      stress responses induced by the CO&AN treatment were mild, whereas they were
      consistently increased in the AE treatment. Furthermore, the AE treatment caused
      tissue damage. The AE duration was significantly improved by CO&AN treatment, and
      the survival time of the CO&AE, AN&AE and CO&AN&AE treatments were 313 min, 351
      min and 561 min, respectively, in the laboratory experiments, whereas the
      survival rate of the CO&AN&AE treatment group after 240-min air exposure was
      95.2% in the pilot test. It appeared that cooling followed by hyperoxic CO2
      anesthesia would be suitable for handling tilapia in a short-time air exposure
      procedure.

PMID- 29070856
TI  - Directional mass transport in an atmospheric pressure surface barrier discharge.
AB  - In an atmospheric pressure surface barrier discharge the inherent physical
      separation between the plasma generation region and downstream point of
      application reduces the flux of reactive chemical species reaching the sample,
      potentially limiting application efficacy. This contribution explores the impact
      of manipulating the phase angle of the applied voltage to exert a level of
      control over the electrohydrodynamic forces generated by the plasma. As these
      forces produce a convective flow which is the primary mechanism of species
      transport, the technique facilitates the targeted delivery of reactive species to
      a downstream point without compromising the underpinning species generation
      mechanisms. Particle Imaging Velocimetry measurements are used to demonstrate
      that a phase shift between sinusoidal voltages applied to adjacent electrodes in
      a surface barrier discharge results in a significant deviation in the direction
      of the plasma induced gas flow. Using a two-dimensional numerical air plasma
      model, it is shown that the phase shift impacts the spatial distribution of the
      deposited charge on the dielectric surface between the adjacent electrodes. The
      modified surface charge distribution reduces the propagation length of the
      discharge ignited on the lagging electrode, causing an imbalance in the generated
      forces and consequently a variation in the direction of the resulting gas flow.

PMID- 29070857
TI  - Structure determination and activity manipulation of the turfgrass ABA receptor
      FePYR1.
AB  - Turfgrass are widely cultivated ornamental plants that have important ecological,
      societal and economical values. However, many turfgrass species are susceptible
      to drought and demand frequent irrigation thus consuming large amounts of water.
      With the ultimate goal of improving drought resistance in turfgrass, we
      identified several ABA receptors in turfgrass that are important to mediate ABA
      signaling and drought stress response. The ABA receptor FePYR1 from turfgrass
      Festuca elata was demonstrated to bind ABA as a monomer. Crystal structure
      analysis revealed that FePYR1 recognizes and binds ABA by the common gate-latch
      lock mechanism resembling the Arabidopsis ABA receptors, but the ABA binding
      pocket in FePYR1 shows discrepant residues resulting in different binding
      affinity to ABA. Structure-guided alterations of amino acid residues in FePYR1
      generated ABA receptor variants with significantly increased ABA binding
      affinity. Expression of FePYR1 in Arabidopsis conferred enhanced drought
      resistance in the transgenic plants. These findings provided detailed information
      about FePYR1 and demonstrated that structure-assisted engineering could create
      superior ABA receptors for improving plant drought resistance. The detailed
      structural information of FePYR1 would also assist future rational design of
      small molecules targeting specific ABA receptors in economically important plant
      species.

PMID- 29070859
TI  - Revealing the day-to-day regularity of urban congestion patterns with 3D speed
      maps.
AB  - In this paper, we investigate the day-to-day regularity of urban congestion
      patterns. We first partition link speed data every 10 min into 3D clusters that
      propose a parsimonious sketch of the congestion pulse. We then gather days with
      similar patterns and use consensus clustering methods to produce a unique global
      pattern that fits multiple days, uncovering the day-to-day regularity. We show
      that the network of Amsterdam over 35 days can be synthesized into only 4
      consensual 3D speed maps with 9 clusters. This paves the way for a cutting-edge
      systematic method for travel time predictions in cities. By matching the current
      observation to historical consensual 3D speed maps, we design an efficient real
      time method that successfully predicts 84% trips travel times with an error
      margin below 25%. The new concept of consensual 3D speed maps allows us to
      extract the essence out of large amounts of link speed observations and as a
      result reveals a global and previously mostly hidden picture of traffic dynamics
      at the whole city scale, which may be more regular and predictable than expected.

PMID- 29070858
TI  - Soloxolone methyl inhibits influenza virus replication and reduces virus-induced
      lung inflammation.
AB  - Highly pathogenic influenza viruses pose a serious public health threat to
      humans. Although vaccines are available, new antivirals are needed to efficiently
      control disease progression and virus transmission due to the emergence of drug
      resistant viral strains. In this study, we describe the anti-viral properties of
      Soloxolone methyl (SM) (methyl 2-cyano-3,12-dioxo-18betaH-olean-9(11),1(2)-dien
      30-oate, a chemical derivative of glycyrrhetinic acid) against the flu virus.
      Anti-flu efficacy studies revealed that SM exhibits antiviral activity against
      the H1N1 influenza A virus in a dose-dependent manner causing a more than 10-fold
      decrease in virus titer and a reduction in the expression of NP and M2 viral
      proteins. In a time-of-addition study, SM was found to act at an early stage of
      infection to exhibit an inhibitory effect on both the attachment step and virus
      uptake into cells. Also, in infected cells SM downregulates the expression of the
      inflammatory cytokines IL-6 and TNF-alpha. In infected mice, SM administered
      intranasally prior to and after infection significantly decreases virus titers in
      the lung and prevents post-challenge pneumonia. Together, these results suggest
      that Soloxolone methyl might serve as an effective therapeutic agent to manage
      influenza outbreaks and virus-associated complications, and further preclinical
      and clinical investigation may be warranted.

PMID- 29070861
TI  - Pillared graphene as an ultra-high sensitivity mass sensor.
AB  - Hybrid structure of graphene sheets supported by carbon nanotubes (CNTs) sustains
      unique properties of both graphene and CNTs, which enables the utilization of
      advantages of the two novel materials. In this work, the capability of three
      dimensional pillared graphene structure used as nanomechanical sensors is
      investigated by performing molecular dynamics simulations. The obtained results
      demonstrate that: (a) the mass sensitivity of the pillared graphene structure is
      ultrahigh and can reach at least 1 yg (10-24 g) with a mass responsivity 0.34 GHz
      . yg-1; (b) the sizes of pillared graphene structure, particularly the distance
      between carbon nanotube pillars, have a significant effect on the sensing
      performance; (c) an analytical expression can be derived to detect the deposited
      mass from the resonant frequency of the pillared graphene structure. The
      performed analyses might be significant to future design and application of
      pillared graphene based sensors with high sensitivity and large detecting area.

PMID- 29070860
TI  - Vacancy-induced brittle to ductile transition of W-M co-doped Al3Ti (M=Si, Ge, Sn
      and Pb).
AB  - We investigated the effect of vacancy formation on brittle (D022) to ductile (L12
      like) transition in Al3Ti using DFT calculations. The well-known pseudogap on the
      density of states of Al3Ti migrates towards its Fermi level from far above, via a
      W - M co-doping strategy, where M is Si, Ge, Sn or Pb respectively. In
      particular, by a W - M co-doping the underline electronic structure of the
      pseudogap approaches an octahedral (L12: t2g, eg) from the tetragonal (D022: eg,
      b2g, a1g, b1g) crystal field. Our calculations demonstrated that (1) a W-doping
      is responsible for the close up of the energy gap between a1g and b1g so that
      they tend to merge into an eg symmetry, and (2) all M-doping lead to a narrower
      gap between eg and b2g (moving towards a t2g symmetry). Thus, a brittle to
      ductile transition in Al3Ti is possible by adopting this W - M co-doping
      strategy. We further recommend the use of W-Pb co-doped Al3Ti to replace the less
      anodic Al electrode in Al-battery, due to its improved ductility and high Al
      diffusivity. Finally this study opens a new field in physics to tailor mechanical
      properties by manipulating electron energy level(s) towards higher symmetry via
      vacancy optimization.

PMID- 29070862
TI  - Persistent homology index as a robust quantitative measure of immunohistochemical
      scoring.
AB  - Immunohistochemical data (IHC) plays an important role in clinical practice, and
      is typically gathered in a semi-quantitative fashion that relies on some degree
      of visual scoring. However, visual scoring by a pathologist is inherently
      subjective and manifests both intra-observer and inter-observer variability. In
      this study, we introduce a novel computer-aided quantification methodology for
      immunohistochemical scoring that uses the algebraic concept of persistent
      homology. Using 8 bit grayscale image data derived from 90 specimens of invasive
      ductal carcinoma of the breast, stained for the replicative marker Ki-67, we
      computed homology classes. These were then compared to nuclear grades and the Ki
      67 labeling indices obtained by visual scoring. Three metrics for IHC staining
      were newly defined: Persistent Homology Index (PHI), center coordinates of
      positive and negative groups, and the sum of squares within groups (WSS). This
      study demonstrates that PHI, a novel index for immunohistochemical labeling using
      persistent homology, can produce highly similar data to that generated by a
      pathologist using visual evaluation. The potential benefits associated with our
      novel technology include both improved quantification and reproducibility. Since
      our method reflects cellularity and nuclear atypia, it carries a greater quantity
      of biologic data compared to conventional evaluation using Ki-67.

PMID- 29070863
TI  - PARP1-produced poly-ADP-ribose causes the PARP12 translocation to stress granules
      and impairment of Golgi complex functions.
AB  - Poly-ADP-ribose-polymerases (PARPs) 1 and 2 are nuclear enzymes that catalyze the
      poly-ADP-ribosylation of nuclear proteins transferring poly-ADP-ribose (PAR)
      polymers to specific residues. PARPs and PAR intervene in diverse functions,
      including DNA repair in the nucleus and stress granule assembly in the cytoplasm.
      Stress granules contribute to the regulation of translation by clustering and
      stabilizing mRNAs as well as several cytosolic PARPs and signaling proteins to
      modulate cell metabolism and survival. Our study is focused on one of these
      PARPs, PARP12, a Golgi-localized mono-ADP-ribosyltransferase that under stress
      challenge reversibly translocates from the Golgi complex to stress granules.
      PARP1 activation and release of nuclear PAR drive this translocation by direct
      PAR binding to the PARP12-WWE domain. Thus, PAR formation functionally links the
      activity of the nuclear and cytosolic PARPs during stress response, determining
      the release of PARP12 from the Golgi complex and the disassembly of the Golgi
      membranes, followed by a block in anterograde-membrane traffic. Notably, these
      functions can be rescued by reverting the stress condition (by drug wash-out).
      Altogether these data point at a novel, reversible nuclear signaling that senses
      stress to then act on cytosolic PARP12, which in turn converts the stress
      response into a reversible block in intracellular-membrane traffic.

PMID- 29070864
TI  - Plasmonic nanohole array for enhancing the SERS signal of a single layer of
      graphene in water.
AB  - We numerically design and experimentally test a SERS-active substrate for
      enhancing the SERS signal of a single layer of graphene (SLG) in water. The SLG
      is placed on top of an array of silver-covered nanoholes in a polymer and is
      covered with water. Here we report a large enhancement of up to 2 * 105 in the
      SERS signal of the SLG on the patterned plasmonic nanostructure for a 532 nm
      excitation laser wavelength. We provide a detailed study of the light-graphene
      interactions by investigating the optical absorption in the SLG, the density of
      optical states at the location of the SLG, and the extraction efficiency of the
      SERS signal of the SLG. Our numerical calculations of both the excitation field
      and the emission rate enhancements support the experimental results. We find that
      the enhancement is due to the increase in the confinement of electromagnetic
      fields on the location of the SLG that results in enhanced light absorption in
      the graphene at the excitation wavelength. We also find that water droplets
      increase the density of optical radiative states at the location of the SLG,
      leading to enhanced spontaneous emission rate of graphene at its Raman emission
      wavelengths.

PMID- 29070865
TI  - Transparent and 'opaque' conducting electrodes for ultra-thin highly-efficient
      near-field thermophotovoltaic cells.
AB  - Transparent conducting electrodes play a fundamental role in far-field
      PhotoVoltaic systems, but have never been thoroughly investigated for near-field
      applications. Here we show, in the context of near-field planar ultra-thin
      ThermoPhotoVoltaic cells using surface-plasmon-polariton thermal emitters, that
      the resonant nature of the nanophotonic system significantly alters the design
      criteria for the necessary conducting front electrode. The traditional ratio of
      optical-to-DC conductivities is alone not an adequate figure of merit, instead
      the desired impedance matching between the emitter and absorber modes along with
      their coupling to the free-carrier resonance of the front electrode are key for
      optimal device design and performance. Moreover, we demonstrate that conducting
      electrodes 'opaque' to incoming far-field radiation can, in fact, be used in the
      near field with decent performance by taking advantage of evanescent photon
      tunneling from the emitter to the absorber. Finally, we identify and compare
      appropriate tunable-by-doping materials for front electrodes in near-field
      ThermoPhotoVoltaics, specifically molybdenum-doped indium oxide, dysprosium-doped
      cadmium oxide, graphene and diffused semiconductors, but also for 'opaque'
      electrodes, tin-doped indium oxide and silver nano-films. Predicted estimated
      performances include output power density ~10 W/cm 2 with >45% efficiency at 2100
      degrees K emitter temperature and 60 Omega electrode square resistance, thus
      increasing the promise for high-performance practical devices.

PMID- 29070866
TI  - Dominant control of agriculture and irrigation on urban heat island in India.
AB  - As is true in many regions, India experiences surface Urban Heat Island (UHI)
      effect that is well understood, but the causes of the more recently discovered
      Urban Cool Island (UCI) effect remain poorly constrained. This raises questions
      about our fundamental understanding of the drivers of rural-urban environmental
      gradients and hinders development of effective strategies for mitigation and
      adaptation to projected heat stress increases in rapidly urbanizing India. Here
      we show that more than 60% of Indian urban areas are observed to experience a day
      time UCI. We use satellite observations and the Community Land Model (CLM) to
      identify the impact of irrigation and prove for the first time that UCI is caused
      by lack of vegetation and moisture in non-urban areas relative to cities. In
      contrast, urban areas in extensively irrigated landscapes generally experience
      the expected positive UHI effect. At night, UHI warming intensifies, occurring
      across a majority (90%) of India's urban areas. The magnitude of rural-urban
      temperature contrasts is largely controlled by agriculture and moisture
      availability from irrigation, but further analysis of model results indicate an
      important role for atmospheric aerosols. Thus both land-use decisions and
      aerosols are important factors governing, modulating, and even reversing the
      expected urban-rural temperature gradients.

PMID- 29070867
TI  - Electrically-driven single-photon sources based on colloidal quantum dots with
      near-optimal antibunching at room temperature.
AB  - Photonic quantum information requires high-purity, easily accessible, and
      scalable single-photon sources. Here, we report an electrically driven single
      photon source based on colloidal quantum dots. Our solution-processed devices
      consist of isolated CdSe/CdS core/shell quantum dots sparsely buried in an
      insulating layer that is sandwiched between electron-transport and hole-transport
      layers. The devices generate single photons with near-optimal antibunching at
      room temperature, i.e., with a second-order temporal correlation function at zero
      delay (g (2)(0)) being <0.05 for the best devices without any spectral filtering
      or background correction. The optimal g (2)(0) from single-dot
      electroluminescence breaks the lower g (2)(0) limit of the corresponding single
      dot photoluminescence. Such highly suppressed multi-photon-emission probability
      is attributed to both novel device design and carrier injection/recombination
      dynamics. The device structure prevents background electroluminescence while
      offering efficient single-dot electroluminescence. A quantitative model is
      developed to illustrate the carrier injection/recombination dynamics of single
      dot electroluminescence.

PMID- 29070868
TI  - Nonreciprocal light propagation in coupled microcavities system beyond weak
      excitation approximation.
AB  - We propose a scheme for nonreciprocal light propagation in two coupled cavities
      system, in which a two-level quantum emitter is coupled to one of the optical
      microcavities. For the case of parity-time ([Formula: see text]) symmetric system
      (i.e., coupled active-passive cavities system), the cavity gain can significantly
      enhance the optical nonlinearity induced by the interaction between a quantum
      emitter and cavity field beyond weak-excitation approximation. The increased
      optical nonlinearity results in the non-lossy nonreciprocal light propagation
      with high isolation ratio in proper parameters range. In addition, our
      calculations show that nonreciprocal light propagation will not be affected by
      the unstable output field intensity caused by optical bistability, and we can
      even switch directions of nonreciprocal light propagation by appropriately
      adjusting the system parameters.

PMID- 29070869
TI  - Long tailed trions in monolayer MoS2: Temperature dependent asymmetry and
      resulting red-shift of trion photoluminescence spectra.
AB  - Monolayer molybdenum disulfide (MoS2) has emerged as a model system for studying
      many-body physics because the low dimensionality reduces screening leading to
      tightly bound states stable at room temperature. Further, the many-body states
      possess a pseudo-spin degree of freedom that corresponds with the two direct-gap
      valleys of the band structure, which can be optically manipulated. Here we focus
      on one bound state, the negatively charged trion. Unlike excitons, trions can
      radiatively decay with non-zero momentum by kicking out an electron, resulting in
      an asymmetric trion photoluminescence (PL) peak with a long low-energy tail and
      peak position that differs from the zero momentum trion energy. The asymmetry of
      the trion PL peak and resulting peak red-shift depends both on the trion size and
      a temperature-dependent contribution. Ignoring the trion asymmetry will result in
      over estimating the trion binding energy by nearly 20 meV at room temperature. We
      analyze the temperature-dependent PL to reveal the effective trion size,
      consistent with the literature, and the temperature dependence of the band gap
      and spin-orbit splitting of the valence band. This is the first time the
      temperature-dependence of the trion PL has been analyzed with such detail in any
      system.

PMID- 29070870
TI  - Optical properties, spectral, and lifetime measurements of central nervous system
      tumors in humans.
AB  - A key challenge of central nervous system tumor surgery is to discriminate
      between brain regions infiltrated by tumor cells and surrounding healthy tissue.
      Although monitoring of autofluorescence could potentially be an efficient way to
      provide reliable information for these regions, we found little information on
      this subject, and thus we conducted studies of brain tissue optical properties.
      This particular study focuses on the different optical quantitative responses of
      human central nervous system tumors and their corresponding controls.
      Measurements were performed on different fixed human tumoral and healthy brain
      samples. Four groups of central nervous system tumors (glioblastoma, diffuse
      glioma, meningioma and metastasis) were discriminated from healthy brain and
      meninx control tissues. A threshold value was found for the scattering and
      absorption coefficient between tumoral and healthy groups. Emission Spectra of
      healthy tissue had a significant higher intensity than tumoral groups. The redox
      and optical index ratio were thenn calculated and these also showed significant
      discrimination. Two fluorescent molecules, NADH and porphyrins, showed distinct
      lifetim values among the different groups of samples. This study defines several
      optical indexes that can act as combinated indicators to discriminate healthy
      from tumoral tissues.

PMID- 29070871
TI  - Implementation of cascade logic gates and majority logic gate on a simple and
      universal molecular platform.
AB  - Wiring a series of simple logic gates to process complex data is significantly
      important and a large challenge for untraditional molecular computing systems.
      The programmable property of DNA endows its powerful application in molecular
      computing. In our investigation, it was found that DNA exhibits excellent
      peroxidase-like activity in a colorimetric system of TMB/H2O2/Hemin (TMB, 3,3',
      5,5'-Tetramethylbenzidine) in the presence of K+ and Cu2+, which is significantly
      inhibited by the addition of an antioxidant. According to the modulated catalytic
      activity of this DNA-based catalyst, three cascade logic gates including AND-OR
      INH (INHIBIT), AND-INH and OR-INH were successfully constructed. Interestingly,
      by only modulating the concentration of Cu2+, a majority logic gate with a single
      vote veto function was realized following the same threshold value as that of the
      cascade logic gates. The strategy is quite straightforward and versatile and
      provides an instructive method for constructing multiple logic gates on a simple
      platform to implement complex molecular computing.

PMID- 29070873
TI  - Interfacial Reactions in the Li/Si diffusion couples: Origin of Anisotropic
      Lithiation of Crystalline Si in Li-Si batteries.
AB  - As opposed to the common understanding that diffusion into a cubic-structured
      single crystal is independent of its crystalline orientation, the diffusion of Li
      to crystalline Si (c-Si) is anisotropic, which acts as the major cause for the
      fracture of Si anodes in Li-ion batteries. Here, by conducting
      comprehensive/multi-scale simulation studies based on molecular dynamics and
      density functional theory, we elucidate how and why Li diffusion in c-Si is
      anisotropic. We found that Li ions diffuse to c-Si by following a particular
      atomic-scale space corresponding to the lowest value of the valence orbital in c
      Si, causing Li ions to take a tortuous diffusion pathway. The degree of the
      tortuosity of the pathway differs depending on the crystallographic orientation
      of Si, and it acts as the major cause for anisotropic lithiation. We also develop
      a structural parameter that can quantitatively evaluate the orientation
      dependency of the lithiation of c-Si.

PMID- 29070872
TI  - Baf53a is involved in survival of mouse ES cells, which can be compensated by
      Baf53b.
AB  - The human Baf (Brg1/Brm associated factor) complex, also known as the mammalian
      SWI/SNF chromatin-remodeling complex, is involved in a variety of cellular
      processes. The pluripotency and self-renewal abilities are major characteristics
      of embryonic stem (ES) cells and are regulated by the ES cell-specific BAF
      (esBAF) complex. Baf53a is one of the subunits of the esBAF complex. Here, we
      found that Baf53a was expressed in undifferentiated ES cells and that it
      interacted with Oct3/4. Analyses of tetracycline-inducible Baf53a conditional
      knockout ES cells revealed that the undifferentiated markers, including Nanog and
      Oct3/4, were expressed in Baf53a-deficient ES cells; however, growth of the cells
      was repressed, and expression of p53, p21, and cleaved Caspase 3 was increased.
      Cell death of Baf53a-deficient ES cells was rescued by overexpression of Baf53a,
      but not by the Baf53a M3 mutant (E388A/R389A/R390A). Interestingly, Baf53b, a
      homologue of Baf53a, rescued cell death of Baf53a-deficient ES cells. Baf53a
      deficient ES cells overexpressing exogenous Baf53a or Baf53b remained in the
      undifferentiated state, proliferated, and repressed expression of p21. In
      summary, our findings suggest that Baf53a is involved in the survival of ES cells
      by regulating p53 and Caspase3, and that Baf53b is able to compensate for this
      functional aspect of Baf53a.

PMID- 29070874
TI  - Synergistic acceleration of experimental tooth movement by supplementary high
      frequency vibration applied with a static force in rats.
AB  - Several recent prospective clinical trials have investigated the effect of
      supplementary vibration applied with fixed appliances in an attempt to accelerate
      tooth movement and shorten the duration of orthodontic treatment. Among them,
      some studies reported an increase in the rate of tooth movement, but others did
      not. This technique is still controversial, and the underlying cellular and
      molecular mechanisms remain unclear. In the present study, we developed a new
      vibration device for a tooth movement model in rats, and investigated the
      efficacy and safety of the device when used with fixed appliances. The most
      effective level of supplementary vibration to accelerate tooth movement
      stimulated by a continuous static force was 3 gf at 70 Hz for 3 minutes once a
      week. Furthermore, at this optimum-magnitude, high-frequency vibration could
      synergistically enhance osteoclastogenesis and osteoclast function via NF-kappaB
      activation, leading to alveolar bone resorption and finally, accelerated tooth
      movement, but only when a static force was continuously applied to the teeth.
      These findings contribute to a better understanding of the mechanism by which
      optimum-magnitude high-frequency vibration accelerates tooth movement, and may
      lead to novel approaches for the safe and effective treatment of malocclusion.

PMID- 29070875
TI  - Transcriptome Analysis Reveals Neuroprotective aspects of Human Reactive
      Astrocytes induced by Interleukin 1beta.
AB  - Reactive astrogliosis is a critical process in neuropathological conditions and
      neurotrauma. Although it has been suggested that it confers neuroprotective
      effects, the exact genomic mechanism has not been explored. The prevailing dogma
      of the role of astrogliosis in inhibition of axonal regeneration has been
      challenged by recent findings in rodent model's spinal cord injury, demonstrating
      its neuroprotection and axonal regeneration properties. We examined whether their
      neuroprotective and axonal regeneration potentials can be identify in human
      spinal cord reactive astrocytes in vitro. Here, reactive astrogliosis was induced
      with IL1beta. Within 24 hours of IL1beta induction, astrocytes acquired reactive
      characteristics. Transcriptome analysis of over 40000 transcripts of genes and
      analysis with PFSnet subnetwork revealed upregulation of chemokines and axonal
      permissive factors including FGF2, BDNF, and NGF. In addition, most genes
      regulating axonal inhibitory molecules, including ROBO1 and ROBO2 were
      downregulated. There was no increase in the gene expression of "Chondroitin
      Sulfate Proteoglycans" (CSPGs') clusters. This suggests that reactive astrocytes
      may not be the main CSPG contributory factor in glial scar. PFSnet analysis also
      indicated an upregulation of "Axonal Guidance Signaling" pathway. Our result
      suggests that human spinal cord reactive astrocytes is potentially
      neuroprotective at an early onset of reactive astrogliosis.

PMID- 29070876
TI  - Late-onset Alzheimer's disease is associated with inherent changes in
      bioenergetics profiles.
AB  - Body-wide changes in bioenergetics, i.e., energy metabolism, occur in normal
      aging and disturbed bioenergetics may be an important contributing mechanism
      underlying late-onset Alzheimer's disease (LOAD). We investigated the
      bioenergetic profiles of fibroblasts from LOAD patients and healthy controls, as
      a function of age and disease. LOAD cells exhibited an impaired mitochondrial
      metabolic potential and an abnormal redox potential, associated with reduced
      nicotinamide adenine dinucleotide metabolism and altered citric acid cycle
      activity, but not with disease-specific changes in mitochondrial mass, production
      of reactive oxygen species, transmembrane instability, or DNA deletions. LOAD
      fibroblasts demonstrated a shift in energy production to glycolysis, despite an
      inability to increase glucose uptake in response to IGF-1. The increase of
      glycolysis and the abnormal mitochondrial metabolic potential in LOAD appeared to
      be inherent, as they were disease- and not age-specific. Our findings support the
      hypothesis that impairment in multiple interacting components of bioenergetic
      metabolism may be a key mechanism contributing to the risk and pathophysiology of
      LOAD.

PMID- 29070877
TI  - Probing Resistance Mutations in Retroviral Integrases by Direct Measurement of
      Dolutegravir Fluorescence.
AB  - FDA-approved integrase strand transfer inhibitors (raltegravir, elvitegravir and
      dolutegravir) efficiently inhibit HIV-1 replication. Here, we present
      fluorescence properties of these inhibitors. Dolutegravir displays an excitation
      mode particularly dependent on Mg2+ chelation, allowing to directly probe its
      Mg2+-dependent binding to the prototype foamy virus (PFV) integrase. Dolutegravir
      binding studied by both its fluorescence anisotropy and subsequent emission
      enhancement, strictly requires a preformed integrase/DNA complex, the ten
      terminal base pairs from the 3'-end of the DNA reactive strand being crucial to
      optimize dolutegravir-binding in the context of the ternary complex. From the
      protein side, mutation of any catalytic residue fully abolishes dolutegravir
      binding. We also compared dolutegravir-binding to PFV F190Y, G187R and S217K
      mutants, corresponding to HIV-1 F121Y, G118R and G140S/Q148K mutations that
      confer low-to-high resistance levels against raltegravir/dolutegravir. The
      dolutegravir-binding properties derived from fluorescence-based binding assays
      and drug susceptibilities in terms of catalytic activity, are well correlated.
      Indeed, dolutegravir-binding to wild-type and F190Y integrases are comparable
      while strongly compromised with G187R and S217K. Accordingly, the two latter
      mutants are highly resistant to dolutegravir while F190Y shows only moderate or
      no resistance. Intrinsic fluorescence properties of dolutegravir are thus
      particularly suitable for a thorough characterization of both DNA-binding
      properties of integrase and resistance mutations.

PMID- 29070878
TI  - The J-curve Association between Systolic Blood Pressure and Clinical Outcomes in
      Ischemic Stroke or TIA: The BOSS Study.
AB  - We aimed to assess the association between systolic blood pressure (SBP) and
      clinical outcome in 2,397 ischemic stroke (IS) or transient ischemic attack (TIA)
      patients from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke
      (BOSS) study. BOSS study was a hospital-based, prospective cohort study. The SBP
      was defined as mean value of 90 days self-measured SBP after onset. Cox
      proportional hazards models were conducted to test the risk of combined vascular
      events (CVE) and stroke recurrence among different SBP categories. Restricted
      cubic splines were used to explore the shape of associations between SBP and
      clinical outcomes. A J-shaped association of SBP with CVE and stroke recurrence
      within 90 days was observed (P nonlinearity < 0.001 for both). After adjusting
      for age, gender, medical history, atrial fibrillation, admission NHISS score, and
      secondary prevention. The hazard ratios (95% confidence intervals) of SBP <115
      and ?165 mmHg compared with 125-134 mmHg were 3.45 (1.11-10.66) and 7.20 (2.91
      17.80) for CVE, 2.68 (0.75-9.53) and 9.69 (3.86-24.35) for stroke recurrence,
      respectively. Similar J-shaped relationships were found after 1 year of follow
      up. In conclusion, both high and low SBP are associated with poor prognosis in
      this population.

PMID- 29070881
TI  - A numerical analysis of a magnetocaloric refrigerator with a 16-layer
      regenerator.
AB  - A numerical analysis was conducted to study a room temperature magnetocaloric
      refrigerator with a 16-layer parallel plates active magnetic regenerator (AMR).
      Sixteen layers of LaFeMnSiH having different Curie temperatures were employed as
      magnetocaloric material (MCM) in the regenerator. Measured properties data was
      used. A transient one dimensional (1D) model was employed, in which a unique
      numerical method was developed to significantly accelerate the simulation speed
      of the multi-layer AMR system. As a result, the computation speed of a multi
      layer AMR case was very close to the single-layer configuration. The performance
      of the 16-layer AMR system in different frequencies and utilizations has been
      investigated using this model. To optimize the layer length distribution of the
      16-layer MCMs in the regenerator, a set of 137 simulations with different MCM
      distributions based on the Design of Experiments (DoE) method was conducted and
      the results were analyzed. The results show that the 16-layer AMR system can
      operate up to 84% of Carnot cycle COP at a temperature span of 41 K, which cannot
      be obtained using an AMR with fewer layers. The DoE results indicate that for a
      16-layer AMR system, the uniform distribution is very close to the optimized
      design.

PMID- 29070880
TI  - Effect of adipose-derived mesenchymal stem cell transplantation on vascular
      calcification in rats with adenine-induced kidney disease.
AB  - Previous studies have investigated the use of mesenchymal stem cells (MSCs) to
      treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on
      vascular calcification in chronic kidney disease (CKD) is still poorly
      understood. In the present study, we explored the potential of ASCs for the
      treatment of CKD and vascular calcification. CKD was induced in male Sprague
      Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs
      transplantation significantly reduced serum inorganic phosphorus (Pi) as compared
      to that in the control. The histopathology of the kidneys showed a greater
      dilation of tubular lumens and interstitial fibrosis in the control group.
      Calcium and Pi contents of the aorta in the ASCs transplantation group were lower
      than those in the control group. Von Kossa staining of the thoracic aorta media
      revealed that ASCs transplantation suppressed vascular calcification. Thus, this
      study revealed that autogenic ASCs transplantation inhibits kidney damage and
      suppresses the progression of vascular calcification in the CKD rat model,
      suggesting that autogenic ASCs transplantation is a novel approach for preventing
      the progression of CKD and vascular calcification.

PMID- 29070879
TI  - Language learning in the adult brain: disrupting the dorsolateral prefrontal
      cortex facilitates word-form learning.
AB  - Adults do not learn languages as easily as children do. It has been hypothesized
      that the late-developing prefrontal cortex that supports executive functions
      competes with procedural learning mechanisms that are important for language
      learning. To address this hypothesis, we tested whether a temporary neural
      disruption of the left Dorsolateral Prefrontal Cortex (DLPFC) can improve
      implicit, procedural learning of word-forms in adults. Young adults were
      presented with repeating audio-visual sequences of syllables for immediate serial
      recall in a Hebb repetition learning task that simulates word-form learning.
      Inhibitory theta-burst Transcranial Magnetic Stimulation was applied to the left
      DLPFC or to the control site before the Hebb task. The DLPFC-disrupted group
      showed enhanced learning of the novel phonological sequences relative to the
      control group. Moreover, learning was negatively correlated with executive
      functions that rely on the DLPFC in the control group, but not in the DLPFC
      disrupted group. The results support the hypothesis that a mature prefrontal
      cortex competes with implicit learning of word-forms. The findings provide new
      insight into the competition between brain mechanisms that contribute to language
      learning in the adult brain.

PMID- 29070882
TI  - Hydration number: crucial role in nuclear magnetic relaxivity of Gd(III) chelate
      based nanoparticles.
AB  - Today, nanostructure-based contrast agents (CA) are emerging in the field of
      magnetic resonance imaging (MRI). Their sensitivity is reported as greatly
      improved in comparison to commercially used chelate-based ones. The present work
      is aimed at revealing the factors governing the efficiency of longitudinal
      magnetic relaxivity (r1) in aqueous colloids of core-shell Gd(III)-based
      nanoparticles. We report for the first time on hydration number (q) of
      gadolinium(III) as a substantial factor in controlling r1 values of
      polyelectrolyte-stabilized nanoparticles built from water insoluble complexes of
      Gd(III). The use of specific complex structure enables to reveal the impact of
      the inner-sphere hydration number on both r1 values for the Gd(III)-based
      nanoparticles and the photophysical properties of their luminescent Tb(III) and
      Eu(III) counterparts. The low hydration of TTA-based Gd(III) complexes (q ~ 1)
      agrees well with the poor relaxivity values (r1 = 2.82 mM-1s-1 and r2 = 3.95 mM
      1s-1), while these values tend to increase substantially (r1 = 12.41 mM-1s-1, r2
      = 14.36 mM-1s-1) for aqueous Gd(III)-based colloids, when macrocyclic 1,3
      diketonate is applied as the ligand (q ~ 3). The regularities obtained in this
      work are fundamental in understanding the efficiency of MRI probes in the fast
      growing field of nanoparticulate contrast agents.

PMID- 29070883
TI  - Combined immunotherapy with anti-PDL-1/PD-1 and anti-CD4 antibodies cures
      syngeneic disseminated neuroblastoma.
AB  - Anti-PD-1 or anti-PD-L1 blocking monoclonal antibodies (mAbs) have shown potent
      anti-tumor effects in adult cancer patients and clinical studies have recently
      been started in pediatric cancers, including high-risk/relapsing neuroblastoma
      (NB). Therefore, we studied the effects of anti-PD-1/PD-L1 mAbs in two syngeneic
      models of disseminated NB generated by the injection of either Neuro2a or NXS2
      cells, which express PD-L1. In addition, we tested the combination of these
      agents with the immune-enhancing cytokine IL-21, the Ecto-NTPDase inhibitor POM
      1, an anti-CD25 mAb targeting Treg cells, or an anti-CD4 mAb. We previously
      showed that CD4-transient depletion removes CD4+CD25+ Treg cells and other
      CD4+CD25- regulatory subsets. Here we show that mono-therapy with anti-PD-1/PD-L1
      mAbs had no effect on systemic NB progression in vivo, and also their combination
      with IL-21, POM-1 or anti-CD25 mAb was ineffective. The combined use of anti-PD-1
      with an anti-CD4 mAb mediated a very potent, CD8-dependent, synergistic effect
      leading to significant elongation of tumor-free survival of mice, complete tumor
      regression and durable anti-NB immunity. Similar results were obtained by
      combining the anti-PD-L1 and anti-CD4 mAbs. These findings indicate that both PD
      1/PD-L1 and CD4+ T cell-related immune-regulatory mechanisms must be
      simultaneously blocked to mediate therapeutic effects in these models.

PMID- 29070884
TI  - Telmisartan Activates PPARdelta to Improve Symptoms of Unpredictable Chronic Mild
      Stress-Induced Depression in Mice.
AB  - Major depression is a common mental disorder that has been established to be
      associated with a decrease in serotonin and/or serotonin transporters in the
      brain. Peroxisome proliferator-activated receptor delta (PPARdelta) has been
      introduced as a potential target for depression treatment. Telmisartan was
      recently shown to activate PPARdelta expression; therefore, the effectiveness of
      telmisartan in treating depression was investigated. In unpredictable chronic
      mild stress (UCMS) model, treatment with telmisartan for five weeks notably
      decrease in the time spent in the central and the reduced frequency of grooming
      and rearing in open filed test (OFT) and the decreased sucrose consumption in
      sucrose preference test (SPT) compared with the paradigms. Telmisartan also
      reversed the decrease in PPARdelta and 5-HTT levels in the hippocampus of
      depression-like mice. Administration of PPARdelta antagonist GSK0660 and direct
      infusion of sh-PPARdelta into the brain blocked the effects of telmisartan on the
      improvement of depression-like behavior in these mice. Moreover, telmisartan
      enhanced the expression of PPARdelta and 5HTT in H19-7 cells. In conclusion, the
      obtained results suggest that telmisartan improves symptoms of stress-induced
      depression in animals under chronic stress through activation of PPARdelta.
      Therefore, telmisartan may be developed as a potential anti-depressant in the
      future.

PMID- 29070885
TI  - Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1
      secretion in enteroendocrine cells and attenuates hyperglycemia in type 2
      diabetic mice.
AB  - Odorants are non-nutrients. However, they exist abundantly in foods, wines, and
      teas, and thus can be ingested along with the other nutrients during a meal.
      Here, we have focused on the chemical-recognition ability of these ORs and
      hypothesized that the odorants ingested during a meal may play a physiological
      role by activating the gut-expressed ORs. Using a human-derived enteroendocrine L
      cell line, we discovered the geraniol- and citronellal-mediated stimulation of
      glucagon-like peptide-1 (GLP-1) secretion and elucidated the corresponding
      cellular downstream signaling pathways. The geraniol-stimulated GLP-1 secretion
      event in the enteroendocrine cell line was mediated by the olfactory-type G
      protein, the activation of adenylyl cyclase, increased intracellular cAMP levels,
      and extracellular calcium influx. TaqMan qPCR demonstrated that two ORs
      corresponding to geraniol and citronellal were expressed in the human
      enteroendocrine cell line and in mouse intestinal specimen. In a type 2 diabetes
      mellitus mouse model (db/db), oral administration of geraniol improved glucose
      homeostasis by increasing plasma GLP-1 and insulin levels. This insulinotropic
      action of geraniol was GLP-1 receptor-mediated, and also was glucose-dependent.
      This study demonstrates that odor compounds can be recognized by gut-expressed
      ORs during meal ingestion and therefore, participate in the glucose homeostasis
      by inducing the secretion of gut-peptides.

PMID- 29070886
TI  - Poly (ionic liquid)-Based Breath Figure Films: A New Kind of Honeycomb Porous
      Films with Great Extendable Capability.
AB  - In this work, we reported a new method for the convenient fabrication of various
      functional porous films, which cannot be directly generated using breath figures
      (BFs). A series of polystyrene-b-poly (ionic liquid) (PS-b-PIL) block copolymers
      were employed for BFs process for the first time. It was found that PS-b-PIL
      could form well-defined BFs porous structure. Remarkably, the described PS-b-PIL
      copolymers are prone to form hierarchical structure, and the formed pore
      structure is strongly dependent on the used experimental parameters. Importantly,
      we found that the anion exchange could provide as an effective means, by which
      the porous films could be further and facilely converted into other functional
      films. As a demonstration, in our case, porous films with different surface
      (hydrophilic and hydrophobic) property, porous polydopamine films decorated with
      Au nanoparticles or glutathione and porous SiO2 films were prepared by using
      different counteranions as well as further conversion. Due to the unlimited
      combination of cation and anion in ionic liquid moiety, all the results indicate
      that the BFs films generated by using PS-PIL could serve as a platform to access
      various functional porous films by a simple counteranion exchange, showing a
      great extendable capability.

PMID- 29070887
TI  - New reverse genetics and transfection methods to rescue arboviruses in mosquito
      cells.
AB  - Reverse genetics is a critical tool to decrypt the biological properties of
      arboviruses. However, whilst reverse genetics methods have been usually applied
      to vertebrate cells, their use in insect cells remains uncommon due to the
      conjunction of laborious molecular biology techniques and of specific
      difficulties surrounding the transfection of such cells. To leverage reverse
      genetics studies in both vertebrate and mosquito cells, we designed an improved
      DNA transfection protocol for insect cells and then demonstrated that the simple
      and flexible ISA (Infectious Subgenomic Amplicons) reverse-genetics method can be
      efficiently applied to both mammalian and mosquito cells to generate in days
      recombinant infectious positive-stranded RNA viruses belonging to genera
      Flavivirus (Japanese encephalitis, Yellow fever, West Nile and Zika viruses) and
      Alphavirus (Chikungunya virus). This method represents an effective option to
      potentially overcome technological issues related to the study of arboviruses.

PMID- 29070888
TI  - Burial-induced oxygen-isotope re-equilibration of fossil foraminifera explains
      ocean paleotemperature paradoxes.
AB  - Oxygen-isotope compositions of fossilised planktonic and benthic foraminifera
      tests are used as proxies for surface- and deep-ocean paleotemperatures,
      providing a continuous benthic record for the past 115 Ma. However, visually
      imperceptible processes can alter these proxies during sediment burial. Here, we
      investigate the diffusion-controlled re-equilibration process with experiments
      exposing foraminifera tests to elevated pressures and temperatures in
      isotopically heavy artificial seawater (H218O), followed by scanning electron
      microscopy and quantitative NanoSIMS imaging: oxygen-isotope compositions changed
      heterogeneously at submicrometer length scales without any observable
      modifications of the test ultrastructures. In parallel, numerical modelling of
      diffusion during burial shows that oxygen-isotope re-equilibration of fossil
      foraminifera tests can cause significant overestimations of ocean
      paleotemperatures on a time scale of 107 years under natural conditions. Our
      results suggest that the late Cretaceous and Paleogene deep-ocean and high
      latitude surface-ocean temperatures were significantly lower than is generally
      accepted, thereby explaining the paradox of the low equator-to-pole surface-ocean
      thermal gradient inferred for these periods.

PMID- 29070889
TI  - Multi-heterodyne two dimensional coherent spectroscopy using frequency combs.
AB  - Optical multi-dimensional coherent spectroscopy is a powerful technique for
      studying the structure, properties and ultrafast dynamics of atoms, molecules,
      semiconductor materials and complex systems. Current implementations of multi
      dimensional coherent spectroscopy have long acquisition times and/or limited
      spectral resolution. In addition, most of the techniques utilize complex
      geometries or phase cycling schemes to isolate non-linear signals. We demonstrate
      a novel approach of using frequency combs to perform rapid, high resolution and
      background free multi-dimensional coherent spectroscopy of semiconductor
      materials. Our approach is inspired by dual-comb spectroscopy, which has been
      proven to be a versatile tool for obtaining one dimensional absorption spectra
      with high resolution in a short acquisition time. We demonstrate the method using
      a GaAs multi-quantum well sample.

PMID- 29070891
TI  - Damage mechanisms in defected natural fibers.
AB  - A novel experimental setup is presented to reveal damage mechanisms in bast
      fibers. 3D imaging at submicronic scale based on X-ray micro-tomography is
      combined with in-situ tensile experiments of both elementary fibers and bundles.
      The results reveal that the relevant scale that drives failure of hemp
      lignocellulosic fibers is submicronic. In-situ tensile experiments assisted by X
      ray micro-tomography shows complex damage mechanisms involving the constitutive
      sub-layer structure, fiber extraction defects like kink bands, and the tubular
      porosity of the natural fiber.

PMID- 29070890
TI  - Rapid and PCR-free DNA Detection by Nanoaggregation-Enhanced Chemiluminescence.
AB  - The aggregation of gold nanoparticles (AuNPs) is known to induce an enhancement
      of localized surface plasmon resonance due to the coupling of plasmonic fields of
      adjacent nanoparticles. Here we show that AuNPs aggregation also causes a
      significant enhancement of chemiluminescence in the presence of luminophores. The
      phenomenon is used to introduce a rapid and sensitive DNA detection method that
      does not require amplification. DNA probes conjugated to AuNPs were used to
      detect a DNA target sequence specific to the fungus Ceratocystis fagacearum,
      causal agent of oak wilt. The hybridization of the DNA target with the DNA probes
      results in instantaneous aggregation of AuNPs into nanoballs, leading to a
      significant enhancement of luminol chemiluminescence. The enhancement reveals a
      linear correlation (R2 = 0.98) to the target DNA concentration, with a limit of
      detection down to 260 fM (260 * 10-15 M), two orders of magnitude higher than the
      performance obtained with plasmonic colorimetry and absorption spectrometry of
      single gold nanoparticles. Furthermore, the detection can be performed within 22
      min using only a portable luminometer.

PMID- 29070893
TI  - Linking fishes to multiple metrics of coral reef structural complexity using
      three-dimensional technology.
AB  - Structural complexity strongly influences biodiversity and ecosystem
      productivity. On coral reefs, structural complexity is typically measured using a
      single and small-scale metric ('rugosity') that represents multiple spatial
      attributes differentially exploited by species, thus limiting a complete
      understanding of how fish associate with reef structure. We used a novel approach
      to compare relationships between fishes and previously unavailable components of
      reef complexity, and contrasted the results against the traditional rugosity
      index. This study focused on damselfish to explore relationships between fishes
      and reef structure. Three territorial species, with contrasting trophic habits
      and expected use of the reef structure, were examined to infer the potential
      species-specific mechanisms associated with how complexity influences habitat
      selection. Three-dimensional reef reconstructions from photogrammetry quantified
      the following metrics of habitat quality: 1) visual exposure to predators and
      competitors, 2) density of predation refuges and 3) substrate-related food
      availability. These metrics explained the species distribution better than the
      traditional measure of rugosity, and each species responded to different
      complexity components. Given that a critical effect of reef degradation is loss
      of structure, adopting three-dimensional technologies potentially offers a new
      tool to both understand species-habitat association and help forecast how fishes
      will be affected by the flattening of reefs.

PMID- 29070892
TI  - Mitochondrial-nuclear crosstalk, haplotype and copy number variation distinct in
      muscle fiber type, mitochondrial respiratory and metabolic enzyme activities.
AB  - Genes expressed in mitochondria work in concert with those expressed in the
      nucleus to mediate oxidative phosphorylation (OXPHOS), a process that is relevant
      for muscle metabolism and meat quality. Mitochondrial genome activity can be
      efficiently studied and compared in Duroc and Pietrain pigs, which harbor
      different mitochondrial haplotypes and distinct muscle fiber types, mitochondrial
      respiratory activities, and fat content. Pietrain pigs homozygous-positive for
      malignant hyperthermia susceptibility (PiPP) carried only haplotype 8 and showed
      the lowest absolute mtDNA copy number accompanied by a decrease transcript
      abundance of mitochondrial-encoded subunits ND1, ND6, and ATP6 and nuclear
      encoded subunits NDUFA11 and NDUFB8. In contrast, we found that haplotype 4 of
      Duroc pigs had significantly higher mitochondrial DNA (mtDNA) copy numbers and an
      increase transcript abundance of mitochondrial-encoded subunits ND1, ND6, and
      ATP6. These results suggest that the variation in mitochondrial and nuclear
      genetic background among these animals has an effect on mitochondrial content and
      OXPHOS system subunit expression. We observed the co-expression pattern of
      mitochondrial and nuclear encoded OXPHOS subunits suggesting that the
      mitochondrial-nuclear crosstalk functionally involves in muscle metabolism. The
      findings provide valuable information for understanding muscle biology processes
      and energy metabolism, and may direct use for breeding strategies to improve meat
      quality and animal health.

PMID- 29070894
TI  - Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma
      cells: an in vitro study.
AB  - Failure of treatment for cancer in clinic by radio/chemotherapy is generally
      attributed to tumour resistance. Therefore, it is important to develop strategies
      to increase the cytotoxicity of tumour cells by radiation in combination with
      unique tumour selective cytotoxic agents. We evaluated the potential of ellagic
      acid (EA) as an enhancer of oxidative stress in cancer cells. HepG2 cells were
      treated with EA (10 uM) for 12 h prior to exposure of single 7.5 Gy dose of
      irradiation. Treatment of HepG2 cells with EA and gamma radiation showed
      increased reactive oxygen species generation, up regulation of p53 protein
      expression, decreased survival markers level like p-Akt, p-NF-kB and p-STAT3
      which were significantly higher after radiation treatment alone. We also found
      that combination treatment increased G2/M phase cell population, decreased IL-6,
      COX-2 and TNF-alpha expression and caused a loss in mitochondrial membrane
      potential with decreased level of angiogenesis marker MMP-9. Over expression of
      Bax and activation of caspase 3 indicated the apoptosis of the cells. The results
      provided a strong unique strategy to kill cancer cells HepG2, using less
      radiation dose along with effective pro-oxidant dose of EA.

PMID- 29070895
TI  - Language lateralization during the Chinese semantic task relates to the
      contralateral cerebra-cerebellar interactions at rest.
AB  - Aiming to investigate whether handedness-related language lateralization is
      related to the intrinsic resting-state functional connectivity (RSFC) pattern
      within the language network, the present study integrated the information of
      functional activations during a semantic task of Chinese characters and FC in
      resting-state based on functional magnetic resonance imaging (fMRI) data of
      healthy left handers (LH) and right handers (RH). RSFC was calculated on a voxel
      based level between the seed regions chosen from functional activations during
      the task and the rest of the brain. The results demonstrated that LH had
      significantly stronger RSFC than RH between the cerebellum and supratentorial
      areas of the frontal, parietal and temporal lobe, and between the occipital lobe
      and frontal/parietal lobe. Correlation analysis showed that RSFC values between
      right MFG and left cerebellum_crus2, between SMA and right cerebellum_crus2, and
      between the right cerebellum_crus1 and left MFG were negatively correlated with
      cerebral laterality index in LH and RH groups. Our results highlight key nodes of
      Chinese language brain network processing in the cerebellum, and suggest that
      atypical language dominance relates to stronger crossed reciprocal RSFC in the
      frontal-cerebellar system. The findings provide new insights into the intrinsic
      FC substrates underlying the atypical language lateralization of LH.

PMID- 29070896
TI  - A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a
      pilot study focused on pancreatic and ovarian cancer.
AB  - Proteolytic enzymes have shown efficacy in cancer therapy. We present a
      combination of the two pro-enzymes Trypsinogen and Chymotrypsinogen A with potent
      in vitro and in vivo anti-tumour efficacy. A synergetic anti-tumour effect for
      Trypsinogen and Chymotrypsinogen A was determined at a ratio 1:6 (named PRP)
      using 24 human cancer cell lines. The antiangiogenic effect of PRP was analysed
      by matrigel-based tube formation and by fibrous capsule formation assays.
      Furthermore, cell invasion and wound healing assays together with qRT-PCR
      determination of epithelial-to-mesenchymal transition (EMT) markers were
      performed on human cancer cells treated with PRP. Additionally, in vivo
      pharmacokinetic studies were implemented and the PRP's anti-tumour efficacy was
      explored against orthotopic pancreatic and ovarian cancer tumours. PRP
      formulation was proven to inhibit in vitro angiogenesis, tumour growth, cancer
      cell migration and invasiveness; and to be an effective and well tolerated in
      vivo anti-tumour treatment. Finally, the clinical efficacy of a suppository
      formulation containing both pancreatic pro-enzymes in the context of a UK
      Pharmaceuticals Special Scheme was evaluated in advanced cancer patients.
      Consequently, PRP could have relevant oncological clinical applications for the
      treatment of advanced or metastatic pancreatic adenocarcinoma and advanced
      epithelial ovarian cancer.

PMID- 29070897
TI  - Newly learned categories induce pre-attentive categorical perception of faces.
AB  - Face perception is modulated by categorical information in faces, which is known
      as categorical perception (CP) of faces. However, it remains unknown whether CP
      of faces is humans' inborn capability or the result of acquired categories. Here,
      we examined whether and when newly learned categories affect face perception. A
      short-term training method was employed in which participants learned new
      categories of face stimuli. Behaviorally, using an AB-X discrimination task, we
      found that the discrimination accuracy of face pairs from different learned
      categories was significantly higher than that of faces from the same category.
      Neurally, using a visual oddball task, we found that deviant stimuli whose
      category differed from standard stimuli evoked a larger N170. Importantly, the
      visual mismatch negativity (vMMN), starting from 140 ms after stimuli onset, was
      stronger with the between-category deviants than with the within-category
      deviants under the unattended condition. Altogether, our study provides empirical
      evidence indicating that CP of faces could be induced by newly learned
      categories, and this effect occurs automatically during an early stage of
      processing.

PMID- 29070898
TI  - Synthesis of tunable porosity of fluorine-enriched porous organic polymer
      materials with excellent CO2, CH4 and iodine adsorption.
AB  - We herein report the construction of four the novel fluorine-enriched conjugated
      microporous polymers (FCMP-600@1-4), which have permanent porous structures and
      plenty of fluorine atoms in the skeletons as effective sorption sites. Among
      them, FCMP-600@4 shows considerable adsorption capacity of CO2 of 5.35 mmol g-1
      at 273 K, and 4.18 mmol g-1 at 298 K, which is higher than the reported values
      for most porous polymers. In addition, FCMP-600@1-4 display high selectivity of
      CO2/N2 and high CH4 uptakes.

PMID- 29070900
TI  - New Routes for Refinery of Biogenic Platform Chemicals Catalyzed by Cerium Oxide
      supported Ruthenium Nanoparticles in Water.
AB  - Highly selective hydrogenative carbon-carbon bond scission of biomass-derived
      platform oxygenates was achieved with a cerium oxide-supported ruthenium
      nanoparticle catalyst in water. The present catalyst enabled the selective
      cleavage of carbon-carbon sigma bonds adjacent to carboxyl, ester, and
      hydroxymethyl groups, opening new eight synthetic routes to valuable chemicals
      from biomass derivatives. The high selectivity for such carbon-carbon bond
      scission over carbon-oxygen bonds was attributed to the multiple catalytic roles
      of the Ru nanoparticles assisted by the in situ formed Ce(OH)3.

PMID- 29070899
TI  - Impaired BKCa channel function in native vascular smooth muscle from humans with
      type 2 diabetes.
AB  - Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants
      of vascular smooth muscle excitability. Impaired BKCa channel function through
      remodeling of BKCa beta1 expression and function contributes to vascular
      complications in animal models of diabetes. Yet, whether similar alterations
      occur in native vascular smooth muscle from humans with type 2 diabetes is
      unclear. In this study, we evaluated BKCa function in vascular smooth muscle from
      small resistance adipose arteries of non-diabetic and clinically diagnosed type 2
      diabetic patients. We found that BKCa channel activity opposes pressure-induced
      constriction in human small resistance adipose arteries, and this is compromised
      in arteries from diabetic patients. Consistent with impairment of BKCa channel
      function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+
      sparks were lower in cells from diabetic patients. BKCa channels in diabetic
      cells exhibited reduced Ca2+ sensitivity, single-channel open probability and
      tamoxifen sensitivity. These effects were associated with decreased functional
      coupling between BKCa alpha and beta1 subunits, but no change in total protein
      abundance. Overall, results suggest impairment in BKCa channel function in
      vascular smooth muscle from diabetic patients through unique mechanisms, which
      may contribute to vascular complications in humans with type 2 diabetes.

PMID- 29070901
TI  - The neural representation of human versus nonhuman bipeds and quadrupeds.
AB  - How do humans recognize humans among other creatures? Recent studies suggest that
      a preference for conspecifics may emerge already in perceptual processing, in
      regions such as the right posterior superior temporal sulcus (pSTS), implicated
      in visual perception of biological motion. In the current functional MRI study,
      participants viewed point-light displays of human and nonhuman creatures moving
      in their typical bipedal (man and chicken) or quadrupedal mode (crawling-baby and
      cat). Stronger activity for man and chicken versus baby and cat was found in the
      right pSTS responsive to biological motion. The novel effect of pedalism suggests
      that, if right pSTS contributes to recognizing of conspecifics, it does so by
      detecting perceptual features (e.g. bipedal motion) that reliably correlate with
      their appearance. A searchlight multivariate pattern analysis could decode humans
      and nonhumans across pedalism in the left pSTS and bilateral posterior cingulate
      cortex. This result implies a categorical human-nonhuman distinction, independent
      from within-category physical/perceptual variation. Thus, recognizing
      conspecifics involves visual classification based on perceptual features that
      most frequently co-occur with humans, such as bipedalism, and retrieval of
      information that determines category membership above and beyond visual
      appearance. The current findings show that these processes are at work in
      separate brain networks.

PMID- 29070902
TI  - Mycobacterium smegmatis PafBC is involved in regulation of DNA damage response.
AB  - Two genes, pafB and pafC, are organized in an operon with the Pup-ligase gene
      pafA, which is part of the Pup-proteasome system (PPS) present in mycobacteria
      and other actinobacteria. The PPS is crucial for Mycobacterium tuberculosis
      resistance towards reactive nitrogen intermediates (RNI). However, pafB and pafC
      apparently play only a minor role in RNI resistance. To characterize their
      function, we generated a pafBC deletion in Mycobacterium smegmatis (Msm).
      Proteome analysis of the mutant strain revealed decreased cellular levels of
      various proteins involved in DNA damage repair, including recombinase A (RecA).
      In agreement with this finding, Msm DeltapafBC displayed increased sensitivity to
      DNA damaging agents. In mycobacteria two pathways regulate DNA repair genes: the
      LexA/RecA-dependent SOS response and a predominant pathway that controls gene
      expression via a LexA/RecA-independent promoter, termed P1. PafB and PafC feature
      winged helix-turn-helix DNA binding motifs and we demonstrate that together they
      form a stable heterodimer in vitro, implying a function as a heterodimeric
      transcriptional regulator. Indeed, P1-driven transcription of recA was decreased
      in Msm DeltapafBC under standard conditions and induction of recA expression upon
      DNA damage was strongly impaired. Taken together, our data indicate an important
      regulatory function of PafBC in the mycobacterial DNA damage response.

PMID- 29070904
TI  - A new low-cost, compact, auto-phoropter for refractive assessment in developing
      countries.
AB  - Using a phoropter to measure the refractive error is one of the most commonly
      used methods by ophthalmologists and optometrists. Here, we demonstrate design
      and fabrication of a portable automatic phoropter with no need for patient's
      feedback. The system is based on three tunable-focus fluidic lenses and thin-film
      holographic optical elements to perform automatic refractive error measurement
      and provide a diagnostic prescription without supervision. Three separate lenses
      are deployed to correct the defocus and astigmatism. The refractive error is
      measured using a Shack-Hartmann wavefront sensor that calculates the Zernike
      values of an infrared wavefront emerging from the eye. Holographic optical
      elements steer the emerging wavefront into the wavefront sensor, while
      simultaneously providing an unobstructed view for the subject. The power of each
      lens is controlled by pumping a liquid in and out of the lens chamber using servo
      motor actuated diaphragm pumps. Spherical and cylindrical correction range of -10
      to +10 diopters with 0.1 diopter increments is achieved in less than 15 seconds
      using wavefront sensor feedback to the pumps. This system can be used in rapid
      screening of large patient populations especially in the developing countries
      that lack sufficient facilities and specialist doctors.

PMID- 29070903
TI  - Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced
      Non-Alcoholic Steatohepatitis by Regulating Autophagy.
AB  - Previous studies have demonstrated that saturated fatty acids (SFAs) are more
      lipotoxic than unsaturated fatty acids (UFAs) in inhibiting hepatic autophagy and
      promoting non-alcoholic steatohepatitis (NASH). However, there have been few
      studies have investigated the effects of carbon chain length on SFA-induced
      autophagy impairment and lipotoxicity. To investigate whether SFAs with shorter
      carbon chain lengths have differential effects on hepatic autophagy and NASH
      development, we partially replaced lard with coconut oil to elevate the ratio of
      medium-chain fatty acids (MCFAs) to long-chain fatty acids (LCFAs) in a mouse
      high-fat diet (HFD) and fed mice for 16 weeks. In addition, we treated HepG2
      cells with different combinations of fatty acids to study the mechanisms of MCFAs
      mediated hepatic protections. Our results showed that increasing dietary
      MCFA/LCFA ratio mitigated HFD-induced Type 2 diabetes and NASH in mice.
      Importantly, we demonstrated that increased MCFA ratio exerted its protective
      effects by restoring Rubicon-suppressed autophagy. Our study suggests that the
      relative amount of LCFAs and MCFAs in the diet, in addition to the amount of
      SFAs, can significantly contribute to autophagy impairment and hepatic
      lipotoxicity. Collectively, we propose that increasing dietary MCFAs could be an
      alternative therapeutic and prevention strategy for Type 2 diabetes and NASH.

PMID- 29070905
TI  - The morphology of antennal lobe projection neurons is controlled by a POU-domain
      transcription factor Bmacj6 in the silkmoth Bombyx mori.
AB  - How to wire a neural circuit is crucial for the functioning of the nervous
      system. Here, we describe the neuroanatomy of the olfactory neurons in the spli
      mutant strain of silkmoth (Bombyx mori) to investigate the function of a
      transcription factor involved in neuronal wiring in the central olfactory
      circuit. The genomic structure of the gene Bmacj6, which encodes a class IV POU
      domain transcription factor, is disrupted in the spli mutant. We report the
      neuroanatomical abnormality in the morphology of the antennal lobe projection
      neurons (PNs) that process the sex pheromone. In addition to the mis-targeting of
      dendrites and axons, we found axonal bifurcation within the PNs. These results
      indicate that the morphology of neurons in the pheromone processing pathway is
      modified by Bmacj6.

PMID- 29070906
TI  - Family, personal, and social factors associated with the non-use of contraceptive
      methods during the first sexual experience in adolescent women.
AB  - Unplanned pregnancy and sexually transmitted infections (STIs) in adolescents
      continue to be major health problems around the world. They are associated with
      sex that occurs without contraceptive protection. We determined the relationship
      of family, personal, and social factors with the non-use of any contraceptive
      method during the first sexual experience in 1409 adolescent women. The most
      significant risk factors were being less than 15 years of age and lacking
      knowledge and awareness about contraceptive methods. In the family environment,
      the risk factors were living in an incomplete family and the existence of a poor
      relationship among the father, the mother, and the adolescents. Socialization
      with friends who became sexually active at an early age was also associated with
      having sex for the first time without protection. This information should be used
      in sexual and reproductive education programmes to prevent unplanned pregnancy
      and STIs in adolescent women.

PMID- 29070907
TI  - Co-infection of Chlamydia psittaci with H9N2, ORT and Aspergillus fumigatus
      contributes to severe pneumonia and high mortality in SPF chickens.
AB  - Since 2007, most areas of China have seen outbreaks of poultry airsacculitis,
      which causes hugely economic losses to the poultry industry. However, there are
      no effective measures to combat the problem. In this study, 105 rations were
      collected to isolate Aspergillus spp. from the diseased farms. In subsequent
      experiments, SPF chickens were inoculated with Ornithobacterium rhinotracheale
      (ORT), Chlamydia psittaci (C. psittaci) and Aspergillus fumigatus (A. fumigatus),
      and mortality rate, body weight gain and lesion score were evaluated. Of these
      ration samples, 63 (60.0%) were A. fumigates, 21 (20.0%) were Aspergillus niger
      (A. niger) and 11 (10.5%) were Aspergillus candidus (A. candidus). Furthermore,
      SPF birds infected with C. psittaci, ORT, H9N2 virus and A. fumigatus conidia
      exhibited a mortality rate of 40%, while simultaneous co-infection with C.
      psittaci, ORT and A. fumigatus resulted in a mortality rate of 20%. The avian
      airsacculitis was manifested in the C. psittaci + ORT/A. fumigatus, C. psittaci +
      H9N2 + ORT/A. fumigatus and C. psittaci + H9N2/A. fumigatus groups while others
      had transient respiratory diseases without mortality. Our survey indicates that
      feed-borne A. fumigatus is prevalent in poultry rations. The combination of C.
      psittaci, ORT, H9N2 and A. fumigatus conidia contributes to the replication of
      avian airsacculitis by aggravating the severe damage to the air sacs and lungs of
      chickens.

PMID- 29070908
TI  - Realization of Rectangular Artificial Spin Ice and Direct Observation of High
      Energy Topology.
AB  - In this work, we have constructed and experimentally investigated frustrated
      arrays of dipoles forming two-dimensional artificial spin ices with different
      lattice parameters (rectangular arrays with horizontal and vertical lattice
      spacings denoted by a and b respectively). Arrays with three different aspect
      ratios gamma = a/b = [Formula: see text], [Formula: see text] and [Formula: see
      text] are studied. Theoretical calculations of low-energy demagnetized
      configurations for these same parameters are also presented. Experimental data
      for demagnetized samples confirm most of the theoretical results. However, the
      highest energy topology (doubly-charged monopoles) does not emerge in our
      theoretical model, while they are seen in experiments for large enough gamma. Our
      results also insinuate that the string tension connecting two magnetic monopoles
      in a pair vanishes in rectangular lattices with a critical ratio gamma = gamma c 
      = [Formula: see text], supporting previous theoretical predictions.

PMID- 29070910
TI  - Molecular phylogeny and divergence times of Astragalus section Hymenostegis: An
      analysis of a rapidly diversifying species group in Fabaceae.
AB  - The taxa of Astragalus section Hymenostegis are an important element of
      mountainous and steppe habitats in Southwest Asia. A phylogenetic hypothesis of
      sect. Hymenostegis has been obtained from nuclear ribosomal DNA internal
      transcribed spacer (ITS) and plastid ycf1 sequences of up to 303 individuals from
      106 species, including all 89 taxa currently assigned to sect. Hymenostegis, 14
      species of other Astragalus sections, and two species of Oxytropis and one
      Biserrula designated as outgroups. Bayesian phylogenetic inference and parsimony
      analyses reveal that three species from two other closely related sections group
      within sect. Hymenostegis, making the section paraphyletic. DNA sequence
      diversity is generally very low among Hymenostegis taxa, which is consistent with
      recent diversification of the section. We estimate that diversification in sect.
      Hymenostegis occurred in the middle to late Pleistocene, with many species
      arising only during the last one million years, when environmental conditions in
      the mountain regions of Southwest and Central Asia cycled repeatedly between dry
      and more humid conditions.

PMID- 29070911
TI  - A simple surface plasmon resonance biosensor for detection of PML/RARalpha based
      on heterogeneous fusion gene-triggered nonlinear hybridization chain reaction.
AB  - In this work, a simple and enzyme-free surface plasmon resonance (SPR) biosensing
      strategy has been developed for highly sensitive detection of two major
      PML/RARalpha (promyelocytic leukemia, retinoic acid receptor alpha) subtypes
      based on the heterogeneous fusion gene-triggered nonlinear hybridization chain
      reaction (HCR). On the gold chip surface, the cascade self-assembly process is
      triggered after the introduction of PML/RARalpha. The different fragments of
      PML/RARalpha can specifically hybridize with capture probes (Cp) immobilized on
      the chip and the hybridization DNA1 (H1). Then, the nonlinear HCR is initiated by
      the complex of Cp-PML/RARalpha-H1 with the introduction of two hybridization DNA
      chains (H2 and H3). As a result, a dendritic nanostructure is achieved on the
      surface of chip, leading to a significant SPR amplification signal owing to its
      high molecular weight. The developed method shows good specificity and high
      sensitivity with detection limit of 0.72 pM for "L" subtype and 0.65 pM for "S"
      subtype. Moreover, this method has been successfully applied for efficient
      identification of clinical positive and negative PCR samples of the PML/RARalpha
      subtype. Thus, this developed biosensing strategy presents a potential platform
      for analysis of fusion gene and early diagnosis of clinical disease.

PMID- 29070912
TI  - Bi-directional regulation of acupuncture on extrahepatic biliary system: An
      approach in guinea pigs.
AB  - Clinically, acupuncture affects the motility of the extrahepatic biliary tract,
      but the underlining mechanisms are still unknown. We applied manual acupuncture
      (MA) and electrical acupuncture (EA) separately at acupoints Tianshu (ST25),
      Qimen (LR14), Yanglingquan (GB34), and Yidan (CO11) in forty guinea pigs (4
      groups) with or without atropinization under anesthesia while Sphincter of Oddi
      (SO) myoelectric activities and gallbladder pressure were monitored. In both MA
      and EA groups, stimulation at ST25 or LR14 significantly increased the frequency
      and amplitude of SO myoelectrical activities and simultaneously decreased the
      gallbladder pressure as compared to the pre-MA and pre-EA (P < 0.05). On the
      contrary, stimulation at GB34 or CO11 significantly decreased SO myoelectricity
      and increased the gallbladder pressure (P < 0.05). Pretreatment with atropine
      could abolish the effect of stimulation at acupoints ST25, GB34 and LR14 (P >
      0.05), although significant myoelectricity increases were still inducible with MA
      or EA stimulation at CO11 (P < 0.05). In summary, acupuncture has bi-directional
      effects to gallbladder pressure and SO function, which probably due to autonomic
      reflex and somatovisceral interactions.

PMID- 29070914
TI  - How paradata can illuminate technical, social and professional role changes
      between the Poverty in the UK (1967/1968) and Poverty and Social Exclusion in the
      UK (2012) surveys.
AB  - This article brings together analyses of the micro paradata 'by-products' from
      the 1967/1968 Poverty in the United Kingdom (PinUK) and 2012 Poverty and Social
      Exclusion in the UK (PSE) surveys to explore changes in the conditions of
      production over this 45 year period. We highlight technical, social and
      professional role continuities and changes, shaped by the institutionalisation of
      survey researchers, the professionalization of the field interviewer, and
      economisation. While there are similarities between the surveys in that field
      interviewers were and are at the bottom of the research hierarchy, we demonstrate
      an increasing segregation between the core research team and field interviewers.
      In PinUK the field interviewers are visible in the paper survey booklets; through
      their handwritten notes on codes and in written marginalia they can 'talk' to the
      central research team. In PSE they are absent from the computer mediated data,
      and from communication with the central team. We argue that, while there have
      been other benefits to field interviewers, their relational labour has become
      less visible in a shift from the exercise of observational judgement to an
      emphasis on standardisation. Yet, analyses of what field interviewers actually do
      show that they still need to deploy the same interpersonal skills and
      resourcefulness to secure and maintain interviews as they did 45 years
      previously.

PMID- 29070913
TI  - Advantages of later motherhood.
AB  - BACKGROUND: In high-income countries childbearing has been increasingly postponed
      since the 1970s and it is crucial to understand the consequences of this
      demographic shift. The literature has tended to characterize later motherhood as
      a significant health threat for children and parents. OBJECTIVES: We contribute
      to this debate by reviewing recent evidence suggesting that an older maternal age
      can also have positive effects. MATERIALS: Literature linking the age at
      parenthood with the sociodemographic characteristics of the parents, with
      macrolevel interactions, and with subjective well-being. METHODS: Comprehensive
      review of the existing literature. RESULTS: Recent studies show that there can
      also be advantages associated with later motherhood. First, whilst in past older
      mothers had low levels of education and large families, currently older mothers
      tend to have higher education and smaller families than their younger peers.
      Consequently, children born to older mothers in the past tended to have worse
      outcomes than children born to younger mothers, whilst the opposite is true in
      recent cohorts. Second, postponement of childbearing means that the child is born
      at a later date and in a later birth cohort, and may benefit from secular changes
      in the macroenvironment. Evidence shows that when the positive trends in the
      macroenvironment are strong they overweigh the negative effects of reproductive
      ageing. Third, existing studies show that happiness increases around and after
      childbirth among older mothers, whereas for younger mothers the effect does not
      exist or is short-lived. CONCLUSION: There are important sociodemographic
      pathways associated with postponement of childbearing which might compensate or
      even more than compensate for the biological disadvantages associated with
      reproductive ageing.

PMID- 29070909
TI  - A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly
      associated as predictors of beta-amyloid load in an AD cohort.
AB  - Alzheimer's Disease (AD) is the most common form of dementia, characterised by
      extracellular amyloid deposition as plaques and intracellular neurofibrillary
      tangles of tau protein. As no current clinical test can diagnose individuals at
      risk of developing AD, the aim of this project is to evaluate a blood-based
      biomarker panel to identify individuals who carry this risk. We analysed the
      levels of 22 biomarkers in clinically classified healthy controls (HC), mild
      cognitive impairment (MCI) and Alzheimer's participants from the well
      characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging.
      High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid
      deposition in HC, suggesting that these two biomarkers might be used to detect at
      risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY)
      exhibited altered levels in AD participants possessing the APOE epsilon4 allele.
      This suggests that the physiology of some potential biomarkers may be altered in
      AD due to the APOE epsilon4 allele, a major risk factor for AD. Taken together,
      these data highlight several potential biomarkers that can be used in a blood
      based panel to allow earlier identification of individuals at risk of developing
      AD and/or early stage AD for which current therapies may be more beneficial.

PMID- 29070915
TI  - Sentiment analysis of political communication: combining a dictionary approach
      with crowdcoding.
AB  - Sentiment is important in studies of news values, public opinion, negative
      campaigning or political polarization and an explosive expansion of digital
      textual data and fast progress in automated text analysis provide vast
      opportunities for innovative social science research. Unfortunately, tools
      currently available for automated sentiment analysis are mostly restricted to
      English texts and require considerable contextual adaption to produce valid
      results. We present a procedure for collecting fine-grained sentiment scores
      through crowdcoding to build a negative sentiment dictionary in a language and
      for a domain of choice. The dictionary enables the analysis of large text corpora
      that resource-intensive hand-coding struggles to cope with. We calculate the
      tonality of sentences from dictionary words and we validate these estimates with
      results from manual coding. The results show that the crowdbased dictionary
      provides efficient and valid measurement of sentiment. Empirical examples
      illustrate its use by analyzing the tonality of party statements and media
      reports.

PMID- 29070916
TI  - Clusters of cultures: diversity in meaning of family value and gender role items
      across Europe.
AB  - Survey data are often used to map cultural diversity by aggregating scores of
      attitude and value items across countries. However, this procedure only makes
      sense if the same concept is measured in all countries. In this study we argue
      that when (co)variances among sets of items are similar across countries, these
      countries share a common way of assigning meaning to the items. Clusters of
      cultures can then be observed by doing a cluster analysis on the (co)variance
      matrices of sets of related items. This study focuses on family values and gender
      role attitudes. We find four clusters of cultures that assign a distinct meaning
      to these items, especially in the case of gender roles. Some of these differences
      reflect response style behavior in the form of acquiescence. Adjusting for this
      style effect impacts on country comparisons hence demonstrating the usefulness of
      investigating the patterns of meaning given to sets of items prior to aggregating
      scores into cultural characteristics.

PMID- 29070917
TI  - A two-step approach for the analysis of hybrids in comparative social policy
      analysis: a nuanced typology of childcare between policies and regimes.
AB  - Typologies have represented an important tool for the development of comparative
      social policy research and continue to be widely used in spite of growing
      criticism of their ability to capture the complexity of welfare states and their
      internal heterogeneity. In particular, debates have focused on the presence of
      hybrid cases and the existence of distinct cross-national pattern of variation
      across areas of social policy. There is growing awareness around these issues,
      but empirical research often still relies on methodologies aimed at classifying
      countries in a limited number of unambiguous types. This article proposes a two
      step approach based on fuzzy-set ideal type analysis for the systematic analysis
      of hybrids at the level of both policies (step 1) and policy configurations or
      combinations of policies (step 2). This approach is demonstrated by using the
      case of childcare policies in European economies. In the first step, parental
      leave policies are analysed using three methods-direct, indirect, and combinatory
      to identify and describe specific hybrid forms at the level of policy analysis.
      In the second step, the analysis moves on to investigate the relationship between
      parental leave and childcare services. Clearly shows that many countries display
      characteristics normally associated with different types (hybrids and sub-types)
      . Therefore, this two-step approach demonstrates that disaggregated and
      aggregated analyses are equally important to account for hybrid welfare forms and
      make sense of the tensions and incongruences within and between policies.

PMID- 29070918
TI  - Spectral stability of periodic waves in the generalized reduced Ostrovsky
      equation.
AB  - We consider stability of periodic travelling waves in the generalized reduced
      Ostrovsky equation with respect to co-periodic perturbations. Compared to the
      recent literature, we give a simple argument that proves spectral stability of
      all smooth periodic travelling waves independent of the nonlinearity power. The
      argument is based on the energy convexity and does not use coordinate
      transformations of the reduced Ostrovsky equations to the semi-linear equations
      of the Klein-Gordon type.

PMID- 29070919
TI  - Optimal Product Placement.
AB  - We model a market, such as an online software market, in which an intermediary
      connects sellers and buyers by displaying sellers' products. With two vertically
      differentiated products, an intermediary can place either: (1) one product, not
      necessarily the better one, on the first page, and the other hidden on the second
      page; or (2) both products on the first page. We show that it can be optimal for
      the intermediary to obfuscate a product-possibly the better one-since this
      weakens price competition and allows the sellers to extract a greater surplus
      from buyers; however, it is not socially optimal. The choice of which one to
      obfuscate depends on the distribution of search costs.

PMID- 29070922
TI  - Ready to screen? Start with the goal in mind.

PMID- 29070920
TI  - The intrinsic value of choice: The propensity to under-delegate in the face of
      potential gains and losses.
AB  - Human beings are often faced with a pervasive problem: whether to make their own
      decision or to delegate the decision task to someone else. Here, we test whether
      people are inclined to forgo monetary rewards in order to retain agency when
      faced with choices that could lead to losses and gains. In a simple choice task,
      we show that participants choose to pay in order to control their own payoff more
      than they should if they were to maximize monetary rewards and minimize monetary
      losses. This tendency cannot be explained by participants' overconfidence in
      their own ability, as their perceived ability was elicited and accounted for. Nor
      can the results be explained by lack of information. Rather, the results seem to
      reflect an intrinsic value for choice, which emerges in the domain of both gains
      and of losses. Moreover, our data indicate that participants are aware that they
      are making suboptimal choices in the normative sense, but do so anyway,
      presumably for psychological gains.

PMID- 29070921
TI  - What is comprehensive school eye health?

PMID- 29070923
TI  - Developing better strategies for school eye health screening in India.

PMID- 29070924
TI  - Improving spectacle wear in school children.

PMID- 29070925
TI  - Use of ready-made spectacles in school eye health programmes.

PMID- 29070926
TI  - Helpful developments and technologies for school eye health programmes.

PMID- 29070927
TI  - Children's myopia: prevention and the role of school programmes.

PMID- 29070929
TI  - Understanding and looking after a retinoscope and trial lens set.

PMID- 29070928
TI  - How schools can help to build healthy, productive lives, free of trachoma.

PMID- 29070930
TI  - Lessons from the USAID Child Blindness Programme.

PMID- 29070931
TI  - Effect of Calotropis procera (madar) and amprolium supplementation on
      parasitological parameters of broilers during mixed Eimeria species infection.
AB  - AIM: An experiment was conducted on day old 168 broiler chicks to study the
      effect of 0.4% as well as 0.2% Calotropis procera (madar) leaf powder and 0.0125%
      amprolium supplementation on parasitological parameters of broilers during mixed
      Eimeria species infection. MATERIALS AND METHODS: Chicks were randomly divided
      into seven groups (I-VII) each with two replicates of 12 chicks. On 15th day of
      experiment, broilers of Group II, IV, VI, and VII were infected with 50,000
      sporulated oocysts of mixed Eimeria species. To evaluate the anticoccidial effect
      of different feed supplements percent fecal score, percent survival, percent
      weight gain, performance index (PI), average oocyst production, and percent
      reduction in oocyst production were calculated. RESULTS: It was observed that
      amprolium supplementation had maximum anticoccidial effect as it gave the best
      efficacy in terms of all parameters, whereas supplementation of 0.4% madar leaf
      powder showed nonsignificant difference with amprolium for some parameters such
      as percent survival, percent weight gain, and PI. CONCLUSION: It can be concluded
      that madar (C. procera) leaf powder and amprolium had comparable activity against
      coccidiosis. Hence, madar leaf powder may be used for the prevention and control
      of mixed Eimeria spp. infection prevalent in field conditions.

PMID- 29070932
TI  - Convergence and stability of the exponential Euler method for semi-linear
      stochastic delay differential equations.
AB  - The main purpose of this paper is to investigate the strong convergence and
      exponential stability in mean square of the exponential Euler method to semi
      linear stochastic delay differential equations (SLSDDEs). It is proved that the
      exponential Euler approximation solution converges to the analytic solution with
      the strong order [Formula: see text] to SLSDDEs. On the one hand, the classical
      stability theorem to SLSDDEs is given by the Lyapunov functions. However, in this
      paper we study the exponential stability in mean square of the exact solution to
      SLSDDEs by using the definition of logarithmic norm. On the other hand, the
      implicit Euler scheme to SLSDDEs is known to be exponentially stable in mean
      square for any step size. However, in this article we propose an explicit method
      to show that the exponential Euler method to SLSDDEs is proved to share the same
      stability for any step size by the property of logarithmic norm.

PMID- 29070933
TI  - A sharp Trudinger type inequality for harmonic functions and its applications.
AB  - The present paper introduces a sharp Trudinger type inequality for harmonic
      functions based on the Cauchy-Riesz kernel function, which includes modified
      Poisson type kernel in a half plane considered by Xu et al. (Bound. Value Probl.
      2013:262, 2013). As applications, we not only obtain Morrey representations of
      continuous linear maps for harmonic functions in the set of all closed bounded
      convex nonempty subsets of any Banach space, but also deduce the representation
      for set-valued maps and for scalar-valued maps of Dunford-Schwartz.

PMID- 29070934
TI  - Optimal bounds for Neuman-Sandor mean in terms of the convex combination of the
      logarithmic and the second Seiffert means.
AB  - In the article, we prove that the double inequality [Formula: see text] holds for
      [Formula: see text] with [Formula: see text] if and only if [Formula: see text]
      and [Formula: see text], where [Formula: see text], [Formula: see text] and
      [Formula: see text] denote the Neuman-Sandor, logarithmic and second Seiffert
      means of two positive numbers a and b, respectively.

PMID- 29070935
TI  - Existence of mild solutions for fractional nonautonomous evolution equations of
      Sobolev type with delay.
AB  - In this paper, we deal with a class of nonlinear fractional nonautonomous
      evolution equations with delay by using Hilfer fractional derivative, which
      generalizes the famous Riemann-Liouville fractional derivative. The definition of
      mild solutions for the studied problem was given based on an operator family
      generated by the operator pair [Formula: see text] and probability density
      function. Combining the techniques of fractional calculus, measure of
      noncompactness, and fixed point theorem with respect to k-set-contractive, we
      obtain a new existence result of mild solutions. The results obtained improve and
      extend some related conclusions on this topic. At last, we present an application
      that illustrates the abstract results.

PMID- 29070936
TI  - Robust solutions to box-constrained stochastic linear variational inequality
      problem.
AB  - We present a new method for solving the box-constrained stochastic linear
      variational inequality problem with three special types of uncertainty sets. Most
      previous methods, such as the expected value and expected residual minimization,
      need the probability distribution information of the stochastic variables. In
      contrast, we give the robust reformulation and reformulate the problem as a
      quadratically constrained quadratic program or convex program with a conic
      quadratic inequality quadratic program, which is tractable in optimization
      theory.

PMID- 29070937
TI  - On generalization of refinement of Jensen's inequality using Fink's identity and
      Abel-Gontscharoff Green function.
AB  - In this paper, we formulate new Abel-Gontscharoff type identities involving new
      Green functions for the 'two-point right focal' problem. We use Fink's identity
      and a new Abel-Gontscharoff-type Green's function for a 'two-point right focal'
      to generalize the refinement of Jensen's inequality given in (Horvath and Pecaric
      in Math. Inequal. Appl. 14: 777-791, 2011) from convex function to higher order
      convex function. Also we formulate the monotonicity of the linear functional
      obtained from these identities using the recent theory of inequalities for n
      convex function at a point. Further we give the bounds for the identities related
      to the generalization of the refinement of Jensen's inequality using inequalities
      for the Cebysev functional. Some results relating to the Gruss and Ostrowski-type
      inequalities are constructed.

PMID- 29070938
TI  - Advanced Nanoindentation Testing for Studying Strain-Rate Sensitivity and
      Activation Volume.
AB  - Nanoindentation became a versatile tool for testing local mechanical properties
      beyond hardness and modulus. By adapting standard nanoindentation test methods,
      simple protocols capable of probing thermally activated deformation processes can
      be accomplished. Abrupt strain-rate changes within one indentation allow
      determining the strain-rate dependency of hardness at various indentation depths.
      For probing lower strain-rates and excluding thermal drift influences, long-term
      creep experiments can be performed by using the dynamic contact stiffness for
      determining the true contact area. From both procedures hardness and strain-rate,
      and consequently strain-rate sensitivity and activation volume can be reliably
      deducted within one indentation, permitting information on the locally acting
      thermally activated deformation mechanism. This review will first discuss various
      testing protocols including possible challenges and improvements. Second, it will
      focus on different examples showing the direct influence of crystal structure
      and/or microstructure on the underlying deformation behavior in pure and highly
      alloyed material systems.

PMID- 29070939
TI  - Epiretinal membrane in a subject after transvitreal delivery of palucorcel (CNTO
      2476).
AB  - BACKGROUND: A 70-year-old woman with retinitis pigmentosa experienced an
      epiretinal membrane (ERM) formation and a tractional retinal detachment (RD)
      following subretinal administration of palucorcel (CNTO 2476), a novel human
      umbilical tissue-derived cell-based therapy, as part of a Phase I study. The
      clinical course and results of a histologic examination of the ERM, which was
      peeled during surgery to repair the RD, are described here. METHODS: In this open
      label, first-in-human, Phase I study (NCT00458575), two of seven subjects
      developed RD, with an ERM formation reported in a woman receiving a targeted dose
      of 3.0*105 palucorcel administered via a transvitreal route. A sample of the ERM
      was retained for analysis following the ERM peeling procedure. Clinical outcomes
      and ERM histology, based on immunocytochemistry analyses and fluorescence in situ
      hybridization (FISH) staining, were evaluated. RESULTS: We first noted the RD and
      formation of the ERM at 26 days after palucorcel administration. The ERM was
      cellular and contained multiple cell types, including Muller glial cells, immune
      cells, neurites, retinal pigment epithelial cells, and palucorcel. The majority
      of cells were not actively dividing. FISH staining showed a subset of Y
      chromosome-positive cells in the ERM from this woman, supporting the presence of
      palucorcel (derived from umbilical cord tissue of male neonate). Palucorcel did
      not differentiate into Muller glia, immune cells, neurites, or retinal pigment
      epithelial cells. DISCUSSION: The development of an ERM containing both subject
      (self) cells and palucorcel suggests that palucorcel egress in the vitreal cavity
      after retinotomy may contribute to ERM formation and RD and that an alternative
      delivery method will be required before further studies are conducted. Subsequent
      clinical research using alternative subretinal delivery methods for palucorcel in
      other indications suggests that membrane development does not occur when
      palucorcel is delivered without retinal perforation.

PMID- 29070940
TI  - Education and patient preferences for treating type 2 diabetes: a stratified
      discrete-choice experiment.
AB  - PURPOSE: Diabetes is a chronic condition that is more prevalent among people with
      lower educational attainment. This study assessed the treatment preferences of
      patients with type 2 diabetes by educational attainment. METHODS: Patients with
      type 2 diabetes were recruited from a national online panel in the US. Treatment
      preferences were assessed using a discrete-choice experiment. Participants
      completed 16 choice tasks in which they compared pairs of treatment profiles
      composed of six attributes: A1c decrease, stable blood glucose, low blood
      glucose, nausea, treatment burden, and out-of-pocket cost. Choice models and
      willingness-to-pay (WTP) estimates were estimated using a conditional logit model
      and were stratified by educational status. RESULTS: A total of 231 participants
      with a high school diploma or less education, 156 participants with some college
      education, and 165 participants with a college degree or more completed the
      survey. Participants with a college degree or more education were willing to pay
      more for A1c decreases ($58.84, standard error [SE]: 10.6) than participants who
      had completed some college ($28.47, SE: 5.53) or high school or less ($17.56, SE:
      3.55) (p<=0.01). People with a college education were willing to pay more than
      people with high school or less to avoid nausea, low blood glucose events during
      the day/night, or two pills per day. CONCLUSION: WTP for aspects of diabetes
      medication differed for people with a college education or more and a high school
      education or less. Advanced statistical methods might overcome limitations of
      stratification and advance understanding of preference heterogeneity for use in
      patient-centered benefit-risk assessments and personalized care approaches.

PMID- 29070941
TI  - Medication nonadherence among South American patients with schizophrenia.
AB  - OBJECTIVE: The objective of this research was to quantify nonadherence to
      medication and explore the determinants of nonadherence in patients diagnosed
      with schizophrenia (SZ) from three countries in Latin America (Bolivia, Peru, and
      Chile). METHODS: This study was conducted in public mental health centers in
      Bolivia, Peru, and Chile. The data collected included drug attitude inventory
      (DAI-10), sociodemographic information, and clinical and treatment
      characteristics of patients with SZ. Multivariate analysis with multiple linear
      regression was then performed to identify variables that were potentially
      associated with the DAI score (dependent variable). RESULTS: Two hundred and
      fifty-three patients diagnosed with SZ participated in the study and 247 fully
      completed the DAI-10. In the multivariate analysis, medication nonadherence was
      associated with being a woman (beta=-0.16, p=0.029), younger age (beta=0.17,
      p=0.020), younger age at onset of disease (beta=-0.17, p=0.019), and lower
      insight (beta=-0.30, p<0.001). CONCLUSION: Being a female, younger age, younger
      age at onset of disease, and lower insight were the main features associated with
      nonadherence. If future longitudinal studies confirm these findings, these
      factors should not be neglected in Latin American mental health public policies
      to address the problem of nonadherence.

PMID- 29070942
TI  - Odor selectivity of hyposmia and cognitive impairment in patients with
      Parkinson's disease.
AB  - OBJECTIVE: Hyposmia is one of the earliest non-motor features of Parkinson's
      disease (PD) and can precede the onset of motor symptoms by years. Most of the
      current olfactory detection tests are targeted at Western populations. The exact
      relationship between hyposmia and cognitive impairment is unknown. The purpose of
      the study was to find bromines that can effectively identify olfactory
      dysfunction and investigate the relationship between hyposmia and cognitive
      function in early, non-demented, drug-naive patients with PD in the People's
      Republic of China. METHODS: Sixty-three early, non-demented, drug-naive patients
      with PD and 55 healthy controls were enrolled in the study. The T&T olfactometer
      and a Chinese version of Montreal Cognitive Assessment (MoCA) were applied to
      assess subjects' olfactory and cognitive functions. Patients with PD also
      completed the Modified Unified Parkinson's disease-rating scale (UPDRS) and Hoehn
      and Yahr (H&Y) scale. RESULTS: Patients with PD had lower scores of visuospatial
      and executive function (p=0.000), attention (p=0.03), and delayed recall
      (p=0.001) than controls. beta-phenylethyl alcohol (floral smell, smell of rose
      petals) and isovaleric acid (smell of sweat, stuffy socks) were more sensitive
      for identifying hyposmia in patients with PD than three other odors. Multivariate
      logistic regression analysis showed that impaired visuospatial and executive
      function was associated with hyposmia (p=0.013), but was independent of other PD
      associated variables. CONCLUSION: Hyposmia was common in early, non-demented,
      drug-naive PD patients. beta-Phenylethyl alcohol and isovaleric acid were more
      superior for identifying hyposmia in early non-demented Chinese patients with PD.
      Hyposmia was associated with impaired visuospatial and executive function in
      patients with PD. Further prospective studies that apply a series of
      neuropsychological tests and functional magnetic resonance imaging methods in
      large samples in multicenter studies are needed to confirm our findings and to
      investigate the relationship between hyposmia and cognitive function with disease
      progression in patients with PD.

PMID- 29070943
TI  - The incidence of depression among residents of assisted living: prevalence and
      related risk factors.
AB  - AIM: This study aims to recognize and estimate the prevalence of depression and
      its risk factors among residents of assisted living facilities (ALs) in Jordan.
      BACKGROUND: Depression is commonly experienced by residents of ALs. The condition
      is, however, often misunderstood as a part of normal aging and may be overlooked
      by health care professionals. Little is known about the extent of depression and
      its risk factors among AL residents in Jordan. SUBJECTS AND METHODS: A national
      representative sample of 221 residents selected from all AL units across Jordan
      was recruited to the study. Data on expected risk factors for depression were
      collected, including sociodemographics; smoking status; number of roommates;
      number of family members; assessments for cognitive functioning, for lower limb
      functioning, for hand, shoulder, and arm impairments; and oral health status.
      Levels of depression among the sample respondents were also assessed. RESULTS:
      The study found that around 60% of the participants reported depressive
      manifestations, with 48.0% of AL residents exhibiting impaired cognitive
      functions, one-third (33.2%) having >50% upper limb disability, two-thirds
      (63.2%) being at moderate risk of falls, and 69.7% having fair to poor oral
      health status. Being female, and having a higher level of education, disability
      of the upper limbs, and impairment of cognitive functions were found to be
      independent risk factors for depression in participants. CONCLUSION: Depression
      is relatively common among residents of AL units in Jordan. Health care
      professionals, nurses, physiotherapists, and dentists working in these facilities
      need to work cooperatively to identify the manifestations of depression in
      residents and collaboratively implement the best practice in the treatment of
      depression and circumvent its long-term impacts on the health of residents.

PMID- 29070944
TI  - Evaluation of various equations for estimating renal function in elderly Chinese
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The clinical assessment of kidney function based on the estimated
      glomerular filtration rate (GFR) in older patients remains controversial. This
      study evaluated the concordance and feasibility of using various creatinine-based
      equations for estimating GFR in elderly Chinese patients with type 2 diabetes
      mellitus (T2DM). METHODS: A cross-sectional analytical study was conducted in
      21,723 older diabetic patients (>=60 years) based on electronic health records
      (EHR) for Minhang District, Shanghai, China. The concordance of chronic kidney
      disease (CKD) classification among different creatinine-based equations was
      assessed based on Kappa values, intraclass correlation coefficient (ICC)
      statistics, and the eGFR agreement between the equations was tested using Bland
      Altman plots. The GFR was estimated using the Cockcroft-Gault (CG), Berlin
      Initiative Study 1 (BIS1), simplified Modification of Diet in Renal Disease
      (MDRD), MDRD modified for Chinese populations (mMDRD), chronic kidney disease
      epidemiology collaboration (CKD-EPI), CKD-EPI in Asians (CKD-EPI-Asia), and
      Ruijin equations. RESULTS: Overall, the proportion of CKD stages 3-5 (eGFR <60
      mL/min/1.73 m2) was calculated as 28.9%, 39.1%, 11.8%, 8.4%, 14.3%, 11.5%, and
      12.7% by the eGFRCG, eGFRBIS1, eGFRMDRD, eGFRmMDRD, eGFRCKD-EPI, eGFRCKD-EPI
      Asia, and eGFRRuijin equations, respectively. The concordance of albuminuria and
      decreased eGFR based on the different equations was poor by both the Kappa (<0.2)
      and ICC (<0.4) statistics. The CKD-EPI-Asia equation resulted in excellent
      concordance with the CKD-EPI (ICC =0.931), MDRD (ICC =0.963), mMDRD (ICC =0.892),
      and Ruijin (ICC =0.956) equations for the classification of CKD stages, whereas
      the BIS1 equation exhibited good concordance with the CG equation (ICC =0.809).
      In addition, significant differences were observed for CKD stage 1 among all
      these equations. CONCLUSION: Accurate GFR values are difficult to estimate using
      creatinine-based equations in older diabetic patients. Kidney function is
      complex, and the staff need to be aware of the individualized consideration of
      other risk factors or markers of reduced renal function in clinical practice.

PMID- 29070945
TI  - Minimal important difference and responsiveness of 2-minute walk test performance
      in people with COPD undergoing pulmonary rehabilitation.
AB  - BACKGROUND AND OBJECTIVES: Field exercise tests (eg, 6-minute walk test [6MWT])
      are important measures of functional exercise capacity in people with COPD.
      Shorter tests such as the 2-minute walk test (2MWT) may offer advantages in some
      populations but lack information about responsiveness to change. This study
      examined responsiveness, minimal important difference (MID), test-retest
      reliability, and construct validity of the 2MWT in people with stable COPD
      attending outpatient pulmonary rehabilitation (PR). METHODS: At pre-PR
      assessment, study participants completed a 2MWT twice in addition to usual
      measures (6MWT and Chronic Respiratory Questionnaire). At post-PR assessment
      following a standard PR program, measures were repeated and global rating of
      change scores obtained (patient and therapist). Pre-post program change scores
      were examined for correlations with change in 2-minute walk distance (2MWD) and
      used (where r>=0.3) to estimate the MID through anchor-based methods.
      Distribution-based estimates based on standard error of measurement were
      examined. Test-retest reliability (intraclass correlation coefficient [ICC] and
      Bland-Altman agreement) and validity (Pearson correlation with 6-minute walk
      distance [6MWD]) were reported. RESULTS: Fifty-nine people (28 men) with stable
      COPD, mean age 68 years (SD 10 years), and percentage predicted forced expiratory
      volume in 1 second 48% (SD 20%) attended pre-PR assessment. Test-retest ICC for
      same-session 2MWD was 0.985. A mean difference of 2.4 m (95% confidence interval
      [CI] 0.7-4.0 m, P=0.006) occurred between the first and second trials. 2MWD and
      6MWD were highly correlated (r=0.87, P<0.001). Forty-one participants completed
      PR and were included in responsiveness and MID analysis. Mean 2MWD improved
      significantly post-PR (8.8 m, 95% CI 3.6-14 m, P=0.001). The MID in 2MWD,
      anchored against clinically meaningful change in 6MWD, was 5.5 m (area under
      curve =0.81, P=0.001). Distribution-based methods estimated an MID of 4 m.
      CONCLUSION: Change in 2MWD of at least 5.5 m following a PR program corresponded
      to a clinically meaningful change. A practice test is recommended due to learning
      effects.

PMID- 29070947
TI  - A case series of an off-the-shelf online health resource with integrated nurse
      coaching to support self-management in COPD.
AB  - BACKGROUND: COPD has significant psychosocial impact. Self-management support
      improves quality of life, but programs are not universally available. IT-based
      self-management interventions can provide home-based support, but have mixed
      results. We conducted a case series of an off-the-shelf Internet-based health
      promotion program, The Preventive Plan (TPP), coupled with nurse-coach support,
      which aimed to increase patient activation and provide self-management benefits.
      MATERIALS AND METHODS: A total of 19 COPD patients were recruited, and 14
      completed 3-month follow-up in two groups: groups 1 and 2 with more and less
      advanced COPD, respectively. Change in patient activation was determined with
      paired t-tests and Wilcoxon signed-rank tests. Benefits and user experience were
      explored in semistructured interviews, analyzed thematically. RESULTS: Only group
      1 improved significantly in activation, from a lower baseline than group 2; group
      1 also improved significantly in mastery and anxiety. Both groups felt
      significantly more informed about COPD and reported physical functioning
      improvements. Group 1 reported improvements in mood and confidence. Overall,
      group 2 reported fewer benefits than group 1. Both groups valued nurse-coach
      support; for group 1, it was more important than TPP in building confidence to
      self-manage. The design of TPP and lack of motivation to use IT were barriers to
      use, but disease severity and poor IT skills were not. DISCUSSION: Our findings
      demonstrate the feasibility of combining nurse-coach support aligned to an
      Internet-based health resource, TPP, in COPD and provide learning about the
      challenges of such an approach and the importance of the nurse-coach role.

PMID- 29070948
TI  - Antibacterial activity of gold nanorods against Staphylococcus aureus and
      Propionibacterium acnes: misinterpretations and artifacts.
AB  - The antibacterial activity of gold nanorod (GNR) suspensions of different surface
      functionalities was investigated against standard strains of Staphylococcus
      aureus and Propionibacterium acnes, taking into consideration two commonly
      "overlooked" factors: the colloidal stability of GNR suspensions upon mixing with
      bacterial growth media and the possible contribution of "impurities/molecules" in
      GNR suspensions to the observed antibacterial activity. The results demonstrated
      that cationic polyallylamine hydrochloride (PAH)-GNR were severely aggregated
      when exposed to bacterial growth media compared to other GNR suspensions. In
      addition, the free cetyltrimethylammonium bromide (CTAB) present in GNR
      suspensions is most likely the origin of the observed antibacterial activity.
      However, the antibacterial activity of GNR themselves could not be excluded.
      Probing these two critical control studies prevents misinterpretations and
      artifacts of the antibacterial activity of nanoparticles. Unfortunately, these
      practices are usually ignored in the published studies and may explain the
      significant conflicting results. In addition, this study indicates that GNR could
      be a promising candidate for the treatment of skin follicular diseases such as
      acne vulgaris.

PMID- 29070949
TI  - Optimization and physicochemical characterization of a cationic lipid
      phosphatidylcholine mixed emulsion formulated as a highly efficient vehicle that
      facilitates adenoviral gene transfer.
AB  - Cationic lipid-based nanoparticles enhance viral gene transfer by forming
      electrostatic complexes with adenoviral vectors. We recently demonstrated the
      superior complexation capabilities of 1,2-dioleoyl-3-trimethylammonium propane
      (DOTAP) emulsion compared with a liposomal counterpart but the cytotoxicity of
      DOTAP emulsions remained a challenge. The present study is aimed at formulating
      an emulsion capable of acting as a highly effective viral gene transfer vehicle
      with reduced cytotoxicity and to physicochemically characterize the structures of
      virus-emulsion complexes in comparison with virus-liposome complexes when the
      only difference between emulsions and liposomes was the presence or absence of
      inner oil core. The emulsion formulation was performed by 1) reducing the content
      of DOTAP while increasing the content of zwitterionic lipid 1,2-dimyristoyl-sn
      glycero-3-phosphocholine (DMPC), and 2) optimizing the oil content. The
      complexation capability of formulated DOTAP:DMPC mixed emulsions was similar to
      those of emulsions containing DOTAP alone while displaying significantly lower
      cytotoxicity. The complexation capabilities of the DOTAP:DMPC mixed emulsion were
      serum-compatible and were monitored in a variety of cell types, whereas its
      liposomal counterpart was totally ineffective. Characterization by scanning
      electron microscopy, transmission electron microscopy, atomic force microscopy,
      and dynamic light scattering studies indicated that the optimized emulsions
      spontaneously surrounded the virus particles to generate emulsions that
      encapsulated the viral particles, whereas viral particles merely attached to the
      surfaces of the counterpart liposomes to form multiviral aggregates. Overall,
      these studies demonstrated that optimized DOTAP:DMPC mixed emulsions are
      potentially useful for adenoviral gene delivery due to less cytotoxicity and the
      unique ability to encapsulate the viral particle, highlighting the importance of
      nanoparticle formulation.

PMID- 29070950
TI  - Periodontal ligament injection versus routine local infiltration for nonsurgical
      single posterior maxillary permanent tooth extraction: comparative double-blinded
      randomized clinical study.
AB  - AIM: The aim of this study was to evaluate the efficacy of, and patients'
      subjective responses to, periodontal ligament (PDL) anesthetic injection compared
      to traditional local-anesthetic infiltration injection for the nonsurgical
      extraction of one posterior maxillary permanent tooth. MATERIALS AND METHODS: All
      patients scheduled for nonsurgical symmetrical maxillary posterior permanent
      tooth extraction in the Department of Oral and Maxillofacial Surgery at the
      University of Jordan Hospital, Amman, Jordan over a 7-month period were invited
      to participate in this prospective randomized double-blinded split-mouth study.
      Every patient received the recommended volume of 2% lidocaine with 1:100,000
      epinephrine for PDL injection on the experimental side and for local infiltration
      on the control side. A visual analog scale (VAS) and verbal rating scale (VRS)
      were used to describe pain felt during injection and extraction, respectively.
      Statistical significance was based on probability values <0.05 and measured using
      chi2 and Student t-tests and nonparametric Mann-Whitney and Kruskal-Wallis tests.
      RESULTS: Of the 73 patients eligible for this study, 55 met the inclusion
      criteria: 32 males and 23 females, with a mean age of 34.87+/-14.93 years.
      Differences in VAS scores and VRS data between the two techniques were
      statistically significant (P<0.001) and in favor of the infiltration injection.
      CONCLUSION: The PDL injection may not be the alternative anesthetic technique of
      choice to routine local infiltration for the nonsurgical extraction of one
      posterior maxillary permanent tooth.

PMID- 29070951
TI  - Agreement between calcaneal quantitative ultrasound and osteoporosis self
      assessment tool for Asians in identifying individuals at risk of osteoporosis.
AB  - BACKGROUND: Calcaneal quantitative ultrasound (QUS) is a useful tool in
      osteoporosis screening. However, QUS device may not be available at all primary
      health care settings. Osteoporosis self-assessment tool for Asians (OSTA) is a
      simple algorithm for osteoporosis screening that does not require any
      sophisticated instruments. This study explored the possibility of replacing QUS
      with OSTA by determining their agreement in identifying individuals at risk of
      osteoporosis. METHODS: A cross-sectional study was conducted to recruit Malaysian
      men and women aged >=50 years. Their bone health status was measured using a
      calcaneal QUS device and OSTA. The association between OSTA and QUS was
      determined using Spearman's correlation and their agreement was assessed using
      Cohen Kappa and receiver-operating curve. RESULTS: All QUS indices correlated
      significantly with OSTA (p<0.05). The agreement between QUS and OSTA was minimal
      but statistically significant (p<0.05). The performance of OSTA in identifying
      subjects at risk of osteoporosis according to QUS was poor-to-fair in women
      (p<0.05), but not statistically significant for men (p>0.05). Changing the cut
      off values improved the performance of OSTA in women but not in men. CONCLUSION:
      The agreement between QUS and OSTA is minimal in categorizing individuals at risk
      of osteoporosis. Therefore, they cannot be used interchangeably in osteoporosis
      screening.

PMID- 29070952
TI  - let-7d suppresses proliferation and invasion and promotes apoptosis of meningioma
      by targeting AEG-1.
AB  - BACKGROUND: let-7d has been indicated to act as a tumor suppressor in various
      cancers. However, the function and molecular mechanism of let-7d in meningioma
      progression have not been elucidated. MATERIALS AND METHODS: Quantitative real
      time polymerase chain reaction (qRT-PCR) was performed to detect the expression
      levels of let-7d and AEG-1 mRNA in meningioma tissues and cell lines. The protein
      level of AEG-1 was measured by Western blot analysis. MTT assay, Transwell
      invasion assay and flow cytometry analysis were carried out to determine the
      proliferation, invasion and apoptosis of IOMM-Lee and CH-157MN cells,
      respectively. Target gene of let-7d was verified by luciferase reporter analysis.
      RESULTS: let-7d expression was downregulated, and AEG-1 expression was
      upregulated in meningioma tumor tissues. let-7d overexpression suppressed
      proliferation and invasion and induced apoptosis in IOMM-Lee and CH-157MN cells.
      Moreover, AEG-1 was a direct target of let-7d. Restoration of AEG-1 expression
      reversed let-7d-mediated suppression of the proliferation and invasion and let-7d
      induced apoptosis in IOMM-Lee and CH-157MN cells. CONCLUSION: let-7d repressed
      proliferation and invasion and promoted apoptosis of meningioma cells by
      targeting AEG-1. The present study provided a better understanding of the
      meningioma pathogenesis and a promising therapeutic target for meningioma
      patients.

PMID- 29070946
TI  - Joint statement for the diagnosis, management, and prevention of chronic
      obstructive pulmonary disease for Gulf Cooperation Council countries and Middle
      East-North Africa region, 2017.
AB  - Smoking and subsequent development of COPD is an ever-increasing epidemic in
      Arabian Gulf and Middle East countries, with no signs of decline. The important
      fact to be highlighted is that this COPD epidemic of increasing incidence and
      prevalence is mostly unrecognized by patients, due to the common attribution of
      symptoms to "smoker's cough", and the underdiagnosis and undertreatment by
      physicians because the common signs and symptoms masquerade as asthma.
      Consequently, there are long-term adverse effects of missing the diagnosis. The
      purpose of this review article is to focus upon the status of COPD in Arabian
      Gulf and Middle East countries, stressing the increasing burden of smoking and
      COPD, to emphasize the specific factors leading to rise in prevalence of COPD, to
      bring to light the underdiagnosis and undermanagement of COPD, and to treat COPD
      in conformity with standard guidelines with local and regional modifications.
      This review ends with suggestions and recommendations to the health department to
      formulate policies and to generate awareness among the general public about the
      side effects of smoking and consequences of COPD.

PMID- 29070954
TI  - Race predictors and hemodynamic alteration after an ultra-trail marathon race.
AB  - OBJECTIVE: Unique rough-terrain ultra-trail running races have increased in
      popularity. Concerns regarding the suitability of the candidates make it
      difficult for organizers to manage safety regulations. The purpose of this study
      was to identify possible race predictors and assess hemodynamic change after long
      endurance races. METHODS: We studied 228 runners who competed in a 66 km-trail
      running race. A questionnaire and noninvasive hemodynamic flow assessment
      including blood pressure, heart rate, stroke volume, stroke volume variation,
      systemic vascular resistance, cardiac index, and oxygen saturation were used to
      determine physiologic alterations and to identify finish predictors. One hundred
      and thirty volunteers completed the questionnaire, 126 participants had a prerace
      hemodynamic assessment, and 33 of these participants completed a postrace
      assessment after crossing the finish line. The participants were divided into a
      finisher group and a nonfinisher group. RESULTS: The average age of all runners
      was 37 years (range of 24-56 years). Of the 228 runners, 163 (71.5%) were male.
      There were 189 (82.9%) finishers. Univariable analysis indicated that the finish
      predictors included male gender, longest distance ever run, faster running
      records, and lower diastolic pressure. Only a lower diastolic pressure was a
      significant predictor of race finishing (diastolic blood pressure 74-84 mmHg:
      adjusted odd ratio 3.81; 95% confidence interval [CI] =1.09-13.27 and diastolic
      blood pressure <74 mmHg: adjusted odd ratio 7.74; 95% CI =1.57-38.21) using the
      figure from the multivariable analysis. Among the finisher group, hemodynamic
      parameters showed statistically significant differences with lower systolic blood
      pressure (135.9+/-14.8 mmHg vs 119.7+/-11.3 mmHg; p<0.001), faster heart rate
      (72.6+/-10.7 bpm vs 96.4+/-10.4 bpm; p<0.001), lower stroke volume (43.2+/-13.6
      mL vs 29.3+/-10.1 mL; p<0.001), higher stroke volume variation; median
      (interquartile range) (36% [25%-58%] vs 53% [33%-78%]; p<0.001), and lower oxygen
      saturation (97.4%+/-1.0% vs 96.4%+/-1.0%; p<0.001). Systemic vascular resistance
      and cardian index did not change significantly. CONCLUSION: The only race
      finishing predictor from the multivariable analysis was lower diastolic pressure.
      Finishers seem to have a hypovolemic physiologic response and a lower level of
      oxygen saturation.

PMID- 29070956
TI  - The role of secure attachment, empathic self-efficacy, and stress perception in
      causal beliefs related to mental illness - a cross-cultural study: Italy versus
      Israel.
AB  - BACKGROUND: Research suggests that "mental illness etiological beliefs" and
      attitudes toward mentally ill people are significantly related; it has also been
      demonstrated that adult attachment style and empathic self-efficacy affect such
      attitudes. Moreover, community or regional culture has a significant impact on
      etiology beliefs and attitudes toward the mentally sick. MATERIALS AND METHODS:
      We carried out this study in Italy and Israel among psychology students to
      compare two cultures in regards to causal beliefs of mental disorders and the
      roles that specific variables, such as secure attachment, empathic self-efficacy,
      and stress, play in etiological beliefs. The participants (N=305) were students
      who belonged to two universities: Padua (N=183) and Haifa (N=122). The Many Facet
      Rasch Model (MFRM) was applied in a cross-cultural perspective to analyze the
      differential functioning of specific etiological beliefs in relation to the above
      mentioned variables; the effect of gender and religious beliefs was also entered
      in the MFRM. RESULTS: The two cultures reacted differently to the biogenetic and
      psychosocial causal explanations of mental disorders: Israeli students endorsed
      the biogenetic causal beliefs model more frequently than the Italians. Among
      other findings, concerning the biogenetic model, the Italian students were
      predominantly males, who declared to be religious and reported lower levels of
      secure attachment than Israelis. On the other hand, the Israeli students who
      manifested a preference toward the biogenetic explanation were mostly females,
      who declared not to be religious and who manifested higher levels of secure
      attachment than the Italians. CONCLUSION: This article is expected to contribute
      to the improvement of the understanding of general public's etiological beliefs
      of mental illness. Similarities and differences between the two cultures, Israel
      and Italy, have been highlighted on the basis of the MFRM analysis. The effect
      that interpersonal relations, such as attachment style, perceived empathy, and
      stress, have on etiological beliefs was also investigated.

PMID- 29070953
TI  - Vulvodynia: a consideration of clinical and methodological research challenges
      and recommended solutions.
AB  - Vulvodynia, an idiopathic chronic vulvar pain, is a prevalent genital pain
      condition that results in significant impairment to sexual, relational, and
      psychological functioning of affected women and their romantic partners. Despite
      its high prevalence, there remain gaps in knowledge and health care access for
      women coping with vulvodynia, given its varied clinical presentation and no
      widely accepted treatment protocol. The past several decades have seen important
      advancements in understanding vulvodynia and developing effective treatments;
      however, progress has been impeded due to clinical and methodological challenges
      in conducting research with this vulnerable population. This review presents a
      brief overview of vulvodynia correlates, consequences, etiology, and treatment,
      and then turns its attention to considering the clinical and methodological
      challenges that hinder vulvodynia research. Identifying these barriers alongside
      potential mitigating solutions is essential to developing empirically supported
      treatments for all women affected by vulvodynia, across all age and minority
      groups. Potential solutions will require researchers to broaden eligibility
      criteria, examine subgroups of women, and expand definitions of treatment
      outcomes, and may be best facilitated by more active collaboration among research
      groups and across relevant disciplines. Engagement in these solutions may
      contribute to more representative findings and the development and dissemination
      of empirically based treatment options for this complex pain condition.

PMID- 29070958
TI  - Flipped learning: should it replace didactic learning?

PMID- 29070957
TI  - EGFR T790M: revealing the secrets of a gatekeeper.
AB  - Non-small-cell lung cancers that harbor activating mutations in the EGFR gene
      represent an important molecularly defined subset of lung cancer. Despite
      dramatic initial responses with first- and second-generation EGFR-directed
      tyrosine-kinase inhibitors (TKIs) against these cancers, the development of a
      dominant and frequent resistance mechanism through a threonine-methionine amino
      acid substitution at position 790 (T790M) of EGFR has limited the long-term
      efficacy of these targeted therapies. This "gatekeeper" EGFR T790M alteration
      remains the only validated and relevant second-site resistance mutation for EGFR,
      allowing for focused research to understand and overcome EGFR T790M-mediated
      resistance. The current review focuses on EGFR T790M by discussing mechanisms of
      resistance mediated by EGFR T790M, reviewing development of novel third
      generation EGFR TKIs targeting EGFR T790M, and highlighting current research on
      overcoming resistance to third-generation EGFR T790M TKIs.

PMID- 29070955
TI  - Patellofemoral pain in athletes: clinical perspectives.
AB  - Patellofemoral pain (PFP) is a very common problem in athletes who participate in
      jumping, cutting and pivoting sports. Several risk factors may play a part in the
      pathogenesis of PFP. Overuse, trauma and intrinsic risk factors are particularly
      important among athletes. Physical examination has a key role in PFP diagnosis.
      Furthermore, common risk factors should be investigated, such as hip muscle
      dysfunction, poor core muscle endurance, muscular tightness, excessive foot
      pronation and patellar malalignment. Imaging is seldom needed in special cases.
      Many possible interventions are recommended for PFP management. Due to the
      multifactorial nature of PFP, the clinical approach should be individualized, and
      the contribution of different factors should be considered and managed
      accordingly. In most cases, activity modification and rehabilitation should be
      tried before any surgical interventions.

PMID- 29070959
TI  - Validation of a PCR test to predict the presence of flavor volatiles mesifurane
      and gamma-decalactone in fruits of cultivated strawberry (Fragaria * ananassa).
AB  - Flavor improvement is currently one of the most important goals for strawberry
      breeders. At the same time, it is one of the most complex traits to improve,
      involving the balanced combination of several desired characteristics such as
      high sweetness, moderate acidity, and the appropriate combination of aroma
      compounds that are beginning to be delineated in consumer tests. DNA-informed
      breeding will expedite the selection of complex traits, such as flavor, over
      traditional phenotypic evaluation, particularly when markers linked to several
      traits of interests are combined during the breeding process. Natural variation
      in mesifurane and gamma-decalactone, two key volatile compounds providing sweet
      Sherry and fresh peach-like notes to strawberry fruits, is controlled by the
      FaOMT and FaFAD1 genes, respectively. In this study, we have optimized a simple
      PCR test for combined analysis of these genes and determined a prediction
      accuracy above 91% using a set of 71 diverse strawberry accessions. This high
      accuracy in predicting the presence of these important volatiles combined with
      the simplicity of the analytical methodology makes this DNA test an efficient
      tool for its implementation in current strawberry-breeding programs for the
      selection of new strawberry cultivars with superior flavor.

PMID- 29070960
TI  - Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment
      Planning System (TPS): TrueBeamTM millennium 120 leaf MLC.
AB  - AIM: Objective of present study is to determine optimum value of DLG and its
      validation prior to being incorporated in TPS for Varian TrueBeamTM millennium
      120 leaves MLC. BACKGROUND: Partial transmission through the rounded leaf ends of
      the Multi Leaf Collimator (MLC) causes a conflict between the edges of the light
      field and radiation field. Parameter account for this partial transmission is
      called Dosimetric Leaf Gap (DLG). The complex high precession technique, such as
      Intensity Modulated Radiation Therapy (IMRT), entails the modeling of optimum
      value of DLG inside Eclipse Treatment Planning System (TPS) for precise dose
      calculation. MATERIALS AND METHODS: Distinct synchronized uniformed extension of
      sweeping dynamic MLC leaf gap fields created by Varian MLC shaper software were
      use to determine DLG. DLG measurements performed with both 0.13 cc semi-flex
      ionization chamber and 2D-Array I-Matrix were used to validate the DLG;
      similarly, values of DLG from TPS were estimated from predicted dose. Similar
      mathematical approaches were employed to determine DLG from delivered and TPS
      predicted dose. DLG determined from delivered dose measured with both ionization
      chamber (DLGIon) and I-Matrix (DLGI-Matrix) compared with DLG estimate from TPS
      predicted dose (DLGTPS). Measurements were carried out for all available 6MV,
      10MV, 15MV, 6MVFFF and 10MVFFF beam energies. RESULTS: Maximum and minimum DLG
      deviation between measured and TPS calculated DLG was found to be 0.2 mm and 0.1
      mm, respectively. Both of the measured DLGs (DLGIon and DLGI-Matrix) were found
      to be in a very good agreement with estimated DLG from TPS (DLGTPS). CONCLUSIONS:
      Proposed method proved to be helpful in verifying and validating the DLG value
      prior to its clinical implementation in TPS.

PMID- 29070961
TI  - The Trajectory of Concurrent Motor and Vocal Behaviors Over the Transition to
      Crawling in Infancy.
AB  - To document the trajectory of motor and vocal behaviors in real and developmental
      time, researchers observed infants at each of 4 biweekly naturalistic play
      sessions over the transition to crawling. An exhaustive and mutually exclusive
      coding scheme documented every vocalization and posture. Odds ratios of the
      likelihood of a given posture-vocalization dyad revealed that vocalization and
      crawling were significantly unlikely to co-occur at the session marking the onset
      of crawling. Infants' allocation of attention over the transition to crawling
      prompted behavioral trade-offs. During mastery of a novel skill, infants had
      difficulty allocating attention to multiple tasks, but with experience a decrease
      in attentional load for the new skill allowed performance of simultaneous
      behaviors in other domains to occur.

PMID- 29070962
TI  - Mindfulness in Motion for People with Multiple Sclerosis: A Feasibility Study.
AB  - BACKGROUND: Mindfulness in Motion is an 8-week mindfulness-based intervention
      that uses yoga movement, mindfulness meditation, and relaxing music. This study
      examined the feasibility of using Mindfulness in Motion in people with multiple
      sclerosis (MS) and the effect of this program on stress, anxiety, depression,
      fatigue, and quality of life in people with MS. METHODS: Twenty-two people with
      MS completed the 8-week mindfulness program as well as assessments 1 week before
      and after the intervention. RESULTS: Pre/post comparison of four self-reported
      questionnaires-the Mental Health Inventory, 36-item Short Form Health Status
      Survey, Modified Fatigue Impact Scale, and Five Facet Mindfulness Questionnaire
      showed significant improvement in physical functioning, vitality, and mental
      health. Specifically, improvements were seen in anxiety, depression, and positive
      affect; cognitive, psychosocial, and overall functioning regarding fatigue; and
      mindfulness in the areas of observing, acting with awareness, nonjudgment, and
      nonreactivity. CONCLUSIONS: Due to the uncertainty in disease progression
      associated with MS, and the multiplicity of mental and physical symptoms
      associated with it, programming that addresses anxiety, depression, and fatigue
      is a key area of future research in MS disease management. Mindfulness in Motion
      proved to be a feasible program yielding positive results, supporting the need
      for research to determine the extent to which the program can improve quality-of
      life outcomes for people with MS.

PMID- 29070963
TI  - Relationship Between Fatigability and Perceived Fatigue Measured Using the
      Neurological Fatigue Index in People with Multiple Sclerosis.
AB  - BACKGROUND: Understanding the relationship between perceived fatigue and
      performance fatigability could lead to more effective interventions to manage
      multiple sclerosis (MS)-related fatigue. However, the relationship between self
      perceived fatigue measured using the Neurological Fatigue Index (NFI-MS) and
      performance fatigability in people with MS is unknown. We sought to explore the
      relationship between the NFI-MS and performance fatigability in people with MS.
      METHODS: Fifty-two participants (mean +/- SD age, 46.8 +/- 10.1 years) completed
      the study. Three measures of performance fatigability were used: percent change
      in meters walked from first to last minute of the 6-Minute Walk Test, percent
      change in force exerted from first to last trial on a repetitive maximal hand
      grip test, and response speed variability on the Continuous Performance Test.
      Perceived physical and cognitive fatigue were measured using the NFI-MS. The
      state level of fatigue was examined immediately before and after performing the
      fatigability measures using a one-item visual analogue fatigue scale. RESULTS: Of
      the three performance fatigability measures, only the attentional task (response
      speed variability) was significantly associated with NFI-MS physical (r = 0.326,
      P = .020) and cognitive (r = 0.276, P = .050) domain scores. Participants
      demonstrated significantly higher state levels of fatigue after performing all
      performance fatigability measures (P <= .001). CONCLUSIONS: The NFI-MS and the
      performance fatigability measures used in this study are easy to administer. We
      encourage wider use of these measures in clinical and research settings for
      comprehensive assessment of MS-related fatigue.

PMID- 29070964
TI  - Trigeminal Neuralgia Commonly Precedes the Diagnosis of Multiple Sclerosis.
AB  - BACKGROUND: Trigeminal neuralgia (TN) is a well-recognized cause of facial pain
      in the general population, and multiple sclerosis (MS) accounts for some of these
      cases. However, the prevalence of TN in MS is poorly understood. We investigated
      the prevalence of TN and how often TN is the initial presentation of MS in a
      large MS cohort. METHODS: In 2009, we surveyed participants in the North America
      Research Committee on Multiple Sclerosis Registry regarding TN, including date of
      onset and pharmacologic and nonpharmacologic treatments used. We estimated the
      frequency of TN and the frequency with which TN preceded the diagnosis of MS. We
      compared the demographic and clinical characteristics of participants who
      reported TN with those of participants who did not using descriptive statistics
      and logistic regression. RESULTS: Among 8590 eligible survey respondents, the
      prevalence of TN was 830 (9.7%). Of these respondents, 588 reported the year when
      TN was diagnosed. The diagnosis of TN preceded that of MS in 88 respondents
      (15.0%), and the mean +/- SD age at diagnosis of TN was 45.3 +/- 11.0 years. The
      odds of reporting TN were higher in women and those with greater disability and
      longer disease duration. Pharmacologic treatments were used by 88.3% of
      respondents; 9.7% underwent surgical interventions. CONCLUSIONS: In MS, TN occurs
      frequently and precedes the diagnosis of MS in 15.0% of individuals. Given the
      frequency of TN in MS, further epidemiological studies and clinical trials to
      identify effective pharmacologic and nonpharmacologic therapies for TN in MS are
      warranted.

PMID- 29070965
TI  - Validity and Reliability of Four Clinical Gait Measures in Patients with Multiple
      Sclerosis.
AB  - BACKGROUND: The gold standards for assessing ambulation are the Expanded
      Disability Status Scale (EDSS) and the Timed 25-Foot Walk (T25FW) test. In
      relation with these measures, we assessed the reliability and validity of four
      clinical gait measures: the Timed Up and Go (TUG) test, the Dynamic Gait Index
      (DGI), the 2-Minute Walk Test (2MWT), and the 6-Minute Walk Test (6MWT). Patient
      self-report of gait was also assessed using the 12-item Multiple Sclerosis
      Walking Scale (MSWS-12). METHODS: Individuals 20 years or older with a diagnosis
      of multiple sclerosis (MS) and an EDSS score of 2.0 to 6.5 completed the MSWS-12,
      T25FW test, TUG test, DGI, 2MWT, and 6MWT. All the tests were repeated 2 weeks
      later at the same time of day to establish their reliability and concurrent
      validity. Predictive validity was established using the EDSS. RESULTS: Forty-two
      patients with MS were included. All measures showed high test-retest reliability.
      The TUG test, 2MWT, and 6MWT were significantly correlated with the T25FW test
      (Spearman rho = -0.902, -0.919, and -0.905, respectively). The EDSS was also
      significantly correlated with all the walking tests. The MSWS-12 demonstrated the
      highest correlation to the EDSS (rho = 0.788). CONCLUSIONS: The TUG test, the
      DGI, the 2MWT, and the 6MWT exhibited strong psychometric properties and were
      found to be significant predictors of the EDSS score. Use of these tests to
      prospectively monitor the effects of medical and rehabilitation treatment should
      be considered in the comprehensive care of patients with MS.

PMID- 29070967
TI  - Case Report: Glatiramer Acetate-Induced Serum Sickness.
AB  - Multiple sclerosis (MS) is a central nervous system demyelinating disease with a
      prevalence of approximately 400,000 individuals in the United States. Glatiramer
      acetate is a frequently prescribed disease-modifying therapy used for the
      management of relapsing forms of the disease. A 40-year-old woman with relapsing
      remitting MS presented with symptomatic concerns of vomiting, fever, diffuse
      rash, joint and low back pain, and distal lower-limb paresthesia and was
      subsequently admitted to the hospital for investigation and treatment. She was
      discharged initially after conservative management with intravenous
      methylprednisolone and diphenhydramine. She was restarted on glatiramer acetate 3
      weeks later and required rehospitalization for similar symptoms 3 days after
      resumption of the disease-modifying therapy and was diagnosed as having serum
      sickness.

PMID- 29070966
TI  - Psychometric Properties of a Clinical Strength Assessment Protocol in People with
      Multiple Sclerosis.
AB  - BACKGROUND: Strength training in people with multiple sclerosis (MS) is an
      important component of rehabilitation, but it can be challenging for clinicians
      to quantify strength accurately and reliably. This study investigated the
      psychometric properties of a clinical strength assessment protocol using handheld
      dynamometry and other objective, quantifiable tests for the lower extremities and
      trunk in people with MS. METHODS: This study determined discriminant validity
      between 25 participants with MS and 25 controls and between participants with MS
      who had higher versus lower disability; test-retest reliability across 7 to 10
      days; and response stability. The protocol included handheld dynamometry
      measurements of ankle dorsiflexion, knee flexion and extension; hip flexion,
      extension, abduction, and adduction; and trunk lateral flexion. Muscular
      endurance tests were used to measure trunk extension, trunk flexion, and ankle
      plantarflexion. RESULTS: The protocol discriminated between participants with MS
      and controls for all muscles tested (P < .001-.003). The protocol also
      discriminated between low- and moderate-disability groups (P = .001-.046) for 80%
      of the muscles tested. Test-retest reliability intraclass correlation
      coefficients were high (0.81-0.97). Minimal detectable change as a percentage of
      the mean was 13% to 36% for 85% of muscles tested. CONCLUSIONS: This study
      provides evidence for the discriminant validity, test-retest reliability, and
      response stability of a strength assessment protocol in people with MS. This
      protocol may be useful for tracking outcomes in people with MS for clinical
      investigations and practice.

PMID- 29070969
TI  - Editorial.

PMID- 29070971
TI  - Variability extraction and modeling for product variants.
AB  - Fast-changing hardware and software technologies in addition to larger and more
      specialized customer bases demand software tailored to meet very diverse
      requirements. Software development approaches that aim at capturing this
      diversity on a single consolidated platform often require large upfront
      investments, e.g., time or budget. Alternatively, companies resort to developing
      one variant of a software product at a time by reusing as much as possible from
      already-existing product variants. However, identifying and extracting the parts
      to reuse is an error-prone and inefficient task compounded by the typically large
      number of product variants. Hence, more disciplined and systematic approaches are
      needed to cope with the complexity of developing and maintaining sets of product
      variants. Such approaches require detailed information about the product
      variants, the features they provide and their relations. In this paper, we
      present an approach to extract such variability information from product
      variants. It identifies traces from features and feature interactions to their
      implementation artifacts, and computes their dependencies. This work can be
      useful in many scenarios ranging from ad hoc development approaches such as clone
      and-own to systematic reuse approaches such as software product lines. We applied
      our variability extraction approach to six case studies and provide a detailed
      evaluation. The results show that the extracted variability information is
      consistent with the variability in our six case study systems given by their
      variability models and available product variants.

PMID- 29070968
TI  - Predictors of Mortality in Veterans with Multiple Sclerosis in an Outpatient
      Clinic Setting.
AB  - BACKGROUND: Examining factors that increase risk of death in veterans with
      multiple sclerosis (MS) may help reduce MS-related mortality. We sought to
      determine predictors of mortality in veterans with MS attending an outpatient
      clinic. METHODS: Review of electronic medical records of 226 veterans with MS
      regularly followed up from January 1, 2000, through December 31, 2014. RESULTS:
      Mortality at the end of the 15-year study period was 14%. Patients with MS died
      prematurely, with a standardized mortality rate of 1.35 relative to the general
      (Oklahoma) population. The main causes of death documented were MS disease itself
      (57% of cases), infection (43%), and cancer and respiratory failure (18% each).
      Cox regression analysis using the whole cohort showed that progressive MS type;
      older age at entry into the study; presence of sensory, cerebellar, or motor
      (weakness and/or ataxia) concerns on presentation; more disability on
      presentation; higher body-mass index; being diabetic; never received disease
      modifying therapy; and presence of pressure ulcers or neurogenic bladder were
      significant predictors of higher mortality. CONCLUSIONS: Initial presentation by
      MS type (progressive MS), higher level of disability, and associated motor,
      sensory, and cerebellar concerns are significant predictors of MS-related
      mortality. The main causes of death were MS disease itself, infection,
      respiratory disease, and cancer. More attention should be given to preventive
      strategies that delay mortality, such as yearly immunization and aggressively
      treating MS-related complications and diabetes mellitus.

PMID- 29070972
TI  - Congress of the German Society of Transfusion Medicine and Immunohematology -
      50th Anniversary.

PMID- 29070970
TI  - Polyp Resection and Removal Procedures: Insights From the 2017 Digestive Disease
      Week.
AB  - Colorectal cancer (CRC) is an important public health issue not only because of
      its high incidence but also for its high mortality rate. When CRC is diagnosed at
      an early stage, the 5-year relative survival rate reaches 89.9%. However, only
      39% of patients with CRC are diagnosed at this stage. Screening decreases both
      the incidence of CRC and the number of CRC-related deaths. There are several
      options available for screening, and colonoscopy is one of the most common
      methods utilized in the United States. Screening colonoscopy is associated with
      durable protection from CRC. However, it has become increasingly apparent in
      recent years that polyp detection and resection have not been completely
      effective in clinical practice. Because the protective benefit of colonoscopy is
      variable, quality benchmarks have been established to improve its clinical
      effectiveness. The adenoma detection rate (ADR) directly correlates with the
      incidence and mortality of postcolonoscopy (or interval) CRCs. It is now routine
      to remove large polyps (>=20 mm) using advanced techniques for endoscopic mucosal
      resection (EMR) and endoscopic submucosal dissection (ESD). Recent studies have
      helped identify which colorectal lesions are at higher risk of invasive cancer
      and would benefit from a complete en bloc resection. Such data may guide
      endoscopists in making a decision on whether to use ESD or EMR for removal of
      large lesions. An increased number of studies have reported on the efficacy and
      safety of cold snare resection, even for larger polyps. These data suggest that
      cold snare resection may be as effective, and perhaps safer, than hot snare
      resection for polyps up to 1 to 2 cm in size. However, data on the threshold for
      cold snare resection and the value of submucosal injectates are still lacking.
      Use of submucosal injection is generally preferred for larger polyps,
      particularly those located in the proximal colon, where the colonic wall is
      thinner.

PMID- 29070973
TI  - Antibody Engineering - Tailor-Made Next Generation Antibodies by Molecular
      Design.

PMID- 29070974
TI  - An Fc Double-Engineered CD20 Antibody with Enhanced Ability to Trigger Complement
      Dependent Cytotoxicity and Antibody-Dependent Cell-Mediated Cytotoxicity.
AB  - BACKGROUND: Engineering of the antibody's fragment crystallizable (Fc) by
      modifying the amino acid sequence (Fc protein engineering) or the glycosylation
      pattern (Fc glyco-engineering) allows enhancing effector functions of tumor
      targeting antibodies. Here, we investigated whether complement-dependent
      cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) of
      CD20 antibodies could be improved simultaneously by combining Fc protein
      engineering and glyco-engineering technologies. METHODS AND RESULTS: Four
      variants of the CD20 antibody rituximab were generated: a native IgG1, a variant
      carrying the EFTAE modification (S267E/H268F/S324T/G236A/I332E) for enhanced CDC
      as well as glyco-engineered, non-fucosylated derivatives of both to boost ADCC.
      The antibodies bound CD20 specifically with similar affinity. Antibodies with
      EFTAE modification were more efficacious in mediating CDC, irrespective of
      fucosylation, than antibodies with wild-type sequences due to enhanced C1q
      binding. In contrast, non-fucosylated variants had an enhanced affinity to
      FcgammaRIIIA and improved ADCC activity. Importantly, the double-engineered
      antibody lacking fucose and carrying the EFTAE modification mediated both CDC and
      ADCC with higher efficacy than the native CD20 IgG1 antibody. CONCLUSION:
      Combining glyco-engineering and protein engineering technologies offers the
      opportunity to simultaneously enhance ADCC and CDC activities of therapeutic
      antibodies. This approach may represent an attractive strategy to further improve
      antibody therapy of cancer and deserves further evaluation.

PMID- 29070975
TI  - Human Antibody Fusion Proteins/Antibody Drug Conjugates in Breast and Ovarian
      Cancer.
AB  - Considerable research efforts have been dedicated to understanding ovarian and
      breast cancer mechanisms, but there has been little progress translating the
      research into effective clinical applications. Hence, personalized/precision
      medicine has emerged because of its potential to improve the accuracy of tumor
      targeting and minimize toxicity to normal tissue. Targeted therapy in both breast
      and ovarian cancer has focused on antibodies, antibody drug conjugates (ADCs),
      and very recently the introduction of human antibody fusion proteins. Small
      molecule inhibitors and monoclonal antibodies (mAbs) are used in conjunction with
      chemotherapeutic drugs as a form of treatment but problems arise from a board
      expression of the target antigen in healthy tissues. Also, insufficient tumor
      penetration due to tight binding affinity and macromolecular size of mAbs
      compromise the efficacy of these ADCs. A more targeted approach is thus needed,
      and ADCs were designed to meet this need. However, in ADCs the method of
      conjugation of drug to antibody is >1, altering the structure of the drug which
      leads to off-target effects. Random conjugation also causes the drug to affect
      the pharmokinetics and biodistribution of the antibody and may cause nonspecific
      binding and internalization. Recombinant therapeutic proteins achieve controlled
      conjugation reactions and combine cytotoxicity and targeting in one molecule.
      They can also be engineered to extend half-life, stability and mechanism of
      action, and offer novel delivery routes. SNAP-tag fusion proteins are an example
      of a theranostic recombinant protein as they provide a unique antibody format to
      conjugate a variety of benzyl guanine modified labels, e.g. fluorophores and
      photosensitizers in a 1:1 stoichiometry. On the one hand, SNAP tag fusions can be
      used to optically image tumors when conjugated to a fluorophore, and on the other
      hand the recombinant proteins can induce necrosis/apoptosis in the tumor when
      conjugated to a photosensitizer upon exposure to a changeable wavelength of
      light. The dual nature of SNAP-tag fusions as both a diagnostic and therapeutic
      tool reinforces its significant role in cancer treatment in an era of precision
      medicine.

PMID- 29070976
TI  - Designing Human Antibodies by Phage Display.
AB  - With six approved products and more than 60 candidates in clinical testing, human
      monoclonal antibody discovery by phage display is well established as a robust
      and reliable source for the generation of therapeutic antibodies. While a vast
      diversity of library generation philosophies and selection strategies have been
      conceived, the power of molecular design offered by controlling the in vitro
      selection step is still to be recognized by a broader audience outside of the
      antibody engineering community. Here, we summarize some opportunities and
      achievements, e.g., the generation of antibodies which could not be generated
      otherwise, and the design of antibody properties by different panning strategies,
      including the adjustment of kinetic parameters.

PMID- 29070977
TI  - Antibody Isotypes for Tumor Immunotherapy.
AB  - Compared to the evolutionary diversity of antibody isotypes, the spectrum of
      currently approved therapeutic antibodies is biased to the human IgG1 isotype.
      Detailed studies into the different structures and functions of human isotypes
      have suggested that other isotypes than IgG1 may be advantageous for specific
      indications - depending on the complex interplay between the targeted antigen or
      epitope, the desired mode of action, the pharmacokinetic properties, and the
      biopharmaceutical considerations. Thus, it may be speculated that with the
      increasing number of antibodies becoming available against a broadening spectrum
      of target antigens, identification of the optimal antibody isotype for particular
      therapeutic applications may become critical for the therapeutic success of
      individual antibodies. Thus, investments into this rather unexplored area of
      antibody immunotherapy may provide opportunities for distinction in the
      increasingly busy 'antibody space'. Therefore, IgG, IgA, IgE as well as IgM
      isotypes will be discussed in this review.

PMID- 29070978
TI  - Modulating Cytotoxic Effector Functions by Fc Engineering to Improve Cancer
      Therapy.
AB  - In the last two decades, monoclonal antibodies have revolutionized the therapy of
      cancer patients. Although antibody therapy has continuously been improved, still
      a significant number of patients do not benefit from antibody therapy. Therefore,
      rational optimization of the antibody molecule by Fc engineering represents a
      major area of translational research to further improve this potent therapeutic
      option. Monoclonal antibodies are able to trigger a variety of effector
      mechanisms. Especially Fc-mediated effector functions such as antibody-dependent
      cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis
      (ADCP), and complement- dependent cytotoxicity (CDC) are considered important in
      antibody therapy of cancer. Novel mechanistic insights into the action of
      monoclonal antibodies allowed the development of various Fc engineering
      approaches to modulate antibodies' effector functions. Strategies in modifying
      the Fc glycosylation profile (Fc glyco-engineering) or approaches in engineering
      the protein backbone (Fc protein engineering) have been intensively evaluated. In
      the current review, Fc engineering strategies resulting in improved ADCC, ADCP
      and CDC activity are summarized and discussed.

PMID- 29070980
TI  - Components in Plasma-Derived Factor VIII, But Not in Recombinant Factor VIII
      Downregulate Anti-Inflammatory Surface Marker CD163 in Human Macrophages through
      Release of CXCL4 (Platelet Factor 4).
AB  - BACKGROUND: Hemarthrosis, or bleeding into the joints, is a hallmark of
      hemophilia. Heme triggers oxidative stress, inflammation, and destruction of
      cartilage and bone. The haptoglobin-CD163-heme oxygenase-1 (HO-1) pathway
      circumvents heme toxicity through enzymatic degradation of heme and transcription
      of antioxidant genes. Plasma-derived factor concentrates contain many proteins
      that might impact on cellular pathways in joints, blood, and vessels. METHODS:
      Activation of platelets from healthy volunteers was assessed by flow cytometry
      analysis of fibrinogen binding and CD62P expression. Platelet CXCL4 release was
      measured by ELISA. Human peripheral blood mononuclear cells were exposed to CXCL4
      or platelet supernatants (untreated or pre-stimulated with factor VIII (FVIII)
      products) during their differentiation to macrophages and analyzed for CD163
      expression. Some macrophage cultures were additionally incubated with autologous
      hemoglobin for 18 h for analysis of HO-1 expression. RESULTS: Platelet CXCL4
      release was increased by all 8 tested plasma-derived FVIII products but not the 3
      recombinant products. Macrophages exposed to supernatant from platelets treated
      with some plasma-derived FVIII products downregulated CD163 surface expression
      and failed to upregulate the athero- and joint protective enzyme HO-1 in response
      to hemoglobin. CONCLUSION: Plasma-derived FVIII products might promote bleeding
      induced joint injury via generation of macrophages that are unable to counteract
      redox stress.

PMID- 29070981
TI  - Red Cell Genotyping by Multiplex PCR Identifies Antigen-Matched Blood Units for
      Transfusion-Dependent Thai Patients.
AB  - BACKGROUND: Antigen-negative red cell transfusion is required for transfusion
      dependent patients. We developed multiplex PCR for red cell genotyping and
      calculated the possibility of finding compatible predicted phenotypes in Thai
      blood donor populations according to red cell alloantibodies found among Thai
      patients. METHODS: 600 DNA samples obtained from unrelated healthy central and
      northern Thai blood donors were tested with the newly developed multiplex PCR for
      FY*A, FY*B, JK*A, JK*B, RHCE*e, RHCE*E, DI*A and GYP*Hut, GYP*Mur, GYP*Hop,
      GYP*Bun, and GYP*HF allele detections. Additionally, the possibility of finding
      compatible predicted phenotypes in two Thai blood donor populations was
      calculated to estimate the minimal number of tests needed to provide compatible
      blood. RESULTS: The validity of multiplex PCR using known DNA controls and the
      phenotyping and genotyping results obtained by serological and PCR-SSP techniques
      were in agreement. The possibility of finding at least one compatible blood unit
      for patients with multiple antibodies was comparable in Thai populations.
      CONCLUSIONS: The multiplex PCR for red cell genotyping simultaneously interprets
      7 alleles and 1 hybrid GP group. Similar strategies can be applied in other
      populations depending on alloantibody frequencies in transfusion-dependent
      patients, especially in a country with limited resources.

PMID- 29070979
TI  - Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy.
AB  - Immunotherapy has the potential to support and expand the body's own
      armamentarium of immune effector functions, which have been circumvented during
      malignant transformation and establishment of cancer and is presently considered
      to be the most promising treatment option for cancer patients. Recombinant
      antibody technologies have led to a multitude of novel antibody formats, which
      are in clinical development and hold great promise for future therapies. Among
      these formats, bispecific antibodies are extremely versatile due to their high
      efficacy to recruit and activate anti-tumoral immune effector cells, their
      excellent safety profile, and the opportunity for use in combination with
      cellular therapies. This review article summarizes the latest developments in
      cancer immunotherapy using immuno-engagers for recruiting T cells and NK cells to
      the tumor site. In addition to antibody formats, malignant cell targets, and
      immune cell targets, opportunities for combination therapies, including check
      point inhibitors, cytokines and adoptive transfer of immune cells, will be
      summarized and discussed.

PMID- 29070982
TI  - Advanced Imaging for Precision Medicine in Breast Cancer: From Morphology to
      Function.

PMID- 29070983
TI  - Application of BI-RADS Descriptors in Contrast-Enhanced Dual-Energy Mammography:
      Comparison with MRI.
AB  - BACKGROUND: Contrast-enhanced (CE) magnetic resonance imaging (MRI) BI-RADS
      descriptors are used in the evaluation of contrast-enhanced dual-energy
      mammography (CEDEM) images of mass lesions and are assumed to be applicable.
      PATIENTS AND METHODS: Patients with suspicious mass lesions on mammography (BI
      RADS 4 or 5) were included. CEDEM examinations were performed using a modified
      prototype unit. CE-MRI was performed using a high temporal and high spatial
      resolution imaging protocol. 2 blinded breast radiologists evaluated all images
      using criteria related to contrast enhancement intensity and morphology according
      to the BI-RADS lexicon (5th edition) in 2 sessions. Histopathology was used as
      the standard of reference. RESULTS: 11 patients with 5 benign and 6 malignant
      index lesions were included. Enhancement characteristics were similar in the
      malignant cases. Enhancement of the benign lesions was moderate on CEDEM and
      strong on MRI. Discrepancies in the BI-RADS descriptors did not influence the
      final BI-RADS score. Overall, the BI-RADS assessment was almost identical in all
      cases. 1 malignant lesion was rated BI-RADS 4 with CEDEM and BI-RADS 5 with MRI,
      and 1 benign was rated BI-RADS 2 and BI-RADS 1, respectively. CONCLUSION: MRI BI
      RADS descriptors of contrast-enhancing lesions can be applied for the morphologic
      analysis of mass lesions on CEDEM.

PMID- 29070984
TI  - Added Value of Digital Breast Tomosynthesis Combined with Digital Mammography
      According to Reader Agreement: Changes in BI-RADS Rate and Follow-Up Management.
AB  - BACKGROUND: The aim of this study was to evaluate the added value of digital
      breast tomosynthesis (DBT) when combined with digital mammography (DM) in BI-RADS
      assessment and follow-up management. METHODS: From February 2014 to January 2015,
      214 patients underwent DM and DBT, acquired with a Siemens Mammomat Inspiration
      unit. 2 expert readers independently reviewed the studies in 2 steps: DM and
      DM+DBT, according to BI-RADS rate. Patients with BI-RADS 0, 3, 4, and 5 were
      recalled for work-up. Inter-reader agreement for BI-RADS rate and work-up rate
      were evaluated using Cohen's kappa. RESULTS: Inter-reader agreement (kappa value)
      for BI-RADS classification was 0.58 for DM and 0.8 for DM+DBT. DM+DBT increased
      the number of BI-RADS 1, 2, 4, 5 and reduced the number of BI-RADS 0 and 3 for
      both readers compared to DM alone. Regarding work-up rate agreement, kappa was
      poor for DM and substantial (0.7) for DM+DBT. DM+DBT also reduced the work-up
      rate for both Reader 1 and Reader 2. CONCLUSION: DM+DBT increased the number of
      negative and benign cases (BI-RADS 1 and 2) and suspicious and malignant cases
      (BI-RADS 4 and 5), while it reduced the number of BI-RADS 0 and 3. DM+DBT also
      improved inter-reader agreement and reduced the overall recall for additional
      imaging or short-interval follow-up.

PMID- 29070985
TI  - Dynamic Contrast-Enhanced Magnetic Resonance Imaging in the Assessment of
      Inflammatory Breast Cancer Prior to and After Neoadjuvant Treatment.
AB  - BACKGROUND: The aim of this study was to describe the dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) features of inflammatory breast cancer (IBC)
      and to assess the value of DCE-MRI for the prediction of pathological complete
      response (pCR). METHODS: Image analysis was performed in 15 patients with IBC
      (cT4d) and 12 patients with non-IBC (cT2), and included the assessment of BIRADS
      characteristics, skin alterations, enhancement characteristics, and changes post
      chemotherapy. Sensitivity and specificity of DCE-MRI for the presence of residual
      disease were obtained. Pearson's correlation coefficients were calculated
      comparing the (preoperative) tumor size with the histological size. RESULTS: Skin
      thickening/enhancement (80%) and non-mass-like enhancement (66.7%) occurred more
      often in IBC (16.7 vs. 8.3% in non-IBC). In 2 of 3 cases of IBC, pCR was
      correctly predicted (sensitivity 92%, specificity 67%), compared to 3 of 5 cases
      in non-IBC (sensitivity 86%, specificity 40%). Lower peak enhancement might be
      associated with a higher likelihood of pCR in IBC. No other parameters predicted
      eventual pCR. In IBC, no correlation between preoperative tumor size and
      histological size was found (r = 0.22, p = 0.50), whereas in non-IBC, size
      estimations were more accurate (r = 0.75, p = 0.03). CONCLUSION: IBC is
      characterized on MRI by skin changes and non-mass-like enhancement. Radiological
      complete response seems indicative of pCR in IBC and non-IBC. Size estimation of
      residual disease in IBC appears to be inaccurate.

PMID- 29070986
TI  - Automated Semi-Quantitative Analysis of Breast MRI: Potential Imaging Biomarker
      for the Prediction of Tissue Response to Neoadjuvant Chemotherapy.
AB  - BACKGROUND: We aimed to investigate an automated semi-quantitative software as an
      imaging biomarker for the prediction of tissue response (TR) after completion of
      neoadjuvant chemotherapy (NAC). METHODS: Breast magnetic resonance imaging (MRI)
      (1.5T, protocol according to international recommendations) of 67 patients with
      biopsy-proven invasive breast cancer were examined before and after NAC. After
      completion of NAC, histopathologic assessments of TR were classified according to
      the Chevallier grading system (CG1/4: full/non-responder; CG2/C3: partial
      responder). A commercially available fully automatic software (CADstream)
      extracted MRI parameters of tumor extension (tumor diameter/volume: TD/TV). Pre-
      versus post-NAC values were compared (DeltaTV and DeltaTD). Additionally, the
      software performed volumetric analyses of vascularization (VAV) after NAC.
      Accuracy of MRI parameters to predict TR were identified (cross-tabs, ROC, AUC,
      Kruskal-Wallis). RESULTS: There were 37 (34.3%) CG1, 7 (6.5%) CG2, 53 (49.1%)
      CG3, and 11 (10.2%) CG4 lesions. The software reached area under the curve levels
      of 79.5% (CG1/complete response: DeltaTD), 68.6% (CG2, CG3/partial response:
      VAV), and 88.8% to predict TR (CG4/non-response: DeltaTV). CONCLUSION: Semi
      quantitative automated analysis of breast MRI data enabled the prediction of
      tissue response to NAC.

PMID- 29070987
TI  - Results of Short-Term Follow-Up in BI-RADS 3 and 4a Breast Lesions with a
      Histological Diagnosis of Fibroadenoma at Percutaneous Needle Biopsy.
AB  - OBJECTIVE: To evaluate the usefulness of short-term (6 months) follow-up in
      patients with Breast Imaging Report and Data System (BI-RADS) 3 and 4a lesions,
      after a diagnosis of fibroadenoma at an image-guided biopsy. PATIENTS AND
      METHODS: The data of 318 women with 349 biopsy-proven fibroadenomas, a 6-month
      follow-up, and a follow-up of >= 24 months were retrospectively reviewed.
      Information on clinical history, lesion characteristics on ultrasound (US),
      mammography, and magnetic resonance imaging (MRI), BI-RADS classification, and
      follow-up was collected. The false-negative (FN) rate and the negative predictive
      value (NPV) for the biopsy were calculated. RESULTS: 43 patients (13.5%)
      presented with a palpable nodule; 18 (5.7%) had a history of breast cancer. There
      were 334 lesions visible on US (95.7%), 57 on US and mammography (16.3%), and 15
      on mammography only (4.3%); 37 lesions were first detected on MRI. All lesions
      were stable at 6 months. After an at least 1-year follow-up, 4 lesions changed
      their features and were excised. Histology showed 1 invasive lobular cancer, 1
      ductal carcinoma in situ, 1 phyllodes tumor, and 1 papilloma. The FN rate of the
      needle biopsy was 1.1% and the NPV was 98.9%. CONCLUSION: For lesions initially
      described as BI-RADS 3 and 4a with a histological diagnosis of fibroadenoma after
      biopsy, short-term follow-up can be avoided.

PMID- 29070988
TI  - Anti-Phosphohistone H3-Positive Mitoses Are Linked to Pathological Response in
      Neoadjuvantly Treated Breast Cancer.
AB  - BACKGROUND: We evaluated breast cancer (BC) core biopsies taken before
      neoadjuvant chemotherapy (NACT) by immunohistochemistry using anti-phosphohistone
      H3 (PHH3) antibody to determine mitosis, and correlated the results to
      clinicopathological data and histopathological regression of resected tumor
      specimens after NACT. METHODS: 72 patients with either triple-negative (TN) or
      luminal type BC received NACT with epirubicin/cyclophosphamide (EC) and
      Taxotere(r). Tumor regression was analyzed in resected specimens; pathological
      complete response (pCR) was achieved in 22.2%. Immunohistochemistry with PHH3 was
      performed on biopsy samples taken before treatment, and mitotic figures were
      evaluated in 10 high-power fields (HPF). RESULTS: PHH3-detected mitoses
      correlated significantly with tumor grading (p = 0.001). TNBC showed > 10 PHH3
      positive mitoses/10 HPF significantly more frequently than luminal type BC (p =
      0.003). Tumors with > 10 PHH3-positive mitoses/10 HPF achieved pCR significantly
      more often than those with <= 10 PHH3-positive mitoses/10 HPF (p = 0.031). Even
      luminal type BC with > 10 PHH3-positive mitoses/10 HPF was associated
      significantly with pCR compared to luminal type BC with <= 10 PHH3-positive
      mitoses/10 HPF (p = 0.016). CONCLUSION: NACT with EC and Taxotere is suitable for
      strong proliferating TNBC and luminal BC (> 10 PHH3-positive mitoses/10 HPF).
      Immunohistochemical determination of mitoses using anti-PHH3 antibody is a simple
      and robust method for predicting therapy response to NACT in BC tissue.

PMID- 29070989
TI  - Muscle-Sparing ADM-Assisted Breast Reconstruction Technique Using Complete Breast
      Implant Coverage: A Dual-Institute UK-Based Experience.
AB  - BACKGROUND: We report our early experience of a novel muscle-sparing breast
      (prepectoral) reconstruction technique using a pre-shaped Braxon(r) mesh
      (acellular dermal matrix) which completely wraps around the breast implant.
      METHODS: All patients who underwent prepectoral implant-based breast
      reconstruction between April 2014 and September 2015 were included in the
      analysis. The dermal matrix Braxon(r) used is a pre-shaped matrix which forms a
      complete implant mesh wrap. The new breast created is placed over the chest wall
      without disturbing the pectoralis musculature. RESULTS: A total of 51 (42
      unilateral and 9 bilateral) muscle-sparing breast reconstructions were carried
      out. Complications included implant loss (n = 1; 1.7%) secondary to wound
      infection, seroma (n = 4; 6.7%), and superficial wound dehiscence (n = 1; 1.7%)
      which was re-sutured without further complication. The median follow-up period
      was 16.4 (range 8-25) months. CONCLUSION: The early experience appears highly
      satisfactory with good clinical outcome. The novel prepectoral implant-based
      breast reconstruction using the mesh wrap provides an effective alternative to
      the more traditional submuscular implant-based technique.

PMID- 29070990
TI  - A Prospective Study to Evaluate the Effect of Paclitaxel on Cardiac Ejection
      Fraction.
AB  - BACKGROUND: The primary objective of the study was to evaluate the long-term
      changes in ejection fraction (EF) associated with paclitaxel infusion. METHODS:
      50 patients were enrolled in this prospective study between 2011 and 2015. The
      study design included frequent follow-up visits to the clinic, EF evaluation at
      baseline, and regular EF assessment by echocardiography for 30 months after
      treatment. RESULTS: The median baseline EF was 60% (95% confidence interval (CI)
      50-80%). At 30 months, the median EF was 48% (95% CI 40-60%; p = 0.03). During
      the 30-month follow-up, 10 (20%) patients developed grade 1 and 2
      cardiotoxicities; none developed grade 3 or 4 cardiotoxicities. Furthermore,
      paclitaxel cardiotoxicity increased among patients with high-risk features
      including associated diabetes mellitus, hypertension, prior radiotherapy to the
      chest wall, performance status of 2, and age > 60 years. CONCLUSION: Paclitaxel
      has cardiotoxic effects. Careful monitoring of cardiac function during and after
      paclitaxel infusion is required in patients with high-risk features.

PMID- 29070992
TI  - News from ASCO 2017.

PMID- 29070991
TI  - Magnetic Resonance Imaging after Breast Oncoplastic Surgery: An Update.
AB  - Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic
      outcome, is oncologically safe when applied to early-stage breast cancer. Breast
      cancer recurrence following conservative therapy may occur during the first 5
      years after treatment, with a peak incidence after 2 years. Therefore, during the
      follow-up period, patients undergo a series of ultrasound (US) and mammographic
      examinations. However, after surgery and radiation therapy, several modifications
      occur in the treated breast, causing difficulties in image interpretation,
      especially when local recurrence is suspected. Although not included in routine
      follow-up, magnetic resonance imaging (MRI) is often used in clinical practice,
      being considered more sensitive than the conventional imaging examinations in
      discriminating between postsurgical tissue modifications and tumor recurrence. In
      this review article, we analyze expected and pathologic breast MRI findings after
      conservative oncoplastic surgery compared to US and mammographic findings in
      order to distinguish local recurrence and avoid potential pitfalls in image
      interpretation.

PMID- 29070993
TI  - Different Response to Nivolumab in a Patient with Synchronous Double Primary
      Carcinomas of Hypopharyngeal Cancer and Non-Small-Cell Lung Cancer.
AB  - Nivolumab is a humanized IgG4 and programmed death 1 (PD-1) monoclonal antibody
      that has demonstrated antitumor efficacy in clinical trials of various malignant
      tumors including non-small-cell lung cancer and head and neck squamous cell
      carcinoma (SCC). However, patients with multiple primary malignancies were
      excluded in clinical trials. Thus, the efficacy of nivolumab in such patients has
      not been revealed yet. The programmed death ligand 1 (PD-L1) expression level is
      currently the main predictive biomarker of PD-1 inhibitors in various types of
      solid tumors and hematological malignancies. Here we describe a patient with
      synchronous double primary carcinomas of hypopharyngeal SCC and lung
      adenocarcinoma who exhibited different responses to nivolumab. After nivolumab
      treatment, hypopharyngeal SCC with moderate PD-L1 positivity by
      immunohistochemical staining showed a remarkable response; conversely, nivolumab
      was not effective against lung adenocarcinoma, which was negative for PD-L1. This
      suggests that tumors with different PD-L1 expressions may exhibit different
      responses to PD-1 inhibitors when multiple primary malignancies are present
      within one patient.

PMID- 29070994
TI  - Nivolumab-Induced Myocarditis Concomitant with Myasthenia Gravis.
AB  - We report a 69-year-old female patient with advanced lung cancer who developed
      myocarditis concomitant with myasthenia gravis (MG), also known as
      "Herzmyasthenie," after 3 cycles of nivolumab administration. Her initial
      symptoms were general malaise and double vision. However, her myocarditis
      deteriorated rapidly the following day, necessitating a temporary pacemaker and
      noninvasive positive pressure ventilation in the intensive care unit.
      Immunohistochemical examination of a myocardial biopsy suggested an immune
      response on the basis of HLA associations. The patient also developed impaired
      adduction of her left eye and elevated serum levels of acetylcholine receptor
      antibody, suggesting the onset of MG. Her condition gradually improved after
      immediate methylprednisolone pulse therapy. This case of nivolumab-induced
      "Herzmyasthenie" highlights the need to be aware that fulminant myocarditis might
      occur at the same time as MG during treatment with anti-programmed cell death-1
      monoclonal antibodies.

PMID- 29070995
TI  - Dramatic Response with Single-Agent Ibrutinib in Multiply Relapsed Marginal Zone
      Lymphoma with MYD88L265P Mutation.
AB  - The B-cell receptor signaling pathway is important in the lymphomagenesis of many
      lymphomas, including marginal zone lymphoma (MZL). Herein we describe a case of
      extranodal MZL refractory to multiple lines of therapy. The presence of an IgM
      paraprotein prompted further evaluation, and the patient was found to have an
      MYD88L265P mutation. Treatment with ibrutinib led to a dramatic response with
      prompt resolution of symptoms and significant improvement in measurable sites of
      disease. The excellent response to ibrutinib in our patient with MYD88L265P
      mutated refractory MZL supports a biological rationale for its use.

PMID- 29070996
TI  - Pancreatic Adenocarcinoma Masquerading as Idiopathic Chronic Pancreatitis with
      Delayed Diagnosis.
AB  - Pancreatic cancer carries poor prognosis. Establishing the diagnosis early could
      help in improving outcome. We are presenting a case of pancreatic cancer with
      delayed diagnosis. Our 60-year-old patient underwent multiple endoscopic
      ultrasound-guided biopsies with no evidence of malignancy. He had normal
      molecular tumor biomarkers. The patient needed 8 months to receive the diagnosis
      and initiate the treatment. There are no specific guidelines regarding choice of
      tissue sampling modalities in such cases.

PMID- 29070997
TI  - Recurrence of Ovarian Cancer with Placental Metastasis: A Case Report.
AB  - A 39-year-old primiparous Japanese female was admitted to the obstetrical
      emergency department of our hospital because of respiratory distress resulting
      from a large amount of pleural effusion, soon after a caesarean delivery (CD) at
      another hospital. While she was undergoing the CD, a giant ovarian tumour was
      identified. However, the tumour could not be removed at that facility and she was
      transferred to our hospital. Three days after the CD, a left salpingo
      oophorectomy was performed with the purpose of controlling pleural and peritoneal
      effusions. Based on her past treatment history and the information gathered from
      this surgery, recurrence of ovarian cancer was considered the final diagnosis.
      Earlier, at the age of 37 years, she had been diagnosed with stage IC ovarian
      adenocarcinoma arising from a mature cystic teratoma detected after a right
      salpingo-oophorectomy. These kinds of situations of accidental detection of
      recurrent advanced ovarian cancer in a newly pregnant patient in the emergency
      department are rare. Amongst them, we have identified an extremely rare case
      showing placental metastasis. The important lesson learnt from this case report
      is that detailed medical interviews and physical examinations are crucial when a
      pregnant woman visits a hospital without a letter of referral, especially in the
      third trimester of pregnancy.

PMID- 29070998
TI  - An Uncommon Presentation of a Metachronous Testicular Primary Nonseminoma and
      Seminoma Separated by Two Decades and a Testicular Cancer Literature Review.
AB  - INTRODUCTION: Testicular cancer is the most common malignancy in men aged 15-40
      years [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins,
      2011]. Its incidence comprises 0.8% of all male cancers worldwide, with a
      mortality rate of 0.1%. The incidence has nearly doubled from 1975 to 2007
      leading to the concern of environmental causes [Thomas: Am J Epidemiol 2013; 178:
      1240-1245]. Testicular cancer presents as a painless testicular mass without
      transillumination. Testicular cancer is subcategorized under germ cell testicular
      cancer or sex cord-stromal tumors. Of the germ cell tumors, approximately 90%
      originate in the testis, with the other 10% being extragonadal [Bols et al.:
      Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Typically, if
      a patient presents with a testicular mass and is 50 years old or older, the
      diagnosis of a primary lymphoma is considered until proven otherwise [Bols et
      al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Germ
      cell testicular cancer is further divided into the subtypes of seminomatous and
      nonseminomatous; each presents with a unique histology and differing treatment
      implications. DISCUSSION: Given the uniqueness of our patient's metachronous
      second testicular primary, we sought to compare our case findings to available
      historic publications. We sought to address the issues of the incidence of a
      second primary testicular malignancy with regard to varying histology, age of
      incidence, and timing of a second primary testicular cancer, the presence of
      bowel involvement, and finally a brief discussion of testosterone replacement
      therapy. CONCLUSION: A review of our case presents several unique factors. The
      above varying literature has shown our patient to have met the odds of a
      contralateral testicular primary development in that he had a nonseminomatous
      primary, followed by a second testicular primary seminoma. Our patient exceeded
      the 15-year cumulative risk of contralateral metachronous testicular cancer of
      1.9% versus the seemingly contradictory 5.2% cumulative risk 25 years after the
      first testicular germ cell tumor. With his second primary (seminoma), he
      presented with the common retroperitoneal landing zone site, though with an
      uncommon involvement of the gastrointestinal tract (<1%) and rare incidence of
      involving the duodenum.

PMID- 29070999
TI  - Treatment of Leptomeningeal Metastases in a Patient with Non-Small Cell Lung
      Cancer Harboring EGFR T790M Mutation.
AB  - BACKGROUND: Leptomeningeal metastasis (LM) is an uncommon complication in
      patients with solid tumors, associated with poor survival. However, LM appears to
      be more frequent in lung cancer patients with EGFR mutations, posing a unique
      clinical challenge to treating physicians. CASE PRESENTATION: We report the case
      of a 68-year-old Asian man with metastatic lung adenocarcinoma harboring an EGFR
      L858R mutation, which was initially treated with gefitinib. He developed disease
      progression 1 year later. Re-biopsy of the right lower lobe primary lesion
      revealed only an EGFR L858R mutation in the absence of a T790M mutation. The
      patient also experienced persistent confusion and generalized fatigue, and
      magnetic resonance imaging (MRI) of the brain demonstrated extensive LM. At this
      time, a liquid biopsy revealed an EGFR T790M mutation. Following initiation of
      treatment with osimertinib, the patient exhibited a rapid response with MRI of
      the brain showing substantial improvement of the LM after 6 months.
      Unfortunately, the LM recurred after 1 year at which time the patient declined
      further systemic chemotherapy. CONCLUSION: To our knowledge, this is the second
      reported case of LM in a patient with lung cancer harboring an EGFR T790M
      mutation that was successfully treated with osimertinib.

PMID- 29071000
TI  - Burned-Out Testicular Cancer: Really a Different History?
AB  - Two or more histological types characterize more than 60% of testicular germ cell
      tumors (GCTs). Burned-out testicular tumor refers to partial or complete
      histological regression of the primary testicular lesions. The most frequent GCT
      type involved in this kind of histological regression is choriocarcinoma,
      followed by embryonal carcinoma. To our knowledge, there are no cases of the
      burned-out phenomenon in teratoma. We report a case of a 19-year-old man
      presenting to our institute with a right testicular lesion, evidence of
      mediastinal and abdominal lymph node metastasis, and high levels of GCT serum
      biomarkers. After orchiectomy, the histopathological examination showed a mixed
      GCT: mature teratoma, immature teratoma, and histological features of testicular
      cancer regression (burned-out phenomenon). The patient underwent first-line
      chemotherapy (BEP regimen) which resulted in a complete instrumental and
      biochemical response after 4 cycles. Teratoma is considered a less aggressive
      type of GCT. In this particular case, metastatic disease seems to result from non
      germ cell components which underwent early spontaneous regression.

PMID- 29071001
TI  - Primary Hepatic Angiosarcoma: A Case Report with 10-Year Patient Medical Data.
AB  - In the current study, we report a case of a 46-year-old man who presented with
      sudden abdominal pain and was diagnosed with rupture of hepatic angiosarcoma
      (HAS). He underwent surgery, but died 13 days after the onset of the abdominal
      pain. Chronic exposure to carcinogens, such as thorium dioxide, arsenic, vinyl
      chloride, and radium, is associated with HAS. However, our patient had not been
      exposed to such carcinogens. He had submitted himself for annual medical checkups
      since he was employed. His liver was cirrhotic, and medical history data showed
      that he had had fatty liver for at least 10 years before HAS onset. Although
      liver cirrhosis may play a role in the occurrence of HAS, the connection of
      chronic fatty liver in the tumorigenesis remains unclear. Case reports regarding
      HAS with fatty liver are few. To the best of our knowledge, this is the first
      case of HAS occurring in a cirrhotic liver that advanced from persistent fatty
      stage. Given that HAS is a rare tumor, data collection is important for
      investigating its pathophysiology. Case presentations considering health
      conditions before HAS onset are limited; therefore, we present a case of HAS with
      annual health checkup data before disease onset.

PMID- 29071002
TI  - Liquid Biopsy Prevents Inaccurate Her2 Status Determination by in situ
      Hybridization in a Patient with Invasive Ductal Adenocarcinoma of the Breast:
      Case Report.
AB  - Utilization of circulating tumor DNA as a novel and noninvasive test for
      diagnosis confirmation, therapy selection, and cancer surveillance is a rapidly
      growing area of interest. In the wake of FDA approval of a liquid biopsy test, it
      is important for clinicians to acknowledge the obvious clinical utility of liquid
      biopsy for cancer management throughout the course of the disease. This case
      report describes a female with invasive ductal adenocarcinoma of the breast,
      where liquid biopsy was instrumental for her cancer characterization and
      personalized therapy selection.

PMID- 29071004
TI  - Older Adults Perceptions of Technology and Barriers to Interacting with Tablet
      Computers: A Focus Group Study.
AB  - BACKGROUND: New technologies provide opportunities for the delivery of broad,
      flexible interventions with older adults. Focus groups were conducted to: (1)
      understand older adults' familiarity with, and barriers to, interacting with new
      technologies and tablets; and (2) utilize user-engagement in refining an
      intervention protocol. METHODS: Eighteen older adults (65-76 years old; 83.3%
      female) who were novice tablet users participated in discussions about their
      perceptions of and barriers to interacting with tablets. We conducted three
      separate focus groups and used a generic qualitative design applying thematic
      analysis to analyse the data. The focus groups explored attitudes toward tablets
      and technology in general. We also explored the perceived advantages and
      disadvantages of using tablets, familiarity with, and barriers to interacting
      with tablets. In two of the focus groups, participants had previous computing
      experience (e.g., desktop), while in the other, participants had no previous
      computing experience. None of the participants had any previous experience with
      tablet computers. RESULTS: The themes that emerged were related to barriers
      (i.e., lack of instructions and guidance, lack of knowledge and confidence,
      health-related barriers, cost); disadvantages and concerns (i.e., too much and
      too complex technology, feelings of inadequacy, and comparison with younger
      generations, lack of social interaction and communication, negative features of
      tablets); advantages (i.e., positive features of tablets, accessing information,
      willingness to adopt technology); and skepticism about using tablets and
      technology in general. After brief exposure to tablets, participants emphasized
      the likelihood of using a tablet in the future. CONCLUSIONS: Our findings suggest
      that most of our participants were eager to adopt new technology and willing to
      learn using a tablet. However, they voiced apprehension about lack of, or lack of
      clarity in, instructions and support. Understanding older adults' perceptions of
      technology is important to assist with introducing it to this population and
      maximize the potential of technology to facilitate independent living.

PMID- 29071003
TI  - Successful Treatment of Cardiac Angiosarcoma Associated with Disseminated
      Intravascular Coagulation with Nab-Paclitaxel: A Case Report and Review of the
      Literature.
AB  - Angiosarcoma of the heart is an uncommon soft tissue sarcoma. A few cases of
      disseminated intravascular coagulation (DIC) associated with angiosarcoma
      occurring in various organs, but not the heart, have been reported. Although
      taxane is commonly used in the treatment of metastatic angiosarcoma, data on the
      efficacy of nab-paclitaxel for angiosarcoma are limited. Here, we report probably
      the first case of a patient with primary cardiac angiosarcoma with coexisting DIC
      who was successfully treated with nab-paclitaxel. A 62-year-old female with chief
      complaints of nausea and shortness of breath was diagnosed as having cardiac
      angiosarcoma with liver metastases. Four months after the resection of her
      primary tumor, the hepatic metastatic lesions progressed rapidly accompanied by
      new metastatic lesions in the right iliac bone and signs of DIC. She received nab
      paclitaxel as first-line chemotherapy. A response of stable disease was achieved
      after 2 treatment cycles and DIC was successfully controlled for at least 4
      months. This report suggests potential utility of nab-paclitaxel for angiosarcoma
      complicated with DIC. We also review the literature for all cases of angiosarcoma
      with DIC reported so far.

PMID- 29071005
TI  - Enhanced robust finite-time passivity for Markovian jumping discrete-time BAM
      neural networks with leakage delay.
AB  - This paper is concerned with the problem of enhanced results on robust finite
      time passivity for uncertain discrete-time Markovian jumping BAM delayed neural
      networks with leakage delay. By implementing a proper Lyapunov-Krasovskii
      functional candidate, the reciprocally convex combination method together with
      linear matrix inequality technique, several sufficient conditions are derived for
      varying the passivity of discrete-time BAM neural networks. An important feature
      presented in our paper is that we utilize the reciprocally convex combination
      lemma in the main section and the relevance of that lemma arises from the
      derivation of stability by using Jensen's inequality. Further, the zero
      inequalities help to propose the sufficient conditions for finite-time
      boundedness and passivity for uncertainties. Finally, the enhancement of the
      feasible region of the proposed criteria is shown via numerical examples with
      simulation to illustrate the applicability and usefulness of the proposed method.

PMID- 29071007
TI  - Gender Classification Based on Eye Movements: A Processing Effect During Passive
      Face Viewing.
AB  - Studies have revealed superior face recognition skills in females, partially due
      to their different eye movement strategies when encoding faces. In the current
      study, we utilized these slight but important differences and proposed a model
      that estimates the gender of the viewers and classifies them into two subgroups,
      males and females. An eye tracker recorded participant's eye movements while they
      viewed images of faces. Regions of interest (ROIs) were defined for each face.
      Results showed that the gender dissimilarity in eye movements was not due to
      differences in frequency of fixations in the ROI s per se. Instead, it was caused
      by dissimilarity in saccade paths between the ROIs. The difference enhanced when
      saccades were towards the eyes. Females showed significant increase in
      transitions from other ROI s to the eyes. Consequently, the extraction of
      temporal transient information of saccade paths through a transition probability
      matrix, similar to a first order Markov chain model, significantly improved the
      accuracy of the gender classification results.

PMID- 29071006
TI  - The emerging role of CCN6 in breast cancer invasion.
AB  - The CCN family of matricellular proteins is essential for cell communication and
      mediation of epithelial stromal cross-talks with roles in development and cancer.
      In particular, loss of CCN6 messenger RNA expression has been recognized in
      highly aggressive breast cancers, especially in inflammatory breast cancer and
      breast cancers with axillary lymph node metastasis. Recent findings can better
      explain the relevance of CCN6's reduced expression on human invasive breast
      carcinomas. CCN6 has been shown to play a role in the process of epithelial to
      mesenchymal transition (EMT), which converts epithelial cells into migratory
      mesenchymal-like cells with invasive abilities. Although the mechanism by which
      CCN6 promotes EMT and invasion has not been fully elucidated, current data
      suggest that it involves the recruitment of the transcriptional regulators Snai1
      and ZEB1 to the E-cadherin promoter.

PMID- 29071008
TI  - Selective Effects of Sport Expertise on the Stages of Mental Rotation Tasks With
      Object-Based and Egocentric Transformations.
AB  - It is well established that motor expertise is linked to superior mental rotation
      ability, but few studies have attempted to explain the factors that influence the
      stages of mental rotation in sport experts. Some authors have argued that
      athletes are faster in the perceptual and decision stages but not in the rotation
      stages of object-based transformations; however, stimuli related to sport have
      not been used to test mental rotation with egocentric transformations. Therefore,
      24 adolescent elite divers and 23 adolescent nonathletes completed mental
      rotation tasks with object-based and egocentric transformations. The results
      showed faster reaction times (RTs) for the motor experts in tasks with both types
      of transformations (object-based cube, object-based body, and egocentric body).
      Additionally, the differences in favour of motor experts in the perceptual and
      decision stages were confirmed. Interestingly, motor experts also outperformed
      nonathletes in the rotation stages in the egocentric transformations. These
      findings are discussed against the background of the effects of sport expertise
      on mental rotation.

PMID- 29071009
TI  - Hydrogen Electrooxidation in Ionic Liquids Catalyzed by the NTf2 Radical.
AB  - Hydrogen electrooxidation via a "hydrogen abstraction" mechanism in an aprotic
      ionic liquid 1-butyl-1-methylpyrrolidinium bis-(trifluoromethylsulfonyl)
      [Bmpy][NTf2] under anaerobic conditions was investigated using cyclic voltammetry
      and density functional theory (DFT). It is found that a platinum bound NTf2
      radical (NTf2*) formed by the oxidation of NTf2- at anodic potential can catalyze
      the oxidation of hydrogen and enhance its reaction rate. Both experimental and
      theoretical studies (DFT) have supported a mechanism involving a NTf2* radical
      intermediate that catalyzes the hydrogen redox processes.

PMID- 29071010
TI  - Error-Prone and Error-Free Translesion DNA Synthesis over Site-Specifically
      Created DNA Adducts of Aryl Hydrocarbons (3-Nitrobenzanthrone and 4
      Aminobiphenyl).
AB  - Aryl hydrocarbons such as 3-nitrobenzanthrone (NBA), 4-aminobiphenyl (ABP),
      acetylaminofluorene (AAF), benzo(a)pyrene (BaP), and 1-nitropyrene (NP) form
      bulky DNA adducts when absorbed by mammalian cells. These chemicals are
      metabolically activated to reactive forms in mammalian cells and preferentially
      get attached covalently to the N2 or C8 positions of guanine or the N6 position
      of adenine. The proportion of N2 and C8 guanine adducts in DNA differs among
      chemicals. Although these adducts block DNA replication, cells have a mechanism
      allowing to continue replication by bypassing these adducts: translesion DNA
      synthesis (TLS). TLS is performed by translesion DNA polymerases-Pol eta, kappa,
      iota, and zeta and Rev1-in an error-free or error-prone manner. Regarding the NBA
      adducts, namely, 2-(2'-deoxyguanosin-N2-yl)-3-aminobenzanthrone (dG-N2-ABA) and N
      (2'-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-ABA), dG-N2-ABA is produced
      more often than dG-C8-ABA, whereas dG-C8-ABA blocks DNA replication more strongly
      than dG-N2-ABA. dG-N2-ABA allows for a less error-prone bypass than dG-C8-ABA
      does. Pol eta and kappa are stronger contributors to TLS over dG-C8-ABA, and Pol
      kappa bypasses dG-C8-ABA in an error-prone manner. TLS efficiency and error
      proneness are affected by the sequences surrounding the adduct, as demonstrated
      in our previous study on an ABP adduct, N-(2'-deoxyguanosine-8-yl)-4
      aminobiphenyl (dG-C8-ABP). Elucidation of the general mechanisms determining
      efficiency, error-proneness, and the polymerases involved in TLS over various
      adducts is the next step in the research on TLS. These TLS studies will clarify
      the mechanisms underlying aryl hydrocarbon mutagenesis and carcinogenesis in more
      detail.

PMID- 29071012
TI  - Suppression of Primary Splenocyte Proliferation by Artemisia capillaris and Its
      Components.
AB  - The host immune system is the first line of host defense, consisting mainly of
      innate and adaptive immunity. Immunity must be maintained, orchestrated, and
      harmonized, since overactivation of immune responses can lead to inflammation and
      autoimmune diseases, while immune deficiency can lead to infectious diseases. We
      investigated the regulation of innate and adaptive immune cell activation by
      Artemisia capillaris and its components (ursolic acid, hyperoside, scopoletin,
      and scopolin). Macrophage phagocytic activity was determined using fluorescently
      labeled Escherichia coli, as an indicator of innate immune activation.
      Concanavalin A (ConA)- and lipopolysaccharide (LPS)-induced splenocyte
      proliferation was analyzed as surrogate markers for cellular and humoral adaptive
      immunity, respectively. Neither A. capillaris water extract (WAC) nor ethanol
      extract (EAC) greatly inhibited macrophage phagocytic activity. In contrast, WAC
      suppressed ConA- and LPS-induced proliferation of primary mouse splenocytes in a
      dose-dependent manner. Similarly, EAC inhibited ConA- and LPS-induced splenocyte
      proliferation. Oral administration of WAC in mice decreased ConA- and LPS-induced
      splenocyte proliferation, while that of EAC suppressed LPS-induced splenocyte
      proliferation. Repeated administration of WAC in mice inhibited ConA- and LPS
      induced splenocyte proliferation. Ursolic acid, scopoletin, and scopolin reduced
      ConA- and LPS-induced primary mouse splenocyte proliferation, while hyperoside
      did not show such activity. These results indicate that A. capillaris and its
      components, ursolic acid, scopoletin, and scopolin, suppress ConA- and LPS
      induced adaptive immune cell activation. The results suggest that A. capillaris
      is useful as a regulator of adaptive immunity for diseases involving excessive
      immune response activation.

PMID- 29071011
TI  - Cancer Chemopreventive Potential of Procyanidin.
AB  - Chemoprevention entails the use of synthetic agents or naturally occurring
      dietary phytochemicals to prevent cancer development and progression. One
      promising chemopreventive agent, procyanidin, is a naturally occurring polyphenol
      that exhibits beneficial health effects including anti-inflammatory,
      antiproliferative, and antitumor activities. Currently, many preclinical reports
      suggest procyanidin as a promising lead compound for cancer prevention and
      treatment. As a potential anticancer agent, procyanidin has been shown to inhibit
      the proliferation of various cancer cells in "in vitro and in vivo". Procyanidin
      has numerous targets, many of which are components of intracellular signaling
      pathways, including proinflammatory mediators, regulators of cell survival and
      apoptosis, and angiogenic and metastatic mediators, and modulates a set of
      upstream kinases, transcription factors, and their regulators. Although
      remarkable progress characterizing the molecular mechanisms and targets
      underlying the anticancer properties of procyanidin has been made in the past
      decade, the chemopreventive targets or biomarkers of procyanidin action have not
      been completely elucidated. This review focuses on the apoptosis and tumor
      inhibitory effects of procyanidin with respect to its bioavailability.

PMID- 29071013
TI  - Recommended Rice Intake Levels Based on Average Daily Dose and Urinary Excretion
      of Cadmium in a Cadmium-Contaminated Area of Northwestern Thailand.
AB  - This study was performed to investigate the dose-response relationship between
      average daily cadmium dose (ADCD) from rice and the occurrence of urinary cadmium
      (U-Cd) in individuals eating that rice. This was a retrospective cohort designed
      to compare populations from two areas with different levels of cadmium
      contamination. Five-hundred and sixty-seven participants aged 18 years or older
      were interviewed to estimate their rice intake, and were assessed for U-Cd. The
      sources of consumed rice were sampled for cadmium measurement, from which the
      ADCD was estimated. Binary logistic regression was used to examine the
      association between ADCD and U-Cd (cut-off point at 2 MUg/g creatinine), and a
      correlation between them was established. The lowest estimate was ADCD = 0.5
      MUg/kg bw/day [odds ratio (OR) = 1.71; with a 95% confidence interval (CI) 1.02
      2.87]. For comparison, the relationship in the contaminated area is expressed by
      ADCD = 0.7 MUg/kg bw/day, OR = 1.84; [95 % CI, 1.06-3.19], while no relationship
      was found in the non-contaminated area, meaning that the highest level at which
      this relationship does not exist is ADCD = 0.6 MUg/kg bw/day [95% CI, 0.99-2.95].
      Rice, as a main staple food, is the most likely source of dietary cadmium.
      Abstaining from or limiting rice consumption, therefore, will increase the
      likelihood of maintaining U-Cd within the normal range. As the recommended
      maximum ADCD is not to exceed 0.6 MUg/kg bw/day, the consumption of rice grown in
      cadmium-contaminated areas should not be more than 246.8 g/day. However, the
      exclusion of many edible plants grown in the contaminated area from the analysis
      might result in an estimated ADCD that does not reflect the true level of cadmium
      exposure among local people.

PMID- 29071014
TI  - Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone
      Therapy.
AB  - Thallium and its compounds are a class of highly toxic chemicals that cause wide
      ranging symptoms such as gastrointestinal disturbances; polyneuritis;
      encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and
      neurological toxicities; and have mutagenic and genotoxic effects. The present
      research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX)
      and deferiprone (L1) in reducing serum and tissue thallium levels after the
      administration of thallium (III), according to two different dosing regimens, to
      several groups of Wistar rats for 60 days. It was hypothesized that the two
      chelators might be more efficient as a combined therapy than as monotherapies in
      removing thallium (III) from the rats' organs. The chelators were administered
      orally as either single or combined therapies for a period of 14 days. Serum and
      tissue thallium (III) and iron concentrations were determined by flame atomic
      absorption spectroscopy. Serum and tissue thallium (III) levels were
      significantly reduced by combined therapy with DFX and L1. Additionally, iron
      concentrations returned to normal levels and symptoms of toxicity decreased.

PMID- 29071015
TI  - Comparative In Vitro Biological Toxicity of Four Kinds of Air Pollution
      Particles.
AB  - Accumulating epidemiological evidence indicates that exposure to fine air
      pollution particles (APPs) is associated with a variety of adverse health
      effects. However, the exact physiochemical properties and biological toxicities
      of fine APPs are still not well characterized. We collected four types of fine
      particle (FP) (diesel exhaust particles [DEPs], natural organic combustion [NOC]
      ash, synthetic organic combustion [SOC] ash, and yellow sand dust [YSD]) and
      investigated their physicochemical properties and in vitro biological toxicity.
      DEPs were almost entirely composed of ultrafine particles (UFPs), while the NOC,
      SOC, and YSD particles were a mixture of UFPs and FPs. The main elements in the
      DEPs, NOC ash, SOC ash, and YSD were black carbon, silicon, black carbon, and
      silicon, respectively. DEPs exhibited dose-dependent mutagenicity even at a low
      dose in Salmonella typhimurium TA 98 and 100 strains in an Ames test for
      genotoxicity. However, NOC, SOC, and YSD particles did not show any mutagenicity
      at high doses. The neutral red uptake assay to test cell viability revealed that
      DEPs showed dose-dependent potent cytotoxicity even at a low concentration. The
      toxicity of DEPs was relatively higher than that of NOC, SOC, and YSD particles.
      Therefore, these results indicate that among the four FPs, DEPs showed the
      highest in vitro biological toxicity. Additional comprehensive research studies
      such as chemical analysis and in vivo acute and chronic inhalation toxicity tests
      are necessary to determine and clarify the effects of this air contaminant on
      human health.

PMID- 29071016
TI  - Environmental Exposure of Sperm Sex-Chromosomes: A Gender Selection Technique.
AB  - Preconceptual sex selection is still a highly debatable process whereby X- and Y
      chromosome-bearing spermatozoa are isolated prior to fertilization of the oocyte.
      Although various separation techniques are available, none can guarantee 100%
      accuracy. The aim of this study was to separate X- and Y-chromosome-bearing
      spermatozoa using methods based on the viability difference between the X- and Y
      chromosome-bearing spermatozoa. A total of 18 experimental semen samples were
      used, written consent was obtained from all donors and results were analysed in a
      blinded fashion. Spermatozoa were exposed to different pH values (5.5, 6.5, 7.5,
      8.5, and 9.5), increased temperatures (37 degrees C, 41 degrees C, and 45 degrees
      C) and ROS level (50 MUM, 750 MUM, and 1,000 MUM). The live and dead cell
      separation was done through a modified swim-up technique. Changes in the sex
      chromosome ratio of samples were established by double-label fluorescent in situ
      hybridization (FISH) before and after processing. The results indicated
      successful enrichment of Xchromosome-bearing spermatozoa upon incubation in
      acidic media, increased temperatures, and elevated H2O2. This study demonstrated
      the potential role for exploring the physiological differences between X-and Y
      chromosome-bearing spermatozoa in the development of preconceptual gender
      selection.

PMID- 29071017
TI  - Anti-Inflammatory Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde, a Component of
      Polysiphonia morrowii, In Vivo and In Vitro.
AB  - 3-Bromo-4,5-dihydroxybenzaldehyde (BDB) is a natural bromophenol compound that is
      most commonly isolated from red algae. The present study was designed to
      investigate the anti-inflammatory properties of BDB on atopic dermatitis (AD) in
      mice induced by 2,4-dinitrochlorobenzene (DNCB) and on lipopolysaccharide (LPS)
      stimulated murine macrophages. BDB treatment (100 mg/kg) resulted in suppression
      of the development of AD symptoms compared with the control treatment (induction
      only), as demonstrated by reduced immunoglobulin E levels in serum, smaller lymph
      nodes with reduced thickness and length, a decrease in ear edema, and reduced
      levels of inflammatory cell infiltration in the ears. In RAW 264.7 murine
      macrophages, BDB (12.5, 25, 50, and 100 MUM) suppressed the production of
      interleukin-6, a proinflammatory cytokine, in a dose-dependent manner. BDB also
      had an inhibitory effect on the phosphorylation of nuclear factor kappa-light
      chain-enhancer of activated B cells (NF-kappaB) and signal transducer and
      activator of transcription 1 (STAT1; Tyr 701), two major signaling molecules
      involved in cellular inflammation. Taken together, the results show that BDB
      treatment alleviates inflammatory responses in an atopic dermatitis mouse model
      and RAW 264.7 macrophages. These results suggest that BDB may be a useful
      therapeutic strategy for treating conditions involving allergic inflammation such
      as atopic dermatitis.

PMID- 29071018
TI  - A 90-Day Inhalation Toxicity Study of Ethyl Formate in Rats.
AB  - Ethyl formate, a volatile solvent, has insecticidal and fungicidal properties and
      is suggested as a potential fumigant for stored crop and fruit. Its primary
      contact route is through the respiratory tract; however, reliable repeated
      toxicological studies focusing on the inhalation route have not been published to
      date. Therefore, the present study was conducted to investigate the safety of a
      90-day repeated inhalation exposure in rats. Forty male and 40 female rats were
      exposed to ethyl formate vapor via inhalation at concentrations of 0, 66, 330,
      and 1,320 ppm for 6 hr/day, 5 days a week for 13 weeks. Clinical signs, body
      weights, food consumption, urinalysis, hematologic parameters, serum chemistry
      measurements, organ weights, necropsy, and histopathological findings were
      compared between the control and ethyl formate-exposed groups. Locomotor activity
      decreased during exposure and recovered afterward in male and female rats exposed
      to 1,320 ppm ethyl formate. Body weight and food consumption continuously
      decreased in both sexes exposed to 1,320 ppm ethyl formate from week 1 or 3
      compared with the control values. The increases in adrenal weight and decreases
      in thymus weight were noted in both sexes exposed to ethyl formate at 1,320 ppm.
      Degeneration, squamous metaplasia of olfactory epithelium in the nasopharyngeal
      tissue, or both were noted in the male and female rats at 1,320 ppm and female
      rats at 330 ppm ethyl formate. Taken together, our results indicate that ethyl
      formate-induced changes were not observed in male and female rats at 330 and 66
      ppm, respectively. This indicates that exposure to ethyl formate at
      concentrations below 66 ppm for 90 days is relatively safe in rats. This is the
      first report of a full-scale repeated inhalation toxicity assessment in rats and
      could contribute to controlling occupational environmental hazards related to
      ethyl formate.

PMID- 29071019
TI  - Lamivudine Therapy Exacerbates Bilirubinemia in Patients Underlying Severely
      Advanced Hepatitis.
AB  - Lamivudine belongs to the set of antiviral agents effective against hepatitis B
      virus infection. Given case reports on liver injuries after certain antiviral
      agent treatments, this study examined the effects of lamivudine on alanine
      aminotransferase (ALT) and total bilirubin (TB) using a medical system database.
      A total of 1,321 patients taking lamivudine alone or with others were evaluated
      using laboratory hits in an electronic medical system at Seoul National
      University Hospital from 2005 through 2011. The patients were grouped according
      to prior ALT results: G#1, ALT < 40 IU/L; G#2, 40 IU/L <= ALT < 120 IU/L; G#3,
      120 IU/L <= ALT < 240 IU/L; and G#4, ALT >= 240 IU/L. In G#1 and G#2 patients,
      lamivudine or adefovir treatment decreased ALT and TB compared to prior values.
      In G#3 and G#4 patients with three times the upper limit of normal (ULN) <= ALT <
      15 times the ULN, both ALT and TB were decreased after treatment with lamivudine
      alone, or adefovir following lamivudine therapy, indicating that lamivudine
      therapy ameliorated liver functions. However, in G#4 patients who experienced
      severely advanced hepatitis (ALT >= 15 times the ULN, or >= 600 IU/L), lamivudine
      augmented TBmax (6.3->13.3 mg/dL) despite a slight improvement in ALT (839->783
      IU/L), indicative of exacerbation of bilirubinemia. Patients who used adefovir
      after lamivudine also showed a high incidence of hyperbilirubinemia when they
      experienced severely advanced hepatitis. Treatment with adefovir alone did not
      show the effect. In conclusion, lamivudine may increase the risk of
      hyperbilirubinemia in patients with severely advanced hepatitis, implying that
      caution should be exercised when using lamivudine therapy in certain patient
      populations.

PMID- 29071020
TI  - In Vitro Comparison Of Fluoride Gel Alone and in Combination With Er,Cr:YSGG
      Laser on Reducing White Spot Lesions in Primary Teeth.
AB  - Introduction: Laser therapy has been suggested as a method for caries-prevention,
      and ErCr:YSGG laser is increasingly used in dentistry. This study aimed to
      compare the efficacy of fluoride gel alone and in conjunction with Er,Cr:YSGG
      laser for remineralization of white spot lesions (WSLs) in primary teeth.
      Methods: This study was conducted on 20 primary teeth with WSLs extracted for
      orthodontic reasons. Three sections were made of each tooth at the site of WSLs.
      The surface area of WSLs was measured under a stereomicroscope at *25
      magnification. Samples were assigned to 3 groups of control (group 1), exposure
      to 1.23% APF gel for 4 minutes (group 2) and Er,Cr:YSGG laser (0.5 W power, 20 Hz
      frequency, 60% water, 40% air, pulse duration of 5+/-1 seconds) plus fluoride
      (group 3). All samples were stored in artificial saliva for 10 days and then the
      surface area of the WSLs was measured again under a stereomicroscope. Data were
      analyzed using the Kruskal-Wallis, MannWhitney and Wilcoxon signed rank tests.
      Results: The reduction in surface area of the WSLs was significantly different
      between the control and fluoride (P<0.001) and also the control and laser plus
      fluoride groups (P<0.001); the difference between fluoride and laser plus
      fluoride groups was not significant (P=0.265). Comparison of the surface area of
      WSLs before and after the intervention showed no significant difference in group
      one (P=0.737) while this difference in groups 2 (P<0.001) and 3 (P<0.001) was
      statistically significant. Conclusion: The results showed that Er,Cr:YSGG laser
      irradiation plus 1.23% APF gel was not significantly different from the
      application of fluoride gel alone in enhancing the remineralization of WSLs.

PMID- 29071021
TI  - The Effect of Er:YAG Laser on Entroccocus faecalis Bacterium in the Pulpectomy of
      Anterior Primary Teeth.
AB  - Introduction: Successful root canal therapy depends on the complete elimination
      of microorganisms such as Entroccocus faecalis, which is impossible to achieve
      with the traditional methods. Lasers are recently introduced as a new method to
      solve the problem. The present study is planned and performed to examining the
      antibacterial effect of Er: YAG laser. Methods: Sixty extracted anterior primary
      teeth were prepared and sterilized. E. faecalis bacterium was cultured in canals.
      Samples were randomly divided into two groups. The first group was disinfected by
      NaOCl 5/25% and Er: YAG laser and the second group just by NaOCl 5/25%. Samples
      of canal contents were cultured and colony counts were calculated. The results
      were analyzed statistically by SPSS software and Mann Whitney test. Results:
      There was no significant difference between colony counts in both groups
      (P=0.142). But the number of colonies in the first group was lower than in the
      second group. Conclusion: Although, Er: YAG laser cannot completely eliminate E.
      faecalis bacterium, its simultaneous use with NaOCl decreases E. faecalis.

PMID- 29071022
TI  - In Vitro Comparison of Diagnostic Accuracy of DIAGNOdent and Digital Radiography
      for Detection of Secondary Proximal Caries Adjacent to Composite Restorations.
AB  - Introduction: Early detection of secondary proximal caries is critical for the
      preservation of tooth vitality. This study sought to assess and compare the
      diagnostic accuracy of DIAGNOdent and digital radiography for detection of
      secondary proximal caries adjacent to composite restorations. Methods: Sixty
      extracted molars including 30 teeth with carious lesions and 30 sound teeth were
      randomly selected. Class II cavities were prepared in all teeth and carious
      dentin was intentionally left in the gingival floor of cavities in 30 carious
      teeth. All cavities were restored with composite resin. The teeth were mounted in
      wax blocks (three teeth per block) and examined for caries using (DIAGNOdent kaVo
      Dental, Biberach, Germany). Digital radiographs using DIGORA photostimulable
      phosphor (PSP) plates (Soredex Corporation, Helsinki, Finland) were obtained from
      all teeth using the parallel technique and were evaluated by 4 observers.
      Repeated measure analysis of variance (ANOVA) was applied to calculate
      sensitivity and specificity values of the two diagnostic techniques. Receiver
      operating characteristic (ROC) curve was plotted for DIAGNOdent results and based
      on that, the cutoff points were determined. Results: The sensitivity and
      specificity values at the cut-off point of 10.5 were 0.622+/-0.038 and 0.822+/
      0.077 for DIAGNOdent and 0.591+/-0.093 and 0.891+/-0.083 for digital radiography,
      respectively. The area under the ROC curve was 0.7 for DIAGNOdent. Weighted kappa
      revealed moderate to almost perfect intra-observer agreement (0.46-0.99).
      Intraclass correlation coefficient (ICC) for DIAGNOdent was calculated to be
      0.88. Conclusion: No statistically significant difference was noted in diagnostic
      accuracy of DIAGNOdent and digital radiography for detection of secondary
      proximal caries adjacent to composite restorations. Thus, DIAGNOdent may be used
      as an adjunct diagnostic tool for detection of secondary proximal caries beneath
      composite restorations.

PMID- 29071023
TI  - The Effect of Low Level Laser Therapy on Pemphigus Vulgaris Lesions: A Pilot
      Study.
AB  - Introduction: Pemphigus vulgaris is a chronic blistering skin disease. Management
      of recalcitrant pemphigus ulcers is a great problem. Low Level Laser Therapy
      (LLLT) is known to supply direct biostimulative light energy to body cells. This
      study evaluates the efficacy of low power laser in the healing of pemphigus
      lesions. Methods: Ten patients with pemphigus vulgaris were enrolled in the
      trial. The LED-LLLT system used was the Thor LED clusters (109, 69 or 19 diode)
      (England) with 660 nm wavelength in continuous wave (CW) and 30 mW energy. Both
      sides of the patients' lesion were photographed prior to the study and in each
      laser therapy session. Results: The pattern of changes in qualitative wound score
      (QWS) patterns differed significantly over time between the two therapies
      (treatment * time interactions, P<0.0001). When compared to the routine therapy,
      the laser therapy showed more decrease in mean QWS in all sessions in comparison
      with baseline. Conclusion: Application of low level laser simultaneously with
      conventional therapy could result in sensational healing of ulcers especially in
      patients who do not respond to conventional treatment or suffering from
      recalcitrant lesions.

PMID- 29071024
TI  - Fracture Resistance of Incisal Fragments Following Reattachment With Different
      Techniques in Simulated Crown Fractures.
AB  - Introduction: The aim of the present study was to evaluate and compare the effect
      of acidetching and Er, Cr:YSGG laser treatment before the reattachment of incisal
      fragments in coronal fractures of permanent incisor teeth. Methods: Sixty-six
      sound human maxillary incisors were randomly divided into 3 groups (n=22). Teeth
      were embedded in self-cure acrylic resins by leaving one-third of the crowns out,
      and uncomplicated crown fractures were obtained using an Instron testing device.
      The fragments were reattached using 3 different procedures and a hybrid resin
      composite (Z250): Group I: Acid etching + Prime & Bond NT; Group II: Er,Cr:YSGG +
      Prime & Bond NT; Group III: Er,Cr:YSGG + Acid etching + Prime & Bond NT. The
      percentages of shear bond strengths were determined by comparing fracture
      strengths of sound and reattached teeth for 3 groups. All data were analyzed
      statistically with Kruskal-Wallis H test. Results: Mean fracture strengths of the
      reattached fragments were between 51.02% and 62.93% of that of the sound teeth in
      all groups. Group I had significantly higher percentages of shear bond strength
      values (P<0.05) when compared to group II and group III. No significant
      difference (P>0.05) was found between group II and group III. Conclusion: The
      findings of the present study show that Er,Cr:YSGG laser irradiation prior to the
      reattachment of incisal fragments has a negative effect on fracture strength.

PMID- 29071025
TI  - Effect of Various Laser Surface Treatments on Repair Shear Bond Strength of Aged
      Silorane-Based Composite.
AB  - Introduction: Successful repair of composite restorations depends on a strong
      bond between the old composite and the repair composite. This study sought to
      assess the repair shear bond strength of aged silorane-based composite following
      surface treatment with Nd:YAG, Er,Cr:YSGG and CO2 lasers. Methods: Seventy-six
      Filtek silorane composite cylinders were fabricated and aged by 2 months of water
      storage at 37 degrees C. The samples were randomly divided into 4 groups (n=19)
      of no surface treatment (group 1) and surface treatment with Er,Cr:YSGG (group
      2), Nd:YAG (group 3) and CO2 (group 4) lasers. The repair composite was applied
      and the shear bond strength was measured. The data were analyzed using one-way
      analysis of variance (ANOVA) and Tukey posthoc test. Prior to the application of
      the repair composite, 2 samples were randomly selected from each group and
      topographic changes on their surfaces following laser irradiation were studied
      using a scanning electron microscope (SEM). Seventeen other samples were also
      fabricated for assessment of cohesive strength of composite. Results: The highest
      and the lowest mean bond strength values were 8.99 MPa and 6.69 MPa for
      Er,Cr:YSGG and control groups, respectively. The difference in the repair bond
      strength was statistically significant between the Er,Cr:YSGG and other groups.
      Bond strength of the control, Nd:YAG and CO2 groups was not significantly
      different. The SEM micrographs revealed variable degrees of ablation and surface
      roughness in laser-treated groups. Conclusion: Surface treatment with Er,Cr:YSGG
      laser significantly increase the repair bond strength of aged silorane-based
      composite resin.

PMID- 29071026
TI  - In Vitro Effect of Bleaching With 810 nm and 980 nm Diode Laser on Microhardness
      of Self-cure and Light-Cure Glass Ionomer Cements.
AB  - Introduction: This study sought to assess the effect of bleaching combined with
      irradiation of 810 nm and 980 nm diode laser on microhardness of 2 commonly used
      self-cure and light-cure glass ionomer cements (GICs) in comparison with
      conventional bleaching (without laser). Methods: In this in vitro, experimental
      study, 60 samples were fabricated of A2 shade of Fuji IX and Fuji II LC GICs
      (n=30) and each group was divided into 3 subgroups (n=10). The first subgroups
      were subjected to bleaching with Opalescence Xtra Boost plus 980 nm diode laser
      irradiation. The second subgroups were subjected to bleaching with Opalescence
      Boost plus 810 nm diode laser irradiation and the third subgroups were subjected
      to bleaching with Opalescence Xtra Boost without laser. Microhardness was
      measured at baseline and after the intervention using Vickers hardness tester.
      The data were analyzed using two-way analysis of variance (ANOVA) (P<0.05).
      Results: Microhardness decreased in all subgroups after the intervention
      (P<0.001) irrespective of the type of GIC (P=0.201) or surface treatment
      (P=0.570). The baseline microhardness of the three subgroups within each group of
      GIC was not significantly different (P=0.456), but the baseline microhardness of
      conventional GIC was significantly higher than that of resin modified GIC
      (P=0.004). Conclusion: Bleaching with/without laser irradiation decreases the
      microhardness of GICs. The baseline microhardness of conventional GIC is higher
      than that of resin modified GIC.

PMID- 29071027
TI  - Antibacterial Effect of Diode Laser in Pulpectomy of Primary Teeth.
AB  - Introduction: Laser irradiation has been suggested as an adjunct to traditional
      methods of canal preparation but few studies are available on the antibacterial
      effect of diode laser in pulpectomy of primary teeth. The purpose of the present
      study is to investigate the antibacterial effect of diode laser in pulpectomy of
      primary teeth, in addition to define the optimal and harmless diode lasing
      conditions in the root canal. Methods: A total of 125 single rooted primary teeth
      were selected. After traditional canal cleaning, they were divided in 2 groups.
      Sixty-five specimens after culturing of Enterococcus faecalis into the canals,
      were divided in 3 groups: (1) traditional canal cleaning with 0.5% NaOCl
      irrigation, (2) method of group 1+ 1.5 W diode laser (980 nm, pulse), (3) without
      treatment (5 specimens). Then the specimens were cultured and after colony
      counting under light microscope, were statistically analyzed by Kruskal-Wallis
      and Mann-Whitney tests. For 60 specimens, temperature rise of apical and cervical
      parts of the external root surface were measured using 2 thermocouple type K,
      when radiating a 1.5 W diode laser into the canal. Results: In the first
      experiment, the diode laser group showed tmost reduction in bacterial count. And
      in the second experiment, the mean temperature rise of external root surface was
      less than the threshold of periodontal ligament (PDL) damage. Conclusion: Diode
      laser with a power output of 1.5 W, is effective in reduction of E. faecalis
      bacterial count without damaging periodontal structures.

PMID- 29071028
TI  - Successful Use of Lower-Level Laser Therapy in the Treatment of Medication
      Related Osteonecrosis of the Jaw.
AB  - Case Presentation: This study aimed to report a case of medication related
      osteonecrosis of the jaw (MRONJ) of a 65-year-old female patient referred to the
      Oral and Maxillofacial Surgery team from Aracatuba Dental School, complaining
      about mobility of a previously dental implant placed on the posterior maxillary
      region. Clinical examination revealed an extensive necrosis area around the
      implant region. The patient reported bisphosphonate therapy with sodium
      alendronate for prevention of osteoporosis 5 years ago. A diagnosis of MRONJ was
      reached and the treatment decided was to remove the dental implant damaged and
      use the lower-level laser therapy (LLLT) associated with antibiotic therapy with
      clindamycin 300 mg and mouth rinses with chlorhexidine 0.12%. Conclusion: Six
      months after the treatment with LLLT a complete healing of the affected area was
      observed and 12 months after treatment the patient was rehabilitated with fixed
      dental prosthesis and showed excellent tissue healing of the necrosis areas. It
      was concluded that the use of LLLT showed to be a good option in the treatment of
      MRONJ.

PMID- 29071029
TI  - Safety and Effectiveness of Low-Level Laser Therapy in Patients With Knee
      Osteoarthritis: A Systematic Review and Meta-analysis.
AB  - Introduction: Low-level laser therapy (LLLT) was introduced as an alternative non
      invasive treatment for osteoarthritis, but its effectiveness is still
      controversial. The main objective of this article was to determine the safety and
      efficacy of LLLT in patients with knee osteoarthritis (KOA). Methods: In order to
      gather evidence, main medical databases as well as relevant websites were browsed
      without time limit. We searched with appropriate keywords and strategies. After
      quality assessment of studies, study data were extracted by two reviewers.
      Standard mean difference proposed through inverse variance was used in the meta
      analysis using the random-effects model. Twelve values were used for the
      evaluation of heterogeneity. Results: A total of 823 studies, 14 randomized
      controlled trials (RCTs) were selected after final review. There was a
      significant difference between LLLT and placebo in pain at rest (P=0.02), pain at
      activity (P=0.01), total pain (P=0.03), WOMAC function (P=0.01), WOMAC stiffness
      (P=0.02) and WOMAC total (P<0.0001) in favor of the LLLT. There was no
      significant difference between LLLT and Placebo in WOMAC pain (P=0.09) and range
      of motion (P=0.1). Conclusion: In spite of some positive findings, this meta
      analysis lacked data on how LLLT effectiveness is affected with important
      factors: wavelength, energy density, treatment duration, numbers of sessions the
      treatment, severity of KOA and site of application.

PMID- 29071031
TI  - The Effect of Combination of Red, Infrared and Blue Wavelengths of Low-Level
      Laser on Reduction of Abdominal Girth: A Before-After Case Series.
AB  - Introduction: The objective of this study was to assess the efficacy of a
      combination of 3 wavelengths (including red, infra-red, and blue) of low-level
      laser (LLL) as a non-invasive therapeutic method to reduce abdominal girth. To
      achieve biochemical activity on adipocytes, a red laser was used in our selective
      laser combination. Near-infrared laser was used to increase depth of penetration.
      Nitrosyl complexes of hemoglobin (NO-Hb) are sensitive to blue light, thereby
      leading to increase in release of biologically active nitric oxide (NO), which
      can affect tissue perfusion. Thus, a blue LED was added to the laser combination.
      Methods: Eighteen females participated in the study. Twelve sessions of laser
      therapy were performed, 2 sessions per week for each subject. Continuous wave
      diode lasers, including red (630 nm), infra-red (808 nm), and a blue LED (450 nm)
      were applied and were all designed by the Canadian Optic and Laser Center.
      Results: Statistical analyses revealed that upper abdomen size significantly
      decreased from pre- (91.86 +/- 11.16) to post- (87.41 +/- 10.52) low-level laser
      therapy (LLLT) (P<0.001). Middle abdomen size showed significant reduction from
      pre- (97.02 +/- 8.82) to post- (91.97 +/- 8.49) LLLT (P<0.001). Lower abdomen
      size significantly decreased from pre- (100.36 +/- 9.45) to post- (95.80 +/-
      8.52) LLLT (P<0.001). Conclusion: Based on this case series pilot investigation,
      the combination of 3 different wavelengths of LLL was effective for abdominal
      girth reduction in 100% of our subjects (P<0.001), without any side effects.
      Future studies will assess the long-term benefits of this laser combination for
      reduction of subcutaneous fat deposits.

PMID- 29071030
TI  - Diabetic Retinopathy and Laser Therapy in Rats: A Protein-Protein Interaction
      Network Analysis.
AB  - : Introduction: Diabetic retinopathy (DR) is a serious microvascular complication
      of diabetes which can cause vision loss or blindness ultimately. Non enzymatic
      glycation of proteins leads to advanced glycation end products (AGEs) in DR.
      Since laser therapy is a well-established method, in this study, protein-protein
      interaction (PPI) network is applied for protein targets in DR disease in rats
      treated by laser. Methods: In this study, we focused on articles that
      investigated and compared the proteome profiles of DR rats with healthy control
      and also DR rats before and after laser therapy. The networks of related
      differentially expressed proteins were explored using Cytoscape version 3.3.0,
      the PPI analysis methods and ClueGO. Results: Analysis of PPI network of 37
      related proteins to DR rats including 108 nodes, introduced 10 hub-bottleneck
      proteins and 5 concerned biochemical pathways. On the other hand, PPI analysis of
      related proteins to DR rats before and after laser therapy corresponded to 33
      proteins and 2 biological pathways. Discussion: Centrality and cluster screening
      identified hub-bottelneck genes, including Aldoa, HSPD1, Pgam2, Mapk3, SLC2A4,
      Ctnnb1, Ywhab, HSPA8, GAPDH and Actb for DR rats versus healthy control and ENO1,
      Aldoa, GAPDH for DR samples after laser therapy. CONCLUSION: Gene expression
      analysis of the DR samples treated via laser therapy provides a molecular
      evidence in support of the therapeutic effect of laser.

PMID- 29071032
TI  - Comparative effectiveness of Low Level Laser therapy and Transcutaneous Electric
      Nerve Stimulation on Temporomandibular Joint Disorders.
AB  - Introduction: Temporomandibular joint disorders (TMDs) are the most common source
      of pain on the face. There are multiple etiologies, and several types of
      treatment have been reported. The use of non-invasive and reversible therapies in
      the treatment of such problems is recommended. The present study evaluated the
      effect of low-level laser (LLL) therapy and transcutaneous electric nerve
      stimulation (TENS) on TMDs. Methods: In this single-blind study, 40 patients with
      temporomandibular disorders were randomly divided into four groups: TENS (TENSTem
      dental), LLL (diode 810 nm CW), shamTENS, and sham-LLL. All subjects were
      examined and data on pain and tenderness in the temporomandibular joint (TMJ) and
      masticatory muscles (using the visual analogue scale) and mouth-opening (distance
      between incisal edges before feeling pain; mm) were collected before baseline
      (T1), after each session (T2-T5) and one month after the end of the sessions
      (T6)), and analyzed using repeated measure analysis of variance (ANOVA) and
      Bonferroni statistical tests. A P value < 0.05 was considered significant.
      Results: The decrease in pain (P=0.000), tenderness (P=0.000) and increase in
      mouth-opening ability (P=0.002) was greater in the TENS and LLL groups than in
      the placebo groups. At the one-month follow-up, significant decrease in pain and
      tenderness was recorded in the TENS and LLL groups (P=0.000). There was no
      significant differences between TENS and LLL and the placebo groups for maximum
      mouth-opening at the end of the study (P=0.692). Conclusion: Using TENS or LLL
      therapy can improve TMD symptoms at least for the short term. Although the
      effects of the placebo played a role in improving symptoms, their effects were
      less important.

PMID- 29071033
TI  - Stimulation Effect of Low Level Laser Therapy on Sciatic Nerve Regeneration in
      Rat.
AB  - Introduction: Recent studies showed that low-level laser therapy (LLLT)
      accelerates the regeneration process of injured peripheral nerve tissue. The
      objective of this study was investigate the effect of LLLT (780 nm) on
      regeneration of injured right sciatic nerve of male Wistar rat. Methods: In this
      research work, the effect of LLLT (780 nm) on the regeneration process and
      reconstruction of injured peripheral right side sciatic nerve was investigated.
      Twelve adult male Wistar rats underwent surgery in aseptic conditions under
      general anesthesia to induce a lesion to their right side sciatic nerve according
      to standard protocol. Before suturing the location, only the experimental group
      was treated by laser. The damaged nerve was directly irradiated with (2 J, 100
      mW, 40 seconds). The irradiation procedure was terminated in 21 days with little
      improvement (4 J, 200 mW, 40 seconds) across the skin surface of experimental
      group. Rats were selected randomly from each group to be sacrificed on different
      periods and histopathological examination was carried out on the extracted
      nerves. Results: Significant acceleration of revascularization and angiogenesis
      of the injury site was observed in the experimental group. Furthermore, a
      reduction of hemorrhages and increase in blood supply was observed. Also,
      Wallerian degeneration decreased while higher axonal density compared to the
      control rats was observed. Moreover, the cross-section analysis of the injured
      area on the 14th and 21st days as post-surgery showed that the nerve sheath
      diameter in the lesion area of the experimental group was reduced. While the
      ratio between thicknesses increased in the control group. Conclusion: The results
      of the current study suggest that laser phototherapy at 780 nm exactly could
      accelerate the regeneration process of injured peripheral nerves tissue.

PMID- 29071034
TI  - Alterations in Auditory Electrophysiological Responses Associated With Temporary
      Suppression of Tinnitus Induced by Low-Level Laser Therapy: A Before-After Case
      Series.
AB  - Introduction: Tinnitus is the phantom auditory perception of sound in the absence
      of an external or internal acoustic stimulus. The treatment is difficult due to
      multiple etiologies and great psychological influence. The purpose of this study
      was to determine alterations in auditory physiological and electrophysiological
      responses associated with temporary suppression of tinnitus induced by low-level
      laser (LLL) irradiation. Methods: This study was conducted on 20 subjects with
      subjective tinnitus. All subjects signed the informed consent form and satisfied
      all the study eligibility criteria. Visual analog scale (VAS) for loudness,
      loudness matching of tinnitus (LMT), pitch matching of tinnitus (PMT), Persian
      tinnitus questionnaire (P-TQ) and Persian-tinnitus handicap inventory (P-THI)
      were conducted pre- and post-low level laser therapy (LLLT) for all the subjects.
      Electrocochleography (ECochG) and distortion product otoacoustic emissions
      (DPOAEs) were recorded in 11 subjects. Continuous wave diode lasers, including
      red (630 nm) and infra-red (808 nm) were applied, and were both designed by the
      Canadian Optic and Laser (COL) Center. Twelve sessions of laser therapy were
      performed, 2 sessions per week for each subject. Total dose was 120 Joule/
      ear/session. Results: LLL irradiation could cause a significant decrease in
      subjective tests scores consisting of VAS for loudness, PMT, P-TQ, P-THI, but did
      not result in a significant improvement of objective evaluating parameters except
      for compound action potential (CAP) amplitude. Conclusion: LLLT might be a
      subjectively effective treatment for short-term improvement of tinnitus. Defining
      a new protocol for optimizing LLLT parameters may be an option to improve
      parameters of objective tests.

PMID- 29071035
TI  - A Comparative Study of 660 nm Low-Level Laser and Light Emitted Diode in
      Proliferative Effects of Fibroblast Cells.
AB  - Introduction: In recent years, low-power lasers have been widely used in
      medicine. With the introduction of affordable light emitted diode (LED), clinical
      application of LED light has become more and more popular. However, some
      researchers believe that due to lack of coherence of the LED light, it can be
      different in terms of biological effects, in comparison with laser. In this
      study, the biological effects of low-level laser (LLL) to those of LED light are
      compared and discussed. Methods: Human skin fibroblast cell line Hu02 was
      irradiated with LLL and LED light with a wavelength of 660 nm, power output of 35
      mW and in continuous mode and the control group was not irradiated. The
      biological effects were compared through analysis of cell proliferation,
      production of reactive oxygen species (ROS) within the cell and rate of cell
      division. Results: Our findings showed that production of ROS within the cell was
      linearly increased both in the LED and laser light irradiated cells. However,
      laser light is more incremental in comparison to LED light. The MTT results
      showed that laser light at low energy density (less than 5 J/cm2) increased the
      rate of cell proliferation after 24 hours. Although, the rate of cell division
      was increased in energy density of 1 J/cm2 compared to the control group, this
      increase was not statistically significant. Discussion: The findings indicated
      that the coherence properties of laser light provided more energy for the cells,
      and in a constant energy density, laser light created more oxidative stresses in
      comparison with LED light.

PMID- 29071036
TI  - Comparison of Er:YAG Laser and Hand Instrumentation on the Attachment of Cultured
      Human Gingival Fibroblasts to Periodontally Involved Root Surfaces.
AB  - Introduction: The present study compared the effects of erbium-doped yttrium
      aluminium garnet (Er:YAG) laser and hand instrumentation on the attachment of
      human gingival fibroblast (HGF) cells to periodontally involved root surfaces.
      Methods: A total of 40 tooth specimens were collected and treated in four
      distinct groups: scaled and root planed with hand instruments, scaled with Er:YAG
      laser, treated with a combination of hand instruments and Er:YAG laser and non
      treated control group. The attachment and proliferation rate of HGF were assessed
      using MTT assay and scanning electron microscope (SEM) examination was used for
      cell morphological evaluation. Results: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,
      5 diphenyl tetrazolium bromide) assay showed significant decrease in HGF cell
      viability in both hand instruments only and combination treated teeth specimens
      compared to control specimens (P<0.05), 24 hours after cell seeding. However, at
      time 48, the cell viability of attached cells in these 2 treated groups was
      almost similar to control. In contrast, at 24 and 48 hours after cell seeding,
      viability of attached cells was higher than control in Er:YAG laser treated only
      specimens (P<0.05). According to SEM study, the laser treated specimens showed
      more surface roughness. Conclusion: Er:YAG laser increased attachment and
      proliferation of HGF cells in comparison to the hand instruments method.

PMID- 29071037
TI  - The Impact of Plasma Treatment of Cercon(r) Zirconia Ceramics on Adhesion to
      Resin Composite Cements and Surface Properties.
AB  - Introduction: In recent years, the use of ceramic base zirconia is considered in
      dentistry for all ceramic restorations because of its chemical stability,
      biocompatibility, and good compressive as well as flexural strength. However, due
      to its chemical stability, there is a challenge with dental bonding. Several
      studies have been done to improve zirconia bonding but they are not reliable. The
      purpose of this research is to study the effect of plasma treatment on bonding
      strength of zirconia. Methods: In this in vitro study, 180 zirconia discs'
      (thickness was 0.85-0.9 mm) surfaces were processed with plasma of oxygen, argon,
      air and oxygen-argon combination with 90-10 and 80-20 ratio (n=30 for each group)
      after being polished by sandblast. Surface modifications were assessed by
      measuring the contact angle, surface roughness, and topographical evaluations.
      Cylindrical Panavia f2 resin-cement and Diafill were used for microshear strength
      bond measurements. The data analysis was performed by SPSS 20.0 software and one
      way analysis of variance (ANOVA) and Tukey test as the post hoc. Results: Plasma
      treatment in all groups significantly reduces contact angle compare with control
      (P=0.001). Topographic evaluations revealed coarseness promotion occurred in all
      plasma treated groups which was significant when compared to control (P<0.05),
      except argon plasma treated group that significantly decreased surface roughness
      (P<0.05). In all treated groups, microshear bond strength increased, except
      oxygen treated plasma group which decreased this strength. Air and argon-oxygen
      combination (both groups) significantly increased microshear bond strength
      (P<0.05). Conclusion: According to this research, plasmatic processing with
      dielectric barrier method in atmospheric pressure can increase zirconia bonding
      strength.

PMID- 29071038
TI  - Evaluation of the Effect of Different Laser Activated Bleaching Methods on Enamel
      Susceptibility to Caries; An In Vitro Mode.
AB  - Introduction: Today, bleaching is a routine noninvasive alternative for treatment
      of discolored teeth. The aim of this study was to determine whether conventional
      or laser activated bleaching predispose teeth to develop caries or not. Methods:
      Sixty human molars were mounted on acrylic cylinders and their Knoop
      microhardness (KHN) as well as DIAGNOdent (DD) values were recorded. They were
      divided into 4 experimental groups; G1) conventional bleaching with 40% hydrogen
      peroxide gel, G2) Diode laser assisted bleaching with same gel, G3) Nd:YAG laser
      assisted bleaching with the same gel, G4) control group. After bleaching, all
      samples were subjected to a three day pH cycling regimen and then, KHN and DD
      values were measured. Results: All groups had significant reduction in KHN
      values. It seems that there is no statistically meaningful difference between
      changes in enamel microhardness of the sample groups and all groups have changed
      in a similar amount. Reduction of DD scores were significant in Diode laser and
      conventional groups, however changes in Nd:YAG laser and control groups were not
      significant. Changes in DD values have followed a similar pattern among groups,
      except in G1- G4 and G2-G4 couples. Conventional and diode laser groups had a
      meaningful difference in reduction of DD values in comparison with the control
      group. Conclusion: It can be concluded that bleaching whether conventional or
      laser activated, does not make teeth vulnerable to develop carious lesions.

PMID- 29071039
TI  - Laser Assisted Treatment of Extra Oral Cutaneous Sinus Tract of Endodontic
      Origin: A Case Report.
AB  - Introduction: Sinus tract (or fistula) is a common manifestation of pulpal
      necrosis with periapical pathosis that requires conventional or rarely surgical-
      endodontic treatment in order to heal. It is mainly identified intraorally and in
      rare cases manifestation is extra orally, which may frequently be misdiagnosed
      with cutaneous lesion and incorrectly treated. New technologies such as lasers
      have been developed as adjuncts to standard endodontic antimicrobial procedures
      in order to increase the success rate of endodontic therapy while complying with
      the desire of saving a natural tooth. Case Presentation: Herein, we present a
      clinical case of extra oral sinus tract with periodic pus drainage that was
      successfully treated by combining conventional endodontic therapy, intra canal
      photodynamic therapy (PDT), extra oral low level laser therapy (LLLT) and laser
      treatment for extra oral fistula. Conclusion: Treatment of the odontogenic lesion
      among with the extra oral lesion was an ingenious and successful technique which
      was achieved via laser technology and winded up to patient's consent and
      satisfactory results.

PMID- 29071040
TI  - Cost-effectiveness of timely versus delayed primary total hip replacement in
      Germany: A social health insurance perspective.
AB  - Without clinical guideline on the optimal timing for primary total hip
      replacement (THR), patients often receive the operation with delay. Delaying THR
      may negatively affect long-term health-related quality of life, but its economic
      effects are unclear. We evaluated the costs and health benefits of timely primary
      THR for functionally independent adult patients with end-stage osteoarthritis
      (OA) compared to non-surgical therapy followed by THR after progression to
      functional dependence (delayed THR), and non-surgical therapy alone (Medical
      Therapy), from a German Social Health Insurance (SHI) perspective. Data from hip
      arthroplasty registers and a systematic review of the published literature were
      used to populate a tunnel-state modified Markov lifetime model of OA treatment in
      Germany. A 5% annual discount rate was applied to costs (2013 prices) and health
      outcomes (Quality Adjusted Life Years, QALY). The expected future average cost of
      timely THR, delayed THR and medical therapy in women at age 55 were ?27,474,
      ?27,083 and ?28,263, and QALYs were 20.7, 16.7, and 10.3, respectively. QALY
      differences were entirely due to health-related quality of life differences. The
      discounted cost per QALY gained by timely over delayed (median delay of 11 years)
      THR was ?1270 and ?1338 in women treated at age 55 and age 65, respectively, and
      slightly higher than this for men. Timely THR is cost-effective, generating large
      quality of life benefits for patients at low additional cost to the SHI. With
      declining healthcare budgets, research is needed to identify the characteristics
      of those able to benefit the most from timely THR.

PMID- 29071042
TI  - Body mass index and severity of parkinsonism in multiple system atrophy.

PMID- 29071041
TI  - Risk factors associated with post-stroke dementia: a systematic review and meta
      analysis.

PMID- 29071043
TI  - Migraine headache in patients with idiopathic intracranial hypertension.
AB  - Migraine is a neurological disorder that afflicts many people in the world and
      can cause severe disability during the attacks. The pathophysiology of migraine
      is complex and not fully understood. It seems that migraine is common in
      idiopathic intracranial hypertension (IIH). However, the association between
      migraine headache and IIH is still unclear. The present study was conducted to
      assess the prevalence of migraine headache and associated factors in IIH
      patients. In this cross-sectional study, a total of 68 patients diagnosed with
      IIH underwent a medical history interview and a neurological examination. The
      diagnosis of migraine was based on the four diagnostic criteria of the
      International Classification of Headache Disorders 3rd edition. Forty-five
      patients (63.2%) met the diagnostic criteria of migraine headache. There was no
      significant difference between patients with and without migraine headache in
      respect of their age, gender, body mass. This study revealed high prevalence of
      migraine headache in IIH patients; appropriate treatment can reduce their
      headache and prevent unnecessary treatments for IIH.

PMID- 29071044
TI  - Chiari type I malformation with cervicothoracic syringomyelia subterfuge as flail
      arm syndrome.
AB  - Chiari type I malformation with cervicothoracic syringomyelia although very
      common in clinical practice usually in children can progress slowly and mimic
      muscular dystrophies in adulthood. We present a rare adult case of Chiari type I
      malformation with cervicothoracic syringomyelia subterfuge as Flail arm syndrome.
      A 44-year-old man was diagnosed with congenital type I Chiari malformation with
      cervicothoracic syringomyelia about 21 years ago without surgery. His health
      status deteriorated over the years until 21 days prior to presentation when he
      had severe pain in the right knee. In his upper limbs, he had bilateral
      corresponding severe weakness of 0/5 proximal strength and 0/5 strength in his
      distal muscles. Magnetic resonance imaging (MRI) revealed an enlargement of the
      spinal cord from C1-C4 level with a mass that appeared hypo-dense on T1 and
      hyperdense on T2. Syringomyelia is a potentially serious neurologic condition
      that can mimic other neuromuscular disorders. Early detection and diagnosis with
      MRI is crucial to avoid irreversible neurological complications. We suggest that
      whether asymptomatic or symptomatic, decompressive surgery should be carried out
      to allow for free flow of cerebrospinal fluid thereby improving the quality of
      life for the patient.

PMID- 29071045
TI  - Repeated spontaneous clearance of hepatitis C virus infection in the setting of
      long-term non-progression of HIV infection.
AB  - Hepatitis C Virus (HCV) and human immunodeficiency virus (HIV) are global
      pandemics that affect 170 million and 35 million individuals, respectively. Up to
      45% of individuals infected with HCV clear their infections spontaneously -
      correlating to factors like aboriginal descent and some host specific immune
      factors. HIV, however, establishes true latency in infected cells and cannot be
      cured. In the setting of longterm non-progressors (LTNPs) of HIV, a state of
      immune preservation and low circulating viral load is established. Regarding
      HIV/HCV co-infection, little is known about the relationship between spontaneous
      clearance of HCV infection and long-term control of HIV infection without medical
      intervention. We describe a case of a HIV-infected female defined as a LTNP in
      whom spontaneous clearance of HCV was documented on multiple occasions. Similar
      cases should be documented and identified in an effort to develop novel
      hypotheses about the natural control of these infections and inform research on
      immune-based interventions to control them.

PMID- 29071046
TI  - Native join Propionibacterium septic arthritis.
AB  - Propionibacterium species are associated with normal skin flora and cultures may
      be dismissed as contaminants. They are increasingly recognized as a cause of
      septic arthritis following shoulder arthroplasty and arthrotomy. We identified
      three cases of Propionibacterium septic arthritis in native joints mimicking
      atypical osteoarthritis and review the literature, clinical course, and treatment
      of 18 cases. Two cases of Propionibacterium acne in native knee joints and one in
      a sternoclavicular joint are described. A literature search for Propionibacterium
      septic arthritis was performed. Clinical course, treatment, and outcome are
      reviewed for all cases. Our three cases were combined with 15 cases from the
      literature. Fourteen cases showed few signs of acute infection, slow culture
      growth, and delayed diagnosis. In 3 cases an early culture was dismissed as a
      contaminant. Six cases were reported as caused by recent arthrocentesis. Fifteen
      cases were cured with antibiotics, although 5 of these 15 also required surgical
      intervention. Two patients were diagnosed while undergoing surgery for
      osteoarthritis. Four patients required arthroplasty and two of our patients will
      require arthroplasty for good functional results. Propionibacterium as a cause of
      septic arthritis in native joints demonstrates few signs of acute infection,
      presents with prolonged course, and is often misdiagnosed or unsuspected.
      Anaerobic growth may be delayed or missed altogether, and outcomes are
      consequently poor. Consider Propionibacterium septic arthritis in atypical
      osteoarthritis prior to arthroplasty.

PMID- 29071047
TI  - Patterns of vitamin D, parathyroid hormone and c-terminal telopeptide of collagen
      type 1 in Caucasian and African descent HIV-infected populations in Central
      Europe.
AB  - Risk factors for bone loss in HIV patients might differ or have a different
      impact in African descent compared to Caucasian populations. The aim of the paper
      is to analyze the relevance of risk factors on surrogate markers of bone
      metabolism in HIV-infected African descent and Caucasian patients. This is a
      cross-sectional study in a single HIV-specialized research and clinical care
      center in Munich, Germany. We included 889 patients in the study, among them 771
      Caucasians (86.7%). Only in Caucasians lower vitamin D levels [OR: 2.5 (95CI: 1.6
      3.7)], lower calcium levels [OR: 1.8 (1.2-2.8)], and the use of tenofovir
      disoproxil fumarate [OR: 2.8 (1.8-4.4)] were significantly associated with
      elevated PTH in multivariate analysis. Likewise, only in Caucasians elevated PTH
      was significantly associated with elevated markers of c-terminal telopeptides of
      collagen type 1 (beta-CTX) [OR: 1.7 (1.0-3.0)]. Effects of traditional risk
      factors for secondary hyperparathyroidism and increased markers of bone turn-over
      seem to be less distinct in African descent HIV patients. The clinical impact and
      generalizability of this finding as well as the significance of vitamin D
      supplementation in African descent patients therefore warrants further
      investigation.

PMID- 29071048
TI  - Changes in antimicrobial prescribing behavior after the introduction of the
      antimicrobial stewardship program: A pre- and post-intervention survey.
AB  - The introduction of an antimicrobial stewardship (AMS) program is associated with
      a change in antimicrobial prescribing behavior. A proposed mechanism for this
      change is by impacting the prescribing etiquette described in qualitative
      studies. This study sought to detect a change in prescribing attitudes 12 months
      after the introduction of AMS and gauge utility of various AMS interventions.
      Surveys were distributed to doctors in two regional Australian hospitals on a
      convenience basis 6 months before, and 12 months after, the introduction of AMS.
      Agreement with 20 statements describing attitudes (cultural, behavioral and
      knowledge) towards antimicrobial prescribing was assessed on a 4-point Likert
      scale. Mean response scores were compared using the Wilcoxon Rank sum test. 155
      responses were collected before the introduction of AMS, and 144 afterwards.
      After the introduction of AMS, an increase was observed in knowledge about
      available resources such as electronic decision support systems (EDSS) and
      therapeutic guidelines, with raised awareness about the support available through
      AMS rounds and the process to be followed when prescribing restricted
      antimicrobials. Additionally, doctors were less likely to rely on pharmacy to
      ascertain when an antimicrobial was restricted, depend on infectious diseases
      consultant advice and use past experience to guide antimicrobial prescribing.
      Responses to this survey indicate that positive changes to the antimicrobial
      prescribing etiquette may be achieved with the introduction of an AMS program.
      Use of EDSS and other resources such as evidence-based guidelines are perceived
      to be important to drive rational antimicrobial prescribing within AMS programs.

PMID- 29071049
TI  - Clinical and experimental efficacy of gemtuzumab ozogamicin in core binding
      factor acute myeloid leukemia.

PMID- 29071050
TI  - Single step multiple genotyping by MALDI-TOF mass spectrometry, for evaluation of
      minor histocompatibility antigens in patients submitted to allogeneic stem cell
      transplantation from HLA-matched related and unrelated donor.

PMID- 29071051
TI  - Safety and efficacy of ibrutinib in a patient with severe renal impairment.

PMID- 29071052
TI  - Managing acute promyelocytic leukemia in patients belonging to the Jehovah's
      Witness congregation.

PMID- 29071053
TI  - Two cases of angioimmunoblastic T-cell lymphoma with concomitant positive
      serology for acute Epstein-Barr virus infection.

PMID- 29071054
TI  - Enterococcus raffinosus infection with atypical hemolytic uremic syndrome in a
      multiple myeloma patient after autologous stem cell transplant.

PMID- 29071055
TI  - Gluteal artery injuries including pseudoaneurysm associated with powered bone
      marrow biopsies.

PMID- 29071056
TI  - Therapy-related myeloid neoplasms as a concerning complication in acute
      promyelocytic leukemia.

PMID- 29071057
TI  - Sociodemographic, lifestyle and therapeutic predictors of 2- year survival in HIV
      infected persons receiving antiretroviral therapy in Benin.

PMID- 29071058
TI  - The short hyperacusis questionnaire: A tool for the identification and
      measurement of hyperacusis in the Italian tinnitus population.

PMID- 29071059
TI  - Day-case management of chronic suppurative otitis media with cholesteatoma with
      canal wall down technique surgery: long-term follow-up.

PMID- 29071060
TI  - Cervical fistula caused by submandibular sialolithiasis.

PMID- 29071062
TI  - Glycated hemoglobin and red blood cell indices in non-diabetic pregnant women.

PMID- 29071061
TI  - Gut microbiota's effect on mental health: The gut-brain axis.

PMID- 29071063
TI  - Mucoepidermoid carcinoma of palate - a rare entity.

PMID- 29071064
TI  - Reducing shade avoidance responses in a cereal crop.
AB  - Several researchers have hypothesized that shade avoidance behaviour is favoured
      by natural selection because it increases the fitness of individuals. Shade
      avoidance can be disadvantageous for crops, however, because it reduces
      allocation of resources to reproductive yield, increases the risk of lodging and
      reduces weed suppression. One approach to develop varieties with reduced shade
      avoidance and enhanced agronomic performance is by inducing mutations followed by
      phenotypic screening. We treated spring wheat seeds with ethyl methanesulfonate
      and screened the seedlings repeatedly under green filters for plants showing
      reduced elongation of the first leaf sheath and second leaf lamina. The shade
      avoidance responses of five promising mutant lines were further compared to non
      mutated plants in a climate chamber experiment with added far-red light. Two of
      the selected lines displayed significantly reduced elongation under all light
      treatments while two lines showed reduced elongation only in added far-red light.
      The most promising mutant line did not differ in height from the non-mutated
      cultivar in neutral light, but elongated 20.6% less in strong far-red light. This
      traditional forward approach of screening mutagenized spring wheat produced
      plants with reduced shade avoidance responses. These mutants may generate new
      molecular handles to modify the reaction of plants to changes in light spectral
      distribution in traditional and novel cultivation systems.

PMID- 29071065
TI  - Logarithmic distributions prove that intrinsic learning is Hebbian.
AB  - In this paper, we document lognormal distributions for spike rates, synaptic
      weights and intrinsic excitability (gain) for neurons in various brain areas,
      such as auditory or visual cortex, hippocampus, cerebellum, striatum, midbrain
      nuclei. We find a remarkable consistency of heavy-tailed, specifically lognormal,
      distributions for rates, weights and gains in all brain areas. The difference
      between strongly recurrent and feed-forward connectivity (cortex vs. striatum and
      cerebellum), neurotransmitter (GABA (striatum) or glutamate (cortex)) or the
      level of activation (low in cortex, high in Purkinje cells and midbrain nuclei)
      turns out to be irrelevant for this feature. Logarithmic scale distribution of
      weights and gains appears as a functional property that is present everywhere. 
      Secondly, we created a generic neural model to show that Hebbian learning will
      create and maintain lognormal distributions. We could prove with the model that
      not only weights, but also intrinsic gains, need to have strong Hebbian learning
      in order to produce and maintain the experimentally attested distributions. This
      settles a long-standing question about the type of plasticity exhibited by
      intrinsic excitability.

PMID- 29071067
TI  - The Birmingham experience of high-pressure methylene blue dye test during primary
      and revisional bariatric surgery: A retrospective cohort study.
AB  - INTRODUCTION: Leak following bariatric surgery continues to be associated with
      morbidity and rarely mortality. With improvement in surgical techniques and
      stapler design, leak rates have reduced drastically. Intra-operative high
      pressure Methylene blue leak test (HPMB) is one of the techniques employed to
      confirm integrity of anastomoses and staple lines. Despite this, evidence for its
      use remains limited. We evaluated the role of HPMB in detecting and preventing
      leaks. METHODS: A retrospective cohort of consecutive patients who underwent
      primary or revisional Laparoscopic Sleeve Gastrectomy (SG) or Laparoscopic Roux
      en-Y Gastric bypass (RYGB) under the care of five surgeons in three centres
      across Birmingham, UK, between 2012 and 2016 were assessed. All patients had
      routine HPMB at the end of the procedure. Demographics, HPMB positivity, and post
      operative leaks were recorded. RESULTS: 924 patients underwent bariatric surgery:
      696(75.3%) RYGB, and 225(24.3%) SG. 85(9.2%) were revisional procedures. Two HPMB
      were positive, which necessitated staple or suture line reinforcement with
      sutures intra-operatively. The patients had an uneventful recovery. 5 patients
      had postoperative leaks, all of whom had negative intraoperative HPMB: 3 SG
      patients; and 2 RYGB patients (gastro-jejunostomy anastomotic leaks). There was
      no statistically significant relationship between positive HPMB and anastomotic
      leak (Fishers exact test; p = 1). CONCLUSION: Despite routine use of methylene
      blue dye test in 924 patients, there were only two positive tests. Whilst HPMB
      may demonstrate technical failure, this study suggests that there is no role for
      its routine use in primary bariatric surgery. Discontinuation of this practice
      would reduce risk of anaphylaxis to the dye, cost, and intra-operative time.

PMID- 29071069
TI  - Water fleas stand the heat and stay in the city.

PMID- 29071068
TI  - The ligament of Parks as a key anatomical structure for safer hemorrhoidectomy:
      Anatomic study and a simple surgical note.
AB  - Hemorrhoids are a common anal disorder which affects both men and women of all
      ages. One out of ten patients with hemorrhoidal disease, requires surgical
      treatment. Unfortunately though, hemorrhoidectomy is closely related to
      complications that can be present early or late postoperatively. In the present
      manuscript, the safe surgical technique which emphasizes to the identification of
      the key anatomical structure of the ligament of Parks (Trietz's muscle) is
      adequately described. A total of 200 patients with grades III and IV hemorrhoids,
      underwent Milligan-Morgan or Ferguson's hemorrhoidectomy. The mucosal ligament of
      Parks was identified to all patients and was used as a key anatomical structure
      through the excision of the hemorrhoids. Its identification guides surgeons
      during the operation and reduces the major problem of postoperative
      complications. Finally, since the mucosal ligament of Parks represents a
      constantly identifiable landmark, it allows simple and reliable identification of
      the internal sphincter muscle and minimizes the probability of postoperative
      complications.

PMID- 29071066
TI  - The emerging role of PET imaging in dementia.
AB  - A compelling need in the field of neurodegenerative diseases is the development
      and validation of biomarkers for early identification and differential diagnosis.
      The availability of positron emission tomography (PET) neuroimaging tools for the
      assessment of molecular biology and neuropathology has opened new venues in the
      diagnostic design and the conduction of new clinical trials. PET techniques,
      allowing the in vivo assessment of brain function and pathology changes, are
      increasingly showing great potential in supporting clinical diagnosis also in the
      early and even preclinical phases of dementia. This review will summarize the
      most recent evidence on fluorine-18 fluorodeoxyglucose-, amyloid -, tau -, and
      neuroinflammation - PET tools, highlighting strengths and limitations and
      possible new perspectives in research and clinical applications. Appropriate use
      of PET tools is crucial for a prompt diagnosis and target evaluation of new
      developed drugs aimed at slowing or preventing dementia.

PMID- 29071070
TI  - 'Massilibacteroides vaginae' gen. nov., sp. nov., a new genus within the family
      of Bacteroidaceae isolated from a patient with vaginosis.
AB  - 'Massilibacteroides vaginae' sp. nov. strain MV12T is the type strain of
      'Massilibacteroides' gen. nov., a new genus within the family of
      Porphyromonadaceae. This strain was isolated in Marseille from a patient with
      vaginosis. 'Massilibacteroides vaginae' is a Gram-negative, aero-anaerobic
      bipolar bacillus. Here we describe the phenotypic characteristics and complete
      genome sequence of this bacterium. The EMBL accession number is FXDJ00000000
      (FXDJ01000001-FXDJ01000009), and its genome consists of nine scaffolds. The
      strain was deposited in two culture collections under the numbers CSUR P1477 and
      DSM 100704.

PMID- 29071072
TI  - Effect of high-flow nasal therapy during acute aerobic exercise in patients with
      chronic obstructive pulmonary disease after exacerbation: protocol for a
      randomised, controlled, cross-over trial.
AB  - INTRODUCTION: Early pulmonary rehabilitation is recommended after a severe
      exacerbation of chronic obstructive pulmonary disease (COPD). However, this is
      difficult to implement, particularly for exercise training. High-flow nasal
      therapy (HFNT) may reduce the work of breathing and dyspnoea and may improve
      exercise tolerance. METHODS AND ANALYSIS: This is a single-centre, prospective,
      controlled, randomised, cross-over study. Eligible patients will have a diagnosis
      of COPD (postbronchodilator forced expiratory volume in 1 s/forced vital capacity
      ratio of <0.7). Two constant work rate exercise tests at 80% of the peak work
      rate will be carried out on two consecutive days with and without HFNT. The
      primary outcome will be the difference in endurance time between the two
      conditions. Secondary outcomes will be the change in muscle oxygenation during
      exercise, dyspnoea and muscle fatigue, respiratory muscle strength after
      exercise, respiratory rate, cardiac frequency, transcutaneous CO2 pressure and
      pulsed O2 saturation. Nineteen patients will be included. Data will be analysed
      as intention to treat by a blinded statistician. ETHICS AND DISSEMINATION: Ethics
      approval has been obtained from the Ethics Committees Nord-Ouest III, Caen,
      France (N degrees  ID RCB: 2016-A01325-46). The study will begin in April 2017
      for a duration of 2 years. The results of the trial will be presented at national
      and international meetings and published in peer-reviewed journals. TRIAL
      REGISTRATION NUMBER: NCT03058081.

PMID- 29071071
TI  - Environmental triggers of COPD symptoms: a case cross-over study.
AB  - INTRODUCTION: This study investigated the hypothesis that common environmental
      chemical exposures with known irritant or sensitising properties trigger
      exacerbations for patients with chronic obstructive pulmonary disease (COPD).
      METHODS: We conducted a case cross-over study in 168 patients with COPD who were
      members of a disease management group in central Massachusetts. Participants
      completed a baseline health survey and several short exposure surveys. Exposure
      surveys were administered by a nurse when a participant telephoned to report an
      exacerbation (case periods) and at a maximum of three randomly identified control
      periods when they were not experiencing an exacerbation. We compared exposures in
      the week preceding an exacerbation with exposures in normal (non-exacerbation)
      weeks. The questionnaire assessed short-term (1 week) home, community and
      workplace activities and exposures that may be associated with COPD exacerbation.
      RESULTS: Self-reported exercise was negatively associated with exacerbation
      (OR=0.59, 95% CI: 0.35 to 1.00). Among the environmental chemical exposures, car
      and truck exhaust (OR=4.36, 95% CI: 1.76 to 10.80) and use of scented laundry
      products (OR=2.69, 95% CI: 1.31 to 5.52) showed strong positive effects. Self
      reported respiratory infections were strongly associated with exacerbation
      (OR=7.90, 95% CI 4.29 to 14.50). Variations in outdoor temperature were
      associated with COPD exacerbation risk (moderate versus cold temperature OR=1.95,
      95% CI 1.09 to 3.49 and warm versus cold OR=0.43, 95% CI: 0.26 to 0.70).
      CONCLUSIONS: These results suggest that some environmental chemical exposures may
      play a role in triggering COPD exacerbations. If confirmed, they may provide
      useful guidance for patients with COPD to better manage their disease.

PMID- 29071073
TI  - Rapid decline in lung function in healthy adults predicts incident excess urinary
      albumin excretion later in life.
AB  - INTRODUCTION: Chronic lung disease, often characterised by rapid decline in lung
      function, is associated with vascular endothelial dysfunction (characterised by
      moderate to severe excess urinary albumin excretion (eUAE) but their longitudinal
      relationship is inadequately studied. In a bidirectional longitudinal examination
      of healthy adults, we analysed the following two hypotheses: (1) rapid decline
      (ie, highest tertile of lung function decline) predicts eUAE and (2) eUAE
      predicts rapid decline. METHODS: We performed a secondary data analysis from 3052
      eligible participants from the Coronary Artery Risk Development in Young Adults
      (CARDIA) study. For analysis 1, the predictor was rapid decline in lung function
      between the peak value (attained at or before CARDIA visit year 10 or Y10 at a
      mean age of 35 years) and Y20; and the outcome was incident eUAE at Y20 and/or
      Y25. For analysis 2, the predictor was eUAE at Y10 and the outcome was rapid
      decline between Y10 and Y20. RESULTS: After adjustment for covariates in analysis
      1, rapid decline in FEV1 or FVC between peak and Y20 predicted incident eUAE at
      Y20 and/or Y25 (OR 1.51 and 1.44, respectively; p<=0.05 for both analyses). In
      analysis 2, eUAE at Y10 did not predict subsequent rapid decline. CONCLUSIONS:
      Healthy adults with rapid decline in lung function are at risk for developing
      vascular endothelial dysfunction, as assessed by incident eUAE, later in life.

PMID- 29071074
TI  - Long-term outcomes of patients with pulmonary arteriovenous malformations
      considered for lung transplantation, compared with similarly hypoxaemic cohorts.
AB  - INTRODUCTION: Pulmonary arteriovenous malformations (PAVMs) may not be amenable
      to treatment by embolisation or surgical resection, and many patients are left
      with significant hypoxaemia. Lung transplantation has been undertaken. There is
      no guidance on selection criteria. METHODS: To guide transplantation listing
      assessments, the outcomes of the six patients who had been considered for
      transplantation were compared with a similarly hypoxaemic patient group recruited
      prospectively between 2005 and 2016 at the same UK institution. RESULTS: Six
      patients had been formally considered for lung transplantation purely for PAVMs.
      One underwent a single lung transplantation for diffuse PAVMs and died within 4
      weeks of surgery. The other five were not transplanted, in four cases at the
      patients' request. Their current survival ranges from 16 to 27 (median 21) years
      post-transplant assessment. Of 444 consecutive patients with PAVMs recruited
      between 2005 and 2016, 42 were similarly hypoxaemic to the 'transplant
      considered' cohort (SaO2 <86.5%). Hypoxaemic cohorts maintained arterial oxygen
      content (CaO2) through secondary erythrocytosis and higher haemoglobin. The
      'transplant-considered' cohort had similar CaO2 to the hypoxaemic comparator
      group, but higher Medical Research Council (MRC) dyspnoea scores (p=0.023),
      higher rates of cerebral abscesses (p=0.0043) and higher rates of venous
      thromboemboli (p=0.0009) that were evident before and after the decision to list
      for transplantation. CONCLUSIONS: The non-transplanted patients demonstrated
      marked longevity. Symptoms and comorbidities were better predictors of health
      than oxygen measurements. While a case-by-case decision, weighing survival
      estimates and quality of life will help patients in their decision making, the
      data suggest a very strong case must be made before lung transplantation is
      considered.

PMID- 29071075
TI  - Evaluation by various methods of the physiological mechanism of a high-flow nasal
      cannula (HFNC) in healthy volunteers.
AB  - INTRODUCTION: Several reports have described the usefulness of a high-flow nasal
      cannula (HFNC). However, the physiological mechanisms of this system are unclear.
      In the current study, various methods were used to investigate the physiological
      mechanisms of an HFNC in healthy volunteers. METHODS: The physiological
      mechanisms of the constant-flow and constant-pressure models of HFNC were studied
      in 10 healthy volunteers by the oesophageal balloon method, the electrical
      impedance method and the forced oscillation technique (FOT). RESULTS: The tidal
      volume (TV) increased markedly during HFNC (off, 30 L/min, 50 L/min: 685.6+/
      236.5 mL, 929.8+/-434.7 mL, 968.8+/-451.1 mL). The end-inspiratory oesophageal
      pressure (EIOP) was not significantly different, but there was a tendency for it
      to decrease. HFNC 30 L/min and 50 L/min, the increment in TV and the difference
      in EIOP showed strong negative correlations (p=0.0025, 0.003). The end-expiratory
      oesophageal pressure (EEOP) increased. The respiratory system reactance at 5 Hz
      (X5) by FOT decreased significantly. There was a flow rate-dependent EEOP
      increase, and the positive end-expiratory pressure (PEEP) effect of HFNC was
      confirmed. There was a correlation between the difference in X5 and the
      difference in EEOP during HFNC 30 L/min and 50 L/min, with correlation
      coefficients of 0.534 and 0.404 (p=0.112, 0.281). The amount of change in EEOP
      and the fluctuation in X5 were positively correlated. CONCLUSIONS: The PEEP
      effect of HFNC was confirmed by the electrical impedance method and FOT. The
      increment in TV and the difference in EIOP of HFNC showed strong negative
      correlations.

PMID- 29071076
TI  - Burden of bacterial upper respiratory tract pathogens in school children of
      Nepal.
AB  - INTRODUCTION: Respiratory tract infections are one of the most common human
      infections in all age group and important cause of mortality and morbidity
      worldwide. Most bacterial upper respiratory tract infections are vaccine
      preventable. This study aimed to determine the prevalence of carrier state of
      bacterial upper respiratory tract pathogens among school children. It also aimed
      to study their antibiograms. METHODS: The specimen from posterior pharyngeal wall
      and tonsils were collected from 204 participants on calcium alginate coated swabs
      (HiMedia). Isolates were identified by standard microbiological methods and
      tested for in vitro antibiotic susceptibility testing by modified Kirby-Bauer
      disc diffusion method. RESULTS: In this study, Streptococcus pneumoniae (16.6%)
      was the most common bacterial pathogen recovered, followed by Staphylococcus
      aureus (14.7%), beta-haemolytic streptococci (non-Group A) (8.8%), Streptococcus
      pyogenes (5.3%) and Corynebacterium diphtheriae (3.4%). The Gram negative
      bacteria were Klebsiella pneumoniae (4.9%), Haemophilus influenzae (3.4%) and
      Neisseria meningitidis (1.4%). Important findings in antibiogram include high
      resistance of Streptococcus pneumoniae to penicillin (91.17%) and resistance of
      S. aureus to oxacillin (23.3%). CONCLUSION: Pharyngeal colonisation by S.
      pneumoniae was found high among school children and this calls for an urgent need
      to include pneumococcal vaccine in routine national immunisation schedule of
      Nepal given the high burden of invasive pneumococcal disease. Despite expected
      universal vaccination, pharyngeal colonisation by C. diphtheriae is possible and
      there is possibility of transmission of these respiratory pathogens to other
      healthy children.

PMID- 29071077
TI  - Assessing the use of BreatheSmart(r) mobile technology in adult patients with
      asthma: a remote observational study.
AB  - INTRODUCTION: Non-adherence to asthma daily controller medications is a common
      problem, reported to be responsible for 60% of asthma-related hospitalisations.
      The mean level of adherence for asthma medications is estimated to be as low as
      22%. Therefore, objective measurements of adherence to medicine are necessary.
      This virtual observational study is designed to measure the usability of an
      electronic monitoring device platform that measures adherence. Understanding how
      patients use the BreatheSmart mobile technology at home is essential to assess
      its feasibility as a solution to improve medication adherence. We anticipate this
      approach can be applied to real-world environments as a cost-effective solution
      to improve medication adherence. METHODS AND ANALYSIS: This is a virtual 6-month
      observational study of 100 adults (>=18 years) with an asthma diagnosis, using
      inhaled corticosteroids for at least 3 months. Participants will be recruited in
      the USA through ad placements online. All participants receive wireless Bluetooth
      enabled inhaler sensors that track medication usage and an mSpirometerTM capable
      of clinical-grade lung function measurements, and download the BreatheSmart
      mobile application that transmits data to a secure server. All analyses are based
      on an intention-to-treat. Usability is assessed by patient questionnaires and
      question sessions. Simple paired t-test is used to assess significant change in
      Asthma Control Test score, quality of life (EuroQol-5D questionnaire) and lung
      function. ETHICS AND DISSEMINATION: No ethical or safety concerns pertain to the
      collection of these data. Results of this research are planned to be published as
      soon as available. TRIAL REGISTRATION NUMBER: NCT03103880.

PMID- 29071079
TI  - Singing for Lung Health: a qualitative assessment of a British Lung Foundation
      programme for group leaders.
AB  - INTRODUCTION: Singing for Lung Health (SLH) groups are an increasingly popular
      intervention for people with respiratory disease. There are limited data as to
      how these groups should be developed and run. We aimed to evaluate the experience
      of singing leaders both to assess the training provided by the British Lung
      Foundation (BLF) and to provide information to guide future development of
      programmes. METHODS: A convenience sample of 15 leaders who had received BLF SLH
      training participated in the BLF service evaluation. Fifteen singing groups were
      observed, and singing leader interviews and questionnaires were collected.
      Inductive themes from the qualitative data were the primary outcome. The content
      of observed singing groups was also rated against the training leaders had
      received. RESULTS: Singing leaders valued the BLF training but felt that a
      significant level of expertise is required before joining. Singing leaders often
      found setting up groups challenging and some found clinician support beneficial.
      There were important technical aspects of running a lung health group including
      issues around content, for example, choice of repertoire to suit breathing
      pattern, and delivery, for example, pace, rhythm and management of group
      dynamics. Leaders said that group participants reported physical health
      improvements such as reduced breathlessness on activity. The content and delivery
      of singing classes observed displayed a good level of fidelity, suggesting that
      SLH training is effective. CONCLUSION: The experience of the leaders highlights
      the requirements, support and technical skills needed to run SLH groups, which
      have features distinct from generic community singing groups.

PMID- 29071078
TI  - Respiratory symptoms are more common among short sleepers independent of obesity.
AB  - INTRODUCTION: Sleep length has been associated with obesity and various adverse
      health outcomes. The possible association of sleep length and respiratory
      symptoms has not been previously described. The aim of this study was to
      investigate the association between sleep length and respiratory symptoms and
      whether such an association existed independent of obesity. METHODS: This is a
      multicentre, cross-sectional, population-based study performed in 23 centres in
      10 different countries. Participants (n=5079, 52.3% males) were adults in the
      third follow-up of the European Community Respiratory Health Survey III. The
      mean+/-SD age was 54.2+/-7.1 (age range 39-67 years). Information was collected
      on general and respiratory health and sleep characteristics. RESULTS: The mean
      reported nighttime sleep duration was 6.9+/-1.0 hours. Short sleepers (<6 hours
      per night) were n=387 (7.6%) and long sleepers (>=9 hours per night) were n=271
      (4.3%). Short sleepers were significantly more likely to report all respiratory
      symptoms (wheezing, waking up with chest tightness, shortness of breath,
      coughing, phlegm and bronchitis) except asthma after adjusting for age, gender,
      body mass index (BMI), centre, marital status, exercise and smoking. Excluding
      BMI from the model covariates did not affect the results. Short sleep was related
      to 11 out of 16 respiratory and nasal symptoms among subjects with BMI >=30 and 9
      out of 16 symptoms among subjects with BMI <30. Much fewer symptoms were related
      to long sleep, both for subjects with BMI <30 and >=30. CONCLUSIONS: Our results
      show that short sleep duration is associated with many common respiratory
      symptoms, and this relationship is independent of obesity.

PMID- 29071080
TI  - Description of the protocol for the PRACTICAL study: a randomised controlled
      trial of the efficacy and safety of ICS/LABA reliever therapy in asthma.
AB  - INTRODUCTION: In adult asthma, combination inhaled corticosteroid (ICS)/fast
      onset long-acting beta agonist (LABA) used solely as reliever therapy may
      represent an effective and safe alternative to ICS maintenance and short-acting
      beta agonist (SABA) reliever therapy. OBJECTIVE: To compare the efficacy and
      safety of ICS/fast-onset LABA reliever therapy with ICS maintenance and SABA
      reliever therapy in adults with asthma. METHODS AND ANALYSIS: A 52-week, open
      label, parallel group, multicentre, phase III randomised controlled trial with
      1:1 randomisation to either budesonide/formoterol Turbuhaler 200/6 ug, one
      actuation as required for symptom relief, or budesonide Turbuhaler 200 ug, one
      actuation twice daily and terbutaline Turbuhaler 250 ug, two actuations as
      required for symptom relief. 890 adults aged 18-75 years with asthma for whom
      maintenance ICS and SABA reliever therapy is indicated by current guidelines will
      be recruited in New Zealand. The primary outcome variable is the rate of severe
      exacerbations per patient per year. This study will investigate a novel treatment
      regimen that might lead to a paradigm shift in asthma management for adults for
      whom guidelines currently recommend maintenance ICS and SABA reliever therapy.
      ETHICS AND DISSEMINATION: Ethical approval has been granted (15/NTB/178). Study
      findings will be published according to Iinternational Committee of Medical
      Journal Editors' recommendations. TRIAL REGISTRATION NUMBER: ACTRN12616000377437;
      Pre-results.

PMID- 29071082
TI  - Adjuncts for sputum clearance in COPD: clinical consensus versus actual use.
AB  - INTRODUCTION: Oscillatory positive pressure devices (OPEP) can be used as
      adjuncts to improve sputum clearance in chronic obstructive pulmonary disease
      (COPD), though the evidence base is incomplete. The attitudes of physiotherapists
      towards these devices in the care of patients with COPD is unknown. In addition,
      actual use compared with the prescription of medications has not been studied.
      METHODS: We analysed English prescribing data, obtained from OpenPrescribing.net,
      for a 3-year period from 2013. In addition, we conducted an online survey of
      members of the Association of Chartered Physiotherapists in Respiratory Care
      regarding awareness of devices, thresholds for treatment and device preference.
      RESULTS: Out of a potential 3.2 million COPD patient-years of treatment between
      2013 and 2015, 422 744 patient-years of treatment with carbocisteine, at a cost
      of L73 million, were prescribed, as well as 1.1 million years treatment with
      tiotropium. In the same period, only 4989 OPEP devices were prescribed. There
      were 116 responses to the survey (12% response rate), 72% in hospital practice,
      28% based in the community. There were variations in respondents' threshold for
      treatment with sputum adjuncts in COPD, and when asked to select either the
      Acapella, Flutter or positive expiratory pressure mask, preferences were 69%, 24%
      or 6%, respectively. CONCLUSIONS: There is a 100-fold difference between use of
      carbocisteine and OPEP devices in COPD, with far fewer devices prescribed than
      are included in the phenotypes clinicians believe them to be effective in.
      Variation in physiotherapist attitudes to treatment thresholds highlights the
      need for research into the effectiveness of OPEP devices in specific patient
      phenotypes.

PMID- 29071081
TI  - Lower airways inflammation in patients with ARDS measured using endotracheal
      aspirates: a pilot study.
AB  - INTRODUCTION: Our knowledge of acute respiratory distress syndrome (ARDS)
      pathogenesis is incomplete. The goal of this pilot study is to investigate the
      feasibility of measuring lower airways inflammation in patients with ARDS using
      repeated endotracheal aspirates (ETAs). METHODS: ETAs were obtained within 24
      hours by intensive care unit admission from 25 mechanically ventilated patients
      with ARDS and 10 of them underwent a second ETA within 96 hours after the first
      sampling. In each sample, cell viability was assessed using trypan blue exclusion
      method and the total and differential cell counts were measured using Neubauer
      improved cell counting chamber and cytospins stained with Diff-Quik. RESULTS: The
      median cell viability was 89 (IQR 80-93)%, with a median total cell count of 305
      (IQR 130-1270)*103/mL and a median macrophage, neutrophil, lymphocyte and
      eosinophil count, respectively, of 19.8 (IQR 5.4-71.6)*103/mL; 279 (IQR 109
      1213)*103/mL; 0 (IQR 0-0.188)*103/mL; 0 (IQR 0-1.050)*103/mL. Eosinophil count in
      the ETA correlated with the number of blood eosinophils (r=0.4840, p=0.0142).
      Cell viability and total and differential cell counts were neither significantly
      different in the second ETA compared with the first ETA nor were unaffected by
      the presence or absence of bacteria in the blood and/or ETA, or by the ARDS
      aetiology, apart from the macrophage count which was significantly increased in
      patients with ARDS associated with acute pancreatitis compared with those
      associated with pneumonia (p=0.0143). CONCLUSIONS: ETA can be used to investigate
      the cellularity of the lower airways in patients with ARDS and it is an easy-to
      perform and non-invasive procedure. Eosinophil counts in ETA and blood are
      significantly correlated. The number of macrophages in ETA may be affected by the
      aetiology of the ARDS.

PMID- 29071084
TI  - Are within-person Numerical Rating Scale (NRS) ratings of breathlessness 'on
      average' valid in advanced disease for patients and for patients' informal
      carers?
AB  - INTRODUCTION: The Numerical Rating Scale (NRS) is frequently used to assess
      patient-reported breathlessness in both a research and clinical context. A
      subgroup of patients report average breathlessness as worse than their worst
      breathlessness in the last 24 hours (paradoxical average). The Peak/End rule
      describes how the most extreme and current breathlessness influence reported
      average. This study seeks to highlight the existence of a subpopulation who give
      'paradoxical averages using the NRS, to characterise this group and to
      investigate the explanatory relevance of the 'Peak/End' rule. METHODS: Data were
      collected within mixed method face-to-face interviews for three studies: the
      Living with Breathlessness Study and the two subprotocols of the Breathlessness
      Intervention Service phase III randomised controlled trial. Key variables from
      the three datasets were pooled (n=561), and cases where participants reported a
      paradoxical average (n=45) were identified. These were compared with non-cases
      and interview transcripts interrogated. NRS ratings of average breathlessness
      were assessed for fit to Peak/End rule. RESULTS: Patients in the paradoxical
      average group had higher Chronic Respiratory Questionnaire physical domain scores
      on average p=0.042). Peak/End rule analysis showed high positive correlation
      (Spearman's rho=0.756, p<0.001). CONCLUSIONS: The NRS requires further
      standardisation with reporting of question order and construction of scale used
      to enable informed interpretation. The application of the Peak/End rule
      demonstrates fallibility of NRS-Average as a construct as it is affected by
      current breathlessness. Measurement of breathlessness is important for both
      clinical management and research, but standardisation and transparency are
      required for meaningful results.

PMID- 29071085
TI  - Sputum colour can identify patients with neutrophilic inflammation in asthma.
AB  - INTRODUCTION: Sputum colour is associated with neutrophilic inflammation in
      chronic bronchitis and chronic obstructive pulmonary disease (COPD). Neutrophilia
      and sputum expectoration is notable in asthma, but whether sputum colour is
      associated with and predicts the presence of neutrophilic inflammation in asthma
      is unknown. The objective of the study is to assess the ability of sputum colour
      in distinguishing asthma inflammatory phenotypes. METHODS: Induced sputum samples
      collected from 271 adults with stable asthma were retrospectively assessed.
      Sputum colour was determined using the BronkoTest sputum colour chart and
      correlated to differential cell counts and CXCL-8 concentration. Neutrophilic
      inflammation was defined as an age-corrected sputum neutrophil proportion
      (>=61.6% for age 20-40 years; >=63.2% for age 40-60 and >=67.2% for age >60
      years), whereas neutrophilic bronchitis (NB) was defined as high total cell count
      (>=5.1*106 cells/mL) plus an increased age-corrected neutrophil proportion. The
      optimal cut-off for sputum colour to predict neutrophilic inflammation and NB was
      determined using receiver operator characteristic curve analysis. RESULTS: A
      sputum colour score of >=3 represented and predicted neutrophilic inflammation
      with modest accuracy (area under the curve (AUC)=0.64; p<0.001,
      specificity=78.4%, sensitivity=49.2%). Participants with a sputum colour score of
      >=3 had significantly (p<0.05) higher CXCL-8, total cells and neutrophil number
      and proportion. Sputum colour score was also positively correlated with these
      factors. Sputum colour score >=3 predicted NB with reasonably good accuracy
      (AUC=0.79, p<0.001, specificity=79.3%, sensitivity=70.7%). CONCLUSIONS: Visual
      gradation of sputum colour in asthma relates to high total cell count and
      neutrophilic inflammation. Assessment of sputum colour can identify adults with
      asthma who are likely to have NB without the need for sputum processing and
      differential cell count, which may facilitate asthma management.

PMID- 29071083
TI  - Higher BMI is associated with higher expiratory airflow normalised for lung
      volume (FEF25-75/FVC) in COPD.
AB  - INTRODUCTION: The obesity paradox in chronic obstructive pulmonary disease
      (COPD), whereby patients with higher body mass index (BMI) fare better, is poorly
      understood. Higher BMIs are associated with lower lung volumes and greater lung
      elastic recoil, a key determinant of expiratory airflow. The forced expiratory
      flow (25-75) (FEF25-75)/forced vital capacity (FVC) ratio reflects effort
      independent expiratory airflow in the context of lung volume and could be
      modulated by BMI. METHODS: We analysed data from the COPDGene study, an
      observational study of 10 192 subjects, with at least a 10 pack-year smoking
      history. Data were limited to subjects with BMI 20-40 kg/m2 (n=9222). Subjects
      were stratified according to forced expiratory volume in 1 s (FEV1) (%predicted)
      quintiles. In regression analyses and Cox proportional hazard models, we analysed
      the association between BMI, the FEF25-75/FVC ratio, the imaging phenotype, COPD
      exacerbations, hospitalisations and death. RESULTS: There was no correlation
      between BMI and FEV1(%predicted). However, a higher BMI is correlated with a
      higher FEF25-75/FVC ratio. In CT scans, a higher BMI was associated with less
      emphysema and less air trapping. In risk-adjusted models, the quintile with the
      highest FEF25-75/FVC ratio was associated with a 46% lower risk of COPD
      exacerbations (OR 0.54, p<0.001) and a 40% lower risk of death (HR 0.60, p=0.02),
      compared with the lowest quintile. BMI was not independently associated with
      these outcomes. CONCLUSIONS: A higher BMI is associated with lower lung volumes
      and higher expiratory airflows when normalised for lung volume, as quantified by
      the FEF25-75/FVC ratio. A higher FEF25-75/FVC ratio is associated with a lower
      risk of COPD exacerbations and death and might quantify functional aspects of the
      paradoxical effect of higher BMIs on COPD.

PMID- 29071086
TI  - Alcohol drinking and cigarette smoking in relation to risk of active
      tuberculosis: prospective cohort study.
AB  - INTRODUCTION: Heavy alcohol consumption increases the risk of active tuberculosis
      (TB). However, the relation between lower levels of alcohol intake and TB risk
      remains unclear. We aimed to evaluate the association between alcohol intake and
      risk of active TB and assess whether the associations were modified by smoking
      status, which is another risk factor for active TB. METHODS: The Singapore
      Chinese Health Study is a prospective cohort of 63 257 adults aged 45-74 years
      recruited from 1993 to 1998. Information on alcohol intake and smoking history
      was collected at recruitment. Active TB cases were identified via linkage with
      National TB Notification Registry. RESULTS: During a mean follow-up of 16.8
      years, 1249 incident cases of active TB were identified. Among non-smokers,
      compared with total abstinence, participants who had monthly to weekly intake of
      alcohol had reduced TB risk (HR 0.70, 95% CI 0.55 to 0.89), but this reduction in
      risk with low-dose drinking was not observed among current smokers (HR 0.96, 95%
      CI 0.77 to 1.18; p for interaction=0.02). Comparatively, drinking 2+ drinks daily
      was associated with increased TB risk among current smokers (HR 1.51, 95% CI 1.11
      to 2.05). This increased risk was not observed among non-smokers (HR 0.93, 95% CI
      0.49 to 1.77) and the interaction between alcohol intake and smoking status was
      of borderline significance (p for interaction=0.08). In joint effect, compared
      with those who neither smoked nor drank, the risk of active TB increased from
      1.82 (95% CI 1.57 to 2.10) in current smokers who were non-drinkers to 3.16 (95%
      CI 2.35 to 4.24) in current smokers who also drank 2+ drinks daily. CONCLUSION:
      While low intake of alcohol may protect against active TB among non-smokers,
      drinking 2+ drinks daily could act synergistically with smoking to increase the
      risk of active TB in current smokers.

PMID- 29071087
TI  - Glucose-lowering effects and safety of DS-8500a, a G protein-coupled receptor 119
      agonist, in Japanese patients with type 2 diabetes: results of a randomized,
      double-blind, placebo-controlled, parallel-group, multicenter, phase II study.
AB  - OBJECTIVE: DS-8500a is a novel G protein-coupled receptor 119 agonist being
      developed for the treatment of type 2 diabetes. The study objective was to assess
      the efficacy and safety of DS-8500a in Japanese patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: In this double-blind, parallel-group, phase II
      study, 99 Japanese patients with type 2 diabetes were randomized to receive
      placebo, or DS-8500a 10 mg or 75 mg once daily for 28 days. The primary efficacy
      endpoint was change in the 24-hour weighted mean glucose (WMG) from baseline (day
      -1) to day 28. Other endpoints included changes in fasting plasma glucose,
      postprandial glucose, lipids, and safety. RESULTS: The 24-hour WMG decreased
      significantly after 28 days of treatment in the 10 mg and 75 mg groups with
      placebo-subtracted least squares mean differences (95% CI) of -0.74 (-1.29 to 
      0.19) mmol/L and -1.05 (-1.59 to -0.50) mmol/L, respectively. Reductions in 24
      hour WMG in both DS-8500a groups were observed on day 14 and were greater on day
      28 than on day 14. The reductions in fasting plasma glucose and 2-hour
      postprandial glucose were significantly greater in the 75 mg DS-8500a group
      versus placebo. Total cholesterol, low-density lipoprotein cholesterol, and
      triglycerides decreased significantly; high-density lipoprotein cholesterol
      increased significantly in the 75 mg group versus placebo. Both doses of DS-8500a
      were well tolerated without significant treatment-related adverse events,
      hypoglycemia, or discontinuations due to adverse events. CONCLUSIONS: DS-8500a
      significantly improved glycemic control and lipids and was well tolerated over 28
      days of administration in Japanese patients with type 2 diabetes. TRIAL
      REGISTRATION NUMBER: NCT02222350; Post-results.

PMID- 29071088
TI  - Stair ascending-descending exercise accelerates the decrease in postprandial
      hyperglycemia more efficiently than bicycle exercise.
AB  - OBJECTIVE: Stair climbing-descending exercise (ST-EX) is a convenient method to
      increase exercise intensity. We compared the acute effect of ST-EX on lowering
      postprandial hyperglycemia with that of constant bicycle exercise (BI-EX)
      performed at the same heart rate (HR). RESEARCH DESIGN AND METHODS: Seven people
      with type 2 diabetes and seven with impaired glucose tolerance volunteered for
      this study. The step rate for ST-EX and work rate for BI-EX were individually
      determined to correspond to high-moderate to low-vigorous intensity (HR ~130
      beats per minute). For the ST-EX trial, the subjects performed 16 repetitions of
      walking down one flight of stairs followed by climbing up to the starting point
      (~8 min in duration) 90 min after consuming a test meal. For the BI-EX trial, the
      subjects performed a constant pedaling exercise for the same duration at the same
      time after the meal. RESULTS: The reduction in blood glucose (BG) level between
      90 and 105 min after a meal was significantly greater for ST-EX (-4.0+/
      0.7mmol/L) than for BI-EX (-2.7+/-0.9mmol/L). The net reduction in BG between 90
      and 105 min was also significantly greater for ST-EX (-3.2+/-0.7mmol/L) than for
      BI-EX (-2.0+/-0.6mmol/L). Serum insulin levels did not differ between the groups.
      Oxygen consumption for ST-EX was higher than that for BI-EX, but the blood
      lactate level and respiratory exchange ratio (RER) for ST-EX were lower than
      those for BI-EX. CONCLUSIONS: Compared with BI-EX performed at the same HR, ST-EX
      more rapidly decreased postprandial BG level with lower blood lactate and RER
      responses. A short bout of ST-EX may be clinically useful to acutely ameliorate
      BG levels after meals.

PMID- 29071089
TI  - Erratum: Pro-inflammatory effects of a litchi protein extract in murine RAW264.7
      macrophages.
AB  - [This corrects the article DOI: 10.1038/hortres.2016.17.].

PMID- 29071090
TI  - Significant reduction in hospital-acquired thrombosis: impact of national risk
      assessment and real-time feedback.
AB  - OBJECTIVE: Since 2010, National Health Service hospitals in England have been
      incentivised to risk assess for Venous Thromboembolism (VTE) in all adult
      patients admitted, using a national tool. We studied the impact of this, together
      with local real-time reporting of VTE events to senior clinicians, on cases of
      hospital-acquired thrombosis (HAT) diagnosed, since 2010. METHODS: This was an
      observational cohort study reviewing all cases of VTE diagnosed between January
      2010 and December 2016 in a single teaching hospital. These were matched against
      the number of patients admitted to produce crude incidence rates per thousand
      admissions. Similarly, all cases associated with inadequate thromboprophylaxis
      (TP) measures were documented over the same period. RESULTS: By the end of 2010,
      with 70% compliance with VTE risk assessment, improving to 90% (the national
      target) early in 2011, there were 217 HAT events from 103 845 admissions. In
      2016, there were 176 HAT events from 119 128 admissions, being a significant
      reduction, relative risk (RR) 0.718 (95% CI 0.589 to 0.875; p=0.001). In 2010,
      there were 50 of 217 HAT events associated with inadequate TP, falling to 7 of
      176 in 2016, also a significant reduction, RR 0.140 (95% CI 0.065 to 0.300;
      p=0.0001). CONCLUSIONS: National guidance on VTE prevention and mandatory risk
      assessment linked to local real-time reporting of VTE events are associated with
      significant reductions both in total HAT events and those associated with
      inadequate TP.

PMID- 29071091
TI  - The use of the RenalGuard system in cardiac surgery with cardiopulmonary bypass:
      a first in man prospective, observational, feasibility pilot study.
AB  - OBJECTIVES: As proof of concept, this prospective, observational study assessed
      the feasibility and early clinical outcomes of performing on-pump cardiac surgery
      with the RenalGuard system. BACKGROUND: Acute kidney injury (AKI) is reported in
      up to 30% of patients undergoing cardiac surgery and is a recognised independent
      predictor of both morbidity and mortality. Forced diuresis with the RenalGuard
      system reduces the incidence of AKI during percutaneous coronary intervention
      procedures but its use in cardiac surgery has not been explored. METHODS: Ten
      consecutive patients who were at risk of developing AKI during cardiac surgery
      were selected. The RenalGuard system was used to facilitate forced diuresis using
      weight-adjusted intravenous furosemide while maintaining neutral fluid balance by
      matched intravenous fluid replacement. This regimen was initiated preoperatively
      in all patients and continued for 6-12 hours postoperatively. Serum creatinine,
      electrolytes and need for renal replacement were documented in all patients.
      RESULTS: The RenalGuard system functioned successfully in all patients and
      facilitated high perioperative urine outputs, even when patients were placed on
      cardiopulmonary bypass (CPB). There were no incidences of significant (A)
      electrolyte imbalance, (B) changes in haemoglobin levels or (C) pulmonary oedema.
      No patients developed AKI within 36 hours of surgery despite one patient
      developing cardiac tamponade 8 hours postoperatively and one patient developing
      paralytic ileus. One patient, however, was 'electively' haemofiltered on day 2
      after developing acute right ventricular failure. The median intensive care stay
      was 1.5 (1, 5) days. CONCLUSION: The RenalGuard system can be used successfully
      in patients undergoing cardiac surgery with CPB and may reduce the incidence of
      AKI in at-risk patients. TRIAL REGISTRATION: NCT02974946; Pre-results.

PMID- 29071092
TI  - The role of microparticles in the pathogenesis of SLE: a new look at an old
      paradigm.

PMID- 29071093
TI  - Regular exercise behaviour in youth is not related to current body mass index or
      body mass index at 7-year follow-up.
AB  - OBJECTIVE: This population-based study aimed (1) to test the presence of an
      association between regular voluntary exercise behaviour (EB) that is performed
      in leisure time and body mass index (BMI) in youth and (2) to investigate the
      causal nature of this association using a longitudinal design in genetically
      informative subjects. DESIGN AND METHODS: Both EB and BMI were assessed
      repeatedly over time in 21 458 twin individuals from the Netherlands Twin
      Register (47.5% male) - first by parental report (ages 7, 10 and 12) and
      subsequently through self-report surveys (ages 14, 16 and 18). EB was quantified
      as weekly metabolic equivalent of task hours. RESULTS: Correlations over time
      were higher for BMI than for EB (r ~ 0.70 vs. r ~ 0.35) across 12 different
      follow-up periods. Cross-sectionally, regular involvement in EB was not
      associated with lower BMI in childhood and in genetically identical twin pairs
      discordant for EB; the exercising twin did not have a lower BMI than the non
      exercising twin. Longitudinally, linear and quadratic relationships between EB
      and BMI were non-significant. Changes in EB over time did not induce opposite
      changes in BMI. CONCLUSIONS: No consistent association between regular EB and BMI
      was observed from ages 7 to 18 years.

PMID- 29071094
TI  - The role of avoidance-based coping in the psychosocial functioning of weight loss
      treatment-seeking adults.
AB  - OBJECTIVE: The aim of this study was to determine the role of avoidance-based
      coping in the psychosocial functioning of weight loss treatment-seeking persons
      with obesity who report high internal disinhibition. METHODS: Participants were
      162 overweight or obese adults entering a behavioural weight loss intervention
      programme who reported high internal disinhibition at screening. We conducted
      multivariate regression analyses by using mental and physical quality of life and
      satisfaction with relationships as dependent variables and examining the
      association of demographic variables, experiential avoidance (avoidance-based
      coping) and symptoms of depression. We hypothesized that higher levels of
      experiential avoidance and symptoms of depression would be associated with poorer
      mental and physical quality of life and relationship satisfaction. Post-hoc
      analyses examined results relative to non-obese norms. RESULTS: Both experiential
      avoidance and depression were significantly and independently associated with
      each of the three psychosocial outcome measures. Individuals who were high on
      both experiential avoidance and depression scored significantly below the
      population mean for non-clinical samples on mental and physical quality of life
      and relationship satisfaction. CONCLUSION: In a sample of weight loss treatment
      seeking adults with high internal disinhibition, elevated levels of experiential
      avoidance and psychological symptoms are prevalent. Adding intervention
      components specifically designed to address unhealthy coping could results in
      improvements in overall psychosocial functioning and possibly weight loss.

PMID- 29071095
TI  - A pilot randomized controlled trial testing the effects of a routine-based
      intervention on outcomes in a behavioural weight loss programme.
AB  - BACKGROUND: Structured routines aimed at eating and sleep have been successfully
      employed in weight loss interventions for children. Although such routines are
      discussed in lifestyle modification programmes for adults, they are not a primary
      focus. PURPOSE: The purpose of this study is to determine if establishing healthy
      eating and sleep routines may improve outcomes in a behavioural weight loss (BWL)
      intervention. METHODS: Twenty-five overweight/obese participants (age = 52.4 +/-
      9.8; body mass index = 33.5 +/- 4.1) were randomly assigned to either a 4-week
      routine-based intervention (ROU) targeting regular eating and sleep or an
      education control before beginning an 18-week BWL intervention. RESULTS: Routine
      based intervention participants reported adhering to eating routines, with
      increased 'on-schedule' eating (p = 0.007) and decreased 'off-schedule' eating (p
      = 0.002) but showed no change in 'on-schedule' sleep (p = 0.74). However,
      contrary to our hypothesis, ROU participants lost less weight than controls after
      6 weeks of BWL (2.3 +/- 2.5 vs. 4.6 +/- 2.6 kg, p = 0.04) and achieved only
      modest weight loss over the full 18 weeks (ROU: 3.2 +/- 4.6 vs. education
      control: 5.8 +/- 5.7 kg, p = 0.23). CONCLUSIONS: Focusing initially on
      establishing healthy sleep and eating routines led to poorer, rather than better,
      subsequent weight loss outcomes. Further studies using a longer initial
      intervention period or focusing on only sleep or eating behaviour are needed to
      determine whether establishing routines for eating and sleep behaviours can
      enhance weight loss in adults.

PMID- 29071096
TI  - A 6-month telephone-based weight loss intervention in overweight and obese
      subjects with idiopathic intracranial hypertension.
AB  - OBJECTIVES: The purpose of this paper is to measure the change in body weight
      after a 6-month telephone-based weight loss intervention in overweight and obese
      subjects with idiopathic intracranial hypertension (IIH) and mild visual loss
      randomized to receive either acetazolamide or placebo. METHODS: One hundred sixty
      five subjects with IIH, aged 29.1 +/- 7.5 (mean +/- SD) and BMI 39.9 + 8.3 kg/m2,
      enrolled at 38 academic and private practice sites in North America, participated
      in this trial. This was a randomized, double-masked, placebo-controlled trial of
      acetazolamide in subjects with IIH and mild visual loss. All participants
      received a reduced-sodium, weight-reduction diet and a 6-month telephone-based
      weight loss intervention. Six-month changes from baseline in body weight,
      perimetric mean deviation as assessed by automated perimetry and quality of life
      using the National Eye Institute Visual Function Questionnaire 25 and the 36-item
      Short Form Health Survey were measured. RESULTS: Mean percent weight change at 6
      months was -5.9% +/- 6.7% of initial body weight overall, -3.5% +/- 5.9% in the
      placebo group and -7.8% +/- 6.8% in the acetazolamide group. Weight change was
      not associated with changes in either mean deviation or quality of life scores.
      CONCLUSION: Patients with IIH and mild visual loss assigned to either
      acetazolamide or placebo, all of whom received a 6-month telephone-based weight
      loss intervention, lost an average of 5.9% of initial body weight, consistent
      with NHLBI guidelines of 5% to 10% of body weight loss for clinically significant
      health benefit.

PMID- 29071097
TI  - Worksite nutrition supports and sugar-sweetened beverage consumption.
AB  - OBJECTIVE: This study examined the link between worksite environmental supports
      for nutrition behaviours and sugar-sweetened beverage (SSB) consumption and
      offers insight into potential intervention points for reducing SSB consumption
      and combatting overweight and obesity. METHODS: Perceived worksite supports for
      healthy nutrition and self-reported SSB consumption were analysed for 2,015
      working adults in the state of Missouri using a subset of questions from the
      Supports at Home and Work for Maintaining Energy Balance (SHOW-ME) study.
      RESULTS: Employees' use of vending facilities and the availability of water
      coolers/water bottles was significantly associated with increased SSB
      consumption, while use of cafeterias was significantly associated with decreased
      SSB consumption. Symbols or signs to identify healthy alternatives were
      significantly associated with sports drink consumption. CONCLUSIONS: This study
      supports previous work indicating the worksite as a necessary environment for
      nutrition interventions. When choices (vending and cafeteria) are provided,
      employees report making healthier decisions. For worksites without cafeterias,
      alternatives should be explored including mobile food trucks and farmer's
      markets.

PMID- 29071098
TI  - Relationships between misreported energy intake and pregnancy in the pregnancy,
      infection and nutrition study: new insights from a dynamic energy balance model.
AB  - OBJECTIVE: Providing effective dietary counselling so that pregnancy weight gain
      remains within the 2009 Institute of Medicine (IOM) guidelines requires accurate
      maternal energy intake measures. Current practice is based on self-reported
      intake that has been demonstrated unreliable. This study applies an objective
      calculation of energy intake from a validated mathematical model to identify
      characteristics of individuals more likely to misreport during pregnancy.
      METHODS: A validated maternal energy balance equation was used to calculate
      energy intake from gestational weight gain in 1,368 subjects. The difference
      between self-reported and model-predicted energy intake was tested for
      demographics, economic status, education level and maternal health status.
      RESULTS: A weight gain of 15.2 kg resulted in model-predicted intake during
      pregnancy of 2,882.97 +/-  135.71 kcal day-1, which differed from self-reported
      intake of 2,180.5 +/- 856.0 kcal day-1. The achieved weight gain exceeded the IOM
      guidelines; however, the model predicted weight gain from self-reported energy
      intake was below IOM guidelines. Higher income (p = 0.004), education (p =
      0.003), birth weight (p = 0.017), gestational diabetes (p = 0.008) and pre
      existing diabetes (p < 0.001) were associated with under-reported energy intake.
      More children living at home (p = 0.001) were associated with more accurate self
      reported intake. CONCLUSIONS: When assessing self-reported energy intake in
      pregnancy studies, birth weight, gestational diabetes status, pre-existing
      diabetes, higher income and education predict higher under-reporting. Clinicians
      providing dietary treatment recommendations during pregnancy should be aware that
      individuals with pre-existing diabetes and gestational diabetes mellitus are more
      likely to misreport their intake. Additionally, the systems model approach can be
      applied early in intervention to objectively monitor dietary compliance to
      treatment recommendations.

PMID- 29071099
TI  - Differences in weight change trajectory patterns in a publicly funded adult
      weight management centre.
AB  - OBJECTIVE: To describe differences in weight loss (WL) trajectory patterns at a
      publicly funded clinical weight management centre. METHODS: Groups with
      differences in the attainment of a 5% total body WL and percentage WL patterns
      over time were identified in 7,121 patients who attended a physician lead multi
      disciplinary clinical lifestyle weight management that predominantly focused on
      education and diet counselling. Resultant health differences were examined.
      RESULTS: Patients had 3.2 +/- 6.3%WL with 35% of patients achieving and
      maintaining a 5%WL. Half of these patients achieved the 5%WL within 6 months,
      while the other half had a more gradual approach. Another 10% achieved 5%WL, but
      regained weight after 6 months. There were seven distinct WL patterns identified:
      LargeWL (Mean WL: 21.2 +/- 8.1%; Probability of group membership (PGM): 2.4%),
      ModerateWL (15.1 +/- 5.1%WL; 5.4%PGM), SlowWL (6.7 +/- 3.2%WL; 20.1%PGM) and
      MinimalWL (2.4 +/- 2.2%WL; 34.6%PGM), WL Regain (9.4 +/- 3.5%WL; 8.2%PGM), Weight
      Stable (1.2 +/- 3.2%WL; 28.5%PGM) and Weight Gain (18.4 +/- 11.2%WG; 0.8%PGM)
      groups. Improvements in blood pressure, lipids and glucose were generally related
      to the magnitude of WL achieved more than the pattern or speed of WL.
      CONCLUSIONS: There are large differences in the absolute WL attained and the
      pattern of WL during a publicly funded weight management program. Changes in
      clinical health markers appear to be more strongly related with the absolute WL
      attained as opposed to patterns of weight change. (c) 2016 The Authors. Obesity
      Science & Practice published by John Wiley & Sons Ltd, World Obesity and The
      Obesity Society.

PMID- 29071101
TI  - Cross-sectional and prospective associations between physical activity, body mass
      index and waist circumference in children and adolescents.
AB  - OBJECTIVE: To study the cross-sectional and prospective associations between
      physical activity (PA) of different intensities, body mass index (BMI) and waist
      circumference (WC) in children and adolescents using isotemporal substitution
      modelling. METHODS: Physical activity (accelerometry), BMI and WC were assessed
      in 6- (n = 970), 9- (n = 2,423) and 15-year-olds (n = 1,544) in 2005/2006 and
      2011/2012. Participants aged 9 years in 2005/2006 were followed prospectively to
      2011/12 (age 15). Associations between PA of different intensities (light,
      moderate and vigorous), BMI and WC were examined using isotemporal substitution
      models. RESULTS: Substituting 10 min per day of sedentary time with light PA was
      associated with higher WC (0.17 to 0.29 cm, p <= 0.003)) in all age groups.
      Substituting 10 min per day of sedentary time with moderate PA was associated
      with lower WC in 6- and 9-year-olds (-0.32 to -0.47 cm, p <= 0.013)).
      Substituting 10 min per day of sedentary time with vigorous PA was associated
      with lower WC in 9- and 15-year-olds (-1.08 to -1.79 cm, p <= 0.015)).
      Associations were similar with BMI as the outcome. In prospective analyses,
      substituting sedentary time with light, moderate or vigorous PA at age 9 was not
      associated with BMI or WC at age 15. CONCLUSION: Substituting sedentary time with
      moderate PA appears favourably associated with adiposity in children, whereas
      vigorous PA may be required in adolescents. Cross-sectional associations were not
      replicated in prospective analyses.

PMID- 29071100
TI  - Effectiveness of educational and lifestyle interventions to prevent paediatric
      obesity: systematic review and meta-analyses of randomized and non-randomized
      controlled trials.
AB  - OBJECTIVE: This review and meta-analysis aim at updating a previous meta-analysis
      carried out by Waters et al. on the efficacy of interventions aimed at preventing
      childhood obesity and at identifying predictors of outcome. METHODS: Using an ad
      hoc search string, PubMed database was searched for studies assessing body mass
      index reduction associated with programmes lasting >=12 weeks in overweight and
      obese children aged 2-18 years. Studies designed for children with eating
      disorders or relevant comorbidities were excluded. Studies meeting inclusion
      criteria were classified according to patient age (<6, 6-12 and 13-18 years), and
      intervention type (physical activity, diet or both), setting (educational, family
      or both) and duration (<=1 or >1 year). The search was also extended to other
      databases. Hand-searching techniques were also applied. The Cochrane 'risk of
      bias' was applied for quality assessment. RESULTS: Seventy-two studies were meta
      analysed. Overall, the best results were achieved by programmes combining diet
      and physical activity (n = 39). With regard to the setting, programmes involving
      both school and family and lasting <=1 year were the most efficacious for 6- to
      12-year-old children (n = 26); family-based-only interventions were also
      effective in children <6 years old (n = 2), although results have to be
      interpreted cautiously because of the small number of patients enrolled and the
      high study heterogeneity. In 13- to 18-year-old patients, interventions delivered
      at school (n = 8) were substantially unsuccessful. CONCLUSIONS: Interventions for
      childhood obesity prevention should include both diet and physical activity, be
      preferentially targeted towards school age children and involve both the school
      and family setting. However, because of the important methodological limitations
      associated with currently available literature, additional studies are needed to
      draw definite conclusions.

PMID- 29071102
TI  - High intensity training in obesity: a Meta-analysis.
AB  - INTRODUCTION: High Intensity training (HIT) is a time-effective alternative to
      traditional exercise programs in adults with obesity, but the superiority in
      terms of improving cardiopulmonary fitness and weight loss has not been
      demonstrated. OBJECTIVE: to determine the effectiveness of HIT on cardiopulmonary
      fitness and body composition in adults with obesity compared to traditional (high
      volume continuous) exercise. METHODS: A systematic search of the main health
      science databases was conducted for randomized controlled trials comparing HIT
      with traditional forms of exercise in people with obesity. Eighteen studies were
      included in the meta-analysis. The (unstandardized) mean difference of each
      outcome parameters was calculated and pooled with the random effects model.
      RESULTS: HIT resulted in greater improvement of cardiopulmonary fitness (VO2max)
      (MD 1.83, 95% CI 0.70, 2.96, p<0.005; I2=31%) and a greater reduction of %body
      fat (MD -1.69, 95% CI -3.10, -0.27, p=0.02, I2=30%) compared to traditional
      exercise. Overall effect for BMI was not different between HIT and traditional
      exercise. CONCLUSION: Training at high intensity is superior to improve
      cardiopulmonary fitness and to reduce %body fat in adults with obesity compared
      to traditional exercise. Future studies are needed to design specific HIT
      programs for the obese with regard to optimal effect and long-term adherence.

PMID- 29071103
TI  - Definition of new cut-offs of BMI and waist circumference based on body
      composition and insulin resistance: differences between children, adolescents and
      adults.
AB  - OBJECTIVE: This study aims to determine associations between anthropometric
      traits, regional fat depots and insulin resistance in children, adolescents and
      adults to define new cut-offs of body mass index (BMI) or waist circumference
      (WC). DESIGN: Cross-sectional data were assessed in 433 children, adolescents and
      adults (aged: 6-60 years, BMI: 23.6 [21.0-27.7] kg m-2). Total adipose tissue
      (TAT), regional subcutaneous adipose tissue (SATtotal, SATtrunk) and visceral
      adipose tissue (VAT) were determined by whole-body magnetic resonance imaging,
      fat mass by air-displacement plethysmography. Insulin resistance was evaluated by
      homeostasis model assessment of insulin resistance (HOMA-IR). Bivariate as well
      as partial correlations and regression analyses were used. Cut-off values of BMI
      and WC related to regional fat depots and HOMA-IR were analysed by receiver
      operating characteristics curve. RESULTS: In adults, TAT, SATtotal and SATtrunk
      increased linearly with increasing BMI and WC, whereas they followed a cubic
      function in children and adolescents with a steep increase at BMI and WC >=1
      standard deviation score and VAT at WC >=2 standard deviation score. Sex
      differences were apparent in adults with women having higher masses of TAT and
      SAT and men having higher VAT. Using established BMI or WC cut-offs,
      correspondent masses of TAT, SATtotal, SATtrunk and VAT increased from childhood
      to adulthood. In all age groups, there were positive associations between BMI,
      WC, SATtrunk, VAT and HOMA-IR. When compared with normative cut-offs of BMI or
      WC, HOMA-IR-derived cut-offs of regional fat depots were lower in all age groups.
      CONCLUSIONS: Associations between BMI, WC and regional fat depots varied between
      children, adolescents, young and older adults. When compared with BMI-derived and
      WC-derived values, an insulin resistance-derived cut-off corresponded to lower
      masses of regional fat depots. Thus, established BMI and WC cut-offs are not
      appropriate to assess metabolic disturbances associated with obesity; therefore,
      new cut-offs of BMI and WC are needed for clinical practice.

PMID- 29071104
TI  - How does plate size affect estimated satiation and intake for individuals in
      normal-weight and overweight groups?
AB  - OBJECTIVE: Manipulating plate sizes could possibly introduce perceptual biases
      for judging food satiation and intake, which is thought to be related to the
      Delbeouf illusion - a visual illusion based on the perceived size of one object
      related to another. This study was to investigate whether an association exists
      between an individual's susceptibility to the plate-size-effect and their weight
      status (i.e. normal-weight versus overweight). METHODS: The study assessed the
      effect of plate size amongst normal-weight (N = 124) and overweight (N = 79) New
      Zealand Europeans. All participants were asked to rate estimated satiation (ES)
      and intake (EI) on Visual Analogue Scales for 20 food images, which comprised
      photographs of ten different dishes placed on large versus small plates. These
      responses were analysed by mixed-model ANCOVA. RESULTS: The results showed that
      the plate size had significant effects on ES (F(1, 1986) = 19.14, p < 0.001) and
      EI (F(1,1986) = 5.25; p = 0.048), with the small plate associated with higher ES
      and lower EI than the large plate. Significant differences in ES and EI were also
      evident across the weight groups (ES: F(1,1986) = 4.26, p = 0.039; EI: F(1,1986)
      = 42.22, p < 0.001), with the normal-weight group reported higher ES and lower EI
      than the overweight group. Furthermore, the weight group and the plate-size
      effect were found to be involved in a significant interaction for EI. Post-hoc
      tests showed that the plate size only had a significant effect for the normal
      weight group (p < 0.05), but not for the overweight group. CONCLUSIONS: Overall,
      the study demonstrated that the normal-weight and overweight group differed in
      their susceptibilities to the plate-size-effect (reflected by EI). This study
      revealed some potential moderators for the plate-size-effect, such as the type of
      dish, and its associated appeal and familiarity, and provided useful indications
      about the effectiveness of small plates for food reduction.

PMID- 29071106
TI  - Equivalent reductions in body weight during the Beef WISE Study: beef's role in
      weight improvement, satisfaction and energy.
AB  - OBJECTIVE: The objective of this randomized equivalence trial was to determine
      the impact of consuming lean beef as part of a high protein (HP) weight-reducing
      diet on changes in body weight, body composition and cardiometabolic health.
      METHODS: A total of 120 adults (99 female) with overweight or obesity (BMI: 35.7
      +/- 7.0 kg m-2) were randomly assigned to consume either a HP diet with >=4
      weekly servings of lean beef (B; n = 60) or a HP diet restricted in all red meats
      (NB; n = 60) during a 16-week weight loss intervention. RESULTS: Body weight was
      reduced by 7.8 +/- 5.9% in B and 7.7 +/- 5.5% in NB (p < 0.01 for both). Changes
      in percent body weight were equivalent between B and NB (mean difference: 0.06%,
      90% confidence interval: (-1.7, 1.8)). Fat mass was reduced in both groups (p <
      0.01; B: 8.0 +/- 0.6 kg, NB: 8.6 +/- 0.6 kg), while lean mass was not reduced in
      either group. Improvements in markers of cardiometabolic health (total
      cholesterol, low-density lipoprotein cholesterol, triglycerides and blood
      pressure) were not different between B and NB. CONCLUSION: Results of this study
      demonstrate that HP diets - either rich or restricted in red meat intakes - are
      effective for decreasing body weight and improving body composition and
      cardiometabolic health.

PMID- 29071107
TI  - Characteristics of adults with overweight/obesity and high internal
      disinhibition: do they fit with targets for acceptance-based interventions?
AB  - OBJECTIVE: Adults with overweight/obesity reporting high levels of internal
      disinhibition (ID) tend to do poorly in standard behavioural weight loss
      programmes. The current study sought to compare a sample of individuals with
      overweight/obesity selected on the basis of high ID with an unselected treatment
      seeking sample of adults with overweight/obesity on characteristics that might
      make acceptance-based treatments particularly appropriate for those with high ID.
      METHODS: Sample 1 included 162 treatment-seeking adults with overweight/obesity
      who were selected for high ID; sample 2 included 194 unselected treatment-seeking
      adults with overweight/obesity. First, the two samples were compared on levels of
      general and weight-related experiential avoidance, and values-consistent
      behaviour, both of which are targeted in acceptance-based treatments, and on
      other general psychological characteristics. Next, the unselected sample was
      split into two groups, those meeting criteria for high (N = 105; sample 2/high
      ID) vs. low (N = 89; sample 2/low ID) ID, and the three groups were compared on
      the same characteristics. RESULTS: Sample 1 reported higher levels of both
      general and weight-related experiential avoidance as well as less values
      consistent behaviour than sample 2. They reported greater psychological
      impairment in quality of life, depression and anxiety. Within sample 2, 54% met
      the criteria for high ID. Both sample 1 and sample 2/high ID reported higher
      levels of experiential avoidance and less values-consistent behaviour than did
      the sample 2/low ID. The two high ID samples also reported greater psychological
      impairment in quality of life, depression and anxiety than sample 2/low ID.
      CONCLUSIONS: Adults with overweight/obesity who report high levels of ID were
      characterized by higher levels of experiential avoidance, lower levels of values
      consistent behaviour, and more psychosocial impairment as compared with other
      adults with overweight/obesity. As these are important targets of acceptance
      based approaches, this subgroup may benefit from the integration of such
      approaches into behavioural weight loss programmes.

PMID- 29071105
TI  - Cognitive effects of a 30-min aerobic exercise bout on adults with
      overweight/obesity and type 2 diabetes.
AB  - BACKGROUND: Several studies document reliable brain health benefits of acute
      exercise bouts. However, no prior studies have explored such effects among those
      living with co-morbid overweight/obesity and type 2 diabetes (T2DM), both of
      which are conditions associated with cognitive performance decrements. PURPOSE:
      To examine the impact of a 30-min bout of moderate-intensity aerobic exercise on
      executive function among adults with overweight/obesity and T2DM, employing a
      widely used experimental paradigm. METHODS: Thirty adults with overweight/obesity
      and T2DM were randomly assigned to moderate (30% maximal heart rate reserve) and
      minimal (r.p.m. 30-50; work load 5) intensity aerobic exercise. Pre-exercise to
      post-exercise changes in Stroop interference and Go/No-Go scores were compared
      across conditions. RESULTS: Primary analyses revealed no overall effect of
      exercise condition on changes in Stroop or Go/No-Go performance. Post-hoc
      moderation analyses indicated that Stroop interference scores were reduced,
      following moderate exercise among female participants and among those who were
      more physically active. CONCLUSION: The current study revealed no reliable
      benefit of acute aerobic exercise for overweight and obese individuals living
      with T2DM overall. There may be limited benefits for women and more and active
      subgroups, but the precise nature of such benefits remains unclear.

PMID- 29071108
TI  - The effect of bariatric surgery on serum 25-OH vitamin D levels: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Concerns have emerged about post-operative decreases in calcium and
      vitamin D following bariatric surgery. This review explores changes in metabolic
      bone health in persons with obesity undergoing gastric bypass surgery compared to
      non-surgical controls, providing an updated and comprehensive perspective on the
      literature. METHODS: An electronic search was conducted in MEDLINE, Pubmed,
      EMBASE and Cochrane databases to 8 November 2016. Eligible trials included
      randomized controlled trials or controlled observational studies of patients who
      have undergone laparoscopic gastric bypass surgery. Statistical analysis was
      carried out using the Cochrane Collaboration Review Manager (RevMan 5.0), and a
      random effects model was implemented. Outcomes were expressed as weighted mean
      difference (WMD). The primary outcome examined was change in 25-OH-D levels at 12
      months post surgery, and secondary outcomes included change in bone mineral
      density (BMD) measurements at 12 months post surgery at the lumbar spine (LS) and
      total hip (TH). RESULTS: At 12 months, there was no significant difference in 25
      OH vitamin D in the surgical group compared to controls (WMD = 6.79%; 95% CI: 
      9.01, 22.59; p = 0.40; I2 = 68%). There was no statistically significant
      difference between fracture risk in the surgical population compared to controls
      (RR = 1.24; 95% CI: 0.99, 1.56; p = 0.06; I2 = 0%). A significant BMD reduction
      was however shown at the TH (WMD, -7.33%, 95% CI = -8.70 to -5.97, p < .001, I2 =
      0%), and a trend towards decline was observed at the LS (WMD, -1.73%, 95% CI = 
      3.56 to 0.11, p = 0.06, I2 = 0%). Changes at 24 months for applicable outcomes
      were similar to the results at 12 months. CONCLUSIONS: Bariatric surgery may
      compromise metabolic bone health, but the paucity of high-quality literature
      limits conclusions.

PMID- 29071109
TI  - Association of built environment characteristics with adiposity and glycaemic
      measures.
AB  - OBJECTIVE: This study examined the cross-sectional and longitudinal relationships
      of built environment characteristics with adiposity and glycaemic measures.
      METHOD: Longitudinal study sample consisted of 4,010 Framingham Heart Study
      Offspring (baseline: 1998-2001; follow-up: 2005-2008) and Generation Three
      (baseline: 2002-2005; follow-up: 2008-2011) participants (54.8% women, baseline
      mean age 48.6 years). Built environment characteristics (intersection density,
      greenspace, recreation land and food stores) at baseline were collected.
      Adiposity and glycaemic measures (body mass index [BMI], waist circumference,
      abdominal subcutaneous and visceral adipose tissue, and fasting plasma glucose)
      at baseline and changes during 6.4-year follow-up were measured. RESULTS: In
      cross-sectional models, higher intersection density and food store density (total
      food stores, fast food restaurants and supermarkets) were linearly associated
      with higher BMI (all p < 0.05). Higher greenspace was associated with lower BMI,
      waist circumference, fasting plasma glucose, prevalent obesity and prevalent
      diabetes (all p < 0.05). Longitudinally, higher intersection density and food
      store density, and lower greenspace were associated with smaller increases in
      abdominal visceral adipose tissue (all p < 0.05). Higher densities of
      intersections, fast food restaurants and supermarkets were associated with
      smaller increases in fasting plasma glucose (all p < 0.05). CONCLUSIONS:
      Collectively, built environment characteristics are associated with adiposity and
      glycaemic traits, suggesting the potential mechanisms by which built environment
      influences cardiometabolic health.

PMID- 29071110
TI  - Real-world weight change among patients treated with glucagon-like peptide-1
      receptor agonist, dipeptidyl peptidase-4 inhibitor and sulfonylureas for type 2
      diabetes and the influence of medication adherence.
AB  - AIMS: The study aims to examine real-world weight change and the role of
      medication adherence among patients with type 2 diabetes who initiated one of
      three drug classes: glucagon-like peptide-1 receptor agonist (GLP-1RA),
      dipeptidyl peptidase-4 inhibitor (DPP4) and sulfonylureas (SUs). MATERIALS AND
      METHODS: A cohort of patients initiating one of the three drug classes was
      selected from a large US database of integrated electronic medical record and
      administrative claims. Adherence was defined as per cent of days covered >=80%
      during the year following drug initiation. Weight change was calculated from drug
      initiation (-180, +30 d) to 1 year (+/-90 d) later. Multivariate regression
      controlled for baseline differences between adherent and poorly adherent patients
      and the addition of another drug class during follow-up. RESULTS: The study
      included 833 GLP-1RA, 2,272 DPP4 and 2,713 SU patients who contributed 2,279,
      6,602 and 7,429 observations respectively. Patients initiating a GLP-1RA achieved
      the largest weight change (-2.46 kg of GLP-1RA, -1.26 kg of DPP4 and 0.18 kg of
      SU, P < 0.01). Adherent GLP-1 patients lost 1.73 kg more than poorly adherent
      patients, and adherent SU patients gained 1.11 kg more than poorly adherent
      patients (all P < 0.01). Adherent and poorly adherent DPP4 patients experienced
      approximately the same amount of weight loss. CONCLUSIONS: Medication adherence
      can mediate observed weight loss in patients treated with a GLP1-RA or weight
      gain in those treated with an SU. Medication adherence was low in a real-world
      population, particularly for GLP-1RA, which displayed the strongest weight loss
      benefit. Because recent American Diabetes Association guidelines recommend
      selecting drug therapies that have a weight loss or weight neutral effect for the
      management of type 2 diabetes patients, patients should be encouraged to enhance
      their adherence to benefit the most from therapies that have weight loss
      properties.

PMID- 29071111
TI  - Impact of pioglitazone and bradykinin type 1 receptor antagonist on type 2
      diabetes in high-fat diet-fed C57BL/6J mice.
AB  - AIM: Type 2 diabetes (T2D) is a major complication of obesity and a leading cause
      of morbidity and mortality. Antagonizing bradykinin type 1 receptor (B1R)
      improved body and tissue fat mass and reversed vascular and adipose tissue
      inflammation in a rat model of insulin resistance. This study aimed at evaluating
      further the role of B1R in a mouse model of T2D by comparing the antidiabetic and
      anti-inflammatory effects of the B1R antagonist SSR240612 (SSR) in adipose tissue
      with those of pioglitazone (TZD), an activator of peroxisome proliferator
      activated receptor gamma. METHODS: C57BL/6J mice were fed with high-fat diet
      (HFD) or standard diet (control) for 20 weeks. Yet, during the last 4 weeks, HFD
      fed mice were administered SSR and TZD (10 mg kg-1 d-1 each) as monotherapy or
      combined therapy subcutaneously. The impact of treatments was measured on
      metabolic hormones levels (ELISA), adipose tissue inflammatory status and the
      expression of candidate genes involved in T2D (quantitative real-time polymerase
      chain reaction and western blot). RESULTS: SSR240612 and TZD treatments improved
      hyperglycaemia, hyperinsulinaemia, insulin resistance, adipose tissue
      inflammation (expression of B1R, chemokine ligand 2, F4/80 and tumour necrosis
      factor) and modulated adipogenesis (peroxisome proliferator-activated receptor
      gamma, adipocytes' protein 2 and CD40 expressions) in HFD-fed mice. Yet, SSR was
      more effective than TZD to reduce visceral fat mass and resistin. TZD/SSR
      combined treatment had an additive effect to improve insulin sensitivity and
      glucose intolerance. CONCLUSION: Bradykinin type 1 receptor antagonism could
      represent a promising therapeutic tool in combination with TZD for the treatment
      of T2D, obesity and insulin resistance.

PMID- 29071112
TI  - The first prospective injury audit of League of Ireland footballers.
AB  - OBJECTIVES: Football has the highest sports participation (10.6%) in Ireland
      ahead of its Gaelic counterpart (3.9%). Research into injury incidence and
      patterns in Irish football is non-existent. The aim of this study was to conduct
      a prospective injury audit of League of Ireland (semiprofessional) footballers
      during the 2014 season (8 months, 28 games). METHODS: A total of 140
      semiprofessional League of Ireland footballers were prospectively followed
      between March and November 2014. Data were collected in accordance with the
      international consensus on football injury epidemiology. RESULTS: The injury rate
      was 9.2/1000 hour exposure to football (95% CI 6.2 to 12.9, p<0.05). Players were
      at a higher risk of injury during a match compared with training (23.1 (95% CI
      15.2 to 31.3) vs 4.8 (95% CI 2.2 to 7.7)/1000 hours, p<0.05). Injuries were most
      common during non-contact activity (54.6%), mainly running (30.9%), and occurred
      almost three times more often in the second half (56% vs 21%, p<05). Strains
      (50.1%) and sprains (20.3%) were the most common injury types, and the thigh
      region was injured most often (28.3%). CONCLUSIONS: The prevalence of injury in
      League of Ireland football is similar to that of European professional football,
      although the incidence of injury is higher. The incidence of injury is in line
      with that of Dutch amateur football.

PMID- 29071113
TI  - Introducing the National Institute for Sports Medicine in Hungary: a complex
      sports medical healthcare and screening system.
AB  - The Hungarian National Institute for Sports Medicine (NISM) was founded in 1952
      to provide medical coverage for national teams, screening and periodic health
      evaluation (PHE) for all Hungarian athletes. The system of 'all in one and ASAP'
      evolved by now to a specific state-funded healthcare provider with complex sports
      medical and sport-related services available for athletes. The NISM created a
      countrywide network to make health clearance available for all athletes close to
      their place of residency. This centralised system guarantees the uniformity and
      financial independence of the network, as it is directly financed by the
      government and free for every competitive athlete. Thus, it leaves no chance for
      conflict of interest in evaluating athletes' eligibility. In 2013, NISM
      established an online registry for preparticipation screening and PHE. This made
      the registry available for sports physicians and certain data for both sports
      physicians and athletes themselves. Furthermore, NISM created a nationwide,
      centrally coordinated, out of turn care with central coordination for elite
      athletes nationwide. Outpatient and inpatient clinics of NISM provide sports
      specific care. Most of the minimally invasive techniques used at the Department
      of Sports Surgery are applied only here in the country. The medical staff of NISM
      has special experience in Sports Medicine and sport-related conditions. All tasks
      are managed within the same system, within institutional frames by professionals
      at Sports Medicine, which guarantees institutional expertise, competence and
      responsibility. Our aim is to introduce the complex system, the services and the
      recent achievements of the Hungarian NISM.

PMID- 29071114
TI  - Cracking the code for maintaining quality training in Olympic distance triathlon:
      lessons learnt from a squad of elite Scandinavian athletes.
AB  - OBJECTIVE: High-quality training is a key determinant of performance in the
      Olympic distance triathlon and is potentially influenced by a unique array of
      context-specific biopsychosocial factors. Our objective was to explore and
      describe these factors among squad members of a university-based, elite Olympic
      distance triathlete developmental programme. METHOD: A qualitative investigation
      using a visual communication tool-assisted focus group and longitudinal
      semistructured individual interviews was conducted. Responses were solicited from
      the University of Southern Denmark's elite triathlon team (n=8), and inductive
      coding from the focus group formed the basis of questions for the two rounds of
      individual interviews 11 months apart. All interviews were transcribed verbatim
      and then analysed thematically. RESULTS: Seventeen context-relevant factors were
      identified and 10 themes emerged, these being 'the cold weather ritual',
      'digestive system conditioning', 'the curse of the night owl', 'the strings
      attached to sponsorship', 'my coach-my rock', 'mood maintenance', 'the
      asynchronous training rhythm', 'psychological slavery', 'the legacy of the
      asphalt tattoo' and 'the tension of family and friends'. CONCLUSIONS: By
      reflecting on their personal training vortex, elite triathletes were able to
      provide context-relevant insights into the maintenance of training quality over
      the course of a competitive season. Further research is required to elucidate
      whether and how biopsycholosocial factors can be modified to optimise the
      achievement of training goals.

PMID- 29071115
TI  - Acceptability and perceptions of end-users towards an online sports-health
      surveillance system.
AB  - AIM: To describe the acceptability and the perceptions of athletes and staff
      members (ie, end-users) towards an online sports-health surveillance system.
      METHODS: A pilot study with a mixed-methods approach was pursued. Descriptive
      analysis was conducted to present the adherence of judo (n=34), swimming (n=21)
      and volleyball (n=14) athletes to an online registration of their sport exposure
      and any health complaints between April 2014 and January 2015. End-users'
      perceptions towards the system were investigated qualitatively with
      semistructured interviews (n=21). Qualitative analysis was based on the constant
      comparative method using principles of the grounded theory. RESULTS: The response
      rates of judo, swimming and volleyball athletes were 50% (SD 23), 61% (SD 27) and
      56% (SD 25), respectively. Most athletes found it simple to register their sport
      exposure and health complaints online; however, personal communication was still
      preferred for this purpose. The system facilitated the communication between
      medical and trainer staff, who were able to identify in the system reports health
      complaints from athletes that were not necessarily communicated face-to-face.
      Therefore, staff members reported that they were able to intervene earlier to
      prevent minor health complaints from becoming severe health problems. However,
      staff members expected higher adherence of athletes to the online follow-ups, and
      athletes expected to receive feedback on their inputs to the system. CONCLUSION:
      An online system can be used in sporting settings complementary to regular
      strategies for monitoring athletes' health. However, providing feedback on
      athletes' inputs is important to maintain their adherence to such an online
      system.

PMID- 29071116
TI  - High-intensity exercise training does not influence body weight but improves
      lipid oxidation in obese adults: a 6-week RCT.
AB  - OBJECTIVES: This study examined the effects of 6 weeks of high-intensity training
      (HIT) on lipid oxidation (LO) rates during incremental exercises in obese adults.
      METHODS: Twenty-four obese adults were randomised into a no-exercise control
      group (n=12; body mass index=33.3 (4.8) kg.m-2) and a HIT group (18 sessions of
      6*6 s of supramaximal cycling and 2 min passive intervals; n=12; body mass
      index=33.2 (2.8)kg.m-2). The percentage of LO contribution was computed at rest
      and for all workloads (25, 50, 75, 100 and 125 W) in both groups before and after
      training via a graded maximal cycling test. RESULTS: After training, the HIT
      group showed significantly higher LO at rest and at 25, 50 and 75 W compared with
      baseline (p<0.01) and the control group (p<0.01). Moreover, for the training
      group, the homoeostasis model assessment of insulin resistance (HOMA-IR) index
      decreased significantly from the baseline value (p<0.01) and the control group
      value (p<0.01). The increases in LO observed at rest and stages 25, 50 and 75 W
      were positively correlated with the declines in the HOMA-IR index (r=0.87,
      r=0.83, r=0.91 and r=0.88; p<0.01). CONCLUSION: In obese adults, HIT increased
      lipid contributions to energy release at rest and in response to incremental
      exercise, while there were no changes in participants' aerobic capacity. This
      supports the hypothesis that metabolic changes rather than improved aerobic
      capacity are important to improve LO. TRIAL REGISTRATION NUMBER: ISRCTN66508384.
      Stage: post-results.

PMID- 29071117
TI  - Variants of genes implicated in type 1 interferon pathway and B-cell activation
      modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis.
AB  - BACKGROUND: The type 1 interferon (IFN) pathway has been identified to
      potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA),
      which suggests the contribution of type 1 IFN pathway genes such as IFN
      regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal
      transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our
      objective was to study functional variants of these IFN pathway genes as
      predictors of the European League Against Rheumatism (EULAR) response to RTX for
      RA at week 24 (W24). METHODS: Logistic regression analysis with a stepwise
      multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in
      28 joints with C reactive protein) in 115 patients from the SMART randomised
      studywas used to analyse the association between the candidate variants and W24
      EULAR response. Because the variant TNFSF13B rs9514828 was previously found
      associated with RTX response in the same population, it was included in the
      analysis. RESULTS: The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B
      rs9514828 was strongly associated with good/moderate EULAR response to RTX at
      W24: p=9.34*10-6, OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91%
      and negative predictive value 54%. CONCLUSION: Our results support the
      contribution of the IRF5, SPP1 and TNFSF13B genotypic combination in the response
      to RTX for RA at W24.

PMID- 29071118
TI  - Influence of aromatase inhibitors therapy on the occurrence of rheumatoid
      arthritis in women with breast cancer: results from a large population-based
      study of the Italian Society for Rheumatology.
AB  - OBJECTIVES: The purpose of this study was to evaluate the risk of developing
      rheumatoid arthritis (RA) in a population of patients with breast cancer treated
      with aromatase inhibitors (AIs) compared with tamoxifen. METHODS: Data were
      collected from the administrative healthcare database of Lombardy Region, Italy,
      from 2004 to 2013. This study follows a nested cohort design, including women
      with a diagnosis of breast cancer starting treatment with tamoxifen, anastrozole,
      exemestane or letrozole. The risk of RA related to the prescription of the
      different drugs was estimated by survival models for competing risks and the
      results are presented as hazard ratios (HRs) and 95% confidence intervals (95%
      CI), adjusted for age and cancer severity. RESULTS: Out of total 10 493 women
      with breast cancer with a median (IQR) age of 66 (57-74), 7533 (71.8%) started an
      active treatment with AIs or tamoxifen. In this subgroup a total of 113 new cases
      of RA developed during the 26 105.9 person-year of 10 186 exposure periods,
      including time varying exposures in the same patient. Using tamoxifen as
      reference category, AIs therapy was associated with an increased risk of RA
      (adjusted HR 1.62 (95%1.03-2.56)), in particular in patients receiving
      anastrozole, even after adjusting for age and level of neoplasia: (adjusted HR
      1.75 (95%1.07-2.86)). CONCLUSIONS: In a large population-based sample of women
      with breast cancer, exposure to AIs compared with tamoxifen is associated with a
      significantly increased risk of RA, which is not influenced by the cancer
      severity and the relationship of age with indication to specific drugs.

PMID- 29071119
TI  - Switching biological disease-modifying antirheumatic drugs in patients with axial
      spondyloarthritis: results from a systematic literature review.
AB  - OBJECTIVES: First, to investigate if switching biological disease-modifying
      antirheumatic drugs (bDMARDs) after the failure to prior bDMARD is efficacious in
      patients with axial spondyloarthritis (axSpA). Second, to evaluate the influence
      on this efficacy of (1) the reason to discontinue prior tumour necrosis factor
      inhibitor (TNFi), (2) changing the type of TNFi and (3) changing the target.
      METHODS: A systematic literature review until January 2017 was performed using
      Medline, EMBASE and Cochrane databases. Longitudinal studies assessing clinical
      response after switching bDMARDs in patients with axSpA were analysed. RESULTS:
      In total, 9 studies out of 1862 retrieved citations were included. Overall, the
      level of evidence was poor. In these studies, all patients received a TNFi as
      first bDMARD, 1956 patients switched to a second bDMARD (97% TNFi and 3%
      interleukin-17 inhibitors (IL-17i)) and 170 to a third bDMARD (all TNFi).
      Clinical response (Bath Ankylosing Spondylitis Disease Activity Index 50) after a
      second TNFi was achieved by 25%-56% of patients compared with 50%-72% after the
      first TNFi. Also, 47% of patients switching to IL-17i after a TNFi responded
      (Assessment of SpondyloArthritis international Society 40) compared with 66% in
      those who received IL-17i as first line. The response after switching was not
      influenced by the reason to discontinue, type of prior TNFi or changing the
      target. CONCLUSIONS: In patients with axSpA, switching to a second bDMARD (a TNFi
      or IL-17i) after prior TNFi is efficacious. Nevertheless, the clinical response
      is lower than the observed in patients naive to bDMARD. So far, the reason to
      discontinue prior bDMARD or the type of bDMARD has not been identified as
      predictor of response. Published evidence for switching to a third bDMARD is
      lacking.

PMID- 29071120
TI  - Safety and efficacy of baricitinib in elderly patients with rheumatoid arthritis.

PMID- 29071121
TI  - Binding to RNA regulates Set1 function.
AB  - The Set1 family of histone H3 lysine 4 (H3K4) methyltransferases is highly
      conserved from yeast to human. Here we show that the Set1 complex (Set1C)
      directly binds RNA in vitro through the regions that comprise the double RNA
      recognition motifs (dRRM) and N-SET domain within Set1 and its subunit Spp1. To
      investigate the functional relevance of RNA binding, we performed UV RNA
      crosslinking (CRAC) for Set1 and RNA polymerase II in parallel with ChIP-seq
      experiments. Set1 binds nascent transcripts through its dRRM. RNA binding is
      important to define the appropriate topology of Set1C distribution along
      transcription units and correlates with the efficient deposition of the H3K4me3
      mark. In addition, we uncovered that Set1 binds to different classes of RNAs to
      levels that largely exceed the levels of binding to the general population of
      transcripts, suggesting the Set1 persists on these RNAs after transcription. This
      class includes RNAs derived from SET1, Ty1 retrotransposons, specific
      transcription factors genes and snRNAs (small nuclear RNAs). We propose that Set1
      modulates adaptive responses, as exemplified by the post-transcriptional
      inhibition of Ty1 retrotransposition.

PMID- 29071123
TI  - Treatment of scapholunate ligament injury: Current concepts.
AB  - Injuries to the scapholunate joint are the most common cause of carpal
      instability.An isolated injury to the scapholunate ligament may progress to
      abnormal joint mechanics and degenerative cartilage changes.Treatment for
      scapholunate instability is aimed at arresting the degenerative process by
      restoring ligament continuity and normalising carpal kinematics.Early
      arthroscopic diagnosis of scapholunate injury is mandatory for establishing the
      prognosis of the injury, as a proper ligament repair is recommended within four
      to six weeks after trauma.In this review, anatomy, diagnosis and treatment of
      scapholunate ligament injury and carpal instability are discussed.
      Recommendations for treatment based on the stage and classification of injury and
      the degree of instability and arthritic changes are proposed. Cite this article:
      EFORT Open Rev 2017;2:382-393. DOI: 10.1302/2058-5241.2.170016.

PMID- 29071122
TI  - Diagnostic algorithm, prognostic factors and surgical treatment of metastatic
      cancer diseases of the long bones and spine.
AB  - Oncological management of skeletal metastases has changed dramatically in the
      last few decades. A significant number of patients survive for many years with
      their metastases.Surgeons are more active and the technical repertoire is
      broader, from plates to intramedullary devices to (tumour) endoprostheses.The
      philosophy of treatment should be different in the case of a trauma-related
      fracture and a pathological fracture. A proper algorithm for establishing a
      diagnosis and evaluation of prognostic factors helps in planning the surgical
      intervention.The aim of palliative surgery is usually to eliminate pain and to
      allow the patient to regain his/her mobility as well as to improve the quality of
      life through minimally invasive techniques using life-long durable devices.In a
      selected group of patients with an oncologically controlled primary tumour site
      and a solitary bone metastasis with positive prognostic factors, which meet the
      criteria for radical excision (approximately 10% to 15% of the cases), a
      promising three to five years of survival may be achieved, especially in cases of
      metastases from breast and kidney cancer.Spinal metastases require meticulous
      evaluation because decisions on treatment mostly depend on the tumour type,
      segmental stability, the patient's symptoms and general state of health.Advanced
      radiotherapy combined with minimally invasive surgical techniques (minimally
      invasive stabilisation and separation surgery) provides durable local control
      with a low complication rate in a number of patients. Cite this article: EFORT
      Open Rev 2017;2:372-381.

PMID- 29071126
TI  - The ESMO position paper on biosimilars in oncology: enhancing the provision of
      accurate education and information.

PMID- 29071124
TI  - Management of anticoagulation in hip fractures: A pragmatic approach.
AB  - Hip fractures are common and increasing with an ageing population. In the United
      Kingdom, the national guidelines recommend operative intervention within 36 hours
      of diagnosis. However, long-term anticoagulant treatment is frequently
      encountered in these patients which can delay surgical intervention. Despite
      this, there are no set national standards for management of drug-induced
      coagulopathy pre-operatively in the context of hip fractures.The aim of this
      study was to evaluate the management protocols available in the current
      literature for the commonly encountered coagulopathy-inducing agents.We reviewed
      the current literature, identified the reversal agents used in coagulopathy
      management and assessed the evidence to determine the optimal timing, doses and
      routes of administration.Warfarin and other vitamin K antagonists (VKA) can be
      reversed effectively using vitamin K with a dose in the range of 2 mg to 10 mg
      intravenously to correct coagulopathy.The role of fresh frozen plasma is not
      clear from the current evidence while prothrombin complex remains a reliable and
      safe method for immediate reversal of VKA-induced coagulopathy in hip fracture
      surgery or failed vitamin K treatment reversal.The literature suggests that
      surgery should not be delayed in patients on classical antiplatelet medications
      (aspirin or clopidogrel), but spinal or regional anaesthetic methods should be
      avoided for the latter. However, evidence regarding the use of more novel
      antiplatelet medications (e.g. ticagrelor) and direct oral anticoagulants remains
      a largely unexplored area in the context of hip fracture surgery. We suggest
      treatment protocols based on best available evidence and guidance from allied
      specialties.Hip fracture surgery presents a common management dilemma where semi
      urgent surgery is required. In this article, we advocate an evidence-based
      algorithm as a guide for managing these anticoagulated patients. Cite this
      article: EFORT Open Rev 2017;2:394-402. DOI: 10.1302/2058-5241.2.160083.

PMID- 29071125
TI  - Management of syndesmotic injuries of the ankle.
AB  - Injuries to the tibioperoneal syndesmosis are more frequent than previously
      thought and their treatment is essential for the stability of the ankle
      mortise.Recognition of these lesions is essential to avoid long-term
      morbidity.Diagnosis often requires complete history, physical examination, weight
      bearing radiographs and MRI.Treatment-oriented classification is mandatory.It is
      recommended that acute stable injuries are treated conservatively and unstable
      injuries surgically by syndesmotic screw fixation, suture-button dynamic fixation
      or direct repair of the anterior inferior tibiofibular ligament.Subacute injuries
      may require ligamentoplasty and chronic lesions are best treated by syndesmotic
      fusion.However, knowledge about syndesmotic injuries is still limited as
      recommendations for surgical treatment are only based on level IV and V evidence.
      Cite this article: EFORT Open Rev 2017;2:403-409. DOI: 10.1302/2058
      5241.2.160084.

PMID- 29071127
TI  - Is the sustainable development goal target for financial risk protection in
      health realistic?
AB  - BACKGROUND: Setting Millennium Development Goals and Sustainable Development
      Goals for health has largely focused on defining specific targets of mortality
      and morbidity reduction over given time periods. Yet, less attention has been
      devoted to setting targets for the systemic determinants of health delivery, such
      as access and financial risk protection (FRP)-prevention of medical
      impoverishment. We examined candidate targets for FRP among low and middle-income
      countries by 2040. METHODS: We used a data set on estimates of incidence of
      catastrophic health expenditure (CHE)-medical expenditure exceeding 40% of
      household capacity to pay-among 110 countries over 1995-2007, augmented by
      estimates of the percentage of out-of-pocket expenditure out of total health
      expenditure (OOPEXP), the share of health expenditure as a percentage of gross
      domestic product (HEXGDP) and the gross domestic product per capita (GDPC). Using
      a simple model and 2040 estimates for OOPEXP, HEXGDP and GDPC from the World
      Bank, the International Monetary Fund and the Institute for Health Metrics and
      Evaluation, we projected CHE incidence by 2040 for four country income groups.
      RESULTS: We predicted that the 2040 incidence of CHE among households would be:
      2.13% (Uncertainty interval: 0.60-6.87) among low-income countries, 1.15% (0.32
      3.81) among lower-middle-income countries and 0.65% (0.18-2.21) among upper
      middle-income countries. By 2040, the probability of achieving CHE <1.00% would
      be: 0.1 for low-income countries, 0.4 for lower-middle-income countries and 0.7
      for upper-middle-income countries; for CHE <0.50%, it would be 0 for low-income
      countries, 0.1 for lower-middle-income countries and 0.3 for upper-middle-income
      countries. CONCLUSIONS: Historical trends of CHE rates can help define post-2015
      targets for FRP. The projected achievements suggest that elimination of medical
      impoverishment will not be achieved by 2040 and that countries must urgently
      enact dramatic changes in policy to ensure FRP to their populations.

PMID- 29071128
TI  - Introducing visual participatory methods to develop local knowledge on HIV in
      rural South Africa.
AB  - INTRODUCTION: South Africa is a country faced with complex health and social
      inequalities, in which HIV/AIDS has had devastating impacts. The study aimed to
      gain insights into the perspectives of rural communities on HIV-related
      mortality. METHODS: A participatory action research (PAR) process, inclusive of a
      visual participatory method (Photovoice), was initiated to elicit and organise
      local knowledge and to identify priorities for action in a rural subdistrict
      underpinned by the Agincourt Health and Socio-Demographic Surveillance System
      (HDSS). We convened three village-based discussion groups, presented HDSS data on
      HIV-related mortality, elicited subjective perspectives on HIV/AIDS, systematised
      these into collective accounts and identified priorities for action. Framework
      analysis was performed on narrative and visual data, and practice theory was used
      to interpret the findings. FINDINGS: A range of social and health systems factors
      were identified as causes and contributors of HIV mortality. These included
      alcohol use/abuse, gender inequalities, stigma around disclosure of HIV status,
      problems with informal care, poor sanitation, harmful traditional practices,
      delays in treatment, problems with medications and problematic staff-patient
      relationships. To address these issues, developing youth facilities in
      communities, improving employment opportunities, timely treatment and extending
      community outreach for health education and health promotion were identified.
      DISCUSSION: Addressing social practices of blame, stigma and mistrust around HIV
      related mortality may be a useful focus for policy and planning. Research that
      engages communities and authorities to coproduce evidence can capture these
      practices, improve communication and build trust. CONCLUSION: Actions to reduce
      HIV should go beyond individual agency and structural forces to focus on how
      social practices embody these elements. Initiating PAR inclusive of visual
      methods can build shared understandings of disease burdens in social and health
      systems contexts. This can develop shared accountability and improve staff
      patient relationships, which, over time, may address the issues identified, here
      related to stigma and blame.

PMID- 29071129
TI  - Facilitating access to surgical care through a decentralised case-finding
      strategy: experience in Madagascar.
AB  - Over two-thirds of the world's population lack access to surgical care. Non
      governmental organisation's providing free surgeries may overcome financial
      barriers, but other barriers to care still exist. This analysis paper discusses
      two different case-finding strategies in Madagascar that aimed to increase the
      proportion of poor patients, women and those for whom multiple barriers to care
      exist. From October 2014 to June 2015, we used a centralised selection strategy,
      aiming to find 70% of patients from the port city, Toamasina, and 30% from the
      national capital and two remote cities. From August 2015 to June 2016, a
      decentralised strategy was used, aiming to find 30% of patients from Toamasina
      and 70% from 11 remote locations, including the capital. Demographic information
      and self-reported barriers to care were collected. Wealth quintile was calculated
      for each patient using a combination of participant responses to asset-related
      and demographic questions, and publicly available data. A total of 2971 patients
      were assessed. The change from centralised to decentralised selection resulted in
      significantly poorer patients undergoing surgery. All reported barriers to prior
      care, except for lack of transportation, were significantly more likely to be
      identified in the decentralised group. Patients who identified multiple barriers
      to prior surgical care were less likely to be from the richest quintile (p=0.037)
      and more likely to be in the decentralised group (p=0.046). Our country-specific
      analysis shows that decentralised patient selection strategies may be used to
      overcome barriers to care and allow patients in greatest need to access surgical
      care.

PMID- 29071130
TI  - Scaling up quality improvement intervention for perinatal care in Nepal
      (NePeriQIP); study protocol of a cluster randomised trial.
AB  - INTRODUCTION: Nepal Perinatal Quality Improvement Project (NePeriQIP) intends to
      scale up a quality improvement (QI) intervention for perinatal care according to
      WHO/National guidelines in hospitals of Nepal using the existing health system
      structures. The intervention builds on previous research on the implementation of
      Helping Babies Breathe-quality improvement cycle in a tertiary healthcare setting
      in Nepal. The objective of this study is to evaluate the effect of this scaled-up
      intervention on perinatal health outcomes. METHODS/DESIGN: Cluster-randomised
      controlled trial using a stepped wedged design with 3 months delay between wedges
      will be conducted in 12 public hospitals with a total annual delivery rate of 60
      000. Each wedge will consist of 3 hospitals. Impact will be evaluated on
      intrapartum-related mortality (primary outcome), overall neonatal mortality and
      morbidity and health worker's performance on neonatal care (secondary outcomes).
      A process evaluation and a cost-effectiveness analysis will be performed to
      understand the functionality of the intervention and to further guide health
      system investments will also be performed. DISCUSSION: In contexts where
      resources are limited, there is a need to find scalable and sustainable
      implementation strategies for improved care delivery. The proposed study will add
      to the scarce evidence base on how to scale up interventions within existing
      health systems. If successful, the NePeriQIP model can provide a replicable
      solution in similar settings where support and investment from the health system
      is poor, and national governments have made a global pledge to reduce perinatal
      mortality. TRIAL REGISTRATION NUMBER: ISRCTN30829654.

PMID- 29071131
TI  - Understanding and defining sanitation insecurity: women's gendered experiences of
      urination, defecation and menstruation in rural Odisha, India.
AB  - BACKGROUND: Research suggests that the lived experience of inadequate sanitation
      may contribute to poor health outcomes above and beyond pathogen exposure,
      particularly among women. The goal of this research was to understand women's
      lived experiences of sanitation by documenting their urination-related,
      defecation-related and menstruation-related concerns, to use findings to develop
      a definition of sanitation insecurity among women in low-income settings and to
      develop a conceptual model to explain the factors that contribute to their
      experiences, including potential behavioural and health consequences. METHODS: We
      conducted 69 Free-List Interviews and eight focus group discussions in a rural
      population in Odisha, India to identify women's sanitation concerns and to build
      an understanding of sanitation insecurity. FINDINGS: We found that women at
      different life stages in rural Odisha, India have a multitude of unaddressed
      urination, defecation and menstruation concerns. Concerns fell into four domains:
      the sociocultural context, the physical environment, the social environment and
      personal constraints. These varied by season, time of day, life stage and toilet
      ownership, and were linked with an array of adaptations (ie, suppression,
      withholding food and water) and consequences (ie, scolding, shame, fear). Our
      derived definition and conceptual model of sanitation insecurity reflect these
      four domains. DISCUSSION: To sincerely address women's sanitation needs, our
      findings indicate that more is needed than facilities that change the physical
      environment alone. Efforts to enable urinating, defecating and managing
      menstruation independently, comfortably, safely, hygienically, privately,
      healthily, with dignity and as needed require transformative approaches that also
      address the gendered, sociocultural and social environments that impact women
      despite facility access. This research lays the groundwork for future sanitation
      studies to validate or refine the proposed definition and to assess women's
      sanitation insecurity, even among those who have latrines, to determine what may
      be needed to improve women's sanitation circumstances.

PMID- 29071132
TI  - Do attributes of persons with chronic kidney disease differ in low-income and
      middle-income countries compared with high-income countries? Evidence from
      population-based data in six countries.
AB  - Kidney biopsies to elucidate the cause of chronic kidney disease (CKD) are
      performed in a minority of persons with CKD living in high-income countries,
      since associated conditions-that is, diabetes mellitus, vascular disease or
      obesity with pre-diabetes, prehypertension or dyslipidaemia-can inform management
      targeted at slowing CKD progression in a majority. However, attributes of CKD may
      differ substantially among persons living in low-income and middle-income
      countries (LMICs). We used data from population or community-based studies from
      five LMICs (China, urban India, Moldova, Nepal and Nigeria) to determine what
      proportion of persons with CKD living in diverse regions fit one of the three
      major clinical profiles, with data from the US National Health Nutrition and
      Examination Survey as reference. In the USA, urban India and Moldova, 79.0%
      83.9%; in China and Nepal, 62.4%-66.7% and in Nigeria, 51.6% persons with CKD fit
      one of three established risk profiles. Diabetes was most common in urban India
      and vascular disease in Moldova (50.7% and 33.2% of persons with CKD in urban
      India and Moldova, respectively). In Nigeria, 17.8% of persons with CKD without
      established risk factors had albuminuria >=300 mg/g, the highest proportion in
      any country. While the majority of persons with CKD in LMICs fit into one of
      three established risk profiles, the proportion of persons who have CKD without
      established risk factors is higher than in the USA. These findings can inform
      tailored CKD detection and management systems and highlight the importance of
      studying potential causes and outcomes of CKD without established risk factors in
      LMICs.

PMID- 29071133
TI  - Satellite SST-Based Coral Disease Outbreak Predictions for the Hawaiian
      Archipelago.
AB  - Predicting wildlife disease risk is essential for effective monitoring and
      management, especially for geographically expansive ecosystems such as coral
      reefs in the Hawaiian archipelago. Warming ocean temperature has increased coral
      disease outbreaks contributing to declines in coral cover worldwide. In this
      study we investigated seasonal effects of thermal stress on the prevalence of the
      three most widespread coral diseases in Hawai'i: Montipora white syndrome,
      Porites growth anomalies and Porites tissue loss syndrome. To predict outbreak
      likelihood we compared disease prevalence from surveys conducted between 2004 and
      2015 from 18 Hawaiian Islands and atolls with biotic (e.g., coral density) and
      abiotic (satellite-derived sea surface temperature metrics) variables using
      boosted regression trees. To date, the only coral disease forecast models
      available were developed for Acropora white syndrome on the Great Barrier Reef
      (GBR). Given the complexities of disease etiology, differences in host demography
      and environmental conditions across reef regions, it is important to refine and
      adapt such models for different diseases and geographic regions of interest.
      Similar to the Acropora white syndrome models, anomalously warm conditions were
      important for predicting Montipora white syndrome, possibly due to a relationship
      between thermal stress and a compromised host immune system. However, coral
      density and winter conditions were the most important predictors of all three
      coral diseases in this study, enabling development of a forecasting system that
      can predict regions of elevated disease risk up to six months before an expected
      outbreak. Our research indicates satellite-derived systems for forecasting
      disease outbreaks can be appropriately adapted from the GBR tools and applied for
      a variety of diseases in a new region. These models can be used to enhance
      management capacity to prepare for and respond to emerging coral diseases
      throughout Hawai'i and can be modified for other diseases and regions around the
      world.

PMID- 29071134
TI  - Solitaire Stent in the Treatment of Acute Ischemic Stroke with Large Cerebral
      Artery Occlusion.
AB  - OBJECTIVE: To investigate the effect of mechanical thrombectomy with solitaire
      stent in the treatment of acute ischemic stroke with large cerebral artery
      occlusion. METHODS: Fifteen acute ischemic stroke patients with a proximal
      intracranial occlusion in the anterior circulation were included within 6 hours
      after symptom onset (unknown time of onset allowed in wake upstroke). Patients
      with a large infarct core or poor collateral circulation on computed tomography
      (CT) and CT angiography were excluded. All patients were measured by the National
      Institutes of Health Stroke Scale (NIHSS) before and 24 hours after the
      procedure. The primary outcomes were reperfusion at 24 hours and a Thrombolysis
      in Cerebral Infarction (TICI) score of 2b or 3 indicates successful reperfusion.
      Secondary outcomes included the functional score on the Modified Rankin
      Scale(MRS) and NIHSS score at 90 days. Good Functional Outcome (GFO), is defined
      as mRS0-2 at 90 days. RESULTS: The preoperative TICI grading of these 15 patients
      were all level 0.14 patients were level 2b to level 3 after the thrombectomy, 1
      ipsilateral cervical carotid occlusion patient failed recanalization.14 patients
      with reperfusion at 24 hours showed good early neurologic improvement. The MRS
      score of all the 14 patients were<2 point at 90 days. There were no obvious
      adverse reactions and complications in these patients after mechanical
      thrombectomy. CONCLUSION: The application of mechanical thrombectomy with
      solitaire stent for the treatment of acute ischemic stroke with large cerebral
      artery occlusion is safe and time-efficient, which could improve the
      recanalization rate, decrease or even eliminate the application of thrombolytic
      drugs and reduce the rate of intracranial hemorrhage. Awake stroke patient can
      also benefit from thrombectomy.

PMID- 29071135
TI  - Grifolin Attenuates White Matter Lesion in Oxygen/Glucose Deprivation.
AB  - The present study evaluates the effect of grifolin (GFL) in oxygen/glucose
      deprivation (OGD) induced white matter lesion. Injury induced with OGD was found
      to be significant at the 9th h of OGD induction and the effect of GFL on the
      proliferation of oligodendrocyte precursor cells (OPCs) was assessed by CCK-8 and
      Hoechst 33258 assay at GFL 1, 5, 25, 50 and 100 MUm concentrations. Whereas
      immunocytochemistry was performed for the assessment of survival and apoptosis of
      OPCs, western blot assay and RT-PCR were performed after 8th day of OGD injury
      for the estimation of expressions of myelin basic protein (MBP) and inhibitor of
      DNA binding 2 (Id2) in OPCs respectively. Results of the study suggests that
      treatment with GFL significantly enhances the survival rate and decreases the
      apoptosis of OPCs in OGD induced injury model. Immunocytochemical staining of
      Oligodendrocyte transcription factor (Olig2) and Bromodeoxyuridine (Brdu) shows
      that GFL treatment improves the proliferation of OPCs than OGD group. Moreover
      data of western blot assay suggested that treatment with GFL significantly
      enhances the expressions of MBP and Olig2 than OGD. It was observed that
      expressions of Id2 decreases and Olig2 enhances in GFL treated group than OGD
      group. Data of our study concludes that GFL enhances the differentiation and
      proliferation of OPCs in OGD-induced injury by altering the expressions of Id2
      and Olig2.

PMID- 29071137
TI  - Effects of previous unsuccessful extracorporeal shockwave lithotripsy treatment
      on the performance and outcome of percutaneous nephrolithotomy.
AB  - OBJECTIVE: To evaluate the effects of previous unsuccessful extracorporeal
      shockwave lithotripsy (ESWL) treatment on the performance and outcome of
      percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: Of 1625 PCNL
      procedures performed in our clinic, 393 renal units with similar stone burden and
      number of accesses was included in the present study. We categorised the study
      patients into two groups according to whether they underwent ESWL within 1 year
      prior to PCNL or not. Accordingly, Group 1 comprised 143 (36.3%) ESWL-treated
      patients and Group 2 comprised 250 (63.7%) non-ESWL-treated patients. RESULTS:
      Residual stones were detected in 36 (25.1%) of the ESWL-treated patients (Group
      1) and in 60 (24%) of non-ESWL-treated patients (Group 2). There were no
      statistically significant differences between the groups for length of hospital
      stay (LOS), nephrostomy tube removal time, and the presence of residual stones.
      When we evaluated the groups for both the preoperative and postoperative
      haemoglobin (Hb) drop and blood transfusion rate, manifest Hb declines and more
      transfusions were required in the ESWL-treated patients (both P = 0.01).
      CONCLUSIONS: In our study, previous ESWL treatment had no influence on the PCNL
      stone-free rate, operation time, incidence of postoperative complications, and
      LOS, in patients with similar stone burdens. However, bleeding during PCNL was
      more prevalent in the ESWL-treated patients, so close attention should be paid to
      bleeding in patients who have been pretreated with ESWL.

PMID- 29071138
TI  - Photodynamic diagnosis in upper urinary tract urothelial carcinoma: A systematic
      review.
AB  - OBJECTIVE: To assess the diagnostic accuracy and safety of photodynamic diagnosis
      (PDD) in upper urinary tract urothelial carcinoma (UUTUC). MATERIALS AND METHODS:
      A systematic literature search was conducted. Included studies were assessed for
      the risks of bias and quality using appropriate tools. Dedicated data extraction
      forms were used. Diagnostic accuracy in terms of sensitivity and specificity were
      quoted whenever provided by individual studies. A combined toxicity profile of 5
      aminolevulinic acid (5ALA) was given after reviewing individual studies. RESULTS:
      In all, 17 studies were identified. After screening seven studies were included
      involving a total of 194 patients. None of the studies were randomised. All the
      available studies were of low-to-moderate quality. The largest available study,
      with 106 patients, reported a sensitivity of 95.8% and 53.5% for PDD and white
      light (WL) ureterorenoscopy (URS) respectively, with a statistically significant
      difference. The specificity was 96.6% for PDD and 95.2% for WL-URS with no
      statistical significance. PDD showed better ability in detecting carcinoma in
      situ and dysplasia. One study compared PDD to computed tomography urogram (CTU)
      and found PDD to have better sensitivity and statistically significantly better
      specificity. 5ALA-associated toxicity was minor in nature and hypotension was the
      most common adverse event. CONCLUSION: PDD in UUTUC appears to be more accurate
      than WL-URS and CTU, with no significant toxicity. Larger scale randomised trials
      are needed.

PMID- 29071139
TI  - Validation of the Arabic version of the Functional Assessment of Cancer Therapy
      Bladder questionnaire in Egyptian patients with bladder cancer.
AB  - OBJECTIVES: To validate the Arabic version of the Functional Assessment of Cancer
      Therapy-Bladder (FACT-Bl) questionnaire in Egyptian patients who underwent
      radical cystectomy (RC) and orthotopic neobladder (ONB) construction. PATIENTS
      SUBJECTS AND METHODS: The English version of the FACT-Bl was translated into the
      Arabic language using multi-step process by two urologist and two independent
      translators. The Arabic version was validated by inviting 90 patients who
      underwent RC and ONB and 72 normal individuals to complete the questionnaire. The
      reliability of the questionnaire was tested for internal consistency using the
      Cronbach's alpha test. Inter-domain association was tested by Spearman's
      correlation coefficient. The discrimination validity was measured by comparing
      the scores in RC patients and in normal individuals using the Mann-Whitney U-test
      and independent sample t-test. RESULTS: Internal consistency was high for all
      domains. There was high correlation between all domains. This high internal
      consistency and good correlation was maintained when assessment included patients
      with <7.5 and those with >=7.5 years follow-up. Discrimination validation was
      confirmed by the statistically significant lower scores of all domains in the
      studied patients in comparison to the controls. CONCLUSION: The Arabic version of
      the FACT-Bl is a reliable and validated instrument that can be used to evaluate
      health-related quality of life in patients after RC and ONB.

PMID- 29071136
TI  - Medical expulsive therapy for ureteric stones: Analysing the evidence from
      systematic reviews and meta-analysis of powered double-blinded randomised
      controlled trials.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis investigating the
      efficacy and safety of medical expulsive therapy (MET) in low risk of bias (RoB)
      randomised controlled trials (RCTs). METHODS: A Cochrane style systematic review
      was conducted on published literature from 1990 to 2016, to include low RoB and a
      power calculation. A pooled meta-analysis was conducted. RESULTS: The MET group
      included 1387 vs 1381 patients in the control group. The analysis reveals alpha
      blockers increased stone expulsion rates (78% vs 74%) (P < 0.001), whilst calcium
      channel blockers (CCBs) had no effect compared to controls (79% vs 75%) (P =
      0.38). In the subgroup analysis, alpha-blockers had a shorter time to stone
      expulsion vs the control group (P < 0.001). There were no significant differences
      in expulsion rates between the treatment groups and control group for stones <5
      mm in size (P = 0.48), proximal or mid-ureteric stones (P = 0.63 and P = 0.22,
      respectively). However, alpha-blockers increased stone expulsion in stones >5 mm
      (P = 0.02), as well as distal ureteric stones (P < 0.001). The alpha-blocker
      group developed more side-effects (6.6% of patients; P < 0.001). The numbers
      needed to treat for alpha-blockers was one in 14, for stones >5 mm one in eight,
      and for distal stones one in 10. CONCLUSION: The primary findings show a small
      overall benefit for alpha-blockers as MET for ureteric stones but no benefit with
      CCBs. alpha-blockers show a greater benefit for large (>5 mm) ureteric stones and
      those located in the distal ureter, but no benefit for smaller or more proximal
      stones. alpha-blockers are associated with a greater risk of side-effects
      compared to placebo or CCBs.

PMID- 29071141
TI  - Management of penile cancer in a Singapore tertiary hospital.
AB  - OBJECTIVES: To present our experience of managing penile squamous cell carcinoma
      (SCC) in a tertiary hospital in Singapore and to evaluate the prognostic value of
      the inflammatory markers neutrophil-lymphocyte ratio (NLR) and lymphocyte
      monocyte ratio (LMR). PATIENTS AND METHODS: We reviewed our prospectively
      maintained Institutional Review Board-approved urological cancer database to
      identify men treated for penile SCC at our centre between January 2007 and
      December 2015. For all the patients identified, we collected epidemiological and
      clinical data. RESULTS: In all, 39 patients were identified who were treated for
      penile SCC in our centre. The median [interquartile range (IQR)] follow-up was 34
      (16.5-66) months. Although very few (23%) of our patients with high-risk clinical
      node-negative underwent prophylactic inguinal lymph node dissection (ILND), they
      still had excellent 5-year recurrence-free survival (RFS; 90%) and cancer
      specific survival (CSS; 90%). At multivariate analysis, higher N stage was
      significantly associated with worse RFS and CSS. Patients with a high NLR (>=2.8)
      had significantly higher T-stage (P = 0.006) and worse CSS (P < 0.001) than those
      with a low NLR. Patients with a low LMR (<3.3) had significantly higher T-stage
      (P = 0.013) and worse RFS (P = 0.009) and CSS (P < 0.022) than those with a high
      LMR. CONCLUSIONS: Although very few of our patients with intermediate- and high
      risk clinical node-negative SCC underwent prophylactic ILND, they still had
      excellent 5-year RFS and CSS. However, survival was poor in patients with node
      positive disease. The pre-treatment NLR and LMR could serve as biomarkers to
      predict the prognosis of patients with penile cancer.

PMID- 29071140
TI  - A practical guide and decision-making protocol for the management of complex
      renal cystic masses.
AB  - OBJECTIVES: To analyse the management, pathology and outcomes of complex renal
      cystic masses (CRCM) and to develop a decision-making tool for daily clinical
      care using the Bosniak classification system for CRCM. PATIENTS AND METHODS: A
      comprehensive dataset of 185 patients with 188 CRCM and a minimum follow-up of 3
      years were analysed for management, pathology and outcomes. RESULTS: We analysed
      35 Bosniak II, 34 Bosniak IIF, 58 Bosniak III, and 61 Bosniak IV lesions. The
      overall incidence of renal cell carcinoma was 8.6%, 29.4%, 62.1%, and 78.7% for
      each category. Based on our surveillance strategy of Bosniak IIF masses, we
      recommend computed tomography (CT)/magnetic resonance imaging (MRI) every 2 years
      after the initial examination. We also recommend performing one MRI (as an
      adjunct to CT) during the early follow-up period (<4 years). The use of MRI
      correlation for differential diagnostic purposes has proven useful for marginal
      Bosniak II, IIF and III cases. CONCLUSIONS: From our data, we have created a
      decision-making protocol to guide urologists in planning a safe and effective
      diagnostic and treatment strategy for CRCM. The Bosniak classification is a
      useful tool for clinical decision-making. Uncertainties still remain for Bosniak
      IIF and III lesions. Our protocol shows that individualised decision-making is
      necessary in a significant proportion of CRCM.

PMID- 29071143
TI  - The prevalence of an excessive prepuce and the effects of distal circumcision on
      premature ejaculation.
AB  - OBJECTIVE: To investigate the prevalence of an excessive prepuce in patients with
      premature ejaculation (PE) and to evaluate the effectiveness of distal
      circumcision in reducing the penile hypersensitivity, which is thought to be a
      cause of PE. PATIENTS AND METHODS: Men were considered to have an excessive
      prepuce if the foreskin exceeded the external urethral meatus by >=1 cm in the
      flaccid state. The diagnosis of PE was based on the Premature Ejaculation
      Diagnostic Tool (PEDT) questionnaire score and on the intravaginal ejaculatory
      latency time (IELT). These features were evaluated at baseline and at 6 months
      after circumcision. RESULTS: Lifelong PE was diagnosed in 352 patients of whom
      208 (59.1%) had an excessive prepuce. We offered those with an excessive prepuce
      a circumcision, as a potential definitive treatment for their PE, and 27 (13%)
      men accepted. At 6 months after circumcision, there was an increase in the mean
      (SD) IELT from 40.4 (16.5) to 254 (66.8) s (P < 0.001) and the mean (SD) PEDT
      score decreased from 17 (2) to 6.6 (1.9) (P < 0.001). Overall, 26 of the 27 (96%)
      patients that had a circumcision reported an IELT increase. CONCLUSIONS: An
      excessive prepuce is very common in patients affected by PE. Although accepted by
      only 13% of our patients, distal circumcision was shown to be a very effective
      surgical treatment for definitive treatment of PE. We therefore recommend
      assessing patients complaining of lifelong PE for an excessive prepuce and if
      they have an excessive prepuce to suggest that they undergo distal circumcision.

PMID- 29071144
TI  - Does sacral pulsed electromagnetic field therapy have a better effect than
      transcutaneous electrical nerve stimulation in patients with neurogenic
      overactive bladder?
AB  - OBJECTIVE: To compare the effectiveness of pulsed electromagnetic field therapy
      (PEMFT) and transcutaneous electrical nerve stimulation (TENS) on neurogenic
      overactive bladder dysfunction (OAB) in patients with spinal cord injury (SCI).
      PATIENTS AND METHODS: In all, 80 patients [50 men and 30 women, with a mean (SD)
      age of 40.15 (8.76) years] with neurogenic OAB secondary to suprasacral SCI were
      included. They underwent urodynamic studies (UDS) before and after treatment.
      Patients were divided into two equal groups: Group A, comprised 40 patients who
      received 20 min of TENS (10 Hz with a 700 s generated pulse), three times per
      week for 20 sessions; Group B, comprised 40 patients who received PEMFT (15 Hz
      with 50% intensity output for 5 s/min for 20 min), three times per week for 20
      sessions. RESULTS: In Group B, there was a significant increase in the maximum
      cystometric capacity (P < 0.001), volume at first uninhibited detrusor
      contraction (P < 0.002), and maximum urinary flow rate (P < 0.02). CONCLUSION:
      The UDS showed that the effects of PEMFT in patients with neurogenic OAB
      secondary to suprasacral SCI was better than TENS for inducing an inhibitory
      effect on neurogenic detrusor overactivity.

PMID- 29071142
TI  - The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on
      the outcome of varicocelectomy in infertile patients: A prospective controlled
      study.
AB  - OBJECTIVES: To study the relationship between sperm DNA fragmentation (SDF) and
      reactive oxygen species (ROS) levels in infertile patients with varicocele, and
      to examine the beneficial effect of varicocelectomy and elucidate predictors of
      improvement after repair. PATIENTS SUBJECTS AND METHODS: We prospectively studied
      60 patients with varicocele and abnormal semen variables who attended the
      outpatient clinic complaining of infertility for >=12 months. In all, 25 patients
      (41.7%) had bilateral varicoceles and 35 (58.3%) had left varicoceles. The DNA
      fragmentation index (DFI%, percentage of sperm with denatured nuclei), ROS and
      total non-enzymatic antioxidant capacity (TAC) were measured. Inguinal
      varicocelectomy was performed in all patients. At 3-6 months postoperatively, all
      measurements were repeated. A control group, comprised of 20 normozoospermic
      fertile men, was included. Regression analysis was used to examine predictors of
      improvement. RESULTS: The mean (SD) DFI% in the 60 infertile patients with
      varicocele was 29.9 (8.3) and 7.56 (2.84)% in the controls; ROS levels were 4.49
      (0.9) in patients and 2.62 (0.8) photons/min in controls; and the TAC was 0.97
      (0.4) in patients and 1.5 (0.5) mM in controls; with highly significant
      differences between the patients and controls. The DFI% showed a positive
      correlation with ROS levels, whilst the total motile sperm count (TMSC) had a
      significant negative correlation with DFI%, ROS levels and grade of varicocele,
      whilst there was significant positive correlation with TAC. The grade of
      varicocele and duration of infertility were related to the presence of higher
      levels of ROS and increased of DFI%. Postoperatively, improvement (measured as a
      >50% increase in TMSC) occurred in 40 of 55 (73%) patients available at follow
      up, with a significant reduction in the mean (SD) DFI% from 29.49 (8.58) to 18.78
      (7.23)%, ROS levels from 4.49 (0.88) to 3.27 (1.3) photons/min (both P < 0.001),
      and a significant increase in the mean (SD) TAC from 1.01 (0.44) to 2.05 (0.51)
      mM (P < 0.001). Responders had a shorter infertility duration and lower
      preoperative DFI% and ROS levels. Regression analysis showed that DFI% is a
      predictor of improvement after varicocelectomy. CONCLUSION: SDF was shown to have
      a negative impact on improvement after varicocelectomy. Hence, DFI% could be
      recommended as a prognostic test in infertile patients with varicocele to help
      decision-making as regards the necessity and the anticipated outcome of
      varicocelectomy in patients with infertility.

PMID- 29071145
TI  - A novel algorithm for the non-invasive detection of bladder outlet obstruction in
      men with lower urinary tract symptoms.
AB  - OBJECTIVE: To determine the ability of bladder wall thickness (BWT) in
      combination with non-invasive variables to distinguish patients with bladder
      outlet obstruction (BOO). PATIENTS AND METHODS: Patients completed the
      International Prostate Symptom Score (IPSS) questionnaire and prostate size was
      measured by transrectal ultrasonography (US). Pressure-flow studies were
      performed to determine the urodynamic diagnosis. BWT was measured at 250-mL
      bladder filling using transabdominal US. Recursive partition analysis (RPA)
      recursively partitions data for relating independent variable(s) to a dependent
      variable creating a tree of partitions. It finds a set of cuts of the dependent
      variable(s) that best predict the independent variable, by searching all possible
      cuts until the desired fit is reached. RPA was used to test the ability of the
      combined data of BWT, maximum urinary flow rate (Qmax), post-void residual urine
      volume (PVR), IPSS, and prostate size to predict BOO. RESULTS: In all, 72
      patients were included in the final analysis. The median BWT, voided volumes,
      PVR, mean Qmax, and IPSS were significantly higher in patients who had an
      Abrams/Griffiths (A/G) number of >40 (55 patients) compared to those with an A/G
      number of <=40 (17 patients). RPA revealed that the combination of BWT and Qmax
      gave a correct classification in 61 of the 72 patients (85%), with 92%
      sensitivity and 65% specificity, 87% positive predictive value, and 76% negative
      predictive value (NPV) for BOO (area under the curve 0.85). The positive
      diagnostic likelihood ratio of this reclassification fit was 2.6. CONCLUSIONS: It
      was possible to combine BWT with Qmax to create a new algorithm that could be
      used as a screening tool for BOO in men with lower urinary tract symptoms.

PMID- 29071146
TI  - Posterior urethral valves: Impact of low birth weight and preterm delivery on the
      final renal outcome.
AB  - OBJECTIVE: To investigate the relationship between low birth weight (LBW; <2.5
      kg) and preterm delivery (<37 weeks gestational age) and final renal outcome in
      infants with posterior urethral valves (PUVs), emphasising the risk factors for
      the development of chronic kidney disease (CKD). PATIENTS AND METHODS: A
      retrospective review was performed for all infants with PUVs who were treated
      between 1990 and 2010. In all, 52 infants were identified to have LBW and/or
      delivered preterm (Group 1). Infants in Group 1 were compared with a matching
      group (Group 2) of 60 full-term normal birth weight (NBW) infants with PUVs
      managed during the same period. The outcome of both groups was analysed. RESULTS:
      During follow-up, CKD developed in 17 (32.5%) and 22 patients (36.5%) in Groups 1
      and 2, respectively (P = 0.812). Patients with LBW or delivered preterm had
      significantly higher incidence of oligohydramnios (P = 0.009), increased risk of
      vesicostomy (P < 0.001), longer hospital stay (P < 0.001), and higher incidence
      of vesico-ureteric reflux (VUR, P = 0.024). In the LBW patients, initial serum
      creatinine, nadir serum creatinine, oligohydramnios and Neonatal Intensive Care
      Unit (NICU) length of stay were significant predictors of final renal outcome (P
      < 0.001, P = 0.002, P = 0.004 and P = 0.012, respectively). CONCLUSION: In our
      cohort of LBW and preterm delivery infants with PUVs, outcomes were similar to
      those of NBW full-term infants with PUVs but with an increased risk of
      vesicostomy, longer hospital stay, and higher incidence of VUR. LBW was
      associated with oligohydramnios, longer NICU admission, high initial and nadir
      serum creatinine, which were associated with a poor prognosis.

PMID- 29071147
TI  - Simulators in the urological training armamentarium: A boon or a bane?
AB  - Simulation devices have grasped the attention of almost all industries worldwide
      and the medical field has not been exempt. With technological advancement, it
      becomes important to assess whether medical simulators are the way forward as an
      adjunct or as a replacement to traditional training approaches by assessing their
      safety, efficacy and cost-effectiveness, and whether they should be made
      mandatory in the curriculum of urology training. The present review aims to
      clarify some of these issues, as well as assess their role in urological training
      and present both the pros and cons of this simulation-based training.

PMID- 29071148
TI  - Minimally invasive basilic vein transposition in the arm or forearm for
      autogenous haemodialysis access: A less morbid alternative to the conventional
      technique.
AB  - OBJECTIVE: To devise a minimally invasive, less morbid yet effective alternative
      technique for basilic vein transposition (BVT) in the arm/forearm and to compare
      perioperative outcomes with the conventional technique. PATIENTS AND METHODS:
      Patients undergoing BVT in the last two years (June 2013 to June 2015) were
      included in the study and the results were analysed. All patients were
      preoperatively evaluated using colour Doppler ultrasonography performed by the
      operating surgeon himself. For minimally invasive BVT, two or three small 1-2 cm
      incisions were made to completely mobilise the basilic vein, transposed in an
      anterolateral arm/forearm tunnel, and then anastomosed to the brachial or radial
      artery in the forearm and arm, respectively. The incision in the conventional
      technique was along the full length of the basilic vein, with the rest of the
      procedure remaining the same. Complications, pain, analgesic use, maturation and
      primary patency rates were compared between the techniques. RESULTS: In all, 30
      patients underwent minimally invasive BVT and 34 patients underwent conventional
      BVT, with mean age of 52 and 55 years, respectively. The complications of wound
      haematoma (one vs four) and wound infection/dehiscence (two vs six) were less
      common in the minimally invasive BVT group compared to the conventional group.
      The analgesic requirement and visual analogue scale pain score was significantly
      less in the minimally invasive BVT group. All other variables assessed, such as
      maturation and primary patency rate at 1 year, were not significantly different
      between the groups. CONCLUSION: Minimally invasive dissection of the basilic vein
      for vascular access transposition is a safe, reliable procedure with patency and
      functional outcomes comparable with those of conventional BVT.

PMID- 29071149
TI  - Laparoscopic vs robotic nephroureterectomy: Is it time to re-establish the
      standard? Evidence from a systematic review.
AB  - OBJECTIVE: To conduct a systematic review of comparative studies of laparoscopic
      nephroureterectomy (LNU), the standard management for upper urothelial tumours,
      and robot-assisted NU (RANU) that has emerged as a viable alternative. METHODS:
      MEDLINE, EMBASE and the Cochrane Library were searched according to the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to
      identify all studies reporting on both LNU and RANU for upper urothelial tract
      tumours. RESULTS: In all, 1630 patients were included, of which 838 underwent LNU
      and 792 RANU. Three studies reported on mean operative time and found it to be
      less in LNU, with two reporting this to be significant (RANU 298 vs LNU 251 min,
      P = 0.03; 306 vs 234 min, respectively, P < 0.001). Both studies reporting on
      median node count found this to be higher in the robotic groups: RANU 5.5 vs LNU
      1.0 and RANU 21 vs LNU 11. Positive surgical margins (RANU 1.69% vs LNU 7.06%, P
      = 0.18), bladder recurrence (24.6% vs 36.89%, P = 0.09), and distant metastases
      (27.50% vs 17.50%, P = 0.29) were not significantly different between the two
      techniques. Disease-specific mortality did not differ between the two techniques
      (RANU 7.5% vs LNU 12.5%, P = 0.46), but postoperative mortality was reduced in
      RANU (0.14% vs 1.32%, P = 0.03). Overall complication rates were statistically
      lower in RANU, at 12.5% vs 18.8% (P < 0.001). CONCLUSIONS: This review suggests
      these techniques are equivalent in terms of perioperative and oncological
      performance. Furthermore, there may be a lower overall complication rate, as well
      as postoperative mortality in the robotic group. Further research in the form of
      a randomised controlled trial is warranted.

PMID- 29071150
TI  - Laparoendoscopic single-site surgery for the treatment of different urological
      pathologies: Defining the learning curve of an experienced laparoscopist.
AB  - OBJECTIVES: To define the learning curve of laparoendoscopic single-site surgery
      (LESS) of an experienced laparoscopist. PATIENTS AND METHODS: Patients who had
      LESS, since its implementation in December 2009 until December 2014, were
      retrospectively analysed. Procedures were divided into groups of 10 and scored
      according to the European Scoring System for Laparoscopic Operations in Urology.
      Different LESS indications were done by one experienced laparoscopist. Technical
      feasibility, surgical safety, outcome, as well as the number of patients required
      to achieve professional competence were assessed. RESULTS: In all, 179 patients
      were included, with mean (SD) age of 36.3 (17.5) years and 25.4% of the patients
      had had previous surgeries. Upper urinary tract procedures were done in 65.9% of
      patients and 54.7% of the procedures were extirpative. Both transperitoneal and
      retroperitoneal LESS were performed in 92.8% and 7.2% of the patients,
      respectively. The intraoperative and postoperative complication rates were 2.2%
      and 5.6% (Clavien-Dindo Grade II 3.9% and IIIa 1.7%), respectively. In all, 75%
      of intraoperative complications and all conversions were reported during the
      first 30 LESS procedures; despite the significantly higher difficulty score in
      the subsequent LESS procedures. One 5-mm extra port, conversion to conventional
      laparoscopy and open surgery was reported in 14%, 1.7%, and 1.1% of the cases,
      respectively. At mean (SD) follow-up of 39.7 (11.4) months, all the patients that
      underwent reconstructive LESS procedures but one were successful. CONCLUSION: In
      experienced hands, at least 30 LESS procedures are required to achieve
      professional competence. Although difficult, both conversion and complication
      rates of LESS are low in experienced hands.

PMID- 29071151
TI  - Silodosin in the treatment of distal ureteric stones in children: A prospective,
      randomised, placebo-controlled study.
AB  - OBJECTIVES: To evaluate the possible role of silodosin (a highly selective
      alpha1A-adrenoceptor antagonist) in facilitating the passage of distal ureteric
      stones (DUS) in children, as the role of alpha-blockers as medical expulsive
      therapy is well known in adults. PATIENTS AND METHODS: In all, 40 paediatric
      patients (27 boys and 13 girls) diagnosed with unilateral, single, radiopaque DUS
      of <10 mm were included in the study. Their mean (SD, range) age was 8.1 (2.7, 5
      17) years. The patients were randomly divided into two groups: Group A, received
      silodosin 4 mg as a single bedtime dose; and Group B, received placebo as a
      single bedtime dose. Ibuprofen was prescribed to both groups on-demand for pain
      episode relief. Patients were followed up biweekly for 4 weeks. The stone
      expulsion time and rate, pain episodes, analgesic use, and any adverse effects
      were recorded. RESULTS: The mean (SD) stone size in Group A was 6.6 (1.7) mm and
      in Group B was 6.7 (1.4) mm (P = 0.4). Two patients were lost to follow-up (one
      from each group), and one patient in Group A refused to complete the study. The
      stone-free rate at end of the 4-week treatment period was 88.8% in Group A vs
      73.6% in Group B (P = 0.4). The mean (SD) stone expulsion time was 7.0 (4.3) vs
      10.4 (4.7) days in groups A and B, respectively (P = 0.02). The mean (SD) number
      of pain episodes requiring ibuprofen was 2.3 (1.4) vs 4.7 (2.6) episodes in
      groups A and B, respectively (P < 0.001). Adverse effects (headache and
      dizziness) were recorded in three patients (16.7%) in Group A, which were mild
      and none of them discontinued treatment, whilst no adverse effects were recorded
      in Group B. CONCLUSIONS: The data in the present study show that silodosin can be
      safely used in the treatment of DUS in children for decreasing time to stone
      expulsion, pain episodes, and analgesic requirement.

PMID- 29071152
TI  - A novel percutaneous nephrolithotomy (PCNL) set: The 'Economical One-shot PCNL
      Set' (Ecoset).
AB  - OBJECTIVES: To suggest a novel disposable percutaneous nephrolithotomy (PCNL) set
      that we named the 'Economical One-shot PCNL Set' (Ecoset), which consists of a
      single 30-F dilator, 30-F sheath, and 8-F polyurethane dilator, as use of a 'one
      shot' dilatation technique during PCNL is becoming widespread. PATIENT AND
      METHODS: The medical records of 42 patients with kidney stones who had undergone
      'one-shot' PCNL from February 2014 to June 2016 were retrospectively reviewed and
      analysed. Demographic data, as well as the stone size, radiation exposure time,
      operation time, hospitalisation duration, rate of treatment success and
      complications, were recorded. RESULTS: The mean (SD, range) age of the patients
      was 44.43 (16.54, 11-72) years. The mean (SD) stone size was 35.12 (17.53) mm.
      The mean (SD) operation time was 54.58 (22.24) min. The mean (SD) fluoroscopic
      screening time was limited to 154.72 (117.48) s. Treatment success was achieved
      in 32 (76%) patients. The mean (SD) hospital stay was 3.09 (0.75) days. None of
      the patients had any major complications. Bleeding requiring blood transfusion
      was required in three patients. The cost of a disposable dilatation set for a
      single PCNL operation with a balloon set, a standard Amplatz set, or an Ecoset is
      ~$137, $120, or $27 (American dollars), respectively. CONCLUSIONS: The one-shot
      dilatation technique using the Ecoset for PCNL can be feasibly, safely, and
      effectively performed in almost every adult patient. The Amplatz dilator set and
      balloon dilator set have the disadvantage of relatively high cost, whereas the
      Ecoset is the cheapest 'disposable set' that can be used during PCNL surgery.

PMID- 29071153
TI  - Validity of a sponge trainer as a simple training model for percutaneous renal
      access.
AB  - OBJECTIVE: To evaluate the efficacy of our simply designed trainer for junior
      urologists to acquire the initial skills for percutaneous renal access (PRA).
      SUBJECTS AND METHODS: Three sponge sheets (60 * 50 * 10 cm) were arranged
      horizontally over each other. A rectangular groove was made in the middle sheet
      to accommodate an inflated balloon of a Foley catheter, radio-opaque metal balls,
      metal rings, or a plastic tube that were sequentially placed for the four
      training tasks. In each session, 18 trainees were asked to pass a
      fluoroscopically guided puncture needle from a surface point to the placed object
      in middle sheet. Clinical impact of training was evaluated by an experience
      survey on a 5-piont Likert scale (for model usefulness, tactile and fluoroscopic
      guidance feedback) and success rate in further mentored practice. RESULTS: There
      was a gradual increase in tasks' and sessions' scores over the training sessions.
      According to the experience survey after first clinical practice, the mean (SD)
      score for overall model usefulness by trainees was 3.8 (0.9) with high
      fluoroscopic guidance reality [3.6 (1.1)] but poor tactile realism [2.3 (0.9)].
      On mentored PRA, the success rate for trainees was 78.3%. CONCLUSION: Our early
      evaluation showed our novel, cost-effective and reproducible sponge trainer could
      be an effective training model for PRA with a beneficial impact on subsequent
      clinical practice.

PMID- 29071154
TI  - A naked-eye comparison of image quality between a portable versus a fixed camera
      system for digital flexible ureterorenoscopy - A single centre experience.
AB  - OBJECTIVE: To assess the image quality using the portable OTV-SI (Olympus,
      Southend, UK) light source system compared to a dedicated fixed standard stack
      system for flexible ureterorenoscopy (URS) as judged by the human eye. METHODS:
      We compared two differing flexible URS set-ups. The first was our normal
      completely digital fixed set-up, comprising a flexible ureteroscope and matching
      digital stack system (CLV-S40 PRO-6E, Olympus). The second set-up comprised the
      same digital ureteroscope but with a conventional non-digital stack system and
      the OTV-SI portable light source. Seven experienced urologists were asked to
      subjectively assess the quality of the video sequences with the naked eye. The
      image qualities assessed were as follows: colour, distortion, graininess, depth
      perception, contrast, and glare. Finally, they were asked to guess whether they
      were observing images from the normal fixed set-up or the portable set-up.
      Fisher's exact test was used to compare the two sets of nominal variables.
      RESULTS: There were no significant differences in the observation ratings between
      the fixed and portable systems, independent of observer or image settings. Also,
      the surgeons were not able to correctly guess which stack system had been used.
      CONCLUSION: For flexible URS imaging, the combination of a digital ureteroscope
      with a conventional non-digital stack system together with the OTV-SI portable
      light source was subjectively found not to be inferior to the completely digital
      fixed set-up. Thus, the cheaper and smaller portable system could be considered
      as an economical option without substantial loss of image quality, especially
      useful in developing countries.

PMID- 29071155
TI  - Risk factors and prognosis of intravesical recurrence after surgical management
      of upper tract urothelial carcinoma: A 30-year single centre experience.
AB  - OBJECTIVE: To review the incidence, predictors and prognosis of bladder cancer
      recurrence after management of upper tract urothelial carcinoma (UTUC). PATIENTS
      AND METHODS: We retrospectively reviewed patients who were surgically treated for
      UTUC from 1983 to 2013. The tumours were categorised according to the 1997 Tumour
      Node-Metastasis (TNM) staging and the three-tiered World Health Organization
      grading systems. The primary endpoint was the occurrence of any intravesical
      recurrence after treatment. We studied the possible risk factors that may
      contribute to development of intravesical recurrence, as well as the prognosis of
      the patients who had recurrence. RESULTS: In all, 297 patients were eligible for
      analysis. Recurrent bladder tumours occurred in 139 patients (46.8%). The mean
      (range) time to recurrence after surgery was 33 (6-300) months. Neither sex, past
      history of bladder tumours, concomitant bladder tumour, the side of the tumour,
      UTUC stage, grade, presence of carcinoma in situ or multicentricity at the time
      of diagnosis of UTUC, were significant predictors of intravesical tumour
      recurrence. Ureteric tumour was the only identified risk factor (P = 0.02). Post
      treatment bladder recurrence was a significant predictor of later urethral
      recurrence (P = 0.002). CONCLUSIONS: In our present series, bladder cancer
      recurrence of urothelial malignancy occurred in nearly half of the patients after
      surgical management of UTUC. Ureteric tumour was the only identifiable risk
      factor, thus patients with ureteric tumours may benefit from prophylactic
      intravesical chemoimmunotherapy. Bladder recurrence does not appear to affect the
      cancer-specific survival after surgical management of UTUC.

PMID- 29071156
TI  - Bipolar vs monopolar resection of bladder tumours of >3 cm in patients maintained
      on low-dose aspirin: A randomised clinical trial.
AB  - OBJECTIVE: To compare the safety and efficacy of bipolar vs monopolar
      transurethral resection of bladder tumour (TURBT) in patients maintained on low
      dose aspirin with tumours >3 cm. PATIENTS AND METHODS: A prospective randomised
      single-centre study was performed including 200 patients with bladder tumours of
      >3 cm, as measured by ultrasonography. All patients were using low-dose aspirin
      (81 mg/day), which was not stopped in the perioperative period. Patients were
      randomised into two groups: Group A, monopolar TURBT (M-TURBT); Group B, bipolar
      TURBT (B-TURBT). The primary endpoint of the study was the decrease in
      postoperative haemoglobin (Hb) concentration measured using an automated cell
      counter. The secondary endpoints of the study were intraoperative blood
      transfusion or the occurrence of urethral trauma during cystoscopy and the need
      for re-coagulation. RESULTS: The postoperative reduction in Hb concentration, was
      significantly lower in the B-TURBT group [mean (SD) 0.55 (0.26) g/dL] compared
      with the M-TURBT group [mean (SD) 1.24 (0.61) g/dL] (P < 0.001). There was also a
      significant difference (in favour of B-TURBT) between the groups in the mean
      postoperative reduction in haematocrit and the mean postoperative hospital stay.
      There was no significant difference between the groups for the occurrence of
      obturator jerk, bladder perforation, and the need for blood transfusion.
      CONCLUSION: B-TURBT in patients maintained on low-dose aspirin is better than M
      TURBT for minimising postoperative drop in Hb concentration.

PMID- 29071157
TI  - Looking beyond oral mucosa: Initial results of everted saphenous vein graft
      urethroplasty (eSVGU) in long anterior urethral strictures.
AB  - OBJECTIVE: To prospectively evaluate the feasibility and initial results of an
      everted saphenous vein graft (eSVG) as a dorsolateral onlay, in patients with
      long anterior urethral strictures and/or chronic tobacco users. PATIENTS AND
      METHODS: In all, 20 patients with long anterior urethral strictures (>7 cm)
      and/or chronic tobacco exposed oral mucosa were included in the study. The
      harvested SVG was hydro-distended, detubularised, and everted. Substitution
      urethroplasty using an eSVG was performed using a dorsolateral onlay technique.
      Symptoms were assessed using the International Prostate Symptom Score (IPSS) and
      uroflowmetry at 1, 3 and 6 months; and voiding and retrograde urethrograms, and
      urethroscopy were done at 3 months. Failure was defined as failure to void, need
      for interventions in form of direct-vision internal urethrotomy or
      endodilatation. RESULTS: Three patients were excluded because they underwent a
      staged urethroplasty. In all, 17 patients underwent eSVG substitution
      urethroplasty. The mean (SD, range) follow-up of our patients was 17.64 (5.23, 10
      26) months. The mean (SD, range) length of the strictured segment was 14 (2.5, 10
      18) cm and the length of the harvested SVG was 16.3 (2.7, 12-20) cm. The mean
      (SD) IPSS at 1, 3 and 6 months after catheter removal was 10 (2.8), 10 (3.4) and
      10 (1.4) and the quality-of-life score was 1.76 (0.5), 2.05 (1.0) and 2.05 (1.0),
      respectively. Postoperatively, endodilatation was required in two patients.
      Complete failure occurred in one patient. CONCLUSIONS: An eSVG, as a dorsolateral
      onlay graft, is a promising and prudent option for long anterior urethral
      strictures, especially in patients with poor oral hygiene and chronic tobacco
      use.

PMID- 29071158
TI  - Lingual mucosal graft two-stage Bracka technique for redo hypospadias repair.
AB  - OBJECTIVES: To report our initial experience in redo hypospadias repair with a
      lingual mucosal graft (LMG) using a two-stage Bracka technique. PATIENTS AND
      METHODS: This study was prospectively conducted and included 26 patients with
      hypospadias with failed previous repairs. All the patients had a LMG using a two
      stage Bracka technique. In the first stage, the harvested LMG, from the ventro
      lateral surface of the tongue, was implanted in a well-prepared vascularised bed
      in the ventral aspect of the penis. After 6 months, tubularisation of the well
      taken graft was completed. Tunica vaginalis or a dartos flap was used as second
      layer coverage of the neourethra. Success was defined as acceptable aesthetic and
      functional outcomes without any additional surgical interventions. RESULTS: The
      mean (SD) patient age was 5.15 (1.6) years. The mean (SD) LMG length was 3.82
      (0.9) cm and the width was 1.5 (0.5) cm. The mean (SD) number of previous repairs
      was 2.76 (1.1). The mean (SD) follow-up was 12 (2) months. Donor-site
      complications included: pain in all patients, with a pain score of >3 on the
      visual analogue pain scale (0-10) in 10 (38%); and speech problems in 19 (73%).
      First-stage complications were graft loss (n = 2) and contracture (n = 1). The
      second stage was completed in 23 patients resulting in the following significant
      complications: meatal stenosis plus fistula (n = 2), breakdown (n = 1).
      Successful hypospadias repair was achieved in 77% (20/26) of the patients.
      CONCLUSION: Lingual mucosa is a reliable and versatile graft material in the
      armamentarium of two-stage Bracka hypospadias repair with the merits of easy
      harvesting and minor donor-site complications.

PMID- 29071159
TI  - Mathieu technique with incision of the urethral plate versus standard tubularised
      incised-plate urethroplasty in primary repair of distal hypospadias: A
      prospective randomised study.
AB  - OBJECTIVE: To compare outcomes of the Mathieu incised-plate (Mathieu-IP)
      technique vs the standard tubularised incised-plate (TIP) technique for primary
      management of distal hypospadias. PATIENTS AND METHODS: Between April 2012 and
      August 2015, 66 patients (aged 15-60 months) with primary distal hypospadias were
      randomly allocated to two groups. Group 1 included 34 patients who underwent
      Mathieu-IP repair and Group 2 included 32 patients managed using the TIP
      technique for primary management of distal hypospadias. Postoperatively, all
      patients were examined weekly up to 1 month and then at 3 and 6 months.
      Perioperative data, complications and outcomes of both procedures were
      statistically analysed and compared. RESULTS: There were no statistically
      significant differences in patient demographics between the groups at baseline.
      There was no statistically significant difference in the mean (SD) operative time
      between Groups 1 and 2, at 95 (7.6) and 91.2 (8.1) min, respectively. There was
      no statistically significant difference in the shape of the urine stream at
      micturition or the neomeatus between the groups postoperatively. The rate of
      postoperative fistula was significantly higher in Group 2 (TIP) compared to Group
      1 (Mathieu-IP), at 18.7% vs 2.9% (P = 0.004). There was no postoperative meatal
      stenosis in Group 1, which did occur in five patients (15.6%) in Group 2 (P =
      0.002). CONCLUSION: The Mathieu-IP technique appeared to be better than the
      standard TIP technique with regard to postoperative fistula formation and meatal
      stenosis, and with acceptable cosmesis.

PMID- 29071160
TI  - Diagnosis and treatment of urethral prolapse in children: 16 years' experience
      with 89 Chinese girls.
AB  - OBJECTIVE: To review our experience and results in the diagnosis and treatment of
      urethral prolapse (UP) in Chinese girls. PATIENTS AND METHODS: We conducted a
      retrospective chart review of 89 consecutive girls (aged <16 years) with UP and
      without other complications, who received treatment for UP from January 1999 to
      January 2015 (a study period of 16 years) at the Children's Hospital of Chongqing
      Medical University, China. Data analysed included: age, symptoms, clinical
      findings, predisposing factors, management, and outcomes. RESULTS: The presenting
      symptoms in the 89 girls were: mass (54 girls), bleeding (34), and
      dysuria/straining at micturition (one). In all, 14 patients received conservative
      treatment as their symptoms were mild, and 75 were successfully treated by
      excision of the prolapsed urethral mucosa or ligation over a Foley catheter, as
      their symptoms were severe and recurred too frequently to be managed
      conservatively. The mean postoperative length of stay for ligation was 7.76 days
      and for excision was 4.57 days. Ligation over a Foley catheter had a longer
      hospital stay. CONCLUSIONS: UP is a rare condition occurring in prepubertal
      girls, evidenced by a urethral mass and bleeding. Increased physician awareness
      and early recognition of UP avoids unnecessary examinations and patient anxiety.

PMID- 29071162
TI  - Evaluation of the risk factors associated with the development of post
      transurethral resection of the prostate persistent bacteriuria.
AB  - OBJECTIVES: To determine the preoperative, intraoperative and postoperative risk
      factors that influence the development of persistent post-transurethral resection
      of the prostate (TURP) urinary tract infection (UTI) defined as pyuria and/or
      bacteriuria remaining for 3 weeks after surgery. PATIENTS AND METHODS: This is a
      prospective study including 100 patients scheduled for TURP. Urine analysis and
      culture was performed immediately after catheter removal, then at 1 and 3 weeks
      postoperatively, and the results were correlated to various preoperative,
      intraoperative and postoperative potential risk factors to detect any significant
      relation to persistent UTI. RESULTS: There was a statistically significant
      relationship between bacteriuria and the following risk factors: old age, past
      history of diabetes mellitus, large prostatic size, positive preoperative urine
      analysis and culture, preoperative catheter use, previous urological
      interventions, large size of sheath, long duration of operation, postoperative
      catheter events and postoperative manual wash. CONCLUSIONS: Many risk factors
      have been found to contribute to the development of post-TURP UTI and avoiding
      these factors can enhance recovery of patients undergoing TURP.

PMID- 29071161
TI  - Outcome analysis of transrectal ultrasonography guided aspiration versus
      transurethral resection of prostatic abscess: 10 years' experience from a
      tertiary care hospital.
AB  - OBJECTIVE: To compare the effectiveness and safety of two minimally invasive
      methods (transrectal aspiration vs transurethral resection (TUR)/deroofing) of
      treating prostatic abscess. PATIENTS AND METHODS: A retrospective study was
      conducted, from 2007 to 2016, of patients with prostatic abscesses not responding
      to antibiotics and/or with large (>2 cm) or multiple abscesses. Patients were
      divided into two groups depending on treatment received: Group A, transrectal
      aspiration; and Group B, TUR/deroofing of abscess. RESULTS: The most common
      clinical presentation was dysuria (81.8%), followed by urinary frequency (68.2%),
      and fever (36.4%). Acute urinary retention occurred in seven patients. The most
      common infective organism in both groups was Escherichia coli (43.9%). The mean
      (SD, range) prostate volume was 36 (6.4, 17-68) mL and 37 (7.3, 21-72) mL in
      Groups A and B, respectively. The mean (SD, range) volume of the abscess was
      51.24 (12.6, 21-215) mL and 48.34 (15.4, 15-240) mL in Groups A and B,
      respectively. Overall, 37 (84.1%) patients responded to treatment (68.4% in Group
      A and 96.0% in Group B, P < 0.23) after the first treatment session. Six patients
      in Group A and one patient in Group B had recurrence of abscess (P < 0.03). Of
      the six patients in Group A with recurrence, four patients had complete
      resolution after repeat aspiration (average 1-3 times). The mean (SD) follow-up
      duration was 17.25 (6.3) months. CONCLUSION: TUR of prostatic abscess is more
      effective (96%) than transrectal aspiration with a lesser hospital stay. However,
      transrectal aspiration was successful in 89% of cases, is less invasive and can
      be performed under local anaesthesia and or sedation.

PMID- 29071163
TI  - Resolution of Periodic Breathing in a Child with Idiopathic Pulmonary Arterial
      Hypertension.
AB  - Central sleep apnea (CSA) and periodic breathing are unusual findings described
      in pediatric patients with congestive heart failure. However, CSA has not been
      reported in children with pulmonary hypertension. We hereby report on a 10-year
      old girl with idiopathic pulmonary arterial hypertension who had frequent central
      events in a periodic breathing fashion seen in her polysomnography, which was
      normalized following medical treatment leading to improvement of the pulmonary
      pressures.

PMID- 29071165
TI  - Federated Tensor Factorization for Computational Phenotyping.
AB  - Tensor factorization models offer an effective approach to convert massive
      electronic health records into meaningful clinical concepts (phenotypes) for data
      analysis. These models need a large amount of diverse samples to avoid population
      bias. An open challenge is how to derive phenotypes jointly across multiple
      hospitals, in which direct patient-level data sharing is not possible (e.g., due
      to institutional policies). In this paper, we developed a novel solution to
      enable federated tensor factorization for computational phenotyping without
      sharing patient-level data. We developed secure data harmonization and federated
      computation procedures based on alternating direction method of multipliers
      (ADMM). Using this method, the multiple hospitals iteratively update tensors and
      transfer secure summarized information to a central server, and the server
      aggregates the information to generate phenotypes. We demonstrated with real
      medical datasets that our method resembles the centralized training model (based
      on combined datasets) in terms of accuracy and phenotypes discovery while
      respecting privacy.

PMID- 29071166
TI  - First record of the family Sphyrapodidae Gutu, 1980 (Crustacea: Peracarida:
      Apseudomorpha) with the description of a new species of Sphyrapus from the
      Colombian Caribbean.
AB  - A new sphyrapodid tanaidacean, Sphyrapus caribensis sp. nov. is described and a
      new record of Kudinopasternakia siegi is reported for the Colombian Caribbean
      based on samples collected during cruises in 2014-2015. The new species appears
      to be most closely related to the northeast Atlantic species, Sphyrapus
      malleolus. Sphyrapus caribensis can be distinguished from Sphyrapus malleolus by
      a combination of characters, including the maxillipedal basis without long distal
      seta, the number of setae on the distoventral margin of pereopods 1 and 2, and
      the number of plumose seta on the pleopod basis. A key for the separation of
      Sphyrapus species is presented.

PMID- 29071168
TI  - Bacterial community of a spider, Marpiss magister (Salticidae).
AB  - Arthropods are associated with various microorganisms which confer benefits to
      their hosts. Recently, research has been conducted on bacterial communities of
      insects to provide an insight into the potential interactions of the symbiotic
      bacteria and their hosts. Spiders are interesting to study as they are perceived
      to be natural enemies of pests. The effect of endosymbionts on spiders has been
      reported, but little is known about the overall bacterial communities present in
      spiders. Here, we report on the characterization of bacterial communities present
      in the whole body of the spider Marpiss magister using Illumina sequencing of 16S
      rRNA amplicons. Our study shows that the most abundant phyla of bacteria included
      Proteobacteria, Tenericutes, Bacteroidetes and Actinobacteria. At the genus
      level, the most abundant genera included Rickettsia, Wolbachia, Spiroplasma, and
      Cardinium. Besides these dominant endosymbionts, our study also showed the
      existence of bacteria in the genera Arthrobacter, Novosphingobium, Acinetobacter,
      Pseudomonas, Aquabacterium and Sphingomonas at an abundance ranging from 0.65 to
      0.84%, and the existence of bacterial in genera Lactobacillus, Sphingobium,
      Methylobacterium, Bradyrhizobium, Propionibacterium, Brevundimonas,
      Achromobacter, Microbacterium, Corynebacterium, and Flavobacterium at a slightly
      lower abundance ranging from 0.1 to 0.5%. Therefore, our finding indicates that
      endosymbionts are not the only microbiota present in the spider M. magister, and
      other bacterial taxa also exist in its bacterial community.

PMID- 29071167
TI  - 16S rDNA analysis of the effect of fecal microbiota transplantation on pulmonary
      and intestinal flora.
AB  - This study aims to explore the effect of FMT on regulations of dysbacteriosis of
      pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A
      total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups:
      normal control group (K), model control group (MX), and fecal microbiota
      transplantation group (FMT); each group contained nine rats. The OTU values of
      the pulmonary and intestinal flora of the MX group decreased significantly
      compared with the normal control group. After FMT, the OTU value of pulmonary
      flora increased, while the value of OTU in intestinal flora declined. At the
      phylum level, FMT down-regulated Proteobacteria, Firmicutes, and Bacteroidetes in
      the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas,
      Sphingobium, Lactobacillus, Rhizobium, and Acinetobacter, thus maintaining the
      balance of the pulmonary flora. Moreover, FMT could change the structure and
      diversity of the pulmonary and intestinal flora by positively regulating the
      pulmonary flora and negatively regulating intestinal flora. This study may
      provide a scientific basis for FMT treatment of respiratory diseases.

PMID- 29071169
TI  - Draft genome sequence of a thermostable, alkaliphilic alpha-amylase and protease
      producing Bacillus amyloliquefaciens strain KCP2.
AB  - Bacillus amyloliquefaciens strain KCP2 was isolated from municipal food waste
      samples collected in Vallabh Vidyanagar, Gujarat, India. Strain KCP2 is
      noteworthy due to its ability to produce a thermostable, alkaliphilic alpha
      amylase and a protease. These enzymes have importance in several industrial
      processes including bread making, brewing, starch processing, pharmacy, and
      textile industries. Whole genome sequencing of strain KCP2 showed that the
      estimated genome size was 3.9 Mb, the G + C content was 46%, and it coded for
      4113 genes.

PMID- 29071170
TI  - Comparative assessment of four RNA extraction methods and modification to obtain
      high-quality RNA from Parthenium hysterophorus leaf.
AB  - Isolation of high-quality RNA from weed plants such as Parthenium hysterophorus
      is a difficult task due to the hindrance caused by numerous secondary
      metabolites. Such metabolites not only affect the quality and yield of RNA, but
      also limit the quality of downstream applications. Therefore, the present study
      was undertaken to design a protocol for yielding RNA with better quality and
      quantity from P. hysterophorus leaf which could be suitable for functional
      genomics. To achieve the objective, four different important RNA extraction
      protocols, viz. acid guanidinium thiocyanate-phenol-chloroform, phenol-LiCl
      precipitation, TRIzol(r), and PVP-ethanol were tested. The PVP-ethanol method
      proved to be best among the tested protocols. This method was further modified
      for obtaining improved quality and yield of RNA. The modified method successfully
      enhanced the yield of RNA from 280 to 334 ug g-1 fresh weight. The absorbance
      ratio (A260/A280) was in the purity range of 1.9 that indicated the good quality
      of RNA. To prove the feasibility of the extracted RNA in PCR-based cDNA
      synthesis, actin transcripts were targeted and successfully amplified using
      suitable primers. The improved protocol thus not only improved the yield and
      quality of RNA, but also gave better results in reverse transcriptase PCR.

PMID- 29071171
TI  - Role of calcium-depositing bacteria Agrobacterium tumefaciens and its influence
      on corrosion of different engineering metals used in cooling water system.
AB  - The present investigation deals with the role of calcium-depositing bacterial
      community on corrosion of various engineering metals, namely, brass alloy (BS),
      copper (Cu), stainless steel (SS) and mild steel (MS). Based on the corrosion
      behavior, Agrobacterium tumefaciens EN13, an aerobic bacterium is identified as
      calcium-depositing bacteria on engineering metals. The results of the study are
      supported with biochemical characterization, 16S rRNA gene sequencing, calcium
      quantification, weight loss, electrochemical (impedance and polarization) and
      surface analysis (XRD and FTIR) studies. The calcium quantification study showed
      carbonate precipitation in abiotic system/biotic system as 50 and 700 ppm,
      respectively. FTIR results too confirmed the accumulation of calcium deposits
      from the environment on the metal surface by EN13. Electrochemical studies too
      supported the corrosion mechanism by showing a significant increase in the charge
      transfer resistance (Rct) of abiotic system (44, 33.6, 45, 29.6 Omega cm2) than
      compared to biotic system (41, 10.1 29 and 25 Omega cm2). Hence, the outcome of
      the present study confirmed the enhanced bioaccumulation behavior of calcium by
      the strain, EN13.

PMID- 29071164
TI  - Biophysical Regulation of Cell Behavior-Cross Talk between Substrate Stiffness
      and Nanotopography.
AB  - The stiffness and nanotopographical characteristics of the extracellular matrix
      (ECM) influence numerous developmental, physiological, and pathological processes
      in vivo. These biophysical cues have therefore been applied to modulate almost
      all aspects of cell behavior, from cell adhesion and spreading to proliferation
      and differentiation. Delineation of the biophysical modulation of cell behavior
      is critical to the rational design of new biomaterials, implants, and medical
      devices. The effects of stiffness and topographical cues on cell behavior have
      previously been reviewed, respectively; however, the interwoven effects of
      stiffness and nanotopographical cues on cell behavior have not been well
      described, despite similarities in phenotypic manifestations. Herein, we first
      review the effects of substrate stiffness and nanotopography on cell behavior,
      and then focus on intracellular transmission of the biophysical signals from
      integrins to nucleus. Attempts are made to connect extracellular regulation of
      cell behavior with the biophysical cues. We then discuss the challenges in
      dissecting the biophysical regulation of cell behavior and in translating the
      mechanistic understanding of these cues to tissue engineering and regenerative
      medicine.

PMID- 29071173
TI  - Enhanced production of vanillin flavour metabolites by precursor feeding in cell
      suspension cultures of Decalepis hamiltonii Wight & Arn., in shake flask culture.
AB  - The flavour rich tuberous roots of Decalepis hamiltonii are known for its edible
      and medicinal use and have become endangered due to commercial over-exploitation.
      Besides 2-Hydroxy-4-methoxy benzaldehyde (2H4MB), other flavour metabolites in
      tuberous roots include vanillin, 4-Methoxy Cinnamic acid derivatives, aromatic
      alcohols etc. So far, there are no reports on the pathway of 2H4MB biosynthesis
      nor there is an organized work on biotransformation using normal and cell
      suspension cultures for obtaining these metabolites using precursors. The main
      aim of the study is to develop a method for enhanced production of flavour
      attributing metabolites through ferulic acid (FA) feeding to the D. hamiltonii
      callus culture medium. Biomass of D. hamiltonii cell suspension cultures was
      maximum (200.38 +/- 1.56 g/l) by 4th week. Maximum production of 2H4MB was
      recorded on 4th week (0.08 +/- 0.01 mg/100 g dry weight) as quantified by HPLC.
      Addition of 0.1-1.5 mM ferulic acid as precursor in the culture medium showed
      significant (p < 0.001) effect on suspension cultures biomass and respective
      phenylpropanoid metabolites content and 2H4MB accumulation. The maximum
      accumulation of vanillin, 2H4MB, vanillic acid, ferulic acid were of 0.1 +/- 0.02
      mg/100 g, 0.44 +/- 0.01 mg/100 g, 0.52 +/- 0.04 mg/100 g, 0.18 +/- 0.02 mg/100 g
      DW respectively in 4 weeks of cultured cells supplemented with 1 mM ferulic acid
      as a precursor. The results indicate that, substantial increase in the levels of
      flavour metabolites in D. hamiltonii callus suspension culture was achieved. This
      would be having implications in biosynthesis of respective vanilla flavour
      attributing metabolites at very high levels for their large scale production.

PMID- 29071172
TI  - Biases during DNA extraction affect bacterial and archaeal community profile of
      anaerobic digestion samples.
AB  - The anaerobic digestion (AD) of organic waste for biogas production has received
      much attention in recent years due to the increasing need for renewable energy
      and environmentally friendly waste management systems. Identification of the
      microbial community involved in AD aids in better understanding and optimising of
      the process. The choice of DNA extraction method is an integral step in any
      molecular biodiversity study. In the present study, potential biases introduced
      by DNA extraction methods were examined by comparing quality, quantity and
      representability of DNA extracted from AD samples using various extraction
      methods. In spite of the non-kit based method (cetyltrimethylammonium bromide)
      yielding the largest quantity of DNA (approximately 44 ug DNA per gram dry
      weight), the extracted DNA contained PCR inhibitors. Furthermore, the quantity of
      extracted DNA was not proportional to species diversity. Diversity, determined
      using denaturing gradient gel electrophoresis (DGGE), was strongly linked to the
      type of extraction method used. The spin-column filter-based kit that
      incorporated mechanical and chemical lysis (Macherey-Nagel kit) gave the best
      results in terms of bacterial and archaeal diversity (Shannon-Wiener indices:
      average 2.5 and 2.6, respectively). Furthermore, this kit was the most effective
      at lysing hard-to-lyse bacterial and archaeal cells. The choice of DNA extraction
      method significantly influences the reliability and comparability of results
      obtained during AD microbial ecology investigations. Moreover, the careful
      selection of the DNA extraction method is of particular importance when analysing
      AD samples since these samples are rich in PCR inhibitors and hard-to-lyse cells
      such as archaea and gram-positive bacteria.

PMID- 29071174
TI  - Optimized extraction process and identification of antibacterial substances from
      Rhubarb against aquatic pathogenic Vibrio harveyi.
AB  - Response surface optimization was applied for the extraction of antibacterial
      substances from Rhubarb (ASR) against aquatic pathogenic Vibrio harveyi. Based on
      the experimental results of single factors, the optimal extraction conditions
      were determined by Box-Behnken design combined with response surface methodology
      with conditions: 100% ethanol as extraction solvent, liquid/material ratio of 29
      mL/g and extraction temperature at 88  degrees C for 148 min. The factual value
      of inhibition zones can reach 21.31 +/- 0.95 mm and is not different from the
      predicted value (21.74 mm), which showed that the response surface methodology
      applied to the extraction optimization of antibacterial substances from Rhubarb
      against V. harveyi is feasible. Moreover, the yield of ASR was 30.29 +/- 2.27%.
      Five compounds, namely, aloe-emodin, rhein, emodin, chrysophanol and physcion,
      were identified in ASR by comparing the HPLC chromatogram of the reference
      mixtures and the sample. Contents of the five compounds were 0.68 +/- 0.02, 0.24
      +/- 0.05, 0.78 +/- 0.07, 6.68 +/- 0.97 and 0.58 +/- 0.15%, respectively. The
      minimal inhibitory concentration (MIC) values of ASR, aloe-emodin, rhein, emodin,
      chrysophanol and physcion were 0.625, 0.125, 0.015, > 1, > 1, and > 1 mg/mL,
      respectively, which indicated that aloe-emodin and rhein are the main
      antibacterial compounds of Rhubarb.

PMID- 29071175
TI  - Phytochemical profile, aldose reductase inhibitory, and antioxidant activities of
      Indian traditional medicinal Coccinia grandis (L.) fruit extract.
AB  - Coccinia grandis (L.) fruits (CGFs) are commonly used for culinary purposes and
      has several therapeutic applications in the Southeast Asia. The aim of this work
      was to evaluate phytochemical profile, aldose reductase inhibitory (ARI), and
      antioxidant activities of CGF extract. The CGFs were extracted with different
      solvents including petroleum ether, dichloromethane, acetone, methanol, and
      water. The highest yield of total extractable compounds (34.82%) and phenolic
      content (11.7 +/- 0.43 mg of GAE/g dried extract) was found in methanol extract,
      whereas water extract showed the maximum content of total flavonoids (82.8 +/-
      7.8 mg QE/g dried extract). Gas chromatography-mass spectroscopy (GC-MS) analysis
      of methanol and water extract revealed the presence of flavonoids, phenolic
      compounds, alkaloids, and glycosides in the CGFs. Results of the in vitro ARI
      activity against partially purified bovine lens aldose reductase showed that
      methanol extract of CGFs exhibited 96.6% ARI activity at IC50 value 6.12 ug/mL
      followed by water extract 89.1% with the IC50 value 6.50 ug/mL. In addition,
      methanol and water extracts of CGF showed strong antioxidant activities including
      ABTS*+ scavenging, DPPH* scavenging, and hydroxyl radical scavenging. Our results
      suggest that high percentage of both flavonoids and phenolic contents in the CGFs
      are correlated with the ARI and antioxidant activities. The fruits of C. grandis
      are thus potential bifunctional agents with ARI and antioxidant activities that
      can be used for the prevention and management of DM and associated diseases.

PMID- 29071176
TI  - Overexpression of herbaceous peony miR156e-3p improves anthocyanin accumulation
      in transgenic Arabidopsis thaliana lateral branches.
AB  - microRNAs (miRNAs) play critical regulatory roles in plant growth and
      development. In the present study, the function of herbaceous peony (Paeonia
      lactiflora Pall.) miR156e-3p in the regulation of color formation has been
      investigated. Firstly, P. lactiflora miR156e-3p precursor sequence (pre-miR156e
      3p) was isolated. Subsequently, the overexpression vector of pre-miR156e-3p was
      constructed and transformed into Arabidopsis thaliana. Moreover, the medium
      screening, GUS staining, polymerase chain reaction (PCR) of the GUS region and
      real-time quantitative PCR (qRT-PCR) of miR156e-3p all confirmed that the purpose
      gene had been successfully transferred into Arabidopsis plants and expressed,
      which resulted in apparent purple lateral branches. And this change in color was
      caused by the improved anthocyanin accumulation. In addition, expression analysis
      had shown that the level of miR156e-3p transcript was increased, while
      transcription level of target gene squamosa promoter binding protein-like gene
      (SPL1), encoding SPL transcription factor that negatively regulated anthocyanin
      accumulation, was repressed in miR156e-3p-overexpressing transgenic plants, and
      its downstream gene dihydroflavonol 4-reductase gene (DFR) that was directly
      involved in anthocyanin biosynthesis was strongly expressed, which resulted in
      anthocyanin accumulation of Arabidopsis lateral branches. These findings would
      improve the understanding of miRNAs regulation of color formation in P.
      lactiflora.

PMID- 29071177
TI  - Effects of Cd-based Quantum Dot Exposure on the Reproduction and Offspring of
      Kunming Mice over Multiple Generations.
AB  - The potential health risks associated with heavy-metal containing quantum dots
      (QDs) are a major concern accompanying their increased application in both
      research and industry. In this contribution, we investigate the effects of QDs on
      reproductive outcomes in Kunming mice across three generations. Rather than being
      exposed to QDs during pregnancy, mice were intravenously injected with
      phospholipid micelle encapsulated CdSe/CdS/ZnS QDs at a dosage of 0.81 mg Cd/kg
      two weeks before mating. Four treatment groups were studied: non-injected
      control, female injected, male injected and both parents injected with QDs.
      Although QDs accumulated in the major organs of treated mice, we did not detect
      any pregnancy complications or adverse effects. No significant difference in
      pregnancy outcomes could be identified between the QD treated groups and the
      control group. More importantly, through behavior monitoring, blood tests and
      histological evaluations, two generations of the offspring were observed to be in
      normal and healthy condition. Our results show that QD exposure with a short
      buffering period before conception does not cause obvious pregnancy complications
      or significant toxicity effects in treated mice or their offspring. This
      indicates that a short buffering period after QD exposure may reduce potential
      risk of QDs to reproductive health.

PMID- 29071180
TI  - A Vascular Permeability Assay Using an In Vitro Human Microvessel Model Mimicking
      the Inflammatory Condition.
AB  - The vascular barrier is an important function of the endothelium and its
      dysfunction is involved in several diseases. The barrier function of the
      endothelial cell monolayer is governed by cell-cell, cell-extracellular matrix
      (cell-ECM) contacts, and inflammatory factors such as thrombin, histamine or
      vascular endothelial growth factor. Several in vivo and in vitro assays that
      measure the vascular permeability induced by these factors have been developed.
      However, they suffer limitations such as being challenging for assessing details
      of biological processes at a cellular level or lacking the architecture of a
      vessel, that raise the need for new methods. In vitro 3D model-based assays have
      thus been developed but assays for investigating compounds that protects the
      barrier function are lacking. Here we describe the development of an in vitro
      three-dimensional (3D) vascular endothelium model in which we can manipulate the
      endothelial barrier function and permeability to molecules, which have a
      molecular weight similar to human serum albumin, allowing to assess the
      protective effect of compounds. A microvessel was prepared by culturing human
      umbilical vein endothelial cells (HUVECs) within a collagen gel on a
      polydimethylsiloxane (PDMS) chip. Using fluorescein isothiocyanate (FITC)
      conjugated dextran (70 kDa, FITC-dextran) and confocal fluorescence microscopy,
      we showed that the microvessel presented an effective barrier function. We were
      then able to induce the loss of this barrier function by treatment with the
      inflammatory factor thrombin. The loss of barrier function was quantified by the
      extravasation of FITC-dextran into collagen matrix. Furthermore, we were able to
      analyze the protective effect on the endothelial barrier function of the cyclic
      adenosine monophosphate (cAMP) analog, 8-pCPT-2'-O-Me-cAMP (also called 007). In
      an attempt to understand the effects of thrombin and 007 in our model, we
      analyzed the adherens junctions and cytoskeleton through immunostaining of the
      vascular endothelial cadherin and actin, respectively. Our assay method could be
      used to screen for compounds modulating the barrier function of endothelial
      cells, as well as investigating mechanistic aspects of barrier dysfunction.

PMID- 29071182
TI  - Engineering Quantum Dots with Different Emission Wavelengths and Specific
      Fluorescence Lifetimes for Spectrally and Temporally Multiplexed Imaging of
      Cells.
AB  - In this work, a proof-of-concept study was performed to examine the potential of
      spectrally and temporally multiplexed imaging of cells by using quantum dots
      (QDs). The CdSe and ZAIS QDs with different emission wavelengths and well
      separated fluorescence lifetimes were prepared to provide 2-dimensional
      information. After incubation with cells, the same type of QDs with different
      emission wavelengths were distinguishable in spectral imaging while different
      types of QDs with similar emission wavelengths but well-separated fluorescence
      lifetimes were resolvable in fluorescence lifetime imaging. For cells co-stained
      with dye and different types of QDs, the fluorescence lifetime imaging microscopy
      (FLIM) images showed spatially separated patterns that can be split into channel
      images by using the software-based time gates. Overall, the results demonstrate
      the feasibility of combining the 2-dimensional encoded QDs for spectrally and
      temporally multiplexed imaging. This method can be extended to other QDs and
      organic dyes to maximize the number of measurable species in multiplexed imaging
      and sensing applications.

PMID- 29071179
TI  - Novel Hyaluronic Acid Conjugates for Dual Nuclear Imaging and Therapy in CD44
      Expressing Tumors in Mice In Vivo.
AB  - Hyaluronic acid, a natural CD44 receptor ligand, has attracted attention in the
      past years as a macromolecular delivery of anticancer agents to cancer. At the
      same time, the clinical applications of Gemcitabine (Gem) have been hindered by
      its short biological half-life, high dose and development of drug resistance.
      This work reports the synthesis of a hyaluronic acid (HA) conjugate for nuclear
      imaging, and in vivo Gem delivery to CD44-expressing solid tumors in mice. HA was
      individually conjugated, via amide coupling, to Gem (HA-Gem), 4'
      (aminomethyl)fluorescein hydrochloride (HA-4'-AMF) or tris(hydroxypyridinone)
      amine (HA-THP) for cancer therapy, in vitro tracking or single photon emission
      computed tomography/computed tomography (SPECT/CT) imaging, respectively. Gem
      conjugation to HA was directly confirmed by nuclear magnetic resonance (1H NMR),
      gel permeation chromatography (GPC) and UV-visible spectrometry, or indirectly by
      a nucleoside transporter inhibition study. Gem conjugation to HA improved its
      plasma stability, reduced blood hemolysis and resulted in delayed cytotoxicity in
      vitro. Uptake inhibition studies in colon CT26 and pancreatic PANC-1 cells, by
      flow cytometry, revealed that uptake of fluorescent HA conjugate is CD44 receptor
      and macropinocytosis-dependent. Gamma scintigraphy and SPECT/CT imaging confirmed
      the relatively prolonged blood circulation profile and uptake in CT26 (1.5 %
      ID/gm) and PANC-1 (1 % ID/gm) subcutaneous tumors at 24 h after intravenous
      injection in mice. Four injections of HA-Gem at ~15 mg/kg, over a 28-day period,
      resulted in significant delay in CT26 tumor growth and prolonged mice survival
      compared to the free drug. This study reports for the first time dual nuclear
      imaging and drug delivery (Gem) of HA conjugates to solid tumors in mice. The
      conjugates show great potential in targeting, imaging and killing of CD44-over
      expressing cells in vivo. This work is likely to open new avenues for the
      application of HA-based macromolecules in the field of image-guided delivery in
      oncology.

PMID- 29071181
TI  - Heparin-Regulated Prodrug-Type Macromolecular Theranostic Systems for Cancer
      Therapy.
AB  - Heparin is a kind of naturally occurring polymer with excellent biocompatibility
      and solubility. It is characterized by dense of negative charge, higher than any
      endogenous components. Heparin can bind with various cationic peptides and
      proteins, thereby providing a useful noncovalent linkage for building a drug
      delivery system. As a case in point, heparin/cell-penetrating peptides (CPP)
      interaction is strong, and remains stable in vivo. They can be used to modify
      different proteins, respectively, and subsequently, by simply mixing the modified
      proteins, a protein-protein conjugate can be form via the stable heparin/CPP
      linkage. This linkage could not be broken unless addition of protamine that bears
      higher cationic charge density than CPP, and CPP thus can be substituted and
      released. Of note, heparin is a potent antagonist of CPP, and their binding
      naturally inhibits CPP-mediated drug cell penetration. Based on this method, we
      developed a heparin-regulated macromolecular prodrug-type system, termed
      ATTEMPTS, for drug targeting delivery. In this review article, we mainly summary
      the application of ATTEMPTS in delivery of various macromolecular drugs for
      cancer therapy, and also introduce the heparin-regulated nanoprobes for tumor
      imaging.

PMID- 29071183
TI  - Satellite-like Gold Nanocomposites for Targeted Mass Spectrometry Imaging of
      Tumor Tissues.
AB  - We have developed a simple, rapid, high-throughput cancer diagnosis system using
      functional nanoparticles (NPs) consisting of poly(catechin) capped-gold NPs
      (Au@PC NPs) and smaller nucleolin-binding aptamer (AS1411) conjugated gold NPs
      (AS1411-Au NPs). The AS1411-Au NPs/Au@PC NP is used as a targeting agent in laser
      desorption/ionization mass spectrometry (LDI-MS)-based tumor tissue imaging. Self
      assembled core-shell Au@PC NPs are synthesized by a simple reaction of
      tetrachloroaurate(III) with catechin. Au@PC NPs with a well-defined and dense
      poly(catechin) shell (~40-60 nm) on the surface of each Au core (~60-80 nm) are
      obtained through careful control of the ratio of catechin to gold ions, as well
      as the pH of the reaction solution. Furthermore, we have shown that AS1411
      conjugated Au NPs (13-nm) self-assembled on Au@PC NP can from a satellite-like
      gold nanocomposite. The high density of AS1411-Au NPs on the surface of Au@PC NP
      enhances multivalent binding with nucleolin molecules on tumor cell membranes. We
      have employed LDI-MS to detect AS1411-Au NPs/Au@PC NPs labeled nucleolin
      overexpressing MCF-7 breast cancer cells through the monitoring of Au cluster
      ions ([Au n ]+; 1 <= n <= 3). The ultrahigh signal amplification from Au NPs
      through the formation of a huge number of [Au n ]+ ions results in a sensing
      platform with a limit of detection of 100 MCF-7 cells mL-1. Further, we have
      applied the satellite-like AS1411-Au NPs/Au@PC NP nanocomposite as a labeling
      agent for tumor tissue imaging by LDI-MS. Our nanocomposite-assisted LDI-MS
      imaging platform can be extended for simultaneous analysis of different tumor
      markers on cell membranes when using different ligand-modified metal
      nanoparticles.

PMID- 29071178
TI  - Targeted Nanomaterials for Phototherapy.
AB  - Phototherapies involve the irradiation of target tissues with light. To further
      enhance selectivity and potency, numerous molecularly targeted photosensitizers
      and photoactive nanoparticles have been developed. Active targeting typically
      involves harnessing the affinity between a ligand and a cell surface receptor for
      improved accumulation in the targeted tissue. Targeting ligands including
      peptides, proteins, aptamers and small molecules have been explored for
      phototherapy. In this review, recent examples of targeted nanomaterials used in
      phototherapy are summarized.

PMID- 29071184
TI  - Nanoliposomes for Safe and Efficient Therapeutic mRNA Delivery: A Step Toward
      Nanotheranostics in Inflammatory and Cardiovascular Diseases as well as Cancer.
AB  - Rationale: Genetic therapy using modified mRNA for specific therapeutic protein
      expression for disease treatment and vaccination represents a new field of
      therapeutic and diagnostic medicine. Non-viral vectors transfection using
      biocompatible nanoliposomes enables safe and efficient delivery of therapeutic
      mRNA. Objective: Generation of non-toxic, cell-compatible cationic nanoliposomes
      as nanotheranostic agents to successfully deliver therapeutic mRNA. Methods and
      results: Cationic nanoliposomes (DC-Cholesterol/DOPE) were generated as
      transfection vehicles for either eGFP mRNA or the therapeutic anti-inflammatory,
      CD39 mRNA. We observed no toxicity using these nanoplexes and noted high cell
      viability after transfection. Nanoplexes for the transfection of eGFP mRNA showed
      an increase in fluorescence signals on microscopy as compared to the mRNA control
      after 24 hours in Chinese hamster ovary (CHO) cells (14.29 +/- 5.30 vs. 1.49 +/-
      0.54; mean +/- SD respectively; p<0.001) and flow cytometry (57.29 +/- 14.59 vs
      1.83 +/- 0.34; % mean +/- SD; p<0.001). Nanoplexes for the transfection of CD39
      mRNA showed increased CD39 expression in flow cytometry (45.64 +/- 15.3 vs. 3.94
      +/- 0.45; % mean +/- SD; p<0.001) as compared to the mRNA control after 24 hours
      using CHO cells. We also demonstrated efficient transfection across several cell
      lines (CHO, HEK293, and A549), as well as long-term protein expression (120 h and
      168 h) using these nanoplexes. Conclusions: We have developed and tested non
      toxic, safe, and efficient nanoliposome preparations for the delivery of
      therapeutic mRNA that hold promise for novel therapies in diseases such as
      inflammatory and cardiovascular diseases, as well as cancer. We have also
      demonstrated that this approach provides a reliable technology to deliver CD39
      mRNA as an anti-inflammatory therapeutic for future nanotheranostics approaches.

PMID- 29071186
TI  - Gold Nanorod-based Photo-PCR System for One-Step, Rapid Detection of Bacteria.
AB  - The polymerase chain reaction (PCR) has been an essential tool for diagnosis of
      infectious diseases, but conventional PCR still has some limitations with respect
      to applications to point-of-care (POC) diagnostic systems that require rapid
      detection and miniaturization. Here we report a light-based PCR method, termed as
      photo-PCR, which enables rapid detection of bacteria in a single step. In the
      photo-PCR system, poly(enthylene glycol)-modified gold nanorods (PEG-GNRs), used
      as a heat generator, are added into the PCR mixture, which is subsequently
      periodically irradiated with a 808-nm laser to create thermal cycling. Photo-PCR
      was able to significantly reduce overall thermal cycling time by integrating
      bacterial cell lysis and DNA amplification into a single step. Furthermore, when
      combined with KAPA2G fast polymerase and cooling system, the entire process of
      bacterial genomic DNA extraction and amplification was further shortened,
      highlighting the potential of photo-PCR for use in a portable, POC diagnostic
      system.

PMID- 29071185
TI  - Recent strategies to design vascular theranostic nanoparticles.
AB  - Vascular disease is a leading cause of death and disability worldwide. Current
      surgical intervention and treatment options for vascular diseases have exhibited
      limited long-term success, emphasizing the need to develop advanced treatment
      paradigms for early detection and more effective treatment of dysfunctional cells
      in a specific blood vessel lesion. Advances in targeted nanoparticles mediating
      cargo delivery enables more robust prevention, screening, diagnosis, and
      treatment of vascular disorders. In particular, nanotheranostics integrates
      diagnostic imaging and therapeutic function into a single agent, and is an
      emerging platform towards more effective and localized vascular treatment. This
      review article highlights recent advances and current challenges associated with
      the utilization of targeted nanoparticles for real-time diagnosis and treatment
      of vascular diseases. Given recent developments, nanotheranostics offers great
      potential to serve as an effective platform for targeted, localized, and
      personalized vascular treatment.

PMID- 29071188
TI  - Doxorubicin/Ce6-Loaded Nanoparticle Coated with Polymer via Singlet Oxygen
      Sensitive Linker for Photodynamically Assisted Chemotherapy.
AB  - It is widely known that the therapeutic effect of nanoparticle-based
      chemotherapeutics could be greatly enhanced by the introduction of the
      photodynamic effect. Herein we report a chlorin e6-incorporated mesoporous silica
      nanoparticles (MSNs) covered with a polyethylene glycol shell conjugated via a
      singlet oxygen-sensitive labile bis(alkylthio)alkene linker (CeAP-L-PEG). In this
      study, single irradiation with biocompatible red light induced both intracellular
      doxorubicin release and photochemical internalization, and consequently enhanced
      anti-cancer effect was observed in vitro and in vivo. This study suggests the
      potential of our precisely designed nanoparticle system for photodynamically
      assisted chemotherapy.

PMID- 29071187
TI  - Gadolinium and Platinum in Tandem: Real-time Multi-Modal Monitoring of Drug
      Delivery by MRI and Fluorescence Imaging.
AB  - A novel dual-imaging cisplatin-carrying molecular cargo capable of performing
      simultaneous optical and MR imaging is reported herein. This long-lasting MRI
      contrast agent (r1 relaxivity of 23.4 mM-1s-1 at 3T, 25 oC) is a photo-activated
      cisplatin prodrug (PtGdL) which enables real-time monitoring of anti-cancer
      efficacy. PtGdL is a model for monitoring the drug delivery and anti-cancer
      efficacy by MRI with a much longer retention time (24 hours) in several organs
      such as renal cortex and spleen than GdDOTA and its motif control GdL. Upon
      complete release of cisplatin, all PtGdL is converted to GdL enabling subsequent
      MRI analyses of therapy efficacy within its reasonably short clearance time of 4
      hours. There is also responsive fluorescence enhancement for monitoring by photon
      excitation.

PMID- 29071189
TI  - Black Phosphorus Nanosheets for Mild Hyperthermia-Enhanced Chemotherapy and Chemo
      Photothermal Combination Therapy.
AB  - Near-infrared (NIR) light triggered photothermally enhanced cellular
      internalization strategy shows great potential to improve antitumor effect to
      fight against cancer. In this work, a black phosphorus (BP) nanosheet-based
      nanomedicine, which is composed of BP nanosheet, human serum albumin (HSA) and
      paclitaxel (PTX), was developed for mild hyperthermia-enhanced intracellular drug
      delivery and chemo-photothermal combination therapy. BP nanosheet was
      successfully synthesized by a one-pot biomimetic synthesis method using HSA as
      exfoliating agent and capping agent. Meanwhile, PTX can be efficiently loaded by
      HSA via hydrophobic interactions. The PTX-loaded HSA functionalized BP (BP-HSA
      PTX) exhibits great photothermal performance, excellent
      biodegradability/biocompatibility, and effective drug loading. Upon NIR laser
      illumination, mild hyperthermia (~43  degrees C) or photothermal effect can be
      achieved to improve the intracellular drug delivery efficiency and antitumor
      effect of BP-HSA-PTX. Our results indicate that HSA-functionalized BP has great
      potential for the loading, delivery, cellular uptake enhancement of
      chemotherapeutics and chemo-photothermal combination antitumor effect.

PMID- 29071190
TI  - Accumulation of 111In-Labelled EGF-Au-PEG Nanoparticles in EGFR-Positive Tumours
      is Enhanced by Coadministration of Targeting Ligand.
AB  - The successful use of targeted radionuclide therapy in the treatment of solid
      tumours may be limited by radioresistance, which necessitates delivery of a high
      dose of radioactivity. Nanoparticle (NP)-based delivery systems possess a large
      surface area for attachment of radioisotopes and so offer a solution to this
      challenge. However, tumour uptake may be limited by rapid hepatic clearance of NP
      via the mononuclear phagocyte system. Liver uptake is further compounded when
      epidermal growth factor (EGF) is used as a targeting ligand, as EGF-tagged NP
      bind the EGF receptor (EGFR), which is expressed to a moderate extent by
      hepatocytes. This report describes an indium-111 (111In)-labelled PEGylated EGF
      tagged gold (Au) NP (111In-EGF-Au-PEG) and an effective strategy of
      coadministration of targeting ligand to address these issues. Direct attachment
      of EGF to the surface of Au NP did not compromise surface coating with long-chain
      PEG. In vitro experiments showed that 111In-EGF-Au-PEG targets EGFR-positive
      cancer cells (MDA-MB-468): >11% of radioactivity was internalised after
      incubation for 4 h. In in vivo studies accumulation of NP was observed in MDA-MB
      468 xenografts and tumour uptake was enhanced by the coadministration of 15 ug of
      the unlabelled targeting ligand, EGF, to block hepatic EGFR. Uptake was 3.9%
      versus 2.8% injected dose/g (%ID/g) of tumour tissue with and without unlabelled
      EGF, respectively. Coadministration of EGF reduced liver uptake by 25.95% to 7.56
      %ID/g. This suggests that the coadministration of unlabelled targeting ligand
      with radiolabelled PEGylated NP offers a promising strategy for targeting EGFR
      positive cancer and for minimising liver uptake.

PMID- 29071192
TI  - The biocompatibility studies of polymer dots on pregnant mice and fetuses.
AB  - Semiconducting polymer dots (Pdots) are small nanoparticles consisting primarily
      of fluorescent pi-conjugated polymers which show superior optical properties for
      biological imaging and biosensors. It is necessary to explore systematically the
      toxicity of Pdots on animals before extensive biomedical applications. The
      reproductive system is very sensitive to the external invasion and essential for
      species reproduction as well. In this work, we used the pregnant mice to
      investigate the reproductive toxicity of Pdots. The changes in body weight of
      each maternal mouse were recorded every two days. The main organs were collected
      and analyzed as soon as all the pregnant mice were sacrificed on the 15th
      embryonic day. Distributions of Pdots on maternal major organs and tissues were
      examined in frozen tissue sections. Hematoxylin and eosin (H&E) staining was
      performed to investigate the histopathological changes of maternal organs. The
      blood chemistry test was applied to study the effects of Pdots on organ
      functions. Female hormones were evaluated by immunoassays. The amniotic fluid was
      inspected for assessing their penetration ability of Pdots. Levels of placenta
      growth related factors were detected by RT-PCR to evaluate the function of
      placenta. These results showed that Pdots were mainly accumulated in liver and
      spleen, and no apparent impact was observed on maternal body weight and organs
      coefficients. Histopathological images also showed normal tissue morphology
      compared with the untreated group. The female hormones levels did not show
      significant difference among the three groups as well. Trace amount of Pdots
      could get into the amniotic fluid but did not change the placental functions and
      the early development of fetus. Our results demonstrated that Pdots have
      excellent biocompatibility and no reproductive toxicity under the dosages used in
      this work, which means that Pdots have great potential in preclinical
      applications in the future.

PMID- 29071191
TI  - Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune
      Potentiation.
AB  - Synthetic nanoparticles play an increasingly significant role in vaccine design
      and development as many nanoparticle vaccines show improved safety and efficacy
      over conventional formulations. These nanoformulations are structurally similar
      to viruses, which are nanoscale pathogenic organisms that have served as a key
      selective pressure driving the evolution of our immune system. As a result,
      mechanisms behind the benefits of nanoparticle vaccines can often find analogue
      to the interaction dynamics between the immune system and viruses. This review
      covers the advances in vaccine nanotechnology with a perspective on the
      advantages of virus mimicry towards immune potentiation. It provides an overview
      to the different types of nanomaterials utilized for nanoparticle vaccine
      development, including functionalization strategies that bestow nanoparticles
      with virus-like features. As understanding of human immunity and vaccine
      mechanisms continue to evolve, recognizing the fundamental semblance between
      synthetic nanoparticles and viruses may offer an explanation for the superiority
      of nanoparticle vaccines over conventional vaccines and may spur new design
      rationales for future vaccine research. These nanoformulations are poised to
      provide solutions towards pressing and emerging human diseases.

PMID- 29071195
TI  - Substitution of Percutaneous Ethanol Injection with a Low Molecular Weight
      Peptide Gel Mimicking Chemoembolization for Cancer Therapy.
AB  - In order to avoid the instability and quick separation between emulsifier and
      drug in the interventional chemoembolization, an injectable low molecular weight
      peptide gel (LMWG) was prepared to localize ethanol and chemotherapeutic for in
      situ synergistic therapy. The formation mechanism, rheological property and
      morphology of the LMWG were investigated by NMR, UV-vis, MS and SEM. The
      interaction between gelator and anticancer drug doxorubicin hydrochloride (DOX)
      was evaluated by fluorescence spectroscopy and its contribution on drug loading
      properties was demonstrated. The gel was non-toxic to both 3T3 fibroblasts and
      4T1 breast cancer cells. DOX as well as ethanol were encapsulated in the gel and
      injected in breast cancer bearing mice with low drug dose (2.5 mg/kg body
      weight). The LMWG surrounded tumors act as a depot for ethanol release and
      release DOX to induce the apoptosis of cancer cells. With the combination of
      percutaneous ethanol injection (PEI) and chemotherapy, the DOX loaded LMWG
      exhibited great significance in necrosis of tumor tissue and exciting tumor
      inhibition efficiency.

PMID- 29071196
TI  - TRAIL-functionalized gold nanoparticles selectively trigger apoptosis in
      polarized macrophages.
AB  - Tumor-associated macrophages (TAMs) have the same immunosuppressive effects as M2
      macrophages in tumor progression and are correlated with poor-patient prognosis
      and survival in non-small cell lung cancer (NSCLC). Therefore, TAMs are the
      potential targets for cancer therapy. Tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) is a member of tumor necrosis factor superfamily and
      selectively induces cancer cell apoptosis, but not in most normal cells.
      Nanoparticles coated with multiple ligands can act as multivalent ligands that
      may actively crosslink cell surface receptors to affect downstream signals. Here,
      we explored nanogolds coated with TRAIL protein (nanogold-TRAIL complexes) as a
      potential anti-M2 macrophage drug. The structure of nanogold-TRAIL complexes
      comprised nanogold (3, 13, or 30 nm) as the core to crosslink multiple TRAIL for
      exhibition of multivalent property. Nanogold-TRAIL complexes selectively
      increased the cytotoxicity of TRAIL (30-fold increase in IC50) via changing O
      glycosylation levels in M2-polarized macrophages. By testing the TRAIL complex
      efficacy on nanogold with different sizes and origins as well as on
      superparamagnetic iron oxide nanoparticles, we further demonstrated that the
      enhanced cytotoxicity by nanoparticles was dependent on size and surface
      properties of the nanoparticles. Meanwhile, the nanogold-TRAIL complexes remained
      nontoxic to M1 macrophages or normal cells. Nanogold-TRAIL complexes thus provide
      a novel and promising strategy for the improvement of TRAIL-based therapy.

PMID- 29071194
TI  - Prediction of Anti-cancer Nanotherapy Efficacy by Imaging.
AB  - Anticancer nanotherapeutics have shown mixed results in clinical trials, raising
      the questions of whether imaging should be used to i) identify patients with a
      higher likelihood of nanoparticle accumulation, ii) assess nanotherapeutic
      efficacy before traditional measures show response, and iii) guide adjuvant
      treatments to enhance therapeutic nanoparticle (TNP) delivery. Here we review the
      use of a clinically approved MRI nanoparticle (ferumoxytol, FMX) to predict TNP
      delivery and efficacy. It is becoming increasingly apparent that nanoparticles
      used for imaging, despite clearly distinct physicochemical properties, often co
      localize with TNP in tumors. This evidence offers the possibility of using FMX as
      a generic "companion diagnostic" nanoparticle for multiple TNP formulations, thus
      potentially allowing many of the complex regulatory and cost challenges of other
      approaches to be avoided.

PMID- 29071193
TI  - Recent Advances in Biosensor Development for Foodborne Virus Detection.
AB  - Outbreaks of foodborne diseases related to fresh produce have been increasing in
      North America and Europe. Viral foodborne pathogens are poorly understood,
      suffering from insufficient awareness and surveillance due to the limits on
      knowledge, availability, and costs of related technologies and devices. Current
      foodborne viruses are emphasized and newly emerging foodborne viruses are
      beginning to attract interest. To face current challenges regarding foodborne
      pathogens, a point-of-care (POC) concept has been introduced to food testing
      technology and device. POC device development involves technologies such as
      microfluidics, nanomaterials, biosensors and other advanced techniques. These
      advanced technologies, together with the challenges in developing foodborne virus
      detection assays and devices, are described and analysed in this critical review.
      Advanced technologies provide a path forward for foodborne virus detection, but
      more research and development will be needed to provide the level of
      manufacturing capacity required.

PMID- 29071197
TI  - Amplified visual immunosensor integrated with nanozyme for ultrasensitive
      detection of avian influenza virus.
AB  - Nanomaterial-based artificial enzymes or nanozymes exhibit superior properties
      such as stability, cost effectiveness and ease of preparation in comparison to
      conventional enzymes. However, the lower catalytic activity of nanozymes limits
      their sensitivity and thereby practical applications in the bioanalytical field.
      To overcome this drawback, herein we propose a very simple but highly sensitive,
      specific and low-cost dual enhanced colorimetric immunoassay for avian influenza
      A (H5N1) virus. 3,3',5,5'- Tetramethylbenzidine (TMBZ) was used as a reducing
      agent to produce gold nanoparticles (Au NPs) with blue colored solution from a
      viral target-specific antibody-gold ion mixture at first step. The developed blue
      color from the sensing design was further amplified through catalytic activity of
      Au NPs in presence of TMBZ-hydrogen peroxide (H2O2) solution in second step.
      Hence, the developed dual enhanced colorimetric immunosensor enables the
      detection of avian influenza virus A (H5N1) with a limit of detection (LOD) of
      1.11 pg/mL. Our results confirmed that the developed assay has superior
      sensitivity than the conventional ELISA method, plasmonic-based bioassay and
      commercial flu diagnostic kits. Proposed sensing method further showed its
      capability to detect viruses, avian influenza A (H4N6) and A (H9N2) virus, in
      blood samples with limit of detection of 0.0269 HAU and 0.0331 HAU respectively.

PMID- 29071199
TI  - Encapsulation of Inorganic Nanomaterials inside Virus-Based Nanoparticles for
      Bioimaging.
AB  - Virus-based nanoparticles (VNPs) can serve as containers for inorganic
      nanomaterials with excellent physical and chemical properties. Incorporation of
      nanomaterials inside the inner cavity of VNPs has opened up lots of possibilities
      for imaging applications in the field of biology and medicine. Encapsulation of
      inorganic nanoparticles (NPs) in VNPs can achieve the labeling of VNPs with
      nanoprobes and maintain the original outer surface features of VNPs at the same
      time. In return, VNPs enhance the stability and biocompatibility of the inorganic
      cargoes. This review briefly summarizes the current typical strategies to
      encapsulate inorganic nanomaterials in VNPs, i.e. mineralization and self
      assembly, as well as the applications of these hybrid nanostructures in the field
      of bioimaging, including in vitro and in vivo fluorescence imaging, magnetic
      resonance imaging, and theranostics. Nanophotonic studies based on the VNP
      platform are also discussed. We anticipate that this field will continue to
      flourish, with new exciting opportunities stemming from advancements in the
      rational design of VNPs, the development of excellent inorganic nanomaterials,
      the integration of multiple functionalities, and the regulation of nano-bio
      interfacial interactions.

PMID- 29071198
TI  - Be Active or Not: the Relative Contribution of Active and Passive Tumor Targeting
      of Nanomaterials.
AB  - Malignant tumor (cancer) remains as one of the deadliest diseases throughout the
      world, despite its overall mortality drops. Nanomaterials (NMs) have been widely
      studied as diagnostic and/or therapeutic agents for tumors. A feature of NMs,
      compared to small molecules, is that NMs can be concentrated passively in tumors
      through enhanced permeability and retention (EPR) effect. In the meantime, NMs
      can be engineered to target toward tumor specific markers in an active manner,
      e.g., receptor-mediated targeting. The relative contribution of the EPR effect
      and the receptor-mediated targeting to NM accumulation in tumor tissues has not
      been clearly defined yet. Here, we tackle this fundamental issue by reviewing
      previous studies. First, we summarize the current knowledge on these two tumor
      targeting strategies of NMs, and on how NMs arrive to tumors from blood
      circulation. We then demonstrate that contribution of the active and passive
      effects to total accumulation of NMs in tumors varies with time. Over time, the
      receptor-mediated targeting contributes more than the EPR effect with a ratio of
      3 in the case of urokinase-type plasminogen activator receptor (uPAR)-mediated
      targeting and human serum albumin (HSA)-mediated EPR effect. Therefore, this
      review highlights the dynamics of active and passive targeting of NMs on their
      accumulation at tumor sites, and is valuable for future design of NMs in cancer
      diagnosis and treatment.

PMID- 29071202
TI  - An Electrochemical Aptasensor Using Coaxial Capillary with Magnetic Nanoparticle,
      Urease Catalysis and PCB Electrode for Rapid and Sensitive Detection of
      Escherichia coli O157:H7.
AB  - The continuous outbreaks of foodborne diseases have drawn public attentions to
      food safety. Early screening of foodborne pathogens is crucial to prevent and
      control of foodborne diseases. In this study, a novel electrochemical aptasensor
      was developed for rapid and sensitive detection of E. coli O157:H7 using the
      coaxial capillary with immune magnetic nanoparticles (MNPs) for specific
      separation of the target bacteria, the urease with urea for amplification of the
      impedance signals, and the PCB gold electrode for measurement of the impedance
      change. The streptavidin modified MNPs were conjugated with the biotinylated
      polyclonal antibodies (PAbs) to form the immune MNPs, and captured in the coaxial
      capillary with the line-up high gradient magnetic fields to separate the bacteria
      from the large volume of sample. Then, the gold nanoparticles (GNPs) were
      modified with the aptamers against E. coli and the urease, and injected into the
      capillary to react with the bacteria and form the MNP-PAb-bacteria-aptamer-GNP
      urease complexes. Finally, the urease on the complexes was used to catalyze the
      hydrolysis of urea into ammonium ions and carbonate ions in the capillary,
      leading to the decrease in the impedance of the catalysate, which was measured by
      the gold plating PCB electrode. The impedance change of the catalysate and the
      concentration of the bacteria had a good linear relationship. This aptasensor was
      able to detect E. coli as low as 101 CFU/mL in 3 h, and the mean recovery of E.
      coli in the spiked pasteurized milk was ~99%. This proposed aptasensor has the
      potential for practical applications of foodborne pathogen detection due to its
      short detection time, high sensitivity and low cost.

PMID- 29071201
TI  - Nanomaterial-based Microfluidic Chips for the Capture and Detection of
      Circulating Tumor Cells.
AB  - Circulating tumor cells (CTCs), a type of cancer cells that spreads from primary
      or metastatic tumors into the bloodstream, can lead to a new fatal metastasis. As
      a new type of liquid biopsy, CTCs have become a hot pursuit and detection of CTCs
      offers the possibility for early diagnosis of cancers, earlier evaluation of
      chemotherapeutic efficacy and cancer recurrence, and choice of individual
      sensitive anti-cancer drugs. The fundamental challenges of capturing and
      characterizing CTCs are the extremely low number of CTCs in the blood and the
      intrinsic heterogeneity of CTCs. A series of microfluidic devices have been
      proposed for the analysis of CTCs with automation capability, precise flow
      behaviors, and significant advantages over the conventional larger scale systems.
      This review aims to provide in-depth insights into CTCs analysis, including
      various nanomaterial-based microfluidic chips for the capture and detection of
      CTCs based on the specific biochemical and physical properties of CTCs. The
      current developmental trends and promising research directions in the
      establishment of microfluidic chips for the capture and detection of CTCs are
      also discussed.

PMID- 29071200
TI  - Multiplexed Optical Imaging of Tumor-Directed Nanoparticles: A Review of Imaging
      Systems and Approaches.
AB  - In recent decades, various classes of nanoparticles have been developed for
      optical imaging of cancers. Many of these nanoparticles are designed to
      specifically target tumor sites, and specific cancer biomarkers, to facilitate
      the visualization of tumors. However, one challenge for accurate detection of
      tumors is that the molecular profiles of most cancers vary greatly between
      patients as well as spatially and temporally within a single tumor mass. To
      overcome this challenge, certain nanoparticles and imaging systems have been
      developed to enable multiplexed imaging of large panels of cancer biomarkers.
      Multiplexed molecular imaging can potentially enable sensitive tumor detection,
      precise delineation of tumors during interventional procedures, and the
      prediction/monitoring of therapy response. In this review, we summarize recent
      advances in systems that have been developed for the imaging of optical
      nanoparticles that can be heavily multiplexed, which include surface-enhanced
      Raman-scattering nanoparticles (SERS NPs) and quantum dots (QDs). In addition to
      surveying the optical properties of these various types of nanoparticles, and the
      most-popular multiplexed imaging approaches that have been employed,
      representative preclinical and clinical imaging studies are also highlighted.

PMID- 29071203
TI  - Maternal smoking and risk of obesity in school children: Investigating early life
      theory from the GRECO study.
AB  - Based on the Early Life Theory, maternal smoking may be a factor affecting child
      weight status, adiposity level and blood pressure later in life. The purpose of
      this study was primarily to examine the risk of maternal smoking during pregnancy
      with overweight and obesity, central and total adiposity in school children.
      Secondarily, to assess the effect of maternal smoking, with children's blood
      pressure (BP). Data from the Greek Childhood Obesity cross sectional study
      (GRECO), conducted from October 2008 to May 2009, were used. A total of 2400
      questionnaires gathered from children and their parents were analysed. Maternal
      and gestational data were gathered by a self-administered questionnaire. Women
      were categorized as non-smokers or smokers if they smoked >= 1 cigarettes/day
      during pregnancy. Children's body weight, height, waist circumference and BP were
      measured. Multiple logistic and linear regression analysis was conducted,
      adjusting for covariates. Four models were used in the process. The study found
      that children of maternal-smokers were more likely to be overweight or obese (OR:
      1.6 to 1.82) and to have a larger waist circumference (OR: 1.73 to 1.85),
      compared to children of non-smokers in all models used. Total fat percentage was
      not significantly associated with maternal smoking when adjusted. Systolic and
      diastolic BP was not associated with maternal smoking. Results of this study
      strengthen the need for smoking cessation during pregnancy in order to possibly
      reduce the childhood obesity epidemic. Creating public health awareness of the
      potential risk of maternal-smoking on children's weight status later in life is
      warranted.

PMID- 29071205
TI  - Disseminated paracoccidioidomycosis prediagnosticated as neoplasm: An important
      challenge in diagnosis using rt-PCR.
AB  - This paper presents a case of disseminated paracoccidioidomycosis in a 62-year
      old male patient, who lives in Belo Horizonte, MG, Brazil. The patient was
      hospitalized with icteric syndrome of cholestatic pattern and weight loss, with
      loss 30 kg in 5 months. The imaging of the abdomen showed lesion of infiltrative
      pattern, affecting gallbladder and intrahepatic bile ducts, suggesting neoplasia
      of malignant behavior, besides to presenting the yellow nail syndrome.
      Dermatological examination presented erythematous-infiltrated plaques in the
      occipital region. Also, the patient presented tegumentary lesions on the scalp
      and lumbar region from which the histopathological examination was carried out,
      which evidenced yeasts cells. The drug of choice for therapy was Liposomal
      Amphotericin-B. At the end of the antifungal treatment, liver enzyme dosages were
      normalized and there was improvement of the general condition of the patient, as
      well as the skin lesions. Here, we demonstrate the importance of molecular
      biology to confirm the diagnosis. Especially in cases of difficult diagnosis.

PMID- 29071204
TI  - Joint Attention and Early Social Developmental Cascades in Neurogenetic
      Disorders.
AB  - This review examines what is known about joint attention and early social
      development in three neurogenetic syndromes: Down syndrome, Williams syndrome,
      and fragile X syndrome. In addition, the potential cascading effects of joint
      attention on subsequent social development, especially social interaction and
      social cognition are proposed. The potential issues and complexities associated
      with conducting prospective, longitudinal studies of infant social development in
      neurogenetic disorders are discussed.

PMID- 29071206
TI  - Estrogen receptor beta exhibited anti-tumor effects on osteosarcoma cells by
      regulating integrin, IAP, NF-kB/BCL-2 and PI3K/Akt signal pathway.
AB  - This study aimed to investigate the effects of Estrogen receptor beta (ERbeta) on
      osteosarcoma cells, and explore the regulatory mechanisms involved in this
      process. Osteosarcoma U2-OS cells consisted four groups, and treated by E2, E2 +
      LY294002 (ERbeta agonists), E2 + ERbeta siRNA, E2 + ERbeta siRNA + LY294002,
      respectively. Cell counting kit 8 (CCK-8) assay was performed to detect the cell
      viability of U2-OS cells in each group. The effects of ERbeta on the migration
      and invasion ability of U2-OS cells were examined by wound healing assay and
      transwell cell culture chamber, respectively. The expression of Inhibitor of
      apoptosis protein (IAP) and integrin alpha5 in U2-OS cells of each group was
      detected by quantitative RT-PCR, and the expression of phosphorylated p65 (p
      p65), p-AKT and Bcl-2 was detected by western blotting. The cell viability,
      migration and invasion ability of U2-OS cells were significantly increased by
      ERbeta siRNA, but inhibited by ERbeta agonists LY294002 (p < 0.05). ERbeta siRNA
      significantly downregulated Integrin alpha5 and unregulated IAP in U2-OS cells (p
      < 0.05). The expression of p-p65, p-AKT and Bcl-2 was significantly reduced by
      LY294002, but increased by ERbeta siRNA (p < 0.05). In conclusion, ERbeta
      exhibited obvious anti-tumor effects on osteosarcoma cells by regulating
      integrin, IAP, NF-kBBCL-2 and PI3K/Akt signal pathway.

PMID- 29071207
TI  - Impaired prefrontal activity to regulate the intrinsic motivation-action link in
      schizophrenia.
AB  - A core feature of schizophrenia (SCZ) is impairment in intrinsic motivation.
      Although intrinsic motivation plays an important role in enhancing improvement of
      the social functioning, its neural mechanisms of impairment have yet to be
      clarified. We hypothesized that abnormal function of the frontostriatal loop
      consisting of the striatum and lateral prefrontal cortex (LPFC) may be related to
      impaired intrinsic motivation in SCZ. We tested this by comparing the brain
      activity measured by functional magnetic resonance imaging and behavioral
      parameters associated with movement, motivation, and cognitive control between 18
      stable SCZ patients and 17 healthy control (HC) participants during a task that
      elicits intrinsic motivation. We also compared the functional connectivity during
      resting-state and the fractional anisotropy using diffusion tensor imaging
      analysis between the two groups. We adopted an enjoyable timing task to stop a
      stopwatch at an exact time, which in our previous study has demonstrated to
      elicit intrinsic motivation. Although the performance level in general was not
      different between groups, the SCZ group performed worse than the HC group in
      trials following "overshoot" errors (i.e., the response was too late). SCZ
      participants showed lower intrinsic motivation to the task than the HC group in
      an inventory report. The striatal activity during the prediction at the task cue
      period was consistently lower in SCZ participants than in HC. The LPFC activity
      at the task cue period positively correlated with intrinsic motivation and also
      with the rate of success following overshoot errors in the HC group, but not in
      the SCZ group. The LPFC activity at the task cue period was also positively
      correlated with the striatal activity in both groups. The striatal activity
      during the feedback period was not significantly different between groups. These
      results suggest that, unlike HC, the neural activity in the LPFC fails to mediate
      between prediction of hedonic events and cognitive control of action plans in
      SCZ, whereas the hedonic response is retained.

PMID- 29071208
TI  - Fast progressive lower motor neuron disease is an ALS variant: A two-centre tract
      of interest-based MRI data analysis.
AB  - BACKGROUND: The criteria for assessing upper motor neuron pathology in pure lower
      motor neuron disease (LMND) still remain a major issue of debate with respect to
      the clinical classification as an amyotrophic lateral sclerosis (ALS) variant.
      OBJECTIVE: The study was designed to investigate white matter damage by a
      hypothesis-guided tract-of-interest-based approach in patients with LMND compared
      with healthy controls and 'classical' ALS patients in order to identify in vivo
      brain structural changes according to the neuropathologically defined ALS
      affectation pattern. Data were pooled from two previous studies at two different
      study sites (Ulm, Germany and Milano, Italy). METHODS: DTI-based white matter
      integrity mapping was performed by voxelwise statistical comparison and by a
      tractwise analysis of fractional anisotropy (FA) maps according to the ALS
      staging pattern for 65 LMND patients (clinically differentiated in fast and slow
      progressors) vs. 92 matched controls and 101 ALS patients with a 'classical'
      phenotype to identify white matter structural alterations. RESULTS: The analysis
      of white matter structural connectivity by regional FA reductions demonstrated
      the characteristic alteration patterns along the CST and also in frontal and
      prefrontal brain areas in LMND patients compared to controls and ALS. Fast
      progressing LMND showed substantial involvement, like in ALS, while slow
      progressors showed less severe alterations. In the tract-specific analysis
      according to the ALS-staging pattern, fast progressing LMND showed significant
      alterations of ALS-related tract systems as compared to slow progressors and
      controls. CONCLUSIONS: This study showed an affectation pattern for
      corticoefferent fibers in LMND with fast disease progression as defined for ALS,
      that way confirming the hypothesis that fast progressing LMND is a phenotypical
      variant of ALS.

PMID- 29071210
TI  - Identifying motor functional neurological disorder using resting-state functional
      connectivity.
AB  - BACKGROUND: Motor functional neurological disorder (mFND) is a clinical diagnosis
      with reliable features; however, patients are reluctant to accept the diagnosis
      and physicians themselves bear doubts on potential misdiagnoses. The
      identification of a positive biomarker could help limiting unnecessary costs of
      multiple referrals and investigations, thus promoting early diagnosis and
      allowing early engagement in appropriate therapy. OBJECTIVES: To test whether
      resting-state (RS) functional magnetic resonance imaging could discriminate
      patients suffering from mFND from healthy controls. METHODS: We classified 23
      mFND patients and 25 age- and gender-matched healthy controls based on whole
      brain RS functional connectivity (FC) data, using a support vector machine
      classifier and the standard Automated Anatomic Labeling (AAL) atlas, as well as
      two additional atlases for validation. RESULTS: Accuracy, specificity and
      sensitivity were over 68% (p = 0.004) to discriminate between mFND patients and
      controls, with consistent findings between the three tested atlases. The most
      discriminative connections comprised the right caudate, amygdala, prefrontal and
      sensorimotor regions. Post-hoc seed connectivity analyses showed that these
      regions were hyperconnected in patients compared to controls. CONCLUSIONS: The
      good accuracy to discriminate patients from controls suggests that RS FC could be
      used as a biomarker with high diagnostic value in future clinical practice to
      identify mFND patients at the individual level.

PMID- 29071211
TI  - Deep learning of joint myelin and T1w MRI features in normal-appearing brain
      tissue to distinguish between multiple sclerosis patients and healthy controls.
AB  - Myelin imaging is a form of quantitative magnetic resonance imaging (MRI) that
      measures myelin content and can potentially allow demyelinating diseases such as
      multiple sclerosis (MS) to be detected earlier. Although focal lesions are the
      most visible signs of MS pathology on conventional MRI, it has been shown that
      even tissues that appear normal may exhibit decreased myelin content as revealed
      by myelin-specific images (i.e., myelin maps). Current methods for analyzing
      myelin maps typically use global or regional mean myelin measurements to detect
      abnormalities, but ignore finer spatial patterns that may be characteristic of
      MS. In this paper, we present a machine learning method to automatically learn,
      from multimodal MR images, latent spatial features that can potentially improve
      the detection of MS pathology at early stage. More specifically, 3D image patches
      are extracted from myelin maps and the corresponding T1-weighted (T1w) MRIs, and
      are used to learn a latent joint myelin-T1w feature representation via
      unsupervised deep learning. Using a data set of images from MS patients and
      healthy controls, a common set of patches are selected via a voxel-wise t-test
      performed between the two groups. In each MS image, any patches overlapping with
      focal lesions are excluded, and a feature imputation method is used to fill in
      the missing values. A feature selection process (LASSO) is then utilized to
      construct a sparse representation. The resulting normal-appearing features are
      used to train a random forest classifier. Using the myelin and T1w images of 55
      relapse-remitting MS patients and 44 healthy controls in an 11-fold cross
      validation experiment, the proposed method achieved an average classification
      accuracy of 87.9% (SD = 8.4%), which is higher and more consistent across folds
      than those attained by regional mean myelin (73.7%, SD = 13.7%) and T1w
      measurements (66.7%, SD = 10.6%), or deep-learned features in either the myelin
      (83.8%, SD = 11.0%) or T1w (70.1%, SD = 13.6%) images alone, suggesting that the
      proposed method has strong potential for identifying image features that are more
      sensitive and specific to MS pathology in normal-appearing brain tissues.

PMID- 29071213
TI  - Cycles of judicial and executive power in irregular migration.
AB  - This article argues that power struggles between judiciaries and executives are
      fuelled by tensions of securitisation, border control and human rights over the
      issue of irregular migration. The article juxtaposes three paradigm court cases
      to render the argument concrete, focusing on two Australian High Court decisions
      (M70 v Minister for Immigration and Citizenship and CPCF v. Minister for
      Immigration and Border Protection & Anor) and one decision from the European
      Court of Human Rights (Hirsi Jamaa and Others v. Italy). An examination of these
      cases reveals each step of this cycle: the executive attempts to produce a buffer
      to avoid or minimise migrants' protections and judicial review, yet such
      manoeuvring is countered by the judges. Following this, new steps of the cycle
      occur: governments display disappointment to courts' interventions in an effort
      to discredit the exercise of judicial power while the judiciaries maintain the
      focus on the rule of law. And so the cycle continues. The key argument of this
      paper rests on the paradox resulting from the executive's attempts to curb
      judicial intervention, because such attempts actually empower judiciaries.
      Comparing different jurisdictions highlights how this cyclical power struggle is
      a defining element between these two arms of power across distinct legal
      geographical boundaries. By tracing this development in Australia and in Europe,
      this article demonstrates that the argument has global significance.

PMID- 29071214
TI  - A protocol for preparation and transfection of rat entorhinal cortex organotypic
      cultures for electrophysiological whole-cell recordings.
AB  - Understanding how neuromodulators influence synaptic transmission and intrinsic
      excitability within the entorhinal cortex (EC) is critical to furthering our
      understanding of the molecular and cellular aspects of this region. Organotypic
      cultures can provide a cost-effective means to employ selective molecular
      biological strategies in elucidating cellular mechanisms of neuromodulation in
      the EC. We therefore adapted our acute slice model for organotypic culture
      applications and optimized a protocol for the preparation and biolistic
      transfection of cultured horizontal EC slices. Here, we present our detailed
      protocol for culturing EC slices. Using an n-methyl-d-glucamine (NMDG)-containing
      cutting solution, we obtain healthy EC slice cultures for electrophysiological
      recordings. We also present our protocol for the preparation of "bullets"
      carrying one or more constructs and demonstrate successful transfection of EC
      slices. We build upon previous methods and highlight specific aspects in our
      method that greatly improved the quality of our results. We validate our methods
      using immunohistochemical, imaging, and electrophysiological techniques. The
      novelty of this method is that it provides a description of culturing and
      transfection of EC neurons for specifically addressing their functionality. This
      method will enable researchers interested in entorhinal function to quickly adopt
      a similar slice culture transfection system for their own investigations.

PMID- 29071212
TI  - The use of port-a-caths in adult patients with Lysosomal Storage Disorders
      receiving Enzyme Replacement Therapy-one centre experience.
AB  - Port-a-cath is a widely used device in patients with long-term venous access
      demand such as frequent or continuous administration of medications such as
      Enzyme Replacement Therapy (ERT), chemotherapy delivery, blood transfusions,
      blood products, and fluids. Patients with Lysosomal Storage Diseases (LSDs) often
      require recurrent courses of ERT. We reviewed our experience of using port-a
      caths in patients with LSDs with the focus on challenges and complications
      associated with these catheters. Among 245 adult patients who were treated with
      ERT, twenty patients (8.2%) had a port-a-cath inserted due to poor venous access.
      Six patients were using their first port whereas five other patients had their
      port-a-caths replaced at least once. The remaining six patients had inactive port
      a-caths. The majority of patients with active port-a-caths never missed more than
      one consecutive infusion, although one patient missed 2 consecutive infusions
      whilst on holiday. We identified significant gaps in patients' and their
      families' understanding of the management of port-a-caths and risks associated
      with them. It resulted in producing a leaflet and designing an educational
      program for our LSD patients.

PMID- 29071209
TI  - How changes in brain activity and connectivity are associated with motor
      performance in people with MS.
AB  - People with multiple sclerosis (MS) exhibit pronounced changes in brain
      structure, activity, and connectivity. While considerable work has begun to
      elucidate how these neural changes contribute to behavior, the heterogeneity of
      symptoms and diagnoses makes interpretation of findings and application to
      clinical practice challenging. In particular, whether MS related changes in brain
      activity or brain connectivity protect against or contribute to worsening motor
      symptoms is unclear. With the recent emergence of neuromodulatory techniques that
      can alter neural activity in specific brain regions, it is critical to establish
      whether localized brain activation patterns are contributing to (i.e.
      maladaptive) or protecting against (i.e. adaptive) progression of motor symptoms.
      In this manuscript, we consolidate recent findings regarding changes in
      supraspinal structure and activity in people with MS and how these changes may
      contribute to motor performance. Furthermore, we discuss a hypothesis suggesting
      that increased neural activity during movement may be either adaptive or
      maladaptive depending on where in the brain this increase is observed.
      Specifically, we outline preliminary evidence suggesting sensorimotor cortex
      activity in the ipsilateral cortices may be maladaptive in people with MS. We
      also discuss future work that could supply data to support or refute this
      hypothesis, thus improving our understanding of this important topic.

PMID- 29071216
TI  - Effects of Resveratrol on the Structure and Catalytic Function of Bovine Liver
      catalase (BLC): Spectroscopic and Theoretical Studies.
AB  - Purpose: The study on the interaction between various compounds and
      macromolecules such as enzymes has been very important for monitoring the
      alteration of structural and functional properties of them. Resveratrol (3, 5, 4
      trihydroxy-stilbene; RES) is a biologically active phytoallexin found in grapes
      and other food products. This article shows an interaction of native bovine liver
      catalase (BLC) with natural antioxidant product, trans resveratrol (tRES) using
      multispectroscopic methods. Methods: The interaction between BLC and tRES is
      performed using UV-vis absorption, fluorescence and circular dichroism (CD)
      spectroscopy and molecular docking study. Results: In vitro kinetic studies
      indicated that tRES can decrease BLC activity through uncompetitive inhibition.
      The results of spectroscopic methods represented that the binding of tRES with
      BLC can change the micro-region around aromatic amino acids (tryptophan (Trp) and
      tyrosine (Tyr)) and quench intrinsic fluorescence of BLC by a static mechanism.
      According to fluorescence quenching data analysis, it was revealed that tRES has
      one binding site on BLC. The thermodynamic parameters were obtained, which
      demonstrated that tRES can bind to BLC by van der Waals forces and hydrogen
      bonds. Molecular docking results indicated that tRES binds to BLC away from heme
      group and near to the Tyr 324 and Phe 265. These results are in agreement with
      the experimental results. Conclusion: The inhibitory effect of tRES on BLC
      demonstrated that excessive consumption of the antioxidants could be resulted in
      hazardous effects.

PMID- 29071215
TI  - The Different Mechanisms of Cancer Drug Resistance: A Brief Review.
AB  - Anticancer drugs resistance is a complex process that arises from altering in the
      drug targets. Advances in the DNA microarray, proteomics technology and the
      development of targeted therapies provide the new strategies to overcome the drug
      resistance. Although a design of the new chemotherapy agents is growing quickly,
      effective chemotherapy agent has not been discovered against the advanced stage
      of cancer (such as invasion and metastasis). The cancer cell resistance against
      the anticancer agents can be due to many factors such as the individual's genetic
      differences, especially in tumoral somatic cells. Also, the cancer drug
      resistance is acquired, the drug resistance can be occurred by different
      mechanisms, including multi-drug resistance, cell death inhibiting (apoptosis
      suppression), altering in the drug metabolism, epigenetic and drug targets,
      enhancing DNA repair and gene amplification. In this review, we outlined the
      mechanisms of cancer drug resistance and in following, the treatment failures by
      common chemotherapy agents in the different type of cancers.

PMID- 29071218
TI  - Melatonin and N- Acetylcysteine as Remedies for Tramadol-Induced Hepatotoxicity
      in Albino Rats.
AB  - Purpose: The therapeutic benefit derived from the clinical use of tramadol (TD)
      has been characterized by hepatotoxicity due to misuse and abuse. The
      implications of drug-induced hepatotoxicity include socio-economic burden which
      makes the search for remedy highly imperative. The present study investigated the
      protective effects of melatonin (MT) and n-acetylcysteine (NAC) on TD-induced
      hepatotoxicity in albino rats. Methods: Forty five adult rats used for this study
      were divided into nine groups of five rats each. The rats were pretreated with
      10mg/kg/day of NAC, 10mg/kg/day of MT and combined doses of NAC and MT prior to
      the administration of 15 mg/kg/day of TD intraperitoneally for 7 days
      respectively. At the termination of drug administration, rats were weighed,
      sacrificed, and serum was extracted and evaluated for liver function parameters.
      The liver was harvested, weighed and evaluated for oxidative stress indices and
      liver enzymes. Results: Alanine aminotransferase, alkaline phosphatase, aspartate
      aminotransferase, total bilirubin, conjugated bilirubin, and malondialdehyde
      levels were significantly (P<0.05) increased in rats administered with TD when
      compared to control. Furthermore, glutathione, superoxide dismutase and catalase
      levels were decreased significantly (P<0.05) in rats administered with TD when
      compared to control. The Liver of TD-treated rats showed necrosis of hepatocytes.
      However, the observed biochemical and liver histological alterations in TD
      treated rats were attenuated in NAC and MT pretreated rats. Interestingly,
      pretreatment with combined doses of NAC and MT produced significant (P<0.05)
      effects on all evaluated parameters in comparison to their individual doses.
      Conclusion: Based on the findings in this study, melatonin and n- acetylcysteine
      could be used clinically as remedies for tramadol associated hepatotoxity.

PMID- 29071217
TI  - Modafinil Improves Catalepsy in a Rat 6-Hydroxydopamine Model of Parkinson's
      Disease; Possible Involvement of Dopaminergic Neurotransmission.
AB  - Purpose: Modafinil is a vigilance-enhancing drug licensed for narcolepsy. The use
      of modafinil leads to various neuromodulatory effects with very low abuse
      potential. A body of evidence suggested that modafinil may have anti-parkinsonian
      effects. This study was designed to evaluate whether modafinil could improve
      motor dysfunction in the 6-hydroxydopamine (6-OHDA)-induced rat model of
      Parkinson's disease. Methods: Male Wistar rats (180-220 g, n= 98) were used in
      this study. Parkinsonism was induced by injection of 6-hydroxydopamine (10
      MUg/2MUl in 0.2 % ascorbic acid-saline) into the right striatum. Parkinsonian
      rats received intraperitoneal (ip) injections of modafinil (50, 75, and 100
      mg/kg) and catalepsy-like immobility was assessed by the bar test (BT).
      Furthermore, involvement of dopamine D1 and D2 receptors in modafinil's anti
      parkinsonian effects was studied. For this purpose, parkinsonian animals were
      pretreated with SCH23390 and raclopride (the dopamine D1 and D2 receptor
      anatgonists, respectively) or SCH23390 + raclopride, and then assessed by the BT.
      Results: Modafinil (100 mg/kg) showed anti-cataleptic effects in the BT. Notably,
      the effect of modafinil in the BT was reversed in parkinsonian rats pretreated
      with raclopride (1.25 mg/kg) and/or SCH23390 + raclopride (0.75 and 1.25 mg/kg,
      respectively), but not in those pretreated with SCH23390 (0.75 mg/kg).
      Conclusion: Acute administration of modafinil improves 6-OHDA-induced motor
      impairment possibly through activation of dopamine D2 receptors.

PMID- 29071219
TI  - Two Active Compounds from Caesalpinia sappan L. in Combination with Cisplatin
      Synergistically Induce Apoptosis and Cell Cycle Arrest on WiDr Cells.
AB  - Purpose: The aim of this study is to observe the synergistic effect of two active
      compounds of secang, brazilin and brazilein, combined with cisplatin on WiDr
      colon cancer cells. Methods: Cytotoxic activities of brazilin (Bi) and brazilein
      (Be) in single and in combination with cisplatin (Cisp) were examined by MTT
      assay. Synergistic effect was analyzed by combination index (CI) parameter.
      Apoptosis and cell cycle profiles were observed by using flow cytometry. Results:
      The result of MTT assay showed that IC50 value of brazilin and brazilein on WiDr
      cancer cells were 41 uM and 52 uM respectively. The combination of 1/2 IC50 of Bi
      Cisp reduced cells viability up to 64% and showed synergistic effect with CI
      value less than 1 (CI = 0.8). The combinations of 1/2 IC50 of Be-Cisp also
      reduced cells viability up to 78% and showed synergistic effect (CI=0.65).
      Combination of Bi-Cisp and Be-Cisp induced apoptosis higher than the single
      treatments. Further analysis on the cell cycle progression showed that single
      treatment of 1/2 IC50 of Be and Bi induced S-phase and G2/M-phase accumulation,
      while combination of Be-Cisp and Bi-Cisp enhanced S-phase accumulation.
      Conclusion: Both combination of Bi-Cisp and Be-Cisp showed synergistic effect on
      WiDr cells through induction of apoptosis and halted the cell cycle progression,
      thus, WiDr cells growth were significantly reduced.

PMID- 29071220
TI  - The Cytotoxic and Apoptotic Effects of Scrophularia Atropatana Extracts on Human
      Breast Cancer Cells.
AB  - Purpose: Breast cancer is the most frequent malignancy diagnosed in women both in
      developed and developing countries. Natural products especially those from herbal
      origin have high potential in producing drug components with a source of novel
      structures. The present study was designed to explore the cytotoxic effects and
      the cell death mechanism of Scrophularia atropatana extracts. Methods: MTT assay
      was employed to evaluate the cytotoxic activity of the extracts of S. atropatana
      on the MCF-7 as well as non-malignant cells. Furthermore, induction of apoptosis
      was evaluated by TUNEL assay, cell death detection ELISA, DNA fragmentation test,
      western blotting and Real Time PCR. Results: In vitro exposures of the MCF-7
      cells with different concentration of S. atropatana extract significantly
      inhibited their growth and viability and induced apoptosis in the MCF-7 cells.
      Cleavage PARP protein, decrease in the mRNA expression levels of bcl-2 and
      increase expression of Caspase-3 and Caspase-9 mRNA, highlights that the
      induction of apoptosis was the main mechanism of cell death. Moreover the
      expression study of Caspase-9 mRNA showed that, the extracts have induced
      apoptosis via intrinsic mitochondrial pathway. Conclusion: Our results
      demonstrated that dichloromethane extract of Scrophularia atropatana has an
      apoptotic effects and it can be developed as anticancer agents.

PMID- 29071221
TI  - Evaluating Adherence of Health-Care Team to Standard Guideline of Colistin Use at
      Intensive Care Units of a Referral Hospital in Shiraz, Southwest of Iran.
AB  - Purpose: To evaluate colistin use according to global standard drug consumption
      in intensive care units of a referral hospital in Shiraz, Iran Methods: A
      prospective, interventional study was performed during an 11 month period on 100
      patients admitted to ICUs of a teaching hospital being treated with colistin for
      at least 3 subsequent doses. Required demographic, clinical, and paraclinical
      data were gathered by a pharmacist. Fifteen indexes were considered to evaluate
      colistin use. A clinical pharmacist reviewed indication and dose of colistin at
      the time of prescribing this agent. Results: In our study population, pneumonia
      (69%) was the main indication of colistin. In 87% of patients, colistin
      administration was based on microbiological laboratory evidence. Continuation of
      therapy was inappropriate in 5% of cases. By the intervention of the clinical
      pharmacist, colistin was discontinued in all patients in whom empirical therapy
      was continued incorrectly. None of the patients received loading dose of
      colistin. The maintenance dose, dose interval, and duration of treatment of
      colistin were appropriate in 76%, 71%, and 100% of patients, respectively. For
      none of the patients, the pharmacokinetic dosing method was used. In all
      patients, serum creatinine and WBC count were evaluated on daily basis. The sum
      indexes of colistin use were relevant to standard guidelines in 67.33% of the
      cases. Conclusion: The results of this study highlight the necessity of the
      pharmaceutical care team participation in all stages of treatment with
      antibiotics. After pharmacist interventions, some criteria of colistin
      utilization were corrected and brought closer to standard values.

PMID- 29071222
TI  - Pharmaceutical Cocrystal of Piroxicam: Design, Formulation and Evaluation.
AB  - Purpose: Cocrystallisation of drug with coformers is a promising approach to
      alter the solid sate properties of drug substances like solubility and
      dissolution. The objective of the present work was to prepare, formulate and
      evaluate the piroxicam cocrystal by screening various coformers. Methods:
      Cocrystals of piroxicam were prepared by dry grinding method. The melting point
      and solubility of crystalline phase was determined. The potential cocrystal was
      characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility
      and dissolution rate were also evaluated. Orodispersible tablets of piroxicam
      cocrystal were formulated, optimized and evaluated using 32 factorial design.
      Results: Cocrystals of piroxicam-sodium acetate revealed the variation in melting
      points and solubility. The cocrystals were obtained in 1:1 ratio with sodium
      acetate. The analysis of Infrared explicitly indicated the shifting of
      characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted
      the crystallinity of cocrystals and noteworthy difference in 2theta value of
      intense peaks. Differential scanning calorimetry spectra of cocrystals indicated
      altered endotherms corresponding to melting point. The pH solubility profile of
      piroxicam showed sigmoidal curve, which authenticated the pKa-dependent
      solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile.
      The cocrystals exhibited faster dissolution rate owing to cocrystallization as
      evident from 30% increase in the extent of dissolution. The orodispersible
      tablets of piroxicam cocrystals were successfully prepared by direct compression
      method using crosscarmelose sodium as superdisintegrant with improved
      disintegration time (30 sec) and dissolution rate. Conclusion: The piroxicam
      cocrystal with modified properties was prepared with sodium acetate and
      formulated as orodispersible tablets having faster disintegration and greater
      dissolution rate.

PMID- 29071223
TI  - An Alignment-Independent 3D-QSAR Study of FGFR2 Tyrosine Kinase Inhibitors.
AB  - Purpose: Receptor tyrosine kinase (RTK) inhibitors are widely used
      pharmaceuticals in cancer therapy. Fibroblast growth factor receptors (FGFRs) are
      members of RTK superfamily which are highly expressed on the surface of carcinoma
      associate fibroblasts (CAFs). The involvement of FGFRs in different types of
      cancer makes them promising target in cancer therapy and hence, the
      identification of novel FGFR inhibitors is of great interest. In the current
      study we aimed to develop an alignment independent three dimensional quantitative
      structure-activity relationship (3D-QSAR) model for a set of 26 FGFR2 kinase
      inhibitors allowing the prediction of activity and identification of important
      structural features for these inhibitors. Methods: Pentacle software was used to
      calculate grid independent descriptors (GRIND) for the active conformers
      generated by docking followed by the selection of significant variables using
      fractional factorial design (FFD). The partial least squares (PLS) model
      generated based on the remaining descriptors was assessed by internal and
      external validation methods. Results: Six variables were identified as the most
      important probes-interacting descriptors with high impact on the biological
      activity of the compounds. Internal and external validations were lead to good
      statistical parameters (r2 values of 0.93 and 0.665, respectively). Conclusion:
      The results showed that the model has good predictive power and may be used for
      designing novel FGFR2 inhibitors.

PMID- 29071225
TI  - Nanoparticles of Chitosan Loaded Ciprofloxacin: Fabrication and Antimicrobial
      Activity.
AB  - Purpose: Chitosan is a natural mucoadhesive polymer with antibacterial activity.
      In the present study, chitosan (CS) nanoparticles were investigated as a vehicle
      for delivery of antibiotic, ciprofloxacin hydrochloride. Methods: Ionotropic
      gelation method was used for preparation chitosan nanoparticles. The effects of
      various factors including concentration of CS, concentration of tripolyphosphate
      (TPP), and homogenization rate on the size of nanoparticles were studied. The
      effects of various mass ratios of CS to ciprofloxacin hydrochloride on the
      encapsulation efficiency of nanoparticles were assessed. Results: The particles
      prepared under optimal condition of 0.45% CS concentration, 0.45% TPP
      concentration and homogenizer rate at 6000 rpm, had 72 nm diameter. In these
      particles with 1:0.5 mass ratio of CS to ciprofloxacin hydrochloride, the
      encapsulation efficiency was 23%. The antibacterial activity of chitosan
      nanoparticles and ciprofloxacin-loaded nanoparticles against E.coli and S.aureus
      was evaluated by calculation of minimum inhibitory concentration (MIC). Results
      showed that MIC of ciprofloxacin loaded chitosan nanoparticles was 50% lower than
      that of ciprofloxacin hydrochloride alone in both of microorganism species.
      Nanoparticles without drug exhibited antibacterial activity at higher
      concentrations and MIC of them against E.coli and S.aureus was 177 and 277 ug/ml,
      respectively. Conclusion: Therefore chitosan nanoparticles could be applied as
      carrier for decreasing the dose of antibacterial agents in the infections.

PMID- 29071224
TI  - Process, Physicochemical Characterization and In-Vitro Assessment of Albendazole
      Microcrystals.
AB  - Purpose: Albendazole is a poorly soluble drug which limits its oral
      bioavailability. The study was focussed to enhance the solubility by in-situ
      micronization. Methods: Albendazole microcrystals were prepared by solvent change
      method using gum karaya and hupu gum as stabilizing agents and the effect of each
      stabilizer on the prepared microcrystals were studied. FT-IR, DSC, XRD and SEM
      analysis were performed as a part of characterization studies. The formulations
      were evaluated for micromeritics, solubility and drug release. The microcrystals
      that had shown optimized properties were filled into suitable capsules. Results:
      The formulations showed reduction in particle size with uniform size distribution
      and three folds increase in drug release. The microcrystals had shown more than
      100-folds increase in solubility compared to pure drug. Surface energy, enthalpy
      and crystalline nature of microcrystals were found to be reduced. Microcrystals
      containing gum karaya had shown more drug release. The filled-in capsules also
      showed increase in drug release rate. The solubility enhancement of albendazole
      microcrystals was mainly due to the surface adsorption of the stabilizing agents
      that led to reduction in surface energy and crystalline nature as substantiated
      by the DSC and XRD studies. The type of stabilizing agent had significant effect
      on dissolution rate. High affinity of albendazole with gum karaya led to faster
      drug release profiles. Conclusion: The study proved that in-situ micronization is
      an effective technique to enhance the solubility and dissolution rate of poorly
      soluble drugs like albendazole.

PMID- 29071226
TI  - Pharmacological Properties of Vochysia Haenkeana (Vochysiaceae) Extract to
      Neutralize the Neuromuscular Blockade Induced by Bothropstoxin-I (Lys49
      Phospholipase A2) Myotoxin.
AB  - Purpose: Bothrops snakes are responsible for more than 70 % of snakebites every
      year in Brazil and their venoms cause severe local and systemic damages. The
      pharmacological properties of medicinal plants have been widely investigated in
      order to discover new alternative treatments for different classes of diseases
      including neglected tropical diseases as envenomation by snakebites. In this
      work, we have investigated the ability of Vochysia haenkeana stem barks extract
      (VhE) to neutralize the neuromuscular effects caused by Bothropstoxin-I (BthTX
      I), the major phospholipase A2 (PLA2) myotoxin from B. jararacussu venom.
      Methods: The biological compounds of VhE were analysed under thin layer
      chromatography (TLC) and its neutralizing ability against BthTX-I was assessed
      through twitch-tension recordings and histological analysis in mouse phrenic
      nerve-diaphragm (PND) preparations. The antimicrobial activity of VhE was
      assessed against S. aureus, E. coli and P. aeruginosa strains. The aggregation
      activity of VhE was analysed under protein precipitation assay. Results: VhE
      showed the presence of phenolic compound visualized by blue trace under TLC. VhE
      abolished the neuromuscular blockade caused by BthTX-I applying the pre-toxin
      incubation treatment and partially neutralized the BthTX-I action under post
      toxin incubation treatment; VhE contributed slightly to decrease the myotoxicity
      induced by BthTX-I. The neutralizing mechanism of VhE may be related to protein
      aggregation. VhE showed no antimicrobial activity. Conclusion: V. haenkeana
      extract which has no antimicrobial activity exhibited neutralizing ability
      against the neuromuscular blockade caused by BthTX-I and also contributed to
      decrease its myotoxicity. Protein aggregation involving phenolic compounds may be
      related in these protective effects.

PMID- 29071227
TI  - Formulation and Optimization of Oral Mucoadhesive Patches of Myrtus Communis by
      Box Behnken Design.
AB  - Purpose: Recurrent aphthous stomatitis (RAS) is the most common painful
      ulcerative disease of oral mucosa happening in ~20% of people. Aimed to develop
      Myrtus communis L. (Myrtle) containing oral patches, we applied box-behnken
      design to evaluate the effect of polymers such as Polyvinyl pyrrolidone (PVP),
      Gelatin, Methylcellulose (MC) and Pectin. Methods: The patches properties such as
      tensile strength, folding endurance, swelling index, thickness, mucoadhesive
      strength and the pattern of myrtle release were evaluated as dependent variables.
      Then, the model was adjusted according to the best fitted equation with box
      behnken design. Results: The results indicated that preparation of myrtle patch
      with hydrophilic polymers showed the disintegration time up to 24h and more.
      Using of polyvinyl pyrrolidone as a water soluble polymer and a pore-former
      polymer led to faster release of soluble materials from the patch to 29 (min-1).
      Also it decreases swelling index by increasing the patch disintegration. Gelatin
      and Pectin, with rigid matrix and water interaction properties, decreased the
      swelling ratio. Pectin increased the tensile strength, but gelatin produced an
      opposite effect. Thinner Myrtle patch (about 28um) was obtained by formulation of
      methyl cellulose with equal ratio with polyvinyl pyrrolidone or gelatin.
      Conclusion: Altogether, the analysis showed that the optimal formulation was
      achieved with of 35.04 mg of Gelatin, 7.22 mg of Pectin, 7.20 mg of polyvinyl
      pyrrolidone, 50.52 mg of methyl cellulose and 20 mg of Myrtle extract.

PMID- 29071229
TI  - Pantoprazole Sodium Loaded Microballoons for the Systemic Approach: In Vitro and
      In Vivo Evaluation.
AB  - Purpose: Various floating and pulsatile drug delivery systems suffer from
      variations in the gastric transit time affecting the bioavailability of drugs.
      The objective of the study was to develop Pantoprazole Sodium (PAN) microballoons
      that may prolong the gastric residence time and could enhance the drug
      bioavailability. Methods: Microballoons were prepared using Eudragit(r)L100 by
      adopting emulsion solvent diffusion method with non-effervescent approach, in
      vitro studies were performed and the in vivo evaluation was carried out employing
      ethanol induced ulceration method. Optimization and validation were carried out
      through Design Expert(r) software. Results: The results demonstrate an increase
      in percentage yield, buoyancy, encapsulation efficacy and swelling. Particles
      were in the size range 80-100 um following zero order release pattern. SEM study
      revealed their rough surface with spherical shape, internal cavity and porous
      walls. DSC thermo gram confirms the encapsulation of drug in amorphous form.
      Significant anti ulcer activity was observed for the prepared microballoons. The
      calculated ulcer index and protection were 0.20+/-0.05 and 97.43 % respectively
      for LRS-O (optimized formulation). Conclusion: This kind of pH dependent drug
      delivery may provide an efficient dosage regimen with enhanced patient
      compliance.

PMID- 29071228
TI  - Assay of Desmopressin Acetate in Nasal Spray: Development of Validated Pre Column
      HPLC-Fluorescence Method.
AB  - Purpose: Desmopressin acetate (DDAPV), a synthetic analogue of vasopressin, has
      been recommended to be used in diabetes insipidus, mild forms of hemophilia and
      Von Willebrand disease. The DDAPV is available for adminstration via different
      routes viz. oral, parenteral and nasal, however its dose is very less in case of
      nasal sprays (20 ug) and parenteral route (4 ug) compared to oral route (0.1 to
      0.3 mg in tablet). A sensitive and selective method is needed to be developed and
      validated for assay of low concentrations of DDAPV in its pharmaceutical dosage
      form i.e. nasal spray. Methods: Simple and specific HPLC-Fluorescecne method has
      been proposed for the quantitation of DDAPV at nanogram level in nasal
      formulations for the first time. DAPV, DDAPV EP impurity-B, chlorobutanol,
      benzalkonoium chloride were successfully derivatised with Ortho-Phthalaldehyde
      (OPA) and co-eluted on a C8 (50*2.1 mm, 3.5 um particle size, 120A) with mobile
      phase composed of 0.1% trifluroacetic acid, acetonitrile and Isopropyl alcohol in
      ratio of 70:25:5. The emission was measured at 450nm and flow rate was 0.8ml/min.
      The reaction was optimized in the terms of pH, stability of formed fluorophore
      and time consumed during the reaction. Results: The maximal fluorescence
      intensity was reached when the solutions were mixed for 3 min, and remained
      constant for at least 30 min at 20-25oC. The calibration curve was found linear
      from 50 to 5000 ng/ml with weight of 1/X2. The limit of detection was 10ng/ml and
      precision was less than 2.0. Conclusion: The developed HPLC-fluorescence assay
      method was successfully applied for quantitation of DDAPV in nasal spray. HPLC
      Fluorescence method was specific, sensitive, precise and accurate for
      determination of DDAPV. The method was able to quantify DDAPV at 50ng/ml with
      sufficient accuracy and precision. The validated HPLC-Fluorescence was
      successfully applied.

PMID- 29071230
TI  - The Effectiveness of a Pharmaceutical Care Model on Adherence to Antiretroviral
      Therapy: A SAME-Based Cohort Study in Brazil.
AB  - Purpose: To verify the effectiveness of a pharmaceutical care model developed by
      the Specialized Municipal Assistance Service in Sorocaba, Brazil, on adherence to
      ART among patients infected with HIV. Methods: A cohort study compared adherence
      to ART in two groups of patients: intervention group (patients assisted with
      pharmaceutical care, n=130) and non-intervention group (patients attended by the
      habitual dispensing process, n=229). Antiretroviral adherence was measured by the
      number of pharmacy refill records in a six-month period. The relationship between
      the use of other drugs for the treatment of opportunistic infections and the
      adherence rate in the intervention group and the correlation between adherence
      and viral load and CD4 lymphocytes were also assessed. Results: Higher adherence
      rates were observed in the intervention group (p<0.05). The use of others drugs
      did not influence adherence to ART (p=0.30). There was a positive correlation
      between adherence and the percentage of patients in the intervention group with
      undetectable viral loads (p=0.0004) and higher levels of CD4 lymphocytes
      (p=0.0024). Conclusion: The pharmaceutical care model developed by the SAME
      improved patient adherence to ART as well as clinical outcomes.

PMID- 29071231
TI  - Melanogenesis Inhibitory and Antioxidant Effects of Camellia oleifera Seed Oil.
AB  - Purpose: The study aimed to characterize the fatty acid profile of Camellia
      oleifera (tea) seed oil and evaluate for cytotoxicity and activities on
      melanogenesis and antioxidant activity assays in order to utilize as the
      functional oil. Methods: The fatty acid profile of oil was analyzed by gas
      chromatography/mass spectrometry (GC/MS). The cytotoxicity was performed by
      sulforhodamine B (SRB) assay in B16-F10 melanoma cells and 3T3-L1 cells. The
      melanogenesis assay, including melanin content and activities of tyrosinase and
      tyrosinase-related protein-2 (TRP-2), and antioxidant activity were evaluated.
      Results: Three major fatty acids of oil were oleic acid (87.93+/-0.19%), stearic
      (5.14+/-0.06%) and palmitic (5.08+/-0.12%) acids. The non-cytotoxicity of 5% tea
      seed oil demonstrated the cell viabilities of 94.59+/-3.41% in B16-F10 melanoma
      cells and 97.57+/-1.62% in 3T3-L1 cells. Tea seed oil exhibited the inhibitory
      activity on melanogenesis assay via inhibition of tyrosinase and TRP-2
      activities. The antioxidant activity of 3% tea seed oil appeared the cellular
      protection with cell viability of 90.38+/-7.77%. Conclusion: The results of study
      have shown the potential utilization of tea seed oil as the functional oil in
      several products, including health, food and cosmetic products.

PMID- 29071232
TI  - Vancomycin Capped with Silver Nanoparticles as an Antibacterial Agent against
      Multi-Drug Resistance Bacteria.
AB  - Purpose: Many antimicrobial medications are available to combat infections.
      However, the indiscriminate use of antibiotics has produced antibiotic resistance
      in the case of many bacterial pathogens. This study focuses on the development of
      nanoparticles (NPs) that enhance the in vitro antibiotic activity of vancomycin
      against multi-drug resistant (MDR) organisms. Methods: Spherical shaped
      thioglycolic acid-stabilized silver nanoparticles (TGA-AgNPs) were prepared by
      using a simple chemical reduction method. Then, vancomycin was conjugated to the
      terminal carboxyl of TGA in the presence of N-Hydroxysuccinimide (NHS) and N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC). Afterwards, the
      antibacterial activity of these nanoconjugates was examined by using the minimum
      inhibitory concentration (MIC) assay against MDR bacteria. Results: The rate of
      vancomycin bound to the AgNPs was 19.6%. The MIC values of vancomycin (Van)
      capped AgNPs against tested pathogens were in the range of (3.2, 1.6, 0.8, 0.4,
      0.2, 0.1, 0.05, and 0.025 ul/ml). The MIC was 0.1 ug/ml for VRE, MIC<=0.02 ug/ml
      for MRSE, and 0.05 ug/ml for S. aureus. The MIC corresponded to the MBC for all
      bacterial species. Conclusion: This study indicated that some antimicrobial
      agents like vancomycin can be conjugated with AgNPs. This can lead to increased
      antimicrobial activity against MDR microorganisms.

PMID- 29071233
TI  - Effect of Addition of Antifungal Agents on Physical and Biological Properties of
      a Tissue Conditioner: An In-Vitro Study.
AB  - Purpose: Tissue conditioners are used for healing of abused oral tissues. They
      may harbour microorganisms causing oral diseases such as candidiasis compromising
      the health of the patient. Also, addition of antifungal agents into tissue
      conditioner may alter its properties. This study compares the anti-fungal
      property and mechanical properties of tissue conditioner containing different
      antifungal agents. Methods: Three antifungal agents, one synthetic - fluconazole,
      and two natural - oregano oil and virgin coconut oil were added into the tissue
      conditioner (Viscogel) in different concentrations. The antifungal property,
      tensile bond strength and viscoelasticity of Viscogel containing these antifungal
      agents were assessed after 24 hours, three days and seven days. Results: While,
      the highest antifungal activity was shown by Viscogel containing fluconazole, the
      maximum tensile bond strength was found to be of Viscogel alone (control).
      Although Viscogel alone and in combination of fluconazole showed deterioration in
      viscoelasticity, Viscogel in combination of natural agents showed no significant
      changes over the period of seven days. Conclusion: Incorporation of the natural
      agents in the tissue conditioner can be used as an effective alternative to
      systemic or topical synthetic antifungal agents.

PMID- 29071234
TI  - Effects of Herbal Compound (IMOD) on Behavior and Expression of Alzheimer's
      Disease Related Genes in Streptozotocin-Rat Model of Sporadic Alzheimer's
      Disease.
AB  - Purpose: Sporadic Alzheimer's disease (AD) accounts for over 95% of cases.
      Possible mechanisms of AD such as inflammation and oxidative stresses in the
      brain motivate researchers to follow many therapies which would be effective,
      especially in the early stages of the disease. IMOD, the herbal extract of R.
      Canina, T. Vulgare and U. Dioica plant species enriched with selenium, has anti
      inflammatory, immunoregulatory and protective effects against oxidative stress.
      Methods: In this study three AD-related genes, DAXX, NFkappabeta and VEGF, were
      chosen as candidate to investigate the neuroprotective effect of the extract by
      comparing their expression levels in the hippocampus of rat model of sporadic AD,
      using qPCR in the herbal-treated and control groups. The therapeutic effects on
      learning and memory levels were evaluated by Morris Water Maze (MWM) test.
      Results: Gene expression results were indicative of significant up-regulation of
      Vegf in rat's hippocampus after treatment with the herbal extract comparing to
      model group (P-value= 0.001). The MWM results showed significant changes in path
      length and time for finding the hidden platform in all groups during test and the
      same change in the treated comparing to the control group in memory level.
      Conclusion: It could be concluded that the herbal extract may have significant
      effect on gene expression but not on behavioral level.

PMID- 29071235
TI  - Effects of Thyroid Hormone on Urinary Concentrating Ability.
AB  - BACKGROUND: Hypothyroidism has been associated with impaired urinary
      concentrating ability. However, previous reports on thyroid hormone and urinary
      concentrating ability in humans only studied a limited number of patients with
      autoimmune thyroid disease or used healthy controls instead of paired analysis
      within the same patients. OBJECTIVE: To study the urinary concentrating ability
      in athyreotic patients with differentiated thyroid cancer on and off
      levothyroxine treatment as they are exposed to different thyroid states as part
      of their treatment in the absence of an autoimmune disease. DESIGN AND METHODS:
      We studied 9 patients (mean age of 42.7 years) during severe hypothyroid state
      (withdrawal of levothyroxine before radioactive iodine therapy) and TSH
      suppressed state (on levothyroxine therapy). At these two points, serum and urine
      samples were collected after 14 h of overnight fasting without any food or drink.
      RESULTS: Serum and urine osmolality were not significantly different between on
      and off levothyroxine treatment. Serum creatinine levels were significantly
      higher in patients off versus on levothyroxine treatment (87.0 vs. 71.0 umol/L,
      respectively; p = 0.044) and, correspondingly, the estimated glomerular
      filtration rate was significantly lower (89.6 vs. 93.1 mL/min, respectively; p =
      0.038). CONCLUSION: Short-term, severe hypothyroidism has no effect on urinary
      concentrating ability. Our study confirms the well-known effects of thyroid
      hormone on serum creatinine concentrations.

PMID- 29071236
TI  - Performance and Specificity of 6 Immunoassays for TSH Receptor Antibodies: A
      Multicenter Study.
AB  - BACKGROUND: The measurement of TSH receptor (TSHR) antibodies is warranted for
      diagnosis of Graves' disease (GD). OBJECTIVE: The performance, detection
      sensitivity, and specificity of 6 TSHR immunoassays were compared. METHODS: Two
      bioassays and 4 binding assays (Kronus, Immulite, Kryptor, Dynex) were compared
      in a dilution study performed in patients with autoimmune thyroid disease. Both
      bioassays were compared to 2 binding assays using stimulatory (M22) and blocking
      (K1-70) monoclonal antibody (MAb) mixtures. RESULTS: Thirty samples from
      stimulatory (TSAb)-positive/blocking (TBAb)-negative patients with GD were
      diluted serially and measured in all assays. Samples were positive until dilution
      1:2,187 in the TSAb bioassay, 1:81 in the Immulite (p < 0.002 vs. bioassay) and
      Kronus ELISA (p = 0.039) assays, and 1:27 in the Kryptor and Dynex ELISA (p <
      0.001 vs. bioassay). Ten samples from TBAb-positive/TSAb-negative patients with
      GD or Hashimoto's thyroiditis were positive in all binding assays. None of the
      binding assays differentiated between TSAb and TBAb. Mixtures of 100% K1-70 (200
      ng/mL), 80% K1-70 + 20% M22, 60% K1-70 + 40% M22, 40% K1-70 + 60% M22, 20% K1-70
      + 80% M22, and 100% M22 (20 ng/mL) tested positive in both Immulite (26.4, 20.2,
      15.2, 10.5, 6.3, 2.00 IU/L) and Kronus assays (27.1, 23.3, 19.3, 12.0, 5.7, 2.2
      IU/L). These MAb mixtures were tested in the TBAb bioassay and showed 82, 61, 24
      (negative), -26 (negative), -77 (negative), and -95% (negative) inhibition,
      respectively. CONCLUSIONS: The sample dilution study showed higher detection
      sensitivity for the TSAb bioassay, and the antibody mixture study demonstrated
      exclusive specificity of the bioassays over all automated and ELISA binding
      assays.

PMID- 29071237
TI  - The Effect of Daily versus Weekly Levothyroxine Replacement on Thyroid Function
      Test in Hypothyroid Patients at a Tertiary Care Centre in Haryana.
AB  - OBJECTIVE: We compare the effect of daily versus weekly levothyroxine (LT4)
      replacement on thyroid function test (TFT) in hypothyroid patients at a tertiary
      care centre in Haryana. MATERIALS AND METHODS: This was a randomised crossover
      study in which 100 hypothyroid patients on a stable LT4 dose were divided into 2
      groups of 50 each. In group I, patients were given daily therapy for 6 weeks and
      then shifted to weekly therapy for the next 6 weeks. In group II, patients were
      given LT4 once a week for 6 weeks and then switched to daily therapy for the next
      6 weeks. TFT, quality of life (QOL), and hyperthyroidism symptom scale (HSS)
      score of patients were compared in each group at 0, 6, and 12 weeks. RESULTS: TFT
      remained within the normal range, but TSH increased (group I, daily 2.8 +/- 1.4
      mIU/L, weekly 3.9 +/- 1.1 mIU/L, p = 0.001; group II, weekly 4.6 +/- 1.1 mIU/L,
      daily 2.7 +/- 1.2 mIU/L, p = <0.001) and T3/T4 decreased with weekly therapy as
      compared to daily therapy. No significant difference in HSS score was found
      between daily and weekly administration of LT4. With weekly therapy, QOL showed
      improvement in bodily pain, vitality, mental health, and social functioning.
      CONCLUSION: Once-weekly LT4 administration is a reasonable alternative for
      patients, especially for those who have issues with compliance.

PMID- 29071238
TI  - Prolonged Duration of Surgery Predicts Postoperative Hypoparathyroidism among
      Patients Undergoing Total Thyroidectomy in a Tertiary Referral Centre.
AB  - BACKGROUND: Postoperative hypoparathyroidism is a common complication following
      total thyroidectomy. The aim of this study was to investigate the incidence of
      both transient and permanent hypoparathyroidism in patients undergoing total
      thyroidectomy in a tertiary referral centre and, furthermore, to identify early
      predictive risk factors. METHODS: Based on a single-institution retrospective
      review, we identified 582 patients who underwent total thyroidectomy between
      January 2010 and March 2015. Information on age, gender, pathological diagnosis,
      duration of surgery, autotransplantation of parathyroid glands, neck dissection,
      and experience and position of the surgeon was retrieved from the medical
      records. Furthermore, serum levels of parathyroid hormone and calcium were
      registered pre- and postoperatively and after 3 and 12 months. RESULTS: The
      incidence of transient hypoparathyroidism during the first 24 h and 3 months
      after surgery was 47.8 and 17.8%, respectively. Furthermore, the incidence of
      permanent hypoparathyroidism 1 year after surgery was 10.7%. A prolonged duration
      of surgery was significantly associated with hypoparathyroidism. Moreover,
      autotransplantation of parathyroid glands was a significant predictor of
      transient hypoparathyroidism after 24 h and 3 months, but was not associated with
      permanent hypoparathyroidism. CONCLUSIONS: Transient and permanent
      hypoparathyroidism is common among patients undergoing total thyroidectomy in a
      tertiary referral centre. A duration of surgery >120 min constitutes an
      independent risk factor due to the risk of ischaemic damage. Regain of function
      of devascularized parathyroid glands must be expected to last at least 1 year
      postoperatively. Furthermore, the recovery of autotransplanted parathyroid glands
      should not be evaluated within 1-3 months after surgery.

PMID- 29071239
TI  - Does Graves' Orbitopathy Ever Disappear? Answers to an Old Question.
AB  - OBJECTIVES: There is a general belief that Graves' orbitopathy (GO) is a
      "chronic" disease, namely that patients' eyes do not return to how they were
      before GO appeared. Here, we investigate this issue from both the patient's and
      the physician's point of view. STUDY DESIGN: We studied the disappearance of GO,
      regardless of treatment, in all consecutive patients with a GO history of at
      least 10 years who came for a follow-up visit over a period of 5 years. Patients
      underwent an ophthalmological examination and were asked to answer a
      questionnaire on self-perception related to GO. RESULTS: We studied 99
      consecutive patients with a GO duration >=10 years. Between the first and the
      last observation, patients received several types of treatment for their thyroid
      disease and/or for GO. At the end of follow-up, GO was considered disappeared
      based on objective criteria in 8 patients (~8%) and based on subjective criteria
      in 24 patients (~24%). When we considered both subjective and objective criteria,
      only 2 patients (~2%) had all criteria fulfilled and could be considered as GO
      free. CONCLUSIONS: GO is a chronic disease in the vast majority of patients. Even
      after a very long time since its onset, complete disappearance is rare, although
      a minority of patients believe they do not have GO anymore and an even lower
      proportion do not have relevant GO signs. Our findings have obvious implications
      in patient management and counseling.

PMID- 29071240
TI  - Atypia of Undetermined Significance in Thyroid Fine Needle Aspirates: a 4-Year
      Audit of Thy3a Reporting.
AB  - OBJECTIVE: Thyroid nodules are common within the general population. Cytological
      analysis of fine needle aspirates (FNAs) of these lesions allows for
      identification of those that require further surgery. A numerical classification
      system is in place to streamline reporting. The 3a category is used for lesions
      that are neither benign nor malignant but show atypia of undetermined
      significance. We reviewed our use and clinical outcomes of Thy3a over a 4-year
      period. METHODS: All thyroid FNAs performed at this institute from January 2012
      to December 2015 were identified from our laboratory information system using
      SNOMED codes. Cytology was correlated with histology. RESULTS: Of the 1,259 FNAs
      reported at this institute, Thy3a constituted only 1.2% (n = 16) of all cases,
      with a malignancy rate of 7%. Five Thy3a cases had a repeat FNA that was reported
      as Thy2 (benign), 1 as Thy1c (cyst), 1 as Thy3f (follicular lesion), and 1 as
      Thy5 (malignant). Six cases without repeat FNA were follicular adenomas at
      resection. Two cases were lost to follow-up. Within all thyroid cytology
      categories in this 4-year period, we had a false-positive rate of 1.9% and a
      false-negative rate of 0.3%. CONCLUSIONS: The Thy3a subclassification has varied
      diagnostic criteria and lacks reproducibility. Despite the rare use of the Thy3a
      category at our centre, our diagnostic accuracy remained high. At this time,
      further Thy3a cohort studies are required to assess the real benefits of this
      category.

PMID- 29071241
TI  - Total Thyroidectomy for Thyroid Cancer Followed by Thyroid Storm due to
      Thyrotropin Receptor Antibody Stimulation of Metastatic Thyroid Tissue.
AB  - BACKGROUND: Graves disease (GD) is an autoimmune condition characterized by the
      presence of antibodies against the thyrotropin receptor (TRAB), which stimulate
      the thyroid gland to produce excess thyroid hormone. Theoretically, TRAB could
      stimulate highly differentiated thyroid cancer tissue and/or metastases to
      produce thyroid hormone. CASE: A 68-year-old male, with weight loss and
      palpitations, was diagnosed with thyrotoxicosis. A later MRI, due to persistent
      shoulder pain, revealed multiple bone metastases. A biopsy was diagnostic for
      follicular variant of papillary thyroid carcinoma, and total thyroidectomy was
      performed. One week after thyroidectomy the patient was admitted with severe
      hyperthyroidism. TRAB was >40 IU/mL (normal <0.7 IU/mL). High-dose antithyroid
      drug treatment was followed by high-dose radioactive iodine-131 (RAI) and local
      radiotherapy covering the right shoulder. Antithyroid drug treatment continued
      until after the fourth RAI dose. Hypothyroidism did not occur until following the
      fifth RAI treatment. SUMMARY AND CONCLUSIONS: We present a patient initially
      diagnosed with thyrotoxicosis and subsequently with metastatic follicular variant
      of papillary thyroid cancer. It is suggested that TRAB stimulated the highly
      differentiated extrathyroidal metastatic thyroid tissue to produce excessive
      amounts of thyroid hormone, delayed diagnosis, and potential aggravation of the
      course of thyroid cancer.

PMID- 29071242
TI  - Listeria monocytogenes biofilm production on food packaging materials submitted
      to physical treatment.

PMID- 29071243
TI  - Pulsed-field profile diversities of Salmonella Enteritidis, S. Infantis, and S.
      Corvallis in Japan.
AB  - The diversity of pulsed-field profiles (PFPs) within non-typhoidal Salmonella
      subtypes influences epidemiological analyses of Salmonella outbreaks. Therefore,
      determining the PFP diversity of each Salmonella serovar is important when
      evaluating current circulating strains. This study examined the PFP diversity of
      three important public health Salmonella enterica subspecies enterica serovars,
      S. Enteritidis (n=177), S. Infantis (n=205), and S. Corvallis (n=90), using
      pulsed-field gel electrophoresis. Isolates were collected from several sources,
      primarily from chicken-derived samples, in the Kyushu-Okinawa region of Japan
      between 1989 and 2005. S. Enteritidis isolates displayed 51 distinct PFPs (E
      PFPs), with 92 (52.0%) and 32 (18.1%) isolates displaying types E-PFP1 and E
      PFP10, respectively. The 205 S. Infantis isolates showed 54 distinct PFPs (I
      PFPs), with 87 (42.4%) and 36 (17.6%) isolates being I-PFP4 and I-PFP2,
      respectively. I-PFP18 was the dominant I-PFP of layer chicken isolates across a 5
      year period. Fourteen distinct S. Corvallis PFPs were detected. Simpson's index
      results for the genetic diversities of S. Enteritidis, S. Infantis, and S.
      Corvallis isolates were 0.70, 0.79, and 0.78, respectively. None of the E-PFPs or
      I-PFPs of layer chicken isolates overlapped with those of broiler chicken
      isolates, and the dominant clonal lines existed for >10 years. In conclusion,
      limited PFP diversities were detected amongst S. Enteritidis, S. Infantis, and S.
      Corvallis isolates of primarily chicken-derived origins in the Kyushu-Okinawa
      region of Japan. Therefore, it is important to take into account these
      limitations in PFP diversities in epidemiological analyses of Salmonella
      outbreaks.

PMID- 29071244
TI  - Assessment of relationship between rainfall and Escherichia coli in clams
      (Chamelea gallina) using the Bayes Factor.
AB  - Consumption of bivalve shellfish harvested from water contaminated with sewage
      pollution presents a risk of human infections and targeting control measures
      require a good understanding of environmental factors influencing the transport
      and the fate of faecal contaminants within the hydrological catchments. Although
      there has been extensive development of regression models, the point of this
      paper, focused on the relationship between rainfall events and concentrations of
      Escherichia coli monitored in clams, was the use of a Bayesian approach, by the
      Bayes Factor. The study was conducted on clams harvested from the south coast of
      Marche Region (Italy), a coastal area impacted by continuous treated effluents,
      intermittent rainfalldependent untreated sewage spillage - as a consequence of
      stormwater overflowing - and rivers with an ephemeral flow regime. The work
      compared the different interpretation criteria of Bayes Factor, confirmed that E.
      coli concentrations in clams from the studied area varied in correlation with
      rainfall events, and demonstrated the effectiveness of Bayes Factor in the
      assessment of shellfish quality in coastal marine waters. However, it suggested
      that further investigations would be warranted to determine which environmental
      factors provide the better basis for accurate and timely predictions. Furthermore
      the gathered data could be useful, to the local authorities of Marche Region, in
      the definition of flexible monitoring programmes, taking into account the
      atmospheric events that could affect the correct functioning of sewage managing
      systems and the flow of tributary rivers.

PMID- 29071245
TI  - Effect of a commercial steam-vacuuming treatment implemented after slaughtering
      for the decontamination of cattle carcasses.
AB  - To assess the antimicrobial effect of a commercial steam-vacuuming system newly
      implemented after slaughtering, 105 cattle carcasses were examined for total
      viable counts (TVC) at four different areas. Before steam vacuuming, mean TVC of
      the excision samples were comparable at the perineal area and brisket (3.0-3.1
      log CFU cm-2) or the hind leg and shoulder (2.6-2.7 log CFU cm-2). Steam
      vacuuming reduced mean TVC by 0.9, 0.7, 0.6, and 0.4 log CFU cm-2 at the perineal
      area, hind leg, shoulder, and brisket, respectively. With regard to the
      distribution of counts, steam vacuuming increased the proportion of TVC results
      <3.0 log CFU cm-2 from 74.8% (62.9-87.6% at carcass areas) to 86.7% (71.4-97.1%
      at carcass areas). Thus, steam vacuuming after slaughtering might be useful for
      the reduction of contamination in designated carcass areas, but the effect must
      not be overestimated and decontamination treatments always must be seen part of
      an integral food safety system.

PMID- 29071247
TI  - Contribution of street food on dietary acrylamide exposure by youth aged nineteen
      to thirty in Perugia, Italy.
AB  - Acrylamide dietary intakes from selected street foods in youth population are
      estimated. The intake evaluation was carried out by combining levels of
      acrylamide in food, analytically determined by high performance liquid
      chromatography, with individual consumption data recorded using a questionnaire
      applied to a group of 200 students aged 19 to 30. The mean value of acrylamide
      exposure was recorded to be 0.452 ug/kg bw/day, while the average intakes at 50th
      and 95th percentile were 0.350 ug/kg bw/day and 1.539 ug/kg bw/day, respectively.
      The street food categories that contributed the most to acrylamide intake are
      pizza and French fries. The margins of exposure, based on benchmark dose limits
      defined for neoplastic effects and peripheral neuropathy, are within the range of
      values that indicate a concern for public health as defined by European Authority
      for Food Safety (EFSA), confirming the needed effort to reduce acrylamide dietary
      exposure.

PMID- 29071246
TI  - Whole genome sequencing for typing and characterisation of Listeria monocytogenes
      isolated in a rabbit meat processing plant.
AB  - Listeria monocytogenes is a food-borne pathogen able to survive and grow in
      different environments including food processing plants where it can persist for
      month or years. In the present study the discriminatory power of Whole Genome
      Sequencing (WGS)-based analysis (cgMLST) was compared to that of molecular typing
      methods on 34 L. monocytogenes isolates collected over one year in the same
      rabbit meat processing plant and belonging to three genotypes (ST14, ST121,
      ST224). Each genotype included isolates indistinguishable by standard molecular
      typing methods. The virulence potential of all isolates was assessed by Multi
      Virulence-Locus Sequence Typing (MVLST) and the investigation of a representative
      database of virulence determinant genes. The whole genome of each isolate was
      sequenced on a MiSeq platform. The cgMLST, MVLST, and in silico identification of
      virulence genes were performed using publicly available tools. Draft genomes
      included a number of contigs ranging from 13 to 28 and N50 ranging from 456298 to
      580604. The coverage ranged from 41 to 187X. The cgMLST showed a significantly
      superior discriminatory power only in comparison to ribotyping, nevertheless it
      allows the detection of two singletons belonging to ST14 that were not observed
      by other molecular methods. All ST14 isolates belonged to VT107, which 7-loci
      concatenated sequence differs for only 4 nucleotides to VT1 (Epidemic clone III).
      Analysis of virulence genes showed the presence of a fulllength inlA version in
      all ST14 isolates and of a mutated version including a premature stop codon
      (PMSC) associated to attenuated virulence in all ST121 isolates.

PMID- 29071248
TI  - Evaluation of bovine beta casein polymorphism in two dairy farms located in
      northern Italy.
AB  - Bovine beta casein A1 is one of the most common variants in dairy cattle breeds;
      it is considered a risk factor in milk intolerance and in other important human
      diseases, because of the bioactive peptide beta casomorphin-7 (BCM7) produced by
      raw or processed A1-milk, but not by A2-milk, during digestion. The aim of this
      study was to perform a cheap and rapid method to investigate beta casein
      polymorphism in copious animals. The study included 2 dairy farms with a totally
      of 1230 cows. Beta casein genotypes were estimated evaluating Exon 7 region of
      bovine beta casein gene (CSN2) by sequences analysis. In the population included
      in the study 5 variants (A1, A2, B, F, I) and 13 genotypes (A1A1, A1A2, A1B, A1F,
      A1I, A2A2, A2B, A2F, A2I, BB, BF, BI, FI) were detected. The method showed high
      sensibility and specificity, resulted low-cost and few time consuming.

PMID- 29071249
TI  - Determination of plasmatic cortisol for evaluation of animal welfare during
      slaughter.
AB  - The plasmatic cortisol levels of 60 eight-month-old calves (Charolais breed) were
      measured as stress indicators resulting from two types of slaughter: traditional
      and religious rite. The plasmatic cortisol levels were evaluated during three
      different stages of their productive life: during growth, after transport and
      during slaughter. The thirty calves slaughtered after stunning showed plasmatic
      cortisol values of 4.85+/-3.2; 36.36+/-12.2 and 45.08+/-14.1 nmol/L, during
      growth, in the slaughterhouse stables and during exsanguination, respectively.
      Conversely, the average values found in the thirty calves subjected to ritual
      slaughter were 2.96+/-1.2; 31.65+/-25.4 and 68.70+/-30.6 nmol/L. The results of
      the study showed that animal welfare should be improved in both forms of
      slaughter.

PMID- 29071250
TI  - Defining Disease Modifying Therapy for Alzheimer's Disease.
AB  - BACKGROUND: Disease-modifying therapies (DMTs) are urgently needed to treat the
      growing number of individuals with Alzheimer's disease (AD) or at immanent risk
      for AD. A definition of DMT is required to facilitate the process of DMT drug
      development. PROCESS: This is a review of the state of the science with regard to
      definition and development of DMTs. RESULTS: A DMT is as an intervention that
      produces an enduring change in the clinical progression of AD by interfering in
      the underlying pathophysiological mechanisms of the disease process that lead to
      cell death. Demonstration of DMT efficacy is garnered through clinical trial
      designs and biomarkers. Evidence of disease modification in the drug development
      process is based on trial designs such as staggered start and delayed withdrawal
      showing an enduring effect on disease course or on combined clinical outcomes and
      correlated biomarker evidence of an effect on the underlying pathophysiological
      processes of the disease. Analytic approaches such as showing change in slope of
      cognitive decline, increasing drug-placebo difference over time, and delay of
      disease milestones are not conclusive by themselves but support the presence of a
      disease modifying effect. Neuroprotection is a related concept whose
      demonstration depends on substantiating disease modification. No single type of
      evidence in itself is sufficient to prove disease modification - consistency,
      robustness, and variety of sources of data will all contribute to convincing
      stakeholders that an agent is a DMT. CONCLUSION: DMT is defined by its enduring
      effect on processes leading to cell death. A variety of types of data can be used
      to support the hypothesis that disease modification has occurred.

PMID- 29071251
TI  - A study on the prevalence of risk factors for diabetes and hypertension among
      school children in Majmaah, Kingdom of Saudi Arabia.
AB  - BACKGROUND: The prevalence of risk factors for diabetes and hypertension in Saudi
      school children has achieved epidemic proportions because of enriched lifestyles.
      The aim of this study is to conduct a baseline study of such risk factors in a
      young population at the cusp of high-end technology and material comfort.
      MATERIALS AND METHODS: A cross-sectional study was done among school children
      using parental assisted self-questionnaires and anthropometric assessment of
      their vital statistics. This study, including planning, data collection and
      analysis, and the writing of the first draft, was conducted from March 2015 to
      October 2016 after ethical approval was obtained. Cluster sampling was done for
      the schools, and stratified randomized sampling was performed to choose a total
      of 794 male and female school children. SPSS software was used for data analysis.
      RESULTS: It was found that 11.6% of the children had a body mass index (BMI)
      above the normal range. The waist-to-height ratio was elevated in 16.8% of the
      children. Other risk factors of note were a high prevalence of sedentary habits
      (43%), daily consumption of carbonated sugary drinks (36.4%), and eating at fast
      food restaurants most days of the week (17%). CONCLUSIONS: This gradual buildup
      of risk factors for diabetes and hypertension at an early age is a morbid
      indicator of an epidemic whose outcome has been determined. Most of these
      modifiable risk factors are amenable to change through concentrated efforts to
      educate, train and inculcate healthy habits among children and their families. : 

PMID- 29071252
TI  - Factors related to reduction in the consumption of fast food: application of the
      theory-based approaches.
AB  - BACKGROUND: The Trans-Theoretical model (TTM) and Theory of Planned Behaviour
      (TPB) may be promising models for understanding and predicting reduction in the
      consumption of fast food. The aim of this study was to examine the applicability
      of the Trans-Theoretical model (TTM) and the additional predictive role of the
      subjective norms and perceived behavioural control in predicting reduction
      consumption of fast food in obese Iranian adolescent girls. MATERIALS AND
      METHODS: A cross sectional study design was conducted among twelve randomly
      selected schools in Sabzevar, Iran from 2015 to 2017. Four hundred eighty five
      randomly selected students consented to participate in the study. Hierarchical
      regression models used to predict the role of important variables that can
      influence the reduction in the consumption of fast food among students. using
      SPSS version 22. RESULTS: Variables Perceived behavioural control (r=0.58,
      P<0.001), Subjective norms (r=0.51, P<0.001), self-efficacy (r=0.49, P<0.001),
      decisional balance (pros) (r=0.29, P<0.001), decisional balance (cons) (r=0.25,
      P<0.001), stage of change (r=0.38, P<0.001), were significantly and positively
      correlated while experiential processes of change (r=0.08, P=0.135) and
      behavioural processes of change (r=0.09, P=0.145), were not significant.
      CONCLUSIONS: The study demonstrated that the TTM (except the experiential and
      behavioural processes of change) focusing on the perceived behavioural control
      and subjective norms are useful models for reduction in the consumption of fast
      food. : 

PMID- 29071253
TI  - Cancer screening information at community health fairs: What the participants do
      with information they receive.
AB  - BACKGROUND: To assess participants' reasons for seeking cancer screening
      information at community health fairs and what they do with the information they
      receive. DESIGN AND METHODS: Mixed quantitative and qualitative approach was
      used. Community health fairs are organized in underserved New York City
      neighbourhoods. From June 14, 2016 to August 26, 2016, cancer prevention tables
      providing information about various cancer screenings were established at 12
      local community health fairs in New York City. In-person and follow up telephone
      surveys assessing interest in the cancer prevention table, personal cancer
      screening adherence rates, information-sharing behaviours and demographic
      variables have been taken into account. Statistical analyses were performed using
      IBM SPSS 22.0: frequencies, descriptive, cross tabulations. All qualitative data
      was coded by theme so that it could be analysed through SPSS. For example, Were
      you interested in a specific cancer? may be coded as 2 for yes, breast cancer.
      RESULTS: One hundred and sixteen patrons participated in the initial survey. Of
      those, 88 (78%) agreed to give their contact information for the follow-up survey
      and 60 follow-up surveys were completed (68%). Of those who reported reading the
      material, 45% shared the information; 15% subsequently spoke to a provider about
      cancer screenings and 40% intended to speak to a provider. CONCLUSIONS:
      Participants disseminated information without prompting; suggesting the reach of
      these fairs extends beyond the people who visit our table. Future studies should
      look at whether patrons would share information at higher rates when they are
      explicitly encouraged to share the information. : 

PMID- 29071254
TI  - Breast cancer surgical treatment choices in Newfoundland and Labrador, Canada:
      Patient and surgeon perspectives.
AB  - BACKGROUND: Breast cancer remains the second-leading cause of cancer death among
      Canadian women. Treatment for breast cancer often includes surgery. Many women
      have a choice between mastectomy (MT; removal of the entire breast) or breast
      conserving surgery (BCS; removal of the tumour and some noncancerous breast
      tissue) followed by radiation. However, Newfoundland and Labrador consistently
      has a higher rate of mastectomies than the rest of Canada. In this project, we
      aim to better understand that trend. DESIGN AND METHODS: A multi-method design
      was chosen. Surgical treatment data kept by the province will be examined to
      describe the number and types of breast cancer surgeries over time. Second, we
      will hold focus groups with women around the province who have made surgical
      treatment choices to explore influences on their decisions. Finally, semi
      structured interviews with breast cancer surgeons and surgical residents will
      explore their opinions on surgical treatment choices. EXPECTED IMPACT FOR PUBLIC
      HEALTH: Cancer treatment choices are complex decisions, affected by clinical,
      demographic and social variables. Understanding why women from Newfoundland and
      Labrador have the highest rate of mastectomy in Canada is critical to ensure they
      are receiving appropriate screening and care. Greater understanding of the
      influences on women's surgical choices may encourage informed decisions amongst
      women and physicians and promote active communication about treatment, benefits
      relevant to all jurisdictions and health authorities. Further, if factors such as
      geographic proximity to treatment facilities are associated with treatment
      decisions, this information is important for public health screening and service
      planners. : 

PMID- 29071255
TI  - Spatial scale in environmental risk mapping: A Valley fever case study.
AB  - BACKGROUND: Valley fever is a fungal infection occurring in desert regions of the
      U.S. and Central and South America. Environmental risk mapping for this disease
      is hampered by challenges with detection, case reporting, and diagnostics as well
      as challenges common to spatial data handling. DESIGN AND METHODS: Using 12,349
      individual cases in Arizona from 2006 to 2009, we analyzed risk factors at both
      the individual and area levels. RESULTS: Risk factors including elderly
      population, income status, soil organic carbon, and density of residential area
      were found to be positively associated with residence of Valley fever cases. A
      negative association was observed for distance to desert and pasture/hay land
      cover. The association between incidence and two land cover variables (shrub and
      cultivated crop lands) varied depending on the spatial scale of the analysis.
      CONCLUSIONS: The consistence of age, income, population density, and proximity to
      natural areas supports that these are important predictors of Valley fever risk.
      However, the inconsistency of the land cover variables across scales highlights
      the importance of how scale is treated in risk mapping. : 

PMID- 29071256
TI  - Accuracy of the WHO's body mass index cut-off points to measure gender- and age
      specific obesity in middle-aged adults living in the city of Rio de Janeiro,
      Brazil.
AB  - INTRODUCTION: Obesity is defined by the World Health Organization (WHO) as a
      disease characterized by the excessive accumulation of body fat. Obesity is
      considered a public health problem, leading to serious social, psychological and
      physical problems. However, the appropriate cut-off point of body mass index
      (BMI) based on body fat percentage (BF%) for classifying an individual as obese
      in middle-aged adults living in Rio de Janeiro remains unclear. MATERIALS AND
      METHODS: This was a prospective cross-sectional study comprising of 856 adults
      (413 men and 443 women) living in Rio de Janeiro, Brazil ranging from 30-59 years
      of age. The data were collected over a two year period (2010-2011), and all
      participants were underwent anthropometric evaluation. The gold standard was the
      percentage of body fat estimated by bioelectrical impedance analysis. The optimal
      sensitivity and specificity were attained by adjusting BMI cut-off values to
      predict obesity based on the WHO criteria: BF% >25% in men and >35% in women,
      according to the receiver operating characteristic curve (ROC) analysis adjusted
      for age and for the whole group. RESULTS: The BMI cut-offs for predicting BF%
      were 29.9 kg/m2 in men and 24.9 kg/m2 in women. CONCLUSIONS: The BMI that
      corresponded to a BF% previously defining obesity was similar to that of other
      Western populations for men but not for women. Furthermore, gender and age
      specific cut-off values are recommended in this population. : 

PMID- 29071257
TI  - Validation of a scale to measure parental psychological empowerment in the
      vaccination decision.
AB  - BACKGROUND AND AIMS: Parents' empowerment is advocated to promote and preserve an
      informed and autonomous decision regarding their children' immunization. The
      scope of this study is to develop and evaluate the psychometric properties of an
      instrument to measure parents' psychological empowerment in their children's
      vaccination decision and propose a context-specific definition of this construct.
      MATERIALS AND METHODS: Grounding in previous qualitative data, we generated an
      initial pool of items which was later content and face validated by a panel of
      experts. A pretest allowed us to reduce the initial pool to 9 items. Convergent
      and discriminant validity measures included the General Self-Efficacy Scale, a
      Psychological Empowerment Scale, and the Control Preference Scale. Vaccination
      related outcomes such as attitude and intention were also included. RESULTS:
      Principal Component Analysis revealed a 2-factor structure, with each factor
      composed of 2 items. The first factor concerns the perceived influence of one's
      personal and family experience with vaccination, while the second factor
      represents the desire not to ask other parents about their experience with
      vaccination and their lack of interest in other parents' vaccination opinion.
      CONCLUSIONS: In light of its association with positive immunization-related
      outcomes, public health efforts should be directed to reinforce parents'
      empowerment. : 

PMID- 29071258
TI  - Older adults rate their mental health better than their general health.
AB  - BACKGROUND: Self-rated health (SRH) shows strong associations with measures of
      health and well-being. Increasingly, studies have used self-rated mental health
      (SRMH) as a predictor of various outcomes, independently or together with SRH.
      Research has not firmly established if and how these two constructs differ. We
      sought to characterize the relationship between SRH and SRMH, and to determine
      how this relationship differed across subgroups defined by sociodemographic and
      health-related characteristics. DESIGN AND METHODS: We analyzed data from the
      2012 CAHPS Medicare Advantage Survey. SRH and SRMH ratings were crosstabulated to
      determine the distribution of responses across response categories. The expected
      joint probability distribution was computed and compared to the observed
      distribution. A constructed variable indicated whether SRMH was better, the same,
      or worse than SRH. We analyzed the distribution of this variable across various
      subgroups defined by sociodemographic and health-related factors. RESULTS: A
      total of 114,905 Medicare Advantage beneficiaries responded to both the SRH and
      SRMH questions. Both in general and within all subgroups, SRMH was usually rated
      as better than SRH, and rarely as worse. CONCLUSIONS: Within a large group of
      Medicare recipients, the overwhelming trend was for recipients to rate their
      mental health as at least as good as their overall health, regardless of any
      sociodemographic and health-related factors. This finding of a shifted
      distribution encourages caution in the analytic use of selfrated mental health,
      particularly the use of both SRH and SRMH for adjustment. Additional research is
      needed to help clarify the complex relationship between these variables. : 

PMID- 29071259
TI  - Scaffold Proteins in Gastrointestinal Tumors as a Shortcut to Oncoprotein
      Activation.
AB  - BACKGROUND: The development of cancer involves uncontrolled cell proliferation,
      and multiple signaling pathways that regulate cell proliferation have been found
      to be dysregulated in cancers. Extracellular signal-regulated protein kinase
      (ERK) is one of three major subtypes in the mitogen-activated protein kinase
      (MAPK) families. The MAPK/ERK pathway (RAS/RAF1/MEK/ERK) plays an important part
      in promoting cell proliferation in response to growth factors, thereby serving as
      a driving signal in gastrointestinal (GI) tumors. In contrast, the p53 tumor
      suppressor functions as a "guardian of the genome" and stops cell proliferation
      when oncogenic signaling is activated. SUMMARY: Both pathways constrain each
      other in healthy GI epithelium, facilitating controlled proliferation that is
      essential for tissue repair and regeneration. However, in GI tumors, the MAPK/ERK
      and p53 pathways are commonly dysregulated, in part due to abnormal
      posttranslational modifications. Hyperphosphorylation of the ERK protein causes
      sustained activation of cell proliferation, whereas hypoacetylation of the p53
      protein impairs its transcriptional function and blocks cell apoptosis. Multiple
      scaffold proteins have been found to regulate the posttranslational modifications
      of ERK and p53 proteins in GI tumors. KEY MESSAGE: Abnormal expression of
      scaffold proteins may contribute to the dysregulation of the MAPK and p53
      signaling pathways and thereby contribute to the development of GI tumors.
      PRACTICAL IMPLICATIONS: Scaffold proteins are potential biomarkers and
      therapeutic targets in GI tumors.

PMID- 29071261
TI  - Diffuse-Type Hepatoma: A Grave Prognostic Marker.
AB  - BACKGROUND: Data on diffuse-type hepatocellular carcinoma (HCC) are rare. HCC in
      Sri Lanka is rising, and the majority is related to nonalcoholic fatty liver
      disease. This study was planned to compare nodular- and diffuse-type HCC in this
      cohort. METHODS: CT scans of 227 patients with HCC negative for infective
      hepatitis were analyzed and grouped as nodular and diffuse from July 2011 to July
      2014. Diffuse-type cancer was defined as a tumor without convex/distinct margin,
      diffusely infiltrating the hepatic parenchyma. There were 45 (20%) cases. The
      baseline liver functions, etiology, treatment, and the outcome were compared with
      nodular-type cancers. Stage III diffuse cancers were matched with 2 stage III
      nodular cancers looking at the T stage and background liver. RESULTS: There was
      no difference in the age (63 vs. 62 years, p = 0.937) and gender. Diffuse cancers
      had a low BMI (24 vs. 22, p = 0.009), a higher alpha fetoprotein (AFP) level (p <
      0.001), a higher incidence of major vascular invasion (14 vs. 80%, p < 0.001),
      and a history of significant alcohol consumption (39 vs. 67%, p = 0.001). The
      baseline liver functions were similar in diffuse and nodular cancers. A large
      proportion (27 vs.77%, p < 0.001) of diffuse cancers were not candidates for
      active treatment. Overall survival was poor in the diffuse type (4.7 vs. 25
      months, p < 0.001). Diffuse-type stage III cancers had a poor survival compared
      to matched nodular cancers (2.5 vs. 15.8 months, p = 0.001). CONCLUSION: HCC
      without a background of infective hepatitis were common in our cohort. These
      tumors are associated with high AFP levels, major vascular invasion, and a poor
      prognosis.

PMID- 29071260
TI  - Effect of Adjuvant Chemotherapy on Elderly Colorectal Cancer Patients: Lack of
      Evidence.
AB  - BACKGROUND: Adjuvant chemotherapy has become the standard form of treatment for
      all patients with stage III colorectal cancer and is also recommended for
      patients with stage II disease and defined risk factors. However, clinical
      studies that evaluate the effect of adjuvant treatment regimens have a selection
      bias in favor of younger patients, so that even retrospective subgroup analyses
      cannot define the best therapeutic procedure in elderly patients with
      comorbidities. SUMMARY: As long as the role of adjuvant chemotherapy in elderly
      colorectal cancer patients is not investigated in comprehensive trials, no clear
      recommendations are possible. KEY MESSAGE: An exploratory review of the relevant
      literature revealed that a formal meta-analysis concerning adjuvant chemotherapy
      in elderly patients with colorectal cancer is not feasible due to varying
      definitions of elderly patients, inclusion and exclusion criteria, and a plethora
      of chemotherapeutic regimens. PRACTICAL IMPLICATIONS: Given the high incidence of
      colorectal cancer and the median age of 68 years for patients at the time of
      diagnosis, health economic considerations should promote randomized controlled
      trials regarding the role of adjuvant chemotherapy in the elderly.

PMID- 29071262
TI  - Left Gastric Artery Reconstruction after Distal Pancreatectomy with Celiac Axis
      En-Bloc Resection: How We Do It.
AB  - BACKGROUND/AIMS: Ischemic gastropathy remains as a persistent problem after left
      gastric artery (LGA) resection in distal pancreatectomy with celiac axis en-bloc
      resection (DP-CAR). The middle colic artery (MCA) was found to be a useful vessel
      for compromised collateral flow. However, intraoperative gross evaluation of
      gastric ischemia is technically difficult even after artery reconstruction.
      METHODS: We performed LGA reconstruction by MCA-LGA bypass after LGA-resecting DP
      CAR assisted by intraoperative indocyanine green fluorescence imaging (ICG) blood
      flow evaluation in a clinical trial (UMIN000020414). The LGA was reconstructed
      with the MCA microscopically by plastic surgeons with an everting interrupted
      suture in end-to-end anastomosis. RESULTS: We could evaluate ICG blood flow not
      only in the reconstructed artery, but also simultaneously in the gastric wall
      through a monitor connected to a detector. We could also assess the congestive
      status of the gastric wall by ICG disappearance from the gastric wall.
      CONCLUSION: We present LGA reconstruction by MCA-LGA bypass after LGA-resecting
      DP-CAR. We conducted a perioperative assessment of ischemic gastropathy to
      confirm the feasibility and safety of this procedure.

PMID- 29071263
TI  - Mortality and Survival after Surgical Treatment of Colorectal Cancer in Patients
      Aged over 80 Years.
AB  - OBJECTIVE: The purpose of this study was to identify the clinical factors and
      tumor characteristics that predict the outcome of colorectal cancer patients aged
      >80 years. MATERIALS AND METHODS: The data of 186 patients aged >80 years with
      colorectal cancer were collected from a computer database, and the variables were
      analyzed by both uni- and multivariate analyses. RESULTS: The 30-day mortality
      was 4% and the 90-day mortality 10%. The 1-year survival was 76%, and 27 (61%) of
      the 44 deaths were unrelated to cancer. The overall 5-year survival was 36%, the
      median survival 38 months, and the cancer-specific survival 40%. The recurrence
      rate after radical surgery was 22% and it was not affected by age. Kaplan-Meier
      estimates indicated that age, number of underlying diseases, radical operation,
      Union for International Cancer Control stage of the tumor, tumor size, number of
      lymph nodes involved, venous invasion, and recurrent disease were significant
      predictors of survival, but in the Cox regression model, only radical operation
      and venous invasion were independent prognostic factors for survival.
      CONCLUSIONS: After good surgical selection, low early mortality and acceptable
      long-term survival can be achieved even in the oldest old patients with
      colorectal cancer. However, low early mortality seems to underestimate the
      effects of surgery during the first postoperative year.

PMID- 29071265
TI  - Freezing Fort Knox: Mesenteric Carcinoid Cryoablation.
AB  - BACKGROUND: Neuroendocrine malignancy is indolent, yet relentless in its
      propensity to metastasize to the liver, where it may cause bizarre paraneoplastic
      syndromes. The pathophysiologic mechanism behind this predilection for hepatic
      metastasis is twofold: the portal venous system drains the most likely primary
      sites for neuroendocrine tumors, and the relatively immunosuppressed environment
      within the hepatic parenchyma is permissive for tumor growth. The standard of
      care for patients with metastatic neuroendocrine tumor is surgical resection of
      at least 90% of the tumor burden. METHODS: This report describes CT-guided
      percutaneous cryoablation of an inoperable mesenteric carcinoid tumor that had
      previously demonstrated hepatic metastases utilizing hydrodissection to safely
      and effectively prevent further metastasis while priming the immune system to
      eradicate this malignancy systemically. RESULTS: CT-guided percutaneous
      cryoablation is minimally invasive, has intrinsic analgesic properties, and may
      contribute to sensitization of the immune system against tumor antigens.
      CONCLUSION: Percutaneous cryoablation with hydrodissection can be used to target
      intraabdominal malignancy in poor surgical candidates. This procedure is safe,
      effective, and minimally invasive.

PMID- 29071264
TI  - Oncological Outcomes following Rectal Cancer Surgery with High or Low Ligation of
      the Inferior Mesenteric Artery.
AB  - BACKGROUND: The level of inferior mesenteric artery (IMA) ligation for anterior
      resection of rectal cancer has several considerations concerning oncological
      outcomes. The primary endpoint of this randomized controlled trial (RCT) was to
      assess bowel function between high and low ligation. This study was intended to
      clarify oncological outcome as the secondary endpoint. OBJECTIVE: The aim of this
      study was to assess in a prospective RCT whether the ligation level of the IMA in
      rectal cancer influences oncological outcomes. METHODS: Between February 2008 and
      December 2011, 100 patients who underwent anterior resection for rectal cancer
      were randomized to perform either high or low ligation of the IMA. Oncological
      outcomes was the secondary endpoint of this RCT, whereas assessing bowel function
      was the primary endpoint. This RCT was registered at clinicaltrials.gov
      (NCT00701012). RESULTS: There were no differences between the groups in terms of
      clinical data except for tumor stage. There were more advanced-stage patients in
      the high ligation group (p = 0.046). There were no lymph node (LN) metastases in
      the root of the IMA in the high ligation group. The average number of harvested
      LNs for the high and low ligation groups was 16.7 and 14.9, respectively. There
      was no difference in disease-free survival (DFS), site of first recurrence, and
      overall survival (OS). When patients were in stage III, there was also no
      difference in DFS and OS. CONCLUSIONS: The ligation level of the IMA in rectal
      cancer may not influence oncological outcomes. However, further large-scale RCTs
      are needed to conclude this issue.

PMID- 29071266
TI  - Retinal Reactive Astrocytic Tumor (Focal Nodular Gliosis): The Entity Also Known
      as Vasoproliferative Tumor.

PMID- 29071267
TI  - Uveal Melanoma Cell Seeding after Transretinal Tumor Biopsy?
AB  - BACKGROUND/AIMS: To report a case and the histopathology of uveal melanoma cell
      seeding following transretinal tumor biopsy for a suspected uveal lesion.
      METHODS: Interventional case report. RESULTS: A 66-year-old male presented with a
      pigmented perilimbal episcleral lesion overlying an intraocular mass at the pars
      plana, 3.5 years after transretinal biopsy and ruthenium plaque brachytherapy for
      a choroidal melanoma at the posterior pole. The patient underwent enucleation of
      the eye. Histopathology confirmed a recurrence of uveal melanoma with intra- and
      extrascleral tumor portions. Serial sections revealed the posterior border of
      this newfound pars plana melanoma separated from the radiation scar by a viable
      and tumor-free choroidal area, thus failing to establish a continuity between
      secondary and primary tumor. CONCLUSION: Transretinal tumor biopsy is of high
      diagnostic and prognostic value in the management of uveal lesions, but also
      bears the potential risk for tumor cell seeding.

PMID- 29071268
TI  - Development of Ocular Rosacea following Combined Ipilimumab and Nivolumab
      Treatment for Metastatic Malignant Skin Melanoma.
AB  - PURPOSE: To report a case of severe ocular rosacea following ipilimumab plus
      nivolumab treatment in a patient with metastatic malignant skin melanoma.
      METHODS: Case report and review of the literature. RESULTS: A 68-year-old male
      with newly diagnosed metastatic malignant cutaneous melanoma was treated with
      first-line ipilimumab plus nivolumab, which resulted in a partial response. Four
      months after initiation of treatment, the patient developed red eyelids and
      conjunctivae, with painful gritty eyes, limiting his capacity to read. Following
      a diagnosis of severe ocular rosacea and dry eyes, treatment including
      corticosteroids, antimicrobial agents, and eyelid hygiene was started, and within
      3 months, the ocular complaints resolved. CONCLUSION: Treatment with checkpoint
      inhibitor immunotherapy for metastatic melanoma may trigger several ocular immune
      related adverse events. This case describes severe ocular rosacea as an adverse
      event following ipilimumab plus nivolumab treatment.

PMID- 29071270
TI  - Ciliary Body Mesectodermal Leiomyoma Diagnosed by Fine Needle Aspiration Biopsy.
AB  - AIMS: To describe the clinical, imaging, cytopathological, and
      immunohistochemical features of mesectodermal leiomyoma of the ciliary body
      diagnosed by fine needle aspiration biopsy in a patient who denied any major
      intervention without prior pathological verification. METHODS: The clinical,
      imaging, and cytopathological records of the patient were retrospectively
      reviewed. A fine needle aspiration biopsy with a 25-G needle was performed after
      tailoring a scleral flap. RESULTS: Examination of the cell blocks prepared from
      the aspirate demonstrated cells with granular cytoplasms and large nuclei.
      Immunohistochemical studies showed positive smooth muscle actin, desmin, h
      caldesmon, CD56, and neuron-specific enolase stainings, suggesting both
      neurogenic and myogenic differentiation. Reactions for HMB-45, S-100, panCK,
      epithelial membrane antigen, glial fibrillary acidic protein, and CD68 were
      negative. Because the tumor continued to enlarge, fractionated stereotactic
      radiotherapy at the dose of 3,000 cGy was delivered, which reduced the size of
      the mass by 40% in 5 years. CONCLUSIONS: This case demonstrated that the
      diagnosis of mesectodermal leiomyoma of the ciliary body can be established with
      fine needle aspiration biopsy and that stereotactic radiotherapy can be
      successfully used to induce tumor regression.

PMID- 29071269
TI  - Iodine-125 Brachytherapy for Uveal Melanoma: A Systematic Review of Radiation
      Dose.
AB  - AIM: To investigate whether lower radiation doses may yield similar outcome
      measures to those from the COMS trial. METHODS: A literature review of English
      language articles was performed using the PubMed database of the U.S. National
      Library of Medicine and the Cochrane Central Register of Controlled Trials using
      the following keywords: uveal melanoma, choroidal melanoma, primary uveal
      malignant melanoma, iodine-125 brachytherapy, local recurrence, local treatment
      failure, and local tumor control. The relationships between study local
      recurrence rate and median dosage were tested by linear regression, with each
      study weighted by the number of patients included. RESULTS: Fifteen retrospective
      and prospective studies were selected for systematic review (2,662 patients).
      Ranges of reported mean or median radiation dose to tumor apex were 62.5-104.0
      Gy. Local recurrence rates ranged from 0 to 24%. A 1.0-Gy increase in the average
      study dose was associated with a 0.14% decrease in local recurrence rate, which
      was not statistically significant (p value 0.336). CONCLUSION: The gold standard
      empirically derived 85.0-Gy radiation dose for the treatment of uveal melanoma
      could be tested in a randomized study.

PMID- 29071271
TI  - Monte Carlo Estimation of Absorbed Dose Distributions Obtained from Heterogeneous
      106Ru Eye Plaques.
AB  - BACKGROUND: The distribution of the emitter substance in 106Ru eye plaques is
      usually assumed to be homogeneous for treatment planning purposes. However, this
      distribution is never homogeneous, and it widely differs from plaque to plaque
      due to manufacturing factors. METHODS: By Monte Carlo simulation of radiation
      transport, we study the absorbed dose distribution obtained from the specific
      CCA1364 and CCB1256 106Ru plaques, whose actual emitter distributions were
      measured. The idealized, homogeneous CCA and CCB plaques are also simulated.
      RESULTS: The largest discrepancy in depth dose distribution observed between the
      heterogeneous and the homogeneous plaques was 7.9 and 23.7% for the CCA and CCB
      plaques, respectively. In terms of isodose lines, the line referring to 100% of
      the reference dose penetrates 0.2 and 1.8 mm deeper in the case of heterogeneous
      CCA and CCB plaques, respectively, with respect to the homogeneous counterpart.
      CONCLUSIONS: The observed differences in absorbed dose distributions obtained
      from heterogeneous and homogeneous plaques are clinically irrelevant if the
      plaques are used with a lateral safety margin of at least 2 mm. However, these
      differences may be relevant if the plaques are used in eccentric positioning.

PMID- 29071272
TI  - Conjunctival Blue Naevus in an Anophthalmic Socket.
AB  - PURPOSE OF THE STUDY: To describe an unusual brown pigmented lesion of the
      conjunctiva in an anophthalmic socket in a 16-year-old male. PROCEDURES: A 16
      year-old male patient presented with socket irritation whilst wearing an
      artificial eye due to meibomian gland dysfunction. An area of flat,
      subepithelial, dark brown pigmentation with irregular and indistinct borders on
      the bulbar conjunctiva of the anophthalmic socket was seen. The patient believed
      it had been present for at least 2 years. His past ocular history was of
      childhood trauma to the right eye at the age of 9 years, and he underwent primary
      enucleation and hydroxyapatite orbital implant insertion at that time.
      Unfortunately, the implant extruded and was removed a year later. RESULTS: An
      incisional biopsy of the pigmented lesion showed a conjunctival, subepithelial
      bland spindle cell melanocytic lesion, with uniform-sized and -shaped
      melanosomes. Immunohistochemistry showed the cells to express Melan A and HMB45
      and they were negative for CD68 and pan-cytokeratins. The features were of a
      common blue naevus. CONCLUSION: This is the first documentation of a post
      enucleation conjunctival naevus in an anophthalmic socket. We propose a
      pathogenesis and suggest surveillance as there is a risk of transformation to
      melanoma.

PMID- 29071273
TI  - Chronic Lymphocytic Leukaemia/ Small-Cell Lymphocytic Lymphoma of the Lacrimal
      Sac: A Case Series.
AB  - BACKGROUND: Lymphomas of the lacrimal sac are rare, accounting for less than 10%
      of lacrimal sac malignant tumours. They may present with symptoms typical of
      secondary acquired nasolacrimal duct obstruction and are thus often misdiagnosed.
      METHODS: Case series and literature review. RESULTS: Herein we describe 3 cases
      of chronic lymphocytic leukaemia (CLL)/small-cell lymphocytic lymphoma (SLL) of
      the lacrimal sac with immunohistochemical and in 1 case molecular confirmation.
      CONCLUSION: Lymphomas of the lacrimal sac should be suspected in patients with
      known CLL presenting with epiphora and dacryocystitis. During
      dacryocystorhinostomy, an incisional biopsy of the lacrimal sac is essential for
      confirming CLL/SLL involvement and may guide treatment.

PMID- 29071274
TI  - Bilateral Central Retinal Artery Occlusion Associated with Bilateral
      Lymphoproliferative Infiltrative Optic Neuropathy.
AB  - BACKGROUND: Leukemic infiltration of the optic nerve is relatively rare. While
      previously described in acute leukemia, the infiltration in our case represents
      central nervous system (CNS) metastasis of Burkitt-type lymphoma that developed
      as a complication of solid-organ transplantation, resulting in a bilateral
      infiltrative optic neuropathy with sequential, bilateral central retinal artery
      occlusion (CRAO) and devastating vision loss. METHODS: The medical record, serial
      ophthalmic examination findings, clinical course, and imaging including magnetic
      resonance imaging (MRI), fundus photographs, and fluorescein angiography of a
      single patient were retrospectively reviewed. RESULTS: MRI demonstrated
      multifocal cortical and leptomeningeal CNS involvement, including the left optic
      nerve. Serial fundus examination/photography and fluorescein angiography showed
      that despite urgent whole-brain irradiation and systemic chemotherapy, CNS
      disease progressed to bilateral optic nerve infiltration and CRAO with no light
      perception vision in both eyes. CONCLUSION: CRAO can occur as a devastating and
      irreversible complication of lymphoproliferative optic nerve infiltration.

PMID- 29071276
TI  - Small Choroidal Melanoma Revealed by a Large Extrascleral Extension.
AB  - AIMS: Orbital extraocular extension of choroidal melanoma is very rare with small
      melanomas. We report the case of a patient whose small choroidal melanoma was
      initially overlooked and was revealed by a large extrascleral extension. METHODS:
      A 48-year-old Caucasian woman presented with sudden total visual loss in the
      right eye. Multicolor imaging of the fundus showed right optic disc edema and an
      orange and green lesion near the optic disc. The diagnosis of unilateral optic
      neuritis was made. Magnetic resonance imaging showed an extraocular mass adjacent
      to the optic nerve; on ultrasound, this mass was acoustically hollow and a small
      intraocular component was visible. RESULTS: Choroidal melanoma with a large
      extrascleral extension was diagnosed (T4eN0M0, stage IIIC according to the AJCC
      7th TNM classification, 2010). The size of the extraocular nodule was 13 * 5 mm.
      Treatment consisted of enucleation followed by adjuvant external beam orbital
      radiotherapy. Tumor analysis showed a mixed cell type melanoma with monosomy 3.
      The patient developed liver metastasis 10 months after local treatment.
      CONCLUSION: Extraocular extension of choroidal melanoma can occur with small
      lesions. Prognosis is generally poor according to AJCC TNM. This case is a
      reminder that fundus examination may reveal the nature of the mass in some
      patients with orbital tumors.

PMID- 29071275
TI  - Reactive Retinal Astrocytic Tumor (Focal Nodular Gliosis): Report of the Clinical
      Spectrum of 3 Cases.
AB  - PURPOSE: To report 3 cases providing insight into clinical progression of
      reactive retinal astrocytic tumor. METHODS: The clinical, imaging, and when
      available, the cytologic features of 3 cases of reactive retinal astrocytic tumor
      (focal nodular gliosis) were reviewed. RESULTS: A 6-year-old female, a 49-year
      old man, and a 39-year-old man each developed a white retinal mass associated
      with laser photocoagulation, lattice degeneration, and treatment of a presumed
      vascular tumor, respectively. All tumors were white, circumscribed retinal masses
      that tended to be associated with exudation and either initially or eventually
      minimal vascularity. CONCLUSION: Reactive retinal astrocytic tumor can be
      observed in response to a degenerative, inflammatory, or ischemic retinal insult.
      Such tumors may progress after therapeutic intervention.

PMID- 29071277
TI  - EBUS-TBNA in PET-positive lymphadenopathies in treated cancer patients.
AB  - Mediastinal lymph node enlargement is common in the follow-up of patients with
      previously treated malignancies. The aim of this study is to assess the role of
      endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) for cyto
      histological evaluation of positron emission tomography with 18fluorodeoxyglucose
      (PET) positive mediastinal and hilar lymph nodes developed in patients with
      previous malignancies. All EBUS-TBNA cases performed from January 2012 to May
      2016 were retrospective reviewed. Results of EBUS-TBNA in patients with
      mediastinal and/or hilar lymphadenopathies were analysed. Non-malignant
      cytopathologies were confirmed with surgical procedures or clinical and
      radiological follow-up. Among 1780 patients, 176 were included in the analysis.
      103 of these (58.5%) had a diagnosis of tumour recurrence whereas 73 (41.5%) had
      a different diagnosis: 63 (35.8%) had a non-neoplastic diagnosis and 8 patients
      (4.6%) had a different cell type malignancy. Samples were false-negative in 5
      (2.8%) out of 176 patients. The overall sensitivity, specificity, negative
      predicted value and diagnostic accuracy were 95.7% (95% CI 90.2-98.6%), 100% (95%
      CI 94.0-100%), 92.3% (95% CI 83.2-96.7%) and 97.2% (95% CI 93.5-98.8%),
      respectively. EBUS-TBNA demonstrated a pathological diagnosis different from the
      previous tumour in a large percentage of patients, confirming its strategic role
      in the management of patients with previously treated malignancies.

PMID- 29071278
TI  - Association of glutathione S-transferase M1 and T1 polymorphisms and temperament.
AB  - Mizaj (Temperament) is one of the basic concepts of Iranian Traditional Medicine
      (ITM), which has great importance in diagnosis and treatment of diseases, as well
      as maintaining the ideal healthy state of an individual. However, very little is
      known about the biological mechanisms of mizaj dependence treatment in practical
      ITM. This study was aimed to evaluate any association between the mizaj and
      glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms in healthy
      people. The samples included 247 healthy males from Fars province, southern Iran.
      The mizaj was determined using a self-reported mizaj identification scale.
      Subjects with equilibrium or any of four simple mizajes (warm, cold, moist, and
      dry) were included in the study. The GSTM1 and GSTT1 genotypes were determined
      using a polymerase chain reaction (PCR)-based method. No any differences in the
      frequency of GSTM1/T1 polymorphism between equilibrium and each of other mizaj
      groups were found. However, when equilibrium, moist, and dry groups were pooled
      and as a "medium warmness" group were compared to the warm group, the frequency
      of GSTT1-null in the warm group was significantly higher compare to that in the
      medium warmness group. Also, the combination genotypes of GSTM1 and GSTT1 was
      associated with the warmness; that is, individuals with combination of GSTM1
      positive and GSTT1 null were more susceptible to have a warm temperament. This
      study indicated that the mizaj could be affected by GSTM1/T1 genes, although
      further research with larger samples is needed to reach full conclusions.

PMID- 29071280
TI  - Assessment of vocation of rifabutin and rifapentine in replace of rifampcin in
      drug resistance leprosy patients: a molecular simulation study.
AB  - The emergence of drug resistance in leprosy is a major hurdle in leprosy
      elimination programme. Although the problem of drug resistance is presently not
      acute, it is important that we collect data more systematically and monitor the
      trend carefully so that effective measures to combat this problem can be
      developed. The present study aimed at the explication of cross resistance of
      rifabutin and rifapentine to rifampicin which would be helpful to programme
      managers for implementing rifabutin or rifapentine in replace of rifampicin. In
      this study we built 3D model of the M. leprae rpoB using Swiss Model and the
      modelled structure was docked with rifampicin, rifabutin and rifapentine. We
      established that these 3 antibiotics interact with the same binding region in the
      modelled rpoB of M. leprae. Thus we conclude that vocation of rifabutin and
      rifapentine could not be suitable in replace of rifampicin to combat with drug
      resistance leprosy.

PMID- 29071281
TI  - Evaluation of VNTR polymorphisms of dopamine transporter gene and the risk of
      bipolar disorder in Zahedan, southeast Iran.
AB  - The exact role of dopamine transporter gene (DAT1) in the pathogenesis of bipolar
      disorder type 1 (BD) is not understood. In the present study, we aimed to
      evaluate the possible association between 30, 40 and 63 bp variable number tandem
      repeat (VNTR) polymorphisms of DAT1 gene and the risk of type 1 (BD) in a sample
      of Iranian population. This case-control study was performed on 152 BD patients
      and 153 psychiatrically healthy subjects. Genotyping of the variant was done by
      polymerase chain reaction method. Totally, the findings did not support an
      association between DAT1 VNTR polymorphisms and the risk of BD in a sample of
      southeast Iranian population.

PMID- 29071279
TI  - Immunogenic evaluation of chimeric recombinant protein against ETEC, EHEC and
      Shigella.
AB  - Diarrheal diseases still remain health problem worldwide and out of many bacteria
      responsible for, Shigella and pathogenic Escherichia cause the most diarrheas in
      the world. Shigellacause bacterial dysenteries and shigellosis through invasion
      where the most effective proteins for pathogenesis is Ipac. Critical virulence
      protein for ETEC infection is CFA/I with two subunits called cfab and cfae. .
      Attachment of EHEC is the main step of infection and the protein Intimin plays
      the key role in this function. Protection against the vast majority of
      responsible pathogens of diarrheas requires development of the combination
      vaccine against Shigella, ETEC and EHEC. In the present study, a
      multisubunitprotein (CII) containing immunologically significant parts of CfaB,
      IpaC and Intimin was designed. The chimeric gene (CII) was codon optimized and
      analyzed with different bioinformatic servers, then synthesized and expressed in
      E. coli. Mice, Guinea pig and, Caco-2 Cell line were used as challenge models for
      EHEC, shigella and ETEC respectively. The chimeric protein induced significant
      immune response and therefore could be a suitable vaccine candidate against these
      three pathogens.

PMID- 29071282
TI  - Identification of miR-24 and miR-137 as novel candidate multiple sclerosis miRNA
      biomarkers using multi-staged data analysis protocol.
AB  - Many studies have investigated misregulation of miRNAs relevant to multiple
      sclerosis (MS) pathogenesis. Abnormal miRNAs can be used both as candidate
      biomarker for MS diagnosis and understanding the disease miRNA-mRNA regulatory
      network. In this comprehensive study, misregulated miRNAs related to MS were
      collected from existing literature, databases and via in silico prediction. A
      multi-staged data integration strategy (including the construction of miRNA-mRNA
      regulatory network and systematic data analysis) was conducted in order to
      investigate MS related miRNAs and their regulatory networks. The final outcome
      was a bi-layer MS related regulatory network constructed with 27 miRNAs (seven of
      them were novel) and 59 mRNA targets. To verify the accuracy of the
      bioinformatics strategy three novel and five previously reported miRNAs from the
      network model were selected for experimental validation using the real-time PCR
      assay. The obtained results proved the accuracy of the network. The expression of
      themiR-24 and miR-137(as novel MS candidate biomarker) and miR-16, and miR-181
      (as previously reported MS candidate biomarker) showed significant deregulation
      in 33 MS patients compared to the control. The optimized data integration
      strategy conducted in this study found two miRNAs (miR-24and miR-16)that can be
      considered as candidate biomarkers for MS and also has the potential to generate
      a regulatory network to aid in further understanding the mechanisms underlying
      this disease.

PMID- 29071283
TI  - Taxonomic review of Argentine mackerel Scomber japonicus (Houttuyn, 1782) by
      phylogenetic analysis.
AB  - Taxonomically, Argentine mackerels were first considered as Scomber japonicus
      marplatensis and later as Scomber japonicus Houttuyn 1782, although, in the last
      years, different studies have suggested that South Atlantic mackerel species
      belongs to Scomber colias Gmelin 1789. These latter results, incorporated in the
      main fish databases (FishBase and Catalog of Fishes), promoted a phylogenetic
      study using cytochrome c oxidase I (COI) gene sequences taken from the Barcode of
      Life (FISH-BOL) database. Thus, 76 sequences of S. japonicus, S. colias, S.
      australasicus and S. scombrus from different regions were used; including 3 from
      Sarda sarda as outgroup. Among S. japonicus selected sequences are those
      corresponding to the Argentine mackerels collected in 2007. Phylogenetic trees
      were obtained by neighbor joining and maximum likelihood methods and a network of
      haplotypes was reconstructed to analyze the relationship between species. The
      results showed the clear differentiation of S. australasicus, S. scombrus and S.
      japonicus from the Pacific while S. japonicus from Argentina was included in the
      S. colias group, with genetic differences corresponding to conspecific
      populations (0.1%). Four of the five Argentine specimens shared the same
      haplotype with S. colias, and none were shared with S. japonicus from the
      Pacific. These results suggest that the current specific name of Argentine
      mackerel S. japonicus should be changed to S. colias, in agreement with several
      genetic studies carried out with species of the genus Scomber.

PMID- 29071284
TI  - Characterizing Cefepime Neurotoxicity: A Systematic Review.
AB  - Neurotoxicity due to cefepime has not been well characterized. We performed a
      systematic review of the literature and included 5 additional cases from our
      center. Of the 198 cases found, the mean age was 67 years and 87% of patients had
      renal dysfunction. The most common clinical features were diminished level of
      consciousness (80%), disorientation/agitation (47%), and myoclonus (40%). It is
      worth noting that nonconvulsive status epilepticus was relatively common with 31%
      of cases, whereas only 11% had convulsive seizures. Single-center estimate of
      incidence was 1 in 480 courses of cefepime. Cefepime neurotoxicity should be
      considered in older patients with renal dysfunction and new onset encephalopathy,
      especially if concurrent myoclonus is present. More work is needed to
      prospectively assess incidence and outcomes related to cefepime neurotoxicity.

PMID- 29071285
TI  - Endpoint or Kinetic Measurement of Hydrogen Sulfide Production Capacity in Tissue
      Extracts.
AB  - Hydrogen sulfide (H2S) gas is produced in cells and tissues via various enzymatic
      processes. H2S is an important signaling molecule in numerous biological
      processes, and deficiencies in endogenous H2S production are linked to
      cardiovascular and other health complications. Quantitation of steady-state H2S
      levels is challenging due to volatility of the gas and the need for specialized
      equipment. However, the capacity of an organ or tissue extract to produce H2S
      under optimized reaction conditions can be measured by a number of current assays
      that vary in sensitivity, specificity and throughput capacity. We developed a
      rapid, inexpensive, specific and relatively high-throughput method for
      quantitative detection of H2S production capacity from biological tissues. H2S
      released into the head space above a biological sample reacts with lead acetate
      to form lead sulfide, which is measured on a continuous basis using a plate
      reader or as an endpoint assay.

PMID- 29071286
TI  - Caenorhabditis elegans Microinjection.
AB  - Microinjection is the most frequently used tool for genetic transformation of the
      nematode Caenorhabditis elegans, facilitating the transgenic expression of genes,
      genome editing by the clustered regularly interspersed short palindromic repeats
      (CRISPR)-Cas9 system, or transcription of dsRNA for RNA intereference (RNAi).
      Exogenous DNA is delivered into the developing oocytes in the germline of adult
      hermaphrodites, which then generate transgenic animals among their offspring. In
      this protocol, we describe the microinjection procedure and the subsequent
      selection of transgenic progeny.

PMID- 29071287
TI  - Collaborative noise data collected from smartphones.
AB  - Noise stands for an important human health and environmental issue. Indeed, noise
      causes annoyance and fatigue, interferes with communication and sleep, damages
      hearing and entails cardiovascular problems (WHO, 2011) [1]. From an
      environmental point of view, noise implies a lessening of both the richness and
      abundance of the animal species, an alteration of the communication, which can
      threaten the reproduction and predation, etc. (Newport et al., 2014; Shannon et
      al., 2014) [2], [3]. Consequently, effects related to environmental noise result
      in a huge cost for society, with 2.2 billion euros in France, for example, for
      the year 2013 (Bourges and Diel, 2015) [4]. In this context, the reduction of
      noise in the environment is a burning issue, which requires, firstly, carrying
      out an evaluation of noise in the environment, and secondly, to establish action
      plans to reduce noise annoyance. With the development of the concept of
      participatory measurement, and considering the extremely large number of people
      equipped with a smartphone while being "in mobility", the use of smartphones is
      potentially a relevant solution to realize a large-scale environmental noise
      evaluation. The data presented hereinafter are collected from the Android
      NoiseCapture application and shared from the OnoMap Spatial Data Infrastructure
      (SDI). The NoiseCapture approach consists in measuring noise along a path, and
      then to share data with the community. This approach has been developed within
      the framework of the European ENERGIC-OD project, which aims at deploying a set
      of Virtual Hubs (VH) to share heterogeneous data with third parties, in respect
      with the European INSPIRE, and at developing new and original services that can
      be useful for the community. The noise data that are acquired by volunteers
      around the world (citizen observations), are organized in three files, containing
      the path of measures (a set of points), standardized noise indicators, noise
      description and other useful variables (GPS accuracy, speed...). These data can
      be very relevant later to propose an environmental noise evaluation, through
      simple or complex treatments.

PMID- 29071288
TI  - Dataset on antioxidant metabolites and enzymes activities of freshly harvested
      sweet cherries (Prunus avium L.) of Campania accessions.
AB  - In this article, we reported the original data obtained by the study of
      metabolites and enzymes involved in sweet cherry antioxidant system. We measured
      hydrogen peroxide (H2O2) and malondialdehyde (MDA), which are indicator of
      oxidative stress. Moreover, we measured the concentration of reduced and oxidized
      ascorbate and glutathione that are involved in ROS detoxification together with
      phenolics, anthocyanins and tocopherols. Among antioxidant enzymes, we analyzed
      the activities of ascorbate peroxidase (APX; EC 1.11.1.11), and the soluble and
      bound forms of polyphenol oxidase (PPO; EC 1.10.3.1) and guaiacol peroxidase
      (POD; EC 1.11.1.7). The data reported in this paper are related to the research
      article "Metabolic characterization and antioxidant activity in sweet cherry
      (Prunus avium L.) Campania accessions", authored by Mirto et al. (2018) [1].

PMID- 29071289
TI  - Data on fluoride concentration levels in cold and warm season in rural area of
      Shout (West Azerbaijan, Iran).
AB  - The aim of this study was to determine the concentration of fluoride in drinking
      water, the distribution system, in 22 villages in Shout (A city in West
      Azerbaijan province). Sampling of springs and underground water was carried out
      in two warm and cold seasons. Fluoride concentration were determined through
      spectrophotometer with a model, DR/5000.The fluoride concentration were compared
      with Iranian standards and WHO guidelines for drinking water.

PMID- 29071290
TI  - Data from a multidisciplinary poll of 178 expert physicians on the usage of non
      vitamin K Oral Anticoagulants in patients with atrial fibrillation and venous
      thromboembolism.
AB  - This data article contains data from a multidisciplinary questionnaires filled in
      by 178 expert physicians on the usage of non-vitamin K Oral Anticoagulants in
      patients with atrial fibrillation (AF) and for the treatment of patients with
      venous thromboembolism (VTE). The questionnaire consists of 9 statements of
      clinical complex AF and VTE cases and informative campaign on antithrombotic
      therapy for stroke prevention in AF. The data are potentially valuable for the
      scientific community, showing the doubts of different specialists (Internists,
      Pneumologists, Geriatricians, Cardiologists and Neurologists) with a large
      experience in prescribing oral anticoagulation in difficult AF and VTE cases (see
      full list of participants provided). The data obtained in some particular
      clinical cases such as CHA2DS2-VASc=1, comorbid coronary artery disease, frailty,
      advanced age, risk of falling and prior haemorrhagic stroke, can be compared with
      indications from published guidelines and recommendations for future insight and
      to be considered as a benchmark for future trials in the area or oral
      anticoagulation for AF and VTE. The data concerning informative campaign on
      antithrombotic therapy for stroke prevention showed the expert panel agreement on
      the inclusion of self monitoring of heart rhythm by pulse taking in subjects
      older than 64 years of age (81% agreement, item 3); knowledge that the risk of
      stroke associated with AF is almost twice the risk associated with hypertension
      (95% agreement, item 4); knowledge that the CHA2DS2-VASc score exerts a higher
      influence on stroke risk compared to AF duration (92% agreement, item 5);
      knowledge that stroke prevention in AF with a NOAC is more effective, does not
      cause any higher bleeding risk, and is equally simple compared to aspirin
      treatment (91% agreement, item 6). Data on strategies to optimise appropriate
      prescription of antithrombotic therapy showed agreement on the utility of short
      television advertisements about the risks of stroke associated with AF (79%
      agreement, item 8), on a campaign encouraging regular control of cardiac rhythm
      by pulse taking (77% agreement, item 1), on a campaign reporting the advantages
      of anticoagulation over no antithrombotic therapy (98% agreement, item 2) or of
      NOACs over aspirin (96% agreement, item 3) or on the practical use of NOAC (93%
      agreement, item 6) or on stroke and bleeding risk scores (87% agreement, item 7).
      See Colonna et al. (2017) [1] for further interpretation and discussion.

PMID- 29071291
TI  - Brief data report on prototype of moral personality and environmentalism.
AB  - The data presented here was partially published in the article "Are Environmental
      Issues Moral Issues? Moral Identity in Relation to Protecting the Natural World"
      (Jia et al., 2017) [1]. The data was collected at State University of New York at
      Oneonta in 2016. It included a self-report questionnaire of moral identity,
      generativity, community engagement, environmental involvement, environmental
      identity, and demographic information.

PMID- 29071292
TI  - The data of establishing a three-dimensional culture system for in vitro
      recapitulation and mechanism exploration of tumor satellite formation during
      cancer cell transition.
AB  - Tumor satellite formation is an indicator of cancer invasiveness and correlates
      with recurrence, metastasis, and poorer prognosis. By analyzing pathological
      specimens, tumor satellites formed at the tumor-host interface reflect the
      phenomena of epithelial-mesenchymal transition. It is impossible to reveal the
      dynamic processes and the decisive factors of tumor satellite formation using
      clinicopathological approaches alone. Therefore, establishment of an in vitro
      system to monitor the phenomena is important to explicitly elucidate underlying
      mechanisms. In this study, we explored the feasibility of creating an in vitro
      three-dimensional collagen culture system to recapitulate the process of tumor
      satellite formation. This data presented here are referred to the research
      article (Chen et al., 2017) [1]. Using this model, the dynamic process of tumor
      satellite formation could be recapitulated in different types of human cancer
      cells. Induced by calcium deprivation, the treated cells increased the incidence
      and migratory distance of tumor satellites. E-cadherin internalization and
      invadopodia formation were enhanced by calcium deprivation and were associated
      with cellular dynamic change during tumor satellite formation. The data confirmed
      the utility of this culture system to recapitulate dynamic cellular alteration
      and to explore the potential mechanisms of tumor satellite formation.

PMID- 29071293
TI  - Secondary phosphorylation in myocytes expressing FLAG-tagged and non-tagged
      phospho-mimetic cardiac troponin I.
AB  - Secondary phosphorylation develops in myocytes expressing phospho-mimetic cardiac
      troponin I (cTnI) but it is not known whether multiple substitutions (e.g.
      cTnISDTD and cTnIS4D) cause preferential phosphorylation of the remaining
      endogenous or the phospho-mimetic cTnI in intact myocytes. Western analysis was
      performed to determine whether the FLAG/total cTnI ratios are similar for
      phosphorylated versus total cTnI in myocytes expressing phospho-mimetic cTnI with
      Asp(D) substitutions at S43/45 plus S23/24 (cTnIS4D) or T144 (cTnISDTD).
      Representative Western analysis of phosphorylated S23/24 (p-S23/24) and S150 (p
      S150) are presented along with re-probes using an antibody which detects all cTnI
      (MAB1691 Ab). The level of p-S150 also is compared to results obtained using
      single S43D and/or S45D phospho-mimetic substitutions. These results are
      discussed in more detail in Lang et al. [1].

PMID- 29071294
TI  - Data on the expression of leptin and leptin receptor in the dorsal root ganglion
      and spinal cord after preganglionic cervical root avulsion.
AB  - Leptin (Lep) is mainly, although not exclusively, secreted by adipocytes. In
      addition to regulating lipid metabolism, it is also a proinflammatory factor and
      involved in the development of neuropathic pain after peripheral nerve injuries
      (PNI) (Lim et al., 2009; Maeda et al., 2009) [1,2]. Leptin or its messenger
      ribonucleic acid expression has been found in various brain regions normally and
      in the dorsal horn after PNI (Lim et al., 2009; Ur et al., 2002; La Cava et al.,
      2004; White et al., 2004) [1,[3], [4], [5]]. However, the expression pattern of
      Lep and Leptin receptor (LepR) after preganglionic cervical root avulsion (PCRA)
      is still unknown. We provide data in this article related to Chang et al. (2017)
      [6]. Here, our data showed a profound Lep and LepR expression in the neurons of
      dorsal root ganglion (DRG) after PCRA. Moreover, the expression of Lep and LepR
      were also identified in significant portions of the neurons and microglia located
      in the dorsal horn. The roles of these increased expressions in the development
      of neuropathic pain after PCRA deserve further study.

PMID- 29071295
TI  - Data of first de-novo transcriptome assembly of a non-model species, hawksbill
      sea turtle, Eretmochelys imbricate, nesting of the Colombian Caribean.
AB  - The hawksbill sea turtle, Eretmochelys imbricata, is an endangered species of the
      Caribbean Colombian coast due to anthropic and natural factors that have
      decreased their population levels. Little is known about the genes that are
      involved in their immune system, sex determination, aging and others important
      functions. The data generated represents RNA sequencing and the first de-novo
      assembly of transcripts expressed in the blood of the hawksbill sea turtle. The
      raw FASTQ files were deposited in the NCBI SRA database with accession number
      SRX2653641. A total of 5.7 Gb raw sequence data were obtained, corresponding to
      47,555,108 raw reads. Trinity was used to perform a first de-novo assembly, and
      we were able to identify 47,586 transcripts of the female hawksbill turtle
      transcriptome with an N50 of 1100 bp. The obtained transcriptome data will be
      useful for further studies of the physiology, biochemistry and evolution in this
      species.

PMID- 29071296
TI  - Data on peptides identified by mass spectrometry analysis of in vitro DYRK1A
      mediated phosphorylation sites on GLI1.
AB  - The data presented in this article support the accompanying research article
      "Identification of a DYRK1A-mediated phosphorylation site within the nuclear
      localization sequence of the hedgehog transcription factor GLI1" (Ehe et al.,
      2017) [1]. Although it has been demonstrated that DYRK1A (dual-specificity
      tyrosine-regulated kinase 1A) can phosphorylate the hedgehog pathway
      transcription factor GLI1 (GLIoma-associated oncogene homolog 1) and promote its
      nuclear localization, the DYRK1A-mediated sites of phosphorylation on GLI1
      involved were not fully known. This article details the mass spectrometry methods
      and resulting dataset for the peptides identified from GLI1 when incubated with
      DYRK1A under varying conditions. The data include details of sequence coverage
      and all phospho-peptides identified.

PMID- 29071297
TI  - Pollution load index for heavy metals in Mian-Ab plain soil, Khuzestan, Iran.
AB  - Soil pollution by heavy metals is a major concern in agricultural area. Potential
      impact of heavy metals in agricultural soil on human health by accumulating in
      food chain demonstrated elsewhere. In this regard Mian-Ab plain as a major
      agricultural site of Khuzestan province considered for Arsenic, cadmium and lead
      concentration as the main potential toxic pollutants in soil. 50 topsoil samples
      were collected and analyzed by inductively coupled plasma mass spectrometry (ICP
      MS). Also Contamination level of selected heavy metals in Mian-Ab Plain, was
      assessed by single factor contaminant index (PI) and pollution load index (PLI).
      Results show mean concentration of arsenic, cadmium and lead were 2.52, 0.30 and
      7.21 mg kg-1. Base on PLI results 12 point (24%) of the studied area show
      moderately polluted and 38 point (76%) show unpolluted area.

PMID- 29071298
TI  - Unique Configurations of Compression and Truncation of Neuronal Activity Underlie
      l-DOPA-Induced Selection of Motor Patterns in Aplysia.
AB  - A key issue in neuroscience is understanding the ways in which neuromodulators
      such as dopamine modify neuronal activity to mediate selection of distinct motor
      patterns. We addressed this issue by applying either low or high concentrations
      of l-DOPA (40 or 250 MUM) and then monitoring activity of up to 130 neurons
      simultaneously in the feeding circuitry of Aplysia using a voltage-sensitive dye
      (RH-155). l-DOPA selected one of two distinct buccal motor patterns (BMPs):
      intermediate (low l-DOPA) or bite (high l-DOPA) patterns. The selection of
      intermediate BMPs was associated with shortening of the second phase of the BMP
      (retraction), whereas the selection of bite BMPs was associated with shortening
      of both phases of the BMP (protraction and retraction). Selection of intermediate
      BMPs was also associated with truncation of individual neuron spike activity
      (decreased burst duration but no change in spike frequency or burst latency) in
      neurons active during retraction. In contrast, selection of bite BMPs was
      associated with compression of spike activity (decreased burst latency and
      duration and increased spike frequency) in neurons projecting through specific
      nerves, as well as increased spike frequency of protraction neurons. Finally,
      large-scale voltage-sensitive dye recordings delineated the spatial distribution
      of neurons active during BMPs and the modification of that distribution by the
      two concentrations of l-DOPA.

PMID- 29071299
TI  - Noradrenergic Regulation of Central Amygdala in Aversive Pavlovian-to
      Instrumental Transfer.
AB  - The neural mechanisms through which a Pavlovian conditioned stimulus (CS) elicits
      innate defense responses are well understood. But a Pavlovian CS can also
      invigorate ongoing instrumental responding, as shown by studies of aversive
      Pavlovian-to-instrumental transfer (PIT). While the neural circuitry of
      appetitive PIT has been studied extensively, little is known about the brain
      mechanisms of aversive PIT. We recently showed the central amygdala (CeA) is
      essential for aversive PIT. In the current studies, using pharmacology and
      designer receptors in rodents, we demonstrate that noradrenergic (NE) activity
      negatively regulates PIT via brainstem locus coeruleus (LC) activity and LC
      projections to CeA. Our results provide evidence for a novel pathway through
      which response modulation occurs between brainstem neuromodulatory systems and
      CeA to invigorate adaptive behavior in the face of threat.

PMID- 29071301
TI  - Action Monitoring Cortical Activity Coupled to Submovements.
AB  - Numerous studies have examined neural correlates of the human brain's action
      monitoring system during experimentally segmented tasks. However, it remains
      unknown how such a system operates during continuous motor output when no
      experimental time marker is available (such as button presses or stimulus onset).
      We set out to investigate the electrophysiological correlates of action
      monitoring when hand position has to be repeatedly monitored and corrected. For
      this, we recorded high-density electroencephalography (EEG) during a visuomotor
      tracking task during which participants had to follow a target with the mouse
      cursor along a visible trajectory. By decomposing hand kinematics into naturally
      occurring periodic submovements, we found an event-related potential (ERP) time
      locked to these submovements and localized in a sensorimotor cortical network
      comprising the supplementary motor area (SMA) and the precentral gyrus.
      Critically, the amplitude of the ERP correlated with the deviation of the cursor,
      110 ms before the submovement. Control analyses showed that this correlation was
      truly due to the cursor deviation and not to differences in submovement
      kinematics or to the visual content of the task. The ERP closely resembled those
      found in response to mismatch events in typical cognitive neuroscience
      experiments. Our results demonstrate the existence of a cortical process in the
      SMA, evaluating hand position in synchrony with submovements. These findings
      suggest a functional role of submovements in a sensorimotor loop of periodic
      monitoring and correction and generalize previous results from the field of
      action monitoring to cases where action has to be repeatedly monitored.

PMID- 29071300
TI  - Dopamine D2 Receptors in the Paraventricular Thalamus Attenuate Cocaine Locomotor
      Sensitization.
AB  - Alterations in thalamic dopamine (DA) or DA D2 receptors (D2Rs) have been
      measured in drug addiction and schizophrenia, but the relevance of thalamic D2Rs
      for behavior is largely unknown. Using in situ hybridization and mice expressing
      green fluorescent protein (GFP) under the Drd2 promoter, we found that D2R
      expression within the thalamus is enriched in the paraventricular nucleus (PVT)
      as well as in more ventral midline thalamic nuclei. Within the PVT, D2Rs are
      inhibitory as their activation inhibits neuronal action potentials in brain
      slices. Using Cre-dependent anterograde and retrograde viral tracers, we further
      determined that PVT neurons are reciprocally interconnected with multiple areas
      of the limbic system including the amygdala and the nucleus accumbens (NAc).
      Based on these anatomical findings, we analyzed the role of D2Rs in the PVT in
      behaviors that are supported by these areas and that also have relevance for
      schizophrenia and drug addiction. Male and female mice with selective
      overexpression of D2Rs in the PVT showed attenuated cocaine locomotor
      sensitization, whereas anxiety levels, fear conditioning, sensorimotor gating,
      and food-motivated behaviors were not affected. These findings suggest the
      importance of PVT inhibition by D2Rs in modulating the sensitivity to cocaine, a
      finding that may have novel implications for human drug use.

PMID- 29071302
TI  - Paraquat and MPTP induce neurodegeneration and alteration in the expression
      profile of microRNAs: the role of transcription factor Nrf2.
AB  - Both transcription factors (TFs) and microRNAs (miRNAs) can exert a widespread
      impact on gene expression. In the present study, we investigated the role of Nrf2
      in paraquat-induced intracorporeal neurodegeneration and miRNA expression by
      exposing Nrf2 wild-type and knockout mice to paraquat (PQ) or 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). Exposure to 10 mg/kg PQ or 30 mg/kg MPTP
      caused damage to nerve cells in the substantia nigra (SN) in both Nrf2 (+/+) and
      Nrf2 (-/-) ICR mice, which included cell morphological changes, detectable
      apoptosis and a significant reduction in the number of dopaminergic (DA) neurons.
      When mice were exposed to the same PQ dose of 10 mg/kg, significant fewer
      tyrosine hydroxylase (TH)-positive DA neurons were observed in the Nrf2 (-/-)
      mice than that in the Nrf2 (+/+) mice. Both Nrf2 deficiency and PQ or MPTP
      exposure could alter miRNA expression profile in the SN, suggesting the potential
      involvement of Nrf2 in the PQ-induced or MPTP-induced miRNA expression
      alteration. The expression of miR-380-3p was altered by the Nrf2-MPTP interaction
      effect. miR-380-3p/Sp3-mRNA pathway is likely part of the mechanism of MPTP
      induced neurodegeneration. Collectively, our results corroborated the protective
      role of Nrf2 and also demonstrated the essential interaction of Nrf2 with miRNAs
      in intracorporal neurodegeneration induced by neurotoxicants.

PMID- 29071304
TI  - Esophageal Xanthoma: Presence of M2 Macrophages Suggests Association with Late
      Inflammatory and Reparative Processes.
AB  - Esophageal xanthoma is a rare lesion which is an asymptomatic small yellowish
      polyp, and most of the reported cases were solitary lesion. Histologically,
      aggregations of foam cells are found under the papillary hypertrophic squamous
      epithelium and the foam cells express CD68. The etiology of esophageal xanthoma
      is unknown. The focal irritation of the esophageal mucosa and infiltrated
      inflammatory cells are presumed to contribute to its pathogenesis. Although the
      pathogenesis may be associated with inflammation, the type and nature of the
      macrophages remain unclear. Here we report a 46-year-old male with esophageal
      xanthoma, which was incidentally found by endoscopy. Histologically, acute
      inflammation was not noted, and immunohistochemistry revealed that the foam cells
      seen in this case of esophageal xanthoma expressed increased levels of M2
      macrophage markers. These findings suggest that esophageal xanthoma is associated
      with late inflammatory and reparative processes long after the initial
      inflammation of esophageal squamous epithelium.

PMID- 29071306
TI  - Labour force activity after 65: what explain recent trends in Denmark, Germany
      and Sweden?
AB  - In most OECD member countries labour force attachment, has increased in recent
      years not only in the age groups 60-64 years but also among people 65 years and
      older. Focus in this paper is on the trend in older workers' labour force
      participation in Denmark, Germany and Sweden since 2004. Main emphasis is given
      to people aged 65-69 years eligible for social security retirement programs from
      age 65. The gender aspect is included to accommodate different trends for women
      and men. To explain country differences in trends, the importance of changes in
      retirement policies of relevance for this age group and cohort relevant changes
      in education and health is examined and discussed. Further, country differences
      in the impact from education and health is examined. Results show that the
      largest increase in labour force participation among people aged 65-69 years has
      taken place in Sweden following by Germany, while the increase in Denmark is
      rather small. While the increase in Germany mainly seems to be a result of policy
      reforms, the increase in Sweden appear to be a result of a combination of policy
      changes and an increasing educational level. Financial incentives seem most
      important in Germany and only of minor importance in Denmark, where policy
      changes directed towards individuals above the age of 65 appear to have been too
      small so far to affect retirement behaviour significantly.

PMID- 29071305
TI  - Absolute Reliability and Concurrent Validity of Hand Held Dynamometry and
      Isokinetic Dynamometry in the Hip, Knee and Ankle Joint: Systematic Review and
      Meta-analysis.
AB  - The purpose of the study is to establish absolute reliability and concurrent
      validity between hand-held dynamometers (HHDs) and isokinetic dynamometers (IDs)
      in lower extremity peak torque assessment. Medline, Embase, CINAHL databases were
      searched for studies related to psychometric properties in muscle dynamometry.
      Studies considering standard error of measurement SEM (%) or limit of agreement
      LOA (%) expressed as percentage of the mean, were considered to establish
      absolute reliability while studies using intra-class correlation coefficient
      (ICC) were considered to establish concurrent validity between dynamometers. In
      total, 17 studies were included in the meta-analysis. The COSMIN checklist
      classified them between fair and poor. Using HHDs, knee extension LOA (%) was
      33.59%, 95% confidence interval (CI) 23.91 to 43.26 and ankle plantar flexion LOA
      (%) was 48.87%, CI 35.19 to 62.56. Using IDs, hip adduction and extension; knee
      flexion and extension; and ankle dorsiflexion showed LOA (%) under 15%. Lower
      hip, knee, and ankle LOA (%) were obtained using an ID compared to HHD. ICC
      between devices ranged between 0.62, CI (0.37 to 0.87) for ankle dorsiflexion to
      0.94, IC (0.91to 0.98) for hip adduction. Very high correlation were found for
      hip adductors and hip flexors and moderate correlations for knee
      flexors/extensors and ankle plantar/dorsiflexors.

PMID- 29071307
TI  - Skill-building through Task-Oriented Motor Practice (STOMP) intervention for
      activities of daily living: study protocol for a randomized, single blinded
      clinical trial.
AB  - BACKGROUND: Progressive disability in activities of daily living (ADL) is
      inevitable for people with Alzheimer's disease and related dementias (ADRD).
      Attempts to slow or prevent ADL disability have been unsuccessful despite making
      progress in behavioral training methods. Missing from this research is an
      emphasis on how we maximize a patient's engagement during training and the
      rigorous examination of implementation protocols (dosing and training methods)
      which may advantage learning in people with ADRD. Our team addressed this gap
      with the development of the STOMP (Skill-building through Task-Oriented Motor
      Practice) intervention which creates methods for obtaining ADL goals that support
      "personhood" and tests high-intensity protocols that appear to advantage learning
      and sustained learning over time. Through this study, we aim to evaluate
      differential outcomes by dose levels as well as assess the moderating effects of
      attention to task during training. METHODS/DESIGN: Randomized-controlled trial
      with 32 participants with dementia assigned to either the original, intensive
      STOMP protocol (3 hours/day, 5 days/week for 2 weeks) or a less-intensive STOMP
      protocol (1 hour/day, 2 days/week for 2 weeks) delivered by an occupational
      therapy assistant in the home. ADL training is delivered using motor learning
      theory techniques of blocked practice, continuous verbal praise, errorless
      learning and intense dosing schedules. Inclusion criteria: English speaking,
      adults 50-80 years old that live with a legally-authorized representative that
      can provide consent, who can follow a one-step command, have three ADL goals they
      want to address and can participate in an intense therapy protocol. Exclusions
      include diagnoses of Creutzfeldt-Jakob Dementia, delirium or receptive/global
      aphasia. Recruitment will occur through direct mailing, physician referral and
      media/support group presentations. Blinded occupational therapists will complete
      baseline, post-intervention and 3-month follow-up assessments in the home.
      Repeated measures ANOVA and graphs will be used to interpret and display results.
      DISCUSSION: Through this protocol, we will examine differential outcomes by dose
      for the STOMP ADL intervention. Our results will inform dosing parameters for
      future intervention studies for people with ADRD. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT02356055. ETHICAL APPROVAL: This study protocol
      was approved by the University of Oklahoma Health Sciences Center Institutional
      Review Board (#4648) and will be performed in accordance with the Declaration of
      Helsinki.

PMID- 29071314
TI  - 2,2'-Biphen[n]arenes (n = 4-8): one-step, high-yield synthesis, and host-guest
      properties.
AB  - A new family of biphen[n]arenes (n = 4-8) with 2,2'-disubstituents (2,2'-BPns)
      has been designed and synthesized. The host-guest properties of the 2,2'-BPns
      have been examined; they exhibit strong binding affinities towards selected
      organic cationic guests.

PMID- 29071308
TI  - A Text-Mining Framework for Supporting Systematic Reviews.
AB  - Systematic reviews (SRs) involve the identification, appraisal, and synthesis of
      all relevant studies for focused questions in a structured reproducible manner.
      High-quality SRs follow strict procedures and require significant resources and
      time. We investigated advanced text-mining approaches to reduce the burden
      associated with abstract screening in SRs and provide high-level information
      summary. A text-mining SR supporting framework consisting of three self-defined
      semantics-based ranking metrics was proposed, including keyword relevance,
      indexed-term relevance and topic relevance. Keyword relevance is based on the
      user-defined keyword list used in the search strategy. Indexed-term relevance is
      derived from indexed vocabulary developed by domain experts used for indexing
      journal articles and books. Topic relevance is defined as the semantic similarity
      among retrieved abstracts in terms of topics generated by latent Dirichlet
      allocation, a Bayesian-based model for discovering topics. We tested the proposed
      framework using three published SRs addressing a variety of topics (Mass Media
      Interventions, Rectal Cancer and Influenza Vaccine). The results showed that when
      91.8%, 85.7%, and 49.3% of the abstract screening labor was saved, the recalls
      were as high as 100% for the three cases; respectively. Relevant studies
      identified manually showed strong topic similarity through topic analysis, which
      supported the inclusion of topic analysis as relevance metric. It was
      demonstrated that advanced text mining approaches can significantly reduce the
      abstract screening labor of SRs and provide an informative summary of relevant
      studies.

PMID- 29071309
TI  - Kernel-Regularized ICA for Computing Functional Topography from Resting-state
      fMRI.
AB  - Topographic regularity is a fundamental property in brain connectivity. In this
      work, we present a novel method for studying topographic regularity of functional
      connectivity based on resting-state fMRI (rfMRI), which is widely available and
      easy to acquire in large-scale studies. The main idea in our method is the
      incorporation of topographically regular structural connectivity for independent
      component analysis (ICA). This is enabled by the recent development of novel
      tractography and tract filtering algorithms that can generate highly organized
      fiber bundles connecting different brain regions. By leveraging these cutting
      edge tractography algorithms, here we develop a kernel-regularized ICA method for
      the extraction of functional topography with rfMRI signals. In our experiments,
      we use rfMRI scans of 35 unrelated, right-handed subjects from the Human
      Connectome Project (HCP) to study the functional topography of the motor cortex.
      We first demonstrate that our method can generate functional connectivity maps
      with more regular topography than conventional group ICA. We also show that the
      components extracted by our algorithm are able to capture co-activation patterns
      that respect the organized topography of the motor cortex across the hemisphere.
      Finally, we show that our method achieves improved reproducibility as compared to
      conventional group ICA.

PMID- 29071303
TI  - Cell Based Therapeutic Approach in Vascular Surgery: Application and Review.
AB  - Multipotent stem cells - such as mesenchymal stem/stromal cells and stem cells
      derived from different sources like vascular wall are intensely studied to try to
      rapidly translate their discovered features from bench to bedside. Vascular wall
      resident stem cells recruitment, differentiation, survival, proliferation, growth
      factor production, and signaling pathways transduced were analyzed. We studied
      biological properties of vascular resident stem cells and explored the
      relationship from several factors as Matrix Metalloproteinases (MMPs) and
      regulations of biological, translational and clinical features of these cells. In
      this review we described a translational and clinical approach to Adult Vascular
      Wall Resident Multipotent Vascular Stem Cells (VW-SCs) and reported their
      involvement in alternative clinical approach as cells based therapy in vascular
      disease like arterial aneurysms or peripheral arterial obstructive disease.

PMID- 29071315
TI  - Catalyst free annulative thioboration of unfunctionalized olefins.
AB  - A direct and catalyst-free annulative thioboration of unfunctionalized olefins
      has been developed. In the presence of BCl3 as the sole boron source, the boryl
      group and thiol group are added to the C-C double bonds simultaneously. The
      boronic acids obtained can be protected to form synthetically ubiquitous pinacol
      boronate esters.

PMID- 29071316
TI  - Off-center motion of a trapped elastic capsule in a microfluidic channel with a
      narrow constriction.
AB  - Owing to their significance in capsule-related engineering and biomedical
      applications, a number of studies have considered the dynamics of elastic
      capsules flowing in constricted microchannels. However, these studies have
      focused on capsules moving along the channel centerline. In the present study, we
      numerically investigate the transient motion of an elastic capsule in a
      microfluidic channel with a rectangular constriction, which is initially trapped
      at the constriction inlet while off the channel centerline (i.e., on the channel
      bottom-wall). Under the push of the surrounding flow, the capsule can squeeze
      into the constriction, but only if the capsule deformability or the constriction
      size is sufficiently large. We find that the critical capillary number leading to
      the penetration of the capsule into the constriction is larger for off-centerline
      capsules compared to centered capsules. The centered capsule is stationary at the
      steady state when it remains stuck at the constriction; in contrast, the off
      centerline capsule is not stationary but exhibits a tank-treading motion, i.e.,
      its overall shape maintains a nonspherical shape with a protrusion into the
      constriction while its membrane exhibits a continuous rotation. Further, we
      examine the dependence of the capsule motion type, capsule deformation degree and
      membrane tension distribution on the capillary number (measuring the effects of
      flow strength and membrane mechanics) and constriction geometries (including the
      constriction height and width). Finally, we discuss the mechanism governing the
      capsule motion by analyzing the hydrodynamic forces acting on the capsule. The
      shear force acting on the capsule top owing to the fluid flow in the gap between
      the capsule top and the channel top-wall is the main source inducing the membrane
      tank-treading rotation.

PMID- 29071321
TI  - Chemical surface exchange of oxygen on CeO2-delta in an O2/H2O atmosphere.
AB  - The chemical surface reaction rate constant controlling the change of oxidation
      state of undoped ceria, kChem, was measured at 1400  degrees C in the range of
      (~0 <= (pH2O/atm) <= 0.163(9)) and (10-3.85 <= (pO2/atm) <= 10-2.86) via the
      electrical conductivity relaxation method. In humidified atmospheres, kChem is
      fully described as the sum of kChem,O2 and kChem,H2O, which are, respectively,
      the rate constants for oxidation by O2 and by H2O alone. Using measurements under
      appropriately controlled gas conditions, the total rate constant is found to
      follow the correlation kChem/cm s-1 = 10-(1.35+/-0.07) * (pO2/atm)0.72+/-0.02 +
      10-(3.85+/-0.03) * (pH2O/atm)0.36+/-0.03 where the pO2 and pH2O values of
      relevance are explicitly those of the final gas condition. The results suggest
      that at such high temperatures, the concentrations of surface adsorbed species
      are too low to influence the independent reaction pathways.

PMID- 29071320
TI  - Altering surface fluctuations by blending tethered and untethered chains.
AB  - "Partially tethering" a thin film of a polymer melt by covalently attaching to
      the substrate a fraction of the chains in an unentangled melt dramatically
      increases the relaxation time of the surface height fluctuations. This phenomenon
      is observed even when the film thickness, h, is 20 times the unperturbed chain
      radius, Rg,tethered, of the tethered chains, indicating that partial tethering is
      more influential than any physical attraction with the substrate. Furthermore, a
      partially tethered layer of a low average molecular weight of 5k showed much
      slower surface fluctuations than did a reference layer of pure untethered chains
      of much greater molecular weight (48k), so the partial tethering effect is
      stronger than the effects of entanglement and increase in glass transition
      temperature, Tg, with molecular weight. Partial tethering offers a means of
      tailoring these fluctuations which influence wetting, adhesion, and tribology of
      the surface.

PMID- 29071322
TI  - Understanding chain folding morphology of semicrystalline polymers based on a rod
      coil multiblock model.
AB  - We employ a rod-coil multiblock molecular chain model to investigate chain
      folding behavior, which is a significant characteristic in semicrystalline
      polymers, by using the method of self-consistent field theory (SCFT). Polymer
      chains with different conformations in crystalline and amorphous regions are
      described by rigid rod chains and flexible Gaussian chains, respectively. At
      present, we concentrate on the thermodynamic behaviors of polymer semi-crystals
      after the formation of the initial lamellar crystals. A new mechanism for
      lamellar thickening is proposed to realize that the end of lamellar thickening
      depends on the crystallinity degree. In other words, it is impossible for
      lamellae to develop into extended-chain crystals by means of lamellar thickening
      if crystallinity is limited to a certain degree. We further discuss the
      competition between crystalline and amorphous regions and its influence on
      crystallization behaviors, such as the formation of double lamellae, chain tilt,
      the anomalies and adjacent re-entry. The synergistic influences of the driving
      force of crystallization, interfacial energy and crystallinity degree on chain
      folding behavior are also investigated when the density anomalies in amorphous
      regions are excluded. Our model demonstrates advantages in accurately describing
      the mesoscopic layered structures of semicrystalline polymers based upon a
      microscopic chain model and provides at least a semi-quantitative thermodynamic
      picture for chain folding.

PMID- 29071323
TI  - Does Flory-Rehner theory quantitatively describe the swelling of thermoresponsive
      microgels?
AB  - The swelling of thermoresponsive microgels is widely modelled through Flory
      Rehner theory, which combines Flory-Huggins solution thermodynamics with the
      affine network model of elasticity. While it has been shown that FR theory
      closely follows experimental results for a range of systems, the large number of
      free parameters required to fit size vs. temperature data make a proper
      evaluation of the theory difficult. In order to test the applicability of FR
      theory to microgel particles, we analyse viscosity and light scattering data for
      PNIPAM microgels as a function of temperature, cross-linking degree (f) and molar
      mass. In the collapsed state, the polymer volume fraction is estimated to be phiC
      ? 0.44, independent of cross linking degree and molar mass. Fixing phiC, f and
      the theta temperature to independent estimates, the FR model appears to describe
      microgel swelling well, particularly for high cross-linking densities. Estimates
      for the various fit parameters differ from earlier reports by an order of
      magnitude. A comparison of the chi parameter obtained from FR theory with values
      for the linear polymer reveals that the agreement between experiment and theory
      is somewhat fortuitous. Although the FR model can accurately describe
      experimental data, the accuracy of the obtained fit parameters is significantly
      poorer.

PMID- 29071325
TI  - Current-voltage characteristics and electroresistance in LaMnO3
      delta/La0.7Ca0.3MnO3/LaAlO3 thin film composites.
AB  - In this communication, we report results of the electrical transport properties
      across the interface of composites consisting of n-type LaMnO3-delta (LMO) and p
      type La0.7Ca0.3MnO3 (LCMO) manganites grown on LaAlO3 (LAO) single crystalline
      substrates using low cost wet chemical solution deposition (CSD) and
      sophisticated, well-controlled dry chemical vapor deposition (CVD) chemical
      techniques. The XRD phi-scan studies reveal the single crystalline nature of both
      bilayered composites, with parallel epitaxial growth of LMO and LCMO layers onto
      the LAO substrate. The valence states of Mn ions in both layers of both
      composites were identified by performing X-ray photoelectron spectroscopy (XPS).
      The I-V characteristics of the LMO/LCMO interfaces show strong backward diode
      like behavior at higher applied voltages well above the crossover voltage (VNB).
      Below VNB, the interfaces demonstrate normal diode-like characteristics
      throughout the studied temperature range. The electric field-induced modulation
      of the LMO/LCMO junction resistance of the interfaces has been observed. Electric
      field-dependent electroresistance (ER) modifications at different temperatures
      have also been studied. The electrical transport properties have been discussed
      in the context of various mechanisms, such as charge injection, tunneling,
      depletion region modification and thermal processes across the interface. The
      effects of structurally and chemically developed sharp interfaces between the LMO
      and LCMO layers on the transport properties of the presently studied bilayered
      thin film composites have been discussed on the basis of correlation between the
      physicochemical characterization and charge transport behavior. A comparison of
      different aspects of the transport properties has been presented in the context
      of the structural strain and crystallinity of the composites grown using both wet
      and dry chemical techniques.

PMID- 29071324
TI  - Phenolic condensation and facilitation of fluorescent carbon dot formation: a
      mechanism study.
AB  - Fluorescent carbon dots have received considerable attention as a result of their
      accessibility and potential applications. Although several prior studies have
      demonstrated that nearly any organic compound can be converted into carbon dots
      by chemical carbonization processes, mechanisms explaining the formation of
      carbon dots still remain unclear. Herein, we propose a seed-growth mechanism of
      carbon dot formation facilitated by ferulic acid, a widespread and naturally
      occurring phenolic compound in the seeds of Ocimum basilicum (basil). Ferulic
      acid triggers the local condensation of polysaccharide chains and forms catalytic
      core regions resulting in nanoscale carbonization. Our study indicates that
      carbon dots generated from natural sources might share the similar mechanism of
      phenolic compound mediated nanoscale condensation followed by core carbonization.

PMID- 29071326
TI  - Access to the meta position of arenes through transition metal catalysed C-H bond
      functionalisation: a focus on metals other than palladium.
AB  - The elaboration of simple arenes in order to access more complex substitution
      patterns is a crucial endeavor for synthetic chemists, given the central role
      that aromatic rings play in all manner of important molecules. Classical methods
      are now routinely used alongside stoichiometric organometallic approaches and,
      most recently, transition metal catalysis in the range of methodologies that are
      available to elaborate arene C-H bonds. Regioselectivity is an important
      consideration when selecting a method and, of all those available, it is arguably
      those that target the meta position that are fewest in number. The rapid
      development of transition metal-catalysed C-H bond functionalisation over the
      last few decades has opened new possibilities for meta-selective C-H
      functionalisation through the diverse reactivity of transition metals and their
      compatibility with a wide range of directing groups. The pace of discovery of
      such processes has grown rapidly in the last five years in particular and it is
      the purpose of this review to examine these but in doing so to place the focus on
      metals other than palladium, the specific contributions of which have been very
      recently reviewed elsewhere. It is hoped this will serve to highlight to the
      reader the breadth of current strategies and mechanisms that have been used to
      tackle this challenge, which may inspire further progress in the field.

PMID- 29071328
TI  - Strain engineering, efficient excitonic photoluminescence, and exciton funnelling
      in unmodified MoS2 nanosheets.
AB  - We established locally varying strain fields in unmodified MoS2 nanosheets. The
      approach relies on dry release in place of multilayer MoS2 on textured Si
      substrates. By this process we demonstrated intense photoluminescence, a ~70 meV
      decrease of the transition energy, and exciton funneling in ~4 nm-thick MoS2
      films.

PMID- 29071329
TI  - Optically active histidin-2-ylidene stabilised gold nanoparticles.
AB  - Drawing from the natural amino acid chiral pool, l and d histidines were utilized
      as chiral NHC ligands in the synthesis of NHC-stabilized chiroptical gold
      nanoparticles. Centrifugal size selection afforded monodisperse gold
      nanoparticles which display mirrored signals in CD spectroscopy.

PMID- 29071330
TI  - Using Epidemiology to Determine Surgical Needs in Low-Resource Settings.

PMID- 29071331
TI  - Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following
      Acute Coronary Syndrome: Analysis of the dal-Outcomes Randomized Clinical Trial.
AB  - Importance: It is uncertain whether lipoprotein(a) [Lp(a)], which is associated
      with incident cardiovascular disease, is an independent risk factor for recurrent
      cardiovascular events after acute coronary syndrome (ACS). Objective: To
      determine the association of Lp(a) concentration measured after ACS with the
      subsequent risk of ischemic cardiovascular events. Design, Setting, and
      Participants: This nested case-cohort analysis was performed as an ad hoc
      analysis of the dal-Outcomes randomized clinical trial. This trial compared
      dalcetrapib, the cholesteryl ester transfer protein inhibitor, with placebo in
      patients with recent ACS and was performed between April 2008 and September 2012
      at 935 sites in 27 countries. There were 969 case patients who experienced a
      primary cardiovascular outcome, and there were 3170 control patients who were
      event free at the time of a case event and had the same type of index ACS
      (unstable angina or myocardial infarction) as that of the respective case
      patients. Concentration of Lp(a) was measured by immunoturbidimetric assay. Data
      analysis for this present study was conducted from June 8, 2016, to April 21,
      2017. Interventions: Patients were randomly assigned to receive treatment with
      dalcetrapib, 600 mg daily, or matching placebo, beginning 4 to 12 weeks after
      ACS. Main Outcomes and Measures: Death due to coronary heart disease, a major
      nonfatal coronary event (myocardial infarction, hospitalization for unstable
      angina, or resuscitated cardiac arrest), or fatal or nonfatal ischemic stroke.
      Results: The mean (SD) age was 63 (10) years for the 969 case patients and 60 (9)
      years for the 3170 control patients, and both cohorts were composed of
      predominantly male (770 case patients [79%] and 2558 control patients [81%]; P =
      .40) and white patients (858 case patients [89%] and 2825 control patients [89%];
      P = .62). At baseline, the median (interquartile range) Lp(a) level was 12.3 (4.7
      50.9) mg/dL. There was broad application of evidence-based secondary prevention
      strategies after ACS, including use of statins in 4030 patients (97%). The
      cumulative distribution of baseline Lp(a) levels did not differ between cases and
      controls at P = .16. Case-cohort regression analysis showed no association of
      baseline Lp(a) level with risk of cardiovascular events. For a doubling of Lp(a)
      concentration, the hazard ratio (case to control) was 1.01 (95% CI, 0.96-1.06; P
      = .66) after adjustment for 16 baseline variables, including assigned study
      treatment. Conclusions and Relevance: For patients with recent ACS who are
      treated with statins, Lp(a) concentration was not associated with adverse
      cardiovascular outcomes. These findings call into question whether treatment
      specifically targeted to reduce Lp(a) levels would thereby lower the risk for
      ischemic cardiovascular events after ACS. Trial Registration: clinicaltrials.gov
      Identifier: NCT00658515.

PMID- 29071332
TI  - Effect of Chewing vs Swallowing Ticagrelor on Platelet Inhibition in Patients
      With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.
AB  - Importance: Dual anti-platelet therapy represents standard care for treating
      patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a
      direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not
      require metabolic activation. Objective: To evaluate whether chewing a loading
      dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal
      dose enhances platelet inhibition at 30 minutes and 1 hour after LD
      administration in patients with STEMI. Design, Setting, and Participants: A
      randomized clinical trial was conducted in adults aged 30 to 87 years from May to
      October 2016 in a large tertiary care center. Analyses were intention-to-treat.
      Interventions: Fifty patients with STEMI were randomized to either chewing an LD
      of ticagrelor, 180 mg, or standard oral administration of an equal dose. Main
      Outcomes and Measures: P2Y12 reaction units were evaluated using VerifyNow
      (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. Results:
      Baseline characteristics were similar in both groups. The mean (SD) of P2Y12
      reaction units in the chewing group compared with the standard group at baseline,
      30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44)
      (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to 
      19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and
      43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet
      reactivity in the chewing group was significantly reduced by 24% at 30 minutes
      after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet
      aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69
      to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24)
      at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at
      30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to
      16.93; P > .99). Conclusions and Relevance: Chewing an LD of ticagrelor, 180 mg,
      in patients with STEMI is feasible and facilitates better early platelet
      inhibition compared with a standard oral LD. Larger studies are warranted to see
      if our preliminary findings translate into clinical outcomes. Trial Registration:
      clinicaltrials.gov Identifier: NCT02725099.

PMID- 29071327
TI  - Engineering of inorganic nanoparticles as magnetic resonance imaging contrast
      agents.
AB  - Magnetic resonance imaging (MRI) is a highly valuable non-invasive imaging tool
      owing to its exquisite soft tissue contrast, high spatial resolution, lack of
      ionizing radiation, and wide clinical applicability. Contrast agents (CAs) can be
      used to further enhance the sensitivity of MRI to obtain information-rich images.
      Recently, extensive research efforts have been focused on the design and
      synthesis of high-performance inorganic nanoparticle-based CAs to improve the
      quality and specificity of MRI. Herein, the basic rules, including the choice of
      metal ions, effect of electron motion on water relaxation, and involved
      mechanisms, of CAs for MRI have been elucidated in detail. In particular, various
      design principles, including size control, surface modification (e.g. organic
      ligand, silica shell, and inorganic nanolayers), and shape regulation, to impact
      relaxation of water molecules have been discussed in detail. Comprehensive
      understanding of how these factors work can guide the engineering of future
      inorganic nanoparticles with high relaxivity. Finally, we have summarized the
      currently available strategies and their mechanism for obtaining high-performance
      CAs and discussed the challenges and future developments of nanoparticulate CAs
      for clinical translation in MRI.

PMID- 29071334
TI  - Association Between Appendectomy Outcomes and Surgeons' Seniority.

PMID- 29071333
TI  - Association of Anti-Factor Xa-Guided Dosing of Enoxaparin With Venous
      Thromboembolism After Trauma.
AB  - Importance: The efficacy of anti-factor Xa (anti-Xa)-guided dosing of
      thromboprophylaxis after trauma remains controversial. Objective: To assess
      whether dosing of enoxaparin sodium based on peak anti-Xa levels is associated
      with the venous thromboembolism (VTE) rate after trauma. Design, Setting, and
      Participants: Retrospective review of 950 consecutive adults admitted to a single
      level I trauma intensive care unit for more than 48 hours from December 1, 2014,
      through March 31, 2017. Within 24 hours of admission, these trauma patients were
      screened with the Greenfield Risk Assessment Profile (RAP) (possible score range,
      0-46). Patients younger than 18 years and those with VTE on admission were
      excluded, resulting in a study population of 792 patients. Exposures: The control
      group received fixed doses of either heparin sodium, 5000 U 3 times a day, or
      enoxaparin sodium, 30 mg twice a day. The adjustment cohort initially received
      enoxaparin sodium, 30 mg twice a day. A peak anti-Xa level was drawn 4 hours
      after the third dose. If the anti-Xa level was 0.2 IU/mL or higher, no adjustment
      was made. If the anti-Xa level was less than 0.2 IU/mL, each dose was increased
      by 10 mg. The process was repeated up to a maximum dose of 60 mg twice a day.
      Main Outcomes and Measures: Rates of VTE were measured. Venous duplex
      ultrasonography and computed tomographic angiography were used for diagnosis.
      Results: The study population comprised 792 patients with a mean (SD) age of 46
      (19) years and was composed of 598 men (75.5%). The control group comprised 570
      patients, was older, and had a longer time to thromboprophylaxis initiation. The
      adjustment group consisted of 222 patients, was more severely injured, and had a
      longer hospital length of stay. The mean (SD) RAP scores were 9 (4) for the
      control group and 9 (5) for the adjustment group (P = .28). The VTE rates were
      similar for both groups (34 patients [6.0%] vs 15 [6.8%]; P = .68). Prophylactic
      anti-Xa levels were reached in 119 patients (53.6%) in the adjustment group. No
      difference in VTE rates was observed between those who became prophylactic and
      those who did not (7 patients [5.9%] vs 8 [7.8%]; P = .58). To control for
      confounders, 132 patients receiving standard fixed-dose enoxaparin were
      propensity matched to 84 patients receiving dose-adjusted enoxaparin. The VTE
      rates remained similar between the control and adjustment groups (3 patients
      [2.3%] vs 3 [3.6%]; P = .57). Conclusions and Relevance: Rates of VTE were not
      reduced with anti-Xa-guided dosing, and almost half of the patients never reached
      prophylactic anti-Xa levels; achieving those levels did not decrease VTE rates.
      Thus, other targets, such as platelets, may be necessary to optimize
      thromboprophylaxis after trauma.

PMID- 29071336
TI  - Interdisciplinary Disease-Based Peer Review: Moving Quality Assurance Into the
      Future.

PMID- 29071337
TI  - Evaluation of Military Use of Tranexamic Acid and Associated Thromboembolic
      Events.
AB  - Importance: Since publication of the CRASH-2 and MATTERs studies, the US military
      has included tranexamic acid (TXA) in clinical practice guidelines. While TXA was
      shown to decrease mortality in trauma patients requiring massive transfusion,
      improper administration and increased risk of venous thromboembolism remain a
      concern. Objective: To determine the appropriateness of TXA administration by US
      military medical personnel based on current Joint Trauma System clinical practice
      guidelines and to determine if TXA administration is associated with venous
      thromboembolism. Design, Setting, and Participants: This cohort study of US
      military casualties in US military combat support hospitals in Afghanistan and a
      single US-based tertiary military treatment facility within the continental
      United States was conducted from 2011 to 2015, with follow-up through initial
      hospitalization and readmissions. Exposures: Data collected for all patients
      included demographic information as well as Injury Severity Score; receipt of
      blood products, TXA, and/or a massive transfusion; and admission hemodynamics.
      Main Outcomes and Measures: Variance from guidelines in TXA administration and
      venous thromboembolism. Tranexamic acid overuse was defined as a hemodynamically
      stable patient receiving TXA but not a massive transfusion, underuse was defined
      as a patient receiving a massive transfusion but not TXA, and TXA administration
      was considered delayed when given more than 3 hours after injury. Results: Of the
      455 identified patients, 443 (97.4%) were male, and the mean (SD) age was 25.3
      (4.8) years. A total of 173 patients (38.0%) received a massive transfusion, and
      139 (30.5%) received TXA in theater. Overuse occurred in 18 of 282 patients
      (6.4%) and underuse in 46 of 173 (26.6%) receiving massive transfusions, and
      delayed administration was found in 6 of 145 patients (4.3%) receiving TXA.
      Overuse increased at 3.3% per quarter (95% CI, 4.0-9.9; P < .001; R2 = 0.340) and
      underuse decreased at -4.4% per quarter (95% CI, -4.5 to -3.6; P < .001; R2 =
      0.410). Tranexamic acid administration was an independent risk factor for venous
      thromboembolism (odds ratio, 2.58; 95% CI, 1.20-5.56; P = .02). Conclusions and
      Relevance: Military medical personnel decreased missed opportunities to
      appropriately use TXA but also increased overuse. In addition, TXA administration
      was an independent risk factor for venous thromboembolism. A reevaluation of the
      use of TXA in combat casualties should be undertaken.

PMID- 29071335
TI  - Prevalence of Untreated Surgical Conditions in Rural Rwanda: A Population-Based
      Cross-sectional Study in Burera District.
AB  - Importance: In low- and middle-income countries, community-level surgical
      epidemiology is largely undefined. Accurate community-level surgical epidemiology
      is necessary for surgical health systems planning. Objective: To determine the
      prevalence of surgical conditions in Burera District, Northern Province, Rwanda.
      Design, Setting, and Participants: A cross-sectional study with a 2-stage cluster
      sample design (at village and household level) was carried out in Burera District
      in March and May 2012. A team of surgeons randomly sampled 30 villages with
      probability proportionate to village population size, then sampled 23 households
      within each village. All available household members were examined. Main Outcomes
      and Measures: The presence of 10 index surgical conditions (injuries/wounds,
      hernias/hydroceles, breast masses, neck masses, obstetric fistulas, undescended
      testes, hypospadias, hydrocephalus, cleft lip/palate, and clubfoot) was
      determined by physical examination. Prevalence was estimated overall and for each
      condition. Multivariable logistic regression was performed to identify factors
      associated with surgical conditions, accounting for the complex survey design.
      Results: Of the 2165 examined individuals, 1215 (56.2%) were female. The
      prevalence of any surgical condition among all examined individuals was 12% (95%
      CI, 9.2-14.9%). Half of conditions were hernias/hydroceles (49.6%), and 44% were
      injuries/wounds. In multivariable analysis, children 5 years or younger had twice
      the odds of having a surgical condition compared with married individuals 21 to
      35 years of age (reference group) (odds ratio [OR], 2.2; 95% CI, 1.26-4.04; P =
      .01). The oldest group, people older than 50 years, also had twice the odds of
      having a surgical condition compared with the reference group (married, aged >50
      years: OR, 2.3; 95% CI, 1.28-4.23; P = .01; unmarried, aged >50 years: OR, 2.38;
      95% CI, 1.02-5.52; P = .06). Unmarried individuals 21 to 35 years of age and
      unmarried individuals aged 36 to 50 years had higher odds of a surgical condition
      compared with the reference group (aged 21-35 years: OR, 1.68; 95% CI, 0.74-3.82;
      P = .22; aged 36-50 years: OR, 3.35; 95% CI, 1.29-9.11; P = .02). There was no
      statistical difference in odds by sex, wealth, education, or travel time to the
      nearest hospital. Conclusions and Relevance: The prevalence of surgically
      treatable conditions in northern Rwanda was considerably higher than previously
      estimated modeling and surveys in comparable low- and middle-income countries.
      This surgical backlog must be addressed in health system plans to increase
      surgical infrastructure and workforce in rural Africa.

PMID- 29071339
TI  - Phage Therapy's Role in Combating Antibiotic-Resistant Pathogens.

PMID- 29071338
TI  - Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary
      Hypertension.
AB  - Importance: Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial
      pressure (mPAP) value of at least 25 mm Hg during right heart catheterization
      (RHC). While several studies have demonstrated increased mortality in patients
      with mPAP less than that threshold, little is known about the natural history of
      borderline PH. Objective: To test the hypothesis that patients with borderline PH
      have decreased survival compared with patients with lower mPAP and frequently
      develop overt PH and to identify clinical correlates of borderline PH. Design,
      Setting, and Participants: Retrospective cohort study from 1998 to 2014 at
      Vanderbilt University Medical Center, comprising all patients undergoing routine
      RHC for clinical indication. We extracted demographics, clinical data, invasive
      hemodynamics, echocardiography, and vital status for all patients. Patients with
      mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were
      classified as reference, borderline PH, and PH, respectively. Exposures: Mean
      pulmonary arterial pressure. Main Outcome and Measures: Our primary outcome was
      all-cause mortality after adjusting for clinically relevant covariates in a Cox
      proportional hazards model. Our secondary outcome was the diagnosis of overt PH
      in patients initially diagnosed with borderline PH. Both outcomes were determined
      prior to data analysis. Results: We identified 4343 patients (mean [SD] age, 59
      [15] years, 51% women, and 86% white) among whom the prevalence of PH and
      borderline PH was 62% and 18%, respectively. Advanced age, features of the
      metabolic syndrome, and chronic heart and lung disease were independently
      associated with a higher likelihood of borderline PH compared with reference
      patients in a logistic regression model. After adjusting for 34 covariates in a
      Cox proportional hazards model, borderline PH was associated with increased
      mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04
      1.65; P = .001). The hazard of death increased incrementally with higher mPAP,
      without an observed threshold. In the 70 patients with borderline PH who
      underwent a repeated RHC, 43 (61%) had developed overt PH, with a median increase
      in mPAP of 5 mm Hg (interquartile range, -1 to 11 mm Hg; P < .001). Conclusions
      and Relevance: Borderline PH is common in patients undergoing RHC and is
      associated with significant comorbidities, progression to overt PH, and decreased
      survival. Small increases in mPAP, even at values currently considered normal,
      are independently associated with increased mortality. Prospective studies are
      warranted to determine whether early intervention or closer monitoring improves
      clinical outcomes in these patients.

PMID- 29071340
TI  - Combined Effects of Noise and Reverberation on Sound Localization for Listeners
      With Normal Hearing and Bilateral Cochlear Implants.
AB  - Purpose: This study examined the individual and combined effects of noise and
      reverberation on the ability of listeners with normal hearing (NH) and with
      bilateral cochlear implants (BCIs) to localize speech. Method: Six adults with
      BCIs and 10 with NH participated. All subjects completed a virtual localization
      test in quiet and at 0-, -4-, and -8-dB signal-to-noise ratios (SNRs) in
      simulated anechoic and reverberant (0.2-, 0.6-, and 0.9-s RT60) environments. BCI
      users were also tested at +8- and +4-dB SNR. A 3-word phrase was presented at 70
      dB SPL from 9 simulated locations in the frontal horizontal plane (+/-90 degrees
      ), with the noise source at 0 degrees . Results: BCIs users had significantly
      poorer localization than listeners with NH in all conditions. BCI users'
      performance started to decrease at a higher SNR (+4 dB) and shorter RT60 (0.2 s)
      than listeners with NH (-4 dB and 0.6 s). The combination of noise and
      reverberation began to degrade localization of BCI users at a higher SNR and a
      shorter RT60 than listeners with NH. Conclusion: The clear effect of noise and
      reverberation on the performance of BCI users provides information that should be
      useful for refining cochlear implant processing strategies and developing
      cochlear implant rehabilitation plans to optimize binaural benefit for BCI users
      in everyday listening situations.

PMID- 29071341
TI  - An Annular Eruption on the Trunk and Limbs.

PMID- 29071343
TI  - Error in Results.

PMID- 29071342
TI  - Pass-Through of a Tax on Sugar-Sweetened Beverages at the Philadelphia
      International Airport.

PMID- 29071345
TI  - Clinical and Serologic Evolution of Multiple Penile Chancres in a Man Who Has Sex
      With Men.

PMID- 29071346
TI  - Challenges in the Study of Genetic Variants of Comorbid Alcohol Use Disorder and
      Major Depression.

PMID- 29071344
TI  - Genetic Risk Variants Associated With Comorbid Alcohol Dependence and Major
      Depression.
AB  - Importance: Alcohol dependence (AD) and major depression (MD) are leading causes
      of disability that often co-occur. Genetic epidemiologic data have shown that AD
      and MD share a common possible genetic cause. The molecular nature of this shared
      genetic basis is poorly understood. Objectives: To detect genetic risk variants
      for comorbid AD and MD and to determine whether polygenic risk alleles are shared
      with neuropsychiatric traits or subcortical brain volumes. Design, Setting, and
      Participants: This genome-wide association study analyzed criterion counts of
      comorbid AD and MD in African American and European American data sets collected
      as part of the Yale-Penn study of the genetics of drug and alcohol dependence
      from February 14, 1999, to January 13, 2015. After excluding participants never
      exposed to alcohol or with missing information for any diagnostic criterion,
      genome-wide association studies were performed on 2 samples (the Yale-Penn 1 and
      Yale-Penn 2 samples) totaling 4653 African American participants and 3169
      European American participants (analyzed separately). Tests were performed to
      determine whether polygenic risk scores derived from potentially related traits
      in European American participants could be used to estimate comorbid AD and MD.
      Main Outcomes and Measures: Comorbid criterion counts (ranging from 0 to 14) for
      AD (7 criteria) and MD (9 criteria, scaled to 7) as defined by the DSM-IV.
      Results: Of the 7822 participants (3342 women and 4480 men; mean [SD] age, 40.1
      [10.7] years), the median comorbid criterion count was 6.2 (interquartile range,
      2.3-10.9). Under the linear regression model, rs139438618 at the semaphorin 3A
      (SEMA3A [OMIM 603961]) locus was significantly associated with AD and MD
      comorbidity in African American participants in the Yale-Penn 1 sample (beta =
      0.89; 95% CI, 0.57-1.20; P = 2.76 * 10-8). In the independent Yale-Penn 2 sample,
      the association was also significant (beta = 0.83; 95% CI, 0.39-1.28; P = 2.06 *
      10-4). Meta-analysis of the 2 samples yielded a more robust association (beta =
      0.87; 95% CI, 0.61-1.12; P = 2.41 * 10-11). There was no significant association
      identified in European American participants. Analyses of polygenic risk scores
      showed that individuals with a higher risk of neuroticism (beta = 1.01; 95% CI,
      0.50-1.52) or depressive symptoms (beta = 0.87; 95% CI, 0.32-1.42) and a lower
      level of subjective well-being (beta = -0.94; 95% CI, -1.46 to -0.42) and
      educational attainment (beta = -1.00, 95% CI, -1.57 to -0.44) had a higher level
      of AD and MD comorbidity, while larger intracranial (beta = 1.07; 95% CI, 0.50 to
      1.64) and smaller putamen volumes (beta = -1.16; 95% CI, -1.86 to -0.46) were
      associated with higher risks of AD and MD comorbidity. Conclusions and Relevance:
      SEMA3A variation is significantly and replicably associated with comorbid AD and
      MD in African American participants. Analyses of polygenic risk scores identified
      pleiotropy with neuropsychiatric traits and brain volumes. Further studies are
      warranted to understand the biological and genetic mechanisms of this
      comorbidity, which could facilitate development of medications and other
      treatments for comorbid AD and MD.

PMID- 29071348
TI  - CORRECTIONS TO: Reviewers.

PMID- 29071349
TI  - Tanning Salon Compliance Rates in States With Legislation to Protect Youth Access
      to UV Tanning.
AB  - Importance: The US Food and Drug Administration has classified tanning beds as
      carcinogenic. Most states have enacted legislation to prevent or create barriers
      for minors accessing tanning establishments. Determining tanning salon compliance
      with legislation would provide an indication of the influence of legislation at
      preventing exposure to the carcinogen in minors. Objectives: To investigate
      compliance rates in the 42 states and the District of Columbia with legislation
      restricting tanning bed use in minors and to identify differences in compliance
      based on population, regional location, salon ownership, age group being
      regulated, and time since the law was enacted. Design, Setting, and Participants:
      This investigation was a cross-sectional telephone survey conducted between
      February 1, 2015, and April 30, 2016, by callers posing as minors attempting to
      schedule a tanning appointment. The setting was tanning salons in the 42 states
      and the District of Columbia that currently have legislation restricting tanning
      bed use in minors. Included in the study were 427 tanning salons, 10 randomly
      selected from each state or territory with tanning legislation. Main Outcomes and
      Measures: Overall compliance of tanning salons with state tanning legislation and
      differences in compliance based on community population, regional location,
      independent vs chain tanning salon, age group being regulated, and time since the
      law was enacted. Results: Of the 427 tanning salons surveyed, overall
      noncompliance with state legislation was 37.2% (n = 159). There were more
      noncompliant tanning salons in rural locations (45.5%; 95% CI, 37.5%-53.7%; P =
      .009), southern regions of the United States (49.4%; 95% CI, 41.4%-57.4%; P =
      .001), independently owned salons (43.9%; 95% CI, 37.3%-50.6%; P = .003), states
      with younger age groups being regulated (53.5%; 95% CI, 45.7%-61.2%; P < .001),
      and states with more than one tanning regulation (50.0%; 95% CI, 42.0%-58.0%; P <
      .001). No difference was found based on time since the law was enacted.
      Conclusions and Relevance: Compliance with state legislation aimed at limiting
      tanning bed use among US minors is unsatisfactory, indicating that additional
      efforts to enforce the laws and education of the harmful effects of UV tanning
      are necessary, especially in rural, independently owned, and tanning salons in
      southern regions, which have decreased compliance rates.

PMID- 29071347
TI  - Sun Protection Policies in Public School Districts With Elementary Schools in
      California.

PMID- 29071350
TI  - Does Tranexamic Acid Cause Venous Thromboembolism After Trauma?: Who Cares, If It
      Saves Lives?

PMID- 29071351
TI  - Image-based and eye-based influences on binocular rivalry have similar spatial
      profiles.
AB  - Binocular rivalry occurs when the images presented to the two eyes do not match.
      Instead of fusing into a stable percept, perception during rivalry alternates
      between images over time. However, during rivalry, perception can also resemble a
      patchwork of parts of both eyes' images. Such integration of image parts across
      eyes is relatively rare compared to integration of image parts presented to the
      same eye, suggesting that integration across space during rivalry is primarily
      rooted at the early monocular level of processing. However, recent evidence
      suggests that rivalry, and potentially also integration across space during
      rivalry, has its basis at multiple stages of processing, including stages at
      which monocular signals are minimal. As such, integration and competition at
      these later stages would be driven more by image-based factors, such as
      continuity and color than by eye of origin. Because "higher" visual areas also
      have increasingly larger receptive fields, image-based integration may occur over
      a larger spatial extent compared to monocular, eye-based integration. We
      therefore used rival images containing two separate image parts and varied the
      interimage-part distance (IIPD) to assess the relative contributions of eye of
      origin and image features to integration across space at increasing IIPDs. Our
      hypothesis was that the balance between these contributions would shift toward
      image features as IIPD increased. Instead, results show that the relative
      contributions of both factors to grouping remain constant as a function of IIPD.
      This indicates that image-based grouping is subject to similar spatial
      constraints as monocular, eye-based grouping, suggesting both kinds of grouping
      rely on similarly sized receptive fields.

PMID- 29071352
TI  - Characterizing eye movement behaviors and kinematics of non-human primates during
      virtual navigation tasks.
AB  - Virtual environments (VE) allow testing complex behaviors in naturalistic
      settings by combining highly controlled visual stimuli with spatial navigation
      and other cognitive tasks. They also allow for the recording of eye movements
      using high-precision eye tracking techniques, which is important in
      electrophysiological studies examining the response properties of neurons in
      visual areas of nonhuman primates. However, during virtual navigation, the
      pattern of retinal stimulation can be highly dynamic which may influence eye
      movements. Here we examine whether and how eye movement patterns change as a
      function of dynamic visual stimulation during virtual navigation tasks, relative
      to standard oculomotor tasks. We trained two rhesus macaques to use a joystick to
      navigate in a VE to complete two tasks. To contrast VE behavior with classic
      measurements, the monkeys also performed a simple Cued Saccade task. We used a
      robust algorithm for rapid classification of saccades, fixations, and smooth
      pursuits. We then analyzed the kinematics of saccades during all tasks, and
      specifically during different phases of the VE tasks. We found that fixation to
      smooth pursuit ratios were smaller in VE tasks (4:5) compared to the Cued Saccade
      task (7:1), reflecting a more intensive use of smooth pursuit to foveate targets
      in VE than in a standard visually guided saccade task or during spontaneous
      fixations. Saccades made to rewarded targets (exploitation) tended to have
      increased peak velocities compared to saccades made to unrewarded objects
      (exploration). VE exploitation saccades were 6% slower than saccades to discrete
      targets in the Cued Saccade task. Virtual environments represent a technological
      advance in experimental design for nonhuman primates. Here we provide a framework
      to study the ways that eye movements change between and within static and dynamic
      displays.

PMID- 29071354
TI  - A relative frame of reference underlies reversed depth perception in
      anticorrelated random-dot stereograms.
AB  - Binocular disparity is represented by interocular cross-correlation of visual
      images in the striate and some extrastriate cortices. This correlation-based
      representation produces reversed depth perception in a binocularly anticorrelated
      random-dot stereogram (aRDS) when it is accompanied by an adjacent correlated RDS
      (cRDS). Removal of the cRDS or spatial separation between the aRDS and cRDS
      abolishes reversed depth perception. However, how an immediate plane supports
      reversed depth perception is unclear. One possible explanation is that the
      correlation-based representation generates reversed depth based on the relative
      disparity between the aRDS and cRDS rather than the absolute disparity of the
      aRDS. Here, we psychophysically tested this hypothesis. We found that
      participants perceived reversed depth in an aRDS with zero absolute disparity
      when it was surrounded by a cRDS with nonzero absolute disparity (i.e., nonzero
      relative disparity), suggesting a role of relative disparity on the depth
      reversal. In addition, manipulation of the absolute disparities of the central
      aRDS and surrounding cRDS caused depth perception to reverse with respect to the
      depth of the surround. Further, depth reversal persisted after swapping the
      locations of the two RDSs. A model of relative-disparity encoding explains all
      these results. We conclude that reversed depth perception in aRDSs occurs in a
      relative frame of reference and suggest that the visual system contains
      correlation-based representation that encodes relative disparity.

PMID- 29071353
TI  - Linking normative models of natural tasks to descriptive models of neural
      response.
AB  - Understanding how nervous systems exploit task-relevant properties of sensory
      stimuli to perform natural tasks is fundamental to the study of perceptual
      systems. However, there are few formal methods for determining which stimulus
      properties are most useful for a given natural task. As a consequence, it is
      difficult to develop principled models for how to compute task-relevant latent
      variables from natural signals, and it is difficult to evaluate descriptive
      models fit to neural response. Accuracy maximization analysis (AMA) is a recently
      developed Bayesian method for finding the optimal task-specific filters
      (receptive fields). Here, we introduce AMA-Gauss, a new faster form of AMA that
      incorporates the assumption that the class-conditional filter responses are
      Gaussian distributed. Then, we use AMA-Gauss to show that its assumptions are
      justified for two fundamental visual tasks: retinal speed estimation and
      binocular disparity estimation. Next, we show that AMA-Gauss has striking formal
      similarities to popular quadratic models of neural response: the energy model and
      the generalized quadratic model (GQM). Together, these developments deepen our
      understanding of why the energy model of neural response have proven useful,
      improve our ability to evaluate results from subunit model fits to neural data,
      and should help accelerate psychophysics and neuroscience research with natural
      stimuli.

PMID- 29071355
TI  - Extent of Dorsolateral Prefrontal Cortex Plasticity and Its Association With
      Working Memory in Patients With Alzheimer Disease.
AB  - Importance: The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in
      Alzheimer disease (AD) and its association with working memory are not known.
      Objectives: To determine whether participants with AD had impaired DLPFC
      plasticity compared with healthy control participants, to compare working memory
      between participants with AD and controls, and to determine whether DLPFC
      plasticity was associated with working memory. Design, Setting, and Participants:
      This cross-sectional study included 32 participants with AD who were 65 years or
      older and met diagnostic criteria for dementia due to probable AD with a score of
      at least 17 on the Mini-Mental State Examination and 16 age-matched control
      participants. Participants were recruited from a university teaching hospital
      from May 2013 to October 2016. Main Outcomes and Measures: Plasticity of the
      DLPFC measured as potentiation of cortical-evoked activity using paired
      associative stimulation (a combination of peripheral nerve electrical stimulation
      and transcranial magnetic stimulation) combined with electroencephalography.
      Working memory was assessed with the n-back task (1- and 2-back) and measured
      using the A' statistic. Results: Among the 32 participants with AD, 17 were women
      and 15 were men (mean [SD] age, 76.3 [6.3] years); among the 16 controls, 8 were
      men and 8 were women (mean [SD] age, 76.4 [5.1] years). Participants with AD had
      impaired DLPFC plasticity (mean [SD] potentiation, 1.18 [0.25]) compared with
      controls (mean [SD] potentiation, 1.40 [0.35]; F1,44 = 5.90; P = .02; between
      group comparison, Cohen d = 0.77; P = .01). Participants with AD also had
      impaired performances on the 1-back condition (mean [SD] A' = 0.47 [0.30])
      compared with controls (mean [SD] A' = 0.96 [0.01]; Cohen d = 1.86; P < .001),
      with similar findings for participants with AD on the 2-back condition (mean [SD]
      A' = 0.29 [0.2]) compared with controls (mean [SD], A' = 0.85 [0.18]; Cohen d =
      2.83; P < .001). Plasticity of DLPFC was positively associated with working
      memory performance on the 1-back A' (parameter estimate B [SE] = 0.32 [0.13];
      standardized beta = 0.29; P = .02) and 2-back A' (B [SE] = 0.43 [0.15]; beta =
      0.39; P = .006) across both groups after controlling for age, education, and
      attention. Conclusions and Relevance: This study demonstrated impaired in vivo
      DLPFC plasticity in patients with AD. The findings support the use of DLPFC
      plasticity as a measure of DLPFC function and a potential treatment target to
      enhance DLPFC function and working memory in patients with AD.

PMID- 29071356
TI  - No improvement in reducing outliers in coronal axis alignment with patient
      specific instrumentation.
AB  - PURPOSE AND HYPOTHESIS: Patient-specific instrumentation (PSI) uses 3D
      preoperative imaging to produce individualized cutting blocks specific to
      patients' anatomy and according to the preoperative plan with the aim to reduce
      the number of mechanical leg alignment (MLA) outliers, to improve implant
      positioning and to decrease surgery time. The primary purpose of this study was
      to investigate the efficacy of a specific PSI in comparison with standard
      instrumentation (SI) in reducing the number of MLA outliers. It was hypothesized
      that the number of MLA outliers would be significantly lower in the PSI group.
      METHODS: A multicenter randomized controlled trial was implemented. There were 59
      patients in the PSI group and 66 in the SI group. The absolute number of outliers
      outside the +/- 3 degrees  target neutral MLA was compared between the groups
      with a Chi-square test. As secondary outcomes, the Knee Society Score (KSS) and
      the Knee Injury and Osteoarthritis Outcome Score (KOOS) were compared between the
      groups preoperatively and at 90-day follow-up. RESULTS: There were 15 (26.3%) MLA
      outliers in the PSI group and 8 (12.3%) in the SI group. The number of outliers
      was not independent from the group ( X2 (1) = 3.8, p = 0.04; Relative risk =
      1.5). Preoperatively, there were no significant differences between the groups
      when comparing their KSS and KOOS sub-scores. At 90 days postoperatively, the
      patients in the SI group showed better KOOS-Quality of Life (KOSS-QOL) in
      comparison with the PSI group (p < 0.0001). CONCLUSION: The use of PSI did not
      significantly reduce the number of MLA outliers in comparison with SI. There were
      no differences when comparing the achieved mean MLA of both groups. LEVEL OF
      EVIDENCE: Level I, prospective randomized controlled trial.

PMID- 29071357
TI  - Evolutionary Analysis of Pectin Lyases of the Genus Colletotrichum.
AB  - Pectin lyases (PNLs) are important enzymes that are involved in plant cell wall
      degradation during the infection process. Colletotrichum is a diverse genus of
      fungi, which allows the study of the evolution of PNLs and their possible role in
      pathogen-host interactions and lifestyle adaptations. The phylogenetic
      reconstruction of PNLs from Colletotrichum and analysis of selection pressures
      showed the formation of protein lineages by groups of species with different
      selection pressures and specific patterns. The analysis of positive selection at
      individual sites using different methods allowed for the identification of three
      codons with evidence of positive selection in the oligosaccharide-binding region
      and two codons on the antiparallel sheet, which may influence the interaction
      with the substrate. Seven codons on the surface of the protein, mainly in the
      peripheral helices of the PNLs, could have an important function in evasion of
      plant defenses, as has been proposed in other enzymes. According to our results,
      it is possible that events of genetic duplication occurred in ancestral lines,
      followed by episodes of genetic diversification and gene loss, probably
      influenced by differences in the composition of the host cell wall. Additionally,
      different patterns of evolution in Colletotrichum appear to be molded by a strong
      purifying selection and positive selection episodes that forged the observed
      evolutionary patterns, possibly influenced by host interaction or substrate
      specificity. This work represents a starting point for the study of sites that
      may be important for evasion of plant defenses and biotechnological purposes.

PMID- 29071359
TI  - Bone marrow failure and extramedullary hematopoiesis in McCune-Albright syndrome.
AB  - In fibrous dysplasia/McCune-Albright syndrome (FD/MAS), bone and bone marrow are,
      to varying degrees, replaced by fibro-osseous tissue typically devoid of
      hematopoietic marrow. Despite the extensive marrow replacement in severely
      affected patients, bone marrow failure is not commonly associated with FD/MAS. We
      present a 14-year-old girl with FD/MAS, who developed pancytopenia and
      extramedullary hematopoiesis (EMH) with no identified cause, in the setting of
      iatrogenic thyrotoxicosis and hyperparathyroidism. Pancytopenia, requiring
      monthly blood transfusions, persisted despite multiple strategies to correct
      these endocrinopathies. Due to worsening painful splenomegaly, likely as a result
      of sequestration, splenectomy was performed. Following splenectomy, pancytopenia
      resolved and patient has since been transfusion-independent.    We report the
      first detailed case of bone marrow failure and EMH in FD/MAS. The etiology of
      marrow failure is likely multifactorial and related to the loss of marrow reserve
      due to extensive polyostotic FD, exacerbated by iatrogenic thyrotoxicosis and
      hyperparathyroidism. Mini Abstract: A patient with fibrous dysplasia developed
      bone marrow failure and extramedullary hematopoiesis. The etiology likely
      involved loss of hematopoetic marrow space and uncontrolled endocrinopathies.
      Splenectomy was therapeutic.

PMID- 29071360
TI  - Prospective observational study of the impact of vaginal surgery (pelvic organ
      prolapse with or without urinary incontinence) on female sexual function.
AB  - INTRODUCTION AND HYPOTHESIS: There is a difference of opinion in the literature
      as to whether pelvic organ prolapse (POP) is a direct cause of female sexual
      dysfunction (FSD). Sexual function in women is negatively impacted by the
      presence of urinary symptoms. Thus, sexual dysfunction (SD) might be improved,
      unchanged, or worsened by pelvic floor surgery. METHODS: In this study, we
      observed SD and impact of surgical intervention on female sexual function (FSF)
      using a validated Prolapse/Urinary Incontinence Sexual Questionnaire Short Form
      (PISQ-12) in women undergoing surgery for POP with or without urinary
      incontinence. Two hundred women were recruited and followed up at 6 and 12 months
      postoperatively. RESULTS: Sexual function (SF) as measured by the PISQ-12
      improved after surgery irrespective of the nature of surgery or the patient's
      past gynaecology history. Improvement in SF was seen by 6 months (97 patients)
      postsurgery (P < 0.05), after which (at 12 months; 80 patients) no further change
      was observed. Improved SF was associated with better patient satisfaction
      postoperatively. CONCLUSIONS: Sexual function improved in women following surgery
      for POP with or withour urinary incontinence, irrespective of the nature of
      surgery and the patient's past gynecologic history. Results of this study will
      assist when counselling women with POP with or without urinary incontinence
      regarding treatment options.

PMID- 29071358
TI  - Tracing the Evolutionary History of the CAP Superfamily of Proteins Using Amino
      Acid Sequence Homology and Conservation of Splice Sites.
AB  - Proteins of the CAP superfamily play numerous roles in reproduction, innate
      immune responses, cancer biology, and venom toxicology. Here we document the
      breadth of the CAP (Cysteine-RIch Secretory Protein (CRISP), Antigen 5, and
      Pathogenesis-Related) protein superfamily and trace the major events in its
      evolution using amino acid sequence homology and the positions of exon/intron
      borders within their genes. Seldom acknowledged in the literature, we find that
      many of the CAP subfamilies present in mammals, where they were originally
      characterized, have distinct homologues in the invertebrate phyla. Early
      eukaryotic CAP genes contained only one exon inherited from prokaryotic
      predecessors and as evolution progressed an increasing number of introns were
      inserted, reaching 2-5 in the invertebrate world and 5-15 in the vertebrate
      world. Focusing on the CRISP subfamily, we propose that these proteins evolved in
      three major steps: (1) origination of the CAP/PR/SCP domain in bacteria, (2)
      addition of a small Hinge domain to produce the two-domain SCP-like proteins
      found in roundworms and anthropoids, and (3) addition of an Ion Channel
      Regulatory domain, borrowed from invertebrate peptide toxins, to produce full
      length, three-domain CRISP proteins, first seen in insects and later to diversify
      into multiple subtypes in the vertebrate world.

PMID- 29071362
TI  - Sclerostin and energy metabolism during physical activity.

PMID- 29071361
TI  - The speed-curvature power law of movements: a reappraisal.
AB  - Several types of curvilinear movements obey approximately the so called 2/3 power
      law, according to which the angular speed varies proportionally to the 2/3 power
      of the curvature. The origin of the law is debated but it is generally thought to
      depend on physiological mechanisms. However, a recent paper (Marken and Shaffer,
      Exp Brain Res 88:685-690, 2017) claims that this power law is simply a
      statistical artifact, being a mathematical consequence of the way speed and
      curvature are calculated. Here we reject this hypothesis by showing that the
      speed-curvature power law of biological movements is non-trivial. First, we
      confirm that the power exponent varies with the shape of human drawing movements
      and with environmental factors. Second, we report experimental data from
      Drosophila larvae demonstrating that the power law does not depend on how
      curvature is calculated. Third, we prove that the law can be violated by means of
      several mathematical and physical examples. Finally, we discuss biological
      constraints that may underlie speed-curvature power laws discovered in empirical
      studies.

PMID- 29071363
TI  - Inter-laboratory analysis of selected genetically modified plant reference
      materials with digital PCR.
AB  - Digital PCR (dPCR), as a new technology in the field of genetically modified (GM)
      organism (GMO) testing, enables determination of absolute target copy numbers.
      The purpose of our study was to test the transferability of methods designed for
      quantitative PCR (qPCR) to dPCR and to carry out an inter-laboratory comparison
      of the performance of two different dPCR platforms when determining the absolute
      GM copy numbers and GM copy number ratio in reference materials certified for GM
      content in mass fraction. Overall results in terms of measured GM% were within
      acceptable variation limits for both tested dPCR systems. However, the determined
      absolute copy numbers for individual genes or events showed higher variability
      between laboratories in one third of the cases, most possibly due to variability
      in the technical work, droplet size variability, and analysis of the raw data.
      GMO quantification with dPCR and qPCR was comparable. As methods originally
      designed for qPCR performed well in dPCR systems, already validated qPCR assays
      can most generally be used for dPCR technology with the purpose of GMO detection.
      Graphical abstract The output of three different PCR-based platforms was assessed
      in an inter-laboratory comparison.

PMID- 29071364
TI  - Reductive oxyamination: a method for the qualitative and quantitative analysis of
      monosaccharides with a new aminooxy reagent using high-performance liquid
      chromatography with fluorescence detection.
AB  - Derivatization of carbohydrates with aminooxy agents to form oximes can be used
      for qualitative and quantitative analysis of carbohydrates; however, the
      formation of isomeric products limits its application. A new reductive
      oxyamination procedure developed for the analysis of monosaccharides with a novel
      fluorescent O-substituted aminooxy reagent, 4-((aminooxy)methyl)-6-chloro-7
      hydroxycoumarin (AOCC), is reported. In this procedure, monosaccharides undergo
      an oxime formation reaction with AOCC and are then readily reduced with 2
      picoline-borane, followed by analysis with high-performance liquid chromatography
      with fluorescence detection. Good separation of five monosaccharide derivatives
      was achieved within 40 min with acetonitrile-water-tetrahydrofuran as the mobile
      phase. The detection limits were on the order of femtomoles. The linear range was
      0.2-4000 nM, with a good correlation coefficient (R >= 0.9985). Furthermore, the
      method was applied for analysis of real samples, such as bovine milk powder,
      without complicated and tedious sample treatment. This reductive oxyamination
      method circumvents the problem caused by oxime isomers and can be used for the
      highly sensitive and selective analysis of monosaccharides with high accuracy,
      providing an effective and promising method for the analysis of carbonyls with
      aminooxy agents.

PMID- 29071365
TI  - Dispersive multi-walled carbon nanotubes extraction of benzenesulfonamides,
      benzotriazoles, and benzothiazoles from environmental waters followed by
      microwave desorption and HPLC-HESI-MS/MS.
AB  - This work shows a novel analytical method for the simultaneous extraction of
      environmental emerging contaminants as benzenesulfonamides (BSAs), benzotriazoles
      (BTRs), and benzothiazoles (BTs) from water samples. Pristine multi-walled carbon
      nanotubes (MWCNTs), not yet tested for such analytes, are here employed as the
      sorbent phase for dispersive solid-phase extraction (d-SPE) followed by high
      performance liquid chromatography/electrospray ionization tandem mass
      spectrometry (HPLC-HESI-MS/MS). Quantitative sorption is gained by treating 50 mL
      sample with 100 mg MWCNTs (2 g L-1) in 10 min contact, both in tap and raw river
      water. After sorption, the analytes are quantitatively desorbed by microwaves (20
      min, 160  degrees C, 250 W) by using 5 mL methanol-ethylacetate-acetic acid
      (10:70:20, v/v), according to the indications obtained by a chemometric study.
      The extract is reduced to small volume before analysis, thus reaching overall
      enrichment factors up to 400. Recovery of the entire procedure, evaluated on tap
      and surface water samples spiked with 0.1/0.5-50 MUg L-1 of each analyte, was in
      the range 70-116%, with excellent inter-day precision (RSD < 7%). Selectivity and
      firm analyte identification were assured by MRM detection, and suitable
      sensitivity was obtained for determination of these pollutants in actual matrices
      (experimental MDLs 30-170 ng L-1). The proposed analytical method was applied to
      the analysis of surface water samples, containing concentrations of these
      contaminants ranging from 100 ng L-1 to 2 MUg L-1. Pristine MWCNTs proved to be a
      valid alternative to other commercial sorbents, both in terms of cost and
      sorption capacity. Graphical abstract Determination of benzenesulfonamides,
      benzotriazoles, and benzothiazoles in environmental waters by dispersive multi
      walled carbon nanotube extraction prior HPLC-MS.

PMID- 29071366
TI  - Perioperative chemotherapy vs. neoadjuvant chemoradiation in gastroesophageal
      junction adenocarcinoma : A population-based evaluation of the Munich Cancer
      Registry.
AB  - BACKGROUND: To date, it remains unclear whether locally advanced adenocarcinoma
      of the gastroesophageal junction (AEG) should be treated with neoadjuvant
      chemoradiation (nCRT), analogous to esophageal cancer, or with perioperative
      chemotherapy (pCT), analogous to gastric cancer. The purpose of this study was to
      analyze the data of the Munich Cancer Registry (MCR) and to compare pCT and nCRT
      in AEG patients. PATIENTS AND METHODS: A total of 2,992 AEG patients, treated
      between 1998 and 2014, were included in the study. Baseline and tumor parameters
      as well as overall survival (OS) and tumor recurrence were compared between 56
      patients undergoing nCRT and 64 patients undergoing pCT with UICC stage II/III
      cancer. In addition, uni- and multivariate analyses using Cox regression models
      were performed to evaluate the effect of tumor characteristics and treatment
      regimens on OS. RESULTS: In patients with UICC stage II/III AEG treated with
      either nCRT or pCT, no significant differences were seen for baseline and tumor
      characteristics. While there was a significantly higher cumulative incidence of
      locoregional treatment failure after pCT (32.8%; 95% CI: 18.0-48.4%) compared
      with nCRT (7.4%; 95% CI: 2.3-16.5%; p = 0.007), there was no significant
      difference for distant treatment failure (52.9%; 95% CI: 35.4-67.7% and 38.4%;
      95% CI: 23.7-52.9%; p = 0.347). When analyzing the whole cohort, patients who
      received pCT were younger (58.3 years vs. 63.0 years; p = 0.016), had a higher
      chance of complete tumor resection (81% vs. 67%; p = 0.033), more resected lymph
      nodes (p = 0.036), and fewer lymph node metastases (p = 0.038) compared with
      patients who received nCRT. Nevertheless, there was still a strong trend toward a
      higher incidence of local treatment failure after pCT (25.8%; 95% CI: 14.7-38.3%
      vs. 12.6%; 95% CI: 5.5-22.8%; p = 0.053). Comparable to the results for patients
      with UICC stage II/III, no difference was seen for the incidence of distant
      treatment failure. When excluding patients with UICC stage IV cancer, no
      significant difference was found for OS. CONCLUSION: For UICC stage II/III
      carcinoma, nCRT was associated with an improved locoregional tumor control
      compared with pCT, while no further significant differences were seen between
      nCRT and pCT for UICC stage II/III AEG. Moreover, there was a strong trend toward
      improved locoregional tumor control after nCRT when analyzing all patients
      treated with nCRT or pCT, despite these patients having higher risk factors.

PMID- 29071367
TI  - Age-Related Patterns in Trace Element Content Vary Between Bone and Teeth of the
      European Roe Deer (Capreolus capreolus).
AB  - Game animals, such as the roe deer (Capreolus capreolus), have long been used as
      bioindicators of environmental contamination. Most ecotoxicological research on
      ungulates has focused on trace element content in soft tissues and antlers. Also,
      only fragmentary information exists about whether and how trace element
      concentrations vary with the age of wild-living animals and whether these age
      related patterns are similar for different types of tissues. The purpose of this
      study was to measure concentrations of seven trace metals (barium, copper, iron,
      lead, manganese, strontium, zinc) and fluoride in bone and teeth of roe deer and
      to determine whether significant variation is evident with individual age. For
      this purpose, we collected permanent molars and fragments of mandible bone from
      more than 130 female roe deer in Central Poland. We found that concentrations of
      four trace elements (barium, manganese, zinc, and fluoride) in teeth of deer
      showed positive linear relationships with individual age. No such trends were
      recorded for trace element content in bone. We suggest that these striking
      differences in age-related patterns of trace element bioaccumulation between bone
      and permanent teeth of roe deer might be explained by higher turnover rate and
      constant remodelling of bone tissue. The results suggest that analysis of
      permanent teeth may be useful for assessing throughout-life intoxication by
      environmental pollution in the roe deer and possibly in other mammal species. Our
      study reinforces the need to carefully account for age-related variation in
      ecotoxicological research on wild-living animals.

PMID- 29071368
TI  - Birds Mediate a Fungus-Mite Mutualism.
AB  - Mutualisms between ophiostomatoid fungi and arthropods have been well documented.
      These fungi commonly aid arthropod nutrition and, in turn, are transported to new
      niches by these arthropods. The inflorescences of Protea trees provide a niche
      for a unique assemblage of ophiostomatoid fungi. Here, mites feed on Sporothrix
      fungi and vector the spores to new niches. Protea-pollinating beetles transport
      the spore-carrying mites between Protea trees. However, many Protea species are
      primarily pollinated by birds that potentially play a central role in the Protea
      Sporothrix-mite system. To investigate the role of birds in the movement of mites
      and/or fungal spores, mites were collected from Protea inflorescences and cape
      sugarbirds, screened for Sporothrix fungal spores and tested for their ability to
      feed and reproduce on the fungal associates. Two mite species where abundant in
      both Protea inflorescences and on cape sugarbirds and regularly carried
      Sporothrix fungal spores. One of these mite species readily fed and reproduced on
      its transported fungal partner. For dispersal, this mite (a Glycyphagus sp.)
      attached to a larger mite species (Proctolaelaps vandenbergi) which, in turn,
      were carried by the birds to new inflorescences. The results of this study
      provide compelling evidence for a new mite-fungus mutualism, new mite-mite
      commensalisms and the first evidence of birds transporting mites with Sporothrix
      fungal spores to colonise new Protea trees.

PMID- 29071369
TI  - Erlang flow of hydrophilic pore formation and closure events in a lipid bilayer
      during phase transition resulting from diffusion in the radius space.
AB  - The Smoluchowski equation with an energy profile of a special type and an assumed
      hydrophobic ("half") pore source term is used to describe the process of
      hydrophilic pore formation in a lipid bilayer at the gel-liquid phase transition.
      The source term reflects the occurrence of molecule packing defects in a lipid
      bilayer at phase transition. The time sequences of the pore formation and closure
      events are treated as non-stationary, second-order Erlang flows whose
      characteristics depend on the equation solution. The computed distributions of
      the time intervals between hydrophilic pores, and pore lifetimes agree with the
      previously published experimental interpulse interval and pulse duration
      histograms for the current fluctuations through planar bilayer membranes of DPPC
      immersed in a LiCl aqueous solution containing polyethylene glycol. Thus, the
      statistical analysis of pore formation and closure times leads us to conclude
      that firstly, the increased permeability of a lipid bilayer during the gel-liquid
      phase transition is accounted for by the emergence of additional hydrophobic
      defects in the heterogeneous structure of the bilayer and secondly, that the non
      exponential distributions of the lipid channel closed and open times observed in
      experiments are evidence that the process of hydrophilic pore formation is not a
      one-step process but involves at least two dependent events.

PMID- 29071371
TI  - On the search of new treatment strategies in patients with affective disorders.

PMID- 29071370
TI  - Determination of the median effective dose (ED50) of bupivacaine and ropivacaine
      unilateral spinal anesthesia : Prospective, double blinded, randomized dose
      response trial.
AB  - BACKGROUND: Unilateral spinal anesthesia (USpA) has been reported to potentiate
      spinal anaesthesia and is used in geriatric patients. The purpose of this study
      was to determine the median effective dose (ED50) of 0.5% hypobaric bupivacaine
      and 0.5% hypobaric ropivacaine USpA for geriatric patients (age >= 70 years)
      undergoing elective hip replacement surgery. METHODS: A total of 60 geriatric
      patients (age >= 70 years) undergoing elective hip replacement surgery were
      enrolled in this study. The patients were randomized into 2 groups to receive
      either intrathecal 0.5% hypobaric bupivacaine USpA (group B) or 0.5% hypobaric
      ropivacaine USpA (group R). Effective anesthesia was defined as a T10 sensory
      blockade level maintained for more than 60 min, and a Bromage score of 3 on the
      operation side within 10 min after injection with no additional epidural
      anesthetic required during surgery. The ED50 of 0.5% hypobaric bupivacaine and
      0.5% hypobaric ropivacaine was calculated using the Dixon and Massey formula.
      RESULTS: No significant differences were found between the two groups in terms of
      demographic data. The ED50 of 0.5% hypobaric bupivacaine USpA was 4.66 mg (95%
      confidence interval CI 4.69-4.63 mg) mg and that of 0.5% hypobaric ropivacaine
      USpA was 6.43 mg (95% CI 6.47-6.39 mg) for geriatric patients undergoing hip
      replacement surgery. CONCLUSION: We find the ED50 were lower, and the ED50 of
      0.5% hypobaric bupivacaine and ropivacaine was 4.66 mg (95% CI 4.69-4.63 mg) and
      6.43 mg (95% CI 6.47-6.39 mg), respectively, for USpA in geriatric patients (age
      >= 70 years) undergoing elective hip replacement surgery.

PMID- 29071372
TI  - Olfactory deficits in individuals at risk for psychosis and patients with
      schizophrenia: relationship with socio-cognitive functions and symptom severity.
AB  - Odor identification deficits are well documented in patients with schizophrenia,
      but it remains unclear whether individuals at clinical high-risk for psychosis
      exhibit similar changes and whether their olfactory function is related to
      social/cognitive functions and symptomatology. In this study, we investigated
      odor detection sensitivity and identification ability in 32 individuals with at
      risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls
      using a T&T olfactometer. The ARMS and schizophrenia subjects were administered
      the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia
      Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning
      Assessment Scale (SOFAS) to assess their cognitive and social functions, and the
      Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS
      and schizophrenia subjects had lower odor identification ability when compared
      with healthy controls, while no significant difference was found in the odor
      detection sensitivity. The lower odor identification ability in the ARMS group
      correlated with the severity of negative symptoms and weakly correlated with
      lower performance on the BACS verbal fluency test. The olfactory measures of
      schizophrenia patients did not correlate with illness duration, medication,
      symptom severity, and social and cognitive functions. For the ARMS and
      schizophrenia groups, the olfactory measures did not correlate with the SOFAS and
      SCoRS scores. These findings suggest that high-risk subjects for psychosis
      already show odor identification deficits similar to those observed in
      schizophrenia patients, which probably reflect a biological trait related to
      vulnerability to psychosis.

PMID- 29071373
TI  - Longitudinal Myocardial Deformation Does Not Predict Single Ventricle Ejection
      Fraction Assessed by Cardiac Magnetic Resonance Imaging in Children with a Total
      Cavopulmonary Connection.
AB  - Survival of children with single ventricle heart defects after the total
      cavopulmonary connection (TCPC) has improved, but impaired cardiac function
      remains a major cause of morbidity and mortality. Cardiac magnetic resonance
      imaging (cMRI) is the gold standard in assessing single ventricle volume and
      function, but high costs and limited availability hamper its routine use. A
      cheaper and more available alternative is echocardiography. Myocardial function
      can be studied in more detail using speckle tracking echocardiography (STE). The
      purpose of the study was to describe the association between myocardial
      deformation assessed by speckle tracking echocardiography (STE) and single
      ventricle function assessed by cMRI and to evaluate differences in myocardial
      deformation in children with single left and single right ventricular morphology.
      Cross-sectional, multicenter study in 77 children after TCPC was conducted. STE
      segmental and global longitudinal peak strain and systolic strain rate (SR) of
      the dominant ventricle were measured. Impaired SV function by cMRI was defined as
      ejection fraction (EF) < 45%. Mean age was 11.8 (range 9.7-14.3) years. Pearson R
      for cMRI EF versus global longitudinal strain and SR was - 0.25 (p = 0.06) and -
      0.03 (p = 0.82), respectively. Global single ventricle longitudinal strain and SR
      was similar in patients after TCPC with single left and single right ventricular
      morphology (- 19.0 +/- 3.1% vs 19.2 +/- 3.2%, p = 0.94). STE myocardial
      deformation parameters do not correlate with single ventricle ejection fraction
      assessed by cMRI.

PMID- 29071375
TI  - [Influence of trauma mechanisms on thoracic and lumbar spinal fractures].
AB  - BACKGROUND: Vertebral body fractures (VBF) can be caused by various trauma
      mechanisms. The AOSpine classification system differentiates three main types of
      fractures according to the grade of instability. How the increasing energy of
      various accident mechanisms changes the complexity of the individual fracture,
      its localization and the occurrence of further fractures has not yet been finally
      investigated. OBJECTIVE: What influence do traumatic events with different
      kinematics have on the localization, complexity and number of VBF in the thoracic
      and lumbar spine? MATERIAL AND METHODS: In this retrospective study data from
      patients with a freshly traumatized VBF were analyzed. The patients were divided
      into six trauma groups (UFG) depending on the trauma mechanism. The VBF were
      classified on the basis of computed tomography (CT) imaging according to the
      AOSpine classification system. Testing was performed bilaterally and a
      significance level of 5% was used. The statistical calculations were carried out
      using IBM SPSS Statistics. RESULTS: A significant increase in the severity of
      fractures (AO classification) was found in the high energy trauma groups (UFG III
      and V). In addition, the incidence of thoracic (TH) VBF was significantly
      increased for TH7 (p = 0.011) and TH10 (p = 0.001). In comparison to the other
      low energy trauma groups, the risk of a TH7 fracture was 7-times higher after a
      high energy trauma (odds ratio OR = 7.0; 95% confidence interval CI = 1.4; 35.2).
      The UFG III (falls > 3 m) showed the highest number of fractures with a median of
      2.5 (SD 1.84) VBF. CONCLUSION: An exact reproduction of the traumatic event
      enables a distinction between high and low energy trauma groups to be made. In
      previous studies traffic accidents were recorded as one group, so an influence of
      the increasing kinematic energy could not be assessed. The accident kinematics
      can be taken into account by differentiating between high and low-energy trauma
      groups. In high-energy accidents the TH7 and TH10 vertebrae were found to be at
      risk vertebrae. In addition to the force direction, the force strength also has a
      decisive influence on the distribution pattern of VBF.

PMID- 29071374
TI  - WAGNER syndrome: anatomic, functional and genetic characterization of a
      Portuguese family.
AB  - PURPOSE: To report the clinical (anatomic and functional) and genetic findings of
      Wagner Syndrome (WS) in a Portuguese family. METHODS: Nine members of the family
      agreed to be examined. All had complete clinical eye examinations. The proband
      and selected patients underwent color fundus photography, spectral domain optical
      coherence tomography (SD-OCT), automatic static white-on-white computerized
      perimetry, and electrophysiology assessment (flash ERG, multifocal(mf) ERG and
      dark adaptometry). A pedigree was constructed based on interviews with known
      affected subjects. Genomic DNA samples derived from venous blood were collected
      from all affected family members examined. RESULTS: Twenty-eight family members
      are affected. This family has the typical features of Wagner Syndrome, namely an
      empty vitreous cavity with veils, mild myopia and cataract. Four examined
      patients underwent vitreoretinal surgery due to abnormal peripheral vitreoretinal
      adhesions with peripheral retinal traction (n = 3). Retinal detachment was
      observed in 5 of the examined subjects. Four of them occurred between the ages of
      5 and 15 years. Chorioretinal atrophy is also a frequent finding which results in
      moderate to severe visual field and advanced rod-cone dystrophy from younger
      ages, also confirmed by absence of scotopic function on dark adaptation. The
      macular dysfunction on mfERG was profound and of early onset. A heterozygous
      mutation in intron 7 of the VCAN gene (c.4004-1G > A) was found. CONCLUSIONS: We
      described a rare autosomal dominant vitreoretinopathy with near complete
      penetrance in a Portuguese family. Abnormal peripheral vitreoretinal adhesions,
      retinal detachment and chorioretinal atrophy are present in most of the examined
      individuals at young ages. Early onset of advanced visual field and
      electrophysiologic abnormalities were observed in this family. We also added
      relevant information to the literature by reporting our experience in surgical
      management of Wagner Syndrome patients with, and at risk of, retinal detachment.

PMID- 29071376
TI  - [Corrective procedures and indications for cavovarus foot deformities in children
      and adolescents].
AB  - Cavovarus deformities in children and adolescents require sound considerations
      concerning the timing for corrective surgery. Progression can be recognized best
      by repeated pedographic examination with evaluation of the typical features of
      cavovarus deformity. Surgical correction consists of a combination of soft tissue
      release, bony realignment, and restoration of muscle balance. In most cases
      plantar or medioplantar soft tissue release should be considered, whereas calf
      muscle lengthening is rarely indicated. Typical joint-sparing bone procedures are
      elevating osteotomies at the medial tarsometatarsal ray and realigning calcaneal
      osteotomies. Advanced cases require navicular-cuneiforme arthrodesis for
      correction of severe cavus component, hindfoot fusion at the Chopart line, or
      Lambrinudi triple fusion. Supramalleolar rotational osteotomy should be
      considered in severe cases. Peroneal dysfunction is addressed by peroneus longus
      to brevis transfer, posterior tibial tendon transfer compensates for severe
      extensor weakness to a certain degree, claw toes can be rebalanced by flexor or
      extensor tendon transfer, often in combination with proximal interphalangeal
      joint fusion. Surgical treatment should take into account the components of
      deformity, muscular function, progression and the underlying disease of the
      individual case. Further deterioration can be prevented by adequate surgery in
      the young patient. However, repeated surgical interventions may be necessary
      later in this patient group.

PMID- 29071377
TI  - [Plate osteosynthesis of patellar fractures].
AB  - OBJECTIVE: Anatomic reconstruction of the retropatellar articular surface and
      repair of the extensor mechanism of the knee joint. The osteosynthesis should
      allow immediate mobilization as part of an early functional postoperative
      rehabilitation protocol. INDICATIONS: Displaced fractures of the patella,
      especially multifragment and comminuted fractures with a retropatellar
      incongruity or dislocation of >2 mm. CONTRAINDICATIONS: Critical local soft
      tissue because of the risk of postoperative infection. SURGICAL TECHNIQUE: Median
      skin incision. For simple (transverse) fractures, preservation of the soft tissue
      and reduction control via the index finger. For complex fractures, lateral
      arthrotomy and eversion of the patella. Reconstruction of the articular surface
      from the joint side with optimal visibility. Temporary fixation with Kirschner
      wires, osteosynthesis with the fixed angle plate. If necessary, additional screws
      or wires. POSTOPERATIVE MANAGEMENT: Immediate mobilization with full
      weightbearing in full extension with a knee brace. Extension/flexion 0/0/60
      degrees  for 4 weeks, then 0/0/90 degrees  until the 7th week. Active extension
      after 6 weeks. Climbing stairs after 12 weeks. RESULTS: Good functional results
      in combination with a low rate of complications and revisions.

PMID- 29071378
TI  - Comparison of PECARN and CATCH clinical decision rules in children with minor
      blunt head trauma.
AB  - INTRODUCTION AND PURPOSE: Computerized brain tomography (CBT) imaging plays a key
      role in the management of patients with head trauma, and there is an indication
      for CBT in moderate and severe injuries. However, it is difficult to determine an
      indication for CBT in patients with minor head trauma. The primary aim of this
      study is to compare the efficiency of the most commonly used clinical decision
      rules: the guidelines of the Pediatric Emergency Care Applied Research Network
      (PECARN), and those of the Canadian Assessment of Tomography for Childhood Head
      Injury (CATCH). METHODS: The study, which was designed as a prospective cohort
      study, sought to determine the appropriate CBT indications for children younger
      than 18 years who were referred to the emergency department with minor blunt head
      trauma. The effectiveness of PECARN and CATCH clinical decision rules, which are
      recommended by literature to be applied in order to diagnose severely injured
      patients and minimize inappropriate CBT requests, was investigated. All patients
      included in this study were younger than 18 years of age, were admitted to the
      study with an isolated blunt head trauma, had a GCS of > 13, and had parental
      permission to participate in the study. Patients ages 18 and older, those with
      penetrating head trauma or trauma to other systems, those with GCS <= 13, those
      with incomplete data, and those whose parents did not agree to participate in the
      study, were excluded. RESULTS: A total of 256 patients were included in the
      study. PECARN and CATCH rules were both shown to be statistically significant in
      detecting the presence of pathology (p < 0.001, p = 0.002, respectively).
      Overall, PECARN was more successful than CATCH in detecting intracranial
      pathology. The sensitivity of PECARN was 95 (95% CI 72-100%) and specificity was
      53 (95% CI 47-60%), while the sensitivity of CATCH was 48 (95% CI 25-71%) and
      specificity was 83 (95% CI 79-88%). Multivariate regression analyses were
      performed on the parameters (low GCS, abnormal mental status, age, non-frontal
      hematoma) and other parameters (vomiting, headache, abnormal behavior according
      to parents) that were considered to be clinically significant despite having a p
      value of < 0.3. Age, low GCS, and non-frontal hematoma presence were found to be
      significant in predicting the presence of pathology. In particular, low GCS
      increased the probability of pathology 5.94-fold and non-frontal hematoma
      presence 4.37-fold. CONCLUSION: While both PECARN and CATCH were found to be
      effective in determining the necessity of CBT for children with minor blunt head
      trauma, PECARN proved to be more useful for emergency services because of its
      higher sensitivity. The authors suggest that conducting a CBT scan based on
      clinical decision rules may be a suitable approach for early detection of the
      presence of intracranial acute pathologies in young children with minor blunt
      head trauma, especially if the GCS score is < 15 and non-frontal hematomas are
      present.

PMID- 29071379
TI  - Cell wall invertase activity regulates the expression of the transfer cell
      specific transcription factor ZmMRP-1.
AB  - MAIN CONCLUSION: Studies in cell wall bound invertase mutants indicate that the
      promoter of the transfer cell-specific transcription factor, ZmMRP - 1 , is
      modulated by the carbohydrate balance. Transfer cells are highly specialized
      plant cells located at the surfaces that need to support an intensive exchange of
      nutrients, such as the entrance of fruits, seeds and nodules or the young
      branching points along the stem. ZmMRP-1 is a one-domain MYB-related
      transcription factor specifically expressed at the transfer cell layer of the
      maize endosperm. Previous studies demonstrated that this factor regulates the
      expression of a large number of transfer cell-specific genes, and suggested that
      ZmMRP-1 is a key regulator of the differentiation of this tissue. The expression
      of this gene is largely dominated by positional cues, but within the ZmMRP-1
      expressing cells the promoter appears to be modulated by sugars. Here we have
      investigated in vivo this modulation. Using maize and Arabidopsis mutants for
      cell wall invertase genes, we found that the absence of cell wall invertase
      activity is a major inductive signal of the ZmMRP-1 expression.

PMID- 29071380
TI  - Satellite cell response to concurrent resistance exercise and high-intensity
      interval training in sedentary, overweight/obese, middle-aged individuals.
AB  - PURPOSE: Sarcopenia can begin from the 4-5th decade of life and is exacerbated by
      obesity and inactivity. A combination of resistance exercise (RE) and endurance
      exercise is recommended to combat rising obesity and inactivity levels. However,
      work continues to elucidate whether interference in adaptive outcomes occur when
      RE and endurance exercise are performed concurrently. This study examined whether
      a single bout of concurrent RE and high-intensity interval training (HIIT) alters
      the satellite cell response following exercise compared to RE alone. METHODS:
      Eight sedentary, overweight/obese, middle-aged individuals performed RE only (8 *
      8 leg extensions at 70% 1RM), or RE + HIIT (10 * 1 min at 90% HRmax on a cycle
      ergometer). Muscle biopsies were collected from the vastus lateralis before and
      96 h after the RE component to determine muscle fiber type-specific total (Pax7+
      cells) and active (MyoD+ cells) satellite cell number using immunofluorescence
      microscopy. RESULTS: Type-I-specific Pax7+ (P = 0.001) cell number increased
      after both exercise trials. Type-I-specific MyoD+ (P = 0.001) cell number
      increased after RE only. However, an elevated baseline value in RE + HIIT
      compared to RE (P = 0.046) was observed, with no differences between exercise
      trials at 96 h (P = 0.21). Type-II-specific Pax7+ and MyoD+ cell number remained
      unchanged after both exercise trials (all P >= 0.13). CONCLUSION: Combining a
      HIIT session after a single bout of RE does not interfere with the increase in
      type-I-specific total, and possibly active, satellite cell number, compared to RE
      only. Concurrent RE + HIIT may offer a time-efficient way to maximise the
      physiological benefits from a single bout of exercise in sedentary,
      overweight/obese, middle-aged individuals.

PMID- 29071381
TI  - Exiting prophase I: no clear boundary.
AB  - The meiotic cell cycle provides a unique model to study the relationship between
      recombinational DNA repair and the cell cycle, since homologous recombination,
      induced by programmed DNA double-strand breaks (DSBs), is integrated as an
      essential step during meiosis. The pachytene checkpoint, which is situated
      towards the end of meiotic prophase I, coordinates homologous recombination and
      cell cycle progression, similar to the DNA damage checkpoint mechanisms operating
      in vegetative cells. However, there are a number of features unique to meiosis,
      making the system optimized for the purpose of meiosis. Our recent work
      highlights the involvement of three major cell cycle kinases, Dbf4-dependent Cdc7
      kinase, Polo kinase and CDK, in coordinating homologous recombination and the
      meiotic cell cycle. In this review, we will discuss the unique interplay between
      meiotic cell cycle control and homologous recombination during meiosis I.

PMID- 29071382
TI  - Hydroxyethyl starch 130/0.4 versus crystalloid co-loading during general
      anesthesia induction: a randomized controlled trial.
AB  - PURPOSE: Hypotension and decreased cardiac output (CO) are common adverse effects
      during anesthesia induction depending on the patient's pre-anesthetic cardiac
      condition. The aim of this study was to assess the ability of hydroxyethyl starch
      (HES) 130/0.4 to prevent hypotension and decreased CO during the induction of
      general anesthesia. METHODS: Ninety patients undergoing laparoscopic surgery were
      randomly divided into a HES group and a crystalloid group. Following the
      insertion of an intravenous line, fluid was administered to each patient at a
      rate of 25 ml/min using either crystalloid or HES 130/0.4. Five minutes after the
      initiation of fluid loading, anesthesia was induced using propofol (1.5 mg/kg),
      rocuronium (0.9 mg/kg), and remifentanil (0.3 mcg/kg/min). Tracheal intubation
      was performed 5 min after the induction of anesthesia. Following tracheal
      intubation, general anesthesia was maintained using remifentanil and sevoflurane.
      Non-invasive blood pressure (BP) level was measured at 1-min intervals and CO was
      measured continuously using electrical cardiometry from the start of fluid
      loading until 5 min after tracheal intubation. RESULTS: The number of patients
      with hypotension (systolic BP < 90 mmHg or 80% of baseline) was significantly
      lower in the HES group (p < 0.001) than in the crystalloid group. Patients in the
      HES group showed smaller CO decreases than did patients in the crystalloid group
      (p < 0.001). The Kaplan-Meier method showed a lower incidence and significantly
      slower onset of hypotension in the HES group (p = 0.009). Multivariate logistic
      regression models indicated that the use of HES is an independent factor for the
      prevention of both hypotension and decreased CO (below 85% of baseline; p < 0.005
      for both). CONCLUSIONS: Co-loading using HES 130/0.4 prevented hypotension and
      decreased CO during general anesthesia induction.

PMID- 29071383
TI  - Involvement of ordinary what and where auditory cortical areas during illusory
      perception.
AB  - The focus of the present study is on the relationships between illusory and non
      illusory auditory perception analyzed at a biological level. To this aim, we
      investigate neural mechanisms underlying the Deutsch's illusion, a condition in
      which both sound identity ("what") and origin ("where") are deceptively
      perceived. We recorded magnetoencephalogram from healthy subjects in three
      conditions: (a) listening to the acoustic sequence eliciting the illusion (ILL),
      (b) listening to a monaural acoustic sequence mimicking the illusory percept
      (MON), and (c) listening to an acoustic sequence similar to (a) but not eliciting
      the illusion (NIL). Results show that the areas involved in the illusion were the
      Heschl's gyrus, the insular cortex, the inferior frontal gyrus, and the medial
      frontal gyrus bilaterally, together with the left inferior-parietal lobe. These
      areas belong to the two main auditory streams known as the what and where
      pathways. The neural responses there observed indicate that the sound sequence
      eliciting the illusion is associated to larger activity at early and middle
      latencies and to a dynamic lateralization pattern net in favor of the left
      hemisphere. The present findings extend to illusory perception the well-known
      what-where auditory processing mechanism, especially as regards tardy latency
      activity.

PMID- 29071386
TI  - 3D Fast Spin-Echo T1 Black-Blood Imaging for the Preoperative Detection of Venous
      Sinus Invasion by Meningioma : Comparison with Contrast-Enhanced MRV.
AB  - OBJECTIVES: To prospectively evaluate the diagnostic value of 3D fast spin-echo
      (FSE) T1 black-blood magnetic resonance (MR) imaging (3D CUBE T1WI) in comparison
      with contrast-enhanced MR venography (CE-MRV) in the detection of sinus invasion
      by meningiomas. METHODS: In this study forty consecutive patients with suspected
      meningiomas adjacent to venous sinus underwent conventional MR imaging, CE-MRV
      and 3D CUBE T1WI scans. Images obtained by each technique were assessed
      independently by two neuroradiologists for (1) wall invasion and (2) lumen
      occlusion of the target venous sinus. RESULTS: The use of 3D CUBE T1W imaging was
      found to provide an easy way to detect the venous wall invasion by para-sinus
      lesions. The interobserver agreement was excellent (kappa = 0.843; 95% confidence
      interval CI 0.757-0.929) and the result was highly consistent with the surgical
      findings (sensitivity 90.48%, specificity 94.12%). In the analysis of the lumen
      occlusion, the interobserver agreement obtained by 3D CUBE T1WI sequence was
      excellent (kappa = 0.956; 95% CI, 0.913-0.999) with a diagnostic accuracy of
      94.74%, which surpassed CE-MRV not only in interobserver agreement (kappa =
      0.736; 95% CI, 0.639-0.833) but also in diagnostic value (accuracy = 68.42%).
      Among 38 patients with meningiomas, the existence and extent of peritumoral edema
      did not correlate with the invasion of adjacent venous sinus. CONCLUSION:
      Currently, 3D CUBE T1WI sequence is a reliable technique to provide accurate
      assessment about the venous sinus invasion by meningioma. Meanwhile, CE-MRV is
      more suitable in the evaluation of the bypass draining veins around the tumor.

PMID- 29071384
TI  - Microcystin-leucine-arginine causes blood-testis barrier disruption and
      degradation of occludin mediated by matrix metalloproteinase-8.
AB  - Microcystin-leucine-arginine (MC-LR) can cause male reproductive disorders.
      However, the underlying mechanisms are not yet fully understood. In this study,
      we aimed to investigate the effects of MC-LR on the integrity of blood-testis
      barrier (BTB) and the related molecular mechanisms. Both transepithelial
      electrical resistance measurement in vitro and electron microscope observation ex
      vivo revealed that MC-LR caused disruption of the tight junction between Sertoli
      cells, which was paralleled by the degradation of occludin. We observed increased
      expression of matrix metalloproteinase-8 (MMP-8) upon exposure to MC-LR, and
      confirmed that abrogation of MMP-8 activity by specific inhibitors as well as
      transfection with MMP-8 shRNA could abolish the degradation of occludin. Our data
      demonstrated that MC-LR up-regulated nuclear levels of c-Fos and c-Jun through
      activating ERK and JNK, and increased NF-kappaB levels by activating the
      phosphatidylinositol 3-kinase (PI3K)/AKT cascades. Enhanced binding of c-Fos and
      NF-kappaB to the promoter of MMP-8 promoted the transcription of MMP-8 gene.
      Furthermore, miR-184-3p was significantly downregulated in SC following exposure
      to MC-LR through targeting MMP-8 expression. Together, these results confirmed
      that MC-LR-induced MMP-8 expression was regulated at both transcriptional and
      post-transcriptional levels, which was involved in MC-LR-induced degradation of
      occludin and BTB destruction. This work may provide new perspectives in
      developing new diagnosis and treatment strategies for MC-induced male
      infertility.

PMID- 29071387
TI  - [Ventricular arrhythmias : What has been confirmed in therapy?]
AB  - Ventricular arrhythmias include a wide range of potentially benign single
      ventricular premature contractions to ventricular tachycardia and ventricular
      fibrillation with a risk for sudden cardiac death. The diagnosis of ventricular
      arrhythmia is made by 12-lead electrocardiogram, 24 h Holter monitoring, an
      external or implantable loop recorder, or during in-hospital monitoring.
      Especially the diagnosis of wide complex tachycardias is challenging in terms of
      differentiating between ventricular tachycardia and supraventricular tachycardia
      with aberrant atrioventricular conduction. After documentation of ventricular
      arrhythmias, diagnostic work-up with respect to structural or electrical
      cardiomyopathy is mandatory followed by risk stratification for sudden cardiac
      death. Therapeutic options for treatment of ventricular arrhythmias range from
      pharmacological therapy and interventional procedures such as catheter ablation
      and implantable devices. The current article provides an overview of the
      diagnosis of ventricular tachycardia and underlying cardiomyopathies.
      Furthermore, medical and interventional therapies are described. In addition, the
      indications for implantable and wearable defibrillators are presented.

PMID- 29071388
TI  - [Advance directives in clinical practice : Living will, healthcare power of
      attorney and care directive].
AB  - In clinical practice, situations continuously occur in which medical
      professionals and family members are confronted with decisions on whether to
      extend or limit treatment for severely ill patients in end of life treatment
      decisions. In these situations, advance directives are helpful tools in decision
      making according to the wishes of the patient; however, not every patient has
      made an advance directive and in our experience medical staff as well as patients
      are often not familiar with these documents. The purpose of this article is
      therefore to explain the currently available documents (e.g. living will,
      healthcare power of attorney and care directive) and the possible (legal)
      applications and limitations in the routine clinical practice.

PMID- 29071385
TI  - Protein kinase D inhibitor CRT0066101 suppresses bladder cancer growth in vitro
      and xenografts via blockade of the cell cycle at G2/M.
AB  - The protein kinase D (PKD) family of proteins are important regulators of tumor
      growth, development, and progression. CRT0066101, an inhibitor of PKD, has
      antitumor activity in multiple types of carcinomas. However, the effect and
      mechanism of CRT0066101 in bladder cancer are not understood. In the present
      study, we show that CRT0066101 suppressed the proliferation and migration of four
      bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked
      tumor growth in a mouse flank xenograft model of bladder cancer. To further
      assess the role of PKD in bladder carcinoma, we examined the three PKD isoforms
      and found that PKD2 was highly expressed in eight bladder cancer cell lines and
      in urothelial carcinoma tissues from the TCGA database, and that short hairpin
      RNA (shRNA)-mediated knockdown of PKD2 dramatically reduced bladder cancer growth
      and invasion in vitro and in vivo, suggesting that the effect of the compound in
      bladder cancer is mediated through inhibition of PKD2. This notion was
      corroborated by demonstrating that the levels of phospho-PKD2 were markedly
      decreased in CRT0066101-treated bladder tumor explants. Furthermore, our cell
      cycle analysis by flow cytometry revealed that CRT0066101 treatment or PKD2
      silencing arrested bladder cancer cells at the G2/M phase, the arrest being
      accompanied by decreases in the levels of cyclin B1, CDK1 and phospho-CDK1
      (Thr161) and increases in the levels of p27Kip1 and phospho-CDK1 (Thr14/Tyr15).
      Moreover, CRT0066101 downregulated the expression of Cdc25C, which
      dephosphorylates/activates CDK1, but enhanced the activity of the checkpoint
      kinase Chk1, which inhibits CDK1 by phosphorylating/inactivating Cdc25C. Finally,
      CRT0066101 was found to elevate the levels of Myt1, Wee1, phospho-Cdc25C
      (Ser216), Gadd45alpha, and 14-3-3 proteins, all of which reduce the CDK1-cyclin
      B1 complex activity. These novel findings suggest that CRT0066101 suppresses
      bladder cancer growth by inhibiting PKD2 through induction of G2/M cell cycle
      arrest, leading to the blockade of cell cycle progression.

PMID- 29071389
TI  - [Graft aneurysms as long-term complication of polyester prostheses and their
      management : Brief review based on a systematic review of the literature].
AB  - INTRODUCTION: A material-associated true aneurysm after previous use of a
      vascular prosthesis for arterial reconstruction mostly in peripheral arterial
      occlusion disease (PAOD) is considered a rare but serious complication. AIM AND
      METHOD: The aim of the compact brief review was to describe the rare finding of a
      true aneurysm of a prosthesis and its diagnosis-specific care including a
      representative scientific case report, based on selected topic-related references
      from the medical literature as well as the specific experiences obtained from the
      successful clinical management in single cases. RESULTS (COMPLEX KEY POINTS
      ASSOCIATED WITH PATIENT AND CLINICAL FINDINGS AND CASE PRESENTATION): Out of
      initially 321 references found in the literature search, 20 articles published
      after 1995 were finally evaluated. Most frequently, pseudoaneurysms of knitted
      polyester prostheses at the femoropopliteal segment occurred on average after
      approximately 12.9 years. In one third of the cases two or more aneurysms of
      Dacron prostheses were described. Histological and electron microscopy
      investigations revealed mainly breakage of filaments and foreign body reactions.
      In more than half of the patients, the aneurysm was resected and for
      reconstruction an interposition graft was implanted. Complete removal of the
      prosthesis and endovascular treatment were only second choice. REPRESENTATIVE
      CASE: A 49-year-old male patient underwent a femoropopliteal P1 prosthetic bypass
      of the right leg in 1997. After 19 years a true aneurysm of the prosthesis was
      diagnosed in the right thigh using duplex ultrasonography and complementary
      magnetic resonance angiography (MRA). This was successfully treated with
      resection of the aneurysm and insertion of an 8-mm Dacron prosthesis (Intergard
      Synergy Knitted, InterVascular, Bensheim, Germany). CONCLUSION: The development
      of true aneurysms of prostheses has not yet been satisfactorily clarified. This
      belongs to the profile of late complications, even if rarely and should be
      controlled after a postoperative interval of approximately one decade. This
      should be carried out by diagnostic imaging follow-up screening if the previous
      arterial recanalization/reconstruction could not be performed sequentially
      following endovascular intervention and venous-based reconstruction, other than
      with prosthetic material.

PMID- 29071391
TI  - Immunometabolism, pregnancy, and nutrition.
AB  - The emerging field of immunometabolism has substantially progressed over the last
      years and provided pivotal insights into distinct metabolic regulators and
      reprogramming pathways of immune cell populations in various immunological
      settings. However, insights into immunometabolic reprogramming in the context of
      reproduction are still enigmatic. During pregnancy, the maternal immune system
      needs to actively adapt to the presence of the fetal antigens, i.e., by
      functional modifications of distinct innate immune cell subsets, the generation
      of regulatory T cells, and the suppression of an anti-fetal effector T cell
      response. Considering that metabolic pathways have been shown to affect the
      functional role of such immune cells in a number of settings, we here review the
      potential role of immunometabolism with regard to the molecular and cellular
      mechanisms necessary for successful reproduction. Since immunometabolism holds
      the potential for a therapeutic approach to alter the course of immune diseases,
      we further highlight how a targeted metabolic reprogramming of immune cells may
      be triggered by maternal anthropometric or nutritional aspects.

PMID- 29071390
TI  - [Current indications for left atrial appendage occlusion].
AB  - Among patients with atrial fibrillation, the bleeding risk is linked to the
      stroke risk. Left atrial appendage (LAA) occlusion may reduce bleeding risk in
      high-risk patients. On the basis of a literature analysis and the Consensus
      Document of European Heart Rhythm Association (EHRA), the indications for a LAA
      occluder are clarified and a clear decision strategy for daily clinical practice
      is presented.

PMID- 29071392
TI  - A transcriptome-SNP-derived linkage map of Apios americana (potato bean) provides
      insights about genome re-organization and synteny conservation in the phaseoloid
      legumes.
AB  - KEY MESSAGE: We report a linkage map for Apios americana and describe synteny
      with selected warm-season legumes. A translocation event in common bean and
      soybean is confirmed against Apios and Vigna species. Apios (Apios americana;
      "apios"), a tuberous perennial legume in the Phaseoleae tribe, was widely used as
      a food by Native Americans. Work in the last 40 years has led to several improved
      breeding lines. Aspects of the pollination biology (complex floral structure and
      tripping mechanism) have made controlled crosses difficult, and the previous
      reports indicated that the plant is likely primarily an outcrosser. We used a
      pseudo-testcross strategy to construct a genetic map specific to the maternal
      parent. The map was built using single-nucleotide polymorphism markers identified
      by comparing the expressed sequences of individuals in the mapping population
      against a de novo maternal reference transcriptome assembly. The apios map
      consists of 11 linkage groups and 1121 recombinationally distinct loci, covering
      ~ 938.6 cM. By sequencing the transcriptomes of all potential pollen parents, we
      were able to identify the probable pollen donors and to discover new aspects of
      the pollination biology in apios. No selfing was observed, but multiple pollen
      parents were seen within individual pods. Comparisons with genome sequences in
      other species in the Phaseoleae showed extended synteny for most apios linkage
      groups. This synteny supports the robustness of the map, and also sheds light on
      the history of the Phaseoleae, as apios is relatively early diverging in this
      tribe. We detected a translocation event that separates apios and two Vigna
      species from Phaseolus vulgaris and Glycine max. This apios mapping work provides
      a general protocol for sequencing-based construction of high-density linkage maps
      in outcrossing species with heterogeneous pollen parents.

PMID- 29071394
TI  - [Study on the prediction of AR-V7 and CTC circulation in patients with
      metastatic, castration-resistant prostate cancer (mCRPC) : Correlation between
      common clinical outcome parameters (rPFS, OS), CTC changes, and AR-V7 status
      (androgen receptor splice variant 7) in patients with mCRPC on first-line therapy
      with abiraterone acetate (STAR-V7)-study AP 96/17 of the AUO].

PMID- 29071393
TI  - Association mapping of drought tolerance-related traits in barley to complement a
      traditional biparental QTL mapping study.
AB  - KEY MESSAGE: Association mapping of drought-related traits in barley was used to
      increase the density of existing QTL maps without recreating mapping populations.
      We used 109 spring barley genotypes exhibiting high or low drought tolerance to
      elucidate the associations between diversity array technology sequencing
      (DArTseq) and single nucleotide polymorphism (SNP) markers and various
      physiological parameters related to plant responses to drought conditions. The
      study was performed in controlled conditions (growth chambers), drought tolerance
      was phenotyped in the four-leaf seedlings. We identified 58 associations
      including 34 new markers (i.e., 16 DArTseq and 18 SNP markers). The results for
      three markers were consistent with the data obtained in an earlier traditional
      biparental QTL mapping study. The regions neighboring markers on linkage group 2H
      contained the highest number of significant marker-trait associations. Five
      markers related to the photosynthetic activity of photosystem II were detected on
      chromosome 4H. The lowest number of associations were observed for the sequences
      neighboring DArT markers on linkage group 6H. A chromosome 3H region related to
      water use efficiency and net photosynthesis rate in both biparental QTL, and
      association study, may be particularly valuable, as these parameters correspond
      to the ability of plants to remain highly productive under water deficit stress.
      Our findings confirm that association mapping can increase the density of
      existing QTL maps without recreating mapping populations.

PMID- 29071395
TI  - [25 years of Integral Theory by Petros : What remains and what's next?]
AB  - BACKGROUND: The Integral Theory (IT) states that urinary stress and urge symptoms
      mainly arise from lax suspensory ligaments, which are a consequence of altered
      collagen/elastin. Four important muscle groups (pubococcygeal muscle,
      levatorplate, longitudinal muscle of the anus, and the puborectalis muscle) are
      only able to guarantee the opening and closure mechanism of the bladder, the
      urethra and the anal tube if the suspensory ligaments are intact. The first
      practical application of the IT was the repair of the pubourethral ligament (PUL)
      known as tension-free vaginal tape (TVT). OBJECTIVES: What is the practical
      impact of the IT today? Do lax suspensory ligaments play a role in stress and
      urge urinary incontinence, fecal incontinence, voiding difficulties, and pelvic
      pain? MATERIALS AND METHODS: Evaluation of the literature, data, and experiences
      concerning IT. RESULTS: The pathophysiology of pelvic floor disorders has been
      widely proven and surgical concepts were developed to reconstruct the ligaments
      with the result of regaining function. Suburethral tapes are accepted as the
      standard of care for urinary stress incontinence. In addition, the correction of
      cervical ring defects, the lateral and central cystoceles, the uterosacral
      ligaments, the perineal body, and the rectovaginal fascia were adapted and newly
      developed with the aim of alleviating symptoms. Newly published data prove the
      cure of symptoms in a high percentage of cases. The complex conditions and
      function of the pelvic floor can be understood much better by using the
      diagnostic algorithm and with knowledge of the basic pathophysiology. CONCLUSION:
      The basic IT message: repair the structure (ligaments) and you will restore the
      function is true for all pelvic floor ligaments.

PMID- 29071396
TI  - [Artificial urinary sphincter in women-too uncommon?]
AB  - The artificial urinary sphincter (AUS) is a well-known standard in the therapy of
      male incontinence, but not in females. This review highlights options, results,
      and a critical appraisal of the use of AUS in women.

PMID- 29071397
TI  - [Prophylaxis of recurring low-flow priapism : Experimental botulinum neurotoxin
      injection into the ischiocavernosus muscle].
AB  - The treatment of recurring low-flow priapism with the usual medications is still
      unsatisfactory. The case of an otherwise healthy young man experiencing low-flow
      priapism at the age of 31 is presented. A reason for his condition could not be
      identified. Over the course of several months, he required emergency urological
      treatment more than ten times. Treatment with cyproterone acetate (Androcur(r) 50
      mg/day) stopped the spontaneous erections, but resulted in erectile impotence,
      reduced motivation, decreased interest in sex, weight gain of 10 kg, breast
      enlargement combined with touch sensitivity on both sides, and hair loss on both
      legs. In addition, the patient complained about painful cramps in his pelvic
      muscles. After appropriate explanations he agreed to try botulinum neurotoxin
      injections into both ischiocavernosus muscles. The objective was to reduce muscle
      tone in order to improve venous drainage of blood from the penis. The latest
      relapse of priapism occurred more than 6 months ago.

PMID- 29071398
TI  - [Metastatic castration-resistant prostate cancer : Use of cabazitaxel taking into
      consideration current data].
AB  - BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase
      III studies concerning taxane-based chemotherapy as a treatment option for
      patients with metastatic castration-resistant prostate cancer (mCRPC) were
      presented. OBJECTIVES: The focus is on the clinical impact of these data.
      MATERIALS AND METHODS: A group of German experts in the field of urogenital
      oncologic expertise discussed the clinical impact with respect to the current
      data. RESULTS: The study results support the current clinical data. They confirm
      the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel
      for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment
      option after docetaxel progression. With respect to the performance status of a
      patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.

PMID- 29071399
TI  - Mixed Culture Biocathodes for Production of Hydrogen, Methane, and Carboxylates.
AB  - Formation of hydrogen, methane, and organics at biocathodes is an attractive new
      application of bioelectrochemical systems (BESs). Using mixed cultures, these
      products can be formed at certain cathode potentials using specific operating
      conditions, of which pH is important. Thermodynamically, the reduction of CO2 to
      methane is the most favorable reaction, followed by reduction of CO2 to acetate
      and ethanol, and hydrogen. In practice, however, the cathode potential at which
      these reactions occur is more negative, meaning that more energy is required to
      drive the reaction. Therefore, hydrogen is often found as a second product or
      intermediate in the conversion of CO2 to both methane and carboxylates. In this
      chapter we summarize the inocula used for biocathode processes and discuss the
      achieved conversion rates and cathode potentials for formation of hydrogen,
      methane, and carboxylates. Although this overview reveals that BESs offer new
      opportunities for the bioproduction of different compounds, there are still
      challenges that need to be overcome before these systems can be applied on a
      larger scale. Graphical Abstract.

PMID- 29071400
TI  - Microbial Electrosynthesis I: Pure and Defined Mixed Culture Engineering.
AB  - In the past 6 years, microbial bioelectrochemistry has strongly increased in
      attraction and audience when expanding from mainly environmental technology
      applications to biotechnology. In particular, the promise to combine
      electrosynthesis with microbial catalysis opens attractive approaches for new
      sustainable redox-cofactor recycling, redox-balancing, or even biosynthesis
      processes. Much of this promise is still not fulfilled, but it has opened and
      fueled entirely new research areas in this discipline. Activities in designing,
      tailoring, and applying specific microbial catalysts as pure or defined co
      cultures for defined target bioproductions are greatly accelerating. This chapter
      gives an overview of the current progress as well as the emerging trends in
      molecular and ecological engineering of defined microbial biocatalysts to prepare
      them for evolving microbial electrosynthesis processes. In addition, the
      multitude of microbial electrosynthetic processes with complex undefined mixed
      cultures is covered by ter Heijne et al. (Adv Biochem Eng Biotechnol.
      https://doi.org/10.1007/10_2017_15 , 2017). Graphical Abstract.

PMID- 29071401
TI  - Lignocellulose-Biorefinery: Ethanol-Focused.
AB  - The development prospects of the world markets for petroleum and other liquid
      fuels are diverse and partly contradictory. However, comprehensive changes for
      the energy supply of the future are essential. Notwithstanding the fact that
      there are still very large deposits of energy resources from a geological point
      of view, the finite nature of conventional oil reserves is indisputable. To
      reduce our dependence on oil, the EU, the USA, and other major economic zones
      rely on energy diversification. For this purpose, alternative materials and
      technologies are being sought, and is most obvious in the transport sector. The
      objective is to progressively replace fossil fuels with renewable and more
      sustainable fuels. In this respect, biofuels have a pre-eminent position in terms
      of their capability of blending with fossil fuels and being usable in existing
      cars without substantial modification. Ethanol can be considered as the primary
      renewable liquid fuel. In this chapter enzymes, micro-organisms, and processes
      for ethanol production based on renewable resources are described.

PMID- 29071402
TI  - Acquired Genetic and Epigenetic Variation in Human Pluripotent Stem Cells.
AB  - Human pluripotent stem cells (hPSCs) can acquire non-random genomic variation
      during culture. Some of these changes are common in tumours and confer a
      selective growth advantage in culture. Additionally, there is evidence that
      reprogramming of human induced pluripotent stem cells (hiPSCs) introduces
      mutations. This poses a challenge to both the safety of clinical applications and
      the reliability of basic research using hPSCs carrying genomic variation. A
      number of methods are available for monitoring the genomic integrity of hPSCs,
      and a balance between practicality and sensitivity must be considered in choosing
      the appropriate methods for each use of hPSCs. Adjusting protocols by which hPSCs
      are derived and cultured is an evolving process that is important in minimising
      acquired genomic variation. Assessing genetic variation for its potential impact
      is becoming increasingly important as techniques to detect genome-wide variation
      improve.

PMID- 29071404
TI  - Scalable Cardiac Differentiation of Pluripotent Stem Cells Using Specific Growth
      Factors and Small Molecules.
AB  - The envisioned routine application of human pluripotent stem cell (hPSC)-derived
      cardiomyocytes (CMs) for therapies and industry-compliant screening approaches
      will require efficient and highly reproducible processes for the mass production
      of well-characterized CM batches.On their way toward beating CMs, hPSCs initially
      undergo an epithelial-to-mesenchymal transition into a primitive-streak (PS)-like
      population that later gives rise to all endodermal and mesodermal lineages,
      including cardiovascular progenies (CVPs). CVPs are multipotent and possess the
      capability to give rise to all major cell types of the heart, including CMs,
      endothelial cells, cardiac fibroblasts, and smooth muscle cells. This article
      provides an historical overview and describes the stepwise development of
      protocols that typically result in the appearance of beating CMs within 7-12 days
      of hPSC differentiation.We describe the development of directed and closely
      controlled cardiomyogenic differentiation, which now enables the induction of
      >90% CM purity without further lineage enrichment. Although secreted lineage
      specifiers (revealed from developmental biology) were initially used, we outline
      the advantages of chemical pathway modulators, as defined by more recent
      screening approaches. Subsequently, we discuss the use of defined culture media
      for upscaling the production of hPSC-CMs in controlled bioreactors and how this,
      in principle, unlimited source of human CMs can be used to progress heart
      regeneration and stimulate the drug discovery pipeline. Graphical Abstract.

PMID- 29071403
TI  - Specific Cell (Re-)Programming: Approaches and Perspectives.
AB  - Many disorders are manifested by dysfunction of key cell types or their disturbed
      integration in complex organs. Thereby, adult organ systems often bear restricted
      self-renewal potential and are incapable of achieving functional regeneration.
      This underlies the need for novel strategies in the field of cell (re
      )programming-based regenerative medicine as well as for drug development in
      vitro. The regenerative field has been hampered by restricted availability of
      adult stem cells and the potentially hazardous features of pluripotent embryonic
      stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Moreover, ethical
      concerns and legal restrictions regarding the generation and use of ESCs still
      exist. The establishment of direct reprogramming protocols for various
      therapeutically valuable somatic cell types has overcome some of these
      limitations. Meanwhile, new perspectives for safe and efficient generation of
      different specified somatic cell types have emerged from numerous approaches
      relying on exogenous expression of lineage-specific transcription factors, coding
      and noncoding RNAs, and chemical compounds.It should be of highest priority to
      develop protocols for the production of mature and physiologically functional
      cells with properties ideally matching those of their endogenous counterparts.
      Their availability can bring together basic research, drug screening, safety
      testing, and ultimately clinical trials. Here, we highlight the remarkable
      successes in cellular (re-)programming, which have greatly advanced the field of
      regenerative medicine in recent years. In particular, we review recent progress
      on the generation of cardiomyocyte subtypes, with a focus on cardiac pacemaker
      cells. Graphical Abstract.

PMID- 29071405
TI  - Requirements for Using iPSC-Based Cell Models for Assay Development in Drug
      Discovery.
AB  - A prevalent challenge in drug discovery is the translation of findings from
      preclinical research into clinical success. Currently, more physiological in
      vitro systems are being developed to overcome some of these challenges. In
      particular, induced pluripotent stem cells (iPSCs) have provided the opportunity
      to generate human cell types that can be utilized for developing more disease
      relevant cellular assay models. As the use of these complex models is lengthy and
      fairly complicated, we lay out our experiences of the cultivation,
      differentiation, and quality control requirements to successfully utilize
      pluripotent stem cells in drug discovery.

PMID- 29071406
TI  - Extracellular Electron Transfer and Biosensors.
AB  - This chapter summarizes in the beginning our current understanding of
      extracellular electron transport processes in organisms belonging to the genera
      Shewanella and Geobacter. Organisms belonging to these genera developed
      strategies to transport respiratory electrons to the cell surface that are
      defined by modules of which some seem to be rather unique for one or the other
      genus while others are similar. We use this overview regarding our current
      knowledge of extracellular electron transfer to explain the physiological
      interaction of microorganisms in direct interspecies electron transfer, a process
      in which one organism basically comprises the electron acceptor for another
      microbe and that depends also on extended electron transport chains. This
      analysis of mechanisms for the transport of respiratory electrons to insoluble
      electron acceptors ends with an overview of questions that remain so far
      unanswered. Moreover, we use the description of the biochemistry of extracellular
      electron transport to explain the fundamentals of biosensors based on this
      process and give an overview regarding their status of development and
      applicability. Graphical Abstract.

PMID- 29071407
TI  - Recombinant Proteins and Monoclonal Antibodies.
AB  - The human genome has become a subject of public interest, whilst the proteome
      remains the province of specialists. Less appreciated is the human glycoprotein
      (GP) repertoire (proteoglycome!); however, some 50% of open reading frame genes
      encode for proteins (P) that may accept the addition of N-linked and/or O-linked
      sugar chains (oligosaccharides). It is established that the attachment of defined
      oligosaccharide structures impacts mechanisms of action (MoAs), pharmacokinetics,
      pharmacodynamics, etc., and is a critical quality attribute (CQA) for recombinant
      GP therapeutics. The oligosaccharide structure attached at a given site may
      exhibit structural heterogeneity, and individual structures (glycoforms) may
      modulate MoAs. The biopharmaceutical industry is challenged, therefore, to
      produce recombinant GP therapeutics that have structural fidelity to the natural
      (endogenous) molecule, in non-human cells. Multiple production platforms have
      been developed that, in addition to the natural glycoform, may produce unnatural
      glycoforms, including sugar residues that can be immunogenic in human subjects.
      Following a general introduction to the field, this review discusses
      glycosylation of recombinant monoclonal antibodies (mAbs), the contribution of
      glycoforms to MoAs and the development of customised mAb therapeutic glycoforms
      to optimise MoAs for individual disease indications.

PMID- 29071408
TI  - Comment on "Do we have the right PROMs for measuring outcomes in lumbar spinal
      surgery?" by O. M. Stokes et al. Eur Spine J. 2017 Mar;26(3):816-824.

PMID- 29071409
TI  - Prospective randomized controlled comparison of posterior vs. posterior-anterior
      stabilization of thoracolumbar incomplete cranial burst fractures in neurological
      intact patients: the RASPUTHINE pilot study.
AB  - PURPOSE: If surgery for thoracolumbar incomplete cranial burst fractures (Magerl
      A3.1.1) is necessary, the ideal stabilization strategy still remains
      undetermined. To justify posterior-anterior stabilization, which generates higher
      costs and potentially higher morbidity vs. posterior-only stabilization, clinical
      trials with sufficient power and adequate methodology are required. This
      prospective randomized single-centre pilot trial was designed to enable
      sufficient sample-size calculation for a randomized multicentre clinical trial
      (RASPUTHINE). METHODS: Patients with a traumatic thoracolumbar (Th11-L2)
      incomplete burst fracture (Magerl A3.1.1) were randomly assigned either to the
      interventional group (posterior-anterior) or to the control group (posterior
      only). Primary endpoint of the study was the clinical outcome measured using the
      Oswestry Disability Index (ODI) at 24 months. Radiological outcome was assessed
      as secondary endpoint by evaluation of mono- and bisegmental kyphotic angulation
      and monosegmental fusion. RESULTS: 21 patients were randomly assigned to
      interventional group (n = 9) or control group (n = 12). One posterior-only
      treated patient showed a severe initial loss of correction resulting in a
      crossover to additional anterior bisegmental fusion. The ODI measures at the
      primary study endpoint showed less but insignificant (p = 0.67) disability for
      the interventional group over the control group (13.3 vs. 19.3%). Comparison of
      preoperative bisegmental kyphosis in supine position with the bisegmental
      kyphosis at 24-month FU in upright position showed a worsened kyphosis for the
      control group (10.7 degrees  -> 15.6 degrees ), whereas an improved kyphosis (11
      degrees  -> 8.3 degrees ) was detectable for the interventional group.
      CONCLUSION: The results of this pilot RCT showed less disability for the
      posterior-anterior group linked with a significant better restoration of the
      sagittal profile in comparison with the posterior-only group. To detect a
      clinically significant difference using the ODI and assuming a 20% loss of FU
      rate, a total of 266 patients have to be studied in the multicentre trial.

PMID- 29071410
TI  - Effects of lumbosacral orthoses on postural control in individuals with or
      without non-specific low back pain.
AB  - OBJECTIVE: To investigate the effect of lumbosacral orthoses (LSOs) on postural
      control in individuals with or without non-specific low back pain (NSLBP).
      METHODS: Individuals with NSLBP (n = 28) and healthy controls (n = 28) were
      enrolled to assess the postural control with or without LSOs. Postural control
      was tested using the Balance Master(r) NeuroCom system by the modified clinical
      test of sensory interaction and balance. RESULTS: Relative to controls, patients
      with NSLBP had deficits in postural control with greater center of pressure (COP)
      sway velocity when standing on firm surface (with eyes open: p = 0.002; with eyes
      closed: p = 0.002) and standing on foam surface (with eyes open: p = 0.024; with
      eyes closed: p < 0.001). In the braced condition, the COP sway decreased in all
      subjects with or without NSLBP when standing on foam surface. There was no
      significant difference in the effect of LSOs on postural control between NSLBP
      group and healthy controls. CONCLUSION: Individuals with NSLBP have poorer
      postural control than controls. LSOs seem to improve postural control when
      standing on unstable surfaces in subjects with or without NSLBP. The effect of
      LSOs on postural control may not depend on the level of baseline.

PMID- 29071411
TI  - A comparison of the type IX collagen levels of the intervertebral disc materials
      in diabetic and non-diabetic patients who treated with lumbar microdiscectomy.
AB  - PURPOSE: The purpose of this study was to compare type IX collagen levels in the
      intervertebral disc (IVD) materials of diabetic and non-diabetic patients with
      lumbar disc herniation and to determine whether there is a relationship between
      diabetes mellitus (DM) and type IX collagen levels in degenerated discs. METHODS:
      Overall, 30 non-diabetic patients and 30 type II diabetic patients who underwent
      lumbar microdiscectomy were included in this study. All patients underwent lumbar
      microdiscectomy, and IVD samples were obtained during the surgery.
      Deparaffinization, macroscopic digestion, and staining procedures were performed
      immunohistochemically. Fractional area stained, staining intensity, and total
      staining score were graded semi-quantitatively. The results were evaluated within
      a 95% confidence interval, and significance was evaluated as bidirectional at
      0.05 and 0.01 significance levels. RESULTS: The type IX collagen staining
      intensities and fractional area stained were lower in the diabetic group than
      those in the non-diabetic group (p = 0.001). The total immunoreactivity staining
      scores of type IX collagen in the diabetic group were statistically lower at
      higher significance levels than the total immunoreactivity staining scores of
      type IX collagen in the non-diabetic group (p = 0.001). The duration of DM of the
      patients with DM was increased, the total immunoreactivity staining score of type
      IX collagen was decreased (p = 0.001). CONCLUSIONS: Diabetes reduces the type IX
      collagen level in the intervertebral disc and the duration of diabetes is the
      most important factor for this reduction. Diabetes may play a role in the
      development of disc herniation by reducing type IX collagen levels in the
      intervertebral disc. However, the causes of increased herniation in diabetic
      patients still have to be determined.

PMID- 29071413
TI  - Phase II study of fixed dose-rate gemcitabine plus S-1 as a second-line treatment
      for advanced biliary tract cancer.
AB  - PURPOSE: Gemcitabine plus platinum is considered standard first-line chemotherapy
      for patients with advanced biliary tract cancer. However, no standard second-line
      therapy has been established for this disease. According to reports, S-1 exerts
      anti-tumor effects on advanced biliary tract cancer and gemcitabine is more
      effective via fixed dose-rate administration. We evaluated the efficacy and
      safety of a combination of fixed dose-rate gemcitabine and S-1 after failure of
      gemcitabine or gemcitabine plus cisplatin therapy. METHODS: This single-arm phase
      II study (clinical trial number: UMIN000005918) set the response rate as the
      primary endpoint and used a MiniMax two-stage design with a null hypothesis < 7%
      and alternative hypothesis >= 25%. Thirty-five patients were needed to yield a
      power of 90% and alpha value of 0.05. Patients received gemcitabine (1000 mg/m2,
      div, 100-min period, day 1) and S-1 (40 mg/m2 twice daily, oral, days 1-7), every
      2 weeks until disease progression or intolerable adverse events were observed.
      RESULTS: Forty-one patients were enrolled, and 3 of 23 first-stage patients
      responded. The overall response rate was 9.8% [95% confidence interval (CI): 2.7
      19.2%]. The median overall and progression-free survival were 7.0 [95% CI: 5.3
      8.6] and 2.6 months (95% CI: 1.6-3.5), respectively. The most common grade 3-4
      adverse events were leukopenia (19.5%), neutropenia (19.5%), anemia (14.6%),
      thrombocytopenia (7.3%), and anorexia (4.8%). CONCLUSION: Second-line fixed dose
      rate gemcitabine plus S-1 was not sufficiently effective and tolerable in
      patients with advanced biliary tract cancer refractory to gemcitabine or
      gemcitabine plus cisplatin.

PMID- 29071415
TI  - Correction to: Safety and effectiveness of self-adhesive mesh in laparoscopic
      ventral hernia repair using transabdominal preperitoneal route.
AB  - The metadata listed the wrong given names and family names.

PMID- 29071416
TI  - Feasibility and safety of a novel magnetic-assisted capsule endoscope system in a
      preliminary examination for upper gastrointestinal tract.
AB  - BACKGROUND AND STUDY AIM: Current capsule endoscopy procedures are ineffective
      for upper gastrointestinal (GI) tract examination because they do not allow for
      operator-controlled navigation of the capsule. External controllability of a
      capsule endoscope with an applied magnetic field is a possible solution to this
      problem. We developed a novel magnetic-assisted capsule endoscope (MACE) system
      to visualize the entire upper GI tract. The present study evaluated the safety
      and feasibility of the MACE system for the examination of the upper GI tract,
      including the esophagus, stomach, and duodenum. METHODS: The present open
      clinical study enrolled ten healthy volunteers. All participants swallowed a
      MACE, and an external magnetic field navigator was used for magnetic capsule
      manipulation in the upper GI tract. We assessed the maneuverability of the
      magnetic capsule and completeness of the MACE examination as well as the safety
      and tolerability of the procedure. RESULTS: The present study enrolled ten
      healthy volunteers with a mean age and body mass index of 47.7 years and 25.6
      kg/m2, respectively. One volunteer withdrew because of difficulty in swallowing
      the capsule. In total, nine volunteers underwent the MACE examination. The
      average examination time was 27.1 min. The maneuverability of the capsule was
      assessed as good and fair in 55.6 and 44.4% of the participants, respectively.
      The overall completeness of the examination in the esophagus, stomach, and
      duodenum was 100, 85.2, and 86.1%, respectively. No severe adverse events
      occurred during this study. All participants exhibited satisfactory tolerance of
      the MACE examination. CONCLUSION: The MACE system has satisfactory
      maneuverability and visualization completeness with excellent acceptance and
      tolerance.

PMID- 29071414
TI  - A non-randomized, open-label, single-arm, Phase 2 study of emibetuzumab in Asian
      patients with MET diagnostic positive, advanced gastric cancer.
AB  - PURPOSE: Mesenchymal-epithelial transition factor (MET) is expressed in gastric
      cancer and associated with poor clinical outcomes. We assessed activity, safety,
      and pharmacokinetics of emibetuzumab, a bivalent monoclonal anti-MET antibody
      that blocks ligand-dependent and ligand-independent MET signaling. METHODS: This
      non-randomized, single-arm, Phase 2 study enrolled Asian patients with MET
      diagnostic positive advanced gastric adenocarcinoma. Emibetuzumab (2000 mg,
      intravenous) was given on days 1 and 15 (28-day cycle). The primary endpoint was
      8-week progression-free survival rate. Secondary objectives included safety,
      pharmacokinetics, overall survival, and change in tumor size. RESULTS: Tumors
      from 65 patients were immunohistochemically screened to enroll 15 MET diagnostic
      positive patients (23% positivity; 8 Japanese, 7 Korean; 10 male). Eight-week
      progression-free survival rate was 0.47 (70% CI, 0.33-0.59). Disease control rate
      was 40% (target lesion decreases, three patients; no complete/partial responses
      according to RECIST). Median overall survival was 17.1 weeks (95% CI, 6.3-not
      achievable). No serious emibetuzumab-related adverse events or new safety signals
      emerged. Grade >= 3 possibly drug-related adverse events were hyperkalemia,
      hyponatremia, and hyperuricemia (one each). Emibetuzumab's pharmacokinetics
      profile was similar to that observed previously. MET expression and clinical
      outcomes were not obviously associated. CONCLUSION: Emibetuzumab was well
      tolerated with limited single-agent activity in advanced gastric adenocarcinoma.

PMID- 29071417
TI  - The advantages of transumbilical single-site laparoscopic percutaneous
      extraperitoneal closure for inguinal hernia in 1583 children.
AB  - BACKGROUND: There have been numerous surgical procedures for inguinal hernia in
      children, and recently the novel technique of single-site laparoscopic procedure
      was introduced. This study aimed to analyze the safety and efficacy of single
      site laparoscopic hernia repair in a large number of children, while compared
      with the traditional open surgery. METHODS: From January 2012 to June 2015, we
      performed transumbilical single-site laparoscopic percutaneous extraperitoneal
      closure (TSLPEC) in 1583 patients, including bilateral hernia in 135 cases, and
      unilateral hernia in 1448 cases (left side in 582, right side in 866). From
      January 2007 to January 2010, we performed open inguinal hernia repair in 355
      patients, including bilateral hernia in 52 cases, and unilateral hernia in 303
      cases. Operating time, recurrence rate, incidence of contralateral hernia, and
      prevalence of contralateral patent processus vaginalis (cPPV) were recorded and
      compared. RESULTS: A total of 1583 patients underwent TSLPEC, without conversion
      to open surgery. For unilateral repair, the average operating time in TSLPEC
      group was shorter than open repair group (19.3 +/- 6.1 vs. 28.0 +/- 8.9, p <
      0.05), and it was much shorter than open repair group for bilateral repair (26.2
      +/- 9.5 vs. 49.8 +/- 12.9, P p < 0). The left hernia had higher prevalence of
      cPPV than right hernia (48.1% vs. 38.5%, p < 0.05). The wound recovered well with
      good cosmetic appearance in TSLPEC group. Hernia recurrence occurred in seven
      cases (0.4%) of TSLPEC group, and six cases (1.7%) of open repair group ( p <
      00.05). No contralateral hernia developed in TSLPEC group, while 17 cased (5.6%)
      had contralateral hernia in open repair group ( p < 00.05). CONCLUSIONS: TSLPEC
      is an effective and safe procedure for inguinal hernias with lots of advantages,
      including short operating time, simultaneous management of cPPV, excellent
      cosmetic appearance, low incidence of contralateral hernia, and low recurrence
      rate. This procedure could be recommended as a routine treatment for inguinal
      hernias in children.

PMID- 29071418
TI  - Modified liver hanging maneuver focusing on outflow control in pure laparoscopic
      left-sided hepatectomy.
AB  - BACKGROUND: Outflow control during laparoscopic liver resection necessitates the
      use of technically demanding procedures since the hepatic veins are fragile and
      vulnerable to damage during parenchymal transection. The liver hanging maneuver
      reduces venous backflow bleeding during deep parenchymal transection. The present
      report describes surgical outcomes and a technique to achieve outflow control
      during application of the modified liver hanging maneuver in patients undergoing
      laparoscopic left-sided hepatectomy. METHODS: A retrospective review was
      performed of clinical data from 29 patients who underwent laparoscopic left-sided
      hepatectomy using the modified liver hanging maneuver between February 2013 and
      March 2017. For this hanging technique, the upper end of the hanging tape was
      placed on the lateral aspect of the left hepatic vein. The tape was then aligned
      with the ligamentum venosum. The position of the lower end of the hanging tape
      was determined according to left-sided hepatectomy type. The hanging tape
      gradually encircled either the left hepatic vein or the common trunk of the left
      hepatic vein and middle hepatic vein. RESULTS: The surgical procedures comprised:
      left lateral sectionectomy (n = 10); left hepatectomy (n = 17); and extended left
      hepatectomy including the middle hepatic vein (n = 2). Median operative time was
      210 min (range 90-350 min). Median intraoperative blood loss was 200 ml (range 60
      600 ml). Two intraoperative major hepatic vein injuries occurred during left
      hepatectomy. Neither patient developed massive bleeding or air embolism.
      Postoperative major complications occurred in one patient (3.4%). Median
      postoperative hospital stay was 7 days (range 4-15 days). No postoperative
      mortality occurred. CONCLUSIONS: The present modified liver hanging maneuver is a
      safe and effective method of outflow control during laparoscopic left-sided
      hepatectomy.

PMID- 29071419
TI  - Automatically rating trainee skill at a pediatric laparoscopic suturing task.
AB  - BACKGROUND: Minimally invasive surgeons must acquire complex technical skills
      while minimizing patient risk, a challenge that is magnified in pediatric
      surgery. Trainees need realistic practice with frequent detailed feedback, but
      human grading is tedious and subjective. We aim to validate a novel motion
      tracking system and algorithms that automatically evaluate trainee performance of
      a pediatric laparoscopic suturing task. METHODS: Subjects (n = 32) ranging from
      medical students to fellows performed two trials of intracorporeal suturing in a
      custom pediatric laparoscopic box trainer after watching a video of ideal
      performance. The motions of the tools and endoscope were recorded over time using
      a magnetic sensing system, and both tool grip angles were recorded using handle
      mounted flex sensors. An expert rated the 63 trial videos on five domains from
      the Objective Structured Assessment of Technical Skill (OSATS), yielding summed
      scores from 5 to 20. Motion data from each trial were processed to calculate 280
      features. We used regularized least squares regression to identify the most
      predictive features from different subsets of the motion data and then built six
      regression tree models that predict summed OSATS score. Model accuracy was
      evaluated via leave-one-subject-out cross-validation. RESULTS: The model that
      used all sensor data streams performed best, achieving 71% accuracy at predicting
      summed scores within 2 points, 89% accuracy within 4, and a correlation of 0.85
      with human ratings. 59% of the rounded average OSATS score predictions were
      perfect, and 100% were within 1 point. This model employed 87 features, including
      none based on completion time, 77 from tool tip motion, 3 from tool tip
      visibility, and 7 from grip angle. CONCLUSIONS: Our novel hardware and software
      automatically rated previously unseen trials with summed OSATS scores that
      closely match human expert ratings. Such a system facilitates more feedback
      intensive surgical training and may yield insights into the fundamental
      components of surgical skill.

PMID- 29071420
TI  - Venous pressures and cardiac filling in turtles during apnoea and intermittent
      ventilation.
AB  - The amount of blood pumped by the heart (cardiac output) must be matched to the
      amount of blood returning to the heart (venous return), but the factors
      determining cardiac filling are sparsely understood in ectothermic vertebrates.
      Stroke volume is affected by heart rate along with central and peripheral venous
      pressures. In the present study, we investigated the heart rate dependency of
      cardiac filling in turtles, along with the changes in venous pressures that
      accompany ventilation. Experimental reductions in heart rate of anaesthetised
      turtles (Trachemys scripta) by the specific bradycardic agent zatebradine (2-3 mg
      kg-1) resulted in an elevation of stroke volume that compensated cardiac output.
      By contrast, in spontaneously ventilating turtles, stroke volume remained
      constant, even during the transitions from the pronounced bradycardia during
      breath-hold diving to the accelerated heart rate associated with spontaneous
      ventilation. Ventilation was associated with pronounced decreases in visceral,
      pericardial and central venous pressure, all of which became sub-ambient
      (especially during inspiration) and may provide a powerful 'suctional' element to
      cardiac filling. In addition, mean circulatory filling pressure, an index of
      vascular capacitance and the peripheral driving pressure for venous return, was
      increased by infusion of adrenaline (2.5 ug kg-1). Together these data
      demonstrate that changes in both central and peripheral venous pressures are key
      determinants of venous return that, in concert with direct regulation of the
      heart, contribute to the large scope for cardiac output in turtles.

PMID- 29071421
TI  - Effect of drug-loaded TiO2 nanotube arrays on osseointegration in an orthodontic
      miniscrew: an in-vivo pilot study.
AB  - Osseointegration was evaluated for the surface of miniscrews with TiO2 nanotube
      arrays containing drugs in this in-vivo study. The diameter and length of the
      TiO2 nanotube arrays were about 70 nm and 5 MUm, respectively. Recombinant human
      bone morphogenetic protein-2 (rhBMP-2) or ibuprofen was loaded in the TiO2
      nanotube arrays with 12 miniscrews. The 12 drug-loaded miniscrews, 6 miniscrews
      with no drug-loaded TiO2 nanotube arrays and 6 conventional miniscrews, were
      placed on the tibias of New Zealand white rabbits. Histological osseointegration
      was assessed 8 weeks after implantation by measuring the bone-to-implant contact
      (BIC) ratio. Ibuprofen-loaded miniscrews showed a significantly higher BIC of
      71.6% over conventional miniscrews of 44.3% on average. The mean BIC ratios of
      rhBMP-2-loaded miniscrews and no drug-loaded miniscrews was 24.6% and 60.1%,
      respectively. Our results suggest that TiO2 nanotube arrays on the surface of
      miniscrews could be used as carriers of drugs, and loading ibuprofen in TiO2
      nanotube arrays may improve osseointegration of miniscrews. However, the effect
      of rhBMP-2 loaded in TiO2 nanotube arrays on osseointegration of miniscrews was
      questionable in this pilot study.

PMID- 29071423
TI  - Biodegradation and metabolic pathway of sulfamethoxazole by a novel strain
      Acinetobacter sp.
AB  - In this study, a novel strain capable of degrading sulfamethoxazole (SMX) was
      isolated and identified as Acinetobacter sp. The effect of influencing factors,
      such as initial SMX concentration (5-240 mg/L), temperature (15-35  degrees C),
      and pH (5-7), on SMX degradation was investigated. The results showed that when
      the initial SMX concentration was in the range of 5-240, the removal efficiency
      was 100%. The optimal condition for SMX biodegradation and microbial growth was
      determined to be 25  degrees C and pH = 7.0 in terms of the removal efficiencies
      of SMX and total organic carbon (TOC). Four metabolite compounds were detected
      during the process of SMX biodegradation, and the degradation pathways were
      tentatively proposed. In summary, Acinetobacter sp. was highly efficient in
      mineralizing SMX, which has the potential to be used for degrading SMX in water
      and wastewater.

PMID- 29071422
TI  - Reasons and risk factors for ninety day re-admission following primary total knee
      arthroplasty in a high-volume centre.
AB  - PURPOSE: We aimed to assess the rates, reasons, and risk factors for 90-day re
      admissions after total knee arthroplasty (TKA) in a European healthcare setting.
      METHODS: We identified all primary elective TKA procedures performed in 2015 at a
      single high-volume centre. Patients with unplanned re-admissions within 90 days
      of primary discharge were compared to a 1:4 control cohort of patients having no
      relevant re-admission. We calculated re-admission rates, recorded the reasons for
      re-admission, and identified independent predictors of re-admission. RESULTS: The
      30-day and 90-day unplanned re-admission rates were 6.5% and 8.0%, respectively.
      The most common reason for re-admission within 90 days was infection (29.6%),
      followed by knee pain (14.1%), gastrointestinal complications (8.5%), and
      haematoma (8.5%). Multivariable logistic regression analysis revealed that the
      following factors were significant independent predictors of re-admission:
      asthma, psychiatric disease, pre-operative tibiofemoral valgus angle, and pre
      operative knee flexion deficit. CONCLUSIONS: The re-admission rates in our health
      care setting were slightly higher than those previously reported. Independent
      risk factors for re-admissions included pre-operative mechanical axis, range of
      motion, asthma, and psychiatric disease. Our present results will facilitate the
      targeting of new subgroups of TKA patients when developing new interventions to
      further reduce the total re-admission risk after TKA.

PMID- 29071424
TI  - Impact of Trauma System Structure on Injury Outcomes: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: The effectiveness of trauma systems in decreasing injury mortality
      and morbidity has been well demonstrated. However, little is known about which
      components contribute to their effectiveness. We aimed to systematically review
      the evidence of the impact of trauma system components on clinically important
      injury outcomes. METHODS: We searched MEDLINE, EMBASE, Cochrane CENTRAL, and
      BIOSIS/Web of Knowledge, gray literature and trauma association Web sites to
      identify studies evaluating the association between at least one trauma system
      component and injury outcome. We calculated pooled effect estimates using inverse
      variance random-effects models. We evaluated quality of evidence using GRADE
      criteria. RESULTS: We screened 15,974 records, retaining 41 studies for
      qualitative synthesis and 19 for meta-analysis. Two recommended trauma system
      components were associated with reduced odds of mortality: inclusive design (odds
      ratio [OR] = 0.72 [0.65-0.80]) and helicopter transport (OR = 0.70 [0.55-0.88]).
      Pre-Hospital Advanced Trauma Life Support was associated with a significant
      reduction in hospital days (mean difference [MD] = 5.7 [4.4-7.0]) but a
      nonsignificant reduction in mortality (OR = 0.78 [0.44-1.39]). Population density
      of surgeons was associated with a nonsignificant decrease in mortality (MD = 0.58
      [-0.22 to 1.39]). Trauma system maturity was associated with a significant
      reduction in mortality (OR = 0.76 [0.68-0.85]). Quality of evidence was low or
      very low for mortality and healthcare utilization. CONCLUSIONS: This review
      offers low-quality evidence for the effectiveness of an inclusive design and
      trauma system maturity and very-low-quality evidence for helicopter transport in
      reducing injury mortality. Further research should evaluate other recommended
      components of trauma systems and non-fatal outcomes and explore the impact of
      system component interactions.

PMID- 29071425
TI  - Variation with depth of the abundance, diversity and pigmentation of culturable
      bacteria in a deep ice core from the Yuzhufeng Glacier, Tibetan Plateau.
AB  - It has been suggested that the cryosphere is a new biome uniquely dominated by
      microorganisms, although the ecological characteristics of these cold-adapted
      bacteria are not well understood. We investigated the vertical variation with
      depth of the proportion of pigmented bacteria recovered from an ice core drilled
      in the Yuzhufeng Glacier, Tibetan Plateau. A total of 25,449 colonies were
      obtained from 1250 ice core sections. Colonies grew on only one-third of the
      inoculated Petri dishes, indicating that although the ice core harbored abundant
      culturable bacteria, bacteria could not be isolated from every section. Four
      phyla and 19 genera were obtained; Proteobacteria formed the dominant cluster,
      followed by Actinobacteria, Bacteroidetes and Firmicutes. The proportion of
      pigmented bacteria increased with depth from 79 to 95% and yellow-colored
      colonies predominated throughout the ice core, making up 47% of all the colonies.
      Pigments including alpha- and beta-carotene, diatoxanthin, peridinin, zea/lutein,
      butanoyloxy, fucoxanthin and fucoxanthin were detected in representative colonies
      with alpha-carotene being the dominant carotenoid. To the best of our knowledge,
      this is the highest resolution study of culturable bacteria in a deep ice core
      reported to date.

PMID- 29071427
TI  - Adjuvant therapies in critical care: steroids in community-acquired pneumonia.

PMID- 29071426
TI  - Echocardiography in Infective Endocarditis: State of the Art.
AB  - PURPOSE OF REVIEW: In this review, we examine the central role of
      echocardiography in the diagnosis, prognosis, and management of infective
      endocarditis (IE). RECENT FINDINGS: 2D transthoracic echocardiography (TTE) and
      transesophageal echocardiography TEE have complementary roles and are
      unequivocally the mainstay of diagnostic imaging in IE. The advent of 3D and
      multiplanar imaging have greatly enhanced the ability of the imager to evaluate
      cardiac structure and function. Technologic advances in 3D imaging allow for the
      reconstruction of realistic anatomic images that in turn have positively impacted
      IE-related surgical planning and intervention. CT and metabolic imaging appear to
      be emerging as promising ancillary diagnostic tools that could be deployed in
      select scenarios to circumvent some of the limitations of echocardiography. Our
      review summarizes the indispensable and central role of various echocardiographic
      modalities in the management of infective endocarditis. The complementary role of
      2D TTE and TEE are discussed and areas where 3D TEE offers incremental value
      highlighted. An algorithm summarizing a contemporary approach to the workup of
      endocarditis is provided and major societal guidelines for timing of surgery are
      reviewed.

PMID- 29071428
TI  - IgE autoantibodies and their association with the disease activity and phenotype
      in bullous pemphigoid: a systematic review.
AB  - Bullous pemphigoid (BP) is the most common autoimmune skin disease of blistering
      character. The underlying pathophysiological mechanism involves an immune attack,
      usually by IgG class autoantibodies, on the autoantigen BP 180/BPAg2, which is a
      type XVII collagen (COL17) protein acting as the adhesion molecule between the
      epidermis and the basement membrane of the dermis. About 40 years ago, following
      consistent findings of elevated total serum IgE levels in BP patients, it was
      hypothesized that IgE may be involved in the pathophysiology of BP. Our objective
      was to determine whether there is strong evidence for an association between IgE
      class autoantibodies and the clinical severity or phenotype of BP. Three
      databases were searched for relevant studies and appropriate exclusion and
      inclusion criteria were applied. Data was extracted and assessed in relation to
      the study questions concerning the clinical significance of IgE autoantibodies in
      BP. Nine studies found that anti-BP180 autoantibodies of IgE class are associated
      with increased severity of BP, whereas two studies did not find such an
      association. The number of studies which found an association between higher IgE
      autoantibody levels and the erythematous urticarial phenotype of BP (5) was equal
      in number to the studies which found no such association (5). In conclusion,
      higher serum IgE autoantibody levels are associated with more severe clinical
      manifestations of BP. There is insufficient evidence to support higher IgE
      autoantibody levels being associated with specific clinical phenotypes of BP.

PMID- 29071429
TI  - Risk stratification using SpO2/FiO2 and PEEP at initial ARDS diagnosis and after
      24 h in patients with moderate or severe ARDS.
AB  - BACKGROUND: We assessed the potential of risk stratification of ARDS patients
      using SpO2/FiO2 and positive end-expiratory pressure (PEEP) at ARDS onset and
      after 24 h. METHODS: We used data from a prospective observational study in
      patients admitted to a mixed medical-surgical intensive care unit of a university
      hospital in the Netherlands. Risk stratification was by cutoffs for SpO2/FiO2 and
      PEEP. The primary outcome was in-hospital mortality. Patients with moderate or
      severe ARDS with a length of stay of > 24 h were included in this study. Patients
      were assigned to four predefined risk groups: group I (SpO2/FiO2 >= 190 and PEEP
      < 10 cm H2O), group II (SpO2/FiO2 >= 190 and PEEP >= 10 cm), group III (SpO2/FiO2
      < 190 and PEEP < 10 cm H2O) and group IV (SpO2/FiO2 < 190 and PEEP >= 10 cm H2O).
      RESULTS: The analysis included 456 patients. SpO2/FiO2 and PaO2/FiO2 had a strong
      relationship (P < 0.001, R 2 = 0.676) that could be described in a linear
      regression equation (SpO2/FiO2 = 42.6 + 1.0 * PaO2/FiO2). Risk stratification at
      initial ARDS diagnosis resulted in groups that had no differences in in-hospital
      mortality. Risk stratification at 24 h resulted in groups with increasing
      mortality rates. The association between group assignment at 24 h and outcome was
      confounded by several factors, including APACHE IV scores, arterial pH and plasma
      lactate levels, and vasopressor therapy. CONCLUSIONS: In this cohort of patients
      with moderate or severe ARDS, SpO2/FiO2 and PaO2/FiO2 have a strong linear
      relationship. In contrast to risk stratification at initial ARDS diagnosis, risk
      stratification using SpO2/FiO2 and PEEP after 24 h resulted in groups with
      worsening outcomes. Risk stratification using SpO2/FiO2 and PEEP could be
      practical, especially in resource-limited settings.

PMID- 29071431
TI  - Lower serotonin transporter binding in patients with cervical dystonia is
      associated with psychiatric symptoms.
AB  - BACKGROUND: Cervical dystonia (CD) is often accompanied by depressive symptoms,
      anxiety, and jerks/tremor. The dopamine transporter (DAT) binding is related with
      both depressive symptoms and jerks/tremor in CD. Serotonergic and dopaminergic
      systems are closely related. As serotonin is involved in the pathophysiology of
      psychiatric symptoms and jerks, we expected an altered serotoninergic system in
      CD. We hypothesized that CD is associated with reduced serotonin transporter
      (SERT) binding, more specific that SERT binding is lower in CD patients with
      psychiatric symptoms and/or jerks/tremor compared to those without, and to
      controls. The balance between SERT and DAT binding can be altered in different CD
      phenotypes. RESULTS: In 23 CD patients and 14 healthy controls, SERT binding in
      the diencephalon/midbrain was assessed using [123I]FP-CIT SPECT, with a brain
      dedicated system. The specific to non-specific binding ratio (binding potential;
      BPND) to SERT was the main outcome measure. There was a clear trend towards
      reduced SERT BPND in CD patients with psychiatric symptoms compared to those
      without (p = 0.05). There was no correlation between SERT binding and dystonia,
      jerks, or anxiety. There was a significant positive correlation between
      extrastriatal SERT and striatal DAT BPND in CD patients with jerks, but not in
      patients without jerks. CONCLUSION: CD patients with psychiatric symptoms have
      lower SERT binding in the midbrain/diencephalon, while dystonia and jerks appear
      unrelated to SERT binding. The balance between extrastriatal SERT and striatal
      DAT binding is different in CD with and without jerks.

PMID- 29071430
TI  - Functional Information in Coronary Artery Disease: The Case of Computed
      Tomography Myocardial Perfusion.
AB  - PURPOSE OF REVIEW: To review methodological and logistical aspects of CT
      myocardial perfusion, current clinical evidence and possible future directions,
      with specific focus on use in patients with coronary artery disease (CAD). RECENT
      FINDINGS: CT myocardial perfusion imaging may be performed as an add-on to
      standard coronary CT angiography (CCTA), to identify regions of myocardial
      hypoperfusion, at rest and during adenosine stress. The principle of measurement
      is well-validated in animal experimental models, and CT myocardial perfusion
      imaging has a high degree of concordance with already clinically available
      perfusion imaging methods. Combining CCTA and CT myocardial perfusion imaging
      increases the diagnostic accuracy to identify patients with CAD associated with
      ischemia. In patients suspected of CAD, CCTA frequently detects coronary
      atherosclerotic lesions, in which revascularization could be clinically
      beneficial. CT myocardial perfusion imaging may be helpful to identify coronary
      lesions associated with myocardial ischemia, and thus potentially suitable for
      coronary intervention.

PMID- 29071432
TI  - Identification of differentially expressed genes in sunflower (Helianthus annuus)
      leaves and roots under drought stress by RNA sequencing.
AB  - BACKGROUND: Sunflower is recognized as one of the most important oil plants with
      strong tolerance to drought in the world. In order to study the response
      mechanisms of sunflower plants to drought stress, gene expression profiling using
      high throughput sequencing was performed for seedling leaves and roots (sunflower
      inbred line R5) after 24 h of drought stress (15% PEG 6000). The transcriptome
      assembled using sequences of 12 samples was used as a reference. RESULTS: 805 and
      198 genes were identified that were differentially expressed in leaves and roots,
      respectively. Another 71 genes were differentially expressed in both organs, in
      which more genes were up-regulated than down-regulated. In agreement with results
      obtained for other crops or from previous sunflower studies, we also observed
      that nine genes may be associated with the response of sunflower to drought.
      CONCLUSIONS: The results of this study may provide new information regarding the
      sunflower drought response, as well as add to the number of known genes
      associated with drought tolerance.

PMID- 29071433
TI  - Comparison of Different Methods to Identify tdh-Positive Pathogenic Vibrio
      parahaemolyticus Isolates.
AB  - We evaluated the accuracy and ease of operation of three methods to identify tdh
      positive Vibrio parahaemolyticus isolates, including the Kanagawa phenomenon test
      (KP test), a tdh gene PCR test, and a colloidal gold immunochromatographic assay
      (CGIA). A total of 221 V. parahaemolyticus isolates were collected from patients,
      freshly harvested seafood, and fresh seawater. Using the KP test, 92% of V.
      parahaemolyticus isolates from patients were identified tdh-positive, including
      four weak KP-positive isolates. The PCR test and CGIA also identified 92% of the
      isolates as tdh-positive. However, PCR and CGIA only confirmed one of the four
      weak KP-positive isolates. Similar results were obtained using the three methods
      to identify V. parahaemolyticus isolates from the other sources. Among the three
      methods, the KP test was the simplest to perform because it lacked any
      requirement for sample pretreatment, and was low cost, with no equipment
      requirements. Therefore, the KP test has been applied widely in many first-line
      quarantine laboratories. However, the sensitivity and accuracy of KP test were
      lower than those of the other two methods. PCR can identify the tdh rapidly,
      specifically, and sensitively. However, PCR requires equipment and facilities
      that are unavailable in first-line quarantine laboratories. The CGIA can
      compensate for the disadvantages of the other two methods by its higher
      sensitivity, accuracy, and ease of operation. Therefore, the CGIA has the highest
      potential to be used to identify tdh-positive V. parahaemolyticus isolates to
      guarantee food safety.

PMID- 29071434
TI  - Does alignment of the limb and tibial width determine relative narrowing between
      compartments when planning mechanically aligned TKA?
AB  - INTRODUCTION: We determined (1) the range of the hip-knee-ankle (HKA) angle in
      the native or pre-arthritic limbs of patients with a contralateral total knee
      arthroplasty (TKA); and when mechanical alignment is planned (2) the
      relationships between the HKA angle and the tibial width, and the relative
      narrowing between the medial and lateral compartments and (3) the effect of
      tibial width on the range of narrowing. METHODS: The HKA angle, distal lateral
      femoral angle (DLFA), and proximal medial tibial angle (PMTA) were measured on
      the native limb of 102 subjects (53 female) treated with contralateral TKA. The
      sine of the angle of the resection gap (PMTA minus 90 degrees  subtracted from
      the DLFA minus 90 degrees ) multiplied by the tibial width and by narrow (59 mm),
      average (75 mm), and wide (91 mm) tibias computed relative narrowing. RESULTS:
      The HKA angle ranged from 8 degrees  varus to - 7 degrees  valgus; 20% had
      constitutional varus (>= 3 degrees ) and 11% constitutional valgus (<= - 3
      degrees ). The HKA angle strongly predicted (r 2 = 0.87) and tibial width weakly
      predicted (r 2 = 0.06) relative narrowing. For narrow, average, and wide tibias,
      the maximum medial narrowing was 9, 11, 14 mm and maximum lateral narrowing was
      7, 9, and 11 mm, respectively (p < 0.0001). CONCLUSION: When mechanical alignment
      is planned, there is greater relative narrowing between compartments when the pre
      arthritic limb greatly deviates from a 0 degrees  HKA angle and the tibia is
      wide. These limbs may need soft-tissue releases until neutral postoperative limb
      alignment of 0 degrees  and negligible varus-valgus laxity are achieved. LEVEL OF
      EVIDENCE: IV, therapeutic study.

PMID- 29071436
TI  - Measurement and scan reproducibility of parameters of intravoxel incoherent
      motion in renal tumor and normal renal parenchyma: a preliminary research at 3.0
      T MR.
AB  - PURPOSE: To prospectively estimate measurement and scan reproducibility of
      parameters of intravoxel incoherent motion (IVIM) in renal tumors, normal renal
      cortex, and medulla. METHODS: Twenty-four consecutive patients (twelve males and
      twelve females; median age 56.7 years, range 32-71 years) with 25 renal tumors
      (20 renal cell carcinomas, one urothelium carcinoma, three angiomyolipomas, and
      one oncocytoma) were examined twice using IVIM1 and IVIM2 with 9 and 16 b values,
      respectively, at 3.0 T. All the patients were re-scanned in 24-48 h. Regions of
      interest (ROIs) were placed in solid part of tumor, normal cortex, and medulla to
      derive IVIM parameters D (true diffusion coefficient), D* (pseudodiffusion
      coefficient), and f (perfusion fraction of pseudodiffusion). Differences in
      parameters between two IVIM sets and intra-observer, inter-observer, and scan
      rescan differences were assessed using paired t tests. Intra-observer, inter
      observer, and scan-rescan reproducibility were assessed by measuring coefficient
      of variation and Bland-Altman limits of agreements. RESULTS: Intra-observer
      reproducibility of renal tumors, normal renal cortex, and medulla was excellent
      for apparent diffusion coefficient (ADC; CV: 3.45%-5.34%, BA-LA: -14% to 18%) and
      D (CV: 3.65% to 6.04%, BA-LA: -18% to 19%), good for f (CV: 11.96%-16.08%, BA-LA:
      -76.4% to 92.1% except f of medulla with CV of 32.59% and BA-LA of -76.4% to
      92.1% in IVIM1), and poor for D* (CV: 25.0% to 75.4%, BA-LA: -111% to 150%). The
      same order was in inter-observer reproducibility analysis. Scan-rescan
      reproducibility was the worst of the three parameters. Renal medulla showed worse
      reproducibility than renal tumors and the normal cortex. The metrics of IVIM2 had
      better reproducibility than IVIM1. CONCLUSION: Excellent reproducibility
      evaluation for ADC and D, good for f, and poor for D* derived from IVIM was
      performed in renal tumors, normal renal cortex, and medulla. D* has limited
      reliability and scan-rescan reproducibility should be improved.

PMID- 29071435
TI  - The Effect of Xanthine Oxidase Inhibitors on Blood Pressure and Renal Function.
AB  - Several epidemiological studies have demonstrated the existence of a correlation
      between high serum uric acid (SUA) levels, hypertension, and chronic kidney
      disease (CKD). Xantine oxidase inhibitors (XOI) are the most powerful uric acid
      lowering drugs, with presumed beneficial effects on cardiovascular and renal
      system. The multifactorial mechanism linking hyperuricemia with cardiovascular
      and renal diseases involves both the SUA level and the xanthine oxidase (XO)
      activity. In this context, the clinical research has been recently focused at
      assessing the efficacy of urate-lowering drugs active on XO in patients with
      abnormal blood pressure values and renal dysfunction. The mechanism of action
      responsible for the beneficial effect of XOI has not completely elucidated, and
      long-term studies involving large population samples are needed. In particular,
      XOI could play an important role in the management of hypertension and CKD,
      especially in patients not entirely controlled by conventional therapies. In the
      present review, we summarize the results of recent clinical trials that largely
      support a positive effect of allopurinol and febuxostat on blood pressure,
      glomerular filtration rate (GFR), and serum creatinine in different populations
      of patients. Will these drugs be considered a reliable choice or alternative to
      currently used drugs for the hypertension and kidney failure treatment? The
      debate is open, but much evidence is accumulating and supporting this role.

PMID- 29071437
TI  - Effect of long-term remote ischemic conditioning in patients with chronic
      ischemic heart failure.
AB  - Remote ischemic conditioning (RIC) protects against acute ischemia-reperfusion
      injury and may also have beneficial effects in patients with stable
      cardiovascular disease. We investigated the effect of long-term RIC treatment in
      patients with chronic ischaemic heart failure (CIHF). In a parallel group study,
      22 patients with compensated CIHF and 21 matched control subjects without heart
      failure or ischemic heart disease were evaluated by cardiac magnetic resonance
      imaging, cardiopulmonary exercise testing, skeletal muscle function testing,
      blood pressure measurement and blood sampling before and after 28 +/- 4 days of
      once daily RIC treatment. RIC was conducted as four cycles of 5 min upper arm
      ischemia followed by 5 min of reperfusion. RIC did not affect left ventricular
      ejection fraction (LVEF) or global longitudinal strain (GLS) in patients with
      CIHF (p = 0.63 and p = 0.11) or matched controls (p = 0.32 and p = 0.20). RIC
      improved GLS in the subgroup of patients with CIHF and with NT-proBNP plasma
      levels above the geometric mean of 372 ng/l (p = 0.04). RIC did not affect peak
      workload or oxygen uptake in either patients with CIHF (p = 0.26 and p = 0.59) or
      matched controls (p = 0.61 and p = 0.10). However, RIC improved skeletal muscle
      power in both groups (p = 0.02 for both). In patients with CIHF, RIC lowered
      systolic blood pressure (p < 0.01) and reduced NT-proBNP plasma levels (p =
      0.02). Our findings suggest that long-term RIC treatment does not improve LVEF
      but increases skeletal muscle function and reduces blood pressure and NT-proBNP
      in patients with compensated CIHF. This should be investigated in a randomized
      sham-controlled trial.

PMID- 29071438
TI  - Predictive value of dysregulation profile trajectories in childhood for symptoms
      of ADHD, anxiety and depression in late adolescence.
AB  - We examined whether there are certain dysregulation profile trajectories in
      childhood that may predict an elevated risk for mental disorders in later
      adolescence. Participants (N = 554) were drawn from a representative community
      sample of German children, 7-11 years old, who were followed over four
      measurement points (baseline, 1, 2 and 6 years later). Dysregulation profile,
      derived from the parent report of the Strengths and Difficulties Questionnaire,
      was measured at the first three measurement points, while symptoms of attention
      deficit hyperactivity disorder (ADHD), anxiety and depression were assessed at
      the fourth measurement point. We used latent class growth analysis to investigate
      developmental trajectories in the development of the dysregulation profile. The
      predictive value of dysregulation profile trajectories for later ADHD, anxiety
      and depression was examined by linear regression. For descriptive comparison, the
      predictive value of a single measurement (baseline) was calculated. Dysregulation
      profile was a stable trait during childhood. Boys and girls had similar levels of
      dysregulation profile over time. Two developmental subgroups were identified,
      namely the low dysregulation profile and the high dysregulation profile
      trajectory. The group membership in the high dysregulation profile trajectory (n
      = 102) was best predictive of later ADHD, regardless of an individual's gender
      and age. It explained 11% of the behavioural variance. For anxiety this was 8.7%
      and for depression 5.6%, including some gender effects. The single-point
      measurement was less predictive. An enduring high dysregulation profile in
      childhood showed some predictive value for psychological functioning 4 years
      later. Hence, it might be helpful in the preventive monitoring of children at
      risk.

PMID- 29071439
TI  - Cognition is associated with gait variability in individuals with multiple
      sclerosis.
AB  - Fluctuations in gait, or gait variability, are closely related to cognitive
      function in various clinical populations. However, there are limited data on this
      relationship in multiple sclerosis (MS) patients. This investigation determined
      whether cognitive function as measured by processing speed is associated with
      gait variability in individuals with MS. This secondary analysis included 191
      individuals with MS who underwent gait assessment and cognitive assessment.
      Cognitive processing speed was index by symbol digit modalities test (SDMT). Gait
      variability was indexed by step length and step time coefficient of variation
      (CV). Hierarchical linear regressions were performed to examine whether SDMT
      scores would predict step length and step time CV. After adjusting for age,
      gender, and disability, we found that SDMT was a significant predictor of step
      time CV (p < 0.001) and step length CV (p = 0.03). Overall, slower cognitive
      processing speed was significantly associated with greater gait variability. It
      is speculated that neural damage in MS patients impairs both cognitive processing
      speed and gait control. This study provides further evidence that motor and
      cognitive functions are interrelated.

PMID- 29071440
TI  - Reduction of the relative centrifugal force influences cell number and growth
      factor release within injectable PRF-based matrices.
AB  - Platelet rich fibrin (PRF) is a blood concentrate system obtained by
      centrifugation of peripheral blood. First PRF matrices exhibited solid fibrin
      scaffold, more recently liquid PRF-based matrix was developed by reducing the
      relative centrifugation force and time. The aim of this study was to
      systematically evaluate the influence of RCF (relative centrifugal force) on cell
      types and growth factor release within injectable PRF- in the range of 60-966 g
      using consistent centrifugation time. Numbers of cells was analyzed using
      automated cell counting (platelets, leukocytes, neutrophils, lymphocytes and
      monocytes) and histomorphometrically (CD 61, CD- 45, CD-15+, CD-68+, CD-3+ and CD
      20). ELISA was utilized to quantify the concentration of growth factors and
      cytokines including PDGF-BB, TGF-beta1, EGF, VEGF and MMP-9. Leukocytes,
      neutrophils, monocytes and lymphocytes had significantly higher total cell
      numbers using lower RCF. Whereas, platelets in the low and medium RCF ranges both
      demonstrated significantly higher values when compared to the high RCF group.
      Histomorphometrical analysis showed a significantly high number of CD61+, CD-45+
      and CD-15+ cells in the low RCF group whereas CD-68+, CD-3+ and CD-20+
      demonstrated no statistically significant differences between all groups. Total
      growth factor release of PDGF-BB, TGF-beta1 and EGF had similar values using low
      and medium RCF, which were both significantly higher than those in the high RCF
      group. VEGF and MMP-9 were significantly higher in the low RCF group compared to
      high RCF. These findings support the LSCC (low speed centrifugation concept),
      which confirms that improved PRF-based matrices may be generated through RCF
      reduction. The enhanced regenerative potential of PRF-based matrices makes them a
      potential source to serve as a natural drug delivery system. However, further pre
      clinical and clinical studies are required to evaluate the regeneration capacity
      of this system.

PMID- 29071441
TI  - Kinetic characterization of the inhibition of protein tyrosine phosphatase-1B by
      Vanadyl (VO2+) chelates.
AB  - Protein tyrosine phosphatases (PTPases) are a prominent focus of drug design
      studies because of their roles in homeostasis and disorders of metabolism. These
      studies have met with little success because (1) virtually all inhibitors
      hitherto exhibit only competitive behavior and (2) a consensus sequence H/V-C-X5
      R-S/T characterizes the active sites of PTPases, leading to low specificity of
      active site directed inhibitors. With protein tyrosine phosphatase-1B (PTP1B)
      identifed as the target enzyme of the vanadyl (VO2+) chelate
      bis(acetylacetonato)oxidovanadium(IV) [VO(acac)2] in 3T3-L1 adipocytes [Ou et al.
      J Biol Inorg Chem 10: 874-886, 2005], we compared the inhibition of PTP1B by
      VO(acac)2 with other VO2+-chelates, namely, bis(2-ethyl
      maltolato)oxidovanadium(IV) [VO(Et-malto)2] and bis(3-hydroxy-2-methyl
      4(1H)pyridinonato)oxidovanadium(IV) [VO(mpp)2] under steady-state conditions,
      using the soluble portion of the recombinant human enzyme (residues 1-321). Our
      results differed from those of previous investigations because we compared
      inhibition in the presence of the nonspecific substrate p-nitrophenylphosphate
      and the phosphotyrosine-containing undecapeptide DADEpYLIPQQG mimicking residues
      988-998 of the epidermal growth factor receptor, a relevant, natural substrate.
      While VO(Et-malto)2 acts only as a noncompetitive inhibitor in the presence of
      either subtrate, VO(acac)2 exhibits classical uncompetitive inhibition in the
      presence of DADEpYLIPQQG but only apparent competitive inhibition with p
      nitrophenylphosphate as substrate. Because uncompetitive inhibitors are more
      potent pharmacologically than competitive inhibitors, structural characterization
      of the site of uncompetitive binding of VO(acac)2 may provide a new direction for
      design of inhibitors for therapeutic purposes. Our results suggest also that the
      true behavior of other inhibitors may have been masked when assayed with only p
      nitrophenylphosphate as substrate.

PMID- 29071442
TI  - Development of multifunctional nanoparticles towards applications in non-invasive
      magnetic resonance imaging and axonal tracing.
AB  - A multifunctional nanobiomaterial has been developed by deliberately combining
      functions of superparamagnetism, fluorescence, and axonal tracing into one
      material. Superparamagnetic iron oxide nanoparticles were first synthesized and
      coated with a silica layer to prevent emission quenching through core-dye
      interactions; a fluorescent molecule, fluorescein isothiocyanate, was doped
      inside second layer of silica shell to improve photo-stability and to enable
      further thiol functionalization. Subsequently, biotinylated dextran amine, a
      sensitive axonal tracing reagent, was immobilized on the thiol-functionalized
      nanoparticle surfaces. The resulting nanoparticles were characterized by
      transmission electron microscopy, dynamic light scattering, X-ray diffraction, X
      ray photoelectron spectroscopy, UV-Vis spectroscopy, magnetic resonance imaging
      and fluorescence confocal microscopy. In vitro cell experiments using both
      undifferentiated and differentiated Neuro-2a cells showed that the cells were
      able to take up the nanoparticles intracellularly and that the nanoparticles
      showed good biocompatibilities. In summary, this new material demonstrated
      promising performances for both optical and magnetic resonance imaging
      modalities, suggesting its promising potentials in applications such as in non
      invasive imaging, particularly in neuronal tracing.

PMID- 29071443
TI  - Assessment of the effectiveness of cyclosporine nasal spray in an animal model of
      allergic rhinitis.
AB  - The aim of this study is to show if cyclosporine has an antiallergic role in a
      rat model of ovalbumin-induced allergic rhinitis. The 54 rats were divided into
      six equal groups. The first group was a negative control group without induced
      allergic rhinitis; the second group a positive control with induced allergic
      rhinitis not receiving treatment. The remaining four groups, after induction of
      allergic rhinitis, received intranasal cyclosporine treatment in doses of 0.05,
      0.1, or 0.2% or nasal steroid treatment. In the biochemical examination, on the
      surface of the tissue tumor necrosis factor (TNF) interferon (IFN), interleukin
      (IL)-5, IL-13, as well as IL-2, IL-4, IL-17A, and IgE were studied.
      Histologically, ciliary loss, increase of goblet cells, vascular congestion, and
      the degree of eosinophil infiltration were rated. In all treatment groups, on
      average, a significant reduction in all histological and biochemical values was
      found compared to the positive control group. Comparing each of the three
      cyclosporine-using groups with the group of nasal corticosteroid did not show any
      significant difference in the average scores. Cyclosporine nasal drops are
      effective to be used in an animal model of experimental allergic rhinitis without
      systemic effects.

PMID- 29071445
TI  - Ultrafast structural molecular dynamics investigated with 2D infrared
      spectroscopy methods.
AB  - Ultrafast, multi-dimensional infrared (IR) spectroscopy has been advanced in
      recent years to a versatile analytical tool with a broad range of applications to
      elucidate molecular structure on ultrafast timescales, and it can be used for
      samples in a many different environments. Following a short and general
      introduction on the benefits of 2D IR spectroscopy, the first part of this
      chapter contains a brief discussion on basic descriptions and conceptual
      considerations of 2D IR spectroscopy. Outstanding classical applications of 2D IR
      are used afterwards to highlight the strengths and basic applicability of the
      method. This includes the identification of vibrational coupling in molecules,
      characterization of spectral diffusion dynamics, chemical exchange of chemical
      bond formation and breaking, as well as dynamics of intra- and intermolecular
      energy transfer for molecules in bulk solution and thin films. In the second
      part, several important, recently developed variants and new applications of 2D
      IR spectroscopy are introduced. These methods focus on (i) applications to
      molecules under two- and three-dimensional confinement, (ii) the combination of
      2D IR with electrochemistry, (iii) ultrafast 2D IR in conjunction with
      diffraction-limited microscopy, (iv) several variants of non-equilibrium 2D IR
      spectroscopy such as transient 2D IR and 3D IR, and (v) extensions of the pump
      and probe spectral regions for multi-dimensional vibrational spectroscopy towards
      mixed vibrational-electronic spectroscopies. In light of these examples, the
      important open scientific and conceptual questions with regard to intra- and
      intermolecular dynamics are highlighted. Such questions can be tackled with the
      existing arsenal of experimental variants of 2D IR spectroscopy to promote the
      understanding of fundamentally new aspects in chemistry, biology and materials
      science. The final part of the chapter introduces several concepts of currently
      performed technical developments, which aim at exploiting 2D IR spectroscopy as
      an analytical tool. Such developments embrace the combination of 2D IR
      spectroscopy and plasmonic spectroscopy for ultrasensitive analytics, merging 2D
      IR spectroscopy with ultra-high-resolution microscopy (nanoscopy), future
      variants of transient 2D IR methods, or 2D IR in conjunction with microfluidics.
      It is expected that these techniques will allow for groundbreaking research in
      many new areas of natural sciences.

PMID- 29071444
TI  - Multivariate analysis of prognostic factors for idiopathic sudden sensorineural
      hearing loss treated with adjuvant hyperbaric oxygen therapy.
AB  - The objective of this study is to evaluate possible prognostic factors of
      idiopathic sudden sensorineural hearing loss (ISSNHL) treated with adjuvant
      hyperbaric oxygen therapy (HBOT) using univariate and multivariate analyses. From
      January 2008 to October 2016, records of 178 ISSNHL patients treated with
      auxiliary hyperbaric oxygen therapy were reviewed to assess hearing recovery and
      evaluate associated prognostic factors (gender, age, localization, initial
      hearing threshold, presence of tinnitus, vertigo, ear fullness, hypertension,
      diabetes, onset of HBOT, number of HBOT, and audiogram), by using univariate and
      multivariate analyses. The overall recovery rate was 37.1%, including complete
      recovery (19.7%) and partial recovery (17.4%). According to multivariate
      analysis, later onset of HBOT and higher initial hearing threshold were
      associated with a poor prognosis in ISSNHL patients treated with HBOT. HBOT is a
      safe and beneficial adjuvant therapy for ISSNHL patients. 20 sessions of HBOT is
      possibly enough to show its therapeutic effect. Earlier HBOT onset and lower
      initial hearing threshold is associated with favorable hearing recovery.

PMID- 29071446
TI  - Sequence requirement of the ade6-4095 meiotic recombination hotspot in
      Schizosaccharomyces pombe.
AB  - Homologous recombination occurs at a greatly elevated frequency in meiosis
      compared to mitosis and is initiated by programmed double-strand DNA breaks
      (DSBs). DSBs do not occur at uniform frequency throughout the genome in most
      organisms, but occur preferentially at a limited number of sites referred to as
      hotspots. The location of hotspots have been determined at nucleotide-level
      resolution in both the budding and fission yeasts, and while several patterns
      have emerged regarding preferred locations for DSB hotspots, it remains unclear
      why particular sites experience DSBs at much higher frequency than other sites
      with seemingly similar properties. Short sequence motifs, which are often sites
      for binding of transcription factors, are known to be responsible for a number of
      hotspots. In this study we identified the minimum sequence required for activity
      of one of such motif identified in a screen of random sequences capable of
      producing recombination hotspots. The experimentally determined sequence,
      GGTCTRGACC, closely matches the previously inferred sequence. Full hotspot
      activity requires an effective sequence length of 9.5 bp, whereas moderate
      activity requires an effective sequence length of approximately 8.2 bp and shows
      significant association with DSB hotspots. In combination with our previous work,
      this result is consistent with a large number of different sequence motifs
      capable of producing recombination hotspots, and supports a model in which
      hotspots can be rapidly regenerated by mutation as they are lost through
      recombination.

PMID- 29071447
TI  - Scanning electron microscope imaging of pilonidal disease.

PMID- 29071449
TI  - Preliminary studies on haematological and plasmatic parameters in gilthead sea
      bream (Sparus aurata) held under day/night temperature variations.
AB  - This study aimed to evaluate to what extent diel water temperature oscillations
      over a short period of time (41 h) affected haematologic and plasmatic parameters
      of gilthead sea bream. Sea bream juveniles (160 fish; 177.2 +/- 20.9 g) were
      divided in two homogenous groups, experimental and control. The experimental
      group was exposed to water at 22.3 +/- 0.6  degrees C between 5 a.m. and 5 p.m.
      and to colder water from 5 p.m. to 5 a.m. (temperature variation of 8.6 +/- 0.3 
      degrees C) during 41h period, whereas for the control group, water temperature
      was maintained constant (22.4 +/- 0.7  degrees C) for the same period. Fish were
      fed three times per day (10:30 a.m., 2 p.m., 4 p.m.). Blood was collected from
      fish caudal veins (n = 6) at different time points (10 a.m., 1 p.m., 5 p.m., 6:30
      p.m., 8 p.m. and 10 a.m. of the following day) from each group, for haematologic
      (haematocrit and haemoglobin) and plasmatic (glucose, cortisol, triglycerides and
      total protein) determinations. All parameters studied tended to vary throughout
      the study period, both for experimental and control groups. Significant
      differences were observed between the two groups for all the studied parameters
      at different sampling points. These differences were observed near the influence
      of the cold-water period or during the cooling-water period. Results suggested
      that colder water temperature cycles depressed fish metabolic activity and
      affected the levels of the analysed blood-circulating metabolites. Overall,
      results suggested that stress response was similar for experimental and control
      groups and that gilthead sea bream were able to cope with diel water temperature
      variations.

PMID- 29071450
TI  - Parasitoid wasps' exposure to host-infested plant volatiles affects their
      olfactory cognition of host-infested plants.
AB  - Using Cotesia vestalis, a parasitoid wasp of diamondback moth larvae and three
      crucifer plant species (cabbage, komatsuna, and Japanese radish), we examined the
      effects of exposure to host-infested plant volatiles from one plant species on a
      newly emerged wasp's subsequent olfactory cognition of host-infested plant
      volatiles from the same or different plant species. The preference of C. vestalis
      between infested and uninfested plant volatiles was tested in a choice chamber.
      Volatile-inexperienced wasps significantly preferred infested cabbage and
      infested radish volatiles, but not infested komatsuna volatiles. After exposure
      to infested cabbage volatiles, wasps showed a significant preference for infested
      cabbage volatiles, while the significant preference for infested radish volatiles
      that had been observed in inexperienced wasps was no longer observed. After
      exposure to infested komatsuna volatiles, wasps significantly preferred infested
      komatsuna volatiles, and the pre-exposure significant preferences for infested
      cabbage volatiles and infested radish volatiles remained. After exposure to
      infested radish volatiles, the significant preferences for infested cabbage and
      infested radish volatiles did not change. Furthermore, wasps showed a significant
      preference for infested komatsuna volatiles. The compound compositions of the
      volatile blends from the three infested plant species were grouped separately in
      a principal coordinates analysis. The experience-based cognition of C. vestalis
      for host-infested plant volatiles of three plant species is discussed.

PMID- 29071448
TI  - Effects of acute handling stress on short-term central expression of
      orexigenic/anorexigenic genes in zebrafish.
AB  - Physiological mechanisms driving stress response in vertebrates are
      evolutionarily conserved. These mechanisms involve the activation of both the
      hypothalamic-sympathetic-chromaffin cell (HSC) and the hypothalamic-pituitary
      adrenal (HPA) axes. In fish, the reduction of food intake levels is a common
      feature of the behavioral response to stress but the central mechanisms
      coordinating the energetic response are not well understood yet. In this work, we
      explore the effects of acute stress on key central systems regulating food intake
      in fish as well as on total body cortisol and glucose levels. We show that acute
      stress induced a rapid increase in total body cortisol with no changes in body
      glucose, at the same time promoting a prompt central response by activating
      neuronal pathways. All three orexigenic peptides examined, i.e., neuropeptide y
      (npy), agouti-related protein (agrp), and ghrelin, increased their central
      expression level suggesting that these neuronal systems are not involved in the
      short-term feeding inhibitory effects of acute stress. By contrast, the
      anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased
      expression after acute stress, suggesting their involvement in the anorexigenic
      effects.

PMID- 29071451
TI  - Effect of antimicrobial photodynamic therapy (aPDT) on the sterilization of
      infected dentin in vitro.
AB  - The aim of this study was to evaluate the bactericidal effect of antimicrobial
      photodynamic therapy (aPDT) on an infected dentin model. Dentin plates were
      prepared from extracted human molars and infected through immersion in a solution
      of Streptococcus mutans. The nine experimental groups consisted of two laser
      irradiation groups (650 nm laser: 650 laser and 940 nm laser: 940 laser), two
      photosensitizer groups (methylene blue: MB, and azulenocyanine: Azc), four aPDT
      groups (650 nm laser irradiation of MB: 650 laser-MB, 650 nm laser irradiation of
      Azc: 650 laser-Azc, 940 nm laser irradiation of MB: 940 laser-MB and 940 nm laser
      irradiation of Azc: 940 laser-Azc) and a control. The bactericidal effects on
      each group were evaluated by colony count and adenosine triphosphate (ATP)
      assays. Based on the results of the colony count assay, the 650 laser-MB and 940
      laser-MB groups formed significantly fewer colonies than the other experimental
      groups. Significantly fewer colonies were observed in the 940 laser-Azc group
      than in the control, but significant differences in the numbers of colonies were
      not observed between the 650 laser-Azc and control groups. The 940 laser group
      formed slightly fewer colonies than the 650 laser group, but the difference was
      not significant. In addition, the number of colonies in the MB group was
      significantly less than the number in the Azc group. The results of the ATP assay
      were similar to those of the colony count assay. aPDT with MB showed a
      significant bactericidal effect on dentin plates infected with S. mutans.

PMID- 29071452
TI  - Health risk assessment of heavy metal intake due to fish consumption in the
      Sistan region, Iran.
AB  - The heavy metal (Pb, Cd, Cr, and Ni) content of a fish species consumed by the
      Sistan population and its associated health risk factors were investigated. The
      mean concentrations of Pb, Cd, and Cr were slightly higher than the standard
      levels. The Ni content of fish was below the maximum guideline proposed by the US
      Food and Drug Administration (USFDA). The average estimated weekly intake was
      significantly below the provisional tolerable intake based on the FAO and WHO
      standards for all studied metals. The target hazard quotients (THQ) of all metals
      were below 1, showing an absence of health hazard for the population of Sistan.
      The combined target hazard quotient for the considered metals was 26.94 * 10-3.
      The cancer risk factor for Pb (1.57 * 10-7) was below the acceptable lifetime
      carcinogenic risk (10-5). The results of this study reveal an almost safe level
      of Pb, Cd, Cr, and Ni contents in the fish consumed by the Sistan population.
      Graphical abstract ?.

PMID- 29071453
TI  - Donor cornea tissue in cases of drowning or water submersion: eye banks practice
      patterns and tissue outcomes.
AB  - Surgical use of donor corneal tissue from victims of water submersion (drowning
      or submersion secondary to death) remains controversial due to limited evidence
      about the quality of these tissues. To assess the safety of donor corneal tissue
      from victims of water submersion, an investigation of eye banks' practice
      patterns and tissue outcomes was conducted. All 79 Eye Bank Association of
      America accredited eye banks were contacted for a phone interview of practices
      regarding tissue from victims of water submersion. A retrospective review of
      corneal tissues from 2014 to 2016 from a large eye bank network was performed to
      identify all donors submerged in water. Corneal epithelial integrity, endothelial
      cell density (ECD), rim cultures, and adverse events were analyzed for
      associations with water submersion characteristics. 49 eye banks (62% response)
      participated in the survey. 55% of these eye banks had specific, written protocol
      for tissue eligibility from donors submerged in water. With or without specific
      protocol, eye banks reported considering water type (84%) and length of time
      submerged (92%) to determine eligibility. 22% of eye banks reported medical
      director involvement when eligibility determination was unclear. 79 tissues from
      40 donors who were submerged were identified in 2014-2016 eye bank data. No donor
      tissues had pre-processing corneal infiltrates, positive rim cultures, or adverse
      events post-keratoplasty. Corneal epithelial integrity and ECD were not
      associated with water type or length of time submerged. In conclusion, data from
      a large eye bank network showed no adverse events or outcomes, indicating these
      tissues may be safe.

PMID- 29071454
TI  - What Is the Role of Oral Prostacyclin Pathway Medications in Pulmonary Arterial
      Hypertension Management?
AB  - PURPOSE OF REVIEW: Prostacyclin pathway medications have been shown to be highly
      efficacious in the treatment of pulmonary arterial hypertension (PAH) through
      multiple prospective clinical trials and more than two decades of clinical
      experience. The strongest support for prostacyclin use in PAH management is with
      parenteral administration. Numerous risks and limitations of parenteral delivery
      systems as well as significant patient burdens restrict widespread parenteral
      use. Highly effective and tolerable oral prostacyclin preparations to manage PAH
      have long been sought. We review the development of the oral prostacyclin agents
      beraprost, treprostinil, and selexipag and including current indications and
      limitations. Research into new approaches to the management of PAH, expanding
      indications for existing agents, and development of novel agents are also
      discussed. RECENT FINDINGS: Two oral prostacyclin pathway medications, oral
      treprostinil and selexipag, were FDA approved in December 2013 and 2015,
      respectively. Current guidelines recommend use of selexipag in WHO-FC II and III
      (class 1, level B recommendation) and oral treprostinil in WHO-FC III (class 2b,
      level B recommendation). The use of these medications is challenging due to
      complexity in dosing and their side effect profiles which limit patient
      tolerability and acceptance. There is a promising role for oral prostacyclin
      pathway medications in patients with PAH. Future investigations are underway of
      alternative dose regimens and transitioning from parenteral therapies in order to
      improve efficacy and tolerability.

PMID- 29071455
TI  - Assessment of significant psychological distress at the end of pregnancy and
      associated factors.
AB  - The aim of this study is to study the prevalence of mental distress at the end of
      pregnancy and after birth and the impact of selected socio-demographic and
      obstetric factors. This is a cross-sectional study. The sample is consisted of
      351 puerperal women at the age of 18 and over. Sociodemographic, obstetric
      variables were collected to detect significant psychological distress; the
      instrument used was General Health Questionnaire (GHQ-28). Logistic multivariable
      regressions were used to investigate associations. The prevalence of significant
      mental distress amounted to 81.2%, mostly related to social relationship and
      anxiety. The women who affirmed having more stress during pregnancy had too
      significantly increased emotional distress before the birth as well as during
      early puerperium, increasing somatic symptoms (p < 0.001; OR 2.685; CI 95% 1.583
      4.553), anxiety (p < 0.001; OR 4.676; CI 95% 2.846-7.684), and depressive
      symptoms (p < 0.01). Somatic symptoms (p < 0.05; OR 2.466; CI 95% 1.100-5.528)
      and social dysfunction (p < 0.001; OR 1.672; CI 95% 0.711-3.932) occur most
      frequently in women who already had children. Regarding socio-demographic data,
      being an immigrant is the only protective factor reducing the social dysfunction
      in the last weeks of pregnancy (p < 0.01; OR 0.478; CI 95% 0.274-0.832).
      Psychological distress at the end of a full-term pregnancy and in the postpartum
      period occurs frequently and was associated mainly with stress experienced during
      pregnancy and parity. It is advisable to perform proper assessment of stress and
      significant psychological distress at the early stage of pregnancy and repeatedly
      later on until delivery. Information and support from professionals can help to
      decrease and prevent their negative impact on maternal and fetal health, as
      observed in the current evidence.

PMID- 29071456
TI  - Regional Distribution of Longevity Population and Elements in Drinking Water in
      Jiangjin District, Chongqing City, China.
AB  - In order to determine the spatial variation of longevity population and elements
      contained in the drinking water of longevity region in Jiangjin and investigate
      the relationship between the elements in drinking water and longevity, population
      censuses on township level and 98 drinking water samples from Jiangjin District,
      Chongqing City in West China were collected and analyzed. Population statistics
      on township level showed that the number of centenarians per 100,000 inhabitants
      (OC), centenarity index (CI), and number of centenarians per 10,000 over 65-year
      old subjects (UC) present obvious geographic distribution properties, generally
      Central region > Northern region > Southern region (Kruskal-Wallis test, p <
      0.05). Moderate hard water (150 mg/L < total hardness (TH) = 156.17 mg/L < 300
      mg/L) was mainly found in drinking water from longevity township (OC > 7.5) in
      Jiangjin District, whereas soft water (75 mg/L < TH = 111.23 mg/L < 150 mg/L) was
      mostly in non-longevity township (OC < 7.5). The mean concentration of strontium
      (Sr) (0.73 mg/L) in drinking water from the longevity township was apparently
      higher than that of non-longevity township (0.44 mg/L) (Mann-Whitney U test, p =
      0.019 < 0.05). The concentrations of Ba, Li, Mn, Ni, and Se in drinking water
      from longevity township were also higher than those of non-longevity township
      (Mann-Whitney U test, p < 0.05). The research indicates that exercising strict
      control over the concentrations of TH, Sr, Ba, Li, Mn, Ni, and Se in drinking
      water might be good for the health and prolong people's life.

PMID- 29071458
TI  - Species Identification of Fox-, Mink-, Dog-, and Rabbit-Derived Ingredients by
      Multiplex PCR and Real-Time PCR Assay.
AB  - Various detection methods have been developed to date for identification of
      animal species. New techniques based on PCR approach have raised the hope of
      developing better identification methods, which can overcome the limitations of
      the existing methods. PCR-based methods used the mitochondrial DNA (mtDNA) as
      well as nuclear DNA sequences. In this study, by targeting nuclear DNA, multiplex
      PCR and real-time PCR methods were developed to assist with qualitative and
      quantitative analysis. The multiplex PCR was found to simultaneously and
      effectively distinguish four species (fox, dog, mink, and rabbit) ingredients by
      the different sizes of electrophoretic bands: 480, 317, 220, and 209 bp. Real
      time fluorescent PCR's amplification profiles and standard curves showed good
      quantitative measurement responses and linearity, as indicated by good
      repeatability and coefficient of determination R 2 > 0.99. The quantitative
      results of quaternary DNA mixtures including mink, fox, dog, and rabbit DNA are
      in line with our expectations: R.D. (relative deviation) varied between 1.98 and
      12.23% and R.S.D. (relative standard deviation) varied between 3.06 and 11.51%,
      both of which are well within the acceptance criterion of <= 25%. Combining the
      two methods is suitable for the rapid identification and accurate quantification
      of fox-, dog-, mink-, and rabbit-derived ingredients in the animal products.

PMID- 29071459
TI  - Chemo-Enzymatic Epoxidation of Lallemantia IbericaSeed Oil: Process Development
      and Economic-Ecological Evaluation.
AB  - The chemo-enzymatic epoxidation of Lallemantia iberica seed oil (LISO), a novel
      plant oil characterized by its exceptional high content of alpha-linolenic acid
      (> 60%), was developed using an immobilized lipase from Pseudozyma antarctica and
      hydrogen peroxide as oxidant. A statistical approach was used to study the effect
      of enzyme amount, temperature, time, and solvent amount on the oxirane oxygen
      content obtained during epoxidation. An oxirane oxygen content of 8.6 +/- 0.2%
      corresponding to a yield of 82% was obtained under optimized conditions that were
      identified to be at an enzyme load of 8.2 g/mol of double bonds, a solvent amount
      of 56.4 wt.%, a temperature of 33  degrees C, and an incubation time of 17 h. In
      addition, the experimental investigation was combined with a techno-economic and
      ecological assessment gaining detailed information regarding cost structure and
      environmental impact for the chemo-enzymatic epoxidation of the novel plant oil.

PMID- 29071457
TI  - Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid
      receptor agonist in mouse models of acute, tonic, and chemotherapy-induced
      neuropathic pain.
AB  - BACKGROUND: Cebranopadol (a.k.a. GRT-6005) is a dually acting nociceptin/orphanin
      FQ and opioid receptor agonist that has been recently developed in Phase 2
      clinical trials for painful diabetic neuropathy or cancer pain. It also showed
      analgesic properties in various rat models of pain and had a better safety
      profile as compared to equi-analgesic doses of morphine. Since antinociceptive
      properties of cebranopadol have been studied mainly in rat models, in the present
      study, we assessed analgesic activity of subcutaneous cebranopadol (10 mg/kg) in
      various mouse pain models. METHODS: We used models of acute, tonic, and chronic
      pain induced by thermal and chemical stimuli, with a particular emphasis on
      pharmacoresistant chronic neuropathic pain evoked by oxaliplatin in which
      cebranopadol was used alone or in combination with simvastatin. KEY RESULTS: As
      shown in the hot plate test, the analgesic activity of cebranopadol developed
      more slowly as compared to morphine (90-120 min vs. 60 min). Cebranopadol
      displayed a significant antinociceptive activity in acute pain models, i.e., the
      hot plate, writhing, and capsaicin tests. It attenuated nocifensive responses in
      both phases of the formalin test and reduced cold allodynia in oxaliplatin
      induced neuropathic pain model. Its efficacy was similar to that of morphine.
      Used in combination and administered simultaneously, 4 or 6 h after simvastatin,
      cebranopadol did not potentiate antiallodynic activity of this cholesterol
      lowering drug. Cebranopadol did not induce any motor deficits in the rotarod
      test. CONCLUSION: Cebranopadol may have significant potential for the treatment
      of various pain types, including inflammatory and chemotherapy-induced
      neuropathic pain.

PMID- 29071460
TI  - Triple resonance 15Nu NMR relaxation experiments for studies of intrinsically
      disordered proteins.
AB  - Description of protein dynamics is known to be essential in understanding their
      function. Studies based on a well established [Formula: see text] NMR relaxation
      methodology have been applied to a large number of systems. However, the low
      dispersion of [Formula: see text] chemical shifts very often observed within
      intrinsically disordered proteins complicates utilization of standard 2D HN
      correlated spectra because a limited number of amino acids can be characterized.
      Here we present a suite of triple resonance HNCO-type NMR experiments for
      measurements of five [Formula: see text] relaxation parameters ([Formula: see
      text], [Formula: see text], NOE, cross-correlated relaxation rates [Formula: see
      text] and [Formula: see text]) in doubly [Formula: see text],[Formula: see text]
      labeled proteins. We show that the third spectral dimension combined with non
      uniform sampling provides relaxation rates for almost all residues of a protein
      with extremely poor chemical shift dispersion, the C terminal domain of [Formula:
      see text]-subunit of RNA polymerase from Bacillus subtilis. Comparison with data
      obtained using a sample labeled by [Formula: see text] only showed that the
      presence of [Formula: see text] has a negligible effect on [Formula: see text],
      [Formula: see text], and on the cross-relaxation rate (calculated from NOE and
      [Formula: see text]), and that these relaxation rates can be used to calculate
      accurate spectral density values. Partially [Formula: see text]-labeled sample
      was used to test if the observed increase of [Formula: see text] [Formula: see
      text] in the presence of [Formula: see text] corresponds to the [Formula: see
      text] dipole-dipole interactions in the [Formula: see text],[Formula: see text]
      labeled sample.

PMID- 29071466
TI  - Cardiovascular autonomic effects of vagus nerve stimulation.
AB  - The vagus nerve is responsible for the parasympathetic innervation of the major
      thoracic and abdominal organs. It also carries sensory afferent fibres from these
      viscera and reaches different brain structures. These connections have proven
      useful in the treatment of different diseases. Afferent stimulation of the left
      vagus nerve is used to treat epilepsy and major depression, and stimulation of
      the right vagus nerve is being tried for the treatment of heart failure. The
      device used for the therapy delivers intermittent stimuli. It is indicated
      worldwide for the treatment of drug-resistant epilepsy in patients who are not
      appropriate candidates for respective surgery. It has also received approval for
      the treatment of major depression, obesity and episodic cluster headache by the
      Food and Drug Administration. Randomised controlled trials and prospective
      studies have confirmed the efficacy and safety of this therapy in epilepsy.
      Nevertheless, sporadic cases of ventricular asystole have been reported. To
      evaluate the effect of vagus nerve stimulation therapy on the autonomic nervous
      system, different studies that assess heart function and blood pressure changes
      have been conducted, although the methods employed were not homogeneous. These
      studies have found subtle or no significant changes in heart rate variability and
      blood pressure in epileptic patients. Moreover, this therapy may reduce the risk
      of one of the most lethal conditions in epilepsy-sudden unexpected death.

PMID- 29071464
TI  - Investigating the impact of overnight fasting on intrinsic functional
      connectivity: a double-blind fMRI study.
AB  - The human brain depends mainly on glucose supply from circulating blood as an
      energy substrate for its metabolism. Most of the energy produced by glucose
      catabolism in the brain is used to support intrinsic communication purposes in
      the absence of goal-directed activity. This intrinsic brain function can be
      detected with fMRI as synchronized fluctuations of the BOLD signal forming
      functional networks. Here, we report results from a double-blind, placebo
      controlled, cross-over study addressing changes in intrinsic brain activity in
      the context of very low, yet physiological, blood glucose levels after overnight
      fasting. Comparison of four major resting state networks in a fasting state and a
      state of elevated blood glucose levels after glucagon infusion revealed altered
      patterns of functional connectivity only in a small region of the posterior
      default mode network, while the rest of the networks appeared unaffected.
      Furthermore, low blood glucose was associated with changes in the right
      frontoparietal network after cognitive effort. Our results suggest that fasting
      has only limited impact on intrinsic brain activity, while a detrimental impact
      on a network related to attention is only observable following cognitive effort,
      which is in line with ego depletion and its reliance on glucose.

PMID- 29071465
TI  - Toward whole-brain dopamine movies: a critical review of PET imaging of dopamine
      transmission in the striatum and cortex.
AB  - The mesocorticolimbic dopamine (DA) circuit, comprising the mesolimbic and
      mesocortical DA pathways, plays a crucial role in reward, cognitive control, and
      motivation. The positron emission tomography (PET) radiotracer, [C-11]raclopride,
      has been used widely to image DA receptors and DA changes in the mesolimbic
      pathway before and after pharmacological and behavioral challenges. In certain
      circumstances, properties of traditional kinetic models-used to analyze dynamic
      PET data-are not well-suited to describing the effects of stimulus-induced DA
      release. To combat model shortcomings, the authors have advanced a suite of
      models that characterizes PET data in the presence of time-varying DA release. We
      review select [C-11]raclopride studies of the striatum during cigarette smoking
      to illustrate the advantages of such models. DA receptors occur in lower density
      in the cortex than the striatum. This, as well as higher relative background
      signal, poses a serious challenge to quantitative PET of DA changes in the
      mesocortical system. Novel high affinity radioligands [F-18]fallypride and [C
      11]FLB457 have been used to image mesocortical DA transmission. Models with time
      varying terms may also hold the key to optimizing sensitivity to changes in
      mesocortical DA. As an illustration, we compare recent PET studies of the effect
      of stress on cortical DA release. Finally, we consider some challenges and
      strategies for further optimization of sensitivity of PET to stimulus-induced DA
      changes throughout the whole brain.

PMID- 29071467
TI  - Raltegravir Once-Daily Tablet: A Review in HIV-1 Infection.
AB  - A once-daily tablet formulation (Isentress(r) HD; Isentress(r) 600 mg) of the
      integrase strand transfer inhibitor raltegravir is now available for the
      treatment of HIV-1 infection. The 600 mg tablet has improved bioavailability
      versus the existing twice-daily 400 mg tablet (due, at least in part, to
      differences in tablet dissolution) and the recommended dosage is 1200 mg (i.e.
      two 600 mg tablets) once daily. In combination with emtricitabine/tenofovir
      disoproxil fumarate in treatment-naive adults, once-daily raltegravir 1200 mg
      provided virological suppression non-inferior to that seen with twice-daily
      raltegravir 400 mg over 48 and 96 weeks in the phase 3 ONCEMRK trial. The once
      daily raltegravir regimen was also generally well tolerated in this study,
      displaying a tolerability profile similar to that of the twice-daily regimen. The
      once-daily tablet simplifies and improves the convenience of raltegravir
      regimens, although its impact on adherence has yet to be determined. Thus, once
      daily raltegravir tablets are a convenient alternative to twice-daily raltegravir
      tablets for the treatment of HIV-1, further expanding the therapeutic options
      available to meet the diverse needs of this patient population.

PMID- 29071468
TI  - Toxocariasis: critical analysis of serology in patients attending a public
      referral center for ophthalmology in Brazil.
AB  - PURPOSE: To analyze the contribution of IgG anti-Toxocara antibodies in the
      diagnosis of ocular toxocariasis (OT) in serum samples of patients attending a
      public referral center for ophthalmology in Brazil and to determine the most
      frequent ocular signs and symptoms. STUDY DESIGN: This was a retrospective
      descriptive study of a cohort of outpatients followed from December 1989 to May
      2006. METHODS: IgG anti-Toxocara antibody titers were determined by enzyme-linked
      immunosorbent assay. The results were correlated with the clinical and
      funduscopic findings. RESULTS: Of the diagnoses for the 126 patients, 42 were
      considered as probable OT, 48 as negative, and 36 as inconclusive. The median IgG
      anti-Toxocara antibody titers of the patients with probable OT were significantly
      higher than those of the patients in the negative or inconclusive groups (P =
      0.0001). Higher titers were observed more frequently in patients in the probable
      OT group (P = 0.01) than in the negative group, in which titers were absent or
      lower in most patients (P < 0.0001). The right eye was affected more in the OT
      group than in the negative group (P = 0.01), and inflammation was located mostly
      in the intermediate and posterior poles. The mean age of the patients diagnosed
      with probable OT was significantly lower (mean, 8 years) than that of the
      negative patients (mean, 14.5 years) (P = 0.006). CONCLUSIONS: Higher levels of
      antibodies could help with the diagnosis of OT in patients with symptoms and
      clinical signs; however, negative results cannot exclude possible OT. Conversely,
      patients with negative serology or low titers make the diagnosis of OT less
      likely.

PMID- 29071469
TI  - Ultrastructural analyses of internal limiting membrane excised from highly myopic
      eyes with myopic traction maculopathy.
AB  - PURPOSE: To evaluate the ultrastructure of the internal limiting membranes (ILMs)
      excised during vitrectomy from highly myopic eyes with myopic traction
      maculopathy (MTM). The clinical findings before and after the vitrectomy were
      compared. METHODS: Seven eyes of 7 patients with macular retinoschisis were
      studied. Four of these eyes also had a foveal detachment but without a retinal
      break. All the eyes underwent vitrectomy with the creation of a posterior
      vitreous detachment and ILM peeling. The excised ILMs were examined by
      transmission electron microscopy (TEM). RESULTS: The retinas were reattached in
      all eyes after the vitrectomy. No retinal breaks including macular holes were
      identified intraoperatively. Transmission electron microscopy showed glial cells
      in 4 eyes, retinal pigment epithelium-like cells in 4 eyes, and myofibroblast
      like cells in 4 eyes on the excised ILMs. A newly produced basement membrane
      appeared to merge with the ILM in 5 eyes. Thick collagen was seen in 2 eyes, and
      fibrous long-spacing collagen in the newly synthesized collagen fibers was seen
      in 3 eyes. The cellular components of the glial cells appeared to have migrated
      through the thinner parts of the retina or through a defect of the ILM in 2 eyes.
      CONCLUSIONS: Cells that migrate onto the surface of the ILM synthesize new
      collagen, which can create tangential traction. This may explain the success of
      vitrectomy with ILM peeling in treating MTM in highly myopic eyes.

PMID- 29071471
TI  - The Hidden Genomics of Chlamydia trachomatis.
AB  - The application of whole-genome sequencing has moved us on from sequencing single
      genomes to defining unravelling population structures in different niches, and at
      the -species, -serotype or even -genus level, and in local, national and global
      settings. This has been instrumental in cataloguing and revealing a huge a range
      of diversity in this bacterium, when at first we thought there was little.
      Genomics has challenged assumptions, added insight, as well as confusion and
      glimpses of truths. What is clear is that at a time when we start to realise the
      extent and nature of the diversity contained within a genus or a species like
      this, the huge depth of knowledge communities have developed, through cell
      biology, as well as the new found molecular approaches will be more precious than
      ever to link genotype to phenotype. Here we detail the technological developments
      and insights we have seen during the relatively short time since we began to see
      the hidden genome of Chlamydia trachomatis.

PMID- 29071472
TI  - Immune Interventions to Eliminate the HIV Reservoir.
AB  - Inducing HIV remission is a monumental challenge. A potential strategy is the
      "kick and kill" approach where latently infected cells are first activated to
      express viral proteins and then eliminated through cytopathic effects of HIV or
      immune-mediated killing. However, pre-existing immune responses to HIV cannot
      eradicate HIV infection due to the presence of escape variants, inadequate
      magnitude, and breadth of responses as well as immune exhaustion. The two major
      approaches to boost immune-mediated elimination of infected cells include
      enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to
      eliminate HIV. Specific strategies include increasing the magnitude and breadth
      of T cell responses through therapeutic vaccinations, reversing the effects of T
      cell exhaustion using immune checkpoint inhibition, employing bispecific T cell
      targeting immunomodulatory proteins or dual-affinity re-targeting molecules to
      direct cytotoxic T lymphocytes to virus-expressing cells and broadly neutralizing
      antibody infusions. Methods to steer immune responses to tissue sites where
      latently infected cells are located need to be further explored. Ultimately,
      strategies to induce HIV remission must be tolerable, safe, and scalable in order
      to make a global impact.

PMID- 29071470
TI  - The Challenge of Pharmacotherapy in Children and Adolescents with Epilepsy-ADHD
      Comorbidity.
AB  - Epilepsy is common in children and adolescents where its prevalence is 3.2
      5.5/1000. About one-third of patients also have attention deficit
      hyperactivity/impulsivity disorder (ADHD). The possible relationship between
      epilepsy and ADHD is still unclear, and ADHD symptoms (such as inattention,
      hyperactivity, behavioral disturbances) are frequently considered as adverse
      effects of antiepileptic drugs (AEDs). The literature was searched for data on
      the behavioral effects of AEDs. Phenobarbital is the most frequently reported
      medication to induce symptoms of ADHD, followed by topiramate and valproic acid.
      Phenytoin seems to exert modest effects, while for levetiracetam there are
      contrasting data. Lacosamide induces some beneficial effects on behavior;
      carbamazepine and lamotrigine exert favorable effects on attention and behavior.
      Gabapentin and vigabatrin have limited adverse effects on cognition.
      Oxcarbazepine, rufinamide, and eslicarbazepine do not seem to aggravate or induce
      ADHD symptoms, whereas perampanel can lead to a high incidence of
      hostile/aggressive behavior, which increases with higher dosages. Information
      about the behavioral effects of ethosuximide, zonisamide, tiagabine, pregabalin,
      stiripentol, and retigabine is still limited. Because ADHD significantly affects
      the quality of life of epilepsy patients, the clinical management of this
      neuropsychiatric disorder should be a priority. Methylphenidate is effective most
      children and adolescents with ADHD symptoms and comorbid epilepsy, without a
      significant increase of seizure risk, although data are still limited with few
      controlled trials.

PMID- 29071473
TI  - West Africa 2013 Ebola: From Virus Outbreak to Humanitarian Crisis.
AB  - The 2013 outbreak of Ebola virus disease (EVD) in West Africa constituted a major
      humanitarian crisis. The outbreak numbered over 28,500 cases, more than 10 times
      the number cumulatively registered from all previous EVD outbreaks combined, with
      at least 11,000 deaths, and resulted in billions of dollars of lost economic
      growth to an already impoverished region. The unprecedented scale of West Africa
      2013 took the world by surprise and laid bare deficiencies in our response
      capacity to complex humanitarian disasters of highly infectious and lethal
      pathogens. However, the magnitude of West Africa 2013 also provided a unique
      opportunity and obligation to better understand not only the biology and
      epidemiology of EVD, but also the many scientific, economic, social, political,
      ethical, and logistical challenges in confronting emerging infectious diseases in
      the modern era.

PMID- 29071474
TI  - Molecular Control of HIV and SIV Latency.
AB  - The HIV latent reservoirs are considered as the main hurdle to viral eradication.
      Numerous mechanisms lead to the establishment of HIV latency and act at the
      transcriptional and post-transcriptional levels. A better understanding of
      latency is needed in order to ultimately achieve a cure for HIV. The mechanisms
      underlying latency vary between patients, tissues, anatomical compartments, and
      cell types. From this point of view, simian immunodeficiency virus (SIV)
      infection and the use of nonhuman primate (NHP) models that recapitulate many
      aspects of HIV-associated latency establishment and disease progression are
      essential tools since they allow extensive tissue sampling as well as a control
      of infection parameters (virus type, dose, route, and time).

PMID- 29071475
TI  - Assays to Measure Latency, Reservoirs, and Reactivation.
AB  - HIV-1 persists even in patients who are successfully treated with combination
      antiretroviral therapy. The major barrier to cure is a small pool of latently
      infected resting CD4+ T cells carrying an integrated copy of the viral genome
      that is not expressed while the cells remain in a resting state. Targeting this
      latent reservoir is a major focus of HIV-1 cure research, and the development of
      a rapid and scalable assay for the reservoir is a rate-limiting step in the
      search for a cure. The most commonly used assays are standard PCR assays
      targeting conserved regions of the HIV-1 genome. However, because the vast
      majority of HIV-1 proviruses are defective, such assays may not accurately
      capture changes in the minor subset of proviruses that are replication-competent
      and that pose a barrier to cure. On the other hand, the viral outgrowth assay
      that was used to initially define the latent reservoir may underestimate
      reservoir size because not all replication-competent proviruses are induced by a
      single round of T cell activation in this assay. Therefore, this assay is best
      regarded as a definitive minimal estimate of reservoir size. The best approach
      may be to measure all of the proviruses with the potential to cause viral
      rebound. A variety of novel assays have recently been described. Ultimately, the
      assay that best predicts time to viral rebound will be the most useful to the
      cure effort.

PMID- 29071476
TI  - The Antiviral Immune Response and Its Impact on the HIV-1 Reservoir.
AB  - Latently infected resting memory CD4+ T cells represent a major barrier to HIV-1
      eradication. Studies have shown that it will not be possible to cure HIV-1
      infection unless these cells are eliminated. Latently infected cells probably do
      not express viral antigens and thus may not be susceptible to the HIV-1 specific
      immune response, nevertheless the size and composition of the reservoir is
      influenced by the immune system. In this chapter, we review the different
      components of the HIV-1 specific immune response and discuss how the immune
      system can be harnessed to eradicate the virus.

PMID- 29071477
TI  - Enforced expression of MIR142, a target of chromosome translocation in human B
      cell tumors, results in B-cell depletion.
AB  - MicroRNA142 (MIR142) is a target of chromosome translocations and mutations in
      human B-cell lymphomas. We analyzed an aggressive B-cell lymphoma carrying
      t(8;17)(q24;q22) and t(6;14)(p21;q32), and sought to explore the role(s) of
      MIR142 in lymphomagenesis. t(8;17)(q24;q22) involved MYC on 8q24 and pri-MIR142
      on 17q22. MYC was activated by a promoter substitution by t(8;17)(q24;q22).
      t(8;17)(q24;q22) was an additional event after t(6;14) (p21;q32), which caused
      the over-expression of CCND3. Southern blot analyses revealed that the MIR142
      locus was deleted from the affected allele, whereas Northern analyses showed over
      expression of MIR142 in tumor cells. Although previous studies reported an over
      expression of mutations in MIR142 in B-cell lymphomas, limited information is
      available on the functions of MIR142 in lymphomagenesis. Therefore, we generated
      bone marrow transplantation (BMT) and transgenic (EMU/mir142) mice, which showed
      enforced expression in hematopoietic progenitor cells and B cells, respectively.
      BMT mice showed decreased numbers of all lineage-positive cells, particularly B
      cells, in peripheral blood. EMU/mir142 mice showed decreased numbers of IgM
      positive splenocytes, and exhibited altered B-cell phenotypic changes induced by
      lipopolysaccharide. Our results suggest that over-expression of MIR142 alters B
      cell differentiation, implying multi-step lymphomagenesis together with MYC
      activation and CCND3 over-expression.

PMID- 29071478
TI  - Gene analysis of inherited antithrombin deficiency and functional analysis of
      abnormal antithrombin protein (N87D).
AB  - Inherited antithrombin (AT) deficiency is one of the most clinically significant
      forms of congenital thrombophilia and follows an autosomal dominant mode of
      inheritance. We analyzed SERPINC1 in a patient who developed deep-vein thrombosis
      and low AT activity during pregnancy, and identified a novel missense mutation
      c.259A>G (p.Asn87Asp; N87D). Surprisingly, analysis of the parents' DNA showed
      that they did not possess this mutant, and thus, it may have been due to a de
      novo mutation. We also expressed this mutant AT protein in COS-1 cells and
      compared its intracellular localization and intracellular and extracellular
      antigen levels with that of wild-type AT. The expression experiment did not
      reveal a significant difference in the antigen levels of the mutant and wild-type
      AT in the cell lysate, but the mutant AT antigen level was markedly lower than
      that of its wild-type counterpart in the COS-1 cell supernatant.
      Immunofluorescence did not indicate any difference between the mutant and wild
      type AT in terms of cytoplasmic localization of fluorescence signals. Our
      findings suggest that the patient's AT deficiency may have been caused by
      impaired extracellular secretion of mutant AT protein p.Asn87Asp.

PMID- 29071479
TI  - Association of potentially inappropriate medications with outcomes of inpatient
      geriatric rehabilitation : A prospective cohort study.
AB  - BACKGROUND: Higher age is associated with multimorbidity, which may lead to
      polypharmacy and potentially inappropriate medication (PIM). OBJECTIVE: To
      evaluate whether PIM on admission for geriatric inpatient rehabilitation is
      associated with rehabilitation outcome regarding mobility and quality of life.
      MATERIAL AND METHODS: A total of 210 patients were included. Medications at
      hospital admission were analyzed with the Screening Tool of Older Persons'
      potentially inappropriate Prescriptions (STOPP) and the number of PIMs individual
      patients were taking was determined. The study population was then divided into
      two groups, one with and one without PIM. The main rehabilitation outcomes,
      quality of life and mobility, were assessed on admission and discharge.
      Associations between PIM and the main outcomes were analyzed using the two-tailed
      Student's t-test and Spearman correlations. RESULTS: In total 131 PIMs were
      identified by STOPP. Of the patients 91 (43%) were taking at least 1 PIM, and 119
      patients (57%) were not taking any PIM. Patients with no PIM had a significantly
      better quality of life on admission (p < 0.05) and discharge (p < 0.005). The
      number of PIMs was not associated with the rehabilitation outcomes mobility and
      quality of life (Spearman's rho = -0.01, p = 0.89 and rho = -0.02, p = 0.7,
      respectively). The quality of life and mobility increased identically in both
      groups from admission to discharge but the group with PIM did not reach the
      levels of those without PIM. CONCLUSION: The use of PIM may have a negative
      impact on the quality of life of elderly people but patients with and without PIM
      achieved comparable improvements in quality of life and mobility. Further studies
      are required to assess the long-term outcomes of patients taking PIM following
      inpatient rehabilitation.

PMID- 29071480
TI  - Obesity, Appetite, and the Prefrontal Cortex.
AB  - PURPOSE OF REVIEW: Obesity is a chronic illness and its prevalence is growing
      worldwide and numerous factors play a role in the regulation of food intake. The
      prefrontal cortex (PFC) is involved in high-order executive function, regulation
      of limbic reward regions, and the inhibition of impulsive behaviors.
      Understanding the role of the PFC in the control of appetite regulation may
      contribute to a greater understanding of the etiology of obesity and could
      improve weight loss outcomes. RECENT FINDINGS: Neuroimaging studies have
      identified lower activation in the left dorsolateral PFC (DLPFC) in obese
      compared to lean individuals and others have focused on efforts to improve
      cognitive control in this area of the brain. The DLPFC is a critical brain area
      associated with appetitive control, food craving, and executive functioning,
      indicating a candidate target area for treatment. Further studies are needed to
      advance our understanding of the relationship between obesity, appetite, and the
      DLPFC and provide validation for the effectiveness of novel treatments in
      clinical populations.

PMID- 29071483
TI  - [S1 guidelines on diagnostics and treatment of ANCA-associated vasculitis].

PMID- 29071482
TI  - [Nontuberculous mycobacterial infections].
AB  - Nontuberculous mycobacterial (NTM) are found ubiquitously in the environment and
      are usually of low pathogenicity. Infection occurs via inhalation of aerosols,
      and some species may cause severe infections. The incidence of NTM infections is
      rising worldwide. The risk of developing NTM disease depends on the
      susceptibility of the host as well as the frequency and duration of exposure. In
      addition to congenital immune deficiencies and immunosuppressive therapy,
      structural lung and systemic diseases, including rheumatoid arthritis (RA), are
      associated with an increased risk for NTM infections. The immune response to NTM
      is complex and relies on the interplay between professional phagocytes and
      lymphoid cells. This interplay is concerted by three key cytokines: interleukin
      12 (IL-12), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN
      gamma). Targeted immunotherapies, e. g., treatment with TNF inhibitors, interfere
      with these essential pathways and increase the risk of NTM infection
      significantly. This review focuses on the relationship between the immune
      response to NTM and intrinsic and iatrogenic dispositions for NTM infection, with
      an emphasis on RA.

PMID- 29071484
TI  - Robotic right colectomy with intracorporeal anastomosis for malignancy.
AB  - Techniques for robotic resection of the right colon have not been extensively
      published or adopted. We report our initial experience of robotic right colectomy
      with intracorporeal anastomosis and specimen extraction through a Pfannenstiel
      incision retrospectively. Twenty-one consecutive patients with a right colon
      cancer (n = 18) or polyp too large to remove endoscopically (n = 3) were treated
      at Mayo Clinic Rochester, Minnesota. Main outcomes measured were estimated blood
      loss, operative time, conversion rate, return of gastrointestinal function,
      length of stay, overall and severe complications, discharge status, and
      pathology. All 21 procedures were technically successful without the need for
      conversion. The mean total operative time was 250 +/- 56 min, estimated blood
      loss was less than 100 mL in 19 (90%), only 1 (5%) ileus occurred, mean length of
      stay and return of gastrointestinal function was 4 +/- 1.3 and 1 +/- 0.6 days,
      respectively, only 1 (5%) patient experienced a Dindo grade >= 3 complication,
      and 20 (95%) were discharged to home. Mean number of nodes resected was 26 +/-
      12. Tumors were diagnosed as stage 0 in 3 (14%), stage I in 7 (33%), stage II in
      4 (19%), stage III in 6 (28%), and stage IV in 1 (5%). Main limitations were
      nonrandomized nature, single institution experience, small patient sample size,
      and procedures only being performed by two surgeons. Finally, we conclude that
      robotic right colectomy with central mesocolic excision, intracorporeal
      anastomosis, and extraction through a Pfannenstiel incision is technically
      feasible, efficacious, oncologically acceptable, and safe to perform.

PMID- 29071481
TI  - Ultra-processed Food Intake and Obesity: What Really Matters for Health
      Processing or Nutrient Content?
AB  - PURPOSE OF REVIEW: The aim of this narrative review was to summarize and critique
      recent evidence evaluating the association between ultra-processed food intake
      and obesity. RECENT FINDINGS: Four of five studies found that higher purchases or
      consumption of ultra-processed food was associated with overweight/obesity.
      Additional studies reported relationships between ultra-processed food intake and
      higher fasting glucose, metabolic syndrome, increases in total and LDL
      cholesterol, and risk of hypertension. It remains unclear whether associations
      can be attributed to processing itself or the nutrient content of ultra-processed
      foods. Only three of nine studies used a prospective design, and the potential
      for residual confounding was high. Recent research provides fairly consistent
      support for the association of ultra-processed food intake with obesity and
      related cardiometabolic outcomes. There is a clear need for further studies,
      particularly those using longitudinal designs and with sufficient control for
      confounding, to potentially confirm these findings in different populations and
      to determine whether ultra-processed food consumption is associated with obesity
      independent of nutrient content.

PMID- 29071485
TI  - On the learning difficulty of visual and auditory modal concepts: Evidence for a
      single processing system.
AB  - The logic operators (e.g., "and," "or," "if, then") play a fundamental role in
      concept formation, syntactic construction, semantic expression, and deductive
      reasoning. In spite of this very general and basic role, there are relatively few
      studies in the literature that focus on their conceptual nature. In the current
      investigation, we examine, for the first time, the learning difficulty
      experienced by observers in classifying members belonging to these primitive
      "modal concepts" instantiated with sets of acoustic and visual stimuli. We report
      results from two categorization experiments that suggest the acquisition of
      acoustic and visual modal concepts is achieved by the same general cognitive
      mechanism. Additionally, we attempt to account for these results with two models
      of concept learning difficulty: the generalized invariance structure theory model
      (Vigo in Cognition 129(1):138-162, 2013, Mathematical principles of human
      conceptual behavior, Routledge, New York, 2014) and the generalized context model
      (Nosofsky in J Exp Psychol Learn Mem Cogn 10(1):104-114, 1984, J Exp Psychol
      115(1):39-57, 1986).

PMID- 29071486
TI  - Fragments of e-Cadherin as Biomarkers of Non-erosive Reflux Disease.
AB  - BACKGROUND: Approximately, 20% of patients with heartburn and normal endoscopic
      findings do not symptomatically improve on proton pump inhibitor (PPI) therapy
      making diagnosis and treatment uncertain. A biomarker distinguishing PPI
      responsive from PPI-refractory heartburn is desirable. AIMS: We performed a pilot
      study assessing whether carboxy(C)-terminal fragments (CTFs) of e-cadherin in
      esophageal biopsies or amino(N)-terminal fragments (NTFs) of e-cadherin in serum
      could serve this purpose. METHODS: Twenty-nine patients with endoscopy-negative
      heartburn had esophageal biopsies for CTFs on Western blot and blood for serum
      NTFs on ELISA. All patients received dexlansoprazole 30 mg daily for 4 weeks, and
      heartburn was assessed by daily diary entry. Post-treatment blood samples were
      obtained for serum NTFs. A control group without GERD symptoms (n = 6) had
      biopsies for CTFs and a second control group (n = 20) blood serum for serum NTFs.
      RESULTS: Twenty-seven of 29 patients (93.1%) with endoscopy-negative heartburn,
      but 0 of 6 controls, were positive for CTFs. All patients and controls had
      measureable serum NTFs, but mean NTFs were significantly higher in those with PPI
      responsive heartburn compared to those with PPI-refractory heartburn and
      controls. Following treatment, 24 of 29 (82.8) patients had relief of heartburn,
      which associated with a decline in mean NTFs compared to controls. NTFs in PPI
      refractory patients (n = 5) were similar to controls before and after PPI
      therapy. CONCLUSIONS: When heartburn responds to PPI, elevated serum NTFs decline
      to normal. These data suggest that cleaved products of e-cadherin may serve as
      biomarkers of NERD. Further data are needed to assess and confirm this concept.

PMID- 29071487
TI  - "Blueberry Muffin" Rash and Neonatal Cholestatic Liver Failure.

PMID- 29071490
TI  - High-Throughput Proteomic Analysis of Fresh-Frozen Biopsy Tissue Samples Using
      Pressure Cycling Technology Coupled with SWATH Mass Spectrometry.
AB  - In the era of precision medicine, there is an increasing need to measure several
      thousand proteins expressed in minimal amount of fresh-frozen biopsy tissue
      samples from clinical cohorts. Here we present the detailed protocol for high
      throughput proteomic analysis of less than 1 mg fresh-frozen tissue sample using
      pressure cycling technology (PCT), SWATH mass spectrometry, and OpenSWATH
      workflow. The PCT procedures enable simultaneous analysis of 16 biopsy tissue
      samples per batch, followed by SWATH analysis of about 15 samples per mass
      spectrometer per working day. The thus generated SWATH maps can be perpetually
      analyzed in silico, offering a practical solution for digital biobanking.

PMID- 29071488
TI  - Effect of Perceived Discrimination on Depressive Symptoms in 1st- and 2nd
      Generation Afghan-Americans.
AB  - While it is well established that Afghan refugees are disproportionately affected
      by mental health problems, limited evidence exists concerning the psychosocial
      needs of their children who are transitioning to adulthood in the United States;
      that is, of 1st- and 2nd-generation Afghan-Americans. The purpose of this study
      was to examine the effect of perceived discrimination on depressive symptoms in
      this population, and to determine whether discrimination is buffered by ethnic
      identity and social support. A convenience sample of 133 1st- and 2nd-generation
      Afghan-Americans participated in this study by completing a brief survey. We used
      OLS regression methods to control for covariates, and to sequentially test study
      hypotheses. The results show that perceived discrimination was significantly
      associated with high levels of depression. Furthermore, the effect of
      discrimination on depression was not buffered by ethnic identity or social
      support. We found that perceived discrimination was a significant source of
      stress and a risk-factor for negative mental health outcomes among 1st- and 2nd
      generation Afghan-Americans. Future research should examine additional pre
      dispositional and protective factors for discriminatory experiences and
      associated health outcomes.

PMID- 29071491
TI  - Correction to: IRIS study: a phase II study of the steroid sulfatase inhibitor
      Irosustat when added to an aromatase inhibitor in ER-positive breast cancer
      patients.
AB  - In the original publication of the article, a part of acknowledgement section was
      missed out. The omitted acknowledgement is given below: 'The study was
      coordinated by the Imperial Clinical Trials Unit-Cancer, Imperial College London
      and Sponsored by Imperial College London. The Imperial Clinical Trials Unit
      receives funding from the National Institute for Health (NIHR) Biomedical
      Research Centre based at Imperial College Healthcare NHS Trust and Imperial
      College London. The views expressed are those of the author(s) and not
      necessarily those of the NHS, the NIHR or the Department of Health. This study
      was supported by Imperial Experimental Cancer Medicine Centre and Cancer Research
      UK Imperial Centre'.

PMID- 29071489
TI  - Ambulatory Blood Pressure Monitoring in Children and Adolescents: a Review of
      Recent Literature and New Guidelines.
AB  - PURPOSE OF REVIEW: This is a review of ambulatory blood pressure monitoring
      (ABPM) use in pediatrics, focusing on research published in the last 3 to 4
      years. RECENT FINDINGS: Recent data has shown that ABPM is more strongly
      associated with end-organ damage than casual BP, and that obesity and secondary
      causes of hypertension are strongly associated with nocturnal hypertension. There
      is evidence that ABPM is useful in management of a larger variety of diagnoses
      than previously thought. New guidelines from the American Academy of Pediatrics
      recognize the importance of ABPM in the management of pediatric hypertension.
      ABPM has an important and growing role in the diagnosis and management of
      hypertension in children and adolescents. Future efforts should include
      developing more generalizable normative data and investigating associations
      between pediatric ABPM results and adult outcomes.

PMID- 29071493
TI  - Effect of host framework on the diffusion process in microporous material: a
      molecular dynamics simulation investigation.
AB  - One of the central assumptions when a particle moves through a window in
      microporous materials is that interaction of the diffusing particle with the
      silicon (Si) and aluminum (Al) atoms of the framework can be neglected, as the
      presence of bulkier oxygen in the host structure is thought to hinder close
      proximity of the diffusing particle to Si and Al. We examine this assumption,
      exploring the diffusion path and cross-checking the bottleneck associated with
      the diffusion process. Our study reveals that short-range interactions between
      the diffusing species and Si/Al of the host have a significant effect on the
      diffusion process. Guest-host interaction energy increases significantly if
      interaction between Si and Al atoms with the diffusing species is considered. The
      self-diffusion coefficient (D) decreases significantly in the linear regime,
      whereas in the anomalous regime, surprisingly, D increases. The increase in D is
      due to a decrease in the activation energy in the anomalous regime, whereas in
      the linear regime, activation energy increases, thus D decreases. Graphical
      abstract a Interaction energies (E a) for different LJ potential for guest-guest
      interactions (sigmagg) along the diffusion path; b correspondingdiffusivity
      values.

PMID- 29071492
TI  - Sensation of the autologous reconstructed breast improves quality of life: a
      pilot study.
AB  - PURPOSE: The number of breast cancer survivors continues to grow. Due to
      refinements in operating techniques, autologous breast reconstruction has become
      part of standard care. Impaired sensation remains a debilitating side effect with
      a significant impact on the quality of life. Microsurgical nerve coaptation of a
      sensory nerve has the potential to improve sensation of the reconstructed breast.
      This study investigates the effect of improved sensation of the reconstructed
      breast on the quality of life in breast cancer survivors. METHODS: A
      retrospective cohort study was performed in the Maastricht University Medical
      Center. Patients undergoing a DIEP flap breast reconstruction between January
      2015 and January 2016 were included. The primary outcome was quality of life
      (BREAST-Q domain 'physical well-being of the chest'). The Semmes-Weinstein
      monofilaments were used for objective sensation measurement of the reconstructed
      breast(s). RESULTS: Eighteen patients with and 14 patients without nerve
      coaptation responded. Nipple reconstruction was the only characteristic that
      differed statistically significant between both groups (p = 0.04). The BREAST-Q
      score for the domain physical well-being of the chest was 77.89 +/- 18.89 on
      average in patients with nerve coaptation and 66.21 +/- 18.26 in patients without
      nerve coaptation (p = 0.09). Linear regression showed a statistically significant
      relation between objectively measured sensation and BREAST-Q score for the domain
      physical well-being of the chest with a regression coefficient of - 13.17 +/-
      3.61 (p < 0.01). CONCLUSIONS: Improved sensation in the autologous reconstructed
      breast, with the addition of microsurgical nerve coaptation, has a statistical
      significant positive impact on the quality of life in breast cancer survivors
      according to the BREAST-Q.

PMID- 29071494
TI  - Highly efficient isolation and release of circulating tumor cells based on size
      dependent filtration and degradable ZnO nanorods substrate in a wedge-shaped
      microfluidic chip.
AB  - Circulating tumor cells (CTCs) have been regarded as the major cause of
      metastasis, holding significant insights for tumor diagnosis and treatment.
      Although many efforts have been made to develop methods for CTC isolation and
      release in microfluidic system, it remains significant challenges to realize
      highly efficient isolation and gentle release of CTCs for further cellular and
      bio-molecular analyses. In this study, we demonstrate a novel method for CTC
      isolation and release using a simple wedge-shaped microfluidic chip embedding
      degradable znic oxide nanorods (ZnNRs) substrate. By integrating size-dependent
      filtration with degradable nanostructured substrate, the capture efficiencies
      over 87.5% were achieved for SKBR3, PC3, HepG2 and A549 cancer cells spiked in
      healthy blood sample with the flow rate of 100 MUL min-1. By dissolving ZnNRs
      substrate with an extremely low concentration of phosphoric acid (12.5 mM), up to
      85.6% of the captured SKBR3 cells were released after reverse injection with flow
      rate of 100 MUL min-1 for 15 min, which exhibited around 73.6% cell viability
      within 1 h after release to around 93.9% after re-cultured for 3 days. It is
      conceivable that our microfluidic device has great potentials in carrying on cell
      based biomedical studies and guiding individualized treatment in the future.

PMID- 29071495
TI  - Open treatment of ankle fracture as inpatient increases risk of complication.
AB  - BACKGROUND: Ankle fracture is one of the most common injuries treated by
      orthopaedic surgeons, and its incidence is only expected to rise with an aging
      population. It is also associated with often costly complications, yet there is
      little literature on risk factors, especially modifiable ones, driving these
      complications. The aim of this study is to reveal whether inpatient treatment
      after ankle fracture is associated with higher incidence of postoperative
      complications. As the USA moves towards a bundled payment healthcare system, it
      is imperative that orthopaedists maximize patient outcome and quality of care
      while also reducing overall costs. MATERIALS AND METHODS: We used the American
      College of Surgeons National Surgical Quality Improvement Program database to
      compare complication rates between inpatient and outpatient treatment of ankle
      fracture. We collected patient demographics, comorbidities, and postoperative
      complications from both groups, then compared treatments using a multinomial
      logistic regression model. RESULTS: We identified 7383 patients, with 2630 (36%)
      in the outpatient and 2630 (36%) in the inpatient group. Of these, 104 (4.0%)
      inpatients compared with 52 (2.0%) outpatients developed a complication (p <
      0.001). CONCLUSIONS: Inpatients developed major complications including deep
      wound infection and pulmonary embolism, as well as minor complications such as
      pneumonia and urinary tract infection, at significantly greater rates. As
      reimbursement models begin to incorporate value-based care, orthopaedic surgeons
      need to be aware of factors associated with increased incidence of postoperative
      complications. LEVEL OF EVIDENCE: Level III retrospective comparative study.

PMID- 29071496
TI  - A matched comparison of laparoscopic versus open inguinal hernia repair in
      patients with liver disease using propensity score matching.
AB  - PURPOSE: Patients with liver cirrhosis may require inguinal hernia repair. It is
      unknown if surgical approach, laparoscopic or open, affects outcomes in this high
      risk patient population. This study compares complications, deaths, and length of
      stay between open and laparoscopic inguinal hernias in patients with liver
      disease. METHODS: All patients (N = 145,780) who were diagnosed with inguinal
      hernia (ICD-9-codes: 550.00, 550.02, 550.10, 550.12, 550.90, and 550.92) and had
      unilateral repair surgery (current procedure codes: 49505, 49507, 49525, and
      49650) between 2005 and 2014 were identified from the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Data
      collected included patient demographics, comorbid conditions, postsurgical
      diagnosis, and outcomes. Multivariate logistic regression models were employed to
      evaluate the associations between various outcomes and surgical approach.
      RESULTS: The percentage of open inguinal hernia repair (OIHR) decreased from
      84.08% in 2005 to 74.66% in 2014. The mean MELD score was 9.09 +/- 4.02 among
      open surgery patient group, which was higher than the mean MELD score (8.03 +/-
      2.78) among laparoscopic surgery group. After propensity score matching for
      patient characteristics, open and laparoscopic inguinal hernia groups had similar
      length of stay with a slightly longer operation time being observed among
      laparoscopic group. Overall complications rates were similar (OR 0.87, 95% CI 0.
      1.15, p = 0.32) as was overall mortality (0.27% among open surgery patients and
      0.12% among laparoscopic patients, OR 0.42, 95% CI 0.15-1.21, p = 0.96).
      CONCLUSION: Laparoscopic inguinal hernia repair demonstrates similar morbidity
      and mortality when compared to open repairs in patients with liver disease
      suggesting that both are viable repair options.

PMID- 29071497
TI  - The use of adjuncts to reduce seroma in open incisional hernia repair: a
      systematic review.
AB  - BACKGROUND: Seroma formation remains a common complication after an incisional
      hernia repair. The use of surgical drains is widespread, but evidence for their
      use and other adjuncts is limited. Our aim was to perform a systematic review of
      the literature on techniques used to reduce the incidence of post-operative
      seroma formation. METHODS: A systematic search of PubMed and Embase databases was
      conducted using terms including "incisional hernia" and "seroma". All studies on
      adults undergoing open incisional hernia repair with at least one intervention
      designed to reduce seroma formation were included. RESULTS: Of the 1093 studies
      identified, 9 met the inclusion criteria. Medical talc: one cohort study of 74
      patients undergoing talc application following pre-peritoneal mesh placement
      found a significantly decreased rate of seroma formation of 20.8 versus 2.7% (p <
      0.001), but a retrospective study including 21 patients with onlay mesh found an
      increased rate of 76% seroma formation from 9.5% (p = 0.001). Fibrin glue: one
      comparative study including 60 patients found a reduction in seroma formation
      from 53 to 10% (p = 0.003), whereas a retrospective study of 250 patients found
      no difference (11 vs. 4.9% p = 0.07). Negative pressure wound therapy: four
      retrospective studies including a total of 358 patients found no difference in
      seroma outcome. Others: one randomised study of 42 patients undergoing either
      suction drainage or "quilting" sutures found no difference in seroma formation.
      CONCLUSIONS: There is currently insufficient quality evidence to recommend any of
      the investigated methods, some of which incur significant additional cost.

PMID- 29071498
TI  - Trocar site hernia following laparoscopic cholecystectomy: a 10-year single
      center experience.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) is the gold standard of treatment
      for patients with symptomatic cholelithiasis. Compared to open cholecystectomy,
      LC is associated with significantly lower postoperative complications. Trocar
      site hernia (TSH) is an uncommon, but potentially dangerous, complication of LC.
      The aim of this study was to evaluate the incidence of TSH following LC. METHODS:
      The records of all patients who underwent elective LC between January 2004 and
      December 2013 were retrospectively reviewed. The open technique with a vertical
      incision infraumbilically was used to establish pneumoperitoneum. Two or three
      other skin incisions were made and trocars were inserted. In all cases, only the
      fascia at the site of infra-umbilical incision was closed. Following hospital
      discharge, all patients were regularly re-examined 1, 4 and 52 weeks
      postoperatively and were contacted by phone during November-December 2015. Based
      on the findings from clinical and telephone follow-ups, the incidence of TSH was
      recorded. Using univariate/multivariate analysis, we investigated several
      variables to identify risk factors for TSH development. RESULTS: During the study
      period, 1172 patients were eligible and included in the final analysis. Seven
      patients (0.6%) presented TSH at 1-year follow-up. At the end of the study and
      with a mean follow-up of 65.86 +/- 25.19 months, 11 patients (0.94%) presented
      TSH. Interestingly, all TSHs were developed at the infra-umbilical site.
      Multivariate analysis identified obesity as an independent risk factor for TSH.
      CONCLUSION: The incidence of TSH following LC is considerably low. Obesity is an
      independent risk factor for TSH development, while closure of fascial incision of
      10 mm below the xiphoid is not justified.

PMID- 29071499
TI  - Lactase persistence, milk intake, and mortality in the Danish general population:
      a Mendelian randomization study.
AB  - Meta-analyses have suggested no association between milk intake and mortality.
      Since only few studies have been conducted, we investigated the association
      between the lactase persistent genetic variant LCT-13910 C/T (rs4988235), a proxy
      for long-term low and high intake of milk, and mortality. We used two Danish
      population-based studies with self-reported intake of milk and genotyping for LCT
      13910 C/T. We obtained information on all-cause and cause-specific mortality
      (cardiovascular and cancer) from the national Danish registries. We used
      multivariable adjusted Cox regression to assess the association between milk
      intake and mortality in 74,241 individuals, and both logistic and Cox-regression
      to assess the association between genetic lactase persistence and mortality in
      82,964 individuals using a Mendelian randomization design. We applied per T
      allele, co-dominant and dominant models. During a mean follow-up of 7 years, 9759
      individuals died, 2166 from cardiovascular disease, and 2822 from cancer.
      Observationally, there was no association between intake of skimmed milk and all
      cause or cardiovascular mortality, and we did not find any associations between
      intake of semi-skimmed or whole milk with all-cause or cause-specific mortality.
      Intake of skimmed milk was associated with lower cancer mortality with a hazard
      ratio of 0.97 (95% CI 0.96-1.00) per doubling in milk intake. Per T-allele, milk
      intake increased with 0.58 (0.50-0.68) glasses/week. Genetically, we found no
      associations between the lactase persistent LCT-13910 C/T genotype and all-cause
      or cause-specific mortality; per T-allele OR (95% CI) for all-cause mortality was
      1.02 (0.97-1.06). Our study did not provide strong evidence of observational or
      genetic associations between milk intake and all-cause or cause-specific
      mortality.

PMID- 29071501
TI  - All Clear.

PMID- 29071500
TI  - Temporal association patterns and dynamics of amyloid-beta and tau in Alzheimer's
      disease.
AB  - The elusive relationship between underlying pathology and clinical disease
      hampers diagnosis of Alzheimer's disease (AD) and preventative intervention
      development. We seek to understand the relationship between two classical AD
      biomarkers, amyloid-beta1-42 (Abeta1-42) and total-tau (t-tau), and define their
      trajectories across disease development, as defined by disease onset at diagnosis
      of mild cognitive impairment (MCI). Using longitudinal data from the Alzheimer's
      Disease Neuroimaging Initiative (ADNI), we performed a correlation analysis of
      biomarkers CSF Abeta1-42 and t-tau, and longitudinal quantile analysis. Using a
      mixed effects model, with MCI onset as an anchor, we develop linear trajectories
      to describe the rate of change across disease development. These trajectories
      were extended through the incorporation of data from cognitively normal, healthy
      adults (aged 20-62 years) from the literature, to fit sigmoid curves by means of
      non-linear least squares estimators, to create curves encompassing the 50 years
      prior to MCI onset. A strong right-angled relationship between the biomarkers
      Abeta1-42 and t-tau is detected, implying a highly non-linear relationship. The
      rate of change of Abeta1-42 is correlated with the baseline concentration per
      quantile, reflecting a reduction in the rate of loss across disease within
      subjects. Regression models reveal significant amyloid loss relative to MCI onset
      (- 2.35 pg/mL/year), compared to minimal loss relative to AD onset (- 0.97
      pg/mL/year). Tau accumulates consistently relative to MCI and AD onset, (2.05
      pg/mL/year) and (2.46 pg/mL/year), respectively. The fitted amyloid curve shows
      peak loss of amyloid 8.06 years prior to MCI diagnosis, while t-tau exhibits peak
      accumulation 14.17 years following MCI diagnosis, with the upper limit not yet
      reached 30 years post diagnosis. Biomarker trajectories aid unbiased, objective
      assessment of disease progression. Quantitative trajectories are likely to be of
      use in clinical trial design, as they allow for a more detailed insight into the
      effectiveness of treatments designed to delay development of biological disease.

PMID- 29071503
TI  - Corrections to: Use of the BOADICEA Web Application in clinical practice:
      appraisals by clinicians from various countries.
AB  - The article "Use of the BOADICEA Web Application in clinical practice: appraisals
      by clinicians from various countries" written by Anne Bredart . Jean-Luc Kop .
      Antonis C. Antoniou . Alex P. Cunningham . Antoine De Pauw .Marc Tischkowitz .
      Hans Ehrencrona . Sylvie Dolbeault . Leonore Robieux . Kerstin Rhiem .Douglas F.
      Easton . Peter Devilee . Dominique Stoppa-Lyonnet. Rita Schmutlzer, was
      originally published electronically on the publisher's internet portal (currently
      SpringerLink) on 16th June 2017 without open access.

PMID- 29071502
TI  - Phenotypic and genotypic heterogeneity of Lynch syndrome: a complex diagnostic
      challenge.
AB  - Lynch syndrome is the hereditary disorder that most frequently predisposes to
      colorectal cancer as well as predisposing to a number of extracolonic cancers,
      most prominently endometrial cancer. It is caused by germline mutations in the
      mismatch repair genes. Both its phenotype and genotype show marked heterogeneity.
      This review gives a historical overview of the syndrome, its heterogeneity, its
      genomic landscape, and its implications for complex diagnosis, genetic counseling
      and putative implications for immunotherapy.

PMID- 29071504
TI  - Long-term prognosis and factors associated with damage accrual in Japanese
      patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Using a single-center cohort of Japanese patients with SLE, we
      attempted to clarify the long-term outcome and factors associated with damage
      accrual using the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology Damage Index (SDI). METHODS: We examined a cohort of 557
      patients who had been referred to Niigata University Hospital and diagnosed as
      having SLE between 1961 and 2013. The patients' data at the latest visit were
      collected from their clinical records, and causes of death were defined on the
      basis of those data. Survival from the time of diagnosis was calculated by the
      Kaplan-Meier method. The SDI was calculated and analyzed using Spearman's
      correlation coefficient and stepwise multiple regression analysis to reveal the
      factors associated with any organ damage. RESULTS: Data from 458 of the patients
      were successfully obtained. The overall 5-year survival rate was 92.2%, and
      patients diagnosed after 2000 had a significantly high 5-year survival rate of
      96.4%. Stepwise multiple regression analysis selected serum creatinine levels (B
      = 0.6051, p < 0.0001), age (standardized beta = 0.2762, p < 0.001), hypertension
      (standardized beta = 0.2267, p < 0.001), and antiphospholipid antibody syndrome
      (standardized beta = 0.1533, p = 0.005) as positive independent variables,
      whereas administration of bisphosphonate (standardized beta = - 0.1295, p =
      0.016) was selected as a negative independent variable. CONCLUSION: These results
      suggest that Japanese patients with SLE have a favorable long-term prognosis, and
      also indicate that disease control as well as management of chronic complications
      such as hypertension and osteoporosis has possible effects for prevention of
      organ damage.

PMID- 29071505
TI  - An equation to estimate the renal cortex volume in chronic kidney disease
      patients.
AB  - BACKGROUND: The renal cortex volume is associated with the kidney function and
      chronic kidney disease (CKD) risk factors, and it may also be a prognostic
      factor. We aimed to create an equation to estimate the renal cortex volume of CKD
      patients in day-to-day clinical practice. METHODS: The subjects included 116
      ethnic Japanese CKD patients who were >= 18 years of age. The renal size (length,
      width and thickness) was measured by ultrasound. The body height, weight, year of
      age, sex, birth weight, gestational age, diabetes status, hypertension status,
      family history of CKD and dialysis and estimated glomerular filtration rate
      (eGFR) were collected as expected dependent variables. We made models for the
      equation regarding the renal cortex volume measured by non-contrast magnetic
      resonance imaging as a true renal cortex volume. Stepwise multiple linear
      regression analyses were performed with the log-transformation of dependent and
      independent variables. The accuracy of the models was compared using the leave
      one out cross-validation method. RESULTS: The estimated volume of the renal
      cortex (cm3) = 0.012 * renal length (cm)0.92 * width (cm)0.53 * body weight
      (kg)0.40 * body height (cm)0.67 * eGFR (ml/min/1.73 m2)0.22 * 1.12 if diabetes.
      The adjusted R 2 value and the accuracy within 30 and 50% were 0.73, 0.94 and
      0.99, respectively. CONCLUSIONS: This study provided a new method for estimating
      the renal cortex volume in day-to-day clinical practice.

PMID- 29071507
TI  - Posttranslational Modification of Sodium Channels.
AB  - Voltage-gated sodium channels (VGSCs) are critical determinants of excitability.
      The properties of VGSCs are thought to be tightly controlled. However, VGSCs are
      also subjected to extensive modifications. Multiple posttranslational
      modifications that covalently modify VGSCs in neurons and muscle have been
      identified. These include, but are not limited to, phosphorylation,
      ubiquitination, palmitoylation, nitrosylation, glycosylation, and SUMOylation.
      Posttranslational modifications of VGSCs can have profound impact on cellular
      excitability, contributing to normal and abnormal physiology. Despite four
      decades of research, the complexity of VGSC modulation is still being determined.
      While some modifications have similar effects on the various VGSC isoforms,
      others have isoform-specific interactions. In addition, while much has been
      learned about how individual modifications can impact VGSC function, there is
      still more to be learned about how different modifications can interact. Here we
      review what is known about VGSC posttranslational modifications with a focus on
      the breadth and complexity of the regulatory mechanisms that impact VGSC
      properties.

PMID- 29071506
TI  - Opacity of big toenail predicts poor prognosis in patients with end-stage renal
      disease on hemodialysis.
AB  - BACKGROUND: The impact of nail abnormalities on prognosis in hemodialysis
      patients is unknown. This study investigated whether toenail opacity as a readout
      of nail abnormalities predicted prognosis in hemodialysis patients. METHODS: In
      this observational study, 494 eligible hemodialysis patients who received
      hemodialysis at Oyokyo Kidney Research Institute between September 2010 and
      December 2015 were included. The presence of nail abnormalities was objectively
      evaluated by big toenail opacity ratio measurement. Primary endpoint was overall
      survival, and secondary endpoints were lower limb amputation and determination of
      risk factors for poor prognosis among patient demographics, comorbidities, blood
      tests, and big toenail opacity. Overall survival and lower limb survival were
      evaluated using the Kaplan-Meier method with log-rank test. Multivariate Cox
      regression analyses assessed predictors for poor prognosis. RESULTS: Big toenail
      opacity was found in 259 (52%) patients. Patients with big toenail opacity were
      significantly older, had shorter duration of dialysis, higher prevalence rates of
      diabetes mellitus (DM), cardiovascular disease (CVD), and higher mortality rates
      than those without opacity. Presence of big toenail opacity predicted poor
      prognosis for both overall and lower limb survival. Multivariate Cox regression
      analyses revealed serum albumin, the presence of DM and big toenail opacity were
      independent risk factors for both poor overall and lower limb survivals.
      CONCLUSION: The prevalence of big toenail opacity was high in hemodialysis
      patients. Despite the short observation period, our findings indicated that big
      toenail opacity had significant predictive power for poor overall and lower limb
      survival.

PMID- 29071508
TI  - Pharmacological Chaperones: Beyond Conformational Disorders.
AB  - Pharmacological chaperones (PCs) are small molecules that bind to nascent protein
      targets to facilitate their biogenesis. The ability of PCs to assist in the
      folding and subsequent forward trafficking of disease-causative protein
      misfolding mutants has opened new avenues for the treatment of conformational
      diseases such as cystic fibrosis and lysosomal storage disorders. In this
      chapter, an overview of the use of PCs for the treatment of conformational
      disorders is provided. Beyond the therapeutic application of PCs for the
      treatment of these disorders, pharmacological chaperoning of wild-type integral
      membrane proteins is discussed. Central to this discussion is the notion that the
      endoplasmic reticulum is a reservoir of viable but inefficiently processed wild
      type protein folding intermediates whose biogenesis can be facilitated by PCs to
      increase functional pools. To date, the potential therapeutic use of PCs to
      enhance the biogenesis of wild-type proteins has received little attention. Here
      the rationale for the development of PCs that target WT proteins is discussed.
      Also considered is the likelihood that some commonly used therapeutic agents may
      exert unrecognized pharmacological chaperoning activity on wild-type targets in
      patient populations.

PMID- 29071509
TI  - Toxins That Affect Voltage-Gated Sodium Channels.
AB  - Voltage-gated sodium channels (VGSCs) are critical in generation and conduction
      of electrical signals in multiple excitable tissues. Natural toxins, produced by
      animal, plant, and microorganisms, target VGSCs through diverse strategies
      developed over millions of years of evolutions. Studying of the diverse
      interaction between VGSC and VGSC-targeting toxins has been contributing to the
      increasing understanding of molecular structure and function, pharmacology, and
      drug development potential of VGSCs. This chapter aims to summarize some of the
      current views on the VGSC-toxin interaction based on the established receptor
      sites of VGSC for natural toxins.

PMID- 29071510
TI  - Heritable Skeletal Disorders Arising from Defects in Processing and Transport of
      Type I Procollagen from the ER: Perspectives on Possible Therapeutic Approaches.
AB  - Rare bone disorders are a heterogeneous group of diseases, initially associated
      with mutations in type I procollagen (PC) genes. Recent developments from
      dissection at the molecular and cellular level have expanded the list of disease
      causing proteins, revealing that disruption of the machinery that handles protein
      secretion can lead to failure in PC secretion and in several cases result in
      skeletal dysplasia. In parallel, cell-based in vitro studies of PC trafficking
      pathways offer clues to the identification of new disease candidate genes.
      Together, this raises the prospect of heritable bone disorders as a paradigm for
      biosynthetic protein traffic-related diseases, and an avenue through which
      therapeutic strategies can be explored.Here, we focus on human syndromes linked
      to defects in type I PC secretion with respect to the landscape of biosynthetic
      and protein transport steps within the early secretory pathway. We provide a
      perspective on possible therapeutic interventions for associated heritable
      craniofacial and skeletal disorders, considering different orders of complexity,
      from the cellular level by manipulation of proteostasis pathways to higher levels
      involving cell-based therapies for bone repair and regeneration.

PMID- 29071511
TI  - Folding Defects Leading to Primary Hyperoxaluria.
AB  - Protein misfolding is becoming one of the main mechanisms underlying inherited
      enzymatic deficits. This review is focused on primary hyperoxalurias, a group of
      disorders of glyoxylate detoxification associated with massive calcium oxalate
      deposition mainly in the kidneys. The most common and severe form, primary
      hyperoxaluria Type I, is due to the deficit of liver peroxisomal
      alanine/glyoxylate aminotransferase (AGT). Various studies performed in the last
      decade clearly evidence that many pathogenic missense mutations prevent the AGT
      correct folding, leading to various downstream effects including aggregation,
      increased degradation or mistargeting to mitochondria. Primary hyperoxaluria Type
      II and primary hyperoxaluria Type III are due to the deficit of glyoxylate
      reductase/hydroxypyruvate reductase (GRHPR) and 4-hydroxy-2-oxoglutarate aldolase
      (HOGA1), respectively. Although the molecular features of pathogenic variants of
      GRHPR and HOGA1 have not been investigated in detail, the data available suggest
      that some of them display folding defects. Thus, primary hyperoxalurias can be
      ranked among protein misfolding disorders, because in most cases the enzymatic
      deficit is due to the inability of each enzyme to reach its native and functional
      conformation. It follows that molecules able to improve the folding yield of the
      enzymes involved in each disease form could represent new therapeutic strategies.

PMID- 29071513
TI  - Xth EPR Workshop on Applications of EPR in Biology and Medicine.

PMID- 29071512
TI  - Similarities and Differences Between Migraine in Children and Adults:
      Presentation, Disability, and Response to Treatment.
AB  - PURPOSE OF REVIEW: This review presents findings from investigations of migraine
      in children and adults. Similarities and differences in the presentation, related
      consequences, and treatments between children and adults are reviewed. RECENT
      FINDINGS: Significant similarities exist in the presentation, disability, and
      treatments for migraine between children and adults. Despite such similarities,
      many adult migraine treatments adapted for use in children are not rigorously
      tested prior to becoming a part of routine care in youth. Existing research
      suggests that not all approaches are equally effective across age groups.
      Specifically, psychological treatments are shown to be somewhat less effective in
      adults than in children. Pharmacological interventions found to be statistically
      significant relative to placebo in adults may not be as effective in children and
      have the potential to present more risk than benefit when used in youth. The
      placebo effect in both children and adults is robust and is need of further
      study. Better understanding of treatment mechanisms for all interventions across
      the age spectrum is needed. Although migraine treatments determined to be
      effective for adults are frequently adapted for use in children with little
      evaluation prior to implementation, existing research suggests that this approach
      may not be the best practice. Adaptation of adult pharmacological treatment for
      use in youth may present a particular risk in comparison to benefits gained.
      Because of the known efficacy of psychological treatments, such as cognitive
      behavioral therapy, more universal use of these interventions should be
      considered, either as first-line treatment or in combination with pill-based
      therapies.

PMID- 29071514
TI  - [Destruction of the radial head : Endoprosthesis, autologous reconstruction or
      anconeus arthroplasty?]
AB  - BACKGROUND: Radiocapitellar arthritis or defects most often result from trauma.
      Most of the patients are young and have high functional demands with high load
      capacities. Therefore, endoprosthetic options should be postponed for as long as
      possible. If conservative treatment cannot relieve symptoms sufficiently, radial
      head preservation, resection or replacement options are at the surgeon's
      disposal. In early stages of radiocapitellar arthritis, radial head preservation
      options can be taken into account. The chances ofgood results decrease with
      increasing cartilage damage. TREATMENT OPTIONS: In addition to radial head
      preservation options this article discusses radial head resection with and
      without anconeus interposition and radial head as well as radiocapitellar
      replacement. Clinical data are rare. The advantages and disadvantages of each
      option must be discussed with the patient and the decision should be made
      individually on the basis of patient specific factors. The aim must be to
      postpone endoprosthetic options - especially total elbow arthroplasty - for as
      long as possible, while assuring a functional range of motion with an acceptable
      pain level.

PMID- 29071515
TI  - Systemic Inflammatory Response and Multiple Organ Dysfunctions Following Crush
      Injury: a New Experimental Model in Rabbits.
AB  - In this study, we aim to develop a new, reproducible crush injury (CI) model in
      rabbits. Anesthetized rabbits were compressed on both hind limbs using a special
      instrument for 6 h followed by 3 h of reperfusion. Blood samples and injured
      muscles were collected for biochemical analysis and morphological evaluation.
      Survival observation lasted for 72 h. Bilateral compressions with 10 kg/kg body
      weight (BW), but not with 5 kg/kg BW, reduced serious systemic impairment.
      Bilateral compressions with 10 kg/kg BW resulted in severe lactic acidosis;
      increased serum K+, creatine phosphokinase, aspartate transaminase, alanine
      transaminase, blood urea nitrogen, and creatinine levels; and a sharply decreased
      mean arterial blood pressure after compression release. Serious tissue edema and
      inflammation were observed in the damaged muscles. The mortality rates in
      compression groups were 20% (5 kg/kg BW) and 60% (10 kg/kg BW). There was a
      significant increase in plasma concentrations of TNF-alpha and IL-1beta after
      compression. Plasma IL-1beta levels returned to control levels at 6 h after
      compression release, whereas TNF-alpha peaked at 12 h following reperfusion.
      Furthermore, antiinflammatory cytokines, including IL-4 and IL-10, were also
      increased after compression, and these two cytokines peaked at 12 h after
      compression release. Our data suggested that bilateral compression with 10 kg/kg
      BW on rabbits' hind limbs is a reproducible CI model, and we also reported the CI
      induced systemic inflammatory responses and changes of cytokines over time.

PMID- 29071516
TI  - MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal
      cancer.
AB  - PURPOSE: The expression of miR-489 is linked to tumor development and
      progression; nevertheless, its role in tumor growth and invasion of colorectal
      cancer (CRC) and the underlying mechanism has not been clarified. EXPERIMENTAL
      DESIGN: We used quantitative RT-PCR to measure the expression of mature miR-489
      in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were
      predicted with TargetScan and substantiated by dual-luciferase reporter assay.
      Furthermore, we did in vitro and in vivo analysis with expression vectors and
      small interfering RNAs, to elucidate the precise role of miR-489 and its target
      gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion.
      RESULTS: Compared to the corresponding non-tumor tissues, miR-489 was frequently
      downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC
      recurrence free survival years in the group with elevated miR-489 expression than
      those with lower miR-489 expression. In addition, we examined that miR-489
      obviously inhibited the migratory and invasive capability in CRC. In further
      study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and
      downregulates its expression, and HDAC7 expression promoted tumor cell
      proliferation and invasion. We demonstrated that miR-489 suppresses tumor
      invasion and metastasis in CRC by targeting HDAC7. CONCLUSIONS: We identified
      that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The
      expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial
      light on how miR-489 functions in CRC pathogenesis.

PMID- 29071518
TI  - Cerebellum as a Master-Piece for Linguistic Predictability.

PMID- 29071517
TI  - Prognostic value of change in anti-thyroglobulin antibodies after thyroidectomy
      in patients with papillary thyroid carcinoma.
AB  - PURPOSE: Anti-thyroglobulin antibodies (TgAb) can be used as a surrogate tumor
      marker in the follow-up of papillary thyroid carcinoma (PTC). We try to determine
      if the change in TgAb levels in the first post-operative year is a good predictor
      of persistence/recurrence risk in TgAb-positive PTC patients. METHODS/PATIENTS:
      105 patients with PTC who underwent thyroidectomy between 1988 and 2014 were
      enrolled. We calculated the percentage of change in TgAb levels with the first
      measurement at 1-2 months after surgery and the second one at 12-14 months.
      RESULTS: TgAb negativization was observed in 29 patients (27.6%), a decrease of
      more than 50% was observed in 57 patients (54.3%), less than 50% in 12 patients
      (11.4%) and in 7 patients (6.7%) the TgAb level had increased. The percentage of
      persistence/recurrence was 0, 8.8, 16.7 and 71.4% in each group, respectively (p
      < 0.001). In the multivariate analysis, only the percentage of change in TgAb
      showed a significant association with the risk of persistence/recurrence,
      regardless of other factors such as age, size and TNM stages. CONCLUSIONS:
      Changes in TgAb levels in the first year after surgery can predict the risk of
      persistence/recurrence of TgAb-positive PTC patients. Patients who achieved
      negativization of TgAb presented an excellent prognosis.

PMID- 29071520
TI  - An Update on Masked Hypertension.
AB  - Masked hypertension refers to the phenomenon of having a non-elevated clinic
      blood pressure (BP) despite having an elevated out-of-clinic BP. Masked
      hypertension is a common phenotype with a cardiovascular risk profile similar to
      that of sustained hypertension, defined as elevated clinic and out-of-clinic BP.
      Current guidelines offer little guidance on the best practices for detecting and
      treating masked hypertension. This is in part due to insufficient evidence upon
      which to base recommendations as many questions remain regarding the optimal
      clinical management of masked hypertension. In this review, we will discuss the
      recent literature on masked hypertension related to disease prevalence,
      diagnosis, screening strategies, adverse outcomes, and treatment, and will
      highlight critical areas for future research.

PMID- 29071519
TI  - Preexposure Prophylaxis of HIV Infection: the Role of Clinical Practices in
      Ending the HIV Epidemic.
AB  - PURPOSE OF REVIEW: The aim of this study is to summarise the recent evidence from
      high-income settings about providers' ability to deliver on the UNAIDS goal of at
      least three million people at substantial risk of HIV infection with PrEP by
      2020, including awareness and knowledge about PrEP, willingness to prescribe
      PrEP, current levels of prescribing and service delivery models and issues.
      RECENT FINDINGS: Awareness about PrEP among health providers is growing, but at
      different pace depending on provider type. HIV and sexual health specialists are
      more likely to have knowledge about PrEP than generalists, and to be willing to
      prescribe it, mainly because of their closer contact with people at high risk for
      HIV and better risk assessment skills. There is still no consensus as to who
      should be responsible for providing PrEP, but clearly all hands on deck will be
      useful in delivering on the international target of three million people at
      substantial risk for HIV on PrEP by 2020. Only about 5% of the target has been
      reached so far. Local guidance and large-scale education and information programs
      for clinicians will be necessary to upskill health providers. High cost of PrEP
      is still a major barrier for its broad implementation, even in countries were
      PrEP roll-out has started. Health services are facing major structural challenges
      due to implementation of PrEP services to a substantial volume of patients. The
      early implementation experiences demonstrated that PrEP can be successfully
      delivered across a variety of settings, and a broad range of strategies and
      models of care can streamline PrEP delivery. Education of the providers and PrEP
      cost solutions will be essential for rapid roll-out of PrEP.

PMID- 29071521
TI  - CMR assessment and clinical outcomes of hypertrophic cardiomyopathy with or
      without ventricular remodeling in the end-stage phase.
AB  - End-stage phase of hypertrophic cardiomyopathy (ES-HCM) is a recognized part of
      HCM disease spectrum. Information on cardiac magnetic resonance (CMR) studies for
      ES-HCM especially for those without ventricular remodeling has been limited. We
      aimed to evaluate the morpho-functional and tissue features of ES-HCM with or
      without ventricular remodeling and to explore CMR prognostic value in these
      patients. We analysed CMR scans of sixty-three ES-HCM patients and divided them
      into those with ventricular dilatation (D-ES, n = 41) and those with normal
      ventricular size (N-ES, n = 22). Cox proportional hazards models were used to
      assess the association between CMR parameters and outcomes. Patients in D-ES
      showed hypokinetic-dilated HCM phenotype, while patients in N-ES showed
      hypokinetic-restrictive HCM phenotype. LGE extent was significantly larger in D
      ES (34.7% +/- 15.4% vs. 22.8% +/- 7.7%; P < 0.01). Atrial fibrillation and edema
      of lower extremity were more common in N-ES (72.7 vs. 29.3% and 54.5 vs. 24.4%,
      respectively; P < 0.05). Log-rank test found no significant difference between 2
      groups in combined end point of cardiovascular events (chi2 = 0.66, P = 0.418).
      In multivariate analysis, LGE (HR 1.57-1.83 per 10% LGE increase, P < 0.01) and
      indexed left atrial volume (LAVI) (HR 1.14-1.21 per 20 mL/m2 increase, P < 0.05)
      remained independently associated with combined end point when adjusted by other
      risk factors. The CMR features of HCM in end-stage span between two extremes. LGE
      is more extensive in those with ventricular remodeling and LAVI is larger in
      those with normal ventricular size. Both LGE and LAVI are significant predictors
      of poor outcomes.

PMID- 29071522
TI  - Elevated serum fetuin-A levels are associated with grades of retinopathy in type
      2 diabetic patients.
AB  - PURPOSE: Fetuin-A is a physiological inhibitor of insulin receptor tyrosine
      kinase and thus associated with insulin resistance, metabolic syndrome, and an
      increased risk for type 2 diabetes mellitus (T2DM). This study aims to
      investigate the possible relation between the serum fetuin-A levels and the
      stages of diabetic retinopathy (DR) in patients with T2DM. METHODS: This
      prospective study included 82 patients with T2DM and 19 age- and gender-matched
      healthy controls (HCs) (group 1). Diabetic patients were subclassified into three
      groups according to ocular findings: without DR (group 2; n = 26); non
      proliferative DR (group 3; n = 29), and proliferative DR (group 4; n = 27). Serum
      fetuin-A levels were determined by a spectrophotometric technique using an
      immulite chemiluminescent immunometric assay. The data were analyzed using a Mann
      Whitney U test, and the results were expressed as mean +/- standard deviation.
      RESULTS: Mean fetuin-A values were 256.4 +/- 21.3 MUg/ml in group 1, 263.5 +/-
      24.2 MUg/ml in group 2, 282.2 +/- 31.1 MUg/ml in group 3, and 296.3 +/- 26.2
      MUg/ml in group 4. Group 2 had higher mean fetuin-A level compared with group 1,
      but the difference was not statistically significant (p > 0.05). Serum fetuin-A
      levels were significantly higher in groups 3 and 4 compared with HCs (both p <
      0.05). Compared with group 2, both DR groups had higher fetuin-A levels with a
      significant difference (both p < 0.05); and patients with proliferative DR had
      significantly higher serum fetuin-A levels compared with non-proliferative DR (p
      < 0.05). The mean serum fetuin-A levels increased with the stage of DR, and the
      highest levels were found in patients with proliferative DR. CONCLUSION: Our
      findings suggest an association between fetuin-A levels and DR stage. In diabetic
      patients, the risk of retinopathy development increases with higher fetuin-A
      values. Fetuin-A may play an important role in the pathophysiology and
      progression of DR.

PMID- 29071523
TI  - Choroidal metastasis from non-small-cell lung cancer responsive to Osimertinib: a
      case report : Efficacy of a third-generation epidermal growth factor tyrosine
      kinase inhibitor.
AB  - PURPOSE: To report a case of a choroidal metastasis from a non-small-cell lung
      cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation, which
      responded to Osimertinib, a third-generation EGFR-tyrosine kinase inhibitor
      (TKI). BACKGROUND: First- and second-generation EGFR-TKis have been widely used
      for advanced NSCLC patients; however, acquired resistance to these inhibitors, as
      T790M mutation, could be present in resistant cases. Third-generation EGFR-TKis
      have emerged as potential therapeutics to overcome this resistance. METHODS: A 54
      year-old lady, affected by pulmonary adenocarcinoma with systemic metastases, was
      diagnosed with choroidal metastasis and since tumor biopsy was positive for the
      EGFR-T790M mutation, she was included in ASTRIS study, and she received 80 mg
      tablet of Osimertinib once a day. RESULTS: After a 2-week course of daily therapy
      with Osimertinib, the improvement of visual acuity was evident with the marked
      disappearance of visual field defects. We also report a dramatic anatomical
      reduction of choroidal mass on fundus examination and SD-OCT. These features
      remained stable at the 4-month follow-up visit. CONCLUSION: This report
      demonstrates that Osimertinib is effective for choroidal metastasis of NSCLC
      harboring an EGFR-T790M mutation, which has progressed on or after first- or
      second-generation EGFR-TKI therapy.

PMID- 29071525
TI  - The Primacy of Patient-Centered Outcomes in Tracheostomy Care.

PMID- 29071524
TI  - Symptom Monitoring in Pediatric Oncology Using Patient-Reported Outcomes: Why,
      How, and Where Next.
AB  - Symptom monitoring using patient-reported outcomes (PROs) is not common in
      pediatric oncology, despite interest from stakeholders-including patients,
      families, clinicians, and regulatory organizations-and proven clinical benefit in
      adult oncology. This article examines the foundational data for patient-reported
      symptom reporting in this population and posits the next investigative steps
      toward the implementation of patient-reported symptom monitoring in the care and
      research of pediatric oncology patients. The reasoning behind, and feasibility
      of, monitoring symptoms in pediatric oncology patients using PRO measures are
      discussed, as well as specific tools that have been developed to track symptoms
      in this population, including innovative electronic self-reporting platforms
      built to engage children in the symptom reporting process. Aspects of engaging
      both patients and clinicians in the symptom self-report process are reviewed, as
      are the experiences of "early adopters" of this process in pediatric oncology and
      across pediatrics. It is clear that there are key issues that remain regarding
      the use of PROs for symptom monitoring, including selection of specific outcomes
      to monitor, how to resolve discrepant reports, and determination of benefit. The
      next steps for investigation of these issues are discussed. Unanswered questions
      notwithstanding, work should continue to make patient-reported symptom monitoring
      an established, evidence-based part of routine and research practice in pediatric
      oncology.

PMID- 29071526
TI  - The ubiquitin-proteasome pathway in adult and pediatric brain tumors: biological
      insights and therapeutic opportunities.
AB  - Nearly 20 years ago, the concept of targeting the proteasome for cancer therapy
      began gaining momentum. This concept was driven by increased understanding of the
      biology/structure and function of the 26S proteasome, insight into the role of
      the proteasome in transformed cells, and the synthesis of pharmacological
      inhibitors with clinically favorable features. Subsequent in vitro, in vivo, and
      clinical testing culminated in the FDA approval of three proteasome inhibitors
      bortezomib, carfilzomib, and ixazomib -for specific hematological malignancies.
      However, despite in vitro and in vivo studies pointing towards efficacy in solid
      tumors, clinical responses broadly have been evasive. For brain tumors, a
      malignancy in dire need of new approaches both in adult and pediatric patients,
      this has also been the case. Elucidation of proteasome-dependent processes in
      specific types of brain tumors, the evolution of newer proteasome targeting
      strategies, and the use of proteasome inhibitors in combination strategies will
      clarify how these agents can be leveraged more effectively to treat central
      nervous system malignancies. Since brain tumors represent a heterogeneous subset
      of solid tumors, and in particular, pediatric brain tumors possess distinct
      biology from adult brain tumors, tailoring of proteasome inhibitor-based
      strategies to specific subtypes of these tumors will be critical for advancing
      care for affected patients, and will be discussed in this review.

PMID- 29071528
TI  - Should We Ignore What We Cannot Measure? How Non-Uniform Stretch, Non-Uniform
      Wall Thickness and Minor Side Branches Affect Computational Aortic Biomechanics
      in Mice.
AB  - In order to advance the state-of-the-art in computational aortic biomechanics, we
      investigated the influence of (i) a non-uniform wall thickness, (ii) minor aortic
      side branches and (iii) a non-uniform axial stretch distribution on the location
      of predicted hotspots of principal strain in a mouse model for dissecting
      aneurysms. After 3 days of angiotensin II infusion, a murine abdominal aorta was
      scanned in vivo with contrast-enhanced micro-CT. The animal was subsequently
      sacrificed and its aorta was scanned ex vivo with phase-contrast X-ray
      tomographic microscopy (PCXTM). An automatic morphing framework was developed to
      map the non-pressurized, non-stretched PCXTM geometry onto the pressurized,
      stretched micro-CT geometry. The output of the morphing model was a structural
      FEM simulation where the output strain distribution represents an estimation of
      the wall deformation, not only due to the pressurization, but also due to the
      local axial stretch field. The morphing model also included minor branches and a
      mouse-specific wall thickness. A sensitivity study was then performed to assess
      the influence of each of these novel features on the outcome of the simulations.
      The results were supported by comparing the computed hotspots of principal strain
      to hotspots of early vascular damage as detected on PCXTM. Non-uniform axial
      stretch, non-uniform wall thickness and minor subcostal arteries significantly
      alter the locations of calculated hotspots of maximal principal strain. Even if
      experimental data on these features are often not available in clinical practice,
      one should be aware of the important implications that simplifications in the
      model might have on the final simulated result.

PMID- 29071529
TI  - Beat-by-Beat Estimation of the Left Ventricular Pressure-Volume Loop Under
      Clinical Conditions.
AB  - This paper develops a method for the minimally invasive, beat-by-beat estimation
      of the left ventricular pressure-volume loop. This method estimates the left
      ventricular pressure and volume waveforms that make up the pressure-volume loop
      using clinically available inputs supported by a short, baseline echocardiography
      reading. Validation was performed across 142,169 heartbeats of data from 11
      Pietrain pigs subject to two distinct protocols encompassing sepsis, dobutamine
      administration and clinical interventions. The method effectively located
      pressure-volume loops, with low overall median errors in end-diastolic volume of
      8.6%, end-systolic volume of 17.3%, systolic pressure of 19.4% and diastolic
      pressure of 6.5%. The method further demonstrated a low overall mean error of
      23.2% predicting resulting stroke work, and high correlation coefficients along
      with a high percentage of trend compass 'in band' performance tracking changes in
      stroke work as patient condition varied. This set of results forms a body of
      evidence for the potential clinical utility of the method. While further
      validation in humans is required, the method has the potential to aid in clinical
      decision making across a range of clinical interventions and disease state
      disturbances by providing real-time, beat-to-beat, patient specific information
      at the intensive care unit bedside without requiring additional invasive
      instrumentation.

PMID- 29071530
TI  - Evolutionary relationships between seryl-histidine dipeptide and modern serine
      proteases from the analysis based on mass spectrometry and bioinformatics.
AB  - Seryl-histidine dipeptide (Ser-His) has been recognized as the shortest peptide
      with hydrolysis cleavage activity; however, its protein cleavage spectrum has not
      yet been fully explored. Here, four differently folded proteins were treated with
      Ser-His, and the digestion products were evaluated with high-resolution mass
      spectrometry. The cleavage efficiency and cleavage propensity of Ser-His against
      these protein substrates were calculated at both the primary and secondary
      sequence levels. The above experiments show that Ser-His cleaves a broad spectrum
      of substrate proteins of varying secondary structures. Moreover, Ser-His could
      cleave at all 20 amino acids with different efficiencies according to the
      protein, which means that Ser-His has the original digestion function of serine
      proteases. Furthermore, we collected and compared the catalytic sites and
      cleavage sites of 340 extant serine proteases derived from 17 representative
      organisms. A consensus motif Ser-[X]-His was identified as the major pattern at
      the catalytic sites of serine proteases from all of the organisms represented
      except Danio rerio, which uses Ser-Lys instead. This finding indicates that Ser
      His is the core component of the serine protease catalytic site. Moreover, our
      analysis revealed that the cleavage sites of modern serine proteases have become
      more specific over the evolutionary history of this family. Based on the above
      analysis results, it could be found that Ser-His is likely the original serine
      protease and maybe the evolutionary core of modern serine proteases.

PMID- 29071531
TI  - Structural complexity and functional diversity of plant NADPH oxidases.
AB  - Plant NADPH oxidases also known as respiratory burst oxidase homologs (Rbohs) are
      a family of membrane-bound enzymes that play diverse roles in the defense
      response and morphogenetic processes via regulated generation of reactive oxygen
      species. Rbohs are associated with a variety of functions, although the reason
      for this is not clear. To evaluate using bioinformatics, the possible mechanisms
      for the observed functional diversity within the plant kingdom, 127 Rboh protein
      sequences representing 26 plant species were analyzed. Multiple clusters were
      identified with gene duplications that were both dicot as well as monocot
      specific. The N-terminal sequences were observed to be highly variable. The
      conserved cysteine (equivalent of Cys890) in C-terminal of AtRbohD suggested that
      the redox-based modification like S-nitrosylation may regulate the activity of
      other Rbohs. Three-dimensional models corresponding to the N-terminal domain for
      Rbohs from Arabidopsis thaliana and Oryza sativa were constructed and molecular
      dynamics studies were carried out to study the role of Ca2+ in the folding of
      Rboh proteins. Certain mutations indicated possibly affect the structure and
      function of the plant NADPH oxidases, thereby providing the rationale for further
      experimental validation.

PMID- 29071532
TI  - Comment on 'Association between serum osteocalcin and body mass index: a
      systematic review and meta-analysis.'

PMID- 29071527
TI  - (Immuno)proteasomes as therapeutic target in acute leukemia.
AB  - The clinical efficacy of proteasome inhibitors in the treatment of multiple
      myeloma has encouraged application of proteasome inhibitor containing therapeutic
      interventions in (pediatric) acute leukemia. Here, we summarize the positioning
      of bortezomib, as first-generation proteasome inhibitor, and second-generation
      proteasome inhibitors in leukemia treatment from a preclinical and clinical
      perspective. Potential markers for proteasome inhibitor sensitivity and/or
      resistance emerging from leukemia cell line models and clinical sample studies
      will be discussed focusing on the role of immunoproteasome and constitutive
      proteasome (subunit) expression, PSMB5 mutations, and alternative mechanisms of
      overcoming proteolytic stress.

PMID- 29071533
TI  - Correction to: Understanding the Therapist Contribution to Psychotherapy Outcome:
      A Meta-Analytic Approach.

PMID- 29071534
TI  - Effect of Scopolamine on Mice Motor Activity, Lick Behavior and Reversal Learning
      in the IntelliCage.
AB  - Automated homecage monitoring systems are now widely recognized and used tools in
      cognitive neuroscience. However, few of these studies cover pharmacological
      interventions. Scopolamine, an anticholinergic memory disrupting agent is
      frequently used to study learning behavior. We studied the impact of scopolamine
      treatment in a relevant dose-range on activity, drinking behavior and reversal
      learning of C57BL/DJ mice in a homecage-like, social environment, using the
      IntelliCage. Naive mice were first habituated to the IntelliCage, where they
      learned to nosepoke in any of the four corners in order to gain access to the
      water reward. Visits, nosepokes, lick numbers and durations were recorded. Mice
      were then trained to distinguish between a rewarded correct corner and punished,
      incorrect corners. Later, in the reversal learning phase, the assigned correct
      corner was rotated clockwise every 24 h. Upon s.c. administration of scopolamine
      general activity represented by visit and nosepoke numbers increased, but their
      durations were shorter. Surprisingly, general activity and lick behavior were
      drastically altered. Scopolamine also significantly reduced the ability to
      perform a reversal learning task. We not only found significant decline in
      reversal learning due to scopolamine treatment, but studied the method specific
      underlying behaviors: the general activity and lick behavior as well.

PMID- 29071535
TI  - Cure kinetic study of methacrylate-POSS copolymers for ocular lens.
AB  - The physical, mechanical and biological properties of multicomponent acrylate
      based hard lenses are directly influenced by degree of conversion achieved during
      copolymerization. In this research, polyhedral oligomeric silsesquioxane (POSS)
      acrylate is introduced into the polymer backbone in combination with hydroxyethyl
      methacrylate, dimethyl itaconate, methyl methacrylate, 3-(trimethoxysilyl) propyl
      methacrylate and triethylene glycol dimethacrylate in free-radical bulk
      polymerization. Kinetics of curing process was investigated by two techniques:
      differential scanning calorimetry and FTIR spectroscopy. Reaction kinetics in
      free-radical bulk polymerization of the system was studied by isothermal DSC
      performed at 65, 75, 85, and 95  degrees C using different quantities of
      initiator. Three compounds were prepared in different concentrations (0.2, 0.4
      and 0.6 mol%) of 2,2'-azobisisobutyronitrile as initiator. Conversion rate was
      calculated as a function of time using data obtained from DSC measurements. The
      kinetic parameters of the reaction such as reaction constants, reaction orders
      and activation energies were obtained from the isothermal DSC data according to
      the autocatalytic model developed by Kamal and Sourour. The results showed that
      the experimental values were in good agreement with theoretically estimated
      values and our results may suggest that the polymerization reaction of this
      system is well described by Kamal's model. Cytotoxicity results, performed on
      extracts 28 days after PBS incubation, showed no toxicity of the materials
      extracted from the lenses indicating that they can be considered as safe
      materials in ocular lens applications. The viability and proliferation of L929
      fibroblast cells in extracting media were followed by 3-[4,5-dimethylthiazol-2
      yl]-2,5-diphenyltetrazolium bromide (MTT) and they may have a great potential as
      ideal supporting lens in people who suffer from keratoconus disease.

PMID- 29071536
TI  - Cytotoxicity of silver and copper nanoparticles on rainbow trout (Oncorhynchus
      mykiss) hepatocytes.
AB  - Nanoparticles are commonly used in the industry and are present in consumer
      goods; therefore, evaluation of their potential toxicity is necessary. The aim of
      the present study was to assess the cytotoxic effects of the nanoparticles of
      silver (AgNPs) at the concentration of 1.5 mg L-1 and copper (CuNPs) at 0.15 mg L
      1 on rainbow trout (Oncorhynchus mykiss) hepatocytes after 28 days of exposure.
      Histological analysis revealed dilated sinusoids, shrunken hepatocytes, nuclear
      necrosis, and increased number of Kupffer cells in the liver of fish exposed to
      nanoparticles. The lowest hepatocyte proliferation index was observed in fish
      treated with AgNPs. Ultrastructural studies revealed mitochondrial edema and
      cristolysis, dilated and loosened endoplasmic reticulum, cytoplasm vacuolation,
      accumulation of lipid droplets, glycogen depletion, and formation of myelin-like
      bodies. The results also revealed that the liver of fish exposed to copper
      nanoparticles showed higher regenerative potential indicated by higher
      proliferation index, more abundant glycogen, and more numerous Kupffer cells
      compared to the fish treated with silver nanoparticles.

PMID- 29071537
TI  - Major Gastric Haemorrhage After Intragastric Balloon Insertion: Case Report.
AB  - Intragastric balloons are a minimally invasive option for weight loss. They are
      generally well tolerated and rarely associated with serious adverse events. We
      report a case of major upper gastrointestinal haemorrhage after insertion of an
      Orbera(r) intragastric balloon.

PMID- 29071538
TI  - Total flavone of Desmodium styracifolium relieved apoptosis and autophagy of COM
      induced HK-2 cells by regulating KIM-1 via p38/MAPK pathway.
AB  - The purpose of the study was to investigate the mechanism of total flavone of
      Desmodium styracifolium (TFDS) in regulating the formation of urinary calculi.
      Protein levels of KIM-1, LC3-II, p-p38 were measured by Western blot. The effect
      of different COM concentrations, different TFDS concentrations, SB203580
      (specific inhibitor of p38/MAPK), and overexpression of KIM-1 on cell viability
      were detected by WST-1 assay. The apoptotic cells and FITC positive cells were
      detected by flow cytometry. HK-2 cell viability decreased with the increase of
      COM concentration, and the protein levels of KIM-1, LC3-II, and p-p38 increased
      with the time. Blocking the p38/MAPK pathway or co-cultured with TFDS inhibited
      the effects of COM on apoptosis and autophagy of HK-2 cells. In addition,
      blocking the p38/MAPK pathway inhibited the expression of KIM-1. In COM-induced
      cells, after treated with SB203580, overexpression of KIM-1 could reverse the
      protection effect of SB203580 on COM-induced cell damage and the inhibition of
      SB203580 on COM-induced excessive autophagy, suggesting p38/MAPK regulated KIM-1
      to regulate COM-induced cell apoptosis and autophagy. Finally, we proved that
      TFDS inhibited p38/MAPK pathway. And the protection effect of COM-induced cell
      injury increased with the increase of TFDS concentration, and the adhesion
      between COM and cells decreased with the increase of TFDS concentration. With the
      increase of the concentration of TFDS, p38/MAPK pathway was gradually inhibited,
      and KIM-1 and autophagy related proteins were decreased. TFDS inhibited HK-2 cell
      apoptosis and autophagy by regulating KIM-1 via p38/MAPK pathway.

PMID- 29071539
TI  - Knockdown of IARS2 suppressed growth of gastric cancer cells by regulating the
      phosphorylation of cell cycle-related proteins.
AB  - The purpose of the article is to investigate the role of IARS2 in proliferation,
      apoptosis, and cell cycle of gastric cancer (GC) cells in vitro. The IARS2-shRNA
      lentiviral vector was established and used to infect the GC cell line AGS. qRT
      PCR and Western blot were employed to determine the efficiency of IARS2
      knockdown. The effects of IARS2 knockdown on cell proliferation, cell clone
      formation, and cell cycle were assessed by MTT assay, colony formation assay, and
      flow cytometer analysis, respectively. Finally, a PathScan Antibody Array Kit was
      used to detect the expression levels of cell cycle-related proteins after IARS2
      knockdown in AGS cells to elucidate the underlying mechanisms. Compared with
      negative control group, IARS2 was significantly knocked down by transfection with
      lentivirus encoding shRNA of IARS2 in AGS cells. IARS2 knockdown significantly
      inhibited the proliferation and colony formation ability and induced cycle arrest
      at G2/M phase of AGS cells. IARS2 knockdown significantly decreased the
      expression levels of phosphorylation of (p-Smad2), p-SAPK/JUK, cleavage-Caspase
      7, and p-TAK1, but increased the expression levels of p-53 and cleavage-PARP in
      AGS cells compared to shCtrl group. We demonstrated that IARS2 knockdown inhibits
      proliferation, suppresses colony formation, and causes cell cycle arrest in AGS
      cells. We also found that IARS2 regulates key molecules of cell apoptosis-related
      signaling pathway.

PMID- 29071540
TI  - Current and emerging treatment strategies for children with progressive
      chiasmatic-hypothalamic glioma diagnosed as infants: a web-based survey.
AB  - Treatment of infant hypothalamic chiasmatic glioma (iCHG) is challenging, about
      30% of the children progress during chemotherapy. Despite subsequent treatments
      the 5 year overall-survival rate is only 70%. This study investigates treatment
      strategies currently applied for progressive iCHG. A web-based questionnaire was
      sent out to the members of the SIOPE Brain Tumour Group asking for current second
      and third line strategies at progression during and after the end of first line
      therapy. The questionnaire was answered by 47 paediatric oncologists from 15
      countries. iCHG progressing during first line therapy with carboplatin
      vincristine would be considered for treatment with alternative chemotherapy by 17
      (36%) and with surgery plus chemotherapy by 27 respondents (58%). Components
      suggested for second line were vinblastine (62%), cisplatin (34%) and
      cyclophosphamide (26%). For third line therapy bevacizumab (BVZ) was considered
      as suitable by respondents in 53% (often with irinotecan 40%) and vinblastine by
      34% respectively. Experience with BVZ in CHG is shown by 53% of respondents
      regarding at least 95 patients (median treated 1-5 patients per respondent at any
      age) with a median BVZ administration over 12 months. Effectiveness was reported
      varying between stable disease and regression while complications were rarely
      stated (proteinuria, hypertension, bleeding). BVZ would be available to 85% of
      respondents as therapeutic option for iCHG patients. Multiple anti-neoplastic
      drug regimens are applied for progressive iCHG, partly considered in combination
      with surgery if safely feasible. BVZ is commonly used at a satisfactory level in
      third line, mainly combined with irinotecan.

PMID- 29071541
TI  - Nutrient drink test: Normative values in Indian children.
AB  - BACKGROUND: Nutrient drink test (NDT) is a simple, non-invasive method to assess
      gastric function including accommodation. However, data on normal satiety drink
      volume (SDV) in children is scanty with no information about postprandial
      symptoms (PPS). Our aims were to establish normal values of NDT in healthy
      children and evaluate its correlation with age, gender, and anthropometry.
      METHODS: Six- to 18-year-old healthy children underwent the NDT. The nutrient
      drink (0.94 kcal/mL) was given at a constant rate of 15 mL/min in 6-12-year-old
      subjects and at 30 mL/min in 13-18-year-old subjects till satiety score of 5 was
      reached. Postprandial symptoms (30 min) of fullness, nausea, bloating, and pain
      were scored using a visual analogue scale (0-100 mm) individually and as
      aggregate score. RESULTS: Sixty-seven children (40 boys, age 12 [6-18 years])
      were enrolled. Median SDV was 360 [180-960 mL], higher in 13-18-year-olds in
      comparison to 6-12-year-old children (360 [240-1002] vs. 300 [148-960] mL;
      p=0.005). SDV showed significant correlation with age, weight, and height. SDV
      was higher in boys than girls (450 [240-1074] vs. 330 [240-480] mL; p=0.02) in
      the older children (13-18 y), but it was similar in the younger children. Mild
      fullness (40 [0-80]) was the only PPS seen in 85% children and none had pain. PPS
      were not different between boys and girls or younger and older children.
      CONCLUSION: The study provides normative data of SDV and PPS by NDT in 6-18-year
      old children. SDV correlated with age and was higher in adolescent boys than
      girls.

PMID- 29071542
TI  - Infant with hepatomegaly and hypoglycemia: A setting for fatty acid oxidation
      defects.
AB  - Fatty acid oxidation defects (FAOD) are one of the commonest metabolic liver
      diseases (MLDs) that can have varied presentations in different age groups. An
      infant presented with short history of jaundice and irritability, examination
      showed soft hepatomegaly. Investigations revealed non-ketotic hypoglycemia
      suggesting FAOD which was later confirmed as carnitine uptake defect with gas
      chromatography and mass spectrometry and mutation analysis. Patient improved with
      acute management of metabolic crisis, carnitine supplementation and corn starch
      therapy with reversal of encephalopathy, reduction in hepatomegaly, maintenance
      of euglycemia and improvement in liver function tests and creatine phosphokinase
      on follow up. Non-ketotic hypoglycemia is a characteristic finding in FAODs.
      Early diagnosis and appropriate management can result in excellent outcomes in
      patients with FAODs.

PMID- 29071543
TI  - A Comparison of Masculinity Facial Preference Among Naturally Cycling, Pregnant,
      Lactating, and Post-Menopausal Women.
AB  - Women show cyclical shifts in preferences for physical male traits. Here we
      investigated how fertility status influences women's facial masculinity
      preference in men by analyzing a large sample of heterosexual women (N = 3720).
      Women were regularly either cycling (in both low- and high-conception probability
      groups), lactating or were currently in a non-fertile state (pregnant or post
      menopausal). Analyses simultaneously controlled for women's age and sexual
      openness. Participants via two alternative forced choice questions judged
      attractiveness of masculinized and feminized men's faces. After controlling for
      the effect of age and sociosexuality, regularly cycling and pregnant women showed
      a stronger preference for masculinity than lactating and post-menopausal women.
      However, there was no significant difference in masculinity preference between
      women in the low- and high-conception probability groups. Women's sociosexuality
      showed a positive, but very weak association with men's facial masculinity
      preference. We suggest that women's overall, long-term hormonal state (cycling,
      post-menopausal) is a stronger predictor of preference for sexual dimorphism than
      changes in hormonal levels through the cycle.

PMID- 29071544
TI  - Masculine Voices Predict Well-Being in Female-to-Male Transgender Individuals.
AB  - Voices convey important social information about an individual's identity,
      including gender. This is especially relevant to transgender individuals, who
      cite voice alteration as a primary goal of the gender alignment process. Although
      the voice is a primary target of testosterone therapy among female-to-male (FTM)
      trans people, little research has explored the effects of such changes on their
      psychological well-being. Here, we investigated how FTMs' vocal gender related to
      their well-being. A total of 77 FTMs (M age = 25.45 years, SD = 6.77) provided
      voice samples and completed measures of their well-being and psychological
      health. An independent group of 32 naive raters (M age = 22.16 years, SD = 8.21)
      subsequently rated the voice samples for masculinity. We found that FTMs whose
      voices sounded more congruent with their experienced gender (i.e., sounded more
      masculine) reported greater well-being (better life satisfaction, quality of
      life, and self-esteem; lower levels of anxiety and depression) than FTMs with
      less gender congruent (i.e., more feminine) voices (beta = .48). The convergence
      between outwardly perceived vocal gender and gender identity brought about
      through hormone replacement therapy may therefore support greater well-being for
      FTMs.

PMID- 29071545
TI  - Volvivity, Femininity, Fraternity: Breaching the Sexual Orientation Fortress.

PMID- 29071546
TI  - Associations Between Croatian Adolescents' Use of Sexually Explicit Material and
      Sexual Behavior: Does Parental Monitoring Play a Role?
AB  - The use of sexually explicit material (SEM) has become a part of adolescent
      sexual socialization, at least in the Western world. Adolescent and young
      people's SEM use has been associated with risky sexual behaviors, which has
      recently resulted in policy debates about restricting access to SEM. Such
      development seems to suggest a crisis of the preventive role of parental
      oversight. Based on the Differential Susceptibility to Media Effects Model, this
      study assessed the role of parental monitoring in the context of adolescent
      vulnerability to SEM-associated risky or potentially adverse outcomes (sexual
      activity, sexual aggressiveness, and sexting). Using an online sample of Croatian
      16-year-olds (N = 1265) and structural equation modeling approach, parental
      monitoring was found consistently and negatively related to the problematic
      behavioral outcomes, regardless of participants' gender. While SEM use was
      related to sexual experience and sexting, higher levels of parental monitoring
      were associated with less frequent SEM use and lower acceptance of sexual
      permissiveness. Despite parents' fears about losing the ability to monitor their
      adolescent children's lives in the Internet era, there is evidence that parental
      engagement remains an important protective factor.

PMID- 29071547
TI  - Symposia in undergraduate medical education: tailoring training in competencies
      to students' needs.
AB  - INTRODUCTION: In mastering competencies, it is a challenge to create training
      sessions which acknowledge individual students' needs and are logistically
      feasible in the medical master's program. METHODS: Symposia were implemented in
      the medical master's program to provide knowledge and training of skills in a
      number of topics, providing a positive contribution to students' competencies and
      personal development. Each symposium contained a morning and afternoon program,
      structured around medical and societal themes addressing various competencies and
      covering current national and international events. Alternating interactive
      teaching methods were used. Students were asked to rate each daypart program on a
      5-point Likert scale in terms of both teaching methods and content, and to
      comment on the best aspects of the symposium as well as areas for improvement.
      Scores higher than 3.5 were interpreted as a predominantly favourable outcome.
      RESULTS: In 2016, 10 symposia were organized with an average of 108 attendees and
      a response rate of 63% (1,366 completed questionnaires). Mean overall scores on
      'teaching methods' and 'usefulness for professional development' were 3.8 and
      3.7, respectively. The overall results corresponded with a high level of student
      appreciation. CONCLUSION: Symposia offer a podium for training students in
      subject matter and competencies that is greatly appreciated. Using alternating
      interactive teaching methods, symposia are structured around medical and societal
      themes and adjusted to the latest developments and current events in healthcare.
      By allowing students to select the symposia they would like to participate in, a
      tailor-made medical master's program in competencies is created.

PMID- 29071548
TI  - Are differences between groups different at different occasions?

PMID- 29071549
TI  - Predatory publishers and fraudulent conferences: Perspectives and implications
      for novice researchers.

PMID- 29071550
TI  - To fail is human: remediating remediation in medical education.
AB  - INTRODUCTION: Remediating failing medical learners has traditionally been a craft
      activity responding to individual learner and remediator circumstances. Although
      there have been moves towards more systematic approaches to remediation (at least
      at the institutional level), these changes have tended to focus on due process
      and defensibility rather than on educational principles. As remediation practice
      evolves, there is a growing need for common theoretical and systems-based
      perspectives to guide this work. METHODS: This paper steps back from the
      practicalities of remediation practice to take a critical systems perspective on
      remediation in contemporary medical education. In doing so, the authors
      acknowledge the complex interactions between institutional, professional, and
      societal forces that are both facilitators of and barriers to effective
      remediation practices. RESULTS: The authors propose a model that situates
      remediation within the contexts of society as a whole, the medical profession,
      and medical education institutions. They also outline a number of recommendations
      to constructively align remediation principles and practices, support a continuum
      of remediation practices, destigmatize remediation, and develop institutional
      communities of practice in remediation. DISCUSSION: Medical educators must
      embrace a responsible and accountable systems-level approach to remediation if
      they are to meet their obligations to provide a safe and effective physician
      workforce.

PMID- 29071551
TI  - Toxicological Assessment and UV/TiO2-Based Induced Degradation Profile of
      Reactive Black 5 Dye.
AB  - In this study, the toxicological and degradation profile of Reactive Black 5
      (RB5) dye was evaluated using a UV/TiO2-based degradation system. Fourier
      transform infrared spectroscopy (FT-IR), thin layer chromatography (TLC), high
      performance liquid chromatography (HPLC) and ultra-performance liquid
      chromatography coupled with mass spectrometry (UPLC-MS) techniques were used to
      evaluate the degradation level of RB5. The UV-Vis spectral analysis revealed the
      disappearance of peak intensity at 599 nm (lambdamax). The FT-IR spectrum of
      UV/TiO2 treated dye sample manifest appearance of new peaks mainly because of the
      degraded product and/or disappearance of some characteristics peaks which were
      present in the untreated spectrum. The HPLC profile verified the RB5 degradation
      subject to the formation of metabolites at different retention times. A stable
      color removal higher than 96% with COD removal in the range of 74-82.3% was noted
      at all evaluated dye concentrations. The tentative degradation pathway of RB5 is
      proposed following a careful analysis of the intermediates identified by UPLC-MS.
      Toxicity profile of untreated and degraded dye samples was monitored using three
      types of human cell lines via MTT assay and acute toxicity testing with Artemia
      salina. In conclusion, the UV/TiO2-based degradation system could be effectively
      employed for the remediation of textile wastewater comprising a high
      concentration of reactive dyes.

PMID- 29071552
TI  - Paths to Change: Bio-Economic Factors, Geographical Gradients and the Land-Use
      Structure of Italy.
AB  - This study introduces a bio-economic approach to evaluate the influence of local
      socioeconomic contexts on complex processes of landscape transformation
      (urbanization, withdrawal of farming with woodland creation and loss in crop
      mosaics) in a sustainable development perspective. Land-use and socioeconomic
      indicators (including shares of agriculture, industry and services in total
      product, per-worker value added, productivity by economic sector, distance from
      central cities, latitude and elevation) at the local district scale in Italy have
      been considered together in an exploratory approach based on multivariate
      statistics. The combined use of land-use and socioeconomic indicators was
      preferred to more traditional approaches based on single-variable analysis and
      allows identifying latent factors of landscape transformation at the local scale.
      Our approach sheds light in the intimate relationship between regional economic
      structures and land-use change in districts with varying socio-environmental
      attributes across Italy. Urban-rural divides, coastal-inland dichotomy and the
      elevation gradient were relevant factors shaping urbanization-driven landscape
      transformations at the country scale. Indicators of economic structure (and
      especially industrial production and per-worker productivity of industry and
      services) were also documented to influence greatly entity and direction of
      change in the use of land. Discontinuous and dispersed urbanization has been
      demonstrated to be spatially-decoupled from consolidated (continuous and compact)
      urbanization, expanding into undeveloped rural areas progressively far away from
      central cities and being spatially associated with forest land.

PMID- 29071553
TI  - Analysis of the Governance Structures in Japan's Biosphere Reserves: Perspectives
      from Bottom-Up and Multilevel Characteristics.
AB  - This paper analyzes the governance structures of Biosphere Reserves (BRs) in
      Japan by focusing on six criteria that elucidate the main characteristics
      therein: general information (nomination process, year of designation, size, and
      population), legal frameworks, stakeholder identification, and decision-making
      processes (number of municipalities and role of consociation), administrative
      institutions (human resources, budgetary situation, and expense distribution),
      executed BR implementation activities, and participatory/collaborative
      frameworks. This research consists of a literature review, a questionnaire
      administered to the secretariats of seven existing BRs and follow-up interviews.
      Three main characteristics of BRs were identified. First, a responsible local
      government(s) is nominated to manage the BR rather than the central government.
      Consequently, BR implementation in Japan is led by those municipalities that have
      strong motivations for regional development using the BR concept. Second, two
      types of BR governance structures exist in Japan: the single municipality type
      and the multi-municipality type. All BRs have so called Kyougikai, a consociation
      for decision-making, consultation and/or collaboration among stakeholders. In the
      single municipality structure, the consociation includes diverse actors from
      private and community sectors, while in the multi-municipality structure,
      consociations are based in more diplomatic settings and only include members of
      the public sector. Third, gaps between pre/post-Seville BR implementation sites
      were identified. The motivations for the formation of pre-Seville BRs, which were
      designated in 1980 in a top-down fashion prior to an awareness of BRs, varied
      greatly from those BRs nominated by municipalities after 2010. The authors
      identified fewer administrative resources and activities associated with the pre
      Seville sites.

PMID- 29071555
TI  - Use of near-infrared spectroscopy (NIRs) in the biopharmaceutical industry for
      real-time determination of critical process parameters and integration of
      advanced feedback control strategies using MIDUS control.
AB  - Control of biopharmaceutical processes is critical to achieve consistent product
      quality. The most challenging unit operation to control is cell growth in
      bioreactors due to the exquisitely sensitive and complex nature of the cells that
      are converting raw materials into new cells and products. Current monitoring
      capabilities are increasing, however, the main challenge is now becoming the
      ability to use the data generated in an effective manner. There are a number of
      contributors to this challenge including integration of different monitoring
      systems as well as the functionality to perform data analytics in real-time to
      generate process knowledge and understanding. In addition, there is a lack of
      ability to easily generate strategies and close the loop to feedback into the
      process for advanced process control (APC). The current research aims to
      demonstrate the use of advanced monitoring tools along with data analytics to
      generate process understanding in an Escherichia coli fermentation process. NIR
      spectroscopy was used to measure glucose and critical amino acids in real-time to
      help in determining the root cause of failures associated with different lots of
      yeast extract. First, scale-down of the process was required to execute a simple
      design of experiment, followed by scale-up to build NIR models as well as soft
      sensors for advanced process control. In addition, the research demonstrates the
      potential for a novel platform technology that enables manufacturers to
      consistently achieve "goldenbatch" performance through monitoring, integration,
      data analytics, understanding, strategy design and control (MIDUS control). MIDUS
      control was employed to increase batch-to-batch consistency in final product
      titers, decrease the coefficient of variability from 8.49 to 1.16%, predict
      possible exhaust filter failures and close the loop to prevent their occurrence
      and avoid lost batches.

PMID- 29071554
TI  - Inhibitory Effect of Vaginal Lactobacillus Supernatants on Cervical Cancer Cells.
AB  - Lactobacilli have been shown to inhibit the proliferation of several types of
      cancer cells, but the effects of vaginal Lactobacilli on cervical cancer cells
      have seldom been reported. We incubated Caski cells with supernatants of
      predominant strains in the vagina and investigated their effects on cell growth
      and the possible mechanisms. Cell-free supernatants of Lactobacillus crispatus,
      L. jensenii, and L. gasseri were prepared and purified. Caski cells were treated
      with various concentrations of Lactobacillus supernatants (LS). The effect of LS
      on cell growth was investigated using MTT assays. The influence of LS on the cell
      cycle and expression of human papillomavirus (HPV) E6 and E7 oncogenes was
      determined by flow cytometry and RT-PCR, respectively. LS-inhibited Caski cell
      proliferation caused morphological changes in a pH-independent manner. Flow
      cytometric analysis revealed that cells exposed to LS exhibited a significant
      increase of cell number in S phase and a strong decrease of cell number in G2/M
      phase. Expression of HPV E6 and E7 oncogenes, as well as CDK2 and cyclin A was
      decreased after treatment with LS, while expression of p21 was increased.
      Supernatants of L. crispatus, L. jensenii, and L. gasseri have inhibitory effects
      on the viability of cervical cancer cells via regulation of HPV oncogenes and
      cell cycle-related genes. Lactobacillus, as a promising treatment for cancer, is
      being assessed for its effect, and these results provide further evidence in this
      respect.

PMID- 29071556
TI  - The efficacy of probucol combined with hydration in preventing contrast-induced
      nephropathy in patients with coronary heart disease undergoing percutaneous
      coronary intervention: a multicenter, prospective, randomized controlled study.
AB  - PURPOSE: To investigate the preventive effect of probucol combined with hydration
      on contrast-induced nephropathy (CIN) in patients with coronary heart disease
      undergoing percutaneous coronary intervention (PCI). METHODS: A total of 641
      patients undergoing PCI were randomly assigned to either a probucol group
      (probucol 500 mg twice daily and hydration; n = 321) or a control group
      (hydration only; n = 320). The primary endpoint was the incidence of CIN, defined
      as an increase in serum creatinine (Scr) by >= 44.2 MUmol/L or >= 25% within 72 h
      after the administration of contrast agent. Secondary endpoints were changes in
      Scr, cystatin-C (Cys-C), creatinine clearance rate (Ccr), C-reactive protein
      (CRP), superoxide dismutase (SOD), and glutathione (GSH) within 72 h, and major
      adverse events during hospitalization or the 14-day follow-up period. RESULTS:
      The incidence of CIN was 4.0% (13/321) in the probucol group and 10.9% (35/320)
      in the control group. The probucol group had lower Cys-C and higher Ccr at 48 and
      72 h after PCI compared with the control group. At 48 and 72 h following the
      operation, Cys-C and CRP were lower in the probucol group compared with the
      control group, but Ccr, SOD, and GSH were higher. There were no differences in
      the incidence of major adverse events during hospitalization or the 14-day follow
      up between the groups. Multivariate logistic regression analysis showed that
      probucol was an independent protective factor for CIN. CONCLUSIONS: Probucol
      combined with hydration more effectively decreased the incidence of CIN in
      patients with coronary heart disease undergoing PCI compared with hydration
      alone.

PMID- 29071559
TI  - Successful retinal blood flow augmentation after extracranial-intracranial
      bypass.
AB  - A 61-year-old woman visited us with recent onset right-side weakness. Magnetic
      resonance imaging showed ischemic changes at the left internal border zone due to
      occlusive disease affecting the left proximal internal carotid artery. Prompt
      oral dual antiplatelet therapy and intravenous fluid were administered with
      subsequent induced hypertension and without reperfusion therapy. Although the
      hemiparesis was improved, she complained of a new-onset transient left-side
      monocular visual loss. Fluorescein angiography confirmed delayed perfusion in the
      left eye. We performed extracranial-intracranial bypass for flow augmentation.
      After bypass, the amaurosis fugax resolved. Follow-up retinal fluorescein
      angiography also showed improved retinal perfusion.

PMID- 29071558
TI  - The relation between brain MRI findings and blood manganese levels in renal
      transplantation, hemodialysis, and peritoneal dialysis patients.
AB  - PURPOSE: Various factors can affect blood and tissue levels of trace elements in
      patients with end-stage renal disease. There are a few studies showing
      hyperintensity of basal ganglia associated with manganese deposition in
      hemodialysis (HD) patients. The present study aimed to investigate the intensity
      changes as markers of manganese deposition in the basal ganglia and to
      demonstrate their association with blood manganese levels using ICP/MS technique
      in HD, peritoneal dialysis (PD), and renal transplant patients. METHODS: The
      study included 20 HD, 20 PD, 20 renal transplant patients, and 20 healthy
      controls. Blood manganese levels were obtained, and cranial magnetic resonance
      images were evaluated for basal ganglia hyperintensity. RESULTS: Blood manganese
      levels were similar across all study groups (p = 0.308), whereas symmetric basal
      ganglia hyperintensity indicating manganese deposition was detected only in HD
      patients (p = < 0.001). There was a significant relationship between manganese
      deposition and duration of dialysis (p = 0.05). CONCLUSION: Imaging findings
      suggesting manganese deposition in the basal ganglia being present only in HD
      patients suggest that manganese deposition could be caused by the hemodialysis
      method itself rather than uremia and renal failure. Further studies are required
      in this regard, as previous studies have not clearly identified the mechanisms by
      which hemodialysis causes these changes.

PMID- 29071557
TI  - Collectins in urinary tract and kidney diseases.
AB  - The innate immune system serves as the frontline defense against invading
      pathogens and initiates an inflammatory response to microorganisms. Collectins
      are C-type lectins that are structurally characterized by a collagen-like
      sequence and a carbohydrate recognition domain. Moreover, they are widely
      expressed throughout the body and are involved in the innate immunity against a
      variety of pathogens, regulating inflammation, and protecting the lungs from
      pathogens. Recently, two classical collectins, surfactant protein A (SP-A) and
      surfactant protein D (SP-D), as well as novel collectin 11, were found present in
      urinary tract tissues. They are increasingly recognized as key players in
      activating the humoral arm of innate immunity and host defense in urinary tract
      and kidney diseases, although their biological features, functions, and
      mechanisms in this regard remain largely unclear. In this review, we aim to
      integrate results reported by ourselves and others to summarize and gain a better
      understanding of the functions of collectins (SP-A, SP-D, and collectin 11) in
      urinary tract and kidney diseases.

PMID- 29071560
TI  - Sevoflurane Affects Oxidative Stress and Alters Apoptosis Status in Children and
      Cultured Neural Stem Cells.
AB  - Anesthesia-induced neurotoxicity in immature animals has raised concerns about
      similar effects occurring in young children. Our study investigated two commonly
      used anesthetics-sevoflurane and propofol-for neurotoxicity in young children.
      Forty-seven children (aged 12-36 months) undergoing hypospadias repair surgery
      were randomized to receive sevoflurane (SG, n = 24) or propofol (PG, n = 23)
      general anesthesia. Venous blood was collected at three different times
      immediately after induction, 2 h, and 3 days after surgery. The cellular portion
      was assessed for antioxidant defense and DNA damage, using enzyme assay kits and
      qRT-PCR, respectively, while serum was used to treat cultured neural stem cells
      (NSCs). MTT assay and TUNEL staining were performed, and the mRNA levels of
      antioxidant enzymes and apoptosis indicators were evaluated by qRT-PCR.
      Antioxidant defense and apoptosis status in the SG group were significantly
      higher than in the PG group at 2 h after surgery. Additionally, exposure of NSCs
      to postoperative serum of the SG group resulted in decreased cell density and
      viability, increased TUNEL-positive cells, elevated mRNA levels of antioxidant
      enzymes, and cleaved caspase-3 expression. Our data shows for the first time that
      in young children, administration of sevoflurane, but not propofol, leads to
      temporally increased antioxidant defense and apoptosis status as well as damage
      of NSCs.

PMID- 29071561
TI  - Color adjustment potential of resin composites.
AB  - OBJECTIVES: The purpose of this study was to evaluate color adjustment potential
      (CAP) of resin composites. MATERIALS AND METHODS: Two shades of each of eight
      commercial resin composites and one control shade were evaluated. Visual (color
      competent observers, controlled conditions) and instrumental color evaluations
      (spectroradiometer, spectrophotometer) were performed. The data were analyzed by
      analysis of variance, Fisher's PLSD intervals for comparison of means, and
      Spearman's rank order correlation. RESULTS: Instrumental color adjustment
      potential (CAP-I) ranged from - 0.51 to 0.74, and corresponding Fisher's PLSD
      intervals were 0.1 and 0.05, respectively (p < 0.0001, power 1.0). Visual color
      adjustment potential (CAP-V) ranged from 0.10 to 0.78, and corresponding Fisher's
      PLSD intervals were 0.2 and 0.1, respectively (p < 0.0001, power 1.0). The
      greatest overall color shifting between test shades in isolation and the same
      shades surrounded by control shade were recorded for HRi ENA enamel, followed by
      Clearfil Majesty ES2. The highest visual CAP (blending) was recorded for
      Herculite Ultra, HRi ENA enamel, and Clearfil Majesty ES2. CONCLUSION: Within the
      limitation of the study, it was found that color adjustment potential (CAP) was
      composite and shade-dependent. Positive CAP was recorded both instrumentally and
      visually for majority of composites and shades. Overall, the measured color
      difference reduction associated with positive CAP was 31%, while the average
      visual CAP was 43%. CLINICAL RELEVANCE: Resin composites with pronounced color
      adjustment potential interact with surrounding dental restorations. Introduced
      CAP-V and CAP-I were indirect measurements of blending (optical illusion).

PMID- 29071563
TI  - Collateral Effects of Youth Disruptive Behavior Disorders on Mothers'
      Psychological Distress: Adolescents with Autism Spectrum Disorder, Intellectual
      Disability, or Typical Development.
AB  - Disruptive behavior disorders were assessed in 160 youth aged 13 years, with
      Autism Spectrum Disorder (ASD, n = 48), intellectual disability (ID, n = 28), or
      typical development (TD, n = 84). Mothers' reported collateral effects on their
      psychological adjustment were related to both youth disability status and
      clinical level behavior disorders. More youth with ASD or ID had clinical level
      behavior disorders than their TD peers, and their mothers reported significantly
      higher personal stress and psychological symptoms, as well as lower positive
      impact of the youth on the family. The youth's clinical level behavior disorders
      accounted for these differences more than the diagnostic status. Mothers high in
      dispositional optimism reported the lowest stress and psychological symptoms in
      relationship to youth behavior challenges.

PMID- 29071562
TI  - The effect of light quality on the pro-/antioxidant balance, activity of
      photosystem II, and expression of light-dependent genes in Eutrema salsugineum
      callus cells.
AB  - The antioxidant balance, photochemical activity of photosystem II (PSII), and
      photosynthetic pigment content, as well as the expression of genes involved in
      the light signalling of callus lines of Eutrema salsugineum plants (earlier
      Thellungiella salsuginea) under different spectral light compositions were
      studied. Growth of callus in red light (RL, maximum 660 nm), in contrast to blue
      light (BL, maximum 450 nm), resulted in a lower H2O2 content and thiobarbituric
      acid reactive substances (TBARS). The BL increased the activities of key
      antioxidant enzymes in comparison with the white light (WL) and RL and
      demonstrated the minimum level of PSII photochemical activity. The activities of
      catalase (CAT) and peroxidase (POD) had the highest values in BL, which, along
      with the increased H2O2 and TBARS content, indicate a higher level of oxidative
      stress in the cells. The expression levels of the main chloroplast protein genes
      of PSII (PSBA and PSBD), the NADPH-dependent oxidase gene of the plasma membrane
      (RbohD), the protochlorophyllide oxidoreductase genes (POR B, C) involved in the
      biosynthesis of chlorophyll, and the key photoreceptor signalling genes (CIB1,
      CRY2, PhyB, PhyA, and PIF3) were determined. Possible mechanisms of light quality
      effects on the physiological parameters of callus cells are discussed.

PMID- 29071565
TI  - Assessing Personal Constructs of Adolescents with Autism Spectrum Disorder: A
      Person-Centered Measure of Social Cognition.
AB  - Many protocols assessing social communication skills of adolescents with autism
      spectrum disorder (ASD) are based on behavioral observations. It has been
      suggested, however, that social cognition encompasses processes underlying
      observable behaviors. Such processes include personal constructs, which can be
      assessed using repertory grids. Personal constructs of five adolescents with ASD
      with average or above average intelligence and receptive and expressive language
      skills were explored using repertory grids in this study. With visual structure
      and verbal scaffolding, all participants successfully engaged in the repertory
      grid process. Data suggest participants had well organized, complex construct
      systems, a significant understanding of social roles, and were interested in
      social interactions. Repertory grids may provide additional person-centered
      information for assessing social communication skills in ASD.

PMID- 29071564
TI  - An Ecosystem Approach to Employment and Autism Spectrum Disorder.
AB  - Relatively little is yet known about employment readiness and elements that
      promote access to, and the retention of, employment for adults with autism
      spectrum disorder (ASD). This paper posits elements within the ecosystem of
      employment and ASD. The ecosystem approach locates employment among persons with
      ASD as inextricably linked with broader community resources, family support,
      workplace capacity building (e.g., employer, co-workers) and policy. Application
      of the approach is offered through process evaluation data yielded from an
      ecosystem-informed job readiness program entitled, 'EmploymentWorks Canada'.
      Findings illustrate job readiness in the context of the broader ecosystem that
      envelopes salient components in the aim of community engagement and quality of
      life. Recommendations are offered for community-based applications and for
      program and research development.

PMID- 29071566
TI  - Experiences of Autism Acceptance and Mental Health in Autistic Adults.
AB  - Mental health difficulties are highly prevalent in individuals on the autism
      spectrum. The current study examined how experiences and perceptions of autism
      acceptance could impact on the mental health of autistic adults. 111 adults on
      the autism spectrum completed an online survey examining their experiences of
      autism acceptance, along with symptoms of depression, anxiety and stress.
      Regression analyses showed that autism acceptance from external sources and
      personal acceptance significantly predicted depression. Acceptance from others
      also significantly predicted stress but acceptance did not predict anxiety.
      Further analyses suggested that experiences of "camouflaging" could relate to
      higher rates of depression. The current study highlights the importance of
      considering how autism acceptance could contribute to mental health in autism.

PMID- 29071567
TI  - Novel anti-adipogenic activity of anti-malarial amodiaquine through suppression
      of PPARgamma activity.
AB  - Amodiaquine (AQ) was developed as a selective drug against Plasmodium falciparum
      malaria infection and has received increasing attention as a therapeutic agent
      for the treatment of rheumatoid arthritis, Parkinson's disease, and cancer due to
      its anti-inflammatory, anti-proliferative, and autophagic-lysosomal blockade
      properties. As autophagy activation is involved in promoting adipogenic
      differentiation, we examined whether anti-autophagic AQ affected adipocyte
      differentiation of 3T3-L1 pre-adipocytes. AQ dose-dependently and significantly
      suppressed adipocyte differentiation in conjunction with decreases in lipid
      droplet formation and expression of adipogenic markers including adiponectin,
      adipocyte fatty acid-binding protein 2 (aP2), resistin, and leptin. Although
      peroxisome proliferator-activated receptor gamma (PPARgamma) decreases by
      inhibition of autophagy, AQ treatment did not induce PPARgamma degradation
      despite the suppression of autophagolysosomal degradation. Instead, AQ suppressed
      the PPARgamma activity to transcriptionally activate the aP2 gene transcription
      through the selective prevention of nuclear localization of PPARgamma. These
      results demonstrated the novel anti-adipogenic activity of AQ and identified its
      underlying mechanism that AQ suppressed adipogenic gene expression and lipid
      formation by inhibiting nuclear localization of PPARgamma in an autophagy
      independent manner. AQ is recommended as a safe and effective anti-obesity drug
      for controlling overweight and obesity.

PMID- 29071568
TI  - Urban and Rural Adolescents' Points-of-Access for Alcohol and Tobacco.
AB  - The purpose of this study was to examine alcohol and tobacco access points among
      a sample of rural and urban youth. Through collaboration with four regional
      school districts, a local drug prevention coalition administered a survey to a
      sample of 445 youth representing 30 different communities in a central U.S.
      region. The survey items included demographics, 30-day use measures, and
      questions about points-of-access for alcohol and tobacco. Results showed no
      differences among points-of-access between urban and rural youth. Ability to
      obtain alcohol from family, peers, other non-peer youth, and other non-family
      adults (P < 0.05) were each statistically significant predictors of 30-day
      alcohol use. Ability to obtain tobacco from family, peers, other non-peer youth,
      other non-family adults, and self-purchase (P < 0.05) were statistically
      significant predictors of 30-day tobacco use. Access through peers was the
      strongest predictor for both 30-day alcohol and tobacco use. Determining the
      primary social points-of-access youth use to obtain alcohol and tobacco can
      assist in the development of appropriate community-level prevention strategies
      and policies.

PMID- 29071569
TI  - A Community-Based "Street Team" Tobacco Cessation Intervention by and for Youth
      and Young Adults.
AB  - Most tobacco users initiate use as youth or young adults. To promote tobacco
      cessation for this group and encourage non-users' engagement in tobacco control
      efforts, a community-based organization developed a "Street Team" brief outreach
      intervention that enlisted youth and young adults to encourage their peers to
      stop tobacco use through a brief intervention. Street Team members provided
      education, a Quit Kit, and referrals to cessation resources at a total of 27
      community events over a four-year period. Tobacco users (n = 279) completed
      assessments of tobacco use, quit intention, and quit self-efficacy at baseline.
      Self-reports of cessation outcomes including past week abstinence were assessed 1
      , 3-, and 6-months post-intervention. Perceptions of the intervention were
      gathered from Street Team members (n = 28) and intervention participants post
      intervention. T-tests and chi2-tests were used to compare those who completed at
      least one follow-up assessment to those lost to follow-up. Time effects were
      analyzed using fixed effect models. Missing = using analyses indicate 16.1, 18.6,
      and 12.5% 7-day quit rate at 1-, 3-, and 6-months follow-up. Feedback from
      intervention participants indicate the intervention was acceptable and that
      discussions with Street Team members and provision of quit kits motivated tobacco
      users to consider quitting. All Street Team members responded positively to their
      participation in the intervention. This Street Team approach for youth and young
      adults is promising as an effective approach to the promotion of tobacco
      cessation among users and engagement and empowerment in tobacco control efforts
      among non-users.

PMID- 29071570
TI  - P-Hacking: A Wake-Up Call for the Scientific Community.
AB  - P-hacking or data dredging involves manipulation of the research data in order to
      obtain a statistically significant result. The reasons behind P-hacking and the
      consequences of the same are discussed in the present manuscript.

PMID- 29071571
TI  - Perceptions of Ethical Climate and Research Pressures in Different Faculties of a
      University: Cross-Sectional Study at the University of Split, Croatia.
AB  - We determined the prevailing ethical climate at three different schools of a
      single university, in order to explore possible differences in the ethical
      climate related to different research fields: the School of Electrical
      Engineering, Mechanical Engineering, and Naval Architecture; the School of
      Humanities and Social Sciences; and the School of Medicine. We used the Ethical
      Climate Questionnaire to survey the staff (teachers and administration) at the
      three schools, and used the research integrity and organizational climate (RIOC)
      survey for early-stage researchers at the three schools. The dominant ethical
      climate type perceived collectively at the three university schools (response
      rate 49%, n = 294) was Laws and professional codes, which is associated with the
      cosmopolitan level of analysis and the ethical construct of principle.
      Individually, the same climate predominated at the schools for engineering and
      humanities, but the School of Medicine had the Self-interest ethical climate,
      which is associated with the individual level of analysis and the egoism ethical
      construct. In the RIOC survey (response rate 85%; n = 70), early-stage
      researchers from the three university schools did not differ in their perceptions
      of the organizational research integrity climate, or in their perceived
      individual, group or organizational pressures. Our study is the first, to the
      best of our knowledge, to show differences in perceived ethical climate at a
      medical school compared to other schools at a university. Further studies are
      needed to explore the reasons for these differences and how they translate to
      organizational outcomes, such as job satisfaction, commitment to the institution
      and dysfunctional behaviour, including research misconduct.

PMID- 29071572
TI  - Tri-parent Baby Technology and Preservation of Lineage: An Analysis from the
      Perspective of Maqasid al-Shari'ah Based Islamic Bioethics.
AB  - Tri-parent baby technology is an assisted reproductive treatment which aims to
      minimize or eliminate maternal inheritance of mutated mitochondrial DNA (mtDNA).
      The technology became popular following the move by the United Kingdom in
      granting license to a group of researchers from the Newcastle Fertility Centre,
      Newcastle University to conduct research on the symptoms of defective mtDNA. This
      technology differs from other assisted reproductive technology because it
      involves the use of gamete components retrieved from three different individuals.
      Indirectly, it affects the preservation of lineage which is important from an
      Islamic point of view. This paper aims to analyze and discuss the implications of
      the tri-parent technology on preservation of lineage from the perspective of
      Maqasid al-Shari'ah based the Islamic bioethics. The analysis shows that there
      are a few violations of the preservation of lineage, hence the tri-parent baby
      technology should not be permitted.

PMID- 29071573
TI  - A Systems Approach to Understanding and Improving Research Integrity.
AB  - Concern about the integrity of empirical research has arisen in recent years in
      the light of studies showing the vast majority of publications in academic
      journals report positive results, many of these results are false and cannot be
      replicated, and many positive results are the product of data dredging and the
      application of flexible data analysis practices coupled with selective reporting.
      While a number of potential solutions have been proposed, the effects of these
      are poorly understood and empirical evaluation of each would take many years. We
      propose that methods from the systems sciences be used to assess the effects,
      both positive and negative, of proposed solutions to the problem of declining
      research integrity such as study registration, Registered Reports, and open
      access to methods and data. In order to illustrate the potential application of
      systems science methods to the study of research integrity, we describe three
      broad types of models: one built on the characteristics of specific academic
      disciplines; one a diffusion of research norms model conceptualizing researchers
      as susceptible, "infected" and recovered; and one conceptualizing publications as
      a product produced by an industry comprised of academics who respond to
      incentives and disincentives.

PMID- 29071574
TI  - Professor Ju-Chi Li, one of the pioneers and founders of modern genetics in
      China.

PMID- 29071575
TI  - Time Until Partial Response in Metastatic Adrenocortical Carcinoma Long-Term
      Survivors.
AB  - A partial response (PR) has been proposed as a surrogate for overall survival in
      advanced adrenocortical carcinoma (ACC). The primary endpoint of the study was to
      characterize the time until a PR in patients with metastatic ACC treated with a
      standard therapy is achieved. Long-term survivors were selected to allow
      evaluation of delayed tumor response to mitotane. Records from patients with
      metastatic ACC that survived for > 24 months were retrieved. Tumor response was
      analyzed according to the Response Evaluation Criteria in Solid Tumors (RECIST)
      1.1 criteria. Time until a tumor response, after treatment initiation or
      therapeutic plasma mitotane level, was analyzed. Sixty-eight patients were
      analyzed. The first-line systemic therapy was mitotane as a monotherapy (M) (n =
      57) or cytotoxic polychemotherapy plus/minus mitotane (PC +/- M) (n = 11). The
      second-line therapy was M (n = 2) or PC +/- M (n = 41). Thirty-two PRs occurred
      in 30/68 patients (44.1%): this was obtained for 13 (40.6%) during M and during
      PC +/- M for 19/32 responders (59.4%). PRs were observed within 6 months of
      starting M or PC +/- M in 76.9 and 94.7% of responses, respectively, within 6
      months of therapeutic plasma mitotane being first observed in 88.9% of responses
      with M and in 53.3% of responses with PC +/- M. All PRs (but one) occurred within
      1 year after initiating treatment. To conclude, Most patients with metastatic ACC
      and long survival times had PRs within the first 6 months of standard systemic
      therapy, and almost all within the first year. The absence of response after that
      period could be considered as a treatment failure. Maintenance of mitotane
      therapy in non-responders after 1 year should be questioned in future randomized
      trials.

PMID- 29071576
TI  - NMR assignments of the N-terminal signaling domain of the TonB-dependent outer
      membrane transducer PupB.
AB  - Outer membrane TonB-dependent transducers (TBDTs) actively transport ferric
      siderophore complexes from the extracellular environment into Gram-negative
      bacteria. They also participate in a cell-surface signaling regulatory pathway
      that results in upregulation of the transducer itself, in response to iron
      deplete conditions. The TBDT PupB transports ferric pseudobactin, and signals
      through its N-terminal signaling domain (NTSD), while the TBDT homolog PupA is
      signaling-inactive. Here, we report the NMR chemical shift assignments of the
      PupB-NTSD. This information will provide the basis for structural
      characterization of the PupB-NTSD to further explore its signaling properties.

PMID- 29071577
TI  - Obstetric care quality indicators and outcomes based on the degree of
      acculturation of immigrants-results from a cross-sectional study in Berlin.
AB  - HYPOTHESIS: Acculturation is a complex, multidimensional process involving the
      integration of the traditional norms, values, and lifestyles of a new cultural
      environment. It is, however, unclear what impact the degree of acculturation has
      on obstetric outcomes. METHODS: Data collection was performed in 2011 and 2012 at
      three obstetric tertiary centers in Berlin, Germany. Standardized interviews (20
      30 min.) were performed with support of evaluated questionnaires. The primary
      collected data were then linked to the perinatal data recorded at the individual
      clinics provided from the obstetric centers which correspond with the routinely
      centralized data collected for quality assurance throughout Germany. The
      questionnaire included questions on sociodemographic, health care, and migrant
      related aspects. Migrant women and women with a migration background were
      assessed using the Frankfurt Acculturation Scale, a one-dimensional measurement
      tool to assess the degree of acculturation (15 items on language and media usage
      as well as integration into social networks). RESULTS: In summary, 7100 women
      were available for the survey (response rate of 89.6%) of which 3765 (53%) had a
      migration background. The probability of low acculturation is significantly (p <
      0.001) associated with a lower level of German knowledge, a shorter period of
      residence, and lower education. Pregnant women with a low acculturation also had
      a significantly greater chance of having the first booking visit after 9 weeks of
      pregnancy and fewer ultrasound examinations during pregnancy. There is no
      significant difference depending on the degree of acculturation for the frequency
      of elective and emergency cesarean sections. The results of the logistic
      regression analyses for the examination of possible relationships between the
      degree of acculturation and obstetric parameters show no significant differences
      for prematurity, 5 min.-Apgar values > 7, arterial umbilical cord pH values >
      7.00 and admissions to the neonatal unit. CONCLUSIONS: In Berlin, among migrant
      women a low degree of acculturation may have an unfavorable effect on the
      utilization of pregnancy care provision. However, there were no relevant
      differences in obstetric outcome parameters in relation to the degree of
      acculturation within the migrant population of Berlin.

PMID- 29071578
TI  - Expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells, follicular
      fluid, and serum of women with polycystic ovary syndrome (PCOS).
AB  - PURPOSE: Polycystic ovary syndrome (PCOS) is one of the most common
      endocrinopathies that affects women in reproductive age. MicroRNAs (miRNAs) play
      crucial roles in normal function of female reproductive system and
      folliculogenesis. Deregulated expression of miRNAs in PCOS condition may be
      significantly implicated in the pathogenesis of PCOS. We determined relative
      expression of miR-15a, miR-145, and miR-182 in granulosa-lutein cells (GLCs),
      follicular fluid (FF), and serum of PCOS patients. METHODS: Human subjects were
      divided into PCOS (n = 20) and control (n = 21) groups. GLCs, FF, and serum were
      isolated and stored. RNA isolation was performed and cDNA was reversely
      transcribed using specific stem-loop RT primers. Relative expression of miRNAs
      was calculated after normalization against U6 expression. Correlation of miRNAs'
      expression level with basic clinical features and predictive value of miRNAs in
      FF and serum were appraised. RESULTS: Relative expression of miR-145 and miR-182
      in GLCs was significantly decreased in PCOS, but miR-182 in FF of PCOS patients
      revealed up-regulated levels. Significant correlations between level of miRNAs in
      FF and serum and hormonal profile of subjects were observed. MiR-182 in FF showed
      a significant predictive value with AUC of 0.73, 76.4% sensitivity, and 70.5%
      specificity which was improved after combination of miR-182 and miR-145.
      CONCLUSIONS: A significant dysregulation of miR-145 and miR-182 in GLCs of PCOS
      may indicate their involvement in pathogenesis of PCOS. Differential up
      regulation of miR-182 in FF of PCOS patients with its promising predictive values
      for discrimination of PCOS reinforced the importance of studying miRNAs' profile
      in FF.

PMID- 29071579
TI  - Passive smoking, NAT2 polymorphism, and breast cancer risk in Israeli Arab women:
      a case-control study.
AB  - BACKGROUND: The effect of passive smoking (PS) on breast cancer (BC) is
      controversial, and may be modified by polymorphism of the N-Acetyl-transferase
      (NAT) 2 enzyme which is involved in tobacco carcinogen metabolism. We aimed to
      evaluate the relationship between PS and BC by NAT2 variants in Arab-Israeli
      women, a unique population with low active smoking rates, and high exposure to
      PS. METHODS: A population-based case-control study was carried out on non-smoking
      137 prevalent breast cancer patients and 274 population-based controls, aged 30
      70 years. Data on past and current PS, sociodemographic, and other
      characteristics were retrieved through interviews, and buccal smears were
      provided for NAT2 analyses. Logistic regression models adjusting for potential
      confounders assessed the odds ratios (ORs) and 95% confidence intervals (95% CI)
      of the association between PS and BC. RESULTS: Ever PS was associated with
      increased BC risk: OR = 2.22, 95% CI 1.28-3.87. Higher lifetime PS exposure was
      associated with higher BC risk: Compared to never exposed women, women exposed to
      PS most of their lives had a threefold higher BC risk (OR = 3.16, 95% CI 1.70
      5.87, P trend < 0.001). NAT2 polymorphism did not modify these associations.
      CONCLUSIONS: PS exposure in non-smoking Israeli Arab women is significantly
      associated with increased risk for BC, potentially allowing for specific
      intervention; NAT2 polymorphism does not modify this association.

PMID- 29071580
TI  - Congenital Vertebral Arteriovenous Fistula.

PMID- 29071581
TI  - Microangiopathic Hemolytic Anemia - A Rare Presentation of Vitamin B12
      Deficiency.

PMID- 29071582
TI  - Medical Treatment of Hematuria Due to Bladder Hemangioma in a Newborn.

PMID- 29071583
TI  - Bilateral Ptosis: A Rare Presentation of Hydrocephalus.

PMID- 29071584
TI  - Childhood Brucellosis in Eastern India.
AB  - OBJECTIVE: To investigate the presence of childhood brucellosis presenting as PUO
      (pyrexia of unknown origin) cases in Eastern zone of India. METHODS: Blood
      samples were collected from PUO patients aged <=18 y. The main diagnostic tools
      were STAT, RBPT, ELISA- IgM, IgG and PCR. Although mainly PUO cases were selected
      for the study, other associated clinical manifestations were also noted. RESULTS:
      The findings revealed significantly higher percentage of infection in female
      children (14.3%) than in male children (10.9%). The positive results by different
      diagnostic tools, STAT, RBPT, ELISA- IgM, ELISA-IgG and brucella genus specific
      PCR were 10.6%, 7.2%, 7.2%, 0.85% and 1.3% respectively. Main associated clinical
      symptoms were joint pain, low backache, fatigue and night sweat. CONCLUSIONS:
      This hospital based study reflects a significant number of childhood brucellosis
      cases in Eastern zone of India, and thus emphasizes the need for further
      monitoring of such subjects.

PMID- 29071587
TI  - Pancreatic Metastases of Rectal Cancer-Case Report and Literature Review.

PMID- 29071585
TI  - Expanding the Phenotype of the Founder South Asian Mutation in the Nuclear
      Encoding Mitochondrial RMND1 Gene.
AB  - BACKGROUND: Mitochondrial disorders have a wide variability in the phenotype. A
      10-mo-old girl presented with a severe phenotype of multisystem involvement due
      to an uncommon mitochondrial disease. Mutations in the RMND1 gene of nuclear DNA
      were identified on next generation sequencing. This mutation results in combined
      oxidative phosphorylation deficiency -11 (OMIM #614922) of the respiratory chain
      complex. So far in South Asia, patients of this disorder have been reported only
      from Pakistan and Bangladesh. RESULTS: In addition to the features reported in
      other patients of South Asia with the same mutation at c.1349G>C, index patient
      from India had hyperaldosteronism, long QT interval but no deafness. CONCLUSIONS:
      Thus, to conclude, this report emphasizes the diagnostic value of FGF21 assay in
      this disorder. It extends the phenotype associated with the founder mutation in
      RMND1 gene in patients from South Asia.

PMID- 29071586
TI  - Maternal Vitamin D Status and Neonatal Outcomes.

PMID- 29071588
TI  - A Retrospective Medical Record Review of Utilization Patterns and Medical
      Resource Use Associated with Repository Corticotropin Injection among Patients
      with Rheumatologic Diseases in the United States.
AB  - INTRODUCTION: Repository corticotropin injection (RCI) has anti-inflammatory and
      immune-modulatory effects and is approved for multiple indications, including
      several rheumatologic conditions. The aims of this nationally representative,
      retrospective, observational study were to describe patient characteristics, RCI
      treatment patterns, and barriers to RCI use in patients with rheumatologic
      disease, and to compare medical resource use (MRU) before and after RCI therapy.
      METHODS: A random sample of US physicians was recruited to abstract the medical
      records of deidentified patients with a diagnosis of rheumatoid arthritis (RA),
      psoriatic arthritis (PsA), dermatomyositis/polymyositis (DM/PM), or systemic
      lupus erythematosus (SLE) who had been treated with RCI in the previous 24
      months. Patient characteristics and patterns of RCI use were identified. Mean MRU
      in the 3 months before and after RCI therapy was compared using paired-samples t
      tests. RESULTS: A total of 449 physicians abstracted the medical records of 217
      RA, 190 PsA, 254 DM/PM, and 95 SLE patients. In all groups combined, patients had
      received a mean of 3.3 treatment medications before initiating RCI. Most patients
      (75%-94%) were receiving RCI for the first time, indicating that repeated courses
      of RCI were uncommon. RCI was used as bridge therapy in 18% of patients.
      Approximately 24% of patients encountered an obstacle in accessing RCI, primarily
      insurance-related. After RCI therapy, the number of hospitalizations and hospital
      days were significantly reduced for all cohorts (all P < 0.05), and the number of
      outpatient visits was significantly lower for all cohorts (P < 0.05) except the
      SLE cohort (P = 0.3230). Study limitations include potentially incomplete data in
      the medical records and a relatively short duration for capturing MRU changes.
      CONCLUSIONS: RCI was used primarily as late-line therapy in patients with
      rheumatologic diseases. Medical resource use was significantly lower in the 3
      months after therapy compared with 3 months prior. This finding suggests that RCI
      may improve disease control and warrants further evaluation. FUNDING:
      Mallinckrodt Pharmaceuticals.

PMID- 29071591
TI  - App Review: Management Guide for Incidental Findings on CT and MRI.

PMID- 29071590
TI  - Racial/Ethnic Disparities in Morbidity and Mortality for Preterm Neonates
      Admitted to a Tertiary Neonatal Intensive Care Unit.
AB  - OBJECTIVE: The objective of this study was to assess whether in-hospital
      morbidity or mortality differed by race/ethnicity for preterm neonates admitted
      to the neonatal intensive care unit (NICU). STUDY DESIGN: In a retrospective
      cohort study, preterm infants, < 37 weeks, were admitted to the NICU from 1994 to
      2009. Exclusions included structural anomalies and aneuploidy. Primary outcome
      was in-hospital mortality (IHM). Secondary outcomes were respiratory distress
      syndrome (RDS), interventricular hemorrhage (IVH), necrotizing enterocolitis
      (NEC), and retinopathy of prematurity (ROP). Sub-analysis of very preterm (VPT)
      infants, < 28 weeks, was performed. Five racial/ethnic groups (REGs) were
      compared: White, Black, Hispanic, Asian, and Mixed. Associations were modeled by
      logistic regression. White neonates (WNs) were the referent group. Unadjusted and
      adjusted odds ratios and 95% confidence intervals for remaining REGs were
      reported. p value was significant at 5% for overall tests and at Bonferroni
      corrected level < 0.0125 for between-race comparisons with WNs. RESULTS: Four
      thousand nine hundred fifty-five preterm neonates were identified; 153 were
      excluded leaving 4802 for analysis. After controlling covariates that were chosen
      a priori, there was no difference across REGs for IHM (all between-race
      comparison p values > 0.0125). There was a significant difference in RDS among
      Black neonates (BNs) (aOR 0.57, 95% CI 0.45-0.73; p < 0.001) and Hispanic
      neonates (HNs) (aOR 0.67, 95% CI 0.50-0.89; p = 0.005) compared to WNs. The risk
      of ROP was significantly different across REGs with HNs having a 70% increase in
      ROP (aOR 1.70, 95% CI 1.15-2.49; p = 0.008) and Mixed neonates (MNs) experiencing
      a 55% reduction (aOR 0.45, 95% CI 0.29-0.68; p < 0.001) compared to WNs. There
      was no difference in IVH or NEC across REGs (all p values > 0.0125). In the VPT
      cohort sub-analysis, BNs experienced a significant 59% reduction in IHM compared
      to WNs (BNs aOR 0.41, 95% CI 0.22-0.73; p = 0.003). MNs experienced a 46%
      reduction in ROP compared to WNs (aOR 0.54, 95% CI 0.35-0.81; p = 0.004). There
      was no difference in RDS, IVH, or NEC in very preterm infants across REGs (all
      between comparison p values > 0.0125). CONCLUSION: In preterm neonates, in
      hospital mortality does not significantly differ across racial and ethnic groups.
      However, in very preterm infants, in-hospital mortality for Black neonates is
      improved. There are morbidity differences (RDS, ROP) seen among racial/ethnic
      groups.

PMID- 29071589
TI  - Melatonin increases human cervical cancer HeLa cells apoptosis induced by
      cisplatin via inhibition of JNK/Parkin/mitophagy axis.
AB  - Considering that chemotherapy resistance is vital to the progression of cervical
      carcinoma, emerging researchers are focused on developing anti-tumor drugs to
      assist the treatment efficiency of chemotherapy. Melatonin has anti-tumor
      activity via several mechanisms including its anti-proliferative and pro
      apoptotic effects as well as its potent pro-oxidant action in tumor cells.
      Therefore, melatonin may be useful for the treatment of tumors in association
      with chemotherapy drugs. Here, we studied the effect and mechanism of melatonin
      on HeLa cells apoptosis under cisplatin (CIS) treatment, particularly focusing on
      the caspase-9-related apoptosis pathway and mitophagy-mediated anti-apoptotic
      mechanism. The result indicated that co-stimulation of HeLa cells with CIS in the
      presence of melatonin further increased cellular apoptosis. Furthermore,
      concomitant treatments with melatonin and CIS significantly enhanced the
      mitochondrial structure and function damage, substantially augmented the caspase
      9-dependent mitochondrial apoptosis with evidenced by lower mitochondria membrane
      potential, higher mitochondria ROS, and more pro-apoptotic proteins compared to
      the treatment with CIS alone. Mechanistically, melatonin inactivated mitophagy
      via blockade of JNK/Parkin, leading to the inhibition of anti-apoptotic
      mitophagy. The mitophagy had the ability to clear and remove damaged
      mitochondria, impairing CIS-mediated mitochondrial apoptosis. Activation of
      JNK/Parkin could alleviate the lethal effect of melatonin on HeLa cells. In
      summary, this study confirmed that melatonin sensitizes human cervical cancer
      HeLa cells to CIS-induced apoptosis through inhibition of JNK/Parkin/mitophagy
      pathways.

PMID- 29071593
TI  - [Diagnosis and therapy of tinnitus].

PMID- 29071592
TI  - Detection and Segmentation of Pectoral Muscle on MLO-View Mammogram Using
      Enhancement Filter.
AB  - The presence of predominant density region of the pectoral muscle in Medio
      Lateral Oblique (MLO) view of the mammograms can affect or bias the results of
      mammograms processing for breast cancer detection using intensity based methods.
      Therefore, to improve the diagnostic performance of breast cancer detection using
      computer-aided system, identification and segmentation of pectoral muscle is an
      important task. This paper presents, an intensity based approach to identify the
      pectoral region in mammograms. In the presented approach enhancement mask and
      threshold technique is used to enhance and select the pectoral region and
      boundary points respectively, to find the boundary of pectoral muscle. Then curve
      fitting by Least Square Error (LSE) method is used to refine the rough initial
      boundaries. The proposed approach was applied on 320 mammograms from mini
      Mammographic Image Analysis Society (mini-MIAS) database of 322 mammograms, with
      acceptable rate of 96.56% from radiologist experts. The performance evaluation
      for pectoral muscle segmentation, based on Hausdorff distance (H d ), False
      Positive (FP) and False Negative (FN) rate, shows the usefulness and
      effectiveness of the proposed approach.

PMID- 29071594
TI  - ?

PMID- 29071595
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PMID- 29071596
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PMID- 29071597
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PMID- 29071598
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PMID- 29071599
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PMID- 29071600
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PMID- 29071601
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PMID- 29071602
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PMID- 29071603
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PMID- 29071610
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PMID- 29071611
TI  - ?

PMID- 29071612
TI  - [Initial management of a suspected retroperitoneal soft tissue tumor - biopsy vs.
      primary resection].

PMID- 29071613
TI  - [When should patients be referred to the pneumologist?]

PMID- 29071615
TI  - [Hypertension and diabetes - dangerous syntropy].

PMID- 29071614
TI  - [Persistent cough in children].

PMID- 29071617
TI  - ?

PMID- 29071616
TI  - [Hypertension and renal disease].

PMID- 29071618
TI  - ?

PMID- 29071619
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PMID- 29071620
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PMID- 29071628
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PMID- 29071650
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PMID- 29071652
TI  - Detecting treatment-subgroup interactions in clustered data with generalized
      linear mixed-effects model trees.
AB  - Identification of subgroups of patients for whom treatment A is more effective
      than treatment B, and vice versa, is of key importance to the development of
      personalized medicine. Tree-based algorithms are helpful tools for the detection
      of such interactions, but none of the available algorithms allow for taking into
      account clustered or nested dataset structures, which are particularly common in
      psychological research. Therefore, we propose the generalized linear mixed
      effects model tree (GLMM tree) algorithm, which allows for the detection of
      treatment-subgroup interactions, while accounting for the clustered structure of
      a dataset. The algorithm uses model-based recursive partitioning to detect
      treatment-subgroup interactions, and a GLMM to estimate the random-effects
      parameters. In a simulation study, GLMM trees show higher accuracy in recovering
      treatment-subgroup interactions, higher predictive accuracy, and lower type II
      error rates than linear-model-based recursive partitioning and mixed-effects
      regression trees. Also, GLMM trees show somewhat higher predictive accuracy than
      linear mixed-effects models with pre-specified interaction effects, on average.
      We illustrate the application of GLMM trees on an individual patient-level data
      meta-analysis on treatments for depression. We conclude that GLMM trees are a
      promising exploratory tool for the detection of treatment-subgroup interactions
      in clustered datasets.

PMID- 29071653
TI  - Demographic, clinical, dispositional, and social-environmental characteristics
      associated with psychological response to a false positive ovarian cancer
      screening test: a longitudinal study.
AB  - Cancer screening can facilitate early detection that improves survival, but also
      can identify an abnormal finding that is not malignant and deemed benign. While
      such false positive (FP) results can impact a variety of psychological outcomes,
      little is known about demographic, clinical, dispositional, and social
      environmental characteristics associated with psychological outcomes after a FP
      result. Women participating in an ovarian cancer (OC) screening program and
      experiencing a FP screening test result (n = 375) completed assessments at
      baseline and 4-months. Results indicated greater social constraint and less
      education were linked to greater OC-specific distress at both assessments. Short
      term predictors included less optimism and no previous abnormal test, while
      longer-term predictors were fewer previous screens and the interaction between OC
      family history and monitoring coping style. Younger age, less education, less
      optimism, greater social constraint, and family history of OC were associated
      with greater perceptions of OC risk. Brief interventions prior to screening may
      minimize the negative impact of a false positive result and not interfere with
      compliant participation in screening programs.

PMID- 29071655
TI  - Editor's Comments.

PMID- 29071654
TI  - Measuring the "transfer of meaning" through members of equivalence classes merged
      via a class-specific reinforcement procedure.
AB  - Seven participants received conditional discrimination training that established
      the 12 conditional relations A1B1, A2B2, A3B3, A1C1, A2C2, A3C3, D1E1, D2E2,
      D3E3, D1F1, D2F2, and D3F3. The A stimuli were pictures of faces portraying
      emotional expressions; the others were arbitrary forms. Correct responses
      resulted in presentations of class-specific reinforcers, Sr1, Sr2, and Sr3. After
      training, tests confirmed the formation of ABC and DEF equivalence classes.
      Further tests then documented the merger of the classes and the emergence of SrB,
      SrC, SrE, and SrF relations, showing that the class-specific reinforcers were
      equivalence class members. Finally, participants did Semantic Differential
      ratings that tested whether the emotional valence of the A stimuli transferred to
      the arbitrary forms, B and E. The results show that participants' evaluations of
      the B and E stimuli were similar to evaluations of the A stimuli made by
      participants of a control group. This finding is considered as a demonstration
      that class-specific outcomes can mediate class merger phenomena and the transfer
      of functions through members of merged classes.

PMID- 29071656
TI  - Characterization of the Dissolution Behavior of Piperine/Cyclodextrins Inclusion
      Complexes.
AB  - In this study, the physicochemical properties and solubility of inclusion
      complexes of ground mixtures (GMs) of piperine (PP), a pungent ingredient of
      pepper, with alpha- and gamma-cyclodextrin (CD) were studied. From the solubility
      results, the PP/alphaCD inclusion molar ratio was determined to be 1/2, while
      that of PP/gammaCD was 1/1, according to the AP-type phase diagram of PP/alphaCD
      and the BS-type one of PP/gammaCD. The powder X-ray diffraction and differential
      scanning calorimetry analyses confirmed the formation of GM complexes with molar
      ratios of PP/alphaCD = 1/2 and PP/gammaCD = 1/1. The Raman analysis revealed the
      disappearance of the bands corresponding to the C=C, O-CH2-O, -CH, and aliphatic
      C=C moieties of the methylene dioxyphenyl fragment of PP in the spectra of the
      inclusion complexes. In the dissolution tests, GM (PP/alphaCD = 1/2) and GM
      (PP/gammaCD = 1/1) showed higher solubility than free PP and the analogous
      physical mixtures. Furthermore, after 60 min, GM (PP/alphaCD = 1/2) exhibited
      higher solubility than GM (PP/gammaCD = 1/1). In the 1H-1H nuclear Overhauser
      effect spectroscopy measurements, GM (PP/alphaCD = 1/2) was found to present a
      head-to-head inclusion structure via the aliphatic C=C and methylene dioxyphenyl
      groups of PP and the two alphaCD molecules. In contrast, it was confirmed that
      gammaCD interacts with the O-CH2-O functionality of the methylene dioxyphenyl
      group of PP in a molar ratio of 1/1. It was thus concluded that the differences
      in the PP/CD structures influence the solubility of the inclusion complexes.

PMID- 29071657
TI  - The Changing Face of Surgical Oncology.

PMID- 29071658
TI  - Vitamin D Levels Affect Breast Cancer Survival Rates: A Reply.

PMID- 29071659
TI  - Reply to: Partial Verification Distorts Estimates of Sensitivity in Diagnostic
      Accuracy Studies for Fine-Needle Aspiration Cytology.

PMID- 29071661
TI  - The Role of Intersphincteric Resection in Very Low Rectal Cancer.

PMID- 29071663
TI  - Usefulness of lung ultrasound in the management of patients with heart failure.

PMID- 29071662
TI  - Hemoglobin concentration is associated with self-reported disability and reduced
      physical performance in a community dwelling population of nonagenarians: the
      Mugello Study.
AB  - People aged 90 and older represent a fast-growing population segment who deserve
      specific attention and research. Aging is associated with a progressive decrease
      in hemoglobin concentration, which predicts adverse outcome, such as mortality,
      morbidity, frailty and disability. Whether this association is independent from
      increased prevalence of comorbidity, causing both anemia and reduced physical
      function is yet under debate. The aim of this study is to explore the
      relationship between hemoglobin concentration and self-reported disability and
      reduced physical performance in a community dwelling population of nonagenarians.
      Data presented were collected in the framework of the Mugello Study, a clinical
      epidemiologic survey of nonagenarians living in the Mugello area (Tuscany,
      Italy). 251 persons (177 women, age 93.2 +/- 3.3 years; 74 men, age 92.2 +/- 2.5
      years) underwent a blood draw. Along with hemoglobin concentration, self-reported
      disability (basic and instrumental activities of daily living), physical
      performance (Short Physical Performance Battery), self-reported physical activity
      and muscular strength (handgrip measurement) were assessed. Covariates, inherent
      sociodemographic and health indicators and comorbidities were also included in
      the analysis. This study confirms that anemia is very common in the oldest old,
      with a significantly higher prevalence in males (50% in men vs 24% in women).
      Multiple linear regression analysis, including all the comorbid conditions as
      confounding factors, shows that hemoglobin concentration is independently
      associated with handgrip strength, self-reported physical activity and disability
      in dressing, and taking a shower/bath. In conclusion, results from this study
      confirm that in the oldest old, low hemoglobin concentration is strongly
      associated with self-reported disability and decline of physical performance
      independent of comorbidity.

PMID- 29071660
TI  - Impact of RAS Mutations in Metastatic Colorectal Cancer After Potentially
      Curative Resection: Does Site of Metastases Matter?
AB  - BACKGROUND: RAS mutation status is an important prognostic factor after resection
      of liver metastases (LiM) from colorectal cancer (CRC). The prognostic
      significance of RAS after resection of lung (LuM) and peritoneal (PM) metastases
      from CRC is unknown. METHODS: Between 2005 and 2014, all consecutive patients
      with known RAS status who underwent potentially curative resection for LiM, LuM,
      or PM were evaluated. RESULTS: A total of 720 patients with known RAS status
      underwent resection of LiM (n = 468), LuM (n = 102), and PM (n = 150). RAS
      mutations were identified in 63 and 58% of patients with LuM and PM,
      respectively, compared with 41% of patients with LiM (p < 0.001). Five-year
      overall survival (OS) after resection of PM was 45%, compared with 52% after
      resection of LiM (p = 0.018) and 64% after resection of LuM (p = 0.005). RAS
      mutations were associated with significantly worse OS after resection of LiM (p <
      0.001), but did not affect OS among patients undergoing resection of LuM (p =
      0.41) and PM (p = 0.65). CONCLUSIONS: RAS mutations are more prevalent among
      patients undergoing resection of LuM and PM than LiM but do not affect survival
      after lung and peritoneal metastasectomy, as they do after hepatectomy. These
      results suggest that the prognostic significance of RAS mutations after resection
      of metastatic CRC depends on the specific site of metastases.

PMID- 29071664
TI  - The relationship between plasma interleukin-15 levels and sarcopenia in
      outpatient older people.
AB  - BACKGROUND AND AIM: Sarcopenia is a geriatric syndrome in which there is a
      decrease in muscle mass, muscle strength, and muscle function. Interleukin-15 (IL
      15), a myokine released by skeletal muscle, has effects on both muscle and
      adipose tissue. We evaluated the relationship between plasma IL-15 level and
      sarcopenia. METHODS: We evaluated a total of 160 outpatient older people, and 80
      of whom had sarcopenia. Sarcopenia was defined according to the European Working
      Group on Sarcopenia in Older People criteria. Plasma IL-15 was measured by enzyme
      linked immunosorbent assay. Activities of daily living, nutritional and exercise
      status, co-morbidities, body mass index, waist circumference, sensitive C
      reactive protein, IL-6, and vitamin D levels were also evaluated. RESULTS: IL-15
      levels were significantly higher in control subjects [5.1 (2.75-18.69)] compared
      to sarcopenic participants [3.91 (2.07-15.56)] (p < 0.001). Plasma IL-15 levels
      were independently and inversely associated with sarcopenia in multivariate
      regression analysis [OR: 0.74 (CI 95% 0.6-0.91) p = 0.005]. Age [OR: 1.13 (CI 95%
      1.01-1.27) p = 0.03] and BMI [OR: 0.68 (CI 95% 0.51-0.92)] were also associated
      with sarcopenia in multivariate regression analysis. CONCLUSIONS AND DISCUSSION:
      A low level of plasma IL-15 is associated with sarcopenia in outpatient older
      people. Further longitudinal and prospective studies are needed to evaluate
      changes in IL-15 over time together with muscle mass and strength or therapeutic
      potential of IL-15.

PMID- 29071666
TI  - Correction to: Expanding Antimicrobial Stewardship to Urgent Care Centers Through
      a Pharmacist-Led Culture Follow-up Program.
AB  - In the original publication, the data labels have been inverted in Figure 1. The
      corrected figure is given here.

PMID- 29071667
TI  - Association Between Maternal and Child Health Handbook and Quality of Antenatal
      Care Services in Palestine.
AB  - Objectives The Maternal and Child Health (MCH) handbook is an integrated home
      based record allowing clients to keep records on the continuum of care for
      mothers and children. This study aimed to assess associations between MCH
      handbook ownership and receipt of selected content of antenatal care services in
      Palestine. Methods Distribution of the MCH handbook in Palestine was launched in
      2008. We used an anonymous data set of the Palestinian Family Survey 2010 and
      analyzed the data of 2026 women who had live births within the past 12 months.
      Descriptive statistical analysis was conducted to assess differences between MCH
      handbook holders and non-holders. Multivariable logistic regression models were
      used to estimate adjusted odds ratios of the effects of MCH handbook use
      according to proxy indicators of antenatal care quality. Results Accounting for
      about 60% (n = 1202) of study participants, handbook holders were more likely to
      be primipara, live in the Gaza Strip, live in refugee camps, and live within a 30
      min distance to antenatal care facilities; however, household wealth levels for
      handbook holders were lower compared with non-holders. Handbook users had
      significantly higher odds of receiving all three kinds of medical tests and
      receiving information on five or more health education topics as part of
      antenatal care. The higher odds remained after adjusting for possible confounding
      variables, such as household wealth, region, residential area, birth order of the
      child, frequency of antenatal care, and time required to reach antenatal care
      facilities. Conclusions for Practice Use of the handbook as a portable checklist
      possibly promoted providers' higher adherence to the national guideline.

PMID- 29071665
TI  - New Viral and Immunological Targets for Hepatitis B Treatment and Cure: A Review.
AB  - Although current therapies can be successful at suppressing hepatitis B viral
      load, long-term viral cure is not within reach. Subsequent strategies combining
      pegylated interferon alfa with nucleoside/nucleotide analogues have not resulted
      in any major paradigm shift. An improved understanding of the hepatitis B virus
      (HBV) lifec ycle and virus-induced immune dysregulation has, however, revealed
      many potential therapeutic targets, and there are hopes that treatment of
      hepatitis B could soon be revolutionized. This review summarizes the current
      developments in HBV therapeutics-both virus directed and host directed.

PMID- 29071669
TI  - Automatic evaluation of myocardial perfusion on SPECT: Need for "Normality".

PMID- 29071668
TI  - Long-term study (2005-2010) on the vaccination with BoHV-1 glycoprotein E-deleted
      marker vaccine in selected two dairy herds in Turkey.
AB  - A follow-up study from 2005 to 2010 was carried out in two herds where
      eradication programme for the bovine herpes virus-1 (BoHV-1) infection depends on
      the vaccination with inactivated glycoprotein E-deleted vaccine that was started
      in 2001 following the vaccination with inactivated conventional vaccine between
      1999 and 2001. For serological screening, a total of 12,976 sera sampled over
      several sampling times approximately 6 months of interval during 5 years (2005
      2010) were tested for glycoprotein E (gE)- and glycoprotein B-specific antibodies
      using ELISA. According to the serological evidence, the long-term persistence of
      BoHV-1 antibodies, success of marker vaccine, first vaccination time of the
      calves in herds regularly vaccinated, etc. were discussed in this paper. In
      conclusion, the vaccination programme using gE (-) marker vaccines, with making
      efforts to prevent the other factors about transmission of infection, was
      suggested for the eradication of BoHV-1 infection in Turkey as many EU countries.
      This is the first report on the BoHV-1 eradication programme in some dairy cattle
      in Turkey.

PMID- 29071670
TI  - Added prognostic value of left ventricular shape by gated SPECT imaging in
      patients with suspected coronary artery disease and normal myocardial perfusion.
AB  - BACKGROUND: Left ventricular (LV) remodeling is associated with adverse
      cardiovascular events. We evaluated the added prognostic value of LV shape index
      (SI) assessed by gated single-photon emission tomography (SPECT) in patients
      without known coronary artery disease (CAD). METHODS AND RESULTS: We studied 674
      patients with normal myocardial perfusion and normal LV ejection fraction (EF) on
      stress gated SPECT imaging. An automated software program was used to calculate
      end-diastolic and end-systolic LVSI. An LVSI <= 0.54 at end-systole was
      considered normal. Follow-up was 96% complete with a median follow-up of 37
      months. During follow-up, 25 events occurred (3.8% cumulative event rate). Event
      free survival was lower in patients with abnormal end-systolic LVSI (P < .001).
      Age (P = .021), diabetes (P = .048), and end-systolic LVSI (P < .001) were
      independent predictors of events. LVSI added prognostic information increasing
      the global chi-square of the model including age and diabetes from 15.15 to 25.97
      (P < .001). The effect of diabetes on hazard ratio increased with increasing
      values of end-systolic LVSI. The probability of events at 48 months predicted by
      Weibull analysis progressively increased with increasing values of end-systolic
      LVSI and was higher in patients with diabetes as compared to those without.
      Decision curve analyses indicate that the model including end-systolic LVSI
      resulted in an increased net benefit between 5% and 30% threshold probability,
      indicating superior estimation of outcomes at low threshold probability levels.
      CONCLUSIONS: The evaluation of LVSI may identify patients with early-stage LV
      remodeling and at higher risk of adverse cardiac events, even in the presence of
      normal myocardial perfusion.

PMID- 29071671
TI  - SPECT quantification of myocardial blood flow: A journey of a thousand miles
      begins with a single step (Lao Tzu, Chinese philosopher, 604-531 BC).

PMID- 29071672
TI  - Flow Cytometry: The Glass Is Half Full.
AB  - Accompanied by a historical perspective of the field of cytometry, this
      introductory chapter provides a broad view of what flow cytometry can do; hence,
      the glass is half full.

PMID- 29071673
TI  - High-Dimensional Modeling for Cytometry: Building Rock Solid Models Using
      GemStoneTM and Verity Cen-se'TM High-Definition t-SNE Mapping.
AB  - This chapter outlines how to approach the complex tasks associated with designing
      models for high-dimensional cytometry data. Unlike gating approaches, modeling
      lends itself to automation and accounts for measurement overlap among cellular
      populations. Designing these models is now easier because of a new technique
      called high-definition t-SNE mapping. Nontrivial examples are provided that serve
      as a guide to create models that are consistent with data.

PMID- 29071674
TI  - Mass Cytometry Assays for Antigen-Specific T Cells Using CyTOF.
AB  - T Cells specific for a single antigen tend to be rare, even after expansion of
      memory cells. They are commonly detected by in vitro stimulation with peptides or
      protein, followed by staining for intracellular cytokines. In this protocol, we
      use CyTOF(r) mass cytometry to collect single-cell data on a large number of
      cytokines/chemokines, as well as cell-surface proteins that characterize T cells
      and other immune cells. We also include a method for magnetic bead enrichment of
      antigen-stimulated T cells, based on their expression of CD154 and CD69. Coupling
      magnetic enrichment with highly multi-parameter mass cytometry, this method
      enables the ability to dissect the frequency, phenotype, and function of antigen
      specific T cells in greater detail than previously possible. Rare cell subsets
      can be examined, while minimizing run times on the CyTOF.

PMID- 29071675
TI  - RNA Flow Cytometry Using the Branched DNA Technique.
AB  - The systematic modulation of mRNA and proteins governs the complicated and
      intermingled biological functions of our cells. Traditionally, transcriptomic
      technologies such as DNA microarray and RNA-Seq have been used to identify,
      characterize, and profile gene expression data. These are, however, considered
      bulk methods as they are unable to measure gene expression at the single-cell
      level, unless the cells are pre-sorted. Branched DNA is a flow cytometry-based
      detection platform that has been developed recently to measure mRNA at the single
      cell level. Originally adapted from microscopy, the current system has been
      modified to achieve compatibility with the detection of surface and intracellular
      antigens using monoclonal antibodies conjugated to fluorochromes, thus permitting
      simultaneous detection of mRNAs and proteins. The Branched DNA method offers a
      variety of advantages when compared to traditional or standard methods used for
      the quantification of mRNA, such as (a) the detection of specific mRNA on a per
      cell basis, (b) an alternate detection tool when the measurement of a protein is
      technically infeasible (i.e., no quality antibody exists) or the epitope is not
      assessable, and (c) correlate the analysis of mRNA with protein. Compared to
      earlier attempts at measuring nucleic acid by flow cytometry, the hybridization
      temperature applied in the Branched DNA assay is much lower, thus preserving the
      integrity of cellular structures for further characterization. It also has
      greatly increased specificity and sensitivity. Here, we provide detailed
      instruction for performing the Branched DNA method using it in a model system to
      correlate the expression of CD8 mRNA and CD8 protein by flow cytometry.

PMID- 29071676
TI  - Analysis of Individual Extracellular Vesicles by Flow Cytometry.
AB  - Extracellular vesicles (EVs) are released by cells and can be found in cell
      culture supernatants and biofluids. EVs carry proteins, nucleic acids, and other
      cellular components and can deliver these to nearby or distant cells, making EVs
      of interest as both disease biomarkers and therapeutic targets. EVs in biofluids
      are heterogeneous, coming from different cell types and from different sources
      with the cell, which limits the usefulness of bulk EV analysis methods that
      report the average features of all EVs present. Single-particle measurements such
      as flow cytometry would be preferred, but the small size and low abundance of
      surface antigens challenges conventional flow cytometry approaches, leading to
      the development of vesicle-specific assays and experimental design. Among the key
      issues that have emerged are: (a) judicious choice of detection (triggering)
      approach; (b) appropriate control experiments to confirm the vesicular nature of
      the detected events and the contribution of coincidence (aka swarm detection);
      and (c) the importance of fluorescence calibration to allow data to be compared
      over time and between laboratories. We illustrate these issues in the context of
      fluorescence-triggered Vesicle Flow Cytometry (VFC), a general approach to the
      quantitative measurement of EV number, size, and surface marker expression.

PMID- 29071677
TI  - Quantitative Fluorescence Measurements with Multicolor Flow Cytometry.
AB  - Multicolor flow cytometer assays are routinely used in clinical laboratories for
      immunophenotyping, monitoring disease and treatment, and determining prognostic
      factors. However, existing methods for quantitative measurements have not yet
      produced satisfactory results independent of flow cytometers used. This chapter
      details a procedure for quantifying surface and intracellular protein biomarkers
      by calibrating the output of a multicolor flow cytometer in units of antibodies
      bound per cell (ABC). The procedure includes the following critical steps: (a)
      quality control (QC) and performance characterization of the multicolor flow
      cytometer, (b) fluorescence calibration using hard dyed microspheres assigned
      with fluorescence intensity values in equivalent number of reference fluorophores
      (ERF), (c) compensation for correction of fluorescence spillover, and (d)
      application of a biological reference standard for translating the ERF scale to
      the ABC scale. The chapter also points out current efforts for implementing
      quantification of biomarkers in a manner which is independent of instrument
      platforms and reagent differences.

PMID- 29071678
TI  - High Throughput Flow Cytometry for Cell Surface Profiling.
AB  - Cell surface proteins are widely studied in the search for new biomarkers and
      therapeutic targets, but there is little information available about the
      surfaceome of individual cells, and this is difficult to obtain experimentally,
      especially in heterogeneous samples. Flow cytometry is a simple and robust tool
      for assessing cell surface protein expression on a single-cell level in a wide
      variety of cell types. However, due to the cost and relative scarcity of
      reagents, it is typically limited to interrogating known markers, screening small
      curated subsets of likely candidates, or validating targets obtained via other
      high throughput methods such as transcriptional profiling. Given recent advances
      in our understanding of stem cells, tumor-initiating cells, and other rare
      populations in seemingly homogenous samples, and the relative lack of correlation
      between the transcriptome and the surfaceome, large-scale flow cytometry screens
      have become an appealing option. A relatively exhaustive microarray-like flow
      cytometry screening platform can reveal unexpected markers or sub-populations
      that are not readily detected by other methods. The single-cell resolution,
      reliability, and simplicity of flow cytometry and the additional benefit of sub
      population/heterogeneity discrimination with the addition of functional and/or
      phenotypic co-stains allow for the rapid generation of very reliable data from a
      wide variety of samples at a low cost per sample. These larger datasets can be
      used for more elaborate bioinformatics, such as hierarchical clustering. Here we
      describe a method for high throughput cell surface profiling using conventional
      single or multicolor flow cytometry, which can be adapted to an antibody panel of
      any size.

PMID- 29071679
TI  - Multiparameter Conventional Flow Cytometry.
AB  - Multicolor flow cytometry is a useful technique when examining mixed populations
      of cells, such as blood and tissue cells in human and animal samples. The ability
      to use multiple fluorescent markers simultaneously allows for the identification
      of multiple cell types, as well as functional markers that further characterize
      each sample. The introduction of instruments capable of measuring 12-plus colors
      and new reagents has made this type of flow cytometry both popular and
      problematic. Adapting a typical staining panel from 4 to 6 color tubes to more
      than 12 colors is not simply a matter of "plug and play", but must be approached
      in a systematic manner to achieve a successful multi-parameter staining panel.
      This chapter will examine the considerations and methods needed to successfully
      perform multicolor flow cytometry.

PMID- 29071680
TI  - Multiparameter Intracellular Cytokine Staining.
AB  - Intracellular cytokine staining is a popular method for visualizing cellular
      responses, most often T-cell responses to antigenic or mitogenic stimulation. It
      can be coupled with staining for other functional markers, such as upregulation
      of CD107 or CD154, as well as phenotypic markers that define specific cellular
      subsets, e.g., effector and memory T-cell compartments, NK cells, or monocytes.
      Recent advances in multicolor flow cytometry instrumentation and software have
      allowed the routine combination of 12 or more markers, creating some technical
      and analytical challenges along the way, and exposing a need for standardization
      in the field. Here, we will review best practices for antibody panel design and
      procedural variables for multicolor intracellular cytokine staining, and present
      an optimized protocol with variations designed for use with specific markers and
      sample types.

PMID- 29071681
TI  - Multiparametric Analysis of Apoptosis by Flow Cytometry.
AB  - Flow cytometry is the most widely used method for detecting and quantifying
      apoptosis in mammalian cells. The multiparametric nature of flow cytometry allows
      several apoptotic characteristics to be combined in a single sample, making it a
      powerful tool for analyzing the complex progression of apoptotic death. This
      chapter provides guidelines for combining single-apoptosis assays such as
      fluorogenic caspase substrates, annexin V binding, DNA dye exclusion, and
      covalent viability probes into informative multiparametric assays. This
      multiparametric approach to analyzing apoptosis provides much more information
      than single-parameter assays that provide only a percentage apoptotic result,
      given that multiple early, intermediate, and late apoptotic stages can be
      observed and quantified simultaneously. While much more informative than single
      color assays, these multicolor methods can still be analyzed on relatively simple
      flow cytometers, making them accessible to many laboratories.

PMID- 29071682
TI  - Multiparameter Cell Cycle Analysis.
AB  - Cell cycle cytometry and analysis are essential tools for studying cells of model
      organisms and natural populations (e.g., bone marrow). Methods have not changed
      much for many years. The simplest and most common protocol is DNA content
      analysis, which is extensively published and reviewed. The next most common
      protocol, 5-bromo-2-deoxyuridine S phase labeling detected by specific
      antibodies, is also well published and reviewed. More recently, S phase labeling
      using 5'-ethynyl-2'-deoxyuridine incorporation and a chemical reaction to label
      substituted DNA has been established as a basic, reliable protocol. Multiple
      antibody labeling to detect epitopes on cell cycle regulated proteins, which is
      what this chapter is about, is the most complex of these cytometric cell cycle
      assays, requiring knowledge of the chemistry of fixation, the biochemistry of
      antibody-antigen reactions, and spectral compensation. However, because this
      knowledge is relatively well presented methodologically in many papers and
      reviews, this chapter will present a minimal Methods section for one mammalian
      cell type and an extended Notes section, focusing on aspects that are problematic
      or not well described in the literature. Most of the presented work involves how
      to segment the data to produce a complete, progressive, and compartmentalized
      cell cycle analysis from early G1 to late mitosis (telophase). A more recent
      development, using fluorescent proteins fused with proteins or peptides that are
      degraded by ubiquitination during specific periods of the cell cycle, termed
      "Fucci" (fluorescent, ubiquitination-based cell cycle indicators) provide an
      analysis similar in concept to multiple antibody labeling, except in this case
      cells can be analyzed while living and transgenic organisms can be created to
      perform cell cycle analysis ex or in vivo (Sakaue-Sawano et al., Cell 132:487
      498, 2007). This technology will not be discussed.

PMID- 29071684
TI  - Immunophenotypic Identification of Early Myeloerythroid Development.
AB  - Myeloerythroid-restricted precursor cells, derived from multipotent hematopoietic
      stem cells, give rise to mature cells of the granulocyte, monocyte, erythroid,
      and/or thrombocytic lineages. High-resolution profiling of the developmental
      stages, from hematopoietic stem cells to mature progeny, is important to be able
      to study and understand the underlying mechanisms that guide various cell fate
      decisions. Also, this approach opens for greater insights into pathogenic events
      such as leukemia, diseases that are most often characterized by halted
      differentiation at defined immature precursor levels. In this chapter, we provide
      protocols and discuss approaches concerning the analysis and purification of
      immature myeloerythroid lineages by multiparameter flow cytometry. A wealth of
      literature has demonstrated the feasibility of similar approaches also for the
      human system. However, in this chapter, we focus on the identification of bone
      marrow cells derived from C57BL/6 mice, in which flow cytometry-based
      immunophenotypic applications have been most widely developed. This should allow
      also for its application in genetically modified models on this background. For
      maximal reproducibility, all protocols described have been established using
      reagents from commercial vendors to be analyzed on a flow cytometer with factory
      standard configuration.

PMID- 29071685
TI  - Flow Cytometry Assays in Primary Immunodeficiency Diseases.
AB  - Inborn errors of immunity are the cause of the primary immunodeficiency diseases,
      an extremely diverse group of genetic defects that are inherited in Mendelian
      fashion and result in the impairment of development and/or function of key
      components of the immune system. Since the last publication of this chapter in
      2011, there have been approximately 100 new primary immunodeficiency diseases
      officially classified by the "Expert Committee for Primary Immunodeficiency" who
      met in 2015 and the numbers will continue to rise with the continued evolution
      and widespread adoption of genomic technologies. The ultimate diagnostic modality
      involves the identification of a mutation in a gene whose product is known to be
      involved in immunity. DNA sequencing is however still a rather time-consuming
      technology. Flow cytometry applications have evolved that are rapid, specific,
      and relatively inexpensive to screen for abnormalities associated with primary
      immunodeficiency diseases. The numerous flow cytometry procedures that have been
      developed to detect abnormalities in peripheral blood cells of primary
      immunodeficiency patients can barely be covered in an entire book, let alone one
      chapter. Instead of attempting to cover each disease with a specific assay or
      test, we will review four procedures each covering one of the three following
      broad forms of immune abnormalities observed in primary immunodeficiency, i.e.,
      immune subset abnormalities, immune marker abnormalities, and immune function
      abnormalities.

PMID- 29071686
TI  - Real-Time Deformability Cytometry: Label-Free Functional Characterization of
      Cells.
AB  - Real-time deformability cytometry (RT-DC) is a microfluidic technique that allows
      to capture and evaluate morphology and rheology of up to 1000 cells/s in a
      constricted channel. The cells are deformed without mechanical contact by
      hydrodynamic forces and are quantified in real-time without the need of
      additional handling or staining procedures. Segmented pictures of the cells are
      stored and can be used for further analysis. RT-DC is sensitive to alterations of
      the cytoskeleton, which allows, e.g., to show differences in cell cycle phases,
      identify different subpopulations in whole blood and to study mechanical
      stiffening of cells entering a dormant state. The abundance of the obtainable
      parameters and the interpretation as mechanical readout is an analytical
      challenge that needs standardization. Here, we will provide guidelines for
      measuring and post-processing of RT-DC data.

PMID- 29071683
TI  - Monitoring Cell Proliferation by Dye Dilution: Considerations for Probe
      Selection.
AB  - In the third edition of this series, we described protocols for labeling cell
      populations with tracking dyes, and addressed issues to be considered when
      combining two different tracking dyes with other phenotypic and viability probes
      for the assessment of cytotoxic effector activity and regulatory T cell
      functions. We summarized key characteristics of and differences between general
      protein and membrane labeling dyes, discussed determination of optimal staining
      concentrations, and provided detailed labeling protocols for both dye types.
      Examples of the advantages of two-color cell tracking were provided in the form
      of protocols for: (a) independent enumeration of viable effector and target cells
      in a direct cytotoxicity assay; and (b) an in vitro suppression assay for
      simultaneous proliferation monitoring of effector and regulatory T cells.The
      number of commercially available fluorescent cell tracking dyes has expanded
      significantly since the last edition, with new suppliers and/or new spectral
      properties being added at least annually. In this fourth edition, we describe
      evaluations to be performed by the supplier and/or user when characterizing a new
      cell tracking dye and by the user when selecting one for use in multicolor
      proliferation monitoring. These include methods for: (a) Assessment of the dye's
      spectral profile on the laboratory's flow cytometer(s) to optimize compatibility
      with other employed fluorochromes and minimize compensation problems; (b)
      Evaluating the effect of labeling on cell growth rate;

PMID- 29071687
TI  - Nuclear Cytometry: Analysis of the Patterns of DNA Synthesis and Transcription
      Using Flow Cytometry, Confocal Microscopy, and RNA Sequencing.
AB  - Eukaryotes are defined by cells that contain a nucleus and other membrane-bound
      organelles. Cytometric analysis in situ, utilizing imaging, provides a useful
      understanding of the structure and function of the various subcellular
      components, particularly when combined with methods that preserve the living
      state. In terms of information provided by the observation of eukaryotic nuclei,
      imaging has provided a wealth of information about cellular multiplication. When
      organisms are present in multicellular form (tissues and organs), this property
      does not generally confound imaging cytometry. Multicellular eukaryotic species
      present immediate problems when being considered for analysis using flow
      cytometry which requires suspensions of single particles. Although some
      eukaryotic cell types exist as natural single cell suspensions (cf. the
      erythropoietic system), for other tissues and organs, strategies are required to
      produce single particle suspensions. This chapter illustrates the application of
      flow cytometry combined with confocal microscopy to analyze complex organs,
      focusing on properties of the plant nucleus, and then goes on to describe how
      suspensions of nuclei can be prepared from tissues and organs, and used for flow
      cytometric analysis of cellular and transcriptional states. The application of
      these techniques to animal species is also discussed with the implication that
      this strategy is universally applicable for the characterization of nuclei within
      tissues that cannot readily be converted into suspensions of cells.

PMID- 29071688
TI  - Flow Cytometric FRET Analysis of Protein Interactions.
AB  - In the past decades, investigation of protein-protein interactions in situ in
      living or intact cells has gained expanding importance as structure/function
      relationships proposed from bulk biochemistry and molecular modeling experiments
      required confirmation at the cellular level. Forster (fluorescence) resonance
      energy transfer (FRET)-based methods are excellent tools for determining
      proximity and supramolecular organization of biomolecules at the cell surface or
      inside the cell. This could well be the basis for the increasing popularity of
      FRET. In fact, the number of publications exploiting FRET has exploded since the
      turn of the millennium. Interestingly, most applications are microscope-based,
      and only a fraction employs flow cytometry, even though the latter offers great
      statistical power owed to the potentially huge number of individually measured
      cells. However, with the increased availability of multi-laser flow cytometers,
      strategies to obtain absolute FRET efficiencies can now be relatively facilely
      implemented. In this chapter, we intend to provide generally useable protocols
      for measuring FRET in flow cytometry. After a concise theoretical introduction,
      recipes are provided for successful labeling techniques and measurement
      approaches. The simple, quenching-based population-level measurement, the classic
      ratiometric, intensity-based technique providing cell-by-cell actual FRET
      efficiencies, and a more advanced version of the latter, allowing for cell-by
      cell autofluorescence correction are described. An Excel macro pre-loaded with
      spectral data of the most commonly used fluorophores is also provided for easy
      calculation of average FRET efficiencies. Finally, points of caution are given to
      help design proper experiments and critically interpret the results.

PMID- 29071689
TI  - Overview of Fluorescence Lifetime Measurements in Flow Cytometry.
AB  - The focus of this chapter is time-resolved flow cytometry, which is broadly
      defined as the ability to measure the timing of fluorescence decay from excited
      fluorophores that pass through cytometers or high-throughput cell counting and
      cell sorting instruments. We focus on this subject for two main reasons: first,
      to discuss the nuances of hardware and software modifications needed for these
      measurements because currently, there are no widespread time-resolved cytometers
      nor a one-size-fits-all approach; and second, to summarize the application space
      for fluorescence lifetime-based cell counting/sorting owing to the recent
      increase in the number of investigators interested in this approach. Overall,
      this chapter is structured into three sections: (1) theory of fluorescence decay
      kinetics, (2) modern time-resolved flow cytometry systems, and (3) cell counting
      and sorting applications. These commentaries are followed by conclusions and
      discussion about new directions and opportunities for fluorescence lifetime
      measurements in flow cytometry.

PMID- 29071690
TI  - Overview of Lasers for Flow Cytometry.
AB  - Lasers are critical elements of all flow cytometers. Instrument capabilities are
      dictated by the wavelengths and characteristics of its laser sources. In this
      chapter, we review the lasers available for flow cytometry, and provide guidance
      in choosing laser wavelengths and characteristics to best match the analytical
      needs of biomedical research laboratories.

PMID- 29071691
TI  - Flow Cytometry: The Glass Is Half Empty.
AB  - In hopes of broadening the reader's perspective, this closing chapter discusses
      what flow cytometry cannot do; hence, the glass is half empty. Alternative
      methods using affordable and sustainable simple imaging cytometers are presented.

PMID- 29071692
TI  - David Sher on the Updated ASTRO Guidelines for Oropharyngeal Cancer.

PMID- 29071693
TI  - Changing Treatment Paradigms for Brain Metastases From Melanoma-Part 2: When and
      How to Use the New Systemic Agents.
AB  - Until recently, therapeutic strategies for melanoma brain metastases focused on
      local treatments: surgery, whole-brain radiation therapy, and stereotactic
      radiosurgery. Historically, systemic therapy had limited utility.
      Immunotherapeutic drugs, such as anti-cytotoxic T-lymphocyte-associated antigen 4
      and anti-programmed death 1 agents, and agents targeting the BRAF-MEK pathway
      have revolutionized the systemic treatment of melanoma brain metastases. Recent
      clinical trials of these agents have shown activity against melanoma brain
      metastases, and they are increasingly being used in clinical practice. In this
      article, we provide an overview of the currently available systemic agents,
      including immunotherapeutic agents and targeted tyrosine kinase inhibitors. We
      also provide a practical management algorithm to guide the practicing oncologist
      in the use of both of these new therapies and the more traditional local
      treatments.

PMID- 29071694
TI  - Large Scrotal Mass With Multifocal Intra-Abdominal, Retroperitoneal, and Pelvic
      Metastases.

PMID- 29071695
TI  - Newer Strategies for the Management of Low-Grade Gliomas.
AB  - Low-grade gliomas are infiltrative primary brain tumors that most commonly occur
      in young adults. They are relatively slow growing compared with high-grade
      gliomas. The World Health Organization classification system was updated in 2016
      to define low-grade gliomas using molecular markers in addition to histology. IDH
      mutation is an independent marker associated with better outcomes. Management is
      individualized based on tumor histology, molecular characterization, and patient
      risk factors. Given the longer course and natural history of low-grade gliomas,
      the goals of treatment should be to prolong overall survival and minimize
      neurocognitive decline. Early maximum safe resection is the first line of
      treatment. While low-risk patients may be followed with observation after
      surgery, patients with high-risk factors (subtotal resection, age > 40 years, IDH
      wild-type tumors) should be treated with radiation and chemotherapy. Improved
      understanding of the molecular characteristics of low-grade gliomas will further
      guide risk stratification and allow the identification of treatment approaches
      that are more effective and less toxic.

PMID- 29071696
TI  - Diagnosing and Managing Delirium in Cancer Patients.
AB  - Delirium is frequently encountered when caring for cancer patients, from initial
      diagnosis to the advanced stages of the disease; however, it is often missed.
      Oncologists need to be familiar with the various defining features of the
      condition, and should be able to identify common underlying causes. We present a
      systematic approach to the workup, as well as pharmacologic and nonpharmacologic
      approaches to management. We discuss the common practice of treatment with
      neuroleptics, as well as recent controversy surrounding their use.

PMID- 29071697
TI  - Systematic review of Spanish outcome measures on motor imagery ability: use in
      physical rehabilitation.
AB  - INTRODUCTION: Motor imagery is a mental representation of movement without any
      body movement and its training accelerates motor learning and improves motor
      skills. A thorough understanding of how to manipulate mental images is necessary
      before using motor imagery in physical rehabilitation. This systematic review
      analyzes the psychometric properties of the outcome measures on motor imagery
      ability for the Spanish-speaking people and discusses its usefulness in people
      with motor disabilities. MATERIALS AND METHODS: A review was conducted, using the
      COSMIN checklist to appraise 19 articles on measurement properties of motor
      imagery ability assessments found in reviewed databases. The criteria for grading
      the usefulness of instruments to measure motor imagery was established depending
      on the sensory modality assessed. We found 17 questionnaires. RESULTS:
      Methodological quality was mostly fair in reliability and validity. Four tests
      have been considered highly useful in assessing motor imagery. MIQ (alpha = 0.90;
      EFA=2) and MIQ-R (alpha = 0.84; EFA=2) are the best suited to evaluate motor
      imagery in Spanish-speaking population. To handle spatial images, MASMI (alpha =
      0.93) or MARMI (alpha = 0.90) tests may be more beneficial. CONCLUSIONS: MIQ and
      MIQ-R evaluate visual and kinesthetic imagery, but these are difficult to use in
      the physical rehabilitation of people with motor disabilities. Currently, there
      are no valid Spanish translations of studies regarding motor imagery outcome
      measures for people with disabilities.

PMID- 29071698
TI  - [Movement disorders units and management of motor fluctuations in advanced
      Parkinson's disease].
AB  - INTRODUCTION: Advanced Parkinson's disease (PD) entails complications, such as
      motor fluctuations. In Spain, medical attention for such cases is often provided
      in movement disorder units (MDU). AIM: To gain further knowledge of the
      diagnostic resources and therapeutic approach of MDU. SUBJECTS AND METHODS: A
      descriptive cross-sectional study was conducted. The researchers designed an on
      line questionnaire, addressed to neurologists from MDUs, containing 48 questions
      about the resources they have available, the number of patients with PD and motor
      fluctuations that have been attended to, as well as the therapeutic approach,
      according to the Hoehn and Yahr (HY) scale. RESULTS: Fifty-five neurologists
      participated. Structural neuroimaging is available to 100% of them; 89% have
      access to functional neuroimaging; 89% have acute pharmacological tests available
      for use; 78% have access to genetic tests; and 53% have transcranial ultrasound
      at their disposal. There are 2.5 neurologists and 1.2 nurses per unit. Of the
      patients with PD that they see, 19% of them are in HY stage 1, 59% are in HY
      stage 2-3 and 22% are in HY stage 4-5. Treatment consists, first of all, in
      monoamine oxidase type B inhibitors in HY stages 1 and 2, and levodopa in HY
      stages 3, 4 and 5. Twenty-four per cent of the patients have motor fluctuations,
      with 5.5 off episodes per day, lasting 44 minutes, with a total of seven off
      hours per day. Fourteen per cent of the patients under 70 years of age with more
      than three long-term off episodes per day are receiving invasive treatment for
      motor fluctuations. CONCLUSIONS: MDUs are well equipped with diagnostic and
      pharmacological resources. Pharmacological treatments are tailored to each
      patient with a wide range of combinations. Despite this optimisation, the
      prevalence of motor fluctuations is still high in advanced patients, and invasive
      therapies may be underused.

PMID- 29071699
TI  - [Cognitive impairment as a predictor of functional decline after hospitalization:
      DECOFIRH Study].
AB  - AIM: Cognitive impairment is underdiagnosed in the elderly. We aimed to study the
      rate of positive responses to an informant-based questionnaires and functional
      disability after hospital discharge. PATIENTS AND METHODS: Observational
      prospective case series of patients aged 70-85 years-old admitted for
      hospitalization in an Internal Medicine ward. All medical records were reviewed
      and those patients with no previous diagnosis of dementia or related neurological
      conditions, no previous recent hospitalization or not having a caregiver were
      evaluated after signing an informed consent. A medical interview including the
      Alzheimer's Disease 8 (AD8), the Informant Questionnaire on Cognitive Decline in
      the Elderly (IQCODE) and Barthel Index was completed. Barthel Index was obtained
      three months after discharge. RESULTS: During a 3-month period a total of 809
      admissions were screened and 79 (9.7%) fulfilled the study criteria. Patient's
      mean age was 80 years-old. Common comorbidities were arterial hypertension
      (83.5%), major surgery (54.4%) and heart disorders (50.6%). The most frequent
      cause of admission was infectious disease (37.9%). Test positivity for cognitive
      impairment was 30.3% for IQCODE and 34.1% for AD8. At admission 37.9% of the
      patients were functionally independent. At three months this percentage dropped
      to 24%. CONCLUSIONS: In this small sample size, almost a third of older patients,
      without major comorbidities or neurological disorders, admitted to a general
      hospital showed an informant-based suggestion of cognitive impairment previously
      undiagnosed. Functional impairment affects almost a quarter of these patients
      three months after admission.

PMID- 29071700
TI  - [Treatment of encephalopathy by means of valproic acid with carglumic acid: two
      case reports and a review of the literature].
AB  - INTRODUCTION: Valproic acid (VPA) is a drug mainly used to treat epilepsy.
      Hyperammonaemic encephalopathy due to VPA is a rare but serious complication. The
      mechanism by which VPA influences the increase in ammonia consists in blocking
      the urea cycle, thereby inhibiting N-acetylglutamate synthase and diminishing
      acetyl coenzyme A. Generally, the treatment employed has been to withdraw VPA and
      to administer arginine, carnitine, antibiotics, glucose and protein restriction.
      Previous experience with carglumic acid is limited to reports of isolated cases
      of paediatric patients. CASE REPORTS: We report the cases of two adult patients
      with encephalopathy due to VPA who were treated with carglumic acid, in addition
      to the conventional measures. Following treatment with the drug, ammonia levels
      can be seen to return to normal values. In one of the two cases, owing to the
      existence of another cause of encephalopathy, no clinical improvement was
      observed. CONCLUSIONS: From the biochemical point of view, treating
      encephalopathy due to VPA with carglumic acid is a logical step, as it reverses
      the blockage of the urea cycle conditioned by VPA. The mechanism proposed as
      being the one by which brain toxicity and, therefore, encephalopathy are produced
      is the passage of ammonia in the form of glutamine to the inside of the cell,
      which then returns to ammonia and glutamate in the mitochondria and leads to
      oxidative stress. Carglumic acid must be considered an important part of the
      treatment in adult patients with hyperammonaemic encephalopathy due to VPA,
      although a randomised clinical trial needs to be conducted with the drug in order
      to test its efficacy.

PMID- 29071702
TI  - [XXXI Reunion Anual de la Sociedad Neurologica de Castilla y Leon.
      Communications].

PMID- 29071701
TI  - [The hypothalamus in Huntington's disease].
AB  - INTRODUCTION: Disorders affecting sleep and the circadian rhythm, autonomic
      clinical signs and symptoms, and neuroendocrine alterations are frequent
      characteristics in Huntington's disease, some of which present in early stages of
      the disease. It is reasonable to think that some of these features could result
      from a hypothalamic dysfunction affecting the centre regulating sleep, metabolism
      and the autonomic nervous system. AIM: The study presents the evidence available
      to date that suggests the involvement of a hypothalamic disorder in Huntington's
      disease. DEVELOPMENT: Histopathological, hormonal and neuroimaging research
      relates this area of the brain to Huntington's disease. The experimental findings
      and those obtained with animal models or in studies conducted with patients are
      summarised. Likewise, the clinical repercussions (sleep and circadian rhythm
      disorders, psychiatric and cognitive pathologies, and the clinical signs and
      symptoms linked to autonomic dysfunction) secondary to possible involvement of
      the hypothalamus in this disease are also described. CONCLUSIONS: The
      hypothalamus acts as a centre that integrates the neuroendocrine and autonomic
      functions, and plays a significant role in cognitive and behavioural signs and
      symptoms. Disorders of this type have been highlighted in Huntington's disease.
      Further studies are needed to elucidate the role and scope of this region of the
      brain in this disease.

PMID- 29071703
TI  - [West syndrome associated with 14q12 duplication].

PMID- 29071704
TI  - [Cervantes and Parkinson's disease].

PMID- 29071705
TI  - Vigilance for threat accounts for inter-individual variation in physiological
      responses to adversity in rhesus macaques: A cognition * environment approach.
AB  - Early life adversity (ELA) can lead to poor health later in life. However, there
      is significant variation in outcomes, with some individuals displaying resilience
      even in the face of adversity. Using longitudinal data collected from free
      ranging rhesus macaques between birth and 3 years, we examined whether individual
      variation in vigilance for threat, an early emerging attentional bias, can
      account for variation in long-term outcomes between individuals reared in similar
      environments. We found that ELA and vigilance during infancy interact to predict
      physiological dysregulation in Sympathetic Nervous System (SNS) and Hypothalamic
      Pituitary-Adrenal (HPA) stress responses during juvenility. During high stress
      periods, High ELA juveniles with high vigilance exhibit less asymmetry than High
      ELA juveniles with low vigilance. This suggests that although increased vigilance
      is viewed as a negative consequence of ELA, it might also be a mechanism by which
      vulnerable individuals proactively buffer themselves from negative outcomes in
      unstable or threatening environments.

PMID- 29071706
TI  - Behavioral flexibility in learning to sit.
AB  - What do infants learn when they learn to sit upright? We tested behavioral
      flexibility in learning to sit-the ability to adapt posture to changes in the
      environment-in 6- to 9-month-old infants sitting on forward and backward slopes.
      Infants began with slant at 0 degrees ; then slant increased in 2 degrees 
      increments until infants lost balance. Infants kept balance on impressively steep
      slopes, especially in the forward direction, despite the unexpected movements of
      the apparatus. Between slant adjustments while the slope was stationary, infants
      adapted posture to the direction and degree of slant by leaning backward on
      forward slopes and forward on backward slopes. Postural adaptations were nearly
      optimal for backward slopes. Sitting experience predicted greater postural
      adaptations and increased ability to keep balance on steeper changes of slant,
      but only for forward slopes. We suggest that behavioral flexibility is integral
      to learning to sit and increases with sitting experience.

PMID- 29071707
TI  - The influence of grasping habits and object orientation on motor planning in
      children and adults.
AB  - We investigated the influence of habitual grasp strategies and object orientation
      on motor planning in 3-year-olds and 4- to 5-year-old children and adults.
      Participants were required to rotate different vertically oriented objects around
      180 degrees . Usually, adults perform this task by grasping objects with an
      awkward grip (thumb and index finger pointing downward) at the beginning of the
      movement, in order to finish it with a comfortable hand position. This pattern
      corresponds to the well-known end-state comfort effect (ESC) in grasp planning.
      The presented objects were associated with different habitual grasp orientations
      that either corresponded with the grasp direction required to reach end-state
      comfort (downward) or implied a contrary grasp orientation (upward).
      Additionally, they were presented either in their usual, canonical orientation
      (e.g., shovel with the blade oriented downward versus cup with its opening
      oriented upward) or upside down. As dependent variable we analyzed the number of
      grips conforming to the end-state comfort principle (ESC score) realized in each
      object type and orientation condition. The number of grips conforming to ESC
      strongly increased with age. In addition, the extent to which end-state comfort
      was considered was influenced by the actual orientation of the objects'
      functional parts. Thus, in all age-groups the ESC score was highest when the
      functional parts of the objects were oriented downward (shovel presented
      canonically with blade pointing downward, cup presented upside down) and
      corresponded to the hand orientation needed to realize ESC.

PMID- 29071709
TI  - The evolution of costly mate choice against segregation distorters.
AB  - The evolution of female preference for male genetic quality remains a
      controversial topic in sexual selection research. One well-known problem, known
      as the lek paradox, lies in understanding how variation in genetic quality is
      maintained in spite of natural selection and sexual selection against low-quality
      alleles. Here, we theoretically investigate a scenario where females pay a direct
      fitness cost to avoid males carrying an autosomal segregation distorter. We show
      that preference evolution is greatly facilitated under such circumstances.
      Because the distorter is transmitted in a non-Mendelian fashion, it can be
      maintained in the population despite directional sexual selection. The preference
      helps females avoid fitness costs associated with the distorter. Interestingly,
      we find that preference evolution is limited if the choice allele induces a very
      strong preference or if distortion is very strong. Moreover, the preference can
      only persist in the presence of a signal that reliably indicates a male's
      distorter genotype. Hence, even in a system where the lek paradox does not play a
      major role, costly preferences can only spread under specific circumstances. We
      discuss the importance of distorter systems for the evolution of costly female
      choice and potential implications for the use of artificial distorters in pest
      control.

PMID- 29071708
TI  - Men Lacking a Caregiver Have Greater Risk of Long-Term Nursing Home Placement
      After Stroke.
AB  - BACKGROUND/OBJECTIVES: Social support can prevent or delay long-term nursing home
      placement (NHP). The purpose of our study was to understand how the availability
      of a caregiver can affect NHP after ischemic stroke and how this affects
      different subgroups differently. DESIGN: Nested cohort study. SETTING: Nationally
      based REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
      PARTICIPANTS: Stroke survivors aged 65 to 100 (256 men, 304 women). MEASUREMENTS:
      Data were from Medicare claims from January 2003 to December 2013 and REGARDS
      baseline interviews conducted from January 2003 to October 2007. Caregiver
      support was measured by asking, "If you had a serious illness or became disabled,
      do you have someone who would be able to provide care for you on an on-going
      basis?" Diagnosis of ischemic stroke was derived from inpatient claims. NHP was
      determined using a validated claims algorithm for stays of 100 days and longer.
      Risk was estimated using Cox regression. RESULTS: Within 5 years of stroke, 119
      (21.3%) participants had been placed in a nursing home. Risk of NHP was greater
      in those lacking available caregivers (log-rank P = .006). After adjustment for
      covariates, lacking an available caregiver increased the risk of NHP after stroke
      within 1 year by 70% (hazard ratio (HR) = 1.70, 95% confidence interval (CI) =
      0.97-2.99) and within 5 years by 68% (HR = 1.68, 95% CI = 1.10-2.58). The effect
      of caregiver availability on NHP within 5 years was limited to men (HR = 3.15,
      95% CI = 1.49-6.67). CONCLUSION: In men aged 65 and older who have survived an
      ischemic stroke, the lack of an available caregiver is associated with triple the
      risk of NHP within 5 years.

PMID- 29071710
TI  - Microbiota Replacement Therapies: Innovation in Gastrointestinal Care.
AB  - There has been an increasing interest in the association between human disease
      and altered gut microbiota, and therapeutics to modulate microbiota to treat
      disease. Healthy human gastrointestinal microbiota is highly diverse and rich,
      and harbors between 500 and 2,000 species. Diseases associated with dysbiotic
      microbiota include antibiotic-associated diarrhea, Clostridium difficile
      infection, multidrug-resistant organisms, inflammatory bowel disease, obesity,
      metabolic syndrome, diabetes mellitus, neuropsychiatric diseases, and systemic
      autoimmune diseases. Microbiota replacement therapies have shown immense promise
      in treatment of recurrent C. difficile infection and are being studied for other
      indications. Microbiota replacement therapies for indications other than C.
      difficile infection should be performed only in research settings. There is an
      immense need for standardized microbiota replacement therapies for C. difficile
      infection. Studies are needed to elucidate long-term safety and adverse events
      from these therapies.

PMID- 29071711
TI  - A quantitative approach for analysing bone modelling patterns from craniofacial
      surfaces in hominins.
AB  - Bone size and shape arise throughout ontogeny as a result of the coordinated
      activity of osteoblasts and osteoclasts, responsible for bone deposition and
      resorption, and growth displacements. The modelling processes leave specific
      microstructural features on the bone surface, which can be used to infer the
      mechanisms shaping craniofacial traits in extinct and extant species. However,
      the analysis of bone surfaces from fossils and archaeological samples faces some
      difficulties related to the bone loss caused by taphonomic factors, and the lack
      of formal methods for estimating missing information and comparing the patterns
      of bone modelling among several specimens and samples. The present study provides
      a new approach for the quantitative analysis of bone formation and resorption
      patterns obtained from craniofacial surfaces. First, interpolation techniques
      were used to estimate missing data on high-resolution replicas of the left
      maxilla in a sample of sub-adult and adult modern humans and sub-adult fossil
      hominins. The performance of this approach was assessed by simulating variable
      amounts of missing data. Then, we applied measures of dispersion and central
      tendency to represent the variation and average pattern of bone modelling within
      samples. The spatial interpolation resulted in reliable estimations of the type
      of cell activity (deposition or resorption) in the missing areas, even when large
      extensions of the bone surface were lost. The quantification of the histological
      data allowed us to integrate the information of different specimens and depict
      the areas with higher and lower variation in the bone modelling pattern of the
      maxilla among specimens. Overall, the main advantages of the quantitative
      approach used here for generating bone modelling patterns are the high
      replicability and the possibility of incorporating variation among specimens into
      the comparisons among samples.

PMID- 29071712
TI  - The role of the microbiome in psoriasis: moving from disease description to
      treatment selection?
AB  - BACKGROUND: With several million microbes per square centimetre of skin, the task
      of mapping the physiological cutaneous microbiome is enormous. Indeed, the
      reliance on bacterial culture to identify cutaneous bacterial communities has led
      to a systematic underappreciation of cutaneous microbial diversity, potentially
      limiting our understanding of common inflammatory skin diseases, including
      psoriasis. However, based heavily on developments in molecular biology and
      bioinformatics, including next-generation sequencing, the last decade has
      witnessed a marked increase in our understanding of the extent and composition of
      the cutaneous microbiome. It is already clear that skin-specific (skin site and
      skin microenvironment), individual-specific (hygiene, sex, age and hormonal
      status), disease-specific (atopic eczema, acne) and genetic factors can all
      influence the cutaneous microbiome, albeit to varying and, as yet, ill-defined
      extents. OBJECTIVES: To investigate the role of the microbiome in psoriasis and
      to outline how microbiome studies can be harnessed to provide new insights into
      disease pathogenesis and treatment selection. METHODS: This review briefly
      describes the process of 16S ribosomal RNA sequencing and then charts our current
      understanding of the cutaneous microbiome in health and the alterations
      (dysbiosis) associated with chronic inflammatory diseases, with particular
      reference to psoriasis. RESULTS: The possibility and clinical relevance of
      intraindividual cross-talk between the various microbiomes is discussed and
      potential mechanisms underpinning the interactions between resident skin flora
      and the immune system are highlighted. CONCLUSIONS: Ultimately, in the age of
      personalized medicine, the integration of cutaneous microbiome signatures and
      comprehensive disease and drug response endotypes will herald a novel approach in
      the clinical management of chronic multisystem inflammatory diseases.

PMID- 29071713
TI  - Imaging connected porosity of crystalline rock by contrast agent-aided X-ray
      microtomography and scanning electron microscopy.
AB  - We set out to study connected porosity of crystalline rock using X-ray
      microtomography and scanning electron microscopy with energy dispersive X-ray
      spectroscopy (SEM-EDS) with caesium chloride as a contrast agent. Caesium is an
      important radionuclide regarding the final deposition of nuclear waste and also
      forms dense phases that can be readily distinguished by X-ray microtomography and
      SEM-EDS. Six samples from two sites, Olkiluoto (Finland) and Grimsel
      (Switzerland), where transport properties of crystalline rock are being studied
      in situ, were investigated using X-ray microtomography and SEM-EDS. The samples
      were imaged with X-ray microtomography, immersed in a saturated caesium chloride
      (CsCl) solution for 141, 249 and 365 days and imaged again with X-ray
      microtomography. CsCl inside the samples was successfully detected with X-ray
      microtomography and it had completely penetrated all six samples. SEM-EDS
      elemental mapping was used to study the location of caesium in the samples in
      detail with quantitative mineral information. Precipitated CsCl was found in the
      connected pore space in Olkiluoto veined gneiss and in lesser amounts in Grimsel
      granodiorite. Only a very small amount of precipitated CsCl was observed in the
      Grimsel granodiorite samples. In Olkiluoto veined gneiss caesium was found in
      pinitised areas of cordierite grains. In the pinitised areas caesium was found in
      notable excess compared to chloride, possibly due to the combination of small
      pore size and negatively charged surfaces. In addition, elevated concentrations
      of caesium were found in kaolinite and sphalerite phases. The findings concerning
      the location of CsCl were congruent with X-ray microtomography.

PMID- 29071715
TI  - Algorithmic structural segmentation of defective particle systems: a lithium-ion
      battery study.
AB  - We describe a segmentation algorithm that is able to identify defects (cracks,
      holes and breakages) in particle systems. This information is used to segment
      image data into individual particles, where each particle and its defects are
      identified accordingly. We apply the method to particle systems that appear in Li
      ion battery electrodes. First, the algorithm is validated using simulated data
      from a stochastic 3D microstructure model, where we have full information about
      defects. This allows us to quantify the accuracy of the segmentation result. Then
      we show that the algorithm can successfully be applied to tomographic image data
      from real battery anodes and cathodes, which are composed of particle systems
      with very different morpohological properties. Finally, we show how the results
      of the segmentation algorithm can be used for structural analysis.

PMID- 29071714
TI  - DNER and NFIA are expressed by developing and mature AII amacrine cells in the
      mouse retina.
AB  - The present study has taken advantage of publicly available cell type specific
      mRNA expression databases in order to identify potential genes participating in
      the development of retinal AII amacrine cells. We profile two such genes,
      Delta/Notch-like EGF repeat containing (Dner) and nuclear factor I/A (Nfia), that
      are each heavily expressed in AII amacrine cells in the mature mouse retina, and
      which conjointly identify this retinal cell population in its entirety when using
      antibodies to DNER and NFIA. DNER is present on the plasma membrane, while NFIA
      is confined to the nucleus, consistent with known functions of each of these two
      proteins. DNER also identifies some other subsets of retinal ganglion and
      amacrine cell types, along with horizontal cells, while NFIA identifies a subset
      of bipolar cells as well as Muller glia and astrocytes. During early postnatal
      development, NFIA labels astrocytes on the day of birth, AII amacrine cells at
      postnatal (P) day 5, and Muller glia by P10, when horizontal cells also
      transiently exhibit NFIA immunofluorescence. DNER, by contrast, is present in
      ganglion and amacrine cells on P1, also labeling the horizontal cells by P10.
      Developing AII amacrine cells exhibit accumulating DNER labeling at the dendritic
      stalk, labeling that becomes progressively conspicuous by P10, as it is in
      maturity. This developmental time course is consistent with a prospective role
      for each gene in the differentiation of AII amacrine cells.

PMID- 29071716
TI  - Sensitivity to facial expressions among extremely low birth weight survivors in
      their 30s.
AB  - The current study investigated the impact of birth weight on the ability to
      recognize facial expressions in adulthood among the longest known prospectively
      followed cohort of extremely low birth weight survivors (ELBW; <1,000 g). We
      measured perceptual threshold to detect subtle facial expressions and confusion
      among different emotion categories in order to disentangle visual perceptual
      ability from emotional processing. ELBW adults (N = 64, Mage  = 31.9 years) were
      more likely than normal birth weight (NBW) controls (N = 82, Mage  = 32.5 years)
      to see fear in angry faces. This finding was not a result of increased perceptual
      efficiency in processing fearful expressions in the ELBW adults, since the two
      groups did not differ on their threshold to detect emotion in low intensity
      facial expressions. These findings suggest that a processing bias toward fear may
      reflect long-term developmental effects from being born at ELBW that may portend
      socioemotional problems that characterize ELBW survivors.

PMID- 29071718
TI  - Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory
      Analysis of Confirmatory Phase III Trials Used for Marketing Approval.
AB  - The results of pivotal trials, which provide a rationale for marketing approval
      decisions for new drugs, are considered for various comparative purposes in
      postmarketing analyses. Using meta-regression analysis of 91 randomized
      controlled trials of 61 approved antihypertensive drugs in Japan, we show that
      mean baseline blood pressure (BP) of each arm was associated with predetermined
      entry criteria (EC), age, and trial start year (TSY). BP changes following
      treatment were associated with EC, subject characteristics (e.g., age,
      complications, baseline BP), study design (e.g., concomitant drug use), and TSY.
      Effect sizes were generally larger in trials for the first and second drugs in
      the same class than in trials for follow-on drugs. Results of pivotal trials may
      vary depending on many factors, suggesting possible challenges associated with
      the comparison of these results indirectly. Due to the heterogeneity in pivotal
      trials, caution should be exercised when comparing approved drugs and conducting
      meta-analyses retrospectively.

PMID- 29071717
TI  - SOX8 regulates cancer stem-like properties and cisplatin-induced EMT in tongue
      squamous cell carcinoma by acting on the Wnt/beta-catenin pathway.
AB  - A sub-population of chemoresistant cells exhibits biological properties similar
      to cancer stem cells (CSCs), and these cells are believed to be a main cause for
      tumor relapse and metastasis. In our study, we explored the role of SOX8 and its
      molecular mechanism in the regulation of the stemness properties and the
      epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous
      cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin
      resistant TSCC cells, which displayed CSC-like properties and exhibited EMT. SOX8
      was also overexpressed in chemoresistant patients with TSCC and was associated
      with higher lymph node metastasis, advanced tumor stage and shorter overall
      survival. Stable knockdown of SOX8 in cisplatin-resistant TSCC cells inhibited
      chemoresistance, tumorsphere formation, and EMT. The Wnt/beta-catenin pathway
      mediated the cancer stem-like properties in cisplatin-resistant TSCC cells.
      Further studies showed that the transfection of active beta-catenin in SOX8
      stable-knockdown cells partly rescued the SOX8 silencing-induced repression of
      stem-like features and chemoresistance. Through chromatin immunoprecipitation and
      luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled
      7 (FZD7) and induced the FZD7-mediated activation of the Wnt/beta-catenin
      pathway. In summary, SOX8 confers chemoresistance and stemness properties and
      mediates EMT processes in chemoresistant TSCC via the FZD7-mediated Wnt/beta
      catenin pathway.

PMID- 29071719
TI  - Medications That Cause Dry Mouth As an Adverse Effect in Older People: A
      Systematic Review and Metaanalysis.
AB  - OBJECTIVES: To assess and quantify the risk of drug-induced dry mouth as a side
      effect in older people. DESIGN: Systematic review and metaanalysis. SETTING: A
      search of the literature was undertaken using Medline, Embase, Cochrane, Web of
      Science, and PubMed from 1990 to 2016. PARTICIPANTS: Older people (aged >=60) who
      participated in intervention or observational studies investigating drug use as
      an exposure and xerostomia or salivary gland hypofunction as adverse drug
      outcomes. MEASUREMENTS: Two pairs of authors screened titles and abstracts of
      studies for relevance. Two authors independently extracted data, including study
      characteristics, definitions of exposure and outcome, and methodological quality.
      For the metaanalyses, random-effects models were used for pooling the data and I2
      statistics for exploring heterogeneity. RESULTS: Of 1,544 potentially relevant
      studies, 52 were deemed eligible for inclusion in the final review and 26 in
      metaanalyses. The majority of studies were of moderate methodological quality. In
      the intervention studies, urological medications (odds ratio (OR) = 5.91, 95%
      confidence interval (CI) = 4.04-8.63; I2  = 62%), antidepressants (OR = 4.74, 95%
      CI = 2.69-8.32, I2  = 21%), and psycholeptics (OR = 2.59, 95% CI = 1.79-3.95, I2 
      = 0%) were significantly associated with dry mouth. In the observational studies,
      numbers of medications and several medication classes were significantly
      associated with xerostomia and salivary gland hypofunction. CONCLUSION:
      Medication use was significantly associated with xerostomia and salivary gland
      hypofunction in older adults. The risk of dry mouth was greatest for drugs used
      for urinary incontinence. Future research should develop a risk score for
      medication-induced dry mouth to assist with prescribing and medication
      management.

PMID- 29071720
TI  - Antituberculosis Drug-Induced Adverse Events in the Liver, Kidneys, and Blood:
      Clinical Profiles and Pharmacogenetic Predictors.
AB  - Antituberculosis drug-induced adverse drug reactions (ATD-ADRs) are increasing
      globally, and it is key to identify candidate ATD-ADRs loci for clinical
      management. We prospectively enrolled 1,235 highly suspicious tuberculosis (TB)
      inpatients to investigate the profiles and genetic risk factors of ATD-ADRs in
      the liver, kidneys, and blood. Overall, 644 subjects were eligible and genotyped
      for seven polymorphisms in drug-metabolizing enzymes and transporter genes.
      Clinical follow-up and blood analysis were performed regularly. We found that a
      notable rate of ATD-ADRs (incidence: 16.5%, drug intervention rate: 10.4%),
      mainly involving hepatotoxicity (10.6%) and leukopenia (3.3%) in western China.
      CYP2D6 rs1135840 and NUDT15 rs116855232 increased the risks of hepatotoxicity and
      leukopenia with an odds ratio of 2.52 and 4.97, respectively. Both variants
      showed excellent negative predictive values (93.7% and 98.1%, respectively) but
      moderate sensitivities (72.7% and 52.4%, respectively). These data provide new
      insight into ATD-ADRs in the Chinese population and may offer future leads for
      diagnosis and treatment.

PMID- 29071722
TI  - Research Review: Gender identity in youth: treatment paradigms and controversies.
AB  - BACKGROUND: Pediatric gender identity has gained increased attention over the
      past several years in the popular media, political arena, and medical literature.
      This article reviews terminology in this evolving field, traditional models of
      gender identity development and their limitations, epidemiology and natural
      history of cross-gender identification among children and adolescents, co
      occurring conditions and behaviors, research into the biological and psychosocial
      determinants of cross-gender identification, and research into the options
      regarding and benefits of clinical approaches to gender incongruent youth.
      METHODS: Based on a critical review of the extant literature, both theoretical
      and empirical, that addresses the issue of pediatric gender identity, the authors
      synthesized what is presently known and what is in need of further research in
      order to elucidate the developmental trajectory and clinical needs of gender
      diverse youth. RESULTS: The field of pediatric gender identity has evolved
      substantially over the past several years. New research suggests that cross
      gender identification is prevalent (approximately 1% of youth). These youth
      suffer disproportionately high rates of anxiety, depression, and suicidality.
      Although research into the etiology of cross-gender identification is limited,
      emerging data have shown that affirmative treatment protocols may improve the
      high rates of mental health difficulties seen among these patients. CONCLUSIONS:
      The field of pediatric gender identity has evolved dramatically. Emerging data
      suggest that these patients' high rates of anxiety, depression, and suicidality
      appear to be improved with affirmative protocols, although future longitudinal
      data are needed.

PMID- 29071721
TI  - Erythrocyte membrane fatty acids and breast cancer risk: a prospective analysis
      in the nurses' health study II.
AB  - The roles of specific fatty acids in breast cancer etiology are unclear,
      particularly among premenopausal women. We examined 34 individual fatty acids,
      measured in blood erythrocytes collected between 1996 and 1999, and breast cancer
      risk in a nested case-control study of primarily premenopausal women in the
      Nurses' Health Study II. Breast cancer cases diagnosed after blood collection and
      before June 2010 (n = 794) were matched to controls and conditional logistic
      regression was used to estimate OR's (95% CI's) for associations of fatty acids
      with breast cancer; unconditional logistic regression was used for stratified
      analyses. Fatty acids were not significantly associated with breast cancer risk
      overall; however, heterogeneity by body mass index (BMI) was observed. Among
      overweight/obese women (BMI >= 25), several odd-chain saturated (SFA, e.g. 17:0,
      ORQ4vsQ1 (95% CI) =1.85 (1.18-2.88), ptrend =0.006 pint <0.001), trans (TFA, e.g.
      18:1, ORQ4vsQ1 (95% CI) =2.33 (1.45-3.77), ptrend <0.001, pint =0.007) and dairy
      derived fatty acids (SFA 15:0 + 17:0 + TFA 16:1n-7t; ORQ4vsQ1 (95% CI) =1.83(1.16
      2.89), ptrend =0.005, pint <0.001) were positively associated, and n-3
      polyunsaturated fatty acids (n-3 PUFA, e.g. alpha-linolenic acid; ORQ4vsQ1 (95%
      CI) =0.57 (0.36-0.89), ptrend =0.017, pint =0.03) were inversely associated with
      breast cancer. Total SFA were inversely associated with breast cancer among women
      with BMI < 25 (ORQ4vsQ1 (95% CI) =0.68 (0.46-0.98), ptrend =0.05, pint =0.01).
      Thus, while specific fatty acids were not associated with breast cancer overall,
      our findings suggest positive associations of several SFA, TFA and dairy-derived
      fatty acids and inverse associations of n-3 PUFA with breast cancer among
      overweight/obese women. Given these fatty acids are influenced by diet, and
      therefore are potentially modifiable, further investigation of these associations
      among overweight/obese women is warranted.

PMID- 29071724
TI  - Risk factors for fetomaternal bleeding after laser therapy for twin-twin
      transfusion syndrome.
AB  - OBJECTIVE: To quantify and assess potential risk factors for transplacental
      passage of fetal red blood cells (RBCs) into the maternal circulation
      (fetomaternal bleeding, FMB) after laser surgery for twin-twin transfusion
      syndrome (TTTS). STUDY DESIGN: A retrospective study of Rhesus-D negative
      patients that underwent laser surgery for TTTS. Patients with and without
      postoperative detectable fetal RBCs on Kleihauer-Betke (KB) testing were compared
      to determine risk factors for FMB. Patients were further sub-classified into
      those with a FMB < 20% and >=20% of estimated fetoplacental blood volume.
      RESULTS: Of 60 studied patients, 26/60 (43%) had a positive postoperative KB
      test. The median fetal:adult RBC ratio was 0.00125, estimated to be a FMB volume
      of 6.25 mL. There were 17/26 (65%) of patients with FMB < 20% and 9/26 (35%)
      patients with >=20% of the fetoplacental blood volume. Stage III-Recipient and
      III-Recipient/Donor patients were more likely to have a positive KB test (14/21
      [66.7%] vs 12/39 [30.8%], OR = 4.50 [1.27-16.54], P = 0.0162). No other risk
      factors for FMB were apparent. CONCLUSIONS: Fetomaternal bleed appears to be a
      common finding after laser surgery for TTTS. TTTS Stage, particularly stage III
      Recipient and III-Recipient/Donor, appears to be a risk factor for FMB.

PMID- 29071723
TI  - Immediate cortical adaptation in visual and non-visual areas functions induced by
      monovision.
AB  - KEY POINTS: Monovision is an optical correction for presbyopes that consists of
      correcting one eye for far distance and the other for near distance, creating a
      superimposition of an in-focus with a blurred image. Brain adaptation to
      monovision was studied in unexperienced observers by measuring visual evoked
      potentials from 64-channels. The first clear effect of monovision on visual
      evoked potentials was the C1 amplitude reduction, indicating that the unilateral
      blurring induced by monovision reduces feed-forward activity in primary visual
      area. Monovision led also to an increased amplitude of the P1 and pP1 components,
      with the latter originating in prefrontal regions. This effect probably works as
      an attentional compensatory activity used to compensate for the degraded V1
      signal. ABSTRACT: A common and often successful option to correct presbyopia with
      contact lenses is monovision. This is an unbalanced correction across the two
      eyes where one eye is corrected for far vision and the other eye is corrected for
      near vision. Monovision is therefore a form of acquired anisometropia that causes
      a superimposition of an in-focus image with a blurred image. In spite of this
      visual anisometropia, monovision has been successfully used for many decadesl
      however the brain mechanism supporting monovision is not well understood. The
      present study aimed to measure the visual evoked potentials with a high-density
      electrode array (64-channel) in a group of presbyopes and to provide a detailed
      spatiotemporal analysis of the cortical activity after a short period of
      adaptation to monovision with contact lenses. When compared with a balanced eye
      near correction, monovision produced both a clear reduction of the earliest
      visual evoked potential components, the C1 and the N1, and an amplitude increase
      of the P1 and pP1. These results indicate that the unilateral blurring induced by
      wearing monovision contact lenses reduces feed-forward activity in the primary
      visual area and feedback activity in extrastriate areas (C1 and N1 reduction).
      Interestingly, other brain activities in both extrastriate visual areas (the P1
      component) and in the anterior insula (the pP1 component) appear to compensate
      for this dysfunction, increasing their activity during monovision. These changes
      confirm the presence of fluid brain adaptation in visual and non-visual areas
      during monocular interferences.

PMID- 29071725
TI  - Ups and downs of calcium in the heart.
AB  - Contraction and relaxation of the heart result from cyclical changes of
      intracellular Ca2+ concentration ([Ca2+ ]i ). The entry of Ca2+ into the cell via
      the L-type Ca2+ current leads to the release of more from the sarcoplasmic
      reticulum (SR). Compared to other regulatory mechanisms such as phosphorylation,
      Ca2+ signalling is very rapid. However, since Ca2+ cannot be destroyed, Ca2+
      signalling can only be controlled by pumping across membranes. In the steady
      state, on each beat, the amount of Ca2+ released from the SR must equal that
      taken back and influx and efflux across the sarcolemma must be equal. Any
      imbalance in these fluxes will result in a change of SR Ca2+ content and this
      provides a mechanism for regulation of SR Ca2+ content. These flux balance
      considerations also explain why simply potentiating Ca2+ release from the SR has
      no maintained effect on the amplitude of the Ca2+ transient. A low diastolic
      [Ca2+ ]i is essential for cardiac relaxation, but the factors that control
      diastolic [Ca2+ ]i are poorly understood. Recent work suggests that flux balance
      is also important here. In particular, decreasing SR function decreases the
      amplitude of the systolic Ca2+ transient and the resulting decrease of Ca2+
      efflux results in an increase of diastolic [Ca2+ ]i to maintain total efflux.

PMID- 29071727
TI  - Transcribed Junk Remains Junk If It Does Not Acquire A Selected Function in
      Evolution.

PMID- 29071726
TI  - International Forum on GMP-grade human platelet lysate for cell propagation.

PMID- 29071729
TI  - Melanoma or pseudo-melanoma? Change in a pigmented lesion after application of
      topical 5-Fluorouracil.

PMID- 29071728
TI  - Impaired excitation-contraction coupling in muscle fibres from the dynamin2R465W
      mouse model of centronuclear myopathy.
AB  - KEY POINTS: Dynamin 2 is a ubiquitously expressed protein involved in membrane
      trafficking processes. Mutations in the gene encoding dynamin 2 are responsible
      for a congenital myopathy associated with centrally located nuclei in the muscle
      fibres. Using muscle fibres from a mouse model of the most common mutation
      responsible for this disease in humans, we tested whether altered Ca2+ signalling
      and excitation-contraction coupling contribute to muscle weakness. The plasma
      membrane network that carries the electrical excitation is moderately perturbed
      in the diseased muscle fibres. The excitation-activated Ca2+ input fluxes across
      both the plasma membrane and the membrane of the sarcoplasmic reticulum are
      defective in the diseased fibres, which probably contributes to muscle weakness
      in patients. ABSTRACT: Mutations in the gene encoding dynamin 2 (DNM2) are
      responsible for autosomal dominant centronuclear myopathy (AD-CNM). We studied
      the functional properties of Ca2+ signalling and excitation-contraction (EC)
      coupling in muscle fibres isolated from a knock-in (KI) mouse model of the
      disease, using confocal imaging and the voltage clamp technique. The transverse
      tubule network organization appeared to be unaltered in the diseased fibres,
      although its density was reduced by ~10% compared to that in control fibres. The
      density of Ca2+ current through CaV1.1 channels and the rate of voltage-activated
      sarcoplasmic reticulum Ca2+ release were reduced by ~60% and 30%, respectively,
      in KI vs. control fibres. In addition, Ca2+ release in the KI fibres reached its
      peak value 10-50 ms later than in control ones. Activation of Ca2+ transients
      along the longitudinal axis of the fibres was more heterogeneous in the KI than
      in the control fibres, with the difference being exacerbated at intermediate
      membrane voltages. KI fibres exhibited spontaneous Ca2+ release events that were
      almost absent from control fibres. Overall, the results of the present study
      demonstrate that Ca2+ signalling and EC coupling exhibit a number of dysfunctions
      likely contributing to muscle weakness in DNM2-related AD-CNM.

PMID- 29071731
TI  - Telemedicine and the senses: a review.
AB  - Telemedicine technologies have been presented as solutions to the challenges of
      equitable, cost-effective and efficient health service provision for over two
      decades. The ways in which the sensory dimensions of medical care and the doctor
      patient relationship are mediated via telemedicine can be important contributors
      to the success, failure or unintended consequences of telemedicine. In this
      article, we present a review of the relevant literature in social research that
      provides insights into the sensory dimensions of telemedicine. In addition to
      considering important relevant work undertaken in the sociology of health and
      illness, we incorporate perspectives and research from other disciplines and
      fields that we believe can contribute to the development of scholarship on this
      topic. We contend that when doctors, patients and other healthcare workers enact
      telemedicine, sensory judgements have become, in part, a sensing of sensors.
      Viewing healthcare practitioners and patients as always and already digital data
      assemblages of flesh-code-space-place-affect-senses, demanding certain kinds of
      body work and data sense-making, constitutes a productive theoretical approach
      for future enquiries into telemedicine and other digital health technologies.

PMID- 29071730
TI  - Transforming growth factor-beta enhances Rho-kinase activity and contraction in
      airway smooth muscle via the nucleotide exchange factor ARHGEF1.
AB  - KEY POINTS: Transforming growth-factor-beta (TGF-beta) and RhoA/Rho-kinase are
      independently implicated in the airway hyper-responsiveness associated with
      asthma, but how these proteins interact is not fully understood. We examined the
      effects of pre-treatment with TGF-beta on expression and activity of RhoA, Rho
      kinase and ARHGEF1, an activator of RhoA, as well as on bradykinin-induced
      contraction, in airway smooth muscle. TGF-beta enhanced bradykinin-induced RhoA
      translocation, Rho-kinase-dependent phosphorylation and contraction, but
      partially suppressed bradykinin-induced RhoA activity (RhoA-GTP content). TGF
      beta enhanced the expression of ARHGEF1, while a small interfering RNA against
      ARHGEF1 and a RhoGEF inhibitor prevented the effects of TGF-beta on RhoA and Rho
      kinase activity and contraction, respectively. ARHGEF1 expression was also
      enhanced in airway smooth muscle from asthmatic patients and ovalbumin-sensitized
      mice. ARHGEF1 is a key TGF-beta target gene, an important regulator of Rho-kinase
      activity and therefore a potential therapeutic target for the treatment of
      asthmatic airway hyper-responsiveness. ABSTRACT: Transforming growth factor-beta
      (TGF-beta), RhoA/Rho-kinase and Src-family kinases (SrcFK) have independently
      been implicated in airway hyper-responsiveness, but how they interact to regulate
      airway smooth muscle contractility is not fully understood. We found that TGF
      beta pre-treatment enhanced acute contractile responses to bradykinin (BK) in
      isolated rat bronchioles, and inhibitors of RhoGEFs (Y16) and Rho-kinase
      (Y27632), but not the SrcFK inhibitor PP2, prevented this enhancement. In
      cultured human airway smooth muscle cells (hASMCs), TGF-beta pre-treatment
      enhanced the protein expression of the Rho guanine nucleotide exchange factor
      ARHGEF1, MLC20 , MYPT-1 and the actin-severing protein cofilin, but not of RhoA,
      ROCK2 or c-Src. In hASMCs, acute treatment with BK triggered subcellular
      translocation of ARHGEF1 and RhoA and enhanced auto-phosphorylation of SrcFK and
      phosphorylation of MYPT1 and MLC20 , but induced de-phosphorylation of cofilin.
      TGF-beta pre-treatment amplified the effects of BK on RhoA translocation and
      MYPT1/MLC20 phosphorylation, but suppressed the effects of BK on RhoA-GTP
      content, SrcFK auto-phosphorylation and cofilin de-phosphorylation. In hASMCs, an
      ARHGEF1 small interfering RNA suppressed the effects of BK and TGF-beta on RhoA
      GTP content, RhoA translocation and MYPT1 and MLC20 phosphorylation, but
      minimally influenced the effects of TGF-beta on cofilin expression and
      phosphorylation. ARHGEF1 expression was also enhanced in ASMCs of asthmatic
      patients and in lungs of ovalbumin-sensitized mice. Our data indicate that TGF
      beta enhances BK-induced contraction, RhoA translocation and Rho-kinase activity
      in airway smooth muscle largely via ARHGEF1, but independently of SrcFK and total
      RhoA-GTP content. A role for smooth muscle ARHGEF1 in asthmatic airway hyper
      responsiveness is worthy of further investigation.

PMID- 29071732
TI  - Unforgiveness: Refining theory and measurement of an understudied construct.
AB  - This research presents a multidimensional conceptualization of unforgiveness and
      the development and validation of the unforgiveness measure (UFM). The scale was
      developed based on a qualitative study of people's experiences of unforgiven
      interpersonal offences (Study 1). Three dimensions of unforgiveness emerged
      (Study 2): emotional-ruminative unforgiveness, cognitive-evaluative
      unforgiveness, and offender reconstrual. We supported the scale's factor
      structure, reliability, and validity (Study 3). We also established the
      convergent and discriminant validity of the UFM with measures of negative affect,
      rumination, forgiveness, cognitive reappraisal, and emotional suppression (Study
      4). Together, our results suggest that the UFM can capture variability in
      victims' unforgiving experiences in the aftermath of interpersonal
      transgressions. Implications for understanding the construct of unforgiveness and
      directions for future research are discussed.

PMID- 29071733
TI  - Two-stage orthogonality based estimation for semiparametric varying-coefficient
      models and its applications in analyzing AIDS data.
AB  - Semiparametric smoothing methods are usually used to model longitudinal data, and
      the interest is to improve efficiency for regression coefficients. This paper is
      concerned with the estimation in semiparametric varying-coefficient models
      (SVCMs) for longitudinal data. By the orthogonal projection method, local linear
      technique, quasi-score estimation, and quasi-maximum likelihood estimation, we
      propose a two-stage orthogonality-based method to estimate parameter vector,
      coefficient function vector, and covariance function. The developed procedures
      can be implemented separately and the resulting estimators do not affect each
      other. Under some mild conditions, asymptotic properties of the resulting
      estimators are established explicitly. In particular, the asymptotic behavior of
      the estimator of coefficient function vector at the boundaries is examined.
      Further, the finite sample performance of the proposed procedures is assessed by
      Monte Carlo simulation experiments. Finally, the proposed methodology is
      illustrated with an analysis of an acquired immune deficiency syndrome (AIDS)
      dataset.

PMID- 29071734
TI  - Nitric oxide is required for the insulin sensitizing effects of contraction in
      mouse skeletal muscle.
AB  - KEY POINTS: People with insulin resistance or type 2 diabetes can substantially
      increase their skeletal muscle glucose uptake during exercise and insulin
      sensitivity after exercise. Skeletal muscle nitric oxide (NO) is important for
      glucose uptake during exercise, although how prior exercise increases insulin
      sensitivity is unclear. In the present study, we examined whether NO is necessary
      for normal increases in skeletal muscle insulin sensitivity after contraction ex
      vivo in mouse muscle. The present study uncovers, for the first time, a novel
      role for NO in the insulin sensitizing effects of ex vivo contraction, which is
      independent of blood flow. ABSTRACT: The factors regulating the increase in
      skeletal muscle insulin sensitivity after exercise are unclear. We examined
      whether nitric oxide (NO) is required for the increase in insulin sensitivity
      after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted
      for 10 min or remained at rest (basal) with or without the NO synthase (NOS)
      inhibition (NG -monomethyl-l-arginine; l-NMMA; 100 MUm). Then, 3.5 h post
      contraction/basal, muscles were exposed to saline or insulin (120 MUU ml-1 ) with
      or without l-NMMA during the last 30 min. l-NMMA had no effect on basal skeletal
      muscle glucose uptake. The increase in muscle glucose uptake with insulin (57%)
      was significantly (P < 0.05) greater after prior contraction (140% increase). NOS
      inhibition during the contractions had no effect on this insulin-sensitizing
      effect of contraction, whereas NOS inhibition during insulin prevented the
      increase in skeletal muscle insulin sensitivity post-contraction. Soluble
      guanylate cyclase inhibition, protein kinase G (PKG) inhibition or cyclic
      nucleotide phosphodiesterase inhibition each had no effect on the insulin
      sensitizing effect of prior contraction. In conclusion, NO is required for
      increases in insulin sensitivity several hours after contraction of mouse
      skeletal muscle via a cGMP/PKG independent pathway.

PMID- 29071736
TI  - Histopathological comparison of healing after maxillary sinus augmentation using
      xenograft mixed with autogenous bone versus allograft mixed with autogenous bone.
AB  - OBJECTIVE: To compare the clinical and histologic outcomes of two different
      grafting materials (allograft and xenograft) when combined with autogenous bone
      and covered with a collagen membrane for sinus augmentation. MATERIAL AND
      METHODS: A parallel case series of fourteen patients in need of a unilateral
      sinus augmentation was evaluated in this study. Seven patients received a graft
      composed by autologous cortical bone (ACB) and anorganic bovine bone in a ratio
      of 1:1; the other seven patients received ACB mixed with an allograft in the same
      ratio. Bone biopsies were obtained 6 months after sinus augmentation at the time
      of implant placement. Comparative histomorphometrical, histopathological, and
      immunohistochemical analyses were conducted and statistically analyzed. RESULTS:
      After 12 months of functional loading, all implants in both groups were clinical
      and radiographically successful. Histomorphometrically, although the initial bone
      formation was not significantly different between groups (new mineralized tissue:
      41.03(12.87)% vs. 34.50(13.18)%, p = .620; allograft vs. xenograft groups), the
      graft resorbed faster in the allograft group (remnant graft particles:
      9.83[7.77]% vs. 21.71[17.88]%; p = .026; allograft vs. xenograft groups). Non
      mineralized tissue did not statistically differ either (49.00[14.32]% vs.
      43.79[19.90]%; p = .710; allograft vs. xenograft groups). The histologic analyses
      revealed higher cellular content, four times more osteoid lines, and higher
      vascularization in the xenograft group. Musashi-1 (mesenchymal stromal cell
      marker) was also more intensively expressed in the xenograft group (p = .019).
      CONCLUSIONS: Both composite grafts generate adequate substratum to receive dental
      implants after healing. Compared with the xenograft composite, allograft
      composite shows faster turnover and a quicker decrease in biological action after
      6 months.

PMID- 29071735
TI  - Impact of sample collection participation on the validity of estimated measures
      of association in the National Birth Defects Prevention Study when assessing gene
      environment interactions.
AB  - To better understand the impact that nonresponse for specimen collection has on
      the validity of estimates of association, we examined associations between self
      reported maternal periconceptional smoking, folic acid use, or pregestational
      diabetes mellitus and six birth defects among families who did and did not submit
      buccal cell samples for DNA following a telephone interview as part of the
      National Birth Defects Prevention Study (NBDPS). Analyses included control
      families with live born infants who had no birth defects (N = 9,465), families of
      infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N =
      1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial
      clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of
      delivery were between 1997 and 2009. For each exposure and birth defect, odds
      ratios and 95% confidence intervals were calculated using logistic regression
      stratified by race-ethnicity and sample collection status. Tests for interaction
      were applied to identify potential differences between estimated measures of
      association based on sample collection status. Significant differences in
      estimated measures of association were observed in only four of 48 analyses with
      sufficient sample sizes. Despite lower than desired participation rates in buccal
      cell sample collection, this validation provides some reassurance that the
      estimates obtained for sample collectors and noncollectors are comparable. These
      findings support the validity of observed associations in gene-environment
      interaction studies for the selected exposures and birth defects among NBDPS
      participants who submitted DNA samples.

PMID- 29071737
TI  - On the testing of Hardy-Weinberg proportions and equality of allele frequencies
      in males and females at biallelic genetic markers.
AB  - Standard statistical tests for equality of allele frequencies in males and
      females and tests for Hardy-Weinberg equilibrium are tightly linked by their
      assumptions. Tests for equality of allele frequencies assume Hardy-Weinberg
      equilibrium, whereas the usual chi-square or exact test for Hardy-Weinberg
      equilibrium assume equality of allele frequencies in the sexes. In this paper, we
      propose ways to break this interdependence in assumptions of the two tests by
      proposing an omnibus exact test that can test both hypotheses jointly, as well as
      a likelihood ratio approach that permits these phenomena to be tested both
      jointly and separately. The tests are illustrated with data from the 1000 Genomes
      project.

PMID- 29071739
TI  - Recent Applications of 2D Inorganic Nanosheets for Emerging Energy Storage
      System.
AB  - Among many types of nanostructured inorganic materials, highly anisotropic 2D
      nanosheets provide unique advantages in designing and synthesizing efficient
      electrode and electrocatalyst materials for novel energy storage technologies. 2D
      inorganic nanosheets boast lots of unique characteristics such as high surface
      area, short ion diffusion path, tailorable compositions, and tunable electronic
      structures. These merits of 2D inorganic nanosheets render them promising
      candidate materials as electrodes for diverse secondary batteries and
      supercapacitors, and electrocatalysts. A wide spectrum of examples is presented
      for inorganic nanosheet-based electrodes and electrocatalysts. Future
      perspectives in research about 2D nanosheet-based functional materials are
      discussed to provide insight for the development of next-generation energy
      storage systems using 2D nanostructured materials.

PMID- 29071740
TI  - Coaptation Triangle and Golden Proportion in mitral valve anatomy. Does nature
      play with geometry?
AB  - INTRODUCTION: The Coaptation Triangle, or Tenting Area, can be identified on long
      axis 2D images. Its assessment is a routine practice during echocardiographic
      mitral evaluation. The Golden Proportion is a particular geometric ratio between
      two segments. Its value is an irrational number, commonly rounded to 0.618 and
      showing unique geometrical/mathematical properties. Interestingly, its presence
      has been documented in an extremely variable number of natural settings.
      Hypothesizing the presence of the Golden Proportion in normal mitral anatomy, we
      examined the Coaptation Triangle of healthy valves to investigate such a theory.
      METHODS AND RESULTS: A total of 41 healthy adults, with normal mitral valves,
      underwent 2D echocardiography. Adequate images were chosen and loaded into custom
      software. Firstly, the Coaptation Triangle was manually drawn by the operator.
      Then, a second Coaptation Triangle, with the same base, but based on Golden
      Proportion, was automatically built by the software. Eventually, the two
      triangles were analyzed and compared. All retrieved measurements were
      investigated for differences and correlations. Ratios close to the Golden
      Proportion were found in several locations of the manually drawn Coaptation
      Triangle. On the other hand, comparing the manually drawn Coaptation Triangle
      with the automatically built one, no significant differences were revealed, and
      very strong correlations were demonstrated. CONCLUSION: The Golden Proportion
      appears present in the geometry of normal mitral valves. Studying such an aspect
      and identifying disruption in anatomical proportions could improve early
      diagnosis of mitral alterations, and allows a more standardized follow-up and
      help surgeons to plan a repair strategy, particularly quantifying the needed
      surgical modifications.

PMID- 29071738
TI  - Assessment of contact predictions in CASP12: Co-evolution and deep learning
      coming of age.
AB  - Following up on the encouraging results of residue-residue contact prediction in
      the CASP11 experiment, we present the analysis of predictions submitted for
      CASP12. The submissions include predictions of 34 groups for 38 domains
      classified as free modeling targets which are not accessible to homology-based
      modeling due to a lack of structural templates. CASP11 saw a rise of coevolution
      based methods outperforming other approaches. The improvement of these methods
      coupled to machine learning and sequence database growth are most likely the main
      driver for a significant improvement in average precision from 27% in CASP11 to
      47% in CASP12. In more than half of the targets, especially those with many
      homologous sequences accessible, precisions above 90% were achieved with the best
      predictors reaching a precision of 100% in some cases. We furthermore tested the
      impact of using these contacts as restraints in ab initio modeling of 14 single
      domain free modeling targets using Rosetta. Adding contacts to the Rosetta
      calculations resulted in improvements of up to 26% in GDT_TS within the top five
      structures.

PMID- 29071741
TI  - Is right atrioventricular valve always tricuspid?
AB  - A 71-year-old male with a medical history of hypertension was admitted to
      emergency department with hypertensive pulmonary edema. The patient appeared
      anxious and diaphoretic, and physical examination revealed tachypnea, crepitant
      rales in the both lungs and a systolic ejection murmur at the right sternal
      border, radiating to the both carotid arteries. The electrocardiography showed
      sinus tachycardia with indications of left ventricle hypertrophy Before the
      aortic valve surgery, transesophageal echocardiography (TEE) was performed for
      detailed evaluation of the aortic valve. Two-dimensional TEE showed mild
      tricuspid valve regurgitation and only two of three leaflets of the tricuspid
      valve at a time.

PMID- 29071742
TI  - Assessment of protein assembly prediction in CASP12.
AB  - We present the results of the first independent assessment of protein assemblies
      in CASP. A total of 1624 oligomeric models were submitted by 108 predictor groups
      for the 30 oligomeric targets in the CASP12 edition. We evaluated the accuracy of
      oligomeric predictions by comparison to their reference structures at the
      interface patch and residue contact levels. We find that interface patches are
      more reliably predicted than the specific residue contacts. Whereas none of the
      15 hard oligomeric targets have successful predictions for the residue contacts
      at the interface, six have models with resemblance in the interface patch.
      Successful predictions of interface patch and contacts exist for all targets
      suitable for homology modeling, with at least one group improving over the best
      available template for each target. However, the participation in protein
      assembly prediction is low and uneven. Three human groups are closely ranked at
      the top by overall performance, but a server outperforms all other predictors for
      targets suitable for homology modeling. The state of the art of protein assembly
      prediction methods is in development and has apparent room for improvement,
      especially for assemblies without templates.

PMID- 29071743
TI  - [Co2 @Ge16 ]4- : Localized versus Delocalized Bonding in Two Isomeric
      Intermetalloid Clusters.
AB  - We report the successful isolation and structural elucidation of two bimetallic
      doped [Co2 @Ge16 ]4- clusters (alpha and beta form), which were synthesized
      through the reaction of [{(ArN)2 CtBu}Co(eta6 -toluene)] (Ar=2,6
      diisopropylphenyl) and K4 Ge9 in ethylenediamine (en) solution and co
      crystallized together in [K(2,2,2-crypt)]4 [Co2 @Ge16 ]?en. The alpha-[Co2 @Ge16
      ]4- isomer prefers a distinct D2h 3-connected architecture, whereas the
      deltahedral isomeric beta-[Co2 @Ge16 ]4- isomer adopts a quasi-C2h geometry and
      can be seen as coupling of two distorted arachno-[Co@Ge10 ] units. Chemical
      bonding analyses indicate that the skeleton of the alpha isomer is mainly
      composed of localized bonds, whereas only multicenter bonding interactions govern
      the geometry of the beta isomer, which was further found to exhibit a fluxional
      behavior. The coexistence of both isomers within one unit cell links the 3
      connected clusters with their deltahedral congeners, thus highlighting the
      structural and electronic flexibility of such discreet cluster systems.

PMID- 29071744
TI  - Chemistry of Graphene Derivatives: Synthesis, Applications, and Perspectives.
AB  - The chemistry of graphene and its derivatives is one of the hottest topics of
      current material science research. The derivatisation of graphene is based on
      various approaches, and to date functionalization with halogens, hydrogen,
      various functional groups containing oxygen, sulfur, nitrogen, phosphorus, boron,
      and several other elements have been reported. Most of these functionalizations
      are based on sp3 hybridization of carbon atoms in the graphene skeleton, which
      means the formation of out-of-plane covalent bonds. Several elements were also
      reported for substitutional modification of graphene, where the carbon atoms are
      substituted with atoms like nitrogen, boron, and several others. From tens of
      functional groups, for only two of them were reported full functionalization of
      graphene skeleton and formation of its stoichiometric counterparts,
      fluorographene and hydrogenated graphene. The functionalization of graphene is
      crucial for most of its applications including energy storage and conversion
      devices, electronic and optic applications, composites, and many others.

PMID- 29071745
TI  - Anterior mitral valve perforation in the absence of acute infection: Diagnosis by
      two-dimensional and three-dimensional transesophageal echocardiography.
AB  - Anterior mitral valve leaflet (AMVL) perforation is most commonly seen in the
      setting of infective endocarditis. We present a case of AMVL perforation in a
      previously healthy 62-year-old male who presented with a six-month history of
      worsening dyspnea and peripheral edema. Blood cultures, inflammatory markers, and
      autoimmune profile were negative. Transthoracic echocardiography demonstrated
      severe mitral regurgitation (MR) with a possible AMVL perforation, which was
      confirmed by three-dimensional transesophageal echocardiography as a well
      circumscribed hole in the A2 segment. The patient made a successful recovery from
      mitral valve repair surgery.

PMID- 29071746
TI  - Spontaneous embolization of an atrial septal defect occluder device into the left
      ventricular outflow tract in a patient with pulmonary stenosis.
AB  - A 24-year-old man was admitted to our outpatient clinic for his routine checkup
      of consecutively percutaneously treated atrial septal defect (ASD) and pulmonary
      valvular stenosis 45 days ago. A 24 mm ASD occluder device was implanted under
      transthoracic echocardiographic guidance and 80 mm Hg peak-to-peak pulmonary
      valvular gradient decreased to 20 mm Hg gradient after pulmonary valve dilatation
      with 23 mm NUMED II transluminal valvuloplasty catheter balloon. Atrial septal
      defect (ASD) closure is now routinely performed using a percutaneous approach
      under echocardiographic guidance especially transthoracic echocardiography (TEE).
      Centrally located, ostium secundum type and less than 3.5 cm in size are
      considered ideal for device closure. Although there is considerable variation in
      size and location of the defects, TEE guidance is quite important for this
      proportion of ASDs. The selection of patients for percutaneous transcatheter
      closure of a secundum ASD requires accurate information regarding the anatomy of
      the defect such as its maximal diameter and the amount of circumferential tissue
      rims.

PMID- 29071748
TI  - Challenges and opportunities for transboundary conservation of migratory birds in
      the East Asian-Australasian flyway.

PMID- 29071747
TI  - The management of anticoagulation in patients undergoing therapeutic plasma
      exchange: A concise review.
AB  - We surveyed multiple apheresis centers represented by the authors for their
      clinical approach to the management of anticoagulation issues during therapeutic
      plasma exchange (TPE). We present the results of their practices and a review of
      the pertinent literature. As plasma is removed during TPE, replacement with all
      or partial non-plasma-containing fluids (eg, 5% albumin) may lead to significant
      changes in hemostasis. These changes are amplified in patients who are receiving
      anticoagulation. We discuss various anticoagulants as well as the monitoring and
      adjustment of anticoagulation before, during, and after TPE. No single guideline
      can be applied, but rather, patients must be monitored individually, taking into
      account their often complex clinical conditions and medication profiles.

PMID- 29071749
TI  - Abnormal drainage of inferior vena cava to left atrium together with a partial
      abnormal pulmonary venous drainage to right atrium in the presence of atrial
      septal defect.
AB  - The direct abnormal drainage of the inferior vena cava (IVC), while rare, is well
      recognized anomaly of systemic venous drainage. It has been reported both in
      isolation and in association with other cardiac defects. This is a case of an
      abnormal drainage of IVC into left atrium (LA) together with partial abnormal
      pulmonary venous drainage to the right atrium (RA) and atrium septal defect
      (ASD).

PMID- 29071750
TI  - Assessment of the model refinement category in CASP12.
AB  - We here report on the assessment of the model refinement predictions submitted to
      the 12th Experiment on the Critical Assessment of Protein Structure Prediction
      (CASP12). This is the fifth refinement experiment since CASP8 (2008) and, as with
      the previous experiments, the predictors were invited to refine selected server
      models received in the regular (nonrefinement) stage of the CASP experiment. We
      assessed the submitted models using a combination of standard CASP measures. The
      coefficients for the linear combination of Z-scores (the CASP12 score) have been
      obtained by a machine learning algorithm trained on the results of visual
      inspection. We identified eight groups that improve both the backbone
      conformation and the side chain positioning for the majority of targets. Albeit
      the top methods adopted distinctively different approaches, their overall
      performance was almost indistinguishable, with each of them excelling in
      different scores or target subsets. What is more, there were a few novel
      approaches that, while doing worse than average in most cases, provided the best
      refinements for a few targets, showing significant latitude for further
      innovation in the field.

PMID- 29071751
TI  - PXR mediated induction of CYP3A4, CYP1A2, and P-gp by Mitragyna speciosa and its
      alkaloids.
AB  - Kratom (Mitragyna speciosa), a native herb of Southeast Asia, is widely known for
      its psychoactive properties. Recent increase in the use of kratom as a
      recreational drug has increased the risk of its interaction with conventional
      drugs if taken concomitantly. A few reports are available related to the effects
      of kratom on the activity of cytochrome P450 enzymes (CYPs), but there are no
      reports of its effects on pregnane X receptor (PXR), a transcription factor that
      regulates the expression of CYPs and P-glycoprotein (P-gp). This study was
      carried out to evaluate the effects of a methanolic extract of kratom leaves, an
      alkaloid rich fraction and its 5 indole and 4 oxindole alkaloids on PXR
      activation and the resulting changes in the mRNA expression of PXR target genes
      (CYP3A4, CYP1A2, and P-gp). A significant activation of PXR was observed by the
      extract (3-fold), alkaloidal fraction (4-fold) and all 9 alkaloids (4- to 6-fold)
      that was associated with an increased mRNA expression which resulted into an
      increase in the activity of CYP3A4, CYP1A2, and P-gp. These results indicate that
      high consumption of Mitragyna speciosa extract along with the conventional drugs
      may lead to potential herb-drug interactions due to its effects on PXR.

PMID- 29071752
TI  - One-Step Synthesis of B/N Co-doped Graphene as Highly Efficient Electrocatalyst
      for the Oxygen Reduction Reaction: Synergistic Effect of Impurities.
AB  - In the last decade, numerous studies of graphene doping by various metal and
      nonmetal elements have been done in order to obtain tailored properties, such as
      non-zero band gap, electrocatalytic activity, or controlled optical properties.
      From nonmetal elements, boron and nitrogen were the most studied dopants.
      Recently, it has been shown that in some cases the enhanced electrocatalytic
      activity of graphene and its derivatives can be attributed to metal impurities
      rather than to nonmetal elements. In this paper, we investigated the
      electrocatalytical properties of B/N co-doped graphene with respect to the
      content of metallic impurities introduced by the synthesis procedures. For this
      purpose, a permanganate (Hummers) and a chlorate (Hofmann) route were used for
      the preparation of the starting graphene oxides (GO). The GO used for the
      synthesis of B/N co-doped graphene had significantly difference compositions of
      oxygen functionalities as well as metallic impurities introduced by the different
      synthetic procedures. We performed a detailed structural and chemical analysis of
      the doped graphene samples to correlate their electrocatalytic activity with the
      concentration of incorporated boron and nitrogen as well as metallic impurities.

PMID- 29071754
TI  - C-H Insertions by Iron Porphyrin Carbene: Basic Mechanism and Origin of Substrate
      Selectivity.
AB  - Recent experimental reports of heme carbene C-H insertions show promising results
      for sustainable chemistry due to good yield and selectivity, low cost of iron,
      and low/no toxicity of hemes. But mechanistic details are mostly unknown. Despite
      structural similarity and isoelectronic nature between heme carbene and the FeIV
      =O intermediate, our quantum chemical studies with detailed geometric and
      electronic information for the first time reveal an FeII -based, concerted,
      hydride-transfer mechanism, which is different from the FeIV -based stepwise
      hydrogen atom transfer mechanism for C-H functionalization by native heme
      enzymes. A trend of broad range experimental C-H insertion yields (0-88 %) of
      five different C-H bonds, including mostly non-functionalized moieties, was well
      reproduced. Results suggest that the substrate selectivity originates from the
      hydride formation capability. The predicted kinetic isotope effects were also in
      excellent agreement with experiment. Useful geometry, charge, and energy
      parameters well correlated with barriers were reported. These results provide the
      first theoretical evidence that carbene formation is the overall rate-limiting
      step, and suggest a key role of the formation of strong electrophilic heme
      carbene in developing heme-based C-H insertion catalysts and biocatalysts.

PMID- 29071753
TI  - DNA Hydrogel with Tunable pH-Responsive Properties Produced by Rolling Circle
      Amplification.
AB  - Recently, smart DNA hydrogels, which are generally formed by the self-assembly of
      oligonucleotides or through the cross-linking of oligonucleotide-polymer hybrids,
      have attracted tremendous attention. However, the difficulties of fabricating DNA
      hydrogels limit their practical applications. We report herein a novel method for
      producing pH-responsive hydrogels by rolling circle amplification (RCA). In this
      method, pH-sensitive cross-linking sites were introduced into the polymeric DNA
      chains during DNA synthesis. As the DNA sequence can be precisely defined by its
      template, the properties of such hydrogels can be finely tuned in a very facile
      way through template design. We have investigated the process of hydrogel
      formation and pH-responsiveness to provide rationales for functional hydrogel
      design based on the RCA reaction.

PMID- 29071755
TI  - Effect of aromatherapy massage on anxiety, depression, and physiologic parameters
      in older patients with the acute coronary syndrome: A randomized clinical trial.
AB  - PURPOSE: This study aimed to investigate the effect of aromatherapy massage on
      anxiety, depression, and physiologic parameters in older patients with acute
      coronary syndrome. METHODS: This randomized controlled trial was conducted on 90
      older women with acute coronary syndrome. The participants were randomly assigned
      into the intervention and control groups (n = 45). The intervention group
      received reflexology with lavender essential oil, but the control group only
      received routine care. Physiologic parameters, the levels of anxiety and
      depression in the hospital were evaluated using a checklist and the Hospital's
      Anxiety and Depression Scale, respectively, before and immediately after the
      intervention. RESULTS: Significant differences in the levels of anxiety and
      depression were reported between the groups after the intervention. The analysis
      of physiological parameters revealed a statistically significant reduction (P <
      .05) in systolic blood pressure, diastolic blood pressure, mean arterial
      pressure, and heart rate. However, no significant difference was observed in the
      respiratory rate. CONCLUSIONS: Aromatherapy massage can be considered by clinical
      nurses an efficient therapy for alleviating psychological and physiological
      responses among older women suffering from acute coronary syndrome.

PMID- 29071756
TI  - Novel electrophysiological criteria for septal ventricular outflow tract
      tachycardias requiring a sequential bilateral ablation.
AB  - BACKGROUND: Septal ventricular outflow tract ventricular arrhythmias (OT-VAs) are
      defined as septal origin VAs from the right ventricular or left ventricular OT.
      Patients with septal OT-VAs may require a sequential bilateral OT ablation. This
      study aimed to evaluate the electrophysiological characteristics and ablation
      outcome in patients with septal OT-VAs. METHODS: We retrospectively analyzed the
      electrocardiography and electrophysiological parameters in 96 patients (mean age
      49 +/- 15 years, 49 male) undergoing bilateral activation mapping before catheter
      ablation of idiopathic septal OT-VAs. The patients were categorized into three
      groups based on the successful ablation sites, including the right ventricular
      outflow tract (RVOT), RVOT/left ventricular outflow tract (LVOT), and LVOT.
      RESULTS: Mapping in the three groups demonstrated a gradually decreasing and
      increasing trend in the earliest activation time obtained from the RVOT and LVOT,
      respectively. The absolute earliest activation time discrepancy (AEAD) of <=18
      milliseconds could predict the requirement for a sequential bilateral ablation
      with a sensitivity and specificity of 100.0% and 93.7%, respectively. The small
      AEAD (<=21 milliseconds) was associated with a higher recurrence rate in patients
      receiving a successful unilateral ablation, while patients with a longer distance
      between the bilateral OT earliest activation sites (DEA > 26 mm) increased future
      recurrences after an initially successful sequential bilateral ablation.
      CONCLUSIONS: The application of bilateral OT-VA activation mapping and the
      measurement of the AEAD and DEA provided not only pivotal information for the
      ablation strategy, but also prognostic implications for recurrences in patients
      with septal OT-VAs.

PMID- 29071757
TI  - Potential cow milk xanthine oxidase inhibitory and antioxidant activity of
      selected phenolic acid derivatives.
AB  - Xanthine oxidase (XO) found in all mammals and excess activity leads to
      urolithiasis. The cow milk XO was purified to 305-fold with a specific activity
      of 8.76 EU/mg and overall yield of 87% by using DEAE-Sepharose chromatography.
      The phenolics showed potent XO inhibitory effect with Ki , P1 (0.412), P2
      (0.632), P3 (0.585), P4 (0.886), P5 (1.633), P6 (0.503), P7 (2.882), P8 (3.761),
      P9 (4.487), and P10 (5.841) MUM. The phenolics P9 and P10 exhibited uncompetitive
      inhibition; the phenolics P1, P2, P3, P4, and P6 showed competitive inhibition,
      and other phenolic acids showed noncompetitive inhibition. The studied phenolic
      compounds showed potent antioxidant activity and expressed as EC50 , ranged from,
      DPPH (4.2-25.8 MUg mL-1 ), ABTS (10.2-42.5 mmol TE 100 g-1 ), and FRAP (6.3-36.8
      mol Fe (II) 100 g-1 ). The results obtained from this study might be utilized for
      design of XO inhibitors and as antigout agent.

PMID- 29071758
TI  - CT versus thoracic ultrasound for discriminating uncomplicated and complicated
      parapneumonic pleural effusions.

PMID- 29071759
TI  - Curiosity-based learning in infants: a neurocomputational approach.
AB  - Infants are curious learners who drive their own cognitive development by
      imposing structure on their learning environment as they explore. Understanding
      the mechanisms by which infants structure their own learning is therefore
      critical to our understanding of development. Here we propose an explicit
      mechanism for intrinsically motivated information selection that maximizes
      learning. We first present a neurocomputational model of infant visual category
      learning, capturing existing empirical data on the role of environmental
      complexity on learning. Next we "set the model free", allowing it to select its
      own stimuli based on a formalization of curiosity and three alternative selection
      mechanisms. We demonstrate that maximal learning emerges when the model is able
      to maximize stimulus novelty relative to its internal states, depending on the
      interaction across learning between the structure of the environment and the
      plasticity in the learner itself. We discuss the implications of this new
      curiosity mechanism for both existing computational models of reinforcement
      learning and for our understanding of this fundamental mechanism in early
      development.

PMID- 29071761
TI  - Combination therapy strategies for improving PD-1 blockade efficacy: a new era in
      cancer immunotherapy.
AB  - Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively
      regulates T-cell immune function through the interaction with its ligand PD-L1.
      Blockage of this interaction unleashes the immune system to fight cancer.
      Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of
      cancer drug discovery, owing to its durable effect against a wide variety of
      cancers with limited adverse effects. A brief history and development of PD-1
      blockade, from the initial discovery of PD-1 to the recent clinical output of
      this therapy, have been summarized here. Despite its tremendous clinical success
      rate over other cancer treatments, PD-1 blockade has its own pitfall; a
      significant fraction of patients remains unresponsive to this therapy. The key to
      improve the PD-1 blockade therapy is the development of combination therapies. As
      this approach has garnered worldwide interest, here, we have summarized the
      recent trends in the development of PD-1 blockade-based combination therapies and
      the ongoing clinical trials. These include combinations with checkpoint
      inhibitors, radiation therapy, chemotherapy and several other existing cancer
      treatments. Importantly, FDA has approved PD-1 blockade agent to be used in
      combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD
      1 blockade therapy is affected by tumour and immune system-related factors. The
      role of the immune system, especially T cells, in determining the responsiveness
      has been poorly studied compared with those factors related to the tumour side.
      Energy metabolism has emerged as one of the important regulatory mechanisms for
      the function and differentiation of T cells. We have documented here the recent
      results regarding the augmentation of PD-1 blockade efficacy by augmenting
      mitochondrial energy metabolism of T cell.

PMID- 29071760
TI  - See and be seen: Infant-caregiver social looking during locomotor free play.
AB  - Face-to-face interaction between infants and their caregivers is a mainstay of
      developmental research. However, common laboratory paradigms for studying dyadic
      interaction oversimplify the act of looking at the partner's face by seating
      infants and caregivers face to face in stationary positions. In less constrained
      conditions when both partners are freely mobile, infants and caregivers must move
      their heads and bodies to look at each other. We hypothesized that face looking
      and mutual gaze for each member of the dyad would decrease with increased motor
      costs of looking. To test this hypothesis, 12-month-old crawling and walking
      infants and their parents wore head-mounted eye trackers to record eye movements
      of each member of the dyad during locomotor free play in a large toy-filled
      playroom. Findings revealed that increased motor costs decreased face looking and
      mutual gaze: Each partner looked less at the other's face when their own posture
      or the other's posture required more motor effort to gain visual access to the
      other's face. Caregivers mirrored infants' posture by spending more time down on
      the ground when infants were prone, perhaps to facilitate face looking. Infants
      looked more at toys than at their caregiver's face, but caregivers looked at
      their infant's face and at toys in equal amounts. Furthermore, infants looked
      less at toys and faces compared to studies that used stationary tasks, suggesting
      that the attentional demands differ in an unconstrained locomotor task. Taken
      together, findings indicate that ever-changing motor constraints affect real-life
      social looking.

PMID- 29071763
TI  - Stress, sex, and plague: Patterns of developmental stress and survival in pre-
      and post-Black Death London.
AB  - OBJECTIVES: Previous research revealed declines in survivorship in London before
      the Black Death (c. 1346-1353), and improvements in survivorship following the
      epidemic. These trends indicate that there were declines in general levels of
      health before the Black Death and improvements thereof afterwards. This study
      expands on previous research by examining whether changes in survivorship were
      consistent between the sexes, and how patterns of developmental stress markers
      changed before and after the Black Death. MATERIALS AND METHODS: This study uses
      samples from London cemeteries dated to one of three periods: Early Pre-Black
      Death (1000-1200 AD, n = 255), Late Pre-Black Death (1200-1250 AD, n = 247), or
      Post-Black Death (1350-1540 AD n = 329). Temporal trends in survivorship are
      assessed via Kaplan-Meier survival analysis, and trends in tibial length (as a
      proxy for stature) and linear enamel hypoplasia (LEH) are assessed using t-tests
      and Chi-square tests, respectively. RESULTS: Survivorship for both sexes
      decreased before the Black Death and increased afterwards. For males, LEH
      frequencies increased and stature decreased before the epidemic, and LEH declined
      and stature increased after the Black Death. For females, the only significant
      change with respect to developmental stress markers was a decrease in stature
      after the Black Death. CONCLUSIONS: These results might reflect variation between
      the sexes in sensitivity to stressors, the effects of nutrition on pubertal
      timing, disproportionate access to dietary resources for males in the aftermath
      of the Black Death, the disproportionate deaths of frail individuals during the
      epidemic, or some combination of these factors.

PMID- 29071762
TI  - Combination of carvacrol with simvastatin improves the lipid-lowering efficacy
      and alleviates simvastatin side effects.
AB  - The present investigation was designed to examine the possible additive
      hypolipidemic effect of carvacrol (CARV) in combination with simvastatin (SIM) on
      poloxamer 407 (P407)-induced hyperlipidemia. Rats were injected with P407, (500
      mg/ kg; i.p.), twice a week, for 30 days. Treatment was carried out by
      administration of SIM (20 mg/kg/day; p.o.) or CARV (50 mg/kg/day; p.o.) or
      combination of them. Treatment with CARV significantly decreased total
      cholesterol, triglycerides, low-density lipoprotein, atherogenic index, leptin,
      and increased high-density lipoprotein and adiponectin. Moreover, CARV
      potentiated the hypolipidemic effect of SIM. Both SIM and CARV alleviated the
      oxidative stress induced by P407. Interestingly, CARV, when combined with SIM,
      significantly ameliorated SIM-induced liver and muscle injury by reducing the
      level of alanine aminotransferase, aspartate aminotransferase, lactate
      dehydrogenase, creatine kinase, and myoglobin and restoring the normal
      histological picture of both liver and muscle as well as apoptosis.

PMID- 29071764
TI  - A randomized controlled pilot trial of vilazodone for adult separation anxiety
      disorder.
AB  - BACKGROUND: Separation anxiety disorder was recently recognized by fifth edition
      of the Diagnostic and Statistical Manual of Mental Disorders as a diagnosis in
      adults, but no publications to date have characterized a sample of patients
      seeking treatment for adult separation anxiety disorder (ASAD) or assessed
      treatment efficacy. We hypothesized that vilazodone, a selective serotonin
      reuptake inhibitor (SSRI) and serotonin 1a (5HT1a ) receptor partial agonist,
      would have efficacy in ASAD, because SSRIs have appeared efficacious in children
      with mixed diagnoses including separation anxiety disorder and in animal models
      of separation anxiety. METHODS: In this pilot study, 24 adults (ages 18-60) with
      a principal diagnosis of ASAD were randomized to 12 weeks of double-blind
      treatment with vilazodone (n = 13) or placebo (n = 11). Outcome was assessed by
      an independent evaluator and self-ratings, and analyzed with mixed effect models.
      RESULTS: This sample was predominantly female (67%), with comorbid psychiatric
      disorders (58%), and adult onset of separation anxiety disorder (62%). Response
      rates at week 12 did not differ significantly between groups. Across all time
      points, the vilazodone group evidenced greater improvement on the Structured
      Clinical Interview for Separation Anxiety Symptoms (P = .026) and the Quality of
      Life Enjoyment and Satisfaction Questionnaire (P = .011), and trends toward
      greater improvement on the Adult Separation Anxiety Questionnaire (P = .054) and
      the Clinical Global Impression-Change Scale (P = .086), all with large between
      group effect sizes. CONCLUSIONS: Findings demonstrate feasibility of a clinical
      trial in ASAD, and they suggest that vilazodone may have efficacy in the
      treatment of ASAD and warrants further study.

PMID- 29071765
TI  - Ablation of paroxysmal atrial fibrillation using a second-generation cryoballoon
      catheter or contact-force sensing radiofrequency ablation catheter: A comparison
      of costs and long-term clinical outcomes.
AB  - INTRODUCTION: Although noninferiority of cryoballoon ablation (CBA) and
      radiofrequency catheter ablation for antral pulmonary vein isolation (APVI) has
      been reported in patients with paroxysmal atrial fibrillation (PAF), it is not
      clear whether contact force sensing (CF-RFA) and CBA with the second-generation
      catheter have similar procedural costs and long-term outcomes. The objective of
      this study is to compare the long-term efficacy and cost implications of CBA and
      CF-RFA in patients with PAF. METHODS AND RESULTS: A first APVI was performed in
      146 consecutive patients (age: 63 +/- 10 years, men: 95 [65%], left atrial
      diameter: 42 +/- 6 mm) with PAF using CBA (71) or CF-RFA (75). Clinical outcomes
      and procedural costs were compared. The mean procedure time was significantly
      shorter with CBA than with CF-RFA (98 +/- 39 vs. 158 +/- 47 minutes, P < 0.0001).
      Despite a higher equipment cost in the CBA than the CF-RFA group, the total
      procedure cost was similar between the two groups (P = 0.26), primarily driven by
      a shorter procedure duration that resulted in a lower anesthesia cost. At 25 +/-
      5 months after a single ablation procedure, 51 patients (72%) in the CBA, and 55
      patients (73%) in the CF-RFA groups remained free from atrial arrhythmias without
      antiarrhythmic drug therapy (P = 0.84). CONCLUSIONS: The procedure duration was
      approximately 60 minutes shorter with CBA than CF-RFA. The procedural costs were
      similar with both approaches. At 2 years after a single procedure, CBA and CF-RFA
      have similar single-procedure efficacies of 72-73%.

PMID- 29071767
TI  - Communicating Value in Simulation: Cost Benefit Analysis and Return on
      Investment.
AB  - Value-based health care requires a balancing of medical outcomes with economic
      value. Administrators need to understand both the clinical and economic effects
      of potentially expensive simulation programs to rationalize the costs. Given the
      often-disparate priorities of clinical educators relative to health care
      administrators, justifying the value of simulation requires the use of economic
      analyses few physicians have been trained to conduct. Clinical educators need to
      be able to present thorough economic analyses demonstrating returns on investment
      and cost effectiveness to effectively communicate with administrators. At the
      2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change
      through Health Care Simulation: Systems, Competency, and Outcomes", our breakout
      session critically evaluated the cost benefit and return on investment of
      simulation. In this paper we provide an overview of some of the economic tools
      that a clinician may use to present the value of simulation training to financial
      officers and other administrators in the economic terms they understand. We also
      define three themes as a call to action for research related to cost benefit
      analysis in simulation as well as four specific research questions that will help
      guide educators and hospital leadership to make decisions on the value of
      simulation for their system or program. This article is protected by copyright.
      All rights reserved.

PMID- 29071766
TI  - Holistic health care: Patients' experiences of health care provided by an
      Advanced Practice Nurse.
AB  - INTRODUCTION: Advanced Practice Nurse (APN) is a fairly new role in the Swedish
      health care system. AIM: To describe patients' experiences of health care
      provided by an APN in primary health care. METHODS: An inductive, descriptive
      qualitative approach with qualitative open-ended interviews was chosen to obtain
      descriptions from 10 participants regarding their experiences of health care
      provided by an APN. The data were collected during the spring 2012, and a
      qualitative approach was used for analyze. RESULTS: The APNs had knowledge and
      skills to provide safe and secure individual and holistic health care with high
      quality, and a respectful and flexible approach. The APNs conveyed trust and
      safety and provided health care that satisfied the patients' needs of
      accessibility and appropriateness in level of care. CONCLUSION: The APNs way of
      providing health care and promoting health seems beneficial in many ways for the
      patients. The individual and holistic approach that characterizes the health care
      provided by the APNs is a key aspect in the prevailing change of health care
      practice. The transfer of care and the increasing number of older adults, often
      with a variety of complex health problems, call for development of the new role
      in this context.

PMID- 29071769
TI  - Inhibition of fatty acid amide hydrolase in the central amygdala alleviates co
      morbid expression of innate anxiety and excessive alcohol intake.
AB  - Fatty acid amide hydrolase (FAAH) is an enzyme that prominently degrades the
      major endocannabinoid N-arachidonoylethanolamine (anandamide). Inhibition of this
      enzyme leads to increased anandamide levels in brain regions that modulate stress
      and anxiety. Recently, we found that genetically selected Marchigian Sardinian
      alcohol-preferring (msP) rats display hyperactive FAAH in amygdalar regions that
      was associated with increased stress sensitivity and a hyper-anxious phenotype.
      Our previous work has also demonstrated that msPs display an innate preference
      for and excessive consumption of alcohol, potentially reflecting a form of self
      medication to gain relief from hyper-anxious states. Here, we expand on our
      previous work by microinjecting the selective FAAH inhibitor URB597 (vehicle,
      0.03, 0.1 and 1.0 MUg per rat) into the central amygdala (CeA) and basolateral
      amygdala in msP versus non-selected Wistar rats to evaluate the effects of
      localized FAAH inhibition on operant alcohol self-administration and restraint
      induced anxiety using the elevated plus maze. Intra-CeA URB597 significantly
      reduced alcohol self-administration in msP but not in Wistar rats. Intra
      basolateral amygdala URB597 also attenuated alcohol drinking in msPs, although
      the effect was less pronounced relative to CeA treatment. In contrast, control
      experiments administering URB597 into the ventral tegmental area produced no
      genotypic differences in drinking. We also found that URB597 treatment in the CeA
      significantly reduced the anxiogenic effects of restraint stress in msPs,
      although no effects were detected in Wistars. Dysregulation of FAAH regulated
      systems in the major output region of the amygdala may drive the propensity for
      co-morbid expression of anxiety and excessive alcohol use.

PMID- 29071768
TI  - Protective effect of Salvianolic acid A on ischaemia-reperfusion acute kidney
      injury in rats through protecting against peritubular capillary endothelium
      damages.
AB  - Renal ischaemia-reperfusion (I/R) injury is the most common cause of acute kidney
      injury (AKI). Peritubular capillary (PTC) endothelium damages are an important
      pathogenesis during I/R AKI. Salvianolic acid A (SAA) possesses various
      pharmacological activities. The study investigated whether SAA ameliorated I/R
      AKI through protecting against PTC endothelium damages. Male Sprague-Dawley rats
      were divided into 6 groups: control, sham, I/R, and I/R plus SAA (2.5, 5, 10
      mg/kg) groups. Rats were subjected to bilateral renal pedicle clamping for 60
      min, and killed at 24 hr after reperfusion. Kidney injury, PTC endothelium
      damages and factors affecting PTC endothelium were evaluated. SAA significantly
      decreased blood urea nitrogen and serum creatinine levels, and reduced urine
      kidney injury molecule-1 concentration. Simultaneously, SAA alleviated
      histological damages, prevented PTC endothelium damages, preserved the density of
      PTC and improved renal hypoxia. Furthermore, SAA inhibited platelet activation,
      elevated Klotho protein expression and up-regulated vascular endothelial growth
      factor A expression. Overall, SAA has protective effects on AKI induced by I/R.
      Preventing PTC endothelium damages and preserving PTC integrity to improve the
      renal hypoxia may be the ways for SAA to ameliorate AKI. All these indicate that
      SAA is likely to be a promising agent for AKI.

PMID- 29071771
TI  - A Multivalent Structure-Specific RNA Binder with Extremely Stable Target Binding
      but Reduced Interaction with Nonspecific RNAs.
AB  - By greatly enhancing binding affinities against target biomolecules, multivalent
      interactions provide an attractive strategy for biosensing. However, there is
      also a major concern for increased binding to nonspecific targets by multivalent
      binding. A range of charge-engineered probes of a structure-specific RNA binding
      protein PAZ as well as multivalent forms of these PAZ probes were constructed by
      using diverse multivalent avidin proteins (2-mer, 4-mer, and 24-mer). Increased
      valency vastly enhanced the binding stability of PAZ to structured target RNA.
      Surprisingly, nonspecific RNA binding of multivalent PAZ can be reduced even
      below that of the PAZ monomer by controlling negative charges on both PAZ and
      multivalent avidin scaffolds. The optimized 24-meric PAZ showed nearly
      irreversible binding to target RNA with negligible binding to nonspecific RNA,
      and this ultra-specific 24-meric PAZ probe allowed SERS detection of intact
      microRNAs at an attomolar level.

PMID- 29071770
TI  - The child's behavior during inhalational induction and its impact on the
      anesthesiologist's sevoflurane exposure.
AB  - BACKGROUND: Sevoflurane is commonly used for inhalational inductions in children,
      but the personnel's exposure to it is potentially harmful. Guidance to reduce gas
      pollution refers mainly to technical aspects, but the impact of the child's
      behavior has not yet been studied. AIMS: The purpose of this study was to
      determine how child behavior, according to the Frankl Behavioral Scale, affects
      the amount of waste sevoflurane in anesthesiologists' breathing zones. METHODS:
      Sixty-eight children aged 36-96 months undergoing elective ENT surgery were
      recruited for this prospective, observational investigation. After oral midazolam
      premedication (0.5 mg/kg body weight), patients obtained sevoflurane using a
      facemask with an inspiratory concentration of 8 Vol.% in 100% oxygen (flow 10
      L/min). Ventilation was manually supported and a venous catheter was placed. The
      inspiratory sevoflurane concentration was reduced, and remifentanil and propofol
      were administered before the facemask was removed and a cuffed tracheal tube
      inserted. The child's behavior toward the operating room personnel during
      induction was evaluated by the anesthesiologist (Frankl Behavioral Scale: 1-2 =
      negative behavior, 3-4 = positive behavior). During induction mean (c-mean) and
      maximum (c-max), sevoflurane concentrations were determined in the
      anesthesiologist's breathing zone by continuous photoacoustic gas monitoring.
      RESULTS: Mean and maximum sevoflurane concentrations were c-mean = 4.38 +/- 4.02
      p.p.m and c-max = 70.06 +/- 61.08 p.p.m in patients with positive behaviors and
      sufficient premedications and c-mean = 12.63 +/- 8.66 p.p.m and c-max = 242.86 +/
      139.91 p.p.m in children with negative behaviors and insufficient premedications
      (c-mean: P < .001; c-max: P < .001). CONCLUSION: Negative behavior was
      accompanied by significantly higher mean and maximum sevoflurane concentrations
      in the anesthesiologist's breathing zone compared with children with positive
      attitudes. Consequently, the status of premedication influences the amount of
      sevoflurane pollution in the air of operating rooms.

PMID- 29071772
TI  - The Ti3 AlC2 MAX Phase as an Efficient Catalyst for Oxidative Dehydrogenation of
      n-Butane.
AB  - Dehydrogenation or oxidative dehydrogenation (ODH) of alkanes to produce alkenes
      directly from natural gas/shale gas is gaining in importance. Ti3 AlC2 , a MAX
      phase, which hitherto had not been used in catalysis, efficiently catalyzes the
      ODH of n-butane to butenes and butadiene, which are important intermediates for
      the synthesis of polymers and other compounds. The catalyst, which combines both
      metallic and ceramic properties, is stable for at least 30 h on stream, even at
      low O2 :butane ratios, without suffering from coking. This material has neither
      lattice oxygens nor noble metals, yet a unique combination of numerous defects
      and a thin surface Ti1-y Aly O2-y/2 layer that is rich in oxygen vacancies makes
      it an active catalyst. Given the large number of compositions available, MAX
      phases may find applications in several heterogeneously catalyzed reactions.

PMID- 29071774
TI  - CT versus thoracic ultrasound for discriminating uncomplicated and complicated
      parapneumonic pleural effusions - Reply.

PMID- 29071773
TI  - Recent Developments of All-Solid-State Lithium Secondary Batteries with Sulfide
      Inorganic Electrolytes.
AB  - Due to the increasing demand of security and energy density, all-solid-state
      lithium ion batteries have become the promising next-generation energy storage
      devices to replace the traditional liquid batteries with flammable organic
      electrolytes. In this Minireview, we focus on the recent developments of sulfide
      inorganic electrolytes for all-solid-state batteries. The challenges of
      assembling bulk-type all-solid-state batteries for industrialization are
      discussed, including low ionic conductivity of the present sulfide electrolytes,
      high interfacial resistance and poor compatibility between electrolytes and
      electrodes. Many efforts have been focused on the solutions for these issues.
      Although some progresses have been achieved, it is still far away from practical
      application. The perspectives for future research on all-solid-state lithium ion
      batteries are presented.

PMID- 29071775
TI  - The Metal-Support Interaction Concerning the Particle Size Effect of Pd/Al2 O3 on
      Methane Combustion.
AB  - The particle size effect of Pd nanoparticles supported on alumina with various
      crystalline phases on methane combustion was investigated. Pd/theta, alpha-Al2 O3
      with weak metal-support interaction showed a volcano-shaped dependence of the
      catalytic activity on the size of Pd particles, and the catalytic activity of the
      strongly interacted Pd/gamma-Al2 O3 increased with the particle size. Based on a
      structural analysis of Pd nanoparticles using CO adsorption IR spectroscopy and
      spherical aberration-corrected scanning/transmission electron microscopy, the
      dependence of catalytic activity on Pd particle size and the alumina crystalline
      phase was due to the fraction of step sites on Pd particle surface. The
      difference in fraction of the step site is derived from the particle shape, which
      varies not only with Pd particle size but also with the strength of metal-support
      interaction. Therefore, this interaction perturbs the particle size effect of
      Pd/Al2 O3 for methane combustion.

PMID- 29071776
TI  - Clinical characteristics of hepatocellular carcinoma patients with normal serum
      alpha-fetoprotein level: A study of 112 consecutive cases.
AB  - BACKGROUND: Serum alpha-fetoprotein (AFP) level is normal in 30-40% of
      hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and
      clinical outcome is limited. The purpose of this observational study was to
      determine the clinical presentation, biological behavior and outcome of HCC
      patients with normal AFP level. METHODS: Data of 112 consecutive HCC patients
      with normal AFP level were analyzed retrospectively. Statistical analysis
      including survival and factors associated with serum AFP level were performed by
      Kaplan-Meier method and t-test, respectively. RESULTS: Hepatitis B virus
      infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a
      mean 52 +/- 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall
      survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3
      years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%,
      respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases.
      Significant difference in OS was observed among patients with BCLC stage 0-D
      diseases, P < 0.05. Using 8.78 ng/mL as the cut off value, serum AFP level
      elevated beyond normal figure during follow-up (AFP conversion) in 16 patients,
      which related with deterioration of liver function, quantitative changes of T
      helper cell subsets, rapid tumor progression and shorter survival. Patients with
      sustained normal AFP level had better survival than patients with AFP conversion,
      P < 0.05. There was significant difference between the time of diagnosis with HCC
      to serum AFP level elevation and the time of AFP elevation to death, P < 0.05.
      CONCLUSION: Prognosis of HCC patients with normal AFP level was relatively
      optimal. Serum AFP level elevation during follow-up was significantly associated
      with clinical outcome in terms of OS.

PMID- 29071777
TI  - Bar versus ball attachments for implant-supported overdentures in complete
      edentulism: A systematic review.
AB  - BACKGROUND: Implant-supported overdenture is one of the most predictable
      treatment options used in complete edentulism. However, differences have been
      reported between bar and ball attachments used to retain overdentures in terms of
      patient satisfaction and prosthesis retention. PURPOSE: The purpose of this study
      is to compare the effectiveness of bar and ball attachments for conventionally
      loaded implant-supported overdentures in completely edentulous patients to
      improve patient satisfaction and prosthesis retention. MATERIALS AND METHODS: We
      conducted the review according to the Cochrane methods and following MECIR
      standards. We searched Cochrane Oral Health Group Trial register, Cochrane
      Central Register of Controlled Trials, MEDLINE, and the WHO ICTRP (March 31,
      2017). Two review authors assessed trials for inclusion and risk of bias,
      extracted data, and checked for accuracy. We have expressed results as risk ratio
      or mean differences, together with their 95% confidence intervals. RESULTS: We
      included 10 trials (465 participants). After 5 y, one trial reported higher
      patient satisfaction when bar attachment was used (MD 1.30, 95% CI 0.20-2.40),
      and reported no difference between both systems in prosthesis retention (MD 
      0.90, 95% CI -1.90 to 0.10). Two trials reported no implant failures after 1 and
      5 y in both attachments. Downgrading of evidence was based on the unclear risk of
      bias of included studies and the wide CI crossing the line of no effect.
      CONCLUSIONS: There is insufficient evidence to support bar or ball attachment to
      be used with implant-supported overdentures in completely edentulous patients to
      improve patient satisfaction and prosthesis retention (PROSPERO
      2014:CRD42014014594).

PMID- 29071778
TI  - Isolation of ellagic acid from pomegranate peel extract by hydrophobic
      interaction chromatography using graphene oxide grafted cotton fiber adsorbent.
AB  - Ellagic acid, a natural polyphenol, was isolated from pomegranate peel extract by
      hydrophobic interaction using graphene oxide grafted cotton fiber as a stationary
      adsorbent. The grafted graphene oxide moieties served as hydrophobic interaction
      binding sites for ellagic acid adsorption. The graphene oxide grafted cotton
      fiber was made into a membrane-like sheet in order to complete ellagic acid
      purification by using a binding-elution mode. The effects of operational
      parameters, such as the composition of the binding buffer/elution buffer, buffer
      pH, and buffer concentration, on the isolation process were investigated. It was
      found that 5 mmol/L sodium carbonate aqueous solution is a proper-binding buffer,
      and sodium hydroxide aqueous solution ranging from 0.04 to 0.06 mol/L is a
      suitable elution solution for ellagic acid purification. Under the optimized
      condition, the purity of ellagic acid increased significantly from 7.5% in the
      crude extract to 75.0-80.0%. The pH value was found to be a key parameter that
      determines the adsorption and desorption of ellagic acid. No organic solvent is
      involved in the entire purification process. Thus, a simple and environmentally
      friendly method is established for ellagic acid purification using a graphene
      oxide-modified biodegradable and bio-sourced fibrous adsorbent.

PMID- 29071779
TI  - Risk factors and clinical outcomes of pediatric liver transplant recipients with
      post-transplant lymphoproliferative disease in a multi-ethnic Asian cohort.
AB  - BACKGROUND: We aimed to evaluate clinical characteristics, risk factors, and
      disease outcomes for liver transplant recipients (LTR) with post-transplant
      lymphoproliferative disease (PTLD) at our center. METHODS: Retrospective review
      of data of all pediatric LTR (1991-2015) was conducted. RESULTS: The overall
      incidence of PTLD was 16.4% (18/110), the majority (13/18) were early lesions,
      while 3/18 were polymorphic/monomorphic PTLD. The risk factors significant on
      univariate analysis were as follows: mean age (years) at transplant (1.66 vs
      4.76, P = .006); age <2 years at transplant (odds ratio [OR] 3.53 [95% confidence
      interval [CI]: 1.16-10.73], P = .026); cytomegalovirus (CMV) primary infection
      (OR 11.39 [95% CI: 3.44-37.7], P < .001); recipient CMV seronegativity (OR 7.50
      [95% CI: 2.02-27.78], P = .003); presence of CMV end-organ disease (OR 4.00 [95%
      CI: 1.22-13.16], P = .022); Chinese ethnicity; and higher mean duration of
      intravenous ganciclovir prophylaxis. In multivariate analysis, CMV primary
      infection (OR 5.22 [95% CI: 1.25-21.87], P = .024), CMV seronegativity (OR 5.91
      [95% CI: 1.13-30.90, P = .035]), and having acute cellular rejections (ACR) prior
      to PTLD (OR 5.53 [95% CI: 1.43-21.48, P = .013]) were significant risk factors
      for PTLD, with the latter two factors having a synergistic effect in increasing
      PTLD risk in a stratified analysis. The final multivariate model in predicting
      the risk of PTLD, utilizing CMV primary infection, recipient CMV seronegativity,
      and ACR before PTLD as predictive variables, was statistically significant
      (likelihood ratio chi square statistic = 25.18, P < .0001 with df = 3).
      CONCLUSIONS: We report a unique clinicopathologic and risk factor profile in our
      cohort-early lesion PTLD accounts for the majority and the incidence of
      monomorphic PTLD remains low. In addition, we show a synergism between CMV
      naivety and ACR on PTLD risk, a higher prevalence of gastrointestinal
      manifestations, and a lack of significant association with Epstein-Barr virus
      seronegativity.

PMID- 29071780
TI  - Layer-by-Layer Assembled Conductive Metal-Organic Framework Nanofilms for Room
      Temperature Chemiresistive Sensing.
AB  - The utility of electronically conductive metal-organic frameworks (EC-MOFs) in
      high-performance devices has been limited to date by a lack of high-quality thin
      film. The controllable thin-film fabrication of an EC-MOF, Cu3 (HHTP)2 ,
      (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene), by a spray layer-by-layer liquid
      phase epitaxial method is reported. The Cu3 (HHTP)2 thin film can not only be
      precisely prepared with thickness increment of about 2 nm per growing cycle, but
      also shows a smooth surface, good crystallinity, and high orientation. The
      chemiresistor gas sensor based on this high-quality thin film is one of the best
      room-temperature sensors for NH3 among all reported sensors based on various
      materials.

PMID- 29071781
TI  - Local recurrence is correlated with decreased overall survival in patients with
      intermediate high-grade localized primary soft tissue sarcoma of extremity and
      abdominothoracic wall.
AB  - AIM: The aim of this study was to determine the effect of local recurrence on
      overall survival in patients with intermediate high-grade localized primary soft
      tissue sarcoma (STS) of extremity and abdominothoracic wall. METHODS: This
      retrospective study identified 133 consecutive patients with intermediate high
      grade localized primary STS of extremity and abdominothoracic wall from January
      2000 to July 2010. Survival curves were constructed by the Kaplan-Meier method
      and log-rank test was used to assess statistical significance. Hazard ratios
      (HRs) were calculated based on multivariable Cox logistic regression method.
      RESULTS: The 5-year cumulative incidence of local recurrence was 26.0% with a
      median follow-up of 68 months (range, 5-127 months). The univariate analysis
      showed that local recurrence was associated with decreased overall survival, with
      5-year overall survival of 80.5% and 53.6% in the no local recurrence patients
      and local recurrence patients, respectively (P = 0.001). The multivariate
      analysis demonstrated that local recurrence was a negative prognostic factor for
      overall survival (HR = 2.115, 95% confidence interval [CI] 1.036-4.319, P =
      0.040). Radiotherapy significantly reduced local recurrence compared with surgery
      alone (HR = 0.387, 95% CI 0.180-0.877, P = 0.019), while larger tumor size (HR =
      3.184, 95% CI 1.351-7.506 P = 0.008) was correlated with higher rate of local
      recurrence. CONCLUSION: Local recurrence in patients with intermediate high-grade
      localized primary STS is associated with decreased overall survival.

PMID- 29071782
TI  - An Exfoliated 2D Egyptian Blue Nanosheet for Highly Selective Enrichment of Multi
      phosphorylated Peptides in Mass Spectrometric Analysis.
AB  - Phosphopeptide enrichment is essential for the phosphoprotein profiling, due to
      the low abundance in complex biological samples. Moreover, selective binding of
      multi-phosphopeptides over mono-phosphopeptides is rarely established, but
      strongly needed in real sample analysis, especially for the investigation of cell
      behaviors with the multisite phosphorylation cascades. Here two-dimensional (2D)
      nanosheets were synthesized of Egyptian blue (CaCuSi4 O10 ), the well-known
      ancient pigment, and its analogues (SrCuSi4 O10 and BaCuSi4 O10 ), which were
      employed in the enrichment of phosphopeptides for the first time. Surprisingly,
      the 2D CaCuSi4 O10 nanosheet was highly selective towards multi-phosphopeptides
      without enriching the mono-phosphorylated peptides in a wide range of acidic
      conditions or buffer compositions. Meanwhile, the SrCuSi4 O10 and BaCuSi4 O10
      nanosheet analogues do not exhibit this unique selectivity. Moreover, the
      ultrathin and well-defined 2D morphology, with abundant CaII , of Egyptian blue
      nanosheet was applied in cortical samples of forebrain specific PDK1 conditional
      knockout mice and their age-matched littermate controls, that are associated with
      Alzheimer's disease. The as-prepared 2D CaCuSi4 O10 nanosheet not only showed
      specific selectivity, but also exhibited high sensitivity (detection limit of
      4*10-7  m).

PMID- 29071783
TI  - Age is not a good predictor of irreversibility of pulmonary hypertension in
      congenital cardiac malformations with left-to-right shunt.
AB  - OBJECTIVE: Congenital cardiac malformations with high pulmonary blood flow and
      pressure due to left-to-right shunts are usually repaired in early infancy for
      both the benefits of early relief of heart failure and the fear that the
      concomitant pulmonary hypertension may become irreversible unless these defects
      are corrected at an early age. Age, however, has been a poor predictor of
      irreversibility of pulmonary hypertension in our experience, which is presented
      here. DESIGN: A retrospective observational study. We defined "late" as age >=2
      years. We examined clinical, echocardiographic, and hemodynamic data from all
      patients aged >=2 years with such malformations referred to us from 2004 untill
      2015. SETTING: Department of Pediatric Cardiology and Cardiac Surgery, University
      Hospital of Vaud, Lausanne, Switzerland. PATIENTS: There were 39 patients, aged 2
      35 years (median: 5 years), without chromosomal abnormalities. All had
      malformations amenable to biventricular repair, and all had high systolic right
      ventricular pressures by echocardiography prior to referral. INTERVENTIONS: All
      patients underwent catheterization for assessment of pulmonary hypertension. If
      this was reversible, surgical correction was offered. OUTCOME MEASURES: (1)
      Operability based on reversibility of pulmonary hypertension. (2) When surgery
      was offered, mortality and evidence of persisting postoperative pulmonary
      hypertension were examined. RESULTS: Eighteen patients had no pulmonary
      hypertension, 5 of variable ages were inoperable due to irreversible pulmonary
      hypertension, and 16 had reversible pulmonary hypertension. Therefore, 34
      patients underwent corrective surgery, with no immediate or late mortality.
      Pulmonary arterial and right ventricular pressures decreased noticeably in all
      operated patients. This is sustained to date; they are all asymptomatic with no
      echocardiographic evidence of pulmonary hypertension at a median follow-up of 7
      years (range 2-13 years). CONCLUSIONS: Pulmonary hypertension may still be
      reversible in many surprisingly old patients with left-to-right shunt lesions,
      who may therefore still be operable.

PMID- 29071784
TI  - Simultaneous determination of niacin and pyridoxine at trace levels by using
      diode array high-performance liquid chromatography and liquid chromatography with
      quadrupole time-of-flight tandem mass spectrometry.
AB  - A highly sensitive and simple diode-array high-performance liquid chromatography
      and liquid chromatography with quadrupole time-of-flight tandem mass spectrometry
      method was developed for the simultaneous determination of niacin and pyridoxine
      in pharmaceutical drugs, tap water, and wastewater samples. To determine the in
      vivo behavior of niacin and pyridoxine, analytes were subjected to simulated
      gastric conditions. The calibration plots of the diode-array high-performance
      liquid chromatography and liquid chromatography with quadrupole time-of-flight
      tandem mass spectrometry method showed good linearity over a wide concentration
      range with close to 1.0 correlation coefficients for both analytes. The limit of
      detection/limit of quantitation values for liquid chromatography quadrupole time
      of-flight tandem mass spectrometry analysis were 1.98/6.59 and 1.3/4.4 MUg/L for
      niacin and pyridoxine, respectively, while limit of detection/limit of
      quantitation values for niacin and pyridoxine in high-performance liquid
      chromatography analysis were 3.7/12.3 and 5.7/18.9 MUg/L, respectively. Recovery
      studies were also performed to show the applicability of the developed methods,
      and percentage recovery values were found to be 90-105% in tap water and 94-97%
      in wastewater for both analytes. The method was also successfully applied for the
      qualitative and quantitative determination of niacin and pyridoxine in drug
      samples.

PMID- 29071785
TI  - Simultaneous determination of amlodipine and metoprolol in their combined dosage
      form using a synchronous fluorescence spectrofluorimetric method.
AB  - Highly sensitive, rapid, accurate and precise synchronous fluorescence
      spectrofluorimetric method has been developed for simultaneous analysis of a
      mixture of amlodipine (AMD) and metoprolol (MET). The method relies on measuring
      the relative synchronous fluorescence intensity of both drugs at Deltalambda of
      90 nm in acetate buffer solution at pH 5. The experimental parameters influencing
      the developed method were investigated and optimized. The method was linear over
      the ranges 0.2-2 MUg/ml and 0.5-10 MUg/ml for AMD and MET, respectively. The
      limits of detection were 50 ng/ml for AMD and 130 ng/ml for MET while the limits
      of quantitation were 150 ng/ml for AMD and 390 ng/ml for MET. The developed
      method was applied successfully for the determination of the two drugs in their
      co-formulated tablet. The mean percent recoveries were found to be 100.51 and
      99.57 for AMD and MET, respectively.

PMID- 29071786
TI  - Synthesis and characterization of KCe(PO3 )4 doped with some lanthanide
      activators.
AB  - KCe(PO3 )4 doped with Dy3+ ,Tb3+ ,Yb3+ and Nd3+ phosphors were synthesized by a
      solid state diffusion method. The prepared samples were characterized by X-ray
      diffraction and photoluminescence. KCe(PO3 )4 exhibits emission in ultraviolet
      (UV) region which indicates weak Ce3+ -Ce3+ interaction. The Ce3+ -Ce3+ energy
      transfer is not efficient. In light of this, energy transfer from Ce3+ to other
      lanthanides like Dy3+ , Tb3+ ,Yb3+ and Nd3+ is rather surprising.

PMID- 29071787
TI  - Synthesis of Pyrrole-Fused Corannulenes: 1,3-Dipolar Cycloaddition of Azomethine
      Ylides to Corannulene.
AB  - In the long history of corannulene chemistry, the 1,3-dipolar cycloaddition to
      corannulene is unprecedented. Reported herein is the 1,3-dipolar cycloaddition of
      a polycyclic aromatic azomethine ylide to corannulene, a reaction which occurs
      exclusively at the rim bond of corannulene, from the convex side in an exo
      fashion. The cycloadducts were successfully converted, by successive oxidative
      dehydrogenation, into pyrrole-fused corannulenes, which exhibited pronounced
      solvatofluorochromism.

PMID- 29071788
TI  - Rhodium(II)- or Copper(I)-Catalyzed Formal Intramolecular Carbene Insertion into
      Vinylic C(sp2 )-H Bonds: Access to Substituted 1H-Indenes.
AB  - A rhodium(II)- or copper(I)-catalyzed formal intramolecular carbene insertion
      into vinylic C(sp2 )-H bonds is reported herein. This method provides
      straightforward access to 1H-indenes with high efficiency and excellent
      functional-group compatibility. Mechanistically, the reaction is proposed to
      involve the following sequence: metal carbene formation, intramolecular
      nucleophilic addition of the double bond to the electron-deficient carbene carbon
      atom, dearomatization, and finally a 1,5-H shift.

PMID- 29071789
TI  - Online hyphenation of extraction, Sephadex LH-20 column chromatography, and high
      speed countercurrent chromatography: A highly efficient strategy for the
      preparative separation of andrographolide from Andrographis paniculata in a
      single step.
AB  - A novel isolation strategy, online hyphenation of ultrasonic extraction, Sephadex
      LH-20 column chromatography combined with high-speed countercurrent
      chromatography, was developed for pure compounds extraction and purification.
      Andrographolide from Andrographis paniculata was achieved only in a single step
      purification protocol via the present strategy. The crude powder was ultrasonic
      extracted and extraction was pumped into Sephadex LH-20 column directly to cut
      the nontarget fractions followed by the second-dimensional high-speed
      countercurrent chromatography, hyphenated by a six-port valve equipped at the
      post-end of Sephadex LH-20 column, for the final purification. The results
      yielded andrographolide with the amount of 1.02 mg and a purity of 98.5% in a
      single step, indicating that the present method is effective to harvest target
      compound from medicinal plant.

PMID- 29071790
TI  - Stress and quality of life among parents of children with congenital heart
      disease referred for psychological services.
AB  - OBJECTIVE: The study examined parent stress and health-related quality of life
      (HRQOL) among families of children with congenital heart disease (CHD) referred
      for psychological services. METHODS: Parents of 54 children (85% boys) aged 3 to
      13 (Mage  = 7.48, SD = 2.38) completed measures to assess parenting stress
      (Parenting Stress Index - Short Form; Pediatric Inventory for Parents) and the
      PedsQL Family Impact Module. Medical information was retrieved from medical
      record review. RESULTS: Half of parents of children with single ventricle anatomy
      had clinically significant levels of parenting stress. Parents of children with
      single ventricle anatomy reported more frequent illness-related stress and more
      difficulty dealing with illness-related stress than parents of children with two
      ventricle anatomy. Younger gestational age at birth and referral for attention or
      behavior problems were associated with greater likelihood of parent at-risk
      psychosocial functioning. CONCLUSIONS: Among children referred for psychological
      services, many parents report significant stress and significant negative impact
      of the child's medical condition on the family. Results underscore the need to
      consider assessing parent psychosocial functioning and providing additional
      support for parents of children with CHD.

PMID- 29071791
TI  - Current Status of Hepatitis C Virus-Infected Maintenance Hemodialysis Patients in
      Japan.
AB  - Complete recovery using interferon therapy in Japanese hepatitis C virus (HCV)
      infected dialysis patients is difficult to achieve because >70 % of the HCV
      genotypes observed in Japan are type 1. In 2016, new direct-acting antiviral
      drugs against HCV genotype 1 were reported to be effective and safe for HCV
      infected hemodialysis patients. Although new direct antiviral therapy has become
      available, no large-scale studies evaluating the status of HCV infection in
      Japanese hemodialysis patients have been conducted since 2007. Therefore, we
      conducted a questionnaire survey to determine the current status of HCV infection
      in patients. Our results indicated that the HCV antibody prevalence was 5.02 %,
      and HCV RNA prevalence was 72.3 %. Genotype testing revealed that 62.1 % of
      patients had HCV genotype 1. New direct antiviral therapy may improve the
      survival of Japanese HCV-infected dialysis patients.

PMID- 29071792
TI  - Behavioral Associations with Overweight in Low-Income Children.
AB  - OBJECTIVE: Food reinforcement (relative reinforcement value [RRV]), self-control
      (the ability to delay gratification [ATDG]), and eating outside of homeostatic
      need (eating in the absence of hunger [EAH]) are associated with
      overweight/obesity. These constructs have typically been studied in isolation in
      children, and little is known about how they interrelate and whether these
      associations differ by sex. The objective of this study is to investigate these
      associations by sex. METHODS: In a low-income sample of 230 7- to 10-year-old
      children, RRV, ATDG, and EAH were assessed. The model showing that elevated RRV,
      lower ATDG, and greater EAH are each independent, direct predictors of overweight
      in middle childhood was separately tested by sex. It was predicted that greater
      RRV and less ATDG would also have indirect effects on overweight through EAH. The
      association between RRV and ATDG was investigated. RESULTS: For girls, higher RRV
      was indirectly associated with overweight through EAH. For boys, no associations
      of RRV, ATDG, or EAH with overweight were significant. Finally, for girls, RRV
      and ATDG were significantly positively associated. CONCLUSIONS: In girls, higher
      food reinforcement appears to be an important contributor to overweight. During
      middle childhood, ATDG may be assessing food reinforcement rather than self
      control. Future studies are needed to identify the mechanisms underlying
      childhood overweight in boys.

PMID- 29071794
TI  - Posttranscriptional control of airway inflammation.
AB  - Acute inflammation in the lungs is a vital protective response, efficiently and
      swiftly eliminating inciters of tissue injury. However, in respiratory diseases
      characterized by chronic inflammation, such as chronic obstructive pulmonary
      disease and asthma, enhanced expression of inflammatory mediators leads to tissue
      damage and impaired lung function. Although transcription is an essential first
      step in the induction of proinflammatory genes, tight regulation of inflammation
      requires more rapid, flexible responses. Increasing evidence shows that such
      responses are achieved by posttranscriptional mechanisms directly affecting mRNA
      stability and translation initiation. RNA-binding proteins, microRNAs, and long
      noncoding RNAs interact with messenger RNA and each other to impact the stability
      and/or translation of mRNAs implicated in lung inflammation. Recent research has
      shown that these biological processes play a central role in the pathogenesis of
      several important pulmonary conditions. This review will highlight several
      posttranscriptional control mechanisms that influence lung inflammation and the
      known associations of derangements in these mechanisms with common respiratory
      diseases. WIREs RNA 2018, 9:e1455. doi: 10.1002/wrna.1455 This article is
      categorized under: RNA in Disease and Development > RNA in Disease RNA Structure
      and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions
      with Proteins and Other Molecules > Protein-RNA Interactions: Functional
      Implications RNA Turnover and Surveillance > Regulation of RNA Stability.

PMID- 29071793
TI  - Intramyocellular Lipid Droplet Size Rather Than Total Lipid Content is Related to
      Insulin Sensitivity After 8 Weeks of Overfeeding.
AB  - OBJECTIVE: Intramyocellular lipid (IMCL) is inversely related to insulin
      sensitivity in sedentary populations, yet no prospective studies in humans have
      examined IMCL accumulation with overfeeding. METHODS: Twenty-nine males were
      overfed a high-fat diet (140% caloric intake, 44% from fat) for 8 weeks. Measures
      of IMCL, whole-body fat oxidation from a 24-hour metabolic chamber, muscle
      protein extracts, and muscle ceramide measures were obtained before and after the
      intervention. RESULTS: Eight weeks of overfeeding did not increase overall IMCL.
      The content of smaller lipid droplets peripherally located in the myofiber
      decreased, while increases in larger droplets correlated inversely with glucose
      disposal rate. Overfeeding resulted in inhibition of Akt activity, which
      correlated with the reductions in smaller, peripherally located lipid droplets
      and drastic increases in ceramide content. Additionally, peripherally located
      lipid droplets were associated with more efficient lipid oxidation. Finally,
      participants who maintained a greater number of smaller, peripherally located
      lipid droplets displayed a better resistance to weight gain with overfeeding.
      CONCLUSIONS: These results show that lipid droplet size and location rather than
      mere IMCL content are important to understanding insulin sensitivity.

PMID- 29071795
TI  - Hemodynamic assessment of Perceval sutureless bioprosthesis by dobutamine stress
      echocardiography.
AB  - OBJECTIVES: The aim of this study was to evaluate the hemodynamic performance of
      a sutureless bioprosthesis under high workload at mid-term follow-up. METHODS:
      Thirty-two patients who underwent isolated aortic valve replacement with a
      Perceval sutureless bioprosthesis with a minimum follow-up of 1 year were
      enrolled in this study. S size prosthesis was deployed in 10 patients (31.3%), M
      size in 9 (28.1%), L size in 8 (25%) and XL size in 5 (15.6%). Effective orifice
      area (EOA), EOA index (EOAi), and transvalvular gradients were assessed at rest
      and during dobutamine stress echocardiography (DSE) a median of 19.5 months after
      surgery. RESULTS: Dobutamine stress echocardiography (DSE) significantly
      increased heart rate, stroke volume, ejection fraction, and transvalvular
      gradients (peak gradient, 24.0 +/- 7.6 vs 38.7 +/- 13.6 mm Hg, P < .001; mean
      gradient, 12.6 +/- 4.2 vs 19.8 +/- 8.3, P < .001). When compared to baseline,
      estimated valve areas significantly increased at follow-up (EOA, 1.48 +/- 0.46 vs
      2.06 +/- 0.67, P < .001; EOAi, 0.84 +/- 0.26 vs 1.17 +/- 0.37, P < .001). Mean
      percentage increase in EOAi was 40.3% +/- 28.0%. S size prostheses had the
      highest increase in EOA1, but the difference was not significant (S 46.0% +/-
      27.5% vs M 45.4% +/- 34.5% vs L 32.7% +/- 26.4% vs XL 32.1% +/- 20.5%, P = .66).
      Severe patient-prosthesis mismatch (EOAi <= 0.65 cm2 /m2 ) was present at rest in
      8 patients (25%), but only in one patient (3.1%) during DSE. CONCLUSIONS: The
      Perceval sutureless bioprosthesis demonstrated good hemodynamics at rest and
      under high workload. The significant increase in EOAi during DSE suggests the
      potential advantages of Perceval sutureless bioprostheses in case of small aortic
      annulus or when patient-prosthesis mismatch is anticipated.

PMID- 29071796
TI  - Counting on fine motor skills: links between preschool finger dexterity and
      numerical skills.
AB  - Finger counting is widely considered an important step in children's early
      mathematical development. Presumably, children's ability to move their fingers
      during early counting experiences to aid number representation depends in part on
      their early fine motor skills (FMS). Specifically, FMS should link to children's
      procedural counting skills through consistent repetition of finger-counting
      procedures. Accordingly, we hypothesized that (a) FMS are linked to early
      counting skills, and (b) greater FMS relate to conceptual counting knowledge
      (e.g., cardinality, abstraction, order irrelevance) via procedural counting
      skills (i.e., one-one correspondence and correctness of verbal counting).
      Preschool children (N = 177) were administered measures of procedural counting
      skills, conceptual counting knowledge, FMS, and general cognitive skills along
      with parent questionnaires on home mathematics and fine motor environment. FMS
      correlated with procedural counting skills and conceptual counting knowledge
      after controlling for cognitive skills, chronological age, home mathematics and
      FMS environments. Moreover, the relationship between FMS and conceptual counting
      knowledge was mediated by procedural counting skills. Findings suggest that FMS
      play a role in early counting and therewith conceptual counting knowledge.

PMID- 29071798
TI  - The protein corona on nanoparticles as viewed from a nanoparticle-sizing
      perspective.
AB  - Most surfaces of engineered nanoparticles (NPs) are reactive toward biomolecules.
      Therefore, whenever NPs become immersed in biological fluids, proteins and other
      biomolecules bind to the NP surface, forming an adsorption layer (biomolecular
      corona) that modifies the NPs' physicochemical properties and subsequent
      interactions with living systems. Its exploration is a formidable endeavor owing
      to the enormous diversity of engineered NPs in terms of their physicochemical
      properties and the vast number of biomolecules available in biofluids that may
      bind to NPs with widely different strengths. Significant progress has been made
      in our understanding of the biomolecular corona, but even very basic issues are
      still controversially debated. In fact, there are divergent views of its
      microscopic structure and dynamics, even on physical properties, such as its
      thickness. As an example, there is no agreement on whether proteins form
      monolayers or multilayers upon adsorption. In our quantitative studies of NP
      protein interactions by in situ fluorescence correlation spectroscopy (FCS) with
      highly defined model NPs and important serum proteins, we have universally
      observed protein monolayer formation around NPs under saturation or even
      oversaturation conditions. Here, we critically discuss biomolecular corona
      characterization using FCS and dynamic light scattering and identify challenges
      and future opportunities. Further careful, quantitative experiments are needed to
      elucidate the mechanisms of biomolecular corona formation and to characterize its
      structure. This article is categorized under: Nanotechnology Approaches to
      Biology > Nanoscale Systems in Biology.

PMID- 29071799
TI  - Body Mass Index Trajectories from Adolescence to Early Young Adulthood: Do
      Adverse Life Events Play a Role?
AB  - OBJECTIVE: The aim of this study was to investigate whether there are different
      classes of body mass index (BMI) development from early adolescence to young
      adulthood and whether these classes are related to the number of adverse life
      events children experienced. METHODS: Data were from the TRAILS (TRacking
      Adolescents' Individual Lives Survey) cohort (n = 2,218). Height and weight were
      objectively measured five times between participants' ages 10 to 12 years and 21
      to 23 years. Parents reported on the occurrence of adverse life events in their
      child's life in an interview when children were 10 to 12 years old. Unconditional
      and conditional growth mixture modeling was used for statistical analysis.
      RESULTS: "Normal weight" (75.1%), "late onset overweight" (20.1%), and "early
      onset overweight" classes (4.8%) were identified. In analyses unadjusted for
      additional covariates, children who experienced a higher number of adverse events
      had higher odds to be in the late onset overweight (OR [95% CI] = 1.08 [1.00
      1.17]) than the normal weight class, but the association was attenuated in
      analyses adjusted for additional covariates (OR [95% CI] = 1.07 [0.98-1.16]).
      CONCLUSIONS: Three BMI trajectory classes can be distinguished from early
      adolescence to young adulthood. The accumulation of adverse life events is not
      related to BMI trajectory class.

PMID- 29071800
TI  - National survey on image-guided radiotherapy practice in New Zealand.
AB  - INTRODUCTION: This survey aimed to assess the use of image-guided radiotherapy
      (IGRT) within New Zealand (NZ) and evaluate the quality of IGRT delivery. METHOD:
      All nine centres in NZ were invited to participate in an online survey in
      November 2015. Questions were asked on type of IGRT technologies available, IGRT
      use by tumour site and frequency of imaging. In addition, questions were asked in
      reference to the American Society for Radiation Oncology (ASTRO) White Paper
      recommendations on safe practice of IGRT. RESULTS: Seven of the nine centres
      (78%) responded. Kilovoltage cone-beam CT (CBCT), kilovoltage planar imaging and
      megavoltage electronic portal imaging were the most commonly used IGRT
      technologies. CBCT was most frequently used in gynaecology (100%), genitourinary
      (86%) and head and neck (86%) sites. Despite the availability of similar IGRT
      technologies, there was significant variation in their application between
      centres. All centres used online IGRT; however, the frequency of imaging varied
      across the tumour sites and individual centres. Daily online IGRT use ranged from
      43% to 86% across the tumour sites. Overall, there was good compliance by the NZ
      centres to the White Paper recommendations, with at least 71% reached for each
      element. However, the compliance rates for the individual centres ranged between
      50% and 100%. The most commonly identified barrier to IGRT use was lack of
      guidelines/education (43%). CONCLUSION: Image-guided radiotherapy is widely used
      in NZ; however, there is a wide variation in its application between centres.
      Detailed tumour site-specific, imaging modality-specific national guidelines will
      allow standardization of IGRT practices.

PMID- 29071797
TI  - Novel genetic variants in the P38MAPK pathway gene ZAK and susceptibility to lung
      cancer.
AB  - The P38MAPK pathway participates in regulating cell cycle, inflammation,
      development, cell death, cell differentiation, and tumorigenesis. Genetic
      variants of some genes in the P38MAPK pathway are reportedly associated with lung
      cancer risk. To substantiate this finding, we used six genome-wide association
      studies (GWASs) to comprehensively investigate the associations of 14 904 single
      nucleotide polymorphisms (SNPs) in 108 genes of this pathway with lung cancer
      risk. We identified six significant lung cancer risk-associated SNPs in two genes
      (CSNK2B and ZAK) after correction for multiple comparisons by a false discovery
      rate (FDR) <0.20. After removal of three CSNK2B SNPs that are located in the same
      locus previously reported by GWAS, we performed the LD analysis and found that
      rs3769201 and rs7604288 were in high LD. We then chose two independent
      representative SNPs of rs3769201 and rs722864 in ZAK for further analysis. We
      also expanded the analysis by including these two SNPs from additional GWAS
      datasets of Harvard University (984 cases and 970 controls) and deCODE (1319
      cases and 26 380 controls). The overall effects of these two SNPs were assessed
      using all eight GWAS datasets (OR = 0.92, 95%CI = 0.89-0.95, and P = 1.03 * 10-5
      for rs3769201; OR = 0.91, 95%CI = 0.88-0.95, and P = 2.03 * 10-6 for rs722864).
      Finally, we performed an expression quantitative trait loci (eQTL) analysis and
      found that these two SNPs were significantly associated with ZAK mRNA expression
      levels in lymphoblastoid cell lines. In conclusion, the ZAK rs3769201 and
      rs722864 may be functional susceptibility loci for lung cancer risk.

PMID- 29071803
TI  - Obesity and Associated Health Disparities Among Understudied Multiracial, Pacific
      Islander, and American Indian Adults.
AB  - OBJECTIVE: This study examined the state of obesity, diabetes, and associated
      health disparities among understudied multiracial, Native Hawaiian and Other
      Pacific Islander (NHOPI), and American Indian and Alaskan Native (AIAN) adults.
      METHODS: Aggregated data for 184,617 adults from the California Health Interview
      Survey (2005 to 2011) were analyzed to determine obesity, diabetes, poor/fair
      health, and physical disability prevalence by racial group. Logistic regressions
      controlling for age, gender, and key social determinants (education, marital
      status, poverty, health insurance) generated multiracial, NHOPI, and AIAN adults'
      odds ratios (ORs) for our targeted health conditions versus non-Hispanic white
      adults. RESULTS: Obesity, diabetes, and other targeted health conditions were
      highly prevalent among multiracial, NHOPI, and AIAN adults, who displayed
      significantly greater adjusted odds than non-Hispanic white adults for obesity
      (ORs = 1.2-1.9), diabetes (ORs = 1.6-2.4), poor/fair health (ORs = 1.4-1.7), and,
      with the exception of NHOPI adults, physical disability (ORs = 1.5-1.6).
      Multiracial and AIAN adults with obesity also had significantly higher adjusted
      odds of diabetes (OR = 1.5-2.6) than non-Hispanic white adults with obesity.
      CONCLUSIONS: Multiracial, NHOPI, and AIAN adults experience striking obesity
      related disparities versus non-Hispanic white adults, urging further disparities
      research with these vulnerable minority populations.

PMID- 29071802
TI  - Metabolic Benefits of Prior Weight Loss with and without Exercise on Subsequent 6
      Month Weight Regain.
AB  - OBJECTIVE: To determine the 6-month follow-up effects after intentional 6-month
      weight loss alone (WL) and after weight loss with aerobic exercise (AEX + WL) on
      body composition, glucose metabolism, and cardiovascular disease risk factors in
      older postmenopausal women and to identify the mechanisms for weight regain.
      METHODS: Women (n = 65, BMI > 25 kg/m2 ) underwent maximal oxygen consumption
      testing, dual-energy x-ray absorptiometry, computed tomography scans, and oral
      glucose tolerance tests before and after 6 months of AEX + WL or WL and at 12
      months ad libitum follow-up. Insulin sensitivity (M) (hyperinsulinemic-euglycemic
      clamp) was measured at baseline and 6 months. Thirty WL and thirty-five AEX + WL
      women completed a follow-up at 12 months. RESULTS: Similar weight loss was
      observed (-8%) in both groups from 0 to 6 months. Total fat mass, fat-free mass,
      visceral fat area, subcutaneous abdominal and midthigh fat areas, fasting
      glucose, insulin levels, homeostatic model assessment of insulin resistance (HOMA
      IR), insulin areas under the curve, and triglyceride levels decreased similarly
      after WL and AEX + WL and remained lower at 12 months than at baseline, despite
      weight regain at 12 months. Initial M was associated with weight regain (r = 
      0.40, P < 0.01). Weight regain was related to independent changes in leptin and
      HOMA-IR from 6 to 12 months in a multiple regression model (r = 0.77, P <
      0.0001). CONCLUSIONS: Reductions in body fat and improvements in insulin
      sensitivity after AEX + WL and WL were maintained at 12 months despite modest
      weight regain. Baseline insulin resistance partially predicted the magnitude of
      weight regain in postmenopausal women.

PMID- 29071804
TI  - Contributions of Academic Emergency Medicine Programs to U.S. Health Care:
      Summary of the AAAEM-AACEM Benchmarking Data.
AB  - OBJECTIVES: The societal contribution of emergency care in the United States has
      been described. The role and impact of academic emergency departments (EDs) has
      been less clear. Our report summarizes the results of a benchmarking effort
      specifically focused on academic emergency medicine (EM) practices. METHODS: From
      October through December 2016, the Academy of Academic Administrators of
      Emergency Medicine (AAAEM) and the Association of Academic Chairs of Emergency
      Medicine (AACEM) jointly administered a benchmarking survey to allopathic,
      academic departments and divisions of emergency medicine. Participation was
      voluntary and nonanonymous. The survey queried various aspects of the three
      components of the tripartite academic mission: clinical care, education and
      research, and faculty effort and compensation. Responses reflected a calendar
      year from July 1, 2015, to June 30, 2016. RESULTS: Of 107 eligible U.S.
      allopathic, academic departments and divisions of emergency medicine, 79 (74%)
      responded to the survey overall, although individual questions were not always
      answered by all responding programs. The 79 responding programs reported
      6,876,189 patient visits at 97 primary and affiliated academic clinical sites. A
      number of clinical operations metrics related to the care of these patients at
      these sites are reported in this study. All responding programs had active
      educational programs for EM residents, with a median of 37 residents per program.
      Nearly half of the overall respondents reported responsibility for teaching
      medical students in mandatory EM clerkships. Fifty-two programs reported research
      and publication activity, with a total of $129,494,676 of grant funding and 3,059
      publications. Median faculty effort distribution was clinical effort, 66.9%;
      education effort, 12.7%; administrative effort, 12.0%; and research effort, 6.9%.
      Median faculty salary was $277,045. CONCLUSIONS: Academic EM programs are
      characterized by significant productivity in clinical operations, education, and
      research. The survey results reported in this investigation provide appropriate
      benchmarking for academic EM programs because they allow for comparison of
      academic programs to each other, rather than nonacademic programs that do not
      necessarily share the additional missions of research and education and may have
      dissimilar working environments.

PMID- 29071801
TI  - Common oral complications of head and neck cancer radiation therapy: mucositis,
      infections, saliva change, fibrosis, sensory dysfunctions, dental caries,
      periodontal disease, and osteoradionecrosis.
AB  - Patients undergoing radiation therapy for the head and neck are susceptible to a
      significant and often abrupt deterioration in their oral health. The oral
      morbidities of radiation therapy include but are not limited to an increased
      susceptibility to dental caries and periodontal disease. They also include
      profound and often permanent functional and sensory changes involving the oral
      soft tissue. These changes range from oral mucositis experienced during and soon
      after treatment, mucosal opportunistic infections, neurosensory disorders, and
      tissue fibrosis. Many of the oral soft tissue changes following radiation therapy
      are difficult challenges to the patients and their caregivers and require life
      long strategies to alleviate their deleterious effect on basic life functions and
      on the quality of life. We discuss the presentation, prognosis, and management
      strategies of the dental structure and oral soft tissue morbidities resulting
      from the administration of therapeutic radiation in head and neck patient. A case
      for a collaborative and integrated multidisciplinary approach to the management
      of these patients is made, with specific recommendation to include knowledgeable
      and experienced oral health care professionals in the treatment team.

PMID- 29071805
TI  - Practical strategies and perceptions from community pharmacists following their
      experiences with conducting pharmacy practice research: a qualitative content
      analysis.
AB  - OBJECTIVES: While prior research identified barriers to conducting research in
      community pharmacies, there remains a need to better understand facilitators to
      ensure successful collaborations between academic researchers and pharmacists.
      Our objective was to determine the experiences and perspectives of community
      pharmacists who have recently conducted a pharmacy practice-based research study
      to gain in-depth understanding of challenges as well as facilitators and identify
      strategies and solutions. METHODS: We conducted a qualitative study involving one
      on-one semi-structured telephone interviews with community pharmacists following
      the completion of a practice-based research study in their pharmacies. Interview
      transcripts were analysed using inductive content analysis involving open coding,
      creating categories and abstraction into final themes. KEY FINDINGS: Eleven
      pharmacists participated in the qualitative interviews. We identified six major
      themes including: (1) barriers (e.g. time constraints); (2) facilitators (e.g.
      ideal pharmacy layout); (3) support and resources from academic researchers (e.g.
      helpfulness of training, easy-to-use study materials); (4) pharmacist-initiated
      strategies for conducting research (beyond prior suggestions from researchers);
      (5) suggestions for future pharmacy practice research; and (6) motivation for
      conducting pharmacy practice research. These findings informed practical
      strategies targeted at academic researchers and pharmacists, respectively, to
      facilitate the conduct of research in community pharmacists across various stages
      of the research process. CONCLUSIONS: Our study adds to better understanding of
      community pharmacists' perspectives on conducting research and identifies
      practical solutions that can be readily implemented by academic researchers and
      pharmacists participating in research.

PMID- 29071807
TI  - The Effect of Methylammonium Iodide on the Supersaturation and Interfacial Energy
      of the Crystallization of Methylammonium Lead Triiodide Single Crystals.
AB  - It is very important to study the crystallization of hybrid organic-inorganic
      perovskites because their thin films are usually prepared from solution. The
      investigation on the growth of perovskite films is however limited by their
      polycrystallinity. In this work, methylammonium lead triiodide single crystals
      grown from solutions with different methylammonium iodide (MAI):lead iodide (PbI2
      ) ratios were investigated. We observed a V-shaped dependence of the
      crystallization onset temperature on the MAI:PbI2 ratio. This is attributed to
      the MAI effects on the supersaturation of precursors and the interfacial energy
      of the crystal growth. At low MAI:PbI2 ratio (<1.7), more MAI leads to the
      supersaturation of the precursors at lower temperature. At high MAI:PbI2 ratio,
      the crystal growing plans change from (100)-plane dominated to (001)-plane
      dominated. The latter have higher interfacial energy than the former, leading to
      a higher crystallization onset temperature.

PMID- 29071806
TI  - Efficacy and safety of amrubicin-based regimen used as first-line for extensive
      disease small-cell lung cancer: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Currently, amrubicin is used as first-line in the treatment of
      patients with small-cell lung cancer (SCLC). However, the effect of amrubicin
      based treatment in extensive-disease (ED) SCLC remains controversial. Thus, we
      conducted a meta-analysis of randomized controlled trials (RCTs) to assess the
      efficacy and safety of amrubicin-based regimen in the treatment of patients with
      ED-SCLC. METHODS: RCTs published in PubMed, Web of Science, Embase, and
      ClinicalTrials.gov were systematically reviewed. Eligible studies were these that
      evaluated the efficacy and safety profiles of amrubicin-based regimen in ED-SCLC.
      Outcomes included progression-free survival (PFS), overall survival (OS), overall
      response rate (ORR), and adverse events. Results were expressed with hazard ratio
      (HR) with 95% confidence intervals (CIs), and risk ratio (RR) with 95% CIs.
      RESULTS: Four RCTs involving a total of 740 patients met the inclusion criteria
      and were included in this meta-analysis. Amrubicin-based regimen was not
      associated with significantly prolonged PFS (HR = 1.07, 95% CI: 0.90-1.30; P =
      0.463) and OS (HR = 1.07, 95% CI: 0.89-1.29; P = 0.443) in patients with ED-SCLC.
      However, it significantly improved ORR (RR = 1.14, 95% CI: 1.04-1.25; P = 0.008).
      Subgroup analysis demonstrated that neither amrubicin alone nor in combination
      with cisplatin prolonged the PFS and OS, and only the combination therapy
      significantly increased ORR. The incidence of grade >=3 adverse events was
      comparable between amrubicin-containing and other treatment groups (RR = 1.42,
      95% CI: 0.78-2.58; P = 0.248). However, amrubicin-based treatment induced a
      significantly higher incidence of febrile neutropenia (RR = 3.32, 95% CI: 2.04
      5.41; P < 0.001), anemia (RR = 1.44, 95% CI: 1.06-1.97; P = 0.022), leukopenia
      (RR = 2.17, 95% CI: 1.41-3.33; P < 0.001), neutropenia (RR = 1.33, 95% CI: 1.04
      1.70; P = 0.021), and interstitial lung disease (RR = 1.58, 95% CI: 1.21-1.98; P
      < 0.001). CONCLUSION: Amrubicin-based regimen used as first-line had no survival
      benefits in patients with ED-SCLC. But it significantly improved ORR. Further
      well-conducted, large-scale trials are needed to validate these findings.

PMID- 29071808
TI  - Controllable Activation of Pd-G3 Palladacycle Precatalyst in the Presence of
      Thiosugars: Rapid Access to 1-Aminobiphenyl Thioglycoside Atropoisomers at Room
      Temperature.
AB  - A controllable method for the functionalization of XantPhos Pd-G3 precatalyst
      with thiosugars and thiols has been established. Under mild and operationally
      simple reaction conditions through just mixing of precatalyst and thiosugars
      (alpha- or beta-mono-, di- and poly-thiosugar derivatives) in water at 25 
      degrees C for 20 min, a series of 1-aminobiphenyl thioglycosides that are
      difficult to synthesize by classical methods has been synthesized in very high
      yields.

PMID- 29071809
TI  - Proportional Feedback Control of Energy Intake During Obesity Pharmacotherapy.
AB  - OBJECTIVE: Obesity pharmacotherapies result in an exponential time course for
      energy intake whereby large early decreases dissipate over time. This pattern of
      declining drug efficacy to decrease energy intake results in a weight loss
      plateau within approximately 1 year. This study aimed to elucidate the physiology
      underlying the exponential decay of drug effects on energy intake. METHODS:
      Placebo-subtracted energy intake time courses were examined during long-term
      obesity pharmacotherapy trials for 14 different drugs or drug combinations within
      the theoretical framework of a proportional feedback control system regulating
      human body weight. RESULTS: Assuming each obesity drug had a relatively constant
      effect on average energy intake and did not affect other model parameters, our
      model correctly predicted that long-term placebo-subtracted energy intake was
      linearly related to early reductions in energy intake according to a prespecified
      equation with no free parameters. The simple model explained about 70% of the
      variance between drug studies with respect to the long-term effects on energy
      intake, although a significant proportional bias was evident. CONCLUSIONS: The
      exponential decay over time of obesity pharmacotherapies to suppress energy
      intake can be interpreted as a relatively constant effect of each drug
      superimposed on a physiological feedback control system regulating body weight.

PMID- 29071810
TI  - Cancer Registry follow-up for 17 million person-years of a nationwide maternity
      cohort.
AB  - Population-based Finnish Maternity Cohort (FMC) comprises 2M first trimester sera
      collected from 1M women during 33 years. Informed consent is by the opt-out
      principle, and linkages with cancer and population registries provide a base for
      over time and over generation studies. Follow-up for 17M person-years by the end
      of 2014 can identify 39,700 cases of invasive cancer and 18,900 cases of
      premalignant breast and cervix lesions, and basal cell carcinoma diagnosed after
      serum sampling. For women with multiple pregnancies, serial samples taken before
      cancer diagnosis are available. Offspring of the women have developed more than
      4000 cancers. For 100,000 individuals, samples taken during the pregnancies of
      both their mothers and grandmothers enable familial cancer studies. FMC continues
      to collect samples, and surveillance of exposures or interventions like
      vaccination programs is feasible. In summary, the FMC is a unique, accessible
      biobank for epidemiological, biomarker, and surveillance studies on cancer.

PMID- 29071811
TI  - Top-down contextual knowledge guides visual attention in infancy.
AB  - The visual context in which an object or face resides can provide useful top-down
      information for guiding attention orienting, object recognition, and visual
      search. Although infants have demonstrated sensitivity to covariation in spatial
      arrays, it is presently unclear whether they can use rapidly acquired contextual
      knowledge to guide attention during visual search. In this eye-tracking
      experiment, 6- and 10-month-old infants searched for a target face hidden among
      colorful distracter shapes. Targets appeared in Old or New visual contexts,
      depending on whether the visual search arrays (defined by the spatial
      configuration, shape and color of component items in the search display) were
      repeated or newly generated throughout the experiment. Targets in Old contexts
      appeared in the same location within the same configuration, such that context
      covaried with target location. Both 6- and 10-month-olds successfully
      distinguished between Old and New contexts, exhibiting faster search times, fewer
      looks at distracters, and more anticipation of targets when contexts repeated.
      This initial demonstration of contextual cueing effects in infants indicates that
      they can use top-down information to facilitate orienting during memory-guided
      visual search.

PMID- 29071812
TI  - Cell-Free DNA in Oncology: Gearing up for Clinic.
AB  - In the past several years, interest in the clinical utility of cell-free DNA as a
      noninvasive cancer biomarker has grown rapidly. Success in the development of
      plasma genotyping assays and other liquid biopsy assays has widened the scope of
      cell-free DNA use in research and the clinic. Already approved by the US Food and
      Drug Administration in the narrow context of epidermal growth factor receptor
      mutated non-small cell lung cancer, plasma genotyping assays are currently being
      investigated in a wide array of clinical settings and modalities. These include
      plasma genotyping as a tool for early diagnosis, the detection of minimal
      residual disease, and the evaluation of treatment response/progression. In this
      review, we assess the clinical landscape of plasma genotyping assays and propose
      strategies for their further expansion into routine clinical care.

PMID- 29071813
TI  - Serum Macrophage Migration Inhibitory Factor as a Biomarker of Active Pulmonary
      Tuberculosis.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF), a pro-inflammatory
      cytokine with chemokine-like functions, has been shown to play a central role in
      several acute and chronic inflammatory diseases. However, limited information is
      available regarding the use of MIF as an inflammatory pathway marker in patients
      with tuberculosis. This study aimed to investigate the association of MIF with
      IFN-gamma and TNF-alpha in active pulmonary tuberculosis (APTB) following anti
      tuberculosis treatment. METHODS: The MIF, TNF-alpha, and IFN-gamma serum levels
      were determined in 47 patients with APTB by cytokine-specific ELISA at four
      phases: prior to anti-tuberculosis drug treatment (baseline), and following 2, 4,
      and 6 months of treatment. In addition, we measured the MIF, TNF-alpha, and IFN
      gamma serum levels in 50 health controls. RESULTS: MIF serum levels were
      significantly elevated (P<0.05) in patients with APTB prior to treatment compared
      with that in control subjects, and TNF-alpha >=449.7 pg/mL was associated with
      high MIF levels (>=13.1 ng/mL). MIF levels were significantly reduced (P<0.01)
      following 2, 4, and 6 months of treatment, with variations in TNF-alpha and IFN
      gamma serum levels. MIF levels were positively correlated with the paired TNF
      alpha level at baseline (r=0.1103, P=0.0316) and following 6 months of treatment
      (r=0.09569, P=0.0364). CONCLUSIONS: A reduction in the MIF serum levels in
      patients with APTB following anti-tuberculosis treatment may positively affect
      host immune protection against Mycobacterium tuberculosis infection. Thus, serum
      MIF levels may constitute a useful marker for assessing therapy effectiveness in
      patients with APTB.

PMID- 29071814
TI  - Extensively Drug-Resistant Escherichia coli Sequence Type 1642 Carrying an IncX3
      Plasmid Containing the blaKPC-2 Gene Associated with Transposon Tn4401a.
AB  - BACKGROUND: Extensively drug-resistant (XDR) Enterobacteriaceae carrying the
      bla(KPC) gene have emerged as a major global therapeutic concern. The purpose of
      this study was to analyze the complete sequences of plasmids from KPC-2
      carbapenemase-producing XDR Escherichia coli sequence type (ST) 1642 isolates.
      METHODS: We performed antimicrobial susceptibility testing, PCR, multilocus
      sequence typing (MLST), and whole-genome sequencing to characterize the plasmid
      mediated KPC-2-producing E. coli clinical isolates. RESULTS: The isolates were
      resistant to most available antibiotics, including meropenem, ampicillin,
      ceftriaxone, gentamicin, and ciprofloxacin, but susceptible to tigecycline and
      colistin. The isolates were identified as the rare ST1642 by MLST. The isolates
      carried four plasmids: the first 69-kb conjugative IncX3 plasmid harbors bla(KPC
      2) within a truncated Tn4401a transposon and bla(SHV-11) with duplicated
      conjugative elements. The second 142-kb plasmid with a multireplicon consisting
      of IncQ, IncFIA, and IncIB carries bla(TEM-1b) and two class 1 integrons. This
      plasmid also harbors a wide variety of additional antimicrobial resistance genes
      including aadA5, dfrA17, mph(A), sul1, tet(B), aac(3')-IId, strA, strB, and sul2.
      CONCLUSIONS: The complete sequence analysis of plasmids from an XDR E. coli
      strain related to persistent infection showed the coexistence of a bla(KPC-2)
      carrying IncX3-type plasmid and a class 1 integron-harboring multireplicon,
      suggesting its potential to cause outbreaks. Of additional clinical significance,
      the rare ST1642, identified in a cat, could constitute the source of human
      infection.

PMID- 29071815
TI  - Comparison of Singleplex Specific IgE Detection Immunoassays: ImmunoCAP Phadia
      250 and Immulite 2000 3gAllergy.
AB  - BACKGROUND: The identification of clinically meaningful specific immunoglobulin E
      (sIgE) is important for the diagnosis and management of allergic diseases.
      Various in vitro sIgE detection methods are available worldwide. Depending on the
      number of antigens that can be tested simultaneously, there are two
      representative methods: singleplex and multiplex. Singleplex sIgE detection is
      mainly provided by Thermo Fisher (ImmunoCAP) and Siemens (Immulite). This study
      aimed to compare the diagnostic agreement of two singleplex sIgE detection
      assays. METHODS: Sera from 209 Korean patients with allergic disease were used to
      compare the ImmunoCAP and Immulite assays with respect to the following
      allergens: inhalant allergens (Dermatophagoides farinae, cat and dog dander, oak,
      rye grass, mugwort, Alternaria, German cockroach) and food allergens (hen's egg
      white, cow's milk, wheat, peanut, soybean, and shrimp). Data from 902 paired
      comparison tests were included for comparisons. Qualitative, semi-quantitative,
      and quantitative comparisons were performed using statistical analyses. RESULTS:
      In qualitative comparisons, the positivity and negativity agreements ranged from
      75% (wheat, shrimp) to 96% (Alternaria). Class consistency (classes 0-6) was well
      matched. Spearman's rank correlation coefficients for all allergens except shrimp
      were over 0.7. In quantitative comparisons, all allergens excluding shrimp showed
      >0.7 intra-class correlation coefficients. CONCLUSIONS: The ImmunoCAP and
      Immulite systems showed similar performances. However, clinicians should consider
      fundamental methodological differences between the assays.

PMID- 29071817
TI  - Urinary YKL-40 as a Candidate Biomarker for Febrile Urinary Tract Infection in
      Young Children.
AB  - BACKGROUND: Given that YKL-40 is a known marker of inflammation, we sought to
      determine its association with urinary tract infection (UTI) in febrile children.
      METHODS: In total, 44 children aged 0 to 24 months with febrile UTI and 35 age-
      and sex-matched controls with fever from other causes were enrolled in the study.
      ELISA was performed to determine the level of YKL-40 in urine collected from each
      child. RESULTS: The ratio of urinary YKL-40 to creatinine (Cr) was higher in the
      children with a UTI than in the controls (P<0.001). The area under the ROC curve
      for detecting UTI was 0.88 for the urinary YKL-40/Cr ratio, 0.86 for pyuria, and
      0.71 for positive nitrite on urinalysis. We applied a cut-off value of 125.23
      pg/mg to urinary YKL-40/Cr for detecting UTI. Eight of nine children in the
      control group with pyuria had urinary YKL-40/Cr levels lower than 125.23 pg/mg,
      and the one child in the UTI group without pyuria or positive nitrite had a
      urinary YKL-40/Cr level greater than 125.23 pg/mg. CONCLUSIONS: Determining the
      levels of urinary YKL-40/Cr may help identify true cases of UTI in febrile young
      children, especially when they have pyuria but not nitrite, or have neither
      pyuria nor nitrite in the urine.

PMID- 29071818
TI  - Evaluation of Allplex Respiratory Panel 1/2/3 Multiplex Real-Time PCR Assays for
      the Detection of Respiratory Viruses with Influenza A Virus subtyping.
AB  - The Allplex Respiratory Panel 1/2/3 (All16) is a multiplex PCR assay for
      detecting 16 respiratory viruses with influenza A virus (FluA) subtyping, and the
      first clinical assay based on multiple detection temperatures. We compared the
      results between All16 and Anyplex II RV16 (Any16) in 426 clinical samples.
      Samples showing discrepancies between the two tests were further tested using
      monoplex PCR. FluA subtyping based on the hemagglutinin type results of All16,
      which yielded H1, H3, and non-H1/H3, was compared with the results of the BioFire
      FilmArray respiratory panel. The positive and negative percent agreements and
      kappa value for each virus between All16 and Any16 ranged from 54.5-100.0%, 84.7
      100.0%, and 0.57-1.00, respectively. FluA subtype results from All16 for 26
      samples were consistent with those from FilmArray. Good agreement was observed
      between the two methods, except when analyzing human enterovirus (kappa value
      0.70), and the All16 showed reliable FluA subtyping results. For parainfluenza
      virus 3, the All16 was more sensitive than Any16. When testing 28 samples
      simultaneously, the mean test time and hands-on time were 4.3 and 0.5 hours,
      respectively in All16. In conclusion, All16 showed reliable performance, but
      further studies are needed regarding human enterovirus analysis.

PMID- 29071816
TI  - Application of Multiplex Ligation-Dependent Probe Amplification Assay for
      Genotyping Major Blood Group Systems Including DEL Variants in the D-Negative
      Korean Population.
AB  - BACKGROUND: The DEL blood type, a very weak D variant, is a major concern in the
      field of transfusion medicine because of its potential to cause anti-D
      alloimmunization. We investigated the molecular basis of serologically D-negative
      phenotypes, including the DEL type, and the distribution of other blood group
      systems in the Korean population using the recently developed multiplex ligation
      dependent probe amplification (MLPA) assay. METHODS: Blood group genotyping using
      the MLPA assay and RhCE phenotyping were performed on randomly selected 95 D
      negative red blood cell products. The MLPA results were verified by multiplex PCR
      for the RHD promoter, exons 4, 7, and 10 and by direct sequencing of RHD exon 9.
      RESULTS: Out of 95 cases, total deletion of the RHD was observed in 74 cases
      (77.9%) and four cases (4.2%) had an RHD-CE-D hybrid allele. The other 17 cases
      (17.9%) had an RHD(1227G>A) allele, which was further confirmed by sequencing
      analysis. The RhCE phenotypes of RHD(1227G>A) alleles were composed of 14 Cce and
      3 CcEe, and all 60 cases of the ce phenotype were revealed to have a total
      deletion of the RHD. Genotyping results and allele distribution of the other 17
      blood group systems were consistent with previous reports on the East Asian
      population. CONCLUSIONS: MLPA assay correctly determined RHD genotype, including
      RHD-CE-D hybrid alleles or RHD(1227G>A) allele, and other clinically relevant
      blood group genotypes in D-negative Koreans. The use of MLPA assay on
      serologically D-negative individuals may help improve transfusion safety by
      preventing anti-D alloimmunization.

PMID- 29071819
TI  - Is It Necessary to Repeat Fecal Occult Blood Tests with Borderline Results for
      Colorectal Cancer Screening?
AB  - The fecal immunochemical test (FIT) is the initial non-invasive investigation of
      choice for population-based colorectal cancer (CRC) screening. We evaluated the
      positivity rate in repeated tests using the same fecal specimen that showed
      borderline results in the FIT. A total of 6,465 patients were tested with the FIT
      in a tertiary-care hospital from July to December 2016. FIT was done using OC
      Sensor PLEDIA (Eiken Chemical Co., Tokyo, Japan). Among 6,465 patients, 364
      (5.6%) patients showed a positive FIT result of over 20 MUg Hb/g feces. A total
      of 112 (1.7%) patients showed borderline scores of 10.2-20 MUg Hb/g feces, and
      5,989 (92.6%) patients showed negative results of less than 10 MUg Hb/g feces.
      Among the 101 repeat-tested patients, 19 (18.8%) of the patients' scores
      converted to levels above the positive cut-off threshold. Repeated results of 19
      patients showed score elevations from 20.2 to 68 MUg Hb/g feces. These results
      suggest that it is most important to analyze properly prepared samples, even if
      only once. Therefore, the laboratory staff should ensure the proper preparation
      of stool specimens for FIT. Laboratory directors should choose the best cut-off
      value for detecting CRC at their respective institutions.

PMID- 29071820
TI  - Application of Multigene Panel Sequencing in Patients with Prolonged Rate
      corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and
      SCN5A.
AB  - Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a
      prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic
      causes in patients with prolonged QTc intervals who were negative for pathogenic
      variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular
      genetic testing was performed using a panel including 13 LQTS-related genes and
      67 additional genes implicated in other cardiac diseases. Overall, putative
      genetic causes of prolonged QTc interval were identified in three of the 30
      patients (10%). Among the LQTS-related genes, we detected a previously reported
      pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy
      syndrome. Among the genes related to other cardiac diseases, a likely pathogenic
      variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic
      polymorphic ventricular tachycardia. Another patient who developed dilated
      cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic
      variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy.
      Comprehensive screening of genetic variants using multigene panel sequencing
      enables detection of genetic variants with a possible involvement in QTc interval
      prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

PMID- 29071822
TI  - Molecular and Cytogenetic Studies in a Child with Burkitt Lymphoma and Ataxia
      Telangiectasia Syndrome Harboring MYC Overexpression and Partial Trisomy 8.

PMID- 29071821
TI  - Chinese Pediatric Reference Intervals for Serum Cortisol on IMMULITE 2000.
AB  - Clinical interpretation of the test results for cortisol based on continuous
      reference intervals with appropriate partitions improves pediatric diagnosis;
      however, these values are available only for Caucasians. To develop the pediatric
      reference intervals for Chinese population, we examined the serum cortisol levels
      in 1,143 healthy Chinese children aged 4-18 years (566 boys and 577 girls), using
      an IMMULITE 2000 Immunoassay System (Siemens Healthcare GmbH). Phlebotomy was
      performed at 7-9 a.m. for 284 boys and 287 girls and at 1-3 p.m. for the others.
      They were divided into four age groups according to the Clinical and Laboratory
      Standards Institute guideline EP28-A3c, with the last group further stratified
      according to sampling time. Separate reference intervals of 49.6-323.7, 70.9
      395.3, and 90.1-448.7 nmol/L were established for children aged 4-8, 9-12, and 13
      15 years, respectively. Further, reference intervals of 118.2-464.7 and 71.4
      446.7 nmol/L were established for morning and afternoon cortisol levels,
      respectively, in children aged 16-18 years. Further studies are necessary to
      transfer and validate these reference intervals in other analytical systems and
      pediatric populations, and to allow for broader applications.

PMID- 29071823
TI  - Effect of Accreditation on the Accuracy of Diagnostic Hematologic Tests: Standard
      Deviation Index Analysis.

PMID- 29071824
TI  - Polymicrobial Anaerobic Bacteremia Caused by Butyricimonas virosa and Brachyspira
      pilosicoli in a Patient with Peritonitis following Intestinal Perforation.

PMID- 29071825
TI  - A Case of Anti-reticulin Antibody-positivity in Metachronous Double Primary
      Cancer.

PMID- 29071826
TI  - Deletion of 20p13 and Duplication of 20p13p12.3 in a Patient with Delayed Speech
      and Development.

PMID- 29071827
TI  - Identification of Homozygous Likely Pathogenic Variant of ALDH3A2 in a Korean Boy
      with Sjogren-Larsson Syndrome.

PMID- 29071828
TI  - Intactness of Medical Nonsterile Gloves on Use of Alcohol Disinfectants.

PMID- 29071829
TI  - ?

PMID- 29071830
TI  - [Hormonal treatments and venous thrombosis in women].
AB  - Venous thromboembolism is frequently associated with hormonal factors in women. A
      thorough medical history taking of vascular risks and an individual evaluation of
      the risk-benefit ratio should precede any prescription of hormonal therapies. In
      contrary to progestin-only-pills, estroprogestative contraceptives increase 3-6
      times the risk of venous thrombosis. In assisted reproductive techniques, venous
      thrombosis is frequently associated with the occurrence of a severe ovarian
      hyperstimulation syndrome. Antagonist ovarian stimulation protocols lower the
      risk of hyperstimulation and should therefore be preferred. Finally, at
      menopause, hormonal treatments combining transdermal estradiol and micronized
      progesterone do not seem to increment the risk of thrombosis.

PMID- 29071831
TI  - [Screening in onco-gynecology : beneficial for all patients ?]
AB  - Every day, 5 women are diagnosed with gynecological cancer in Switzerland.
      Prognosis of ovarian, endometrial and cervical cancer is dependent on early
      diagnosis. Cervical cancer mortality has decreased since the introduction of
      screening. Unfortunately, screening in ovarian and endometrial cancer has not
      shown the same results. On the contrary, patients screened for these cancers have
      an increased morbidity without any additional benefit of survival. This article
      presents a review of the clinical benefits and harms of gynecological cancer
      screening.

PMID- 29071832
TI  - [Assisted reproductive technology : strategies of elective single embryo
      transfer].
AB  - The development of assisted reproductive technology (ART) has led to the birth of
      nearly 6 million children since the first IVF baby in 1978. For many years, it
      was routine practice to transfer multiple embryos in order to obtain the highest
      pregnancy rates. This strategy has induced a dramatic increase in multiple
      pregnancies and the associated complications for the mother and the child.
      Following better awareness of these issues, ART specialists have tried to reduce
      multiple pregnancy rates with the goal of producing a single, healthy full term
      baby. Improvement in embryo culture and cryopreservation are the key factors
      leading to the strategy of elective single embryo transfer (eSET) which
      represents the best option to achieving this goal. However eSET strategy needs to
      be implemented in good prognosis patient with good quality embryos.

PMID- 29071833
TI  - [Amenorrhea in athletic adolescents : the tip of the iceberg].
AB  - The female athletic triad refers to the interaction between menstrual function,
      energy availability and bone density. When an imbalance appears between energy
      input and output, the global health of the athletic teenager is at risk of
      somatic and/or psychological complications as defined by the RED-S (Relative
      Energy Deficiency in Sports). In athletic girls menstrual disorder should be seen
      as an alert. It may be difficult to distinguish it from menstrual irregularity
      due to immature hypothalamic-hyphophysic-gonadal axis, which can be physiological
      at that age. A multidisciplinary approach is needed. The challenge is to find a
      balance between sport practice and prevention of complications due to lack of
      estrogens.

PMID- 29071834
TI  - [Out-of-hospital delivery : present state and perspectives].
AB  - Out-of-hospital delivery is rare in Switzerland and it accounted for 2,5 % of all
      the births in 2015. In Switzerland, out-of-hospital childbirth is not subject to
      any official regulations. It takes place mainly in midwifery units (1,6 %) and at
      home (0,9 %), by independent midwifes. One in six women needs to be transferred
      to a hospital because of complications. Perinatal mortality is higher in out-of
      hospital childbirth and the hospital is the safest place to give birth. The level
      of intervention may be lower, maybe because the women choosing to give birth in
      alternative settings are at lower risk.

PMID- 29071835
TI  - [Evolution of cesarean section rates according to Robson classification in a
      swiss maternity hospital].
AB  - We conducted a retrospective study was conducted in the Centre Hospitalier
      Universitaire Vaudois (CHUV) including all births between the 1st January 1997
      and 31st December 2011 to analyze the cesarean section (CS) rate using the
      different groups of the Robson classification in a Swiss maternity hospital. The
      overall CS rate was 29 %, mainly related to group 5 (multiparous with previous
      CS) and group 2 (nulliparous women induced or who had CS before labor). The study
      also shows that induction of labor on maternal request in nulliparous at term
      (group 2a) increased significantly the risk of CS compared to induction of labor
      for medical reason (p<0.001). The Robson classification system appears as a
      simple tool for monitoring CS rates. The main strategies for reducing CS rates
      will be through better selection of women for VBAC (vaginal birth after
      caesarean) and limitation of induction of labor, especially in nulliparous women.

PMID- 29071837
TI  - ?

PMID- 29071836
TI  - ?

PMID- 29071838
TI  - ?

PMID- 29071840
TI  - ?

PMID- 29071839
TI  - ?

PMID- 29071841
TI  - ?

PMID- 29071842
TI  - [Literature study on prevention and treatment of community acquired pneumonia by
      traditional Chinese medicine].
AB  - Among the literatures of the prevention and treatment of community-acquired
      pneumonia (CAP) published in recent years, there were 16 kinds of classic
      prescription, including 52 RCTs about Maxingshigan Decoction, 21Chinese patent
      medicines. There are eight kinds of indications for the drug specification, among
      which the literatures of Tan Reqing injection accounted for the most about 136
      RCTs; There were literatures about non-drug treatment, including: acupuncture,
      Chinese medicine paste, enema, Chinese medicine ionization, Chinese medicine
      fumigation, bamboo cans and so on. In this study, author has analysed the classic
      prescription, Chinese patent medicine and non-drug therapy referring to
      advantages and disadvantages of CAP, which could be used to treat virus infection
      instead of antibiotic therapy. Based on antibiotic therapy, Chinese medicine
      treatment could increase synergistic interaction while decrease the antibiotic
      side-effects. In addition, Chinese medicine could perform synergistic interaction
      in CAP every period, which resulted from classified analysis of basic studies
      about Chinese medicine treatment in CPA. This study is aimed to provides an
      important basis for clarifying the direction of scientific research.

PMID- 29071843
TI  - [Research progress of traditional Chinese medicine in prevention and treatment of
      sepsis].
AB  - Sepsis brings great burden to the industry of health care and national economy,
      and antibiotics used in anti-infective treatment will cause the emergence of drug
      resistant bacteria, adverse reactions, and reduce the efficacy and quality of
      life. However, with the deepening of the study of traditional Chinese medicine
      treatment of sepsis, in reducing the production of drug-resistant bacteria,
      changing the drug resistance of drug-resistant bacteria, preventing multiple
      infection, response to inflammatory response and immune damage, treatment of
      gastrointestinal dysfunction and coagulation disorders, TCM is gradually exerting
      its advantages. In recent years, with the continuous development of clinical
      research, the curative effect of traditional Chinese medical way is widely
      recognized, especially Xuebijing injection. In addition, the clinical research of
      Chinese medicine, acupuncture, acupoint sticking is more and more. Its play an
      important role to reduce the mortality of patients with sepsis, reduce
      inflammatory indexes, blood coagulation index. However, the pathophysiology of
      sepsis is not clear, the illness progress rapidly and the problem of drug
      resistant bacteria resistant, our task is still arduous. Looking forward to the
      emergence of higher quality research, and looking forward to more individualized
      and refined treatment programs.

PMID- 29071844
TI  - [Advantages and evidence of Chinese medicine in prevention and treatment of adult
      acute tonsillitis].
AB  - Though evaluation and analysis on the relevant literatures at home and abroad in
      recent years, the total number of retrieved literature was 2 664. According to
      the inclusion criteria and exclusion criteria,the literatures were screened out,
      and the results were as follows:374 literatures. To analyse the advantages and
      evidence of Chinese medicine in the prevention and treatment of adult acute
      tonsillitis. It is found to be effective, convenient and practical for the
      treatment of acute tonsillitis by traditional Chinese medicine (TCM) like
      treatment according to syndrome differentiation, Chinese patent drug, self
      Chinese medicine prescription and external treatment. TCM has obvious advantages
      in the prevention and treatment of acute tonsillitis, has the function of
      supplementing or substituting antibiotics, and has the function of regulating the
      defense function of organism.

PMID- 29071845
TI  - [Review on advantages and evidence of treating and preventing urinary tract
      infection in traditional Chinese medicine].
AB  - Urinary tract infection (UTI) in traditional Chinese medicine (TCM) belongs to
      the category of stranguria. This article describes the unsatisfactory situations
      in clinical practice such as antibiotics abuse, increasing of drug-resistant
      bacteria, high recurrence rate, etc. According to evidence-based medicine,
      literatures as evidence are collected for summarizing and analyzing and the
      result shows the advantages of TCM of relieving symptoms, reducing the dosage of
      antibiotics, less side effects, lower recurrence rate, etc. In the field of
      fundamental research, literatures associated with UTI are also summarized and
      analysed from several perspectives, such as causes, pathogenesis, syndrome
      differentiation, pharmacological effects of Chinese herbal medicine, working
      mechanism of non-drug therapy, etc and the result presents that integrated
      treatment of TCM in UTI has significant advangtages and its own characteristic.

PMID- 29071846
TI  - [Advantages and evidences research on Chinese medicine for treatment of pelvic
      inflammatory disease].
AB  - Pelvic inflammatory disease is an infectious disease. At present, Western
      medicine is mainly treated with antibiotics. However, the situation of
      antibiotics abuse is so grim that the potential risks such as the imbalance of
      bacteria, the resistance of bacteria, the production of super bacteria and the
      increase of adverse reactions are becoming more and more serious. Therefore, it
      is urgent to find a way to supplement or substitute antibiotics for the treatment
      of this disease. Traditional Chinese medicine treatment of the disease is
      effective and has its unique advantages. This paper mainly discusses the
      advantages and evidences of traditional Chinese medicine (TCM) treatment of
      pelvic inflammatory disease, to further prove the effectiveness and safety of TCM
      treatment and to provide medical evidence of reducing antibiotics use.

PMID- 29071847
TI  - [A commentary of literature research of traditional Chinese medicine for acute
      upper respiratory tract infection in children].
AB  - Acute upper respiratory tract infection is the most common infectious disease in
      children's respiratory system. The pathogen to the main virus, can account for
      more than 90% of the primary upper respiratory tract infectio. However, there is
      no specific anti-viral drugs specifically for the disease, in addition to the
      existence of excessive, widespread use or even abuse of antibiotics.Long-term
      clinical practice has confirmed that Chinese medicine is safe and effective in
      treating acute upper respiratory tract infection in children. The author reviews
      the literatures of multiple databases, and analyzes the advantages of Chinese
      patent medicine in the treatment of acute upper respiratory tract infection in
      children from the perspective of clinical research and experimental basic
      research. It also puts forward the existing problems and possible research
      directions of Chinese patent medicine in the treatment of acute upper respiratory
      tract infection in children.

PMID- 29071848
TI  - [Study of Jinye Baidu granule in treatment of wind-warmth lung heat disease (heat
      in lung-wei pattern): a randomized, double-blind, parallel-controlled trial].
AB  - A randomized, double-blind, active parallel controlled trial will be conducted to
      include patients with acute upper respiratory infection and wind-warmth lung heat
      disease (heat in lung-wei pattern). Patients with serious bacterial infection
      (white blood cell count>1.2*1010, neutrophil>80%) will be excluded.so as to
      further identify Jinye Baidu Granule indications of Wind-warmth lung heat disease
      (heat in lung-wei pattern).According to the subjects of symptoms of fever and
      sore throats,Patients will be divided into three blocks: fever, swelling and sore
      throat, combined fever and swelling and sore throat. Subjects in three blocks
      will be divided into treatment group and control group with stratified blocked
      randomization. The treatment group will be treated with Jinye Baidu Granule, and
      the control group will be treated with Fufang Shuanghua granule. Primary outcome
      measure of patients with fever will be body temperature recovery time. Primary
      outcome measure of patients with swelling and sore throat will be throat symptom
      score. Primary outcome measures of patients combined with fever and swelling and
      sore throat will be body temperature recovery time and throat symptom score.
      Before and after all of the patients in the group were collected blood and urine
      routine, liver and renal function, electrocardiogram (ECG) data as the safety
      index while observing it adverse events. A total of 623 patients were included.
      Compared with control group,sore throat symptoms of patients with sore throat and
      pharyngeal symptoms total score have significantly different. so Jinny Baidu
      granule have a significant advantage in the treatment of sore throat. All of the
      experiments showed that the safety of the drug was good. Nausea, vomiting,
      stomach pain, diarrhea, digestive tract symptoms may occur only occasionally. We
      should pay attention to the changes when using in patients with spleen deficiency
      cold to avoid adverse reaction.

PMID- 29071849
TI  - [Efficacy and safety of Lianhua Qingwen capsule for influenza: a systematic
      review].
AB  - To evaluate the efficacy and safety of Lianhua Qingwen capsule for influenza. All
      reports of the randomized controlled trials (RCTs) on Lianhua Qingwen capsule
      treating influenza were retrieved from database of CNKI, WANFANG DATA, VIP,
      PubMed, the Cochrane Library by February 2017. The studies were screened
      according to the inclusion and exclusion criteria, the data were extracted by 2
      authors, the quality of the included RCTs was assessed, and meta-analysis was
      performed using Revman5.3 software. A total of 1 525 patients and 10 studies were
      included. The results of meta analysis showed that compared with oseltamivir,
      Lianhua Qingwen capsule was more effective in alleviating flu symptoms, including
      the time of headaches disappeared [SMD=-0.25,95% CI(-0.48, -0.01)], the time of
      sore throat disappeared [SMD=-0.53,95% CI(-0.72, -0.34)], the time of cough
      disappeared [SMD=-0.39,95%CI(-0.57, -0.21)], whole body aches disappeared [ SMD=
      0.49, 95% CI (-0.78, -0.21)], the time of weak disappeared [SMD=-0.56,95%CI (
      0.82, -0.29)], and the time of abatement of fever [SMD=-3.47,95%CI(-6.27, 
      0.67)]. Also, there were some statistical significant differences between the two
      groups except nasal congestion and the time of virus turning negative. Compared
      with Ribavirin, Lianhua Qingwen capsule was more effective in terms of the rate
      of temperature effect, [RR=1.53, 95% CI (1.24, 1.90)], the difference between the
      two groups was statistically significant. Compared with Ankahuangmin capsules,
      significant differences were found in terms of the he rate temperature effect
      [RR=1.37, 95%CI (1.19,1.57)]. Current evidence shows that Lianhua Qingwen capsule
      is more effective and safer than Oseltamivir, Ribavirin and Ankahuangmin
      capsules. Due to the low quality of the clinical research, the accuracy of this
      conclusion needs to be conducted to verify.

PMID- 29071850
TI  - [Systematic review of effectiveness and safety of pudilan Xiaoyan oral liquid in
      treating pediatric suppurative tonsilitis].
AB  - The review aims to assess the effectiveness and safety Pudilan Xiaoyan oral
      liquid in treating pediatric suppurative tonsillitis systematically through
      searching relevant electronic database and collecting relevant literature. Meta
      analysis was performed with the RevMan 5.3 software. Eighteen RCTs of 1 883
      patients of pediatric suppurative tonsillitis were included. Meta-analysis showed
      that: compared with the application of antibiotics alone, combined with Pudilan
      can effectively improve the treatment of pediatric suppurative tonsillitis in
      efficacy rate and shorten the time of recovering normal temperature, the time of
      tonsil purulent discharge and can also reduce the extinction time of sore throat,
      antiadoncus or congestion subsided and appetite recovery. There was no severe
      adverse reaction during the treatment. Compared with the application of
      antibiotics alone, combined with Pudilan may be more effective and safe in the
      treatment of pediatric suppurative tonsillitis, which can not be strongly proved
      at present for lack of studies with high quality.

PMID- 29071851
TI  - [Lanqin oral liquid for the treatment of chronic pharyngitis:systematic review
      and Meta-analysis of randomized clinical trials].
AB  - To systematically assess the effectiveness and safety of lanqin oral liquid for
      the treatment of chronic pharyngitis. Databases including PubMed, Embase, The
      Cochrane Library, SinoMed, CNKI, VIP and Wanfang Data were electronically
      searched in March 2017 for randomized controlled trials(RCTs) on Lanqin oral
      liquid for the treatment of chronic pharyngitis. Two authors independently
      screened literature, extracted data, and assessed the risk of bias of included
      studies. Then, meta-analysis was performed by RevMan 5.3 software. Thirteen RCTs
      were included with a total of 1 642 patients. The results of meta-analysis showed
      that the efficiency of lanqin oral liquid were significantly higher than those of
      conventional therapy or other treatments; Besides, lanqin oral liquid could
      significantly increase the amount of IL-2 further more, lanqin oral liquid could
      significantly reduce the amount of TNF-alpha. Safety of lanqin oral liquid was
      not concerned by any RCT. Current evidence indicates that the efficiency of
      lanqin oral liquid was better than conventional therapy or other treatments. Due
      to the poor quality of the included studies, the above conclusion should be
      verified by more RCTs of high quality.

PMID- 29071852
TI  - [Huoxiang Zhengqi formulas for treatment of gastrointestinal type cold:a
      systematic review and Meta-analysis].
AB  - This systematic review aims to evaluate the efficacy and safety of Huoxiang
      Zhengqi formulas in treating gastrointestinal type cold. Seven electronic
      databases,including CNKI, WanFang Data, Vip, SinoMed, PubMed, Cochrane Library,
      Embase will be searched from the inception of the study until March 2017.All
      randomized controlled trials that evaluate the treatment of Huoxiang Zhengqi
      formulas for gastrointestinal type cold will be eligible. The methodological
      quality will be assessed using the Cochrane risk of bias tool for randomized
      clinical trials and Review Manager 5.3 software is used for analyzing the
      data.The results are: eight RCTs and 680 patients are included .Meta-analysis are
      performed according to the stratification of the treatment strategy. Eight
      studies report clinical efficacy, among them four studies show Huoxiang Zhengqi
      formulas are better than western medicine(RR and 95%,1.2[1.08, 1.33]), another
      four studies showHuoxiang Zhengqi formulas in conjunction with conventional
      treatment are better than conventional treatment(RR and 95%,
      1.32[1.20,1.46]).About symptom remission rate, one study shows the treatment
      group effect is better than the control group from the following clinical
      symptoms:chills,fever,bowel diarrhea,the effect of treating sore throat itchy is
      same with western medicine treatment.No adverse reactions are found about
      Huoxiang Zhengqi formulas in this study.Current evidence shows that
      Huoxiangzhengqi formulas are better than Western medicine group and western
      medicine routine treatment group from clinical efficacy. Limited by the quantity
      and quality of studies, more large-scale and rigorously designed randomised
      controlled trials with large sample size are warranted to clarify the
      conclusions.

PMID- 29071853
TI  - [Guizhi Fuling capsule / pill treatment for chronic pelvic inflammatory disease:a
      systematic review of randomized clinical trials].
AB  - This systematic review aims to systematically evaluate the efficacy and safety of
      Guizhi Fuling Capsule/Pill on the treatment of chronic pelvic inflammatory
      disease. We searched CNKI datebases,WanFang,SinoMed,PubMed,Embase,The Cochrane
      Library from the inception to February 2017,to collect randomized controlled
      trials(RCTs)of Guizhi Fuling Capsule/Pill in treating chronic pelvic inflammation
      disease.Two reviewers independently screened literature,extracted date and
      assessed the risk of bias of included studies.Then,the risk assessment of
      included references was evaluated according to criteria recommended by Cochrane
      Handbook 5.3.A total of 30 RCTs involving 3 586 patients were finally included.30
      studies reported the clinical efficacy,the result of meta-analysis showed
      that:compared with the western medicine group,Guizhi Fuling (capsule,pill)
      combined with western medicine could significantly improve the clinical efficacy
      [RR=1.20,95%CI(1.16,1.23)];3 studies reported recurrence rate,the result of meta
      analysis showed that:compared with the western medicine,Guizhi Fuling
      (capsule,pill) combined with western medicine could decrease the recurrence rate
      [RR=0.33,95%CI(0.18,0.62)]; Their secondary indicators mainly included hs-CRP,
      plasma viscosity ratio and tumor necrosis factor and fibrin,the result of meta
      analysis showed that: Guizhi Fuling (capsule,pill) combined with western medicine
      was better than western medicine in terms of anti-inflammatory and improving
      blood circulation.17 studies reported adverse reactions,most of the adverse
      events were the irritation of gastrointestinal tract. The result showed that:
      compared with the western medicine group, the incidence of adverse reactions in
      Guizhi Fuling (capsule,pill) combined with western medicine group is low.Guizhi
      Fuling(capsule,pill) did not increase the adverse reactions. The available
      evidence suggests that: Guizhi Fuling(capsule, pill) compared with the western
      medicine group, Guizhi Fuling (capsule,pill) combined with western medicine was
      more effective than the western medicine group in terms of clinical efficacy,
      recurrence rate, anti-inflammatory and plasma viscosity.Due to the limited
      quality and quantity of included studies,more high quality RCTs are needed to
      verify the above conciusion.

PMID- 29071855
TI  - [Analysis of reporting specification about sepsis practice guideline based on
      RIGHT standard].
AB  - At present, the study of clinical practice guide focuses on the quality of the
      guide, but not enough attention to the reporting standards of the practice guide,
      so how to standardize the report is an urgent problem in the field of evidence
      based medicine. This paper uses the latest practice guidance reporting tool RIGHT
      standard, analyzes the latest two sepsis practice guidelines at home and abroad,
      and found that there are few problems in the basic information, recommendations
      and other information in 7 major areas, and many deficiencies in background,
      evidence, review and quality assurance, funding and declaration and management of
      interests, in particular, domestic guidance. We hope that the researchers will
      use the RIGHT standard to develop new guidelines for sepsis or other areas,
      standardize the report of the guide, especially the writing of traditional
      Chinese medicine guide, should reflect the characteristics of traditional Chinese
      medicine.

PMID- 29071854
TI  - [Interpretation of chinese clinical guidelines for acute upper respiratory tract
      infection in children].
AB  - Acute upper respiratory tract infection(AURI) in pediatrics is the most common
      disease in children, often caused by a variety of pathogens. The incidence of
      clinic patients accounts for over 60%. The domestic organizations and institutes
      have issued 5 agnostic and therapeutic clinical guidelines about AURI in
      children. This article briefly reviewed and interpreted the contents and
      qualities of the relevant guidelines. There are fewer problems with them,such us
      smaller quantities, lower quality, slower update. The future of Chinese medicine
      against AURI in children was discussed in the end.

PMID- 29071856
TI  - [A study on exploring consensus developing standards in clinical practice
      guideline for traditional Chinese medicine].
AB  - It is a compulsory step from expert consensus to recommendation in developing
      clinical practice guideline. Therefore, it is necessary to establish standards
      for structuring expert consensus developing process by integrating traditional
      Chinese medicine theories into evidence. We summarized our experience to put
      forward to forming a flowchart and transparency process for making recommendation
      considering both evidence and traditional theories from traditional Chinese
      medicine in making clinical guideline. It is hoped that this could be useful for
      future researchers in this area.

PMID- 29071857
TI  - [Overall intestinal permeability of multiple components in lotus leaf by in situ
      single pass intestinal perfusion models].
AB  - To investigate the overall intestinal permeability of multiple components in
      lotus leaves and make clear the interaction in composition absorption process.
      Rat single-pass intestinal perfusion technique was used, and the results showed
      that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin,
      kaempferol from lotus leaf were greater than 0.5*10-4 cm*s-1. In the
      biopharmaceutics classification system (BCS) intestinal permeability property,
      these ingredients were high permeable components, while the hyperin was low
      permeable component. However, in the multi-component environment of the lotus
      leaf extract, component permeation was changed. Semi quantitative analysis of the
      unclear components showed that under the multi-component environment, four in
      seven components with relatively high contents had a Peff value less than 0.5*10
      4 cm*s-1, indicating these 4 components were of low permeability, while other 3
      components were of high permeability. The results could be valuable to make clear
      the overall intestinal permeability of multiple components in lotus leaf, and lay
      a foundation for studying the mechanism of the lipid-lowering effect of lotus
      leaf.

PMID- 29071858
TI  - [Intestinal absorption and metabolism of Puerariae Lobatae Radix decoction by in
      situ closed-loop method].
AB  - Biopharmaceutics classification system of Chinese materia medica (CMMBCS)
      emphasizes characteristic of the multi-component environment based on the drug
      solubility and permeability. In this study, the in situ closed-loop method
      combined with LC-MS technique was utilized to study the intestinal absorption and
      metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis
      for intestinal permeability components in CMMBCS. A total of 36 components were
      identified from PLRD. Among them, 17 components could be detected in the plasma
      sample, indicating that 17 components could be absorbed into blood, so these 17
      components could be used as intestinal permeability evaluation components in
      CMMBCS. The other 19 components were not detected in the plasma sample,
      suggesting that they may not be absorbed or metabolized by the gut wall enzymes.

PMID- 29071859
TI  - [Validation of in situ single pass perfusion model based on P-gp].
AB  - To validate in situ rats intestinal single pass perfusion model based on P
      glycoprotein (P-gp). Firstly, phenol red perfusion was carried out to verify the
      close connection structure of intestinal epithelial cells, and the integrity of
      the intestinal epithelium, with a gravimetric method for correcting water flux.
      The level of phenol red was determined by high performance liquid chromatography
      (HPLC) both before and after perfusion. Secondly, the positive drug digoxin
      specified by FDA was used to validate the model. After different mass
      concentrations of verapamil were given in the rats, the absorption parameters of
      digoxin in ileum of rats were observed and compared. The results showed that the
      phenol red was absorbed in rats ileum segment, with an effective permeability
      coefficient of (1.09+/-0.62)*10 -6 cm*s -1. The experiment results indicated that
      the close connection structure of intestinal epithelial cells was normal, and the
      integrity of the intestinal epithelium was maintained well. In digoxin perfusion
      experiment, in case no verapamil was given, digoxin showed certain degree of
      absorption in rat ileum, with an effective permeability coefficient (Peff) of
      (1.07+/-0.59)*10 -5 cm*s -1; after mass concentrations of 0.01,0.1 mmol*L -1
      verapamil were given, the absorption of digoxin was on the rise in rat ileum,
      with an effective permeability coefficient Peff of (1.58+/-0.69)*10 -5, (3.28+/
      0.95)*10 -5 cm*s -1 respectively (P<0.05). Digoxin perfusion experiment verified
      that P-gp expression in small intestine epithelium was intact and can be used in
      the research of P-gp efflux transporter.

PMID- 29071860
TI  - [Biopharmaceutics classification system of Chinese materia medica of berberine in
      Gegen Qinlian decoction].
AB  - One of the top-level researches of biopharmaceutics classification system of
      Chinese materia medica (CMMBCS) is the study on single component in compound
      Chinese medicine. The medicines shall be classified according to its solubility
      and intestinal permeability, as well as the ascending degree in multicomponent
      environment. Based on above, we chose berberine as the main object to explore the
      change rules of its solubility and intestinal permeability in Gegen Qinlian
      decoction. Shaking flask-HPLC was used to detect the solubility changes of
      berberine in compounds. The qualitative investigation of berberine in intestinal
      absorption was measured by everted gut sac, and the quantitative research of
      berberine in intestinal absorption was measured by single-pass intestinal
      perfusion experiment, while the qualitative and quantitative research of
      berberine absorption into blood was measured by in intestinal perfusion with
      venous sampling experiment.

PMID- 29071861
TI  - [In vitro and in vivo intestinal absorption of Huanglian decoction in multi
      component environment].
AB  - The effect of drugs in the body is always inseparable with the dynamic processes
      of absorption, distribution, metabolism and excretion. For oral drug, absorption,
      as the first link to enter the body, is particularly valued. Traditional Chinese
      medicine has multiple components and multiple targets, and the nature of its
      single composition is different from that in the multicomponent environment.
      Alkaloids in Huanglian extract was used as the main object in this study to
      establish an analytical method for determining the content of alkaloids in
      Huanglian. In addition, the compositions of the Huanglian aqueous extract
      solution which can be absorbed through intestinal wall into blood, were initially
      determined by the means of everted gut sac and in intestinal perfusion with
      venous sampling experiment. This paper can provide data reference and support for
      the further study on the absorption and metabolism of Huanglian.

PMID- 29071862
TI  - [Review on anxiolytic effect of natural small-molecule phenols].
AB  - Phenolic compounds have multiple bioactivities, such as anti-oxidant, anti-tumor,
      anti-bacterial, and anti-inflammatory activities. Recent literatures have
      demonstrated that flavonoids have a significant anti-anxiety effect on the
      central nervous system. In addition, studies showed that flavonoids acted as pro
      drugs, which were transformed into smaller phenols through intestinal microflora.
      The small phenolic metabolites were crucial for the anxiolytic effects of these
      flavonoids, indicating that natural small-molecule phenols(NSMP) generally have
      anxiolytic activities. In this paper, the supporting evidences (before June 2016)
      from SciFinder database have been summarized. Furthermore, NSMPs were classified
      according to chemical structures; their anxiolytic effects, mechanisms, and the
      structure-activity relationships were also discussed.

PMID- 29071863
TI  - [Secondary metabolic responses to treatment of 2-aminoindan-2-phosphonic acid in
      cell lines from Arnebia euchroma].
AB  - The accumulation of rosmarinic acid, acetylshikonin, deoxyshikonin, beta, beta'
      dimethylacrylshikonin and isovalerylshikonin was investigated in cell suspension
      cultures of Arnebia euchroma (Royle) Johnst under the influence of 2-aminoindan-2
      phosphonic acid (AIP), an inhibitor of phenylalanine ammonia lyase (PAL), and of
      the effector methyl jasmonate (MeJA). The results showed that methyl jasmonate
      promoted the accumulation of rosmarinic acid and shikonin derivatives.
      Conversely, 2-aminoindan-2-phosphonic acid suppressed the formation of rosmarinic
      acid, which indicated that AIP, indeed, was able to inhibit the phenylpropanoid
      pathway in A. euchroma. Meanwhile, the content of total shinkonins and other four
      kinds of shikonin derivatives, though varied in degrees, was also inhibited. And
      the inhibition was dose-dependent and time-dependent. Acetylshikonin responsed
      most rapidly to the treatment of AIP, the content reduced after 24 h of treatment
      and decreased to only half of those untreated control 48 h after teratment. beta,
      beta'-Dimethylacrylshikonin, difffer from acetylshikonin, responded much slowly
      to the treatment, inhibition could only be observed 96 h later. These suggest
      that phenylpropanoid pathway plays an important role in the
      shikoninsbiosynthesis, and this study provides a reference for the further
      research in metabolic regulation of producing shikonins by cell culture
      technology and biosynthesis pathways of shikonin derivatives. Still, shikonins
      biosynthesis pathways is complicated, the exact dose- and time-effect
      relationship of AIP and interaction between AIP and other effectors like MeJA
      need further research.

PMID- 29071864
TI  - [Identification of Ranae Oviductus original animal based on COI sequences].
AB  - Ranae Oviductus has a high economic and social value, but its adulterants are
      more numerous, which causes a great confusion to the market. Using DNA bar code
      technology based on COI sequence for PCR amplification and sequencing of the
      identified Rana dybowskii, R. chensinensis, R. huanrensis and R. amurensiss, the
      COI gene database of four species of Rana was established, and comparing the
      measured sequence with the sequence of GenBank, four kinds of Rana were
      identified. The MEGA (molecular evolutionary genetics analysis) 7 .0 software was
      used to calculate the genetic distance of K2P and construct the NJ (neighbor
      joining) system cluster tree. The sequence of the four species of Rana measured
      were clustered into one group with the sequence of the four kinds of Rana
      downloaded from GenBank, but separated from the two outer groups downloaded from
      GenBank. The COI gene of the R. dybowskii was likely to have regional
      differences, however this technique failed to distinguish male and female Rana.
      The results showed that DNA bar code technology could accurately identify the
      base of original animal of R. oviductus. It indicates that DNA bar code COI
      provides a new method for the identification of R. oviductus.

PMID- 29071865
TI  - [Chemical constituents from tuber of Bletilla striata].
AB  - Eighteen compounds were isolated from the EtOAc soluble fraction of Bletilla
      striata by various chromatographic techniques, such as silica gel, ODS, Sephadex
      LH-20, RP-HPLC. Their structures were identified by spectroscopic methods and
      physicochemical properties, as 5-hydroxy-2-(p-hydroxybenzyl)- 3-
      methoxybibenzyl(1), shancigusins B(2), shanciguol(3),arundinan(4), 3',5-dihydroxy
      2,4-di(p-hydroxybenzyl)-3-methoxybibenzyl(5), arundin(6), 3,3'-dihydroxy-2-(p
      hydroxybenzyl)-5-methoxybibenzyl(7), 3, 3'-dihydroxy-2', 6'-bis(p-hydroxybenzyl)
      5-methoxybibenzyl(8), 7-hydroxy-2,4-dimethoxyphenanthrene(9), bleformin
      B(10),nudol(11), 3,7-dihydroxy-2, 4-dimethoxyphenanthrene(12), 2, 7-dihydroxy-4
      methoxy-9,10-dihydrophenathrene(13), bleformin D(14), 4,4'-dimethoxy-9,10-dyhydro
      [6,1'-biphenanthrene]-2,2',7,7'-tetraol(15),gymconopin C(16),(2,3-trans)-2-(4
      hydroxy-3-methoxyphenyl)-3-hydroxymethyl-10-methoxy-2,3,4,5-tetrahydro
      phenanthro[2,1-b]furan-7-ol(17),shanciol(18). Among them, compound 1 was a new
      compound, Compounds 2-6,9,15-18 were isolated from this genus for the first time.

PMID- 29071866
TI  - [Antiasthmatic effects of different tonifying kidney-Yin formulas and their
      effects on airway remodeling in chronic asthma].
AB  - Both of Zuogui Wan(ZGW) and Liuwei Dihuang Wan(LWDHW) contain ingredients of
      Sanbufang(SBF), which have been proven to have antiasthmatic effects. In order to
      study the antiasthmatic effects of the three tonifying kidney-Yin formulas and
      their mechanisms, BALB/c mice were randomly divided into 5 groups. Chronic asthma
      was induced by ovalbumin. Mice in treated groups were respectively given 49.0
      g*kg-1ZGW, 35.0 g*kg-1LWDHW and 22.4 g*kg-1SBF by gavage. Those in normal and
      model group were given normal saline. After treatment, sneeze and nose scratching
      times of mice were observed. Histological lung sections were prepared to
      determine the basement membrane thickness(BMT), smooth muscle thickness(SMT),
      collagen area(CA) and numbers of goblet cells(GCN). Western blotting and RT-PCR
      were used to determine the expression levels of MMP-9, TGF-beta1, Smad2, Smad3
      and Smad7. The results showed that sneeze and nose scratching times of ZGW group
      were significantly lower than those of SBF group. Its inhibition degree on airway
      remodeling was significantly higher than SBF group. Sneeze and nose scratching
      times of LWDHW group were significantly lower than SBF group. Its CA and GCN were
      significantly lower than SBF group. Regarding the four airway remodeling related
      factors, MMP-9, TGF-beta1, Smad2 and Smad3 of ZGW group were significantly lower
      than those of SBF group, and its Smad7 was significantly higher than SBF. Smad7
      of LWDHW group was significantly higher than SBF. There was no significant
      difference in MMP-9 between model group and SBF group. The results indicate that
      there are significant differences in the antiasthma effect of these tonifying
      kidney-Yin formulas. The regulatory effects of ZGW and LWDHW on MMP-9 and Smad7
      may be correlated with the differences in the inhibitory effect of airway
      remodeling of the three formulas.

PMID- 29071867
TI  - [Effects of three Wenyang Jianpi Tang on cell proliferation and apoptosis of
      nonalcoholic fatty liver cells].
AB  - To investigate the effects of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang on
      the cell proliferation and apoptosis of nonalcoholic fatty liver cells through
      the nonalcoholic fatty liver cell model established by inducing L02 cells with
      oleic acid. Different concentrations of oleic acid were added into L02 cells to
      induce the nonalcoholic fatty liver cell model. Oil red O staining was used to
      observe fatty droplets of fatty liver cells. Automatic biochemical analyzer was
      used to detect the levels of aspartic transaminase(AST), alanine
      aminotransferase(ALT), total cholesterol(TC), and triglyceride(TG) in the cell
      supernatants. There were five groups, namely normal group, model group, model and
      Sijunzi Tang group, model and Lizhong Tang group, and model and Fuzi Lizhong Tang
      group. The cell proliferation and apoptosis of the five groups were detected by
      MTT colorimetry test and flow cytometer. The expressions of PCNA, cleaved caspase
      3, cleaved caspase-8, cleaved caspase-9, Bax and Bcl-2 proteins of the five
      groups were detected by Western blot. The oil red O staining results showed that
      the optimum concentration of oleic acid that was used to induce nonalcoholic
      fatty liver cell models was 80 mg*L-1. The levels of AST, ALT, TC and TG in the
      nonalcoholic fatty liver cell supernatants were higher than that in normal liver
      cell supernatants(P<0.01). MTT colorimetry test and flow cytometer results showed
      that all of Sijunzi Tang, Lizhong Tang and Fuzi Lizhong Tang could effectively
      promote the cell proliferation, and inhibit the cellular apoptosis of
      nonalcoholic fatty liver cells(P<0.01). And Fuzi Lizhong Tang showed the best
      effect. Western blot results showed that Sijunzi Tang, Lizhong Tang and Fuzi
      Lizhong Tang could down-regulate the expressions of cleaved caspase-3, cleaved
      caspase-8, cleaved caspase-9 and Bax proteins, and up-regulate the expressions of
      PCNA and Bcl-2 proteins of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang
      showed the best effect. In conclusion, all of Sijunzi Tang, Lizhong Tang and Fuzi
      Lizhong Tang could effectively promote the cell proliferation, and inhibit the
      cellular apoptosis of nonalcoholic fatty liver cells. And Fuzi Lizhong Tang
      showed the best effect. The pharmacodynamic mechanism may be related to the
      expressions of key factors in pathways related with proliferation and apoptosis
      mediated by the three decoctions.

PMID- 29071868
TI  - [Transdermal permeation of effective components in Huoxue Zhitong patch].
AB  - To establish a determination method for the contents of paeonol, eugenol and
      piperine in receptor liquid and to research the transdermal permeability of
      Huoxue Zhitong patch. The contents of paeonol, eugenol and piperine in receptor
      liquid were determined by high pressure liquid chromatography(HPLC); and the
      receptor liquid was optimized by taking accumulative amount penetrated within 24
      hours, percutaneous permeation rate and skin irritation as indexes. In vitro
      Franz diffusion experiment was applied to assess the percutaneous penetration
      characteristics and regularity of Huoxue Zhitong patch. The results showed that
      the accumulative penetration amount and penetration rate by using PEG 400-ethanol
      normal saline 3?3?4 as receptor liquid were higher than those by using propylene
      glycol?ethanol?normal saline 3?3?4 and ethanol-normal saline 3?7, the and skin
      irritation of PEG 400-ethanol-normal saline 3?3?4 was smaller than propylene
      glycol:ethanol: normal saline 3?3?4. Results of percutaneous permeability
      experiments displayed that the accumulative amount penetrated of paeonol, eugenol
      and piperine within 24 hours was 2.84, 19.9, and 0.753 MUg*cm-2 respectively in
      Huoxue Zhitong patch and the penetration rate was 0.18, 1.22, and 0.02 MUg*cm-2*h
      1 respectively. Thus, the permeation of paeonol, eugenol and piperine through the
      skin was a diffusion process, which was irrelevant to their content in patch.

PMID- 29071870
TI  - [Medication rules of famous veteran traditional Chinese medicine doctor in
      treatment of chronic bronchitis based on implicit structure model].
AB  - To explore the medication rules of famous veteran traditional Chinese medicine
      (TCM) doctors in treatment of chronic bronchitis, a structured medical record
      database for famous veteran TCM doctors in modern clinical books was established.
      First, Lantern 3.1.2(Kongmin light) implicit structure analysis software was used
      to build an implicit structure model and make an implicit interpretation. Then,
      SAS 9.1 was adopted to mine herb-herb, herb-symptom and herb-syndrome association
      rules. Through the mining, 1 274 commonly used herbs for chronic bronchitis were
      found, including liquorice, bitter almond, pinellia, dried tangerine or orange
      peel, poria cocos. The medicine types included antiasthmatic medicine, qi
      tonifying medicine, and heat-phlegm removing medicine. The medicine tastes
      included sweet, pungent and bitter. The meridian distributions included lung,
      spleen and stomach channels. The famous commonly used prescriptions included
      Xiaoqinglong decoction, Maxing Shigan decoction and Erchen decoction. The 147
      herb implicit structure model for the first diagnosis was built to get 44 hidden
      variables, 88 hidden classes, 7 comprehensive clustering models, 9 dual herb
      associations, 50 triple herb associations and 89 quadruple associations. Totally
      297 medical records for the second diagnosis were compared to obtain 24 herb
      symptom associations, which reduced ephedra, bitter almond, pinellia and added
      poria cocos, atractylodes, dangshen, 20 dual herb associations and 8 triple herb
      associations. A model for the top 83 symptoms and top 96 herbs in the first
      diagnosis was built to get 50 hidden variables and 101 hidden classes. The
      commonly used herbs of famous veteran TCM doctors included bitter almond,
      pinellia, dried tangerine or orange peel, poria cocos, which feature mild
      property and sweet favor and enter lung, spleen, kidney meridians; the commonly
      herbal pairs included atractylodes and poria cocos, asarum, fructus schisandrae
      and pinellia, as well as poria cocos, dangshen, pinellia and dried tangerine or
      orange peel. The herb-syndrome associations involved ephedra, bitter almond,
      cassia twig and scanty sputum, pinellia and external cold and internal fluid
      syndrome, turbid phlegm obstructing lung syndrome and spleen deficiency syndrome,
      bitter almond and turbid phlegm obstructing lung syndrome, phlegm-heat
      accumulated in the lung and wind-cold invading the lung. The implicit structure
      model can be used to quantify tacit knowledge of TCM, extend to the herb and
      syndrome level for the first time, and quantify the major, minor and compatible
      statues of different variables in the same data. This study concluded that the
      medication rules of famous veteran TCM doctors in treatment of chronic bronchitis
      have certain reference value for the clinical diagnosis and treatment. The data
      sources, analysis methods and mining results were relatively reliable and
      objective, and can provide a reference for rules of other disease treatment based
      on syndrome differentiation.

PMID- 29071869
TI  - [Effects of wine processed Rheum palmatum on tissue distribution of aloe-emodin,
      rhein and emodin in rats].
AB  - Under the traditional processing theory "wine processing could promote the
      efficacy", Rhubarb after wine processing could treat the upper energizer diseases
      such as red swelling, and breath sores. Processing changes the medicinal
      properties of rhubarb, and thus results in different focuses in clinical
      application. In this study, a sensitive and specific method was developed for the
      determination of aloe-emodin, rhein and emodin in rats tissue. Rhubarb raw
      materials and its wine processed decoction were given to SD rats respectively by
      gavage administration, and then the contents of aloe-emodin, rhein and emodin in
      the tissues (heart, lung, brain, liver, kidney) were determined by HPLC-MS to
      explore the effect of wine processing on free anthraquinones in rat tissues.
      Experimental results showed that wine processing can significantly change the
      distribution of aloe emodin, rhein and emodin in rats in vivo, and the
      distribution of these components was increased in heart and lung tissues.There
      was no significant change of distribution in the liver and the kidney as compared
      with raw product group, and these three ingredients were not detected in the
      brain, indicating that aloe-emodin, rhein, emodin can not pass through the blood
      brain barrier.Therefore, wine processing had greater effect on distribution of
      free anthraquinones in rat tissues.This also verified the theory of traditional
      Chinese medicine, providing experimental basis for rhubarb processing mechanism.

PMID- 29071871
TI  - [Expression of SRD5A1 and its prognostic role in prostate cancer: Analysis based
      on the data-mining of ONCOMINE].
AB  - Objective: To explore the expression of I-5alpha-reductase (SRD5A1)and its
      prognostic role in prostate cancer . METHODS: Data about SRD5A1 were retrieved
      from the ONCOMINE database and the role of SRD5A1 in prostate cancer was
      analyzed. RESULTS: Totally, 992 studies of different types relevant to the
      expression of SRD5A1 were identified in the ONCOMINE database. The SRD5A1
      expression was statistically significant in 239 of the studies, overexpressed in
      157 (11 in prostate cancer) and underexpressed in the other 82 (3 in prostate
      cancer). Eighteen of the studies, with 1 068 samples, addressed the expression of
      SRD5A1 in prostate cancer and normal tissues, which was significantly higher in
      the former than in the latter tissue (P<0.05). In 3 of the studies, the SRD5A1
      expression was high in primary prostate cancer and increased with its metastasis
      (P<0.0 5). Two of the studies with prognostic data showed a higher rate of
      postoperative biochemical recurrence and a higher total mortality rate in the
      patients with a high than in those with a low expression of SRD5A1 (P<0.05).
      CONCLUSIONS: SRD5A1 is highly expressed in prostate cancer, especially in
      metastatic and castration-resistant prostate cancer and its expression is
      associated with the prognosis of prostate cancer, which may be an important
      target of medication for prostate cancer.

PMID- 29071872
TI  - [Correlation between premature ejaculation diagnostic tool and International
      Index of Erectile Function-15 in different types of premature ejaculation].
AB  - Objective: To investigate the correlation between the premature ejaculation
      diagnostic tool (PEDT) and International Index of Erectile Function-15 (IIEF-15)
      in different types of premature ejaculation (PE). METHODS: We performed a cross
      section survey among 352 PE patients received in the andrology clinic from
      December 2014 to December 2015 and 104 healthy men from the health examination
      center using basic demographic information (as on age, height, weight, education
      status, occupation, income, etc.), PEDT results, and IIEF-15 scores of the
      subjects. RESULTS: The PE patients had remarkably higher PEDT and lower IIEF-15
      scores than the healthy men (P<0.01). The PEDT score of the PE patients was
      negatively correlated with their total IIEF-15 score as well as with the scores
      in the domains of erectile function, sexual intercourse satisfaction, and overall
      satisfaction after adjusted for age (P<0.01). The patients with acquired PE (APE)
      showed a lower IIEF-15 score than those with lifelong PE (LPE) (P<0.01). The PEDT
      score of the APE patients was correlated negatively with the total IIEF-15 score
      (r=-0.391, P<0.01) and the scores in the domains of erectile function (r=-0.362,
      P<0.01) and overall satisfaction (r=-0.621, P<0.01), but not correlated with
      intercourse satisfaction, sexual orgasm, or sexual desire. The PEDT score of the
      LPE group was correlated negatively with intercourse satisfaction (r=-0.286,
      P<0.05) but not correlated with either the total IIEF-15 score or the scores in
      the domains of erectile function, overall satisfaction, sexual orgasm, or sexual
      desire. CONCLUSIONS: PE patients have a higher PEDT score and a lower IIEF-15
      score than normal males. The PEDT score of APE patients is significantly
      correlated with the total IIEF-15 score, while that of LPE patients is correlated
      not with the total IIEF-15 score but with intercourse satisfaction.

PMID- 29071873
TI  - [Focusing on MRI-suspected lesions in targeted transrectal prostate biopsy guided
      by MRI-TRUS fusion imaging for the diagnosis of prostate cancer].
AB  - Objective: To improve the accuracy of prostate cancer (PCa) detection by focusing
      biopsy on the suspected lesion manifested by MRI with the total number of biopsy
      cores relatively unchanged. METHODS: A prospective randomized analysis was
      performed on 262 cases of suspected PCa detected by multi-parametric MRI (mp
      MRI), each with a single suspected lesion with 10 MUg/L<= PSA <20 MUg/L. All the
      patients underwent targeted transrectal prostate biopsy guided by fusion imaging
      of MRI with transrectal ultrasonography (TRUS), using the 6X+6 strategy (6 cores
      in the suspected region and another 6 in the systematic prostate) for 134 cases
      and the traditional 12+2X method (12 cores in the systematic prostate and 2 in
      the suspected region) for the other 128. Comparisons were made between the two
      methods in the PCa detection rate in the cases of suspected lesion, total PCa
      detection rate, incidence of post-biopsy complications, and Gleason scores.
      Analyses were performed on the prostate imaging reporting and data system (PI
      RADS) score, location, transverse section, and diameter of the suspected lesion.
      RESULTS: Both the total PCa detection rate and that in the cases of suspected
      lesion were significantly higher in the 6X+6 (44.8% and 37.3%) than in the 12+2X
      group (37.5% and 27.3%) (P<0.05). MRI showed that the suspected lesions were
      mostly (45%) located in the middle part of the prostate, the mean area of the
      transverse section was (0.48+/-0.11) cm2, and the mean diameter of the tumor was
      (8.51+/-2.21) mm. The results of biopsy showed that low-grade tumors (Gleason
      3+3=6) accounted for 68% in the 6X+6 group and 71% in the 12+2X group. No
      statistically significant differences were found between the two groups in the
      incidence rate of post-biopsy complications. CONCLUSIONS: Compared with the
      traditional 12+2X method, for the suspected lesion manifested by mp-MRI, focusing
      biopsy on the suspected region with the 6X+6 strategy can achieve a higher PCa
      detection rate without increasing the incidence of complications.

PMID- 29071874
TI  - [Diagnostic value of high-field MRI for Peyronie's disease].
AB  - Objective: To analyze the MRI manifestations of Peyronie's disease and
      investigate the value of high-field MRI in the diagnosis of the disease. METHODS:
      Using a small surface coil, we performed 3.0 Tesla MRI for 14 patients with
      clinically diagnosed Peyronie's disease. The MRI protocol included routine
      sequences (T1WI, T2WI, and enhanced T1WI) and susceptibility-weighted imaging
      (SWI). Each patient had received 2-4 penile ultrasound examinations previously.
      We compared the MRI findings with the results of ultrasonography. RESULTS: MRI
      manifested 25 penile plaques in the 14 patients, 3 (7 plaques) with inflammation,
      4 (8 plaques) with fibrosis, and the other 7 (10 plaques) with calcification
      displaying a low signal intensity on SWI. Ultrasonography had revealed the 10
      calcified plaques in all the 20 examinations, but exhibited the 7 inflammatory
      and 8 fibrotic ones in only 3 of the 23 examinations. The combination of MRI SWI
      sequences was necessitated for the detection of calcified plaques and achieved
      higher detection rates than ultrasonography for inflammatory and fibrotic plaques
      (P<0.05). CONCLUSIONS: High-field MRI has high sensitivity and accuracy in the
      diagnosis of Peyronie's disease, which can effectively display penile plaques of
      different nature in the early stage through multi-parametric sequences.

PMID- 29071875
TI  - [Oral-appliance combined with tadalafil for erectile dysfunction induced by
      severe obstructive sleep apneahypopnea syndrome].
AB  - Objective: To evaluate the effect of the oral-appliance combined with tadalafil
      in the treatment of erectile dysfunction (ED) induced by severe obstructive sleep
      apnea-hypopnea syndrome (OSAHS). METHODS: We equally randomized 90 patients with
      severe OSAHS-induced ED to groups A, B, and C to be treated with the oral
      appliance, tadalafil (10 mg daily qd), and oral-appliance plus tadalafil,
      respectively, all for 3 months. Then we compared the therapeutic effects among
      the three groups of patients using the IIEF-5 questionnaire, Sexual Encounter
      Profile (SEP) diaries, and the intercourse satisfaction rate of the patients'
      partners. RESULTS: Totally 87 of the patients accomplished the treatment, 29 in
      group A, 30 in B, and 28 in C. After treatment, group C, as compared with A and
      B, showed significant increases in the IIEF-5 score (4.18+/-1.19 vs 2.66+/-1.63
      and 2.77+/-1.74, P=0.009 and P=0.026), the success rate of penile intromission
      (SEP2) (85.7% vs 58.6% and 53.3%, P=0.023 and P=0.008), and the success rate of
      intercourse (SEP3) (64.3%% vs 37.9% and 33.3%, P=0.047 and P=0.018). The overall
      satisfaction of the female partners was remarkably higher in groups A and C than
      in B (P=0.027 and P=0.007). CONCLUSIONS: Oral-appliance combined with tadalafil
      can improve erectile function in patients with severe OSAHS-induced ED, with a
      better efficacy than either of them used alone.

PMID- 29071876
TI  - [Familial fragile X syndrome: A pedigree analysis].
AB  - Objective: To investigate the clinical (including reproductive) manifestations
      and genetic characteristics of familial fragile X syndrome (FXS). METHODS: We
      collected the clinical data about a case of familial FXS by inquiry, testicular
      ultrasonography, semen analysis, determination of sex hormone levels, and
      examinations of the peripheral blood karyotype and Y chromosome microdeletions.
      Using Southern blot hybridization, we measured the size of the CGG triple repeat
      sequence of the fragile X mental retardation-1 (FMR1) gene and determined its
      mutation type of the pedigree members with a genetic map of the FXS pedigree.
      RESULTS: Among the 34 members of 4 generations in the pedigree, 3 males and 1
      female (11.76%) carried full mutation and 9 females (26.47%) premutation of the
      FMR1 gene. Two of the males with full FMR1 mutation, including the proband showed
      a larger testis volume (>30 ml) and a higher sperm concentration (>250 *106/ml),
      with a mean sperm motility of 50.5%, a mean morphologically normal sperm rate of
      17.5%, an average sperm nuclear DNA fragmentation index (DFI) of 18.5%, a low
      level of testosterone, normal karyotype in the peripheral blood, and integrity of
      the azoospermia factor (AZF) region in the Y chromosome. One of the second
      generation females carrying FMR1 premutation was diagnosed with premature ovarian
      failure and another 3 with uterine myoma. CONCLUSIONS: Some of the FXS males in
      the pedigree may present macroorchidism and polyzoospermia but with normal semen
      parameters. In the intergenerational transmission, premutation might extend to
      full mutation, with even higher risks of transmission and extension of mutation
      in males, especially in those with >80 CGG triple repeat sequences. Therefore, it
      is recommended that the couples wishing for childbearing receive genetic testing,
      clinical guidance, and genetic counseling before pregnancy and, if necessary,
      prenatal diagnosis and preimplantation genetic diagnosis.

PMID- 29071877
TI  - [Impact of unilateral cryptorchidism on the levels of serum anti-mullerian
      hormone and inhibin B].
AB  - Objective: To investigate the influence of unilateral cryptorchidism on the
      levels of serum anti-mullerian hormone (AMH) and inhibin B in children. METHODS:
      We enrolled 65 patients with unilateral cryptorchidism and 45 healthy children in
      this study. We measured the length and circumference of the penis, the testis
      volume in the cryptorchidism side, and the levels of serum AMH and inhibin B at
      the age of 6 and 12 months, respectively. RESULTS: Compared with the healthy
      controls, the patients with unilateral cryptorchidism showed significant
      decreases at 12 months in serum AMH ([108.06+/-12.40] vs [103.26+/-17.57] ng/ml,
      P<0.05) and inhibin B ([77.43+/-5.66] vs [70.21+/-5.69] pg/ml, P<0.05). No
      statistically significant differences were found in the length and circumference
      of the penis and the testis volume in the cryptorchidism side at 6 and 12 months
      (P>0.05), or in the levels of serum AMH and inhibin B at 6 months (P>0.05).
      CONCLUSIONS: Unilateral cryptorchidism affects the gonadal function of the
      patient, and orchiopexy should be timely performed in order to reduce its impact.

PMID- 29071878
TI  - [Transumbilical single-port laparoscopy combined with improved double hernia
      needles for pediatric hydrocele].
AB  - Objective: To compare the clinical effect of transumbilical single-port
      laparoscopy combined with improved double hernia needles with that of traditional
      open surgery in the treatment of hydrocele in children. METHODS: We
      retrospectively analyzed 35 cases (54 sides) of pediatric hydrocele treated by
      transumbilical single-port laparoscopy combined with improved double hernia
      needles (laparoscopy group). We recorded the operation time, intraoperative blood
      loss, hospital stay, scrotal edema, and postoperative complications and compared
      them with those of another 46 cases (58 sides) treated by traditional open
      surgery (open surgery group) during the same period. RESULTS: The laparoscopy
      group showed a significantly shorter operation time, less intraoperative blood
      loss, milder scrotal edema, and fewer hospital days than the open surgery group
      (all P<0.05). However, no statistically significant difference was found in the
      incidence of postoperative complications between the two groups (P>0.05).
      Subcutaneous emphysema developed in 2 patients in the laparoscopy group, which
      disappeared after 1-3 days of oxygen inhalation and other symptomatic treatment,
      while scrotal hematoma occurred in 1 and incision fat liquefaction in 2 patients
      in the open surgery group 3 days postoperatively, which healed after debridement
      suture and daily dressing, respectively. The patients were followed up for 3-6
      months, which revealed no late complications in the laparoscopy group but 1 case
      of unilateral recurrence and 2 cases of offside recurrence in the open surgery
      group, all cured by laparoscopic internal ring ligation. CONCLUSIONS:
      Transumbilical single-port laparoscopy combined with improved double hernia
      needles is superior to traditional open surgery for the treatment of pediatric
      hydrocele and therefore deserves clinical generalization.

PMID- 29071879
TI  - [Resected prostate tissue volume and postoperative short-term outcomes of
      transurethral resection of the prostate].
AB  - Objective: To evaluate the influence of the resected prostate tissue volume (RPV)
      on the improvement of International Prostate Symptom Score (IPSS), quality of
      life (QOL), and voiding function after transurethral resection of the prostate
      (TURP). METHODS: This study included 82 men with benign prostatic hyperplasia
      treated by TURP. Before and three months after TURP, we obtained the IPSS, QOL
      score, post-voiding residual urine volume (PVR), and maximum urinary flow rate
      (Qmax) from the patients. We measured the total prostate volume (TPV) and
      transition zone volume (TZV) by transrectal ultrasound preoperatively and
      investigate the influence of the RPV, RPV/TZV ratio, and RPV/TPV ratio on the
      efficiency of TURP. RESULTS: At three months after TURP, the mean Qmax increased
      by 9.27 ml/s, IPSS decreased by 15.86, QOL score increased by 3.47, PVR decreased
      by 87.1 ml, and 72.0% of the patients felt satisfied with the surgical results.
      There was no statistically significant difference in RPV between the patients
      satisfied and those dissatisfied with the results. Both the RPV/TPV and RPV/TZV
      ratios significantly increased in the satisfaction group as compared with the
      dissatisfaction group (P=0.002 and P=0.004). The areas under the ROC curve for
      the RPV/TPV and RPV/TZV ratios were 0.793 (P=0.001) and 0.687 (P=0.009),
      respectively. CONCLUSIONS: RPV is closely related to the short-term outcomes of
      TURP, and the ratios of RPV/TPV and RPV/TZV may be used as new markers to predict
      the outcomes of TURP.

PMID- 29071880
TI  - [Efficacy and safety of Yimusake Tablets plus dapoxetine hydrochloride in the
      treatment of premature ejaculation].
AB  - Objective: To evaluate the effect and safety of Yimusake Tablets combined with
      dapoxetine hydrochloride and either of them used alone in the treatment of
      premature ejaculation (PE). METHODS: We randomly assigned 180 PE patients to oral
      medication of Yimusake Tablets at 1.5 g per night (group A), dapoxetine
      hydrochloride at 30 mg at 1-3 hours before anticipated sexual activity (group B),
      the Yimusake Tablets plus dapoxetine hydrochloride simultaneously (group C), all
      for 8 weeks. After 4 and 8 weeks of medication, we recorded and compared the
      changes in the intravaginal ejaculation latency time (IELT), measures of the PE
      profile (PEP), and adverse events among the three groups of patients. RESULTS:
      The treatment was accomplished and complete data obtained from 154 of the
      patients, 56 in group A, 52 in group B, and 46 in group C. After 4 and 8 weeks of
      medication, the mean IELT was dramatically prolonged in all the three groups as
      compared with the baseline (P<0.01), most significantly at 8 weeks in group C
      ([2.08+/-0.68] min), followed by B ([1.76+/-0.52] min) and A ([1.47+/-0.44] min),
      with statistically significant differences among the three groups (P<0.01). The
      PEP measures were remarkably improved in group A at 8 weeks (P<0.05), and both in
      B and C at 4 and 8 weeks (P<0.05), most significantly at 8 weeks in group C
      (P<0.05), in which the patients scored 1.96+/-0.77 in perception of control over
      ejaculation, 2.62+/-0.98 in satisfaction with sexual intercourse, 3.04+/-0.62 in
      PE-related distress, and 3.57+/-0.80 in PE-induced difficult relationship with
      their partners, all markedly improved as compared with groups A and B (P<0.05).
      Adverse reactions were observed in 2 cases (3.6%) in group A, 6 cases (9.6%) in
      B, and 5 cases (10.9%) in C. No severe adverse events occurred in any of the
      patients during the study. CONCLUSIONS: Combined medication of Yimusake Tablets
      and dapoxetine hydrochloride, with its advantages of effectiveness and safety,
      deserves to be recommended for the treatment of PE.

PMID- 29071881
TI  - [Qilin Pills for obstructive azoospermia after ejaculatory duct reconstruction].
AB  - Objective: To observe the clinical effect of Qilin Pills in the treatment of
      severe oligozoospermia after microsurgical ejaculatory duct reconstruction for
      obstructive azoospermia. METHODS: We retrospectively analyzed 75 cases of
      obstructive azoospermia treated by ejaculatory duct reconstruction followed by
      administration of Qilin Pills. The patients were divided into a Qilin group
      (n=42) and a control group (n=33) postoperatively, treated with Qilin Pills and
      placebo, respectively. After 3 months of medication, we compared the sperm
      quality between the two groups of patients. RESULTS: After 3 months' treatment,
      all the patients experienced remarkable improvement in sperm quality (P<0.05).
      Compared with the controls, the patients in the Qilin group showed dramatic
      increases in sperm concentration, from (0.57+/-0.25) and (0.60+/-0.18) *106/ml
      before medication to (2.83+/-0.59) and (1.72 +/-0.52) *106/ml after medication,
      significantly higher in the Qilin than in the control group (P<0.05). The
      percentage of grade a sperm was increased from (5.52+/-5.97) and (5.30+/-6.26)%
      to (11.56+/-9.96) and (10.27+/-6.52)%, that of grade a+b sperm from (9.68+/-8.63)
      and (8.64+/-10.10)% to (23.42 +/-14.10) and (20.81+/-14.70)%, and that of
      morphologically normal sperm from (2.00+/-1.27) and (2.31+/-0.94)% to (3.54+/
      2.47) and (3.47+/-1.33)%, respectively. No statistically significant differences
      were observed in sperm motility and normal sperm morphology between the two
      groups after treatment (P>0.05). The total effectiveness rate was higher in the
      Qilin group than in the controls (88.1% vs 72.7%), but with no significant
      difference between the two groups (P>0.05). CONCLUSIONS: Qilin Pills are fairly
      effective in improving the quantity of sperm in obstructive azoospermia patients
      after ejaculatory duct reconstruction.

PMID- 29071882
TI  - [Protective effect of Wuziyanzong Pills on rats with experimental
      oligoasthenospermia and its action mechanism].
AB  - Objective: To investigate the protective effect of Wuziyanzong Pills (WYP) in the
      rat model of oligoasthenospermia (OAS) and its action mechanism. METHODS: Sixty
      male SD rats were equally randomized into six groups: normal control, OAS model,
      Shengjing Capsules (1.6 g per kg of the body weight), low-dose WYP (1 g per kg of
      the body weight), medium-dose WYP (2 g per kg of the body weight), and high-dose
      WYP (4 g per kg of the body weight). The OAS model was established by
      intragastric administration of Tripterygium glucoside at 30 mg per g per d for 6
      weeks. From the 3rd week of modeling, the rats of the medication groups were
      treated intragastrically with corresponding drugs for 4 weeks. Then all the rats
      were sacrificed for measurement of the testicular and epididymal organ
      coefficients, examination of epididymal sperm quality and apoptosis, and
      detection of the openness of the sperm mitochondrial permeability transition pore
      (MPTP). Histopathological changes in the testis were observed by HE staining and
      the apoptosis of spermatogenic cells determined by Hochest staining. RESULTS: WYP
      obviously improved the organ coefficients of the testis and epididymis, increased
      sperm concentration, motility and viability, decreased the apoptosis of
      spermatogenic cells, and inhibited the abnormal openness of MPTP in the OAS model
      rats. HE staining showed that the number and levels of spermatogenic cells were
      significantly increased while Hochest staining manifested that the apoptosis of
      spermatogenic cells was remarkably inhibited in the seminiferous tubules of the
      testis in the WYP-treated rats. CONCLUSIONS: WYP can improve sperm quality and
      reduce the apoptosis of spermatogenic cells (including sperm) in OAS model rats,
      which may be related with its inhibitory effect on the abnormal openness of MPTP.

PMID- 29071883
TI  - [Ubiquitin-proteasome system and sperm DNA repair: An update].
AB  - The ubiquitin-proteasome system (UPS) is a proteasome system widely present in
      the human body, which is composed of ubiquitin (Ub), ubiquitin activating enzymes
      (E1), ubiquitin conjugating enzymes (E2), ubiquitin protein ligases (E3), 26S
      proteasome, and deubiquitinating enzymes (DUBs) and involved in cell cycle
      regulation, immune response, signal transduction, DNA repair as well as protein
      degradation. Sperm DNA is vulnerable to interference or damage in the progression
      of chromosome association and homologous recombination. Recent studies show that
      UPS participates in DNA repair in spermatogenesis by modulating DNA repair
      enzymes via ubiquitination, assisting in the identification of DNA damage sites,
      raising damage repair-related proteins, initiating the DNA repair pathway,
      maintaining chromosome stability, and ensuring the normal process of
      spermatogenesis.

PMID- 29071884
TI  - [Relaxation mechanism of smooth muscle cells and its relationship with penile
      erection].
AB  - The contractile and diastolic function of smooth muscle cells (SMCs) is closely
      related to penile erection and erectile dysfunction (ED). In addition to nitric
      oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), sulfur dioxide
      (SO2), estrogen receptor (ER), P2Y receptor, perivascular tissue (PVT), and
      calcium activated potassium channel (Kca) are found to be involved in the
      relaxation of SMCs. This review updates the mechanisms of the relaxation of SMCs
      and its relationship with ED.

PMID- 29071885
TI  - [Advances in the diagnosis and hormone replacement treatment of 46, XY disorders
      of sex development].
AB  - Disorders of sex development (DSD) is defined as a congenital condition or
      atypical development of the chromosomal, gonadal, or anatomic sex. The diagnosis,
      gender assignment, and treatment of DSD require the guidance from experienced
      multidisciplinary teams. So far there has been no consensus about it in China.
      Due to dysgenetic gonads, defects in sex steroid biosynthesis or action, or
      gonadectomy during the prepubertal years, those with DSD suffer from
      hypogonadism. The hormone replacement therapy of DSD aims at general
      physiological health and long-term prognosis as well as the avoidance of
      unnecessary genital and gonadal surgery. This review focuses on the advances in
      the studies of the diagnosis and hormone replacement therapy of 46,XY DSD.

PMID- 29071886
TI  - [Application of sentinel lymph node tracer techniques in prostate caner].
AB  - The sentinel lymph node (SLN) is the first node receiving lymphatic drainage of a
      tumor and best reflects tumor metastasis. Whether there is a micrometastasis in
      SLN determines the choice of pelvic lymph node dissection for prostate cancer and
      is closely related to later treatment and prognosis. Therefore, precise
      localization of SLN is essential. This review discusses the application of SLN
      tracer techniques, such as preoperative imaging and intraoperative
      lymphoscintigraphy and localization of SLN, in prostate cancer.

PMID- 29071888
TI  - [Effect of Acupuncture on Neurological Function and Related Differentially
      depressed Profiles in the Brain of Middle Cerebral Artery Occlusion Rats Using
      Antibody Chips Technique].
AB  - OBJECTIVE: To observe the effect of acupuncture on changes of neurological
      function and expression of proteins in the ischemic brain region in middle
      cerebral artery occlusion (MCAO) rats with protein chip technique, so as to
      reveal the profiles of cerebral proteins related to its effectiveness in
      improving cerebral ischemia (CI). METHODS: SD rats were rando-mized into sham
      operation (sham), CI model, non-acupoint and acupoint groups (n=10 in each
      group). The CI model was established by MCAO according to modified Longa's
      method. For rats of the acupoint group, "Dazhui" (CV 14), "Baihui" (GV 20) and
      "Shuigou" (GV 26) were punctured by twirling the filiform needles for about 1
      min, and repeated once again during 30 min of need-le retention, which was
      conducted once every 12 h, and 6 times altogether. The non-acupoints were about 3
      mm away from the above-mentioned acupoints and stimulated with the same method
      and same procedures. The neurological deficit score was scaled according to
      Longa's method. The differentially-expressed proteins (>= 1.5 folds in up- and
      down-regulation) in the ischemic region of the brain were detected by using
      Springbio 720 antibody chip technology. RESULTS: Compared with the sham group,
      the neurological deficit score was significantly higher in the model group
      (P<0.01), while compared with the model group, the neurological deficit scores
      were considerably in both acupoint and non-acupoint groups (P<0.05, P<0.01). The
      therapeutic effect of acupoint group was evidently superior to that of the non
      acupoint group in improving neurological function (P<0.05). Compared with the
      sham group, the differentially-expressed proteins in the ischemic brain including
      33 up-regulated and 12 down-regulated were found in the model group, mainly
      functioning in cell apoptosis, cell cycle regulation, cell differentiation and
      proliferation, cell cytoskeleton and connection, cell signal transduction, DNA
      repair and transcription factors. Compared with the model group, the
      differentially-expressed proteins including 12 up-regulated and 31 down-regulated
      in the acupoint group, and 15 up-regu-lated and 17 down-regulated in the non
      acupoint group were detected, functioning being the same as those mentioned above
      in the model group. CONCLUSIONS: Manual acupuncture stimulation of GV 14, GV 20
      and GV 26 can improve neurological function in CI rats, which may be associated
      with its function in regulating the expression of many proteins in the ischemic
      region of the brain.

PMID- 29071887
TI  - [RNA-binding protein PTB in spermatogenesis: Progress in studies].
AB  - RNA binding proteins (RBPs) regulate the function of cells by interacting with
      nascent transcripts and therefore are receiving increasing attention from
      researchers for their roles in tissue development and homeostasis. The
      polypyrimidine tract binding (PTB) protein family of RBPs are important
      posttranscriptional regulators of gene expression. Further investigations on the
      post-transcriptional regulation mechanisms and isoforms of PTB proteins in the
      spermatogenesis show that PTB protein 1 (Ptbp1) is a predominant isoform in
      mitotic cells (spermatogonia), while Ptbp2 predominates in meiotic spermatocytes
      and postmeiotic spermatids and binds to the specific 3' untranslated region (3'
      UTR) of the phosphoglycerate kinase 2 (Pgk-2) mRNA, which helps to stabilize Pgk
      2 mRNA in male mouse germ cells. In case of Ptbp2 inactivation in the testis, the
      differentiation of germ cells arrests in the stage of round spermatids, with
      proliferation of multinucleated cells in the seminiferous tubule, increased
      apoptosis of spermatocytes, atrophy of seminiferous tubules, and lack of
      elongating spermatids, which consequently affects male fertility. This article
      presents an overview on the structure of the PTB protein and its role in
      regulating mammalian spermatogenesis.

PMID- 29071889
TI  - [Characteristics of Distribution of Blood Vessels and Nerve Fibers in the Skin
      Tissues of Acupoint "Taichong" (LR 3) in the Rat].
AB  - OBJECTIVE: To investigate the microstructure (blood vessels and nerve fibers) of
      the skin tissue in "Taichong" (LR 3) region for reveling morphological
      characteristics of acupoint. METHODS: Five SD rats were used in the present
      study. The skin tissue in the region of acupoint LR 3 was taken from the dorsum
      of hind foot following transcardial perfusion with 4% paraformaldehyde. Then, the
      skin samples were sagittally or horizontally cut into sections (20 MUm or 40 MUm
      in the thickness) to be stained with Phalloidin and calcitonin gene related
      peptide (CGRP) by using fluorescent histochemistry and immunohistochemistry. The
      labeled vascular structure and nerve fibers were observed and recorded using
      fluorescent microscope and laser scanning confocal microscope. RESULTS: In the
      skin tissue of LR 3, different types of blood vessels labeled by phalliodin,
      including capillaries and glomera mainly distributing in the superficial layer of
      the dermis, and thicker blood vessels and their sub-branches mainly existing in
      the deeper layer of the dermis and the subcutaneous layer, were found. In
      addition, CGRP positive nerve fibers were found to run parallel to the thin blood
      vessels or to gather around the thicker blood vessels. From the subcutaneous la
      yer to the epidermis, blood vessels and nerve fibers coexisted and formed a
      stereo-network structure. CONCLUSIONS: In the skin of LR 3 area, there exists a
      stereo-network structure consisting of different types of blood vessels and nerve
      fibers. Although this structure is not specifically associated with acupoint area
      alone, this result may provide a new sight to further understand the
      microstructure of acupoint.

PMID- 29071890
TI  - [Effect of Electroacupuncture Intervention at Different Time-points on Locomotor
      Function and Apoptosis in Rats with Acute Spinal Cord Injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention at
      different treatment time-points on locomotor function and neuronal apoptosis in
      rats with acute spinal cord injury (ASCI), so as to explore its mechanism under
      lying improvement of ASCI. METHODS: Seventy-two female Wistar rats were randomly
      divided into sham operation, ASCI model and EA groups which were further divided
      into 4 time-points:1, 3, 7 and 14 d (n=6 at each). The ASCI model was established
      by weight-drop striking the exposed spinal cord (T10) using a NYU impactor
      device. EA (0.4-0.6 mA, 100 Hz) was applied to bilateral "Jiaji" (EX-B 2) for 30
      min, once a day for 1, 3, 7 and 14 days, respectively in the EA group. The Basso
      Beattie-Bresnahan (BBB) grading score was used to assess the animals' locomotor
      function, and H.E. staining was used to display the pathological changes of
      spinal cord injury at different time points. The TUNEL staining was used to
      detect the nerve cell apoptosis of spinal cord tissue. RESULTS: After ASCI, the
      BBB scores were significantly decreased and the numbers of the apoptotic nerve
      cells considerably increased on day 1, 3, 7 and 14 in the model group compared
      with the sham operation group (P<0.05). In addition, H.E. staining showed severe
      damage of the spinal cord tissue, infiltration of inflammatory cells, increase of
      dead nerve neurons and glia cells in the number from day 3 to 7, and additional
      increase of vacuoles on day 14. Following EA intervention, the decrease of BBB
      scores and the increase of apoptotic nerve cell numbers were markedly suppressed
      on day 3, 7 and 14 (P<0.05). The TUNEL staining showed a decrease of the
      apoptotic nerve cells from day 3 on and an improvement of the injured tissue
      structure from day 7 to 14 in the EA group. CONCLUSIONS: EA stimulation of EX-B 2
      can significantly improve locomotor function, and lighten the spinal cord injury
      in ASCI rats, presenting a time-dependant tendency, which may be associated with
      its effect in reducing neuronal apoptosis in the spinal cord.

PMID- 29071891
TI  - [Effect of Electroacupuncture at "Zusanli"(ST 36) on the Expression of
      Ghrelin/cAMP/PKA in the Jejunum in Rats with Spleen Qi Deficiency Syndrome].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST 36)
      on Ghrelin/cAMP/PKA expression in the jejunum in rats with spleen qi deficiency
      syndrome, so as to reveal its underlying mechanism in improving energy
      metabolism. METHODS: Forty male SD rats were randomly divided into 4
      groups:normal group, spleen qi deficiency syndrome (model) group, EA group and
      non-acupoint group (n=10 in each group).The model of spleen qi deficiency
      syndrome was established by improper diet and overstrain. EA (2 Hz/15 Hz, 0.5 mA)
      was applied to bilateral "Zusanli" (ST 36) in the EA group and non-acupoint in
      non-acupoint group for 20 min, once a day for 6 days. The pathologic changes of
      the jejunum tissue were detected by H&E staining. Ghrelin, ATP and cAMP levels in
      jejunum tissue were determined by ELISA. The expression levels of PKA protein in
      jejunum tissue were determined by Western blot. RESULTS: H&E staining showed that
      the intestinal villi of the model group were swelling, shortening and thickening,
      with a damaged or broken top-part in the model group, and basically restored to
      normal after EA treatment. ELISA results showed that the contents of Ghrelin, ATP
      and cAMP in the jejunum tissue were significantly lower in the model group than
      in the normal group (P<0.05), while significantly higher in the EA group than in
      the model group (P<0.05). Western blot results showed that the expression of PKA
      protein in the jejunum tissue was significantly lower in the model group than in
      the normal group (P<0.05), and significantly higher in the EA group than in the
      model group and non-acupoint group (P<0.05). CONCLUSIONS: EA at ST 36 can improve
      the morphological changes in the jejunum of spleen qi deficiency rats, which may
      be associated with its effects in increasing Ghrelin, ATP and cAMP contents, and
      up-regulating PKA expression, leading to an increase of energy metabolism and
      spleen qi at last.

PMID- 29071892
TI  - [Grain-Moxibustion may Protect Myocardium by Reducing Oxidative Stress in
      Doxorubicin-induced Cardiomyopathy Rats].
AB  - OBJECTIVE: To observe the effectiveness of grain-moxibustion in resisting
      oxidative stress in doxorubicin (DOX)-induced cardiomyopathy rats. METHODS: Sixty
      Sprague-Dawley (SD) rats were randomly divided into blank control group (blank
      group), cardiomyopathy model (model) group and grain-moxibustion (moxibustion)
      group, with 20 rats in each one. The cardiomyopathy model was established by
      intraperitoneal injection of DOX (0.5 mg/100 g), once a week for 4 weeks. Grain
      moxibustion was applied to "Guanyuan" (CV 4) and "Juque" (CV 14) for 5 cones,
      once daily for 4 weeks except the Sundays. The rats' heart rate (HR), left
      ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP),
      left ventricular pressure maximum rising rate (+dp/dtmax), left ventricular
      pressure maximum decline rate (-dp/dtmax), left ventricular pressure change time
      (t-dp/dtmax) were detected to evaluate the cardiac function by using a
      physiological signal acquisition-analysis system. The pathological changes of the
      myocardium were observed by optical microscopy after H.E. staining. The activity
      of serum lactate dehydrogenase(LDH), creatine kinase(CK) and myocardial
      superoxide dismutase (SOD), and myocardial malondialdehyde (MDA) and serum
      cardiac troponin I(cTnI) contents were assayed by enzyme-linked immuno sorbent
      assay kit (ELISA). RESULTS: Following modeling, the HR, LVSP, +dp/dtmax, 
      dp/dtmax, and myocardial SOD activity were significantly down-regulated (P<0.05,
      P<0.01), while the LVDP, t-dp/dtmax, serum LDH and CK activity and cTnI content,
      as well as myocardial MDA content were considerably increased in comparison with
      the blank group (P<0.05, P<0.01). After moxibustion intervention, the decreased
      HR, LVSP, +dp/dtmax, -dp/dtmax, and myocardial SOD activity levels and the
      increased LVDP, t-dp/dtmax, serum LDH and CK activity and cTnI content, as well
      as myocardial MDA content were remarkably suppressed in comparison with the model
      group (P<0.05, P<0.01). CONCLUSIONS: Grain-moxibustion can significantly improve
      the left ventricular function, increase heart rate in cardiomyopathy rats, which
      may be associated with its effects in reducing myocardial oxidative stress damage
      by down-regulating the content of MDA and up-regulating SOD activity in the
      heart.

PMID- 29071893
TI  - [Influence of Electroacupuncture Intervention on Glutamic Acid and Ca2+ Contents
      and Expression of NMDA Receptor Protein in Hippocampus in Vascular Dementia
      Rats].
AB  - OBJECTIVE: To observe the influence of electroacupuncture (EA) intervention on
      hippocampal glutamate (Glu) and Ca2+ contents, and expression of Glu-N-methyl-D
      aspartic acid receptor(NMDAR) and the learning-memory ability in vascular
      dementia (VD) rats, so as to reveal its mechanisms underlying improvement of VD.
      METHODS: SD rats were rando-mized into sham operation (sham) group (n=9), model
      group (n=11) and EA groups (n=10). The VD model was established by repeated
      bilateral common carotid arteries occlusion and reperfusion plus intraperitoneal
      injection of sodium nitroprusside. EA (2 Hz, 2 mA) was applied to "Baihui" (GV
      20)-"Housanli" (ST 36) and "Geshu" (BL 17)-"Dazhui" (GV 14) for 10 min, once a
      day for 15 consecutive days. The neurological function was assessed by using
      stroke index (0-10 points) and neurological deficit scaling(0-10 points). The
      learning-memory ability was evaluated by using step-down tests. The contents of
      Glu and Ca2+ in the right hippocampal tissue were determined by using
      aspectrophotometer and the expression of NMDAR protein in the right hippocampus
      was detected by immunoblotting. RESULTS: Compared with the sham group, the stroke
      index and neurological deficit scores, and the reaction latency and the error
      times of step-down tests, as well as the contents of Glu and Ca2+ and the
      expression level of NMDAR in the right hippocampus were significantly increased
      in the model group (P<0.05, P<0.01), while the step-through latency was
      considerably decreased (P<0.01), suggesting a neurological disorder and a
      cognitive decline. After EA intervention, the reaction latency and error times of
      step-down tests, the contents of Glu and Ca2+ and the expression level of NMDAR
      in the right hippocampus were significantly down-regulated, and the step-through
      latency was notably increased in comparison with the model group (P<0.01).
      CONCLUSIONS: EA intervention is able to improve the cognitive ability of VD rats,
      which may be associated with its effects in reducing the excitatory neurotoxicity
      of hippocampal Glu-NMDAR and lowering cellular Ca2+ load to resist neuronal
      injury.

PMID- 29071894
TI  - [Effect of Electroacupuncture Stimulation of Heart Meridian on Autonomic Nervous
      Activities in Acute Myocardial Ischemia Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of the
      Heart Meridian on electrical activities of neck sympathetic and vagal nerves in
      acute myocardial ischemia (AMI) rats. METHODS: Thirty SD rats were randomly
      divided into 3 groups, sham operation (sham), model and EA(n=10 rats in each
      group). The left anterior descending branch (LADB) of the coronary artery was
      occluded to make an acute myocardial ischemia (AMI) model.For rats of the sham
      group, a surgical suture was simply threaded beneath the LADB without ligation.
      EA stimulation (2 Hz, 1 mA)was applied to bilateral "Shenmen" (HT 7), "Tongli"
      (HT 5) and the middle-point between HT 7 and HT 5 for 20 min. The electrical
      activities of the left cervical sympathetic and vagal nerves were recorded using
      a bipolar platinum wire electrodes and a BIOPAC MPl 50 system, and the
      electrocardiogram (ECG) of the standard limb lead II was recorded simultaneously.
      The AMI severity was evaluated by using J-spot height of ECG. RESULTS: After AMI,
      the heart rate (HR), J-spot of ECG, and the discharge frequency of the cervical
      sympathetic nerve were significantly increased in the model group compared with
      the sham group (P<0.01), while the discharge frequency of vagal nerve was
      obviously decreased (P<0.01). Following EA stimulation, the increased levels of
      HR, J-spot height and discharge frequency of sympathetic nerve, and the decreased
      discharge frequency of vagus were significantly suppressed at time-points of 1,
      3, 5 and 15 min after EA (P<0.01). In addition, the ratio of discharge
      frequencies of vagal/sympathetic nerves was notably down-regulated after AMI
      (P<0.01). After EA stimulation, the ratios of vagal/sympathetic discharge at the
      time-points of 1, 3, 5 and 15 min following EA were significantly increased
      (P<0.01). CONCLUSIONS: EA stimulation of the Heart Meridian may improve AMI by
      inhibiting sympathetic discharges and elevating vagal discharges in AMI rats,
      i.e., coordinating activities of the autonomic nerve systems.

PMID- 29071895
TI  - [Effect of Mild Moxibustion with Different Terms at Different Acupoints on Renal
      Functions and Renal Pathological Changes in Focal Segmental Glomerulosclerosis
      Rats].
AB  - OBJECTIVE: To observe changes of urinary microprotein, and serum creatinine, urea
      nitrogen and uric acid levels in focal segmental glomerulosclerosis (FSGS) rats
      treated by mild moxibustion, so as to explore the mechanism of moxibustion
      underlying improvement of FSGS. METHODS: SD rats were randomized into normal
      control (normal), sham operation (sham), model, medication (Losartan),
      moxibustion-Shenshu (BL 23) and moxibustion-Geshu (BL 17) groups. The latter two
      moxibustion groups were further divided into 10 min, 20 min and 30 min subgroups
      (n=6 in each group/subgroups). The FSGS model was established by unilateral
      nephrectomy combined with injection of Losartan into the tail vein twice. Mild
      moxibustion was applied to bilateral BL 17 and BL 23 for 10, 20 and 30 min,
      respectively, once every other day, for 12 weeks. The contents of urinary
      microglobulin alpha 1, micro-albumin, transferring and IgG were assayed using
      enzyme linked immunosorbent assay (ELISA), and serum creatinine, urea nitrogen
      and uric acid contents (indexes of renal function) determined using an automatic
      biochemical analyzer. The pathological changes of the kidney tissue was observed
      by using a microscope after periodic acid schiff (PAS) staining. RESULTS: No
      significant differences were found between the normal control and sham groups in
      the levels of all the urinary and serum indexes (P>0.05) and pathological changes
      of the renal tissues. Compared with the normal control group, the contents of
      urinary microglobulin alpha 1, micro-albumin, transferrin and IgG, and serum
      creatinine, urea nitrogen and uric acid were significantly increased in the model
      group (P<0.01). Following medication and moxibustion, the contents of the
      aforementioned 7 indexes in the Losartan group, and urinary microglobulin alpha
      1, micro-albumin, transferrin and IgG, and serum creatinine levels in the
      moxibustion BL 23-20 min and 30 min groups, and the micro-albumin and transferrin
      contents in the BL-17 10 min group and IgG level in the BL-23 10 min group, the
      serum creatinine and urea nitrogen levels at the 3 time-points of both
      moxibustion BL 23 and BL 17 groups, and serum uric acid in the moxibustion BL 23
      30 min, and BL17 20 and 30 min groups were all considerably down-regulated
      (P<0.05, P<0.01). The therapeutic effects of moxibustion 30 min were notably
      better than moxibustion 10 min in reducing urinary microglobulin alpha 1, micro
      albumin, transferring and IgG levels (P<0.05, P<0.01). Results of PAS staining
      showed that the injury of the renal tissue as the endothelial and mesangial
      cellular proliferation, collagen proteinosis, interstitial fibrosis, etc were
      relatively milder in the Losartan and moxibustion 20 and 30 min groups.
      CONCLUSIONS: Mild moxibustion may reduce proteinuria, and improve the kidney
      function and pathological changes in FSGS rats, and longer duration of
      moxibustion is better in achieving therapeutic effect.

PMID- 29071896
TI  - [Effect of Manual Acupuncture Intervention on Levels of 5-HTT, 5-HT1AR, NEalpha2R
      of Brain Tissues in Rats with Post-stroke Depression].
AB  - OBJECTIVE: To observe the effect of manual acupuncture intervention on serotonin
      transporter (5-HTT), 5-HT 1 A receptor (5-HT1AR), norepinephrine (NE) alpha
      receptor 2 (NEalpha2R) protein of brain tissues in rats with post-stroke
      depression (PSD). METHODS: Forty SD rats were randomly divided into normal group,
      model group, medication group and acupuncture group, with 10 rats in each. The
      PSD model was established by the combination of middle cerebral artery occlusion
      and chronic non- predictable mild stress. Rats of the medication group were
      treated by gavage of fluoxetine (2 mg/kg, once daily for 21 days), and those of
      the acupuncture group treated by manual acupuncture stimulation of "Baihui"(GV
      20), "Fengfu" (GV 16), bilateral"Shenmen" (HT 7) and "Taichong" (LR 3) for 20
      min, once a day for 21 days, with one day's interval between each every 7 days.
      The animals' neurological deficit was detected by Zea Longa's scaling, and the
      depression status assessed by sugar solution consumption, and the locomotor
      activity (crossing and rearing times in 5 min) detected by open-field tests. The
      contents of 5-HT, NE, acetylcholine (ACh), gamma aminobutyric acid (GABA), and
      glutamate (Glu) of the cerebral cortex were detected using high performance
      liquid chromatography (HPLC) and expression levels of 5-HTT, 5-HT1AR, NEalpha2R
      proteins of the hippocampus, raphe nuclei and locus coeruleus(LC) tissues
      detected using western blotting (EB), respectively. RESULTS: After modeling, the
      neurological deficit score was significantly increased, while the sugar solution
      consumption and the locomotor activities (crossi-ng and rearing times in 5 min)
      were notably decreased (P<0.05, P<0.001). Findings of HPLC and WB indicated that
      after modeling, the cerebrocortical 5-HT and NE contents and 5-HTT protein
      expression levels in the hippocampus, raphe nucleus and LC were obviously
      decreased and the cortical ACh, GABA and Glu contents as well as the expression
      of 5-HT1AR and NEalpha2R proteins in the hippocampus, raphe nucleus and LC
      considerably increased in the model group (P<0.01). Following acupuncture
      intervention and medication, the increased neurological deficit score, cortical
      ACh, GABA and Glu contents, and the expression le-vels of 5-HT1AR and NEalpha2R
      proteins in the hippocampus, rahpe nucleus and LC, as well as the decreased sugar
      solution consumption, crossing and rearing times of open field tests, cortical 5
      HT and NE contents, as well as cortical 5-HT protein expression were all reversed
      in both acupuncture and medication groups (P<0.05, P<0.01). No significant
      differences were found between the acupuncture and medication groups in all the
      above-mentioned indexes (P>0.05). CONCLUSIONS: Acupuncture can improve the
      locomotor function changes in stroke rats with depression after stroke, which may
      be associated with its effects in suppressing the up-regulated cortical ACh,
      GABA, Glu contents, the expression levels of 5-HT1AR and NEalpha2R proteins in
      the hippocampus, raphe nucleus and LC, and the down-regulated 5-HT and NE
      contents in the cerebral cortex and 5-HTT protein expression levels in the
      hippocampus, raphe nucleus and LC.

PMID- 29071897
TI  - [Characteristics of Deqi Induced by Needling Zusanli (ST 36) in 527 Healthy
      Volunteers with Different Constitutions].
AB  - OBJECTIVE: To explore the relationship between the theory of constitution in
      terms of Chinese medicine and clinical efficacy of acupuncture treatment via
      analyzling the characteristics of Deqi during acupuncture stimulation of Zusanli
      (ST 36) in healthy volunteers with different constitutions. METHODS: In the
      present study, a total of 527 healthy undergraduate student volunteers (267 girls
      and 260 boys) were recruited. They received questionnaire first about their
      constitutions in accordance with Professor WANG Qi's Classification and
      Determination of Constitution in terms of Chinese medicine. Then, the subjects
      were asked to take a supine position on a check-bed, a qualified acupuncturist
      held a sterilized fifiform needle to rapidly insert it into ST 36 and manipulated
      the acupuncture needle with uniform reinforcing-reducing technique at a frequency
      of about 60-90 times/min and an amplitude of 0.3-0.5 cm. The status of Deqi was
      assessed by using visual analogue scale (VAS). RESULTS: Needling sensations
      mainly involve soreness, numbness, heaviness, distension, dull pain and
      propagated sensations along meridian (PSC). During acupuncture stimulation, most
      subjects experienced distension sensation, accounting for 90.3%, followed by
      soreness, accounting for 45.9%. Except for PSC reaction, the rest 5 needling
      sensations had no statistical difference in their occurrence rates in those
      subjects with different constitutions (P>0.05). The PSC appeared a higher
      incidence in yin-yang harmony(balanced) constitution subjects than in qi-
      deficiency, yang-deficiency, blood-stagnation and qi-stagnation constitution
      subjects (P<0.05). The intensity of soreness was obviously stronger in the
      balanced constitution subjects than in qi-deficiency, yang-deficiency, yin
      deficiency, phlegm-damp, damp-heat and qi-stagnation constitution subjects
      (P<0.05), while the intensity of distension sensation was apparently stronger in
      the balanced constitution subjects than in simpleyang-deficiency subjects
      (P<0.05). CONCLUSIONS: Except for PSC, the Deqi sensations of soreness, numbness,
      heaviness, distension and dull pain induced by acupuncture stimulation of ST 36
      are comparable in the occurrence rates in healthy volunteer subjectswith
      different (9 types of) constitutions in terms of Chinese medicine, whereas the
      intensity of soreness may be the important factor for acupuncture induced pain
      relief. A certain correlation between the constitution and acupuncture
      effectiveness exists, suggesting that acupuncture treatment should vary from
      patient to patientin clinical practice.

PMID- 29071898
TI  - [Distribution of Press-sensitive Acupoints in Patients with Tinnitus].
AB  - OBJECTIVE: To explore the regularity of distribution of press-sensitive acupoints
      on the body surface in tinnitus patients, so as to provide evidence for selecting
      suitable acupuncture points in the treatment of tinnitus. METHODS: Sixty-three
      cases of tinnitus patients (from 25 to 75 years in age) were recruited in the
      present study. The patient was asked to take a sitting, supine and prone
      position, successively, and the operator used the thumb to moderately press the
      subject's head, neck, back, four limbs below the knee- and elbow joints along the
      three Hand- and three Foot-yang and yin meridians. Those acupoints that appeared
      pressing pain, or soreness-distension, numbness, or radiation feeling more than
      10 times were brought into the sequence analysis by using the Excel 2010.
      RESULTS: A total of 131 press-sensitive acupoints including 41 points with an
      appea-rance frequency of more than 10 times were found in the 63 tinnitus
      patients. These 41 acupoints distributing in the top three meri-dians were the
      Gallbladder Meridian of Foot-Shaoyang, Tri-energizer Meridian of Hand-Shaoyang
      and Spleen Meridian of Foot-Taiyin, and their involved regions were those below
      the knee-joints, bilateral sides of the head and marginal portion of the ear,
      sites bellow the elbow-joints, back-waist, successively in the appearance
      frequency. The top ten acupoints are Wangu (GB 12), Yifeng (SJ 17), Waiguan (SJ
      5), Quchi (LI 11), Sanyinjiao (SP 6), Yanglingquan (GB 34), Fengchi (GB 20),
      Taichong (LR 3), Shousanli (LI 10) and Zulinqi (GB 41), in sequence. CONCLUSIONS:
      The press-sensitive acupoints in tinnitus patients distribute principally in the
      Gallbladder Meridian of Foot-Shaoyang, and below the knee-joint, and the most
      sensitive acupoints are Wangu (GB 12) and Yifeng (SJ 17). These findings may
      provide an objective basis for clinical diagnosis and treatment of tinnitus.

PMID- 29071900
TI  - [Progress of Researches on Central Mechanism of Electroacupuncture Tolerance].
AB  - Electroacupuncture (EA) has been demonstrated effective for pain relief. However,
      repeated application may decline analgesic effect of EA, which is termed EA
      tolerance, that reduces the clinical efficacy of EA. Therefore, it has attracted
      attention from researchers in recent years and the progresses include:(1) acute
      and chronic EA tolerance animal models have been established; (2) cross-tolerance
      between EA and morphine; (3) Anti-opioid substances, including cholecystokinin,
      orphanin FQ and angiotensin II, have been reported to contribute to EA tolerance;
      (4) glutamate receptors and transporters, 5-hydroxytryptamine and norepinephrine
      have been revealed involvement in EA tolerance; (5) cyclic adenosine
      monophosphate, cyclic guanosine monophosphate and Ca2+ have been reported to be
      the second messengers cellularly in EA tolerance. The current EA tolerance effect
      lacks in-depth researches. Therefore, studies on its molecular mechanisms and
      signaling pathway are necessarily required.

PMID- 29071899
TI  - [Acupoints Selection Exploring for Acupuncture Treatment of Insulin Resistance
      Based on Data Mining].
AB  - OBJECTIVE: To analyze the characteristics and rules of acupoint selection for
      acupuncture treatment of insulin resistance. METHODS: Data collections were
      conducted by searching references on acupuncture treatment of insulin resistance
      in PubMed, CNKI, VIP data base from 1991 to 2016, and acupuncture prescription
      data base for acupuncture treatment of insulin resistance was established. Data
      mining was applied to analyze the characteristics and rules of acupoint
      selection. RESULTS: A total of 64 papers were recruited, and 73 acupoints were
      selected in these papers. It was found that the acupoints as Zusanli (ST 36),
      Sanyinjiao (SP 6), Fenglong (ST 40) and Taichong (LR 3) were used with highest
      frequencies. All acupoints selected distributed in 13 meridians, especially Foot
      Yangming Stomach Meridian, Foot Taiyin Bladder Meridian, and Conception Vessel
      with a total frequency of 58.07%. The special acupoints including five-shu
      points, eight confluent points and back-shu points, accounted for 56.71%.
      CONCLUSIONS: This study excavated the regular acupoint selection and acupoints
      compatibility for acupuncture treatment in patients with insulin resistance,
      giving evidence based confirming and direction for acupuncture clinical
      treatment.

PMID- 29071901
TI  - [An Introduction to A Newly-developed "Acupuncture Needle Manipulation Training
      evaluation System" Based on Optical Motion Capture Technique].
AB  - In the present paper, the authors introduce a newly-developed "Acupuncture Needle
      Manipulation Training-evaluation System" based on optical motion capture
      technique. It is composed of two parts, sensor and software, and overcomes some
      shortages of mechanical motion capture technique. This device is able to analyze
      the data of operations of the pressing-hand and needle-insertion hand during
      acupuncture performance and its software contains personal computer (PC) version,
      Android version, and Internetwork Operating System (IOS) Apple version. It is
      competent in recording and analyzing information of any ope-rator's needling
      manipulations, and is quite helpful for teachers in teaching, training and
      examining students in clinical practice.

PMID- 29071903
TI  - [Exploration on Whether to Standardize Acu-moxibustion].
AB  - Acu-moxibustion is the important component and inseparable in Chinese medicine
      with its unique characteristics. Just due to the distinct characteristics of acu
      moxibustion, whether to standardize acu-moxibustion has been highlighted among
      the people in consideration of its development. In the present paper, the author
      introduces the characteristics of acu-moxibustion, the existence situation of its
      characteristics after being standardized, and the function, substance,
      feasibility, practice and effect, plan and strategy of acu-moxibustion
      standardization.

PMID- 29071902
TI  - [From Treatment of Stress Disease by Acupuncture to Correlation between
      Acupuncture and Stress].
AB  - Stress disease is a body functional disorder caused by harmful stimuli
      overwhelming the nonspecific adaptive capabilities. Numerous evidence proved the
      feasibility of acupuncture in treating stress diseases. This paper aims at
      exploring new perspective in the study on the underlying mechanism of acupuncture
      in the treatment of stress diseases. The discussion is conducted by summarizing
      the pathogenesis of stress diseases and mechanisms of its treatment with
      acupuncture, in exploring the related factors of acupuncture and stress response,
      and the correlation between the two from the regulatory pathway, medium,
      characteristics and manifestations.

PMID- 29071905
TI  - [Electroacupuncture at "Zusanli" (ST 36) Alleviates Myocardium Damage in
      Intestinal Ischemia-reperfusion Rats by Up-regulating Periphery Dopamine Level].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36)
      on myocardium ischemic damage following intestinal ischemia-reperfusion (I/R) in
      rats. METHODS: Thirty SD rats were randomly divided into five groups:sham, I/R-1
      h, I/R-4 h, EA-I/R-1 h and EA-I/R-4 h (n=6 in each group). The intestinal I/R
      model was established by occlusion of the superior mesenteric artery. EA (2
      Hz/100 Hz, 2-3 mA) was applied to bilateral ST 36 for 30 min. In rats of the sham
      group, only the stomach was opened. Plasma dopamine (DA) and tumor necrosis
      factor (TNF)-alpha contents, and myocardial myeloperoxidase (MPO) activity and
      methane dicarboxylic aldehyde (MDA) content were assayed using ELISA, and plasma
      creastine kinase isoenzyme (CK-MB) and lactate dehydrogenese (LDH) activities
      were detected using a fully biochemical analyser. Myocardial pathological changes
      were observed under microscope after H.E. staining. RESULTS: Compared with the
      sham group, plasma DA content was significantly decreased in both I/R-1 h and I/R
      4 h groups, while plasma TNF-alpha content and CK-MB and LDH activities, and
      myocardial MPO activity and MDA content in both I/R-1 h and I/R-4 h groups were
      obviously increased (P<0.05). After EA, the decreased plasma DA and the increased
      plasma TNF-alpha contents and the increased plasma CK-MB and LDH and myocardial
      MPO activities and MDA contents in the EA-I/R-1 h and EA-I/R-4 h groups were
      reversed (P<0.05). The inhibitory rates of EA on myocardial MDA content and MPO
      activity were 9% and 13% in the EA-I/R-1 h group and 30% and 15% in the EA-I/R-4
      h group, respectively, suggesting a better protective effect of EA intervention
      on myocardium in the EA-I/R-4 h group. CONCLUSIONS: EA of ST 36 has a better
      protective action on myocardium in intestinal I/R injury rats, which may be
      related to its effects in up-regulating plasma DA level and down-regulating
      circulating pro-inflammatory factor TNF-alpha content, and reducing myocardial
      oxygen free radicals.

PMID- 29071904
TI  - [Does the Nucleus Ambiguus-Vague Nerve Mediate Anti-myocardial Ischemic Effect of
      Electroacupuncture of "Neiguan" (PC 6)-"Jianshi" (PC 7) in Myocardial Ischemia
      Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Neiguan" (PC 6)-"Jianshi" (PC 7) on ischemic myocardial injury in myocardial
      ischemic (MI) rats, so as to explore its mechanism underlying improvement of MI.
      METHODS: A total of 48 male Wistar rats were randomly divided into normal, MI
      model, PC 6-PC 7, Sanyinjiao-Diji (SP 6-SP 8) groups (n=8 in each group for
      physiological experiments, n=4 in each group for immunoflorescence stain). The MI
      model was established by occlusion of the anterior descending branch of the left
      coronary artery. Electrocardiogram (ECG) of the neck-thoracic lead was recorded
      and the heart rate variability (HRV) analyzed by using a physiological signal
      collecting system (MP 150) and PowerLab software. EA (2 Hz/15 Hz, 0.5 mA) was
      applied to bilateral PC 6-PC 7 or SP 6-SP 8 for 30 min every time, on the 1,2,3
      day after modeling. Serum creatine kinase-MB isoenzyme (CK-MB) and lactate
      dehydrogenase-1 (LDH 1) and endothelin (ET) contents were assayed by ELISA. The
      expression of choline acetyltransferase (ChAT) and vesicular acetylcholine
      transporter (VAChT) and c-fos proteins in the nucleus ambiguus (NA) region of the
      medulla oblongata was detected by immunofluo-rescence stain. RESULTS: Compared
      with the normal group, the ECG J-point height (1 h), serum CK-MB, LDH 1 and ET
      contents (1 d and 3 d), HR (1 h and 1 d) and LF/HF levels of HRV (1 h, 1 d and 3
      d) and the number of c-fos positive neurons (3 d) in the NA region were
      significantly increased in the model group (P<0.01, P<0.05), while HF levels (1
      h, 1 d and 3 d) and ECG J-point height (1 d and 3 d) were considerably decreased
      after MI. After EA intervention, the ECG J-point height 3 d after MI was close to
      zero in both PC 6-PC 7 and SP 6-SP 8 groups, being better than that (negative
      value) of the model group, and serum CK-MB, LDH 1 and ET contents (1 d, 3 d) of
      both EA groups, and HR (1 d) and LF/HF (3 d) of the PC 6-PC 7 group were
      obviously down-regulated (P<0.01, P<0.05), and the decreased HF 3 d post-MI and
      the increased number of c-fos positive neurons were significantly up-regulated in
      the PC 6-PC 7 group (P<0.01). No significant differences were found between the
      two EA groups in raising J-point height and in down-regulating serum CK-MB, LDH 1
      and ET contents (P>0.05). Compared with the model group, no significant changes
      were found in HR 1 d post-MI of the SP 6-SP 8 group, 3 d post-MI of both EA
      groups, in HF 3 d post-MI of the SP 6-SP 8 group, in LF/HF 1 d post-MI of both EA
      groups and 3 d post-MI of the SP 6-SP 8 group, in the number of c-fos positive
      neurons of the SP 6-SP 8 group, and ChAT and VAChT positive neurons of both EA
      groups (P>0.05). CONCLUSIONS: EA intervention may improve ischemic myocardial
      injury in MI rats, probably by activating neurons in the NA region, and enhancing
      the cardiac parasympathetic tension, and balancing cardiac
      sympathetic/parasympathetic nerve activities, but the effect of cholinergic
      neurons of NA needs being studied further.

PMID- 29071906
TI  - [Effect of Electroacupuncture at Distal and Proximal Acupoints on Expression of
      Spinal p 38 Mitogen-activated Protein Kinase and Cyclic Adenosine 3',5'
      monophosphate in Rats with Lumbago].
AB  - OBJECTIVE: To observe the influence of Electroacupuncture (EA) stimulation of
      different distal-proximal acupoints combination groups on pain reaction, spinal p
      38 mitogen-activated protein kinase (p 38 MAPK) expression and cyclic adenosine
      3', 5'-monophosphate (cAMP) content in experimental lumbago rats. METHODS:
      Seventy-eight male SD rats were randomized into normal, model, sham operation, EX
      B 2-BL 25 (proximal acupoints, PA), BL 40-BL 60 (distal acupoints, DA) and DA+PA
      groups. The lumbago model was established by implanting the autologous nucleus
      pulposus to the site close to the left L 5 dorsal root ganglion and the surface
      of dura mate of spinal cord. EA (2 Hz/100 HZ,1-3 mA) was applied at bilateral EX
      B 2-BL 25 or BL 40-BL 60 or both for 20 minutes, once daily for 7 days. The
      mechanical pain threshold was measured, and the expression of p 38 MAPK in the
      lumbar spinal cord was detected by immunohistochemistry and Western blot,
      separately. The content of cAMP in spinal cord (L 4-L 6) was measured by enzyme
      linked immunosorbent assay (ELISA). RESULTS: After mode-ling, the mechanical pain
      threshold percentages were significantly decreased on day 3, 5 and 7 (P<0.01),
      and after EA stimulation of DA,PA and DA+PA, the decreased pain threshold was
      significantly increased at the 3 time-points (P<0.01), and the effects of both PA
      and DA+PA were markedly superior to that of DA (P<0.05, P<0.01). Following
      modeling, lumbar spinal p 38 MAPK immunoactivity and protein expression, and cAMP
      content were obviously up-regulated (P<0.01). Compared with the model group, the
      levels of p 38 MAPK immunoactivity and protein expression in the 3 EA groups and
      the sham group, and cAMP contents in both PA and DA+PA groups (not in the DA and
      sham groups) were considerably down-regulated (P<0.01, P<0.05). CONCLUSIONS: EA
      stimulation of distal+proximal acupoints and proximal acupoints near the focus
      can raise pain threshold in lumbago rats, which may be associated with their
      effects in suppressing lumbago-induced increase of expression of spinal p 38 MAPK
      protein and cAMP content. The effects of EA of distal+proximal acupoints and
      proximal acupoints are better than those of EA of simple distal acupoints.

PMID- 29071907
TI  - [Effect of Moxibustion and Electroacupuncture on Th 1/Th 2 Immune Balance in Rats
      with Experimental Colitis].
AB  - OBJECTIVE: To observe the effect of moxibustion and electroacupuncture (EA)
      stimulation of "Tianshu" (ST 25) and "Qihai" (CV 6) on Th 1/Th 2 immune balance
      in rats with experimental ulcerative colitis (UC). METHODS: The UC rats were
      randomly allocated to model group, moxibustion group and EA group (n=10 in each
      group). Another 10 rats were used as the control group. The UC model was
      established by injection of fresh colonic mucosal tissue-made antigen emulsifier
      (purified mucosal supernate plus complete Freund's adjuvant, 3.5 mg on day one,
      and 7 mg thereafter) into the bilateral toes, inguinal grooves, back, and the
      abdominal cavity on day 1, 10, 17 and 24, respectively. Medicinal paste
      (containing Cortex Cinnamomi,Flos Carthami, etc.)-separated moxibustion or EA
      (200 Hz, 2 mA) was applied to ST 25 and CV 6 for 20 min, once daily for 14 days.
      The mRNA expression levels of interferon-gamma (INF-gamma), IL-12, IL-4 and IL-10
      in colon tissues were detected using quantitative RT-PCR and their content
      determined using enzyme linked immunosorbent assay (ELISA). The colon tissue cell
      ratios of CD 4+ INF-gamma+ and CD 4+ IL-4+ were analyzed by flow cytometry.
      RESULTS: Compared with the control group, the mRNA and contents of colonic INF
      gamma and IL-12 and the ratio of CD 4+ INF-gamma+ and CD 4+ IL-4+ were
      significantly higher in the model group (P<0.05), and the IL-4 and IL-10 mRNA
      expression and contents considerably lower after UC modeling (P<0.05). Following
      medicinal paste-separated moxibustion and EA interventions, the increased INF
      gamma and IL-12 mRNA and contents and the increased ratio of CD 4+ INF-gamma+ and
      CD 4+ IL-4+, and the decreased IL-4 and IL-10 mRNA and contents were reversed
      (P<0.05). No significant differences were found between the moxibustion and EA
      groups in the levels of all the indexes (P>0.05). CONCLUSIONS: Both medicinal
      paste-separated moxibustion and EA interventions may regulate the balance between
      Th 1 and Th 2 cells in the colonic tissues of UC rats, suggesting an improvement
      of the immune function by down-regulating INF-gamma and IL-12 levels and up
      regulating IL-4 and IL-10 levels.

PMID- 29071908
TI  - [Effect of Electroacupuncture Intervention on Inflammatory Reactions and
      Articular Synovial TNF-alpha Converting Enzyme Protein/NF-kappaB Signaling in
      Rheumatoid Arthritis Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on
      inflammatory reactions and articular synovial nuclear factor kappa B (NF-kappaB)
      and TNF-alpha converting enzyme (TACE) protein expression in rheumatoid arthritis
      (RA) rats, so as to elucidate its anti-inflammatory mechanism. METHODS: Forty
      Sprague-Dawley (SD) rats were randomly divided into normal control, model, EA,
      and non-acupoint groups, with 10 rats in each group. The RA model was established
      by intradermal injection of bovine type II collagen emulsified in incomplete
      Freund's adjuvant for 21 days. EA (2 Hz, 1 mA) was applied to bilateral "Zusanli"
      (ST 36), "Xuanzhong" (GB 39) and "Shenshu" (BL 23) for 15 min, once daily for 19
      days, starting from the third day on after modeling. The sham acupoints (5 mm
      lateral to the above-mentioned acupoints) received the same stimulation to EA
      group. Paw swelling volume was detected using a water-filled glass mug, the serum
      C-reactive protein (CRP) and rheumatoid factor (RF) contents were assayed using
      velocity scatter turbidimetric method, and the plasma erythrocyte sedimentation
      rate (ESR) was assayed with Westergren method and VES-MATIC 20 ESR auto-analyzer
      and the expression levels of TACE and NF-kappaB proteins in the synovial tissue
      of knee joint were detected by Western blot. RESULTS: After RA modeling, the hind
      paw volume was significantly bigger in the RA rats than in the normal rats
      (P<0.01), and remarkably lower in the EA group (not in the non-acupoint group)
      than in the model group (P<0.05). In addition, the plasma ESR, serum CRP and RF
      contents and the expression levels of NF-kappaB and TACE proteins in the synovial
      tissues were significantly increased in the model group compared with those in
      the normal group (P<0.01), and were obviously down-regulated in the EA group
      (P<0.05), but not in the non-acupoint group (P>0.05). CONCLUSIONS: EA can
      effectively improve the severity of articular inflammatory swelling and lo-wer
      ESR, serum CRP and RF contents and suppress synovial TACE/NF-kappaB protein
      signaling in RA rats.

PMID- 29071909
TI  - [Analysis on Influencing Factors of Acupoint Injection of Drugs for Improving
      Allergic Rhinitis in Rats].
AB  - OBJECTIVE: To observe the therapeutic effect of acupoint injection of mixture
      solution of lidocaine, dexa-methasone (DX) and transfer factor on symptoms and
      serum histamine contents in allergic rhinitis (AR) rats, so as to differentiate
      the role of acupoint stimulation or drug factor influencing the therapeutic
      effect. METHODS: SD rats were randomized into normal (n=8), model, non-acupoint
      drug injection, acupoint-drug injection and acupoint-saline injection groups
      (n=11 in each group). The AR model was established by intraperitoneal injection
      of suspension of ovalbumin (0.3 mg) and aluminum hydroxide (30 mg), 1 mL, once
      every other day for 7 days, followed by nose-dripping of 5% ovalbumin (50 MUL)
      for other 7 days. The AR scores for rhinocnesmus severity (1-2 points), sneezing
      times (1-3 points) and nasal discharge quantity (1-3 points) were assessed by
      cumulative quantification scoring method. "Yintang" (EX-HN 3) and bilateral
      "Yingxiang" (LI 20) were used for acupoint injection of mixture solution of 1%
      Lidocaine, DX and transfer factor (1:1:1, 0.1 mL/acupoint), once every other day
      for 7 days. The non-acupoints were located at the bilateral sub-costal regions
      and the mid-point between the left "Houhai" (GV 1) and "Huantiao" (GB 30).The
      same dose of saline was injected into the aforementioned acupoints for control.
      Serum histamine content was detected by using ELISA, and the nasal mucosal
      pathological changes were also observed after H.E. stain. RESULTS: After the
      treatment, AR modeling induced increase of symptom scores and serum histamine
      contents were significantly decreased in both acupoint-saline injection and
      acupoint-drug injection groups (P<0.01) but not in the non-acupoint-drug
      injection group (P>0.05), and the effects of acupoint-drug injection were
      markedly superior to those of non-acupoint-drug injection group (P<0.01).
      CONCLUSIONS: Acupoint injection of mixture solution of Lidocaine, DX and transfer
      factor is effective in relieving the allergic symptoms and reducing the nasal
      mucosa inflammation in AR rats, which may be related to its action in suppressing
      histamine releasing, mainly by acupoint stimulation. It suggests that the
      therapeutic effect mainly derives from acupoint-injection stimulation, then the
      injected drugs.

PMID- 29071910
TI  - [Effect of Electroacupuncture Intervention on beta-endorphin Levels of
      Hypothalamus and Spinal Cord Tissues in Rats with Pelmatic Incisional Pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on pain
      thresholds (PT) and contents of beta-endorphin (EP) in the hypothalamus and
      spinal cord, and the expression of 5-HT in the dorsal raphe nucleus(DRN)in rats
      with pelmatic incisional pain, so as to investigate the underlying mechanisms of
      acupuncture in reducing post-operative pain. METHODS: Wistar rats were randomized
      into normal control, model, EA and non-acupoint groups (n=8/group). The pelmatic
      pain model was induced by making an incision (about 1 cm in length, to the fascia
      and muscle layers) from the heel towards the toes. EA (2 Hz, 1.5-2 V) was applied
      to "Zusanli" (ST 36) and "Kunlun" (BL 60) or non-acupoint (about 3 mm beside the
      ST 36 and BL 60) on the affected side for 20 min, once daily for three days. The
      thermal PT and mechanical PT were measured before and after operation and after
      EA. The contents of beta-EP in hypothalamus and L3-S4 spinal cord were detected
      using enzyme linked immunosorbent assay (ELISA) and the expressions of beta-EP in
      hypothalamus and 5-HT in DRN were measured with immunohistochemistry. RESULTS:
      After EA intervention, the markedly decreased mechanical and thermal pain
      thresholds on day 1 and 3 after paw incision were significantly increased in the
      EA group (P<0.05), but not in the non-acupoint group (P>0.05). The hypothalamic
      beta-EP content was significantly higher in the model group than in the normal
      group (P<0.05), and further up-regulated in the EA group (not the non-acupoint
      group) than in the model group (P<0.05). In addition, the hypothalamic beta-EP
      immunoreactive (IR)-positive cell number and 5-HT immunoactivity level in DRN
      were also considerably up-regulated in the EA group (P<0.05) but not in the non
      acupoint group (P>0.05). No significant changes were found in the lumbar spinal
      beta-EP contents in the model, EA and non-acupoint groups (P>0.05). CONCLUSIONS:
      EA stimulation of "Zusanli"(ST 36) and "Kunlun" (BL 60) has an analgesic effect
      in pelmatic incision pain rats, which may be related to its effects in raising
      the level of hypothalamic beta-EP and the expression of 5-HT in DRN.

PMID- 29071911
TI  - [Effect of Electroacupuncture plus Polysaccharide of Gastrodia elata Blume on
      Expression of Nestin and Brain Derived Neurotrophic Factor in the Basolateral
      Amygdala of Focal Cerebral Ischemia Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with
      administration of Polysaccharide of Gastrodia elata Blume (PGB) on stem cell
      proliferation in the basolateral amygdala (BLA) of focal cerebral ischemia (FCI)
      rats. METHODS: A total of 40 Sprague-Dawley rats were randomly divided into
      normal control,model,EA, PGB and EA+PGB groups (n=8 rats in each group). The FCI
      model was established by occlusion of the right middle cerebral artery. EA (2 Hz,
      3 V) was applied to "Baihui" (GV 20) and the left "Zusanli"(ST 36) for 30 min,
      once daily for 14 successive days. Rats of the PGB and EA+PGB groups were given
      with PGB (100 mg/kg) by gastrogavage, once daily, for14 successive days. The Zea
      Longa's method was used to determine the animals' nerurological dysfunction score
      on day 1 and 14. The expressions of Nestin and brain derived neurotrophic factor
      (BDNF) of the right BLA were measured by immunohistochemical staining. RESULTS:
      Following modeling, the neurological score, and the numbers of Nestin- and BDNF
      immunoreaction (IR)-positive cells were significantly increased in the model
      group (P<0.05). Compared with the model group, the neurological scores were
      considerably decreased in the EA, PGB and EA+PGB groups (P<0.05), and the numbers
      of Nestin- and BDNF-IR positive cells were further significantly increased in the
      3 treatment groups (P<0.05), and the effect of EA+PGB was notably superior to
      that of simple EA and simple PGB in down-regulating neurological score and up
      regulating Nestin and BDNF expression (P<0.05). CONCLUSIONS: Both EA and PGB
      interventions can improve FCI rats' neurological function, which may be related
      to their effects in up-regulating the expression of Nestin and BDNF to promote
      the proliferation of neural stem cells in the BLA.

PMID- 29071912
TI  - [Effect of Warm-needle-moxibustion on Behavior Reactions and TNF-alpha and MMP-3
      Contents in Knee Cartilage of Rabbits with Knee Osteoarthritis].
AB  - OBJECTIVE: To observe the effect of warm-needle-moxibustion on behavior changes
      and the levels of tumor necrosis factor-alpha (TNF-alpha) and matrix
      metalloproteinase-3 (MMP-3) in the knee cartilage tissue of rabbits with knee
      osteoarthritis (KOA) so as to explore its mechanisms in relieving KOA. METHODS:
      Thirty male Japanese white rabbits were randomly divided into normal, model and
      treatment groups (n=10 in each group). The KOA model was established by using
      immobilization me-thod. The internal and external "Dubi" (ST 35), "Xuehai" (SP
      10) and "Yanglingquan "(GB 34) were punctured with filiform needles first,
      followed by attaching an ignited moxa column to the handle of each inserted
      needles. The treatment was conducted for 20 min every time, once daily for 4
      weeks. The behavioral scores were assessed according to the pain severity, gait,
      joint motion range and articular swelling severity in reference to the modified
      Lequesne's methods. The TNF-alpha and MMP-3 contents in the knee joint cartilage
      tissue were assayed by radioimmunoassay, and pathological changes of the
      articular cartilage tissue were observed under microscope after sectioning and
      H.E. staining. RESULTS: The Lequesne total score, and the cartilage TNF-alpha and
      MMP-3 contents were significantly increased in the model group than in the normal
      group (P<0.05), and obviously down-regulated after warm-needle-moxibustion
      intervention (P<0.05). Under light microscope, the inflammatory infiltration of
      the articular cartilage and the disordered arrangement of chondrocytes in KOA
      rabbits were improved in the treatment group. CONCLUSIONS: Warm-needle
      moxibustion intervention can improve the motor function of rabbits with KOA,
      which may be related to its effects in reducing the level of TNF-alpha and MMP-3
      in articular cartilage tissue.

PMID- 29071913
TI  - [Effect of Transcutaneous Electrical Acupoint Stimulation on Post-surgical
      Gastrointestinal Function, Autonomic Nerve Activities and Plasma Brain-gut
      Peptide Levels in Patients Undergoing Gastrointestinal Surgery].
AB  - OBJECTIVE: To observe the effect of transcutaneous electrical acupoint
      stimulation (TEAS) on ileus-postope-rative gastrointestinal functions and plasma
      ghrelin, motilin, and gastrin contents, and heart rate variability (HRV) in
      patients undergoing gastrointestinal surgery, so as to explore the interaction of
      vagus-brain-gut peptide. METHODS: A total of 58 patients undergoing elective
      gastrointestinal surgery were randomly assigned to TEAS (n=29) and sham-TEAS
      group (n=29, patients had no subjective sensation to 1 mA TEAS, thus, being
      considered to be sham-TEAS). TEAS (2 Hz/100 Hz, 6-8 mA for LI 4-PC 6, 12-18 mA
      for ST 36-SP 6) was applied to bilateral Hegu (LI 4)-Neiguan (PC 6) from 30 min
      pre-operation to the end of the operation and to bilateral LI 4-PC 6 and Zusanli
      (ST 36)-Sanyinjiao (SP 6) for 30 minutes twice daily in 3 consecutive post
      operative days. ECGs of 12 leads were recorded to analyze different parameters of
      HRV from 2 days before and 4 days after surgery. Plasma ghrelin, motilin and
      gastrin contents were assayed by radioimmunoassay, and the patients' first bowel
      sound, first independent walk, first flatus, first solid food-intake and first
      defecation were recorded to evaluate the recovery state of gastrointestinal
      motility. RESULTS: Postoperative gastrointestinal motility:compared with the sham
      TEAS group, the first bowel sound and the first defecation after surgery appeared
      apparently earlier in the TEAS group (P<0.05), but no significant differences
      were found between the two groups at the time of the first independent walk,
      first flatus and the first solid food-intake in patients undergoing
      gastrointestinal surgery. Plasma brain-gut peptides:the plasma ghrelin and
      motilin contents 4 days post-surgery were significant increased in the TEAS group
      than in the sham-TEAS group (P<0.05). No significant difference was found between
      the two groups in plasma gastrin contents (P>0.05). HRV domains:in comparison
      with pre-surgery, the levels of low frequency (LF) and high frequency (HF) of
      frequency domain (FD) and root mean square of successive differences (rMSSD) of
      the time domain (TD) of HRV 4 days after surgery were significantly decreased in
      the sham-TEAS group (P<0.05), but no significant changes were found in both FD
      and TD domains of the TEAS group 4 days after surgery (P>0.05). Compared with the
      sham-TEAS group, the HF and rMSSD levels were significantly increased in the TEAS
      group 4 days after the surgery (P<0.05). No significant differences were found
      between the two groups in the levels of very low frequency, LF and LF/HF levels
      of FD, and standard deviation of NN (beat-to-beat) intervals, the standard
      deviation of the average NN intervals and the proportion of NN 50 (the number of
      pairs of successive NNs that differ by more than 50 ms) divided by total number
      of NNs of TD. CONCLUSIONS: TEAS can promote gastrointestinal activities (i.e.,
      reducing the time spending of first bowel sound and the first defecation) in
      gastrointestinal surgery patients, which may be related to its effects in up
      regulating ghrelin and motilin contents and parasympathetic activity.

PMID- 29071914
TI  - [Effectiveness of Electroacupuncture of Zigong (EX-CA 1), etc. in Treatment of
      Perimenopausal Syndrome Women].
AB  - OBJECTIVE: To evaluate the curative effect of electroacupuncture(EA) of Zigong
      (EX-CA 1) and Tianshu (ST 25) and acupuncture of Sanyinjiao (SP 6) and Guanyuan
      (CV 4) for perimenopausal syndrome(PMS). METHODS: Fifty-eight PMS patients were
      equally and randomized into acupuncture group and medication group. EA (10 Hz/50
      Hz, 30 min in duration) was applied at Zigong (EX-CA 1) and Tianshu (ST 25) in
      combination with manual acupuncture stimulation of Sanyinjiao (SP 6) and Guanyuan
      (CV 4) by twirling the acupuncture needles with small amplitude and till deqi.
      The treatment was conducted once every other day, three times a week, 8 weeks
      altogether. The patients of the medication group were asked to take estradiol
      valerate (1 mg/time, qd) for 3 weeks, then, to have one week's rest and
      continuously took estradiol valerate(1 mg/d) and medroxyprogesterone 17-acetate
      (8 mg/d) for 10 days. The therapeutic effects were assessed by Menopause Rating
      Scale Questionnaire[MRS, composing of 3 areas:somatic (4 items), psychological(4
      items) and urogenital (3 items) domain]. Serum estradiol (E2), follicle
      stimulating hormone(FSH) and luteotrophic hormone (LH) contents were assayed
      using ELISA. RESULTS: After the treatment, the scores of the MRS and the contents
      of serum FSH and LH were significantly decreased in both the acupuncture and
      medication groups (P<0.01), and serum E2 contents significantly increased in the
      two groups (P<0.01). No significant differences were found between the two groups
      in the total effective rates (P>0.05). Eight weeks' follow-up showed that the MRS
      score of the acupuncture group was significantly lower than that of the
      medication group (P<0.05). Of the two 29 PMS patients in the medication and
      acupuncture groups, 3 (10.3%) and 2 (6.9%) cases were under control, 22 (75.9%)
      and 21 (72.4%) experienced a marked improvement in their symptoms, 3 (10.3%) and
      4(13.8%) were effective, 1 (3.4%) and 2(6.9%) invalid, with the effective rates
      being 96.6% and 93.1%, respectively. Eight weeks' follow-up showed that the long
      term effect of the acupuncture therapy was obviously superior to that of the
      medication (P<0.05) according to MRS score. CONCLUSIONS: Acupuncture therapy is
      effective in relieving clinical symptoms of PMS women by regulating endocrine
      hormones, being similar to medication.

PMID- 29071915
TI  - [Acupuncture Combined with Acupoint Application Improves Symptoms, Daily Life
      Quality and Lung Function in Chronic Obstructive Pulmonary Disease Patients
      during Acute Exacerbation].
AB  - OBJECTIVE: To observe the effect of acupuncture combined with acupoint
      application in the treatment of patients with acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD). METHODS: Sixty-two AECOPD patients were
      randomly divided into medication (control) group and acupuncture+acupoint
      application (test) group (n=31 in each group). Patients of the control group were
      treated with inhalation of Draco Lakemedel AB (Budesonide Powder) for 15-20
      min/time, 2 times/d for 15 d, and those of the test group were treated by
      acupuncture stimulation of Lieque (LU 7), Chize (LU 5), Danzhong (CV 17),
      Fenglong (ST 40), Zusanli (ST 36), and Taixi (KI 3) and application of medicinal
      cake[containing Xingren (Amygdalus Communis Vas), Sangbaipi (Morus alba L.),
      etc.] to bilateral Feishu (BL 13), Tiantu (CV 22), bilateral Shenshu(BL 23) and
      Pishu (BL 20). The lung function[forced expiratory volume in 1 second (FEV 1)%,
      forced vital capacity (FVC), and FEV 1/FVC] was detected using a pulmonary
      detector, the severity scores of symptoms (cough, stethocatharsis, gasp, wheeze,
      short breath, 0-3 points) and daily life quality[Client's Assessment of Treatment
      Scale (CAT, 7 items)] were assessed before and after the treatment. RESULTS:
      After the treatment, the scores of symptoms, life quality (CAT) were
      significantly decreased (P<0.05), while FEV 1% and FEV 1/FVC levels were
      considerably increased (P<0.05) in both groups. The effects of the test group
      were significantly superior to those of the control group in down-regulating
      symptom score and life quality score and raising FEV 1% and FEV 1/FVC levels
      (P<0.05). In addition, of the two 30 cases in the control and test groups, 10 and
      18 patients experienced marked improvement, 16 and 10 were effective, 4 and 2
      failed in the treatment, with the effective rates being 86.66% and 93.33%,
      respectively. The effective rate of acupuncture+acupoint application was
      obviously superior to that of medication (P<0.05). CONCLUSIONS: Acupuncture
      combined with acupoint application is effective in improving the symptoms, life
      quality and lung function in patients with AECOPD.

PMID- 29071916
TI  - [Clinical Efficacy and Safety of Heat-sensitive Moxibustion Therapy for Lumbar
      Disc Herniation:A Meta-analysis].
AB  - OBJECTIVE: To systematically review the effectiveness and safety of heat
      sensitive moxibustion (HSM) therapy in the treatment of lumbar disc herniation
      (LDH). METHODS: Papers of randomized clinical trials (RCTs) concerning the
      effectiveness and safety of HSM therapy for LDH published in both Chinese and
      English before November 17, 2015 were collected from PubMed, EMBase, Cochrane
      library, CNKI, CBM, WanFang Data and VIP databases according to the inclusion and
      exclusion criteria and by using key words of "thermal moxibustion" "heat
      sensitive acupoint" "lumbar intervertebral disc herniation (LIDH)" "lumbar disc
      herniation (LDH)" and "lumbago backache", followed by screening, data extracting
      and methodological quality assessing. Then, the Meta-analysis was performed using
      RevMan 5.3 software. RESULTS: Twenty RCTs were included eventually, containing a
      total of 1 861 cases treated by HSM therapy in the treatment of LDH patients. The
      Meta-analysis shows that the effectiveness and safety of HSM therapy for LDH are
      superior to those of other therapies, which is drawn from total effective rate of
      treatment group[RR=1.13, 95%CI(1.09,1.18), P<0.001], M-JOA score[MD=-3.17, 95%CI(
      3.88, -2.47), P<0.001], M-JOA score difference of various subgroups:daily life
      ability effect difference[MD=1.04, 95%CI(0.44, 1.64), P<0.001], subjective effect
      symptoms difference[MD=0.58, 95%CI (0.23, 0.92),P=0.001], objective effect
      symptoms difference[MD=1.12, 95%CI(0.58, 1.65),P<0.001], VAS score[MD=
      1.17,95%CI(-1.78, -0.57), P<0.001], the recurrence rate[RR=0.54, 95%CI(0.37,
      0.80), P=0.002], and no adverse reactions mentioned in the reported results. The
      sensitivity analysis showed a greater homogeneity in literature and the results
      were stable, but funnel plot analysis showed a publication bias. CONCLUSIONS: The
      HSM therapy is effective and safe in the treatment of LDH patients.

PMID- 29071917
TI  - [Regularities of Acupoint Combinations for Facial Paralysis in Chinese Ancient
      Times Analyzed in Accordance with Modern Complex Network Community Framework
      Partition].
AB  - OBJECTIVE: To analyze the characteristics of acupoint combinations (formula) for
      facial palsy in ancient lite-rature, so as to optimize the related acupoint
      prescriptions in clinical practice. METHODS: The database of ancient acupoint
      prescriptions for facial paralysis was established first after searching and
      collecting the related acu-moxibustion literature (178 categories as monographs,
      specific volumes of a book, etc.) by using key words of "facial palsy" or
      "deviation of the eye and mouth" including Chinese terms of "Diaoxianfeng ()"
      "Wopi ()"and "Kouwo()". The characteristics of acupoint selection were analyzed
      and acupoint prescriptions were optimized using bipartite network community
      structure partition. RESULTS: The results indicated that of the 56 acupoints for
      facial palsy collected in the literature, Shuigou (GV 26), Dicang (ST 4), Jiache
      (ST 6), Hegu(LI 4), Fengchi(GB 20), Zusanli (ST 36), Neiting (ST 44), Tinghui (GB
      2), Chengjiang (CV 24) and Shangguan (GB 3) are the core acupoints in clinical
      application. The acupoints of Dicang (ST 4), Jiache (ST 6), Shuigou (GV 26),
      Fengchi(GB 20), Neiting (ST 44), Hegu (LI 4), Zusanli (ST 36), Lieque (LU 7),
      Shangguan (GB 3) and Erjian (LI 2) are most frequently selected for forming
      prescriptions.The optimized acupoint prescriptions are composed of Tinghui (GB
      2), Fengchi (GB 20), Fengshi (GB 31), Xuanzhong (GB 39), Dicang (ST 4), Jiache
      (ST 6), Zusanli (ST 36), Dazhui (GV 14), Baihui (GV 20), Quchi (LI 11) and Jianyu
      (LI 15). Core acupoints were mainly distributed on the Stomach Meridian of Foot
      Yangming, Large Intestine Meridian of Hand Yangming and the Governor Vessel.
      Acupoints at the face and head are used more frequently than those in any other
      parts of the body. Specific acupoints are used more frequently than non-specific
      acupoints, among which Conf-luent Acupoints are most frequently used.
      CONCLUSIONS: In the treatment of facial paralysis in ancient China, selection of
      local acupoints is the basic principle and some specific acupoints are the core
      acupoints in ancient acupuncture prescriptions.

PMID- 29071918
TI  - [Development of Researches on Mechanisms of Acupuncture Intervention in Improving
      Myocar-dial Ischemia by Balancing Interaction between beta-adrenergic Receptor
      and Acetylcholinergic Receptor Signal Transduction Pathway of Myocardiocytes].
AB  - The imbalance of autonomic nervous function after myocardial ischemia (MI)
      accelerates the development of ischemic myocardial injury. The beta-adrenergic
      receptor (beta-AR) and muscarinic acetylcholine receptor (M-AChR) are the main
      receptor types of the cardiomyocyte and the binding sites of the cardiac
      sympathetic and parasympathetic transmitters. In the present paper, the authors
      review recent progress of experimental researches on the mechanisms of
      acupuncture therapy in the prevention and treatment of MI, mainly focusing on the
      signaling of beta1-AR and M2-AChR subtypes. Results showed that acupuncture could
      attenuate the injury of myocardial ischemia via down-regulating the over
      expression of beta1-AR and up-regulating the expression of M2-AChR protein.
      Correspondingly, acupuncture intervention could reverse the abnormal expression
      of the intracellular stimulatory G protein and inhibitory G protein caused by MI,
      and suppress the activity of cellular adenylate cyclase. In addition, acupuncture
      could also enhance the activity of nitric oxide synthase and the level of nitric
      oxide in the ischemic cardiomyocytes, and increase the synthesis of cyclic
      guanosine monophosphate, ultimately reducing the level of cyclic adenosine 3',
      5'monophosphate, and lowering the activity of protein kinase A and the inward
      flow of Ca2+ in cardiomyocytes. In this way, the ischemic myocardial injury is
      improved at last. However, some results of acupuncture intervention are not
      identical and need being confirmed further by more approaches.

PMID- 29071919
TI  - [Progress of Researches on Protective Effect of Acupuncture and Moxibustion in
      Relieving Intracellular Calcium Overload of Cradiomyocytes].
AB  - Myocardial contraction and relaxation are regulated by increases and decreases of
      the intracellular cytoplasmic calcium (Ca2+) concentration. Intracellular calcium
      ion is also a ubiquitous second messenger, and its related signal transduction
      pathways involve a variety of physiological activities and pathological changes.
      It has been well documented that intracellular calcium overload is involved in
      myocardial cellular injury. In the present paper, the authors make a review about
      experimental researches on the underlying mechanisms of acupuncture and
      moxibustion in the prevention and treatment of ischemic myocardial injury from
      reducing calcium overload in recent 10 years. Results of recent studies indicate
      that acupuncture and moxibustion interventions have a cardioprotective effect by
      raising Ca2+-ATPase activity and nitric oxide content, lowering L-type voltage
      depen-dent calcium channel activity, and ameliorating calcium overload in
      ischemic cardiomyocytes mainly through cytomembrane, sarcoplasmic reticulum
      membrane and mitochondrial membrane pathways. However, the current studies on the
      mechanisms of acupuncture in the improvement of the ischemic myocardial injury
      are far unclear up to now and do not closely combine the clinical application.

PMID- 29071920
TI  - [A Systematical Review of Researches on Oxygen Specificity in the Acupoint Area].
AB  - Oxygen, an important substance for metabolism, and its related nitric oxide (NO)
      and carbon dioxide (CO2) play a key role in regulating physiological activities.
      The study on the characteristics of oxygen in the acupoint region has been being
      conducted for nearly 30 years. In the present paper, the authors review recent
      development of researches on changes of partial oxygen pressure (PO2), NO, and
      CO2 levels in the acupoint regions. Some researches demonstrated that the PO2,
      CO2 and NO contents are relatively higher in some acupoints as Zusanli (ST 36),
      etc. in comparison with the neighbor tissues or non-acupoints under normal and
      pathological states in severe infection patients and rats. After acupuncture
      stimulation, CO2 and NO contents were increased, while PO2 content was increased
      or lowered in some acupoints not in non-acupoints. However, there were also some
      arguments about the conclusions of acupoint oxygen specificity. In order to
      verify the results of acupoint oxygen specificity researches, more attentions
      should be paid to the precise experimental design, repeatable experimental
      conditions, homogeneity of subjects, human body observation, Deqi effect of
      acupuncture needle manipulation, etc. in the future studies.

PMID- 29071921
TI  - [Effects of Transcutaneous Electrostimulation of Auricular Points on Behavior and
      Hippocampal IL-1 beta and TNF-alpha Expression in Temporal Lobe Epilepsy Rats].
AB  - OBJECTIVE: To observe the effect of transcutaneous otopoint electrostimulation
      (TCOES) on behavior and expression of hippocampal interleukin-1 beta (IL-1 beta)
      and tumor necrosis factor-alpha (TNF-alpha) expression in lithium-pilocarpine
      induced chronic spontaneous temporal lobe epilepsy (TLE) rats, so as to
      investigate its antiepileptic mechanism. METHODS: Thirty-six SD rats were
      randomly divided into control, model and TCOES groups (n=12 in each group). The
      epilepsy model was established by intraperitoneal injection of lithium chloride
      (127.2 mg/kg), scopolamine(1 mg/kg, 20 h after the 1st injection) and pilocarpine
      (10 mg/kg, 30 min after scopolamine injection). Rats of the control group were
      treated by injection of normal saline(i.p.i.). Transcutaneous electrostimulation
      (1 mA, 20 Hz) was applied to bilateral otopoints "Heart" "Lung" and "Subcortex"
      for 20 min, once daily for 6 weeks except the weekends. The behavior reactions
      were observed by a video monitoring system. The expression of IL-1 beta and TNF
      alpha proteins and genes in the hippocampus were determined by immunofluorescence
      and quantitative real-time PCR, separately. RESULTS: Behavioral observation
      showed that after TCOES intervention, the frequency of epilepsy attack was
      significantly decreased in comparison with pre-treatment (P<0.05).
      Immunofluorescence and real-time PCR showed that compared with the control group,
      the immunoactivity of IL-1 beta and TNF-alpha in both hippocampal CA 1 and CA 3
      regions and hippocampal IL-1 beta and TNF-alpha gene expression were obviously
      increased in the model group (P<0.05, P<0.01). Following TCOES, the increased
      hippocampal IL-1 beta and TNF-alpha and IL-1 beta mRNA and TNF-alpha mRNA
      expression levels were all suppressed (P<0.05, P<0.01). CONCLUSIONS: TCOES
      intervention has an antiepileptogenic effect in temporal lobe epilepsy rats,
      which may be related to its effects in down-regulating expression of
      proinflammatory cytokine IL-1 beta and TNF-alpha in the hippocampus.

PMID- 29071922
TI  - [Effect of Electroacupuncture and Moxibustion on Visceral Pain and Expression of
      VR 1 and HSP 70 of "Tianshu" (ST 25) Region in Colorectal Distension-induced
      Visceral Hypersensitivity Rats].
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) and moxibustion
      (Moxi) on visceral pain and expression of vanilloid receptor subtype 1 (VR 1) and
      heat shock protein (HSP)70 in "Tianshu" (ST 25) region in colorectal distension
      (CRD)-induced visceral hypersensitivity (VHS) rats. METHODS: Fifty male SD rats
      were randomly divided into normal control, VHS model, 43C-moxi, 46C-moxi, 1 mA-EA
      and 3 mA-EA groups (n=10 in each group). The VSH model was established by CRD
      once daily for 14 days. EA or Moxi stimulation was applied to bilateral "Tianshu"
      (ST 25) for 10 min, once daily for consecutive 10 days. The abdominal withdrawal
      reflex (AWR) scores (0-4 points) were rated according to Al-Chaer's and
      coworkers' standards (2000) and the expression levels of VR 1 and HSP 70 in
      bilateral ST 25 area tissues detected by immunohistochemistry. RESULTS: The AWR
      scores for 20, 40, 60 and 80 mmHg CRD pressures were significantly increased
      compared to the normal control group (P<0.01) and notably decreased after 43C-
      and 46C-moxi, and 1 mA- and 3 mA-EA stimulation of bila-teral ST 25 in comparison
      with the model group (P<0.05, P<0.01), and the effect of 46C-moxi was apparently
      superior to those of 1 mA-EA at 40 and 80 mmHg, and 3 mA-EA at 40 mmHg (P<0.05).
      After modeling, the expression of both VR 1 and HSP 70 (percentages of area of
      positive-cells) in ST 25 region had no significant changes (P>0.05). Compared to
      the model group, the expression levels of VR 1 in the 43C-moxi and 46C-moxi
      groups, and HSP 70 in the 43C-moxi and 46C-moxi, 1 mA-EA and 3 mA-EA groups were
      significantly up-regulated (P<0.01), but without obvious changes in the
      expression of VR 1 in the 1 mA-EA and 3 mA-EA groups (P>0.05). The effects of 46C
      moxi were considerably better than those of 43C-moxi, 1 mA-EA and 3 mA-EA in up
      regulating VR 1 and HSP 70 expression (P<0.05, P<0.01). No significant
      differences were found among the 43C-moxi, 1 mA-EA and 3 mA-EA groups in the
      expression of VR 1 and HSP 70 (P>0.05). CONCLUSIONS: Moxibustion at 43C and 46C
      and EA at 1 mA and 3 mA, especially the 46C-moxi, can relieve visceral pain in
      visceral hypersensitivity rats, which may be related to their effects in up
      regulating expression of VR 1 and HSP 70 in "Tianshu" (ST 25) area.

PMID- 29071923
TI  - [Distribution of Substance P-positive Nerve Fibers in Local Skin Tissues of Five
      Shu-points of the Pericardium Meridian in the Rat].
AB  - OBJECTIVE: To investigate the distribution of substance P (SP)-positive nerve
      fibers in local skin tissues of the five shu-points of the Pericardium Meridian
      in rats for revealing the differential innervations of the five acupoints.
      METHODS: Six adult male SD rats were used in the present study. Under deep
      anesthesia, the rats received transcardiac perfusion with 4%
      polyformaldehyde+phosphate buffered solution, followed by dissecting the local
      skin tissues from the sites corresponding to five shu-points "Zhongchong" (PC 9),
      "Laogong" (PC 8), "Daling" (PC 7), "Jianshi" (PC 5), and "Quze" (PC 3) in the
      human body. The tissues were sagittally cut into sections (20 MUm) using a
      freezing microtome, followed by fluorescent immunohistochemi-cal and
      histochemical staining with SP, phalloidin and DAPI, respectively. The
      distribution of SP-positive fibers were observed under fluorescent microscope and
      laser confocal microscope. RESULTS: In general, SP expressed on the thin sensory
      fibers in the skin tissue. SP-positive nerve fibers distributed in a free single
      style in the epidermis and dermis, and gathered together to form a bundle in the
      subcutaneous layer. After counting the number and length of free single fibers in
      the epidermis and dermis of each of the five shu-points, we found that no
      significant differences existed in the density between the PC 9 and PC 8 regions,
      as well as among the PC 7, PC 5, and PC 3 regions (P>0.05). In contrast, the
      density of SP-positive nerve fibers in the former two acupoints (PC 9 and PC 8)
      was significantly higher than that of anyone of the latter three acupoints
      (P<0.01). In addition, SP positive nerve fibers mainly ran in parallel to the
      vessel-like structure. CONCLUSIONS: The local skin tissues of acupoint PC 9, PC
      8, PC 7, PC 5, and PC 3 of the Pericardium Meridian express SP-positive fibers,
      which presents a decreasing tendency in the density from the distal to the
      proximal part of the forelimb, reflecting a relative specificity of the
      innervations of the five shu-points.

PMID- 29071924
TI  - [Influence of Heat-reinforcing Needling on Expression of Plasma Atp 5 O mRNA and
      Atp 6 V 1 B 2 mRNA in Patients with Rheumatoid Arthritis of Wind-cold-damp
      Retention Type].
AB  - OBJECTIVE: To observe influences of heat-reinforcing needling (HRN) on scores of
      traditional Chinese medicine (TCM) symptoms and expression of plasma ATP synthase
      subunit O (Atp 5 O) mRNA and lysosomal V 1 subunit B 2 (Atp 6 V 1 B 2) mRNA in
      patients with wind-cold-damp retention type rheumatoid arthritis (RA), so as to
      investigate its biological mechanisms in "heat production". METHODS: Sixty wind
      cold-damp retention type RA patients were randomly allocated to HRN group (n=30)
      and control group (n=30). Guanyuan (CV 4), Qihai (CV 6), bilateral Zusanli (ST
      36), and local acupoints near the knee-joint were selected for needling
      stimulation. Patients of the HRN group were treated by manipulating the
      acupuncture needle with HRN, and those of the control group treated by
      manipulating the needle with uniform reinforcing-reducing method. The treatments
      were performed once daily, 5 days a week, and two weeks altogether. The other 30
      healthy volunteers were recruited as the normal control group. The TCM symptom
      scoring system (0-31 points, 11 items as the severities of pain, swelling and
      tenderness of the knee-joint) was used to evaluate the status of RA, and
      quantitative real-time PCR (RT-PCR) was used to detect the expression of plasma
      Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA following removal of red blood cells.
      RESULTS: After the treatment, the TCM scores of both the HRN and control groups
      were significantly decreased (P<0.05), and that of the HRN group was
      significantly lower than that of the control group (P<0.05). Before the
      treatment, the expression levels of plasma Atp 5 O mRNA and Atp 6 V 1 B 2 mRNA in
      RA patients were significantly lower than those of the normal group (P<0.05), and
      after the treatment, the expression levels of plasma Atp 5 O mRNA and Atp 6 V 1 B
      2 mRNA were significantly increased in both HRN and control groups compared to
      pre-treatment in the same one group (P<0.05), and the up-regulated Atp 5 O mRNA
      and Atp 6 V 1 B 2 mRNA levels were remarkably higher in the control group than in
      the HRN group (P<0.05). CONCLUSIONS: Both heat-producing needling and uniform
      reinforcing-reducing needling can improve RA patients' clinical symptoms, which
      may be associated with their actions in up-regulating expressions of plasma Atp 5
      O mRNA and Atp 6 V 1 B 2 mRNA.

PMID- 29071925
TI  - [Effects of Electroacupuncture on Hippocampal nNOS Expression in Rats with
      Anxiety-like Behavior].
AB  - OBJECTIVE: To compare the effects of electroacupuncture (EA) preconditioning and
      post-conditioning on hippocampal neuronal nitric oxide synthase (nNOS) expression
      in rats with anxiety-like behavior, so as to explore the reasonable EA
      intervention time. METHODS: Forty-two SD rats were randomly divided into 6
      groups:normal 1, normal 2, anxiety model 1, an-xiety model 2, EA-pre-conditioning
      and EA-post-conditioning. The anxiety model was established by giving the rats
      with repeated foot shock stimulation (0.8 mA, 2-25 s/time, 10 times in 5 min)
      combined with isolation-raising. Before or after modeling, EA stimulation was
      applied to "Baihui" (GV 20) and "Yintang" (GV 29) for 20 min, once a day for 7
      days. Elevated plus maze (EPM) tests were performed to determine the percentages
      of time spent in the open arms and the percentages of entries into the open arms
      in 5 min for evaluating the animals' anxiety-like behavioral activities. The
      reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect
      hippocampal nNOS mRNA expression and the immunohistochemical staining adopted to
      detect the expression of nNOS protein in the hippocampal CA 1 and CA 3 areas,
      respectively. RESULTS: Compared with their own normal control group 1 and 2, both
      the percentage of time spent in the open arms and the percentage of entries into
      the open arms were significantly decreased in model group 1 and 2 (P<0.05,
      P<0.01). After pre- and post-conditioning of EA, the decreased proportions of
      time spent and entries into the open arms were considerably increased (P<0.05),
      suggesting an improvement of anxiety-like behavior activities after EA
      intervention. The expression levels of hippocampal nNOS mRNA and nNOS protein in
      the hippocampal CA 3 region were significantly higher in the model group 1 and 2
      than in their own normal control group 1 and 2 (P<0.01), but those of nNOS
      protein in the CA 1 area were markedly lower in the model group 1 and 2 than in
      their own normal control group 1 and 2 (P<0.01). Following pre- and post
      conditioning of EA, the increased expression levels of nNOS mRNA and protein of
      CA 3 area and the decreased level of nNOS protein of CA 1 area were all notably
      reversed (P<0.05, P<0.01). CONCLUSIONS: Both pre- and post-conditioning of EA can
      improve anxiety-like behavior in anxiety rats, which may be associated with its
      effects in down-regulating hippocampal nNOS expression.

PMID- 29071926
TI  - [Effect of Electroacupuncture Combined with Rehabilitation Training on
      Neurological Function and Expression of Neuronal Growth Associated Protein 43 and
      Synaptophysin in Rats with Focal Cerebral Ischemia/Reperfusion Injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with
      rehabilitation training on motor function and expression of neuronal growth
      associated protein 43 (GAP-43) and synaptophysin (SYP) in hippocampal CA 3 region
      in rats with focal cerebral ischemia/reperfusion injury (CI/RI). METHODS: A total
      of 46 SD rats were randomized into normal control, CI/RI model, rehabilitation
      training (RT), paralysis-side (unilateral)-EA+RT, and bilateral-EA+RT groups (n=6
      in the normal control group, and n=10 in each of the other group). The CI/RI
      model was established by occlusion of the middle cerebral artery (MCAO) and
      reperfusion. EA (5 Hz/10 Hz, 2 mA) was applied to the unilateral "Quchi" (LI 11)
      and "Housanli" (ST 36) on the affected side or bilateral LI 11 and ST 36 for 30
      min, once daily for two weeks except the Sunday. The neurological deficit
      severity (Zea Longa score) was assessed 24 h, 7 and 14 days after modeling. The
      immunoactivity of GAP-43 and SYP in the CA 3 region of the hippocampus was
      detected using immunohistochemistry. Pathological changes of the prefrontal
      cortex was observed after H.E. staining. RESULTS: Following modeling, the
      neurological deficit scores of the model, RT, unilateral-EA+RT and bilateral
      EA+RT groups were gradually decreased, and were significantly lower on day 7 and
      14 in the bilateral-EA+RT group and on day 14 in the unilateral-EA+RT group than
      in the model group (P<0.05). The effect of the bilateral-EA+RT group was
      obviously superior to those of both RT and unilateral EA+RT groups in improving
      neurological function (P<0.05). Results of immunohistochemical staining displayed
      that the expression levels of GAP-43 and SYP in the CA 3 region of hippocampus
      were significantly up-regulated in the model group than in the normal control
      group (P<0.05), and further obviously up-regulated in both unilateral-and
      bilateral-EA+RT groups (P<0.05). No significant changes of GAP-43 and SYP protein
      expression in the RT group compared with the model group (P>0.05), and the
      expression levels of GAP-43 and SYP protein in the bilateral-EA+RT were
      significantly higher than those in the unilateral EA+RT group (P<0.05). H.E.
      staining showed that the ischemic injury of cells (neuronal apoptosis and
      enlargement of intercellular space) of the prefrontal cortex was relatively
      milder in the EA+RT groups. CONCLUSIONS: EA plus RT can promote the recovery of
      motor function in CI/RI rats, which may be associated with its function in
      increasing the expression of GAP-43 and SYP in hippocampal CA 3 region. The
      effects of bilateral-EA+RT is obviously better than those of unilateral EA+RT.

PMID- 29071927
TI  - [Effects of Direct Moxibustion of "Ganshu"(BL 18) on the Contents of T cells in
      Peripheral Blood in Rats with Precancerous Lesion of Primary Hepatocellular
      Carcinoma].
AB  - OBJECTIVE: To observe the effect of moxibustion stimulation of "Ganshu"(BL 18)
      region on contents of T cells in the peripheral blood in rats with
      Diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC), so as to explore
      its effective in improving immunoregulatory function. METHODS: Seventy male
      Wistar rats were randomly divided into control group (n=10), model group(n=15),
      direct moxibustion-15 s group(n=15), direct moxibustion-30 s group (n=15) and
      ginger-separated moxibustion group(n=15). The primary HCC precancerous lesion
      model was established by intraperitoneal injection of DEN (50 mg/kg), once every
      3 days for 10 weeks. Moxibustion was applied to bilateral "Ganshu"(BL 18) for
      about 15 min (3 moxa-cones), or 30 min (six moxa-cones), with or without ginger
      slice separation, once every other day for 10 consecutive weeks. The contents of
      T cells of CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ ratio in the peripheral blood were
      detected with Flow Cytometey(FCM), pathological changes of liver were observed by
      light microscope after hematoxylin-eosin(HE) stain. RESULTS: Compared to the
      control group, the contents of blood CD 3+ and CD 4+ T cells and ratio of CD
      4+/CD 8+ were significantly down-regulated, while that of CD 8+T cells was
      obviously increased in the model group(P<0.05,P<0.01). After moxibustion
      intervention, the decreased CD 3+ and CD 4+T cells and CD 4+/CD 8+ levels and the
      increased CD 8+T cell contents were reversed in all the 3 moxibustion groups
      (P<0.05, P<0.01), except CD 3+ in the ginger-separated moxibustion group
      (P>0.05). There were no significant differences among the three moxibustion
      groups in the CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ levels (P>0.05). In addition,
      the pathological changes of liver tissue as central vein deviation or absence,
      disordered arrangement of hepatic cords, narrowing of the hepatic sinusoid,
      hyperplasia of collagen fibers, formation of tuberosis, unevenness of liver cells
      with nuclear anachromasis and higher heteromorphism, and macronucleus oncocytes
      in primary HCC rats were not observed or milder after moxibustion intervention.
      CONCLUSIONS: Direct moxibustion and ginger-separated moxibustion can improve
      pathological changes of hepatic cells in rats with HCC, which may be associated
      with its actions in raising blood CD 3+ and CD 4+ T cell contents and reducing CD
      8+ T levels to improve immune function.

PMID- 29071928
TI  - [Medicinal-powder-separated Long-snake Moxibustion over the Governor Vessel with
      Different Skin Vesiculation Conditions for Treatment of Patients with Rheumatoid
      Arthritis].
AB  - OBJECTIVE: To observe the curative effect of herbal-medicine -powder-separated
      "Long-snake moxibustion" over the Governor Vessel at different vesiculation
      conditions in the treatment of rheumatoid arthritis (RA). METHODS: A total of 120
      RA patients received herbal-powder-separated long-snake moxibustion in the
      present study and randomized into Banmao (Cantharides, CANT, being able to
      promote skin vesiculation for enhancing the therapeutic effect)-0 g group, CANT
      1.5 g group and CANT-3.0 g group (n=40 in each group) according to the dosage of
      CANT used in the herbs-medicinal powder. In addition to Cantharides, the
      medicinal powder also contained Shexiang (Moschus, 1 g), Dingxiang (Flos
      Caryophylli,1 g) and Rougui (Cinnamon bark,1 g). When treated, the patient was
      asked to take a prone position, the ginger juice was evenly smeared on the
      patient's back from Dazhui (GV 14) to Yaoshu (GV 2, about 3 cm wide), then, the
      above-mentioned medicinal powder was spread on the smeared ginger juice, followed
      by putting a layer of gauze, ginger powder and ignited moxa-stick, respectively.
      The treatment was conducted once every 30 days, and twice altogether. The visual
      analog scale (VAS) was used to assess the pain seve-rity of moxibustion-induced
      skin vesiculation on the patient's back in 24 h after moxibustion. The severity
      of vesiculation was assessed according to the status of vesicles appeared at the
      local skin (0 point:no vesicles;3 points:string-of-beads-like vesicles with the
      vesicle diameter being less than 2 cm; 6 points:foliated vesicles with the
      vesicle diameter being larger than 2 cm). The patient's symptoms and dysfunction
      of hand-knee joints were scored, and serum rheumatoid factor (RF), C-reactive
      protein (CRP), immune globulin IgM and IgG contents were assayed by ELISA, and
      the erythrocyte sedimentation rate (ESR) was determined by using Westergren
      method. RESULTS: After moxibustion, of the three 40 RA patients in the CANT-0 g,
      CANT-1.5 g and CANT-3.0 g groups, 0, 10 and 12 cases were under control in their
      symptoms, 7, 16 and 19 experienced marked improvement, 17, 9 and 6 were improved,
      16, 5 and 3 failed in the treatment, with the effective rates being 60.0%(16/40),
      87.5%(35/40) and 92.5%(37/40), respectively. The curative effects of CANT-1.5 g
      and CANT-3.0 g were significantly superior to that of CANT-0 g (P<0.01). Both the
      scores for skin vesiculation status and pain severity were significantly higher
      in the CANT-3.0 g group than in the CANT-0 g (no skin vesiculation) and CANT-1.5
      g groups, and markedly higher in the CANT-1.5 g group than in the CANT-0 g group
      (P<0.01). Following the treatment, the symptom score and joint dysfunction score,
      ESR level, and serum RF, CRP, IgM and IgG contents were considerably decreased in
      the three groups in comparison with pre-treatment in the same one group (P<0.01);
      and those of the CANT-1.5 g and CANT-3.0 g groups were markedly lower than those
      of CANT-0 g group (P<0.01). In addition, CANT-3.0 g was notably superior to CANT
      1.5 g in lowering symptom and joint dysfunction scores, ESR, serum RF and CRP
      contents (P<0.05). No significant differences were found between the CANT-1.5 g
      and CANT-3.0 g groups in serum IgM and IgG levels and in the therapeutic effect
      (P>0.05). CONCLUSIONS: Long-snake moxibustion combined with CANT-induced
      vesiculation has a good curative effect in the treatment of RA, which may be
      associated with its effects in lo-wering ESR level, and serum RF, CRP, IgM and
      IgG contents. The curative effect of vesiculation moxibustion is far better than
      non-vesiculation moxibustion, but mild vesiculation moxibustion is recommended
      due to severe pain of CANT-3.0 g.

PMID- 29071929
TI  - [A Randomized Controlled Clinical Trial for Treatment of Shoulder-back Myofascial
      Pain Syndrome with Mild Moxibustion at Trigger Points].
AB  - OBJECTIVE: To compare the efficacy difference between the mild moxibustion and
      acupuncture stimulation at trigger points in the treatment of shoulder and back
      myofascial pain syndrome (MPS), so as to provide a reference for clinical
      treatment of MPS. METHODS: A total of 60 patients with shoulder and back MPS were
      equally and randomly divided into mild moxibustion group and acupuncture group.
      The myofascial trigger points in the shoulder and back regions were stimulated
      with mild moxibustion for 20-100 min every time or punctured with filiform
      needles by retaining the needles for 30 min after twirling for a while. The
      treatment was conducted once daily for 10 days. The short-form McGill pain
      questionnaire (SF-MPQ) including the pain rating index[PRI consisting of 15
      descriptors (11 sensory, 4 affective) which are rated on an intensity scale as
      0=none, 1=mild, 2=moderate and 3=severe], present pain intensity (PPI) index of
      the standard MPQ and a visual analogue scale (VAS) was used to assess the
      patient's pain severity before and after the treatment. RESULTS: Following the
      treatment, of the two 30 cases of MPS patients in the acupuncture and mild
      moxibustion groups, 1 and 7 were cured, 11 and 17 experienced marked improvement,
      14 and 5 were effective, 4 and 1 was invalid, with the effective rates being
      86.7% (26/30) and 96.7%(29/30), respectively. The cured plus markedly effective
      rate of the mild moxibustion group was significantly better than that of the
      acupuncture group(P<0.001). Self-comparison of the two groups showed that the
      scores of PRI, VAS and PPI after the treatment were apparently reduced in both
      groups compared with pre-treatment (P<0.001), but without significant differences
      between the two groups in the PRI, VAS and PPI scores after the treatment
      (P>0.05). CONCLUSIONS: Mild moxibustion stimulation of myofascial trigger point
      is effective in relieving shoulder-back MPS, being comparable to that of
      acupuncture therapy.

PMID- 29071930
TI  - [Clinical Trial of Long-snake Moxibustion Treatment for Immune Function in
      Allergic Rhinitis Disease Patients].
AB  - OBJECTIVE: To observe the curative effect of long-snake moxibustion in the
      treatment of allergic rhinitis. METHODS: A total of 66 patients with allergic
      rhinitis were randomized into moxibustion group (n=34) and control (herbal
      medicine) group (n=32) according to a computer-aided random digit table. Long
      snake moxibustion stimulation over the Governor Vessel from Dazhui (GV 14) to
      Mingmen (GV 4) was performed for 30 min, once a week for 2 consecutive months.
      Patients of the control group were treated by oral administration of "Yupingfeng"
      Granules (containing radix astragali, atrctylodis macrocephalae, etc.) one bag (5
      g) every time, 3 times a day for 2 months. Plasma IL-2, IL-6, cAMP and cGMP
      contents were detected using ELISA. RESULTS: After the treatment, of the 32 and
      34 cases in the control and moxibustion groups, 2 and 6 were cured, 12 and 16
      experienced marked improvement in their symptoms (nasal mucosal edema,
      obstruction and discharging, sneezing), 12 and 9 were improved, 6 and 3 invalid,
      with the effective rates being 81.3% and 91.2%, respectively. Results of ELISA
      showed that after the treatment, plasma IL-2, IL-6, and cGMP contents were
      significantly decreased in both the moxibustion and control groups (P<0.01),
      while plasma cAMP levels and cAMP/cGMP ratios were significantly up-regulated in
      both groups (P<0.01). The therapeutic effects of moxibustion were considerably
      superior to those of herbal medicine "Yupingfeng" in clinical effective rate and
      lowering plasma IL-2, IL-6, cGMP contents (P<0.01), and in raising plasma cGMP
      level and cAMP/cGMP ratio(P<0.01). CONCLUSIONS: Long-snake moxibustion treatment
      is effective in improving symptoms of allergic rhinitis patients, which may be
      related to its function in mobilizing the body's immune function.

PMID- 29071931
TI  - [Efficacy of Acupuncture Combined with Fire Dragon Moxibustion for Patients with
      Cervical Spondylotic Radiculopathy of Kidney-Deficiency-Cold Type].
AB  - OBJECTIVE: To compare the therapeutic effects of acupuncture combined with fire
      dragon moxibustion and simple acupuncture therapy in the treatment of patients
      with cervical spondylotic radiculopathy (CSR) of kidney-deficiency-cold type.
      METHODS: Ninety kidney-deficiency-cold type CSR outpatients were randomly divided
      into control (acupuncture, n=40) and treatment (acupuncture +moxibustion, n=50)
      groups. Acupuncture stimulation was applied to Dazhui (GV 14), Ganshu (BL 18),
      Tianzhu (BL 10) and Houxi (SI 3), Jiaji (EX-B 2), Taixi (KI 3), Shenmai (BL 62),
      Zusanli (ST 36), Shenshu (BL 23), etc once daily, 5 times a week, and two weeks
      altogether, except the weekend. In addition, for patients of the treatment group,
      herbal medicinal powder separated-fire dargon moxibustion was applied to the
      patient's back from GV14 and Fengmen (BL 12) on the top to Zhibian (BL 54) area
      at the buttock, once every 3 days, 5 times altogether. The therapeutic effect was
      evaluated according to "CSR-20-points scale" including 3 aspects as neck-shoulder
      pain, upper-limb pain-numbness, finger numbness; working and daily life ability
      and physical conditions (Spurling tests, sensory, myodynamia and tendon reflex).
      RESULTS: 1 After the treatment, CSR-20-points scores in both treatment and
      control groups were significantly increased in comparison with pre-treatment in
      each group (P<0.05), with the score being markedly higher in the treatment group
      than in the control group (P<0.05). 2 Of the 40 and 50 cases in the control and
      the treatment group, 2 and 13 were cured, 14 and 24 experienced a remarkable
      improvement, 12 and 11 were effective, and 12 and 2 failed, with the total
      effective rates being 70.0%(28/40) and 96.0%(48/50), respectively. The
      therapeutic effect of the treatment group was notably better than that of the
      control group (P<0.05). CONCLUSIONS: Acupuncture combined with fire dragon
      moxibustion is superior to simple acupuncture therapy in improving clinical
      symptoms of patients with CSR of kidney-deficiency-cold type, being a
      recommendable scheme in clinical practice.

PMID- 29071933
TI  - [Anatomical Study on Acupuncture Needle-insertion Routes of the "Nape Four
      Acupoints" in Human Corpse].
AB  - OBJECTIVE: To observe the routes of acupuncture needle-insertion of the "nape
      four acupoints"(BL 10,GB 20,GB 12, SJ 16)in the human cadavers and to explore the
      possible trigger-point location of cervical headache, so as to provide anatomic
      evidence for their clinical application. METHODS: Five human cadavers (male 3,
      female 2) were used in the present study. The needle inserting routes of the four
      acupoints Tianzhu (BL 10),Fengchi (GB 20),Wangu (GB 12) and Tianyou (SJ 16) at
      the nape were labeled with gentian violet first. The occipital tuberosity was
      taken as the original point, the horizontal projection of superior nuchal line as
      the abscissa, and the posterior median line as the ordinate, then, a two
      dimension rectangular coordinate system was established to measure the horizontal
      projection of the "nape four points" and to estimate the trigger-point location,
      followed by making an analysis on their spatial relationship, and determining the
      reasonable routes of needle-insertion of the 4 acupoints. RESULTS: For the "nape
      four points", six needling-inserting routes or spots could be taken:(1) Tianzhu
      (BL 10) I(perpendicular insertion), i.e., about 0.5 cun lateral to the posterior
      midline in parallel to BL 10; (2) Tianzhu (BL 10)II(perpendicular insertion),
      about 0.6 cun lateral to the posterior midline at the skull base level;
      (3)Tianzhu(BL10) III (perpendicular insertion),about 0.6 cun below the BL 10 and
      about 1.3 cun lateral to the posterior midline, or the right inferior of BL 10
      for oblique insertion; (4) Fengchi (GB 20) I (oblique insertion along the skull
      base toward the lower part of the nose-tip),about 2.25 cun lateral to the
      posterior midline at the depression site of the junction of the
      sternocleidomastoid and trapezius muscles on the upper portion in parallel to the
      skull base level and 2.25 cun lateral to the posterior midline; (5) Wangu(GB 12)
      I(perpendicular insertion along the bone surface), about 0.7 cun above the GB 12,
      i.e., the inferior of the junction of the mastoid posterior root and the skull
      base; (6)Tianyou (SJ 16)I, about 0.7 cun below the SJ 16, i.e., the posterior
      margin of the sternocleidomastoid muscle, being the same to SJ 16 in the
      operation. CONCLUSIONS: According to anatomical analysis, it is recommended to
      insert the acupuncture needles into the nape four acupoints along the Tianzhu (BL
      10) I, II, III, Fengchi(GB 20)I, Wangu (GB 12) I and Tianyou(SJ 16)I routes
      mentioned above for achieving a better therapeutic effect. Cervical headache may
      have a close relation with the trigger-points at the occipital nape.

PMID- 29071932
TI  - [Randomized Clinical Trial for Treatment of Patients with Acute Ischemic Cerebral
      Stroke by Acupoint Injection of Cobalamin or Gangliosides].
AB  - OBJECTIVE: To observe the clinical therapeutic effect of acupoint injection of
      medicine in the treatment of patients with acute cerebral ischemia stroke (ACIS).
      METHODS: Ninety ACIS patients were randomized into control, Cobalamin and
      Gangliosides groups (n=30 in each group). Patients of the control group were
      treated by routine medication (i.e., drugs for improving microcirculation, anti
      platelet aggregation, cerebral dehydration, neuronutrition, intracranial pressure
      reduction and blood lipid-lowering, etc.) and motor function rehabilitation
      training, once daily, six times a week for two weeks; and those of the Cobalamin
      and Gangliosides groups were treated by injection of Cobalamin (1 mL) or
      Gangliosides (1 mL) into Baihui (GV 20) and Zusanli (ST 36), respectively and
      rehabilitation training (being the same to the control group). The patients'
      motor ability and physical status were assessed according to clinical neurologic
      deficit score (CNDS) and activity of daily living scale (ADLS). RESULTS: After
      the treatment, of the three 30 cases in the control, Cobalamin and Gangliosides
      groups, 0, 4 and 2 were cured, 9, 15 and 14 experienced marked improvement in
      their symptoms, 12, 8 and 10 were improved, 9, 3 and 4 invalid, with the
      effective rates being 70.0%(21/30), 90.0%(27/30) and 86.7%(26/30), respectively.
      In comparison with pre-treatment, the CNDS of the three groups were all
      significantly decreased and the ADLS notably increased (P<0.05). The effects of
      both Cobalamin and Gangliosides were remarkably better than those of the control
      in lowering CNDS and raising ADLS (P<0.05), and the score of ADLS in the
      Cobalamin group was markedly higher than that in the Gangliosides group (P<0.05).
      CONCLUSIONS: Acupoint injection of both Cobalamin and Gangliosides can
      effectively improve acute ischemic stroke patients' neurological function and
      daily life living ability.

PMID- 29071934
TI  - [Dynamic Changes of Fast Spin-echo T 2 Weighted Images Displayed Topical
      Reactions to Micro-invasive Catgut-embedment of Zusanli (ST 36) in Healthy
      Volunteer Subjects].
AB  - OBJECTIVE: To observe the duration of local reactions after subcutaneous micro
      invasive catgut-embedding stimulation in Zusanli(ST 36) region in normal human
      body by using magnetic resonance (MR) T 2-mapping, so as to find a reasonable
      interval between every two catgut-embedding performance. METHODS: A total of 8
      normal volunteers (3 women, and 5 men) were enrolled in the present study. Before
      and 8 h, and 3, 7, 14, 21, 28 and 35 days after the subcutaneous micro-invasive
      embedment of catgut (Gauge 2.0, 2 cm long) in the left Zusanli (ST 36) area, the
      local T 2-weighted images (T 2 WI) and fat-suppression T 2-weighted images (FS T
      2 WI) were detected and recorded by using MR scan (GE Optima MR 360 1.5 T) and
      analyzed using FuncTool software. RESULTS: Compared with pre-catgut-embedment,
      the local signal strength of T 2 FS WI and T 2 relaxation time began to rise on
      the 8th hour after catgut-embedment, peaked on the 3rd day, began to descend on
      the 7th day, but being still higher than pre-embedment, and turned to the normal
      level on the 21st day to the 35th day. Results of statistical analysis displayed
      that compared with pre-catgut-embedment, T 2 relaxation time levels were
      significantly higher on the 8th h, day 3, 7 and 14 after the embedment (P<0.01),
      and were comparable to that of pre-embedment on day 21, 28 and 35 (P>0.05).
      CONCLUSIONS: Catgut-embedment of Zusanli (ST 36) induces an apparent change of
      MRI signals from the 8th h to the 14th day in normal volunteer subjects,
      suggesting that an interval of 21 days may be reasonable for the micro-invasion
      catgut-embedment in clinical practice.

PMID- 29071935
TI  - [Variation of Locations of Baliao Acupoints in 290 Volunteer Subjects Analyzed by
      Using Computed Tomography-aided Three-dimensional Reconstruction Technique].
AB  - OBJECTIVE: To observe the variation of sacral vertebrates and foramen involving
      the bilateral Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 33) and Xialiao
      (BL 34, Baliao acupoints), so as to provide an anatomic basis of acupoint
      needling in clinical practice. METHODS: A total of 290 patients[161 men and 129
      women, mean age and standard devia-tion, (63.6+/-13.3)years old and (59.5+/-13.3)
      years old, respectively] with intact pelvic structure were recruited in the
      present study. Computed tomography (CT) scans of intact pelves were taken using a
      SOMATOM Definition AS 128 and the acquired signals were imported into Siemens
      Syngo Inspace platform for 3 D reconstruction, followed by identification,
      classification and analysis of the variation of sacral foramen (Baliao acupoint).
      RESULTS: The total variation rate of posterior sacral foramen (Baliao acupoint)
      was 20.34%(59/290). The detected three types of variation were sacral vertebrae
      number variation (4 sacral vertebraes, 6 sacral vertebraes), fusion variant
      (lumbosacral fusion, sacrococcygeal fusion, lumbosacral & sacrococcygeal fusion,
      and lumbosacral fusion & S 4 variation) and mixed type. CONCLUSIONS: Variations
      of sacral vertebrae including the number and fusion exist in the human body,
      suggesting an increase of the difficulty of acupoint needling. Since posterior
      iliac spine does not change generally, it is recommended to be used as a
      reference point for locating the Baliao acupoint.

PMID- 29071936
TI  - [Clinical Advantages and Acupoint Selection of Treatment of Chronic Functional
      Constipation with Acupuncture Therapy].
AB  - Abundant clinical practice has showed that acupuncture therapy has some distinct
      advantages in the treatment of chronic functional constipation (CFC), such as
      faster positive effect, shorter course of treatment, long-term post-effect, etc.
      In the present paper, the authors reviewed progresses of researches in clinical
      treatment of CFC with acupuncture therapy in recent years. Results of clinical
      trials indicated that among the 3 types (slow transit, outlet obstruction and
      mixed type) of constipation, acupuncture therapy showed a better effect for slow
      transit constipation by improving severity, increasing defecation frequency,
      reducing abdominal distension, easing patients' psychological discomfort and
      raising daily life activity, probably by ameliorating colonic motility, enteric
      nervous system function and neurotransmitter secretion (vasoactive intestinal
      peptide, acetylcholine, substance P, nitrix oxide,etc.). Most of the chosen
      acupoints (ST 25, SP 15, SP 14, CV 6, BL 25, BL 23, etc.) are located in the
      projection region of colon. For outlet obstruction defecation, the effect of
      acupuncture is relatively better for chalasia type, in spite of generally being
      poorer in the efficacy. Majority of the selected acupoints (GV 1, BL 32, BL 33,
      BL 30, etc.)are located near the pelvic floor region. In addition, the clinical
      therapeutic effects of acupuncture need being confirmed by more large sample,
      multiple centers randomized controlled trials.

PMID- 29071937
TI  - [Involvement of Central Neuroglia Cells in Analgesic Effect of Electroacupuncture
      Therapy for Neuropathic Pain].
AB  - Neuropathic pain is one of the common chronic syndromes in clinical practice. It
      has been demonstrated that the chronic neuropathic pain and glial cells in the
      central nervous system are closely related to each other. When inducing analgesic
      effect in neuropathic pain, EA suppressed OX-42 labeled activation of
      microgliacytes in dorsal horns of the spinal cord, down-regulated release of
      nitric oxide (NO), expression of P 2 X4 receptor, intracellular mitogen-activated
      protein kinase (MAPK), extracellular regulated protein kinases (ERK),
      proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha, interferon (IF)-gamma and
      up-regulated neurotrophin-3 expression in neuropathic pain rats. In regard to
      spinal astrocytes, acupuncture suppressed peripheral nerve injury induced
      activation of GFAP-labeled astrocytes, down-regulated the expression levels of
      macrophage inflammatory proteins (MIP)-1, MIP-1 beta, MIP-3 alpha, TNF-alpha mRNA
      and IL-1 beta mRNA, etc. in the dorsal horns of the spinal cord. Up to now, the
      underlying me-chanisms of acupuncture in regulating activities of glia cells, and
      interaction between neurons and glia cells, and the related pathways in the
      peripheral and central systems remain unclear. The effects of some related
      protein and gene expressions involving in acupuncture analgesia need being
      confirmed by adopting different approaches.

PMID- 29071938
TI  - [Evolution of Classification Methods and Nomenclature of Clinical Disorders
      Treated by Acupuncture and Moxibustion in the 20th Century].
AB  - Through systematic review of the literature on the treatment of different
      clinical conditions or illnesses with acupuncture and moxibustion therapies in
      the 20th century, the authors of the present paper analyzed the evolution process
      of classification of related clinical disorders. It was found that the
      classification and nomenclature of clinical disorders or illnesses are defined in
      terms of traditional Chinese medicine or western medicine, which undergoes an
      evolutionary process from western medicine to Chinese medicine and back to
      western medicine. This evolution process is due to the intrinsic requirement' of
      clinical practice such as thinking ways of diagnosis and treatment or to be
      influenced by extrinsic factors including introduction of western medicine at the
      Republic period, policies of"advanced studies of traditional Chinese physcians"
      and "western medicine doctors" lear-ning from traditional Chinese medicine, and
      the leading role of western medicine,etc. The former issue about the diagnosis
      and treatment of clinical problems needs being researched further.

PMID- 29071939
TI  - [Research on Acupuncture Anesthesia-analgesia].
AB  - In the present paper, the author retrospects the historical developmental stages
      of acupuncture anesthesia-analgesia from 1) preliminary exploration:the creative
      application of acupuncture therapy to surgery with lower dosage or without
      anesthetics began in Shanghai and Xi'an in 1958; 2) clinical popularization:the
      acupuncture anesthesia-analgesia became popularized from 1965, peaked in 1970s'
      and declined from 1980s'; 3) mechanism study:from 1970 to 2000, a large quantity
      of research papers were published to confirm the validity of acupuncture
      analgesia (AA), and in 1997, NIH Consensus Conference for acupuncture was held,
      promoting the related research in the world; 4) focused research:from 2007 to
      now, the acupuncture anesthesia-analgesia was listed as one of the key research
      program in China; 5) theoretical summary:in view of the uncertainty of the
      scientific basis of the meridian system of traditional Chinese medicine, the
      nerve fibers distributed under the acupoint are now considered to be the
      indispensable components for AA, and the knowledge of modern neuroscience is
      competent to explain the underlying mechanism of AA; 6) returning to reality:AA
      has been accepted by the international scientific community, and the "acupuncture
      assisted anesthesia", or "compound acupuncture and anesthetics anesthesia" has
      been used as the first choice for some types of surgical operation. The research
      on acupuncture anesthesia-analgesia greatly facilitates clinical application of
      acupuncture therapy in the world, and also promotes the development of
      acupuncture therapy itself and neuroscience. However, the transformation between
      theory and practice and their mutual interaction are endless endeavor. Thus, a
      careful review of the half-century-long practice of acupuncture anesthesia
      analgesia is painstakingly necessary in order to clarifying the mechanisms, to
      raise the efficacy of clinical practice and to correct the possible errors
      referred to this concept.

PMID- 29071940
TI  - [Effect of Electroacupuncture Serum on Proliferation of Cultured Multifidus
      Muscle Satellite Cells and Expression of Pax-7, MyoD and p-Akt].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) serum on
      proliferation of multifidus muscle sa-tellite cells (SCs) and expression of
      paired box transcription factor Pax-7, MyoD and protein kinase B (PKB or Akt)
      proteins of SCs, so as to explore its underlying mechanism in promoting repair of
      multifidus muscles. METHODS: Thirty-two SD rats were randomly assigned to
      control, model, EA-Weizhong (BL 40) and EA-Shenshu (BL 23) groups. The multifidus
      muscle injury (MFMI) model was established by injection of 0.5% bupivacaine
      hydrochloride (400 MUL) into the bilateral L4-L5 paravertebral muscles (4 points,
      100 MUL for each point). EA stimulation was separately applied to bilateral BL 40
      and BL 23 for 20 min, once daily, 4 days altogether. Blood samples of the
      abdominal artery of rats in the above mentioned 4 groups were separately
      collected for extracting serum, followed by deactivation and filtration, and then
      were respectively applied to the Dulbecco's Modified Eagle Media (DMEM) culturing
      each multifidus muscle SCs of the normal serum, model serum, EA-BL 40 serum and
      EA-BL 40 serum+LY 294002 (an inhibitor of phosphotidylinsitol-3-kinase, PI 3 K),
      EA-BL 23 serum and EA-BL 23 serum+LY 294002 groups for ana-lyzing the impact of
      EA serum on the proliferation state of SCs by Cell Counting Kit-8 (CCK-8) and 5
      Ethynyl-2'-deoxyuridine (EdU) methods, respectively. The expression of Pax-7,
      MyoD and phosphorylated (p)-Akt proteins of the cultured SCs was detected for
      characterization of SCs by Western blot. RESULTS: Compared with the normal serum
      group, the proliferation levels (detected by both CCK-8- and EdU) and the
      expression levels of MyoD and p-Akt proteins of SCs in the model serum group were
      significantly increased (P<0.05, P<0.01), while in comparison with the model
      serum group, the proliferation and expression levels of MyoD and p-Akt proteins
      of SCs were further significantly increased in both EA-BL 23 and EA-BL 40 serum
      groups (P<0.01, P<0.05), but not in the EA-BL 40 serum+LY 294002 and EA-BL 23
      serum+LY 294002 groups (P>0.05), suggesting an involvement of PI 3 K in the
      proliferation of SCs. No marked differences were found in the proliferation
      levels between the EA-BL 23 and EA-BL 40 serum groups and in the expression
      levels of Pax-7 proteins among the 6 serum groups (P>0.05). CONCLUSIONS: Both EA
      BL 40 and EA-BL 23 serum can promote proliferation of multifidus muscle SCs,
      which may contribute to the effect of EA intervention in promoting repair of the
      injured muscle, partially by way of Akt/PI 3 K signaling.

PMID- 29071941
TI  - [Penetrative Needling from "Baihui" (GV 20) to "Qubin" (GB 7) Antagonizes
      Inflammatory Injury in Rats with Cerebral Hemorrhage].
AB  - OBJECTIVE: To observe the effect of penetrative needling of "Baihui" (GV 20) to
      "Qubin" (GB 7) on neurologic functions and expression of tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-6 and toll-like receptor 4 (TLR-4, involving in
      inflammatory reactions) in the tissue around the local cerebral hematoma in rats
      with intracerebral hemorrhage (ICH), so as to provide evidence for clinical
      treatment of ICH. METHODS: Fifty-four male Wistar rats were randomly divided into
      sham control, mo-del and acupuncture groups, and then further divided into three
      time-point subgroups(1,3,7 days after modeling, n=6/subgroup). The ICH model was
      established by injection of the rat's autoblood (50 MUL) into the putaman region
      (P:0.2 mm, R:3.5 mm) in a stereotaxic apparatus and confirmed by Berderson's
      neurologic examination grading system (0-3 points). The neurologic function was
      assessed by using Longa's scoring (5-points) and footfault asymmetry
      testing[footfault index=(contra faults-ipsi faults)/total steps in 2 min]. For
      penetrative needling, an acupuncture needle was inserted into GV 20 and
      controlled to advance to GB 7 on the affected side and retained for 30 min, once
      daily. The expression of TNF-alpha, IL-6 and TLR-4 in the cerebral tissue around
      the putaman was detected by immunohistochemistry. RESULTS: After penetrative
      needling stimulation, the increased Longa's score and footfault asymmetry score
      in ICH rats were significantly decreased on day 1, 3 and 7 after modeling
      (P<0.01), suggesting an improvement of neurologic function after the treatment.
      Immunohistochemical staining outcomes of the cerebral tissue surrounding the
      autoblood injection site showed that the expression levels of TNF-alpha, IL-6 and
      TLR-4 proteins on day 1, 3 and 7 were considerably higher in the model group than
      in the control group (P<0.01), and markedly lower in the acupuncture group than
      in the model group (P<0.01), suggesting a suppression of the proinflammatory
      factors and TLR-4 levels around the locus of the brain after needling
      intervention. A positive correlation existed between the expression levels of TLR
      4 and IL-6/TNF-alpha. CONCLUSIONS: Penetrative needling stimulation of GV 20 to
      GB 7 can reduce the levels of proinflammatory factors TNF-alpha and IL-6, and TLR
      4 in the ICH tissues in rats with cerebral hemorrhage, which may contribute to
      its effect in improving neurological function.

PMID- 29071942
TI  - [Effect of Scalp-acupuncture Stimulation on Neurological Function and Expression
      of ASIC 1 a and ASIC 2 b of Hippocampal CA 1 Region in Cerebral Ischemia Rats].
AB  - OBJECTIVE: To observe the influence of scalp-acupuncture on the expression of
      acid-sensing ion channels (ASICs) 1 a and 2 b of hippocampal CA 1 region in
      cerebral ischemia (CI) rats, so as to investigate its mechanism underlying
      improvement of ischemic stroke. METHODS: Thirty-two male SD rats were randomly
      allocated to normal control, model, scalp-acupuncture and Amiloride group (n=8 in
      each group). The model of focal CI was established by middle cerebral artery
      occlusion (MCAO). Scalp acupuncture stimulation was applied to bilateral
      Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7), once daily for 7 days.
      Rats of the Amiloride group were fed with Amiloride solution, twice a day for 7
      days, and those of the normal control and model groups were grabbled and fixed in
      the same way with the acupuncture and Amiloride groups. The neurological deficit
      score was given according to Longa's method. The expression of hippocampal ASIC 1
      a and ASIC 2 b was detected by immunohistochemistry, and the Ca2+ concentration
      in the hippocampal tissue assayed using flowing cytometry. RESULTS: After the
      intervention, the neurological deficit score of both the scalp-acupuncture and
      Amiloride groups were significantly decreased in comparison with pre-treatment
      (P<0.01), and the effect of scalp-acupuncture was markedly superior to that of
      Amiloride in reducing neurological deficit score (P<0.05). The expression of ASIC
      1 a and ASIC 2 b in the hippocampal CA 1 region and hip-pocampal Ca2+
      concentration were significantly up-regulated in the model group compared with
      the normal control group (P<0.01), and obviously down-regulated in both scalp
      acupuncture and Amiloride groups (P<0.01, P<0.05),without significant differences
      between the two treatment groups in the ASIC 1 a and ASIC 2 b expression and Ca2+
      concentration (P>0.05). CONCLUSIONS: Scalp-acupuncture stimulation can improve
      neurological function in CI rats, which may be related to its effects in
      suppressing the increased expression of hippocampal ASIC 1 a and ASIC 2 b
      proteins and in reducing calcium overload in hip-pocampal neurocytes.

PMID- 29071943
TI  - [Effects of Electroacupuncture on Expression of Myocardial Chloride Channel-2 and
      CLCA Proteins in Mice with Acute Myocardial Ischemia].
AB  - OBJECTIVE: To observe the influence of electroacupuncture stimulation (EA) of
      "Neiguan" (PC 6)/"Lieque" (LU 7) on ST segment of electrocardiogram (ECG) and the
      expression of myocardiac chloride channel (CLC)-2 and calcium (Ca2+)-activated
      chloride channel accessory (CLCA) proteins in acute myocardial ischemia (AMI)
      mice, so as to explore its mechanisms underlying improvement of AMI. METHODS:
      Thirty ASIC 3-/- knock out mice were randomly divided into control, AMI model, EA
      Neiguan (PC 6), EA-Lieque (LU 7) and EA-non-acupoint groups. The AMI model was
      induced by multiple subcuta-neous injection of isoprenaline (ISO, 0.5 g/L, 20
      mg/kg). EA was applied to bilateral PC 6, LU 7, or non-acupoint[the mid-point
      between "Tianshu" (ST 25) and "Shenque" (CV 8)] for 20 min, once daily for 7
      days. The ST segment of ECG of the standard IIlimb-lead was recorded using a
      PowerLab data acquisition device, the change of myocardial histology observed by
      using microscope after HE staining, the activity of serum superoxide dismutase
      (SOD) detected using Colorimetric method, and the expression of CLC-2 and CLCA
      proteins of the left ventricle myocardium detected by Western blot. RESULTS:
      Outcomes of HE staining showed that the ischemic injury (sarcoplasm swelling and
      necrosis, etc.) of the left ventrical myocardial tissue after mo-deling was
      relatively milder in the EA-PC 6 group, not in the EA-non-acupoint group. The SOD
      activity was significantly lower in the model group than in the control group
      (P<0.01), and obviously increased in the EA-PC 6 group(P<0.01), but not in the EA
      non-acupoint group (P>0.05). The expression levels of myocardial CLC-2 and CLCA
      proteins were significantly up-regulated in the model group compared with the
      control group (P<0.01) and markedly down-regulated in the EA-PC 6 group (not in
      the EA-non-acupoint group) in comparison with the model group(P<0.01), suggesting
      a specificity of effects of EA-PC 6 in improving myocardial injury and down
      regulating CLC-2 and CLCA protein expression. CONCLUSIONS: EA of "Neiguan" (PC 6)
      can effectively suppress the increase of expression of CLC-2 and CLCA proteins in
      the left ventricle myocardium, which may contribute to its effect in relieving
      myocardial injury in mice.

PMID- 29071944
TI  - [Effect of Moxibustion Stimulation of "Feishu" (BL 13) and "Xinshu" (BL 15) on
      Expression of Myocardial MyD 88 Protein and Caspase 3 mRNA in Chronic Heart
      Failure Rats].
AB  - OBJECTIVE: To observe the effect of moxibustion stimulation of "Feishu" (BL 13)
      and "Xinshu" (BL 15) on pathological changes of myocardium and the expression of
      myocardial myeloid differentiation factor 88 (MyD 88) protein and Caspase 3 mRNA
      in chronic heart failure (CHF) rats, so as to explore its mechanism underlying
      improvement of CHF. METHODS: SD male rats were randomly divided into normal
      (n=9), model (n=8), moxibustion (n=8), medication (n=8) and moxibustion +
      medication (n=8) groups. In addition, the other 6 rats (3/normal and 3/model
      groups) were used for measuring cardiac ventricle weight and H.E. stain. The CHF
      model was made by intraperitoneal injection of Adriamycin (ADR, from 1 to 4
      mg/kg, once every other day for 15 days). Mild moxibustion was applied to
      bilateral BL13 and BL15 for 15 min, once daily for 3 weeks. Rats of the
      medication group were treated by Captopril (gavage) for 3 weeks. The expression
      of myocardial Caspase 3 mRNA and MyD 88 protein of the left ventricle was
      determined by quantitative real time-PCR and Western blot, respectively. RESULTS:
      In comparison with the normal group, the myocardial damage (cell swelling,
      cytoplasma vaculation, and disordered arrangement, rupture and lysis of some
      cardiac muscle fibers), and the expression levels of myocardial MyD 88 protein
      and Caspase 3 mRNA were obviously increased in the model group(P<0.01). After the
      interventions, the myocardial damage was relatively milder, and the expression of
      myocardial MyD 88 protein and Caspase 3 mRNA were significantly down-regulated in
      the moxibustion, me-dication and moxibustion+medication groups in comparison with
      the model group(P<0.05). No significant differences were found among the 3
      treatment groups in the expression levels of MyD 88 protein and Caspase 3
      mRNA(P>0.05). CONCLUSIONS: Moxibustion intervention can suppress CHF induced up
      regulation of expression of myocardial MyD 88 protein and Caspase 3 mRNA in rats,
      which may contribute to its effect in relieving myocardial injury.

PMID- 29071945
TI  - [Electroacupuncture Combined with Clomiphene Promotes Pregnancy and Blastocyst
      Implantation Possibly by Up-regulating Expression of Insulin Receptor and Insulin
      Receptor Substrate 1 Proteins in Endometrium in Rats with PCOS].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention combined
      with clomiphene critate (CC) on the blastocyst implantation and pregnancy rate
      and expression of insulin receptor (INSR) and insulin receptor substrate 1 (IRS
      1) proteins in the endometrium in rats with polycystic ovary syndrome (PCOS), so
      as to reveal its mechanisms underlying improvement of PCOS. METHODS: One hundred
      and twenty-five female SD rats were randomly divided into normal control, PCOS
      model, medication (CC), EA and EA+CC groups (n=25 in each group, 15 for checking
      blastocyst implantation, and 10 for Western blot). The PCOS model was established
      by subcutaneous injection of Dehydroepiandrosterone (DHEA) and fed with high-fat
      diet. Rats of the normal control group were treated by subcutaneous injection of
      sesame oil and fed with the normal forage. EA stimulation was applied to
      "Zhongwan" (CV 12), "Guanyuan" (CV 4) and bilateral "Tianshu" (ST 25) for 30 min,
      3 times a week, 5 weeks altogether. Rats of the CC and EA+CC groups were fed with
      CC (100 mg.kg-1.d-1) for 2 days after regular restriction (30 min, 3 times a
      week, 5 weeks altogether). The pregnancy was determined by vaginal smear tests
      and the number of blastocyst implantation determined by examination of the uterus
      after execution. The expression of INSR and IRS 1 proteins in the endometrium was
      detected by Western blot. RESULTS: The pregnancy rate and the number of
      blastocyst implantation were significantly lower in the model group than in the
      normal control group (P<0.05), and remarkably increased after EA and EA+CC
      interventions (P<0.05). The effects of EA+CC were obviously superior to those of
      simple EA and simple medication in raising the pregnancy rate and the number of
      blastocyst implantation (P<0.05). No significant differences were found between
      the EA and CC groups in the pregnancy rate and the number of blastocyst
      implantation (P>0.05). The relative expression levels of both INSR and IRS 1
      proteins were markedly lower in the model group than in the normal control group
      (P<0.05), and significantly higher in both EA and EA+CC groups than in the model
      group (P<0.05). No significant differences were found between the model and the
      CC groups and between the EA and EA+CC groups in the expression levels of INSR
      and IRS 1 proteins (P>0.05). CONCLUSIONS: EA intervention can improve pregnancy
      rate and the number of blastocyst implantation in PCOS rats, which may be related
      to its effects in up-regulating the expression of INSR and IRS 1 proteins in the
      endometrium.

PMID- 29071946
TI  - [Effects of Electroacupuncture on Joint Function in Rheumatoid Arthritis Patients
      of Liver- and Kidney-Yin Deficiency Type].
AB  - OBJECTIVE: To compare the effects between electroacupuncture (EA) plus western
      medicine and simple western medicine in improving clinical symptoms and local
      joint function of rheumatoid arthritis (RA) patients with yin deficiency of Liver
      and Kidney. METHODS: A total of 68 RA patients of yin deficiency of Liver and
      Kidney were equally randomized into EA+medication group and medication group
      (n=34 in each group). Both groups were given once-a-week methotrexate (7.5
      mg/time) and once-a-day leflunomide (10 mg/time), while EA+medication group was
      additionally treated by EA at bilateral Ganshu (BL 18), Shenshu (BL 23),
      Xuanzhong (GB 39), Zusanli (ST 36), Taichong (LR 3), Hegu (LI 4) 3 times/week.
      The treatment lasted for 12 weeks. The visual analogue scale (VAS, for assessing
      rest pain), swollen joint count (SJC), tender joint count (TJC), patient's global
      assessment (PGA), physician's global assessment (PhGA), traditional Chinese
      medicine (TCM) symptom scoring, 28 joints activity index (disease activity score,
      DAS 28), American College of Rheumatology 20 (ACR 20, i.e. 20% of clinical
      improving rate), and health assessment questionnaire (HAQ) were assessed and
      erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) levels were
      examined for comparison. RESULTS: Statistical differences were observed in before
      after-treatment comparisons in both groups in reducing rest pain, SJC, TJC, serum
      CRP content, PGA and PhGA, HAQ scoring and DAS 28 (P<0.05, P<0.01). The ESR in
      the medication group and TCM symptom scoring of the EA+medication group were also
      significantly decreased after the treatment (P<0.05).The effects of the
      EA+medication group were superior to those of the medication group in reducing
      rest pain, SJC, TJC, TCM symptom and HAQ score, and the total effetive rate
      (P<0.05,90.9% vs 66.67%). Adverse reactions as pharyngeal obstruction sensation,
      anorexia, abdominal distension, etc. can be reduced by EA therapy coordinated
      with western medicine. CONCLUSIONS: EA is effective in relieving symptom and
      joint function in RA patients with yin deficiency of Liver and Kidney.

PMID- 29071947
TI  - [A Randomized Controlled Clinical Trial of Treatment of Lumbar Disc Herniation
      induced Sciatica by Acupuncture Stimulation of Sciatic Nerve Trunk].
AB  - OBJECTIVE: To observe the efficacy of acupuncture stimulation of the sciatic
      nerve trunk in the treatment of patients suffering from sciatica induced by
      lumbar disc herniation (LDH). METHODS: A total of 60 LDH sciatica patients met
      the inclusion criteria were randomly divided into treatment group and control
      group, with 30 cases in each. Patients of the treatment group were treated by
      directly needling the sciatic nerve and routine acupuncture of Ashi-points,
      Lumbar Jiaji (EX-B 2), Dachangshu (BL 28), etc., and those of the control group
      treated by simple routine acupuncture. The treatment was conducted once a day, 5
      times a week, 4 weeks altogether. The clinical effect was evaluated according to
      the "Standards for Diagnosis and Therapeutic Effect Evaluation of Syndromes of
      Chinese Medicine" and the pain intensity was assessed by using simplified Short
      Form McGill Pain Questionnaire (SF-MPQ) containing pain rating index (PRI),
      visual analogue scale (VAS) and present pain intensity (PPI). RESULTS: After the
      treatment, of the two 30 cases of LDH sciatica patients in the control and
      treatment groups, 11 and 18 were cured, 7 and 7 experienced marked improvement,
      10 and 4 were effective, 2 and 1 was invalid, with the effective rate being 93.3%
      and 96.7%, respectively. The cured+markedly effective rate of the treatment group
      was significantly higher than that of the control group (P<0.05, 83.3% vs 60.0%).
      Compared with pre-treatment, the scores of PRI, VAS and PPI were evidently
      lowered in both groups (P<0.01), and the effect of the treatment group was
      notably better than that of the control group (P<0.01). CONCLUSIONS: Acupuncture
      stimulation of the sciatic nerve trunk is effective in relieving sciatica in LDH
      patients, and is superior to simple routine acupuncture in the clinical efficacy.

PMID- 29071948
TI  - [Evaluate the Efficacy of Electroacupuncture Therapy on Abdominal Fat in Obese
      Women by Using Magnetic Resonance Imaging].
AB  - OBJECTIVE: To evaluate the efficacy of electroacupuncture (EA) therapy on
      abdominal fat in obese women by using magnetic resonance imaging(MRI). METHODS:
      Thirty abdominal obesity women patients were randomly divided into control group
      (n=15) and EA group (n=15). The obesity patients of the control group did not
      receive any treatment for weight reduction, and those of the EA group were
      treated by EA stimulation of bilateral Neiting (ST 44), Fenglong (ST 40), Zusanli
      (ST 36), Huaroumen (ST 24), Tianshu (ST 25), Wailing (ST 26), Shuidao (ST 28),
      Fujie (SP 14), Daheng (SP 13), etc. for 25 min, once every other day, 3 times per
      week for 3 months. The patient's body weight, height, waist circumference (WC)
      were mea-sured with different devices, and the body mass index (BMI) was
      calculated, and the subcutaneous adipose tissue thickness at the inferior edges
      of L4, L5 and S3 and the superior edge of the pubic symphysis and the total
      abdominal fat volume between the L4 and S3 levels were detected using MRI systems
      before and after the treatment. RESULTS: The effects of the EA group were
      significantly superior to those of the control group in lowering difference
      values (between pre- and post-treatment) of BMI, WC and subcutaneous adipose
      tissue thickness at the levels of the inferior edges of L4, L5, S3 and the
      superior edge of the pubic symphysis(all P<0.01)and in reducing total abdominal
      fat volume between L4 and S3 (all P<0.01). After the treatment, the subcutaneous
      adipose tissue thickness at the superior edge of the pubic symphysis (P<0.01) and
      the total abdominal fat volume between L4 and S3 (P<0.05) were significantly
      decreased in the EA group compared to pre-treatment. There were no significant
      differences between post- and pre-treatment in BMI, WC, subcutaneous adipose
      tissue thickness at the levels of the L4, L5 and S3 in both EA and control groups
      and in the subcutaneous adipose tissue thickness at the level of the superior
      edge of the pubic symphysis and the total abdominal fat volume between L4 and S3
      in the control group (P>0.05). CONCLUSIONS: EA intervention can effectively
      reduce abdominal fat in obese women based on the evaluation of MRI.

PMID- 29071949
TI  - [A Randomized Controlled Clinical Trial for Electroacupuncture Treatment of Post
      surgical Gastrointestinal Dysfunction in Patients Undergoing Laparotomy].
AB  - OBJECTIVE: To evaluate the clinical efficacy of electroacupuncture (EA)
      stimulation of Zusanli (ST 36) and Neiguan (PC 6) in the treatment of persistent
      postoperative gastrointestinal dysfunction in patients undergoing laparotomy.
      METHODS: A total of 60 laparotomy patients were enlisted in the present study and
      were randomly divided into conventional treatment group (control) and EA group
      (n=30 in each group). Patients of the EA group were treated by conventional
      treatment and EA stimulation (2 Hz, 1-10 mA) of bilateral ST 36 and PC 6 for 30
      min, once daily for 5 days, and patients of the control group treated by
      conventional treatment (pre- and post-surgical fasting, measures for
      gastrointestinal decompression, electrolyte stabilization, parenteral nutrition
      support, and anti-infection in necessity, etc). The first postoperative flatus
      and defecation time, postoperative hospital stays,abdominal bloating grading (0-4
      points, i.e. Likert scale), and adverse events were recorded and evaluated.
      RESULTS: After the treatment, the first postoperative flatus and defecation time,
      and hospital stay time and abdominal bloating scores from the 2nd to the 5th day
      post-surgery in the EA group were significantly lower than those of the control
      group (P<0.05). The abdominal bloating scores of the two groups were gradually
      and obviously decreased from the 2nd day on in comparison with pre-treatment
      (P<0.05). Of the two 30 cases in the control and EA groups, 5 and 14 were cured
      in their clinical symptoms, 15 and 13 experienced marked improvement, 7 and 3
      were effective, 2 and 0 invalid, with the effective rates being 66.7% and 90.0%,
      respectively. CONCLUSIONS: EA is effective in improving persistent postoperative
      gastrointestinal dysfunction in cancer patients undergoing laparotomy.

PMID- 29071950
TI  - [Observation on Effectiveness of Acupuncture Treatment of Children with Spastic
      Cerebral Palsy by Stimulating Acupoints Selected According to the Day to Match
      the Heavenly Stems and Earthly Branches].
AB  - OBJECTIVE: To evaluate the clinical effectiveness of acupuncture in the treatment
      of spastic cerebral palsy (CP) children by stimulating acupoints selected
      according to the day to match the heavenly stems and earthly branches (Ziwu Liu
      zhu Najia Zhenfa). METHODS: A total of 130 CP patients were randomized into a
      control group and a treatment group (n=65 in each). Both groups were given with
      routine rehabilitation therapy, while the treatment group additionally received 3
      months' acupuncture intervention. All patients were assessed before and after
      treatment with gross motor function measure (GMFM-88), mo-dified Ashworth scale
      (MAS) and activities of daily living (ADL) in cerebral palsy. RESULTS: After the
      treatment, the control group scored (25.12+/-2.74) points in GMFM-88, (1.53+/
      0.71) points in MAS, (19.25+/-5.08) points in ADL, while the treatment group were
      respectively (31.87+/-2.58) points in GMFM-88, (1.07+/-0.74) points in MAS,
      (25.67+/-6.15) points in ADL. Both groups experienced significant improvement in
      increasing GMFM-88 and ADL scores, and reducing MAS score compared to those
      before treatment (P<0.05, P<0.01), and the effects of the treatment group were
      evidently superior to those of the control group in increasing GMFM-88 and ADL
      scores, and reducing MAS score (P<0.05). CONCLUSIONS: The "Ziwu Liuzhu Najia
      Zhenfa" acupuncture achieved greater improvement in gross motor function and
      reduction in muscular tone and enhancement of capacity of daily living activity.

PMID- 29071951
TI  - [A Newly-made Rat Holder for Convenient Acupuncture Needle Insertion].
AB  - In the present article, the authors introduce a newly-made rat holder device for
      easily inserting acupuncture needles into the acupoints at any parts of the body.
      This device is easy in operation and higher in applicability, being worthy of
      popularization for researchers engaging in experimental studies.

PMID- 29071952
TI  - [Development of Researches on Cytokine Mechanisms in Analgesia and Anti
      inflammation in Acupuncture Therapy for Rheumatoid Arthritis].
AB  - Cytokines are closely related to the occurrence and development of rheumatoid
      arthritis(RA). Acupuncture exerts anti-inflammatory and analgesic effects via
      elevating anti-inflammatory cytokine level and reducing pro-inflammatory cytokine
      level and regulating Th 1/Th 2 balance, which reflects the dual directional
      regulatory effect of acupuncture. However, problems exist in the current
      researches, such as inadequate depth, limited breadth and not so up-to-date
      research focus. The mediocre research level and the phenomena of some
      contradictory results among studies also need being concerned. Therefore,
      progress may be attained if a holistic, dynamic and networked study is conducted
      on the influence of acupuncture on cytokines by combining the latest progress in
      the mechanisms of network of cytokines and neuroendocrine immune network, and
      high throughput cytokine capture assay. In this way, the mechanism of cytokines
      in multi-targets (such as local joints, peripheral blood circulation, central
      nervous system) involving the effects of acupuncture in improving RA will be
      known more.

PMID- 29071953
TI  - [Current Status of Researches on Brain-imaging Responses of Acupuncture
      Stimulation Based on Functional Magnetic Resonance Imaging].
AB  - Using functional magnetic resonance imaging (fMRI) to investigate the underlying
      mechanisms of acupuncture therapy attracts an increasing attention nowadays. In
      the present article, the authors make a brief analysis on the progresses of
      researches about the intra-brain responses of acupuncture stimulation following
      collecting original research papers with key words of "acupuncture","fMRI" and
      "magnetic resonance imaging" in PubMed and CNKI databases from January 2003 to
      December 2014. As a result, a total of 253 original research articles were
      collected. We found that:1) in the past 10 years, the amount of fMRI studies on
      acupuncture is growing; 2) most of these studies (183) are conducted in healthy
      subjects, and fewer studies (44) conducted in patients with problems of
      neurology, psychonosology, gastroenterology, circulation system, pediatrics,
      myopia and dermatology, or with pain; 3)a larger population of studies are
      designed to reveal the specificity of responses of acupuncture point stimulation,
      and fewer focus on analyzing the regularities of acupuncture points combination.
      The authors suggest that the coming acupuncture-neuroimaging studies need to
      expand the research ranges or contents, and improve experimental designs, data
      analysis and quality control (for example, reducing differences of baseline data,
      age span, psychological state, etc., and increasing sample size, etc).

PMID- 29071954
TI  - [Protective Effect of Acupuncture Serum Derived from Acute Convulsion Rats on
      Cultured Hip-pocampal Neurons with Seizure-like Discharges by Regulating
      Expression of Endoplasmic Reticulum Stress-inducible Molecular Chaperones].
AB  - OBJECTIVE: To observe the effect of acupuncture serum on the number of apoptosis
      of the cultured hippocampal neurons with seizure-like discharges and the
      expression levels of endoplasmic reticulum stress-inducible molecular chaperones
      glucose-regulated protein 78 (GRP 78), C/EBP homologous protein (CHOP) and
      cysteine protease protein-12(Caspase-12), so as to reveal its protective
      mechanism on seizure-induced injury of hippocampal neurons. METHODS: A regular
      primary culture of neurons derived from the hippocampus of the newly-born SD rats
      was conducted for 10 days, then these cultured neurons that displayed seizure
      like discharges in Mg2+-free medium were divided into normal extracellular fluid
      (medium) group (normal), Mg2+-free medium group, acupuncture serum group and non
      acupuncture serum group (n=30). Blood examples were taken from pentylenetetrazol
      (i.p.i.) -induced acute convulsion adult SD rats underwent manual acupuncture
      stimulation of "Baihui" (GV 20) and "Dazhui" (GV 14, once daily for 7 days) to
      prepare acupuncture serum. Hippocampal neuronal cultures were prepared from hip
      pocampal tissue isolated from 24 h-old SD rats. The isolated neurons were
      incubated normally in Dulbecco's Modified Eagle Me-dium (DMEM)/Nutrient Mixture F
      12(1:1) for 10 days, followed by exposure to the extracellular fluid {composed of
      NaCl, KCl, CaCl2, MgCl2, HEPES[4-(2-hydroxyethyl)-1-piperazineethanesulfonic
      acid], D-glucose and aminoethanoic acid (pH 7.3)} for 3 h and returned to normal
      culture for normal group, by exposure to Mg2+-free extracellular fluid (to induce
      seizure-like discharges) for 3 h and returned to normal culture for Mg2+-free
      medium group, by exposure to Mg2+-free extracellular fluid for 3 h and returned
      to a regular culture medium[DMEM/F 12(1:1)] plus acupuncture serum (9:1) for
      acupuncture serum group, and by exposure to Mg2+-free extracellular fluid for 3 h
      and returned to DMEM/F 12(1:1) plus non-acupuncture serum (9:1) for non
      acupuncture serum group. The cell apoptosis was assessed at 2, 12 and 48 h after
      application of acupuncture serum or non-acupuncture serum by using TUNEL method
      and the expression levels of GRP 78, CHOP and Caspase-12 proteins of the cultured
      cells at the 3 time-points detected using Western blot. RESULTS: The number of
      apoptotic hippocampal neurons was significantly higher in the Mg2+-free medium
      group than in the normal medium group at 2, 12 and 48 h (P<0.01), and
      considerably decreased in the acupuncture serum group (but not in the non
      acupuncture serum group) relevant to the Mg2+-free medium group at the same time
      points after application of acupuncture serum (P<0.05, P<0.01). The expression
      levels of GRP 78 protein at 2 h, CHOP and Caspase-12 proteins at 2, 12 and 48 h
      were significantly up-regulated in the Mg2+-free medium group relavant to the
      normal me-dium group (P<0.05, P<0.01). After application of acupuncture serum to
      the culture medium, the expression levels of GRP 78 protein at the three time
      points were significantly increased in comparison with the Mg2+-free medium group
      (P<0.01,P<0.05), while those of CHOP at 12 and 48 h, and Caspase-12 at the three
      time-points were notably down-regulated (P<0.05,P<0.01). No significant
      differences were found between the non-acupuncture serum and Mg2+-free medium
      groups in the expression levels of GRP 78, CHOP and Caspase-12 proteins at the
      three time-points (P>0.05). CONCLUSIONS: Acupuncture serum can significantly
      reduce apoptosis of the cultured hippocampal neurons, which may be related to its
      effects in increasing the expression of GRP 78 protein and down-regulating the
      expression of CHOP and Caspase-12 proteins, suggesting an important role of
      acupuncture serum in maintaining the stability of the neuronal endoplasmic
      reticulum.

PMID- 29071955
TI  - [Effect of Acupuncture at "Taichong"(LR 3) and "Neiguan"(PC 6) on Blood Pressure
      and Contents of Aspartic Acid and Glutamic Acid in the Rostral Ventrolateral
      Medulla in Spontaneous Hypertension Rats].
AB  - OBJECTIVE: To explore the potential mechanism of acupuncture stimulation of
      "Taichong" (LR 3) and "Neiguan" (PC 6) in spontaneous hypertension rats (SHR) by
      investigating its effects on blood pressure and contents of aspartic acid(Asp)
      and glutamic acid (Glu) in the rostral ventrolateral medulla (RVLM) region.
      METHODS: A total of 75 SHR were randomized into model group, Taichong (LR 3)
      group, Neiguan (PC 6) group, LR 3+non-acupoint group and LR 3 + PC 6 group (n=15
      rats in each group), and 15 Wistar rats of the same age were used as the normal
      control group. The filiform needles were inserted into the abovementioned
      acupoints and non-acupoint, twirled for a while and then retained for 30 min. The
      treatment was conducted once per day, 15 times in total. The rats' tail blood
      pressure was examined on day 1, 3, 7 and 15 after acupuncture treatment by using
      a non-invasive blood pressure monitor. At the end of experiment, the contents of
      Asp and Glu in the RVLM were detected by high-performance liquid chromatography
      with UV technique. RESULTS: On day 1, 3, 7 and 15 after the acupuncture
      treatment, the raised systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and mean arterial blood pressure (MBP) of PC 6, LR 3, LR 3 + non-acupoint
      and LR 3 + PC 6 groups were all decreased significantly compared with the model
      group (P<0.05). On day 15, the effect of the LR 3 + PC 6 group was significantly
      superior to that of the LR 3, PC 6, and LR 3 + non-acupoint groups in reducing
      the levels of SBP, DBP, and MBP (P<0.05).Compared with the normal control group,
      the contents of Asp and Glu in RVLM were significantly higher in the model group
      (P<0.05). After acupuncture intervention, both Asp and Glu levels in the PC 6, LR
      3, LR 3 + non-acupoint, and LR 3 + PC 6 groups were markedly lower in comparison
      with the model group (P<0.05), and those of the LR 3 + PC 6 group were notably
      lower than those in the LR 3 and PC 6 groups (P<0.05). CONCLUSIONS: Acupuncture
      stimulation of PC 6, LR 3, LR 3 + non-acupoint and LR 3 + PC 6 (in particular) is
      effective in lowering blood pressure in spontaneous hypertension rats, which may
      be associated with its effects in lowering Asp and Glu contents in RVLM.

PMID- 29071956
TI  - [Effect of Electroacupuncture at "Weiwanxiashu" (EX-B 3) on Islet Morphology and
      the Expression of Pancreatic Glucagon-like Peptide-1 Receptor in Type 2 Diabetes
      Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on pancreatic
      glucagon-like peptide-1 receptor (GLP-1 R), pancreatic and duodenal homeobox 1
      (PDX-1) protein expression and blood glucose in type 2 diabetes rats, so as to
      explore the underlying mechanism of EA treatment in improving type 2 diabetes.
      METHODS: Sprague-Dawley rats were randomly divided into blank control group,
      model group, "Weiwanxiashu" (EX-B 3) group, "Xinshu" (BL 15) group, and "Shenshu"
      (BL 23) group, 12 rats in each group. Diabetes model was established by feeding
      the rat with high fat and high sugar diet combined with intraperitoneal injection
      of streptozotocin (35 mg/kg). All the EA groups received 2 Hz, 2 mA continuous
      wave treatment for 20 min everyday, 6 times per week lasting for 4 weeks. Fasting
      blood glucose was measured by Roche glucometer before and after treatment.
      Hematoxylin and eosin (HE) staining and Masson staining were used to detect
      pancreas morphology. GLP-1 R and PDX-1 protein expressions in the pancreas were
      detected by Western blot. RESULTS: Compared to the blank control group, fasting
      blood glucose was significantly increased in the model group(P<0.01), accompanied
      with shrunken islet area, reduced nucleus counts of islet beta cells, and
      compensatorily enlarged beta cell nucleus. Compared to the model group, EA
      intervention significantly reduced fasting blood glucose level only in the EX-B 3
      group (P<0.05), partly restored pancreas morphology and nucleus counts of islet
      beta cells in the EX-B 3, BL 15, and BL 23 groups. Compared to the blank control
      group, GLP-1 R and PDX-1 expressions were decreased in the model group (P<0.01),
      while EA treatment could obviously increase GLP-1 R expression in the EX-B
      3(P<0.01), BL 15 (P<0.01) and BL 23 (P<0.05) groups compared with the model
      group. The expression of GLP-1 R in the BL 15 group was the highest among the
      three EA groups (P<0.05,P<0.01), and that in the EX-B 3 group was higher than in
      the BL 23 group (P<0.05).There were no signifincant differences in the expression
      of PDX-1 protein among the three EA groups (P>0.05). CONCLUSIONS: EA treatment at
      EX-B 3 can reduce blood glucose via regulating pancreas function, increasing
      pancreatic GLP-1 R expression, and partly restoring the morphology of pancreas.

PMID- 29071957
TI  - [Experimental Study for the Treatment of Asthenozoospermia by Electroacupuncture
      in Rats].
AB  - OBJECTIVE: To investigate the effects of different electroacupuncture (EA)
      parameters for the treatment of asthenozoospermia in rats. METHODS: One hundred
      and five male Sprague-Dawley rats were randomly divided into 2 Hz-EA treatment
      daily in 3 d group (n=9), sham-EA group (n=10), model group (n=10); 2 Hz-EA
      treatment every other day in 5 d group, sham-EA group, model group (8 rats in
      each group); 2 Hz-EA treatment every other day in 9 d group, sham-EA group, model
      group (10 rats in each group); 100 Hz-EA treatment every other day in 9 d group
      (n=7), sham-EA group (n=8), model group (n=7). Asthenozoospermia model was
      established by intragastric administration of ornidazole (ORN,400 mg.kg-1.d-1)
      once daily till the end of treatment. EA treatments (2 Hz or 100 Hz) were applied
      to "Shenshu" (BL 23,bilateral), "Zusanli" (ST 36, bilateral) for 30 min,
      intensity of 1-2-3 mA (increasing 1 mA per 10 min), once a day or once every
      other day for 3 times or 5 times. Sham-EA groups were treated with similar
      procedure except that the output leads of the stimulator were disconnected. The
      sperm density, viability, motility, the number of grade A sperm, and grade A+B
      sperm were examined by computer-assisted sperm analysis. RESULTS: (1) 2 Hz-EA
      treatment daily in 3 d:compared with the model group and the sham-EA group, 2 Hz
      EA treatment once daily had no significant effect on all of the sperm motility
      indexes in the asthenozoospermic rats (P>0.05). (2) 2 Hz-EA treatment every other
      day in 5 d:compared with the model group, EA treatment could increase the sperm
      motility (P<0.05), the number of grade A sperm (P<0.05), and the number of grade
      A+B sperm (P<0.05) in the asthenozoospermic rats. However, compared with the sham
      EA group, EA treatment could only improve the number of grade A+B sperm (P<0.05).
      (3) 2 Hz-EA treatment every other day in 9 d:compared with both the model group
      and the sham-EA group, EA treatment could markedly improve the sperm viability
      (P<0.001), the sperm motility (P<0.001), the number of grade A sperm (P<0.001),
      and the number of grade A+B sperm (P<0.001) in the asthenozoospermic rats. (4)
      100 Hz-EA treatment every other day in 9 days:compared with both the model group
      and the sham-EA group, all of the sperm indexes in the asthenozoospermic rats
      including the sperm viability (P<0.001 vs. the model group, P<0.05 vs. the sham
      EA group), the sperm motility (P<0.001 vs. the model group, P<0.01 vs. the sham
      EA group), the number of grade A sperm (P<0.01) and the number of grade A+B sperm
      (P<0.01) also could be improved after EA treatment. Unexpectedly,none of the EA
      treatment had significant influence on the sperm density in the asthenozoospermic
      rats. CONCLUSIONS: Both 2 Hz-EA and 100 Hz-EA treatment once every other day for
      5 times in 9 d had a therapeutic effect on asthenozoospermia by improving the
      sperm viability and the sperm motility in the rats.

PMID- 29071958
TI  - [Effect of Electroacupuncture on Cerebro-cortex Caspase-3 Expression and Blood
      Lipid Levels in Hyperlipemia Rats with Cerebral Ischemia].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Fenglong" (ST 40), "Sanyinjiao" (SP 6) plus manual acupuncture (MA) stimulation
      of "Shuigou" (GV 26) and "Baihui" (GV 20) on Caspase-3 protein expression in the
      cerebral cortex of rats with hyperlipemia and cerebral ischemia(HL-CI),so as to
      reveal its mechanisms underlying improvement of HL-CI. METHODS: Forty-five rats
      were randomly divided into normal control,sham operation,model,EA group I(EA+MA
      was given for 14 days, i.e., 7 days before CI, and 7 days more after HL-CI)and EA
      group II (EA+MA was given for only 7 days after HL-CI),with 9 rats being in each
      group. The HL-CI model was established by feeding the animals with high fat
      forage for 6 weeks and then making an occlusion of the unilateral middle cerebral
      artery by regional application of quantitative paper adsorbing 50% FeCl3 solution
      (10 MUL). Rats of the sham operation group were treated with the same procedures
      only without application of FeCl3 solution. For rats of the EA group I,EA (1-3
      mA, 2 Hz/100 Hz) was applied to bilateral acupoints SP 6 and ST 40 (for 20
      min),and MA stimulation applied to GV 26 and GV 20. EA was conducted once daily
      for 7 days after 6 weeks' high fat fo-rage feeding, and EA+MA intervention was
      conducted once daily for 7 days after CI modeling. For rats in the EA group II,
      EA+MA was applied to the same 4 acupoints once a day for 7 days only after CI
      modeling. The neurological impairment was assessed by Zea Longa's scoring. The
      blood sample was taken from the abdominal aorta for measuring the contents of
      serum cholesterol (CHO),triglyceride (TG) and high-density lipoprotein
      cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Pathological
      changes of the cerebral cortex were observed after H.E. staining, and the
      expression of cerebro-cortex Caspase-3 was analyzed by immunohistochemistry.
      RESULTS: Following modeling,the neurological score,CHO, TG and LDL-C contents,
      and the number of Caspase-3 positive cells as well as Caspase-3 immunoactivity
      level were significantly increased in the model group(P<0.05), while serum HDL-C
      level was obviously decreased(P<0.05). After the treatment,the increased
      neurological score, CHO, TG and LDL-C contents, and the number of Caspase-3
      positive cells and Caspase-3 immunoactivity level were considerably decreased in
      the EA group I and II(P<0.05)while the decreased HDL-C level was notably
      increased relevant to the model group(P<0.05). The effects of the EA group I were
      notably superior to those of EA group II in down-regulating the neurological
      score,CHO, TG and LDL-C levels and the expression of Caspase-3 protein(P<0.05).
      No significant differences were found between the normal control and sham
      operation groups in the neurological scores 20 min and 7 days after modeling and
      Caspase-3 expression levels (P>0.05). H.E. staining showed a reduction of the
      apoptotic cells and inflammatory cells in both EA group I and II. CONCLUSIONS:
      Both EA and EA+MA interventions can improve neurological function in HL-CI
      rats,which may be related to their effects in adjusting the levels of serum
      lipids and down-regulating the expression of cell apoptosis-related Caspase-3
      protein in the ischemic cortex. Moreover, the cerebral ischemia injury may be
      lightened by EA-lowering hyperlipemia first.

PMID- 29071959
TI  - [Effect of Electroacupuncture Intervention on Expressions of Nerve Growth Factor
      and Growth Arrest-specific Protein 7 in Ventral Posterolateral Thalamic Nucleus
      in Cerebral Ischemia Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture(EA) on expressions of
      nerve growth factor(NGF) and growth arrest-specific protein 7(Gas 7) in the right
      ventral posterolateral nucleus(VPL) in the focal cerebral ischemia (FCI) rats, so
      as to explore its possible mechanism underlying improvement of secondary injury
      of FCI. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into
      normal group, sham operation group, model group and electroacupuncture (EA) group
      (n=12 in each group) by random number table.The FCI model was made by occlusion
      of the right middle cerebral artery (MCAO) with thread embolus.One week after
      MCAO, EA(2 Hz,2 V) was performed on "Baihui"(GV 20) and left "Zusanli"(ST 36) for
      30 min,once daily for successively 21 days.The expressions of NGF and Gas 7 in
      the right VPL were detected by immunohistochemistry (n=6 in each group) and
      Western blot (n=6 in each group), respectively;meanwhile Nissl staining was
      conducted to show VPL neurons. RESULTS: Nissl staining showed that the structure
      of right VPL was clear and complete,and the nuclei were centered and clear in the
      normal group and sham operation group;the VPL neurons were deeply stained, and
      the nuclei were pyknotic in the model group;the morphology of neurons in the EA
      group was similar to that of the normal group. The results of
      immunohistochemistry and Western blot were consistent. Expressions of NGF and Gas
      7 proteins in the right VPL were not of significant differences between the sham
      operation group and the normal group (P>0.05). Compared with the normal group,
      the expressions of NGF and Gas 7 proteins in the VPL of the ischemic side were
      significantly increased in the model group(P<0.05). After treatment,the
      expression levels of NGF and Gas 7 proteins were further up-regulated in the EA
      group in comparison with the model group(P<0.05). CONCLUSIONS: The enhanced
      expressions of NGF and Gas 7 in the ischemic VPL of FCI rats may be involved in
      the neuroprotection and repairing; EA can significantly up-regulate the
      expressions of NGF and Gas 7 in VPL of the ischemic side, which may contribute to
      its effect in improving secondary thalamic impairment of FCI.

PMID- 29071960
TI  - [Comparison of Protective Effect of Electroacupuncture on Myocardial Ischemia
      Injury Between Different Acupoint Formulas in Rats].
AB  - OBJECTIVE: To observe the different effects of electroacupucnture of "Neiguan"
      (PC 6) grouping with other acupoints on myocardial ischemia (MI) injury, so as to
      provide evidence for clinical acupoint formulas. METHODS: Forty Wistar male rats
      were randomly divided into normal, model, EA 1[bilateral "Neiguan" (PC 6),
      bilateral "Zusanli" (ST 36),"Guanyuan" (CV 4)], and EA 2[bilateral "Neiguan" (PC
      6), bilateral "Shenmen" (HT 7), "Danzhong" (CV 17)] groups, 10 rats in each
      group. The MI model was established by subcutaneous injection with ISO solution(5
      mL/kg), once per day for 7 days. Both EA 1 and EA 2 groups were subjected to EA
      (2 Hz/100 Hz, 1 mA) for 10 min before subcutaneous injection, once daily for 21
      days. Electrocardiogram (ECG) was recorded after treatment. Serum cTnT was
      detected by biochemistry. SOD, GSH-Px and MDA in myocardial tissues of left
      ventricular were measured by ELISA, and the ultrastructural changes of myocardial
      cells in the left ventricular were observed by electron microscope. RESULTS:
      Compared with the normal group, the amplitude of S-T segment and HR of ECG, cTnT
      and MDA contents were significantly increased in the model group (P<0.01)
      accompanied with seriously destroyed ultrastructure in the myocardial tissue,
      while SOD and GSH-Px levels were lower than those in the normal group (P<0.01).
      However, EA treatments reversed all the abnormal changes in the model group
      (P<0.05). There was no significant difference between EA 1 and EA 2 groups in the
      amplitude of S-T segment and HR (P>0.05); cTnT and MDA levels in the EA 1 group
      were lower than those in the EA 2 group (P<0.05), while SOD and GSH-Px levels
      were higher than those in the EA 2 group (P<0.05), accompanied with lighter
      degree of ultrastructure damage in the myocardial tissue in the EA 1 group.
      CONCLUSIONS: EA can prevent myocardial ischemic injury, and the effect of EA 1
      treatment was better than that of EA 2.

PMID- 29071961
TI  - [Effect of Electroacupuncture at "Yintang" (GV 29) and "Tianshu" (ST 25) on the
      Ethology and the Expression of TRPV 1 Receptor in Colon of Irritable Bowel
      Syndrome Rats].
AB  - OBJECTIVE: To observe the ethology and expression of transient receptor potential
      vanilloid-1(TRPV 1) in colon of irritable bowel syndrome (IBS) rats treated by
      electroacupuncture (EA) at "Yintang" (GV 29) and "Tianshu" (ST 25), so as to
      explore the different effectiveness of different acupoints and its related
      mechanism underlying improvement of the symptoms of somatopsychic illness.
      METHODS: Thirty-two neonatal Wistar rats were randomly divided into blank control
      group, model group, Yintang (GV 29) group, and Tianshu (ST 25) group (n=8 in each
      group). IBS model was established by neonatal maternal separation and acetic acid
      enema combined with colon and rectum expansion stimulation. Rats of the GV 29 and
      ST 25 groups were given EA treatment at age of 9 weeks old, 20 minutes, once
      every other day for 5 times. Latency of the 1st time contraction wave and numbers
      of contractive wave in 90 s were recorded to evaluate abdominal visceral
      sensitivity by abdominal withdrawal reflex. Horizontal and vertical movements
      were observed to assess the emotional and psychological behavior of rats by open
      field test. TRPV 1 expression in colon was detected by immunohistochemistry
      method. RESULTS: Compared with the black control group, latency of the 1st time
      contractive wave was significantly shortened and the wave numbers in 90 s were
      increased significantly in the model group (P<0.01), while the numbers of
      vertical and horizontal movements were also significantly reduced (P<0.01),
      accompanied with increased TRPV 1 expression in the colon (P<0.05). Compared with
      the model group, After EA intervention, the levels of the above-mentioned 5
      indexes were significantly reversed in the GV 29 and ST 25 groups
      (P<0.01,P<0.05), except the number of horizontal movement in the ST 25 group
      (P>0.05). The expression level of TRPV 1 was significantly lower in the ST 25
      group than in the GV 29 group (P<0.01). CONCLUSIONS: EA at GV 29 and ST 25 can
      alleviate the abdominal pain and improve the mental and emotional disorders in
      IBS rats. GV 29 has a better effect on relieving the depressive-like
      psychoemotional behavior of IBS rats, while ST 25 is more effective in treating
      abdominal pain. There is significantly different influence on TRPV 1 expression
      in colon between these two treatment groups, which may contribute to their
      different effect in pain relieving.

PMID- 29071962
TI  - [Effect of Acupoint Injection on Eosinophil Counts,Protein and mRNA Expressions
      of Eotaxin in Nasal Mucosa of Allergic Rhinitis Rats].
AB  - OBJECTIVE: To observe the effect of acupoint injection on eosinophils (EOS)
      counts and expression of eotaxin in nasal mucosa of allergic rhinitis (AR) rats,
      so as to reveal its mechanism underlying improving AR. METHODS: Twenty-four
      Sprague-Dawley (SD) rats were randomly divided into normal, model and acupoint
      injection groups (n=8 in each group). The AR model was established by
      intraperitoneal injection of ovalbumin sensitization. Bilateral "Yingxiang"(LI
      20) and "Yintang"(GV 29) were selected for acupoint injection of the mixture
      solution of lidocaine, dexamethasone, and transfer factor (0.1 mL/acupoint) on
      the 1st, 5th, 9th, and 13th day after AR model established, a total of four
      times. EOS in the nasal mucosa was counted under light microscope after HE
      staining. Protein and mRNA expressions of eotaxin in the nasal mucosa were
      detected by immunohistochemical and RT-PCR methods, respectively. RESULTS:
      Compared with the normal group, EOS counts, protein and mRNA expressions of
      eotaxin in the nasal mucosa were significantly higher in the model group
      (P<0.05). Compared with the model group, EOS counts, protein and mRNA expressions
      of eotaxin in the nasal mucosa were significantly lower in the acupoint injection
      group (P<0.05). CONCLUSIONS: Acupoint injection can reduce the nasal mucosa
      inflammation by suppressing the protein and mRNA expressions of eotaxin,
      decreasing the infiltration and gathering of EOS in the nasal mucosa.

PMID- 29071963
TI  - [Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in
      the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea
      Pigs].
AB  - OBJECTIVE: To observe the expression of catechol-O-methyltransferase (COMT) in
      inferior colliculus and auditory cortex of guinea pigs with age-related hearing
      loss(AHL) induced by D-galactose, so as to explore the possible mechanism of
      electroacupuncture(EA) underlying preventing AHL. METHODS: Thirty 3-month-old
      guinea pigs were randomly divided into control group, model group and EA
      group(n=10 in each group), and ten 18-month-old guinea pigs were allocated as
      elderly group. The AHL model was established by subcutaneous injection of D
      galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for
      15 min in the EA group while modeling, once daily for 6 weeks. After treatment,
      the latency of auditory brainstem response(ABR) III wave was measured by a brain
      stem evoked potentiometer. The expressions of COMT in the inferior colliculus and
      auditory cortex were detected by Western blot. RESULTS: Compared with the control
      group, the latencies of ABR III wave were significantly prolonged and the
      expressions of COMT in the inferior colliculus and auditory cortex were
      significantly decreased in the model group and the elderly group(P<0.05). After
      the treatment, the latency of ABR III wave was significantly shortened and the
      expressions of COMT in the inferior colliculus and auditory cortex were
      significantly increased in the EA group in comparison with the model group
      (P<0.05). CONCLUSIONS: EA at "Yifeng" (SJ 17) and "Tinggong" (SI 19) can improve
      the hearing of age-related deafness in guinea pigs, which may contribute to its
      effect in up-regulating the expression of COMT in the inferior colliculus and
      auditory cortex.

PMID- 29071964
TI  - [Effect of Moxibustion on Serum IL-17 and TNF-alpha Levels in Collagen-induced
      Arthritis Rats].
AB  - OBJECTIVE: To observe the influence of moxibustion on serum interleukin -17 (IL
      17) and tumor necrosis factor alpha (TNF-alpha) levels in collagen-induced
      arthritis (CIA) rats, so as to study its mechanism underlying improvement of
      rheumatoid arthritis. METHODS: A total of 40 male Wistar rats were used in the
      present study, and 8 rats were randomly selected as a normal control group. The
      other 32 rats were modeled. The primary immunity emulsion was made with mixed
      Type II chicken collagen and complete Freund's adjuvant, and 0.3 mL emulsion
      (containing 0.3 mg collagen) was injected equally into left pelma, tail root and
      the back. Seven days after the primary immune, the same procedure was conducted
      to induce the secondary immunity, and the emulsion was made with mixed Type II
      chicken collagen and incomplete Freund's adjuvant. The whole course of mo-deling
      lasted 21 days. And then 24 CIA rats were randomly divided into model group,
      medication group and moxibustion group (n=8 in each group). For those of the
      moxibustion group, suspended moxibustion with 20 mm distance above "Zusanli"(ST
      36)and "Kunlun" (BL 60) was performed for 20 min/acupoint, once daily,
      alternately on left and right hind limbs for 10 consecutive days. For those of
      the medication group, gavage of methotrexate (0.1 mg/100 g) was administrated
      once every 5 days, and totally two times. Left ankle joint diameter and body
      weight were detected, and X-ray of left tarsus was observed in each group before
      and after modeling or after treatment. Serum levels of IL-17 and TNF-alpha were
      determined by ELISA kits. RESULTS: After modeling, the left ankle diameter and
      serum concentrations of IL-17 and TNF-alpha increased (P<0.05), and the body
      weight decreased (P<0.05) in the model group compared to the control group,
      combined with the tarsus soft tissue swelling, joint space narrowing, bone
      destruction seen from the tarsal X-ray. After intervention, the ankle diameter,
      the serum IL-17 and TNF-alpha levels decreased (P<0.05), and the body weight
      increased (P<0.05) in both medication and moxibustion groups compared to the
      model group; meanwhile the tarsus soft tissue swelling and the bone deformity
      turned to be improved. There were no significant differences between the
      medication group and the moxibustion group in above mentioned indexes (P>0.05).
      CONCLUSIONS: Moxi-bustion is effective in CIA rats, and the mechanism may be
      related to the reduction of serum IL-17 and TNF-alpha levels.

PMID- 29071966
TI  - [Effects of Moxibustion at "Feishu"(BL 13) and "Shenshu"(BL 23) on Peripheral
      Blood T Cells and Serum Interleukin in Asthmatic Rats].
AB  - OBJECTIVE: To observe the effect of moxibustion at "Feishu" (BL 13) and
      "Shenshu"(BL 23) on peripheral blood T cells and serum interleukin in rats with
      asthma, so as to explore its immunological mechanisms in relieving asthma.
      METHODS: Thirty SD rats were randomly divided into normal, model and moxibustion
      groups(10 rats/group). Asthma model was established by intraperitoneal injection
      of ovalbumin and aluminum hydroxide, and ovalbumin inhalation. Moxibustion was
      applied to bilateral "Feishu" (BL 13) and "Shenshu"(BL 23) for 30 min, once daily
      for 14 d. The pathologic changes of the lung tissue were detected by H.E.
      staining. The levels of CD 3+, CD 4+, CD 8+ T cells in whole blood were detected
      by flow cytometry. Serum IgE, IL-1 beta, IL-1 Ra contents were assayed by ELISA
      (enzyme-linked immunosorbent assay). RESULTS: The thickened muscle of bronchial
      wall, mucosal edema, infiltration of inflammatory cells and partial destruction
      of the alveolar structure were found in the model group. While in the moxibustion
      group, the structure of the alveolar wall was complete, the morphology of the
      bronchioles was regular, and there were no mucus plug formation and epithelial
      cell shedding in the lumen. The contents of blood CD 8+ and CD 3+ T cells, and
      serum IgE and IL-1 beta in the model group were obviously higher than those in
      the normal group (P<0.01). Compared with the model group, the levels of blood CD
      8+ T cell, serum IgE and IL-1 beta in the moxibustion group were all decreased
      (P<0.05,P<0.01), meanwhile the levels of blood CD 4+ T cell and serum IL-1 Ra
      were increased (P<0.01,P<0.05). CONCLUSIONS: Moxibustion can reduce the levels of
      serum IgE and IL-1 beta, and increase the level of serum IL-1 Ra, which may play
      an important role in the treatment of asthma.

PMID- 29071965
TI  - [Inhibitory Effect of Acupoint Application on Airway Remodeling and Expression of
      TGF-beta 1/Smad 3 in the Lung Tissue of Chronic Asthma Mice].
AB  - OBJECTIVE: To observe the effect of acupoint application on transforming growth
      factor (TGF)-beta 1/Smad 3 signaling pathway, so as to reveal its mechanism
      underlying improvement of airway remodeling in chronic asthma mice. METHODS:
      BALB/c mice were randomly divided into normal group,model group,sham acupoint
      application group (sham group),acupoint application group, and dexamethasone
      group (n=8 in each group). The chronic asthma model was established by
      intraperitoneal injection of ovalbumin sensitization. The acupoint application
      group was treated with plaster composed with White Mustard Seed, Rhizoma
      Corydalis, Unprocessed Radix Kansui, and Herba Asari, on bilateral "Feishu" (BL
      13), "Xinshu" (BL 15) and "Geshu" (BL 17) points, 6 hours a day for 14 days. The
      sham group was treated with plaster containing vaseline on bilateral BL 13, BL 15
      and BL 17, 6 hours a day for 14 days. The dexamethasone group was treated with
      dexamethasone 1 mg.kg-1.day-1 intraperi-toneally, once daily for 14 days. At the
      end of treatment, airway resistance was detected by mouse lung function
      instrument. Patho-logical changes of airway were observed under light microscope
      after hematoxylin-eosin staining, and the morphological parameters were measured
      by image analysis software. Immunohistochemistry method was used to detect the
      expression of TGF-beta 1 and Smad 3 in the lung tissue of mice. RESULTS: Compared
      with the normal group, the airway resistance, the total bronchial wall area
      (WAt)/lumen perimeter (Pi), the smooth muscle wall area (WAm)/Pi, and the
      expression of TGF-beta 1 and Smad 3 in the lung tissues were significantly higher
      in the model and sham groups (P<0.01). Compared with the model group and the sham
      group, the airway resistance, WAt/Pi, WAm/Pi, the expression of TGF-beta 1 and
      Smad 3 in the lung tissues were decreased in the acupoint application group and
      the dexamethasone group (P<0.05). There were no significant differences between
      the acupoint application group and the dexamethasone group in the above mentioned
      indexes (P>0.05). CONCLUSIONS: Acupoint application can improve airway remodeling
      by down-regulating the expression of TGF-beta 1/Smad 3 in the airway of chronic
      asthmatic mice.

PMID- 29071967
TI  - [Efficacy of Modified Acupuncture Method at Renying (ST 9) for Patients with
      Cervical Spondylosis of Vertebral Artery Type and Its Impact on Velocity of
      Cervical Blood Flow].
AB  - OBJECTIVE: To observe the clinical efficacy of modified acupuncture at Renying
      point (ST 9) for patients with cervical spondylosis of vertebral artery type and
      its influence on velocity of cervical blood flow. METHODS: Fifty-nine cases of
      vertebral artery type cervical spondylosis were randomly divided into control
      group (n=30) and treatment group (n=29). Both groups were acupunctured at ST 9,
      with routine acupuncture technique used in the control group and modified
      technique in the treatment group, respectively. All cases received two courses of
      treatment, each course covered consecutive 6 once-per-day treatments. Before and
      after treatment, transcranial Doppler (TCD) was used to measure the systolic peak
      blood flow velocity (Vs) of left vertebral artery (LVA), right vertebral artery
      (RVA) and basilar artery (BA), and the scores of "cervical vertigo symptoms and
      functional assessment scale" (CVSFAS) were also assessed, separately. RESULTS:
      CVSFAS scoring, Vs of LVA, RVA and BA after treatment showed significant
      improvement compared with those before treatment (P<0.01, P<0.05). The efficacy
      of the treatment group in the above mentioned indexes was superior to that of the
      control group (P<0.05). The total effective rate of the treatment group was 93.1%
      (27/29), superior to 70.0% (21/30) of the control group (P<0.05). CONCLUSIONS:
      The modified acupuncture method at ST 9 is clinically effective in the treatment
      of cervical spondylosis of vertebral artery type via increasing the Vs of
      vertebral-basilar artery, improving the local blood circulation and relieving
      pain.

PMID- 29071968
TI  - [Clinical Trials for Treatment of Stroke Patients with Dysphagia by Vitalstim
      Electroacupuncture Combined with Swallowing Rehabilitation Training].
AB  - OBJECTIVE: To observe the clinical effect of vitalstim electroacupuncture (EA)
      combined with swallowing rehabilitation training in the treatment of stroke
      patients with dysphagia. METHODS: A total of 80 stroke patients with dysphagia
      were randomized into treatment and control groups (n=40 in each group). Patients
      of the control group were treated by regular medication for anti-platelet
      aggregation and anti-coagulation, lipid-lowering, neuroprotection, blood glucose
      control and blood pressure control, etc. and swallowing function rehabilitation
      training, and those of the treatment group treated by EA stimulation of Fengchi
      (GB 20), Jinjin (EX-HN 12) and Yuye (EX-HN 13) with a Vitalstim Electrostimulator
      and manual acupuncture stimulation of Lianquan (CV 23), Tiantu (CV 22) in
      combination with regular medication plus swallowing function training as those
      mentioned in the control group. The EA and manual acupuncture stimulation
      treatment was conducted once daily, 6 times a week and 4 weeks altogether. The
      therapeutic effect was assessed by using Kubota swallowing ability test (6
      levels), dysphagia subscale (0-6 scores) of the neurological deficit degrees,
      videofluorography (VFG) assessment (markedly effective, effective and invalid,
      for evaluating the function and symmetry state of the swallowing movements), and
      the MOS Item Short Form Health Survey (SF-36, 8 minor items of two major aspects
      in physiological function, mental health, emotional function, social function and
      overall health) for assessing the patients' daily-life quality. RESULTS: After
      the treatment, the dysphagia score of the treatment group was signi-ficantly
      lower than that of the control group (P<0.05). VFG outcomes showed that, of the
      two 40 patients in the control and treatment groups, 16 and 23 experienced a
      marked improvement, 20 and 15 were effective, 4 and 2 were ineffective, with the
      markedly effective rate being 40.0% and 57.5%, respectively. The daily-life
      quality scores for physiological function, mental health, emotional function,
      social function and overall health were all notably increased after the treatment
      in both groups, particularly in the treatment group (P<0.05). The therapeutic
      effects of the treatment group were remarkably superior to those of the control
      group in improving dysphagia (showed by dysphagia score and VFG outcomes) and
      life quality. CONCLUSIONS: EA treatment combined with swallowing function
      rehabilitation training is effective in improving swallowing ability and daily
      life quality in stroke patients with dysphagia.

PMID- 29071969
TI  - [Effect of Acupuncture Therapy on Body Compositions in Patients with Obesity].
AB  - OBJECTIVE: To observe the clinical effectiveness of acupuncture intervention in
      weight reduction by modulating body compositions in obesity patients. METHODS: A
      total of 71 obesity patients during weight-loss procedure were allocated to
      acupuncture+nutrition-consultation group (n=40) and simple nutrition-consultation
      group (n=31). The patients of the acupuncture +nutrition-consultation group were
      treated by acupuncture stimulation of Zhongwan (CV 12), Xiawan (CV 10), Tianshu
      (ST 25), Wailing (ST 26), Qihai (CV 6), Guanyuan (CV 4), etc. for 30 min, once
      every other day, 3 times per week, 12 times altogether, and also given with
      weekly nutrition consultation (including subjective query, objective measurement,
      analysis, program for nutrition support) at the same time. The patients of the
      simple nutrition-consultation group were treated by only weekly nutrition
      consultation for 4 weeks. Before and after the treatment, the patients' body
      weight, body mass index (BMI), fat mass, percentage of body fat, muscle mass,
      protein quality, water quality and bone mass were measured by using a composition
      analyzer. RESULTS: After 4 weeks' treatment, the body mass, BMI, fat mass and fat
      percentage in both acupuncture+nutrition-consultation and simple nutrition
      consultation groups were significantly decreased (P<0.01), while the weight
      levels of muscle, protein, bone and water content had no apparent changes
      (P>0.05). The therapeutic effect of acupuncture+nutrition-consultation group was
      markedly superior to that of the simple nutrition-consultation group in
      increasing the improved degrees of body weight, BMI, fat mass and fat percentage
      (P<0.01). CONCLUSIONS: Acupuncture plus nutrition consultation is effective in
      reducing body mass, fat mass and percentage of body fat in obesity patients.

PMID- 29071970
TI  - [Meta-analysis on the Therapeutic Effect of Acupuncture at Meridian Sinew for
      Spastic Paralysis After Stroke].
AB  - OBJECTIVE: To review systematically the clinical effects of spastic paralysis
      after stroke treated with acupuncture at meridian sinew ("Jingjin",
      musculotendon). METHODS: "Meridian sinew" "stroke" and "spasm" were taken as the
      key words to retrieve from the Chinese National Knowledge Infrastracture Database
      (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP),
      Chinese Biomedical Library (CBM), Wanfang Data, PubMed and the Cochrane Library.
      The Cochrane"risk of bias" tool was used to conduct the methodological quality
      evaluation to the literature. RevMan 5.3 software was adopted for Meta-analysis.
      RESULTS: Totally, 13 papers were included, with 820 patients involved. In
      reference to Cochrane Reviewers' Handbook 5.0.2, the randomized controlled trial
      (RCT) risk of bias was assessed and it was unclear for all of the 13 papers. The
      results of Meta-analysis showed that the clinical effect was improved with
      acupuncture at meridian sinew as compared with normal acupuncture
      technique[1total effective rate:OR=3.86, 95% CI (2.67,5.57), Z=7.20, P<0.00001;
      2modified Ashworth spasm scale:OR=4.54, 95% CI (2.91,7.10), Z=6.64, P<0.00001;
      3evaluation of limb motor function with Fugl-Meyer score:MD=4.18, 95% CI (
      0.59,8.94), Z=1.72, P=0.09>0.05]. The publication bias of included papers was not
      obvious and therefore it could be neglected in the impact on the combined effect
      size. CONCLUSIONS: Acupuncture at meridian sinew is effective in the treatment of
      spastic paralysis after stroke. The total clinical effect and the improvement in
      muscular tone with acupuncture at meridian sinew are better than those with
      normal acupuncture technique. The quality of the included literature is not high
      generally. Hence, it is necessary to have more clinical studies with high-quality
      and strict design.

PMID- 29071971
TI  - [Compliance Control Strategy in the Practical Randomized Controlled Trial Study
      of Electroacupuncture Combined with Behavior Control for Overweight and Simple
      Obesity].
AB  - Electroacupuncture (EA) has been extensively used in clinical treatment of
      obesity. The effectiveness relies not only on the correct diagnosis and rational
      treatment, but also on the voluntary cooperation of patients, that is the
      satisfactory compliance. The patient compliance refers to his/her submissiveness
      and executive ability to medical advice, which is the indispensable factor for
      the clinical efficacy. The strength of it depends on the patient himself/herself,
      and moreover is improved through some therapeutic strategies. Based on the
      emphasis of individual treatment in the real world, the practical randomized
      controlled trial (RCT) study pays attention to patient's compliance at the
      beginning of trial design. In this paper, in terms of the influential factors and
      control strategies, the compliance of simple obesity patient in the practical RCT
      study was summarized systematically.

PMID- 29071972
TI  - ["Bell-striking" Saying of Acupuncture Therapy].
AB  - As an analogy, a prototype of "bell-striking" is proposed in the present paper
      for exploring the basic properties, major elements, and potential mechanisms of
      acupuncture stimulation. On the strength of analysis on the physiological basis
      of acupuncture effect, several fundamental aspects of acupuncture are summarized
      as a) the body-surface stimulating characters, b) general and local effects, and
      c) triggering the auto-regulative function of the organism, which mimics the
      "bell-striking" response. Namely, when stroke, bell will chime, otherwise,
      chiming will not be heard. During analyzing special contents of acupuncture
      theory, its formative background should not be separated, and it is improper to
      take, modern medical theory of the human body as the guiding thinking way for
      researching the ancient Chinese medical literature.

PMID- 29071973
TI  - [Transcutaneous Electrostimulation of Auricular Otopoints Reduces Epileptic
      Attack Possibly by Suppressing Hippocampal Gliocyte Proliferation and Regulating
      IL-6 and IL-10 Expression in Chronic Temporal Lobe Epilepsy Rats].
AB  - OBJECTIVE: To observe the effect of transcutaneous otopoint electrostimulaiton
      (TCOES) on seizure frequency, immunoreactivity of hippocampal gliocytes and
      expression of proinflammatory cytokine interleukin-6(IL-6) and anti-inflammatory
      cytokine IL-10 in chronic temporal lobe epilepsy (CTLE) rats, so as to
      investigate its antiepileptic mechanism. METHODS: Thirty-six SD rats were
      randomly divided into control, model and TCOES groups (n=12 in each group). The
      CTLE model was established by intraperitoneal injection (i.p.i.) of lithium
      chloride (127.2 mg/kg), scopolamine (1 mg/kg, 20 h after the 1st injection) and
      pilocarpine (10 mg/kg, 30 min after scopolamine injection). Rats of the control
      group were treated by i.p.i. of normal saline. TCOES (1 mA, 20 Hz) was applied to
      bilateral otopoint "Heart"-"Lung"-"Subcortex" region for 20 min, once daily for 6
      weeks. The epileptic attack was observed by a video monitoring system. The
      numbers of ionized calcium-binding adapter molecule-1 (Iba 1)-labeled
      microgliacytes and glial fibrillary acidic protein (GFAP)-labeled astrocytes in
      the CA 1 and CA 3 regions of hippocampus were counted under light microscope
      after immunostaining, and the expression levels of hippocampal IL-6 and IL-10
      proteins and genes were determined by immunofluorescence and quantitative real
      time PCR, respectively. RESULTS: After TCOES intervention, the seizure frequency
      was significantly decreased in comparison with pre-treatment(P<0.05), modeling
      induced dramatic increase of the numbers of microgliacytes and astrocytes,IL-6
      immunoactivity in the hippocampal CA 1 and CA 3 regions, and IL-6 mRNA expression
      in the hippocampus were significantly suppressed (P<0.05), and hippo-campal IL-10
      immunoactivity and mRNA expression were considerably up-regulated in comparison
      with the model group (P<0.05). CONCLUSIONS: TCOES intervention has an
      antiepileptic effect in CTLE rats, which may be associated with its effects in
      suppressing gliocyte proliferation, suppressing the expression of proinflammatory
      cytokine IL-6, and up-regulaiting the expression of anti-inflammatory cytokine IL
      10 in the hippocampus.

PMID- 29071974
TI  - [Effect of "Spleen-Stomach Harmonizing" Needling on Insulin Resistance and
      Expression of Insulin Receptor Substrate-1, -2, and Glucose Transporter-4 in
      Insulin Resistance Type 2 Diabetes Rats].
AB  - OBJECTIVE: To observe the effect of manual acupuncture stimulation of "Quchi" (LI
      11), "Hegu" (LI 4), "Zusanli" (ST 36), etc. with "spleen-stomach harmonizing"
      technique on insulin resistance index (ISI) and the expression of insulin
      receptor substrate-1 (IRS-1), IRS-2 (two upstream key proteins) and glucose
      transporter-4 (GluT-4, downstream key protein) of the phosphatidylinositol 3
      kinase (PI 3 K)/Akt signaling pathway in insulin resistance type 2 diabetes (IRT
      2 D) rats, so as to explore its mechanism underling improvement of type 2
      diabetes. METHODS: A total of 35 male Wistar rats were used in the present study.
      The IRT 2 D model was established by feeding the animal with high-fat and high
      sugar diet for 8 weeks, and subsequent intraperitoneal injection (i.p.i.) of a
      low dose of streptozotocin (25 mg/kg). Using the stratified random sampling
      method, 20 successful IRT 2 D rats were equally divided into model and
      acupuncture groups. Ten normal rats were used as the control group. The bilateral
      acupoints of LI 11, LI 4, ST 36, "Xuehai" (SP 10), "Fenglong" (ST 40),
      "Yinlingquan" (SP 9), "Diji" (SP 8), "San-yinjiao" (SP 6) and "Taichong" (LR 3)
      were punctured with filiform needles, followed by manipulating the needles with
      "spleen-stomach harmonizing" technique. The treatment was given once daily for 4
      weeks except the weekends. Fasting blood glucose and serum insulin levels were
      measured using ELISA. The quadriceps muscle of thigh of each rat was sampled to
      test the expression levels of IRS-1, IRS-2, and GluT-4 proteins and genes with
      Western blot and quantitative Real-time PCR, respectively. RESULTS: Following 4
      weeks' acupuncture intervention, the modeling-induced remarkable increase of ISI,
      and considerable down-regulation of expression levels of IRS-1, IRS-2 and GluT-4
      proteins and genes in the quadriceps femoris were significantly reversed relevant
      to the model group (P<0.01), suggesting a possible activation of PI 3 K/Akt
      signaling after acupuncture administration. CONCLUSIONS: Spleen-stomach
      regulation needling can improve insulin resistance and up-regulate the expression
      of IRS-1, IRS-2 and GluT-4 in the quadriceps femoris in type 2 diabetes rats.

PMID- 29071975
TI  - [Mechanism of Heat-reinforcing Needling for Rheumatoid Arthritis Rabbits with
      Cold Syndrome Based on Metabonomics].
AB  - OBJECTIVE: To explore the specific mechanism of heat-reinforcing needling (HRN)
      for rheumatoid arthritis (RA) rabbits with cold syndrome based on metabolomics.
      METHODS: A total of 40 healthy rabbits were randomly divided into a normal group,
      a model group, a reinforcing-reducing needling(RRN) group, a twirling-reinforcing
      needling (TRN) group and a HRN group (n=8 rabbits/group). The RA model with cold
      syndrome was established with ovalbumin and freezing. Except the normal and model
      groups, RRN, TRN and HRN were given at "Zusanli" (ST 36) in the corresponding
      acupuncture groups for 30 min, once a day for 7 days. After the interventions,
      the pain threshold and the local skin temperature of each group were observed.
      The endogenous metabolites in the serum were analyzed by the gas chromatography
      mass spectrometry (GC-MS) technology combined with the pattern-recognition
      method. RESULTS: The pain threshold and the local skin temperature in the model
      group were lower than those in the normal group (P<0.05). The pain thresholds and
      the local skin temperatures in the three acupuncture groups were higher than
      those in the model group after interventions (P<0.05), and those in the HRN group
      were obviously higher than those in the RRN and TRN groups (P<0.05). The serum
      metabolites of leucine, valine, isoleucine, and arachidonic acid in the model
      group were increased compared with those in the normal group (P<0.05), and the
      metabolites of alpha-ketoglutaric acid, citric acid, succinic acid, glucose,
      inositol, palmitic acid, stearic acid, lactose, d-ribose, and D-mannose were
      decreased (P<0.05). The above-mentioned metabolites in the three acupuncture
      groups were significantly reversed relevant to the model group (P<0.05), and the
      effect of HRN group was significantly superior to those of the RRN and TRN groups
      in regulating alpha-ketoglutaric acid, citric acid, succinic acid, glucose,
      inositol, d-ribose, and D-mannose (P<0.05). CONCLUSIONS: HRN for RA with cold
      syndrome is effective, which may be related to the specific regulation for the
      krebs cycle and glycometabolism.

PMID- 29071976
TI  - [Hypothalamic Transcription Profiles Associated with Twirling-reducing Needling
      in Rats with Stress-induced Prehypertension].
AB  - OBJECTIVE: To observe the effect of twirling-reducing needling on changes of
      profile of differentially-expressed genes in the hypothalamus in rats with stress
      induced prehypertension (SI-PHT), so as to explore its mechanism under-lying
      improvement of prehypertension. METHODS: Wistar male rats were randomly divided
      into blank control group (n=12), model group (n=12) and acupuncture group (n=10).
      The SI-PHT model was established by planta-electric-shock stimulation (30 V, 5 s)
      plus noise stimulation (80-100 db, 50 ms), twice daily, continuously for 11 days.
      Manual acupuncture stimulation (twirling-reducing needling) was applied to
      bilateral "Taichong" (LR 3) and "Quchi" (LI 11) for about 1 min (60 cycles/min),
      followed by retaining the needles for 20 min during modeling preparation, once
      daily for 11 days. The systolic blood pressure (SBP) and behavior changes were
      recorded before intervention and on the 3rd, 5th, 7th, 9th and 11th day during
      modeling. The expression (Fold change,|FC| >= 1.5) profile of genes in the
      hypothalamus was analyzed using Affymetrix GeneChip Rat Gene 2.0 ST Array,
      followed by analyzing the differentially-expressed genes involving the related
      biological process,molecular function, and signaling pathways by using Gene
      Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), separately.
      RESULTS: After modeling, the systolic pressure levels were remarkably increased
      from the 3rd day to the 11th day in both model and acupuncture groups relatively
      to their respective baseline levels (P<0.01), and were significantly lower in the
      acupuncture group than in the model group (P<0.01) from the 5th day to the 11th
      day. Meanwhile, 93 genes were up-regulated and 153 down-regulated in the model
      group relative to the control group (P<0.05,|FC| >= 1.5), while in comparison
      with the model group, 59 genes were up-regulated and 86 down-regulated in the
      acupuncture group (P<0.05,|FC| >= 1.5). The expression levels of the 40 differen
      tially-expressed genes (24 up-regulated and 16 down-regulated) in the model group
      were evidently reversed after acupuncture stimulation (P<0.05,|FC| >= 1.5). After
      acupuncture stimulation, the expression of acyl-CoA synthetase medium-chain
      family member 3 (Acsm 3) gene was down-regulated, and chorionic gonadotropin
      alpha (Cgalpha), crystal (Cry) alphaB and thyroid stimulating hormone beta
      (Tshbeta) genes and the autoimmune thyroid disease (AITD) pathway were up
      regulated (P<0.05,|FC| >= 1.5), suggesting an involvement of fatty acid
      biosynthetic processing, G-protein coupled receptor protein signaling, and
      hormone activity, etc. in acupuncture-induced blood-pressure lowering.
      CONCLUSIONS: Twirling-reducing needling of acupuncture can lower blood pressure
      in prehypertension rats, which may be related to its effects in regulating
      expression of Acsm 3, Cgalpha, CryalphaB, Tshbeta genes and in activating AITD
      pathway.

PMID- 29071977
TI  - [Effect of Electroacupuncture Intervention on IL-4/STAT 6 and NF-kappaB p 65
      Signaling in Cerebral Cortex in Focal Cerebral Ischemia/Reperfusion Injury Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of
      cerebral cortical interleukin 4 (IL-4), signal transducer and activator of
      transcription 6 (STAT 6) and NF-kappaB family subunit p 65 in focal cerebral
      ischemia/reperfusion injury (CIRI) rats, so as to explore its mechanisms in
      reducing cerebral ischemia. METHODS: Forty-five male SD rats were randomly
      divided into sham group (n=15), CIRI model group (n=15), and EA group (n=15). The
      CIRI model was established by middle cerebral artery occlusion/reperfusion
      (MCAO/R). EA (1 mA, 2 Hz/100 Hz) was applied to "Baihui"(GV 20) and the left
      "Hegu" (LI 4)-"Taichong" (LR 3) for 20 min, once every 12 h, three times
      altogether. The expression levels of p-STAT 6, STAT 6 and NF-kappaB p 65 in the
      ischemic cortex were detected by immunohistochemistry and Western blot,
      separately, and the content of IL-4 was detected by ELISA. RESULTS: Compared with
      the sham group, cerebral IL-4 content and the expression levels of NF-kappaB p 65
      immunoactivity and protein were significantly up-regulated in the CIRI model
      group (P<0.001, P<0.01). Following EA intervention, the levels of IL-4, p-STAT 6
      expression and ratio of p-STAT 6/STAT 6 were notably increased in the EA group
      than in the model group (P<0.01),while the levels of cerebral NF-kappaB p 65
      immunoactivity and protein expression were significantly down-regulated
      (P<0.01,P<0.05). CONCLUSIONS: EA of GV 20 and LI 4-LR 3 can up-regulate cerebral
      cortical IL-4 content and p-STAT 6 expression, and down-regulate NF-kappaB p 65
      expression in CIRI rats, which may contribute to its effect in improving cerebral
      ischemia by reducing inflammatory injury.

PMID- 29071978
TI  - [Effect of "Xingnao Kaiqiao Zhenfa" (Acupuncture Technique for Restoring
      Consciousness) Combined with Rehabilitation Training on Nerve Repair and
      Expression of Growth-associated Protein-43 of Peri-ischemic Cortex in Ischemic
      Stroke Rats].
AB  - OBJECTIVE: To observe the effect of "Xingnao Kaiqiao Zhenfa" (acupuncture
      technique for restoring consciousness) combined with enriched rehabilitation
      training on motor function and expression of growth-associated protein-43 (GAP
      43) of peri-ischemic cortex in ischemic stroke rats, so as to investigate its
      mechanism underlying improvement of ischemic stroke. METHODS: SD rats were
      randomly divided into sham operation, model, rehabilitation and comprehensive
      rehabilitation groups, which were further divided into 3 time-points:7, 14 and 21
      d (n=6 in each). Cerebral ischemia(CI) model was established by occlusion of the
      middle cerebral artery with heat-coagulation. The rehabilitation group was
      treated by enriched rehabilitation training, once a day. The comprehensive
      rehabilitation group was treated by acupuncture combined with enriched
      rehabilitation training. Acupuncture was applied to bilateral "Neiguan"(PC 6) and
      "Shuigou"(GV 26) for 30 min, once a day. The neurological function score, balance
      beam walking test and rotating-rod walking test were evaluated at the end of the
      corresponding treatment time. The expression of GAP-43 in peri-ischemic cortex
      was detected by immunohistochemistry. RESULTS: In comparison with the sham
      operation group, the scores of neurological function, beam walking test and
      rotating-rod walking test were significantly higher in the model group (P<0.01).
      There were no significant changes in the scores of balance-beam walking and
      rotating-rod walking tests in the rehabilitation group compared with the model
      group on day 7 (P>0.05). Compared with the model group at the other time points,
      the scores of neurological function, balance-beam walking test and rotating-rod
      walking test were significantly lower in the rehabilitation and comprehensive
      rehabilitation groups (P<0.05). Compared with the rehabilitation group, the
      scores of neurological function, balance-beam walking test and rotating-rod
      walking test were significantly lower in the comprehensive rehabilitation group
      (P<0.05). In comparison with the sham operation group, the number of GAP-43
      positive cells of peri-ischemic cortex was significantly higher in the model
      group (P<0.01). Compared with the model group, the numbers of GAP-43 positive
      cells of peri-ischemic cortex were significantly increased in the rehabilitation
      and comprehensive rehabilitation groups (P<0.01). The number of GAP-43 positive
      cells of peri-ischemic cortex in the comprehensive rehabilitation group was
      significantly higher than that in the rehabilitation group (P<0.01). CONCLUSIONS:
      "Xingnao Kaiqiao Zhenfa" combined with enriched rehabilitation training can
      promote the recovery of nerve function in ischemic stroke rats, which may be
      associated with its effect in up-regulating the expression of GAP-43 in the peri
      ischemic cortex.

PMID- 29071979
TI  - [Effect of Electroacupuncture Stimulation of Acupoints of Heart Meridian on Brain
      Connectivity in 27 Healthy Volunteer Subjects].
AB  - OBJECTIVE: To observe the changes of brain rest-state functional connectivity
      following electroacupuncture (EA) stimulation of right Xia-Jiquan (HT 1), Shaohai
      (HT 3), Lingdao (HT 4) and Shenmen (HT 7) of the Heart Meridian and non-acupoints
      in healthy volunteers so as to provide an imaging basis for clinical treatment of
      some related disorders. METHODS: A total of 20 healthy volunteers who met the
      inclusion criteria were randomly divided into HT-acupoint group (n=10 cases) and
      non-acupoint group (n=10 cases) according to the visiting sequence. EA (2 Hz, 2-5
      mA) was applied to the right HT 1-HT 3, and HT 4-HT 7 (two outputs of the EA
      stimulator being connected to two acupuncture needle handles) and non-acupoints
      (4 spots on the imaginary mid-line between the HT and the Pericardium Meridian
      apart from the 4 acupoints HT 1-HT 3, and HT 4-HT 7) for 6 min. All the subjects
      underwent resting-state (rs) fMRI using an Achieva 1.5 T magnetic resonance image
      (MRI) scanner before and after EA stimulation. The bilateral posterior cingulate
      was used as the seed point and the functional connectivity data was analyzed by
      using DPARSF software and rs-fMRI data analysis toolkit. RESULTS: After EA
      stimulation of both acupoints and non-acupoints, a similar functional
      connectivity change was found in the bilateral postcentral gyrus, right inferior
      parietal lobule, and right inferior frontal gyrus. After EA of acupoints of the
      HT Meridian, an enhancement of brain functional connectivity was found in the
      left inferior temporal gyrus and right parahippocampal gyrus, and the newly
      activated brain regions were the left precentral gyrus, right precuneus, left
      angular gyrus, left inferior occipital gyrus and the left insula. After EA
      stimulation of non-acupoints, an increased functional connectivity was found in
      the left superior temporal gyrus, which was different from EA of acupoints of HT
      Meridian. CONCLUSIONS: EA stimulation of acupoints of the HT Meridian can enhance
      the rs functional connectivity in some brain regions as the postcentral gyrus,
      inferior temporal gyrus, etc. which is related to mediating information of
      somatosensory, cognitive, affective, memory, cardiovascular activities, etc. in
      healthy volunteer subjects. The only difference between the two EA groups is an
      enhanced functional connectivity found in the left superior temporal gyrus after
      EA of non-acupoints.

PMID- 29071980
TI  - [Effect of Grain-moxibustion on IL-6 and STAT 3 in Inflammatory Microenvironment
      of Lewis Lung Cancer Mice].
AB  - OBJECTIVE: To observe the effect of grain-moxibustion on serum interleukin-6(IL
      6) and signal transducers and activators of transcription 3 (STAT 3) in
      inflammatory microenvironment of Lewis lung cancer mice, so as to explore its
      possible mechanism underlying relieving Lewis lung cancer. METHODS: C 57 BL/6
      mice were randomly divided into blank control group, model group, and moxibustion
      group (n=10 in each group). Lewis lung cancer model was established by hypodermic
      injection of Lewis tumor cell suspension. Mice in the moxibustion group were
      treated by grain-moxibustion at bilateral "Housanli"(ST 36), 5 zhuang each
      acupoint, once a day for 10 days. The body weight, survival state score, volume
      of tumor, and survival rate were observed. Serum IL-6 level was detected by
      ELISA, and the expression of STAT 3 in tumor tissue was determined by Wes-tern
      blot. RESULTS: Compared with the blank control group, the body weight was
      significantly increased in the model group (P<0.05). The volume of tumor
      increased significantly in the model group, while it markedly decreased in the
      moxibustion group after 8 and 10 days treatment compared with the model group
      (P<0.05). The survival state of mice deteriorated companied with decreased
      survival rate in the model group, however, after 6, 8 or 10 days treatment, the
      survival state scores were increased in the moxibustion group than in the model
      group (P<0.05). Compared with the blank control group, both serum IL-6 level and
      STAT 3 expression in tumor tissue were increased significantly in the model group
      (P<0.001). Compared with the model group, both serum IL-6 level and STAT 3
      expression in tumor tissue were decreased significantly in the moxibustion group
      (P<0.001). CONCLUSIONS: Grain-moxibustion has remarkable effect on Lewis lung
      cancer, by improving survival state, reducing death rate, and controlling growth
      rate of tumor, which might be associated with its function of inhibiting the
      activation of IL-6 and STAT 3 in inflammatory microenvironment.

PMID- 29071981
TI  - [Effect of Point-moxibustion and Electroacupuncture on the Expression of
      Endothelial Nitric Oxide Synthase mRNA and Angiotensin 2 mRNA in Gastric Antrum
      in Diabetic Gastroparesis Rats].
AB  - OBJECTIVE: To observe the effect of point-moxibustion and electroacupuncture(EA)
      on gastrointestinal motility, and expression of endothelial nitric oxide
      synthase(eNOS) mRNA and angiotensin 2(AT II) mRNA in gastric antrum in diabetic
      gastroparesis(DGP) rats, so as to reveal the different effect between point
      moxibustion and EA, and explore the mechanism underlying improvement of DGP.
      METHODS: Forty SD rats were randomly divided into normal, model, point
      moxibustion and EA groups, 10 rats in each group. The DGP model was established
      by intraperitoneal injection of streptozotocin (STZ, 2%, 55 mmol/kg) and fed with
      high-sugar and high-fat fodder. "Zusanli" (ST 36), "Sanyinjiao" (SP 6) and
      "Liangmen" (ST 21) were chosen to be stimulated with moxibustion at 0, 10 and 20
      min in the point-moxibustion group or with EA for 20 min in the EA group. The
      treatment was conducted once daily for 15 days. After treatment, blood glucose,
      gastric emptying rate and small intestinal propulsive rate were measured. The
      plasma endothelin 1(ET-1) content was detected by ELISA. The mRNA expression of
      eNOS and AT II in gastric antrum were detected by Real-time PCR. RESULTS:
      Compared with the normal group, the blood glucose in the model group was
      significantly higher (P<0.01). Compared with the model group, the blood glucose
      decreased significantly in the point-moxibustion group and EA group (P<0.05). In
      comparison with the normal group, gastric emptying rate and small intestinal
      propulsive rate were decreased, the content of plasma ET-1 was increased, the
      expression of eNOS mRNA in gastric antrum was significantly reduced and the
      expression of ATII mRNA was significantly increased in the model group(P<0.01).
      In comparison with the model group, gastric emptying rate and small intestinal
      propulsive rate were increased, the content of plasma ET-1 was decreased, the
      expression of eNOS mRNA in gastric antrum was higher and the expression of AT II
      mRNA was significantly lower in both point-moxibustion group and EA group
      (P<0.05), and there were no significant differences between the two treatment
      groups in above mentioned indexes (P>0.05). CONCLUSIONS: Both point-moxibustion
      and EA can effectively promote gastrointestinal motility in DGP rats and improve
      the symptoms of delayed gastric emptying. The two therapies are effective, and
      their mechanism may be related to the increase of eNOS mRNA expression and the
      decrease of AT II mRNA expression in gastric antrum.

PMID- 29071982
TI  - [Effect of Acupuncture on the Expression of Transcription Factor T-bet/GATA-3 in
      Plasma of Rats with Chronic Fatigue Syndrome].
AB  - OBJECTIVE: To observe the effect of acupuncture on the expression of T-box
      expressed in T cell (T-bet)/GATA binding factor-3 (GATA-3) in plasma of rats with
      chronic fatigue syndrome (CFS) and explore the mechanism of acupuncture treatment
      for CFS. METHODS: Forty-eight healthy male SD rats were randomly divided into
      blank control group, CFS model group, acupuncture group, and ginsenoside group
      (12 rats in each group). CFS rat model was established by combining restriction
      and cold water swimming. Acupuncture was applied to "Baihui"(GV 20), "Guanyuan"
      (CV 4) and "Zusanli" (ST 36, bilate-ral) acupoints, once a day for two weeks. The
      ginsenoside group was gavage administrated with ginsenoside, once a day for two
      weeks. After 14 days, behavioural changes were observed, and the expression
      levels of T-bet/GATA-3 genes in plasma were detected by RT-PCR. RESULTS: Compared
      with the blank control group, the time for immobility of forced suspensory test
      was signi-ficantly longer (P<0.05) and the time for exhaustive swimming was
      significantly shortened (P<0.05) in the CFS model group. Compared with the model
      group, the two indexes above-mentioned were reversed (P<0.05) both in the
      acupuncture group and the ginsenoside group, and the effects in the acupuncture
      group were more significant than those in the ginsenoside group (P<0.05).
      Compared with the blank control group, the expression level of T-cell
      transcription factor T-bet gene in plasma was higher in the CFS model group
      (P<0.05), companied with lower GATA-3 gene expression (P<0.05). The ratio of T
      bet/GATA-3 was higher in the model group than in the blank control group(P<0.05).
      Compared with the CFS model group, all the indexes above-mentioned were reversed
      (P<0.05) in the two treatment groups. Acupuncture group showed a better effect on
      reducing T-bet gene expression than the ginsenoside group (P<0.05). CONCLUSIONS:
      Acupuncture can decrease the expression level of T-bet gene while increase the
      expression of GATA-3 gene, which may be associated with its role in treating CFS.

PMID- 29071983
TI  - [A Preliminary Study on Effect of Transcutaneous Electrical Acupoint Stimulation
      for Children with Autism].
AB  - OBJECTIVE: To investigate the clinical efficacy of transcutaneous electrical
      acupoint stimulation (TEAS) in treating children with autism spectrum disorders.
      METHODS: Forty-one autistic children receiving rehabilitation training were
      randomized into TEAS (n=21) and control (n=20) groups. The control group only
      received rehabilitation training. The TEAS group received both rehabilitation
      training and TEAS treatment[2 Hz/15 Hz alternating frequencies through two pairs
      of skin electrodes placed at Hegu (LI 4)-Neiguan (PC 6) on unilateral side, and
      Zusanli (ST 36)-Sanyinjiao (SP 6) on the contralateral side]. The treatment was
      given 30 min per day for 12 weeks. The outcome assessment was quantified with a
      series of rating scales including Autism Behavior Checklist (ABC), Childhood
      Autism Rating Scale (CARS) and Parent Symptom Questionnaire (PSQ). RESULTS: (1)
      The TEAS group showed more significant improvement than the control group in ABC
      (P<0.01). 38.1% effective rate (8/21) was observed in the TEAS group compared to
      5.0% (1/20) in the control group (P<0.05). The CARS scores of both groups were
      reduced (P<0.0001) after treatment. The TEAS group showed significantly lower
      score compared to the control group (P<0.0001). (2)There was a distinctly reduced
      PSQ score in both TEAS and control groups (P<0.001) after treatment.(3)TEAS
      intervention showed better effect in children under 6 years old with moderate or
      severe autistic symptoms. CONCLUSIONS: TEAS intervention can significantly
      improve the autistic symptoms.

PMID- 29071985
TI  - [Effect of Acupuncture at Phenomaxillary Ganglia and Local Points for Allergic
      Rhinitis].
AB  - OBJECTIVE: To observe the efficacy of acupuncture at phenomaxillary ganglia and
      local acupoints for symptoms induced by allergic rhinitis (AR). METHODS: Fifty AR
      patients were randomly divided into treatment group (n=26) and control group
      (n=24). Patients of the treatment group were treated by needling in
      phenomaxillary ganglia, and then at Yingxiang (LI 20,bilateral) and Yintang (EX
      HN 3) for 20 min,twice per week with a total treatment period of 4 weeks.
      Needling in left and right phenomaxillary ganglia was alternately performed.
      Patients in the control group were treated with oral loratadine tablets for 4
      weeks. The clinical efficacy, AR symptoms score and Visual Analogue Scale (VAS)
      score were assessed before and after the treatment. RESULTS: The total clinical
      efficacy of the treatment and control groups was 76.91% (20/26) and 54.17%
      (13/24), respectively, the therapeutic effect of the treatment group was
      obviously superior to that of the control group (P<0.05). In the treatment group,
      both symptoms and VAS scores were lower after treatment compared with those
      before treatment(P<0.01)and those in the control group (P<0.05). CONCLUSIONS:
      Needling in phenomaxillary ganglia and local points is effective in relieving AR
      induced symptoms.

PMID- 29071984
TI  - [Observation on the Efficacy of Electroacupuncture for Functional Constipation].
AB  - OBJECTIVE: To investigate the therapeutic rule of electroacupuncture (EA) in
      treating functional constipation. METHODS: Eighty-eight patients with severe
      chronic functional constipation were randomized divided into EA (n=45) and sham
      EA (n=43) groups. Patients in the EA group were treated with EA at bilateral
      Tianshu (ST 25), Fujie (SP 14), Shangjuxu (ST 37), and those in the sham-EA group
      were received superficial acupuncture at 1 cun lateral to the identical acupoints
      without electrical current delivery. The number of patients with complete
      spontaneous bowel movements (CSBM) was weekly compared between the EA and sham-EA
      groups at baseline week, during 8 weeks' treatment, as well as the follow-up 4th,
      8th and 12th weeks after treatment. The Bristol Stool Chart (BSC) and defecation
      difficulty scores were also weekly compared from baseline until 8 weeks. RESULTS:
      The CSBM showed significant differences from 3 to 8 weeks and at 4th, 8th and
      12th weeks post-treatment (P<0.05), but not within the first two weeks between
      the EA and sham-EA groups. The number of patients who had more than 3 times of
      CSBM per week was increased in the EA group(P<0.05). The therapeutic effect of EA
      group was superior to that of the sham-EA group in improving BSC over the 4th and
      5th weeks (P<0.05). The defecation difficulty score was improved in the EA group
      than in the sham-EA group since the 4th week (P<0.05). CONCLUSIONS: EA shows
      therapeutic effect for functional constipation by improving CSBM and BSC.

PMID- 29071986
TI  - [Effect of Acupuncture Therapy in Combination with Nutrition Control on Body
      weight Reduction in Postpartum Obesity Subjects].
AB  - OBJECTIVE: To observe the clinical effect of acupuncture therapy in the treatment
      of postpartum obesity subjects. METHODS: A total of 71 postpartum obesity
      subjects were allocated to treatment group (n=35) and control group (n=36).
      Participants of the control group were asked to receive weekly nutrition
      consultation (body-weight management) for calorie intake control during 4 weeks'
      treatment, and those of the acupuncture group were treated by manual acupuncture
      stimulation of Zhongwan (CV 12), Zhongji(CV 3), Qihai(CV 6), Shuifen (CV 9), and
      Guanyuan (CV 4), bilateral Tianshu (ST 25), Guilai (ST 29), Shousanli (LI 10),
      Zusanli (ST 36), Fenglong (ST 40), and Yinlingquan (SP 9) in combination with
      nutrition consultation. The treatment was conducted once every other day,
      continuously for 4 weeks. The body weight(BW), body mass index (BMI), percent of
      body fat (PBF) and waist-to-hip ratio (WHR) were determined before and after the
      treatment. RESULTS: After the treatment, the BW, BMI, PBF and WHR in the
      acupuncture group, and the BW and WHR in the control group were significantly
      decreased (P<0.01, P<0.05), and the therapeutic effect of the acupuncture group
      was notably superior to that of the control group in reducing BW and WHR (P<0.05,
      P<0.01). CONCLUSIONS: Acupuncture therapy combined with nutritional calorie
      control has a positive role in relieving obesity in postpartum obesity
      participants.

PMID- 29071987
TI  - [Clinical Research on Double-needle Winding and Pulling Combined with
      Electroacupuncture Therapy in Treating Scapulohumeral Periarthritis].
AB  - OBJECTIVE: To observe the efficacy of double-needle winding and pulling combined
      with electroacupuncture in treating scapulohumeral periarthritis. METHODS: Sixty
      cases with scapulohumeral periarthritis were equally randomized into treatment
      group and control group (n=30 in each group). Jianliao (TE 14), Jianyu(LI 15),
      Naoshu(SI 10), Jianzhen(SI 9), Binao(LI 14), Quyuan(SI 13), Quchi(LI 11),
      Shousanli(LI 10) were selected in the two groups. In the treatment group,double
      needles were inserted respectively into TE 14,LI 15 and SI 10, twirling till
      sticking,then the needles were pulled for 3 times.The rest acupoints were
      manipulated routinely before electroacupuncture apparatus was connected. The
      control group received routine electroacupuncture treatment. Both groups were
      treated for 2 courses, which comprised of 6 days as a course and 1 day rest. VAS
      and Melle were scored and clinical efficacy was evaluated for both groups.
      RESULTS: VAS and Melle scores were lower after treatment than those before in
      both groups (P<0.001), and the scores in the treatment group were significantly
      lower than those in the control group (P<0.001). The before-and-after-treatment
      difference values of VAS and Melle scores in the treatment group were
      significantly higher than those of the control group (P<0.01). There were 8 cases
      cured, 17 observed markedly effective and 4 effective in the treatment group, the
      rate of cured and markedly effective was 83.3%, which was significantly higher
      (P<0.01) than that of the control group (50.0%), in which 0 cases cured, 15
      observed markedly effective, 13 effective. No significant difference was observed
      between the two groups in total effective rate (P>0.05). No adverse event
      occurred during the treatment. CONCLUSIONS: The therapy of double-needle winding
      and pulling combined with electroacupuncture has good efficacy in treating
      scapulohumeral periarthritis,which can relieve pain and improve the shoulder
      joint function, and it is superior to single electroacupuncture therapy.

PMID- 29071988
TI  - [Review on Modern Repair Mechanism of Moxibustion for Treating Inflammatory
      Damage of Rheumatoid Arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease. Persistent
      inflammation of the synovial membrane is the main characteristic pathological
      symptom. Moxibustion for treating RA has achieved significant clinical effect in
      recent years. A large number of experimental studies have also shown that
      moxibustion promoted the repair of inflammatory damage induced by RA. Based on
      summarizing 10 years related literatures, the authors analyzed the repair
      mechanisms of moxibustion for inflammatory damage in RA from central mechanisms
      including glucocorticoid receptor, melatonine, hypothalamic-pituitary-adrenal
      axis, and cholinergic nerve to peripheral mechanisms including local inflammatory
      mediators, cytokine, and inflammatory cell signaling pathway, so as to provide
      evidences and reference for further research.

PMID- 29071989
TI  - [Systematic Evaluation and Meta-analysis on Acupuncture for Peptic Ulcer].
AB  - OBJECTIVE: To systematically evaluate the clinical efficacy of acupuncture for
      peptic ulcer. METHODS: Randomized controlled trials of acupuncture for peptic
      ulcer were searched from China National Knowledge Infrastructure (CNKI), WanFang
      Database, Chinese Scientific and Technological Journals (VIP), China Biomedicine
      (CBM), PubMed and the Cochrane Library from the establishment time of databases
      to September, 2016. Data extraction and quality evaluation were implemented for
      the literature which met the inclusive criteria. The RevMan 5.3 software was used
      to make Meta-analysis. RESULTS: Sixteen papers including 1 570 patients of peptic
      ulcer were included. The results of Meta-analysis showed that there was no
      statistical significance between acupuncture and western medicine in the
      effective rate, the healing rate of ulcer area and the HP negative rate (all
      P>0.05); the recurrence rate of acupuncture was significantly lower than that of
      western medicine[RR=0.35, 95%CI (0.14, 0.84), P<0.05]. Acupuncture plus western
      medicine was significantly different from simple western medicine in the
      effective rate, the healing rate of ulcer area and the recurrence
      rate[RR=1.20,95% CI (1.04, 1.38), P=0.01; RR=1.29, 95% CI (1.06, 1.58),
      P=0.01;RR=0.27, 95% CI (0.16, 0.45), P<0.00001]. The analysis of evidence grade
      (GRADE) pre-sented that the healing rate of ulcer area and the HP negative rate
      of acupuncture were "low grade", and others were "extremely low grade".
      CONCLUSIONS: Acupuncture combined with western medicine has some advantages for
      peptic ulcer compared with the conventional western medicine, which needs further
      confirmation due to the lower evidence grade. Larger samples, randomized
      controlled trials with high quality are highly recommended.

PMID- 29071990
TI  - [Effect of Electroacupuncture Intervention on Expression of Synaptic Plasticity
      related Molecules in Amygdala in Chronic Pain-negative Affection Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of
      synaptic plasticity-related glutamate N-methyl-D-aspartate (NMDA) receptor
      subunit NR 1, gamma-aminobutyric acid (GABA) receptor subunits (Abeta 2, B 1),
      etc. in the amygdala in chronic neuropathic pain negative affection (CNPPNA)
      rats, so as to reveal its mechanism underlying pain relief. METHODS: Male Wistar
      rats were randomized into normal control, CNPPNA model, EA, and anesthesia+EA
      (AEA)groups (n=14 in each group, 8 for quantitative RT-PCR and 6 for
      immunofluorescence staining). The CNPPNA model was established by ligation of the
      left sciatic nerve and repeated electrical stimulation of the hindpaw plantar
      skin in the pain-paired compartment. EA was applied to bilateral "Zusanli"(ST
      36)and "Yanglingquan"(GB 34)for 30 min, once daily for 7 days.Thermal pain
      threshold (paw withdrawal latency, PWL)of the bilateral paws was measured by
      using a Tail-Flick Unit. The conditioned place aversion (CPA) was determined by
      using a CPA-paired compartment. The expression levels of GABAAbeta 2, GABAB 1,
      NMDA receptor subunit NR 1, postsynaptic density-95 protein(PSD-95), Piccolo
      genes in the right amygdala area were determined using quantitative RT-PCR, and
      the immunoactivity of metabotropic glutamate receptor subunit 1 (mGluR 1) and
      GABAB 2 in the basolateral amygdala (BLA) nucleus was detected using
      immunofluorescence staining. RESULTS: After modeling, PWL difference (PWLD)
      values of the model group were significantly increased (P<0.001),and the time
      spent in the CPA-paired compartment was considerably decreased compared with the
      control group (P<0.001).After EA intervention for 3 and 7 days, the PWLD levels
      of both EA and AEA groups were apparently decreased(P<0.05),and the time spent in
      the CPA-paired compartment was apparently increased in the EA and AEA
      groups(P<0.05),suggesting a pain relief and an improvement of the negative
      affection after EA intervention. Additionally, following EA, the apparently
      decreased expression levels of GABAAbeta 2,GABAB 1,PSD-95,Piccolo genes and the
      reduced numbers of GABAB 2 positive cells and NMDA-NR 1 mRNA as well as mGluR 1
      positive fiber numbers were remarkably increased in the EA group (P<0.05,
      P<0.001).The expression levels of Piccolo gene, GABAB 2 and mGluR 1 positive
      cells/fiber numbers were apparently lower in the AEA group than in the EA group
      (P<0.001). No significant differences were found between the EA and AEA groups in
      the PWLD, time spent in the CPA-paired compartment, and the expression levels of
      NMDA-NR 1, GABAAbeta 2, GABAB 1 and PSD-95 genes (P>0.05). CONCLUSIONS: Repeated
      EA stimulation of ST 36-GB 34 has a role in relieving both sensory and affection
      dimensions of chronic pain in CNPPNA rats, which Feb be respectively related to
      its effects in up-regulating the expression of GABAAbeta 2, GABAB 1, NMDA-NR 1,
      PSD-95 and Piccolo genes, and in promoting the expression of mGluR 1 and GABAB 2
      proteins and Piccolo gene in the amygdala.

PMID- 29071991
TI  - [Effect of Electroacupuncture on Expression of Apelin-APJ System of Cerebral
      Vascular Endothelial Cell in Rats with Cerebral Infarction].
AB  - OBJECTIVE: To observe the regulation of APJ and its ligand Apelin on the
      angiogenesis pathway after cerebral infarction and the intervention effect of
      acupuncture. METHODS: Wistar rats were randomly divided into model group(n=90),
      electroacupuncture(EA) group(n=90), sham operation group(n=90) and control
      group(n=10). The first three groups were further divided into 1,3,6,9,12,24 h and
      3,7, 12 d subgroups(n=10 in each subgroup). The cerebral infarction model was
      established by middle cerebral artery occlusion (MCAO). EA(15 Hz, 2 mA) was
      applied to "Shuigou" (GV 26) for 20 min in the EA group. The 1, 3, 6, 9, 12, 24 h
      subgroups were treated immediately after modeling, the 3, 7, 9 d subgroups were
      treated once daily for 3, 7 or 9 days. Real-time fluorescent quantitative (RT
      PCR) and Western blot were applied to detect the changes of Apelin and APJ in
      cerebrovascular endothelial cells, respectively. RESULTS: Compared with the
      control group, the expression of Apelin-APJ mRNA was decreased in the model
      group(12 h, 12 d, P<0.05, P<0.01); After EA, the Apelin mRNA expression was
      increased in the 12 h and 7 d subgroups (P<0.01), while the APJ mRNA expression
      was increased in the 6, 9, 12 h subgroups(P<0.05, P<0.01). Compared with the
      control group, the Apelin(1, 3, 6, 24 h and 3, 7, 12 d) and APJ(1, 3, 6, 9 h and
      3 d) protein expressions were decreased in the model group(P<0.01, P<0.05); After
      EA, the Apelin protein expression was increased in the 6, 24 h and 3, 7, 12 d
      subgroups (P<0.05, P<0.01), while the APJ protein expression was increased in the
      1, 9, 12, 24 h and 3, 7, 12 d subgroups (P<0.05, P<0.01). CONCLUSIONS: EA can up
      regulate the expression of Apelin-APJ mRNA and protein of cerebral vascular
      endothelial cell in MCAO rats which has an important role in the establishment of
      blood vessel regeneration and collateral circulation.

PMID- 29071992
TI  - [Effect of Electroacupuncture Stimulation at "Dazhui" (GV 14) and "Mingmen"(GV 4)
      on Cell Apoptosis of Spinal Cord and Expression of JNK Signaling Related Protein
      in Spinal Cord Injury Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation at
      "Dazhui" (GV 14) and "Mingmen" (GV 4) of the Governor Vessel at different time
      points on spinal cord neuronal apoptosis and the expression of c-Jun N-terminal
      kinases (JNK) protein in spinal cord injury (SCI) rats, so as to reveal its
      mechanism underlying improving SCI. METHODS: A total of 108 male SD rats were
      randomly divided into normal control, SCI model and EA groups which were further
      divided into 1, 3 and 7 d subgroups (12 rats/subgroup, 6 rats in each subgroup
      for TUNEL or Western blot, separately). SCI model was established by using the
      modified Allen's method. EA was applied to GV 14 and GV 4 for 20 min, once daily,
      for 1, 3 and 7 days, respectively. Basso-Beattie-Bresnahan (BBB) scale was
      adopted to assess the locomotor function of rats, the TUNEL method was used to
      examine neuronal apoptosis of injuried spinal cord, and the expression of
      phosphorylated (p)-c-Jun protein of T9-T11 spinal cord was detected by using
      Western blot. RESULTS: After modeling, the BBB scores of SCI rats on day 1, 3 and
      7 were signi-ficantly decreased (P<0.01), while the numbers of apoptotic neuronal
      cells and the expression levels of p-c-Jun protein in the spinal cord were
      considerably increased at the 3 time-points in the model group (P<0.01, P<0.05).
      Following EA intervention, the decreased BBB scores on day 3 and 7, and the
      increased numbers of apoptotic neuronal cells on day 1, 3 and 7 and the up
      regulated expression levels of p-c-Jun protein on day 3 and 7 were obviously
      suppressed (P<0.05, P<0.01). CONCLUSIONS: EA intervention can improve the
      locomotor function of SCI rats, which Feb be related to its effects in reducing
      neuronal apoptosis and down-regulating p-c-Jun protein in the injuried spinal
      cord.

PMID- 29071993
TI  - [Influence of Electroacupuncture Stimulation with Different Intensities and
      Therapeutic Intervals on Learning-memory Ability and Expression of Abeta 1-40 and
      Arginine Vasopressin Genes in the Hippocampal CA 1 Region in VD Rats].
AB  - OBJECTIVE: To observe the influence of electroacupuncture (EA) stimulation with
      different electrical current intensities and therapeutic intervals on learning
      memory ability and expression of beta-amyloid peptide Abeta 1-40 and arginine
      vasopressin (AVP) genes in the hippocampal CA 1 region in vascular dementia (VD)
      rats, so as to provide evidence for treatment of VD. METHODS: A total of 48 male
      SD rats were randomly divided into sham, model, 0.5 mA-5 d-EA, 1.5 mA-5 d-EA, 0.5
      mA-1 d-EA and 1.5 mA-1 d-EA groups (n=8 in each group). The VD model was
      established using modified 4-vessels occlusion method. EA (alternative 2 Hz/15
      Hz, 0.5 mA, 1.5 mA) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) for 30
      min, once a day (1 d) or once every 5 d for 10 times. The learning-memory ability
      was detected using Morris water maze tests (place navigation task and spatial
      probe trials), and the expression of Abeta 1-40 and AVP genes in hippocampal CA 1
      region was determined using real time-PCR. RESULTS: In comparison with the sham
      group, the average escape latency of place navigation task, and the duration for
      crossing the target-platform for the 1st time (spatial navigation task) were
      significantly increased (P<0.05), and the times to cross the target-platform
      within 2 min (spatial probe trials) were significantly decreased in the model
      group (P<0.05), suggesting a reduction of learning-memory ability. The expression
      level of Abeta 1-40 mRNA was remarkably increased (P<0.05), and that of AVP mRNA
      notably decreased in the model group (P<0.05). Following EA intervention, the
      increased escape latency and the duration of crossing the target-platform for the
      1st time and the increased Abeta 1-40 mRNA expression, and the decreased target
      platform crossing times within 2 min as well the down-regulated AVP mRNA
      expression level were reversed in the 4 EA groups compared with the model group
      (P<0.05). The therapeutic effects of higher stimulating intensity (1.5 mA-1 d-EA
      and 1.5 mA-5 d-EA) were markedly superior to those of lower intensity (0.5 mA-1 d
      EA and 0.5 mA-5 d-EA), and the effects of higher frequency of EA intervention
      (0.5 mA-5 d-EA and 1.5 mA-5 d-EA) were obviously superior to those of lower
      frequency of EA (0.5 mA-1 d-EA and 1.5 mA-1 d-EA) in suppressing the increased 3
      indexes and the decreased 2 indexes mentioned above (P<0.05). CONCLUSIONS: EA can
      improve the learning-memory ability of VD rats, which Feb be related to its
      effects in inhibiting the expression of Abeta 1-40 mRNA and up-regulating the
      expression of AVP mRNA in hippocampal CA 1 region; and the therapeutic effects of
      higher stimulating intensity and higher intervention frequency are obviously
      better than those of lower stimulating intensity and lower therapeutic frequency.

PMID- 29071994
TI  - [Effect of "Jiaji"(EX-B 2)-electroacupuncture Preconditioning on Expression of
      Cytochrome P 450 Signaling Pathways in Myocardial Ischemia-reperfusion Rats].
AB  - OBJECTIVE: To investigate the effect of "Jiaji"(EX-B 2)-electroacupuncture(EA)
      preconditioning on the myocardium and expression of cytochrome P 450 signaling
      pathways of myocardial cells in myocardial ischemia-reperfusion injury(MI/RI)
      rats. METHODS: Sixty male Wistar rats were randomly divided into sham operation,
      model, Jiaji, Neiguan(PC 6), Yanglingquan(GB 34) and Quchi(LI 11) groups (n=10 in
      each group). MI/RI model was established by occlusion of the descen-ding anterior
      branch of the left coronary artery. EA preconditioning was respectively applied
      to EX-B 2, PC 6, GB 34 and LI 11 for 30 min, once daily for 7 days. The ECG-ST
      segment was detected before and after the modeling. The contents of serum
      creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) were detected by ELISA
      and microplate method separately. The expression levels of myocardial CYP 450
      related genes cyp 1 a 1, cyp 2 b 2, cyp 2 c 11, cyp 4 a 2 were detected by Real
      time PCR. RESULTS: Thirty minutes after ligation the changes of ECG-ST segment
      displacement of the Jiaji group and Neiguan group were signifi-cantly lower than
      that of the model group(P<0.01), and the change was significantly lower in the
      Neiguan group than in the model group(P<0.01) 30 minutes after reperfusion.
      Compared with the sham operation group, the activities of serum CK-MB and LDH
      were significantly increased in the model group(P<0.01). Compared with the model
      group, the activities of serum CK-MB and LDH were significantly decreased in the
      Jiaji, Neiguan and Yanglingquan groups (P<0.01). Compared with the Jiaji group,
      the activity of serum LDH was significantly increased in the Quchi group, while
      the activities of serum CK-MB were significantly increased in the Quchi and
      Yanglingquan groups (P<0.05). Compared with the sham operation group, the
      expression levels of myocardial cyp 1 a 1 and cyp 2 b 2 mRNAs were significantly
      higher in the model group(P<0.01), while the expression of cyp 2 c 11 mRNA was
      lower(P<0.01). Compared with the model group, the expression levels of cyp 1 a 1
      and cyp 4 a 2 mRNAs were lower in the Jiaji, Neiguan and Yanglingquan groups
      (P<0.01), while the expressions of cyp 2 b 2 and cyp 2 c 11 mRNAs were
      higher(P<0.01). Compared with the Jiaji group, the expression of cyp 1 a 1 mRNA
      was lower in the Neiguan group, while the expression of cyp 2 b 2 mRNA was
      higher(P<0.05). CONCLUSIONS: EA preconditioning at Jiaji(EX-B 2) can reduce serum
      myocardial enzymes of myocardial ischemia-reperfusion rats, lower the ST segment
      of electrocardiogram, up-regulate myocardial CYP 450 epoxygenase cyp 2 b 2 and
      cyp 2 c 11 mRNAs expression, down-regulate omega-hydroxylase cyp 1 a 1 and cyp 4
      a 2 mRNAs expression, thus play a role in myocardial protection.

PMID- 29071995
TI  - [Effects of Electroacupuncture and Moxibustion Pretreatment on Expressions of HSP
      27, HSP 70, HSP 90 at Different Time-points in Rabbits with Myocardial Ischemia
      reperfusion Injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) and moxibustion
      (Moxi) pretreatment on expression of myocardial heat shock protein (HSP) in acute
      myocardial ischemia-reperfusion injury (MIRI) rabbits. METHODS: A total of 72 New
      Zealand rabbits were randomly divided into 4 groups:sham operation, MIRI model,
      EA pretreatment and Moxi pretreatment (n=18 rabbits in each group) which were
      further divided into 0, 24 and 48 h (time-point) subgroups (n=6 in each). The
      MIRI model was established by occlusion of the anterior descending branch (ADB)
      of the left coronary artery for 40 min and reperfusion for 60 min. EA and Moxi
      stimulation was respectively applied to bilateral "Neiguan"(PC 6) for 20 min,
      once daily for 5 days before ADB occlusion. The expressions of myocardial HSP 27,
      HSP 70 and HSP 90 were detected by immunohistochemistry. The pathological and
      ultrastructural changes of left ventricular ischemia tissue were observed under
      light and transmission electronic microscope (TEM), respectively. RESULTS:
      Outcomes of H.E. staining and ultrastructure showed that MIRI-induced changes of
      disordered arrangement of cardiomyocytes, vague myocardial transverse striation,
      inflammatory infiltration, cardiac myofibre necrosis and fibrolysis (light
      microscope), and myofiber atrophy, vague and disorder in the arrangement of
      myofiber, myofilament necrosis, interstitial edema, mitochondrial swelling,
      microvessel expansion, etc. (TEM) were relatively milder in both EA and Moxi
      pretreatment groups (48 h). In comparison with the sham group, the expression
      levels of myocardial HSP 27, HSP 70 and HSP 90 had no significant changes after
      MIRI at the 3 time-points (P>0.05). In the pretreatment groups, the expression
      levels of HSP 27 at 24 and 48 h in both EA and Moxi groups, HSP 70 at 48 h in
      both groups, HSP 70 at 0 and 24 h in the Moxi group were significantly up
      regulated compared with the model group (P<0.05, P<0.01). No significant changes
      were found in the expression of HSP 90 at the 3 time-points in the EA and Moxi
      pretreatment groups (P>0.05). No significant differences were found between EA
      and Moxi in up-regulating expressions of myocardial HSP 27, HSP 70 and HSP 90
      proteins at the 3 time-points (P>0.05) except HSP 70 at 24 h (Moxi being stronger
      relative to EA, P<0.05). CONCLUSIONS: EA and Moxi pretreatment has a protective
      effect on ischemic myocardium in MIRI rabbits, which Feb be associated with their
      actions in up-regulating myocardial HSP 27 and HSP 70 expression.

PMID- 29071996
TI  - [Effect of Electroacupuncture on Adenosine Receptor Expression in White Adipose
      Tissue of Diet-induced Obese Mice].
AB  - OBJECTIVE: To investigate the effects of electroacupuncture (EA) on the
      expression of adenosine receptor (AR) in the white adipose tissue (WAT) of diet
      induced obese (DIO) mice, so as to reveal a peripheral mechanism of EA underlying
      improvement of body weight. METHODS: Forty three-week-old C 57 BL/6 male mice
      were divided into normal diet group (n=12) and high fat diet group (n=28)
      randomly, and fed by normal diet and high fat diet for 12 weeks, respectively. In
      the high fat diet group, mice with body weight over 20% heavier than that of the
      normal diet group were considered as obese mice. The normal diet mice and the
      obese mice were divided into normal group (CD, n=5) and normal plus EA group
      (CD+EA, n=7), or obese group (HFD, n=6) and obese plus EA group (HFD+EA, n=12).
      The CD+EA group and the HFD+EA group were treated with EA at "Zusanli"(ST 36) and
      "Neiting"(ST 44, 2 Hz/15 Hz, 0.6-1.0 mA) for 20 min, 6 times a week for 4 weeks.
      Body weight, ratio of WAT/body weight were calculated, qPCR and Western blot were
      applied to detect mRNA and protein levels of adenosine receptors in the
      epididymal adipose tissue (Epi-WAT), respectively. RESULTS: Compared with the
      normal diet group, high fat diet significantly increased body weight in C 57 BL/6
      mice after feeding for 12 weeks (P<0.01); 18 out of 28 mice in the high fat diet
      group were classified as obesity. After treatment, the body weight and the ratio
      of Epi-WAT/body weight of the HFD group were increased than those in the CD group
      (P<0.05), the change of body weight in the HFD group was bigger than that in the
      CD group (P<0.01). Compared with the HFD group, the body weight and the ratio of
      Epi-WAT/body weight of the HFD+EA group were decreased after EA (P<0.05), the
      change of body weight was also significantly increased (P<0.01). No significant
      differences were found among the four groups in the expression level of A1R mRNA
      (P>0.05). The expression of A3R mRNA in the HFD group was lower than that in the
      CD group (P<0.01), while the expressions of A2A R and A2BR proteins were
      decreased in the HFD group than in the CD group (P<0.01). In comparison with the
      HFD group, the expression levels of A2AR and A2BR mRNAs and proteins were
      significantly up-regulated in the HFD+EA group, respectively (P<0.05, P<0.01).
      CONCLUSIONS: EA intervention is able to reduce the body weight of DIO mice, which
      Feb be associated with its effects in regulating the expression of A2AR and A2BR
      in WAT, suggesting a new mechanism of EA in accelerating peripheral WAT
      metabolism.

PMID- 29071997
TI  - [Effect of Electroacupuncture on Hypothalamus-Pituitary-Ovary (HPO) Axis in Rats
      with Peri-menopausal Depression].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on the hormones
      derived from the hypothalamus-pituitary-ovary (HPO) axis, so as to explore the
      neuroendocrine mechanism induced by EA on rats with perimenopausal depression
      disorder. METHODS: Sixty female sprague-dawley rats were randomly divided into
      blank control group, model group, sham-operation (sham) group, clomipramine
      group, and electroacupuncture (EA) group, with 12 rats in each group.
      Perimenopausal depression model was established by bilateral ovariectomy combined
      with chronic unpredictable stimulation.The EA group received continuous treatment
      at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) once a day for 28
      days. Estrous cycle and sucrose preference test were monitored, and serum
      estradiol (E2), luteinizing hormone (LH), gonadotropin releasing hormone (GnRH),
      and beta-endorphin (beta-EP) were detected by ELISA. RESULTS: Compared to the
      blank control group, sugar water consumpution rates decreased in the model group
      and sham group (P<0.05). Compared to the blank group and sham group, the serum LH
      and GnRH levels increased (P<0.05), companied with lower serum E2 and beta-EP
      levels in the model group (P<0.05). Compared to the model group, sugar water
      consumpution rates increased in the clomipramine group and EA group (P<0.05),
      both were companied with decreased serum LH and GnRH levels (P<0.05), and higher
      serum E2 and beta-EP levels (P<0.05). CONCLUSIONS: Electroacupuncture can relieve
      the symptoms of rat with perimenopausal depression by regulating the hormone
      secretion in HPO axis.

PMID- 29071999
TI  - [Effect of Electroacupuncture and Manual Acupuncture on Colonic Inflammatory
      Injury, Cytokine Levels and Cell Apoptosis in Ulcerative Colitis Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) and manual
      acupuncture interventions on colonic inflammatory injury, cytokine level and cell
      apoptosis in ulcerative colitis (UC)rats, so as to reveal its mechanisms
      underlying improvement of UC. METHODS: A total of 32 SD rats were randomized into
      control, model, EA and manual acupuncture groups (8 rats/group). The UC model was
      established by intrarectally administration of 5% trinitro-benzene-sulfonic acid
      (TNBS)+ dehydrated alcohol. Both "Quchi" (LI 11) and "Zusanli" (ST 36) were
      punctured with filiform needles for 20 min in the manual acupuncture group or
      stimulated with EA (8 Hz/25 Hz, 2-4 mA, and duration of 20 min) in the EA group.
      The treatment was conducted once daily for consecutive 6 days. Changes of body
      weight and pathological state of colitis were observed. The contents of pro
      inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6), anti-inflammatory cytokine
      (IL-10), homocysteine (Hcy) and myeloperoxidase (MPO, two oxygen free radicals
      associated substances) in the colon tissues were detected by ELISA, and the
      protein expression levels of Bcl-2,Bax,phosphorylated (p)-inhibitor of nuclear
      factor kappaB kinase alpha(IkappaBalpha) and p-p 65 (a subunit of nuclear factor)
      of colonic tissues were detected by Western blot, separately. RESULTS: Compared
      with the control group, the body weight was decreased and the state of the
      swelling and hemorrhage of the colon got worsened in the model group, while the
      state of the swelling and hemorrhage of the colon was better in both EA and
      manual acupuncture groups, and the body weight was clearly increased from day 4
      on in both treatment groups. The concentrations of colonic TNF-alpha, IL-1 beta,
      IL-6, IL-10, MPO and Hcy were all significantly higher in the model group than in
      the control group (P<0.01), but those of colonic TNF-alpha, IL-1 beta, IL-6 in
      both EA and manual acupuncture groups, those of MPO and Hcy in the EA group were
      significantly down-regulated following the intervention (P<0.05, P<0.01), and
      that of IL-10 was notably further increased in the manual acupuncture group
      (P<0.05). In addition, modeling-induced remarkable down-regulation of colonic Bcl
      2/Bax, and marked up-regulation of expression of IkappaBalpha and p-p 65 proteins
      were significantly suppressed in both EA and manual acupuncture groups (P<0.01).
      CONCLUSIONS: Both EA and manual acupuncture interventions Feb alleviate the
      colonic lesions in UC rats, which Feb be related to their functions in regulating
      levels of pro-inflammatory and anti-inflammatory cytokines, in balancing the
      expression of apoptosis-related protein and anti-apoptosis-related protein and in
      down-regulating the expression of the key nuclear transcription factors in the
      colonic tissue.

PMID- 29071998
TI  - [Effects of Different Acupuncture and Moxibustion Methods on Plasma NO, NOS and
      VIP Contents and the Expression of Colonic VIP Protein in Functional Constipation
      Rats].
AB  - OBJECTIVE: To compare the effects of filiform needling, electroacupuncture, and
      moxibustion on functional constipation in rats, and to explore the possible
      mechanism of these three different methods. METHODS: Male SD rats were randomly
      divided into blank control group (n=8), model group (n=11), medication group
      (n=8), filiform needling group (n=11), electroacupuncture group (n=11), and
      moxibustion group (n=11). Functional constipation model was established by
      intragastric administration with the suspension of loperamide hydrochloride,
      daily for six days in a week. One hour after each gavage, the medication group
      was treated with cisapride suspension, while the other three groups were treated
      with filiform needling, electroacupuncture, and moxibustion, respectively, at
      "Tianshu"(ST 25), "Shangjuxu" (ST 37) acupoints. The first defecation time was
      recorded. NO, NOS and VIP (vasoactive intestinal peptide) levels in plasma were
      detected by ELISA. Immuohistochemical and Western blot methods were applied to
      test VIP expression in the colonic tissue. RESULTS: Compared with the blank
      control group, the first defecation time was prolonged, and the NO, NOS and VIP
      contents in plasma were increased in the model group (P<0.05, P<0.01),
      accompanied with increased score of VIP in the smooth muscle of colonic
      wall(P<0.05)and elevated VIP expression in colonic tissue(P<0.01). Compared with
      the model group, the first defecation time was shortened in the medication,
      filiform needling, electroacupuncture, and moxibustion groups(P<0.05), while
      decreased NO, NOS and VIP contents in plasma (P<0.01,P<0.05), decreased score of
      VIP in the smooth muscle of colonic wall(P<0.05), and lower expression level of
      VIP in colonic tissue(P<0.01)were observed in the four treatment groups. In
      contrast, the plasma VIP content in the electroacupuncture group was lower than
      that in the medication group (P<0.01), while colonic VIP expression decreased in
      the moxibustion group(P<0.01). The NO, NOS and VIP contents in plasma and score
      of VIP in the smooth muscle of colonic wall in the electroacupuncture group were
      lower than those in the filiform needling group and the moxibustion group(P<0.01,
      P<0.05), but the colonic VIP expression in the moxibustion group was lower than
      that in the filiform needling group(P<0.05)and electroacupuncture group(P<0.01).
      CONCLUSIONS: All the three different kinds of acupuncture and moxibustion methods
      have positively regulatory effect on functional constipation; electroacupuncture
      is the best for the regulation of plasma NO, NOS and VIP contents, while
      moxibustion is the best for the regulation of VIP expression in colonic tissue.

PMID- 29072000
TI  - [Effect of Manual Acupuncture Stimulation of Single Acupoint or Acupoints
      Combination on Intestinal Movement in Slow Transit Constipation Mice].
AB  - OBJECTIVE: To observe the effect of acupuncture stimulation of different
      acupoints or acupoint groups on intestinal locomotor in slow transit constipation
      (STC) mice, so as to provide experimental evidence for demonstrating the synergic
      function of acupoint combination. METHODS: A total of 190 Kunming mice were
      randomized into 19 groups:normal control, model, uni-"Quchi" (LI 11), uni
      "Shangjuxu" (ST 37), uni-"Tianshu"(ST 25), and uni-"Dachangshu"(BL 25) groups,
      for analyzing the effect of single acupoint; normal control, model, uni-ST 25+uni
      BL 25, uni-LI 11+uni-ST 37, bi-ST 25, bi-BL 25, bi-LI 11, and bi-ST 37 groups,
      for comparing the effect between single acupoint and two acupoints combination;
      normal control, model, bi-ST 25+bi-BL 25, bi-LI 11+bi-ST 37, and uni-LI 11+uni-ST
      37+uni-ST 25 +uni-BL 25 groups, for comparing the effect between four acupoints
      and two acupoints combinations (10 mice/group). The STC model was established by
      intragastric administration of compound diphenoxylate suspension (1 mg/100 g),
      once daily for 2 days. Manual acupuncture needle stimulation (200 twirling
      times/min for 1 min) was applied to the abovementioned unilateral or bilateral
      acupoints twice daily for 7 times. The first defecation time, the defecation
      grain number in 12 h and the intestinal propulsion rate were determined using
      activated carbon gavage. RESULTS: Compared with the normal group, the first
      defecation time was significantly increased in the STC model group (P<0.01),
      while the 12 h defecation grain number and the intestinal propulsion rate were
      considerably decreased in the model group (P<0.01). After manual acupuncture
      intervention, the first defecation time was notably shortened in the uni-LI 11,
      uni-ST 37, uni-ST 25, uni-BL 25, bi-ST 25, bi-BL 25, bi-LI 11, bi-ST 37, uni-ST
      25+uni-BL 25, uni-LI 11+uni-ST 37, bi-ST 25+bi-BL 25, bi-LI 11+bi-ST 37 and the
      uni-ST 25+uni-BL 25+uni-LI 11+uni-ST 37 groups compared with the model group
      (P<0.05), while both the 12 h defecation grain number and intestinal propulsion
      rate were considerably increased in the abovementioned 13 acupuncture groups
      (P<0.05, P<0.01). The effects of uni-ST 25+uni-BL 25 and uni-LI 11+uni-ST 37 were
      significantly superior to those of bi-ST 25, bi-BL 25, bi-LI 11 and bi-ST 37
      groups, and those of the uni-ST 25+uni-BL 25+uni-LI 11+uni-ST 37 group were
      markedly superior to those of bi-ST 25+bi-BL 25 and bi-LI 11+bi-ST 37 groups in
      shortening the first defecation time and in increasing the 12 h defecation grain
      number and intestinal propulsion rate (P<0.05). CONCLUSIONS: Acupuncture
      stimulation of LI 11, ST 37, ST 25 and BL 25 can improve constipation in STC
      mice, and the effect of two acupoints combination is significantly superior to
      that of the corresponding bilateral single acupoint, and that of the 4 unilateral
      single acupoint combination is obviously superior to that of two bilateral
      acupoints combination, suggesting a synergistic action of acupuncture
      stimulation.

PMID- 29072001
TI  - [Randomized Controlled Clinical Trials of Eye-acupuncture Therapy for Patients
      with Post-stroke Insomnia].
AB  - OBJECTIVE: To observe the therapeutic effect of eye-acupuncture therapy for post
      stroke insomnia. METHODS: Sixty patients (45-70 years in age) with post-stroke
      insomnia were randomized into eye-acupuncture group and routine acupuncture (body
      acupuncture) group (30 cases in each). Patients of the eye-acupuncture group were
      treated by acupuncture stimulation of bilateral Shangjiao (Upper-energizer) and
      Xin (Heart) regions and those of the routine acupuncture group treated by
      acupuncture stimulation of Baihui (GV 20), Sishencong (EX-HN 1), Anmian (EX-HN
      16), etc. After Deqi, the filiform needles were retained for 20 min, and the
      treatment in both groups was conducted once a day, with 15 days being one
      therapeutic course and 2 courses altogether. The Pittsburgh Sleep Quality Index
      (PSQI) including the subjective sleep quality, sleep latency, sleep duration,
      habitual sleep efficiency, sleep disturbances, daytime dysfunction, and total
      PSQI score was used to evaluate the overall sleep quality. The clinical efficacy
      was assessed according to the "Guiding Principles of Clinical Trials for New
      Drugs of Traditional Chinese Medicine" formulated by Chinese Ministry of Health.
      RESULTS: Following the treatment, of the two 30 cases in the eye-and routine
      acupuncture groups, 21 and 9 experienced a marked improvement in their symptoms,
      8 and 17 were effective, and 1 and 4 invalid, with the effective rate being 96.7%
      and 86.7%, respectively. The PSQI scores of the subjective sleep quality, sleep
      latency, sleep duration, habitual sleep efficiency, sleep disturbances, daytime
      dysfunction, and the total PSQI score were all significantly decreased in
      comparison with pre-treatment in each group (P<0.01). The therapeutic effect of
      the eye-acupuncture was markedly superior to those of routine acupuncture in
      reducing sleep latency, sleep disturbances and daytime dysfunction (P<0.05), but
      without significant differences between the two groups in the effective rate,
      sleep quality, sleep duration, sleep efficiency and total PSQI score (P>0.05).
      CONCLUSIONS: Both eye-acupuncture and routine acupunture are effective in the
      treatment of post-stroke insomnia, and the eye-acupuncture is better than routine
      acupuncture in reducing sleep latency, improving sleep disturbances and daytime
      dysfunction.

PMID- 29072002
TI  - [Clinical Trials for Treatment of Acute Lumbar Sprain by Acupuncture Stimulation
      of "Yaotong" and Local Ashi-points in Combination with Patients' Lumbar
      Movement].
AB  - OBJECTIVE: To observe the clinical effect of acupuncture stimulation of "Yaotong"
      point (one acupoint of balance acupuncture therapy) and Ashi-points combined with
      patients' lumbar movement in the treatment of acute lumbar sprain. METHODS: Forty
      six acute lumbar sprain patients were randomized into treatment group (26 cases)
      and control group (20 cases) using a random number table. The patients of the
      treatment group were treated by acupuncture stimulation of "Yaotong"-point[above
      Yintang (EX-HN 3)] and local Ashi-points for 20 min, and were asked to move the
      waist simultaneously during acupuncture stimulation. The treatment was conducted
      once every other day, 3 times a week, one week in total. Those of the control
      group were treated by oral administration of loxoprofen sodium tablets (60 mg,
      twice a day, for one week). The pain severity of lumbago and motor function were
      assessed by using visual analogue scale(VAS) and present pain intensity(PPI)and
      lumbar range of motion(ROM) separately. RESULTS: Following the treatment, of the
      20 and 26 acute lumbar sprain patients in the control and treatment groups,
      6(30.0%)and 14(53.8%)were cured, 9 (45.0%) and 11 (42.4%) experienced an
      improvement in their symptoms, 5 (25.0%) and 1 (3.8%) was invalid, with the
      effective rates being 75.0% and 96.2%, respectively. Compared with pre-treatment,
      the ROM and VAS scores were significantly decreased in both the control and
      treatment groups post-treatment (P<0.01), and the therapeutic effects of the
      treatment group were obviously superior to those of the control group in the
      effective rate and in the improvement of lumbar motion function and in pain
      relief (P<0.05,P<0.01). CONCLUSIONS: Acupuncture treatment plus patients' lumbar
      movement is effective in reducing lumbar pain and improving lumbar motor function
      in the treatment of acute lumbar sprain.

PMID- 29072004
TI  - [Differences on Acupuncture Reinforcing and Reducing Theory Between Neijing and
      Nanjing].
AB  - Reinforcing and reducing manipulation is the elite of traditional acupuncture
      needling methods. Abundant records could be found in Neijing(The Yellow Emperor's
      Inner Canon) and Nanjing (The Classic on Medical Problems) at early times. In the
      present paper, the author collates and compares the recordation of reinforcing
      and reducing acupuncture manipulation in these two classics on the basis of the
      principle and connotation of the two manipulations and from three key factors as
      stimulus location,manipulation technique and needling time. Based on objective
      analysis of the original text,distinct differences were found in above three
      aspects. Therefore, the conclusion is that Neijing and Nanjing resemble different
      medical school of thoughts at an early phase of acupuncture theories.

PMID- 29072003
TI  - [Qi Runs Through Acupuncture Needle Stimulation and Pulse Diagnosis:Our
      Considerations About Connotations of Qi in Acupuncture-Diagnosis-Treatment
      Scriptures in Yellow Emperor's Inner Canon].
AB  - The ancient classic work Yellow Emperor's Inner Canon has abundant expositions
      about the relationship between the acupuncture needle manipulation and pulse
      diagnosis. However, the relevant imparting and inheritance situations are
      relatively weaker nowadays probably due to the rapid development of modern
      diagnosis-therapeutic techniques and some faults or careless omission in
      understanding classical medical works. Qi, a core concept of the abundant
      expositions in Inner Canon, has seldom been thoroughly interpreted about its
      connotations. For this reason, in the present paper, the authors make a careful
      explanation about the connotations of Qi in Inner Canon from 1) the concept of
      Qikou (a superficial window of the body reflecting the functional state of
      internal organs), 2) pulse conditions, 3) its relationship with meridian
      collateral diagnosis, and 4) the link between acupuncture needle stimulation and
      pulse diagnosis based on the scriptures and words description in combination with
      many scholars' doctrines, trying to explore its profound significance. In
      addition, the authors also expound its association with the effectiveness of
      distant treatment of acupuncture and the characteristics in relation to ancient
      medical scholars' thoughts.

PMID- 29072005
TI  - [New Trains of Thoughts About Acupuncture Analgesia-Acupuncture Analgesia Feb
      Involve Multi-dimensional Regulation of Pain].
AB  - With the development of pain study, researchers gradually recognized that pain is
      composed of three main dimensions, namely "sensory-discriminative" "affective
      motivational" and "cognitive-evaluative" which influence each other and are also
      independent from each other. Pain study has shifted away from focusing on the
      single mode of nociception to the multi-dimensional mode of sensory-affection
      cognition. It is held early in traditional Chinese medicine that "when there is a
      stoppage, there is a pain" and a worsening disease Feb induce depression, which
      has already shown a multi-dimensional recognition about pain. Acupuncture therapy
      has been considered to be an effective adjuvant approach for relieving pain. In
      the present paper, the authors introduced applicability of acupuncture analgesia
      by modulating the abovementioned multi-dimensions of pain from the following 4
      aspects:1) multi-dimensions of pain and related brain regions; 2) recognitions of
      traditional Chinese medicine about pain; 3) development of researches on
      acupuncture analgesia, including a) balancing activities of endogenous analgesic
      and algogenic substances, and triggering intracellular mitogen-activated protein
      kinase (MAPK) signaling to reduce algesia, b) improving psychological symptoms of
      patients with depression, anxiety, insomnia, etc., c) modulating functional
      activities of some common brain regions (as hippocampus, anterior cingutate,
      frontal lobe of cerebral cortex, etc.) sharing both pain information and learning
      memory processing. Hence, the authors hold that if the clinical study and
      application and experimental researches conducted on the underlying mechanisms of
      acupuncture analgesia extend towards the multi-dimensions of pain, a series of
      new concepts or thoughts will be brought out, thereby possibly opening a bright
      applicable prospect for acupuncture analgesia.

PMID- 29072006
TI  - [Rule of Clinical Application of Auricular Acupuncture Based on Data Mining].
AB  - OBJECTIVE: To explore the rule of clinical application of auricular acupuncture
      therapy by data mining in order to guide clinical practice. METHODS: The data
      base about single auricular acupuncture therapy for different clinical diseases
      was established by collection, sorting, screening, recording, collation, data
      extraction, statistic analysis on data samples from journals, academic theses
      dissertations published in near 60 years. The application rules of auricular
      therapy including its predominant diseases, stimulus modality, therapeutic
      effect, and angle of needling were summarized by data mining technique. RESULTS:
      Auricular acupuncture therapy has been widely and mostly used in the internal
      medicine department, accounting for 48.56%. Of stimulus modalities, auricular
      point paste and pressure is applied with the highest frequency, accounting for
      64%. The highest effective rate is found in the surgery department
      diseases(81.41%). Pressure is the most effective stimulus in the internal medi
      cine department, and bloodletting combined with paste and pressure in the surgery
      department, auricular point injection in the gynecology and pediatrics
      departments, bloodletting in the ophthalmology and otorhinolaryngology
      department, and auricular point incision in the dermatology department. Auricular
      point injection has remarkable effect. Bloodletting combined with paste and
      pressure has nearly the same effect as bloodletting in the same medical
      department except dematology department. Otherwise, angle of needling is rarely
      studied. CONCLUSIONS: Auricular therapy is widely used and has remarkable effect
      in treating diseases by using different stimulus modalities. Whereas the angle of
      needling is rarely studied and future investigation is needed.

PMID- 29072007
TI  - [Effects of Electroacupuncture on Activities of Satellite Glial Cells of Dorsal
      Root Ganglia in Rats with Neck Incision Pain].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Futu"(LI 18), etc. on activities of satellite glial cells (SGCs) in the dorsal
      root ganglia (DRG) in rats with neck-incision pain so as to explore its mechanism
      underlying reduction of post-surgical pain of thyroidectomy. METHODS: Male SD
      rats were randomly divided into control, model, EA-Futu (LI 18), EA-Hegu (LI 4)
      Neiguan (PC 6), and EA-Zusanli (ST 36)-Yanglingquan (GB 34) groups, with 20 rats
      in each group. The neck-incision pain model was established by making a
      longitudinal incision and repeated mechanical stimulation. In the EA-LI 18, EA-LI
      4-PC 6 and EA-ST 36-GB 34 groups, EA stimulation was administrated for 30 min,
      once a day,continuously for 3 days. The thermal pain threshold (PT) of the neck
      incision region was detected. The immunoactivity of glial fibrillary acidic
      protein (GFAP,a specific marker for SGCs) and connexin 43 (Cx 43) of DRGs (C 2-C
      6) was determined by fluorescent immunohistochemistry. The expression levels of
      GFAP, IL-1 beta, IL-6, and TNF-alpha mRNAs were determined by quantitative Real
      time PCR, and the contents of IL-1 beta,IL-6,TNF-alpha assayed by enzyme linked
      immunosorbent assay (ELISA) and the expression of Cx 43 protein was detected by
      Western blot. RESULTS: After EA intervention at LI 18 and LI 4-PC 6 (but not ST
      36-GB 34), neck incision-induced reduction of the thermal PT was obviously
      prolonged in comparison with the model group (P<0.05),suggesting a pain relief.
      The expression levels of GFAP, IL-1 beta, IL-6 and TNF-alpha mRNAs and Cx 43
      protein, and the contents of IL-1 beta, IL-6 and TNF-alpha in C 2-C 6 DRGs were
      all significantly up-regulated in the model group relevant to those of the
      control group (P<0.05). Following EA, modeling induced dramatic increase of
      expression of GFAP, IL-1 beta, IL-6 and TNF-alpha mRNAs and Cx 43 protein in both
      EA-LI 18 and EA-LI 4-PC 6 groups, and the contents of IL-1 beta and TNF-alpha in
      the EA-LI 18 group, IL-6 in the EA-LI 4-PC 6 group was considerably down
      regulated (P<0.05). In comparison with the model group, no significant changes
      were found in all the abovementioned indexes of EA-ST 36 -GB 34 group except the
      down-regulated IL-1 beta and TNF-alpha mRNAs, in the contents of IL-1 beta and
      TNF-alpha of the EA-LI 4-PC 6 group, and in the IL-6 content of the EA-LI 18
      group (P>0.05). CONCLUSIONS: EA stimulation of LI 18 and LI 4-PC 6 can
      significantly suppress pain reaction of neck incision in the rat, which is
      closely associated with its effects in down-regulating the activity of SGCs,
      decreasing the release of pro-inflammatory cytokines and in weakening the
      expression of Cx 43 in the cervical DRGs.

PMID- 29072009
TI  - [Effect of Acupuncture on Expression of Receptor Tyrosine Kinase c-kit in
      Interstitial Cells of Cajal, Carbon Monoxide and Heme Oxygenase in Colon Tissue
      After Colonic Anastomosis in Rats].
AB  - OBJECTIVE: To observe the effect of acupuncture on expression of receptor
      tyrosine kinase (RTK) c-kit in interstitial cells of Cajal (ICCs), carbon
      monoxide (CO) and heme oxygenase (HO) in colon tissue after colonic anastomosis,
      so as to explore the mechanism of acupuncture in improving gastrointestinal
      motility. METHODS: SD rats were randomly devided into control group, model group
      and acupuncture group. The model was established using colonic anastomosis. Each
      group was further devided into 3, 5, and 10 d (time-point) subgroups (n=10 in
      each). Acupuncture was applied to acupuncture group at bilateral "Zusanli" (ST
      36), "Sanyinjiao" (SP 6) and "Taichong" (LR 3) for 15 min, once daily after
      modeling. The first defecation time was recorded, and the intestinal propulsive
      rate was measured. The expression of c-kit in colon tissue was detected by
      immunohistochemistry. The content of CO, the activities of HO-1 and HO-2 in colon
      tissue were detected by biochemical method and ELISA, respectively. RESULTS:
      Compared to the control group, the intestinal propulsive rate and the expression
      level of c-kit in ICCs were decreased in the model group(P<0.05), the content of
      CO and the activity of HO-1 were increased in model 3 d and 5 d
      subgroups(P<0.05), the activity of HO-2 was increased in model 3 d
      subgroup(P<0.05), while the opposite results appeared in model 5 d and 10 d
      subgroups(P<0.05). Compared to the model group, the first defecation time was
      shortened (P<0.05), the intestinal propulsive rate and the expression level of c
      kit in ICCs were increased in the acupuncture group (P<0.05), the content of CO
      and the activity of HO-1 were decreased in acupuncture 3 d and 5 d
      subgroups(P<0.05), the activity of HO-2 was decreased in acupuncture 3 d
      subgroup(P<0.05), while the opposite result appeared in acupuncture 10 d
      subgroup(P<0.05). Compared to the 3 d subgroup, the intestinal propulsive rate
      and the expression level of c-kit in ICCs were increased, the content of CO, the
      activities of HO-1 and HO-2 were decreased in both model and acupuncture 5 d
      subgroups (P<0.05). In model 10 d subgroup, the intestinal propulsive rate and
      the expression level of c-kit in ICCs were increased, the content of CO and the
      activity of HO-1 were decreased in comparison with the model 5 d
      subgroup(P<0.05). CONCLUSIONS: Acupuncture can improve postoperative
      gastrointestinal motility by declining CO content and HO-1 and HO-2 activity in
      colon tissue, and promoting ICCs restoration.

PMID- 29072008
TI  - [Effect of "Nape Seven Needles" on Expression of Dll 4 and Hes 1 in Cervical
      Intervertebral Disc Degeneration Rats].
AB  - OBJECTIVE: To observe the effect of "Nape Seven Needles" on the expressions of
      Delta-like ligand 4 (Dll 4) and hairy and enhancer of split homolog 1(Hes 1) in
      cervical intervertebral disc degeneration(IVDD) rats, so as to explore its
      mechanism of deferring the degeneration of cervical intervertebral disc. METHODS:
      SD male rats were randomly divided into a normal group, a model group and a nape
      seven needles group (n=11 in each group). The IVDD model was established by
      static-dynamic imbalance method. "Nape Seven Needles" acupoints were bilateral
      "Fengchi" (GB 20), "Tianzhu" (BL 10), "Wangu" (GB 12) and "Fengfu" (GV 16). The
      rats in the nape seven needles group were treated for 4 weeks, once a day, with
      needles retained for 20 minutes. Tilted plane test was used to observe the angle
      changes. The morphology of cervical intervertebral disc was observed after H.E.
      stain. Dll 4 and Hes 1 mRNA and protein expression in intervertebral disc tissues
      were detected by real-time fluorescent quantitative PCR and Western blot,
      respectively. RESULTS: Compared with that in the normal group, the angle of
      tilted plane in the model group decreased (P<0.05); compared with that in the
      model group, the angle in the nape seven needles group increased (P<0.05). The
      structure of cervical intervertebral disc was normal and the fiber ring was
      arranged orderly in the normal group. The morphology of cervical intervertebral
      disc is irregular in the model group, and the number of nucleus pulposus cells
      decreased compared with that in the normal group. The structure of cervical
      intervertebral disc in the nape seven needles group was similar to that in the
      normal group. Compared with that in the normal group, the expression of Dll 4
      mRNA decreased in the model group (P<0.05). The expression of Dll 4 mRNA in the
      nape seven needles group was higher than that in the model group (P<0.05). The
      expression of Hes 1 mRNA in the model group was higher than that in the normal
      group (P<0.05). The protein expressions of Dll 4 and Hes 1 in the nape seven
      needles group were higher than those in the model group (P<0.05). CONCLUSIONS:
      Acupuncture at "Nape Seven Needles" acupoints can defer the degeneration of
      cervical intervertebral disc, which may be related to its regulation of Dll 4 and
      Hes 1 mRNA and protein expression in the intervertebral disc tissue.

PMID- 29072010
TI  - [Effects of Electroacupuncture on Apoptosis-related Protein Expression of
      Gastrocnemius Muscle Cells in Rats with Denervated Sciatic Nerve].
AB  - OBJECTIVE: To observe the anti-apoptosis effect of electroacupuncture (EA) on
      gastrocnemius muscle cells in rats with denervated sciatic nerve, so as to
      explore its possible mechanisms underlying delaying atrophy of skeletal muscle.
      METHODS: Sixty-three male Sprague-Dawley rats were randomly divided into sham
      operation group, model group, and EA group, and then further divided into 3
      subgroups in each group(n=7/subgroup). Gastrocnemius muscle atrophy model was
      established by transecting the sciatic nerve of rat. EA (5 Hz, 1.5 mA) was
      applied to "Zusanli" (ST 36) and "Chengshan" (BL 57) acupoints at the affected
      side for 10 min, once a day for 1, 2, 3 weeks, respectively. The gastrocnemius
      muscles were sampled on the 7th, 14th, 21th d after modeling, separately. The
      apoptotic cells were detected by TUNEL staining. Bcl-2, Bax, Cyt-C and Caspase-3
      protein expressions were determined by Western blot. RT-PCR was used to check
      Caspase-3 gene expression. RESULTS: Compared with the sham operation group, the
      cell apoptotic index in gastrocnemius was markedly higher, gastrocnemius Bcl-2
      protein expression was markedly down-regulated, and gastrocnemius Bax, Cyt-C and
      Caspase-3 protein expressions were considerably up-regulated in the model group
      at all time-points (P<0.05). Compared with the model group, the cell apoptotic
      indexes in gastrocnemius were significantly lower in the three EA subgroups
      (P<0.05). Bcl-2 protein expressions were markedly up-regulated while Bax, Cyt-C
      and Caspase-3 protein expressions were significantly down-regulated in the EA
      group 14, 21 days after modeling compared with the corresponding model subgroups
      (P<0.05). The changes of Caspase-3 mRNA expression levels of gastrocnemius in all
      groups were similar to those of Caspase-3 protein expressions. CONCLUSIONS:
      Electroacupuncture intervention can effectively increase Bcl-2 expression and
      decrease Bax, Cyt-C and Caspase-3 expression in gastrocnemius muscle, and
      consequently reduce the apoptosis of muscle cell, which may contribute to its
      effect in delaying the skeletal muscle atrophy of denervated sciatic nerve.

PMID- 29072011
TI  - [Effect of Electroacupunctrue Stimulation at "Fenglong"(ST 40) on Expression of
      SREBP-1 c in Non-alcoholic Fatty Liver Disease Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture(EA) stimulation at
      "Fenglong"(ST 40) on expression of sterol regulatory element binding protein-1
      c(SREBP-1 c) in non-alcoholic fatty liver disease(NAFLD) rats, so as to reveal
      its mechanism underlying improving NAFLD. METHODS: Male SD rats were randomly
      divided into normal diet group, high-fat diet group, ST 40 manual acupuncture
      (MA) group, ST 40 EA group and "Zusanli"(ST 36) EA group(n=12 in each group).
      Apart from the normal diet group, rats in other groups were fed with high-fat
      diet to replicate NAFLD model. ST 40 MA group was treated with filiform needling
      for 20 min, EA (4 Hz/20 Hz, 5 mA) was applied to bilateral acupoints of ST 40 and
      ST 36 respectively for 20 min in the ST 40 EA group and ST 36 EA group, once a
      day for 4 weeks. The pathological changes of hepatic tissue were observed by HE
      staining. The contents of serum free fatty acid (FFA), alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) were detected by colorimetry. The
      expression of SREBP-1 c mRNA and protein in the hepatic tissue were detected by
      reverse transcription-polymerase chain reaction(RT-PCR) and Western blot,
      respectively. RESULTS: HE staining showed that hepatocytes disorganized with
      diffuse bullous fat vacuolar changes in rats of the high-fat diet group, and
      small vesicle steatosis appeared in the ST 40 MA group. The liver cells arranged
      orderly and the steatosis decreased in the ST 40 EA group and ST 36 EA group. The
      contents of FFA, ALT, AST in serum and the expression levels of SREBP-1 c mRNA
      and protein in the hepatic tissue were significantly higher in the high-fat diet
      group than in the normal diet group(P<0.01), while significantly lower in the MA
      and EA groups than in the high-fat diet group(P<0.01). Furthermore, the effects
      of treatment in the ST 40 EA group were better than those in the ST 40 MA
      group(P<0.01, P<0.05). The FFA contents in serum and the expression levels of
      SREBP-1 c mRNA and protein were decreased in the ST 40 EA group in comparison
      with the ST 36 EA group(P<0.05). CONCLUSIONS: EA at ST 40 and ST 36 have a
      positive regulating effect on NAFLD rats, which may be related to down-regulating
      the expression of SREBP-1 c mRNA and protein in hepatic tissue, improving the
      endoplasmic reticulum stress and regulating lipid metabolic disorder, so as to
      relieve the inflammatory injury in hepatic tissue, and ST 40 works better.

PMID- 29072012
TI  - [Effect of Electroacupuncture Intervention on Gastrointestinal Motility and
      Expression of Insulin-like Growth Factor 1 and Its Receptor Proteins in Gastric
      Antrum in Diabetic Gastroparesis Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention of
      "Zusanli"(ST 36), etc. on gastrointestinal motility and levels of insulin-like
      growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1 R) proteins in the gastric
      antrum in diabetic gastroparesis (DGP) rats, so as to study its mechanism
      underlying improvement of DGP. METHODS: Fifty SD rats, half male and half female,
      were randomly allocated to control, model, EA acupoint, EA non-acupoint and
      medication (metoclopramide) groups (n=10 rats/group). The DGP model was induced
      by 2% streptozotocin (STZ, i.p.i.,55 mg/kg) and high fat-sugar forage for 8
      weeks. EA (10 Hz/50 Hz, 2 mA) was applied to "Zusanli"(ST 36), "Liangmen"(ST 21),
      "Sanyinjiao"(SP 6) and non-acupoints (about 5 mm lateral to ST 36, ST 21 and SP
      6, respectively) for 20 min, one daily for 15 days, and 1.7% metocloppramide (1
      mL/100 g) was given (gavage) to rats of the medication group, once daily for 15
      days. After the treatment, the rats' general conditions were scored, the blood
      glucose level was determined using a glucometer, and the gastrointestinal
      mobility was evaluated by measuring the gastric emptying rate (GER) and the
      intestinal propulsion rates (IPR) marked by oral-infused phenol red solution (50
      mg/dL). The immunoactivity levels of IGF-1 and IGF-1 R of gastric antrum tissue
      were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: After
      modeling, the symptom integrative score, the blood glucose, IGF-1 and IGF-1 R
      levels were significantly increased (P<0.01), and the GER and IPR were notably
      decreased relevant to the control group (P<0.01). After EA stimulation of ST 36,
      ST 21 and SP 6, the symptom score, blood glucose, and IGF-1 and IGF-1 R levels of
      the gastric antrum were significantly reduced, while the GER and IPR were
      considerably increased (P<0.05,P<0.01). Except the GER and IPR were considerably
      increased in the medication group(P<0.05,P<0.01), no significant changes were
      found in the symptom integrative score, the blood glucose, IGF-1 and IGF-1 R
      levels in both EA non-acupoint and medication groups relevant to the model group
      (P>0.05),the GER and IPR in the EA non-acupoint group (P>0.05). Compared with the
      EA acupoint group, the symptom integrative score, IGF-1 and IGF-1 R levels were
      significantly increased in both EA non-acupoint and medication
      groups(P<0.05,P<0.01). CONCLUSIONS: EA stimulation can improve gastrointestinal
      motility and lower blood glucose in DGP rats, which may be closely associated
      with its effectiveness in reducing IGF-1 and IGF-1 R immunoactivity levels in
      gastric antrum.

PMID- 29072013
TI  - [Effects of Chiropractics on Intervertebral Disk Extracell Matrix and Metabolic
      Enzymes in Rats with Cervical Spondylosis].
AB  - OBJECTIVE: To observe the effect of chiropractics on intervertebral disk
      extracell matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, cellular collagen type
      II (COL-II), tissue inhibitor 1 of metalloproteinase (TIMP-1) and extracellular
      matrix (ECM) in the rats with cervical spondylosis, so as to explore its
      mechanism underlying improvement of cervical spondylosis. METHODS: A total of 40
      SD rats were randomized into a sham group, a model group, a chiropractics group
      and a mobic group, 8 rats in each one. The model was established by static
      dynamic imbalance method. The rats in the chiropractics group were treated with
      chiropractic therapy for two courses, 14 times a day and 14 days as a course. The
      rats in the mobic group were treated with intragastric administration of mobic.
      The expression of MMP-1, MMP-3, MMP-13, COL-II and TIMP-1 in the intervertebral
      disk tissue were detected by immunohistochemistry, and the protein expression of
      ECM was detected by Western blot. RESULTS: Compared with those in the sham group,
      the expressions of MMP-1, MMP-3, MMP-13 in the model group increased (all
      P<0.05), and COL-II, TIMP-1 decreased (both P<0.05).Compared with those in the
      model group, the expressions of MMP-1, MMP-3, MMP-13 in the chiropractics group
      and the mobic group decreased (all P<0.05), and COL-II, TIMP-1 increased (all
      P<0.05). Compared with that in the sham group, the expression of ECM protein in
      the model group decreased (P<0.05). Compared with that in the model group, the
      expression of ECM protein in the chiropractics group and the mobic group
      increased (both P<0.05). CONCLUSIONS: Chiropractics may improve the degeneration
      in rats with cervical spondylosis by regulating intervertebral disc ECM system
      and relevant metabolic enzymes.

PMID- 29072014
TI  - [Observation on Acupoint Sensitization Phenomenon in Experimental Myocardial
      Ischemia Rabbits].
AB  - OBJECTIVE: To develop an animal model suitable for the study of acupoint
      sensitization in myocardial ischemia(MI) animals by observing changes of the
      mechanical withdrawal threshold (pain threshold, PT). METHODS: Twenty New Zea
      land rabbits were randomly divided into control and model groups (n=10 in each
      group). The controllable MI model was set up by installing a balloon occluder at
      the left anterior descending branch of the left coronary artery. Air inflation of
      the balloon was given for 5 min/time, twice a day (4-hours' interval) for
      continuous 5 days (the first stage of MI), with one day's rest, then, another 5
      days' air inflation was conducted again (2nd stage of MI). Electrocardiogram
      (ECG) of the standard limb lead II was recorded for assessing MI, and myocardial
      2,3,5-triphenyltetrazolium chloride (TTC) staining was used to verify the degree
      of ischemic myocardium. The PT of the skin areas of "Neiguan" (PC 6), "Shenmen"
      (HT 7),"Taixi"(KI 3),hind paw(HP)was detected under conscious conditions,before
      MI, on day 8(after recovery from MI), day 14 (the first stage of MI), and day 20
      (the second stage of MI), respectively. RESULTS: The controllable MI model was
      successful due to a marked elevation of ECG ST II after inflation of the
      implanted balloon and a distinct recovery after balloon deflation (P<0.05). The
      myocardial TTC staining showed that the area of the myocardial necrosis was about
      10%. The PT values were significantly decreased in PC 6 area at the first stage
      of MI and in both PC 6 and HT 7 regions at the 2nd stage of MI (P<0.01),
      suggesting a close relationship between the acupoints of the Pericardium and
      Heart meridians and the heart in terms of the basic theory of Chinese medicine.
      CONCLUSIONS: MI may induce a reduction of PT of some related acupoints in MI
      rabbits, and the controllable MI model of the present study is helpful to the
      study of acupoint sensitization phenomenon after occurrence of visceral diseases.

PMID- 29072015
TI  - [Clinical Trials for Thyroidectomy Under Acupuncture-aided Anesthesia by Using
      Electroacupuncture or Transcutaneous Acupoint Electrical Stimulation of Different
      Acupoints].
AB  - OBJECTIVE: To observe the effectiveness of transcutaneous acupoint electrical
      stimulation (TAES) or electroacupuncture (EA) stimulation of different acupoints
      in combination with anesthetics in the management of thyroidectomy patients, so
      as to choose a better stimulating method and most effective acupoints for
      thyroidectomy. METHODS: A total of 216 thyroidectomy patients (ASA I-II grades)
      with thyroid gland adenoma, thyroid cyst or thyroid nodules from 3 hospitals (3
      research centers) were randomized into 6 groups, i.e., local anesthesia (LA,
      n=34), Futu (LI 18)-EA (n=36), Hegu (LI 4)-Neiguan (PC 6)-TAES (n=34), LI 4-PC 6
      EA (n=36), Yanglingquan (GB 34)-EA (n=36) and non-acupoint (NA, about 1.5 cm
      latero-posterior to KI 9)-EA (n=34) groups according to the hospitalizition
      sequence. For patients of the LI 18-EA, LI 4-PC 6-TAES/EA, GB 34 and non-acupoint
      EA groups, EA or TAES (2 Hz/100 Hz) was applied to the abovementioned bilateral
      acupoints or non-acupoint till the termination of the surgical operation. The
      surgery was conducted under anesthesia by local injection of 0.5% lidocaine and
      midazolam, and intravenous injection of fentanyl (for severe pain cases) 20 min
      after beginning of TAES or EA. The patients' scores of visual analogue scale
      (VAS),mean arterial pressure (MAP) and heart rate (HR) at the time-points of pre
      anesthesia (T 0), skin-incision (T 1), skin flap-freeing (T 2), anterior cervical
      muscle traction (T 3), thyroid upper/lower-pole-sectioning (T 4/T 5), and
      thyroidectomy (T 6), and the dosages of the administered fentanyl and lidocaine
      were recorded. RESULTS: Compared with the corresponding time-points of the non
      acupoint group, the VAS scores at T 1 and T 4 time-points in the LI 18-EA group
      and LI 4-PC 6-EA group, at T 1, T 5 and T 6 time-points in the LI 4-PC 6-TAES
      group were significantly lower (P<0.05). Compared with the corresponding time
      points of the LA group, the VAS scores at T 2, T 3, T 5 and T 6 time-points in
      the LI 18-EA group and LI 4-PC 6-EA group, at T 3, T 5 and T 6 in the LI 4-PC 6
      TAES group, and the MAP levels at T 2, T 3, T 4 and T 6 time-points in the LI 18
      EA group, at T 3, T 4 in the LI 4-PC 6-EA group, at T 3, T 4, T 6 in the LI 4-PC
      6 TAES group, as well as the HR levels at T 4, T 5 and T 6 in the LI 18-EA group,
      and at T 5, T 6 in the LI 4-PC 6-TAES group were significantly lower (P<0.05).
      The dosages of fentanyl in the LI 18-EA and LI 4-PC 6-TAES groups, and those of
      lidocaine in the LI 18-EA, LI 4-PC 6-EA and TAES groups were significantly lower
      relevant to the LA group and non-acupoint group (P<0.05). No significant
      differences were found between the LA and GB 34-EA groups, and between the LA and
      non-acupoint groups, as well as between the LI 4-PC 6-EA and LI 4-PC 6-TAES
      groups in the VAS scores, the MAP and HR levels, the dosages of lidocaine and
      fentanyl consumption (P>0.05). CONCLUSIONS: EA stimulation of both LI 18 and LI 4
      PC 6 and TAES of LI 4-PC 6 combined with anesthetics have a better effect in
      inducing analgesia and controlling MAP and HR, and need lower dosages of
      anesthetics for patients undergoing thyroidectomy, for which LI 18 and LI 4-PC 6
      are evidently superior to GB 34 and non-acupoint. Hence, combined EA or TAES and
      anesthetics is highly recommended for thyroidectomy.

PMID- 29072016
TI  - [Clinical Observation of Heat-sensitive Moxibustion Combined with Kegel Exercise
      Therapy for Female Stress Urinary Incontinence].
AB  - OBJECTIVE: To compare the clinical effects of heat-sensitive moxibustion combined
      with kegel exercise therapy and simple kegel exercise therapy on female stress
      urinary incontinence. METHODS: Forty-five female patients with stress urinary
      incontinence were randomly divided into a treatment group (n=23) and a control
      group (n=22). Kegel exercise therapy was applied in the two groups. Heat
      sensitive moxibustion was used at Zhongji (CV 3), Qihai (CV 6), Ciliao (BL 32)
      and Shen-shu (BL 23) in the treatment group, once a day for the first 10 times,
      and once every other day until 5 sessions were given, 10 times as one session. 1
      hour pad test, International Incontinence Advisory Board questionnaire (ICIQ-SF)
      and the number of urine leakage were observed before and after treatment. And the
      clinical effect was evaluated. RESULTS: The curative rate of 43.48%(10/23) and
      the total effective rate of 95.65%(22/23) in the treatment group were
      respectively better than those of 18.18% (4/22) and 63.64%(14/22) in the control
      group (both P<0.05). After treatment, 1-hour pad test and ICIQ-SF score were
      lower than those before treatment in the two groups, and the number of urine
      leakage decreased (all P<0.01). The above three indexes of the treatment group
      were better than those of the control group (all P<0.01). CONCLUSIONS: Heat
      sensitive moxibustion combined with kegel exercise therapy achieves better effect
      than simple kegel exercise therapy on female stress urinary incontinence.

PMID- 29072017
TI  - [Effect of Acupuncture at Thirteen Evil Acupoints on Liver Function, and the
      Contents of Blood Ammonia and beta-endorphin in Patients with Hepatic
      Encephalopathy].
AB  - OBJECTIVE: To observe the therapeutic effect of acupuncture at thirteen evil
      acupoints in patients with hepatic encephalopathy, and to explore its possible
      mechanism. METHODS: Patients with hepatic encephalopathy were randomly divided
      into acupuncture group (n=38) and western medicine group (n=36). Patients in the
      western medicine group were treated by intravenous injection of aspartate
      ornithine and branched chain amino acids, and those in the acupuncture group were
      treated with acupuncture at thirteen evil acupoints on the basis of the western
      medicine. All the patients were treated for 1 week. The liver function and blood
      ammonia were measured by automatic biochemical analyzer. The changes of plasma
      beta-endorphin were measured by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Following the treatment, of the 36 and 38 hepatic encep-halopathy
      patients in the western medicine and acupuncture groups, 12 and 18 experienced a
      marked improvement in their symptoms, 13 and 16 were effective, and 11 and 4
      invalid, with the effective rates being 69.4% and 89.5%, respectively. Compared
      with pre-treatment, the levels of serum aspartate aminotransferase, alanine
      aminotransferase, total bilirubin, and plasma beta-endo-rphin and blood ammonia
      were significantly lower in both western medicine and acupuncture groups(P<0.01),
      and the therapeutic effects of the acupuncture group were obviously superior to
      those of the western medicine group in the above mentioned indexes (P<0.05,
      P<0.01). CONCLUSIONS: Treatment of acupuncture at thirteen evil acupoints
      combined with western medicine can enhance the curative effect of hepatic
      encephalopathy, improve patients' liver function and decrease the levels of
      plasma ammonia and beta-endorphin.

PMID- 29072018
TI  - [The Therapeutic Effect of Acupuncture on Cerebral Palsy in Children with
      Language Retardation Using the Midnight-noon Ebb-flow Method Combined with
      Syndrome Differentiation].
AB  - OBJECTIVE: To determine the clinical effect of acupuncture treatment on cerebral
      palsy in children with language retardation using the Midnight-noon Ebb-flow
      method combined with syndrome differentiation. METHODS: One hundred and thirty
      six children with cerebral palsy and language retardation were randomly divided
      into control group and treatment group. The control group received routine
      treatment for language rehabilitation, while the treatment group received
      acupuncture treatment using the Midnight-noon Ebb-flow method combined with
      syndrome differentiation for 3 months based on language rehabilitation. The
      children were assessed by sign-significate relations for language comprehension
      and language expression before and after treatment. RESULTS: After treatment, the
      development quotient scores for language comprehension and language expression
      were (60.37+/-4.64) and (51.13+/-3.81) in the control group, and (73.54+/-4.73)
      and (64.08+/-3.93) in the treatment group, and the differences were statistically
      significant compared with those before treatment in the same one group,
      respectively(P<0.05, P<0.01). The effects of the treatment group were
      statistically better than those of the control group (P<0.05). CONCLUSIONS:
      Acupuncture treatment using the Midnight-noon Ebb-flow method combined with
      syndrome differentiation has a better therapeutic effect in improving language
      comprehension and language expression, and promoting language development in
      children with cerebral palsy.

PMID- 29072020
TI  - ["Xingnao Kaiqiao" Needling Stimulation Promotes Resuscitation of General
      Anesthesia Patients Undergoing Anodynia Gastrointestinal Endoscopy].
AB  - OBJECTIVE: To observe the effect of "Xingnao Kaiqiao" needling on the recovery of
      general anesthesia in mid-aged and elderly patients undergoing painless
      gastrointestinal endoscopy. METHODS: A total of 140 patients were randomly
      divided into control and treatment groups, with 70 cases in each group. After
      termination of the endoscopy, patients of the treatment group received
      acupuncture stimulation of Neiguan (PC 6), Shuigou (GV 26) and Sanyinjiao (SP 6)
      with sterilized disposable filiform needles which were manipulated with twirling
      reducing method for 3 min in PC 6, with lifting-thrusting reinforcing method in
      SP 6, and with bird-peck needling in GV 26. The patients of the control group
      were not given any treatment. Before, the immediate time of termination of the
      endoscope examination, resuscitation and 10 min after the endoscope examination,
      the mini-mental state examination (MMSE) scores were obtained to assess the
      patients' recognition function. The Bi-spectral Index (BIS) values were recorded
      to assess the patients' depth of sedation and anesthesia, and the Observer's
      Assessment of Alertness/Sedation Scale (OAA/S) was used to evaluate the
      resuscitation/sedation level. RESULTS: Compared with the control group, the MMSE
      score of the treatment group was significantly higher at the 10th min after
      endoscope examination (P<0.05),suggesting an improvement of the cognitive
      function after acupuncture intervention. The duration from general anesthetic
      state (BIS values=40-60 points) to mild sedation (BIS values=80-90 points) was
      significantly shorter in the treatment group than in the control group (P<0.05).
      No significant differences were found between the two groups in the OAA/S score
      at the 10th min after endoscope (P>0.05). CONCLUSIONS: "Xingnao Kaiqiao" needling
      stimulation has a significant effect on the recovery of middle-aged and elderly
      patients undergoing painless gastroscopy during general anesthesia.

PMID- 29072019
TI  - [Clinical Studies of Abdominal Acupuncture Combined with Warm Needling on Knee
      Osteoarthritis].
AB  - OBJECTIVE: To explore the clinical effects of abdominal acupuncture combined with
      warm needling on knee osteoarthritis (KOA). METHODS: Eighty-six patients with KOA
      were divided into a treatment group and a control group according to the digital
      random table, 43 cases in each one. In the treatment group, patients were treated
      with abdominal acupuncture at Zhongwan (CV 12), Guanyuan (CV 4) and Huaroumen (ST
      24), Wailing (ST 26) and Xiafengshidian (Extra) on the affected side, as well as
      warm needling at Neixiyan (EX-LE 4), Dubi (ST 35), Heding (EX-LE 2), Liangqiu (ST
      34) and Xuehai (SP 10) of the affected side. In the control group, warm needling
      was given. All the patients were treated 5 times a week for 4 weeks. Each
      dimension score of Western Ontario and McMaster University (WOMAC) osteoarthritis
      index scale and health survey 36-item short form (SF-36) of the two groups was
      compared before and after treatment. Enzyme-linked immunosorbent assay was
      applied to test serum vascular endothelial growth factor (VEGF) and angiopoietin
      1(Ang-1). RESULTS: Compared with those before treatment, the scores of pain,
      stiffness, joint function of WOMAC scale and serum VEGF, Ang-1 of the two groups
      were lower after treatment (all P<0.01), and each dimension score of SF-36 scale
      increased significantly (all P<0.01). Each dimension score of WOMAC scale and
      serum VEGF, Ang-1 in the treatment group were lower than those in the control
      group after treatment (all P<0.01), and each score of SF-36 was higher (all
      P<0.01). The total effective rate of 93.0% (40/43) in the treatment group was
      higher than 74.4% (32/43) in the control group (P<0.05). CONCLUSIONS: Abdominal
      acupuncture combined with warm needling can effectively alleviate pain and
      stiffness, improve the function of knee joint and quality of life, with definite
      effect for KOA. The mechanism may be related to the decreasing of serum VEGF and
      Ang-1.

PMID- 29072021
TI  - [Method of Epidemiological Study on the Clinical Safety of Moxa Smoke].
AB  - With the development of moxibustion use, increasing attention has focused on the
      safety of moxa smoke. Evaluation of the safety of moxa smoke has now become an
      urgent problem in moxibustion clinical practice. An epidemiological study could
      provide direct evidence of the safety of moxa smoke, but has not yet been
      comprehensively and systematically studied. In the present paper, the authors
      discuss the research methods used in epidemiological studies of the clinical
      safety of moxa smoke and some key problems regarding definition of the exposed
      population, the determination of exposure outcome, the choice of psychological
      measuring tool and the assessment of exposure level.

PMID- 29072022
TI  - [Progress on the Relationship Between the Regulation of Gastrointestinal System
      Function by Acupuncture and Central Nuclei].
AB  - Acupuncture has a good curative effect in the treatment of gastrointestinal
      system diseases, such as functional dyspepsia, ulcerative colitis, and
      constipation. The central nuclei which are involved in the mechanism of
      acupuncture in regulating the gastrointestinal system have become a research
      hotspot in recent years. In the present paper, the authors summarized the effect
      of acupuncture and the central nervous system on gastrointestinal function
      regulation. It was found that the regulation of gastrointestinal function by
      acupuncture involved many brain regions such as the amygdala, paraventricular
      nucleus, locus coeruleus, raphe nucleus, and dorsal nucleus of the vagus nerve.
      Of these, the limbic brain region had the closest relation. However, the included
      studies were animal experiments, which involved less research on nuclear group
      interactions. The role of central nuclei in the regulation of gastrointestinal
      function by acupuncture is unclear. Thus, the introduction of more advanced brain
      imaging techniques to observe brain dysfunction of central nuclei and the
      relativity of acupuncture in regulating gastrointestinal function will be the
      focus in the future study, which will contribute to determining the effective
      mechanism of acupuncture and moxibustion.

PMID- 29072023
TI  - [Prospects and Progress on the Mechanisms of Acupuncture Underlying Improvement
      in Diabetic Gastroparesis].
AB  - Diabetic gastroparesis (DGP) is an important complication of diabetes, and
      seriously impacts the patient's quality of life. In the present paper, the
      authors summarize national and international research on the mechanism of
      acupuncture therapy in improving DGP and the pathogenesis of DGP over the past 10
      years. The authors illustrate the mechanism of acupuncture underlying the
      improvement in DGP as follows:1) the effect on autonomic nerves and neurons of
      the central nervous system; 2) promoting restoration of the enteric nervous
      system; 3) the effect on Cajal interstitial cells; 4) improving gastrointestinal
      hormone disorder; 5) improving hyperglycemic state; 6) the effect on gastric
      smooth muscle. The authors also put forward some suggestions for future research
      on the mechanisms of acupuncture in DGP.

PMID- 29072025
TI  - Does small-sided games training improve physical fitness and team-sport-specific
      skills? A systematic review and meta-analysis.
AB  - INTRODUCTION: This paper aimed to systematically review the training effects of
      small-sided games (SSG) on physical fitness and specific skills related to team
      sport according to the level of play and the period of the season. EVIDENCE
      ACQUISITION: The search covered the following electronic databases (PubMed,
      Google Scholar, and ScienceDirect). The publications' search period ranged from
      2000 to 2016. The terms (small-sided game, training, skill-based game, aerobic
      fitness, sprint, agility, jump and team sports) were used either singularly or
      combined in a systematic sequence. Appraisal of 16 articles (15 were analyzed)
      was performed after the application of exclusion criteria and quality assurance
      processes and the standardized mean effects were measured using random effects.
      EVIDENCE SYNTHESIS: The results revealed that SSG training had a large beneficial
      effect on maximal oxygen uptake VO2max (effect size 1.94; 95% CI: 0.15, 3.74;
      I2=94%), agility (-1.49; 95% CI: -2.27, -0.71; I2=80%), and repeated sprint
      ability (-1.19; 95% CI: -2.17, -0.21; I2= 53%). There was a moderate beneficial
      effect on 10- and 20-m sprint performance (-0.89; 95% CI: -1.7, -0.07; I2=88%),
      jump height (0.68; 95% CI: 0.03, 1.33; I2= 79%), and intermittent endurance
      (0.61; 95% CI: 0.17, 1.05; I2= 0%). The results also showed greater positive
      effects on specific skills (specific endurance and agility tests and techniques)
      after SSG when compared with generic or agility training. CONCLUSIONS: Small
      sided games may represent an effective strategy of multicomponent training that
      can induce greater positive effects on specific skills tasks when compared with
      interval or agility training and moderate to large improvements in team sport
      related physical fitness.

PMID- 29072026
TI  - Functional outcomes of kinesio taping versus standard orthotics in the management
      of shin splint.
AB  - BACKGROUND: Exercise-related or lower-limb overuse injury characterized by pain
      located between the knee and the ankle that occurs during activity is commonly
      referred to as shin splint. Hyperpronation is considered the ultimate culprit in
      the development of overuse injuries such as shin splint. This study endeavors to
      compare the functional outcomes of the most commonly used anti-pronation
      techniques, kinesio taping and standard orthotics. METHODS: A total of 40
      subjects (mean age, 24.16+/-2.6 years) with symptoms of shin splint participated
      in the current study. These subjects were randomly allocated to two groups
      (N.=20) and underwent anti-pronation kinesio taping and standard orthotics,
      respectively. The functional outcomes were assessed using the navicular drop
      test, visual analog scale, and hop distance. RESULTS: The kinesio taping
      intervention group showed significant improvements in pain and hop distance
      compared to the standard orthotics intervention group, whereas an insignificant
      intergroup difference was observed for the navicular drop test. Patients in both
      groups benefited, but the response to kinesio taping was better than that to
      orthotics. CONCLUSIONS: Kinesio taping played a vital role in improving
      functional outcomes compared to orthotics by reducing pain and improving
      functional activity in patients with shin splint; however, navicular drop
      correction did not occur using either intervention.

PMID- 29072024
TI  - [Research of Characteristics of Stimulation Methods and Application of Acupoint
      in Auricular Needle Therapy Based on Data Mining].
AB  - In the present paper, using data mining technology,the authors downloaded
      information from databases on auricular needle therapy, and obtained data samples
      from journals and academic dissertations involving the application of auricular
      needle therapy to treat diseases, and then screened, audited, and extracted the
      data and performed a statistical analysis. The authors extracted data on the
      application of auricular needle therapy in the stimulation methods of medicine
      (needling instrument), selection of the side of ear to treat disease and the
      number of times the ear was pressed per day and the compression time. In the
      stimulation methods, the needling instrument varied, the seeds of cowherb Semen
      Vaccariae were applied in 60.89% of the total stimulation methods. The number of
      times the ear was pressed per day and the compression time in the clinic were
      optional. The main points in auricular needle therapy were the contralateral
      side; there was no significant difference in the effect of a single side or both
      sides of the ear to treat disease.

PMID- 29072027
TI  - Effect of stretching-based rehabilitation on pain, flexibility and muscle
      strength in dancers with hamstring injury: a single-blind, prospective,
      randomized clinical trial.
AB  - BACKGROUND: Hamstring injuries commonly occur in mainstream sports and
      occupations that involve physical activity. We evaluated the effect of a
      stretching-based rehabilitation program on pain, flexibility, and strength in
      dancers with hamstring injuries. METHODS: Sixteen Korean traditional dancers with
      unilateral hamstring injuries were included and randomly assigned to a
      rehabilitation or control group. The rehabilitation group received stretching
      based rehabilitation for 8 weeks, which comprised simple static stretches and
      basic range of motion (ROM) exercises, such as static and active stretching,
      concentric and eccentric ROM training, and trunk stabilization exercises. The
      control group received conventional treatment with analgesics and physical
      therapy. Outcomes were assessed before and after the interventions in both groups
      by comparing the Visual Analog Scale (VAS) score for pain, straight leg raise ROM
      Test for hamstring muscle flexibility, and isometric strength test for hamstring
      muscle strength. RESULTS: Subjects who underwent rehabilitation showed
      significant improvements in VAS score for pain (P=0.017) and ROM for flexibility
      (P<0.001). Muscle strength also increased after the rehabilitation program
      (P<0.05). CONCLUSIONS: This rehabilitation program effectively decreases pain and
      increases flexibility and strength in patients with hamstring injury. The data
      indicate that a stretching-based rehabilitation program can help promote
      functional recovery from hamstring injury.

PMID- 29072028
TI  - Differences in salivary hormones and perception of exertion in elite women and
      men volleyball players during tournament.
AB  - BACKGROUND: Sports tournaments induce both psychological and physiological
      stress, which seems to be different between men and women. Competition induces
      anticipatory rises in testosterone and cortisol levels, which may affect
      performance and physical exertion during tournaments. The aim of this study was
      to compare the changes in salivary cortisol and testosterone concentrations
      between men and women during an official volleyball tournament and to test
      potential correlations between changes in these hormones and perceived exertion
      after match. METHODS: Three matches of each team were assessed in the group stage
      of the Men and Women South American Volleyball Championship. Salivary cortisol
      and testosterone levels were measured in the fasting state, before and after each
      match. The rate of perceived exertion (RPE) was assessed after each match.
      RESULTS: Fasting cortisol concentrations were higher in women than men (~25%,
      P<0.001) while fasting testosterone was higher in men than women (~46%, P<0.001).
      Cortisol concentration increased only after the second match in men (+53.7%,
      P<0.001). Testosterone concentration was low before and after the third match in
      men (P<0.001) while it was elevated after the third match in women (P=0.003). The
      rate of perceived exertion was correlated with the change in testosterone levels
      due to the matches in both women (r=0.33; P=0.04) and men (r=0.44; P=0.02), which
      was not observed for cortisol concentrations. CONCLUSIONS: These results indicate
      that women have higher fasting cortisol, but lower fasting testosterone
      concentrations than men during a volleyball tournament. Thus, hormonal responses
      of women and men are different and related to their effort during the matches.

PMID- 29072029
TI  - Adapted physical activity and stroke: a systematic review.
AB  - INTRODUCTION: Stroke is one of the most significant social and health issues at
      the global level. The integration of adapted physical activity and exercise into
      the rehabilitation process and in the post- rehabilitation stage could represent
      a successful action aimed at the functional and cognitive recovery of brain
      injured individuals following a stroke. The objective of this systematic review
      was to analyze the role of physical activity in the post-stroke period referring
      not only to the rehabilitation stage but also to the post-rehabilitation one.
      EVIDENCE ACQUISITION: The systematic review was conducted following the Preferred
      Reporting Items for Systematic reviews and Meta-Analyses methodology. We
      systematically reviewed studies published since 2005. The databases used were
      PubMed and Scopus. EVIDENCE SYNTHESIS: Fourteen articles were included in our
      review. The evidence supporting the use of physical activity and exercise in
      stroke survivors in order to maintain adequate levels of their motor autonomy and
      to improve their physical and psychological health increased over time.
      CONCLUSIONS: Physical activity and exercise contribute to the improvement of
      health and quality of life in stroke survivors. Moreover, it contributes to
      maintain functional autonomy, reduces the risk of new cerebrovascular events and
      encourages socialization if practiced in a group.

PMID- 29072030
TI  - Injuries in recreational and competitive surfers: a nationwide study in Portugal.
AB  - BACKGROUND: Surfers are subjected to external factors (ocean currents, wind
      orientation, wave size, contact with the board and other surfers) that require
      quick and efficient adaptations, increasing the risk of injury while riding
      waves. This study aimed to determine the incidence of injuries over a 12-month
      period in Portuguese surfers and to analyse the associated factors. METHODS: The
      sample included 1,016 Portuguese surfers, aged between 8 and 64 years; 853 (84%)
      were male. A questionnaire was administered during the stages of the Regional
      Circuit Surf of Portugal. RESULTS: Three hundred and one (29.6%) surfers had an
      injury in the previous year, with a total of 398 injuries. There were 1.23
      injuries per 1,000 hours of surfing. The most common injuries were lacerations
      (23.5%), located in the knee and leg (16.7%). Impacts of the board (27.1%), and
      injuries during paddling (17.9%) were the most prevalent injury mechanisms.
      Competitor surfers presented a higher risk of sustaining surfing- related
      injuries than recreational surfers (odds ratio= 1.81; 95%CI: 1.26-2.62; p=0.002).
      Individuals who had surfed for less than five years were at 1.65 more risk
      (95%CI: 1.13- 2.39; p=0.009) than those who had surfed for more than 10 years;
      surfers who trained at least three times a week had 1.42 the risk (95%CI: 1.08
      1.87; p=0.011) than those who trained less. CONCLUSIONS: Injuries were frequent
      among Portuguese surfers, with specific affected body areas, mainly caused by
      impact with the board. It s necessary to create injury prevention strategies,
      including specific trainings and the use of protection material.

PMID- 29072032
TI  - Training-induced annual changes in red blood cell profile in highly-trained
      endurance and speed-power athletes.
AB  - BACKGROUND: An extensive body of literature exists on the effects of training on
      haematological parameters, but the previous studies have not reported how
      hematological parameters respond to changes in training loads within consecutive
      phases of the training cycle in highly-trained athletes in extremely different
      sport disciplines. The aim of this study was to identify changes in red blood
      cell (RBC) profile in response to training loads in consecutive phases of the
      annual training cycle in highly-trained sprinters (8 men, aged 24 +/- 3 years)
      and triathletes (6 men, aged 24 +/- 4 years) who competed at the national and
      international level. METHODS: Maximal oxygen uptake (VO2max), RBC, haemoglobin
      (Hb), haematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular
      haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and RBC
      distribution width (RDW) were determined in four characteristic training phases
      (transition, general subphase of the preparation phase, specific subphase of the
      preparation phase and competition phase). RESULTS: Our main findings are that (1)
      Hb, MCH and MCHC in triathletes and MCV in both triathletes and sprinters changed
      significantly over the annual training cycle, (2) triathletes had significantly
      higher values than sprinters only in case of MCH and MCHC after the transition
      and general preparation phases but not after the competition phase when MCH and
      MCHC were higher in sprinters and (3) in triathletes, Hb, MCH and MCHC
      substantially decreased after the competition phase, which was not observed in
      sprinters. The athletes maintained normal ranges of all haematological parameters
      in four characteristic training phases. CONCLUSIONS: Although highly-trained
      sprinters and triathletes do not significantly differ in their levels of most
      haematological parameters, these groups are characterized by different patterns
      of changes during the annual training cycle. Our results suggest that when
      interpreting the values of haematological parameters in speed-power and endurance
      athletes, a specific phase of the annual training cycle should be taken into
      account.

PMID- 29072031
TI  - Wellness, muscle soreness and neuromuscular performance during a training week in
      volleyball athletes.
AB  - BACKGROUND: The purpose of the current study is to analyse the acute effects of
      volleyball training and to compare the responses of different perceptual and
      neuromuscular measures to overall training load. METHODS: The training load,
      wellness, neuromuscular performance and perceptual measures of soreness of 13
      highly-trained volleyball athletes (18 +/- 1 years; 187.1 +/- 7.0 cm; 84.3 +/-
      10.3 kg) representing the Portugal under-19 national team were monitored during a
      training week. Perceptual fatigue was obtained in the morning of every training
      day from a 5-item wellness questionnaire (sleep, soreness, mood, fatigue, stress)
      and a muscle soreness questionnaire surveying 9 different muscle sites from each
      side of the body. Neuromuscular performance was obtained from a countermovement
      jump (CMJ) on the morning of training day's 1, 2, 4 and 5. RESULTS: Small effect
      sizes in CMJ's were observed on days 4 and 5 when compared to baseline. Wellness
      items were affected by training, with the fatigue item and the total score being
      the most affected. Muscle soreness increased from day 2 until day 5 in comparison
      to baseline across various muscle sites and regions. Nevertheless, responses in
      soreness were different from muscle sites, average of muscle sites and a single
      question of muscle soreness. CONCLUSION: Volleyball training elicits meaningful
      changes in physiological and perceptual measures of fatigue and muscle soreness,
      as evident from day 2 until the last training day of the week. Muscle soreness
      scores obtained from different muscle sites may provide important information to
      coaches.

PMID- 29072033
TI  - Technical strategy of triple jump: differences of inverted pendulum model between
      hop-dominated and balance techniques.
AB  - BACKGROUND: The present study aims to cross-sectionally clarify the
      characteristics of the motions of an inverted pendulum model, a stance leg, a
      swing leg and arms in different triple-jumping techniques to understand whether
      or not hop displacement is relatively longer rather than step and jump
      displacements. METHODS: Eighteen male athletes performed the triple jump with a
      full run-up. Based on the technique of the jumpers, they were classified as hop
      dominated (n = 10) or balance (n = 8) jumpers. The kinematic data were calculated
      using motion capture and compared between the two techniques using the inverted
      pendulum model. RESULTS: The hop-dominated jumpers had a significantly longer hop
      displacement and faster vertical centre-of-mass (COM) velocity of their whole
      body at hop take-off, which was generated by faster rotation behaviours of
      inverted pendulum model and faster swinging behaviours of arms. Conversely,
      balance jumpers had a significantly longer jump displacement and faster
      horizontal COM velocity of their whole body at take-off, which was generated by a
      stiffer inverted pendulum model and stance leg. CONCLUSIONS: The results
      demonstrate that hop-dominated and balance jumpers enhanced each dominated-jump
      displacement using different swing- and stance-leg motions. This information may
      help to enhance the actual displacement of triple jumpers using different jumping
      techniques.

PMID- 29072034
TI  - Potential effect of exercise in ameliorating insulin resistance at transcriptome
      level.
AB  - BACKGROUND: Insulin resistance can lead to the pathogenesis of type 2 diabetes
      and exercise can increase insulin sensitivity. And different exercises may have
      different influences on the mitigation of insulin resistance. It's still unclear
      how exercise affects inherited insulin resistance at transcriptome level. The
      purpose of our study was to analyze the potential effects of exercise in
      ameliorating insulin resistance at transcriptome level. METHODS: Herein, we
      analyzed two skeletal muscle transcriptome profiles, including gene profiles
      between inherited insulin resistant patients and matched healthy controls, and
      between trained and sedentary subjects (young and old subjects, respectively).
      RESULTS: Analysis of differentially expressed genes revealed that 12 genes (SGK1,
      LOC101929876, MYL5, COL6A3, MLF1, LUM, MSTN, COL1A2, COL3A1, IL32, IRS2 and ID1)
      associated with insulin resistance were reversed by exercise in young subjects,
      while six genes (MSTN, CFHR1, PFKFB3, IL32, RGCC and NMRK2) were identified in
      old subjects, suggesting that those genes play potential roles in insulin
      resistance response to exercise. In addition, we observed that two insulin
      resistance-related genes, MSTN and IL32, were identified in muscle cells of both
      young and old subjects, indicating their important roles in the mechanisms behind
      the beneficial effects of exercise on humans with inherited insulin resistance.
      Several pathways were also identified, such as "collagen metabolic process",
      "focal adhesion" and "negative regulation of myoblast differentiation".
      CONCLUSIONS: Taken together, our findings provide novel markers in insulin
      resistant patients and exercise, and some valuable information for future
      functional studies on how exercise ameliorating insulin resistance.

PMID- 29072035
TI  - Relation between lifestyle behaviors and body composition patterns among healthy
      young Italians: a cross-sectional study.
AB  - BACKGROUND: Negative lifestyle factors affect health outcomes adversely. The aim
      of the study was to assess body composition parameters and their relationship to
      several lifestyle behaviors among young Italian adults. METHODS: A cross
      sectional study was carried out on a sample of university students (N.=200; 50%
      males; 21.9+/-2.0 years). Anthropometric and bio-impedance traits were directly
      measured. Behavioral data (physical activity, alcohol consumption and smoking
      data) were collected by a self-administered questionnaire. Quantitative and
      qualitative data were used to characterize and compare across participants by
      univariate and multivariate analyses. RESULTS: The prevalence of subjects at risk
      (above the cut-points) was 3% in men and 2% in women for generalized obesity
      (BMI); 1% in women for centralized obesity (waist circumference); 12% in men and
      5% in women for obesity (fat percentage). Unhealthy behaviors were infrequent in
      our sample. Multiple linear regression analyses showed that percentage of fat
      mass and fat-free mass were closely related to sex and structured physical
      activity: fat percentage decreased and fat free mass increased with the
      increasing of sport practice. CONCLUSIONS: Our findings highlight new evidence on
      the particular impact of structured physical activity on body composition in
      young adults. Interventions should focus on the optimization of youth health
      behaviors.

PMID- 29072036
TI  - Oxidative stress, lipid peroxidation indexes and antioxidant vitamins in long and
      middle distance athletes during a sport season.
AB  - BACKGROUND: The main objective of this study was to observe any changes and
      possible adaptations produced in MDA and antioxidants vitamins on plasma and
      erythrocytes in endurance male athletes among an athletic season (12 months).
      METHODS: Twenty three long and middle distance male athletes participated in this
      study. Basal MDA on plasma and antioxidant vitamins in plasma and erythrocytes
      were measured at four moments along the season (0, 3, 6 and 9 months). Fatty acid
      concentrations in erythrocytes were obtained to determine lipid peroxidation
      indexes. RESULTS: In plasma, Vitamin C suffered significant decreases at 3 and 6
      months compared with the begin (p<0.01), and an increase at 9 months, compared
      with 3 months. On the other hand, vitamin A level was significantly lower at 9
      months compared with the other periods (p<0.01 compared with 0 and 6 months;
      p<0.05 compared with 3 months). In erythrocytes, significant decreases were
      observed in vitamin E among the season at 6 months and an increase from 6 to 9
      months (p<0.05). Vitamin A suffers a significant decrease in both for competitive
      periods, at 3 and 9 months, compared with the begin of the season. The most of
      changes in lipid peroxidation indexes were produced along the firsts 3 months.
      CONCLUSIONS: i) physical training improves the antioxidant systems in order to
      reduce lipid peroxidation in trained athletes along the season; ii) PUFA/SFA
      ratios seem more reliable than MDA to observe oxidative stress.

PMID- 29072037
TI  - Excess post-exercise oxygen consumption and fat oxidation in recreationally
      trained men following exercise of equal energy expenditure: comparisons of
      spinning and constant endurance exercise.
AB  - BACKGROUND? Spinning exercise is one of the most popular types of exercise in
      fitness industry. Its effects on the post exercise metabolism compared to the
      isocaloric cyclic endurance exercise are not fully understood. The aim of the
      present study was to compare the effects of isocaloric (299.1 +/- 10.8 kcal)
      spinning vs endurance exercise on fat and carbohydrate utilization, glucose,
      lactate, glycerol and NEFA blood concentration during exercise and recovery.
      METHODS? Six recreationally active males (age: 23.5 +/- 0.71), were tested in two
      conditions: 1) 30-min spinning; 2) isocaloric continuous exercise. Each trial was
      followed by a 3-h recovery. Rates of carbohydrate and fat oxidation, the blood
      glucose, lactate, glycerol and NEFA concentration were assessed at rest, during
      exercise and recovery. RESULTS? Spinning induced significantly higher fat and
      lower carbohydrate oxidation rate during a recovery period in comparison to
      isocaloric endurance exercise trial. Spinning induced almost six-fold higher
      increase in lipid to carbohydrate oxidation rate ratio at the beginning of second
      hour of post-exercise period in comparison to constant intensity trial and
      reached similar values at 3 hours after exercise. Blood lactate was higher (p <
      0.01) at the end of exercise in spinning than continuous exercise (8.57 +/- 0.9
      vs 0.72 +/- 0.1 mmol.L-1), but became similar at the 60 min of recovery.
      CONCLUSIONS? These data indicate that spinning induces higher metabolic responses
      during recovery period, and most effectively shifts the pattern of substrate use
      toward lipids vs isocaloric endurance exercise.

PMID- 29072038
TI  - Complex exercise intervention on Chinese patients with type 2 diabetes.

PMID- 29072039
TI  - Effects of Chinese adults' body mass indexes, body fat percentages, and fat free
      masses on energy consumption during badminton.

PMID- 29072040
TI  - The functional manual therapy intervention in infants with nonsynostotic
      plagiocephaly: a pilot study.
AB  - BACKGROUND: To document the evolution of cranial asymmetries in infants with
      signs of nonsynostotic occipital plagiocephaly (NSOP) who were undergo to many
      functional manual therapy treatments (in addition to the standard positioning
      recommendations) as well as to determine the feasibility of this methodology to
      conduct an outcome research investigating the impact of this intervention for
      infants with NSOP. METHODS: Pilot clinical standardization project using pre-post
      design in which 10 infants participated. Nine infants presented an initial
      Oblique Diameter Difference Index (ODDI) over 104%, three an initial Ear
      Deviation Index (EDI) over 4%, and three a Cranial Proportional Index (CPI) over
      90%. INTERVENTIONS: Infants received three functional manual therapy treatments
      for week during the first month of intervention and two ones for week during the
      second month. RESULTS: Plagiocephalometric measurememts were administered at the
      first assessment pre-intervention (T0), after 30 days (+/-5) (T1) and at a third
      time after 60 days (+/5) of treatment (T2). RESULTS: 9/10 participants showed a
      significant decrease in ODDI under 104% between T0 and T2 assessments. 5/10
      infants showed an EDI under 4%, and 3/10 showed a value about 0%. 3/10 maintained
      their CPI over 90% with a considerable decrease. CONCLUSIONS: These clinical
      findings support the hypothesis that functional manual therapy treatments
      contribute to the improvement of cranial asymmetries in infants younger than 6.5
      months old presenting with NSOP.

PMID- 29072041
TI  - Epidemiology of Serratia marcescens infections in NICU of a teaching and research
      hospital in northern Italy.
AB  - BACKGROUND: Serratia marcescens (Sm) is a known cause of infection and
      colonization in neonates receiving intensive care. The aim of this study was to
      identify the risk factors for colonization and infection with Sm in Neonatal
      Intensive Care Unit (NICU) of a tertiary care Hospital. METHODS: A casecontrol
      study was conducted from January to December 2011 in neonates admitted to the
      NICU. Cases are patients with a microbiologically confirmed infection or
      colonization, controls were randomly chosen among patients admitted to the same
      NICU. RESULTS: Globally, 39 acquired infections or colonizations were identified.
      Among factors related to pregnancy, only premature delivery was independently
      associated to the risk of infection; as well as mechanical ventilation and
      catheterization for parenteral nutrition, considering indwelling devices.
      Prolonged administration with antibiotics were also related to the risk of
      infection. Among Sm strains which have been tested to antibiotics, all have been
      resistant to amoxicillin/clavulanic acid and to colistin. CONCLUSION: This study
      confirms the association between Sm infection or colonization and low gestational
      age. Invasive medical devices and medications, strictly necessary in caresupport
      of preterm neonates, are likely related to Sm infection too. Preventive control
      strategies are expected to be effective in the control of Sm spread in NICUs.

PMID- 29072042
TI  - Active exergames to improve cognitive functioning in neurological disabilities: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Exergames represent a way to perform physical activity through
      active video games, serving as potentially useful tool in the field of
      neurorehabilitation. However, little is known regarding the possible role of
      exergames in improving cognitive functions in persons suffering from neurological
      disabilities. EVIDENCE ACQUISITION: A search for relevant articles was carried
      out on PubMed/Medline, Scopus, PEDro, and Google Scholar. Only randomized
      controlled studies and non-randomized but controlled studies were retained. The
      following additional inclusion criteria were applied: studies focused on physical
      activity interventions carried out by means of exergames; populations targeted
      were affected by neurological disabilities; and reported results were related to
      cognitive outcomes. We calculated standardized mean differences (SMD) and pooled
      results using a random effects meta-analysis. EVIDENCE SYNTHESIS: Of 520
      abstracts screened, thirteen studies met the criteria to be included yielding a
      total of 465 participants, 233 randomized to exergames, and 232 allocated to the
      alternative or no intervention. The included studies varied in terms of studied
      populations (e.g., multiple sclerosis, post-stroke hemiparesis, Parkinson's
      disease, dementia, dyslexia, Down syndrome), type and duration of interventions,
      and cognitive outcome measures. Exergames significantly improved executive
      functions (SMD=0.53, P=0.005; 8 studies, N.=380) and visuo-spatial perception
      (SMD=0.65, P<0.0001; 5 studies, N.=209) when compared to the alternative or no
      intervention. There were no significant differences for attention (SMD=0.57,
      P=0.07; 7 studies, N.=250) and global cognition (SMD=0.05, P=0.80; 6 studies,
      N.=161). CONCLUSIONS: Exergames are a highly-flexible tool for rehabilitation of
      both cognitive and motor functions in adult populations suffering from various
      neurological disabilities and developmental neurological disorders. Additional
      high-quality clinical trials with larger samples and more specific cognitive
      outcomes are needed to corroborate these preliminary findings. CLINICAL
      REHABILITATION IMPACT: Exergames could be considered either as a supplemental
      treatment to conventional rehabilitation, or as strategy to extend benefits of
      conventional programs at home.

PMID- 29072043
TI  - Evaluation of a self-administered transcutaneous electrical stimulation concept
      for the treatment of spasticity: a randomized placebo-controlled trial.
AB  - BACKGROUND: Spasticity is a common consequence of injury to the central nervous
      system negatively affecting patient's everyday activities. Treatment mainly
      consists of training and different drugs, often with side effects. There is a
      need for treatment options that can be performed by the patient in their home
      environment. AIM: The objective of this study was to assess the effectiveness of
      an assistive technology (AT), Mollii(r), a garment with integrated electrodes for
      multifocal transcutaneous electrical stimulation intended for self-treatment of
      spasticity, in study participants with spasticity due to stroke or CP. DESIGN:
      The study was a randomized, controlled, double-blind study with a cross-over
      design. SETTING: Participants were recruited from two rehabilitation clinics.
      Treatments were performed in participants' homes and all follow-ups were
      performed in the two rehabilitation clinics. POPULATION: Thirty-one participants
      were included in the study and 27 completed the study. Four participants
      discontinued the study. Two declined participation before baseline and two
      withdrew due to problems handling the garment. METHODS: Participants used the AT
      with and without electrical stimulation (active/non-active period) for six weeks
      each, followed by six weeks without treatment. Goal Attainment Scaling (GAS),
      change in mobility, arm-hand ability, spasticity and pain were measured at
      baseline and after 6, 12 and 18 weeks. RESULTS: Fifteen of the 27 participants
      fulfilled the treatment protocol in terms of recommended use. Deviations were
      frequent. No statistically significant differences in outcome were found between
      the active and the non-active treatment periods. During the active period, an
      improvement was seen in the 10-meter comfortable gait test, time and steps. An
      improvement was seen in both the active and non-active periods for the GAS.
      CONCLUSIONS: Compliance was low, partly due to deviations related to the garment,
      complicating the interpretation of the results. Further research should focus on
      identifying the target population and concomitant rehabilitation strategies.
      CLINICAL REHABILITATION IMPACT: The evaluated concept of multifocal
      transcutaneous electrical stimulation (TES) represents an interesting addition to
      the existing repertoire of treatments to alleviate muscle spasticity. The
      evaluated concept allows TES to be self-administered by the patient in the home
      environment. A more elaborate design of training activities directly related to
      patient's own rehabilitation goals is recommended and may increase the value of
      the evaluated concept.

PMID- 29072044
TI  - Comparison of the effect of focused and radial extracorporeal shock waves on
      spastic equinus in patients with stroke: a randomized controlled trial.
AB  - BACKGROUND: Recent studies have suggested that either focused or radial shock
      wave therapy is an effect method for the treatment of spasticity in patients with
      stroke. However, no previous study compared these two types of extracorporeal
      shock wave on spasticity in patients with stroke. This study aimed to compare the
      effect of focused and radial shock wave therapy for the treatment of spastic
      equinus in patients with stroke. DESIGN: Randomized control trial. SETTING:
      Outpatient rehabilitation center in a medical center. POPULATION: Thirty-two
      stroke patients with spastic equinus (18 males and 14 women; mean age, 60.1+/
      10.6 years). METHODS: Patients were randomly assigned to receive three sessions
      of either focused or radial shock wave therapy at 1-week intervals. The
      intensities that were used during focused shock wave therapy (0.12 mJ/mm2) and
      radial shock wave therapy (2.4 bar) were comparable. The patients were evaluated
      at baseline and at 1, 4, and 8 weeks after the final shockwave treatment. The
      primary outcome measure was change of modified Ashworth Scale Score of
      gastrocnemius muscle. The secondary outcome measures were Tardieu Scale, ankle
      passive range of motion, dynamic foot contact area and gait speed. A linear mixed
      model with repeated measures was used to compare each outcome measure between the
      two groups. RESULTS: Both groups improved significantly in terms of modified
      Ashworth Scale Score and Tardieu Scale, and no differences were found between the
      two groups. In terms of ankle passive range of motion and plantar contact area
      during gait, the radial shock wave therapy yielded a significantly greater
      improvement than the focused shock wave therapy. No significant changes were
      observed in gait speed in either group. CONCLUSIONS: Our study suggested that
      focused and radial shock wave therapy resulted in similar significant
      improvements in the modified Ashworth scale score and Tardieu scale, but those in
      the radial shock wave therapy group experienced greater improvements in the ankle
      passive range of motion and plantar contact area during gait. CLINICAL
      REHABILITATION IMPACT: Both focused and radial shock wave therapy yielded similar
      improve the spasticity of gastrocnemius muscle. Radial shock wave therapy is
      superior to focused shock wave therapy in terms of improving the ankle passive
      range of motion and plantar contact area during gait in patients with stroke.

PMID- 29072046
TI  - Diagnosis and clinical evaluation of neurogenic bladder.
AB  - Neurologic diseases lead to urinary dysfunctions. The aim of this article was to
      present an overview of diagnosis and evaluation of neurogenic bladder with a
      special focus on urodynamic tests. Overactive bladder, with high detrusor
      pressure associated with detrusor sphincter dyssynergia, can lead to severe
      complications with renal failure, upper urinary tract dilatation and infectious
      complications. Underactive bladder with voiding dysfunction and urinary
      retention, is also a risk factor of urological alterations. Full clinical
      examinations, including urodynamics and selective radiographic imaging studies,
      are essential to best manage these patients.

PMID- 29072045
TI  - Intradetrusor injection of botulinum toxin A and sacral neuromodulation for
      neurogenic detrusor overactivity.
AB  - Intradetrusor injection of botulinum toxin A and sacral neuromodulation are the
      two recommended third line treatments for patients with neurogenic detrusor
      overactivity, before undergoing with surgery. However, only Botox(r) injection is
      supported by a high level of evidence allowing its recommendation by all
      institutional guidelines. Despite few positive results, sacral neuromodulation
      should be proposed in carefully selected patients. Indeed, other studies remain
      mandatory to increase its level of evidence necessary for allowing its use in
      neurogenic detrusor overactivity.

PMID- 29072048
TI  - Cervical ripening and induction of labour: Inpatient or outpatient, oral
      misoprostol or Foley catheter?

PMID- 29072047
TI  - Estimating the hemodynamic influence of variable main body-to-iliac limb length
      ratios in aortic endografts.
AB  - BACKGROUND: We conducted a computational study to assess the hemodynamic impact
      of variant main body-to-iliac limb length (L1/L2) ratios on certain hemodynamic
      parameters acting on the endograft (EG) either on the normal bifurcated (Bif) or
      the cross-limb (Cx) fashion. METHODS: A customary bifurcated 3D model was
      computationally created and meshed using the commercially available ANSYS ICEM
      (Ansys Inc., Canonsburg, PA, USA) software. The total length of the EG, was kept
      constant, while the L1/L2 ratio ranged from 0.3 to 1.5 in the Bif and Cx
      reconstructed EG models. The compliance of the graft was modeled using a Fluid
      Structure Interaction method. Important hemodynamic parameters such as pressure
      drop along EG, wall shear stress (WSS) and helicity were calculated. RESULTS: The
      greatest pressure decrease across EG was calculated in the peak systolic phase.
      With increasing L1/L2 it was found that the Pressure Drop was increasing for the
      Cx configuration, while decreasing for the Bif. The greatest helicity (4.1 m/s2)
      was seen in peak systole of Cx with ratio of 1.5 whereas its greatest value (2
      m/s2) was met in peak systole in the Bif with the shortest L1/L2 ratio (0.3).
      Similarly, the maximum WSS value was highest (2.74Pa) in the peak systole for the
      1.5 L1/L2 of the Cx configuration, while the maximum WSS value equaled 2 Pa for
      all length ratios of the Bif modification (with the WSS found for L1/L2=0.3 being
      marginally higher). There was greater discrepancy in the WSS values for all L1/L2
      ratios of the Cx bifurcation compared to Bif. CONCLUSIONS: Different L1/L2
      rations are shown to have an impact on the pressure distribution along the entire
      EG while the length ratio predisposing to highest helicity or WSS values is also
      determined by the iliac limbs pattern of the EG. Since current custom-made EG
      solutions can reproduce variability in main-body/iliac limbs length ratios,
      further computational as well as clinical research is warranted to delineate and
      predict the hemodynamic and clinical effect of variable length ratios.

PMID- 29072049
TI  - Impact of the Z potential technique on reducing the sperm DNA fragmentation
      index, fertilization rate and embryo development.
AB  - BACKGROUND: In assisted reproduction procedures, we need to develop and enhance
      new protocols to optimize sperm selection. The aim of this study is to evaluate
      the ability of the Z potential technique to select sperm with intact DNA in non
      normospermic patients and evaluate the impact of this selection on embryonic
      development. METHODS: We analyzed a total of 174 human seminal samples with at
      least one altered parameter. We measured basal, post density gradients, and post
      density gradients + Z potential DNA fragmentation index. To evaluate the impact
      of this technique on embryo development, 54 cases were selected. The embryo
      development parameters evaluated were fertilization rate, cleavage rate, top
      quality embryos at the third day and blastocysts rate. RESULTS: We found
      significant differences in the study groups when we compared the sperm
      fragmentation index by adding the Z potential technique to density gradient
      selection vs. density gradients alone. Furthermore, there was no significant
      difference in the embryo development parameters between the low sperm
      fragmentation index group vs. the moderate and high sperm fragmentation index
      groups, when selecting sperms with this new technique. CONCLUSIONS: The Z
      potential technique is a very useful tool for sperm selection; it significantly
      reduces the DNA fragmentation index and improves the parameters of embryo
      development. This technique could be considered routine for its simplicity and
      low cost.

PMID- 29072051
TI  - Effects of 5 IU oxytocin bolus and 20 IU oxytocin infusion compared to 5 IU
      oxytocin bolus and normal saline infusion in the control of blood loss during and
      after ante-partum lower segment caesarean section: a randomized controlled trial
AB  - Introduction: Obstetric haemorrhage is the leading cause of maternal mortality
      worldwide and in most cases it relates to uterine atony. Even though an oxytocin
      bolus is used routinely, additional infusion of oxytocin may be required if
      haemorrhage occurs. Objectives: To compare the effects of 20 IU oxytocin infusion
      and 5 IU bolus with 5 IU bolus and 500ml normal saline on the control of blood
      loss in antepartum lower segment caesarean section. Methods: A double-blind
      randomized controlled trial was conducted in the Teaching Hospital, Peradeniya,
      Sri Lanka. Ninety two pregnant women, forty six from each group were randomized
      to receive either intravenous slow 5 IU oxytocin bolus over 1 minute and
      additional 20 IU oxytocin infusion in 500 ml of 0.9% saline solution over 4 hours
      (Group-A) or 5 IU oxytocin bolus over 1 minute and 500 ml of 0.9% Saline over 4
      hours (Group B). Visual assessment of mean blood loss was done by the surgeon and
      anaesthetist. Blood loss was calculated based on the body weight and haematocrit
      before and 48 hours after delivery. Results: Calculated mean blood loss (456.0ml
      vs 569.8ml) was significantly less in group A (p=0.046). Visual estimation of
      blood loss by surgeon (476.9 vs 552.1) (p=0.01) and anaesthetist (492.7 vs 557.2)
      (p= 0.03) were also significantly less in group A. Conclusions: Additional
      oxytocin infusion at antepartum caesarean section reduces blood loss during and
      after caesarean section significantly.

PMID- 29072050
TI  - Long Non Coding RNA Expression Intersecting Cancer and Spermatogenesis: A
      Systematic Review
AB  - Background: Numerous similarities have been noted between gametogenic and
      tumorigenic programs in featuressuch as global hypomethylation, immune evasion,
      immortalization, meiosis induction, and migration. In addition,
      aberrantexpression of testis specific genes has been detected in various cancers
      which has led to categorization of these genesas "cancer-testis genes". Most of
      the examples identified in this category are protein encoding. However, recent
      studieshave revealed that non-coding RNAs, including long non coding RNAs
      (lncRNAs), may have essential regulatoryroles in telomere biology, chromatin
      dynamics, modulation of gene expression and genome structural organization.All of
      these functions are implicated in both gametogenic and tumorigenic programs.
      Methods: In the present study,we conducted a computerized search of the
      MEDLINE/PUBMED and Embase databases with the key words lncRNA,gametogenesis,
      testis and cancer. Results: We found a number of lncRNAs with essential roles and
      notable expressionin both gametogenic and cancer tissues. Conclusions: Comparison
      between cancer tissues and gametogenic tissueshas shown that numerous lncRNAs are
      expressed in both, playing similar roles in processes modulated by
      signalingpathways such as Wnt/beta-catenin and PI3K/AKT/mTOR. Evaluation of
      expression patterns and functions of thesegenes should pave the way to discovery
      of biomarkers for early detection, prognostic assessment and evaluation
      oftherapeutic responses in cancers.

PMID- 29072052
TI  - Association between Polymorphisms of ERCC5 Gene and Susceptibility to Gastric
      Cancer: A Systematic Review and Meta-Analysis
AB  - Background: several epidemiological studies have suggested that polymorphisms of
      the Excision Repair CrossComplementing Group-5 (ERCC5) gene might be related to
      gastric cancer risk; however, the results have beeninconsistent or controversial.
      Therefore, we have performed a systematic review and meta-analysis to clarify
      theassociation between the ERCC5 gene polymorphisms and gastric cancer risk.
      Materials and Methods: An electronicsearch was conducted of several databases,
      including PubMed, Web of Science, and Google Scholar for articles thatdescribe
      the association between polymorphisms of the ERCC5 gene and susceptibility of
      gastric cancer. Results: Atotal of 33 case control studies in 15 publications
      were included in the present meta-analysis. There were significantassociations
      between gastric cancer susceptibility and ERCC5 gene rs751402 C>T (T vs. C: OR =
      1.166, 95%C = 1.066-1.274, p= 0.001; TT vs. CC: OR = 0.723, 95% CI = 0.587-0.890,
      p = 0.002; TT+TC vs. CC: OR = 0.853,95% CI = 0.757-0.961, p = 0.009; TT vs.
      TC+CC: OR = 0.793, 95% CI = 0.659-0.955, p = 0.015), rs2296147 T>C(C vs. T: OR =
      1.268, 95% C = 1.049-1.532, p= 0.014), rs873601 G>A polymorphisms (A vs. G, OR =
      1.087, 95%C = 1.021-1.159, p= 0.010; AA vs. GG, OR = 1.184, 95% CI = 1.043-1.343,
      p = 0.009, AA vs. AG+GG, OR = 1.156,95% CI = 1.040-1.284, p = 0.007), but not
      rs2094258 C>T and rs1047768 T>C. Conclusion: the current meta
      analysisdemonstrates that rs751402 C>T, rs2296147 T>C, and rs873601 G>A
      polymorphisms of ERCC5 gene are associatedwith the susceptibility of gastric
      cancer.

PMID- 29072054
TI  - The effect of thriphala, a herbal Ayurveda formulation, on serum lipids, in
      patients on a maintenance dose of atorvastatin for hyperlipidaemia: a randomized
      controlled trial
AB  - Introduction: Thriphala, a herbal medicinal formulation, is a bedrock of Ayurveda
      therapeutics with many postulated benefits. Objectives: We performed a clinical
      trial to test the effects of Swastha Thriphala(r), a proprietary preparation of
      thriphala, on serum lipid parameters in patients receiving atorvastatin. Methods:
      Consenting adults receiving a maintenance dose of atorvastatin 10mg (Atorlip(r))
      daily from a clinic of the Institute of Cardiology, National Hospital of Sri
      Lanka for lipid regulation, were randomly assigned, after counselling, to
      receiveeither the proprietary herbal medicinal product Swastha Thriphala(r)
      (Treatment Group, n= 101) or a placebo (Control Group n= 97), at the stipulated
      dose daily, for three calendar months. Results: In the treatment group (n=101)
      the addition of a proprietary preparation of thriphala formulated as caplets of
      Swastha Thriphala(r), in the standard daily dosage for three months, as an
      adjunct to atorvastatin 10mg, had a significant (p<0.0001) reduction in the mean
      total blood cholesterol, mean cholesterol/HDL ratio (p<0.0001), and mean non- HDL
      cholesterol (p<0.0001) when compared to the Control Group (n=97) receiving
      placebo caplets in the same daily dose, with atorvastatin 10mg, for the same
      period. In the Treatment Group mean HDL, LDL, HS-CRP, and triglyceride
      concentrations showed non-significant reductions, and nonsignificant elevations
      in the Control Group Conclusions: Swastha Thriphala(r) when used in the
      stipulated dosage as an adjunct to atorvastatin 10 mg daily, significantly
      enhances its cholesterol reducing action in patients. The use of Swastha
      Thriphala(r) as single therapy for lipid regulation, and the mode of its action
      deserve investigation.

PMID- 29072053
TI  - An Overview of Asbestos and Malignant Pleural Mesothelioma: An Iranian
      Perspective
AB  - Asbestos refers to a group of minerals that appears naturally in the environment
      as bundles of fibers. The incidencerate of asbestos-related diseases has
      considerably increased as well as the amount of asbestos utilization in few
      countries.Malignant pleural mesothelioma (MPM) is a rare type of aggressive and
      life threatening neoplasm which arise fromvarious serous surfaces: pleura,
      peritoneum, tunica vaginalis and pericardium. The first case of MPM was
      reportedin 1947. MPM etiologically is associated to the exposure of asbestos
      fibers. This form of malignancy is difficult todiagnose in paraclinical work-ups
      because mesothelioma could occur within 10-20 years of the first-time exposure
      toasbestos. The burden of MPM is not yet to be wholly understood. The toxic side
      effects of asbestos on environmentand people compelled the European countries to
      accept the French view upon this matter. However, this approach hasnot been
      accepted by some developing countries. This review provides a brief points and
      facts in relation to MPM andasbestos in Iran.

PMID- 29072055
TI  - Diagnostic Challenges in Prostate Cancer and 68Ga-PSMA PET Imaging: A Game
      Changer?
AB  - Prostate cancer (PC) is the most frequent solid tumor in men and the third most
      common cause of cancer mortalityamong men in developed countries. Current imaging
      modalities like ultrasound (US), computerized tomography (CT),magnetic resonance
      imaging (MRI) and choline based positron emission (PET) tracing have
      disappointing sensitivity fordetection of nodal metastasis and small tumor
      recurrence. This poses a diagnostic challenge in staging of intermediateto high
      risk PC and restaging of patients with biochemical recurrence (PSA >0.2 ng/ml).
      Gallium-68 labeled prostatespecific membrane antigen (68Ga-PSMA) PET imaging has
      now emerged with a higher diagnostic yield. 68Ga-PSMAPET/CT or PET/MRI can be
      expected to offer a one-stop-shop for staging and restaging of PC. PSMA ligands
      labeledwith alpha and beta emitters have also shown promising therapeutic
      efficacy for nodal, bone and visceral metastasis.Therefore a PSMA based
      theranostics approach for detection, staging, treatment, and follow-up of PC
      would appearto be highly valuable to achieve personalized PC treatment.

PMID- 29072056
TI  - A Systems Biology Approach Provides Deeper Insights into Differentially Expressed
      Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
AB  - Objective: To date, numerous studies have been conducted to search for reasons
      for chemoresistance anddifferences in survival rates of patients receiving
      chemotherapy. We have sought to identify differentially expressedgenes (DEGs)
      between predicted chemotherapy resistance and sensitive phenotypes by a network
      as well as geneenrichment approach. Methods: Functional modules were explored
      with network analysis of DEGs in predictedneoadjuvant taxane-anthracycline
      resistance versus sensitive cases in the GSE25066 dataset, including 508 samples.
      Alinear model was created by limma package in R to establish DEGs. Results: A
      gene set related to phagocytic vesiclemembrane was found to be up-regulated in
      chemoresistance samples. Also, we found GO_CYTOKINE_ACTIVITYand GO_GROWTH_FACTOR
      BINDING to be up-regulated gene sets with the chemoresistance phenotype.
      Growthfactors and cytokines are two groups of agents that induce the immune
      system to recruit APCs and promote tolerogenicphagocytosis. Some hub nodes like
      S100A8 were found to be important in the chemoresistant tumor cell network
      withassociated high rank genes in GSEA. Conclusions: Functional gene sets and hub
      nodes could be considered as potentialtreatment targets. Moreover, by screening
      and enrichment analysis of a chemoresistance network, ligands and chemicalagents
      have been found that could modify significant gene sets like the phagocytic
      vesicle membrane functional geneset as a key to chemoresistance. They could also
      impact on down- or up-regulated hub nodes.

PMID- 29072057
TI  - Nepalese Helicobacter pylori Genotypes Reflects a Geographical Diversity than a
      True Virulence Factor
AB  - Background: The data about the association between Helicobacter pylori putative
      virulence factors; iceA andjhp0562/beta-(1,3)galT with clinical outcomes are
      still controversial. We identified and analyzed two putative H. pylorivirulence
      factors in Nepalese strains. Methods: The iceA and jhp0562/beta-(1,3)galT allelic
      types were determined bypolymerase chain reaction amplification. Histological
      analysis were classified according to the updated Sydney systemand the Operative
      Link on Gastritis Assessment (OLGA) system. Results: Among 49 strains, iceA1
      negative/iceA2positive (iceA2-positive) was predominant type (57.1%, 28/49) and
      20 (40.8%) were iceA1 positive/iceA2 negative. Theremaining one (2.0%) was
      positive for both iceA1 and iceA2 (iceA1/iceA2-mixed). Patients infected with
      iceA1-positivestrains tended to be higher OLGA score than iceA2-positive strains
      [1.45 [1] vs. 0.07 [0.5], P = 0.09, respectively).The jhp0562 negative/beta
      (1,3)galT positive was predominant type (25/51, 49.0%), followed by double
      positive forjhp0562/beta-(1,3)galT (15/51, 29.4%) and jhp0562 positive/beta
      (1,3)galT negative (11/51, 21.6%). Activity in the corpuswas significantly higher
      in jhp0562 negative/beta-(1,3)galT positive than double positive of jhp0562/beta
      (1,3)galT positive[mean (median); 1.24 (1) vs. 0.73 (1), P = 0.03]. There was
      association between iceA and subtype of vacA signal region(e.g., s1a, s1b or s1c)
      and combination subtypes of signal and middle regions (e.g., s1a-m1c) (P = 0.02,
      r = 0.29; andP = 0.002, r = 0.42, respectively). In addition, jhp0562/beta
      (1,3)galT genotypes associated with cagA pre-EPIYA type(e.g., 6 bp-, 18 bp-, or
      no deletion-type) (P = 0.047, r = 0.15). Conclusion: The inconsistency results of
      the associationbetween iceA, jhp0562/beta-(1,3)galT and histological scores
      suggesting that these genes may associate with geneticheterogeneity rather than
      as a true virulence factor.

PMID- 29072058
TI  - p16INK4a Expression in Cervical Lesions Correlates with Histologic Grading - a
      Tertiary Level Medical Facility Based Retrospective Study
AB  - p16INK4a is a tumor-suppressor protein and cyclin-dependent kinase (cdk)
      inhibitor that blocks cdk4- andcdk6-mediated pRb phosphorylation to inhibit E2F
      dependent transcription and cell-cycle progression. Because the E7protein of high
      risk HPVs inactivates pRB, the resulting overexpression of p16INK4a may be a good
      marker for infectionwith high risk HPV types. Immunostaining of p16INK4a allows
      precise identification of even small CIN or cervicalcancer lesions in biopsy
      sections and can help reduce inter-observer variation in the histopathological
      interpretationof cervical biopsy specimens. The aims of the present study were to
      evaluate the expression of p16 INK4a in cervicalbiopsies and to compare the grade
      of cervical neoplasia with intensity of staining. The study covered 110
      cervicalbiopsy tissue blocks over a period of 2 years, (85 cases of CIN of
      varying grade and invasive cervical cancers and 25of non-neoplastic lesions).
      Immunostaining with p16INK4a antibodies followed standard operating procedures.
      Theresults showed an increasing trend for p16INK4a immunoreactivity from benign
      to higher grade lesions. Out of 25cases of non dysplasia (15 cervicitis &10
      immature squamous metaplasia), 8%(2/25) showed P16INK4a expression(grade 1).
      Among low grade lesions like CIN1, 32% (8/25) cases demonstrated P16INK4a
      expression (grade 1). Some52.3% (11/21) of CIN2 cases proved positive. The
      intensity of p16INK4a expression in CIN 2 was grade 1 in 33%,grade 2 in 14% and
      grade 3 in 4.7% of cases. All the CIN3 lesions and cervical squamous cell
      carcinomas exhibitedgrade 3 anti p16INK4a antibody staining. The association of
      p16INK4a expression with histologic grade of cervicalpathology was highly
      significant (chi2-value:51.81, p<0.0001). The staining intensity increase with
      higher grade diseasewas also statistically significant (chi2-value :133.95,
      p<0.0001).

PMID- 29072059
TI  - Body Misperception and Its Associated Factors among Cancer Survivors in Korea
AB  - Background: As the number of cancer survivors is increasing, the importance of
      their healthcare managementis becoming emphasized. For this purpose, appropriate
      recognition of the importance of body weight is necessary.This study concerned
      misconceptions about body weight and related factors among cancer patients.
      Methods: Thiscross-sectional study involved 1,159 participants who participated
      in the 2007-2012 Korean National Health andNutrition Examination Survey. Self
      reported questionnaires were used to assess cancer information,
      socioeconomicstatus, health behavior, and psychological factors. Results: Men had
      a higher rate of underestimation and a lower rateof overestimation of body weight
      than women (34.7% vs. 22.9%; 10.9% vs. 15.5%, respectively). Underestimation
      ofbody weight was positively associated with a self-assessment of being in poor
      health in men (OR 2.44, 95% CI 1.58-3.75) and in elderly women (OR 3.70, 95% CI
      2.44-5.23). Overestimation of body weight was positively associatedwith
      depression in men (OR 2.17, 95% CI 1.01-4.63) and a high educational level/high
      income level and having triedto control weight in women (OR 1.92, 95% CI 1.16
      3.18; OR 1.57, 95% CI 1.00-2.47; OR 3.24, 95% CI 1.82-5.77,respectively).
      Conclusions: Higher socioeconomic status (SES), depression, self-rated health
      status, age, and weightcontrol trials were found to be associated with
      underestimation and overestimation of body weight in cancer survivors.From this
      study, it is evident that more efforts are needed to remove misperceptions and to
      develop healthy behaviorfor cancer survivors by various means.

PMID- 29072060
TI  - Risk Factors for Hydatidiform Mole: Is Husband's Job a Major Risk Factor?
AB  - Background: The hydatidiform mole (HM) is a precancerous placenta considered as a
      gestational trophoblasticdisease (GTD). It may convert to more invasive forms of
      gestational trophoblastic neoplasia (GTN), endangering women'shealth by more
      severe complications. Most GTN cases originate from HM, which is associated with
      uterine bleeding,preeclampsia and thyroid problems. Its etiology has not been
      adequately explored, but some risk factors have beenreported. The aim of the
      present study was to assess any relationships between molar pregnancy and factors
      includingmothers' and husbands' occupations. Methods: In this case control study,
      seventy complete molar pregnancies (cases)were compared with 200 normal
      pregnancies (controls) in 5 educational hospitals affiliated to medical
      universitiesin Tehran, Iran. Data were analyzed using t-test, chi-square test,
      Fisher's exact test and logistic regression modeling.Results: There was no
      significant relationship between the risk of molar pregnancy and age, education,
      blood RH,parity, duration of OCP use, intra-uterine device usage, smoking,
      consanguinity of woman and husband, ethnicity,history of infertility, history of
      moles in the family, and dwelling ownership. The two groups were statistically
      differentregarding husbands' jobs, history of abortion, use OCP, and ABO blood
      group. The odds ratio with a husband's physicaljob having exposure to dust and
      soil was 18.2 (CI: 8.26-43.03, PV?0.001). Logistic regression analysis only
      showedhusband's job and husband's physical job exposure to dust and soil as
      predictors. Conclusion: Husband's jobs andespecially exposure to dust and soil
      could be a major risk factor for molar pregnancy. More studies on the
      epidemiology,occupational health, microbiology and genetics are warranted to shed
      more light on this abnormal pregnancy.

PMID- 29072061
TI  - When is compassionate appropriate for end-stage aortic valve stenosis?

PMID- 29072062
TI  - Morpho-functional cardiovascular adaptation in hypertensive patients: two
      dimensional speckle tracking echocardiographic study.
AB  - BACKGROUND: Twenty-four-hour blood pressure (BP) variability is an important
      predictor of organ damage and cardiovascular events. Although epidemiological
      data are widely based on evaluation of office (clinic) BP, 24-hour ambulatory BP
      monitoring (ABPM) accurately assess the severity of hypertension to predict
      cardiovascular events in hypertensive patients, because it more accurately
      reflects BP load on heart and blood vessels. Conventional transthoracic
      echocardiography (TTE), such as M-mode and two-dimensional (2D), and more
      advanced techniques, such as tissue Doppler imaging (TDI) and speckle tracking
      echocardiography (STE), are used to identify pathological changes of the
      hypertensive heart disease. In addition, the study of systemic arterial
      compliance (SAC) predicts the impact of the arterial stiffness on the LV
      remodeling. METHODS: Fifty-eight patients (34 males and 24 females, aged 53+/-12
      years) with hypertension for at least one year were studied using Ambulatory
      Blood Pressure Monitoring (ABPM), with evaluation of 24-hour, day time, night
      time and sleep and awake average systolic and diastolic BP, and subsequently with
      TTE, to evaluate the influence of the 24-hour average BP, integrated with
      echocardiographic parameters, on cardiovascular adaptations in hypertensive
      patients. ECHO parameters examined were: left ventricle (LV) mass indexed to body
      surface area (LVMi), LV ejection fraction (EF), left atrial volume indexed to
      body surface area (LAVi), mitral inflow velocities (E, A and E/A), mitral annulus
      velocities (S' and E') and E/E' ratio by TDI, LV global longitudinal strain (GLS)
      using 2D STE. SAC was derived by the ratio SVi/PP, using echocardiographic stroke
      volume index to body surface area (SVi) and pulse pressure (PP). RESULTS: LVMi
      showed a correlation with the 24-hour average BP (SBP r=0.32; DBP r=0.26), SBPd
      (r=0.32), DBPd (r=0.28) and SBPn (r=0.29). GLS was correlated with the 24-hour
      average BP (SBP r=0.30; DBP r=0.32), SBPd (r=0.32), DBPd (r=0.32) and with LVMi
      (r=0.42), LAVi with 24 hour SBP (r=0.28), while SAC with LVMi (r=0.29) and LAVi
      (r=0.33). CONCLUSIONS: ABPM and TTE evaluation can be particularly useful in
      hypertensive patients, even with normal office BP, to highlight the influence of
      24-hour blood pressure profile on LVM, and to a lesser extent, on LAV. SAC,
      instead, seems to be correlated both to LVM and LAV, independently of BP levels.

PMID- 29072063
TI  - Conscious sedation during cryoballoon ablation of atrial fibrillation: a
      feasibility and safety study.
AB  - BACKGROUND: Cryoballoon ablation for atrial fibrillation (cryoAF) is relatively
      simple, cost-effective and easy procedure. However, general anesthesia during
      this procedure may have negative impact on patients' mortality and morbidity, as
      well as procedure costs. We sought to assess the feasibility and safety of
      conscious sedation during cryoAF. METHODS: Patients with paroxysmal or
      persistent, drug-refractory AF who underwent a first procedure of cryoAF were
      included in our single-center, retrospective study. The loading dose of midazolam
      was 2 mg and loading fentanyl dose was 25 ug intravenously. Additional doses of
      midazolam and fentanyl were administered, if necessary. Midazolam and fentanyl
      were administered to maintain amnesia and analgesia, and patients' responsiveness
      in Ramsay Sedation Score was assessed every 10 minutes with sedation kept at the
      Ramsey Sedation Scale not exceeding Ramsey 3 Grade. RESULTS: A total of 71
      patients with mean age 59.5+/-11.1 years were enrolled (48 males, 68%). The TEE
      and the TEE-guided transseptal puncture was feasible in all patients. The mean
      duration of cryoAF procedure was 136.3+/-36.0 minutes. The overall mean midazolam
      and fentanyl used doses were: 5.1+/-3.1 mg (55.7+/-35.1 ug/kg) and 98.9+/-51.1 ug
      (1.13+/-0.60 ug/kg). In 3 patients (4.2%), vascular complications occurred
      (femoral vein bleeding with hematoma formation without communication with femoral
      artery). In 1 case (1.4%) transient right phrenic palsy was observed; symptoms
      disappeared completely within 12 hours after procedure. The overall acute
      procedural success rate of cryoAF (defined as electrical isolation of all
      pulmonary veins) was 68/71 (95.8%). CONCLUSIONS: Conscious sedation is a safe,
      efficacious and feasible during cryoablation of pulmonary veins for AF.

PMID- 29072064
TI  - Transcatheter aortic valve implantation (TAVI) in 2018: recent advances and
      future development.
AB  - Transcather aortic valve implantation (TAVI) has become a safe and indispensable
      treatment option for patients with severe symptomatic aortic stenosis (AS) who
      are at high or prohibitive surgical risk. In the past years, outcomes after TAVI
      have improved significantly and TAVI has emerged as a qualified alternative to
      surgical aortic valve replacement (SAVR) in the treatment of intermediate risk
      patients. Besides optimized patient screening, advanced imaging and increased
      examiner experience, transcatheter heart valve (THV) design addressed several key
      issues like vascular complications, pacemaker implantation and paravalvular
      leakage rates and improved considerably over time. Currently, several trials are
      investigating the role of TAVI in low surgical risk patients, novel indications
      and peri-operative management. In this review we give an overview on 1) current
      generation TAVI devices; on 2) recent clinical trial results and guidelines; and
      on 3) future trends and novel developments in the field of interventional
      treatment of AS.

PMID- 29072065
TI  - Freeway paclitaxel-releasing balloons to treat recurrent stenosis of
      arteriovenous fistula in hemodialysis patients.
AB  - BACKGROUND: To evaluate early and mid-term outcomes of Freeway paclitaxel
      releasing balloons (Eurocor GmbH, Bonn, Germany) in hemodialysis patients with
      recurrent stenosis of arteriovenous fistula. METHODS: Between July 2013 and
      December 2016 27 hemodialysis patients with recurrent stenosis of arteriovenous
      fistula underwent endovascular treatment with a Freeway balloon. About inclusion
      criteria, all patients were previously treated at the target lesion with a
      standard balloon angioplasty (BA). The intervals in months between standard BA
      and procedure with DCB (time BA-DCB) and between procedure with DCB and new
      restenosis (time DCB-restenosis) were evaluated and compared with T-test. 2-year
      estimated outcomes in terms of survival, primary patency, primary assisted
      patency, secondary patency, and freedom from target lesion restenosis (TLR) were
      assessed with Kaplan-Meier curves. RESULTS: Technical success was obtained in
      96.3% of the cases. During the follow-up (mean duration 13.6 months, range 1-33)
      13 patients (48.1%) had a new restenosis. Mean time BA-DCB was 4.8 months, and
      the mean time DCB-restenosis was 7.6 months with a statistically significant
      difference at T-test (P<0.001). Estimated 2-year rates of primary patency,
      primary assisted patency, secondary patency, and freedom from TLR were 31.8%,
      76.4%, 90.5%, and 30.2%, respectively. CONCLUSIONS: In our experience Freeway
      paclitaxel-releasing balloons were effective in the treatment of recurrent
      stenosis in hemodialysis patients previously treated with standard BA. At follow
      up about half of patients had no new target lesion restenosis and the time to a
      new restenosis was much longer compared to recurrence of stenosis after standard
      BA.

PMID- 29072066
TI  - Breast Cancer Screening Disparity among Korean American Immigrant Women in
      Midwest
AB  - Purpose: Using three breast cancer screening methods such as mammogram, Clinical
      Breast Examination (CBE),and Breast Self-Examination (BSE), this study
      investigated breast cancer screening rates and its associated factorsin Korean
      American immigrant women. Method: Cross-sectional data were obtained from 168
      Korean immigrantwomen aged 40 and older in Midwest. The Andersen's Behavioral
      Model (1995) theoretically guided this study andlogistic regression was used to
      examine factors associated with screening receipt and performance. Results:
      Studyparticipants reported low screening rates, specifically mammography and CBE
      uptake. About 71% of the women hada mammography at least once in their lifetime,
      while about 36% indicating receipt of a mammogram in the last threeyears. About
      59% of the women received a CBE at least once in their lifetime, while about 32%
      had CBE in the pastthree years. About 74% of study participants have performed
      BSE at least once in their life time, while about 68% havedone it in the past
      three years. Knowledge of screening method was consistently correlated with
      participant's threebreast cancer screening uptake. Additional factors that were
      positively associated with screening included older age,low barriers to
      mammograms, and lower educational attainment. Conclusions: Overall, study
      participants reportedlow rates of breast cancer screening receipt and
      performance. It is required to promote screening uptake among Koreanimmigrant
      women, especially women with young age, a lower level of education, and lack of
      health accessibility. Acommunity-based language-appropriate health education
      program should be developed to increase health care access.

PMID- 29072067
TI  - Stage Association of Preoperative Serum Carcinoembryonic Antigen with Gastric
      Adenocarcinoma in Iranian Patients
AB  - Background: Gastric cancer is the second leading cause of cancer-related
      mortality and the fourth most commoncancer globally. Tumor markers are needed for
      appropriate management and monitoring of treatment to improvequality of life.
      Recently, carcinoembryonic antigen (CEA) has been widely used as a tumor marker
      in the diagnosisand follow-up of some malignancies. The aim of this study was to
      evaluate the significance of CEA detection in thecourse of disease in gastric
      cancer patients at different stages. Methods: Seventy six cases of gastric
      adenocarcinomafrom the Rasht Razi Hospital were studied between January 2016 and
      December 2016, along with a control groupof 152 people. Serum CEA was measured by
      ELISA reader. Statistical analysis was performed using SPSS 14.0 forWindows (SPSS
      Inc., Chicago, USA). The two groups were also compared by cross-table analysis
      using Pearson'schi-square test, with P-values <0.05 considered significant.
      Results: CEA was positive in 61.8 % of patients versus2.6% of the control group
      (P = 0.0001). Some 21% of patients at stages I and II (initial disease) and 40.8%
      at stagesIII and IV (advanced disease) demonstrated positive CEA. which was
      significantly correlated with higher N stage andpoor differentiation.
      Conclusions: Our study showed that a high preoperative CEA level was not
      prevalent in earlystage gastric cancer patients. We recommend to design other
      prospective studies and meta-analyses for elucidation ofclaims for diagnostic
      efficacy.

PMID- 29072068
TI  - Cu Microbelt Network Embedded in Colorless Polyimide Substrate: Flexible Heater
      Platform with High Optical Transparency and Superior Mechanical Stability.
AB  - Metal nanowires have been considered as essential components for flexible
      transparent conducting electrodes (TCEs) with high transparency and low sheet
      resistance. However, large surface roughness and high interwire junction
      resistance limit the practical use of metal wires as TCEs. Here, we report Cu
      microbelt network (Cu MBN) with coalescence junction and low surface roughness
      for next-generation flexible TCEs. In particular, the unique embedded structure
      of Cu MBN in colorless polyimide (cPI) film was achieved to reduce the surface
      roughness as well as enhance mechanical stability. The TCEs using junction-free
      Cu MBN embedded in cPI exhibited excellent mechanical stability up to 100 000
      bending cycles, high transparency of 95.18%, and a low sheet resistance of 6.25
      Omega sq-1. Highly robust Cu MBN-embedded cPI-based TCE showed outstanding
      flexible heater performance, i.e., high saturation temperature (120  degrees C)
      at very low voltage (2.3 V), owing to the high thermal stability of cPI and
      excellent thermal conductivity of the Cu MBN.

PMID- 29072069
TI  - A Multiheteroatom [3,3]-Sigmatropic Rearrangement: Disproportionative Entries
      into 2-(N-Heteroaryl)methyl Phosphates and alpha-Keto Phosphates.
AB  - A novel multiheteroatom (N, O and P) [3,3]-sigmatropic rearrangement is
      disclosed, based on two important types of organophosphates, 2-(N-heteroaryl)
      methyl phosphates and alpha-keto phosphates, being accessed smoothly and
      efficiently.

PMID- 29072070
TI  - High-Sensitivity Electrochemiluminescence Probe with Molybdenum Carbides as
      Nanocarriers for alpha-Fetoprotein Sensing.
AB  - Suitably designed electrochemiluminescence (ECL) carrying group acting as high
      efficiency solid-state probe has attracted a lot of attention. Herein, molybdenum
      carbides with the two-dimensional ultrathin nanosheet structure on the surface
      and excellent conductivity were successfully employed as the nanocarriers for the
      capture of ECL reagent of luminol-capped Au nanoparticles (luminol-AuNPs).
      Notably, the luminol-AuNPs in the hybrid (luminol-AuNPs@Mo2C) exhibited enhanced
      ECL performance (~6-fold) as compared to individual luminol-AuNPs because of the
      facilitated electron transfer process. Ultimately, the as-prepared ECL label was
      used to construct a label-free ECL immunosensor for the detection of alpha
      fetoprotein (AFP). The immunosensor shows high selectivity and high sensitivity
      to AFP detection with a wide linear range of 0.1 pg.mL-1 to 30 ng.mL-1 and an
      extremely low detection limit of 0.03 pg.mL-1 (S/N = 3). Moreover, the fabricated
      ECL immunosensor exhibit satisfied performance in the practical application. This
      novel sensing strategy not only broadens the application of molybdenum carbides
      but also provides a new efficient approach to detect various biomolecules.

PMID- 29072072
TI  - Acemannan and Fructans from Aloe vera (Aloe barbadensis Miller) Plants as Novel
      Prebiotics.
AB  - The nutraceutical properties of Aloe vera have been attributed to a glucomannan
      known as acemannan. Recently information has been published about the presence of
      fructans in Aloe vera but there are no publications about acemannan and fructans
      as prebiotic compounds. This study investigated in vitro the prebiotic properties
      of these polysaccharides. Our results demonstrated that fructans from Aloe vera
      induced bacterial growth better than inulin (commercial FOS). Acemannan
      stimulated bacterial growth less than fructans, and as much as commercial FOS.
      Using qPCR to study the bacterial population of human feces fermented in a
      bioreactor simulating colon conditions, we found that fructans induce an increase
      in the population of Bifidobacterium spp. Fructans produced greater amounts of
      short chain fatty acids (SCFA), while the branched-chain fatty acids (BCFA) did
      not increase with these polysaccharides. Acemannan increased significantly
      acetate concentrations. Therefore, both Aloe vera polysaccharides have prebiotic
      potentials.

PMID- 29072071
TI  - Extending roGFP Emission via Forster-Type Resonance Energy Transfer Relay Enables
      Simultaneous Dual Compartment Ratiometric Redox Imaging in Live Cells.
AB  - Reactive oxygen species (ROS) mediate both intercellular and intraorganellar
      signaling, and ROS propagate oxidative stress between cellular compartments such
      as mitochondria and the cytosol. Each cellular compartment contains its own
      sources of ROS as well as antioxidant mechanisms, which contribute to dynamic
      fluctuations in ROS levels that occur during signaling, metabolism, and stress.
      However, the coupling of redox dynamics between cellular compartments has not
      been well studied because of the lack of available sensors to simultaneously
      measure more than one subcellular compartment in the same cell. Currently, the
      redox-sensitive green fluorescent protein, roGFP, has been used extensively to
      study compartment-specific redox dynamics because it provides a quantitative
      ratiometric readout and it is amenable to subcellular targeting as a genetically
      encoded sensor. Here, we report a new family of genetically encoded fluorescent
      protein sensors that extend the fluorescence emission of roGFP via Forster-type
      resonance energy transfer to an acceptor red fluorescent protein for dual-color
      live-cell microscopy. We characterize the redox and optical properties of the
      sensor proteins, and we demonstrate that they can be used to simultaneously
      measure cytosolic and mitochondrial ROS in living cells. Furthermore, we use
      these sensors to reveal cell-to-cell heterogeneity in redox coupling between the
      cytosol and mitochondria when neuroblastoma cells are exposed to reductive and
      metabolic stresses.

PMID- 29072073
TI  - Sequence-Based Prediction of Cysteine Reactivity Using Machine Learning.
AB  - As one of the most intrinsically reactive amino acids, cysteine carries a variety
      of important biochemical functions, including catalysis and redox regulation.
      Discovery and characterization of cysteines with heightened reactivity will help
      annotate protein functions. Chemical proteomic methods have been used to
      quantitatively profile cysteine reactivity in native proteomes, showing a strong
      correlation between the chemical reactivity of a cysteine and its functionality;
      however, the relationship between the cysteine reactivity and its local sequence
      has not yet been systematically explored. Herein, we report a machine learning
      method, sbPCR (sequence-based prediction of cysteine reactivity), which combines
      the basic local alignment search tool, truncated composition of k-spaced amino
      acid pair analysis, and support vector machine to predict cysteines with hyper
      reactivity based on only local sequence features. Using a benchmark set compiled
      from hyper-reactive cysteines in human proteomes, our method can achieve a
      prediction accuracy of 98%, a precision of 95%, and a recall ratio of 89%. We
      utilized these governing features of local sequence motifs to expand the
      prediction to potential hyper-reactive cysteines in other proteomes deposited in
      the UniProt database. We validated our predictions in Escherichia coli by
      activity-based protein profiling and discovered a hyper-reactive cysteine from a
      functionally uncharacterized protein, YecH. Biochemical analysis suggests that
      the hyper-reactive cysteine might be involved in metal binding. Our computational
      method provides a large inventory of potential hyper-reactive cysteines in
      proteomes and is highly complementary to other experimental approaches to guide
      systematic annotation of protein functions in the postgenome era.

PMID- 29072074
TI  - High-Temperature Current Collection Enabled by the in Situ Phase Transformation
      of Cobalt-Nickel Foam for Solid Oxide Fuel Cells.
AB  - For the commercial development of solid oxide fuel cells (SOFCs), cathode current
      collection has been one of the most challenging issues because it is extremely
      difficult to form continuous electric paths between two rigid components in a
      high-temperature oxidizing atmosphere. Herein, we present a Co-Ni foam as an
      innovative cathode current collector that fulfills all strict thermochemical and
      thermomechanical requirements for use in SOFCs. The Co-Ni foam is originally in
      the form of a metal alloy, offering excellent mechanical properties and
      manufacturing tolerance during stack assembly and startup processes. Then, it is
      converted to the conductive spinel oxide in situ during operation and provides
      nearly ideal structural and chemical characteristics as a current collector, gas
      distributor, and load-bearing component. The functionality and durability of the
      Co-Ni foam are verified by unit cell test and 1 kW-class stack operation,
      demonstrating performance that is equivalent to that of precious metals as well
      as an exceptional stability under dynamic conditions with severe temperature and
      current variations. This work highlights a cost-effective technique to achieve
      highly reliable electric contacts over the large area using the in situ metal-to
      ceramic phase transformation that could be applied to various high-temperature
      electrochemical devices.

PMID- 29072075
TI  - CO2 and Redox Dual Responsive Pickering Emulsion.
AB  - Herein, we described for the first time a CO2 and redox dual responsive paraffin
      oil-in-water Pickering emulsion stabilized by the modified silica nanoparticles
      with Se-containing tertiary amine, SeTA, in which the tertiary amine serves as a
      CO2-sensitive group, and the Se atom serves as a redox-sensitive center. The
      Pickering emulsion can be reversibly switched between stable and unstable states
      by bubbling CO2 and N2 in the reduced state, or with the addition of H2O2 and
      Na2SO3 in the absence of CO2, because of the adsorption and desorption of SeTA on
      the silica surface. The former is mainly attributed to a CO2-controllable
      electrostatic attraction, resulting from the transition of molecules between
      cationic and nonionic states; whereas, the latter is ascribed to a redox-tunable
      hydrogen bonding, originating from the transition of molecules between selenide
      and selenoxide. However, in the presence of CO2, redox can only induce a change
      in the droplet size, not demulsification. These interesting and unique
      multiresponsive behaviors endow the Pickering emulsion with a capacity for
      intelligent control of emulsification and demulsification, as well as the droplet
      size, which may be an asset for a myriad of technological applications in
      biomedicine, microfluidics, drug delivery, and cosmetics.

PMID- 29072076
TI  - Nucleo-Palladation-Triggering Alkene Functionalization: A Route to gamma
      Lactones.
AB  - An unprecedented strategy for the highly effective synthesis of gamma-lactones
      from homoallylic alcohols was achieved by palladium catalysis in one step. The
      protocol affords aryl, alkyl, and spiro gamma-lactones directly from readily
      available homoallylic alcohols in good yields with excellent functional group
      tolerance and high chemoselectivity under mild conditions.

PMID- 29072077
TI  - Activation and Substitution of 1-Ferrocenylalkylamines with Allenones:
      Application to Three-Component Synthesis of 4-(1-Ferrocenylalkyl)pyrazoles.
AB  - A one-pot, two-step three-component synthesis of 4-(1-ferrocenylalkyl)pyrazoles
      has been developed involving activation and substitution of 1
      ferrocenylalkylamines with allenones under mild conditions. A range of 1
      ferrocenylalkylamines reacted with allenones in the presence of dipicolinic acid
      at room temperature without extrusion of air and moisture, and the resulting
      crude products were treated with hydrazine to afford structurally diverse 4-(1
      ferrocenylalkyl)pyrazoles in moderate to good yields. Moreover, the three
      component reaction was successfully extended to an enantioenriched alpha
      ferrocenylbenzylamine with complete retention of configuration.

PMID- 29072078
TI  - Integrated Multifunctional Electrochemistry Microchip for Highly Efficient
      Capture, Release, Lysis, and Analysis of Circulating Tumor Cells.
AB  - The circulating tumor cells (CTCs) in the blood allow the noninvasive analysis of
      metastatic mechanisms, cancer diagnosis, prognosis, disease monitoring, and
      precise therapy through "liquid biopsies". However, there is no integrated and
      robust multifunctional microchip, which not only could highly efficient capture
      CTCs, but also fast release and lyse cells on one single chip without using other
      biochemical agents for downstream biomedical analysis. In this work, we
      integrated the three functions in one electrochemical microchip (echip) by
      intentionally designing a cactus-like, topologically structured conductive array
      consisted of a PDMS micropillar-array core and an electroconductive gold coating
      layer with hierarchical structure. The echip presented a capture efficiency of 85
      100% for different cell lines in both buffer solution and whole blood. Moreover,
      the validity of the echip was further evaluated by using non-small-cell lung
      cancer patient samples. The electrochemical released cells or lysed-cell
      solutions could be obtained within 10 min and have been successfully used for
      mutant detection by DNA sequencing or RT-PCR. The fast release at a relative low
      voltage (-1.2 V) was originating from an electrochemical cleavage of the Au-S
      bonds that immobilized antibody on the chip. The electrochemical lysis took place
      at a high voltage (20 V) with an admirable performance. Thus, the highly
      integrated multifunctional echip was well demonstrated and promised a significant
      application in the clinical field.

PMID- 29072079
TI  - The endoscopic ultrasound-assisted Rendez-Vous technique for treatment of
      recurrent pancreatitis due to pancreas divisum and ansa pancreatica.
AB  - Endoscopic treatment of pancreatic ductal malformations causing recurrent acute
      pancreatitis, such as pancreas divisum or ansa pancreatica, is mainly based on
      the sphincterotomy of the minor papilla. However, the technical complexity of
      conventional endoscopic retrograde cholangiopancreatography (ERCP) is increased
      in patients presenting anatomical variants like these and it may be unsuccessful.
      We report the case of a pancreas divisum combined with ansa pancreatica and
      describe the cannulation and sphincterotomy of the minor papilla using an
      ultrasound-assisted Rendez-Vous technique.

PMID- 29072080
TI  - GETTEMO position statement on bariatric endoscopic techniques as a voluntary
      medicine.
AB  - Dear Editor, We would like to clarify certain points in the article by C. Dolz et
      al. entitled "Informed consent in digestive endoscopy - Patient information,
      endoscopist protection", more specifically regarding the section "Obesity
      treatments". First, we want to congratulate the authors for their highly relevant
      yearlong research of the medico-legal aspects of Spanish endoscopy and for
      sharing their knowledge with endoscopists on a national level. With regard to the
      endoscopic management of obesity, we consider that the informed consent process
      should be even more comprehensive than that with other endoscopic techniques. As
      the author highlighted, there is less experience in some of these techniques.

PMID- 29072081
TI  - Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta
      analysis of case series.
AB  - Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine
      tumors. The aim of this study is to analyze the phenotype and biologic behavior
      of resected cystic neuroendocrine tumors. A systematic review and meta-analysis
      were conducted until September 2016 using a search in Medline, Scopus, and EMBASE
      with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and
      "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting
      on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n
      = 40) corresponded to multiple endocrine neoplasia endocrine type 1. Were
      diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity
      of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional
      tumors, insulinoma was the most frequent. According to the European
      Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb),
      and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I
      IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly
      lower (p = 0.0001) in functional tumors. In patients with multiple endocrine
      neoplasia there was a higher incidence of functional (62.5%) and multifocal
      (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic
      pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are
      different to those of solid neuroendocrine tumors.

PMID- 29072082
TI  - Chemoprevention of polyp recurrence with curcumin followed by silibinin in a case
      of multiple colorectal adenomas.
AB  - Chemoprevention is a practical approach to reduce the risk of various cancers
      including colorectal cancer (CRC). The goal is to reduce the incidence of pre
      neoplastic adenomatous polyps and prevent its progression to CRC. Curcumin and
      silibinin prevent intestinal polyp formation in mice. Curcumin sensitizes
      silymarin to exert synergistic anticancer activity in colon cancer cells.
      Patients presenting with multiple colorectal adenomatous polyps (MCRA) have a
      high lifetime risk for CRC. We present a 57-year-old man with MCRA, without
      deleterious germline APC or MYH mutations. Our patient had 54 polyps in the first
      colonoscopy, most of 3 to 8 mm and one of 20 mm with high grade dysplasia /
      adenocarcinoma. Four subsequent colonoscopies showed continuous development of
      adenomatous polyps treated by polypectomy for the most part and some with heat.
      After the treatment with curcumin for 3 months and a half followed by silibinin
      for 9 months, we find many less polyps than in the previous colonoscopies, going
      from the finding of 40 adenomas of 3-6 mm in the pre-treatment colonoscopy to 3
      polyps after treatment.

PMID- 29072083
TI  - Recurrence of infection and diversity of Helicobacter pylori strains in an adult
      population in Mexico treated with empirical standard triple therapy.
AB  - BACKGROUND: After eradication treatment for Helicobacter pylori, infection could
      recur due to recrudescence or re-infection. The objective of this study was to
      determine the recurrence of Helicobacter pylori infection and identify virulent
      Helicobacter pylori strains one year after eradication with standard triple
      therapy. MATERIAL AND METHODS: A quasi-experimental study was performed that
      included a patient population with digestive diseases associated with
      Helicobacter pylori who had received standard triple therapy. Cultures and
      Polymerase Chain Reaction was performed on gastric biopsies for strain
      identification in all patients prior to eradication treatment and those with a
      positive carbon 14 breath test one year after eradication treatment. Statistical
      analysis was performed using the student T test and Fisher's exact test,
      statistical significance was set at 0.05. RESULTS: 128 patients were studied, 51
      (39.8%) were male and 77 (60.2%) were female with an average age of 54.8 years
      (DE 13.8). There was an annual recurrence of Helicobacter pylori infection in 12
      (9.3%) patients. An annual re-infection and recrudescence occurred in 9 (7 %) and
      3 (2.3%) patients respectively. The recrudescence rate for cagA was 1/30 (3.3%)
      patients and 2/112 (1.8%) patients for vacA. The re-infection rate for cagA was
      3/30 (10%) patients and 6/112 (5.3%) patients for vacA. CONCLUSIONS: The
      recurrence of infection in this study was higher than that recorded in developed
      countries with a low prevalence of H. pylori and lower than that recorded in
      developing countries with a higher prevalence of H. pylori. The cagA or vacA
      s2/m2 strains were isolated after re-infection and recrudescence.

PMID- 29072084
TI  - Hepatitis with a multiple etiology in HIV-positive men who have sexual relations
      with other men.
AB  - Acute hepatitis C virus (HCV) is now a major health problem, mainly in men who
      have sexual relations with other men (MSM). Hepatitis E virus (HEV) causes
      sporadic cases of acute hepatitis. In this article, we describe two cases of
      acute hepatitis due to HCV with an interesting clinical progress.

PMID- 29072085
TI  - BSRM Annual Meeting - Manchester 2016: Free Paper Abstracts.

PMID- 29072086
TI  - A pilot randomized controlled trial of on-line interventions to improve sleep
      quality in adults after mild or moderate traumatic brain injury.
AB  - OBJECTIVE: To explore feasibility and potential efficacy of on-line interventions
      for sleep quality following a traumatic brain injury (TBI). DESIGN: A two
      parallel-group, randomized controlled pilot study. SETTING: Community-based.
      SUBJECTS: In all, 24 participants (mean age: 35.9 +/- 11.8 years) who reported
      experiencing sleep difficulties between 3 and 36 months after a mild or moderate
      TBI. INTERVENTIONS: Participants were randomized to receive either a cognitive
      behaviour therapy or an education intervention on-line. Both interventions were
      self-completed for 20-30 minutes per week over a six-week period. MAIN MEASURES:
      The Pittsburgh Sleep Quality Index assessed self-reported sleep quality with
      actigraphy used as an objective measure of sleep quality. The CNS Vital Signs on
      line neuropsychological test assessed cognitive functioning and the Rivermead
      Post-concussion Symptoms and Quality of Life after Brain Injury questionnaires
      were completed pre and post intervention. RESULTS: Both programmes demonstrated
      feasibility for use post TBI, with 83.3% of participants completing the
      interventions. The cognitive behaviour therapy group experienced significant
      reductions ( F = 5.47, p = 0.04) in sleep disturbance (mean individual change = 
      4.00) in comparison to controls post intervention (mean individual change = 
      1.50) with a moderate effect size of 1.17. There were no significant group
      differences on objective sleep quality, cognitive functioning, post-concussion
      symptoms or quality of life. CONCLUSION: On-line programmes designed to improve
      sleep are feasible for use for adults following mild-to-moderate TBI. Based on
      the effect size identified in this pilot study, 128 people (64 per group) would
      be needed to determine clinical effectiveness.

PMID- 29072087
TI  - Respiratory muscle function and exercise limitation in patients with chronic
      obstructive pulmonary disease: a review.
AB  - INTRODUCTION: Respiratory muscle dysfunction is common and contributes to dyspnea
      and exercise limitation in patients with chronic obstructive pulmonary disease
      (COPD). Improving dynamic function of respiratory muscles during exercise might
      help to reduce symptoms and improve exercise capacity. Areas covered: The aims of
      this review are to 1) summarize physiological mechanisms linking respiratory
      muscle dysfunction to dyspnea and exercise limitation; 2) provide an overview of
      available therapeutic approaches to better maintain load-capacity balance of
      respiratory muscles during exercise; and 3) to summarize current knowledge on
      potential mechanisms explaining effects of interventions aimed at optimizing
      dynamic respiratory muscle function with a special focus on inspiratory muscle
      training. Expert commentary: Several mechanisms which are potentially linking
      improvements in dynamic respiratory muscle function to symptomatic and functional
      benefits have not been studied so far in COPD patients. Examples of underexplored
      areas include the study of neural processes related to the relief of acute
      dyspnea and the competition between respiratory and peripheral muscles for
      limited energy supplies during exercise. Novel methodologies are available to non
      invasively study these mechanisms. Better insights into the consequences of
      dynamic respiratory muscle dysfunction will hopefully contribute to further
      refine and individualize therapeutic approaches in patients with COPD.

PMID- 29072088
TI  - The association between cement type and the subsequent risk of revision surgery
      in primary total hip replacement.
AB  - Background and purpose - To further improve the success of joint replacement
      surgery, attention needs to be paid to variations associated with improved or
      worsened outcomes. We investigated the association between the type of bone
      cement used and the risk of revision surgery after primary total hip replacement.
      Methods - We conducted a prospective study of data from the National Joint
      Registry for England and Wales between April 1, 2003 and December 31, 2013.
      199,205 primary total hip replacements performed for osteoarthritis where bone
      cement was used were included. A multilevel over-dispersed piecewise Poisson
      model was used to estimate differences in the rate of revision by bone cement
      type adjusted for implant type, head size, age, sex, ASA grade, and surgical
      approach. Results - The rate of revision was higher in DePuy CMW3 medium
      viscosity with gentamicin (IRR 2.0, 95% CI 1.5-2.7) and DePuy SmartSet high
      viscosity plain (IRR 2.7, 95% CI 1.1-5.5), and lower in DePuy CMW1 high viscosity
      plain (IRR 0.44, 95% CI 0.19-0.89) bone cements compared with Heraeus Palacos
      high viscosity with gentamicin. Revision rates were similar between plain and
      antibiotic-loaded bone cement. Interpretation - The majority of bone cements
      performed similarly well, excluding DePuy SmartSet high viscosity and CMW3 high
      viscosity with gentamicin, which both had higher revision rates. We found no
      clear differences by viscosity or antibiotic content.

PMID- 29072089
TI  - Hyperimmune globulin in pregnancy for the prevention of congenital
      cytomegalovirus disease.
AB  - INTRODUCTION: Cytomegalovirus (CMV) is the most common and serious cause of
      congenital infections in developed countries since it is capable of infecting the
      fetus after both primary and recurrent maternal infection, and can be spread for
      years by infected children. Areas covered: Animal and human pregnancy studies
      about the prevention of congenital CMV infection and disease by CMV-specific
      hyperimmune globulin (HIG). Commercial HIG is manufactured from the plasma of
      selected donors with high anti-CMV antibody avidity and titers. Expert
      commentary: Currently available experimental and clinical studies and case
      reports support the possible effectiveness and safety of HIG infusions in
      pregnancy for the prevention of congenital CMV disease. The knowledge about the
      potential efficacy of preventive or therapeutic HIG administration should be
      enlarged by multi-center randomized studies, which may be favored by the
      implementation of CMV screening. Meanwhile, if ultrasound examinations show signs
      of fetal injury, or CMV is detected in the amniotic fluid, the patients should be
      advised about the possible option of HIG therapy.

PMID- 29072090
TI  - Hospital cost impact of orbital atherectomy with angioplasty for critical limb
      ischemia treatment: a modeling approach.
AB  - AIM: The incremental cost of peripheral orbital atherectomy system (OAS) plus
      balloon angioplasty (BA) versus BA-only for critical limb ischemia was estimated.
      MATERIALS & METHODS: A deterministic simulation model used clinical and
      healthcare utilization data from the CALCIUM 360 degrees  trial and current cost
      data. Incremental cost of OAS + BA versus BA-only included differential
      utilization during the procedure and adverse-event costs at 3, 6 and 12-months.
      RESULTS: For every 100 procedures, incremental annual costs to the hospital were
      US$350,930 lower with OAS + BA compared with BA-only. Despite higher upfront
      costs, savings were realized due to reduced need for revascularization,
      amputation and end-of-life care over 6-12-month postoperative period. CONCLUSION:
      Atherectomy with OAS prior to BA was associated with cost savings to the
      hospital.

PMID- 29072091
TI  - Factors Associated With Wandering Behaviors in Veterans With Mild Dementia: A
      Prospective Longitudinal Community-Based Study.
AB  - OBJECTIVE: To investigate baseline factors associated with caregiver-reported
      wandering among community-dwelling veterans with mild dementia. METHODS: Veterans
      with mild dementia (N = 143) and their caregivers participated in a 2-year
      prospective longitudinal study. Measures assessed wandering, daily function,
      behavior, cognition, and personality features. Wandering was dichotomized as
      present or absent across study periods, and associations with baseline
      characteristics were examined. RESULTS: One-quarter of participants demonstrated
      caregiver-reported wandering at 1 or more study visits, with 14% to 15% wandering
      at any 1 visit. Wandering was associated with significantly lower baseline scores
      in performance of daily function, behavioral response to stress, gait, and
      balance, and conscientiousness. CONCLUSIONS: This novel study evaluated wandering
      in a community-dwelling sample of veterans with mild dementia. Wandering was
      associated with a specific personality trait, poorer behavioral response to
      stress as well as greater functional and gait/balance impairment. These findings
      may assist in developing community-based interventions for caregivers.

PMID- 29072092
TI  - Can rehabilitation improve the health and well-being in Friedreich's ataxia: a
      randomized controlled trial?
AB  - OBJECTIVE: To determine the effectiveness of a six-week rehabilitation programme
      followed by a home exercise programme for Friedreich's ataxia. DESIGN:
      Randomized, delayed-start control single-blind trial. SETTING: Outpatient
      rehabilitation centre. SUBJECTS: Ambulant or non-ambulant individuals with
      Friedreich's ataxia. INTERVENTION: Participants were randomized to a six-week
      outpatient rehabilitation programme, immediately (intervention group) or after a
      six-week delayed-start (control group). The rehabilitation was followed by a six
      week home exercise programme. MAIN MEASURES: The primary outcome was the
      Functional Independence Measure. Other measures included the Friedreich Ataxia
      Impact Scale and the Friedreich Ataxia Rating Scale. Outcomes were administered
      at baseline, 6, 12 and 18 weeks. RESULTS: Of 159 individuals screened, 92 were
      excluded and 48 declined to participate. A total of 19 participants were enrolled
      in the study. There was no significant difference in Functional Independence
      Measure change from baseline to six weeks in the intervention group (mean +/-
      standard deviation, 2.00 +/- 3.16) as compared to the control group (0.56 +/-
      4.06). Change in the Friedreich Ataxia Impact Scale body movement subscale
      indicated a significant improvement in health and well-being in the intervention
      group compared to the control group ( P = 0.003). Significant within-group
      improvements in the Friedreich Ataxia Impact Scale and the motor domain of the
      Functional Independence Measure post-rehabilitation were not sustained post-home
      exercise programme. CONCLUSION: Our study indicates that rehabilitation can
      improve health and well-being in individuals with Friedreich's ataxia; however, a
      larger study is required to have sufficient power to detect a significant change
      in the most sensitive measure of function, the motor domain of the Functional
      Independence Measure.

PMID- 29072094
TI  - Chemical diversity and anti-acne inducing bacterial potentials of essential oils
      from selected Elsholtzia species.
AB  - Essential oils from the aerial parts of four Elsholtzia species; Elsholtzia
      stachyodes, Elsholtzia communis, Elsholtzia griffithii and Elsholtzia beddomei
      were obtained by steam distillation and their chemical components were analysed
      by gas chromatography-mass spectrometry (GC-MS). Principle Component Analysis was
      used to identify the chemical variations in the essential oils from these plants,
      which could be categorised into two groups according to their main chemical
      components which are acylfuran derivatives and oxygenated monoterpenes.
      Additionally, the anti-acne inducing bacterial activity against Staphylococcus
      aureus and Staphylococcus epidermidis were evaluated. The oil from E. stachyodes
      was the most efficacious against the growth of S. aureus and S. epidermidis
      having MIC values of 0.78 and 1.56 MUL/mL, respectively, and exhibited five times
      more effective than erythromycin (standard antibiotic).

PMID- 29072095
TI  - In vitro and in vivo antitumour effects of phenylboronic acid against mouse
      mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells.
AB  - The cytotoxic activity of phenylboroxine acid was evaluated in vitro on mouse
      mammary adenocarcinoma 4T1, mouse squamous cell carcinoma SCCVII, hamster lung
      fibroblast V79 and mouse dermal fibroblasts L929 cell lines. The cytotoxic
      effects were dose dependent for all tested tumour and non-tumour cell lines.
      Under in vivo conditions, three application routes of phenylboronic acid were
      studied: intra-peritoneal (i.p.), intra-tumour (i.t.) and per-oral. After tumour
      transplantation in syngeneic mice, phenylboronic acid was shown to slow the
      growth of both tumour cell lines (4T1 and SCCVII) compared with the control. The
      inhibitory effects were pronounced during the application of phenylboronic acid.
      For both tested tumour cell lines, the most prominent antitumour effect was
      obtained by intraperitoneal administration, followed significantly by oral
      administration.

PMID- 29072093
TI  - The utility of 68Ga-DOTATATE positron-emission tomography/computed tomography in
      the diagnosis, management, follow-up and prognosis of neuroendocrine tumors.
AB  - Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI
      tract, pancreas and respiratory tract. The incidence of NETs has increased more
      than sixfold in the last decades. NETs typically express somatostatin receptors
      on their cell surface, which can be targeted by 'cold' somatostatin analogs for
      therapy or by 'hot' radiolabeled somatostatin analogs for tumor localization and
      treatment. 68-Gallium-DOTA peptides (DOTATATE, DOTATOC, DOTANOC) positron
      emission tomography/computed tomography is a highly accurate imaging modality for
      NETs that has been found to be more sensitive for NET detection than other
      imaging modalities. In the current review, we will discuss the clinical utility
      of 68-Gallium-DOTATATE positron emission tomography/computed tomography for the
      diagnosis and management of patients with NETs.

PMID- 29072096
TI  - Salvia broussonetii Benth.: aroma profile and micromorphological analysis.
AB  - The volatile profiles (VOC) and the essential oil (EO) composition from the
      aerial parts of Salvia broussonetii were analysed. Sesquiterpene hydrocarbons
      dominate the VOCs from leaves (95.7%) and flowers (67.6%), followed by
      monoterpene hydrocarbons (2.6 and 29.7%, respectively). The main common compounds
      are germacrene D, beta-bourbonene, alpha-pinene, alpha-copaene and alpha
      gurjunene, even if with divergent relative abundances. In the leaf EOs the
      sesquiterpenes prevail, even if not overwhelmingly (about 50.0%), followed by
      monoterpenes (23.0-35.0%) and by minor fractions of diterpene hydrocarbons and
      non-terpene derivates. The most abundant common compounds across the two sampling
      periods are alpha-pinene, beta-pinene, isobornyl acetate, alpha-gurjenene,
      germacrene D and bifloratriene. A morphological characterisation of the trichomes
      responsible for the productivity in terpenes was also performed. Four different
      morphotypes were observed on the above ground organs of S. brussonetii: peltates
      and capitates of type II and III resulted the only producers of volatile
      substances.

PMID- 29072098
TI  - Cytotoxic indole alkaloids from Nauclea orientalis.
AB  - A new indole alkaloid, nauclorienine (1), along with seven known alkaloids (2-8),
      were isolated from the stems and leaves of Nauclea orientalis. Among them,
      nauclorienine (1) was a new indole alkaloid holding a rare corynanthe-type
      skeleton, and the known compounds (2-8) were isolated from N. orientalis for the
      first time. Their structures were elucidated on the basis of extensive
      spectroscopic data analyses. All isolated compounds were evaluated for their
      cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF
      7 and SW480 in vitro. Alkaloids 1-4 exhibited significant inhibitory effects
      against various human cancer cell lines with IC50 values comparable to those of
      cisplatin.

PMID- 29072097
TI  - Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4
      yl)-indolizine derivatives. Part VII8-12.
AB  - A series of 13 compounds having a monoindolizine mono-salt skeleton was designed
      and synthesised in order to evaluate their antimycobacterial activity. The
      synthesis is efficient, involving only three steps: two alkylations and one 3 + 2
      dipolar cycloaddition. The antimicrobial activity against Mycobacterium
      tuberculosis H37Rv grown under aerobic conditions was evaluated, eight compounds
      showing a very good antimycobacterial activity. SAR correlation reveals a certain
      influence of the R substituent from the para position of benzoyl moiety at
      position 3 of indolizine. The most active five compounds passed the second stage
      of anti-TB testing, the assay demonstrating that they are potent against both
      replicating and non-replicating Mtb, have a bactericidal mechanism of action, are
      active against drug-resistant Mtb strains, present a moderate to good activity
      against nontuberculous mycobacteria, a good intracellular activity, and a
      moderate to high cytotoxicity. For one compound showing a promising anti-TB
      profile, a complete ADMET study has been performed.

PMID- 29072099
TI  - Stevia rebaudiana targeting alpha-amylase: An in-vitro and in-silico mechanistic
      study.
AB  - Diabetes mellitus (DM) is the fastest growing metabolic disorder in the world.
      Recently, more attention is paid to the study of natural products due to side
      effects of synthetic drugs. Stevia rebaudiana (Bertoni) is considered an
      encouraging starting point for the antidiabetic lead development. In the present
      study, the in vitro alpha-amylase inhibitory activity of the extracts of S.
      rebaudiana is investigated. In order to understand the molecular mechanism and
      future pharmacophore development, in silico study of secondary metabolites
      isolated from S. rebaudiana was carried out. Results indicated that water extract
      shows highest alpha-amylase inhibitory activity as compared to other extracts.
      Moreover, compound 20 (rebaudioside A) which has been previously reported and
      isolated from water extract showed the impressive binding profile with alpha
      amylase. Therefore, our study suggests that S. rebaudiana could be used in the
      development of therapeutic drugs for the treatment of diabetes.

PMID- 29072100
TI  - Gonadal dysfunction in adult male patients with thalassemia major: an update for
      clinicians caring for thalassemia.
AB  - INTRODUCTION: Hypogonadism is the most frequently reported endocrine
      complication, affecting 40%-80% of thalassemia major (TM) patients. The
      prevalence and severity of hypogonadism in TM varies among studies, depending on
      patients' age, genotype, transfusion frequency and starting age and efficiency of
      iron chelation. Areas covered: The diagnosis requires careful clinical assessment
      and appropriate laboratory testing. Its management is more complex compared to
      other 'classical' causes of hypogonadism because of multiple associated disorders
      (cardiac, hepatic and endocrine) and other contributing factors basically iron
      overload and iron toxicity. Expert commentary: Early recognition and treatment of
      hypogonadism in TM patients is most important to prevent late complications and
      to enhance the chances of parenthood. The goal of management is to restore
      deficient glandular function. If fertility is the issue and the testis is under
      stimulated because of gonadotropin deficiency, it is possible to induce or
      restore spermatogenesis with exogenous gonadotropins in some patients. Assisted
      reproductive techniques may supplementary help to overcome previously untreatable
      causes of male infertility. These positive achievements should encourage health
      care providers to pay closer attention to the reproductive health of TM patients.
      This would involve the collaboration of clinicians caring for thalassemia with
      endocrinologists and specialists in assisted reproductive technologies.

PMID- 29072101
TI  - Understanding mitochondrial biogenesis through energy sensing pathways and its
      translation in cardio-metabolic health.
AB  - Mitochondria play a pivotal role in physiological energy governance.
      Mitochondrial biogenesis comprises growth and division of pre-existing
      mitochondria, triggered by environmental stressors such as endurance exercise,
      caloric restriction, cold exposure and oxidative stress. For normal physiology,
      balance between energy intake, storage and expenditure is of utmost important for
      the coordinated regulation of energy homeostasis. In contrast, abnormalities in
      these regulations render the individual susceptible to cardiometabolic disorders.
      This review provides a comprehensive coverage and understanding on mitochondrial
      biogenesis achieved through energy-sensing pathways. This includes the complex
      coordination of nuclear, cytosolic and mitochondrial events involving energy
      sensors, transcription factors, coactivators and regulators. It focuses on the
      importance of mitochondrial biogenesis in cardiometabolic health. Lastly,
      converging on the benefits of caloric restriction and endurance exercise in
      achieving cardiometabolic health.

PMID- 29072102
TI  - Zinc and selenium modulate barium-induced oxidative stress, cellular injury and
      membrane-bound ATPase in the cerebellum of adult rats and their offspring during
      late pregnancy and early postnatal periods.
AB  - CONTEXT: Barium (Ba) may induce oxidative stress leading to tissues injury.
      OBJECTIVE: Our study investigated the therapeutic efficiency of zinc (Zn) and
      selenium (Se) against neurotoxicity induced by Ba in adult rats and their
      progeny. MATERIAL AND METHODS: Pregnant rats are exposed either to Ba (67 ppm),
      Ba + Zn, Ba + S or to only Zn and Se. RESULTS: In Ba-treated rats, there was an
      increase of MDA, H2O2, AOPP levels and SOD activity in the cerebellum of dams and
      their pups, a decrease in GPx, CAT, AChE, Na+K+-ATPase and Mg2+-ATPase
      activities, GSH and NPSH levels. These changes were confirmed by histological
      damages. Co-administration of Zn or Se to Ba-treated rats ameliorated the
      biochemical and histological aspects. CONCLUSION: Our results revealed that Zn
      and Se have shown promising effects against Ba toxicity in the cerebellum of
      adult rats and their suckling pups.

PMID- 29072103
TI  - Posterior cortical atrophy of a suspected non-Alzheimer type: a case report.
AB  - OBJECTIVE: A case of Posterior Cortical Atrophy syndrome of a suspected non
      Alzheimer disease pathology type is presented to illustrate prospective diagnosis
      and course. METHOD: A 54-year-old woman with vague memory complaints underwent
      serial neuropsychological assessment, MRI, PET, and CSF screening; data are
      reviewed. RESULTS: While early diagnosis was confounded by multiple factors,
      classic visuospatial symptoms were later demonstrated using routine
      neuropsychological methods. Serial MRI, PET, and CSF screening argued strongly
      for an alternative underlying pathology to AD. At age 59, her condition had
      progressed to dementia. CONCLUSIONS: Findings underscore the need for further
      research on suspected non-amyloid-based pathologies.

PMID- 29072104
TI  - Two new phenylpropanoids from the Chinese mangrove Ceriops tagal.
AB  - Two new phenylpropanoids, tagalphenylpropanoidins A-B (1-2), together with a
      known analogue, 2,3,6-trimethoxy-5-(1-propenyl)phenol (3), were isolated from the
      ethanolic extract of the Chinese mangrove Ceriops tagal. The structures of these
      compounds were determined by extensive spectroscopic analysis, including 1D and
      2D NMR and HR-ESI-MS, as well as the comparison with data in the literature.
      Compound 3 was discovered from this plant for the first time. Cytotoxicities of
      the three compounds against MCF-7 and HL-60 cancer cell lines were also
      evaluated.

PMID- 29072106
TI  - Auditory attention in autism spectrum disorder: An exploration of volumetric
      magnetic resonance imaging findings.
AB  - Studies have shown that individuals with autism spectrum disorder (ASD) tend to
      perform significantly below typically developing individuals on standardized
      measures of attention, even when controlling for IQ. The current study sought to
      examine within ASD whether anatomical correlates of attention performance
      differed between those with average to above-average IQ (AIQ group) and those
      with low-average to borderline ability (LIQ group) as well as in comparison to
      typically developing controls (TDC). Using automated volumetric analyses, we
      examined regional volume of classic attention areas including the superior
      frontal gyrus, anterior cingulate cortex, and precuneus in ASD AIQ (n = 38) and
      LIQ (n = 18) individuals along with 30 TDC. Auditory attention performance was
      assessed using subtests of the Test of Memory and Learning (TOMAL) compared among
      the groups and then correlated with regional brain volumes. Analyses revealed
      group differences in attention. The three groups did not differ significantly on
      any auditory attention-related brain volumes; however, trends toward significant
      size-attention function interactions were observed. Negative correlations were
      found between the volume of the precuneus and auditory attention performance for
      the AIQ ASD group, indicating larger volume related to poorer performance.
      Implications for general attention functioning and dysfunctional neural
      connectivity in ASD are discussed.

PMID- 29072105
TI  - Synthesis and biological evaluation of histamine Schiff bases as carbonic
      anhydrase I, II, IV, VII, and IX activators.
AB  - A series of 20 histamine Schiff base was synthesised by reaction of histamine, a
      well known carbonic anhydrase (CA, E.C 4.2.2.1.) activator pharmacophore, with
      substituted aldehydes. The obtained histamine Schiff bases were assayed as
      activators of five selected human (h) CA isozymes, the cytosolic hCA I, hCA II,
      and hCA VII, the membrane-anchored hCA IV and transmembrane hCA IX. Some of these
      compounds showed efficient activity (in the nanomolar range) against the
      cytosolic isoform hCA VII, which is a key CA enzyme involved in brain metabolism.
      Moderate activity was observed against hCA I and hCA IV (in the nanomolar to low
      micromolar range). The structure-activity relationship for activation of these
      isoforms with the new histamine Schiff bases is discussed in detail based on the
      nature of the aliphatic, aromatic, or heterocyclic moiety present in the aldehyde
      fragment of the molecule, which may participate in diverse interactions with
      amino acid residues at the entrance of the active site, where activators bind,
      and which is the most variable part among the different CA isoforms.

PMID- 29072107
TI  - Conformational transitions of uracil transporter UraA from Escherichia coli: a
      molecular simulation study.
AB  - The Escherichia coli uracil/H + symporter UraA, known as the representative
      nucleobase/cation symporter 2(NCS2) protein, gets involved in several crucial
      physiological processes for most living organisms on Earth, such as the uptake of
      nucleobases and transport of vitamin C. Some experiments proposed a working model
      to explain proton-coupling and uracil transporting process of UraA on the basis
      of the crystal structure of NCS2 protein, but the details of conformational
      changes remained unknown. Thus, in order to make clear conformational changes
      caused by the protonation and deprotonation process of some conserved proton
      coupled residues, the molecular dynamics simulation was used to study the
      conformation of UraA complexes in different protonation states. The results
      demonstrated that the protonation of residue Glu241 and Glu290 resulted in the
      whole conformational transition from the inward-open to the outward-open state.
      It can be concluded that Glu290 was crucial in a network of hydrogen-bonds in the
      middle of the core domain involving another essential residue, mainly including
      tyr288 in TM8, Tyr342, Ser338 in TM12, and the network of hydrogen-bonds was the
      key to maintain the stability of conformation. Protonation of Glu290 affects the
      stability of network of H-bond and changed the domains TM3 TM10 TM12. Thus,
      Glu290 may play a vital role as a 'proton trigger' that affects spatial
      structural of amino and residues near substrate binding side leading to an
      outward-open conformation transition.

PMID- 29072108
TI  - Adjusting for selective non-participation with re-contact data in the FINRISK
      2012 survey.
AB  - AIMS: A common objective of epidemiological surveys is to provide population
      level estimates of health indicators. Survey results tend to be biased under
      selective non-participation. One approach to bias reduction is to collect
      information about non-participants by contacting them again and asking them to
      fill in a questionnaire. This information is called re-contact data, and it
      allows to adjust the estimates for non-participation. METHODS: We analyse data
      from the FINRISK 2012 survey, where re-contact data were collected. We assume
      that the respondents of the re-contact survey are similar to the remaining non
      participants with respect to the health given their available background
      information. Validity of this assumption is evaluated based on the
      hospitalisation data obtained through record linkage of survey data to the
      administrative registers. Using this assumption and multiple imputation, we
      estimate the prevalences of daily smoking and heavy alcohol consumption and
      compare them to estimates obtained with a commonly used assumption that the
      participants represent the entire target group. RESULTS: When adjusting for non
      participation using re-contact data, higher prevalence estimates were observed
      compared to prevalence estimates based on participants only. Among men, the
      smoking prevalence estimate was 28.5% (23.2% for participants) and heavy alcohol
      consumption prevalence was 9.4% (6.8% for participants). Among women, smoking
      prevalence was 19% (16.5% for participants) and heavy alcohol consumption was
      4.8% (3% for participants). CONCLUSIONS: The utilisation of re-contact data is a
      useful method to adjust for non-participation bias on population estimates in
      epidemiological surveys.

PMID- 29072109
TI  - Resveratrol-based cinnamic ester hybrids: synthesis, characterization, and anti
      inflammatory activity.
AB  - Twenty-three novel resveratrol-based cinnamic ester hybrids were designed and
      synthesized. All the compounds were evaluated for their anti-inflammatory
      activity using RAW264.7 cells. Among them, compound D15 was found to be the most
      potent one in inhibiting NO production in LPS-stimulated RAW264.7 cells. The
      further study indicated that compound D15 could suppress expression of proteins
      iNOS, COX-2, p-p65, and p-IkappaB LPS-induced. Immunofluorescence further
      revealed compound D15 could reduce activation p65 in nuclei. All the results
      indicated that the anti-inflammatory activity of title compound may partly due to
      its inhibitory effect on the NF-kappaB signaling pathway.

PMID- 29072111
TI  - Optimizing the selection of organic waste for biomethanization.
AB  - This study evaluates the feasibility of using simultaneous mass balances of
      different nutrients as a tool for optimizing feeding composition in anaerobic
      digestion. Different ratios, among them total chemical oxygen demand/total
      Kjeldahl nitrogen (TCOD/TKN) and soluble chemical oxygen demand/TCOD (SCOD/TCOD),
      were assessed. The TCOD/total volatile solids (TVS) ratio was 1.73 kg O2/kg TVS,
      while, with the exception of the sewage sludge, pig slurry and animal wastes, a
      linear relationship was established between phosphorus and nitrogen (0.06 kg P/kg
      TKN (R2 = 0.9045)). The study was applied to different mixtures of waste
      (cucumber, quince, tomato, strawberry waste, vinasse, glycerol, tomato plant, pig
      slurry, sewage sludge, fish waste, landfill leachate and viscera). The mass
      balance was performed for 50 mixtures chosen at random, containing three
      different wastes. After evaluating the theoretical optimal values determined by
      the mass balances, the most promising data were compared with the experimental
      results of the anaerobic co-digestion of one of the three waste mixtures. As
      predicted by the mass balances, the codigestion of glycerol, strawberry extrudate
      and fish waste (41:54:4 in VS) improved methane production to a maximum value of
      0.308 m3 CH4/kg TVSadded for an organic loading rate of 0.62-4.26 kg TVS/m3.d.

PMID- 29072110
TI  - Using pharmacists and drugstore workers as sexual healthcare givers: a
      qualitative study of men who have sex with men in Dar es Salaam, Tanzania.
AB  - BACKGROUND: Previous research has shown that men who have sex with men (MSM)
      avoid formal healthcare services because of the fear of discrimination as
      homosexuality is illegal and stigmatized in Tanzania. Instead, self-treatment by
      medications obtained directly from pharmacies or drugstores may be common when
      MSM experience symptoms of suspected sexually transmitted infections (STIs)
      related to sexual activity with men. OBJECTIVE: To explore MSM's perceptions and
      experiences of seeking treatment and advice from pharmacists and drugstore
      workers in Dar es Salaam, Tanzania, with regards to their sexual health and STI
      related problems. MATERIALS AND METHODS: 15 in-depth interviews were conducted
      with MSM with experience of seeking assistance relating to their sexual health at
      pharmacies and drugstores in Dar es Salaam in 2016. A qualitative manifest and
      latent content analysis was applied to the collected data. RESULTS: Four themes
      related to different aspects of MSM's perceptions and experiences of pharmacy
      care emerged from the analysis: (1) Balancing threats against need for treatment
      reflected informants' struggles concerning risks and benefits of seeking
      assistance at pharmacies and drugstores; (2) Identifying strategies to access
      required services described ways of approaching a pharmacist when experiencing a
      sexual health problem; (3) Seeing pharmacists as a first choice of care focused
      on informants' reasons for preferring contact with pharmacies/drugstores rather
      than formal healthcare services; and (4) Lacking reliable services at pharmacies
      indicated what challenges existed related to pharmacy care. CONCLUSIONS: MSM
      perceived the barriers for accessing assistance for STI and sexual health
      problems at pharmacies and drugstores as low, thereby facilitating their access
      to potential treatment. However, the results further revealed that MSM at times
      received inadequate drugs and consequently inadequate treatment. Multi-facetted
      approaches are needed, both among MSM and drugstore, pharmacy, and healthcare
      workers, to improve knowledge of MSM sexual health, STI treatment, and risks of
      antibiotic resistance.

PMID- 29072112
TI  - Hydroxyethylamine derivatives as HIV-1 protease inhibitors: a predictive QSAR
      modelling study based on Monte Carlo optimization.
AB  - Application of HIV-1 protease inhibitors (as an anti-HIV regimen) may serve as an
      attractive strategy for anti-HIV drug development. Several investigations suggest
      that there is a crucial need to develop a novel protease inhibitor with higher
      potency and reduced toxicity. Monte Carlo optimized QSAR study was performed on
      200 hydroxyethylamine derivatives with antiprotease activity. Twenty-one QSAR
      models with good statistical qualities were developed from three different splits
      with various combinations of SMILES and GRAPH based descriptors. The best models
      from different splits were selected on the basis of statistically validated
      characteristics of the test set and have the following statistical parameters: r2
      = 0.806, Q2 = 0.788 (split 1); r2 = 0.842, Q2 = 0.826 (split 2); r2 = 0.774, Q2 =
      0.755 (split 3). The structural attributes obtained from the best models were
      analysed to understand the structural requirements of the selected series for HIV
      1 protease inhibitory activity. On the basis of obtained structural attributes,
      11 new compounds were designed, out of which five compounds were found to have
      better activity than the best active compound in the series.

PMID- 29072113
TI  - Erratum.

PMID- 29072115
TI  - Fearful asymmetry: Bouillaud, Dax, Broca, and the localization of language,
      Paris, 1825-1879.

PMID- 29072114
TI  - A customised cold-water immersion protocol favours one-size-fits-all protocols in
      improving acute performance recovery.
AB  - The purpose of the present study was to investigate whether a customised cold
      water immersion (CWIc) protocol was more effective in enhancing acute performance
      recovery than a one-size-fits-all CWI (CWIs) or active recovery (AR) protocol. On
      three separate testing days, 10 healthy, physically active, non-smoking males
      completed the same fatiguing protocol (60 squat jumps and a 2'30" all-out cycling
      time-trial) followed by CWIc (12 degrees C, 10-17 min), CWIs (15 degrees C, 10
      min) or AR (60 W, 10 min). Outcome measures to assess acute recovery were heart
      rate variability (HRV) as HRVrecovery, muscle power (MP) as absolute and relative
      decline, and muscle soreness (MS) at 0 and 24 h. HRVrecovery for CWIc was
      significantly higher compared to CWIs (p = .026, r = 0.74) and AR (p = .000, r =
      0.95). The relative decline in MP after CWIc was significantly lower than after
      CWIs (p = .017, r = 0.73). MS 0 h and MS 24 h post-intervention were not
      different after CWIc compared to CWIs and AR (p > .05). The findings of the
      present study demonstrated that CWIc outperforms CWIs and AR in the acute
      recovery of cardiovascular (HRV) and CWIs in neuromuscular (MP) performance with
      no differences in MS. To optimise the effects of CWI, contributions of the
      protocol duration and water temperature should be considered to guarantee an
      optimal customised dose.

PMID- 29072116
TI  - Attachment of anaerobic ammonium-oxidizing bacteria to augmented carrier
      material.
AB  - The formation of stable and highly active anammox biofilm is a lengthy process
      leading to long start-up times of deammonifying reactors of several months or
      more. This study aims to provide a quick solution to the problem of long start-up
      periods by pretreating the surface of carrier material. Two different techniques
      were investigated. The first one focused on growing a layer of heterotrophic
      biofilm on the surface of the plastic carriers prior to inoculation with anammox
      biomass. Specific anammox activity increased by almost 400% as compared to seed
      values and was equal to 250 mg NH4-N/gVSS/L*d. In the second technique, the
      carrier material was coated with a layer of granular-activated carbon to provide
      a higher surface area. The anammox activity increased by approximately 50%. In
      comparison, the control reactor did not develop any biofilm and no anammox
      activity was detected. Rapid attachment of the anammox biomass was achieved in a
      reactor with media that had a predeveloped layer of a biofilm. In a way, this
      approach is analogous to a primer or an undercoat that is put on materials before
      painting to ensure better adhesion of paint to the surface, hence the suggested
      name - bioprimer.

PMID- 29072117
TI  - Investigation of phyco-remediation of road salt run-off with marine microalgae
      Nannochloropsis gaditana.
AB  - Phyco-remediation is an environmental-friendly method, which involves the
      application of beneficial microalgae to treat wastewater-containing pollutants
      for a diverse range of conditions. Several industrial processes generate hyper
      saline wastewater, which is a significant challenge for conventional wastewater
      treatment, and the disposal of saline waters also has a negative impact on the
      environment. Road salt run-off is one such saline wastewater stream not currently
      treated and one that contributes significantly to negatively impacting receiving
      bodies of water. In this study, Nannochloropsis microalgae were able to
      assimilate >95% of the nitrates within 8 days in road salt concentrations ranging
      from 2.6% to 4.4% under phototrophic cultivation mode. Biomass yields of 1-2 g/l
      of culture were obtained with the maximum lipid of 22% (g/g) biomass in the road
      salt media. The crude road salt media provided all the essential micronutrients
      needed for algal cultivation. The fatty acid composition analysis of the obtained
      lipid composed of C16 and C18 over 45% of FAME are suitable for biofuel. This
      study has established that the use of road salt containing nitrate and phosphate
      nutrients will support the growth of marine micro algae for remediation of a
      waste water system that are the concern at winter-prevalent regions.

PMID- 29072118
TI  - Multiple spectroscopic studies of the interaction between a quaternary ammonium
      based cationic Gemini surfactant (as a carrier) and human erythropoietin.
AB  - Erythropoietin (EPO) is a hematopoietic growth factor. This substance, as a
      strong cell protector, can increase cell maintenance during different damages of
      central nervous system. Since the brain-blood barrier prevents the entrance of
      large proteins similar to EPO into the brain, its systemic delivery gets limited.
      The aim of this study was to find an alternative approach for EPO delivery into
      the brain to skip the blood-brain barrier prevention. So, a new quaternary
      ammonium-based cationic Gemini surfactant has been used to study the interaction
      of the cationic Gemini surfactant (as a carrier) with EPO using various
      spectroscopic techniques of (fluorescence and circular dichroism (CD)) and
      thermal denaturation. Fluorescence spectroscopy studies show the formation of
      Gemini-EPO complex and also static quenching of protein upon this interaction.
      The binding parameters of number of binding sites, binding affinity, Gibbs free
      energy, enthalpy, and entropy were calculated according to fluorescence quenching
      studies. Also, CD results have further represented that the content of regular
      secondary structure of EPO did not show any significant alterations by increasing
      the Gemini concentration. Finally, thermal denaturation behavior of EPO results
      indicates decreasing the thermal stability of protein in the presence of Gemini.
      In conclusion, the obtained results proposed that Gemini as a cationic surfactant
      can bind to EPO without any significant diverse effects on the structure of this
      drug (EPO) which can be considered as a candidate for EPO delivery in future.

PMID- 29072119
TI  - Prevalence, perceptions, and consequences of substance use in medical students.
AB  - BACKGROUND: Research regarding the health and wellness of medical students has
      led to ongoing concerns regarding patterns of alcohol and drug use that take
      place during medical education. Such research, however, is typically limited to
      single-institution studies or has been conducted over 25 years ago. OBJECTIVE:
      The objective of the investigation was to assess the prevalence and consequences
      of medical student alcohol and drug use and students' perceptions of their
      medical school's substance-use policies. DESIGN: A total of 855 medical students
      representing 49 medical colleges throughout the United States participated in an
      online survey between December 2015 and March 2016. RESULTS: Data showed that
      91.3% and 26.2% of medical students consumed alcohol and used marijuana
      respectively in the past year, and 33.8% of medical students consumed five or
      more drinks in one sitting in the past two weeks. Differences in use emerged
      regarding demographic characteristics of students. Consequences of alcohol and
      drug use in this sample of medical students included but were not limited to
      interpersonal altercations, serious suicidal ideation, cognitive deficits,
      compromised academic performance, and driving under the influence of substances.
      Forty percent of medical students reported being unaware of their medical
      institution's substance-use policies. CONCLUSIONS: Findings suggest that
      substance use among medical students in the US is ongoing and associated with
      consequences in various domains. There is a lack of familiarity regarding school
      substance-use policies. Although there has been some progress in characterizing
      medical student alcohol use, less is known about the factors surrounding medical
      students' use of other substances. Updated, comprehensive studies on the patterns
      of medical student substance use are needed if we are to make the necessary
      changes needed to effectively prevent substance-use disorders among medical
      students and support those who are in need of help.

PMID- 29072120
TI  - LCA of an ice cream cup of polyethylene coated paper: how does the choice of the
      end-of-life affect the results?
AB  - This study presents an evaluation of the environmental performance of an ice
      cream cup made of polyethylene (PE)/paper laminate using a life cycle assessment
      approach 'from cradle to grave'. Two opposite alternative disposal scenarios, as
      well as their intermediate combinations, were considered: 100% incineration and
      100% landfilling. The environmental impacts were calculated using the EPD 2013
      evaluation method since the study was developed in an Environmental Product
      Declaration perspective as well as the method ReCiPe 2008 H at the endpoint
      level. PE/paper laminate production was the most impactful process since it
      provided the highest contribution to total impacts in four of six impact
      categories considered. Ice cream cup production was the second impactful process.
      The 100% incineration scenario provided negligible contribution to life cycle
      total impact for all impact categories; while considering the landfilling
      scenario, the percentage contributions to the total impact provided by the end-of
      life phase increased considerably, until to be comparable to the contributions
      provided by the production processes of the PE/paper laminate and the ice cream
      cup. The obtained results highlighted that different disposal scenarios can
      affect significantly the conclusions of a study. At the endpoint level,
      incineration was more environmentally sound than landfilling for all the ReCiPe
      damage categories.

PMID- 29072121
TI  - Colonic stasis and chronic constipation: Demystifying proposed risk factors for
      colon polyp formation in a spinal cord injury veteran population.
AB  - BACKGROUND AND AIMS: Patients with spinal cord injury (SCI) suffer significant
      morbidity from neurogenic bowel. Chronic constipation has long-been a proposed
      risk factor for polyp development. We performed a retrospective cohort study in
      veterans with SCI to assess polyp presence in the setting of colonic stasis.
      METHODS: All consecutive patients at the James A. Haley Veterans Affairs Hospital
      with SCI and neurogenic bowel who completed screening colonoscopy between January
      1, 2004 to June 30, 2013 were included. Colonoscopies were excluded if they were
      aborted, not completed to the cecum, of less than adequate preparation, or if
      polypectomy was precluded. Patient data included level, duration, and
      completeness of SCI. Polyp data included number, location, and histology.
      RESULTS: 325 patients ultimately met inclusion criteria. Most were male (96%).
      The average age at screening colonoscopy was 62.8 years. The majority of patients
      had injury to the cervical spine (41.5%). Colon polyps were detected in 130
      patients (40%). Adenomatous change was seen in 95 (73%) of these patients. The
      adenoma detection rate (ADR) across all patients was 29.2%. Polyp presence and
      ADR demonstrated no statistically significant correlation with level, degree, or
      duration of SCI. Only patient age at time of screening colonoscopy had a
      significant correlation with polyp and adenoma presence (P<0.05). CONCLUSIONS:
      SCI had no statistically significant correlation with polyp or adenoma presence.
      The ADR in our veteran SCI population with chronic constipation is comparable
      with that reported in the general population.

PMID- 29072122
TI  - Use of rice husk in waste cooking oil pretreatment.
AB  - Since industrial wastes are increasing, the development of studies to find ways
      for their use is urgent. Waste cooking oil is an important source for the
      production of biodiesel, one of the main biofuels in Brazil. However, during
      cooking, the oil undergoes conditions that change its properties and decrease its
      quality, such as its acidity value. Current research treats waste cooking oil by
      the adsorption process using rice husk, an agro-industrial waste, and activated
      carbon to compare results. The potential of the adsorbents to remove free fatty
      acids in waste cooking oil has been investigated by the batch technique,
      evaluating different operating conditions of temperature, adsorbent mass and
      agitation. Adsorbents were characterized by nitrogen physisorption, scanning
      electron microscope, energy-dispersive spectroscopy and X-ray diffraction. The
      maximum result obtained for activated carbon at acidity reduction was 63%, using
      22.4 degrees C, 169.64 rpm and 3.39 g of adsorbent mass. Already, using the rice
      husk the percentage of removal was the same, 63% using 22.4 degrees C, 80.36 rpm
      and 1.61 g of adsorbent, however in shorter times. The results prove that the
      application of the rice husk for this purpose is advantageous, for being a low
      cost material, available on a large scale and that provide results similar to
      activated carbon.

PMID- 29072123
TI  - Opinions and Perceptions Regarding Traditional Male Circumcision With Related
      Deaths and Complications.
AB  - The notion of manhood values is highly treasured and respected by various
      cultural groups practicing traditional male circumcision (TMC) in South Africa.
      This study was conducted at Libode, Eastern Cape, South Africa. The goals of this
      study were to (a) explore opinions and perceptions related to TMC among boys from
      12 to 18 years of age, and (b) determine the actions to be taken to prevent high
      mortality and morbidity rates related to TMC. A simple random sampling was used
      to select three focus group discussions with 36 circumcised boys, and purposive
      sampling was used to select 10 key informants. The overarching themes collated
      included the following: (a) accepted age for circumcision, (b) causes attributed
      to deaths and complications, (c) TMC is preferred to medical male circumcision,
      and (d) acceptable community actions to prevent the problem. The study concludes
      with discussion and recommendation of a comprehensive health promotion program
      that is considerate of community opinions and perceptions in the prevention of
      deaths and complications affecting the circumcision initiates and at the same
      time respecting the culture.

PMID- 29072124
TI  - Efficacy of Low-Intensity Extracorporeal Shock Wave Therapy on Men With Chronic
      Pelvic Pain Syndrome Refractory to 3-As Therapy.
AB  - Managing patients with chronic pelvic pain syndrome (CPPS) refractory to the
      traditional 3-As therapy (antibiotics, alpha-blockers, and anti-inflammatories)
      is a challenging task. Low-intensity extracorporeal shock wave therapy (LI-ESWT)
      was recently reported to be able to improve pain, urinary symptoms, and even
      sexual function by inducing neovascularization and anti-inflammation, reducing
      muscle tone, and influencing nerve impulses. This study evaluates whether
      combined treatment with LI-ESWT can restore clinical ability and quality of life
      (QoL) in patients refractory to 3-As therapy. This was an open-label, single-arm
      prospective study. Patients with CPPS without more than a 6-point decrease in the
      National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total
      score under the maximal dosage of 3-As therapy were enrolled. LI-ESWT treatment
      consisted of 3,000 shock waves administered once weekly for 4 weeks. The NIH
      CPSI, visual analog scale (VAS) score, International Prostate Symptom Score
      (IPSS), and the five-item version of the International Index of Erectile Function
      (IIEF-5) were used to evaluate efficacy at 1, 4, and 12 weeks after LI-ESWT.
      Thirty-three patients were enrolled in this study. After LI-ESWT treatment, 27 of
      the 33 patients (81.82%) had a successful response to LI-ESWT, with a decrease of
      3.29 and 5.97 in the VAS score and total IPSS at the 3-month follow-up. Waist
      circumference was the only significant predictor of a successful response to LI
      ESWT. LI-ESWT can serve as a salvage therapy for patients with CPPS refractory to
      traditional 3-As therapy. Further studies are needed to determine an adequate
      therapeutic protocol and important predictors in patients with different CPPS
      etiologies.

PMID- 29072126
TI  - Extracting surface diffusion coefficients from batch adsorption measurement data:
      application of the classic Langmuir kinetics model.
AB  - Surface diffusion coefficients may be estimated by fitting solutions of a
      diffusion model to batch kinetic data. For non-linear systems, a numerical
      solution of the diffusion model's governing equations is generally required. We
      report here the application of the classic Langmuir kinetics model to extract
      surface diffusion coefficients from batch kinetic data. The use of the Langmuir
      kinetics model in lieu of the conventional surface diffusion model allows
      derivation of an analytical expression. The parameter estimation procedure
      requires determining the Langmuir rate coefficient from which the pertinent
      surface diffusion coefficient is calculated. Surface diffusion coefficients
      within the 10-9 to 10-6 cm2/s range obtained by fitting the Langmuir kinetics
      model to experimental kinetic data taken from the literature are found to be
      consistent with the corresponding values obtained from the traditional surface
      diffusion model. The virtue of this simplified parameter estimation method is
      that it reduces the computational complexity as the analytical expression
      involves only an algebraic equation in closed form which is easily evaluated by
      spreadsheet computation.

PMID- 29072125
TI  - The Effects of Ramadan Intermittent Fasting (RIF) on Spirometric Data of Stable
      COPD Patients: A Pilot Study.
AB  - No previous study has raised the effects of RIF on lung function data of chronic
      obstructive pulmonary disease (COPD) patients. The objective of the present study
      was to assess the effects of RIF on spirometric data measured in male patients
      with a stable COPD. Sixteen patients with stable COPD (mean +/- SD of age: 64 +/-
      7 years) who fasted during Ramadan volunteered to the study. Three sessions
      (Before-R, End-R, and After-R) were selected for spirometry tests that were
      consistently performed 2.5-4.5 hr before fasting break. Assessment sessions
      comprised: forced vital capacity (FVC), 1st s forced expiratory volume (FEV1),
      FEV1/FVC, peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), and
      forced expiratory flow rate at the x% of FVC to be exhaled (FEFx%). A
      reversibility test was performed only during the Before-Ramadan session.
      Spirometric data were expressed in percentages of local reference values.
      Findings were analyzed by applying repeated measures analysis of variance. The
      mean +/- SD of the postbronchodilator FEV1/FVC ratio and the FEV1 were,
      respectively, 0.52 +/- 0.14 and 48 +/- 19%. The mean +/- SD of FEV1 (Before-R: 47
      +/- 19, End-R: 45 +/- 18, After-R: 44 +/- 19%), FVC (Before-R: 73 +/- 18, End-R:
      71 +/- 16, After-R: 69 +/- 17%), FEV1/FVC (Before-R: 67 +/- 16, End-R: 66 +/- 16,
      After-R: 65 +/- 16%), PEF (Before-R: 46 +/- 19, End-R: 47 +/- 22, After-R: 45 +/-
      21%), MMEF (Before-R: 19 +/- 10, End-R: 18 +/- 8, After-R: 18 +/- 9%), FEF25%
      (Before-R: 16 +/- 6, End-R: 16 +/- 5, After-R: 15 +/- 5%), FEF50% (Before-R: 21
      +/- 14, End-R: 20 +/- 12, After-R: 20 +/- 12%) and FEF75% (Before-R: 27 +/- 19,
      End-R: 27 +/- 19, After-R: 27 +/- 19%) were not significantly influenced by RIF.
      RIF did not bring about any significant changes in the spirometric data of stable
      COPD male patients fasting the 2016 holy month of Ramadan.

PMID- 29072128
TI  - FBXW7 expression affects the response to chemoradiotherapy and overall survival
      among patients with oral squamous cell carcinoma: A single-center retrospective
      study.
AB  - FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein
      that regulates the degradation of various oncoproteins in several malignancies.
      However, limited information is available regarding FBXW7 expression in oral
      squamous cell carcinoma. Therefore, this study aimed to determine the clinical
      significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7
      expression patterns in oral squamous cell carcinoma and adjacent normal tissues
      from 15 patients who underwent radical resection were evaluated using
      quantitative real-time polymerase chain reaction and immunohistochemical
      staining. In addition, immunohistochemistry was performed using paraffin-embedded
      sections from biopsy specimens obtained from 110 patients with oral squamous cell
      carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The
      associations of FBXW7 expression with various clinicopathological features and
      prognosis were evaluated in these patients. As a results, in the 15 matched
      samples, the FBXW7 expression was significantly decreased in the oral squamous
      cell carcinoma tissues compared to that in the adjacent normal tissues. In the
      clinicopathological analysis, compared to high protein expression, low FBXW7
      expression was found to significantly associate with a poor histological response
      to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low
      FBXW7 expression was significantly associated with a poor prognosis, and FBXW7
      expression was found to be an independent predictor of overall survival in the
      multivariate analysis. Our results suggest that FBXW7 may function as a tumor
      suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a
      potential biomarker for predicting not only the clinical response to
      chemoradiotherapy but also overall survival in patients with oral squamous cell
      carcinoma.

PMID- 29072129
TI  - Cell-free mitochondrial DNA copy number variation in head and neck squamous cell
      carcinoma: A study of non-invasive biomarker from Northeast India.
AB  - Head and neck squamous cell carcinoma is the most commonly diagnosed cancer
      worldwide. The lifestyle, food habits, and customary practices manifest the
      Northeast Indian population toward higher susceptibility to develop head and neck
      squamous cell carcinoma. Here, we have investigated the association of smoke and
      smokeless tobacco, and alcohol with copy number variation of cell-free
      mitochondrial DNA and cell-free nuclear DNA in cases and controls. Cell-free DNA
      from plasma was isolated from 50 head and neck squamous cell carcinoma cases and
      50 controls with informed written consent using QIAamp Circulating Nucleic Acid
      Kit. Real-time polymerase chain reaction was done for copy number variation in
      cell-free mitochondrial DNA and cell-free nuclear DNA. Receiver operating
      characteristic curve analysis was performed to evaluate the diagnostic
      application between the two study groups using clinicopathological parameters.
      The levels of cell-free nuclear DNA and cell-free mitochondrial DNA of cases in
      association with smoke and smokeless tobacco, alcohol with smoking (p < 0.05)
      were significantly higher (p < 0.01 and p < 0.001, respectively) than controls.
      Using receiver operating characteristic curve analysis between head and neck
      squamous cell carcinoma cases and controls, we distinguished cell-free
      mitochondrial DNA (cutoff: 19.84 raw Ct; sensitivity: 84%; specificity: 100%; p <
      0.001) and cell-free nuclear DNA (cutoff: 463,282 genomic equivalent/mL;
      sensitivity: 53%; specificity: 87%; p < 0.001). The copy number variation in
      cases (cell-free nuclear DNA: 5451.66 genomic equivalent/mL and cell-free
      mitochondrial DNA: 29,103,476.15 genomic equivalent/mL) and controls (cell-free
      nuclear DNA: 1650.9 genomic equivalent/mL and cell-free mitochondrial DNA:
      9,189,312.54 genomic equivalent/mL), respectively. Our result indicates that the
      cell-free mitochondrial DNA content is highly associated with smoke and smokeless
      tobacco, betel quid chewing, and alcohol which shows greater promises, holding
      the key characteristics of diagnostic biomarkers, that is, minimal invasiveness,
      high specificity, and sensitivity.

PMID- 29072130
TI  - Glycoprotein CA19.9-specific monoclonal antibodies recognize sialic acid
      independent glycotope.
AB  - A repertoire of monoclonal antibodies was generated by immunization of mice with
      cancer-associated glycoprotein CA19.9, and two of them were selected as optimal
      capture and detecting counterparts for sandwich test system for detection of
      CA19.9. Fine epitope specificity of the antibodies was determined using printed
      glycan array, enzyme-linked immunosorbent assay, and inhibitory enzyme-linked
      immunosorbent assay. Unexpectedly, both immunoglobulins did not bind key epitope
      of CA19.9 glycoprotein, tetrasaccharide SiaLeA, as well as its defucosylated form
      sialyl LeC (known as CA-50 epitope). The antibodies were found to have different
      glycan-binding profiles; however, they recognized similar glycotopes with common
      motif Galbeta1-3GlcNAcbeta (LeC), thus resembling specificity of human natural
      cancer-associated anti-LeC antibodies. We propose that cancer-specific
      glycopeptide epitope includes Galbeta1-3GlcNAcbeta fragment of a glycoprotein O
      chain in combination with proximal hydrophobic amino acid(s) of the polypeptide
      chain.

PMID- 29072131
TI  - Cancer stem cells and differentiation therapy.
AB  - Cancer stem cells can generate tumors from only a small number of cells, whereas
      differentiated cancer cells cannot. The prominent feature of cancer stem cells is
      its ability to self-renew and differentiate into multiple types of cancer cells.
      Cancer stem cells have several distinct tumorigenic abilities, including stem
      cell signal transduction, tumorigenicity, metastasis, and resistance to
      anticancer drugs, which are regulated by genetic or epigenetic changes. Like
      normal adult stem cells involved in various developmental processes and tissue
      homeostasis, cancer stem cells maintain their self-renewal capacity by activating
      multiple stem cell signaling pathways and inhibiting differentiation signaling
      pathways during cancer initiation and progression. Recently, many studies have
      focused on targeting cancer stem cells to eradicate malignancies by regulating
      stem cell signaling pathways, and products of some of these strategies are in
      preclinical and clinical trials. In this review, we describe the crucial features
      of cancer stem cells related to tumor relapse and drug resistance, as well as the
      new therapeutic strategy to target cancer stem cells named "differentiation
      therapy."

PMID- 29072132
TI  - Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced
      hepatocellular carcinoma in mice.
AB  - Previous in vitro studies have demonstrated that miR-144 inhibits hepatocellular
      carcinoma cell proliferation, invasion, and migration. We have shown that miR
      144, injected intravenously, is taken up by the liver and induces endogenous
      hepatic synthesis of miR-144. We hypothesized that administered miR-144 has tumor
      suppressive effects on liver tumor development in vivo. The effects of miR-144 on
      tumorigenesis and tumor growth were tested in a diethylnitrosamine-induced
      hepatocellular carcinoma mouse model. MiR-144 injection had no effect on body
      weight but significantly reduced diethylnitrosamine-induced liver enlargement
      compared with scrambled microRNA. MiR-144 had no effect on diethylnitrosamine
      induced liver tumor number but reduced the tumor size above 50%, as evaluated by
      magnetic resonance imaging (scrambled microRNA 23.07 +/- 5.67 vs miR-144 10.38 +/
      2.62, p < 0.05) and histological analysis (scrambled microRNA 30.75 +/- 5.41 vs
      miR-144 15.20 +/- 3.41, p < 0.05). The levels of miR-144 was suppressed in tumor
      tissue compared with non-tumor tissue in all treatment groups (diethylnitrosamine
      phosphate-buffered saline non-tumor 1.05 +/- 0.09 vs tumor 0.54 +/- 0.08, p <
      0.01; diethylnitrosamine-scrambled microRNA non-tumor 1.23 +/- 0.33 vs tumor 0.44
      +/- 0.10, p < 0.05; diethylnitrosamine-miR-144 non-tumor 54.72 +/- 11.80 vs tumor
      11.66 +/- 2.75, p < 0.01), but injection of miR-144 greatly increased miR-144
      levels both in tumor and non-tumor tissues. Mechanistic studies showed that miR
      144 targets epidermal growth factor receptor and inhibits the downstream Src/AKT
      signaling pathway which has previously been implicated in hepatocellular
      carcinoma tumorigenesis. Exogenously delivered miR-144 may be a therapeutic
      strategy to suppress tumor growth in hepatocellular carcinoma.

PMID- 29072133
TI  - Association between Vitamin D receptor (Cdx2, Fok1, Bsm1, Apa1, Bgl1, Taq1, and
      Poly (A)) gene polymorphism and breast cancer: A systematic review and meta
      analysis.
AB  - The purpose of this systemic review and meta-analysis was to examine the
      relationship between VDR gene polymorphisms and breast cancer. Literature was
      searched through PubMed database, Google scholar, and the web of knowledge from
      December 2015 to January 2017 and consists of 34 studies (26,372 cases and 32,883
      controls). All statistical measures were done using STATA version 11.2. The
      heterogeneity among studies was tested using I2 statistics. Mantel-Haenszel
      method and DerSimonian-Laird method were used to combine data from studies using
      both random-effect model and fixed-effect model, respectively. Potential
      publication bias was evaluated by Egger's test. Sensitivity analysis was also
      performed to evaluate the quality and consistency in results. The results of this
      meta-analysis revealed that VDR gene polymorphisms (Bsm1 bb vs BB; SOR = 1.18,
      95% CI = 1.054-1.322, Apa1 aa vs AA; SOR = 1.18, 95% CI = 0.87-1.59, Poly (A) LL
      vs SS; SOR = 1.41, 95% CI = 1.06-1.88, Fok1 ff + Ff vs FF; SOR = 1.25, 95% CI =
      0.896-1.759, Apa1 aa+Aa vs AA; SOR = 1.13, 95% CI = 0.95-1.35, Poly (A) LL + LS
      vs SS; SOR = 1.19, 95% CI = 1.00-1.43, Poly (A) L vs S; SOR = 1.18, 95% CI = 1.03
      1.35) are associated with the breast cancer. Cdx2, Bgl1, and Taq1 do not show
      association with breast cancer. Thus, the finding of this meta-analysis concluded
      that VDR Bsm1, Apa1, Fok1, and Poly (A) gene polymorphisms may be susceptible for
      breast cancer development.

PMID- 29072134
TI  - Editorial:Brain Hemorrhages and Future Management.

PMID- 29072135
TI  - Detection and quantification of mitochondrial DNA deletions from next-generation
      sequence data.
AB  - BACKGROUND: Chromosomal deletions represent an important class of human genetic
      variation. Various methods have been developed to mine "next-generation"
      sequencing (NGS) data to detect deletions and quantify their clonal abundances.
      These methods have focused almost exclusively on the nuclear genome, ignoring the
      mitochondrial chromosome (mtDNA). Detecting mtDNA deletions requires special
      care. First, the chromosome's relatively small size (16,569 bp) necessitates the
      ability to detect extremely focal events. Second, the chromosome can be present
      at thousands of copies in a single cell (in contrast to two copies of nuclear
      chromosomes), and mtDNA deletions may be present on only a very small percentage
      of chromosomes. Here we present a method, termed MitoDel, to detect mtDNA
      deletions from NGS data. RESULTS: We validate the method on simulated and real
      data, and show that MitoDel can detect novel and previously-reported mtDNA
      deletions. We establish that MitoDel can find deletions such as the "common
      deletion" at heteroplasmy levels well below 1%. CONCLUSIONS: MitoDel is a tool
      for detecting large mitochondrial deletions at low heteroplasmy levels. The tool
      can be downloaded at http://mendel.gene.cwru.edu/laframboiselab/ .

PMID- 29072136
TI  - An effective approach to detecting both small and large complexes from protein
      protein interaction networks.
AB  - BACKGROUND: Predicting protein complexes from protein-protein interaction (PPI)
      networks has been studied for decade. Various methods have been proposed to
      address some challenging issues of this problem, including overlapping clusters,
      high false positive/negative rates of PPI data and diverse complex structures. It
      is well known that most current methods can detect effectively only complexes of
      size >=3, which account for only about half of the total existing complexes.
      Recently, a method was proposed specifically for finding small complexes (size =
      2 and 3) from PPI networks. However, up to now there is no effective approach
      that can predict both small (size <= 3) and large (size >3) complexes from PPI
      networks. RESULTS: In this paper, we propose a novel method, called
      CPredictor2.0, that can detect both small and large complexes under a unified
      framework. Concretely, we first group proteins of similar functions. Then, the
      Markov clustering algorithm is employed to discover clusters in each group.
      Finally, we merge all discovered clusters that overlap with each other to a
      certain degree, and the merged clusters as well as the remaining clusters
      constitute the set of detected complexes. Extensive experiments have shown that
      the new method can more effectively predict both small and large complexes, in
      comparison with the state-of-the-art methods. CONCLUSIONS: The proposed method,
      CPredictor2.0, can be applied to accurately predict both small and large protein
      complexes.

PMID- 29072137
TI  - Predicting combinative drug pairs towards realistic screening via integrating
      heterogeneous features.
AB  - BACKGROUND: Drug Combination is one of the effective approaches for treating
      complex diseases. However, determining combinative drug pairs in clinical trials
      is still costly. Thus, computational approaches are used to identify potential
      drug pairs in advance. Existing computational approaches have the following
      shortcomings: (i) the lack of an effective integration of heterogeneous features
      leads to a time-consuming training and even results in an over-fitted classifier;
      and (ii) the narrow consideration of predicting potential drug combinations only
      among known drugs having known combinations cannot meet the demand of realistic
      screenings, which pay more attention to potential combinative pairs among newly
      coming drugs that have no approved combination with other drugs at all. RESULTS:
      In this paper, to tackle the above two problems, we propose a novel drug-driven
      approach for predicting potential combinative pairs on a large scale. We define
      four new features based on heterogeneous data and design an efficient fusion
      scheme to integrate these feature. Moreover importantly, we elaborate appropriate
      cross-validations towards realistic screening scenarios of drug combinations
      involving both known drugs and new drugs. In addition, we perform an extra
      investigation to show how each kind of heterogeneous features is related to
      combinative drug pairs. The investigation inspires the design of our approach.
      Experiments on real data demonstrate the effectiveness of our fusion scheme for
      integrating heterogeneous features and its predicting power in three scenarios of
      realistic screening. In terms of both AUC and AUPR, the prediction among known
      drugs achieves 0.954 and 0.821, that between known drugs and new drugs achieves
      0.909 and 0.635, and that among new drugs achieves 0.809 and 0.592 respectively.
      CONCLUSIONS: Our approach provides not only an effective tool to integrate
      heterogeneous features but also the first tool to predict potential combinative
      pairs among new drugs.

PMID- 29072138
TI  - Fusing multiple protein-protein similarity networks to effectively predict lncRNA
      protein interactions.
AB  - BACKGROUND: Long non-coding RNA (lncRNA) plays important roles in many biological
      and pathological processes, including transcriptional regulation and gene
      regulation. As lncRNA interacts with multiple proteins, predicting lncRNA-protein
      interactions (lncRPIs) is an important way to study the functions of lncRNA. Up
      to now, there have been a few works that exploit protein-protein interactions
      (PPIs) to help the prediction of new lncRPIs. RESULTS: In this paper, we propose
      to boost the prediction of lncRPIs by fusing multiple protein-protein similarity
      networks (PPSNs). Concretely, we first construct four PPSNs based on protein
      sequences, protein domains, protein GO terms and the STRING database
      respectively, then build a more informative PPSN by fusing these four constructed
      PPSNs. Finally, we predict new lncRPIs by a random walk method with the fused
      PPSN and known lncRPIs. Our experimental results show that the new approach
      outperforms the existing methods. CONCLUSION: Fusing multiple protein-protein
      similarity networks can effectively boost the performance of predicting lncRPIs.

PMID- 29072139
TI  - NemoProfile as an efficient approach to network motif analysis with instance
      collection.
AB  - BACKGROUND: A network motif is defined as a statistically significant and
      recurring subgraph pattern within a network. Most existing instance collection
      methods are not feasible due to high memory usage issues and provision of limited
      network motif information. They require a two-step process that requires network
      motif identification prior to instance collection. Due to the impracticality in
      obtaining motif instances, the significance of their contribution to problem
      solving is debated within the field of biology. RESULTS: This paper presents
      NemoProfile, an efficient new network motif data model. NemoProfile simplifies
      instance collection by resolving memory overhead issues and is seamlessly
      generated, thus eliminating the need for costly two-step processing.
      Additionally, a case study was conducted to demonstrate the application of
      network motifs to existing problems in the field of biology. CONCLUSION:
      NemoProfile comprises network motifs and their instances, thereby facilitating
      network motifs usage in real biological problems.

PMID- 29072140
TI  - A sensitive short read homology search tool for paired-end read sequencing data.
AB  - BACKGROUND: Homology search is still a significant step in functional analysis
      for genomic data. Profile Hidden Markov Model-based homology search has been
      widely used in protein domain analysis in many different species. In particular,
      with the fast accumulation of transcriptomic data of non-model species and
      metagenomic data, profile homology search is widely adopted in integrated
      pipelines for functional analysis. While the state-of-the-art tool HMMER has
      achieved high sensitivity and accuracy in domain annotation, the sensitivity of
      HMMER on short reads declines rapidly. The low sensitivity on short read homology
      search can lead to inaccurate domain composition and abundance computation. Our
      experimental results showed that half of the reads were missed by HMMER for a RNA
      Seq dataset. Thus, there is a need for better methods to improve the homology
      search performance for short reads. RESULTS: We introduce a profile homology
      search tool named Short-Pair that is designed for short paired-end reads. By
      using an approximate Bayesian approach employing distribution of fragment lengths
      and alignment scores, Short-Pair can retrieve the missing end and determine true
      domains. In particular, Short-Pair increases the accuracy in aligning short reads
      that are part of remote homologs. We applied Short-Pair to a RNA-Seq dataset and
      a metagenomic dataset and quantified its sensitivity and accuracy on homology
      search. The experimental results show that Short-Pair can achieve better overall
      performance than the state-of-the-art methodology of profile homology search.
      CONCLUSIONS: Short-Pair is best used for next-generation sequencing (NGS) data
      that lack reference genomes. It provides a complementary paired-end read homology
      search tool to HMMER. The source code is freely available at
      https://sourceforge.net/projects/short-pair/ .

PMID- 29072141
TI  - Inferring transposons activity chronology by TRANScendence - TEs database and de
      novo mining tool.
AB  - BACKGROUND: The constant progress in sequencing technology leads to ever
      increasing amounts of genomic data. In the light of current evidence transposable
      elements (TEs for short) are becoming useful tools for learning about the
      evolution of host genome. Therefore the software for genome-wide detection and
      analysis of TEs is of great interest. RESULTS: Here we describe the computational
      tool for mining, classifying and storing TEs from newly sequenced genomes. This
      is an online, web-based, user-friendly service, enabling users to upload their
      own genomic data, and perform de-novo searches for TEs. The detected TEs are
      automatically analyzed, compared to reference databases, annotated, clustered
      into families, and stored in TEs repository. Also, the genome-wide nesting
      structure of found elements are detected and analyzed by new method for inferring
      evolutionary history of TEs. We illustrate the functionality of our tool by
      performing a full-scale analyses of TE landscape in Medicago truncatula genome.
      CONCLUSIONS: TRANScendence is an effective tool for the de-novo annotation and
      classification of transposable elements in newly-acquired genomes. Its
      streamlined interface makes it well-suited for evolutionary studies.

PMID- 29072142
TI  - MegaGTA: a sensitive and accurate metagenomic gene-targeted assembler using
      iterative de Bruijn graphs.
AB  - BACKGROUND: The recent release of the gene-targeted metagenomics assembler Xander
      has demonstrated that using the trained Hidden Markov Model (HMM) to guide the
      traversal of de Bruijn graph gives obvious advantage over other assembly methods.
      Xander, as a pilot study, indeed has a lot of room for improvement. Apart from
      its slow speed, Xander uses only 1 k-mer size for graph construction and whatever
      choice of k will compromise either sensitivity or accuracy. Xander uses a Bloom
      filter representation of de Bruijn graph to achieve a lower memory footprint.
      Bloom filters bring in false positives, and it is not clear how this would impact
      the quality of assembly. Xander does not keep track of the multiplicity of k
      mers, which would have been an effective way to differentiate between erroneous k
      mers and correct k-mers. RESULTS: In this paper, we present a new gene-targeted
      assembler MegaGTA, which attempts to improve Xander in different aspects. Quality
      wise, it utilizes iterative de Bruijn graphs to take full advantage of multiple k
      mer sizes to make the best of both sensitivity and accuracy. Computation-wise, it
      employs succinct de Bruijn graphs (SdBG) to achieve low memory footprint and high
      speed (the latter is benefited from a highly efficient parallel algorithm for
      constructing SdBG). Unlike Bloom filters, an SdBG is an exact representation of a
      de Bruijn graph. It enables MegaGTA to avoid false-positive contigs and to easily
      incorporate the multiplicity of k-mers for building better HMM model. We have
      compared MegaGTA and Xander on an HMP-defined mock metagenomic dataset, and
      showed that MegaGTA excelled in both sensitivity and accuracy. On a large
      rhizosphere soil metagenomic sample (327Gbp), MegaGTA produced 9.7-19.3% more
      contigs than Xander, and these contigs were assigned to 10-25% more gene
      references. In our experiments, MegaGTA, depending on the number of k-mers used,
      is two to ten times faster than Xander. CONCLUSION: MegaGTA improves on the
      algorithm of Xander and achieves higher sensitivity, accuracy and speed.
      Moreover, it is capable of assembling gene sequences from ultra-large metagenomic
      datasets. Its source code is freely available at https://github.com/HKU
      BAL/megagta .

PMID- 29072143
TI  - Detecting large deletions at base pair level by combining split read and paired
      read data.
AB  - BACKGROUND: Genomic structural variants (SV) play a significant role in the onset
      and progression of cancer. Genomic deletions can create oncogenic fusion genes or
      cause the loss of tumor suppressing gene function which can lead to tumorigenesis
      by downregulating these genes. Detecting these variants has clinical importance
      in the treatment of diseases. Furthermore, it is also clinically important to
      detect their breakpoint boundaries at high resolution. We have generalized the
      framework of a previously-published algorithm that located translocations, and we
      have applied that framework to develop a method to locate deletions at base pair
      level using next-generation sequencing data. Our method uses abnormally mapped
      read pairs, and then subsequently maps split reads to identify precise
      breakpoints. RESULTS: On a primary prostate cancer dataset and a simulated
      dataset, our method predicted the number, type, and breakpoints of biologically
      validated SVs at high accuracy. It also outperformed two existing algorithms on
      precise breakpoint prediction, which is clinically important. CONCLUSION: Our
      algorithm, called Pegasus, accurately calls deletion breakpoints. However, the
      method must be extended to allow for germline variant filtering and heterozygous
      deletion detection. The source code that implements Pegasus can be downloaded
      from the following URL: http://github.com/mhayes20/Pegasus .

PMID- 29072144
TI  - A new method for enhancer prediction based on deep belief network.
AB  - BACKGROUND: Studies have shown that enhancers are significant regulatory elements
      to play crucial roles in gene expression regulation. Since enhancers are
      unrelated to the orientation and distance to their target genes, it is a
      challenging mission for scholars and researchers to accurately predicting distal
      enhancers. In the past years, with the high-throughout ChiP-seq technologies
      development, several computational techniques emerge to predict enhancers using
      epigenetic or genomic features. Nevertheless, the inconsistency of computational
      models across different cell-lines and the unsatisfactory prediction performance
      call for further research in this area. RESULTS: Here, we propose a new Deep
      Belief Network (DBN) based computational method for enhancer prediction, which is
      called EnhancerDBN. This method combines diverse features, composed of DNA
      sequence compositional features, DNA methylation and histone modifications. Our
      computational results indicate that 1) EnhancerDBN outperforms 13 existing
      methods in prediction, and 2) GC content and DNA methylation can serve as
      relevant features for enhancer prediction. CONCLUSION: Deep learning is effective
      in boosting the performance of enhancer prediction.

PMID- 29072145
TI  - DCJ-RNA - double cut and join for RNA secondary structures.
AB  - BACKGROUND: Genome rearrangements are essential processes for evolution and are
      responsible for existing varieties of genome architectures. Many studies have
      been conducted to obtain an algorithm that identifies the minimum number of
      inversions that are necessary to transform one genome into another; this allows
      for genome sequence representation in polynomial time. Studies have not been
      conducted on the topic of rearranging a genome when it is represented as a
      secondary structure. Unlike sequences, the secondary structure preserves the
      functionality of the genome. Sequences can be different, but they all share the
      same structure and, therefore, the same functionality. RESULTS: This paper
      proposes a double cut and join for RNA secondary structures (DCJ-RNA) algorithm.
      This algorithm allows for the description of evolutionary scenarios that are
      based on secondary structures rather than sequences. The main aim of this paper
      is to suggest an efficient algorithm that can help researchers compare two
      ribonucleic acid (RNA) secondary structures based on rearrangement operations.
      The results, which are based on real datasets, show that the algorithm is able to
      count the minimum number of rearrangement operations, as well as to report an
      optimum scenario that can increase the similarity between the two structures.
      CONCLUSION: The algorithm calculates the distance between structures and reports
      a scenario based on the minimum rearrangement operations required to make the
      given structure similar to the other. DCJ-RNA can also be used to measure the
      distance between the two structures. This can help identify the common
      functionalities between different species.

PMID- 29072146
TI  - VAliBS: a visual aligner for bisulfite sequences.
AB  - BACKGROUND: Methylation is a common modification of DNA. It has been a very
      important and hot topic to study the correlation between methylation and diseases
      in medical science. Because of the special process with bisulfite treatment,
      traditional mapping tools do not work well with such methylation experimental
      reads. Traditional aligners are not designed for mapping bisulfite-treated reads,
      where the un-methylated 'C's are converted to 'T's. RESULTS: In this paper, we
      develop a reliable and visual tool, named VAliBS, for mapping bisulfate sequences
      to a genome reference. VAliBS works well even on large scale data or high noise
      data. By comparing with other state-of-the-art tools (BisMark, BSMAP, BS
      Seeker2), VAliBS can improve the accuracy of bisulfite mapping. Moreover, VAliBS
      is a visual tool which makes its operations more easily and the alignment results
      are shown with colored marks which makes it easier to be read. VAliBS provides
      fast and accurate mapping of bisulfite-converted reads, and a friendly window
      system to visualize the detail of mapping of each read. CONCLUSIONS: VAliBS works
      well on both simulated data and real data. It can be useful in DNA methylation
      research. VALiBS implements an X-Window user interface where the methylation
      positions are visual and the operations are friendly.

PMID- 29072147
TI  - Tractable RNA-ligand interaction kinetics.
AB  - BACKGROUND: The binding of small ligands to RNA elements can cause substantial
      changes in the RNA structure. This constitutes an important, fast-acting
      mechanism of ligand-controlled transcriptional and translational gene regulation
      implemented by a wide variety of riboswitches. The associated refolding processes
      often cannot be explained by thermodynamic effects alone. Instead, they are
      governed by the kinetics of RNA folding. While the computational analysis of RNA
      folding can make use of well-established models of the thermodynamics of RNA
      structures formation, RNA-RNA interaction, and RNA-ligand interaction, kinetic
      effects pose fundamentally more challenging problems due to the enormous size of
      the conformation space. The analysis of the combined process of ligand binding
      and structure formation even for small RNAs is plagued by intractably large state
      spaces. Moreover, the interaction is concentration-dependent and thus is
      intrinsically non-linear. This precludes the direct transfer of the strategies
      previously used for the analysis of RNA folding kinetics. RESULTS: In our novel,
      computationally tractable approach to RNA-ligand kinetics, we overcome the two
      main difficulties by applying a gradient-based coarse graining to RNA-ligand
      systems and solving the process in a pseudo-first order approximation. The latter
      is well-justified for the most common case of ligand excess in RNA-ligand
      systems. We present the approach rigorously and discuss the parametrization of
      the model based on empirical data. The method supports the kinetic study of RNA
      ligand systems, in particular at different ligand concentrations. As an example,
      we apply our approach to analyze the concentration dependence of the ligand
      response of the rationally designed, artificial theophylline riboswitch RS3.
      CONCLUSION: This work demonstrates the tractability of the computational analysis
      of RNA-ligand interaction. Naturally, the model will profit as more accurate
      measurements of folding and binding parameters become available. Due to this
      work, computational analysis is available to support tasks like the design of
      riboswitches; our analysis of RS3 suggests strong co-transcriptional effects for
      this riboswitch. The method used in this study is available online, cf. Section
      "Availability of data and materials".

PMID- 29072148
TI  - Patient-family EoL communication and its predictors: Reports from caregivers of
      Latino patients in the rural U.S.-Mexico border region.
AB  - OBJECTIVE: Family caregivers play an important role in end-of-life (EoL) decision
      making when the patient is unable to make his/her own decisions. While
      communication about EoL care between patients and family is perhaps a first step
      toward advance care planning (ACP)/EoL decisions, not every culture puts great
      value on open communication about this topic. The aims of the present study were
      to explore EoL communication and the aspects of communication among caregivers of
      Latino patients in the rural United States (U.S.)-Mexico border region. METHOD:
      This study analyzed data from a hospice needs assessment collected from 189
      family caregivers of Latino patients at a home health agency in a rural U.S.
      Mexico border region. Bivariate tests and logistic regression were used to
      address our aims. RESULTS: About half of the family caregivers (n = 96, 50.8%)
      reported to have ever engaged in EoL discussion with patients. Significant
      predictors of EoL discussion included life-sustaining treatment preference (odds
      ratio [OR] = 0.44, p < 0.05); knowledge of an advance directive (AD) (OR = 5.50,
      p < 0.01); and distrust of physicians (OR = 0.29, p < 0.01). Caregivers who
      preferred extending the life of their loved one even if he/she had to rely on
      life supports were less likely to engage in EoL communication. Also, caregivers
      who worried that physicians might want to stop treatments (i.e., "pull the plug")
      too soon were less likely to do so. Conversely, caregivers who had knowledge
      about ADs were more likely to engage in EoL communication. SIGNIFICANCE OF
      RESULTS: EoL communication is a complex process influenced by individual, social,
      and cultural values and the beliefs of both the patient and his/her family.
      Inclusion of family caregivers in the ACP process and facilitating culturally
      tailored EoL communication between patients and family caregivers is important.

PMID- 29072149
TI  - Pattern of Changes during Treatment: A Comparison between a Positive Psychology
      Intervention and a Cognitive Behavioral Treatment for Clinical Depression.
AB  - Research on psychotherapy has traditionally focused on analyzing changes between
      the beginning and the end of a treatment. Few studies have addressed the pattern
      of therapeutic change during treatment. The aim of this study was to examine the
      pattern of changes in clinical and well-being variables during a cognitive
      behavioral therapy (CBT) program compared with an integrative positive psychology
      interventions program for clinical depression IPPI-D. 128 women with a diagnosis
      of major depression or dysthymia were assigned to the CBT or PPI group. A measure
      of depressive symptoms (i.e., Beck Depression Inventory) and well-being (i.e.,
      Pemberton Happiness Index) were administered four times: at the beginning and end
      of the treatment, as well as during treatment (at sessions 4 and 7). Through
      mixed-model repeated measures ANOVAs, both depressive symptoms (p .08). The
      percentage of improvement in depressive symptoms in the first treatment period
      was higher than in the later ones (ps < .005). On the contrary, well-being showed
      a more gradual improvement (p = .15). These results highlight the importance of
      assessing the pattern of changes in symptoms and well-being separately.

PMID- 29072150
TI  - Evaluating the Relationship Between Hospital Antibiotic Use and Antibiotic
      Resistance in Common Nosocomial Pathogens.
AB  - OBJECTIVE The relationship between hospital antibiotic use and antibiotic
      resistance is poorly understood. We evaluated the association between antibiotic
      utilization and resistance in academic and community hospitals in Ontario,
      Canada. METHODS We conducted a multicenter observational ecological study of 37
      hospitals in 2014. Hospital antibiotic purchasing data were used as an indicator
      of antibiotic use, whereas antibiotic resistance data were extracted from
      hospital indexes of resistance. Multivariate regression was performed, with
      antibiotic susceptibility as the primary outcome, antibiotic consumption as the
      main predictor, and additional covariates of interest (ie, hospital type,
      laboratory standards, and patient days). RESULTS With resistance data
      representing more than 90,000 isolates, we found the increased antibiotic
      consumption in defined daily doses per 1,000 patient days (DDDs/1,000 PD) was
      associated with decreased antibiotic susceptibility for Pseudomonas aeruginosa (
      0.162% per DDD/1,000 PD; P=.119). However, increased antibiotic consumption
      predicted increased antibiotic susceptibility significantly for Escherichia coli
      (0.173% per DDD/1,000 PD; P=.005), Klebsiella spp (0.124% per DDD/1,000 PD;
      P=.004), Enterobacter spp (0.194% per DDD/1,000 PD; P=.003), and Enterococcus spp
      (0.309% per DDD/1,000 PD; P=.001), and nonsignificantly for Staphylococcus aureus
      (0.012% per DDD/1,000 PD; P=.878). Hospital type (P=.797) and laboratory standard
      (P=.394) did not significantly predict antibiotic susceptibility, while increased
      hospital patient days generally predicted increased organism susceptibility
      (0.728% per 10,000 PD; P<.001). CONCLUSIONS We found that hospital-specific
      antibiotic usage was generally associated with increased, rather than decreased
      hospital antibiotic susceptibility. These findings may be explained by community
      origins for many hospital-diagnosed infections and practitioners choosing agents
      based on local antibiotic resistance patterns. Infect Control Hosp Epidemiol
      2017;38:1457-1463.

PMID- 29072151
TI  - Examining Facets of Depression and Social Anxiety: The Relation among Lack of
      Positive Affect, Negative Cognitions, and Emotion Dysregulation.
AB  - Depression and Social Anxiety Disorder are commonly conceptualized by the
      presence of negative affect. However, these disorders are also characterized by
      lack of positive affect, presence of negative cognitions, and emotion
      dysregulation which may play an important role in the onset and maintenance of
      these disorders. The present study explored differences among these variables in
      189 clinical patients diagnosed with Major Depression, Social Anxiety Disorder,
      or both. Results showed differences in lack of positivity F(2, 185) = 18.92, p =
      .0001, eta2 = .17, presence of negative cognitions F(2, 185) = 13.97, p = .0001,
      eta2 = .13, and the use of rumination F(2, 185) = 14.63, p = .0001, eta2 = .14
      and punishment F(2, 181) = 7.64, p = .001, eta2 = .08 among groups. Overall, lack
      of positivity, negative cognitions, and emotion dysregulation were elevated in
      the comorbid group, whereas lack of positivity and negative cognitions were
      specifically found for patients diagnosed with depression compared to socially
      anxious patients. In addition, the study examined the relation of both, lack of
      positivity and negative cognitions, to emotion regulation processes among groups.
      Overall, lack of positivity was associated with fear and avoidance in the social
      anxiety group (all r > .417, p .370, p < .01). Limitations of the present study
      and future directions are discussed.

PMID- 29072152
TI  - Why the concept of schizophrenia is still alive and kicking.

PMID- 29072153
TI  - Sources of bias in Gorman critique of bias: again a need for more reasonable,
      valid conclusions with true dialogue.

PMID- 29072154
TI  - Where are the low-calorie sweeteners? An analysis of the presence and types of
      low-calorie sweeteners in packaged foods sold in Brazil from food labelling.
AB  - OBJECTIVE: Studies have shown that consumption of low-calorie sweeteners (LCS)
      may be associated with harmful health effects. The current study investigated the
      presence and types of LCS added to packaged foods. DESIGN: Cross-sectional study
      analysing the presence and types of LCS in the ingredients lists of packaged
      foods sold at a major Brazilian supermarket. To identify types of LCS allowed for
      use in foods in Brazil, current legislation was consulted. Data were organised
      and analysed through descriptive statistics, presenting simple and relative
      frequencies of LCS presence categorised by food group. SETTING: Supermarket in
      Florianopolis, southern Brazil. SUBJECTS: Packaged food products (n 4539) from
      eight food groups. RESULTS: One or more LCS were found in 602 (13.3 %) of the
      packaged foods analysed. There were 1329 citations of LCS among these foods, with
      a mean of 2.2 sweeteners per food. Groups with the highest frequency of foods
      containing LCS were: products with energy derived from carbohydrates and fats
      (25.0 %); milk and dairy products (11.7 %); bakery products, cereals, legumes,
      roots and tubers (11.2 %); and fruits, juices, nectars and fruit drinks (8.3 %).
      CONCLUSIONS: There was high prevalence of packaged foods with LCS, especially in
      food groups that form the basis of the Brazilian diet. The study was the first to
      extensively analyse the presence and types of LCS in packaged foods available for
      sale in a Brazilian supermarket and can be useful to monitor the use of LCS in
      these foods, as well as to support future changes in legislation to label sugars.

PMID- 29072155
TI  - Alive but not well: the limited validity but continued utility of the concept of
      schizophrenia.
AB  - Guloksuz & van Os boldly challenge the status quo as pertains to schizophrenia.
      In 'The Slow Death of the Concept of Schizophrenia, and the Painful Birth of the
      Psychosis Spectrum' (Guloksuz & van Os, 2017) they thoughtfully review long
      standing concerns about this diagnostic category and present a new
      conceptualization. The authors question the validity of the schizophrenia concept
      citing variable clinical outcomes, transdiagnostic manifestations of psychosis,
      and the difficulty in identifying biomarkers, among other concerns. They also
      point toward the over-representation of schizophrenia in the psychosis literature
      and lament that patients and clinicians have come to associate this illness with
      predominantly poor outcomes. Finally, they propose removing the diagnosis of
      schizophrenia from the diagnostic nomenclature and instituting a broad new
      classification system, 'psychosis spectrum disorder' (PSD), to capture the many
      manifestations of psychosis. In this commentary, we advise against the
      institution of a psychosis spectrum due to the potential negative effects this
      framework would have on clinical care and progress in biological research.

PMID- 29072156
TI  - Positive Technologies for Understanding and Promoting Positive Emotions.
AB  - Information and Communication Technologies (ICTs) have become increasingly
      present in our lives, and their use has spread considerably. This paper presents
      a review of the way ICTs can help practitioners and researchers to study,
      promote, and train positive emotions. It is framed within the field of Positive
      Technologies: the applied scientific approach to the study of the use of
      technology to improve the quality of personal experience, with the goal of
      increasing wellbeing. First, the article presents an introduction to the topic of
      technologies and positive emotions. Then, it describes how ICTs can aid in
      monitoring, assessing, promoting, modifying, and training positive emotions.
      Finally, implications and future directions of the role of Positive Technologies
      in positive emotions are discussed. The authors conclude that, in the near
      future, Positive Technologies and the field of positive emotions will interact
      synergistically, producing an exponential growth in the understanding and
      promotion of positive emotions.

PMID- 29072157
TI  - The Study of the Antisaccade Performance and Contingent Negative Variation
      Characteristics in First-Episode and Chronic Schizophrenia Patients.
AB  - The study tested whether the antisaccade (AS) performance and Contingent Negative
      Variation (CNV) measures differed between the first-episode and chronic patients
      to provide the evidence of PFC progressive functional deterioration. Subjects
      included 15 first-episode and 20 chronic schizophrenic patients (with the
      duration of illness more than 5 years), and 21 control subjects. The first
      episode and chronic patients had significantly elevated error percent (p < .05,
      effect size 1.10 and p < .001, effect size 1.25), increased AS latencies (p <
      .01, effect size 1.18 and p < .001, effect size 1.69), and increased latencies
      variability (p < .01, effect size 1.52 and p < .001, effect size 1.37) compared
      to controls. Chronic patients had marginally significant increase of the response
      latency (p = .086, effect size .78) and latency variability (p < .099, effect
      size .63) compared to first-episode ones. Results of CNV analysis revealed that
      chronic patients only exhibited robustly declined frontal CNV amplitude at Fz (p
      < .05, effect size .70), F3 (p < .05, effect size .88), and F4 (p < .05, effect
      size .71) sites compared to controls. The obtained results might be related to
      specific changes in prefrontal cortex function over the course of schizophrenia.

PMID- 29072158
TI  - Technology in dietary assessment.

PMID- 29072159
TI  - A Question of Control? Examining the Role of Control Conditions in Experimental
      Psychopathology using the Example of Cognitive Bias Modification Research.
AB  - While control conditions are vitally important in research, selecting the optimal
      control condition can be challenging. Problems are likely to arise when the
      choice of control condition is not tightly guided by the specific question that a
      given study aims to address. Such problems have become increasingly apparent in
      experimental psychopathology research investigating the experimental modification
      of cognitive biases, particularly as the focus of this research has shifted from
      theoretical questions concerning mechanistic aspects of the association between
      cognitive bias and emotional vulnerability, to questions that instead concern the
      clinical efficacy of 'cognitive bias modification' (CBM) procedures. We discuss
      the kinds of control conditions that have typically been employed in CBM
      research, illustrating how difficulties can arise when changes in the types of
      research questions asked are not accompanied by changes in the control conditions
      employed. Crucially, claims made on the basis of comparing active and control
      conditions within CBM studies should be restricted to those conclusions allowed
      by the specific control condition employed. CBM studies aiming to establish
      clinical utility are likely to require quite different control conditions from
      CBM studies aiming to illuminate mechanisms. Further, conclusions concerning the
      clinical utility of CBM interventions cannot necessarily be drawn from studies in
      which the control condition has been chosen to answer questions concerning
      mechanisms. Appreciating the need to appropriately alter control conditions in
      the transition from basic mechanisms-focussed investigations to applied clinical
      research could greatly facilitate the translational process.

PMID- 29072160
TI  - Defining the location of promoter-associated R-loops at near-nucleotide
      resolution using bisDRIP-seq.
AB  - R-loops are features of chromatin consisting of a strand of DNA hybridized to
      RNA, as well as the expelled complementary DNA strand. R-loops are enriched at
      promoters where they have recently been shown to have important roles in
      modifying gene expression. However, the location of promoter-associated R-loops
      and the genomic domains they perturb to modify gene expression remain unclear. To
      resolve this issue, we developed a bisulfite-based approach, bisDRIP-seq, to map
      R-loops across the genome at near-nucleotide resolution in MCF-7 cells. We found
      the location of promoter-associated R-loops is dependent on the presence of
      introns. In intron-containing genes, R-loops are bounded between the
      transcription start site and the first exon-intron junction. In intronless genes,
      the 3' boundary displays gene-specific heterogeneity. Moreover, intronless genes
      are often associated with promoter-associated R-loop formation. Together, these
      studies provide a high-resolution map of R-loops and identify gene structure as a
      critical determinant of R-loop formation.

PMID- 29072162
TI  - Impact of homogenization of pasteurized human milk on gastric digestion in the
      preterm infant: A randomized controlled trial.
AB  - BACKGROUND & AIMS: It has been suggested that homogenization of Holder
      pasteurized human milk (PHM) could improve fat absorption and weight gain in
      preterm infants, but the impact on the PHM digestive kinetics has never been
      studied. Our objective was to determine the impact of PHM homogenization on
      gastric digestion in preterm infants. METHODS: In a randomized controlled trial,
      eight hospitalized tube-fed preterm infants were their own control to compare the
      gastric digestion of PHM and of homogenized PHM (PHHM). PHM was obtained from
      donors and, for half of it, was homogenized by ultrasonication. Over a six-day
      sequence, gastric aspirates were collected twice a day, before and 35, 60 or 90
      min after the start of PHM or PHHM ingestion. The impact of homogenization on PHM
      digestive kinetics and disintegration was tested using a general linear mixed
      model. Results were expressed as means +/- SD. RESULTS: Homogenization leaded to
      a six-fold increase in the specific surface (P < 0.01) of lipid droplets. The
      types of aggregates formed during digestion were different between PHM and PHHM,
      but the lipid fraction kept its initial structure all over the gastric digestion
      (native globules in PHM vs. blend of droplets in PHHM). Homogenization increased
      the gastric lipolysis level (P < 0.01), particularly at 35 and 60 min (22 and 24%
      higher for PHHM, respectively). Homogenization enhanced the proteolysis of serum
      albumin (P < 0.05) and reduced the meal emptying rate (P < 0.001, half-time
      estimated at 30 min for PHM and 38 min for PHHM). The postprandial gastric pH was
      not affected (4.7 +/- 0.9 at 90 min). CONCLUSIONS: Homogenization of PHM
      increased the gastric lipolysis level. This could be a potential strategy to
      improve fat absorption, and thus growth and development in infants fed with PHM;
      however, its gastrointestinal tolerance needs to be investigated further. This
      trial was registered at clinicaltrials.gov as NCT02112331.

PMID- 29072161
TI  - Identification and functional characterization of muscle satellite cells in
      Drosophila.
AB  - Work on genetic model systems such as Drosophila and mouse has shown that the
      fundamental mechanisms of myogenesis are remarkably similar in vertebrates and
      invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells
      that are essential for the regeneration of damaged muscles in vertebrates, have
      not been reported in invertebrates. In this study, we show that lineal
      descendants of muscle stem cells are present in adult muscle of Drosophila as
      small, unfused cells observed at the surface and in close proximity to the mature
      muscle fibers. Normally quiescent, following muscle fiber injury, we show that
      these cells express Zfh1 and engage in Notch-Delta-dependent proliferative
      activity and generate lineal descendant populations, which fuse with the injured
      muscle fiber. In view of strikingly similar morphological and functional
      features, we consider these novel cells to be the Drosophila equivalent of
      vertebrate muscle satellite cells.

PMID- 29072163
TI  - Effect of high and low glycemic index breakfast on postprandial metabolic
      parameters and satiety in subjects with type 2 diabetes mellitus under intensive
      insulin therapy: Controlled clinical trial.
AB  - BACKGROUND AND AIM: The results of studies evaluating the metabolic effects of
      glycemic index (GI) in subjects with type 2 diabetes mellitus (DM2) have been
      contradictory. Consequently, the benefits of its application are controversial
      and polarized opinions of international organizations have been disclosed. The
      above situation leads this study to evaluate the acute effect of low and high GI
      breakfast on the glycemic response and satiety in subjects with DM2 under
      intensive insulin therapy (IIT). METHODS: A controlled, crossover and single
      blind clinical trial was developed involving 10 obese subjects with DM2 under
      IIT, with a period of at least six months under IIT and with fast insulin
      prescription before breakfast. Subjects ingested on two different occasions a
      high or low GI breakfast. In both stages, glycemia was evaluated at 0 (basal),
      30, 60 and 120 min, and satiety and satiation were evaluated through a visual
      analogue scale. RESULTS: In contrast to high GI breakfast, the low GI meal
      generated a significant decrease of 46% for the area under the curve of glucose
      (Delta 1940 mg/dL * 120 min, p = 0.022) and in mean glycemia evaluated at 30, 60
      and 120 min. Moreover, in the low GI stage 8 of 10 patients achieved a 2 h
      postprandial glycemia lower than 180 mg/dL, without statistical significance. A
      nonsignificant increase of 12.7% (Delta 1.06 cm, p = 0.271) in satiety at 120 min
      in the low GI stage was observed. CONCLUSION: In contrast to high GI breakfast,
      the low GI breakfast generated a significantly lower glycemic response. This
      assay allowed for the contribution of more in depth nutritional recommendations
      for this group of patients. Registered under ClinicalTrials.gov Identifier no.
      NCT02881164.

PMID- 29072165
TI  - Therapeutic effect of vitamin D in acute lower respiratory infection: A
      randomized controlled trial.
AB  - OBJECTIVES: To study the effect of vitamin D supplementation on the outcome of
      acute lower respiratory infection in hospitalized children. STUDY DESIGN: This is
      an open label parallel group randomized trial. Total of 154 children aged 2 mo-5
      yrs (mean age 13 mo) admitted with acute lower respiratory infection (ALRI) were
      randomized to receive standard care therapy alone or standard care therapy for
      the respiratory infection along with a single oral dose of 100,000 IU of vitamin
      D3. Serum 25(OH)D levels were measured at admission in all the children and 72 h
      after administration of vitamin D in the supplemented group. Primary outcome
      measured was the duration of hospital stay. Secondary outcomes measured were
      mortality, incidence of complications, admission to PICU and recurrence of
      respiratory infections within 90 days of discharge. Primary outcome was compared
      using Mann Whitney U test and secondary outcomes were compared using chi-square
      or Fischer's exact test. RESULTS: Baseline characteristics were comparable
      between the two groups. There was no statistically significant difference in the
      primary outcome (Median duration of hospital stay in both the groups) and also in
      secondary outcomes (mortality, PICU admission, complications and recurrence of
      respiratory infections within 90 days of discharge). CONCLUSION: Single oral dose
      of 100,000 IU of vitamin D3 did not lead to reduction in duration of hospital
      stay, mortality, PICU admission or complications related to ALRI when compared to
      standard therapy alone in under five children hospitalized with ALRI but was able
      to achieve serum vitamin D sufficiency within 72 h of administration. Registered
      under clinical trial Registry of India Identifier no: CTRI/2014/09/005032.

PMID- 29072164
TI  - Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid
      profiles, growth and morbidities in extremely premature infants: A randomized
      controlled trial.
AB  - BACKGROUND & AIMS: The purpose of the study was to compare the effects of the
      parenteral emulsion SMOFlipid(r), with 15% fish oil, with Clinoleic(r) on
      retinopathy of prematurity (ROP) and other morbidities and growth, and to compare
      their impact on longitudinal serum levels of fatty acids. Retinopathy of
      prematurity, other morbidity and growth were correlated with each parenteral
      lipid supplement. METHODS: Ninety infants born at gestational age <28 weeks were
      randomized to treatment with SMOFlipid(r) or Clinoleic(r). Two thirds (66%) of
      the infants received parenteral nutrition for up to 14 days birth (median 8,
      range 2-14 days), and additional 25% of the infants received for up to 28 days
      after birth (median 21, range 15-28 days). Cord blood samples and then venous
      blood samples were obtained at ages 1, 7, 14, and 28 days and at postmenstrual
      age (PMA) 32, 36, and 40 weeks. Breastmilk was collected at postnatal day 7, and
      at PMA 32 and 40 weeks. Serum phospholipid and breastmilk total fatty acids were
      analyzed by gas chromatography-mass spectrometry. Treatment groups were compared
      with regard to ROP, bronchopulmonary dysplasia, necrotizing enterocolitis, patent
      ductus arteriosus sepsis and growth between birth and 36 weeks. RESULTS: Infants
      on SMOFlipid(r) had higher fractions of omega-3 LCPUFA eicosapentaenoic acid
      (EPA) and slightly higher omega-3 LCPUFA docosahexaenoic acid (DHA) fraction and
      a decreased arachidonic acid (AA) to DHA ratio from one week after birth up to 32
      postmenstrual weeks compared to infants on Clinoleic(r). Treatment groups did not
      differ in morbidities or growth. CONCLUSION: Supplementation with SMOFlipid(r)
      containing 15% fish oil during parenteral nutrition increased EPA substantially,
      DHA marginally, reduced AA and decreased AA to DHA ratio. It did not reduce
      morbidity or affect growth. Since extremely preterm infants accumulate a large
      deficit of DHA and AA, studies on more prolonged or different levels of DHA and
      AA supplementation are warranted.

PMID- 29072166
TI  - Effect of an intradialytic protein-rich meal intake in nutritional and body
      composition parameters on hemodialysis patients.
AB  - BACKGROUND AND AIMS: Protein intake is a key point to maintain an adequate
      nutritional status in hemodialysis (HD) patients. There are some studies that
      confirm the positive influence of intradialytic oral nutritional supplementation
      in several nutritional parameters in HD patients. The aim of this study was to
      evaluate the effect of an intradialytic protein rich meal in nutritional and body
      composition parameters on HD patients. METHODS: This was a 6-months single center
      non-randomized study with 99 patients in HD from one Nephrocare dialysis unit in
      Portugal. Patients in the intervention group (IG) presented one albumin value <=
      3.8 g/dL in the two measurements prior to the beginning of the study. The IG ate
      a protein rich meal during each treatment. The control group (CG) continued to
      eat their usual snack brought from home. Albumin, nPCR, potassium, phosphorus, C
      reactive protein (CRP), dry weight and body composition were measured at baseline
      and at the end of the study. RESULTS: Patient's mean age was 69.9 +/- 12.9 years
      and HD vintage, 60.0 +/- 50.5 months. Both groups were similar at the start of
      the study, except in albumin (p = 0.019). After the intervention, protein intake
      increased in the IG (p = 0.001). Albumin decreased in both groups but this
      difference was higher and only statistically significant in the CG (p = 0.039).
      Regarding body composition, in the CG, the fat tissue index (FTI) (p = 0.022) and
      the lean tissue index (LTI) (p = 0.003) diminished after the 6 months of the
      follow-up. However, in the IG the LTI value also reduced (p = 0.008) but FTI
      increased (p = <0.001) at the end of the study. There were no statistically
      significant differences on dry weight, potassium, phosphorus, and CRP.
      CONCLUSION: Apart from the effect on protein intake, the importance of this study
      relies on the positive changes in regard to patient's body composition obtained
      after 6 months of an intradialytic intake of a protein rich meal during the HD
      treatment. This type of intervention can contribute to ameliorate patient's
      nutritional status without a negative effect on other parameters.

PMID- 29072167
TI  - Effect of whey protein supplementation on long and short term appetite: A meta
      analysis of randomized controlled trials.
AB  - Specific components of dairy, such as whey proteins may have beneficial effects
      on body composition by suppressing appetite, although the findings of existing
      studies have been inconsistent. Therefore, a meta-analysis of randomized
      controlled trials was performed to investigate effect of whey protein
      supplementation on long and short term appetite. A systematic search was
      conducted to identify eligible publications. Means and SDs for hunger, fullness,
      satiety, desire to eat and prospective consumption of food, before and after
      intervention, were extracted and then composite appetite score (CAS) calculated.
      To pool data, either a fixed-effects model or a random-effects model and for
      assessing heterogeneity, Cochran's Q and I2 tests were used. Eight publications
      met inclusion criteria that 5 records were on short term and 3 records on long
      term appetite. The meta-analysis showed a significant reduction in long term
      appetite by 4.13 mm in combined appetite score (CAS) (95% Confidence interval
      (CI): -6.57, -1.96; p = 0.001). No significant reduction in short term appetite
      was also seen (Mean difference (MD) = -0.39 95% CI = -2.07, 1.30; p = 0.653).
      Subgroup analyses by time showed that compared with carbohydrate, the reduction
      in appetite following consumption of whey consumption was not significant (MD = 
      0.39, 95% CI = -2.07, 1.3, p = 0.65, I2 = 0.0%.)A significant reduction in
      prospective food consumption was seen (MD = -2.17, 95% CI = -3.86, -0.48). The
      results of our meta-analysis showed that whey protein may reduce the long and
      short term appetite, but our finding did not show any significant difference in
      appetite reduction between whey protein and carbohydrate in short duration.

PMID- 29072168
TI  - Application of adaptive neuro-fuzzy inference systems (ANFIS) to delineate
      estradiol, glutathione and homocysteine interactions.
AB  - The rationale of the current study was to elucidate the contributing factors for
      the gender-based differences in total plasma homocysteine levels. A total of 413
      subjects comprising of 293 men and 120 women were enrolled for the study.
      Chemiluminescence technology for vitamin B12, folate and total plasma
      homocysteine; ELISA for estradiol and 8-oxo-2-deoxyguanosine; Ellman's method for
      total glutathione; and PCR-RFLP analysis for the detection of methylene
      tetrahydrofolate reductase (MTHFR) C677T polymorphism were employed. No
      statistically significant differences were observed between the men and women in
      the distribution of age (p = 0.82), vitamin B12 (p = 0.23), folate (p = 0.36) and
      MTHFR C677T polymorphism (p = 0.35). However, the total plasma homocysteine
      levels were higher in men compared to women (28.4 +/- 17.9 vs. 20.6 +/- 13.6
      MUmol/L, p < 0.0001). In order to explain this gender differences in
      homocysteine, adaptive neuro-fuzzy inference systems (ANFIS) were developed to
      understand trivariate interactions among estradiol, glutathione and homocysteine.
      In the presence of adequate estradiol levels, inverse association was observed
      between glutathione and homocysteine. This association is lost when estradiol
      levels were inadequate. Estradiol was found to quench homocysteine mediated
      oxidative DNA damage. Irrespective of gender, combined deficiency of vitamin B12
      and folate showed positive association with hyperhomocysteinemia and vice versa.
      Homocysteine reduction in response to vitamin status varied according to gender
      with men responding to folate and women responding to B12. To conclude, gender
      differences in homocysteine are attributable estradiol mediated lowering of
      homocysteine that prevents inactivation of glutathione mediated oxidative defense
      in women.

PMID- 29072169
TI  - Amnestic dementia impairment in Parkinson's disease: The role of body
      composition, ageing and insulin resistance.
AB  - BACKGROUND: The risk of cognitive impairment associated with Parkinson's disease
      (PD) is related to ageing. The role of body compartmentalization and associated
      metabolic dysfunctions, as a risk factor for dementia in PD is still not clear.
      OBJECTIVE: To investigate body mass distribution, insulin resistance, and other
      parameters in patients without dementia, and those with dementia classified as
      compromised delayed memory. SUBJECTS AND METHODS: We recorded body composition,
      basal levels of insulin resistance, and other data from 135 patients, who were
      followed for at least two years. The patients completed a Brief Cognitive Battery
      test. Patients with delayed recall memory impairment were assessed using the
      Mattis dementia rating scale. RESULTS: There was a correlation between age and
      the patient's scores. Age was negatively correlated with scores on all of the
      screening battery subtests (p <= 0.001), while formal education was positively
      correlated with the test scores. Insulin resistance was higher in non-demented
      patients compared to patients with impaired memory (p = 0.0027). There was no
      association between body composition and cognitive dysfunction in patients with
      PD. CONCLUSIONS: The results of this study indicate an apparent decrease in
      insulin resistance associated with cognitive impairment in PD. We found no
      correlations between body composition and memory dysfunction associated with PD.

PMID- 29072170
TI  - Caffeine intake and abstract reasoning among 1374 unselected men and women from
      general population. Role of the -163C>A polymorphism of CYP1A2 gene.
AB  - BACKGROUND AND AIMS: The possible effect of caffeine as an enhancer of cognitive
      performance, particularly that on abstract reasoning, has never been studied in
      an epidemiological setting, especially in relation to -163C>A polymorphism of
      CYP1A2 gene, largely controlling caffeine metabolism. Aim of this study was to
      ascertain whether in general population free chronic caffeine intake modifies
      abstract reasoning, and if this effect is influenced by the above mentioned
      genotype, by age, schooling, ethanol intake and smoking habits. METHODS: We
      studied 1374 unselected men and women aged 51 +/- 15 years (range 18-89) from a
      general population. Daily caffeine intake deriving from coffee, tea, chocolate or
      cola was calculated from an anamnestic questionnaire and from a 7-day dietary
      diary. Abstract reasoning was measured in the frame of a neuropsychological
      assessment as the ability to find a concept linking two words indicating objects
      or actions and explaining how they were connected. RESULTS: In age-schooling
      adjusted linear regression, the higher the caffeine intake, the better the
      abstraction score. Abstract reasoning depended on caffeine in the -163C>A CC
      homozygous only (so-called slow metabolizers), where it was higher in the 3rd
      tertile of caffeine intake. Age and ethanol reduced while smoking and schooling
      enhanced this association. The interaction term between caffeine and the -163C>A
      polymorphism was accepted in linear regressions. Caffeine consumption resulted
      innocuous for the A-carriers (so-called fast metabolizers). CONCLUSIONS: In
      general population, a positive association between caffeine intake and abstract
      reasoning exists in the CC homozygous of the -163C>A polymorphism of CYP1A2 gene.

PMID- 29072171
TI  - Effects of dietary omega-3 on dystrophic cardiac and diaphragm muscles as
      evaluated by 1H magnetic resonance spectroscopy: Metabolic profile and calcium
      related proteins.
AB  - BACKGROUND & AIMS: Duchenne muscular dystrophy (DMD) is characterized by the
      absence of dystrophin and muscle degeneration. Calcium dysregulation and
      oxidative stress also contribute to the disease progression. We evaluated the
      potential therapeutic benefits of supplementation with omega-3 on the metabolic
      profile, calcium-related proteins and oxidative stress response in the heart and
      diaphragm (DIA) of the mdx mouse model of DMD at later stages of the disease (13
      months). METHODS: Mdx mice (8 months old) received omega-3 via a dietary
      supplement for 5 months. Metabolites were analyzed by 1H magnetic resonance
      spectroscopy. Muscle total calcium was evaluated by inductively coupled plasma
      optical emission spectrometry. Calsequestrin, TRPC1 and 4-HNE were determined via
      Western blot. RESULTS: Omega-3 decreased the metabolites taurine (related to
      calcium regulation and oxidative stress), aspartate (related to inflammation) and
      oxypurinol (related to oxidative stress) in the heart (aspartate) and DIA
      (taurine, aspartate and oxypurinol). Omega-3 also significantly decreased total
      calcium and TRPC1 levels in cardiac and DIA muscles and increased the levels of
      calsequestrin (cardiac and skeletal) and decreased the oxidative stress marker 4
      HNE. CONCLUSIONS: The current study suggests that supplementation with omega-3
      may generate therapeutic benefits on dystrophy progression, at later stages of
      the disease, with changes in the metabolic profile that may be correlated to
      omega-3 therapy.

PMID- 29072172
TI  - Flavonoid intake and mortality from cardiovascular disease and all causes: A meta
      analysis of prospective cohort studies.
AB  - BACKGROUND AND AIMS: Accumulating studies have suggested that flavonoid intake is
      associated with a decreased risk of coronary heart disease and cardiovascular
      disease (CVD). There are many epidemiological studies on flavonoid intake and
      mortality, but no comprehensive investigation has yet been conducted. To
      quantitatively assess the association between flavonoid intake and mortality from
      CVD and all-causes, we performed a meta-analysis of prospective cohort studies.
      METHODS: Eligible studies were identified by searching PubMed and Web of Science
      databases for all articles published up to May 2016 and via hand searching. Study
      specific estimates adjusting for potential confounders were combined to calculate
      a pooled relative risk (RR) with 95% confidence interval (CI) using a random
      effects model. RESULTS: A total of 15 prospective cohort studies that examined
      the association between flavonoid intake and mortality from CVD and all-causes
      were identified. The pooled RR of CVD mortality for the highest versus lowest
      category of flavonoid intake was 0.86 (95% CI: 0.75, 0.98). By subclass of
      flavonoids, all classes, except flavonols and isoflavones, showed significant
      inverse associations. A nonlinear association was found between flavonoid intake
      and CVD mortality in the dose-response analysis. For total mortality, a high
      intake of flavonoids was associated with lower total mortality (pooled RR = 0.86,
      95% CI: 0.73, 1.00). CONCLUSIONS: Our findings indicate that a high intake of
      flavonoids is associated with reduced risk of mortality from CVD and all causes
      in men and women. These results support current recommendations of high fruit and
      vegetables intake as a part of a healthy diet.

PMID- 29072173
TI  - Ribera's depiction of the sense of taste: A case of 'gouty arthritis' resulting
      from overindulgence?
AB  - Jusepe de Ribera's seventeenth-century painting devoted to the sense of taste,
      part of a series on the five senses, depicts a man from one of 'the humbler walks
      of life' enjoying his meal. The redness of the man's cheeks and nose, and the
      swollen index finger on his left hand, are discussed in relation to the food and
      drink shown in the painting. It is suggested that the man's high purine intake
      combined with a substantial quantity of alcohol supports the hypothesis that the
      swollen finger is affected by gout, which was traditionally considered a
      'patrician disease'. Ribera's portrayal of a well-fed but non-patrician figure
      with gouty arthritis of the finger may have been intended as a warning against
      overindulgence and gluttony at all levels of society.

PMID- 29072174
TI  - Blood lipid tests in 2017.
AB  - Strong epidemiological evidence supports a causal relationship between
      dyslipidemia and atherosclerotic cardio-vascular disease, which remains the
      leading cause of death and morbidity worldwide. A lipid profile (total
      cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides) is recommended at
      the initial evaluation for the assessment of the cardio-vascular risk. A
      commentary of the lipid profile for the clinician and mostly for the patient
      should be stated on the lab report. Quantifying the cardio-vascular risk using
      the SCORE (systematic coronary risk estimation) system, as recommended by the
      Haute autorite de sante (HAS), is the starting point to establish therapeutic
      goals and treatment strategies. It may be important to emphasize therapeutic
      goals in lipid reports in order to better monitor lipid profiles at appropriate
      intervals to assess compliance and therapeutic efficacy for patients on lipid
      lowering therapy.

PMID- 29072175
TI  - IQC Laboratory management strategy for medical biology.
AB  - Medical biology laboratories rely especially on internal quality control (IQC) to
      monitor the performance of equipment and ensure results reliability. Strategies
      for these controls vary considerably from one laboratory to another. Some
      laboratories use Westgard's rules to detect drifts and are faced with a large
      number of false rejections caused by frequent runs of control samples and
      strategies that activate all rejection rules, regardless of the analyte
      considered. To minimize these rejections, some laboratories have combined several
      theories, sometimes despite the relevance of the resulting strategy. In this
      article, we want to explain the foundations of the main IQC theories and set out
      a strategy to optimize the detection of problems while minimizing false IQC
      rejections. We will also address some frequently asked questions from
      laboratories as part of ISO 15189 accreditation.

PMID- 29072176
TI  - Premature Coronary Artery Disease due to Homozygous Familial Hypercholesterolemia
      in a 12-Year-Old Girl.
AB  - BACKGROUND: Homozygous familial hypercholesterolemia is a rare inherited
      metabolic disease caused by low-density lipoprotein receptor abnormality.
      Patients with homozygous familial hypercholesterolemia have an increased risk of
      cardiovascular complication that usually occurs in the first decade of life.
      Here, we report a 12-year-old girl with an unpredicted presentation for coronary
      artery disease and found to have homozygous familial hypercholesterolemia. CASE
      REPORT: A 12-year-old girl was admitted to our unit with syncope. Chest X-ray
      showed bilateral diffuse pneumonic consolidation and mild cardiomegaly. We
      detected stable ST depression by electrocardiography. Echocardiography showed
      normal systolic functions. Troponin-1 levels were high (66 mcg/dL, upper limit:
      0.04 mcg/dL). Influenza A virus DNA was detected by the respiratory viral panel.
      After her successful treatment for acute pneumonia and myocarditis due to
      Influenza A virus, her syncope attacks persisted. Marked ST elevation was
      observed during exercise electrocardiography. Coronary angiography showed severe
      occlusions in the coronary arteries. High serum levels of total cholesterol (756
      mg/dL) and low-density lipoprotein-C (556 mg/dL) were noticed. She had no tendon
      xanthomas. Medical histories revealed that her family members were diagnosed with
      heterozygous familial hypercholesterolemia. A coronary bypass surgery was
      performed. Statin and ezetimibe treatments were started. We also planned lipid
      apheresis. CONCLUSION: Children with homozygous familial hypercholesterolemia may
      present with symptoms of premature coronary heart disease requiring a routine
      lipid test and careful anamnesis.

PMID- 29072177
TI  - Effects of Intradermal Sterile Water Injections in Women with Low Back Pain in
      Labor: A Randomized, Controlled, Clinical Trial.
AB  - BACKGROUND: In addition to the pain caused byuterine contractions during labour,
      continuous and severe back pain is observed in 33% of women. Several
      pharmacological and nonpharmacological methods are available for managing this
      pain. Sterile water injection is considered as alternative method for
      nonpharmacological pain management. AIMS: To assess the satisfaction level and
      effectiveness of sterile water injection for back pain among women in labour.
      STUDY DESIGN: Randomized controlled trial. METHODS: A total of 168 term, healthy
      women with labour pain and severe back pain were randomized into the sterile
      water injection (study) and dry injection (placebo) groups. Injections were
      applied to the rhombus of Michaelis in the sacral area. Pain scores were assessed
      at 10, 30, 60, 120, and 180 min using a visual analogue scale. Additionally, the
      need for epidural analgesia, Apgar score, mode of delivery, time of delivery,
      maternal satisfaction, and breastfeeding score were assessed. RESULTS: The mean
      back pain scores at 30 min after injections were significantly lower in the study
      group (study group: 31.66+/-11.38; placebo: 75+/-18.26, p<0.01). The mean
      decrease in pain scores after 30 min according to baseline was significantly
      higher in the study group (study group: 54.82+/-7.81; placebo: 13.33+/-12.05,
      p<0.01). The need for epidural analgesia, time of delivery, mode of delivery, and
      Apgar and breastfeeding scores were similar in both groups. Maternal satisfaction
      from the analgesic effect was significantly higher in the study group (study
      group: 84.5%; placebo: 35.7%, p<0.01). CONCLUSION: The application of sterile
      water injection is effective for relieving back pain in the first stage of labour
      and has a sufficient satisfaction level among women.

PMID- 29072178
TI  - Relationships of nuclear, architectural and International Federation of
      Gynecology and Obstetrics grading systems in endometrial cancer.
AB  - OBJECTIVE: To examine correlations among nuclear, architectural, and
      International Federation of Gynecology and Obstetrics (FIGO) grading systems, and
      their relationships with lymph node (LN) involvement in endometrioid endometrial
      cancer. MATERIAL AND METHODS: Histopathology slides of 135 consecutive patients
      were reviewed with respect to tumor grade and LN metastasis. Notable nuclear
      atypia was defined as grade 3 nuclei. FIGO grade was established by raising the
      architectural grade (AG) by one grade when the tumor was composed of cells with
      nuclear grade (NG) 3. Correlations between the grading systems were analyzed
      using Spearman's rank correlation coefficients, and relationships of grading
      systems with LN involvement were assessed using logistic regression analysis.
      RESULTS: Correlation analysis revealed a significant and strongly positive
      relationship between FIGO and architectural grading systems (r=0.885, p=0.001);
      however, correlations of nuclear grading with the architectural (r=0.535,
      p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and
      statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN
      involvement rates differed significantly between tumors with AG 1 and those with
      AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast,
      although the difference in LN involvement rates failed to reach statistical
      significance between tumors with NG 1 and those with NG 2, it was significant
      between NG 2 and NG 3 (p=0.042). Although all three grading systems were
      associated with LN involvement in univariate analyses, an independent
      relationship could not be established after adjustment for other confounders in
      multivariate analysis. CONCLUSION: Nuclear grading is significantly correlated
      with neither architectural nor FIGO grading systems. The differences in LN
      involvement rates in the nuclear grading system reach significance only in the
      setting of tumor cells with NG 3; however, none of the grading systems was an
      independent predictor of LN involvement.

PMID- 29072179
TI  - Role of Chronobiology as a Transdisciplinary Field of Research: Its Applications
      in Treating Mood Disorders.
AB  - Chronobiology is a field that studies the effects of time on biological systems.
      Periodicity is of particular interest. The master biological clock in the
      suprachiasmatic nucleus controls daily rhythms of core body temperature, rest
      activity cycle, physiological and behavioral functions, psychomotor functions and
      mood in humans. The clock genes are involved in the generation of the circadian
      rhythms and the biological clock is synchronized to solar day by direct photic
      inputs. Various circadian rhythm abnormalities have been demonstrated in mood
      disorders such as unipolar depression, bipolar depression and seasonal affective
      disorder. Hypotheses involving circadian rhythm abnormalities related to the
      etiology of mood disorders have been raised. The resulting circadian rhythm
      changes can be measured and evaluated that these techniques can be used to
      identify subtypes of mood disorders associated with circadian rhythm changes. The
      data obtained from chronobiological studies reveal methods that manipulate
      circadian rhythms. The effects of light and melatonin on circadian rhythms are
      determined by these studies. Chronobiological research has been applied to the
      psychiatric clinic and light therapy has been used as a chronotherapeutic in the
      treatment of mood disorders. On the other hand, chronotherapeutic approaches with
      effects on circadian rhythms such as sleep deprivation therapy have been used in
      the treatment of mood disorders too. As a good example of translational
      psychiatry, chronobiological studies have been projected in the psychiatry
      clinic. It may be possible, the data obtained from the basic sciences are used in
      the diagnosis of mood disorders and in the treatment of psychiatric disorders as
      chronotherapeutic techniques. Developments in the field of chronobiology and data
      obtained from chronotherapeutics may enable the development of evidence-based
      diagnosis and treatment in psychiatry.

PMID- 29072180
TI  - Clinicopathologic and survival results in serous endometrium carcinoma and
      subgroup analysis for mixed serous and pure serous histology.
AB  - OBJECTIVE: To review the clinicopathologic and survival outcomes of patients with
      serous endometrial cancer (EC) and to investigate subgroup analysis based on pure
      serous and mixed serous EC subtypes. MATERIAL AND METHODS: Patients who underwent
      EC surgery between 2002 and 2014 and who were reported as serous EC were enrolled
      in the study. All patients were diagnosed as having serous EC or mixed serous EC
      with serous component higher than 10% based on the postoperative pathology
      report. RESULTS: A total of 93 patients were analyzed. The median disease-free
      and overall survival (OS) durations were 49.6 and 32.2 months, respectively.
      Forty-three patients (46.2%) relapsed and 35 patients (37.6%) died. The
      histologic type was pure serous EC in 52 (55.9%) and mixed EC in 41 (44.9%)
      patients. There was no statistical difference between the pure serous and mixed
      serous groups in terms of age, International Federation of Gynecology and
      Obstetrics stage, lymphadenectomy, lymph node metastasis or adjuvant therapy
      combinations. Twenty-nine (55.8%) patients in the pure serous group and 14
      (34.1%) in the mixed serous group hade recurrence (p=0.038). Twenty-five (48.1%)
      patients in the pure serous group and 10 (24.4%) in the mixed serous group died
      (p=0.034). In the pure serous group, the mean disease-free and OS durations were
      shorter than in the mixed serous group (59 vs. 81 months and 73 vs. 95 months,
      log-rank p=0.055 and 0.041, respectively). Histologic type was a significant
      prognostic factor on recurrence and OS in the univariate analysis (Hazard ratio:
      2.404, 95% Confidence interval: 1.01-5.71; 2.027, respectively), but not in the
      multivariate analysis, which included disease stage and age of the patients.
      CONCLUSION: Compared with pure serous and mixed serous endometrium cancer groups,
      primary surgical treatments, clinicopathologic features and adjuvant treatments
      were similar, but there was a survival difference. Patients with pure serous
      cancer had a worse prognosis. However histology was not an independent factor for
      survival.

PMID- 29072181
TI  - Primary Clear Cell Sarcoma of the Dermis Mimicking Malignant Melanoma.
AB  - BACKGROUND: Clear cell sarcoma is a rare malignant soft tissue neoplasm that
      typically involves tendons and aponeurosis. Clear cell sarcoma in the dermis is
      an extremely rare occurrence, and it is difficult to differentiate between this
      neoplasm and dermal malignant melanoma because they have similar morphologic and
      immunohistochemical features. Although rare, clear cell sarcoma of the skin
      typically occurs in the extremities. To our knowledge, there are no reported
      cases of primary clear cell sarcoma of the skin occurring in the neck. Here, we
      report an unusual case of clear cell sarcoma arising in the skin of the neck.
      CASE REPORT: A 43-year-old female presented with a right neck lesion. Histologic
      sections of the lesion showed a nodular proliferation of spindle cells with pale
      cytoplasm with epithelioid features involving the entire dermis with no epidermal
      component. The tumour cells were positive for melanocytic markers, including S100
      and Human Melanoma Black 45, which led to an initial diagnosis of malignant
      melanoma. Fluorescence in situ hybridization showed a rearrangement of the EWSR1
      gene on chromosome 22q12, which led to a diagnosis of primary clear cell sarcoma
      in the skin. CONCLUSION: Because the treatments for clear cell sarcoma and
      conventional melanoma are different, fluorescence in situ hybridization for EWSR1
      should be performed in any dermal lesions with melanocytic features that do not
      have an in situ component.

PMID- 29072182
TI  - Social challenges of contemporary psychiatry.
AB  - Psychiatry and society are interrelated and the biopsychosocial model continues
      to dominate the clinical psychiatric practice. Some doubts have been expressed in
      recent years about the value and the wide acceptance of the biopsychosocial
      model. Ghaemi (2009)1 considers it to be anti-humanistic and advocates the use of
      less eclectic, less generic, and less vague alternatives. The fundamental changes
      that have been witnessed in our times across the spectrum of biology, psychology
      and sociology have made necessary that a conceptual clarity should prevail. The
      remarkable advances in neurosciences, neurobiology and genetics tend to swing the
      emphasis towards a more biological basis. Psychosis for example is the condition
      often regarded as being biologically constructed and most independent of the
      social context. The symptoms, however, of hallucinations and delusions in
      psychosis have social meaning for the person experiencing them and are primarily
      defined socially.2 Furthermore, vulnerability is often the result of social
      trauma, whether in the form of recent stressors that trigger onset, or earlier
      circumstances that shape cognitive and emotional style. Moreover, the approved
      treatment and management of long term psychiatric disorders has involved
      interventions that are either directly social, or psychosocial. Furthermore,
      doubts have also been raised by the endophenotype project,3 related to the
      genetics of schizophrenia. Cohen4 suggested that there may be more individual
      genotypic patterns associated with schizophrenia than people with schizophrenia
      on the planet. A recent alternative interpretation (network approach) is gaining
      some support. It suggests that a stressor causes symptoms that activate other
      symptoms, in a circular, self-reinforcing way.5 This theory moves away from
      psychiatric disorders being traditionally conceptualised as categorical or
      dimensional models. While psychiatry has shifted its focus to a more biological
      approach, social factors still have an important role in crosscultural diagnosis,
      psychiatric disorders relating to social deprivation, rehabilitation and enabling
      social inclusion. The degree to which society is willing to accept people with
      mental health problems has an obvious impact on their quality of life. We live in
      a period of cataclysmic social changes with disastrous wars, increased poverty
      and growing income inequality. The consequences on mental health are phenomenal
      with epidemics of self-harm and suicidality, higher rates of depression, and
      intensifying diagnosis of mood and conduct disorders in children and young
      adults. Other adversities include the disproportional number of people with
      mental health problems in prisons and penal institutions, the massive escalation
      of dementia sufferers and the shortcomings of the aspirations of community mental
      health care. In addition, there is an escalating social pathology with
      significant numbers of refugees and asylum seekers and rising numbers of homeless
      particularly in urban areas of the developed world. We should not, however,
      overlook the better rates of treatment for mental health problems, the emphasis
      on human rights, the empowerment and the service users' participation and the
      development in global mental health. All these social factors are important to
      contemporary psychiatry presenting complex challenges and demanding urgent
      attention and action.6 There is a need to embrace the development of evidence
      based mental health services and a pluralistic approach, which balances
      appropriately the relevance of biological, psychological and social factors
      associated with mental health problems. The concept Meta-Community mental health
      builds on the successes of biological, psychological, social and community
      psychiatry.7 It incorporates neurosciences, sociology, psychology and
      anthropology and is delivered wherever the evidence shows that it makes a
      difference, whether in community or hospital, prisons, schools, court-room, place
      of work, refugee camp or battle-front. New technologies should be included for
      public information and education together with e-mental health, training of
      providers, tele-psychiatry and self-help methods delivered via IT. The boundaries
      of mental health are enlarging very rapidly and indeed new stakeholders and
      partners should be welcomed. This opens exciting possibilities but also creates
      some risks and strong evidence base should continue to guide us. Likelihood of
      finding early diagnostic and individualized treatment for psychosis, autism and
      dementia are likely to be of high financial cost. The importance of the social
      challenges of modern psychiatry was recognised by including mental health for the
      first time in the New Sustainable Development Goals of United Nations that will
      determine the global development by 2030 aiming at the promotion of life
      expectancy for all.8 Strengthening the prevention and treatment of mental health
      problems is a massive task for sustainable development as mental health has a
      direct impact on the whole range of Sustainable Development Goals.

PMID- 29072183
TI  - Assessing depression in Greek dementia patients: Which scale to use?
AB  - Depression in dementia is known to deteriorate patients' cognitive function and
      Quality of Life and to increase the burden of care. Although detecting depression
      in dementia is crucial, there is no gold standard for its screening and
      diagnosis. We examined the psychometric properties of 3 different scales in
      detecting depression in dementia. Results will be useful as community services
      for dementia in the country are developing and the need for reliable detection of
      depression in dementia patients is urgent. Our sample consisted of 136 Greek
      dementia patients who consulted a memory clinic. For the diagnosis of depression,
      DSM-IV criteria for major depression and 3 different depression measures were
      used: a self-assessment scale (Geriatric Depression Scale; GDS), a caregiver
      assessment scale (Neuropsychiatric Inventory-Depression; NPI-D) and a clinician
      rated scale (Cornell Scale for Depression in Dementia; CSDD). For the evaluation
      of the screening performance of the three depression scales receiver operating
      characteristic curve (ROC) analysis was applied. The DSMIV criteria served as the
      gold standard method for the diagnosis of major depression. CSDD showed the best
      psychometric properties for the diagnosis of depression in dementia. The ROC
      curve analysis revealed that among the three measures, the CSDD had the wider AUC
      (0.919), second in the width of the AUC was the GDS (0.871), and last was the NPI
      D (0.812). The prevalence of depression ranged from 18.4% according to DSM-IV
      criteria to 42.6% using the NPI-D. Using the GDS (cut off point: 7/8) and the
      CSDD (cut off point: 6/7), depression was present in 26.9% and 33.1% of the
      patients, respectively. Correlations between scales used were significant (r from
      0.432 to 0.660; p<0.001). Caregivers tend to report more depressive symptoms in
      dementia compared to patients' and clinicians' ratings. CSDD should be used in
      specialized centers, but GDS may be an alternative in patients able to complete
      the assessment. The need to establish valid criteria for the diagnosis of
      depression in dementia is urgent.

PMID- 29072184
TI  - Dysfunctional internet behaviour symptoms in association with personality traits.
AB  - Internet addiction is a matter of great interest for researchers, taking into
      consideration Internet's rapid spread and its ever growing use in children,
      adolescents and adults. It has been associated with multiple psychological
      symptoms and social difficulties, therefore raising even greater concerns for its
      adverse consequences. The present study that consists part of a broader research,
      aims to investigate the association between excessive Internet use and
      personality traits in an adult population. Specifically, the research examined
      the relation between dysfunctional internet behaviour and personality traits as
      neuroticism and extraversion, the two personality dimensions that have arisen as
      the most important ones in all relevant research. Our main hypotheses are that
      dysfunctional internet behaviour would be positively associated with neuroticism
      but negatively linked to extraversion. The 1211 participants aged over 18 years,
      completed the IAT (Internet Addiction Test) by Kimberly Young and the Eysenck
      Personality Questionnaire (EPQ) and some other questionnaires detecting
      psychopathology. Additionally, part of the administered questionnaires concerned
      socio-demographic characteristics of the participant subjects: specifically sex,
      age, marital status, education (educational years), place of residence -urban,
      semi-urban and rural-, whether they suffer from somatic or mental health disorder
      and if they take medication for any of the above categories. All the
      questionnaires have been electronically completed by each participant. Results
      showed that 7.7% showed dysfunctional internet behaviour that concerns both
      medium and severe degree of dependence by the use of Internet, as measured by the
      use of IAT. The univariate logistic regression analysis revealed that the
      individuals exhibiting symptoms of dysfunctional internet behaviour were more
      likely to suffer from a chronic mental health disorder, to use psychotropic
      medication and to score higher on neuroticism. In contrast, they were less likely
      to have children and be extraverted. Multiple logistic regression analysis
      confirmed that neuroticism and extraversion were independently associated with
      dysfunctional internet behaviour. Individuals with high scores on neuroticism
      were more likely to meet the criteria for dysfunctional internet behaviour, while
      high scores on extraversion were associated with a lower probability of
      dysfunctional internet behaviour. Identification of personality traits that could
      be connected to some sort of "addictive personality" -particularly neuroticism
      and Introversion- might help researchers to identify and prevent internet
      addiction on the early stages and possibly could have a positive contribution to
      the therapeutic treatment of this addiction disorder.

PMID- 29072185
TI  - Translation and validation of the greek Psoriatic Arthritis Quality of Life
      Scale.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory disease that has a
      significant impact on patients' quality of life (QoL). The Psoriatic Arthritis
      Quality of Life (PsAQoL) Scale was developed in the UK to be specific to PsA
      patients and adopts the needs-based model of QoL. As a disease-specific measure,
      the PsAQoL is superior to generic measures of QoL in terms of relevance and
      sensitivity. The measure, which has been adapted into 50 languages, has not
      previously been available for use with Greek PsA patients. The aim of the study
      was to produce a Greek version of the PsAQoL that was suitable for native Greek
      speakers and that had comparable psychometric properties to the original UK
      version. The adaptation of the Greek PsAQoL consisted of three stages;
      translation, assessment of face and content validity and analysis of its
      psychometric properties. The translation stage adopted the dual panel methodology
      -a bilingual panel followed by a lay panel- to ensure conceptual equivalence of
      the scale to the original version. Cognitive debriefing interviews were conducted
      to determine the applicability and relevance of the adapted scale to patients.
      Finally, a postal validation survey was conducted to assess the psychometric
      properties of the draft measure, using the Nottingham Health Profile (NHP) as a
      comparator instrument. Non-parametric statistical analyses were performed to
      establish the reliability and construct validity of the PsAQoL. The translation
      panels produced a language version that sounded natural to native Greek speakers.
      Interviews revealed that patients found the measure comprehensible and
      appropriate. Only minor grammatical changes were made to the measure following
      these interviews. The Greek PsAQoL demonstrated good internal consistency
      (Cronbach's alpha=0.88) and excellent test-retest reliability (r=0.98). As
      expected, the measure correlated moderately highly with the Physical Mobility and
      Pain sections of the NHP and correlated moderately with other sections,
      indicating convergent validity. Known group validity was established by the
      ability of the measure to distinguish between patients who differed according to
      their perceived general health and disease severity. No significant differences
      in PsAQoL scores were observed between males and females or older and younger
      patients. The Greek PsAQoL was well-received by patients and demonstrated sound
      psychometric properties. It forms part of a growing body of disease-specific
      measures that are available in Greece. It is recommended for use in routine
      clinical practice, international clinical trials and research studies as a valid
      and reliable measure of QoL in PsA patients.

PMID- 29072186
TI  - Greek teachers' knowledge about attention deficit hyperactivity disorder.
AB  - Attention deficit hyperactivity disorder (ADHD) is a neurobiological disorder,
      which affects about 5.2% of school-aged children worldwide. Children with ADHD
      present teachers with a special challenge, since they interfere with teaching
      process and do not respond to typical classroom management techniques. In order
      to meet this challenge teachers must have accurate, up-to-date, information about
      the disorder so that they can respond to the needs of the student with ADHD.
      Studies that have examined teachers' beliefs and knowledge relating to ADHD
      highlighted the need for providing training to increase Greek teachers' knowledge
      and understanding of the disorder. Thus, the aims of the present study were: (a)
      to develop and evaluate brief ADHD training seminar for teachers; and (b) to
      investigate whether the training format (half-day versus two-day seminar) would
      have a differential effect on teachers' knowledge about ADHD. A total of 143
      teachers formed the two sample groups; Group 1 (n=68) attended a half-day
      training (5 hours), and Group 2 (n=75) a two-day training (18 hours). Seminar
      topics included: (a) gaining basic knowledge about the symptoms, causes and
      natural history of ADHD, (b) understanding the key underlying cognitive deficits
      of the disorder and their impact on learning and behavior, (c) implementation of
      specific learning strategies for children with ADHD, (d) benefits and limitations
      of existing treatment approaches including the pharmacological treatment, and (e)
      available instruments for teachers that could inform their decision to refer the
      student to CAMHS for an assessment. A self-report ADHD Knowledge Questionnaire
      (ADHD-KQ), which covers four domains (clinical presentation, causes, cognitive
      deficits, interventions) was developed for the purpose of the present study, and
      was administered pre- and post-seminar. Teachers were generally knowledgeable
      about clinical presentation of ADHD, with more than 80% of the sample responding
      correctly to items pertaining to core symptoms. The internal consistency of the
      total ADHD-KQ scale measured by Cronbach's alpha coefficient was found to be good
      (0.89). The alpha coefficients for the sub-scales were acceptable (0.70 for the
      Symptoms/Diagnosis sub-scale, 0.73 for the Cognitive Deficits sub-scale, and 0.75
      for the Intervention sub-scale), except for the Causes sub-scale, which was poor
      (0.59). In addition, each of the sub-scales showed a significant correlation with
      the total scales score (range r=0.66 to r=0.79), and there also was significant
      correlation between the four sub-scales (range r=0.39 to r=0.45). As expected,
      gaps in knowledge were identified, particularly in the area of causes,
      pharmacological treatment and cognitive deficits associated with ADHD. The
      results, using paired samples t tests, showed a highly significant increase in
      ADHD-KQ total and all sub-scale scores in both groups (p<0.001), indicating an
      overall improved knowledge about ADHD irrespective of the training format, i.e.
      half-day versus two-day training seminar. One-way MANOVA revealed significant
      difference between the two training seminars in mean pre-post difference sub
      scale scores considered simultaneously. Subsequent univariate tests of between
      subjects effects revealed that the group (training format) had a statistically
      significant effect on ADHD knowledge of symptoms sub-scale only [F(1,141)=10.46,
      p<0.01], with those who participated in the two-day training seminar having
      significantly higher mean pre-post difference scores as compared to teachers who
      attended the half-day training seminar (p<0.01). The present findings merit
      replication and, if confirmed in larger samples, have important implications for
      undergraduate curriculum development and training of practicing teachers, so that
      to overcome specific knowledge gaps and misconceptions with regards to ADHD.
      Future study should incorporate the use of classroom interventions and teaching
      strategies for students with ADHD, before and after brief training seminar, for a
      more thorough evaluation of its effectiveness.

PMID- 29072187
TI  - Substance abuse and cancer.
AB  - Substance abuse is a health problem with serious psychological and psychiatric
      dimensions and multiple social and economic consequences. Cancer is a disease
      that threatens not only life and physical integrity but mental health as well.
      Oncology patients suffer from mental disorders in high rates, especially from
      depression and anxiety. The role of substance abuse in the pathogenesis of cancer
      is studied systematically, since there are research data supporting the mutagenic
      effects of certain substances. It has been supported that a possible
      dysregulation of the immune system is linked to the oncogenic processes induced
      by substances of abuse. Specifically, opioids are the first addictive substances
      that have been identified as oncogenic factors. However, conflicting results have
      been offered by experimental animal studies, which showed that opioids, such as
      morphine, depending on the dosage administered, may not only enhance the process
      of tumor growth, but also inhibit it. Additionally, research data indicate that
      the use of cannabis may be associated with cancer, either as an independent
      factor or in relation to other mutagenics, although it is not yet clear to which
      extent these effects may be connected to the disease, especially once the
      consumption of tobacco and alcohol by these patients are taken into account.
      However, it has been argued that certain cannabinoids may have biological 
      anticancer- activities which could be used therapeutically without being
      accompanied by the corresponding 9-tetrahydrocannabinol psychoactive effects. It
      is well known that alcohol is a risk factor for developing head and neck cancer,
      and epidemiological studies indicate that the higher the consumption of alcohol,
      the more mortality due to cancer increases. In addition, it is suggested that
      there is no safety level for alcohol consumption regarding the risk of developing
      cancer; that is even a minimum daily consumption is associated with the
      occurrence of certain types of cancer. Specific components have been identified
      in tobacco, which are considered to be carcinogenic and responsible for tumor
      development in various sites. Moreover, complicated psychiatric problems arise
      due to substance abuse in cancer patients, either in the context of pain
      treatment, or under pre-existing dependence. The rational use of opioid
      analgesics, when it is medically required as suggested by the health
      professionals specialized in the treatment of acute pain in cancer patients,
      could be a therapeutic option. Substance abuse reduces treatment compliance,
      worsens cancer prognosis and seems to be a negative factor for the quality of
      life of these patients. Current literature highlights the importance of
      appropriate psychiatric interventions to address substance abuse in cancer
      patients.

PMID- 29072188
TI  - Body dysmorphic disorder: Latest neuroanatomical and neuropsychological findings.
AB  - Body dysmorphic disorder (BDD) is characterized by a preoccupation with a
      perceived defect or flaw in physical appearance that is not observable or appears
      slight to others. It leads to severe distress and functional impairment.
      Cognitive-behavioural and neurobiological similarities to obsessive compulsive
      disorder (OCD) have led to its newly conceived classification as an obsessive
      compulsive related disorder (OCRD). In the process of investigating the
      neurobiology of BDD, neuroimaging and neuropsychological studies have been
      conducted. This review presents the most recent research findings and their
      connection with BDD clinical features. Imaging studies have shown increased total
      white matter volume and caudate volume asymmetry in BDD patients. These findings
      are consistent with the striatal topography model of OCRDs. Other studies have
      showed perfusion deficits in bilateral anterior-medial temporal and occipital
      regions and asymmetric perfusion in parietal lobes. In addition, correlation
      between symptom severity and left inferior frontal gyrus volume reflects the
      degree of detailed, analytic encoding that occurs on day-to-day basis when
      viewing others and themselves, and that likely underlies their symptoms. Finally,
      positive correlation between right amygdala volume and symptom severity signifies
      pathological fear circuitry engagement, hypervigilance and heightened sensitivity
      to social situations. Neuropsychological studies of BDD reveal deficits in
      strategic organization, learning and free recall after short and long delays.
      Executive function deficits are related to spatial working memory and subsequent
      thinking speed as well as impaired higher level planning ability. BDD patients'
      organizational strategies tend to focus on detail rather than on larger, global
      clustering features. They are characterized by abnormal visual processing of both
      details and global elements, inaccurate processing of global elements and reduced
      flexibility in switching visual attention between global and local features.
      Moreover, BDD patients seem to have deficits in identifying facial emotional
      expressions and they tend to misinterpret expressions of disgust (and others) as
      anger. Poor insight and ideas of reference, common in BDD, might be related to
      emotion recognition biases for angry expressions. These findings have been
      supplemented by combined neuroimaging and neuropsychological studies. Left
      hemisphere hyperactivity for low and normal spatial frequency face tasks and
      abnormal activation of the amygdala for high and low spatial frequency face tasks
      suggests detail encoding and analysis in BDD. Patients may primarily perceive
      details but they are impaired in their ability to contextualize them
      holistically.

PMID- 29072189
TI  - Association of maternal depression with children's attention deficit
      hyperactivity disorder.
AB  - Family problems are considered to be the main risk factor leading to the
      development of behavi oural problems during childhood and adolescence as well. A
      well documented fact in the current literature is that psychopathology of any
      kind in parents may influence behaviour, personality and appearance of
      psychopathology in their children. The permanent interaction between children's
      psychopathology or any kind of developmental disorder on one hand and parental
      psychopathology on the other, is considered to be one of the most important
      fields of research during the last decades. The aim of the present study was to
      review research concerning the relationship between maternal depressive disorder
      and children's attention deficit hyperactivity disorder (ADHD) among members of
      the same family, the influence that each disorder has in the appearance and
      development of the other, and the way that the mother-child relationship is
      influenced by both. We conducted an electronic search through PubMed to detect
      articles concerning the association of maternal depressive disorder and
      children's ADHD among the members of the same family published in English from
      January 1980 to December 2015. The choice was strictly limited to articles
      concerning exclusively emotional disorders in mothers and ADHD in their children.
      This process concluded with the electronic research of bibliographic citations of
      the identified articles, or related articles, in order to locate additional
      sources. Considering as a fact the interaction between this developmental
      disorder, ADHD, and mother's psychological profile which is maternal depression
      for the present research, we report the following: among the 27 articles found,
      24 concerned the influence of the mother's depression to the child's ADHD, and
      the remaining 3 concerned their genetic association. There were important
      limitations found as well. Despite the fact that all the studies included a
      control group, many of them did have a follow-up and were short-term studies.
      Their results were mostly heterogenous and therefore their meta-analysis proved
      impossible. There was evidence concerning the association between the two
      disorders as both maternal depressive disorder and children's ADHD influence each
      other through multiple psychosocial and biological factors. Nevertheless, more
      data is needed from well structured, homogenous studies, especially in the field
      of genetics, in order to document this association.

PMID- 29072190
TI  - Employment insecurity, mental health and suicide.
AB  - With the economic crisis an increase in suicidality has been reported across
      Europe but especially in Greece. Tauhese reports hit the mass media headlines and
      were also included in the debate among political parties. The literature suggests
      that during periods of deep economic crisis, there is an increase specifically in
      suicides but causality remains unclear. The prevailing picture both in the
      scientific literature and in the mass media is that the economic crisis acts as a
      more or less generic risk factor on the entire population putting at risk
      literally anybody. Two recent studies clearly dispute it by reporting that
      suicides had increased several months before unemployment increased. Additionally
      and specifically concerning Greece, where the economic crisis is deeper and more
      prolonged, the detailed inspection of age and gender specific rates are not in
      accord with a "male gender" by "unemployment" interaction. Taking into
      consideration the above and since the rise in suicides also affects prospering
      countries without high unemployment, including Germany and Norway, another
      possible explanation is that the changes in the socioeconomic environment and
      especially in the employment conditions have overstressed vulnerable populations
      (e.g. mental patients) leading to the increased suicide rates. The problem is
      that in the majority of the literature the economic crisis/austerity is
      considered to be a generic risk factor affecting the entire population and
      subsequently generic horizontal measures are proposed. Unfortunately patients at
      risk to commit suicide are not considered as such; instead they are rather
      considered as normal healthy people from the general population who respond with
      suicide to generic adverse events.

PMID- 29072191
TI  - Compulsory admissions in southwest Greece 2010-2011: A descriptive report.
AB  - Compulsory admissions represent a significant proportion of psychiatric
      hospitalizations. A wide variation seems to exist internationally regarding legal
      frameworks, administrative procedures, detention rates and clinical practice. The
      aim of the present study is to describe qualitative and quantitative features of
      compulsory admissions in a large administrative area in southwest Greece, in
      order to identify targets for future research and possible remediation.
      Involuntary assessments and admissions in the Department of Psychiatry of the
      University Hospital of Patras were retrospectively assessed, during a 12-month
      period, for demographic features and data regarding legal procedures. Diagnoses
      following compulsory first assessment and at discharge were recorded for the
      patients who were admitted in our department. During the period of observation,
      218 compulsory assessments were made, corresponding to 190 patients and resulting
      in 183 compulsory admissions. Thirty five cases (16.1%) were assessed as not
      justifying hospitalization and corresponded mainly to the diagnoses of alcohol
      and/or substance abuse or dependence. Involuntary hospitalizations represented
      44.9% of all psychiatric admissions in our department. Diagnosis at first
      assessment was most frequently psychosis (68.4%). Diagnoses at discharge were
      most often schizophrenia (52.8%) and bipolar disorder (21.3%). A history of
      multiple hospitalizations (>5) was observed in 17 (15.8%) patients, whereas 46
      patients (42.6%) were hospitalized for the first time, and 13 (11.7%) exhibited
      their first psychotic episode. Of the 108 patients who were admitted in our
      department, 88 (81.5%) declared that they did not wish to attend the court
      hearing, 7 (6.5%) were not able to attend due to severe health condition, and
      only 13 (12.0%) actually presented in court. Concluding, current situation
      regarding legal procedures, involuntary admissions and mental health care in
      Greece is rather far from satisfying. Future directions should include the
      systematic recording of mental health care parameters, such as compulsory
      hospitalizations, as well as efforts to improve these parameters and the existing
      legal framework and procedures.

PMID- 29072192
TI  - K-edge energy-based calibration method for photon counting detectors.
AB  - In recent years, potential applications of energy-resolved photon counting
      detectors (PCDs) in the x-ray medical imaging field have been actively
      investigated. Unlike conventional x-ray energy integration detectors, PCDs count
      the number of incident x-ray photons within certain energy windows. For PCDs, the
      interactions between x-ray photons and photoconductor generate electronic voltage
      pulse signals. The pulse height of each signal is proportional to the energy of
      the incident photons. By comparing the pulse height with the preset energy
      threshold values, x-ray photons with specific energies are recorded and sorted
      into different energy bins. To quantitatively understand the meaning of the
      energy threshold values, and thus to assign an absolute energy value to each
      energy bin, energy calibration is needed to establish the quantitative
      relationship between the threshold values and the corresponding effective photon
      energies. In practice, the energy calibration is not always easy, due to the lack
      of well-calibrated energy references for the working energy range of the PCDs. In
      this paper, a new method was developed to use the precise knowledge of the
      characteristic K-edge energy of materials to perform energy calibration. The
      proposed method was demonstrated using experimental data acquired from three K
      edge materials (viz., iodine, gadolinium, and gold) on two different PCDs (Hydra
      and Flite, XCounter, Sweden). Finally, the proposed energy calibration method was
      further validated using a radioactive isotope (Am-241) with a known decay energy
      spectrum.

PMID- 29072193
TI  - Development of poly (1,8 octanediol-co-citrate) and poly (acrylic acid)
      nanofibrous scaffolds for wound healing applications.
AB  - Wound care is one of the leading health care problems in the United States
      costing billions of dollars yearly. Annually, millions of acute wounds occur due
      to surgical procedures or traumas such as burns and abrasions, and these wounds
      can become non-healing due to bacterial infection or underlying pathologies.
      Current wound care treatments include the use of bioinert constructs combined
      with topical administration of anti-bacterial agents and growth factors. However,
      there is a growing need for the development of bioactive wound dressing materials
      that are able to promote wound healing and the regeneration of healthy tissue. In
      this work, we evaluate and report the use of a novel electrospun polymeric
      scaffold consisting of poly (1,8 octanediol-co-citrate) and poly (acrylic acid)
      for wound healing applications. The scaffold exhibits intrinsic antibacterial
      activity, hydrogel-like water uptake abilities, and the ability to deliver
      physiologically relevant concentrations of growth factor. Additionally, the
      scaffold shows antibacterial function when tested with bacteria relevant to wound
      healing applications. Biological characterization of the electrospun scaffold
      shows excellent cellular adhesion, low cytotoxicity, and enhanced proliferation
      of skin fibroblasts. This work has potential towards the development of novel
      bioactive scaffolds for prevention of bacterial infiltration into the wound bed
      and enhanced healing.

PMID- 29072195
TI  - Evaluation of water-mimicking solid phantom materials for use in HDR and LDR
      brachytherapy dosimetry.
AB  - In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose
      profiles generated in water or a water-equivalent phantom have to be available in
      the interest of patient safety. However, the commercially available brachytherapy
      photon sources cover a wide range of photon emission spectra, and the range of
      the in-phantom photon spectrum is further widened by Compton scattering, so that
      the achievement of water-mimicking properties of such phantoms involves high
      requirements on their atomic composition. In order to classify the degree of
      water equivalence of the numerous commercially available solid water-mimicking
      phantom materials and the energy ranges of their applicability, the radial
      profiles of the absorbed dose to water, D w, have been calculated using Monte
      Carlo simulations in these materials and in water phantoms of the same
      dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co
      60 HDR (60Co), Eckert und Ziegler BEBIG GmbH CSM-11 (137Cs), Implant Sciences
      Corporation HDR Yb-169 Source 4140 (169Yb) as well as the LDR therapy sources
      IsoRay Inc. Proxcelan CS-1 (131Cs), IsoAid Advantage I-125 IAI-125A (125I), and
      IsoAid Advantage Pd-103 IAPd-103A (103Pd). Thereby our previous comparison
      between phantom materials and water surrounding a Varian GammaMed Plus HDR
      therapy 192Ir source (Schoenfeld et al 2015) has been complemented. Simulations
      were performed in cylindrical phantoms consisting of either water or the
      materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT,
      Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue
      Water, polyethylene, polystyrene and PMMA. While for 192Ir, 137Cs and 60Co most
      phantom materials can be regarded as water equivalent, for 169Yb the materials
      Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the
      low-energy sources 106Pd, 131Cs and 125I, only Plastic Water LR can be classified
      as water equivalent.

PMID- 29072194
TI  - Cu-releasing bioactive glass/polycaprolactone coating on Mg with antibacterial
      and anticorrosive properties for bone tissue engineering.
AB  - Bioactive glass nanoparticles containing copper (Cu-BGNs) were introduced into
      polycaprolactone (PCL) coating systems to improve the bioactivity, antibacterial
      properties, and corrosion resistance of vulnerable magnesium matrices under
      physiological conditions. The influence of different amounts of Cu-BGNs in PCL
      coatings was thoroughly investigated in determining the wettability,
      electrochemical properties, and antibacterial effects against Staphylococcus
      carnosus and Escherichia coli, as well as their cyto-compatibility. Cu-BGNs were
      observed randomly scattered in PCL coatings. Increasing the concentration of Cu
      BGNs resulted in a slight decrease of the water contact angle, and a reduction in
      anticorrosion properties of the Cu-BGN composite coatings. Yet higher Cu-BGN
      content in coatings led to more calcium phosphate formation on the surface after
      7 days of immersion in Dulbecco's modified Eagle's medium, which was confirmed by
      Fourier-transform infrared spectroscopy and x-ray photoelectron spectroscopy. The
      growth of S. carnosus and E. coli was inhibited by Cu2+ ions released from the Cu
      BGN coatings. In addition, both direct and indirect cyto-compatibility
      experiments showed that the viability and proliferation of MG-63 cells on Cu-BGN
      coatings were highly increased compared to pure magnesium; however, an additional
      increase of Cu-BGN concentration showed a slight decrease of cell proliferation
      and cell activity. In summary, Cu-BGN/PCL composite coatings impart magnesium
      based biomaterials with antibacterial and anticorrosive properties for clinical
      applications.

PMID- 29072196
TI  - {?bb Z}-module defects in crystals.
AB  - An analysis is presented of the new types of defects that can appear in
      crystalline structures where the positions of the atoms and the unit cell belong
      to the same {?bb Z}-module, i.e. are irrational projections of an N > 3
      dimensional (N-D) lattice Lambda as in the case of quasicrystals. Beyond coherent
      irrationally oriented twins already discussed in a previous paper [Quiquandon et
      al. (2016). Acta Cryst. A72, 55-61], new two-dimensional translational defects
      are expected, the translation vectors of which, being projections of nodes of
      Lambda, have irrational coordinates with respect to the unit-cell reference
      frame. Partial dislocations, called here module dislocations, are the linear
      defects bounding these translation faults. A specific case arises when the
      Burgers vector B is the projection of a non-zero vector of Lambda that is
      perpendicular to the physical space. This new kind of dislocation is called a
      scalar dislocation since, because its Burgers vector in physical space is zero,
      it generates no displacement field and has no interaction with external stress
      fields and other dislocations.

PMID- 29072197
TI  - The phase problem for two-dimensional crystals. I. Theory.
AB  - Properties of the phase problem for two-dimensional crystals are examined. This
      problem is relevant to protein structure determination using diffraction from two
      dimensional crystals that has been proposed using new X-ray free-electron laser
      sources. The problem is shown to be better determined than for conventional three
      dimensional crystallography, but there are still a large number of solutions in
      the absence of additional a priori information. Molecular envelope information
      reduces the size of the solution set, and for an envelope that deviates
      sufficiently from the unit cell a unique solution is possible. The effects of
      various molecular surface features and incomplete data on uniqueness and
      prospects for ab initio phasing are assessed. Simulations of phase retrieval for
      two-dimensional crystal data are described in the second paper in this series.

PMID- 29072198
TI  - Extrinsic faulting in 3C close-packed crystal structures: computational mechanics
      analysis.
AB  - Extrinsic faulting has been discussed previously within the so-called difference
      method and random walk calculation. In this contribution it is revisited under
      the framework of computational mechanics, which allows expressions to be derived
      for the statistical complexity, entropy density and excess entropy as a function
      of faulting probability. The approach allows one to compare the disordering
      process of an extrinsic fault with other faulting types. The E-machine
      description of the faulting mechanics is presented. Several useful analytical
      expressions such as probability of consecutive symbols in the Hagg coding are
      presented, as well as hexagonality. The analytical expression for the pairwise
      correlation function of the layers is derived and compared with results
      previously reported. The effect of faulting on the interference function is
      discussed in relation to the diffraction pattern.

PMID- 29072199
TI  - About difference electron densities and their properties.
AB  - Difference electron densities do not play a central role in modern phase
      refinement approaches, essentially because of the explosive success of the EDM
      (electron-density modification) techniques, mainly based on observed electron
      density syntheses. Difference densities however have been recently rediscovered
      in connection with the VLD (Vive la Difference) approach, because they are a
      strong support for strengthening EDM approaches and for ab initio crystal
      structure solution. In this paper the properties of the most documented
      difference electron densities, here denoted as F - Fp, mF - Fp and mF - DFp
      syntheses, are studied. In addition, a fourth new difference synthesis, here
      denoted as {?overline F_q} synthesis, is proposed. It comes from the study of the
      same joint probability distribution function from which the VLD approach arose.
      The properties of the {?overline F_q} syntheses are studied and compared with
      those of the other three syntheses. The results suggest that the {?overline F_q}
      difference may be a useful tool for making modern phase refinement procedures
      more efficient.

PMID- 29072200
TI  - A note on X-ray spherical wavefields in the Laue case for perfect crystals.
AB  - Spherical wavefields in the Laue case are obtained when the real part of the
      crystal structure factor is zero or small compared with the imaginary part. The
      results are the same as in the conventional case where the real part is large.
      Through this work, it is shown that virtual wavefields on the vacuum side should
      be taken into account to explain the obtained results. It is also shown that, to
      obtain the virtual wavefields, a modification of the conventional spherical wave
      theory is necessary.

PMID- 29072201
TI  - The Rome de Lisle problem.
AB  - The 'Rome de Lisle problem' on the vertex and edge truncations has been
      formulated and solved for all crystal closed simple forms (two, eight, five and
      15 for orthorhombic, trigonal + hexagonal, tetragonal and cubic syngonies,
      respectively). The collections of simple forms obtained are enumerated and
      considered as special combinations of simple forms in symmetry classes.

PMID- 29072204
TI  - Why a radical overhaul of dentistry is needed.

PMID- 29072205
TI  - Burden of oral diseases in 2016: Newer opportunities for further research.

PMID- 29072206
TI  - Correlation of ultrasonographic measurements, histopathological grading, and
      clinical staging in oral submucous fibrosis.
AB  - AIMS AND OBJECTIVES: To evaluate the presence and thickness of submucosal
      fibrosis in oral submucous fibrosis (OSMF) patients ultrasonographically and to
      correlate these findings with the clinical stage and histological grade of OSMF.
      MATERIALS AND METHODS: Forty participants (twenty cases and twenty controls) were
      included in the study. The patients diagnosed clinically as having OSMF and
      consented for biopsy were included in the cases, and completely healthy
      individuals with no habit history or oral lesions were included in the control
      group after matching the body mass index. After clinically staging, the patients'
      transcutaneous ultrasonography (USG) was performed and after that punch biopsy
      was taken and the specimen was graded histopathologically. RESULTS: The data were
      statistically analyzed using Mann-Whitney test and Spearman's rank correlation.
      The cases showed increased submucosal thickness as compared to the controls. The
      USG measurements statistically correlated with the clinical stage and
      histopathological grade of OSMF. CONCLUSION: USG proves to be a valuable
      adjunctive modality in diagnosing, staging and also evaluating the prognosis of
      OSMF.

PMID- 29072207
TI  - Evaluation of sexual dimorphism using permanent maxillary first molar in Sri
      Ganganagar population.
AB  - AIM OF STUDY: The aim is to evaluate existence of sexual dimorphism by variation
      in right and left permanent maxillary molars using buccolingual width (BLW) and
      mesio-distal width (MDW) measured intraorally and on study casts among Sri
      Ganganagar population. MATERIALS AND METHODS: Fifty patients (25 males and 25
      females) with 17-25 years of age were selected. Impressions of maxillary arch
      were taken and the BLW and MDW were measured using digital Vernier calipers on
      study casts and intraorally. RESULTS: Highly significant correlation was found
      between MDW and BLW of both the maxillary permanent first molars for both genders
      (P < 0.05) intraorally. The MDW and BLW on study cast of both sides in both
      gender were more on left side in males while on right side in females.
      CONCLUSION: Left maxillary permanent first molar showed minimum mean difference
      of measurements on study cast and introrally than right, thus better predictor
      for gender dimorphism in forensics.

PMID- 29072208
TI  - Assessment of caries status among schoolchildren according to decayed-missing
      filled teeth/decayed-extract-filled teeth index, International Caries Detection
      and Assessment System, and Caries Assessment Spectrum and Treatment criteria.
AB  - BACKGROUND: Detection and evaluation of dental caries is of epidemiological
      importance. Its early detection is important to commence appropriate treatment
      planning. Cavitated, noncavitated, and initial lesions of dental caries can be
      detected by various indices. OBJECTIVES: The objective of the study was to assess
      the caries experience in schoolchildren using decayed-missing-filled teeth
      (DMFT)/decayed-extracted-filled teeth (deft), International Caries Detection and
      Assessment System-II (ICDAS-II), and Caries Assessment Spectrum and Treatment
      (CAST) systems. MATERIALS AND METHODS: An epidemiological survey was carried out
      among 1550 schoolchildren (37,644 teeth) between the age ranges of 4 and 14
      years. American Dental Association type III examination was performed using plane
      mouth mirrors and community periodontal index probes using DMFT/deft, ICDAS II,
      and CAST indices. RESULTS: Out of 37,644 teeth examined, 2,718 teeth had shown
      caries. Caries experience with DMFT/deft index was 5.54%. Highest score of DMFT
      was observed in deciduous dentition period (59.02%). Overall prevalence of dental
      caries with ICDAS and CAST system was 6.7% and 6.95%, respectively. The highest
      percentage of noncavitated lesions (ICDAS - 2.26% and CAST - 3.9%) and greater
      prevalence of caries among deciduous teeth (ICDAS - 53.2% and CAST - 58.7%) was
      observed with both ICDAS and CAST systems. CONCLUSION: A high prevalence of
      noncavitated lesions and less number of sealants and restorations indicates the
      lack of awareness for prevention and treatment of oral diseases, which suggests a
      strong need for preventive and operative treatments.

PMID- 29072209
TI  - Efficacy of botulinum toxin in treating myofascial pain and occlusal force
      characteristics of masticatory muscles in bruxism.
AB  - AIM AND OBJECTIVE: The present study was conducted in patients with bruxism to
      evaluate the effect of botulinum toxin type A (BTX-A) (Botox, Allergan, Inc.,
      Irvine, CA, USA) in the treatment of myofascial pain and the occlusal force
      characteristics of masticatory muscles. MATERIALS AND METHODS: Twenty-four
      diagnosed with bruxism were randomly divided into three groups (n = 8) and
      treated by bilateral intramuscular injection of BTX-A and placebo-treated with
      saline placebo injections and control group where no injections were given. The
      clinical parameters such as pain at rest and during chewing were assessed and
      occlusal force analysis system to measure the distribution of occlusal force in
      bruxism patients. All the three groups were assessed at baseline time and at 1
      week, 3 months, and 6 months follow-up appointments. Descriptive analysis showed
      that improvements in parameters such as pain at rest; pain during chewing
      clinical outcome variables were higher in the botox treated group than in the
      placebo-treated subjects. RESULTS: The pain at rest and at chewing decreased in
      the BTX-A group while remaining constant in the placebo group and control group.
      There was a significant change in maximum occlusal force in the BTX-A group
      compared with the other two groups (P < 0.05, post hoc Bonferroni test, no exact
      P value), and there was no significant difference between the placebo and control
      groups (post hoc Bonferroni test, no exact P value). CONCLUSION: Results from the
      present study supported the efficacy of BTX-A to reduce myofascial pain symptoms
      in bruxers, and effective in reducing the occlusal force.

PMID- 29072210
TI  - Evaluation of effect of laser etching on shear bond strength between
      maxillofacial silicone and acrylic resin subjected to accelerated aging process.
AB  - OBJECTIVE: Maxillofacial prosthesis are supported by implants, require a
      retentive matrix to retain the suprastructure. The retentive matrix is made up of
      acrylic resin to which the silicone prostheses are anchored by micro-mechanical
      bond. The delamination of silicone away from the retentive matrix is a persisting
      problem in implant-supported maxillofacial prosthesis. AIM: This study aimed to
      evaluate the effect of laser etching on the shear bond strength (BS) between
      acrylic resin and maxillofacial silicone, after 24 h of fabrication and after 200
      h of accelerated aging. MATERIALS AND METHODS: The samples were prepared
      according to ISO/TR 11405:1994 in maxillofacial silicone and polymethyl
      methacrylate resin. The untreated samples were Group A (control), Group B
      (silicon carbide [SiC] paper abrasion 80 grit size), and Group C (erbium-doped
      yttrium aluminum garnet laser etching). Then, the samples were coated with primer
      and bonded to maxillofacial silicone. The samples were subjected to shear BS test
      in an universal testing machine after 24 h of fabrication and after 200 h of
      accelerated aging. RESULTS: The results were statistically analyzed using one-way
      ANOVA and Tukey's HSD post hoc test. The shear BS test after 24 h of fabrication
      showed better BS in SiC paper abrasion. The shear BS test after 200 h of
      accelerated aging showed better BS in laser etching compared to SiC abrasion.
      CONCLUSION: Laser etching produced better shear BS compared to conventional SiC
      paper abrasion after 200 h of accelerated aging process.

PMID- 29072211
TI  - Is accredited social health activists' basic oral health knowledge appropriate in
      educating rural Indian population?
AB  - INTRODUCTION: Accredited social health activists (ASHAs) are the grassroot level
      health activists in the community who are involved in health education and
      community mobilization toward utilizing the health services. MATERIALS AND
      METHODS: A descriptive cross-sectional study was carried out to assess the oral
      health knowledge among ASHAs working in Guntur district of Andhra Pradesh, India.
      Five Primary Health Centers were randomly selected, and the total sample was 275.
      Categorical data were analyzed using Chi-square test. P <= 0.05 was considered to
      be statistically significant. RESULTS: The mean age was 32 +/- 5.11 years and
      mean education was 9 +/- 1.329 years of schooling. ASHAs were categorized into
      two groups based on their education levels, i.e., Group I whose education
      qualification is <10th class and Group II whose education qualification is above
      10th class to observe any difference in knowledge based on their education.
      Overall knowledge among ASHAs was poor and also it was observed that both the
      groups were having poor knowledge regarding dental caries, calculus, dental
      plaque, oral cancer, and change of tooth brush. About 69.5% of the ASHAs were
      approached by public with dental problems, but only a few, i.e., 15.8% have
      referred the patients to the nearby dentist. CONCLUSION: As we know that most of
      the dental diseases are preventable, there is a dire need that ASHAs should be
      thoroughly educated in the aspects of oral health and diseases during their
      training period. This not only helps in creating awareness among them but also
      serves the ultimate purpose of improving the oral health of rural population.

PMID- 29072212
TI  - Prevalence of hyperglycemia and risk factors for orodental disease in Nigeria:
      Implications of opportunistic screening.
AB  - BACKGROUND: Diabetes mellitus (DM) is associated with complications and orodental
      disease. Whether screening for DM during orodental health visits is a potential
      option is yet to be established in Nigeria. This study aims at assessing the
      prevalence of hyperglycemia in orodental disease as a clinical scenario to
      capitalize for opportunistic screening. MATERIALS AND METHODS: This study was
      undertaken in Catholic Hospital Abbi for Ndokwa communities and dental clinic of
      Eku Baptist Government Hospital, all in Nigeria. However, 474 individuals (433
      community-based and 41 dental clinic-based) including 10 orodental cases were
      screened for hyperglycemia and waist-hip circumference indices. Blood lipid
      profiles were also performed. Based on fasting blood glucose levels, participants
      were grouped into non-diabetic (n = 172), prediabetic (n = 168), and diabetic (n
      = 78). A World Health Organization questionnaire on oral health was used to
      collect information on orodental disease risk factors. Data were analyzed with
      IBM SPSS 22 statistical package. RESULTS: In the community-based cohort, the
      prevalence of hyperglycemia was 56.8%, including 38.8% prediabetes and 18.0%
      undiagnosed DM (UDM). In the dental-based group, 63.4% were hyperglycemic
      including 53.7% prediabetes and 9.7% UDM. There was significant difference (P <
      0.05) in the ages of the participants in relation to glycemic status, with 17-29
      years having the highest prevalence of UDM. However, 42.5% of the community-based
      clients had indication(s) of orodental disease. CONCLUSION: This is probably the
      first study to highlight higher prevalence of hyperglycemia from screening at a
      dental setting compared to general clinic. Opportunistic screening of DM in
      dental settings may be an option to consider during clients' orodental health
      visits.

PMID- 29072213
TI  - Efficacy of subgingival irrigation with 10% povidone-iodine as an adjunct to
      scaling and root planing: A clinical and microbiological study.
AB  - BACKGROUND: To evaluate the effectiveness of subgingival irrigation with 10%
      povidone-iodine as an adjunct to scaling and root planing (SRP) and to assess the
      effectiveness of 10% povidone-iodine in reducing periodontal pathogens mainly
      Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa).
      METHODOLOGY: Sixty patients with chronic periodontitis of mild to moderate type
      with periodontal pocket depths (PDs) of 4-6 mm were recruited. At baseline,
      plaque index, gingival index, and bleeding index were assessed. The PD and
      clinical attachment level were assessed using the Florida probe(r). Pooled
      subgingival plaque samples were collected. Each participant was allocated into 2
      arches, maxillary arch received SRP alone and mandibular arch received SRP with
      10% of povidone-iodine irrigation at baseline. After 3 months, same clinical
      parameters were assessed and plaque samples were collected from both arches. The
      collected plaque samples were evaluated using polymerase chain reaction. Data
      were analyzed using SPSS software, version 10 and through independent-samples t
      test, paired-samples t-test, and repeated measures ANOVA. RESULTS: At 3 months
      posttreatment, subgingival irrigation with povidone-iodine together with SRP
      showed a statistically significant reduction in all the clinical parameters and
      in levels of Pg and Aa. CONCLUSION: In the present study, 10% povidone-iodine
      irrigation as an adjunct to SRP favored the nonsurgical periodontal therapy, due
      to its broad-spectrum antimicrobial activity. Hence, it could be considered as an
      adjunctive treatment approach in the treatment of chronic periodontitis.

PMID- 29072214
TI  - Self-perception of patients after periodontal treatment: A longitudinal study.
AB  - AIMS: To investigate the perceptions of subjects regarding nonsurgical
      periodontal treatment over a period of 1 year. SETTINGS AND DESIGN: This is a
      secondary analysis of a randomized clinical trial, in a longitudinal
      observational design. METHODS: Nineteen subjects (47.24 +/- 6.47 years) with
      moderate to severe periodontitis completed a questionnaire at two different times
      after a nonsurgical periodontal treatment: 30 (T1) and 390 days (T2). The
      questionnaire with 40 items was divided into three domains: 1-perception of
      changes in clinical signs of periodontal disease, 2-psychological aspects of the
      subject regarding their oral health status, and 3-satisfaction with the
      treatment. STATISTICAL ANALYSIS: Each response on the Likert scale initially
      showed scores ranging from 1 to 5 points. The results for each question were
      dichotomized into 1 or 0, respectively, showing if the subject was favorable or
      unfavorable to treatment. A descriptive data analysis was performed, assessing
      the agreement of the results in T1 and T2 (Kappa). RESULTS: The results generally
      showed a favorable perception related to the treatment and continued satisfaction
      over time. The exceptions were in regards to gingival recession, persistent
      bleeding and bad breath, and difficulty in performing the mechanical control
      imposed by the professional. CONCLUSION: It was concluded that the therapy used
      was satisfactory to the subjects and that a favorable perception was maintained
      after 1 year of follow-up.

PMID- 29072215
TI  - Modified lateral positioned flap with platelet-rich fibrin graft for treatment of
      denuded root surfaces: A clinical study.
AB  - BACKGROUND: Root coverage (RC) procedures such as lateral positioned flap (LPF)
      have been used since long time but with limited success and specific indications.
      AIM: This prospective clinical study was designed to evaluate clinically the
      effect of modified LPF (mLPF) with platelet-rich fibrin (PRF) graft for the
      treatment of denuded root surfaces. MATERIALS AND METHODS: Fifteen isolated
      Miller's Class I and II gingival recession of single-rooted teeth were selected
      for the study. Scaling and root planing was done, and oral hygiene instructions
      were given to the patients. Plaque index, gingival index, and recession
      parameters (probing depth, gingival recession height, clinical attachment level
      [CAL], and width of keratinized tissue [WKT]) were assessed at baseline.
      Following this, mLPF with PRF was done at the recession sites, and parameters
      were assessed at 3 and 6 months. STATISTICAL ANALYSIS: To analyze the
      posttreatment effect, paired t-test was performed at relevant degrees of freedom
      and 95% confidence level. RESULTS: The mean percentage of RC attained was 72.2%
      at 3 months and 73.5% at 6 months. The WKT shows a mean gain of 2.93 mm at 3
      months and 3 mm at 6 months. CONCLUSION: mLPF with PRF produced statistically
      significant reduction in recession depth and gain in both CAL and WKT by the end
      of 6 months.

PMID- 29072216
TI  - Profile changes following orthodontic treatment of class I bimaxillary protrusion
      in adult patients of Dravidian ethnicity: A prospective study.
AB  - AIM: To prospectively evaluate soft and hard tissue responses to orthodontic
      treatment of bimaxillary protrusion (BMP) in Dravidian population using
      McLaughlin, Bennett, and Trevisi (MBT) mechanics of the preadjusted edgewise
      appliance. METHODS: Thirty-one adult (18-30 years) Class I BMP patients were
      treated using the above mechanics after extraction of four first premolars. Forty
      five pre- and post-treatment variables on lateral cephalograms were compared
      using paired t-test and Pearson's correlation coefficient. RESULTS: All linear
      and angular parameters pertaining to hard and soft tissues showed significant
      changes, indicating retraction of incisors, upper and lower lips; increase in
      nasolabial angle; and decrease in circumoral convexity, interlabial gap, and lip
      thickness. Various correlations established were (1) upper lip to upper incisor
      retraction 1:2.01, (2) lower lip to upper incisor retraction 1:1.5, (3) lower lip
      to lower incisor retraction 1:1, and (4) upper incisor retraction to nasolabial
      angle 1:2.02. CONCLUSIONS: Orthodontic therapy using MBT mechanics is very useful
      in achieving favorable hard and soft tissue changes, following four first
      premolar extractions in BMP. The various correlations established between incisor
      retraction and soft tissue parameters could prove useful to the discerning
      clinician.

PMID- 29072217
TI  - Assessment of quality of life of patients 1-5 years after treatment for oral
      cancer.
AB  - PURPOSE: The study aims to assess the quality of life (QOL) of oral cancer
      survivors, 1-5 years after the treatment. MATERIALS AND METHODS: The data of
      fifty patients concerning their QOL were gained from the Outpatient Department of
      K.L.E's Dr. Prabhakar Kore Hospital and Medical Research Institute, Belagavi, and
      Karnataka Cancer Therapy and Research Institute, Navanagar, Hubli, Karnataka,
      India. All the patients suffered from oral cancer (stage T2-T4) and underwent
      surgery with reconstruction followed by chemotherapy or radiotherapy or both. The
      patients completed the standard European Organization for Research and Treatment
      of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C-30 (version 3.0) and QLQ
      Head and Neck Cancer Specific (QLQ H and N-35) (version 1.0). Scoring was done
      according to the EORTC scoring manual. RESULTS: The mean age at the time of
      diagnosis was 45.0 (+/-9.0). The study population had a mean global health status
      (GHS) for overall QOL of 55.5 +/- 13.4.The mean functional scale (FS) was 87.5
      (+/-9.6).The mean QLQ C-30 symptom scale (SS) was 16.3 (+/-11.9) and the mean QLQ
      H and N-35 SS (H and NSS) was 26.9 +/- 11.5. Location, gender, age, and time
      after the treatment showed very less discrepancy in the group comparisons of GHS,
      FS, SS, and H and NSS whereas comparison based on T-stage showed significant
      difference in scores. CONCLUSION: Oral cancer has a significant impact on the QOL
      of the patients. Assessment of QOL should receive adequate attention in treatment
      planning and rehabilitation. This would definitely help in delivery of better
      symptom directed therapies and improve the QOL of the patients.

PMID- 29072218
TI  - Study of lip prints in different ethno-racial groups in India.
AB  - : Context (Background): Lips prints are unique and are a tool for personal
      identification. AIMS: Indian population can be divided into different ethno
      racial groups. In this study, we aimed at finding the most and the least
      prevalent lip print patterns in these groups and also to observe any similarities
      or differences that may exist in these groups in terms of lip print patterns.
      SETTINGS AND DESIGN: Lip prints in 755 individuals categorized into different
      ethno-racial groups were studied. MATERIALS AND METHODS: Brown- and pink-colored
      lipsticks, cellophane tape, and magnifying lens were used to record and study the
      lip prints. RESULTS: Among all the three ethno-racial groups, Type I was the most
      prevalent lip print pattern observed. The least prevalent lip print pattern in
      all the three groups was Type IV. Inference/Conclusion: Lip prints hold potential
      as supplementary tools for identification where they can be recorded with ease.
      The observation and classification of lip print patterns in different ethno
      racial groups not only provide some useful data but also open a new window to a
      field that can contribute extensively to criminal investigation and
      identification.

PMID- 29072219
TI  - Correlation of mucocutaneous manifestations of HIV-infected patients in an ART
      center with CD4 counts.
AB  - BACKGROUND: As the search for reliable clinical indicators for management of
      human immunodeficiency virus/AIDS continues, mucocutaneous manifestations of HIV
      are considered among key clinical indicators for prediction of underlying degree
      of immunosuppression, systemic opportunistic infections, and disease progression.
      OBJECTIVES: (1) To study the prevalence of mucocutaneous manifestations in HIV
      seropositive patients attending the ART center of our hospital (2) To correlate
      mucocutaneous manifestations with CD4 cell counts. MATERIALS AND METHODS: A total
      of 200 HIV-seropositive patients of adult age group visiting our hospital were
      included in the study. Information on demographics such as age, sex, transmission
      route, socioeconomic status, educational status, CD4 counts, and mucocutaneous
      findings was collected through interview administered survey and case records
      followed by oral and cutaneous examination. RESULTS: Mean CD4 cell count of
      asymptomatic HIV/AIDS patients was 580.96 cells/mm3. In comparison with the CD4
      cell count of asymptomatic HIV-positive patients, (mean 580.96 cells/mm3) CD4
      cell count of HIV-positive patients with various mucocutaneous manifestations
      (mean 409.65 cells/mm3) was correlated using student t-test and was statistically
      significant (P = 0.017). CONCLUSION: This study revealed maximum mucocutaneous
      lesions in the CD4 count range of 200-500. Nail changes accounted for the most
      common cutaneous manifestation with 53%, and pigmentation accounted for the most
      common oral manifestation with 39%. Mucocutaneous manifestations can arouse one
      to suspect the diagnosis of HIV infection in an otherwise healthy unwary patient.
      They can serve as a dependable marker of HIV disease.

PMID- 29072220
TI  - Microbial assessment of dental unit waterlines in an institutional setup in
      Karnataka, South India.
AB  - BACKGROUND AND AIM: Biofilms in dental unit waterlines (DUWLs), suction hoses,
      and fittings are a potentially significant source of cross-contamination posing
      significant health risk as these may come into contact with patients during
      treatment. The purpose of this in vitro study was to identify the spectrum of
      bacterial flora colonizing the DUWLs and to detect pathogenic microorganisms
      present in such an environmental niche. MATERIALS AND METHODS: Thirty DUWL
      samples were collected from in use dental units selected randomly from various
      clinical departments. Samples were collected from the following devices; 3-in-1
      syringe waterline, section of waterline tubing supplying the 3-in-1 syringe, and
      the air rotor water. The samples were subjected to bacteriological analysis, and
      all bacterial isolates were tested for their ability to form biofilms. RESULTS: A
      descriptive analysis of the results obtained was carried out, and it was observed
      that 7 out of 30 (23.3%) samples collected from DUWL were supplying water of
      unsatisfactory quality with species of low-pathogenicity bacteria isolated
      present in significant numbers; four of ten (40%) water supply lines contained
      bacterial biofilms; and the species with greatest capability to form biofilms
      were Enterobacter species (spp.). In addition, the results were also subjected to
      Chi-square test which revealed no statistical difference between the species and
      the location of collection of samples. CONCLUSION: Within the limitations of this
      study, it is concluded that DUWLs are not totally free of contamination.
      Microbial biofilms are a significant source of cross-contamination and cross
      infection in the dental clinic environment.

PMID- 29072221
TI  - Comparative evaluation of inhibitory effect of curcumin and doxycycline on matrix
      metalloproteinase-9 activity in chronic periodontitis.
AB  - BACKGROUND AND OBJECTIVES: The pathogenesis of inflammatory periodontal diseases
      essentially involves degradation of extracellular matrix molecules, and collagen
      breakdown and matrix metalloproteinases (MMPs) are proteinases primarily involved
      in this process. It is known that doxycycline downregulates MMP activity.
      Curcumin has anti-inflammatory effect and also downregulates MMP activity. Thus,
      a study was conducted to evaluate the anti-inflammatory effect of curcumin by its
      inhibition of MMP-9 activity and compare the same with doxcycline, which has
      known anticollagenase activity. SUBJECTS AND METHODS: Gingival tissue samples
      were obtained from thirty patients diagnosed with chronic periodontitis. The
      tissue extracts were treated with Curcumin and doxycycline and inhibition of MMP
      9 analyzed by gelatinzymography. Gels obtained were stained with Coomassie
      Brilliant Blue, and enzymatic activities detected as bands of gelatinlysis
      against blue background. Relative MMP-9 levels were measured by scanning the
      clear zones and analyzing the percentage inhibition. RESULTS: Results showed that
      MMP-9 activity was significantly decreased by both the drugs. Curcumin showed
      61.01% reduction in the MMP-9 activity at 1500 MUg/ml concentration and
      doxycycline showed 59.58% reduction in the MMP-9 activity at 300 MUg/ml
      concentration. CONCLUSION: The current study showed that curcumin has inhibitory
      effect on polymorphonuclear leukocyte-type MMP-9 involved in matrix degradation
      in periodontitis. Since Curcumin has a potent anti-inflammatory effect, it may
      have therapeutic potential as a host modulation agent in periodontal diseases.

PMID- 29072222
TI  - Effects of at-home and in-office bleaching agents on the shear bond strength of
      metal, ceramic, and composite brackets to enamel.
AB  - AIMS AND OBJECTIVES: This study aimed to evaluate the effects of at-home and in
      office bleaching on the shear bond strength (SBS) of metal, ceramic, and
      composite orthodontic brackets and to compare their SBSs. SUBJECTS AND METHODS: A
      total of 96 human lower premolar teeth were used for this study. Six teeth were
      used for scanning electron microscopic study while the remaining ninety were
      divided into three equal groups. Each group was further subdivided into three
      subgroups with ten samples each. Three protocols were used. In the at-home
      bleaching group (n = 30), opalescence non-PF (potassium nitrate and fluoride)
      bleaching agent (10% carbamide peroxide) was applied onto the teeth daily for 14
      days and left for 8 h each day. Teeth in the in-office group (n = 30) were
      treated twice in consecutive days with Opalescence boost PF (40% hydrogen
      peroxide). After bleaching, the specimens were stored in distilled water for 1
      day before bonding. SBS testing was performed on all teeth using Instron
      universal testing machine. RESULTS: Analysis of variance indicated a significant
      difference (P < 0.005) among the groups. Maximum SBS was shown by ceramic
      brackets in control group (Ib) and minimum was shown by composite brackets of in
      office bleached group (IIIc). CONCLUSIONS: The results showed that at-home
      bleaching did not affect the SBS significantly whereas in-office bleaching
      reduced SBS of metal, ceramic, and composite brackets significantly. It is
      preferable to use metal or ceramic brackets than composite brackets for bonding
      24 h after bleaching.

PMID- 29072223
TI  - Telomerase: An exploration toward the end of cancer.
AB  - BACKGROUND: The distinguishing feature of cancer cells is their ability to
      proliferate indefinitely, which is in contrast to the restricted cell
      multiplication potential for somatic cells. A better understanding of this
      contrasting behavior was provided in the early 1990s with the discovery of a
      relationship between telomeres, telomerase, aging, and cancer. Telomeres (tandem
      repeat DNA sequence TTAGGG) are protective caps at the ends of human chromosomes.
      Normal human cells experience telomere shortening with each successive cell
      division. However, in tumor cells, an overexpression of telomerase confers
      limitless replicative potential to tumor cells by continuous elongation of
      telomeres. The objective of this review was to systematically assess the data
      available on telomerase expression in oral cancer, with special reference to its
      role in diagnosis, prognosis, and treatment. MATERIALS AND METHODS: A systematic
      review of studies that investigated the telomerase expression in oral squamous
      cell carcinoma (OSCC) was registered with PROSPERO. Subsequent to registration, a
      predetermined search strategy in accordance with PRISMA guidelines was
      formulated, and a literature search was conducted using online databases along
      with hand searching. RESULTS: Eighty-nine articles from PubMed, 83 from Scopus, 5
      from BioMed Central, 43 from Google Scholar, and 2 from hand search were
      identified. A total of 21 articles were shortlisted that met strict inclusion and
      exclusion criteria and quality assessment. Each study was evaluated for the
      markers under study, type of sample used, study design/methodology, and
      statistical analysis. The studies were then grouped into three subheads depending
      on their implications in the diagnosis, prognosis, and treatment of OSCC.
      CONCLUSION: This review explains the basic biology and the clinical implications
      of telomerase-based diagnosis and prognosis, the prospects for its use in
      anticancer therapy, in the context of oral cancer.

PMID- 29072224
TI  - Ankyloglossia: Surgical management and functional rehabilitation of tongue.
AB  - Ankyloglossia or "tongue-tie" is a rare congenital anomaly characterized by an
      abnormally short, thick, fibrosed lingual frenulum which may cause restriction in
      function of tongue including limitation in tongue movement. The lingual frenulum
      may be fibrous or muscular, and the tie may be complete or partial. Most often,
      ankyloglossia is seen as an isolated condition in an otherwise normal individual.
      This article reports the surgical management of a 20-year-old patient having
      ankyloglossia associated with restricted movement of tongue and difficulty in
      speech. The treatment involved is surgical removal of the lingual frenum followed
      by tongue training exercise and speech therapy to functionally rehabilitate the
      tongue. Six months postoperatively, the patient showed uneventful healing and was
      satisfied with the procedure.

PMID- 29072225
TI  - Bilateral pediatric mandibular distraction for micrognathia with
      temporomandibular joint ankylosis and sleep apnea.
AB  - Mandibular retrognathism is one of the important contributing anatomical factors
      to the obstructive sleep apnea (OSA). Such patients suffer from number of apneic
      or hypopneic events during sleep such as snoring, daytime sleepiness, fatigue,
      inability to concentrate, and irritability. Distraction osteogenesis is a less
      invasive surgical technique in the management of OSA by correcting the reduced
      airway space. Apart from correcting functional disturbances due to OSA, it also
      corrects the facial profile resulting in the substantial improvement in cosmetic
      appearance. We report a case of a 3-year-old boy who was struggling with severe
      retrognathic chin and OSA causing hypopneic episodes and snoring. He was
      successfully treated by bilateral mandibular distraction which resulted in
      significant improvement of respiratory distress and feeding as well as evidential
      advancement of the mandible was achieved.

PMID- 29072226
TI  - Retrospective morphometric analysis of the infraorbital foramen with cone beam
      computed tomography.
AB  - OBJECTIVE: The aim of our study is to examine the morphometric characteristics of
      the infraorbital foramen (IOF) and its anatomic localization by using cone-beam
      computerized tomography (CBCT). MATERIALS AND METHODS: In our study, the anatomic
      characteristics of the IOF were identified by studying retrospectively the CBCT
      images of one hundred twenty-five (125) patients. These characteristics were
      assessed statistically in terms of age, gender, and right-left side. RESULTS: In
      our study, 42% of them had IOF in circular form and 58% in oval form. Of them
      66.90% of those in oval form were in oblique direction, 28.30% of them were in
      vertical direction, and 4.80% of them were in horizontal direction. The mean
      vertical diameter of the IOF was found as 3.71 +/- 0.61 mm and its mean
      horizontal diameter was found as 3.17 +/- 0.56 mm. The mean distance of IOF to
      midline were measured as 25.10 +/- 2.17 mm, distance to upper edge of the orbita
      was measured as 41.91 +/- 2.77 mm, distance to infraorbital edge was measured as
      5.63 +/- 1.77 mm, distance to the lateral nasal wall was measured as 9.32 +/-
      2.68 mm, distance to spina nasalis anterior was measured as 17.97 +/- 3.99 mm,
      thickness of the soft tissue on the foramen was measured as 11.52 +/- 2.40 mm,
      and distance between the right and the left IOF was measured as 50.20 +/- 3.90
      mm. Accessory foramen was found in 56.60% ratio. CONCLUSION: This study reveals
      that CBCT may guide for local anesthesia applications and for other invasive
      procedures in order to prevent the damage of the neurovascular structures during
      maxillofacial surgery by identifying the distances of anatomic points such as IOF
      having surgically importance.

PMID- 29072227
TI  - Cancer patients and oncology nursing: Perspectives of oncology nurses in Turkey.
AB  - BACKGROUND AND AIM: Burnout and exhaustion is a frequent problem in oncology
      nursing. The aim of this study is to evaluate the aspects of oncology nurses
      about their profession in order to enhance the standards of oncology nursing.
      MATERIALS AND METHODS: This survey was conducted with 70 oncology nurses working
      at Hacettepe University Oncology Hospital. Data were collected between January
      April 2012. Each participant provided a study form comprising questions about
      sociodemographic information; about difficulties, positive aspects and required
      skills for oncology nursing; and questions evaluating level of participation and
      clinical perception of oncology nursing. RESULTS: Mean age of nurses was 29.9 +/-
      5.7 years. More than half of the participants were married (51.4%) and 30% had at
      least one child. Percent of nurses working in oncology for their entire work life
      was 75.8%. Most frequently expressed difficulties were exhaustion (58.6%), coping
      with the psychological problems of the patients (25.7%), and frequent deaths
      (24.3%); positive aspects were satisfaction (37.1%), changing the perceptions
      about life (30%), and empathy (14.3%); and required skills were patience (60%),
      empathy (57.1%), and experience (50%). For difficulties of oncology nursing,
      28.3% of difficulties could be attributed to job-related factors, 30.3% to
      patient-related factors, and 77% of difficulties to individual factors. The
      independent predictors of participation level of the nurses were self-thoughts of
      skills and positive aspects of oncology nursing. CONCLUSION: According to the
      findings of this study, nurses declared that working with cancer patients
      increase burnout, they are insufficient in managing work stress and giving
      psychological care to patients, but their job satisfaction, clinical skills and
      awareness regarding priorities of life has increased.

PMID- 29072228
TI  - An audit of endometrial hyperplasias at the Lagos University Teaching Hospital.
AB  - INTRODUCTION: There has been much controversy and confusion surrounding the
      endometrial hyperplasias stemming from the use of a wide variety of terminologies
      and also from the pathophysiologic mechanisms underlying the various entities.
      The current classification by the World Health Organization (WHO) published in
      2014 clarifies these issues. OBJECTIVE: The aim of this study, therefore, was to
      audit and standardize cases of endometrial hyperplasia diagnosed in our
      institution from 2007 to 2011. MATERIALS AND METHODS: The slides and request
      forms of cases diagnosed as endometrial hyperplasias at the Department of
      Anatomic and Molecular Pathology from January 1, 2007, to December 31, 2011 were
      retrieved, reviewed, and reported according to the WHO 2014 classification
      scheme. RESULTS: Hyperplasia without atypia accounted for the vast majority of
      cases (95.5%) and was the most common in the 5th decade. Concordance rates of
      74.5% and 100% were found between endometrial hyperplasias without atypia and
      atypical hyperplasias with their previous diagnoses, respectively. CONCLUSION:
      The WHO classification scheme standardizes and simplifies the terminology used in
      the diagnosis of endometrial hyperplasias, while reflecting, at the same time,
      the current understanding of genetic changes that provide information necessary
      for prognostication and treatment.

PMID- 29072229
TI  - Predictors of male condom utilization in Plateau State, Nigeria.
AB  - BACKGROUND: Nigerian men play major roles in the reproductive decision-making
      process, including issues concerning fertility. Despite efforts made by the
      government to reduce the incidence of HIV by using condom as a means of dual
      protection, the utilization of male condom is still relatively low in Nigeria.
      This study aimed to assess the condom utilization and predictors of condom use
      among male respondents in Plateau State. METHODOLOGY: An analysis of secondary
      data of the 2013 Nigeria Demographic Health Survey dataset was done. Data were
      collected through a cross-sectional study using multistage cluster sampling
      technique from 393 consenting males aged 15-49 years in Plateau State using a
      semistructured, closed-ended questionnaire. Survey data quality was ascertained
      using field check tables during data entry. The dataset was analyzed using SPSS
      version 21.0 software (SPSS, IBM Corp, Armonk, NY, USA). Condom utilization
      prevalence rate was calculated for the 393 males, while predictors were
      determined by logistic regression. P <= 0.05 was considered statistically
      significant. RESULTS: Mean age of the respondents was 31.05 +/- 9.395 years. Most
      (90.3%) of the respondents were aware of at least one of the various family
      planning methods. The prevalence of condom use among them was 15.5% with the 20
      29 years' age group having the highest proportion (28.8%). Significant
      associations were found between condom use and age, level of wealth, level of
      education, marital status, knowledge of contraception, occupation, and religion.
      Predictors of condom use include level of wealth (middle class), not being
      married, and primary level education. CONCLUSIONS: The prevalence of male condom
      use is low in Plateau State. The predictors of condom use are level of wealth,
      being unmarried, and primary level of education. Having only a primary level of
      education and been in the middle class reduces the likelihood of using condoms
      while being unmarried increases it.

PMID- 29072230
TI  - A survey of the perception of the quality of and preference of healthcare
      services amongst residents of Abeokuta South Local Government, Ogun State,
      Nigeria.
AB  - BACKGROUND: The choice of healthcare facilities by individuals is determined in
      part by their taste, satisfaction with services, and the perceived quality of
      care provided. The aim of the study was to explore the healthcare preferences of
      residents of Abeokuta South Local Government Area (LGA) and their perception of
      quality of services received, and to determine the factors influencing their
      choice of healthcare facilities. MATERIALS AND METHODS: A descriptive cross
      sectional study design was used to assess perception of clients regarding quality
      of healthcare received and their choice of healthcare service delivery. Data were
      collected using a pre-tested interviewer-administered questionnaire, and analysis
      was done using SPSS version 17. Statistical significance was set at P <0.05.
      RESULTS: The mean age of respondents was 45.7 +/- 11.7 years. Government-owned
      general hospitals were preferred for common health problems such as body pain and
      fever. Overall, about 73% of the respondents preferred government-owned
      facilities. Determinants of the preference of the government facilities were
      reduced cost (P< 0.001) and effectiveness of care (P= 0.024), whereas private
      facilities were preferred more significantly because of short waiting time and
      good attitude of staff (P = < 0.001). Almost 78% of the respondents were
      satisfied with the quality of care received. CONCLUSIONS: Government-owned
      general hospitals were the preferred source of health services and the quality of
      healthcare services received was generally perceived to be high.

PMID- 29072231
TI  - Evaluation of drug utilization pattern for patients of bronchial asthma in a
      government hospital of Saudi Arabia.
AB  - BACKGROUND: Bronchial asthma is a social and economic healthcare burden. Drug
      utilization studies are important tools to assess current prescription practices
      against standard guidelines and help in rationalizing the management. MATERIALS
      AND METHODS: This retrospective cross-sectional study was designed to evaluate
      the pattern of drug utilization in bronchial asthma patients in a government
      hospital of Saudi Arabia. Retrospective prescribing information of patients of
      all ages and both sexes diagnosed with bronchial asthma being treated with at
      least one of the anti-asthmatic medications was utilized. Demographic details,
      brand/generic name, indication, route, dosage, frequency, and date of starting
      the drug were recorded. Prescriptions were examined for order, number, and
      therapeutic class of drugs in addition to poly-pharmacy and appropriateness.
      Patients having other respiratory disorders such as chronic obstructive pulmonary
      disorder (COPD), bronchitis, emphysema, or any comorbidity such as diabetes,
      hypertension, and peptic ulcer were excluded. The Statistical Package for the
      Social Sciences was used for statistical analysis. RESULTS: A total of 380
      prescriptions were studied. Patients were aged from 4 months to 79 years, with
      55.3% males and 44.7% females. Pediatric prescriptions were 47.4%.
      Bronchodilators followed by steroids were the most common drug groups. Salbutamol
      and budesonide were the most common from each group, respectively. 89.5% of the
      patients were having at least two drugs. Number of drugs per prescription
      averaged 3.18 +/- 1.22, however, no correlation was found between different age
      groups and number of drugs. 61.3% drugs were administered by inhalational route
      and 34.8% by oral route. Approximately 77.2% prescriptions were found to be
      appropriate. CONCLUSION: Prescription pattern was mainly in accordance with
      standard guidelines with some knowledge and technical gaps in prescription
      writing methodology.

PMID- 29072232
TI  - Comparison of medial and posterior surgical approaches in pediatric supracondylar
      humerus fractures.
AB  - OBJECTIVES: The aim of the current study was to compare the clinical results of
      pediatric supracondylar humerus fracture cases requiring open reduction through
      medial approach with posterior approach. PATIENTS AND METHODS: Retrospective
      cohort of 67 cases of pediatric supracondylar fractures was reviewed. Thirty
      three patients (20 males, 13 female, average age: 8.3 +/- 3.131) were treated
      with medial approach were compared with 34 patients (19 males, 15 females,
      average age: 7.5 +/- 3.146) treated with posterior exposure. Median follow-up
      period of the first group was 35.04 months (range: 17-76 months) and of the
      second group was 36.04 (range: 16-65 months). Radiological evaluation included
      Baumann angle, carrying angles, and lateral humero-capitellar angles. Functional
      and cosmetic evaluation was assessed with range-of-motion measurements and the
      criteria defined by Flynn et al. RESULTS: No differences between groups were
      noted regarding gender, age, and follow-up periods. Operative time was
      significantly shorter in medial approach group [60.0 +/- 14.5 vs. 75.8 +/- 17.6
      min (P = 0.002)]. Radiological measurements (Baumann, humero-capitellar, and
      carrying angles) were also similar between groups. When evaluated patients
      according to Flynn's criteria, for medial group, 31 cases (93.9%) had good
      perfect result regarding ROM loss, whereas for posterior group 33 cases (97%) had
      good-perfect result. Regarding carrying angle change and posterior group were
      slightly better than medial group (perfect result observed in 91.1% vs 81.8%,
      respectively). The differences did not show statistical significance. CONCLUSION:
      In the treatment of supracondylar humerus fractures in children, both surgical
      approaches revealed similar functional and radiological outcomes with shorter
      operative time when medial approach was utilized.

PMID- 29072233
TI  - Effects of parental attitudes on the use of addictive substances in high school
      students.
AB  - BACKGROUND: Substance abuse is a major public health problem including social and
      economic aspects. Although multidimensional data about substance abuse are
      limited in our country, the fact that Turkey is located at the crossroads of
      Europe and Asia with a young population creating a promising market brings out
      the necessity of maintaining high awareness on substance abuse. Smoking, alcohol,
      and substance use are important health problems of adolescence period and
      families play a major role on adaptation to the changes in growth and development
      period. The research on substance abuse and dependence emphasizes on protective
      or risk-enhancing effects of family. AIMS: The aim of this study was to provide
      evidence on the interventions that could be implemented about substance use by
      evaluating the relationship between parental attitude and attitudes of high
      school students toward substance use. STUDY DESIGN: This was a survey study.
      MATERIALS AND METHODS: The study included randomly selected high school students
      who were willing to participate in the study from Ankara province. The students
      were applied the sociodemographic information questionnaire especially prepared
      for this research, the Addictive Substances Attitudes Scale for high school
      students, and the Parental Attitudes Scale. RESULTS: In the study, data of 707
      students, 311 boys and 396 girls, with a mean age of 16.1 years were evaluated.
      According to the obtained findings, the rate of students with a negative attitude
      toward addictive substances increases as parental attitude changes from
      authoritative attitude to democratic attitude. CONCLUSION: The present study
      demonstrated that parental attitudes are related with the attitudes of high
      school students toward addictive substances. Students mostly adopted a negative
      attitude toward substance use in case of democratic parental attitude. Therefore,
      to protect children from substance abuse, parents should be advised to adopt a
      democratic attitude characterized with sincere love and constructive control.

PMID- 29072234
TI  - Occult metabolic bone disease in chronic pancreatitis.
AB  - BACKGROUND: Chronic pancreatitis (CP) leads to malabsorption and metabolic bone
      disease (MBD). Alcoholic CP (ACP) and tropical CP (TCP) are the two common types
      of CP. OBJECTIVE: We investigated the presence of occult MBD in patients with CP
      and compared the same between ACP and TCP. MATERIALS AND METHODS: In this cross
      sectional, observational study, we included serial patients of CP in different
      stages and are grouped as ACP (Group 1; n = 67) and TCP (Group 2; n = 35). We
      determined serum calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D
      (25OHD), and intact parathyroid hormone (PTH) levels. Bone mineral density (BMD)
      was measured by dual-energy X-ray absorptiometry in the neck of the left femur.
      MBD was defined by the presence of either low bone mass (Z-score Results: The
      study participants (85 males; 17 females) had a mean age of 40.8 +/- 12.6 years,
      CP duration of 3.7 +/- 4.7 years, and Body Mass Index of 22.5 +/- 3.2 kg/m2. A
      total of 37 (36%) patients had MBD (osteomalacia in 31 and low bone mass in 6).
      The frequency of MBD was same in the TCP (16/35) and ACP (21/65) groups (P =
      0.1940). Elevated PTH (>70 pg/mL) was seen in 14 patients with 25OHD deficiency
      and low calcium (<8.5 mg/dL) in 29 patients. BMD did not show a significant
      correlation with the duration of CP. CONCLUSION: Occult MBD is seen in a third of
      patients with CP and is similar irrespective of the etiology. The disease is
      silent and mandates active screening in all susceptible individuals.

PMID- 29072235
TI  - Reconstruction of lower extremity primary malignant and metastatic bone tumours
      with modular endoprosthesis.
AB  - INTRODUCTION: This study is aimed to assess the functional results of cases with
      lower extremity malignant and metastatic bone tumours that were treated with
      modular tumour resection prostheses. MATERIALS AND METHODS: 49 patients were
      retrospectively examined. 27 (55.1%) patients had a primary bone tumour, and 22
      (44.9%) had a metastatic bone tumour. Although most tumours located in the
      proximal femur were metastatic, tumours located around the knee were mostly
      primary malignant bone tumours. The functional assessments of our patients were
      made according to the Musculoskeletal Tumour Society (MSTS) scoring system. The
      Student's t-test and the Chi-square test were used for statistical analyses.
      RESULTS: 30 (61.2%) of the patients were men, and 19 (38.8%) were women. The
      average age was 46.2 +/- 1.9 years. Tumours were located in the proximal femur in
      27 (55.1%) patients, distal femur in 16 (32.7%) patients and proximal tibia in 6
      (12.2%) patients. 14 (28.6%) patients had a pathological fracture on admission.
      The average follow-up period of our patients was 27.4 +/- 3.4 months, and the
      average MSTS score was 74.3 +/- 13%. Complications developed at any time in 34.7%
      of the patients, and the most common symptoms were aseptic loosening (8.2%) and
      prosthesis infection (8.2%). Local relapse was found in one (2%) patient. The 5
      year survival rate was 68.3% in patients with a primary tumour and 30% in
      patients with a metastatic tumour. CONCLUSION: Although endoprosthesis
      reconstruction had advantages of giving very good functional results in the early
      phases, it was found to cause mechanical complications, especially in patients
      with primary bone tumours during the mid and late phases.

PMID- 29072236
TI  - Knowledge and utilization of electrocardiogram among resident doctors in family
      medicine in Nigeria.
AB  - BACKGROUND: Electrocardiogram (ECG) is a simple, readily affordable, and
      noninvasive tool for the evaluation of cardiac disorders. There is a dearth of
      information on the utility of ECG in general practice in Nigeria. We assessed the
      knowledge and utilization of ECG among family medicine residents in Nigeria.
      MATERIALS AND METHODS: A cross-sectional evaluation was conducted between
      November 2011 and May 2012 in four family medicine training centers in Nigeria. A
      self-administered questionnaire was used to obtain information from the resident
      doctors regarding their ECG requests, preferred source of interpretation, most
      common ECG diagnosis, and update of ECG knowledge. RESULTS: Only 61 out of 120
      questionnaires (50.8%) were returned. The respondents were mostly between 31 and
      40 years (54.7%) and were predominantly males (73.8%) and senior residents
      (65.6%). Fifty-four (88.3%) respondents made <5 ECG requests/week, and the most
      common indication was hypertension (50%). ECG interpretation was either self
      reported (41%), by a cardiologist (26.5%), or automated reports (21.3%). Self
      reporting of ECG was more common among senior residents (P < 0.01). Left
      ventricular hypertrophy was the most common ECG diagnosis (55.8%). About 69% of
      respondents did not update their knowledge of ECG. Most respondents (50%)
      reported basic interpretation as the aspect of ECG for which further learning was
      desired. Teaching ECG to resident doctors in the update courses of the
      postgraduate medical colleges and continuing medical education (CME) activities
      was adjudged the best way to improve knowledge/utility (61.1%). CONCLUSION: The
      attitude to and utility of ECG among family medicine residents in Nigeria is
      poor. Improved knowledge, attitude, and utilization of ECG through curriculum
      revision, hands-on tutorials, and CMEs are highly recommended.

PMID- 29072237
TI  - Pain intensity and its objective determinants following implant surgery and sinus
      lifting: A 1-year prospective study.
AB  - OBJECTIVES: The main goal of this study was to evaluate the relationship between
      postoperative pain and short-term implant survival. Objective parameters, such as
      implant-related factors (type, diameter, length) and the surgical approach were
      also assessed to correlate them with pain. MATERIALS AND METHODS: This
      prospective, single-center study consisted of 144 patients scheduled for the
      surgical placement of one or more implants either with conventional surgery or
      with sinus-lifting together. All patients were asked to complete a questionnaire
      form of pain with a visual-analog scale (VAS, 1-10) for 7 days following surgery.
      The association of pain scores at each time-point was assessed on implant- and
      surgery-related factors. RESULTS: The overall cumulative survival rate of 546
      implants in 144 patients was 98.17 % (10 implants lost) after 1-year follow-up.
      No statistical difference was found in pain (VAS) scores between patients with
      loss and survived implants at any observation period. The length and diameter of
      placed implants and the presence of a sinus-lifting procedure did not influence
      the pain scores at any period (P > 0.05). In patients with bilateral sinus
      lifting, the decrease in pain scores was significant after 3 days (P < 0.05),
      whereas it was significant after 6 hours for the conventionally treated group (P
      < 0.01). Although no severe pain was reported at any time, this study found a
      significant difference in pain intensities among different implant brands.
      CONCLUSIONS: This study was able to show that increased postoperative pain is not
      a sign of early implant failure. In addition to this, the implant dimensions and
      presence of sinus lifting procedure did not influence the pain experience.
      However, the bilateral sinus lifting prolongs the recovery time.

PMID- 29072238
TI  - Prevalence of lupus anticoagulant in women with spontaneous abortion in Zaria.
AB  - INTRODUCTION: Spontaneous abortion (SA) is a common complication of pregnancy.
      Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, has
      been associated with SA in many studies, especially in Caucasians. This study was
      carried out to determine the prevalence of LA in women with SA in ABUTH, Zaria.
      MATERIALS AND METHODS: A cohort of 100 consecutive women presenting with SA with
      no history of thrombotic episodes were enrolled into the study. Prothrombin time
      (PT), kaolin clotting time (KCT), and activated partial thromboplastin time
      (APTT) were conducted on samples of all the participants. Eight patients had
      prolonged APTT, and after a 50:50 mixture of their plasma with pooled control
      plasma, four (50%) had uncorrected APTT. Staclot(r) (a hexagonal-phase
      phospholipid) test and calculated Rosner index for prolonged KCT were used for
      the confirmation of LA in samples with uncorrected APTT after mixing studies.
      RESULTS: We analyzed 100 women with one or more SA with a mean age of 31.0 +/-
      3.8 years. Nearly 4% and 3% of the participants were LA positive with Staclot(r)
      and KCT tests, respectively. Patients with LA were more likely to have had a past
      history of preeclampsia/eclampsia, small for gestational age deliveries, and
      previous SA (prevalence odds ratio [95% confidence interval]) of 1.9 (0.2, 20.1),
      3.2 (0.3, 34.3), and 1.4 (0.1-13.6), respectively. The PT, APTT, and KCT were
      significantly prolonged in patients with LA (P <= 0.001 for each, respectively).
      CONCLUSION: LA may be one of the causes of SA and other adverse pregnancy
      outcomes such as preeclampsia/eclampsia and small for date deliveries. It is
      recommended that patients with prolonged APTT, uncorrected with 50:50 mixing
      study with pooled control plasma, should be evaluated further for LA.

PMID- 29072239
TI  - Environmental factors that determine visual skill development of under-fives in a
      developing country.
AB  - INTRODUCTION: During the early years of life, children get most of their
      information by relying on their visual observation. Knowledge of visual skill
      development and environmental risk factors influencing it provides useful guide
      for early identification of children who may develop some form of visual
      impairment. AIM: The aim of this study is to describe the visual developmental
      pattern and determine the environmental risk factors associated with delay in the
      visual skill area of under-five children. SUBJECTS AND METHODS: This was a cross
      sectional study of 415 preschoolers aged 6-59 months. Visual function and visual
      comprehension were assessed using the Schedule of Growing Skills II tool (GL
      Assessment Ltd., London). Delay in the visual skill was defined as a
      developmental quotient in visual skill area below threshold point of 85%. Data
      were analyzed using descriptive statistics and logistic regression analysis with
      adjusted odds ratio (AOR) and 95% confidence interval (CI) (95% CI). Alpha value
      was set at P < 0.05. RESULTS: Mean age of the children studied was 32.6 +/- 15.9
      months. The prevalence of delay in visual skill area was 17.1%. The odds of delay
      in visual skill were higher among children of first birth order (AOR 1.83; 95% CI
      1.05-3.30), those who lived in large households (AOR 2.34; 95% CI 1.32-3.14),
      children whose mothers had secondary level education and below (AOR 2.21; 95% CI
      1.31-3.83), and those whose fathers earned <=$100 per month (AOR 1.75; 95% CI
      1.01-3.03). CONCLUSION: Identification and management of environmental factors
      negatively affecting visual skill development will help improve on the visual
      skill area and invariably child development.

PMID- 29072240
TI  - The role of the nasal and paranasal sinus pathologies on the development of
      chronic otitis media and its subtypes: A computed tomography study.
AB  - OBJECTIVE: This objective of this study is to evaluate the presence and the
      coincidence of common nasal and paranasal sinus pathologies in adults suffering
      from chronic otitis media (COM) and its subtypes. MATERIALS AND METHODS: The
      study group comprised 354 ears of 177 patients who underwent tympanoplasty with
      or without mastoidectomy from January 2013 to February 2015 due to uni/bilateral
      COM. Chronic suppurative otitis media, intratympanic tympanosclerosis (ITTS),
      cholesteatoma, and tympanic membrane with retraction pockets constituted subtypes
      of COM. The control group consisted of 100 ears of 50 adult patients with aural
      diseases other than middle ear problems. All patients were evaluated for the
      evidence of mucosal disease on paranasal sinuses, the presence of concha bullosa
      (CB), and the angle of nasal septal deviation (NSD) and thickness of the medial
      mucosa of the inferior turbinate were measured by coronal computed tomography
      images. RESULTS: The incidence and the angle of NSD were found significantly
      higher in patients with COM (P = 0.028, P = 0.018; respectively). When ears with
      unilateral and bilateral COM compared in term of sinonasal pathologies, CB was
      found higher in patients with unilateral COM (P = 0.040). The presence of CB was
      significantly higher in ITTS when compared to other subtypes (P = 0.028).
      CONCLUSIONS: Our study suggests that obstructive nasal pathologies such as NSD
      and CB may play a role in the pathogenesis of especially unilateral COM. However,
      there was no correlation between COM and inflammatory pathologies such as
      sinusitis.

PMID- 29072241
TI  - Oxidative stress markers and genetic polymorphisms of glutathione S-transferase
      T1, M1, and P1 in a subset of children with autism spectrum disorder in Lagos,
      Nigeria.
AB  - BACKGROUND: The role of oxidative stress has been identified in the development
      of autism spectrum disorder (ASD), and polymorphisms of glutathione S-transferase
      have been associated with some diseases linked to oxidative stress. Hence, we
      evaluated the serum levels of oxidative stress markers and investigated genetic
      polymorphisms of glutathione S-transferase associated with autism. MATERIALS AND
      METHODS: Forty-two children clinically diagnosed with ASD using the Diagnostic
      and Statistical Manual for Mental Disorders (DSM-5) criteria and a clinical
      interview were included in the study. Twenty-three age-matched controls without
      any known genetic/developmental disorder were also recruited. Oxidative stress
      markers along with the genetic polymorphisms of glutathione S-transferase were
      determined. RESULTS: Reduced glutathione in ASD patients was significantly lower
      than the control (P = 0.008), whereas other oxidative stress markers measured
      were not significantly different in both the control and case populations. The
      frequencies of GSTT1 and GSTM1 null genotypes were lower among the controls
      compared with the cases, however, no association risk was observed. The observed
      risk of carrying Val/Val genotype among the cases was approximately six times
      that of the controls. CONCLUSION: Individuals with ASD showed a significant
      diminished level of reduced glutathione, however, the distribution of GSTT1,
      GSTM1, and GSTP1 polymorphisms was not found to be associated with autism in this
      study population.

PMID- 29072242
TI  - Comparison of the EndoVac system and conventional needle irrigation on removal of
      the smear layer in primary molar root canals.
AB  - OBJECTIVE: This study aimed to compare the EndoVac system and conventional needle
      irrigation in removing smear layer (SR) from primary molar root canals. MATERIALS
      AND METHODS: Fifty extracted human primary second molar roots were instrumented
      up to an apical size of 0.04/35 and randomly divided into two main groups; Group
      1: EndoVac system (n = 25) and Group 2: Conventional needle irrigation (n = 25)
      and three subgroups (a) NaOCl + ethylenediaminetetraacetic acid (EDTA) (n = 20)
      (b) ozonated water (OW) + EDTA (n = 20) and (c) saline (control, n = 10). After a
      standardized final irrigation protocol performed for all teeth, scanning electron
      microscope images were taken at *1000 magnification for each thirds of each root
      canal. Data were analyzed by the weighted kappa, Kruskal-Wallis, and Wilcoxon
      signed rank tests. RESULTS: EndoVac was more effective than conventional needle
      in the removal of SR from the apical third of the root canal system (P < 0.05).
      The OW + EDTA regimen provided similar SR removal compared with NaOCl + EDTA.
      CONCLUSIONS: EndoVac has better performance than conventional needle irrigation
      in the removal of the SR in the apical thirds of the primary molar root canals.
      As a final irrigation regimen, the OW + EDTA regimen is as effective as the NaOCl
      + EDTA regimen.

PMID- 29072243
TI  - Evaluation of digital model accuracy and time-dependent deformation of alginate
      impressions.
AB  - OBJECTIVES: The aim of this study was to evaluate the accuracy of digital models
      produced with the three-dimensional dental scanner, and to test the dimensional
      stability of alginate impressions for durations of immediately (T0), 1 day (T1),
      and 2 days (T2). MATERIALS AND METHODS: A total of sixty impressions were taken
      from a master model with an alginate, and were poured into plaster models in
      three different storage periods. Twenty impressions were directly scanned
      (negative digital models), after which plaster models were poured and scanned
      (positive digital models) immediately. The remaining 40 impressions were poured
      after 1 and 2 days. In total, 9 points and 11 linear measurements were used to
      analyze the plaster models, and negative and positive digital models. Time
      dependent deformation of the alginate impressions and the accuracy of the
      conventional plaster models and digital models were evaluated separately.
      RESULTS: Plaster models, negative and positive digital models showed significant
      differences in nearly all measurements at T (0), T (1), and T (2) times (P <
      0.01, P < 0.05, and P < 0.001). Arch perimeter measurements did not differ at T
      (0) and T (1) times (P > 0.05), but they demonstrated statistically significant
      differences at T (2) time (P < 0.05) between the models. CONCLUSIONS: This study
      showed that measurements on negative digital models offer a high degree of
      validity when compared to measurements on positive digital models and plaster
      models; differences between the techniques are clinically acceptable. Direct
      scanning of the impressions is practicable method for orthodontists.

PMID- 29072244
TI  - Oral and dental health in children with chronic liver disease in the Turkey
      Northeast.
AB  - BACKGROUND: It is important to be aware of oral and dental problems in the early
      period in children with chronic liver disease (CLD) to prevent late
      complications. Therefore, we aimed to analyze the oral and dental health status
      in children with CLD. METHODS: The three groups of children (3-18 years old);
      Group 1 (disease group, n = 31) patients with CLD, Group 2 (disease control
      group, n = 17) patients with chronic renal failure, and Group 3 healthy children
      (control group, n = 35). Examination of oral and dental structures were made, and
      then salivary parameters were analyzed. Antegonial index were calculated from
      panoramic X-rays. RESULTS: Enamel hypoplasia was found in 54.8%, 41.1%, and 31.4%
      of the children in the Groups 1, 2, and 3, respectively (P1-3 < 0.05). High
      salivary buffer capacity was found in 45.2% and 70.6% of the patients in Groups 1
      and 2, respectively, and 45.7% of the children in healthy group, (P1-2 and P2-3 <
      0.05). Factors associated with enamel hypoplasia in patients with CLD were male
      gender (64.7% vs. 21.4%, P < 0.05) and the presence of malnutrition (41.1% vs.
      7.1%, P < 0.05). CONCLUSION: Pediatric hepatologists must be aware of the dental
      problems in children with CLD. Enamel hypoplasia is common in children with CLD,
      and it may predispose to dental caries.

PMID- 29072245
TI  - Impact of oral antibiotics on health-related quality of life after mandibular
      third molar surgery: An observational study.
AB  - AIM: To compare the impact of antibiotics on health-related quality of life (QoL)
      outcomes following third molar surgery. MATERIALS AND METHODS: The study
      population consisted of 135 subjects that required surgical extraction of
      mandibular third molar under local anesthesia and met the inclusion criteria. The
      subjects were randomized into three study groups of 45 subjects each: Group A -
      extended amoxicillin/clavulanic acid (GlaxoSmithKline Beecham England), 1 gram
      pre-operatively and then 625 mg BD for 5 days Group B - prophylactic
      amoxicillin/clavulanic acid (GlaxoSmithKline Beecham England) 1 gram pre
      operatively only, and Group C - prophylactic levofloxacin 1 gram pre-operatively
      only. Patients were assessed pre- and post-operatively on days 1, 3, 5, 7, and 14
      using the United Kingdom oral health-related QoL (OHRQoL) questionnaire. RESULTS:
      This study showed that surgical removal of impacted teeth exerted a negative
      influence on patient's QoL across various physical, social, and psychological
      aspects of life. Comparing the three groups, Group A showed a slightly better QoL
      score; although, there was no statistically significant difference among them.
      Studies have shown better clinical recovery following administration of
      antibiotics after third molar surgery. CONCLUSION: There was a significant
      deterioration in OHRQoL in the immediate postoperative period, particularly
      postoperative days 1 and 3 following third molar surgery. QoL was also observed
      to be slightly better in Group A than Groups B and C, although this was not
      statistically significant.

PMID- 29072246
TI  - Changes in periodontal and microbial parameters after the space maintainers
      application.
AB  - AIM: This study aims to evaluate the clinical and microbiological changes
      accompanying the inflammatory process of periodontal tissues during treatment
      with space maintainers (SMs). MATERIALS AND METHODS: The children were separated
      into fixed (Group 1, n = 20) and removable (Group 2, n = 20) appliance groups. A
      full periodontal examination, including probing pocket depth (PPD), bleeding on
      probing (BOP), and plaque index (PI), was performed. Anaerobic microorganisms in
      the crevicular fluid were detected with the culture method. Clinical and
      microbial evaluations were performed before (T0) applications. as well as at
      three (T1), and 9 months intervals (T2) after the application of the fixed or
      removable appliances. RESULTS: The PI, PPD, and BOP scores at the testing sites
      of both groups increased significantly from before treatment (T0) to the 9
      months' time frame (T2) (P < 0.05), The presence of anaerobic bacteria in the
      subgingival dental plaque increased from T0 (n = 13, 65%) to T1 (n = 16, 80%) in
      the fixed SM group, but not statistically significant. The same values were
      obtained in T1 and T2 (n = 16, 80%). CONCLUSION: Although, the results of this
      study demonstrate that the application of fixed or removable SM appliances in
      children induced an increase of clinical periodontal parameters, anaerobic
      microbiota consisting of Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis, and Tannerella forshia were not observed in any of the samples in
      short-term. Further long-term and comprehensive investigations are necessary.

PMID- 29072247
TI  - Effect of saliva decontamination procedures on shear bond strength of a one-step
      adhesive system.
AB  - AIM: To evaluate the effect of different saliva decontamination procedures on the
      shear bond strength of a one-step universal adhesive system (Single BondTM
      Universal Adhesive, 3M ESPE, St. Paul, MN, USA). MATERIALS AND METHODS: The
      occlusal surfaces of 75 human third molars were ground to expose dentin. The
      teeth were divided into the following groups: Group 1 (control group): Single
      BondTM Universal Adhesive was applied to the prepared tooth according to the
      manufacturer's recommendations and light cured; no contamination procedure was
      performed. Group 2: Bonding, light curing, saliva contamination, and dry. Group
      3: Bonding, light curing, saliva contamination, rinse, and dry. Group 4: After
      the procedure performed in Group 2, reapplication of bonding. Group 5: After the
      procedure performed in Group 3, reapplication of bonding. Then, composite resins
      were applied with cylindrical-shaped plastic matrixes and light cured. For shear
      bond testing, a notch-shaped force transducer apparatus was applied to each
      specimen at the interface between the tooth and composite until failure occurred.
      The data were statistically analyzed using one-way ANOVA. RESULTS: One-way ANOVA
      revealed significant differences in shear bond strength between the control group
      and experimental Groups 2 and 4 (P < 0.05). No significant difference was found
      for experimental Groups 3 and 5 when compared to the control group (P > 0.05).
      CONCLUSION: The present in vitro study showed that water rinsing is necessary if
      cured adhesive resin is contaminated with saliva to ensure adequate bond
      strength.

PMID- 29072248
TI  - Torsion of the spermatic cord: An exemplary early presentation.
AB  - Torsion of the spermatic cord may lead to loss of the testis when presentation is
      delayed. In our environment, a high premium is placed on the male child and his
      ability to procreate. Hence, torsion of the spermatic cord is a true surgical
      emergency. Here, we report a case of torsion of the spermatic cord in a 19-year
      old student that exemplifies early presentation and short presentation-detorsion
      time. Immediately after the operation, the clinical information in the patient's
      case file was summarized. A literature search was conducted on the subject
      matter, and the findings were compared with those of the present patient. The
      determinants of outcome include presentation time and the time between
      presentation and operation. Unfortunately, in many series, late presentation is
      still the norm. In the index patient, the presentation time was very short. In
      our environment, patients with torsion of the spermatic cord can present early
      and be operated promptly if we can provide public health education, mobile
      phones, commercial taxis, and good road networks.

PMID- 29072249
TI  - Impalement injury to the abdomen: Report of a case.
AB  - Impalement presents a combination of injuries severe enough to cause the
      homeostatic mechanisms to malfunction or fail. It challenges the abilities of the
      managing team as well as the available medical resources. Its management is even
      more demanding in environments where health-care personnel, facilities for
      emergency care, and communications infrastructure are absent or poorly funded and
      equipped. The primary objective of managing impalement injuries is to prevent
      further injuries and preserve or restore homeostasis. Leaving the impaling object
      in situ until in the operating room is a time proven approach as it allows for
      managing life-threatening hemorrhage in the operating room. Adequate volume
      replacement, good visualization, debridement of injuries, and anti-infective
      measures are complementary. We present a case of type I abdominal impalement in a
      young man who sustained minimal visceral or neurovascular injuries and underwent
      exploratory laparotomy for his injuries; he developed a traumatic incisional
      hernia. He defaulted on the scheduled hernia repair.

PMID- 29072250
TI  - Spontaneous retropharyngeal emphysema: A case report.
AB  - Retropharyngeal emphysema is usually secondary to trauma, iatrogenic injury, and
      obstructive respiratory diseases. Without prompt and adequate treatment, severe
      complication such as airway compromise may occur. Spontaneous retropharyngeal
      emphysema, defined by the presence of free air in the retropharyngeal space
      without any precipitating cause, is a rare clinical condition in pediatric
      otolaryngology. The predominant symptoms are sore throat, odynophagia, dysphagia,
      and neck pain. Here, we report a case of spontaneous retropharyngeal emphysema.

PMID- 29072251
TI  - Conservative surgical treatment of the jaw cysts in children: Case study of five
      patients.
AB  - AIMS: Conservative treatment of jaw cysts establishes low surgical complication
      risk and protects vital anatomical structures such as inferior alveolar nerve,
      maxillary sinus and permanent tooth germs. Marsupialization and decompression
      have been widely used in children. The aim of this study was to evaluate the
      results of the conservative treatment of jaw cysts in five children. MATERIALS
      AND METHODS: This article presents case series of marsupialization in jaw cysts
      associated with impacted teeth in five children. A total of nine impacted teeth
      within the cystic lesions were observed. RESULTS: Complete resolution of all
      cystic lesions and simultaneous eruption of six impacted teeth within the cyst
      were managed. The other two teeth were erupted orthodontically and one had to be
      extracted. CONCLUSIONS: Marsupialization is effective for the treatment of cystic
      lesions in growing patients as it preserves vital anatomical structures and
      enables eruption of the impacted teeth within the cyst.

PMID- 29072253
TI  - Corrigendum: MUS81 nuclease activity is essential for replication stress
      tolerance and chromosome segregation in BRCA2-deficient cells.
AB  - This corrects the article DOI: 10.1038/ncomms15983.

PMID- 29072254
TI  - Acute coronary syndromes: Myocardial salvage with HDL infusion after infarction.

PMID- 29072255
TI  - Anticoagulant therapy: Interaction between NOACs and other drugs increases
      bleeding risk.

PMID- 29072256
TI  - Rapamycin inhibits ox-LDL-induced inflammation in human endothelial cells in
      vitro by inhibiting the mTORC2/PKC/c-Fos pathway.
AB  - Rapamycin and its derivative possess anti-atherosclerosis activity, but its
      effects on adhesion molecule expression and macrophage adhesion to endothelial
      cells during atherosclerosis remain unclear. In this study we explored the
      effects of rapamycin on ox-LDL-induced adhesion molecule expression and
      macrophage adhesion to endothelial cells in vitro and the underlying mechanisms.
      Ox-LDL (6-48 MUg/mL) dose-dependently increased the protein levels of two
      adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and E-selectin, in
      human umbilical vein endothelial cells (HUVECs), whereas pretreatment with
      rapamycin (1-10 MUmol/L) dose-dependently inhibited ox-LDL-induced increase in
      the adhesion molecule expression and macrophage adhesion to endothelial cells.
      Knockdown of mTOR or rictor, rather than raptor, mimicked the effects of
      rapamycin. Ox-LDL (100 MUg/mL) time-dependently increased PKC phosphorylation in
      HUVECs, which was abolished by rapamycin or rictor siRNA. Pretreatment with PKC
      inhibitor staurosporine significantly reduced ox-LDL-stimulated adhesion molecule
      expression and macrophage adhesion to endothelial cells, whereas pretreatment
      with PKC activator PMA/TPA attenuated the inhibitory effect of rapamycin on
      adhesion molecule expression. Ox-LDL (100 MUg/mL) time-dependently increased c
      Fos levels in HUVECs, and pretreatment with rapamycin or rictor siRNA
      significantly decreased expression of c-Fos. Knockdown of c-Fos antagonized ox
      LDL-induced adhesion molecule expression and macrophage adhesion to endothelial
      cells. Our results demonstrate that rapamycin reduces ox-LDL-stimulated adhesion
      molecule expression and macrophage adhesion to endothelial cells by inhibiting
      mTORC2, but not mTORC1, and mTORC2 acts through the PKC/c-Fos signaling pathway.

PMID- 29072258
TI  - A metabolic mechanism analysis of Fuzheng-Huayu formula for improving liver
      cirrhosis with traditional Chinese medicine syndromes.
AB  - Fuzheng-Huayu formula (FZHY), a Chinese herbal mixture prescription, has been
      proven effective in treating liver fibrosis and cirrhosis in both clinical trials
      and animal experiments. In this study we assessed the metabolic mechanisms of
      traditional Chinese medicine (TCM) syndrome-based FZHY treatment in liver
      cirrhosis (LC). A total of 113 participants, including 50 healthy controls and 63
      LC patients, were recruited. According to the diagnosis and differentiation of
      the TCM syndromes, the LC patients were classified into 5 TCM syndrome groups
      including the liver stagnation syndrome (LSS), spleen deficiency and damp
      overabundance syndrome (SDDOS), damp-heat accumulation syndrome (DHAS), liver
      kidney Yin deficiency syndrome (LKYDS), and blood stagnation syndrome (BSS), and
      administered FZHY for 6 months. FZHY treatment significantly decreased serum
      levels of hyaluronic acid (HA), a biochemical marker for LC, as well as TCM
      syndrome scores (the TCM syndrome scores were decreased in all the groups with
      significant decreases in the LSS and LKYDS groups). Furthermore, FZHY treatment
      gradually shifted the metabolic profiles of LC patients from a pathologic state
      to a healthy state, especially in LC patients with LSS and LKYDS. Twenty-two
      differently altered metabolites (DAMs) were identified, including carbohydrates,
      amino acids, fatty acids, etc with 9 DAMs in LSS patients, 9 in LKYDS patients,
      and 4 in other patients. The metabolic pathways involved in the conversion of
      amino acids and the body's detoxification process were regulated first, followed
      by the pathways involved in the body's energy supply process. In conclusion, the
      evaluation of the effect of TCM syndrome-based FZHY treatment show that FZHY has
      a better effect on LKYDS and LSS than on the other TCM syndromes, and the
      metabolic mechanisms might be involved in the increased detoxification function
      in LKYDS and the improvement of energy supply in LSS, which provides important
      evidence for the clinical application of TCM syndrome-based treatment.

PMID- 29072257
TI  - Therapeutic effects of a taurine-magnesium coordination compound on experimental
      models of type 2 short QT syndrome.
AB  - Short QT syndrome (SQTS) is a genetic arrhythmogenic disease that can cause
      malignant arrhythmia and sudden cardiac death. The current therapies for SQTS
      have application restrictions. We previously found that Mg. (NH2CH2CH2SO3)2. H2O,
      a taurine-magnesium coordination compound (TMCC) exerted anti-arrhythmic effects
      with low toxicity. In this study we established 3 different models to assess the
      potential anti-arrhythmic effects of TMCC on type 2 short QT syndrome (SQT2). In
      Langendorff guinea pig-perfused hearts, perfusion of pinacidil (20 MUmol/L)
      significantly shortened the QT interval and QTpeak and increased rTp-Te (P<0.05
      vs control). Subsequently, perfusion of TMCC (1-4 mmol/L) dose-dependently
      increased the QT interval and QTpeak (P<0.01 vs pinacidil). TMCC perfusion also
      reversed the rTp-Te value to the normal range. In guinea pig ventricular
      myocytes, perfusion of trapidil (1 mmol/L) significantly shortened the action
      potential duration at 50% (APD50) and 90% repolarization (APD90), which was
      significantly reversed by TMCC (0.01-1 mmol/L, P<0.05 vs trapidil). In HEK293
      cells that stably expressed the outward delayed rectifier potassium channels
      (IKs), perfusion of TMCC (0.01-1 mmol/L) dose-dependently inhibited the IKs
      current with an IC50 value of 201.1 MUmol/L. The present study provides evidence
      that TMCC can extend the repolarization period and inhibit the repolarizing
      current, IKs, thereby representing a therapeutic candidate for ventricular
      arrhythmia in SQT2.

PMID- 29072260
TI  - Nicolaas Bloembergen (1920-2017).

PMID- 29072259
TI  - Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated
      ion channels.
AB  - Barbaloin (10-beta-D-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)
      anthracenone) is extracted from the aloe plant and has been reported to have anti
      inflammatory, antitumor, antibacterial, and other biological activities. Here, we
      investigated the effects of barbaloin on cardiac electrophysiology, which has not
      been reported thus far. Cardiac action potentials (APs) and ionic currents were
      recorded in isolated rabbit ventricular myocytes using whole-cell patch-clamp
      technique. Additionally, the antiarrhythmic effect of barbaloin was examined in
      Langendorff-perfused rabbit hearts. In current-clamp recording, application of
      barbaloin (100 and 200 MUmol/L) dose-dependently reduced the action potential
      duration (APD) and the maximum depolarization velocity (Vmax), and attenuated APD
      reverse-rate dependence (RRD) in ventricular myocytes. Furthermore, barbaloin
      (100 and 200 MUmol/L) effectively eliminated ATX II-induced early
      afterdepolarizations (EADs) and Ca2+-induced delayed afterdepolarizations (DADs)
      in ventricular myocytes. In voltage-clamp recording, barbaloin (10-200 MUmol/L)
      dose-dependently inhibited L-type calcium current (ICa.L) and peak sodium current
      (INa.P) with IC50 values of 137.06 and 559.80 MUmol/L, respectively. Application
      of barbaloin (100, 200 MUmol/L) decreased ATX II-enhanced late sodium current
      (INa.L) by 36.6%+/-3.3% and 71.8%+/-6.5%, respectively. However, barbaloin up to
      800 MUmol/L did not affect the inward rectifier potassium current (IK1) or the
      rapidly activated delayed rectifier potassium current (IKr) in ventricular
      myocytes. In Langendorff-perfused rabbit hearts, barbaloin (200 MUmol/L)
      significantly inhibited aconitine-induced ventricular arrhythmias. These results
      demonstrate that barbaloin has potential as an antiarrhythmic drug.

PMID- 29072262
TI  - Materials science: Atomistic views of deformation.

PMID- 29072261
TI  - In situ X-ray diffraction measurement of shock-wave-driven twinning and lattice
      dynamics.
AB  - Pressure-driven shock waves in solid materials can cause extreme damage and
      deformation. Understanding this deformation and the associated defects that are
      created in the material is crucial in the study of a wide range of phenomena,
      including planetary formation and asteroid impact sites, the formation of
      interstellar dust clouds, ballistic penetrators, spacecraft shielding and
      ductility in high-performance ceramics. At the lattice level, the basic
      mechanisms of plastic deformation are twinning (whereby crystallites with a
      mirror-image lattice form) and slip (whereby lattice dislocations are generated
      and move), but determining which of these mechanisms is active during deformation
      is challenging. Experiments that characterized lattice defects have typically
      examined the microstructure of samples after deformation, and so are complicated
      by post-shock annealing and reverberations. In addition, measurements have been
      limited to relatively modest pressures (less than 100 gigapascals). In situ X-ray
      diffraction experiments can provide insights into the dynamic behaviour of
      materials, but have only recently been applied to plasticity during shock
      compression and have yet to provide detailed insight into competing deformation
      mechanisms. Here we present X-ray diffraction experiments with femtosecond
      resolution that capture in situ, lattice-level information on the microstructural
      processes that drive shock-wave-driven deformation. To demonstrate this method we
      shock-compress the body-centred-cubic material tantalum-an important material for
      high-energy-density physics owing to its high shock impedance and high X-ray
      opacity. Tantalum is also a material for which previous shock compression
      simulations and experiments have provided conflicting information about the
      dominant deformation mechanism. Our experiments reveal twinning and related
      lattice rotation occurring on the timescale of tens of picoseconds. In addition,
      despite the common association between twinning and strong shocks, we find a
      transition from twinning to dislocation-slip-dominated plasticity at high
      pressure (more than 150 gigapascals), a regime that recovery experiments cannot
      accurately access. The techniques demonstrated here will be useful for studying
      shock waves and other high-strain-rate phenomena, as well as a broad range of
      processes induced by plasticity.

PMID- 29072263
TI  - Public engagement: Young scientists welcome at IPBES.

PMID- 29072266
TI  - Evolution: Fan-assisted insects.

PMID- 29072267
TI  - Science writing: On what's neither clear nor obvious.

PMID- 29072268
TI  - Construction: limit China's sand mining.

PMID- 29072270
TI  - Biophysics: Rapid mass changes measured in cells.

PMID- 29072272
TI  - Construction: use waste for building.

PMID- 29072271
TI  - Inertial picobalance reveals fast mass fluctuations in mammalian cells.
AB  - The regulation of size, volume and mass in living cells is physiologically
      important, and dysregulation of these parameters gives rise to many diseases.
      Cell mass is largely determined by the amount of water, proteins, lipids,
      carbohydrates and nucleic acids present in a cell, and is tightly linked to
      metabolism, proliferation and gene expression. Technologies have emerged in
      recent years that make it possible to track the masses of single suspended cells
      and adherent cells. However, it has not been possible to track individual
      adherent cells in physiological conditions at the mass and time resolutions
      required to observe fast cellular dynamics. Here we introduce a cell balance (a
      'picobalance'), based on an optically excited microresonator, that measures the
      total mass of single or multiple adherent cells in culture conditions over days
      with millisecond time resolution and picogram mass sensitivity. Using our
      technique, we observe that the mass of living mammalian cells fluctuates
      intrinsically by around one to four per cent over timescales of seconds
      throughout the cell cycle. Perturbation experiments link these mass fluctuations
      to the basic cellular processes of ATP synthesis and water transport.
      Furthermore, we show that growth and cell cycle progression are arrested in cells
      infected with vaccinia virus, but mass fluctuations continue until cell death.
      Our measurements suggest that all living cells show fast and subtle mass
      fluctuations throughout the cell cycle. As our cell balance is easy to handle and
      compatible with fluorescence microscopy, we anticipate that our approach will
      contribute to the understanding of cell mass regulation in various cell states
      and across timescales, which is important in areas including physiology, cancer
      research, stem-cell differentiation and drug discovery.

PMID- 29072273
TI  - Poaching: Is snow leopard tally underestimated?

PMID- 29072274
TI  - Evidence of marine ice-cliff instability in Pine Island Bay from iceberg-keel
      plough marks.
AB  - Marine ice-cliff instability (MICI) processes could accelerate future retreat of
      the Antarctic Ice Sheet if ice shelves that buttress grounding lines more than
      800 metres below sea level are lost. The present-day grounding zones of the Pine
      Island and Thwaites glaciers in West Antarctica need to retreat only short
      distances before they reach extensive retrograde slopes. When grounding zones of
      glaciers retreat onto such slopes, theoretical considerations and modelling
      results indicate that the retreat becomes unstable (marine ice-sheet instability)
      and thus accelerates. It is thought that MICI is triggered when this retreat
      produces ice cliffs above the water line with heights approaching about 90
      metres. However, observational evidence confirming the action of MICI has not
      previously been reported. Here we present observational evidence that rapid
      deglacial ice-sheet retreat into Pine Island Bay proceeded in a similar manner to
      that simulated in a recent modelling study, driven by MICI. Iceberg-keel plough
      marks on the sea-floor provide geological evidence of past and present iceberg
      morphology, keel depth and drift direction. From the planform shape and cross
      sectional morphologies of iceberg-keel plough marks, we find that iceberg calving
      during the most recent deglaciation was not characterized by small numbers of
      large, tabular icebergs as is observed today, which would produce wide, flat
      based plough marks or toothcomb-like multi-keeled plough marks. Instead, it was
      characterized by large numbers of smaller icebergs with V-shaped keels.
      Geological evidence of the form and water-depth distribution of the plough marks
      indicates calving-margin thicknesses equivalent to the threshold that is
      predicted to trigger ice-cliff structural collapse as a result of MICI. We infer
      rapid and sustained ice-sheet retreat driven by MICI, commencing around 12,300
      years ago and terminating before about 11,200 years ago, which produced large
      numbers of icebergs smaller than the typical tabular icebergs produced today. Our
      findings demonstrate the effective operation of MICI in the past, and highlight
      its potential contribution to accelerated future retreat of the Antarctic Ice
      Sheet.

PMID- 29072276
TI  - In Retrospect: Twenty years of drying droplets.

PMID- 29072278
TI  - Corrections.

PMID- 29072277
TI  - Many junior scientists need to take a hard look at their job prospects.

PMID- 29072279
TI  - CRISPR hacks enable pinpoint repairs to genome.

PMID- 29072281
TI  - India gears up for second Moon mission.

PMID- 29072280
TI  - Data science can improve aid distribution.

PMID- 29072282
TI  - Jupiter's stormy winds churn deep into the planet.

PMID- 29072284
TI  - Reclassify waste to shift the nuclear landscape.

PMID- 29072283
TI  - To stay young, kill zombie cells.

PMID- 29072285
TI  - Cancer biology still needs physicists.

PMID- 29072287
TI  - Photons pair up like superconducting electrons.

PMID- 29072286
TI  - Sleeping sickness can now be cured with pills.

PMID- 29072288
TI  - A death sentence, Hawking's thesis and China's ambitions.

PMID- 29072289
TI  - The Human Cell Atlas: from vision to reality.

PMID- 29072290
TI  - Out of the Syrian crisis, a data revolution takes shape.

PMID- 29072291
TI  - Efforts to save leading Hungarian university hit hurdle.

PMID- 29072293
TI  - Single-cell transcriptomics reconstructs fate conversion from fibroblast to
      cardiomyocyte.
AB  - Direct lineage conversion offers a new strategy for tissue regeneration and
      disease modelling. Despite recent success in directly reprogramming fibroblasts
      into various cell types, the precise changes that occur as fibroblasts
      progressively convert to the target cell fates remain unclear. The inherent
      heterogeneity and asynchronous nature of the reprogramming process renders it
      difficult to study this process using bulk genomic techniques. Here we used
      single-cell RNA sequencing to overcome this limitation and analysed global
      transcriptome changes at early stages during the reprogramming of mouse
      fibroblasts into induced cardiomyocytes (iCMs). Using unsupervised dimensionality
      reduction and clustering algorithms, we identified molecularly distinct
      subpopulations of cells during reprogramming. We also constructed routes of iCM
      formation, and delineated the relationship between cell proliferation and iCM
      induction. Further analysis of global gene expression changes during
      reprogramming revealed unexpected downregulation of factors involved in mRNA
      processing and splicing. Detailed functional analysis of the top candidate
      splicing factor, Ptbp1, revealed that it is a critical barrier for the
      acquisition of cardiomyocyte-specific splicing patterns in fibroblasts.
      Concomitantly, Ptbp1 depletion promoted cardiac transcriptome acquisition and
      increased iCM reprogramming efficiency. Additional quantitative analysis of our
      dataset revealed a strong correlation between the expression of each
      reprogramming factor and the progress of individual cells through the
      reprogramming process, and led to the discovery of new surface markers for the
      enrichment of iCMs. In summary, our single-cell transcriptomics approaches
      enabled us to reconstruct the reprogramming trajectory and to uncover
      intermediate cell populations, gene pathways and regulators involved in iCM
      induction.

PMID- 29072294
TI  - Reductions in global biodiversity loss predicted from conservation spending.
AB  - Halting global biodiversity loss is central to the Convention on Biological
      Diversity and United Nations Sustainable Development Goals, but success to date
      has been very limited. A critical determinant of success in achieving these goals
      is the financing that is committed to maintaining biodiversity; however,
      financing decisions are hindered by considerable uncertainty over the likely
      impact of any conservation investment. For greater effectiveness, we need an
      evidence-based model that shows how conservation spending quantitatively reduces
      the rate of biodiversity loss. Here we demonstrate such a model, and empirically
      quantify how conservation investment reduced biodiversity loss in 109 countries
      (signatories to the Convention on Biological Diversity and Sustainable
      Development Goals), by a median average of 29% per country between 1996 and 2008.
      We also show that biodiversity changes in signatory countries can be predicted
      with high accuracy, using a dual model that balances the effects of conservation
      investment against those of economic, agricultural and population growth (human
      development pressures). Decision-makers can use this model to forecast the
      improvement that any proposed biodiversity budget would achieve under various
      scenarios of human development pressure, and then compare these forecasts to any
      chosen policy target. We find that the impact of spending decreases as human
      development pressures grow, which implies that funding may need to increase over
      time. The model offers a flexible tool for balancing the Sustainable Development
      Goals of human development and maintaining biodiversity, by predicting the
      dynamic changes in conservation finance that will be needed as human development
      proceeds.

PMID- 29072292
TI  - IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral
      activity.
AB  - Interleukin-1 receptor 8 (IL-1R8, also known as single immunoglobulin IL-1R
      related receptor, SIGIRR, or TIR8) is a member of the IL-1 receptor (ILR) family
      with distinct structural and functional characteristics, acting as a negative
      regulator of ILR and Toll-like receptor (TLR) downstream signalling pathways and
      inflammation. Natural killer (NK) cells are innate lymphoid cells which mediate
      resistance against pathogens and contribute to the activation and orientation of
      adaptive immune responses. NK cells mediate resistance against haematopoietic
      neoplasms but are generally considered to play a minor role in solid tumour
      carcinogenesis. Here we report that IL-1R8 serves as a checkpoint for NK cell
      maturation and effector function. Its genetic blockade unleashes NK-cell-mediated
      resistance to hepatic carcinogenesis, haematogenous liver and lung metastasis,
      and cytomegalovirus infection.

PMID- 29072295
TI  - Microbiology: Bacteria disarm host-defence proteins.

PMID- 29072296
TI  - Embryonic epigenetic reprogramming by a pioneer transcription factor in plants.
AB  - Epigenetic modifications, including chromatin modifications and DNA methylation,
      have a central role in the regulation of gene expression in plants and animals.
      The transmission of epigenetic marks is crucial for certain genes to retain cell
      lineage-specific expression patterns and maintain cell fate. However, the marks
      that have accumulated at regulatory loci during growth and development or in
      response to environmental stimuli need to be deleted in gametes or embryos,
      particularly in organisms such as plants that do not set aside a germ line, to
      ensure the proper development of offspring. In Arabidopsis thaliana, prolonged
      exposure to cold temperatures (winter cold), in a process known as vernalization,
      triggers the mitotically stable epigenetic silencing of the potent floral
      repressor FLOWERING LOCUS C (FLC), and renders plants competent to flower in the
      spring; however, this silencing is reset during each generation. Here we show
      that the seed-specific transcription factor LEAFY COTYLEDON1 (LEC1) promotes the
      initial establishment of an active chromatin state at FLC and activates its
      expression de novo in the pro-embryo, thus reversing the silenced state inherited
      from gametes. This active chromatin state is passed on from the pro-embryo to
      post-embryonic life, and leads to transmission of the embryonic memory of FLC
      activation to post-embryonic stages. Our findings reveal a mechanism for the
      reprogramming of embryonic chromatin states in plants, and provide insights into
      the epigenetic memory of embryonic active gene expression in post-embryonic
      phases, through which an embryonic factor acts to 'control' post-embryonic
      development processes that are distinct from embryogenesis in plants.

PMID- 29072298
TI  - Ecology: The effect of conservation spending.

PMID- 29072297
TI  - The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution.
AB  - Modifications on mRNA offer the potential of regulating mRNA fate post
      transcriptionally. Recent studies suggested the widespread presence of N1
      methyladenosine (m1A), which disrupts Watson-Crick base pairing, at internal
      sites of mRNAs. These studies lacked the resolution of identifying individual
      modified bases, and did not identify specific sequence motifs undergoing the
      modification or an enzymatic machinery catalysing them, rendering it challenging
      to validate and functionally characterize putative sites. Here we develop an
      approach that allows the transcriptome-wide mapping of m1A at single-nucleotide
      resolution. Within the cytosol, m1A is present in a low number of mRNAs,
      typically at low stoichiometries, and almost invariably in tRNA T-loop-like
      structures, where it is introduced by the TRMT6/TRMT61A complex. We identify a
      single m1A site in the mitochondrial ND5 mRNA, catalysed by TRMT10C, with
      methylation levels that are highly tissue specific and tightly developmentally
      controlled. m1A leads to translational repression, probably through a mechanism
      involving ribosomal scanning or translation. Our findings suggest that m1A on
      mRNA, probably because of its disruptive impact on base pairing, leads to
      translational repression, and is generally avoided by cells, while revealing one
      case in mitochondria where tight spatiotemporal control over m1A levels was
      adopted as a potential means of post-transcriptional regulation.

PMID- 29072301
TI  - Epitranscriptomics: Shrinking maps of RNA modifications.

PMID- 29072300
TI  - A global resource allocation strategy governs growth transition kinetics of
      Escherichia coli.
AB  - A grand challenge of systems biology is to predict the kinetic responses of
      living systems to perturbations starting from the underlying molecular
      interactions. Changes in the nutrient environment have long been used to study
      regulation and adaptation phenomena in microorganisms and they remain a topic of
      active investigation. Although much is known about the molecular interactions
      that govern the regulation of key metabolic processes in response to applied
      perturbations, they are insufficiently quantified for predictive bottom-up
      modelling. Here we develop a top-down approach, expanding the recently
      established coarse-grained proteome allocation models from steady-state growth
      into the kinetic regime. Using only qualitative knowledge of the underlying
      regulatory processes and imposing the condition of flux balance, we derive a
      quantitative model of bacterial growth transitions that is independent of
      inaccessible kinetic parameters. The resulting flux-controlled regulation model
      accurately predicts the time course of gene expression and biomass accumulation
      in response to carbon upshifts and downshifts (for example, diauxic shifts)
      without adjustable parameters. As predicted by the model and validated by
      quantitative proteomics, cells exhibit suboptimal recovery kinetics in response
      to nutrient shifts owing to a rigid strategy of protein synthesis allocation,
      which is not directed towards alleviating specific metabolic bottlenecks. Our
      approach does not rely on kinetic parameters, and therefore points to a
      theoretical framework for describing a broad range of such kinetic processes
      without detailed knowledge of the underlying biochemical reactions.

PMID- 29072299
TI  - Reversing SKI-SMAD4-mediated suppression is essential for TH17 cell
      differentiation.
AB  - T helper 17 (TH17) cells are critically involved in host defence, inflammation,
      and autoimmunity. Transforming growth factor beta (TGFbeta) is instrumental in
      TH17 cell differentiation by cooperating with interleukin-6 (refs 6, 7). Yet, the
      mechanism by which TGFbeta enables TH17 cell differentiation remains elusive.
      Here we reveal that TGFbeta enables TH17 cell differentiation by reversing SKI
      SMAD4-mediated suppression of the expression of the retinoic acid receptor (RAR)
      related orphan receptor gammat (RORgammat). We found that, unlike wild-type T
      cells, SMAD4-deficient T cells differentiate into TH17 cells in the absence of
      TGFbeta signalling in a RORgammat-dependent manner. Ectopic SMAD4 expression
      suppresses RORgammat expression and TH17 cell differentiation of SMAD4-deficient
      T cells. However, TGFbeta neutralizes SMAD4-mediated suppression without
      affecting SMAD4 binding to the Rorc locus. Proteomic analysis revealed that SMAD4
      interacts with SKI, a transcriptional repressor that is degraded upon TGFbeta
      stimulation. SKI controls histone acetylation and deacetylation of the Rorc locus
      and TH17 cell differentiation via SMAD4: ectopic SKI expression inhibits H3K9
      acetylation of the Rorc locus, Rorc expression, and TH17 cell differentiation in
      a SMAD4-dependent manner. Therefore, TGFbeta-induced disruption of SKI reverses
      SKI-SMAD4-mediated suppression of RORgammat to enable TH17 cell differentiation.
      This study reveals a critical mechanism by which TGFbeta controls TH17 cell
      differentiation and uncovers the SKI-SMAD4 axis as a potential therapeutic target
      for treating TH17-related diseases.

PMID- 29072303
TI  - Impact of age on cardiovascular function, inflammation, and oxidative stress in
      experimental asphyxial cardiac arrest.
AB  - BACKGROUND: Advanced age is an independent predictor of poor outcome after
      cardiac arrest (CA). From experimental studies of regional ischemia-reperfusion
      injury, advanced age is associated with larger infarct size, reduced organ
      function, and augmented oxidative stress. The objective of this study was to
      investigate the effect of age on cardiovascular function, oxidative stress,
      inflammation, and endothelial activation after CA representing global ischemia
      reperfusion. METHODS: Aged (26 months) and young (5 months) rats were subjected
      to 8 min of asphyxia induced CA, resuscitated and observed for 360 min. Left
      ventricular pressure-derived cardiac function was measured at baseline and 360
      min after CA. Blood samples obtained at baseline, 120 min, and 360 min after CA
      were analyzed for IL-1beta, IL-6, IL-10, TNF-alpha, elastase, sE-selectin, sL
      selectin, sI-CAM1, hemeoxygenase-1 (HO-1) and protein carbonyl. Tissue samples of
      brain, heart, kidney, and lung were analyzed for HO-1. RESULTS: Cardiac function,
      evaluated by dP/dtmax and dP/dtmin , was decreased after CA in both young and
      aged rats, with no group differences. Mean arterial pressure increased after CA
      in young, but not old rats. Aged rats showed significantly higher plasma levels
      of elastase and sE-selectin after CA, and there was a significant different
      development over time between groups for IL-6 and IL-10. Young rats showed higher
      levels of HO-1 in plasma and renal tissue after CA. CONCLUSION: In a rat model of
      asphyxial CA, advanced age is associated with an attenuated hyperdynamic blood
      pressure response and increased endothelial activation.

PMID- 29072304
TI  - Secular trends are associated with the demographic and epidemiologic transitions
      in an indigenous community in Oaxaca, Southern Mexico.
AB  - OBJECTIVE: To test the hypothesis that secular changes in body size and age at
      menarche are related to the demographic and epidemiologic transitions in an
      indigenous community in Oaxaca, southern Mexico. METHODS: Data were derived from
      surveys of a Zapotec-speaking community conducted between 1968 and 2000.
      Segmented linear regressions of height, weight, BMI and recalled age at menarche
      on year of birth in cohorts of adults born before and after the demographic
      transition were used to evaluate secular changes. Corresponding comparisons of
      body size (MANCOVA controlling for age) and age at menarche (status quo, probit
      analysis) were done for samples of children and adolescents born before and after
      the epidemiological transition. RESULTS: Height and weight increased in adults
      born after the demographic transition (mid-1950s), and especially in children and
      adolescents born after the epidemiological transition (mid-1980s). Age at
      menarche also decreased significantly in women born after the demographic
      transition, but at a more rapid estimated rate in adolescents born after the
      epidemiological transition. Secular gains in body weight were proportional to
      those for height among children and adolescents, but adults, males more so than
      females, gained proportionally more weight. CONCLUSIONS: The secular trend in
      height in adults of both sexes was associated with the decade of the demographic
      transition in the mid-1950s. Significant secular gains in size attained and age
      at menarche occurred in children and youth born after the epidemiologic
      transition which likely reflected improved health and nutritional conditions
      since the mid-1980s.

PMID- 29072305
TI  - Life History theory hypotheses on child growth: Potential implications for short
      and long-term child growth, development and health.
AB  - Life history theory integrates ecological, physiological, and molecular layers
      within an evolutionary framework to understand organisms' strategies to optimize
      survival and reproduction. Two life history hypotheses and their implications for
      child growth, development, and health (illustrated in the South African context)
      are reviewed here. One hypothesis suggests that there is an energy trade-off
      between linear growth and brain growth. Undernutrition in infancy and childhood
      may trigger adaptive physiological mechanisms prioritizing the brain at the
      expense of body growth. Another hypothesis is that the period from conception to
      infancy is a critical window of developmental plasticity of linear growth, the
      duration of which may vary between and within populations. The transition from
      infancy to childhood may mark the end of a critical window of opportunity for
      improving child growth. Both hypotheses emphasize the developmental plasticity of
      linear growth and the potential determinants of growth variability (including the
      role of parent-offspring conflict in maternal resources allocation). Implications
      of these hypotheses in populations with high burdens of undernutrition and
      infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated
      with adverse birth outcomes, short duration of breastfeeding, and social
      consequences) may lead to a shortened window of developmental plasticity of
      growth. Furthermore, undernutrition and infectious diseases in children living in
      South Africa, a country undergoing a rapid nutrition transition, may have adverse
      consequences on individuals' cognitive abilities and risks of cardio-metabolic
      diseases. Studies are needed to identify physiological mechanisms underlying
      energy allocation between biological functions and their potential impacts on
      health.

PMID- 29072306
TI  - Attitudes of physicians towards the care of critically ill elderly patients - a
      European survey.
AB  - BACKGROUND: Very elderly patients are one of the fastest growing population in
      ICUs worldwide. There are lots of controversies regarding admission, discharge of
      critically ill elderly patients, and also on treatment intensity during the ICU
      stay. As a consequence, practices vary considerably from one ICU to another. In
      that perspective, we collected opinions of experienced ICU physicians across
      Europe on statements focusing on patients older than 80. METHODS: We sent an
      online questionnaire to the coordinator ICU physician of all participating ICUs
      of an recent European, observational study of Very old critically Ill Patients
      (VIP1 study). This questionnaire contained 12 statements about admission, triage,
      treatment and discharge of patients older than 80. RESULTS: We received answers
      from 162 ICUs (52% of VIP1-study) spanning 20 different European countries. There
      were major disagreements between ICUs. Responders disagree that: there is clear
      evidence that ICU admission is beneficial (37%); seeking relatives' opinion is
      mandatory (17%); written triage guidelines must be available either at the
      hospital or ICU level (20%); level of care should be reduced (25%); a
      consultation of a geriatrician should be sought (34%) and a geriatrician should
      be part of the post-ICU trail (11%). The percentage of disagreement varies
      between statements and European regions. CONCLUSION: There are major differences
      in the attitude of European ICU physicians on the admission, triage and treatment
      policies of patients older than 80 emphasizing the lack of consensus and poor
      level of evidence for most of the statements and outlining the need for future
      interventional studies.

PMID- 29072307
TI  - Testing inter-observer reliability of the Transition Analysis aging method on the
      William M. Bass forensic skeletal collection.
AB  - OBJECTIVES: Skeletal age estimation is an integral part of the biological
      profile. Recent work shows how multiple-trait approaches better capture
      senescence as it occurs at different rates among individuals. Furthermore, a
      Bayesian statistical framework of analysis provides more useful age estimates.
      The component-scoring method of Transition Analysis (TA) may resolve many of the
      functional and statistical limitations of traditional phase-aging methods and is
      applicable to both paleodemography and forensic casework. The present study
      contributes to TA-research by validating TA for multiple, differently experienced
      observers using a collection of modern forensic skeletal cases. MATERIALS AND
      METHODS: Five researchers independently applied TA to a random sample of 58
      documented individuals from the William M. Bass Forensic Skeletal Collection, for
      whom knowledge of chronological age was withheld. Resulting scores were input
      into the ADBOU software and maximum likelihood estimates (MLEs) and 95%
      confidence intervals (CIs) were produced using the forensic prior. Krippendorff's
      alpha was used to evaluate interrater reliability and agreement. Inaccuracy and
      bias were measured to gauge the magnitude and direction of difference between
      estimated ages and chronological ages among the five observers. RESULTS: The
      majority of traits had moderate to excellent agreement among observers (>=0.6).
      The superior surface morphology had the least congruence (0.4), while the ventral
      symphyseal margin had the most (0.9) among scores. Inaccuracy was the lowest for
      individuals younger than 30 and the greatest for individuals over 60. Consistent
      over-estimation of individuals younger than 30 and under-estimation of
      individuals over 40 years old occurred. Individuals in their 30s showed a mixed
      pattern of under- and over-estimation among observers. DISCUSSION: These results
      support the use of the TA method by researchers of varying experience levels.
      Further, they validate its use on forensic cases, given the low error overall.

PMID- 29072302
TI  - Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer with
      neuroendocrine features. MCC pathogenesis is associated with either the presence
      of Merkel cell polyomavirus or chronic exposure to ultraviolet light (UV), which
      can cause a characteristic pattern of multiple DNA mutations. Notably, in the
      Northern hemisphere, the majority of MCC cases are of viral aetiology; by
      contrast, in areas with high UV exposure, UV-mediated carcinogenesis is
      predominant. The two aetiologies share similar clinical, histopathological and
      prognostic characteristics. MCC presents with a solitary cutaneous or
      subcutaneous nodule, most frequently in sun-exposed areas. In fact, UV exposure
      is probably involved in both viral-mediated and non-viral-mediated
      carcinogenesis, by contributing to immunosuppression or DNA damage, respectively.
      Confirmation of diagnosis relies on analyses of histological features and
      immunological marker expression profiles of the lesion. At primary diagnosis,
      loco-regional metastases are already present in ~30% of patients. Excision of the
      tumour is the first-line therapy; if not feasible, radiotherapy can often
      effectively control the disease. Chemotherapy was the only alternative in
      advanced-stage or refractory MCC until several clinical trials demonstrated the
      efficacy of immune-checkpoint inhibitors.

PMID- 29072309
TI  - HLA-Cw6 and psoriasis.
AB  - Psoriasis is a multifactorial disease with a strong genetic background. HLA-Cw6
      is one of the most strongly associated psoriasis susceptibility alleles. It is
      repeatedly observed to affect disease course, phenotypic features, severity,
      comorbidities and treatment outcomes. To the best of our knowledge, the roles of
      HLA-Cw6 in psoriasis have not yet been thoroughly reviewed. The worldwide
      frequency of the HLA-Cw6 allele varies greatly, with it being generally higher in
      white people than in Asians. The allele is associated with type I early-onset
      psoriasis. Stress, obesity and streptococcal pharyngitis are commonly observed in
      HLA-Cw6-positive patients. Phenotypically, HLA-Cw6 has been found to be
      associated with guttate psoriasis. In addition, patients carrying the allele are
      more likely to have arm, leg and trunk involvement, and the Koebner phenomenon.
      Patients with psoriatic arthritis with HLA-Cw6 more often have early onset and
      tend to show cutaneous symptoms before musculoskeletal symptoms. HLA-Cw6-positive
      patients have been shown in several studies to be more responsive to methotrexate
      and ustekinumab. However, this difference in ustekinumab efficacy was only
      moderate in a post-hoc analysis of a pivotal phase III study. HLA-Cw6 positivity
      also tends to be less frequent in high-need patients who fail conventional
      therapy. Small studies have also investigated the role of HLA-Cw6 in remission of
      psoriasis during pregnancy, and with the comorbidities of photosensitivity and
      atherosclerosis. Given the diverse nature of psoriasis pathogenesis, as well as
      the difference of HLA-Cw6 positivity in different ethnic groups, more studies are
      needed to confirm the role of HLA-Cw6 in psoriasis.

PMID- 29072308
TI  - Technical Note: Evaluation of an iterative reconstruction algorithm for optical
      CT radiation dosimetry.
AB  - PURPOSE: Iterative CT reconstruction algorithms are gaining popularity as GPU
      based computation becomes more accessible. These algorithms are desirable in x
      ray CT for their ability to achieve similar image quality at a fraction of the
      dose required for standard filtered backprojection reconstructions. In optical CT
      dosimetry, the noise reduction capability of such algorithms is similarly
      desirable because noise has a detrimental effect on the precision of dosimetric
      analysis, and can create misleading test results. In this study, we evaluate an
      iterative CT reconstruction algorithm for gel dosimetry, with special attention
      to the challenging dosimetry of small fields. METHODS: An existing ordered
      subsets convex algorithm using total variation minimization regularization (OSC
      TV) was implemented. Three datasets, which represent the extreme cases of gel
      dosimetry, were examined: a large, 15 cm diameter uniform phantom, a 1.35 cm
      diameter finger phantom, and a 15 cm gel dosimeter irradiated with 3 * 3, 2 * 2,
      1 * 1, and 0.6 * 0.6 cm fields. These were scanned on an in-house scanning laser
      system, and reconstructed with both filtered backprojection and OSC-TV with a
      range of regularization constants. The contrast to artifact + noise ratio (CANR)
      and penumbra width measurements (80% to 20% and 95% to 5% distances) were used to
      compare reconstructions. RESULTS: Our results showed that OSC-TV can achieve 3-5*
      improvement in contrast to artifact + noise ratio compared to filtered
      backprojection, while preserving the shape of steep dose gradients. For very
      small objects (<= 0.6 * 0.6 cm fields in a 16 * 16 cm field of view), the mean
      value in the center of the object can be suppressed if the regularization
      constant is improperly set, which must be avoided. CONCLUSIONS: Overall, the
      results indicate that OSC-TV is a suitable reconstruction algorithm for gel
      dosimetry, provided care is taken in setting the regularization parameter when
      reconstructing objects that are small compared to the scanner field of view.

PMID- 29072310
TI  - Infanticide in chimpanzees: Taphonomic case studies from Gombe.
AB  - OBJECTIVES: We present a study of skeletal damage to four chimpanzee (Pan
      troglodytes) infanticide victims from Gombe National Park, Tanzania. Skeletal
      analysis may provide insight into the adaptive significance of infanticide by
      examining whether nutritional benefits sufficiently explain infanticidal
      behavior. The nutritional hypothesis would be supported if bone survivorship
      rates and skeletal damage patterns are comparable to those of monkey prey. If
      not, other explanations, such as the resource competition hypothesis, should be
      considered. METHODS: Taphonomic assessment of two chimpanzee infants included
      description of breakage and surface modification, data on MNE, %MNE, and bone
      survivorship. Two additional infants were assessed qualitatively. The data were
      compared to published information on monkey prey. We also undertook a review of
      published infanticide cases. RESULTS: The cases were intercommunity infanticides
      (one male and three female infants) committed by males. Attackers partially
      consumed two of the victims. Damage to all four infants included puncture marks
      and compression fractures to the cranium, crenulated breaks to long bones, and
      incipient fractures on ribs. Compared to monkey prey, the chimpanzee infants had
      an abundance of vertebrae and hand/foot bones. CONCLUSIONS: The cases described
      here suggest that chimpanzees may not always completely consume infanticide
      victims, while reports on chimpanzee predation indicated that complete
      consumption of monkey prey usually occurred. Infanticidal chimpanzees undoubtedly
      gain nutritional benefits when they consume dead infants, but this benefit may
      not sufficiently explain infanticide in this species. Continued study of
      infanticidal and hunting behavior, including skeletal analysis, is likely to be
      of interest.

PMID- 29072311
TI  - Modifications of the National Early Warning Score for patients with chronic
      respiratory disease.
AB  - BACKGROUND: The National Early Warning Score (NEWS) uses physiological variables
      to detect deterioration in hospitalized patients. However, patients with chronic
      respiratory disease may have abnormal variables not requiring interventions. We
      studied how the Capital Region of Denmark NEWS Override System (CROS), the
      Chronic Respiratory Early Warning Score (CREWS) and the Salford NEWS (S-NEWS)
      affected NEWS total scores and NEWS performance. METHODS: In an observational
      study, we included patients with chronic respiratory disease. The frequency of
      use of CROS and the NEWS total score changes caused by CROS, CREWS and S-NEWS
      were described. NEWS, CROS, CREWS and S-NEWS were compared using 48-h mortality
      and intensive care unit (ICU) admission within 48 h as outcomes. RESULTS: We
      studied 11,266 patients during 25,978 admissions; the use of CROS lowered NEWS
      total scores in 40% of included patients. CROS, CREWS and S-NEWS had lower
      sensitivities than NEWS for 48-h mortality and ICU admission. Specificities and
      PPV were higher. CROS, CREWS and S-NEWS downgraded, respectively, 51.5%, 44.9%
      and 32.8% of the NEWS total scores from the 'mandatory doctor presence' and
      'immediate doctor presence and specialist consultation' total score intervals to
      lower intervals. CONCLUSION: Capital Region of Denmark NEWS Override System was
      frequently used in patients with chronic respiratory disease. CROS, CREWS and S
      NEWS reduced sensitivity for 48-h mortality and ICU admission. Using the
      methodology prevalent in the NEWS literature, we cannot conclude on the safety of
      these systems. Future prospective studies should investigate the balance between
      detection rate and alarm fatigue of different systems, or use controlled designs
      and patient-centred outcomes.

PMID- 29072313
TI  - Please mind the gap - measures to spread research excellence across Europe.

PMID- 29072314
TI  - Hematopoietic (stem) cell development-how divergent are the roads taken?

PMID- 29072312
TI  - Stable isotope analysis of a pre-Hispanic Andean community: Reconstructing pre
      Wari and Wari era diets in the hinterland of the Wari empire, Peru.
AB  - OBJECTIVES: Stable carbon and nitrogen isotope analysis is used to reconstruct
      diet among a pre-Hispanic population from the Peruvian Andes to evaluate whether
      local foodways changed with Wari imperial influence in the region. This study
      also compares local diet to other Wari-era sites. MATERIALS AND METHODS: Samples
      derive from the site of Beringa in Peru and correspond primarily to pre-Wari (200
      600 CE) and Wari (600-1,000 CE). We examine stable carbon isotopes from enamel (n
      = 29) and bone apatite (n = 22), and stable carbon and nitrogen isotopes from
      bone collagen (n = 29), and we present stable carbon and nitrogen isotope data on
      archaeological and modern fauna (n = 37) and plants (n = 19) from the region.
      RESULTS: There were no significant differences in either delta13 C or delta15 N
      from the pre-Wari to Wari era, indicating that those measurable aspects of diet
      did not change with Wari influence. There were no sex-based differences among
      juveniles (as inferred from delta13 C from enamel carbonates) nor among adults
      (based on delta13 C and delta15 N from adult bone collagen). Comparisons to other
      Wari era sites show that Beringa individuals exhibited significantly lower
      delta13 C values, suggesting that they consumed significantly less maize, a
      socially valued food. Further, the Froehle et al. (2012) stable isotope model
      suggests that the majority of the Beringa individuals consumed more C3 than C4
      plants, and dietary protein was derived primarily from terrestrial animals and
      some marine resources. CONCLUSIONS: The similar diets from pre-Wari to Wari times
      hint at strong local dietary traditions and durable food trade networks during
      the period of Wari imperial influence. The presence of limited marine foods in
      the diet suggests a trade network with coastal groups or sojourns to the coast to
      gather marine resources.

PMID- 29072315
TI  - Methyl jasmonate: a phytohormone with potential for the treatment of inflammatory
      bowel diseases.
AB  - OBJECTIVES: The phytohormone methyl jasmonate (MeJA) has been identified as a
      vital cell regulator in plants. This substance is analogous to eicosanoids and
      similar to that of anti-inflammatory prostaglandins. In animals and in animal
      cells, it displayed an efficient neuroprotective, anti-inflammatory and
      antioxidant action; while in tumoral strains, it demonstrates a potentially
      highly attractive mechanism of apoptosis induction through various cellular and
      molecular mechanisms. The aim of the present review was to explore two new
      hypotheses that explain the action of MeJA, a lipid phytohormone and its
      potentially anti-apoptotic mechanism for use as a therapeutic target for future
      treatment of Inflammatory bowel diseases (IBDs). KEY FINDINGS: Methyl jasmonate
      is a new candidate for the treatment of IBDs, modulating the expression of the
      major classes of caspase-type protease families that selectively act on the
      extrinsic and intrinsic pathways of the apoptotic process. Its action is based on
      the reduction of the expression in tumour necrosis factor tissue levels and the
      modulating action of reactive oxygen species production, acting only on the
      destruction of cells that express the diseased phenotype, and preserving cells
      that are not transformed. CONCLUSIONS: Methyl jasmonate may represent an
      alternative for the transduction processes of important signals in the cellular
      renewal of the intestinal mucosa.

PMID- 29072317
TI  - Implanted fiducial markers are no longer needed for prostate cancer radiotherapy.

PMID- 29072316
TI  - Climate drivers and animal host use determine kelp performance over decadal
      scales in the kelp Pleurophycus gardneri (Laminariales, Phaeophyceae).
AB  - Primary producers respond to climate directly and indirectly due to effects on
      their consumers. In the temperate coastal ocean, the highly productive brown
      algae known as kelp have both strong climate and grazer linkages. We analyzed the
      demographic response of the kelp Pleurophycus gardneri over a 25-year span to
      determine the interaction between ocean climate indicators and invertebrate
      infestation rates. Pleurophycus hosts amphipod species that burrow in the stipe,
      increasing mortality. Although kelp performance is generally greater with more
      negative values of the Pacific Decadal Oscillation (PDO) and colder seawater
      temperatures, Pleurophycus showed the opposite pattern. When we compared the
      1990s, a period of positive values for the PDO and warmer sea surface
      temperatures, with the following decade, a period characterized by negative PDO
      values, we documented a contradictory outcome for proxies of kelp fitness. In the
      1990s, Pleurophycus unexpectedly showed greater longevity, faster growth, greater
      reproductive effort, and a trend toward decreased amphipod infestation compared
      with the 2006-2012 period. In contrast, the period from 2006 to 2012 showed
      opposite kelp performance patterns and with a trend toward greater amphipod
      infestation. Pleurophycus performance metrics suggest that some coastal primary
      producers will respond differently to climate drivers, particularly if they
      interact strongly with grazers.

PMID- 29072318
TI  - Cortical beta EEG oscillations related to changes in muscle tone activity during
      sleep in spider monkey (Ateles geoffroyi).
AB  - BACKGROUND: The physiological mechanisms that allow for sleeping in a vertical
      position, which is primordial for arboreal primates, have not been studied yet.
      METHODS: A non-invasive polysomnographic study of 6 spider monkeys (Ateles
      geoffroyi) was conducted. The relative beta power of the motor cortex and its
      linear relation with muscle tone in the facial mentalis muscle and the abductor
      caudae medialis muscle of the tail during wakefulness and sleep stages were
      calculated. RESULTS: A strong negative linear relationship (r = -.8, P = .03) was
      found between the relative power of the beta2 band in the left motor cortex and
      abductor caudae medialis muscle tone during delta sleep. CONCLUSIONS: The left
      motor cortex, through beta2 band activity, interacts with abductor caudae
      medialis muscle tonicity during delta sleep. This interaction takes part in the
      mechanisms that regulate the sleep postures.

PMID- 29072320
TI  - Technical Note: Correction for the effect of breathing variations in CT pulmonary
      ventilation imaging.
AB  - PURPOSE: The accuracy and precision of computed tomography (CT) pulmonary
      ventilation imaging with conventional CT scanners are limited by breathing
      variations. We propose a method to correct for the effect of breathing variations
      in CT ventilation imaging based on external respiratory signals acquired
      throughout a scan. METHODS: The proposed method is based on: (a) calculating
      voxel-by-voxel abdominal surface motion ranges using four-dimensional (4D) CT
      image datasets spatiotemporally correlated with external respiratory monitor
      data, and (b) applying the correction factor, which is defined as the ratio of
      the overall mean of the abdominal surface motion range in the lungs to that of
      each voxel, to the CT ventilation value. The performance of the proposed method
      was investigated by comparing voxel-wise correlations of the uncorrected and
      corrected CT ventilation images with single-photon emission CT (SPECT)
      ventilation images as a ground truth for nine patients. CT ventilation images
      were calculated by deformable image registration of the 4D-CT image datasets,
      followed by calculation of regional volume changes. A Steiger's Z-test was used
      to determine the statistical significance of the difference between the
      correlations for the uncorrected and corrected CT ventilation images. RESULTS:
      The proposed correction method resulted in significant increases (P < 0.05) in
      the correlation between CT and SPECT ventilation in three patients, trends toward
      significant increase (P: 0.13-0.18) in two patients, no significant differences
      in three patients, and a significantly decreased correlation in one patient. The
      average standard deviation of the abdominal surface motion range in three
      patients showing significant increases was 0.27 (range 0.10-0.37), which was
      greater than 0.17 (range 0.07-0.38) in the other six patients. CONCLUSIONS: The
      proposed method to correct for the effect of breathing variations could be
      readily implemented and has the potential to improve the accuracy of CT
      ventilation imaging as demonstrated in a nine-patient study.

PMID- 29072319
TI  - In the mind's eye: The late positive potential to negative and neutral mental
      imagery and intolerance of uncertainty.
AB  - There are many advantages to human beings' ability to generate and sustain mental
      imagery in the absence of exteroceptive stimuli; however, this ability may also
      underlie emotional disorders characterized by worry, rumination, or excessive
      concern about the future. For instance, fear-based disorders may be characterized
      by heightened ERPs to negative imagery. On the other hand, distress disorders may
      be characterized by attempts to avoid engaging with negative mental imagery, and
      therefore reduced electrocortical response. Prior ERP work has used negative and
      neutral pictorial stimuli to establish the parameters of response in healthy
      individuals, before taking these paradigms to clinical samples to assess aberrant
      emotion processing. Yet despite its clinical relevance, no study to date has
      elicited a late positive potential (LPP), a robust measure of emotion processing,
      to standardized negative imagined scenes. Here, participants listened to audio
      descriptions of negative and neutral scenes, and were asked to imagine these
      scenes as vividly as possible. Results showed that negative imagined scenes
      elicited an increased LPP, lasting approximately 10 s after audio description
      offset, as well as heightened ratings of arousal and unpleasantness. Moreover,
      participants with greater self-reported cognitive concerns about uncertain future
      events (higher prospective intolerance of uncertainty) showed reduced emotional
      modulation of the LPP. These data provide the first evidence of sustained
      electrocortical processing of standardized negative imagery elicited in the
      absence of salient visual cues, and suggest that cognitive risk for anxiety in an
      unselected sample may be represented phenotypically by blunted LPPs to negative
      imagery.

PMID- 29072321
TI  - Standardised evaluation of medicine acceptability in paediatric population:
      reliability of a model.
AB  - OBJECTIVES: Our novel tool to standardise the evaluation of medicine
      acceptability was developed using observational data on medicines use measured in
      a paediatric population included for this purpose (0-14 years). Using this tool,
      any medicine may be positioned on a map and assigned to an acceptability profile.
      The present exploration aimed to verify its statistical reliability. METHODS:
      Permutation test has been used to verify the significance of the relationships
      among measures highlighted by the acceptability map. Bootstrapping has been used
      to demonstrate the accuracy of the model (map, profiles and scores of
      acceptability) regardless of variations in the data. Lastly, simulations of
      enlarged data sets (*2; *5; *10) have been built to study the model's
      consistency. KEY FINDINGS: Permutation test established the significance of the
      meaningful pattern identified in the data and summarised in the map.
      Bootstrapping attested the accuracy of the model: high RV coefficients (mean
      value: 0.930) verified the mapping stability, significant Adjusted Rand Indexes
      and Jaccard coefficients supported clustering validity (with either two or four
      profiles), and agreement between acceptability scores demonstrated scoring
      relevancy. Regarding enlarged data sets, these indicators reflected a very high
      consistency of the model. CONCLUSIONS: These results highlighted the reliability
      of the model that will permit its use to standardise medicine acceptability
      assessments.

PMID- 29072322
TI  - Signal enhancement due to high-Z nanofilm electrodes in parallel plate ionization
      chambers with variable microgaps.
AB  - PURPOSE: We developed a method for measuring signal enhancement produced by high
      Z nanofilm electrodes in parallel plate ionization chambers with variable
      thickness microgaps. METHODS: We used a laboratory-made variable gap parallel
      plate ionization chamber with nanofilm electrodes made of aluminum-aluminum (Al
      Al) and aluminum-tantalum (Al-Ta). The electrodes were evaporated on 1 mm thick
      glass substrates. The interelectrode air gap was varied from 3 MUm to 1 cm. The
      gap size was measured using a digital micrometer and it was confirmed by
      capacitance measurements. The electric field in the chamber was kept between 0.1
      kV/cm and 1 kV/cm for all the gap sizes by applying appropriate compensating
      voltages. The chamber was exposed to 120 kVp X-rays. The current was measured
      using a commercial data acquisition system with temporal resolution of 600 Hz. In
      addition, radiation transport simulations were carried out to characterize the
      dose, D(x), high-energy electron current, J(x), and deposited charge, Q(x), as a
      function of distance, x, from the electrodes. A deterministic method was selected
      over Monte Carlo due to its ability to produce results with 10 nm spatial
      resolution without stochastic uncertainties. Experimental signal enhancement
      ratio, SER(G) which we defined as the ratio of signal for Al-air-Ta to signal for
      Al-air-Al for each gap size, was compared to computations. The individual
      contributions of dose, electron current, and charge deposition to the signal
      enhancement were determined. RESULTS: Experimental signals matched computed data
      for all gap sizes after accounting for several contributions to the signal: (a)
      charge carrier generated via ionization due to the energy deposited in the air
      gap, D(x); (b) high-energy electron current, J(x), leaking from high-Z electrode
      (Ta) toward low-Z electrode (Al); (c) deposited charge in the air gap, Q(x); and
      (d) the decreased collection efficiency for large gaps (>~500 MUm). Q(x) accounts
      for the electrons below 100 eV, which are regarded as stopped by the radiation
      transport code but which can move and form electron current in small gaps (<100
      MUm). While the total energy deposited in the air gap increases with gap size for
      both samples, the average high-energy current and deposited charge are moderately
      decreasing with the air gap. When gap sizes are smaller than ~20 MUm, the
      contribution to signal from dose approaches zero while contributions from high
      energy current and deposited charges give rise to an offset signal. The measured
      signal enhancement ratio (SER) was 40.0 +/- 5.0 for the 3 MUm gap and rapidly
      decreasing with gap size down to 9.9 +/- 1.2 for the 21 MUm gap and to 6.6 +/-
      0.3 for the 100 MUm gap. The uncertainties in SER were mostly due to
      uncertainties in gap size and data acquisition system. CONCLUSIONS: We developed
      an experimental method to determine the signal enhancement due to high-Z
      nanolayers in parallel plate ionization chambers with micrometer spatial
      resolution. As the water-equivalent thicknesses of these air gaps are 3 nm to 10
      MUm, the method may also be applicable for nanoscopic spatial resolution of other
      gap materials. The method may be extended to solid insulator materials with low
      Z.

PMID- 29072323
TI  - European Society of Endodontology: Abstracts from the Biennial Congress 2017, 14
      16 September 2017, Brussels, Belgium.

PMID- 29072324
TI  - Juvenile pityriasis rubra pilaris: successful treatment with methotrexate.

PMID- 29072325
TI  - Patients with Primary Sjogren's Syndrome Have Alterations in Absolute Quantities
      of Specific Peripheral Leucocyte Populations.
AB  - An accurate dissection of peripheral blood enumeration is lacking in primary
      Sjogren's syndrome (pSS). The purpose of this study was to quantify different
      leucocyte populations in peripheral blood of patients with pSS. Numbers of
      specific leucocyte subsets were determined in 86 pSS patients and 74 healthy
      donors quantifying 21 distinct subtypes by flow cytometry. Subgroups of pSS
      patients were stratified based on presence of extraglandular manifestations
      (EGMs) and SSA/SSB autoantibodies. Overall, pSS patients manifested decreased
      lymphocyte subpopulations compared to healthy donors. Such decreases were more
      pronounced in SSA/SSB positive patients and patients with EGM. Granulocyte and
      monocyte subpopulations were increased in pSS patients compared to healthy
      donors, with the greatest increases in SSA/SSB positive patients. Unsupervised
      hierarchal clustering based on cell quantities was used to further subgroup the
      pSS patients into four clusters. One of the clusters characterized by higher
      concentrations of NKT cells, CD56hi NK cells, CD20+ CD38- B cells and CD8+ CD38-
      T cells was associated with weaker clinical symptoms than the other clusters,
      possibly marking a milder disease phenotype. In conclusion, our analyses indicate
      significant alterations in the cellular profiles of peripheral blood leucocytes
      in patients with pSS and may help to stratify the patients according to disease
      severity.

PMID- 29072326
TI  - Antimicrobial activity of suspensions and nanoemulsions of citral in combination
      with heat or pulsed electric fields.
AB  - : The application of essential oils in form of nanoemulsions has been proposed as
      a method to improve their solubility in aqueous solutions, and hence their
      antimicrobial activity. The objective of this study was to evaluate the
      antimicrobial activity of citral, applied directly or in combined treatments with
      heat or pulsed electric fields (PEF), as a function of the inoculation procedure
      assayed: (i) a simple, vigorous shaking method by vortex agitation (suspension of
      citral; s-citral) or (ii) the previous preparation of nanoemulsions by the
      emulsion phase inversion (EPI) method (nanoemulsion of citral; n-citral). n
      Citral was more effective in either inhibiting or inactivating Escherichia coli
      O157:H7 Sakai than s-citral. However, when combined with heat, a greater
      synergistic effect was observed with s-citral rather than with n-citral, either
      in lab media (pH 7.0 and 4.0) or apple juice. For instance, while almost 5 log10
      cell cycles were inactivated in apple juice after 15 min at 53 degrees C in the
      presence of 0.1 MUl ml-1 of s-citral, the use of n-citral required 30 min. The
      use of nanoemulsions did not modify the slight synergism observed when citral and
      mild PEF were combined (150 MUs, 30 kV cm-1 ). SIGNIFICANCE AND IMPACT OF THE
      STUDY: The exploration of different delivery systems of antimicrobial compounds
      such as citral in aqueous food products aids in the establishment of successful
      combined treatments for food preservation. While at room temperature, citral in
      form of a nanoemulsion shows a higher antimicrobial activity; its combination
      with heat would imply a partial loss of the outstanding synergistic lethal effect
      achieved when added in suspension form. Therefore, the most suitable procedure to
      magnify the synergism between heat and citral when processing juices would merely
      require an intense homogenization step prior to the combined treatment.

PMID- 29072327
TI  - Impact of mycolic acid deficiency on cells of Corynebacterium glutamicum
      ATCC13869.
AB  - Mycolic acid (MA) plays important role in Corynebacterium glutamicum, but the key
      enzymes in the biosynthetic pathway of MA in C. glutamicum ATCC13869 have not
      been characterized. Since the locus BBD29_RS14045 in C. glutamicum ATCC13869
      shows high similarity to the gene Cgl2871, which encodes Pks13, the key enzyme
      for synthesizing MA in C. glutamicum ATCC13032, it was deleted, resulting in the
      mutant WG001. Compared with the wild-type ATCC13869, MA was not synthesized in
      WG001, but more phosphatidylglycerol and phosphatidylinositol containing longer
      unsaturated fatty acids were produced. WG001 cells also show hindered cell growth
      and defective cell separation when compared with ATCC13869 cells. Transcriptomic
      analysis shows that many genes relevant to the pathways of fatty acids, inositol,
      phospholipids, cell wall, and cell division were significantly regulated in WG001
      cells when compared with ATCC13869 cells. This study demonstrates that the locus
      BBD29_RS14045 encodes a key enzyme that plays important role for synthesizing MA
      in C. glutamicum ATCC13869.

PMID- 29072328
TI  - Aberrations in sperm DNA methylation patterns of males suffering from reduced
      fecundity.
AB  - The purpose of this study was to evaluate the aberrations in sperm DNA
      methylation patterns of males suffering from reduced fecundity. A total of 108
      males (65 males suffering from reduced fecundity as cases and 43 proven fertile
      males as a control) were included in the study. Thirty samples were subjected to
      450K arrays as a screening phase, and then, three CpG sites located in the
      following genes: TYRO3, CGbeta and FAM189A1 were selected to validate on 78
      samples using deep bisulphite sequencing. A significant difference in the
      methylation level was found between cases and controls at all CpGs in TYRO3 gene
      related amplicon (CpG1, p <= .003, CpG2, p <= .0001, CpG3, p <= .003 and CpG4, p
      <= .030) and CpG1 in CGbeta gene-related amplicon (p <= .0001). Besides, a
      significant difference was found at two CpGs (CpG1, p <= .004 and CpG2, p <=
      .002) tested in the FAM189A1 gene-related amplicon. A significant correlation was
      found between the methylation level at CpG1 in the FAM189A1 gene and the
      different types of sperm motility. In conclusion, an alteration in the
      methylation levels of sperm DNA from males with reduced fecundity was showed. In
      addition, a relationship between variations in the methylation level of these
      CpGs and sperm motility has been observed.

PMID- 29072329
TI  - Disciplinary power and the process of training informal carers on stroke units.
AB  - This article examines the process of training informal carers on stroke units
      using the lens of power. Care is usually assumed as a kinship obligation but the
      state has long had an interest in framing the carer and caring work. Training
      carers in healthcare settings raises questions about the power of the state and
      healthcare professionals as its agents to shape expectations and practices
      related to the caring role. Drawing on Foucault's notion of disciplinary power,
      we show how disciplinary forms of power exercised in interactions between
      healthcare professionals and carers shape the engagement and resistance of carers
      in the process of training. Interview and observational field note extracts are
      drawn from a multi-sited study of a training programme on stroke units targeting
      family carers of people with stroke to consider the consequences of subjecting
      caring to this intervention. We found that the process of training informal
      carers on stroke units was not simply a matter of transferring skills from
      professional to lay person, but entailed disciplinary forms of power intended to
      shape the conduct of the carer. We interrogate the extent to which a specific
      kind of carer is produced through such an approach, and the wider implications
      for the participation of carers in training in healthcare settings and the
      empowerment of carers.

PMID- 29072330
TI  - Prenatal diagnosis of chronic intestinal pseudo-obstruction and paternal somatic
      mosaicism for the ACTG2 pathogenic variant.

PMID- 29072331
TI  - Giant chorioangioma treated with interstitial laser coagulation.

PMID- 29072332
TI  - Updates on immunity and inflammation in Parkinson disease pathology.
AB  - Studies in the last decade have suggested the association of both
      neuroinflammatory processes and immune responses in Parkinson disease (PD)
      pathology. PD pathology is related to depleted dopamine levels, alpha-synuclein
      aggregation, and death of nigrostriatal dopaminergic neurons. Reports have
      suggested central and peripheral inflammation in the prodromal stage of the
      disease, which is sustained during disease progression. Alongside the activation
      of peripheral immune system exacerbates the dissonant central inflammatory
      responses and could contribute in synergistic neurodegeneration. Activated glial
      cells contribute significantly in the neuroinflammatory process during the
      occurrence of the disease and are also acknowledged as a hallmark of disease
      progression. However, the contribution of glial cells is not well defined in the
      context of neurodegeneration and neuroprotection. This review provides an
      overview of the roles of immune and inflammatory responses and their consequences
      in PD disease pathogenesis and also discusses possible therapeutic strategies for
      PD based on these findings.

PMID- 29072333
TI  - Large-scale purification of high purity alpha1-antitrypsin from Cohn Fraction IV
      with virus inactivation by solvent/detergent and dry-heat treatment.
AB  - alpha1-Antitrypsin (AAT) is widely used to treat patients with congenital AAT
      deficiency. Cohn Fraction IV (Cohn F IV) is normally discarded during the
      manufacturing process of albumin but contains approximately 33% of plasma AAT. We
      established a new process for large-scale purification of AAT from it. liquid
      chromatography-electrospray ionization-tandem mass spectrometry and high
      performance liquid chromatography were applied for qualitative identification and
      composition analysis, respectively. Stabilizers were optimized for AAT activity
      protection during lyophilization and dry-heat. Virus inactivation by dry-heat and
      solvent/detergent (S/D) was validated on a range of viruses. AAT with purity of
      95.54%, specific activity of 3,938.5 IU/mg, and yield of 26.79%, was achieved.
      More than 95% activity was reserved after S/D. More than 96% activity was
      obtained after lyophilization or dry-heat. After S/D, pseudorabies virus (PRV)
      and vesicular stomatitis virus (VSV) were inactivated below detectable level
      within 1 H. Virus titer reductions of more than 5.50 log10 and 5.38 log10 were
      achieved for PRV and VSV, respectively. Porcine parvovirus and
      encephalomyocarditis virus were inactivated by 3.17 log10 and 5.88 log10
      reduction after dry-heat. The advantages of this process, including suitability
      for large-scale production, high purity, better utilization of human plasma,
      viral safety, commercial and inexpensive chromatography medium, may facilitate
      its further application.

PMID- 29072334
TI  - Protective efficacy of an IL-12-expressing baculoviral malaria vaccine.
AB  - Interleukin-12 (IL-12) plays an important role in antigen-specific adaptive
      immunity against Plasmodium sporozoites, and this requirement allows for a new
      approach to developing an effective malaria vaccine. In this study, we examined
      whether IL-12 could enhance protective efficacy of a baculovirus-based malaria
      vaccine. For this aim, a baculoviral vector expressing murine IL-12 (mIL-12)
      under the control of CMV promoter (BES-mIL-12-Spider) and a baculoviral vector
      expressing Plasmodium falciparum circumsporozoite protein (PfCSP) with post
      transcriptional regulatory element of woodchuck hepatitis virus (BDES-sPfCSP2
      WPRE-Spider) were generated. BES-mIL-12-Spider produced bioactive IL-12 which
      activates splenocytes, resulting in induction of IFN-gamma. When co-immunized
      with BES-mIL-12-Spider and BDES-sPfCSP2-WPRE-Spider, the mouse number for high
      IgG2a/IgG1 ratios and the geometric mean in this group were both increased as
      compared with those of the other groups, indicating a shift towards a Th1-type
      response following immunization with BES-mIL-12-Spider. Finally, immunization
      with BDES-sPfCSP2-WPRE-Spider plus BES-mIL-12-Spider had a higher protective
      efficacy (73%) than immunization with BDES-sPfCSP2-WPRE-Spider alone (30%)
      against challenge with transgenic Plasmodium berghei sporozoites expressing
      PfCSP. These results suggest that co-administration of IL-12 expressing
      baculoviral vector, instead of IL-12 cDNA, with viral-vectored vaccines provides
      a new feasible vaccine platform to enhance Th1-type cellular immune responses
      against Plasmodium parasites.

PMID- 29072335
TI  - Spatial distribution of buffy-tufted-ear (Callithrix aurita) and invasive
      marmosets (Callithrix spp.) in a tropical rainforest reserve in southeastern
      Brazil.
AB  - We investigated the spatial distribution of native and invasive marmoset species
      (Callithrix), as well as their hybrids, in the Serra dos Orgaos National Park
      (PARNASO) and surrounding area in Rio de Janeiro state, Brazil. To estimate
      occupancy and the detection probability, we surveyed 56 sites within the park and
      52 sites outside its limits using vocal playbacks, as well as by interviewing
      local residents in the surrounding area. We estimated the occupancy and detection
      probability of Callithrix aurita and the observed groups composed of Callithrix
      jacchus, Callithrix penicillata, and their hybrids. We also recorded the presence
      or absence of mixed groups of native and exotic species, and their hybrids. We
      recorded similar occupancy rates and detection probabilities for both native and
      invasive species within the national park. C. aurita was found more often within
      the areas of the park located furthest from access roads and with the least human
      interference, while invasive species were more likely to be found along the edge
      of the park and in areas with greater human interference. In the area surrounding
      the park, invasive marmosets were recorded at seven sites, and a mixed group of
      native and invasive marmosets was observed at one site, but non-hybrid C. aurita
      groups were not recorded. The occupancy probability of C. aurita in the study
      area is relatively low, which may indicate a low population density, with groups
      restricted to a small region within the PARNASO in the proximity of groups of
      invasive marmosets.

PMID- 29072336
TI  - Mechanisms of toxicity associated with six tyrosine kinase inhibitors in human
      hepatocyte cell lines.
AB  - Tyrosine kinase inhibitors have revolutionized the treatment of certain cancers.
      They are usually well tolerated, but can cause adverse reactions including liver
      injury. Currently, mechanisms of hepatotoxicity associated with tyrosine kinase
      inhibitors are only partially clarified. We therefore aimed at investigating the
      toxicity of regorafenib, sorafenib, ponatinib, crizotinib, dasatinib and
      pazopanib on HepG2 and partially on HepaRG cells. Regorafenib and sorafenib
      strongly inhibited oxidative metabolism (measured by the Seahorse-XF24 analyzer)
      and glycolysis, decreased the mitochondrial membrane potential and induced
      apoptosis and/or necrosis of HepG2 cells at concentrations similar to steady
      state plasma concentrations in humans. In HepaRG cells, pretreatment with
      rifampicin decreased membrane toxicity (measured as adenylate kinase release) and
      dissipation of adenosine triphosphate stores, indicating that toxicity was
      associated mainly with the parent drugs. Ponatinib strongly impaired oxidative
      metabolism but only weakly glycolysis, and induced apoptosis of HepG2 cells at
      concentrations higher than steady-state plasma concentrations in humans.
      Crizotinib and dasatinib did not significantly affect mitochondrial functions and
      inhibited glycolysis only weakly, but induced apoptosis of HepG2 cells. Pazopanib
      was associated with a weak increase in mitochondrial reactive oxygen species
      accumulation and inhibition of glycolysis without being cytotoxic. In conclusion,
      regorafenib and sorafenib are strong mitochondrial toxicants and inhibitors of
      glycolysis at clinically relevant concentrations. Ponatinib affects mitochondria
      and glycolysis at higher concentrations than reached in plasma (but possibly in
      liver), whereas crizotinib, dasatinib and pazopanib showed no relevant toxicity.
      Mitochondrial toxicity and inhibition of glycolysis most likely explain
      hepatotoxicity associated with regorafenib, sorafenib and possibly pazopanib, but
      not for the other compounds investigated.

PMID- 29072337
TI  - Synthetic Approaches to Trifluoromethylselenolated Compounds.
AB  - The association of trifluoromethyl group to chalcogens gives new fluorinated
      substituents with specific properties, mainly in term of lipophilicity. The
      trifluoromethylselenyl group is the last of the series that has been studied and
      despite pioneering approaches in the late 1960s, CF3 Se chemistry has been
      scarcely developed over the last decades. Some modern and efficient methods to
      obtain trifluoromethylselenolated molecules have recently emerged. This Review
      describes the advancements that have been reported.

PMID- 29072339
TI  - An insight into the possible mechanisms of antispermatogenic action of Dalbergia
      sissoo in male mice.
AB  - This study investigated the possible mechanisms of antispermatogenic action of
      Dalbergia sissoo in Parkes male mice. Mice were orally administered aqueous leaf
      extract of Dalbergia sissoo (50 and 100 mg kg-1 body weight day-1 for 35 days)
      and various testicular indices such 3beta- and 17beta-hydroxysteroid
      dehydrogenase (HSD) activities, Western blot analyses of StAR, cytochrome P450scc
      and caspase-3, germ cell apoptosis by TUNEL, and lipid peroxidation and
      antioxidant enzymes activities were assessed. A significant increase in lipid
      peroxidation level and a marked decrease in activities of superoxide dismutase,
      catalase, 3beta- and 17beta-HSD were noted in the testis of Dalbergia-treated
      mice compared to controls. The treatment also had adverse effect on expression
      levels of StAR and cytochrome P450scc in the testis. There was an increase in the
      number of TUNEL-positive germ cells and in expression level of caspase-3 in
      testes of Dalbergia-treated mice, especially in those treated with 100 mg dose
      compared to controls. By 56 days of withdrawal therapy, the alterations induced
      in the above parameters recovered to control levels. Our results thus suggest
      that Dalbergia treatment interferes with steroidogenesis and produces oxidative
      stress in the testis, which may induce germ cell apoptosis leading to suppression
      of spermatogenesis.

PMID- 29072338
TI  - Determination of lipid bilayer affinities and solvation characteristics by
      electrokinetic chromatography using polymer-bound lipid bilayer nanodiscs.
AB  - Styrene-maleic acid polymer-bound lipid bilayer nanodiscs have been investigated
      and characterized by electrokinetic chromatography. Linear solvation energy
      relationship analysis was employed to characterize the changes in solvation
      environment of nanodiscs of varied belt to lipid ratio, belt polymer chemistry
      and molecular weight, and lipid composition. Increases in the lipid to belt
      polymer ratio resulted in smaller, more cohesive nanodiscs with greater
      electrophoretic mobility. Nanodisc structures with belt polymers of different
      chemistry and molecular weight were compared and showed only minor changes in
      solvent characteristics and selectivity consistent with changes in structure of
      the lipid bilayer. Seven phospholipid and sphingomyelin nanodiscs of different
      lipid composition were characterized. Changes in lipid head group structure had a
      significant effect on bilayer-solute interactions. In most cases, changes in
      alkyl tail structure had no discernible effect on solvation environment aside
      from those explained by changes in the gel-liquid transition temperature.
      Comparison to vesicles of similar lipid composition show only minor differences
      in solvation environment, likely due to differences in lipid composition and
      bilayer curvature. Together these results provide evidence that the dominant
      solute-nanodisc interactions are with the lipid bilayer and that head group
      chemistry has a greater impact on bilayer-solute interactions than alkyl tail or
      belt polymer structure. Nanodisc electrokinetic chromatography is demonstrated to
      allow characterization of solute interactions with lipid bilayers of varied
      composition.

PMID- 29072340
TI  - Cyclic Hydroxamic Acid Analogues of Bacterial Siderophores as Iron-Complexing
      Agents prepared through the Castagnoli-Cushman Reaction of Unprotected Oximes.
AB  - The first application of multicomponent chemistry (the Castagnoli-Cushman
      reaction) toward the convenient one-step preparation of cyclic hydroxamic acids
      is described. Cyclic hydroxamic acids are close analogues of bacterial
      siderophores (iron-binding compounds) and form stable complexes with Fe3+ ions as
      confirmed by spectrophotometric measurements. These compounds are potential
      components for the design of chelating agents for iron overload disease therapy,
      as well as siderophore-based carrier systems for antibiotic delivery across the
      bacterial cell wall.

PMID- 29072341
TI  - Perspectives on the underlying drivers of urgent and emergency care
      reconfiguration in Ireland.
AB  - BACKGROUND: There is an increasing tendency to reconfigure acute hospital care
      towards a more centralised and specialised model, particularly for complex care
      conditions. Although centralisation is presented as "evidence-based", the
      relevant studies are often challenged by groups which hold perspectives and
      values beyond those implicit in the literature. This study investigated
      stakeholder perspectives on the rationale for the reconfiguration of urgent and
      emergency care in Ireland. Specifically, it considered the hypothesis that
      individuals from different stakeholder groups would endorse different positions
      in relation to the motivation for, and goals of, reconfiguration. METHODS:
      Documentary analysis of policy documents was used to identify official
      justifications for change. Semi-structured interviews with 175 purposively
      sampled stakeholders explored their perspectives on the rationale for
      reconfiguration. RESULTS: While there was some within-group variation, internal
      and external stakeholders generally vocalised different lines of argument.
      Clinicians and management in the internal stakeholder group proposed arguments in
      favour of reconfiguration based on efficiency and safety claims. External
      stakeholders, including hospital campaigners and local political representatives
      expressed arguments that focused on access to care. A "voter" argument, focused
      on the role of local politicians in determining the outcome of reconfiguration
      planning, was mentioned by both internal and external stakeholders, often in a
      critical fashion. CONCLUSION: Our study adds to an emerging literature on the
      interaction between a technocratic approach to health system planning advocated
      by clinicians and health service managers, and the experiential "non-expert"
      claims of the public and patients.

PMID- 29072342
TI  - Use of long-term data to evaluate loss and endangerment status of Natura 2000
      habitats and effects of protected areas.
AB  - Habitat loss is a key driver of biodiversity loss. However, hardly any long-term
      time series analyses of habitat loss are available above the local scale for
      finer-level habitat categories. We analysed, from a long-term perspective, the
      habitat specificity of habitat-area loss, the change in trends in habitat loss
      since 1989 (dissolution of the communist state), and the impact of protected
      areas on habitat loss in Hungary. We studied 20 seminatural habitat types in 5000
      randomly selected localities over 7 periods from 1783 to 2013 based on historical
      maps, archival and recent aerial photos and satellite imagery, botanical
      descriptions, and field data. We developed a method for estimating habitat types
      based on information transfer between historical sources (i.e., information from
      a source was used to interpret or enrich information from another source). Trends
      in habitat loss over time were habitat specific. We identified 7 types of habitat
      loss over time regarding functional form: linear, exponential, linear and
      exponential, delayed, minimum, maximum, and disappearance. Most habitats had
      continuous loss from period to period. After 1986 the average annual rates of
      habitat loss increased, but the trend reversed after 2002. Nature conservation
      measures significantly affected habitat loss; net loss was halted, albeit only
      inside protected areas. When calculating the degree of endangerment based on
      short-term data (52 years), we classified only 1 habitat as critically
      endangered, but based on long-term data (230 years), this increased to 7
      (including habitat that no longer existed). Hungary will probably reach the
      global Convention on Biological Diversity Target 5 but will probably not achieve
      the EU Biodiversity Strategy target of halting habitat loss by 2020. Long-term
      trend data were highly useful when we examined recent habitat-loss data in a
      wider context. Our method could be applied effectively in other countries to
      augment shorter-term data sets on trends in habitat area.

PMID- 29072343
TI  - Low-Cost and Scaled-Up Production of Fluorine-Free, Substrate-Independent, Large
      Area Superhydrophobic Coatings Based on Hydroxyapatite Nanowire Bundles.
AB  - To date, the scaled-up production and large-area applications of superhydrophobic
      coatings are limited because of complicated procedures, environmentally harmful
      fluorinated compounds, restrictive substrates, expensive equipment, and raw
      materials usually involved in the fabrication process. Herein, the facile, low
      cost, and green production of superhydrophobic coatings based on hydroxyapatite
      nanowire bundles (HNBs) is reported. Hydrophobic HNBs are synthesised by using a
      one-step solvothermal method with oleic acid as the structure-directing and
      hydrophobic agent. During the reaction process, highly hydrophobic C-H groups of
      oleic acid molecules can be attached in situ to the surface of HNBs through the
      chelate interaction between Ca2+ ions and carboxylic groups. This facile
      synthetic method allows the scaled-up production of HNBs up to about 8 L, which
      is the largest production scale of superhydrophobic paint based on HNBs ever
      reported. In addition, the design of the 100 L reaction system is also shown. The
      HNBs can be coated on any substrate with an arbitrary shape by the spray-coating
      technique. The self-cleaning ability in air and oil, high-temperature stability,
      and excellent mechanical durability of the as-prepared superhydrophobic coatings
      are demonstrated. More importantly, the HNBs are coated on large-sized practical
      objects to form large-area superhydrophobic coatings.

PMID- 29072344
TI  - The effect of sex and prematurity on the cardiovascular baroreflex response in
      sheep.
AB  - NEW FINDINGS: What is the central question of this study? Late preterm infants
      are often assumed to escape long-term morbidities known to impact earlier preterm
      offspring. Is this true for the cardiovascular system? What is the main finding
      and its importance? We show that late preterm birth is a risk factor for
      cardiovascular dysfunction in early adulthood and is influenced by sex. Early
      signs of cardiovascular dysfunction might predispose to heart disease in
      adulthood. Very preterm infants have an increased risk of cardiovascular disease;
      however, the effects of a late preterm birth on future cardiovascular function
      are not known. We hypothesized that after a late preterm birth, the well
      described impairments in heart rate variability and baroreflex sensitivity would
      persist into adulthood. To test this hypothesis, sheep born preterm (0.9
      gestation; nine male and seven female) or term (11 male and six female) underwent
      surgery at 14 months of age for insertion of femoral arterial and venous
      catheters and a femoral flow probe. After recovery, heart rate variability was
      assessed, followed by a baroreflex challenge (using the vasoactive agents
      phenylephrine and sodium nitroprusside) in conscious adult lambs. Our data
      demonstrate decreased low-frequency normalised units (LFnu) and low
      frequency/high-frequency ratio in female but not male ex-preterm sheep at rest.
      When challenged, mature male ex-preterm sheep have an increased blood pressure
      response but dampened heart rate baroreflex response. We show that even a late
      preterm birth leads to cardiovascular dysfunction in adulthood. These early signs
      of cardiovascular dysfunction might underpin the later hypertension and increased
      risk of heart disease observed in adults born preterm. These findings are
      particularly important because late preterm infants are often assumed to escape
      the long-term morbidities known to impact on very preterm and extremely preterm
      offspring.

PMID- 29072345
TI  - Rational Design of Branched Au-Fe3 O4 Janus Nanoparticles for Simultaneous
      Trimodal Imaging and Photothermal Therapy of Cancer Cells.
AB  - We report a facile and simple hydrogen reduction method to fabricate PEGylated
      branched gold (Au)-iron oxide (Fe3 O4 ) Janus nanoparticles (JNPs). Note that the
      hydrogen induces the formation of Fe3 O4 during the synthesis process. Due to the
      strong absorption in the near-infrared range, branched Au-Fe3 O4 JNPs showed a
      significant photothermal effect with a 40 % calculated photothermal transduction
      efficiency under a laser irradiation of 808 nm in vitro. Owing to their excellent
      optical and magnetic properties, branched Au-Fe3 O4 JNPs were demonstrated to be
      advantageous agents for triple-modal magnetic resonance imaging
      (MRI)/photoacoustic imaging (PAI)/computed tomography (CT) in vitro. Therefore,
      the synthetic approach could be extended to prepare Au-metallic oxide JNPs for
      specific applications.

PMID- 29072347
TI  - Technical Note: Dosimetric impact of spherical applicator size in IntrabeamTM
      IORT for treating unicentric breast cancer lesions.
AB  - PURPOSE: To characterize the dosimetric impact of using different sizes of
      spherical applicators in IntrabeamTM Intraoperative Radiation Therapy (IB-IORT)
      to treat unicentric cancer lesions after breast-conserving lumpectomy. METHODS:
      Using the commissioned depth dose rates, the three-dimensional dosages of the
      3.5, 4.0, 4.5, and 5.0 cm spherical applicators of the IB-IORT PRS400 machine
      were established. Five different cancer cell infiltration depths of unicentric
      breast lesions were formulated by a linearly declining cancer cell density
      distribution from the surgical surface. The equivalent uniform dose (EUD), which
      is the dosage of a homogeneous dose treatment for killing the same amount of
      cancer cells as IB-IORT in the same target volume, was then calculated using the
      modified linear quadratic model (MLQ). The radiobiological response of two types
      of cancer cell lines and three types of normal tissues in the TARGIT-A clinical
      trial of 20 Gy dose was estimated. The study was carried out for an acutely
      responding breast cancer cell line with an alpha/beta ratio of 10 and a slow
      responding breast cancer cell line with an alpha/beta ratio of 3.85,
      respectively. The cancer cell density at the surgical excision surface was
      assumed to be 0.01%, 0.1%, 1%, and 10%, respectively. The three types of normal
      tissue are radiosensitive, moderate radiosensitive, and radioresistant,
      respectively. The therapeutic ratio (TR), which was defined by a ratio between
      the survival fractions of normal tissue cells respectively in IB-IORT and in
      homogeneous dose treatments, was calculated. RESULTS: The EUDs are moderately
      dependent on the applicator size (increasing from 1 to 10% depending on the
      cancer infiltrating depth when increasing diameter by 0.5 cm), not on the cancer
      cell radiosensitivity (differing by less than 1.30% between two cancer cell
      lines), and not dependent on the cancer cell population density at the surgical
      excision surface (differing by 0% among the tested surface densities). The EUDs
      decrease with the cancer cell maximum infiltrating depth. EUD of a 10 mm
      spherical shell target volume is about 50% of EUD of a 1 mm spherical shell. TRs
      are dependent on the applicator size, cancer cell infiltrating depth, and the
      radiosensitivities of cancer cells and normal tissue. A smaller size of
      applicator was found to produce a greater TR for a shallowly seated lesion (<5
      mm), while a large size of applicator is better to treating a deeply seated
      lesion (>5 mm). CONCLUSIONS: The applicator size has a moderate impact on the
      EUDs, a greater size of applicator will deliver a greater EUD at the same cancer
      cell infiltrating depth, but a smaller size of applicator is seen to produce a
      greater TR for the shallow lesions (depth <5 mm). In addition, a greater size of
      applicator is preferred for treating a deeply seated lesion (depth >5 mm) because
      it produces a greater TR and EUD than a smaller size of applicator. IB-IORT is a
      preferable alternative to uniform dose treatment when treating unicentric breast
      cancer at smaller infiltration depths.

PMID- 29072346
TI  - Effects of modified abutment characteristics on peri-implant soft tissue health:
      A systematic review and meta-analysis.
AB  - OBJECTIVES: The purpose of this systematic review was to evaluate the impact of
      the abutment characteristics on peri-implant tissue health and to identify the
      most suitable material and surface characteristics. METHODS: A protocol was
      developed aimed to answer the following focused question: "Which is the effect of
      the modification of the abutment design in regard to the maintenance of the peri
      implant soft tissue health?" Further subanalysis aimed to investigate the impact
      of the abutment material, macroscopic design, surface topography and surface
      manipulation. Randomised controlled trials (RCTs) with a follow-up of at least 6
      months after implant loading were considered as inclusion criteria. Meta-analyses
      were performed whenever possible. RESULTS: Nineteen final publications from
      thirteen investigations were included. The results from the meta-analysis
      indicated that zirconia abutments (Zi) experienced less increase in BOP values
      over time [n = 3; WMD = -26.96; 95% CI (-45.00; -8.92); p = .003] and less plaque
      accumulation [n = 1; MD = -20.00; 95% CI (-41.47; 1.47); p = .068] when compared
      with titanium abutments (Ti). Bone loss was influenced by the method of abutment
      decontamination [n = 1; MD = -0.44; 95% CI (-0.65; -0.23); p < .001]. The rest of
      the studied outcomes did not show statistically significant differences.
      CONCLUSIONS: The macroscopic design, the surface topography and the manipulation
      of the implant abutment did not have a significant influence on peri-implant
      inflammation. In contrast, the abutment material demonstrated increased BOP
      values over time for Ti when compared to Zi abutments.

PMID- 29072348
TI  - Natural-Product-Derived Carbon Dots: From Natural Products to Functional
      Materials.
AB  - Nature provides an almost limitless supply of sources that inspire scientists to
      develop new materials with novel applications and less of an environmental
      impact. Recently, much attention has been focused on preparing natural-product
      derived carbon dots (NCDs), because natural products have several advantages.
      First, natural products are renewable and have good biocompatibility. Second,
      natural products contain heteroatoms, which facilitate the fabrication of
      heteroatom-doped NCDs without the addition of an external heteroatom source.
      Finally, some natural products can be used to prepare NCDs in ways that are very
      green and simple relative to traditional methods for the preparation of carbon
      dots from man-made carbon sources. NCDs have shown tremendous potential in many
      fields, including biosensing, bioimaging, optoelectronics, and photocatalysis.
      This Review addresses recent progress in the synthesis, properties, and
      applications of NCDs. The challenges and future direction of research on NCD
      based materials in this booming field are also discussed.

PMID- 29072350
TI  - Transition-Metal-Free Catalytic Hydrodefluorination of Polyfluoroarenes by
      Concerted Nucleophilic Aromatic Substitution with a Hydrosilicate.
AB  - A transition-metal-free catalytic hydrodefluorination (HDF) reaction of
      polyfluoroarenes is described. The reaction involves direct hydride transfer from
      a hydrosilicate as the key intermediate, which is generated from a hydrosilane
      and a fluoride salt. The eliminated fluoride regenerates the hydrosilicate to
      complete the catalytic cycle. Dispersion-corrected DFT calculations indicated
      that the HDF reaction proceeds through a concerted nucleophilic aromatic
      substitution (CSN Ar) process.

PMID- 29072349
TI  - Functional characterization of O-methyltransferases used to catalyse site
      specific methylation in the post-tailoring steps of pradimicin biosynthesis.
AB  - AIMS: To identify the roles of the two O-methyltransferase homologous genes pdmF
      and pdmT in the pradimicin biosynthetic gene cluster of Actinomadura hibisca P157
      2. METHODS AND RESULTS: Pradimicins are pentangular polyphenol antibiotics
      synthesized by bacterial type II polyketide synthases (PKSs) and tailoring
      enzymes. Pradimicins are naturally derivatized by combinatorial O-methylation at
      two positions (i.e., 7-OH and 11-OH) of the benzo[alpha]naphthacenequinone
      structure. PdmF and PdmT null mutants (PFKO and PTKO) were generated. PFKO
      produced the 11-O-demethyl shunt metabolites 11-O-demethylpradimicinone II (1),
      11-O-demethyl-7-methoxypradimicinone II (2), 11-O-demethylpradimicinone I (3) and
      11-O-demethylpradimicin A (4), while PTKO generated the 7-O-demethyl derivatives
      pradimicinone II (5) and 7-hydroxypradimicin A (6). Pradimicinones 1, 2, 3, and 5
      were fed to a heterologous host Escherichia coli harbouring expression plasmid
      pET-22b::pdmF or pET-28a::pdmT. PdmF catalysed 11-O-methylation of pradimicinones
      1, 2, and 3 regardless of O-methylation at the C-7 position, while PdmT was
      unable to catalyse 7-O-methylation when the C-11 hydroxyl group was methylated
      (5). CONCLUSIONS: PdmF and PdmT were involved in 11-O- and 7-O-methylations of
      the benzo[alpha]naphthacenequinone moiety of pradimicin, respectively.
      Methylation of the C-7 hydroxyl group precedes methylation of the C-11 hydroxyl
      group in pradimicin biosynthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: This is
      the first reported demonstration of the functions of PdmF and PdmT for
      regiospecific O-methylation, which contributes to better understanding of the
      post-PKS modifications in pradimicin biosynthesis as well as to rational
      engineering of the pradimicin biosynthetic machinery.

PMID- 29072351
TI  - Conducting research through cross national collaboration.
AB  - AIM: To explore the collaborative nature of an international research project
      with other advanced practice nurse researchers and critically analyse the
      process. BACKGROUND: Research within the nursing community is recognized
      internationally as important to ensure that nurses participate in cutting-edge
      health care and promote evidence-based practices, yet there is little detail
      found in literature on how a successful collaborative relationship is initiated
      and conducted in advanced practice research. DESIGN: Discussion paper: The
      purpose of this paper is to discuss the process of collaboration on a research
      study among advanced practice nurses from four countries who are members of an
      international organization. IMPLICATIONS FOR NURSING: The collaborative process
      in international nursing research can be challenging and rewarding. It is
      important to remember that there is a relationship between the complexity of the
      study and the time required to complete it. Keys to success include following
      established guidelines. CONCLUSION: This project was a valuable experience in
      developing collaborative relationships as well as creating partnerships for
      future research to build on the knowledge gained. The authors' linkages to
      universities facilitated their participation in the research and completion of
      the ethical review processes. The use of social media and university resources
      was indispensable.

PMID- 29072353
TI  - An integrative literature review on midwives' perceptions on the facilitators and
      barriers of physiological birth.
AB  - AIM: To present a synthesis and summary of midwives' perceptions on the
      facilitators and barriers of physiological birth. BACKGROUND: Medicalisation of
      birth has transformed and dictated how birthing should take place since the 20th
      century. Midwives' perceptions on their role within this medicalised environment
      have not been well documented. DESIGN: An integrative literature review. DATA
      SOURCES AND REVIEW METHODS: Primary research articles published in English from
      the period of 2004 to 2015 were included in this review. The Joanna Briggs
      Institute's critical appraisal forms were used to appraise the quality of the
      articles. Data were identified from CINAHL, PubMed, PsycINFO, ScienceDirect, and
      Scopus. RESULTS: Eighteen articles were reviewed. Lack of knowledge due to
      inadequate training, existing obstetrician-led practices, and midwives' negative
      perceptions of physiological birth were identified as barriers in the literature.
      Facilitators like shared decision-making, women's preferences, teamwork,
      institutional support, and midwives' positive perceptions of physiological birth
      promoted physiological birth. Most of the studies were conducted in Western
      countries. CONCLUSION: Midwives face barriers and facilitators when promoting
      physiological birth during their clinical practise. Future studies exploring
      midwives' perceptions of physiological birth are needed, especially in Asia where
      cultural and organizational factors may differ from Western countries.

PMID- 29072352
TI  - Development of a Potential Protein Display Platform in Corynebacterium glutamicum
      Using Mycolic Acid Layer Protein, NCgl1337, as an Anchoring Motif.
AB  - In the cell surface display, the choice of host cell and anchoring motif are the
      most crucial for the efficient display of passenger proteins. Corynebacterium
      glutamicum has mycolic acid layer in outer membrane and the use of protein in the
      mycolic acid layer as an anchoring motif can provide a potential platform for
      surface display in C. glutamicum. All 19 mycolic acid layer proteins of C.
      glutamicum are analyzed, and two proteins, NCgl0535 and NCgl1337, which have a
      signal peptide and predicted O-mycoloylation site, are selected as anchoring
      motifs candidates. Among them, NCgl1337, which shows better expression with
      higher display efficiency, is chosen as a potential anchoring motif. Two forms of
      the NCgl1337 anchoring motif, a full-length (1-324 amino acids) and a short
      length (1-50 amino acids) containing only signal peptide and O-mycoloylation
      site, are constructed and their abilities for surface display are examined using
      two protein models, endoxylanase from Streptomyces coelicolor and alpha-amylase
      from Streptococcus bovis. For both model proteins, the short-length NCgl1337
      anchoring motif exhibits higher yield of protein display on the surface of C.
      glutamicum than the full-length NCgl1337. Finally, with C. glutamicum displaying
      alpha-amylase, a batch fermentation is performed for the production of l-lysine
      from starch degradation, and a production of l-lysine as high as 10.8 +/- 0.92 g
      L-1 was achieved after 18 h of culture.

PMID- 29072354
TI  - cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down
      regulation of TC10 activity at the plasma membrane and neurite outgrowth.
AB  - Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a
      trafficking system supplies membrane at growth cones. However, the cAMP-induced
      signaling leading to the regulation of membrane trafficking remains unknown. TC10
      is a Rho family GTPase that is essential for specific types of vesicular
      trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF
      treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and
      TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP
      addition in neuronal cells. TC10 was locally inactivated at extending neurite
      tips in cAMP-treated PC12 cells. TC10 depletion led to a decrease in cAMP-induced
      neurite outgrowth. Constitutively active TC10 could not rescue this growth
      reduction, supporting our model for a role of GTP hydrolysis of TC10 in
      neuritogenesis by accelerating vesicle fusion. The cAMP-induced TC10 inactivation
      was mediated by PKA. Considering cAMP-induced RhoA inactivation, we found that
      p190B, but not p190A, mediated inactivation of TC10 and RhoA. Upon cAMP
      treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1
      N17 expression reduced cAMP-induced TC10 inactivation. Together, the PKA-STEF
      Rac1-p190B pathway leading to inactivation of TC10 and RhoA at the plasma
      membrane plays an important role in cAMP-induced neurite outgrowth.

PMID- 29072355
TI  - Quantitative Prediction of Rate Constants for Aqueous Racemization To Avoid
      Pointless Stereoselective Syntheses.
AB  - Racemization has a large impact upon the biological properties of molecules but
      the chemical scope of compounds with known rate constants for racemization in
      aqueous conditions was hitherto limited. To address this remarkable blind spot,
      we have measured the kinetics for racemization of 28 compounds using circular
      dichroism and 1 H NMR spectroscopy. We show that rate constants for racemization
      (measured by ourselves and others) correlate well with deprotonation energies
      from quantum mechanical (QM) and group contribution calculations. Such
      calculations thus provide predictions of the second-order rate constants for
      general-base-catalyzed racemization that are usefully accurate. When applied to
      recent publications describing the stereoselective synthesis of compounds of
      purported biological value, the calculations reveal that racemization would be
      sufficiently fast to render these expensive syntheses pointless.

PMID- 29072356
TI  - Proton-Coupled Reduction of the Catalytic [4Fe-4S] Cluster in [FeFe]
      Hydrogenases.
AB  - In nature, [FeFe]-hydrogenases catalyze the uptake and release of molecular
      hydrogen (H2 ) at a unique iron-sulfur cofactor. The absence of an
      electrochemical overpotential in the H2 release reaction makes [FeFe]
      hydrogenases a prime example of efficient biocatalysis. However, the molecular
      details of hydrogen turnover are not yet fully understood. Herein, we
      characterize the initial one-electron reduction of [FeFe]-hydrogenases by
      infrared spectroscopy and electrochemistry and present evidence for proton
      coupled electron transport during the formation of the reduced state Hred'.
      Charge compensation stabilizes the excess electron at the [4Fe-4S] cluster and
      maintains a conservative configuration of the diiron site. The role of Hred' in
      hydrogen turnover and possible implications on the catalytic mechanism are
      discussed. We propose that regulation of the electronic properties in the
      periphery of metal cofactors is key to orchestrating multielectron processes.

PMID- 29072358
TI  - Symptoms at presentation to the emergency department: Predicting outcomes and
      changing clinical practice?
AB  - BACKGROUND: The type and number of symptoms in emergency patients differ widely.
      It remains unclear, if outcomes can be predicted by the number of symptoms.
      Furthermore, it is unknown, whether clinical practice could be influenced by
      presenting symptoms. METHODS: Prospective observational study, performed in the
      emergency department of the University Hospital Basel, a tertiary hospital. A
      consecutive sample of patients was interviewed at presentation for a predefined
      set of 35 symptoms. The number of symptoms was correlated with outcomes using
      linear and logistic regression models. Clinical practice was observed using
      prospective data on disease severity ratings, triage category, use of resources,
      length-of-stay and follow-up presentations. RESULTS: Data of 3472 patients were
      analysed. The number of symptoms ranged between 1 and 25, the mean being 2.74.
      Women reported more symptoms than men. Age and comorbidity indices were not
      associated with the number of symptoms. After adjusting for age and gender, there
      was no correlation between the number of symptoms and adverse outcomes, such as
      ICU-admission or in-hospital mortality (OR: 1.03, CI: 0.88-1.18, P = .68). The
      number of symptoms at presentation was associated with hospitalisation, disease
      severity rating by patients and emergency physicians, triage categories, use of
      resources, length-of-stay and follow-up presentations. CONCLUSION: The number of
      symptoms did not correlate with the main adverse outcomes (ICU-admission and in
      hospital mortality). However, clinical practice was influenced by the nature and
      number of symptoms. This was shown by associations with hospitalisation, length
      of-stay, use of resources and follow-up presentations. Furthermore, the number of
      symptoms correlated with the caregivers' disease severity ratings and the
      attributed triage categories. This may indicate that caregivers respond to the
      number of symptoms by a higher investment in their immediate work-ups and later
      follow-ups.

PMID- 29072357
TI  - Piper regnellii extract biopolymer-based microparticles: production,
      characterization and antifungal activity.
AB  - AIMS: This study aims to improve characteristics of Piper regnellii extract to
      make it applicable in formulations to treat dermatophytosis, also known as
      ringworm. METHODS AND RESULTS: Microparticles (MPs) were produced by spray drying
      with gelatin, alginate and chitosan as encapsulating agents; characterized by
      scanning electron microscopy, encapsulation efficiency, thermal analyses and X
      ray diffraction; and tested against Trichophyton rubrum by broth microdilution.
      Produced MPs had a mean diameter less than 2 MUm, an increase in stability and
      release of the extract and good results for encapsulation efficiency, being 85.6%
      to gelatin MP, 71.3% to chitosan MP and 60.6% to alginate. MPs preserved the
      antifungal activity of P. regnellii extract T. rubrum. CONCLUSION:
      Microencapsulation provided a significant improvement in the stability of the P.
      regnellii extract and better solubilization of chemical compounds, maintaining
      the antifungal effect against T. rubrum. SIGNIFICANCE AND IMPACT OF THE STUDY:
      These results are useful for developing a formulation to treat fungal infections
      caused by dermatophyte species.

PMID- 29072359
TI  - Fungal extracellular phosphatases: their role in P cycling under different pH and
      P sources availability.
AB  - AIMS: The aim of this work is to analyse the effect of pH, fungal identity and P
      chemical nature on microbial development and phosphatase release, discussing
      solubilization and mineralization processes in P cycling. METHODS AND RESULTS: P
      solubilizing fungi (Talaromyces flavus, T. helicus L, T. helicus N, T. diversus
      and Penicillium purpurogenum) were grown under three pH conditions (6, 6.5 and
      8.5) and with different inorganic (calcium, iron, aluminium and rock) and organic
      (lecithin and phytate) P sources. P solubilization, mineralization, growth and
      phosphatase production were recorded. Acid and neutral environments maximized
      fungal development and P recycling. P chemical nature changed the phosphatases
      release pattern depending on the fungal identity. Acid phosphatase activity was
      higher than alkaline phosphatases, regardless of pH or sample times. Alkaline
      phosphatases were affected by a combination of those factors. CONCLUSIONS: P
      chemical nature and pH modify fungal growth, P mineralization and solubilization
      processes. The underlying fungal identity-dependent metabolism governs the
      capacity and efficiency of P solubilization and mineralization. P solubilization
      and mineralization processes are interrelated and simultaneously present in soil
      fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study constitutes a reference
      work to improve the selection of fungal bioinoculants in different environmental
      conditions, highlighting their role in P cycling.

PMID- 29072360
TI  - Mobile phase effects on the retention on polar columns with special attention to
      the dual hydrophilic interaction-reversed-phase liquid chromatography mechanism,
      a review.
AB  - Hydrophilic interaction liquid chromatography on polar columns in aqueous-organic
      mobile phases has become increasingly popular for the separation of many
      biologically important compounds in chemical, environmental, food, toxicological,
      and other samples. In spite of many new applications appearing in literature, the
      retention mechanism is still controversial. This review addresses recent progress
      in understanding of the retention models in hydrophilic interaction liquid
      chromatography. The main attention is focused on the role of water, both adsorbed
      by the column and contained in the bulk mobile phase. Further, the theoretical
      retention models in the isocratic and gradient elution modes are discussed. The
      dual hydrophilic interaction liquid chromatography reversed-phase retention
      mechanism on polar columns is treated in detail, especially with respect to the
      practical use in one- and two-dimensional liquid chromatography separations.

PMID- 29072361
TI  - Multi-Component Uptake of Dye Molecules by Films of Nanoporous Metal-Organic
      Frameworks.
AB  - Nanoporous materials, such as metal-organic frameworks (MOFs), enable the
      separation of various molecular mixtures. Thus, detailed knowledge of multi
      component diffusion properties of the guest molecules in the pores is vital.
      Here, UV/Vis absorption spectroscopy combined with step-by-step-synthesized MOF
      films with high transparency are used to measure the multi-component dye uptake
      and diffusion in a straightforward fashion. The time-resolved single-component,
      binary- and ternary-mixture uptakes of methylene blue (MB), nuclear fast red
      (NFR) and acid yellow 17 (AY) by MOF films of type HKUST-1 from ethanolic
      solutions with low dye concentrations were investigated. It was found that the
      diffusion of MB is approximately one order of magnitude slower than the diffusion
      of NFR or AY, independent of whether it is a single-component uptake or a mixture
      uptake.

PMID- 29072362
TI  - Clinical effectiveness and cost-effectiveness of nurse-led care in Chinese
      patients with rheumatoid arthritis: A randomized trial comparing with
      rheumatologist-led care.
AB  - BACKGROUND AND AIM: The concept of nurse-led care (NLC) was not familiar in
      China. This study was designed to evaluate the clinical effectiveness and cost
      effectiveness of NLC versus rheumatologist-led care (RLC) in Chinese patients
      with rheumatoid arthritis (RA). METHODS: Patients of either gender (aged >=18
      years) with RA were enrolled at Wenhai Central Hospital, China (January 2015 to
      December 2015). The participants were then randomized to NLC or RLC. Outcomes of
      both the groups were compared in terms of effectiveness by measuring the Disease
      Activity Score 28, visual analogue scores pertaining to pain and fatigue, and
      duration of morning stiffness. Costs associated with resource use for RA were
      assessed and compared between both groups. RESULTS: A total of 214 RA patients in
      2 groups (n = 107 in each group) were enrolled and analysed. Improvements in
      clinical outcomes (disease activity, pain, fatigue, and morning stiffness) over
      12 months were significantly greater in the NLC group compared to RLC (P <
      0.001). Overall, costs associated with resource use were higher in the RLC group
      compared to the NLC group (P < 0.05). CONCLUSIONS: Our preliminary finding
      suggested that RA patients managed by NLC compared to RLC may have better
      clinical outcomes and more cost-effective care in China.

PMID- 29072363
TI  - Poor performance of main-stream capnography in newborn infants during general
      anesthesia.
AB  - BACKGROUND: Endtidal (ET) measurement of carbon dioxide is well established for
      intraoperative respiratory monitoring of adults and children, but the method's
      accuracy for intraoperative use in small newborn infants has been less
      extensively investigated. AIMS: The aim of this study was to compare carbon
      dioxide from ET measurements with arterialized capillary blood samples in newborn
      infants during general anesthesia and surgery. METHODS: Endtidal carbon dioxide
      was continuously measured during anesthesia and surgery and compared with
      simultaneous blood gas analyses obtained from capillary blood samples. Fifty-nine
      sample sets of ET to blood gas carbon dioxide were obtained from 23 prospectively
      enrolled infants with a gestational age of 23-41 weeks and a birth weight of 670
      4110 g. RESULTS: Endtidal levels of carbon dioxide were considerably lower in all
      sample sets and only 4/23 individual ET-blood gas sample pairs differed <7.5 mm
      Hg (1 kPa). Bland-Altman analysis indicated a poor agreement with a bias of -13
      +/- 7 mm Hg and a precision of +/-14 mm Hg. The performance of ET measurements
      was particularly poor in infants weighing below 2.5 kg, in infants in need of
      respiratory support prior to anesthesia, and when the true (blood gas) carbon
      dioxide level was high, above 45 mm Hg. CONCLUSION: Main-stream capnography
      during anesthesia and surgery correlated poorly to blood gas values in small
      and/or respiratory compromised infants. We conclude that caution should be
      exercised when relying solely on ET measurements to guide mechanical ventilation
      in the OR.

PMID- 29072364
TI  - Molecular determinants of beta-adrenergic signaling to voltage-gated K+ channels
      in the cerebral circulation.
AB  - Voltage-gated K+ (Kv ) channels are major determinants of membrane potential in
      vascular smooth muscle cells (VSMCs) and regulate the diameter of small cerebral
      arteries and arterioles. However, the intracellular structures that govern the
      expression and function of vascular Kv channels are poorly understood.
      Scaffolding proteins including postsynaptic density 95 (PSD95) recently were
      identified in rat cerebral VSMCs. Primarily characterized in neurons, the PSD95
      scaffold has more than 50 known binding partners, and it can mediate
      macromolecular signaling between cell-surface receptors and ion channels. In
      cerebral arteries, Shaker-type Kv 1 channels appear to associate with the PSD95
      molecular scaffold, and PSD95 is required for the normal expression and
      vasodilator influence of members of this K+ channel gene family. Furthermore,
      recent findings suggest that the beta1-subtype adrenergic receptor is expressed
      in cerebral VSMCs and forms a functional vasodilator complex with Kv 1 channels
      on the PSD95 scaffold. Activation of beta1-subtype adrenergic receptors in VSMCs
      enables protein kinase A-dependent phosphorylation and opening of Kv 1 channels
      in the PSD95 complex; the subsequent K+ efflux mediates membrane
      hyperpolarization and vasodilation of small cerebral arteries. Early evidence
      from other studies suggests that other families of Kv channels and scaffolding
      proteins are expressed in VSMCs. Future investigations into these macromolecular
      complexes that modulate the expression and function of Kv channels may reveal
      unknown signaling cascades that regulate VSMC excitability and provide novel
      targets for ion channel-based medications to optimize vascular tone.

PMID- 29072366
TI  - Sling now or later?

PMID- 29072365
TI  - Invasive micropapillary carcinoma of the breast has a better long-term survival
      than invasive ductal carcinoma of the breast in spite of its aggressive clinical
      presentations: a comparison based on large population database and case-control
      analysis.
AB  - There are controversies in the comparison of overall survival between invasive
      micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma
      (IDC). The objective of this study was to compare the long-term survival outcome
      between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End
      Results database was searched to identify women with non-metastatic IMPC and IDC
      diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics
      were performed using Pearson's chi-square. The propensity score matching method
      was applied with each IMPC matched to one IDC. Breast cancer-specific survival
      (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product
      limit method and compared across groups using the log-rank statistic.
      Multivariate analysis was performed through Cox models. IMPC was presented with
      aggressive clinical presentations such as larger tumor, more positive lymph
      nodes, and more advanced stage compared with IDC. A higher rate of estrogen
      receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC.
      With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS
      (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an
      independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI:
      0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup
      analysis, IMPC always showed a better survival outcome compared with IDC except
      in AJCC stage I and histologic grade I disease. IMPC has a better long-term
      survival outcome compared with IDC in spite of its highly aggressive clinical
      presentation.

PMID- 29072367
TI  - Reappraisal of metallothionein: Clinical implications for patients with diabetes
      mellitus.
AB  - Reactive oxygen and nitrogen species (ROS and RNS, respectively) are byproducts
      of cellular physiological processes of the metabolism of intermediary nutrients.
      Although physiological defense mechanisms readily convert these species into
      water or urea, an improper balance between their production and removal leads to
      oxidative stress (OS), which is harmful to cellular components. This OS may
      result in uncontrolled growth or, ultimately, cell death. In addition, ROS and
      RNS are closely related to the development of diabetes and its complications.
      Therefore, numerous researchers have proposed the development of strategies for
      the removal of ROS/RNS to prevent or treat diabetes and its complications. Some
      molecules that are synthesized in the body or obtained from food participate in
      the removal and neutralization of ROS and RNS. Metallothionein, a cysteine-rich
      protein, is a metal-binding protein that has a wide range of functions in
      cellular homeostasis and immunity. Metallothionein can be induced by a variety of
      conditions, including zinc supplementation, and plays a crucial role in mediating
      anti-OS, anti-apoptotic, detoxification, and anti-inflammatory effects.
      Metallothionein can modulate various stress-induced signaling pathways (mitogen
      activated protein kinase, Wnt, nuclear factor-kappaB, phosphatidylinositol 3
      kinase, sirtuin 1/AMP-activated protein kinase and fibroblast growth factor 21)
      to alleviate diabetes and diabetic complications. However, a deeper understanding
      of the functional, biochemical, and molecular characteristics of metallothionein
      is needed to bring about new opportunities for OS therapy. This review focuses on
      newly proposed functions of a metallothionein and their implications relevant to
      diabetes and its complications.

PMID- 29072368
TI  - Promoting Photocatalytic Overall Water Splitting by Controlled Magnesium
      Incorporation in SrTiO3 Photocatalysts.
AB  - SrTiO3 is a well-known photocatalyst inducing overall water splitting when
      exposed to UV irradiation of wavelengths <370 nm. However, the apparent quantum
      efficiency of SrTiO3 is typically low, even when functionalized with
      nanoparticles of Pt or Ni@NiO. Here, we introduce a simple solid-state
      preparation method to control the incorporation of magnesium into the perovskite
      structure of SrTiO3 . After deposition of Pt or Ni@NiO, the photocatalytic water
      splitting efficiency of the Mg:SrTiOx composites is up to 20 times higher
      compared to SrTiO3 containing similar catalytic nanoparticles, and an apparent
      quantum yield (AQY) of 10 % can be obtained in the wavelength range of 300-400
      nm. Detailed characterization of the Mg:SrTiOx composites revealed that Mg is
      likely substituting the tetravalent Ti ion, leading to a favorable surface-space
      charge layer. This originates from tuning of the donor density in the cubic
      SrTiO3 structure by Mg incorporation and enables high oxygen-evolution rates.
      Nevertheless, interfacing with an appropriate hydrogen evolution catalyst is
      mandatory and non-trivial to obtain high-performance in water splitting.

PMID- 29072370
TI  - POLE somatic mutations in advanced colorectal cancer.
AB  - Despite all the knowledge already gathered, the picture of somatic genetic
      changes in colorectal tumorigenesis is far from complete. Recently, germline and
      somatic mutations in the exonuclease domain of polymerase epsilon, catalytic
      subunit (POLE) gene have been reported in a small subset of microsatellite-stable
      and hypermutated colorectal carcinomas (CRCs), affecting the proofreading
      activity of the enzyme and leading to misincorporation of bases during DNA
      replication. To evaluate the role of POLE mutations in colorectal carcinogenesis,
      namely in advanced CRC, we searched for somatic mutations by Sanger sequencing in
      tumor DNA samples from 307 cases. Microsatellite instability and mutation
      analyses of a panel of oncogenes were performed in the tumors harboring POLE
      mutations. Three heterozygous mutations were found in two tumors, the c.857C>G,
      p.Pro286Arg, the c.901G>A, p.Asp301Asn, and the c.1376C>T, p.Ser459Phe. Of the
      POLE-mutated CRCs, one tumor was microsatellite-stable and the other had low
      microsatellite instability, whereas KRAS and PIK3CA mutations were found in one
      tumor each. We conclude that POLE somatic mutations exist but are rare in
      advanced CRC, with further larger studies being necessary to evaluate its
      biological and clinical implications.

PMID- 29072369
TI  - Concise Review: Cancer Cells, Cancer Stem Cells, and Mesenchymal Stem Cells:
      Influence in Cancer Development.
AB  - Tumors are composed of different types of cancer cells that contribute to tumor
      heterogeneity. Among these populations of cells, cancer stem cells (CSCs) play an
      important role in cancer initiation and progression. Like their stem cells
      counterpart, CSCs are also characterized by self-renewal and the capacity to
      differentiate. A particular population of CSCs is constituted by mesenchymal stem
      cells (MSCs) that differentiate into cells of mesodermal characteristics. Several
      studies have reported the potential pro-or anti-tumorigenic influence of MSCs on
      tumor initiation and progression. In fact, MSCs are recruited to the site of
      wound healing to repair damaged tissues, an event that is also associated with
      tumorigenesis. In other cases, resident or migrating MSCs can favor tumor
      angiogenesis and increase tumor aggressiveness. This interplay between MSCs and
      cancer cells is fundamental for cancerogenesis, progression, and metastasis.
      Therefore, an interesting topic is the relationship between cancer cells, CSCs,
      and MSCs, since contrasting reports about their respective influences have been
      reported. In this review, we discuss recent findings related to conflicting
      results on the influence of normal and CSCs in cancer development. The
      understanding of the role of MSCs in cancer is also important in cancer
      management. Stem Cells Translational Medicine 2017;6:2115-2125.

PMID- 29072371
TI  - HER2 exon 27 mutations predict worse survival of breast cancer patients,
      especially in HER2-negative patients.
AB  - The aims of this study were to assess the prognostic value of the HER2 exon 27
      mutations in breast cancer patients. Genomic DNA was isolated from peripheral
      blood leukocytes, and then HER2 exon 27 mutations were detected by direct
      sequencing. Survival curves were estimated by Kaplan-Meier curves and the
      differences between the curves were compared by log-rank tests. A total cohort of
      892 female patients with operable primary breast cancer was included in this
      study. The median follow-up was 47 months. Of these 892 patients, 3.7% (33/892)
      had HER2 exon 27 mutations. Patients with the HER2 exon 27 mutations had a
      significant worse recurrence-free survival (RFS, unadjusted hazard ratio [HR]
      2.42; 95% CI: 1.05-5.58; P = 0.032) and distant recurrence-free survival (DRFS,
      unadjusted HR 2.81; 95% CI: 1.21-6.50; P = 0.012) than the patients with the wild
      type exon 27. Among the 673 patients with negative HER2 expression, 24 mutants
      were found. Patients with the HER2 mutations showed a worse RFS (unadjusted HR
      5.08; 95% CI: 2.14-12.02; P < 0.001) and DRFS (unadjusted HR 5.62; 95% CI: 2.36
      13.40; P < 0.001) than those patients with the wild-type exon 27. Furthermore,
      the mutations remained as unfavorable independent predictors for RFS and DRFS.
      Breast cancer patients with HER2 exon 27 mutations have a worse survival,
      especially in HER2-negative patients. HER2-negative patients with HER2 exon 27
      mutations are potential subgroup of breast cancer patients benefiting from HER2
      targeted therapy in future.

PMID- 29072372
TI  - Misoprostol treatment vs expectant management in women with early non-viable
      pregnancy and vaginal bleeding: a pragmatic randomized controlled trial.
AB  - OBJECTIVE: To compare vaginal misoprostol treatment with expectant management in
      early non-viable pregnancy with vaginal bleeding with regard to complete
      evacuation of the uterine cavity within 10 days after randomization. METHODS:
      This was a parallel randomized controlled, open-label trial conducted in Skane
      University Hospital, Sweden. Patients with anembryonic pregnancy or early fetal
      demise (crown-rump length <= 33 mm) and vaginal bleeding were randomly allocated
      to either expectant management or treatment with a single dose of 800 MUg
      misoprostol administered vaginally. Patients were evaluated clinically and by
      ultrasound until complete evacuation of the uterus was achieved (no gestational
      sac in the uterine cavity and maximum anteroposterior diameter of the
      intracavitary contents < 15 mm as measured by transvaginal ultrasound on
      midsagittal view). Follow-up visits were planned at 10, 17, 24 and 31 days.
      Dilatation and evacuation (D&E) was recommended if miscarriage was not complete
      within 31 days, but was performed earlier at patient's request, or if there was
      excessive bleeding as judged clinically. Analysis was by intention to treat. The
      main outcome measure was number of patients with complete miscarriage without D&E
      <= 10 days. RESULTS: Ninety-four patients were randomized to misoprostol
      treatment and 95 to expectant management. After exclusion of three patients and
      withdrawal of consent by two patients in the expectant management group, 90 women
      were included in this group. Miscarriage was complete <= 10 days in 62/94 (66%)
      of the patients in the misoprostol group and in 39/90 (43%) of those in the group
      managed expectantly (risk difference (RD) = 23%; 95% CI, 8-37%). At 31 days, the
      corresponding figures were 81/94 (86%) and 55/90 (61%) (RD = 25%; 95% CI, 12
      38%). Two patients from each group underwent emergency D&E because of excessive
      bleeding and one of these in each group received blood transfusion. The number of
      patients undergoing D&E at their own request was higher in the expectantly
      managed group, 15/90 (17%) vs 3/94 (3%) in the misoprostol group (RD = 14%; 95%
      CI, 4-23%), as was the number of patients making out-of-protocol visits, 50/90
      (56%) vs 27/94 (29%) (RD = 27%; 95% CI, 12-40%). Compared with the expectant
      management group, more patients in the misoprostol group experienced pain (71/77
      (92%) vs 91/91 (100%); RD = 8%; 95% CI, 1-17%) and used painkillers (59/77 (77%)
      vs 85/91 (93%); RD = 17%; 95% CI, 5-29%). No major side effect was reported in
      any group. CONCLUSIONS: In women with early non-viable pregnancy and vaginal
      bleeding, misoprostol treatment is more effective than is expectant management
      for complete evacuation of the uterus. Both methods are safe but misoprostol
      treatment is associated with more pain than is expectant management. Copyright
      (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29072373
TI  - CHO-Omics Review: The Impact of Current and Emerging Technologies on Chinese
      Hamster Ovary Based Bioproduction.
AB  - CHO cells are the most prevalent platform for modern bio-therapeutic production.
      Currently, there are several CHO cell lines used in bioproduction with distinct
      characteristics and unique genotypes and phenotypes. These differences limit
      advances in productivity and quality that can be achieved by the most common
      approaches to bioprocess optimization and cell line engineering. Incorporating
      omics-based approaches into current bioproduction processes will complement
      traditional methodologies to maximize gains from CHO engineering and bioprocess
      improvements. In order to highlight the utility of omics technologies in CHO
      bioproduction, the authors discuss current applications as well as limitations of
      genomics, transcriptomics, proteomics, metabolomics, lipidomics, fluxomics,
      glycomics, and multi-omics approaches and the potential they hold for the future
      of bioproduction. Multiple omics approaches are currently being used to improve
      CHO bioprocesses; however, the application of these technologies is still
      limited. As more CHO-omic datasets become available and integrated into systems
      models, the authors expect significant gains in product yield and quality. While
      individual omics technologies provide incremental improvements in bioproduction,
      the authors will likely see the most significant gains by applying multi-omics
      and systems biology approaches to individual CHO cell lines.

PMID- 29072374
TI  - 2-Hydroxy-4-methylthio butanoic acid and DL-methionine for Japanese quails in
      production.
AB  - An experiment was performed using 1,000 laying Japanese quails to assess the
      availability of two alternative dietary methionine sources. Treatment 01 = Basal
      Feed that is deficient in digestible methionine + cystine (Met + Cys). The other
      treatments were constituted by Met + Cys levels of 0.8, 1.60 and 2.40 g/kg,
      supplemented with DL-Methionine-99%, HMTBA-88% and HMTBA-84%, being 10 treatments
      in total. The following characteristics were studied: feed intake (g/bird/day),
      egg production (egg/day * 100), egg weight (g/egg), egg mass (g/egg), feed
      conversion per egg dozen (kg feed/dozen eggs), feed conversion per egg mass (kg
      feed/kg eggs), relative yolk weight (g/100 g of egg), relative albumen weight
      (g/100 g of egg), relative shell weight (g/100 g of egg), shell thickness (mm)
      and specific gravity (g/cm3 ). In general result comment, supplemental methionine
      sources must be included in the poultry diet. The different methionine sources
      affect the performance of quails, and the increase in the levels within each
      source improves the performance variables. Significant effect was observable on
      performance variables and egg quality variables, being that DLM-99% is superior
      to the other sources. The HMTBA-88% source is superior to the HMTBA-84% source
      for the same aforementioned variables. In conclusion, the bioefficacy values of
      the HMTBA-88% and HMTBA-84% sources compared to the DLM-99% source on an
      equimolar basis were 81 and 79%, respectively, for the performance variables, and
      83 and 74 while the methionine sources were equivalent for the variables related
      to egg quality.

PMID- 29072376
TI  - [PADEH-PORIYA - A CULTURE OF QUALITY AND EXCELLENCE IN THE GALILEE].
AB  - INTRODUCTION: A culture based on quality and excellence is the cornerstone to a
      successful healthcare system. Padeh-Poriya Medical Center integrates clinical
      activity with extensive research, including basic research, clinical research and
      research in the field of nursing, while ensuring high standards expressed in the
      accreditation survey of the Joint Commission International, national quality
      indicators and patient satisfaction surveys of the Ministry of Health. As a
      general medical center, it provides medical services to residents of the Galilee,
      along with continuous development and improvement in quality and range, as well
      as implementation of new technologies. The establishment of the Faculty of
      Medicine in the Galilee contributed to the expansion of academic and research
      activities through the foundation of the Research Unit and the Advanced Research
      Institute. The current issue presents part of the clinical and research
      activities lead by the Medical Center staff, which express the quality,
      excellence and academic culture.

PMID- 29072375
TI  - Efficacy of microneedling with 70% glycolic acid peel vs microneedling alone in
      treatment of atrophic acne scars-A randomized controlled trial.
AB  - BACKGROUND: Microneedling with dermaroller and glycolic acid peels is commonly
      used for treatment of acne scars. OBJECTIVE: To compare efficacy of microneedling
      alone versus combination of microneedling with serial 70% glycolic acid peel in
      management of atrophic acne scars. METHODS & MATERIALS: Sixty patients with
      atrophic acne scars were randomized into group 1 receiving microneedling at 0, 6,
      and 12 weeks and group 2 receiving microneedling at 0, 6, and 12 weeks along with
      70% glycolic acid peel at 3, 9, and 15 weeks. Acne scar scoring was performed by
      a blinded observer using ECCA (Echelle d'evaluation clinique des cicatrices
      d'acne) scoring at baseline and after 22 weeks. Additionally, patients were asked
      to grade the improvement in acne scars and skin texture on visual analogue scale
      (VAS). RESULTS: Of 60 patients, 52 completed the 22-week study period. The
      decrement from baseline in mean ECCA score was more in group 2 as compared to
      group 1 (39.65+/-2.50 vs 29.58+/-0.18; P<.001). Group 2 also showed more
      improvement in skin texture as compared to group 1 on VAS. CONCLUSION: Addition
      of sequential 70% glycolic acid peel to microneedling gives better scar
      improvement as compared to microneedling alone. In addition to this, it also
      improves skin texture.

PMID- 29072377
TI  - [CONGENITAL ILEAL STENOSIS: LATE CLINICAL MANIFESTATIONS OF EARLY PRENATAL
      SUSPICION].
AB  - INTRODUCTION: Congenital stenosis (partial obstruction) of the small intestine is
      uncommon in comparison to atresia (complete obstruction). The clinical
      manifestations of stenosis could be delayed up to several weeks post-delivery. We
      present a case wherein a baby with a prenatal ultrasound examination showed a
      suspicious picture of small bowel obstruction. However, the clinical
      manifestations after delivery and imaging studies were misleading and non
      classic; therefore, the resection of the stenotic portion of the ileum was
      delayed until the baby was one month of age. After the operation the baby stopped
      vomiting but diarrhea continued. The infant's formula was changed to formula
      containing medium chain triglyceride (MCT) instead of long chain triglyceride
      which proved effective in stopping the diarrhea. We emphasis the importance of
      including the differential diagnosis of congenital obstruction in any baby with
      vomiting (especially bile stain vomiting) despite the fact that the baby had
      diarrhea and not constipation and the imaging studies were not obvious.

PMID- 29072378
TI  - [PRIMARY AND SECONDARY HYPERPARATHYROIDISM PRESENTING AS BROWN TUMOR].
AB  - INTRODUCTION: Hyperparathyroidism (HPT) may lead to the formation of osteolytic
      lesions with giant granulomas. Giant cell lesions associated with HPT are known
      as brown tumor and represent an end stage complication of HPT. Brown tumors
      affect the mandible, clavicles, ribs and pelvis. Maxillary involvement is rare.
      We present two cases of brown tumor: the first is a case of primary HPT involving
      the maxilla and the second case is secondary HPT involving the mandible.
      Differential diagnosis, work up and methods of management of the jaw lesions are
      discussed.

PMID- 29072379
TI  - [EARLY RATHER THAN IMMEDIATE PCI IN NSTEMI; IS TIME EQUAL TO MUSCLE ONCE AGAIN?]
AB  - BACKGROUND: Current guidelines advocate immediate vs. non-immediate percutaneous
      coronary intervention (PCI) strategy in ST elevation vs. non ST elevation
      myocardial infarction (STEMI, NSTEMI). There is however increasing concern that
      "next-day PCI" in NSTEMI may adversely affect LV systolic and/or diastolic
      function and a more urgent aggressive approach should be taken in NSTEMI, similar
      to that in STEMI. In the current study we compared echocardiographic data between
      patients with STEMI and NSTEMI who had either primary or early PCI respectively.
      METHODS: Prospective data of 165 consecutive patients with an acute MI were
      analyzed. Patients had primary PCI if they had STEMI and non-emergent PCI if they
      had NSTEMI. Demographic information, laboratory test results, procedure time and
      post-PCI echocardiographic assessment were compared between the two groups.
      RESULTS: Patients with STEMI were younger compared to patients with NSTEMI. Time
      to intervention was significantly longer in NSTEMI, reflecting guideline derived
      intervention strategy (1.9+/-1.7days, (median 1day) vs. 30+/-15min, for NSTEMI
      and STEMI, respectively, p<0.00001). Post-interventional LV systolic ejection
      fraction was better in NSTEMI compared to STEMI (53+/-14 vs. 48+/-13,
      respectively, p<0.05). Left atrial diameter, mitral inflow parameters and
      pulmonary arterial pressure were similar between the two groups. CONCLUSIONS:
      Adherence to practice guidelines delaying PCI up to 72 hours in patients with
      NSTEMI did not adversely affect left ventricular systolic and/or diastolic
      function compared to immediate PCI in patients with STEMI. Based on current data,
      we conclude that early PCI intervention rather than an immediate one is
      appropriate in NSTEMI patients.

PMID- 29072380
TI  - [COMPARISON OF CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF ARAB AND JEWISH
      CHILDREN LIVING IN THE GALILEE WHO HAVE SUFFERED FROM AN INTESTINAL INFECTION
      CAUSED BY CAMPYLOBACTER].
AB  - INTRODUCTION: Among all infectious agents that cause gastrointestinal infection
      in children, the most common is the Campylobacter bacterium. The bacterium has
      multiple virulence factors such as motility, adhesion and invasion of the human
      intestinal lining, and enzyme secretion. In recent years, there has been a
      worldwide increase in Campylobacter resistance to antibiotics. AIMS: To examine
      the frequency of Campylobacter among children who were hospitalized at the Poriya
      Medical Center during 2012-2014 and suffered from an intestinal infection caused
      by Campylobacter; to compare the demographic, clinical, and laboratory data of
      Jewish and Arab children; to examine the resistance rate of the bacterium to
      antibiotics. METHODS: The data on Campylobacter frequency in children who
      suffered from an intestinal infection was extracted from the medical records:
      age, sex, hospitalization duration, hemoglobin and leukocyte values in blood
      chemistry, the residential environment, and antibiotic treatment during
      hospitalization. In addition, antibiotic susceptibility tests were performed for
      Erythromycin and Ciprofloxacin for all Campylobacter cultures that were isolated
      from patients' stool samples and kept frozen. RESULTS: Campylobacter is the most
      prevalent bacterial factor among children who were hospitalized following
      enteritis. There are differences in the bacterium frequency among Jewish children
      in comparison to frequency in Arab children in the following aspects:
      Campylobacter is more frequent in Arab children, more common among children
      living in rural areas, and especially those of Arab origin. Arab children were
      hospitalized for longer durations than Jewish children. The mean age of Jewish
      children who suffered from infection caused by Campylobacter was higher compared
      to the mean age of Arab children. No difference was found in leukocyte values in
      the cell count. Hemoglobin values were lower among Jewish children compared to
      Arab children. There was a high percentage of children treated with antibiotics
      due to intestinal infection caused by Campylobacter, especially among Arab
      children. Resistance to Erythromycin was not found; however the rate of
      resistance to Ciprofloxacin was 10.7%. CONCLUSIONS: There are significant
      differences in intestinal infection caused by Campylobacter among Jewish and Arab
      children in parameters such as: mean age, hospitalization duration, and
      residential area. The antibiotic resistance rate that was found is low; however,
      presently, it still exists.

PMID- 29072381
TI  - [SUDDEN CARDIAC DEATH IN A YOUNG ADULT WITH DIFFUSE CORONARY ARTERY DISEASE].
AB  - INTRODUCTION: We present a very unusual case in which a high-school student was
      admitted to our cardiac center unconscious and intubated after suffering from out
      of hospital SCD. There was no history of fever, substance abuse, family history
      of sudden cardiac death and/or coronary artery disease, arthralgia,
      hypercoagulable state or familial hyperlipidemia. An emergent coronary angiogram
      revealed diffuse obstructive coronary artery disease which was treated with
      several stents. The following days of his admission were characterized by
      hemodynamic instability, necessitating temporary support via extracorporeal
      membrane oxygenation (ECMO), from which he was weaned off at a later stage. A
      full work-up regarding the etiology of the premature coronary artery disease was
      negative including cardiac magnetic resonance imaging, yet an empirical steroids
      course trial was given. Eventually, the patient regained full recovery, both
      cardiac and neurological, and returned to his usual daily activities. BACKGROUND:
      Diffuse coronary artery disease at a young age, manifesting itself as sudden
      cardiac death (SCD) is a rare event.

PMID- 29072382
TI  - [AN ELECTRONIC PATIENT RECORD (EPR) - "A STING IN THE TAIL" (E-IATROGENESIS):
      PRIMUM NON NOCERE].
AB  - INTRODUCTION: Use of Electronic Patient records is most efficient but careless
      use can result in harm to the patient caused by advanced technology - E
      Iatrogenesis. Correct use of the electronic systems can reduce the amount of
      technology-related errors in the Electronic Patient record. Beyond all doubt,
      handwritten medical records can contribute to human error due to unclear
      handwriting, unclear phrases, etc. Moreover, physical files can be lost or
      misplaced thus making it difficult to retrieve patient history.

PMID- 29072383
TI  - [RESISTANCE OF HELICOBACTER PYLORI TO ANTIBIOTICS IN ISRAEL: PAST VS PRESENT].
AB  - INTRODUCTION: Helicobacter Pylori (H. Pylori) is a spiral shaped Gram-negative
      bacterium which is known to cause chronic gastric inflammation (gastritis) that
      could develop into a gastric or duodenal ulcer. The standard first line therapy
      for H. Pylori infection is a 7-14 days period of "triple therapy" consisting of
      proton pump inhibitors (PPI) and the antibiotics clarithromycin and amoxicillin
      or metronidazole. Recently there has been an increase in H. Pylori resistance to
      antibiotic treatment. Throughout the years 1999, 2002, 2010, 2013 and 2014
      studies have been conducted in Israel that examined H. Pylori resistance rates
      for commonly used antibiotics. These studies included 40-138 participants who
      were diagnosed with infection caused by H. Pylori. Based on information derived
      from these studies, there is a clear increase in H. Pylori resistance to
      antibiotics, particularly to tetracycline, amoxicillin and clarithromycin.

PMID- 29072384
TI  - [GLOBAL INCIDENCE AND RISK FACTORS OF ORAL CANCER].
AB  - INTRODUCTION: Cancer of the oral cavity (Oral cancer) is the 11th most common
      malignancy in the world. Despite the general global trend of a slight decrease in
      the incidence of oral cancer, tongue cancer incidence is increasing. The
      incidence and mortality caused by this tumor show variability according to the
      geographic location in which it is diagnosed. However, in the last decade an
      increase was observed in the percentage of young patients, especially patients
      with tongue cancer. The main risk factors of head and neck cancer worldwide are
      smoking and alcohol, as well as DNA oncogenic viruses and habits, such as betel
      nut. METHODS: Data were collected from worldwide databases, such as Survival
      Epidemiology and End Result (SEER), The National Center of Health Statistics
      (NCHS) and GLOBCAN (2012) IARC. RESULTS: In 2012, 369,200 new cases of oral
      cancer were reported worldwide, with two-thirds of the tumors diagnosed in
      developing countries. These tumors are responsible for approximately 145,328
      deaths worldwide per year. The highest incidence of these cancers is mainly
      reported in South and Southeast Asia and some countries in southern Europe.
      Prevalence and clinical pattern of OSCC varies greatly, depending on geographical
      location while diagnosed. DISCUSSION: As described in our review, the incidence
      of and mortality due to oral tumors pose a significant health problem in many
      aspects all around the world, and differences exist in the behavior of these
      tumors. We witnessed more cases of anterior tongue cancers mainly affecting the
      young age patient group. Several countries in Europe showed a significant
      increase in oral cancer prevalence, such as in Germany. Studies have reported an
      alarming lack of awareness about oral cancer, its symptoms, causes, and these
      gaps in knowledge need to be addressed by further public education, possibly
      targeted to high-risk groups. With the awareness to risk factors, primary
      prevention through the elimination of tobacco consumption, moderation of alcohol
      intake and chemoprevention are urgently needed.

PMID- 29072385
TI  - [MEDICAL CLOWNS: THE TRIPLE VALUE - CLOWN-PARENT-PREMATURE NEONATE].
AB  - INTRODUCTION: The infant's brain develops rapidly during the prenatal and early
      postnatal period. Temporary new neural circuits appear, such as the sub-cortical
      plate (SCP). SCP links the thalamus and cortex in a time window of sensory
      circuits' intensive development, creating the basis for the infant's bonding
      interactions. SCP activity in premature neonates is vulnerable and hypoxic injury
      may have a long lasting influence on brain development. Preterm birth is an
      emotional trauma for the parents and may lead to depression, anxiety and stress.
      This has an impact on the family, effecting parents' function and adaption to
      their new role, and the development of deep emotional bonds with their infant.
      Parent-infant negative interaction in NICU or later may lead to non-functional
      parenthood, hence, early intervention in NICU is important and may improve
      parental function and bonding with the infant. Humor has positive effects on
      human physical and mental health. There has been a fast increase in the number of
      medical clowns in clinical departments, and research shows that the medical clown
      is effective in enhancing medical efficiency. However, as yet, there is no
      scientific evidence regarding medical clowns in the NICU. In the NICU, medical
      clowns create an imaginary triangle by connecting to the parents and their
      premature neonate, based on a sensory-emotional common denominator and a common
      language for clinical purposes. The medical clown's clinical model is based on
      five components related to the parents and the infant. These components serve as
      a human bridge linking the infant entourage/surrounding. Research based on
      objective indexes is necessary to evaluate the efficiency of medical clowns for
      parent-infant bonding and the significance of medical clowns for infant
      development.

PMID- 29072386
TI  - [GENETIC DISORDERS OF RENAL PHOSPHATE HANDLING].
AB  - INTRODUCTION: Hereditary disorders of renal phosphate handling comprise a diverse
      group of genetic diseases, usually characterized by excessive urinary phosphate
      wasting and a negative phosphate balance. In the minority of cases, perturbations
      of renal phosphate handling are associated with excessive urinary phosphate
      reabsorption, leading to pathological hyperphosphatemia. Inorganic phosphate is
      an essential mineral in the human body, playing a crucial role in cellular
      metabolism and skeletal mineralization. Whole body phosphate balance is
      maintained by a highly controlled equilibrium between intestinal uptake, skeletal
      deposition and renal excretion. The human kidney plays a crucial role in
      phosphate homeostasis. The bulk filtered phosphate is reabsorbed in the renal
      proximal tubule by two specialized phosphate transporters, NaPi-IIa and NaPi-IIc.
      Phosphate balance is regulated by dietary phosphate intake, and by the action of
      the parathyroid hormone, vitamin D3 and fibroblast growth factor-23 (FGF-23). All
      these regulators exert their effect by modulating the activity of the proximal
      tubular phosphate transporters, NaPi-IIa and NaPi-IIc. Based on the versatile
      molecular mechanism underlying various renal phosphate wasting disorders, these
      diseases can be divided into three main subgroups: (1) primary impairment of
      proximal tubular phosphate transporters; (2) disorders of FGF-23 metabolism; (3)
      generalized dysfunction of the proximal tubule, also known as renal Fanconi
      syndrome. The clinical similarity between various renal phosphate wasting
      disorders, combined with their rarity, pose a diagnostic and therapeutic
      challenge. Recent advancement in molecular biology has led to the identification
      of the genetic basis of many disorders in this group, has improved our
      understanding of underlying disease mechanisms, and enables accurate genetic
      diagnosis. Nevertheless, the current therapy of most renal phosphate wasting
      disorders is mainly supportive, with limited capacity to change their natural
      course.

PMID- 29072387
TI  - [BIOLOGIC THERAPY FOR JUVENILE IDIOPATHIC ARTHRITIS].
AB  - INTRODUCTION: Juvenile Idiopathic Arthritis (JIA) includes a group of systemic
      inflammatory disorders of unknown etiology for which no curative treatment
      currently exists. The traditional treatment for these disorders which includes
      the use of NSAIDs and disease modifying anti-rheumatic drugs (DMRADs) is only
      effective in a subset of patients. Recent advances in understanding the
      pathophysiology of the inflammatory response, have led to the development of a
      new class of medications, termed biologic agents which are capable of selectively
      inhibiting the principal mediators of inflammation. The introduction of biologic
      drugs has opened a new era in the treatment of rheumatic disorders in children.
      In this review we describe the characteristics of the currently available
      biologic agents in Israel, and the updated information regarding indications,
      efficacy and the safety of these drugs in pediatric patients. Disclosure:
      Consultant and participating in clinical trials for Novartis com.

PMID- 29072388
TI  - [THE CELLULAR MECHANISMS OF LUNG EDEMA CLEARANCE: DOES THE ALVEOLAR EPITHELIUM
      PLAY A ROLE?]
AB  - INTRODUCTION: Pulmonary edema develops as a result of either alteration in the
      hydrostatic and oncotic pressure gradients across the pulmonary circulation and
      the lung interstitium or due to increased lung permeability. Alveolar fluid
      clearance is important in keeping the airspaces free of edema. This process is
      carried out via the alveolar epithelial active transport of Na+ across the
      alveolo-capillary barrier mostly by apical Na+ channels and basolateral Na,K
      ATPases. Several pharmacologic agents such as catecholamines, vasopressin and
      gene therapy interventions have currently been found to stimulate the active Na+
      transport and lung edema clearance. While others such as amiloride, ouabain, high
      tidal volume ventilation, hyperoxia and sepsis decrease the rate of alveolar
      fluid clearance. In conclusion, this review discusses the mechanisms and signal
      pathways by which the alveolar epithelium impacts lung edema clearance.

PMID- 29072389
TI  - [OPTIMIZATION OF TREATMENT BY ANTIBODIES AGAINST TNF-alpha IN INFLAMMATORY BOWEL
      DISEASE].
AB  - INTRODUCTION: Treatment selection for inflammatory bowel disease involves many
      considerations. Anti-TNF - alpha agents are one of the major available
      therapeutic tools for these diseases. Loss of response to anti- TNF - alpha
      agents is relatively common and results mostly, but not exclusively, from the
      development of immunogenicity against the drug. Assessment of disease activity in
      parallel to measurement of drug levels and anti-drug antibodies allows for
      treatment optimization in patients who develop clinical loss of response. For
      patients in remission, treatment optimization can be performed by the evaluation
      of risk factors for disease flare assisted by assessment of drug levels and the
      presence of antibodies. Various algorithms can be used to make a decision that
      will lead to better clinical outcomes and a better cost-effectiveness ratio.
      Professor Yehuda Chowers has received consultancy fees from Abbot and Schering
      Plough.

PMID- 29072390
TI  - Impact of Her-2 Overexpression on Survival of Patients with Metastatic Breast
      Cancer
AB  - Introduction: Breast cancer is a complex and heterogeneous disease which is
      increasingly important as a publichealth problem. In Brazil, 57,960 new cases
      have been estimated to be the burden in 2016 and 2017. Despite advancesin early
      diagnosis and therapy, approximately 20-30% of patients, even with early stage
      lesions, will develop distantmetastatic disease. Tumors with similar clinical and
      pathological presentations may have differing behavior, so itis important to
      understand specific biological characteristics. Objective: To investigate tumor
      markers of primarytumors featuring pleural metastasis to identify organ-specific
      characteristics of metastatic breast cancer. Methods:In a historical cohort
      study, immunohistochemistry was performed on cell blocks of neoplastic pleural
      effusions andresults were compared with clinicopathological data. Results: The
      median survival time with Her-2 overexpressionin malignant pleural effusions was
      2.2 months, whereas cases without overexpression survived, on average, for
      sevenmonths (p = 0.02). Conclusions: We emphasize that metastases may behave
      independently of primary tumors, but thepresent results indicate that therapeutic
      agents targeting Her-2 overexpression could increase survival in metastaticbreast
      cancer cases.

PMID- 29072391
TI  - Analysis of ARID2 Gene Mutation in Oral Squamous Cell Carcinoma
AB  - Background: The ARID2 gene, encoding a sub unit of the chromatin remodelling
      complex, has a possible tumoursuppressor function and has been found to be
      frequently mutated in various tumours, including gingivo buccal oralsquamous cell
      carcinomas. The present study was designed to analyse the presence of ARID2 gene
      mutations in thedistinct genetic South Indian (Dravidian) population. Materials
      and Methods: Genomic DNA from thirty biopsytissue samples of histopathologically
      confirmed cases of oral squamous cell carcinoma (OSCC) were subjected to
      PCRamplification with intronic primers encompassing exons 19 and 20 of ARID2.
      Subsequently, the PCR amplicons werepurified and subjected to Sanger sequencing
      using forward primers for analysis of mutational status. Results: Ourstudy
      yielded a 6% occurrence of mutations in the ARID2 gene among the thirty OSCC
      samples. Two samples showeda C(5174)A nonsense mutation whereby the "C"
      nucleotide was substituted with an "A" nucleotide at position 5174,resulting in
      the conversion of serine amino acid at codon 1725 to a premature STOP codon.
      Conclusion: Identificationof ARID2 gene mutations in OSCCs in this distinct
      ethnic population reaffirms that aberrations in the chromatinremodelling complex
      could indeed also contribute to tumorigenesis, thus providing new insights for
      future research.

PMID- 29072392
TI  - Genetic Polymorphisms of Fas/FasL Promoter Associated with Hepatitis C cirrhosis
      and HCC
AB  - Aim: The present study was performed to determine any associations of genetic
      polymorphisms of Fas/FasL promoterregions, at Fas670 and Fas1377 and FasL844,
      with hepatitis C cirrhosis and HCC, with a focus on severity of disease.Methods:
      Totals of 120 patients with cirrhosis and 101 with hepatocellular carcinoma (HCC)
      were enrolled. All hadchronic HCV infection as indicated by positive anti-HCV
      antibodies and positive HCV RNA on real time PCR. Onehundred healthy control
      subjects were also included in the study. Patients were subjected to full
      clinical, radiologicaland histopathological examinations. In addition to routine
      laboratory tests for liver function tests, Fas670 and Fas1377and FasL844 genetic
      polymorphisms of Fas/FasL promoter regions were assessed by RFLP-PCR (restriction
      fragmentlength polymorphism with polymerase chain reaction). Results: Significant
      higher levels of the AG genotype in Fas670and Fas1773 were observed in patients
      with cirrhosis and HCC (P=0.0001) as compared to control subjects. In
      addition,the CC genotype in FASL844 was also more common in patients (P=0.01).
      Furtehrmore, there was a significantassociation of substitution of A by G alleles
      in Fas670 and Fas1773 with advanced BCA staging (P=0.02, P=0.0001respectively)
      and larger tumor size >5cm (P=0.01, P=0.0001 respectively) and in Fas670 with
      advanced pathologicalgrading (P=0.0001). Moreover the CC genotype of FASL844 was
      significantly linked with advanced BCA, large tumorsize >5cm and advanced
      pathological grading (P=0.0001). Conclusion: The findings of the present study
      highlightassociations of genetic polymorphisms of promoter regions in Fas and Fas
      L with cirrhosis and HCC associated withchronic HCV. Support was also obtained
      for the conclusion that single nucleotide polymorphisms of the Fas/ FasLsystem
      impact on clinical and histopathological grading of HCCs. Further large scale
      studies are recommended forconfirmation.

PMID- 29072393
TI  - Tumor-Associated Neutrophils in Breast Cancer Subtypes
AB  - Background: Tumor associated neutrophils (TAN) are related to aggressiveness and
      a poor prognosis with humancancers. However, the relevance of TAN in breast
      cancer has not been previously investigated and here we sought todetermine their
      presence among different subtypes. Methods: We analyzed patients with stage I-III
      breast cancersbetween 2006 and 2012. Tumors were divided into three subtypes:
      hormone-receptor [ HR]-positive, HER2-negative(HR+,HER2-ve); HER2-positive and
      triple negative (TN). Hematoxylin and eosin stained sections were examinedand the
      number of TAN per 10 high power fields (HPF, 40x) was recorded. Tumors with >1
      TAN per 10 HPF wereconsidered TAN-positive. Fisher's exact test was used to test
      for independence between qualitative variables, andlogistic regression models
      were applied for multivariate analysis. Results: A total of 133 patients were
      assessed forinclusion and 105 were analyzed (28 excluded on various criteria).
      Some 72 tumors (69%) were classified as HR+,HER2-ve, 15 (14%) as HER2+ and 18
      (17%) as TN. Totals of 16 TN (88%), 8 HER2+ (53%) and 4 HR+, HER2-vetumors (5%)
      were TAN+ (p<0.001), including 79% of HR-ve tumors (19 of 24), in contrast to 11%
      of their HR+vecounterparts (9 of 81) (p<0.001). HER2 expression (p=0.023) and
      tumor grade (p<0.001) were also associated withTAN positivity. On multivariate
      analysis, only HR negativity (OR 16.85; 95% CI 4.4-64.6, p=<0.0001) was
      associatedwith a higher likelihood of TAN positivity. Conclusions: TAN are
      present in most TN tumors. We found an absence ofHR expression to be the only
      predictor of TAN positivity. These results raise the question as to whether TAN,
      as part ofthe tumor microenvironment, have a role in the aggressiveness and
      progression of TN tumors and thus warrant furtherinvestigation in this breast
      cancer subtype, particularly in relation to response to treatment and prognosis.

PMID- 29072394
TI  - Evaluation on Efficacy and Safety of Arsenic Trioxide Plus Transcatheter Arterial
      Chemoembolization Versus Transcatheter Arterial Chemoembolization alone
      forUnresectable Primary Liver Cancer
AB  - Currently, some clinical trials of arsenic trioxide (As203) plus transcatheter
      arterial chemoembolization (TACE)in the treatment of unresectable primary liver
      cancer (PLC) had been conducted, but the results were controversial.Therefore, we
      performed a meta-analysis on 14 clinical trials (1076 cases) to evaluate efficacy
      and safety of As203plus TACE versus TACE alone for unresectable PLC. The primary
      end points included objective response rate (ORR),karnofsky performance score
      (KPS) improvement rate, and 1-year survival rate. The second end points were
      adverseevents consisting of leukopenia, liver dysfunction, nausea/vomiting,
      fever, myelosuppression and pain. Our studyshowed that, compared with TACE alone,
      As203 plus TACE appeared a significant benefit on ORR (RR = 1.32, 95%
      CI:1.15,1.50, P < 0.0001), KPS improvement rate (RR = 1.24, 95% CI: 1.03,1.48, P
      = 0.02) and 1-year survival rate (RR =1.31, 95% CI: 1.15,1.49, P < 0.0001).
      Additionally, no remarkable difference of adverse events were observed betweentwo
      arms: leukopenia (RR = 1.44, 95% CI: 0.90,2.32, P = 0.13), liver dysfunction (RR
      = 0.96, 95% CI: 0.76,1.21, P= 0.71), nausea/vomiting (RR = 1.10, 95% CI:
      0.84,1.44, P = 0.48), fever (RR = 1.15, 95% CI: 0.82,1.61, P =
      0.43),myelosuppression (RR = 1.07, 95% CI: 0.74,1.56, P = 0.72) and pain (RR =
      0.88, 95% CI: 0.57,1.36, P = 0.57). Thisstudy demonstrated that As203 plus TACE
      produced a favorable efficacy without enhancing adverse events and was apromising
      combination therapy option for unresectable PLC.

PMID- 29072395
TI  - Pegfilgrastim Versus Filgrastim for Primary Prophylaxis of Febrile Neutropenia in
      Patients with non-Hodgkin'sLymphoma: A Cost-Effectiveness Study
AB  - Aim: One method to deal with febrile neutropenia is the use of granulocyte colony
      stimulating factors (G-CSFs).Pegfilgrastim or Filgrastim injection can lead to a
      reduction in febrile neutropenia and severe neutropenia in patientsreceiving
      chemotherapy. This study aimed to compare the cost-effectiveness of using
      Pegfilgrastim, 3-day Filgrastimand 1-day Filgrastim medication strategies for the
      primary prophylaxis of febrile neutropenia in patients with relapsednon-Hodgkin's
      lymphoma after salvage chemotherapy who referred to two referral centers
      affiliated to Iran, ShirazUniversity of Medical Sciences in 2014. Method: This
      cost-effectiveness study was conducted on 131 patients withnon-Hodgkin's
      lymphoma. The outcome of the study was the prevention of febrile neutropenia. The
      cost data werecollected from the health payer's perspective for each medication
      strategy by reviewing the patients' medical recordsand using expert opinion. The
      results were presented in terms of the incremental cost-effectiveness ratio
      (ICER) andthe sensitivity analysis was used to assess the robustness of results.
      In this study, the collected data were analyzedusing Excel 2007 and Tree-age
      2011. Results: The results showed that the degrees of febrile neutropenia
      prevented byPegfilgrastim, 3-day Filgrastim and 1-day Filgrastim strategies were
      0.97, 0.95 and 0.83, respectively, and the averageannual costs of hospitalization
      per patient were, 5299, 4959 and 5808 PPP$. Conclusion: The results showed
      thatwhile 1-day Filgrastim was absolutely predominant, using the 3-day Filgrastim
      and Pegfilgrastim strategies were morecost-effective. Therefore, they can be
      recommended respectively as the first and second treatment priorities in
      patientswith non-Hodgkin's lymphoma after salvage chemotherapy.

PMID- 29072396
TI  - Bayesian Inference on Malignant Breast Cancer in Nigeria: A Diagnosis of MCMC
      Convergence
AB  - Background: There has been no previous study to classify malignant breast tumor
      in details based on Markov ChainMonte Carlo (MCMC) convergence in Western,
      Nigeria. This study therefore aims to profile patients living with benignand
      malignant breast tumor in two different hospitals among women of Western Nigeria,
      with a focus on prognosticfactors and MCMC convergence. Materials and Methods: A
      hospital-based record was used to identify prognosticfactors for malignant breast
      cancer among women of Western Nigeria. This paper describes Bayesian inference
      anddemonstrates its usage to estimation of parameters of the logistic regression
      via Markov Chain Monte Carlo (MCMC)algorithm. The result of the Bayesian approach
      is compared with the classical statistics. Results: The mean age of
      therespondents was 42.2 +/-16.6 years with 52% of the women aged between 35-49
      years. The results of both techniquessuggest that age and women with at least
      high school education have a significantly higher risk of being diagnosed
      withmalignant breast tumors than benign breast tumors. The results also indicate
      a reduction of standard errors is associatedwith the coefficients obtained from
      the Bayesian approach. In addition, simulation result reveal that women with
      atleast high school are 1.3 times more at risk of having malignant breast lesion
      in western Nigeria compared to benignbreast lesion. Conclusion: We concluded that
      more efforts are required towards creating awareness and advocacycampaigns on how
      the prevalence of malignant breast lesions can be reduced, especially among
      women. The applicationof Bayesian produces precise estimates for modeling
      malignant breast cancer.

PMID- 29072397
TI  - The DNA Methyltransferase 3B -149 Genetic Polymorphism Modulates Lung Cancer Risk
      from Smoking
AB  - Background: Smoking can cause increase of DNA methylation and hypermethylation of
      tumor suppressor genes,this possible contributing to subsequent lung cancer
      development. DNA methyltransferase 3B (DNMT3B) is crucialin regulation of DNA
      methylation and it has been proposed that green tea might lower cancer risk
      through inhibitingits activity. Here, we designed a case-control study to
      investigate whether the DNMT3B -149 genetic polymorphismcould modulate lung
      cancer risk due to smoking. Possible interactions of smoking and green tea
      consumption with thisDNMT3B genetic polymorphism were also assessed. Materials
      and Methods: A total of 190 lung cancer patients and380 healthy controls were
      recruited. Questionnaires were administered to obtain data on sociodemographic
      and lifestylevariables, as well as family history of lung cancer. Genotypes for
      DNMT3B -149 were identified by polymerase chainreaction. Results: Smoking, green
      tea consumption, exposure to cooking fumes, family history of lung cancer, andthe
      DNMT3B -149 genotype (odds ratio (OR)=2.65; 95% confidence interval (CI) 1.15
      6.10) were all significantlyassociated with the development of lung cancer.
      Smokers carrying the DNMT3B -149 TT genotype were at elevatedrisk compared to non
      smokers carrying DNMT3B -149 (OR=7.69; 95% CI 2.55-23.14). Interaction of smoking
      withDNMT3B -149 genotypes was significant regarding lung cancer risk. However,
      interaction between green tea drinkingand DNMT3B -149 genotypes was not.
      Conclusions: The DNMT3B -149 TT genotype might increase the smokingassociatedlung
      cancer risk.

PMID- 29072398
TI  - Quantitative Analysis of Intracellular Motility Based on Optical Flow Model
AB  - Analysis of cell mobility is a key issue for abnormality identification and
      classification in cell biology research. However, since cell deformation induced
      by various biological processes is random and cell protrusion is irregular, it is
      difficult to measure cell morphology and motility in microscopic images. To
      address this dilemma, we propose an improved variation optical flow model for
      quantitative analysis of intracellular motility, which not only extracts
      intracellular motion fields effectively but also deals with optical flow
      computation problem at the border by taking advantages of the formulation based
      on L1 and L2 norm, respectively. In the energy functional of our proposed optical
      flow model, the data term is in the form of L2 norm; the smoothness of the data
      changes with regional features through an adaptive parameter, using L1 norm near
      the edge of the cell and L2 norm away from the edge. We further extract
      histograms of oriented optical flow (HOOF) after optical flow field of
      intracellular motion is computed. Then distances of different HOOFs are
      calculated as the intracellular motion features to grade the intracellular
      motion. Experimental results show that the features extracted from HOOFs provide
      new insights into the relationship between the cell motility and the special
      pathological conditions.

PMID- 29072399
TI  - Free Radical Scavenging Properties of Annona squamosa
AB  - Annona squamosa has extensively been used in the traditional and folkloric
      medicine and found to possess manybiological activities. Different solvents,
      petroleum ether, chloroform, ethyl acetate and methanol extracts of
      Annonasquamosa seeds (ASPE, ASCH, ASEA, ASME) have been used to prepare plant
      extracts. The present investigationsdealt with the free radical scavenging
      activity of four extracts using various techniques such as total reducing
      powerestimation, total phenolic count, 1,1-diphenyl-2-picryl hydrazyl (DPPH)
      radical scavenging effect, evaluation of ABTScation decolorisation capacity, FRAP
      assay, hdroxyl radical scavenging assay, super oxide assay and Nitric oxide
      radicalscavenging assay of the extracts. The results showed that the four
      extracts of Annona squamosa showed significantreducing power in four extracts.
      The total phenolic contents in petroleum ether, chloroform, ethyl acetate,
      methanolextracts and positive control were 0.64+/-0.17, 0.54+/-0.27, 0.49+/-0.24,
      0.57+/-0.22 and 0.66+/-0.33. The antioxidant capacity byABTS assay of ASPE, ASCH,
      ASEA, ASME and positive control, trolox showed 77.75+/-0.5,73.25+/-1.7,78.5+/-
      1.2 , 80 +/- 0.8MUg/ml and 94.2 +/- 0.9 respectively. The (50 % scavenging
      activity) SA50 of ASPE and ASCH, ASEA and ASME wasfound to be 34.4 MUg/ml, 43.8
      MUg/ml 34.7 MUg/m and 28.8 MUg/ml respectively by DPPH assay. The percentage
      ofhydroxyl radical scavenging increased with the increasing concentration of the
      extracts. ASPE, ASCH, ASEA andASME showed superoxide radical scavenging activity,
      as indicated by their values 66 +/- 0.5, 68 +/- 1 ,63 +/- 1 and 70 +/-0.5 MUg/ml
      respectively compared to gallic acid which was 97 +/- 0.5 MUg/ml. The values for
      scavenging of nitric oxidefor ASPE, ASCH, ASEA and ASME were 91.0 +/- 1.0, 66.75
      +/- 0.5, 71.75 +/- 1.1 and 75.75 +/- 1.15 MUg/ml while value forstandard ascorbic
      acid was 91.0 +/- 1.0 MUg/ml. The results revealed strong antioxidants in four
      extracts may lead to thedevelopment of potent antioxidant agents from Annona
      squamosa seeds.

PMID- 29072400
TI  - Inertial Sensor-Based Motion Analysis of Lower Limbs for Rehabilitation
      Treatments
AB  - The hemiplegic rehabilitation state diagnosing performed by therapists can be
      biased due to their subjective experience, which may deteriorate the
      rehabilitation effect. In order to improve this situation, a quantitative
      evaluation is proposed. Though many motion analysis systems are available, they
      are too complicated for practical application by therapists. In this paper, a
      method for detecting the motion of human lower limbs including all degrees of
      freedom (DOFs) via the inertial sensors is proposed, which permits analyzing the
      patient's motion ability. This method is applicable to arbitrary walking
      directions and tracks of persons under study, and its results are unbiased, as
      compared to therapist qualitative estimations. Using the simplified mathematical
      model of a human body, the rotation angles for each lower limb joint are
      calculated from the input signals acquired by the inertial sensors. Finally, the
      rotation angle versus joint displacement curves are constructed, and the
      estimated values of joint motion angle and motion ability are obtained. The
      experimental verification of the proposed motion detection and analysis method
      was performed, which proved that it can efficiently detect the differences
      between motion behaviors of disabled and healthy persons and provide a reliable
      quantitative evaluation of the rehabilitation state.

PMID- 29072401
TI  - Colorectal Cancer Incidence Trend and Projections in Tunisia (1994 - 2024)
AB  - Objectives: The aim of this study was to describe trends of colorectal cancer
      incidence during the period 1994-2009and to generate projections until 2024.
      Methods: The North-Tunisia Cancer Registry (NTCR) was the source of data
      forpatients with CRC. This registry lists, since 1994, cases of malignant tumors
      in people living in North Tunisia, includingthe District of Tunis, the north east
      and the north west. Cases were classified using the International
      Classificationof Diseases for Oncology. Data were analyzed using R software and
      Joinpoint one was employed to analyse trends.Projections were performed using the
      Age Period Cohort based on poisson regression. Results: During the period 1994to
      2009, 6,909 new cases of CRC were registered in Northern Tunisia. The age
      standardized incidence rate (ASR)increased significantly from 6.4/100,000 in 1994
      to 12.4/100,000 in 2009. Trends in CRC incidence was significantlyrising with an
      annual percentage change (APC) of + 3,9% [2.8% -5.1%]. Without effective
      interventions, the predictedCRC ASR would be 39.3/100,000 [CI 95%: 32,9/100,000 -
      48,8/100,000] in 2024. Conclusion: The incidence ofcolorectal cancer is clearly
      increasing in Tunisia. Strengthening of screening and primary prevention measures
      is tobe recommended.

PMID- 29072402
TI  - Outcomes of High Risk Patients with Febrile Neutropenia at a Tertiary Care Center
AB  - Fever during chemotherapy-induced neutropenia continues to be a major cause of
      morbidity and mortality incancer patients. Mortality depends on the duration and
      degree of neutropenia, bacteremia, sepsis, performance status,comorbidities and
      other parameters. The highest mortality rates in cancer patients hospitalized
      with febrile neutropenia(FN) are observed in those with documented infection. The
      objectives of the study were to present available tools forrisk assessment, to
      review pathogens causing infections in adult FN patients and to assess outcomes.
      Methods: Thiscross sectional study was conducted on adult culture positive FN
      patients admitted to the Hematology/Oncologyservice at the Aga Khan University
      Hospital, Karachi, Pakistan from 1st January 2009 to 31st December 2012.
      Highriskcriteria were defined as profound neutropenia, short latency from a
      previous chemotherapy cycle, sepsis orclinically documented infection at
      presentation, severe co-morbidity and a performance status greater than or
      equalto 3. All types of organisms in blood culture and the outcomes of the
      patients were recorded on Proforma. Results:A total of 156 patients with culture
      positive febrile neutropenia were identified during the study period. The meanage
      was 47 years with a slight male predominance of 54%. One hundred and sixteen
      patients fulfilled the criteria forthe high risk group. Fifty two percent had a
      single high risk factor and 40 % had two. All patients harbored eithersingle or
      multiple bacterial organisms including gram positive, gram negative or both
      types. Some 34% of patientshad gram positive bacteremia, 57 % had gram negative
      and 9 % were infected with both. Among 73 gram positivecultures 44 % were
      Staphylococcus species and among 123 gram negative cultures 43 % were E. coli.
      One hundredand fifteen patients recovered uneventfully and could be discharged.
      Thirty two patients in the high risk and 9 in thelow risk groups deceased with an
      overall mortality of 26 %. The mean hospital stays of patients with solid tumors
      andhematological malignancies were 7.58 and 15.0 days, respectively. Mortality
      was higher in the latter group, and alsoin high risk patients with both gram
      positive and negative bacteremia. Conclusion: We emphasize the importance ofrisk
      stratification and continuous surveillance of the spectrum of locally prevalent
      pathogens and their susceptibilitypatterns for formulation of therapeutic
      regimens for febrile neutropenic patients.

PMID- 29072403
TI  - Inconsistencies of Breast Cancer Risk Factors between the Northern and Southern
      Regions of Vietnam
AB  - Background: In recent decades the amount of new breast cancer cases in the
      southern region has been reportedto increase more rapidly than in the
      northernVietnam. The aim of this study is to compare breast cancer risk
      factorsbetween the two regions and establish if westernized influences have an
      impact on any reported differences. Method:Data was collected from the two
      largest oncology hospitals in the north and the south of Vietnam in 2015. Breast
      density,demographic, reproductive and lifestyle data of 127 cases and 269
      controls were collected in the north and 141 casesand 250 controls were gathered
      from the south. Baseline differences in factors between cases and age-matched
      controlsin each region were assessed using chi-square tests and independent t
      tests. Odds ratios (OR) for independent riskfactors for breast cancer were
      obtained from conditional logistic regression. Results: In northern Vietnam
      significantlyincreased risks in developing breast cancer were observed for women
      with age at first menstrual period less than 14years old (OR=2.1; P<0.05), post
      menopausal status (OR=2.6; P<0.0001), having less than 2 babies (OR=2.1;
      P<0.05).Southern Vietnamese women having a breast density of more than 75%
      (OR=2.1; P<0.01), experiencing post-menopause(OR=1.6; P<0.05), having a history
      of less than 3 pregnancies (OR=2.6; P<0.0001) and drinking more than a cup
      ofcoffee per day (OR=1.9; P<0.05) were more likely to be diagnosed with breast
      cancer. Conclusion: We found thatwomen living in the south had some breast cancer
      associations, such as increased mammographic density and coffeeconsumption, which
      are closer to the risks in westernized populations than women in the north.

PMID- 29072404
TI  - Knowledge and Perceptions of Common Breast Cancer Risk Factors in Northern Saudi
      Arabia
AB  - Background: Breast cancer is the second leading cause of cancer death in women
      around the world. The degreeof adoption of a preventive lifestyle offers valuable
      information for planning appropriate intervention programs forimproving women's
      health. The objective of the present study was to assess the levels of breast
      cancer related knowledgeamong a Northern Saudi population. Methodology: In this
      cross sectional study, data were obtained from 566 Saudivolunteers living in the
      city of Hail, the Kingdom of Saudi Arabia (KSA). Results: With regard to breast
      cancer riskfactors, 427/566 (75.4%) of participants answered in the affirmative
      to whether breast cancer could be inherited. Forearly puberty and late menopause,
      209/566 (37%) were in agreement with increased risk, for low and delayed
      childbirth, 261/566 (46%), and for overweight and obesity, 210/566(37%). For the
      question of whether natural breast feedingcan reduce the risk of breast cancer,
      only 35/566 (6.2%) said yes. Conclusion: There is a general lack of
      knowledgeregarding several BC risk factors among the northern Saudi community
      which necessitates urgent implementation ofeducational programs.

PMID- 29072406
TI  - Mentor Health.

PMID- 29072405
TI  - Factors Associated with a Lack of Knowledge of Performing Breast Self-Examination
      and Unawareness of Cervical Cancer Screening Services: Evidence from the 2015
      Egypt Health Issues Survey
AB  - Background: The incidence of breast and cervical cancers is growing rapidly among
      Egyptian women. In thiscontext, we assessed the prevalence of, and factors
      associated with the lack of knowledge among Egyptian females ofperforming breast
      self-examination (BSE) and unawareness of cervical smear cancer screening
      services. Methods:Secondary data analysis was performed on a representative
      population-based sample of 7,518 Egyptian females aged15-59 years from the 2015
      Egypt Health Issues Survey (EHIS). Crude and adjusted odds ratios (aOR) were used
      toexplore the relationship between sociodemographic variables and having a lack
      of knowledge of performing BSE orunaware of cervical smear cancer screening
      service amongst 6,572 and 6,942 Egyptian females aged 21-59 years,respectively.
      Results: Mean age of females was 36.9 years with 62% aged between 21-39 years.
      The proportion ofwomen with a lack of knowledge of performing BSE or who were
      unaware of cervical smear cancer screening servicewas 87.4% and 92.3%,
      respectively. After adjusting for potential confounding of sociodemographic and
      obstetriccharacteristics, young women aged 21-29 years (P<0.001), primary
      education or below (P<0.001), residing in ruralareas (aOR, 1.37 and 1.48,
      P=0.001), accessing different media outlets "not at all or less than once a week"
      (aOR, 2.81and 1.46, P<=0.05), were associated with a greater likelihood of being
      with lack knowledge of performing BSE or beingunaware of cervical smear cancer
      screening services. Conclusions: In a country burdened with breast and
      cervicalcancers, the majority of Egyptian women have a lack of knowledge on how
      to perform BSE or were unaware of theavailable cervical smear cancer screening
      services. Robust health campaigns are warranted to raise public knowledgeof the
      method of BSE and of cervical smear cancer screening services, especially amongst
      females aged less than 30years, with low levels of education, or those living in
      rural areas.

PMID- 29072407
TI  - Systemic Conditions and Oral Health.

PMID- 29072409
TI  - Ethical Priming.

PMID- 29072410
TI  - OSA Causes Complications in Dental Implants.

PMID- 29072408
TI  - Knowledge Attitude and Practice of Colorectal Cancer among School Teachers in Al
      Ahsa Saudi Arabia
AB  - Background: Colorectal cancer is the second leading cause of deaths among cancers
      affecting both men and womenin the United States. Annually, about 140,000
      Americans are diagnosed with colorectal cancer, and more than 50,000people die
      from it. In Saudi Arabia, this cancer ranks first among men and third among
      women. Nevertheless, this typeof cancer is one of the most preventable types of
      cancer. Objective: The aim of this study was to assess the level ofcolorectal
      cancer awareness among teaching staff (educators) in Al-Ahsa, Saudi Arabia.
      Methodology: The currentcross-sectional study was conducted in teaching staff in
      Al-Ahsa, Eastern province, Saudi Arabia, from February 2017to May 2017. A self
      administered questionnaire was used for data collection and SPSS (version 24) was
      run for dataanalysis. Result: A total of 367 teachers (165 males and 202 females)
      were recruited for the present investigation. Theparticipants aged from 25 to 55
      years and most of them were married (87%). The majority had inadequate
      knowledgeabout risk factors of colon cancer. No significant difference was
      observed between people living in urban and ruralareas regarding knowledge of
      risk factors for colorectal cancer (p>=0.05). Concerning colorectal cancer
      screening tests,39% of men and 42% of women were unaware ; although, 12.8% of the
      participants reported a positive family historyof colon cancer. In General,
      participants with higher education level had higher level of awareness on colon
      cancer.Conclusions: The findings of this study demonstrated that most of
      educators, including men and women are unawareof colon cancer risk factor.
      Furthermore, their knowledge of colon cancer signs, symptoms, and screening
      methods wereinadequate. With respect to our findings, enhancement of colon cancer
      knowledge among educators is recommendedusing health education campaign in Al
      Ahsa.

PMID- 29072412
TI  - Friends, Family Play Crucial Roles in Oral Health Care.

PMID- 29072411
TI  - Survey of Cancer Patient Safety Culture: A Comparison of Chemotherapy and
      Oncology Departments of Teaching Hospitals of Tehran
AB  - Background: Patient safety culture plays an important role in healthcare systems,
      especially in chemotherapy andoncology departments (CODs), and its assessment can
      help to improve quality of services and hospital care. Objective:This study aimed
      to evaluate and compare items and dimensions of patient safety culture in the
      CODs of selected teachinghospitals of Iran and Tehran University of Medical
      Sciences. Materials and Methods: This descriptive-analytical crosssectionalsurvey
      was conducted during a six-month period on 270 people from chemotherapy and
      oncology departmentsselected through a cluster sampling method. All participants
      answered the standard questionnaire for "Hospital Survey ofPatient Safety
      Culture" (HSOPSC). Statistical analyses were performed using SPSS/18 software.
      Results: The averagescore for patient safety culture was three for the majority
      of the studied CODs. Statistically significant differences wereobserved for
      supervisor actions, teamwork within various units, feedback and communications
      about errors, and the levelof hospital management support. (p<0.05).
      Relationships between studied hospitals and patient safety culture were
      notstatistically significant (p>0.05). Conclusion: Our results showed that the
      overall status of patient safety culture is notgood in the studied CODs. In
      particular, teamwork across different units and organizational learning with
      continuousimprovement were the only two properly operating items among 12
      dimensions of patient safety culture. Therefore,systematic interventions are
      strongly required to promote communication.

PMID- 29072414
TI  - Synthetic Tooth Enamel May Lead to More Resilient Structures.

PMID- 29072413
TI  - p16 Tumor Suppressor Gene Methylation in Diffuse Large B Cell Lymphoma: A Study
      of 88 Cases at Two Hospitals in the East Coast of Malaysia
AB  - Introduction: p16 gene plays an important role in the normal cell cycle
      regulation. Methylation of p16 hasbeen reported to be one of the epigenetic
      events contributing to the pathogenesis of diffuse large B-cell lymphoma(DLBCL)
      which occurring at varying frequency. DLBCL is an aggressive and high-grade
      malignancy which accountsfor approximately 30% of all non-Hodgkin lymphoma cases.
      However, little is known regarding the epigeneticalterations of p16 gene in DLBCL
      cases in Malaysia. Therefore, the objective of this study was to examine the
      statusof p16 methylation in DLBCL. Methods: A total of 88 formalin-fixed paraffin
      embedded DLBCL tissues retrievedfrom two hospitals located in the east coast of
      Malaysia, namely Hospital Tengku Ampuan Afzan (HTAA) Pahang andHospital
      Universiti Sains Malaysia (HUSM) Kelantan, were chosen for this study. DNA
      specimens were isolated andsubsequently subjected to bisulfite treatment prior to
      methylation specific-PCR. Two pairs of primers were used toamplify methylated and
      unmethylated regions of p16 gene. The PCR products were then separated using
      agarose gelelectrophoresis and visualised under UV illumination. SPSS version
      12.0 was utilised to perform all statistical analysis.Result: p16 methylation was
      detected in 65 of 88 (74%) samples. There was a significant association between
      p16methylation status and patients aged >50 years old (p=0.04). Conclusion: Our
      study demonstrated that methylation ofp16 tumor suppressor gene in our DLBCL
      cases is common and significantly increased among patients aged 50 yearsand
      above. Aging is known to be an important risk factor in the development of
      cancers and we speculate that thismight be due to the increased transformation of
      malignant cells in aging cell population. However, this has yet to beconfirmed
      with further research and correlate the findings with clinicopathological
      parameters.

PMID- 29072415
TI  - Impact of a Stress Management Intervention Program on Sexual Functioning and
      Stress Reduction in Women with Breast Cancer
AB  - Breast cancer as the most common cancer among women endangers various aspects of
      their sexual lives and is amajor culprit regarding health impairment and low life
      quality. The aim of this study was to examine the effect of a stressmanagement
      intervention program on sexual functioning and stress reduction in women with
      breast cancer. This studyemployed a quasi-experimental pre-test, post-test design
      which included follow-up checks and a control group. To thisend, 104 women with
      breast cancer referring to Hamadan's Mahdiyeh MRI Center at the time of data
      collection wereconventionally selected in 2015. Using permuted blocks, they were
      randomly divided into experimental and controlgroups (n= 52), only the former
      receiving stress management counseling for 18 hours. Data were collected through
      ademographic questionnaire, the Female Sexual Function Index (FSFI)
      questionnaire, and Harry's stress questionnaire,filled out by patients before and
      after the intervention. To analyze the data, descriptive statistics and two-way
      ANOVAwere used. The results showed that cognitive - behavioral stress management
      group therapy improved total sexualfunctioning and its subscales. After the
      treatment, there was a significant difference in mean scores between the
      groups(p=0.01). Moreover, significant differences were observed in the mean
      scores for stress with improvement in theexperimental group in post-test results.
      Cognitive - behavioral group therapy for stress management was thuis foundto
      improve total sexual functioning and its subscales and reduce the level of stress
      in the experimental group after theintervention and follow-up period with an
      interval of two weeks. Therefore, this method can be used as a
      complementarytherapy along with medical treatment in oncology centers.

PMID- 29072416
TI  - Novel IRF-1 Mutations in a Small Cohort of Leukaemia Patients From Saudi Arabia
AB  - Involvement of the Interferon Regulatory Factor 1 (IRF-1) gene in regulation of
      cell differentiation and proliferationmade it a potential target in cancer
      research. IRF-1 acts as a tumor suppressor gene, and is inactivated in
      chronic(CML) and non-chronic myelogenous leukemia (non-CML). In the light of
      numerous reports on genetic changes in thenoncoding region of the IRF-1 gene,
      this study aimed to explore possible genomic changes in coding and non
      codingregions of IRF-1 in a random sample of leukemic Saudi patients, in order to
      obtain insights into potential impact ofgenetic changes on clinicopathological
      characteristics. Patients were classified into two major leukemia subtypes: CML(8
      cases; 36.4%) and non-CML (14 cases; 63.6%). Sequencing results revealed two
      novel mutations in the coding areaof the IRF-1 gene likely to influence the IRF
      1/DNA binding affinity. In addition, three mutational sites in the
      noncodingregion between exon 5&6 (8985(T>G), 8,990(T>G) and 8995(A>G) were
      identified. In conclusion, a largerrepresentative study might help provide better
      understanding of the possible contribution of the identified geneticchanges in
      IRF-1 to disease prognosis and outcomes in leukemic patients.

PMID- 29072417
TI  - Prediction of Response to Irinotecan and Drug Toxicity Based on Pharmacogenomics
      Test: A Prospective Case Study in Advanced Colorectal Cancer
AB  - Background: FOLFIRI regimen, which is composed of 5-FU, Leucovorin, and
      Irinotecan, is used in the first-linechemotherapy of metastatic colorectal
      cancer. Irinotecan life threatening toxicity is partly related to cytotoxic
      drugmetabolite which is primarily inactivated by the UGT1A1 enzyme. The primary
      aim of the present research was tofind the correlation between UGT1A1-genotype
      and clinical toxicity of irinotecan. Methods: In a prospective studyfrom March
      2011 to December 2013, all patients with metastatic colorectal cancer who had
      been referred to MedicalOncology Department of Iran Cancer Institute were
      genotyped for UGT1A1*28 before the first cycle of chemotherapy.All of the
      patients signed informed consent and trial approved by Ethics Committee of the
      Tehran University ofMedical Sciences. Reduction of the standard dose of
      Irinotecan (180 mg/m2 body surface area) was measured basedon NCI toxicity
      criteria after the first cycle of chemotherapy. Patients with previous treatment
      with Oxaliplatin andfluorouracil (5-FU) in the adjuvant setting and adequate
      liver, kidney, and heart function were included in the trial. Bothsynchronous and
      metachronous metastatic disease were noticeable. Results: A total of 50 patients
      with median age of52 years were included. Most (70%) of the patients had more
      than one site of metastases in peritoneum, liver, and/orlung. Thirty-one patients
      had UGT1A1*1 normal genotype, 13 were in heterozygote and 6 were in homozygote
      stateofUGT1A1*28/*28. A clinically relevant increase in early toxicity was found
      in patients carrying the UGT1A1*28/*28genotype with odds Ratio (OR) of 2.6 (95%CI
      2.5-27.28). Similarly, there was a trend of lower overall survival inhomozygote
      group with an HR (Hazardous Ratio) of 2.76 (95%CI .88-.61). No statistically
      significant relationship wasfound between UGT1A1genotypes and response to
      therapy. Conclusions: UGT1A1 28*/28* is strongly associatedwith drug's life
      threatening toxicity even in a moderate dose of Irinotecan. On the other hand,
      UGT1A1 genotype datawas not helpful to differentiate response to treatment.

PMID- 29072418
TI  - Colitis-associated colorectal cancer in patients with inflammatory bowel disease.
AB  - Colitis-associated colorectal cancer (CACRC) is a major concern in patients with
      long-standing inflammatory bowel disease (IBD). CACRC can develop under the
      influence of several risk factors including longer duration and disease extent
      and shows clinical and molecular features different from those of sporadic CRC.
      Several academic societies have recommended surveillance guidelines for CACRC
      that develops in IBD patients. Patients are stratified according to risk for CRC
      and differentiated by surveillance colonoscopy and management. In the current
      article, we review CACRC in IBD patients generally and introduce future
      directions.

PMID- 29072419
TI  - Endoscopic treatment of obesity and complications after bariatric surgery.
AB  - Prevalence and incidence of obesity in the population has been increasing for
      decades. Due to associated comorbidities, treatment of obesity has become a
      global health topic and should be addressed with multimodal strategies. As
      conservative treatment has high rates of failure, bariatric surgery is often
      performed, especially in cases of severe obesity. However, interventional
      endoscopic options are gaining importance as less invasive approach. Intragastric
      balloons and duodenojejunal bypass liners are the most frequent applied
      endoscopic therapies. Besides primary bariatric intervention, endoscopy may also
      help bridging towards surgery. Management of postsurgical adverse events (e.g.
      leakage, stenosis) can be handled endoscopically as well. This article summarizes
      current knowledge and available endoscopic treatment options for obesity.

PMID- 29072420
TI  - 3D-laparoscopic anterior rectal resection in a patient with crossed fused renal
      ectopia: the importance of 3D imaging.

PMID- 29072422
TI  - Study Links Changes in Oral Microbiome with Dental Disease.

PMID- 29072423
TI  - The Oral Effects of Inhalation Corticosteroid Therapy: An Update.
AB  - Inhaled corticosteroids (IC) are commonly used for the treatment ofrespiratory
      diseases. Although these medications are generally considered safer whencompared
      to oral systemic corticosteroids, there is evidence for potential systemicand
      local adverse effects with their use. Therefore, dentists should be aware of
      theseadverse effects, especially the commonest local effects that can involve the
      oralmucosa. This article reviews the literature on the complications of IC
      therapy withemphasis on its potential oral effects.

PMID- 29072421
TI  - Anxiety, Depression and Quality of Life in Breast Cancer Patients in the Levant
AB  - Background: Limited data are currently available regarding the psychological well
      being and quality of life ofbreast cancer patients after active treatment in
      Lebanon and the Arab region in general. The objective of this study wasto
      determine the prevalence of anxiety and depression among Arab breast cancer
      patients and assess the quality of lifewith reference to socio-demographic and
      clinical characteristics. Methods: This cross-sectional study was conductedamong
      female breast cancer patients diagnosed between January 2009 and March 2014, who
      were recruited from theoutpatient clinics of Naef K. Basile Cancer Institute at
      the American University of Beirut Medical Center (AUBMC)from November 2015 till
      December 2016. An interview was conducted utilizing two validated questionnaires:
      theHospital Anxiety and Depression Scale (HADS) and the Functional Assessment of
      Cancer Therapy-Breast (FACT-B).Socio-demographic and clinical characteristics
      that might predict patient quality of life were collected and summarized.Results:
      A total of 150 patients were interviewed (median age 53.5+/-10.4 years). Most
      were assessed 3 to 5 years (68.7%)after initial diagnosis and had undergone
      surgery, chemotherapy, radiation, or hormonal therapy (97.3%, 79.3%, 80.7%and
      86.0%, respectively). The median total HADS score was 10.0 +/- 8.0, with
      approximately 41.3% of study participantshaving abnormal scores on the anxiety
      subscale and 24.7% on the depression subscale. Significant predictors of
      totalHADS score were nationality and level of education (p=0.001, p=0.001
      respectively; R2=0.181). Participants who wereIraqi, had stage IV disease, had a
      household monthly income below 1000 USD, or had received chemotherapy
      exhibitedsignificantly lower total FACT-B scores, these being highly negatively
      correlated with total HADS scores (rs= -0.73,p=0.001). Conclusion: There is a
      vital need for the development of individualized interventions and
      psychosocialsupport programs tailored to the physical and psychological well
      being of breast cancer patients in the Levant region.

PMID- 29072425
TI  - A Numerical Investigation into the Effects of Overweight and Obesity on Total
      Knee Arthroplasty
AB  - Overweight and obesity increase risks of knee osteoarthritis, which is a major
      cause of disability. Severe knee osteoarthritis can be treated by knee
      arthroplasty. Total knee arthroplasty has been used in overweight and obese
      patients; however, clinical reports showed that the outcome of this group of
      patients was not good as normal-weight patients. Two computer models were created
      in this paper to simulate the effect of excess loads on the distal femoral bone
      and contact pressures in total knee arthroplasty during a gait cycle. The
      numerical results showed increased stress in periprosthetic distal femoral bones
      and higher contact pressure on tibial polyethylene insert during the stance
      phase. Based on the computer simulation results and published research work,
      cementless total knee arthroplasty with thicker tibial polyethylene insert may be
      a better option for overweight patients.

PMID- 29072424
TI  - Prognostic Factors of Adrenocortical Carcinoma: An Analysis of the Surveillance
      Epidemiology and End Results (SEER) Database
AB  - Objective: To define the prognostic factors associated with overall survival (OS)
      and cancer-specific survival (CSS)for adrenocortical carcinoma (ACC). Patients
      and Methods: We used the Surveillance, Epidemiology and End Results(SEER)
      database (1973-2014) to identify ACC patients. Correlated variables, including
      age, sex, race, tumor laterality,marital status at diagnosis, treatment of
      primary site, lymph node dissection, radiation therapy, chemotherapy, tumorsize
      and tumor stage, were extracted. Univariate and multivariate Cox regression were
      used to define the prognosticfactors. Harrell's concordance index (C index) was
      calculated to evaluate the discrimination ability for the prognosticpredictive
      models. Results: There were 749 ACC patients identified from the database. The
      overall median survivaltime was 22 (95%CI, 18-25) months. In multivariate
      analysis, age, treatment, chemotherapy and tumor stage wereindependent risk
      factors for both overall and cancer-specific survival. Tumor stage had a dominant
      effect on the cancerprognosis. Additionally, the ENSAT stage had better
      discrimination than the AJCC stage group in different predictivemodels.
      Conclusion: Our study shows that age, treatment of primary site, chemotherapy and
      tumor stage were prognosticfactors for overall and cancer-specific mortality in
      ACC patients. Among these factors, tumor stage had a dominanteffect. The ENSAT
      stage was more discriminative than the 7th AJCC stage group. Further multi-center
      prospectivevalidation is still needed to confirm these outcomes.

PMID- 29072426
TI  - Traumatically Intruded Permanent Teeth: Three Case Reports and a Review of
      Current Recommendations.
AB  - Intrusion of permanent teeth is not extensively covered in theliterature compared
      to other injuries. Treatment guidelines have been publishedand clinical data is
      accumulating to support the current recommendations, whichare illustrated in the
      three cases here. This review evaluates the current informationabout management
      of traumatically intruded permanent teeth. As more dataaccumulates, uncertainties
      with respect to both treatment recommendations andlong-term outcomes can be
      expected to be elucidated.

PMID- 29072427
TI  - Antibiotic Resistance and Good Stewardship.
AB  - This article examines dentistry's role in managing the antibiotic resistance
      problem through a more appropriate use of antibiotics.

PMID- 29072429
TI  - Well-Stocked Emergency Medical Kits Can Help Mitigate Risk.

PMID- 29072428
TI  - Long-Term Disease-Free Survival of Non-Metastatic Breast Cancer Patients in Iran:
      A Survival Model with Competing Risks Taking Cure Fraction and Frailty into
      Account
AB  - Introduction: Survival modeling is a very important tool to detect risk factors
      and provide a basis for health careplanning. However, cancer data may have
      properties leading to distorted results with routine methods. Therefore,
      thisstudy aimed to cover specific factors (competing risk, cure fraction and
      heterogeneity) with a real dataset of Iranianbreast cancer patients using a
      competing risk-cure-frailty model. Materials and methods: For this historical
      cohortstudy, information for 550 Iranian breast cancer patients who underwent
      surgery for tumor removal from 2001 to 2007and were followed up to March 2017,
      was analyzed using R 3.2 software. Results: In contrast to T-stage and N
      stage,hormone receptor status did not have any significant effect on the cure
      fraction (long-term disease-free survival).However, T-stage, N-stage and hormone
      receptor status all had a significant effect on short-term disease-free
      survivalso that the hazard of loco-regional relapse or distant metastasis in
      cases positive for a hormone receptor was only 0.3times that for their negative
      hormone receptor counterparts. The likelihood of locoregional relapse in the
      first quartileof follow up was nearly twice that of other quartiles. The least
      cumulative incidence of time to locoregional relapse wasfor cases with a positive
      hormone receptor, low N stage and low T stage. The effect of frailty term was
      significant inthis study and a model with frailty appeared more appropriate than
      a model without, based on the Akaike informationcriterion (AIC); values for the
      frailty model and one without the frailty parameter were 1370.39 and 1381.46,
      respectively.Conclusions: The data from this study indicate ae necessity to
      consider competing risk, cure fraction and heterogeneityin survival modeling. The
      competing risk-cure-frailty model can cover complex situations with survival
      data.

PMID- 29072430
TI  - Educational Intervention on Breast Self-Examination Behavior in Women Referred to
      Health Centers: Application of Health Belief Model
AB  - Introduction and aims: Screening can play a major role in reducing deaths
      associated with cancer. Breast selfexamination(BSE) is a cheap, non-complicated
      and non-invasive method for breast cancer screening. This study aimedto examine
      the effects of an educational intervention based on the health belief model (HBM)
      on BSE behavior in womenreferred to health centers in Fasa, Iran. Methods: This
      quasi-experimental study was conducted on 92 women, dividedinto an experimental
      and a control group. Data were collected using a validated questionnaire covering
      demographiccharacteristics, knowledge, HBM constructs and breast self-examination
      performance. An educational program wasperformed in five sessions through group
      discussion with questions and answers and training videos for participants inthe
      experimental group. Questionnaires were filled before and three months after the
      intervention in the two groups.Data were analyzed with SPSS-22 software for
      descriptive and analytical statistics. Results: The results of this studyshowed
      that the mean scores for knowledge, HBM constructs and self-examination behavior
      in the experimental groupwere elevated compared to the control group after the
      intervention (P<0.001). Conclusions: Education based on theHBM is effective in
      promoting breast self-examination behavior. Thus development and implementation
      of trainingprograms based on the model are proposed for officers involved in
      education and health promotion in Iran.

PMID- 29072431
TI  - Cal/OSHA Citations of Dental Practices.

PMID- 29072433
TI  - Life Outside the Operatory and Dental Ethics.

PMID- 29072432
TI  - Effectiveness of 7-Day and 14-Day Moxifloxacin-Dexlansoprazole Based Triple
      Therapy and Probiotic Supplement for Helicobacter Pylori Eradication in Thai
      Patients with Non-Ulcer Dyspepsia: A Double-Blind Randomized Placebo-Controlled
      Study
AB  - Background: Helicobacter pylori (H. pylori) is important cause of peptic ulcer
      and gastric cancer. Moxifloxacin iseffective antibiotic for treatment for H.
      pylori. However, there were limited studies as first line therapy. Probiotics had
      beenshown to decrease therapy-related side-effect and increase eradication rate.
      Aim of this study was to evaluate the efficacyof moxifloxacin-dexlansoprazole
      based triple therapy with probiotic for H. pylori treatment in Thailand.
      Methods:Patients with H. pylori infected gastritis were randomized to receive 7-
      or 14-day moxifloxacin-dexlansoprazole basedtriple therapy with probiotic or
      placebo. Regimen consisted of 60 mg dexlansoprazole twice daily, 400mg
      moxifloxacinonce daily, 1g clarithromycin MR once daily. Probiotic used in this
      study was 282.5mg Saccharomyces boulardii (S.boulardii) in capsule prescribed
      twice daily. CYP2C19 genotyping, antibiotic susceptibility tests, and CagA
      genotypingwere also done. Successful eradication was defined as a negative 13C
      urea breath test at least 4 weeks after treatment.Results: Total of 108 subjects
      was enrolled (27 each to 7-and 14-day regimens with probiotic or placebo).
      Antibioticsusceptibility tests showed 29% fluoroquinolone, 19% metronidazole and
      4% clarithromycin resistance. CYP2C19genotyping demonstrated 43%, 47% and 11%
      were rapid, intermediate and poor metabolizers, respectively. CagAgenes were
      positive in all patients. Eradication rates of 7-day and 14-day regimens with
      probiotic were 100%, and93% respectively. There were no significant differences
      between eradication rate of 7-day and 14-day regimen with orwithout probiotics.
      Regarding side-effects, incidence of nausea, abdominal discomfort, bitter taste,
      and diarrhea weresignificantly lower in regimen with probiotic group compared
      with placebo(7.4%vs. 22.2%; p=0.028, 0.00%vs.14.8%;p=0.003, 35.2%vs.70.4%;
      p=0.0002, and 0.00%vs.9.3%; p=0.028, respectively). Conclusions: 7-day
      moxifloxacindexlansoprazoletherapy plus S. boulardii provide an reliable cure
      rate of H. pylori in non-ulcer dyspeptic patientsin Thailand, independent of
      CYP2C19 genotype. Probiotic adding also decreased side effects during the
      treatment.

PMID- 29072434
TI  - Tech Trends: A look into the latest dental and general technology on the market.

PMID- 29072435
TI  - Inhibition of Topoisomerase IIalpha and Induction of Apoptosis in Gastric Cancer
      Cells by 19-Triisopropyl Andrographolide
AB  - Gastric cancer is the most common cancer in Eastern Asia. Increasing
      chemoresistance and general systemictoxicities have complicated the current
      chemotherapy leading to an urgent need of more effective agents. The presentstudy
      reported a potent DNA topoisomerase IIalpha inhibitory activity of an
      andrographolide analogue (19-triisopropylandrographolide, analogue-6) in gastric
      cancer cells; MKN-45, and AGS cells. The analogue was potently cytotoxic toboth
      gastric cancer cell lines with the half maximal inhibitory concentration (IC50
      values) of 6.3+/-0.7 MUM, and 1.7+/-0.05MUM at 48 h for MKN-45, and AGS cells,
      respectively. It was more potent than the parent andrographolide and
      theclinically used, etoposide with the IC50 values of >50 MUM in MKN-45 and
      11.3+/-2.9 MUM in AGS cells for andrographolideand 28.5+/-4.4 MUM in MKN-45 and
      4.08+/-0.5 MUM in AGS cells for etoposide. Analogue-6 at 2 MUM significantly
      inhibitedDNA topoisomerase IIalpha enzyme in AGS cells, induced DNA damage,
      activated cleaved PARP-1, and Caspase3 leadingto late cellular apoptosis.
      Interestingly, the expression of tumor suppressor p53 was not activated. These
      results showthe importance of 19-triisopropyl-andrographolide in its emerging
      selectivity to primary target on topoisomerase IIalphaenzyme, inducing DNA damage
      and apoptosis by p53- independent mechanism. Thereby, the results provide
      insights ofthe potential of 19-triisopropyl andrographolide as an anticancer
      agent for gastric cancer. The chemical transformationof andrographolide is a
      promising strategy in drug discovery of a novel class of anticancer drugs from
      bioactive naturalproducts.

PMID- 29072436
TI  - A Large Scale Study of the Epidemiology and Risk Factors for the Carcinogenic
      Liver Fluke Opisthorchis viverrini in Udon Thani Province, Thailand
AB  - Opisthorchis viverrini infection and cholangiocarcinoma are serious problems in
      South East Asia. This study aimed to find the prevalence of opisthorchiasis in
      various hosts in Udon Thani Province. Total fecal samples were collected from
      14,766 participants. The epidemiological data collected and analysed included
      prevalence and intensity of infection. Odds ratios (OR) were calculated to
      determine the associations between cross sectional data and to predict possible
      risk factors. The prevalence of O. viverrini infection in Udon Thani Province
      averaged 15.3% (eggs per gram (epg.) = 48.9 and range; 12-1, 320), with
      differences between villages (range; 3.8%-79.8%). An age-dependence for infection
      was observed to increase from ages 25 to 50 years and then decrease for older
      participants. A univariate analysis identified risk parameters including age (p =
      0.040; OR = 3.9 (95% CI = 1.2-7.5)), education (p < 0.0001; OR = 7.3 (95% CI =
      1.8-21.6)) and eating habits (p = 0.032; OR = 1.6 (95% C = 0.5-3.7)).
      Interestingly, most participants were not aware of treatments such as
      praziquantel (p < 0.0001; OR = 3.5 (95% CI = 1.4-11.6)), had no history of
      parasitic treatment (p = 0.486; OR = 1.5 (95% CI = 0.5-3.5) and had eaten raw
      fish (p=0.04; OR = 7.4 (95% CI = 1.5-18.6)). Liver fluke infection in dogs
      (18.1%, epg. = 44.7, range; 32-96) was significantly higher than in cats (11.0%,
      epg. = 117.8, range; 44-372) (p < 0.05). A positive association between O.
      viverrini infection in dogs and their owners was found. In addition, cyprinid
      fish dominantly infected by metacercaria including Henicorhynchus siamensis
      (27.7%), Cyclocheilichthys repasson (21.9%), Hampala dispar (14.1%), and
      Barbonymus gonionotus (6.9%). This study provides basic information required for
      the development of future effective and sustainable strategies to reduces
      infection rates, mainly by providing health education and encouraging behavioural
      changes.

PMID- 29072437
TI  - From Love and Fidelity to Infidelity- Individual Experiences of Women with Breast
      Cancer Regarding Relationships with Their Spouses
AB  - Background and Objective: Breast cancer and its treatment processes not only
      involve the patients but also theirspouses and can impact on mutual
      relationships. Spouses of women with breast cancer may experience
      devastatingconsequences of the disease in their marital and sexual relationships.
      Therefore, in the present study we aimed toinvestigate individual experiences of
      women with breast cancer in their relationships with their spouses. Materials
      andMethods: This was a qualitative study with a conventional approach to content
      analysis. A purposive sampling methodwas used to select 12 patients with breast
      cancer visiting the Chemotherapy Clinic in Zabol in 2016. Semi
      structuredinterviews were employed for data collection. Data trustworthiness was
      checked and data were analyzed based onthe steps proposed by Graneheim and
      Lundman. Ethical issues were considered. Results: Three main categories andten
      sub-categories were extracted. The three main categories were surrounded by
      misery, from emotional to practicalcompanionship and influencebeing imposed upon
      someone else. Conclusion: The findings showed paradoxicalexperiences of the women
      under study ranging from love and fidelity to infidelity. This indicates that
      some spousesdo not adequately support for their sick wives. Therefore, health
      professionals should provide support, guidance andtraining for couples, including
      sex therapy and counseling services, so that spouses can better support their
      wives.

PMID- 29072438
TI  - Economic Burden of Smoking in Iran: A Prevalence-Based Annual Cost Approach
AB  - Objectives: The burden of smoking on the health system and society is
      significant. The current study aimed toestimate the annual direct and indirect
      costs of smoking in Iran for the year 2014. Methods: A prevalence-based
      diseasespecificapproach was used to determine costs associated with the three
      most common smoking-related diseases: lungcancer (LC), chronic obstructive
      pulmonary disease (COPD) and ischaemic heart disease (IHD). Data on
      healthcareutilization were obtained from an original survey, hospital records and
      questionnaires. The number of deaths wasextracted from the global burden diseases
      study (GBD). The human capital approach was applied to estimate the costsof
      morbidity and mortality due to smoking-related diseases, classified as direct
      (hospitalization, outpatients and nonmedicalcosts) and indirect (mortality and
      morbidity). Results: The total economic cost of the three most commonsmoking
      attributable diseases in Iran was US$1.46 billion in 2014, including US$1.05
      billion (71.7%) in indirectand US$0.41 billion (28.3%) in direct costs. Direct
      costs of the three smoking-related diseases accounted for 1.6%of total healthcare
      expenditures and total costs were about 0.26% of Iran's gross domestic product
      (GDP) in 2014.Conclusions: Our study indicated that smoking places a substantial
      economic burden on Iranian society. Therefore,sustained smoking cessation
      interventions and tobacco control policies are required to reduce the magnitude
      and extentof smoking-attributable costs in Iran.

PMID- 29072439
TI  - Cu2ZnSnSe4 Thin Film Solar Cell with Depth Gradient Composition Prepared by
      Selenization of Sputtered Novel Precursors.
AB  - In this study, we proposed a new method for the synthesis of the target material
      used in a two stage process for preparation of a high quality CZTSe thin film.
      The target material consisting of a mixture of CuxSe and ZnxSn1-x alloy was
      synthesized, providing a quality CZTSe precursor layer for highly efficient CZTSe
      thin film solar cells. The CZTSe thin film can be obtained by annealing the
      precursor layers through a 30 min selenization process under a selenium
      atmosphere at 550  degrees C. The CZTSe thin films prepared by using the new
      precursor thin film were investigated and characterized using X-ray diffraction,
      Raman scattering, and photoluminescence spectroscopy. It was found that diffusion
      of Sn occurred and formed the CTSe phase and CuxSe phase in the resultant CZTSe
      thin film. By selective area electron diffraction transmission electron
      microscopy images, the crystallinity of the CZTSe thin film was verified to be
      single crystal. By secondary ion mass spectroscopy measurements, it was confirmed
      that a double-gradient band gap profile across the CZTSe absorber layer was
      successfully achieved. The CZTSe solar cell with the CZTSe absorber layer
      consisting of the precursor stack exhibited a high efficiency of 5.46%, high
      short circuit current (JSC) of 37.47 mA/cm2, open circuit voltage (VOC) of 0.31
      V, and fill factor (F.F.) of 47%, at a device area of 0.28 cm2. No crossover of
      the light and dark current-voltage (I-V) curves of the CZTSe solar cell was
      observed, and also, no red kink was observed under red light illumination,
      indicating a low defect concentration in the CZTSe absorber layer. Shunt leakage
      current with a characteristic metal/CZTSe/metal leakage current model was
      observed by temperature-dependent I-V curves, which led to the discovery of metal
      incursion through the CdS buffer layer on the CZTSe absorber layer. This leakage
      current, also known as space charge-limited current, grew larger as the
      measurement temperature increased and completely overwhelmed the diode current at
      a measurement temperature of 200  degrees C. This is due to interlayer diffusion
      of metal that increases the shunt leakage current and decreases the efficiency of
      the CZTSe thin film solar cells.

PMID- 29072440
TI  - Transient Carrier Cooling Enhanced by Grain Boundaries in Graphene Monolayer.
AB  - Using a high terahertz (THz) electric field (ETHz), the carrier scattering in
      graphene was studied with an electric field of up to 282 kV/cm. When the grain
      size of graphene monolayers varies from small (5 MUm) and medium (70 MUm) to
      large grains (500 MUm), the dominant carrier scattering source in large- and
      small-grained graphene differs at high THz field, i.e., there is optical phonon
      scattering for large grains and defect scattering for small grains. Although the
      electron-optical phonon coupling strength is the same for all grain sizes in our
      study, the enhanced optical phonon scattering in the high THz field from the
      large-grained graphene is caused by a higher optical phonon temperature,
      originating from the slow relaxation of accelerated electrons. Unlike the large
      grained graphene, lower electron and optical phonon temperatures are found in the
      small-grained graphene monolayer, resulting from the effective carrier cooling
      through the defects, called supercollisions. Our results indicate that the
      carrier mobility in the high-crystalline graphene is easily vulnerable to
      scattering by the optical phonons. Thus, controlling the population of defect
      sites, as a means for carrier cooling, can enhance the carrier mobility at high
      electric fields in graphene electronics by suppressing the heating of optical
      phonons.

PMID- 29072441
TI  - Multistimulative Nanogels with Enhanced Thermosensitivity for Intracellular
      Therapeutic Delivery.
AB  - The flexibility and hydrophilicity of nanogels suggest their potential for the
      creation of nanocarriers with good colloidal stability and stimulative ability.
      In the present study, biocompatible AGP and AGPA nanogels with triple-stimulative
      properties (thermosensitivity, pH sensitivity, and redox sensitivity) were
      prepared by incorporating poly(N-isopropylacrylamide) (PNIPAM) or poly(N
      isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) into alginate (AG) emulsion
      nanodrops, followed by fixation with a disulfide-containing molecule (cystamine
      dihydrochloride (Cys)). Compared to AG/PNIPAM(AGP) nanogels, AG/P(NIPAM-AA)
      (AGPA) nanogels exhibited more sensitive volumetric expansion by switching the
      temperature from 40 to 25  degrees C under physiological medium. This expansion
      occurs because P(NIPAM-AA) with -COOH groups can be fixed inside the nanogels via
      chemical bonding with Cys, whereas PNIPAM was encapsulated in the nanogels
      through simple physical interactions with the AG matrix. AGPA nanogels carrying
      an anticancer drug tend to easily enter cells upon heating, thereby exerting
      toxicity through a cold shock and reverse thermally induced release of an
      anticancer drug. Upon internalization inside cells, the nanogels use the
      reducible and acidic intracellular environments to effectively release the drug
      to the nucleus to impart anticancer activity. These results demonstrate that
      multifunctional nanogels may be used as a general platform for therapeutic
      delivery.

PMID- 29072442
TI  - Microwave Absorption and the Magnetic Hyperthermia Applications of
      Li0.3Zn0.3Co0.1Fe2.3O4 Nanoparticles in Multiwalled Carbon Nanotube Matrix.
AB  - Nanoparticles of Li0.3Zn0.3Co0.1Fe2.3O4 (LZC) were prepared by the sol-gel method
      and dried in a furnace at ~200  degrees C. The dried sample was annealed at 500,
      600, 700, and 800  degrees C for 5 h each. Rietveld analysis of X-ray diffraction
      patterns confirms the cubic Fd3m phase formation with lattice parameters ranged
      from 8.376 up to 8.390 A and allows the crystallite sizes (dcryst) to be
      estimated. To enhance microwave (MW) absorption as well as the effectiveness for
      hyperthermia treatment, nanoparticles are taken in the matrix of multiwalled
      carbon nanotubes (MWCNTs) and the morphology of the so-prepared samples
      (LZC@MWCNT) was studied by scanning electron microscopy and transmission electron
      microscopy analyses. Both static and dynamic magnetic properties were
      investigated on the samples of LZC nanoparticles and compared to those of the
      samples of LZC@MWCNT. The samples annealed at 500, 600, and 800  degrees C are
      excellent candidates in cancer treatment as ac magnetic heating analysis shows
      that the hyperthermia temperature (42  degrees C) was successfully achieved for
      an applied ac magnetic field of 420 Oe and 300 kHz frequency. MW absorption study
      also reveals that the samples of LZC@MWCNT could be used as a potential MW
      absorbing material for which a maximum reflection loss (RL) of ~-21 dB was
      achieved at a frequency of 15.27 GHz for only 1 mm layer thickness.

PMID- 29072443
TI  - BODIPYs for Dye-Sensitized Solar Cells.
AB  - BODIPY, abbreviation of boron-dipyrromethene, is one class of robust organic
      molecules that has been used widely in bioimaging, sensing, and logic gate
      design. Recently, BODIPY dyes have been explored for dye-sensitized solar cells
      (DSCs). Studies demonstrate their potential as light absorbers for the conversion
      of solar energy to electricity. However, their photovoltaic performance is
      inferior to many other dyes, including porphyrin dyes. In this review, several
      synthetic strategies of BODIPY dyes for DSCs and their further functionalization
      are described. The photophysical properties of dye molecules and their
      photovoltaic performances in DSCs are summarized. We aim to provide readers a
      clear picture of the field and expect to shed light on the next generation of
      BODIPY dyes for their applications in solar energy conversion.

PMID- 29072445
TI  - Integrated Graphene Oxide Purification-Lateral Flow Test Strips (iGOP-LFTS) for
      Direct Detection of PCR Products with Enhanced Sensitivity and Specificity.
AB  - An integrated graphene oxide purification-lateral flow test strip (iGOP-LFTS) was
      developed for on-strip purifying and visually detecting polymerase chain reaction
      (PCR) products with an improved sensitivity as well as a more stringent
      specificity. PCR products amplified with a pair of biotin- and digoxin-labeled
      primers were directly pipetted onto GO pads, on which graphene oxide selectively
      adsorbed residual primers and primer-dimers with the aid of a running buffer
      containing MgCl2 and Tween 20. By stacking up three GO pads to increase the
      surface area for adsorption, 83.4% of double-stranded DNA with a length of 30 bp
      and 98.6% of 20-nt primers could be removed from a 10-MUL DNA mixture. Since no
      primers interfered with detection, the increase of the sample loading volume from
      5 to 20 MUL could improve the signal-to-noise ratio of the test line 1.6 fold
      using the iGOP-LFTS while no changes were observed using the conventional LFTS.
      The limit of detection of the iGOP-LFTS was determined to be 30 copies of
      bacteriophage lambda-DNA with naked eyes and this limit could be further
      decreased to 3 copies by loading 20 MUL of the sample, which corresponded to a
      1000-fold improvement compared to that of the LFTS detected by naked eyes. When
      the ImageJ analysis was employed, a 100-fold decrease of the detection limit can
      be obtained. In addition, due to the removal of the primer-dimers, the dim test
      line observed in the negative control of the LFTS was eliminated using the iGOP
      LFTS. A mock clinical specimen spiked with defective HIV-1 (human
      immunodeficiency virus) viruses was successfully analyzed using a two-step
      reverse transcription-PCR with 30 amplification cycles followed by the iGOP-LFTS
      detection. These significant improvements were achieved without introducing any
      additional hands-on operations and instrumentations.

PMID- 29072446
TI  - Spin-Selective Photoreduction of a Stable Radical within a Covalent Donor
      Acceptor-Radical Triad.
AB  - Controlling spin-spin interactions in multispin molecular assemblies is important
      for developing new approaches to quantum information processing. In this work, a
      covalent electron donor-acceptor-radical triad is used to probe spin-selective
      reduction of the stable radical to its diamagnetic anion. The molecule consists
      of a perylene electron donor chromophore (D) bound to a pyromellitimide acceptor
      (A), which is, in turn, linked to a stable alpha,gamma-bisdiphenylene-beta
      phenylallyl radical (R*) to produce D-A-R*. Selective photoexcitation of D within
      D-A-R* results in ultrafast electron transfer to form the D+*-A-*-R* triradical,
      where D+*-A-* is a singlet spin-correlated radical pair (SCRP), in which both
      SCRP spins are uncorrelated relative to the R* spin. Subsequent ultrafast
      electron transfer within the triradical forms D+*-A-R-, but its yield is
      controlled by spin statistics of the uncorrelated A-*-R* radical pair, where the
      initial charge separation yields a 3:1 statistical mixture of D+*-3(A-*-R*) and
      D+*-1(A-*-R*), and subsequent reduction of R* only occurs in D+*-1(A-*-R*). These
      findings inform the design of multispin systems to transfer spin coherence
      between molecules targeting quantum information processing using the agency of
      SCRPs.

PMID- 29072444
TI  - A Free Energy Barrier Caused by the Refolding of an Oligomeric Intermediate
      Controls the Lag Time of Amyloid Formation by hIAPP.
AB  - Transiently populated oligomers formed en route to amyloid fibrils may constitute
      the most toxic aggregates associated with many amyloid-associated diseases. Most
      nucleation theories used to describe amyloid aggregation predict low oligomer
      concentrations and do not take into account free energy costs that may be
      associated with structural rearrangements between the oligomer and fiber states.
      We have used isotope labeling and two-dimensional infrared spectroscopy to
      spectrally resolve an oligomeric intermediate during the aggregation of the human
      islet amyloid protein (hIAPP or amylin), the protein associated with type II
      diabetes. A structural rearrangement includes the F23G24A25I26L27 region of
      hIAPP, which starts from a random coil structure, evolves into ordered beta-sheet
      oligomers containing at least 5 strands, and then partially disorders in the
      fibril structure. The supercritical concentration is measured to be between 150
      and 250 MUM, which is the thermodynamic parameter that sets the free energy of
      the oligomers. A 3-state kinetic model fits the experimental data, but only if it
      includes a concentration independent free energy barrier >3 kcal/mol that
      represents the free energy cost of refolding the oligomeric intermediate into the
      structure of the amyloid fibril; i.e., "oligomer activation" is required. The
      barrier creates a transition state in the free energy landscape that slows fibril
      formation and creates a stable population of oligomers during the lag phase, even
      at concentrations below the supercritical concentration. Largely missing in
      current kinetic models is a link between structure and kinetics. Our experiments
      and modeling provide evidence that protein structural rearrangements during
      aggregation impact the populations and kinetics of toxic oligomeric species.

PMID- 29072447
TI  - Facet-Selective Deposition of FeOx on alpha-MoO3 Nanobelts for Lithium Storage.
AB  - One-dimensional heterostructures have attracted significant interests in various
      applications. However, the selective deposition of shell material on specific
      sites of the backbone material remains a challenge. Herein, a facile facet
      selective deposition strategy has been developed for the construction of
      heterostructured alpha-MoO3@FeOx nanobelts. Because of the anisotropic feature of
      alpha-MoO3 nanobelts, the FeOx nanoparticles selectively deposit on the edges of
      alpha-MoO3 nanobelts, that is, the {100} and {001} facets. Such a heterostructure
      facilitates the electron transfer in lithium storage. As a result, the alpha
      MoO3@FeOx nanobelts exhibit high capacities of 913 mA h g-1 after 100 cycles at
      200 mA g-1 and 540 mA h g-1 after 100 cycles at 1000 mA g-1. The facet-selective
      deposition strategy developed here would be extended to the construction of other
      novel heterostructures with fascinating physical/chemical properties and wide
      potential applications.

PMID- 29072448
TI  - Carbon Quantum Dot-Induced MnO2 Nanowire Formation and Construction of a Binder
      Free Flexible Membrane with Excellent Superhydrophilicity and Enhanced
      Supercapacitor Performance.
AB  - Manganese oxides (MnO2) are regarded as typical and promising electrode materials
      for supercapacitors. However, the practical electrochemical performance of MnO2
      is far from its theoretical value. Nowadays, numerous efforts are being devoted
      to the design and preparation of nanostructured MnO2 with the aim of improving
      its electrochemical properties. In this work, ultralong MnO2 nanowires were
      fabricated in a process induced by carbon quantum dots (CQDs); subsequently, a
      binder-free flexible electrode membrane was easily obtained by vacuum filtration
      of the MnO2 nanowires. The effects of the CQDs not only induced the formation of
      one-dimensional nanostructured MnO2, but also significantly improved the
      wettability between electrode and electrolyte. In other words, the MnO2 membrane
      demonstrated a superhydrophilic character in aqueous solution, indicating the
      sufficient and abundant contact probability between electrode and electrolyte.
      The binder-free flexible MnO2 electrode exhibited a preeminent specific
      capacitance of 340 F g-1 at 1 A g-1; even when the current density reached 20 A g
      1, it still maintained 260 F g-1 (76% retention rate compared to that at 1 A g
      1). Moreover, it also showed good cycling stability with 80.1% capacity retention
      over 10 000 cycles at 1 A g-1. Furthermore, an asymmetric supercapacitor was
      constructed using the MnO2 membrane and active carbon as the positive and
      negative electrodes, respectively, which exhibited a high energy density of 33.6
      Wh kg-1 at 1.0 kW kg-1, and a high power density of 10 kW kg-1 at 12.5 Wh kg-1.

PMID- 29072449
TI  - Bromamine Decomposition Revisited: A Holistic Approach for Analyzing Acid and
      Base Catalysis Kinetics.
AB  - Chloramine chemistry is complex, with a variety of reactions occurring in series
      and parallel and many that are acid or base catalyzed, resulting in numerous rate
      constants. Bromide presence increases system complexity even further with
      possible bromamine and bromochloramine formation. Therefore, techniques for
      parameter estimation must address this complexity through thoughtful experimental
      design and robust data analysis approaches. The current research outlines a
      rational basis for constrained data fitting using Bronsted theory, application of
      the microscopic reversibility principle to reversible acid or base catalyzed
      reactions, and characterization of the relative significance of parallel
      reactions using fictive product tracking. This holistic approach was used on a
      comprehensive and well-documented data set for bromamine decomposition, allowing
      new interpretations of existing data by revealing that a previously published
      reaction scheme was not robust; it was not able to describe monobromamine or
      dibromamine decay outside of the conditions for which it was calibrated. The
      current research's simplified model (3 reactions, 17 constants) represented the
      experimental data better than the previously published model (4 reactions, 28
      constants). A final model evaluation was conducted based on representative
      drinking water conditions to determine a minimal model (3 reactions, 8 constants)
      applicable for drinking water conditions.

PMID- 29072450
TI  - Ebselen: Mechanisms of Glutamate Dehydrogenase and Glutaminase Enzyme Inhibition.
AB  - Ebselen modulates target proteins through redox reactions with
      selenocysteine/cysteine residues, or through binding to the zinc finger domains.
      However, a recent contradiction in ebselen inhibition of kidney type glutaminase
      (KGA) stimulated our interest in investigating its inhibition mechanism with
      glutamate dehydrogenase (GDH), KGA, thioredoxin reductase (TrxR), and glutathione
      S-transferase. Fluorescein- or biotin-labeled ebselen derivatives were
      synthesized for mechanistic analyses. Biomolecular interaction analyses showed
      that only GDH, KGA, and TrxR proteins can bind to the ebselen derivative, and the
      binding to GDH and KGA could be competed off by glutamine or glutamate. From the
      gel shift assays, the fluorescein-labeled ebselen derivative could co-migrate
      with hexameric GDH and monomeric/dimeric TrxR in a dose-dependent manner; it also
      co-migrated with KGA but disrupted the tetrameric form of the KGA enzyme at a
      high compound concentration. Further proteomic analysis demonstrated that the
      ebselen derivative could cross-link with proteins through a specific cysteine at
      the active site of GDH and TrxR proteins, but for KGA protein, the binding site
      is at the N-terminal appendix domain outside of the catalytic domain, which might
      explain why ebselen is not a potent KGA enzyme inhibitor in functional assays. In
      conclusion, ebselen could inhibit enzyme activity by binding to the catalytic
      domain or disruption of the protein complex. In addition, ebselen is a relatively
      potent selective GDH inhibitor that might provide potential therapeutic
      opportunities for hyperinsulinism-hyperammonemia syndrome patients who have the
      mutational loss of GTP inhibition.

PMID- 29072451
TI  - Chemical Imaging of Nanoscale Interfacial Inhomogeneity in LiFePO4 Composite
      Electrodes from a Cycled Large-Format Battery.
AB  - The nanoscale interfacial inhomogeneity in a cycled large-format LiFePO4 (LFP)
      composite electrode has been studied by X-ray photoemission electron microscopy
      at single particle spatial resolution with a probe depth of ~5 nm. The loss of
      active lithium in cycled LFP causes the coexsitence of fully delithiated LFP
      (FePO4) and partially delithiated LFP (Li0.6FePO4 or Li0.8FePO4) as a function of
      the extent of lithium loss. The distribution of various lithium loss phases along
      with local agglomeration of LFP and degradation of binder and carbon black are
      correlatively visualized. This is the first experimental exploration of chemical
      interplay between components in the composite electrode from a large-format
      battery, and implications on the LFP degradation in this battery are discussed.

PMID- 29072453
TI  - Microwave Synthesis of Thionated Naphthalene Diimide-Based Small Molecules and
      Polymers.
AB  - Thionated naphthalene diimides (NDIs) are promising materials for n-type organic
      semiconductors; despite their potential, synthetic routes to thionated NDIs are
      generally lengthy, nonselective, and low yielding and their polymeric analogues
      have yet to be reported in the literature. Here, we describe the rapid and
      selective thionation of thiophene- and selenophene-flanked NDIs using microwave
      irradiation and excess Lawesson's reagent. Remarkably, >99% conversion to the
      trans-dithionated product is observed by NMR within 45 min. Steric effects
      imparted by NDI core substituents prevent excess thionation, simplifying
      purification procedures. We apply this methodology to the postpolymerization
      thionation of NDI-based polymers to afford a series of polymers with varying
      degrees of thionation. Thionated NDIs exhibit bathochromic shifts of up to ~100
      nm in localized absorption maxima and increased electron affinities.

PMID- 29072454
TI  - High Molecular Weight Plant Polyphenolics (Tannins) as Biological Antioxidants.
AB  - Representative condensed and hydrolyzable tannins and related simple phenolics
      were evaluated as biological antioxidants using cyclic voltammetry, the
      metmyoglobin assay, and the deoxyribose assay. The redox potentials of the
      tannins were similar to those of structurally related simple phenolics. However,
      the tannins were 15-30 times more effective at quenching peroxyl radicals than
      simple phenolics or Trolox. One of the tannins, polygalloyl glucose, reacted an
      order of magnitude more quickly with hydroxyl radical than mannitol. These
      results suggest that tannins, which are found in many plant-based foods and
      beverages, are potentially very important biological antioxidants.

PMID- 29072452
TI  - Discovery of N-(6-Fluoro-1-oxo-1,2-dihydroisoquinolin-7-yl)-5-[(3R)-3
      hydroxypyrrolidin-1-yl]thiophene-2-sulfonamide (LSN 3213128), a Potent and
      Selective Nonclassical Antifolate Aminoimidazole-4-carboxamide Ribonucleotide
      Formyltransferase (AICARFT) Inhibitor Effective at Tumor Suppression in a Cancer
      Xenograft Model.
AB  - A hallmark of cancer is unbridled proliferation that can result in increased
      demand for de novo synthesis of purine and pyrimidine bases required for DNA and
      RNA biosynthesis. These synthetic pathways are frequently upregulated in cancer
      and involve various folate-dependent enzymes. Antifolates have a proven record as
      clinically used oncolytic agents. Our recent research efforts have produced LSN
      3213128 (compound 28a), a novel, selective, nonclassical, orally bioavailable
      antifolate with potent and specific inhibitory activity for aminoimidazole-4
      carboxamide ribonucleotide formyltransferase (AICARFT), an enzyme in the purine
      biosynthetic pathway. Inhibition of AICARFT with compound 28a results in dramatic
      elevation of 5-aminoimidazole 4-carboxamide ribonucleotide (ZMP) and growth
      inhibition in NCI-H460 and MDA-MB-231met2 cancer cell lines. Treatment with this
      inhibitor in a murine based xenograft model of triple negative breast cancer
      (TNBC) resulted in tumor growth inhibition.

PMID- 29072455
TI  - Self-Assembly of a Strong Polyhedral Oligomeric Silsesquioxane Core-Based
      Aspartate Derivative Dendrimer Supramolecular Gelator in Different Polarity
      Solvents.
AB  - Aromatic groups are introduced into the end peripherals of polyhedral oligomeric
      silsesquioxane (POSS) core-based organic/inorganic hybrid supramolecules to get a
      novel dendrimer gelator POSS-Z-Asp(OBzl) (POSS-ASP), which have eight aspartate
      derivative arms to make full use of strong pi-pi stacking forces to get strong
      supramolecular gels in addition to multiple hydrogen bindings and van der Waals
      interactions. POSS-ASP can self-assemble into three-dimensional nanoscale gel
      networks to provide hybrid physical gels especially with strong mechanical
      properties and fast-recovery behaviors. Two totally different morphologies of the
      connected spherical particle structures and banded ultralong fibers are observed
      owing to the polarity of solvents confirmed by the scanning electron microscopy,
      polarized optical microscopy, and transmission electron microscopy techniques,
      expecting the existing various self-assembly models and illustrating the
      peripherals of the dendrimer and the polarity of solvents having huge influences
      in the supramolecular self-assembly mechanism. What is more, the thermal
      stability, rheological properties, and network architecture information have also
      been investigated via tube-inversion, rotational rheometer, and powder X-ray
      diffraction methods, the results of which confirm the two different gel formation
      mechanisms that make POSS-ASP to exhibit two totally different thermal and
      mechanical properties. Such a study reports a new gelation system in organic or
      organic/aqueous mixed solvents, which can be helpful for investigating the
      relationship of dendritic supramolecular gelation and different polarity solvents
      during the supramolecular self-assembly process of gelators.

PMID- 29072456
TI  - Hierarchically Porous Carbon Derived from PolyHIPE for Supercapacitor and
      Deionization Applications.
AB  - Hierarchically porous carbon (HPC) materials with interconnected porous texture
      are produced from a porous poly(divinylbenzene) precursor, which is synthesized
      by polymerizing high-internal-phase emulsions. After carbonation, the macroporous
      structures of the poly(divinylbenzene) precursor are preserved and enormous micro
      /mesopores via carbonation with KOH are produced, resulting in an interconnected
      hierarchically porous network. The prepared HPC has a maximum specific surface
      area of 2189 m2 g-1. The electrode materials for supercapacitors and capacitive
      deionization devices employing the formed HPC exhibit a high specific capacity of
      88 mA h g-1 through a voltage range of 1 V (319 F g-1 at 1 A g-1) and a superior
      electrosorption capacity of 21.3 mg g-1 in 500 mg L-1 NaCl solution. The
      excellent capacitive performance could be ascribed to the combination of high
      specific surface area and favorable hierarchically porous structure.

PMID- 29072458
TI  - Coordination and Insertion: Competitive Channels for Borylene Reactions.
AB  - Monovalent boron, free borylene species of the form B-R are notoriously unstable.
      Consequently, there are substantial gaps in the literature concerning the
      potential utility of those species in organic and inorganic synthesis either as
      ligands or as critical intermediates in reactions. We show that the relative
      stability of borylene complexes varies widely, depending on the electron donating
      ability of the R group. We find that borylenes can form, in the gas phase, weak
      sigma hole type interactions to saturated carbon centers and stronger dative
      bonds to tetravalent silicon and germanium. An insertion reaction of the form
      FH3M + BR -> FH2MBHR competes against dative bonding, however, and the reaction
      is barrierless in several cases when M = Si and in a few cases when M = Ge. For M
      = C, the barriers are high enough to stabilize monovalent boron complexes. In
      each case, the barrier heights to M-H bond activation and BR insertion are very
      sensitive to the nucleophilicity of BR. We confirm, at the MP2(full) and CCSD(T)
      levels, a substantial preference in borylenes for the singlet over the triplet
      state. An account is provided at the B3LYP-D3 and MP2(full) levels for the facile
      insertion reaction on the singlet surface when M = Si and for the stability of
      FH3M.BR type complexes and the higher barriers to insertion when M = C and Ge.

PMID- 29072457
TI  - Cytotoxic Cardiac Glycoside Constituents of Vallaris glabra Leaves.
AB  - Thirteen cardenolide glycosides (1-13) were isolated from the CH2Cl2 and MeOH
      extracts of Vallaris glabra leaves. The structures of the new compounds (2-13)
      were identified by spectroscopic methods, with the absolute configurations of the
      sugar moieties determined by acid hydrolysis. All compounds were evaluated for
      their cytotoxic activity against human cervix adenocarcinoma, lung carcinoma, and
      colorectal adenocarcinoma cell lines. The two most potent compounds [2'-O
      acetylacoschimperoside P (1) and oleandrigenin-3-O-alpha-l-2'-O
      acetylvallaropyranoside (2)] exhibited IC50 values in the range of 0.03-0.07 MUM.

PMID- 29072459
TI  - Development and Application of a Coarse-Grained Model for PNIPAM by Iterative
      Boltzmann Inversion and Its Combination with Lattice Boltzmann Hydrodynamics.
AB  - The polymer poly(N-isopropylacrylamide) (PNIPAM) is studied using a novel
      combination of multiscale modeling methodologies. We develop an iterative
      Boltzmann inversion potential of concentrated PNIPAM solutions and combine it
      with lattice Boltzmann as a Navier-Stokes equation solver for the solvent. We
      study in detail the influence of the methodology on statics and dynamics of the
      system. The combination is successful and significantly simpler and faster than
      other mapping techniques for polymer solution while keeping the correct
      hydrodynamics. The model can semiquantitatively describe the correct phase
      behavior and polymer dynamics.

PMID- 29072460
TI  - Advantages of Relative versus Absolute Data for the Development of Quantitative
      Structure-Activity Relationship Classification Models.
AB  - The appropriate selection of a chemical space represented by the data set, the
      selection of its chemical data representation, the development of a correct
      modeling process using a robust and reproducible algorithm, and the performance
      of an exhaustive training and external validation determine the usability and
      reproducibility of a quantitative structure-activity relationship (QSAR)
      classification model. In this paper, we show that the use of relative versus
      absolute data in the representation of the data sets produces better
      classification models when the other processes are not modified. Relative data
      considers a reference frame to measure the chemical characteristics involved in
      the classification model, refining the data set representation and smoothing the
      lack of chemical information. Three data sets with different characteristics have
      been used in this study, and classifications models have been built applying the
      support vector machine algorithm. For randomly selected training and test sets,
      values of accuracy and area under the receiver operating characteristic curve
      close to 100% have been obtained for the generation of the models and external
      validations in all cases.

PMID- 29072461
TI  - Control of Fullerene Crystallization from 2D to 3D through Combined Solvent and
      Template Effects.
AB  - Achieving precise control of molecular self-assembly to form designed three
      dimensional (3D) structures is a major goal in nanoscale science and technology.
      Using scanning tunnelling microscopy and density functional theory calculations,
      we show that a 2D covalent organic framework (COF-1) can template solution
      processed C60 guest molecules to form several solvent-dependent structural
      arrangements and morphologies via a 2D to 3D growth process. When 1,2,4
      tricholorobenzene is used as solvent, C60 molecules form a template-defined close
      packed structure. When heptanoic acid is used as solvent, a range of lower
      density architectures that deviate from the template-defined close packing are
      observed. We attribute this difference to the co-adsorption of the heptanoic acid
      solvent molecules, which is only achieved in the presence of the template. This
      work demonstrates the possibility to precisely control 3D molecular self-assembly
      through the synergistic combination of template and solvent effects.

PMID- 29072462
TI  - Model for Microcapsule Drug Release with Ultrasound-Activated Enhancement.
AB  - Microbubbles and microcapsules of silane-polycaprolactone (SiPCL) have been
      filled with a fluorescent acridium salt (lucigenin) as a model for a drug-loaded
      delivery vehicle. The uptake and delivery were studied and compared with similar
      microbubbles and microcapsules of silica/mercaptosilica (S/M/S). Positively
      charged lucigenin was encapsulated through an electrostatic mechanism, following
      a Type I Langmuir isotherm as expected, but with an additional multilayer uptake
      that leads to a much higher loading for the SiPCL system (~280 MUg/2.4 * 109
      microcapsules compared with ~135 MUg/2.4 * 109 microcapsules for S/M/S). Whereas
      the lucigenin release from the S/M/S bubbles and capsules loaded below the
      solubility limit is consistent with diffusion from a monolithic structure, the
      SiPCL structures show distinct release patterns; the Weibull function predicts a
      general trend for diffusion from normal Euclidean space at short times tending
      toward diffusion out of fractal spaces with increasing time. As a slow release
      system, the dissolution time (Td) increases from 1 to 2 days for the S/M/S and
      for the low concentration, loaded SiPCl vehicles to ~10 days for the high loaded
      microcapsules. However, Td can be reduced on insonation to 2 days, indicating the
      potential to gain control over the local enhanced release with ultrasound. This
      was tested for a docetaxel model and its effect on C4-2B prostate cancer cells,
      showing improved cell toxicity for concentrations below the normal EC50 in
      solution.

PMID- 29072463
TI  - Specific Anion Effects on Na+ Adsorption at the Aqueous Solution-Air Interface:
      MD Simulations, SESSA Calculations, and Photoelectron Spectroscopy Experiments.
AB  - Specific ion effects of the large halide anions have been shown to moderate anion
      adsorption to the air-water interface (AWI), but little quantitative attention
      has been paid to the behavior of alkali cations. Here we investigate the
      concentration and local distribution of sodium (Na+) at the AWI in dilute (<1 M)
      aqueous solutions of NaCl, NaBr, and NaI using a combination of molecular
      dynamics (MD) and SESSA simulations, and liquid jet ambient pressure
      photoelectron spectroscopy measurements. We use SESSA to simulate Na 2p
      photoelectron intensities on the basis of the atom density profiles obtained from
      MD simulations, and we compare the simulation results with photoelectron
      spectroscopy experiments to evaluate the performance of a nonpolarizable force
      field model versus that of an induced dipole polarizable one. Our results show
      that the nonpolarizable force model developed by Horinek and co-workers (Chem.
      Phys. Lett. 2009, 479, 173-183) accurately predicts the local concentration and
      distribution of Na+ near the AWI for all three electrolytes, whereas the
      polarizable model does not. To our knowledge, this is the first interface
      specific spectroscopic validation of a MD force field. The molecular origins of
      the unique Na+ distributions for the three electrolytes are analyzed on the basis
      of electrostatic arguments, and shown to arise from an indirect anion effect
      wherein the identity of the anion affects the strength of the attractive Na+-H2O
      electrostatic interaction. Finally, we use the photoelectron spectroscopy results
      to constrain the range of inelastic mean free paths (IMFPs) for the three
      electrolyte solutions used in the SESSA simulations that are able to reproduce
      the experimental intensities. Our results suggest that earlier estimates of IMFPs
      for aqueous solutions are likely too high.

PMID- 29072464
TI  - Enantioselective Iridium-Catalyzed Hydrogenation of alpha-Keto Amides to alpha
      Hydroxy Amides.
AB  - A highly enantioselective iridium-catalyzed hydrogenation of alpha-keto amides to
      form alpha-hydroxy amides has been achieved with excellent results (up to >99%
      conversion and up to >99% ee, TON up to 100 000). As an example, this protocol
      was applied to the synthesis of (S)-4-(2-amino-1-hydroxyethyl)benzene-1,2-diol,
      the enantiomer of norepinephrine, which is widely used as an injectable drug for
      the treatment of critically low blood pressure. Density functional theory (DFT)
      calculations were also carried out to reveal the reaction mechanism.

PMID- 29072465
TI  - Two Prenyltransferases Govern a Consecutive Prenylation Cascade in the
      Biosynthesis of Echinulin and Neoechinulin.
AB  - Two prenyltransferases from Aspergillus ruber control the echinulin biosynthesis
      via exceptional sequential prenylations. EchPT1 catalyzes the first prenylation
      step, leading to preechinulin. The unique EchPT2 attaches, in a consecutive
      prenylation cascade, up to three dimethylallyl moieties to preechinulin and its
      dehydro forms neoechinulins A and B, resulting in the formation of at least 23 2-
      to 4-fold prenylated derivatives. Confirming these products in fungal extracts
      unravels the unprecedented catalytic relevance of EchPT2 for structural
      diversity.

PMID- 29072466
TI  - Direct C-H Cyanoalkylation of Heteroaromatic N-Oxides and Quinones via C-C Bond
      Cleavage of Cyclobutanone Oximes.
AB  - A direct C-H cyanoalkylation of heteroaromatic N-oxides and quinones with
      cyclobutanone oximes is reported. This redox-neutral, operationally simple
      cyanoalkylation reaction is successfully amenable to a wide range of
      heteroaromatic N-oxides, quinones, and cyclobutanone oximes. A novel catalytic
      system consisting of a nickel source proved crucial for cleavage of the C-C bond
      of cyclobutanone oximes and for selective C-C bond formation over beta-hydride
      elimination. Mechanistic studies suggest that a radical intermediate might be
      involved in this transformation.

PMID- 29072467
TI  - Synthetic Route to Oscillatoxin D and Its Analogues.
AB  - O-Methyloscillatoxin D and its analogues were concisely synthesized by a
      bioinspired intramolecular Mukaiyama aldol reaction as a key step, which involves
      the construction of a novel spiro-ether moiety.

PMID- 29072468
TI  - "Click Chemistry" Mediated Functional Microporous Organic Nanotube Networks for
      Heterogeneous Catalysis.
AB  - The synthesis of azide functional microporous organic nanotube networks (N3
      MONNs) via a Friedel-Crafts hyper-cross-linking reaction is reported.
      Subsequently, a general method for obtaining heterogeneous catalysts through a Cu
      catalyzed alkyne-azide reaction is presented. The small-molecule catalysts such
      as 2,2,6,6,-tetramethylpiperidine-1-oyl and 4-(N,N-dimethylamino)pyridine can be
      anchored into the MONNs. Owing to the hierarchically porous structure and high
      surface area, these catalysts show high activity in selective oxidation of
      alcohols and acylation reaction, respectively.

PMID- 29072469
TI  - Transition-Metal-Free Iodine Catalyzed Selenocayanation of Styrenyl Bromides and
      an Easy Access to Benzoselenophenes via Intermediacy of Styrenyl Selenocyanate.
AB  - A convenient procedure has been developed for the synthesis of styrenyl
      selenocyanates and benzoselenophenes from readily available styrenyl bromides by
      reaction with potassium selenocyanate in the presence of iodine under specified
      conditions. A series of both compounds have been obtained by this procedure. The
      synthesis of styrenyl selenocyanates has not been previously reported, and thus
      this method is of much significance.

PMID- 29072470
TI  - SN1-Type Alkylation of N-Heteroaromatics with Alcohols.
AB  - The organocatalytic alkylation of 2-methyl-N-heteroaromatics with alcohols has
      been achieved via SN1-type C(sp3)-H functionalization, providing a green and
      efficient synthesis of indole and ferrocene-functionalized N-heteroaromatics in
      high yields.

PMID- 29072471
TI  - The effects of paternal disengagement on women's perceptions of male mating
      intent.
AB  - Previous research demonstrates reliable associations between low paternal
      investment and daughters' precocious and risky sexual behavior. However, little
      is known about the psychological changes that occur in response to paternal
      disengagement that encourage these patterns. Here, we aim to redress this
      empirical gap by testing the effects of paternal disengagement on women's
      perceptions of male mating intent. In 4 experiments, women who described their
      fathers' absence (vs. a comparison state) perceived greater: mating intent in the
      described actions of a hypothetical dating partner (Study 1), sexual arousal in
      male target faces (Studies 2 and 3), and mating interest from a male confederate
      (Study 4). In a mixed-methods study (Study 5), women with greater developmental
      exposure to harsh-deviant paternal behavior perceived greater sexual intent in
      men's actions than women with lesser exposure. Moreover, these perceptual
      differences predicted unrestricted sociosexuality among women in this sample. An
      internal meta-analysis (N = 408) across studies provided support for a
      relationship between paternal disengagement and women's perceptions of male
      sexual intent. Together, this research suggests that low paternal investment
      (including primed paternal disengagement and harsh-deviant fathering) causes
      changes in daughters' perceptions of men that may influence their subsequent
      mating behavior. (PsycINFO Database Record

PMID- 29072472
TI  - Promoting emotion and behavior regulation in male prison inmates: A secondary
      data analysis from a randomized controlled trial testing the efficacy of the
      growing pro-social program.
AB  - This article describes a secondary data analysis collected from inmates who
      participated in an independent randomized controlled trial, testing the efficacy
      of the Growing Pro-Social (GPS) Program. The current study aimed to test the
      program's ability to increase, on one hand, cognitive reappraisal (adaptive
      emotion regulation strategy) and, on the other hand, decrease expressive
      suppression (maladaptive emotion regulation strategy) over time. It was also
      assessed if the GPS was capable of reducing disciplinary infractions committed by
      inmates over time. Participants were randomized to the GPS treatment (n = 121) or
      the control group (n = 133). The Emotion Regulation Questionnaire was completed
      at baseline, at mid-treatment, at post-treatment and at 12-months' follow-up.
      Disciplinary infractions were collected from prison records during the 12 months
      before the beginning of the program, during the GPS's 12-month length and during
      the 12 months after treatment completion. Treatment effects were analyzed with
      latent growth curve models. Concerning cognitive reappraisal, while treatment
      participants showed a significant increase, controls presented a decrease over
      time. For expressive suppression, the treatment group presented a significant
      decrease, and the control group showed no change over time. Treatment
      participants also presented a significant decrease in the number of disciplinary
      infractions and in the number of days in punishment, while controls showed no
      change or an increase over time. This study showed the GPS's ability to promote
      emotion and behavior regulation, which contributes not only to inmate's
      interpersonal adjustment, but also to a more efficient management of the prison
      system. (PsycINFO Database Record

PMID- 29072473
TI  - Associations between posttraumatic stress and legal charges among substance using
      veterans.
AB  - Substance misuse is prevalent among veterans entering the criminal justice
      system, and is related to recidivism. Research demonstrates that trauma exposure
      and posttraumatic stress (PTS) symptoms, which commonly co-occur with substance
      misuse, also increase the risk of legal involvement and recidivism. However, it
      is unclear whether the associations between trauma, PTS symptoms and violent and
      nonviolent crime may be conflated by substance use. The aim of the present study
      was to understand the association between PTS symptoms and criminal justice
      involvement (both violent and nonviolent crime) among substance-using veterans
      seeking Veterans Affairs (VA) specialty mental health care after accounting for
      substance use frequency and demographics including age, gender, and ethnicity.
      Further, this study examined whether specific clusters of PTS were associated
      with violent and nonviolent veteran offending. Participants included 697 veterans
      (52 women) aged 21 to 75 (M = 47.49, SD = 13.51) with a history of trauma
      exposure. Veterans self-reported past-month PTS symptoms, substance use, and
      lifetime legal charges. Logistic regression results indicated total PTS symptoms
      were associated with violent, but not nonviolent charges, above and beyond age,
      sex, race, cocaine use, and heavy alcohol use. Intrusion symptoms, in particular,
      were associated with violent charges. Results highlight the utility of examining
      PTS as a multifaceted construct and have implications for the assessment and
      treatment needs of justice-involved veterans. For example, the findings suggest
      that treatment needs appear to differ for those reporting violent or nonviolent
      offending, with a greater need for assessing and treating PTS for those involved
      with violent crime. (PsycINFO Database Record

PMID- 29072474
TI  - Resource scarcity, effort, and performance in physically demanding jobs: An
      evolutionary explanation.
AB  - Based on evolutionary theory, we predicted that cues of resource scarcity in the
      environment (e.g., news of droughts or food shortages) lead people to reduce
      their effort and performance in physically demanding work. We tested this
      prediction in a 2-wave field survey among employees and replicated it
      experimentally in the lab. In Study 1, employees who perceived resources in the
      environment to be scarce reported exerting less effort when their jobs involved
      much (but not little) physical work. In Study 2, participants who read that
      resources in the environment were scarce performed worse on a task demanding more
      (carrying books) but not less (transcribing book titles) physical work. This
      result was found even though better performance increased participants' chances
      of additional remuneration, and even though scarcity cues did not affect
      individuals' actual ability to meet their energy needs. We discuss implications
      for managing effort and performance, and the potential of evolutionary psychology
      to explain core organizational phenomena. (PsycINFO Database Record

PMID- 29072475
TI  - Emotion in the wilds of nature: The coherence and contagion of fear during
      threatening group-based outdoors experiences.
AB  - Emotional expressions communicate information about the individual's internal
      state and evoke responses in others that enable coordinated action. The current
      work investigated the informative and evocative properties of fear vocalizations
      in a sample of youth from underserved communities and military veterans while
      white-water rafting. Video-taped footage of participants rafting through white
      water rapids was coded for vocal and facial expressions of fear, amusement,
      pride, and awe, yielding more than 1,300 coded expressions, which were then
      related to measures of subjective emotion and cortisol response. Consistent with
      informative properties of emotional expressions, fear vocalizations were
      positively and significantly related to facial expressions of fear, subjective
      reports of fear, and individuals' cortisol levels measured after the rafting
      trip. It is important to note that this coherent pattern was unique to fear
      vocalizations; vocalizations of amusement, pride, and awe were not significantly
      related to fear expressions in the face, subjective reports of fear, or cortisol
      levels. Demonstrating the evocative properties of emotional expression, fear
      vocalizations of individuals appeared to evoke fear vocalizations in other people
      in their raft, and cortisol levels of individuals within rafts similarly
      converged at the end of the trip. We discuss how the study of spontaneous emotion
      expressions in naturalistic settings can help address basic yet controversial
      questions about emotions. (PsycINFO Database Record

PMID- 29072476
TI  - Oxytocin modulates charismatic influence in groups.
AB  - Charismatic leaders have had tremendous effects on the fortunes and fates of
      individuals and societies across the world. Via verbal and nonverbal signaling,
      such leaders form profound emotional bonds with followers. Despite evidence for
      its powerful effects, we know very little about what facilitates the charismatic
      relationship. Here, we argue that the neuropeptide oxytocin (OT), known to be
      implicated in parent-child attachment, also enhances the effects of charismatic
      leaders in groups. In a double-blind placebo-controlled study, we administered
      intranasal OT to participants, led by a confederate trained to exhibit charisma,
      and monitored participants' responses to the confederate's signaling while
      leading a group task. We found that OT enhanced the effects of 3 common
      manifestations of charismatic signaling-verbal behaviors, nonverbal behaviors,
      and followers' perceptions of the confederate's charisma-on classic outcomes of
      charismatic influence. Specifically, participants under OT showed more
      expressions of positive affect and mimicry of the leader in response to the
      confederate's signaling, and perceptions of the confederate's charisma had
      stronger effects on participants' willingness to trust each other. These findings
      extend the role of OT beyond the attachment bond to explain leader-follower
      relationships, shed light on the role of neuroendocrine factors in contagion
      processes in groups, and support the social saliency perspective of OT. We note,
      however, that because charisma was not manipulated, we had reduced control over
      the confederates' specific behaviors. We address this limitation in the
      Discussion, point to broader theoretical implications of our work, and offer
      ideas for future research. (PsycINFO Database Record

PMID- 29072478
TI  - The interactive effects of personality profiles and perceived peer drinking on
      early adolescent drinking.
AB  - Early adolescent drinking has been identified as an important risk factor for the
      development of alcohol dependence. Both perceived peer drinking and personality
      profiles have been implicated as risk factors for early adolescent drinking.
      However, research is yet to determine how these 2 factors may interact to
      increase such risk. This study aimed to determine whether personality profiles
      moderated the relationship between perceived peer drinking and early adolescent
      drinking. Baseline data were utilized in the analyses, from 3,287 adolescents
      (Mage = 13.51 years, SD = .58; 54% female; 78% born in Australia) participating
      in the Climate Schools Combined Study (a cluster randomized controlled trial with
      75 schools located across Queensland, New South Wales, and Western Australia,
      Australia). Lifetime consumption of alcohol, perceived peer drinking, and
      personality profiles (Substance Use Risk Profile Scale) were measured. A
      moderated binary logistic regression found the personality profiles of
      impulsivity, sensation seeking, and hopelessness were positively related to early
      adolescent drinking, whereas anxiety sensitivity had a negative association. A
      significant interaction revealed that adolescents with higher levels of sensation
      seeking and who perceived their peers to be drinking were significantly more
      likely to report early adolescent drinking (consumption of a full standard drink;
      OR = 1.043; 95% CI [1.018-1.069]). These results indicate that perception of peer
      drinking is more strongly associated with early adolescent drinking, when
      adolescents are also high on sensation seeking. Prevention and intervention
      programs could consider targeting both sensation seeking and perceived peer
      drinking in adolescents. (PsycINFO Database Record

PMID- 29072477
TI  - Mindfulness-based interventions for addictive behaviors: Implementation issues on
      the road ahead.
AB  - Over the past 35 years, mindfulness meditation practices have increasingly been
      integrated into Western medical settings. Research into the benefits of
      mindfulness-based interventions (MBIs) continues to expand, such that there are
      currently more than a dozen different protocolled MBIs for patients suffering
      from a variety of physical and psychological disorders. In the last decade, a
      number of MBIs specifically designed to treat addictive behaviors have been
      developed and tested. This review first provides a brief overview of the current
      state of the science with respect to the efficacy of MBIs for addictive
      behaviors, and some of the proposed mechanisms underlying the efficacy of MBIs.
      Second, the review highlights unresolved implementation issues and provides
      suggestions for how future research can address the implementation challenges to
      advance the delivery of MBIs. Specifically, this review focuses on the lack of
      clear empirical guidelines in the following areas: (a) effective training for MBI
      treatment providers; (b) adaptations of the traditional 2-hr closed-cohort group
      format; (c) delivery of MBIs in 1-on-1 treatment contexts; (d) delivery of MBIs
      at different points in the change process; (e) delivery of MBIs via technology
      based platforms; and (f) facilitation of precision medicine in the delivery of
      MBIs. Specific research directions are suggested with an eye toward a meaningful
      increase in access to MBIs for front-line clinicians and clients. (PsycINFO
      Database Record

PMID- 29072479
TI  - Postsecondary students with psychiatric disabilities identify core services and
      key ingredients to supporting education goals.
AB  - OBJECTIVE: Accessing and successfully completing postsecondary educational
      opportunities may be challenging for those living with psychiatric disabilities.
      This exploratory study highlights the experiences of individuals with psychiatric
      disabilities participating in postsecondary educational support initiatives.
      METHOD: Investigators conducted case studies with 3 education support initiatives
      across the United States. Focus groups revealed what concrete supported education
      services were helpful and key ingredients in delivering education supports.
      RESULTS: Access to specialists, mindfulness techniques, help with time management
      and procrastination, and facilitating classroom accommodations were identified as
      critical. Developing authentic relationships with supported education staff,
      flexibility in service delivery and access to student peers living with
      psychiatric disabilities were noted as key ingredients in service delivery.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Incorporating the voice of students
      with psychiatric disabilities into supported education services can increase
      access, involvement, and retention, therein providing more supports to students
      with psychiatric disabilities achieving their postsecondary education goals.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29072481
TI  - Classification accuracy of the Minnesota Multiphasic Personality Inventory-2
      (MMPI-2)-Restructured form validity scales in detecting malingered pain-related
      disability.
AB  - The symptom reports of individuals with chronic pain are multidimensional (e.g.,
      emotional, cognitive, and somatic) and significantly contribute to increased
      morbidity and lost work productivity. When pain occurs in the context of a
      legally compensable event, reliable assessment of a patient's multifactorial
      symptom experience during psychological or neuropsychological evaluations is a
      necessity. The Validity Scales of the Minnesota Multiphasic Personality Inventory
      2 (MMPI-2) have been shown useful in identifying symptom overreporting and
      feigning within chronic pain samples and a number of studies have emerged
      supporting the use of the MMPI-2-Restructured Form (MMPI-2-RF) in the detection
      of simulated or feigned impairment in a variety of populations. To date, only 1
      other study exists examining the ability of the MMPI-2-RF to detect exaggerated
      complaints using a strict operationalization of malingering exclusive to chronic
      pain samples. The purpose of this study was to examine the classification
      accuracy of MMPI-2-RF Validity Scales in a group of patients with chronic pain
      using a criterion-groups design. The final sample consisted of 501 clinical
      chronic pain patients assigned to groups based on the Bianchini, Greve, and Glynn
      (2005) criteria for Malingered Pain-Related Disability (MPRD). Results showed
      that all MMPI-2-RF Validity Scales differentiated malingerers from nonmalingerers
      with a high degree of accuracy. At cut-offs associated with >=95% Specificity,
      Sensitivities ranged from 15% (Fs) to 60% (Response Bias Scale; RBS). This study
      demonstrates that the MMPI-2-RF Validity Scales are capable of differentiating
      intentional symptom exaggeration from genuine complaints in a sample of
      incentivized chronic pain patients. (PsycINFO Database Record

PMID- 29072482
TI  - A new other-race effect for gaze perception.
AB  - The well-known other-race effect in face recognition has been widely studied,
      both for its theoretical insights into the nature of face expertise and because
      of its social and forensic importance. Here we demonstrate an other-race effect
      for the perception of a simple visual signal provided by the eyes, namely gaze
      direction. In Study 1, Caucasian and Asian participants living in Australia both
      showed greater perceptual sensitivity to detect direct gaze in own-race than
      other-race faces. In Study 2, Asian (Chinese) participants living in Australia
      and Asian (Chinese) participants living in Hong Kong both showed this other-race
      effect, but Caucasian participants did not. Despite this inconsistency, meta
      analysis revealed a significant other-race effect when results for all 5
      participant groups from corresponding conditions in the 2 studies were combined.
      These results demonstrate a new other-race effect for the perception of the
      simple, but socially potent, cue of direct gaze. When identical morphed-race eyes
      were inserted into the faces, removing race-specific eye cues, no other-race
      effect was found (with 1 exception). Thus, the balance of evidence implicated
      perceptual expertise, rather than social motivation, in the other-race effect for
      detecting direct gaze. (PsycINFO Database Record

PMID- 29072483
TI  - Time contracts and temporal precision declines when the mind wanders.
AB  - Our perception of time varies considerably from moment to moment, but how this
      variability relates to endogenous fluctuations in attentional states has been
      neglected. Here, we tested the hypothesis that perceptual decoupling during
      spontaneous mind wandering episodes distorts interval timing. In two studies with
      different visual subsecond interval timing paradigms, participants judged their
      attentional state on a trial-by-trial basis. Mind wandering states were
      characterized by underestimation of temporal intervals and a decline in temporal
      discrimination. Further analyses suggested that temporal contraction during mind
      wandering, but not the decline in temporal discrimination, could be attributed in
      part to attentional lapses. By contrast, we did not find any robust evidence that
      metacognition pertaining to interval timing was altered during mind wandering
      states. These results highlight the role of transient fluctuations in attentional
      states in intraindividual variability in time perception and have implications
      for the perceptual consequences, behavioral markers, and costs and benefits, of
      mind wandering. (PsycINFO Database Record

PMID- 29072484
TI  - Accelerometer-Assessed Physical Activity and Sedentary Time in Youth With
      Disabilities.
AB  - This study compared accelerometer-assessed habitual physical activity (PA),
      sedentary time, and meeting PA recommendations among 102 youth with disabilities
      (7-20 years) in four subgroups-physical/visual impairments, intellectual
      disability, autism spectrum disorders, and hearing impairment-and 800 youth with
      typical development (8-16 years). Low proportions of youth with disabilities met
      PA recommendations, and they generally were less physically active and more
      sedentary than youth with typical development. The hearing impairment and autism
      spectrum disorder groups were the most and least physically active, respectively.
      Older age and to some extent female sex were related to less PA and more
      sedentary time. Considering the suboptimal levels of PA in youth with
      disabilities, effective interventions directed at factors associated with PA
      among them are needed.

PMID- 29072480
TI  - The interpersonal theory of suicide: A systematic review and meta-analysis of a
      decade of cross-national research.
AB  - Over the past decade, the interpersonal theory of suicide has contributed to
      substantial advances in the scientific and clinical understanding of suicide and
      related conditions. The interpersonal theory of suicide posits that suicidal
      desire emerges when individuals experience intractable feelings of perceived
      burdensomeness and thwarted belongingness and near-lethal or lethal suicidal
      behavior occurs in the presence of suicidal desire and capability for suicide. A
      growing number of studies have tested these posited pathways in various samples;
      however, these findings have yet to be evaluated meta-analytically. This paper
      aimed to (a) conduct a systematic review of the unpublished and published, peer
      reviewed literature examining the relationship between interpersonal theory
      constructs and suicidal thoughts and behaviors, (b) conduct meta-analyses testing
      the interpersonal theory hypotheses, and (c) evaluate the influence of various
      moderators on these relationships. Four electronic bibliographic databases were
      searched through the end of March, 2016: PubMed, Medline, PsycINFO, and Web of
      Science. Hypothesis-driven meta-analyses using random effects models were
      conducted using 122 distinct unpublished and published samples. Findings
      supported the interpersonal theory: the interaction between thwarted
      belongingness and perceived burdensomeness was significantly associated with
      suicidal ideation; and the interaction between thwarted belongingness, perceived
      burdensomeness, and capability for suicide was significantly related to a greater
      number of prior suicide attempts. However, effect sizes for these interactions
      were modest. Alternative configurations of theory variables were similarly useful
      for predicting suicide risk as theory-consistent pathways. We conclude with
      limitations and recommendations for the interpersonal theory as a framework for
      understanding the suicidal spectrum. (PsycINFO Database Record

PMID- 29072485
TI  - Overcoming challenges associated with the bioanalysis of an ester prodrug and its
      active acid metabolite.
AB  - AIM: Bioanalysis of ester prodrugs represents a great analytical challenge due to
      poor matrix stability in the presence of esterases. Materials & methods: An
      approach that includes pH control, temperature and the use of an inhibitor
      (sodium fluoride, NaF) was employed for complete stabilization of an ester
      prodrug and its corresponding acid metabolite. Stability information was used to
      design a methodology with negligible ex vivo hydrolysis of the ester to the
      corresponding acid analyte during all critical parts of bioanalysis. Results &
      conclusion: The assay was fully validated to regulatory expectations and employed
      to support a preclinical Good Laboratory Practice study in rats. Incurred sample
      reanalysis was also conducted and the percent difference between repeat and
      original results were within +/-20%, thus confirming the repeatability of the
      assay.

PMID- 29072486
TI  - Multiplexing determination of cancer-associated biomarkers by surface-enhanced
      Raman scattering using ordered gold nanohoneycomb arrays.
AB  - AIM: Here, a multiplex surface-enhanced Raman scattering (SERS) based assay for
      simultaneous quantitation of carcinoembryonic antigen (CEA) and alpha-fetoprotein
      (AFP) was developed. METHODS: SERS tags of nanostars and SERS substrates of
      nanobowl arrays were functionalized with labeling and capturing antibodies,
      respectively. In presence of antigens, SERS tags, antigens and SERS substrates
      formed sandwich structure. RESULTS: The SERS-based technique showed a wide linear
      range from 0.5 to 100 ng/ml and detection limits were 0.41 and 0.35 ng/ml for CEA
      and AFP in phosphate-buffered saline buffer, respectively. Analysis results of
      clinical serum samples using this technique were similar to that shown in
      phosphate-buffered saline buffer. The LODs were 0.44 and 0.40 ng/ml for CEA and
      AFP, respectively. Conclusion: The precision and stability of this analysis
      technique were satisfactory, meanwhile, no obvious cross-reactivity could be
      found. What's more, it also suggested that this novel multiplex SERS-based
      technique could be a simple, specific, reliable, sensitive and multiplexed tool
      for important diagnostic and prognostic applications.

PMID- 29072487
TI  - Measuring Perceived Level of Integration During the Process of Primary Care
      Behavioral Health Implementation.
AB  - Provider- and staff-perceived levels of integration were measured during
      implementation of a primary care behavioral health clinic; these data were used
      to tailor and evaluate quality improvement strategies. Providers and staff at an
      urban, academic, adult primary care clinic completed the 32-item Level of
      Integration Measure (LIM) at baseline and 7 months. The LIM assesses 6 domains of
      integrated care. Overall and domain scores were calibrated from 0 to 100, with
      >=80 representing a highly integrated clinic. Response rate was 79% (N = 46/58)
      at baseline and 83% (N = 52/63) at follow-up. Overall, LIM score increased from
      64.5 to 70.1, P = .001. The lowest scoring domains at baseline were targeted for
      quality improvement and increased significantly: integrated clinical practice,
      60.0 versus 68.4, P < .001; systems integration, 57.0 versus 63.8, P = .001; and
      training, 56.7 versus 65.3, P = .001. Ongoing quality improvement, including
      organizational and financial strategies, is needed to achieve higher levels of
      integration.

PMID- 29072488
TI  - T3 subclassification using the EMD/mesorectum ratio predicts neoadjuvant
      chemoradiation outcome in T3 rectal cancer patients.
AB  - OBJECTIVE: To evaluate the feasibility of the EMD (extramural depth)/mesorectum
      ratio as a marker for T3 rectal cancer and its ability to predict tumour response
      to neoadjuvant chemoradiation and survival. METHODS: From 2010 to 2016, 284 T3
      rectal cancer patients who underwent high resolution MRI before neoadjuvant
      chemoradiation were enrolled. The EMD was defined as the distance from the outer
      edge of the muscularis propria to the outermost edge of the tumour. The
      measurement of the tumour EMD and mesorectum was in the same layer and their
      ratio was calculated. Receiver operating characteristic analysis and relative
      area under the curve statistics were used to choose the cut-off value. The
      association of the EMD/mesorectum ratio and other MRI or clinical factors with
      the tumour regression grade (TRG) was analysed. Cox regression analysis was used
      to estimate independent risk factors for disease-free survival (DFS) and overall
      survival (OS). RESULTS: The mean EMD/mesorectum ratio was 0.47 +/- 0.3. We chose
      an EMD/mesorectum ratio of 0.5 in further analyses after receiver operating
      characteristic analysis. Of 284 patients, 177 (62.3%) had an EMD/mesorectum ratio
      <= 0.5. Patients with an EMD/mesorectum ratio <= 0.5 had a higher TRG 0-1 rate
      than patients with a ratio >0.5 (53.1% vs 36.4%, p = 0.006). A multivariate
      analysis identified that an EMD/mesorectum ratio >0.5 [hazard ratio (HR) 2.020; p
      = 0.028] and ypTNM II-III (HR 3.550; p = 0.017) were independent prognostic
      factors to indicate decreased DFS. For OS, only patients with TRG 2-3 had
      decreased OS compared with patients with TRG 0-1 (HR 2.959; p = 0.035).
      CONCLUSION: When the EMD/mesorectum ratio was applied to categorize T3 rectal
      cancer patients, the ratio of 0.5 can be used as a cut-off value for T3 rectal
      cancer. Patients with a ratio <= 0.5 had a higher response rate and better DFS.
      However, further validation is needed in a larger sample of patients. Advances in
      knowledge: The EMD/mesorectum ratio may serve to predict tumour response to
      neoadjuvant chemoradiation and survival in T3 rectal cancer patients.

PMID- 29072490
TI  - Immunoprecipitation middle-up LC-MS for in vivo drug-to-antibody ratio
      determination for antibody-drug conjugates.
AB  - AIM: Drug-to-antibody ratio (DAR) determination is critical for development of
      antibody-drug conjugates (ADCs). This work presents a middle-up LC-MS approach
      for DAR analysis using prelabeled capture beads and in-house fabricated slit
      plates. Methodology & Results: Cysteine, engineered cysteine and disulfide-linked
      ADCs, each with two different linker payloads, were immunocaptured and digested
      to scFc and F(ab')2 fragments. At this point, disulfide-linked ADCs were analyzed
      while cysteine and engineered cysteine ADCs were reduced to LC and Fd' fragments
      for analysis. Results were precise, accurate and sensitive, allowing DAR to be
      determined out to 21 days. CONCLUSION: This work describes a method that is
      easily implemented, amenable to high-throughput analysis and does not require
      specialized reagents or equipment.

PMID- 29072491
TI  - Influence of Wrist Position on the Metacarpophalangeal Joint Motion of the Index
      Through Small Finger.
AB  - BACKGROUND: The metacarpophalangeal joints exhibit range of motion that is
      influenced by wrist position. Synergistic motion occurs between the wrist and the
      metacarpophalangeal joints with different static wrist positions affecting
      joints' motion capability. The aim of this study was to determine how different
      wrist positions influence the active range of motion of the index through small
      finger metacarpophalangeal joints. METHODS: The active range of motion of the
      index through small finger metacarpophalangeal joints of 31 healthy subjects was
      measured in flexion/extension and radial/ulnar deviation in 5 different
      flexion/extension wrist positions, using biaxial electrogoniometers. RESULTS:
      There was a difference in range of motion of all fingers depending on the wrist
      position. The minimum metacarpophalangeal joint range of motion was found in 80
      degrees  wrist extension, the maximum in neutral wrist position. For the index
      finger, flexion/extension was 84.7 degrees  (+/-8.6 degrees ) to 25.9 degrees 
      (+/-10.2 degrees ) and radial/ulnar deviation was 32.1 degrees  (+/-11.3 degrees
      ) to 22.6 degrees  (+/-12.8 degrees ). For the middle finger, flexion/extension
      was 84.8 degrees  (+/-8.5 degrees ) to 25.9 degrees  (+/-10.1 degrees ) and
      radial/ulnar deviation 28.8 degrees  (+/-11.1 degrees ) to 22.1 degrees  (+/
      8.9). The fourth finger showed a range of motion for flexion/extension of 87.2
      degrees  (+/-11.5 degrees ) to 22.8 degrees  (+/-11.6 degrees ) and radial/ulnar
      deviation of 8.1 degrees  (+/-5.8 degrees ) to 32.3 degrees  (+/-12.4 degrees ).
      The highest range of motion was measured at the fifth finger with
      flexion/extension of 84.0 degrees  (+/-8.6 degrees ) to 32.1 degrees (+/-16.8
      degrees ) and radial/ulnar deviation of 15.1 degrees  (+/-12.9 degrees ) up to
      54.6 degrees  (+/-18.7 degrees ). CONCLUSIONS: The range of motion of the index
      through small finger metacarpophalangeal joints was significantly influenced by
      wrist position. The highest metacarpophalangeal joint range of motion of all
      fingers was conducted in neutral wrist positions. Apart from ergonomic
      implications, we conclude that metacarpophalangeal joint motion should be
      assessed under standardized wrist positions.

PMID- 29072489
TI  - Effects of losartan on vasomotor function and canonical transient receptor
      potential channels in the aortas of sinoaortic denervation rats.
AB  - Increased short-term blood pressure variability (BPV) is strongly correlated with
      target organ damage. However, the molecular mechanisms underlying abnormal BPV
      induced organ damage and effective therapeutic targets are poorly understood. The
      purpose of this study was to investigate the effects of losartan on vasomotor
      function and canonical transient receptor potential (TRPC) channels in the aortas
      of rats with arterial pressure lability induced by sinoaortic denervation (SAD).
      SAD was performed in male Sprague-Dawley rats at the age of 10 weeks. The
      experiment included sham-operated (Sham), SAD, and losartan-treated SAD (SAD+Los)
      groups. After 8 weeks of treatment, hemodynamic parameters were measured via
      catheterization, thoracic aortic vasomotor functions were evaluated using a
      physiological vascular ring tension recording system, and TRPC1 and 6 mRNA and
      protein expression levels in the endothelial cells (ECs) and smooth muscle cells
      (SMCs) of the thoracic aorta were determined via reverse transcription polymerase
      chain reaction (RT-PCR) and Western-blotting, respectively. Compared with Sham
      rats, SAD rats exhibited significantly increased BPV, enhanced norepinephrine
      induced aortic contraction, and attenuated acetylcholine-induced aortic
      relaxation. Both the mRNA and the protein expression levels of TRPC1 and 6 were
      significantly downregulated in the ECs and upregulated in the SMCs of the
      thoracic aortas of SAD rats. Losartan treatment prevented these SAD-induced
      changes. In conclusion, losartan efficiently prevented vasomotor function
      impairment in SAD rats by reducing BPV and regulating TRPC1 and 6 expression
      levels.

PMID- 29072492
TI  - Strategies for reducing ovarian dose in volumetric modulated arc therapy (VMAT)
      for postoperative uterine cervical cancer.
AB  - OBJECTIVE: To reduce the ovarian dose with volumetric modulated arc therapy
      (VMAT), an original VMAT was designed with two types of arcs to restrict angles
      and fields (R-VMAT). METHODS: The subjects were 11 patients who underwent ovarian
      transposition with clips left by a surgeon. Three methods, intensity-modulated
      radiotherapy (IMRT), standard VMAT (S-VMAT) and R-VMAT, were optimized for
      assessment of the ovarian dose with the target coverage kept high. RESULTS: The
      homogeneity and conformity indexes for the planning target volume (PTV) were
      similar for the three methods. However, the average +/- SD of the ovarian mean
      dose (OMD) was 5.0 +/- 1.5, 4.9 +/- 1.9 and 3.5 +/- 1.4 Gy, and the percentage of
      ovarian volume exceeding 5 Gy (V5) was 41.5 +/- 34.1%, 34.1 +/- 38.05% and 8.4 +/
      20.5% for IMRT, S-VMAT and R-VMAT, respectively. The OMD and V5 were
      significantly smaller for R-VMAT than for the other plans (p < 0.01). Correlation
      values between the OMD and the lateral distance from the ovaries to the PTV
      surface were 0.86, 0.81 and 0.82 for IMRT, S-VMAT and R-VMAT, respectively.
      CONCLUSION: These findings suggest that R-VMAT delivered the lowest dose to the
      ovaries. To reduce the OMD to less than 3 Gy, ovaries should be transposed
      laterally 6.1 cm away from the PTV surface when R-VMAT is used. Advances in
      knowledge: When organs with high susceptibility to radiation, such as ovaries,
      are near the PTV, R-VMAT is superior to IMRT and S-VMAT.

PMID- 29072493
TI  - Generation of assay positive controls for detection of isotype anti-drug
      antibodies for immunogenicity monitoring.
AB  - AIM: Development of drug-related surrogate positive controls for isotype anti
      drug antibodies assay remains challenging. Efforts on antibody engineering or
      chemical crosslinking have been made. However, multiple epitope recognition,
      purity and stability are often of concern. To tackle these challenges, we used LC
      SPDP/SMPB crosslinking to conjugate polyclonal anti-drug IgG and human
      immunoglobulin isotype (hIgE, hIgA, hIgM or hIgG4) with optimized conditions.
      RESULTS: The final product was a hybrid of anti-drug IgG cross-linked to human
      isotype immunoglobulin through stable thioether bond. The characteristics of the
      hybrids and their performance as assay positive controls were further evaluated.
      CONCLUSION: The results demonstrate that LC-SPDP/SMPB chemical crosslinking
      method is suitable for generating stable hybrids to be used as assay positive
      controls in isotype anti-drug antibodies assay.

PMID- 29072494
TI  - "I Will Communicate With You, But Let Me Be In Control": Understanding How
      Parents Manage Private Information About Their Chronically Ill Children.
AB  - Parents have a significant role in the management of a child's chronic condition.
      Parents are often the only consistent individuals managing a child's health
      across his or her childhood and adolescence (e.g., present for all appointments
      and medical procedures). Many of the responsibilities required of parents involve
      communication work, where parents must strategically and actively design messages
      as they interact with medical professionals, other family, and friends. Using
      communication privacy management theory, we analyzed interviews conducted with 35
      parents to understand the motivations and strategies involved in their regulation
      of information about their child's chronic condition. These findings have
      important practical implications because parental involvement in a chronically
      ill child's care has direct effects on familial adaptation and adjustment.

PMID- 29072495
TI  - Distraction Osteogenesis and Fusion for Failed First Metatarsophalangeal Joint
      Replacement: Case Series.

PMID- 29072496
TI  - Immunoaffinity LC-MS/MS for quantitative determination of a free and total
      protein target as a target engagement biomarker.
AB  - AIM: IP-10 is a protein target for the treatment of Crohn's disease. Inhibition
      of IP-10 by anti-IP-10 mAbs neutralizes its various biological activities. The
      measurement of free IP-10 suppression as a target engagement biomarker is
      required for the assessment of drug effect on the target. RESULTS: The
      development of highly sensitive immunoaffinity-LC-MS/MS assays for quantifying
      free and total IP-10 in cynomolgus monkey serum is reported for the first time.
      This paper details strategies for maximizing assay sensitivity by selecting
      digestion routes, and optimizing immunocapture to achieve full recovery and
      minimal matrix effect. For the free IP-10 assay, bioanalytical strategies have
      been established to minimize drug/ligand dissociation. CONCLUSION: The assays
      have been implemented for target engagement measurement, pharmacokinetic
      pharmacodynamic correlation, and human dose projections.

PMID- 29072497
TI  - Efficacy and safety of ultrasound guided percutaneous glue embolization in
      iatrogenic haemorrhagic complications of paracentesis and thoracocentesis in
      cirrhotic patients.
AB  - OBJECTIVE: To compare the safety and efficacy of ultrasound guided percutaneous
      glue (N-butyl-2-cyanoacrylate) embolization with transarterial embolization in
      the management of iatrogenically injured arteries while performing paracentesis
      or thoracocentesis in patients with chronic liver disease. METHODS: Hospital
      database was searched for cirrhotic patients having abdominal/thoracic wall
      haemorrhage following paracentesis/thoracocentesis procedure from January 2011 to
      June 2016. Doppler ultrasound and/or CT angiography were used to localize the
      site of haemorrhage and patients were treated by transarterial embolization or
      ultrasound-guided percutaneous glue embolization. Technical success was defined
      as cessation of haemorrhage as evidenced by angiography/Doppler ultrasound and
      clinical success was evaluated in terms of stabilization of the vital signs
      without the need for further transfusion or pressors, and survival. In both
      groups, the time to "imaging diagnosis of haemorrhage" and "successful
      embolization" with the outcome was analysed. RESULTS: 23 cirrhotic patients had
      bleeding following a percutaneous procedure, 8 (Group 1) of them underwent
      transarterial embolization while 15 (Group 2) underwent ultrasound-guided
      percutaneous glue embolization. Mean time needed for embolization in Group 1 was
      41 min while in Group 2 was 9 min (p < 0.001). Technical success was achieved in
      all but one case requiring repeat glue embolization. Initial clinical improvement
      was noted in all cases but the 30-day mortality owing to all causes was not
      significantly different between treatment groups. CONCLUSION: The study and its
      outcome suggest that ultrasound guided percutaneous glue embolization is a quick
      and effective treatment for iatrogenic haemorrhage following
      paracentesis/thoracocentesis in cirrhotic patients with comparable results to
      transarterial embolotherapy. Advances in knowledge: This study details an
      innovative technique of ultrasound guided percutaneous glue embolization of the
      iatrogenically injured vessel in the management of active extravasation and
      pseudoaneurysm developing after paracentesis/thoracocentesis in patients with
      cirrhosis.

PMID- 29072499
TI  - Factors that impact pharmacokinetic measurements of antibody therapeutics: what
      is your PK assay telling you?

PMID- 29072498
TI  - Exploring the Influence of Differentiated Nutrition Information on Consumers'
      Mental Models Regarding Foods from Edible Insects: A Means-End Chain Analysis.
AB  - This study used a field experiment and means-end chain analysis to examine the
      effects of positive and perceived negative nutrition information on the
      households' motivations to consume insect-based foods. It used a random sample of
      households drawn from rural communities in Kenya. The study found that provision
      of nutrition information on benefits of edible insects and perceived negative
      aspects of insect-based foods influences participants' perceptions of insect
      based foods and hence acceptance. We also found that tasting real products
      influenced the nature of mental constructs. The results provide marketers of
      edible insects with potential marketing messages for promotion.

PMID- 29072500
TI  - Poor Sleep Has Negative Implications for Children With and Without ADHD, but in
      Different Ways.
AB  - BACKGROUND: Sleep problems are commonly reported in attention deficit
      hyperactivity disorder (ADHD), and are also a familiar characteristic of typical
      development (TD). We sought to elucidate the relationship between sleep, ADHD
      trait behaviors, and cognitive inattention, and how it manifests between ADHD and
      TD children. PARTICIPANTS: Eighteen children diagnosed with ADHD and 20 age
      matched TD controls aged 5 to 11 years old participated in the study. METHODS:
      Sleep profiles were assessed using Children's Sleep Habits Questionnaire and
      actigraphy measures. Behavioral functioning was examined using Conners' Parent
      Report Scale and attention using the computerized Conners' Continuous Performance
      Task. RESULTS: We found evidence of (a) poorer sleep quality in the ADHD group,
      despite no difference in actual sleep time, (b) poor sleep quality in TD children
      predicting increased ADHD-trait behaviors, despite no association with attention,
      and (c) a consistent trend for poor sleep quality predicting reduced attentional
      control in ADHD children, despite no association with behavior. CONCLUSIONS: Poor
      sleep quality affects developmental subgroups in different ways. For ADHD
      children, poor sleep worsens their predisposed attentional deficit, while for TD
      children it mimics ADHD behaviors. These findings have important implications for
      the debate on overdiagnosis of childhood ADHD, and the use of sleep-based
      interventions. Above all, they highlight the importance of promoting good sleep
      hygiene in all children.

PMID- 29072502
TI  - Improving hemodynamics of cardiovascular system under a novel intraventricular
      assist device support via modeling and simulations.
AB  - Ventricular assist devices (LVADs) are increasingly recognized for supporting
      blood circulation in heart failure patients who are non-transplant eligible.
      Because of its volume, the traditional pulsatile device is not easy to implant
      intracorporeally. Continuous flow LVADs (CF-LVADs) reduce arterial pulsatility
      and only offer continuous flow, which is different from physiological flow, and
      may cause long-term complications in the cardiovascular system. The aim of this
      study was to design a new pulsatile assist device that overcomes this
      disadvantage, and to test this device in the cardiovascular system. Firstly, the
      input and output characteristics of the new device were tested in a simple
      cardiovascular mock system. A detailed mathematical model was established by
      fitting the experimental data. Secondly, the model was tested in four
      pathological cases, and was simulated and coupled with a fifth-order
      cardiovascular system and a new device model using Matlab software. Using
      assistance of the new device, we demonstrated that the left ventricle pressure,
      aortic pressure, and aortic flow of heart failure patients improved to the levels
      of a healthy individual. Especially, in state IV level heart failure patients,
      the systolic blood pressure increased from 81.34 mmHg to 132.1 mmHg, whereas the
      diastolic blood pressure increased from 54.28 mmHg to 78.7 mmHg. Cardiac output
      increased from 3.21 L/min to 5.16 L/min. The newly-developed assist device not
      only provided a physiological flow that was similar to healthy individuals, but
      also effectively improved the ability of the pathological ventricular volume.
      Finally, the effects of the new device on other hemodynamic parameters are
      discussed.

PMID- 29072501
TI  - Early short-term treatment with exogenous hydrogen sulfide postpones the
      transition from prehypertension to hypertension in spontaneously hypertensive
      rat.
AB  - ABSTACT Hydrogen sulfide (H2S), nitric oxide (NO), and renin-angiotensin system
      (RAS) are involved in hypertension. We examined whether early treatment with
      sodium hydrosulfide (NaHS), an exogenous H2S donor, can regulate H2S-generating
      pathway, NO pathway, and the RAS, to prevent the transition from prehypertension
      to hypertension in spontaneously hypertensive rats (SHRs). Four-week-old SHRs and
      control normotensive Wistar-Kyoto (WKY) rats were assigned into three groups:
      WKY, SHRs, and SHR + NaHS; SHRs were injected intraperitoneally with sodium
      hydrosulfide (14 MUmol/kg/day) for 4 weeks. SHRs exhibited hypertension at 12
      weeks of age, which was blocked by early sodium hydrosulfide administration.
      Concentrations of H2S were increased in the kidney in SHR + NaHS group versus
      WKY. Sodium hydrosulfide reduces mRNA expression of four H2S-generating enzymes
      and decreased 3-mercaptopyruvate sulphurtransferase protein level in SHRs. Early
      administration of sodium hydrosulfide decreases plasma NG monomethyl-l-arginine
      (l-NMMA, an inhibitor of NO synthase) level and increases plasma NO level in
      SHRs. Next, sodium hydrosulfide administration reduces renal mRNA expression of
      Ren, Atp6ap2, Agt, Ace, and Agtr1a in SHRs. We conclude that early short-term
      sodium hydrosulfide treatment increases renal H2S concentrations, restores NO
      bioavailability, and blocks the RAS in the kidney, in favor of vasodilatation to
      prevent the development of hypertension in adult SHRs.

PMID- 29072503
TI  - A segmentation of brain MRI images utilizing intensity and contextual information
      by Markov random field.
AB  - BACKGROUND AND OBJECTIVE: Image segmentation is a preliminary and fundamental
      step in computer aided magnetic resonance imaging (MRI) images analysis. But the
      performance of most current image segmentation methods is easily depreciated by
      noise in MRI images. A precise and anti-noise segmentation of MRI images is
      desired in modern medical image diagnosis. METHODS: This paper presents a
      segmentation of MRI images which combines fuzzy clustering and Markov random
      field (MRF). In order to utilize gray level information sufficiently and
      alleviate noise disturbance, fuzzy clustering is carried out on the original
      image and the coarse scale image of multi-scale decomposition. The spatial
      constraints between neighboring pixels are modeled by a defined potential
      function in the MRF to reduce the effect of noise and increase the integrity of
      segmented regions. Spatial constraints and the gray level information refined by
      Fuzzy C-Means (FCM) algorithm are integrated by maximum a posteriori Markov
      random field (MAP-MRF). In the proposed method, the fuzzy clustering membership
      obtained from the original image and the coarse scale image is integrated into
      the single-site clique potential functions by MAP-MRF. The defined potential
      functions and the distance weight are introduced to model the neighborhood
      constraint with MRF. RESULTS: The experiments are carried out on noised synthetic
      images, simulated brain MR images and real MR images. The experimental results
      show that the proposed method has strong robustness and satisfying performance.
      Meanwhile the method is compared with FCM, FGFCM and FLICM algorithms visually
      and statistically in the experiments. In the comparison, the proposed method has
      achieved the best results. In the statistical comparison, the proposed method has
      an average similarity index of 36.8%, 33.7%, 2.75% increase against FCM, FGFCM
      and FLICM. CONCLUSIONS: This paper proposes a MRI segmentation method combining
      fuzzy clustering and Markov random field. The method is tested in the noised
      image databases and comparison experiments, which shows that it is a precise and
      robust MRI segmentation method.

PMID- 29072504
TI  - Design of a new haptic device and experiments in minimally invasive surgical
      robot.
AB  - In this paper, we designed a 8 degrees of freedom (DOFs) haptic device for
      applications in minimally invasive surgical robot. The device can provide three
      translational, three rotational and a grasping motion and force feedback
      capability. It is composed of three parts, including an arm mechanism, a
      redundant wrist mechanism and a grasper mechanism. The kinematics and gravity
      compensation algorithms are also detailed in the paper. In addition, the haptic
      device and a slave surgical robot for minimally invasive surgery (MIS) developed
      by our lab are integrated as a master-slave surgical robotic system in this
      paper. In the master-slave robotic system, a new control system is designed to
      realize real-time mater-slave control based on EtherCAT bus technology.
      Experiments show that the haptic device can effectively compensate gravity at any
      position in its workspace and successfully realize master-slave operation by the
      control method, which prove the haptic device designed in this paper can be used
      as a master manipulator to control the surgical robot.

PMID- 29072505
TI  - Profiling of anthocyanidins against transcriptional activities of steroid and
      nuclear receptors.
AB  - The aim of current study was to evaluate the effect of the most common
      anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) on
      the transcriptional activity of steroid and nuclear receptors. The activities of
      steroid receptors - progesterone receptor (PR), estrogen receptor (ER), androgen
      receptor (AR), glucocorticoid receptor (GR), and nuclear receptors - vitamin D
      receptor (VDR), retinoid X receptor (RXR), retinoic acid receptor (RAR), pregnane
      X receptor (PXR), and thyroid receptor (TR) were assessed using either stable
      transfected luciferase gene reporter cell lines or transiently transfected cell
      lines. The cytotoxicity assays and gene reporter assays were performed after the
      24-h treatment of cells with increasing range of concentrations (10 nM to 50 uM)
      of selected anthocyanidins. The results of experiments indicate that none of the
      examined anthocyanidins in all tested concentrations caused remarkable changes of
      transcriptional activity of studied steroid receptors, but their increasing
      concentrations slightly inhibited transcriptional activity of nuclear receptors
      induced by model agonists.

PMID- 29072506
TI  - Deformable multi-modal registration using 3D-FAST conditioned mutual information.
AB  - PURPOSE: Mutual information (MI) has been a preferred choice of similarity
      measure for multi-modal image registration, but the accuracy and robustness of MI
      are not satisfactory as MI only considers the global intensity correlation while
      ignoring local and structural information. To address this problem, we combine MI
      with local and structural information. METHOD: We bring structural information
      extracted by a modified Accelerated Segment Test (FAST) algorithm into MI.
      Traditional FAST is transferred into 3 D for the first time, and the 3 D-FAST
      based structural information is added into MI as another channel, thereby
      incorporating spatial and geometric information with intensity information in the
      registration. RESULT: The robustness and accuracy of the proposed method were
      demonstrated in three experiments. The average registration errors of our method
      were 1.17, 1.33 and 1.20 compared to 1.47, 1.63 and 1.40 of LMI in T1-T2, T1-PD
      and T2-PD registration respectively. DISCUSSION: In this paper, we use the
      structural similarity computed by 3 D-FAST as the conditional information to
      encode spatial and geometric cues into LMI. In all of these three experiments,
      our method shows to be more robust and accurate than common registration methods
      based on information theory.

PMID- 29072509
TI  - Matthew Flinders Senior (1751-1802): Surgeon and 'man midwife'.
AB  - Until the eighteenth century, midwifery was the sole domain of women, but changes
      in medical science saw it appropriated by medical men and the 'man-midwife'
      emerged. This paper demonstrates the work of a man-midwife in a small English
      village in one year, 1775, using his accounts and correspondence. The man was
      Matthew Flinders Senior, 'surgeon and man-midwife' at Donington, Lincolnshire. He
      was the father of Captain Matthew Flinders, the famous navigator who mapped the
      coast line of Australia and who coined that name. Primary sources, published as a
      collection by the Lincoln Record Society, were used. Flinders Senior made a good
      living from his midwifery, charging rates commensurate with those charged by
      obstetricians today (with reduced costs for the poor). His descriptions of his
      practice show how midwifery was conducted in rural England during the development
      of medicine as a high-status profession. The paper uses data from one year to
      provide a snap shot of the work of a rural surgeon and man-midwife, but much more
      is available in the published collection, providing ready access for researchers
      who may like to pursue such work further.

PMID- 29072507
TI  - Grass pollen sublingual immunotherapy tablets provide long-term relief of grass
      pollen-associated allergic rhinitis and reduce the risk of asthma: findings from
      a retrospective, real-world database subanalysis.
AB  - BACKGROUND: We assessed real-world, long-term effectiveness of two marketed
      sublingual immunotherapy (SLIT) tablets for allergic rhinitis (AR), and their
      impact on allergic asthma (AA) onset/progression. METHODS: Retrospective,
      longitudinal German prescription database subanalysis of AR patients receiving 5-
      or 1-grass pollen SLIT tablets (n = 1,466/1,385), versus patients not using
      allergy immunotherapy (AIT) (n = 71,275). Primary endpoint: change over time in
      AR symptomatic medication prescriptions after treatment cessation; secondary
      endpoints: new asthma onset, and change over time in asthma medication
      prescriptions during treatment/follow-up periods. RESULTS: Mean number of AR
      medication prescriptions was significantly decreased during follow-up (of up to 6
      years) with both SLIT tablets versus the non-AIT group (p < 0.001). Over the full
      analysis period, proportions of patients with new-onset asthma were 8.8% (odds
      ratio: 0.676, p = 0.011), 10.3% (odds ratio: 0.720, p = 0.060) and 11.6% in the 5
      and 1-grass pollen SLIT tablet and non-AIT groups, respectively. For all
      treatment-analysis periods, both SLIT tablet groups were associated with fewer
      asthma medication prescriptions versus non-AIT controls. CONCLUSIONS: These
      findings confirm the real-world benefits of 5- and 1-grass-pollen SLIT tablets in
      slower AR progression, reduced risk of new asthma onset in the non-asthmatic
      population, and slower asthma progression in the asthmatic population.

PMID- 29072508
TI  - The aquaporin-4 water channel as a potential drug target in neurological
      disorders.
AB  - INTRODUCTION: Aquaporin-4 (AQP4) is a water transporting protein expressed at the
      plasma membrane of astrocytes throughout the central nervous system (CNS).
      Analysis of AQP4 knockout mice has suggested its broad involvement in brain water
      balance, neuroexcitation, glial scarring, neuroinflammation, and even
      neurodegenerative and neuropsychiatric disorders. Broad clinical utility of AQP4
      modulators has been speculated. Area covered: This review covers the biology of
      AQP4, evidence for its roles in normal CNS function and neurological disorders,
      and progress in AQP4 drug discovery. Expert opinion: Critical examination of
      available data reduces the lengthy potential applications list to AQP4 inhibitors
      for early therapy of ischemic stroke and perhaps for reduction of glial scarring
      following CNS injury. Major challenges in identification and clinical development
      of AQP4 inhibitors include the apparent poor druggability of AQPs, the many
      homologous AQP isoforms with broad tissue distribution and functions, technical
      issues with water transport assays, predicted undesired CNS and non-CNS actions,
      and the need for high blood-brain barrier permeation. To date, despite
      considerable effort, validated small-molecule AQP4 inhibitors have not been
      advanced. However, a biologic ('aquaporumab') is in development for neuromyelitis
      optica, an autoimmune inflammatory demyelinating disease where CNS pathology is
      initiated by binding of anti-AQP4 autoantibodies to astrocyte AQP4.

PMID- 29072510
TI  - Ameliorative effects of curcumin towards cyclosporine-induced genotoxic
      potential: an in vitro and in silico study.
AB  - Several studies documented the ameliorative effects of curcumin which plays a
      pivotal role in radical scavenging activities. It also participates in various
      cellular pathways and interacts with multiple targets. In the present study, we
      investigated the ameliorative effect of curcumin upon chromosomal genotoxicity
      induced by cyclosporine, an immunosuppressant, using in vitro approaches. A
      plausible mechanism of how curcumin mitigates the genotoxic implications of
      cyclosporine was ascertained using in silico tools. We observed that the curcumin
      reduces the genotoxic consequences made by cyclosporine upon cell cycle
      checkpoints and associated chromosomal/DNA manifestations. In addition, we
      presented the mechanistic details of curcumin interaction with various
      biomacromolecule types using docking experiments which showed that the possible
      radical scavenging activities can only be emerged by inducing the expression of
      antioxidant enzymes, supported by available experimental evidences. We anticipate
      that the induction of antioxidant enzymes by curcumin would activate Nrf2-Keap1
      pathway as the plausible mechanism to exert anti-inflammatory response as
      demonstrated in renal epithelial cells.

PMID- 29072511
TI  - Normative nasalance scores for Vietnamese-speaking children.
AB  - OBJECTIVE: The Nasometer is increasingly being used to complement auditory
      perceptual assessment of nasality. Nasalance scores which are obtained from the
      Nasometer vary across languages. Normative nasalance scores have been established
      for many languages but not for the Vietnamese language. The objective of this
      study was to obtain the normative nasalance scores for Vietnamese-speaking
      children. PARTICIPANTS: In this study, 102 healthy Vietnamese children speaking
      in the central regional dialect aged from 7 to 9 years (45 boys, 57 girls; mean
      age = 7.5 years) at a primary school in Hue, Vietnam participated. PROCEDURES:
      Three speech stimuli, which were specific for the Vietnamese language, were
      designed: oral stimuli (19 words and 18 sentences), oro-nasal stimuli (eight
      sentences) and nasal stimuli (seven sentences). The children were asked to repeat
      these stimuli after the examiner. The Nasometer II (model 6450) was used to
      obtain the nasalance scores. The procedure took about 10 minutes for each child.
      RESULTS: The mean nasalance scores and the standard deviation of each stimulus
      were: 13.1 +/- 5.8 (oral stimuli), 30.7 +/- 6.6 (oro-nasal stimuli) and 56.9 +/-
      9.2 (nasal stimuli). No significant differences between the genders were found.
      CONCLUSIONS: The normative nasalance scores provide essential reference
      information for clinicians who deal with nasalance disorders, especially patients
      with cleft palate. The nasalance scores in this study were established for
      Vietnamese children speaking in the central regional dialect and can be applied
      to both genders.

PMID- 29072512
TI  - Ibn Mandevaih Isfahani (949-983(?) AD), a physician from Isfahan's medical
      school.
AB  - There have arisen a number of prominent Iranian-Islamic physicians throughout the
      history of the fertile medicine landscape of Iran, some of whom are not very well
      known. Abu Ali Ahmad ibn Abd al-Rahman Mandevaih Isfahani (949-983(?) AD) was a
      great medical figure with scientific activities in the Hospital of Isfahan and al
      Adudi Hospital of Baghdad in the golden age of Iranian-Islamic history, culture,
      and civilization during the reign of the Buyid dynasty and Abbasid Caliphate. He
      was also a prominent physician during the reign of Adud al-Dawla Deylami (949-983
      AD). This present research has as its objectives the studying of the scientific
      life of ibn Mandevaih Isfahani and his works in this field. The works of this
      scientist and scholar reflect his skill and expertise in literature, philosophy,
      medicine, and medicine-related fields including ophthalmology and pharmacology.

PMID- 29072513
TI  - Bio-invasive ascidians in Ireland: A threat for the shellfish industry but also a
      source of high added value products.
AB  - In October 2016, a rapid assessment survey of ascidian species was conducted in
      shellfish farms at Killary Fjord, in the west of Ireland. Two non-indigenous
      solitary ascidians Ascidiella aspersa and Corella eumoyta were recorded for the
      first time in shellfish farms at this location. Both invasive ascidians have the
      potential to greatly reduce mussel production in Killary Fjord by competing with
      shellfish for food and habitat. Their high abundance also causes an increase in
      maintenance costs leading to economic losses for aquaculture farmers. Prompted by
      our finding of two invasive ascidians in Killary Fjord, we provide a brief review
      of the ecological role of ascidians and the potential of harnessing biomass from
      such invasive species for the production of high added value marine natural
      products.

PMID- 29072514
TI  - Effectiveness of Matricaria chamomilla (chamomile) extract on pain control of
      cyclic mastalgia: a double-blind randomised controlled trial.
AB  - Breast pain (mastalgia) often precedes menstrual period, which is of mild to
      moderate severity. This study was performed to determine the effectiveness of
      chamomile on pain control of cyclic mastalgia. This double-blind randomised
      controlled clinical trial was conducted on 60 patients with mastalgia referred to
      the breast clinic of an academic hospital, Mashhad University of Medical
      Sciences. The patients were randomly allocated into two groups: chamomile (n =
      30) and placebo (n = 30). Primary outcomes were: (1) assessment of the visual
      analogue scale (VAS) and (2) assessment of the breast pain chart (BPC) 8 weeks
      after initial intervention. All the participants were asked to take drops three
      times a day each time having five drops for two consecutive months. Significant
      decline was observed in both the groups (chamomile and placebo) after two months
      (p < .0001 and p = .048, respectively) compared to baseline and between two
      groups (p = .007). Chamomile was a well-tolerated, secure and effective drug for
      treating women with mild to moderate mastalgia. Impact statement What is already
      known on this subject: Breast pain (mastalgia) is a common chief complaint
      reported by many women. The 'cyclic' type, which usually occurs monthly prior to
      the onset of menstrual period, is of moderate severity. In 30% of the cases,
      mastalgia is severe and disturbs normal life, leading to sexual, physical, and
      social dysfunction as well as depression and anxiety. The cause of cyclical
      mastalgia is not known, but given the fact that it begins in the luteal phase, it
      can be caused by hormonal stimulation. A variety of therapies have been
      recommended. Such therapies include prescription of vitamin B2, B6, E and C, non
      steroidal anti-inflammatory drugs (NSAIDs), diuretics, thyroxin, progesterone,
      Tamoxifen, Danazol, Bromocriptine and plant extracts like vitexagnus castus,
      evening primrose oil (EPO). However, given the side effects of hormonal
      treatment, many women have developed a propensity towards the use of herbal
      medicine. What do the results of this study add: Chamomile presents a safe, well
      tolerated and effective treatment for women with moderate mastalgia. What are the
      implications of these finding for clinical practice and/or further research:
      Considering that Danazol, Bromocriptine and Tamoxifen are standard treatments for
      mastalgia, it would be helpful to carry out a trial study to compare the effect
      of chamomile extract versus standard treatments. The physicians can prescribe
      chamomile as a safe alternative treatment for mastalgia.

PMID- 29072516
TI  - The first female authors of the Journal of Urology.
AB  - Introduction In 1917, Alma Hiller became the first woman to publish in the
      Journal of Urology ( JU). Her contribution was followed by articles from Carol
      Beeler and Isabel Mary Wason. This study explores their careers and
      contributions. Methods We reviewed JU articles from 1917 to 1925 and identified
      Hiller, Beeler, and Wason as the first three women authors. Using public records,
      we obtained information of their educations and careers. Results Hiller
      demonstrated resilience in obtaining training and ultimately contributed to
      innovation in clinical chemistry. Beeler worked on research on metabolic
      physiology. Wason influenced both lab work and national policy. Conclusions For
      female scientists entering the workforce in the late 1800s/early 1900s, reception
      was contingent upon the acceptance of male colleagues. Despite these barriers,
      Hiller, Beeler, and Wason contributed to novel discoveries. Their most
      influential contributions remain their historic presence as early female
      researchers and the first female authors in JU.

PMID- 29072517
TI  - Improving vaccine coverage in adolescence and beyond.
AB  - High vaccine coverage is required to ensure population protection, including
      protection of those that cannot receive vaccines either due to contraindications
      or age. Despite this, some areas continue to report low vaccine coverage. Reasons
      for this may vary but can include factors such as difficulties accessing
      services, conflicting priorities and false contraindications or fear of potential
      side effects. Population groups with reported low vaccine coverage include
      pregnant women, adolescents and those aged 70-80 years and eligible to receive
      the shingles vaccine. The afternoon symposium included presentations from
      speakers each describing interventions for promoting vaccine uptake in these
      particular groups. Such interventions may include: * Ensuring effective
      leadership with clear aims for the delivery and on-going evaluation of the
      program * Providing health care workers with training and access to factually
      correct immunization resources * Offering a flexible service with vaccination in
      venues that are easy to access.

PMID- 29072518
TI  - Mary Barkas at the Maudsley: 1923-1927.
AB  - The Maudsley Hospital, reopened in January 1923, became the centre of British
      psychiatric research and achieved a world-wide reputation. At a time when women
      were rare in psychiatry, New Zealand-born Mary Barkas was the only woman (and
      psychoanalyst) among the first four psychiatrists appointed. This paper looks at
      her role in the early years at the Maudsley. The letters she wrote to her father,
      often on a daily basis, provide a unique insight to the earliest years of the
      hospital that was to have such an influence on British psychiatry. It is the only
      insider record we have of this crucial time. Barkas demonstrated her versatility
      in psychiatry and child psychiatry. She used psychoanalysis to treat her
      patients, receiving recognition from her colleagues. Her work in this field
      proved to be an exception as analysis was not practiced after she left the
      Maudsley. Her problem was the institutionalised prejudice against women in
      psychiatry, which caused her to leave. Her career was terminated at an early
      stage and her life took a puzzling turn after she returned to New Zealand in
      1933. We can remember Mary Barkas as a forgotten psychiatric pioneer whose life
      and work deserves to be more widely known and recognised.

PMID- 29072519
TI  - Determination of genetic variations in the genus Dryomys Thomas, 1906 (Rodentia:
      Gliridae) distributed in Turkey using NADH dehydrogenase 1 (ND1) gene.
AB  - Genetic diversity and phylogeny of Dryomys nitedula and Dryomys laniger from
      Turkey was described in the present study by using mitochondrial DNA NADH
      dehydrogenase 1 gene (ND1). Genetic variation in ND1 gene was determined by two
      model-based phylogenetic analyses and a network analysis revealed 27 haplotypes
      of D. nitedula constructing four main lineages (Thrace, Anatolia, North-eastern
      Anatolia and Savsat) that have non-overlapping geographic distributions and no
      shared haplotypes, but on the other hand, three haplotypes were detected in four
      samples of D. laniger from Turkey. It was determined that nucleotide diversity
      was low but haplotype diversity was high in D. laniger, whereas, D. nitedula has
      both high level of haplotype and nucleotide diversity. Characterization of Thrace
      lineage of D. nitedula with low nucleotide diversity and determination of the
      total nucleotide diversity of Anatolian lineages (Anatolia + North-eastern
      Anatolia+Savsat) to be approximately four times higher than that of Thrace
      lineage indicated that Anatolia may have served as a refuge for D. nitedula.
      Divergence times and high level of nucleotide differences between D. nitedula
      lineages showed that diversification of the lineages may have occurred before and
      during ice ages in Turkey, thought to be a refuge for post-glacial colonization
      and biodiversity resource of Europe. Additionally, estimated divergence times and
      calculated genetic distances yielded compatible results with the previous
      paleontological and genomic data for the diversification time of two species in
      the genus.

PMID- 29072520
TI  - Abstracts of papers presented at the 1st Italian-UK Platelet Meeting University
      of Bath, 7-8 September 2017.

PMID- 29072521
TI  - Orbital fat regeneration following hormonal treatment of metastatic breast
      carcinoma.
AB  - Enophthalmos in the setting of breast cancer metastatic to the orbit results
      primarily from the disease pathogenesis, or secondary to treatment effects.
      Orbital volume restoration and fat regeneration following endocrine treatment
      monotherapy has not been previously reported. A 76- year-old previously healthy
      female presented with progressive right enophthalmos secondary to metastatic
      lobular breast carcinoma. Treatment with an aromatase inhibitor (letrozole)
      resulted in tumor regression and orbital fat restoration with a corresponding
      improvement in orbital volume and enophthalmos on clinical exam. The patient is
      alive on continued letrozole with no progressive disease ten years after
      diagnosis. This case illustrates the resilience of orbital soft tissues and
      ability of orbital fat to regenerate in face of breast cancer metastasis. We
      hypothesize that endocrine monotherapy, and avoidance of radiation therapy,
      allowed for differentiation of remaining orbital stem cells, and facilitated the
      fat regenerative process.

PMID- 29072515
TI  - Interactions between metabolic, reward and cognitive processes in appetite
      control: Implications for novel weight management therapies.
AB  - Traditional models of appetite control have emphasised the role of parallel
      homeostatic and hedonic systems, but more recently the distinction between
      independent homeostatic and hedonic systems has been abandoned in favour of a
      framework that emphasises the cross talk between the neurochemical substrates of
      the two systems. In addition, evidence has emerged more recently, that higher
      level cognitive functions such as learning, memory and attention play an
      important role in everyday appetite control and that homeostatic signals also
      play a role in cognition. Here, we review this evidence and present a
      comprehensive model of the control of appetite that integrates cognitive,
      homeostatic and reward mechanisms. We discuss the implications of this model for
      understanding the factors that may contribute to disordered patterns of eating
      and suggest opportunities for developing more effective treatment approaches for
      eating disorders and weight management.

PMID- 29072523
TI  - Sir Winston Churchill's doctors on the Riviera 1949-1965: Herbert Robert Burnett
      Gibson (1885-1967) and Dafydd (David) Myrddin Roberts (1906-1977).
AB  - In May 1940, Sir Charles McMoran Wilson (later Lord Moran) was on the instigation
      of Lord Max Beaverbrook and Brendan Bracken, (both patients, then friends of
      Wilson) introduced to Winston Churchill. Thereafter, he remained Churchill's
      personal physician until Churchill's death. In his controversial book detailing
      Winston Churchill's health, Lord Moran refers briefly to two doctors resident in
      Monaco, who were involved in the management of Churchill's declining health from
      1949. One was Scottish, Herbert Robert Burnett Gibson and the other Welsh, Dafydd
      Myrddin Roberts. The military and civilian careers of these doctors are profiled
      here.

PMID- 29072522
TI  - Role of impulsivity and reward in the anti-obesity actions of 5-HT2C receptor
      agonists.
AB  - The selective 5-HT2C receptor agonist lorcaserin entered clinical obesity trials
      with the prevalent view that satiety was a primary mechanism of action.
      Subsequent Phase II and III trials demonstrated efficacy in terms of weight loss,
      although the overall effect size (~3% placebo-corrected change) is considered
      modest. Lorcaserin has been approved by the FDA for the treatment of obesity with
      lifestyle modification, but since its introduction in 2013 its sales are in
      decline, probably due to its overall modest effect. However, in some individuals,
      lorcaserin has a much more clinically significant effect (i.e. >10% placebo
      corrected change), although what common features, if any, define these high
      responders is presently unknown. In the present article we highlight the evidence
      that alternative mechanisms to satiety may contribute to the anti-obesity effect
      of lorcaserin, namely effects on constructs of primary and conditioned reward and
      impulsivity. This may better inform the clinical evaluation of lorcaserin (and
      any future 5-HT2C receptor agonists) to subgroups of obese subjects characterized
      by overeating due to maladaptive impulsivity and reward mechanisms. One such
      population might be individuals diagnosed with binge eating disorder.

PMID- 29072524
TI  - Acute side effects after consumption of the new synthetic cannabinoids AB
      CHMINACA and MDMB-CHMICA.
AB  - INTRODUCTION: In 2014, the "European Monitoring Centre for Drugs and Drug
      Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among
      these were indole- and indazole-based valine derivatives with a cyclohexylmethyl
      side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of
      SCs. METHODS: A prospective observational study of patients treated in emergency
      departments (EDs) after the intake of SCs was conducted. Clinical and laboratory
      data were combined and reported to a poison control centre. Serum and/or urine
      samples of ED patients were analyzed using LC-MS/MS. RESULTS: Forty four patients
      (39 male, five female, 12-48 years) were included. AB-CHMINACA (MDMB-CHMICA) was
      identified in 20 (19) serum samples, and in 21 (25) urine samples, respectively.
      In 19 of the cases, more than one SC was present. Other psychoactive substances
      (mainly amfetamines) were identified in seven cases, but in five out of these in
      urine samples only. Based on the Poison Severity Score, severity of poisoning was
      minor (4), moderate (31) or severe (9). Most frequently reported neuropsychiatric
      symptoms were CNS-depression (n = 21, 61%), disorientation (n = 20, 45%),
      generalized seizures (n = 12, 27%), combativeness (n = 8, 18%) and extreme
      agitation (n = 7, 16%). Duration of symptoms lasting 24 hours or longer occurred
      in 15 cases (34%). DISCUSSION: The prevalence of certain neuropsychiatric
      symptoms was higher in our study than in former reports after the intake of SCs
      of the aminoalkylindole-type (first generation) SCs. In addition, severe
      poisoning and duration of symptoms were also higher. CONCLUSIONS: In this study,
      the valine derivative AB-CHMINACA and the tert-leucine derivative MDMB-CHMICA
      ("third generation of SCs") seem to be associated with more severe clinical
      toxicity than was previously reported in patients exposed to earlier generation
      SCs such as JWH-018. However, this observation needs to be confirmed with a
      larger cohort of patients with analytically confirmed abuse of third generation
      SCs. The rapid turnover of SCs on the drug market together with the occurrence of
      SCs such as AB-CHMINACA and MDMB-CHMICA is alarming, especially because of the
      unexpectedly high frequency of neuropsychiatric symptoms.

PMID- 29072525
TI  - Evaluation of epigallocatechin gallate and epicatechin gallate effects on
      acrylamide-induced neurotoxicity in rats and cytotoxicity in PC 12 cells.
AB  - The neurotoxicity of acrylamide (ACR) monomer occurs through different mechanisms
      such as oxidative stress. Epigallocatechin gallate (EGCG) and epicatechin gallate
      (ECG) are green tea catechins which are known as powerful antioxidants. In this
      study, we examined the possible protective effects of ECG and EGCG on ACR
      neurotoxicity in both in-vitro and in-vivo models. PC12 cells were exposed to
      different concentrations of ECG and EGCG. After 24 and 48 hours, ACR was added to
      the cells (IC50 = 4.85 mM) and cell viability was measured through MTT assay
      after 24 hours. Male Wistar rats were pretreated with ECG, EGCG (10, 20 and 40
      mg/kg, i.p) and vitamin E (200 IU/kg i.p.) for 3 days. Afterwards they were
      treated with ACR (50 mg/kg, i.p.) for 11 days. After the treatment period, gait
      score examination was performed and molondialdehyde (MDA) and reduced glutathione
      (GSH) were measured in cerebral cortex. ACR reduced the cell viability in a
      concentration-dependent manner. Both ECG and EGCG (20 MUM) showed inhibitory
      effects on ACR cytotoxicity. ACR significantly induced gait abnormalities,
      decreased GSH level and increased lipid peroxidation in cerebral cortex. ECG and
      EGCG (20 mg/kg) improved all ACR toxic effects. Although the food intake was
      increased in pretreated groups compared to the ACR-treated group, intensive
      weight loss was observed due to the green tea's different weight loss mechanisms.
      ECG and EGCG inhibited the cytotoxicity of ACR in PC12 cells and increased GSH
      level and decreased lipid peroxidation in rat cerebral cortex.

PMID- 29072527
TI  - William Osler and the "fixed period" of creativity.
AB  - In 1905, William Osler was the pre-eminent physician in American medical circles
      but was unknown to the general public. The latter suddenly learned of him through
      damning newspaper accounts of his address announcing his retirement from the
      Johns Hopkins Medical School. In it Osler mentioned two "fixed ideas" he held-(1)
      that most major advances in civilization have been made by men under age 40 (the
      "fixed period") and (2) that those over 60 should retire because they create
      little of significance and sometimes stifled the initiatives of younger
      colleagues. He highlighted the second idea with a Victorian novel describing a
      mythical society which chloroformed men at age 60. He never imagined that this
      literary allusion would be taken as a serious solution for his second idea.
      However, countless newspaper articles ridiculed the first and condemned him for
      the second. Scurrilous press attacks on him continued for several months and
      resurfaced occasionally thereafter. The extent of the public approbation can also
      be found in poems and stories linking him with euthanasia. Also discussed here
      are the sources of Osler's equanimity in the face of such public derision and the
      inner drives which accounted for over 1300 publications by him-nearly half of
      which were composed after age 40.

PMID- 29072528
TI  - Discrimination, Subjective Wellbeing, and the Role of Gender: A Mediation Model
      of LGB Minority Stress.
AB  - The present study examined the link between discrimination and the three
      components of subjective wellbeing (positive and negative affect and life
      satisfaction) among a cisgender sample of lesbian, gay, and bisexual (LGB)
      adults. Specifically, we investigated internalized homonegativity and
      expectations of rejection as potential mediators of the links between
      discrimination and subjective wellbeing among a sample of 215 participants.
      Results from our structural equation model demonstrated a strong, positive direct
      link between discrimination and negative affect. Discrimination also had small,
      negative indirect effects on life satisfaction through our two mediators.
      Interestingly, neither discrimination nor our two mediators were related with
      positive affect, demonstrating the need for future research to uncover potential
      buffers of this link. Finally, our model evidenced configural, metric, and scalar
      invariance, suggesting that our model applies well for both women and men.
      Practical implications and future directions for research are discussed.

PMID- 29072529
TI  - Cognitive processes in spatial mapping: Evidence from a developmental spatial
      deficit.
AB  - We report a case study of an adolescent girl (N.K.Y.) with a developmental
      deficit affecting spatial processing. In a simple spatial mapping task, N.K.Y.
      shows a striking dissociation: She succeeds in one variant of the experiment in
      which the stimuli are objects, but struggles in a structurally identical task
      with people as stimuli. We present evidence that this dissociation stems from a
      tendency to automatically adopt the spatial perspective of other people, but not
      objects-a phenomenon also observed in neurotypical individuals. When adopting
      another person's perspective, N.K.Y. imagines herself in the other's position,
      representing the other's left and right as if it were her own. N.K.Y.'s deficit
      in relating left-right information to her own body then disrupts her performance.
      Our results shed light on the nature of N.K.Y.'s deficit as well as the cognitive
      operations involved in spatial perspective taking.

PMID- 29072530
TI  - A "Different Economy of Bodies and Pleasures"?: Differentiating and Evaluating
      Sex and Sexual BDSM Experiences.
AB  - This study examines how BDSM participants understand sexual experiences. Data are
      drawn from 32 in-depth, semistructured interviews and discussion-board threads
      from a large BDSM community Web site. The analysis suggests that many BDSM
      participants perceive sexual BDSM experiences as not only significantly different
      from but also better than mainstream or "vanilla" sex. Three primary
      differentiation mechanisms are identified. First, BDSM participants constructed
      sex as requiring genital contact, while framing sexual BDSM as creating sexual
      fulfillment not requiring normative indicators of sexual experiences (e.g.,
      orgasm). Second, participants constructed sexual BDSM as centered on emotional
      and mental experiences, while perceiving sex as being centered on physical
      experiences. Third, participants perceived sexual BDSM experiences as
      facilitating deeper interpersonal connections than those available in sex.
      Importantly, these mechanisms serve not only a differentiating but also an
      evaluative function. Most participants in this study reported a strong preference
      for sexual BDSM over sex.

PMID- 29072526
TI  - Rab GTPases in cilium formation and function.
AB  - Cilia are microtubule-based organelles extending from a basal body at the surface
      of eukaryotic cells. Cilia regulate cell and fluid motility, sensation and
      developmental signaling, and ciliary defects cause human diseases (ciliopathies)
      affecting the formation and function of many tissues and organs. Over the past
      decade, various Rab and Rab-like membrane trafficking proteins have been shown to
      regulate cilia-related processes such as basal body maturation, ciliary axoneme
      extension, intraflagellar transport and ciliary signaling. In this review, we
      provide a comprehensive overview of Rab protein ciliary associations, drawing on
      findings from multiple model systems, including mammalian cell culture, mice,
      zebrafish, C. elegans, trypanosomes, and green algae. We also discuss several
      emerging mechanistic themes related to ciliary Rab cascades and functional
      redundancy.

PMID- 29072531
TI  - Solitude as an Approach to Affective Self-Regulation.
AB  - In this research, we showed that solitude generally has a deactivation effect on
      people's affective experiences, decreasing both positive and negative high
      arousal affects. In Study 1, we found that the deactivation effect occurred when
      people were alone, but not when they were with another person. Study 2 showed
      that this deactivation effect did not depend on whether or not the person was
      engaged in an activity such as reading when alone. In Study 3, high-arousal
      positive affect did not drop in a solitude condition in which participants
      specifically engaged in positive thinking or when they actively chose what to
      think about. Finally, in Study 4, we found that solitude could lead to relaxation
      and reduced stress when individuals actively chose to be alone. This research
      thus shed light on solitude effects in the past literature, and on people's
      experiences when alone and the different factors that moderate these effects.

PMID- 29072533
TI  - Endoscopic Evaluation and Treatment of Postoperative Bariatric Surgery
      Complications.
AB  - The number of patients undergoing bariatric surgery continues to increase. The
      American Society for Metabolic and Bariatric Surgery (ASMBS) estimates the number
      of bariatric surgical procedures performed increased from 158 000 in 2011 to 190
      000 in 2015. Concurrently, the incidence of postoperative complications specific
      to bariatric patients will inevitably increase as well. Endoscopic evaluation of
      postoperative bariatric patients and endoscopic interventions are rapidly
      evolving. We present a review of the postoperative anatomy of bariatric patients,
      what complications to expect, and treatment options.

PMID- 29072534
TI  - Susceptibility of Representative Great Lakes Fish Species to the North Carolina
      Strain of Spring Viremia of Carp Virus (SVCV).
AB  - Spring viremia of carp virus (SVCV) is a notifiable pathogen of the World
      Organization of Animal Health. Since SVCV was isolated in Lake Ontario in 2007,
      concern has grown about its spread in the Great Lakes basin and its potential
      negative impacts on fish species of importance in stock enhancement programs
      basinwide. The susceptibility of representative fish species from the families
      Cyprinidae (Fathead Minnow Pimephales promelas, Golden Shiner Notemigonus
      crysoleucas, Spotfin Shiner Cyprinella spiloptera, and Creek Chub Semotilus
      atromaculatus), Centrarchidae (Largemouth Bass Micropterus salmoides), Percidae
      (Walleye Sander vitreus), Salmonidae (Rainbow Trout Oncorhynchus mykiss), and
      Esocidae (Muskellunge Esox masquinongy) to SVCV was evaluated by experimental
      infection under laboratory conditions. Morbidity and mortality were recorded, and
      virus re-isolation, seminested reverse transcription PCR, and histopathological
      assessments were performed. Using intraperitoneal (i.p.) injection, Fathead
      Minnows and Golden Shiners were highly susceptible to SVCV (40-70% mortality).
      All dead or moribund and apparently healthy surviving Fathead Minnows and Golden
      Shiners were SVCV positive. The SVCV was also detected in challenged but healthy
      Spotfin Shiners (30%) and Creek Chub (5%). However, noncyprinid species exhibited
      no morbidity or mortality and were free of SVCV following an observation period
      of 30 d. In a follow-up experimental challenge, Fathead Minnows and Golden
      Shiners were SVCV challenged at 103 and 105 PFU/mL by means of waterborne
      immersion. After immersion, Fathead Minnows and Golden Shiners exhibited
      characteristic SVCV disease signs, but mortality was less (30% and 10% mortality,
      respectively) than that in fish with i.p. injections. The SVCV was detected in
      all mortalities and a subset of healthy Fathead Minnows and Golden Shiners.
      Necrotic changes were observed in the kidneys, liver, spleen, ovaries, and heart,
      and other histopathological lesions also occurred. These findings suggest that
      two of the four cyprinids tested are susceptible to SVCV-induced disease and that
      all four can act as potential carriers of SVCV in the Laurentian Great Lakes.
      Received January 11, 2017; accepted July 17, 2017.

PMID- 29072532
TI  - Antibacterial efficacy of silver nanoparticles and ethyl acetate's metabolites of
      the potent halophilic (marine) bacterium, Bacillus cereus A30 on multidrug
      resistant bacteria.
AB  - Bacteria are generally responsible for the prevalence of several diseases and
      pathogenic bacteria are showing increasing resistance to different
      antibacterials. During the present study an extremophilic bacterium-A30 isolated
      from the marine waters was characterized and evaluated against four multi-drug
      resistant (MDR) pathogens, viz; Methicillin-resistant Staphylococcus aureus
      (MRSA), Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The
      sensitivity pattern of the selected pathogens was tested with 31 antibiotics.
      Among the 47 marine microbial extracts tested on 4-MDR pathogens viz: Methicillin
      resistant Staphylococcus aureus (MRSA), E. coli, K. pneumoniae and P. aeruginosa,
      only our strain A30 strain exhibited highest efficacy. This strain was
      subsequently subjected to 16S rDNA sequencing which confirmed its allocation as
      Bacillus cereus. Silver nanoparticle (AgNPs) synthesis and ethyl acetate
      extraction were performed using the supernatant of B. cereus. The synthesized
      AgNPs were characterized by UV-Visible, Fourier-transform infra-red (FT-IR), X
      ray diffraction (XRD), Field emission-scanning electron microscopy (FE-SEM),
      energy dispersive X-ray spectroscopy (EDX), and Zeta potential analyses. The
      presence of functional groups and 13 bioactive components in the ethyl acetate
      extract were analyzed using FT-IR and gas chromatography-mass spectrometry (GC
      MS). The synthesized of AgNPs and the ethyl acetate extract showed preponderant
      activity against P. aeruginosa and MRSA, respectively. The effects of AgNPs were
      significant when compared to ethyl acetate extract. Therefore, the halophilic
      bacterium, B. cereus mediated AgNPs could provide antibacterial applications in
      the biomedical industries.

PMID- 29072535
TI  - Americans' Gender Attitudes at the Intersection of Sexual Orientation and Gender.
AB  - Extensive research on differences in women's and men's gender attitudes and more
      recent work on sexual orientation differences in these and other social attitudes
      have overlooked the potential intersection between gender and sexual orientation
      in predicting Americans' gender attitudes. I use data from the 2012 American
      National Election Survey 2012 to investigate differences in views on gender
      roles, gender discrimination and inequality, and abortion among lesbian and
      bisexual women, gay and bisexual men, heterosexual women, and heterosexual men.
      The results suggest that heterosexual men hold the most conservative views on
      gender, while lesbian and bisexual women are most conscious of gender
      discrimination and inequality. These differences are partially explained by LGB
      Americans' liberal political ideology and heightened awareness of homophobic
      discrimination-two mechanisms that are also gendered. I conclude by arguing that
      the intersection between sexual orientation and gender produces unique lived
      experiences that, in turn, produce gendered sexual orientation gaps in
      worldviews.

PMID- 29072536
TI  - Hepatitis B Outbreak Among Men Who Have Sex with Men in the Autonomous Province
      of Vojvodina, Serbia.

PMID- 29072537
TI  - Sleep, training load and performance in elite female gymnasts.
AB  - Training load (TL) and recovery should be in optimal balance to obtain maximal
      performance gains. We aimed to study sleep as a recovery technique and its
      relationship with TL and performance in elite athletes. Twenty-six elite female
      artistic gymnasts were divided into an under 13 (n = 6), an under 14 (n = 6), a
      junior (n = 7; 14-15y) and a senior (=World Championship (WC) competitors, n = 7;
      >=16y) category. Sleep, through sleep logs, and training parameters, using the
      session Rate of Perceived Exertion (sRPE) scale, were monitored to calculate
      total sleep time (TST), sleep efficiency (SE), TL, monotony and strain.
      Performance of WC competitors was evaluated through coach and WC qualification
      ranking. For the entire group, TST (effect sizes (ES) = -1.12, confidence
      intervals (CI) = -60:-47, P < .05) and SE (ES = -0.13, CI = -1.40:-0.10, P =
      .022) were shorter during week than weekend nights. TST and SE were highest in
      youngest gymnasts (P < .05). TL was lowest in under 13 and senior gymnasts (P <
      .05), while TL, monotony and strain were highest in junior gymnasts (P < .05). A
      negative regression was found between TST and TL the day after, while higher TL
      also led to lower TST the following night (P < .001). For the WC competitors, TST
      the night before the qualifications was shorter than the mean TST of the WC
      period (ES = -0.95, CI = -170:24, P = .030). TST correlated with coach ranking (r
      = -0.857, P = .014). Higher TL correlated with worse WC (r = 0.829, P = .042) and
      coach (r = 0.893, P = .007) ranking. This research in elite gymnasts indicated
      associations between decreased TST, augmented TL and inferior performance.
      Optimizing sleep and TL may therefore represent strategies to enhance
      performance.

PMID- 29072538
TI  - Senior Services that Support Housing First in Metro Vancouver.
AB  - Housing First is a model and philosophy for housing homeless people in immediate
      and permanent housing. In order to implement and deliver Housing First, research
      is essential to understand the system of support services as they currently
      exist. Guided by principles of community-based participatory research, this paper
      presents the findings from a senior-focused deliberative dialogue workshop in
      Metro Vancouver, Canada. Participants (16 service providers and 1 service
      recipient) identified services and resources available to support seniors in
      maintaining housing and barriers and facilitators for accessing services.
      Broadly, data were organized into seven themes: (1) Housing; (2) Home support;
      (3) Transportation; (4) Information availability, accessibility, and navigation;
      (5) Cultural diversity; (6) Discrimination; and (7) Funding and financial
      support. Results found that affordable housing that adapts to changing health
      conditions, income supports, health services, homecare, transportation, and
      culturally appropriate and nondiscriminatory informational resources are among
      the supports most needed for persons as young as 50 years old to succeed under
      the Housing First model in Metro Vancouver. Barriers to Housing First service
      provision, including rigid eligibility criteria for chronically and episodically
      homeless, should be revised to better support the growing number of older adults
      who are newly entering homelessness in Metro Vancouver.

PMID- 29072539
TI  - Coordination Impairments Are Associated With Falling Among Older Adults.
AB  - : Background/Study Context: Approximately one third of older adults over the age
      of 65, and over 40% of those over 80 years, fall each year, leading to fractures,
      morbidity, and mortality. Annual direct medical costs due to falls in the United
      States are approximately $19.2 billion. The identification of new treatable risk
      factors for falls has the potential to advance their prevention and
      rehabilitation. METHODS: A cross-sectional study of 127 community-dwelling adults
      aged 67-99 years was conducted. An electronic gait walkway was used to assess
      gait coordination, measured as the Phase Coordination Index during normal speed
      walking. A motion capture system was used to assess rhythmic interlimb antiphase
      ankle coordination, measured as the standard deviation of ankle relative phase.
      Having fallen in the previous year was self-reported retrospectively. Odds ratios
      for falling as a function of coordination quartiles were determined using
      multivariable logistic regression. RESULTS: Adjusting for age, sex, body mass
      index, number of chronic conditions, Mini-Mental State Examination score, gait
      speed, and the variability of step length, time, and width, the odds ratios for
      falling based upon being in the 4th (the poorest) quartiles of gait or ankle
      coordination were 5.5 (95% confidence interval [CI]: 1.2-24.7) and 8.2 (95% CI:
      2.2-31.3), respectively, and 3.7 (95% CI: 1.0-13.8) for the 3rd quartile of gait
      coordination, compared with the best (the 1st) coordination quartiles. Similar
      results were found in regression without adjustment for gait characteristics.
      CONCLUSION: The results support the hypothesis that impaired gait and rhythmic
      interlimb ankle coordination are associated with a history of falls in the past
      year. Prospective longitudinal research is needed to determine the possible
      direction of causality between falls and impaired coordination.

PMID- 29072540
TI  - Cognitive performance and aphasia recovery.
AB  - Objectives This study assessed cognitive performance of subjects with aphasia
      during the acute stage of stroke and evaluated how such performance relates to
      recovery at 3 months. Materials & methods Patients with aphasia following a left
      hemisphere stroke were evaluated during the first (baseline) and the fourth-month
      post onset. Assessment comprised non-verbal tests of attention/processing speed
      (Symbol Search, Cancelation Task), executive functioning (Matrix Reasoning, Tower
      of Hanoi, Clock Drawing, Motor Initiative), semantic (Camel and Cactus Test),
      episodic and immediate memory (Memory for Faces Test, 5 Objects Memory Test, and
      Spatial Span. Recovery was measured by the Token Test score at 3 months. The
      impact of baseline performance on recovery was evaluated by logistic regression
      adjusting for age, education, severity of aphasia and the Alberta Stroke Program
      Early CT (ASPECT) score. Results Thirty-nine subjects (with a mean of 66.5 +/-
      10.6 years of age, 17 men) were included. Average baseline cognitive performance
      was within normal range in all tests except in memory tests (semantic, episodic
      and immediate memory) for which scores were <=-1.5sd. Subjects with poor aphasia
      recovery (N = 27) were older and had fewer years of formal education but had
      identical ASPECT score compared to those with favorable recovery. Considering
      each test individually, the score obtained on the Matrix Reasoning test was the
      only one to predict aphasia recovery (Exp(B)=24.085 p = 0.038). Conclusions The
      Matrix Reasoning Test may contribute to predict aphasia recovery. Cognitive
      performance is a measure of network disruption but may also indicate the
      availability of recovery strategies.

PMID- 29072541
TI  - Temporomandibular clinical exploration in Italian adolescents.
AB  - OBJECTIVE: This study investigated the prevalence of the signs and symptoms of
      temporomandibular disorders (TMD) among Italian adolescents. METHODS: The data
      were recorded from 567 subjects (246 males and 321 females; age range 11-19
      years), grouped according to age and molar class relationship. RESULTS: Forty
      four point one percent of subjects showed at least one sign or symptom of TMD,
      which were significantly more frequent in the 16-19 year-old group (52.9%) in
      respect to the 11-15 year-old group (39.8%) (chi2 = 8.78; p = 0.003). Signs
      and/or symptoms were about 1.6 times more frequent in subjects with Class II/1
      malocclusion (chi2 = 13.3, p = 0.0003), mostly for TMJ sounds (chi2 = 1.444; p =
      0.036). Myalgia was more frequent in females than in males (chi2 = 3.882; p =
      0.049). CONCLUSION: TMD signs and/or symptoms among Italian adolescents seem
      diffused (44.1%). Therefore, all adolescents should be screened thorough medical
      history and clinical examination.

PMID- 29072542
TI  - A critical review of hearing-aid single-microphone noise-reduction studies in
      adults and children.
AB  - PURPOSE: Single-microphone noise reduction (SMNR) is implemented in hearing aids
      to suppress background noise. The purpose of this article was to provide a
      critical review of peer-reviewed studies in adults and children with
      sensorineural hearing loss who were fitted with hearing aids incorporating SMNR.
      METHOD: Articles published between 2000 and 2016 were searched in PUBMED and
      EBSCO databases. RESULTS: Thirty-two articles were included in the final review.
      Most studies with adult participants showed that SMNR has no effect on speech
      intelligibility. Positive results were reported for acceptance of background
      noise, preference, and listening effort. Studies of school-aged children were
      consistent with the findings of adult studies. No study with infants or young
      children of under 5 years old was found. Recent studies on noise-reduction
      systems not yet available in wearable hearing aids have documented benefits of
      noise reduction on memory for speech processing for older adults. CONCLUSIONS:
      This evidence supports the use of SMNR for adults and school-aged children when
      the aim is to improve listening comfort or reduce listening effort. Future
      research should test SMNR with infants and children who are younger than 5 years
      of age. Further development, testing, and clinical trials should be carried out
      on algorithms not yet available in wearable hearing aids. Testing higher
      cognitive level for speech processing and learning of novel sounds or words could
      show benefits of advanced signal processing features. These approaches should be
      expanded to other populations such as children and younger adults. Implications
      for rehabilitation The review provides a quick reference for students and
      clinicians regarding the efficacy and effectiveness of SMNR in wearable hearing
      aids. This information is useful during counseling session to build a realistic
      expectation among hearing aid users. Most studies in the adult population suggest
      that SMNR may provide some benefits to adult listeners in terms of listening
      comfort, acceptance of background noise, and release of cognitive load in a
      complex listening condition. However, it does not improve speech intelligibility.
      Studies that examined SMNR in the paediatric population suggest that SMNR may
      benefit older school-aged children, aged between 10 and 12 years old. The
      evidence supports the use of SMNR for adults and school-aged children when the
      aim is to improve listening comfort or reduce listening effort.

PMID- 29072543
TI  - The General Factor of Personality and Character: A Reanalysis.
AB  - Using data from the Texas Twin Project, it was recently reported that 7 measures
      of character covaried to the extent that they formed a general factor of
      character (Tucker-Drob, Briley, Engelhardt, Mann, & Harden, 2016 ). In turn the
      relationship between the general factor of character and the Big Five personality
      traits were examined. It was found that personality was associated with the
      general factor of character primarily through the traits of conscientiousness and
      openness. For several reasons we propose that a more accurate interpretation of
      the data is that a Big Five personality traits form a general factor of
      personality, and that the relationship between the general character factor and
      personality is primarily through the general factor of personality. The results
      lend some support to this contention and are discussed in relation to the growing
      interest in covariation among multiple personality traits.

PMID- 29072544
TI  - A narrative review of the safety concerns of deprescribing in older adults and
      strategies to mitigate potential harms.
AB  - INTRODUCTION: As with prescribing or continuing medications, deprescribing brings
      with it the potential for harm as well as benefit. Uncertainty and avoidance of
      harm has been reported as a barrier to deprescribing in practice and may
      contribute to continuation of inappropriate medications. Areas covered: This
      narrative review covers four main safety concerns/potential harms of
      deprescribing in older adults: adverse drug withdrawal events, return of medical
      condition(s), reversal of drug-drug interactions and damage to the doctor-patient
      relationship. These are discussed in relation to medications in general, with
      some examples of medication classes used to illustrate the potential safety
      concerns. The majority of these harms can be minimized or even prevented by using
      a patient-centered, structured deprescribing process with planning, tapering and
      close monitoring during, and after medication withdrawal. Expert opinion: More
      research is needed into the safety concerns of deprescribing, however, avenues
      exist during drug development and post-marketing surveillance to gain knowledge
      on this topic. Questions remain about when it is suitable to discontinue certain
      medications/medication classes and there is uncertainty about the harms and
      benefits of both medication continuation and discontinuation in complex older
      adults.

PMID- 29072545
TI  - Comparison of seating, powered characteristics and functions and costs of
      electrically powered wheelchairs in a general population of users.
AB  - PURPOSE: To profile and compare the seating and powered characteristics and
      functions of electrically powered wheelchairs (EPWs) in a general user population
      including equipment costs. METHOD: Case notes of adult EPW users of a regional
      NHS service were reviewed retrospectively. Seating equipment complexity and type
      were categorized using the Edinburgh classification. Powered characteristics and
      functions, including control device type, were recorded. RESULTS: 482 cases were
      included; 53.9% female; mean duration EPW use 8.1 years (SD 7.4); rear wheel
      drive 88.0%; hand joystick 94.8%. Seating complexity: low 73.2%, medium 18.0%,
      high 8.7%. Most prevalent diagnoses: multiple sclerosis (MS) 25.3%, cerebral
      palsy (CP) 18.7%, muscular dystrophy (8.5%). Compared to CP users, MS users were
      significantly older at first use, less experienced, more likely to have mid-wheel
      drive and less complex seating. Additional costs for muscular dystrophy and
      spinal cord injury users were 3-4 times stroke users. CONCLUSIONS: This is the
      first large study of a general EPW user population using a seating
      classification. Significant differences were found between diagnostic groups;
      nevertheless, there was also high diversity within each group. The differences in
      provision and the equipment costs across diagnostic groups can be used to improve
      service planning. Implications for Rehabilitation At a service planning level,
      knowledge of a population's diagnostic group and age distribution can be used to
      inform decisions about the number of required EPWs and equipment costs. At a user
      level, purchasing decisions about powered characteristics and functions of EPWs
      and specialised seating equipment need to be taken on a case by case basis
      because of the diversity of users' needs within diagnostic groups. The additional
      equipment costs for SCI and MD users are several times those of stroke users and
      add between 60 and 70% of the cost of basic provision.

PMID- 29072547
TI  - Serum concentrations of Ang-2 and Flt-1 may be predictive of pregnancy outcome in
      women with pregnancies of uncertain viability: a phase I exploratory prognostic
      factor study.
AB  - The aim of this study was to determine whether serum concentrations of Ang-1, Ang
      2, Flt-1, IL-15 and/or TRAIL can be used to predict outcome in women with
      pregnancies of uncertain viability (PUVs). Women presenting to the Early
      Pregnancy Unit at the Queen's Medical Centre in Nottingham between 17.06.14 and
      01.09.15 were prospectively recruited. Serum concentrations of Ang-1, Ang-2, Flt
      1, IL-15 and TRAIL were measured in women with PUVs. Women were followed-up
      according to departmental protocols until viability was determined. Biomarker
      concentrations were correlated with pregnancy outcome. Ninety-four PUVs were
      studied, of which 61 (64.9%) were subsequently proven to be viable. There were
      statistically significant (p < .01), linear (p-valuetrend <.01) associations
      between Ang-2 and Flt-1 concentrations and pregnancy viability such that women
      with lower concentrations were significantly more likely to have viable
      pregnancies than women with higher concentrations. In conclusion, Ang-2 and Flt-1
      may be useful in predicting outcome in women with PUVs. Impact statement What is
      already known on this subject: Predicting outcome in women with pregnancies of
      uncertain viability (PUVs) is challenging. There is currently no accurate and
      reliable method. All PUVs need to be followed-up until a definitive diagnosis of
      either a viable or non-viable pregnancy can be made. This takes time, utilises
      limited resources and generates significant anxiety. Recent studies have
      demonstrated serum concentrations of Ang-1, Ang-2, Flt-1, IL-15 and TRAIL in
      viable pregnancies are significantly different to those in non-viable or ectopic
      pregnancies. What the results of this study add: The results from this
      prospective study of 94 women with PUVs suggest that serum concentrations of Ang
      2 and Flt-1 may be able to predict pregnancy viability in cases of uncertainty.
      Women with PUVs and low concentrations of Ang-2 or Flt-1 are significantly more
      likely to have viable pregnancies than women with high concentrations. What the
      implications are of these findings for clinical practice and/or further research:
      Evidence from multiple studies is necessary to appreciate the discriminating
      ability of these prognostic factors. Rapid clinical adoption in the absence of
      such evidence may lead to wasted resources. If our findings are confirmed,
      however, these biomarkers, either alone or as part of a prognostic model, may be
      capable of accurately predicting pregnancy outcome in cases of uncertainty. This
      would reduce the strain on limited resources and alleviate anxiety for women.

PMID- 29072548
TI  - Isolation of mutants with abnormal petal epidermal cell morphology.
AB  - Plants consist of many different cell types with specific shapes optimized for
      their particular functions. For example, most flowering plants have conically
      shaped epidermal cells on the upper surface of their petals that are important
      for pollinator attraction. The control of cell morphology in organs such as roots
      and leaves has been extensively studied, but much less is known about the genes
      that promote conical expansion of petal epidermal cells. We have developed a
      technique to rapidly assay the morphology of conical petal epidermal cells, and
      we employed this method in an unbiased genetic screen to identify mutants that
      alter the development of these cells. Mutants isolated in this screen affected
      cell shape, cell size, cuticle synthesis, and cellular chirality. This approach
      allowed for the identification of novel cellular components that are critical for
      the morphology of conical petal cells, and demonstrates the usefulness of petal
      epidermal cells as a model system for studying cellular morphogenesis.

PMID- 29072549
TI  - Model selection based on combined penalties for biomarker identification.
AB  - The growing role of targeted medicine has led to an increased focus on the
      development of actionable biomarkers. Current penalized selection methods that
      are used to identify biomarker panels for classification in high-dimensional
      data, however, often result in highly complex panels that need careful pruning
      for practical use. In the framework of regularization methods, a penalty that is
      a weighted sum of the L1 and L0 norm has been proposed to account for the
      complexity of the resulting model. In practice, the limitation of this penalty is
      that the objective function is non-convex, non-smooth, the optimization is
      computationally intensive and the application to high-dimensional settings is
      challenging. In this paper, we propose a stepwise forward variable selection
      method which combines the L0 with L1 or L2 norms. The penalized likelihood
      criterion that is used in the stepwise selection procedure results in more
      parsimonious models, keeping only the most relevant features. Simulation results
      and a real application show that our approach exhibits a comparable performance
      with common selection methods with respect to the prediction performance while
      minimizing the number of variables in the selected model resulting in a more
      parsimonious model as desired.

PMID- 29072546
TI  - Socioeconomic inequality in Hepatitis B vaccination of rural adults in China.
AB  - Hepatitis B (HB) vaccination is the most effective way to prevent HB virus
      infection. While measures taken to control the prevalence of HB have achieved
      significant results, HB prevalence in rural China among adults remains
      problematic. This study sheds new light on the determinants of HB vaccine uptake
      and its inequality according to socioeconomic status in rural areas of China. We
      interviewed 22,283 adults, aged 18-59 years, from 8444 households, in 48 villages
      from 8 provinces. Vaccination status was modeled by using two logistic models:
      whether take at least one HB vaccine and whether to complete the entire
      vaccination regime. The Erreygers' concentration index ([Formula: see text]) was
      used to quantify the degree of inequality and the decomposition approach was used
      to uncover the determinants of inequality in vaccine uptake. We found that the
      coverage rate of HB vaccination is 20.2%, and the completion rate is 16.0%. The
      [Formula: see text] of at least one dose (0.081) and three doses (0.076) revealed
      a substantial pro-rich inequality. Income contributed the largest percentage to
      HB vaccination inequalities (52.17% for at least one dose and 52.03% for complete
      vaccinations). HB awareness was another important cause of inequality in HB
      vaccination (around 30%). These results imply that rich had a greater tendency to
      vaccinate and inequality favouring the rich was almost equal for the complete
      three doses. While the factors associated with HB vaccination uptake and
      inequalities were multifaceted, income status and HB awareness were the main
      barriers for the poor to take HB vaccine by adults in rural China.

PMID- 29072550
TI  - Association of glutathione S-transferases M1, P1 and T1 variations and risk of
      late-onset Alzheimer's disease.
AB  - OBJECTIVE: Late-onset Alzheimer's disease (AD) is a genetically heterogeneous
      neurodegenerative disorder. Associations of the glutathione S-transferases (GSTs)
      polymorphisms with the risk factors for AD have not been definitely confirmed. We
      investigated the association of GSTM1 and GSTT1 null deletion and GSTP1 313 A/G
      polymorphisms and the risk of AD in an Iranian population. METHODS: The case
      group consisted of 280 individuals with AD and the control group included 168 age
      matched healthy individuals. The genotyping of the GSTP1 polymorphism was
      determined by PCR-RFLP and the GSTM1 and GSTT1 deletions were done by multiplex
      PCR method. RESULTS: The GSTP1 AG genotype was significantly lower (p = 0.005; OR
      = 0.57, 95% CI: 0.38-0.84) in the patients (41.1%) than the control group
      (56.5%). The GSTM1 null genotype was significantly higher (p < 0.001) in the
      patients (40.5%) than the control group (15.8%). The GSTT1 null genotype was
      significantly higher (p < 0.038) in the patients (31.2%) than the control group
      (21.5%). The patients homozygous for the GSTM1 and GSTT1 null alleles showed a
      3.5 and 1.5-fold increased risk of AD, respectively. There were interaction
      between GSTP1 AG genotype and absence of APOE e4 allele (p = 0.001), as well as
      presence of APOE epsilon4 and GSTM1 null genotype (p < 0.0001). CONCLUSION: These
      findings suggested that GSTM1 and GSTT1 null deletions may be associated with
      susceptibility to AD and people with APOE e4 and GSTM1 null deletion have a
      higher increased risk for Late-onset AD in Iranian population.

PMID- 29072552
TI  - Advances in p-Value Based Multiple Test Procedures.
AB  - In this article we review recent advances in [Formula: see text]-value-based
      multiple test procedures (MTPs). We begin with a brief review of the basic tests
      of Bonferroni and Simes. Standard stepwise MTPs derived from them using the
      closure method of Marcus et al. (1976) are discussed next. They include the well
      known MTPs of Holm (1979), Hochberg (1988) and Hommel (1988), and their
      extensions and improvements. This is followed by stepwise MTPs for a priori
      ordered hypotheses. Next we present gatekeeping MTPs (Dmitrienko and Tamhane,
      2007) for hierarchically ordered families of hypotheses with logical relations
      among them. Finally, we give a brief review of the graphical approach (Bretz et
      al., 2009) to constructing and visualizing gatekeeping and other MTPs. Simple
      numerical examples are given to illustrate the various procedures.

PMID- 29072551
TI  - Randomized controlled trial of REbeL: A peer education program to promote
      positive body image, healthy eating behavior, and empowerment in teens.
AB  - Short-term outcomes associated with participation in REbeL, a peer-led dissonance
      based eating disorder prevention program for high school students, were
      evaluated. Seventy-one students across the three high schools were enrolled in
      the study (REbeL N = 48; Control N = 23) and were assessed on measures of eating
      attitudes and behaviors, body image, weight bias, self-esteem, empowerment, and
      mood at the beginning of the school year; 37 REbeL students and 20 control
      students completed assessments at the end of the school year. Mixed effects GLM
      compared groups on outcomes at the end of the academic year. When controlling for
      baseline scores, students in both REbeL schools, compared to control school
      students, demonstrated statistically significantly lower scores at post-test on
      the EDE-Q Global score, the EDE-Q Restraint, Eating Concern, Shape Concern and
      Weight Concern subscales, and the Body Checking Questionnaire (all ps < .05).
      This study provides preliminary empirical support for the REbeL program.

PMID- 29072553
TI  - Prospective memory impairment in idiopathic REM sleep behavior disorder.
AB  - OBJECTIVE: The aim of the present study was to investigate if prospective memory
      (PM) is impaired in idiopathic rapid eye movement (REM) sleep behavior disorder
      (iRBD). RBD is a parasomnia characterized by dream enactment and by REM sleep
      without muscle atonia. iRBD is considered as the initial stage of
      neurodegeneration with pathological storage of alpha-synuclein. METHOD: Sixty
      iRBD patients with polysomnography-confirmed RBD without parkinsonism and
      dementia and 30 demographically matched normal controls (NC) were enrolled in the
      present study. Clinical assessment included Movement Disorders Society-Unified
      Parkinson's Disease Rating Scale (MDS-UPDRS), dopamine transporter single-photon
      emission computed tomography (DaT-SPECT) for imaging synapses of dopaminergic
      neurons in the striatum and a neuropsychological battery with embedded time-based
      and event-based PM measures. RESULTS: iRBD differed significantly from NC in
      event-based PM, a number of event-based failures to recall intention and total PM
      performance (all p < .001) but did not differ in time-based PM and recognition.
      PM did not contribute to impairment of instrumental activities of daily living in
      iRBD. Despite being preserved in iRBD in comparison to NC, time-based PM
      correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT.
      CONCLUSIONS: We show evidence for a differential pattern of PM impairment in iRBD
      with severe impairment of event-based and concurrent preservation of time-based
      PM. We theorize that event-based PM impairment in iRBD is caused by severe
      impairment of retention and recognition mechanisms in episodic memory whereas
      time-based PM seems to be affected by reduced striatal dopaminergic synapses.

PMID- 29072554
TI  - Functional near-infrared spectroscopy is in moderate accordance with functional
      MRI in determining lateralisation of frontal language areas.
AB  - Purpose Understanding language dominance is crucial in pre-surgical evaluation of
      patients with epilepsy and in patients having a tumour close to the language
      area. Functional magnetic resonance imaging (fMRI) studies are well established
      in evaluating language dominance. Functional near-infrared spectroscopy (fNIRS)
      is a non-invasive optical imaging modality that offers a convenient and
      affordable technique to image language-related cortical areas. This study
      investigates the agreement between results from task-based fMRI and fNIRS in
      determining language lateralisation. Methods Language laterality indices LIs were
      calculated from both fMRI and fNIRS measurements of the same individual
      volunteers by using an identical paradigm. Statistical measures of percentage
      agreement and kappa value have been calculated for testing agreement and
      reliability. Results A correlation analysis of the LI values shows a good
      correlation with r = 0.677 at p < 0.05. Statistical comparison of both fMRI and
      fNIRS methods for language lateralisation yielded a percentage agreement of 90%
      and a moderate kappa value of kappa = 0.621. Conclusion Our study suggests that
      fNIRS is in moderate accordance with fMRI in determining lateralisation of the
      frontal language areas. It implies that the optical imaging technique can provide
      additional information on functional lateralisation of frontal language areas.

PMID- 29072557
TI  - "Gay Guys are Shit-Lovers" and "Lesbians are Obsessed With Fingers": The
      (Mis)Representation of LGBTIQ People in Thai News Media.
AB  - This article presents an analysis of news reports containing information or
      opinions about lesbian, gay, bisexual, transgender, intersex, and queer (LGBTIQ)
      people taken from six Thai media outlets over a period of one year. The aim was
      to explore how LGBTIQ people are portrayed in news media narratives. LGBTIQ
      identities were found to be vastly underrepresented and, when represented, were
      often represented inaccurately, stereotypically, harmfully, or without a clear
      understanding of the diversity of sexual orientations, gender identities, and
      gender expressions. (Hetero-)sexist narratives, negative portrayals, harmful
      stereotypes, and discriminatory speech were also widely found, fueling a climate
      of stigmatization and discrimination of LGBTIQ people in Thai society. This
      article suggests that key stakeholders in Thai news media should be sensitized on
      the human rights of LGBTIQ people and on basic professional ethics in journalism.

PMID- 29072555
TI  - Streptococcus gallolyticus subsp. gallolyticus endocarditis isolate interferes
      with coagulation and activates the contact system.
AB  - Streptococcus gallolyticus subsp. gallolyticus, formerly classified as S. bovis
      biotype I, is an increasing cause of bacteremia and infective endocarditis in the
      elderly. The physiopathology of infective endocarditis is poorly understood and
      involves immune and coagulation systems. In this study, we found that S.
      gallolyticus subsp. gallolyticus activates the human contact system, which in
      turn has two consequences: cleavage of high-molecular-weight kininogen (HK)
      resulting in release of the potent pro-inflammatory peptide bradykinin, and
      initiation of the intrinsic pathway of coagulation. S. gallolyticus subsp.
      gallolyticus was found to bind and activate factors of the human contact system
      at its surface, leading to a significant prolongation of the intrinsic
      coagulation time and to the release of bradykinin. High-affinity binding of
      factor XII to the bacterial Pil1 collagen binding protein was demonstrated with a
      KD of 13 nM. Of note, Pil1 expression was exclusively found in S. gallolyticus
      subsp. gallolyticus, further supporting an essential contribution of this pilus
      in virulence.

PMID- 29072556
TI  - A Home-Based Telerehabilitation Program for Patients With Stroke.
AB  - BACKGROUND: Although rehabilitation therapy is commonly provided after stroke,
      many patients do not derive maximal benefit because of access, cost, and
      compliance. A telerehabilitation-based program may overcome these barriers. We
      designed, then evaluated a home-based telerehabilitation system in patients with
      chronic hemiparetic stroke. METHODS: Patients were 3 to 24 months poststroke with
      stable arm motor deficits. Each received 28 days of telerehabilitation using a
      system delivered to their home. Each day consisted of 1 structured hour focused
      on individualized exercises and games, stroke education, and an hour of free
      play. RESULTS: Enrollees (n = 12) had baseline Fugl-Meyer (FM) scores of 39 +/-
      12 (mean +/- SD). Compliance was excellent: participants engaged in therapy on
      329/336 (97.9%) assigned days. Arm repetitions across the 28 days averaged 24,607
      +/- 9934 per participant. Arm motor status showed significant gains (FM change
      4.8 +/- 3.8 points, P = .0015), with half of the participants exceeding the
      minimal clinically important difference. Although scores on tests of computer
      literacy declined with age ( r = -0.92; P < .0001), neither the motor gains nor
      the amount of system use varied with computer literacy. Daily stroke education
      via the telerehabilitation system was associated with a 39% increase in stroke
      prevention knowledge ( P = .0007). Depression scores obtained in person
      correlated with scores obtained via the telerehabilitation system 16 days later (
      r = 0.88; P = .0001). In-person blood pressure values closely matched those
      obtained via this system ( r = 0.99; P < .0001). CONCLUSIONS: This home-based
      system was effective in providing telerehabilitation, education, and secondary
      stroke prevention to participants. Use of a computer-based interface offers many
      opportunities to monitor and improve the health of patients after stroke.

PMID- 29072558
TI  - Co-expression and purification of the RadA recombinase with the RadB paralog from
      Haloferax volcanii yields heteromeric ring-like structures.
AB  - The study of archaeal proteins and the processes to which they contribute poses
      particular challenges due to the often extreme environments in which they
      function. DNA recombination, replication and repair proteins of the halophilic
      euryarchaeon, Haloferax volcanii (Hvo) are of particular interest as they tend to
      resemble eukaryotic counterparts in both structure and activity, and genetic
      tools are available to facilitate their analysis. In the present study, we show
      using bioinformatics approaches that the Hvo RecA-like protein RadA is
      structurally similar to other recombinases although is distinguished by a unique
      acidic insertion loop. To facilitate expression of Hvo RadA a co-expression
      approach was used, providing its lone paralog, RadB, as a binding partner. At
      present, structural and biochemical characterization of Hvo RadA is lacking.
      Here, we describe for the first time co-expression of Hvo RadA with RadB and
      purification of these proteins as a complex under in vitro conditions.
      Purification procedures were performed under high salt concentration (>1 M sodium
      chloride) to maintain the solubility of the proteins. Quantitative densitometry
      analysis of the co-expressed and co-purified RadAB complex estimated the ratio of
      RadA to RadB to be 4 : 1, which suggests that the proteins interact with a
      specific stoichiometry. Based on a combination of analyses, including size
      exclusion chromatography, Western blot and electron microscopy observations, we
      suggest that RadA multimerizes into a ring-like structure in the absence of DNA
      and nucleoside co-factor.

PMID- 29072559
TI  - Rurimicrobium arvi gen. nov., sp. nov., a member of the family Chitinophagaceae
      isolated from farmland soil.
AB  - Two strains of bacteria, designated J107-1T and J107-2, were isolated from
      farmland soil. Cells were aerobic, Gram-stain-negative, catalase- and oxidase
      positive, non-motile, non-spore-forming, coccoid rod-shaped and yellow-pigmented.
      Flexirubin-type pigments were absent. Both strains hydrolysed casein and
      tyrosine. Strains could grow at pH 9.0 and at 42  degrees C. A phylogenetic
      analysis based on its 16S rRNA gene sequence revealed that strains J107-1T and
      J107-2 formed a lineage within the phylum Bacteroidetes that was distinct from
      various members of the family Chitinophagaceae, including Ferruginibacter paludis
      HME8881T (89.71 % sequence similarity), Ferruginibacter yonginensis HME8442T,
      Niastella yeongjuensis GR20-13T (89.70 %), Chitinophaga niabensis DSM 24787T
      (89.57 %), Lacibacter cauensis CGMCC 1.7271T (89.56 %) and Taibaiella koreensis
      THG-DT86T (89.52 %). The 16S rRNA gene similarities of other members of the
      family Chitinophagaceae are less than 89.51 %. The predominant respiratory
      quinone was MK-7. The major polar lipids were phosphatidylethanolamine, an
      unidentified aminolipid and an unidentified polar lipid. Major cellular fatty
      acids were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH and iso-C17 : 0. The DNA
      G+C content of strains ranged from 47.8 to 48.0 mol%. On the basis of phenotypic,
      genotypic, chemotaxonomic and phylogenetic analysis, strains J107-1T and J107-2
      represent a novel genus in the family Chitinophagaceae, for which the name
      Rurimicrobium arvi gen. nov., sp. nov. is proposed. The type strain of
      Rurimicrobium arvi is J107-1T (=KEMB 9005-549T=KACC 19167T=JCM 31921T).

PMID- 29072560
TI  - Flavobacterium amniphilum sp. nov., isolated from a stream.
AB  - Strain KYPY10T, isolated from a water sample taken from the Funglin Stream in
      Taiwan, was characterized using a polyphasic taxonomic approach. Cells of strain
      KYPY10T were Gram-stain-negative, strictly aerobic, motile by gliding, rod-shaped
      surrounded by a thick capsule, and formed light-yellow colonies. Growth occurred
      at 20-30  degrees C (optimum, 25  degrees C), at pH 6-7 (optimum, pH 6) and with
      0-0.2 % NaCl (optimum, 0 % w/v). Phylogenetic analyses, based on 16S rRNA gene
      sequences, showed that strain KYPY10T belonged to the genus Flavobacterium and
      was most closely related to Flavobacterium brevivitae TTM-43T (98.4 % sequence
      similarity) and Flavobacterium vireti THG-SM1T (98.0 %). Strain KYPY10T contained
      iso-C15 : 0, iso-C15 : 1 G, summed feature 9 (iso-C17 : 1omega9c and/or 10-methyl
      C16 : 0), iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and iso-C16 : 0 as the predominant
      fatty acids. The major isoprenoid quinone was MK-6. The polar lipid profile
      consisted of phosphatidylethanolamine, four uncharacterized aminophospholipids,
      five uncharacterized phospholipids and one uncharacterized lipid. The major
      polyamines were homospermidine and putrescine. The genomic DNA G+C content of
      strain KYPY10T was 41.0 mol%. The DNA-DNA relatedness of strain KYPY10T with
      respect to recognized species of the genus Flavobacterium was less than 70 %. On
      the basis of the phylogenetic inference and phenotypic data, strain KYPY10T was
      recognized as a representative of a novel species within the genus
      Flavobacterium. The name Flavobacterium amniphilum sp. nov. is proposed, with
      strain KYPY10T (=BCRC 81006T=LMG 29727T=KCTC 52443T) as the type strain.

PMID- 29072561
TI  - Enterococcus wangshanyuanii sp. nov., isolated from faeces of yaks (Bos
      grunniens).
AB  - The taxonomic position of four phenotypically closely related strains isolated
      from faecal samples of yaks (Bos grunniens) collected from the Qinghai-Tibetan
      plateau, China, was determined by a polyphasic approach. The strains were non
      spore-forming, non-motile Gram-stain-positive, ovoid cocci, occurring
      predominantly in pairs and short chains or in irregular clusters. The 16S rRNA
      gene of strain MN05T was related phylogenetically to those of
      Enterococcushaemoperoxidus, Enterococcusrotai, Enterococcusquebecensis,
      Enterococcusplantarum, Enterococcuscrotali, Enterococcusmoraviensis,
      Enterococcussilesiacus, Enterococcuscaccae, Enterococcustermitis,
      Enterococcusureasiticus and Enterococcusureilyticus, all belonging to the
      Enterococcusfaecalis species group. The sequence similarities of three selected
      genes of MN05T to those of the type strains of phylogenetically related species
      were measured, with values within the range of 99.2-99.5 % (16S rRNA gene), 90.0
      97.3 % (rpoA) and 80.0-85.3 % (pheS), respectively. The genome of MN05T (3 842
      361 bp) contained 4299 genes with a DNA G+C content of 37.5 mol%. A whole-genome
      phylogenetic tree based on 808 core genes confirmed that MN05T belongs to a
      distinct lineage, well separated from all recognized species of the
      Enterococcusfaecalis species group. DNA-DNA hybridization in silico showed that
      MN05T displayed less than 70 % DNA-DNA relatedness with the other 13 species of
      the Enterococcusfaecalis species group. Moreover, their phenotypic features
      distinguished the four strains from the other species of the Enterococcusfaecalis
      species group. Based upon these data obtained from the polyphasic
      characterization performed in the present study, a novel species of the genus
      Enterococcus, Enterococcus wangshanyuanii sp. nov., is proposed, with the type
      strain MN05T (=DSM 104047T=CGMCC 1.15942T).

PMID- 29072562
TI  - Platelet to white blood cell ratio predicts 30-day postoperative infectious
      complications in patients undergoing radical nephrectomy for renal malignancy.
AB  - INTRODUCTION: We sought to examine the relationship between preoperative platelet
      to white blood cell ratio (PLT/WBC), a hematological marker of the systemic
      inflammatory response, and postoperative infectious complications following
      radical nephrectomy for localized renal cell carcinoma. METHODS: We performed a
      retrospective cohort study of patients treated with radical nephrectomy for
      localized kidney cancer between January 1, 2005 and December 31, 2014 (n=6235)
      using the American College of Surgeons (ACS) National Surgical Quality
      Improvement Program (NSQIP) database. Univariate and multivariate analyses were
      used to assess the association between PLT/WBC ratio and 30-day infectious
      complications, including surgical site infection, urinary tract infection (UTI),
      pneumonia, and sepsis. Secondarily, we examined major complications and bleeding
      requiring transfusion. RESULTS: A lower PLT/WBC ratio was associated with an
      increased risk of sepsis, pneumonia, and UTI rates (p<0.05 for all). Furthermore,
      there was a significant trend of decreasing rates of sepsis and pneumonia with
      increasing PLT/WBC ratio across quintiles (p<0.05 for all). On multivariate
      analysis, patients with the lowest PLT/WBC ratios (Quintile 1) had a two-fold
      risk of having a postoperative infectious complication compared to patients in
      the highest quintile (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.42
      2.86; p<0.0001). Patients in Quintile 5 had a higher risk of requiring blood
      transfusion than those in Quintiles 2-4 (p<0.05 for all). CONCLUSIONS: The
      PLT/WBC ratio represents a widely available and novel index to predict risk of
      infectious and bleeding complications in patients undergoing radical nephrectomy.
      External validation is required and the biological underpinning of this
      phenomenon requires further study.

PMID- 29072563
TI  - Case: Secondary polycythemia due to pazopanib in patients with metastatic renal
      cell carcinoma.

PMID- 29072564
TI  - The histopathological effects of intracavernosal mitomycin-C injection in a rat
      Peyronie's disease model.
AB  - INTRODUCTION: We aimed to evaluate whether or not mitomycin-C (MMC) has an
      antifibrotic effect on transforming growth factor-beta (TGF-beta)-induced
      Peyronie's disease (PD) in a rat model. METHODS: Eighteen 12-week-old male
      Sprague-Dawley rats were divided into three groups: Group 1=TGF-beta1 (n=7);
      Group 2=TGF-beta1+MMC (n=7); and Group 3=Sham group (0.25 ml bovine serum albumin
      injected) (n=4). All groups were sacrificed on the sixth week of the procedure
      and their penises were excised. All penis specimens were evaluated semi
      quantitatively and quantitatively with histochemical, immunohistochemistry, and
      image analysis. RESULTS: Both Group 1 and Group 2 had significantly higher
      fibrosis scores and lower elastic fibers in both outer surface of tunica
      albuginea (TA) and subsinusoidal area compared with Group 3. When compared with
      Group 1, the amount of collagen was significantly decreased in Group 2.
      Intracavernosal MMC injection (Group 2) ended up with lower elastic fibers when
      compared with Group 1. According to the quantitative analyses, when compared with
      Groups 1 and 3, lower dorsal, ventral, and trabecular thickening values were seen
      in Group 2. These parameters were only statistically significant when compared
      with Group 1, suggesting the antifibrotic effect of TGF-beta1-induced fibrosis.
      Both Groups 1 and 2 showed lower decorin staining levels in subsinusoidal areas
      of tunica albuginea (SATA) and subsinusoidal areas of trabecular wall (SATW) when
      compared with Group 3. The statistically significant difference was only detected
      between Group 1 and Group 3. CONCLUSIONS: Our study demonstrates the antifibrotic
      effects of MMC on PD. Further clinical studies are necessary to make inferences
      regarding its clinical use.

PMID- 29072565
TI  - Positive surgical margin rates during the robot-assisted laparoscopic radical
      prostatectomy learning curve of an experienced laparoscopic surgeon.
AB  - INTRODUCTION: Since its introduction, robot-assisted laparoscopic radical
      prostatectomy (RARP) has gained widespread popularity, but is associated with a
      variable learning curve. Herein, we report the positive surgical margin (PSM)
      rates during the RARP learning curve of a single surgeon with significant
      previous laparoscopic radical prostatectomy (LRP) experience. METHODS: We
      performed a prospective cohort study of the first 400 men with prostate cancer
      treated with RARP by a single surgeon (BS) with significant LRP experience. Our
      primary outcome was the impact of case timing in the learning curve on margin
      status. Our analysis was conducted by dividing the case numbers into quartiles
      (Q1-Q4) and determining if a case falling into an earlier quartile had an impact
      on margin status relative to the most recent quartile (Q4). RESULTS: The Q1 cases
      had an odds ratio for margin positivity of 1.74 compared to Q4 (p=0.1).
      Multivariate logistic regression did not demonstrate case number to be a
      significant predictor of PSM. The mean Q1 operative time was 207.4 minutes,
      decreasing to 179.2 by Q4 (p<0.0001). The mean Q1 estimated blood loss was 255.1
      ml, decreasing to 213.6 by Q4 (p=0.0064). There was no change in length of
      hospitalization within the study period. CONCLUSIONS: Even when controlling for
      copredictors, a statistically significant learning curve for PSM rate of a
      surgeon with significant previous LRP experience was not detected during the
      first 400 RARP cases. We hypothesize that previous LRP experience may reduce the
      RARP PSM learning curve.

PMID- 29072566
TI  - Does cranberry have a role in catheter-associated urinary tract infections?
AB  - INTRODUCTION: Catheter-associated urinary tract infections (CA-UTIs) are a
      prevalent and costly condition, with very few therapeutic options. We sought to
      evaluate the efficacy of an oral cranberry supplement on CA-UTIs over a six-month
      period. METHODS: Subjects with long-term indwelling catheters and recurrent
      symptomatic CA-UTIs were enrolled to take a once-daily oral cranberry supplement
      with 36 mg of the active ingredient proanthocyanidin (PACs). Primary outcome was
      reducing the number of symptomatic CA-UTIs. This was defined by >=103 (cfu)/mL of
      >=1 bacterial species in a single catheter urine specimen and signs and symptoms
      compatible with CA-UTI. Secondary outcomes included bacterial counts and
      resistance patterns to antibiotics. RESULTS: Thirty-four patients were enrolled
      in the trial; 22 patients (mean age 77.22 years, 77.27% were men) completed the
      study. Cranberry was effective in reducing the number of symptomatic CA-UTIs in
      all patients (n=22). Resistance to antibiotics was reduced by 28%. Furthermore,
      colony counts were reduced by 58.65%. No subjects had adverse events while taking
      cranberry. CONCLUSIONS: The cranberry supplement reduced the number of
      symptomatic CA-UTIs, antibiotic resistances, and major causative organisms in
      this cohort. Larger, placebo-controlled studies are needed to further define the
      role of cranberry in CA-UTIs.

PMID- 29072567
TI  - Never events and hospital-acquired conditions after kidney transplant.
AB  - INTRODUCTION: Never events (NE) and hospital-acquired conditions (HAC) after
      surgery have been designated as quality metrics in health-care by the Centres for
      Medicare and Medicaid Services (CMS). METHODS: The Nationwide Inpatient Sample
      (NIS) database 2002-2012 was used to identify patientswho underwent kidney
      transplant. Multivariate analysis using logistic regression was used to identify
      outcomes and risk factors of HAC and NE after transplantation; however, we were
      limited by using a retrospective database missing some important variables
      specified for the kidney transplant, such as some operative factors, donor
      factors, and cold and warm ischemia times. RESULTS: Among 35 058 patients who
      underwent kidney transplant, there were 11 NEs, all of which were due to retained
      foreign bodies. Among HAC after surgery, falling was the most common (44.9%),
      followed by poor glycemic control (21.7%), vascular catheter-associated infection
      (21%), and catheter-associated urinary tract infection (8%). HAC and NE after
      surgery lead to a significant increase in mortality (adjusted odds ratio [AOR]
      2.49; p=0.04), hospitalization length (13 vs. 7 days; p<0.01), and total hospital
      charges ($231 801 vs. $146 717; p<0.01). A significantly higher risk of HAC or NE
      was seen for patients who had more loss of function before surgey (AOR 3.25;
      p<0.01) and patients expected to have higher postoperative mortality before
      operation (AOR 1.62; p=0.03). CONCLUSIONS: Despite the limitations of the study,
      we found HAC and NE significantly increase mortality, hospitalization length, and
      total hospital charges of kidney transplant patients. Quality improvement
      initiatives should target HAC and NE in order to successfully reduce or prevent
      these events.

PMID- 29072568
TI  - Case: Eosinophilic cystitis presenting as a bladder mass in an 11-year-old girl.

PMID- 29072569
TI  - Comprehension and construct validity of the Visual Prostate Symptom Score (VPSS)
      by men with obstructive lower urinary tract symptoms in rural Africa.
AB  - INTRODUCTION: The Visual Prostate Symptom Score (VPSS) is an image-based
      interpretation of the International Prostate Symptom Score (IPSS) intended to
      quantify frequency, nocturia, weak stream, and quality of life (QoL) in a
      literacy-independent manner. METHODS: Ugandan men presenting with lower urinary
      tract symptons (LUTS) to a rural clinic completed VPSS and IPSS independently and
      then with assistance. They verbally interpreted VPSS images, rated question
      usefulness, and suggested improvements. Responses between word-based and image
      based measures were compared (Student's T, Fisher's exact, and Spearman's
      correlation tests). RESULTS: One hundred thirty-two scores from 33 men (mean age:
      61 years, range 28-93; education: no schooling 20%, grades 1-4 62%, 5-7 9%, 8-12
      9%). Correlation between IPSS and VPSS scores was positive (r=0.70), as was that
      between the individual irritative, obstructive, and QoL questions. Independent of
      education, the weak stream image was best-recognized. Likert scale measures
      indicated this was the most useful image, followed by daytime frequency. Nocturia
      and QoL images were rated as less clear, with explanation required before most
      understood that QoL facial expression images reflected overall LUTS impact.
      Improvements suggested included: increased image size for frequency and nocturia
      pictograms, increased black/white contrast for nocturia, and addition of an image
      to allow reporting of urgency. CONCLUSIONS: In a population with little formal
      education, there was positive correlation between IPSS and VPSS, with inherent
      recognition best for weak stream and worst for QoL images. Increased image
      clarity and an additional image for urgency will enhance the global utility of
      the VPSS for men to report symptoms of LUTS.

PMID- 29072570
TI  - A nationwide analysis of re-operation after kidney transplant.
AB  - INTRODUCTION: We aimed to report the rate and short-term outcomes of patients
      undergoing re-operation following kidney transplant in the U.S. METHODS: The
      Nationwide Inpatient Sample (NIS) database was used to examine the clinical data
      of patients undergoing kidney transplant and re-operation during same the
      hospitalization from 2002-2012. Multivariate regression analysis was performed to
      compare outcomes of patients with and without re-operation. RESULTS: We sampled a
      total of 35 058 patients who underwent kidney transplant. Of these, 770 (2.2%)
      had re-operation during the same hospitalization. Re-operation was associated
      with a significant increase in mortality (30.4% vs. 3%; adjusted odds ratio [AOR]
      4.62; p<0.01), mean total hospital charges ($249 425 vs. $145 403; p<0.01), and
      mean hospitalization length of patients (18 vs. 7 days; p<0.01). The most common
      day of re-operation was postoperative Day 1. Hemorrhagic complication (64.2%) was
      the most common reason for re-operation, followed by urinary tract complications
      (9.9%) and vascular complications (3.6%). Preoperative coagulopathy (AOR 3.35;
      p<0.01) was the strongest predictor of need for re-operation, hemorrhagic
      complications (AOR 3.08; p<0.01), and vascular complications (AOR 2.50; p<0.01).
      Also, hypertension (AOR 1.26; p<0.01) and peripheral vascular disorders (AOR
      1.25; p=0.03) had associations with hemorrhagic complications. CONCLUSIONS: Re
      operation after kidney transplant most commonly occurs on postoperative Day 1 and
      occurs in 2.2% of cases. It is associated with significantly increased mortality,
      hospitalization length, and total hospital charges. Hemorrhage is the most common
      complication. Preoperative coagulopathy is the strongest factor predicting the
      need for re-operation, vascular complications, and hemorrhagic complications.

PMID- 29072571
TI  - Efficacy of thermobalancing therapy for chronic prostatitis/chronic pelvic pain
      syndrome, confirmed by clinical study, may suggest etiology and pathophysiology
      of this disease.
AB  - INTRODUCTION: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) type-III
      is a common disorder characterized by pelvic pain and lower urinary tract
      symptoms in the absence of active infection. The aim of this clinical study is to
      evaluate the results of thermobalancing therapy (TT) and to discus the possible
      etiology and pathophysiology of CP/CPPS. METHODS: 45 patients with CP/CPPS used
      TT by applying therapeutic device, namely Dr Allen's therapeutic device (DATD),
      for six months as monotherapy. The control group comprised 45 men who did not
      receive TT. The National Institute of Health Chronic Prostatitis Symptom Index
      (NIH-CPSI) scores, prostatic volume (PV) by ultrasound measurement, and
      uroflowmetry (Qmax) were compared between both groups. RESULTS: Compared to
      controls, the treatment group showed significant improvements from baseline to
      endpoint in pain score, (p<0.001), quality of life index (QoL) (p<0.001), PV
      (p<0.001), and Qmax (p<0.001). CONCLUSIONS: The clinical study has confirmed that
      six-month TT with DATD reduces CP/CPPS symptoms dramatically. DATD uses emitted
      body heat as a source of energy to the projection of prostate for a pronged
      period of time, which removes microfocus of hypothermia in the prostate tissue
      gradually, improving blood circulation and consequently relieving the problem.
      Thus, the etiology and pathophysiology of CP/CPPS may be viewed as a chain of
      events in which initial inflammation in the prostate tissue leads to spontaneous
      capillary expansion, increasing pressure in the gland that sets up secondary,
      continuous-trigger, microfocus of hypothermia. It makes the problem chronic. TT,
      by eliminating this focus of hypothermia and pressure in the prostate gland,
      provides pelvic pain relief and improves QoL of men with CP/CPPS. The
      effectiveness of therapy allows us to recommend DATD for patients with CP/CPPS.

PMID- 29072572
TI  - Can zero-hour cortical biopsy predict early graft outcomes after living donor
      renal transplantation?
AB  - INTRODUCTION: The aim of this study was to identify relevance of subclinical
      pathological findings in the kidneys of living donors and correlate these with
      early graft renal function. METHODS: This was a prospective study on 84 living
      donor kidney transplant recipients over a period of two years. In all the donors,
      cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial,
      and tubule status. The graft function of patients with normal histology was
      compared with those of abnormal histological findings at one, three, and six
      months, and one year post-surgery. RESULTS: Most abnormal histological findings
      were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF,
      13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the
      commonly observed pathological findings in zero-hour biopsies. Only those donors
      who had histological changes of IF and ATN showed progressive deterioration of
      renal function at one month, three months, six months, and one year post
      transplantation. In donors with other histological changes, no significant effect
      on graft function was observed. CONCLUSIONS: Zero-hour cortical biopsy gave us an
      idea of the general status of the donor kidney and presence or absence of
      subclinical pathological lesions. A mild degree of subclinical and pathological
      findings on zero-hour biopsy did not affect early graft renal function in living
      donor kidney transplantation. Zero-hour cortical biopsy could also help in
      discriminating donor-derived lesions from de novo alterations in the kidney that
      could happen subsequently.

PMID- 29072574
TI  - Making connections in the brain.
AB  - Simultaneous measurements of neuronal activity and fMRI signals in the rat brain
      have shed new light on the origins of resting-state fMRI connectivity networks.

PMID- 29072573
TI  - Neoandracantha peruensis n. gen. n. sp. (Acanthocephala, Polymorphidae) described
      from cystacanths infecting the ghost crab Ocypode gaudichaudii on the Peruvian
      coast.
AB  - The cystacanths of Neoandracantha peruensis n. gen. n. sp. are described from the
      ghost crab Ocypode gaudichaudii collected from the Pacific coast of Peru. While
      it is uncommon to describe acanthocephalan taxa from immature stages, the
      presence of clear-cut distinguishing features separating the present material
      from its nearest congeneric taxa, and the absence of adults, justifies the
      erection N. peruensis. The new genus is distinguished by having three separate
      fields of trunk spines. Specimens of N. peruensis have a slender trunk with two
      anterior swellings, 3 separate fields of spines on the foretrunk swelling, and no
      genital spines on the hindtrunk. The proboscis of the new species is heavily
      armored with 21-22 longitudinal rows of 22 hooks each. Hook no. 14 is more robust
      ventrally than dorsally. Cystacanths of N. peruensis also have a long tubular
      hindtrunk and the males have diagonal testes in the midtrunk swelling. Specimens
      of the closely related Andracantha Schmidt, 1975 have anteriorly enlarged pear
      shaped Corynosoma-like trunks, only two fields of anterior trunk spines with
      occasional genital spines, and bilateral or tandem testes. Proboscides of species
      of Andracantha have considerably fewer hooks that gradually decrease in size
      posteriorly. The taxonomic component of this work is amplified by metal analysis
      of hooks and spines that shows a marked amount of magnesium (Mg) in hooks but not
      in spines. The highest level of sulfur (S) was found in the outer layer of hooks
      and anterior spines. The metal footprint of hooks and spines varies in different
      species of acanthocephalans and has an interspecific diagnostic value.

PMID- 29072577
TI  - Effect of increasing disorder on domains of the 2d Coulomb glass.
AB  - We have studied a two dimensional lattice model of Coulomb glass for a wide range
      of disorders at [Formula: see text]. The system was first annealed using Monte
      Carlo simulation. Further minimization of the total energy of the system was done
      using an algorithm developed by Baranovskii et al, followed by cluster flipping
      to obtain the pseudo-ground states. We have shown that the energy required to
      create a domain of linear size L in d dimensions is proportional to [Formula: see
      text]. Using Imry-Ma arguments given for random field Ising model, one gets
      critical dimension [Formula: see text] for Coulomb glass. The investigation of
      domains in the transition region shows a discontinuity in staggered magnetization
      which is an indication of a first-order type transition from charge-ordered phase
      to disordered phase. The structure and nature of random field fluctuations of the
      second largest domain in Coulomb glass are inconsistent with the assumptions of
      Imry and Ma, as was also reported for random field Ising model. The study of
      domains showed that in the transition region there were mostly two large domains,
      and that as disorder was increased the two large domains remained, but a large
      number of small domains also opened up. We have also studied the properties of
      the second largest domain as a function of disorder. We furthermore analysed the
      effect of disorder on the density of states, and showed a transition from hard
      gap at low disorders to a soft gap at higher disorders. At [Formula: see text],
      we have analysed the soft gap in detail, and found that the density of states
      deviates slightly ([Formula: see text]) from the linear behaviour in two
      dimensions. Analysis of local minima show that the pseudo-ground states have
      similar structure.

PMID- 29072576
TI  - Engineering multifunctional protein nanoparticles by in vitro disassembling and
      reassembling of heterologous building blocks.
AB  - The engineering of protein self-assembling at the nanoscale allows the generation
      of functional and biocompatible materials, which can be produced by easy
      biological fabrication. The combination of cationic and histidine-rich stretches
      in fusion proteins promotes oligomerization as stable protein-only regular
      nanoparticles that are composed by a moderate number of building blocks. Among
      other applications, these materials are highly appealing as tools in targeted
      drug delivery once empowered with peptidic ligands of cell surface receptors. In
      this context, we have dissected here this simple technological platform regarding
      the controlled disassembling and reassembling of the composing building blocks.
      By applying high salt and imidazole in combination, nanoparticles are
      disassembled in a process that is fully reversible upon removal of the disrupting
      agents. By taking this approach, we accomplish here the in vitro generation of
      hybrid nanoparticles formed by heterologous building blocks. This fact
      demonstrates the capability to generate multifunctional and/or multiparatopic or
      multispecific materials usable in nanomedical applications.

PMID- 29072575
TI  - A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and
      other zinc-finger proteins in meiosis.
AB  - PRDM9 binding localizes almost all meiotic recombination sites in humans and
      mice. However, most PRDM9-bound loci do not become recombination hotspots. To
      explore factors that affect binding and subsequent recombination outcomes, we
      mapped human PRDM9 binding sites in a transfected human cell line and measured
      PRDM9-induced histone modifications. These data reveal varied DNA-binding
      modalities of PRDM9. We also find that human PRDM9 frequently binds promoters,
      despite their low recombination rates, and it can activate expression of a small
      number of genes including CTCFL and VCX. Furthermore, we identify specific
      sequence motifs that predict consistent, localized meiotic recombination
      suppression around a subset of PRDM9 binding sites. These motifs strongly
      associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone
      modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's
      zinc fingers also mediate its multimerization, and we show that a pair of highly
      diverged alleles preferentially form homo-multimers.

PMID- 29072578
TI  - Anisotropic thermal and electrical transport of Weyl semimetal TaAs.
AB  - We report on anisotropic electrical, thermal as well as thermoelectric properties
      of the prototypical Weyl semimetal TaAs. Compared to the normal metallic behavior
      along a axis, TaAs is more electrically resistive along c axis and exhibits a
      semiconductor-like resistivity upturn below [Formula: see text] K. In the same
      temperature range, the thermal conductivity along c axis shows a pronounced
      maximum of 183 [Formula: see text] characteristic of a crystalline solid, three
      times higher than that of a axis. The thermoelectric power, while exhibiting
      enhanced values around room temperature, becomes diminished in a substantial
      range of temperature ([Formula: see text] K) for both axes. Together with the
      enhanced Nernst signals, this hints at a dominating ambipolar diffusion as is
      frequently seen in a compensated semimetal. An in-depth investigation of the
      anisotropic transport quantities is expected to yield deep insights into the
      propagating Weyl fermions in TaAs.

PMID- 29072580
TI  - Temperature and impurity effect on parallel field magnetoconductance of bulk
      insulating topological insulator (Bi<sub>1
      x</sub>Sb<sub>x</sub>)<sub>2</sub>Te<sub>3</sub>.
AB  - We have performed a systematic parallel field magnetotransport studies of
      (Bi<sub>1-x</sub>Sb<sub>x</sub>)<sub>2</sub>Te<sub>3</sub> to understand the
      temperature and impurity effect on interference of bulk conductance on the
      surface states of highly insulating topologically insulating compound
      Bi2Te<sub>3</sub>. The compound exhibits a weak antilocalization effect (WAL) at
      low temperature and low magnetic field. WAL weakens and weak localization (WL)
      effect is observed to be developed in the compound with the increase in the
      temperature due to the creation of topologically trivial 2D electron gas (2DEG)
      states. Strong interlayer interference and coupling of bulk carriers with surface
      states are observed at low temperature. Similar kind of temperature effect is
      observed for all the concentrations of Sb. Topologically protected surface states
      enhance with the increase in Sb contents up to x=0.3, however, further increase
      in the Sb concentration leads to decrease in the surface states. The data has
      been analysed by the generalised Altshuler and Aronov model for parallel field
      transport anticipating weak antilocalization and interlayer interference.

PMID- 29072579
TI  - Effect of the scaffold microenvironment on cell polarizability and capacitance
      determined by probabilistic computations.
AB  - In living systems, it is frequently stated that form follows function by virtue
      of evolutionary pressures on organism development, but in the study of how
      functions emerge at the cellular level, function often follows form. We study
      this chicken versus egg problem of emergent structure-property relationships in
      living systems in the context of primary human bone marrow stromal cells cultured
      in a variety of microenvironments that have been shown to cause distinct patterns
      of cell function and differentiation. Through analysis of a publicly available
      catalog of three-dimensional (3D) cell shape data, we introduce a family of
      metrics to characterize the 'form' of the cell populations that emerge from a
      variety of diverse microenvironments. In particular, measures of form are
      considered that are expected to have direct significance for cell function,
      signaling and metabolic activity: dimensionality, polarizability and capacitance.
      Dimensionality was assessed by an intrinsic measure of cell shape obtained from
      the polarizability tensor. This tensor defines ellipsoids for arbitrary cell
      shapes and the thinnest dimension of these ellipsoids, P 1, defines a reference
      minimal scale for cells cultured in a 3D microenvironment. Polarizability governs
      the electric field generated by a cell, and determines the cell's ability to
      detect electric fields. Capacitance controls the shape dependence of the rate at
      which diffusing molecules contact the surface of the cell, and this has great
      significance for inter-cellular signaling. These results invite new approaches
      for designing scaffolds which explicitly direct cell dimensionality,
      polarizability and capacitance to guide the emergence of new cell functions
      derived from the acquired form.

PMID- 29072581
TI  - High-resolution Esophageal Manometry Patterns in Children and Adolescents With
      Rumination Syndrome.
AB  - BACKGROUND: Rumination is defined by effortless regurgitation within seconds or
      minutes of ingested food. The aim of this study was to determine the high
      resolution esophageal manometry (HREM) pattern in children with rumination
      syndrome. METHODS: HREM was evaluated in 15 pediatric patients with rumination
      syndrome according to the Rome criteria and compared with 15 controls. Primary
      rumination was defined as a clinical rumination episode associated with a rise of
      gastric pressure above 30 mmHg. Secondary rumination was defined as a clinical
      rumination episode associated with a rise of gastric pressure above 30 mmHg
      during a transient lower esophageal sphincter relaxation (TLESR). RESULTS: Ninety
      two episodes of rumination were demonstrated during HREM study in 12 of the 15
      patients (80%; 1-29 episodes per patient; median intragastric pressure 49.6
      mmHg). Primary rumination occurred in 3 patients and secondary rumination in 5
      patients. One patient had primary and secondary rumination episodes. In 3
      patients, classification of rumination episodes was not possible due to
      repetitive swallowing leading to lower esophageal sphincter relaxation. In the
      control group, no episodes of rumination occurred. The sensitivity and the
      specificity of the HREM study (association of a clinical rumination episode with
      a rise in gastric pressure >30 mmHg) to confirm the diagnosis of rumination were
      80% and 100%, respectively. CONCLUSIONS: HREM allows confirming diagnosis of
      rumination syndrome and to differentiate between primary and secondary rumination
      in the presence of objective rumination episodes. Further research is needed to
      study whether HREM results may influence treatment and outcome of children with
      rumination syndrome.

PMID- 29072582
TI  - Genus-Specific Real-Time PCR and HRM Assays to Distinguish Liriope from
      Ophiopogon Samples.
AB  - Liriope and Ophiopogon species have a long history of use as traditional
      medicines across East Asia. They have also become widely used around the world
      for ornamental and landscaping purposes. The morphological similarities between
      Liriope and Ophiopogon taxa have made the taxonomy of the two genera problematic
      and caused confusion about the identification of individual specimens. Molecular
      approaches could be a useful tool for the discrimination of these two genera in
      combination with traditional methods. Seventy-five Liriope and Ophiopogon samples
      from the UK National Plant Collections of Ophiopogon and Liriope were analyzed.
      The 5' end of the DNA barcode region of the gene for the large subunit of
      ribulose-1,5-bisphosphate carboxylase/oxygenase (rbcLa) was used for the
      discrimination of the two genera. A single nucleotide polymorphism (SNP) between
      the two genera allowed the development of discriminatory tests for genus-level
      identification based on specific PCR and high-resolution melt curve (HRM) assays.
      The study highlights the advantage of incorporating DNA barcoding methods into
      plant identification protocols and provides simple assays that could be used for
      the quality assurance of commercially traded plants and herbal drugs.

PMID- 29072583
TI  - Self-Injury in Autism Spectrum Disorder and Intellectual Disability: Exploring
      the Role of Reactivity to Pain and Sensory Input.
AB  - This paper provides information about the prevalence and topography of self
      injurious behavior in children and adults with autism spectrum disorder and
      intellectual disability. Dominant models regarding the etiology of self-injury in
      this population are reviewed, with a focus on the role of reactivity to pain and
      sensory input. Neuroimaging studies are presented and suggestions are offered for
      future research.

PMID- 29072585
TI  - Biochemical Analysis of Two Single Mutants that Give Rise to a Polymorphic G6PD A
      Double Mutant.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) is a key regulatory enzyme that plays a
      crucial role in the regulation of cellular energy and redox balance. Mutations in
      the gene encoding G6PD cause the most common enzymopathy that drives hereditary
      nonspherocytic hemolytic anemia. To gain insights into the effects of mutations
      in G6PD enzyme efficiency, we have investigated the biochemical, kinetic, and
      structural changes of three clinical G6PD variants, the single mutations G6PD A+
      (Asn126AspD) and G6PD Nefza (Leu323Pro), and the double mutant G6PD A- (Asn126Asp
      + Leu323Pro). The mutants showed lower residual activity (<=50% of WT G6PD) and
      displayed important kinetic changes. Although all Class III mutants were located
      in different regions of the three-dimensional structure of the enzyme and were
      not close to the active site, these mutants had a deleterious effect over
      catalytic activity and structural stability. The results indicated that the G6PD
      Nefza mutation was mainly responsible for the functional and structural
      alterations observed in the double mutant G6PD A-. Moreover, our study suggests
      that the G6PD Nefza and G6PD A- mutations affect enzyme functions in a similar
      fashion to those reported for Class I mutations.

PMID- 29072586
TI  - Impact of 3-Aminopropyltriethoxysilane-Coated Iron Oxide Nanoparticles on
      Menaquinone-7 Production Using B. subtilis.
AB  - One of the major issues associated with industrial production of menaquinone-7
      (MK-7) is the low fermentation yield. In this study, we investigated the effect
      of iron oxide nanoparticles coated with 3-aminopropyltriethoxysilane (IONs@APTES)
      on the production of MK-7 using B. subtilis (ATCC 6633). Decoration of B.
      subtilis cells with IONs@APTES significantly enhanced both MK-7 production and
      yield. An approximately two-fold increase in MK-7 production (41 mg/L) was
      observed in the presence of 500 ug/mL IONs@APTES, as compared to MK-7 production
      using untreated bacteria (22 mg/L). This paper, therefore, illustrates the
      immense biotechnological potential of IONs@APTES in increasing MK-7 concentration
      using B. subtilis, and its future role in bioprocess engineering.

PMID- 29072584
TI  - Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature
      Aging.
AB  - Chronic high caloric intake (HCI) is a risk factor for multiple major human
      disorders, from diabetes to neurodegeneration. Mounting evidence suggests a
      significant contribution of circadian misalignment and sleep alterations to this
      phenomenon. An inverse temporal relationship between sleep, activity, food
      intake, and clock mechanisms in nocturnal and diurnal animals suggests that a
      search for effective therapeutic approaches can benefit from the use of diurnal
      animal models. Here, we show that, similar to normal aging, HCI leads to the
      reduction in daily amplitude of expression for core clock genes, a decline in
      sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable
      decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of
      that in age-matched Control, exceeds age-dependent decline observed in normal 3
      year old zebrafish. This is associated with misalignment or reduced amplitude of
      daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in
      brain tissue. Together, these data establish HCI in zebrafish as a model for
      metabolically induced premature aging of sleep, circadian functions, and adult
      neurogenesis, allowing for a high throughput approach to mechanistic studies and
      drug trials in a diurnal vertebrate.

PMID- 29072588
TI  - ESPRIT-Like Two-Dimensional DOA Estimation for Monostatic MIMO Radar with
      Electromagnetic Vector Received Sensors under the Condition of Gain and Phase
      Uncertainties and Mutual Coupling.
AB  - In this paper, we focus on the problem of two-dimensional direction of arrival
      (2D-DOA) estimation for monostatic MIMO Radar with electromagnetic vector
      received sensors (MIMO-EMVSs) under the condition of gain and phase uncertainties
      (GPU) and mutual coupling (MC). GPU would spoil the invariance property of the
      EMVSs in MIMO-EMVSs, thus the effective ESPRIT algorithm unable to be used
      directly. Then we put forward a C-SPD ESPRIT-like algorithm. It estimates the 2D
      DOA and polarization station angle (PSA) based on the instrumental sensors method
      (ISM). The C-SPD ESPRIT-like algorithm can obtain good angle estimation accuracy
      without knowing the GPU. Furthermore, it can be applied to arbitrary array
      configuration and has low complexity for avoiding the angle searching procedure.
      When MC and GPU exist together between the elements of EMVSs, in order to make
      our algorithm feasible, we derive a class of separated electromagnetic vector
      receiver and give the S-SPD ESPRIT-like algorithm. It can solve the problem of
      GPU and MC efficiently. And the array configuration can be arbitrary. The
      effectiveness of our proposed algorithms is verified by the simulation result.

PMID- 29072587
TI  - Mental Health Literacy Content for Children of Parents with a Mental Illness:
      Thematic Analysis of a Literature Review.
AB  - Millions of children have a parent with a mental illness (COPMI). These children
      are at higher risk of acquiring behavioural, developmental and emotional
      difficulties. Most children, including COPMI, have low levels of mental health
      literacy (MHL), meaning they do not have accurate, non-stigmatized information.
      There is limited knowledge about what kind of MHL content should be delivered to
      children. The aim of this exploratory study is to identify the knowledge content
      needed for general population children and COPMI to increase their MHL. A second
      aim is to explore content for emerging children's MHL scales. Researchers created
      and analyzed a literature review database. Thematic analysis yielded five main
      mental health knowledge themes for children: (1) attaining an overview of mental
      illness and recovery; (2) reducing mental health stigma; (3) building
      developmental resiliencies; (4) increasing help-seeking capacities; and (5)
      identifying risk factors for mental illness. COPMI appeared to need the same kind
      of MHL knowledge content, but with extra family-contextual content such as
      dealing with stigma experiences, managing stress, and communicating about
      parental mental illness. There is a need for MHL programs, validated scales, and
      research on what works for prevention and early intervention with COPMI children.

PMID- 29072589
TI  - The Combined Influence of Air Pollution and Home Learning Environment on Early
      Cognitive Skills in Children.
AB  - Cognitive skills are one component of school readiness that reflect a child's
      neurodevelopment and are influenced by environmental and social factors. Most
      studies assess the impact of these factors individually, without taking into
      consideration the complex interactions of multiple factors. The objective of this
      study was to examine the joint association of markers of environmental pollution
      and of social factors on early cognitive skills in an urban cohort of children.
      For this, we chose isophorone in ambient air as a marker of industrial air
      pollution. Low quality home learning environments was chosen as a marker of the
      social factors contributing to cognitive development. Using a subpopulation from
      the Early Childhood Longitudinal Study, Birth Cohort (N = 4050), isophorone
      exposure was assigned using the 2002 National Air Toxics Assessment. Home
      learning environment was assessed with a modified version of the Home Observation
      for Measurement of the Environment (HOME) Inventory, and standardized math
      assessment scores were used as a measure of early cognitive skills. Multiple
      linear regression was used to estimate the effect of both exposures on math
      scores. After adjustment for confounders, children living in areas with ambient
      isophorone in the upper quintile of exposure (>0.49 ng/m3) had math scores that
      were 1.63 points lower than their less exposed peers [95% CI: -2.91, -0.34], and
      children with lower HOME scores (at or below 9 out of 12) had math scores that
      were 1.20 points lower than children with better HOME scores [95% CI: -2.30, 
      0.10]. In adjusted models accounting for identified confounders and both
      exposures of interest, both high isophorone exposure and low HOME score remained
      independently associated with math scores [-1.48, 95% CI: -2.79, -0.18; -1.05,
      95% CI: -2.15, 0.05, respectively]. There was no statistical evidence of
      interaction between the two exposures, although children with both higher
      isophorone exposure and a low HOME score had a decrement in math scale score
      beyond the additive effect of each exposure. This was primarily observed among
      male children. These findings suggest that aspects of both the physical and
      social environments are independently associated with children's early cognitive
      skills. Future research aiming to improve children's early cognitive skills and
      subsequent school readiness should address both domains.

PMID- 29072590
TI  - Surface Acoustic Wave (SAW)-Enhanced Chemical Functionalization of Gold Films.
AB  - Surface chemical and biochemical functionalization is a fundamental process that
      is widely applied in many fields to add new functions, features, or capabilities
      to a material's surface. Here, we demonstrate that surface acoustic waves (SAWs)
      can enhance the chemical functionalization of gold films. This is shown by using
      an integrated biochip composed by a microfluidic channel coupled to a surface
      plasmon resonance (SPR) readout system and by monitoring the adhesion of biotin
      thiol on the gold SPR areas in different conditions. In the case of SAW-induced
      streaming, the functionalization efficiency is improved ~ 5 times with respect to
      the case without SAWs. The technology here proposed can be easily applied to a
      wide variety of biological systems (e.g., proteins, nucleic acids) and devices
      (e.g., sensors, devices for cell cultures).

PMID- 29072591
TI  - Frequency of Loud Snoring and Metabolic Syndrome among Korean Adults: Results
      from the Health Examinees (HEXA) Study.
AB  - Studies regarding the association between snoring and metabolic abnormalities
      have been inconsistent. We examine whether snoring frequency and obstructive
      sleep apnea markers are associated with metabolic syndrome (MetS) among Koreans
      aged 40-69 years. A total of 72,885 subjects (24,856 men, 48,029 women) from the
      Health Examinees Gem study between 2009 and 2013 were included. Snoring frequency
      was grouped into five categories (never, 1-3/month, 1-3/week, 4-5/week, 6+/week).
      Obstructive sleep apnea markers included breathing interruptions and awakenings.
      Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated
      through logistic regression. Compared with non-snorers, those who snore 6+/week
      were associated with increased odds for MetS (OR: 2.07, 95% CI: 1.91-2.25, p
      trend < 0.0001 among men; OR: 1.45, CI: 1.33-1.58, p-trend < 0.0001 among women).
      Snoring frequency is associated with MetS and its components in both men and
      women. Snoring and obstructive sleep apnea markers are important indicators of
      sleep quality, which may facilitate early detection of sleep disorders and
      further complications such as MetS.

PMID- 29072593
TI  - Synthesis, Crystal Structure, and Photoluminescent Properties of 3,3',4,4'
      Tetraethyl-5,5'-divinyl-2,2'-bipyrrole Derivatives.
AB  - Photoluminescent divinylbipyrroles were synthesized from 3,3',4,4'-tetraetyl-2,2'
      bipyrrole-5,5'-dicarboxaldehyde and activated methylene compounds via aldol
      condensation. For mechanistic clarity, molecular structures of Meldrum's acid-
      and 1,3-dimethylbarbituric acid-derived divinylbipyrroles were determined by
      single-crystal X-ray diffraction. Photoluminescent properties of the synthesized
      divinylbipyrroles in dichloromethane were found to be dependent on the presence
      of electron withdrawing groups at the vinylic terminal. The divinylbipyrroles
      derived from malononitrile, Meldrum's acid, and 1,3-dimethylbarbituric acid
      showed fluorescent peaks at 553, 576, and 602 nm respectively. Computational
      studies indicated that the alkyl substituents on the bipyrrole 3 and 3' positions
      increased energy level of the highest occupied molecular orbital (HOMO) compared
      to the unsubstituted derivatives and provided rationale for the bathochromic
      shift of the ultraviolet-visible (UV-Vis) spectra compared to the previously
      reported analogs.

PMID- 29072592
TI  - Prostate Cancer Detection with a Tactile Resonance Sensor-Measurement
      Considerations and Clinical Setup.
AB  - Tumors in the human prostate are usually stiffer compared to surrounding non
      malignant glandular tissue, and tactile resonance sensors measuring stiffness can
      be used to detect prostate cancer. To explore this further, we used a tactile
      resonance sensor system combined with a rotatable sample holder where whole
      surgically removed prostates could be attached to detect tumors on, and beneath,
      the surface ex vivo. Model studies on tissue phantoms made of silicone and
      porcine tissue were performed. Finally, two resected human prostate glands were
      studied. Embedded stiff silicone inclusions placed 4 mm under the surface could
      be detected in both the silicone and biological tissue models, with a sensor
      indentation of 0.6 mm. Areas with different amounts of prostate cancer (PCa)
      could be distinguished from normal tissue (p < 0.05), when the tumor was located
      in the anterior part, whereas small tumors located in the dorsal aspect were
      undetected. The study indicates that PCa may be detected in a whole resected
      prostate with an uneven surface and through its capsule. This is promising for
      the development of a clinically useful instrument to detect prostate cancer
      during surgery.

PMID- 29072594
TI  - Advances in Fluorescent Single-Chain Nanoparticles.
AB  - Fluorophore molecules can be monitored by fluorescence spectroscopy and
      microscopy, which are highly useful and widely used techniques in cell biology,
      biochemistry, and medicine (e.g., biomarker analysis, immunoassays, cancer
      diagnosis). Several fluorescent micro- and nanoparticle systems based on block
      copolymer micelles and cross-linked polymer networks, quantum dots, pi-conjugated
      polymers, and dendrimers have been evaluated as optical imaging systems. In this
      review, we highlight recent advances in the construction of fluorescent single
      chain nanoparticles (SCNPs), which are valuable artificial soft nano-objects with
      a small tunable size (as small as 3 nm). In particular, the main methods
      currently available to endow SCNPs with fluorescent properties are discussed in
      detail, showing illustrative examples.

PMID- 29072595
TI  - Soft Sensing of Non-Newtonian Fluid Flow in Open Venturi Channel Using an Array
      of Ultrasonic Level Sensors-AI Models and Their Validations.
AB  - In oil and gas and geothermal installations, open channels followed by sieves for
      removal of drill cuttings, are used to monitor the quality and quantity of the
      drilling fluids. Drilling fluid flow rate is difficult to measure due to the
      varying flow conditions (e.g., wavy, turbulent and irregular) and the presence of
      drilling cuttings and gas bubbles. Inclusion of a Venturi section in the open
      channel and an array of ultrasonic level sensors above it at locations in the
      vicinity of and above the Venturi constriction gives the varying levels of the
      drilling fluid in the channel. The time series of the levels from this array of
      ultrasonic level sensors are used to estimate the drilling fluid flow rate, which
      is compared with Coriolis meter measurements. Fuzzy logic, neural networks and
      support vector regression algorithms applied to the data from temporal and
      spatial ultrasonic level measurements of the drilling fluid in the open channel
      give estimates of its flow rate with sufficient reliability, repeatability and
      uncertainty, providing a novel soft sensing of an important process variable.
      Simulations, cross-validations and experimental results show that feedforward
      neural networks with the Bayesian regularization learning algorithm provide the
      best flow rate estimates. Finally, the benefits of using this soft sensing
      technique combined with Venturi constriction in open channels are discussed.

PMID- 29072597
TI  - Inferring Interaction Force from Visual Information without Using Physical Force
      Sensors.
AB  - In this paper, we present an interaction force estimation method that uses visual
      information rather than that of a force sensor. Specifically, we propose a novel
      deep learning-based method utilizing only sequential images for estimating the
      interaction force against a target object, where the shape of the object is
      changed by an external force. The force applied to the target can be estimated by
      means of the visual shape changes. However, the shape differences in the images
      are not very clear. To address this problem, we formulate a recurrent neural
      network-based deep model with fully-connected layers, which models complex
      temporal dynamics from the visual representations. Extensive evaluations show
      that the proposed learning models successfully estimate the interaction forces
      using only the corresponding sequential images, in particular in the case of
      three objects made of different materials, a sponge, a PET bottle, a human arm,
      and a tube. The forces predicted by the proposed method are very similar to those
      measured by force sensors.

PMID- 29072596
TI  - Environmental Pollution by Benzene and PM10 and Clinical Manifestations of
      Systemic Sclerosis: A Correlation Study.
AB  - Atmospheric air pollution has been associated with a range of adverse health
      effects. The environment plays a causative role in the development of Systemic
      Sclerosis (SSc). The aim of the present study is to explore the association
      between particulate (PM10) and benzene (B) exposure in Italian patients with
      systemic sclerosis and their clinical characteristics of the disease. A
      correlation study was conducted by enrolling 88 patients who suffer from SSc at
      the Fondazione Policlinico "A. Gemelli" in Rome (Italy) in the period from
      January 2013 to January 2014. The average mean concentrations of B (in 11
      monitoring sites) and PM10 (in 14 sites) were calculated using data from the
      Regional Environmental Protection Agency's monitoring stations located throughout
      the Lazio region (Italy) and then correlated with the clinical characteristics of
      the SSc patients. Of the study sample, 92.5% were female. The mean age was 55 +/-
      12.9 years old and the mean disease duration from the onset of Raynaud's
      phenomenon was 13.0 +/- 9.4 years. The Spearman's correlation showed that
      concentrations of B correlate directly with the skin score (R = 0.3; p <= 0.05)
      and inversely with Diffusing Lung Carbon Monoxide (DLCO) results (R = -0.36; p =
      0.04). This study suggests a possible role of B in the development of diffuse
      skin disease and in a worse progression of the lung manifestations of SSc.

PMID- 29072598
TI  - Toward an Asbestos Ban in the United States.
AB  - Many developed countries have banned the use of asbestos, but not the United
      States. There have, however, been multiple efforts in the US to establish strict
      exposure standards, to limit asbestos use, and to seek compensation through the
      courts for asbestos-injured workers' In consequence of these efforts, asbestos
      use has declined dramatically, despite the absence of a legally mandated ban.
      This manuscript presents a historical review of these efforts.

PMID- 29072599
TI  - Waveguide Bragg Gratings in Ormocer(r)s for Temperature Sensing.
AB  - Embedded channel waveguide Bragg gratings are fabricated in the Ormocer(r) hybrid
      polymers OrmoComp(r), OrmoCore, and OrmoClad by employing a single writing step
      technique based on phase mask technology and KrF excimer laser irradiation. All
      waveguide Bragg gratings exhibit well-defined reflection peaks within the telecom
      wavelengths range with peak heights of up to 35 dB and -3 dB-bandwidths of down
      to 95 pm. Furthermore, the dependency of the fabricated embedded channel
      waveguide Bragg gratings on changes of the temperature and relative humidity are
      investigated. Here, we found that the Bragg grating in OrmoComp(r) is
      significantly influenced by humidity variations, while the Bragg gratings in
      OrmoCore and OrmoClad exhibit linear and considerably high temperature
      sensitivities of up to -250 pm/ ? C and a linear dependency on the relative
      humidity in the range of -9 pm/%.

PMID- 29072601
TI  - Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric
      Unbinding of Monobody to H-Ras Triggered by R135K Mutation.
AB  - Ras proteins, as small GTPases, mediate cell proliferation, survival and
      differentiation. Ras mutations have been associated with a broad spectrum of
      human cancers and thus targeting Ras represents a potential way forward for
      cancer therapy. A recently reported monobody NS1 allosterically disrupts the Ras
      mediated signaling pathway, but its efficacy is reduced by R135K mutation in H
      Ras. However, the detailed mechanism is unresolved. Here, using molecular
      dynamics (MD) simulations and dynamic network analysis, we explored the molecular
      mechanism for the unbinding of NS1 to H-Ras and shed light on the underlying
      allosteric network in H-Ras. MD simulations revealed that the overall structures
      of the two complexes did not change significantly, but the H-Ras-NS1 interface
      underwent significant conformational alteration in the mutant Binding free energy
      analysis showed that NS1 binding was unfavored after R135K mutation, which
      resulted in the unfavorable binding of NS1. Furthermore, the critical residues on
      H-Ras responsible for the loss of binding of NS1 were identified. Importantly,
      the allosteric networks for these important residues were revealed, which yielded
      a novel insight into the allosteric regulatory mechanism of H-Ras.

PMID- 29072600
TI  - Protoparvovirus Cell Entry.
AB  - The Protoparvovirus (PtPV) genus of the Parvoviridae family of viruses includes
      important animal pathogens and reference molecular models for the entire family.
      Some virus members of the PtPV genus have arisen as promising tools to treat
      tumoral processes, as they exhibit marked oncotropism and oncolytic activities
      while being nonpathogenic for humans. The PtPVs invade and replicate within the
      nucleus making extensive use of the transport, transcription and replication
      machineries of the host cells. In order to reach the nucleus, PtPVs need to cross
      over several intracellular barriers and traffic through different cell
      compartments, which limit their infection efficiency. In this review we summarize
      molecular interactions, capsid structural transitions and hijacking of cellular
      processes, by which the PtPVs enter and deliver their single-stranded DNA genome
      into the host cell nucleus. Understanding mechanisms that govern the complex PtPV
      entry will be instrumental in developing approaches to boost their anticancer
      therapeutic potential and improving their safety profile.

PMID- 29072602
TI  - Isolation and Functional Characterization of an Acidic Myotoxic Phospholipase A2
      from Colombian Bothrops asper Venom.
AB  - Myotoxic phospholipases A2 (PLA2) are responsible for many clinical
      manifestations in envenomation by Bothrops snakes. A new myotoxic acidic Asp49
      PLA2 (BaCol PLA2) was isolated from Colombian Bothrops asper venom using reverse
      phase high performance liquid chromatography (RP-HPLC). BaCol PLA2 had a
      molecular mass of 14,180.69 Da (by mass spectrometry) and an isoelectric point of
      4.4. The complete amino acid sequence was obtained by cDNA cloning (GenBank
      accession No. MF319968) and revealed a mature product of 124 amino acids with Asp
      at position 49. BaCol PLA2 showed structural homology with other acidic PLA2
      isolated from Bothrops venoms, including a non-myotoxic PLA2 from Costa Rican B.
      asper. In vitro studies showed cell membrane damage without exposure of
      phosphatidylserine, an early apoptosis hallmark. BaCol PLA2 had high indirect
      hemolytic activity and moderate anticoagulant action. In mice, BaCol PLA2 caused
      marked edema and myotoxicity, the latter seen as an increase in plasma creatine
      kinase and histological damage to gastrocnemius muscle fibers that included
      vacuolization and hyalinization necrosis of the sarcoplasm.

PMID- 29072603
TI  - Atomic Sulfur: An Element for Adaptation to an Oxidative Environment.
AB  - During the period of rising oxygen concentration in the Earth's atmosphere
      (Figure 1), sulfur atoms were incorporated into proteins as redox-active cysteine
      residues [1] and antioxidant molecules such as thioredoxin, glutathione, and
      glutaredoxin appeared [...].

PMID- 29072605
TI  - Modeling of Thermal Phase Noise in a Solid Core Photonic Crystal Fiber-Optic
      Gyroscope.
AB  - A theoretical model of the thermal phase noise in a square-wave modulated solid
      core photonic crystal fiber-optic gyroscope has been established, and then
      verified by measurements. The results demonstrate a good agreement between theory
      and experiment. The contribution of the thermal phase noise to the random walk
      coefficient of the gyroscope is derived. A fiber coil with 2.8 km length is used
      in the experimental solid core photonic crystal fiber-optic gyroscope, showing a
      random walk coefficient of 9.25 * 10-5 deg/?h.

PMID- 29072604
TI  - Do Preschools Offer Healthy Beverages to Children? A Nationwide Study in Poland.
AB  - BACKGROUND: Children's beverage consumption patterns have received increased
      attention in light of the obesity epidemic in this group. In day care centers
      (DCCs), children spend up to 10 h a day, and typically consume half to three
      quarters of their daily food intake. The purpose of the study was to investigate
      what beverages are typically served to children in preschools in Poland, and to
      evaluate the practices associated with adding sugar and other sweetening agents
      to beverages. METHODS: Direct interviews with preschools staff were conducted
      with a questionnaire regarding offered beverages and adding sugar and other
      sweetening agents. The menu of 10 consecutive days and inventory reports were
      analyzed to verify information. RESULTS: A total of 720 preschools were included
      in the study. Cocoa and milk coffee substitute were served in 95% of preschools,
      followed by compote (92%), tea (84%), fruit/herbal tea (73%) and water (69%).
      Water was the only beverage available between meals (93% DCCs). 86% of preschools
      added sugar to tea/cocoa/coffee substitute drinks, and 74% to compote.
      CONCLUSIONS: In the majority of preschools, beverages which are not recommended
      were offered. Such an assortment of beverages and common practice of sweetening
      can increase the amount of added sugar in a children diet. Nutrition education
      and legal regulations concerning the assortment of beverages served in preschools
      are urgently needed.

PMID- 29072606
TI  - Tryptophan-Containing Cyclic Decapeptides with Activity against Plant Pathogenic
      Bacteria.
AB  - A library of 66 cyclic decapeptides incorporating a Trp residue was synthesized
      on solid phase and screened against the phytopathogenic bacteria Pseudomonas
      syringae pv. syringae, Xanthomonas axonopodis pv. vesicatoria, and Erwinia
      amylovora. The hemolytic activity of these peptides was also evaluated. The
      results obtained were compared with those of a collection of Phe analogues
      previously reported. The analysis of the data showed that the presence of the Trp
      improved the antibacterial activity against these three pathogens. In particular,
      40 to 46 Trp analogues displayed lower minimum inhibitory concentration (MIC)
      values than their corresponding Phe counterparts. Interestingly, 26 Trp
      containing sequences exhibited MIC of 0.8 to 3.1 MUM against X. axonopodis pv.
      vesicatoria, 21 peptides MIC of 1.6 to 6.2 MUM against P. syringae pv. syringae
      and six peptides MIC of 6.2 to 12.5 MUM against E. amylovora. Regarding the
      hemolysis, in general, Trp derivatives displayed a percentage of hemolysis
      comparable to that of their Phe analogues. Notably, 49 Trp-containing cyclic
      peptides showed a hemolysis <= 20% at 125 MUM. The peptides with the best
      biological activity profile were c(LKKKLWKKLQ) (BPC086W) and c(LKKKKWLLKQ)
      (BPC108W), which displayed MIC values ranging from 0.8 to 12.5 MUM and a
      hemolysis <= 8% at 125 MUM. Therefore, it is evident that these Trp sequences
      constitute promising candidates for the development of new agents for use in
      plant protection.

PMID- 29072608
TI  - Precise Aperture-Dependent Motion Compensation with Frequency Domain Fast Back
      Projection Algorithm.
AB  - Precise azimuth-variant motion compensation (MOCO) is an essential and difficult
      task for high-resolution synthetic aperture radar (SAR) imagery. In conventional
      post-filtering approaches, residual azimuth-variant motion errors are generally
      compensated through a set of spatial post-filters, where the coarse-focused image
      is segmented into overlapped blocks concerning the azimuth-dependent residual
      errors. However, image domain post-filtering approaches, such as precise
      topography- and aperture-dependent motion compensation algorithm (PTA), have
      difficulty of robustness in declining, when strong motion errors are involved in
      the coarse-focused image. In this case, in order to capture the complete motion
      blurring function within each image block, both the block size and the overlapped
      part need necessary extension leading to degeneration of efficiency and
      robustness inevitably. Herein, a frequency domain fast back-projection algorithm
      (FDFBPA) is introduced to deal with strong azimuth-variant motion errors. FDFBPA
      disposes of the azimuth-variant motion errors based on a precise azimuth spectrum
      expression in the azimuth wavenumber domain. First, a wavenumber domain sub
      aperture processing strategy is introduced to accelerate computation. After that,
      the azimuth wavenumber spectrum is partitioned into a set of wavenumber blocks,
      and each block is formed into a sub-aperture coarse resolution image via the back
      projection integral. Then, the sub-aperture images are straightforwardly fused
      together in azimuth wavenumber domain to obtain a full resolution image.
      Moreover, chirp-Z transform (CZT) is also introduced to implement the sub
      aperture back-projection integral, increasing the efficiency of the algorithm. By
      disusing the image domain post-filtering strategy, robustness of the proposed
      algorithm is improved. Both simulation and real-measured data experiments
      demonstrate the effectiveness and superiority of the proposal.

PMID- 29072607
TI  - Presence of Legionella spp. in Hot Water Networks of Different Italian
      Residential Buildings: A Three-Year Survey.
AB  - Although the European reports highlight an increase in community-acquired
      Legionnaires' disease cases, the risk of Legionella spp. in private houses is
      underestimated. In Pisa (Italy) we performed a three-year survey on Legionella
      presence in 121 buildings with an independent hot water production (IB); 64
      buildings with a central hot water production (CB); and 35 buildings with a solar
      thermal system for hot water production (TB). From all the 220 buildings
      Legionella spp. was researched in two hot water samples collected either at the
      recirculation point or on the first floor and on the last floor, while the
      potable water quality was analysed in three cold water samples collected at the
      inlet from the aqueduct network, at the exit from the autoclave, and at the most
      remote tap. Legionella pneumophila sg1, Legionella pneumophila sg2-16, and non
      pneumophila Legionella species were detected in 26% of the hot water networks,
      mostly in CB and TB. In these buildings we detected correlations between the
      presence of Legionella and the total chlorine concentration decrease and/or the
      increase of the temperature. Cold water resulted free from microbiological
      hazards, with the exception of Serratia liquefaciens and Enterobacter cloacae
      isolated at the exit from two different autoclaves. We observed an increase in
      total microbial counts at 22  degrees C and 37  degrees C between the samples
      collected at the most remote taps compared to the ones collected at the inlet
      from the aqueduct. The study highlights a condition of potential risk for
      susceptible categories of population and supports the need for measures of risk
      assessment and control.

PMID- 29072609
TI  - Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome.
AB  - Functional gastrointestinal disorders (FGIDs) account for at least 40% of all
      referrals to gastroenterologists. Of the 33 recognized adult FGIDs, irritable
      bowel syndrome (IBS) is the most prevalent, with a worldwide prevalence estimated
      at 12%. IBS is an important health care concern as it greatly affects patients'
      quality of life and imposes a significant economic burden to the health care
      system. Cardinal symptoms of IBS include abdominal pain and altered bowel habits.
      The absence of abdominal pain makes the diagnosis of IBS untenable. The diagnosis
      of IBS can be made by performing a careful review of the patient's symptoms,
      taking a thoughtful history (e.g., diet, medication, medical, surgical, and
      psychological history), evaluating the patient for the presence of warning signs
      (e.g., "red flags" of anemia, hematochezia, unintentional weight loss, or a
      family history of colorectal cancer or inflammatory bowel disease), performing a
      guided physical examination, and using the Rome IV criteria. The Rome criteria
      were developed by a panel of international experts in the field of functional
      gastrointestinal disorders. Although initially developed to guide researchers,
      these criteria have undergone several revisions with the intent of making them
      clinically useful and relevant. This monograph provides a brief overview on the
      development of the Rome criteria, discusses the utility of the Rome IV criteria,
      and reviews how the criteria can be applied clinically to diagnose IBS. In
      addition, a diagnostic strategy for the cost-effective diagnosis of IBS will be
      reviewed.

PMID- 29072610
TI  - Spectrum-Effect Relationships between Fingerprints of Caulophyllum robustum Maxim
      and Inhabited Pro-Inflammation Cytokine Effects.
AB  - Caulophyllum robustum Maxim (CRM) is a Chinese folk medicine with significant
      effect on treatment of rheumatoid arthritis (RA). This study was designed to
      explore the spectrum-effect relationships between high-performance liquid
      chromatography (HPLC) fingerprints and the anti-inflammatory effects of CRM.
      Seventeen common peaks were detected by fingerprint similarity evaluation
      software. Among them, 15 peaks were identified by Liquid Chromatography-Mass
      Spectrometry (LC-MS). Pharmacodynamics experiments were conducted in collagen
      induced arthritis (CIA) mice to obtain the anti-inflammatory effects of different
      batches of CRM with four pro-inflammation cytokines (TNF-alpha, IL-beta, IL-6,
      and IL-17) as indicators. These cytokines were suppressed at different levels
      according to the different batches of CRM treatment. The spectrum-effect
      relationships between chemical fingerprints and the pro-inflammation effects of
      CRM were established by multiple linear regression (MLR) and gray relational
      analysis (GRA). The spectrum-effect relationships revealed that the alkaloids (N
      methylcytisine, magnoflorine), saponins (leiyemudanoside C, leiyemudanoside D,
      leiyemudanoside G, leiyemudanoside B, cauloside H, leonticin D, cauloside G,
      cauloside D, cauloside B, cauloside C, and cauloside A), sapogenins (oleanolic
      acid), beta-sitosterols, and unknown compounds (X3, X17) together showed anti
      inflammatory efficacy. The results also showed that the correlation between
      saponins and inflammatory factors was significantly closer than that of
      alkaloids, and saponins linked with less sugar may have higher inhibition effect
      on pro-inflammatory cytokines in CIA mice. This work provided a general model of
      the combination of HPLC and anti-inflammatory effects to study the spectrum
      effect relationships of CRM, which can be used to discover the active substance
      and to control the quality of this treatment.

PMID- 29072611
TI  - A Review on Experimental Measurements for Understanding Efficiency Droop in InGaN
      Based Light-Emitting Diodes.
AB  - Efficiency droop in GaN-based light emitting diodes (LEDs) under high injection
      current density perplexes the development of high-power solid-state lighting.
      Although the relevant study has lasted for about 10 years, its mechanism is still
      not thoroughly clear, and consequently its solution is also unsatisfactory up to
      now. Some emerging applications, e.g., high-speed visible light communication,
      requiring LED working under extremely high current density, makes the influence
      of efficiency droop become more serious. This paper reviews the experimental
      measurements on LED to explain the origins of droop in recent years, especially
      some new results reported after 2013. Particularly, the carrier lifetime of LED
      is analyzed intensively and its effects on LED droop behaviors are uncovered.
      Finally, possible solutions to overcome LED droop are discussed.

PMID- 29072612
TI  - Exploring Perception of Vibrations from Rail: An Interview Study.
AB  - Rail transport is an environmentally responsible approach and traffic is expected
      to increase in the coming decades. Little is known about the implications for
      quality of life of populations living close to railways. This study explores the
      way in which vibrations from rail are perceived and described by these
      populations. The study took place in the Vastra Gotaland and Varmland regions of
      Sweden. A qualitative study approach was undertaken using semi-structured
      interviews within a framework of predetermined questions in participants' homes.
      A 26.3% response rate was achieved and 17 participants were interviewed. The
      experience of vibrations was described in tangible terms through different
      senses. Important emerging themes included habituation to and acceptance of
      vibrations, worry about property damage, worry about family members and general
      safety. Participants did not reflect on health effects, however, chronic exposure
      to vibrations through multimodal senses in individual living environments may
      reduce the possibility for restoration in the home. Lack of empowerment to reduce
      exposure to vibrations was important. This may alter individual coping
      strategies, as taking actions to avoid the stressor is not possible. The adoption
      of other strategies, such as avoidance, may negatively affect an individual's
      ability to cope with the stressor and their health.

PMID- 29072613
TI  - Thermoelectric Properties of Bi2Te3: CuI and the Effect of Its Doping with Pb
      Atoms.
AB  - In order to understand the effect of Pb-CuI co-doping on the thermoelectric
      performance of Bi2Te3, n-type Bi2Te3 co-doped with x at % CuI and 1/2x at % Pb (x
      = 0, 0.01, 0.03, 0.05, 0.07, and 0.10) were prepared via high temperature solid
      state reaction and consolidated using spark plasma sintering. Electron and
      thermal transport properties, i.e., electrical conductivity, carrier
      concentration, Hall mobility, Seebeck coefficient, and thermal conductivity, of
      CuI-Pb co-doped Bi2Te3 were measured in the temperature range from 300 K to 523
      K, and compared to corresponding x% of CuI-doped Bi2Te3 and undoped Bi2Te3. The
      addition of a small amount of Pb significantly decreased the carrier
      concentration, which could be attributed to the holes from Pb atoms, thus the CuI
      Pb co-doped samples show a lower electrical conductivity and a higher Seebeck
      coefficient when compared to CuI-doped samples with similar x values. The
      incorporation of Pb into CuI-doped Bi2Te3 rarely changed the power factor because
      of the trade-off relationship between the electrical conductivity and the Seebeck
      coefficient. The total thermal conductivity(kappatot) of co-doped samples
      (kappatot ~ 1.4 W/m?K at 300 K) is slightly lower than that of 1% CuI-doped
      Bi2Te3 (kappatot ~ 1.5 W/m?K at 300 K) and undoped Bi2Te3 (kappatot ~ 1.6 W/m?K
      at 300 K) due to the alloy scattering. The 1% CuI-Pb co-doped Bi2Te3 sample shows
      the highest ZT value of 0.96 at 370 K. All data on electrical and thermal
      transport properties suggest that the thermoelectric properties of Bi2Te3 and its
      operating temperature can be controlled by co-doping.

PMID- 29072614
TI  - A Statistical Approach to Illustrate the Challenge of Astrobiology for Public
      Outreach.
AB  - In this study, we attempt to illustrate the competition that constitutes the main
      challenge of astrobiology, namely the competition between the probability of
      extraterrestrial life and its detectability. To illustrate this fact, we propose
      a simple statistical approach based on our knowledge of the Universe and the
      Milky Way, the Solar System, and the evolution of life on Earth permitting us to
      obtain the order of magnitude of the distance between Earth and bodies inhabited
      by more or less evolved past or present life forms, and the consequences of this
      probability for the detection of associated biosignatures. We thus show that the
      probability of the existence of evolved extraterrestrial forms of life increases
      with distance from the Earth while, at the same time, the number of detectable
      biosignatures decreases due to technical and physical limitations. This approach
      allows us to easily explain to the general public why it is very improbable to
      detect a signal of extraterrestrial intelligence while it is justified to launch
      space probes dedicated to the search for microbial life in the Solar System.

PMID- 29072616
TI  - Effects of Texture and Grain Size on the Yield Strength of ZK61 Alloy Rods
      Processed by Cyclic Extrusion and Compression.
AB  - The ZK61 alloy rods with different grain sizes and crystallographic texture were
      successfully fabricated by cyclic extrusion and compression (CEC). Their room
      temperature tension & compression yield strength displayed a significant
      dependence on grain size and texture, essentially attributed to {10-12} twinning.
      The texture variations were characterized by the angle theta between the c-axis
      of the grain and the extrusion direction (ED) during the process. The contour map
      of room-temperature yield strength as a function of grain size and the angle
      theta was obtained. It showed that both the tension yield strength and the
      compression yield strength of ZK61 alloy were fully consistent with the Hall
      Patch relationship at a certain texture, but the change trends of the tension
      yield strength and the compression yield strength were completely opposite at the
      same grain size while texture altered. The friction stresses of different
      deformation modes calculated based on the texture confirmed the tension yield
      strength of the CECed ZK61 alloy rods, which was determined by both the basal
      slip and the tension twinning slip during the tension deformation at room
      temperature, while the compression yield strength was mainly determined by the
      basal slip during the compression deformation.

PMID- 29072615
TI  - The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti
      Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1
      Downregulation in Chemoresistant Lung Cancer Cells.
AB  - Multidrug resistance (MDR) is a major cause of the inefficacy and poor response
      to paclitaxel-based chemotherapy. The combination of conventional cytotoxic drugs
      has been a plausible strategy for overcoming paclitaxel resistance. Herein, we
      investigated the cytotoxic effects and underlying mechanism of LSS-11, a novel
      naphthalimide derivative-based topoisomerase inhibitor, in paclitaxel-resistant
      A549 (A549/T) lung cancer cells. LSS-11 enhanced cell death in A549/T cells by
      inducing apoptosis through increasing the DR5 protein level and PARP1 cleavage.
      Importantly, LSS-11 dose-dependently reduced STAT3 phosphorylation and
      downregulated its target genes MDR1 and MRP1, without affecting P-gp transport
      function. Chromatin coimmunoprecipitation (ChIP) assay further revealed that LSS
      11 hindered the binding of STAT3 to the MDR1 and MRP1 promoters. Additionally,
      pharmacological inhibition of p-STAT3 by sulforaphane downregulated MDR1 and
      MRP1, resulting in A549/T cell death by triggering apoptosis. Collectively, our
      data show that LSS-11 is a potent naphthalimide-based chemosensitizer that could
      enhance cell death in paclitaxel-resistant lung cancer cells through the
      DR5/PARP1 pathway and STAT3/MDR1/MRP1 STAT3 inhibition.

PMID- 29072617
TI  - Acrylated Composite Hydrogel Preparation and Adsorption Kinetics of Methylene
      Blue.
AB  - By using cyclodextrin (alpha-CD) self-assembly into a hydrogel with the triblock
      copolymer Pluronic F127, nanomicrocrystalline cellulose was introduced into a gel
      system to form a composite CNC-beta-CD/alpha-CD/Pluronic F127 hydrogel (CCH). CCH
      was modified further by grafting acrylic acid to form a novel acrylated composite
      hydrogel (ACH). The swelling degree of ACH was 156 g/g. Adsorption isotherms show
      that the adsorption process for methylene blue proximity fitted the Freundlich
      model. The adsorption kinetics showed that ACH followed a quasi-second-order
      kinetic model. Methylene blue desorption showed that ACH was a temperature- and
      pH-dependent gel. Repeated adsorption and desorption experiments were carried out
      three times, and the removal rate of methylene blue at 75 mg/L was still 70.1%.

PMID- 29072618
TI  - An Integrated Pest Management Intervention Improves Knowledge, Pest Control, and
      Practices in Family Child Care Homes.
AB  - To reduce young children's exposure to pesticides when attending family child
      care homes (FCCHs), we developed an integrated pest management (IPM) intervention
      for FCCH directors. First, we developed IPM educational materials and resources
      to provide the foundation for an IPM educational intervention for FCCHs. Next, we
      conducted and evaluated a six-month nurse child care health consultant (CCHC)-led
      education and consultation IPM intervention to increase IPM knowledge, IPM
      practices, IPM policies, and decrease the presence or evidence of pests. The
      pilot intervention study was conducted by three CCHCs in 20 FCCHs in three
      counties in California. Pre- and post-intervention measures were completed by the
      FCCH directors and observation measures were completed by the CCHCs. Results
      indicated significant increases in IPM knowledge, (t-statistic (degrees of
      freedom), (t(df) = 2.55(10), p < 0.05), increases in IPM practices (t(df) = 
      6.47(17), p < 0.05), and a 90% reduction in the prevalence of pests. There were
      no significant differences in changes in IPM practices based on director
      education, FCCH county, or IPM intervention intensity or duration. A nurse-led
      IPM education and consultation intervention can reduce exposures of young
      children attending family child care homes to harmful chemicals.

PMID- 29072619
TI  - Synthesis, Cytotoxicity and Molecular Docking Studies of the 9-Substituted 5
      Styryltetrazolo[1,5-c]quinazoline Derivatives.
AB  - In this paper, we describe the synthesis of the 5-styryltetrazolo[1,5
      c]quinazolines substituted at the 9-position with a 4-fluorophenyl ring directly
      or via a conjugated pi-spacer (C=C or C=C bond) based on the 6-bromo-4-chloro-2
      styrylquinazoline scaffold. The structures of the synthesized compounds were
      characterized based on a combination of 1H-NMR, 13C-NMR, IR and high resolution
      mass spectral data as well as microanalyses. The tetrazoloquinazolines were
      evaluated for potential in vitro cytotoxicity against the human breast
      adenocarcinoma (MCF-7) and cervical cancer (HeLa) cells. The anti-proliferative
      assays demonstrated that the 9-bromo-5-styryltetrazolo[1,5-c]quinazoline 3a and 9
      bromo-5-(4-fluorostyryl)tetrazolo[1,5-c]quinazoline 3b exhibit significant
      cytotoxicity against both cell lines. A carbon-based substituent at the 9
      position resulted in complete loss of cytotoxicity against both cell lines except
      for the 5,9-bis((E)-4-fluorostyryl)tetrazolo[1,5-c]quinazoline 4e, which was
      found to exhibit comparable cytotoxicity to that of Melphalan (IC50 = 61 MUM)
      against the MCF-7 cell line with IC50 value of 62 MUM. Molecular docking against
      tubulin (PDB:1TUB) showed that compounds 3a, 3b and 4e bind to the tubulin
      heterodimer. Binding involves hydrogen bonding for 3a and 3b and halogen
      interactions for 4e.

PMID- 29072620
TI  - Nutrient Content and Nutritional Water Productivity of Selected Grain Legumes in
      Response to Production Environment.
AB  - There is a need to incorporate nutrition into aspects of crop and water
      productivity to tackle food and nutrition insecurity (FNS). The study determined
      the nutritional water productivity (NWP) of selected major (groundnut, dry bean)
      and indigenous (bambara groundnut and cowpea) grain legumes in response to water
      regimes and environments. Field trials were conducted during 2015/16 and 2016/17
      at three sites in KwaZulu-Natal, South Africa (Ukulinga, Fountainhill and
      Umbumbulu). Yield and evapotranspiration (ET) data were collected. Grain was
      analysed for protein, fat, Ca, Fe and Zn nutrient content (NC). Yield, ET and NC
      were then used to compute NWP. Overall, the major legumes performed better than
      the indigenous grain legumes. Groundnut had the highest NWPfat. Groundnut and dry
      bean had the highest NWPprotein. For NWPFe, Zn and Ca, dry bean and cowpea were
      more productive. Yield instability caused fluctuations in NWP. Water treatments
      were not significant (p > 0.05). While there is scope to improve NWP under
      rainfed conditions, a lack of crop improvement currently limits the potential of
      indigenous grain legumes. This provides an initial insight on the nutrient
      content and NWP of a limited number of selected grain legumes in response to the
      production environment. There is a need for follow-up research to include cowpea
      data. Future studies should provide more experimental data and explore effects of
      additional factors such as management practices (fertiliser levels and plant
      density), climate and edaphic factors on nutrient content and NWP of crops.

PMID- 29072621
TI  - Synthesis and 2D-QSAR Study of Active Benzofuran-Based Vasodilators.
AB  - A new series of 2-alkyloxy-pyridine-3-carbonitrile-benzofuran hybrids (4a-x) was
      synthesized. All the new derivatives were examined via the standard technique for
      their vasodilation activity. Some of the investigated compounds exhibited a
      remarkable activity, with compounds 4w, 4e, 4r, 4s, 4f and 4g believed to be the
      most active hits in this study with IC50 values 0.223, 0.253, 0.254, 0.268, 0.267
      and 0.275 mM, respectively, compared with amiodarone hydrochloride, the reference
      standard used (IC50 = 0.300 mM). CODESSA PRO was employed to obtain a
      statistically significant 2-Dimensional Quantitative Structure Activity
      Relationship (2D-QSAR) model describing the bioactivity of the newly synthesized
      analogs (N = 24, n = 4, R2 = 0.816, R2cvOO = 0.731, R2cvMO = 0.772, F = 21.103,
      s2 = 6.191 * 10-8).

PMID- 29072622
TI  - Preparation and Application of Carboxylated Graphene Oxide Sponge in Dye Removal.
AB  - Spongy graphene is a newly developed adsorbent of high performance for water
      treatment. Proper functionalization is an efficient approach to improve the
      adsorption capacity of graphene adsorbents. In this study, we prepared graphene
      oxide (GO), functionalized it with carboxyl groups to produce carboxylated GO (GO
      COOH) dispersion, and lyophilized the GO-COOH dispersion to obtain the GO-COOH
      sponge. The adsorption isotherm, kinetics, thermodynamics, influencing factors,
      and regeneration of the adsorption of dye methylene blue (MB) on GO-COOH sponge
      were evaluated in batch experiments. The adsorption capacity of GO-COOH sponge
      was measured as 780 mg/g, which was nearly twice that of GO sponge (446 mg/g).
      The adsorption isotherm could be well described by the Freundlich model with a KF
      of 508 (L/mg)1/n. The adsorption kinetic was nicely fitted by pseudo-first-order
      model with a k1 of 0.00157.min-1. In thermodynamics analysis, the negative DeltaG
      indicated the spontaneous nature of adsorption on GO-COOH sponge. The adsorption
      process was endothermic and was driven by the increase of entropy. Higher pH
      benefited the removal of MB by GO-COOH sponge and the ionic strength had no
      meaningful effect. The regeneration was poor due to the strong electrostatic
      interaction between MB and the GO-COOH sponge. The results collectively suggested
      that carboxylation increased the adsorption performance of GO sponge.

PMID- 29072624
TI  - An Archaeosome-Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination
      Significantly Enhances Protection from Murine Melanoma.
AB  - Archaeosomes constitute archaeal lipid vesicle vaccine adjuvants that evoke a
      strong CD8+ T cell response to antigenic cargo. Therapeutic treatment of murine
      B16-ovalbumin (B16-OVA) melanoma with archaeosome-OVA eliminates small
      subcutaneous solid tumors; however, they eventually resurge despite an increased
      frequency of circulating and tumor infiltrating OVA-CD8+ T cells. Herein, a
      number of different approaches were evaluated to improve responses, including
      dose number, interval, and the combination of vaccine with checkpoint inhibitors.
      Firstly, we found that tumor protection could not be enhanced by repetitive
      and/or delayed boosting to maximize the CD8+ T cell number and/or phenotype. The
      in vivo cytotoxicity of vaccine-induced OVA-CD8+ T cells was impaired in tumor
      bearing mice. Additionally, tumor-infiltrating OVA-CD8+ T cells had an increased
      expression of programmed cell death protein-1 (PD-1) compared to other organ
      compartments, suggesting impaired function. Combination therapy of tumor-bearing
      mice with the vaccine archaeosome-OVA, and alpha-CTLA-4 administered concurrently
      as well as alpha-PD-1 and an alpha-PD-L1 antibody administered starting 9 days
      after tumor challenge given on a Q3Dx4 schedule (days 9, 12, 15 and 18),
      significantly enhanced survival. Following multi-combination therapy ~70% of mice
      had rapid tumor recession, with no detectable tumor mass after >80 days in
      comparison to a median survival of 17-22 days for untreated or experimental
      groups receiving single therapies. Overall, archaeosomes offer a powerful
      platform for delivering cancer antigens when used in combination with checkpoint
      inhibitor immunotherapies.

PMID- 29072625
TI  - Application of Circular Bubble Plume Diffusers to Restore Water Quality in a Sub
      Deep Reservoir.
AB  - Circular bubble plume diffusers have been confirmed as an effective technology
      for the restoration of the deep water system, but have never been applied in sub
      deep water system. In this study, circular bubble plume diffusers were used, for
      the first time, to restore water quality in the Aha Reservoir, a typical sub-deep
      reservoir in Southwest China. Axisymmetric intrusive gravity currents were formed
      with a horizontal radius of 250 m at the equilibrium depth and the intrusion of
      oxygen-enriched water occurred within the depth of 10-14 m, while thermal
      stratification remained intact. A total of 95% of the imported oxygen was
      dissolved, but most was consumed by organic matter and other reduced substances
      within the hypolimnion. The oxygen consumption of organic matter, NH4+ and
      remaining reduced materials, accounted for 41.4-52.5%, 25% and 13.3-24.4% of the
      total imported oxygen, respectively. Compared with the control sites, dissolved
      oxygen level in the hypolimnion increased 3-4 times, and concentrations of NH4+,
      total Fe and total Mn were reduced by 15.5%, 45.5% and 48.9%, respectively. A
      significant decrease in total phosphorus and nitrogen concentrations was observed
      in the experimental zone (0.04-0.02 mg/L and 1.9-1.7 mg/L, respectively). This
      indicates that circular bubble plumes have great potential for oxygenation of the
      hypolimnion and improving water quality in the sub-deep water system.
      Nevertheless, further efforts are needed to improve the discrete bubble model to
      elaborate the oxygen transmission dynamics and the plume formation processes in
      sub-deep water systems, incorporating oxygen consumption processes.

PMID- 29072623
TI  - How Signaling Molecules Regulate Tumor Microenvironment: Parallels to Wound
      Repair.
AB  - It is now suggested that the inhibition of biological programs that are
      associated with the tumor microenvironment may be critical to the diagnostics,
      prevention and treatment of cancer. On the other hand, a suitable wound
      microenvironment would accelerate tissue repair and prevent extensive scar
      formation. In the present review paper, we define key signaling molecules (growth
      factors, cytokines, chemokines, and galectins) involved in the formation of the
      tumor microenvironment that decrease overall survival and increase drug
      resistance in cancer suffering patients. Additional attention will also be given
      to show whether targeted modulation of these regulators promote tissue
      regeneration and wound management. Whole-genome transcriptome profiling, in vitro
      and animal experiments revealed that interleukin 6, interleukin 8, chemokine (C-X
      C motif) ligand 1, galectin-1, and selected proteins of the extracellular matrix
      (e.g., fibronectin) do have similar regulation during wound healing and tumor
      growth. Published data demonstrate remarkable similarities between the tumor and
      wound microenvironments. Therefore, tailor made manipulation of cancer stroma can
      have important therapeutic consequences. Moreover, better understanding of cancer
      cell-stroma interaction can help to improve wound healing by supporting
      granulation tissue formation and process of reepithelization of extensive and
      chronic wounds as well as prevention of hypertrophic scars and formation of
      keloids.

PMID- 29072626
TI  - Chemical Constituents from the Flower of Hosta plantaginea with Cyclooxygenases
      Inhibition and Antioxidant Activities and Their Chemotaxonomic Significance.
AB  - Two new phenolic glucosides, hostaflavanone A (1) and anti-1-phenylpropane-1,2
      diol-2-O-beta-d-glucopyranoside (2), together with six known compounds, anti-1
      phenylpropane-1,2-diol (3), phenethyl-O-beta-d-glucopyranoside (4), phenethanol
      beta-d-gentiobioside (5), phenethyl-O-rutinoside (6), (1S, 3S)-1-methyl-1,2,3,4
      tetrahydro-beta-carboline-3-carboxylic acid (7), and (1R, 3S)-1-methyl-1,2,3,4
      tetrahydro-beta-carboline-3-carboxylic acid (8), were isolated from the flower of
      Hosta plantaginea, and their structures were elucidated by nuclear magnetic
      resonance (NMR), high resolution electrospray ionization mass spectroscopy
      (HRESIMS), and circular dichroism (CD) analyses. The cyclooxygenases (COX-1 and
      COX-2) inhibition and antioxidant activities of compounds 1 and 4-6 were
      investigated, and they showed moderate cyclooxygenases inhibition activities.
      Moreover, only compound 1 exhibited moderate antioxidant activity, with an IC50
      value of 83.2 MUM, while 4-6 showed insignificant activity with IC50 values of
      282, 257, and 275 MUM, respectively. This is the first report of compounds 3 and
      5-8 from the Liliaceae family. The chemotaxonomic significance of the isolated
      compounds was also summarized.

PMID- 29072627
TI  - Anticoagulant Activity of Low-Molecular Weight Compounds from Heterometrus
      laoticus Scorpion Venom.
AB  - Scorpion venoms are complex polypeptide mixtures, the ion channel blockers and
      antimicrobial peptides being the best studied components. The coagulopathic
      properties of scorpion venoms are poorly studied and the data about substances
      exhibiting these properties are very limited. During research on the Heterometrus
      laoticus scorpion venom, we have isolated low-molecular compounds with
      anticoagulant activity. Determination of their structure has shown that one of
      them is adenosine, and two others are dipeptides LeuTrp and IleTrp. The
      anticoagulant properties of adenosine, an inhibitor of platelet aggregation, are
      well known, but its presence in scorpion venom is shown for the first time. The
      dipeptides did not influence the coagulation time in standard plasma coagulation
      tests. However, similarly to adenosine, both peptides strongly prolonged the
      bleeding time from mouse tail and in vitro clot formation in whole blood. The
      dipeptides inhibited the secondary phase in platelet aggregation induced by ADP,
      and IleTrp decreased an initial rate of platelet aggregation induced by collagen.
      This suggests that their anticoagulant effects may be realized through the
      deterioration of platelet function. The ability of short peptides from venom to
      slow down blood coagulation and their presence in scorpion venom are established
      for the first time. Further studies are needed to elucidate the precise molecular
      mechanism of dipeptide anticoagulant activity.

PMID- 29072628
TI  - Genome Modification Technologies and Their Applications in Avian Species.
AB  - The rapid development of genome modification technology has provided many great
      benefits in diverse areas of research and industry. Genome modification
      technologies have also been actively used in a variety of research areas and
      fields of industry in avian species. Transgenic technologies such as lentiviral
      systems and piggyBac transposition have been used to produce transgenic birds for
      diverse purposes. In recent years, newly developed programmable genome editing
      tools such as transcription activator-like effector nuclease (TALEN) and
      clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR
      associated protein 9 (CRISPR/Cas9) have also been successfully adopted in avian
      systems with primordial germ cell (PGC)-mediated genome modification. These
      genome modification technologies are expected to be applied to practical uses
      beyond system development itself. The technologies could be used to enhance
      economic traits in poultry such as acquiring a disease resistance or producing
      functional proteins in eggs. Furthermore, novel avian models of human diseases or
      embryonic development could also be established for research purposes. In this
      review, we discuss diverse genome modification technologies used in avian
      species, and future applications of avian biotechnology.

PMID- 29072629
TI  - A Score-Based Approach to 18F-FDG PET Images as a Tool to Describe Metabolic
      Predictors of Myocardial Doxorubicin Susceptibility.
AB  - PURPOSE: To verify the capability of 18F-fluorodeoxy-glucose positron emission
      tomography/computed tomography (FDG-PET/CT) to identify patients at higher risk
      of developing doxorubicin (DXR)-induced cardiotoxicity, using a score-based image
      approach. METHODS: 36 patients underwent FDG-PET/CT. These patients had shown
      full remission after DXR-based chemotherapy for Hodgkin's disease (DXR dose: 40
      50 mg/m2 per cycle), and were retrospectively enrolled. Inclusion criteria
      implied the presence of both pre- and post-chemotherapy clinical evaluation
      encompassing electrocardiogram (ECG) and echocardiography. Myocardial metabolism
      at pre-therapy PET was evaluated according to both standardized uptake value
      (SUV)- and score-based approaches. The capability of the score-based image
      assessment to predict the occurrence of cardiac toxicity with respect to SUV
      measurement was then evaluated. RESULTS: In contrast to the SUV-based approach,
      the five-point scale method does not linearly stratify the risk of the subsequent
      development of cardiotoxicity. However, converting the five-points scale to a
      dichotomic evaluation (low vs. high myocardial metabolism), FDG-PET/CT showed
      high diagnostic accuracy in the prediction of cardiac toxicity (specificity =
      100% and sensitivity = 83.3%). In patients showing high myocardial uptake at
      baseline, in which the score-based method is not able to definitively exclude the
      occurrence of cardiac toxicity, myocardial SUV mean quantification is able to
      further stratify the risk between low and intermediate risk classes. CONCLUSIONS:
      the score-based approach to FDG-PET/CT images is a feasible method for predicting
      DXR-induced cardiotoxicity. This method might improve the inter-reader and inter
      scanner variability, thus allowing the evaluation of FDG-PET/CT images in a
      multicentral setting.

PMID- 29072630
TI  - Liposome-Coated Iron Fumarate Metal-Organic Framework Nanoparticles for
      Combination Therapy.
AB  - One of the main problems for effective treatment of cancer is resistances, which
      often require combination therapy-for effective treatment. While there are
      already some potential drug carriers-e.g., liposomes, available for treatment-the
      effective loading and retention of the desired drug ratio can be challenging. To
      address this challenge, we propose a new type of drug carrier: liposome-coated
      metal-organic framework (MOF) nanoparticles. They combine the advantages of
      liposomes with an easy and efficient loading process. In this work, we present
      the successful synthesis of liposome-coated MOF nanoparticles via the fusion
      method. The resulting particles, once loaded, show no premature leakage and an
      efficient release. Their successful loading with both single and multiple drugs
      at the same time makes them an interesting candidate for use in combination
      therapy.

PMID- 29072631
TI  - Opportunistic Pathogens and Microbial Communities and Their Associations with
      Sediment Physical Parameters in Drinking Water Storage Tank Sediments.
AB  - The occurrence and densities of opportunistic pathogens (OPs), the microbial
      community structure, and their associations with sediment elements from eight
      water storage tanks in Ohio, West Virginia, and Texas were investigated. The
      elemental composition of sediments was measured through X-ray fluorescence (XRF)
      spectra. The occurrence and densities of OPs and amoeba hosts (i.e., Legionella
      spp. and L. pneumophila, Mycobacterium spp., P. aeruginosa, V. vermiformis,
      Acanthamoeba spp.) were determined using genus- or species-specific qPCR assays.
      Microbial community analysis was performed using next generation sequencing on
      the Illumina Miseq platform. Mycobacterium spp. were most frequently detected in
      the sediments and water samples (88% and 88%), followed by Legionella spp. (50%
      and 50%), Acanthamoeba spp. (63% and 13%), V. vermiformis (50% and 25%), and P.
      aeruginosa (0 and 50%) by qPCR method. Comamonadaceae (22.8%), Sphingomonadaceae
      (10.3%), and Oxalobacteraceae (10.1%) were the most dominant families by
      sequencing method. Microbial communities in water samples were mostly separated
      with those in sediment samples, suggesting differences of communities between two
      matrices even in the same location. There were associations of OPs with microbial
      communities. Both OPs and microbial community structures were positively
      associated with some elements (Al and K) in sediments mainly from pipe material
      corrosions. Opportunistic pathogens presented in both water and sediments, and
      the latter could act as a reservoir of microbial contamination. There appears to
      be an association between potential opportunistic pathogens and microbial
      community structures. These microbial communities may be influenced by
      constituents within storage tank sediments. The results imply that compositions
      of microbial community and elements may influence and indicate microbial water
      quality and pipeline corrosion, and that these constituents may be important for
      optimal storage tank management within a distribution system.

PMID- 29072632
TI  - Effect of Milling Time on the Microstructure, Physical and Mechanical Properties
      of Al-Al2O3 Nanocomposite Synthesized by Ball Milling and Powder Metallurgy.
AB  - The effect of milling time on the morphology, microstructure, physical and
      mechanical properties of pure Al-5 wt % Al2O3 (Al-5Al2O3) has been investigated.
      Al-5Al2O3 nanocomposites were fabricated using ball milling in a powder
      metallurgy route. The increase in the milling time resulted in the homogenous
      dispersion of 5 wt % Al2O3 nanoparticles, the reduction of particle clustering,
      and the reduction of distances between the composite particles. The significant
      grain refining during milling was revealed which showed as a reduction of
      particle size resulting from longer milling time. X-Ray diffraction (XRD)
      analysis of the nanocomposite powders also showed that designated ball milling
      contributes to the crystalline refining and accumulation of internal stress due
      to induced severe plastic deformation of the particles. It can be argued that
      these morphological and microstructural variations of nanocomposite powders
      induced by designated ball milling time was found to contribute to an improvement
      in the density, densification, micro-hardness (HV), nano-hardness (HN), and
      Young's modulus (E) of Al-5Al2O3 nanocomposites. HV, HN, and E values of
      nanocomposites were increased by ~48%, 46%, and 40%, after 12 h of milling,
      respectively.

PMID- 29072633
TI  - Endocytosis of Corn Oil-Caseinate Emulsions In Vitro: Impacts of Droplet Sizes.
AB  - The relative uptake and mechanisms of lipid-based emulsions of three different
      particle diameters by Caco-2 cells were studied. The corn oil-sodium caseinate
      emulsions showed little or no cytotoxicity even at 2 mg/mL protein concentration
      for any of the three droplet size emulsions. Confocal laser scanning microscopy
      (CLSM) of Nile red containing emulsions showed that the lipid-based emulsions
      were absorbed by Caco-2 cells. A negative correlation between the mean droplet
      size and cellular uptake was observed. There was a time-dependent and energy
      dependent uptake as shown by incubation at different times and treatment with
      sodium azide a general inhibitor of active transport. The endocytosis of lipid
      based emulsions was size-dependent. The internalization of nanoemulsion droplets
      into Caco-2 cells mainly occurred through clathrin- and caveolae/lipid raft
      related pathways, while macropinocytosis route played the most important role for
      556 nm emulsion endocytosis as shown by the use of specific pathway inhibitors.
      Permeability of the emulsion through the apical or basal routes also suggested
      that active transport may be the main route for lipid-based nanoemulsions. The
      results may assist in the design and application of lipid-based nanoemulsions in
      nutraceuticals and pharmaceuticals delivery.

PMID- 29072634
TI  - The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis
      Configuration among Deaf Koreans.
AB  - We performed targeted re-sequencing to identify the genetic etiology of early
      onset postlingual deafness and encountered a frequent TMPRSS3 allele harboring
      two variants in a cis configuration. We aimed to evaluate the pathogenicity of
      the allele. Among 88 cochlear implantees with autosomal recessive non-syndromic
      hearing loss, subjects with GJB2 and SLC26A4 mutations were excluded. Thirty-one
      probands manifesting early-onset postlingual deafness were sorted. Through
      targeted re-sequencing, we detected two families with a TMPRSS3 mutant allele
      containing p.V116M and p.V291L in a cis configuration, p.[p.V116M; p.V291L]. A
      minor allele frequency was calculated and proteolytic activity was measured. A
      p.[p.V116M; p.V291L] allele demonstrated a significantly higher frequency
      compared to normal controls and merited attention due to its high frequency
      (4.84%, 3/62). The first family showed a novel deleterious splice site variant
      c.783-1G>A-in a trans allele, while the other showed homozygosity. The
      progression to deafness was noted within the first decade, suggesting DFNB10. The
      proteolytic activity was significantly reduced, confirming the severe
      pathogenicity. This frequent mutant allele significantly contributes to early
      onset postlingual deafness in Koreans. For clinical implication and proper
      auditory rehabilitation, it is important to pay attention to this allele with a
      severe pathogenic potential.

PMID- 29072636
TI  - [Scientific and clinical activity of Central Research Institute of Dentistry and
      Maxillofacial Surgery].

PMID- 29072635
TI  - A Systematic Review of Neuroprotective Strategies during Hypovolemia and
      Hemorrhagic Shock.
AB  - Severe trauma constitutes a major cause of death and disability, especially in
      younger patients. The cerebral autoregulatory capacity only protects the brain to
      a certain extent in states of hypovolemia; thereafter, neurological deficits and
      apoptosis occurs. We therefore set out to investigate neuroprotective strategies
      during haemorrhagic shock. This review was performed in accordance to the PRISMA
      (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
      Before the start of the search, a review protocol was entered into the PROSPERO
      database. A systematic literature search of Pubmed, Web of Science and CENTRAL
      was performed in August 2017. Results were screened and evaluated by two
      researchers based on a previously prepared inclusion protocol. Risk of bias was
      determined by use of SYRCLE's risk of bias tool. The retrieved results were
      qualitatively analysed. Of 9093 results, 119 were assessed in full-text form, 16
      of them ultimately adhered to the inclusion criteria and were qualitatively
      analyzed. We identified three subsets of results: (1) hypothermia; (2) fluid
      therapy and/or vasopressors; and (3) other neuroprotective strategies (piracetam,
      NHE1-inhibition, aprotinin, human mesenchymal stem cells, remote ischemic
      preconditioning and sevoflurane). Overall, risk of bias according to SYRCLE's
      tool was medium; generally, animal experimental models require more rigorous
      adherence to the reporting of bias-free study design (randomization, etc.). While
      the individual study results are promising, the retrieved neuroprotective
      strategies have to be evaluated within the current scientific context-by doing
      so, it becomes clear that specific promising neuroprotective strategies during
      states of haemorrhagic shock remain sparse. This important topic therefore
      requires more in-depth research.

PMID- 29072637
TI  - [Morphology of epithelial-mesenchymal transformation in neoplasias of oral
      mucosa].
AB  - The aim of the study was to assess correlation of E-cadherin and N-cadherin
      expression with proliferative activity and neoplasia grade in oral mucosa. Oral
      biopsies of 48 patients were studied with focal hyperplasia, squamous
      intraepithelial neoplasia and oral squamous cell carcinoma. Tissue antigens were
      determined using a mouse monoclonal antibody to Ki-67 and E-cadherin and rabbit
      polyclonal antibodies to N-cadherin. The study revealed correlation between the
      proliferative activity of epithelial cells and N-cadherin synthesis associated
      with decline of E-cadherin expression. Intercellular junction proteins E- and N
      cadherins may be used for early diagnosis of malignant transformation of oral
      squamous epithelium.

PMID- 29072638
TI  - [Regulatory framework of the new wage payment system in dentistry].
AB  - The paper presents the analysis of regulatory frameworks for wage payment system
      in federal, state and municipal dental clinics. The new wage payment system
      provided significant freedom for employers in payments size determination by
      regulation of basic, stimulating and compensative salary payoffs. The study
      highlights the need for scientific studies on dental care quality assessment
      criteria for wage payment system.

PMID- 29072639
TI  - [Guidelines for dental care in departmental sanatoriums for workers with
      hazardous working conditions].
AB  - The aim of the study were protocols of dental care in departmental sanatoriums
      for workers with hazardous working conditions (HWC). Provided dental care and
      staff features were analyzed in 10 sanatoriums basing on their annual 2016
      reports. In Central Clinical Sanatorium 'Malakhovka' dental care need was
      assessed in 402 males (mean age 39.2+/-1.2 years) with HWC. The study results
      were used for guidelines of departmental 'Dental care in resort rehabilitation of
      workers with hazardous working conditions'.

PMID- 29072640
TI  - [Quality of oral surgery and patients' satisfaction in state and municipal
      clinics].
AB  - The aim of the multicenter study was to assess quality of oral surgical
      procedures and patients' satisfaction in state and municipal clinics in different
      regions of Russian Federation. A questionnaire survey was conducted in 3 regions
      of Russian Federation: European (Moscow, Tula, Tambov, Kaluga, Volgograd), North
      (Saint-Petersburg, Novgorod, Tver) and South (Armavir, Derbent, Kaspiysk,
      Kislovodsk, Makhachkala, Pyatigorsk, Rostov, Sochi, Stavropol). Sixty-six males
      and 34 females undergoing surgical dental treatment in public and municipal
      dental clinics (total number - 100 patients) at the age of 20 to 70 years (an
      average age was 36,3 and 39.5, respectively) were included in the study.
      Comparative analysis of patients' satisfaction rates in relation with expert
      evaluated quality of oral surgery is presented.

PMID- 29072641
TI  - [Manifestation of Crohn's disease in the oral cavity: clinical case].
AB  - The article contains the review of possible oral manifestations of Crohn's
      disease and clinical case presentation of purulent alveolitis resistant to
      conventional local treatment, geographical glossitis and xerostomia in 42 y.o.
      female with the history of periodical digestive disorders, diagnosed with Crohn's
      disease. The diagnosis was based on abovementioned oral manifestations.

PMID- 29072642
TI  - [Complex treatment of recurrent herpetic stomatitis with dysbiosis].
AB  - Research objective was to study the effectiveness of complex treatment of
      recurrent herpetic stomatitis with dysbiosis. The study included 147 patients
      aged from 18 to 45 years with recurrent herpetic stomatitis (RGS) and disbyosis
      divided in 3 groups. Group 1 received conventional antiviral and symptomatic
      treatment of RGS, in group 2 complex immunoglobulins (IgA (15-25%), IgM (15-25%)
      and Ig (50-70%)) were added to conventional therapy, group 3 received
      immunoglobulins only. Clinical and immunological efficiency was estimated by
      values of oral local immunity (SlgA, lysozyme), humoral immunity (IgE and IgG)
      and cellular immunity (RBTL with FGA, defined T-lymphocytes). Significant
      (p<0.05) increase of lisozyme and SlgA, RBTL with FGA, number of T-lymphocytes
      and IgG concentration was observed in group 2. The obtained data allow improving
      quality of treatment of recurrent herpetic stomatitis with related dysbiosis.

PMID- 29072643
TI  - [Correlation of functional state of dental system and emotional stress in young
      adults].
AB  - The aim of the study was to evaluate correlation of dental system functional
      status and emotional stress level in young adults. The study involved 164
      patients aged 20-25 years. TMJ dysfunction was diagnosed according to M. Ahlers
      and H. Jakstat criteria (2000). All patients underwent electromyography (EMG) of
      mastication muscles at rest and by functional test. Emotional stress and anxiety
      were assessed by Holmes and Rahe stress scale, Jakhin-Mendeleevich clinical
      questionnaire and State-Trait Anxiety Inventory. The study revealed correlation
      between EMG activity of masticatory muscles and emotional stress level
      highlighting the importance of stress assessment in TMJ dysfunction planning.

PMID- 29072644
TI  - [Gender related salivation features].
AB  - The aim of the study was to assess gender related salivation features. One
      hundred and seventy-five patients were enrolled in the study (115 females and 60
      males aged from 18 to 75 years). The study results showed xerostomia to be more
      common in females and it's subjective symptoms are more prominent partly because
      of gender-related psychological reasons. Xylitol-based paste and spray were
      successfully used for symptoms relief.

PMID- 29072645
TI  - [Endoscopic surgery in the treatment of patients with extensive odontogenic
      cysts].
AB  - The aim of the study was the assessment of effectiveness of endoscopic techniques
      in the treatment of extensive odontogenic cysts. Endosurgery for diagnostic and
      therapeutic purposes was used in 67 patients with odontogenic cysts of the jaws:
      23 follicular cysts, 19 radicular cysts, 6 residual cysts, and 19 keratokists.
      The results prove that the developed methods of endovideosurgery of odontogenic
      cysts have low invasiveness, provide an optimal healing of bone tissue and reduce
      postoperative complications.

PMID- 29072646
TI  - [Clinical and radiological features of inflammatory lesions in the lower molars
      area].
AB  - The study objective was to analyze clinical manifestations by various forms of
      inflammatory destructive lesions in lower molars area. The study included 54
      patients aged 20 to 66 years with odontogenic alveolar bone defects in lower
      molars area. Typical clinical and radiological signs are described for each type
      of destructive lesions. Sinus tract located more coronal and 'areolar' bone
      resorption may indicate root perforation. Clinical and radiological features may
      help in choosing optimal surgical tactic.

PMID- 29072647
TI  - [Comparative biomechanical study of surgically assisted rapid palatal expansion
      with tooth-borne and bone-borne expanders].
AB  - The study objective was to compare the biomechanics of surgically assisted rapid
      palatal expansion (SARPE) with tooth-borne and bone-borne expanders. Materials
      include a sample of 54 cone-beam CT of 27 patients who underwent SARPE (bone
      borne, n=21; tooth-borne, n=6) before treatment and at expander removal.
      Expansion efficacy was estimated by interapecal and intercoronal distances
      between maxillary canines, premolars and first molars as well as Coronal-Apical
      Index (CAI = coronal expansion (mm)/apical expansion (mm)). CAI varied between
      1.5 and 2.0 in the group of patients with bone-borne appliances, and from 2.3 to
      2.6 in the tooth-borne appliances group. The maximal amount of vestibular coronal
      declination was revealed in premolars by the use of tooth-borne appliances. Bone
      borne appliances allowed lateralization of maxilla and the most prominent effect
      of tooth shift in a vestibular direction, which may be seen as the most important
      factors in a relapse prevention.

PMID- 29072648
TI  - [Mental health of elderly and old people when using a complete dry dental
      prosthesis: myth or reality?]
AB  - The study studied the ratio of 17 adults with complete loss of teeth and using
      complete removable acrylic dentures, to the disease, taking into account the
      degree of stability of dentures during chewing. To determine the type of
      patient's attitude toward the disease, a clinical test method was used to
      determine the type of attitude towards the disease, in which the clinical
      psychological typology of patients' attitude to 'illness' was realized, which
      provides the possibility of determining one of the twelve types of response. It
      was found that when using complete removable dentures, regardless of age and sex,
      the types of attitude towards the disease were more often noted, with a marked
      disadaptive behavior with a predominantly intrapsychic orientation of the
      response to the disease, which was manifested by characteristic reactions such as
      irritable weakness, anxious, depressed, oppressed state. The use of the cream to
      fix the removable dental prostheses Corega allowed to improve the stability of
      complete removable dentures, to eliminate the pronounced phenomena of mental
      disadaptation, and to create realistic treatment settings for patients, to help
      restore social ties.

PMID- 29072649
TI  - [Algorithm of orthodontic treatment of cleft lip and palate patients before and
      after autogenous bone grafting].
AB  - The aim of the study was to elaborate the algorithm of orthodontic treatment of
      cleft lip and palate (CLP) patients. One hundred and twenty-six CLP patients
      after CLP plasty preparing for alveolar ridge reconstruction were divided into 3
      groups according to their age: 47 (37%) patients aged 6 to 11 years; 50 (40%)
      aged 12 to 17 years; 29 (23%) patients aged 18-27. Eighty-four (66.7%) patients
      had unilateral CLP and 42 (33.3%) had bilateral CLP. Complex examination revealed
      typical dental and maxillofacial features for each group. Clinical and diagnostic
      imaging data allowed formulating rationale for complex treatment approach and
      algorithm of treatment option choice according to patients age at the time of
      alveolar ridge reconstruction.

PMID- 29072650
TI  - [Caries prevention with fluoridated and iodinated salt in school-aged children
      living in areas with fluoride and iodine deficiency].
AB  - The aim of the study was to evaluate the efficacy of dental caries prevention
      program with 3 years follow-up in children living in areas with fluoride and
      iodine deficiency. The study involved 625 school-aged children aged 6, 12 and 15
      years receiving endogenous prevention with fluoridated and iodinated salt (300+/
      50 mgF/kg and 40+/-10 mgI/kg). Enamel and dentine concentrations of CA, P, F and
      I were measured in 98 intact deciduous teeth by X-ray microanalysis before and
      after prevention program. Enamel and dentin microhardness was assessed in the
      same 98 teeth by Vickers Hardness Test. Obtained reduction of DMFT growth,
      positive changes of mineral composition and dental hard tissues microhardness
      prove high clinical efficacy of applied prevention program.

PMID- 29072651
TI  - [Imaging diagnostic methods for identification of sentinel lymph nodes in
      patients with early squamous cell carcinoma of the oral cavity mucosa: a
      literature review].
AB  - The paper describes properties of clinical visualization approaches which are
      applied for detection of sentinel lymph nodes in patients suffering from oral
      cavity squamous cell cancer. Diagnostic efficiency results and technological
      features of different imaging techniques are discussed.

PMID- 29072652
TI  - [The modern aspects of the treatment of the patients presenting with bilateral
      laryngeal paralysis depending on the duration of the disease].
AB  - AIM: the objective of the present study was to increase the functional
      effectiveness of the combined treatment of the patients presenting with bilateral
      laryngeal paralysis on the basis of the development of a medical diagnostic
      algorithm taking into consideration the peculiar etiological and pathogenic
      features of the clinical course of the disease. The study included 102 patients
      suffering from bilateral paralysis of the larynx. The duration of the disease
      varied from 2 months to 26 years. All the patients underwent the preoperative
      preparation followed by laryngoplasty surgery for unilateral
      myoaritenoidchordectomy. The patients who had no tracheostoma at admittance were
      treated by simultaneous tracheostomy and laryngoplasty. The study made it
      possible to identify the factors that exerted the adverse influence on the
      outcome of the operation, such as prolonged cannulation, a protracted course of
      the disease (for more than 1 year), longer periods of recovery of the external
      respiration function characteristics, increased duration of the hospitalization
      and rehabilitation periods that lasted over more than one year, and a rise in the
      number of the patients carrying the cannulas. Taken together, the proposed
      algorithm for the examination and treatment of the patients presenting with
      bilateral laryngeal paralysis, the early diagnostics of the disease, and the
      differential approach to its treatment made it possible to reduce the frequency
      of the immediate and long-term postoperative complication and decrease the
      duration of hospitalization and rehabilitation of the patients.

PMID- 29072653
TI  - [Peculiarities of the early diagnostics of malignant nasopharyngal neoplasms].
AB  - The authors consider the risk factors and the specific clinical symptoms of the
      malignant nasopharyngal neoplasms as well as the methods for instrumental,
      laboratory, and pathomorphological diagnostics of this pathology. The full scale
      implementation of the recommendations for the timely detection of the tumours
      using the aforementioned diagnostic procedures and tests makes it possible to
      reduce to a minimum the interval between the establishment of the diagnosis and
      the onset of the relevant treatment at the early stages of the disease and
      thereby to ensure the improvement of its long-term outcomes.

PMID- 29072654
TI  - [The specific features of the past medical history and etiology of pharyngeal
      abscess in the children].
AB  - The present study was undertaken for the purpose of elucidating the specific
      features of the past medical history and the etiological factors responsible for
      the development of tonsillogenic pharyngeal abscesses in the children. We
      performed the retrospective analysis of the medical histories of 291 children
      presenting with this condition who had been admitted for the treatment to the ENT
      Department of the Morozovskzya City Children's Clinical Hospital during the
      period from January till December 2015. The study has demonstrated the following
      most common shortcomings of the outpatient treatment of the patients suffering
      from chronic tonsillitis at the stage preceding formation of paratonsillar
      abscess: inadequate antibacterial therapy of acute chronic tonsillitis or its
      exacerbation and limited indications for tonsillectomy at the level of the
      outpatient treatment. The leading role in the etiology of tonsillogenic
      pharyngeal abscesses in the children is played by beta-hemolytic Streptococcus of
      group A. It is concluded that the medical history suggesting past paratonsillar
      abscess is the absolute indication for the subsequent tonsillectomy in the
      children of any age.

PMID- 29072655
TI  - [The specific features of the clinical course of acute suppurative otitis media
      of viral and mixed viral-bacterial etiology in the children of the preschool
      age].
AB  - The objective of the present study was to elucidate the spectrum of the
      pathogenic agents responsible for the development of acute suppurative otitis
      media in the children of the preschool age and to reveal the specific clinical
      features of this disease depending on its etiological factors. The study involved
      138 patients (186 ears) of either sex at the age from 1 year to 84 months who
      presented with acute suppurative otitis media. The following methods were
      employed for the purpose of the study: analysis of the patients' complaints and
      the past medical histories, examination of the ENT organs, microbiological
      (bacteriological and virological) studies of secretion from the tympanic cavity,
      diagnostic endoscopy of the nasal cavity and nasopharynx, laboratory
      investigations. The study allowed to reveal the characteristic clinical
      manifestations of the pathology of interest depending on its etiology.

PMID- 29072656
TI  - [The endoscopic anatomy of the middle ear (a dissection study)].
AB  - The objective of the present work was to study the specific endoscopic anatomical
      features of the middle ear using the dissected temporal bones with the intact
      tympanic membrane. The 18 cm long endoscopes 4 mm in diameter with a visual angle
      from 0 to 45 degrees in the combination with some other microinstruments, such as
      ear pincers, needles, curettes, elevators, and suction tubes, were used during
      the examination. It was shown that endomeato-transtympanic endosopy provides a
      panoramic view of almost all structures of the middle ear. After the resection of
      the posterior bone edge of 'annulus tympanicus', the use of the 45o endoscope
      ensured the panoramic view not only of certain structures of the middle ear (e.g.
      the tympanic chord, the stapedius muscle tendon, the entire pyramidal process)
      but also of the structures of the retrotympanic and anterior epitympanic spaces.

PMID- 29072657
TI  - [The influence of biological compatibility of the cyanoacrylate glue on
      regeneration of the cartilaginous tissue].
AB  - The objective of the present study was to evaluate the possibility of the
      application of the cyanoacrylate-based glue for the strengthening of the
      reconstructed elements of the middle ear and its influence on the regeneration of
      the cartilaginous tissue. We used the cartilaginous tissue from the auricles of
      the male California rabbits as a model. The cartilage was destroyed in a standard
      press. Half of the cartilage thus fragmented was implanted into the left auricle.
      The remaining part was mixed up with the cyanoacrylate glue and implanted into
      the right auricle of the same animal. The implanted material was used for the
      morphological study on day 10, within 1 and 2 months after the beginning of the
      experiment. The results of the study confirm the absence of the toxic action of
      the biologically compatible cyanoacrylate-based glue on the regeneration of the
      cartilaginous and connective tissues which suggests the possibility of its
      application for the surgical treatment of the diseases of the middle ear.

PMID- 29072658
TI  - [The evaluation of the quality of life in the patients presenting with various
      forms of chronic otitis media].
AB  - Chronic otitis media (COM) is a widespread pathological condition that affects up
      to 2% of the general population. Certain forms of this disease markedly
      deteriorate the quality of life of the patients which makes them overestimate the
      severity of harm to their health status and can be a cause of inflated
      expectations as regards the results of the planned surgical treatment. The
      linking element between the patient's expectations and the outcomes of the
      surgical intervention may be the recently developed questionnaires for the
      evaluation of the health-related quality of life (HRQoL). One of them, the COMQ
      12 questionnaire, was devised to estimate the subjective reports by the patients
      concerning the deterioration of their quality of life attributable to chronic
      otitis media. The objective of the present study was to characterize the value of
      the 5-point Russian-language version of COMQ-12 for the evaluation of each of its
      12 items concerning various aspects of health based on the personal opinions of
      the patients suffering from chronic otitis media The study included 108 patients
      49 of whom were men and 59 women (45% and 55% respectively) at the age varying
      from 16 to 84 years. The COMQ-12 scores, according to the reports of individual
      patients, ranged from 4 to 43 of the 60 ones possible. The average score was 19.4
      (SD=8.3). The overall median COMQ-12 score was 20, and the mode scored 14. The
      Cronbach-alpha index was equal to 0.860. The Russian-language version of the COMQ
      12 questionnaire provides a reliable tool for the estimation of the quality of
      life in the patients presenting with various forms of chronic otitis media.

PMID- 29072659
TI  - [Characteristic of the microbiocenosis of the nasal mucous membrane in the
      patients presenting with acute bacterial rhinosinusitis].
AB  - The objective of the present work was to study the specific features of the
      microbiocenosis of the nasal mucous membrane in the patients presenting with
      acute bacterial rhinosinusitis (ABRS). We examined 86 patients with this
      condition at the age varying from 18 to 64 years. The control group consisted of
      practically healthy blood donors (n=156) registered at the Krasnoyarsk Regional
      Blood Centre #1; they were matched to the patients of the main study group in
      terms of the age and sex. In order to investigated bacterial flora of nasal
      mucosa from the standpoint of its role in the exacerbation of the disease, the
      microorganisms were cultured on the differential-diagnostic media. Their
      individual species were identified with the use of the conventional
      microbiological methods. They demonstrated the disturbances of the
      microbiocenosis of the nasal mucous membrane of the ABRS patients with the
      simultaneous increase of the total abundance of microorganisms regarded as
      potentially pathogenic ones. The study of pathogenic and persistent properties of
      the Staphylococcus strains isolated from the nasal mucosa of the patients
      suffering from acute bacterial rhinosinusitis, revealed the presence of
      practically all species supposed to be etiopathogenic agents able to produce the
      enzymes responsible for pathogenicity and persistence of the microorganisms. The
      results of the present study were interpreted as giving evidence of the
      disturbances of the microbiocenosis of the nasal mucosa resulting from the
      impairment of local immunity associated with trophic disorders in the mucous
      membrane of the nasal passages.

PMID- 29072660
TI  - [The role of a leukotriene receptor antagonist in the restoration of the nasal
      breathing in the patients presenting with polypous rhinosinusitis].
AB  - The present study was designed to investigate the clinical. laboratory, and
      morphological characteristics of the nasal obstruction process. It included 87
      patients presenting with polypous rhinosinusitis. The dynamics of the serum
      leukotriene C4 (LTC4) level in the patients and the morphological changes in
      their polypous tissue suggested the existence of the pronounced exudative phase
      of allergic inflammation and provided a basis for the use of the leukotriene
      receptor antagonist in the form of the sodium montelucast tablets for the
      treatment of nasal obstruction.

PMID- 29072661
TI  - [The application of the computer technologies for the mathematical simulation of
      the ethmoidal labyrinth].
AB  - The objective of the present work was to study the relationship between the
      dimensions of the ethmoidal labyrinth and the skull in the subjects differing in
      the nose shape by means of the factorial and correlation analysis with the
      application of the modern computer-assisted methods for the three-dimensional
      reconstruction of the skull. We developed an original method for computed
      craniometry with the use the original program that made it possible to determine
      the standard intravital craniometrics characteristics of the human skull with a
      high degree of accuracy based on the results of analysis of 200 computed
      tomograms of the head. It was shown that the length of the inferior turbinated
      bones and the posterior edge of the orbital plate is of special relevance for
      practically all parameters of the ethmoidal labyrinth. Also, the width of the
      choanae positively relates to the height of the ethmoidal labyrinth.

PMID- 29072662
TI  - [The potential of physiotherapy after rhinoplasty].
AB  - This article presents the results of the evaluation of the effectiveness of
      physiotherapy during the postoperative period following rhinoplastic surgery
      based on the analysis of the dynamics of the clinical symptoms in 374 patients
      divided into two groups. The main group was comprised of 286 (86.5%) patients who
      had undergone the comprehensive postoperative rehabilitation with the use of the
      chosen physiotherapeutic procedures while the group of comparison consisted of 88
      (23.5%) patients treated othrerwise. The method in question included the
      microcurrent lymphatic drainage, the magneto-laser treatment, and
      ultraphonophoresis. The data obtained give evidence of the significant
      differences between the two groups of the patients in terms of reduction of
      oedema of the nasal and facial soft tissues on days 10-12 and 30-35 after the
      treatment as well as of subcutaneous hemorrhage and pain in the external nose on
      days 10-12. These effects were more pronounced in the patients of the main group.
      The local subcutaneous compaction was documented in both groups (though it was
      more pronounced in the patients of the comparison group; p<0.05) after the
      disappearance of the bulk of the swelling approximately on days 10-12. It is
      concluded that the results of the study confirm the effectiveness of the staged
      performance of various physiotherapeutic procedures during the postoperative
      period after rhinoplasty.

PMID- 29072663
TI  - [The effectiveness of the combination of azelastine hydrochloride and mometasone
      furoate for the intranasal application in the patients presenting with seasonal
      allergic rhinitis].
AB  - The objective of the present work was to evaluate the effectiveness of the
      combination of azelastine hydrochloride and mometasone furoate for the intranasal
      application to treat the patients presenting with seasonal allergic rhinitis. A
      total of 60 subjects suffering from seasonal allergic rhinitis were available for
      the observation. All the patients were allocated to three groups comprised of 20
      individuals each. The patients of the first group received the fixed combination
      of azelastine hydrochloride and mometasone furoate for the intranasal
      application, those in the second group were given mometasone furoate administered
      intranasally together with an oral antihistamine preparation of the third
      generation, and the patients of the third group were treated with intranasal
      mometasone furoate alone. The effectiveness of the treatment was evaluated on
      days 7 and 14 after its initiation. It was found that the treatment with the use
      of the combination of azelastine hydrochloride and mometasone furoate resulted in
      a more pronounced alleviation of rhinological symptoms and improvement of the
      quality of life at the early stages of therapy in comparison with mometasone
      furoate monotherapy. It is concluded that the patients with moderate and severe
      seasonal allergic rhinitis can be recommended to use the combination of
      azelastine hydrochloride and mometasone furoate as kachestve the initial
      treatment.

PMID- 29072664
TI  - [The application of different non-steroidal anti-inflammatory drugs for the
      elimination of pain syndrome during the early postoperative period in the
      children following the surgical interventions on palatine tonsils].
AB  - The present clinical study included 120 children at the age varying from 6 to 18
      tears who had undergone radiowave tonsillotomy followed by symptomatic therapy
      during the early postoperative period with the application of different non
      steroidal anti-inflammatory drugs. All the patients were randomly allocated to
      four groups each comprised of the equal number of patients. Those of group 1 were
      treated with ketoprofen lysine salt (KLS) in the form of a solution for oral
      intake in case of complaints of severe pain in the throat. The patients of group
      2 received courses of ketoprofen lysine salt therapy per os thrice daily during 3
      days after the surgical intervention. The patients of group 3 were given
      ibuprofen per os up to three times every day in case of complaints of severe pain
      in the throat. The patients of group 4 were treated with ketoprofen lysine salt
      in the form of a solution for the local application twice daily during 3 days
      after the surgical intervention. The results of the analysis with the use of the
      analog-visual scale have demonstrated that a decrease in pain intensity within 24
      hours after surgery was much more pronounced in the patients of group 2 in
      comparison with those of the remaining three groups (r<0.05). The difference of
      pain intensity in the throat evaluated based on the analog-visual scale between
      the patients of groups 1, 3, and 4 was insignificant (p>0.05). None of the
      children exhibited the signs of bleeding throughout the entire observation
      period. It can be concluded that a course of therapy with the use of ketoprofen
      lysine salt for oral intake during the early period after the surgical
      intervention for radiowave palatine tonsillotomy has some advantages over a
      single intake of the analogous preparation (for alleviation of strong pain in the
      throat), an ibuprofen syrup or a ketoprofen lysine salt solution for throat wash.

PMID- 29072665
TI  - [Granulomatosis with polyangiitis associated with the cytoplasmic antineutrophil
      antibodies].
AB  - The objective of the present work was to analyze the clinical case of
      granulomatosis with polyangiitis associated with the presence of cytoplasmic
      antineutrophil antibodies. We considered the medical records of the patient
      presenting with this condition. It was shown that systemic vasculitis had a
      polymorphic clinical picture; its diagnostics and treatment encountered serious
      difficulties. It is concluded that the development of progressive perforation of
      the nasal septum and destructive changes in the intranasal and adjacent
      structures after the endonasal surgical intervention implies the necessity of the
      detailed analysis of the clinical and laboratory observations with the subsequent
      counselling by a rheumatologist and oncologist for the clarification of the
      diagnosis and the choice of adequate therapy.

PMID- 29072666
TI  - [A clinical observation of an extensive chondroma of oro- and laryngopharynx].
AB  - This article was designed to report a rare case of oropharyngeal chondroma in a
      31 year-old male patient. Computed tomography revealed an encapsulated cystic
      solid tissue mass having the clear-cut contours with multiple diffuse foci of
      calcification in the tissue thickness. The neoplasm was morphologically
      characterized as a chondroma. The tumour was removed with the use of the modified
      Lauers-Balon procedure with the dissection of the lower jaw.

PMID- 29072668
TI  - [Polypous pansinusitis with the deformation of the external nose in a 8 year-old
      child presenting with the primary ciliary dyskinesia syndrome].
AB  - This article reports a rare observation of the development of chronic polypous
      pansinusitis with deformation of the external nose in a 8 year-old child
      presenting with primary ciliary dyskinesia syndrome. The patient underwent
      multiple surgical interventions in the preceding period. The key argument in
      favour of the definitive diagnosis was the results of investigation of ciliated
      epithelium biopsy taken from the nasal cavity and bronchi in combination with the
      data obtained by diagnostic endoscopy of the nasal cavity and nasopharynx
      supplemented by computed tomography. The proposed treatment strategy including
      endoscopic endonasal pansinusotomy, antibacterial therapy taking into
      consideration the sensitivity of the seeded microorganism, and hormonal therapy
      proved optimal for the management of the given patient.

PMID- 29072669
TI  - [Epithelial dysfunction associated with pyo-inflammatory diseases of the ENT
      organs].
AB  - The modern concept of epithelial-endothelial dysfunction and epithelial
      endothelial distress-syndrome associated with pyo-inflammatory ENT diseases is
      presented. It has provided a basis for the analysis of the initial stages of
      etiopathogenesis of acute and chronic inflammation in the ENT system including
      the mucous and associated lymphoid tissues as well as the Pirogov-Waldeyer
      limphopharyngeal ring making up the first protective barrier. The leading role of
      dysbiosis of synanthropic microflora and endotoxins of the Gram-negative bacteria
      in the mechanisms of regional responsiveness of the organism to the infection and
      chronic endotoxic aggression is demonstrated. The regional and synthetic
      mechanisms underlying the interaction between the external and internal media of
      the organism are subjected to the analysis with special reference to those
      operating in epithelium. The possible variants of the outcome of these processes
      are considered including both the recovery and the development of chronic
      inflammation. It has been proved that the exhaustion of the internal reserves for
      the stabilization of the epithelium-associated lymphoid tissue system including
      the Pirogov-Waldeyer limphopharyngeal ring leads to the formation of epithelial
      dysfunction as the initial stage of epithelial-endothelial dysfunction and
      epithelial-endothelial distress-syndrome. It is concluded that the modern concept
      of epithelial-endothelial dysfunction and epithelial-endothelial distress
      syndrome is a fundamental interdisciplinary phenomenon.

PMID- 29072667
TI  - [The surgical treatment of pyocele of the frontal sinus].
AB  - The authors describe a clinical case of pyocele of the frontal sinus in the
      patient presenting with polypous pansinisitis and pronouncd hypertrophy of the
      frontal sinuses with special reference to the specific features of diagnostics
      and surgical strategy for the treatment of this condition.

PMID- 29072670
TI  - [The genetic aspects of occupational hearing impairment].
AB  - This article was designed to be the overview of the current literature
      publications concerning the identification of the genetic markers of
      susceptibility to the noise-induced loss of hearing. The analysis of these data
      has demonstrated that the major gene polymorphisms associated with the
      development of this pathological condition are localized in the genes encoding
      for the antioxidant systems, potassium homeostasis, and adhesion molecules as
      well as in the genes involved in intercellular coupling, the mechanisms
      underlying the cellular response to stress, activation and regulation of heat
      shock proteins, and signaling function of the immune system. It is concluded that
      the further investigations into the genetic aspects of the full-genome sequencing
      techniques and the search for genomic associations could greatly contribute to
      the development of personalized medicine and the reduction of risks of
      occupational noise-induced sensorineural impairment of hearing.

PMID- 29072671
TI  - [The psychogenic hearing disorders in the children and adolescents].
AB  - The psychogenic loss of hearing is characterized by its impairment in the absence
      of anatomically and physiologically significant changes. These disorders are
      poorly represented in the scientific literature in comparison with the organic
      lesions. They are especially frequently overlooked in the children and
      adolescents. The objective of the present review was to analyze the literature
      publications concerning this problem and to report two clinical observations of
      the pathology in question. It is concluded that the clinically significant
      discrepancy between the audiological symptoms and the results obtained by the
      objective methods for hearing evaluation should be interpreted with great caution
      and raise the suspicion of the disease. The diagnosis and the identification of
      the involved psychogenic factors are of utmost importance for the success of the
      treatment.

PMID- 29072672
TI  - [The autoimmune rheumatic disease and laryngeal pathology].
AB  - Vocal disorders make up one of the autoimmune pathological conditions
      characterized by multiple organ system dysfunction. Laryngeal pathology in this
      condition has an autoimmune nature; it is highly diverse and poorly explored. The
      objective of the present work based on the analysis of the relevant literature
      publications was to study clinical manifestations of the autoimmune rheumatic
      disease affecting the larynx. 'Bamboo nodes' on the vocal folds is a rare
      manifestation of laryngeal autoimmune diseases. We found out references to 49
      cases of this condition in the available literature. All the patients were women
      presenting with autoimmune diseases. The present review highlights the problems
      pertaining to etiology of 'bamboo nodes' on the vocal folds and the method for
      the treatment of this condition.

PMID- 29072674
TI  - Comparison of Impedance and Pepsin Detection in the Laryngeal Mucosa to Determine
      Impedance Values that Indicate Pathological Laryngopharyngeal Reflux.
AB  - OBJECTIVE: Recently, a 24-h impedance was used to detect laryngopharyngeal reflux
      (LPR). However, not every case of LPR is pathological. Thus, pathological
      pharyngeal impedance values need to be clearly established to diagnose
      pathological LPR. The aim of our study was to establish pathological 24-h
      pharyngoesophageal impedance/pH values for the diagnosis of LPR. METHODS: The
      study was conducted in a tertiary care setting. A total of 30 patients who were
      referred to microlaryngoscopy for a laryngeal pathology that might be caused by
      LPR were included in this prospective study. All patients were off proton-pump
      inhibitor therapy. The 24-h pharyngoesophageal impedance-pH monitoring was
      performed 1 day before surgery. A biopsy of laryngeal tissue was obtained during
      microlaryngoscopy and was analyzed by immunohistochemistry to detect pepsin. The
      patients were divided into two groups: pepsin negative and pepsin positive (which
      indicated pathological LPR). The results of 24-h multichannel intraluminal
      impedance-dual-channel pH monitoring were compared between the groups. The number
      of LPR episodes in the pepsin-positive group was analyzed to establish a cutoff
      value for pathological LPR. RESULTS: There were 18 participants in the pepsin
      negative group and 12 in the pepsin-positive group. The median total pharyngeal
      refluxes detected were two (0-5) in the pepsin-negative group and 14 (6-39) in
      the pepsin-positive group (P<0.001), although the groups were otherwise
      homogeneous. There was a statistically significant difference in the number of
      all types of refluxes between groups. Six or more pharyngeal refluxes were the
      cutoff for the presence of pepsin in the laryngeal mucosa and, thereby, for the
      diagnosis of relevant/pathological LPR. CONCLUSION: Six or more pharyngeal reflux
      episodes registered during the 24-h impedance/pH monitoring seem to be the cutoff
      for diagnosing pathological LPR. Therefore, it is possible to suggest
      establishing this value as the pathological impedance value indicating
      pathological LPR. These results must be interpreted with caution due to the small
      sample size.

PMID- 29072673
TI  - Seven-Year Treatment Outcome of Entecavir in a Real-World Cohort: Effects on
      Clinical Parameters, HBsAg and HBcrAg Levels.
AB  - OBJECTIVES: We aimed to determine the levels of alanine aminotransferase (ALT),
      hepatitis B virus DNA (HBV DNA), HBsAg, and a novel viral marker (hepatitis B
      core-related antigen (HBcrAg)); hepatitis B e antigen (HBeAg) seroconversion and
      drug resistance rates after 7 years of entecavir treatment in chronic hepatitis B
      (CHB) patients. METHODS: Two hundred and twenty-two Chinese CHB patients on
      continuous entecavir treatment were recruited. Serologic, virologic, biochemical
      outcomes, and the occurrence of entecavir signature mutations were determined.
      RESULTS: The rates of ALT normalization, HBeAg seroconversion, and undetectable
      HBV DNA were 98.3%, 82.1%, and 98.7%, respectively, after 7 years of entecavir
      treatment. The genotypic resistance rate was 1.2%. Decline of HBsAg level was
      modest with a median decline rate of 0.107 log IU/ml/year. Among patients with
      baseline HBsAg <1,000 IU/ml and annual HBsAg decline rate of >=0.166 log IU/ml,
      all have HBsAg of <200 IU/ml (a level highly predictive for HBsAg seroclearance)
      at year 7. In contrast, in patients with baseline HBsAg >=1,000 IU/ml and annual
      HBsAg decline rate of <0.166 log IU/ml, 95.5% had HBsAg of >=200 IU/ml at year 7.
      Decline of HBcrAg levels was moderate with a median decline rate of 0.244 log
      kU/ml/year. Forty-seven patients (32.0%) had undetectable HBcrAg level at year 7.
      CONCLUSIONS: Long-term entecavir therapy continued to have good responses with
      low drug resistance rate. However, the decline of HBsAg with treatment was
      suboptimal. HBcrAg level declined at a relatively better rate. Baseline HBsAg
      level of <1,000 IU/ml and annual decline of 0.166 log IU/ml could be used to
      predict HBsAg response.

PMID- 29072676
TI  - Comparison of sprinting vs non-sprinting to wean nasal continuous positive airway
      pressure off in very preterm infants.
AB  - OBJECTIVE: Though nasal continuous positive airway pressure (NCPAP) is commonly
      used for non-invasive neonatal respiratory support, the optimal method of weaning
      NCPAP is not established. In this prospective, two-center randomized control
      trial we hypothesize that gradually increasing spontaneous breathing time off
      NCPAP increases successful weaning from NCPAP in infants born <31 weeks
      gestational age. STUDY DESIGN: Infants were randomized to one of the two NCPAP
      weaning protocols, a sprinting, that is, gradually increasing spontaneous
      breathing time off CPAP, protocol vs a non-sprinting (weaning pressure down)
      protocol. RESULT: Eighty-six infants were enrolled in one of the two study
      groups. Thirty-one infants (77%) in the sprinting group and 30 (75%) in the non
      sprinting group were successfully weaned off NCPAP at the first attempt (P>0.05).
      It took 1.3 (1 to 1.75) (median (IQR)) attempts and 7 (7 to 7) days to wean NCPAP
      off in the sprinting group vs 1.3 (1 to 1.75) attempts and 7 (7 to 10) days in
      the non-sprinting group (P>0.05). Additionally, no differences in the secondary
      outcomes of bronchopulmonary dysplasia, severe retinopathy of prematurity (?stage
      3), periventricular leukomalacia and length of stay were noted between the two
      groups. CONCLUSION: Weaning NCPAP via sprinting or non-sprinting protocol is
      comparable, not only for successful weaning but also for the occurrence of common
      neonatal morbidities that impact the long-term outcome in premature infants
      (ClinicalTrials.gov number, NCT02819050).

PMID- 29072677
TI  - The impact of neurally adjusted ventilatory assist mode on respiratory severity
      score and energy expenditure in infants: a randomized crossover trial.
AB  - OBJECTIVE: Examine respiratory severity scores (RSS) (mean airway pressure *
      fraction of inspired oxygen) and resting energy expenditure (REE) on neurally
      adjusted ventilatory assist (NAVA) compared with synchronized intermittent
      mandatory ventilation with pressure controlled and supported breath (SIMV
      (PC)PS). STUDY DESIGN: A randomized, crossover trial in a level IV neonatal
      intensive care unit. Twenty-four patients were ventilated with NAVA or SIMV (PC)
      PS for 12 h and then crossed over to the alternative mode for 12 h. The primary
      outcome (RSS) and additional secondary respiratory outcomes were analyzed.
      RESULTS: RSS and measured REE were not different between modes. On NAVA, peak
      inspiratory pressures were lower (17.8 vs 19.9 cmH2O (P<0.05)) without higher
      oxygen requirements. Respiratory rates were higher on NAVA (52 vs 39 (P<0.05)),
      estimated work of breathing (WOB) (0.01 vs 0.04 J l-1 (P<0.05)) was improved.
      CONCLUSION: NAVA mode can be safe without increase in RSS or REE. Although
      respiratory rates were higher, this was offset by lower peak inspiratory
      pressures and WOB during NAVA.

PMID- 29072675
TI  - Outcomes of prenatally diagnosed solitary functioning kidney during early life.
AB  - OBJECTIVE: To evaluate outcomes of congenital solitary functioning kidney (SFK)
      in early childhood. STUDY DESIGN: A retrospective study of 32 children diagnosed
      in utero with SFK owing to unilateral renal agenesis or multicystic dysplastic
      kidney and followed for 1 to 11.5 years. RESULTS: SFK length was in the
      compensatory hypertrophy range in 45% of fetal sonographic evaluations from mid
      pregnancy, and in 85% on postnatal follow-up. Glomerular filtration rate was
      below normal range in 44.4%, 12.5% and 0% at <1 year, age 1 to 3 years and
      thereafter, respectively. Hyperfiltration was detected in 18.5% and 82.6% at <1
      year and >3 years, respectively. Hypertension was documented in 35% at age 1 to 3
      years but in none at an older age. Proteinuria was absent in all children.
      CONCLUSION: Congenital SFK is apparently associated with little or no renal
      damage in infancy or childhood. Compensatory enlargement of the functioning
      kidney begins in utero and might serve as a prognostic indicator for normal renal
      function after birth.

PMID- 29072678
TI  - Specific detection of soluble EphA2 fragments in blood as a new biomarker for
      pancreatic cancer.
AB  - Because membrane type 1-matrix metalloproteinase 1 (MT1-MMP) and erythropoietin
      producing hepatocellular receptor 2 (EphA2) expression are upregulated by the
      Ras/mitogen-activated protein kinase pathway, they are frequently coexpressed in
      malignant tumors. MT1-MMP cleaves the N-terminal ligand-binding domain of EphA2
      and inactivates its ligand-dependent tumor-suppressing activity. Therefore,
      specific detection of the cleaved N-terminal EphA2 fragment in blood might be an
      effective biomarker to diagnose malignant tumors. To evaluate this possibility,
      we developed three monoclonal antibodies against the soluble EphA2 fragment. One
      of them recognized this fragment specifically, with negligible cross-reactivity
      to the intact form. We used the cleaved form-specific antibody to develop a
      quantitative enzyme-linked immunosorbent assay and confirmed the linear
      reactivity to the recombinant fragment. We applied this assay on commercially
      available serum specimens obtained from patients with several types of cancer
      including gastric, pancreatic, esophageal, gastroesophageal, and head-and-neck
      cancers, and healthy donors. Soluble EphA2 fragment levels in cancer-patient sera
      were higher than those in healthy donors (n=50). In particular, levels of eight
      out of nine (89%) pancreatic cancer patients and ten out of seventeen (59%)
      gastric cancer patients significantly exceeded cutoff values obtained from the
      healthy donors, whereas those of esophageal and head-and-neck cancer-patient sera
      were low. The preliminary receiver operating characteristic curve analysis for
      pancreatic cancer demonstrated that the sensitivity and specificity were 89.0%
      and 90.0%, respectively, whereas those of the conventional digestive tumor marker
      CA19-9 were 88.9% and 72.0%, respectively. These results indicated that specific
      detection of soluble EphA2 fragment levels in serum could be potentially useful
      as a biomarker to diagnose pancreatic cancer.

PMID- 29072679
TI  - ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells by
      NPRA/PGRMC1/EGFR complex and improves ovary functions of PCOS rats.
AB  - Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease
      characterized by polycystic ovaries, hyperandrogenism and anovulation. It is one
      of the main causes of infertility. RU486 is an antagonist of progesterone
      receptor, and most commonly used as a contraceptive. However, whether RU486 is
      correlated with PCOS remains unclear. Atrial natriuretic peptide (ANP) is a small
      peptide with natriuretic and diuretic functions, and its availability to be used
      in PCOS treatment is unknown. Here, we showed that the serum ANP level was lower
      in PCOS patients than that in healthy women, and it was also decreased in the
      serum and ovarian tissues of RU486-induced PCOS rats compared with the control
      rats. We also found that RU486 inhibited the proliferation and promoted the
      apoptosis of human KGN ovarian granulosa cells by downregulating progesterone
      receptor membrane component 1 (PGRMC1). Meantime, ANP promoted the proliferation
      and inhibited the apoptosis of KGN cells through upregulating ANP receptor A
      (NPRA). The promotive effects of ANP on ovarian functions were mediated through
      the formation of an NPRA/PGRMC1/EGFR complex, which further activated MAPK/ERK
      signaling and transcription factor AP1. Moreover, ANP treatment reversed the PCOS
      symptoms, and improved the fertility of RU486-induced PCOS rats. Collectively,
      these findings highlight that RU486 is associated with the pathogenesis of PCOS,
      and ANP treatment may be a promising therapeutic option for PCOS.

PMID- 29072680
TI  - Transglutaminase 2 mediates UV-induced skin inflammation by enhancing
      inflammatory cytokine production.
AB  - UV irradiation elicits acute inflammation in the skin by increasing
      proinflammatory cytokine production in keratinocytes. However, the downstream
      protein target(s) that link UV radiation to the activation of signaling pathways
      responsible for cytokine expression have not been fully elucidated. In this
      study, we report a novel role of transglutaminase 2 (TG2), a member of the TG
      enzyme family whose activities are critical for cornified envelope formation, in
      mediating UV-induced inflammation. Our results showed that TG2-deficient mice
      exhibited reduced inflammatory responses to UV irradiation, including reduced
      erythema, edema, dilation of blood vessels, inflammatory cell infiltration, and
      levels of inflammatory cytokines. Using primary mouse keratinocytes and HaCaT
      cells, we found that UV irradiation-induced cytokine production by activating
      TG2, but not by upregulating TG2 expression, and that ER calcium release
      triggered by the UV-induced activation of phospholipase C was required for TG2
      activation. Moreover, TG2 activity enhanced p65 phosphorylation, leading to an
      increase in NF-kappaB transcriptional activity. These results indicate that TG2
      is a critical mediator of cytokine expression in the UV-induced inflammatory
      response of keratinocytes, and suggest that TG2 inhibition might be useful for
      preventing UV-related skin disorders, such as photoaging and skin cancer caused
      by chronic UV exposure.

PMID- 29072681
TI  - Demethylzeylasteral inhibits cell proliferation and induces apoptosis through
      suppressing MCL1 in melanoma cells.
AB  - Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F,
      which plays important roles in multiple biological processes such as inflammation
      inhibition, as well as immunosuppression. However, anti-cancer function and the
      underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In
      this study, we demonstrate that demethylzeylasteral has an anti-tumor property in
      melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through
      cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells.
      MCL1 is an anti-apoptotic protein in BCL2 family, and amplifies frequently in
      multiple human cancers. MCL1 is also known as a potential contributor for the
      resistance of BCL2 inhibitors, as well as various chemotherapeutic drugs. MCL1
      is, therefore, regarded as a potential target for cancer therapy. Here, for the
      first time, we unveil that demethylzeylasteral suppresses the expression of MCL1.
      Interestingly, MCL1 interacts with S phase-related protein CDK2, and thereby
      inhibits it's ubiquitin-dependent degradation. Together, demethylzeylasteral is a
      promising anti-tumor compound in melanoma cells. Demethylzeylasteral is also a
      potential inhibitor of MCL1.

PMID- 29072682
TI  - C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to
      mumps virus infection induces male germ cell apoptosis.
AB  - Mumps virus (MuV) infection usually results in germ cell degeneration in the
      testis, which is an etiological factor for male infertility. However, the
      mechanisms by which MuV infection damages male germ cells remain unclear. The
      present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by
      mouse Sertoli cells in response to MuV infection, which induces germ cell
      apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3),
      a functional receptor of CXCL10, is constitutively expressed in male germ cells.
      Neutralizing antibodies against CXCR3 and an inhibitor of caspase-3 activation
      significantly inhibited CXCL10-induced male germ cell apoptosis. Furthermore, the
      tumor necrosis factor-alpha (TNF-alpha) upregulated CXCL10 production in Sertoli
      cells after MuV infection. The knockout of either CXCL10 or TNF-alpha reduced
      germ cell apoptosis in the co-cultures of germ cells and Sertoli cells in
      response to MuV infection. Local injection of MuV into the testes of mice
      confirmed the involvement of CXCL10 in germ cell apoptosis in vivo. These results
      provide novel insights into MuV-induced germ cell apoptosis in the testis.

PMID- 29072683
TI  - Plasminogen kringle 5 suppresses gastric cancer via regulating HIF-1alpha and
      GRP78.
AB  - Inhibition of tumour angiogenesis has an important role in antitumour therapy.
      However, a recent study indicates that antiangiogenesis therapy may lead to
      glucose-related protein 78 (GRP78) associated antiapoptotic resistance. The
      present study aims to elucidate the dual effects of plasminogen kringle 5 (K5) on
      tumour angiogenesis and apoptosis induction by targeting hypoxia-inducible factor
      1alpha (HIF-1alpha) and GRP78. Co-immunoprecipitation and western blotting were
      used for examining the ubiquitination of HIF-1alpha and analysing angiogenesis
      and apoptosis-associated proteins. K5 promoted the sumo/ubiquitin-mediated
      proteasomal degradation of HIF-1alpha by upregulating von Hippel-Lindau protein
      under hypoxia, resulting in the reduction of vascular endothelial growth factor
      and thus suppressing tumour angiogenesis. Furthermore, K5 decreased GRP78
      expression via downregulation of phosphorylated extracellular-regulated protein
      kinase, leading to caspase-7 cleavage and tumour cell apoptosis. Blocking voltage
      dependent anion channel abrogated the effects of K5 on both HIF-1alpha and GRP78.
      K5 significantly inhibited the growth of gastric carcinoma xenografts by
      inhibiting both angiogenesis and apoptosis. The dual effects suggest that K5
      might be a promising bio-therapeutic agent in the treatment of gastric cancer,
      particularly in patients who exhibit the induction of GRP78.

PMID- 29072685
TI  - SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and
      mitochondrial integrity.
AB  - Evidences of oxidative stress and mitochondrial dysfunction have been recognized
      in most of clinical and experimental liver diseases. SIRT3, a member of NAD+
      dependent deacetylases, is mainly localized in mitochondria. So far, the role of
      SIRT3 in protecting hepatocytes against oxidative stress remains elusive. Herein,
      we found SIRT3 protein expression is decreased in tert-butyl hydroperoxide (t
      BHP)-treated AML12 cells in vitro and primary hepatocytes from CCl4-injured mice
      in vivo. To further verify the role of SIRT3 in protecting hepatocytes from t-BHP
      induced injury, SIRT3 overexpressed AML12 cell line and primary hepatocytes were
      generated. SIRT3 overexpressed hepatocytes showed improved cell viability upon t
      BHP challenge, with less intracellular reactive oxygen species (ROS)
      accumulation. SIRT3 overexpression reduced superoxide dismutase 2 acetylation
      level and stimulated nuclear factor erythroid 2-related factor 2 nuclear
      translocation to enhance anti-oxidative capacity. Moreover, SIRT3 deacetylated
      peroxisome proliferator-activated receptor gamma coactivator 1alpha to promote
      mitochondrial biogenesis, and 8-oxoguanine DNA glycosylase 1 to orchestrate DNA
      repair, resulting in improved mitochondrial function. Through deacetylating Ku70,
      SIRT3 also abated mitochondrial translocation of dynamin-related protein 1, to
      attenuate mitochondrial fragmentation in t-BHP-injured hepatocytes. These results
      suggested that SIRT3 protected hepatocytes against oxidative stress by enhancing
      ROS scavenging and maintaining mitochondrial integrity.

PMID- 29072684
TI  - PLOD2 regulated by transcription factor FOXA1 promotes metastasis in NSCLC.
AB  - In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for
      cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2).
      The previous findings have demonstrated that the expression of PLOD2 was
      regulated by multiple factors, including HIF-1alpha, TGF-beta and microRNA-26a/b.
      Although PLOD2 was confirmed to be related to poor prognosis in lung
      adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung
      adenocarcinoma is poorly understood. On the other hand, upregulation or
      hyperactivation of epidermal growth factor receptor is considered as a prognostic
      marker in many cancers, especially in non-small-cell lung cancer (NSCLC). In this
      study, we found that PLOD2 was elevated in NSCLC specimens and positively links
      to NSCLC poor prognosis. Gain- and loss-of-function studies and orthotopic
      implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis
      directly by enhancing migration and indirectly by inducing collagen
      reorganization. In addition, we revealed that PLOD2 was regulated by PI3K/AKT
      FOXA1 axis. The transcription factor FOXA1 directly bound to the PLOD2 promoter,
      and turned on PLOD2 transcription. In summary, our findings revealed a regulatory
      mechanism of NSCLC metastasis through EGFR-PI3K/AKT-FOXA1-PLOD2 pathway, and
      provided PLOD2 as a therapeutic target for NSCLC treatment.

PMID- 29072686
TI  - Suppression of BMP-7 by histone deacetylase 2 promoted apoptosis of renal tubular
      epithelial cells in acute kidney injury.
AB  - Cisplatin, a highly effective and widely used chemotherapeutic agent, has a major
      limitation for its nephrotoxicity. Currently, there are no therapies available to
      treat or prevent cisplatin nephrotoxicity. We recently identified a novel
      strategy for attenuating its nephrotoxicity in chemotherapy by histone
      deacetylase (HDAC) inhibitors via epigenetic modification to enhance bone
      morphogenetic protein 7 (BMP-7) expression. Cisplatin upregulated the activity of
      HDAC2 in the kidney. Inhibition of HDAC with clinically used trichostatin A (TSA)
      or valproic acid (VPA) suppressed cisplatin-induced kidney injury and epithelial
      cell apoptosis. Overexpression of HDAC2 promotes CP-treated tubular epithelium
      cells apoptosis. Chromatin immunoprecipitation assay clearly detected HDAC2
      assosiation with BMP-7 promoter. Western blot and immunofluorescence results
      demonstrated that the expression of BMP-7 was clearly induced by TSA or VPA in
      vivo and in vitro. Interestingly, administration of recombinant BMP-7 (rhBMP-7)
      reduced cisplatin-induced kidney dysfunction. Moreover, BMP-7 treatment
      suppressed epithelial cell apoptosis and small interfering RNA-based knockdown of
      BMP-7 expression abolished HDAC inhibitors suppression of epithelial cell
      apoptosis in vitro. Results of current study indicated that TSA or VPA inhibited
      apoptosis of renal tubular epithelial cells via promoting the level of BMP-7
      epigenetically through targeting HDAC2. Hence, HDAC inhibitors could be useful
      therapeutic agents for the prevention of cisplatin nephrotoxicity.

PMID- 29072687
TI  - Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to
      suppress breast cancer cell invasion.
AB  - Guanylate-binding protein 2 (GBP2) is a member of the large GTPase superfamily
      that is strongly induced by interferon-gamma (IFN-gamma). Although the
      biochemical characteristics of GBP2 have been reported in detail, its biological
      function has not been thoroughly elucidated to date. To the best of our
      knowledge, this study presents the first demonstration that GBP2 inhibits
      mitochondrial fission and cell metastasis in breast cancer cells both in vitro
      and in vivo. Our previous work demonstrated that dynamin-related protein 1 (Drp1)
      dependent mitochondrial fission has a key role in breast cancer cell invasion. In
      this study, we demonstrate that GBP2 binds directly to Drp1. Elimination of Drp1
      by shRNA or Mdivi-1 (a Drp1-specific inhibitor) suppressed GBP2's regulatory
      function. Furthermore, GBP2 blocks Drp1 translocation from the cytosol to
      mitochondria, thereby attenuating Drp1-dependent mitochondrial fission and breast
      cancer cell invasion. In summary, our data provide new insights into the function
      and molecular mechanisms underlying GBP2's regulation of breast cancer cell
      invasion.

PMID- 29072688
TI  - MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma
      through targeting PAK5.
AB  - MicroRNA-106a-5p (MiR-106a-5p), a small non-coding RNA, has been reported to be
      downregulated in astrocytoma, osteosarcoma and colorectal cancer. However, the
      expression levels and biological function in renal cell carcinoma (RCC) have not
      been studied yet. In this study, we found that the miR-106a-5p was significantly
      downregulated in RCC tissues and cell lines, and that overexpression of miR-106a
      5p led to decreased cell metastasis ability in a xenograft model. Inhibition of
      miR-106a-5p in RCC cell lines altered the cell migration, invasion and wound
      healing abilities. Mechanistic studies demonstrated that miR-106a-5p directly
      bound to the 3'-UTR of the PAK5 mRNA and mediated a decrease in the protein
      expression of PAK5. We further proved that PAK5 protein levels were negatively
      correlated with the miR-106a-5p expression in both patient samples and xenograft
      model. In epigenetics, methylation specific PCR experiments indicated that the
      upstream gene promoter of miR-106a-5p was hypermethylated in RCC, which might be
      responsible for its downregulation. Our findings suggested that miR-106a-5p might
      be a potential gene therapy target for the treatment of RCC metastasis.

PMID- 29072689
TI  - MiR-629 promotes human pancreatic cancer progression by targeting FOXO3.
AB  - The FOXO signaling pathway has been reported to have an important role in human
      cancer. Expression of miR-629 was markedly upregulated in pancreatic cancer and
      negatively correlated with FOXO3. Therefore, exploring the regulatory mechanism
      of miR-629 and FOXO3 signaling may provide valuable clinical targets for
      pancreatic cancer therapy. In the current study, we found that overexpressing and
      inhibiting miR-629, respectively, enhanced and reduced the cell proliferation and
      metastasis of pancreatic cancer cells in vitro and in vivo compared with parental
      cells or cells transfected with a control vector. Furthermore, we found that miR
      629 negatively regulated FOXO3 protein expression and decreased the activity of a
      luciferase reporter construct containing the FOXO3 3'-untranslated region. These
      results show that miR-629 regulates FOXO3 at the posttranscriptional level,
      resulting in enhanced cell proliferation and invasion of pancreatic carcinoma.
      Furthermore, we found that overexpressing miR-629 enhanced, while inhibiting miR
      629 reduced, the stem cell-like phenotype of pancreatic cancer cells in vitro. A
      functional polymorphism at miR-629-binding site in the 3'-UTR of FOXO3 gene
      confers a decreased risk of progression in pancreatic carcinoma. Furthermore,
      these findings suggest that miR-629 has a vital role in promoting the development
      of pancreatic cancer and may represent a novel prognostic biomarker and
      therapeutic target.

PMID- 29072690
TI  - The non-invasive serum biomarker soluble Axl accurately detects advanced liver
      fibrosis and cirrhosis.
AB  - Soluble Axl (sAxl) was recently shown to be strongly released into the blood
      during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a
      biomarker of liver diseases. In this study we are the first to evaluate sAxl in
      human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient
      elastography (TE; Fibroscan) for its value to detect significant (F>=2), advanced
      fibrosis (F>=3), and cirrhosis (F4) in different liver disease etiologies and
      healthy controls. To properly determine the diagnostic accuracy of sAxl, a test
      cohort as well as a validation cohort was employed using liver biopsy as a
      reference method. Most notably, sAxl was confirmed to be an accurate biomarker of
      liver fibrosis and cirrhosis. Its accuracy was increased, if total serum albumin
      was added to build a sAxl/albumin ratio. Thereby an AUC of 0.763, 0.776, 0.826,
      and 0.832 was achieved corresponding to histological fibrosis stages F>=2, F>=3,
      F4 with liver biopsy as a reference method, and cirrhosis according to imaging
      techniques, respectively. With a cut-off of 1.29, a sensitivity, specificity,
      PPV, and NPV of 78.5%, 80.1%, 44%, 94.9% for the detection of cirrhosis was
      achieved. In comparison, ELF test and TE showed an AUC of 0.910, and 0.934,
      respectively, for the detection of cirrhosis. However, performance of TE was not
      possible in 14.4% of patients and both, ELFTM test and TE bear the disadvantage
      of high costs. In conclusion, the sAxl/albumin ratio is suggested as an accurate
      biomarker of liver fibrosis and cirrhosis. Due to its easy applicability and low
      costs it is suitable as screening parameter for significant to advanced liver
      fibrosis and cirrhosis, especially if TE is not available or not applicable.

PMID- 29072691
TI  - Phosphoprotein enriched in diabetes (PED/PEA15) promotes migration in
      hepatocellular carcinoma and confers resistance to sorafenib.
AB  - Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related death
      with limited treatment options and frequent resistance to sorafenib, the only
      drug currently approved for first-line therapy. Therefore, better understanding
      of HCC tumor biology and its resistance to treatment is urgently needed. Here, we
      analyzed the role of phosphoprotein enriched in diabetes (PED) in HCC. PED has
      been shown to regulate cell proliferation, apoptosis and migration in several
      types of cancer. However, its function in HCC has not been addressed yet. Our
      study revealed that both transcript and protein levels of PED were significantly
      high in HCC compared with non-tumoral tissue. Clinico-pathological correlation
      revealed that PEDhigh HCCs showed an enrichment of gene signatures associated
      with metastasis and poor prognosis. Further, we observed that PED overexpression
      elevated the migration potential and PED silencing the decreased migration
      potential in liver cancer cell lines without effecting cell proliferation.
      Interestingly, we found that PED expression was regulated by a hepatocyte
      specific nuclear factor, HNF4alpha. A reduction of HNF4alpha induced an increase
      in PED expression and consequently, promoted cell migration in vitro. Finally,
      PED reduced the antitumoral effect of sorafenib by inhibiting caspase-3/7
      activity. In conclusion, our data suggest that PED has a prominent role in HCC
      biology. It acts particularly on promoting cell migration and confers resistance
      to sorafenib treatment. PED may be a novel target for HCC therapy and serve as a
      predictive marker for treatment response against sorafenib.

PMID- 29072693
TI  - Corrigendum: NDRG1 inhibition sensitizes osteosarcoma cells to combretastatin A-4
      through targeting autophagy.
AB  - This corrects the article DOI: 10.1038/cddis.2017.438.

PMID- 29072692
TI  - miR-99a reveals two novel oncogenic proteins E2F2 and EMR2 and represses stemness
      in lung cancer.
AB  - Lung cancer is one of the most aggressive tumours with very low life expectancy.
      Altered microRNA expression is found in human tumours because it is involved in
      tumour growth, progression and metastasis. In this study, we analysed microRNA
      expression in 47 lung cancer biopsies. Among the most downregulated microRNAs we
      focussed on the miR-99a characterisation. In vitro experiments showed that miR
      99a expression decreases the proliferation of H1650, H1975 and H1299 lung cancer
      cells causing cell cycle arrest and apoptosis. We identified two novel proteins,
      E2F2 (E2F transcription factor 2) and EMR2 (EGF-like module-containing, mucin
      like, hormone receptor-like 2), downregulated by miR-99a by its direct binding to
      their 3'-UTR. Moreover, miR-99a expression prevented cancer cell epithelial-to
      mesenchymal transition (EMT) and repressed the tumourigenic potential of the
      cancer stem cell (CSC) population in both these cell lines and mice tumours
      originated from H1975 cells. The expression of E2F2 and EMR2 at protein level was
      studied in 119 lung cancer biopsies. E2F2 and EMR2 are preferentially expressed
      in adenocarcinomas subtypes versus other tumour types (squamous and others).
      Interestingly, the expression of E2F2 correlates with the presence of vimentin
      and both E2F2 and EMR2 correlate with the presence of beta-catenin. Moreover, miR
      99a expression correlates inversely with E2F2 and directly with beta-catenin
      expression in lung cancer biopsies. In conclusion, miR-99a reveals two novel
      targets E2F2 and EMR2 that play a key role in lung tumourigenesis. By inhibiting
      E2F2 and EMR2, miR-99a represses in vivo the transition of epithelial cells
      through an EMT process concomitantly with the inhibition of stemness features and
      consequently decreasing the CSC population.

PMID- 29072694
TI  - Calreticulin promotes EGF-induced EMT in pancreatic cancer cells via
      Integrin/EGFR-ERK/MAPK signaling pathway.
AB  - Our previous study showed that Calreticulin (CRT) promoted the development of
      pancreatic cancer (PC) through ERK/MAPK pathway. We next investigate whether CRT
      promotes EGF-induced epithelial-mesenchymal transition (EMT) in PC via
      Integrin/EGFR-ERK/MAPK signaling, which has not been reported yet to our
      knowledge. EGF simultaneously induced EMT and activated Integrin/EGFR-ERK/MAPK
      signaling pathway in 3 PC cells. However, CRT silencing significantly inhibited
      EGF function, including inhibiting EGF-induced EMT-like cell morphology, EGF
      enhanced cell invasion and migration, and EGF induced the decrease of E-cadherin,
      ZO-1, and beta-catenin and the increase of the key proteins in Integrin/EGFR
      ERK/MAPK signaling (pEGFR-tyr1173, Fibronectin, Integrinbeta1, c-Myc and pERK).
      Conversely, CRT overexpression rescued the change of EMT-related proteins induced
      by EGF in CRT silencing PC cells. Additionally, CRT was co-stained with pEGFR1173
      (with EGF), Fibronectin and Integrinbeta1 by IF under confocal microscopy and was
      co-immunoprecipitated with Fibronectin, Integrinbeta1 and c-Myc in both PC cells,
      all of which indicating a close interaction of CRT with Integrin/EGFR-ERK/MAPK
      signaling pathway in PC. In vivo, CRT silencing inhibited subcutaneous tumor
      growth and liver metastasis of pancreatic tumor. A positive relationship of CRT
      with Fibronectin, Integrinbeta1, c-Myc and pERK and a negative association of CRT
      with E-cad was also observed in vivo and clinical samples. Meanwhile,
      overexpression of the above proteins was closely associated with multiple
      aggressive clinicopathological characteristics and the poor prognosis of PC
      patients. CRT promotes EGF-induced EMT in PC cells via Integrin/EGFR-ERK/MAPK
      signaling pathway, which would be a promising therapy target for PC.

PMID- 29072695
TI  - Glucocorticoid mediates prenatal caffeine exposure-induced endochondral
      ossification retardation and its molecular mechanism in female fetal rats.
AB  - Our previous studies discovered that prenatal caffeine exposure (PCE) could
      induce intrauterine growth retardation (IUGR) and long-bone dysplasia in
      offspring rats, accompanied by maternal glucocorticoid over-exposure. This study
      is to explore whether intrauterine high glucocorticoid level can cause
      endochondral ossification retardation and clarify its molecular mechanism in PCE
      fetal rats. Pregnant Wistar rats were intragastrically administered 30 and 120
      mg/kg day of caffeine during gestational days (GDs) 9-20, then collected fetal
      serum and femurs at GD20. In vitro, primary chondrocytes were treated with
      corticosterone (0-1250 nM), caffeine (0-100 MUM), mitogen-inducible gene 6 (Mig
      6) siRNA and epidermal growth factor receptor (EGFR) siRNA, respectively, or
      together. Results showed that the hypertrophic chondrocytes zone (HZ) of PCE
      fetal femur was widened. Meanwhile, the expression levels of chondrocytes
      terminal differentiation genes in the HZ were decreased, and the chondrocytes
      apoptosis rate in the HZ was decreased too. Furthermore, PCE upregulated Mig-6
      and suppressed EGFR expression in the HZ. In vitro, a high-concentration
      corticosterone (1250 nM) upregulated Mig-6 expression, inhibit EGFR/c-Jun N
      terminal kinase (JNK) signaling pathway and terminal differentiation genes
      expression in chondrocytes and reduced cell apoptosis, and these above
      alterations could be partly reversed step-by-step after Mig-6 and EGFR knockdown.
      However, caffeine concentration dependently increased chondrocyte apoptosis
      without significant changes in the expression of terminal differentiation genes.
      Collectively, PCE caused endochondral ossification retardation in the female
      fetal rats, and its main mechanism was associated with glucocorticoid (rather
      than caffeine)-mediated chondrocyte terminal differentiation suppression by the
      upregulation of Mig-6 and then inhibition of EGFR/JNK pathway-mediated
      chondrocyte apoptosis.

PMID- 29072696
TI  - iASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non
      small-cell lung cancer.
AB  - Autophagy serves a critical function in the pathogenesis, response to therapy and
      clinical outcome in cancers. Although a recent report showed a role of iASPP in
      suppressing autophagy, its potential activity as a regulator of autophagy has not
      been investigated in lung cancer. Here we investigated the potential function and
      molecular mechanism of iASPP in mediating autophagy in human non-small-cell lung
      cancer. Our data suggested that forced expression of iASPP triggered autophagic
      flux, while inhibition of iASPP suppressed autophagy at the autophagsome
      formation stage in vitro. Furthermore, in vivo overexpression of iASPP in
      SCID/NOD mice promoted tumorigenesis and autophagy, with an increase in the
      conversion from LC3-I to LC3-II. The effects of iASPP were mediated through
      activation of mTOR pathway. Finally, cytoplasmic iASPP expression was upregulated
      in lung cancer patients, and was identified as an independent poor prognostic
      factor for lung cancer-specific death in patient samples. Taken together, our
      data showed that iASPP could promote tumor growth by increasing autophagic flux,
      and iASPP could serve as a poor prognostic factor and a potential therapeutic
      target in lung cancer.

PMID- 29072698
TI  - Circular RNA profiling reveals an abundant circLMO7 that regulates myoblasts
      differentiation and survival by sponging miR-378a-3p.
AB  - Circular RNAs (circRNAs) have been identified from various tissues and species,
      but their regulatory functions during developmental processes are not well
      understood. We examined circRNA expression profiles of two developmental stages
      of bovine skeletal muscle (embryonic and adult musculus longissimus) to provide
      first insights into their potential involvement in bovine myogenesis. We
      identified 12 981 circRNAs and annotated them to the Bos taurus reference genome,
      including 530 circular intronic RNAs (ciRNAs). One parental gene could generate
      multiple circRNA isoforms, with only one or two isoforms being expressed at
      higher expression levels. Also, several host genes produced different isoforms
      when comparing development stages. Most circRNA candidates contained two to seven
      exons, and genomic distances to back-splicing sites were usually less than 50 kb.
      The length of upstream or downstream flanking introns was usually less than 105
      nt (mean~11 000 nt). Several circRNAs differed in abundance between developmental
      stages, and real-time quantitative PCR (qPCR) analysis largely confirmed
      differential expression of the 17 circRNAs included in this analysis. The second
      part of our study characterized the role of circLMO7-one of the most down
      regulated circRNAs when comparing adult to embryonic muscle tissue-in bovine
      muscle development. Overexpression of circLMO7 inhibited the differentiation of
      primary bovine myoblasts, and it appears to function as a competing endogenous
      RNA for miR-378a-3p, whose involvement in bovine muscle development has been
      characterized beforehand. Congruent with our interpretation, circLMO7 increased
      the number of myoblasts in the S-phase of the cell cycle and decreased the
      proportion of cells in the G0/G1 phase. Moreover, it promoted the proliferation
      of myoblasts and protected them from apoptosis. Our study provides novel insights
      into the regulatory mechanisms underlying skeletal muscle development and
      identifies a number of circRNAs whose regulatory potential will need to be
      explored in the future.

PMID- 29072697
TI  - Requirement for CCNB1 in mouse spermatogenesis.
AB  - Spermatogenesis, which involves mitosis and meiosis of male germ cells, is a
      highly complicated and coordinately ordered process. Cyclin B1 (CCNB1), an
      important regulator in cell cycle machinery, is proved essential for mouse
      embryonic development. However, the role of CCNB1 in mammalian spermatogenesis
      remains unclear. Here we tested the requirement for CCNB1 using conditional
      knockout mice lacking CCNB1 in male germ cells. We found that ablation of CCNB1
      in gonocytes and spermatogonia led to mouse sterile caused by the male germ
      cells' depletion. Gonocyte and spermatogonia without CCNB1 is unable to
      proliferate normally and apoptosis increased. Moreover, CCNB1 ablation in
      spermatogonia may promote their differentiation by downregulating Lin28a and
      upregulating let-7 miRNA. However, ablation of CCNB1 in premeiotic male germ
      cells did not have an effect on meiosis of spermatocytes and male fertility,
      suggesting that CCNB1 may be dispensable for meiosis of spermatocytes.
      Collectively, these results indicate that CCNB1 is critically required for the
      proliferation of gonocytes and spermatogonia but may be redundant in meiosis of
      spermatocytes in mouse spermatogenesis.

PMID- 29072699
TI  - CITED2 affects leukemic cell survival by interfering with p53 activation.
AB  - CITED2 (CBP/p300-interacting-transactivator-with-an-ED-rich-tail 2) is a
      regulator of the acetyltransferase CBP/p300 and elevated CITED2 levels are shown
      in a number of acute myeloid leukemia (AML). To study the in vivo role of CITED2
      in AML maintenance, AML cells were transduced with a lentiviral construct for
      RNAi-mediated knockdown of CITED2. Mice transplanted with CITED2-knockdown AML
      cells (n=4) had a significantly longer survival compared to mice transplanted
      with control AML cells (P<0.02). In vitro, the reduction of CITED2 resulted in
      increased p53-mediated apoptosis and CDKN1A expression, whereas BCL2 levels were
      reduced. The activation of p53 upon CITED2 knockdown is not a direct consequence
      of increased CBP/p300-activity towards p53, since no increased formation of
      CBP/p300/p53 complexes was demonstrated and inhibition of CBP/p300-activity could
      not rescue the phenotype of CITED2-deficient cells. Instead, loss of CITED2 had
      an inhibitory effect on the AKT-signaling pathway, which was indicated by
      decreased levels of phosphorylated AKT and altered expression of the AKT-pathway
      regulators PHLDA3 and SOX4. Notably, simultaneous upregulation of BCL2 or
      downregulation of the p53-target gene PHLDA3 rescued the apoptotic phenotype in
      CITED2-knockdown cells. Furthermore, knockdown of CITED2 led to a decreased
      interaction of p53 with its inhibitor MDM2, which results in increased amounts of
      total p53 protein. In summary, our data indicate that CITED2 functions in
      pathways regulating p53 activity and therefore represents an interesting target
      for AML therapy, since de novo AML cases are characterized by an inactivation of
      the p53 pathway or deregulation of apoptosis-related genes.

PMID- 29072700
TI  - The spontaneous differentiation and chromosome loss in iPSCs of human trisomy 18
      syndrome.
AB  - Aneuploidy including trisomy results in developmental disabilities and is the
      leading cause of miscarriages in humans. Unlike trisomy 21, pathogenic mechanisms
      of trisomy 18 remain unclear. Here, we successfully generated induced pluripotent
      stem cells (iPSCs) from human amniotic fluid cells (AFCs) with trisomy 18
      pregnancies. We found that trisomy 18 iPSCs (18T-iPSCs) were prone to
      differentiate spontaneously. Intriguingly, 18T-iPSCs lost their extra 18
      chromosomes and converted to diploid cells after 10 generations. fluorescence in
      situ hybridization analysis showed chromosome loss was a random event that might
      happen in any trisomic cells. Selection undifferentiated cells for passage
      accelerated the recovery of euploid cells. Overall, our findings indicate the
      genomic instability of trisomy 18 iPSCs bearing an extra chromosome 18.

PMID- 29072701
TI  - Caspase-2 deficiency enhances whole-body carbohydrate utilisation and prevents
      high-fat diet-induced obesity.
AB  - Caspase-2 has been shown to be involved in metabolic homeostasis. Here, we show
      that caspase-2 deficiency alters basal energy metabolism by shifting the balance
      in fuel choice from fatty acid to carbohydrate usage. At 4 weeks of age, whole
      body carbohydrate utilisation was increased in Casp2-/- mice and was maintained
      into adulthood. By 17 weeks of age, Casp2-/- mice had reduced white adipose mass,
      smaller white adipocytes decreased fasting blood glucose and plasma triglycerides
      but maintained normal insulin levels. When placed on a 12-week high-fat diet
      (HFD), Casp2-/- mice resisted the development of obesity, fatty liver,
      hyperinsulinemia and insulin resistance. In addition, HFD-fed Casp2-/- mice had
      reduced white adipocyte hypertrophy, apoptosis and expansion of both subcutaneous
      and visceral adipose depots. Increased expression of UCP1 and the maintenance of
      adiponectin levels in white adipose tissue of HFD-fed Casp2-/- mice indicated
      increased browning and adipocyte hyperplasia. We found that while the preference
      for whole-body carbohydrate utilisation was maintained, HFD-fed Casp2-/- mice
      were not impaired in their ability to switch to utilising fats as a fuel source.
      Our findings suggest that caspase-2 impacts basal energy metabolism by regulating
      adipocyte biology and fat expansion, most likely via a non-apoptotic function.
      Furthermore, we show that caspase-2 deficiency shifts the balance in fuel choice
      towards increased carbohydrate utilisation and propose that this is due to mild
      energy stress. As a consequence, Casp2-/- mice show an adaptive remodelling of
      adipose tissue that protects from HFD-induced obesity and improves glucose
      homeostasis while paradoxically increasing their susceptibility to oxidative
      stress induced damage and premature ageing.

PMID- 29072702
TI  - A novel lnc-PCF promotes the proliferation of TGF-beta1-activated epithelial
      cells by targeting miR-344a-5p to regulate map3k11 in pulmonary fibrosis.
AB  - Emerging evidence suggests that microRNA (miRNA) and long noncoding RNA (lncRNA)
      play important roles in disease development. However, the mechanism underlying
      mRNA interaction with miRNA and lncRNA in idiopathic pulmonary fibrosis (IPF)
      remains unknown. This study presents a novel lnc-PCF that promotes the
      proliferation of TGF-beta1-activated epithelial cells through the regulation of
      map3k11 by directly targeting miR-344a-5p during pulmonary fibrogenesis.
      Bioinformatics and in vitro translation assay were performed to confirm whether
      or not lnc-PCF is an actual lncRNA. RNA fluorescent in situ hybridization (FISH)
      and nucleocytoplasmic separation showed that lnc-PCF is mainly expressed in the
      cytoplasm. Knockdown and knockin of lnc-PCF indicated that lnc-PCF could promote
      fibrogenesis by regulating the proliferation of epithelial cells activated by TGF
      beta1 according to the results of xCELLigence real-time cell analysis system,
      flow cytometry, and western blot analysis. Computational analysis and a dual
      luciferase reporter system were used to identify the target gene of miR-344a-5p,
      whereas RNA pull down, anti-AGO2 RNA immunoprecipitation, and rescue experiments
      were conducted to confirm the identity of this direct target. Further experiments
      verified that lnc-PCF promotes the proliferation of activated epithelial cells
      that were dependent on miR-344a-5p, which exerted its regulatory functions
      through its target gene map3k11. Finally, adenovirus packaging sh-lnc-PCF was
      sprayed into rat lung tissues to evaluate the therapeutic effect of lnc-PCF.
      These findings revealed that lnc-PCF can accelerate pulmonary fibrogenesis by
      directly targeting miR-344a-5p to regulate map3k11, which may be a potential
      therapeutic target in IPF.

PMID- 29072703
TI  - BCL6 attenuates renal inflammation via negative regulation of NLRP3
      transcription.
AB  - Renal inflammation contributes to the pathogeneses of hypertension. This study
      was designed to determine whether B-cell lymphoma 6 (BCL6) attenuates renal NLRP3
      inflammasome activation and inflammation and its underlying mechanism. Male
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were used in
      the present study. Angiotensin (Ang) II or lipopolysaccharides (LPS) was used to
      induce inflammation in HK-2 cells, a human renal tubular epithelial (RTE) cell
      line. NLRP3 inflammasome was activated and BCL6 was downregulated in the kidneys
      of SHR. Either Ang II or LPS suppressed BCL6 expression in HK-2 cells. BCL6
      overexpression in HK-2 cells attenuated Ang II-induced NLRP3 upregulation,
      inflammation and cell injury. The inhibitory effects of BCL6 overexpression on
      NLRP3 expression and inflammation were also observed in LPS-treated HK-2 cells.
      BCL6 inhibited the NLRP3 transcription via binding to the NLRP3 promoter. BCL6
      knockdown with shRNA increased NLRP3 and mature IL-1beta expression levels in
      both PBS- or Ang II-treated HK-2 cells but had no significant effects on ASC, pro
      caspase-1 and pro-IL-1beta expression levels. BCL6 overexpression caused by
      recombinant lentivirus expressing BCL6 reduced blood pressure in SHR. BCL6
      overexpression prevented the upregulation of NLRP3 and mature IL-1beta expression
      levels in the renal cortex of SHR. The results indicate that BCL6 attenuates Ang
      II- or LPS-induced inflammation in HK-2 cells via negative regulation of NLRP3
      transcription. BCL6 overexpression in SHR reduced blood pressure, NLRP3
      expression and inflammation in the renal cortex of SHR.

PMID- 29072704
TI  - Inhibition of Caspase-8 does not protect from alcohol-induced liver apoptosis but
      alleviates alcoholic hepatic steatosis in mice.
AB  - Hepatic apoptosis is involved in the progression of alcoholic liver disease
      (ALD). Caspase-8, the apical initiator in death receptor-mediated apoptosis, has
      been implicated in acute liver injury and in non-alcoholic steatohepatitis.
      However, the relevance of Caspase-8 in the pathogenesis of ALD remains unclear.
      In the present study, we investigated the impact of Caspase-8 in human and murine
      alcohol-induced apoptosis and in ALD. We investigated human samples from ALD
      patients, primary mouse hepatocytes, and hepatocyte-specific Caspase-8 knockout
      (Casp8Deltahepa) mice in acute and chronic models of ethanol (EtOH)
      administration. Caspase-8 activation was detected in liver biopsies from ALD
      patients, as well as in livers of wild-type (WT) mice after chronic ethanol
      feeding for 8 weeks using the Lieber-DeCarli model. Lack of Caspase-8 expression
      in Casp8Deltahepa animals failed to prevent alcohol-induced liver damage and
      apoptosis. Instead, inhibition of Caspase-8 shifted the ethanol-induced death
      signals towards pronounced activation of the intrinsic, mitochondria-dependent
      apoptosis pathway in Casp8Deltahepa livers involving enhanced release of
      cytochrome c, stronger Caspase-9 activation and specific morphological changes of
      mitochondria. In vitro and in vivo intervention using a pan-caspase inhibitor
      markedly attenuated alcohol-induced hepatocyte damage in a Caspase-8-independent
      manner. Surprisingly, EtOH-fed Casp8Deltahepa mice displayed significantly
      attenuated steatosis and reduced hepatic triglyceride and free fatty acids
      content. Caspase-8 is dispensable for alcohol-induced apoptosis, but plays an
      unexpected role for alcohol-dependent fat metabolism. We provide evidence that
      simultaneous inhibition of extrinsic and intrinsic apoptosis signaling using pan
      caspase inhibitors in vivo might be an optimal approach to treat alcohol-induced
      liver injury.

PMID- 29072705
TI  - MicroRNA-145 attenuates TNF-alpha-driven cartilage matrix degradation in
      osteoarthritis via direct suppression of MKK4.
AB  - Cartilage dyshomeostasis contributes to osteoarthritis (OA) pathogenesis, and
      tumor necrosis factor (TNF)-alpha has critical role in this process by driving
      inflammatory cascades and cartilage degradation. However, the negative regulation
      of TNF-alpha-mediated signaling remains undefined. Here we demonstrate the
      crucial role of miR-145 in the modulation of TNF-alpha-mediated signaling and
      cartilage matrix degradation. MicroRNA (miRNA) expression profiles of TNF-alpha
      stimulated chondrocytes showed that miR-145 expression was rapidly downregulated
      by TNF-alpha. Moreover, miR-145 was directly repressed by p65 and was negatively
      correlated with TNF-alpha secretion during OA progression. Further, we found that
      miR-145 directly targeted mitogen-activated protein kinase kinase 4 (MKK4) and
      broadly restrained the production of several TNF-alpha-triggered matrix-degrading
      enzymes (MMP-3, MMP-13, and Adamts-5). Mechanistic studies unveiled that miR-145
      negatively regulated TNF-alpha-mediated JNK and p38 activation, as well as the
      nuclear accumulation of p-c-Jun and p-ATF2, by inhibiting MKK4 phosphorylation,
      eventually resulting in the alteration of catabolic genes transcription. Indeed,
      p-ATF2 interacted with the promoter of Mmp-13, whereas p-c-Jun bound to promoters
      of Mmp-3 and Adamts-5. MKK4 was significantly elevated in OA cartilage.
      Eliminating MKK4 by short hairpin RNA resulted in obviously decreased matrix
      degrading enzymes production, JNK and p38 inactivation, and an inhibition of
      cartilage degradation. On the contrary, MKK4 overexpression enhanced TNF-alpha
      mediated signaling activation and transcription of downstream catabolic genes,
      and consequently worsened cartilage degradation. Moreover, intra-articular (IA)
      injection of miR-145 agonist to rat with surgery-induced OA alleviated cartilage
      destruction. Altogether, we elucidate a novel regulatory mechanism underlying TNF
      alpha-triggered cartilage degradation and demonstrate the potential utility of
      miR-145 and MKK4 as therapy targets for OA.

PMID- 29072706
TI  - Measuring protein structural changes on a proteome-wide scale using limited
      proteolysis-coupled mass spectrometry.
AB  - Protein structural changes induced by external perturbations or internal cues can
      profoundly influence protein activity and thus modulate cellular physiology. A
      number of biophysical approaches are available to probe protein structural
      changes, but these are not applicable to a whole proteome in a biological
      extract. Limited proteolysis-coupled mass spectrometry (LiP-MS) is a recently
      developed proteomics approach that enables the identification of protein
      structural changes directly in their complex biological context on a proteome
      wide scale. After perturbations of interest, proteome extracts are subjected to a
      double-protease digestion step with a nonspecific protease applied under native
      conditions, followed by complete digestion with the sequence-specific protease
      trypsin under denaturing conditions. This sequential treatment generates
      structure-specific peptides amenable to bottom-up MS analysis. Next, a proteomics
      workflow involving shotgun or targeted MS and label-free quantification is
      applied to measure structure-dependent proteolytic patterns directly in the
      proteome extract. Possible applications of LiP-MS include discovery of
      perturbation-induced protein structural alterations, identification of drug
      targets, detection of disease-associated protein structural states, and analysis
      of protein aggregates directly in biological samples. The approach also enables
      identification of the specific protein regions involved in the structural
      transition or affected by the binding event. Sample preparation takes
      approximately 2 d, followed by one to several days of MS and data analysis time,
      depending on the number of samples analyzed. Scientists with basic biochemistry
      training can implement the sample preparation steps. MS measurement and data
      analysis require a background in proteomics.

PMID- 29072707
TI  - The assembly and use of continuous flow systems for chemical synthesis.
AB  - The adoption of and opportunities in continuous flow synthesis ('flow chemistry')
      have increased significantly over the past several years. Continuous flow systems
      provide improved reaction safety and accelerated reaction kinetics, and have
      synthesised several active pharmaceutical ingredients in automated reconfigurable
      systems. Although continuous flow platforms are commercially available, systems
      constructed 'in-lab' provide researchers with a flexible, versatile, and cost
      effective alternative. Herein, we describe the assembly and use of a modular
      continuous flow apparatus from readily available and affordable parts in as
      little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4
      chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with
      an in-line quench is presented. This example reaction offers the opportunity to
      learn several important skills including reactor construction, charging of a back
      pressure regulator, assembly of stainless-steel syringes, assembly of a
      continuous flow system with multiple junctions, and yield determination. From our
      extensive experience of single-step and multistep continuous flow synthesis, we
      also describe solutions to commonly encountered technical problems such as
      precipitation of solids ('clogging') and reactor failure. Following this
      protocol, a nonspecialist can assemble a continuous flow system from reactor
      coils, syringes, pumps, in-line liquid-liquid separators, drying columns, back
      pressure regulators, static mixers, and packed-bed reactors.

PMID- 29072708
TI  - Preparation of glycoconjugates from unprotected carbohydrates for protein-binding
      studies.
AB  - Glycobiology, in particular the study of carbohydrate-protein interactions and
      the events that follow, has become an important research focus in recent decades.
      To study these interactions, many assays require homogeneous glycoconjugates in
      suitable amounts. Their synthesis is one of the methodological challenges of
      glycobiology. Here, we describe a versatile, three-stage protocol for the
      formation of glycoconjugates from unprotected carbohydrates, including those
      purified from natural sources, as exemplified here by rhizobial Nod factors and
      exopolysaccharide fragments. The first stage is to add an oligo(ethylene glycol)
      linker (OEG-linker) that has a terminal triphenylmethanethiol group to the
      reducing end of the oligosaccharide by oxime formation catalyzed by aniline. The
      triphenylmethyl (trityl) tag is then removed from the linker to expose a thiol
      (stage 2) to allow a conjugation reaction at the thiol group (stage 3). There are
      many possible conjugation reactions, depending on the desired application.
      Examples shown in this protocol are as follows: (i) coupling of the
      oligosaccharide to a support for surface plasmon resonance (SPR) studies, (ii)
      fluorescence labeling for microscale thermophoresis (MST) or bioimaging, and
      (iii) biotinylation for biolayer interferometry (BLI) studies. This protocol
      starts from unprotected carbohydrates and provides glycoconjugates in milligram
      amounts in just 2 d.

PMID- 29072709
TI  - Auditory fatigue among call dispatchers working with headsets.
AB  - OBJECTIVES: To determine whether call center dispatchers wearing headsets are
      subject to auditory fatigue at the end of a work shift. MATERIAL AND METHODS:
      Data was gathered at times when call centers were busiest. All call operators
      wore a headset for up to 12 h. Acoustic environment and noise exposure under the
      headset were continuously recorded during the entire work shift. Variations in
      auditory parameters were assessed using pure-tone air-conduction audiometry and
      an objective test based on distortion product otoacoustic emissions -
      contralateral suppression of distortion product otoacoustic emission (DPOAE)
      amplitudes (EchoScan test). Thirty-nine operators and 16 controls, all
      volunteers, were selected from 3 call centers (sales, assistance, and emergency)
      where all cognitive tasks were accomplished by phone and on computers. RESULTS:
      No acoustic shock was detected during the investigation. The highest normalized
      noise exposure (daily noise exposure level - L<sub>EX,8 h</sub>) measured was
      75.5 dBA. No significant variation in auditory performances was detected with
      either pure-tone air-conduction audiometry or the EchoScan test. Nevertheless,
      dispatchers expressed a feeling of tiredness. CONCLUSIONS: For an equivalent
      diffuse field noise exposure, the use of a headset does not seem to worsen
      auditory fatigue for call center operators. The dispatcher's fatigue was probably
      due to the duration of the work shift or to the tasks they performed rather than
      to the noise exposure under a headset. Int J Occup Med Environ Health
      2018;31(2):217-226.

PMID- 29072711
TI  - Seroprevalence of anti-HAV total antibodies among workers in wastewater treatment
      plants.
AB  - OBJECTIVES: Data on high frequency of hepatitis A virus (HAV) antibodies for
      wastewater treatment staff is contradictory. Literature lacks data on the
      seroprevalence of antibodies to HAV (anti-HAV) among workers in wastewater
      treatment plants (WWTPs) in Bulgaria. The aim of this study is to establish a
      specific humoral immune response to hepatitis A virus - anti-HAV total antibodies
      among staff in WWTPs. MATERIAL AND METHODS: A complex study of health and working
      conditions included 110 subjects working in 3 WWTPs in Bulgaria (74% of all
      workers in the 3 studied WWTPs and 20% of all employees in Bulgaria registered in
      2014 under the wastewater collection, discharge and treatment code of economic
      activity). Workers had been differentiated in 3 groups on the basis of their
      occupational work: operators, support staff and other workers exposed to
      biological agents. Venous blood from all 110 subjects was tested once for
      carriers of HAV antibodies. RESULTS: Anti-HAV total antibodies were found for
      52.7% of workers in WWTPs. There is a positive association between activity
      performed in WWTPs (operators, maintenance personnel and others exposed) and a
      positive one for the presence of anti-HAV (Chi<sup>2</sup> = 6.882, df = 2, p =
      0.032). Odds ratio (OR) for hepatitis A increases 2.9 times in the group of
      operators vs. others exposed to biological agents in WWTPs (OR = 2.914, 95%
      confidence interval (CI): 1.149-7.393, Fisher's p = 0.039). Odds ratio for
      hepatitis A increases 4.3 times in the group of support staff from WWTPs vs.
      others exposed to biological agents in WWTP (OR = 4.295, 95% CI: 1.075-17.167,
      Fisher's p = 0.049). CONCLUSIONS: Higher frequency of anti-HAV antibodies among
      operators and maintenance personnel at WWTPs has been established as compared to
      other workers exposed to biological agents in WWTPs. There is a positive
      association between increasing age of the workers and the presence of anti-HAV.
      Int J Occup Med Environ Health 2018;31(3):307-315.

PMID- 29072710
TI  - Economic situation and occupational accidents in Poland: 2002-2014 panel data
      regional study.
AB  - OBJECTIVES: Occupational accidents constitute a substantial health and economic
      burden for societies around the world and a variety of factors determine the
      frequency of accidents at work. The aim of this paper is to investigate the
      relationship between the economic situation and the rate of occupational
      accidents in Poland. MATERIAL AND METHODS: The analysis comprised data for 66
      Polish sub-regions taken from the Central Statistical Office's Local Data Bank.
      The regression analysis with panel data for period 2002-2014 was applied to
      identify the relationships involved. Four measures of accidents were used: the
      rates of total occupational accidents, accidents among men and women separately
      as well as days of incapacity to work due to accidents at work per employee. Four
      alternative measures assessed the economic situation: gross domestic product
      (GDP) per capita, average remuneration, the unemployment rate and number of
      dwelling permits. The confounding variables included were: employment in
      hazardous conditions and the size of enterprises. RESULTS: The results of the
      regression estimates show that the number of occupational accidents in Poland
      exhibits procyclical behavior, which means that more accidents are observed
      during the times of economic expansion. Stronger relationships were observed in
      the equations explaining men's accident rates as well as total rates. A weaker
      and not always statistically significant impact of economic situation was
      identified for women's accident rates and days of incapacity to work.
      CONCLUSIONS: The results have important implications for occupational health and
      safety actions. In the periods of higher work intensity employers should focus on
      appropriate training and supervision of inexperienced workers as well as on
      ensuring enough time for already experienced employees to recuperate. In terms of
      public health actions, policy makers should focus on scrutinizing working
      conditions, educating employers and counteracting possible discrimination of
      injured employees. Int J Occup Med Environ Health 2018;31(2):151-164.

PMID- 29072712
TI  - The determinants of lead and cadmium blood levels for preschool children from
      industrially contaminated sites in Poland.
AB  - OBJECTIVES: Industrially contaminated sites (ICS) represent an important public
      health issue in European countries. The Silesian Voivodeship, the region located
      in the southern part of Poland, the historical center of industry, has many sites
      that meet ICS criteria. Most of them are landfills containing lead, cadmium and
      zinc. MATERIAL AND METHODS: The aim of the study has been to evaluate
      determinants of lead and cadmium blood levels for preschool children living in
      the vicinity of selected environmental hazards in Piekary Slaskie, the city
      located in the region of Silesia. Data about exposure was obtained from the
      parental questionnaire and was verified by levels of biomarkers in children's
      blood. Finally, 678 preschool children were studied. RESULTS: Obtained results
      have confirmed that the statistically significant higher level of lead in blood
      has been revealed in the case of younger children whose fathers have a higher
      level of education and whose mothers smoke cigarettes at home, as well as for
      those living in the vicinity of any environmental hazard. In the case of cadmium,
      a higher level of the biomarker has been reported for older children who rather
      do not live close to any environmental hazard. We have recognized 30% of children
      with blood lead level (PbB) exceeding 2 MUg/dl and 0.8% of children with blood
      cadmium level (CdB) exceeding the reference value (0.5 MUg/l). CONCLUSIONS: Own
      observation has confirmed that preschool children living in Piekary Slaskie are
      still exposed to heavy metals existing in environment. The source of the higher
      level in blood is not only the hazardous vicinity in the place of residence but
      also well-known factors associated with the age of children, parental life style
      and educational background. The parental questionnaire could be useful to
      identify potential determinants of exposure to lead and cadmium, however exposure
      must be verified by measurement of a proper biomarker. Int J Occup Med Environ
      Health 2018;31(3):351-359.

PMID- 29072713
TI  - Leisure-time physical inactivity among healthcare workers.
AB  - OBJECTIVES: To estimate the prevalence of leisure-time physical inactivity (LTPI)
      and associated factors among healthcare workers. MATERIAL AND METHODS: The cross
      sectional study carried out with 2684 healthcare workers from 4 municipalities
      from the northeast region, Brazil. The LTPI was assessed by dichotomous question.
      The association between LTPI and the various independent variables was examined
      through the multinomial logistic regression analysis (crude and adjusted).
      RESULTS: The prevalence of LTPI was 47.9% (95% confidence interval (CI): 46.01
      48.80). The adjusted analysis (sociodemographic and occupational characteristics)
      showed that women and individuals with higher levels of education were more LTPI
      (p = 0.05). CONCLUSIONS: The prevalence of LTPI was high among the population
      investigated, especially among women and individuals with higher education. These
      results show the importance of developing actions to encourage adherence to
      physical activity during leisure time among workers, especially among the most
      vulnerable groups (people with higher education and women), given the benefits of
      this behavior to health. Int J Occup Med Environ Health 2018;31(3):251-260.

PMID- 29072714
TI  - Correction: Mapping the interaction sites of Mucin 1 and DNA aptamer by atomic
      force microscopy.
AB  - Correction for 'Mapping the interaction sites of Mucin 1 and DNA aptamer by
      atomic force microscopy' by Nan Wang, et al., Analyst, 2017, 142, 3800-3804.

PMID- 29072715
TI  - Sequential growth of CaF2:Yb,Er@CaF2:Gd nanoparticles for efficient magnetic
      resonance angiography and tumor diagnosis.
AB  - It is a significant challenge to develop nanoscale magnetic resonance imaging
      (MRI) contrast agents with high performance of relaxation. In this work, Gd3+
      doped CaF2-based core-shell nanoparticles (CaF2:Yb,Er@CaF2:Gd) of sub-10 nm size
      were controllably synthesized by a facile sequential growth method. The as
      prepared hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles modified using PEG-PAA di
      block copolymer benefited from the presence of Gd only in the outer CaF2 layer of
      the nanoparticles, which exhibited r1 as high as 21.86 mM-1 s-1 under 3.0 T,
      seven times as high as that of commercially used gadopentetate dimeglumine (Gd
      DTPA). Low cytotoxicity, no hemolysis phenomenon and no potential gadolinium ion
      leakage phenomenon of the hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles have been
      observed and confirmed. Clear vascular details can be observed in magnetic
      resonance angiography and obvious MR signal of 4T1 tumor area could be
      significantly improved by intravenous injection of the hydrophilic
      CaF2:Yb,Er@CaF2:Gd nanoparticles at a low dosage in mice. A series of in vivo
      biological safety evaluations confirmed the good biocompatibility of the
      hydrophilic CaF2:Yb,Er@CaF2:Gd nanoparticles, which might be employed in clinical
      blood pool imaging and tumor diagnosis as a safe and efficient MRI probe.

PMID- 29072716
TI  - Measurement of 14N quadrupole couplings in biomolecular solids using indirect
      detection 14N solid-state NMR with DNP.
AB  - The quadrupolar interaction experienced by the spin-1 14N nucleus is known to be
      extremely sensitive to local structure and dynamics. Furthermore, the 14N isotope
      is 99.6% naturally abundant, making it an attractive target for characterisation
      of nitrogen-rich biological molecules by solid-state NMR. In this study, dynamic
      nuclear polarization (DNP) is used in conjunction with indirect 14N detected
      solid-state NMR experiments to simultaneously characterise the quadrupolar
      interaction at multiple 14N sites in the backbone of the microcrystalline
      protein, GB3. Considerable variation in the quadrupolar interaction (>700 kHz) is
      observed throughout the protein backbone. The distribution in quadrupolar
      interactions observed reports on the variation in local backbone conformation and
      subtle differences in hydrogen-bonding; demonstrating a new route to the
      structural and dynamic analysis of biomolecules.

PMID- 29072719
TI  - Highly stereoselective cyclopropanation of various olefins with diazosulfones
      catalyzed by Ru(ii)-Pheox complexes.
AB  - A highly stereoselective cyclopropanation of various olefins with diazosulfones
      catalyzed by chiral Ru(ii)-Pheox complexes was developed to give chiral
      cyclopropyl sulfones in high yields (up to 99%) with excellent trans-selectivity
      and enantioselectivity (up to 98% ee).

PMID- 29072718
TI  - Field-effect sensors - from pH sensing to biosensing: sensitivity enhancement
      using streptavidin-biotin as a model system.
AB  - Field-Effect Transistor sensors (FET-sensors) have been receiving increasing
      attention for biomolecular sensing over the last two decades due to their
      potential for ultra-high sensitivity sensing, label-free operation, cost
      reduction and miniaturisation. Whilst the commercial application of FET-sensors
      in pH sensing has been realised, their commercial application in biomolecular
      sensing (termed BioFETs) is hindered by poor understanding of how to optimise
      device design for highly reproducible operation and high sensitivity. In part,
      these problems stem from the highly interdisciplinary nature of the problems
      encountered in this field, in which knowledge of biomolecular-binding kinetics,
      surface chemistry, electrical double layer physics and electrical engineering is
      required. In this work, a quantitative analysis and critical review has been
      performed comparing literature FET-sensor data for pH-sensing with data for
      sensing of biomolecular streptavidin binding to surface-bound biotin systems. The
      aim is to provide the first systematic, quantitative comparison of BioFET results
      for a single biomolecular analyte, specifically streptavidin, which is the most
      commonly used model protein in biosensing experiments, and often used as an
      initial proof-of-concept for new biosensor designs. This novel quantitative and
      comparative analysis of the surface potential behaviour of a range of devices
      demonstrated a strong contrast between the trends observed in pH-sensing and
      those in biomolecule-sensing. Potential explanations are discussed in detail and
      surface-chemistry optimisation is shown to be a vital component in sensitivity
      enhancement. Factors which can influence the response, yet which have not always
      been fully appreciated, are explored and practical suggestions are provided on
      how to improve experimental design.

PMID- 29072717
TI  - Stable isotope labeling by essential nutrients in cell culture (SILEC) for
      accurate measurement of nicotinamide adenine dinucleotide metabolism.
AB  - Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide
      phosphate (NADP) are conserved metabolic cofactors that mediate reduction
      oxidation (redox) reactions throughout all domains of life. The diversity of
      synthetic routes and cellular processes involving the transfer of reducing
      equivalents to and from these cofactors makes the accurate quantitation and
      metabolic tracing of NAD(H) and NADP(H) of broad interest. However, current
      analytical techniques typically rely on standard curves that do not incorporate
      confounding effects of the sample matrix. We utilized the essential requirement
      of niacin and tryptophan for NAD synthesis in mammalian cells to devise a stable
      isotope labeling by essential nutrients in cell culture (SILEC) method for
      efficient labeling of intracellular NAD(H) and NADP(H) pools. Coupling this
      approach with detection by liquid chromatography-high resolution mass
      spectrometry (LC-HRMS), we demonstrate the utility of incorporating a [13C315N1]
      nicotinamide moiety into a library of NAD-derived metabolites for use as internal
      standards in matrixed samples. Using a two-label system incorporating [13C315N1]
      nicotinamide and [13C11]-tryptophan, we quantify the relative contribution of
      salvage and de novo NAD synthesis, respectively, in S. cerevisiae and HepG2 human
      hepatocellular carcinoma cells under basal conditions. As a further proof-of
      principle, we demonstrate an improvement in the linear range for quantification
      of NAD and apply this method to analysis of NAD(H) in mouse liver. This method
      demonstrates the generalizability of SILEC, and provides a simple method for
      generating a library of stable isotope labeled internal standards for quantifying
      and tracing the metabolism of cellular and tissue NAD(H) and NADP(H).

PMID- 29072720
TI  - Cannabis through the looking glass: chemo- and enantio-selective separation of
      phytocannabinoids by enantioselective ultra high performance supercritical fluid
      chromatography.
AB  - By using the Inverted Chirality Columns Approach (ICCA) we have developed an
      enantioselective UHPSFC method to determine the enantiomeric excess (ee) of (-)
      Delta9-THC in medicinal marijuana (Bedrocan(r)). The ee was high (99.73%), but
      the concentration of the (+)-enantiomer (0.135%) was not negligible, and it is
      worth a systematic evaluation of bioactivity.

PMID- 29072721
TI  - Oxygen plasma treatment of HKUST-1 for porosity retention upon exposure to
      moisture.
AB  - Despite their remarkable properties, metal-organic frameworks (MOFs) present
      vulnerable structures that are sensitive to moisture; therefore, their
      application to real field situations is challenging. Herein, an O2 plasma
      technique was introduced as a new method for the activation and protection of
      porosity in HKUST-1. In an unprecedented manner, O2 plasma-treated HKUST-1
      retains its porosity after a long exposure to moisture as compared to pristine
      HKUST-1. Porosity retention was examined by N2 adsorption/desorption measurements
      of non-activated HKUST-1 after exposure to moisture.

PMID- 29072722
TI  - Exploiting electronic strategies to stabilize a planar tetracoordinate carbon in
      cyclic aromatic hydrocarbons.
AB  - A new approach to stabilize compounds containing a planar tetracoordinate carbon
      (ptC), embedded in aromatic hydrocarbons, is presented herein. This is achieved
      by using ligands that promote the formation of a 3c-2e sigma-bond with the ptC
      under two conditions: without altering the sp2 hybridization of the aromatic
      carbons; and containing empty orbitals perpendicular to the aromatic ring to
      participate in the aromatic pi-electronic delocalization.

PMID- 29072723
TI  - Silsesquioxane cages as fluoride sensors.
AB  - Pyrene functionalized silsesquioxane cages (PySQ) not only provide significant
      fluorescence from pyrene-pyrene excimers with a very large Stokes shift
      (Deltalambda = 143 nm, 69 930 cm-1) in DMSO but also exhibit fluoride capture
      results coincidentally with a pi-pi* fluorescence enhancement. On the other hand,
      PySQ-F- in THF significantly exhibits pi-pi* fluorescence quenching and a color
      change can be observed with the naked eye from light yellow to deep orange by
      forming a charge-transfer (CT) complex among the pyrenyl rings. Moreover, PySQ
      selectively captures F- with a response time of <2 min and with a very low
      detection limit (1.61 ppb), while 19F NMR is used to confirm encapsulation of F-
      with Deltadelta = 19 ppm.

PMID- 29072724
TI  - Bcl-XL-binding helical peptides possessing d-Ala residues at their C-termini with
      the advantage of long-lasting intracellular stabilities.
AB  - We attached d-Ala residues to cross-linked helical peptides based on the pro
      apoptotic protein Bad at their C-termini. The d-Ala attachment had little
      influence on the secondary structures and binding abilities against Bcl-XL. The d
      Ala attached helical peptides were much more stable in cells than original ones
      and efficiently induced apoptosis of the cells.

PMID- 29072726
TI  - Hydrophobic metallo-supramolecular Pd2L4 cages for zwitterionic guest
      encapsulation in organic solvents.
AB  - Hydrophilic zwitterionic guest encapsulation by metallo-supramolecular cages
      through synergetic coordination, H-bonding and hydrophobic interactions.

PMID- 29072728
TI  - Lead-free BNT-based composite materials: enhanced depolarization temperature and
      electromechanical behavior.
AB  - The development of (Bi0.5Na0.5)TiO3-based solid solutions with both high
      depolarization temperature Td and excellent piezoelectric and electromechanical
      properties for practical application is intractable because improved thermal
      stability is usually accompanied by a deterioration in piezoelectric and
      electromechanical performance. Herein, we report a 0-3 type 0.93(Bi0.5Na0.5)TiO3
      0.07BaTiO3 : 30 mol%ZnO composite (BNT-7BT : 0.3ZnO), in which the ZnO
      nanoparticles exist in two forms, to resolve the abovementioned long-standing
      obstacle. In this composite, Zn ions fill the boundaries of BNT-7BT grains, and
      residual Zn ions diffuse into the BNT-7BT lattice, as confirmed by XRD, Raman
      spectroscopy, and microstructure analysis. The BNT-7BT composite ceramics with a
      0-3 type connectivity exhibited enhanced frequency-dependent electromechanical
      properties, fatigue characteristics, and thermal stabilities. More importantly,
      low poling field-driven large piezoelectric properties were observed for the
      composite ceramics as compared to the case of the pure BNT-7BT solid solution. A
      mechanism related to the ZnO-driven phase transition from the rhombohedral to
      tetragonal phase and built-in electric field to partially compensate the
      depolarization field was proposed to explain the achieved outstanding
      piezoelectric performance. This is the first time that the thermal stability,
      electromechanical behavior, and low poling field-driven high piezoelectric
      performance of BNT-based ceramics have been simultaneously optimized. Thus, our
      study provides a referential methodology to achieve novel piezoceramics with
      excellent piezoelectricity by composite engineering and opens up a new
      development window for the utilization of conventional BNT-based and other lead
      free ceramics in practical applications.

PMID- 29072729
TI  - Molecular field theory for biaxial nematics formed from liquid crystal dimers and
      inhibited by the twist-bend nematic.
AB  - Liquid crystal dimers with odd spacers are good candidates as materials for
      biaxial nematic phases (NB). The dimers are flexible molecules sustaining biaxial
      conformations, and couplings between the conformational and orientational
      distributions could be expected to stabilise NB. We apply a molecular field
      theory for flexible molecules developed elsewhere to study a simple system made
      up of dimers composed of two cylindrically symmetric mesogenic groups. Our model
      allows for two idealised conformations: one linear and one bent at a tetrahedral
      angle. For a restricted set of chain lengths, the model predicts a first-order
      reentrant phase transition from the NB phase into a low temperature uniaxial
      nematic phase (NU). However the formation of the biaxial nematic could be blocked
      by the appearance of a twist-bent nematic.

PMID- 29072730
TI  - Photodissociation dynamics of fulvenallene and the fulvenallenyl radical at 248
      and 193 nm.
AB  - Photofragment translational spectroscopy was used to study the photodissociation
      of fulvenallene, C7H6, and the fulvenallenyl radical, C7H5, at 248 nm and 193 nm.
      Starting from fulvenallene, only the H-atom loss channel producing the
      fulvenallenyl radical, C7H5, was observed. Fulvenallene dissociation occurs on
      the ground state surface with no exit barrier, and there is good agreement
      between our experimentally determined photofragment translational energy
      distribution and a prior distribution for a statistical process. Subsequent
      absorption at both wavelengths by fulvenallenyl enabled investigation of the
      photodissociation of this radical. Two channels were observed: C5H3 + C2H2 and
      C4H2 + C3H3. The photofragment translational energy distributions for these
      channels are peaked away from 0 kcal mol-1, which is consistent with ground state
      dissociation over an exit barrier. At 248 nm, the C3H3-loss channel accounted for
      85 +/- 10% of fulvenallenyl dissociation, while at 193 nm it accounted for 80 +/-
      15%. The experimental branching between these channels is in reasonable agreement
      with Rice-Ramsperger-Kassel-Marcus theory calculations, which predict C3H3-loss
      to account for 70% and 63% of dissociation for 248 nm and 193 nm respectively.

PMID- 29072731
TI  - A chemical approach to perovskite solar cells: control of electron-transporting
      mesoporous TiO2 and utilization of nanocarbon materials.
AB  - Over the past several years, organometal halide perovskite solar cells (PSCs)
      have attracted considerable interest from the scientific research community
      because of their potential as promising photovoltaic devices for use in renewable
      energy production. To date, high power conversion efficiencies (PCEs) of more
      than 20% have been primarily achieved with mesoscopic-structured PSCs, where a
      mesoporous TiO2 (mTiO2) layer is incorporated as an electron-transporting
      mesoporous scaffold into the perovskite crystal, in addition to a compact TiO2
      (cTiO2) as an electron-transporting layer (ETL). In this Perspective, we first
      summarize recent research on the preparation strategies of the mTiO2 layer with a
      high electron transport capability by facile sol-gel methods instead of the
      conventional nanoparticle approach. The importance of the control of the pore
      size and grain boundaries of the mTiO2 in achieving high PCEs for PSCs is
      discussed. In addition, an alternative method to improve the electron transport
      in the mTiO2 layer via the incorporation of highly conductive nanocarbon
      materials, such as two-dimensional (2D) graphene and one-dimensional (1D) carbon
      nanotubes, is also summarized. Finally, we highlight the utilization of zero
      dimensional (0D) nanocarbon, i.e., fullerenes, as an n-type semiconducting
      material in mesostructure-free planar PSCs, which avoids high-temperature
      sintering during the fabrication of an ETL.

PMID- 29072734
TI  - Effects of Er3+ spatial distribution on luminescence properties and temperature
      sensing of upconverting core-shell nanocrystals with high Er3+ content.
AB  - In upconversion nanocrystals where Er3+ acts as the activator, concentration
      quenching will easily occur when the content of Er3+ is high (generally >5mol%),
      and the Er3+ spatial distribution which is a key factor affecting the
      concentration quenching is an important issue that must be considered. Herein, we
      selected Yb:NaErF4 as a light-emitting layer and investigated its upconversion
      performance and temperature sensing behaviors in two kinds of core-shell
      nanoarchitectures. Yb3+ and Er3+ activators were distributed in a three
      dimensional sphere and two-dimensional thin layer in Yb:NaErF4@Yb/Nd:NaYF4@NaGdF4
      and NaGdF4@Yb:NaErF4@Yb/Nd:NaYF4@NaGdF4 core-shell nanocrystals, respectively.
      The difference in Er3+ spatial distribution in the core-shell structure resulted
      in significant modification of red-to-green ratios and decay behaviors upon
      excitation at 376 nm, 808 nm, 980 nm and 1532 nm, and the related mechanisms were
      systematically investigated. In addition, the spatial distribution of Er3+ was
      demonstrated to have no obvious effect on the transitions of Er3+ thermally
      coupled 2H11/2 -> 4I15/2 and 4S3/2 -> 4I15/2 and the relative sensitivity for
      temperature determination under 808 nm laser excitation.

PMID- 29072735
TI  - Transparent Nb-doped TiO2 films with the [001] preferred orientation for
      efficient photocatalytic oxidation performance.
AB  - Doping and tailoring of the crystal orientation are two main strategies to
      improve the photocatalytic properties of TiO2 films. Herein, we introduce a novel
      route for obtaining Nb-doped TiO2 anatase films with the [001] preferred
      orientation by thermal oxidation of the [100]-oriented Nb-doped TiN film prepared
      by magnetron sputtering. Comprehensive analyses with X-ray diffraction, Raman
      scattering, high-resolution transmission electron microscopy, and X-ray
      photoelectron spectroscopy indicate that the proportion of high-energy (001)
      facets of the Nb-doped TiO2 film is more than 90% and the Nb5+ ion is
      successfully doped into the film without destroying the crystallinity and
      orientation. Moreover, the Nb5+ ion doping significantly restrains the growth of
      the TiO2 grains and increases the surface roughness, and consequently increases
      the surface-reactive sites. Therefore, the as-fabricated Nb-doped TiO2 film
      exhibits efficient photocatalytic oxidation performance for acetaldehyde and
      oleic acid decomposition under simulated solar light irradiation. Such Nb-doped
      TiO2 anatase films with high-reactivity (001) facet exposure may find
      applications in the photocatalysis and solar energy conversion fields.

PMID- 29072736
TI  - Tuning the flexibility of interpenetrated frameworks by a small difference in the
      fluorene moiety.
AB  - [Zn2(FDC)2(bpy)] (LMOF-202) and [Zn2(OFDC)2(bpy)] (LMOF-201) (FDC: fluorene-2,7
      dicarboxylate, OFDC: 9-fluorenone-2,7-dicarboxylate, bpy: 4,4'-bipyridine) have
      interpenetrated isostructures. However, their gas sorption behaviors indicate
      that LMOF-202 is rigid, whereas LMOF-201 is flexible. We found that the
      structural flexibility of LMOF-201 was due to the addition of only one oxygen
      atom into the ligand.

PMID- 29072738
TI  - Correlations in the elemental and metabolic profiles of the lichen Dirinaria
      picta after road traffic exposure.
AB  - Lichens can be used as cost-effective biomonitors of elements from road traffic
      in the urban environment. However, the nature of comprehensive interactions
      between hazardous heavy metals from road traffic and lichen metabolites remains
      unclear. In this study, elemental and metabolic profiles of the lichen Dirinaria
      picta after exposure to road traffic for 3 months in 9 sites of Singapore city
      were investigated. Concentrations of 34 elements reveal strong correlations among
      each other and a general increase with traffic exposure level. A variety of
      metabolites, i.e. sugar alcohols, sugars, amino acids, low-molecular mass organic
      acids, secondary metabolites and nucleosides, are identified through a multi
      platform approach combining liquid chromatography quadrupole time-of-flight mass
      spectrometry (LC-QTOF/MS), gas chromatography quadrupole mass spectrometry (GC
      Q/MS) and 1H nuclear magnetic resonance (1H NMR). The total amount of the heavy
      metals Fe, Zn, Cu, Cd, Pb and Co can be significantly correlated with 21
      metabolites positively and 9 metabolites negatively. These correlations reveal a
      heavy metal detoxification mechanism through ROS scavenging, osmoregulation and
      chelation with N atoms and sulfhydryl groups, as well as depletion of arabitol
      and inhibited synthesis of certain secondary metabolites such as quinones and
      steroids due to heavy metal stress. This study provides new insights into the
      metabolic toxicity and detoxification mechanisms in lichens under heavy metal
      exposure.

PMID- 29072739
TI  - Two-dimensional second-order nonlinear optical spectra: landscape of second-order
      nonlinear optics.
AB  - The landscape of second-order nonlinear optical (2nd NLO) responses of a system
      can be depicted as two-dimensional second-order nonlinear optical spectra in a
      range of external fields, and this is difficult to be realized in experiment for
      a wide range of external fields. In the present study, an efficient method for
      application of sum-over-states model to simulate electronic two-dimensional NLO
      (2DNLO) spectra has been developed, and techniques to analyze NLO response
      structure correlation have been proposed. This 2DNLO method has been applied to
      simulate the 2DNLO spectra of a series of typical electron push-pull chromophores
      under external fields of up to 5.00 eV. The correlation between the NLO
      properties and structure has been disclosed, and a further strategy to enhance
      the NLO properties of push-pull chromophores has been proposed.

PMID- 29072740
TI  - Ferritin nanocages loaded with gold ions induce oxidative stress and apoptosis in
      MCF-7 human breast cancer cells.
AB  - Two anticancer gold(iii) compounds, Au2phen and Auoxo4, were encapsulated within
      a ferritin nanocage. The gold-compound loaded proteins were characterized by UV
      Vis spectroscopy, inductively coupled plasma mass spectrometry and circular
      dichroism. X-ray crystallography shows that the compounds degrade upon
      encapsulation and gold(i) ions bind Ft within the cage, close to the side chains
      of Cys126. The gold-encapsulated nanocarriers are cytotoxic to human cancer
      cells. Au(i)-loaded Ft, obtained upon the encapsulation of Au2phen within the
      cage, induces oxidative stress activation, which finally leads to apoptosis in
      MCF-7 cells.

PMID- 29072741
TI  - An interaction network approach to study the correlation between endocrine
      disrupting chemicals and breast cancer.
AB  - Endocrine disrupting chemicals (EDCs) are natural or synthetic exogenous
      substances affecting human health. Although present at low concentrations in the
      environment, they can cause a broad range of negative effects on the endocrine
      functions by mimicking the action of steroid hormones due to their structural
      similarity. Hormonal unbalance can play an important role in carcinogenesis at
      any stage of disease. In the case of the breast cancer, EDCs directly affect the
      transformation of normal breast cells into cancer cells by interfering with
      hormonal regulation and by inducing the alteration of factors that regulate gene
      expression. The principal aims of this work were to study the interaction
      networks of proteins modulated in breast cancer by either environmental EDCs or
      mycotoxins, and to identify the proteins with the strongest coordination role
      defined as hub nodes. Our studies evidenced the presence of seven and six hub
      proteins in two EDCs and mycotoxins networks, respectively. Then, by merging the
      two networks, we identified that three hub nodes (BCL2, ESR2 and CTNNB1) in the
      environmental EDCs network show direct interactions with three hub nodes (CASP8,
      RELA and MKI67) in the mycotoxins network. These data highlighted that two
      networks are linked through proteins involved in the apoptosis regulation and in
      processes related to cell proliferation and survival, and, thus, in breast cancer
      progression.

PMID- 29072742
TI  - In silico modeling of protein hydrolysis by endoproteases: a case study on pepsin
      digestion of bovine lactoferrin.
AB  - This paper presents a novel model of protein hydrolysis and release of peptides
      by endoproteases. It requires the amino-acid sequence of the protein substrate to
      run, and makes use of simple Monte-Carlo in silico simulations to qualitatively
      and quantitatively predict the peptides that are likely to be produced during the
      course of the proteolytic reaction. In the present study, the model is applied to
      the case of pepsin, the gastric protease. Unlike pancreatic proteases, pepsin has
      a low substrate specificity and therefore displays a stochastic behavior that is
      particularly challenging to model and predict. Two versions of the model are
      studied and compared with peptidomic data obtained during pepsin hydrolysis of
      bovine lactoferrin. The first version of the model takes into account cleavage
      probabilities according to the amino acids in position P1-P1' only, whereas the
      second version also accounts for the influence of neighbor amino acids (P4, P3,
      P2, P2', P3', P4') and peptide terminal ends. The second version of the model was
      able to reproduce many real-world features of the reported behavior of pepsin,
      such as the peptide size distribution, or the quantity of free amino-acids. More
      remarkably, 50% of the experimentally monitored peptides (44/87) lay within the
      120 most abundant simulated peptides. The presented methodology has the advantage
      of being applicable not only to different proteins, but to different enzymes as
      well, as long as cleavage frequency data are available.

PMID- 29072743
TI  - A binder-free NiCo2O4 nanosheet/3D elastic N-doped hollow carbon nanotube sponge
      electrode with high volumetric and gravimetric capacitances for asymmetric
      supercapacitors.
AB  - To increase the volumetric and gravimetric capacitances of supercapacitors, a new
      class of electrode materials with high electrochemical activity and favorable
      structures is extremely desired. In this work, a hollow novel nitrogen-doped 3D
      elastic single-walled carbon nanotube sponge (NSCS) which is ultra lightweight
      with the lowest density of 0.8 mg cm-3, and has a high open surface structure for
      electrolyte accessibility and excellent compressible properties as the electrode
      scaffold has been successfully fabricated by the pyrolysis method which could
      produce the carbon nanotube sponge easily on a large scale without high-cost and
      time-consuming processes. Moreover, a NiCo2O4 nanosheet supported on the NSCS has
      been successfully fabricated. The highest volumetric and gravimetric capacitance
      of this electrode is 790 F cm-3 at 1.43 g cm-3 and 1618 F g-1 at 0.54 g cm-3 with
      excellent cycling stability. The density of NiCo2O4/NSCS electrode was adjusted
      by mechanical compression and the most favorable density of the film for both
      high volumetric and gravimetric capacitances obtained was 1.21 g cm-3. The thick
      NiCo2O4/NSCS film of 72 MUm has been fabricated at this favorable density,
      presenting both high volumetric and gravimetric capacitances of 597 F cm-3 and
      1074 F g-1 at 1 A g-1, respectively, indicating that the structure of the NSCS is
      extremely feasible for obtaining a thick film electrode with excellent volumetric
      and gravimetric capacitances. Furthermore, an asymmetric supercapacitor of
      NiCo2O4/NSCS//NGN/CNTs was fabricated, exhibiting a high gravimetric energy
      density of 47.65 W h kg-1 at 536 W kg-1 and a volumetric energy density of 33.44
      W h L-1 at 376.16 W L-1.

PMID- 29072744
TI  - Direct patterning of highly-conductive graphene@copper composites using copper
      naphthenate as a resist for graphene device applications.
AB  - We report an electron-beam lithography process to directly fabricate
      graphene@copper composite patterns without involving metal deposition, lift-off
      and etching processes using copper naphthenate as a high-resolution negative-tone
      resist. As a commonly used industrial painting product, copper naphthenate is
      extremely cheap with a long shelf time but demonstrates an unexpected patterning
      resolution better than 10 nm. With appropriate annealing under a hydrogen
      atmosphere, the produced graphene@copper composite patterns show high
      conductivity of ~400 S cm-1. X-ray diffraction, conformal Raman spectroscopy and
      X-ray photoelectron spectroscopy were used to analyze the chemical composition of
      the final patterns. With the properties of high resolution and high conductivity,
      the patterned graphene@copper composites could be used as conductive pads and
      interconnects for graphene electronic devices with ohmic contacts. Compared to
      common fabrication processes involving metal evaporation and lift-off steps, this
      pattern-transfer-free fabrication process using copper naphthenate resist is
      direct and simple but allows comparable device performance in practical device
      applications.

PMID- 29072745
TI  - Synthesis of highly stable quantum-dot silicone nanocomposites via in situ zinc
      terminated polysiloxane passivation.
AB  - Quantum dot (QD) silicone nanocomposites are promising luminescent materials for
      developing high performance light-emitting diodes (LEDs). However, their
      practical application still faces a critical issue of strong fluorescence
      quenching in commercial silicone, which is normally induced by the agglomeration
      of QDs and the impurities such as a Pt-catalyst and oxygen in the silicone
      matrices. This article reports the development of zinc-terminated
      polydimethylsiloxane (Zn-PDMS) to passivate CdSe/CdS/ZnS QDs via an in situ
      approach. The Zn-PDMS passivation protects the QDs from reacting with impurities
      and provides the mono-dispersion of QDs in silicone resin, leading to over 80%
      quantum efficiency as well as effective anti-quenching properties for the QD
      silicone nanocomposite under an ambient atmosphere. A high performance warm-white
      LED prototype with direct on-chip packaging using the as-prepared QDs is
      developed.

PMID- 29072746
TI  - Controlled synthesis of near-infrared quantum dots for optoelectronic devices.
AB  - We designed a facile approach for the synthesis of PbS quantum dots (QDs) using
      thiourea and lead acetate as sources of sulfur and lead, respectively. The sizes
      of the PbS QDs could be systematically controlled by simply adjusting the
      reaction parameters. Cd post-treatment via a cation exchange method was performed
      to increase the stability of QDs. As a proof of concept, colloidal PbS QDs
      synthesized by using air-stable thiourea were employed as light harvesters for
      both (i) solar driven photoelectrochemical (PEC) hydrogen generation and (ii) QDs
      sensitized solar cells (QDSSCs). For PEC hydrogen generation, similar saturated
      photocurrent densities are observed by using thiourea compared to
      bis(trimethylsilyl) sulfide, which is air-sensitive and unstable. For QDSSCs, the
      devices fabricated with QDs synthesized from thiourea reveal a better performance
      compared to devices fabricated with QDs synthesized from traditional
      bis(trimethylsilyl) sulfide. Our work demonstrates that this synthetic method is
      a promising alternative to the existing methodologies of PbS QDs and holds great
      potential for future solar technologies.

PMID- 29072748
TI  - Chemical vapor deposition of trigonal prismatic NbS2 monolayers and 3R-polytype
      few-layers.
AB  - Group VB transition-metal dichalcogenides (TMDs) have an intriguing structure
      dependent charge density wave and superconductivity. Here, we report the direct
      chemical vapor deposition of large-size NbS2 monolayers and few-layers with
      trigonal prismatic coordination and 3R polytype layer-layer stacking on hexagonal
      boron nitride (h-BN). The structure has been confirmed by micro-Raman
      spectroscopy and atomic-resolution scanning transmission electron microscopy
      (STEM).

PMID- 29072749
TI  - Multi-ligand-directed synthesis of chiral silver nanoclusters.
AB  - Engineering the surface ligands of metal nanoclusters is critical for tuning
      their sizes, structures and properties at the atomic level. Herein, we report the
      synthesis and total structure determination of [Ag32(Dppm)5(SAdm)13Cl8]3+ and
      [Ag45(Dppm)4(S-But)16Br12]3+ (where Dppm = bis(diphenyphosphino)methane, HSAdm =
      1-adamantanethiol and HS-But = tert-butyl mercaptan). The compositions of these
      two silver nanoclusters are determined by single-crystal X-ray diffraction (SC
      XRD) and X-ray photoelectron spectroscopy (XPS), respectively. Remarkably, the
      asymmetric distribution of the three types of ligands (thiolate, phosphine, and
      halogen) on the cluster surface is responsible for the chirality of the clusters.
      It is worth noting that these findings demonstrate the key principles of ligand
      shell anchoring for the tri-ligand protected silver clusters. Our work will offer
      further insights into the synthesis of chiral metal clusters by tailoring the
      surface ligands.

PMID- 29072750
TI  - Nanoscale, conformal films of graphitic carbon nitride deposited at room
      temperature: a method for construction of heterojunction devices.
AB  - Graphitic carbon nitrides (GCNs) represent a family of 2D materials composed of
      carbon and nitrogen with variable amounts of hydrogen, used in a wide variety of
      applications. We report a method of room temperature thin film deposition which
      allows ordered GCN layers to be deposited on a very wide variety of substrates,
      including conductive glass, flexible plastics, nanoparticles and nano-structured
      surfaces, where they form a highly conformal coating on the nanoscale. Film
      thicknesses of below 20 nm are achievable. In this way we construct functional
      nanoscale heterojunctions between TiO2 nanoparticles and GCN, capable of
      producing H2 photocatalytically under visible light irradiation. The films are
      hydrogen rich, have a band gap around 1.7 eV, display transmission electron
      microscopy lattice fringes as well as X-ray diffraction peaks despite being
      deposited at room temperature, and show characteristic Raman and IR bands. We use
      cluster etching to reveal the chemical environments of C and N in GCN using X-ray
      photoelectron spectroscopy. We elucidate the mechanism of this deposition, which
      operates via sequential surface adsorption and reaction analogous to atomic layer
      deposition. The mechanism may have implications for current models of carbon
      nitride formation.

PMID- 29072751
TI  - Visualization of periodic electric polarizability of helical nanofibers formed by
      self-assembly of nucleotide-bearing bolaamphiphiles and natural-source DNA as a
      template.
AB  - The possibility of fabricating DNA-based electronics has attracted considerable
      attention, but constructing robust, functional DNA nanowires on hard substrates
      has proven to be difficult. This paper describes the production of robust one
      dimensional nanofibers by self-assembly of 1,18-nucleotide-bearing
      bolaamphiphiles templated by salmon sperm DNA. Electrostatic force microscopy
      measurements of the nanofibers on a highly oriented pyrolytic graphite substrate
      revealed that they showed electric polarizability that varied periodically with a
      pitch of 20-30 nm. Atomic force microscopy, gel electrophoresis, and circular
      dichroism spectroscopy suggested that the periodic polarizability was derived
      from right-handed helicity induced by the template DNA. Salmon sperm DNA itself
      did not show electric polarizability.

PMID- 29072752
TI  - Nonequilibrium depletion interactions in active microrheology.
AB  - Entropic depletion forces arise between mesoscopic bodies that are immersed in a
      suspension of macromolecules, such as colloid-polymer mixtures. Here we consider
      the case of a driven colloidal probe in the presence of another, passive
      colloidal particle, both solvated in an ideal bath of small spherical particles.
      We calculate the nonequilibrium forces mediated by the depletants on the two
      colloidal particles within a dynamical superposition approximation (DSA) scheme.
      In order to assess the quality of this approximation, and to obtain the colloidal
      microstructure around the driven probe, we corroborate our theoretical results
      with Brownian dynamics simulations.

PMID- 29072753
TI  - Iron(iii)-catalyzed chelation assisted remote C-H bond oxygenation of 8
      amidoquinolines.
AB  - Iron catalyzed site selective and chelation assisted C-H functionalization in 8
      amidoquinolines is achieved. The remote C5-benzoxylation with benzoyl peroxide
      produced a variety of potentially bioactive 8-arylcarboxamido-5-benzoyloxy
      quinoline derivatives. The efficiency of the reaction reflects from the wide
      substrate scope with electronic differentiation on carboxamide and acyl peroxide
      in addition to tolerance of halo-substitutions on either of the aryls. The
      reaction is additive, silver free and proceeds without the exclusion of air or
      moisture.

PMID- 29072755
TI  - Ultraviolet erythema: dose response and mediator diffusion.
AB  - The earliest contribution made by Jan van der Leun to the field of photobiology
      was studying the mechanism of UV-induced erythema in human skin - a subject he
      chose for his PhD in the 1960s. His contribution to this topic encouraged us to
      continue this work and over a number of years in the 1980s and 1990s, we carried
      out several studies on quantitative aspects of UV erythema. A major part of Jan's
      thesis focused on diffusion processes in UV erythema and his observations led him
      to conclude that erythema induced by radiation with wavelengths of around 300 nm
      was due to the actions of a diffusing mediator arising in the epidermis, whereas
      radiation at shorter wavelengths around 254 nm, caused erythema by exerting a
      direct effect on the dermal blood vessels. By taking his data and combining them
      with our own studies on the dose response of UV erythema to radiation of
      different wavelengths, we were able to show that, contrary to Jan's conclusions,
      the mediator diffusion theory he developed did indeed predict that both UVB and
      UVC induced erythema could be explained by the action of diffusing mediators.

PMID- 29072754
TI  - Atomically dispersed Au catalysts supported on CeO2 foam: controllable synthesis
      and CO oxidation reaction mechanism.
AB  - CO oxidation is a typical heterogeneous catalytic reaction. Development of active
      and stable low-temperature CO oxidation catalysts has been one of the hot topics
      in the field of catalysis. In this work, we explored the catalytic application of
      a series of Au catalysts supported on CeO2 foam using a modified deposition
      precipitation method for CO oxidation. Among them, the catalyst with 1.1% Au
      loading content showed the highest catalytic activity, leading to the CO total
      conversion at 20  degrees C. Based on the strategy of stepwise reduction of Au
      loading content, we finally obtained the atomically monodisperse Au/CeO2 catalyst
      with high stability and strong resistance to elevated temperature, on which in
      situ DRIFTS analysis and DFT study were further performed to study the possible
      reactive site. Our results implied that the Au atoms on the CeO2 foam are the
      more stable sites for CO adsorption on the catalysts.

PMID- 29072757
TI  - Deposition of a titania layer on spherical porous silica particles and their
      nanostructure-induced vapor sensing properties.
AB  - A titania-stearic acid hybrid layer was deposited onto well-defined silica
      hexadecyltrimethylammonium hybrid spherical particles with 854 nm size to obtain
      nanoporous particles with a useful hierarchical core-shell structure. The
      deposition of a 35 nm-thick titania layer was confirmed by transmission electron
      microscopy. The core-shell particles were washed with acidic ethanol (solvent
      extraction) and calcined at 550  degrees C for 5 h to remove the template,
      resulting in the formation of nanoporous titania coated nanoporous silica
      spherical particles, which have a bimodal pore size distribution attributed to
      the hierarchical porous core and porous shell structure. The nanoporous titania
      coated particles exhibited an unusual crystal phase transition; only anatase was
      present even after the calcination at 1000  degrees C for 1 h. This would be due
      to the interfacial bonding between the core silica and the shell titania,
      preventing the crystal phase transition from anatase to rutile. On the other
      hand, the direct calcination of the titania-stearic acid coated particles without
      solvent extraction led to a shell composed of both anatase and rutile. The
      transformation to rutile could be caused by the strong exothermic reaction during
      the oxidative decomposition of the occluded stearic acid. Furthermore, the
      intense exothermic reaction induced the formation of a yolk-shell structure,
      which played a role in the sensitive/selective sensing properties for acetic acid
      when the yolk-shell particles were coated onto a nanomechanical Membrane-type
      Surface stress Sensor (MSS).

PMID- 29072756
TI  - Perfluorinated HDAC inhibitors as selective anticancer agents.
AB  - A series of potent histone deacetylase inhibitors is presented that incorporate
      alkyl or perfluorinated alkyl chains. Several new compounds show greater in vitro
      antiproliferative activity than the clinically approved inhibitor, SAHA.
      Furthermore, the new compounds show up to 5-fold greater activity against cancer
      cells than healthy cells. This selectivity is in contrast to SAHA, which is more
      active against the healthy cell line than the cancer cell line tested. Finally,
      we report an increase in activity for SAHA under mild hyperthermia, indicating
      that it could be an interesting candidate to use in combination with thermal
      therapy.

PMID- 29072760
TI  - Photodegradation of prednisolone under UVB solar irradiation. Role of
      photogenerated ROS in the degradation mechanism.
AB  - The use of biologically active substances with anti-inflammatory properties such
      as corticosteroids has increased considerably in the last few decades.
      Particularly, the compound we are interested in, prednisolone (Predn), is a
      glucocorticoid with high biological activity. This compound absorbs UV radiation
      and may participate in photochemical processes, which can result in its own
      decomposition. These processes could result in the formation of free radicals or
      reactive oxygen species (ROS). On these grounds, the kinetic and mechanistic
      aspects of the direct photodegradation of Predn have been studied in aqueous
      medium under different atmospheric conditions by stationary and time-resolved
      techniques. The mechanism involved in the photodegradation has been elucidated.
      Predn is capable of generating the excited triplet state 3Predn* as a result of
      UVB light absorption. In the presence of oxygen, 3Predn* allows the formation of
      ROS, of which O2(1Deltag) (PhiDelta = 0.014), H2O2 and the radical OH stand out.
      The latter is generated from the spontaneous dismutation of O2- and subsequent
      homolytic cleavage, photochemically promoted, of H2O2. Predn undergoes
      unimolecular photodegradation reactions under an inert argon atmosphere. In this
      study we found that in the presence of oxygen, the Predn photo-consumption is
      improved. This implies that the attack by ROS involves a very important
      additional contribution to the photodegradation of Predn under aerobic
      conditions.

PMID- 29072761
TI  - An amorphous Co-carbonate-hydroxide nanowire array for efficient and durable
      oxygen evolution reaction in carbonate electrolytes.
AB  - The development of earth-abundant catalysts toward high-efficient and durable
      oxygen evolution reaction (OER) electrocatalysis in the carbonate electrolyte is
      in great demand but remains a huge challenge. In this communication, we describe
      the development of a Co-carbonate-hydroxide nanowire array on nickel foam
      (CoCH/NF) via in situ electrochemical conversion of the Co(CO3)0.5(OH).0.11H2O
      nanowire array. When utilized as a 3D catalyst electrode for the OER in 1.0 M
      KHCO3 (pH: 8.3), as-formed CoCH/NF demands overpotential of only 332 mV to drive
      a geometrical catalytic current density of 10 mA cm-2, with its catalytic
      activity being maintained for at least 130 h. Impressively, it also demonstrates
      a high turnover frequency value of 0.22 mol O2 s-1 at an overpotential of 500 mV.

PMID- 29072762
TI  - Copper catalyzed oxidative homocoupling of terminal alkynes to 1,3-diynes: a
      Cu3(BTC)2 MOF as an efficient and ligand free catalyst for Glaser-Hay coupling.
AB  - A straightforward and efficient method has been demonstrated for the oxidative
      coupling of terminal alkynes using a simple Cu3(BTC)2-metal organic framework as
      a sustainable heterogeneous copper catalyst. A series of symmetrical 1,3-diynes
      bearing diverse functional groups have been synthesized in moderate to excellent
      yields via a Cu3(BTC)2 catalyzed Glaser-Hay reaction. The presence of the
      coordinatively unsaturated open CuII sites in Cu3(BTC)2 catalyzes the
      homocoupling in the presence of air, as an environment friendly oxidant without
      the use of external oxidants, ligands or any additives. The present methodology
      avoids stoichiometric reagents and harsher or special reaction conditions, and
      shows good functional group tolerance. The as-prepared catalyst could be
      separated easily by simple filtration and reused several times without any
      notable loss in activity. The hot filtration test has investigated the true
      heterogeneity of the catalyst. Additionally, the powder X-ray diffraction pattern
      of the reused catalyst revealed the high stability of the catalyst.

PMID- 29072763
TI  - Yolk-shell magnetic mesoporous TiO2 microspheres with flowerlike NiO nanosheets
      for highly selective enrichment of phosphopeptides.
AB  - In this work, we fabricated a yolk-shell magnetic composite that contains
      mesoporous TiO2 as the inner shell and flowerlike NiO as the outer shell (denoted
      as Fe3O4@H-TiO2@f-NiO) to reduce the limitations of single-component metal oxides
      in phosphopeptide enrichment. The NiO nanosheets play a synergistic role in
      phosphopeptide enrichment. And the unique flowerlike structure of NiO with
      sufficient space can facilitate the reversible insertion/extraction of peptides,
      which will have less impact on the enrichment process of the inner TiO2 shell.
      The yolk-shell structure and two types of porous nanostructures endowed this
      composite with a high surface area (156.58 m2 g-1) and a large pore volume (0.37
      cm3 g-1). Owing to the high surface area and combined properties of TiO2 and NiO,
      the Fe3O4@H-TiO2@f-NiO microspheres showed a better performance for
      phosphopeptide enrichment than the same material without NiO nanosheets (Fe3O4@H
      TiO2). According to the LC-MS/MS results, 972 unique phosphopeptides were
      identified from HeLa cell extracts with a high selectivity (91.9%) by Fe3O4@H
      TiO2@f-NiO relative to 837 phosphopeptides (selectivity: 60.2%) by Fe3O4@H-TiO2.
      The results demonstrated that, compared with single-component metal oxides,
      composite metal oxides could enhance the selectivity and sensitivity for
      phosphopeptide enrichment.

PMID- 29072764
TI  - Ground state instabilities of protein shells are eliminated by buckling.
AB  - We propose a hybrid discrete-continuum model to study the ground state of protein
      shells. The model allows for shape transformation of the shell and buckling
      transitions as well as the competition between states with different symmetries
      that characterize discrete particle models with radial pair potentials. Our main
      results are as follows. For large Foppl-von Karman (FvK) numbers the shells have
      stable isometric ground states. As the FvK number is reduced, shells undergo a
      buckling transition resembling that of thin-shell elasticity theory. When the
      width of the pair potential is reduced below a critical value, then buckling
      coincides with the onset of structural instability triggered by over-stretched
      pair potentials. Chiral shells are found to be more prone to structural
      instability than achiral shells. It is argued that the well-width appropriate for
      protein shells lies below the structural instability threshold. This means that
      the self-assembly of protein shells with a well-defined, stable structure is
      possible only if the bending energy of the shell is sufficiently low so that the
      FvK number of the assembled shell is above the buckling threshold.

PMID- 29072765
TI  - The cytochrome b5 CybE is regulated by iron availability and is crucial for azole
      resistance in A. fumigatus.
AB  - Cytochrome P450 enzymes (P450) play essential roles in redox metabolism in all
      domains of life including detoxification reactions and sterol biosynthesis. The
      activity of P450s is fuelled by two electron-transferring mechanisms, heme
      independent P450 reductase (CPR) and the heme-dependent cytochrome b5
      (CYB5)/cytochrome b5 reductase (CB5R) system. In this study, we characterised the
      role and regulation of the cytochrome b5 CybE in the fungal pathogen Aspergillus
      fumigatus. Deletion of the CybE encoding gene (cybE) caused a severe growth
      defect in two different A. fumigatus isolates, emphasising the importance of the
      CB5R system in this pathogen, while the non-essentiality of cybE indicates the
      partial redundancy of the CPR and CB5R systems. Interestingly, the growth defect
      caused by the cybE loss of function was even more drastic in A. fumigatus strain
      AfS77 compared to strain A1160P+ indicating a strain-dependent degree of
      compensation, which is supported by azole resistance studies. In agreement with
      CybE being important for the assistance of the ergosterol biosynthetic P450
      Cyp51, deletion of cybE decreased resistance to the Cyp51-targeting antifungal
      voriconazole and caused accumulation of the ergosterol pathway intermediate
      eburicol. Northern analysis indicated that CybE deficiency leads to the
      compensatory transcriptional upregulation of Cyp51-encoding cyp51A and CPR
      encoding cprA. Overexpression of cybE did not affect azole resistance suggesting
      that CybE activity is not rate limiting. Expression of cybE was found to be
      repressed during iron starvation by the iron-regulatory transcription factor HapX
      demonstrating iron dependence of CybE not only at the level of enzyme activity
      but also at the level of gene expression.

PMID- 29072766
TI  - The electron injection rate in CdSe quantum dot sensitized solar cells: from a
      bifunctional linker and zinc oxide morphology.
AB  - Herein, we have investigated the effect of both the bifunctional linker (L1, L2,
      L3, and L4) and ZnO morphology (porous nanoparticles (NPs), nanowires (NWs), and
      nanotubes (NTs-A and NTs-Z)) on the electron injection in CdSe QD sensitized
      solar cells by first-principles simulation. Via calculating the partitioned
      interfaces formed by different components (linker/QDs and ZnO/linker), we found
      that the electronic states of QDs and every ZnO substrate are insensitive to any
      linker, while the frontier orbitals of L1-L4 (with increased delocalization)
      manifest a systematical negative-shift. Because of the lowest unoccupied
      molecular orbital (LUMO) of L1 compared to its counterparts aligned in the region
      of the virtual states of QDs or the substrate with a high density of states, it
      always yields a stronger electronic coupling with QDs and varied substrates.
      After characterization of the complete ZnO/linker/QD system, we found that the
      electron injection time (tau) vastly depends on both the linker and substrate. On
      the one hand, L1 bridged QDs and every substrate always achieve the shortest tau
      compared to their counterpart associated cases. On the other hand, NW supported
      systems always yield the shortest tau no matter what the linker is. Overall, the
      NW/L1/QD system achieves the fastest injection by ~160 fs. This essentially stems
      from the shortest molecular length of L1 decreasing the distance between QDs and
      the substrate, subsequently improving the interfacial coupling. Meanwhile, the NW
      supported cases generate the less sensitive virtual states for both the QDs and
      NWs, ensuring a less variable interfacial coupling. These facts combined can
      provide understanding of the effects contributed from the linker and the oxide
      semiconductor morphology on charge transfer with the aim of choosing an
      appropriate component with fast directional electron injection.

PMID- 29072767
TI  - Biocompatible silver, gold and silver/gold alloy nanoparticles for enhanced
      cancer therapy: in vitro and in vivo perspectives.
AB  - The aims of nano oncology are to detect, target and treat cancer cells without
      any side effects. The present study describes the microbial synthesis of
      biocompatible nanoparticles of silver (AgNPs), gold (AuNPs) and their alloy
      (Ag/AuNPs) for hepatoprotective activity against diethylnitrosamine (DEN)-induced
      liver cancer in a Sprague Dawley (SD) rat model. The crystalline nature and
      physicochemical features of the nanoparticles were identified by Fourier
      transform infra-red (FT-IR) spectroscopy, X-ray diffraction (XRD), X-ray
      photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and
      selected area electron diffraction (SAED) analysis. Based on the instrumental
      analysis, the synthesised nanomaterials were found to be spherical in shape and
      have an average size in the nano region. Nitrate reductase was characterized
      after partial purification of the culture filtrate via polyacrylamide gel
      electrophoresis and its molecular weight was determined as ~45 kDa. Furthermore,
      the IC50 values of the AgNPs, AuNPs and Ag/AuNPs on HepG2 cells were determined
      as 38.42 MUg ml-1, 43.25 MUg ml-1 and 39.20 MUg ml-1, respectively, and the
      antioxidant potential of the nanoparticles was also systematically analyzed. The
      No-Observed-Adverse-Effect-Level (NOAEL) for the AgNPs was determined to be 2000
      mg per kg of body weight (bw) from an acute toxicity test. Similarly, the NOAEL
      of AuNPs and Ag/AuNPs were calculated as 1000 mg per kg bw. Based on the in vivo
      studies, a significant tumour reduction (~45 to 65%) was observed in the
      nanoparticle-treated animals, which was further confirmed by hematological,
      biochemical, TEM and histopathological analysis. Immunohistochemistry analysis
      confirmed the presence of BAX antibodies, up to immunoreactive (3+) level in
      treated animals. These results strongly suggest the potential anticancer
      activities of AgNPs, AuNPs and Ag/AuNPs against DEN-induced liver cancer and they
      could be potential candidates for effective nano drug development.

PMID- 29072768
TI  - Crystal polymorphism in polydiacetylene-embedded electrospun polyvinylidene
      fluoride nanofibers.
AB  - In this study, polydiacetylene (PDA) is embedded in electrospun polyvinylidene
      fluoride (PVDF) nanofibers for the preparation of mats with dual colorimetric and
      piezoelectric responses. The diacetylene monomers are self-assembled during the
      electrospinning process. The PDA-embedded PVDF nanofibers in the blue phase are
      obtained via photo-polymerization upon UV-light irradiation. The colorimetric
      transition of the nanofibers is studied as a function of temperature using a
      spectrophotometer. The morphology and crystal polymorphism of the nanofibers are
      investigated. The results show that the addition of PDA increases the diameter of
      the nanofibers due to the increase in the electrospinning solution viscosity. The
      results of Fourier transform infrared and wide angle X-ray diffraction
      demonstrate that PDA has the effect of inhibiting the growth of non-polar alpha
      phase crystals, while promoting the growth of the polar beta-phase. However, the
      red phase of PDA-embedded PVDF exhibits a lower intensity of the beta-phase in
      comparison to that of the blue phase. In fact, the blue-to-red color transition
      of the PDA-embedded electrospun PVDF nanofibers is accompanied by the variation
      of piezoelectric signaling caused by variations in the beta-phase. This
      phenomenon creates great potential in commercial detection sensors in addition to
      their colorimetric detection properties.

PMID- 29072771
TI  - A ROS-responsive polymeric micelle with a pi-conjugated thioketal moiety for
      enhanced drug loading and efficient drug delivery.
AB  - As the implications of reactive oxygen species (ROS) are elucidated in many
      diseases, ROS-responsive nanoparticles are attracting great interest from
      researchers. In this work, a ROS sensitive thioketal (TK) moiety with a pi
      conjugated structure was introduced into biodegradable methoxy poly(ethylene
      glycol)-thioketal-poly(epsilon-caprolactone)mPEG-TK-PCL micelles as a linker,
      which was designed to speed up the drug release and thus enhance the therapeutic
      efficacy. The micelle showed a high drug loading content of 12.8% and excellent
      stability under physiological conditions because of the evocation of pi-pi
      stacking and hydrophobic interactions with the anticancer drug doxorubicin (DOX).
      The polymeric micelle presented a better drug carrier capacity and higher in
      vitro anticancer efficacy towards cancer cells. The in vivo study showed that DOX
      loaded mPEG-TK-PCL micelles displayed lower toxicity towards normal cells and
      remarkably enhanced antitumor efficacy. This research provides a way to design
      potential drug carriers for efficient cancer chemotherapy.

PMID- 29072772
TI  - Long-term patient-reported outcomes from an open-label safety and efficacy study
      of bosutinib in Philadelphia chromosome-positive chronic myeloid leukemia
      patients resistant or intolerant to prior therapy.
AB  - BACKGROUND: Health-related quality of life (HRQOL) in patients with chronic-phase
      chronic myeloid leukemia (CML) is important because of the requirement for long
      term treatment. This study assessed HRQOL in bosutinib-treated patients with
      Philadelphia chromosome-positive CML and resistance or intolerance to 1 (chronic
      phase second-line [CP2L]) or more (chronic-phase third-line [CP3L]) tyrosine
      kinase inhibitors who had 264 weeks or more of follow-up (ClinicalTrials.gov
      identifier NCT00261846). METHODS: Patient-reported HRQOL was assessed with the
      EuroQol 5-Dimensions Questionnaire (EQ-5D) and the Functional Assessment of
      Cancer Therapy-Leukemia (FACT-Leu). RESULTS: In total, 284 and 119 patients
      composed the CP2L and CP3L cohorts, respectively. At treatment completion, more
      than 50% of the patients in the CP2L and CP3L cohorts completed the EQ-5D and
      FACT-Leu assessments. The EQ-5D and EQ-5D visual analog scale scores were stable
      in both cohorts throughout treatment. The mean FACT-Leu scores were generally
      stable over time but were lower in magnitude in the CP3L cohort versus the CP2L
      cohort. The FACT-Leu scale scores of a subset of patients with chronic diarrhea
      (CP2L, n = 101; CP3L, n = 30) were similar to the scores of the larger cohorts.
      Minimally important differences (MIDs) from baseline for the FACT-Leu scale
      scores were observed for the following: emotional well-being (EWB), Functional
      Assessment of Cancer Therapy-General (FACT-G) Total, FACT-Leu Total, and
      Functional Assessment of Cancer Therapy Trial Outcome Index (FACT-TOI) in the
      CP2L cohort and FACT-Leu Total in the CP3L cohort. Among patients with chronic
      diarrhea, MIDs were observed for EWB, FACT-G Total, FACT-Leu Total, and FACT-TOI
      in the CP2L cohort and for EWB, FACT-G Total, and FACT-Leu Total in the CP3L
      cohort. CONCLUSIONS: HRQOL was maintained with long-term bosutinib treatment for
      patients with CP2L and CP3L CML. Cancer 2018;124:587-95. (c) 2017 The Authors.
      Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
      This is an open access article under the terms of the Creative Commons
      Attribution-NonCommercial License, which permits use, distribution and
      reproduction in any medium, provided the original work is properly cited and is
      not used for commercial purposes.

PMID- 29072773
TI  - Effect of hospital safety net designation on treatment use and survival in
      hepatocellular carcinoma.
AB  - BACKGROUND: Racial/ethnic minorities with hepatocellular carcinoma (HCC) have
      worse survival than non-Hispanic whites. Comparing patient outcomes across health
      care delivery systems can identify biological and care delivery mechanisms
      contributing to this disparity. We compared presentation, treatment, and survival
      of HCC patients treated at safety net hospitals (SNHs) and non-SNHs. METHODS:
      Patients diagnosed with HCC from 2001 to 2012 were identified in the Texas Cancer
      Registry. We compared hospital and patient characteristics across three hospital
      categories: non-SNHs, low-proportion SNHs (l-SNHs), and high-proportion SNHs (h
      SNHs). Covariate-adjusted treatment use and overall survival were compared among
      the 3 hospital categories. RESULTS: Despite comprising only 23% of hospitals, h
      SNHs cared for 42% of 17,489 HCC patients and disproportionately delivered care
      to racial/ethnic minorities and patients of low socioeconomic status compared
      with non-SNHs. Compared with non-SNHs, treatment use was similar at l-SNHs (45%
      vs 45%; adjusted odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06)
      but significantly lower at h-SNHs (32% vs 45%; OR, 0.64; 95% CI, 0.57-0.73).
      Similarly, patients with localized HCC were less likely to undergo curative
      treatment at h-SNHs than non-SNHs (OR, 0.51; 95% CI, 0.40-0.66). Compared with
      non-SNHs, overall survival was similar at l-SNHs (hazard ratio [HR], 0.93; 95%
      CI, 0.89-0.98) but significantly worse at h-SNHs (HR, 1.30; 95% CI, 1.22-1.39).
      CONCLUSION: Patients at SNHs are less likely to undergo HCC treatment, even when
      diagnosed at an early stage, which likely contributes to worse survival. System
      level differences in care delivery may partly explain racial/ethnic and
      socioeconomic disparities in HCC prognosis. Cancer 2018;124:743-51. (c) 2017
      American Cancer Society.

PMID- 29072774
TI  - Human papillomavirus and World Health Organization type III nasopharyngeal
      carcinoma: Multicenter study from an endemic area in Southern China.
AB  - BACKGROUND: The current study was conducted to study the incidence of human
      papillomavirus (HPV)-associated nasopharyngeal carcinoma (NPC) in Southern China
      and the corresponding treatment outcome. METHODS: A retrospective chart review
      with a level of evidence of 4 was performed. RESULTS: Between 2000 and 2015, a
      total of 1328 patients with NPC were treated in 3 study institutes in Hong Kong
      and Foshan City in Guangdong Province, China. All tumors were undifferentiated,
      nonkeratinizing carcinoma, of which 91.9% were positive for the Epstein-Barr
      virus (EBV+) and 7.7% were positive for HPV/p16 (HPV+). Although coinfection with
      both viruses occurred only in 8 patients (0.6%), 94 patients had tumors that were
      EBV negative (EBV-) and HPV+. All patients were treated with intensity-modulated
      radiotherapy alone for American Joint Committee on Cancer stage I and II disease,
      and concurrent chemoradiotherapy for stage III and IV disease. With a median
      follow-up of 72.8 months, the authors found that the local recurrence rate was
      significantly lower for patients with tumors that were EBV-/HPV+ compared with
      patients with tumors that were EBV+/HPV- (6.4% vs 13.8%; P = .03). Similar trends
      were observed for the 5-year disease-free survival rate (89.8% vs 70.8%; P =.03)
      and 5-year overall survival rate (86% vs 72%; P =.03). CONCLUSIONS: In regions
      that are endemic for NPC, the prevalence of EBV and HPV coinfection in patients
      with NPC is extremely low. Conversely, patients with EBV-/HPV+ NPC demonstrate
      significantly better local tumor control and survival after radiotherapy. Cancer
      2018;124:530-6. (c) 2017 American Cancer Society.

PMID- 29072775
TI  - A new endoscopic minimal invasive approach for pudendal nerve and inferior
      cluneal nerve neurolysis: An anatomical study.
AB  - AIM: To describe a new minimal invasive approach of the gluteal region which will
      permit to perform neurolysis of the pudendal and cluneal nerves in case of
      perineal neuralgia due to an entrapment of these nerve trunks. METHOD: Ten
      transgluteal approaches were performed on five cadavers. Relevant anatomic
      structures were dissected and further described. Neurolysis of the pudendal nerve
      or cluneal nerves were performed. Landmarks for secure intraoperative navigation
      were indicated. RESULTS: The first operative trocar for the camera was inserted
      with regards to the iliac crest in the deep gluteal space. With the aid of
      pneumodissection, the infragluteal plane was dissected. The piriformis muscle was
      identified as well as the sciatic and the posterior femoral cutaneous nerve.
      Consequently, the sciatic tuberosity was visualized together with the cluneal
      nerves. Hereafter, the second trocar was introduced caudal to the first one and
      placed on an horizontal line passing at the level of the coccyx, allowing access
      to the ischial spine and the visualization of the pudendal nerve and vessels. A
      third 5 mm trocar was then inserted medial from the first one, permitting to
      dissect and transsect the sacrospinous ligament. The pudendal nerve was
      subsequently transposed and followed on its course in the pudendal channel.
      CONCLUSIONS: A reliable exploration of the gluteal region including
      identification of the sciatic, pudendal, and posterior femoral cutaneous nerves
      is feasible using a minimal invasive transgluteal procedure. Consequently, the
      transposition of the pudendal nerve and the liberation of the cluneal nerves can
      be performed.

PMID- 29072777
TI  - MS2 and Qbeta bacteriophages reveal the contribution of surface hydrophobicity on
      the mobility of non-enveloped icosahedral viruses in SDS-based capillary zone
      electrophoresis.
AB  - SDS is commonly employed as BGE additive in CZE analysis of non-enveloped
      icosahedral viruses. But the way by which SDS interacts with the surface of such
      viruses remains to date poorly known, making complicate to understand their
      behavior during a run. In this article, two related bacteriophages, MS2 and
      Qbeta, are used as model to investigate the migration mechanism of non-enveloped
      icosahedral viruses in SDS-based CZE. Both phages are characterized by similar
      size and surface charge but significantly different surface hydrophobicity (Qbeta
      > MS2, where '>' means 'more hydrophobic than'). By comparing their
      electrophoretic mobility in the presence or not of SDS on both sides of the CMC,
      we show that surface hydrophobicity of phages is a key factor influencing their
      mobility and that SDS-virus association is driven by hydrophobic interactions at
      the surface of virions. The CZE analyses of heated MS2 particles, which over
      express hydrophobic domains at their surface, confirm this finding. The
      correlations between the present results and others from the literature suggest
      that the proposed mechanism might not be exclusive to the bacteriophages examined
      here.

PMID- 29072776
TI  - Antipsychotic plasma levels in the assessment of poor treatment response in
      schizophrenia.
AB  - OBJECTIVE: Treatment resistance is a challenge for the management of
      schizophrenia. It is not always clear whether inadequate response is secondary to
      medication ineffectiveness, as opposed to medication underexposure due to non
      adherence or pharmacokinetic factors. We investigated the prevalence of
      subtherapeutic antipsychotic plasma levels in patients identified as treatment
      resistant by their treating clinician. METHOD: Between January 2012 and April
      2017, antipsychotic plasma levels were measured in 99 individuals provisionally
      diagnosed with treatment-resistant schizophrenia by their treating clinicians,
      but not prescribed clozapine. Patients were followed up to determine whether they
      were subsequently admitted to hospital. RESULTS: Thirty-five per cent of plasma
      levels were subtherapeutic, and of these, 34% were undetectable. Black ethnicity
      (P = 0.006) and lower dose (P < 0.001) were significantly associated with
      subtherapeutic/undetectable plasma levels. Individuals with
      subtherapeutic/undetectable levels were significantly more likely to be admitted
      to hospital (P = 0.02). CONCLUSION: A significant proportion of patients
      considered treatment-resistant have subtherapeutic antipsychotic plasma levels,
      and this is associated with subsequent admission. The presence of subtherapeutic
      plasma levels may suggest a need to address adherence or pharmacokinetic factors
      as opposed to commencing clozapine treatment. While antipsychotic levels are not
      recommended for the routine adjustment of dosing, they may assist with the
      assessment of potential treatment resistance in schizophrenia.

PMID- 29072778
TI  - Regulation of Kisspeptin Synthesis and Release in the Preoptic/Anterior
      Hypothalamic Region of Prepubertal Female Rats: Actions of IGF-1 and Alcohol.
AB  - BACKGROUND: Alcohol (ALC) causes suppressed secretion of prepubertal luteinizing
      hormone-releasing hormone (LHRH). Insulin-like growth factor-1 (IGF-1) and
      kisspeptin (Kp) are major regulators of LHRH and are critical for puberty. IGF-1
      may be an upstream mediator of Kp in the preoptic area and rostral hypothalamic
      area (POA/RHA) of the rat brain, a region containing both Kp and LHRH neurons. We
      investigated the ability of IGF-1 to stimulate prepubertal Kp synthesis and
      release in POA/RHA, and the potential inhibitory effects of ALC. METHODS:
      Immature female rats were administered either ALC (3 g/kg) or water via gastric
      gavage at 0730 hours. At 0900 hours, both groups were subdivided where half
      received either saline or IGF-1 into the brain third ventricle. A second dose of
      ALC (2 g/kg) or water was administered at 1130 hours. Rats were killed 6 hours
      after injection and POA/RHA region collected. RESULTS: IGF-1 stimulated Kp, an
      action blocked by ALC. Upstream to Kp, IGF-1 receptor (IGF-1R) activation, as
      demonstrated by the increase in insulin receptor substrate 1, resulted in
      activation of Akt, tuberous sclerosis 2, ras homologue enriched in brain, and
      mammalian target of rapamycin (mTOR). ALC blocked the central action of IGF-1 to
      induce their respective phosphorylation. IGF-1 specificity and ALC specificity
      for the Akt-activated mTOR pathway were demonstrated by the absence of effects on
      PRAS40. Furthermore, IGF-1 stimulated Kp release from POA/RHA incubated in vitro.
      CONCLUSIONS: IGF-1 stimulates prepubertal Kp synthesis and release following
      activation of a mTOR signaling pathway, and ALC blocks this pathway at the level
      of IGF-1R.

PMID- 29072779
TI  - Effects of Posidonia oceanica banquettes on intake, digestibility, nitrogen
      balance and metabolic profiles in sheep.
AB  - BACKGROUND: The marine plant Posidonia oceanica (L.) (PO) has been demonstrated
      in goats to be a source of fibre. The aim of the present study was to assess the
      effects of introducing this marine plant as a substitute for barley straw in the
      feed of mature ewes, assessing the effects of its addition on intake,
      digestibility and ruminal fermentation and on the ewes' metabolic profiles
      (energy and protein). PO was used at 75 g day-1 per ewe (15% of the total
      forage), 150 g day-1 per ewe (30% of the total forage) and 300 g day-1 per ewe
      (60% of the total forage). RESULTS: Substitution of 15% of the forage with PO has
      no negative consequences on dry matter intake, final live weight and metabolic
      status in mature ewes; in addition, PO may improve the animal's nitrogen
      utilisation. The upper limit of substitution was 30%, where only few changes were
      noted without metabolic consequences. Substitution of 60% impaired performance
      and affects tissue functions in the animal's body. CONCLUSION: Moderate
      quantities of barley straw (between 75 and 150 g day-1 per ewe) can be replaced
      by PO in feed rations for mature ewes. (c) 2017 Society of Chemical Industry.

PMID- 29072782
TI  - The ethically challenging trade of forced surrogacy in Nepal.

PMID- 29072781
TI  - Diagnostic and genetic overlap of three common mental disorders in structured
      interviews and health registries.
AB  - OBJECTIVE: To investigate whether diagnostic data from structured interviews,
      primary care and specialist care registries on major depressive disorder (MDD),
      anxiety disorders (AD) and alcohol use disorder (AUD) identify the same
      individuals, yield comparable comorbidity estimates and reflect the same genetic
      influences. METHODS: Registry data from primary and specialist care were
      available for 11 727 twins and diagnostic interview data for 2271 of these. We
      used logistic regression analyses and biometric modelling to investigate the
      overlap between the data sources. RESULTS: Most individuals meeting diagnostic
      criteria at interview were not registered with a corresponding diagnosis. The
      rates of registration were higher for MDD (36% in primary care and 15% in
      specialist care) and AD (21% and 18%) than for AUD (3% and 7%). Comorbidity
      estimated as odds ratios, but not as polychoric correlations, was higher in the
      registries than in the interviews. Genetic influences on the disorders were
      highly correlated across data sources (median r = 0.81), bordering unity for MDD
      and AD. CONCLUSION: Prevalence and comorbidity estimates differ between
      registries and population-based assessment. Nevertheless, diagnoses from health
      registries reflect the same genetic influences as common mental disorders
      assessed in the general population, indicating generalizability of aetiological
      factors across data sources.

PMID- 29072780
TI  - Axonal GABAA receptors depolarize presynaptic terminals and facilitate
      transmitter release in cerebellar Purkinje cells.
AB  - KEY POINTS: GABAA receptors have been described in the axonal compartment of
      neurons; contrary to dendritic GABAA receptors, axonal GABAA receptors usually
      induce depolarizing responses. In this study we describe the presence of
      functional axonal GABAA receptors in cerebellar Purkinje cells by using a
      combination of direct patch-clamp recordings from the axon terminals and laser
      GABA photolysis. In Purkinje cells, axonal GABAA receptors are depolarizing and
      induce an increase in neurotransmitter release that results in a change of short
      term synaptic plasticity. These results contribute to our understanding of the
      cellular mechanisms of action of axonal GABAA receptors and highlight the
      importance of the presynaptic compartment in neuronal computation. ABSTRACT: In
      neurons of the adult brain, somatodendritic GABAA receptors (GABAA Rs) mediate
      fast synaptic inhibition and play a crucial role in synaptic integration. GABAA
      Rs are not only present in the somatodendritic compartment, but also in the
      axonal compartment where they modulate action potential (AP) propagation and
      transmitter release. Although presynaptic GABAA Rs have been reported in various
      brain regions, their mechanisms of action and physiological roles remain obscure,
      particularly at GABAergic boutons. Here, using a combination of direct whole
      bouton or perforated patch-clamp recordings and local GABA photolysis in single
      axonal varicosities of cerebellar Purkinje cells, we investigate the subcellular
      localization and functional role of axonal GABAA Rs both in primary cultures and
      acute slices. Our results indicate that presynaptic terminals of PCs carry GABAA
      Rs that behave as auto-receptors; their activation leads to a depolarization of
      the terminal membrane after an AP due to the relatively high cytoplasmic Cl-
      concentration in the axon, but they do not modulate the AP itself. Paired
      recordings from different terminals of the same axon show that the GABAA R
      mediated local depolarizations propagate substantially to neighbouring
      varicosities. Finally, the depolarization mediated by presynaptic GABAA R
      activation augmented Ca2+ influx and transmitter release, resulting in a marked
      effect on short-term plasticity. Altogether, our results reveal a mechanism by
      which presynaptic GABAA Rs influence neuronal computation.

PMID- 29072783
TI  - Living Alone and Discharge to Skilled Nursing Facility Care after Hospitalization
      in Older Adults.
AB  - BACKGROUND/OBJECTIVES: Community-based older adults are increasingly living
      alone. When they become ill, they might need greater support from the healthcare
      system than would those who live with others. There also has been a growing
      concern about the high use of postacute care such as skilled nursing facility
      (SNF) care and the level of variation in this use between hospitals and regions.
      Our objective was to examine whether living alone contributed to the risk of
      being discharged to a SNF. DESIGN: Retrospective cohort study. SETTING:
      Massachusetts General Hospital. PARTICIPANTS: Community-dwelling individuals aged
      50 and older admitted to the medical service and discharged alive between July
      2014 and August 2015 (N = 7,029). MEASUREMENTS: We extracted demographic,
      clinical, and functional data from the electronic medical record and used
      multivariable logistic regression to determine whether living alone at the time
      of hospitalization was associated with subsequent discharge to a SNF. RESULTS: Of
      eligible individuals, 24.8% reported living alone before admission. Those living
      alone were more likely to be female, older, and more independent before admission
      than those living with others. Of all participants, 10.9% were discharged to a
      SNF. After adjustment, participants living alone had more than twice the odds of
      being discharged to a SNF (odds ratio = 2.23, 95% confidence interval = 1.85
      2.69, P < .001). DISCUSSION: People living alone are more likely to be discharged
      to SNFs, even when compared to other individuals with similar levels of clinical
      complexity and functional status. To the extent that this variation is due to a
      lack of home support, it could be possible to reduce SNF use through additional
      home services after hospital discharge.

PMID- 29072784
TI  - Addition of urea and thiourea to electrophoresis sample buffer improves
      efficiency of protein extraction from TCA/acetone-treated smooth muscle tissues
      for phos-tag SDS-PAGE.
AB  - Phosphorylation analysis by using phos-tag technique has been reported to be
      suitable for highly sensitive quantification of smooth muscle myosin regulatory
      light chain (LC20 ) phosphorylation. However, there is another factor that will
      affect the sensitivity of phosphorylation analysis, that is, protein extraction.
      Here, we optimized the conditions for total protein extraction out of
      trichloroacetic acid (TCA)-fixed tissues. Standard SDS sample buffer extracted
      less LC20 , actin and myosin phosphatase targeting subunit 1 (MYPT1) from
      TCA/acetone treated ciliary muscle strips. On the other hand, sample buffer
      containing urea and thiourea in addition to lithium dodecyl sulfate (LDS) or SDS
      extracted those proteins more efficiently, and thus increased the detection
      sensitivity up to 4-5 fold. Phos-tag SDS-PAGE separated dephosphorylated and
      phosphorylated LC20 s extracted in LDS/urea/thiourea sample buffer to the same
      extent as those in standard SDS buffer. We have concluded that LDS (or SDS)
      /urea/thiourea sample buffer is suitable for highly sensitive phosphorylation
      analysis in smooth muscle, especially when it is treated with TCA/acetone.

PMID- 29072785
TI  - Predicting CYP3A-mediated midazolam metabolism in critically ill neonates,
      infants, children and adults with inflammation and organ failure.
AB  - AIMS: Inflammation and organ failure have been reported to have an impact on
      cytochrome P450 (CYP) 3A-mediated clearance of midazolam in critically ill
      children. Our aim was to evaluate a previously developed population
      pharmacokinetic model both in critically ill children and other populations, in
      order to allow the model to be used to guide dosing in clinical practice.
      METHODS: The model was evaluated externally in 136 individuals, including
      (pre)term neonates, infants, children and adults (body weight 0.77-90 kg, C
      reactive protein level 0.1-341 mg l-1 and 0-4 failing organs) using graphical and
      numerical diagnostics. RESULTS: The pharmacokinetic model predicted midazolam
      clearance and plasma concentrations without bias in postoperative or critically
      ill paediatric patients and term neonates [median prediction error (MPE) <30%].
      Using the model for extrapolation resulted in well-predicted clearance values in
      critically ill and healthy adults (MPE <30%), while clearance in preterm neonates
      was over predicted (MPE >180%). CONCLUSION: The recently published
      pharmacokinetic model for midazolam, quantifying the influence of maturation,
      inflammation and organ failure in children, yields unbiased clearance predictions
      and can therefore be used for dosing instructions in term neonates, children and
      adults with varying levels of critical illness, including healthy adults, but not
      for extrapolation to preterm neonates.

PMID- 29072786
TI  - Effects of micronized and nano-copper azole on marine benthic communities.
AB  - The widespread use of copper nanomaterials (CuNMs) as antibacterial and
      antifouling agents in consumer products increases the risk for metal
      contamination and adverse effects in aquatic environments. Information gaps exist
      on the potential toxicity of CuNMs in marine environments. We exposed field
      collected marine meio- and macrobenthic communities to sediments spiked with
      micronized copper azole (MCA) using a novel method that brings intact benthic
      cores into the laboratory and exposes the organisms via surface application of
      sediments. Treatments included field and laboratory controls, 3 spiked sediments:
      low-MCA (51.9 mg/kg sediment), high-MCA (519 mg/kg sediment), and CuSO4 (519
      mg/kg sediment). In addition, single-species acute testing was performed with
      both MCA and CuSO4. Our results indicate that meio- and macrofaunal assemblages
      exposed to High-MCA and CuSO4 treatments differed significantly from both the
      laboratory control and the low-MCA treatments. Differences in macrofauna were
      driven by decreases in 3 Podocopa ostracod species, the bivalve Gemma gemma, and
      the polychaetes Exogone verugera and Prionospio heterobranchia relative to the
      laboratory control. Differences in the meiofaunal community are largely driven by
      nematodes. The benthic community test results were more sensitive than the single
      species test results. Findings of this investigation indicate that CuNMs
      represent a source of risk to marine benthic communities comparable to that of
      dissolved Cu. Environ Toxicol Chem 2018;37:362-375. Published 2017 Wiley
      Periodicals Inc. on behalf of SETAC. This article is a US government work and, as
      such, is in the public domain in the United States of America.

PMID- 29072787
TI  - PROMIS measures can be used to assess symptoms and function in long-term
      hematopoietic cell transplantation survivors.
AB  - BACKGROUND: Patient-reported outcomes for hematopoietic cell transplantation
      (HCT) survivors are well characterized with established measures; however, there
      is little experience with the new, freely available Patient-Reported Outcomes
      Measurement Information System (PROMIS) measures in this population. The aim of
      this study was to compare the performance of the PROMIS measures in the HCT
      setting with the performance of the commonly used 36-Item Short Form Health
      Survey (SF-36). METHODS: Adult HCT survivors from the Fred Hutchinson Cancer
      Research Center (n = 4446) were mailed a survey that included the following as
      part of an annual follow-up survey: the Patient-Reported Outcomes Measurement
      Information System-Global Health (PROMIS-GH; 10 questions), the 29-Item Patient
      Reported Outcomes Measurement Information System Profile (PROMIS-29), and the SF
      36. RESULTS: Both the SF-36 and PROMIS measures were available for 1634 HCT
      recipients (503 autologous recipients and 1131 allogeneic recipients). The
      overall response rate was 46%. The median time after transplantation for
      allogeneic and autologous recipients was 12.0 years (range, 0.4-44.1 years) and
      6.1 years (range, 0.4-30.1 years), respectively. With the SF-36 or PROMIS-GH,
      overall physical functioning was somewhat lower in comparison with the general
      population, but mental functioning was similar. Component and domain scores with
      similar contents were strongly correlated by Pearson correlation coefficients:
      the Global Health-Physical and SF-36 Physical Component Summary scores for
      autologous (r = 0.82) and allogeneic recipients (r = 0.83) and the PROMIS-29 and
      SF-36 physical function, pain, and vitality/fatigue scores for allogeneic (0.87, 
      0.82, and -0.82, respectively) and autologous recipients (0.84, -0.82, and -0.81,
      respectively). The correlation between the Global Health-Mental and SF-36 Mental
      Component Summary scores was lower (0.70 for autologous recipients and 0.72 for
      allogeneic recipients). CONCLUSIONS: Physical and mental symptoms and function in
      autologous and allogeneic HCT survivors can be adequately assessed with PROMIS-29
      and PROMIS-GH. Cancer 2018;124:841-9. (c) 2017 American Cancer Society.

PMID- 29072788
TI  - Uncovering the structure of agreeableness from self-report measures.
AB  - OBJECTIVE: Although there are several models of the lower-order structure of
      Agreeableness, empirically derived descriptions of this domain are largely
      nonexistent. We examined the factor structure of Agreeableness items from
      multiple scales in order to empirically determine the facet-level structure of
      the domain. METHOD: Participants (N = 1,205; 73% female; 84% White; Mage  = 35.5,
      SD = 17.26) completed 131 items from 22 scales measuring Agreeableness. RESULTS:
      A series of factor analyses was conducted on 104 items to identify factor
      emergence of the domain from a single factor to increasingly more specific
      factors. A five-factor solution consisting of facets labeled Compassion,
      Morality, Trust, Affability, and Modesty was identified as most appropriate.
      Factors from all levels of the construct were compared to current measures of the
      domain as well as a number of criterion variables. The patterns of association
      with criterion variables at the lower level of the Agreeableness domain showed
      significant divergence. CONCLUSIONS: The current results highlight how specific
      Agreeableness traits unfold from broader to more specific facets and how these
      traits are represented in existing measures of this important domain.

PMID- 29072789
TI  - Abnormally invasive placentation in a woman with congenital myotonic dystrophy.

PMID- 29072791
TI  - Improving the accrual of racial and ethnic minority patients in clinical trials:
      Time to raise the stakes.

PMID- 29072790
TI  - Sleep disturbance in men receiving androgen deprivation therapy for prostate
      cancer: The role of hot flashes and nocturia.
AB  - BACKGROUND: Patients with prostate cancer receiving androgen deprivation therapy
      (ADT) are at risk of sleep disturbance; however, to the authors' knowledge, the
      mechanisms by which ADT may affect sleep are not well understood. The current
      study compared objective and subjective sleep disturbance in ADT recipients and
      controls and examined whether sleep disturbance in ADT recipients is attributable
      to the influence of ADT on hot flashes and nocturia. METHODS: Patients with
      prostate cancer were assessed before or within 1 month after the initiation of
      ADT as well as 6 months and 12 months later (78 patients). Patients with prostate
      cancer were treated with prostatectomy only (99 patients) and men with no history
      of cancer (108 men) were assessed at similar intervals. Participants self
      reported their sleep disturbance (Insomnia Severity Index) and interference from
      hot flashes (Hot Flash Related Daily Interference Scale). One hundred
      participants also wore actigraphs for 3 days at the 6-month assessment to measure
      objective sleep disturbance and reported their nocturia frequency. RESULTS: ADT
      recipients reported worse sleep disturbance, higher rates of clinically
      significant sleep disturbance, and greater hot flash interference than controls
      (Ps<=.03). In cross-sectional analyses among those with actigraphy data, ADT
      recipients had greater objective sleep disturbance and more episodes of nocturia
      (Ps<.01). Cross-sectional mediation analyses demonstrated that the association
      between ADT and objectively and subjectively measured sleep disturbance was
      partly attributable to nocturia and hot flashes (Ps<.05). CONCLUSIONS: The
      results of the current study suggest that the association between ADT and sleep
      may be partly explained by nocturia and hot flash interference. Future studies
      should examine behavioral and pharmacologic interventions to address these
      symptoms among ADT recipients. Cancer 2018;124:499-506. (c) 2017 American Cancer
      Society.

PMID- 29072792
TI  - Oxidation pretreatment by calcium hypochlorite to improve the sensitivity of
      enzyme inhibition-based detection of organophosphorus pesticides.
AB  - BACKGROUND: Enzyme inhibition-based detection is the most widely used method for
      rapid detection of organophosphorus pesticides (OPs) in food and agricultural
      products. However, the accuracy of the method is negatively affected by low
      inhibitory activities of OPs with P?S moiety on acetylcholinesterase. RESULTS: We
      demonstrated that oxidation pretreatments with bromine, hydrogen peroxide, or
      calcium hypochlorite significantly enhanced the enzyme inhibitory activities of
      these OPs. Especially, calcium hypochlorite (0.05%) pretreatment converted the
      P?S moiety in OPs to P?O and produced the most potent and steady inhibitory
      effect on the enzyme. This, in turn, resulted in a dramatic increase in the
      sensitivity of enzyme inhibition-based detection of these OPs by as much as 2 to
      7 orders of magnitude. Importantly, this enhanced detection of OPs was validated
      in various vegetable samples. CONCLUSION: Our findings provide a solid basis to
      use calcium hypochlorite pretreatment for the improved detection of OPs by the
      enzyme inhibition-based method. (c) 2017 Society of Chemical Industry.

PMID- 29072794
TI  - Effects of GABA active steroids in the female brain with a focus on the
      premenstrual dysphoric disorder.
AB  - Premenstrual dysphoric disorder (PMDD) afflicts 3%-5% of women of childbearing
      age, and is characterised by recurrent negative mood symptoms (eg, irritability,
      depression, anxiety and emotional lability) during the luteal phase of the
      menstrual cycle. The aetiology of PMDD is unknown, although a temporal
      association with circulating ovarian steroids, in particular progesterone and its
      metabolite allopregnanolone, has been established during the luteal phase.
      Allopregnanolone is a positive modulator of the GABAA receptor: it is sedative in
      high concentrations but may precipitate paradoxical adverse effects on mood at
      levels corresponding to luteal phase concentrations in susceptible women.
      Saccadic eye velocity (SEV) is a measure of GABAA receptor sensitivity; in
      experimental studies of healthy women, i.v. allopregnanolone decreases SEV. Women
      with PMDD display an altered sensitivity to an i.v. injection of allopregnanolone
      compared to healthy controls in this model. In functional magnetic resonance
      imaging (fMRI) studies, women with PMDD react differently to emotional stimuli in
      contrast to controls. A consistent finding in PMDD patients is increased amygdala
      reactivity during the luteal phase. Post-mortem studies in humans have revealed
      that allopregnanolone concentrations vary across different brain regions,
      although mean levels in the brain also reflect variations in peripheral serum
      concentrations. The amygdala processes emotions such as anxiety and aggression.
      This is interesting because allopregnanolone is detected at high concentrations
      within the region into which marked increases in blood flow are measured with
      fMRI following progesterone/allopregnanolone administration. Allopregnanolone
      effects are antagonised by its isomer isoallopregnanolone (UC1010), which
      significantly reduces negative mood symptoms in women with PMDD when administered
      s.c. in the premenstrual phase. This was shown in a randomised, placebo
      controlled clinical trial in which the primary outcome was change in symptom
      scoring on the Daily Rating of Severity of Problems (DRSP): the treatment reduced
      negative mood scores (P < .005), as well as total DRSP scores (P < .01), compared
      to placebo in women with PMDD. In conclusion, the underlying studies of this
      review provide evidence that allopregnanolone is the provoking factor behind the
      negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the
      symptoms as a result of its ability to antagonise the allopregnanolone effect on
      the GABAA receptor.

PMID- 29072793
TI  - Cytoarchitectonically-driven MRI atlas of nonhuman primate hippocampus:
      Preservation of subfield volumes in aging.
AB  - Identification of primate hippocampal subfields in vivo using structural MRI
      imaging relies on variable anatomical guidelines, signal intensity differences,
      and heuristics to differentiate between regions (Yushkevich et al., ). Thus, a
      clear anatomically-driven basis for subfield demarcation is lacking. Recent work,
      however, has begun to develop methods to use ex vivo histology or ex vivo MRI
      (Adler et al., 2014; Iglesias et al., 2015) that have the potential to inform
      subfield demarcations of in vivo images. For optimal results, however, ex vivo
      and in vivo images should ideally be matched within the same healthy brains, with
      the goal to develop a neuroanatomically-driven basis for in vivo structural MRI
      images. Here, we address this issue in young and aging rhesus macaques (young n =
      5 and old n = 5) using ex vivo Nissl-stained sections in which we identified the
      dentate gyrus, CA3, CA2, CA1, subiculum, presubiculum, and parasubiculum guided
      by morphological cell properties (30 MUm thick sections spaced at 240 MUm
      intervals and imaged at 161 nm/pixel). The histologically identified boundaries
      were merged with in vivo structural MRIs (0.625 * 0.625 * 1 mm) from the same
      subjects via iterative rigid and diffeomorphic registration resulting in
      probabilistic atlases of young and old rhesus macaques. Our results indicate
      stability in hippocampal subfield volumes over an age range of 13 to 32 years,
      consistent with previous results showing preserved whole hippocampal volume in
      aged macaques (Shamy et al., 2006). Together, our methods provide a novel
      approach for identifying hippocampal subfields in non-human primates and a
      potential 'ground truth' for more accurate identification of hippocampal subfield
      boundaries on in vivo MRIs. This could, in turn, have applications in humans
      where accurately identifying hippocampal subfields in vivo is a critical research
      goal.

PMID- 29072795
TI  - Preparation of Pillar[5]arene-Based [2]Rotaxanes by a Stopper-Exchange Strategy.
AB  - A pillar[5]arene-containing rotaxane building block bearing exchangeable stoppers
      has been prepared in multigram scale quantities with high yields from the
      reaction of 2,4-dinitrophenol (DNP) with the inclusion complex resulting from the
      association of dodecanedioyl chloride with 1,4-diethoxypillar[5]arene. Stopper
      exchange reactions have been achieved by treatment of the resulting DNP diester
      with various amines through an addition-elimination mechanism preventing the
      unthreading of the axle component during the reaction and thus preserving the
      [2]rotaxane structures. The resulting diamide [2]rotaxane derivatives have thus
      been obtained in good to excellent yields. Importantly, [2]rotaxanes difficult or
      impossible to prepare by direct introduction of the two stoppers in a single
      synthetic step are now easily available.

PMID- 29072796
TI  - Atrial tachycardias: Cause or effect with ablation of persistent atrial
      fibrillation?
AB  - INTRODUCTION: It is largely believed that atrial tachycardias (ATs) encountered
      during ablation of persistent atrial fibrillation (PsAF) are a byproduct of
      ablative lesions. We aimed to explore the alternative hypothesis that they may be
      a priori drivers of AF remaining masked until other AF sources are reduced or
      eliminated. METHODS AND RESULTS: Radiofrequency ablation of fibrillatory drivers
      mapped by electrocardiographic imaging (ECGI; ECVUETM, Cardioinsight
      Technologies, Cleveland, OH, USA) terminated PsAF in 198 (73%) out of 270
      patients (61 +/- 10 years, 9 +/- 9 m). Two hundred and six ATs in 158 patients
      were subsequently mapped. Their anatomic relationship to the fibrillatory drivers
      prospectively identified by ECGI was then established. There were 26 (13%), 52
      (25%), and 128 (62%) focal, localized, and macrore-entrant ATs, respectively. In
      focal/localized re-entrant ATs, 64 (82%) were terminated within an AF-driver
      region, in which 26 (81%) among 32 focal/localized ATs analyzed with 3-D-mapping
      system merged to driver map occurred from AF-driver regions in 1.0 +/- 1.0 cm
      distance from the driver core. Importantly, there was no attempt at ablation of
      the associated AF-driver region in 25 of 64 (39%) of focal/localized re-entrant
      ATs. The sites of ATs origin generally had low-voltage, fractionated, and long
      duration electrograms in AF. All but two focal/localized re-entrant ATs were
      successfully ablated. CONCLUSION: The majority of post-AF-ablation focal and
      localized re-entrant ATs originate from the region of prospectively established
      AF-driver regions. A third of these are localized to regions not subsequently
      submitted to ablation. These data suggest that many ATs exist, although not
      necessarily manifest independently, prior to ablation. They may have a role in
      the maintenance of PsAF in these individuals.

PMID- 29072797
TI  - A Versatile Synthesis of Pentacosafuranoside Subunit Reminiscent of Mycobacterial
      Arabinogalactan Employing One Strategic Glycosidation Protocol.
AB  - Oligosaccharides are involved in a myriad of biological phenomena. Many
      glycobiological experiments can be undertaken if homogenous and well-defined
      oligosaccharides are accessible. Mycobacterial cell walls contain arabinogalactan
      as one of the major constituents that is challenging for chemical synthesis.
      Therefore, the major aim of this investigation is to synthesise a major
      oligosaccharide portion of the arabinogalactan. The pentacosafuranoside (25mer)
      synthesis involved installation of several arabinofuranosidic linkages through
      neighbouring group participation for 1,2-trans linkages and oxidation-reduction
      strategy for the 1,2-cis Araf. A strategically placed n-pentenyl moiety at the
      reducing end enables ligation of biomolecular probes through celebrated cross
      metathesis or thiol-ene click reactions. Several linear and branched
      oligosaccharides were synthesised ranging from trisaccharide to
      pentadecasaccharide during this endeavour. Synthesis of pentacosasaccharide was
      accomplished in 77 steps with 0.0012 % overall yield. These oligosaccharides are
      envisioned to be excellent probes for understanding disease biology thereby
      facilitating discovery of novel antitubercular agents, vaccines and/or
      diagnostics.

PMID- 29072798
TI  - Characteristics of CA1 place fields in a complex maze with multiple choice
      points.
AB  - For the sake of rigorous control of task variables, hippocampal place cells have
      been usually studied in relatively simple environments. To approach the situation
      of real-life navigation in an urban-like environment, we recorded CA1 place cells
      while rats performance a memory task in a "Townmaze" with two start locations,
      three alternate paths in the maze midsection, followed by a two-way choice that
      determined the trial outcome, access to a goal compartment. Further, to test the
      ability of place cells to update their spatial representation upon local changes
      in the environment while maintaining the integrity of the overall spatial map to
      allow effective navigation, we occasionally introduced barriers in the maze mid
      section to force the rat to select a nonpreferred route. The "Townmaze" revealed
      many new interesting features of CA1 neurons. First, we found neurons with 3-5
      fields that appear to represent segments on a single common route through the
      maze. Second, we found neurons with 3-5 fields similarly aligned along the
      longitudinal or transverse maze axis. Responses to the barriers were assessed
      separately near and far from the barriers. Appearance of new fields in response
      to the barriers took place almost exclusively only locally near the barrier,
      whereas in-field firing rate changes occurred throughout the maze. Further, field
      location changes did not correlate with the task performance, whereas firing rate
      changes did. These findings suggest that in a complex environment with blocked
      distal views, CA1 neurons code for the environment as sequences of significant
      nodes but are also capable of extracting and associating common elements across
      these sequences.

PMID- 29072799
TI  - Sleep habits and non-alcoholic fatty liver disease: Risk assessment by adjusting
      confounders.

PMID- 29072800
TI  - Effect of sitagliptin on glucose control in type 2 diabetes mellitus after Roux
      en-Y gastric bypass surgery.
AB  - The present study was a 4-week randomized trial to assess the efficacy and safety
      of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring
      type 2 diabetes after Roux-en-Y gastric bypass surgery (RYGB). Participants (n =
      32) completed a mixed meal test (MMT) and self-monitoring of plasma glucose
      (SMPG) before and 4 weeks after randomization to either sitagliptin 100 mg daily
      or placebo daily. Questionnaires were administered to assess gastrointestinal
      discomfort. Outcome variables were glucose, active glucagon-like peptide-1 and
      beta-cell function during the MMT, and glucose levels during SMPG. Age (56.3 +/-
      8.2 years), body mass index (34.4 +/- 6.7 kg/m2 ), glycated haemoglobin (7.21 +/-
      0.77%), diabetes duration (12.9 +/- 10.0 years), years since RYGB (5.6 +/- 3.3
      years) and beta-cell function did not differ between the placebo and sitagliptin
      groups at pre-intervention. Sitagliptin was well tolerated, decreased
      postprandial glucose levels during the MMT (from 8.31 +/- 1.92 mmol/L to 7.67 +/-
      1.59 mmol/L, P = 0.03) and mean SMPG levels, but had no effect on beta-cell
      function. In patients with diabetes and mild hyperglycemia after RYGB, a short
      course of sitagliptin provided a small but significant glucose-lowering effect,
      with no identified improvement in beta-cell function.

PMID- 29072801
TI  - Microbiome facilitated pest resistance: potential problems and uses.
AB  - Microbiome organisms can degrade environmental xenobiotics including pesticides,
      conferring resistance to most types of pests. Some cases of pesticide resistance
      in insects, nematodes and weeds are now documented to be due to microbiome
      detoxification, and is a demonstrated possibility with rodents. Some cases of
      metabolic resistance may have been misattributed to pest metabolism, and not to
      organisms in the microbiome, because few researchers use axenic pests in studying
      pesticide metabolism. Instances of microbiomes evolving pesticide resistance
      contributing to resistance of their hosts may become more common due the erratic
      nature of climate change, as microbiome populations typically increase and evolve
      faster in stressful conditions. Conversely, microbiome organisms can be
      engineered to provide crops and beneficial insects with needed resistance to
      herbicides and insecticides, respectively, but there has not been sufficient
      efficacy to achieve commercial products useful at the field level, even with
      genetically engineered microbiome organisms. (c) 2017 Society of Chemical
      Industry.

PMID- 29072802
TI  - Mesoporous Carbon@Titanium Nitride Hollow Spheres as an Efficient SeS2 Host for
      Advanced Li-SeS2 Batteries.
AB  - The introduction of a certain proportion of selenium into sulfur-based cathodes
      is an effective strategy for enhancing the integrated battery performance.
      However, similar to sulfur, selenium sulfide cathodes suffer from poor cycling
      stability owing to the dissolution of reaction intermediate products. In this
      study, to exploit the advantages of SeS2 to the full and avoid its shortcomings,
      we designed and synthesized a hollow mesoporous carbon@titanium nitride (HMC@TiN)
      host for loading 70 wt % of SeS2 as a cathode material for Li-SeS2 batteries.
      Benefiting from both physical and chemical entrapment by hollow mesoporous carbon
      and TiN, the HMC@TiN/SeS2 cathode manifests high utilization of the active
      material and excellent cycling stability. Moreover, it exhibits promising areal
      capacity (up to 4 mAh cm-2 ) with stable cell performance in the high-mass
      loading electrode.

PMID- 29072803
TI  - The presence of F cells with a fetal phenotype in adults with hemoglobinopathies
      limits the utility of flow cytometry for quantitation of fetomaternal hemorrhage.
AB  - BACKGROUND: Detection and quantitation of fetomaternal hemorrhage (FMH) can be
      difficult in patients with pre-existing elevations of HbF, such as those with
      hemoglobinopathies. The aim of this study was to evaluate the utility of dual
      color flow cytometry with the Fetal Cell Count Kit (FCCK) in differentiating
      adult and fetal HbF in this population, as compared to flow cytometry (FC) using
      HbF alone. METHODS: Peripheral blood was obtained from normal adults and patients
      with hemoglobinopathies (beta-thalassemia and sickle cell disease), including a
      small number of pregnant females. Cord blood was used to spike some samples with
      5% fetal cells. Analysis by single color (HbF) and dual-color (HbF and carbonic
      anhydrase) FC was performed on these samples. Fetal cells were defined as those
      with high HbF fluorescence on single-color FC, and those that were HbF + CA-
      using the FCCK. The quantity of fetal cells detected by each technique was
      compared. RESULTS: Forty-six adult patients were included. In non-pregnant adults
      with hemoglobinopathies, a population of red cells with a fetal cell phenotype
      were detected by both techniques. The dual-color method reported lower quantities
      of these cells. In nineteen samples spiked with cord blood the FCCK consistently
      underestimated the quantity of fetal cells. CONCLUSIONS: Patients with beta
      thalassemia and sickle cell disease have a population of HbF-containing cells
      which are phenotypically similar to fetal cells. Even with dual-color flow
      cytometry (FCCK), the detection and quantification of FMH by flow cytometry in
      this population remains difficult. (c) 2017 International Clinical Cytometry
      Society.

PMID- 29072805
TI  - Zooming in on adipocytes: High and deep.

PMID- 29072806
TI  - Strategies for success: a multi-institutional study on robot-assisted partial
      nephrectomy for complex renal lesions.
AB  - OBJECTIVE: To describe our technique, illustrated with images and videos, of
      robot-assisted partial nephrectomy (RAPN) for challenging renal tumours. PATIENTS
      AND METHODS: A study of 249 patients who underwent RAPN in multiple institutions
      was performed. Patients were identified using prospective RAPN databases. Complex
      renal lesion were defined as those with a RENAL nephrometry score >=10. Data were
      analysed and differences among groups examined. RESULTS: A total of 31 (12.4%)
      RAPNs were performed for complex renal tumours. The median (interquartile range
      [IQR]) patient age was 57 (50.5-70.5) years and 21 patients (67.7%) were men. The
      median (IQR) American Society of Anesthesiologists score was 2 (2-3). The median
      (IQR) operating time was 200 (50-265) min, warm ischaemia time was 23 (18.5-29)
      min, and estimated blood loss was 200 (50-265) mL. There were no intra-operative
      complications. Two patients (6.4%) had postoperative complications. One patient
      (3.2%) had a positive surgical margin. The median (IQR) length of stay was 3.5 (3
      5) days and the median (IQR) follow-up was 12.5 (7-24) months. There were no
      recurrences. RAPN resulted in statistically significant changes in renal function
      3 months after RAPN compared with preoperative renal function (P < 0.001).
      CONCLUSION: Our results showed that RAPN was a safe approach for selected
      patients with complex renal tumours and may facilitate tumour resection and
      renorrhaphy for challenging cases, offering a minimally invasive surgical option
      for patients who may otherwise require open surgery.

PMID- 29072807
TI  - Are There Carbenes in N-Heterocyclic Carbene Organocatalysis?
AB  - Azolium cations are widely employed in organocatalysis to catalyse highly
      valuable synthetic processes in the presence of a base. These reactions are
      called "N-heterocyclic carbene catalysis", based on the assumption that they are
      initiated by the formation of a free carbene through deprotonation, which can
      then react with the substrates and thereby affect their reactivity to obtain the
      desired products. However, we herein provide evidence that an electrophilic
      aromatic substitution mechanism is energetically more favourable, in which the
      azolium cation reacts directly with the substrate, avoiding the formation of the
      free carbene in solution.

PMID- 29072804
TI  - Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G
      Associated Kinase.
AB  - 4-Anilinoquinolines were identified as potent and narrow-spectrum inhibitors of
      the cyclin G associated kinase (GAK), an important regulator of viral and
      bacterial entry into host cells. Optimization of the 4-anilino group and the 6,7
      quinoline substituents produced GAK inhibitors with nanomolar activity, over 50
      000-fold selectivity relative to other members of the numb-associated kinase
      (NAK) subfamily, and a compound (6,7-dimethoxy-N-(3,4,5-trimethoxyphenyl)quinolin
      4-amine; 49) with a narrow-spectrum kinome profile. These compounds may be useful
      tools to explore the therapeutic potential of GAK in prevention of a broad range
      of infectious and systemic diseases.

PMID- 29072808
TI  - A method permissive to fixation and permeabilization for the multiparametric
      analysis of apoptotic and necrotic cell phenotype by flow cytometry.
AB  - Annexin-V/propidium iodide method (A-V/PI) is a common flow cytometric method for
      the multiparametric analysis of cells in apoptosis. However, A-V/PI does not
      permit fixation and/or permeabilization of cells making impossible evaluation of
      intracellular markers, restricting the analysis in a narrow time frame after
      staining and excluding the possibility to study pathogen-infected cells. We
      developed a method permitting fixation and permeabilization of stained cells:
      Fixed Apoptotic/Necrotic (FAN) cells test. FAN relies on the same principle of A
      V/PI, but uses reagents that maintain their binding and fluorescence
      characteristics after fixation/permeabilization: a fluorochrome-labeled anti
      phosphatidylserine antibody and fluorescent amine-binding dyes. FAN was tested to
      discriminate apoptotic and necrotic cells using different stimuli on several cell
      types and results were always comparable to those obtained using A-V/PI. FAN,
      unlike A-V/PI, permitted to correlate cell death with intracellular and surface
      markers expression and to perform cytometry even two weeks after sample
      preparation. As fixation of stained cells inactivates infective pathogens, we
      used FAN in an in vitro model of Mycobacterium tuberculosis (Mtb) infection of
      macrophages to monitor cellular infection and cell death induction. Using a red
      fluorescent Mtb, fluorochrome labeled anti-TNF-alpha and anti-MHC class II
      monoclonal antibodies, FAN permitted to establish that the extent of macrophage
      death correlates with intracellular Mtb content and that dying cells accumulate
      TNF-alpha and down-modulate MHC class II molecules. Results suggest that FAN may
      represent an additional tool to study programmed cell death particularly useful
      when fixation procedures are required for a safe infected sample analysis or to
      comparatively analyze multiple samples. (c) 2017 International Society for
      Advancement of Cytometry.

PMID- 29072809
TI  - Overcoming the Lack of Oral Availability of Cyclic Hexapeptides: Design of a
      Selective and Orally Available Ligand for the Integrin alphavbeta3.
AB  - A highly systematic approach for the development of both orally bioavailable and
      bioactive cyclic N-methylated hexapeptides as high affinity ligands for the
      integrin alphavbeta3 is based on two concepts: a) screening of systematically
      designed libraries with spatial diversity and b) masking of the peptide charge
      with a lipophilic protecting group. The key steps of the method are 1) initial
      design of a combinatorial library of N-methylated analogues of the stem peptide
      cyclo(d-Ala-Ala5 ); 2) selection of cyclic peptides with the highest intestinal
      permeability; 3) design of sublibraries with the bioactive RGD sequence in all
      possible positions; 4) selection of the best ligands for RGD-recognizing integrin
      subtypes; 5) fine-tuning of the affinity and selectivity by additional Ala to Xaa
      substitutions; 6) protection of the charged functional groups according to the
      prodrug concept to regain intestinal and oral permeability; 7) proof of
      biological effects in mice after oral administration.

PMID- 29072811
TI  - Social cytopathology: Building a stronger cytopathology community through social
      media.

PMID- 29072812
TI  - Anti-interleukin-1 therapy has mild hypoglycaemic effect in type 2 diabetes.
AB  - The aim of this study was to systematically evaluate the efficacy and safety of
      anti-interleukin-1 therapy for type 2 diabetes. A literature search of PubMed and
      Embase for available trials on anti-interleukin-1 therapy in type 2 diabetes was
      performed. The baseline characteristics, changes in HbA1c and other metabolic
      parameters, and adverse events were extracted from included randomized controlled
      trials (RCTs) and were analysed with Review Manager. Mean differences (MDs) and
      95% confidence intervals (Cis) were calculated to measure differences in
      metabolic parameters. Odds ratio and 95% CIs were calculated for adverse event
      rates. Five RCTs were included in the current meta-analysis with 357 subjects
      undergoing anti-interleukin-1 therapy (IL-1 receptor antagonist or anti-IL-1beta
      antibody) and 221 controls who received placebo. The HbA1c decrement (%) of anti
      interleukin-1 group was significantly higher than that of the placebo group (MD =
      0.23; 95% CI, -0.39 to -0.07; P = .005). AUC of C-peptide was improved also (MD =
      14.55; 95% CI, 1.81-27.28; P = .03) after anti-interleukin-1 intervention. There
      was no difference in the rate of adverse events (odds ratio,1.16; 95% CI, 0.90
      1.49; P = .25) between 2 groups. Anti-interleukin-1 therapy has mild
      hypoglycaemic effect in type 2 diabetes.

PMID- 29072813
TI  - A high-throughput all-optical laser-scanning imaging flow cytometer with
      biomolecular specificity and subcellular resolution.
AB  - Image-based cellular assay advances approaches to dissect complex cellular
      characteristics through direct visualization of cellular functional structures.
      However, available technologies face a common challenge, especially when it comes
      to the unmet need for unraveling population heterogeneity at single-cell
      precision: higher imaging resolution (and thus content) comes at the expense of
      lower throughput, or vice versa. To overcome this challenge, a new type of
      imaging flow cytometer based upon an all-optical ultrafast laser-scanning imaging
      technique, called free-space angular-chirp-enhanced delay (FACED) is reported. It
      enables an imaging throughput (>20 000 cells s-1 ) 1 to 2 orders of magnitude
      higher than the camera-based imaging flow cytometers. It also has 2 critical
      advantages over optical time-stretch imaging flow cytometry, which achieves a
      similar throughput: (1) it is widely compatible to the repertoire of biochemical
      contrast agents, favoring biomolecular-specific cellular assay and (2) it enables
      high-throughput visualization of functional morphology of individual cells with
      subcellular resolution. These capabilities enable multiparametric single-cell
      image analysis which reveals cellular heterogeneity, for example, in the cell
      death processes demonstrated in this work-the information generally masked in non
      imaging flow cytometry. Therefore, this platform empowers not only efficient
      large-scale single-cell measurements, but also detailed mechanistic analysis of
      complex cellular processes.

PMID- 29072814
TI  - Multiple resistance to glyphosate, paraquat and ACCase-inhibiting herbicides in
      Italian ryegrass populations from California: confirmation and mechanisms of
      resistance.
AB  - BACKGROUND: Glyphosate, paraquat and acetyl CoA carboxylase (ACCase)-inhibiting
      herbicides are widely used in California annual and perennial cropping systems.
      Recently, glyphosate, paraquat, and ACCase- and acetolactate synthase (ALS)
      inhibitor resistance was confirmed in several Italian ryegrass populations from
      the Central Valley of California. This research characterized the possible
      mechanisms of resistance. RESULTS: Multiple-resistant populations (MR1, MR2) are
      resistant to several herbicides from at least three modes of action. Dose
      response experiments revealed that the MR1 population was 45.9-, 122.7- and 20.5
      fold, and the MR2 population was 24.8-, 93.9- and 4.0-fold less susceptible to
      glyphosate, sethoxydim and paraquat, respectively, than the susceptible (Sus)
      population. Accumulation of shikimate in Sus plants was significantly greater
      than in MR plants 32 h after light pretreatments. Glyphosate resistance in MR
      plants was at least partially due to Pro106-to-Ala and Pro106-to-Thr
      substitutions at site 106 of 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS).
      EPSPS gene copy number and expression level were similar in plants from the Sus
      and MR populations. An Ile1781-to-Leu substitution in ACCase gene of MR plants
      conferred a high level of resistance to sethoxydim and cross-resistance to other
      ACCase-inhibitors. Radiolabeled herbicide studies and phosphorimaging indicated
      that MR plants had restricted translocation of 14 C-paraquat to untreated leaves
      compared to Sus plants. CONCLUSION: This study shows that multiple herbicide
      resistance in Italian ryegrass populations in California, USA, is due to both
      target-site and non-target-site resistance mechanisms. (c) 2017 Society of
      Chemical Industry.

PMID- 29072810
TI  - Serotonin neuron development: shaping molecular and structural identities.
AB  - The continuing fascination with serotonin (5-hydroxytryptamine, 5-HT) as a
      nervous system chemical messenger began with its discovery in the brains of
      mammals in 1953. Among the many reasons for this decades-long interest is that
      the small numbers of neurons that make 5-HT influence the excitability of neural
      circuits in nearly every region of the brain and spinal cord. A further reason is
      that 5-HT dysfunction has been linked to a range of psychiatric and neurological
      disorders many of which have a neurodevelopmental component. This has led to
      intense interest in understanding 5-HT neuron development with the aim of
      determining whether early alterations in their generation lead to brain disease
      susceptibility. Here, we present an overview of the neuroanatomical organization
      of vertebrate 5-HT neurons, their neurogenesis, and prodigious axonal
      architectures, which enables the expansive reach of 5-HT neuromodulation in the
      central nervous system. We review recent findings that have revealed the
      molecular basis for the tremendous diversity of 5-HT neuron subtypes, the impact
      of environmental factors on 5-HT neuron development, and how 5-HT axons are
      topographically organized through disparate signaling pathways. We summarize
      studies of the gene regulatory networks that control the differentiation,
      maturation, and maintenance of 5-HT neurons. These studies show that the
      regulatory factors controlling acquisition of 5-HT-type transmitter identity
      continue to play critical roles in the functional maturation and the maintenance
      of 5-HT neurons. New insights are presented into how continuously expressed 5-HT
      regulatory factors control 5-HT neurons at different stages of life and how the
      regulatory networks themselves are maintained. WIREs Dev Biol 2018, 7:e301. doi:
      10.1002/wdev.301 This article is categorized under: Nervous System Development >
      Vertebrates: General Principles Gene Expression and Transcriptional Hierarchies >
      Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies >
      Cellular Differentiation Nervous System Development > Secondary: Vertebrates:
      Regional Development.

PMID- 29072816
TI  - High-grade urothelial carcinoma in urine cytology with jet black and smooth or
      glassy chromatin.
AB  - BACKGROUND: Some high-grade urothelial carcinomas (UCs) in urine cytology can
      have jet black, smooth, or glassy chromatin, but to the authors' knowledge, the
      incidence and criteria for diagnosis are not well described. The current study
      was performed to define the incidence and appearance of high-grade UC in urine
      cytology in cytospin preparations with jet black and smooth or glassy chromatin.
      METHODS: Cytospin preparations from 331 cases with biopsy follow-up (230
      benign/low-grade UCs and 101 malignant UCs) were reviewed. RESULTS: Cases with
      malignant cells with jet black and smooth or glassy chromatin were identified in
      a total of 60 cases (59.4% of all malignancies). These comprised 18 carcinoma in
      situ cases, 28 high-grade papillary UCs, 8 invasive UCs, 3 squamous cell
      carcinomas, 2 adenocarcinomas, and 1 melanoma. Of the 93 high-grade UCs, 51
      (54.8%) had cells with either jet black and smooth or glassy chromatin. These
      cells were the only type of malignant cell in 6 of 101 cases (5.9%). All cases
      had at least 50 cells with jet black nuclei. Nuclei with jet black and smooth
      chromatin often were smaller than normal urothelial cells, often but not always
      elongate, had irregular nuclear outlines including pointed areas, and usually
      were accompanied by necrosis. Cells with glassy chromatin often were larger than
      normal urothelial cells, had rounder but still irregular nuclei, and also had
      frequent necrosis. CONCLUSIONS: Malignant urothelial cells in urine cytology with
      jet black chromatin are common and can be diagnosed as "positive for malignancy"
      based on their irregular nuclear outline, increased cellularity (>=50 abnormal
      cells), and frequent necrosis. Cancer Cytopathol 2018;126:64-8. (c) 2017 American
      Cancer Society.

PMID- 29072815
TI  - Zinc supplementation in prediabetes: A randomized double-blind placebo-controlled
      clinical trial.
AB  - BACKGROUND: This study evaluated the effects of zinc supplementation on glycemic
      control, other cardiometabolic and anthropometric parameters, and disease
      progression in prediabetes. METHODS: A randomized double-blind placebo-controlled
      Phase 2 clinical trial was conducted over a 12-month period in 200 subjects (43%
      male; mean [+/- SD] age 51.8 +/- 7.3 years), randomly assigned (1:  1) to the
      treatment or control group. The treatment group received zinc (20 mg daily).
      Subjects were evaluated at baseline and at 1, 3, 6, and 12 months. The primary
      outcome was the change in glycemic control from baseline. Multiple regression
      analyses were performed, with change in outcome variables after intervention from
      baseline used as continuous dependent variables. RESULTS: In both groups, mean
      serum zinc concentrations prior to the trial were below normal (15.29-21.41
      MUmol/L). During the 12-month follow-up, a significantly higher percentage of
      participants developed type 2 diabetes in the control compared with zinc-treated
      group (25.0% vs 11.0% respectively; P = 0.016). Fasting plasma glucose (FPG), 2-h
      glucose levels in the oral glucose tolerance test (OGTT), homeostasis model
      assessment of insulin resistance (HOMA-IR), total cholesterol (TC), and low
      density lipoprotein cholesterol (LDL-C) were significantly lower in the treated
      group, with significant improvement in beta-cell function. In all four regression
      models, the best predictor of the dependent variables (i.e. change in FPG, 2-h
      glucose in the OGTT, HOMA-IR, and homeostatic model assessment of beta-cell
      function) was zinc treatment. CONCLUSIONS: Zinc supplementation reduced blood
      glucose and insulin resistance while improving beta-cell function. Furthermore,
      supplementation reduced disease progression to diabetes and had beneficial
      effects on TC and LDL-C.

PMID- 29072818
TI  - Isolation, cultivation, and characterization of human mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) exhibit a high self-renewal capacity, multilineage
      differentiation potential and immunomodulatory properties. This set of
      exceptional features makes them an attractive tool for research and clinical
      application. However, MSC are far from being a uniform cell type, which makes
      standardization difficult. The exact properties of human MSC (hMSC) can vary
      greatly depending on multiple parameters including tissue source, isolation
      method and medium composition. In this review we address the most important
      influence factors. We highlight variations in the differentiation potential of
      MSC from different tissue sources. Furthermore, we compare enzymatic isolation
      strategies with explants cultures focusing on adipose tissue and umbilical cords
      as two relevant examples. Additionally, we address effects of medium composition
      and serum supplementation on MSC expansion and differentiation. The lack of
      standardized methods for hMSC isolation and cultivation mandates careful
      evaluation of different protocols regarding efficiency and cell quality. MSC
      characterization based on a set of minimal criteria defined by the International
      Society for Cellular Therapy is a widely accepted practice, and additional
      testing for MSC functionality can provide valuable supplementary information. The
      MSC secretome has been identified as an important signaling mechanism to affect
      other cells. In this context, extracellular vesicles (EVs) are attracting
      increasing interest. The thorough characterization of MSC-derived EVs and their
      interaction with target cells is a crucial step toward a more complete
      understanding of MSC-derived EV functionality. Here, we focus on flow cytometric
      approaches to characterize free as well as cell bound EVs and address potential
      differences in the bioactivity of EVs derived from stem cells from different
      sources. (c) 2017 International Society for Advancement of Cytometry.

PMID- 29072817
TI  - The impact of the global bacille Calmette-Guerin shortage on treatment patterns:
      population-based data.

PMID- 29072819
TI  - Semi-physiological model of postprandial triglyceride response in lean, obese and
      very obese individuals after a high-fat meal.
AB  - AIMS: To quantify the postprandial triglyceride (TG) response of chylomicrons and
      very-low-density lipoprotein-V6 (VLDL-V6) after a high-fat meal in lean, obese
      and very obese healthy individuals, using a mechanistic population lipokinetic
      modelling approach. METHODS: Healthy individuals from three body mass index
      population categories: lean (18.5-24.9 kg/m2 ), obese (30-33 kg/m2 ), and very
      obese (34-40 kg/m2 ) were enrolled in a clinical study to assess the TG response
      after a high-fat meal, containing 60% fat. Non-linear mixed-effect modelling was
      used to analyse the TG concentrations of chylomicrons and large VLDL-V6
      particles. RESULTS: The TGs in chylomicrons and VLDL-V6 particles had a prominent
      postprandial peak and represented the majority of the postprandial response; only
      the VLDL-V6 showed a difference across the populations. A turn-over model
      successfully described the TG concentration-time profiles of both chylomicrons
      and large VLDL-V6 particles after the high-fat meal. This model consisted of four
      compartments: two transit compartments for the lag between meal consumption and
      appearance of TGs in the blood, and one compartment each for the chylomicrons and
      large VLDL-V6 particles. The rate constants for the production of chylomicrons
      and elimination of large VLDL-V6 particles, along with the conversion rate of
      chylomicrons to large VLDL-V6 particles were well defined. CONCLUSIONS: This is
      the first lipokinetic model to describe the absorption of TGs from dietary fats
      into the blood stream and compares the dynamics of TGs in chylomicrons and large
      VLDL-V6 particles among lean, obese and very obese people. Such a model can be
      used to identify where pharmacological therapies act, thereby improving the
      determination of efficacy, and identifying complementary mechanisms for
      combinational drug therapies.

PMID- 29072820
TI  - Targeting postprandial glycaemia in children with diabetes: Opportunities and
      challenges.
AB  - Postprandial glycaemia makes a substantial contribution to overall glycaemic
      control in diabetes, particularly in patients whose preprandial glycaemia is
      relatively well controlled and glycated haemoglobin (HbA1c) only modestly
      elevated. Our review addresses the determinants of postprandial glycaemia and how
      it may be targeted therapeutically in children with diabetes. Postprandial
      glycaemia is influenced by preprandial glycaemia, macronutrients and their
      absorption, insulin delivery and sensitivity, the action of the enteroendocrine
      system, and the rate of gastric emptying. Contemporary continuous glucose
      monitoring systems reveal patterns of post prandial glycaemia and allow
      management to be guided more precisely. Delays in blood glucose determination,
      insulin delivery and its absorption remain challenges in the rapidly evolving
      closed loop continuous subcutaneous insulin and glucagon delivery systems
      developed for children with type 1 diabetes. Augmentation of the incretin system
      through nutritional preloads or incretin mimetics targets postprandial glycaemia
      by slowing gastric emptying as well as insulinotropic and glucagonostatic
      effects. These treatments are of particular relevance to children with type 2
      diabetes. Following the development of targeted therapies in adults, postprandial
      blood glucose control will now be increasingly targeted in the treatment of
      diabetes in children.

PMID- 29072822
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 45/2017.

PMID- 29072823
TI  - Corrigendum: Benign-by-Design Solventless Mechanochemical Synthesis of Three-,
      Two-, and One-Dimensional Hybrid Perovskites.

PMID- 29072821
TI  - Characterization of field-evolved resistance to Bacillus thuringiensis-derived
      Cry1F delta-endotoxin in Spodoptera frugiperda populations from Argentina.
AB  - BACKGROUND: Transgenic maize (Zea mays L.) event TC1507 (Herculex(r) I insect
      protection), expressing Cry1F delta-endotoxin derived from Bacillus thuringiensis
      var. aizawai, was commercialized in 2003 in the Americas. Spodoptera frugiperda
      (J.E. Smith) (Lepidoptera: Noctuidae) susceptibility to Cry1F was monitored
      annually across several regions in Argentina using diagnostic concentration
      bioassays. Reduced performance of TC1507 maize against S. frugiperda was reported
      in 2013. A resistant population was established in the laboratory and the
      dominance of Cry1F resistance was characterized. RESULTS: During 2012-2015, high
      survivorship of several populations was observed in the resistance monitoring
      program. Reciprocal crosses of a Cry1F-resistant population with a Cry1F
      susceptible population were evaluated to calculate effective dominance (DML )
      based on mortality levels observed at 100 ug/ml Cry1F. Two additional dominance
      levels (DLC and DEC ) were calculated using lethal (LC50 ) or effective
      concentration (EC50 ) derived from concentration-response bioassays. Estimates
      indicated that Cry1F resistance in S. frugiperda in Argentina was either highly
      recessive (DML = 0.005) or incompletely recessive (DLC < 0.26 and DEC < 0.19).
      CONCLUSION: This study is the first documented confirmation and characterization
      of S. frugiperda Cry1F field-evolved resistance in Argentina. The resistance to
      Cry1F in S. frugiperda populations collected in Argentina, is autosomal and
      incompletely recessive similar to the resistance reported in Brazil. (c) 2017 The
      Authors. Pest Management Science published by John Wiley (c) Sons Ltd on behalf
      of Society of Chemical Industry.

PMID- 29072825
TI  - Nutrition and the transplant candidate.
AB  - Cirrhosis is the most common indication for liver transplantation (LT) worldwide.
      Malnutrition is present in at least two-thirds of patients with cirrhosis
      awaiting LT. It negatively impacts survival, quality of life, and the ability to
      respond to stressors, such as infection and surgery. Muscle wasting or sarcopenia
      is the most objective feature of chronic protein malnutrition in cirrhosis, and
      this condition is associated with increased morbidity and mortality before and
      after LT. In addition to its objectivity, muscularity assessment with cross
      sectional imaging studies is a useful marker of nutritional status in LT
      candidates, as sarcopenia reflects a chronic decline in the general physical
      condition, rather than acute severity of the liver disease. Despite the high
      prevalence and important prognostic role, malnutrition and sarcopenia are
      frequently overlooked because standards for nutritional assessment are lacking
      and challenges such as fluid retention and obesity are prevalent. In this review,
      current diagnostic methods to evaluate malnutrition, including muscle
      abnormalities in cirrhosis, are discussed and current knowledge regarding the
      incidence and clinical impact of malnutrition in cirrhosis and its impact after
      LT are presented. Existing and potential novel therapeutic strategies for
      malnutrition in cirrhosis are also discussed, emphasizing the treatment of muscle
      wasting in the LT candidate in an effort to improve survival while waiting for LT
      and to reduce morbidity and mortality after LT.Liver Transplantation 23 1451-1464
      2017 AASLD.

PMID- 29072826
TI  - College Students' Sexual Consent Communication And Perceptions of Sexual Double
      Standards: A Qualitative Investigation.
AB  - CONTEXT: Affirmative consent standards adopted by colleges and universities are
      meant to decrease miscommunication that may lead to sexual assault. However, they
      may not take into account sociocultural factors that influence consent. In
      particular, the role of gender norms needs to be better understood. METHODS: In
      depth interviews about college students' sexual activity, including sexual
      consent communication, were conducted with 17 female and 13 male students at a
      large southern university during the spring 2013 semester. The interview protocol
      and analyses were guided by Carspecken's critical qualitative methodology, which
      seeks to understand both participants' explicit statements and implied underlying
      meanings and values. Themes and subthemes were identified through inductive
      analyses. RESULTS: Two overarching themes emerged: Students perceived a sexual
      double standard, and males viewed obtaining sex as a conquest. Subthemes related
      to the first theme reflected endorsement of traditional views of women's
      sexuality (the notions that "good girls" do not have sex, that women should
      privilege men's sexual needs over their own and that women "owe" men sex once men
      have "worked" for it). Subthemes related to the second theme reflected males'
      beliefs that sex is a commodity that pits women and men against one another, and
      that women can be "convinced" to have sex if they initially refuse. CONCLUSIONS:
      College students' consent communication may be influenced by gender norms that
      challenge assumptions of affirmative consent standards. Cultural shifts in
      students' views of sexuality may be necessary for affirmative consent policies to
      be effective.

PMID- 29072827
TI  - Construction of a novel electrochemical sensor based on molecularly imprinted
      polymers for the selective determination of chlorpyrifos in real samples.
AB  - We present a novel electrochemical sensor based on an electrode modified with
      molecularly imprinted polymers for the detection of chlorpyrifos. The modified
      electrode was constructed by the synthesis of molecularly imprinted polymers by a
      precipitation method then coated on a glassy carbon electrode. The surface
      morphology of the modified electrode was characterized by using field-emission
      scanning electron microscopy and transmission electron microscopy. The
      performance of the imprinted sensor was thoroughly investigated by using cyclic
      voltammetry and differential pulse voltammetry. The imprinted electrochemical
      sensor displayed high repeatability, stability, and selectivity towards the
      template molecules. Under the optimal experimental conditions, the peak current
      response of the imprinted electrochemical sensor was linearly related to the
      concentration of chlorpyrifos over the range 1 * 10-10 -1 * 10-5  mol/L with a
      limit of detection of 4.08 * 10-9  mol/L (signal-to-noise ratio = 3).
      Furthermore, the proposed molecularly imprinted electrochemical sensor was
      applied to the determination of chlorpyrifos in the complicated matrixes of real
      samples with satisfactory results. Therefore, the molecularly imprinted polymers
      based electrochemical sensor might provide a highly selective, rapid, and cost
      effective method for chlorpyrifos determination and related analysis.

PMID- 29072824
TI  - Introduction of a putative biocontrol agent into a range of phytoplasma- and
      liberibacter-susceptible crop plants.
AB  - BACKGROUND: Phytoplasma, the causative agent of Bois Noir disease of grapevines,
      are vectored by the planthopper Hyalesthes obsoletus (Hemiptera: Cixiidae). A
      Dyella-like bacterium (DLB) isolated from H. obsoletus inhibits the growth of
      Spiroplasma melliferum, a cultivable relative of phytoplasma. Additional evidence
      suggests that DLB can reduce the symptoms of yellows disease in grapevine
      plantlets. The aim of this study was to test whether DLB could colonize a range
      of phytoplasma- and liberibacter-sensitive crop plants, and thus assess its
      potential agricultural use. RESULTS: Vitex agnus-castus, the preferred host plant
      of H. obsoletus was found to be a natural host of DLB, which was successfully
      introduced into a range of crop plants belonging to seven families. The most
      effective DLB application method was foliar spraying. Microscopy observation
      revealed that DLB aggregated on the leaf surface and around the stomata,
      suggesting that this is its route of entry. DLB was also present in the vascular
      tissues of plants, indicating that it moved systemically through the plant.
      CONCLUSIONS: DLB is a potential biocontrol agent and its broad spectrum of host
      plants indicates the possibility of its future use against a range of diseases
      caused by phloem-limited bacteria. (c) 2017 Society of Chemical Industry.

PMID- 29072828
TI  - Microtubular Self-Assembly of Covalent Organic Frameworks.
AB  - Despite significant progress in the synthesis of covalent organic frameworks
      (COFs), reports on the precise construction of template-free nano- and
      microstructures of such materials have been rare. In the quest for dye-containing
      porous materials, a novel conjugated framework DPP-TAPP-COF with an enhanced
      absorption capability up to lambda=800 nm has been synthesized by utilizing
      reversible imine condensations between 5,10,15,20-tetrakis(4
      aminophenyl)porphyrin (TAPP) and a diketopyrrolopyrrole (DPP) dialdehyde
      derivative. Surprisingly, the obtained COF exhibited spontaneous aggregation into
      hollow microtubular assemblies with outer and inner tube diameters of around 300
      and 90 nm, respectively. A detailed mechanistic investigation revealed the time
      dependent transformation of initial sheet-like agglomerates into the tubular
      microstructures.

PMID- 29072829
TI  - Actual Daily Intakes of Tea Catechins and Thier Estimation According to Four
      Season 3 Day Weighed Dietary Records and a Short Food Frequency Questionnaire
      among Japanese Men and Women
AB  - Background: Tea catechins are considered to be important preventive factors of
      cancer on several organs; however,the relationships of the actual daily intakes
      (ADIs) on the preventive effects have not been adequately addressed. Wemeasured
      the ADIs of tea catechins as annual averages derived from every their ingested
      cups recorded by each subject,and the estimation models were established
      considering tea origin. Methods: Fifty-nine Japanese men and womencompleted four
      season 3 day weighed dietary records (WDRs) and a food frequency questionnaire
      (FFQ), and samplesof green, oolong and black teas, ingested during a total 12
      days were collected for the analysis. The ADIs of the total andcomposed catechins
      of all tea samples were measured by a high-performance liquid chromatography. The
      estimationmodels for the ADIs (R2: coefficient of determination) based on the
      WDRs and FFQ were established with multipleregression analysis using appropriate
      confounding factors. Results: The ADIs of total catechins and
      epigallocatechingallate (EGCg) were 110 and 21.4 mg/day in men and 157 and 34.7
      mg/day in women, respectively. The total catechinsADIs were positively associated
      with green tea consumption based on WDRs and FFQ (adjusted R2 =0.421 and 0.341for
      men and 0.346 and 0.238 for women, p<0.05 for all, respectively). Likewise, the
      EGCg ADIs were associated withgreen tea intake derived from WDRs and FFQ,
      respectively. Conclusions: We revealed the ADIs of total catechinsand EGCg as
      annual averages could establish their estimation models. These provide reference
      information to clarifytheir relationships with cancer risks.

PMID- 29072831
TI  - A SOA-Based Platform to Support Clinical Data Sharing
AB  - The eSource Data Interchange Group, part of the Clinical Data Interchange
      Standards Consortium, proposed five scenarios to guide stakeholders in the
      development of solutions for the capture of eSource data. The fifth scenario was
      subdivided into four tiers to adapt the functionality of electronic health
      records to support clinical research. In order to develop a system belonging to
      the "Interoperable" Tier, the authors decided to adopt the service-oriented
      architecture paradigm to support technical interoperability, Health Level Seven
      Version 3 messages combined with LOINC (Logical Observation Identifiers Names and
      Codes) vocabulary to ensure semantic interoperability, and Healthcare Services
      Specification Project standards to provide process interoperability. The
      developed architecture enhances the integration between patient-care practice and
      medical research, allowing clinical data sharing between two hospital information
      systems and four clinical data management systems/clinical registries. The core
      is formed by a set of standardized cloud services connected through standardized
      interfaces, involving client applications. The system was approved by a medical
      staff, since it reduces the workload for the management of clinical trials.
      Although this architecture can realize the "Interoperable" Tier, the current
      solution actually covers the "Connected" Tier, due to local hospital policy
      restrictions.

PMID- 29072830
TI  - Preliminary Results: Colorectal Cancer Screening Using Fecal Immunochemical Test
      (FIT) in a Thai Population Aged 45-74 Years: A Population-Based Randomized
      Controlled Trial
AB  - Objective: The aim of this paper is to provide some details and the results to
      date of a colorectal cancer screening trialusing a fecal immunochemical test
      (FIT). Methods: A population-based randomized controlled trial began in May,
      2016.All people aged 45 to 74 years living in Nam Phong District, Khon Kaen
      Province, Thailand, and willing to participateare being recruited using an
      outreach method. Enrolled participants are randomly allocated by a computer
      generatedrandomization program either to a study arm (receive sample kit for FIT)
      or to a control arm (no provision of kit).Positive FIT cases are subsequently
      confirmed by a colonoscopy examination, and negative FIT cases are re-testedwith
      FIT every two years. The preliminary results to date were analysed using
      descriptive statistics. Results: A totalof 1,060 enrolled participants provided a
      complete set of data. Of those randomly assigned to the study arm and testedby
      FIT, 92 (8.7%) were found to be positive, 39 (11.5%) males and 53 (7.4%) females.
      The f-Hb concentrations atthe 75th, 90th and 95th percentiles for all age groups
      were higher in males than in females, and the distributions off-Hb concentration
      varied with age, especially at the 95th percentile where f-Hb concentrations
      increased with age.Conclusion: The preliminary results of our screening trial
      have indicated that the prevalence of positive FIT cases ishigher than in a
      similar recent and, at the time unique, previous study in Thailand. This finding
      is especially the casefor males and those in the older age groups.

PMID- 29072832
TI  - Experimental Study on the Mechanical Properties of Porcine Cartilage with
      Microdefect under Rolling Load
AB  - Objectives: To investigate the mechanical responses of microdefect articular
      cartilage under rolling load and find out the failure rule. Methods: Rolling load
      was applied to the porcine articular cartilage samples with rectangular notches
      of different depths. The displacement and strain near the notches were obtained
      by the noncontact digital image correlation technique. Results: The strain value
      and peak frequency around the notch increased; the maximum equivalent strain
      value could be observed at both bottom corners of the notch; the equivalent
      strain value first increased and then decreased at the points in the superficial
      and middle layers with the increase of rolling velocity; the points in the deep
      layer were less affected by rolling velocity; the equivalent strain value of the
      points in the superficial layer declined after rising with the increase of defect
      depth, while a decreased trend could be found for the points in the middle and
      deep layers. Conclusions: The shear strain, which rose with the increase in
      defect depth, was the main factor in cartilage destruction. The cartilage tended
      to be destructed firstly at the bottom corner of the defect. Rolling velocity
      showed significant effects on superficial and middle layers. Cartilage had the
      ability to resist destruction.

PMID- 29072834
TI  - Light-Regulated Synthesis of Cyclic-di-GMP by a Bidomain Construct of the
      Cyanobacteriochrome Tlr0924 (SesA) without Stable Dimerization.
AB  - Phytochromes and cyanobacteriochromes (CBCRs) use double-bond photoisomerization
      of their linear tetrapyrrole (bilin) chromophores within cGMP-specific
      phosphodiesterases/adenylyl cyclases/FhlA (GAF) domain-containing photosensory
      modules to regulate activity of C-terminal output domains. CBCRs exhibit
      photocycles that are much more diverse than those of phytochromes and are often
      found in large modular proteins such as Tlr0924 (SesA), one of three blue light
      regulators of cell aggregation in the cyanobacterium Thermosynechococcus
      elongatus. Tlr0924 contains a single bilin-binding GAF domain adjacent to a C
      terminal diguanylate cyclase (GGDEF) domain whose catalytic activity requires
      formation of a dimeric transition state presumably supported by a multidomain
      extension at its N-terminus. To probe the structural basis of light-mediated
      signal propagation from the photosensory input domain to a signaling output
      domain for a representative CBCR, these studies explore the properties of a
      bidomain GAF-GGDEF construct of Tlr0924 (Tlr0924Delta) that retains light
      regulated diguanylate cyclase activity. Surprisingly, circular dichroism
      spectroscopy and size exclusion chromatography data do not support formation of
      stable dimers in either the blue-absorbing 15ZPb dark state or the green
      absorbing 15EPg photoproduct state of Tlr0924Delta. Analysis of variants
      containing site-specific mutations reveals that proper signal transmission
      requires both chromophorylation of the GAF domain and individual residues within
      the amphipathic linker region between GAF and GGDEF domains. On the basis of
      these data, we propose a model in which bilin binding and light signals are
      propagated from the GAF domain via the linker to alter the equilibrium and
      interconversion dynamics between active and inactive conformations of the GGDEF
      domain to favor or disfavor formation of catalytically competent dimers.

PMID- 29072836
TI  - Fabrication, Detection, and Operation of a Three-Dimensional Nanomagnetic
      Conduit.
AB  - Three-dimensional (3D) nanomagnetic devices are attracting significant interest
      due to their potential for computing, sensing, and biological applications.
      However, their implementation faces great challenges regarding fabrication and
      characterization of 3D nanostructures. Here, we show a 3D nanomagnetic system
      created by 3D nanoprinting and physical vapor deposition, which acts as a conduit
      for domain walls. Domains formed at the substrate level are injected into a 3D
      nanowire, where they are controllably trapped using vectorial magnetic fields. A
      dark-field magneto-optical method for parallel, independent measurement of
      different regions in individual 3D nanostructures is also demonstrated. This work
      will facilitate the advanced study and exploitation of 3D nanomagnetic systems.

PMID- 29072835
TI  - Biological Studies and Target Engagement of the 2- C-Methyl-d-Erythritol 4
      Phosphate Cytidylyltransferase (IspD)-Targeting Antimalarial Agent (1 R,3 S)
      MMV008138 and Analogs.
AB  - Malaria continues to be one of the deadliest diseases worldwide, and the
      emergence of drug resistance parasites is a constant threat. Plasmodium parasites
      utilize the methylerythritol phosphate (MEP) pathway to synthesize isopentenyl
      pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which are essential
      for parasite growth. Previously, we and others identified that the Malaria Box
      compound MMV008138 targets the apicoplast and that parasite growth inhibition by
      this compound can be reversed by supplementation of IPP. Further work has
      revealed that MMV008138 targets the enzyme 2- C-methyl-d-erythritol 4-phosphate
      cytidylyltransferase (IspD) in the MEP pathway, which converts MEP and cytidine
      triphosphate (CTP) to cytidinediphosphate methylerythritol (CDP-ME) and
      pyrophosphate. In this work, we sought to gain insight into the structure
      activity relationships by probing the ability of MMV008138 analogs to inhibit
      PfIspD recombinant enzyme. Here, we report PfIspD inhibition data for
      fosmidomycin (FOS) and 19 previously disclosed analogs and report parasite growth
      and PfIspD inhibition data for 27 new analogs of MMV008138. In addition, we show
      that MMV008138 does not target the recently characterized human IspD, reinforcing
      MMV008138 as a prototype of a new class of species-selective IspD-targeting
      antimalarial agents.

PMID- 29072833
TI  - Radical Breakthroughs in Natural Product and Cofactor Biosynthesis.
AB  - The radical SAM (S-adenosyl-l-methionine) superfamily is one of the largest group
      of enzymes with >113000 annotated sequences [Landgraf, B. J., et al. (2016) Annu.
      Rev. Biochem. 85, 485-514]. Members of this superfamily catalyze the reductive
      cleavage of SAM using an oxygen sensitive 4Fe-4S cluster to transiently generate
      5'-deoxyadenosyl radical that is subsequently used to initiate diverse free
      radical-mediated reactions. Because of the unique reactivity of free radicals,
      radical SAM enzymes frequently catalyze chemically challenging reactions critical
      for the biosynthesis of unique structures of cofactors and natural products. In
      this Perspective, I will discuss the impact of characterizing novel functions in
      radical SAM enzymes on our understanding of biosynthetic pathways and use two
      recent examples from my own group with a particular emphasis on two radical SAM
      enzymes that are responsible for carbon skeleton formation during the
      biosynthesis of a cofactor and natural products.

PMID- 29072837
TI  - Dual-Channel, Molecular-Sieving Core/Shell ZIF@MOF Architectures as Engineered
      Fillers in Hybrid Membranes for Highly Selective CO2 Separation.
AB  - A novel core/shell porous crystalline structure was prepared using a large pore
      metal organic framework (MOF, UiO-66-NH2, pore size, ~ 0.6 nm) as core surrounded
      by a small pore zeolitic imidazolate framework (ZIF, ZIF-8, pore size, ~ 0.4 nm)
      through a layer-by-layer deposition method and subsequently used as an engineered
      filler to construct hybrid polysulfone (PSF) membranes for CO2 capture. Compared
      to traditional fillers utilizing only one type of porous material with rigid
      channels (either large or small), our custom designed core/shell fillers possess
      clear advantages via pore engineering: the large internal channels of the UiO-66
      NH2 MOFs create molecular highways to accelerate molecular transport through the
      membrane, while the thin shells with small pores (ZIF-8) or even smaller pores
      generated at the interface by the imperfect registry between the overlapping
      pores of ZIF and MOF enhance molecular sieving thus serving to distinguish
      slightly larger N2 molecules (kinetic diameter, 0.364 nm) from smaller CO2
      molecules (kinetic diameter, 0.33 nm). The resultant core/shell ZIF@MOF and as
      prepared hybrid PSF membranes were characterized by transmission electron
      microscopy, X-ray diffraction, wide-angle X-ray scattering, scanning electron
      microscopy, Fourier transform infrared, thermogravimetric analysis, differential
      scanning calorimetry, and contact angle tests. The dependence of the separation
      performance of the membranes on the MOF/ZIF ratio was also studied by varying the
      number of layers of ZIF coatings. The integrated PSF-ZIF@MOF hybrid membrane (40
      wt % loading) with optimized ZIF coating cycles showed improved hydrophobicity
      and excellent CO2 separation performance by simultaneously increasing CO2
      permeability (CO2 permeability of 45.2 barrer, 710% higher than PSF membrane) and
      CO2/N2 selectivity (CO2/N2 selectivity of 39, 50% higher than PSF membrane),
      which is superior to most reported hybrid PSF membranes. The strategy of using
      dual-channel molecular sieving core/shell porous crystals in hybrid membranes
      thus provides a promising means for CO2 capture from flue gas.

PMID- 29072838
TI  - Correction to Origins of Regioselectivity in the Fischer Indole Synthesis of a
      Selective Androgen Receptor Modulator.

PMID- 29072839
TI  - Observation of Vacancies, Faults, and Superstructures in Ln5Mo2O12 (Ln = La, Y,
      and Lu) Compounds with Direct Mo-Mo Bonding.
AB  - Among oxide compounds with direct metal-metal bonding, the Y5Mo2O12 (A5B2O12)
      structural family of compounds has a particularly intriguing low-dimensional
      structure due to the presence of bioctahedral B2O10 dimers arranged in one
      dimensional edge-sharing chains along the direction of the metal-metal bonds.
      Furthermore, these compounds can have a local magnetic moment due to the
      noninteger oxidation state (+4.5) of the transition metal, in contrast to the
      conspicuous lack of a local moment that is commonly observed when oxide compounds
      with direct metal-metal bonding have integer oxidation states resulting from the
      lifting of orbital degeneracy typically induced by the metal-metal bonding.
      Although a monoclinic C2/m structure has been previously proposed for Ln5Mo2O12
      (Ln = La-Lu and Y) members of this family based on prior single crystal
      diffraction data, it is found that this structural model misses many important
      structural features. On the basis of synchrotron powder diffraction data, it is
      shown that the C2/m monoclinic unit cell represents a superstructure relative to
      a previously unrecognized orthorhombic Immm subcell and that the superstructure
      derives from the ordering of interchangeable Mo2O10 and LaO6 building blocks. The
      superstructure for this reason is typically highly faulted, as evidenced by the
      increased breadth of superstructure diffraction peaks associated with a coherence
      length of 1-2 nm in the c* direction. Finally, it is shown that oxygen vacancies
      can occur when Ln = La, producing an oxygen deficient stoichiometry of
      La5Mo2O11.55 and an approximately 10-fold reduction in the number of unpaired
      electrons due to the reduction of the average Mo valence from +4.5 to +4.05, a
      result confirmed by magnetic susceptibility measurements. This represents the
      first observation of oxygen vacancies in this family of compounds and provides an
      important means of continuously tuning the magnetic interactions within the one
      dimensional octahedral chains of this system.

PMID- 29072841
TI  - Hypercapnic Pulmonary Vasoconstriction as a Mechanism for Regional Perfusion
      Redistribution in Asthma.

PMID- 29072842
TI  - Impact of Chronic Obstructive Pulmonary Disease on Immune-based Treatment for
      Lung Cancer. Moving toward Disease Interception.

PMID- 29072843
TI  - Literature Search and Review.

PMID- 29072840
TI  - MicroED Structure of Au146(p-MBA)57 at Subatomic Resolution Reveals a Twinned FCC
      Cluster.
AB  - Solving the atomic structure of metallic clusters is fundamental to understanding
      their optical, electronic, and chemical properties. Herein we present the
      structure of the largest aqueous gold cluster, Au146(p-MBA)57 (p-MBA: para
      mercaptobenzoic acid), solved by electron micro-diffraction (MicroED) to
      subatomic resolution (0.85 A) and by X-ray diffraction at atomic resolution (1.3
      A). The 146 gold atoms may be decomposed into two constituent sets consisting of
      119 core and 27 peripheral atoms. The core atoms are organized in a twinned FCC
      structure, whereas the surface gold atoms follow a C2 rotational symmetry about
      an axis bisecting the twinning plane. The protective layer of 57 p-MBAs fully
      encloses the cluster and comprises bridging, monomeric, and dimeric staple
      motifs. Au146(p-MBA)57 is the largest cluster observed exhibiting a bulk-like FCC
      structure as well as the smallest gold particle exhibiting a stacking fault.

PMID- 29072844
TI  - Advances in postharvest technologies to extend the storage life of minimally
      processed fruits and vegetables.
AB  - Minimally processed fresh produce is one of the fastest growing segments of the
      food industry due to consumer demand for fresh, healthy, and convenient foods.
      However, mechanical operations of cutting and peeling induce the liberation of
      cellular contents at the site of wounding that can promote the growth of
      pathogenic and spoilage microorganisms. In addition, rates of tissue senescence
      can be enhanced resulting in reduced storage life of fresh-cut fruits and
      vegetables. Chlorine has been widely adopted in the disinfection and washing
      procedures of fresh-cut produce due to its low cost and efficacy against a broad
      spectrum of microorganisms. Continuous replenishment of chlorine in high organic
      wash water can promote the formation of carcinogenic compounds such as
      trihalomethanes, which threaten human and environmental health. Alternative green
      and innovative chemical and physical postharvest treatments such as ozone,
      electrolyzed water, hydrogen peroxide, ultraviolet radiation, high pressure
      processing, and ultrasound can achieve similar reduction of microorganisms as
      chlorine without the production of harmful compounds or compromising the quality
      of fresh-cut produce.

PMID- 29072845
TI  - Hypercapnic Pulmonary Vasoconstriction Contributes to Regional Perfusion
      Distribution: Relevance to Asthma.

PMID- 29072846
TI  - Is There a TIME and Place for Thrombolytics in Malignant Pleural Effusions?

PMID- 29072847
TI  - The Man in the Paper Mask: One (Mask) for All and All for . . . Cystic Fibrosis?

PMID- 29072848
TI  - [Articles of the Hungarian Medical Journal from March, 2001].

PMID- 29072849
TI  - [Articles of the Hungarian Medical Journal from February, 2001].

PMID- 29072850
TI  - Reply to Dorrington et al. and to Swenson: "Hypercapnic Pulmonary
      Vasoconstriction Contributes to Regional Perfusion Distribution: Relevance to
      Asthma" and "Hypercapnic Pulmonary Vasoconstriction as a Mechanism for Regional
      Perfusion Redistribution in Asthma".

PMID- 29072851
TI  - Cervical cancer treated with reduced-volume intensity-modulated radiation therapy
      base on Sedlis criteria (NCCN VS RTOG).
AB  - OBJECTIVE: This study aimed to evaluate the clinical efficacy of different target
      volumes in pelvic radiotherapy in postoperative treatment of cervical cancer
      based on the Sedlis criteria. METHODS: Patients who admitted to our department
      for post-operative radiotherapy of cervical cancer from December 2001 to December
      2011 and met the Sedlis criteria were retrospectively analysed. The incidences of
      acute and late radiation injuries, and overall, disease-free and tumour-specific
      survival with reduced-volume pelvic and whole-pelvis radiotherapy were evaluated
      and compared. RESULTS: A total of 371 patients were included in the study,
      including 239 receiving whole-pelvis radiotherapy and 132 receiving reduced
      volume pelvic radiotherapy. The volume of contours for mean PTV volumes,
      bilateral femoral heads and small intestine volumes in reduced-volume pelvic
      radiotherapy were lower than whole-pelvis radiotherapy; the results were similar
      to the V10, V20, V30, V40 and V45 for pelvic bone marrow and small intestine dose
      volume (both p < 0.05). The acute radiation injury observed in the two groups was
      mainly haematologic toxicity and upper and lower gastrointestinal symptoms. The
      incidences of acute radiation injury, and late radiation injury of
      gastrointestinal and urinary tracts were both significantly lower with reduced
      volume pelvic radiotherapy than with whole-pelvis radiotherapy (both p < 0.05).
      Moreover, there was no significant difference in the incidence of lower extremity
      oedema, or 2-year or 5-year overall, disease-free or tumour-specific survival
      between groups (all p > 0.05). CONCLUSION: Reduced-volume pelvic radiotherapy
      could relieve acute and late radiation injuries, especially myelosuppression, and
      did not affect long-term survival. Advanced in knowledge: Our study shows that
      reduced-volume base on National Comprehensive Cancer Network 2016 is more fit for
      cervical cancer than others.

PMID- 29072852
TI  - The effect of Mepitel Film on acute radiation-induced skin reactions in head and
      neck cancer patients: a feasibility study.
AB  - OBJECTIVE: Mepitel Film significantly decreases acute radiation-induced skin
      reactions in breast cancer patients. Here we investigated the feasibility of
      using Mepitel Film in head and neck cancer patients (ACTRN12614000932662).
      METHODS: Out of a total of 36 head and neck cancer patients from New Zealand (NZ)
      (n = 24) and China (n = 12) recruited between June 2015 and December 2016, 33
      patients complied with protocol. Of these, 11 NZ patients followed a management
      protocol; 11 NZ patients and 11 Chinese patients followed a prophylactic
      protocol. An area of the neck receiving a homogenous radiation dose of > 35 Gy
      was divided into two equal halves; one half was randomized to Film and the other
      to either Sorbolene cream (NZ) or Biafine cream (China). Skin reaction severity
      was measured by Radiation Induced Skin Reaction Assessment Scale and expanded
      Radiation Therapy Oncology Group toxicity criteria. Skin dose was measured by
      thermoluminescent dosimeters or gafchromic film. RESULTS: Film decreased overall
      skin reaction severity (combined Radiation Induced Skin Reaction Assessment Scale
      score) by 29% and moist desquamation rates by 37% in the Chinese cohort and by 27
      and 28%, respectively in the NZ cohort. Mepitel Film did not affect head
      movements but did not adhere well to the skin, particularly in males with heavy
      beard stubble, and caused itchiness, particularly in Chinese patients.
      CONCLUSION: Mepitel Film reduced acute radiation-induced skin reactions in our
      head and neck cancer patients, particularly in patients without heavy stubble.
      Advances in knowledge: This is the first study to confirm the feasibility of
      using Mepitel Film in head and neck cancer patients.

PMID- 29072853
TI  - Dual-region-of-interest bolus-tracking technique for coronary computed
      tomographic angiography on a 320-row scanner: reduction in the interpatient
      variability of arterial contrast enhancement.
AB  - OBJECTIVE: We compared the effect of a dual-region-of-interest (ROI) bolus
      tracking technique on interpatient variability of arterial contrast enhancement
      with that of the conventional bolus-tracking technique in coronary computed
      tomographic angiography (CTA) on a 320-row scanner. METHODS: This study included
      100 patients who underwent coronary CTA using one of two protocols: (1) 50
      patients underwent scanning using a conventional single-ROI bolus-tracking
      technique (P-single) with an ROI placed in the ascending aorta, and (2) 50
      patients underwent scanning using a dual-ROI technique (P-dual) with two ROIs
      placed in the pulmonary trunk and the ascending aorta. CT attenuation in the
      ascending aorta and coronary arteries, and the interpatient variability were
      compared between the two scanning protocols. RESULTS: The mean CT attenuation of
      the ascending aorta and coronary arteries tended to be higher for P-dual than for
      P-single, but the difference was not significant (p = 0.08-0.30). The
      interpatient variability of contrast enhancement (SD of the CT attenuation) was
      significantly smaller for P-dual than for P-single (p < 0.01). CONCLUSION: The
      dual-ROI bolus-tracking technique can reduce interpatient variability of arterial
      contrast enhancement in coronary CTA on a 320-row scanner. Advances in knowledge:
      The use of a dual-ROI bolus-tracking technique can provide sufficient and
      consistent arterial enhancement of coronary CTA.

PMID- 29072854
TI  - Two-Year Stability and Change in Access to and Reasons for Lacking a Usual Source
      of Care Among Working-Age US Adults.
AB  - OBJECTIVE: The objective of this study was to investigate usual source of care
      (USC) over time. METHODS: A nationally representative sample of working-age
      adults in the Medical Expenditure Panel Survey (Panels 16 [2011-2012] and 17
      [2012-2013]) was divided into 3 groups based on USC questions asked during 2
      waves: (1) those having a USC during both waves (always USC), (2) those not
      having a USC during either wave (never USC), and (3) those who gained or lost a
      USC between the 2 waves (changed USC). The study examined the sociodemographic
      and health characteristics associated with these groups and the main reasons for
      not having a USC among those who never had a USC and those who changed their USC.
      RESULTS: Of the 10 792 adults in the analysis, a longitudinally weighted 18.8%
      reported that their USC changed during the period. Among adults in the changed
      USC group, those with private (odds ratio [OR] = 2.0, P = .001) or public (OR =
      2.2, P = .001) health insurance and 1 (OR = 1.7, P = .04) or >=2 (OR = 3.1, P =
      .02) chronic health conditions were more likely to transition to having a USC
      from not having a USC, compared with those who had no insurance and no chronic
      conditions. Compared with those in the changed USC group, those in the never USC
      group were more likely to report preferring not to have a USC (57.9% vs 80.1%, P
      < .001). CONCLUSIONS: Insurance and public health policies and programs are
      needed to reduce short-term changes in USC and increase the number of adults with
      ongoing, consistent USC.

PMID- 29072855
TI  - Francois Leuret: the last moral therapist.
AB  - By the 1840s French psychiatrists had abandoned Moral Treatment as an individual
      psychological therapy, as opposed to an institutional practice. One advocate of
      Moral Treatment, however, would not go along with this movement. In three books
      and several papers published between 1834 and 1846, Francois Leuret (1797-1851)
      advocated aggressive psychological treatment. Recent commentators have
      understandably concentrated on the controversies surrounding Leuret's practices.
      What such an approach has failed to make clear, however, is that Leuret had a
      complex, systematic psychological theory supporting his clinical judgements. In
      addition to reviewing the controversies that surrounded Leuret, this paper spells
      out Leuret's psychological theory and shows how he used this theory to think
      about the individual psychotherapy he provided for his patients.

PMID- 29072856
TI  - Sex differences in estimated brain metabolism in relation to body growth through
      adolescence.
AB  - The human brain consumes a disproportionate amount of the body's overall
      metabolic resources, and evidence suggests that brain and body may compete for
      substrate during development. Using perfusion MRI from a large cross-sectional
      cohort, we examined developmental changes of MRI-derived estimates of brain
      metabolism, in relation to weight change. Nonlinear models demonstrated that, in
      childhood, changes in body weight were inversely related to developmental age
      related changes in brain metabolism. This inverse relationship persisted through
      early adolescence, after which body and brain metabolism began to decline.
      Females achieved maximum body growth approximately two years earlier than males,
      with a correspondingly earlier stabilization of brain metabolism to adult levels.
      These findings confirm prior findings with positron emission tomography performed
      in a much smaller cohort, demonstrate that relative brain metabolism can be
      inferred from noninvasive MRI data, and extend observations on the associations
      between body growth and brain metabolism to sex differences through adolescence.

PMID- 29072857
TI  - Astrocytes drive cortical vasodilatory signaling by activating endothelial NMDA
      receptors.
AB  - Astrocytes express neurotransmitter receptors that serve as sensors of synaptic
      activity and initiate signals leading to activity-dependent local vasodilation
      and increases in blood flow. We previously showed that arteriolar vasodilation
      produced by activation of cortical astrocytes is dependent on endothelial nitric
      oxide synthase (eNOS) and endogenous agonists of N-methyl-D-aspartate (NMDA)
      receptors. Here, we tested the hypothesis that these effects are mediated by NMDA
      receptors expressed by brain endothelial cells. Primary endothelial cultures
      expressed NMDA receptor subunits and produced nitric oxide in response to co
      agonists, glutamate and D-serine. In cerebral cortex in situ, immunoelectron
      microscopy revealed that endothelial cells express the GluN1 NMDA receptor
      subunit at basolateral membrane surfaces in an orientation suitable for receiving
      intercellular messengers from brain cells. In cortical slices, activation of
      astrocytes by two-photon flash photolysis of a caged Ca2+ compound or application
      of a metabotropic glutamate receptor agonist caused endothelial NO generation and
      local vasodilation. These effects were mitigated by NMDA receptor antagonists and
      conditional gene silencing of endothelial GluN1, indicating at least partial
      dependence on endothelial NMDA receptors. Our observations identify a novel
      astrocyte-endothelial vasodilatory signaling axis that could contribute to
      endothelium-dependent vasodilation in brain functional hyperemia.

PMID- 29072859
TI  - Correlation between periodontal soft tissue and hard tissue surrounding incisors
      in skeletal Class III patients.
AB  - OBJECTIVES: To investigate the association between the periodontal soft tissue,
      alveolar bone and dental parameters surrounding the incisors at baseline in
      patients with skeletal Class III malocclusion. MATERIALS AND METHODS: The study
      sample comprised 154 teeth from 28 patients with skeletal Class III malocclusion
      (19 men and 9 women, 21.15 +/- 4.02 years). Periodontal soft tissue examination
      and hard tissue measurements with cone-beam computed tomography (CBCT) were
      performed. Factor analysis was used to reduce the CBCT variables, and correlation
      analysis between the hard tissue factors and soft tissue parameters was
      performed. Differences in hard tissue parameters between thick and thin gingival
      types were evaluated. RESULTS: CBCT measurements were reduced to three hard
      tissue factors: lingual plate, coronal-buccal plate, and apical-buccal plate.
      Keratinized gingiva width and thickness were positively correlated with the
      coronal-buccal plate factor and negatively correlated with the apical-buccal
      plate factor. In the thin gingival biotype, mandibular incisors were more
      proclined, and the apical part of the buccal alveolar plate and the coronal part
      of lingual alveolar plate were thicker than in the thick gingival biotype.
      CONCLUSIONS: In the anterior teeth in cases of skeletal Class III malocclusion,
      hard tissue structures on the buccal side can be grouped based on coronal and
      apical factors that are significantly correlated with keratinized gingival width
      and thickness. Thick and thin gingival biotypes exhibited differences in tooth
      inclination and alveolar plate thickness with regard to the mandibular incisors.

PMID- 29072860
TI  - Clinical Profile of Herpes Zoster Ophthalmicus in a South Indian Patient
      Population.
AB  - PURPOSE: To analyze and compare the clinical profile of herpes zoster
      ophthalmicus (HZO) patients in a South Indian patient population aged <60 years
      and >=60 years and determine the risk factors for recurrence of ocular
      inflammation. METHODS: Retrospective study of 249 cases between 2006 and 2016
      from two tertiary referral eye centres in south india. RESULTS: Out of 249 cases,
      189 cases were <60 years (Group 1) and 60 cases were aged >=60 years (Group2).
      Presence of diabetes mellitus, increased intraocular pressure(IOP) at the time of
      active inflammation, use of topical steroids and recurrences were significantly
      more common in group 1. Significant risk factors for recurrences included
      corneal, uveal, scleral involvements and increase in IOP. Good vision at
      presentation was noted in 67.9% of the patients. CONCLUSIONS: Anterior uveitis
      with or without keratitis was the most common presentation observed in more than
      50% cases. The overall visual outcome was good.

PMID- 29072858
TI  - Flat epithelial atypia: conservative management of patients without residual
      microcalcifications post-vacuum-assisted breast biopsy.
AB  - OBJECTIVE: To determine the malignancy rate (defined in this study as stability
      or absence of malignancy developed on close imaging follow-up post-biopsy) of
      conservative management in patients with a vacuum-assisted breast biopsy (VAB)
      diagnosis of flat epithelial atypia (FEA), performed on single group of
      microcalcifications, completely removed during procedure. METHODS: This is a
      retrospective, monocentric, observational study, approved by IRB. Inclusion
      criteria were: VAB performed on a single group of microcalcifications; the
      absence of residual calcifications post-VAB; diagnosis of isolated FEA as the
      most advanced proliferative lesion; radiological follow-up at least of 12 months.
      The personal history of breast cancer or other high-risk lesions was an exclusion
      criteria. The patients enrolled were conservatively managed, without surgical
      excision, through close follow-up: the first two mammographies performed with an
      interval of 6 months after biopsy, followed by annual mammographic and clinical
      checks. RESULTS: 48 consecutive patients were enrolled in the study, all females,
      with age range of 39-76 years (mean 53,3 years) and radiological follow-up range
      of 13-75 months (mean 41.5 months). All the lesions were classified as BI-RADS
      4b. The diameter range of the group of calcifications was 3-10 mm (mean 5, 6 mm).
      In each patient, 7 to 15 samples (mean 11) were obtained. Among all the patients,
      there was only one case (2%) of new microcalcifications, developed in the same
      breast, 26 months after and 8 mm from the site of previous VAB, and interpreted
      as ADH at surgical excision. All the checks of the other patients were negative.
      CONCLUSION: Even with a limited follow-up, we found a malignancy rate lower than
      2%, through a defined population. Further studies with bigger number of patients
      and extended follow-up are needed to reinforce this hypothesis. Advances in
      knowledge: Surgical excision may not be necessary in patients with VAB diagnosis
      of isolated FEA, without residual microcalcifications post-procedure and
      considered concordant with the mammographic presentation, considering the low
      rate of malignancy at subsequent follow-ups.

PMID- 29072861
TI  - The Effect of Low-Level Laser Therapy on Bone Healing After Rapid Maxillary
      Expansion: A Systematic Review.
AB  - OBJECTIVE: The study aimed to systematically appraise the evidence on the effects
      of low level laser therapy (LLLT) on bone healing following rapid maxillary
      expansion (RME). METHODS: Electronic search was performed in MEDLINE, Scopus, and
      Embase databases using appropriate Medical Subject Heading terms, with no time
      restriction. ClinicalTrials.gov ( www.clinicaltrials.gov ) was also searched
      using the terms "low level laser therapy" and "maxillary expansion." SELECTION
      CRITERIA: Original research articles on human clinical trials that involved both
      RME and LLLT were included. Animal studies were also assessed on an exploratory
      basis. RESULTS: The search strategy resulted in 12 publications (4 randomized
      controlled trials, 8 animal studies). In human studies, bone density was assessed
      radiographically (either two-dimensional or three-dimensional imaging).
      Regardless of the discrepancies in the intervention protocols, the total of the
      trials revealed that LLLT had stimulatory effects on bone regeneration after RME.
      The studies in animal models measured the formation and maturation of new bone
      qualitatively or quantitatively. CONCLUSIONS: Despite the limited evidence, LLLT
      seems to be a promising intervention for stimulating immediate bone regeneration
      and healing after midpalatal suture expansion. Long-term, randomized clinical
      trials are needed to formulate safe results and establish a reliable clinical
      protocol, rendering the method clinically applicable.

PMID- 29072862
TI  - Lymph Drainage from the Chylocyst-Induced Hemodilution in an In Vivo Rabbit
      Study.
AB  - To confirm our previous study that abdominal respiration has induced hemodilution
      in human subjects, we performed in-vivo experiments involving anesthetized
      rabbits. Fifteen 6- to 7-month-old male Japanese white rabbits were used in the
      animal experiments. Anesthesia was maintained with 2.5%-3.0% isoflurane under N2O
      + 100% O2 inhalation. Ventilation was maintained at 40 mL/breath for 20
      breaths/min. Physiological saline solution was administered at rated 18 mL/h
      during the experiments. First, we attempted to evaluate lymph flow through the
      thoracic duct using Sonazoid-based contrast-enhanced ultrasound (CEUS)-guided
      method and then investigated the effects of manual lymph drainage of the
      chylocyst on the numbers of red blood cells (RBC), hematocrit (Ht) levels, and
      the blood concentrations of total protein (TP) and hemoglobin (Hb). In this
      study, we established surgical methods for identifying the left venous angle and
      chylocyst using Evans blue dye in anesthetized rabbits. We also confirmed that a
      Sonazoid-based CEUS-guided method was the most useful technique for producing
      real-time images of lymph flow through the thoracic duct in anesthetized rabbits.
      In addition, in present experiments involving anesthetized rabbits, we confirmed
      that manually massaging the chylocyst produced significant hemodilution. Thus,
      the procedure produced significant reductions of TP, RBC, Hb, and Ht level in the
      rabbits.

PMID- 29072863
TI  - Timeliness of Receipt of Early Childhood Vaccinations Among Children of
      Immigrants - Minnesota, 2016.
AB  - Receiving recommended childhood vaccinations on schedule is the best way to
      prevent the occurrence and spread of vaccine-preventable diseases (1).
      Vaccination coverage among children aged 19-35 months in the United States
      exceeds 90% for most recommended vaccines in the early childhood series (2);
      however, previous studies have found that few children receive all recommended
      vaccine doses on time (3). The Minnesota Department of Health (MDH), using
      information from the Minnesota Immunization Information Connection (MIIC) and the
      MDH Office of Vital Records, examined early childhood immunization rates and
      found that children with at least one foreign-born parent were less likely to be
      up-to-date on recommended immunizations at ages 2, 6, 18, and 36 months than were
      children with two U.S.-born parents. Vaccination coverage at age 36 months varied
      by mother's region of origin, ranging from 77.5% among children born to mothers
      from Central and South America and the Caribbean to 44.2% among children born to
      mothers from Somalia. Low vaccination coverage in these communities puts
      susceptible children and adults at risk for outbreaks of vaccine-preventable
      diseases, as evidenced by the recent measles outbreak in Minnesota (4). Increased
      outreach to immigrant, migrant, and refugee populations and other populations
      with low up-to-date vaccination rates might improve timely vaccination in these
      communities.

PMID- 29072865
TI  - Tobacco Use Among Working Adults - United States, 2014-2016.
AB  - Cigarette smoking has declined considerably among U.S. adults over several
      decades (1); however, increases have occurred in the use of noncigarette tobacco
      products in recent years, and the use of multiple tobacco products has become
      common among current users of noncigarette tobacco products (2,3). Differences in
      tobacco use have also been observed across population subgroups, including among
      working adults (2,4). CDC analyzed National Health Interview Survey (NHIS) data
      for 2014-2016 to describe the most recent prevalence estimates of current (every
      day or some days) tobacco product use among working U.S. adults by industry and
      occupation. Among working adults, 22.1% (32.7 million) currently used any form of
      tobacco; 15.4% used cigarettes, 5.8% used other combustible tobacco (cigars,
      pipes, water pipes or hookahs, very small cigars, and bidis), 3.0% used smokeless
      tobacco, and 3.6% used electronic cigarettes (e-cigarettes); 4.6% (6.9 million)
      reported current use of two or more tobacco products. By industry, any tobacco
      use ranged from 11.0% among education services to 34.3% among construction
      workers; current use of two or more tobacco products was highest among
      construction workers (7.1%). By occupation, any tobacco use ranged from 9.3%
      among life, physical, and social science workers to 37.2% among installation,
      maintenance, and repair workers; current use of two or more tobacco products was
      highest among installation, maintenance, and repair workers (10.1%). Proven
      interventions to prevent and reduce tobacco product use, including current use of
      multiple products, among working adults are important (5,6). Workplace tobacco
      control interventions have been especially effective in reducing cigarette
      smoking prevalence (7).

PMID- 29072864
TI  - Increased Risk for Mother-to-Infant Transmission of Hepatitis C Virus Among
      Medicaid Recipients - Wisconsin, 2011-2015.
AB  - State surveillance during the last 10 years reveals a nationwide increase in
      hepatitis C virus (HCV) infection among young adults (1). The proportion of
      infants born to HCV-infected women is also increasing nationally (2). To estimate
      the proportion of infants born to HCV-infected women and the frequency of
      confirmed HCV infection in their infants, maternal name and date of birth from
      HCV reports in the Wisconsin Electronic Disease Surveillance System (WEDSS) were
      linked to Wisconsin Medicaid data for 2011-2015 births. During this period, in
      the Wisconsin Medicaid population, the proportion of women who had evidence of
      HCV infection during pregnancy increased 93%, from 1 in 368 pregnancies to 1 in
      192. Among 183 infants born to women with evidence of HCV viremia during
      pregnancy, 34% received recommended HCV testing (3). Mother-to-infant (vertical)
      transmission was documented in 4% of infants. Improvements in HCV screening
      practices among pregnant women and infants could enhance identification of
      infants at risk for vertical transmission of HCV.

PMID- 29072866
TI  - Maternal educational status at birth, maternal educational advancement, and
      neurocognitive outcomes at age 10 years among children born extremely preterm.
AB  - BackgroundTo determine if a key marker of socioeconomic status, maternal
      education, is associated with later neurocognitive and academic outcomes among
      children born extremely preterm (EP).MethodEight hundred and seventy-three
      children born at 23 to 27 weeks of gestation were assessed for cognitive and
      academic ability at age 10 years. With adjustments for gestational age (GA) and
      potential confounders, outcomes of children whose mothers had fewer years of
      education at the time of delivery and children whose mother advanced in education
      between birth and 10 years were examined.ResultsChildren of mothers in the lowest
      education stratum at birth were significantly more likely to score >=2 SDs below
      normative expectation on 17 of 18 tests administered. Children of mothers who
      advanced in education (n=199) were at reduced risk for scoring >=2 SDs on 15 of
      18 measures, but this reduction was statistically significant on only 2 of 18
      measures.ConclusionAmong EP children, socioeconomic disadvantage at birth,
      indexed by maternal education, is associated with significantly poorer
      neurocognitive and academic outcomes at 10 years of age, independently of GA.
      Maternal educational advancement during the child's first 10 years of life is
      associated with modestly improved neurocognitive outcomes.

PMID- 29072867
TI  - Measuring impact of telephone triage in Acute Medicine.
AB  - The Society for Acute Medicine's Benchmarking Audit (SAMBA) was undertaken for
      the 5th time in June 2016. For the first time, data on telephone triage calls
      prior to admission to Acute Medical Units were collected: 1238 patients were
      referred from Emergency Departments, 925 from General Practitioners (GPs), 52
      from clinics and 147 from other sources. Calls from Emergency Departments rarely
      resulted in admission avoidance. Calls from Primary Care resulted in avoidance of
      an admission in 115 (12%) patients; the percentage of avoided admissions was
      highest if the call was taken by a Consultant. Consultant triage might result in
      admission avoidance but the impact of local context on the effectiveness is not
      clear.

PMID- 29072868
TI  - Electronic Prompts Can Reduce The Number Of Unnecessary Clotting Screens Ordered
      For Patients.
AB  - In an attempt to reduce the number of inappropriate clotting screens being
      performed in our Trust, an electronic prompt was introduced to our haematology
      requesting system. Over the six month period after introduction of this prompt
      the number of clotting screen requests reduced by 7001, representing a 21%
      reduction when compared to the same 6 month period one year earlier. This
      represented a cost saving of over L98,000 without any increase in adverse
      incidents being reported related to bleeding complications.

PMID- 29072869
TI  - Research Protocol: Intravenous Access during Resuscitation: the IVAR trial.
AB  - OBJECTIVE: To compare the effects of central versus peripheral drug
      administration on the rate of return of organised electrical activity and/or
      spontaneous circulation during CPR. STUDY DESIGN: Randomized clinical trial.
      STUDY POPULATION: Hospitalized patients and patients presenting at the emergency
      department, older than 18 years, requiring CPR. INTERVENTION: Central venous
      access Main study parameters/endpoints: Combined primary endpoint: rate of
      appearance of organised electrical activity or return of spontaneous circulation.
      Nature and extent of the burden and risks associated with participation, benefit
      and group relatedness: All patients are treated according to the guidelines of
      the European Resuscitation Council, which are endorsed by the local VUMC CPR
      committee. Central access will be obtained by cannulation of the external or
      internal jugular vein. To avoid interference with initial management, central
      venous access will be obtained after initiation of chest compressions, first
      attempt at defibrillation (if applicable), securing the airway and obtaining a
      peripheral access. All resuscitated patients require vascular access and almost
      all successfully resuscitated patients require central venous access. Obtaining
      central access during CPR may be associated with a slightly higher complication
      rate, such as arterial puncture and pneumothorax. Possible benefits for study
      subjects are a higher success rate of CPR.

PMID- 29072870
TI  - Medical High Dependency Unit series, Article 3: Respiratory Support in the MHDU.
AB  - Acute respiratory failure is a life threatening condition encountered by Acute
      Physicians; additional non-invasive support can be provided within the medical
      high dependency unit (MHDU). Acute Physicians should strive to be experts in the
      investigation, management and support of patients with acute severe respiratory
      failure. This article outlines key management principles in these areas and
      explores common pitfalls.

PMID- 29072871
TI  - Disseminated intravascular coagulation in an under-recognised zoonotic infection.
AB  - A 51 year old man presented with severe sepsis, disseminated intravascular
      coagulation (DIC) and multiorgan dysfunction after a 24 hour history of diarrhoea
      and malaise. Despite fluid resuscitation and receiving a platelet transfusion,
      freshfrozen plasma and intravenous broad-spectrum antibiotics, he remained anuric
      with a worsening metabolic acidosis. He was transferred to critical care for
      organ support including renal replacement therapy. He subsequently developed
      purpura fulminans. Blood cultures were positive for Captocytophaga carnimorsis, a
      gram-negative canine zoonosis that is an underdiagnosed cause of severe sepsis,
      for which DIC at presentation is characteristic. Treatment is with penicillins
      and fluoroquinolones. Identification of risk factors for unusual organisms and
      recognition of DIC allowing prompt treatment is critical for the acute physician.

PMID- 29072872
TI  - Third cranial nerve palsy: an unusual manifestation of Mycoplasma pneumoniae.
AB  - Mycoplasma Pneumoniae (M.pneumoniae) is a well-known cause of atypical pneumonia,
      however it is also associated with many extra pulmonary manifestations. This
      report highlights a patient with gastroenterological, haematological and
      neurological complications, including a third cranial nerve palsy which developed
      after her initial treatment and discharge from hospital.

PMID- 29072873
TI  - Not just a simple sore throat.
AB  - The presentation of a 'sore throat' is common and often requires only symptomatic
      treatment. This is the case of a 20-year-old female who presented with persistent
      symptoms of a sore throat. On admission she had raised inflammatory markers and a
      subsequent blood culture demonstrated a fusobacterium necrophorum and
      arcanobacterium haemolyticum bacteraemia. Further investigations established an
      internal jugular vein thrombosis, confirming the diagnosis of Lemierre's
      syndrome. This case highlights the importance of further investigation when a
      sore throat fails to improve, and to remember this often-forgotten syndrome.

PMID- 29072874
TI  - Society for Acute Medicine Trainee Update, Autumn 2017.
AB  - Tehmeena Khan has replaced Sanjay Krishnamoorthy as a Trainee Representative for
      SAM. We would like to thank Sanjay for all his hard work and contribution during
      his tenure as Rep. Tehmeena is a final year trainee from North East & Central
      London. Tehmeena's specialist skills are Leadership, Management and Quality
      Improvement. She has previously been a Darzi Fellow and has undertaken a Winston
      Churchill Fellowship. She has recently joined the Health Foundation Q Community.

PMID- 29072875
TI  - Oxford specialist handbooks in neurology: Stroke Medicine.
AB  - This is a pocket sized book (if your pockets are 20*18*2 cm big, that is) and it
      weighs less than two decent stethoscopes. Its small physical size belies the
      comprehensive coverage given to the subject. It is a really a compact textbook
      covering all aspects of stroke care.

PMID- 29072876
TI  - Identification of Glyceraldehyde-3-Phosphate and Alcohol Dehydrogenases as
      Autoantigens in Doberman Hepatitis.
AB  - An autoimmune background is suspected for Doberman hepatitis (DH). It is based on
      the finding of mononuclear cell infiltrates in the liver, strong female bias,
      association to the homozygous risk factor dog leucocyte antigen (DLA) allele
      DRB1*00601 and aberrant major histocompatibility complex (MHC) class II
      expression on hepatocytes that correlates with the degree of inflammation in the
      liver. The aim of this study was to search for autoantibodies against liver
      related antigens associated with DH. Twenty-five Dobermans with subclinical DH
      (SDH), 13 that clinically manifest DH (CDH) and 17 healthy controls were studied.
      Immunoblotting analysis detected specific antibodies in the DH sera. By mass
      spectrometry the targets were identified as liver-related enzymes glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) and alcohol dehydrogenase (ADH). Using ELISA,
      anti-GAPDH IgG was detected in 36% (9/25) of SDH dogs and 69.2% (9/13) of the CDH
      dogs compared to healthy controls (0/17) (P < 0.0005). Anti-ADH IgG was detected
      in 72% (18/25) of SDH dogs and 76.9% (10/13) of CDH dogs and only in one (1/17)
      control (P < 0.0005). The finding of novel autoantigens, GAPDH and ADH strengthen
      the hypothesis that DH is an autoimmune disease of the liver. These findings
      suggest that DH could be diagnosed by screening for autoantibodies against the
      defined antigens.

PMID- 29072877
TI  - A RhABF2/Ferritin module affects rose (Rosa hybrida) petal dehydration tolerance
      and senescence by modulating iron levels.
AB  - Plants often develop the capacity to tolerate moderate and reversible
      environmental stresses, such as drought, and to re-establish normal development
      once the stress has been removed. An example of this phenomenon is provided by
      cut rose (Rosa hybrida) flowers, which experience typical reversible dehydration
      stresses during post-harvest handling after harvesting at the bud stages. The
      molecular mechanisms involved in rose flower dehydration tolerance are not known,
      however. Here, we characterized a dehydration- and abscisic acid (ABA)-induced
      ferritin gene (RhFer1). Dehydration-induced free ferrous iron (Fe2+ ) is
      preferentially sequestered by RhFer1 and not transported outside of the petal
      cells, to restrict oxidative stresses during dehydration. Free Fe2+ accumulation
      resulted in more serious oxidative stresses and the induction of genes encoding
      antioxidant enzyme in RhFer1-silenced petals, and poorer dehydration tolerance
      was observed compared with tobacco rattle virus (TRV) controls. We also
      determined that RhABF2, an AREB/ABF transcription factor involved in the ABA
      signaling pathway, can activate RhFer1 expression by directly binding to its
      promoter. The silencing of RhABF2 decreased dehydration tolerance and disrupted
      Fe homeostasis in rose petals during dehydration, as did the silencing of RhFer1.
      Although both RhFer1 and Fe transporter genes are induced during flower natural
      senescence in plants, the silencing of RhABF2 or RhFer1 accelerates the petal
      senescence processes. These results suggest that the regulatory module
      RhABF2/RhFer1 contributes to the maintenance of Fe levels and enhances
      dehydration tolerance through the action of RhFer1 locally sequestering free Fe2+
      under dehydration conditions, and plays synergistic roles with transporter genes
      during flower senescence.

PMID- 29072878
TI  - Predictors of intimate partner violence among pregnant women.
AB  - OBJECTIVE: To identify predictive factors of intimate partner violence (IPV)
      among pregnant women. METHODS: In a cross-sectional study, 250 pregnant, married
      women attending three women's hospitals in South Korea for prenatal care were
      enrolled between July 1 and August 31, 2016. The women answered structured
      questionnaires assessing conflict negotiation coping, social support, and IPV,
      which was measured by 18 questions in three domains: psychological, physical, and
      sexual violence. Participants who reported experience in response to more than
      one question were deemed to have encountered IPV. Binomial logistic regression
      analysis was used to investigate predictive factors of IPV. RESULTS: Overall, 85
      (34.0%) participants had experienced IPV. Likelihood of IPV was linked with
      younger age (adjusted odds ratio [aOR] 0.90, 95% confidence interval [CI] 0.83
      0.94; P=0.012), unemployment (aOR 1.98, 95% CI 1.07-3.70; P=0.031), and graduate
      school education (aOR 7.32, 95% CI 1.68-31.84; P=0.008). The likelihood of IPV
      increased as the social support score decreased (aOR 0.92, 95% CI 0.88-0.95;
      P<0.001). CONCLUSION: Efforts to screen for IPV and to intervene to reduce the
      impact of such violence on pregnant women's delivery outcomes should be a
      maternal health priority in South Korea.

PMID- 29072879
TI  - Cockroach is a major cross-reactive allergen source in shrimp-sensitized rural
      children in southern China.
AB  - BACKGROUND: Little is known about the prevalence of food allergy (FA) in China.
      The aim of this study was to investigate the disparity of FA between urban and
      rural areas in southern China. METHODS: EuroPrevall questionnaire responses were
      obtained from 5542 school-age children in urban Guangzhou and 5319 in rural
      Shaoguan. A case-control study enrolled 190 children with adverse reactions (ARs)
      after food intake as cases and 212 controls in Guangzhou, whereas 116 cases and
      233 controls in Shaoguan. These subjects underwent skin prick test (SPT) and
      serum IgE measurements to food and inhalant allergens. Allergen extracts from
      shrimp, house dust mite (HDM), and cockroach were prepared for IgE cross
      reactivity testing in 23 Guangzhou and 20 Shaoguan shrimp-sensitized subjects.
      RESULTS: The prevalence of ARs to shrimp was higher in Guangzhou than in Shaoguan
      children (3.5% vs 1.4%, P < .001). However, sensitization rate to shrimp (SPT:
      3.7% vs 11.2%, P = .015; IgE: 12.6% vs 36.2%, P < .001) and cockroach (SPT: 5.3%
      vs 33.5%; IgE: 2.6% vs 27.6%, P < .001) was lower in Guangzhou. A significant
      correlation between shrimp and HDM/cockroach IgE was found in Shaoguan children.
      The proportions of positive IgE to tropomyosin (Pen a 1, Der p 10) were lower
      than 7.4% in both areas. Cockroach allergen has a significantly higher inhibition
      rate of binding to IgE to house dust mite allergens in Shaoguan sera. CONCLUSION:
      Shrimp is a common allergic food in southern China. Higher proportion of shrimp
      sensitization in rural subjects could be explained by cross-reactivity to
      cockroach. Tropomyosin was not a major allergen responding to the cross
      reactivity.

PMID- 29072880
TI  - Construction of Large-Area Uniform Graphdiyne Film for High-Performance Lithium
      Ion Batteries.
AB  - Large-area graphdiyne film is constructed by heat treatment, including thermally
      induced evaporation and a cross-coupling reaction process. The growth mechanism
      is proposed based on the observation and characterization that the heating
      temperature plays an important role in the evaporation of oligomers and in
      triggering the thermal cross-coupling reaction, whereas the heating duration
      mainly determines the execution of the thermal cross-coupling reaction. By
      controlling the heat-treatment process, a graphdiyne film with uniform morphology
      and good conductivity is obtained. The improved GDY film based electrodes deliver
      good interfacial contact and more lithium storage sites; thus leading to superior
      electrochemical performance. A reversible capacity of 901 mAh g-1 is achieved.
      Specifically, the electrodes exhibit excellent rate performance, with which a
      capacity of 430 mAh g-1 is maintained at a rate as high as 5 A g-1 . These
      advantages mean that the uniform graphdiyne film is a good candidate for the
      fabrication of a flexible and high-capacity electrode material.

PMID- 29072881
TI  - Case report of treatment with a sigmoid neovagina for a patient with
      vesicovaginal fistula and gynatresia.

PMID- 29072882
TI  - RItA: The Italian severe/uncontrolled asthma registry.
AB  - BACKGROUND: The Italian severe/uncontrolled asthma (SUA) web-based registry
      encompasses demographic, clinical, functional, and inflammatory data; it aims to
      raise SUA awareness, identifying specific phenotypes and promoting optimal care.
      METHODS: Four hundred and ninety three adult patients from 27 Italian centers
      (recruited in 2011-2014) were analyzed. RESULTS: Mean age was 53.8 years. SUA
      patients were more frequently female (60.6%), with allergic asthma (83.1%). About
      30% showed late onset of asthma diagnosis/symptoms (>40 years); the mean age for
      asthma symptoms onset was 30.2 years and for asthma diagnosis 34.4 years. 97.1%
      used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1%
      anti-IgE, 10.7% theophylline, and 16.0% oral corticosteroids. Mean FEV1 % pred of
      75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/L of serum
      total IgE, and 24 ppb of FENO were shown. Most common comorbidities were allergic
      rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal
      polyposis (30.2%), and allergic conjunctivitis (30.2%). 55.7% of SUA patients had
      exacerbations in the last 12 months, 9.7% emergency department visits, and 7.3%
      hospitalizations. Factors associated with exacerbation risk were obesity (OR, 95%
      CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30-borderline), nasal polyps
      (1.86, 0.88-3.89-borderline), partial/poor asthma treatment adherence (2.54, 0.97
      6.67-borderline), and anti-IgE use in a protective way (0.26, 0.12-0.53).
      Comparisons to severe asthma multicenter studies and available registries showed
      data consistency across European and American populations. CONCLUSIONS: An
      international effort in the implementation of SUA patients' registries could help
      to better understand the clinical features and to manage severe asthma,
      representing a non-negligible socioeconomic burden for health services.

PMID- 29072883
TI  - Highly interwoven communities of a gene regulatory network unveil topologically
      important genes for maize seed development.
AB  - The complex interactions between transcription factors (TFs) and their target
      genes in a spatially and temporally specific manner are crucial to all cellular
      processes. Reconstruction of gene regulatory networks (GRNs) from gene expression
      profiles can help to decipher TF-gene regulations in a variety of contexts;
      however, the inevitable prediction errors of GRNs hinder optimal data mining of
      RNA-Seq transcriptome profiles. Here we perform an integrative study of Zea mays
      (maize) seed development in order to identify key genes in a complex
      developmental process. First, we reverse engineered a GRN from 78 maize seed
      transcriptome profiles. Then, we studied collective gene interaction patterns and
      uncovered highly interwoven network communities as the building blocks of the
      GRN. One community, composed of mostly unknown genes interacting with opaque2,
      brittle endosperm1 and shrunken2, contributes to seed phenotypes. Another
      community, composed mostly of genes expressed in the basal endosperm transfer
      layer, is responsible for nutrient transport. We further integrated our inferred
      GRN with gene expression patterns in different seed compartments and at various
      developmental stages and pathways. The integration facilitated a biological
      interpretation of the GRN. Our yeast one-hybrid assays verified six out of eight
      TF-promoter bindings in the reconstructed GRN. This study identified
      topologically important genes in interwoven network communities that may be
      crucial to maize seed development.

PMID- 29072884
TI  - Only some questions of cause and effect can be evaluated in highly selected
      populations.

PMID- 29072885
TI  - Cardiopulmonary ultrasound for critically ill adults improves diagnostic accuracy
      in a resource-limited setting: the AFRICA trial.
AB  - OBJECTIVE: To assess the effects of a cardiopulmonary ultrasound (CPUS)
      examination on diagnostic accuracy for critically ill patients in a resource
      limited setting. METHODS: Approximately half of the emergency medicine resident
      physicians at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana, were
      trained in a CPUS protocol. Adult patients triaged to the resuscitation area of
      the emergency department (ED) were enrolled if they exhibited signs or symptoms
      of shock or respiratory distress. Patients were assigned to the intervention
      group if their treating physician had completed the CPUS training. The
      physician's initial diagnostic impression was recorded immediately after the
      history and physical examination in the control group, and after an added CPUS
      examination in the intervention group. This was compared to a standardised final
      diagnosis derived from post hoc chart review of the patient's care at 24 h by two
      blinded, independent reviewers using a clearly defined and systematic process.
      Secondary outcomes were 24-h mortality and use of IV fluids, diuretics,
      vasopressors and bronchodilators. RESULTS: Of 890 patients presenting during the
      study period, 502 were assessed for eligibility, and 180 patients were enrolled.
      Diagnostic accuracy was higher for patients who received the CPUS examination
      (71.9% vs. 57.1%, Delta 14.8% [CI 0.5%, 28.4%]). This effect was particularly
      pronounced for patients with a 'cardiac' diagnosis, such as cardiogenic shock,
      congestive heart failure or acute valvular disease (94.7% vs. 40.0%, Delta 54.7%
      [CI 8.9%, 86.4%]). Secondary outcomes were not different between groups.
      CONCLUSIONS: In an urban ED in Ghana, a CPUS examination improved the accuracy of
      the treating physician's initial diagnostic impression. There were no differences
      in 24-h mortality and a number of patient care interventions.

PMID- 29072887
TI  - Axiomatic Design of a Framework for the Comprehensive Optimization of Patient
      Flows in Hospitals
AB  - Lean Management and Six Sigma are nowadays applied not only to the manufacturing
      industry but also to service industry and public administration. The manifold
      variables affecting the Health Care system minimize the effect of a narrow Lean
      intervention. Therefore, this paper aims to discuss a comprehensive, system-based
      approach to achieve a factual holistic optimization of patient flows. This paper
      debates the efficacy of Lean principles applied to the optimization of patient
      flows and related activities, structures, and resources, developing a theoretical
      framework based on the principles of the Axiomatic Design. The demand for patient
      oriented and efficient health services leads to use these methodologies to
      improve hospital processes. In the framework, patients with similar
      characteristics are clustered in families to achieve homogeneous flows through
      the value stream. An optimization checklist is outlined as the result of the
      mapping between Functional Requirements and Design Parameters, with the right
      sequence of the steps to optimize the patient flow according to the principles of
      Axiomatic Design. The Axiomatic Design-based top-down implementation of Health
      Care evidence, according to Lean principles, results in a holistic optimization
      of hospital patient flows, by reducing the complexity of the system.

PMID- 29072888
TI  - Mechanical Bed for Investigating Sleep-Inducing Vibration
AB  - In running cars or trains, passengers often feel sleepy. Our study focuses on
      this physiological phenomenon. If a machine can reproduce this phenomenon, it is
      feasible to put a person, such as an insomnia patient or an infant, to sleep
      without any harmful effects. The results of our previous study suggest that low
      frequency vibration induces sleep. This report describes a new mechanical bed for
      inducing sleep and discusses the effects of different vibration conditions. The
      new bed has two active DOFs in the vertical and horizontal directions to examine
      the anisotropy of sensation. The bed includes three main parts: a vertical driver
      unit, a horizontal driver unit, and a unique 2-DOF counterweight system to reduce
      driving force and noise. With regard to motion accuracy, the maximum motion error
      in the vertical direction lifting 75 kg load was only 0.06 mm with a 5.0 mm
      amplitude of a 0.5 Hz sinusoidal wave. The results of excitation experiments with
      10 subjects showed a significant difference in sleep latency between the
      conditions with vibration and without vibration. Furthermore, the average latency
      with insensible vibration (amplitude = 2.4 mm) was shorter than that with
      sensible vibration (amplitude = 7.5 mm). These results suggest the ability of
      appropriate vibration to induce sleep.

PMID- 29072886
TI  - Rapid Field Response to a Cluster of Illnesses and Deaths - Sinoe County,
      Liberia, April-May, 2017.
AB  - On April 25, 2017, the Sinoe County Health Team (CHT) notified the Liberia
      Ministry of Health (MoH) and the National Public Health Institute of Liberia of
      an unknown illness among 14 persons that resulted in eight deaths in Sinoe
      County. On April 26, the National Rapid Response Team and epidemiologists from
      CDC, the World Health Organization (WHO) and the African Field Epidemiology
      Network (AFENET) in Liberia were deployed to support the county-led response.
      Measures were immediately implemented to identify all cases, ascertain the cause
      of illness, and control the outbreak. Illness was associated with attendance at a
      funeral event, and laboratory testing confirmed Neisseria meningitidis in
      biologic specimens from cases. The 2014-2015 Ebola virus disease (Ebola) outbreak
      in West Africa devastated Liberia's already fragile health system, and it took
      many months for the country to mount an effective response to control the
      outbreak. Substantial efforts have been made to strengthen Liberia's health
      system to prevent, detect, and respond to health threats. The rapid and efficient
      field response to this outbreak of N. meningitidis resulted in implementation of
      appropriate steps to prevent a widespread outbreak and reflects improved public
      health and outbreak response capacity in Liberia.

PMID- 29072894
TI  - Medicaid Payment and Delivery System Reform: Early Insights from 10 Medicaid
      Expansion States.
AB  - Issue: Expanded Medicaid enrollment under the Affordable Care Act has heightened
      the importance of states' roles as principal purchasers of health care for low
      income and medically vulnerable populations. Concurrently, the federal government
      has augmented states' purchasing tools. Goal: To examine the evolution of payment
      and delivery system reform in 10 ACA Medicaid expansion states. Methods: Analysis
      of state managed care policies, including a detailed review of purchasing
      documents as well as interviews with senior agency officials in 10 states.
      Findings and Conclusions: States have made health system reform a core element of
      their Medicaid expansions, with the aim of improving access, quality, efficiency,
      and population health. States have sought to incorporate evidence-based practice
      and payment strategies, with an emphasis on populations likely to benefit from
      improved care management and on better integration of treatment for physical and
      behavioral health problems. Seven of 10 are directly engaged in provider payment
      and delivery system reform. Agencies noted the importance of experienced provider
      networks in addressing complex health and social needs, along with managed care's
      role in quality improvement and payment reform. States embrace their roles as
      payers and health care innovators, identifying stability of both coverage and the
      underlying federal policy environment as key factors.

PMID- 29072895
TI  - Low-Frequency Pulsed Electromagnetic Field Is Able to Modulate miRNAs in an
      Experimental Cell Model of Alzheimer's Disease
AB  - The aim of the present study was to investigate on the effects of a low-frequency
      pulsed electromagnetic field (LF-PEMF) in an experimental cell model of
      Alzheimer's disease (AD) to assess new therapies that counteract
      neurodegeneration. In recent scientific literature, it is documented that the
      deep brain stimulation via electromagnetic fields (EMFs) modulates the
      neurophysiological activity of the pathological circuits and produces clinical
      benefits in AD patients. EMFs are applied for tissue regeneration because of
      their ability to stimulate cell proliferation and immune functions via the HSP70
      protein family. However, the effects of EMFs are still controversial and further
      investigations are required. Our results demonstrate the ability of our LF-PEMF
      to modulate gene expression in cell functions that are dysregulated in AD (i.e.,
      BACE1) and that these effects can be modulated with different treatment
      conditions. Of relevance, we will focus on miRNAs regulating the pathways
      involved in brain degenerative disorders.

PMID- 29072896
TI  - Next-Generation Photodynamic Therapy: New Probes for Cancer Imaging and
      Treatment.

PMID- 29072897
TI  - Characterizing Nanoparticles in Biological Matrices: Tipping Points in
      Agglomeration State and Cellular Delivery In Vitro.
AB  - Understanding the delivered cellular dose of nanoparticles is imperative in
      nanomedicine and nanosafety, yet is known to be extremely complex because of
      multiple interactions between nanoparticles, their environment, and the cells.
      Here, we use 3-D reconstruction of agglomerates preserved by cryogenic snapshot
      sampling and imaged by electron microscopy to quantify the "bioavailable dose"
      that is presented at the cell surface and formed by the process of individual
      nanoparticle sequestration into agglomerates in the exposure media. Critically,
      using 20 and 40 nm carboxylated polystyrene-latex and 16 and 85 nm silicon
      dioxide nanoparticles, we show that abrupt, dose-dependent "tipping points" in
      agglomeration state can arise, subsequently affecting cellular delivery and
      increasing toxicity. These changes are triggered by shifts in the ratio of the
      total nanoparticle surface area to biomolecule abundance, with the switch to a
      highly agglomerated state effectively changing the test article midassay,
      challenging the dose-response paradigm for nanosafety experiments. By
      characterizing nanoparticle numbers per agglomerate, we show these tipping points
      can lead to the formation of extreme agglomeration states whereby 90% of an
      administered dose is contained and delivered to the cells by just the top 2% of
      the largest agglomerates. We thus demonstrate precise definition, description,
      and comparison of the nanoparticle dose formed in different experimental
      environments and show that this description is critical to understanding cellular
      delivery and toxicity. We further empirically "stress-test" the commonly used
      dynamic light scattering approach, establishing its limitations to present an
      analysis strategy that significantly improves the usefulness of this popular
      nanoparticle characterization technique.

PMID- 29072901
TI  - Use the Supporting Information, but Do Not Leave Critical Details out of the Main
      Manuscript.

PMID- 29072899
TI  - Bulk Immiscibility at the Edge of the Nanoscale.
AB  - In the quest to identify more effective catalyst nanoparticles for many
      industrially important applications, the Au-Pt system has gathered considerable
      attention. Despite considerable effort the interplay between phase equilibrium
      behavior and surface segregation in Au-Pt nanoparticles is still poorly
      understood. Here we investigate the phase equilibrium behavior of 20 nm Au-Pt
      nanoparticles using a combination of high-resolution scanning transmission
      electron microscopy and a hybrid Monte Carlo and molecular dynamics atomistic
      simulation technique. Our approach takes into account the effects of
      immiscibility, elastic strain, interfacial free energy, and surface segregation.
      This is used to explain two key phenomena taking place in these nanoparticles.
      The first is whether the binary system remains immiscible at the nanoscale, and
      if so what morphology would the secondary phase take. Our findings suggest that
      even at sizes of 20 nm, thermally equilibrated Au-Pt nanoparticles remain largely
      immiscible and behave thermodynamically as bulk-like systems. We explain why 20
      nm Au-Pt nanoparticles phase separate into hemispheres as opposed to a thick
      shelled core-shell structure. These insights are central to further optimization
      of Au-Pt nanoparticles toward enhanced catalytic activities. The phase-separated
      Janus particles observed in this study offer enhanced material functionality
      arising from the nonuniformity of their plasmonic, catalytic, and surface
      properties.

PMID- 29072900
TI  - Design of Porous/Hollow Structured Ceria by Partial Thermal Decomposition of Ce
      MOF and Selective Etching.
AB  - Metal-organic frameworks (MOFs) have been widely used to prepare corresponding
      porous metal oxides via thermal treatment. However, high temperature treatment
      always leads to obtained metal oxides with a large crystallite size, thus
      decreasing their specific surface area. Different from the conventional complete
      thermal decomposition of MOFs, herein, using Ce-MOF as a demonstration, we choose
      partial thermal decomposition of MOF, followed by selective etching to prepare
      porous/hollow structured ceria because of the poor stability of Ce-MOF under
      acidic conditions. Compared with the ceria derived from complete thermal
      decomposition of Ce-MOF, the as-prepared ceria is demonstrated to be a good
      support for copper oxide species during the CO oxidation catalytic reaction.
      Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and hydrogen
      temperature-programmed reduction (H2-TPR) analysis revealed that the as-prepared
      ceria is favorable for strengthening the interaction between the ceria and loaded
      copper oxide species. This work is expected to open a new, simple avenue for the
      synthesis of metal oxides from MOFs via partial thermal decomposition.

PMID- 29072898
TI  - The Epstein-Barr Virus B-ZIP Protein Zta Recognizes Specific DNA Sequences
      Containing 5-Methylcytosine and 5-Hydroxymethylcytosine.
AB  - The Epstein-Barr virus (EBV) B-ZIP transcription factor Zta binds to many DNA
      sequences containing methylated CG dinucleotides. Using protein binding
      microarrays (PBMs), we analyzed the sequence specific DNA binding of Zta to four
      kinds of double-stranded DNA (dsDNA): (1) DNA containing cytosine in both
      strands, (2) DNA with 5-methylcytosine (5mC) in one strand and cytosine in the
      second strand, (3) DNA with 5-hydroxymethylcytosine (5hmC) in one strand and
      cytosine in the second strand, and (4) DNA in which both cytosines in all CG
      dinucleotides contain 5mC. We compared these data to PBM data for three
      additional B-ZIP proteins (CREB1 and CEBPB homodimers and cJun|cFos
      heterodimers). With cytosine, Zta binds the TRE motif TGAC/GTCA as previously
      reported. With CG dinucleotides containing 5mC on both strands, many TRE motif
      variants containing a methylated CG dinucleotide at two positions in the motif,
      such as MGAGTCA and TGAGMGA (where M = 5mC), were preferentially bound. 5mC
      inhibits binding of Zta to both TRE motif half-sites GTCA and CTCA. Like the
      CREB1 homodimer, the Zta homodimer and the cJun|cFos heterodimer more strongly
      bind the C/EBP half-site tetranucleotide GCAA when it contains 5mC. Zta also
      binds dsDNA sequences containing 5hmC in one strand, although the effect is less
      dramatic than that observed for 5mC. Our results identify new DNA sequences that
      are well-bound by the viral B-ZIP protein Zta only when they contain 5mC or 5hmC,
      uncovering the potential for discovery of new viral and host regulatory programs
      controlled by EBV.

PMID- 29072902
TI  - Discovery of a Novel Muscarinic Receptor PET Radioligand with Rapid Kinetics in
      the Monkey Brain.
AB  - Positron emission tomography (PET), together with a suitable radioligand, is one
      of the more prominent methods for measuring changes in synaptic neurotransmitter
      concentrations in vivo. The radioligand of choice for such measurements on the
      cholinergic system is the muscarinic receptor antagonist N-[1-11C]propyl-3
      piperidyl benzilate (PPB). In an effort to overcome the shortcomings with the
      technically cumbersome synthesis of [11C]PPB, we designed and synthesized four
      structurally related analogues of PPB, of which (S,R)-1-methylpiperidin-3-yl)2
      cyclopentyl-2-hydroxy-2-phenylacetate (1) was found to bind muscarinic receptors
      with similar affinity as PPB (3.5 vs 7.9 nM, respectively). (S,R)-1 was
      radiolabeled via N-11C-methylation at high radiochemical purity (>99%) and high
      specific radioactivity (>130 GBq/MUmol). In vitro studies by autoradiography on
      human brain tissue and in vivo studies by PET in nonhuman primates demonstrated
      excellent signal-to-noise ratios and a kinetic profile in brain comparable to
      that of [11C]PBB. (S,R)-[11C]1 is a promising candidate for measuring changes in
      endogenous acetylcholine concentrations.

PMID- 29072903
TI  - Three-Dimensional Printed Thermal Regulation Textiles.
AB  - Space cooling is a predominant part of energy consumption in people's daily life.
      Although cooling the whole building is an effective way to provide personal
      comfort in hot weather, it is energy-consuming and high-cost. Personal cooling
      technology, being able to provide personal thermal comfort by directing local
      heat to the thermally regulated environment, has been regarded as one of the most
      promising technologies for cooling energy and cost savings. Here, we demonstrate
      a personal thermal regulated textile using thermally conductive and highly
      aligned boron nitride (BN)/poly(vinyl alcohol) (PVA) composite (denoted as a
      BN/PVA) fibers to improve the thermal transport properties of textiles for
      personal cooling. The a-BN/PVA composite fibers are fabricated through a fast and
      scalable three-dimensional (3D) printing method. Uniform dispersion and high
      alignment of BN nanosheets (BNNSs) can be achieved during the processing of fiber
      fabrication, leading to a combination of high mechanical strength (355 MPa) and
      favorable heat dispersion. Due to the improved thermal transport property
      imparted by the thermally conductive and highly aligned BNNSs, better cooling
      effect (55% improvement over the commercial cotton fiber) can be realized in the
      a-BN/PVA textile. The wearable a-BN/PVA textiles containing the 3D-printed a
      BN/PVA fibers offer a promising selection for meeting the personal cooling
      requirement, which can significantly reduce the energy consumption and cost for
      cooling the whole building.

PMID- 29072904
TI  - Vertically Illuminated, Resonant Cavity Enhanced, Graphene-Silicon Schottky
      Photodetectors.
AB  - We report vertically illuminated, resonant cavity enhanced, graphene-Si Schottky
      photodetectors (PDs) operating at 1550 nm. These exploit internal photoemission
      at the graphene-Si interface. To obtain spectral selectivity and enhance
      responsivity, the PDs are integrated with an optical cavity, resulting in
      multiple reflections at resonance, and enhanced absorption in graphene. We get a
      wavelength-dependent photoresponse with external (internal) responsivity ~20 mA/W
      (0.25A/W). The spectral selectivity may be further tuned by varying the cavity
      resonant wavelength. Our devices pave the way for developing high responsivity
      hybrid graphene-Si free-space illuminated PDs for optical communications,
      coherence optical tomography, and light-radars.

PMID- 29072905
TI  - Carbon Nanotube as a Tool for Fighting Cancer.
AB  - In 2015, cancer was the cause of almost 22% of deaths worldwide. The high
      frequency of relapsing diseases and metastasis requires the development of new
      diagnostic and therapeutic approaches, and the use of nanomaterials is a
      promising tool for fighting cancer. Among the more extensively studied
      nanomaterials are carbon nanotubes (CNTs), synthesized as graphene sheets, whose
      spiral shape is varied in length and thickness. Their physicochemical features,
      such as the resistance to tension, and thermal and electrical conductivity, allow
      their application in several fields. In this review, we show evidence supporting
      the applicability of CNTs in biomedical practice as nanocarriers for drugs and
      immunomodulatory material, emphasizing their potential for use in cancer
      treatment.

PMID- 29072906
TI  - Effects of Grafting Density on Block Polymer Self-Assembly: From Linear to
      Bottlebrush.
AB  - Grafting density is an important structural parameter that exerts significant
      influences over the physical properties of architecturally complex polymers. In
      this report, the physical consequences of varying the grafting density (z) were
      studied in the context of block polymer self-assembly. Well-defined block
      polymers spanning the linear, comb, and bottlebrush regimes (0 <= z <= 1) were
      prepared via grafting-through ring-opening-metathesis polymerization. omega
      Norbornenyl poly(d,l-lactide) and polystyrene macromonomers were copolymerized
      with discrete comonomers in different feed ratios, enabling precise control over
      both the grafting density and molecular weight. Small-angle X-ray scattering
      experiments demonstrate that these graft block polymers self-assemble into long
      range-ordered lamellar structures. For 17 series of block polymers with variable
      z, the scaling of the lamellar period with the total backbone degree of
      polymerization (d* ~ Nbbalpha) was studied. The scaling exponent alpha
      monotonically decreases with decreasing z and exhibits an apparent transition at
      z ~ 0.2, suggesting significant changes in the chain conformations. Comparison of
      two block polymer systems, one that is strongly segregated for all z (System I)
      and one that experiences weak segregation at low z (System II), indicates that
      the observed trends are primarily caused by the polymer architectures, not
      segregation effects. A model is proposed in which the characteristic ratio
      (Cinfinity), a proxy for the backbone stiffness, scales with Nbb as a function of
      the grafting density: Cinfinity ~ Nbbf(z). The scaling behavior disclosed herein
      provides valuable insights into conformational changes with grafting density,
      thus introducing opportunities for block polymer and material design.

PMID- 29072908
TI  - Theoretical Studies of the Glycosidation of 2-O-Substituted 5-Fluorouracil: N
      Regioselective Synthesis with the Phase-Transfer-Catalysis Method.
AB  - The observed N-regioselective glycosidation of 2-O-substituted 5-fluorouracil (5
      FU) via the phase-transfer-catalysis (PTC) method was investigated
      computationally. The Gibbs free energy reaction barrier of the N-reaction between
      the 5-FU anion and 1-bromo-1-deoxy-2,3,4,6-tetra-O-acetyl-alpha-d-glucopyranose
      was computed at the MP2/6-311++G(2d,p)//B3LYP/6-31+G* level. The calculated
      transition states were, in general, quite "loose", with the ambident reaction
      sites at the N3- or O4-positions on 5-FU located approximately 2.0 A from the
      anomeric carbon. With the SN2 mechanism, the formation of beta-glycosides was
      explained by the characteristics of transition states, and the N-regioselectivity
      was explained by three considerations: (1) the conformations of initial complexes
      and the structural requirement of the reactions; (2) the formation of an ionic
      pair between nBu4N+ and 2-O-substituted 5-FU anions; and (3) the thermodynamic
      conversion of O-glycosides to N-glycosides. The reactions between the
      oxocarbenium ion and the 2-O-substituted 5-FU anions (the fast step of SN1
      mechanism) were also examined at the same level of theory. Because there were no
      "promoters" to extract Br in the PTC method, the SN1 mechanism might have an
      unfavorably high barrier to produce oxocarbenium ion. However, both the formation
      of beta-glycosides and the experimentally observed N-regioselectivity could also
      be explained by the SN1 mechanism: The former was explained by the neighboring
      group participation, and the latter was explained by the formation of ionic pairs
      between nBu4N+ and 2-O-substituted 5-FU anions. The formation of ionic pairs
      possibly changed the diffusion-controlled mechanism into an activation-controlled
      mechanism. Two factors were demonstrated by Marcus theory to play an important
      role for the experimentally observed N-resioselectivity in the PTC method: (1)
      the thermodynamic stability of N-products over O-products; (2) the formation of
      ionic pair between nBu4N+ and 2-O-substituted 5-FU anions.

PMID- 29072909
TI  - Free-Energy Surface Prediction by Flying Gaussian Method: Multisystem
      Representation.
AB  - Flying Gaussian method simulates multiple replicas of the studied system and
      enhances sampling by disfavoring replicas to simultaneously sample similar
      states. The bias potential used for this enhancement is highly dynamic when
      looking at individual replica, which raises concerns about the accuracy of free
      energy surfaces predicted by reweighing methods. Here we show that the bias
      potential can be considered as static when looking at the simulation from a
      multisystem perspective. We present two equations that can be used to predict the
      free-energy surface, and we demonstrate their convergence.

PMID- 29072910
TI  - Density Fluctuation in Aqueous Solutions and Molecular Origin of Salting-Out
      Effect for CO2.
AB  - Using molecular dynamics simulation, we studied the density fluctuations and
      cavity formation probabilities in aqueous solutions and their effect on the
      hydration of CO2. With increasing salt concentration, we report an increased
      probability of observing a larger than the average number of species in the probe
      volume. Our energetic analyses indicate that the van der Waals and electrostatic
      interactions between CO2 and aqueous solutions become more favorable with
      increasing salt concentration, favoring the solubility of CO2 (salting in).
      However, due to the decreasing number of cavities forming when salt concentration
      is increased, the solubility of CO2 decreases. The formation of cavities was
      found to be the primary control on the dissolution of gas, and is responsible for
      the observed CO2 salting-out effect. Our results provide the fundamental
      understanding of the density fluctuation in aqueous solutions and the molecular
      origin of the salting-out effect for real gas.

PMID- 29072907
TI  - Environmental Fate of 14C Radiolabeled 2,4-Dinitroanisole in Soil Microcosms.
AB  - 2,4-Dinitrosanisole (DNAN) is an insensitive munitions component replacing
      conventional explosives. While DNAN is known to biotransform in soils to aromatic
      amines and azo-dimers, it is seldom mineralized by indigenous soil bacteria.
      Incorporation of DNAN biotransformation products into soil as humus-bound
      material could serve as a plausible remediation strategy. The present work
      studied biotransformation of DNAN in soil and sludge microcosms supplemented with
      uniformly ring-labeled 14C-DNAN to quantify the distribution of label in soil,
      aqueous, and gaseous phases. Electron donor amendments, different redox
      conditions (anaerobic, aerobic, sequential anaerobic-aerobic), and the
      extracellular oxidoreductase enzyme horseradish peroxidase (HRP) were evaluated
      to maximize incorporation of DNAN biotransformation products into the
      nonextractable soil humus fraction, humin. Irreversible humin incorporation of
      14C-DNAN occurred at higher rates in anaerobic conditions, with a moderate
      increase when pyruvate was added. Additionally, a single dose of HRP resulted in
      an instantaneous increased incorporation of 14C-DNAN into the humin fraction. 14C
      DNAN incorporation to the humin fraction was strongly correlated (R2 = 0.93) by
      the soil organic carbon (OC) amount present (either intrinsic or amended).
      Globally, our results suggest that DNAN biotransformation products can be
      irreversibly bound to humin in soils as a remediation strategy, which can be
      enhanced by adding soil OC.

PMID- 29072911
TI  - Design of Small-Molecule Active-Site Inhibitors of the S1A Family Proteases as
      Procoagulant and Anticoagulant Drugs.
AB  - Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant
      management in venous thrombosis. While efficacious, they are difficult to use due
      to interpatient dose-response variability and the risks of bleeding. The approval
      of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation
      for the development of direct oral anticoagulants (DOAC), and currently such
      inhibitors of thrombin and fXa are in clinical use. These agents can be used
      without regular coagulation monitoring, but the inherent risk of bleeding
      complications associated with blocking the common coagulation pathway remains.
      Efforts are now underway to develop DOACs that inhibit components of the
      intrinsic and extrinsic coagulation cascades upstream of thrombin and fX.
      Evidence from humans and from transgenic animal models suggests that this
      strategy may provide a better therapeutic margin between antithrombotic and
      antihemostatic effects. Here the design of active-site inhibitors of S1A
      proteases involved in coagulation and fibrinolysis is summarized.

PMID- 29072912
TI  - Straightforward Loading of Imidazole Molecules into Metal-Organic Framework for
      High Proton Conduction.
AB  - A one-step straightforward strategy has been developed to incorporate free
      imidazole molecules into a highly stable metal-organic framework (NENU-3,
      ([Cu12(BTC)8(H2O)12][HPW12O40]).Guest). The resulting material Im@(NENU-3)
      exhibits a very high proton conductivity of 1.82 * 10-2 S cm-1 at 90% RH and 70 
      degrees C, which is significantly higher than 3.16 * 10-4 S cm-1 for Im-Cu@(NENU
      3a) synthesized through a two-step approach with mainly terminal bound imidazole
      molecules inside pores. Single crystal structure reveals that imidazole molecules
      in Im-Cu@(NENU-3a) isolate lattice water molecules and then block proton
      transport pathway, whereas high concentration of free imidazole molecules within
      Im@(NENU-3) significantly facilitate successive proton-hopping pathways through
      formation of hydrogen bonded networks.

PMID- 29072913
TI  - Ultrafast to Ultraslow Dynamics of a Langmuir Monolayer at the Air/Water
      Interface Observed with Reflection Enhanced 2D IR Spectroscopy.
AB  - Monolayers play important roles in naturally occurring phenomena and
      technological processes. Monolayers at the air/water interface have received
      considerable attention, yet it has proven difficult to measure monolayer and
      interfacial molecular dynamics. Here we employ a new technique, reflection
      enhanced two-dimensional infrared (2D IR) spectroscopy, on a carbonyl stretching
      mode of tricarbonylchloro-9-octadecylamino-4,5-diazafluorenerhenium(I) (TReF18)
      monolayers at two surface densities. Comparison to experiments on a water-soluble
      version of the metal carbonyl headgroup shows that water hydrogen bond
      rearrangement dynamics slow from 1.5 ps in bulk water to 3.1 ps for interfacial
      water. Longer time scale fluctuations were also observed and attributed to
      fluctuations of the number of hydrogen bonds formed between water and the three
      carbonyls of TReF18. At the higher surface density, two types of TReF18 minor
      structures are observed in addition to the main structure. The reflection method
      can take usable 2D IR spectra on the monolayer within 8 s, enabling us to track
      the fluctuating minor structures' appearance and disappearance on a tens of
      seconds time scale. 2D IR chemical exchange spectroscopy further shows these
      structures interconvert in 30 ps. Finally, 2D spectral line shape evolution
      reveals that it takes the monolayers hours to reach macroscopic structural
      equilibrium.

PMID- 29072914
TI  - Synthesis of Copper-Chelates Derived from Amino Acids and Evaluation of Their
      Efficacy as Copper Source and Growth Stimulator for Lactuca sativa in Nutrient
      Solution Culture.
AB  - Five tetradentate ligands were synthesized from l-amino acids and utilized for
      the synthesis of Cu(II)-chelates 1-5. The efficacy of Cu(II)-chelates as copper
      (Cu) source and growth stimulator in hydroponic cultivation was evaluated with
      Lactuca sativa. Their stability test was performed at pH 4-10. The results
      suggested that Cu(II)-chelate 3 is the most pH tolerant complex. Levels of Cu,
      Zn, and Fe accumulated in plants supplied with Cu(II)-chelates were compared with
      those supplied with CuSO4 at the same Cu concentration of 8.0 MUM. The results
      showed that Cu(II)-chelate 3 significantly enhanced Cu, Zn, and Fe content in
      shoot by 35, 15, and 48%, respectively. Application of Cu(II)-chelate 3 also
      improved plant dry matter yield by 54%. According to the results, Cu(II)-chelate
      3 demonstrated the highest stimulating effect on plant growth and plant mineral
      accumulation so that it can be used as an alternative to CuSO4 for supplying Cu
      in nutrient solutions and enhancing the plant growth.

PMID- 29072915
TI  - Preserving Spin States upon Reflection: Linear and Nonlinear Responses of a
      Chiral Meta-Mirror.
AB  - Conventional metallic mirrors flip the spin of a circularly polarized wave upon
      normal incidence by inverting the direction of the propagation vector. Altering
      or maintaining the spin state of light waves carrying data is a critical need to
      be met at the brink of photonic information processing. In this work, we report a
      chiral metamaterial mirror that strongly absorbs a circularly polarized wave of
      one spin state and reflects that of the opposite spin in a manner conserving the
      circular polarization. A circular dichroic response in reflection as large as
      ~0.5 is experimentally observed in a near-infrared wavelength band. By imaging a
      fabricated pattern composed of the enantiomeric unit cells, we directly visualize
      the two key features of our engineered meta-mirrors, namely the chiral-selective
      absorption and the polarization preservation upon reflection. Beyond the linear
      regime, the chiral resonances enhance light-matter interaction under circularly
      polarized excitation, greatly boosting the ability of the metamaterial to perform
      chiral-selective signal generation and optical imaging in the nonlinear regime.
      Chiral meta-mirrors, exhibiting giant chiroptical responses and spin-selective
      near-field enhancement, hold great promise for applications in polarization
      sensitive electro-optical information processing and biosensing.

PMID- 29072916
TI  - Comparative Proteomics Analysis Identifies Cdc42-Cdc42BPA Signaling as Prognostic
      Biomarker and Therapeutic Target for Colon Cancer Invasion.
AB  - Metastasis is one of the major causes of treatment failure in the patients with
      colon cancer. The aim of our study is to find key proteins and pathways that
      drive invasion and metastasis in colon cancer. Eight rounds of selection of
      cancer cells invading through matrigel-coated chamber were performed to obtain
      highly invasive colon cancer sublines HCT116-I8 and RKO-I8. Stable Isotope
      Labeling by Amino Acids in Cell Culture technology was used to identify the
      differently expressed proteins, and the proteomics data were analyzed by
      ingenuity pathway analysis. PAK1-PBD immunoprecipitation combined with Western
      blot were carried out to determine Cdc42 activity, and qRT-PCR and Western blot
      were used to determine gene expression. The functional role of Cdc42BPA and Cdc42
      pathway in colon cancer invasion was studied by loss-of-function experiments
      including pharmacological blockade, siRNA knockdown, chamber invasion, and WST-1
      assays. Human colon cancer tissue microarray was analyzed by immunohistochemistry
      for overexpression of Cdc42BPA and its correlation with clinicopathological
      parameters and patient survival outcomes. HCT116-I8 and RKO-I8 cells showed
      significantly stronger invasive potential as well as decreased E-cadherin and
      increased vimentin expressions compared with parental cells. The differently
      expressed proteins in I8 cells compared with parental cells were identified.
      Bioinformatics analysis of proteomics data suggested that Cdc42BPA protein and
      Cdc42 signaling pathway are important for colon cancer invasion, which was
      confirmed by experimental data showing upregulation of Cdc42BPA and higher
      expression of active GTP-bound form of Cdc42 in HCT116-I8 and RKO-I8 cells.
      Functionally, pharmacological and genetic blockade of Cdc42BPA and Cdc42
      signaling markedly suppressed colon cancer cell invasion and reversed epithelial
      mesenchymal transition process. Furthermore, compared with adjacent normal
      tissues, Cdc42BPA expression was significantly higher in colon cancer tissues and
      further upregulated in metastatic tumors in lymph nodes. More importantly,
      Cdc42BPA expression was correlated with metastasis and poor survival of the
      patients with colon cancer. This study provides the first evidence that Cdc42BPA
      and Cdc42 signaling are important for colon cancer invasion, and Cdc42BPA has
      potential implications for colon cancer prognosis and treatment.

PMID- 29072918
TI  - Strategically Designed Antifibrotic Gold Nanoparticles to Prevent Collagen Fibril
      Formation.
AB  - Because uncontrolled accumulation of collagen fibrils has been implicated in a
      series of pathologies, inhibition of collagen fibril formation has become one of
      the necessary strategies to target such collagen-linked complications. The
      presence of hydroxyproline (Hyp) at the Y position in (Gly-X-Y)n sequence pattern
      of collagen is known to facilitate crucial hydrophobic and hydration-linked
      interactions that promote collagen fibril formation. Here, to target such Hyp
      mediated interactions, we have synthesized uniform, thermostable, and
      hemocompatible Hyp coated gold nanoparticles (AuNPsHYP) and have examined their
      inhibition effect on the fibril formation of type I collagen. We found that
      collagen fibril formation is strongly suppressed in the presence of AuNPsHYP and
      no such suppression effect was observed in the presence of free Hyp and control
      Gly-coated nanoparticles at similar concentrations. Both isothermal titration
      calorimetric studies and bioinformatics analysis reveal possible interaction
      between Hyp and (Gly-Pro-Hyp) stretches of collagen triple-helical model
      peptides. Further, gold nanoparticles coated with proline (AuNPsPRO) and
      tryptophan (AuNPsTRP) also suppressed collagen fibril formation, suggesting their
      ability to interfere with aromatic-proline as well as hydrophobic interactions
      between collagen molecules. The Hyp molecules, when surface functionalized, are
      predicted to interfere with the Hyp-mediated forces that drive collagen self
      assembly, and such inhibition effect may help in targeting collagen linked
      pathologies.

PMID- 29072917
TI  - Dual Level Statistical Investigation of Equilibrium Solubility in Simulated
      Fasted and Fed Intestinal Fluid.
AB  - The oral route is the preferred option for drug administration but contains the
      inherent issue of drug absorption from the gastro-intestinal tract (GIT) in order
      to elicit systemic activity. A prerequisite for absorption is drug dissolution,
      which is dependent upon drug solubility in the variable milieu of GIT fluid, with
      poorly soluble drugs presenting a formulation and biopharmaceutical challenge.
      Multiple factors within GIT fluid influence solubility ranging from pH to the
      concentration and ratio of amphiphilic substances, such as phospholipid, bile
      salt, monoglyceride, and cholesterol. To aid in vitro investigation simulated
      intestinal fluids (SIF) covering the fasted and fed state have been developed.
      SIF media is complex and statistical design of experiment (DoE) investigations
      have revealed the range of solubility values possible within each state due to
      physiological variability along with the media factors and factor interactions
      which influence solubility. However, these studies require large numbers of
      experiments (>60) and are not feasible or sensible within a drug development
      setting. In the current study a smaller dual level, reduced experimental number
      (20) DoE providing three arms covering the fasted and fed states along with a
      combined analysis has been investigated. The results indicate that this small
      scale investigation is feasible and provides solubility ranges that encompass
      published data in human and simulated fasted and fed fluids. The measured fasted
      and fed solubility ranges are in agreement with published large scale DoE results
      in around half of the cases, with the differences due to changes in media
      composition between studies. Indicating that drug specific behaviors are being
      determined and that careful media factor and concentration level selection is
      required in order to determine a physiologically relevant solubility range. The
      study also correctly identifies the major single factor or factors which
      influence solubility but it is evident that lower significance factors (for
      example bile salt) are not picked up due to the lower sample number employed. A
      similar issue is present with factor interactions with only a limited number
      available for study and generally not determined to have a significant solubility
      impact due to the lower statistical power of the study. The study indicates that
      a reduced experimental number DoE is feasible, will provide solubility range
      results with identification of major solubility factors however statistical
      limitations restrict the analysis. The approach therefore represents a useful
      initial screening tool that can guide further in depth analysis of a drug's
      behavior in gastrointestinal fluids.

PMID- 29072920
TI  - [Articles of the Hungarian Medical Journal from September, 1991].

PMID- 29072919
TI  - Silver and Palladium Cocatalyzed Carbonylative Activation of Benzotriazoles to
      Benzoxazinones under Neutral Conditions.
AB  - A novel and efficient method for the carbonylative activation of benzotriazoles
      to benzoxazinones has been developed. By using a silver and palladium bimetallic
      catalyst system, a broad range of benzotriazoles were transformed into the
      corresponding benzoxazinones in moderate to good yields with excellent functional
      group tolerance. Notably, this procedure proceeds under neutral conditions.

PMID- 29072921
TI  - [Articles of the Hungarian Medical Journal from April, 1991].

PMID- 29072922
TI  - [Articles of the Hungarian Medical Journal from June, 1991].

PMID- 29072923
TI  - [Articles of the Hungarian Medical Journal from August, 1991].

PMID- 29072924
TI  - [Articles of the Hungarian Medical Journal from May, 1991].

PMID- 29072925
TI  - [Articles of the Hungarian Medical Journal from October, 1991].

PMID- 29072926
TI  - Cell-based Therapy in Sepsis. A Step Closer.

PMID- 29072927
TI  - [Articles of the Hungarian Medical Journal from February, 1991].

PMID- 29072929
TI  - [Articles of the Hungarian Medical Journal from March, 1991].

PMID- 29072928
TI  - Donor Milk Utilization for Healthy Infants: Experience at a Single Academic
      Center.
AB  - BACKGROUND: Banked donor milk (BDM) has historically been used as an alternative
      to formula for preterm infants. Recently, BDM has been endorsed by two national
      organizations for use in healthy infants. We sought to quantify utilization
      trends and characteristics of mothers and their healthy newborns who received BDM
      during their postpartum stay between 2013 and 2016 at a single academic medical
      center. MATERIALS AND METHODS: In this observational study, we used a clinical
      log to identify all infants who received BDM in the well-baby nursery between
      July 2013 and June 2016. From this log, we abstracted data on the numbers of
      babies who received BDM, the quantity of BDM provided, and indications for usage.
      We also collected clinical data from the medical records of a subset of
      corresponding mothers and infants. RESULTS: BDM utilization increased over time
      in healthy infants, with 0.04% of infants before July 2014 receiving BDM compared
      with 4.7% in July 2015 to June 2016. During the same periods, the number of
      bottles provided per infant also increased, from 0.6 bottles per infant to 4.6
      bottles per infant. The most common indications for providing BDM were
      parent/caregiver request (19%) and excessive weight loss/dehydration (17%).
      CONCLUSION: At our center, the use of BDM for healthy infants increased
      substantially over the study period. More research is urgently needed to
      understand the repercussions of this practice on resource utilization as well as
      short- and long-term breastfeeding and health outcomes.

PMID- 29072930
TI  - Correction to: Antioxid Redox Signal 2017; 27(7): 379-397. DOI:
      10.1089/ars.2016.6642.

PMID- 29072931
TI  - Effectiveness and Cost-Effectiveness of Tuina for Chronic Neck Pain: A Randomized
      Controlled Trial Comparing Tuina with a No-Intervention Waiting List.
AB  - OBJECTIVE: To evaluate whether tuina is more effective and cost-effective in
      reducing pain compared to no intervention in patients with chronic neck pain.
      DESIGN: Single-center randomized two-armed controlled trial. SETTING: University
      outpatient clinic specialized in Integrative Medicine. SUBJECTS: Outpatients with
      chronic neck pain were randomly allocated to tuina or no intervention.
      INTERVENTION: Six tuina treatments within 3 weeks. OUTCOME MEASURES: The primary
      outcome was the mean neck pain intensity during the previous 7 days on a visual
      analogue scale after 4 weeks (VAS, 0-100 mm, 0 = no pain, 100 = worst imaginable
      pain). Secondary outcomes included Neck Pain and Disability Scale (NPDS), Neck
      Disability Index (NDI), health-related quality of life (12-item quality-of-life
      questionnaire [SF-12]), medication intake, and cost-effectiveness after 4 and 12
      weeks. Statistical analysis included analysis of covariance adjusted for baseline
      values and a full economic analysis from a societal perspective. RESULTS:
      Altogether, 92 outpatients were included (46 in both groups, 87% female, mean age
      45.4 [standard deviation +/-9.7], and mean VAS 57.7 +/- 11.5). Tuina treatment
      led to a clinically meaningful reduction in neck pain intensity (group
      differences, 4 weeks: -22.8 mm [95% confidence interval, -31.7 to -13.8]; p <
      0.001 and 12 weeks: -17.9 mm [-27.1 to -8.8], p < 0.001). No serious adverse
      events were observed. Total costs as well as quality-adjusted life years (QALYs)
      did not differ significantly between the groups. When taking group differences
      into account independently from their statistical significance, costs per QALY
      gained (incremental cost-effectiveness ratio) would range within a cost-effective
      area from ?7,566 (for costs ?10.28 per session) to ?39,414 (cost ?35 per
      session). CONCLUSION: An additional treatment with six tuina sessions over 3
      weeks was effective, safe and relatively cost-effective for patients with chronic
      neck pain. A future trial should compare tuina to other best care options.

PMID- 29072932
TI  - Global Association of Air Pollution and Cardiorespiratory Diseases: A Systematic
      Review, Meta-Analysis, and Investigation of Modifier Variables.
AB  - BACKGROUND: Little is known about the health risks of air pollution and
      cardiorespiratory diseases, globally, across regions and populations, which may
      differ because of external factors. OBJECTIVES: We systematically reviewed the
      evidence on the association between air pollution and cardiorespiratory diseases
      (hospital admissions and mortality), including variability by energy,
      transportation, socioeconomic status, and air quality. SEARCH METHODS: We
      conducted a literature search (PubMed and Web of Science) for studies published
      between 2006 and May 11, 2016. SELECTION CRITERIA: We included studies if they
      met all of the following criteria: (1) considered at least 1 of these air
      pollutants: carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, or
      particulate matter (PM2.5 or PM10); (2) reported risk for hospital admissions,
      mortality, or both; (3) presented individual results for respiratory diseases,
      cardiovascular diseases, or both; (4) considered the age groups younger than 5
      years, older than 65 years, or all ages; and (5) did not segregate the analysis
      by gender. DATA COLLECTION AND ANALYSIS: We extracted data from each study,
      including location, health outcome, and risk estimates. We performed a meta
      analysis to estimate the overall effect and to account for both within- and
      between-study heterogeneity. Then, we applied a model selection (least absolute
      shrinkage and selection operator) to assess the modifier variables, and, lastly,
      we performed meta-regression analyses to evaluate the modifier variables
      contributing to heterogeneity among studies. MAIN RESULTS: We assessed 2183
      studies, of which we selected 529 for in-depth review, and 70 articles fulfilled
      our study inclusion criteria. The 70 studies selected for meta-analysis encompass
      more than 30 million events across 28 countries. We found positive associations
      between cardiorespiratory diseases and different air pollutants. For example,
      when we considered only the association between PM2.5 and respiratory diseases (
      Figure 1 , we observed a risk equal to 2.7% (95% confidence interval = 0.9%,
      7.7%). Our results showed statistical significance in the test of moderators for
      all pollutants, suggesting that the modifier variables influence the average
      cardiorespiratory disease risk and may explain the varying effects of air
      pollution. CONCLUSIONS: Variables related to aspects of energy, transportation,
      and socioeconomic status may explain the varying effect size of the association
      between air pollution and cardiorespiratory diseases. Public Health Implications.
      Our study provides a transferable model to estimate the health effects of air
      pollutants to support the creation of environmental health public policies for
      national and international intervention.

PMID- 29072934
TI  - Global to Local: Public Health on the Front Lines of Climate Change.

PMID- 29072933
TI  - Outcomes of Climate Change in a Marginalized Population: An Ethnography on the
      Turkana Pastoralists in Kenya.

PMID- 29072935
TI  - The US Health Care Sector's Carbon Footprint: Stomping or Treading Lightly?

PMID- 29072936
TI  - Climate Change, Public Health, and Policy: A California Case Study.
AB  - Anthropogenic activity will bring immediate changes and disruptions to the global
      climate with accompanying health implications. Although policymakers and public
      health advocates are beginning to acknowledge the health implications of climate
      change, current policy approaches are lagging behind. We proposed that 4 key
      policy principles are critical to successful policymaking in this arena:
      mainstreaming, linking mitigation and adaptation policy, applying population
      perspectives, and coordination. We explored California's progress in addressing
      the public health challenges of climate change in the San Joaquin Valley as an
      example. We discussed issues of mental health and climate change, and used the
      San Joaquin Valley of California as an example to explore policy approaches to
      health issues and climate change. The California experience is instructive for
      other jurisdictions.

PMID- 29072937
TI  - The American Public Health Association's 2017 Year of Climate Change and Health:
      Time for Action.

PMID- 29072939
TI  - The Need for Climate and Health Education.

PMID- 29072938
TI  - Green Space and Deaths Attributable to the Urban Heat Island Effect in Ho Chi
      Minh City.
AB  - OBJECTIVES: To quantify heat-related deaths in Ho Chi Minh City, Vietnam, caused
      by the urban heat island (UHI) and explore factors that may alleviate the impact
      of UHIs. METHODS: We estimated district-specific meteorological conditions from
      2010 to 2013 using the dynamic downscaling model and calculated the attributable
      fraction and number of mortalities resulting from the total, extreme, and mild
      heat in each district. The difference in attributable fraction of total heat
      between the central and outer districts was classified as the attributable
      fraction resulting from the UHI. The association among attributable fraction,
      attributable number with a green space, population density, and budget revenue of
      each district was then explored. RESULTS: The temperature-mortality relationship
      between the central and outer areas was almost identical. The attributable
      fraction resulting from the UHI was 0.42%, which was contributed by the
      difference in temperature distribution between the 2 areas. Every 1-square
      kilometer increase in green space per 1000 people can prevent 7.4 deaths caused
      by heat. CONCLUSIONS: Green space can alleviate the impacts of UHIs, although
      future studies conducting a heath economic evaluation of tree planting are
      warranted.

PMID- 29072940
TI  - Bridging Climate, Health, and Equity: A Growing Imperative.

PMID- 29072941
TI  - The Critical Roles of Health Professionals in Climate Change Prevention and
      Preparedness.

PMID- 29072942
TI  - Estimated Global Disease Burden From US Health Care Sector Greenhouse Gas
      Emissions.
AB  - OBJECTIVES: To quantify the increased disease burden caused by US health care
      sector life cycle greenhouse gas (GHG) emissions of 614 million metric tons of
      carbon dioxide equivalents in 2013. METHODS: We screened for health damage
      factors that linked GHG emissions to disease burdens. We selected 5 factors,
      based on appropriate temporal modeling scales, which reflect a range of possible
      GHG emissions scenarios. We applied these factors to health care sector
      emissions. RESULTS: We projected that annual GHG emissions associated with health
      care in the United States would cause 123 000 to 381 000 disability-adjusted life
      years in future health damages, with malnutrition being the largest damage
      category. CONCLUSIONS: Through their contribution to global climate change, GHG
      emissions will negatively affect public health because of an increased prevalence
      of extreme weather, flooding, vector-borne disease, and other effects. As the
      stewards of global health, it is important for health care professionals to
      recognize the magnitude of GHG emissions associated with health care itself, and
      the severity of associated health damages.

PMID- 29072943
TI  - Climate, Birth Weight, and Agricultural Livelihoods in Kenya and Mali.
AB  - OBJECTIVES: To examine an association between climate variability and birth
      weight in Mali and Kenya in relation to the local agricultural specialization.
      METHODS: We combined health and sociodemographic data from the Demographic Health
      Surveys for Kenya (2008 and 2014) and Mali (2006 and 2012) with detailed data on
      precipitation, temperature, and vegetation. We analyzed the association between
      climate variability and birth weight by using multilevel regression models for
      the most common agricultural specializations: food cropping, cash cropping, and
      pastoralism. RESULTS: There are differences in sensitivity to climate among
      different agricultural communities. An additional 100 millimeters of rainfall
      during the 12-month period before birth was associated with a 47-gram (P = .001)
      and 89-gram (P = .10) increase in birth weight for food croppers in Kenya and
      Mali, respectively. Every additional hot month in food-cropping communities in
      Kenya was associated with a 71-gram decrease in birth weight (P = .030), likely
      because of food croppers' limited use of modern agricultural techniques. Overall,
      cash croppers are least sensitive to climate variability in both countries.
      CONCLUSIONS: Effective climate change adaptation strategies are essential for
      protecting and improving health outcomes and should be tailored to local
      households' livelihood strategies.

PMID- 29072944
TI  - Differences in Heat-Related Mortality by Citizenship Status: United States, 2005
      2014.
AB  - OBJECTIVES: To determine whether non-US citizens have a higher mortality risk of
      heat-related deaths than do US citizens. METHODS: We used place of residence
      reported in mortality data from the National Vital Statistics System from 2005 to
      2014 as a proxy for citizenship to examine differences in heat-related deaths
      between non-US and US citizens. Estimates from the US Census Bureau American
      Community Survey of self-reported citizenship status and place of birth provided
      the numbers for the study population. We calculated the standardized mortality
      ratio and relative risk for heat-related deaths between non-US and US citizens
      nationally. RESULTS: Heat-related deaths accounted for 2.23% (n = 999) of deaths
      among non-US citizens and 0.02% (n = 4196) of deaths among US citizens. The age
      adjusted standardized mortality ratio for non-US citizens compared with US
      citizens was 3.4 (95% confidence ratio [CI] = 3.2, 3.6). This risk was higher for
      Hispanic non-US citizens (risk ratio [RR] = 3.6; 95% CI = 3.2, 3.9) and non-US
      citizens aged 18 to 24 years (RR = 20.6; 95% CI = 16.5, 25.7). CONCLUSIONS: We
      found an increased mortality risk among non-US citizens compared with US citizens
      for heat-related deaths, especially those younger and of Hispanic ethnicity.

PMID- 29072945
TI  - Neuroendocrine Tumors of the Breast.
AB  - Primary neuroendocrine tumors of the breast are a rare and underrecognized
      subtype of mammary carcinoma. Neuroendocrine tumors of the breast occur
      predominately in postmenopausal women. The tumors are subclassified into well
      differentiated and poorly differentiated neuroendocrine tumors, and invasive
      breast carcinoma with neuroendocrine features. Well-differentiated tumors show
      architectural similarity to carcinoids of other sites but lack characteristic
      neuroendocrine nuclei. Poorly differentiated neuroendocrine tumors are
      morphologically identical to small cell carcinoma of the lung. Neuroendocrine
      differentiation, seen in up to 30% of invasive breast carcinomas, is most
      commonly associated with mucinous and solid papillary carcinomas. The diagnosis
      of neuroendocrine differentiation requires expression of the neuroendocrine
      markers synaptophysin or chromogranin. The main differential diagnosis is a
      metastatic neuroendocrine tumor from an extramammary site. Neuroendocrine tumors
      of the breast are treated similarly to other invasive breast carcinomas. Although
      no consensus has been reached on the prognosis, most studies suggest a poor
      outcome.

PMID- 29072946
TI  - Histologic Mimics of Basal Cell Carcinoma.
AB  - CONTEXT: - Basal cell carcinoma (BCC) is the most common human malignant neoplasm
      and is a frequently encountered diagnosis in dermatopathology. Although BCC may
      be locally destructive, it rarely metastasizes. Many diagnostic entities display
      morphologic and immunophenotypic overlap with BCC, including nonneoplastic
      processes, such as follicular induction over dermatofibroma; benign follicular
      tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular
      hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell
      carcinoma. Thus, misdiagnosis has significant potential to result in
      overtreatment or undertreatment. OBJECTIVE: - To review key features
      distinguishing BCC from histologic mimics, including current evidence regarding
      immunohistochemical markers useful for that distinction. DATA SOURCES: - Review
      of pertinent literature on BCC immunohistochemistry and differential diagnosis.
      CONCLUSIONS: - In most cases, BCC can be reliably diagnosed by histopathologic
      features. Immunohistochemistry may provide useful ancillary data in certain
      cases. Awareness of potential mimics is critical to avoid misdiagnosis and
      resulting inappropriate management.

PMID- 29072947
TI  - Whole Slide Imaging of Large Format Histology in Prostate Pathology: Potential
      for Information Fusion.

PMID- 29072950
TI  - Biotin Interference in Clinical Immunoassays: A Cause for Concern.

PMID- 29072949
TI  - IgG4-Related Disease: A Reminder for Practicing Pathologists.
AB  - IgG4-related disease (IgG4-RD) is a systemic autoimmune fibroinflammatory disease
      that produces sclerotic, tumefactive masses containing dense lymphoplasmacytic
      infiltrates rich in immunoglobulin (Ig) G4+ plasma cells. Initially characterized
      as a form of autoimmune pancreatitis, the distinctive histopathology of IgG4-RD
      has now been described in almost every organ system. However, because the
      clinical manifestations of IgG4-RD are diverse and nonspecific, the disease may
      go unsuspected until a biopsy or resection specimen is obtained to diagnose a
      presumed malignancy. Pathologists thus play a key role in the diagnosis of IgG4
      RD, and familiarity with its histopathologic features is essential to preventing
      the irreversible comorbidities associated with this treatable disease. This brief
      review outlines the epidemiology, clinical manifestations, and histopathology of
      IgG4-RD, with the aim of furthering pathologists' awareness of and ability to
      diagnose this disorder.

PMID- 29072951
TI  - Myxoinflammatory Fibroblastic Sarcoma: Review and Update.
AB  - Myxoinflammatory fibroblastic sarcoma is a rare soft tissue tumor with most
      occurring in the distal extremities of adult patients. It has a high rate of
      local recurrence and a low rate of metastasis. Because it may appear benign on
      clinical examination, and because the microscopic features are generally
      underrecognized, it is often inadequately treated and misdiagnosed. In this
      review, based upon experience and that of the literature, the intent is to
      highlight salient clinicopathologic features, detail the broad microscopic
      spectrum including high-grade aggressive variants, review the molecular features,
      and discuss its relation to hemosiderotic fibrolipomatous tumor.

PMID- 29072952
TI  - Primary Cutaneous Acral CD8+ T-Cell Lymphoma.
AB  - Primary cutaneous acral CD8+ T-cell lymphoma is a new provisional entity in the
      2016 revision of the World Health Organization classification of lymphoid
      neoplasms. This is a challenging diagnosis because of its rarity, as well as its
      morphologic and immunophenotypic overlap with other CD8+ cytotoxic lymphoid
      proliferations. Appropriate classification of this entity is crucial because of
      its indolent clinical behavior compared with other CD8+ T-cell lymphomas.
      Knowledge of the clinical setting, sites of involvement, and morphologic features
      can aid in correct diagnosis. Here, we review the clinical and pathologic
      features of primary cutaneous acral CD8+ T-cell lymphoma with an emphasis on the
      differential diagnosis among other C8+ T-cell lymphomas.

PMID- 29072953
TI  - Mixed-Phenotype Acute Leukemia: Diagnostic Criteria and Pitfalls.
AB  - Mixed-phenotype acute leukemia (MPAL) is a heterogeneous category in the World
      Health Organization classification that comprises acute leukemias with discrete
      admixed populations of myeloid and lymphoid blasts ("bilineal") or with extensive
      coexpression of lymphoid and myeloid markers in a single blast population
      ("biphenotypic"). Flow cytometric findings suggestive of MPAL are often met with
      consternation by pathologists and oncologists alike, owing to unfamiliarity with
      the disease and uncertainty about how MPAL fits into established paradigms for
      treatment of acute leukemia. The purpose of this review is to explain the
      diagnostic criteria for MPAL, summarize its biological and clinical features, and
      address common diagnostic pitfalls of these unusual leukemias.

PMID- 29072954
TI  - Fetal Vascular Malperfusion.
AB  - CONTEXT: - Fetal vascular malperfusion, also known as fetal thrombotic
      vasculopathy, remains an underrecognized pathologic finding and should be noted
      during placental evaluation. OBJECTIVE: - To review histologic findings, gain
      familiarity with the updated terminology, and to recognize important clinical
      associations with this entity. DATA SOURCES: - University of Michigan cases,
      PubMed search, multiple review articles including recent placental workshop group
      consensus statement, and selected book chapters. CONCLUSIONS: - Multiple
      histologic patterns of fetal vascular malperfusion have been described including
      thrombosis, avascular villi, villous stromal-vascular karyorrhexis, intramural
      fibrin thrombi, and stem villous vascular obliteration. Various underlying
      etiologies can be involved in fetal vascular malperfusion. Cord lesions including
      abnormal insertion, length, and coiling are important causes. Maternal vascular
      malperfusion such as preeclampsia, hypercoagulable states, lupus anticoagulant,
      and sometimes diabetes have been associated with this condition. Fetal cardiac
      dysfunction/malformations and severe fetal inflammatory response in the setting
      of ascending intrauterine infection have also been attributed to this important
      finding. Fetal vascular malperfusion has been implicated in several significant
      and sometimes devastating clinical associations; these include intrauterine
      growth restriction, poor perinatal outcome, fetal demise, and neurodevelopmental
      sequelae. A diagnostic challenge may be encountered in cases with prior
      intrauterine fetal death, since degenerative changes post demise result in a
      similar histomorphologic picture. The diffuse versus the focal nature of the
      lesions may help in the distinction.

PMID- 29072955
TI  - Imaging of Hepatocellular Carcinoma Response After 90Y Radioembolization.
AB  - OBJECTIVE: The purpose of this study is to discuss the imaging modalities and
      response criteria used for assessing hepatocellular carcinoma (HCC) response to
      90Y radioembolization, as well as the imaging appearances of treated tumors.
      CONCLUSION: An understanding of the appearance of HCC after 90Y radioembolization
      is crucial for accurate evaluation of treatment response. Residual tumor necrosis
      and enhancement are essential for assessing response. Multiparametric MRI,
      including DWI and perfusion imaging, plays an emerging role in response
      assessment and outcome prediction.

PMID- 29072956
TI  - Some Pulmonary Emboli Are Normal.

PMID- 29072957
TI  - One Person's View of the Future of Medical Publications, or How I Spent My Summer
      Vacation.

PMID- 29072958
TI  - Medicolegal-Malpractice and Ethical Issues in Radiology.

PMID- 29072960
TI  - Spiritual and Affective Responses to a Physical Church and Corresponding Virtual
      Model.
AB  - Architectural and psychological theories posit that built environments have the
      potential to elicit complex psychological responses. However, few researchers
      have seriously explored this potential. Given the increasing importance and
      fidelity of virtual worlds, such research should explore whether virtual models
      of built environments are also capable of eliciting complex psychological
      responses. The goal of this study was to test these hypotheses, using a church, a
      corresponding virtual model, and an inclusive measure of state spirituality
      ("spiritual feelings"). Participants (n = 33) explored a physical church and
      corresponding virtual model, completing a measure of spiritual feelings after
      exploring the outside and inside of each version of the church. Using spiritual
      feelings after exploring the outside of the church as a baseline measure, change
      in state spirituality was assessed by taking the difference between spiritual
      feelings after exploring the inside and outside of the church (inside-outside)
      for both models. Although this change was greater in response to the physical
      church, there was no significant difference between the two models in eliciting
      such change in spiritual feelings. Despite the limitations of this exploratory
      study, these findings indicate that both built environments and corresponding
      virtual models are capable of evoking complex psychological responses.

PMID- 29072959
TI  - Interleukin-10-Overexpressing Mesenchymal Stromal Cells Induce a Series of
      Regulatory Effects in the Inflammatory System and Promote the Survival of
      Endotoxin-Induced Acute Lung Injury in Mice Model.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life
      threatening inflammatory conditions with no effective pharmacological treatment.
      Previous studies suggested that mesenchymal stromal/stem cell (MSC) infusion
      resulted in better survival in mouse ALI models and presented low toxicity in
      human subjects. Therefore, in this study, we investigated the possibility of
      treating a murine model of ALI using MSCs with constant interleukin-10
      overexpression (IL-10-MSC) by retroviral infection. ALI in mice was induced by
      intratracheal lipopolysaccharides (LPS) instillation. After 96 h, 80% of mice
      receiving IL-10-MSCs survived, whereas the survival rate of the mice receiving
      other treatments was only 20-50%. Mice receiving IL-10-MSCs also demonstrated
      significantly less weight loss (p < 0.01), and lower protein level and TNF
      concentration in the BAL (p < 0.01). Interestingly, IL-10-MSCs given to mice 3
      and 1 day before ALI induction still conferred significant protection against
      ALI. While direct IL-10 transfusion resulted in an intensive, but transient peak
      in serum IL-10 level, IL-10-MSCs provided a milder, but more persistent increase
      in serum IL-10 level, together with significantly higher levels of IL-10
      producing T cells and B cells, both in the spleen and in the lung. IL-10-MSCs
      given 3 days before LPS challenge resulted in higher pulmonary infiltration of IL
      10-producing T cells and B cells in mice. On average, mice that survived the LPS
      challenge for 96 h presented higher pulmonary infiltration of IL-10-producing T
      cells and B cells than mice that deceased within the experimental period.
      Together, these results demonstrated that IL-10-MSCs offered superior protection
      against LPS-induced ALI when given before or at the time of ALI induction, and
      significantly increased the frequencies of IL-10-expressing T cells and B cells.
      IL-10-MSCs may thus represent a promising new treatment option in ALI/ARDS.

PMID- 29072962
TI  - Using partial least squares regression as a predictive tool in describing equine
      third metacarpal bone shape.
AB  - Population variance in bone shape is an important consideration when applying the
      results of subject-specific computational models to a population. In this letter,
      we demonstrate the ability of partial least squares regression to provide an
      improved shape prediction of the equine third metacarpal epiphysis, using two
      easily obtained measurements.

PMID- 29072961
TI  - Reducing Smoking in the US Federal Workforce: 5-Year Health and Economic Impacts
      From Improved Cardiovascular Disease Outcomes.
AB  - OBJECTIVE: We estimated the reduction in number of hospitalizations for acute
      myocardial infarction and stroke as well as the associated health care costs
      resulting from reducing the number of smokers in the US federal workforce during
      a 5-year period. METHODS: We developed a 5-year spreadsheet-based cohort model
      with parameter values from past literature and analysis of national survey data.
      We obtained 2015 data on the federal workforce population from the US Office of
      Personnel Management and data on smoking prevalence among federal workers from
      the 2013-2015 National Health Interview Survey. We adjusted medical costs and
      productivity losses for inflation to 2015 US dollars, and we updated future
      productivity losses for growth. Because of uncertainty about the achievable
      reduction in smoking prevalence and input values (eg, relative risk for acute
      myocardial infarction and stroke, medical costs, and absenteeism), we performed a
      Monte Carlo simulation and sensitivity analysis. RESULTS: We estimated smoking
      prevalence in the federal workforce to be 13%. A 5 percentage-point reduction in
      smoking prevalence could result in 1106 fewer hospitalizations for acute
      myocardial infarction (range, 925-1293), 799 fewer hospitalizations for stroke
      (range, 530-1091), and 493 fewer deaths (range, 494-598) during a 5-year period.
      Similarly, estimated costs averted would be $59 million (range, $49-$63 million)
      for medical costs, $332 million (range, $173-$490 million) for absenteeism, and
      $117 million (range, $93-$142 million) for productivity. CONCLUSION: Reductions
      in the prevalence of smoking in the federal workforce could substantially reduce
      the number of hospitalizations for acute myocardial infarction and stroke, lower
      medical costs, and improve productivity.

PMID- 29072963
TI  - Medicaid Prior Authorization Policies for Medication Treatment of Attention
      Deficit/Hyperactivity Disorder in Young Children, United States, 2015.
AB  - OBJECTIVES: In 2011, the American Academy of Pediatrics updated its guidelines
      for the diagnosis and treatment of children with attention-deficit/hyperactivity
      disorder (ADHD) to recommend that clinicians refer parents of preschoolers (aged
      4-5) for training in behavior therapy and subsequently treat with medication if
      behavior therapy fails to sufficiently improve functioning. Data available from
      just before the release of the guidelines suggest that fewer than half of
      preschoolers with ADHD received behavior therapy and about half received
      medication. About half of those who received medication also received behavior
      therapy. Prior authorization policies for ADHD medication may guide physicians
      toward recommended behavior therapy. Characterizing existing prior authorization
      policies is an important step toward evaluating the impact of these policies on
      treatment patterns. We inventoried existing prior authorization policies and
      characterized policy components to inform future evaluation efforts. METHODS: A
      50-state legal assessment characterized ADHD prior authorization policies in
      state Medicaid programs. We designed a database to capture data on policy
      characteristics and authorization criteria, including data on age restrictions
      and fail-first behavior therapy requirements. RESULTS: In 2015, 27 states had
      Medicaid policies that prevented approval of pediatric ADHD medication payment
      without additional provider involvement. Seven states required that prescribers
      indicate whether nonmedication treatments were considered before Medicaid payment
      for ADHD medication could be approved. CONCLUSION: Medicaid policies on ADHD
      medication treatment are diverse; some policies are tied to the diagnosis and
      treatment guidelines of the American Academy of Pediatrics. Evaluations are
      needed to determine if certain policy interventions guide families toward the use
      of behavior therapy as the first-line ADHD treatment for young children.

PMID- 29072964
TI  - Thoracoscopic Rib Resection in Children.
AB  - OBJECTIVE: The authors present a multicenter retrospective series of different
      benign rib lesions in children operated on using thoracoscopy. MATERIALS AND
      METHODS: Between 2005 and 2015, 17 rib resections were performed
      thoracoscopically, in four French departments of pediatric surgery. Of these 17
      cases, 13 exostoses, 2 endochondromas, 1 synostosis, and 1 Cyriax's syndrome were
      noted. Inclusion criteria were benign tumors or rib anomalies such as synostosis,
      in children younger than the age of 18 years, and thoracoscopy. Open surgery and
      malignant tumors were excluded. Thoracoscopy was put forward using one optical
      port as well as one or two operative ports. RESULTS: Ten patients presented with
      chest pain, dyspnea, or unexplained cough. Six tumors were incidentally
      diagnosed. One patient presented with a chest wall deformation. Single-lung
      ventilation was required in 2 cases. In 1 case of endochondroma, a segmental rib
      resection was performed, leaving a part of the periosteum and the intercostal
      vessels and nerve. In this case, rib resection was performed using an endoscopic
      shaver drill system. As for the other cases, a simple resection of the tumor or
      of the bridge between two ribs (synostosis) was performed. In these cases, a
      Codman Kerrison laminectomy rongeur was used. There was no complication during or
      after surgery. Nevertheless, 2 years after surgery, pain did not disappear in 1
      case, probably due to a definitive intercostal nerve damage. CONCLUSION: Benign
      rib lesions in children are rare. Thoracoscopy may be offered to reduce the
      functional deleterious consequences of an open surgery. It may be put forward
      especially in case of hereditary multiple exostoses where redo procedures may be
      required.

PMID- 29072965
TI  - In Vitro Tissue Microarrays for Quick and Efficient Spheroid Characterization.
AB  - Three-dimensional (3D) in vitro microphysiological cultures, such as spheroids
      and organoids, promise increased patient relevance and therapeutic predictivity
      compared with reductionist cell monolayers. However, high-throughput
      characterization techniques for 3D models are currently limited to simplistic
      live/dead assays. By sectioning and staining in vitro microtissues, researchers
      can examine their structure; detect DNA, RNA, and protein targets; and visualize
      them at the level of single cells. The morphological examination and
      immunochemistry staining for in vitro cultures has historically been done in a
      laborious manner involving testing one set of cultures at a time. We have
      developed a technology to rapidly screen spheroid phenotype and protein
      expression by arranging 66 spheroids in a gel array for paraffin embedding,
      sectioning, and immunohistochemsitry. The process is quick, mostly automatable,
      and uses 11 times less reagents than conventional techniques. Here we showcase
      the capabilities of the technique in an array made up of 11 different cell lines
      stained in conventional hematoxylin and eosin (H&E) staining, as well as
      immunohistochemistry staining for estrogen (ER), progesterone (PR), and human
      epidermal growth factor (Her-2) receptors, and TP53. This new methodology can be
      used in optimizing stem cell-based models of disease and development, for tissue
      engineering, safety screening, and efficacy screens in cancer research.

PMID- 29072966
TI  - Multi-body optimization with subject-specific knee models: performance at high
      knee flexion angles.
AB  - When estimating knee kinematics from skin markers and stereophotogrammetry, multi
      body optimization (MBO) has provided promising results for reducing soft tissue
      artefacts (STA), but can still be improved. The goal of this study was to assess
      the performance of MBO with subject-specific knee models at high knee flexion
      angles (up to 110 degrees ) against knee joint kinematics measured by magnetic
      resonance imaging. Eight subjects were recruited. MBO with subject-specific knee
      models was more effective in compensating STA compared to no kinematic and
      spherical constraints, in particular for joint displacements. Moreover, it seems
      to be more reliable over large ranges of knee flexion angle. The ranges of root
      mean square errors for knee rotations/displacements were 3.0 degrees -9.2 degrees
      /1.3-3.5 mm for subject-specific knee models, 6.8 degrees -8.7 degrees /6.0-12.4
      mm without kinematic constraint and 7.1 degrees -9.8 degrees /4.9-12.5 mm for
      spherical constraints.

PMID- 29072967
TI  - Association of VDR gene polymorphisms with risk of relapsing-remitting multiple
      sclerosis in an Iranian Kurdish population.
AB  - PURPOSE: The purpose of this study was to evaluate the association of VDR Apa-I,
      Bsm-I, Fok-I, Taq-I single nucleotide polymorphisms (SNPs) with multiple
      sclerosis (MS) risk in an Iranian Kurdish population. MATERIALS AND METHODS: A
      population including of 118 patients and 124 healthy matched controls were
      recruited to the study. Genotyping of the SNPs was accomplished using polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The
      frequency of allele T of Fok-I (P = 0.003) and allele C of Taq-I (P = 0.0003) was
      significantly different between case and control subjects and showed significant
      association with risk of MS (OR = 1.84, 95% CI = 1.23-2.76; OR = 1.98, 95% CI =
      1.36-2.87, respectively). CT genotype (OR = 1.7, 95% CI = 1.05-2.99) of Fok-I and
      CC genotype (OR = 2.18, 95% CI = 1.05-4.52) of Taq-I showed a predisposing
      effect. Combined TT+TC vs. CC for Fok-I (OR = 2.15, 95% = CI 1.29-3.60) and
      combined CC+TC vs. TT for Taq-I (OR = 2.58, 95% CI 1.51-4.40) were susceptibility
      genotypes for MS. Apa-I and Bsm-I were not significantly associated with risk of
      MS (OR < 1, P > 0.05) and any genotypes in any genetic models were not
      significantly different between cases and controls (P > 0.05). CONCLUSION: As a
      result, Fok-I and Taq-I showed significant association with risk of MS, while Apa
      I and Bsm-I were not observed to be related to the risk of the disease in this
      population.

PMID- 29072968
TI  - Providing Standards for Diabetes Care in the School Setting: A Review of the
      Colorado Model.
AB  - In 2013, a collaboration of organizations in Colorado developed a set of
      standards to address school nurses' need for current diabetes care practices in
      the school setting. The Standards of Care for Diabetes Management in the School
      Setting are successful in meeting the needs of the school nurses in Colorado and
      are updated annually to continue to provide valid guidelines as diabetes care
      continues to become more technological and new approaches are adopted. A review
      of the standards, including background, development, contents, evaluations, and
      ongoing additions, is provided in this article.

PMID- 29072969
TI  - A new benzofuran derivative from the leaves of Ficus pumila L.
AB  - A new benzofuran derivative, pumiloside (1), together with seven known flavonoid
      glycosides, afzelin (2), astragalin (3), quercitrin (4), isoquercitrin (5),
      kaempferol 3-O-rutinoside (6), rutin (7) and kaempferol 3-O-sophoroside (8) were
      isolated from the leaves of Ficus pumila. Their structures were established by
      spectroscopic data and comparison with the literature values.

PMID- 29072971
TI  - Validation of the patient-completed asthma knowledge questionnaire (PAKQ).
AB  - BACKGROUND: Asthma is often suboptimally controlled, in part due to patients'
      disease knowledge. Understanding patients' knowledge, prior to education may help
      in individualizing content. However, there are no well validated or
      internationally relevant patient asthma knowledge questionnaires available.
      OBJECTIVE: To translate and validate the rigorously validated Questionnaire de
      connaissances sur l'asthme destine aux patients adultes (QCA-PA) based on key
      points related to asthma knowledge and self-management accordingly to the Global
      Initiative for Asthma report. METHODS: Based on Vallerand's methodology, a
      preliminary version of the "Patient-completed Asthma Knowledge Questionnaire"
      (PAKQ) was back-translated and evaluated by an expert committee. A sample of 20
      individuals with asthma pretested the questionnaire, after which 62 adults were
      recruited. Sociodemographic data were collected and the PAKQ together with a
      comparator questionnaire (Consumer Questionnaire (CQ)) were completed. Fourteen
      days after the first visit, participants returned to recomplete both
      questionnaires; half were randomly selected to receive a one-on-one asthma
      education session and again completed both questionnaires immediately after
      education, and at 10 days follow-up. RESULTS: The PAKQ showed good internal
      consistency (KR-20 = 0.77). Moderate correlation with CQ (r = 0.596, p = 0.01)
      attested to its concurrent validity. Confirmatory factor analyses confirmed a
      single factor structure. A repeated measures ANOVA showed its reproducibility (n
      = 21:F(1) = 3.578, p = 0.07, etap2 = 0.152) and responsiveness (n = 21:F(1) =
      26.041, P < 0.05, etap2 = 0.566). CONCLUSION: The PAKQ is a valid asthma
      knowledge questionnaire which is based on international asthma recommendations
      and could help healthcare professionals in individualizing educational
      interventions for people with asthma.

PMID- 29072970
TI  - Dipteryx alata Vogel May Improve Lipid Profile and Atherogenic Indices in Wistar
      Rats Dipteryx alata and Atherogenic Indices.
AB  - Worldwide prevalence of noncommunicable chronic degenerative diseases is among
      the main causes of death worldwide. The consumption of some foods such as nuts
      and seeds may be beneficial in preventing these diseases. Dipteryx alata Vogel
      (DA), known popularly as Baru, belongs to the family Fabaceae and is a native
      fruit tree from the Brazilian savanna. The purpose of this study was to evaluate
      the use of seeds of DA on the metabolic and oxidative profile of Wistar rats.
      Animals were divided randomly into four groups (n = 10): G1 (control group), and
      G2 (treated with DA 20%), G3 (treated with DA 30%), and G4 (treated with DA 40%).
      After 40 days, animals were euthanized and metabolic and oxidative profiles were
      analyzed (glycemia, cholesterol, triglycerides [TGs], high-density lipoprotein
      cholesterol [HDL-c], very low-density lipoprotein-cholesterol [VLDL-c], low
      density lipoprotein-cholesterol [LDL-c], C reactive protein, aspartate
      aminotransferase, alanine aminotransferase, Lee index, weight, visceral fat,
      ferric reducing ability of plasma, and ferric-xylenol orange method. The use of
      the seeds was effective in reducing TGs, VLDL-c, LDL-c, and increasing HDL-c but
      did not interfere in the percentage of weight gain, visceral fat, levels of total
      cholesterol, and oxidative stress. Based on our results, it is possible to say
      that the use of DA may improve the lipid profile of Wistar rats and we may
      suggest that the consumption of DA almonds or products prepared with them may be
      an effective option for the intake of healthy products.

PMID- 29072972
TI  - Incision Classification Accuracy: Do Residents Know How to Classify Them?
AB  - BACKGROUND: It is unclear whether surgical residents understand how to classify
      incisions, which may impact how closure is handled in the operating room. We
      hypothesized that surgical residents define incision class (IC) accurately
      compared with an attending NSQIP surgeon champion (SC). METHODS: We evaluated our
      NSQIP database from April 1, 2015, to December 31, 2016, including cases in which
      a resident was present and IC was documented. Cases in which the resident,
      circulator, or surgical clinical rater disagreed on the IC were then reviewed by
      a blinded SC. RESULTS: Residents were correct in 83.6% of the cases, with PGY 5
      persons having the lowest accuracy. Class 3 incisions were most often
      misclassified (36%). A disproportionate number of misclassifications by PGY4 and
      PGY5-7 residents occurred in incision classes 2 and 3. Surgical site infections
      occurred in 7.4% of cases, ranging from 2.4% in IC 1 to 15.7% in IC 4 cases.
      CONCLUSIONS: Although overall accuracy appears reasonable, it is of concern that
      incisions at higher risk of infection (contaminated) were least likely to be
      classified appropriately. Chief residents, who often are making the decisions on
      incision closure, were the least accurate in determining IC. This may have a
      deleterious impact on incision management, suggesting a need for directed
      resident education on IC and further investigation to determine its impact on
      site infection risk and patient outcomes.

PMID- 29072973
TI  - Need for Comprehensive Counseling in Women Requesting Oocyte Cryopreservation.
AB  - OBJECTIVES: The aim of this study is to assess current counseling recommendations
      for women undergoing elective oocyte cryopreservation. DATA SOURCES: PubMed and
      Clinical Key. MATERIALS AND METHODS: A search of PubMed and Clinical Key was
      conducted to assess current counseling practices for elective oocyte
      cryopreservation. RESULTS: It is substantiated that uniform counseling guidelines
      are lacking for this group of assisted reproductive technology (ART) patients
      presenting only for cryopreserving their oocytes. However, although a woman may
      be a suitable candidate for pregnancy at the point that she undergoes oocyte
      cryopreservation, possibly many years later, at the time of oocyte thawing, this
      same woman may have multiple risk factors, which will increase her risk for
      pregnancy-related maternal and fetal morbidity and mortality. CONCLUSIONS: Given
      the increasing use of oocyte cryopreservation, data support that women be
      extensively counseled at the time they are requesting elective oocyte
      cryopreservation for future use in the same manner that they are counseled when
      requesting ART for pursuing an immediate pregnancy.

PMID- 29072974
TI  - The Occurrence of Antibodies Against Gluten in Children with Autism Spectrum
      Disorders Does Not Correlate with Serological Markers of Impaired Intestinal
      Permeability.
AB  - There is evidence that children with autism spectrum disorders (ASDs) display an
      increased immune reactivity against gluten, which is supposed to be the effect of
      intestinal barrier abnormalities. The aim of study was to evaluate the relation
      of antibody induced by gluten to zonulin and intestinal fatty acid binding
      proteins (I-FABP), that is, serological markers of an impaired gut barrier. The
      study included 77 patients with ASDs. Zonulin, I-FABP, celiac-specific
      antibodies, anti-gliadin antibodies (AGA), and antibodies against neural
      transglutaminase 6 (TG6) of immunoglobulin (Ig) A and IgG classes were detected
      in sera. Celiac-specific antibodies were negative in all ASD children, four
      children (5.2%) had positive anti-TG6 antibodies, and increased AGA-IgG
      production was found in 21 patients (27.3%). Mean levels of zonulin and I-FABP in
      ASD patients were similar to those found in healthy controls and revealed a
      negative correlation with age, whereas regression analysis revealed a significant
      positive relationship between antibody production and the age. Serum
      concentrations of zonulin and I-FABP showed no statistically significant
      association with antibody positivity. An increased production of antibodies
      related to gliadin and neural TG6 in ASD children is not related to serological
      markers of an impaired intestinal barrier.

PMID- 29072975
TI  - Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or
      Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.
AB  - Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and
      trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic
      thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor
      patient outcomes and no systemic therapies with clinical benefit. Methods In this
      phase II, open-label trial, patients with predefined BRAF V600E-mutated
      malignancies received dabrafenib 150 mg twice daily and trametinib 2 mg once
      daily until unacceptable toxicity, disease progression, or death. The primary end
      point was investigator-assessed overall response rate. Secondary end points
      included duration of response, progression-free survival, overall survival, and
      safety. Results Sixteen patients with BRAF V600E-mutated anaplastic thyroid
      cancer were evaluable (median follow-up, 47 weeks; range, 4 to 120 weeks). All
      patients had received prior radiation treatment and/or surgery, and six had
      received prior systemic therapy. The confirmed overall response rate was 69% (11
      of 16; 95% CI, 41% to 89%), with seven ongoing responses. Median duration of
      response, progression-free survival, and overall survival were not reached as a
      result of a lack of events, with 12-month estimates of 90%, 79%, and 80%,
      respectively. The safety population was composed of 100 patients who were
      enrolled with seven rare tumor histologies. Common adverse events were fatigue
      (38%), pyrexia (37%), and nausea (35%). No new safety signals were detected.
      Conclusion Dabrafenib plus trametinib is the first regimen demonstrated to have
      robust clinical activity in BRAF V600E-mutated anaplastic thyroid cancer and was
      well tolerated. These findings represent a meaningful therapeutic advance for
      this orphan disease.

PMID- 29072976
TI  - International Assessment of Event-Free Survival at 24 Months and Subsequent
      Survival in Peripheral T-Cell Lymphoma.
AB  - Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We
      have previously shown that event-free survival (EFS) at 24 months (EFS24) is a
      clinically useful end point in diffuse large B-cell lymphoma. Here, we assess
      EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts.
      Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to
      2012 and treated with curative intent were included from the United States and
      Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as
      time from date of diagnosis to progression after primary treatment, retreatment,
      or death. Subsequent OS was measured after achieving EFS24 or from the time of
      progression if it occurred within 24 months. OS rates were compared with the age
      , sex-, and country-matched general population. Results Seven hundred seventy
      five patients were included in the study (the median age at diagnosis was 64
      years; 63% were men). Results were similar in the initial and replication
      cohorts, and a combined analysis was undertaken. Sixty-four percent of patients
      progressed within the first 24 months and had a median OS of only 4.9 months (5
      year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5
      year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in
      23% of patients. Superior outcomes after achieving EFS24 were observed in younger
      patients (<= 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies
      subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or
      early relapse have extremely poor survival. However, more than one third of
      patients with PTCL remain in remission 2 years after diagnosis with encouraging
      subsequent OS, especially in younger patients. These marked differences in
      outcome suggest that EFS24 has utility for patient counseling, study design, and
      risk stratification in PTCL.

PMID- 29072978
TI  - Maintenance Poly (ADP-ribose) Polymerase Inhibitor Therapy for Ovarian Cancer:
      Precision Oncology or One Size Fits All?

PMID- 29072977
TI  - Long-Term Follow-Up of Cardiac Function and Quality of Life for Patients in NSABP
      Protocol B-31/NRG Oncology: A Randomized Trial Comparing the Safety and Efficacy
      of Doxorubicin and Cyclophosphamide (AC) Followed by Paclitaxel With AC Followed
      by Paclitaxel and Trastuzumab in Patients With Node-Positive Breast Cancer With
      Tumors Overexpressing Human Epidermal Growth Factor Receptor 2.
AB  - Purpose Early cardiac toxicity is a risk associated with adjuvant chemotherapy
      plus trastuzumab. However, objective measures of cardiac function and health
      related quality of life are lacking in long-term follow-up of patients who remain
      cancer free after completion of adjuvant treatment. Patients and Methods Patients
      in NSABP Protocol B-31 received anthracycline and taxane chemotherapy with or
      without trastuzumab for adjuvant treatment of node-positive, human epidermal
      growth factor receptor 2-positive early-stage breast cancer. A long-term follow
      up assessment was undertaken for patients who were alive and disease free, which
      included measurement of left ventricular ejection fraction by multigated
      acquisition scan along with patient-reported outcomes using the Duke Activity
      Status Index (DASI), the Medical Outcomes Study questionnaire, and a review of
      current medications and comorbid conditions. Results At a median follow-up of 8.8
      years among eligible participants, five (4.5%) of 110 in the control group and 10
      (3.4%) of 297 in the trastuzumab group had a > 10% decline in left ventricular
      ejection fraction from baseline to a value < 50%. Lower DASI scores correlated
      with age and use of medications for hypertension, cardiac conditions, diabetes,
      and hyperlipidemia, but not with whether patients had received trastuzumab.
      Conclusion In patients without underlying cardiac disease at baseline, the
      addition of trastuzumab to adjuvant anthracycline and taxane-based chemotherapy
      does not result in long-term worsening of cardiac function, cardiac symptoms, or
      health-related quality of life. The DASI questionnaire may provide a simple and
      useful tool for monitoring patient-reported changes that reflect cardiac
      function.

PMID- 29072979
TI  - Cervical Internal Carotid Occlusion versus Pseudo-occlusion at CT Angiography in
      the Context of Acute Stroke: An Accuracy, Interobserver, and Intraobserver
      Agreement Study.
AB  - Purpose To evaluate the diagnostic accuracy and reliability of computed
      tomographic (CT) angiography to distinguish true cervical internal carotid artery
      (ICA) occlusion from pseudo-occlusion (defined as an isolated intracranial
      thrombus that impedes ascending blood flow) in the context of acute stroke.
      Materials and Methods This was a retrospective study of patients who underwent
      thrombectomy with preprocedural CT angiography that helps to demonstrate a lack
      of attenuation in the cervical ICA on the symptomatic side (24 men and 13 women;
      mean age, 63 years; age range, 30-86 years). Seven readers, including five
      neuroradiologists and two interventional neuroradiology fellows, independently
      reviewed the CT angiography images to assess whether there was true cervical ICA
      occlusion. Their results were compared with digital subtraction angiography (DSA)
      as the reference standard. Sensitivity and specificity for detecting true
      occlusion as well as accuracy and diagnostic odds ratio were calculated, with
      inter- and intraobserver kappa statistics. Results Cervical ICA pseudo-occlusion
      occurred in 12 of 37 patients (32.4%) with nonattenuation of the cervical ICA on
      the symptomatic side. Interobserver agreement coefficients did not reach the
      substantial value of 0.61 for either pairs or groups of readers. The cohort's
      average sensitivity and specificity was 68% (95% confidence interval [CI]: 59%,
      76%) and 75% (95% CI: 71%, 80%), respectively, with a diagnostic odds ratio of 8
      (95% CI: 3, 18) and only fair interobserver agreement (kappa = 0.32; 95% CI:
      0.16, 0.47). Conclusion In the context of acute ischemic stroke with ipsilateral
      ICA nonattenuation at single-phase CT angiography, even specialized radiologists
      may not reliably distinguish true cervical occlusion from pseudo-occlusion. (c)
      RSNA, 2017 Online supplemental material is available for this article.

PMID- 29072980
TI  - Focal Liver Lesions: Computer-aided Diagnosis by Using Contrast-enhanced US Cine
      Recordings.
AB  - Purpose To assess the performance of computer-aided diagnosis (CAD) systems and
      to determine the dominant ultrasonographic (US) features when classifying benign
      versus malignant focal liver lesions (FLLs) by using contrast material-enhanced
      US cine clips. Materials and Methods One hundred six US data sets in all subjects
      enrolled by three centers from a multicenter trial that included 54 malignant, 51
      benign, and one indeterminate FLL were retrospectively analyzed. The 105 benign
      or malignant lesions were confirmed at histologic examination, contrast-enhanced
      computed tomography (CT), dynamic contrast-enhanced magnetic resonance (MR)
      imaging, and/or 6 or more months of clinical follow-up. Data sets included 3
      minute cine clips that were automatically corrected for in-plane motion and
      automatically filtered out frames acquired off plane. B-mode and contrast
      specific features were automatically extracted on a pixel-by-pixel basis and
      analyzed by using an artificial neural network (ANN) and a support vector machine
      (SVM). Areas under the receiver operating characteristic curve (AUCs) for CAD
      were compared with those for one experienced and one inexperienced blinded
      reader. A third observer graded cine quality to assess its effects on CAD
      performance. Results CAD, the inexperienced observer, and the experienced
      observer were able to analyze 95, 100, and 102 cine clips, respectively. The AUCs
      for the SVM, ANN, and experienced and inexperienced observers were 0.883 (95%
      confidence interval [CI]: 0.793, 0.940), 0.829 (95% CI: 0.724, 0.901), 0.843 (95%
      CI: 0.756, 0.903), and 0.702 (95% CI: 0.586, 0.782), respectively; only the
      difference between SVM and the inexperienced observer was statistically
      significant. Accuracy improved from 71.3% (67 of 94; 95% CI: 60.6%, 79.8%) to
      87.7% (57 of 65; 95% CI: 78.5%, 93.8%) and from 80.9% (76 of 94; 95% CI: 72.3%,
      88.3%) to 90.3% (65 of 72; 95% CI: 80.6%, 95.8%) when CAD was in agreement with
      the inexperienced reader and when it was in agreement with the experienced
      reader, respectively. B-mode heterogeneity and contrast material washout were the
      most discriminating features selected by CAD for all iterations. CAD selected
      time-based time-intensity curve (TIC) features 99.0% (207 of 209) of the time to
      classify FLLs, versus 1.0% (two of 209) of the time for intensity-based features.
      None of the 15 video-quality criteria had a statistically significant effect on
      CAD accuracy-all P values were greater than the Holm-Sidak alpha-level correction
      for multiple comparisons. Conclusion CAD systems classified benign and malignant
      FLLs with an accuracy similar to that of an expert reader. CAD improved the
      accuracy of both readers. Time-based features of TIC were more discriminating
      than intensity-based features. (c) RSNA, 2017 Online supplemental material is
      available for this article.

PMID- 29072981
TI  - Effect of Background Parenchymal Enhancement on Breast MR Imaging Interpretive
      Performance in Community-based Practices.
AB  - Purpose To evaluate the effect of background parenchymal enhancement (BPE) on
      breast magnetic resonance (MR) imaging interpretive performance in a large multi
      institutional cohort with independent analysis of screening and diagnostic MR
      studies. Materials and Methods Analysis of 3770 breast MR studies was conducted.
      Examinations were performed in 2958 women at six participating facilities in the
      San Francisco Bay Area from January 2010 to October 2012. Findings were recorded
      prospectively in the San Francisco Mammography Registry. Performance measures
      were compared between studies with low BPE (mild or minimal) and those with high
      BPE (moderate or marked) by using binomial tests of proportions. Results Of 1726
      MR imaging studies in the screening group, 1301 were classified as having low BPE
      and 425 were classified as having high BPE (75% vs 25%, respectively; P < .001).
      Of 2044 MR imaging studies in the diagnostic group, 1443 were classified as
      having low BPE and 601 were classified as having high BPE (71% vs 29%,
      respectively; P < .001). For low versus high BPE groups at screening, abnormal
      interpretation rate was 157 of 1301 versus 111 of 424 (12% vs 26%, P < .001);
      biopsy recommendation rate was 85 of 1301 versus 54 of 424 (7% vs 13%, P < .001);
      and specificity was 89% (95% confidence interval [CI]: 87, 91) versus 75% (95%
      CI: 71, 80) (P = .01). For the low versus high BPE groups at diagnostic MR
      imaging, biopsy recommendation rate was 325 of 1443 versus 195 of 601 (23% vs
      32%, P < .001); and specificity was 86% (95% CI: 84, 88) versus 75% (95% CI: 74,
      82) (P < .001). There were no significant differences between studies with low
      versus high BPE in sensitivity for screening (76% [95% CI: 55, 91] vs 83% [95%
      CI: 52, 98]; P = .94) or diagnostic (93% [95% CI: 87, 97] vs 96% [95% CI: 87,
      99]; P = .69) MR imaging, nor were there significant differences in cancer
      detection rate per 1000 patients between the low BPE versus high BPE groups for
      screening (15 per 1000 vs 24 per 1000, P = .30) or diagnostic (78 per 1000 vs 85
      per 1000, P = .64) MR imaging. Conclusion Relative to MR studies with minimal or
      mild BPE, those with moderate or marked BPE were associated with higher abnormal
      interpretation and biopsy rates and lower specificity, with no difference in
      cancer detection rate. (c) RSNA, 2017 Online supplemental material is available
      for this article.

PMID- 29072982
TI  - Adipose Triglyceride Lipase Gene Polymorphisms is Not Associated with Free Fatty
      Acid Levels in Chinese Han Population.
AB  - BACKGROUND: Elevated levels of free fatty acids (FFAs) play a role in the
      pathogenesis of insulin resistance and atherosclerosis. Adipose triglyceride
      lipase (also defined as patatin-like phospholipase domain containing 2 or PNPLA2)
      has been demonstrated to contribute to the release of FFA. The aim of this study
      was to investigate the association of PNPLA2 gene variations with FFA levels in
      healthy Chinese Han population. METHODS: Single-nucleotide polymorphisms of
      PNPLA2 were genotyped using TaqMan method to perform association studies with
      serum level of FFA and other lipid parameters in 1765 subjects among healthy
      Chinese Han population. All the subjects were divided into two groups: normal
      FFAs group (FFAs <=0.88 mmol/L) and high FFAs group (FFAs >0.88 mmol/L). RESULTS:
      Neither rs7925131 nor rs7942159 was significantly associated with FFA level. We
      observed no difference in the genotype frequency of rs7925131 or rs7942159
      between the normal FFA group and the high FFA group. CONCLUSIONS: Our results do
      not support an association of rs7925131 or rs7942159 with the FFA levels among
      the Chinese Han population.

PMID- 29072984
TI  - Disparities in Preventive Dental Care Among Children in Georgia.
AB  - INTRODUCTION: We compared access to preventive dental care among low-income
      children eligible for public dental insurance to access among children with
      private dental insurance and/or high family income (>400% of the federal poverty
      level) in Georgia, and the effect of policies toward increasing access to dental
      care for low-income children. METHODS: We used multiple sources of data (eg, US
      Census, Georgia Board of Dentistry) to estimate, by census tract, measures of
      preventive dental care access in 2015 for children aged 0 to 18 years. Measures
      were percentage of met need, 1-way travel distance to a dentist, and scarcity of
      dentists. We used an optimization model to estimate access, quantify disparities,
      and evaluate policies. RESULTS: About 1.5 million children were eligible for
      public insurance; 600,000 had private insurance and/or high family income. Across
      census tracts, average met need was 59% for low-income children and 96% for high
      income children; for rural census tracts, these values were 33% and 84%,
      respectively. The average 1-way travel distance for all census tracts was 3.7
      miles for high-income and/or privately insured children and 17.2 miles for low
      income children; for rural census tracts, these values were 11.6 and 32.9 miles,
      respectively. Increasing dentists' acceptance of public insurance-eligible
      children increased met need more in rural areas than in urban areas. To achieve
      100% met need in rural tracts, however, an 80% participation rate among dentists
      would be required. CONCLUSION: Across census tracts, high-income children had
      better access to preventive dental care than low-income children had. Identifying
      tracts with disparities in access could result in more efficient allocation of
      public health dental resources.

PMID- 29072987
TI  - Can surgical site infections be reduced with the adoption of a bundle of
      simultaneous initiatives? The use of NSQIP incidence data to follow multiple
      quality improvement interventions.
AB  - SUMMARY: Surgical site infections (SSI) are a common complication after surgical
      procedures. To reduce the incidence of SSIs, Oakville Trafalgar Memorial Hospital
      decided to institute a bundle of initiatives to change multiple factors
      simultaneously based on best available evidence and the understanding of
      infection pathophysiology. We used National Surgical Quality Improvement Program
      data on the incidence of SSIs in our targeted and essentials, general surgery and
      orthopedic surgery cases before and after the implementation of an SSI reduction
      bundle. This article discusses whether the use of intervention bundles may assist
      in the reduction of a variety of postoperative surgical complications.

PMID- 29072985
TI  - Electronic Information Standards to Support Obesity Prevention and Bridge
      Services Across Systems, 2010-2015.
AB  - Electronic information technology standards facilitate high-quality, uniform
      collection of data for improved delivery and measurement of health care services.
      Electronic information standards also aid information exchange between secure
      systems that link health care and public health for better coordination of
      patient care and better-informed population health improvement activities. We
      developed international data standards for healthy weight that provide common
      definitions for electronic information technology. The standards capture healthy
      weight data on the "ABCDs" of a visit to a health care provider that addresses
      initial obesity prevention and care: assessment, behaviors, continuity, identify
      resources, and set goals. The process of creating healthy weight standards
      consisted of identifying needs and priorities, developing and harmonizing
      standards, testing the exchange of data messages, and demonstrating use-cases.
      Healthy weight products include 2 message standards, 5 use-cases, 31 LOINC
      (Logical Observation Identifiers Names and Codes) question codes, 7 healthy
      weight value sets, 15 public-private engagements with health information
      technology implementers, and 2 technical guides. A logic model and action steps
      outline activities toward better data capture, interoperable systems, and
      information use. Sharing experiences and leveraging this work in the context of
      broader priorities can inform the development of electronic information standards
      for similar core conditions and guide strategic activities in electronic systems.

PMID- 29072988
TI  - In sickness and in health, till death do us part: Is the ICD a lifelong
      commitment?
AB  - The decision-making process around initial implantation of an Implantable
      Cardioverter Defibrillator (ICD) is well studied, guided by randomized clinical
      trials which have translated into widely accepted clinical guidelines. For
      patients who out-live their first device and are eligible for a generator
      exchange (GE) the indications to replace the battery is much less well-defined.
      In this latter case, the clinician needs to make the decision based on persistent
      indications for primary prevention ICD, risk of future arrhythmic death in the
      absence of ongoing indications for primary prevention, competing causes of non
      arrhythmic death and the patient's overall goals of care.

PMID- 29072983
TI  - Tobacco Use Cessation Among Quitline Callers Who Implemented Complete Home
      Smoking Bans During the Quitting Process.
AB  - INTRODUCTION: The implementation of a home smoking ban (HSB) is associated with
      tobacco use cessation. We identified which quitline callers were most likely to
      report 30-day cessation among those who implemented complete HSBs after
      enrollment. METHODS: Our sample consisted of callers to the Arizona Smokers'
      Helpline who enrolled from January 1, 2011, through July 26, 2015, and who
      reported no HSB at enrollment and a complete HSB by 7-month follow-up. We used
      logistic regression to estimate associations between no use of tobacco in the
      previous 30 days (30-day quit) at 7-month follow-up and demographic
      characteristics, health conditions, tobacco use, and cessation strategies.
      RESULTS: At 7-month follow-up, 65.4% of 399 callers who implemented a complete
      HSB reported 30-day quit. Lower odds of tobacco use cessation were associated
      with having a chronic health condition (odds ratio [OR], 0.31; 95% confidence
      interval [CI], 0.18-0.56) and living with other smokers (OR, 0.46; 95% CI, 0.29
      0.73). Higher odds of tobacco cessation were associated with completing 5 or more
      telephone coaching sessions (OR, 2.48; 95% CI, 1.54-3.98) and having confidence
      to quit (OR, 2.05; 95% CI, 1.05-3.99). However, confidence to quit was not
      significant in the sensitivity analysis. CONCLUSION: Implementing an HSB after
      enrolling in quitline services increases the likelihood of cessation among some
      tobacco users. Individuals with complete HSBs were more likely to quit if they
      did not have a chronic health condition, did not live with another smoker, and
      were actively engaged in coaching services. These findings may be used by
      quitlines to develop HSB intervention protocols primarily targeting tobacco users
      most likely to benefit from them.

PMID- 29072986
TI  - Parity and Overweight/Obesity in Peruvian Women.
AB  - INTRODUCTION: The rise in noncommunicable diseases and their risk factors in
      developing countries may have changed or intensified the effect of parity on
      obesity. We aimed to assess this association in Peruvian women using data from a
      nationally representative survey. METHODS: We used data from Peru's Demographic
      and Health Survey, 2012. Parity was defined as the number of children ever born
      to a woman. We defined overweight as having a body mass index (BMI, kg/m2) of
      25.0 to 29.9 and obesity as a BMI >=30.0. Generalized linear models were used to
      evaluate the association between parity and BMI and BMI categories, by area of
      residence and age, adjusting for confounders. RESULTS: Data from 16,082 women
      were analyzed. Mean parity was 2.25 (95% confidence interval [CI], 2.17-2.33)
      among rural women and 1.40 (95% CI, 1.36-1.43) among urban women. Mean BMI was
      26.0 (standard deviation, 4.6). We found evidence of an association between
      parity and BMI, particularly in younger women; BMI was up to 4 units higher in
      rural areas and 2 units higher in urban areas. An association between parity and
      BMI categories was observed in rural areas as a gradient, being highest in
      younger women. CONCLUSION: We found a positive association between parity and
      overweight/obesity. This relationship was stronger in rural areas and among
      younger mothers.

PMID- 29072990
TI  - AF ablation: Single shot multielectrode or multishot single electrode?

PMID- 29072989
TI  - Persistence of ICD indication at the time of replacement in patients with initial
      implant for primary prevention indication: Effect on subsequent ICD therapies.
AB  - BACKGROUND: Indication to implantable cardioverter defibrillator (ICD) for
      primary prevention of sudden death relies on left ventricular ejection fraction
      (LVEF). We measured the proportion of patients in whom indication to ICD
      persisted at the time of generator replacement (GR) and searched for predictors
      of appropriate therapies after GR. METHODS: We identified all consecutive
      patients who had received an ICD at our hospital, for LVEF <=35% and no previous
      arrhythmias or unexplained syncope. Then, we included the 166 patients who
      outlived their first device and underwent GR. RESULTS: At the time of GR (mean
      follow-up 59 +/- 20 months), ICD indication (i.e. LVEF <=35% or previously
      treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR,
      appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD
      indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless,
      the annual rate of therapies was higher in the first group (1.08 versus 0.53
      events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03
      versus 0 events/year; p = 0.031). The only independent predictor of appropriate
      ICD therapies after GR was the rate of shocks received before replacement (Hazard
      Ratio: 1.41; 95% confidence interval: 1.01-1.96; p = 0.041). CONCLUSION: In heart
      failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of
      patients. However, even in the absence of persistent ICD indication at GR, the
      risk of recurrence of arrhythmic events was not null.

PMID- 29072992
TI  - Low-energy cardioversion of ventricular tachycardia: When less is more.
AB  - Herein we report the case of a patient who was admitted in ventricular
      tachycardia after having received multiple ineffective (and sometimes pro
      arrhythmic) high-energy internal shocks from his ICD and who was finally
      successfully treated by a commanded low-energy internal cardioversion of 0.6 J.
      This article revisits the use of low-energy shocks and discusses their
      electrophysiogical mechanisms and clinical implications.

PMID- 29072993
TI  - Tilted ECG - An unusual tilt test response.
AB  - Tilt testing is a commonly used diagnostic tool to evaluate syncope of
      undetermined etiology. We hereby describe a twelve year old male child who
      developed presyncope during provocative head up tilt testing along with ST
      segment elevation in cardiac monitor during presyncope. Patient underwent repeat
      head up tilt testing along with holter monitoring which showed a left bundle
      branch block escape rhythm. Hence development of ST elevation was due to the
      improper filter application in single lead ECG monitor. This case highlights the
      importance of filters in electrocardiographic monitoring.

PMID- 29072994
TI  - Aborted sudden cardiac death in a patient with implantable loop recorder.
AB  - We discuss a 46-year-old man with history of hypertension and inferior wall
      myocardial infarction and mild left ventricular dysfunction who presented with
      aborted sudden cardiac death due to episodes of ventricular tachyarrhythmia
      detected by a Reveal-LINQ which had been implanted one year prior to
      presentation.

PMID- 29072991
TI  - Pulmonary vein isolation using multi-electrode radiofrequency vs conventional
      point-by-point radiofrequency ablation: A meta-analysis of randomized and non
      randomized studies.
AB  - AIMS: Pulmonary vein isolation is effective in reducing atrial fibrillation (AF)
      episodes. Previous studies suggest single-shot techniques are effective and safe
      for this purpose. Procedural and clinical outcomes were compared between multi
      electrode and point-by-point radiofrequency ablations by performing a meta
      analysis of all randomized and non-randomized studies. METHODS AND RESULTS:
      Systematic reviews of MEDLINE and Cochrane Library databases were performed.
      Studies comparing procedural (procedure and fluoroscopy times) and clinical (AF
      recurrence) outcomes were included in the meta-analysis. A total of 13 clinical
      studies (5 randomized and 8 non-randomized) including 2152 patients met the
      inclusion criteria. In patients underwent multi-electrode ablation, there were
      significant reductions in both total procedure and fluoroscopy times, compared
      with point-by-point ablation (mean difference = -34.3 min [95% CI (-50.1 to 
      18.5)], p < 0.001 and mean difference = -7.1 min [95% CI (-12.0 to -2.2)], p <
      0.01, respectively). These significances also continued in patients with
      paroxysmal AF. No such difference was observed in regard to AF recurrence between
      the 2 ablation strategies (RR = 0.90 [95% CI (0.80-1.01)], p = 0.066). This
      insignificance was also observed in patients with paroxysmal AF. CONCLUSIONS: In
      a heterogeneous AF population, multi-electrode ablation is as effective as point
      by-point ablation, with better procedural and fluoroscopy durations.

PMID- 29072995
TI  - Which side are you on? - Deducing the chamber of origin of atrial tachycardia.
AB  - Atrial arrhythmias rising from the regions of the atria that are in close
      proximity to each other may pose a challenge in identifying the chamber to map
      and ablate in. In this report, we discuss a patient with left atrial tachycardia
      which initially mimicked right atrial tachycardia. We discuss the origins of the
      abnormal electrograms in the right atrium and how this provides a general
      understanding of the mechanism of double potentials.

PMID- 29072996
TI  - Wide QRS tachycardia in a patient with pre excitation; what are the pathways
      involved? Pacing manoeuvres to characterize a unique pathway.
AB  - A 30year old patient presented to us with recurrent episodes of palpitation and
      documented tachycardia. In all his presentations a wide QRS tachycardia was
      recorded. The baseline ECG showed pre excitation. The 12 lead ECG of the
      tachycardia and the baseline ECG is shown in Fig. 1A. During EP study the patient
      had baseline pre excitation and the HV interval was 16 ms. A duo-decapolar halo
      (HL) catheter was used to map right atrium and a decapolar coronary sinus (CS)
      catheter was used to map coronary sinus. In addition a His bundle and right
      ventricular (RV) quadripolar catheters were used. The delta wave morphology was
      suggestive of a posteroseptal pathway. Ventricular pacing from RV apex showing
      central decremental conduction with ventriculo-atrial Wenkebach at 290 ms.
      Ventricular extrastimulation also showed decremental conduction and VA block at
      S1 S2 of 400,240. The intra cardiac recording of tachycardia and its initiation
      is shown in Fig. 1B. Pacing from lateral RA (HL 5, 6 electrodes) showed
      progressive pre excitation with extrastimulation and induction of tachycardia.
      The QRS morphology was same as the patient's clinical tachycardia and the
      tachycardia cycle length (TCL) was 304 ms. An atrial entrainment protocol showed
      entrainment with the same QRS morphology while pacing from right atrium. The VA
      interval of the first return cycle was the same as the subsequent VA intervals. A
      ventricular entrainment protocol showed V-A-V response and post pacing interval
      of 414 ms. An atrial extra systole was given from the mid CS electrodes (CS 5, 6)
      - the effect is shown in Fig. 3. In sinus rhythm a parahisian pacing manoeuvre
      was done as shown in Fig. 4A. What is the mechanism of the tachycardia and what
      are the pathways involved?

PMID- 29072997
TI  - How good is your life vest in the real world?

PMID- 29072998
TI  - Real world utilization and impact of the wearable cardioverter-defibrillator in a
      community setting.
AB  - INTRODUCTION: The wearable cardioverter-defibrillator (WCD) is used in patients
      at risk for sudden cardiac death (SCD) but not immediate candidates for
      intracardiac defibrillator (ICD) implantation. METHODS: We performed a single
      center retrospective study of patients prescribed WCD upon hospital discharge
      from January 2002 to October 2015. Clinical characteristics were obtained from
      the hospital electronic database and device data from Zoll LifeVest database.
      RESULTS: Of 140 patients, 62% were men, 85.9% were African-American and mean age
      was 58.2 +/- 15.5 years. Ischemic cardiomyopathy was present in 45 (32%) and non
      ischemic cardiomyopathy in 64 patients (46%). Mean left ventricular ejection
      fraction (EF) was 0.28 +/- 0.4. WCD was worn for 7657 patient-days (21 patient
      years), with each patient using WCD for median of 43 days (IQR: 7-83 days), and
      daily mean use 17.3 +/- 7.5 h. There were a total of 6 (4.2%) WCD shocks of which
      2 (1.4%) were appropriate (one for VT, one for VF) and 4 (2.8%) were
      inappropriate (2 had supraventricular tachycardia, 2 had artifact). Two patients
      who received appropriate shocks were African-American with non-ischemic
      cardiomyopathy (EF<20%), non-sustained VT and wide QRS duration. Upon termination
      of WCD use, 45 (32%) received ICD while EF improved in 34 patients (32%).
      CONCLUSIONS: In a predominantly minority, community setting, WCD compliance is
      high and use is effective in aborting SCD. However, inappropriate shocks do
      occur. A significant proportion of patients did not ultimately require ICD
      implantation suggesting this may be a cost-effective strategy in patients at risk
      of SCD.

PMID- 29072999
TI  - When limited by cost in CRT-be a leftist!

PMID- 29073002
TI  - An atypical mechanism of pseudo mitral isthmus block clarified by the high
      resolution mapping system.

PMID- 29073001
TI  - Kearns Sayre Syndrome: Looking beyond A-V conduction.
AB  - A 15-year-old boy was diagnosed with Kayne Sayre Syndrome. He presented with
      pigmentary retinopathy, progressive ophthalmoplegia and complete heart block. He
      received a transvenous dual chamber pacemaker. Two years later he died suddenly
      while at home. This case highlights the importance of recognizing mechanisms
      other than heart block as a cause of sudden death in a patient with KSS.

PMID- 29073000
TI  - 'Optimized' LV only pacing using a dual chamber pacemaker as a cost effective
      alternative to CRT.
AB  - BACKGROUND: Cardiac Resynchronization therapy (CRT) remains largely under-used in
      developing countries owing to the high cost of therapy. In this pilot study, we
      explore 'optimized' Left Ventricle Only Pacing (LVOP) as a cost effective
      alternative to cardiac resynchronization therapy in selected patients with heart
      failure. HYPOTHESIS: In economically poorer patients with heart failure, left
      bundle branch block (LBBB) and intact AV node conduction, synchronization can be
      obtained using a dual chamber pacemaker (leads in right atrium and Left
      ventricle) with the help of 2D strain imaging. METHODS AND RESULTS: 4 patients
      underwent LVOP for symptomatic heart failure. Post procedure 'optimization' was
      done using 12 lead electrocardiography and 2D- Strain imaging. Difference between
      Time to Peak longitudinal strain and Aortic valve Closure (Diff TPL-AC) was
      calculated for each segment at different AV delays and the AV delay with the
      smallest Diff TPL-AC was programmed. The mean AV delay that resulted in
      electrical and mechanical synchrony was 150 ms. After a mean follow up of 6
      months, all patients had improved by at least 1 NYHA class. The mean reduction in
      QRS duration post procedure was -54.5 +/- 22.82 ms and the mean improvement in EF
      was 7 +/- 2.75%. CONCLUSION: Optimized LVOP using 2D strain and ECG can be a cost
      effective alternative to CRT in patients with LBBB, heart failure and normal AV
      node conduction.

PMID- 29073003
TI  - Unusual induction of a very slow supraventricular tachycardia: What is the
      mechanism?

PMID- 29073004
TI  - P-wave dispersion measurement: Methodological considerations.
AB  - Well-known difficulties in defining P-wave onset and offset may restrict the
      accuracy and reproducibility of P-wave dispersion measurements. To achieve
      greater precision in measuring P-wave dispersion, simultaneous digital recording
      of all 12 ECG leads and onscreen measurement of P wave characteristics is
      mandatory to examine atrial fibrillation risk.

PMID- 29073005
TI  - Inner Workings: CubeSats set to tackle living systems, effects of deep space
      radiation.

PMID- 29073007
TI  - Studying folktale diffusion needs unbiased dataset.

PMID- 29073008
TI  - Reply to d'Huy et al.: Navigating biases and charting new ground in the cultural
      diffusion of folktales.

PMID- 29073009
TI  - Opinion: Fostering synthesis in archaeology to advance science and benefit
      society.

PMID- 29073010
TI  - Profile of Lora V. Hooper.

PMID- 29073011
TI  - Synthetic genome engineering gets infectious.

PMID- 29073012
TI  - Trees harness the power of microbes to survive climate change.

PMID- 29073013
TI  - NS1 is the fluid for "flu-transmission".

PMID- 29073015
TI  - Mechanically switching single-molecule fluorescence of GFP by unfolding and
      refolding.
AB  - Green fluorescent protein (GFP) variants are widely used as genetically encoded
      fluorescent fusion tags, and there is an increasing interest in engineering their
      structure to develop in vivo optical sensors, such as for optogenetics and force
      transduction. Ensemble experiments have shown that the fluorescence of GFP is
      quenched upon denaturation. Here we study the dependence of fluorescence on
      protein structure by driving single molecules of GFP into different
      conformational states with optical tweezers and simultaneously probing the
      chromophore with fluorescence. Our results show that fluorescence is lost during
      the earliest events in unfolding, 3.5 ms before secondary structure is disrupted.
      No fluorescence is observed from the unfolding intermediates or the ensemble of
      compact and extended states populated during refolding. We further demonstrate
      that GFP can be mechanically switched between emissive and dark states. These
      data definitively establish that complete structural integrity is necessary to
      observe single-molecule fluorescence of GFP.

PMID- 29073016
TI  - Allocating dissipation across a molecular machine cycle to maximize flux.
AB  - Biomolecular machines consume free energy to break symmetry and make directed
      progress. Nonequilibrium ATP concentrations are the typical free energy source,
      with one cycle of a molecular machine consuming a certain number of ATP,
      providing a fixed free energy budget. Since evolution is expected to favor rapid
      turnover machines that operate efficiently, we investigate how this free energy
      budget can be allocated to maximize flux. Unconstrained optimization eliminates
      intermediate metastable states, indicating that flux is enhanced in molecular
      machines with fewer states. When maintaining a set number of states, we show that
      in contrast to previous findings-the flux-maximizing allocation of dissipation is
      not even. This result is consistent with the coexistence of both "irreversible"
      and reversible transitions in molecular machine models that successfully describe
      experimental data, which suggests that, in evolved machines, different
      transitions differ significantly in their dissipation.

PMID- 29073017
TI  - Direct measurement of weakly nonequilibrium system entropy is consistent with
      Gibbs-Shannon form.
AB  - Stochastic thermodynamics extends classical thermodynamics to small systems in
      contact with one or more heat baths. It can account for the effects of thermal
      fluctuations and describe systems far from thermodynamic equilibrium. A basic
      assumption is that the expression for Shannon entropy is the appropriate
      description for the entropy of a nonequilibrium system in such a setting. Here we
      measure experimentally this function in a system that is in local but not global
      equilibrium. Our system is a micron-scale colloidal particle in water, in a
      virtual double-well potential created by a feedback trap. We measure the work to
      erase a fraction of a bit of information and show that it is bounded by the
      Shannon entropy for a two-state system. Further, by measuring directly the
      reversibility of slow protocols, we can distinguish unambiguously between
      protocols that can and cannot reach the expected thermodynamic bounds.

PMID- 29073018
TI  - Minimal and RNA-free RNase P in Aquifex aeolicus.
AB  - RNase P is an essential tRNA-processing enzyme in all domains of life. We
      identified an unknown type of protein-only RNase P in the hyperthermophilic
      bacterium Aquifex aeolicus: Without an RNA subunit and the smallest of its kind,
      the 23-kDa polypeptide comprises a metallonuclease domain only. The protein has
      RNase P activity in vitro and rescued the growth of Escherichia coli and
      Saccharomyces cerevisiae strains with inactivations of their more complex and
      larger endogenous ribonucleoprotein RNase P. Homologs of Aquifex RNase P (HARP)
      were identified in many Archaea and some Bacteria, of which all Archaea and most
      Bacteria also encode an RNA-based RNase P; activity of both RNase P forms from
      the same bacterium or archaeon could be verified in two selected cases.
      Bioinformatic analyses suggest that A. aeolicus and related Aquificaceae likely
      acquired HARP by horizontal gene transfer from an archaeon.

PMID- 29073019
TI  - Structure and dynamics of the RNAPII CTDsome with Rtt103.
AB  - RNA polymerase II contains a long C-terminal domain (CTD) that regulates
      interactions at the site of transcription. The CTD architecture remains poorly
      understood due to its low sequence complexity, dynamic phosphorylation patterns,
      and structural variability. We used integrative structural biology to visualize
      the architecture of the CTD in complex with Rtt103, a 3'-end RNA-processing and
      transcription termination factor. Rtt103 forms homodimers via its long coiled
      coil domain and associates densely on the repetitive sequence of the
      phosphorylated CTD via its N-terminal CTD-interacting domain. The CTD-Rtt103
      association opens the compact random coil structure of the CTD, leading to a
      beads-on-a-string topology in which the long rod-shaped Rtt103 dimers define the
      topological and mobility restraints of the entire assembly. These findings
      underpin the importance of the structural plasticity of the CTD, which is
      templated by a particular set of CTD-binding proteins.

PMID- 29073020
TI  - Tectonic conformational changes of a coronavirus spike glycoprotein promote
      membrane fusion.
AB  - The tremendous pandemic potential of coronaviruses was demonstrated twice in the
      past few decades by two global outbreaks of deadly pneumonia. The coronavirus
      spike (S) glycoprotein initiates infection by promoting fusion of the viral and
      cellular membranes through conformational changes that remain largely
      uncharacterized. Here we report the cryoEM structure of a coronavirus S
      glycoprotein in the postfusion state, showing large-scale secondary, tertiary,
      and quaternary rearrangements compared with the prefusion trimer and
      rationalizing the free-energy landscape of this conformational machine. We also
      biochemically characterized the molecular events associated with refolding of the
      metastable prefusion S glycoprotein to the postfusion conformation using limited
      proteolysis, mass spectrometry, and single-particle EM. The observed similarity
      between postfusion coronavirus S and paramyxovirus F structures demonstrates that
      a conserved refolding trajectory mediates entry of these viruses and supports the
      evolutionary relatedness of their fusion subunits. Finally, our data provide a
      structural framework for understanding the mode of neutralization of antibodies
      targeting the fusion machinery and for engineering next-generation subunit
      vaccines or inhibitors against this medically important virus family.

PMID- 29073022
TI  - Surfing of bacterial droplets: Bacillus subtilis sliding revisited.

PMID- 29073021
TI  - Multigenerational silencing dynamics control cell aging.
AB  - Cellular aging plays an important role in many diseases, such as cancers,
      metabolic syndromes, and neurodegenerative disorders. There has been steady
      progress in identifying aging-related factors such as reactive oxygen species and
      genomic instability, yet an emerging challenge is to reconcile the contributions
      of these factors with the fact that genetically identical cells can age at
      significantly different rates. Such complexity requires single-cell analyses
      designed to unravel the interplay of aging dynamics and cell-to-cell variability.
      Here we use microfluidic technologies to track the replicative aging of single
      yeast cells and reveal that the temporal patterns of heterochromatin silencing
      loss regulate cellular life span. We found that cells show sporadic waves of
      silencing loss in the heterochromatic ribosomal DNA during the early phases of
      aging, followed by sustained loss of silencing preceding cell death. Isogenic
      cells have different lengths of the early intermittent silencing phase that
      largely determine their final life spans. Combining computational modeling and
      experimental approaches, we found that the intermittent silencing dynamics is
      important for longevity and is dependent on the conserved Sir2 deacetylase,
      whereas either sustained silencing or sustained loss of silencing shortens life
      span. These findings reveal that the temporal patterns of a key molecular process
      can directly influence cellular aging, and thus could provide guidance for the
      design of temporally controlled strategies to extend life span.

PMID- 29073023
TI  - Reply to Kovacs et al.: Surfing or sliding: The act of naming and its
      implications.

PMID- 29073024
TI  - Purported fragile-to-Arrhenius crossover in squalane.

PMID- 29073025
TI  - Reply to Bair: Crossover to Arrhenius behavior at high viscosities in squalane.

PMID- 29073026
TI  - No experimental Fermi surface measurements have been reported or made on low
      temperature martensitic lithium.

PMID- 29073027
TI  - Reply to Martinez-Canales et al.: The structure(s) of lithium at low
      temperatures.

PMID- 29073028
TI  - Evolutionary dynamics of language systems.
AB  - Understanding how and why language subsystems differ in their evolutionary
      dynamics is a fundamental question for historical and comparative linguistics.
      One key dynamic is the rate of language change. While it is commonly thought that
      the rapid rate of change hampers the reconstruction of deep language
      relationships beyond 6,000-10,000 y, there are suggestions that grammatical
      structures might retain more signal over time than other subsystems, such as
      basic vocabulary. In this study, we use a Dirichlet process mixture model to
      infer the rates of change in lexical and grammatical data from 81 Austronesian
      languages. We show that, on average, most grammatical features actually change
      faster than items of basic vocabulary. The grammatical data show less
      schismogenesis, higher rates of homoplasy, and more bursts of contact-induced
      change than the basic vocabulary data. However, there is a core of grammatical
      and lexical features that are highly stable. These findings suggest that
      different subsystems of language have differing dynamics and that careful,
      nuanced models of language change will be needed to extract deeper signal from
      the noise of parallel evolution, areal readaptation, and contact.

PMID- 29073029
TI  - Visualizing nuclear RNAi activity in single living human cells.
AB  - Nuclear RNA interference (RNAi) is mediated by the canonical RNAi machinery and
      can lead to transcriptional silencing, transcriptional activation, or modulation
      of alternative splicing patterns. These effects transpire through changes in
      histone and DNA modifications via RNAi-mediated recruitment of chromatin
      modifying enzymes. To prove that nuclear RNAi occurs and modulates transcription
      in human cells, we used live-cell imaging to detect and track nuclear RNAi
      transcriptional repression in single living human cells. While employing reporter
      genes constructed with inducible promoters and cognate-inducible short hairpin
      RNA (shRNA) targeted against the reporter coding region, we have characterized
      the dynamics of the nuclear RNAi process in living human cells. We show that the
      silencing effect is mediated through the nascent mRNA, followed by activity of
      histone methylating enzymes, but not through DNA methylation.

PMID- 29073032
TI  - Correction for Dixon et al., Combined hydrogels that switch human pluripotent
      stem cells from self-renewal to differentiation.

PMID- 29073030
TI  - Expanded subgenomic mRNA transcriptome and coding capacity of a nidovirus.
AB  - Members of the order Nidovirales express their structural protein ORFs from a
      nested set of 3' subgenomic mRNAs (sg mRNAs), and for most of these ORFs, a
      single genomic transcription regulatory sequence (TRS) was identified. Nine TRSs
      were previously reported for the arterivirus Simian hemorrhagic fever virus
      (SHFV). In the present study, which was facilitated by next-generation
      sequencing, 96 SHFV body TRSs were identified that were functional in both
      infected MA104 cells and macaque macrophages. The abundance of sg mRNAs produced
      from individual TRSs was consistent over time in the two different cell types.
      Most of the TRSs are located in the genomic 3' region, but some are in the 5'
      ORF1a/1b region and provide alternative sources of nonstructural proteins.
      Multiple functional TRSs were identified for the majority of the SHFV 3' ORFs,
      and four previously identified TRSs were found not to be the predominant ones
      used. A third of the TRSs generated sg mRNAs with variant leader-body junction
      sequences. Sg mRNAs encoding E', GP2, or ORF5a as their 5' ORF as well as sg
      mRNAs encoding six previously unreported alternative frame ORFs or 14 previously
      unreported C-terminal ORFs of known proteins were also identified. Mutation of
      the start codon of two C-terminal ORFs in an infectious clone reduced virus
      yield. Mass spectrometry detected one previously unreported protein and suggested
      translation of some of the C-terminal ORFs. The results reveal the complexity of
      the transcriptional regulatory mechanism and expanded coding capacity for SHFV,
      which may also be characteristic of other nidoviruses.

PMID- 29073031
TI  - Structures of human-infecting Thogotovirus fusogens support a common ancestor
      with insect baculovirus.
AB  - Thogotoviruses are emerging tick-borne zoonotic orthomyxoviruses infecting both
      humans and domestic animals with severe clinical consequences. These viruses
      utilize a single-envelope glycoprotein (Gp) to facilitate their entry into host
      cells. Here, we present the Gp structures of Thogoto and Dhori viruses, both of
      which are members of the Thogotovirus genus in the family Orthomyxoviridae These
      structures, determined in the postfusion conformation, identified them as class
      III viral fusion proteins. It is intriguing that the Gp structures are similar to
      the envelope protein of baculovirus, although sharing a low sequence identity of
      ~28%. Detailed structural and phylogenic analyses demonstrated that these Gps
      originated from a common ancestor. Among the structures, domain I is the most
      conserved region, particularly the fusion loops. Domain II showed the highest
      variability among different viruses, which might be related to their distinct
      host tropism. These findings increase our understanding of the divergent
      evolution processes of various orthomyxoviruses and indicate potential targets
      for developing antiviral therapeutics by intercepting virus entry.

PMID- 29073033
TI  - Correction for Cekanaviciute et al., Gut bacteria from multiple sclerosis
      patients modulate human T cells and exacerbate symptoms in mouse models.

PMID- 29073034
TI  - Correction to Supporting Information for Palermo et al., CRISPR-Cas9
      conformational activation as elucidated from enhanced molecular simulations.

PMID- 29073035
TI  - Science and Culture: Vegetable breeders turn to chefs for flavor boost.

PMID- 29073036
TI  - Core Concepts: How diversity-generating retroelements promote mutation and
      adaptation in myriad microbes.

PMID- 29073039
TI  - Core Concept: Circumventing the blood-brain barrier.

PMID- 29073038
TI  - Actin retrograde flow actively aligns and orients ligand-engaged integrins in
      focal adhesions.
AB  - Integrins are transmembrane receptors that, upon activation, bind extracellular
      ligands and link them to the actin filament (F-actin) cytoskeleton to mediate
      cell adhesion and migration. Cytoskeletal forces in migrating cells generated by
      polymerization- or contractility-driven "retrograde flow" of F-actin from the
      cell leading edge have been hypothesized to mediate integrin activation for
      ligand binding. This predicts that these forces should align and orient
      activated, ligand-bound integrins at the leading edge. Here, polarization
      sensitive fluorescence microscopy of GFP-alphaVbeta3 integrins in fibroblasts
      shows that integrins are coaligned in a specific orientation within focal
      adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin
      mediated linkage to the F-actin cytoskeleton. These findings, together with
      Rosetta modeling, suggest that integrins in FA are coaligned and may be highly
      tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an
      anisotropic molecular scaffold in FAs, and this feature may underlie the ability
      of migrating cells to sense directional extracellular cues.

PMID- 29073040
TI  - Darwin's prescient guess.

PMID- 29073041
TI  - Lipid sorting and the activity of Arf signaling complexes.

PMID- 29073042
TI  - Compartmentalized dendritic signaling in a multitasking retinal interneuron.

PMID- 29073045
TI  - Distinct ice patterns on solid surfaces with various wettabilities.
AB  - No relationship has been established between surface wettability and ice growth
      patterns, although ice often forms on top of solid surfaces. Here, we report
      experimental observations obtained using a process specially designed to avoid
      the influence of nucleation and describe the wettability-dependent ice morphology
      on solid surfaces under atmospheric conditions and the discovery of two growth
      modes of ice crystals: along-surface and off-surface growth modes. Using
      atomistic molecular dynamics simulation analysis, we show that these distinct ice
      growth phenomena are attributable to the presence (or absence) of bilayer ice on
      solid surfaces with different wettability; that is, the formation of bilayer ice
      on hydrophilic surface can dictate the along-surface growth mode due to the
      structural match between the bilayer hexagonal ice and the basal face of
      hexagonal ice (ice Ih), thereby promoting rapid growth of nonbasal faces along
      the hydrophilic surface. The dramatically different growth patterns of ice on
      solid surfaces are of crucial relevance to ice repellency surfaces.

PMID- 29073044
TI  - SMELL-S and SMELL-R: Olfactory tests not influenced by odor-specific
      insensitivity or prior olfactory experience.
AB  - Smell dysfunction is a common and underdiagnosed medical condition that can have
      serious consequences. It is also an early biomarker of neurodegenerative
      diseases, including Alzheimer's disease, where olfactory deficits precede
      detectable memory loss. Clinical tests that evaluate the sense of smell face two
      major challenges. First, human sensitivity to individual odorants varies
      significantly, so test results may be unreliable in people with low sensitivity
      to a test odorant but an otherwise normal sense of smell. Second, prior
      familiarity with odor stimuli can bias smell test performance. We have developed
      nonsemantic tests for olfactory sensitivity (SMELL-S) and olfactory resolution
      (SMELL-R) that use mixtures of odorants that have unfamiliar smells. The tests
      can be self-administered by healthy individuals with minimal training and show
      high test-retest reliability. Because SMELL-S uses odor mixtures rather than a
      single molecule, odor-specific insensitivity is averaged out, and the test
      accurately distinguished people with normal and dysfunctional smell. SMELL-R is a
      discrimination test in which the difference between two stimulus mixtures can be
      altered stepwise. This is an advance over current discrimination tests, which ask
      subjects to discriminate monomolecular odorants whose difference in odor cannot
      be quantified. SMELL-R showed significantly less bias in scores between North
      American and Taiwanese subjects than conventional semantically based smell tests
      that need to be adapted to different languages and cultures. Based on these proof
      of-principle results in healthy individuals, we predict that SMELL-S and SMELL-R
      will be broadly effective in diagnosing smell dysfunction.

PMID- 29073046
TI  - Nonequilibrium fluctuations of lipid membranes by the rotating motor protein F1F0
      ATP synthase.
AB  - ATP synthase is a rotating membrane protein that synthesizes ATP through proton
      pumping activity across the membrane. To unveil the mechanical impact of this
      molecular active pump on the bending properties of its lipid environment, we have
      functionally reconstituted the ATP synthase in giant unilamellar vesicles and
      tracked the membrane fluctuations by means of flickering spectroscopy. We find
      that ATP synthase rotates at a frequency of about 20 Hz, promoting large
      nonequilibrium deformations at discrete hot spots in lipid vesicles and thus
      inducing an overall membrane softening. The enhanced nonequilibrium fluctuations
      are compatible with an accumulation of active proteins at highly curved membrane
      sites through a curvature-protein coupling mechanism that supports the emergence
      of collective effects of rotating ATP synthases in lipid membranes.

PMID- 29073047
TI  - Semiconductor quantum dot-sensitized rainbow photocathode for effective
      photoelectrochemical hydrogen generation.
AB  - The present study reports the fabrication of CdSe quantum dot (QD)-sensitized
      photocathodes on NiO-coated indium tin oxide (ITO) electrodes and their H2
      generating ability upon light irradiation. A well-established spin-coating method
      was used to deposit CdSe QD stock solution onto the surface of NiO/ITO
      electrodes, thereby leading to the construction of various CdSe QD-sensitized
      photocathodes. The present report includes the construction of rainbow
      photocathodes by spin-coating different-sized QDs in a sequentially layered
      manner, thereby creating an energetically favorable gradient for charge
      separation. The resulting rainbow photocathodes with forward energetic gradient
      for charge separation and subsequent electron transfer to a solution-based
      hydrogen-evolving catalyst (HEC) exhibit good light-harvesting ability and
      enhanced photoresponses compared with the reverse rainbow photocathodes under
      white LED light illumination. Under minimally optimized conditions, a
      photocurrent density of as high as 115 MUA?cm-2 and a Faradaic efficiency of
      99.5% are achieved, which is among the most effective QD-based photocathode water
      splitting systems.

PMID- 29073048
TI  - Multielectron, multisubstrate molecular catalysis of electrochemical reactions:
      Formal kinetic analysis in the total catalysis regime.
AB  - Cyclic voltammetry responses are derived for two-electron, two-step homogeneous
      electrocatalytic reactions in the total catalysis regime. The models developed
      provide a framework for extracting kinetic information from cyclic voltammograms
      (CVs) obtained in conditions under which the substrate or cosubstrate is consumed
      in a multielectron redox process, as is particularly prevalent for very active
      catalysts that promote energy conversion reactions. Such determination of rate
      constants in the total catalysis regime is a prerequisite for the rational
      benchmarking of molecular electrocatalysts that promote multielectron conversions
      of small-molecule reactants. The present analysis is illustrated with
      experimental systems encompassing various limiting behaviors.

PMID- 29073049
TI  - Production of diverse PET probes with limited resources: 24 18F-labeled compounds
      prepared with a single radiosynthesizer.
AB  - New radiolabeled probes for positron-emission tomography (PET) are providing an
      ever-increasing ability to answer diverse research and clinical questions and to
      facilitate the discovery, development, and clinical use of drugs in patient care.
      Despite the high equipment and facility costs to produce PET probes, many
      radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer
      to produce each probe, even if the equipment is idle much of the time, to avoid
      the challenges of reconfiguring the system fluidics to switch from one probe to
      another. To meet growing demand, more cost-efficient approaches are being
      developed, such as radiosynthesizers based on disposable "cassettes," that do not
      require reconfiguration to switch among probes. However, most cassette-based
      systems make sacrifices in synthesis complexity or tolerated reaction conditions,
      and some do not support custom programming, thereby limiting their generality. In
      contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports
      higher temperatures and pressures than other systems while also facilitating
      flexible synthesis development. In this paper, the syntheses of 24 known PET
      probes are adapted to this system to explore the possibility of using a single
      radiosynthesizer and hot cell for production of a diverse array of compounds with
      wide-ranging synthesis requirements, alongside synthesis development efforts.
      Most probes were produced with yields and synthesis times comparable to
      literature reports, and because hardware modification was unnecessary, it was
      convenient to frequently switch among probes based on demand. Although our
      facility supplies probes for preclinical imaging, the same workflow would be
      applicable in a clinical setting.

PMID- 29073050
TI  - Prebiotic stereoselective synthesis of purine and noncanonical pyrimidine
      nucleotide from nucleobases and phosphorylated carbohydrates.
AB  - According to a current "RNA first" model for the origin of life, RNA emerged in
      some form on early Earth to become the first biopolymer to support Darwinism
      here. Threose nucleic acid (TNA) and other polyelectrolytes are also considered
      as the possible first Darwinian biopolymer(s). This model is being developed by
      research pursuing a "Discontinuous Synthesis Model" (DSM) for the formation of
      RNA and/or TNA from precursor molecules that might have been available on early
      Earth from prebiotic reactions, with the goal of making the model less
      discontinuous. In general, this is done by examining the reactivity of isolated
      products from proposed steps that generate those products, with increasing
      complexity of the reaction mixtures in the proposed mineralogical environments.
      Here, we report that adenine, diaminopurine, and hypoxanthine nucleoside
      phosphates and a noncanonical pyrimidine nucleoside (zebularine) phosphate can be
      formed from the direct coupling reaction of cyclic carbohydrate phosphates with
      the free nucleobases. The reaction is stereoselective, giving only the beta
      anomer of the nucleotides within detectable limits. For purines, the coupling is
      also regioselective, giving the N-9 nucleotide for adenine as a major product. In
      the DSM, phosphorylated carbohydrates are presumed to have been available via
      reactions explored previously [Krishnamurthy R, Guntha S, Eschenmoser A (2000)
      Angew Chem Int Ed 39:2281-2285], while nucleobases are presumed to have been
      available from hydrogen cyanide and other nitrogenous species formed in Earth's
      primitive atmosphere.

PMID- 29073051
TI  - Bird specimens track 135 years of atmospheric black carbon and environmental
      policy.
AB  - Atmospheric black carbon has long been recognized as a public health and
      environmental concern. More recently, black carbon has been identified as a
      major, ongoing contributor to anthropogenic climate change, thus making
      historical emission inventories of black carbon an essential tool for assessing
      past climate sensitivity and modeling future climate scenarios. Current estimates
      of black carbon emissions for the early industrial era have high uncertainty,
      however, because direct environmental sampling is sparse before the mid-1950s.
      Using photometric reflectance data of >1,300 bird specimens drawn from natural
      history collections, we track relative ambient concentrations of atmospheric
      black carbon between 1880 and 2015 within the US Manufacturing Belt, a region
      historically reliant on coal and dense with industry. Our data show that black
      carbon levels within the region peaked during the first decade of the 20th
      century. Following this peak, black carbon levels were positively correlated with
      coal consumption through midcentury, after which they decoupled, with black
      carbon concentrations declining as consumption continued to rise. The precipitous
      drop in atmospheric black carbon at midcentury reflects policies promoting
      burning efficiency and fuel transitions rather than regulating emissions alone.
      Our findings suggest that current emission inventories based on predictive
      modeling underestimate levels of atmospheric black carbon for the early
      industrial era, suggesting that the contribution of black carbon to past climate
      forcing may also be underestimated. These findings build toward a spatially
      dynamic emission inventory of black carbon based on direct environmental
      sampling.

PMID- 29073052
TI  - Formation of most of our coal brought Earth close to global glaciation.
AB  - The bulk of Earth's coal deposits used as fossil fuel today was formed from plant
      debris during the late Carboniferous and early Permian periods. The high burial
      rate of organic carbon correlates with a significant drawdown of atmospheric
      carbon dioxide (CO2) at that time. A recent analysis of a high-resolution record
      reveals large orbitally driven variations in atmospheric CO2 concentration
      between [Formula: see text]150 and 700 ppm for the latest Carboniferous and very
      low values of 100 [Formula: see text] 80 ppm for the earliest Permian. Here, I
      explore the sensitivity of the climate around the Carboniferous/Permian boundary
      to changes in Earth's orbital parameters and in atmospheric CO2 using a coupled
      climate model. The coldest orbital configurations are characterized by large
      axial tilt and small eccentricities of Earth's elliptical orbit, whereas the
      warmest configuration occurs at minimum tilt, maximum eccentricity, and a
      perihelion passage during Northern hemisphere spring. Global glaciation occurs at
      CO2 concentrations <40 ppm, suggesting a rather narrow escape from a fully
      glaciated Snowball Earth state given the low levels and large fluctuations of
      atmospheric CO2 These findings highlight the importance of orbital cycles for the
      climate and carbon cycle during the late Paleozoic ice age and the climatic
      significance of the fossil carbon stored in Earth's coal deposits.

PMID- 29073053
TI  - Geophysical potential for wind energy over the open oceans.
AB  - Wind turbines continuously remove kinetic energy from the lower troposphere,
      thereby reducing the wind speed near hub height. The rate of electricity
      generation in large wind farms containing multiple wind arrays is, therefore,
      constrained by the rate of kinetic energy replenishment from the atmosphere
      above. In recent years, a growing body of research argues that the rate of
      generated power is limited to around 1.5 W m-2 within large wind farms. However,
      in this study, we show that considerably higher power generation rates may be
      sustainable over some open ocean areas. In particular, the North Atlantic is
      identified as a region where the downward transport of kinetic energy may sustain
      extraction rates of 6 W m-2 and above over large areas in the annual mean.
      Furthermore, our results indicate that the surface heat flux from the oceans to
      the atmosphere may play an important role in creating regions where sustained
      high rates of downward transport of kinetic energy and thus, high rates of
      kinetic energy extraction may be geophysical possible. While no commercial-scale
      deep water wind farms yet exist, our results suggest that such technologies, if
      they became technically and economically feasible, could potentially provide
      civilization-scale power.

PMID- 29073054
TI  - Resistivity bound for hydrodynamic bad metals.
AB  - We obtain a rigorous upper bound on the resistivity [Formula: see text] of an
      electron fluid whose electronic mean free path is short compared with the scale
      of spatial inhomogeneities. When such a hydrodynamic electron fluid supports a
      nonthermal diffusion process-such as an imbalance mode between different bands-we
      show that the resistivity bound becomes [Formula: see text] The coefficient
      [Formula: see text] is independent of temperature and inhomogeneity lengthscale,
      and [Formula: see text] is a microscopic momentum-preserving scattering rate. In
      this way, we obtain a unified mechanism-without umklapp-for [Formula: see text]
      in a Fermi liquid and the crossover to [Formula: see text] in quantum critical
      regimes. This behavior is widely observed in transition metal oxides, organic
      metals, pnictides, and heavy fermion compounds and has presented a long-standing
      challenge to transport theory. Our hydrodynamic bound allows phonon contributions
      to diffusion constants, including thermal diffusion, to directly affect the
      electrical resistivity.

PMID- 29073055
TI  - The topography of the environment alters the optimal search strategy for active
      particles.
AB  - In environments with scarce resources, adopting the right search strategy can
      make the difference between succeeding and failing, even between life and death.
      At different scales, this applies to molecular encounters in the cell cytoplasm,
      to animals looking for food or mates in natural landscapes, to rescuers during
      search and rescue operations in disaster zones, and to genetic computer
      algorithms exploring parameter spaces. When looking for sparse targets in a
      homogeneous environment, a combination of ballistic and diffusive steps is
      considered optimal; in particular, more ballistic Levy flights with exponent
      [Formula: see text] are generally believed to optimize the search process.
      However, most search spaces present complex topographies. What is the best search
      strategy in these more realistic scenarios? Here, we show that the topography of
      the environment significantly alters the optimal search strategy toward less
      ballistic and more Brownian strategies. We consider an active particle performing
      a blind cruise search for nonregenerating sparse targets in a 2D space with steps
      drawn from a Levy distribution with the exponent varying from [Formula: see text]
      to [Formula: see text] (Brownian). We show that, when boundaries, barriers, and
      obstacles are present, the optimal search strategy depends on the topography of
      the environment, with [Formula: see text] assuming intermediate values in the
      whole range under consideration. We interpret these findings using simple scaling
      arguments and discuss their robustness to varying searcher's size. Our results
      are relevant for search problems at different length scales from animal and human
      foraging to microswimmers' taxis to biochemical rates of reaction.

PMID- 29073057
TI  - Universal photonic quantum computation via time-delayed feedback.
AB  - We propose and analyze a deterministic protocol to generate two-dimensional
      photonic cluster states using a single quantum emitter via time-delayed quantum
      feedback. As a physical implementation, we consider a single atom or atom-like
      system coupled to a 1D waveguide with a distant mirror, where guided photons
      represent the qubits, while the mirror allows the implementation of feedback. We
      identify the class of many-body quantum states that can be produced using this
      approach and characterize them in terms of 2D tensor network states.

PMID- 29073056
TI  - Configurational entropy measurements in extremely supercooled liquids that break
      the glass ceiling.
AB  - Liquids relax extremely slowly on approaching the glass state. One explanation is
      that an entropy crisis, because of the rarefaction of available states, makes it
      increasingly arduous to reach equilibrium in that regime. Validating this
      scenario is challenging, because experiments offer limited resolution, while
      numerical studies lag more than eight orders of magnitude behind experimentally
      relevant timescales. In this work, we not only close the colossal gap between
      experiments and simulations but manage to create in silico configurations that
      have no experimental analog yet. Deploying a range of computational tools, we
      obtain four estimates of their configurational entropy. These measurements
      consistently confirm that the steep entropy decrease observed in experiments is
      also found in simulations, even beyond the experimental glass transition. Our
      numerical results thus extend the observational window into the physics of
      glasses and reinforce the relevance of an entropy crisis for understanding their
      formation.

PMID- 29073058
TI  - Big data modeling to predict platelet usage and minimize wastage in a tertiary
      care system.
AB  - Maintaining a robust blood product supply is an essential requirement to
      guarantee optimal patient care in modern health care systems. However, daily
      blood product use is difficult to anticipate. Platelet products are the most
      variable in daily usage, have short shelf lives, and are also the most expensive
      to produce, test, and store. Due to the combination of absolute need, uncertain
      daily demand, and short shelf life, platelet products are frequently wasted due
      to expiration. Our aim is to build and validate a statistical model to forecast
      future platelet demand and thereby reduce wastage. We have investigated platelet
      usage patterns at our institution, and specifically interrogated the relationship
      between platelet usage and aggregated hospital-wide patient data over a recent
      consecutive 29-mo period. Using a convex statistical formulation, we have found
      that platelet usage is highly dependent on weekday/weekend pattern, number of
      patients with various abnormal complete blood count measurements, and location
      specific hospital census data. We incorporated these relationships in a
      mathematical model to guide collection and ordering strategy. This model
      minimizes waste due to expiration while avoiding shortages; the number of
      remaining platelet units at the end of any day stays above 10 in our model during
      the same period. Compared with historical expiration rates during the same
      period, our model reduces the expiration rate from 10.5 to 3.2%. Extrapolating
      our results to the ~2 million units of platelets transfused annually within the
      United States, if implemented successfully, our model can potentially save ~80
      million dollars in health care costs.

PMID- 29073059
TI  - Rethinking people's conceptions of mental life.
AB  - How do people make sense of the emotions, sensations, and cognitive abilities
      that make up mental life? Pioneering work on the dimensions of mind perception
      has been interpreted as evidence that people consider mental life to have two
      core components-experience (e.g., hunger, joy) and agency (e.g., planning, self
      control) [Gray HM, et al. (2007) Science 315:619]. We argue that this conclusion
      is premature: The experience-agency framework may capture people's understanding
      of the differences among different beings (e.g., dogs, humans, robots, God) but
      not how people parse mental life itself. Inspired by Gray et al.'s bottom-up
      approach, we conducted four large-scale studies designed to assess people's
      conceptions of mental life more directly. This led to the discovery of an
      organization that differs strikingly from the experience-agency framework:
      Instead of a broad distinction between experience and agency, our studies
      consistently revealed three fundamental components of mental life-suites of
      capacities related to the body, the heart, and the mind-with each component
      encompassing related aspects of both experience and agency. This body-heart-mind
      framework distinguishes itself from Gray et al.'s experience-agency framework by
      its clear and importantly different implications for dehumanization, moral
      reasoning, and other important social phenomena.

PMID- 29073060
TI  - How truth wins in opinion dynamics along issue sequences.
AB  - How truth wins in social groups is an important open problem. Classic experiments
      on social groups dealing with truth statement issues present mixed findings on
      the conditions of truth abandonment and reaching a consensus on the truth. No
      theory has been developed and evaluated that might integrate these findings with
      a mathematical model of the interpersonal influence system that alters some or
      all of its members' positions on an issue. In this paper we provide evidence that
      a general model in the network science on opinion dynamics substantially
      clarifies how truth wins in groups.

PMID- 29073061
TI  - Engineering sulfur storage in maize seed proteins without apparent yield loss.
AB  - Sulfur assimilation may limit the pool of methionine and cysteine available for
      incorporation into zeins, the major seed storage proteins in maize. This
      hypothesis was tested by producing transgenic maize with deregulated sulfate
      reduction capacity achieved through leaf-specific expression of the Escherichia
      coli enzyme 3'-phosphoadenosine-5'-phosphosulfate reductase (EcPAPR) that
      resulted in higher methionine accumulation in seeds. The transgenic kernels have
      higher expression of the methionine-rich 10-kDa delta-zein and total protein
      sulfur without reduction of other zeins. This overall increase in the expression
      of the S-rich zeins describes a facet of regulation of these proteins under
      enhanced sulfur assimilation. Transgenic line PE5 accumulates 57.6% more kernel
      methionine than the high-methionine inbred line B101. In feeding trials with
      chicks, PE5 maize promotes significant weight gain compared with nontransgenic
      kernels. Therefore, increased source strength can improve the nutritional value
      of maize without apparent yield loss and may significantly reduce the cost of
      feed supplementation.

PMID- 29073063
TI  - PrimPol is required for replication reinitiation after mtDNA damage.
AB  - Eukaryotic PrimPol is a recently discovered DNA-dependent DNA primase and
      translesion synthesis DNA polymerase found in the nucleus and mitochondria.
      Although PrimPol has been shown to be required for repriming of stalled
      replication forks in the nucleus, its role in mitochondria has remained
      unresolved. Here we demonstrate in vivo and in vitro that PrimPol can reinitiate
      stalled mtDNA replication and can prime mtDNA replication from nonconventional
      origins. Our results not only help in the understanding of how mitochondria cope
      with replicative stress but can also explain some controversial features of the
      lagging-strand replication.

PMID- 29073062
TI  - Small-molecule inhibitors directly target CARD9 and mimic its protective variant
      in inflammatory bowel disease.
AB  - Advances in human genetics have dramatically expanded our understanding of
      complex heritable diseases. Genome-wide association studies have identified an
      allelic series of CARD9 variants associated with increased risk of or protection
      from inflammatory bowel disease (IBD). The predisposing variant of CARD9 is
      associated with increased NF-kappaB-mediated cytokine production. Conversely, the
      protective variant lacks a functional C-terminal domain and is unable to recruit
      the E3 ubiquitin ligase TRIM62. Here, we used biochemical insights into CARD9
      variant proteins to create a blueprint for IBD therapeutics and recapitulated the
      mechanism of the CARD9 protective variant using small molecules. We developed a
      multiplexed bead-based technology to screen compounds for disruption of the CARD9
      TRIM62 interaction. We identified compounds that directly and selectively bind
      CARD9, disrupt TRIM62 recruitment, inhibit TRIM62-mediated ubiquitinylation of
      CARD9, and demonstrate cellular activity and selectivity in CARD9-dependent
      pathways. Taken together, small molecules targeting CARD9 illustrate a path
      toward improved IBD therapeutics.

PMID- 29073064
TI  - Human SHMT inhibitors reveal defective glycine import as a targetable metabolic
      vulnerability of diffuse large B-cell lymphoma.
AB  - The enzyme serine hydroxymethyltransferse (SHMT) converts serine into glycine and
      a tetrahydrofolate-bound one-carbon unit. Folate one-carbon units support purine
      and thymidine synthesis, and thus cell growth. Mammals have both cytosolic SHMT1
      and mitochondrial SHMT2, with the mitochondrial isozyme strongly up-regulated in
      cancer. Here we show genetically that dual SHMT1/2 knockout blocks HCT-116 colon
      cancer tumor xenograft formation. Building from a pyrazolopyran scaffold that
      inhibits plant SHMT, we identify small-molecule dual inhibitors of human SHMT1/2
      (biochemical IC50 ~ 10 nM). Metabolomics and isotope tracer studies demonstrate
      effective cellular target engagement. A cancer cell-line screen revealed that B
      cell lines are particularly sensitive to SHMT inhibition. The one-carbon donor
      formate generally rescues cells from SHMT inhibition, but paradoxically increases
      the inhibitor's cytotoxicity in diffuse large B-cell lymphoma (DLBCL). We show
      that this effect is rooted in defective glycine uptake in DLBCL cell lines,
      rendering them uniquely dependent upon SHMT enzymatic activity to meet glycine
      demand. Thus, defective glycine import is a targetable metabolic deficiency of
      DLBCL.

PMID- 29073065
TI  - Pressure effects on collective density fluctuations in water and protein
      solutions.
AB  - Neutron Brillouin scattering and molecular dynamics simulations have been used to
      investigate protein hydration water density fluctuations as a function of
      pressure. Our results show significant differences between the pressure and
      density dependence of collective dynamics in bulk water and in concentrated
      protein solutions. Pressure-induced changes in the tetrahedral order of the water
      HB network have direct consequences for the high-frequency sound velocity and
      damping coefficients, which we find to be a sensitive probe for changes in the HB
      network structure as well as the wetting of biomolecular surfaces.

PMID- 29073066
TI  - Molecular basis for unique specificity of human TRAF4 for platelets GPIbbeta and
      GPVI.
AB  - Tumor necrosis factor (TNF)-receptor associated factor 4 (TRAF4), an adaptor
      protein with E3-ligase activity, is involved in embryogenesis, cancer initiation
      and progression, and platelet receptor (GPIb-IX-V complex and GPVI)-mediated
      signaling for reactive oxygen species (ROS) production that initiates thrombosis
      at arterial shears. Disruption of platelet receptors and the TRAF4 interaction is
      a potential target for therapeutic intervention by antithrombotic drugs. Here, we
      report a crystal structure of TRAF4 (amino acid residues 290~470) in complex with
      a peptide from the GPIbbeta receptor (amino acid residues 177~181). The GPIbbeta
      peptide binds to a unique shallow surface composed of two hydrophobic pockets on
      TRAF4. Further studies revealed the TRAF4-binding motif Arg-Leu-X-Ala. The TRAF4
      binding motif was present not only in platelet receptors but also in the TGF-beta
      receptor. The current structure will provide a template for furthering our
      understanding of the receptor-binding specificity of TRAF4, TRAF4-mediated
      signaling, and related diseases.

PMID- 29073067
TI  - Self-association of a highly charged arginine-rich cell-penetrating peptide.
AB  - Small-angle X-ray scattering (SAXS) measurements reveal a striking difference in
      intermolecular interactions between two short highly charged peptides-deca
      arginine (R10) and deca-lysine (K10). Comparison of SAXS curves at high and low
      salt concentration shows that R10 self-associates, while interactions between K10
      chains are purely repulsive. The self-association of R10 is stronger at lower
      ionic strengths, indicating that the attraction between R10 molecules has an
      important electrostatic component. SAXS data are complemented by NMR measurements
      and potentials of mean force between the peptides, calculated by means of
      umbrella-sampling molecular dynamics (MD) simulations. All-atom MD simulations
      elucidate the origin of the R10-R10 attraction by providing structural
      information on the dimeric state. The last two C-terminal residues of R10
      constitute an adhesive patch formed by stacking of the side chains of two
      arginine residues and by salt bridges formed between the like-charge ion pair and
      the C-terminal carboxyl groups. A statistical analysis of the Protein Data Bank
      reveals that this mode of interaction is a common feature in proteins.

PMID- 29073068
TI  - Evidence of evolutionary selection for cotranslational folding.
AB  - Recent experiments and simulations have demonstrated that proteins can fold on
      the ribosome. However, the extent and generality of fitness effects resulting
      from cotranslational folding remain open questions. Here we report a genome-wide
      analysis that uncovers evidence of evolutionary selection for cotranslational
      folding. We describe a robust statistical approach to identify loci within genes
      that are both significantly enriched in slowly translated codons and
      evolutionarily conserved. Surprisingly, we find that domain boundaries can
      explain only a small fraction of these conserved loci. Instead, we propose that
      regions enriched in slowly translated codons are associated with cotranslational
      folding intermediates, which may be smaller than a single domain. We show that
      the intermediates predicted by a native-centric model of cotranslational folding
      account for the majority of these loci across more than 500 Escherichia coli
      proteins. By making a direct connection to protein folding, this analysis
      provides strong evidence that many synonymous substitutions have been selected to
      optimize translation rates at specific locations within genes. More generally,
      our results indicate that kinetics, and not just thermodynamics, can
      significantly alter the efficiency of self-assembly in a biological context.

PMID- 29073071
TI  - Phylogenetic diversity anomaly in angiosperms between eastern Asia and eastern
      North America.
AB  - Although eastern Asia (EAS) and eastern North America (ENA) have similar
      climates, plant species richness in EAS greatly exceeds that in ENA. The degree
      to which this diversity difference reflects the ages of the floras or their rates
      of evolutionary diversification has not been quantified. Measures of species
      diversity that do not incorporate the ages of lineages disregard the evolutionary
      distinctiveness of species. In contrast, phylogenetic diversity integrates both
      the number of species and their history of evolutionary diversification. Here we
      compared species diversity and phylogenetic diversity in a large number of
      flowering plant (angiosperm) floras distributed across EAS and ENA, two regions
      with similar contemporary environments and broadly shared floristic history.
      After accounting for climate and sample area, we found both species diversity and
      phylogenetic diversity to be significantly higher in EAS than in ENA. When we
      controlled the number of species statistically, we found that phylogenetic
      diversity remained substantially higher in EAS than in ENA, although it tended to
      converge at high latitude. This pattern held independently for herbs, shrubs, and
      trees. The anomaly in species and phylogenetic diversity likely resulted from
      differences in regional processes, related in part to high climatic and
      topographic heterogeneity, and a strong monsoon climate, in EAS. The broad
      connection between tropical and temperate floras in southern Asia also might have
      played a role in creating the phylogenetic diversity anomaly.

PMID- 29073069
TI  - Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute
      to the Warburg effect.
AB  - Aberrant alternative splicing and epigenetic changes are both associated with
      various cancers, but epigenetic regulation of alternative splicing in cancer is
      largely unknown. Here we report that the intragenic DNA methylation-mediated
      binding of Brother of Regulator of Imprinted Sites (BORIS) at the alternative
      exon of Pyruvate Kinase (PKM) is associated with cancer-specific splicing that
      promotes the Warburg effect and breast cancer progression. Interestingly, the
      inhibition of DNA methylation, BORIS depletion, or CRISPR/Cas9-mediated deletion
      of the BORIS binding site leads to a splicing switch from cancer-specific PKM2 to
      normal PKM1 isoform. This results in the reversal of the Warburg effect and the
      inhibition of breast cancer cell growth, which may serve as a useful approach to
      inhibit the growth of breast cancer cells. Importantly, our results show that in
      addition to PKM splicing, BORIS also regulates the alternative splicing of
      several genes in a DNA methylation-dependent manner. Our findings highlight the
      role of intragenic DNA methylation and DNA binding protein BORIS in cancer
      specific splicing and its role in tumorigenesis.

PMID- 29073072
TI  - Competitive network determines the direction of the diversity-function
      relationship.
AB  - The structure of the competitive network is an important driver of biodiversity
      and coexistence in natural communities. In addition to determining which species
      survive, the nature and intensity of competitive interactions within the network
      also affect the growth, productivity, and abundances of those individuals that
      persist. As such, the competitive network structure may likewise play an
      important role in determining community-level functioning by capturing the net
      costs of competition. Here, using an experimental system comprising 18 wood decay
      basidiomycete fungi, we test this possibility by quantifying the links among
      competitive network structure, species diversity, and community function. We show
      that species diversity alone has negligible impacts on community functioning, but
      that diversity interacts with two key properties of the competitive network
      competitive intransitivity and average competitive ability-to ultimately shape
      biomass production, respiration, and carbon use efficiency. Most notably, highly
      intransitive communities comprising weak competitors exhibited a positive
      diversity-function relationship, whereas weakly intransitive communities
      comprising strong competitors exhibited a negative relationship. These findings
      demonstrate that competitive network structure can be an important determinant of
      community-level functioning, capturing a gradient from weakly to strongly
      competitive communities. Our research suggests that the competitive network may
      therefore act as a unifying link between diversity and function, providing key
      insight as to how and when losses in biodiversity will impact ecosystem function.

PMID- 29073070
TI  - Diel cycling and long-term persistence of viruses in the ocean's euphotic zone.
AB  - Viruses are fundamental components of marine microbial communities that
      significantly influence oceanic productivity, biogeochemistry, and ecosystem
      processes. Despite their importance, the temporal activities and dynamics of
      viral assemblages in natural settings remain largely unexplored. Here we report
      the transcriptional activities and variability of dominant dsDNA viruses in the
      open ocean's euphotic zone over daily and seasonal timescales. While dsDNA
      viruses exhibited some fluctuation in abundance in both cellular and viral size
      fractions, the viral assemblage was remarkably stable, with the most abundant
      viral types persisting over many days. More extended time series indicated that
      long-term persistence (>1 y) was the rule for most dsDNA viruses observed,
      suggesting that both core viral genomes as well as viral community structure were
      conserved over interannual periods. Viral gene transcription in host cell
      assemblages revealed diel cycling among many different viral types. Most notably,
      an afternoon peak in cyanophage transcriptional activity coincided with a peak in
      Prochlorococcus DNA replication, indicating coordinated diurnal coupling of virus
      and host reproduction. In aggregate, our analyses suggested a tightly
      synchronized diel coupling of viral and cellular replication cycles in both
      photoautotrophic and heterotrophic bacterial hosts. A surprising consequence of
      these findings is that diel cycles in the ocean's photic zone appear to be
      universal organizing principles that shape ecosystem dynamics, ecological
      interactions, and biogeochemical cycling of both cellular and acellular community
      components.

PMID- 29073073
TI  - Insight into the growth pattern and bone fusion of basal birds from an Early
      Cretaceous enantiornithine bird.
AB  - Bird skeletons exhibit remarkable modifications that allow for flight. The most
      distinguishable features are the fusion of the bones in the hand, feet, and
      pelvis into composite rigid and bony structures. However, the historical origins
      of these avian bone fusions remain elusive because of the rarity of transitional
      fossils and developmental studies on modern birds. Here, we describe an Early
      Cretaceous bird (120 Mya) that has fully fused alular-major metacarpals and
      pelvis. We discuss the manus and pelvis fusions across Paravian phylogeny and
      demonstrate that these features evolved independently across nonavian theropods,
      Enantiornithes, and Ornithuromorpha. The fusions of these bones are rare in known
      nonavian theropods and Early Cretaceous birds but are well established among Late
      Cretaceous and modern birds, revealing a complicated evolution pattern
      unrecognized previously. We posit that the developments of bone fusion were
      polymorphic close to the origin of birds, resulting in the varying degrees of
      fusion in Paraves. However, that development polymorphism appears to be
      fundamentally restricted along the line to modern birds by the Late Cretaceous,
      where all birds have a completely fused manus and pelvis. Such changes likely
      correspond to a refinement of flight capability. Alternatively, the degree of
      bone fusion in this primitive bird may have been related to modifications in
      genes or developmental paths. Future studies and fossil discoveries are required
      to clarify these hypotheses and pinpoint the developmental pathways involving the
      bone fusions in early avian evolution through to their modern pattern.

PMID- 29073075
TI  - Selective neutralization of IL-12 p40 monomer induces death in prostate cancer
      cells via IL-12-IFN-gamma.
AB  - Cancer cells are adept at evading cell death, but the underlying mechanisms are
      poorly understood. IL-12 plays a critical role in the early inflammatory response
      to infection and in the generation of T-helper type 1 cells, favoring cell
      mediated immunity. IL-12 is composed of two different subunits, p40 and p35. This
      study underlines the importance of IL-12 p40 monomer (p40) in helping cancer
      cells to escape cell death. We found that different mouse and human cancer cells
      produced greater levels of p40 than p40 homodimer (p402), IL-12, or IL-23.
      Similarly, the serum level of p40 was much greater in patients with prostate
      cancer than in healthy control subjects. Selective neutralization of p40, but not
      p402, by mAb stimulated death in different cancer cells in vitro and in vivo in a
      tumor model. Interestingly, p40 was involved in the arrest of IL-12 receptor (IL
      12R) IL-12Rbeta1, but not IL-12Rbeta2, in the membrane, and that p40
      neutralization induced the internalization of IL-12Rbeta1 via caveolin and caused
      cancer cell death via the IL-12-IFN-gamma pathway. These studies identify a role
      of p40 monomer in helping cancer cells to escape cell death via suppression of IL
      12Rbeta1 internalization.

PMID- 29073074
TI  - FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral
      disc disease in dogs.
AB  - Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and
      premature degeneration and calcification of intervertebral discs. Independent
      genome-wide association analyses for skeletal dysplasia (short limbs) within a
      single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across
      breeds (PBonferroni = 4.0 * 10-10) both identified a significant association to
      the same region on CFA12. Whole genome sequencing identified a highly expressed
      FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb
      length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone
      length in dogs is a unique example of multiple disease-causing retrocopies of the
      same parental gene in a mammalian species. FGF signaling abnormalities have been
      associated with skeletal dysplasia in humans, and our findings present
      opportunities for both selective elimination of a medically and financially
      devastating disease in dogs and further understanding of the ever-growing
      complexity of retrogene biology.

PMID- 29073076
TI  - Macrophage-like nanoparticles concurrently absorbing endotoxins and
      proinflammatory cytokines for sepsis management.
AB  - Sepsis, resulting from uncontrolled inflammatory responses to bacterial
      infections, continues to cause high morbidity and mortality worldwide. Currently,
      effective sepsis treatments are lacking in the clinic, and care remains primarily
      supportive. Here we report the development of macrophage biomimetic nanoparticles
      for the management of sepsis. The nanoparticles, made by wrapping polymeric cores
      with cell membrane derived from macrophages, possess an antigenic exterior the
      same as the source cells. By acting as macrophage decoys, these nanoparticles
      bind and neutralize endotoxins that would otherwise trigger immune activation. In
      addition, these macrophage-like nanoparticles sequester proinflammatory cytokines
      and inhibit their ability to potentiate the sepsis cascade. In a mouse
      Escherichia coli bacteremia model, treatment with macrophage mimicking
      nanoparticles, termed MPhi-NPs, reduced proinflammatory cytokine levels,
      inhibited bacterial dissemination, and ultimately conferred a significant
      survival advantage to infected mice. Employing MPhi-NPs as a biomimetic
      detoxification strategy shows promise for improving patient outcomes, potentially
      shifting the current paradigm of sepsis management.

PMID- 29073077
TI  - Breast tumor cell-specific knockout of Twist1 inhibits cancer cell plasticity,
      dissemination, and lung metastasis in mice.
AB  - Twist1 is an epithelial-mesenchymal transition (EMT)-inducing transcription
      factor (TF) that promotes cell migration and invasion. To determine the intrinsic
      role of Twist1 in EMT and breast cancer initiation, growth, and metastasis, we
      developed mouse models with an oncogene-induced mammary tumor containing wild
      type (WT) Twist1 or tumor cell-specific Twist1 knockout (Twist1TKO). Twist1
      knockout showed no effects on tumor initiation and growth. In both models with
      early-stage tumor cells, Twist1, and mesenchymal markers were not expressed, and
      lung metastasis was absent. Twist1 expression was detected in ~6% of the advanced
      WT tumor cells. Most of these Twist1+ cells coexpressed several other EMT
      inducing TFs (Snail, Slug, Zeb2), lost ERalpha and luminal marker K8, acquired
      basal cell markers (K5, p63), and exhibited a partial EMT plasticity (E
      cadherin+/vimentin+). In advanced Twist1TKO tumor cells, Twist1 knockout largely
      diminished the expression of the aforementioned EMT-inducing TFs and basal and
      mesenchymal markers, but maintained the expression of the luminal markers.
      Circulating tumor cells (CTCs) were commonly detected in mice with advanced WT
      tumors, but not in mice with advanced Twist1TKO tumors. Nearly all WT CTCs
      coexpressed Twist1 with other EMT-inducing TFs and both epithelial and
      mesenchymal markers. Mice with advanced WT tumors developed extensive lung
      metastasis consisting of luminal tumor cells with silenced Twist1 and mesenchymal
      marker expression. Mice with advanced Twist1TKO tumors developed very little lung
      metastasis. Therefore, Twist1 is required for the expression of other EMT
      inducing TFs in a small subset of tumor cells. Together, they induce partial EMT,
      basal-like tumor progression, intravasation, and metastasis.

PMID- 29073078
TI  - Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner.
AB  - WT p53 is critical for tumor suppression, whereas mutant p53 promotes tumor
      progression. Nerve injury-induced protein 1 (Ninj1) is a target of p53 and forms
      a feedback loop with p53 by repressing p53 mRNA translation. Here, we show that
      loss of Ninj1 increased mutant p53 expression and, subsequently, enhanced cell
      growth and migration in cells carrying a mutant p53. In contrast, loss of Ninj1
      inhibited cell growth and migration in cells carrying a WT p53. To explore the
      biological significance of Ninj1, we generated a cohort of Ninj1-deficient mice
      and found that Ninj1+/- mice were prone to systemic inflammation and insulitis,
      but not to spontaneous tumors. We also found that loss of Ninj1 altered the tumor
      susceptibility in both mutant p53 and p53-null background. Specifically, in a
      mutant p53(R270H) background, Ninj1 deficiency shortened the lifespan, altered
      the tumor spectrum, and increased tumor burden, likely via enhanced expression of
      mutant p53. In a p53-null background, Ninj1 deficiency significantly increased
      the incidence of T-lymphoblastic lymphoma. Taken together, our data suggest that
      depending on p53 genetic status, Ninj1 has two opposing functions in
      tumorigenesis and that the Ninj1-p53 loop may be targeted to manage inflammatory
      diseases and cancer.

PMID- 29073079
TI  - Inhibition of DAI-dependent necroptosis by the Z-DNA binding domain of the
      vaccinia virus innate immune evasion protein, E3.
AB  - Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which
      contains an N-terminal Z-nucleic acid binding (Zalpha) domain that is critical
      for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is
      necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the
      Zalpha domain of E3 (VACV-E3LDelta83N) induced rapid RIPK3-dependent cell death
      in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor,
      GSK872, and infection with this mutant virus led to phosphorylation and
      aggregation of MLKL, the executioner of necroptosis. In 293T cells, induction of
      necroptosis depended on expression of RIPK3 as well as the host-encoded Zalpha
      domain-containing DNA sensor, DAI. VACV-E3LDelta83N is attenuated in vivo, and
      pathogenicity was restored in either RIPK3- or DAI-deficient mice. These data
      demonstrate that the N terminus of the VACV E3 protein prevents DAI-mediated
      induction of necroptosis.

PMID- 29073080
TI  - Maladaptive DNA repair is the ultimate contributor to the death of trimethoprim
      treated cells under aerobic and anaerobic conditions.
AB  - The bactericidal effects of antibiotics are undoubtedly triggered by target
      specific interactions, but there is growing evidence that an important aspect of
      cytotoxicity results from treatment-induced metabolic perturbations. In this
      study, we characterized molecular mechanisms whereby trimethoprim treatment
      results in cell death, using Escherichia coli as the model organism. E. coli
      cells grown in rich medium that contained all amino acids and low amounts of
      thymidine were treated with trimethoprim under aerobic and anaerobic conditions.
      Under these growth conditions, accelerated thymine depletion is the primary
      trigger of the processes leading to cell death. Thymine depletion-induced DNA
      replication stress leads to the production of reactive oxygen species under
      aerobic conditions and of the DNA-damaging byproducts of nitrate respiration
      under anaerobic conditions. Lowering the DNA replication initiation rate by
      introducing the dnaA(Sx) allele or by overexpressing Hda protein reduces the
      number of active replication forks, which reduces the consumption of thymidine
      and increases resistance to trimethoprim under both aerobic and anaerobic
      conditions. Analysis of the involvement of DNA repair enzymes in trimethoprim
      induced cytotoxicity clearly indicates that different amounts and/or different
      types of DNA lesions are produced in the presence or absence of oxygen.
      Maladaptive processing of the DNA damage by DNA repair enzymes, in particular by
      MutM and MutY DNA glycosylases, ultimately contributes to cell death.

PMID- 29073082
TI  - Transcription factor ISX mediates the cross talk between diet and immunity.
AB  - The intestinal epithelium is a major site for the conversion of dietary beta
      carotene to retinaldehyde by the enzyme BCO1. The majority of retinaldehyde is
      further metabolized to retinol (vitamin A), esterified and packaged into
      triacylglycerol-rich chylomicrons for bodily distribution. Some serve on-site for
      the synthesis of retinoic acid, a hormone-like compound, which exerts pleiotropic
      and dominant effects on gastrointestinal immunity. We report here that the
      intestine-specific homeobox protein ISX is critical to control the metabolic flow
      of beta-carotene through this important branching point of vitamin A metabolism.
      This transcription factor represses Bco1 gene expression in response to retinoic
      acid signaling. In ISX-deficient mice, uncontrolled Bco1 gene expression led to
      increased retinoid production in the intestine. Systemically, this production
      resulted in highly elevated hepatic retinoid stores. In the intestine, it
      increased the expression of retinoic acid-inducible target genes such as Aldh1a2,
      Dhrs3, and Ccr9 The beta-carotene-inducible disruption of retinoid homeostasis
      affected gut-homing and differentiation of lymphocytes and displayed
      morphologically in large lymphoid follicles along the intestine. Furthermore, it
      was associated with an infiltration of the pancreas by gut-derived lymphocytes
      that manifested as a pancreatic insulitis with beta-islet cell destruction and
      systemic glucose intolerance. Thus, our study identifies an important molecular
      interlink between diet and immunity and indicates that vitamin A homeostasis must
      be tightly controlled by ISX to maintain immunity and tolerance at the intestinal
      barrier.

PMID- 29073081
TI  - TREM2 deficiency attenuates neuroinflammation and protects against
      neurodegeneration in a mouse model of tauopathy.
AB  - Variants in the gene encoding the triggering receptor expressed on myeloid cells
      2 (TREM2) were recently found to increase the risk for developing Alzheimer's
      disease (AD). In the brain, TREM2 is predominately expressed on microglia, and
      its association with AD adds to increasing evidence implicating a role for the
      innate immune system in AD initiation and progression. Thus far, studies have
      found TREM2 is protective in the response to amyloid pathology while variants
      leading to a loss of TREM2 function impair microglial signaling and are
      deleterious. However, the potential role of TREM2 in the context of tau pathology
      has not yet been characterized. In this study, we crossed Trem2+/+ (T2+/+) and
      Trem2-/- (T2-/-) mice to the PS19 human tau transgenic line (PS) to investigate
      whether loss of TREM2 function affected tau pathology, the microglial response to
      tau pathology, or neurodegeneration. Strikingly, by 9 mo of age, T2-/-PS mice
      exhibited significantly less brain atrophy as quantified by ventricular
      enlargement and preserved cortical volume in the entorhinal and piriform regions
      compared with T2+/+PS mice. However, no TREM2-dependent differences were observed
      for phosphorylated tau staining or insoluble tau levels. Rather, T2-/-PS mice
      exhibited significantly reduced microgliosis in the hippocampus and piriform
      cortex compared with T2+/+PS mice. Gene expression analyses and immunostaining
      revealed microglial activation was significantly attenuated in T2-/-PS mice, and
      there were lower levels of inflammatory cytokines and astrogliosis. These
      unexpected findings suggest that impairing microglial TREM2 signaling reduces
      neuroinflammation and is protective against neurodegeneration in the setting of
      pure tauopathy.

PMID- 29073083
TI  - Natural variation identifies genes affecting drought-induced abscisic acid
      accumulation in Arabidopsis thaliana.
AB  - Accumulation of the stress hormone abscisic acid (ABA) in response to drought and
      low water-potential controls many downstream acclimation mechanisms. However,
      mechanisms controlling ABA accumulation itself are less known. There was a 10
      fold range of variation in ABA levels among nearly 300 Arabidopsis thaliana
      accessions exposed to the same low water-potential severity. Genome-wide
      association analysis (GWAS) identified genomic regions containing clusters of ABA
      associated SNPs. Candidate genes within these regions included few genes with
      known stress or ABA-related function. The GWAS data were used to guide reverse
      genetic analysis, which found effectors of ABA accumulation. These included
      plasma-membrane-localized signaling proteins such as receptor-like kinases,
      aspartic protease, a putative lipid-binding START domain protein, and other
      membrane proteins of unknown function as well as a RING U-box protein and
      possible effect of tonoplast transport on ABA accumulation. Putative loss-of
      function polymorphisms within the START domain protein were associated with
      climate factors at accession sites of origin, indicating its potential
      involvement in drought adaptation. Overall, using ABA accumulation as a basis for
      a combined GWAS-reverse genetic strategy revealed the broad natural variation in
      low-water-potential-induced ABA accumulation and was successful in identifying
      genes that affect ABA levels and may act in upstream drought-related sensing and
      signaling mechanisms. ABA effector loci were identified even when each one was of
      incremental effect, consistent with control of ABA accumulation being distributed
      among the many branches of ABA metabolism or mediated by genes with partially
      redundant function.

PMID- 29073084
TI  - Disruption and rescue of interareal theta phase coupling and adaptive behavior.
AB  - Rescuing executive functions in people with neurological and neuropsychiatric
      disorders has been a major goal of psychology and neuroscience for decades.
      Innovative computer-training regimes for executive functions have made tremendous
      inroads, yet the positive effects of training have not always translated into
      improved cognitive functioning and often take many days to emerge. In the present
      study, we asked whether it was possible to immediately change components of
      executive function by directly manipulating neural activity using a stimulation
      technology called high-definition transcranial alternating current stimulation
      (HD-tACS). Twenty minutes of inphase stimulation over medial frontal cortex (MFC)
      and right lateral prefrontal cortex (lPFC) synchronized theta (~6 Hz) rhythms
      between these regions in a frequency and spatially specific manner and rapidly
      improved adaptive behavior with effects lasting longer than 40 min. In contrast,
      antiphase stimulation in the same individuals desynchronized MFC-lPFC theta phase
      coupling and impaired adaptive behavior. Surprisingly, the exogenously driven
      impairments in performance could be instantly rescued by reversing the phase
      angle of alternating current. The results suggest executive functions can be
      rapidly up- or down-regulated by modulating theta phase coupling of distant
      frontal cortical areas and can contribute to the development of tools for
      potentially normalizing executive dysfunction in patient populations.

PMID- 29073086
TI  - Efficient large-scale wind turbine deployment can meet global electricity
      generation needs.

PMID- 29073087
TI  - Reply to Badger and Volker: Correctly estimating wind resources at large scales
      requires more than simple extrapolation.

PMID- 29073085
TI  - Thermosensitivity of growth is determined by chaperone-mediated proteome
      reallocation.
AB  - Maintenance of a properly folded proteome is critical for bacterial survival at
      notably different growth temperatures. Understanding the molecular basis of
      thermoadaptation has progressed in two main directions, the sequence and
      structural basis of protein thermostability and the mechanistic principles of
      protein quality control assisted by chaperones. Yet we do not fully understand
      how structural integrity of the entire proteome is maintained under stress and
      how it affects cellular fitness. To address this challenge, we reconstruct a
      genome-scale protein-folding network for Escherichia coli and formulate a
      computational model, FoldME, that provides statistical descriptions of multiscale
      cellular response consistent with many datasets. FoldME simulations show (i) that
      the chaperones act as a system when they respond to unfolding stress rather than
      achieving efficient folding of any single component of the proteome, (ii) how the
      proteome is globally balanced between chaperones for folding and the complex
      machinery synthesizing the proteins in response to perturbation, (iii) how this
      balancing determines growth rate dependence on temperature and is achieved
      through nonspecific regulation, and (iv) how thermal instability of the
      individual protein affects the overall functional state of the proteome. Overall,
      these results expand our view of cellular regulation, from targeted specific
      control mechanisms to global regulation through a web of nonspecific competing
      interactions that modulate the optimal reallocation of cellular resources. The
      methodology developed in this study enables genome-scale integration of
      environment-dependent protein properties and a proteome-wide study of cellular
      stress responses.

PMID- 29073088
TI  - Simulations predict microbial responses in the environment? This environment
      disagrees retrospectively.

PMID- 29073089
TI  - Reply to Delmont and Eren: Strain variants and population structure during the
      Deepwater Horizon oil spill.

PMID- 29073090
TI  - Black-swan events: Population crashes or temporary emigration?

PMID- 29073091
TI  - Reply to Youngflesh and Lynch: Migration and population growth rate in animal
      black-swan events.

PMID- 29073092
TI  - Unique amalgamation of primary and secondary structural elements transform
      peptaibols into potent bioactive cell-penetrating peptides.
AB  - Mass-spectrometry-based metabolomics and molecular phylogeny data were used to
      identify a metabolically prolific strain of Tolypocladium that was obtained from
      a deep-water Great Lakes sediment sample. An investigation of the isolate's
      secondary metabolome resulted in the purification of a 22-mer peptaibol,
      gichigamin A (1). This peptidic natural product exhibited an amino acid sequence
      including several beta-alanines that occurred in a repeating alphaalphabeta
      motif, causing the compound to adopt a unique right-handed 311 helical structure.
      The unusual secondary structure of 1 was confirmed by spectroscopic approaches
      including solution NMR, electronic circular dichroism (ECD), and single-crystal X
      ray diffraction analyses. Artificial and cell-based membrane permeability assays
      provided evidence that the unusual combination of structural features in
      gichigamins conferred on them an ability to penetrate the outer membranes of
      mammalian cells. Compound 1 exhibited potent in vitro cytotoxicity (GI50 0.55 +/-
      0.04 uM) and in vivo antitumor effects in a MIA PaCa-2 xenograft mouse model.
      While the primary mechanism of cytotoxicity for 1 was consistent with ion
      leakage, we found that it was also able to directly depolarize mitochondria.
      Semisynthetic modification of 1 provided several analogs, including a C-terminus
      linked coumarin derivative (22) that exhibited appreciably increased potency
      (GI50 5.4 +/- 0.1 nM), but lacked ion leakage capabilities associated with a
      majority of naturally occurring peptaibols such as alamethicin. Compound 22 was
      found to enter intact cells and induced cell death in a process that was preceded
      by mitochondrial depolarization.

PMID- 29073093
TI  - Topological phenomena in classical optical networks.
AB  - We propose a scheme to realize a topological insulator with optical-passive
      elements and analyze the effects of Kerr nonlinearities in its topological
      behavior. In the linear regime, our design gives rise to an optical spectrum with
      topological features and where the bandwidths and bandgaps are dramatically
      broadened. The resulting edge modes cover a very wide frequency range. We relate
      this behavior to the fact that the effective Hamiltonian describing the system's
      amplitudes is long range. We also develop a method to analyze the scheme in the
      presence of a Kerr medium. We assess robustness and stability of the topological
      features and predict the presence of chiral squeezed fluctuations at the edges in
      some parameter regimes.

PMID- 29073094
TI  - Mechanistic principles underlying regulation of the actin cytoskeleton by
      phosphoinositides.
AB  - The actin cytoskeleton powers membrane deformation during many cellular
      processes, such as migration, morphogenesis, and endocytosis. Membrane
      phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2],
      regulate the activities of many actin-binding proteins (ABPs), including
      profilin, cofilin, Dia2, N-WASP, ezrin, and moesin, but the underlying molecular
      mechanisms have remained elusive. Moreover, because of a lack of available
      methodology, the dynamics of membrane interactions have not been experimentally
      determined for any ABP. Here, we applied a combination of biochemical assays,
      photobleaching/activation approaches, and atomistic molecular dynamics
      simulations to uncover the molecular principles by which ABPs interact with
      phosphoinositide-rich membranes. We show that, despite using different domains
      for lipid binding, these proteins associate with membranes through similar
      multivalent electrostatic interactions, without specific binding pockets or
      penetration into the lipid bilayer. Strikingly, our experiments reveal that these
      proteins display enormous differences in the dynamics of membrane interactions
      and in the ranges of phosphoinositide densities that they sense. Profilin and
      cofilin display transient, low-affinity interactions with phosphoinositide-rich
      membranes, whereas F-actin assembly factors Dia2 and N-WASP reside on
      phosphoinositide-rich membranes for longer periods to perform their functions.
      Ezrin and moesin, which link the actin cytoskeleton to the plasma membrane, bind
      membranes with very high affinity and slow dissociation dynamics. Unlike
      profilin, cofilin, Dia2, and N-WASP, they do not require high "stimulus
      responsive" phosphoinositide density for membrane binding. Moreover, ezrin can
      limit the lateral diffusion of PI(4,5)P2 along the lipid bilayer. Together, these
      findings demonstrate that membrane-interaction mechanisms of ABPs evolved to
      precisely fulfill their specific functions in cytoskeletal dynamics.

PMID- 29073095
TI  - Broad role for YBX1 in defining the small noncoding RNA composition of exosomes.
AB  - RNA is secreted from cells enclosed within extracellular vesicles (EVs). Defining
      the RNA composition of EVs is challenging due to their coisolation with
      contaminants, lack of knowledge of the mechanisms of RNA sorting into EVs, and
      limitations of conventional RNA-sequencing methods. Here we present our
      observations using thermostable group II intron reverse transcriptase sequencing
      (TGIRT-seq) to characterize the RNA extracted from HEK293T cell EVs isolated by
      flotation gradient ultracentrifugation and from exosomes containing the
      tetraspanin CD63 further purified from the gradient fractions by immunoisolation.
      We found that EV-associated transcripts are dominated by full-length, mature
      transfer RNAs (tRNAs) and other small noncoding RNAs (ncRNAs) encapsulated within
      vesicles. A substantial proportion of the reads mapping to protein-coding genes,
      long ncRNAs, and antisense RNAs were due to DNA contamination on the surface of
      vesicles. Nevertheless, sequences mapping to spliced mRNAs were identified within
      HEK293T cell EVs and exosomes, among the most abundant being transcripts
      containing a 5' terminal oligopyrimidine (5' TOP) motif. Our results indicate
      that the RNA-binding protein YBX1, which is required for the sorting of selected
      miRNAs into exosomes, plays a role in the sorting of highly abundant small ncRNA
      species, including tRNAs, Y RNAs, and Vault RNAs. Finally, we obtained evidence
      for an EV-specific tRNA modification, perhaps indicating a role for
      posttranscriptional modification in the sorting of some RNA species into EVs. Our
      results suggest that EVs and exosomes could play a role in the purging and
      intercellular transfer of excess free RNAs, including full-length tRNAs and other
      small ncRNAs.

PMID- 29073096
TI  - Staufen1 inhibits MyoD translation to actively maintain muscle stem cell
      quiescence.
AB  - Tissue regeneration depends on the timely activation of adult stem cells. In
      skeletal muscle, the adult stem cells maintain a quiescent state and proliferate
      upon injury. We show that muscle stem cells (MuSCs) use direct translational
      repression to maintain the quiescent state. High-resolution single-molecule and
      single-cell analyses demonstrate that quiescent MuSCs express high levels of
      Myogenic Differentiation 1 (MyoD) transcript in vivo, whereas MyoD protein is
      absent. RNA pulldowns and costainings show that MyoD mRNA interacts with
      Staufen1, a potent regulator of mRNA localization, translation, and stability.
      Staufen1 prevents MyoD translation through its interaction with the MyoD 3'-UTR.
      MuSCs from Staufen1 heterozygous (Staufen1+/-) mice have increased MyoD protein
      expression, exit quiescence, and begin proliferating. Conversely, blocking MyoD
      translation maintains the quiescent phenotype. Collectively, our data show that
      MuSCs express MyoD mRNA and actively repress its translation to remain quiescent
      yet primed for activation.

PMID- 29073097
TI  - Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated
      by microRNA-1 in physiologic and pathologic hypertrophy.
AB  - The mitochondrial Ca2+ uniporter complex (MCUC) is a multimeric ion channel
      which, by tuning Ca2+ influx into the mitochondrial matrix, finely regulates
      metabolic energy production. In the heart, this dynamic control of mitochondrial
      Ca2+ uptake is fundamental for cardiomyocytes to adapt to either physiologic or
      pathologic stresses. Mitochondrial calcium uniporter (MCU), which is the core
      channel subunit of MCUC, has been shown to play a critical role in the response
      to beta-adrenoreceptor stimulation occurring during acute exercise. The molecular
      mechanisms underlying the regulation of MCU, in conditions requiring chronic
      increase in energy production, such as physiologic or pathologic cardiac growth,
      remain elusive. Here, we show that microRNA-1 (miR-1), a member of the muscle
      specific microRNA (myomiR) family, is responsible for direct and selective
      targeting of MCU and inhibition of its translation, thereby affecting the
      capacity of the mitochondrial Ca2+ uptake machinery. Consistent with the role of
      miR-1 in heart development and cardiomyocyte hypertrophic remodeling, we
      additionally found that MCU levels are inversely related with the myomiR content,
      in murine and, remarkably, human hearts from both physiologic (i.e., postnatal
      development and exercise) and pathologic (i.e., pressure overload) myocardial
      hypertrophy. Interestingly, the persistent activation of beta-adrenoreceptors is
      likely one of the upstream repressors of miR-1 as treatment with beta-blockers in
      pressure-overloaded mouse hearts prevented its down-regulation and the consequent
      increase in MCU content. Altogether, these findings identify the miR-1/MCU axis
      as a factor in the dynamic adaptation of cardiac cells to hypertrophy.

PMID- 29073098
TI  - Modulation of apoptotic response by LAR family phosphatases-cIAP1 signaling
      during urinary tract morphogenesis.
AB  - The elimination of unwanted cells by apoptosis is necessary for tissue
      morphogenesis. However, the cellular control of morphogenetic apoptosis is poorly
      understood, notably the modulation of cell sensitivity to apoptotic stimuli.
      Ureter maturation, the process by which the ureter is displaced to the bladder
      wall, represents an exquisite example of morphogenetic apoptosis, requiring the
      receptor protein tyrosine phosphatases (RPTPs): LAR and RPTPsigma. Here we show
      that LAR-RPTPs act through cellular inhibitor of apoptosis protein 1 (cIAP1) to
      modulate caspase 3,7-mediated ureter maturation. Pharmacologic or genetic
      inactivation of cIAP1 reverts the apoptotic deficit of LAR-RPTP-deficient
      embryos. Moreover, Birc2 (cIAP1) inactivation generates excessive apoptosis
      leading to vesicoureteral reflux in newborns, which underscores the importance of
      apoptotic modulation during urinary tract morphogenesis. We finally demonstrate
      that LAR-RPTP deficiency increases cIAP1 stability during apoptotic cell death.
      Together these results identify a mode of cIAP1 regulation playing a critical
      role in the cellular response to apoptotic pathway activation in the embryo.

PMID- 29073099
TI  - Mutator genomes decay, despite sustained fitness gains, in a long-term experiment
      with bacteria.
AB  - Understanding the extreme variation among bacterial genomes remains an unsolved
      challenge in evolutionary biology, despite long-standing debate about the
      relative importance of natural selection, mutation, and random drift. A
      potentially important confounding factor is the variation in mutation rates
      between lineages and over evolutionary history, which has been documented in
      several species. Mutation accumulation experiments have shown that
      hypermutability can erode genomes over short timescales. These results, however,
      were obtained under conditions of extremely weak selection, casting doubt on
      their general relevance. Here, we circumvent this limitation by analyzing genomes
      from mutator populations that arose during a long-term experiment with
      Escherichia coli, in which populations have been adaptively evolving for >50,000
      generations. We develop an analytical framework to quantify the relative
      contributions of mutation and selection in shaping genomic characteristics, and
      we validate it using genomes evolved under regimes of high mutation rates with
      weak selection (mutation accumulation experiments) and low mutation rates with
      strong selection (natural isolates). Our results show that, despite sustained
      adaptive evolution in the long-term experiment, the signature of selection is
      much weaker than that of mutational biases in mutator genomes. This finding
      suggests that relatively brief periods of hypermutability can play an outsized
      role in shaping extant bacterial genomes. Overall, these results highlight the
      importance of genomic draft, in which strong linkage limits the ability of
      selection to purge deleterious mutations. These insights are also relevant to
      other biological systems evolving under strong linkage and high mutation rates,
      including viruses and cancer cells.

PMID- 29073100
TI  - Kinship and familiarity mitigate costs of social conflict between Seychelles
      warbler neighbors.
AB  - Because virtually all organisms compete with others in their social environment,
      mechanisms that reduce conflict between interacting individuals are crucial for
      the evolution of stable families, groups, and societies. Here, we tested whether
      costs of social conflict over territorial space between Seychelles warblers
      (Acrocephalus sechellensis) are mitigated by kin-selected (genetic relatedness)
      or mutualistic (social familiarity) mechanisms. By measuring longitudinal changes
      in individuals' body mass and telomere length, we demonstrated that the fitness
      costs of territoriality are driven by a complex interplay between relatedness,
      familiarity, local density, and sex. Physical fights were less common at
      territory boundaries shared between related or familiar males. In line with this,
      male territory owners gained mass when living next to related or familiar males
      and also showed less telomere attrition when living next to male kin.
      Importantly, these relationships were strongest in high-density areas of the
      population. Males also had more rapid telomere attrition when living next to
      unfamiliar male neighbors, but mainly when relatedness to those neighbors was
      also low. In contrast, neither kinship nor familiarity was linked to body mass or
      telomere loss in female territory owners. Our results indicate that resolving
      conflict over territorial space through kin-selected or mutualistic pathways can
      reduce both immediate energetic costs and permanent somatic damage, thus
      providing an important mechanism to explain fine-scale population structure and
      cooperation between different social units across a broad range of taxa.

PMID- 29073101
TI  - UTX-guided neural crest function underlies craniofacial features of Kabuki
      syndrome.
AB  - Kabuki syndrome, a congenital craniofacial disorder, manifests from mutations in
      an X-linked histone H3 lysine 27 demethylase (UTX/KDM6A) or a H3 lysine 4
      methylase (KMT2D). However, the cellular and molecular etiology of histone
      modifying enzymes in craniofacial disorders is unknown. We now establish Kabuki
      syndrome as a neurocristopathy, whereby the majority of clinical features are
      modeled in mice carrying neural crest (NC) deletion of UTX, including
      craniofacial dysmorphism, cardiac defects, and postnatal growth retardation.
      Female UTX NC knockout (FKO) demonstrates enhanced phenotypic severity over males
      (MKOs), due to partial redundancy with UTY, a Y-chromosome demethylase-dead
      homolog. Thus, NC cells may require demethylase-independent UTX activity.
      Consistently, Kabuki causative point mutations upstream of the JmjC domain do not
      disrupt UTX demethylation. We have isolated primary NC cells at a phenocritical
      postmigratory timepoint in both FKO and MKO mice, and genome-wide expression and
      histone profiling have revealed UTX molecular function in establishing
      appropriate chromatin structure to regulate crucial NC stem-cell signaling
      pathways. However, the majority of UTX regulated genes do not experience
      aberrations in H3K27me3 or H3K4me3, implicating alternative roles for UTX in
      transcriptional control. These findings are substantiated through demethylase
      dead knockin mutation of UTX, which supports appropriate facial development.

PMID- 29073102
TI  - Human papillomavirus oncoproteins induce a reorganization of epithelial
      associated gammadelta T cells promoting tumor formation.
AB  - It has been shown that gammadelta T cells protect against the formation of
      squamous cell carcinoma (SCC) in several models. However, the role of gammadelta
      T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third
      leading cause of death by cancer in women, is unknown. Here, we investigated the
      impact of gammadelta T cells in a transgenic mouse model of carcinogenesis
      induced by HPV16 oncoproteins. Surprisingly, gammadelta T cells promoted the
      development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a
      decrease in epidermal Skint1 expression and the associated antitumor Vgamma5+
      gammadelta T cells, which were replaced by gammadelta T-cell subsets (mainly
      Vgamma6+ gammadeltalowCCR2+CCR6-) actively producing IL-17A. Consistent with a
      proangiogenic role, gammadelta T cells promoted the formation of blood vessels in
      the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL
      17A+ gammadelta T cells could only be observed at the cancer stage (SCC), where
      HPV oncoproteins are highly expressed, supporting the clinical relevance of our
      observations in mice. Overall, our results suggest that HPV16 oncoproteins induce
      a reorganization of the local epithelial-associated gammadelta T-cell
      subpopulations, thereby promoting angiogenesis and cancer development.

PMID- 29073103
TI  - Packaging and transfer of mitochondrial DNA via exosomes regulate escape from
      dormancy in hormonal therapy-resistant breast cancer.
AB  - The horizontal transfer of mtDNA and its role in mediating resistance to therapy
      and an exit from dormancy have never been investigated. Here we identified the
      full mitochondrial genome in circulating extracellular vesicles (EVs) from
      patients with hormonal therapy-resistant (HTR) metastatic breast cancer. We
      generated xenograft models of HTR metastatic disease characterized by EVs in the
      peripheral circulation containing mtDNA. Moreover, these human HTR cells had
      acquired host-derived (murine) mtDNA promoting estrogen receptor-independent
      oxidative phosphorylation (OXPHOS). Functional studies identified cancer
      associated fibroblast (CAF)-derived EVs (from patients and xenograft models)
      laden with whole genomic mtDNA as a mediator of this phenotype. Specifically, the
      treatment of hormone therapy (HT)-naive cells or HT-treated metabolically dormant
      populations with CAF-derived mtDNAhi EVs promoted an escape from metabolic
      quiescence and HTR disease both in vitro and in vivo. Moreover, this phenotype
      was associated with the acquisition of EV mtDNA, especially in cancer stem-like
      cells, expression of EV mtRNA, and restoration of OXPHOS. In summary, we have
      demonstrated that the horizontal transfer of mtDNA from EVs acts as an oncogenic
      signal promoting an exit from dormancy of therapy-induced cancer stem-like cells
      and leading to endocrine therapy resistance in OXPHOS-dependent breast cancer.

PMID- 29073104
TI  - Human papillomavirus oncogenes reprogram the cervical cancer microenvironment
      independently of and synergistically with estrogen.
AB  - High-risk human papillomaviruses (HPVs) infect epithelial cells and are causally
      associated with cervical cancer, but HPV infection is not sufficient for
      carcinogenesis. Previously, we reported that estrogen signaling in the stromal
      tumor microenvironment is associated with cervical cancer maintenance and
      progression. We have now determined how HPV oncogenes and estrogen treatment
      affect genome-wide host gene expression in laser-captured regions of the cervical
      epithelium and stroma of untreated or estrogen-treated nontransgenic and HPV
      transgenic mice. HPV oncogene expression in the cervical epithelium elicited
      significant gene-expression changes in the proximal stromal compartment, and
      estrogen treatment uniquely affected gene expression in the cervical
      microenvironment of HPV-transgenic mice compared with nontransgenic mice. Several
      potential estrogen-induced paracrine-acting factors were identified in the
      expression profile of the cervical tumor microenvironment. The microenvironment
      of estrogen-treated HPV-transgenic mice was significantly enriched for
      chemokine/cytokine activity and inflammatory and immune functions associated with
      carcinogenesis. This inflammatory signature included several proangiogenic CXCR2
      receptor ligands. A subset of the same CXCR2 ligands was likewise increased in
      cocultures of early-passage cells from human cervical samples, with levels
      highest in cocultures of cervical fibroblasts and cancer-derived epithelial
      cells. Our studies demonstrate that high-risk HPV oncogenes profoundly reprogram
      the tumor microenvironment independently of and synergistically with estrogen.
      These observations illuminate important means by which HPVs can cause cancer
      through alterations in the tumor microenvironment.

PMID- 29073105
TI  - PAF promotes stemness and radioresistance of glioma stem cells.
AB  - An integrated genomic and functional analysis to elucidate DNA damage signaling
      factors promoting self-renewal of glioma stem cells (GSCs) identified
      proliferating cell nuclear antigen (PCNA)-associated factor (PAF) up-regulation
      in glioblastoma. PAF is preferentially overexpressed in GSCs. Its depletion
      impairs maintenance of self-renewal without promoting differentiation and reduces
      tumor-initiating cell frequency. Combined transcriptomic and metabolomic analyses
      revealed that PAF supports GSC maintenance, in part, by influencing DNA
      replication and pyrimidine metabolism pathways. PAF interacts with PCNA and
      regulates PCNA-associated DNA translesion synthesis (TLS); consequently, PAF
      depletion in combination with radiation generated fewer tumorspheres compared
      with radiation alone. Correspondingly, pharmacological impairment of DNA
      replication and TLS phenocopied the effect of PAF depletion in compromising GSC
      self-renewal and radioresistance, providing preclinical proof of principle that
      combined TLS inhibition and radiation therapy may be a viable therapeutic option
      in the treatment of glioblastoma multiforme (GBM).

PMID- 29073108
TI  - Visual perception as retrospective Bayesian decoding from high- to low-level
      features.
AB  - When a stimulus is presented, its encoding is known to progress from low- to high
      level features. How these features are decoded to produce perception is less
      clear, and most models assume that decoding follows the same low- to high-level
      hierarchy of encoding. There are also theories arguing for global precedence,
      reversed hierarchy, or bidirectional processing, but they are descriptive without
      quantitative comparison with human perception. Moreover, observers often inspect
      different parts of a scene sequentially to form overall perception, suggesting
      that perceptual decoding requires working memory, yet few models consider how
      working-memory properties may affect decoding hierarchy. We probed decoding
      hierarchy by comparing absolute judgments of single orientations and
      relative/ordinal judgments between two sequentially presented orientations. We
      found that lower-level, absolute judgments failed to account for higher-level,
      relative/ordinal judgments. However, when ordinal judgment was used to
      retrospectively decode memory representations of absolute orientations, striking
      aspects of absolute judgments, including the correlation and forward/backward
      aftereffects between two reported orientations in a trial, were explained. We
      propose that the brain prioritizes decoding of higher-level features because they
      are more behaviorally relevant, and more invariant and categorical, and thus
      easier to specify and maintain in noisy working memory, and that more reliable
      higher-level decoding constrains less reliable lower-level decoding.

PMID- 29073107
TI  - Spatial organization of a model 15-member human gut microbiota established in
      gnotobiotic mice.
AB  - Knowledge of the spatial organization of the gut microbiota is important for
      understanding the physical and molecular interactions among its members. These
      interactions are thought to influence microbial succession, community stability,
      syntrophic relationships, and resiliency in the face of perturbations. The
      complexity and dynamism of the gut microbiota pose considerable challenges for
      quantitative analysis of its spatial organization. Here, we illustrate an
      approach for addressing this challenge, using (i) a model, defined 15-member
      consortium of phylogenetically diverse, sequenced human gut bacterial strains
      introduced into adult gnotobiotic mice fed a polysaccharide-rich diet, and (ii)
      in situ hybridization and spectral imaging analysis methods that allow
      simultaneous detection of multiple bacterial strains at multiple spatial scales.
      Differences in the binding affinities of strains for substrates such as mucus or
      food particles, combined with more rapid replication in a preferred microhabitat,
      could, in principle, lead to localized clonally expanded aggregates composed of
      one or a few taxa. However, our results reveal a colonic community that is mixed
      at micrometer scales, with distinct spatial distributions of some taxa relative
      to one another, notably at the border between the mucosa and the lumen. Our data
      suggest that lumen and mucosa in the proximal colon should be conceptualized not
      as stratified compartments but as components of an incompletely mixed bioreactor.
      Employing the experimental approaches described should allow direct tests of
      whether and how specified host and microbial factors influence the nature and
      functional contributions of "microscale" mixing to the dynamic operations of the
      microbiota in health and disease.

PMID- 29073106
TI  - Cardiovascular homeostasis dependence on MICU2, a regulatory subunit of the
      mitochondrial calcium uniporter.
AB  - Comparative analyses of transcriptional profiles from humans and mice with
      cardiovascular pathologies revealed consistently elevated expression of MICU2, a
      regulatory subunit of the mitochondrial calcium uniporter complex. To determine
      if MICU2 expression was cardioprotective, we produced and characterized Micu2-/-
      mice. Mutant mice had left atrial enlargement and Micu2-/- cardiomyocytes had
      delayed sarcomere relaxation and cytosolic calcium reuptake kinetics, indicating
      diastolic dysfunction. RNA sequencing (RNA-seq) of Micu2-/- ventricular tissues
      revealed markedly reduced transcripts encoding the apelin receptor (Micu2-/- vs.
      wild type, P = 7.8 * 10-40), which suppresses angiotensin II receptor signaling
      via allosteric transinhibition. We found that Micu2-/- and wild-type mice had
      comparable basal blood pressures and elevated responses to angiotensin II
      infusion, but that Micu2-/- mice exhibited systolic dysfunction and 30% lethality
      from abdominal aortic rupture. Aneurysms and rupture did not occur with
      norepinephrine-induced hypertension. Aortic tissue from Micu2-/- mice had
      increased expression of extracellular matrix remodeling genes, while single-cell
      RNA-seq analyses showed increased expression of genes related to reactive oxygen
      species, inflammation, and proliferation in fibroblast and smooth muscle cells.
      We concluded that Micu2-/- mice recapitulate features of diastolic heart disease
      and define previously unappreciated roles for Micu2 in regulating angiotensin II
      mediated hypertensive responses that are critical in protecting the abdominal
      aorta from injury.

PMID- 29073109
TI  - Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula.
AB  - Hedonic hotspots are brain sites where particular neurochemical stimulations
      causally amplify the hedonic impact of sensory rewards, such as "liking" for
      sweetness. Here, we report the mapping of two hedonic hotspots in cortex, where
      mu opioid or orexin stimulations enhance the hedonic impact of sucrose taste. One
      hedonic hotspot was found in anterior orbitofrontal cortex (OFC), and another was
      found in posterior insula. A suppressive hedonic coldspot was also found in the
      form of an intervening strip stretching from the posterior OFC through the
      anterior and middle insula, bracketed by the two cortical hotspots. Opioid/orexin
      stimulations in either cortical hotspot activated Fos throughout a distributed
      "hedonic circuit" involving cortical and subcortical structures. Conversely,
      cortical coldspot stimulation activated circuitry for "hedonic suppression."
      Finally, food intake was increased by stimulations at several prefrontal cortical
      sites, indicating that the anatomical substrates in cortex for enhancing the
      motivation to eat are discriminable from those for hedonic impact.

PMID- 29073111
TI  - Perceiving social interactions in the posterior superior temporal sulcus.
AB  - Primates are highly attuned not just to social characteristics of individual
      agents, but also to social interactions between multiple agents. Here we report a
      neural correlate of the representation of social interactions in the human brain.
      Specifically, we observe a strong univariate response in the posterior superior
      temporal sulcus (pSTS) to stimuli depicting social interactions between two
      agents, compared with (i) pairs of agents not interacting with each other, (ii)
      physical interactions between inanimate objects, and (iii) individual animate
      agents pursuing goals and interacting with inanimate objects. We further show
      that this region contains information about the nature of the social interaction
      specifically, whether one agent is helping or hindering the other. This
      sensitivity to social interactions is strongest in a specific subregion of the
      pSTS but extends to a lesser extent into nearby regions previously implicated in
      theory of mind and dynamic face perception. This sensitivity to the presence and
      nature of social interactions is not easily explainable in terms of low-level
      visual features, attention, or the animacy, actions, or goals of individual
      agents. This region may underlie our ability to understand the structure of our
      social world and navigate within it.

PMID- 29073110
TI  - M344 promotes nonamyloidogenic amyloid precursor protein processing while
      normalizing Alzheimer's disease genes and improving memory.
AB  - Alzheimer's disease (AD) comprises multifactorial ailments for which current
      therapeutic strategies remain insufficient to broadly address the underlying
      pathophysiology. Epigenetic gene regulation relies upon multifactorial processes
      that regulate multiple gene and protein pathways, including those involved in AD.
      We therefore took an epigenetic approach where a single drug would simultaneously
      affect the expression of a number of defined AD-related targets. We show that the
      small-molecule histone deacetylase inhibitor M344 reduces beta-amyloid (Abeta),
      reduces tau Ser396 phosphorylation, and decreases both beta-secretase (BACE) and
      APOEepsilon4 gene expression. M344 increases the expression of AD-relevant genes:
      BDNF, alpha-secretase (ADAM10), MINT2, FE65, REST, SIRT1, BIN1, and ABCA7, among
      others. M344 increases sAPPalpha and CTFalpha APP metabolite production, both
      cleavage products of ADAM10, concordant with increased ADAM10 gene expression.
      M344 also increases levels of immature APP, supporting an effect on APP
      trafficking, concurrent with the observed increase in MINT2 and FE65, both shown
      to increase immature APP in the early secretory pathway. Chronic i.p. treatment
      of the triple transgenic (APPsw/PS1M146V/TauP301L) mice with M344, at doses as
      low as 3 mg/kg, significantly prevented cognitive decline evaluated by Y-maze
      spontaneous alternation, novel object recognition, and Barnes maze spatial memory
      tests. M344 displays short brain exposure, indicating that brief pulses of daily
      drug treatment may be sufficient for long-term efficacy. Together, these data
      show that M344 normalizes several disparate pathogenic pathways related to AD.
      M344 therefore serves as an example of how a multitargeting compound could be
      used to address the polygenic nature of multifactorial diseases.

PMID- 29073112
TI  - Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in
      oligodendrocytes and for myelination in vivo.
AB  - Oligodendrocytes in the central nervous system produce myelin, a lipid-rich,
      multilamellar sheath that surrounds axons and promotes the rapid propagation of
      action potentials. A critical component of myelin is myelin basic protein (MBP),
      expression of which requires anterograde mRNA transport followed by local
      translation at the developing myelin sheath. Although the anterograde motor
      kinesin KIF1B is involved in mbp mRNA transport in zebrafish, it is not entirely
      clear how mbp transport is regulated. From a forward genetic screen for
      myelination defects in zebrafish, we identified a mutation in actr10, which
      encodes the Arp11 subunit of dynactin, a critical activator of the retrograde
      motor dynein. Both the actr10 mutation and pharmacological dynein inhibition in
      zebrafish result in failure to properly distribute mbp mRNA in oligodendrocytes,
      indicating a paradoxical role for the retrograde dynein/dynactin complex in
      anterograde mbp mRNA transport. To address the molecular mechanism underlying
      this observation, we biochemically isolated reporter-tagged Mbp mRNA granules
      from primary cultured mammalian oligodendrocytes to show that they indeed
      associate with the retrograde motor complex. Next, we used live-cell imaging to
      show that acute pharmacological dynein inhibition quickly arrests Mbp mRNA
      transport in both directions. Chronic pharmacological dynein inhibition also
      abrogates Mbp mRNA distribution and dramatically decreases MBP protein levels.
      Thus, these cell culture and whole animal studies demonstrate a role for the
      retrograde dynein/dynactin motor complex in anterograde mbp mRNA transport and
      myelination in vivo.

PMID- 29073115
TI  - Correction for Piff et al., Higher social class predicts increased unethical
      behavior.

PMID- 29073116
TI  - Correction for Eissa et al., Cross-scale effects of neural interactions during
      human neocortical seizure activity.

PMID- 29073113
TI  - beta2-Adrenoceptor signaling in airway epithelial cells promotes eosinophilic
      inflammation, mucous metaplasia, and airway contractility.
AB  - The mostly widely used bronchodilators in asthma therapy are beta2-adrenoreceptor
      (beta2AR) agonists, but their chronic use causes paradoxical adverse effects. We
      have previously determined that beta2AR activation is required for expression of
      the asthma phenotype in mice, but the cell types involved are unknown. We now
      demonstrate that beta2AR signaling in the airway epithelium is sufficient to
      mediate key features of the asthmatic responses to IL-13 in murine models. Our
      data show that inhibition of beta2AR signaling with an aerosolized antagonist
      attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus
      production responses to IL-13, whereas treatment with an aerosolized agonist
      worsens these phenotypes, suggesting that beta2AR signaling on resident lung
      cells modulates the asthma phenotype. Labeling with a fluorescent beta2AR ligand
      shows the receptors are highly expressed in airway epithelium. In beta2AR-/-
      mice, transgenic expression of beta2ARs only in airway epithelium is sufficient
      to rescue IL-13-induced AHR, inflammation, and mucus production, and transgenic
      overexpression in WT mice exacerbates these phenotypes. Knockout of beta-arrestin
      2 (betaarr-2-/-) attenuates the asthma phenotype as in beta2AR-/- mice. In
      contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted
      by beta2AR signaling. Together, these results suggest beta2ARs on airway
      epithelial cells promote the asthma phenotype and that the proinflammatory
      pathway downstream of the beta2AR involves betaarr-2. These results identify
      beta2AR signaling in the airway epithelium as capable of controlling integrated
      responses to IL-13 and affecting the function of other cell types such as airway
      smooth muscle cells.

PMID- 29073117
TI  - Thoracoscopic purse-string suture technique for managing superior vena caval
      impalement from central venous catheterization.

PMID- 29073114
TI  - Pathogenesis of hypothyroidism-induced NAFLD is driven by intra- and extrahepatic
      mechanisms.
AB  - Hypothyroidism, a metabolic disease characterized by low thyroid hormone (TH) and
      high thyroid-stimulating hormone (TSH) levels in the serum, is strongly
      associated with nonalcoholic fatty liver disease (NAFLD). Hypothyroidism-induced
      NAFLD has generally been attributed to reduced TH signaling in the liver with a
      consequent decrease in lipid utilization. Here, we found that mildly hypothyroid
      mice develop NAFLD without down-regulation of hepatic TH signaling or decreased
      hepatic lipid utilization. NAFLD was induced by impaired suppression of adipose
      tissue lipolysis due to decreased insulin secretion and to a reduced response of
      adipose tissue itself to insulin. This condition leads to increased shuttling of
      fatty acids (FAs) to the liver, where they are esterified and accumulated as
      triglycerides. Lipid accumulation in the liver induces hepatic insulin
      resistance, which leads to impaired suppression of endogenous glucose production
      after feeding. Hepatic insulin resistance, synergistically with lowered insulin
      secretion, increases serum glucose levels, which stimulates de novo lipogenesis
      (DNL) in the liver. Up-regulation of DNL also contributes to NAFLD. In contrast,
      severely hypothyroid mice show down-regulation of TH signaling in their livers
      and profound suppression of adipose tissue lipolysis, which decreases delivery of
      FAs to the liver. The resulting lack of substrates for triglyceride
      esterification protects severely hypothyroid mice against NAFLD. Our findings
      demonstrate that NAFLD occurs when TH levels are mildly reduced, but,
      paradoxically, not when they are severely reduced. Our results show that the
      pathogenesis of hypothyroidism-induced NAFLD is both intra- and extrahepatic;
      they also reveal key metabolic differences between mild and severe
      hypothyroidism.

PMID- 29073118
TI  - Intrathoracic transmural esophageal perforation (Boerhaave syndrome): Challenges
      in management of the delayed presentation.

PMID- 29073119
TI  - Expression of Concern.

PMID- 29073120
TI  - Frailty in HIV infected people: a new risk factor for bone mineral density loss?:
      Erratum.

PMID- 29073122
TI  - Notes from the Field: Postflooding Leptospirosis - Louisiana, 2016.

PMID- 29073121
TI  - Transient Elastography (FibroScan) Performs Better Than Non-Invasive Markers in
      Assessing Liver Fibrosis and Cirrhosis in Autoimmune Hepatitis Patients.
AB  - BACKGROUND Autoimmune hepatitis (AIH) is an immune-mediated chronic liver disease
      that can lead to severe fibrosis and cirrhosis. Transient elastography (TE,
      FibroScan) can assess the fibrotic stages of chronic liver diseases by liver
      stiffness measurement (LSM). Studies on the diagnostic accuracy of FibroScan for
      the detection of fibrosis in AIH patients are still limited. MATERIAL AND METHODS
      This study enrolled 108 AIH patients who underwent liver biopsies. Using the
      METAVIR scoring system as the reference, Spearman's rank correlation was
      performed to explore the relationship between the markers and stages of fibrosis.
      The area under the receiver operating characteristic curve (AUROC) was used to
      evaluate the diagnostic accuracy. The optimal LSM cut-off values for predicting
      the stages of fibrosis were calculated. RESULTS LSM was superior to other non
      invasive markers in differentiating the stages of fibrosis in AIH patients. AUROC
      value of LSM was 0.885 for stage F2, 0.897 for stage F3, and 0.878 for stage F4.
      The optimal LSM cut-off value was 6.27 kPa for stage F2, 8.18 kPa for F3, and
      12.67 kPa for F4. CONCLUSIONS FibroScan is a valuable non-invasive method for the
      evaluation of liver fibrosis of AIH patients.

PMID- 29073123
TI  - Notes from the Field: Postexposure Prophylaxis for Rabies After Consumption of a
      Prepackaged Salad Containing a Bat Carcass - Florida, 2017.

PMID- 29073124
TI  - Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the
      Cause of an Outbreak - Liberia, 2017.
AB  - On April 25, 2017, a cluster of unexplained illness and deaths among persons who
      had attended a funeral during April 21-22 was reported in Sinoe County, Liberia
      (1). Using a broad initial case definition, 31 cases were identified, including
      13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases
      each were from Grand Bassa and Monsterrado counties, respectively. On May 5,
      2017, initial multipathogen testing of specimens from four fatal cases using the
      Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens.
      Subsequent testing using direct real-time polymerase chain reaction (PCR)
      confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and
      identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N.
      meningitidis was detected in specimens from 11 of the 13 patients who died; no
      specimens were available from the other two fatal cases. On May 16, 2017, the
      National Public Health Institute of Liberia and the Ministry of Health of Liberia
      issued a press release confirming serogroup C meningococcal disease as the cause
      of this outbreak in Liberia.

PMID- 29073125
TI  - Progress Toward Regional Measles Elimination - Worldwide, 2000-2016.
AB  - The fourth United Nations Millennium Development Goal, adopted in 2000, set a
      target to reduce child mortality by two thirds by 2015. One indicator of progress
      toward this target was measles vaccination coverage (1). In 2010, the World
      Health Assembly (WHA) set three milestones for measles control by 2015: 1)
      increase routine coverage with the first dose of a measles-containing vaccine
      (MCV1) among children aged 1 year to >=90% at the national level and to >=80% in
      every district; 2) reduce global annual measles incidence to <5 cases per million
      population; and 3) reduce global measles mortality by 95% from the 2000 estimate
      (2).* In 2012, WHA endorsed the Global Vaccine Action Plan,? with the objective
      of eliminating measles in four World Health Organization (WHO) regions by 2015
      and in five regions by 2020. Countries in all six WHO regions have adopted goals
      for measles elimination by or before 2020. Measles elimination is defined as the
      absence of endemic measles virus transmission in a region or other defined
      geographic area for >=12 months, in the presence of a high quality surveillance
      system that meets targets of key performance indicators. This report updates a
      previous report (3) and describes progress toward global measles control
      milestones and regional measles elimination goals during 2000-2016. During this
      period, annual reported measles incidence decreased 87%, from 145 to 19 cases per
      million persons, and annual estimated measles deaths decreased 84%, from 550,100
      to 89,780; measles vaccination prevented an estimated 20.4 million deaths.
      However, the 2015 milestones have not yet been met; only one WHO region has been
      verified as having eliminated measles. Improved implementation of elimination
      strategies by countries and their partners is needed, with focus on increasing
      vaccination coverage through substantial and sustained additional investments in
      health systems, strengthening surveillance systems, using surveillance data to
      drive programmatic actions, securing political commitment, and raising the
      visibility of measles elimination goals.

PMID- 29073127
TI  - Erratum: Vol. 66, No. 40.

PMID- 29073126
TI  - Notes from the Field: High Volume of Lyme Disease Laboratory Reporting in a Low
      Incidence State - Arkansas, 2015-2016.

PMID- 29073128
TI  - QuickStats: Percentage* of Adults Aged >=20 Years Who Reported Being Told by a
      Doctor or Health Professional to Increase Their Physical Activity,? by Age Group
      and Obesity StatusS - National Health and Nutrition Examination Survey, United
      States, 2011-2014.
AB  - During 2011-2014, 33.2% of adults aged >=20 years reported that a doctor or
      health professional told them to increase their physical activity. More than half
      (52.2%) of adults aged >=20 years with obesity reported that a doctor or health
      professional told them to increase their physical activity compared with less
      than a quarter (22.3%) of adults without obesity. This pattern remained the same
      for all age groups examined. For both adults with and without obesity, the
      proportion who reported being told to increase their physical activity increased
      with age.

PMID- 29073129
TI  - Receipt of Selected Preventive Health Services for Women and Men of Reproductive
      Age - United States, 2011-2013.
AB  - PROBLEM/CONDITION: Receipt of key preventive health services among women and men
      of reproductive age (i.e., 15-44 years) can help them achieve their desired
      number and spacing of healthy children and improve their overall health. The 2014
      publication Providing Quality Family Planning Services: Recommendations of CDC
      and the U.S. Office of Population Affairs (QFP) establishes standards for
      providing a core set of preventive services to promote these goals. These
      services include contraceptive care for persons seeking to prevent or delay
      pregnancy, pregnancy testing and counseling, basic infertility services for those
      seeking to achieve pregnancy, sexually transmitted disease (STD) services, and
      other preconception care and related preventive health services. QFP describes
      how to provide these services and recommends using family planning and other
      primary care visits to screen for and offer the full range of these services.
      This report presents baseline estimates of the use of these preventive services
      before the publication of QFP that can be used to monitor progress toward
      improving the quality of preventive care received by women and men of
      reproductive age. PERIOD COVERED: 2011-2013. DESCRIPTION OF THE SYSTEM: Three
      surveillance systems were used to document receipt of preventive health services
      among women and men of reproductive age as recommended in QFP. The National
      Survey of Family Growth (NSFG) collects data on factors that influence
      reproductive health in the United States since 1973, with a focus on fertility,
      sexual activity, contraceptive use, reproductive health care, family formation,
      child care, and related topics. NSFG uses a stratified, multistage probability
      sample to produce nationally representative estimates for the U.S. household
      population of women and men aged 15-44 years. This report uses data from the 2011
      2013 NSFG. The Pregnancy Risk Assessment Monitoring System (PRAMS) is an ongoing,
      state- and population-based surveillance system designed to monitor selected
      maternal behaviors and experiences that occur before, during, and shortly after
      pregnancy among women who deliver live-born infants in the United States. Annual
      PRAMS data sets are created and used to produce statewide estimates of
      preconception and perinatal health behaviors and experiences. This report uses
      PRAMS data for 2011-2012 from 11 states (Hawaii, Maine, Maryland, Michigan,
      Minnesota, Nebraska, New Jersey, Tennessee, Utah, Vermont, and West Virginia).
      The National Health Interview Survey (NHIS) is a nationally representative survey
      of noninstitutionalized civilians in the United States. NHIS collects data on a
      broad range of health topics, including the prevalence, distribution, and effects
      of illness and disability and the services rendered for or because of such
      conditions. Households are identified through a multistage probability household
      sampling design, and estimates are produced using weights that account for the
      sampling design, nonresponse, and poststratification adjustments. This report
      uses data from the 2013 NHIS for women aged 18-44 years. RESULTS: Many preventive
      health services recommended in QFP were not received by all women and men of
      reproductive age. For contraceptive services, including contraceptive counseling
      and advice, 46.5% of women aged 15-44 years at risk for unintended pregnancy
      received services in the past year, and 4.5% of men who had vaginal intercourse
      in the past year received services in that year. For sexually transmitted disease
      (STD) services, among all women aged 15-24 years who had oral, anal, or vaginal
      sex with an opposite sex partner in the past year, 37.5% were tested for
      chlamydia in that year. Among persons aged 15-44 years who were at risk because
      they were not in a mutually monogamous relationship during the past year, 45.3%
      of women were tested for chlamydia and 32.5% of men were tested for any STD in
      that year. For preconception care and related preventive health services, data
      from selected states indicated that 33.2% of women with a recent live birth
      (i.e., 2-9 months postpartum) talked with a health care professional about
      improving their health before their most recent pregnancy; of selected
      preconception counseling topics, the most frequently discussed was taking
      vitamins with folic acid before pregnancy (81.2%), followed by achieving a
      healthy weight before pregnancy (62.9%) and how drinking alcohol (60.3%) or
      smoking (58.2%) during pregnancy can affect a baby. Nationally, among women aged
      18-44 years irrespective of pregnancy status, 80.9% had their blood pressure
      checked by a health care professional and 31.7% received an influenza vaccine in
      the past year; 54.5% of those with high blood pressure were tested for diabetes,
      44.9% of those with obesity had a health care professional talk with them about
      their diet, and 55.2% of those who were current smokers had a health professional
      talk with them about their smoking in the past year. Among all women aged 21-44
      years, 81.6% received a Papanicolaou (Pap) test in the past 3 years. Receipt of
      certain preventive services varied by age and race/ethnicity. Among women with a
      recent live birth, the percentage of those who talked with a health care
      professional about improving their health before their most recent pregnancy
      increased with age (range: 25.9% and 25.2% for women aged <=19 and 20-24 years,
      respectively, to 35.9% and 37.8% for women aged 25-34 and >=35 years,
      respectively). Among women with a recent live birth, the percentage of those who
      talked with a health care professional about improving their health before their
      most recent pregnancy was higher for non-Hispanic white (white) (35.2%) compared
      with non-Hispanic black (black) (30.0%) and Hispanic (26.0%) women. Conversely,
      across most STD screening services evaluated, testing was highest among black
      women and men and lowest among their white counterparts. Receipt of many
      preventive services recommended in QFP increased consistently across categories
      of family income and continuity of health insurance coverage. Prevalence of
      service receipt was highest among women in the highest family income category
      (>400% of federal poverty level [FPL]) and among women with insurance coverage
      for each of the following: contraceptive services among women at risk for
      unintended pregnancy; medical services beyond advice to help achieve pregnancy;
      vaccinations (hepatitis B and human papillomavirus [HPV], ever; tetanus, past 10
      years; influenza, past year); discussions with a health care professional about
      improving health before pregnancy and taking vitamins with folic acid; blood
      pressure and diabetes screening; discussions with a health care professional in
      the past year about diet, among those with obesity; discussions with a health
      care professional in the past year about smoking, among current smokers; Pap
      tests within the past 3 years; and mammograms within the past 2 years.
      INTERPRETATION: Before 2014, many women and men of reproductive age were not
      receiving several of the preventive services recommended for them in QFP.
      Although differences existed by age and race/ethnicity, across the range of
      recommended services, receipt was consistently lower among women and men with
      lower family income and greater instability in health insurance coverage. PUBLIC
      HEALTH ACTION: Information in this report on baseline receipt during 2011-2013 of
      preventive services for women and men of reproductive age can be used to target
      improvements in the use of recommended services through the development
      ofresearch priorities, information for decision makers, and public health
      practice. Health care administrators and practitioners can use the information to
      identify subpopulations with the greatest need for preventive services and make
      informed decisions on resource allocation. Public health researchers can use the
      information to guide research on the determinants of service use and factors that
      might increase use of preventive services. Policymakers can use this information
      to evaluate the impact of policy changes and assess resource needs for effective
      programs, research, and surveillance on the use of preventive health services for
      women and men of reproductive age.

PMID- 29073131
TI  - Human action recognition based on kinematic similarity in real time.
AB  - Human action recognition using 3D pose data has gained a growing interest in the
      field of computer robotic interfaces and pattern recognition since the
      availability of hardware to capture human pose. In this paper, we propose a fast,
      simple, and powerful method of human action recognition based on human kinematic
      similarity. The key to this method is that the action descriptor consists of
      joints position, angular velocity and angular acceleration, which can meet the
      different individual sizes and eliminate the complex normalization. The angular
      parameters of joints within a short sliding time window (approximately 5 frames)
      around the current frame are used to express each pose frame of human action
      sequence. Moreover, three modified KNN (k-nearest-neighbors algorithm)
      classifiers are employed in our method: one for achieving the confidence of every
      frame in the training step, one for estimating the frame label of each
      descriptor, and one for classifying actions. Additional estimating of the frame's
      time label makes it possible to address single input frames. This approach can be
      used on difficult, unsegmented sequences. The proposed method is efficient and
      can be run in real time. The research shows that many public datasets are
      irregularly segmented, and a simple method is provided to regularize the
      datasets. The approach is tested on some challenging datasets such as MSR
      Action3D, MSRDailyActivity3D, and UTD-MHAD. The results indicate our method
      achieves a higher accuracy.

PMID- 29073130
TI  - Non-alcoholic fatty liver disease and the development of nephrolithiasis: A
      cohort study.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation or
      precursor of metabolic syndrome, may increase nephrolithiasis, a renal
      manifestation of insulin resistance, but the prospective association between
      NAFLD and incident nephrolithiasis has not been evaluated. We examined the
      association of NAFLD with the development of nephrolithiasis in a large cohort of
      Korean men and women. METHODS: We performed a cohort study of 208,578 Korean
      adults who underwent a health checkup examination between January 2002 and
      December 2014 and were followed-up annually or biennially through December 2014.
      NAFLD was defined as the presence of fatty liver in the absence of excessive
      alcohol use or other identifiable causes. Fatty liver and nephrolithiasis were
      determined based on ultrasonographic findings. We used a parametric Cox model to
      estimate the adjusted hazard ratios (HRs) of nephrolithiasis according to the
      presence of NAFLD. RESULTS: During 1,054,887.6 person-year of follow-up, 16,442
      participants developed nephrolithiasis. After adjusting for age, center, year of
      screening exam, smoking status, alcohol intake, physical activity, education
      level, body mass index, history of hypertension and diabetes, HOMA-IR, uric acid
      and C-reactive protein, male participants with NAFLD had a significantly
      increased risk of nephrolithiasis than those without NAFLD (adjusted HR 1.17, 95%
      CI 1.06-1.30). However, no association between NAFLD and nephrolithiasis was
      observed in women (adjusted HR 0.97, 95% CI 0.81-1.16). CONCLUSIONS: In this
      large cohort study of young and middle-aged Koreans, NAFLD was significantly
      associated with an increased incidence of nephrolithiasis in men but not in
      women.

PMID- 29073132
TI  - Patterns, factors associated and morbidity burden of asthma in India.
AB  - BACKGROUND: Asthma is a non-curable but preventable disease, responsible for
      higher morbidity worldwide. According to recent WHO report, nearly 235 million
      people are suffering from asthma leading to 383000 deaths in 2015. The burden of
      asthma morbidity is higher in developed countries and is increasing in developing
      countries. OBJECTIVE: The present study was aimed at studying the change in
      prevalence rate of asthma, associated risk factors and estimation of morbidity
      burden and avoidable cases of asthma in India. METHODS: The second round of
      Indian Human Development Survey (IHDS-II), 2011-12, was used for the study. For
      the present study, asthma was defines as ever diagnosed with asthma or having
      cough with short breath. Multiple-logistic regression was used to identify the
      possible risk factors associated with prevalence of reporting asthma. Population
      attributable fractions (PAFs) were computed to estimate the overall and risk
      factors specific burden of morbidity due to asthma using the extrapolated
      population of year 2015 using 2011 census. RESULTS: Overall prevalence rate of
      asthma increased from 41.9 (per 1000 population) in 2004-05 to 54.9 (per 1000
      population) in 2011-12. The prevalence rate of reporting asthma was higher in
      poorer states compared to richer states, and also varied by sub-geographies, with
      higher prevalence rate in northern states of the country and lower rates in north
      eastern states of the country. The odds of reporting asthma was higher for
      younger and older ages, individual with fewer years of schooling (OR: 1.41; 95%
      CI: 1.21-1.64) for individual with zero years of schooling compared to those with
      11 or more years of schooling, individual from lower economic status, individual
      living in household using unclean fuels (OR:1.21; 95% CI: 1.08-1.34) and smokers
      (OR: 1.34; 95% CI: 1.17-1.55) compared to their counterparts. In the year 2015,
      the overall morbidity burden of asthma was estimated at nearly 65 million and
      more than 82 thousand deaths were attributed due to asthma. The burden was
      highest among individuals living in households using solid fuels (firewood~80%,
      Kerosene~78%). One-third of the cases could be eliminated by minimising the use
      of any solid fuels. Around 17% of all the asthma cases in population could be
      attributed to underweight. CONCLUSION: Eliminating the modifiable risk factors
      could help reduce in huge amount of asthma cases for example by providing
      education, cessation in smoking, and schemes like Pradhan Mantri Ujjwala Yojana
      (PMUY), by providing clean fuel (LPG) to poor and vulnerable households.

PMID- 29073133
TI  - Correction: Quantifying underreporting of law-enforcement-related deaths in
      United States vital statistics and news-media-based data sources: A capture
      recapture analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002399.].

PMID- 29073134
TI  - New paths for PLOS Neglected Tropical Diseases: Continuing a tradition of
      innovation and commitment to the poor.

PMID- 29073135
TI  - The GYF domain protein PSIG1 dampens the induction of cell death during plant
      pathogen interactions.
AB  - The induction of rapid cell death is an effective strategy for plants to restrict
      biotrophic and hemi-biotrophic pathogens at the infection site. However,
      activation of cell death comes at a high cost, as dead cells will no longer be
      available for defense responses nor general metabolic processes. In addition,
      necrotrophic pathogens that thrive on dead tissue, take advantage of cell death
      triggering mechanisms. Mechanisms by which plants solve this conundrum remain
      described. Here, we identify PLANT SMY2-TYPE ILE-GYF DOMAIN-CONTAINING PROTEIN 1
      (PSIG1) and show that PSIG1 helps to restrict cell death induction during
      pathogen infection. Inactivation of PSIG1 does not result in spontaneous lesions,
      and enhanced cell death in psig1 mutants is independent of salicylic acid (SA)
      biosynthesis or reactive oxygen species (ROS) production. Moreover, PSIG1
      interacts with SMG7, which plays a role in nonsense-mediated RNA decay (NMD), and
      the smg7-4 mutant allele mimics the cell death phenotype of the psig1 mutants.
      Intriguingly, the psig1 mutants display enhanced susceptibility to the hemi
      biotrophic bacterial pathogen. These findings point to the existence and
      importance of the SA- and ROS-independent cell death constraining mechanism as a
      part of the plant immune system.

PMID- 29073136
TI  - A bacterial toxin-antitoxin module is the origin of inter-bacterial and inter
      kingdom effectors of Bartonella.
AB  - Host-targeting type IV secretion systems (T4SS) evolved from conjugative T4SS
      machineries that mediate interbacterial plasmid transfer. However, the origins of
      effectors secreted by these virulence devices have remained largely elusive.
      Previous work showed that some effectors exhibit homology to toxins of bacterial
      toxin-antitoxin modules, but the evolutionary trajectories underlying these ties
      had not been resolved. We previously reported that FicT toxins of FicTA toxin
      antitoxin modules disrupt cellular DNA topology via their enzymatic FIC
      (filamentation induced by cAMP) domain. Intriguingly, the FIC domain of the FicT
      toxin VbhT of Bartonella schoenbuchensis is fused to a type IV secretion signal
      the BID (Bep intracellular delivery) domain-similar to the Bartonella effector
      proteins (Beps) that are secreted into eukaryotic host cells via the host
      targeting VirB T4SS. In this study, we show that the VbhT toxin is an
      interbacterial effector protein secreted via the conjugative Vbh T4SS that is
      closely related to the VirB T4SS and encoded by plasmid pVbh of B.
      schoenbuchensis. We therefore propose that the Vbh T4SS together with its
      effector VbhT represent an evolutionary missing link on a path that leads from a
      regular conjugation system and FicTA toxin-antitoxin modules to the VirB T4SS and
      the Beps. Intriguingly, phylogenetic analyses revealed that the fusion of FIC and
      BID domains has probably occurred independently in VbhT and the common ancestor
      of the Beps, suggesting parallel evolutionary paths. Moreover, several other
      examples of TA module toxins that are bona fide substrates of conjugative T4SS
      indicate that their recruitment as interbacterial effectors is prevalent and
      serves yet unknown biological functions in the context of bacterial conjugation.
      We propose that the adaptation for interbacterial transfer favors the exaptation
      of FicT and other TA module toxins as inter-kingdom effectors and may thus
      constitute an important stepping stone in the evolution of host-targeted effector
      proteins.

PMID- 29073137
TI  - Integration of enteric fever surveillance into the WHO-coordinated Invasive
      Bacterial-Vaccine Preventable Diseases (IB-VPD) platform: A low cost approach to
      track an increasingly important disease.
AB  - BACKGROUND: Lack of surveillance systems and accurate data impede evidence-based
      decisions on treatment and prevention of enteric fever, caused by Salmonella
      Typhi/Paratyphi. The WHO coordinates a global Invasive Bacterial-Vaccine
      Preventable Diseases (IB-VPD) surveillance network but does not monitor enteric
      fever. We evaluated the feasibility and sustainability of integrating enteric
      fever surveillance into the ongoing IB-VPD platform. METHODOLOGIES: The IB-VPD
      surveillance system uses WHO definitions to enroll 2-59 month children
      hospitalized with possible pneumonia, sepsis or meningitis. We expanded this
      surveillance system to additionally capture suspect enteric fever cases during
      2012-2016, in two WHO sentinel hospitals of Bangladesh, by adding inclusion
      criteria of fever >=102 degrees F for >=3 days, irrespective of other
      manifestations. Culture-positive enteric fever cases from in-patient departments
      (IPD) detected in the hospital laboratories but missed by the expanded
      surveillance, were also enrolled to assess completion. Costs for this integration
      were calculated for the additional personnel and resources required. PRINCIPAL
      FINDINGS: In the IB-VPD surveillance, 5,185 cases were enrolled; 3% (N =
      171/5185) were positive for microbiological growth, of which 55% (94/171) were
      culture-confirmed cases of enteric fever (85 Typhi and 9 Paratyphi A). The added
      inclusion criteria for enteric fever enrolled an additional 1,699 cases; 22%
      (358/1699) were positive, of which 85% (349/358) were enteric fever cases (305
      Typhi and 44 Paratyphi A). Laboratory surveillance of in-patients of all ages
      enrolled 311 additional enteric fever cases (263 Typhi and 48 Paratyphi A); 9%
      (28/311) were 2-59 m and 91% (283/311) >59 m. Altogether, 754 (94+349+311)
      culture-confirmed enteric fever cases were found, of which 471 were 2-59 m. Of
      these 471 cases, 94% (443/471) were identified through the hospital surveillances
      and 6% (28/471) through laboratory results. Twenty-three percent (170/754) of all
      cases were children <2 years. Additional cost for the integration was USD
      44,974/year, a 27% increase to the IB-VPD annual expenditure. CONCLUSION: In a
      setting where enteric disease is a substantial public health problem, we could
      integrate enteric fever surveillance into the standard IB-VPD surveillance
      platform at a modest cost.

PMID- 29073138
TI  - Why reinvent the wheel? Lessons in schistosomiasis control from the past.
AB  - Schistosomiasis has been of concern to local health authorities for most of the
      last century, and in spite of a lack of effective chemotherapy, the disease was
      dealt with quite effectively in many endemic countries by snail control and
      environmental management [1]. Much of this work was reported in journals prior to
      the electronic era but, sadly, seems to have been subsequently ignored. For many
      years, there followed a global hiatus on schistosomiasis control, and much of the
      local expertise was lost, but many things have changed more recently, mainly with
      the advent of generic and affordable praziquantel. With the increased
      availability of this drug, there has been an increasing interest in readdressing
      schistosomes as well as other neglected tropical diseases (NTDs). The strategic
      approach for this had been based almost exclusively on chemotherapy. Recently,
      however, questions arose about this strategy with evidence that chemotherapy
      alone was not succeeding [2]. Additional strategies were needed, and the "Towards
      Elimination of Schistosomiasis" (TES) 2017 Conference in Cameroon stressed an
      integrated PHASE strategy. This was in line with the WHO-NTD and WHO-AFRO 2014
      2020 Regional Strategy on NTDs and directed emphasis on transmission control.
      Subsequently, this emphasis was discussed in a comprehensive review [3] that
      stressed the importance of such additions to any elimination programme. In
      reality, this means focusing on the aquatic snail hosts where and when
      transmission occurs, defining other risk factors such as water contact and
      latrine design and identifying improved sanitation and health education as
      essential components for elimination. For schistosomiasis reduction during the
      mid-20th century, transmission control was used extensively, but these facts are
      not well reported. Recent reviews have attempted to cover previous research
      [4,5], but sadly, they have left major knowledge gaps, particularly from Africa.
      These omissions also occurred in a recent WHO pamphlet on molluscicides [6].
      Sadly, search engines used to retrieve information appear to miss much done by 5
      African research institutes active from 1950 to 1990. It seems appropriate to
      take a look back to a time when fieldwork was a focus of research and
      transmission control was emphasised.

PMID- 29073139
TI  - Composition of the Schistosoma mansoni worm secretome: Identification of immune
      modulatory Cyclophilin A.
AB  - The helminth Schistosoma mansoni modulates the infected host's immune system to
      facilitate its own survival, by producing excretory/secretory molecules that
      interact with a variety of the host's cell types including those of the immune
      system. Herein, we characterise the S. mansoni adult male worm secretome and
      identify 111 proteins, including 7 vaccine candidates and several molecules with
      potential immunomodulatory activity. Amongst the molecules present in the
      secretome, a 17-19kDa protein analogous to human cyclophilin A was identified.
      Given the ability of cyclophilin A to modulate the immune system by regulating
      antigen presenting cell activity, we sought to determine whether recombinant S.
      mansoni Cyclophilin A (rSmCypA) is capable of modulating bone-marrow derived
      dendritic cell (BMDC) and T cell responses under in vitro conditions. rSmCypA was
      enzymatically active and able to alter the pro-inflammatory cytokine profile of
      LPS-activated dendritic cells. rSmCypA also modulated DC function in the
      induction of CD4+ T cell proliferation with a preferential expansion of Treg
      cells. This work demonstrates the unique protein composition of the S. mansoni
      male worm secretome and immunomodulatory activity of S. mansoni Cyclophilin A.

PMID- 29073140
TI  - Volume-outcome revisited: The effect of hospital and surgeon volumes on multiple
      outcome measures in oesophago-gastric cancer surgery.
AB  - BACKGROUND: Most studies showing a volume outcome effect in resection surgery for
      oesophago-gastric cancer were conducted before the centralisation of clinical
      services. This study evaluated the relation between hospital- and surgeon volume
      and different risk-adjusted outcomes after oesophago-gastric (OG) cancer surgery
      in England between 2011 and 2013. METHODS: In data from the National Oesophago
      Gastric Cancer Audit from the UK, multivariable random-effects logistic
      regression models were used to quantify the effect of surgeon and hospital volume
      on three outcomes: 30-day and 90-day mortality and anastomotic leakage. The
      models included patient risk factors to adjust for differences in case-mix among
      hospitals and surgeons. The between-cluster heterogeneity was estimated with the
      median odds ratio (MOR). RESULTS: The study included patients treated at 42
      hospitals and 329 surgeons. The median (interquartile range) of the annual
      hospital and surgeon volumes were 110 patients (82 to 137) and 13 patients (8 to
      19), respectively. The overall rates for 30-day and 90-day mortality were 2.3%
      and 4.4% respectively, and the anastomotic leakage was 6.3%. Higher hospital
      volume was associated with lower 30-day mortality (OR: 0.94; 95% CI: 0.91-0.98)
      and lower anastomotic leakage rates (OR: 0.96; 95% CI: 0.93-0.98) but not 90-day
      mortality. Higher surgeon volume was only associated with lower anastomotic
      leakage rates (OR: 0.81; 95% CI: 0.72-0.92). Hospital volume explained a part of
      the between-hospital variation in 30-day mortality whereas surgeon volume
      explained part of the between-hospital variation in anastomotic leakage.
      CONCLUSIONS: In the setting of centralized O-G cancer surgery in England, we
      could still observe an effect of volume on short-term outcomes. However, the
      effect is inconsistent, depending on the type of outcome measure under
      consideration, and much smaller than in previous studies. Efforts to centralise O
      G cancer services further should carefully address the effects of both hospital
      and surgeon volume on the range of outcome measures that are relevant to
      patients.

PMID- 29073141
TI  - Genomic regions associated with susceptibility to Barrett's esophagus and
      esophageal adenocarcinoma in African Americans: The cross BETRNet admixture
      study.
AB  - BACKGROUND: Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) are far
      more prevalent in European Americans than in African Americans. Hypothesizing
      that this racial disparity in prevalence might represent a genetic
      susceptibility, we used an admixture mapping approach to interrogate disease
      association with genomic differences between European and African ancestry.
      METHODS: Formalin fixed paraffin embedded samples were identified from 54 African
      Americans with BE or EAC through review of surgical pathology databases at
      participating Barrett's Esophagus Translational Research Network (BETRNet)
      institutions. DNA was extracted from normal tissue, and genotyped on the Illumina
      OmniQuad SNP chip. Case-only admixture mapping analysis was performed on the data
      from both all 54 cases and also on a subset of 28 cases with high genotyping
      quality. Haplotype phases were inferred with Beagle 3.3.2, and local African and
      European ancestries were inferred with SABER plus. Disease association was tested
      by estimating and testing excess European ancestry and contrasting it to excess
      African ancestry. RESULTS: Both datasets, the 54 cases and the 28 cases,
      identified two admixture regions. An association of excess European ancestry on
      chromosome 11p reached a 5% genome-wide significance threshold, corresponding to 
      log10(P) = 4.28. A second peak on chromosome 8q reached -log10(P) = 2.73. The
      converse analysis examining excess African ancestry found no genetic regions with
      significant excess African ancestry associated with BE and EAC. On average, the
      regions on chromosomes 8q and 11p showed excess European ancestry of 15% and 20%,
      respectively. CONCLUSIONS: Chromosomal regions on 11p15 and 8q22-24 are
      associated with excess European ancestry in African Americans with BE and EAC.
      Because GWAS have not reported any variants in these two regions, low frequency
      and/or rare disease associated variants that confer susceptibility to developing
      BE and EAC may be driving the observed European ancestry association evidence.

PMID- 29073143
TI  - BBMerge - Accurate paired shotgun read merging via overlap.
AB  - Merging paired-end shotgun reads generated on high-throughput sequencing
      platforms can substantially improve various subsequent bioinformatics processes,
      including genome assembly, binning, mapping, annotation, and clustering for
      taxonomic analysis. With the inexorable growth of sequence data volume and CPU
      core counts, the speed and scalability of read-processing tools becomes ever-more
      important. The accuracy of shotgun read merging is crucial as well, as errors
      introduced by incorrect merging percolate through to reduce the quality of
      downstream analysis. Thus, we designed a new tool to maximize accuracy and
      minimize processing time, allowing the use of read merging on larger datasets,
      and in analyses highly sensitive to errors. We present BBMerge, a new merging
      tool for paired-end shotgun sequence data. We benchmark BBMerge by comparison
      with eight other widely used merging tools, assessing speed, accuracy and
      scalability. Evaluations of both synthetic and real-world datasets demonstrate
      that BBMerge produces merged shotgun reads with greater accuracy and at higher
      speed than any existing merging tool examined. BBMerge also provides the ability
      to merge non-overlapping shotgun read pairs by using k-mer frequency information
      to assemble the unsequenced gap between reads, achieving a significantly higher
      merge rate while maintaining or increasing accuracy.

PMID- 29073142
TI  - Elevation in and persistence of multiple urinary biomarkers indicative of
      oxidative DNA stress and inflammation: Toxicological implications of maleic acid
      consumption using a rat model.
AB  - Maleic acid (MA), an intermediate reagent used in many industrial products,
      instigated public health concerns in Taiwan when it was used to adulterate an
      array of starch-based delicacies to improve texture and storage time. Established
      studies reported that exposure to high concentrations of MA induce renal injury;
      little is known whether oxidative stress is induced at a relative low dose. This
      study aims to investigate the effect of oral single dose exposure of MA on the
      status of oxidative stress and inflammation. Single dose of MA at 0, 6 and 60
      mg/kg (control, low- and high-dose groups, respectively) were orally administered
      to adult male and female rats. Urine samples were collected and analyzed to
      measure 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2alpha (8
      IsoPGF2alpha), 8-nitroguanine (8-NO2Gua) and N-acetyl-S-(tetrahydro-5-hydroxy-2
      pentyl-3-furanyl)-L-cysteine (HNE-MA) using LC-MS/MS. Results revealed that oral
      consumption of MA induced oxidative DNA damage and lipid peroxidation, as
      demonstrated by the statistically significant increases in urinary levels of 8
      NO2Gua, 8-OHdG, and 8-isoPGF2alpha, in high-dosed male rats within 12 h of oral
      gavage (p < 0.05). Additionally, increases in concentration of these biomarkers
      persist for days after consumption; male rats appear to be more sensitive to
      oxidative burden compared to their counterparts. The aforementioned findings
      could help elucidate the mechanisms through which nephrotoxicity occur.

PMID- 29073144
TI  - The socio-economic burden of human African trypanosomiasis and the coping
      strategies of households in the South Western Kenya foci.
AB  - INTRODUCTION: Human African Trypanosomiasis (HAT), a disease caused by protozoan
      parasites transmitted by tsetse flies, is an important neglected tropical disease
      endemic in remote regions of sub-Saharan Africa. Although the determination of
      the burden of HAT has been based on incidence, mortality and morbidity rates, the
      true burden of HAT goes beyond these metrics. This study sought to establish the
      socio-economic burden that households with HAT faced and the coping strategies
      they employed to deal with the increased burden. MATERIALS AND METHODS: A mixed
      methods approach was used and data were obtained through: review of hospital
      records; structured interviews (152); key informant interviews (11); case
      narratives (12) and focus group discussions (15) with participants drawn from
      sleeping sickness patients in the south western HAT foci in Kenya. Quantitative
      data were analysed using descriptive statistics while qualitative data was
      analysed based on emerging themes. RESULTS: Socio-economic impacts included,
      disruption of daily activities, food insecurity, neglect of homestead, poor
      academic performance/school drop-outs and death. Delayed diagnosis of HAT caused
      93% of the affected households to experience an increase in financial expenditure
      (ranging from US$ 60-170) in seeking treatment. Out of these, 81.5% experienced
      difficulties in raising money for treatment resorting to various ways of raising
      it. The coping strategies employed to deal with the increased financial
      expenditure included: sale of agricultural produce (64%); seeking assistance from
      family and friends (54%); sale/lease of family assets (22%); seeking credit (22%)
      and use of personal savings (17%). CONCLUSION AND RECOMMENDATION: Coping
      strategies outlined in this study impacted negatively on the affected households
      leading to further food insecurity and impoverishment. Calculation of the true
      burden of disease needs to go beyond incidence, mortality and morbidity rates to
      capture socio-economic variables entailed in seeking treatment and coping
      strategies of HAT affected households.

PMID- 29073145
TI  - The cost and cost-effectiveness of rapid testing strategies for yaws diagnosis
      and surveillance.
AB  - BACKGROUND: Yaws is a non-venereal treponemal infection caused by Treponema
      pallidum subspecies pertenue. The disease is targeted by WHO for eradication by
      2020. Rapid diagnostic tests (RDTs) are envisaged for confirmation of clinical
      cases during treatment campaigns and for certification of the interruption of
      transmission. Yaws testing requires both treponemal (trep) and non-treponemal
      (non-trep) assays for diagnosis of current infection. We evaluate a sequential
      testing strategy (using a treponemal RDT before a trep/non-trep RDT) in terms of
      cost and cost-effectiveness, relative to a single-assay combined testing strategy
      (using the trep/non-trep RDT alone), for two use cases: individual diagnosis and
      community surveillance. METHODS: We use cohort decision analysis to examine the
      diagnostic and cost outcomes. We estimate cost and cost-effectiveness of the
      alternative testing strategies at different levels of prevalence of past/current
      infection and current infection under each use case. We take the perspective of
      the global yaws eradication programme. We calculate the total number of correct
      diagnoses for each strategy over a range of plausible prevalences. We employ
      probabilistic sensitivity analysis (PSA) to account for uncertainty and report
      95% intervals. RESULTS: At current prices of the treponemal and trep/non-trep
      RDTs, the sequential strategy is cost-saving for individual diagnosis at
      prevalence of past/current infection less than 85% (81-90); it is cost-saving for
      surveillance at less than 100%. The threshold price of the trep/non-trep RDT
      (below which the sequential strategy would no longer be cost-saving) is US$ 1.08
      (1.02-1.14) for individual diagnosis at high prevalence of past/current infection
      (51%) and US$ 0.54 (0.52-0.56) for community surveillance at low prevalence
      (15%). DISCUSSION: We find that the sequential strategy is cost-saving for both
      diagnosis and surveillance in most relevant settings. In the absence of evidence
      assessing relative performance (sensitivity and specificity), cost-effectiveness
      is uncertain. However, the conditions under which the combined test only strategy
      might be more cost-effective than the sequential strategy are limited. A cheaper
      trep/non-trep RDT is needed, costing no more than US$ 0.50-1.00, depending on the
      use case. Our results will help enhance the cost-effectiveness of yaws programmes
      in the 13 countries known to be currently endemic. It will also inform efforts in
      the much larger group of 71 countries with a history of yaws, many of which will
      have to undertake surveillance to confirm the interruption of transmission.

PMID- 29073147
TI  - Molecular characterization of three Rhesus glycoproteins from the gills of the
      African lungfish, Protopterus annectens, and effects of aestivation on their mRNA
      expression levels and protein abundance.
AB  - African lungfishes are ammonotelic in water. They can aestivate for long periods
      on land during drought. During aestivation, the gills are covered with dried
      mucus and ammonia excretion ceases. In fishes, ammonia excretion through the
      gills involves Rhesus glycoproteins (RhGP/Rhgp). This study aimed to obtain the
      complete cDNA coding sequences of rhgp from the gills of Protopterus annectens,
      and to determine their branchial mRNA and protein expression levels during the
      induction, maintenance and arousal phases of aestivation. Three isoforms of rhgp
      (rhag, rhbg and rhcg) were obtained in the gills of P. annectens. Their complete
      cDNA coding sequences ranged between 1311 and 1398 bp, coding for 436 to 465
      amino acids with estimated molecular masses between 46.8 and 50.9 kDa.
      Dendrogramic analyses indicated that Rhag was grouped closer to fishes, while
      Rhbg and Rhcg were grouped closer to tetrapods. During the induction phase, the
      protein abundance of Rhag, but not its transcript level, was down-regulated in
      the gills, suggesting that there could be a decrease in the release of ammonia
      from the erythrocytes to the plasma. Furthermore, the branchial transcript levels
      of rhbg and rhcg decreased significantly, in preparation for the subsequent
      shutdown of gill functions. During the maintenance phase, the branchial
      expression levels of rhag/Rhag, rhbg/Rhbg and rhcg/Rhcg decreased significantly,
      indicating that their transcription and translation were down-regulated. This
      could be part of an overall mechanism to shut down branchial functions and save
      metabolic energy used for transcription and translation. It could also be
      regarded as an adaptive response to stop ammonia excretion. During the arousal
      phase, it is essential for the lungfish to regain the ability to excrete ammonia.
      Indeed, the protein abundance of Rhag, Rhbg and Rhcg recovered to the
      corresponding control levels after 1 day or 3 days of recovery from 6 months of
      aestivation.

PMID- 29073146
TI  - Unified thalamic model generates multiple distinct oscillations with state
      dependent entrainment by stimulation.
AB  - The thalamus plays a critical role in the genesis of thalamocortical
      oscillations, yet the underlying mechanisms remain elusive. To understand whether
      the isolated thalamus can generate multiple distinct oscillations, we developed a
      biophysical thalamic model to test the hypothesis that generation of and
      transition between distinct thalamic oscillations can be explained as a function
      of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent
      synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms
      (delta, sleep spindle, alpha and gamma oscillations) that span the physiological
      states corresponding to different arousal levels from deep sleep to focused
      attention. Our simulation results indicate that generation of these distinct
      thalamic oscillations is a result of both intrinsic oscillatory cellular
      properties and specific network connectivity patterns. We then systematically
      varied the ACh/NE and input levels to generate a complete map of the different
      oscillatory states and their transitions. Lastly, we applied periodic stimulation
      to the thalamic network and found that entrainment of thalamic oscillations is
      highly state-dependent. Our results support the hypothesis that ACh/NE modulation
      and afferent excitation define thalamic oscillatory states and their response to
      brain stimulation. Our model proposes a broader and more central role of the
      thalamus in the genesis of multiple distinct thalamo-cortical rhythms than
      previously assumed.

PMID- 29073148
TI  - Age-dependent gene expression in the inner ear of big brown bats (Eptesicus
      fuscus).
AB  - For echolocating bats, hearing is essential for survival. Specializations for
      detecting and processing high frequency sounds are apparent throughout their
      auditory systems. Recent studies on echolocating mammals have reported evidence
      of parallel evolution in some hearing-related genes in which distantly related
      groups of echolocating animals (bats and toothed whales), cluster together in
      gene trees due to apparent amino acid convergence. However, molecular adaptations
      can occur not only in coding sequences, but also in the regulation of gene
      expression. The aim of this study was to examine the expression of hearing
      related genes in the inner ear of developing big brown bats, Eptesicus fuscus,
      during the period in which echolocation vocalizations increase dramatically in
      frequency. We found that seven genes were significantly upregulated in juveniles
      relative to adults, and that the expression of four genes through development
      correlated with estimated age. Compared to available data for mice, it appears
      that expression of some hearing genes is extended in juvenile bats. These results
      are consistent with a prolonged growth period required to develop larger cochlea
      relative to body size, a later maturation of high frequency hearing, and a
      greater dependence on high frequency hearing in echolocating bats.

PMID- 29073149
TI  - Intrapancreatic injection of human bone marrow-derived mesenchymal stem/stromal
      cells alleviates hyperglycemia and modulates the macrophage state in
      streptozotocin-induced type 1 diabetic mice.
AB  - Type 1 diabetes mellitus is a progressive disease caused by the destruction of
      pancreatic beta-cells, resulting in insulin dependency and hyperglycemia. While
      transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have
      been explored as an alternative therapeutic approach for diseases, the choice of
      delivery route may be a critical factor determining their sustainability. This
      study evaluated the effects of intrapancreatic and intravenous injection of human
      BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model.
      C57/BL6 mice were intraperitoneally injected with 115 mg/kg STZ on day 0. hBMMSCs
      (1 * 106 cells) or vehicle were injected into the pancreas or jugular vein on day
      7. Intrapancreatic, but not intravenous, hBMMSC injection significantly reduced
      blood glucose levels on day 28 compared with vehicle injection by the same route.
      This glucose-lowering effect was not induced by intrapancreatic injection of
      human fibroblasts as the xenograft control. Intrapancreatically injected
      fluorescence-labeled hBMMSCs were observed in the intra- and extra-lobular spaces
      of the pancreas, and intravenously injected cells were in the lung region,
      although the number of cells mostly decreased within 2 weeks of injection. For
      hBMMSCs injected twice into the pancreatic region on days 7 and 28, the injected
      mice had further reduced blood glucose to borderline diabetic levels on day 56.
      Animals injected with hBMMSCs twice exhibited increases in the plasma insulin
      level, number and size of islets, insulin-positive proportion of the total
      pancreas area, and intensity of insulin staining compared with vehicle-injected
      animals. We found a decrease of Iba1-positive cells in islets and an increase of
      CD206-positive cells in both the endocrine and exocrine pancreas. The hBMMSC
      injection also reduced the number of CD40-positive cells merged with glucagon
      immunoreactions in the islets. These results suggest that intrapancreatic
      injection may be a better delivery route of hBMMSCs for the treatment of type 1
      diabetes mellitus.

PMID- 29073151
TI  - Inhalation of volatile anesthetics via a laryngeal mask is associated with lower
      incidence of intraoperative awareness in non-critically ill patients.
AB  - BACKGROUND: Increased incidence of intraoperative awareness was reported in
      critically ill patients during major operations, particularly under total
      intravenous (TIVA) or endotracheal general anesthesia (ETGA). However, the
      incidence and effect of anesthesia techniques on awareness in generally healthy,
      non-critically ill patients during operations have yet to receive significant
      attention. METHODS AND RESULTS: This retrospective matched case-control study was
      conducted between January 2009 to December 2014. Surgical patients (ASA physical
      status I-III) whom reported intraoperative awareness during this study period
      were interviewed and their medical records were reviewed. The potential risk
      factors for awareness were compared with the non-case matched controls, who were
      randomly selected from the database. A total of 61436 patients were included and
      16 definite cases of intraoperative awareness were identified. Patients who
      received ETGA and TIVA had significantly higher incidence of developing awareness
      compared to those who were anesthetized using laryngeal masks (LMA) (P = 0.03).
      Compared with the matched controls (n = 80), longer anesthesia time was
      associated with increased incidence of awareness (odds ratio 2.04; 95% CI 1.30
      3.20, per hour increase). Perioperative use of muscle relaxant was also
      associated with increased incidence of awareness, while significantly lower
      incidence of awareness was found in patients who were anesthetized with volatile
      anesthetics. CONCLUSIONS: The overall incidence of awareness was 0.023% in the
      ASA<= III surgical patients who received general anesthesia. Anesthesia with a
      laryngeal mask under spontaneous ventilation and supplemented with volatile
      anesthetics may be the preferred anesthesia technique in generally healthy
      patients in order to provide a lower risk of intraoperative awareness.

PMID- 29073152
TI  - On the development of a semi-nonparametric generalized multinomial logit model
      for travel-related choices.
AB  - A semi-nonparametric generalized multinomial logit model, formulated using
      orthonormal Legendre polynomials to extend the standard Gumbel distribution, is
      presented in this paper. The resulting semi-nonparametric function can represent
      a probability density function for a large family of multimodal distributions.
      The model has a closed-form log-likelihood function that facilitates model
      estimation. The proposed method is applied to model commute mode choice among
      four alternatives (auto, transit, bicycle and walk) using travel behavior data
      from Argau, Switzerland. Comparisons between the multinomial logit model and the
      proposed semi-nonparametric model show that violations of the standard Gumbel
      distribution assumption lead to considerable inconsistency in parameter estimates
      and model inferences.

PMID- 29073150
TI  - L-arginine availability and arginase activity: Characterization of amino acid
      permease 3 in Leishmania amazonensis.
AB  - BACKGROUND: Leishmania uses the amino acid L-arginine as a substrate for
      arginase, enzyme that produces urea and ornithine, last precursor of polyamine
      pathway. This pathway is used by the parasite to replicate and it is essential to
      establish the infection in the mammalian host. L-arginine is not synthesized by
      the parasite, so its uptake occurs through the amino acid permease 3 (AAP3). AAP3
      is codified by two copies genes (5.1 and 4.7 copies), organized in tandem in the
      parasite genome. One copy presents the expression regulated by L-arginine
      availability. METHODOLOGY/PRINCIPAL FINDINGS: RNA-seq data revealed 14 amino acid
      transporters differentially expressed in the comparison of La-WT vs. La-arg-
      promastigotes and axenic amastigotes. The 5.1 and 4.7 aap3 transcripts were down
      regulated in La-WT promastigotes vs. axenic amastigotes, and in La-WT vs. La-arg-
      promastigotes. In contrast, transcripts of other transporters were up-regulated
      in the same comparisons. The amount of 5.1 and 4.7 aap3 mRNA of intracellular
      amastigotes was also determined in sample preparations from macrophages, obtained
      from BALB/c and C57BL/6 mice and the human THP-1 lineage infected with La-WT or
      La-arg-, revealing that the genetic host background is also important. We also
      determined the aap3 mRNA and AAP3 protein amounts of promastigotes and axenic
      amastigotes in different environmental growth conditions, varying pH, temperature
      and L-arginine availability. Interestingly, the increase of temperature increased
      the AAP3 level in plasma membrane and consequently the L-arginine uptake,
      independently of pH and L-arginine availability. In addition, we demonstrated
      that besides the plasma membrane localization, AAP3 was also localized in the
      glycosome of L. amazonensis promastigotes and axenic amastigotes.
      CONCLUSIONS/SIGNIFICANCE: In this report, we described the differential
      transcriptional profiling of amino acids transporters from La-WT and La-arg-
      promastigotes and axenic amastigotes. We also showed the increased AAP3 levels
      under amino acid starvation or its decrease in L-arginine supplementation. The
      differential AAP3 expression was determined in the differentiation of
      promastigotes to amastigotes conditions, as well as the detection of AAP3 in the
      plasma membrane reflecting in the L-arginine uptake. Our data suggest that
      depending on the amino acid pool and arginase activity, Leishmania senses and
      could use an alternative route for the amino acid transport in response to stress
      signaling.

PMID- 29073153
TI  - Thermosensitive hydrogels deliver bioactive protein to the vaginal wall.
AB  - The pathophysiology and natural history of pelvic organ prolapse (POP) are poorly
      understood. Consequently, our approaches to treatment of POP are limited.
      Alterations in the extracellular matrix components of pelvic support ligaments
      and vaginal tissue, including collagen and elastin, have been associated with the
      development of POP in animals and women. Prior studies have shown the protease
      MMP-9, a key player of ECM degradation, is upregulated in vaginal tissues from
      both mice and women with POP. On the other hand, fibulin-5, an elastogenic
      organizer, has been found to inhibit MMP-9 in the vaginal wall. Hence, we
      hypothesized that prolonged release of fibulin-5 may delay progression of POP. To
      test the hypothesis, oligo (ethylene glycol)-based thermosensitive hydrogels were
      fabricated, characterized and then used to deliver fibulin-5 to the vaginal wall
      and inhibit MMP-9 activity. The results indicate that hydrogels are cell and
      tissue compatible. The hydrogels also prolong the 1/2 life of fibulin-5 in
      cultured vaginal fibroblasts and in the vaginal wall in vivo. Finally, fibulin-5
      containing hydrogels resulted in incorporation of fibulin-5 into the vaginal
      matrix and inhibition of MMP-9 for several weeks after injection. These results
      support the idea of fibulin-5 releasing hydrogel being developed as a new
      treatment for POP.

PMID- 29073154
TI  - Cortical functional topography of high-frequency gamma activity relates to
      perceptual decision: an Intracranial study.
AB  - High-frequency activity (HFA) is believed to subserve a functional role in
      cognition, but these patterns are often not accessible to scalp EEG recordings.
      Intracranial studies provide a unique opportunity to link the all-encompassing
      range of high-frequency patterns with holistic perception. We tested whether the
      functional topography of HFAs (up to 250Hz) is related to perceptual decision
      making. Human intracortical data were recorded (6 subjects; >250channels) during
      an ambiguous object-recognition task. We found a spatial topography of HFAs
      reflecting processing anterior dorsal and ventral streams, linked to decision
      independently of the type of processed object/stimulus category. Three distinct
      regional fingerprints could be identified, with lower gamma frequency patterns
      (<45Hz) dominating in the anterior semantic ventral object processing and
      dorsoventral integrating networks and evolving later, during perceptual decision
      phases, than early sensory posterior patterns (60-250Hz). This suggests that
      accurate object recognition/perceptual decision-making is related to distinct
      spatiotemporal signatures in the low gamma frequency range.

PMID- 29073155
TI  - Genetic variability in LMP2 and LMP7 is associated with the risk of esophageal
      squamous cell carcinoma in the Kazakh population but is not associated with HPV
      infection.
AB  - The Kazakh population in Xinjiang Province in northwestern China exhibits a high
      incidence of esophageal squamous cell carcinoma (ESCC). Although the etiology of
      esophageal carcinoma (EC) has not been elucidated, there are reports of the
      involvement of an immunologic mechanism. In the current study, 268 Kazakh ESCC
      patients and 500 age- and sex-matched control subjects were recruited. DNA was
      extracted from paraffin-embedded tumor specimens from the patients and peripheral
      blood lymphocytes from the controls and used for LMP2/LMP7 genotyping. Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was
      performed to detect LMP2/LMP7 gene single-nucleotide polymorphisms (SNPs). We
      found a clear increased risk of ESCC in the Kazakh population for the
      heterozygous LMP2 R/C genotype and the homozygous C/C genotype (OR = 1.470, 95%CI
      = 1.076-2.008, p = 0.015 forLMP2R/C; OR = 2.048, 95% CI = 1.168-3.591, p = 0.011
      for LMP2 C/C). Conversely, the heterozygous LMP7 Q/K polymorphism was found to
      decrease the risk of ESCC in this population (OR = 0.421, 95% CI = 0.286-0.621, p
      = 8.83*10-6). Moreover, LMP2 R/C+C/C genotype was associated with increased tumor
      invasion depth (p = 0.041). Haplotype analysis showed that haplotype A, which
      includes wild-type homozygous LMP2/TAP1 and mutant LMP7, decreases susceptibility
      to ESCC in the Kazakh population; in contrast, haplotype E, which includes wild
      type homozygous LMP2/LMP7/TAP1, acts as a risk factor for increased
      susceptibility to ESCC. This is the first study to report that the heterozygous
      LMP2 R/C and homozygous C/C genotypes increase susceptibility to ESCC in the
      Kazakh population and that the heterozygous LMP7 Q/K genotype decreases
      susceptibility to ESCC in this population. Nevertheless, neither LMP2 nor LMP7
      was associated with human papillomavirus (HPV) infection. Understanding LMP2/LMP7
      genetic variability will provide a new therapeutic perspective for Kazakh
      patients with ESCC.

PMID- 29073157
TI  - Highly divergent 16S rRNA sequences in ribosomal operons of Scytonema hyalinum
      (Cyanobacteria).
AB  - A highly divergent 16S rRNA gene was found in one of the five ribosomal operons
      present in a species complex currently circumscribed as Scytonema hyalinum
      (Nostocales, Cyanobacteria) using clone libraries. If 16S rRNA sequence
      macroheterogeneity among ribosomal operons due to insertions, deletions or
      truncation is excluded, the sequence heterogeneity observed in S. hyalinum was
      the highest observed in any prokaryotic species thus far (7.3-9.0%). The
      secondary structure of the 16S rRNA molecules encoded by the two divergent
      operons was nearly identical, indicating possible functionality. The 23S rRNA
      gene was examined for a few strains in this complex, and it was also found to be
      highly divergent from the gene in Type 2 operons (8.7%), and likewise had nearly
      identical secondary structure between the Type 1 and Type 2 operons. Furthermore,
      the 16S-23S ITS showed marked differences consistent between operons among
      numerous strains. Both operons have promoter sequences that satisfy consensus
      requirements for functional prokaryotic transcription initiation. Horizontal gene
      transfer from another unknown heterocytous cyanobacterium is considered the most
      likely explanation for the origin of this molecule, but does not explain the
      ultimate origin of this sequence, which is very divergent from all 16S rRNA
      sequences found thus far in cyanobacteria. The divergent sequence is highly
      conserved among numerous strains of S. hyalinum, suggesting adaptive advantage
      and selective constraint of the divergent sequence.

PMID- 29073156
TI  - Comparison of clinical performance between trifocal and bifocal intraocular
      lenses: A meta-analysis.
AB  - PURPOSE: To compare the clinical performance between trifocal and bifocal
      intraocular lenses in bilateral cataract and/or refractive lens exchange (RLE)
      surgery. METHODS: A comprehensive literature search of PubMed, EMBASE, Cochrane
      Controlled Trials Register and Web of Science was performed through October 2016
      to identify randomized, controlled trials (RCTs) and comparative cohort studies.
      The primary outcomes were uncorrected distance visual acuity (UDVA), uncorrected
      intermediate visual acuity (UIVA), uncorrected near visual acuity (UNVA), defocus
      curve, spectacle independence, patient satisfaction and contrast sensitivity. The
      secondary outcomes were residual sphere, spherical equivalent (SE), cylinder and
      complications. RESULTS: Six RCTs and 2 cohort studies including 568 eyes (278 in
      the trifocal group and 290 in the bifocal group) were identified. There was a
      statically significant difference between the two groups in UDVA (WMD: -0.03, 95%
      CI: -0.05 to -0.01, P = 0.005), but the difference (0.03 log MAR) is not
      clinically significant. Intermediate visual acuity was better in the trifocal IOL
      group judging from UIVA and defocus curves. There was a statically significant
      difference between the two groups in residual cylinder (WMD: 0.11, 95% CI: 0.02
      to 0.20, P = 0.02), and subgroup AT Lisa tri 839MP trifocal also showed
      significant better UNVA than bifocal IOLs (WMD: -0.13, 95% CI: -0.17 to -0.08,
      P<0.00001). However, no significant differences were observed in UNVA (WMD: 
      0.04, 95% CI: -0.11 to 0.02, P = 0.19), spectacle independence (WMD: 1.27, 95%
      CI: 0.89 to 18.15, P = 0.07), patient satisfaction (WMD: 4.01, 95% CI: 0.07 to
      22.72, P = 0.87), residual sphere (WMD: -0.03, 95% CI: -0.18 to 0.13, P = 0.74),
      SE (WMD: 0.04, 95% CI: -0.09 to 0.16, P = 0.55) or complications (WMD: 2.08, 95%
      CI: 0.35 to 12.43, P = 0.42). CONCLUSIONS: Trifocal IOL technology (especially AT
      Lisa trifocal 839M trifocal) had a clear advantage over bifocal IOLs in
      intermediate visual acuity, while both trifocal IOLs and bifocal IOLs showed
      excellent performance in distance visual acuity. AT Lisa trifocal 839M trifocal
      could provide better uncorrected near visual acuity than bifocal IOLs. However,
      more evidence is needed to compare their spectacle independence, higher
      satisfaction rate, and photic phenomena.

PMID- 29073158
TI  - On the automaticity of relational stimulus processing: The (extrinsic) relational
      Simon task.
AB  - We introduce the (extrinsic) relational Simon task as a tool for capturing
      automatic relational stimulus processing. In three experiments, participants
      responded to a perceptual relation between two stimuli. Results showed that
      participants were faster and more accurate to respond when the (task-irrelevant)
      conceptual relation between these stimuli was compatible (rather than
      incompatible) with the (extrinsic) relational meaning of the required responses.
      This effect was replicated irrespective of the type of stimulus materials used,
      irrespective of the similarity between the relational information that was task
      relevant and the relational information that was task-irrelevant, and
      irrespective of the complexity of the task-irrelevant relational information. Our
      findings add to a growing body of evidence showing that relational stimulus
      processing can occur under conditions of automaticity.

PMID- 29073159
TI  - Body mass index influences infliximab post-infusion levels and correlates with
      prospective loss of response to the drug in a cohort of inflammatory bowel
      disease patients under maintenance therapy with Infliximab.
AB  - INTRODUCTION: Infliximab is an effective treatment for inflammatory bowel disease
      (IBD). Studies differ regarding the influence of body mass index (BMI) on the
      response to infliximab, with the majority of studies indicating that increased
      BMI may be associated with a poorer response to Infliximab. However, the
      pharmacokinetic mechanisms causing this have not yet been reported. AIMS: Examine
      the correlation between BMI/immunosuppressant use with clinical response, trough
      and post-infusion levels of infliximab, tumour necrosis factor-alpha(TNF-alpha)
      and anti-drug antibodies(ATI), and determine if these factors can predict future
      response. METHODS: We collected serum from 24 patients receiving Infliximab
      before and 30 minutes following infusion. Clinical parameters were collected
      retrospectively and prospectively. ELISA measurements of infliximab, TNF-alpha
      and ATI were performed. RESULTS: We confirmed that patients with higher
      infliximab trough levels have a better response rate and that patients with an
      elevated BMI display a higher rate of loss of response (20%). Patients with a
      higher BMI had elevated post-infusion levels of infliximab. Additionally, the
      ratio of IFX/TNF-alpha trough levels correlated with clinical response to the
      following infusion. CONCLUSION: This study confirms that an elevated BMI is
      associated with a poorer response to infliximab. For the first time, we describe
      that a higher BMI correlates with higher post-infusion levels, however this does
      not correlate with a higher rate of response to the drug, suggesting that
      circulating drug levels do not correlate with tissue levels. Furthermore, in our
      small cohort of patients, we identified a possible predictive marker of future
      response to treatment which may be used to guide dose escalation and predict non
      response to infliximab.

PMID- 29073161
TI  - Effectiveness of different types of hair traps for brown bear research and
      monitoring.
AB  - Non-invasive sampling by hair-trapping is increasingly used worldwide in wildlife
      research. Despite this rise and the potential of hair samples for ecology and
      conservation studies, the relative performance of hair collection devices has
      been rarely tested. Here, we compare the effectiveness of five types of hair
      traps for brown bears Ursus arctos in the Carpathian Mountains (SE Poland) and
      test the effects of trap type, season, number of days elapsed since trap
      installation and trap features on the trapping success in order to provide
      recommendations for optimal sampling in future studies. The trap types were
      corral, path-trap, "smola"(beechwood tar) tree-trap, turpentine tree-trap and
      natural rub. In 2010, we collected 858 hair samples during 2330 inspections of
      175 hair traps and found that the most effective traps were smola tree-traps
      (mean percentage of successful inspections +/- SD: 30.2% +/- 26.0) and natural
      rubs (50.8% +/- 16.7). Based on this finding, over the following 2 years we
      focused on 24 smola tree-traps and eight natural rubs. During this long-term
      survey (2010-2012, 969 inspections, 1322 samples collected) the trapping success
      increased with time and smola tree-traps achieved similar effectiveness to
      natural rubs (45.5% +/- 29.7 and 45.9 +/- 23.4, respectively). We show that when
      baiting smola tree-traps ten weeks prior to research or monitoring, sampling
      effectiveness can reach up to 30%. Taking into account the logistical and
      methodological constraints associated with detecting and using natural rubs for a
      proper survey design, we recommend using smola tree-traps baited in advance for
      hair sampling in wildlife studies.

PMID- 29073160
TI  - A novel FLNC frameshift and an OBSCN variant in a family with distal muscular
      dystrophy.
AB  - A novel FLNC c.5161delG (p.Gly1722ValfsTer61) mutation was identified in two
      members of a French family affected by distal myopathy and in one healthy
      relative. This FLNC c.5161delG mutation is one nucleotide away from a previously
      reported FLNC mutation (c.5160delC) that was identified in patients and in
      asymptomatic carriers of three Bulgarian families with distal muscular dystrophy,
      indicating a low penetrance of the FLNC frameshift mutations. Given these
      similarities, we believe that the two FLNC mutations alone can be causative of
      distal myopathy without full penetrance. Moreover, comparative analysis of the
      clinical manifestations indicates that patients of the French family show an
      earlier onset and a complete segregation of the disease. As a possible
      explanation of this, the two French patients also carry a OBSCN c.13330C>T
      (p.Arg4444Trp) mutation. The p.Arg4444Trp variant is localized within the OBSCN
      Ig59 domain that, together with Ig58, binds to the ZIg9/ZIg10 domains of titin at
      Z-disks. Structural and functional studies indicate that this OBSCN p.Arg4444Trp
      mutation decreases titin binding by ~15-fold. On this line, we suggest that the
      combination of the OBSCN p.Arg4444Trp variant and of the FLNC c.5161delG
      mutation, can cooperatively affect myofibril stability and increase the
      penetrance of muscular dystrophy in the French family.

PMID- 29073162
TI  - Category-specific neuronal activity in left and right auditory cortex and in
      medial geniculate body of monkeys.
AB  - We address the question of whether the auditory cortex of the left and right
      hemisphere and the auditory thalamus are differently involved in the performance
      of cognitive tasks. To understand these differences on the level of single
      neurons we compared neuronal firing in the primary and posterior auditory cortex
      of the two hemispheres and in the medial geniculate body in monkeys while
      subjects categorized pitch relationships in tone sequences. In contrast to
      earlier findings in imaging studies performed on humans, we found little
      difference between the three brain regions in terms of the category-specificity
      of their neuronal responses, of tonic firing related to task components, and of
      decision-related firing. The differences between the results in humans and
      monkeys may result from the type of neuronal activity considered and how it was
      analyzed, from the auditory cortical fields studied, or from fundamental
      differences between these species.

PMID- 29073163
TI  - The usefulness of appetite and energy intake-based algorithms to assess treatment
      effect of a bacterial infection: An observational prospective study.
AB  - BACKGROUND: The diagnosis of infectious diseases and the duration of antibiotic
      therapies are generally based on empirical rules. Studies implicate that the use
      biological markers can be used as a reliable method to shorten antibiotic
      therapies. The return of appetite is a clinical aspect of recovery from an
      infection that may be used to guide antibiotic therapies. OBJECTIVE: To compare
      changes in appetite and daily energy intake with changes in CRP-levels in
      patients recovering from an infection. DESIGN: Observational study using a
      consecutive sample of patients admitted to the unit for infectious diseases at a
      University Hospital in Sweden, February to April 2014. Energy intake, CRP-levels
      and appetite were recorded daily. Energy intake was calculated using estimated
      energy contents. Appetite was measured using a validated visual analogue scale.
      Changes in daily energy intakes, CRP-levels and appetite were analysed. RESULTS:
      49 patients (51% men) were included in the analysis from the overall population
      of 256 patients. During the length of the stay (median 3 days) CRP-levels fell in
      92% of the patients (p<0.001), daily energy intake increased in 73% (median
      intake +6381 kJ/day, p<0.001) and appetite increased in 55% of the patients (p =
      0.181). VAS-estimations of appetite augmented in 55%, decreased in 41% and were
      equal in 5% of the patients (p = 0.181). There was a non-significant difference
      in the within-subject variances in daily energy intake between female and male
      patients but not in other subsets. CONCLUSIONS: We found a significantly increase
      in the daily energy intake but not in self-estimated appetite in patients
      recovering from an infection. We suggest measuring the daily energy intake as a
      complement to other biological and clinical markers among inpatients to assess
      treatment effect.

PMID- 29073164
TI  - Transcriptome analysis of sheep oral mucosa response to Orf virus infection.
AB  - Contagious ecthyma is a highly contagious disease with worldwide distribution,
      which is caused by the Orf virus (ORFV) belonging to the Parapoxvirus. To study
      the alteration of host gene expression in response to ORFV infection at the
      transcriptional level, several young small-tailed Han sheep were inoculated with
      ORFV, and their oral mucosa tissue samples (T0, T3, T7 and T15) were collected on
      day 0, 3, 7 and 15 after ORFV infection respectively. RNA-seq transcriptome
      comparisons were performed, showing that 1928, 3219 and 2646 differentially
      expressed genes (DEGs) were identified among T3 vs. T0, T7 vs. T0, and T15 vs. T0
      respectively. Gene Ontology (GO) analyses of the DEGs from these comparisons,
      revealed that ORFV might provoke vigorous immune response of the host cells
      during the early stage of infection. Moreover, GO and network analysis showed
      that positive and negative regulative mechanisms of apoptosis were integrated in
      the host cells through up or down-regulating the expression level of DEGs
      involved in apoptotic pathways, in order to reach a homeostasis of oral mucosa
      tissues during the exposure to ORFV infection. In conclusion, our study for the
      first time describes the direct effects of ORFV on the global host gene
      expression of its host using high-throughput RNA sequencing, which provides a
      resource for future characterizing the interaction mechanism between the
      mammalian host and ORFV.

PMID- 29073165
TI  - Negative legacy of obesity.
AB  - Obesity promotes excessive inflammation, which is associated with senescence-like
      changes in visceral adipose tissue (VAT) and the development of type 2 diabetes
      (T2DM) and cardiovascular diseases. We have reported that a unique population of
      CD44hi CD62Llo CD4+ T cells that constitutively express PD-1 and CD153 exhibit
      cellular senescence and cause VAT inflammation by producing large amounts of
      osteopontin. Weight loss improves glycemic control and reduces cardiovascular
      disease risk factors, but its long-term effects on cardiovascular events and
      longevity in obese individuals with T2DM are somewhat disappointing and not well
      understood. High-fat diet (HFD)-fed obese mice were subjected to weight reduction
      through a switch to a control diet. They lost body weight and visceral fat mass,
      reaching the same levels as lean mice fed a control diet. However, the VAT of
      weight reduction mice exhibited denser infiltration of macrophages, which formed
      more crown-like structures compared to the VAT of obese mice kept on the HFD.
      Mechanistically, CD153+ PD-1+ CD4+ T cells are long-lived and not easily
      eliminated, even after weight reduction. Their continued presence maintains a
      self-sustaining chronic inflammatory loop via production of large amounts of
      osteopontin. Thus, we concluded that T-cell senescence is essentially a negative
      legacy effect of obesity.

PMID- 29073166
TI  - Bioremediation of cooking oil waste using lipases from wastes.
AB  - Cooking oil waste leads to well-known environmental impacts and its
      bioremediation by lipase-based enzymatic activity can minimize the high cytotoxic
      potential. In addition, they are among the biocatalysts most commercialized
      worldwide due to the versatility of reactions and substrates. However, although
      lipases are able to process cooking oil wastes, the products generated from this
      process do not necessarily become less toxic. Thus, the aim of the current study
      is to analyze the bioremediation of lipase-catalyzed cooking oil wastes, as well
      as their effect on the cytotoxicity of both the oil and its waste before and
      after enzymatic treatment. Thus, assessed the post-frying modification in soybean
      oil and in its waste, which was caused by hydrolysis reaction catalyzed by
      commercial and home-made lipases. The presence of lipases in the extracts
      obtained from orange wastes was identified by zymography. The profile of the
      fatty acid esters formed after these reactions was detected and quantified
      through gas chromatography and fatty acids profile compared through multivariate
      statistical analyses. Finally, the soybean oil and its waste, with and without
      enzymatic treatment, were assessed for toxicity in cytotoxicity assays conducted
      in vitro using fibroblast cell culture. The soybean oil wastes treated with core
      and frit lipases through transesterification reaction were less toxic than the
      untreated oils, thus confirming that cooking oil wastes can be bioremediated
      using orange lipases.

PMID- 29073167
TI  - Revealed willingness-to-pay versus standard cost-effectiveness thresholds:
      Evidence from the South African HIV Investment Case.
AB  - BACKGROUND: The use of cost-effectiveness thresholds based on a country's income
      per capita has been criticized for not being relevant to decision making, in
      particular in middle-income countries such as South Africa. The recent South
      African HIV Investment Case produced an alternative cost-effectiveness threshold
      for HIV prevention and treatment interventions based on estimates of life years
      saved and the country's committed HIV budget. METHODS: We analysed the optimal
      mix of HIV interventions over a baseline of the current HIV programme under the
      committed HIV budget for 2016-2018. We calculated the incremental cost
      effectiveness ratio (ICER) as cost per life-year saved (LYS) of 16 HIV prevention
      and treatment interventions over 20 years (2016-2035). We iteratively evaluated
      the most cost effective option (defined by an intervention and its coverage) over
      a rolling baseline to which the more cost effective options had already been
      added, thereby allowing for diminishing marginal returns to interventions. We
      constrained the list of interventions to those whose combined cost was affordable
      under the current HIV budget. Costs are presented from the government
      perspective, unadjusted for inflation and undiscounted, in 2016 USD. RESULTS: The
      current HIV budget of about $1.6 billion per year was sufficient to pay for the
      expansion of condom availability, medical male circumcision, universal treatment,
      and infant testing at 6 weeks to maximum coverage levels, while also implementing
      a social and behavior change mass media campaign with a message geared at
      increasing testing uptake and reducing the number of sexual partners. The
      combined ICER of this package of services was $547/ LYS. The ICER of the next
      intervention that was above the affordability threshold was $872/LYS.
      CONCLUSIONS: The results of the South African HIV Investment Case point to an HIV
      cost-effectiveness threshold based on affordability under the current budget of
      $547-872 per life year saved, a small fraction of the country's GDP per capita of
      about $6,000.

PMID- 29073170
TI  - Strain histograms are equal to strain ratios in predicting malignancy in breast
      tumours.
AB  - OBJECTIVES: To assess whether strain histograms are equal to strain ratios in
      predicting breast tumour malignancy and to see if either could be used to upgrade
      Breast Imaging Reporting and Data System (BI-RADS) 3 tumours for immediate
      biopsy. METHODS: Ninety-nine breast tumours were examined using B-mode BI-RADS
      scorings and strain elastography. Strain histograms and ratios were assessed, and
      areas- under-the-receiver-operating-characteristic-curve (AUROC) for each method
      calculated. In BI-RADS 3 tumours cut-offs for strain histogram and ratio values
      were calculated to see if some tumours could be upgraded for immediate biopsy.
      Linear regression was performed to evaluate the effect of tumour depth and size,
      and breast density on strain elastography. RESULTS: Forty-four of 99 (44.4%)
      tumours were malignant. AUROC of BI-RADS, strain histograms and strain ratios
      were 0.949, 0.830 and 0.794 respectively. There was no significant difference
      between AUROCs of strain histograms and strain ratios (P = 0.405), while they
      were both inferior to BI-RADS scoring (P<0.001, P = 0.008). Four out of 26 BI
      RADS 3 tumours were malignant. When cut-offs of 189 for strain histograms and
      1.44 for strain ratios were used to upgrade BI-RADS 3 tumours, AUROCS were 0.961
      (Strain histograms and BI-RADS) and 0.941 (Strain ratios and BI-RADS). None of
      them was significantly different from BI-RADS scoring alone (P = 0.249 and P =
      0.414). Tumour size and depth, and breast density influenced neither strain
      histograms (P = 0.196, P = 0.115 and P = 0.321) nor strain ratios (P = 0.411, P =
      0.596 and P = 0.321). CONCLUSION: Strain histogram analyses are reliable and easy
      to do in breast cancer diagnosis and perform comparably to strain ratio analyses.
      No significant difference in AUROCs between BI-RADS scoring and elastography
      combined with BI-RADS scoring was found in this study.

PMID- 29073168
TI  - Coronary endothelial function is better in healthy premenopausal women than in
      healthy older postmenopausal women and men.
AB  - BACKGROUND: Premenopausal women have fewer cardiovascular disease (CVD) events
      than postmenopausal women and age-matched men, but the reasons are not fully
      understood. Coronary endothelial function (CEF), a barometer of coronary vascular
      health, promises important insights into age and sex differences in
      atherosclerotic CVD risk, but has not been well characterized in healthy
      individuals because of the invasive nature of conventional CEF measurements.
      Recently developed magnetic resonance imaging (MRI) methods were used to quantify
      CEF (coronary area and flow changes in response to isometric handgrip exercise
      (IHE), an endothelial-dependent stressor) to test the hypothesis that healthy
      women have better CEF compared to men particularly at a younger age. METHODS: The
      study participants were 50 healthy women and men with no history of coronary
      artery disease (CAD) or traditional CV risk factors and Agatston coronary calcium
      score (on prior CT) <10 for those >= 50 years. Coronary cross-sectional area
      (CSA) measurements and flow-velocity encoded images (CBF) were obtained at
      baseline and during continuous IHE using 3T breath-hold cine MRI-IHE. CEF
      (%change in CSA and CBF with IHE) comparisons were made according to age and sex,
      and all women >=50 years were post-menopausal. RESULTS: In the overall
      population, there were no differences in CEF between men and women. However, when
      stratified by age and sex the mean changes in CSA and CBF during IHE were higher
      in younger premenopausal women than older postmenopausal women (%CSA: 15.2+/
      10.6% vs. 7.0+/-6.8%, p = 0.03 and %CBF: 59.0+/-37.0% vs. 30.5+/-24.5% p = 0.02).
      CBF change was also nearly two-fold better in premenopausal women than age
      matched men (59.0+/-37.0% vs. 33.6+/-12.3%, p = 0.03). CONCLUSIONS: Premenopausal
      women have nearly two-fold better mean CEF compared to postmenopausal women. CEF,
      measured by CBF change is also better in premenopausal women than age-matched men
      but there are no sex differences in CEF after menopause. Fundamental age and sex
      differences in CEF exist and may contribute to differences in the development and
      clinical manifestations of atherosclerotic CVD, and guide future trials targeting
      sex-specific mechanisms of atherogenesis.

PMID- 29073169
TI  - Expression and function of the miR-143/145 cluster in vitro and in vivo in human
      breast cancer.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that function as post
      transcriptional regulators of gene expression and are dysregulated in cancer.
      Studies of miRNAs to explore their potential as diagnostic and prognostic markers
      are of great scientific interest. Here, we investigate the functional properties
      and expression of the miR-143/145 cluster in breast cancer (BC) in vitro and in
      vivo. The ER positive MCF7, the HER2 positive SK-BR-3, and the triple negative
      cell line MDA-MB-231 were used to assess cell proliferation and cell invasion.
      Expression of miRNA in 108 breast cancers in the Norwegian Women and Cancer Study
      and 44 benign tissue controls were analyzed by microarray and validated by RT
      PCR. Further, in situ hybridization (ISH) was used to study the cellular and
      subcellular distribution of the miRNAs. In vitro, miR-143 promoted proliferation
      of MCF7 and MDA-MB-231 cells, whereas miR-145 and the cotransfection of both
      miRNAs inhibited proliferation in all three cell lines. The cells' invasive
      capacity was reduced after transfection and cotransfection of the miRNAs. In line
      with the tumor suppressive functions in vitro, the expression of miR-143 and miR
      145 was lower in malignant compared to benign breast tissue, and lower in the
      more aggressive tumors with higher tumor grade, loss of ER and the basal-like
      phenotype. ISH revealed miR-143 to be cytoplasmatic and predominantly expressed
      in luminal cells in benign tissue, whilst miR-145 was nuclear and with strong
      staining in myoepithelial cells. Both miRNAs were present in malignant epithelial
      cells and stromal fibroblasts in BC. This study demonstrates that miR-143 and 
      145 have functional properties and expression patterns typical for tumor
      suppressors, but the function is influenced by cellular factors such as cell type
      and miRNA cotransfection. Further, the nuclear functions of miR-145 should be
      explored for a more complete understanding of the complexity of miRNA regulation
      and function in BC.

PMID- 29073171
TI  - Transcriptome-wide analysis reveals the progress of Cordyceps militaris
      subculture degeneration.
AB  - BACKGROUND: The entomopathogenic mushroom Cordyceps militaris is an important
      medicinal and food resource owing to its various medicinal components and
      pharmacological effects. However, the high frequency of strain degeneration
      during subculture seriously restricts the large-scale production of C. militaris,
      and the mechanism underlying strain degeneration remains unclear. In this study,
      we artificially cultured C. militaris for six generations and compared changes
      during fruiting body growth. The transcriptome of six generations of C. militaris
      strains were sequenced with the Illumine Hiseq4000. RESULTS: The subcultured C.
      militaris strains degenerated beginning at the third generation, with incomplete
      fruiting body growth beginning at the fourth generation. Over 9,015 unigenes and
      731 new genes were identified. In addition, 35,323 alternative splicing (AS)
      events were detected in all samples, and more AS events occurred in the second,
      fourth and sixth generations. Compared with the first generation, the third
      generation (degenerated strain) included 2,498 differentially expressed genes
      (DEGs) including 1,729 up-regulated and 769 down-regulated genes. This number was
      higher than the number of DEGs in the second (1,892 DEGs), fourth (2,006 DEGs),
      fifth (2,273 DEGs) and sixth (2,188 DEGs) generations. Validation of RNA-seq by
      qRT-PCR showed that the expression patterns of 51 DEGs were in accordance with
      the transcriptome data. CONCLUSION: Our results suggest that the mechanism of C.
      militaris strain degeneration is associated with gene involved in toxin
      biosynthesis, energy metabolism, and DNA methylation and chromosome remodeling.

PMID- 29073172
TI  - Perceptions of gender equality, work environment, support and social issues for
      women doctors at a university hospital in Riyadh, Kingdom of Saudi Arabia.
AB  - The Kingdom of Saudi Arabia (KSA) is an Islamic monarchy and was established in
      1932. Saudi women first entered the medical field in 1975 and the country has
      since seen a steady increase in women pursuing medicine. However, there is
      limited data on gender related issues for women doctors practicing in Saudi
      Arabia. Therefore, our study objective was to assess the perception amongst peers
      regarding gender equality and social issues faced by women doctors in Saudi
      Arabia. An online anonymous cross-sectional survey was administered in English to
      doctors at King Khalid Hospital, affiliated to King Saud University, in Riyadh,
      between April and May of 2016. Of 1015 doctors, 304 (30%) participated, of which
      129 (42.4%) were females and 231 (76%) were Saudi nationals. The average age was
      32.4 years (+/-SD: 8.7). The majority opined that there was no gender
      discrimination in salaries (73.7% p-value = 0.4), hospital benefits (62.2% p
      value = 0.06) or entry into any field of Medicine/Pediatrics (68.4% p-value =
      0.207). However, only a minority believed that there was no gender discrimination
      for entry into surgery (37.3% p-value = .091). A higher proportion of male
      doctors agreed that promotion opportunities are equal (66.3% vs 45.7%, p-value =
      0.002). However, of 54 consultants, only 18 (33.3%) were women. Over half of the
      women (52.3%) reported that they never wear the face veil. Only a minority of
      male and female doctors (12.2%) believed women doctors should wear the veil since
      they examine male patients. Fewer respondents believed that female doctors face
      harassment from male doctors (14.5%) whereas 30.7% believed female doctors face
      harassment from male patients. More females, than males, agreed with the
      statement that female doctors are as committed to their careers as are males
      (92.2% vs 67.4%, p-value<0.0001). Of 304 participants, 210 (69.1%) said that they
      would still choose to become a doctor with approximately equal proportions
      between males and females (68% vs 70.5%, p-value = 0.79). In conclusion, our
      survey of male and female doctors at a government university hospital in Saudi
      Arabia revealed that the majority believed there was gender equality amongst
      doctors in terms of salaries, benefits, opportunities for promotion and entry
      into any field of medicine or pediatrics, but not surgery. However, there were
      significantly fewer women at consultant positions, a deficiency that needs to be
      addressed.

PMID- 29073174
TI  - Asthma is associated with atherosclerotic artery changes.
AB  - Asthma is a chronic airway inflammation with a potential systemic impact.
      Atherosclerosis is a chronic inflammatory artery disease. The aim of our study
      was to prove if there is a correlation between the occurrence of asthma and
      increased atherosclerotic vessel disorders. Vessel status was compared between
      mild-to-moderate, severe allergic asthma and matched controls. Measurements of
      artery stiffness were calculated by central pulse wave velocity, ultrasonographic
      strain imaging and ankle-brachial index. Atherosclerotic plaque burden was
      assessed by colour-coded duplex sonography. Additionally, analysis of
      cardiovascular and asthma blood markers was conducted. Arterial stiffness
      expressed as an increased central pulse wave velocity and decreased
      circumferential and radial strains as well as the prevalence of media sclerosis
      were significantly higher among asthma patients compared to controls.
      Atherosclerotic plaque burden was relevantly increased in asthma groups vs.
      controls (severe asthma: 43.1%, mild-to-moderate asthma: 25.0%, control: 14.3% of
      study participants). Except for the elevated IgE and fibrinogen concentrations as
      well as leukocyte number there were no relevant differences in the blood
      parameters between the groups. Allergic asthma is associated with distinct
      atherosclerotic artery changes compared to the respectively matched control
      collective. The severity of asthma correlates with more pronounced pathological
      vessel alternations.

PMID- 29073173
TI  - Notch activation is required for downregulation of HoxA3-dependent endothelial
      cell phenotype during blood formation.
AB  - Hemogenic endothelium (HE) undergoes endothelial-to-hematopoietic transition
      (EHT) to generate blood, a process that requires progressive down-regulation of
      endothelial genes and induction of hematopoietic ones. Previously, we have shown
      that the transcription factor HoxA3 prevents blood formation by inhibiting Runx1
      expression, maintaining endothelial gene expression and thus blocking EHT. In the
      present study, we show that HoxA3 also prevents blood formation by inhibiting
      Notch pathway. HoxA3 induced upregulation of Jag1 ligand in endothelial cells,
      which led to cis-inhibition of the Notch pathway, rendering the HE nonresponsive
      to Notch signals. While Notch activation alone was insufficient to promote blood
      formation in the presence of HoxA3, activation of Notch or downregulation of Jag1
      resulted in a loss of the endothelial phenotype which is a prerequisite for EHT.
      Taken together, these results demonstrate that Notch pathway activation is
      necessary to downregulate endothelial markers during EHT.

PMID- 29073175
TI  - Dissociation between behavior and motor cortical excitability before and during
      ballistic wrist flexion and extension in young and old adults.
AB  - PURPOSE: Aging is associated with slow reactive movement generation and poor
      termination. OBJECTIVE: We examined the hypothesis that the build-up of
      excitability in the primary motor cortex in the agonist muscle to generate
      ballistic wrist flexion and extension and in the antagonist to stop the movement,
      is lower and slower in old compared with young adults. METHODS: We measured the
      size of the motor potentials evoked (MEP) produced by transcranial magnetic
      stimulation (TMS), background integrated EMG (iEMG), and the MEP:iEMG ratio in
      healthy young (23 y, n = 14) and old adults' (73 y, n = 14) wrist flexors and
      extensors as they rapidly flexed or extended the wrist in response to an auditory
      cue. TMS was delivered at 80% of resting motor threshold randomly in 20 ms
      increments between 130 and 430 ms after the tone. RESULTS: Even though old
      compared to young adults executed the two wrist movements with ~23% longer
      movement duration and ~15% longer reaction time (both p < 0.05), the rise in
      MEP:iEMG ratio before the main similar in the two age groups. CONCLUSION: These
      data suggest that an adjustment of current models might be needed to better
      understand how and if age affects the build-up excitability accompanying movement
      generation and termination.

PMID- 29073176
TI  - A nested association mapping population identifies multiple small effect QTL
      conferring resistance against net blotch (Pyrenophora teres f. teres) in wild
      barley.
AB  - The net form of net blotch caused by the necrotrophic fungus Pyrenophora teres f.
      teres is a major disease of barley, causing high yield losses and reduced malting
      and feed quality. Exploiting the allelic richness of wild barley proved to be a
      valuable tool to broaden the genetic base of resistance of modern elite
      cultivars. In this study, a SNP-based nested association mapping (NAM) study was
      conducted to map QTL for P. teres resistance in the barley population HEB-25
      comprising 1,420 lines derived from BC1S3 generation. By scoring the percentage
      of infected leaf area followed by calculation of the average ordinate (AO) and
      scoring of the reaction type (RT) in two-year field trials a large variability of
      net blotch resistance across and within families of HEB-25 was observed. Genotype
      response to net blotch infection showed a range of 48.2% for AO (0.9-49.1%) and
      6.4 for RT (2.2-8.6). NAM based on 5,715 informative SNPs resulted in the
      identification of 24 QTL for resistance against net blotch. Out of these, six QTL
      are considered novel showing no correspondence to previously reported QTL for net
      blotch resistance. Overall, variation of net blotch resistance in HEB-25 turned
      out to be controlled by small effect QTL. Results indicate the presence of
      alleles in HEB-25 differing in their effect on net blotch resistance. Results
      provide valuable information regarding the genetic architecture of the complex
      barley-P. teres f. teres interaction as well as for the improvement of net blotch
      resistance of elite barley cultivars.

PMID- 29073177
TI  - Hypomethylated Fgf3 is a potential biomarker for early detection of oral cancer
      in mice treated with the tobacco carcinogen dibenzo[def,p]chrysene.
AB  - Genetic and epigenetic alterations observed at end stage OSCC formation could be
      considered as a consequence of cancer development and thus changes in normal or
      premalignant tissues which had been exposed to oral carcinogens such as
      Dibenzo[def,p]chrysene (DBP) may better serve as predictive biomarkers of disease
      development. Many types of DNA damage can induce epigenetic changes which can
      occur early and in the absence of evident morphological abnormalities. Therefore
      we used ERRBS to generate genome-scale, single-base resolution DNA methylomes
      from histologically normal oral tissues of mice treated with DBP under
      experimental conditions known to induce maximum DNA damage which is essential for
      the development of OSCC induced by DBP in mice. After genome-wide correction, 30
      and 48 differentially methylated sites (DMS) were identified between vehicle
      control and DBP treated mice using 25% and 10% differences in methylation,
      respectively. RT-PCR was further performed to examine the expressions of nine
      selected genes. Among them, Fgf3, a gene frequently amplified in head and neck
      cancer, showed most prominent and significant gene expression change (2.4*
      increases), despite the hypomethylation of Fgf3 was identified at >10kb upstream
      of transcription start site. No difference was observed in protein expression
      between normal oral tissues treated with DBP or vehicle as examined by
      immunohistochemistry. Collectively, our results indicate that Fgf3
      hypomethylation and gene overexpression, but not protein expression, occurred in
      the early stage of oral carcinogenesis induced by DBP. Thus, Fgf3 hypomethylation
      may serve as a potential biomarker for early detection of OSCC.

PMID- 29073178
TI  - Brominated indoles from a marine mollusc inhibit inflammation in a murine model
      of acute lung injury.
AB  - New drug leads for the treatment of inflammation are urgently needed. Marine
      molluscs are widely used as traditional medicines for the treatment of
      inflammation. Here we report the positive effects of a hypobranchial gland (HBG)
      extract and the dominant bioactive compound 6-bromoisatin from the Muricidae
      mollusc Dicathais orbita, for reducing lipopolysaccharide (LPS) induced acute
      lung inflammation in a mouse model. Both 6-bromoisatin and the HBG extract
      suppressed the inflammatory response in mice that were pre-treated by oral gavage
      at 48, 24 and 1 h prior to LPS infusion. The inflammatory antagonists were tested
      at concentrations of 0.5 mg/g and 0.1 mg/g HBG extract and 0.1 mg/g and 0.05 mg/g
      6-bromoisatin in carrier oil and all treatments reduced inflammation as indicated
      by a significant suppression of inflammatory markers present in bronchoalveolar
      lavage fluid (BALF), in comparison to LPS induced positive control mice
      administered the carrier oil alone (p < 0.0001). Tumour necrosis factor-alpha
      (TNFalpha) and interleukin-1 beta (IL-1beta) levels, in addition to total protein
      concentration were all significantly reduced in BALF from mice treated with the
      extract or 6-bromoisatin. Furthermore, all treatment groups showed significant
      reductions in neutrophil sequestration and preservation of the lung tissue
      architecture compared to the positive control (p < 0.0001). The combined results
      from this study and our previous in vitro studies indicate that 6-bromoisatin in
      the HGB extracts inhibit the activation of inflammatory signalling pathway. The
      results from this study further confirm that the HBG extract from Muricidae
      molluscs and 6-bromoisatin are bioavailable and effective in vivo, thus have
      potential for development as natural therapeutic agents for inflammation.

PMID- 29073179
TI  - Restitution characteristics of His bundle and working myocardium in isolated
      rabbit hearts.
AB  - The Purkinje system (PS) and the His bundle have been recently implicated as an
      important driver of the rapid activation rate after 1-2 minutes of ventricular
      fibrillation (VF). It is unknown whether activations during VF propagate through
      the His-Purkinje system to other portions of the the working myocardium (WM).
      Little is known about restitution characteristic differences between the His
      bundle and working myocardium at short cycle lengths. In this study, rabbit
      hearts (n = 9) were isolated, Langendorff-perfused, and electromechanically
      uncoupled with blebbistatin (10 MUM). Pacing pulses were delivered directly to
      the His bundle. By using standard glass microelectrodes, action potentials
      duration (APD) from the His bundle and WM were obtained simultaneously over a
      wide range of stimulation cycle lengths (CL). The global F-test indicated that
      the two restitution curves of the His bundle and the WM are statistically
      significantly different (P<0.05). Also, the APD of the His bundle was
      significantly shorter than that of WM throughout the whole pacing course
      (P<0.001). The CL at which alternans developed in the His bundle vs. the WM were
      shorter for the His bundle (134.2+/-13.1ms vs. 148.3+/-13.3ms, P<0.01) and 2:1
      block developed at a shorter CL in the His bundle than in WM (130.0+/-10.0 vs.
      145.6+/-14.2ms, P<0.01). The His bundle APD was significantly shorter than that
      of WM under both slow and rapid pacing rates, which suggest that there may be an
      excitable gap during VF and that the His bundle may conduct wavefronts from one
      bundle branch to the other at short cycle lengths and during VF.

PMID- 29073180
TI  - Risk factors for readmission in schizophrenia patients following involuntary
      admission.
AB  - BACKGROUND: Individuals with schizophrenia who are involuntarily admitted may
      have poorer prognosis, including higher readmission rates, than those voluntarily
      admitted. However, little is known about the risk factors for readmission in
      those schizophrenia patients who are involuntarily admitted. AIMS: We aim to
      explore the risk factors for readmission in this population. METHOD: We enrolled
      138 schizophrenia patients with involuntary admission from July 2008 to June 2013
      and followed those patients for readmission outcomes at 3 months and at 1 year.
      RESULTS: The one-year and 3-months readmission rates were 33.3% and 15.2%,
      respectively. Unmarried status (adjusted odds ratio (aOR) = 6.28, 95% CI: 1.48
      26.62), previous history of involuntary admission (aOR = 4.08, 95% CI: 1.19
      14.02), longer involuntary admission days (aOR = 1.04, 95% CI: 1.01-1.07) and
      shorter total admission days (aOR = 1.03, 95% CI: 1.01-1.05) were associated with
      increased risk for 1-year readmission. Younger age (aOR = 1.10, 95% CI 1.02-1.18)
      was associated with increased risk for 3-months readmission. CONCLUSIONS:
      Unmarried status, prior history of involuntary admission, longer involuntary
      admission days and shorter total admission days were associated with increased
      risk for 1-year readmission. Healthcare providers may need to focus on patients
      with these risk factors to reduce subsequent readmissions.

PMID- 29073181
TI  - Modulation of T-type Ca2+ channels by Lavender and Rosemary extracts.
AB  - Medicinal plants represent a significant reservoir of unexplored substances for
      early-stage drug discovery. Of interest, two flowering Mediterranean plants have
      been used for thousands of years for their beneficial effects on nervous
      disorders, including anxiety and mood. However, the therapeutic potential of
      these plants regarding their ability to target ion channels and neuronal
      excitability remains largely unknown. Towards this goal, we have investigated the
      ability of Lavender and Rosemary to modulate T-type calcium channels (TTCCs).
      TTCCs play important roles in neuronal excitability, neuroprotection, sensory
      processes and sleep. These channels are also involved in epilepsy and pain. Using
      the whole-cell patch-clamp technique, we have characterized how Lavender and
      Rosemary extracts, as well as their major active compounds Linalool and
      Rosmarinic acid, modulate the electrophysiological properties of recombinant
      TTCCs (CaV3.2) expressed in HEK-293T cells. Both the methanolic and essential oil
      extracts as well as the active compounds of these plants inhibit Cav3.2 current
      in a concentration-dependent manner. In addition, these products also induce a
      negative shift of the steady-state inactivation of CaV3.2 current with no change
      in the activation properties. Taken together, our findings reveal that TTCCs are
      a molecular target of the Lavender and Rosemary compounds, suggesting that
      inhibition of TTCCs could contribute to the anxiolytic and the neuroprotective
      effects of these plants.

PMID- 29073182
TI  - Blood parameters as biomarkers in a Salmonella spp. disease model of weaning
      piglets.
AB  - BACKGROUND: The weaning pig is used as an experimental model to assess the impact
      of diet on intestinal health. Blood parameters (BP) are considered a useful tool
      in humans, but there is very scarce information of such indicators in the weaning
      pig. The objective of the present study is to evaluate the use of different BP as
      indicators in an experimental model of salmonellosis. METHODOLOGY: Seventy-two 28
      day-old piglets were divided into four groups in a 2x2 factorial arrangement,
      with animals receiving or not a probiotic combination based on B. infantis IM1(r)
      and B. lactis BPL6 (109 colony forming units (cfu)/d) and orally challenged or
      not a week later with Salmonella Typhimurium (5x108 cfu). Blood samples of one
      animal per pen (N = 24) were taken four days post-inoculation for the evaluation
      of different BP using an I-stat(r) System and of plasmatic concentrations of
      zinc, iron and copper. PRINCIPAL FINDINGS: Results reported marginal deficiencies
      of zinc in piglets at weaning. Moreover, plasmatic zinc, copper and iron
      presented good correlations with weight gain (r 0.57, r -0.67, r 0.54
      respectively; P < 0.01). Blood electrolytes (Na+, Cl- and K+) decreased (P <
      0.01) only when the performance of the animals was seriously compromised and
      clinical symptoms were more apparent. Acid-base balance parameters such as HCO3-,
      TCO2 and BEecf significantly correlated with weight gain, but only in the
      challenged animals (r -0.54, r -0.55, and r -0.51, respectively; P < 0.05),
      suggesting metabolic acidosis depending on Salmonella infection. Glucose was
      affected by the challenge (P = 0.040), while Htc and Hgb increased with the
      challenge and decreased with the probiotic (P < 0.05). Furthermore, correlations
      of Glu, Htc and Hgb with weight gain were observed (P < 0.05). Overall, BP could
      be regarded as simple, useful indexes to assess performance and health of weaning
      piglets.

PMID- 29073184
TI  - Buccal dental-microwear and dietary ecology in a free-ranging population of
      mandrills (Mandrillus sphinx) from southern Gabon.
AB  - Analyses of dental micro- and macro-wear offer valuable information about dietary
      adaptations. The buccal surface of the teeth does not undergo attrition,
      indicating that dental microwear may directly inform about food properties. Only
      a few studies have, however, investigated the environmental and individual
      factors involved in the formation of such microwear in wild animals. Here, we
      examine variation of buccal microwear patterns of mandibular molars in a large
      free-ranging population of mandrills (Mandrillus sphinx). We first explore the
      influence of seasonality and individual's sex, age and tooth macrowear-expressed
      as the percent of dentine exposure (PDE)-on six microwear variables. Second, we
      analyze the interplay between individual's diet and PDE. In a last analysis, we
      revisit our results on mandrills in the light of other primate's microwear
      studies. We show that the average buccal scratch length and the frequency of
      vertical buccal scratches are both higher during the long dry season compared to
      the long rainy season, while we observe the inverse relationship for disto-mesial
      scratches. In addition, females present more disto-mesial scratches than males
      and older individuals present higher scratch density, a greater proportion of
      horizontal scratches but a lower proportion of vertical scratches than young
      animals. PDE yields similar results than individual's age confirming earlier
      results in this population on the relationship between age and tooth macrowear.
      Because seasonality and individual characteristics are both known to impact
      mandrills' diet in the study population, our results suggest that buccal
      microwear patterns may inform about individual feeding strategies. Furthermore,
      PDE increases with the consumption of potentially abrasive monocotyledonous
      plants, independently of the individuals' age, although it is not affected by
      food mechanical properties. Finally, buccal scratch densities by orientation
      appear as relevant proxies for discriminating between different primate taxa.

PMID- 29073183
TI  - Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein
      of respiratory syncytial virus.
AB  - Appropriate adjuvant selection may be essential to optimize the potency and to
      tailor the immune response of subunit vaccines. To induce protective responses
      against respiratory syncytial virus (RSV)-a highly prevalent childhood pathogen
      without a licensed vaccine-we previously engineered a pre-fusion-stabilized
      trimeric RSV F (pre-F) "DS-Cav1" immunogen, which induced high titer RSV
      neutralizing antibodies, in mice and non-human primates, when formulated with
      adjuvants Poly (I:C) and Poly (IC:LC), respectively. To assess the impact of
      different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and
      assessed immune responses. Very high RSV-neutralizing antibody responses (19,006
      EC50) were observed in naive mice immunized with 2 doses of DS-Cav1 adjuvanted
      with Sigma adjuvant system (SAS), an oil-in-water adjuvant, plus Carbopol; high
      responses (3658-7108) were observed with DS-Cav1 adjuvanted with Alum, SAS alone,
      Adjuplex, Poly (I:C) and Poly (IC:LC); and moderate responses (1251-2129) were
      observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or
      AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6). A
      balanced IgG1 and IgG2a (Th2/Th1) immune response was elicited in most of the
      high to very high response groups (all but Alum and Adjuplex). We also tested the
      immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1
      immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the
      response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5
      fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would
      enhanced the antibody response in DS-Cav1 immunized calves. While pre-F
      stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS
      plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune
      responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented
      by adjuvant, but the degree of adjuvant-induced enhancement appears to be both
      context-dependent and species-specific.

PMID- 29073185
TI  - Exploring the perceptions of physicians, caregivers and families towards
      artificial nutrition and hydration for people in permanent vegetative state: How
      can a photo-elicitation method help?
AB  - The question of withdrawing artificial nutrition and hydration from people in a
      permanent vegetative state sparks considerable ethical and legal debate.
      Therefore, understanding the elements that influence such a decision is crucial.
      However, exploring perceptions of artificial nutrition and hydration is
      methodologically challenging for several reasons. First, because of the emotional
      state of the professionals and family members, who are facing an extremely
      distressing situation; second, because this question mirrors representations
      linked to a deep-rooted fear of dying of hunger and thirst; and third, because of
      taboos surrounding death. We sought to determine the best method to explore such
      complex situations in depth. This article aims to assess the relevance of the
      photo-elicitation interview method to analyze the perceptions and attitudes of
      health professionals and families of people in a permanent vegetative state
      regarding artificial nutrition and hydration. The photo-elicitation interview
      method consists in inserting one or more photographs into a research interview.
      An original set of 60 photos was built using Google Images and participants were
      asked to choose photos (10 maximum) and talk about them. The situations of 32
      patients were explored in 23 dedicated centers for people in permanent vegetative
      state across France. In total, 138 interviews were conducted with health
      professionals and family members. We found that the photo-elicitation interview
      method 1) was well accepted by the participants and allowed them to express their
      emotions constructively, 2) fostered narration, reflexivity and introspection, 3)
      offered a sufficient "unusual angle" to allow participants to go beyond
      stereotypes and habits of thinking, and 4) can be replicated in other research
      areas. The use of visual methods currently constitutes an expanding area of
      research and this study stressed that this is of special interest to enhance
      research among populations facing end-of-life and ethical issues.

PMID- 29073188
TI  - Chemical crosslinking and mass spectrometry to elucidate the topology of integral
      membrane proteins.
AB  - Here we made an attempt to obtain partial structural information on the topology
      of multispan integral membrane proteins of yeast by isolating organellar
      membranes, removing peripheral membrane proteins at pH 11.5 and introducing
      chemical crosslinks between vicinal amino acids either using homo- or hetero
      bifunctional crosslinkers. Proteins were digested with specific proteases and the
      products analysed by mass spectrometry. Dedicated software tools were used
      together with filtering steps optimized to remove false positive crosslinks. In
      proteins of known structure, crosslinks were found only between loops residing on
      the same side of the membrane. As may be expected, crosslinks were mainly found
      in very abundant proteins. Our approach seems to hold to promise to yield low
      resolution topological information for naturally very abundant or strongly
      overexpressed proteins with relatively little effort. Here, we report novel XL-MS
      based topology data for 17 integral membrane proteins (Akr1p, Fks1p, Gas1p,
      Ggc1p, Gpt2p, Ifa38p, Ist2p, Lag1p, Pet9p, Pma1p, Por1p, Sct1p, Sec61p, Slc1p,
      Spf1p, Vph1p, Ybt1p).

PMID- 29073187
TI  - Sleep and cognitive performance of African-Americans and European-Americans
      before and during circadian misalignment produced by an abrupt 9-h delay in the
      sleep/wake schedule.
AB  - We conducted two studies of circadian misalignment in non-Hispanic African and
      European-Americans. In the first, the sleep/wake (light/dark) schedule was
      advanced 9 h, similar to flying east, and in the second these schedules were
      delayed 9 h, similar to flying west or sleeping during the day after night work.
      We confirmed that the free-running circadian period is shorter in African
      Americans compared to European-Americans, and found differences in the magnitude
      and direction of circadian rhythm phase shifts which were related to the
      circadian period. The sleep and cognitive performance data from the first study
      (published in this journal) documented the impairment in both ancestry groups due
      to this extreme circadian misalignment. African-Americans slept less and
      performed slightly worse during advanced/misaligned days than European-Americans.
      The current analysis is of sleep and cognitive performance from the second study.
      Participants were 23 African-Americans and 22 European-Americans (aged 18-44
      years). Following four baseline days (8 h time in bed, based on habitual sleep),
      the sleep/wake schedule was delayed by 9 h for three days. Sleep was monitored
      using actigraphy. During the last two baseline/aligned days and the first two
      delayed/misaligned days, beginning 2 h after waking, cognitive performance was
      assessed every 3 h using the Automated Neuropsychological Assessment Metrics
      (ANAM) battery. Mixed model ANOVAs assessed the effects of ancestry (African
      American or European-American) and condition (baseline/aligned or
      delayed/misaligned) on sleep and performance. There was decreased sleep and
      impaired cognitive performance in both ancestry groups during the two
      delayed/misaligned days relative to baseline/aligned days. Sleep and cognitive
      performance did not differ between African-Americans and European-Americans
      during either baseline/aligned or delayed/misaligned days. While our previous
      work showed that an advance in the sleep/wake schedule impaired the sleep of
      African-Americans more than European-Americans, delaying the sleep/wake schedule
      impaired the sleep and cognitive performance of African-Americans and European
      Americans equally.

PMID- 29073186
TI  - Ethical issues in the development and implementation of nutrition-related public
      health policies and interventions: A scoping review.
AB  - BACKGROUND: The limited integration of ethics in nutrition-related public health
      policies and interventions is one major concern for those who have the task of
      implementing them. Ethical challenges that are overlooked during the development
      of such interventions could raise serious ethical issues during their
      implementation and even after. As a result, these decision makers need technical
      support and ethical guidance for adaptation of interventions to local (cultural,
      social, economic, etc.) contexts. AIM: The goal of this scoping review is to
      delineate and "map" the range of ethical issues in nutrition-related public
      health interventions, as well as the range of the various fields in which they
      may arise. METHODS: A scoping review of empirical research and conceptual
      literature was conducted following the framework of Arksey and O'Malley. Searches
      using PubMed with Medical Subject Headings (MeSH) categories and Advanced Search
      Builder as well as in the Global Health Library were performed. The final sample
      consists of 169 publications. RESULTS: The ethics of public health prevention or
      treatment of obesity and non-communicable diseases is the most explicitly and
      frequently discussed subject. In comparison, ethical issues raised by public
      health interventions in the fields of undernutrition, breastfeeding,
      vitamin/mineral supplementation and food fortification, food security, food
      sustainability and food safety are addressed in a lower proportion of the sample.
      The results illustrate the various natures, types, and scopes of existing public
      health nutrition-related interventions, and the various ethical issues that may
      be raised by these interventions, in addition to the numerous and different
      contexts in which they may be implemented. DISCUSSION: The ethical issues faced
      in the development and implementation of nutrition-related public health
      interventions are varied and cannot be equated with, nor generalized about, when
      dealing with specific activities in this field. More importantly, these ethical
      issues cannot be managed without a careful consideration for the complexity of
      contexts in which nutrition-related interventions are expected to be implemented.
      These interventions engage a variety of actors with diverse perspectives and
      interests. We discuss these challenges and also comment on the importance of
      considering ethical impacts in the monitoring and evaluation of such
      interventions. CONCLUSION: General ethical frameworks or recommendations-although
      useful-cannot be expected to provide policy makers, implementators and other
      public health personnel with sufficient practical ethical guidance as they cannot
      consider and anticipate the particularities of all specific nutrition-related
      public health interventions and the complexity of the contexts in which they are
      implemented. Further research is needed in order to develop more targeted ethical
      frameworks.

PMID- 29073190
TI  - Effects of climate change on a mutualistic coastal species: Recovery from typhoon
      damages and risks of population erosion.
AB  - Presently, climate change has increased the frequency of extreme meteorological
      events such as tropical cyclones. In the western Pacific basin, these cyclones
      are called typhoons, and in this area, around Taiwan Island, their frequency has
      almost doubled since 2000. When approaching landmasses, typhoons have devastating
      effects on coastal vegetation. The increased frequency of these events has
      challenged the survival of coastal plant species and their posttyphoon recovery.
      In this study, a population of coastal gynodioecious Ficus pedunculosa var.
      mearnsii (Mearns fig) was surveyed for two years to investigate its recovery
      after Typhoon Morakot, which occurred in August 2009. Similar to all the Ficus
      species, the Mearns fig has an obligate mutualistic association with pollinating
      fig wasp species, which requires syconia (the closed Ficus inflorescence) to
      complete its life cycle. Moreover, male gynodioecious fig species produces both
      pollen and pollen vectors, whereas the female counterpart produces only seeds.
      The recovery of the Mearns fig was observed to be rapid, with the production of
      both leaves and syconia. The syconium:leaf ratio was greater for male trees than
      for female trees, indicating the importance of syconium production for the wasp
      survival. Pollinating wasps live for approximately 1 day; therefore, receptive
      syconia are crucial. Every typhoon season, few typhoons pass by the coasts where
      the Mearns fig grows, destroying all the leaves and syconia. In this paper, we
      highlight the potential diminution of the fig population that can lead to the
      extinction of the mutualistic pair of species. The effects of climate change on
      coastal species warrant wider surveys.

PMID- 29073189
TI  - Effect of erythropoietin administration on proteins participating in iron
      homeostasis in Tmprss6-mutated mask mice.
AB  - Tmprss6-mutated mask mice display iron deficiency anemia and high expression of
      hepcidin. The aim of the study was to determine the effect of erythropoietin
      administration on proteins participating in the control of iron homeostasis in
      the liver and spleen in C57BL/6 and mask mice. Administration of erythropoietin
      for four days at 50 IU/mouse/day increased hemoglobin and hematocrit in C57BL/6
      mice, no such increase was seen in mask mice. Erythropoietin administration
      decreased hepcidin expression in C57BL/6 mice, but not in mask mice.
      Erythropoietin treatment significantly increased the spleen size in both C57BL/6
      and mask mice. Furthermore, erythropoietin administration increased splenic
      Fam132b, Fam132a and Tfr2 mRNA content. At the protein level, erythropoietin
      increased the amount of splenic erythroferrone and transferrin receptor 2 both in
      C57BL/6 and mask mice. Splenic ferroportin content was decreased in
      erythropoietin-treated mask mice in comparison with erythropoietin-treated
      C57BL/6 mice. In mask mice, the amount of liver hemojuvelin was decreased in
      comparison with C57BL/6 mice. The pattern of hemojuvelin cleavage was different
      between C57BL/6 and mask mice: In both groups, a main hemojuvelin band was
      detected at approximately 52 kDa; in C57BL/6 mice, a minor cleaved band was seen
      at 47 kDa. In mask mice, the 47 kDa band was absent, but additional minor bands
      were detected at approximately 45 kDa and 48 kDa. The results provide support for
      the interaction between TMPRSS6 and hemojuvelin in vivo; they also suggest that
      hemojuvelin could be cleaved by another as yet unknown protease in the absence of
      functional TMPRSS6. The lack of effect of erythropoietin on hepcidin expression
      in mask mice can not be explained by changes in erythroferrone synthesis, as
      splenic erythroferrone content increased after erythropoietin administration in
      both C57BL/6 and mask mice.

PMID- 29073192
TI  - Lipid lowering therapy in patients with atherosclerotic cardiovascular diseases:
      Which matters in the real world? Statin intensity or low-density lipoprotein
      cholesterol level? - Data from a multicenter registry cohort study in Taiwan.
AB  - OBJECTIVE: Whether a low-density lipoprotein cholesterol (LDL-C) goal is
      essential in secondary prevention is still being debated. The aim of our study
      was to investigate whether achieving particular LDL-C level goals is associated
      with the reduction in the risk of major adverse cardiac events (MACEs) in
      patients with atherosclerotic cardiovascular diseases (ASCVD) on statin therapy.
      METHODS AND RESULTS: From January 2010 to August 2014, a total of 4099 patients
      with ASCVD in the Taiwan Secondary Prevention for patients with AtheRosCLErotic
      disease (T-SPARCLE) registry were analyzed. The risk of a MACE was lower in
      patients with LDL-C level under control at < 100 mg/dL by statins than in
      patients with LDL-C level >=100 mg/dL whether on statin therapy (hazard ratio
      [HR] 1.66, 95% confidence interval [CI] 1.04-2.63, p = 0.03) or not (HR 2.04, 95%
      CI 1.06-3.94, p = 0.03). In multivariate Cox model analyses, statin intensity had
      no significant predictive value, and LDL-C >= 100 mg/dL was associated with a
      slight but not significant trend toward increased risk of MACEs (HR 1.41, 95% CI
      0.96-2.07, p = 0.08). CONCLUSIONS: For patients with ASCVD on statin therapy
      guided by a target-driven strategy, failure to control LDL-C levels to < 100
      mg/dL was associated with higher risk of MACEs. Statin intensity alone had no
      significant impact on the risk of MACEs after multivariate adjustment.

PMID- 29073191
TI  - The effects of rhythm control strategies versus rate control strategies for
      atrial fibrillation and atrial flutter: A systematic review with meta-analysis
      and Trial Sequential Analysis.
AB  - BACKGROUND: Atrial fibrillation and atrial flutter may be managed by either a
      rhythm control strategy or a rate control strategy but the evidence on the
      clinical effects of these two intervention strategies is unclear. Our objective
      was to assess the beneficial and harmful effects of rhythm control strategies
      versus rate control strategies for atrial fibrillation and atrial flutter.
      METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, Web of Science, BIOSIS,
      Google Scholar, clinicaltrials.gov, TRIP, EU-CTR, Chi-CTR, and ICTRP for eligible
      trials comparing any rhythm control strategy with any rate control strategy in
      patients with atrial fibrillation or atrial flutter published before November
      2016. Our primary outcomes were all-cause mortality, serious adverse events, and
      quality of life. Our secondary outcomes were stroke and ejection fraction. We
      performed both random-effects and fixed-effect meta-analysis and chose the most
      conservative result as our primary result. We used Trial Sequential Analysis
      (TSA) to control for random errors. Statistical heterogeneity was assessed by
      visual inspection of forest plots and by calculating inconsistency (I2) for
      traditional meta-analyses and diversity (D2) for TSA. Sensitivity analyses and
      subgroup analyses were conducted to explore the reasons for substantial
      statistical heterogeneity. We assessed the risk of publication bias in meta
      analyses consisting of 10 trials or more with tests for funnel plot asymmetry. We
      used GRADE to assess the quality of the body of evidence. RESULTS: 25 randomized
      clinical trials (n = 9354 participants) were included, all of which were at high
      risk of bias. Meta-analysis showed that rhythm control strategies versus rate
      control strategies significantly increased the risk of a serious adverse event
      (risk ratio (RR), 1.10; 95% confidence interval (CI), 1.02 to 1.18; P = 0.02; I2
      = 12% (95% CI 0.00 to 0.32); 21 trials), but TSA did not confirm this result (TSA
      adjusted CI 0.99 to 1.22). The increased risk of a serious adverse event did not
      seem to be caused by any single component of the composite outcome. Meta-analysis
      showed that rhythm control strategies versus rate control strategies were
      associated with better SF-36 physical component score (mean difference (MD), 6.93
      points; 95% CI, 2.25 to 11.61; P = 0.004; I2 = 95% (95% CI 0.94 to 0.96); 8
      trials) and ejection fraction (MD, 4.20%; 95% CI, 0.54 to 7.87; P = 0.02; I2 =
      79% (95% CI 0.69 to 0.85); 7 trials), but TSA did not confirm these results. Both
      meta-analysis and TSA showed no significant differences on all-cause mortality,
      SF-36 mental component score, Minnesota Living with Heart Failure Questionnaire,
      and stroke. CONCLUSIONS: Rhythm control strategies compared with rate control
      strategies seem to significantly increase the risk of a serious adverse event in
      patients with atrial fibrillation. Based on current evidence, it seems that most
      patients with atrial fibrillation should be treated with a rate control strategy
      unless there are specific reasons (e.g., patients with unbearable symptoms due to
      atrial fibrillation or patients who are hemodynamically unstable due to atrial
      fibrillation) justifying a rhythm control strategy. More randomized trials at low
      risk of bias and low risk of random errors are needed. TRIAL REGISTRATION:
      PROSPERO CRD42016051433.

PMID- 29073193
TI  - Body-size structure of Central Iberian mammal fauna reveals semidesertic
      conditions during the middle Miocene Global Cooling Event.
AB  - We developed new quantitative palaeoclimatic inference models based on the body
      size structure of mammal faunas from the Old World tropics and applied them to
      the Somosaguas fossil site (middle Miocene, central Iberian Peninsula). Twenty
      six mammal species have been described at this site, including proboscideans,
      ungulates, carnivores, insectivores, lagomorphs and rodents. Our analyses were
      based on multivariate and bivariate regression models correlating climatic data
      and body-size structure of 63 modern mammal assemblages from Sub-Saharan Africa
      and the Indian subcontinent. The results showed an average temperature of the
      coldest month higher than 26 degrees C for the Somosaguas fossil site, a mean
      annual thermal amplitude around 10 degrees C, a drought length of 10 months, and
      an annual total precipitation greater than 200 mm per year, which are climate
      conditions typical of an ecotonal zone between the savanna and desert biomes.
      These results are congruent with the aridity peaks described over the middle
      Aragonian of Spain and particularly in the local biozone E, which includes
      Somosaguas. The aridity increase detected in this biozone is associated with the
      Middle Miocene Global Cooling Event. The environment of Somosaguas around 14 Ma
      was similar to the current environment in the Sahel region of North Africa, the
      Horn of Africa, the boundary area between the Kalahari and the Namib in Southern
      Africa, south-central Arabia, or eastern Pakistan and northwestern India. The
      distribution of modern vegetation in these regions follows a complex mosaic of
      plant communities, dominated by scattered xerophilous shrublands, semidesert
      grasslands, and vegetation linked to seasonal watercourses and ponds.

PMID- 29073195
TI  - Comparison of multistate Markov modeling with contemporary outcomes in a
      reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke
      treatment trial.
AB  - Historically, ordinal measures of functional outcome have been dichotomized for
      the primary analysis in acute stroke therapy trials. A number of alternative
      methods to analyze the ordinal scales have been proposed, with an emphasis on
      maintaining the ordinal structure as much as possible. In addition, despite the
      availability of longitudinal outcome data in many trials, the primary analysis
      consists of a single endpoint. Inclusion of information about the course of
      disease progression allows for a more complete understanding of the treatment
      effect. Multistate Markov modeling, which allows for the full ordinal scale to be
      analyzed longitudinally, is compared with previously suggested analytic
      techniques for the ordinal modified Rankin Scale (dichotomous-logistic
      regression; continuous-linear regression; ordinal- shift analysis, proportional
      odds model, partial proportional odds model, adjacent categories logit model;
      sliding dichotomy; utility weights; repeated measures). In addition, a multistate
      Markov model utilizing an estimate of the unobservable baseline outcome derived
      from principal component analysis is compared Each of the methods is used to re
      analyze the National Institute of Neurological Diseases and Stroke tissue
      plasminogen activator study which showed a consistently significant effect of
      tissue plasminogen activator using a global test of four dichotomized outcomes in
      the analysis of the primary outcome at 90 days post-stroke in the primary
      analysis. All methods detected a statistically significant treatment effect
      except the multistate Markov model without predicted baseline (p = 0.053). This
      provides support for the use of the estimated baseline in the multistate Markov
      model since the treatment effect is able to be detected with its inclusion.
      Multistate Markov modeling allows for a more refined examination of treatment
      effect and describes the movement between modified Rankin Scale states over time
      which may provide more clinical insight into the treatment effect. Multistate
      Markov models are feasible and desirable in describing treatment effect in acute
      stroke therapy trials.

PMID- 29073194
TI  - Change in the immune function of porcine iliac artery endothelial cells infected
      with porcine circovirus type 2 and its inhibition on monocyte derived dendritic
      cells maturation.
AB  - Porcine circovirus-associated disease is caused by porcine circovirus type 2
      (PCV2) infection, which targets iliac artery endothelial cells (PIECs); it leads
      to severe immunopathologies and is associated with major economic losses in the
      porcine industry. Here, we report that in vitro PCV2 infection of PIECs causes
      cell injury, which affects DC function as well as adaptive immunity.
      Specifically, PCV2 infection downregulated PIEC antigen-presenting molecule
      expression, upregulated cytokines involved in the immune and inflammatory
      response causing cell damage and repair, and altered the migratory capacity of
      PIECs. In addition, PCV2-infected PIECs inhibited DC maturation, enhanced the
      endocytic ability of DCs, and weakened the stimulatory effect of DCs on T
      lymphocytes. Together, these findings indicate that profound functional
      impairment of DCs in the presence of PCV2-infected PIECs may be a potential
      pathogenic mechanism associated with PCV2-induced porcine disease.

PMID- 29073196
TI  - FGF23 expression in rodents is directly induced via erythropoietin after
      inhibition of hypoxia inducible factor proline hydroxylase.
AB  - Plasma levels of FGF23 are increased in patients with chronic kidney disease.
      Beside its role in phosphate homeostasis, iron deficiency and anemia are
      associated with increased FGF23 plasma levels. Recently, FGF23 plasma levels were
      shown to be increased in mice after treatment with hypoxia inducible factor
      proline hydroxylase (HIF-PH) inhibitors which are strong inducers of
      erythropoietin and erythropoiesis and are known to modulate iron uptake and
      availability. Therefore we investigated a potential context between expression of
      FGF23 and stimulation of erythropoiesis using a HIF-PH inhibitor and
      erythropoietin in rats. FGF23 plasma levels are induced at peak levels 2 h after
      intravenous injection of recombinant human Erythropoietin (rhEPO). Likewise
      induction of endogenous EPO using a HIF-PH inhibitor (BAY 85-3934) is followed by
      an increase of FGF23 plasma levels. In contrast to rhEPO the HIF-PH inhibitor
      induces lower peak levels of FGF23 applying equivalent hematopoietic doses. Bone
      and bone marrow were identified as sources of EPO-induced FGF23. Immediate
      induction of FGF23 mRNA was also detected in EPO receptor positive murine
      hematopoietic BAF3 cells after treatment with rhEPO but not after treatment with
      the HIF-PH inhibitor. Pretreatment of mice with a neutralizing anti-EPO antibody
      abrogated FGF23 induction by the HIF-PH inhibitor. Thus, direct impact on FGF23
      expression by HIF-PH inhibition in vivo via hypoxia mimicking and modulation of
      iron metabolism appears unlikely. Collectively, the findings point to an EPO
      dependent regulation pathway of FGF23 gene expression which might be important in
      the context of erythropoiesis stimulating therapies in patients with renal
      anemia.

PMID- 29073197
TI  - Etiology and mode of presentation of chronic liver diseases in India: A multi
      centric study.
AB  - There is a paucity of health policy relevant data for chronic liver disease from
      India, impeding formulation of an interventional strategy to address the issue. A
      prospective, multicentric study to delineate the etiology and clinical profile of
      chronic liver disease in India is reported here. A centrally coordinated and
      monitored web-based data repository was developed (Feb, 2010 to Jan, 2013) and
      analyzed. Eleven hospitals from different parts of India participated. Data were
      uploaded into a web based proforma and monitored by a single centre according to
      a standardized protocol. 1.28% (n = 266621) of all patients (n = 20701383)
      attending the eleven participating hospitals of India had liver disease. 65807
      (24.68%) were diagnosed for the first time (new cases). Of these, 13014 (19.77%,
      median age 43 years, 73% males) cases of chronic liver disease were finally
      analyzed. 33.9% presented with decompensated cirrhosis. Alcoholism (34.3% of
      4413) was the commonest cause of cirrhosis while Hepatitis B (33.3%) was
      predominant cause of chronic liver disease in general and non-cirrhotic chronic
      liver disease (40.8% out of 8163). There was significant interregional
      differences (hepatitis C in North, hepatitis B in East and South, alcohol in
      North-east, Non-alcoholic Fatty Liver Disease in West) in the predominant cause
      of chronic liver disease. Hepatitis B (46.8% of 438 cases) was the commonest
      cause of hepatocellular Cancer.11.7% had diabetes. Observations of our study will
      help guide a contextually relevant liver care policy for India and could serve as
      a framework for similar endeavor in other developing countries as well.

PMID- 29073198
TI  - Gender-specific association of metabolic syndrome and its components with
      arterial stiffness in the general Chinese population.
AB  - OBJECTIVES: Metabolic syndrome (MS) is considered to be a cluster of interrelated
      risk factors for metabolism, which may increase arterial stiffness and
      cardiovascular morbidity. The cardio-ankle vascular index (CAVI) is a reliable
      indicator of arterial stiffness and early arteriosclerosis. The main objective of
      this study is to evaluate the gender-specific relationship between MS and CAVI in
      the general Chinese population. METHODS: A total of 1,301 subjects aged 20 to 60
      years participated in this study. CAVI was measured noninvasively using a Vasera
      VS-1000 device. Blood samples and waist circumference were examined to identify
      metabolic syndrome according to the criteria set forth in the 2009 Joint
      Scientific Statement. RESULTS: The prevalence of MS in the study subjects was
      17.4% (30.7% in males and 7.0% in females, P < 0.001). CAVI values were
      significantly higher in MS subjects than in non-MS subjects and increased
      linearly as the number of MS components increased in females, but not in males.
      Using multiple regression analysis, we found that BMI was correlated with CAVI in
      the overall population and in both genders, and that high-density lipoprotein
      cholesterol (HDL-C) was associated with CAVI in males, while the number of MS
      components was related to CAVI in females. CAVI values increased linearly with
      age in both genders (P-trend < 0.001 for both), and this correlation was stronger
      in males than in females. CONCLUSIONS: There are gender-specific differences in
      the association of MS and CAVI. First, the effects of the number of MS components
      on CAVI are stronger in females than in males. Second, the effect of each MS
      component on arterial stiffness may differ in relation to gender. In addition,
      aging affects arterial stiffness more severely in males, and the increase in
      arterial stiffness tends to occur at a younger age in males than in females.
      Larger samples and longitudinal studies are needed to further confirm our results
      in the future.

PMID- 29073199
TI  - Reduced expression of IQGAP2 and higher expression of IQGAP3 correlates with poor
      prognosis in cancers.
AB  - IQGAPs is a family of proteins which comprises three members, in humans. The
      expression pattern and role of IQGAP1 has been well established in many cancers,
      whereas those of IQGAP2 and IQGAP3, have mostly remained unexplored. We used
      available large datasets, to explore the pan-cancer status of these two genes in
      silico. Here we have analysed their mRNA expression and correlation with
      survivability in eight different cancers, including lung, breast, gastric, brain,
      colorectal, prostate, liver and kidney cancers and, their subtypes. The mRNA
      expression of IQGAP2 and IQGAP3 in individual cancers were analysed in two
      different publicly available databases viz. Oncomine and TCGA. The prognostic
      value of these genes in lung, breast and gastric cancer was analysed using Kaplan
      Meier Plotter database, whereas for brain, colorectal, liver, prostate and kidney
      cancers, SurvExpress database was used. These results were validated by
      immunohistochemistry in cancer tissues (stomach, prostate, brain, colorectal).
      Moreover, we did IQGAP2 and IQGAP3 genomic alteration and, promoter methylation
      analysis using cBioportal and Wanderer web tool, respectively. Most of the cancer
      types (lung, breast, prostate, brain, gastric, liver, kidney and colorectal)
      showed increased IQGAP3 mRNA expression. In contrast, the IQGAP2 transcript
      levels were reduced across different cancers viz. lung, breast, gastric, liver,
      kidney and colorectal cancer. IQGAP2 expression correlated positively with
      survivability, on the contrary, IQGAP3 expression levels correlated inversely
      with survivability, in most of the cancers. Collectively, enhanced IQGAP3 and
      reduced IQGAP2 levels were frequently observed in multiple cancers with the
      former predicting poor survivability and the later opposite. Methylation pattern
      was significantly altered in most of the cancer types. We found copy no.
      variation and mutations in specific cancers, for IQGAP2 and IQGAP3. Our in-vivo
      (IHC) data confirmed the in-silico findings completely. Hence, IQGAP2 and IQGAP3
      have potential to be used as prognostic markers or therapeutic targets in
      specific cancers.

PMID- 29073200
TI  - Torsional phacoemulsification: A pilot study to revise the "harm scale"
      evaluating the endothelial damage and the visual acuity after cataract surgery.
AB  - PURPOSE: To study the effect of torsional phacoemulsification energy on corneal
      endothelium evaluating the relationship between changes of endothelial cells and
      postoperative visual acuity. METHODS: This prospective clinical observational
      cohort study included 50 patients with cataract who underwent torsional
      phacoemulsification. Sequential quantitative and qualitative morphometric
      endothelial cell analyses of the cornea were performed four weeks preoperatively
      and six weeks postoperatively using noncontact specular microscopy. RESULTS: This
      work confirmed the strong relationship, described by a linear model (one-way
      ANOVA, R2 = 77.9%, P < 0.0001), between the percentage of endothelial cell loss
      (ECL%) and the 5-score harm scale. According to the Tukey post-hoc pairwise
      comparison test, distinct values of ECL% are grouped in 3 subsets. The value of
      ECL = 10% has been identified as cut-off to discriminate patients with excellent
      postoperative best-corrected visual acuity (BCVA > 85 letters) from those with
      just a good/satisfied visual outcome (BCVA <= 85 letters). Within the 5-score
      harm scale, there was a significant correlation among phaco energy
      intraoperatively delivered and the average endothelial cell loss. CONCLUSIONS:
      This study confirms the validity of the 5-score harm scale first proposed by
      Sorrentino and colleagues in 2016. This time, the method categorizes cataracts
      taking into account nucleus hardness and phaco cumulative dissipated energy.
      Predicting the harm on corneal endothelium, we can discriminate patients with
      excellent BCVA and with just good/satisfied BCVA. With torsional
      phacoemulsification with respect to longitudinal, the percentage of patients who
      can reach excellent BCVA is remarkably increased.

PMID- 29073201
TI  - Prediction of drug cocktail effects when the number of measurements is limited.
AB  - Cocktails of drugs can be more effective than single drugs, because they can
      potentially work at lower doses and avoid resistance. However, it is impossible
      to test all drug cocktails drawn from a large set of drugs because of the huge
      number of combinations. To overcome this combinatorial explosion problem, one can
      sample a relatively small number of combinations and use a model to predict the
      rest. Recently, Zimmer and Katzir et al. presented a model that accurately
      predicted the effects of cocktails at all doses based on measuring pairs of
      drugs. This model requires measuring each pair at several different doses and
      uses interpolation to reduce experimental noise. However, often, it is not
      possible to measure each pair at multiple doses (for example, in scarce patient
      derived tumor material or in large screens). Here, we ask whether measurements at
      only a single dose can also predict high-order drug cocktails. To address this,
      we present a fully factorial experimental dataset on all drug cocktails built of
      6 chemotherapy drugs on 2 cancer cell lines. We develop a formula that uses only
      pair measurements at a single dose to predict much of the variation up to 6-drug
      cocktails in the present data, outperforming commonly used Bliss independence and
      regression approaches. This model, called the pairs model, is an extension of the
      Bliss independence model to pairs: For M drugs, it equals the product of all pair
      effects to the power 1/(M-1). The pairs model also shows good agreement with
      previously published data on antibiotic triplets and quadruplets. The present
      model can only predict combinations at the same doses in which the pairs were
      measured and is not able to predict effects at other doses. This study indicates
      that pair-based approaches might be able to usefully predict and prioritize high
      order combinations, even in large screens or when material for testing is
      limited.

PMID- 29073202
TI  - Questionnaire survey of the pan-African trade in lion body parts.
AB  - The African lion is in decline across its range, and consumptive utilisation and
      trade of their body parts and skins has been postulated as a cause for concern.
      We undertook a pan-African questionnaire and literature survey to document
      informed opinion and evidence for the occurrence of domestic and international
      trade and consumption in African lion body parts across current and former range
      states. Sixty-five people from 18 countries participated in the online
      questionnaire survey (run from July 2014 to May 2015), with information provided
      for 28 countries (including 20 out of 24 countries believed to have extant
      populations). Respondents were experts within their professional spheres, and 77%
      had >=6 years relevant experience within lion conservation or allied wildlife
      matters. Their opinions revealed wide sub-regional differences in consumptive
      use, drivers of trade, and access to lions that impact wild lion populations in
      different ways. Traditional medicine practices (African and Asian) were perceived
      to be the main uses to which lion body parts and bones are put domestically and
      traded internationally, and there is reason for concern about persistent imports
      from former lion range states (mainly in West Africa) for parts for this purpose.
      The domestic, rather than international, trade in lion body parts was perceived
      to be a bigger threat to wild lion populations. Parts such as skin, claws, teeth
      and bones are thought to be in most demand across the continent. The impact of
      international trade on wild populations was acknowledged to be largely unknown,
      but occasionally was judged to be 'high', and therefore vigilance is needed to
      monitor emerging detrimental impacts. Seventeen countries were nominated as
      priorities for immediate monitoring, including: South Africa, Tanzania, Zimbabwe,
      Mozambique, Zambia, Botswana, Kenya, Nigeria, and Cameroon. Reasons for their
      selection include: prevalence of trophy hunting, 'hot spots' for poaching, active
      domestic trade in lion body parts, trade in curios for the tourist market, and
      histories of legal-illegal wildlife trade. This survey, and increased incident
      reports since mid-2015 of lion poisoning and poaching in Mozambique, Zimbabwe and
      South Africa, and sporadic poaching events in Uganda and Tanzania, are signalling
      an escalating trend in the trade of lion products that is an increasing threat to
      some national populations. The evidence is sufficient to make more detailed
      investigation of this trade a conservation priority.

PMID- 29073204
TI  - Non-linear pressure/temperature-dependence of high pressure thermal inactivation
      of proteolytic Clostridium botulinum type B in foods.
AB  - The effect of high pressure thermal (HPT) processing on the inactivation of
      spores of proteolytic type B Clostridium botulinum TMW 2.357 in four differently
      composed low-acid foods (green peas with ham, steamed sole, vegetable soup,
      braised veal) was studied in an industrially feasible pressure range and
      temperatures between 100 and 120 degrees C. Inactivation curves exhibited rapid
      inactivation during compression and decompression followed by strong tailing
      effects. The highest inactivation (approx. 6-log cycle reduction) was obtained in
      braised veal at 600 MPa and 110 degrees C after 300 s pressure-holding time. In
      general, inactivation curves exhibited similar negative exponential shapes, but
      maximum achievable inactivation levels were lower in foods with higher fat
      contents. At high treatment temperatures, spore inactivation was more effective
      at lower pressure levels (300 vs. 600 MPa), which indicates a non-linear
      pressure/temperature-dependence of the HPT spore inactivation efficiency. A
      comparison of spore inactivation levels achievable using HPT treatments versus a
      conventional heat sterilization treatment (121.1 degrees C, 3 min) illustrates
      the potential of combining high pressures and temperatures to replace
      conventional retorting with the possibility to reduce the process temperature or
      shorten the processing time. Finally, experiments using varying spore inoculation
      levels suggested the presence of a resistant fraction comprising approximately
      0.01% of a spore population as reason for the pronounced tailing effects in
      survivor curves. The loss of the high resistance properties upon cultivation
      indicates that those differences develop during sporulation and are not linked to
      permanent modifications at the genetic level.

PMID- 29073203
TI  - Dynamics and heterogeneity of brain damage in multiple sclerosis.
AB  - Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and
      degenerative processes that damage the central nervous system (CNS). However, it
      is not well understood how these events interact and evolve to evoke such a
      highly dynamic and heterogeneous disease. We established a hypothesis whereby the
      variability in the course of MS is driven by the very same pathogenic mechanisms
      responsible for the disease, the autoimmune attack on the CNS that leads to
      chronic inflammation, neuroaxonal degeneration and remyelination. We propose that
      each of these processes acts more or less severely and at different times in each
      of the clinical subgroups. To test this hypothesis, we developed a mathematical
      model that was constrained by experimental data (the expanded disability status
      scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66
      MS patients with a long-term follow-up (up to 20 years). Moreover, we validated
      this model in a second prospective cohort of 120 MS patients with a three-year
      follow-up, for which EDSS data and brain volume time series were available. The
      clinical heterogeneity in the datasets was reduced by grouping the EDSS time
      series using an unsupervised clustering analysis. We found that by adjusting
      certain parameters, albeit within their biological range, the mathematical model
      reproduced the different disease courses, supporting the dynamic CNS damage
      hypothesis to explain MS heterogeneity. Our analysis suggests that the
      irreversible axon degeneration produced in the early stages of progressive MS is
      mainly due to the higher rate of myelinated axon degeneration, coupled to the
      lower capacity for remyelination. However, and in agreement with recent
      pathological studies, degeneration of chronically demyelinated axons is not a key
      feature that distinguishes this phenotype. Moreover, the model reveals that lower
      rates of axon degeneration and more rapid remyelination make relapsing MS more
      resilient than the progressive subtype. Therefore, our results support the
      hypothesis of a common pathogenesis for the different MS subtypes, even in the
      presence of genetic and environmental heterogeneity. Hence, MS can be considered
      as a single disease in which specific dynamics can provoke a variety of clinical
      outcomes in different patient groups. These results have important implications
      for the design of therapeutic interventions for MS at different stages of the
      disease.

PMID- 29073205
TI  - McWRI1, a transcription factor of the AP2/SHEN family, regulates the biosynthesis
      of the cuticular waxes on the apple fruit surface under low temperature.
AB  - Cuticular waxes of plant and organ surfaces play an important role in protecting
      plants from biotic and abiotic stress and extending the freshness, storage time
      and shelf life in the post-harvest agricultural products. WRI1, a transcription
      factor of AP2/SHEN families, had been found to trigger the related genes taking
      part in the biosynthesis of seed oil in many plants. But whether WRI1 is involved
      in the biosynthesis of the cuticular waxes on the Malus fruits surface has been
      unclear. We investigated the changes of wax composition and structure, the
      related genes and WRI1 expression on Malus asiatica Nakai and sieversii fruits
      with the low temperature treatments, found that low temperature induced the up
      regulated expression of McWRI1, which promoted gene expression of McKCS, McLACs
      and McWAX in very-long-chain fatty acid biosynthesis pathway, resulting in the
      accumulation of alkanes component and alteration of wax structure on the fruit
      surface. Corresponding results were verified in McWRI1 silenced by VIGS, and WRI1
      silenced down-regulated the related genes on two kinds of fruits, it caused the
      diversity alteration in content of some alkanes, fatty acid and ester component
      in two kinds of fruits. We further conducted Y1H assay to find that McWRI1
      transcription factor activated the promoter of McKCS, McLAC and McWAX to regulate
      their expression. These results demonstrated that McWRI1 is involved in
      regulating the genes related synthesis of very long chain fatty acid on surface
      of apple fruits in storage process, providing a highlight for improvement of the
      modified atmosphere storage of apple fruits.

PMID- 29073206
TI  - Modeling the adenosine system as a modulator of cognitive performance and sleep
      patterns during sleep restriction and recovery.
AB  - Sleep loss causes profound cognitive impairments and increases the concentrations
      of adenosine and adenosine A1 receptors in specific regions of the brain. Time
      courses for performance impairment and recovery differ between acute and chronic
      sleep loss, but the physiological basis for these time courses is unknown.
      Adenosine has been implicated in pathways that generate sleepiness and cognitive
      impairments, but existing mathematical models of sleep and cognitive performance
      do not explicitly include adenosine. Here, we developed a novel receptor-ligand
      model of the adenosine system to test the hypothesis that changes in both
      adenosine and A1 receptor concentrations can capture changes in cognitive
      performance during acute sleep deprivation (one prolonged wake episode), chronic
      sleep restriction (multiple nights with insufficient sleep), and subsequent
      recovery. Parameter values were estimated using biochemical data and reaction
      time performance on the psychomotor vigilance test (PVT). The model closely fit
      group-average PVT data during acute sleep deprivation, chronic sleep restriction,
      and recovery. We tested the model's ability to reproduce timing and duration of
      sleep in a separate experiment where individuals were permitted to sleep for up
      to 14 hours per day for 28 days. The model accurately reproduced these data, and
      also correctly predicted the possible emergence of a split sleep pattern (two
      distinct sleep episodes) under these experimental conditions. Our findings
      provide a physiologically plausible explanation for observed changes in cognitive
      performance and sleep during sleep loss and recovery, as well as a new approach
      for predicting sleep and cognitive performance under planned schedules.

PMID- 29073209
TI  - Influence of main forcing affecting the Tagus turbid plume under high river
      discharges using MODIS imagery.
AB  - The role of river discharge, wind and tide on the extension and variability of
      the Tagus River plume was analyzed from 2003 to 2015. This study was performed
      combining daily images obtained from the Moderate Resolution Imaging
      Spectroradiometer (MODIS) sensor located onboard the Aqua and Terra satellites.
      Composites were generated by averaging pixels with the same forcing conditions.
      River discharge shows a strong relation with the extension of the Tagus plume.
      The plume grows with the increasing river discharge and express a two day lag
      caused by the long residence time of water within the estuary. The Tagus turbid
      plume was found to be smaller under northerly and easterly winds, than under
      southerly and westerly winds. It is suggested that upwelling favoring winds
      provoke the offshore movement of the plume material with a rapidly decrease in
      turbidity values whereas downwelling favoring winds retain plume material in the
      north coast close to the Tagus mouth. Eastern cross-shore (oceanward) winds
      spread the plume seaward and to the north following the coast geometry, whereas
      western cross-shore (landward) winds keep the plume material in both alongshore
      directions occupying a large part of the area enclosed by the bay. Low tides
      produce larger and more turbid plumes than high tides. In terms of fortnightly
      periodicity, the maximum plume extension corresponding to the highest turbidity
      is observed during and after spring tides. Minimum plume extension associated
      with the lowest turbidity occurs during and after neap tides.

PMID- 29073208
TI  - Pendular energy transduction within the step during human walking on slopes at
      different speeds.
AB  - When ascending (descending) a slope, positive (negative) work must be performed
      to overcome changes in gravitational potential energy at the center of body mass
      (COM). This modifies the pendulum-like behavior of walking. The aim of this study
      is to analyze how energy exchange and mechanical work done vary within a step
      across slopes and speeds. Ten subjects walked on an instrumented treadmill at
      different slopes (from -9 degrees  to 9 degrees ), and speeds (between 0.56 and
      2.22 m s-1). From the ground reaction forces, we evaluated energy of the COM,
      recovery (i.e. the potential-kinetic energy transduction) and pendular energy
      savings (i.e. the theoretical reduction in work due to this recovered energy)
      throughout the step. When walking uphill as compared to level, pendular energy
      savings increase during the first part of stance (when the COM is lifted) and
      decreases during the second part. Conversely in downhill walking, pendular energy
      savings decrease during the first part of stance and increase during the second
      part (when the COM is lowered). In uphill and downhill walking, the main phase of
      external work occurs around double support. Uphill, the positive work phase is
      extended during the beginning of single support to raise the body. Downhill, the
      negative work phase starts before double support, slowing the downward velocity
      of the body. Changes of the pendulum-like behavior as a function of slope can be
      illustrated by tilting the 'classical compass model' backwards (uphill) or
      forwards (downhill).

PMID- 29073207
TI  - Parallel mapping with site-directed hydroxyl radicals and micrococcal nuclease
      reveals structural features of positioned nucleosomes in vivo.
AB  - Micrococcal nuclease (MNase) has been widely used for analyses of nucleosome
      locations in many organisms. However, due to its sequence preference, the
      interpretations of the positions and occupancies of nucleosomes using MNase have
      remained controversial. Next-generation sequencing (NGS) has also been utilized
      for analyses of MNase-digests, but some technical biases are commonly present in
      the NGS experiments. Here, we established a gel-based method to map nucleosome
      positions in Saccharomyces cerevisiae, using isolated nuclei as the substrate for
      the histone H4 S47C-site-directed chemical cleavage in parallel with MNase
      digestion. The parallel mapping allowed us to compare the chemically and
      enzymatically cleaved sites by indirect end-labeling and primer extension
      mapping, and thus we could determine the nucleosome positions and the sizes of
      the nucleosome-free regions (or nucleosome-depleted regions) more accurately, as
      compared to nucleosome mapping by MNase alone. The analysis also revealed that
      the structural features of the nucleosomes flanked by the nucleosome-free region
      were different from those within regularly arrayed nucleosomes, showing that the
      structures and dynamics of individual nucleosomes strongly depend on their
      locations. Moreover, we demonstrated that the parallel mapping results were
      generally consistent with the previous genome-wide chemical mapping and MNase-Seq
      results. Thus, the gel-based parallel mapping will be useful for the analysis of
      a specific locus under various conditions.

PMID- 29073210
TI  - Monthly variations in aneurysmal subarachnoid hemorrhage incidence and mortality:
      Correlation with weather and pollution.
AB  - BACKGROUND AND PURPOSE: Although the effect of weather and air pollution on the
      occurrence of subarachnoid hemorrhage (SAH) has been investigated, results have
      remained inconsistent. The present study aimed to determine the seasonality of
      aneurysmal subarachnoid hemorrhage occurrence and mortality. METHODS: We used the
      National Inpatient Sample database to evaluate the effect of meteorological
      factors and air pollutants on patients with subarachnoid hemorrhage in Korea
      between 2011 and 2014. Monthly variations in SAH occurrence and mortality were
      analyzed using locally weighted scatter plot smoothing curves. Multivariate
      Poisson generalized linear regression models were used to evaluate potential
      independent meteorological and pollutant variables associated with SAH occurrence
      and mortality. RESULTS: In total, 21,407 patients who underwent clip or coil
      treatment owing to aneurysmal SAH in Korea from January 1, 2011, to December 31,
      2014, were included. The crude incidence rate of SAH in Korea was 10.5 per
      100,000 people per year. An approximately 0.5% lower risk of SAH was observed per
      1 degrees C increase in mean monthly temperature (relative risk, 0.995; 95%
      confidence interval [CI], 0.992-0.997; p < 0.001), while an approximately 2.3%
      higher risk of SAH was observed per 1 degrees C increase in mean monthly diurnal
      temperature. CONCLUSIONS: We showed distinct patterns of seasonal and monthly
      variation in the occurrence and mortality of SAH. Our findings suggest that
      meteorological factors may play an important role in monthly variations in the
      occurrence of aneurysmal SAH.

PMID- 29073211
TI  - High temperature enhances the ability of Trichoderma asperellum to infect
      Pleurotus ostreatus mycelia.
AB  - Trichoderma asperellum is one of the species which can be isolated from
      contaminated Pleurotus ostreatus cultivation substrate with green mold disease.
      This study focused on the relationship between high temperature and infectivity
      of T. asperellum to P. ostreatus. Antagonism experiments between T. asperellum
      and P. ostreatus mycelia revealed that high temperature-treated P. ostreatus
      mycelia were more easily infected by T. asperellum and covered by conidia.
      Microscopic observation also showed that P. ostreatus mycelia treated with high
      temperature could adsorb more T. asperellum conidia. Furthermore, conidia
      obtained from T. asperellum mycelia grown at 36 degrees C featured higher
      germination rate compared with that incubated at 28 degrees C. High temperature
      treated T. asperellum mycelia can produce conidia in shorter periods, and T.
      asperellum mycelia were less sensitive to high temperature than P. ostreatus.
      Deactivated P. ostreatus mycelia can induce T. asperellum cell wall-degrading
      enzymes (CWDEs) and P. ostreatus mycelia subjected to high temperature showed
      induced CWDEs more effective than those incubated at 28 degrees C. Moreover, T.
      asperellum showed higher CWDEs activity at high temperature. In dual cultures,
      hydrogen peroxide (H2O2) increased after 36 degrees C, and high concentration of
      H2O2 could significantly inhibit the growth of P. ostreatus mycelia. In summary,
      our findings indicated for the first time that high temperature can induce a
      series of mechanisms to enhance infection abilities of T. asperellum to P.
      ostreatus mycelia and to cause Pleurotus green mold disease.

PMID- 29073213
TI  - Cytokine-induced killer cells: A novel treatment for allergic airway
      inflammation.
AB  - The effectiveness of cytokine-induced killer (CIK) cells for treatment of cancers
      has long been appreciated. Here, we report for the first time that CIK cells can
      be applied to treat allergic airway inflammation. Adopting from an established
      protocol with some modifications, we generated CIK cells ex vivo from mouse T
      cells, and examined their effectiveness in treatment of allergic airway
      inflammation using the ovalbumin-induced model of allergic airway inflammation.
      Based upon evaluation of bronchoalveolar lavage cellularity, T helper type2
      cytokine levels and lung histology, all of which are important parameters for
      determining the severity of allergic airway inflammation, diseased mice treated
      with CIK cells showed significant reductions in all the parameters without any
      obvious adverse effects. Interestingly, the observed effects were comparable to
      those treated with dexamethasone. Thus, our study provides a novel application of
      CIK cells in treatment of allergic airway inflammation.

PMID- 29073212
TI  - Statins and new-onset atrial fibrillation in a cohort of patients with
      hypertension. Analysis of electronic health records, 2006-2015.
AB  - Hypertension is the most prevalent risk factor for new-onset atrial fibrillation
      (AF). But few studies have addressed the effect of statins on the incidence of
      this arrhythmia in patients with hypertension. This study aimed to evaluate the
      effect of statins on new-onset of this arrhythmia in a hypertensive population,
      accounting for AF risk. Data from the Information System for the Development of
      Research in Primary Care was used to recruit a retrospective cohort of >=55-year
      old hypertensive individuals with no ischemic vascular disease, in 2006-2007,
      followed up through 2015. The effect of initiating statin treatment on new-onset
      atrial fibrillation was assessed with Cox proportional hazards models adjusted by
      the propensity score of receiving statin treatment, in the overall study
      population and stratified by AF risk. Of 100 276 included participants, 9814
      initiated statin treatment. The AF incidence per 1000 person-years (95%
      confidence interval) was 12.5 (12.3-12.8). Statin use associated with a
      significant (9%) reduction in AF incidence. Differences in absolute AF incidence
      were higher in the highest AF risk subgroup, and the estimated number needed to
      treat to avoid one case was 720. The relative effect was poor, similar across
      groups, and non-significant, as was the association of statins with adverse
      effects. We found a limited protective effect of statins over new-onset AF in
      this hypertensive population with no ischemic vascular disease. If there is no
      further indication, hypertensive patients would not benefit from statin use
      solely for AF primary prevention.

PMID- 29073214
TI  - Robust gdf9 and bmp15 expression in the oocytes of ovotestes through the Figla
      independent pathway in the hermaphroditic black porgy, Acanthopagrus schlegelii.
AB  - More than 1,500 fish species are hermaphroditic, but no hermaphroditic lineage
      appears to be evolutionarily ancient in fishes. Thus, whether more than one sex
      at a time was present during the evolutionary shift from gonochorism to
      hermaphroditism in fishes is an intriguing question. Ectopic oocytes were created
      in the ovotestes of protandrous black porgy via the withdrawal of estradiol (E2)
      administration. These ectopic oocytes reprogrammed the surrounding cells, which
      changed from Sertoli cells to follicle-like cells. We observed that gdf9 and
      bmp15 expression was localized in the primary oocytes and gradually decreased
      after oocytes entered a secondary oocyte stage. Robust expression of gdf9 and
      bmp15 in ectopic oocytes was associated with the surrounding Sertoli cells.
      However, blocking Cyp19a1a activity and increasing androgen levels did not
      stimulate the expression of gdf9 and bmp15. Thus, the robust gdf9 and bmp15
      expression was not related to the inappropriate male microenvironment.
      Furthermore, in vitro data demonstrated that gdf9 and bmp15 were not downstream
      genes of Figla signaling. Therefore, our results suggest that there are two
      independent mechanisms, a Figla-dependent pathway and a Figla-independent
      pathway, by which oocyte-surrounding cells are altered from a male somatic fate
      to a female somatic fate. This functional switch might clarify how oocytes
      created an appropriate microenvironment during the transition from the ancient
      gonochorism to the present hermaphroditism.

PMID- 29073215
TI  - Toxoplasma gondii serine-protease inhibitor-1: A new adjuvant candidate for
      asthma therapy.
AB  - Serine-proteases are important players in the pathogenesis of asthma, promoting
      inflammation and tissue remodeling. It's also known that many serine protease
      inhibitors display immunomodulatory properties. TgPI-1 is a Toxoplasma gondii
      protein that exhibits broad spectrum inhibitory activity against serine
      proteases. In view of the increased prevalence of atopic disorders and the need
      to develop new treatment strategies we sought to investigate the potential of
      TgPI-1 for treating respiratory allergies. For this purpose, we developed a
      therapeutic experimental model. BALB/c mice were rendered allergic by
      intraperitoneal ovalbumin-alum sensitization and airway-challenged. Once the
      asthmatic phenotype was achieved, mice were intranasally treated with rTgPI-1
      alone or with a mixture of rTgPI-1 and ovalbumin (OVA). A week later mice were
      given a secondary aerosol challenge. Treatment with rTgPI-1 alone or co
      administered with OVA diminished bronchoalveolar eosinophilia, mucus production
      and peribronchial lung infiltration. This effect was accompanied by a lung
      resistance reduction of 26.3% and 50.3% respectively. Both treatments resulted in
      the production of lower levels of IL-4, IL-5, IFN-gamma and regulatory IL-10 by
      thoracic lymph node cells stimulated with OVA. Interestingly, significant
      decreases in OVA specific IgE and T cell proliferation, and increases in FoxP3+ T
      cells at local and systemic levels were only detected when the inhibitor was
      administered along with OVA. These results show that both rTgPI-1 treatments
      reduced asthma hallmarks. However, co-administration of the inhibitor with the
      allergen was more effective. Hence, rTgPI-1 emerges as a novel adjuvant candidate
      for asthma treatment.

PMID- 29073217
TI  - Design and synthesis of a fluorescent probe based on naphthalene anhydride and
      its detection of copper ions.
AB  - Copper, as the third most abundant transition metal ions of human, plays an
      essential role in the redox reaction, signal transduction, hematopoiesis, and
      other physiological processes. Abnormal content of copper ions in the body will
      cause some diseases such as anemia, coronary heart disease, Menkes' syndrome. In
      this article, a new fluorescence probe L for Cu2+ was designed and synthetized by
      using 4-bromo-1,8 naphthalene anhydride and 2-thiophene formaldehyde as raw
      materials. Fluorescent probe L itself exhibited strong fluorescence, upon the
      addition of Cu2+ ions, the fluorescence was quenched. The fluorescent detection
      limit for Cu2+ ions was determined to be 1.8 MUM based on a 3delta/S method. UV
      vis absorption and fluorescence spectra indicated that probe L showed good
      selectivity and sensitivity for Cu2+, and this selectivity was not interfered by
      other metal ions and anions. Further cell fluorescence imaging experiments
      indicated that the probe L had potential to be used to examine copper ions in
      vivo.

PMID- 29073216
TI  - Prolonged immune alteration following resolution of acute inflammation in humans.
AB  - Acute inflammation is an immediate response to infection and injury characterised
      by the influx of granulocytes followed by phagocytosing mononuclear phagocytes.
      Provided the antigen is cleared and the immune system of the host is fully
      functional, the acute inflammatory response will resolve. Until now it is
      considered that resolution then leads back to homeostasis, the physiological
      state tissues experienced before inflammation occurred. Using a human model of
      acute inflammation driven by intradermal UV killed Escherichia coli, we found
      that bacteria and granulocyte clearance as well as pro-inflammatory cytokine
      catabolism occurred by 72h. However, following a lag phase of about 4 days there
      was an increase in numbers of memory T cells and CD163+ macrophage at the post
      resolution site up to day 17 as well as increased biosynthesis of cyclooxygenase
      derived prostanoids and DHA-derived D series resolvins. Inhibiting post
      resolution prostanoids using naproxen showed that numbers of tissue memory CD4
      cells were under the endogenous control of PGE2, which exerts its suppressive
      effects on T cell proliferation via the EP4 receptor. In addition, we re
      challenged the post-resolution site with a second injection of E. coli, which
      when compared to saline controls resulted in primarily a macrophage-driven
      response with comparatively fewer PMNs; the macrophage-dominated response was
      reversed by cyclooxygenase inhibition. Re-challenge experiments were also carried
      out in mice where we obtained similar results as in humans. Therefore, we report
      that acute inflammatory responses in both humans and rodents do not revert back
      to homeostasis, but trigger a hitherto unappreciated sequence of immunological
      events that dictate subsequent immune response to infection.

PMID- 29073218
TI  - Secondary analysis of hospital patient experience scores across England's
      National Health Service - How much has improved since 2005?
AB  - OBJECTIVE: To examine trends in patient experience and consistency between
      hospital trusts and settings. METHODS: Observational study of publicly available
      patient experience surveys of three hospital settings (inpatients (IP), accident
      and emergency (A&E) and outpatients (OP)) of 130 acute NHS hospital trusts in
      England between 2004/05 and 2014/15. RESULTS: Overall patient experience has been
      good, showing modest improvements over time across the three hospital settings.
      Individual questions with the biggest improvement across all three settings are
      cleanliness (IP: +7.1, A&E: +6.5, OP: +4.7) and information about danger signals
      (IP: +3.8, A&E: +3.9, OP: +4.0). Trust performance has been consistent over time:
      71.5% of trusts ranked in the same cluster for more than five years. There is
      some consistency across settings, especially between outpatients and inpatients.
      The lowest-scoring questions, regarding information at discharge, are the same in
      all years and all settings. CONCLUSIONS: The greatest improvement across all
      three settings has been for cleanliness, which has seen national policies and
      targets. Information about danger signals and medication side-effects showed
      least consistency across settings and scores have remained low over time, despite
      information about danger signals showing a big increase in score. Patient
      experience of aspects of access and waiting have declined, as has experience of
      discharge delay, likely reflecting known increases in pressure on England's NHS.

PMID- 29073219
TI  - Environmental enrichment accelerates ocular dominance plasticity in mouse visual
      cortex whereas transfer to standard cages resulted in a rapid loss of increased
      plasticity.
AB  - In standard cage (SC) raised mice, experience-dependent ocular dominance (OD)
      plasticity in the primary visual cortex (V1) rapidly declines with age: in
      postnatal day 25-35 (critical period) mice, 4 days of monocular deprivation (MD)
      are sufficient to induce OD-shifts towards the open eye; thereafter, 7 days of MD
      are needed. Beyond postnatal day 110, even 14 days of MD failed to induce OD
      plasticity in mouse V1. In contrast, mice raised in a so-called "enriched
      environment" (EE), exhibit lifelong OD-plasticity. EE-mice have more voluntary
      physical exercise (running wheels), and experience more social interactions
      (bigger housing groups) and more cognitive stimulation (regularly changed
      labyrinths or toys). Whether experience-dependent shifts of V1-activation happen
      faster in EE-mice and how long the plasticity promoting effect would persist
      after transferring EE-mice back to SCs has not yet been investigated. To this
      end, we used intrinsic signal optical imaging to visualize V1-activation i)
      before and after MD in EE-mice of different age groups (from 1-9 months), and ii)
      after transferring mice back to SCs after postnatal day 130. Already after 2 days
      of MD, and thus much faster than in SC-mice, EE-mice of all tested age groups
      displayed a significant OD-shift towards the open eye. Transfer of EE-mice to SCs
      immediately abolished OD-plasticity: already after 1 week of SC-housing and MD,
      OD-shifts could no longer be visualized. In an attempt to rescue abolished OD
      plasticity of these mice, we either administered the anti-depressant fluoxetine
      (in drinking water) or supplied a running wheel in the SCs. OD-plasticity was
      only rescued for the running wheel- mice. Altogether our results show that
      raising mice in less deprived environments like large EE-cages strongly
      accelerates experience-dependent changes in V1-activation compared to the
      impoverished SC-raising. Furthermore, preventing voluntary physical exercise of
      EE-mice in adulthood immediately precludes OD-shifts in V1.

PMID- 29073220
TI  - Life's Simple 7 and ischemic heart disease in the general Australian population.
AB  - BACKGROUND: The American Heart Association released 7 modifiable factors, Life's
      Simple 7, that are expected to improve cardiovascular health (CVH), but their
      contributions to ischemic heart disease (IHD) in the general Australians are not
      well clarified. METHODS: We performed a cross-sectional study based on 7499
      adults (>=18 years) who have tested for total cholesterol and fasting plasma
      glucose as part of 2011-12 Australian Health Survey. Poisson regression analyses
      were used to estimate the incidence rate ratios and population attributable
      fractions of those factors to IHD prevalence. Participants were classified into
      three CVH groups based on the number of ideal metrics: inadequate (0-2), average
      (3-4), and optimal (5-7). Logistic regression analyses were performed to
      elucidate the relationship between overall CVH and IHD prevalence. RESULTS: 357
      participants were self-reported having IHD condition, with a weighted prevalence
      of 3.3%. Physical inactivity, elevated body mass index (BMI) and total
      cholesterol (TC) were independently associated with IHD. Compared to the
      inadequate category, participants in the optimal and average categories have a
      78% [adjusted odds ratio (OR), 0.22; 95% confidence interval (CI), 0.03-1.96] and
      a 45% (adjusted OR, 0.55; 95% CI, 0.39-0.77) lower IHD risk. One more optimal
      metric was associated with an 18% lower IHD risk (adjusted OR, 0.82; 95% CI, 0.71
      0.93). CONCLUSIONS: Our findings indicate that physical inactivity, raised BMI
      and elevated TC were independent modifiable risk factors of IHD in the general
      Australian population. The improvement of overall CVH may also reduce IHD risk
      among the general Australian adults.

PMID- 29073221
TI  - Distinct retrosplenial cortex cell populations and their spike dynamics during
      ketamine-induced unconscious state.
AB  - Ketamine is known to induce psychotic-like symptoms, including delirium and
      visual hallucinations. It also causes neuronal damage and cell death in the
      retrosplenial cortex (RSC), an area that is thought to be a part of high visual
      cortical pathways and at least partially responsible for ketamine's
      psychotomimetic activities. However, the basic physiological properties of RSC
      cells as well as their response to ketamine in vivo remained largely unexplored.
      Here, we combine a computational method, the Inter-Spike Interval Classification
      Analysis (ISICA), and in vivo recordings to uncover and profile excitatory cell
      subtypes within layers 2&3 and 5&6 of the RSC in mice within both conscious,
      sleep, and ketamine-induced unconscious states. We demonstrate two distinct
      excitatory principal cell sub-populations, namely, high-bursting excitatory
      principal cells and low-bursting excitatory principal cells, within layers 2&3,
      and show that this classification is robust over the conscious states, namely
      quiet awake, and natural unconscious sleep periods. Similarly, we provide
      evidence of high-bursting and low-bursting excitatory principal cell sub
      populations within layers 5&6 that remained distinct during quiet awake and sleep
      states. We further examined how these subtypes are dynamically altered by
      ketamine. During ketamine-induced unconscious state, these distinct excitatory
      principal cell subtypes in both layer 2&3 and layer 5&6 exhibited distinct
      dynamics. We also uncovered different dynamics of local field potential under
      various brain states in layer 2&3 and layer 5&6. Interestingly, ketamine
      administration induced high gamma oscillations in layer 2&3 of the RSC, but not
      layer 5&6. Our results show that excitatory principal cells within RSC layers 2&3
      and 5&6 contain multiple physiologically distinct sub-populations, and they are
      differentially affected by ketamine.

PMID- 29073223
TI  - Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid
      concentrations and lower risk of urine stone formation in cats.
AB  - The lifespan of cats with non-obstructive kidney stones is shortened compared
      with healthy cats indicating a need to reduce stone formation and minimize
      chronic kidney disease. The purpose of this study was to investigate the effects
      of increasing dietary polyunsaturated fatty acids (PUFA) on urine
      characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years) were
      randomized into two groups and fed one of two dry-cat foods in a cross-over study
      design. For one week before study initiation, all cats consumed control food that
      contained 0.07% arachidonic acid (AA), but no eicosapentaenoic acid (EPA) or
      docosahexaenoic acid (DHA). Group 1 continued eating control food for 56 days.
      Group 2 was fed test food for 56 days, which was control food plus fish oil and
      high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56
      days, cats were fed the opposite food for another 56 days. At baseline and after
      each feeding period, serum was analyzed for fatty acid concentrations, and urine
      for specific gravity, calcium concentration, relative-super-saturation for
      struvite crystals, and a calcium-oxalate-titrimetric test was performed. After
      consuming test food, cats had increased (all P<0.001) serum concentrations of EPA
      (173%), DHA (61%), and AA (35%); decreased urine specific gravity (P = 0.02);
      decreased urine calcium concentration (P = 0.06); decreased relative-super
      saturation for struvite crystals (P = 0.03); and increased resistance to oxalate
      crystal formation (P = 0.06) compared with cats consuming control food. Oxalate
      crystal formation was correlated with serum calcium concentration (r = 0.41;
      P<0.01). These data show benefits for reducing urine stone formation in cats by
      increasing dietary PUFA.

PMID- 29073222
TI  - Maternal experience of intimate partner violence and low birth weight of
      children: A hospital-based study in Bangladesh.
AB  - OBJECTIVE: Intimate partner violence (IPV) is the most prevalent form of gender
      based violence worldwide. IPV either before or during pregnancy has been
      documented as a risk factor for the health of the mother and her unborn child.
      The aim of this study was to examine the relationship between maternal experience
      of IPV and low birth weight (LBW). STUDY DESIGN: A hospital-based survey was
      conducted among women in the postnatal wards of a large public hospital at
      Rajshahi, Bangladesh. Data on socio-economic characteristics, reproductive health
      characteristics, intimate partner violence, and antenatal, delivery and newborn
      care were collected from 400 women between July 2015 and April 2016. RESULTS:
      Results of this study indicated that 43% of women reported experiencing any
      physical IPV in their lifetime, 35.5% of them experienced sexual IPV, and 32.5%
      experienced both physical and sexual IPV. Approximately one in every three
      (29.2%) infants was born with LBW. Physical IPV was associated with an increased
      risk of having a child with low birth weight (adjusted odds ratio [AOR]: 3.01,
      95% CI: 2.35-5.81). The risk of infants born with LBW increased with women's
      lifetime experience of sexual IPV (AOR: 1.98; 95% CI: 1.23-4.15) and both
      physical and sexual IPV (AOR: 4.05; 95% CI: 2.79-7.33). CONCLUSION: Maternal
      lifetime experience of IPV is positively associated with LBW children. Preventing
      women from the experience of IPV may help improve neonatal and child mortality in
      Bangladesh.

PMID- 29073224
TI  - Diversification dynamics, species sorting, and changes in the functional
      diversity of marine benthic gastropods during the Pliocene-Quaternary at
      temperate western South America.
AB  - Functional diversity based on species traits is a powerful tool to investigate
      how changes in species richness and composition affect ecosystem functioning.
      However, studies aimed at understanding changes in functional diversity over
      large temporal and spatial scales are still scant. Here we evaluate the combined
      effect of diversification and species sorting on functional diversity of fossil
      marine gastropods during the Pliocene-Quaternary transition in the Pacific coast
      of South America. We analyzed a total of 172 species in 29 Pliocene and 97
      Quaternary sites. Each species was characterized according to six functional
      traits: body size, feeding type, mobility, attachment, life-habit, and larval
      mode. Functional diversity was estimated according to four indexes (functional
      richness, evenness, divergence and dispersion) based on functional traits
      measured. Extrapolated species richness showed a slight yet not significant
      decrease from the Pliocene to the Quaternary despite the fact that a large faunal
      turnover took place; furthermore, a large extinction of Pliocene species (61-76%)
      was followed by a high pulse of appearances (49-56%) during the Quaternary. Three
      out of four indices of functional diversity (evenness, divergence and dispersion)
      increased significantly towards the Quaternary which is more than expected under
      a random turnover of species. The increase in functional diversity is associated
      with a loss of large-sized carnivore forms, which tended to be replaced by small
      sized grazers. Hence, this trait-selective species turnover, even in the absence
      of significant changes in species richness, likely had a large effect and has
      shaped the functional diversity of present-day assemblages.

PMID- 29073225
TI  - Correction: Author contributions to ecological publications: What does it mean to
      be an author in modern ecological research?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179956.].

PMID- 29073226
TI  - Behavioral correlates of cheating: Environmental specificity and reward
      expectation.
AB  - Academic dishonesty has been and continues to be a major problem in America's
      schools and universities. Such dishonesty is especially important in high
      schools, where grades earned directly impact the academic careers of students for
      many years to come. The rising pressure to get the best grades in school, get
      into the best college, and land the best paying job is a cycle that has made
      academic dishonesty increase exponentially. Thus, finding the widespread roots of
      cheating is more important now than ever. In this study, we focus on how societal
      norms and interactions with peers influence lying about scores in order to obtain
      a benefit in a high school population. We show that (1) the societal norms that
      go hand in hand with test-taking in school, as administered by a teacher,
      significantly dampen small-scale dishonesty, perhaps suggesting that context
      dependent rewards offset cheating; (2) providing reminders of societal norms via
      pre-reported average scores leads to more truthful self-reporting of honesty; (3)
      the matrix search task was shown to not depend on class difficulty, confirming
      its effectiveness as an appropriate method for this study; (4) males seem to
      cheat more than females; and (5) teenagers are more dishonest earlier in the day.
      We suggest that students understand that cheating is wrong, an idea backed up by
      the literature, and that an environment which clearly does not condone dishonesty
      helps dampen widespread cheating in certain instances. This dampening effect
      seems to be dependent on the reward that students thought they would get for
      exaggerating their performance.

PMID- 29073227
TI  - The methylenetetrahydrofolate reductase c.c.677 C>T and c.c.1298 A>C
      polymorphisms in reproductive failures: Experience from an RSA and RIF study on a
      Polish population.
AB  - Almost 1600 individuals from the Polish population were recruited to this study.
      Among them 319 were fertile couples, 289 were recurrent spontaneous abortion
      (RSA) couples, and 131 were in the group of recurrent implantation failure (RIF)
      following in vitro fertilization. The aim of this study was to evaluate the MTHFR
      c.c.677 C>T and c.c.1298 A>C polymorphisms' association with RSA and RIF. We used
      PCR-RFLP with HinfI (677 C>T) and MboII (1298 A>C) digestion. We observed a
      protective effect of the female AC genotype (OR = 0.64, p = 0.01) and the C
      allele (AC+CC genotypes; OR = 0.65, p = 0.009) against RSA. Moreover, 1298 AA/677
      CT women were more frequent in RSA (31.14%) and RIF (25.20%) groups in comparison
      to fertile women (22.88%), although this difference was significant only in the
      case of RSA (p = 0.022, OR = 1.52). Male combined genotype analysis revealed no
      association with reproductive failure of their partners. Nevertheless, the
      female/male combination AA/AC of the 1298 polymorphism was more frequent in RSA
      couples (p = 0.049, OR = 1.49). However, the significant results became
      insignificant after Bonferroni correction. In addition, analysis of haplotypes
      showed significantly higher frequency of the C/C haplotype (1298 C/677 C) in the
      female control group than in the female RSA group (p = 0.03, OR = 0.77).
      Moreover, the association between elevated homocysteine (Hcy) level in plasma of
      RSA and RIF women and MTHFR polymorphisms was investigated but did not reveal
      significant differences. In conclusion, for clinical practice, it is better to
      check the homocysteine level in plasma and, if the Hcy level is increased, to
      recommend patients to take folic acid supplements rather than undergo screening
      of MTHFR for 1298 A>C and 677 C>T polymorphisms.

PMID- 29073228
TI  - Using a whole-body 31P birdcage transmit coil and 16-element receive array for
      human cardiac metabolic imaging at 7T.
AB  - PURPOSE: Cardiac phosphorus magnetic resonance spectroscopy (31P-MRS) provides
      unique insight into the mechanisms of heart failure. Yet, clinical applications
      have been hindered by the restricted sensitivity of the surface radiofrequency
      coils normally used. These permit the analysis of spectra only from the
      interventricular septum, or large volumes of myocardium, which may not be
      meaningful in focal disease. Loring et al. recently presented a prototype whole
      body (52 cm diameter) transmit/receive birdcage coil for 31P at 7T. We now
      present a new, easily-removable, whole-body 31P transmit radiofrequency-coil
      built into a patient-bed extension combined with a 16-element receive array for
      cardiac 31P-MRS. MATERIALS AND METHODS: A fully-removable (55 cm diameter)
      birdcage transmit coil was combined with a 16-element receive array on a Magnetom
      7T scanner (Siemens, Germany). Electro-magnetic field simulations and phantom
      tests of the setup were performed. In vivo maps of B1+, metabolite signals, and
      saturation-band efficiency were acquired across the torsos of eight volunteers.
      RESULTS: The combined (volume-transmit, local receive array) setup increased
      signal-to-noise ratio 2.6-fold 10 cm below the array (depth of the
      interventricular septum) compared to using the birdcage coil in transceiver mode.
      The simulated coefficient of variation for B1+ of the whole-body coil across the
      heart was 46.7% (surface coil 129.0%); and the in vivo measured value was 38.4%.
      Metabolite images of 2,3-diphosphoglycerate clearly resolved the ventricular
      blood pools, and muscle tissue was visible in phosphocreatine (PCr) maps.
      Amplitude-modulated saturation bands achieved 71+/-4% suppression of
      phosphocreatine PCr in chest-wall muscles. Subjects reported they were
      comfortable. CONCLUSION: This easy-to-assemble, volume-transmit, local receive
      array coil combination significantly improves the homogeneity and field-of-view
      for metabolic imaging of the human heart at 7T.

PMID- 29073229
TI  - Effect of a package of integrated demand- and supply-side interventions on
      facility delivery rates in rural Bangladesh: Implications for large-scale
      programs.
AB  - BACKGROUND: According to the Bangladesh Demographic and Health Survey 2014, only
      approximately 37 percent of women deliver in a health facility. Among the eight
      administrative divisions of Bangladesh, the facility delivery rate is lowest in
      the Sylhet division (22.6 percent) where we assessed the effect of integrated
      supply- and demand-side interventions on the facility-based delivery rate.
      METHODS: Population-based cohort data of pregnant women from an ongoing maternal
      and newborn health improvement study being conducted in a population of ~120,000
      in Sylhet district were used. The study required collection and processing of
      biological samples immediately after delivery. Therefore, the project assembled
      various strategies to increase institutional delivery rates. The supply-side
      intervention included capacity expansion of the health facilities through service
      provider refresher training, 24/7 service coverage, additions of drugs and
      supplies, and incentives to the providers. The demand-side component involved
      financial incentives to cover expenses, a provision of emergency transport, and
      referral support to a tertiary-level hospital. We conducted a before-and-after
      observational study to assess the impact of the intervention in a total of 1,861
      deliveries between December 2014 and November 2016. RESULTS: Overall,
      implementation of the intervention package was associated with 52.6 percentage
      point increase in the proportions of facility-based deliveries from a baseline
      rate of 25.0 percent to 77.6 percent in 24 months. We observed lower rates of
      institutional deliveries when only supply-side interventions were implemented.
      The proportion rose to 47.1 percent and continued increasing when the project
      emphasized addressing the financial barriers to accessing obstetric care in a
      health facility. CONCLUSIONS: An integrated supply- and demand-side intervention
      was associated with a substantial increase in institutional delivery. The package
      can be tailored to identify which combination of interventions may produce the
      optimum result and be scaled. Rigorous implementation research studies are needed
      to draw confident conclusions and to provide information about the costs,
      feasibility for scale-up and sustainability.

PMID- 29073230
TI  - Spatial and temporal trends in fin whale vocalizations recorded in the NE Pacific
      Ocean between 2003-2013.
AB  - In order to study the long-term stability of fin whale (Balaenoptera physalus)
      singing behavior, the frequency and inter-pulse interval of fin whale 20 Hz
      vocalizations were observed over 10 years from 2003-2013 from bottom mounted
      hydrophones and seismometers in the northeast Pacific Ocean. The instrument
      locations extended from 40 degrees N to 48 degrees N and 130 degrees W to 125
      degrees W with water depths ranging from 1500-4000 m. The inter-pulse interval
      (IPI) of fin whale song sequences was observed to increase at a rate of 0.54
      seconds/year over the decade of observation. During the same time period, peak
      frequency decreased at a rate of 0.17 Hz/year. Two primary call patterns were
      observed. During the earlier years, the more commonly observed pattern had a
      single frequency and single IPI. In later years, a doublet pattern emerged, with
      two dominant frequencies and IPIs. Many call sequences in the intervening years
      appeared to represent a transitional state between the two patterns. The overall
      trend was consistent across the entire geographical span, although some regional
      differences exist. Understanding changes in acoustic behavior over long time
      periods is needed to help establish whether acoustic characteristics can be used
      to help determine population identity in a widely distributed, difficult to study
      species such as the fin whale.

PMID- 29073231
TI  - Poly(ADP-ribose)polymerases inhibitors prevent early mitochondrial fragmentation
      and hepatocyte cell death induced by H2O2.
AB  - Poly(ADP-ribose)polymerases (PARPs) are a family of NAD+ consuming enzymes that
      play a crucial role in many cellular processes, most clearly in maintaining
      genome integrity. Here, we present an extensive analysis of the alteration of
      mitochondrial morphology and the relationship to PARPs activity after oxidative
      stress using an in vitro model of human hepatic cells. The following outcomes
      were observed: reactive oxygen species (ROS) induced by oxidative treatment
      quickly stimulated PARPs activation, promoted changes in mitochondrial morphology
      associated with early mitochondrial fragmentation and energy dysfunction and
      finally triggered apoptotic cell death. Pharmacological treatment with specific
      PARP-1 (the major NAD+ consuming poly(ADP-ribose)polymerases) and PARP-1/PARP-2
      inhibitors after the oxidant insult recovered normal mitochondrial morphology
      and, hence, increased the viability of human hepatic cells. As the PARP-1 and
      PARP-1/PARP-2 inhibitors achieved similar outcomes, we conclude that most of the
      PARPs effects were due to PARP-1 activation. NAD+ supplementation had similar
      effects to those of the PARPs inhibitors. Therefore, PARPs activation and the
      subsequent NAD+ depletion are crucial events in decreased cell survival (and
      increased apoptosis) in hepatic cells subjected to oxidative stress. These
      results suggest that the alterations in mitochondrial morphology and function
      seem to be related to NAD+ depletion, and show for the first time that PARPs
      inhibition abrogates mitochondrial fragmentation. In conclusion, the inhibition
      of PARPs may be a valuable therapeutic approach for treating liver diseases, by
      reducing the cell death associated with oxidative stress.

PMID- 29073232
TI  - Artificial induction of third-stage dispersal juveniles of Bursaphelenchus
      xylophilus using newly established inbred lines.
AB  - The pine wood nematode, Bursaphelenchus xylophilus, is the causal agent of pine
      wilt disease. This nematode has two developmental forms in its life cycle; i.e.,
      the propagative and dispersal forms. The former is the form that builds up its
      population inside the host pine. The latter is specialized for transport by the
      vector. This form is separated into two dispersal stages (third and fourth); the
      third-stage dispersal juvenile (JIII) is specialized for survival under
      unfavorable conditions, whereas the fourth-stage juvenile (JIV), which is induced
      by a chemical signal from the carrier Monochamus beetle, is transported to new
      host pines and invades them. Because of its importance in the disease cycle,
      molecular and chemical aspects of the JIV have been investigated, while the
      mechanism of JIII induction has not been sufficiently investigated. In an effort
      to clarify the JIII induction process, we established inbred lines of B.
      xylophilus and compared their biological features. We found that the total number
      of nematodes (propagation proportion) was negatively correlated with the JIII
      emergence proportion, likely because nematode development was arrested at JIII;
      i.e., they could not develop to adults via the reproductive stage. In addition,
      JIII induction seemed to be regulated by a small number of genes because the JIII
      induction proportion varied among inbred lines despite the high homozygosity of
      the parental line. We also demonstrated that JIII can be artificially induced by
      the nematode's secreted substances. This is the first report of artificial
      induction of JIII in B. xylophilus. The dauer (dispersal) juvenile of the model
      organism Caenorhabditis elegans corresponds functionally to JIII of B.
      xylophilus, and this stage is known to be induced by a chemical signal referred
      to as daumone, derived from the nematodes' secretion. The artificial induction of
      JIII suggests the presence of daumone-like material in B. xylophilus.

PMID- 29073234
TI  - The effects of patient cost sharing on inpatient utilization, cost, and outcome.
AB  - BACKGROUND: Health insurance and provider payment reforms all over the world beg
      a key empirical question: what are the potential impacts of patient cost-sharing
      on health care utilization, cost and outcomes? The unique health insurance system
      and rich electronic medical record (EMR) data in China provides us a unique
      opportunity to study this topic. METHODS: Four years (2010 to 2014) of EMR data
      from one medical center in China were utilized, including 10,858 adult patients
      with liver diseases. We measured patient cost-sharing using actual reimbursement
      ratio (RR) which is allowed us to better capture financial incentive than using
      type of health insurance. A rigorous risk adjustment method was employed with
      both comorbidities and disease severity measures acting as risk adjustors.
      Associations between RR and health use, costs and outcome were analyzed by
      multivariate analyses. RESULTS: After risk adjustment, patients with more
      generous health insurance coverage (higher RR) were found to have longer hospital
      stay, higher total cost, higher medication cost, and higher ratio of medication
      to total cost, as well as higher number and likelihood that specific procedures
      were performed. CONCLUSION: Our study implied that patient cost-sharing affects
      health care services use and cost. This reflects how patients and physicians
      respond to financial incentives in the current healthcare system in China, and
      the responses could be a joint effect of both demand and supply side moral
      hazard. In order to contain cost and improve efficiency in the system, reforming
      provide payment and insurance scheme is urgently needed.

PMID- 29073233
TI  - Transcriptional and post-translational changes in the brain of mice deficient in
      cholesterol removal mediated by cytochrome P450 46A1 (CYP46A1).
AB  - Cytochrome P450 46A1 (CYP46A1) converts cholesterol to 24-hydroxycholesterol and
      thereby controls the major pathways of cholesterol removal from the brain.
      Cyp46a1-/- mice have a reduction in the rate of cholesterol biosynthesis in the
      brain and significant impairments to memory and learning. To gain insights into
      the mechanisms underlying Cyp46a1-/- phenotype, we used Cyp46a1-/- mice and
      quantified their brain sterol levels and the expression of the genes pertinent to
      cholesterol homeostasis. We also compared the Cyp46a1-/- and wild type brains for
      protein phosphorylation and ubiquitination. The data obtained enable the
      following inferences. First, there seems to be a compensatory upregulation in the
      Cyp46a1-/- brain of the pathways of cholesterol storage and CYP46A1-independent
      removal. Second, transcriptional regulation of the brain cholesterol biosynthesis
      via sterol regulatory element binding transcription factors is not significantly
      activated in the Cyp46a1-/- brain to explain a compensatory decrease in
      cholesterol biosynthesis. Third, some of the liver X receptor target genes
      (Abca1) are paradoxically upregulated in the Cyp46a1-/- brain, possibly due to a
      reduced activation of the small GTPases RAB8, CDC42, and RAC as a result of a
      reduced phosphorylation of RAB3IP and PAK1. Fourth, the phosphorylation of many
      other proteins (a total of 146) is altered in the Cyp46a1-/- brain, including
      microtubule associated and neurofilament proteins (the MAP and NEF families)
      along with proteins related to synaptic vesicles and synaptic neurotransmission
      (e.g., SLCs, SHANKs, and BSN). Fifth, the extent of protein ubiquitination is
      increased in the Cyp46a1-/- brain, and the affected proteins pertain to
      ubiquitination (UBE2N), cognition (STX1B and ATP1A2), cytoskeleton function
      (TUBA1A and YWHAZ), and energy production (ATP1A2 and ALDOA). The present study
      demonstrates the diverse potential effects of CYP46A1 deficiency on brain
      functions and identifies important proteins that could be affected by this
      deficiency.

PMID- 29073235
TI  - Src-family kinases negatively regulate NFAT signaling in resting human T cells.
AB  - T cell signaling is required for activation of both natural and therapeutic T
      cells including chimeric antigen receptor (CAR) T cells. Identification of novel
      factors and pathways regulating T cell signaling may aid in development of
      effective T cell therapies. In resting human T cells, the majority of Src-family
      of tyrosine kinases (SFKs) are inactive due to phosphorylation of a conserved
      carboxy-terminal tyrosine residue. Recently, a pool of enzymatically active SFKs
      has been identified in resting T cells; however, the significance of these is
      incompletely understood. Here, we characterized the role of active SFKs in
      resting human T cells. Pharmacologic inhibition of active SFKs enhanced distal
      TCR signaling as measured by IL-2 release and CD25 surface expression following
      TCR-independent activation. Mechanistically, inhibition of the active pool of
      SFKs induced nuclear translocation of NFAT1, and enhanced NFAT1-dependent
      signaling in resting T cells. The negative regulation of NFAT1 signaling was in
      part mediated by the Src-kinase Lck as human T cells lacking Lck had increased
      levels of nuclear NFAT1 and demonstrated enhanced NFAT1-dependent gene
      expression. Inhibition of active SFKs in resting primary human T cells also
      increased nuclear NFAT1 and enhanced NFAT1-dependent signaling. Finally, the
      calcineurin inhibitor FK506 and Cyclosporin A reversed the effect of SFKs
      inhibition on NFAT1. Together, these data identified a novel role of SFKs in
      preventing aberrant NFAT1 activation in resting T cells, and suggest that
      maintaining this pool of active SFKs in therapeutic T cells may increase the
      efficacy of T cell therapies.

PMID- 29073236
TI  - Prevalence of peripheral artery disease (PAD) and factors associated: An
      epidemiological analysis from the population-based Screening PRE-diabetes and
      type 2 DIAbetes (SPREDIA-2) study.
AB  - AIM: To describe the prevalence of Peripheral Artery Disease (PAD) in a random
      population sample and to evaluate its relationship with Mediterranean diet and
      with other potential cardiovascular risk factors such as serum uric acid and
      pulse pressure in individuals ranged 45 to 74 years. METHODS: Cross-sectional
      analysis of 1568 subjects (mean age 6.5 years, 43% males), randomly selected from
      the population. A fasting blood sample was obtained to determine glucose, lipids,
      and HbA1C levels. An oral glucose tolerance test was performed in non-diabetic
      subjects. PAD was evaluated by ankle-brachial index and/or having a prior
      diagnosis. RESULTS: PAD prevalence was 3.81% (95% CI, 2.97-4.87) for all
      participants. In men, PAD prevalence was significantly higher than in women
      [5.17% (95% CI, 3.74-7.11) vs. 2.78% (95% CI, 1.89-4.07); p = 0.014]. Serum uric
      acid in the upper quartile was associated with the highest odds ratio (OR) of PAD
      (for uric acid > 6.1 mg/dl, OR = 4.31; 95% CI, 1.49-12.44). The remaining
      variables more strongly associated with PAD were: Heart rate >90 bpm (OR = 4.16;
      95%CI, 1.62-10.65), pulse pressure in the upper quartile (>= 54 mmHg) (OR = 3.82;
      95%CI, 1.50-9.71), adherence to Mediterranean diet (OR = 2.73; 95% CI, 1.48
      5.04), and former smoker status (OR = 2.04; 95%CI, 1.00-4.16). CONCLUSIONS: Our
      results show the existence of a low prevalence of peripheral artery disease in a
      population aged 45-74 years. Serum uric acid, pulse pressure and heart rate >90
      bpm were strongly associated with peripheral artery disease. The direct
      association between Mediterranean diet and peripheral artery disease that we have
      found should be evaluated through a follow-up study under clinical practice
      conditions.

PMID- 29073237
TI  - Physical activity and cohabitation status moderate the link between diabetes
      mellitus and cognitive performance in a community-dwelling elderly population in
      Germany.
AB  - AIMS/HYPOTHESIS: The increasing number of people with dementia and cognitive
      impairments makes it essential to detect and prevent modifiable risk factors of
      dementia. This study focuses on type 2 diabetes mellitus, especially on
      undiagnosed cases and their increased risk of cognitive impairment. Furthermore,
      the potential of physical activity and social integration to moderate the
      relation between diabetes and cognitive impairment is assessed. METHODS: We used
      cross-sectional data from 1299 participants of the Berlin Aging Study II (BASE
      II) aged between 60 to 84 years and performed logistic regression models to
      analyze the association of diabetes status, physical activity, and cohabitation
      status with poor cognitive performance. Cognitive performance was measured with
      the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Plus test
      battery. RESULTS: Undiagnosed diabetes (odds ratio (OR) = 2.12, p = 0.031),
      physical inactivity (OR = 1.43, p = 0.008) and non-cohabiting (OR = 1.58, p =
      0.002) were associated with an increased likelihood of poor cognitive
      performance. The highest odds were observed in participants who suffered from
      undiagnosed or insulin-dependent diabetes and, in addition, were inactive
      (undiagnosed diabetes: OR = 3.44, p = 0.003; insulin-dependent diabetes: OR =
      6.19, p = 0.019) or lived alone (undiagnosed diabetes: OR = 4.46, p = 0.006;
      insulin-dependent diabetes: OR = 6.46 p = 0.052). Physical activity and
      cohabiting appeared to be beneficial. CONCLUSIONS/INTERPRETATION: Physical
      activity and cohabitation status moderate the link between diabetes mellitus and
      cognitive performance. Special attention should be paid to undiagnosed and
      insulin-dependent diabetes cases, which have a particularly high risk of poor
      cognitive performance.

PMID- 29073238
TI  - Genetic variations, reproductive aging, and breast cancer risk in African
      American and European American women: The Women's Circle of Health Study.
AB  - Reproductive aging phenotypes, including age at menarche (AM) and age at natural
      menopause (ANM), are well-established risk factors for breast cancer. In recent
      years, many genetic variants have been identified in association with AM and ANM
      in genome-wide association studies among European populations. Using data from
      the Women's Circle of Health Study (WCHS) of 1,307 European-American (EA) and
      1,365 African-American (AA) breast cancer cases and controls, we aimed to
      replicate 53 earlier GWAS variants for AM and ANM in AA and EA groups and to
      perform analyses on total and net reproductive lifespan (TRLS; NRLS). Breast
      cancer risk was also examined in relation to a polygenic risk score (PRS) for
      each of the reproductive aging phenotypes. We replicated a number of variants in
      EA women, including rs7759938 in LIN28B for AM and rs16991615 in MCM8 for ANM;
      whereas in the AA group, only one SNP (rs2947411 in TMEM18) for AM was
      directionally consistent and nominally significant. In analysis of TRLS and NRLS,
      several SNPs were significant, including rs466639 in RXRG that was associated
      with both phenotypes in both AA and EA groups. None of the PRS was associated
      with breast cancer risk. Given the paucity of data available among AA
      populations, our study contributes to the literature of genetics of reproductive
      aging in AA women and highlights the importance of cross population replication
      of GWAS variants.

PMID- 29073239
TI  - Seasonal variation in non-structural carbohydrates, sucrolytic activity and
      secondary metabolites in deciduous and perennial Diospyros species sampled in
      Western Mexico.
AB  - This study was performed to test the working hypothesis that the primary
      determinants influencing seasonal driven modifications in carbon mobilization and
      other key biochemical parameters in leaves of poorly known Diospyros digyna (Ddg;
      semi-domesticated; perennial) and D. rekoi (Dre; undomesticated; deciduous) trees
      are determined by environmental growing conditions, agronomic management and
      physiological plasticity. Thus, biochemical changes in leaves of both trees were
      recorded seasonally during two successive fruiting years. Trees were randomly
      sampled in Western Mexico habitats with differing soil quality, climatic
      conditions, luminosity, and cultivation practices. Leaves of Ddg had consistently
      higher total chlorophyll contents (CT) that, unexpectedly, peaked in the winter
      of 2015. In Dre, the highest leaf CT values recorded in the summer of 2015
      inversely correlated with low average luminosity and high Chl a/ Chlb ratios. The
      seasonal CT variations in Dre were congruent with varying luminosity, whereas
      those in Ddg were probably affected by other factors, such as fluctuating leaf
      protein contents and the funneling of light energy to foliar non-structural
      carbohydrates (NSCs) accumulation, which were consistently higher than those
      detected in Dre leaves. Seasonal foliar NSC fluctuations in both species were in
      agreement with the carbon (C) demands of flowering, fruiting and/ or leaf
      regrowth. Seasonal changes in foliar hexose to sucrose (Hex/ Suc) ratios
      coincided with cell wall invertase activity in both species. In Dre, high Hex/
      Suc ratios in spring leaves possibly allowed an accumulation of phenolic acids,
      not observed in Ddg. The above results supported the hypothesis proposed by
      showing that leaf responses to changing environmental conditions differ in
      perennial and deciduous Diospyros trees, including a dynamic adjustment of NSCs
      to supply the C demands imposed by reproduction, leaf regrowth and, possibly,
      stress.

PMID- 29073240
TI  - The course of the radial nerve in the distal humerus: A novel, anatomy based,
      radiographic assessment.
AB  - METHODS AND FINDINGS: Measurements were done on both arms of ten specially
      embalmed specimens. Arms were dissected and radiopaque wires attached to the
      radial nerve in the distal part of the upper arm. Digital radiographs were
      obtained to determine the course of the radial nerve in the distal 20 cm of the
      humerus in relation to bony landmarks; medial epicondyle and capitellum-trochlea
      projection (CCT). Analysis was done with ImageJ and Microsoft Excel software. We
      also compared humeral nail specifications from different companies with the
      course of the radial nerve to predict possible radial nerve damage. RESULTS: The
      distance from the medial epicondyle to point where the radial nerve bends from
      posterior to lateral was 142 mm on AP radiographs and 152 mm measured on the
      lateral radiographs. The average distance from the medial epicondyle to point
      where the radial nerve bends from lateral to anterior on AP radiographs was 66
      mm. On the lateral radiographs where the nerve moves away from the anterior
      cortex 83 mm to the center of capitellum and trochlea (CCT). The distance from
      the bifurcation of the radial nerve into the posterior interosseous nerve (PIN)
      and superficial radial nerve was 21 mm on AP radiographs and 42 mm on the lateral
      radiographs (CCT). CONCLUSIONS: The course of the radial nerve in the distal part
      of the upper arm has great variety. Lateral fixation is relatively safe in a zone
      between the center of capitellum-trochlea and 48 mm proximal to this point. The
      danger zone in lateral fixation is in-between 48-122 mm proximal from CCT. In
      anteroposterior direction; distal fixation is dangerous between 21-101 mm
      measured from the medial epicondyle. The more distal, the more medial the nerve
      courses making it more valuable to iatrogenic damage. The IMN we compared with
      our data all show potential risk in case of (blind) distal locking, especially
      from lateral to medial direction.

PMID- 29073241
TI  - Detection of trace concentrations of S-nitrosothiols by means of a capacitive
      sensor.
AB  - Small molecule S-nitrosothiols are a class of endogenous chemicals in the body,
      which have been implicated in a variety of biological functions. However, the
      labile nature of NO and the limits of current detection assays have made studying
      these molecules difficult. Here we present a method for detecting trace
      concentrations of S-nitrosothiols in biological fluids. Capacitive sensors when
      coupled to a semiconducting material represent a method for detecting trace
      quantities of a chemical in complex solutions. We have taken advantage of the
      semiconducting and chemical properties of polydopamine to construct a capacitive
      sensor and associated method of use, which specifically senses S-nitrosothiols in
      complex biological solutions.

PMID- 29073242
TI  - Clinical features of superficial and deep peripapillary microvascular density in
      healthy myopic eyes.
AB  - PURPOSE: To evaluate the clinical features of peripapillary microvasculature in
      myopic eyes and investigate the association between the superficial and deep
      peripapillary microvascular density and the myopic optic disc characteristics.
      MATERIALS AND METHODS: This cross-sectional study included one hundred and fifty
      healthy myopic eyes with beta-peripapillary atrophy (beta-PPA). Ovality index,
      degree of optic disc rotation, and the area of beta-PPA were measured.
      Superficial and deep peripapillary microvascular density was measured using
      optical coherence tomography angiography. Logistic regression analysis was
      performed to look for the factors associated with peripapillary microvascular
      reduction. RESULTS: The mean superficial peripapillary microvascular density was
      62.14 +/- 5.47%; 33 (22.0%) participants were found to have decreased
      microvascular density. Increased axial length (p < 0.001) and decreased average
      peripapillary retinal nerve fiber layer thickness (p = 0.027) were associated
      with the superficial peripapillary microvascular reduction. The mean deep
      peripapillary microvascular density was 73.76 +/- 4.02%; 26 (17.33%) participants
      were found to have decreased microvascular density. Larger ovality index (p =
      0.028) and more inferiorly rotated optic disc (p = 0.021) were associated with
      the deep peripapillary microvascular reduction. CONCLUSIONS: Axial elongation was
      significantly associated with microvascular reduction in the superficial
      peripapillary retina, whereas it was not associated with deep peripapillary
      microvascular reduction. The deep peripapillary microvascular density was
      independently associated with myopic optic disc characteristics such as ovality
      index and optic disc rotation.

PMID- 29073243
TI  - RNA-seq transcriptome analysis of formalin fixed, paraffin-embedded canine
      meningioma.
AB  - Meningiomas are the most commonly reported primary intracranial tumor in dogs and
      humans and between the two species there are similarities in histology and
      biologic behavior. Due to these similarities, dogs have been proposed as models
      for meningioma pathobiology. However, little is known about specific pathways and
      individual genes that are involved in the development and progression of canine
      meningioma. In addition, studies are lacking that utilize RNAseq to characterize
      gene expression in clinical cases of canine meningioma. The primary objective of
      this study was to develop a technique for which high quality RNA can be extracted
      from formalin-fixed, paraffin embedded tissue and then used for transcriptome
      analysis to determine patterns of gene expression. RNA was extracted from
      thirteen canine meningiomas-eleven from formalin fixed and two flash-frozen.
      These represented six grade I and seven grade II meningiomas based on the World
      Health Organization classification system for human meningioma. RNA was also
      extracted from fresh frozen leptomeninges from three control dogs for comparison.
      RNAseq libraries made from formalin fixed tissue were of sufficient quality to
      successfully identify 125 significantly differentially expressed genes, the
      majority of which were related to oncogenic processes. Twelve genes (AQP1, BMPER,
      FBLN2, FRZB, MEDAG, MYC, PAMR1, PDGFRL, PDPN, PECAM1, PERP, ZC2HC1C) were
      validated using qPCR. Among the differentially expressed genes were oncogenes,
      tumor suppressors, transcription factors, VEGF-related genes, and members of the
      WNT pathway. Our work demonstrates that RNA of sufficient quality can be
      extracted from FFPE canine meningioma samples to provide biologically relevant
      transcriptome analyses using a next-generation sequencing technique, such as RNA
      seq.

PMID- 29073244
TI  - Resveratrol controlled the fate of porcine pancreatic stem cells through the
      Wnt/beta-catenin signaling pathway mediated by Sirt1.
AB  - Porcine pancreatic stem cells (PSCs) are considered promising transplant
      materials that may be used to treat diabetes, but some problems, such as
      insufficient cell number and low differentiation efficiency, should be solved
      before its clinical application. Resveratrol is a natural polyphenolic compound
      that can alleviate the complications of diabetes. In this study, we aimed to
      explore the specific effect of resveratrol on porcine PSCs. We treated porcine
      PSCs with 10 MUM, 25 MUM resveratrol to explore the effect of resveratrol on
      porcine PSCs. We found that 10 MUM resveratrol improved the proliferation of
      porcine PSCs, increased the expression of A-beta-catenin (active beta-catenin),
      Pcna, C-Myc, Bcl-2 and sirtuin-1 (Sirt1), and decreased the expression of P53,
      Caspase3. While 25 MUM resveratrol had almost opposite effect compared with 10
      MUM resveratrol group. The utilization of Dickkopf-related protein 1 (DKK1, Wnt
      signaling pathway inhibitor) and nicotinamide (Sirt1 inhibitor) suggested that
      resveratrol regulated cell proliferation by controlling Wnt signaling pathway and
      this effect was mediated by Sirt1. Our results further revealed that 10 MUM
      resveratrol promoted the formation of beta-like cells regulated by Wnt/beta
      catenin signal pathway. Relatively low-dose resveratrol could improve porcine
      PSCs fate. It lays theoretical foundation for diabetes treatment with cell
      transplantation in future.

PMID- 29073247
TI  - Evaluation of the nitrogen content during the new-shoot-growing stage in apple
      leaves using two-dimensional correlation spectroscopy.
AB  - The new-shoot-growing stage is an important period of apple tree nutrition
      distribution. The objective of this study is to provide technical support for
      apple tree nutrition diagnosis by constructing quantitative evaluation models
      between the apple leaf nitrogen content during the new-shoot-growing stage and
      characteristic spectral parameters. The correlation coefficients between the
      original spectral data and the nitrogen content were calculated. Then, the
      sensitive bands of the nitrogen content were selected using the theory of two
      dimensional (2D) correlation spectroscopy. Finally, partial least squares
      regression (PLSR) and support vector machine (SVM) evaluation models were
      established using 2 parameters: Rx (maximum spectral reflectivity in the
      waveband) and Sx (total spectral reflectivity in the waveband). The results
      showed that the sensitive bands in the 2D correlation synchronous and
      asynchronous spectrograms were 537-560 nm and 708-719 nm. The PLSR model can be
      used to estimate the nitrogen content. Compared with PLSR, SVM provided better
      modeling and testing results, with a larger coefficient of determination (R2) and
      a smaller root-mean-square error (RMSE). The SVM model based on Sx was a good
      backup method. The calibration R2 of the model was 0.821, its RMSE was 0.710 g.kg
      1, the validation R2 was 0.768, and its RMSE was 1.019 g.kg-1. The SVM model
      based on 2D correlation spectroscopy can be used to quantitatively estimate the
      nitrogen content in apple leaves.

PMID- 29073246
TI  - Increased serum anti-N-methyl-D-aspartate receptor antibody immunofluorescence in
      psychiatric patients with past catatonia.
AB  - OBJECTIVE: Anti-N-methyl-D-aspartate receptor (NMDAR) antibody was thought to be
      the cause of anti-NMDAR encephalitis, with manifestations similar to catatonia
      and schizophrenia. Anti-NMDAR antibody in neuropsychiatric patients who had
      catatonia before were investigated in a follow-up evaluation. The intensity of
      antibody immunofluorescence was quantified and compared with healthy controls.
      METHOD: Nineteen patients (eight males and eleven females) agreed to be followed
      up. Thirteen had the diagnosis of schizophrenia, two had the diagnosis of major
      depressive disorder, two had bipolar disorder, one had postpartum depression, and
      one had herpes simplex encephalitis. No patient had catatonia during the follow
      up. Nineteen sex-matched healthy controls were recruited. RESULTS: Using Mann
      Whitney U test, patients had greater intensity of anti-NMDAR antibody
      immunofluorescence than the healthy controls (121,979 +/- 86,526 vs. 47,692 +/-
      26,102, p = 0.003). No correlation was found between immunofluorescence intensity
      and catatonia scales or symptom severity scores. Neuropsychiatric patients with
      past catatonia showed greater anti-NMDAR antibody response than the healthy
      controls. CONCLUSION: NMDAR dysfunction might play a role in the mechanism
      underlying catatonia. Further studies are needed to confirm this finding.

PMID- 29073248
TI  - Yersinia pestis strains of ancient phylogenetic branch 0.ANT are widely spread in
      the high-mountain plague foci of Kyrgyzstan.
AB  - Fifty six Yersinia pestis strains, isolated over the period of more than 50 years
      in three high-mountain foci of Kyrgyzstan (Tien Shan, Alai, and Talas), have been
      characterized by means of PCR and single nucleotide polymorphism (SNP) typing
      methods. Seven of these strains were also characterized by means of whole genome
      sequencing and genome-wide SNP phylogenetic analysis. It was found that forty two
      strains belong to 0.ANT2, 0.ANT3 and 0.ANT5 phylogenetic branches. From these,
      strains of 0.ANT2 and 0.ANT3 branches were earlier detected in China only,
      whereas 0.ANT5 phylogenetic branch was identified for Y. pestis phylogeny for the
      first time. According to the results of genome-wide SNP analysis, 0.ANT5 strains
      are ones of the most closely related to Y. pestis strain responsible for the
      Justinianic Plague. We have also found out that four of the studied strains
      belong to the phylogenetic branch 2.MED1, and ten strains from Talas high
      mountain focus belong to the phylogenetic branch 0.PE4 (sub-branch 0.PE4t).
      Established diversity of Y. pestis strains and extensive dissemination of the
      strains pertaining to the 0.ANT branch confirm the antiquity of the mentioned
      above plague foci and suggest that strains of the 0.ANT branch, which serve as
      precursors for all highly virulent Y. pestis strains, had their origin in the
      Tien Shan mountains.

PMID- 29073245
TI  - Abomasal dysfunction and cellular and mucin changes during infection of sheep
      with larval or adult Teladorsagia circumcincta.
AB  - This is the first integrated study of the effects on gastric secretion,
      inflammation and fundic mucins after infection with L3 T. circumcincta and in the
      very early period following transplantation of adult worms. At 3 months-of-age,
      20 Coopworth lambs were infected intraruminally with 35,000 L3; infected animals
      were killed on Days 5, 10, 15, 20 and 30 post-infection and 6 controls on either
      Day 0 or 30 post-infection. Another 15 Romney cross lambs received 10,000 adult
      worms at 4-5 months-of-age though surgically-implanted abomasal cannulae and were
      killed after 6, 12, 24 and 72 hours; uninfected controls were also killed at 72
      hours. Blood was collected at regular intervals from all animals for measurement
      of serum gastrin and pepsinogen and abomasal fluid for pH measurement from
      cannulated sheep. Tissues collected at necropsy were fixed in Bouin's fluid for
      light microscopy, immunocytochemistry and mucin staining and in Karnovsky's fluid
      for electron microscopy. Nodules around glands containing developing larvae were
      seen on Day 5 p.i., but generalised effects on secretion occurred only after
      parasite emergence and within hours after transplantation of adult worms. After
      L3 infection, there were maximum worm burdens on Days 10-15 post-infection,
      together with peak tissue eosinophilia, inhibition of gastric acid secretion,
      hypergastrinaemia, hyperpepsinogenaemia, loss of parietal cells, enlarged gastric
      pits containing less mucin and increased numbers of mucous neck cells. After
      adult transplantation, serum pepsinogen was significantly increased after 9 hours
      and serum gastrin after 18 hours. Parallel changes in host tissues and the
      numbers of parasites in the abomasal lumen suggest that luminal parasites, but
      not those in the tissues, are key drivers of the pathophysiology and inflammatory
      response in animals exposed to parasites for the first time. These results are
      consistent with initiation of the host response by parasite chemicals diffusing
      across the surface epithelium, possibly aided by components of ES products which
      increased permeability. Parietal cells appear to be a key target, resulting in
      secondary increases in serum gastrin, pit elongation, loss of surface mucins and
      inhibition of chief cell maturation. Inflammation occurs in parallel, and could
      either cause the pathology or exacerbate the direct effects of ES products.

PMID- 29073249
TI  - Association of birth weight with corneal power in early adolescence: Results from
      the National Health and Nutrition Examination Survey (NHANES) 1999-2008.
AB  - PURPOSE: To analyze the effect of birth weight on ocular morphology, refraction
      and visual function in early adolescents aged 12-15 years. MATERIAL AND METHODS:
      We conducted a secondary data analysis using the public use files from the
      National Health and Nutrition Examination Survey of the period from 1999 to 2008.
      Study participants aged 12 to 15 years were included with data on birth weight
      and ophthalmic parameters including presenting distance visual acuity, objective
      refraction and keratometry. Visual acuity, sphere, astigmatism in power vectors
      J0 and J45, corneal power and corneal astigmatism were evaluated for an
      association with birth weight. Linear and logistic regression with adjustment for
      age, sex, ethnicity, survey cycle and birth weight as independent variable were
      calculated. RESULTS: Linear regression analysis revealed an association between
      corneal power and birth weight (per 100g: beta = -0.04, p<0.001) in the
      univariate analysis, and in the model adjusted for age, sex, ethnicity and NHANES
      survey cycle (per 100g: beta = -0.04, p<0.001). A lower birth weight was
      associated with higher corneal power. We found no evidence for an association of
      visual acuity, sphere, spherical equivalent, J0-vector and J45-vector of
      astigmatism, corneal J0- or corneal J45-vector with birth weight. CONCLUSION: Our
      data demonstrate that low BW is linked to alterations in keratometric power even
      in early adolescents aged 12-15 years whereas visual acuity and refractive error
      showed no association.

PMID- 29073250
TI  - Effects of physiatrist and registered therapist operating acute rehabilitation
      (PROr) in patients with stroke.
AB  - OBJECTIVE: Clinical evidence suggests that early mobilization of patients with
      acute stroke improves activity of daily living (ADL). The purpose of this study
      was to compare the utility of the physiatrist and registered therapist operating
      acute rehabilitation (PROr) applied early or late after acute stroke. SUBJECTS
      AND METHODS: This study was prospective cohort study, assessment design. Patients
      with acute stroke (n = 227) admitted between June 2014 and April 2015 were
      divided into three groups based on the time of start of PROr: within 24 hours
      (VEM, n = 47), 24-48 hours (EM, n = 77), and more than 48 hours (OM, n = 103)
      from stroke onset. All groups were assessed for the number of deaths during
      hospitalization, and changes in the Glasgow Coma Scale (GCS), National Institute
      of Health Stroke Scale (NIHSS), and Functional Independence Measure (FIM) at
      hospital discharge. INTERVENTIONS: All patients were assessed by physiatrists,
      who evaluated the specific needs for rehabilitation, and then referred them to
      registered physical therapists and occupational therapists to provide early
      mobilization (longer than one hour per day per patient). RESULTS: The number of
      deaths encountered during the PROr period was 13 (out of 227, 5.7%), including 2
      (4.3%) in the VEM group. GCS improved significantly during the hospital stay in
      all three groups, but the improvement on discharge was significantly better in
      the VEM group compared with the EM and OM groups. FIM improved significantly in
      the three groups, and the gains in total FIM and motor subscale were
      significantly greater in the VEM than the other groups. CONCLUSIONS: PROr seems
      safe and beneficial rehabilitation to improve ADL in patients with acute stroke.

PMID- 29073252
TI  - Severity of coronary artery disease is associated with non-alcoholic fatty liver
      dis-ease: A single-blinded prospective mono-center study.
AB  - BACKGROUND AND AIMS: Liver steatosis has shown to be associated with coronary
      artery disease (CAD). The aim of our study was to evaluate the association
      between the presence and severity of CAD and Non-alcoholic fatty liver disease
      (NAFLD) assessed by transient elastography (TE) and controlled attenuation
      parameter (CAP). METHODS: 576 Patients undergoing coronary angiography were
      enrolled in this prospective study, receiving at least 10 TE and CAP measurements
      using the FibroScan(r) M-probe. Clinically relevant CAD (CAD 3) was defined as
      stenosis with >=75% reduction of the luminal diameter. NAFLD was determined by
      CAP >=234 dB/m. NAFLD with advanced fibrosiswas determined by TE-values >=7.9kPa
      in the presence of NAFLD and absence of congestive or right-sided heart failure.
      Rates and 95% confidence intervals are shown. RESULTS: 505 patients were
      available for analysis of NAFLD. However, only 392 patients were available for
      analysis of NAFLD with advanced fibrosis, since 24 patients had to be excluded
      due to non valid TE-measurements and 89 patients due to congestive or right-sided
      heart failure or suspected concomitant liver disease, respectively. 70.5% (66.3%
      74.4%) of patients had CAD 3, 71.5% (67.3%-75.4%) were diagnosed with NAFLD, and
      11.2% (8.3%-14.8%) with NAFLD with advanced fibrosis. Patients with CAD 3 had
      higher median CAP-values (273+/-61 vs. 260+/-66 dB/m; p = 0.038) and higher
      degrees of steatosis as compared to patients without CAD 3. While NAFLD was
      significantly more often diagnosed in patients with CAD 3 (75.0% vs. 63.1%, p =
      0.0068), no significant difference was found for NAFLD with advanced fibrosis
      (10.7% vs. 12.5%, p = 0.60). CONCLUSIONS: Clinically relevant CAD is frequently
      associated with the presence of NAFLD, but not NAFLD with advanced fibrosis.

PMID- 29073251
TI  - Single-cell analysis identifies cellular markers of the HIV permissive cell.
AB  - Cellular permissiveness to HIV infection is highly heterogeneous across
      individuals. Heterogeneity is also found across CD4+ T cells from the same
      individual, where only a fraction of cells gets infected. To explore the basis of
      permissiveness, we performed single-cell RNA-seq analysis of non-infected CD4+ T
      cells from high and low permissive individuals. Transcriptional heterogeneity
      translated in a continuum of cell states, driven by T-cell receptor-mediated cell
      activation and was strongly linked to permissiveness. Proteins expressed at the
      cell surface and displaying the highest correlation with T cell activation were
      tested as biomarkers of cellular permissiveness to HIV. FACS sorting using
      antibodies against several biomarkers of permissiveness led to an increase of HIV
      cellular infection rates. Top candidate biomarkers included CD25, a canonical
      activation marker. The combination of CD25 high expression with other candidate
      biomarkers led to the identification of CD298, CD63 and CD317 as the best
      biomarkers for permissiveness. CD25highCD298highCD63highCD317high cell population
      showed an enrichment of HIV-infection of up to 28 fold as compared to the
      unsorted cell population. The purified hyper-permissive cell subpopulation was
      characterized by a downregulation of interferon-induced genes and several known
      restriction factors. Single-cell RNA-seq analysis coupled with functional
      characterization of cell biomarkers provides signatures of the "HIV-permissive
      cell".

PMID- 29073253
TI  - Nrf2 is highly expressed in neutrophils, but myeloid cell-derived Nrf2 is
      dispensable for wound healing in mice.
AB  - Immune cells of the myeloid lineage are key players in skin wound healing, since
      they secrete various cytokines and growth factors that orchestrate the repair
      process. In addition, they are crucial for the defense against invading pathogens
      through their capacity to produce high levels of reactive oxygen species (ROS).
      To limit the toxicity of ROS, cells have developed antioxidant defense
      strategies, including expression of the cytoprotective NRF2 transcription factor.
      Here we show that murine neutrophils and to a lesser extent macrophages strongly
      express Nrf2 already when present in the circulation and in particular at the
      wound site. To determine the role of Nrf2 in neutrophils and macrophages for
      wound repair, we generated mice with a gain- or loss-of-function of this
      transcription factor in the myeloid cell lineage. Expression of a constitutively
      active Nrf2 mutant in myeloid cells did not further enhance the overall Nrf2
      activity in these cells due to the already high steady-state activity of
      endogenous Nrf2. Surprisingly, deletion of Nrf2 in myeloid cells only mildly
      affected the levels of ROS and the expression of pro-inflammatory cytokines by
      these cells. In particular, various parameters of wound healing, including wound
      closure, reepithelialization, wound contraction and the presence of myeloid cells
      at the wound site were not affected. These results reveal that Nrf2 in myeloid
      cells is dispensable for wound healing and suggest the presence of additional
      antioxidant defense strategies of these cells that compensate for the loss of
      Nrf2, even in the harsh environment of skin wounds.

PMID- 29073254
TI  - Combining MAD and CPAP as an effective strategy for treating patients with severe
      sleep apnea intolerant to high-pressure PAP and unresponsive to MAD.
AB  - INTRODUCTION: This study aimed to determine the effect of combining positive
      airway pressure (PAP) therapy and mandibular advancement device (MAD) in patients
      with severe obstructive sleep apnea (OSA) who were pressure intolerant for PAP
      and were unresponsive to MAD. METHODS: This retrospective study reviewed the
      medical records of severe OSA patients with apnea-hypopnea index (AHI) >= 30/hr
      who were diagnosed between October 1, 2008 and June 30, 2014. Patients were
      initially treated with 2 weeks of PAP, and those who were intolerant to high
      pressure PAP (>=15 cm H2O) were switched to 12 weeks of MAD, which is a monobloc
      designed at 75% of maximum protrusion. Patients who had high residual AHI
      (>=15/hr) on MAD underwent 12 weeks of combination therapy (CT) with MAD and CPAP
      and were enrolled in the present study. Enrolled subjects who completed the 12
      week CT were followed-up until June 30, 2016. RESULTS: A total of 14 male
      patients were included. All three treatments effectively reduced AHI, oxygen
      desaturation index (ODI), and total sleep time with SpO2 <90% (% TST-SpO2<90%)
      compared to pretreatment values. The residual AHI and ODI on CT was lower than
      that on MAD or PAP. The residual % TST-SpO2<90% was lower than that on MAD and
      similar to that on PAP. The therapeutic pressure on CT was on average 9.2 cm H2O
      lower than that on PAP. For the 11 patients who completed CT, only CT reduced ESS
      compared to pretreatment value. No treatment had significant impact on % slow
      wave sleep or overnight change of blood pressure. For patients who completed CT,
      the average usage was 5.9+/-1.7 hr/night at 12th week and 6.4+/-1.5 hr/night at a
      median follow-up of 36.5-months. CONCLUSIONS: Combining MAD and CPAP showed
      additive effects on reducing AHI and ODI, and lowered the therapeutic pressures.

PMID- 29073256
TI  - Cost effectiveness analysis comparing repetitive transcranial magnetic
      stimulation to antidepressant medications after a first treatment failure for
      major depressive disorder in newly diagnosed patients - A lifetime analysis.
AB  - OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) commonly is used
      for the treatment of Major Depressive Disorder (MDD) after patients have failed
      to benefit from trials of multiple antidepressant medications. No analysis to
      date has examined the cost-effectiveness of rTMS used earlier in the course of
      treatment and over a patients' lifetime. METHODS: We used lifetime Markov
      simulation modeling to compare the direct costs and quality adjusted life years
      (QALYs) of rTMS and medication therapy in patients with newly diagnosed MDD (ages
      20-59) who had failed to benefit from one pharmacotherapy trial. Patients' life
      expectancies, rates of response and remission, and quality of life outcomes were
      derived from the literature, and treatment costs were based upon published
      Medicare reimbursement data. Baseline costs, aggregate per year quality of life
      assessments (QALYs), Monte Carlo simulation, tornado analysis, assessment of
      dominance, and one way sensitivity analysis were also performed. The discount
      rate applied was 3%. RESULTS: Lifetime direct treatment costs, and QALYs
      identified rTMS as the dominant therapy compared to antidepressant medications
      (i.e., lower costs with better outcomes) in all age ranges, with costs/improved
      QALYs ranging from $2,952/0.32 (older patients) to $11,140/0.43 (younger
      patients). One-way sensitivity analysis demonstrated that the model was most
      sensitive to the input variables of cost per rTMS session, monthly prescription
      drug cost, and the number of rTMS sessions per year. CONCLUSION: rTMS was
      identified as the dominant therapy compared to antidepressant medication trials
      over the life of the patient across the lifespan of adults with MDD, given
      current costs of treatment. These models support the use of rTMS after a single
      failed antidepressant medication trial versus further attempts at medication
      treatment in adults with MDD.

PMID- 29073255
TI  - Serosurveillance for pandemic influenza A (H1N1) 2009 virus infection in domestic
      elephants, Thailand.
AB  - The present study conducted serosurveillance for the presence of antibody to
      pandemic influenza A (H1N1) 2009 virus (H1N1pdm virus) in archival serum samples
      collected between 2009 and 2013 from 317 domestic elephants living in 19
      provinces situated in various parts of Thailand. To obtain the most accurate
      data, hemagglutination-inhibition (HI) assay was employed as the screening test;
      and sera with HI antibody titers >=20 were further confirmed by other methods,
      including cytopathic effect/hemagglutination based-microneutralization (microNT)
      and Western blot (WB) assays using H1N1pdm matrix 1 (M1) or hemagglutinin (HA)
      recombinant protein as the test antigen. Conclusively, the appropriate assays
      using HI in conjunction with WB assays for HA antibody revealed an overall
      seropositive rate of 8.5% (27 of 317). The prevalence of antibody to H1N1pdm
      virus was 2% (4/172) in 2009, 32% (17/53) in 2010, 9% (2/22) in 2011, 12% (1/8)
      in 2012, and 5% (3/62) in 2013. Notably, these positive serum samples were
      collected from elephants living in 7 tourist provinces of Thailand. The highest
      seropositive rate was obtained from elephants in Phuket, a popular tourist beach
      city. Young elephants had higher seropositive rate than older elephants. The
      source of H1N1pdm viral infection in these elephants was not explored, but most
      likely came from close contact with the infected mahouts or from the infected
      tourists who engaged in activities such as elephant riding and feeding.
      Nevertheless, it could not be excluded that elephant-to-elephant transmission did
      occur.

PMID- 29073257
TI  - Efficacy and safety of anatomic resection versus nonanatomic resection in
      patients with hepatocellular carcinoma: A systemic review and meta-analysis.
AB  - BACKGROUND: The surgical decision of performing anatomic resection (AR) or
      nonanatomic resection (NAR) in patients with hepatocellular carcinoma remains
      controversial. The aim of the current study is to conduct a meta-analysis on
      published results to compare surgical outcomes after AR and NAR. METHODS: A
      comprehensive search of the Pubmed, Ovid-Medline, Embase, Cochrane library, and
      Science Citation indexes was performed. Overall and disease free survival (DFS),
      perioperative mortality and morbidity were the main outcomes. The meta-analysis
      was performed using Revman 5.3 statistical software, and the results are
      expressed as the relative risk (RR) or weighted mean differences with 95% of
      confidence intervals. RESULTS: After application of the exclusion and inclusion
      criteria, 25 studies published between 1996~2015 that compared outcomes after AR
      and NAR in patients with HCC were identified. A total of 10216 patients were
      included in the meta-analysis, 4576 in the AR group and 5640 in the NAR group.
      Liver cirrhosis was found in 54.8% (range from 18.8% to 100%) of patients in the
      AR group and 67.8% (range from 34.3% to 100%) of patients in the NAR group,
      resulting in a RR of 0.45 (I2 = 18%, fixed model, 95% CI 0.39-0.52; Z = 10.31; P
      = <0.00001). The meta-analysis revealed a statistically significant 5-year
      survival (RR of 1.10, 95% CI 1.03-1.17; Z = 2.92, P = 0.004) and DFS (RR: 1.33,
      95% CI 1.18-1.51; Z = 4.46, P <0.00001) advantage for patients undergoing AR
      resection compared to NAR. In regards to safety, no statistical significance was
      found in mortality and morbidity between the two groups. Eight studies including
      1812 patients with small (<5 cm) solitary HCC indicated a better 5-year DFS in
      the AR group (41.4%) than in the NAR group (28.6%), with a RR of 1.32 (I2 = 42,
      fixed model, 95%CI: 1.15-1.52, Z = 3.86, P = 0.0001). CONCLUSION: The current
      study demonstrates better surgical outcomes after AR than NAR in patients with
      HCC. Therefore, AR is recommended in resectable HCC, especially with small (<5
      cm) solitary tumours.

PMID- 29073259
TI  - Effect of climatic variability on childhood diarrhea and its high risk periods in
      northwestern parts of Ethiopia.
AB  - BACKGROUND: Increasing climate variability as a result of climate change will be
      one of the public health challenges to control infectious diseases in the future,
      particularly in sub-Saharan Africa including Ethiopia. OBJECTIVE: To investigate
      the effect of climate variability on childhood diarrhea (CDD) and identify high
      risk periods of diarrheal diseases. METHODS: The study was conducted in all
      districts located in three Zones (Awi, West and East Gojjam) of Amhara Region in
      northwestern parts of Ethiopia. Monthly CDD cases for 24 months (from July 2013
      to June 2015) reported to each district health office from the routine
      surveillance system were used for the study. Temperature, rainfall and humidity
      data for each district were extracted from satellite precipitation estimates and
      global atmospheric reanalysis. The space-time permutation scan statistic was used
      to identify high risk periods of CDD. A negative binomial regression was used to
      investigate the relationship between cases of CDD and climate variables.
      Statistical analyses were conducted using SaTScan program and StataSE v. 12.
      RESULTS: The monthly average incidence rate of CDD was 11.4 per 1000 (95%CI 10.8
      12.0) with significant variation between males [12.5 per 1000 (95%CI 11.9 to
      13.2)] and females [10.2 per 1000 (95%CI 9.6 to 10.8)]. The space-time
      permutation scan statistic identified the most likely high risk period of CDD
      between March and June 2014 located in Huletej Enese district of East Gojjam
      Zone. Monthly average temperature and monthly average rainfall were positively
      associated with the rate of CDD, whereas the relative humidity was negatively
      associated with the rate of CDD. CONCLUSIONS: This study found that the most
      likely high risk period is in the beginning of the dry season. Climatic factors
      have an association with the occurrence of CDD. Therefore, CDD prevention and
      control strategy should consider local weather variations to improve programs on
      CDD.

PMID- 29073258
TI  - Pegivirus avoids immune recognition but does not attenuate acute-phase disease in
      a macaque model of HIV infection.
AB  - Human pegivirus (HPgV) protects HIV+ people from HIV-associated disease, but the
      mechanism of this protective effect remains poorly understood. We sequentially
      infected cynomolgus macaques with simian pegivirus (SPgV) and simian
      immunodeficiency virus (SIV) to model HIV+HPgV co-infection. SPgV had no effect
      on acute-phase SIV pathogenesis-as measured by SIV viral load, CD4+ T cell
      destruction, immune activation, or adaptive immune responses-suggesting that
      HPgV's protective effect is exerted primarily during the chronic phase of HIV
      infection. We also examined the immune response to SPgV in unprecedented detail,
      and found that this virus elicits virtually no activation of the immune system
      despite persistently high titers in the blood over long periods of time. Overall,
      this study expands our understanding of the pegiviruses-an understudied group of
      viruses with a high prevalence in the global human population-and suggests that
      the protective effect observed in HIV+HPgV co-infected people occurs primarily
      during the chronic phase of HIV infection.

PMID- 29073260
TI  - Etanercept for steroid-refractory acute graft-versus-host disease: A single
      center experience.
AB  - BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication
      of allogeneic stem cell transplantation (alloSCT). High dose
      glucocorticosteroids, are currently recommended as first-line treatment for grade
      II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients.
      No standard second-line regimen has been established. Different options have been
      reported, including anti-TNFalpha antibodies. METHODS: We retrospectively
      reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated
      with etanercept at our institution. Patients were transplanted for a
      hematological malignancy and received either a myeloablative or a non
      myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin
      A and mycophenolic acid. RESULTS: Acute GVHD was diagnosed at a median of 61 days
      post-transplantation. All patients had grade III aGVHD of the gut. Second-line
      treatment with etanercept was started at a median of 13 days after initiation of
      first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR
      in 5 patients. Median overall survival after initiation of treatment with
      etanercept was 66 days (range 5-267) for the entire group. Median overall
      survival was 99 days (range 47-267 days) for responders and 17 days (range 5-66
      days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of
      death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%),
      cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). CONCLUSION:
      Second-line treatment with etanercept does induce responses in SR-aGVHD of the
      gut but appears to be associated with poor long-term survival even in responding
      patients.

PMID- 29073261
TI  - Difference in patterns of retinal ganglion cell damage between primary open-angle
      glaucoma and non-arteritic anterior ischaemic optic neuropathy.
AB  - PURPOSE: To compare the patterns of retinal ganglion cell damage between primary
      open-angle glaucoma (POAG) and non-arteritic anterior ischaemic optic neuropathy
      (NAION). METHODS: In total, 35 eyes with unilateral NAION, and 70 age- and
      average peripapillary retinal nerve fibre layer (RNFL) thickness-matched eyes
      with POAG, were enrolled as disease groups; 35 unaffected fellow eyes of the
      NAION, and 70 age- and refractive error-matched normal subjects for the POAG,
      were enrolled as their control groups, respectively. The peripapillary RNFL
      thickness and macular ganglion cell plus inner plexiform layer (GCIPL) thickness
      were compared between the disease groups and their controls, and between the two
      disease groups. RESULTS: Mean RNFL thicknesses at the 1 and 2 o'clock
      (superonasal) positions were thinner in NAION than in POAG (both p < 0.05). Mean
      RNFL thickness at 7 o'clock (inferotemporal) was thinner in POAG than in NAION (p
      = 0.001). Although there was no significant difference between NAION and POAG in
      average GCIPL thickness, all of the sectoral GCIPL thicknesses were thinner in
      NAION (all p < 0.05), except in the inferior and inferotemporal sectors. The
      ranges of the clock-hour RNFL with damage greater than the average RNFL thickness
      reduction, versus fellow eyes and control eyes, were 7 hours in NAION and 4 hours
      in POAG. CONCLUSIONS: The more damaged clock-hour RNFL regions differed between
      NAION (1 and 2 o'clock) and POAG (7 o'clock). Most sectoral GCIPL thicknesses
      were thinner in NAION than in POAG.

PMID- 29073262
TI  - Development and validation of immune dysfunction score to predict 28-day
      mortality of sepsis patients.
AB  - BACKGROUND: Sepsis-induced immune dysfunction ranging from cytokines storm to
      immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better
      risk stratification and mortality prediction and is mandatory before widely
      application of immunoadjuvant therapies. We aimed to develop and validate a
      scoring system according to patients' immune dysfunction status for 28-day
      mortality prediction. METHODS: A prospective observational study from a cohort of
      adult sepsis patients admitted to ICU between August 2013 and June 2016 at
      Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated immune dysfunction
      status through measurement of baseline plasma Cytokine levels, Monocyte human
      leukocyte-DR expression by flow cytometry, and stimulated immune response using
      post LPS stimulated cytokine elevation ratio. An immune dysfunction score was
      created for 28-day mortality prediction and was validated. RESULTS: A total of
      151 patients were enrolled. Data of the first consecutive 106 septic patients
      comprised the training cohort, and of other 45 patients comprised the validation
      cohort. Among the 106 patients, 21 died and 85 were still alive on day 28 after
      ICU admission. (mortality rate, 19.8%). Independent predictive factors revealed
      via multivariate logistic regression analysis included segmented neutrophil-to
      monocyte ratio, granulocyte-colony stimulating factor, interleukin-10, and
      monocyte human leukocyte antigen-antigen D-related levels, all of which were
      selected to construct the score, which predicted 28-day mortality with area under
      the curve of 0.853 and 0.789 in the training and validation cohorts,
      respectively. CONCLUSIONS: The immune dysfunction scoring system developed here
      included plasma granulocyte-colony stimulating factor level, interleukin-10
      level, serum segmented neutrophil-to-monocyte ratio, and monocyte human leukocyte
      antigen-antigen D-related expression appears valid and reproducible for
      predicting 28-day mortality.

PMID- 29073263
TI  - Silencing of G0/G1 switch gene 2 in cutaneous squamous cell carcinoma.
AB  - BACKGROUND: Methylation of a CpG island (CGI; a dense cluster of CpGs) located in
      the 5' region of a gene suppresses that gene's transcription. The expression of
      G0/G1 switch gene 2 (G0S2) is potentially associated with tumorigenesis. The aim
      of this study is to elucidate the methylation status of the CGI located in the 5'
      region of G0S2 (hereinafter called 5' G0S2 CGI) in cutaneous squamous cell
      carcinoma (SCC). METHODS: Quantitative real-time methylation-specific PCR (RT
      MSP) and bisulfite sequencing were performed to evaluate the methylation statuses
      of cutaneous SCC and normal epithelial cell samples. Quantitative real-time
      reverse transcription-PCR was performed to evaluate RNA expression levels.
      Immunohistochemical analysis was performed to detect protein expression. RESULTS:
      G0S2 was suppressed in the five SCC cell lines with 5' G0S2 CGI methylation
      levels of nearly 100.0% and was expressed in the two normal cultured
      keratinocytes with methylation levels of almost 0.0%. G0S2 was re-expressed in
      SCC cell lines treated with a demethylating agent. The in vivo methylation levels
      of 5' G0S2 CGI as determined by RT-MSP varied widely (0.0% to 77.7%) in 17
      cutaneous SCC samples and narrowly (0.1% to 7.3%) in 6 normal epidermis samples.
      Nine cutaneous SCC samples exhibited higher methylation levels than the highest
      methylation level (7.3%) of the 6 normal epidermis samples. Bisulfite sequencing
      showed dense methylated CpG sites within 5' G0S2 CGI in these highly methylated
      cutaneous SCC samples. The methylation levels of the cutaneous SCC samples did
      not correlate with any clinical parameters investigated or with histopathological
      grading. CONCLUSIONS: G0S2 is silenced by aberrant DNA methylation in a subset of
      cutaneous SCCs.

PMID- 29073264
TI  - Shelph2, a bacterial-like phosphatase of the malaria parasite Plasmodium
      falciparum, is dispensable during asexual blood stage.
AB  - During the erythrocytic cycle of the malaria parasite Plasmodium falciparum,
      egress and invasion are essential steps finely controlled by reversible
      phosphorylation. In contrast to the growing number of kinases identified as key
      regulators, phosphatases have been poorly studied, and calcineurin is the only
      one identified so far to play a role in invasion. PfShelph2, a bacterial-like
      phosphatase, is a promising candidate to participate in the invasion process, as
      it was reported to be expressed late during the asexual blood stage and to reside
      within an apical compartment, yet distinct from rhoptry bulb, micronemes, or
      dense granules. It was also proposed to play a role in the control of the red
      blood cell membrane deformability at the end of the invasion process. However,
      genetic studies are still lacking to support this hypothesis. Here, we take
      advantage of the CRISPR-Cas9 technology to tag shelph2 genomic locus while
      retaining its endogenous regulatory regions. This new strain allows us to follow
      the endogenous PfShelph2 protein expression and location during asexual blood
      stages. We show that PfShelph2 apical location is also distinct from the rhoptry
      neck or exonemes. We further demonstrate PfShelph2 dispensability during the
      asexual blood stage by generating PfShelph2-KO parasites using CRISPR-Cas9
      machinery. Analyses of the mutant during the course of the erythrocytic
      development indicate that there are no detectable phenotypic consequences of
      Pfshelph2 genomic deletion. As this lack of phenotype might be due to functional
      redundancy, we also explore the likelihood of PfShelph1 (PfShelph2 paralog) being
      a compensatory phosphatase. We conclude that despite its cyclic expression
      profile, PfShelph2 is a dispensable phosphatase during the Plasmodium falciparum
      asexual blood stage, whose function is unlikely substituted by PfShelph1.

PMID- 29073265
TI  - MiRNA-124 is a link between measles virus persistent infection and cell division
      of human neuroblastoma cells.
AB  - Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral
      organs. However, in rare cases, the virus can persistently infect cells within
      the central nervous system. Although some of the factors that allow MV to persist
      are known, the contribution of host cell-encoded microRNAs (miRNA) have not been
      described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all
      multicellular organisms and some viruses, which regulate gene expression in a
      sequence-specific manner. We have studied the contribution of host cell-encoded
      miRNAs to the establishment of MV persistent infection in human neuroblastoma
      cells. Persistent MV infection was accompanied by differences in the expression
      profile and levels of several host cell-encoded microRNAs as compared to
      uninfected cells. MV persistence infection of a human neuroblastoma cell line
      (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin
      dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell
      division but not cell death. By contrast, acute MV infection of UKF-NB cells did
      not result in increased miRNA-124 levels or CDK6 reduction. Ectopic
      overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells,
      causing cell death; implying that miRNA-124 over expression can sensitize cells
      to death only in the presence of MV persistent infection. To determine if miRNA
      124 directly contributes to the establishment of MV persistence, UKF-NB cells
      overexpressing miRNA-124 were acutely infected, resulting in establishment of
      persistently infected colonies. We propose that miRNA-124 triggers a CDK6
      dependent decrease in cell proliferation, which facilitates the establishment of
      MV persistence in neuroblastoma cells. To our knowledge, this is the first report
      to describe the role of a specific miRNA in MV persistence.

PMID- 29073266
TI  - Effect of a short training on neonatal face-mask ventilation performance in a low
      resource setting.
AB  - BACKGROUND: We assessed whether a short training, effective in a high resource
      country, was able to improve the quality of face-mask ventilation (FMV) in a low
      resource setting. METHODS: Local healthcare providers at the Centre Medico
      Social, Kouve, Togo were asked to ventilate a neonatal leak-free manikin before
      (time-t1) and after (t2) a two-minute training session. Immediately after this
      section, a further two-minute training with participants aware of the data
      monitor was offered. Finally, a third 1-minute FMV round (t3) was performed by
      each participant. Ventilatory parameters were recorded using a computerized
      system. Primary outcome was the percentage of breaths with relevant mask leak
      (>25%). Secondary outcomes were percentages of breaths with a low peak
      inspiratory pressure (PIP<20 cm H2O), within the recommended PIP (20-35 cm H2O)
      and with a high PIP (>35 cm H2O). RESULTS: Twenty-six subjects participated in
      the study. The percentage of relevant mask leak significantly decreased
      (p<0.0001; beta = -0.76, SE = 0.10) from 89.7% (SD 21.5%) at t1 to 45.4% (SD
      27.2%) at t2 and to 18.3% (SD 20.1%) at t3. The percentage of breaths within the
      recommended PIP significantly increased (p<0.0001; beta = +0.54, SE = 0.12). The
      percentage of breaths with PIP>35 cm H2O was 19.5% (SD 32.8%) at t1 and 39.2% (SD
      37.7%) at t2 (padj = 0.27; beta = +0.61, SE = 0.36) and significantly decreased
      (padj = 0.01; beta = -1.61, SE = 0.55) to 6.0% (SD 15.4%) at t3. CONCLUSIONS: A 2
      minute training on FMV, effective in a high resource country, had a positive
      effect also in a low resource setting. FMV performance further improved after an
      extra 2-minute verbal recall plus real time feedback. Although the training was
      extended, it still does not cost much time and effort. Further studies are needed
      to establish if these basic skills are transferred in real patients and if they
      are maintained over time.

PMID- 29073269
TI  - Nasal carriage rate and antibiotic susceptibility pattern of Neisseria
      meningitidis in healthy Ethiopian children and adolescents: A cross-sectional
      study.
AB  - BACKGROUND: Community nasal meningococcal carriage rates are high across Africa.
      Meningococcal infections are major causes of morbidity and mortality in the
      continent; especially among children and adolescents. This study aimed to
      determine the prevalence of nasal carriage and antibiotic susceptibilities of
      meningococcal isolates from healthy Ethiopian children and adolescents. METHOD: A
      cross-sectional study was conducted in one of the sub-cities of Addis Ababa,
      Ethiopia. Nasal swabs were collected and processed for identification,
      serogrouping and testing susceptibilities for three antibiotics using standard
      microbiological techniques. Data on epidemiologic risk factors were collected
      using a structured questionnaire and the magnitude of their association with
      carriage was assessed using bivariate and multivariate analysis. RESULT: A total
      of 240 samples were collected (115 from males and 125 from females). The mean age
      of study participants was 11.1 years. The prevalence of nasal carriage for
      Neisseria meningitidis was 20.4% (49/240). Carriage was significantly higher
      among children living under crowded conditions (OR 1.268; 95% CI: 1.186-1.355; p
      = 0.006). The predominant serogroups were W135-20/49 isolates (40.8%) and C-12/49
      isolates (24.5%) and 83.7% of meningococci were sensitive for Ciprofloxacin. In
      contrast, isolates showed high resistance to Ceftriaxone (69.4%) while only 4.2%
      were sensitive for Penicillin. Multi-drug resistance was documented for 14.3% of
      the isolates. CONCLUSIONS: Meningococcal carriage rate was found to be high with
      higher rates associated with children and adolescents living in crowded living
      conditions. Predominant isolates were of serogroup W135 and C and the isolates
      showed marked susceptibility to Ciprofloxacin and resistance to Ceftriaxone and
      Penicillin.

PMID- 29073267
TI  - Comparative genomics of geographically distant Fusarium fujikuroi isolates
      revealed two distinct pathotypes correlating with secondary metabolite profiles.
AB  - Fusarium fujikuroi causes bakanae ("foolish seedling") disease of rice which is
      characterized by hyper-elongation of seedlings resulting from production of
      gibberellic acids (GAs) by the fungus. This plant pathogen is also known for
      production of harmful mycotoxins, such as fusarins, fusaric acid, apicidin F and
      beauvericin. Recently, we generated the first de novo genome sequence of F.
      fujikuroi strain IMI 58289 combined with extensive transcriptional, epigenetic,
      proteomic and chemical product analyses. GA production was shown to provide a
      selective advantage during infection of the preferred host plant rice. Here, we
      provide genome sequences of eight additional F. fujikuroi isolates from distant
      geographic regions. The isolates differ in the size of chromosomes, most likely
      due to variability of subtelomeric regions, the type of asexual spores
      (microconidia and/or macroconidia), and the number and expression of secondary
      metabolite gene clusters. Whilst most of the isolates caused the typical bakanae
      symptoms, one isolate, B14, caused stunting and early withering of infected
      seedlings. In contrast to the other isolates, B14 produced no GAs but high
      amounts of fumonisins during infection on rice. Furthermore, it differed from the
      other isolates by the presence of three additional polyketide synthase (PKS)
      genes (PKS40, PKS43, PKS51) and the absence of the F. fujikuroi-specific apicidin
      F (NRPS31) gene cluster. Analysis of additional field isolates confirmed the
      strong correlation between the pathotype (bakanae or stunting/withering), and the
      ability to produce either GAs or fumonisins. Deletion of the fumonisin and
      fusaric acid-specific PKS genes in B14 reduced the stunting/withering symptoms,
      whereas deletion of the PKS51 gene resulted in elevated symptom development.
      Phylogenetic analyses revealed two subclades of F. fujikuroi strains according to
      their pathotype and secondary metabolite profiles.

PMID- 29073268
TI  - Compartmented neuronal cultures reveal two distinct mechanisms for alpha
      herpesvirus escape from genome silencing.
AB  - Alpha herpesvirus genomes encode the capacity to establish quiescent infections
      (i.e. latency) in the peripheral nervous system for the life of their hosts.
      Multiple times during latency, viral genomes can reactivate to start a productive
      infection, enabling spread of progeny virions to other hosts. Replication of
      alpha herpesviruses is well studied in cultured cells and many aspects of
      productive replication have been identified. However, many questions remain
      concerning how a productive or a quiescent infection is established. While
      infections in vivo often result in latency, infections of dissociated neuronal
      cultures in vitro result in a productive infection unless lytic viral replication
      is suppressed by DNA polymerase inhibitors or interferon. Using primary
      peripheral nervous system neurons cultured in modified Campenot tri-chambers, we
      previously reported that reactivateable, quiescent infections by pseudorabies
      virus (PRV) can be established in the absence of any inhibitor. Such infections
      were established in cell bodies only when physically isolated axons were infected
      at a very low multiplicity of infection (MOI). In this report, we developed a
      complementation assay in compartmented neuronal cultures to investigate host and
      viral factors in cell bodies that prevent establishment of quiescent infection
      and promote productive replication of axonally delivered genomes (i.e. escape
      from silencing). Stimulating protein kinase A (PKA) signaling pathways in
      isolated cell bodies, or superinfecting cell bodies with either UV-inactivated
      PRV or viral light particles (LP) promoted escape from genome silencing and
      prevented establishment of quiescent infection but with different molecular
      mechanisms. Activation of PKA in cell bodies triggers a slow escape from
      silencing in a cJun N-terminal kinase (JNK) dependent manner. However, escape
      from silencing is induced rapidly by infection with UVPRV or LP in a PKA- and JNK
      independent manner. We suggest that viral tegument proteins delivered to cell
      bodies engage multiple signaling pathways that block silencing of viral genomes
      delivered by low MOI axonal infection.

PMID- 29073270
TI  - The immune battlefield: The impact of inflammatory cytokines on CD8+ T-cell
      immunity.

PMID- 29073271
TI  - Lower incidence of fracture after IV bisphosphonates in girls with Rett syndrome
      and severe bone fragility.
AB  - BACKGROUND: Classic Rett Syndrome (RS) is a disabling condition mainly caused by
      MECP2 mutations. Girls with RS are at risk of developing bone fragility and
      fractures at a young age which results in pain and may seriously impair quality
      of life. OBJECTIVE: To retrospectively assess the safety and efficacy of IV
      bisphosphonates on fracture, bone mineral density (BMD) and bone markers in RS
      girls with bone fragility. METHODS: RS girls received either IV pamidronate (n =
      19) or IV zoledronate (n = 1) for 2 years. RESULTS: Of 20 patients studied (age:
      12.5 years [6; 39]), 14 were non-ambulatory. The incidence of fracture decreased
      from 37 fractures in 20 patients, to 1 fracture during or after treatment (follow
      up: 3.1 years [1.5; 5]). The spine BMD Z-score improved from -3.2 [-5.6; -0.1] to
      -2.2 [-3.8; 0.0], p = 0.0006. Most parents reported decreases in chronic pain and
      2 patients started to walk. Urinary calcium excretion decreased from 0.7 [0.18;
      1.5] to 0.2 [0.03; 0.67] mM/mM of creatinine (p = 0.0001). Pamidronate was well
      tolerated. CONCLUSION: RS girls should be screened for impaired bone
      mineralization and preventive measures should be taken. In girls experiencing
      fractures, IV bisphosphonates constitute a beneficial adjuvant treatment to
      diminish the risk of fracture and restore bone density.

PMID- 29073272
TI  - Highly aggressive rat prostate tumors rapidly precondition regional lymph nodes
      for subsequent metastatic growth.
AB  - The aim of this study was to examine in what ways MatLyLu (MLL) rat prostate
      tumors with high metastatic capacity influence regional lymph nodes prior to
      metastatic establishment compared to AT1 rat prostate tumors with low metastatic
      potential. MLL or AT1 tumor cells were injected into the ventral prostate of
      immunocompetent rats. Tumor and lymph node morphology, and lymph node mRNA
      expression of macrophage associated markers, T-cell associated markers, and
      cytokines were examined over time until the first microscopic signs of metastases
      (at day 14 for MLL- and at day 28 for AT1-tumors). Already at day 3 after tumor
      cell injection, when the tumors were extremely small and occupied less than 1% of
      the prostate volume, MLL- and AT1-tumors provoked different immune responses in
      both the prostate and the regional lymph nodes. MLL-tumors induced expression of
      immunosuppressive cytokines, suppressed T-cell accumulation, and directed T-cells
      towards an immunosuppressive phenotype. AT1-tumors caused a response more similar
      to that in vehicle-injected animals, with accumulation of T-cells in tumors and
      regional lymph nodes. Prostate tumors with high metastatic potential were able to
      precondition regional lymph nodes to subsequent metastatic growth in ways
      different from tumors with less metastatic potential. This may indicate the
      existence of a time-window when pre-metastatic changes in regional lymph nodes
      can aid in the prognostication of locally aggressive and potentially metastatic
      prostate cancer.

PMID- 29073273
TI  - The level of performance stabilization influences motor adaptation on an
      isometric force control task.
AB  - This study compared the effects of two levels of performance stabilization on the
      adaptation to unpredictable perturbations in an isometric control force task with
      the goal of controlling 40% of the maximum force. The experiment consisted of pre
      exposure and exposure phases. In the pre-exposure two levels of performance
      stabilization were manipulated: a stabilization group (SG) performed three trials
      in a row while maintaining 40% of the maximum force for three seconds and an
      absolute error less than or equal to 5% (i.e., the criteria of performance), and
      a superstabilization group (SSG) performed six blocks of the same criteria.
      During the exposure phase, the task was the same as that in the pre-exposure
      phase; however, it was inserted 9 trials of perturbations when the task goal
      changed to 60% of the maximum force. We measured the %RMSE, RMS from the biceps
      and triceps brachii and co-contraction. In the pre-exposure phase, both groups
      showed similar performance and muscle activity. When exposed to the
      perturbations, SSG performance more quickly returned to the previous level of
      accuracy, showed lower muscle activation and demonstrated a greater muscle co
      contraction than did SG. The results give support to the adaptive process model
      on motor learning.

PMID- 29073274
TI  - Transcriptome analysis of mRNA and microRNAs in intramuscular fat tissues of
      castrated and intact male Chinese Qinchuan cattle.
AB  - Intramuscular fat (IMF) is known to enhance beef palatability and can be markedly
      increased by castration. However, there is little understanding of the molecular
      mechanism underlying the IMF deposition after castration of beef cattle. We
      hypothesize that genetic regulators function differently in IMF from bulls and
      steers. Therefore, after detecting serum testosterone and lipid parameter, as
      well as the contents of IMF at 6, 12, 18 and 24 months, we have investigated
      differentially expressed (DE) microRNAs (miRNAs) and mRNAs in IMF of bulls and
      steers at 24 months of age in Qinchuan cattle using next-generation sequencing,
      and then explored the possible biopathways regulating IMF deposition. Serum
      testosterone levels were significantly decreased in steers, whereas IMF content,
      serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and
      triglycerides (TGs) were markedly increased in steers. Comparing the results of
      steers and bulls, 580 upregulated genes and 1,120 downregulated genes in IMF
      tissues were identified as DE genes correlated with IMF deposition. The
      upregulated genes were mainly associated with lipid metabolism, lipogenesis and
      fatty acid transportation signalling pathways, and the downregulated genes were
      correlated with immune response and intracellular signal transduction.
      Concurrently, the DE miRNAs-important players in adipose tissue accumulation
      induced by castration-were also examined in IMF tissues; 52 DE miRNAs were
      identified. The expression profiles of selected genes and miRNAs were also
      confirmed by quantitative real-time PCR (qRT-PCR) assays. Using integrated
      analysis, we constructed the microRNA-target regulatory network which was
      supported by target validation using the dual luciferase reporter system.
      Moreover, Ingenuity Pathway Analysis (IPA) software was used to construct a
      molecular interaction network that could be involved in regulating IMF after
      castration. The detected molecular network is closely associated with lipid
      metabolism and adipocyte differentiation, which is supported by functional
      identification results of bta-let-7i on bovine preadipocytes. These results
      provided valuable insights into the molecular mechanisms of the IMF phenotype
      differences between steers and bulls.

PMID- 29073275
TI  - Thrombosis after liver transplantation for hepatocellular carcinoma.
AB  - The influence of thrombosis on the prognosis of patients with hepatocellular
      carcinoma (HCC) after liver transplantation (LT) and the role of the commonest
      inherited thrombophilia abnormalities factor V Leiden and prothrombin G20210A in
      the development of thrombosis are unknown. We investigated a cohort of patients
      who underwent LT for HCC with the aim to estimate the incidence rate (IR) of
      thrombosis, its influence on mortality and re-transplantation rates and, in the
      frame of a nested case-control study, the role of thrombophilia in donors and
      recipients for the development of thrombosis. Four-hundred and thirty patients
      underwent LT and were followed for a median of 7.2 years. Twenty-six recipients
      (6%) developed thrombosis (IR 1.06 [95%CI: 0.71-1.53] per 100 pts-yr). Mortality
      rate after LT was 3.95 (95%CI: 3.22-4.79) per 100 pts-yr and was not influenced
      by thrombosis. Re-transplantation was planned for 33 patients and was more common
      in patients with thrombosis than in those without (HR 2.50 [95%CI: 0.87-7.17]).
      The risk of thrombosis was 4 times higher in recipients with thrombophilia than
      in those without (OR 4.23 [95%CI: 0.99-18.04]) and 6 times higher when the
      analysis was restricted to venous thrombosis (OR 6.26 [95%CI: 1.19-32.85]). The
      presence of inherited thrombophilia in the donors did not increase the risk of
      thrombosis of the recipient. In conclusion, thrombosis is a complication of 6% of
      patients transplanted for HCC and increases the risk of re-transplantation but
      not of mortality. The risk of thrombosis, particularly venous, is increased in
      the presence of thrombophilia abnormalities in the recipients.

PMID- 29073276
TI  - Riboproteomics: A versatile approach for the identification of host protein
      interaction network in plant pathogenic noncoding RNAs.
AB  - Pathogenic or non-pathogenic small (17 to 30 nt) and long (>200 nt) non-coding
      RNAs (ncRNAs) have been implicated in the regulation of gene expression at
      transcriptional, post-transcriptional and epigenetic level by interacting with
      host proteins. However, lack of suitable experimental system precludes the
      identification and evaluation of the functional significance of host proteins
      interacting with ncRNAs. In this study, we present a first report on the
      application of riboproteomics to identify host proteins interacting with small,
      highly pathogenic, noncoding satellite RNA (sat-RNA) associated with Cucumber
      mosaic virus, the helper virus (HV). RNA affinity beads containing sat-RNA
      transcripts of (+) or (-)-sense covalently coupled to cyanogen bromide activated
      sepharose beads were incubated with total protein extracts from either healthy or
      HV-infected Nicotiana benthamiana leaves. RNA-protein complexes bound to the
      beads were eluted and subjected to MudPIT analysis. Bioinformatics programs
      PANTHER classification and WoLF-PSORT were used to further classify the
      identified host proteins in each case based on their functionality and
      subcellular distribution. Finally, we observed that the host protein network
      interacting with plus and minus-strand transcripts of sat-RNA, in the presence or
      absence of HV is distinct, and the global interactome of host proteins
      interacting with satRNA in either of the orientations is very different.

PMID- 29073277
TI  - Isolation, purification and characterization of 5'-phosphodiesterase from
      Aspergillus fumigatus.
AB  - 5'-Phosphodiesterase (5'-PDE) catalyzes the hydrolysis of ribonucleic acid to
      obtain a mixture of ribonucleotides, such as 5'-guanosine monophosphate and 5'
      adenosine monophosphate. In this study, a 5'-PDE was newly isolated and purified
      from Aspergillus fumigatus. Following purification, this enzyme exhibited a
      specific activity of 1036.76 U/mg protein, a molecular weight of 9.5 kDa, and an
      optimal temperature and pH for enzyme activity of 60 degrees C and 5.0,
      respectively. However, its activity was partially inhibited by Fe3+, Cu2+, and
      Zn2+, but slightly improved by the presence of K+ and Na+. Additionally, chemical
      modification experiments were also applied to investigate the structural
      information of 5'-PDE, in which the residues containing carboxyl and imidazole
      groups were essential for enzyme activity based on their localization in the 5'
      PDE active site. Furthermore, purified 5'-PDE could specifically catalyze the
      synthesis of ribonucleotides with a Vmax 0.71 mmol/mg.min and a KM of 13.60
      mg/mL.

PMID- 29073278
TI  - Soil phosphorus functional fractions and tree tissue nutrient concentrations
      influenced by stand density in subtropical Chinese fir plantation forests.
AB  - Stand density regulation is an important measure of plantation forest management,
      and phosphorus (P) is often the limiting factor of tree productivity, especially
      in the subtropics and tropics. However, the stand density influence on ecosystem
      P cycling is unclear in Chinese fir (Cunninghamia lanceolata) plantations of
      subtropical China. We collected rhizosphere and bulk soils, leaves and twigs with
      different ages and roots with different orders to measure P and nitrogen (N)
      variables in Chinese fir plantations with low density (LDCF) and high density
      (HDCF) at Fujian and Hunan provinces of subtropical China. Rhizosphere soil
      labile P, slow P, occluded P and extractable P were higher in LDCF than HDCF at
      two sites. Meanwhile, P and N concentrations of 1-year-old leaves and twigs were
      higher in LDCF than HDCF and leaf N/P ratio generally increased with increasing
      leaf age at two sites. Rhizosphere vs. bulk soil labile P and occluded P were
      greater in LDCF than HDCF at Fujian. Nitrogen resorption efficiencies (NRE) of
      leaves and twigs were higher in LDCF than HDCF at Fujian, while their P
      resorption efficiencies (PRE) were not different between two densities at two
      sites. The average NRE of leaves (41.7%) and twigs (65.6%) were lower than the
      corresponding PRE (67.8% and 78.0%, respectively). Our results suggest that
      reducing stem density in Chinese fir plantations might be helpful to increase
      soil active P supplies and meet tree nutrient requirements.

PMID- 29073279
TI  - Open source machine-learning algorithms for the prediction of optimal cancer drug
      therapies.
AB  - Precision medicine is a rapidly growing area of modern medical science and open
      source machine-learning codes promise to be a critical component for the
      successful development of standardized and automated analysis of patient data.
      One important goal of precision cancer medicine is the accurate prediction of
      optimal drug therapies from the genomic profiles of individual patient tumors. We
      introduce here an open source software platform that employs a highly versatile
      support vector machine (SVM) algorithm combined with a standard recursive feature
      elimination (RFE) approach to predict personalized drug responses from gene
      expression profiles. Drug specific models were built using gene expression and
      drug response data from the National Cancer Institute panel of 60 human cancer
      cell lines (NCI-60). The models are highly accurate in predicting the drug
      responsiveness of a variety of cancer cell lines including those comprising the
      recent NCI-DREAM Challenge. We demonstrate that predictive accuracy is optimized
      when the learning dataset utilizes all probe-set expression values from a
      diversity of cancer cell types without pre-filtering for genes generally
      considered to be "drivers" of cancer onset/progression. Application of our models
      to publically available ovarian cancer (OC) patient gene expression datasets
      generated predictions consistent with observed responses previously reported in
      the literature. By making our algorithm "open source", we hope to facilitate its
      testing in a variety of cancer types and contexts leading to community-driven
      improvements and refinements in subsequent applications.

PMID- 29073280
TI  - Pea Marker Database (PMD) - A new online database combining known pea (Pisum
      sativum L.) gene-based markers.
AB  - Pea (Pisum sativum L.) is the oldest model object of plant genetics and one of
      the most agriculturally important legumes in the world. Since the pea genome has
      not been sequenced yet, identification of genes responsible for mutant phenotypes
      or desirable agricultural traits is usually performed via genetic mapping
      followed by candidate gene search. Such mapping is best carried out using gene
      based molecular markers, as it opens the possibility for exploiting genome
      synteny between pea and its close relative Medicago truncatula Gaertn.,
      possessing sequenced and annotated genome. In the last 5 years, a large number of
      pea gene-based molecular markers have been designed and mapped owing to the rapid
      evolution of "next-generation sequencing" technologies. However, the access to
      the complete set of markers designed worldwide is limited because the data are
      not uniformed and therefore hard to use. The Pea Marker Database was designed to
      combine the information about pea markers in a form of user-friendly and
      practical online tool. Version 1 (PMD1) comprises information about 2484 genic
      markers, including their locations in linkage groups, the sequences of
      corresponding pea transcripts and the names of related genes in M. truncatula.
      Version 2 (PMD2) is an updated version comprising 15944 pea markers in the same
      format with several advanced features. To test the performance of the PMD, fine
      mapping of pea symbiotic genes Sym13 and Sym27 in linkage groups VII and V,
      respectively, was carried out. The results of mapping allowed us to propose the
      Sen1 gene (a homologue of SEN1 gene of Lotus japonicus (Regel) K. Larsen) as the
      best candidate gene for Sym13, and to narrow the list of possible candidate genes
      for Sym27 to ten, thus proving PMD to be useful for pea gene mapping and cloning.
      All information contained in PMD1 and PMD2 is available at
      www.peamarker.arriam.ru.

PMID- 29073281
TI  - Green tea polyphenols alter lipid metabolism in the livers of broiler chickens
      through increased phosphorylation of AMP-activated protein kinase.
AB  - Our previous results showed that green tea polyphenols (GTPs) significantly
      altered the expression of lipid-metabolizing genes in the liver of chickens.
      However, the underlying mechanism was not elucidated. In this study, we further
      characterized how GTPs influence AMP-activated protein kinase (AMPK) in the
      regulation of hepatic fat metabolism. Thirty-six male chickens were fed GTPs at a
      daily dose of 0, 80 or 160 mg/kg of body weight for 4 weeks. The results
      demonstrated that oral administration of GTPs significantly reduced hepatic lipid
      content and abdominal fat mass, enhanced the phosphorylation levels of AMPKalpha
      and ACACA, and altered the mRNA levels and enzymatic activities of lipid
      metabolizing enzymes in the liver. These results suggested that the activation of
      AMPK is a potential mechanism by which GTPs regulate hepatic lipid metabolism in
      such a way that lipid synthesis is reduced and fat oxidation is stimulated.

PMID- 29073282
TI  - Cardiovascular phenotype in Smad3 deficient mice with renovascular hypertension.
AB  - Renovascular hypertension (RVH) has deleterious effects on both the kidney and
      the heart. TGF-beta signaling through Smad3 directs tissue fibrosis in chronic
      injury models. In the 2-kidney 1-clip (2K1C) model of RVH, employing mice on the
      129 genetic background, Smad3 deficiency (KO) protects the stenotic kidney (STK)
      from development of interstitial fibrosis. However, these mice have an increased
      incidence of sudden cardiac death following 2K1C surgery. The purpose of this
      study was to characterize the cardiovascular phenotype of these mice. Renal
      artery stenosis (RAS) was established in Wild-type (WT) and Smad3 KO mice (129
      genetic background) by placement of a polytetrafluoroethylene cuff on the right
      renal artery. Mortality was 25.5% for KO mice with RAS, 4.1% for KO sham mice,
      1.2% for WT with RAS, and 1.8% for WT sham mice. Myocardial tissue of mice
      studied at 3 days following surgery showed extensive myocyte necrosis in KO but
      not WT mice. Myocyte necrosis was associated with a rapid induction of Ccl2
      expression, macrophage influx, and increased MMP-9 activity. At later time
      points, both KO and WT mice developed myocardial fibrosis. No aortic aneurysms or
      dissections were observed at any time point. Smad3 KO mice were backcrossed to
      the C57BL/6J strain and subjected to RAS. Sudden death was observed at 10-14 days
      following surgery in 62.5% of mice; necropsy revealed aortic dissections as the
      cause of death. As observed in the 129 mice, the STK of Smad3 KO mice on the
      C57BL/6J background did not develop significant chronic renal damage. We conclude
      that the cardiovascular manifestations of Smad3 deficient mice are strain
      specific, with myocyte necrosis in 129 mice and aortic rupture in C57BL/6J mice.
      Future studies will define mechanisms underlying this strain-specific effect on
      the cardiovascular system.

PMID- 29073284
TI  - Correction: FRIZZLED7 Is Required for Tumor Inititation and Metastatic Growth of
      Melanoma Cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0147638.].

PMID- 29073283
TI  - Identification of novel substrates of Shigella T3SA through analysis of its
      virulence plasmid-encoded secretome.
AB  - Many human Gram-negative bacterial pathogens express a Type Three Secretion
      Apparatus (T3SA), including among the most notorious Shigella spp., Salmonella
      enterica, Yersinia enterocolitica and enteropathogenic Escherichia coli (EPEC).
      These bacteria express on their surface multiple copies of the T3SA that mediate
      the delivery into host cells of specific protein substrates critical to
      pathogenesis. Shigella spp. are Gram-negative bacterial pathogens responsible for
      human bacillary dysentery. The effector function of several Shigella T3SA
      substrates has largely been studied but their potential cellular targets are far
      from having been comprehensively delineated. In addition, it is likely that some
      T3SA substrates have escaped scrutiny as yet. Indeed, sequencing of the virulence
      plasmid of Shigella flexneri has revealed numerous open reading frames with
      unknown functions that could encode additional T3SA substrates. Taking advantage
      of label-free mass spectrometry detection of proteins secreted by a
      constitutively secreting strain of S. flexneri, we identified five novel
      substrates of the T3SA. We further confirmed their secretion through the T3SA and
      translocation into host cells using beta-lactamase assays. The coding sequences
      of two of these novel T3SA substrates (Orf13 and Orf131a) have a guanine-cytosine
      content comparable to those of T3SA components and effectors. The three other
      T3SA substrates identified (Orf48, Orf86 and Orf176) have significant homology
      with antitoxin moieties of type II Toxin-Antitoxin systems usually implicated in
      the maintenance of low copy plasmids. While Orf13 and Orf131a might constitute
      new virulence effectors contributing to S. flexneri pathogenicity, potential
      roles for the translocation into host cells of antitoxins or antitoxin-like
      proteins during Shigella infection are discussed.

PMID- 29073285
TI  - Correction: Worldwide trends in volume and quality of published protocols of
      randomized controlled trials.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173042.].

PMID- 29073286
TI  - Differential adipokine receptor expression on circulating leukocyte subsets in
      lean and obese children.
AB  - BACKGROUND: Childhood obesity prevalence has increased worldwide and is an
      important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD).
      The production of inflammatory adipokines by obese adipose tissue contributes to
      the development of T2D and CVD. While levels of circulating adipokines such as
      adiponectin and leptin have been established in obese children and adults, the
      expression of adiponectin and leptin receptors on circulating immune cells can
      modulate adipokine signalling, but has not been studied so far. Here, we aim to
      establish the expression of adiponectin and leptin receptors on circulating
      immune cells in obese children pre and post-lifestyle intervention compared to
      normal weight control children. METHODS: 13 obese children before and after a 1
      year lifestyle intervention were compared with an age and sex-matched normal
      weight control group of 15 children. Next to routine clinical and biochemical
      parameters, circulating adipokines were measured, and flow cytometric analysis of
      adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on
      peripheral blood mononuclear cell subsets was performed. RESULTS: Obese children
      exhibited typical clinical and biochemical characteristics compared to controls,
      including a higher BMI-SD, blood pressure and circulating leptin levels, combined
      with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle
      intervention resulted in stabilization of their BMI-SD. Overall, circulating
      leukocyte subsets showed distinct adipokine receptor expression profiles. While
      monocytes expressed high levels of all adipokine receptors, NK and iNKT cells
      predominantly expressed AdipoR2, and B-lymphocytes and CD4+ and CD8+ T-lymphocyte
      subsets expressed AdipoR2 as well as leptin receptor. Strikingly though,
      leukocyte subset numbers and adipokine receptor expression profiles were largely
      similar in obese children and controls. Obese children showed higher naive B-cell
      numbers, and pre-intervention also higher numbers of immature transition B-cells
      and intermediate CD14++CD16+ monocytes combined with lower total monocyte
      numbers, compared to controls. Furthermore, adiponectin receptor 1 expression on
      nonclassical CD14+CD16++ monocytes was consistently upregulated in obese children
      pre-intervention, compared to controls. However, none of the differences in
      leukocyte subset numbers and adipokine receptor expression profiles between obese
      children and controls remained significant after multiple testing correction.
      CONCLUSIONS: First, the distinct adipokine receptor profiles of circulating
      leukocyte subsets may partly explain the differential impact of adipokines on
      leukocyte subsets. Second, the similarities in adipokine receptor expression
      profiles between obese children and normal weight controls suggest that adipokine
      signaling in childhood obesity is primarily modulated by circulating adipokine
      levels, instead of adipokine receptor expression.

PMID- 29073287
TI  - Do fungi have an innate immune response? An NLR-based comparison to plant and
      animal immune systems.

PMID- 29073288
TI  - Complementary and alternative medicine in Brazilian children and adolescents with
      type 1 diabetes mellitus.
AB  - INTRODUCTION: Patients with type 1 diabetes mellitus (T1DM) resort to
      complementary and alternative medicine (CAM) for symptomatic relief, to inhibit
      progression or to reduce side effects associated with conventional therapy.
      OBJECTIVES: Build a profile and assess the prevalence of the use of CAM in
      Brazilian children and adolescents with T1DM under conventional treatment.
      METHODS: Cross-sectional study with interviews with the legal representatives of
      patients with T1DM (of both gender, aged 2- 17 years). The profile of users of
      CAM was built based on the percentage of patients that use or did not use CAM,
      frequency ratio and multiple correspondence analysis. RESULTS: Seventy patients
      (10.7 +/- 3.8 years, 34 girls and 36 boys) were assessed. Among them, 41.5% used
      CAM. Most of them (69%) did not inform their doctors on this use. The main
      reasons for the use of the CAM were the desire to improve blood sugar levels and
      cure the disease. The most widely used methods were medicinal plants,
      acupuncture, and prayer. Positive associations between the use of CAM and
      sociodemographic characteristics were also found. CONCLUSIONS: The construction
      of the profile revealed a group of patients that deserve a special attention by
      health professionals because they are more prone to adopt behaviors that impair
      the success of the treatment, such as not counting carbohydrates and not
      informing the doctor about the use of CAM.

PMID- 29073289
TI  - PM10 concentration and microbiological assessment of air in relation to the
      number of acute cases of type 1 diabetes mellitus in the Lubelskie Voivodeship.
      Preliminary report.
AB  - INTRODUCTION: The aim of our study was to evaluate the relation between the
      concentration of particulate matter of less than 10 MUm in diameter (PM10) in air
      and the effect of psychrophilic bacteria, mesophilic bacteria and mould fungi on
      the number of new cases of type 1 diabetes mellitus in children and adolescents
      in the Lubelskie Voivodeship in the years 2015-2016. PATIENTS AND METHODS:
      Epidemiological data on the number of new cases of T1DM was obtained from the
      Department of Paediatric Endocrinology and Diabetology of the Medical University
      in Lublin. The number of births for the year 2015 and 2016 in the Lublin
      Voivodeship was acquired from the statistical yearbook by the Polish Central
      Statistical Office (GUS). Data on PM10 concentration in the Lubelskie Voivodeship
      was obtained from the report and annual evaluations of air quality prepared by
      the Voivodeship Inspectorate of Environmental Protection (WIOS) in Lublin. The
      analysis of psychrophilic bacteria, mesophilic bacteria and mould fungi in air
      was performed with use of the impact method and an air sampler. RESULTS: In the
      years 2015-2016 in the Lubelskie Voivodeship the number of births was 39 381 and
      152 new cases of type 1 diabetes mellitus were recorded. The annual and 24-hour
      concentration of PM10 in air in 2015 was higher compared to 2016; however, the
      difference was not statistically significant. Moreover, we detected a higher
      number of psychrophilic bacteria 2739 vs 1000 CFU/m3 and a significantly higher
      number of mesophilic bacteria 92493 vs 1000 CFU/m3 than the norm specified in the
      Polish standard PN-89/Z-04111/02. A further analysis of air samples collected in
      the Lubelskie Voivodeship revealed lower a concentration of mould fungi compared
      to the Polish standard PN-89/Z-04111/02 (3840 vs 5000 CFU/m3, respectively). We
      isolated 9 types of mould fungi and 1 type of yeast-like fungus that are thought
      to have a negative effect on people's health. The statistical analysis revealed a
      relation between the number of new cases of T1DM and the number of psychrophilic
      bacteria (beta= 2.86; p<0.05), mesophilic bacteria (beta = 2.824; p<0.05) and the
      number of mould fungi (beta=2.923; p<0.001). The analysis of linear regression
      revealed a relation between the number of new T1DM cases and mean annual
      concentration of PM10 for the year 2016 (p<0.001). However, there was no relation
      observed between the number of new cases of T1DM and the mean annual
      concentration of PM10 in air in the Lubelskie Voivodeship in 2015. CONCLUSIONS:
      Our preliminary results confirm the not yet fully explored relation between air
      pollution and the risk of type 1 DM in children and adolescents.

PMID- 29073290
TI  - Nutritional status at the moment of diagnosis in childhood cancer patients.
AB  - INTRODUCTION: Children with a neoplastic disease are highly susceptible to
      malnutrition. The main objective of the study was to assess the frequency of
      undernourishment and obesity at the time of the diagnosis of the neoplastic
      disease at children. MATERIALS AND METHODS: The study included 734 patients (58%
      males) at the age 1-20,25, with the diagnosis of neoplasm in the years 1986-2014.
      The patients were divided into groups depending on the type of the diagnosis: 1)
      ALL, 2) ANLL, 3) HL, 4) NHL, 5) NBL, 6) Wilms tumor, 7) mesenchymal malignant
      tumor. The BMI SDS and the height SDS were evaluated. The difference in the
      incidence of disorders in each group was examined. RESULTS: In the study group at
      the time of the diagnosis 21.5% of patients were undernourished while 13.8%
      presented were overweight. Patients in the ALL group were overweight more often
      than the rest of the study group (RR 1.82, CI 95%1.26-2.63, p=0.002) - 18.6% of
      them were overweight. However, children with mesenchymal malignant tumor were
      less susceptible to overweight than the rest of the patients (RR 0.36, CI 95%0.15
      0.87, p=0.021) - only 5.4% of them were overweight. Girls with ALL were
      malnourished more often than other patients (RR 1.72, CI 95%1.08-2.75, p=0.03).
      There were no significant differences in the malnutrition/obesity frequency in
      other neoplasms groups. SUMMARY: ALL patients are less susceptible to underweight
      than the patients with the solid tumor. Moreover, the high incidence of
      overweight in children with ALL is noteworthy.

PMID- 29073291
TI  - [Direction of change in the somatic development in children and adolescents with
      type 1 diabetes].
AB  - INTRODUCTION: Disorders of somatic development in children and adolescents with
      type 1 diabetes can lead to unstable course of the disease and the difficulties
      in obtaining good metabolic control. AIM: Evaluation of somatic development in
      children and adolescents with type 1 diabetes in different age categories.
      MATERIAL AND METHODS: Agroup of 97 girls and 90 boys with type 1 diabetes was
      examined. Children were divided into three age groups: girls with mean age of
      9.1; 12.9; 16.2 years and boys with mean age of 7.6; 11.8; 16.2 years. In all
      subjects accurate anthropometric measurements and nutritional status assessment
      were conducted. Somatic traits and indices were expressed in terms of standard
      deviations of age and sex-specific Polish growth references. RESULTS: Body
      measurements in girls at the age of 9.1 years and boys at the age of 7.6 years
      did not differ significantly from the healthy population. Girls aged 12.9 years
      had significantly increased widths shoulder (p=0,003)) and greater body
      circumferences: waist (p=0,001), arm (p=0,0008) and hips (p=0,001). The boys aged
      11.8 years have significantly larger greater trunk length (p=0,04) and upper
      limbs length (p=0,01). The oldest girls, at the age of 16.2 years excessive body
      weight (p=0,00001) also significantly increased circumferences of waist and hips
      (p=0,000001) were observed. Boys aged 16.2 years also showed significantly
      increased body circumferences (p=0,0001) which was particularly evident for boys
      with greater body height. Body mass index BMI in girls pointed to the overweight
      (1.50 SDS) while in boys it was normal (-0.05 SDS). The youngest girls, the
      duration of the disease was 2.9 +/- 0.6 years, in the older group 5.2 +/- 0.6
      years and the oldest 6.9 +/- 0.6 years. The boys, the duration of illness was 1.9
      +/- 0.6 years; 2.6 +/- 0.5 years; 4.8 +/- 0.7 years. The mean HbA 1c in girls was
      7.1; 7.7; and 8.4%, while boys 7.4; 7.4 and 7.6%. CONCLUSIONS: Changes in body
      build in patients with diabetes type 1 are associated with chronological age,
      duration of disease and metabolic control. It has been observed that the increase
      of weight and waist circumference concern girls. Patients with overweight and
      obesity represent a risk of early development of complications and require
      special care.

PMID- 29073292
TI  - TOFI phenotype - its effect on the occurrence of diabetes.
AB  - Recent studies have reported a significant increase in the incidence of type 2
      diabetes in the past 30 years. They also predict that this trend will continue.
      This is related to a change in lifestyle, which results in a parallel increase in
      the incidence of overweight and obesity. However, symptoms of the metabolic
      syndrome, so far closely related to abdominal obesity, are relatively common
      among people with normal body mass index (BMI) and waist circumference. The aim
      of the study is to present the TOFI phenotype (thin outside, fat inside) as an
      important factor in pathogenesis of type 2 diabetes. In the 1980s, the first
      study of the MONW (metabolic obese normal weight), a phenotype that is
      characterized by metabolic diseases in people with normal body weight. Since
      then, no uniform criteria have been established for MONW deployment, which has
      created difficulties in identifying affected individuals. Recent work has
      appeared describing the TOFI phenotype, which seems to lead to the appearance of
      MONW. People affected by this problem, in spite of undersized fatty tissue, have
      an increased amount of adipose tissue surrounding the internal organs, which
      increases the risk of insulin resistance and type 2 diabetes. In the diagnostics
      of the TOFI phenotype, magnetic resonance imaging is of paramount importance.
      Previous studies did not provide clear answers about the pathogenesis of TOFI nor
      which factors stimulate its development. Prophylaxis and treatment of the
      syndrome include increased physical activity, the promotion of correct eating
      habits, and a use of metformin.

PMID- 29073293
TI  - Prader-Willi Syndrome - nutritional management in children, adolescents and
      adults.
AB  - Prader-Willi Syndrome is a genetic condition caused by an abnormality of
      chromosome 15, mostly resulting from a deletion.The prevalence of syndrome in
      Europe has been reported between 1 in 8,000 to 1 in 45,000 births. Characteristic
      features of the syndrome include hypotonia, short stature, psychomotor
      development delay, hypogonadism and progressive, life-threatening obesity.
      Treatment of Prader-Willi Syndrome consists of intensive rehabilitation,
      psychologicalcare, speech therapy and also, if patient is fulfilling appropriate
      criteria, growth hormone treatment. An extremely important element of therapy is
      also properly planned and implemented nutritional management. Adequate diet
      prevents the malnutrition in the first stage of life and the development of
      excessive weight in subsequent years. The aim of this article is to provide
      practical and accurate guidance on nutritional management and diet therapy for
      physicians and nutritionists who work with children, adolescents and adults with
      Prader-Willi Syndrome.

PMID- 29073294
TI  - Previously unreported abnormalities in Wolfram Syndrome Type 2.
AB  - Wolfram syndrome (WFS) is a rare autosomal recessive disease with non-autoimmune
      childhood onset insulin dependent diabetes and optic atrophy. WFS type 2 (WFS2)
      differs from WFS type 1 (WFS1) with upper intestinal ulcers, bleeding tendency
      and the lack ofdiabetes insipidus. Li-fespan is short due to related
      comorbidities. Only a few familieshave been reported with this syndrome with the
      CISD2 mutation. Here we report two siblings with a clinical diagnosis of WFS2,
      previously misdiagnosed with type 1 diabetes mellitus and diabetic retinopathy
      related blindness. We report possible additional clinical and laboratory findings
      that have not been pre-viously reported, such as asymptomatic hypoparathyroidism,
      osteomalacia, growth hormone (GH) deficiency and hepatomegaly. Even though not a
      requirement for the diagnosis of WFS2 currently, our case series confirm
      hypogonadotropic hypogonadism to be also a feature of this syndrome, as reported
      before.

PMID- 29073295
TI  - [Early enzyme replacement therapy - hope for patients with mucopolysaccharidosis
      Type II].
AB  - We present an unexpected outcome of 10 years of enzyme replacement therapy of a
      boy with mucopolysaccharidosis type II. Due to a positive familiar history
      (severe disease course in a sibling) the diagnosis was established in the first
      month of life. Treatment with Elaprase was introduced two months later. Since
      then normal physical and mental development is observed. The patient presents
      only relatively large head circumference (+2.1 SD) and slight decrease of joints
      mobility. In our opinion, early introduction of enzyme replecement therapy could
      attenuate the disease course.

PMID- 29073296
TI  - Assessment of selected lipid parameters in in children exposed to gestational
      diabetes (GDM) in utero.
AB  - INTRODUCTION: The assessment of maternal hyperglycemia during pregnancy and lipid
      profile in the offspring is recently highlighted. AIM: The study was undertaken
      to assess the selected lipid parameters in children exposed to gestational
      diabetes (GDM) in utero. MATERIAL AND METHODS: 50 children, 7-15 years of age,
      exposed to GDM were compared with 46 control subjects (7-16 years old). In all
      participants anthropometric parameters (height, weight, waist and hip
      circumferences) and values of total cholesterol, LDL-, HDL-cholesterol and
      triglycerides (TG) were measured. BMI, waist-to-hip ratio (WHR) and TG to HDL
      cholesterol ratio were calculated. RESULTS: The prevalence of overweight/obesity
      in the study cohort was 38% and 41% in the control (p=0.19). Higher total
      cholesterol level (p=0.002) and LDL-cholesterol (p=0.007) were found in the study
      group. In children exposed to GDM significantly higher values of LDL-cholesterol
      (p=0.02), triglycerides (p=0.02), TG to HDL-cholesterol ratio (p=0.007) and lower
      HDL-cholesterol (p=0.02) were observed in overweight/obese children compared to
      slim participants. In the control group, similar results were not noted. In the
      study group, a positive correlations of TG to HDL-cholesterol ratio and BMI SDS
      (RS=0.47, p=0.0006), WHR (RS =0.31, p=0.03), SDS of birth weight (RS =0.47,
      p=0.0006) were found. CONCLUSION: Children exposed to GDM in utero could have a
      higher risk of dyslipidemia with its cardiovascular complications. Towards
      observed worse lipid parameters in children with excessive body mass born from
      pregnancies with GDM, prevention of overweight and obesity in this group seems to
      be essential.

PMID- 29073297
TI  - Body posture in children with obesity - the relationship to physical activity
      (PA).
AB  - INTRODUCTION: The modern world of electronic devices offers children and young
      people various forms of leisure activities, while reducing the need for natural
      movement, necessary for normal psychomotor development. Sedentary life
      contributes to an increased body weight and, thereby, to the development of body
      posture abnormalities. The aim of the study was to evaluate body posture, leisure
      activities, and the number of hours spent using electronic devices among children
      with obesity. MATERIAL AND METHODS: The study involved 51 children with obesity
      (BMI above 95 percentile) - A group, and 69 children with normal body weight at
      the age of 9-13 years (10.98 +/- 1.29) - B group (control). Body posture has been
      evaluated with the scoliometer, the digital inclinometer and the plumb line. The
      hump ratio has been calculated on the basis of SOSORT recommendations. Time spent
      in front of electronic devices based on a questionnaire results has also been
      calculated. RESULTS: Children with obesity have more body posture defects in the
      sagittal plane than children with normal z-scores (p<0.001). 46.8% of children in
      group A have distorted depth of the two curvatures of the spine. In the control
      group, the majority of deviations have been observed in the evaluation of the ATR
      (Angle Trunk Rotation) at the lumbar spine (p<0.05), while in group A, at the
      level of the thoracic spine (40.42% vs. 23.07%). Both groups of respondents use
      electronic devices at least 3 days a week (p>0.05). Obese children often use
      mobile devices, while children with normal body weight often use desktop
      equipment. CONCLUSIONS: Definitely more body posture abnormalities are found in
      the group of obese children. Children use electronic devices regardless of
      weight. It is worth to expand educational activities with programs that improve
      the quality of body posture through a daily change of abnormal patterns.

PMID- 29073298
TI  - Polycystic ovary syndrome and diabetes mellitus type 1 in adult and adolescent
      females.
AB  - INTRODUCTION: The growing prevalence of type 1 diabetes mellitus (T1DM) and
      polycystic ovary syndrome (PCOS; the most frequent cause of anovulatory
      infertility) results in their growing comorbidity. OBJECTIVE: To review the
      available data on comorbidity of type 1 diabetes mellitus and the polycystic
      ovary syndrome and their relations, especially in the adolescent group. MATERIALS
      AND METHODS: The available medical databases have been searched to identify
      relevant bibliography; then analysis and synthesis of the available data have
      been conducted. RESULTS: At present, the prevalence of comorbid T1DM and PCOS in
      girls has not been established. CONCLUSION: The available data on T1DM and PCOS
      comorbidity in adult women suggest the need for early diagnostic investigations
      to detect their comorbidity and for early therapeutic interventions. Further
      research to investigate their coprevalence is necessary. In female adolescents,
      either with or without T1DM, PCOS should be diagnosed not earlier that two years
      after menarche or when at age of 16 menarche is still absent, with all of the
      three Rotterdam criteria met. In time between menarche and the end of second year
      of menstruation high/medium risk of PCOS can be identified. After the fourth year
      of menstruating, the patient should be treated as an adult. Such approach will
      eliminate differences in diagnosis resulting from different law definition of
      adulthood in various countries. In girls with T1DM treatment should be started
      for any individual component of PCOS to reduce the risk of progression of the
      syndrome.

PMID- 29073299
TI  - Musculoskeletal/Radiological Manifestations of Mucolipidosis II (I-Cell disease)
      in late Adolescence/Early Adulthood.
AB  - Mucolipidosis type II (I-Cell disease) is a rare autosomal recessive lysosomal
      disorder, resulting from functional deficiency of lysosomal enzymes due to an
      impaired targeting of the enzymes to lysosomes, which leads to an abnormal cell
      architecture and the overflow of lysosomal enzymes into the body fluids. The life
      expectancy of the patients is poor, with multisystem deterioration leading to
      death in early childhood. According to the available reports, patients with I
      cell disease do not survive beyond the first decade of life. Here, we describe
      and illustrate various radiological-musculoskeletal manifestations of a rare case
      of mucolipidosis II who has been a survivor up to now, 20 years old. The course
      of her disease has been complicated by early severe visual compromise due to
      optic nerve swelling, hearing loss and mitral valve regurgitation/stenosis,
      bilateral carpal tunnel, and severe growth impairment. Our case demonstrates
      several skeletal features of dysostosis multiplex. At the age of 20, she is
      wheelchair bound and her medical course is complicated by recurrent pneumonia,
      treated with multiple hospitalizations, antibiotics, and BiPAP. She is on
      outpatient palliative care, Do Not Resuscitate/Do Not Intubate (DNR/DNI) status.

PMID- 29073300
TI  - Continuous subcutaneous insulin infusion during total parenteral nutrition after
      gastroscopy complicated by duodenal intramural haematoma in a patient with type 1
      diabetes - case repor.
AB  - We present the course of the insulin therapy during total parenteral nutrition
      (TPN) after gastroscopy complicated by duodenal intramural haematoma, in a boy
      with type 1 diabetes treated with the insulin pump. There is a lack of guidelines
      regarding the insulin therapy during TPN in children. Additionally, duodenal
      intramural haematoma is a very rare complication of diagnostic gastroscopy. There
      are only few cases reported so far.

PMID- 29073301
TI  - [The coexistence of two independent disease units - Graves' disease and growth
      hormone deficiency in a 13 year old female patient].
AB  - INTRODUCTION: Graves' disease (MGB) is the most common cause of hyperthyroidism
      in children and adolescents. This condition is more common in girls than boys, in
      a ratio of about 5:1. The coexistence of Graves' disease (MGB) with growth
      hormone deficiency (GHD) is not common. Much more often GHD connects with
      hypothyroidism. CASE REPORT: We present the case of 13-year old female patient
      with Graves' disease, diagnosed at 10 years of age and growth hormone deficiency,
      which was confirmed at the age of 12. Currently, the girl was qualified to growth
      hormone therapy. CONCLUSIONS: 1) Described by our case is interesting because of
      the rarity of coexistence Graves' disease with growth hormone deficiency. 2) GH
      deficiency often accompanies hypothyroidism. Note, however, that hyperthyroidism
      may be associated with short stature in the course of growth hormone deficiency.
      3) The coexistence of endocrine disorders in childhood is not uncommon, so the
      diagnosis of one disease entity should not exclude further observation for the
      presence of other endocrine disorders.

PMID- 29073302
TI  - Potential Clinical Benefits of a Two-bag System for Fluid Management in Pediatric
      Intensive Care Unit Patients with Diabetic Ketoacidosis.
AB  - INTRODUCTION: Diabetic ketoacidosis (DKA) is a life-threatening complication of
      diabetes mellitus (DM) that requires appropriate treatment with insulin and
      intravenous fluids. Both one-bag and two-bag systems of fluid management are used
      to treat pediatric diabetic ketoacidosis. AIM OF THE STUDY: We compare the one
      bag and two-bag systems of fluid managementwith regard to incidence of
      hypoglycemia, serum bicarbonate correction, pH correction and discharge from the
      pediatric intensive care unit (PICU). METHOD: This was a retrospective study of
      61 patients less than 21 years old admitted to the PICU with a diagnosis of DKA.
      Of the 61 patients, 38 were treated with the one-bag system and 23 treated with
      the two-bag system. RESULTS: The two-bag system had significantly (p=0.03) lower
      incidence of hypoglycemia (n=2, 8.7%) compared to the one-bag system (n=13,
      34.2%). The two-bag system had significantly (p=0.001) fewer hours of PICU stay
      (M=29.6, SD=15.23) than the one-bag system (M=47.9, SD=22.32). However, there
      were no significant differences between the bag systems for hours for pH and
      bicarbonate correction. CONCLUSION: The two-bag system is associated with lower
      incidence of hypoglycemia and faster discharge from the PICU. We recommend that
      clinicians consider using the two-bag system for fluid management in pediatric
      patients with diabetic ketoacidosis.

PMID- 29073303
TI  - Significant differences in parameters of glucose metabolism in children of
      hypertensive and normotensive parents.
AB  - INTRODUCTION: In the recent years, alterations in the carbohydrate metabolism,
      including insulin resistance, are considered as risk factors in the development
      of hypertension and its complications in young age. Hypertension is associated
      with significant cardiovascular morbidity and mortality. The onset of pathology
      responsible for the development of hypertension, as well as levels of biomarkers
      specific for early stages of atherosclerosis are poorly understood. AIM: To
      compare a group of children whose parents have a history of hypertension (study
      group) with a group of children with normotensive parents (reference group), with
      consideration of typical risk factors for atherosclerosis, parameters of lipid
      and carbohydrate metabolism, anthropometric data and new biomarkers of early
      cardiovascular disease (hsCRP, adiponectin, sICAM-1). MATERIAL AND METHODS: The
      study population consists of 84 children. Of these, 40 children (mean age 13.6+/
      2.7 years) had a parental history of hypertension, and 44 aged 13.1+/-3.7 yrs
      were children of normotensive parents. Anthropometric measurements were taken,
      and measurements of blood pressure, lipid profile, glucose and insulin levels
      were carried out. The insulin resistance index (HOMA IR) was calculated. Levels
      of hsCRP, soluble cell adhesion molecules (sICAM) and adiponectin were measured.
      RESULTS: There were no statistically significant differences in anthropometric
      parameters (body mass, SDS BMI, skin folds) between groups. Values of systolic
      blood pressure were statistically significantly higher in the study group (Me 108
      vs. 100 mmHg, p= 0.031), as were glycaemia (Me 80 vs. 67 mg/dl p<0.001) and
      insulinaemia levels (Me 8.89 vs. 5.34 uIU/ml, p=0.024). Higher, statistically
      significant values of HOMA IR were found in the study group (children of
      hypertensive parents) (Me 1.68 vs. 0.80 mmol/l * mU/l, p=0.007). Lower
      adiponectin levels (Me 13959.45 vs. 16822 ng/ml, p=0.020) were found in children
      with a family history of hypertension. No significant differences were found in
      the levels of sICAM, hsCRP, and parameters of lipid metabolism. CONCLUSIONS:
      Family history of hypertension is correlated with higher values of systolic blood
      pressure and higher values of parameters for carbohydrate metabolism in children.
      Hypertension in parents is a risk factor for cardiovascular disease in their
      children.

PMID- 29073304
TI  - Environmental factors affecting management of type 1 diabetes in children below
      the age of 10.
AB  - INTRODUCTION: The way parents manage diabetes of their small children and
      environmental influence are crucial for maintaining glycemic control. The aim of
      the study was to assess environmental factors affecting metabolic control of
      young children with T1D treated with insulin pumps. MATERIAL AND METHODS: Parents
      of children with T1D under the age of 10 years completed: General Self-Efficacy
      Scale, Parental Diabetes Quality of Life Questionnaire, Beck Depression Inventory
      and a questionnaire on socioeconomic factors. RESULTS: There were analyzed 165
      questionnaires. 66% of children achieved HbA1c <7.5% (<58mmol/mol). Factors
      associated with HbA1c>=7.5% (>=58mmol/mol) in the multiple logistic regression:
      single-parent families (p=0.003), low income <250EURO (p=0.017), parental
      education (p<0.05), snacking without parents' permission (p=0.0006) and in
      parents of children >=6 year of age - quality of life (p=0.037). In families of
      children <6 year of age, parents had higher self-efficacy than parents of
      children >=6 year of age (p=0.046). CONCLUSIONS: Parents of young children are
      not homogeneous group and face different challenges. Young children of parents
      withlower education level and living in single-parent families are at high risk
      of poor diabetes management. More attention should be paid to the problem of
      young children snacking without parents' permission. ABBREVIATIONS: BDI - Beck
      Depression Inventory, CI-Confidence Intervals, GSES - General Self-Efficacy
      Scale, HbA1c - glycated hemoglobin, OR- Odds Ratio, PDQOLQ - Parental Diabetes
      Quality of Life Questionnaire, T1D - type 1 diabetes.

PMID- 29073305
TI  - [Topinambour - nutritional and medical properties of the Jerusalem artichoke
      (Helianthus tuberoses L.)].
AB  - Topinambour (Helianthus tuberosus L.), also known as the Jerusalem artichoke is a
      plant, which origins from North America. In XVII century it was brought to the
      Europe. For ages it was cultivated due to edible tuber and its healing
      properties.The aim of the article is to present medical properties and
      application of topinmbour in patient's diet. Many studies were performed on
      animals to specify medical properties of topinambour. Results show, that
      topinambour lowers plasma glucose, total cholesterol and triglyceride levels. It
      is believed that these effects are caused by high level of inulin present it its
      tuber.Inulin effect on the human organism was assessed in many clinical studies.
      It is thought it has prebiotic features, lowers plasma glucose and intestinal pH
      level, which results in higher calcium bioavailability. Additionaly, it has a
      positive impact on the plasma lipid profile, acts as an immunomodulator,
      affecting digestive systems' limfatic tissue. Due to its characteristics, it can
      be used in the diet of obese and type 2 diabetes mellitus patients.Recently, it
      was discovered that topinambour tuber secretion works as a cytotoxic agent contra
      breast cancer cells.

PMID- 29073306
TI  - [Y chromosome in Turner syndrome].
AB  - Turner syndrome (TS) is an inherited genetic disorder caused by numerical and/or
      structural chromosome X aberrations occurring at a frequency of 1:1200-1:2500
      live-born girls. The most common karyotype is X chromosome monosomy (45,X)
      (approximately 50-60% of cases). Approximately 5-6% of patients may have abnormal
      Y chromosome or mosaicism characterized by the coexistence of 45,X cell line with
      cell line in which all or part of chromosome Y is present. In patients with TS
      who have all or fragmented genetic material from chromosome Y there is a
      substantial risk of cancerous lesions in these dysgenetic gonads. This paper
      stands for the review of the current knowledge on the genetic material of the Y
      chromosome in TS, especially in view of the risk of developing malignancies such
      as gonadoblastoma and dysgerminoma.

PMID- 29073307
TI  - A follow-up history of young man with apparent cortisone reductase deficiency
      (ACRD) - several years after diagnosis.
AB  - INTRODUCTION: Inactivating mutations in the enzyme hexose-6-phosphate
      dehydrogenase (H6PDH), the enzyme responsible for NADPH generation playing
      critical role in 11-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activity,
      cause apparent cortisone reductase deficiency (ACRD). It leads to increased
      metabolic clearance rate of cortisol due to a defect in cortisone to cortisol
      conversion by 11b-HSD1. We want to analyse the process of the disease, efficacy
      of long-lasting treatment with glucocorticoids throughout childhood and
      adolescence in only male patient with ACRD. CASE PRESENTATION: A 23 year-old male
      patient was diagnosed with ACRD at the age of 7 years. The clinical manifestation
      of ACRD was presented by precocious pubarche. His bone age was assessed as 11.5
      years old. Blood tests indicated increased the plasma androgen, with elevated 17
      hydroxyprogesterone concentration. A steroid profile analysis of a 24-h urine
      collection showed extremely reduced THF + allo-THF/THE ratio - 0.021 (normal
      range: 0.7-1.2). Two months of hydrocortisone therapy was ineffective and
      dexamethasone was administered in initial dose of 0.375 mg/24 h. Next dosage
      beetwen 0.125 mg/24h and 0.375 mg/24h has been changed depending on the patient's
      results of laboratory tests and condition. Control laboratory studies indicated
      suppression of excess adrenal androgen synthesis, but we never got the THF + allo
      THF/THE ratio in normal values. He did not develop any serious side effects,
      although dexamethasone is the most potent adrenal suppression drug. CONCLUSIONS:
      Hydrocortisone treatment is ineffective in ACRD patients because it was rapidly
      metabolized to cortisone. We have found the balance between the dexamethasone
      treatment effects of adrenal suppression and the achievement of full height
      potential considering the condition of our patient.

PMID- 29073308
TI  - 15-Year old girl with APS type IIIc, 12 months post-thymectomy remission of
      myasthenia.
AB  - Polyglandular autoimmune syndromes (PAS) is a group of heterogenous conditions
      characterized by the association of at least two organ-specific autoimmune
      disorders, concerning both endocrine and non-endocrine organs. Type III is
      defined as the combination of autoimmune thyroid disease and other autoimmune
      condition (other than Addison's disease) and is divided into four subtypes. We
      describe a teenage female patient - with the family history of autoimmune
      diseases, who has simultaneously developed the symptoms of autoimmune thyroid
      disease with the clinical picture of hyperthyroidism and myasthenia gravis at the
      age of fifteen. Graves' disease was diagnosed approximately 2 months before
      myasthenia. Co-occurance of those two diseases allowed us to diagnose PAS type
      IIIC, however it caused specific diagnostic and treatment difficulties.
      Furthermore, several months after the diagnosis the patient was found to be GAD
      Ab positive, whilst the glycaemic control remained normal. No evidence of other
      autoimmune conditions was observed. This patient received the standard GD and MG
      treatment. When the CT scan revealed thymus enlargement, thymectomy was
      performed. After the surgery we have observed not only remission of MG, but also
      a significant decrease of TRAb as well, that lasted for a year after the
      thymectomy. Our patient's case suggests that in patients diagnosed with PAS, the
      organ-specific Ab screening can help identify other latent and subclinical
      autoimmune diseases before clinical symptoms develop. The achievement of post
      thymectomy remission of both MG and GD may indicate a close immunological
      relationship between PAS components.

PMID- 29073309
TI  - Thinking Outside the Checkbox.
AB  - A 34-year-old, previously healthy Japanese man developed a dry cough. He did not
      have dyspnea, nasal discharge, sore throat, facial pain, nasal congestion, or
      postnasal drip. His symptoms persisted despite several courses of antibiotics
      (from different physicians), including clarithromycin, minocycline, and levofl
      oxacin. A chest x-ray after 2 months of symptoms and a noncontrast chest computed
      tomography (CT) after 4 months of symptoms were normal, and bacterial and
      mycobacterial sputum cultures were sterile. Treatment with salmeterol and fl
      uticasone was ineffective.

PMID- 29073310
TI  - Opportunities and Challenges for Improving the Patient Experience in the Acute
      and Postacute Care Setting Using Patient Portals: The Patient's Perspective.
AB  - Efforts to improve the patient experience are increasingly focusing on engaging
      patients and their "care partners" by using patient portals. The Acute Care
      Patient Portal Task Force was supported by the Gordon and Betty Moore Foundation
      to convene a national meeting of an interdisciplinary group of stakeholders,
      including patient advocates, to consider how the acute and postacute care patient
      experience can be improved by using patient-facing technologies. We identified
      key opportunities and challenges for enhancing cognitive support, promoting
      respect while maintaining boundaries, and facilitating patient and family
      empowerment through the lens of the patient. Institutions, clinicians, and
      vendors would benefit tremendously by considering these 3 patient-centered themes
      when partnering with patients and family advisors to implement and realize the
      full potential of patient portals to enhance the acute and postacute care
      experience.

PMID- 29073311
TI  - Expanding Treatment Opportunities for Hospitalized Patients with Opioid Use
      Disorders.
AB  - The prevalence of opioid use disorders (OUDs) is rising across the United States.
      Patients with OUDs are often hospitalized for medical conditions other than
      addiction, such as infection, injury, or pregnancy. These hospital admissions
      provide an opportunity for healthcare providers to initiate opioid agonist
      therapy with methadone or buprenorphine. Randomized trials have demonstrated the
      superior effectiveness of this treatment strategy, but its adoption by hospital
      providers has been slow. A number of barriers have impeded its implementation,
      including misperceptions about the regulation of opioid prescribing, limited
      resources for the transition to community- based treatment, and a lack of
      familiarity among clinicians about the appropriate initiation and dose adjustment
      of these opioid agonists for maintenance therapy. We discuss changes in policy
      and practice to expand opportunities to engage patients with OUDs in opioid
      agonist treatment during their inpatient hospitalizations.

PMID- 29073312
TI  - Vascular Ultrasonography: A Novel Method to Reduce Paracentesis Related Major
      Bleeding.
AB  - Paracentesis is a core competency for hospitalists. Using ultrasound for fluid
      localization is standard practice and involves a low-frequency probe. Experts
      recommend a "2-probe technique, " which incorporates a high-frequency ultrasound
      probe in addition to the low-frequency probe to identify blood vessels within the
      intended needle path. Evidence is currently lacking to support this 2-probe
      technique, so we performed a pre- to postintervention study to evaluate its
      effect on paracentesis-related bleeding complications. From February 2010 to
      August 2011, procedures were performed using only low-frequency probes
      (preintervention group), while the 2-probe technique was used from September 2011
      to February 2016 (postintervention group). A total of 5777 procedures were
      performed. Paracentesis-related minor bleeding was similar between groups. Major
      bleeding was lower in the postintervention group (3 [0.3%], n = 1000 vs 4
      [0.08%], n = 4777; P = 0.07). This clinically meaningful trend suggests that
      using the 2-probe technique might prevent paracentesis-related major bleeding.

PMID- 29073313
TI  - Things We Do For No Reason: Echocardiogram in Unselected Patients with Syncope.
AB  - Syncope is a common cause of emergency department visits and hospitalizations.
      Echocardiogram is frequently used as a diagnostic tool in the evaluation of
      syncope, performed in 39% to 91% of patients. The diagnostic yield of
      echocardiogram for detecting clinically important abnormalities in patients with
      a normal history, physical examination, and electrocardiogram (ECG), however, is
      extremely low. In contrast, echocardiograms performed on patients with syncope
      with a positive cardiac history, abnormal examination, and/or ECG identify an
      abnormality in up to 29% of cases, though these abnormalities are not always defi
      nitively the cause of symptoms. Recently updated clinical guidelines for syncope
      management from the American College of Cardiology now recommend echocardiogram
      only if initial history or examination suggests a cardiac etiology, or ECG is
      abnormal. Universal echocardiography in patients with syncope exposes a signifi
      cant number of patients to unnecessary testing and cost and does not represent
      evidence-based or high-value patient care.

PMID- 29073315
TI  - Derivation of a Clinical Model to Predict Unchanged Inpatient Echocardiograms.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) is one of the most commonly
      ordered tests in healthcare. Repeat TTE, defined as a TTE done within 1 year of a
      prior TTE, represents 24% to 42% of all studies. The purpose of this study was to
      derive a clinical prediction model to predict unchanged repeat TTE, with the goal
      of defining a subset of studies that are unnecessary. METHODS: Single-center
      retrospective cohort study of all hospitalized patients who had a repeat TTE
      between October 1, 2013, and September 30, 2014. RESULTS: Two hundred eleven of
      601 TTEs were repeat studies, of which 78 (37%) had major changes. Five variables
      were independent predictors of major new TTE changes, including history of
      intervening acute myocardial infarction, cardiothoracic surgery, major new
      electrocardiogram (ECG) changes, prior valve disease, and chronic kidney disease.
      Using the beta-coefficient for each of these variables, we defined a clinical
      prediction model that we named the CAVES score. The acronym CAVES stands for
      chronic kidney disease, acute myocardial infarction, valvular disease, ECG
      changes, and surgery (cardiac). The prevalence of major TTE change for the full
      cohort was 35%. For the group with a CAVES score of -1, that probability was only
      5.6%; for the group with a score of 0, the probability was 17.7%; and for the
      group with a score >=1, the probability was 55.3%. The bootstrap corrected C
      statistic for the model was 0.78 (95% confidence interval, 0.72-0.85), indicating
      good discrimination. CONCLUSIONS: Overall, the CAVES score had good
      discrimination and calibration. If further validated, it may be useful to predict
      repeat TTEs that are unlikely to have major changes.

PMID- 29073316
TI  - Observational Study of Peripheral Intravenous Catheter Outcomes in Adult
      Hospitalized Patients: A Multivariable Analysis of Peripheral Intravenous
      Catheter Failure.
AB  - BACKGROUND: Almost 70% of hospitalized patients require a peripheral intravenous
      catheter (PIV), yet up to 69% of PIVs fail prior to completion of therapy.
      OBJECTIVE: To identify risk factors associated with PIV failure. DESIGN: A single
      center, prospective, cohort study. SETTING: Medical and surgical wards of a
      tertiary hospital located in Queensland, Australia. PARTICIPANTS: Adult patients
      requiring a PIV. MEASUREMENTS: Demographic, clinical, and potential PIV risk
      factors were collected. Failure occurred if the catheter had complications at
      removal. RESULTS: We recruited 1000 patients. Catheter failure occurred in 512
      (32%) of 1578 PIVs. Occlusion/infiltration risk factors included intravenous (IV)
      flucloxacillin (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.19
      3.31), 22-gauge PIVs (HR, 1.43; 95% CI, 1.02-2.00), and female patients (HR,
      1.48; 95% CI, 1.10-2.00). Phlebitis was associated with female patients (HR,
      1.81; 95% CI, 1.40-2.35), bruised insertion sites (HR, 2.16; 95% CI, 1.26-3.71),
      IV flucloxacillin (HR, 2.01; 95% CI, 1.26-3.21), and dominant side insertion (HR,
      1.39; 95% CI, 1.09-1.77). Dislodgement risks were a paramedic insertion (HR,
      1.78; 95% CI, 1.03-3.06).Each increase by 1 in the average number of daily PIV
      accesses was associated (HR 1.11, 95% CI 1.03-1.20)-(HR 1.14, 95% CI 1.08-1.21)
      with occlusion/infiltration, phlebitis and dislodgement. Additional securement
      products were associated with less (HR 0.32, 95% C-0.46)-(HR 0.63, 95% CI 0.48
      0.82) occlusion/infiltration, phlebitis and dislodgement. CONCLUSION: Modifiable
      risk factors should inform education and inserter skill development to reduce the
      currently high rate of PIV failure.

PMID- 29073314
TI  - The SDM 3 Circle Model: A Literature Synthesis and Adaptation for Shared Decision
      Making in the Hospital.
AB  - Patient engagement through shared decision-making (SDM) is increasingly seen as a
      key component for patient safety, patient satisfaction, and quality of care.
      Current SDM models do not adequately account for medical and environmental
      contexts, which may influence medical decisions in the hospital. We identified
      leading SDM models and reviews to inductively construct a novel SDM model
      appropriate for the inpatient setting. A team of medicine and pediatric
      hospitalists reviewed the literature to integrate core SDM concepts and processes
      and iteratively constructed a synthesized draft model. We then solicited broad
      SDM expert feedback on the draft model for validation and further refinement. The
      SDM 3 Circle Model identifies 3 core categories of variables that dynamically
      interact within an "environmental frame." The resulting Venn diagram includes
      overlapping circles for (1) patient/family, (2) provider/team, and (3) medical
      context. The environmental frame includes all external, contextual factors that
      may influence any of the 3 circles. Existing multistep SDM process models were
      then rearticulated and contextualized to illustrate how a shared decision might
      be made. The SDM 3 Circle Model accounts for important environmental and
      contextual characteristics that vary across settings. The visual emphasis
      generated by each "circle" and by the environmental frame direct attention to
      often overlooked interactive forces and has the potential to more precisely
      define, promote, and improve SDM. This model provides a framework to develop
      interventions to improve quality and patient safety through SDM and patient
      engagement for hospitalists.

PMID- 29073317
TI  - The Diagnostic Yield of Noninvasive Microbiologic Sputum Sampling in a Cohort of
      Patients with Clinically Diagnosed Hospital-Acquired Pneumonia.
AB  - The clinical predictors of positive sputum culture have not been previously
      reported in hospital-acquired pneumonia (HAP), and data on yield of sputum
      culture in this setting are scant. Current Infectious Disease Society of America
      guidelines for HAP recommend noninvasive sputum sampling, though the data for
      this practice are limited. We assessed the yield of sputum culture in HAP cases
      at an academic medical center from January 2007 to July 2013. HAP cases were
      identifi ed by International Classifi cation of Diseases, Ninth Revision-Clinical
      Modifi cation codes for bacterial pneumonia and all cases were validated by chart
      review. Our cohort had 1172 hospitalizations with a HAP diagnosis. At least 1
      sputum specimen was collected noninvasively and sent for bacterial culture after
      hospital day 2 and within 7 days of HAP diagnosis in 344 of these
      hospitalizations (29.4%), with a total of 478 sputum specimens, yielding 63
      (13.2%) positive, 109 (22.8%) negative, and 306 (64.0%) contaminated cultures
      (>10 epithelial cells per high power fi eld). Signifi cant predictors of a
      positive sputum culture were chronic lung disease (relative risk [RR] = 2.0; 95%
      confi dence interval [CI], 1.2-3.4) and steroid use (RR = 1.8; 95% CI, 1.1-3.2).
      The most commonly identifi ed organisms were Gram-negative rods not further
      speciated (25.9%), Staphylococcus aureus (21.0%), and Pseudomonas aeruginosa
      (14.8%). Because of the ease of obtaining a sputum sample combined with the
      prevalence of commonly drug-resistant organisms, we suggest that sputum culture
      in HAP is a potentially useful noninvasive diagnostic technique.

PMID- 29073318
TI  - Bedside Assessment of the Necessity of Daily Lab Testing for Patients Nearing
      Discharge.
AB  - As part of the Choosing Wisely(r) campaign, the Society of Hospital Medicine
      recommends against performing "repetitive complete blood count chemistry testing
      in the face of clinical and lab stability." With this recommendation as a
      framework, we targeted 2 hospitalist-run inpatient medicine units that employed
      bedside, scripted, interdisciplinary rounds. Our multifaceted intervention
      included prompting the hospitalist to identify clinically stable patients for
      next-day discharge and to discontinue labs when appropriate. It was coupled with
      the education of the clinicians and a regular data review for the hospitalists
      and unit staff. Among 2877 discharges included in a 1-year period, there was a
      significantly decreasing trend after the intervention in the percentage of
      patients getting labs in the 24, 48, and 72 hours before discharge (-1.87%, 
      1.47%, and -0.74% decrease per month, respectively; P < 0.05). Our structured,
      multifaceted approach effectively reduced daily lab testing in the 24 to 48 hours
      prior to discharge.

PMID- 29073322
TI  - Mindfulness in the Context of Romantic Relationships: Initial Development and
      Validation of the Relationship Mindfulness Measure.
AB  - Trait mindfulness and mindfulness in the context of romantic relationships may
      not be completely overlapping constructs. This study adapted an existing measure
      of trait mindfulness to assess the tendency to be mindful in romantic
      relationships, the Relationship Mindfulness Measure (RMM). Using data from 185
      young adults, the results supported the RMM's internal consistency, test-retest
      reliability, and concurrent and predictive validity. The RMM accounted for a
      significant portion of variance in positive relationship quality, negative
      relationship quality, and anxious and avoidant attachment, even after controlling
      for trait mindfulness. Based on these findings, assessing relationship
      mindfulness may improve research exploring the role of mindfulness in romantic
      relations and therefore facilitate the development and refinement of mindfulness
      training programs for couples.

PMID- 29073324
TI  - Is It Rational to Pursue Zero Suicides Among Patients in Health Care?
AB  - Suicide prevention is a major health care responsibility in need of new
      perspectives. This study reviews Zero Suicide, an emerging approach to suicide
      prevention that embraces the aspirational goal of zero suicides among patients
      treated in health care systems or organizations. Zero Suicide is gaining
      international momentum while at the same time evoking objections and concerns.
      Fundamental to Zero Suicide is a multilevel system view on suicide prevention,
      with three core elements: a direct approach to suicidal behaviors; continual
      improvement of the quality and safety of care processes; and an organizational
      commitment to the aspirational goal of zero suicides. The rationale and evidence
      for these components are clarified and discussed against the backdrop of concerns
      and objections that focus on possible undesired consequences of the pursuit of
      zero suicide, in particular for clinicians and for those who are bereaved by
      suicide. It is concluded that it is rational to pursue zero suicides as an
      aspirational goal, provided the journey toward zero suicides is undertaken in a
      systemic and sustained manner, in a way that professionals feel supported,
      empowered, and protected against blame and inappropriate guilt.

PMID- 29073323
TI  - Urinalysis of MMX-mesalazine as a tool to monitor 5-ASA adherence in daily IBD
      practice.
AB  - Adherence is pivotal but challenging in ulcerative colitis (UC) treatment. Many
      methods to assess adherence are subjective or have limitations. (Nac-)5
      aminosalicylic acid (5-ASA) urinalysis by high-performance liquid chromatography
      (HPLC) seems feasible and reproducible in healthy volunteers. We performed a
      prospective study in adult quiescent UC patients to evaluate the feasibility of
      spot (Nac-)5-ASA urinalysis by HPLC to assess adherence in daily inflammatory
      bowel disease (IBD) care. Twenty-nine patients (51.7% male, mean age 52 +/- 11
      years) were included (median FU 9 months) and weekly spot urine samples were
      collected. We found large variation in spot (Nac-)5-ASA urinary excretion that
      was unrelated to brand, dosing schedule or dosage of 5-ASA. In conclusion, spot
      (Nac-)5-ASA urinalysis is not applicable to assess 5-ASA adherence in daily IBD
      care.

PMID- 29073325
TI  - Risk prediction for heterogeneous populations with application to hospital
      admission prediction.
AB  - This article is motivated by the increasing need to model risk for large hospital
      and health care systems that provide services to diverse and complex patients.
      Often, heterogeneity across a population is determined by a set of factors such
      as chronic conditions. When these stratifying factors result in overlapping
      subpopulations, it is likely that the covariate effects for the overlapping
      groups have some similarity. We exploit this similarity by imposing structural
      constraints on the importance of variables in predicting outcomes such as
      hospital admission. Our basic assumption is that if a variable is important for a
      subpopulation with one of the chronic conditions, then it should be important for
      the subpopulation with both conditions. However, a variable can be important for
      the subpopulation with two particular chronic conditions but not for the
      subpopulations of people with just one of those two conditions. This assumption
      and its generalization to more conditions are reasonable and aid greatly in
      borrowing strength across the subpopulations. We prove an oracle property for our
      estimation method and show that even when the structural assumptions are
      misspecified, our method will still include all of the truly nonzero variables in
      large samples. We demonstrate impressive performance of our method in extensive
      numerical studies and on an application in hospital admission prediction and
      validation for the Medicare population of a large health care provider.

PMID- 29073326
TI  - Humility, Forgiveness, and Emerging Adult Female Romantic Relationships.
AB  - Among a sample of emerging adult females (N = 152) we empirically examined the
      role of humility and forgiveness in romantic relationships. We specifically
      tested a model linking perceived humility to relationship satisfaction with self
      forgiveness and partner-forgiveness. Participants in a romantic relationship
      completed measures of self-reported humility, self-forgiveness, partner
      forgiveness, and relationship satisfaction. Serial mediation analyses were
      conducted using path analysis to test the following sequence, humility self
      forgiveness partner-forgiveness relationship satisfaction. Findings indicate that
      humility was related to relationship satisfaction via a serially mediated path of
      self-forgiveness and partner-forgiveness, which was not reducible to impression
      management. We consider implications for research and clinical practice.

PMID- 29073328
TI  - Internal Targeting and External Control: Phototriggered Targeting in
      Nanomedicine.
AB  - The photochemical control of structure and reactivity bears great potential for
      chemistry, biology, and life sciences. A key feature of photochemistry is the
      spatiotemporal control over secondary events. Well-established applications of
      photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology
      (PP). However, although both are highly localizable through the application of
      light, they lack cell- and tissue-specificity. The combination of nanomaterial
      based drug delivery and targeting has the potential to overcome limitations for
      many established therapy concepts. Even more privileged seems the merger of
      nanomedicine and cell-specific targeting (internal targeting) controlled by light
      (external control), as it can potentially be applied to many different areas of
      medicine and pharmaceutical research, including the aforementioned PDT and PP. In
      this review a survey of the interface of photochemistry, medicine and targeted
      drug delivery is given, especially focusing on phototriggered targeting in
      nanomedicine.

PMID- 29073327
TI  - Estimation of cis-eQTL effect sizes using a log of linear model.
AB  - The study of expression Quantitative Trait Loci (eQTL) is an important problem in
      genomics and biomedicine. While detection (testing) of eQTL associations has been
      widely studied, less work has been devoted to the estimation of eQTL effect size.
      To reduce false positives, detection methods frequently rely on linear modeling
      of rank-based normalized or log-transformed gene expression data. Unfortunately,
      these approaches do not correspond to the simplest model of eQTL action, and thus
      yield estimates of eQTL association that can be uninterpretable and inaccurate.
      In this article, we propose a new, log-of-linear model for eQTL action, termed
      ACME, that captures allelic contributions to cis-acting eQTLs in an additive
      fashion, yielding effect size estimates that correspond to a biologically
      coherent model of cis-eQTLs. We describe a non-linear least-squares algorithm to
      fit the model by maximum likelihood, and obtain corresponding p-values. We
      perform careful investigation of the model using a combination of simulated data
      and data from the Genotype Tissue Expression (GTEx) project. Our results reveal
      little evidence for dominance effects, a parsimonious result that accords with a
      simple biological model for allele-specific expression and supports use of the
      ACME model. We show that Type-I error is well-controlled under our approach in a
      realistic setting, so that rank-based normalizations are unnecessary.
      Furthermore, we show that such normalizations can be detrimental to power and
      estimation accuracy under the proposed model. We then show, through effect size
      analyses of whole-genome cis-eQTLs in the GTEx data, that using standard
      normalizations instead of ACME noticeably affects the ranking and sign of
      estimates.

PMID- 29073330
TI  - Cox regression model with doubly truncated data.
AB  - Truncation is a well-known phenomenon that may be present in observational
      studies of time-to-event data. While many methods exist to adjust for either left
      or right truncation, there are very few methods that adjust for simultaneous left
      and right truncation, also known as double truncation. We propose a Cox
      regression model to adjust for this double truncation using a weighted estimating
      equation approach, where the weights are estimated from the data both
      parametrically and nonparametrically, and are inversely proportional to the
      probability that a subject is observed. The resulting weighted estimators of the
      hazard ratio are consistent. The parametric weighted estimator is asymptotically
      normal and a consistent estimator of the asymptotic variance is provided. For the
      nonparametric weighted estimator, we apply the bootstrap technique to estimate
      the variance and confidence intervals. We demonstrate through extensive
      simulations that the proposed estimators greatly reduce the bias compared to the
      unweighted Cox regression estimator which ignores truncation. We illustrate our
      approach in an analysis of autopsy-confirmed Alzheimer's disease patients to
      assess the effect of education on survival.

PMID- 29073331
TI  - Family Rituals in Low-Income African American Families at Risk for Trauma
      Exposure and Associations with Toddlers' Regulation of Distress.
AB  - This study included 75 mother-father-toddler triadic low-income families. Mothers
      and fathers reported separately on their own posttraumatic stress disorder (PTSD)
      symptoms and family rituals while children were rated by an independent observer
      during an emotionally eliciting task on key indicators of regulation of distress.
      Regression analyses supported a significant association between key dimensions of
      family rituals and Toddlers' regulation of distress: occurrence, continuation,
      and spirituality. Effect sizes of tested relationships were strong, ranging from
      25% to 36% of variance in children's distress explained. Family rituals are a
      salient intervention target in families and specifically help support children's
      developing emotion regulation competencies. Certain dimensions of family rituals
      may be particularly relevant to African American families, considering cultural
      resiliency factors. Clinical implications are discussed.

PMID- 29073329
TI  - Comparative risks of diabetes-related complications of basal insulins: a
      longitudinal population-based cohort of type 1 diabetes 1999-2013 in Taiwan.
AB  - AIM: We compared the effects of two types of basal insulin: long-acting insulin
      analogues vs. intermediate/long-acting human insulin, on diabetes-related
      complications in type 1 diabetes. METHODS: A total of 1188 patients with type 1
      diabetes who had recently started on long-acting insulin analogues or
      intermediate/long-acting human insulin were identified in 2004-2008 and followed
      until death or the end of 2013. Clinical outcomes included acute (i.e.
      hyperglycaemia, hypoglycaemia) and chronic (i.e. nephropathy, retinopathy,
      neuropathy, cardiovascular diseases) complications. Diabetes-related
      complications were measured as a composite outcome which included acute and
      chronic complications. Cox proportional hazards models were used to assess the
      time to event hazard ratio. Three propensity score (PS) methods were applied to
      adjust for baseline imbalances between basal insulin groups, including the PS
      matching approach (as the main analysis), standardized mortality ratio weighting
      (SMRW) and inverse probability of treatment weighting (IPTW). RESULTS: Long
      acting insulin analogues vs. intermediate/long-acting human insulin had a lower
      risk for a composite of diabetes-related complications {adjusted hazards ratios
      [aHRs] [95% confidence interval (CI)] 0.782 [0.639, 0.956], 0.743 [0.598, 0.924]
      and 0.699 [0.577, 0.846] according to the PS-matching approach, SMRW and IPTW,
      respectively}. Compared with intermediate/long-acting human insulin, using long
      acting insulin analogues had a lower hypoglycaemia risk: aHRs (95% CI) 0.681
      (0.498, 0.930), 0.662 (0.466, 0.943) and 0.639 (0.471, 0.867) from the PS
      matching approach, SMRW and IPTW, respectively. No statistical differences were
      found between two types of insulin on individual chronic complications.
      CONCLUSION: A trend of lower diabetes-related complications associated with long
      acting insulin analogues vs. intermediate/long-acting human insulin was observed.
      A reduced hypoglycaemia risk with long-acting insulin analogues was confirmed in
      this 'real-world' study.

PMID- 29073332
TI  - Numerical methods for polyline-to-point-cloud registration with applications to
      patient-specific stent reconstruction.
AB  - We present novel numerical methods for polyline-to-point-cloud registration and
      their application to patient-specific modeling of deployed coronary artery stents
      from image data. Patient-specific coronary stent reconstruction is an important
      challenge in computational hemodynamics and relevant to the design and
      improvement of the prostheses. It is an invaluable tool in large-scale clinical
      trials that computationally investigate the effect of new generations of stents
      on hemodynamics and eventually tissue remodeling. Given a point cloud of strut
      positions, which can be extracted from images, our stent reconstruction method
      aims at finding a geometrical transformation that aligns a model of the
      undeployed stent to the point cloud. Mathematically, we describe the undeployed
      stent as a polyline, which is a piecewise linear object defined by its vertices
      and edges. We formulate the nonlinear registration as an optimization problem
      whose objective function consists of a similarity measure, quantifying the
      distance between the polyline and the point cloud, and a regularization
      functional, penalizing undesired transformations. Using projections of points
      onto the polyline structure, we derive novel distance measures. Our formulation
      supports most commonly used transformation models including very flexible
      nonlinear deformations. We also propose 2 regularization approaches ensuring the
      smoothness of the estimated nonlinear transformation. We demonstrate the
      potential of our methods using an academic 2D example and a real-life 3D
      bioabsorbable stent reconstruction problem. Our results show that the
      registration problem can be solved to sufficient accuracy within seconds using
      only a few number of Gauss-Newton iterations.

PMID- 29073333
TI  - Low-dose glucocorticoids in rheumatoid arthritis: blurring the line between
      therapeutic dose and substitution therapy?
AB  - We would like to thank Masi and colleagues for their interest in our paper as
      well as for the interesting comments regarding the potential usefulness of
      neuroendocrine immune (NEI) testing in patients with rheumatoid arthritis (RA).
      When the first patient with rheumatoid arthritis (RA) was treated with
      glucocorticoids (GCs) in 1948, the effect was just overwhelming for that time.
      This article is protected by copyright. All rights reserved.

PMID- 29073334
TI  - Hypothesis: Can neuroendocrine immune (NEI) testing of individual RA patients
      guide benefits to harms ratio in glucocorticoid therapy?
AB  - We compliment and endorse the "Official View" by Palmowsky Y and the
      multidisciplinary experts on their review of guidelines for glucocorticoid (GC)
      therapy in rheumatoid arthritis (RA) (1). The guidelines generally agreed that
      GCs are an appropriate option for RA therapy, especially at low doses and for a
      short duration (1). However, the recommendations lacked evidence and guidance on
      doses, timing, and duration of GC use. Authors concluded that high-quality
      studies of GCs in RA are urgently needed (1). This article is protected by
      copyright. All rights reserved.

PMID- 29073335
TI  - In-Situ Microfluidic Study of Biphasic Nanocrystal Ligand-Exchange Reactions
      Using an Oscillatory Flow Reactor.
AB  - Oscillatory flow reactors provide a surface energy-driven approach for
      automatically screening reaction conditions and studying reaction mechanisms of
      biphasic nanocrystal ligand-exchange reactions. Sulfide and cysteine ligand
      exchange reactions with as-synthesized CdSe quantum dots (QDs) are chosen as two
      model reactions. Different reaction variables including the new-ligand-to-QD
      ratio, the size of the particles, and the original ligand type are examined
      systematically. Based on the in situ-obtained UV/Vis absorption spectra during
      the reaction, we propose two different exchange pathways for the sulfide exchange
      reaction.

PMID- 29073336
TI  - A review of methods for comparing treatments evaluated in studies that form
      disconnected networks of evidence.
AB  - A network meta-analysis allows a simultaneous comparison between treatments
      evaluated in randomised controlled trials that share at least one treatment with
      at least one other study. Estimates of treatment effects may be required for
      treatments across disconnected networks of evidence, which requires a different
      statistical approach and modelling assumptions to account for imbalances in
      prognostic variables and treatment effect modifiers between studies. In this
      paper, we review and discuss methods for comparing treatments evaluated in
      studies that form disconnected networks of evidence. Several methods have been
      proposed but assessing which are appropriate often depends on the clinical
      context as well as the availability of data. Most methods account for sampling
      variation but do not always account for others sources of uncertainty. We suggest
      that further research is required to assess the properties of methods and the use
      of approaches that allow the incorporation of external information to reflect
      parameter and structural uncertainty.

PMID- 29073337
TI  - Altered brain networks in psychogenic erectile dysfunction: a resting-state fMRI
      study.
AB  - Various neuroimaging studies had identified changes of cerebral activity and
      structures during the processes of sexual arousal. The identified brain regions
      were also believed to regulate emotional and cognitive processes. Yet, little was
      known about the neural mechanisms underlying psychogenic erectile dysfunction.
      Moreover, brain mechanisms mediating the processing of sexual arousal by these
      psychological processes were unclear. To investigate this issue, graph theory was
      applied to evaluate the topological properties of functional brain networks among
      24 psychogenic erectile dysfunction patients and 26 healthy controls. Abnormal
      metrics and correlations with clinical characteristics were further analyzed. Our
      results showed that psychogenic erectile dysfunction had higher small-worldness
      and more modules. Furthermore, psychogenic erectile dysfunction showed altered
      path length and strength of the right superior frontal gyrus (dorsolateral),
      superior parietal gyrus, parahippocampal gyrus and left temporal pole (superior
      temporal gyrus), post-central gyrus, mainly located in the cognitive control and
      emotional regulation subnetworks. And the altered parameters of the small
      worldness and right parahippocampal gyrus were related to the clinical
      characteristics of psychogenic erectile dysfunction. Together, our results
      suggested that psychogenic erectile dysfunction was associated with disruptions
      in the topological structure of functional brain subnetworks underlying the
      cognitive and emotional processes.

PMID- 29073339
TI  - Autism and primary care dentistry: parents' experiences of taking children with
      autism or working diagnosis of autism for dental examinations.
AB  - BACKGROUND: Accessing and receiving preventative dental treatment can be
      difficult for children with autism due to sensory processing disorders and/or
      challenging behaviours coupled with a reported reluctance by dentists to treat
      these children. AIM: To gather dental experiences of UK parents of children with
      autism or working diagnosis of autism and explore how they feel primary care
      dental services can be improved. DESIGN: A total of 17 parents of children with a
      diagnosis or working diagnosis of autism took part in semi-structured interviews.
      Data were analysed thematically. RESULTS: Key themes identified were flexibility
      of the dental team and environment, confidence of the parents to advocate for
      their children's needs, continuity of services and clear referral pathways to
      specialist services. Cross-cutting all themes was the value of clear
      communication. The experiences provide greater understanding of issues such as
      hyper-empathy, the dental chair, challenges of the waiting room, perceived
      medical authority, and the importance of continuation of care. CONCLUSION: In
      line with previous research about the importance of family-centred care, a strong
      relationship between parents and the whole dental team is essential for children
      with autism to access dental examinations and have satisfactory experience of
      care.

PMID- 29073338
TI  - Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine
      epithelium, but not epidermis.
AB  - Stem Leydig cells (SLCs), precursors of testicular Leydig cells that secrete
      testosterone required for male sexual differentiation, spermatogenesis, and
      fertility, were recently identified in rat testes. Various types of stem cells
      have shown the ability to differentiate into other tissues, but there is no
      information on the plasticity of adult rat SLCs (rSLCs). This study investigated
      the ability of rSLCs to transdifferentiate into cell types from all three germ
      layers-prostatic epithelium (endoderm), uterine epithelium (mesoderm), and
      epidermis (ectoderm)-under the influence of inductive mesenchyme from fetal and
      neonatal tissues. To differentiate rSLCs into cells of other lineages, mesenchyme
      from green fluorescent protein (GFP)-expressing mice was used. Tissue
      recombinants of urogenital sinus mesenchyme (a potent prostate inducer) and rSLCs
      grafted into adult male hosts formed ductal structures resembling prostate after
      5 weeks. Prostate epithelium was of rSLC origin as determined by absence of GFP
      expression, and expressed characteristic markers of prostatic epithelium.
      Similarly, uterine mesenchyme + rSLCs tissue recombinants contained a simple
      columnar epithelium that was histologically similar to normal uterine epithelium
      and expressed typical uterine epithelial markers, but was of rSLC origin. In
      contrast, epidermal tissue was absent in fetal dermis + rSLCs recombinants,
      suggesting rSLCs did not form skin epithelium. Thus, rSLCs can transdifferentiate
      into uterine and prostatic epithelium, mesodermal, and endodermal derivatives,
      respectively, but they may have a limited transdifferentiation potential, as
      shown by their inability to form epidermis, an ectodermal derivative.

PMID- 29073341
TI  - Metabolomics toward personalized medicine.
AB  - Metabolomics, which is the metabolites profiling in biological matrices, is a key
      tool for biomarker discovery and personalized medicine and has great potential to
      elucidate the ultimate product of the genomic processes. Over the last decade,
      metabolomics studies have identified several relevant biomarkers involved in
      complex clinical phenotypes using diverse biological systems. Most diseases
      result in signature metabolic profiles that reflect the sums of external and
      internal cellular activities. Metabolomics has a major role in clinical practice
      as it represents >95% of the workload in clinical laboratories worldwide. Many of
      these metabolites require different analytical platforms, such as Nuclear
      Magnetic Resonance (NMR), Mass Spectrometry (MS), and Ultra Performance Liquid
      Chromatography (UPLC), while many clinically relevant metabolites are still not
      routinely amenable to detection using currently available assays. Combining
      metabolomics with genomics, transcriptomics, and proteomics studies will result
      in a significantly improved understanding of the disease mechanisms and the
      pathophysiology of the target clinical phenotype. This comprehensive approach
      will represent a major step forward toward providing precision medical care, in
      which individual is accounted for variability in genes, environment, and personal
      lifestyle. In this review, we compare and evaluate the metabolomics strategies
      and studies that focus on the discovery of biomarkers that have "personalized"
      diagnostic, prognostic, and therapeutic value, validated for monitoring disease
      progression and responses to various management regimens.

PMID- 29073340
TI  - Liver-Targeted Small-Molecule Inhibitors of Proprotein Convertase
      Subtilisin/Kexin Type 9 Synthesis.
AB  - Targeting of the human ribosome is an unprecedented therapeutic modality with a
      genome-wide selectivity challenge. A liver-targeted drug candidate is described
      that inhibits ribosomal synthesis of PCSK9, a lipid regulator considered
      undruggable by small molecules. Key to the concept was the identification of
      pharmacologically active zwitterions designed to be retained in the liver. Oral
      delivery of the poorly permeable zwitterions was achieved by prodrugs susceptible
      to cleavage by carboxylesterase 1. The synthesis of select tetrazole prodrugs was
      crucial. A cell-free in vitro translation assay containing human cell lysate and
      purified target mRNA fused to a reporter was used to identify active zwitterions.
      In vivo PCSK9 lowering by oral dosing of the candidate prodrug and quantification
      of the drug fraction delivered to the liver utilizing an oral positron emission
      tomography 18 F-isotopologue validated our liver-targeting approach.

PMID- 29073342
TI  - Antibacterial Narrow-Band-Gap Conjugated Oligoelectrolytes with High Photothermal
      Conversion Efficiency.
AB  - Two conjugated oligoelectrolytes (COEs), WMG1 and WMG2, were designed with the
      goal of achieving near infrared absorption and high photothermal conversion
      efficiency. Specifically, electron-rich thiophene and electron-poor benzo[1,2
      c:4,5-c']bis[1,2,5]thiadiazole subunits were introduced into the conjugated core
      to modulate the optical gap and to reduce the fluorescence emission efficiency.
      WMG1 and WMG2 show absorption maxima at around 800 nm, which favors tissue
      penetration. Although relatively small in size, WMG1 and WMG2 exhibit
      photothermal conversion efficiencies of circa 60 % and 54 %, respectively. WMG1
      shows dark toxicity to the Gram positive bacterium B. subtilis and good
      photothermal killing efficiency toward both B. subtilis and Gram negative E.
      coli, features that demonstrate the promising potential of the COE molecular
      design for photothermal applications.

PMID- 29073343
TI  - Prevalence and Disease-Specific Risk Factors for Lower Urinary Tract Symptoms in
      Systemic Sclerosis: An International Multicenter Study.
AB  - OBJECTIVE: To determine the prevalence of lower urinary tract symptoms (LUTS) in
      systemic sclerosis (SSc), to find specific risk factors, and to assess their
      impact on quality of life (QoL). METHODS: In a multicenter study, 334 patients
      completed a self-administered questionnaire on LUTS and QoL. LUTS were classified
      into 3 main categories: storage, voiding, and post-micturition symptoms.
      Digestive symptoms burden was captured by a visual analog scale, divided into 5
      equal categories. Multivariable logistic regressions were performed to test
      association between risk factors and LUTS categories. Linear regression adjusted
      the association between LUTS and QoL. RESULTS: LUTS were recorded in 311 SSc
      patients (96.0%) and classified as severe in 120 (38.0%). The storage category of
      LUTS was the most prevalent (91.9%), followed by voiding (72.2%) and then by post
      micturition symptoms (49.8%). Risk factors identified in the multivariable models
      were higher than the median Health Assessment Questionnaire disability index (HAQ
      DI; odds ratio [OR] 4.2 [95% confidence interval (95% CI) 1.4-12.9]) in the
      storage category; higher than the median HAQ DI (OR 2.4 [95% CI 1.2-4.9]) for
      digestive symptoms burden (OR 1.9 [95% CI 1.3-2.7]) and synovitis (OR 4.8 [95% CI
      1.0-22.6) in the voiding category; and higher for digestive symptoms burden (OR
      1.2 [95% CI 1.0-1.5]) in the post-micturition category of symptoms. These factors
      also increased the odds of having further severe symptoms. QoL was affected by
      the 3 categories of LUTS and decreased progressively with increasing frequency of
      symptoms. CONCLUSION: Self-reported LUTS are among the most frequent symptoms in
      SSc and are associated with digestive symptoms. SSc patients with LUTS have lower
      QoL.

PMID- 29073344
TI  - Similarities and Differences in the Functions of Nonsuicidal Self-Injury (NSSI)
      and Sex as Self-Injury (SASI).
AB  - Differences and similarities were studied in the functions of two different self
      injurious behaviors (SIB): nonsuicidal self-injury (NSSI) and sex as self-injury
      (SASI). Based on type of SIB reported, adolescents were classified in one of
      three groups: NSSI only (n = 910), SASI only (n = 41), and both NSSI and SASI (n
      = 76). There was support for functional equivalence in the two forms of SIB, with
      automatic functions being most commonly endorsed in all three groups. There were
      also functional differences, with adolescents in the SASI only group reporting
      more social influence functions than those with NSSI only. Adolescents reporting
      both NSSI and SASI endorsed the highest number of functions for both behaviors.
      Clinical implications are discussed, emphasizing the need for emotion regulation
      skills.

PMID- 29073345
TI  - Interpreting the Chinese version of quality of life questionnaire for functional
      digestive disorders.
AB  - BACKGROUND AND AIM: The Chinese version quality of life questionnaire for
      functional digestive disorders (Chin-FDDQL) is a useful health assessment
      instrument for functional dyspepsia. This study aims to identify its score
      interpretation for clinical practice. METHODS: Data of Chin-FDDQL from the
      functional dyspepsia patients (>= 18 years) between November 2009 and April 2013
      were enrolled in the 1st and 14th day. After baseline and responsiveness
      analysis, the single score interpretation and percentile ranks were established.
      The statistically reliable change was defined with effect size, standardized
      response mean, minimal detectable change, and others. Then the receiver operating
      characteristic curve analysis for health improvement was performed to define the
      clinically important change. RESULTS: Two hundred two functional dyspepsia
      patients, 150 healthy participants, and 25 missing data were enrolled for
      analysis. Compared with the intake patients, the discharged and healthy persons
      have significant better health status in all domains (P < 0.001, expect
      discomfort in discharged people, P = 0.142), totally contrast to missing data.
      The reliability for single total intake and discharge were both +/- 1. Based on
      score distribution, the 25th, 50th, and 75th percentile ranks were 49, 58, and 66
      for intake scores and 59, 65, and 72 for discharge scores, respectively. The
      minimal detectable change and Reliable Change Index were 6 and 11 for total
      score. Receiver operating characteristic analyses supported that total score
      changes 4 or more represented minimal clinically important improvement.
      CONCLUSIONS: The score interpretation system of the Chin-FDDQL could assist
      clinician's decision making during the therapy practice.

PMID- 29073346
TI  - Direct Determination of Electron-Transfer Properties of Dicopper-Bound Reduced
      Dioxygen Species by a Cryo-Spectroelectrochemical Approach.
AB  - Direct experimental determination of redox properties of superoxo (O2.- ) and
      peroxo (O22- ) embedded in dicopper complexes bearing an unsymmetrical
      binucleating ligand was achieved using cryo-electrochemistry and cryo
      spectroelectrochemistry in dichloromethane. Cyclic voltammetry for dicopper(I)
      (1+ ) oxidation to a CuI CuII mixed-valent species (12+ ) under inert atmosphere
      at 193 K reveals slow heterogeneous electron-transfer kinetics, indicative of a
      large reorganization energy. Oxygenation of the dicuprous complex 1+ gives the
      bridged peroxo dicopper(II) species 3+ , which is reversibly oxidized to the
      superoxo complex 22+ at E0 =0.11 V (vs. SCE) with a small inner sphere electron
      transfer reorganization energy, lambdai =0.54 eV, determined from variable
      temperature electrochemical impedance spectroscopy. The data suggest that the O2.
      /O22- redox process occurs directly on the O2 -derived core.

PMID- 29073347
TI  - Efficacy and Safety of Atacicept in Patients With Systemic Lupus Erythematosus:
      Results of a Twenty-Four-Week, Multicenter, Randomized, Double-Blind, Placebo
      Controlled, Parallel-Arm, Phase IIb Study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of atacicept, an antagonist of B
      lymphocyte stimulator/APRIL-mediated B cell activation, in patients with systemic
      lupus erythematosus (SLE). METHODS: ADDRESS II is a 24-week, multicenter,
      randomized, double-blind, placebo-controlled, parallel-arm, phase IIb study
      evaluating the safety and efficacy of atacicept in patients with SLE
      (ClinicalTrials.gov identifier NCT01972568). Patients with active, autoantibody
      positive SLE receiving standard therapy were randomized (1:1:1) to receive
      atacicept (75 mg or 150 mg) or placebo for 24 weeks. The primary end point was
      the SLE responder index 4 (SRI-4) at week 24. RESULTS: The intent-to-treat (ITT)
      population included 306 patients. There was a trend toward an improved SRI-4
      response rate with atacicept 75 mg (57.8%; adjusted odds ratio [OR] 1.78, P =
      0.045) and 150 mg (53.8%; adjusted OR 1.56, P = 0.121) at week 24 as compared
      with placebo (44.0%) (primary analysis; using the screening visit as baseline).
      In a prespecified sensitivity analysis using study day 1 as baseline, a
      significantly larger proportion of patients receiving atacicept 75 mg and 150 mg
      achieved an SRI-4 response at week 24 compared with placebo. In predefined
      subpopulations with high levels of disease activity (HDA) at baseline,
      serologically active disease, or both, statistically significant improvements in
      the SRI-4 and SRI-6 response rates were seen with atacicept versus placebo. A
      severe risk of disease flare was reduced with atacicept therapy in both the ITT
      and the HDA populations. The risks of serious adverse events and serious or
      severe infection were not increased with atacicept as compared with placebo.
      CONCLUSION: Atacicept treatment showed evidence of efficacy in SLE, particularly
      in HDA and serologically active patients. Reductions in disease activity and
      severe flare were observed with atacicept treatment, with an acceptable safety
      profile.

PMID- 29073349
TI  - Association Between Dose of Glucocorticoids and Coronary Artery Lesions in
      Kawasaki Disease.
AB  - OBJECTIVE: Several studies revealed the efficacy of glucocorticoids on prevention
      of coronary artery lesions (CALs) in Kawasaki disease (KD) patients. However,
      impacts of different doses of glucocorticoids on clinical outcomes of KD remain
      unknown. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient
      database, we evaluated KD patients who were treated with normal-dose
      (prednisolone 0.5-4.0 mg/kg/day) or high-dose (methylprednisolone 10-40
      mg/kg/day) glucocorticoids. We investigated risks of CALs and readmission, total
      hospitalization cost, and length of hospital stay in the acute phase of KD using
      propensity score matching, stabilized propensity-score inverse probability of
      treatment weighting, and instrumental variable methods. RESULTS: We identified a
      total of 3,220 patients with KD who were treated with normal-dose (n = 2,453) or
      high-dose (n = 767) glucocorticoids in addition to intravenous immunoglobulin.
      One-to-one propensity-matched analyses with 744 pairs demonstrated no significant
      differences between the normal-dose and the high-dose groups in risk of CALs
      (risk ratio [RR] 0.83, 95% confidence interval [95% CI] 0.49, 1.40) and risk of
      readmissions (RR 0.85, 95% CI 0.65, 1.11). Stabilized propensity-score inverse
      probability weighting and instrumental variable analyses showed similar results
      to the propensity score matching analyses. CONCLUSION: Risks of CALs and
      readmissions and total hospitalization costs were similar between the normal-dose
      and the high-dose glucocorticoids groups for patients with KD, whereas total
      length of hospital stay was shorter in the high-dose group than that in the
      normal-dose group.

PMID- 29073350
TI  - Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus
      Erythematosus and Neuromyelitis Optica Spectrum Disorder: Do They Share Common
      Targets?
AB  - OBJECTIVE: IgG anti-DWEYS antibodies cross-reactive with DNA and the N-methyl-d
      aspartate receptor subunits GluN2A and GluN2B are known to be associated with
      neuropsychiatric systemic lupus erythematosus (NPSLE). IgG anti-DWEYS have not
      been investigated in demyelinating NPSLE or in another demyelinating disorder,
      neuromyelitis optica spectrum disorder (NMOSD), which is a disease also found
      mainly in young women and associated with aquaporin 4 (AQP-4) or myelin
      oligodendrocyte glycoprotein (MOG) antibodies. This study was undertaken to
      investigate the frequency of all of these brain-reactive antibodies in patients
      with NPSLE, those with demyelinating NPSLE, and those with NMOSD. METHODS: Serum
      samples from patients with NPSLE (n = 108), patients with SLE without
      neuropsychiatric manifestations (n = 38), patients with NMOSD (n = 33), and
      healthy controls (n = 106) were assessed for the frequency of IgG anti-brain
      antibodies as well as IgG antibodies to AQP-4, MOG, GluN2A/GluN2B, and double
      stranded DNA (dsDNA). RESULTS: Sera were positive for IgG anti-AQP-4 antibodies
      in 27 (82%) of 33 patients with NMOSD and 3 (27%) of 11 patients with
      demyelinating NPSLE, whereas all sera from patients with non-demyelinating NPSLE,
      patients with SLE, and healthy controls were negative for IgG anti-AQP-4. IgG
      anti-MOG were detected at high titers in 3 (50%) of 6 patients with NMOSD who
      were negative for IgG anti-AQP-4, and at low titers in 2 (18%) of 11 patients
      with demyelinating NPSLE and 1 (1%) of 97 patients with non-demyelinating NPSLE.
      IgG antibodies to dsDNA were present in 11 (33%) of 33 patients with NMOSD. Only
      4 (12%) of 33 patients with NMOSD were positive for IgG anti-DWEYS, compared to
      11 (29%) of 38 patients with SLE and 59 (55%) of 108 patients with NPSLE. IgG
      anti-DWEYS antibodies were present in 56 (58%) of 97 patients with non
      demyelinating NPSLE and 3 (27%) of 11 patients with demyelinating NPSLE. Serum
      IgG brain-reactive antibodies were present at a similar frequency in patients
      with non-demyelinating NPSLE (72 [75%] of 96), those with demyelinating NPSLE (9
      [82%] of 11), and those with SLE (32 [84%] of 38), but were less frequent in
      patients with NMOSD (20 [61%] of 33). CONCLUSION: Patients with demyelinating
      NPSLE should be tested for IgG antibodies to AQP-4, MOG, and DWEYS. IgG anti-AQP
      4 can be considered diagnostic for NMOSD, whereas none of these antibodies appear
      to be diagnostic for demyelinating NPSLE. Moreover, IgG anti-dsDNA are present in
      patients with NMOSD but are not cross-reactive with IgG anti-DWEYS, indicating
      that the antigenic stimulus and mechanisms of tissue damage are potentially
      different between demyelinating NPSLE and NMOSD.

PMID- 29073348
TI  - Gut Microbiota Perturbations in Reactive Arthritis and Postinfectious
      Spondyloarthritis.
AB  - OBJECTIVE: Reactive arthritis (ReA) is an inflammatory disorder occurring several
      weeks after gastrointestinal or genitourinary tract infections. HLA-B27
      positivity is considered a risk factor, although it is not necessarily predictive
      of disease incidence. Among nongenetic factors, the intestinal microbiome may
      play a role in disease susceptibility. The objective of this study was to
      characterize the gut microbiota and host gene interactions in ReA and
      postinfectious spondyloarthritis. METHODS: Adult subjects with peripheral
      spondyloarthritis and control subjects with preceding infections who did not
      develop arthritis were prospectively recruited from a geographic region with a
      high prevalence of ReA. Clinical variables, HLA status, and 16S ribosomal RNA
      gene sequencing of intestinal microbiota were analyzed. RESULTS: Subjects with
      ReA showed no significant differences from controls in gut bacterial richness or
      diversity. However, there was a significantly higher abundance of Erwinia and
      Pseudomonas and an increased prevalence of typical enteropathogens associated
      with ReA. Subjects with ultrasound evidence of enthesitis were enriched in
      Campylobacter, while subjects with uveitis and radiographic sacroiliitis were
      enriched in Erwinia and unclassified Ruminococcaceae, respectively; both were
      enriched in Dialister. Host genetics, particularly HLA-A24, were associated with
      differences in gut microbiota diversity irrespective of disease status. We
      identified several co-occurring taxa that were also predictive of HLA-A24 status.
      CONCLUSION: This is the first culture-independent study characterizing the gut
      microbial community in postinfectious arthritis. Although bacterial factors
      correlated with disease presence and clinical features of ReA, host genetics also
      appeared to be a major independent driver of intestinal community composition.
      Understanding of these gut microbiota-host genetic relationships may further
      clarify the pathogenesis of postinfectious spondyloarthritides.

PMID- 29073351
TI  - Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a
      Randomized, Double-Blind, Placebo-Controlled, Pilot Trial.
AB  - OBJECTIVE: To assess the safety and efficacy of treatment with belimumab in
      patients with early diffuse cutaneous systemic sclerosis (dcSSc) treated with
      background mycophenolate mofetil (MMF). METHODS: In this 52-week, investigator
      initiated, single-center, double-blind, placebo-controlled, pilot study, 20
      patients with dcSSc recently started on MMF were randomized 1:1 to additionally
      receive belimumab at 10 mg/kg intravenously or placebo. We assessed safety,
      efficacy, and differential gene expression. RESULTS: In the belimumab group, the
      median modified Rodnan skin thickness score (MRSS) decreased from 27
      (interquartile range [IQR] 26.5, 31) to 18 (IQR 11, 23) (P = 0.039). In the
      placebo group, the median MRSS decreased from 28 (IQR 22, 28) to 21 (IQR 14, 25)
      (P = 0.023). The median change in MRSS was -10 (IQR -13, -9) in the belimumab
      group and -3.0 (IQR -15, -1) in the placebo group (P = 0.411). There were no
      significant differences between the groups in the number of adverse events (AEs).
      A significant decrease in expression of B cell signaling and profibrotic genes
      and pathways was observed in patients with improved MRSS in the belimumab group
      but not in the placebo group. CONCLUSION: Patients in both treatment groups
      experienced significant improvements in MRSS. The median difference was greater
      in the belimumab group but did not achieve statistical significance in this small
      pilot study. AEs were similar between the groups. Changes in gene expression were
      consistent with mechanism of action and showed that clinical response to
      treatment with belimumab is associated with a significant decrease in profibrotic
      genes and pathways. Additional studies are needed to determine the role of
      belimumab in the treatment of dcSSc.

PMID- 29073352
TI  - Accumulation of Antigen-Driven Lymphoproliferations in Complement Receptor 2/CD21
      /low B Cells From Patients With Sjogren's Syndrome.
AB  - OBJECTIVE: Patients with Sjogren's syndrome (SS) are prone to develop malignant
      lymphomas, and a correlation has been established between the
      lymphoproliferations occurring in these disorders and the presence in patients'
      blood of an unusual B cell population that down-regulates complement receptor
      2/CD21. This study was undertaken to identify the B cell compartment from which
      these lymphoproliferations emerge and determine the mechanisms that promote
      clonal B cell expansion in patients with SS. METHODS: The reactivity of
      antibodies expressed by CD19+CD10-CD27-IgM+CD21-/low cells isolated from the
      blood of patients with SS was tested using a polymerase chain reaction-based
      approach that allows us to clone and express, in vitro, recombinant antibodies
      produced by single B cells. RESULTS: Clonal expansions were identified in CD21
      /low B cells isolated from the peripheral blood of 3 patients with SS. These
      lymphoproliferations expressed B cell receptors (BCRs) that displayed somatic
      hypermutation lineage trees characteristic of a strong selection by antigens; one
      of these antigens was identified as a ribosomal self antigen. When the mutated
      BCR sequences expressed by the expanded CD21-/low B cell clones from patients
      with SS were reverted in vitro to their germline counterparts, one clone remained
      autoreactive. CONCLUSION: Clonal lymphoproliferations in patients with SS
      preferentially accumulate in the autoreactive CD21-/low B cell compartment often
      expanded in these subjects, and recognition of self antigens may drive the clonal
      B cell expansion while further refining BCR self-reactivity.

PMID- 29073353
TI  - Trial Characteristics as Contextual Factors When Evaluating Targeted Therapies in
      Patients With Psoriatic Disease: A Meta-Epidemiologic Study.
AB  - OBJECTIVE: To assess the importance of trial characteristics as contextual
      factors when evaluating the treatment effect of targeted therapies for patients
      with psoriatic disease. METHODS: We identified randomized controlled trials
      (RCTs) evaluating targeted therapies approved for psoriatic arthritis (PsA) and
      psoriasis (8 biologics and apremilast). The effect of targeted therapies was
      analyzed in the 2 psoriatic conditions combined by using drug retention as a
      common outcome, and separately by using the American College of Rheumatology 20%
      improvement criteria (ACR20) for PsA and the Psoriasis Area Severity Index 75%
      improvement score (PASI75) for psoriasis. We explored potential effect
      modification of trial characteristics in stratified and meta-regression analyses.
      Odds ratios (ORs) were calculated and compared among the trial eligibility
      criteria via the ratio of ORs. RESULTS: Forty-eight PsA and psoriasis trials (51
      comparisons; 17,737 patients) were eligible. Overall retention was OR 2.16 (95%
      confidence interval [95% CI] 1.70-2.75) with higher odds for PsA trials compared
      with psoriasis trials (ratio of ORs 2.55 [95% CI 1.64-3.97]). The eligibility
      criteria "targeted therapy history," "minimum required disease duration,"
      "required negative rheumatoid factor," and "required Classification Criteria for
      Psoriatic Arthritis criteria" were of importance for achieving ACR20 in PsA. The
      eligibility criterion "minimum required disease duration" was of importance for
      achieving PASI75 in psoriasis. A total of 7 PsA trials had rescue before time
      point-of-retention reporting (adaptive trials). CONCLUSION: From this exploratory
      meta-epidemiologic study, we now have evidence from RCTs to support the notion
      that patients with PsA are more likely to adhere to targeted therapies compared
      to patients with psoriasis. Furthermore, we identified a few contextual factors
      of importance in regard to achieving ACR20 in PsA trials and PASI75 in psoriasis
      trials.

PMID- 29073354
TI  - Oral Administration of Vanillin Improves Imiquimod-Induced Psoriatic Skin
      Inflammation in Mice.
AB  - Vanillin is one of the most widely used flavoring products worldwide. Psoriasis
      is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin
      17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect
      of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice
      were treated topically with IMQ on the back skin and orally with various amounts
      of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced
      histopathological changes of skin in a dose-dependent manner. The thickness and
      number of cell layers of epidermis were reduced by 29 +/- 14.4 and 27.8 +/- 11%,
      respectively, in mice given 100 mg/kg of vanillin. A microarray showed that a
      total of 9042 IMQ-upregulated genes were downregulated by vanillin, and the
      biological pathways involved in the immune system and metabolism were
      significantly altered by vanillin. The upregulated expressions of IL-23, IL-17A,
      and IL-17F genes were suppressed by vanillin, with fold changes of -3.07 +/-
      0.08, -2.06 +/- 0.21, and -1.62 +/- 0.21, respectively. Moreover, vanillin
      significantly decreased both the amounts of IL-17A and IL-23 and the infiltration
      of immune cells in the skin tissues of IMQ-treated mice. In conclusion, our
      findings suggested that vanillin was an effective bioactive compound against
      psoriatic skin inflammation. Moreover, the downregulation of IL-23 and IL-17
      expression suggested that vanillin was a novel regulator of the IL-23/IL-17 axis.

PMID- 29073355
TI  - How Bound and Free Fatty Acids in Cellulose Films Impact Nonspecific Protein
      Adsorption.
AB  - The effect of fatty acids and fatty acid esters to impair nonspecific protein
      adsorption on cellulose thin films is investigated. Thin films are prepared by
      blending trimethylsilyl cellulose solutions with either cellulose stearoyl ester
      or stearic acid at various ratios. After film formation by spin coating, the
      trimethylsilyl cellulose fraction of the films is converted to cellulose by
      exposure to HCl vapors. The morphologies and surface roughness of the blends were
      examined by atomic force microscopy revealing different feature shapes and sizes
      depending on the blend ratios. Nonspecific protein adsorption at the example of
      bovine serum albumin toward the blend thin films was tested by means of surface
      plasmon resonance spectroscopy in real-time. Incorporation of stearic acid into
      the cellulose leads to highly protein repellent surfaces regardless of the amount
      added. The stearic acid acts as a sacrificial compound that builds a complex with
      bovine serum albumin thereby inhibiting protein adsorption. For the blends where
      stearoyl ester is added to the cellulose films, the cellulose:cellulose stearoyl
      ester ratios of 3:1 and 1:1 lead to much lower nonspecific protein adsorption
      compared to pure cellulose, whereas for the other ratios, adsorption increases.
      Supplementary results were obtained from atomic force microscopy experiments
      performed in liquid during exposure to protein solution and surface free energy
      determinations.

PMID- 29073356
TI  - Microfluidic System for Detection of Viral RNA in Blood Using a Barcode
      Fluorescence Reporter and a Photocleavable Capture Probe.
AB  - A microfluidic sample preparation multiplexer (SPM) and assay procedure is
      developed to improve amplification-free detection of Ebola virus RNA from blood.
      While a previous prototype successfully detected viral RNA following off-chip RNA
      extraction from infected cells, the new device and protocol can detect Ebola
      virus in raw blood with clinically relevant sensitivity. The Ebola RNA is
      hybridized with sequence specific capture and labeling DNA probes in solution and
      then the complex is pulled down onto capture beads for purification and
      concentration. After washing, the captured RNA target is released by irradiating
      the photocleavable DNA capture probe with ultraviolet (UV) light. The released,
      labeled, and purified RNA is detected by a sensitive and compact fluorometer.
      Exploiting these capabilities, a detection limit of 800 attomolar (aM) is
      achieved without target amplification. The new SPM can run up to 80 assays in
      parallel using a pneumatic multiplexing architecture. Importantly, our new
      protocol does not require time-consuming and problematic off-chip probe
      conjugation and washing. This improved SPM and labeling protocol is an important
      step toward a useful POC device and assay.

PMID- 29073357
TI  - Luciferase Activity of Insect Fatty Acyl-CoA Synthetases with Synthetic
      Luciferins.
AB  - Long-chain fatty acyl-CoA synthetases (ACSLs) are homologues of firefly
      luciferase but are incapable of emitting light with firefly luciferin. Recently,
      we found that an ACSL from the fruit fly Drosophila melanogaster is a latent
      luciferase that will emit light with the synthetic luciferin CycLuc2. Here, we
      have profiled a panel of three insect ACSLs with a palette of >20 luciferin
      analogues. An ACSL from the nonluminescent beetle Agrypnus binodulus (AbLL) was
      found to be a second latent luciferase with distinct substrate specificity.
      Several rigid luciferins emit light with both ACSLs, but styryl luciferin
      analogues are light-emitting substrates only for AbLL. On the other hand, an ACSL
      from the luminescent beetle Pyrophorus angustus lacks luciferase activity with
      all tested analogues, despite its higher homology to beetle luciferases. Further
      study of ACSLs is expected to shed light on the features necessary for
      bioluminescence and substrate selectivity.

PMID- 29073358
TI  - Control the Structure of Zr-Tetracarboxylate Frameworks through Steric Tuning.
AB  - Ligands with flexible conformations add to the structural diversity of metal
      organic frameworks but, at the same time, pose a challenge to structural design
      and prediction. Representative examples include Zr-tetracarboxylate-based MOFs,
      which afford assorted structures for a wide range of applications, but also
      complicate the structural control. Herein, we systematically studied the
      formation mechanism of a series of (4,8)-connected Zr-tetracarboxylate-based MOFs
      by altering the substituents on different positions of the organic linkers.
      Different ligand rotamers give rise to three types of structures with flu, scu,
      and csq topologies. A combination of experiment and molecular simulation indicate
      that the steric hindrance of the substituents at different positions dictates the
      resulting MOF structures. Additionally, the controllable formation of different
      structures was successfully implemented by a combination of linkers with
      different steric effects at specific positions.

PMID- 29073359
TI  - Complete genome sequence of Enterobacter cloacae R11 reveals multiple genes
      potentially associated with high-level polymyxin E resistance.
AB  - Enterobacter cloacae strain R11 is a multidrug-resistant bacterium isolated from
      sewage water near a swine feedlot in China. Strain R11 can survive in medium
      containing up to 192 MUg/mL polymyxin E, indicating a tolerance for this
      antibiotic that is significantly higher than that reported for other gram
      negative bacteria. In this study, conjugation experiments showed that partial
      polymyxin E resistance could be transferred from strain R11 to Escherichia coli
      strain 25922, revealing that some genes related to polymyxin E resistance are
      plasmid-based. The complete genome sequence of this strain was determined,
      yielding a total of 4 993 008 bp (G+C content, 53.15%) and 4908 genes for the
      circular chromosome and 4 circular plasmids. Genome analysis revealed a total of
      73 putative antibiotic resistance genes, including several polymyxin E resistance
      genes and genes potentially involved in multidrug resistance. These data provide
      insights into the genetic basis of the polymyxin E resistance and multidrug
      resistance of E. cloacae.

PMID- 29073360
TI  - Modeling Radiation Effects of Ultrasoft X Rays on the Basis of Amorphous Track
      Structure.
AB  - There is experimental evidence that ultrasoft X rays (0.1-5 keV) show a higher
      biological effectiveness than high-energy photons. Similar to high-LET radiation,
      this is attributed to a rather localized dose distribution associated with a
      considerably smaller range of secondary electrons, which results in an increasing
      yield of double-strand breaks (DSBs) and potentially more complex lesions. We
      previously reported on the application of the Giant LOop Binary LEsion (GLOBLE)
      model to ultrasoft X rays, in which experimental values of the relative
      biological effectiveness (RBE) for DSB induction were used to show that this
      increasing DSB yield was sufficient to explain the enhanced effectiveness in the
      cell inactivation potential of ultrasoft X rays. Complementary to GLOBLE, we
      report here on a modeling approach to predict the increased DSB yield of
      ultrasoft X rays on the basis of amorphous track structure formed by secondary
      electrons, which was derived from Monte Carlo track structure simulations. This
      procedure is associated with increased production of single-strand break (SSB)
      clusters, which are caused by the highly localized energy deposition pattern
      induced by low-energy photons. From this, the RBE of ultrasoft X rays can be
      determined and compared to experimental data, showing that the inhomogeneity of
      the energy deposition pattern represents the key variable to describe the
      increased biological effectiveness of ultrasoft X rays. Thus, this work
      demonstrates an extended applicability of the amorphous track structure concept
      and tests its limits with respect to its predictive power. The employed model
      mechanism offers a possible explanation for how the cellular response to
      ultrasoft X rays is directly linked to the energy deposition properties on the
      nanometric scale.

PMID- 29073362
TI  - Effectiveness of Contour Augmentation with Guided Bone Regeneration: 10-Year
      Results.
AB  - In aesthetic sites, the integrity of the facial bone wall dimension in the
      anterior maxilla is jeopardized by physiologic and structural changes
      postextraction. An effective regenerative protocol is key to reestablish and
      maintain the hard and soft tissue dimensions over time. The present prospective
      case series study examined the effectiveness of early implant placement with
      simultaneous contour augmentation through guided bone regeneration with a 2-layer
      composite graft in postextraction single-tooth sites over an observation period
      of 10 y among 20 patients. The median peri-implant bone loss was 0.35 mm between
      the 1- and 10-y examination. A success rate of 95% was obtained, with pleasing
      aesthetic outcomes and a high median Pink Esthetic Score (8). Implant crowns
      (ICs) revealed significant median facial recession between IC10y and IC1y (0.17
      mm). The facial bone wall dimensions were assessed by preoperative cone beam
      computed tomography and 2 subsequent scans taken at 6 and 10 y. The median facial
      bone wall thickness increased significantly from 0 mm at surgery to 1.67 mm at
      the 10-y examination. The facial vertical bone wall peak (DIC) was located at a
      median distance of 0.16 mm coronal to the implant shoulder. The facial vertical
      bone loss of DIC amounted to 0.02 mm between 6 and 10 y. Equivalence testing was
      performed for the null hypothesis of a difference of >0.2 mm per year between 2
      respective time points, showing stable bone conditions. Modulating factors
      influencing the regenerative outcomes at 10 y were the preoperative proximal
      crest width and soft tissue thickness. In conclusion, the present study confirmed
      the long-term effectiveness of early implant placement with simultaneous contour
      augmentation through guided bone regeneration with a 2-layer composite graft in
      postextraction single-tooth sites offering stable bone conditions with low risks
      of mucosal recessions over an observation period of 10 y ( ClinicalTrials.gov
      NCT03252106).

PMID- 29073361
TI  - High-Risk Sarcoidosis. Current Concepts and Research Imperatives.
AB  - Sarcoidosis is a disease with heterogeneous manifestations and outcomes, varying
      in part on the basis of organ involvement. Specifically, patients with
      sarcoidosis at risk for poor outcomes include individuals with treatment
      resistant pulmonary sarcoidosis, including fibrotic pulmonary disease and
      pulmonary hypertension, as well as those with cardiac, neurologic, and multiorgan
      disease. The limited but available data relating to these patients with high-risk
      sarcoidosis, defined as those patients with presentations requiring medical
      intervention to avoid progressive disability or premature death, was evaluated as
      part of the National Heart, Lung, and Blood Institute's workshop to improve
      understanding of these disease manifestations. In particular, knowledge gaps that
      preclude a greater understanding of the pathogenesis and management of these
      severe sarcoidosis clinical phenotypes were identified in the workshop. Research
      strategies are proposed to address critical knowledge gaps that would further our
      understanding of these disease manifestations and enhance the care of these
      patients.

PMID- 29073363
TI  - Selective Role of Discoidin Domain Receptor 2 in Murine Temporomandibular Joint
      Development and Aging.
AB  - Temporomandibular joint (TMJ) disorders are often associated with development of
      osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor
      2 (DDR2), a collagen receptor preferentially activated by type I and III collagen
      found in the TMJ and other fibrocartilages, has been associated with TMJ
      degeneration, but its role in normal joint development has not been previously
      examined. Using Ddr2 LacZ-tagged mice and immunohistochemistry, we found that
      DDR2 is preferentially expressed and activated in the articular zone of TMJs but
      not knee joints. To assess the requirement for Ddr2 in TMJ development, studies
      were undertaken to compare wild-type and smallie ( slie) mice, which contain a
      spontaneous deletion in Ddr2 to produce an effective null allele. Analysis of
      TMJs from newborn Ddr2slie/slie mice revealed a developmental delay in condyle
      mineralization, as measured by micro-computed tomography and histologic analysis.
      In marked contrast, knee joints of Ddr2slie/slie mice were normal. Analysis of
      older Ddr2slie/slie mice (3 and 10 mo) revealed that the early developmental
      delay led to a dramatic and progressive loss of TMJ articular integrity and
      osteoarthritis-like changes. Mutant condyles had a rough and flattened bone
      surface, accompanied by a dramatic loss of bone mineral density. Mankin scores
      showed significantly greater degenerative changes in the TMJs of 3- and 10-mo-old
      Ddr2slie/slie mice as compared with wild-type controls. No DDR2-dependent
      degenerative changes were seen in knees. Analysis of primary cultures of TMJ
      articular chondrocytes from wild-type and Ddr2slie/slie mice showed defects in
      chondrocyte maturation and mineralization in the absence of Ddr2. These studies
      demonstrate that DDR2 is necessary for normal TMJ condyle development and
      homeostasis and that these DDR2 functions are restricted to TMJ fibrocartilage
      and not seen in the hyaline cartilage of the knee.

PMID- 29073365
TI  - Energy expenditure during an exercise training session for cardiac patients.
AB  - Increasing energy expenditure (EE) in cardiac patients remains a challenge.
      Exercise approaches in cardiac rehabilitation/secondary prevention programs
      (CR/SP) have consistently resulted in minimal weight loss, due in part to the low
      exercise-related EE. The purpose of this study was to measure the EE among
      patients participating in a routine exercise session of Phase III maintenance
      CR/SP, where a recreational activity was introduced. Twelve overweight/obese male
      patients with coronary artery disease (aged 62.6 +/- 8.5 years) had their total
      EE measured during a combined aerobic (circuit workout (ACW) and recreational
      activity) and resistance training (RT) session using a portable gas analyzer.
      Subjects were instructed to exercise at 60%-70% of heart rate reserve. Activity
      EE was calculated from total EE and resting EE. The duration of the session was
      75.3 +/- 1.5 min, of which 59.7 +/- 8.8 min were above moderate intensity (3-6
      METs). Activity EE was 309 +/- 76 kcal, concurring to a total EE of 457 +/- 80
      kcal (3.9 +/- 0.8 METs-h). ACW, recreational activity, and RT fulfilled 34.4% +/-
      6.4%, 25.0% +/- 5.3%, and 14.2% +/- 2.7% of the activity EE, respectively.
      Absolute intensities (METs) were significantly different between the RT (3.9 +/-
      1.0) and the ACW (6.9 +/- 1.8) and recreational activity (5.9 +/- 0.8). In
      conclusion, a combined aerobic and resistance training following standard
      exercise prescription practices, coupled with a recreational activity, is an
      effective tool to promote exercise above moderate intensity in male coronary
      artery disease patients. Clinicians can adopt concepts from recreational activity
      to develop CR/SP sessions.

PMID- 29073367
TI  - Principles of Systems Biology, No. 22.
AB  - This month: rules for valid synbio (Densmore), glycoproteomics (Penninger),
      selectivity by stability (Lemmon), cells in space and time (Rajewsky/Zinzen,
      Simons/Dirks, Chevrier, Aerts), what makes cells tick (Itzkovitz, Meunier,
      Pourquie, Vazquez-Garcia, Subramaniam, Driessen).

PMID- 29073366
TI  - Catheter-directed Thrombolysis for Intermediate-Risk Pulmonary Embolism.
AB  - Intermediate-risk pulmonary embolism is common and carries a risk of progression
      to hemodynamic collapse and death. Catheter-directed thrombolysis is an
      increasingly used treatment option, based largely on the assumptions that it is
      more efficacious than anticoagulation alone and safer than systemic thrombolysis.
      In this review, we critically analyze the published data regarding catheter
      directed thrombolysis for the treatment of intermediate-risk pulmonary embolism.
      Catheter-directed thrombolysis reduces right heart strain and lowers pulmonary
      artery pressures more quickly than anticoagulation alone. The mortality for
      patients with intermediate-risk pulmonary embolism treated with catheter-directed
      thrombolysis is low, between 0% and 4%. However, similarly low mortality is seen
      with anticoagulation alone. Catheter-directed thrombolysis appears to be safer
      than systemic thrombolysis, and procedural complications are uncommon. Bleeding
      risk appears to be slightly higher than with anticoagulation alone. Randomized,
      controlled trials are needed to compare the efficacy and safety of catheter
      directed thrombolysis versus anticoagulation for intermediate-risk pulmonary
      embolism. There is no evidence that catheter-directed thrombolysis decreases the
      incidence of chronic thromboembolic pulmonary hypertension. There is no evidence
      from clinical studies that ultrasound-assisted thrombolysis is more effective or
      safer than standard catheter-directed thrombolysis.

PMID- 29073364
TI  - Genetic, Immunologic, and Environmental Basis of Sarcoidosis.
AB  - Sarcoidosis is a multisystem disease with tremendous heterogeneity in disease
      manifestations, severity, and clinical course that varies among different ethnic
      and racial groups. To better understand this disease and to improve the outcomes
      of patients, a National Heart, Lung, and Blood Institute workshop was convened to
      assess the current state of knowledge, gaps, and research needs across the
      clinical, genetic, environmental, and immunologic arenas. We also explored to
      what extent the interplay of the genetic, environmental, and immunologic factors
      could explain the different phenotypes and outcomes of patients with sarcoidosis,
      including the chronic phenotypes that have the greatest healthcare burden. The
      potential use of current genetic, epigenetic, and immunologic tools along with
      study approaches that integrate environmental exposures and precise clinical
      phenotyping were also explored. Finally, we made expert panel-based consensus
      recommendations for research approaches and priorities to improve our
      understanding of the effect of these factors on the health outcomes in
      sarcoidosis.

PMID- 29073368
TI  - Defining Native Enhancer Function.
AB  - CRISPR inhibition is used to ablate the activity of regulatory elements alone and
      in combination, functionally linking regulatory elements to genes and revealing
      the logic of how these elements collaborate in their native genomic context.

PMID- 29073369
TI  - Isolation versus Enrichment: dCLIP Enables Stringent Profiling of RNA-Binding
      Sites.
AB  - Denaturing crosslinking and immunoprecipitation (dCLIP) enables stringent
      purification of ribonucleoprotein complexes to identify direct RNA targets of
      individual protein complex members.

PMID- 29073370
TI  - All for One, and One for All.
AB  - Hemizygous deletion of a gene in tumor cells frequently causes reduced expression
      of its encoded mRNA and protein, as well as reduced protein-but not mRNA
      expression of other members in the same protein complex.

PMID- 29073371
TI  - Computing at the Front-End by Receptor Networks.
AB  - Cells use receptors at their surface not just to transduce signals but also to
      perform computations before relaying them downstream.

PMID- 29073374
TI  - School start time changes and sleep patterns in elementary school students.
AB  - OBJECTIVES: Research finds significant sleep deprivation among adolescents with
      early school start times. This study surveyed sleep patterns in elementary school
      students before and after a district-wide change to earlier start times. DESIGN:
      Students in grades 3-5 completed a self-administered sleep survey in the spring
      of 2009 (third grade, n = 216; fourth grade, n = 214; fifth grade, n = 259;
      total, n = 689) and again in 2010 (third grade, n = 168; fourth grade, n = 194;
      fifth grade, n = 263; total, n = 625), after the school start time switched from
      8:20 am to 7:45 am in the Fall of 2009. Students entering grade 3 experienced a
      larger shift from 9:10 am to 7:45 am, due to moving from the kindergarten-second
      grade building to the third-to-fifth-grade building. Descriptive statistics
      quantified responses by grade. RESULTS: Prechange, wake time across all grades
      was similar; postchange, fourth and fifth graders woke on average 30-40 minutes
      earlier than children in those grades the year before, and third graders woke on
      average 8 minutes later. Compared to prechange, third graders reported longer
      average total sleep times (24 minutes); fourth and fifth graders reported average
      sleep times 4 and 9 minutes shorter, respectively, than students in those grades
      the previous year. The percentage of students in each grade reporting later
      weekend wake and bed times decreased postchange. Reports of sleepiness somewhat
      increased for fifth graders postchange. CONCLUSIONS: School start time change did
      not decrease total amount of sleep. This is the first study of its kind to report
      on the effects of a start time change in elementary school students.

PMID- 29073373
TI  - Denaturing CLIP, dCLIP, Pipeline Identifies Discrete RNA Footprints on Chromatin
      Associated Proteins and Reveals that CBX7 Targets 3' UTRs to Regulate mRNA
      Expression.
AB  - Interaction networks between chromatin complexes and long noncoding RNAs have
      become a recurrent theme in epigenetic regulation. However, technical limitations
      have precluded identification of RNA binding motifs for chromatin-associated
      proteins. Here, we add a denaturation step to UV-crosslink RNA
      immunoprecipitation (dCLIP) and apply dCLIP to mouse and human chromobox homolog
      7 (CBX7), an RNA binding subunit of Polycomb repressive complex 1 (PRC1). In both
      species, CBX7 predominantly binds 3' UTRs of messenger RNAs. CBX7 binds with a
      median RNA "footprint" of 171-183 nucleotides, the small size of which
      facilitates motif identification by bioinformatics. We find four families of
      consensus RNA motifs in mouse, and independent analysis of human CBX7 dCLIP data
      identifies similar motifs. Their mutation abolishes CBX7 binding in vitro.
      Pharmacological intervention with antisense oligonucleotides paradoxically
      increases CBX7 binding and enhances gene expression. These data support the
      utility of dCLIP and reveal an unexpected functional interaction between CBX7 and
      the 3' UTRs of mRNA.

PMID- 29073372
TI  - Mammalian Transcription Factor Networks: Recent Advances in Interrogating
      Biological Complexity.
AB  - Transcription factor (TF) networks are a key determinant of cell fate decisions
      in mammalian development and adult tissue homeostasis and are frequently
      corrupted in disease. However, our inability to experimentally resolve and
      interrogate the complexity of mammalian TF networks has hampered the progress in
      this field. Recent technological advances, in particular large-scale genome-wide
      approaches, single-cell methodologies, live-cell imaging, and genome editing, are
      emerging as important technologies in TF network biology. Several recent studies
      even suggest a need to re-evaluate established models of mammalian TF networks.
      Here, we provide a brief overview of current and emerging methods to define
      mammalian TF networks. We also discuss how these emerging technologies facilitate
      new ways to interrogate complex TF networks, consider the current open questions
      in the field, and comment on potential future directions and biomedical
      applications.

PMID- 29073375
TI  - Delayed sleep phase disorder risk is associated with absenteeism and impaired
      functioning.
AB  - STUDY OBJECTIVES: The absence of a screening questionnaire for delayed sleep
      phase disorder (DSPD) remains a barrier to its detection and subsequent clinical
      evaluation. We developed a questionnaire to screen for DSPD risk and assessed its
      impact on self-reported absenteeism and functioning in work/school, social, and
      family life. DESIGN: Cross-sectional, with 13,844 individuals responding to a
      survey through an Internet survey provider, from which 1315 completed surveys
      were obtained from eligible participants. PARTICIPANTS: A total of 1315
      individuals who self-identified as evening type (n=979) or as non-evening type
      (n=356). MEASUREMENTS AND RESULTS: A total of 295 participants were at high risk
      for DSPD, which is 5.1% of the total eligible survey respondents and 22.4% of our
      final sample with completed surveys. Compared to those who were not at high risk
      for DSPD, those who were at high risk were more likely to report frequent
      absenteeism, frequent loss of productivity, disruption to work or school
      activities, disruption to social life or leisure activities, and disruption to
      family life or home responsibilities. Difficulty with daytime sleepiness was more
      common in those at high risk for DSPD than those who were not. Increased sleep
      deficit on nights before school or work was also associated with more frequent
      difficulties with daytime sleepiness; 15.4% of those with no sleep deficit
      reported always or usually having difficulties with daytime sleepiness compared
      to 55.7% of those with a sleep deficit of 3hours or more. CONCLUSIONS: DSPD risk
      is associated with increased absenteeism and impaired functioning in work/school,
      social, and family life.

PMID- 29073376
TI  - Sleep apnea severity and depressive symptoms in a population-based study.
AB  - OBJECTIVES: Sleep apnea and depression often co-occur in clinical studies, but
      population-based studies demonstrated mixed results. We determined the
      association of sleep apnea severity and depressive symptoms in a population-based
      sample. DESIGN: Cross-sectional cohort study. SETTING: Population-based.
      PARTICIPANTS: Four hundred ninety-one middle-aged and elderly persons of the
      Rotterdam Study (mean age 61.9 years; standard deviation, 5.4). MEASUREMENTS:
      Polysomnography recordings were collected to calculate the apnea hypopnea index
      (AHI). Depressive symptoms were assessed with the Center for Epidemiologic
      Studies Depression Scale. RESULTS: In the total sample, no associations for the
      severity of sleep apnea with depressive symptoms were found (multivariate
      adjusted: B = 0.032; 95% confidence interval [CI], -0.057 to 0.122). Only in men
      we found some evidence for a curvilinear association of the severity of sleep
      apnea with depressive symptoms (multivariable adjusted: B = -0.126; 95% CI, 
      0.224 to -0.028); men with an AHI between 5 and 15 (multivariable adjusted: B =
      0.378; 95% CI, 0.037-0.718) or between 15 and 30 (multivariable adjusted: B =
      0.502; 95% CI, 0.152-0.852) had significantly more depressive symptoms than those
      with an AHI equal to or greater than 30. CONCLUSIONS: In this population-based
      sample, the severity of sleep apnea is not consistently related to depressive
      symptoms, although there was some evidence for an association of AHI with
      depressive symptoms in men.

PMID- 29073377
TI  - Agreement between simple questions about sleep duration and sleep diaries in a
      large online survey.
AB  - INTRODUCTION: Self-reported habitual sleep duration has been used widely in
      epidemiologic research, yet this measure remains to be validated. We evaluated
      whether simple sleep duration questions concord with sleep diaries in an online
      sample. METHODS: Australian adults aged 18+ years completed an internet survey
      examining measures of sleep, sociodemographic risk factors, and a 7-day sleep
      diary. We examined single-question (how many hours of sleep would you normally
      get?) and 2-question assessments (difference between sleep and wake times) to a 7
      day sleep diary estimation of sleep duration. Using Bland-Altman plots and
      associated statistics, we tested systematic differences, precision, and
      systematic bias. We also evaluated whether the differences were consistent along
      the entire range of the measurement and whether they were associated with any
      sociodemographic risk factors (Spearman rho). RESULTS: Data were analyzed from
      1662 participants (67.3% female). Bland-Altman plots displayed visual
      discrepancies between both 1-question and 2-question reports of sleep duration
      compared with sleep diaries. Both the single- (-17 minutes) and double-question
      (8 minutes) sleep duration estimates differed significantly (both P < .001).
      These simple estimates only agreed to within +/-2.5-3 hours compared with diary
      estimates. The measure was also weakly systematically biased (rho = +0.204 and
      +0.309, P < .001) through the measurement range. There were significant
      differences and associations between differences in sleep duration estimation and
      determinants of health. CONCLUSIONS: Simple questions estimating habitual sleep
      duration are imprecise and systematically biased in a large online survey. The
      amount of difference is correlated with well-known sociodemographic risk factors.

PMID- 29073378
TI  - Commentary on Agreement between simple questions about sleep duration and sleep
      diaries in a large online survey.

PMID- 29073379
TI  - Sleep Health makes an impact!

PMID- 29073380
TI  - Sleep's embrace.

PMID- 29073381
TI  - Sleep and pain: summary of the 2015 Sleep in America Poll.

PMID- 29073382
TI  - Healthy sleep in young children: missed opportunity in early childhood programs
      and policies?

PMID- 29073383
TI  - A natural view of artificial light.

PMID- 29073384
TI  - Disentangling racial/ethnic and socioeconomic differences in self-reported sleep
      measures: the Boston Area Community Health Survey.
AB  - BACKGROUND: Racial/ethnic differences in sleep are widely reported. However, the
      extent to which socioeconomic factors account for crude variation in sleep
      parameters by racial/ethnic groups is not clearly understood. METHODS: We studied
      4144 individuals in the Boston Area Community Health Survey (2006-2010), a
      racially/ethnically balanced population-based cohort of black, Hispanic, and
      white men and women. Self-reported sleep measures were sleep duration, sleep
      latency, restless sleep, risk for sleep apnea, and sleep medication use. We
      assessed changes in the age- and sex-adjusted association between race/ethnicity
      and sleep measures after additional adjustment for individual socioeconomic
      factors (income, education, and employment) and lifestyle and behavioral factors.
      RESULTS: Self-identified non-Hispanic black race/ethnicity was significantly
      associated with higher odds of short sleep duration (fully adjusted odds ratio
      [OR], 1.93; 95% confidence interval [CI], 1.41-2.64), longer sleep latency (fully
      adjusted, 20.9% longer; 95% CI, 4.1-41.9), and lower odds of pharmaceutical sleep
      aid use (fully adjusted OR: 0.47, 95% CI: 0.34, 0.65) than white race/ethnicity.
      Education level accounted for the most substantial reduction in estimates of the
      age- and sex-adjusted association between black race/ethnicity and short sleep
      duration and sleep latency. Having less than a 4-year college education was
      associated with approximately 55% lower sleep latency than having postgraduate
      education. No significant associations were observed comparing Hispanic to white
      participants. CONCLUSIONS: Significant variation was observed between black and
      white race/ethnicity in short sleep duration, sleep latency, and sleep aid use.
      Although considerable variation in sleep by race/ethnicity was explained by
      education level, additional variation in self-reported sleep by race/ethnicity
      may be due to other unmeasured socioeconomic, lifestyle, or behavioral factors.

PMID- 29073385
TI  - The impact of home safety on sleep in a Latin American country.
AB  - OBJECTIVES: We sought to assess the impact of feelings of safety in one's
      neighborhood and home on sleep quality and sleep duration. DESIGN: The design is
      a cross-sectional survey using face-to-face interviews, as part of the Argentine
      Social Debt Observatory assessment. SETTING: The setting is a nationwide data
      from Argentina. PARTICIPANTS: There are 5636 participants aged 18 years and
      older. INTERVENTION (IF ANY): N/A. MEASUREMENTS: The relationships between both
      subjective sleep quality and self-reported sleep duration, categorized as short
      (<7 hours), normal (7-8 hours), and long (>8 hours) with safety in one's
      neighborhood and one's home, were analyzed. Age, sex, obesity, neighborhood
      socioeconomic status, and education were included as covariates. RESULTS: Feeling
      unsafe in one's home was strongly associated with poorer sleep quality and with
      short sleep duration. Feeling unsafe in one's neighborhood was initially
      associated with reduced sleep quality but was no longer significant after
      controlling for home safety. In contrast, we found no correlation between safety
      measures and long sleep. In analyses stratified by sex, feeling unsafe in one's
      home was associated with poor sleep quality in women but not in men. CONCLUSIONS:
      Our findings suggest that safety in the home has an important effect on both
      sleep quality and duration, particularly among women. In contrast, after
      accounting for safety in the home, neighborhood safety does not impact sleep.
      Further research is warranted to identify mechanisms underlying the sex
      differences in susceptibility to poor sleep quality and shorter sleep duration,
      as well as to assess whether interventions addressing safety in the home can be
      used to improve sleep and overall health.

PMID- 29073386
TI  - Sleep: a refuge from danger.

PMID- 29073387
TI  - Translating Sleep Science Into Policy.

PMID- 29073388
TI  - Relationships between body mass index and sleep quality and duration in adults 70
      years and older.
AB  - OBJECTIVE: Associations between sleep and body mass index (BMI) are age
      dependent. In older adults, BMI norms representing normal and overweight combine
      into a single normal-weight category. We aimed to assess the nonlinear
      associations between age-appropriate BMI categories and sleep duration (SD) and
      sleep efficiency (SE) in older men and women, controlling for health and
      functional status. METHODS: Secondary data analysis of the Hospitalization
      Process Effects on Functional Outcomes and Recovery included 719 community
      dwelling adults age 70+ years hospitalized because of nondisabling diagnoses.
      Self-report intake data regarding their condition prior to circumstances that led
      to hospitalization were used to obtain BMI categories (underweight: BMId23,
      normal weight: 23<BMI<30, and obese: BMI>=30), SD, SE, health, and functional
      status. Analysis of covariance was used for modeling SD and SE separately,
      additively entering (1) BMI, (2) sex and BMI*sex, and (3) health and functional
      confounders. RESULTS: For SD and SE, significant BMI group differences in the
      first model (P<.001) remained significant in the second (P<.001) and third
      (P<.01) models. High BMI was associated with shorter SD and lower SE compared
      with normal- and low-BMI groups. Controlling for sex, an inverted J-shaped
      relationship appeared in women, whereby low- and, more prominently, high-BMI
      categories were associated with shorter SD and lower SE compared with normal BMI.
      Although associations remained consistent in the fully adjusted models, effect
      sizes were small. CONCLUSIONS: Findings provide insights into possible mechanisms
      underlying BMI, sleep, and health and may contribute to informed clinical
      recommendations, particularly for older women.

PMID- 29073389
TI  - Impact of extended duty hours on medical trainees.
AB  - Many studies on resident physicians have demonstrated that extended work hours
      are associated with a negative impact on well-being, education, and patient care.
      However, the relationship between the work schedule and the degree of impairment
      remains unclear. In recent years, because of concerns for patient safety,
      national minimum standards for duty hours have been instituted (2003) and revised
      (2011). These changes were based on studies of the effects of sleep deprivation
      on human performance and specifically on the effect of extended shifts on
      resident performance. These requirements necessitated significant restructuring
      of resident schedules. Concerns were raised that these changes have impaired
      continuity of care, resident education and supervision, and patient safety. We
      review the studies on the effect of extended work hours on resident well-being,
      education, and patient care as well as those assessing the effect of work hour
      restrictions. Although many studies support the adverse effects of extended
      shifts, there are some conflicting results due to factors such as heterogeneity
      of protocols, schedules, subjects, and environments. Assessment of the effect of
      work hour restrictions has been even more difficult. Recent data demonstrating
      that work hour limitations have not been associated with improvement in patient
      outcomes or resident education and well-being have been interpreted as support
      for lifting restrictions in some specialties. However, these studies have
      significant limitations and should be interpreted with caution. Until future
      research clarifies duty hours that optimize patient outcomes, resident education,
      and well-being, it is recommended that current regulations be followed.

PMID- 29073391
TI  - Parental social capital and children's sleep disturbances.
AB  - OBJECTIVES: Sleep plays a critical role in the health and well-being of children.
      Individual and household factors, including parent's social connections, may
      impact children's sleep. Our study assessed the association between children's
      sleep disturbances and parent's social capital in a sample of Canadian
      households. DESIGN: Cross-sectional, observational study. SETTINGS AND
      PARTICIPANTS: Data came from 339 children and their parents who completed a
      telephone and follow-up survey in 2013 as part of the Canada Brain-to-Society
      study. Participants were parents (73.1% female) with children aged 6 to 12years
      residing in Montreal, Canada. MEASUREMENTS: Parental social capital was assessed
      using a position generator, and children's sleep disturbances were measured with
      the Children's Sleep Habits Questionnaire. Other household demographic and
      socioeconomic characteristics were measured, including parental and child age and
      sex, foreign-born status, and income. Linear regression was used to examine the
      association between parental social capital and children's sleep disturbances
      while controlling for possible confounders. RESULTS: Parental social capital was
      negatively associated with children's sleep disturbances (beta=-0.02, SE=0.01,
      P<.05), when controlling for demographic factors (sex of parent, household
      income, foreign-born status, parent's age, sex and age of child, suggesting that
      children of parents with higher social capital had fewer sleep disturbances.
      CONCLUSIONS: Parents with higher social capital tended to have children with few
      total sleep disturbances than did parents with lower social capital. Parental
      social capital may be a potentially modifiable aspect of the home environment
      that has implications for children's health.

PMID- 29073390
TI  - Poor sleep health and its association with mental health, substance use, and
      condomless anal intercourse among gay, bisexual, and other men who have sex with
      men.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prevalence of poor
      sleep health (ie, poor sleep quality and short sleep duration) in a sample of men
      who have sex with men (MSM). In addition, this study examined whether poor sleep
      health was associated with depressive symptoms, substance use, and sexual risk
      behaviors in this sample. DESIGN: Cross-sectional survey. PARTICIPANTS: Broadcast
      advertisements were placed on a popular smartphone application for MSM in January
      2016 to recruit users in the London metropolitan area (n=202) to complete a Web
      based survey, which included validated measures of sleep quality and duration.
      MEASUREMENTS: Poor sleep quality was defined based on self-report as very or
      fairly bad. Short sleep duration was defined as less than 7 hours each night.
      Regression models were used to assess associations between sleep variables and
      self-reported depressive symptoms, substance use, and sexual risk behaviors.
      RESULTS: About one-third (34.6%) of the respondents reported poor sleep quality
      and almost half (43.6%) reported sleeping less than 7 hours every night. Several
      poor sleep health variables were independently associated with depressive
      symptoms, substance use (eg, use of alcohol or marijuana), and condomless anal
      intercourse. For example, typical nightly sleep duration of less than 7 hours was
      associated with condomless receptive anal intercourse with a higher number of
      sexual partners (incidence rate ratio, 2.65; 95% confidence interval: 1.63-4.30;
      P<.001). CONCLUSION: Sleep health promotion interventions should be developed for
      MSM, which may promote positive mental health as well as reduce substance use and
      sexual risk behaviors in this population.

PMID- 29073392
TI  - Screen and nonscreen sedentary behavior and sleep in adolescents.
AB  - OBJECTIVE: This study examined the associations between screen (computer,
      videogame, TV) and nonscreen (talking on the phone, doing homework, reading)
      sedentary time, and sleep in adolescents. PARTICIPANTS: Data were drawn from
      AdoQuest, a prospective investigation of 1843 grade 5 students aged 10-12 years
      at inception in the greater Montreal (Canada) area. METHODS: Data for this cross
      sectional analysis on screen and nonscreen sedentary time, sleep duration, and
      daytime sleepiness were collected in 2008-2009 from 1233 participants (67% of
      1843) aged 14-16 years. RESULTS: Computer and videogame use >2 hours per day was
      associated with 17 and 11 fewer minutes of sleep per night, respectively.
      Computer use and talking on the phone were both associated with being a short
      sleeper (<8 hour per night) (odds ratio =2.2 [1.4-3.4] and 3.0 [1.5-6.2],
      respectively), whereas TV time was protective (odds ratio=0.5 [0.3-0.8]).
      Participants who reported >2 hours of computer use or talking on the phone per
      day had higher daytime sleepiness scores (11.9 and 13.9, respectively) than
      participants who reported d2 hours per day (9.7 and 10.3, respectively).
      CONCLUSIONS: Computer use and time spent talking on the phone are associated with
      short sleep and more daytime sleepiness in adolescents. Videogame time is also
      associated with less sleep. Clinicians, parents, and adolescents should be made
      aware that sedentary behavior and especially screen-related sedentary behavior
      may affect sleep duration negatively and is possibly associated with daytime
      sleepiness.

PMID- 29073393
TI  - What is segmented sleep? Actigraphy field validation for daytime sleep and
      nighttime wake.
AB  - OBJECTIVE: To compare different scoring parameter settings in actigraphy software
      for inferring sleep and wake bouts for validating analytical techniques outside
      of laboratory environments. DESIGN: To identify parameter settings that best
      identify napping during periods of wakefulness, we analyzed 137 days on which
      participants reported daytime napping, as compared with a random subset of 30
      days when no naps were reported. To identify settings that identify periods of
      wakefulness during sleep, we used data from a subsample of women who reported
      discrete wake bouts while nursing at night. SETTING: Equatorial Tanzania in
      January to February 2016. PARTICIPANTS: The Hadza-a non-industrial foraging
      population. MEASUREMENTS: Thirty-three subjects participated in the study for 393
      observation days. Using the Bland-Altman technique to determine concordance, we
      analyzed reported events of daytime napping and nighttime wake bouts. RESULTS:
      Only 1 parameter setting could reliably detect reported naps (15-minute nap
      length, <=50 counts). Moreover, of the 6 tested parameter settings to detect wake
      bouts, the setting where the sleep-wake algorithm was parameterized to detect 20
      consecutive minutes throughout the designated sleep period did not overestimate
      or underestimate wake bouts, had the lowest mean difference, and did not
      significantly differ from reported wake-bout events. CONCLUSION: We propose
      operational definitions for multiple dimensions of segmented sleep and conclude
      that actigraphy is an effective method for detecting segmented sleep in future
      cross-site comparative research. The implications of such work are far reaching,
      as sleep research in preindustrial and developing societies is documenting
      natural sleep-wake patterns in previously inaccessible environments.

PMID- 29073394
TI  - Sleep Health's first year.

PMID- 29073396
TI  - Arthur Spielman: in memoriam (1947-2015).

PMID- 29073395
TI  - Entering a dream.

PMID- 29073397
TI  - Siesta by decree or sound policy to promote sleep health? Lessons from a
      municipal proclamation in a rural Spanish town.

PMID- 29073398
TI  - National Sleep Foundation's updated sleep duration recommendations: final report.
AB  - OBJECTIVE: To make scientifically sound and practical recommendations for daily
      sleep duration across the life span. METHODS: The National Sleep Foundation
      convened a multidisciplinary expert panel (Panel) with broad representation from
      leading stakeholder organizations. The Panel evaluated the latest scientific
      evidence and participated in a formal consensus and voting process. Then, the
      RAND/UCLA Appropriateness Method was used to formulate sleep duration
      recommendations. RESULTS: The Panel made sleep duration recommendations for 9 age
      groups. Sleep duration ranges, expressed as hours of sleep per day, were
      designated as recommended, may be appropriate, or not recommended. Recommended
      sleep durations are as follows: 14-17 hours for newborns, 12-15 hours for
      infants, 11-14 hours for toddlers, 10-13 hours for preschoolers, 9-11 hours for
      school-aged children, and 8-10 hours for teenagers. Seven to 9 hours is
      recommended for young adults and adults, and 7-8 hours of sleep is recommended
      for older adults. The self-designated basis for duration selection and critical
      discussions are also provided. CONCLUSIONS: Consensus for sleep duration
      recommendations was reached for specific age groupings. Consensus using a
      multidisciplinary expert Panel lends robust credibility to the results. Finally,
      limitations and caveats of these recommendations are discussed.

PMID- 29073400
TI  - Sleep restriction and delayed sleep associate with psychological health and
      biomarkers of stress and inflammation in women.
AB  - STUDY OBJECTIVES: Despite strong associations between sleep duration and health,
      there is no clear understanding of how volitional chronic sleep restriction (CSR)
      alters the physiological processes that lead to poor health in women. We focused
      on biochemical and psychological factors that previous research suggests are
      essential to uncovering the role of sleep in health. DESIGN: Cross-sectional
      study. SETTING: University-based. PARTICIPANTS: Sixty female participants (mean
      age, 19.3; SD, 2.1 years). MEASUREMENTS: We analyzed the association between self
      reported volitional CSR and time to go to sleep on a series of sleep and
      psychological health measures as well as biomarkers of immune
      functioning/inflammation (interleukin [IL]-1beta), stress (cortisol), and sleep
      regulation (melatonin). RESULTS: Across multiple measures, poor sleep was
      associated with decreased psychological health and a reduced perception of self
      reported physical health. Volitional CSR was related to increased cortisol and
      increased IL-1beta levels. We separately looked at individuals who experienced
      CSR with and without delayed sleep time and found that IL-1beta levels were
      significantly elevated in CSR alone and in CSR combined with a late sleep time.
      Cortisol, however, was only elevated in those women who experienced CSR combined
      with a late sleep time. We did not observe any changes in melatonin across
      groups, and melatonin levels were not related to any sleep measures. CONCLUSIONS:
      New to our study is the demonstration of how an increase in a proinflammatory
      process and an increase in hypothalamic-pituitary-adrenal axis activity both
      relate to volitional CSR, with and without a delayed sleep time. We further show
      how these mechanisms relate back to psychological and self-reported health in
      young adult women.

PMID- 29073399
TI  - Obstructive sleep apnea and stroke: links to health disparities.
AB  - Obstructive sleep apnea (OSA) is a novel cardiovascular and cerebrovascular risk
      factor that presents unique opportunities to understand and reduce seemingly
      intractable stroke disparity among non-Hispanic blacks and Hispanic/Latinos.
      Individuals from these 2 groups have up to a 2-fold risk of stroke and greater
      burden of OSA. Obstructive sleep apnea directly and indirectly increases risk of
      stroke through a variety of autonomic, chemical, and inflammatory mechanisms and
      vascular risk factors such as hypertension, obesity, and diabetes mellitus.
      Untreated OSA exacerbates poststroke prognosis, as it may also influence
      rehabilitation efforts and functional outcomes such as cognitive function after a
      stroke. Conversely, treatment of OSA may reduce the risk of stroke and may yield
      better poststroke prognosis. Unfortunately, in racial/ethnic minority groups,
      there are limited awareness, knowledge, and screening opportunities for OSA.
      Increasing awareness and improving screening strategies for OSA in minorities may
      alleviate stroke risk burden and improve stroke outcomes in these populations.
      This review article is intended to highlight the epidemiology, clinical
      characteristics, pathophysiology, diagnosis, and treatment of OSA in relation to
      stroke risk, with an emphasis on race-ethnic disparities.

PMID- 29073401
TI  - Effect of different mattress designs on promoting sleep quality, pain reduction,
      and spinal alignment in adults with or without back pain; systematic review of
      controlled trials.
AB  - A significant number of US citizens lack appropriate sleep for several reasons.
      Back pain has been identified as possible cause for inappropriate sleep in
      adults. Previously, the quality of mattresses and bedding systems has been
      correlated to the pain perceived by individuals. However, there is controversy in
      the literature regarding the type and characteristics of a mattress that best
      serve the purpose of decreasing spinal pain, and improving spinal alignment and
      quality of sleep. This study gathered the best available evidence in the
      literature related to this matter through conducting a systematic review of
      controlled trials that were published since the year of 2000. In those trials,
      mattresses were subjectively identified as soft, medium firm, firm, or custom
      inflated. Articles examining the effect of temperature alterations of mattresses
      on promoting sleep quality and reducing pain were included as well. Twenty-four
      articles qualified for inclusion into this systematic review. The methodological
      quality of the reviewed clinical trials was deemed moderate to high according to
      the PEDro scale. Results of this systematic review show that a mattress that is
      subjectively identified as a medium-firm mattress and is custom inflated (self
      adjusted) is optimal for promoting sleep comfort, quality, and spinal alignment.
      Evidence is not sufficient yet regarding the appropriate temperature of the
      optimum mattress; however, warm temperature has been recommended by authors.

PMID- 29073402
TI  - Sleep deprivation and adverse health effects in United States Coast Guard
      responders to Hurricanes Katrina and Rita.
AB  - OBJECTIVE: Disaster responders are increasingly called upon to assist in various
      natural and manmade disasters. A critical safety concern for this population is
      sleep deprivation; however, there are limited published data regarding sleep
      deprivation and disaster responder safety. DESIGN: We expanded upon a cross
      sectional study of 2695 United States Coast Guard personnel who responded to
      Hurricanes Katrina and Rita. Data were collected via survey on self-reported
      timing and location of deployment, missions performed, health effects, medical
      treatment sought, average nightly sleep, and other lifestyle variables. We
      created a 4-level sleep deprivation metric based on both average nightly reported
      sleep (d5hours; >5hours) and length of deployment (d2weeks; >2weeks) to examine
      the association between sustained sleep deprivation and illnesses, injuries, and
      symptoms using logistic regression to calculate odds ratios (ORs) and 95%
      confidence intervals. RESULTS: The strongest, statistically significant positive
      ORs for the highest sleep deprivation category compared with the least sleep
      deprived category were for mental health and neurologic effects, specifically
      depression (OR=6.76), difficulty concentrating (OR=8.33), and confusion
      (OR=11.34), and for dehydration (OR=9.0). Injuries most strongly associated with
      sleep deprivation were twists, sprains, and strains (OR=6.20). Most health
      outcomes evaluated had monotonically increasing ORs with increasing sleep
      deprivation, and P tests for trend were statistically significant. CONCLUSION:
      Agencies deploying disaster responders should understand the risks incurred to
      their personnel by sustained sleep deprivation. Improved planning of response
      efforts to disasters can reduce the potential for sleep deprivation and lead to
      decreased morbidity in disaster responders.

PMID- 29073403
TI  - Practical considerations in using accelerometers to assess physical activity,
      sedentary behavior, and sleep.
AB  - Increasingly, behavioral and epidemiological research uses activity-based
      measurements (accelerometry) to provide objective estimates of physical activity,
      sedentary behavior, and sleep in a variety of study designs. As interest in
      concurrently assessing these domains grows, there are key methodological
      considerations that influence the choice of monitoring instrument, analysis
      algorithm, and protocol for measuring these behaviors. The purpose of this review
      is to summarize evidence-guided information for 7 areas that are of importance in
      the design and interpretation of studies using actigraphy: (1) choice of cut
      points; (2) impact of epoch length; (3) accelerometer placement; (4) duration of
      monitoring; (5) approaches for distinguishing sleep, nonwear times, and sedentary
      behavior; (6) role for a sleep and activity diary; and (7) epidemiological
      applications. Recommendations for future research are outlined and are intended
      to enhance the appropriate use of accelerometry for assessing physical activity,
      sedentary behavior, and sleep behaviors in research studies.

PMID- 29073404
TI  - Impact of childhood abuse on adult sleep quality among low-income women after
      Hurricane Ike.
AB  - OBJECTIVE: The objective was to investigate the association between childhood
      abuse and poor sleep quality in the month following adulthood exposure to a
      natural disaster. DESIGN: Cross-sectional. SETTING: Six University of Texas
      Medical Branch family planning clinics located in Southeast Texas. PARTICIPANTS:
      A subgroup of 375 low-income women aged 18 to 31 years who experienced Hurricane
      Ike while participating in the Stress and Health Longitudinal Study (2006-2012).
      MEASUREMENTS: Risk profiles considering types and frequency of childhood abuse
      were identified in latent class analysis performed on the Childhood Trauma
      Questionnaire, which was measured upon entry to the study. Associations between
      abuse classes with a global indicator and 7 individual components of sleep
      quality measured after Hurricane Ike were estimated in adjusted logistic
      regression models. RESULTS: Prevalence of poor sleep quality in the month
      following Hurricane Ike was 39.7%. Of the 5 classes of childhood abuse
      identified, the most extreme abuse class--frequent combined emotional, physical,
      and sexual abuse--exhibited the strongest associations with poor sleep quality
      after the hurricane (odds ratio: 4.30; 95% confidence interval: 1.72-10.72).
      Occasional emotional abuse alone was also significantly associated with poor
      sleep quality after the hurricane (odds ratio: 2.70; 95% confidence interval:
      1.48-4.91). Several profiles of childhood abuse were also significantly
      associated with 6 of the 7 component indicators of sleep quality, including sleep
      duration, disturbances, onset latency, subjective quality, use of sleep
      medication, and daytime dysfunction. CONCLUSIONS: Low-income women with histories
      of frequent childhood abuse, or emotional abuse specifically, have increased risk
      of poor sleep quality following exposure to a hurricane in adulthood.

PMID- 29073405
TI  - Social conversation and its relationship to sleep behavior among college
      students.
AB  - Sleep health is compromised during the college years; college students have
      shortened sleep duration and often keep inconsistent sleep schedules. One strong
      predictor that has been identified in previous research on college student sleep
      is dysfunctional beliefs like worry and perceived lack of control. Less
      understood are the contributing factors to these dysfunctional beliefs. This
      paper draws on a social science perspective to examine how college students talk
      about sleep and how these conversations relate to beliefs and intentions to
      sleep. In a 2-step mixed-methods design, this study explores conversations among
      college students about sleep and how these conversations relate to sleep-related
      cognitions and behaviors (n=301). College students report frequently talking
      about sleep-damaging topics (staying up late, daytime sleepiness), and this
      discussion is associated with lower cognitive beliefs about behavioral control
      and lower intention to sleep. Regression results show a negative relationship
      between sleep behaviors and sleep-damaging conversations (beta=-0.41; P<.001).
      Perceived control over sleep patterns was strongly associated with sleep behavior
      (beta=0.46; P<.001), and evidence was found that this belief might partially
      mediate the relationship between sleep-damaging talk and behavior. Implications
      for sleep education and promotion efforts on college campuses are offered.

PMID- 29073406
TI  - Regulating danger on the highways: hours of service regulations.
AB  - OBJECTIVES: Current hours of service regulations governing commercial truck
      drivers in place in the United States, Canada, Australia, and the European Union
      are summarized and compared to facilitate the assessment of the effectiveness of
      such provisions in preventing fatigue and drowsiness among truck drivers.
      METHODS: Current hours of service provisions governing commercial truck drivers
      were derived from governmental sources. RESULTS: The commercial truck driver
      hours of service provisions in the United States, Canada, and the European Union
      permit drivers to work 14 hours and those of Australia permit drivers to work 12
      hours a day on a regular basis. The regulations do not state what a driver may do
      with time off. They are consistent with a driver being able to drive after 24
      hours without sleep. They do not take into account circadian rhythm by linking
      driving or rest to time of day. CONCLUSIONS: Current hours of service regulations
      governing commercial truck drivers leave gaps--permitting drivers to work long
      hours on a regular basis, permitting driving after no sleep for 24 hours, and
      failing to take into account the importance of circadian rhythm, endangering the
      public safety and the truck drivers themselves.

PMID- 29073407
TI  - Restricted use of electronic media, sleep, performance, and mood in high school
      athletes--a randomized trial.
AB  - OBJECTIVES: The study aims to evaluate whether 4 weeks with restricted use of
      electronic media after 22:00 affects sleep, athletic performance, cognitive
      performance, and mood in high school athletes. METHODS: Eighty-five athletes were
      randomized to either an intervention group (n = 44), who was instructed to not
      use any electronic media after 22:00, or a control condition (n = 41), where they
      could act as they preferred in terms of media use. Primary outcomes were sleep
      habits measured with a sleep diary. Secondary outcomes were (a) physical
      performance measured with a set of standardized tests (beep test, 20-m linear
      sprint, chin-up test, hanging sit-ups test, counter movement jump and sit-n-reach
      test); (b) cognitive performance (response time and response accuracy); and (c)
      positive and negative affect. Differences between groups were tested with mixed
      between-within subject analyses of variance. RESULTS AND CONCLUSIONS: Thirty-five
      and 40 of the athletes in the intervention and control group, respectively,
      completed the study. Results showed that restricted use of electronic media after
      22:00 did not improve sleep habits, athletic performance, cognitive performance,
      or mood in a group of high school top athletes with already good sleep habits.
      However, these findings give us knowledge about sleep habits and performance in
      this population that is of importance when designing future studies.

PMID- 29073408
TI  - An introduction and invitation to join our sleep health community.

PMID- 29073409
TI  - Is sleep a luxury that college students cannot afford?

PMID- 29073410
TI  - Noon: Rest from Work, after Jean-Francois Millet by Vincent van Gogh.

PMID- 29073411
TI  - Adolescent sleep disparities: sex and racial/ethnic differences.
AB  - OBJECTIVES: During adolescence, significant changes occur in sleep (eg, decreased
      sleep duration and increased sleep problems). To date, few studies have examined
      whether self-reported sleep duration differences exist between races/ethnicities
      in early adolescence (ages 11-14 years). METHODS: This study compared sexes and
      race/ethnicity groups on self-reported sleep duration in a large (n = 1543; 48.9%
      boys) racially/ethnically diverse (62.7% White, 23.7% Hispanic/Latino, 10.4%
      African American, and 3.2% Asian) sample of young adolescents (mean age, 12.31)
      drawn from local middle schools. RESULTS: A 2-way analysis of variance revealed
      that there was a trend for a significant sex effect (P = .067, partial chi2 =
      .002), with boys reporting more sleep than girls and significant race/ethnicity
      effects (P < .001, partial chi2 = .012), with Hispanic and African American
      students reporting shorter sleep duration than White and Asian students. The
      interaction between sex * race/ethnicity was significant (P = .014, partial chi2
      = .002), with post hoc tests revealing that Hispanic males demonstrated
      significantly shorter sleep duration than White and Asian males and African
      American females demonstrating significantly shorter sleep duration than White
      females. CONCLUSIONS: Given the literature showing short sleep duration is
      related to various negative health outcomes and all-cause mortality, more
      research is needed to determine the factors involved in these disparities.
      Adolescent sleep disparities: sex and racial/ethnic differences.

PMID- 29073413
TI  - Longitudinal relations between children's sleep and body mass index: the
      moderating role of socioeconomic risk.

PMID- 29073412
TI  - National Sleep Foundation's sleep time duration recommendations: methodology and
      results summary.
AB  - OBJECTIVE: The objective was to conduct a scientifically rigorous update to the
      National Sleep Foundation's sleep duration recommendations. METHODS: The National
      Sleep Foundation convened an 18-member multidisciplinary expert panel,
      representing 12 stakeholder organizations, to evaluate scientific literature
      concerning sleep duration recommendations. We determined expert recommendations
      for sufficient sleep durations across the lifespan using the RAND/UCLA
      Appropriateness Method. RESULTS: The panel agreed that, for healthy individuals
      with normal sleep, the appropriate sleep duration for newborns is between 14 and
      17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours,
      preschoolers between 10 and 13 hours, and school-aged children between 9 and 11
      hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for
      young adults and adults, and 7 to 8 hours of sleep for older adults. CONCLUSIONS:
      Sufficient sleep duration requirements vary across the lifespan and from person
      to person. The recommendations reported here represent guidelines for healthy
      individuals and those not suffering from a sleep disorder. Sleep durations
      outside the recommended range may be appropriate, but deviating far from the
      normal range is rare. Individuals who habitually sleep outside the normal range
      may be exhibiting signs or symptoms of serious health problems or, if done
      volitionally, may be compromising their health and well-being.

PMID- 29073414
TI  - Duration, timing and quality of sleep are each vital for health, performance and
      safety.

PMID- 29073415
TI  - Sleep maintenance difficulties in insomnia are associated with increased
      incidence of hypertension.
AB  - STUDY OBJECTIVES: We examined the relative contributions of sleep onset and sleep
      maintenance difficulties in insomnia as predictors of incidence and development
      of hypertension. DESIGN: This study is cross-sectional and longitudinal.
      PARTICIPANTS: There were 967 adults with Diagnostic and Statistical Manual of
      Mental Disorders, Fifth Edition-based current insomnia. MEASUREMENTS AND RESULTS:
      At baseline, participants were divided into 2 groups based on current diagnosis
      of hypertension. Prevalence of hypertension in this sample was 34.7%, which is
      higher than the prevalence in the general population previously documented at
      approximately 28%. Participants completed a follow-up assessment 1 year later
      that revealed a 5.4% incidence of hypertension. Analyses revealed that increases
      in sleep maintenance difficulties, not sleep initiation difficulties, between
      baseline and follow-up significantly predicted increased risk for incidence of
      hypertension. Analyses at baseline also revealed that sleep maintenance rather
      than sleep initiation difficulties marginally predicted increased severity of
      hypertension. Results suggest that risk for hypertension may be conferred through
      disruptions to blood pressure with nightly repeated or prolonged awakenings.
      CONCLUSIONS: This study provides novel information regarding the risk of
      hypertension in insomnia via sleep maintenance difficulties. Findings from this
      study provide preliminary evidence for examining nighttime fluctuations of blood
      pressure and concomitant physiological changes (ie, catecholamines, heart rate,
      and sympathetic activation) due to wake during sleep as a mechanism for
      subsequent hypertension.

PMID- 29073416
TI  - A workplace intervention improves sleep: results from the randomized controlled
      Work, Family, and Health Study.
AB  - STUDY OBJECTIVES: The Work, Family, and Health Network Study tested the
      hypothesis that a workplace intervention designed to increase family-supportive
      supervision and employee control over work time improves actigraphic measures of
      sleep quantity and quality. DESIGN: Cluster-randomized trial. SETTING: A global
      information technology firm. PARTICIPANTS: US employees at an information
      technology firm. INTERVENTIONS: Randomly selected clusters of managers and
      employees participated in a 3-month, social, and organizational change process
      intended to reduce work-family conflict. The intervention included interactive
      sessions with facilitated discussions, role playing, and games. Managers
      completed training in family-supportive supervision. MEASUREMENTS AND RESULTS:
      Primary outcomes of total sleep time (sleep duration) and wake after sleep onset
      (sleep quality) were collected from week-long actigraphy recordings at baseline
      and 12 months. Secondary outcomes included self-reported sleep insufficiency and
      insomnia symptoms. Twelve-month interviews were completed by 701 (93% retention),
      of whom 595 (85%) completed actigraphy. Restricting analyses to participants with
      e3 valid days of actigraphy yielded a sample of 473-474 for intervention
      effectiveness analyses. Actigraphy-measured sleep duration was 8 min/d greater
      among intervention employees relative to controls (P < .05). Sleep insufficiency
      was reduced among intervention employees (P = .002). Wake after sleep onset and
      insomnia symptoms were not different between groups. Path models indicated that
      increased control over work hours and subsequent reductions in work-family
      conflict mediated the improvement in sleep sufficiency. CONCLUSIONS: The
      workplace intervention did not overtly address sleep, yet intervention employees
      slept 8 min/d more and reported greater sleep sufficiency. Interventions should
      address environmental and psychosocial causes of sleep deficiency, including
      workplace factors.

PMID- 29073417
TI  - Evaluation of novel school-based interventions for adolescent sleep problems:
      does parental involvement and bright light improve outcomes?
AB  - OBJECTIVES: The current study aimed to evaluate school-based motivational sleep
      education programs (SEPs) with adjunct bright light therapy (BLT) and/or parental
      involvement (PI). DESIGN: Randomized controlled trial. SETTING: Six high schools,
      matched on socio-economic status (SES). PARTICIPANTS: A total of 193 adolescents
      (mean age, 16.3 +/- 0.4 years, 79%f). INTERVENTION: Classes were randomly
      assigned to (i) SEP + BLT, (ii) SEP + PI, (iii) SEP + BLT + PI, or (iv) classes
      as-usual (CAU). Sleep education programs involved 4*50 minute classes (over 4
      weeks) based on a Motivational Interviewing framework (Sleep Med 2011;12:246
      251). Students in BLT groups attempted a weekend phase advance using portable
      green light LED glasses (500 nm; 506 lux). Parents of PI groups watched a series
      of 4 YouTube clips (2-3 minutes in length) outlining their adolescent's learning
      in class and how they could assist. Students in the CAU groups continued their
      regular classes. MEASUREMENTS: Online questionnaires measuring sleep knowledge,
      sleep patterns (bedtime, sleep latency, total sleep time [TST], etc) and mood at
      preintervention and postintervention and 6-week follow-up. Intervention groups
      also completed a motivation-to-change questionnaire and provided qualitative
      feedback. RESULTS: Improvements in sleep knowledge (d = 0.59-0.88), sleep onset
      latency (d = 0.45-0.50), TST (d = 0.32-0.57), and mood (d = 0.24-0.46) were
      observed in all intervention groups relative to the CAU group. Similar
      improvements were observed in a subgroup of students identified as having delayed
      sleep timing (ie, sleep knowledge: d = 0.45-0.92; sleep onset latency: d = 0.59
      0.82; TST: d = 0.82-1.18). Increases in motivation to regularize out of bedtimes,
      obtain morning bright light (BLT groups), and avoid sleeping-in on weekends
      occurred (all P < .005). CONCLUSIONS: This motivational SEP produced meaningful
      and similar benefits for adolescents in all intervention groups. Longer BLT (ie,
      over school holidays) and more intensive parental inclusion should be
      investigated in future studies.

PMID- 29073418
TI  - Awakening a nation: A call to action.

PMID- 29073419
TI  - When sleep is intertwined with myth.

PMID- 29073420
TI  - Growth, feedback, and change.

PMID- 29073421
TI  - Sleep science and policy: a focus on school start times.

PMID- 29073422
TI  - Sleeping while disabled, disabled while sleeping.
AB  - This essay considers areas in which the study of sleep and sleep disorders might
      profit from the perspective of disability studies, as practiced in the humanities
      and social sciences. This interdisciplinary perspective considers the social and
      cultural dimensions of bodily and mental states and conditions that a particular
      society deems abnormal or impaired, as well as the lived consequences of those
      determinations. Some sleep disorders are considered disabilities, but almost all
      disabilities entail some disruption from normal sleeping patterns--whether
      because of physical pain, exhaustion, and emotional stress of facing obstacles in
      work and other areas of waking life, or challenging sleeping environments in
      which many disabled people live. Despite these disruptions, finding adequate
      nighttime care is often difficult for people with disabilities, and consequently,
      night is often when social isolation and vulnerability are most profound. In
      addition, caretakers themselves often find their own sleep profoundly disrupted,
      whether this occurs in a family setting or an institutional space. Finally, the
      essay suggests that a disability studies perspective can help us to see that
      disordered sleep--whether primary or secondary to a disabling condition--can both
      impact and be shaped by social relationships.

PMID- 29073423
TI  - Life shouldn't imitate art: infants need healthy and safe sleep environments.

PMID- 29073424
TI  - Sleep safe, my baby.

PMID- 29073425
TI  - Sleep duration and patterns in adolescents: correlates and the role of daily
      stressors.
AB  - OBJECTIVES: The first aim of this study was to assess the prevalence of sleep
      deficit in a large sample of adolescents. Second, the study aimed to assess
      whether short sleep duration in the sample was associated with emotional and
      behavioral problems. Lastly, the study aimed to investigate the association
      between daily stressors--bedtime activities and sleep duration. DESIGN: Cross
      sectional survey. SETTING: The questionnaires were completed during school hours
      in 17 municipal junior high schools in Sweden. PARTICIPANTS: A total of 2767
      adolescents aged 12 to 16 years, 48% girls. MEASUREMENTS AND RESULTS: Sleep
      measures included total sleep time (TST) for schooldays and weekends, obtained as
      combined measures of self-reported bed-time, wake-time, and sleep onset latency.
      We used the new National Sleep Foundation's guidelines to operationalize sleep
      duration. Overall 12% of younger adolescents (age 12-13 years) and 18% of older
      adolescents (14-16 years) slept less than recommended (TST < 7 hours).
      Adolescents reporting nonrecommended TST also reported more behavioral (ie, norm
      breaking behaviors) and emotional problems (ie, depression, anxiety, and anger),
      with effects in the small-medium range. Finally, adolescents reporting bedtime
      arousal and use of information and communication technology in bed were more
      likely to report TST < 7 hours. Stress at home (for younger adolescents) and
      stress of school performance (for older adolescents) were also associated with
      TST less than 7 hours. CONCLUSIONS: The new National Sleep Foundation's
      recommendations were informative in this context. Future sleep interventions need
      to target barriers to good sleep practices, such as use of information and
      communication technology, stress, and worry that may contribute to arousal at
      bedtime.

PMID- 29073426
TI  - Collaborating with obstetrical providers to promote infant safe sleep guidelines.
AB  - OBJECTIVES: To partner with obstetrical providers to increase promotion of the
      American Academy of Pediatrics guidelines for infant safe sleep. Specifically,
      this study evaluates the effectiveness of the Safe Sleep Toolkit during
      obstetrical visits. Secondary objectives include improving provider and maternal
      knowledge of safe sleep. METHODS: Obstetrical providers (n=11) and staff at an
      outpatient clinic were trained using the Safe Sleep Toolkit and encouraged to
      discuss infant safe sleep with pregnant women at their 28- or 36-week gestation
      appointment (n=111, 56 pre- and 55 post-intervention). Provider-reported time
      spent counseling women on safe sleep recommendations and safe sleep knowledge was
      measured before and after the intervention. Surveys were conducted with women
      assessing safe sleep knowledge, intention to follow guidelines, and whether safe
      sleep was discussed at the appointment. RESULTS: Significantly more post
      intervention women reported their provider had discussed safe sleep (78% vs 32%)
      (P<.001). Similarly, provider-reported discussion with women increased
      significantly for all safe sleep guidelines (82%-90% vs 8%-12%) (all P<.001).
      Maternal knowledge, especially surrounding unsafe sleep practices, improved
      significantly post-intervention. CONCLUSION: Training obstetricians to use a
      toolkit to promote infant safe sleep guidelines increases the prenatal delivery
      of this information, and improves pregnant women's knowledge and intentions
      regarding safe infant sleep.

PMID- 29073427
TI  - The role of psychiatric and somatic conditions in incidence and persistence of
      insomnia: a longitudinal, community study.
AB  - OBJECTIVE: The objective was to investigate the role of psychiatric and somatic
      conditions in incident and persistent insomnia. DESIGN: This was a prospective
      study with 3 measurement points over 1.5years. SETTING: The participants were
      sent a survey to their home addresses. PARTICIPANTS: A survey was sent out to
      5000 random individuals (18-70 years) in 2 Swedish counties. To those who
      returned the baseline questionnaire (n=2333), 2 follow-up surveys (6 and 18months
      later) were sent out and completed by 1887 and 1795 individuals, respectively.
      MEASUREMENTS: The survey contained questions about sociodemographic factors and
      insomnia symptomatology, the Hospital Anxiety and Depression Scale, and items
      assessing 12 forms of somatic conditions (eg, heart disease and headache).
      RESULTS: Baseline depression, headache, and number of psychiatric and somatic
      conditions were found to be independent risk factors for incident insomnia. Also,
      deterioration in depression and heart disease status and increased number of
      conditions over time increased the risk for insomnia incidence. Anxiety;
      depression; pain in neck, back, or shoulders; and headache at baseline were found
      to significantly discriminate between those with persistent insomnia and those
      with persistent normal sleep. Those with persistent insomnia also reported a
      higher number of conditions relative to those with persistent normal sleep. None
      of the psychiatric or somatic conditions were found to be associated with
      persistence of insomnia relative to remission of insomnia. CONCLUSION: The
      current study suggests that both psychiatric and somatic conditions are involved
      in the incidence but not in the persistence of insomnia. Clinical and theoretical
      implications of the results are discussed.

PMID- 29073428
TI  - Multiple phenotypes of resting-state cognition are altered in insomnia disorder.
AB  - BACKGROUND: Research has supported the role of cognitive processes in the
      development and maintenance of insomnia, yet a standardized characterization of
      mind-wandering experiences in insomniacs is lacking. OBJECTIVES: The aim was to
      understand the quantitative nature of thoughts and feelings during mind wandering
      in insomniacs and healthy controls and their relationship with sleep-related
      parameters. METHODS: We used the 5-minute eyes-closed wakeful rest as an
      experimental model condition of mind wandering. Forty-seven individuals with
      insomnia disorder according to the Diagnostic and Statistical Manual of Mental
      Disorders, Fifth Edition (48.66+/-15.62 years; 31 women) and 29 healthy controls
      (50.66+/-15.14 years; 17 women) participated in the experiments and completed the
      Amsterdam Resting-State Questionnaire (ARSQ) immediately after the resting
      session. Participants also completed the Insomnia Severity Index (ISI), the
      Pittsburgh Sleep Quality Index (PSQI), the Dysfunctional Beliefs and Attitudes
      About Sleep Scale (DBAS). Statistical analyses included multiple regression to
      elucidate the independent determinants of ARSQ phenotypes. RESULTS: Participants
      with insomnia presented higher ISI, PSQI, and DBAS scores than did healthy
      controls. Insomniacs had strikingly different scores on most dimensions of the
      ARSQ, in particular Discontinuity of Mind, Self, Sleepiness, and Health Concern,
      that correlated positively with ISI and DBAS. Multiple regressions highlighted
      that for insomniacs, ISI was the best predictor of both Discontinuity of Mind and
      Health Concern. CONCLUSIONS: Resting-state activity in insomnia is altered and it
      seems to be related to unhelpful beliefs and insomnia severity. Resting-state
      neuroimaging in combination with the ARSQ could reveal important associations
      between these aberrant cognitive scores and their underlying systems-level brain
      mechanisms.

PMID- 29073429
TI  - The association between acute stress-related insomnia and alcohol use.
AB  - OBJECTIVES: Despite contributing greatly to overall sleep disturbance,
      individuals suffering from sleep disorders, such as insomnia, may use alcohol
      because of a widely-held misconception that it will improve overall sleep quality
      and quantity. The purpose of this study was to examine the relationship between
      the motivations for drinking alcohol and acute stress-related insomnia. METHODS:
      Participants were 191 healthy individuals who were asked to complete an online
      questionnaire about stress-related insomnia, alcohol consumption, and motivations
      for drinking alcohol. RESULTS: Results revealed that individuals high in acute
      stress-related insomnia reported higher scores on measures of problem drinking
      behaviors and were more likely to report using alcohol as a means of reducing
      stress and facilitating sleep despite no difference in consumption rates.
      CONCLUSIONS: These findings represent an important factor for clinicians to
      consider when dealing with individuals reporting acute stress-related insomnia,
      particularly given the overall negative impact of alcohol on sleep quantity and
      quality, which may lead to an exacerbation of stress and insomnia.

PMID- 29073430
TI  - Common meanings of good and bad sleep in a healthy population sample.
AB  - OBJECTIVES: The study's purpose was to understand the common meanings and shared
      practices related to good and bad sleep from narratives of a sample of healthy
      participants. DESIGN: Interpretive phenomenology was the approach to analyze
      narratives of the participants' everyday experiences with sleep. Participants
      were interviewed and asked to describe typical good and bad nights' sleep, what
      contributes to their sleep experience, and the importance of sleep in their
      lives. Team interpretations of narratives identified common themes by consensus.
      SETTING: Medium sized city in New York State (upper west region). PARTICIPANTS: A
      sample of 30 healthy participants were from a parent study (n=300) on testing the
      sleep questions from the Behavioral Risk Factor Surveillance System from the
      Centers for Disease Control and Prevention. MEASUREMENTS/ANALYSIS:
      Interpretations of good and bad sleep. RESULTS: Participants described similar
      experiences of good and bad sleep often directly related to their ability to
      schedule time to sleep, fall asleep, and maintain sleep. Worrying about life
      stresses and interruptions prevented participants from falling asleep and staying
      asleep. Yet, based on current life priorities (socializers, family work focused,
      and optimum health seekers), they had differing values related to seeking sleep
      opportunities and strategizing to overcome challenges. CONCLUSIONS: The
      participants' priorities reflected the context of their main concerns and
      stresses in life that influenced the importance given to promoting sleep
      opportunities. Public health messages tailored to life priorities could be
      developed to promote healthy sleep practices.

PMID- 29073432
TI  - Henri Matisse: an image of sleep in a time of turmoil.

PMID- 29073431
TI  - Sleep Health: from idea to fruition.

PMID- 29073433
TI  - Realizing sleep health?

PMID- 29073434
TI  - What is sleep? Alan Alda and 20,000 kids want to know.

PMID- 29073436
TI  - Perceived neighborhood safety and sleep, commentary on the association of
      neighborhood characteristics with sleep duration and daytime sleepiness.

PMID- 29073437
TI  - Relationship between self-reported physical health problems and sleep
      disturbances among trauma survivors: a brief report.
AB  - OBJECTIVES: History of trauma exposure is often associated with negative physical
      health outcomes. Better understanding of this association may have important
      implications for improved health and decreased health care-related costs. One
      possible link between trauma and poor health outcomes is the pernicious impact of
      sleep disturbances. In the present study, it was hypothesized that sleep quality
      would predict physical health symptoms above and beyond posttraumatic stress
      disorder (PTSD) and depression. METHODS: Fifty-four trauma-exposed adults
      participated in a randomized controlled trial for treatment of trauma-related
      nightmares. Physical health symptoms, depression, PTSD symptoms, and sleep
      quality were assessed via self-report. RESULTS: Consistent with expectations,
      analyses revealed sleep quality uniquely contributed to physical health symptoms
      above and beyond PTSD and depression symptoms. Moreover, sleep quality mediated
      the relationship between PTSD symptoms and physical health symptoms. CONCLUSIONS:
      Findings suggest sleep disturbances may require specific interventions to
      maximize positive physical and mental health outcomes.

PMID- 29073438
TI  - Poor actigraphic and self-reported sleep patterns predict delinquency and daytime
      impairment among at-risk adolescents.
AB  - OBJECTIVE: To evaluate associations between actigraphic sleep patterns,
      subjective sleep quality, and daytime functioning (ie, sleepiness, symptoms of
      depression, and delinquency and other conduct problems) in at-risk adolescents.
      DESIGN: Prospective, observational cohort study. SETTING: Providence, RI,
      predominantly home and school and 2 visits to the Brown Center for the Study of
      Children at Risk. PARTICIPANTS: A diverse group of low-income 13-year-olds (n =
      49) with and without prenatal drug exposure. INTERVENTIONS: None. MEASUREMENTS:
      Actigraphy, sleep diaries, and sleep and health questionnaires. RESULTS: Above
      and beyond the effects of prenatal drug exposure and postnatal adversity,
      actigraphic daytime sleep was a significant predictor of daytime sleepiness and
      delinquency. Subjective sleep quality was a significant predictor of daytime
      sleepiness, delinquency, and depressive symptoms. Later bed times predicted
      increased delinquency. CONCLUSIONS: There was a unique effect of actigraphic
      daytime sleep duration, subjective nighttime sleep quality, and bedtime on
      daytime functioning (ie, sleepiness, symptoms of depression, and delinquency and
      other conduct problems) of at-risk adolescents. In these vulnerable youth, these
      problematic sleep patterns may contribute to feeling and behaving poorly.
      Intervention studies with at-risk teens should be conducted to further explore
      the role of these sleep parameters on daytime functioning.

PMID- 29073435
TI  - The association of neighborhood characteristics with sleep duration and daytime
      sleepiness.
AB  - BACKGROUND: Neighborhood characteristics have been linked to health outcomes.
      Various mechanisms link neighborhoods and health outcomes; sleep patterns may be
      1 contributor; however, little is known about the social determinants of
      disordered sleep. We examined the association of neighborhood characteristics
      with sleep duration and daytime sleepiness. METHODS: Participants (n = 801)
      enrolled as pairs (55 without pair), from 10 churches in the Stroke Health and
      Risk Education project; 760 were included for analysis (41 withdrew). Sleep
      duration (hours of sleep at night) and daytime sleepiness (adaptation of Berlin
      questionnaire; range, 0-3 [more daytime sleepiness]) were self-reported.
      Neighborhood characteristics included disadvantage, per capita violent crime
      (census tract level), and safety (self-reported and individual level). We fit
      generalized linear mixed models and multinomial and binomial logistic regression
      models to examine the associations between neighborhood characteristics and sleep
      outcomes while accounting for the clustering within churches and pairs, before
      and after adjustment for self-reported confounders (age, gender, income,
      education, body mass index, depressive symptoms, hypertension, and diabetes).
      RESULTS: The mean hours of sleep duration is 6.7 +/- 1.2, and the mean daytime
      sleepiness is 0.8 +/- 0.9. Neighborhood characteristics were not associated with
      sleep duration. Higher perceived neighborhood safety was associated with an 18.4%
      lower odds of daytime sleepiness in the unadjusted model (odds ratio, 0.82 [95%
      confidence interval, 0.69-0.96]). The association was attenuated in the fully
      adjusted model. Neighborhood disadvantage and violent crime were related to lower
      daytime sleepiness; however, associations were not statistically significant.
      CONCLUSION: Self-reported neighborhood safety was associated with lower daytime
      sleepiness. Future exploration of the pathways linking neighborhood
      characteristics and sleep is warranted.

PMID- 29073439
TI  - Short sleep duration as a risk factor for childhood overweight/obesity: a large
      multicentric epidemiologic study in China.
AB  - OBJECTIVES AND SETTING: The present study was designed to examine the association
      of sleep duration with obesity/overweight in a multicentric urban sample of
      Chinese children. PARTICIPANTS AND DESIGN: A random sample of 17,696 children
      aged 7.00-11.99 years participated in a cross-sectional multicentric survey.
      MEASUREMENTS: The Chinese version of the Children's Sleep Habits Questionnaire
      was used to collect information on children's sleep behaviors. Body mass index
      (BMI) was calculated as weight (kilograms)/height squared (square meters). Sex,
      age, and BMI were used to define overweight and obesity based on the definition
      recommended by the Working Group on Obesity in China. RESULTS: The prevalence of
      obesity and overweight in Chinese school-aged children was 10.7% and 10.3%,
      respectively. Hierarchical multiple linear regression models revealed a
      significant association between shorter sleep duration (hours/day) and increased
      BMI (beta = -0.120; P = .019). Multivariate logistic regression models
      demonstrated that, compared with sleep duration >=10 hours/d, mean sleep duration
      <9 hours/d experienced increased likelihood of overweight/obesity (odds ratio =
      1.21; P = .005). Moreover, sleep-schedule variability, independent of sleep
      duration, was found to be associated with overweight/obesity (odds ratio = 1.11;
      P = .016). CONCLUSIONS: Sleep duration and sleep-schedule variability, along with
      television viewing, homework schedule, and snack eating, were linked to
      overweight/obesity among elementary school children in this population-based
      sample.

PMID- 29073441
TI  - Too tired for school? The effects of insomnia on absenteeism in adolescence.
AB  - OBJECTIVES: Sleep has important consequences for a person's daytime functioning.
      Numerous studies have shown that insomnia predicts work absenteeism and work
      disability in adults, but only a few studies have examined this association in
      adolescents. This study aims to explore whether symptoms of insomnia in
      adolescents predict school absenteeism 1 year later, over and above known
      psychological risk factors for absenteeism. DESIGN: The study used a longitudinal
      design with 2 measurement points over 1 year. SETTING: The students completed
      questionnaires during school hours at baseline and again at follow-up.
      PARTICIPANTS: Students in the 10th to 12th grades in a Swedish upper secondary
      school were followed prospectively for 1 year (age, 16-20 years; N = 353; 48.1%
      girls). MEASUREMENTS AND RESULTS: We used logistic regression analyses,
      controlling for the known effects of psychological factors, and arrived at a
      model elucidating the role of insomnia. That is, besides symptoms of insomnia,
      the model included previous absenteeism, alcohol intoxication, school-related
      social phobia, social anxiety, depressive symptoms, somatic symptoms, and bully
      victimization. Symptoms of insomnia predicted school absenteeism 1 year later,
      over and above known risk factors for absenteeism. Adolescents reporting severe
      symptoms of insomnia were almost 3 times more likely than adolescents reporting
      no or low symptoms to report problematic absenteeism 1 year later. We did not
      find any gender difference. CONCLUSIONS: Our findings underscore the importance
      of sleep problems on adolescents' daytime functioning as measured by school
      absenteeism. Therefore, sleep may be an important target for preventive
      interventions with adolescents.

PMID- 29073440
TI  - Effects of the Young Adolescent Sleep Smart Program on sleep hygiene practices,
      sleep health efficacy, and behavioral well-being.
AB  - OBJECTIVES: Using a social learning model, the aim of the Sleep Smart Program was
      to primarily improve sleep health behaviors and secondarily improve academic
      performance and behavioral well-being. DESIGN: Randomized control trial for a
      social learning-based preventive intervention program. PARTICIPANTS: A diverse
      group of seventh graders from 2 urban, middle schools were randomly assigned,
      according to school, to an 8-session Sleep Smart Program (SS = 70) or a
      comparison group (comparison = 73). MEASUREMENTS: Sleep patterns, sleep hygiene,
      and sleep health efficacy; academic performance; and behavioral well-being were
      assessed at 4 times of measure (baseline, postintervention, 2 follow-up times in
      eighth grade). RESULTS: SS seventh graders experienced significantly greater
      sleep health efficacy, improved physiological and emotional sleep hygiene, more
      time in bed, and earlier bedtimes vs comparison group. SS (vs comparison)
      participants also reported a significant decrease in internalizing behavior
      problems and sustained academic performance. Finally, although not maintained at
      time 4, SS participants continued to report improved sleep health efficacy at
      time 3, whereas the comparison group participants' sleep health efficacy
      declined. CONCLUSION: The Sleep Smart preventive intervention was effective in
      improving sleep health efficacy, sleep hygiene, time in bed, and bedtimes; in
      maintaining grades; and in reducing internalizing behavior problems, yet these
      changes were not sustained at follow-up.

PMID- 29073442
TI  - Delay of first voiding episode is associated with longer reported sleep duration.
AB  - OBJECTIVES: Time to first void is a common outcome in nocturia clinical trials,
      but its relationship to other conventional self-reported sleep measures is
      uncertain. We examined associations between change in time to first void and
      change in sleep duration over the course of such a trial. METHODS: Secondary data
      analyses were based on a previously published study of a medication treating
      nocturia in 757 adult patients studied for periods up to 5 months. We used
      repeated-measures logistic regression models with generalized estimating
      equations (GEE) to examine the odds ratios (ORs) for achieving 6.0, 6.5, or 7.0
      hours of total sleep duration based on increases of time to first void of 1, 2,
      or 3 hours. RESULTS: Increases in time to first void were associated with longer
      sleep durations from beginning to end of study. A 1-hour increment in time to
      first void was associated with a higher likelihood of obtaining a total sleep
      duration of e6 (OR = 1.43; 95% confidence interval [CI], 1.19-1.73), e6.5 (OR =
      1.30; 95% CI, 1.16-1.47), or e7 (OR = 1.24; 95% CI, 1.12-1.37) hours, after
      controlling for baseline time to first void, baseline sleep duration, time, and
      age (all Ps < .0001). Similar results were seen for 2- and 3-hour increments in
      time to first void. CONCLUSIONS: Time to first void may be an important
      supplementary variable about which to inquire in population-based studies.

PMID- 29073443
TI  - Accuracy of self-reported sleep parameters compared with actigraphy in young
      people with mental ill-health.
AB  - OBJECTIVES: Validation of self-report assessment of habitual sleep duration and
      onset time in young people with mental ill-health. DESIGN: Validation sample.
      SETTING: Specialized early intervention centers for young people in Sydney,
      Australia. PARTICIPANTS: One hundred and forty-six young people with mental ill
      health. INTERVENTION: N/A. MEASUREMENTS: Self-reported habitual sleep duration
      and onset time were compared against at least 7 days of actigraphy monitoring.
      Average bias in and calibration of subjective measures were assessed, along with
      correlation of subjective and objective measures. Differences by age, sex, mental
      disorder type, and reported insomnia were also explored. RESULTS: On average,
      subjective estimates of sleep were unbiased. Overall, each additional hour of
      objective habitual sleep duration predicted 41 minutes more subjective habitual
      sleep duration, and each hour later objective habitual sleep onset occurred
      predicted a 43-minute later subjective habitual sleep onset. There were subgroup
      differences: subjective habitual sleep duration in self-reported insomnia was
      shorter than objective duration by 30 minutes (SD = 119), on average. Calibration
      of habitual sleep duration was worse for those with mood disorders than with
      other primary diagnoses (t = -2.39, P = .018). Correlation between subjective and
      objective measures was strong for sleep onset time (A = .667, P < .001) and
      moderate for sleep duration (r = .332, P < .001). For the mood disorder group,
      subjective and objective sleep durations were uncorrelated. CONCLUSIONS: Self
      reports seem valid for large-scale studies of habitual sleep duration and onset
      in help-seeking young people, but assessment of habitual sleep duration requires
      objective measures where individual accuracy is important.

PMID- 29073444
TI  - Erratum to Examining racial/ethnic disparities in the association between
      adolescent sleep and alcohol or marijuana use [Sleep Health 1 (2015) 104-108].

PMID- 29073445
TI  - Sorolla captures the sleep of a mother and newborn child.

PMID- 29073446
TI  - What parents want: parent preference regarding sleep for their preschool child
      when attending early care and education.
AB  - BACKGROUND: While most children cease napping between the ages of 2 and 5 years,
      across a range of international settings the allocation of a mandatory naptime is
      a common feature of the daily routine in Early Care and Education (ECE) programs
      for children of this age. Evidence regarding the developmental effects of napping
      is limited but, beyond age 2, is consistently associated with delayed night sleep
      onset and increased number of awakenings. OBJECTIVES: The present study examined
      parent preferences towards napping in ECE. METHODS: Participants were 750 parents
      of preschool-aged children attending a representative sample of Australian ECE
      programs across metropolitan, regional and rural sites in 2011. We analysed
      quantitative and open-ended questionnaire data from a large, longitudinal study
      of the effectiveness of Australian early education programs (E4Kids). Statistical
      analyses examined prevalence of parent preference for sleep and demographic
      correlates. Thematic analyses were employed to identify parents' rationale for
      this preference. RESULTS: The majority of parents (78.7%) preferred that their
      children did not regularly sleep while attending ECE. The dominant explanation
      provided by parents was that regular naps were no longer appropriate and
      adversely impacted their children's health and development. Parents of younger
      children were more likely to support regular naps. CONCLUSIONS: The results
      highlight a disjuncture between parent preferences and current sleep policy and
      practices in ECE. Further research is needed to establish evidence-based
      guidelines to support healthy sleep-rest practices in ECE. Such evidence will
      guide appropriate practice and support parent-educator communication regarding
      sleep and rest.

PMID- 29073447
TI  - Sleep health: focus on early care and education.

PMID- 29073448
TI  - Toddler naps in child care: associations with demographics and developmental
      outcomes.
AB  - OBJECTIVES: The objectives were to characterize the rate, duration, and factors
      associated with napping in a large, nationally representative sample of toddlers
      attending child care. DESIGN: We analyzed a subset of data from the nationally
      representative Early Childhood Longitudinal Study-Birth Cohort, including parent
      report, caregiver report, and observational measures. PARTICIPANTS: Data were
      limited to the 3050 participants reporting that their 2-year-old routinely spent
      greater than 1 hour per week in nonparental child care. MEASUREMENTS: Interviews
      were completed to measure child care type (relative, nonrelative, center-based),
      demographics, bedtime characteristics (eg, presence of a bedtime routine,
      assistance needed to fall asleep), and naptime. The Bayley Scales of Infant
      Development-Research Edition was used to measure child outcomes. RESULTS: Napping
      was reported to occur in 91% of 2-year-olds, with most naps reported to last 2
      hours. Significant racial and ethnic differences were found in nap duration, with
      black children napping longer and Latino children napping shorter than white
      children, controlling for socioeconomic status and sex. Children cared for by
      relatives had longer naps than those in nonrelative child care. There were no
      significant relationships between naps and child outcomes. CONCLUSIONS: Results
      highlight racial and ethnic differences in daytime napping duration and
      interesting differences in nap duration in different child care settings. Child
      care providers may use these results to adopt appropriate expectations, policies,
      and practices for 2-year-old napping.

PMID- 29073449
TI  - Supporting sleep in early care and education: an assessment of observed sleep
      times using a sleep practices optimality index.
AB  - AIM: The aim was to investigate whether the sleep practices in early childhood
      education (ECE) settings align with current evidence on optimal practice to
      support sleep. BACKGROUND: Internationally, scheduled sleep times are a common
      feature of daily schedules in ECE settings, yet little is known about the degree
      to which care practices in these settings align with the evidence regarding
      appropriate support of sleep. METHODS: Observations were conducted in 130
      Australian ECE rooms attended by preschool children (Mean=4.9years). Of these
      rooms, 118 had daily scheduled sleep times. Observed practices were scored
      against an optimality index, the Sleep Environment and Practices Optimality
      Score, developed with reference to current evidence regarding sleep scheduling,
      routines, environmental stimuli, and emotional climate. Cluster analysis was
      applied to identify patterns and prevalence of care practices in the sleep time.
      RESULTS: Three sleep practices types were identified. Supportive rooms (36%)
      engaged in practices that maintained regular schedules, promoted routine, reduced
      environmental stimulation, and maintained positive emotional climate. The
      majority of ECE rooms (64%), although offering opportunity for sleep, did not
      engage in supportive practices: Ambivalent rooms (45%) were emotionally positive
      but did not support sleep; Unsupportive rooms (19%) were both emotionally
      negative and unsupportive in their practices. CONCLUSIONS: Although ECE rooms
      schedule sleep time, many do not adopt practices that are supportive of sleep.
      Our results underscore the need for education about sleep supporting practice and
      research to ascertain the impact of sleep practices in ECE settings on children's
      sleep health and broader well-being.

PMID- 29073450
TI  - Sleep and behavior of preschool children under typical and nap-promoted
      conditions.
AB  - BACKGROUND: Children transition out of naps in early childhood. However, there is
      disagreement about when this transition should occur. AIMS: We compared measures
      of sleep and behavior in children divided into Frequent, Sometimes, and Rarely
      nappers to determine what factors predict when napping should cease. We then
      examined the effect of an experimenter-promoted nap on measures of sleep and
      behavior. METHODS: We studied 133 children (50.4% female; mean=52.77months) over
      16 days. Parents completed questionnaires, whereas children wore actigraphs. On 1
      study day, children were nap-promoted. RESULTS: Overnight sleep duration was
      significantly less for children who napped frequently than those who rarely
      napped, yet total 24-hour sleep and other sleep parameters did not differ across
      napping groups. Effortful control was marginally greater in those who rarely
      napped. Nap promotion was 91% successful across nap groups. When typical sleep
      was compared with sleep following a promoted nap, frequent nappers slept more on
      the nap-promoted night. Total 24-hour sleep increased in all children following
      the promoted nap, and other sleep parameters did not differ between groups.
      CONCLUSIONS: The emergence of self-regulatory behaviors may predict when children
      should cease napping, consistent with the hypothesis that transitioning out of
      naps may be related to brain maturation. Given previously reported benefits of
      sleep on cognition and the observed increase in 24-hour sleep following nap
      promotion, nap promotion may benefit early education. Further research should
      explore maturational cues that illuminate when children are ready to transition
      out of napping.

PMID- 29073451
TI  - Can we ever know the sleep of our ancestors?

PMID- 29073452
TI  - An intensive longitudinal examination of daily physical activity and sleep in
      midlife women.
AB  - OBJECTIVES: Previous research examining physical activity (PA) and sleep link has
      largely ignored the day-to-day variability that is present in these 2 health
      behaviors, and few studies have addressed this relation using objective
      assessments of PA and sleep. Through an intensive longitudinal design, the
      present study aimed: (1) to elucidate the reciprocal associations between PA and
      sleep; and (2) to better understand the role of body mass index (BMI) in these 2
      health behaviors. METHODS: Community-dwelling midlife women (N = 103; M = 53, age
      range= 40-60 years) wore an accelerometer for the objective assessment of PA and
      sleep for 21 days. A series of multilevel models were estimated to test
      concurrent and lagged associations between PA (activity counts, moderate-to
      vigorous PA) and sleep (total sleep time [TST], sleep efficiency, sleep
      fragmentation indices). RESULTS AND CONCLUSIONS: In concurrent, same-day
      analyses, a positive association emerged between PA and sleep such that as
      activity counts increased during the day, TST at night also increased (P < .05).
      In lagged analyses examining next-day effect of sleep on PA, a negative
      association was found such that greater TST on a given night was associated with
      less moderate-to-vigorous PA the subsequent day (P < .05). A moderation effect by
      BMI was also observed such that women with a high BMI engaging in overall lower
      levels of PA demonstrated poorer-quality sleep. The data suggest that leading a
      physically active lifestyle may have protective effects on sleep, particularly
      for overweight and obese women.

PMID- 29073453
TI  - Sleeping with technology: cognitive, affective, and technology usage predictors
      of sleep problems among college students.
AB  - OBJECTIVES: Sleep problems related to technology affect college students through
      several potential mechanisms including displacement of sleep due to technology
      use, executive functioning abilities, and the impact of emotional states related
      to stress and anxiety about technology availability. DESIGN: In the present
      study, cognitive and affective factors that influence technology usage were
      examined for their impact upon sleep problems. PARTICIPANTS AND MEASUREMENTS:
      More than 700 US college students completed an online questionnaire addressing
      technology usage, anxiety/dependence, executive functioning, nighttime phone
      usage, bedtime phone location, and sleep problems. RESULTS: A path model
      controlling for background variables was tested using the data. The results
      showed that executive dysfunction directly predicted sleep problems as well as
      affected sleep problems through nighttime awakenings. In addition,
      anxiety/dependence increased daily smartphone usage and also increased nighttime
      awakenings, which, in turn, affected sleep problems. CONCLUSIONS: Thus, both the
      affective and cognitive factors that influence technology usage affected sleep
      problems.

PMID- 29073454
TI  - Sleep: a human rights issue.

PMID- 29073455
TI  - Prospective associations between chronic youth sleep problems and young adult
      health.
AB  - OBJECTIVES: The current study investigated prospective associations between youth
      sleep problems across childhood and adolescence, as well as the relationship
      between chronic youth sleep problems and young adult health. Exploratory analyses
      investigated this sleep-health relationship in the context of several established
      risk factors, including youth depression and environmental stress. DESIGN: This
      project is an extension of the Mater-University Study of Pregnancy, a
      longitudinal study that followed more than 7000 children across early
      development. SETTING: Brisbane, Australia. PARTICIPANTS: Seven hundred ten mother
      child dyads assessed from birth to age 20. MEASUREMENTS: We used maternal report
      measures to assess the persistence of youth sleep problems. We used structural
      equation modeling to explore the relationship between chronic maternal-reported
      youth sleep problems and subjective reports of young adult health quality and to
      assess whether associations remained when other potential health risks were
      included in the model. RESULTS: Path analyses revealed that sleep problems in
      early childhood predicted sleep problems in middle adolescence, which predicted
      sleep problems at age 20. Structural equation models showed that chronic youth
      sleep problems predicted youth health quality at age 20 (beta = .263, P < .001)
      over and above the effects of early adversity, chronic childhood illness,
      maternal depression, lifetime youth depression, and chronic youth stress.
      CONCLUSIONS: Chronic sleep problems can emerge in childhood and may contribute to
      negative health outcomes in young adulthood. Chronic youth sleep problems remain
      a significant predictor of poor health when tested against other known health
      risk factors, suggesting that sleep may be an important health intervention
      target.

PMID- 29073456
TI  - Association of sleep duration with kidney function and albuminuria: NHANES 2009
      2012.
AB  - OBJECTIVE: The purpose of this study was to examine the association between self
      reported sleep duration and markers of kidney function. DESIGN: A cross-sectional
      survey from the 2009-2012 National Health and Nutrition Examination Survey.
      SETTING AND PARTICIPANTS: The participants were 8690 adults (e20years) without a
      previous sleep disorder diagnosis, end-stage kidney failure, or other kidney or
      liver problems. Subsamples with pre-diabetes and pre-hypertension were examined.
      MEASUREMENTS: Participants reported habitual sleep duration, coded as d5, 6, 7,
      8, and e9hours per night. Biomarkers of kidney function were determined,
      including glomerular filtration rate (eGFR) estimated from the Chronic Kidney
      Disease Epidemiology Collaboration equation, urine albumin-to-creatinine ratio
      (ACR), microalbuminuria status, and glomerular hyperfiltration status. Weighted
      and adjusted general linear models assessed associations between sleep duration
      with eGFR and ACR. Logistic regression analyses evaluated the associations of
      microalbuminuria and glomerular hyperfiltration status with sleep duration.
      RESULTS: Greater eGFR was related to short sleep duration in the total sample and
      among participants with pre-diabetes. Greater ACR was associated with short and
      long sleep duration. Short sleep duration (d5hours) was associated with an
      increased odds for glomerular hyperfiltration (OR, 1.41; 95% CI, 0.97-2.06) and
      microalbuminuria (OR, 1.31; 95% CI, 0.96-1.79). CONCLUSIONS: In a US
      representative sample of adults, self-reported short and long sleep duration were
      related to higher ACR. Short sleep duration was associated with higher eGFR and
      microalbuminuria. Research is needed to understand whether these associations
      indicate increased risk for kidney damage and cardiovascular risk.

PMID- 29073457
TI  - Insights from the OppNet initiatives on psychosocial stress and sleep: themes for
      multidisciplinary team science research.
AB  - Understanding the multilevel and bidirectional factors and basic mechanisms
      linking psychosocial stress, sleep, and their interactions to health outcomes is
      critical to building successful interventions and promoting population health. We
      report here on the first gathering of the National Institutes of Health Basic
      Behavioral and Social Sciences Research Opportunity Network grant recipients in
      the separate but interrelated topics of psychosocial stress and sleep. The
      meeting provided an opportunity for investigators to present their research
      methods and discuss emerging findings, gain insight into new research directions,
      and form innovative collaborations. Several recurring themes were identified:
      contextualizing behavioral processes as they unfold in the real world, developing
      and using novel measurement techniques, and looking over time and across the
      lifespan. The need for multidisciplinary team science was also identified as a
      key determinant of success. These themes suggest useful future research
      directions.

PMID- 29073458
TI  - Resting state fMRI correlates of Theory of Mind impairment in amyotrophic lateral
      sclerosis.
AB  - Theory of Mind (ToM), the ability to recognize thoughts and emotions of another,
      may be one of the cognitive domains affected in amyotrophic lateral sclerosis
      (ALS), a neurodegenerative disease now recognized as a multi-system disorder. The
      present study aimed to identify early dysfunctions of brain resting state
      functional magnetic resonance imaging (RS-fMRI) networks in a group of ALS
      patients longitudinally explored for impairment of "cognitive" and "affective"
      ToM subcomponents. RS-fMRI connectivity was investigated in a group of 21
      patients with ALS (i.e., 9 with bulbar-onset or ALS-B and 12 with limb-onset or
      ALS-L) in early stages of disease and 15 healthy controls (HCs). The same
      subjects were assessed, at baseline and after six months, for neuropsychological
      performances, including cognitive and affective ToM and multi-domain cognitive
      functions. The RS-fMRI study showed a decreased connectivity in frontotemporal
      areas within the main cognitive resting state networks, including the default
      mode (DMN), the right and left fronto-parietal (R-, L-FPN), and the salience
      (SLN) networks, in the entire ALS group. As exploratory results, comparing the
      ALS-B subgroup to the ALS-L one, we revealed a widespread decrease of RS-fMRI
      signals in the left middle frontal gyrus for L-FPN and SLN and in the left
      superior frontal gyrus for SLN. At baseline, no ToM or other cognitive
      abnormalities were reported in the entire group of ALS patients compared to HCs,
      although, after six months, the ALS-B subset exhibited a significant impairment
      of both affective and cognitive ToM subcomponents, whereas the ALS-L group showed
      significant impairment of the cognitive subcomponent alone. Our findings provide
      original evidence of the deficit of both ToM subcomponents during the ALS course,
      supporting the hypothesis of a biologically more aggressive character of ALS-B.
      Moreover, early RS-fMRI abnormalities in cognitive networks may underlie and
      precede the clinical appearance of ToM alterations in ALS.

PMID- 29073459
TI  - Physical aggressiveness and gray matter deficits in ventromedial prefrontal
      cortex.
AB  - What causes individuals to hurt others? Since the famous case of Phineas Gage,
      lesions of the ventromedial prefrontal cortex (VMPFC) have been reliably linked
      to physically aggressive behavior. However, it is unclear whether naturally
      occurring deficits in VMPFC, among normal individuals, might have widespread
      consequences for aggression. Using voxel based morphometry, we regressed gray
      matter density from the brains of 138 normal female and male adults onto their
      dispositional levels of physical aggression, verbal aggression, and sex,
      simultaneously. Physical, but not verbal, aggression was associated with reduced
      gray matter volume in the VMPFC and to a lesser extent, frontopolar cortex.
      Participants with less gray matter density in this VMPFC cluster were much more
      likely to engage in real-world violence. These findings suggest that even
      granular deficits in normal individuals' VMPFC gray matter can promote physical
      aggression.

PMID- 29073460
TI  - Quantification of Lactobacillus paracasei viable cells in probiotic yoghurt by
      propidium monoazide combined with quantitative PCR.
AB  - Propidium monoazide (PMA) coupled with qPCR has been successfully used for
      specific quantification of viable bacteria cells in diverse matrices food. The
      present study aimed to develop PMA-qPCR assay for quantification of Lactobacillus
      paracasei viable cells in probiotic yoghurt. L. paracasei grown in culture medium
      was submitted to heat treatment at 60 degrees C for different periods of time and
      probiotic yoghurt containing L. paracasei were prepared and stored at 4 degrees C
      for 30days. The viable cells were quantified using qPCR and PMA-qPCR assays
      targeting tuf gene and also by plate counting. Standard curves were prepared and
      mean efficiency obtained was 94% and 96% (R2>0.98) to L. paracasei in culture
      medium and probiotic yoghurt stored one day, respectively. The limit of detection
      (LOD) for both samples was 104 genome copies, corresponding to 32.1pg of DNA. For
      viable cells quantification, standard curves Cq versus log CFU were plotted using
      mean CFU by plate counting of L. paracasei grown in culture medium and probiotic
      yoghurt. Results obtained for L. paracasei heat-treated cells were concordant by
      PMA-qPCR and plate count, CFU decreased as the heat treatment time increased,
      while qPCR count remained constant. L. paracasei enumerations obtained by qPCR
      for probiotic yoghurt stored one day and 30days were higher than enumerations by
      PMA-qPCR for the same samples. The plate count values were similar to CFU values
      obtained by PMA-qPCR. These results showed that PMA-qPCR is a powerful approach
      compared with culture-dependent methods for quantification of L. paracasei viable
      cells in yoghurt. PMA-qPCR allowed reliable obtained results much faster than
      plate counting.

PMID- 29073461
TI  - Highly efficient synthesis of bioactive oleanane-type saponins.
AB  - Leveraging on Schmidt glycosylation method, a highly efficient approach to obtain
      oleanane-type triterpene saponins was fixed, whereby oleanyl mono-, disaccharide
      (guaianin N), trisaccharide (elatoside E), as well as tetrasaccharide (elatoside
      F) were obtained efficiently. The synthetic investigation has resulted in the
      discovery of the effect of branch-sugar incorporation sequence on the overall
      synthetic efficiency. Moreover, through bioactivity investigation, the cytotoxic
      activity of the obtained triterpenoid saponins was evaluated, and the preliminary
      structure-activity relationship was deduced.

PMID- 29073462
TI  - Implementing early mobilisation in the intensive care unit: An integrative
      review.
AB  - BACKGROUND: The intensive care unit provides complex care for critically ill
      patients. Consequently, due to the nature of critical illness and the therapies
      administered in intensive care, patients are often on prolonged periods of bed
      rest with limited mobility. It has been recognised that mobilising critically ill
      patients is beneficial to patients' recovery, however implementing early mobility
      as a standard of care remains challenging in practice. OBJECTIVES: To identify
      the key factors that underpin successful implementation and sustainability of
      early mobilisation in adult intensive care units. DESIGN: Integrative Review.
      DATA SOURCE: A systematic search strategy guided by SPICE framework (Setting,
      Perspective, Intervention, Comparison, Evaluation) was used to formulate the
      research question, identify study inclusion and exclusion criteria, and guide the
      database search strategy. Computerised databases were searched from August
      September 2016. Quality improvement articles that identified project
      implementation of early mobilisation of mechanically ventilated adult intensive
      care patients were included. REVIEW METHODS: After screening the articles,
      extracting project data and completing summary tables, critical appraisal of the
      quality improvement projects was completed using the Quality Improvement Minimum
      Quality Criteria Set. A modified version of the Cochrane Effective Practice and
      Organisation of Care taxonomy was used to synthesise the multifaceted
      implementation strategies the projects utilised to help bring about changes in
      clinician behaviour. RESULTS: Thirteen articles, reflecting 12 projects meeting
      the inclusion criteria were included in the final analysis. Eleven projects were
      conducted in the United States, and one in the United Kingdom. Quality scores
      ranged from 6 to 15. A formal framework to guide the quality improvement process
      was used in 9 projects. The three most frequently used groups of implementation
      strategies were educational meetings, clinical practice guidelines and tailored
      interventions. Managing the change process through strong leadership, designing
      strategies and interventions to overcome barriers to implementation,
      multidisciplinary team collaboration and data collection and feedback underpinned
      successful and sustainable early mobility practice change. CONCLUSION: The use of
      a quality improvement appraisal tool can help identify high quality projects when
      planning a similar mobility program. Even though projects were conducted in a
      variety of intensive care unit settings, and implementation frameworks and
      strategies varied, all began with strong leadership commitment to early
      mobilisation. This along with using the quality improvement process and
      multidisciplinary team approach ensured success and sustainability of mobilising
      ventilated patients.

PMID- 29073463
TI  - Inhibition of apoptosis in BHV-1-infected cells depends on Us3 serine/threonine
      kinase and its enzymatic activity.
AB  - Us3 protein is a serine/threonine kinase conserved within the Alphaherpesvirinae
      subfamily of herpesviruses. The Us3 homologs of herpes simplex virus,
      pseudorabies virus, and bovine herpesvirus type 5 have been shown to block
      apoptosis triggered by viral infection or exogenous inducers. To determine
      whether these characteristics are shared by bovine herpesvirus type 1 Us3, we
      constructed two viral mutants: BHV-1 Us3 deletion mutant (BHV-1DeltaUs3) and a
      kinase-dead mutant (BHV-1KD). Flow cytometry analysis and TUNEL assay clearly
      demonstrated, that only BHV-1 wild type virus suppressed infection-induced
      apoptosis and protected cells from apoptosis triggered by exogenous factors:
      sorbitol or staurosporine. Us3 of BHV-1 was directly capable of blocking
      apoptosis without the presence of other viral proteins. The presence of Us3
      correlated with phosphorylation of BAD, a pro-apoptotic Bcl-2 family member. Our
      results clearly indicate that BHV-1 Us3 is necessary for efficient blocking of
      apoptosis triggered by viral infection and exogenous factors.

PMID- 29073464
TI  - The impact of electrolyte on the adsorption of the anionic surfactant methyl
      ester sulfonate at the air-solution interface: Surface multilayer formation.
AB  - The methyl ester sulfonates represent a promising group of anionic surfactants
      which have the potential for improved performance and biocompatibility in a range
      of applications. Their solution properties, in particular their tolerance to hard
      water, suggests that surface ordering may occur in the presence of multi-valent
      counterion. Understanding their adsorption properties in a range of different
      circumstances is key to the exploitation of their potential. Neutron reflectivity
      and surface tension have been used to characterise the adsorption at the air
      aqueous solution interface of the anionic surfactant sodium tetradecanoic 2-sulfo
      1-methyl ester, C14MES, in the absence of electrolyte and in the presence of
      mono, di, and tri-valent counterions, Na+, Ca2+, and Al3+. In particular the
      emphasis has been on exploring the tendency to form layered structures at the
      interface. In the absence of electrolyte and in the presence of NaCl and CaCl2
      and AlCl3 at low concentrations monolayer adsorption is observed, and the
      addition of electrolyte results in enhanced adsorption. In the presence of NaCl
      and CaCl2 only monolayer adsorption is observed. However at higher AlCl3
      concentrations surface multilayer formation is observed, in which the number of
      bilayers at the surface depends upon the surfactant and AlCl3 concentrations.

PMID- 29073465
TI  - Mechanical stability, corrosion resistance of superhydrophobic steel and
      repairable durability of its slippery surface.
AB  - A simple way of chemical etching with H2SO4 and H2O2 was employed to prepare a
      superhydrophobic steel surface with a water contact angle of 163.5 degrees  and a
      sliding angle of about 0 degrees , in addition to modification with 1H,1H,2H,2H
      perfluoroalkyltriethoxysilane (FAS-13). On the basis of perfluropolyethers (PFPE)
      infusion, a slippery liquid-infused porous surface (SLIPS) was fabricated that
      had a water contact angle of 115.6 degrees  and a sliding angle of 2.27 degrees .
      The prepared sample can still maintain superhydrophobicity after moving 100 cm on
      1000 # sandpaper under 100 g loading via an abrasion test, while its corrosion
      resistance was exhibited via more positive corrosion potentials (Ecorr) and lower
      corrosion current densities (Icorr) in electrochemical corrosion tests with
      various solutions. Even if superhydrophobic and slippery properties were lost in
      the process of long-time soaking in salt solution, the superhydrophobic steel
      could regain its ability and slippery surfaces also exhibited the repairable
      durability through retreatment. Such stable, corrosion resistant and
      superhydrophobic bearing steel and repairable slippery surface have potential for
      application in practical production and life.

PMID- 29073466
TI  - Targeted photodynamic therapy of breast cancer cells using lactose-phthalocyanine
      functionalized gold nanoparticles.
AB  - Gold nanoparticles (AuNPs), which have been widely used for the delivery of
      photosensitizers for photodynamic therapy (PDT) of cancer, can be dispersed in
      aqueous solutions improving the delivery of the hydrophobic photosensitizer into
      the body. Furthermore, the large surface of AuNPs can be functionalized with a
      variety of ligands, including proteins, nucleic acids and carbohydrates, that
      allow selective targeting to cancer tissue. In this study, gold nanoparticles
      were functionalized with a mixed monolayer of a zinc phthalocyanine and a lactose
      derivative. For the first time, a carbohydrate was used with a dual purpose, as
      the stabilizing agent of the gold nanoparticles in aqueous solutions and as the
      targeting agent for breast cancer cells. The functionalization of the
      phthalocyanine-AuNPs with lactose led to the production of water-dispersible
      nanoparticles that are able to generate singlet oxygen and effect cell death upon
      irradiation. The targeting ability of lactose of the lactose-phthalocyanine
      functionalized AuNPs was studied in vitro towards the galectin-1 receptor on the
      surface of breast cancer cells. The targeting studies showed the exciting
      potential of lactose as a specific targeting agent for galactose-binding
      receptors overexpressed on breast cancer cells.

PMID- 29073467
TI  - Polymersomes at the solid-liquid interface: Dynamic morphological transformation
      and lubrication.
AB  - Polymersomes are hollow spheres self-assembled from amphiphilic block copolymers
      of certain molecular architecture. Whilst they have been widely studied for
      biomedical applications, relatively few studies have reported their interfacial
      properties. In particular, lubrication by polymersomes has not been previously
      reported. Here, interfacial properties of polymersomes self-assembled from
      poly(butadiene)-poly(ethylene oxide) (PBD-PEO; molecular weight 10,400 g mol-1)
      have been studied at both hydrophilic and hydrophobic surfaces. Their morphology
      at silica and mica surfaces was imaged with quantitative nanomechanical property
      mapping atomic force microscopy (QNM AFM), and friction and surface forces they
      mediate under confinement between two surfaces were studied using colloidal probe
      AFM (CP-AFM). We find that the polymersomes remained intact but adopted flattened
      conformation once adsorbed to mica, with a relatively low coverage. However, on
      silica these polymersomes were unstable, rupturing to form donut shaped residues
      or patchy bilayers. On a silica surface hydrophobized with a 19 nm polystyrene
      (PS) film, the polymer vesicles formed a more stable layer with a higher surface
      coverage as compared to the hydrophilic surface, and the interfacial structure
      also evolved over time. Moreover, friction was greatly reduced on hydrophobized
      silica surfaces in the presence of polymersomes, suggesting their potential as
      effective aqueous lubricants.

PMID- 29073468
TI  - Enhanced Escherichia coli inactivation and oxytetracycline hydrochloride
      degradation by a Z-scheme silver iodide decorated bismuth vanadate nanocomposite
      under visible light irradiation.
AB  - Novel Z-scheme AgI/BiVO4 photocatalysts were fabricated by a chemical deposition
      precipitation approach. The photocatalytic activities of the obtained catalysts
      were evaluated by disinfection of Escherichia coli (E. coli) and degradation of
      oxytetracycline hydrochloride (OTC-HCl) under visible-light irradiation. The BA3
      (contained 9.09% of AgI) exhibited the highest photocatalytic activity and
      maintained good stability. It could completely inactivate 7.0*107 CFU/mL of E.
      coli in 50 min and degrade 80% of OTC-HCl in 60 min. The enhanced photocatalytic
      activity of AgI/BiVO4 composites could be ascribed to the lower recombination
      rate of electron-hole pairs. Meanwhile, radical trapping experiments revealed
      that the superoxide radical (O2-) and holes (h+) were the dominant reactive
      species in photo-disinfection process. Furthermore, the effects of bacterial
      initial concentration and inorganic anions were also investigated to optimize the
      photocatalyst for practical application. This study will give a new insight to
      construct the effective Z-scheme system for bacterial inactivation and organic
      pollutants degradation.

PMID- 29073469
TI  - Top Bending Panicle1 is involved in brassinosteroid signaling and regulates the
      plant architecture in rice.
AB  - Brassinosteroids (BRs) regulate several aspects of plant growth and development.
      Although extensive studies have shown that BR signaling is conservative in higher
      plants, the molecular mechanism of regulating plant architecture in rice still
      remains to be explored. Here, we characterized a rice mutant named top bending
      panicle1 (tbp1). Compared to wild type, tbp1 mutant plants displayed semi-dwarf
      stature, erect leaves, small and round grains, as well as more tillers.
      Remarkably, the panicles of tbp1 plants were shorter and denser, and the tops of
      the panicles were curved by rolling of the base of flag leaves, which was later
      verified as due to reduced bulliform cell numbers. Map-based cloning, together
      with transgenic complementation and RNA-interference tests, revealed that TBP1 is
      a member of the somatic embryogenesis receptor kinases (SERKs) family involved in
      BR signaling. Furthermore, bimolecular fluorescence complementation and co
      immunoprecipitation analysis demonstrated that a substitution at 61st amino acid
      (His61Leu) in the tbp1 mutant may result in a reduction of the interaction
      between TBP1 and OsBRI1 (BR receptor in rice). Taken together, our results
      demonstrate that TBP1 plays a significant role in regulating plant architecture
      via the brassinosteroid signaling pathway.

PMID- 29073470
TI  - Comparative assessment of ceramic media for drinking water biofiltration.
AB  - Media type is a critical design consideration when implementing biofiltration for
      drinking water treatment. Granular activated carbon (GAC) has been shown to
      provide superior performance when compared to a wide range of media types,
      largely due to its higher surface area. Engineered ceramic media is an attractive
      alternative to GAC as it has a similar surface area but at a lower cost. This
      pilot-scale biofiltration study compared the performance of GAC, anthracite and
      two different effective sizes of ceramic (CER) media (1.0 mm and 1.2 mm), in
      terms of dissolved organic carbon (DOC), head loss, turbidity, and disinfection
      by-product formation potential (DBPFP). Biological acclimation was monitored
      using adenosine tri-phosphate (ATP) measurements; biomass was further examined
      using laccase and esterase enzyme activity assays. When compared to other media
      types examined, biological GAC had higher (p > 0.05) removals of DOC (9.8 +/-
      3.8%), trihalomethane formation potential (THMFP, 26.3 +/- 10.2%), and haloacetic
      acid formation potential (HAAFP, 27.2 +/- 14.0%). CER media required 6-7 months
      to biologically acclimate, while filters containing GAC and anthracite were
      biologically active (>100 ng of ATP/g media) following 30-45 days of operation.
      Once acclimated, ATP values of 243 and 208 ng/g attained for CER 1.0 and 1.2,
      respectively, were statistically comparable to GAC (244 ng/g) and higher than
      anthracite (110 ng/g), however this did not translate into greater organics
      removal. Esterase and laccase enzyme kinetics were highest for GAC, while CER was
      shown to have greater biodegradation potential than anthracite. The four media
      types attained similar turbidity reduction (p > 0.05), however ceramic media
      filters were observed to have run times which were 1.5-2.3 times longer when
      compared to anthracite, which could represent potential cost savings in terms of
      energy for pumping and backwash requirements. Overall, ceramic media was shown to
      be a potential alternative to anthracite when considering biofiltration,
      especially during cold water conditions (T < 10  degrees C).

PMID- 29073471
TI  - Prediction of sub-surface 37Ar concentrations at locations in the Northwestern
      United States.
AB  - The Comprehensive Nuclear-Test-Ban Treaty, which is intended to prevent nuclear
      weapon test explosions and any other nuclear explosions, includes a verification
      regime, which provides monitoring to identify potential nuclear explosions. The
      presence of elevated 37Ar is one way to identify subsurface nuclear explosive
      testing. However, the naturally occurring formation of 37Ar in the subsurface
      adds a complicating factor. Prediction of the naturally occurring concentration
      of 37Ar can help to determine if a measured 37Ar concentration is elevated
      relative to background. The naturally occurring 37Ar background concentration has
      been shown to vary between less than 1 mBq/m3 to greater than 100 mBq/m3
      (Riedmann and Purtschert, 2011). The purpose of this work was to enhance the
      understanding of the naturally occurring background concentrations of 37Ar,
      allowing for better interpretation of results. To that end, we present and
      evaluate a computationally efficient model for predicting the average
      concentration of 37Ar at any depth under transient barometric pressures. Further,
      measurements of 37Ar concentrations in samples collected at multiple locations
      are provided as validation of the concentration prediction model. The model is
      shown to compare favorably with concentrations of 37Ar measured at multiple
      locations in the Northwestern United States.

PMID- 29073472
TI  - Epilepsy may be the major risk factor of mental retardation in children with
      tuberous sclerosis: A retrospective cohort study.
AB  - Mental retardation (MR) is one of the most common cognitive comorbidities in
      children with tuberous sclerosis, and there are enormous studies about its risk
      factors. The genetic difference and the severity of epilepsy are the two main
      factors, but their weight in the occurrence of MR is still unclear. Two hundred
      twenty-three patients with tuberous sclerosis who received intelligence
      assessment, genetic mutation analysis, and the epilepsy severity assessment were
      included in our study. Genotype-neurocognitive phenotype correlations and
      epilepsy-neurocognitive phenotype correlations were analyzed by binary logistic
      regression analysis. No statistical significant result was found on genotype
      neurocognitive phenotype correlations, which contrasted the previous report. The
      prevalence of MR was 50.0% for the patients with tuberous sclerosis complex-1
      (TSC1) mutation, 54.5% for TSC2 (p=0.561), 54.7% for patients with protein
      truncating (PT) and 50.0% for patients with nontruncating (NT) (p=0.791), and
      54.3% for patients with family history and 53.7% for patients without family
      history (p=0.748). Statistical significant results were found on epilepsy
      neurocognitive phenotype correlations, both on E-chess score (p=0.01) and the
      occurrence of infantile spasms (p=0.014), which was consistent to the previous
      study. For children with tuberous sclerosis, instead of genetic factors, epilepsy
      may play the main role for the presence of mental retardation. Patients with
      mental retardation tend to have earlier seizure attack, take more AEDs, have more
      seizure types, and have higher seizure frequency. Among the four cognitive
      functions in Denver II, social ability and language ability are more vulnerable
      to be influenced than fine and gross motor ability.

PMID- 29073473
TI  - Functional hemispherectomy is safe and effective in adult patients with epilepsy.
AB  - INTRODUCTION: Functional hemispherectomy (FH) is a well-established therapeutic
      option for children with epilepsy with parenchymal damage confined to one
      hemisphere, yet its application in adults remains rare. The intention of our
      study was to investigate postoperative clinical and epileptological outcome in
      adults who received FH for intractable epilepsy. MATERIALS AND METHODS: We
      retrospectively analyzed 12 adult patients (18-56years) with intractable epilepsy
      due to unihemispheric pathology. All patients underwent FH. Postoperative
      neurological and cognitive outcome as well as seizure status were evaluated with
      a mean follow-up period of 4.9years. RESULTS: Ten patients (83%) were seizure
      free (Engel I), and two (17%) had recurrent seizures at last follow-up. Apart
      from one patient requiring operative revision for bone flap infection, no
      perioperative morbidity or mortality occurred. Postoperative functional
      assessment revealed deterioration of motor function in 7 patients, whereas 5
      remained unchanged. Language was unchanged in 8 patients. The absence of
      background slowing in preoperative electroencephalogram (EEG) as well as ictal
      and interictal EEG patterns located ipsilateral to the side of surgery was
      associated with favorable seizure outcome. CONCLUSION: Favorable seizure control
      and acceptable functional outcome can be achieved by FH in adults with
      intractable epilepsy. The risk of postoperative deficits is moderate and even
      older patients are able to manage postoperative motor impairment. Therefore, FH
      should be considered in case of unihemispheric lesions also in adults.

PMID- 29073474
TI  - Effects of continuous theta burst transcranial magnetic stimulation on cortical
      excitability in patients with idiopathic generalized epilepsy.
AB  - INTRODUCTION: Transcranial magnetic stimulation (TMS) is a noninvasive technique
      for investigating cortical physiologic functions in the brain. In this study, the
      effects of continuous theta burst stimulation (cTBS) on motor evoked potential
      (MEP) parameters in patients with idiopathic generalized epilepsy (IGE) were
      investigated. MATERIALS AND METHODS: Fifteen patients with IGE were included.
      Motor threshold (MT) and cortical silent period (CSP) were determined before cTBS
      application. Next, cTBS was applied to the dominant (left) hemisphere M1 hand
      area as the first application. After 1 day, cTBS was applied first to the left M1
      hand area and then to the right lateral cerebellar area as the second
      application. Parameters were again determined after the applications. RESULTS:
      There was no difference in resting MT values before and after cTBS application
      (p>0.05). Although CSP increased after stimulation (p<0.05), it was not
      significantly different between applications (p>0.05). CONCLUSION: For patients
      with epilepsy, cTBS is a safe technique when applied at a low intensity. The
      inhibitory effect of cTBS, a noninvasive technique, on cortical excitability in
      patients with IGE was determined using MEP parameters. The effect lasted at least
      1 h. To our knowledge, this is the first study to assess the effect of cTBS on
      cortical excitability in patients with IGE. Our findings indicate that cTBS
      decreases cortical excitability in patients with IGE.

PMID- 29073475
TI  - Structural differences in interictal migraine attack after epilepsy: A diffusion
      tensor imaging analysis.
AB  - OBJECTIVE: Patients with epilepsy (PWE) are more likely to suffer from migraine
      attack, and aberrant white matter (WM) organization may be the mechanism
      underlying this phenomenon. This study aimed to use diffusion tensor imaging
      (DTI) technique to quantify WM structural differences in PWE with interictal
      migraine. METHODS: Diffusion tensor imaging data were acquired in 13 PWE with
      migraine and 12 PWE without migraine. Diffusion metrics were analyzed using tract
      atlas-based spatial statistics analysis. Atlas-based and tract-based spatial
      statistical analyses were conducted for robustness analysis. Correlation was
      explored between altered DTI metrics and clinical parameters. RESULTS: The main
      results are as follows: (i) Axonal damage plays a key role in PWE with interictal
      migraine. (ii) Significant diffusing alterations included higher fractional
      anisotropy (FA) in the fornix, higher mean diffusivity (MD) in the middle
      cerebellar peduncle (CP), left superior CP, and right uncinate fasciculus, and
      higher axial diffusivity (AD) in the middle CP and right medial lemniscus. (iii)
      Diffusion tensor imaging metrics has the tendency of correlation with
      seizure/migraine type and duration. CONCLUSION: Results indicate that
      characteristic structural impairments exist in PWE with interictal migraine.
      Epilepsy may contribute to migraine by altering WMs in the brain stem. White
      matter tracts in the fornix and right uncinate fasciculus also mediate migraine
      after epilepsy. This finding may improve our understanding of the pathological
      mechanisms underlying migraine attack after epilepsy.

PMID- 29073477
TI  - Different in vitro cellular responses to tamoxifen treatment in
      polydimethylsiloxane-based devices compared to normal cell culture.
AB  - Cell culture systems based on polydimethylsiloxane (PDMS) microfluidic devices
      offer great flexibility because of their simple fabrication and adaptability.
      PDMS devices also make it straightforward to set up parallel experiments and can
      facilitate process automation, potentially speeding up the drug discovery
      process. However, cells grown in PDMS-based systems can develop in different ways
      to those grown with conventional culturing systems because of the differences in
      the containers' surfaces. Despite the growing number of studies on microfluidic
      cell culture devices, the differences in cellular behavior in PDMS-based devices
      and normal cell culture systems are poorly characterized. In this work, we
      investigated the proliferation and autophagy of MCF7 cells cultured in uncoated
      and Parylene-C coated PDMS wells. Using a quantitative method combining solid
      phase extraction and liquid chromatography mass spectrometry we developed, we
      showed that Tamoxifen uptake into the surfaces of uncoated PDMS wells can change
      the drug's effective concentration in the culture medium, affecting the results
      of Tamoxifen-induced autophagy and cytotoxicity assays. Such changes must be
      carefully analyzed before transferring in vitro experiments from a traditional
      culture environment to a PDMS-based microfluidic system. We also found that cells
      cultured in Parylene-C coated PDMS wells showed similar proliferation and drug
      response characteristics to cells cultured in standard polystyrene (PS) plates,
      indicating that Parylene-C deposition offers an easy way of limiting the uptake
      of small molecules into porous PDMS materials and significantly improves the
      performance of PDMS-based device for cell related research.

PMID- 29073476
TI  - CFTR potentiators: from bench to bedside.
AB  - One major breakthrough in cystic fibrosis research in the past decade is the
      development of drugs that target the root cause of the disease-dysfunctional CFTR
      protein. One of the compounds, Ivacaftor or Kalydeco, which has been approved for
      clinical use since 2012, acts by promoting the gating function of CFTR. Our
      recent studies have led to a gating model that features energetic coupling
      between nucleotide-binding domain (NBD) dimerization and gate opening/closing in
      CFTR's transmembrane domains (TMDs). Based on this model, we showed that ATP
      analogs can enhance CFTR gating by facilitating NBD dimerization, whereas
      Ivacaftor works by stabilizing the open channel conformation of the TMDs. This
      latter idea also explains the near omnipotence of Ivacaftor. Furthermore, this
      model identifies multiple approaches to synergistically boost the open
      probability of CFTR by influencing distinct molecular events that control gating
      conformational changes.

PMID- 29073478
TI  - Simultaneous determination and pharmacokinetics of fourteen bioactive compounds
      in rat plasma by LC-ESI-MS/MS following intravenous injection of Gegen-Sanqi
      compatibility solution.
AB  - A high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS)
      method was developed and fully validated for simultaneous determination of
      puerarin, 3'-hydroxy puerarin, 6"-O-xylosyl puerarin, 3'-methoxy puerarin,
      mirificin, puerarin-7-O-glucoside, daidzin, daidzein, daidzein-7-O-glucoside,
      ginsenoside-Rd, notoginsenoside-R1, ginsenoside-Re, ginsenoside-Rg1, ginsenoside
      Rb1 in rat plasma after intravenous injection of 5mL/kg Gegen-Sanqi compatibility
      solution (containing Pueraria flavonid 10.8mg/mL and Panax notoginsenosidum
      5.4mg/mL). After addition of internal standard (IS) baicalin, the analytes and IS
      were recovered from rat plasma by protein precipitation using acetonitrile
      containing 0.1% formic acid. Chromatographic separation was performed on a
      Capcell pak MG C18 column (3.0mm*75mm, 3.0MUm) at 35 degrees C with a flow rate
      of 0.75mL/min. Mass spectrometry was conducted using multiple reaction monitoring
      in positive mode. The method was linear for all of the analytes over 1000 times
      concentration range with correlation coefficients greater than 0.99. The
      precision and accuracy of the LC-MS/MS assay based on the three analytical
      quality control (QC) levels were well within the acceptance criteria from FDA
      guidance for bioanalytical method validation. Method recoveries were higher than
      75% and the matrix effects were minimal. All analytes were stable under tested
      conditions. It was the first time to study the pharmacokinetics of daidzein-7-O
      glucoside in rat plasma. To the best of our knowledge, this is the first study
      for simultaneous determination of so many analytes in rat plasma after
      intravenous injection of Gegen-Sanqi compatibility solution. It was expected that
      the present work would provide some helpful references for the apprehension of
      the mechanism of action and further clinical efficacy studies of Gegen-Sanqi herb
      pair.

PMID- 29073480
TI  - Rapid profiling and identification of puerarin metabolites in rat urine and
      plasma after oral administration by UHPLC-LTQ-Orbitrap mass spectrometer.
AB  - Puerarin, a bioactive natural C-glycoside isoflavonoid isolated from Pueraria
      lobata (Willd.) Ohwi, possesses many potential health benefits. However, the in
      vivo metabolic fates of puerarin have not been comprehensively clarified yet. In
      this study, an efficient strategy based on UHPLC-LTQ-Orbitrap mass spectrometer
      in both positive and negative ion modes was developed to profile and characterize
      puerarin metabolites in rat urine and plasma. Meanwhile, post-acquisition data
      mining methods including high-resolution extracted ion chromatogram (HREIC) and
      multiple mass defect filtering (MMDF) were utilized to screen potential puerarin
      metabolites from HR-ESI-MS1 stage. The mass fragmentation behaviors of five
      reference standards, including puerarin, daidzin, daidzein, genistin, and
      genistein, were comprehensively studied for construction of diagnostic product
      ions (DPIs), which could be employed to implement rapid identification of
      puerarin metabolites. Finally, a total of 66 metabolites (prototype compound
      included) were tentatively or positively identified based on standard substances,
      chromatographic retention times, accurate mass measurement, and corresponding
      ClogP values. Our results demonstrated that puerarin underwent multiple in vivo
      metabolic reactions including methylation, hydroxylation, dehydroxylation,
      hydrogenation, deglycosylation, glycosylation, sulfonation, glucuronidation, and
      their complicated reactions. In conclusion, the newly discovered puerarin
      metabolites significantly expanded the understanding on its pharmacological
      effects and built the foundation for further toxicity and safety studies.

PMID- 29073479
TI  - Acetonitrile extraction coupled with UHPLC-MS/MS for the accurate quantification
      of 17 heterocyclic aromatic amines in meat products.
AB  - This study proposed a simple and accurate acetonitrile extraction pretreatment
      method coupled with ultrahigh-performance liquid chromatography with tandem mass
      spectrometry for the simultaneous determination of 17 heterocyclic aromatic
      amines (HAAs) in meat products. With this new method, all 17 HAAs, including 11
      polar and 6 nonpolarHAAs, were simultaneously extracted by acetonitrile and
      purified by one-step Oasis MCX cartridge purification. Compared with two
      different improved reference methods, the acetonitrile method could obtain higher
      recoveries (in the range of 42.5% to 99.0%) and better repeatability (lower than
      12.2%). The limits of quantification were calculated between 0.028ngg
      1and0.648ngg-1 with high correlation coefficients (r>0.9976) in wide linear
      ranges. The proposed acetonitrile method was successfully applied to the analysis
      of the HAAs levels in 10 commercial meat products with satisfactory recoveries.

PMID- 29073481
TI  - Human placental growth hormone in ectopic pregnancy: Detection in maternal blood,
      immunohistochemistry and potential clinical implication.
AB  - OBJECTIVE: To investigate human placental growth hormone (hGH-V) in ectopic
      pregnancy (EP): detection in maternal blood, correlation with
      immunohistochemistry and possible role as a marker for the course of EP. DESIGN:
      Women presenting in the outpatient or emergency department of a tertiary care
      university hospital with a positive pregnancy test and strong suspicion of EP by
      ultrasound and/or symptoms were eligible for the study (n=70). Tissue specimens
      from the surgically treated patients (n=50) were examined by histopathology as
      well as by a hGH-V specific immohistochemistry set-up. A highly sensitive hGH-V
      specific immunoassay was used to analyse serum samples collected before
      treatment, day 1 post surgery samples and serial samples for medical treatment.
      RESULT(S): In EP patients' sera hGH-V was shown to be measurable for the first
      time (n=18). HGH-V however could not be detected in all patients' sera. HCG
      levels were significantly higher in the hGH-V serum positive group (p 0.001). HGH
      V was localized to the syncytiotrophoblast in all specimens of EP examined by
      immunohistochemistry (n=10) regardless of the detection in the patient's blood.
      CONCLUSION(S): Placental growth hormone (hGH-V) was shown to be present both in
      ectopic pregnancy patients' sera and tissue. It may serve as a biomarker for
      monitoring the course and treatment of EP.

PMID- 29073482
TI  - Care farms as a space of wellbeing for people with a learning disability in the
      United Kingdom.
AB  - People with a learning disability in the UK are increasingly choosing to spend
      their time on 'care farms' but there is limited research examining these spaces
      from their perspective. A qualitative research design was used to ask eighteen of
      these clients how care farms contributed to their health and wellbeing. For these
      participants care farms can be understood, using Fleuret and Atkinson's (2007)
      framework, as a 'space of wellbeing' and as a positive and life-enhancing space.
      Positive language was used by participants to describe the farms contrasting with
      ne gative language describing other spaces and activities. Farms were identified
      as contributing positively to mental and social wellbeing.

PMID- 29073483
TI  - Effect of ultrasound on dynamics characteristic of the cavitation bubble in
      grinding fluids during honing process.
AB  - The effect of ultrasound on generating and controlling the cavitation bubble of
      the grinding fluid during ultrasonic vibration honing was investigated. The
      grinding fluid on the surface of the honing stone was measured by utilizing the
      digital microscope VHX-600ESO. Based on analyzing the cavitation mechanism of the
      grinding fluid, the bubble dynamics model under conventional honing (CH) and
      ultrasonic vibration honing (UVH) was established respectively. Difference of
      dynamic behaviors of the bubble between the cases in UVH and CH was compared
      respectively, and the effects of acoustic amplitude and ultrasonic frequency on
      the bubble dynamics were simulated numerically using the Runge-Kutta fourth order
      method with variable step size adaptive control. Finally, the cavitation
      intensity of grinding fluids under ultrasound was measured quantitatively using
      acoustimeter. The results showed that the grinding fluid subjected to ultrasound
      can generate many bubbles and further forms numerous groups of araneose
      cavitation bubbles on the surface of the honing stone. The oscillation of the
      bubble under UVH is more intense than the case under CH, and the maximum velocity
      of the bubble wall under UVH is higher two magnitudes than the case under CH. For
      lower acoustic amplitude, the dynamic behaviors of the bubble under UVH are
      similar to that case under CH. As increasing acoustic amplitude, the cavitation
      intensity of the bubble is growing increased. Honing pressure has an inhabitation
      effect on cavitation effect of the grinding fluid. The perfect performance of
      cavitation of the grinding fluid can be obtained when the device of UVH is in the
      resonance. However, the cavitation intensity of the grinding fluid can be growing
      weakened with increasing ultrasonic frequency, when the device of UVH is in the
      off-resonance. The experimental results agree with the theoretical and numerical
      analysis, which provides a method for exploring applications of the cavitation
      effect in ultrasonic assisted machining.

PMID- 29073484
TI  - Droplet size prediction in ultrasonic nebulization for non-oxide ceramic powder
      synthesis.
AB  - Spray pyrolysis process has been used for the synthesis of non-oxide ceramic
      powders from liquid precursors in the Si/C/N system. Particles with a high
      thermal stability and with variable composition and size distribution have been
      obtained. In this process, the mechanisms involved in precursor decomposition and
      gas phase recombination of species are still unknown. The final aim of this work
      consists in improving the whole process comprehension by an
      experimental/modelling approach that helps to connect the synthesized particles
      characteristics to the precursor properties and process operating parameters. It
      includes the following steps: aerosol formation by a piezoelectric nebulizer, its
      transport and the chemical-physical phenomena involved in the reaction processes.
      This paper focuses on the aerosol characterization to understand the relationship
      between the liquid precursor properties and the liquid droplet diameter
      distribution. Liquids with properties close to the precursor of interest
      (hexamethyldisilazane) have been used. Experiments have been performed using a
      shadowgraphy technique to determine the drop size distribution of the aerosol.
      For all operating parameters of the nebulizer device and liquids used, bimodal
      droplet size distributions have been obtained. Correlations proposed in the
      literature for the droplet size prediction by ultrasonic nebulization were used
      and adapted to the specific nebulizer device used in this study, showing rather
      good agreement with experimental values.

PMID- 29073485
TI  - Acoustic source localization in anisotropic plates with "Z" shaped sensor
      clusters.
AB  - A new sensor cluster orientation is proposed to localize an acoustic source in a
      plate from the time difference of arrival (TDOA) with the help of only four to
      eight sensors. This technique requires neither a priori knowledge of the plate
      material properties nor a dense array of sensors to localize the acoustic source
      in isotropic as well as anisotropic plates. It is achieved by placing four
      sensors in a cluster in the shape of letter "Z" over a small region of the plate
      and a second Z-shaped cluster at another location of the plate. Experimental
      results show that it is possible to accurately localize the acoustic source with
      this new configuration. It reduces the number of sensors required for acoustic
      source localization in an anisotropic plate. Although one cluster in principle is
      capable of localizing the acoustic source in absence of any experimental error
      for accurate source localization in presence of experimental error two such Z
      shaped clusters are needed. In the currently available technique three L-shaped
      clusters having a total of 9 sensors are needed to achieve the same level of
      confidence in the acoustic source localization. Thus, the proposed new technique
      reduces the number of sensors by 1 (from 9 to 8) for confidently and accurately
      predicting the acoustic source.

PMID- 29073486
TI  - Capability evaluation of ultrasonic cavitation peening at different standoff
      distances.
AB  - Ultrasonic cavitation peening is a novel surface treatment technology which
      utilizes the effect of cavitation bubble collapses to improve the properties of
      metal surfaces. In order to obtain high impact during ultrasonic cavitation
      peening, a small standoff distance between a sound radiator and a rigid reflector
      (the surface of treated specimen) is necessary. However, the effects of different
      standoff distances on the capability of ultrasonic cavitation peening are not yet
      clear. In this paper, a simplified model was developed to evaluate the cavitation
      capability at different standoff distances. Meanwhile, to validate the
      theoretical model, the plastic deformation or erosion on the peening surface
      before and after treatment were compared. It was found that at a very small
      standoff distance the impact pressure generated by cavitation bubbles did not
      cause much deformation or erosion, as the dynamics of cavitation bubbles was
      limited. At a large standoff distance, due to much attenuation of sound
      propagation in the bubbly liquid, little impact pressure was generated by the
      collapse of cavitation bubbles and reached the treated surface. A fixed vibration
      amplitude, however, corresponded to a standoff distance which caused the largest
      deformation or erosion on the treated surface.

PMID- 29073487
TI  - Use of the reciprocity theorem for a closed form solution of scattering of the
      lowest axially symmetric torsional wave mode by a defect in a pipe.
AB  - Guided waves can effectively be used for inspection of large scale structures.
      Surface corrosion is often found as major defect type in large scale structures
      such as pipelines. Guided wave interaction with surface corrosion can provide
      useful information for sizing and classification. In this paper, the
      elastodynamic reciprocity theorem is used to formulate and solve complicated
      scattering problems in a simple manner. The approach has already been applied to
      scattering of Rayleigh and Lamb waves by defects to produce closed form solutions
      of amplitude of scattered waves. In this paper, the scattering of the lowest
      axially symmetric torsional mode, which is widely used in commercial
      applications, is analyzed by the reciprocity theorem. In the present paper, the
      theorem is used to determine the scattering of the lowest torsional mode by a
      tapered defect that was earlier considered experimentally and numerically by the
      finite element method. It is shown that by the presented method it is simple to
      obtain the ratio of amplitudes of scattered torsional modes for a tapered notch.
      The results show a good agreement with earlier numerical results. The wave field
      superposition technique in conjunction with the reciprocity theorem simplifies
      the solution of the scattering problem to yield a closed form solution which can
      play a significant role in quantitative signal interpretation.

PMID- 29073489
TI  - Procedural memory and speed of grammatical processing: Comparison between
      typically developing children and language impaired children.
AB  - BACKGROUND: Procedural memory has been proposed to underlie the acquisition of a
      range of skills including grammar, reading, and motor skills. In developmental
      language disorder (DLD) it has been suggested that procedural memory problems
      lead to the difficulties with grammar in this group. AIMS: This study aimed to
      extend previous research by exploring associations between procedural memory and
      a range of cognitive skills, in children with and without language impairments.
      METHODS AND PROCEDURES: Twenty children with DLD and 20 age-matched non-language
      impaired children undertook tasks assessing procedural memory, grammatical
      processing speed, single word and nonword reading, and motor skills (as indexed
      by a pegboard task). OUTCOMES AND RESULTS: For the DLD group, no significant
      correlations between procedural memory and any of the variables were observed.
      The typically developing group showed a significant correlation (r=.482, p<0.05)
      between the measure of procedural memory and grammatical processing speed.
      Correlations between procedural memory and the remaining variables were all non
      significant for this group. CONCLUSIONS AND IMPLICATIONS: This study provides new
      evidence showing that grammatical processing speed is correlated with procedural
      memory in typically developing children. Furthermore, results suggest that the
      relationship with procedural memory does not extend to reading or the types of
      motor skills used on a pegboard task. For the DLD group the pattern of result
      indicate grammatical processing, reading, and motor sequencing are not supported
      by procedural memory or a common memory system.

PMID- 29073488
TI  - Solid pseudopapillary tumor of the pancreas: clinical features and imaging
      findings.
AB  - This study aimed to report clinical features and CT, MRI, PET/CT findings of
      solid pseudopapillary tumor (SPT) of the pancreas. Thirty-four patients with
      pathologically proven SPT were retrospectively reviewed. Most patients were
      asymptomatic. SPTs in male patients mainly appeared as solid and near solid
      tumors. Mixed tumors and cystic tumors had larger size than solid and near solid
      tumors. Solid tumors and solid part of mixed tumors were T2 hyperintense and T1
      hypointense and had progressive enhancement. Four tumors (80%) showed markedly
      even or uneven 18F-FDG uptake. These characteristic features can help
      differentiate SPT from other pancreatic neoplasms.

PMID- 29073490
TI  - Exploring gender differences in the link between weight suppression and eating
      pathology.
AB  - Weight suppression (WS), the difference in one's highest weight (excluding
      pregnancy) and current weight at current height, is associated with the onset of
      eating disorders. Previous research has explored the influence of WS in
      predominantly clinical, female samples. However, the transition to college is a
      particularly high-risk time for weight gain and the development of eating
      pathology and men with eating disorders often have higher premorbid weights. This
      study investigated the associations of WS and dimensions of eating pathology in
      an undergraduate sample (N=859) and examined the effect of gender. Results
      demonstrated that higher levels of WS were associated with more dietary restraint
      (p=0.004) and more frequent purging behaviors (p<0.001); WS was indirectly
      related to loss-of-control eating through dietary restraint for both men and
      women (p<0.001). Additionally, men with higher WS were more likely to engage in
      extreme weight control behaviors, such as vomiting and laxative abuse (p=0.036).
      Findings suggest that weight history might be especially important to assess in
      men at risk for disordered eating. This approach might be particularly beneficial
      with college students due to their heightened risk of eating and weight
      disturbances.

PMID- 29073491
TI  - The influence of maltreatment history and out-of-home-care on children's language
      and social skills.
AB  - This study examined the extent to which maltreatment history and the
      characteristics of out-of-home care correlated with the language and social
      skills of maltreated children. Participants in this study were 82 maltreated
      children aged between 5 and 12 years of age. All children were residing with
      state-designated carers in out-of-home-care. The children were presented with
      standardised tests assessing language and social skills. Results showed that the
      sample performed significantly below the normative mean on both tests.
      Correlation analyses showed social skills, but not language skills were
      correlated with aspects of maltreatment history. The education level of the state
      designated carer/s was correlated with the children's language skills; higher
      education level was associated with higher language skills. The study provides
      evidence that at the group level, language and social skills are poor in
      maltreated children. However, gains in language skills might be made via the out
      of-home-care environment. Improvements in the social skills of maltreated
      children may require additional support.

PMID- 29073492
TI  - Tianeptine is associated with lower risk of suicidal ideation worsening during
      the first weeks of treatment onset compared with other antidepressants: A
      naturalistic study.
AB  - Worsening of suicidal ideation during the first weeks of antidepressant treatment
      is a poorly understood phenomenon that prompted regulatory bodies to issue
      specific warnings. To better understand the causes of this phenomenon, this study
      compared the risk of suicidal ideation worsening in patients taking different
      types of antidepressant medications. To this aim, 4017 depressed adult
      outpatients were followed by general practitioners and psychiatrists throughout
      France for 6 weeks after prescription of an antidepressant treatment. The main
      study outcomes were to monitor changes (worsening or improvement) in suicidal
      ideation between baseline (treatment onset) and the study end (week 6) and to
      determine the remission rates according to the treatment type. Depression
      severity was assessed with the patient-administered Hospital Anxiety and
      Depression Scale and suicidal ideation with the 9-item Montgomery-Asberg
      Depression Rating Scale and the Hopelessness Scale. Use of tianeptine, a mu
      opioid receptor agonist was significantly associated with a lower risk of
      suicidal ideation worsening compared with other antidepressants in the first 6
      weeks of treatment. Conversely, remission rates were not significantly affected
      by the treatment type. Our results highlight a potential interest of opioid
      agonists to reduce the risk of worsening of suicidal ideation at antidepressant
      initiation.

PMID- 29073493
TI  - The evaluation of the 1001.03 keV gamma emission absolute intensity using
      fundamental parameter method.
AB  - The accurate evaluation of the absolute intensity of the gamma-ray transition
      1001.03 keV of 234mPa is crucial for accurate determination of 238U in nuclear
      material and environmental samples. Over the last decades, a wide range of
      1001.03 keV absolute intensity values were published by different researchers and
      ranged from 0.59 to 1.12%. Nowadays, one of the most commonly used values is
      0.847 +/- 0.008% that seems not accurate and would eventually lead to an
      overestimation of 238U activity concentration. The absolute intensity of 1001.03
      keV gamma transition was re-evaluated using different fundamental parameter
      method (FPM) modes, uranium ore and granite samples, samples' geometries, sample
      to-detectors' geometries and gamma ray spectrometers. The mean +/- standard
      deviation of newly optimized absolute intensity value is 1.067 +/- 0.084% with an
      average relative bias of - 20% from the commonly used value.

PMID- 29073494
TI  - Information needs of patients with whiplash associated disorders: A Delphi study
      of patient beliefs.
AB  - BACKGROUND: Whiplash associated disorders (WAD) result in significant personal
      and economic costs. Patient education and reassurance are recommended treatments
      for acute WAD but the information needs of patients have not been investigated.
      OBJECTIVES: To determine what information whiplash-injured patients believe is
      important to help recovery in the acute stage of injury. DESIGN: A Delphi design
      survey series with three rounds. METHOD: Thirty-three participants who had
      sustained a whiplash injury within the last three years were invited to
      participate. Participants were asked to provide five statements, in response to
      an open-ended question, regarding what they believed was the most important
      information to provide to patients following a whiplash injury. Nineteen patients
      responded and 85 statements were collected and reviewed independently by two of
      the authors to remove duplicates. The importance of the remaining items was rated
      by the participants in the second survey round. Items rated by >50% of
      participants as important were included in the third survey round. To be deemed
      key information, >80% of participants had to rate an item as important in this
      final round. RESULTS: Eighteen items met the criteria for key information. These
      points addressed four areas: assessment and treatment, recovery and symptoms,
      patient attitudes during treatment and relationships with health practitioners.
      CONCLUSIONS: The key information points endorsed by patients in this study may
      provide useful information to constitute a basis for reassurance and education
      provided to patients with WAD. The results also suggest that improved
      relationships between patients with whiplash and health practitioners is
      required.

PMID- 29073495
TI  - What's up in the ALPS.
AB  - The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non
      infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune
      cytopenia. This clinical entity was recognized in the mid 60s and its genetic
      etiology was described in 1995 by the discovery of the FAS gene mutations. This
      was the first description of a monogenic cause of autoimmunity but its non
      Mendelian expression remained elusive until the description of somatic and
      germline mutations in ALPS patients. The related apoptosis defect accounts for
      the accumulation of autoreactive lymphocytes as well as for specific clinical and
      biological features that distinguish the ALPS-FAS from other monogenic causes of
      ALPS such as somatic mutations of RAS or the recently described CTLA-4
      insufficiency. The recognition of these genetic diseases brought new information
      on the regulation of the adaptive immune responses and uncovered new
      therapeutical targets. Finally, the deciphering the role of somatic mutations may
      pave the way to the understanding of more common autoimmune diseases.

PMID- 29073496
TI  - Experimental study and numerical simulation on the structural and mechanical
      properties of Typha leaves through multimodal microscopy approaches.
AB  - The Typha leaf, with special multi-level structure, low density and excellent
      mechanical properties, is an ideal bionic prototype utilized for lightweight
      design. In order to further study the relationship between the structure and
      mechanical properties, the three-dimensional macroscopic morphology of Typha
      leaves was characterized by micro computed tomography (Micro-CT) and its internal
      microstructure was observed by scanning electron microscopy (SEM). The
      combination of experimental and computational research was carried out in this
      paper, to reveal and verify the effect of multi-level structure on the mechanical
      properties. A universal testing machine and a self-developed mechanical testing
      apparatus with high precision and low load were used to measure the mechanical
      properties of the axial compression and lateral bending of the leaves,
      respectively. Three models with different internal structures were established
      based on the above-mentioned three-dimensional morphologies. The result
      demonstrated that the structure of partitions and diaphragms within the Typha
      leaf could form a reinforcement ribs structure which could provide multiple load
      paths and make the process of compression and bending difficult. The further
      nonlinear finite element analysis through LS-DYNA proved that internal structure
      could improve the ability of the models to resist compression and deformation.
      The investigation can be the reference for lightweight thin-walled structure
      design and inspire the application of the bionic structural materials.

PMID- 29073497
TI  - Therapeutic approaches for protecting bone health in patients with breast cancer.
AB  - Improvements in the survival of patients with breast cancer, together with a
      better understanding of the pathology of the disease, have led to the emergence
      of bone health as a key aspect of patient management. Patients with breast cancer
      are typically at risk of skeletal complications throughout their disease course.
      The receptor activator of nuclear factor kappa B ligand (RANKL) inhibitor
      denosumab and bisphosphonates (e.g. zoledronic acid) are approved in Europe for
      the prevention of skeletal-related events (pathologic fracture, radiation or
      surgery to bone, and spinal cord compression) in adults with bone metastases
      secondary to solid tumours. These agents are also approved at lower doses for the
      treatment of patients with postmenopausal osteoporosis, a population largely
      overlapping with those in the early stages of breast cancer, and those with
      cancer treatment-induced bone loss, which is caused primarily by aromatase
      inhibitors. In this review, we consider the evidence supporting the use of
      therapeutic agents to protect bone health throughout the course of breast cancer.
      Timing of treatment initiation, dose and treatment duration may prove to be
      barriers to the optimization of the practical use of these agents in the
      management of patients with breast cancer. Furthermore, with longer survival
      times, patients may expect to receive long-term treatment with denosumab or
      bisphosphonates, therefore consideration must be given to safety. Thus, we aim to
      summarize the recommendations for the use of these agents in management of
      patients with breast cancer in Europe. We also discuss the recent evidence for
      their potential antineoplastic effects.

PMID- 29073499
TI  - Management of major vascular injury during pedicle screw instrumentation of
      thoracolumbar spine.
AB  - OBJECTIVES: Vascular injury is a rare complication of spinal instrumentation.
      Presentation can vary from immediate hemorrhage to pseudoaneurysm formation. In
      the literature, surgical approach to repair has varied based on anatomy, acuity
      of diagnosis, infection, and available technology. In this manuscript, we aim to
      describe our institutional experience with vascular injuries in thoraco-lumbar
      spine surgery. PATIENTS AND METHODS: We report our institutional experience of
      three cases of vascular injury secondary to pedicle screw misplacement and their
      management, as well as a review of the literature. RESULTS: The first case had a
      history of previous instrumentation and presented with back pain and fever. The
      patient was taken for instrumentation exploration via a posterior approach.
      Aortic violation was discovered at T6 intraoperatively during instrumentation
      removal and the patient underwent emergent endovascular repair. The second case
      presented with chronic back pain after multiple prior posterior fusions and CT
      angiogram showing screw perforation on the aorta at T10. The patient underwent
      elective endovascular repair with synchronous removal of the instrumentation. The
      third case presented with radicular leg pain 6 months after L4-S1 posterior
      lumbar interbody fusion, with CT scan demonstrating the left S1 screw abutting
      the L5 nerve root and common iliac vein. The patient underwent elective
      instrumentation revision with intraoperative venography. CONCLUSION: Major
      vascular injury is a known complication of spinal surgery, especially if it
      involves instrumentation with pedicle screws. Treatment approach has evolved with
      the advancement of endovascular technology; however, open surgery remains an
      option when anatomy or infection is prohibitive. In the elective setting,
      preoperative planning with attention to surgical approach, positioning, and
      contingencies, should occur in a multidisciplinary fashion. Repair with an aortic
      stent-graft cuff may minimize unnecessary coverage of the descending thoracic
      aorta and intercostal arteries.

PMID- 29073498
TI  - External validation of Modified Breast Graded Prognostic Assessment for breast
      cancer patients with brain metastases: A multicentric European experience.
AB  - BACKGROUND: Several prognostic scores have been developed to estimate survival of
      breast cancer (BC) patients with brain metastases (BM). Modified Breast Graded
      Prognostic Assessment (GPA), based on a single-institution cohort of 1552
      patients, has been proposed as refinement of Breast-GPA. In addition to age,
      tumour subtype and KPS, Modified Breast-GPA comprises number of BM. This study
      was designed to validate Modified Breast-GPA. PATIENTS AND METHODS: Clinical data
      of 668 BC patients diagnosed with BM at four institutions between 1996 and 2016
      were reviewed. Patients were classified by Breast-GPA and Modified Breast-GPA.
      Overall survival (OS) was calculated from time of BM diagnosis to death or last
      follow-up. Cox proportional models were used to calculate hazard-ratios and their
      95% CI. The performances of Breast-GPA and Modified Breast-GPA were compared
      using Harrell's concordance index. RESULTS: Median age at BM diagnosis was 56
      years (range 24-85). At last follow-up, 632 patients (94.6%) had died. Median OS
      was 8.1 months (95% CI 6.9-9.4). The number of BM (1-3 vs. >3) was significantly
      associated with OS in univariate analysis (p < 0.001) and having >3 BM was
      identified as a negative prognostic factor in multivariate analysis. Both Breast
      GPA and Modified Breast-GPA accurately predicted OS (p < 0.001 for both scores).
      Performance of Modified Breast-GPA was better: concordance indices were 0.6390
      (95% CI, 0.6381 to 0.6399) and 0.6647 (95% CI, 0.6639 to 0.6655) for Breast-GPA
      and Modified Breast-GPA, respectively (p < 0.001). CONCLUSIONS: This work
      provides the first external independent validation of Modified Breast-GPA and
      confirms its better performance as compared to Breast-GPA.

PMID- 29073500
TI  - Precision surgery of rolandic glioma and insights from extended functional
      mapping.
AB  - OBJECTIVES: Electrical cortical stimulation mapping (ECSM) is the current gold
      standard functional mapping technique; however, it is burdened by several
      limitations. Our objective in this study is to show that extended functional
      mapping modalities can (1) allow neurosurgeons to map and preserve eloquent
      regions that are inaccessible by the traditional ECSM technique and (2) factor
      into the operative decision-making process and surgical trajectory during
      resection of Rolandic brain tumors. PATIENTS AND METHODS: A 55year old patient
      having a right Rolandic glioblastoma underwent subdural grid implantation
      followed by surgical resection. Multimodal functional mapping including
      electrical stimulation, high gamma power mapping, functional magnetic resonance
      imaging, and diffusion tensor imaging were performed to define the location of
      the patient's eloquent cortex and white matter tracts in relation to the tumor
      and determine the optimal surgical trajectory prior to resection. RESULTS: The
      patient tolerated a safe surgical resection without any new postoperative
      deficits. ECSM mapping successfully delineated safe areas for resection as well
      as eloquent areas related to motor control and speech production. High gamma
      power analysis successfully mapped areas involved in arm reach. Functional MRI
      showed the regions related to finger tapping. DTI demonstrated the corticospinal
      tract and its relation to the hand motor cortex and the tumor. CONCLUSION:
      Adjunct mapping techniques used to supplement the data offered by ECSM can help
      advance the field of functional mapping and Rolandic surgery via broadening our
      accessibility to the human brain and providing a comprehensive map of eloquent
      grey and white matter structures and their relation to the tumor.

PMID- 29073501
TI  - Nerve transfer to relieve pain in upper brachial plexus injuries: Does it work?
AB  - OBJECTIVES: Patients with C5 and C6 nerve root avulsion may complain from pain.
      For these patients, end-to-side nerve transfer of the superficial radial nerve
      into the median nerve is suggested to relieve pain. PATIENTS AND METHODS: Eleven
      patients (with a primary brachial plexus reconstruction) undergoing end-to-side
      nerve transfer of the superficial radial nerve into the ulnovolar part of the
      median nerve were assessed. Pain before surgery was compared to that at 6-month
      follow-up using visual analog scale (VAS) scores. RESULTS: A significant
      difference was seen between the mean VAS before (8.5) and after surgery (0.7)
      (P=0.0). After the six-month follow-up, 6 patients felt no pain according to VAS,
      notwithstanding 5 patients with a mild pain. CONCLUSION: The evidence from the
      present study suggests that end-to-side nerve transfer of the superficial radial
      nerve into the ulnovolar part of the median nerve is an effective technique in
      reducing pain in patients with C5 and C6 nerve root avulsion.

PMID- 29073502
TI  - The growth of a stable stationary structure: coordinating cell behavior and
      patterning at the shoot apical meristem.
AB  - Plants are characterized by their ability to produce new organs post
      embryonically throughout their entire life cycle. In particular development of
      all above-ground organs relies almost entirely on the function of the shoot
      apical meristem (SAM). The SAM performs a dual role by maintaining a pool of
      undifferentiated cells and simultaneously driving cell differentiation to
      initiate organogenesis. Both processes require strict coordination between
      individual cells which leads to formation of reproducible morphological and
      molecular patterns within SAM. The patterns are formed and maintained in large
      part due to spatio-temporal variation in signaling of plant hormones auxin and
      cytokinin resulting in tissue-specific transcriptional regulation. Integration of
      these mechanisms into computational models further identifies the key regulatory
      interactions involved in SAM function.

PMID- 29073503
TI  - Euglenoid pellicle morphogenesis and evolution in light of comparative
      ultrastructure and trypanosomatid biology: Semi-conservative microtubule/strip
      duplication, strip shaping and transformation.
AB  - Uniquely in eukaryotes, euglenoid pellicles comprise longitudinal proteinaceous,
      epiplasmic strips underlain by microtubules. Contradictory interpretations of
      pellicle microtubule duplication and segregation assumed opposite microtubule
      polarity from kinetoplastid Euglenozoa and conservative microtubule segregation.
      Distigma shows new pellicle microtubules nucleating posteriorly as in
      trypanosomatids, unifying euglenoid and kinetoplastid pellicle morphogenesis, but
      strip-growth is unpolarised. Epiplasmic insertion and cutting make new strip
      junctions between alternating wide and narrow daughter strips that grow
      intussusceptively. Nanotubules, overlooked epiplasm-associated components, define
      strip edges. At strip heel/toe junctions all euglenoids have a morphogenetic
      centre microtubule mt2/3 pair. Arguably, proteolysis, epiplasmic growth, and toe
      nanotubule-associated epiplasmic scission initiate daughter strips, separating
      old mts2/3; new mt2/3/bridge-B assembly, sub-heel scission, nanotubule-bridge-A
      assembly complete duplication. Only mt2/3 pair fully enters the canal, one master
      microtubule also the reservoir, other pellicle microtubules terminating near
      canal rims. A related cytokinesis model involving ciliary attachment zone
      duplication explains near-universally even spirocute strip number. I consider
      Serpenomonas and Entosiphon alternating heteromorphic strips developmental stages
      of 'strip transformation'; explain intergroup diversity of strip morphology and
      dorsoventral strip differentiation causally by specific pellicle-complex
      components; propose centrin-based mechanisms for strip shaping and euglenoid
      movement; unify pellicle cytokinetic microtubule segregation across Euglenozoa;
      and discuss origin and diversification of pellicle complexes.

PMID- 29073504
TI  - A highly versatile automatized setup for quantitative measurements of PHIP
      enhancements.
AB  - The design and application of a versatile and inexpensive experimental extension
      to NMR spectrometers is described that allows to carry out highly reproducible
      PHIP experiments directly in the NMR sample tube, i.e. under PASADENA condition,
      followed by the detection of the NMR spectra of hyperpolarized products with high
      spectral resolution. Employing this high resolution it is feasible to study
      kinetic processes in the solution with high accuracy. As a practical example the
      dissolution of hydrogen gas in the liquid and the PHIP kinetics during the
      hydrogenation reaction of Fmoc-O-propargyl-l-tyrosine in acetone-d6 are
      monitored. The timing of the setup is fully controlled by the pulse-programmer of
      the NMR spectrometer. By flushing with an inert gas it is possible to efficiently
      quench the hydrogenation reaction in a controlled fashion and to detect the
      relaxation of hyperpolarization without a background reaction. The proposed
      design makes it possible to carry out PHIP experiments in an automatic mode and
      reliably determine the enhancement of polarized signals.

PMID- 29073505
TI  - Coping strategies of internally displaced women in Georgia: A qualitative study.
AB  - There is limited evidence on the coping strategies of conflict-affected civilians
      in low and middle income countries. The aim of this paper is to explore the
      coping strategies used by women internally displaced within the Republic of
      Georgia due to the Russo-Georgian war in 2008. We use a five-fold coping typology
      to examine coping strategies in the accounts of 42 Georgian women residing in
      internally-displaced persons settlements. Semi-structured interviews were
      conducted during fieldwork in Georgia from December 2012 to February 2013.
      Problem solving and support seeking behaviours emerged as the most-commonly-used
      strategies. The findings suggest interventions fostering sustainable livelihoods
      and robust social networks are needed to utilise the coping strategies commonly
      used by internally displaced women in Georgia.

PMID- 29073506
TI  - The oughtness of care: Fear, stress, and caregiving during the 2000-2001 Ebola
      outbreak in Gulu, Uganda.
AB  - In this article we introduce the term oughtness of care to show how caring for
      sick relatives was experienced in the context of the Ebola outbreak in Gulu,
      Uganda, in 2000-2001. We conducted fieldwork over a nine month period from July
      2016 to March 2017 in the suburbs of Lacor, Bardege, Pece Lukung, Kasubi, Limu,
      and Kanyagoga Koro Layibi, Rwot Obilo, all of which were epicenters for Ebola. In
      addition, we conducted interviews in the districts of Amuru, Kitgum, and Lamwo,
      where some interlocutors had resettled following the end of the war that was
      affecting Gulu at the time of the Ebola outbreak. Of the 198 interlocutors in the
      focus group discussions, we followed up on 98 for further group and individual
      interviews. Our analysis principally provides a retrospective ethnographic study
      of caregivers' moral experiences of the need to care for sick relatives during
      the outbreak. In our study, respondents argued that they would rather respond to
      the compelling need to offer care for intimate others at home or in a healthcare
      institution, rather than listen to sensitization messages not to touch sick
      patients. We introduce the term oughtness of care to enable us to understand how
      caregiving, which caregivers experienced as a moral logic draws its justification
      from the specific situation of radical insecurity which they were thrown into. We
      argue that this caregiving has its own logic, which is insufficiently captured by
      conventional public health approaches to containing Ebola outbreaks. Caregivers
      are, in consequence, not recognized as ethical subjects by such public health
      interventions. By providing an understanding of the moral experience of
      caregiving and the distinct logic of care, our analysis contributes to the
      development of relevant and effective public health responses to Ebola epidemics.

PMID- 29073507
TI  - Effects of state-level Earned Income Tax Credit laws in the U.S. on maternal
      health behaviors and infant health outcomes.
AB  - The purpose of this paper is to investigate the effects of state-level Earned
      Income Tax Credit (EITC) laws in the U.S. on maternal health behaviors and infant
      health outcomes. Using multi-state, multi-year difference-in-differences
      analyses, we estimated effects of state EITC generosity on maternal health
      behaviors, birth weight and gestation weeks. We find little difference in
      maternal health behaviors associated with state-level EITC. In contrast, results
      for key infant health outcomes of birth weight and gestation weeks show small
      improvements in states with EITCs, with larger effects seen among states with
      more generous EITCs. Our results provide evidence for important health benefits
      of state-level EITC policies.

PMID- 29073508
TI  - Lower limbs venous compression reduces the incidence of maternal hypotension
      following epidural analgesia during term labor.
AB  - OBJECTIVE(S): Every year in France, 10% to 20% of the 600 000 women given
      epidural analgesia during labor experience hypotension, which in 15% of cases is
      associated with fetal heart rate abnormalities. The efficiency of lower limbs
      venous compression in preventing the occurrence of maternal hypotension after
      neuraxial anesthesia has already been demonstrated, but only in the context of
      scheduled cesarean section. We assessed the preventive effect of medical lower
      limbs venous compression on the incidence of maternal hypotension after epidural
      analgesia during spontaneous term labor. STUDY DESIGN: This before/after, single
      center study in a university hospital included 93 women in spontaneous labor at
      term who between 1 January and 31 March 2015 with epidural analgesia plus lower
      limbs compression and 202 women in spontaneous labor at term who delivered
      between 1 and 31 December 2014 with epidural analgesia without lower limbs
      compression (control group). The main outcome was maternal hypotension (systolic
      blood pressure <90mmHg and/or delta >20%) in the 15min after epidural analgesia.
      RESULTS: In the lower limbs compression group the incidence of hypotension 15min
      after epidural analgesia was significantly lower than in the control group (3.23%
      versus 23.3%, adjusted odds ratio=0.1 [0.03; 0.35]). The incidence of fetal heart
      rate abnormalities was unsignificantly lower in the lower limbs compression group
      than in the control group (10.7% versus 16.34%, p=0.22). CONCLUSION: The results
      suggest that medical lower limbs compression (20-36mmHg) in women in spontaneous
      labor at term, could significantly reduce the incidence of maternal hypotension
      following epidural analgesia. A prospective, randomized, open trial would allow
      confirmation of these preliminary results.

PMID- 29073509
TI  - Rhythms of the body, rhythms of the brain: Respiration, neural oscillations, and
      embodied cognition.
AB  - In spite of its importance as a life-defining rhythmic movement and its constant
      rhythmic contraction and relaxation of the body, respiration has not received
      attention in Embodied Cognition (EC) literature. Our paper aims to show that (1)
      respiration exerts significant and unexpected influence on cognitive processes,
      and (2) it does so by modulating neural synchronization that underlies specific
      cognitive processes. Then, (3) we suggest that the particular example of
      respiration may function as a model for a general mechanism through which the
      body influences cognitive functioning. Finally, (4) we work out the implications
      for EC, draw a parallel to the role of gesture, and argue that respiration
      sometimes plays a double, pragmatic and epistemic, role, which reduces the
      cognitive load. In such cases, consistent with EC, the overall cognitive activity
      includes a loop-like interaction between neural and non-neural elements.

PMID- 29073510
TI  - Haiku to enhance student learning: Experiences from a pathophysiology classroom.

PMID- 29073511
TI  - Differences between peritoneal and pleural mesothelioma in Lombardy, Italy.
AB  - BACKGROUND: We examined characteristics of peritoneal (PEM) and pleural (PLM)
      mesothelioma in Lombardy, Italy. METHODS: From the Lombardy Mesothelioma Registry
      we selected PEM (N=300) and PLM (N=5011) cases diagnosed in 2000-2014. We
      investigated asbestos exposure and presence of asbestosis or pleural plaques.
      RESULTS: Incidence rates (per 1,000,000 person-years, world standardized) of PEM
      were 1.2 (men) and 0.9 (women), compared with 22.6 and 8.4 for PLM. Asbestosis
      (both genders) and pleural plaques (men) were more frequent among PEM cases.
      Occupational asbestos exposure was similar in PEM and PLM cases. We found higher
      proportions of PEMs employed in the asbestos cement production. CONCLUSION: The
      higher frequency of pleural plaques in PEM cases confirm the association between
      asbestos and peritoneal mesothelioma. The higher proportions of asbestosis and of
      past employment in the asbestos-cement sector among PEM cases suggest a possible
      role of high exposures to asbestos in the peritoneal mesothelioma genesis.

PMID- 29073512
TI  - The stories of nursing student repeaters: A narrative inquiry study.
AB  - This narrative inquiry study examined community college nursing student
      repeaters, who failed a required nursing course and then went on to repeat the
      course. The purpose of this study was to learn about the experience of this group
      of students who are at high risk for attrition. While each participant had a
      unique story, common narratives emerged and were presented as storylines. Two
      storylines that are new to the literature were: Repeating is an Emotional
      Journey, and Ultimately Repeating was the Best Thing for Me. These findings
      suggest that there is a need for additional support for this population.

PMID- 29073513
TI  - The socially evaluated handgrip test: Introduction of a novel, time-efficient
      stress protocol.
AB  - Most widely-used stress-induction procedures (such as the TSST and the Cold
      Pressor Test) require considerable effort and overhead in terms of preparation,
      logistics, and staff recruitment. Moreover, while known to reliably induce HPA
      axis activation, especially when combined with social self-threat, most
      conventional laboratory stressors cannot be flexibly adapted to elicit either a
      mainly autonomic or an additional endocrine stress response. Being a promising
      alternative approach, a new version of the isometric handgrip test enriched by a
      social-evaluative component was evaluated in the present study. On two
      consecutive sessions, forty participants (20 women) performed a handgrip task at
      both 45% (stress) and 10% (control) of maximum voluntary isometric contraction
      lasting for 3min. During the stress test, continuous visual feedback on
      performance was given. Participants in the social-evaluative condition (50%) were
      observed and evaluated by a previously unknown person of the opposite sex,
      whereas in the standard condition feedback was provided via a computer monitor.
      Cardiovascular measures (heart rate, blood pressure) as well as additional
      indices of autonomic reactivity (skin conductance, heart-rate variability) were
      registered before, during, and after stress induction. Moreover, changes in
      salivary cortisol and in subjective well-being were assessed. Relative to
      control, significant increases in cardiovascular and sympathetic activity were
      found, irrespective of experimental group. Importantly, however, additional
      social evaluation resulted in elevated cortisol levels. Furthermore, evidence for
      reduced vagal tone during sustained socially evaluated handgrip emerged. In
      conclusion, the socially evaluated handgrip test represents a versatile, time
      efficient method to induce stress in small laboratory settings.

PMID- 29073514
TI  - Propellant's differentiation using FTIR-photoacoustic detection for forensic
      studies of improvised explosive devices.
AB  - The use of propellant for making improvised explosive devices (IED) is an
      incipient criminal practice. Propellant can be used as initiator in explosive
      mixtures along with other components such as coal, ammonium nitrate, sulfur, etc.
      The identification of the propellant's brand used in homemade explosives can
      provide additional forensic information of this evidence. In this work, four of
      the most common propellant brands were characterized by Fourier-transform
      infrared photoacoustic spectroscopy (FTIR-PAS) which is a non-destructive micro
      analytical technique. Spectra shows characteristic signals of typical compounds
      in the propellants, such as nitrocellulose, nitroglycerin, guanidine,
      diphenylamine, etc. The differentiation of propellant components was achieved by
      using FTIR-PAS combined with chemometric methods of classification. Principal
      component analysis (PCA) and soft independent modelling of class analogy (SIMCA)
      were used to achieve an effective differentiation and classification (100%) of
      propellant brands. Furthermore, propellant brand differentiation was also
      assessed using partial least squares discriminant analyses (PLS-DA) by leave one
      out cross (~97%) and external (~100%) validation method. Our results show the
      ability of FTIR-PAS combined with chemometric analysis to identify and
      differentiate propellant brands in different explosive formulations of IED.

PMID- 29073515
TI  - High risk of misinterpreting hair analysis results for children tested for
      methadone.
AB  - The major problem after testing the hair of a child for drugs is the
      interpretation of the findings. In 2016, the laboratory received several hair
      specimens with the request to verify if there was any evidence of previous
      methadone exposure by the donor of the sample. Case 1 was a child admitted to the
      Emergency Unit for intense sedation and breathing difficulties. Cases 2-4
      involved children found dead at home. In all cases, methadone and EDDP, its
      metabolite, were found in blood. After decontamination, the hair was analysed
      with LC-MS/MS for methadone and EDDP. The LOQ for both drugs was 10pg/mg.
      Concentrations were in the range 60-1590 and <10-220pg/mg for methadone and EDDP,
      respectively. In all of the cases, segmental analysis revealed approximately the
      same amount of drug along the hair lock. As a consequence, contamination was
      considered as an issue and interpretation of the results was a challenge that
      deserves particular attention. It must be considered that the amount of hair from
      children, available for analysis, can be low, particularly when several drugs
      have to be tested. This has consequences on the limit of quantitation and the
      identification of the metabolite(s). It must be also noted that hair from
      children is finer and more porous in comparison with adult (risk of higher
      contamination by sweat versus adults). It is very difficult to put any window of
      detection when testing for drugs in young children as hair growing is
      asynchronous. It is even more complicated as it has been demonstrated that drugs
      can be incorporated during pregnancy in the hair of the foetus, which will
      contribute to the positive findings after delivery. Several weeks or months after
      delivery, identification of a drug in hair can indicate: 1, in-utero exposure, or
      2, exposure after delivery, or 3, a mix of both situations. Whereas the detection
      of drugs in a child's hair unambiguously shows drug handling in the environment
      of the child, it is difficult to distinguish between systemic incorporation into
      hair after ingestion or inhalation and external deposition into hair from smoke,
      dust, or contaminated surfaces. However, the interpretation of hair results with
      respect to systemic or only external exposure is particularly important in case
      of children for a realistic assessment of the toxic health risk. Practising
      scientists have the responsibility to inform the child protection authorities,
      courts, etc about these limitations.

PMID- 29073516
TI  - Prefrontal cortex activation during a dual task in patients with stroke.
AB  - Dual tasks destabilize task performance as they involve competing demands for
      cognitive and physical resources. Several studies have reported that dual-task
      walking activates the prefrontal cortex (PFC), and recent studies have indicated
      a relationship between PFC and dual-task deterioration in healthy subjects.
      However, PFC activity during dual-task walking in stroke patients remains
      unclear. We investigated the association between PFC activity and dual-task
      interference on physical and cognitive performance in stroke patients. This study
      included 14 stroke patients and 14 healthy subjects who performed a calculation
      task while walking at a comfortable pace on the floor. PFC activity was assessed
      using wearable near-infrared spectroscopy. The calculation task and trunk linear
      accelerations were evaluated as measures of cognitive and physical performance.
      The dual-task deterioration on both physical and cognitive performance of stroke
      patients was significantly higher than in healthy subjects. PFC activation during
      dual-task walking was significantly lower in stroke patients. Although right PFC
      activation was negatively correlated with dual-task deterioration on physical
      performance in stroke patients, left PFC activation was negatively correlated
      with the dual-task cost on cognitive performance in healthy subjects. Thus,
      during dual-task walking, PFC activation might prioritize physical demands in
      stroke patients, but might prioritize cognitive demands in healthy subjects.

PMID- 29073517
TI  - Quantitative detection of exosomal microRNA extracted from human blood based on
      surface-enhanced Raman scattering.
AB  - Since the nature of the exosomal lipid bilayer can allow miRNAs to be protected
      from degradation by cellular RNAses in body fluids, exosomal microRNA (miRNA) has
      become an ideal source of non-invasive biomarkers for the early diagnosis and
      prognosis. In this paper, a new surface-enhanced Raman scattering (SERS) analysis
      strategy combining stable SERS reporter element and duplex-specific nuclease
      (DSN)-assisted signal amplification for quantitative detection of exosomal miRNA
      extracted from human blood is proposed. Firstly, we prepared SERS signal reporter
      of Au@R6G@AgAu nanoparticles (R6G attachment on the gold nanoparticles, then
      encapsulated in AgAu alloy shell nanoparticles named as ARANPs) with an inter
      small nanogap to generate stable SERS signal. Then, ARANPs and separating
      substrate of silicon microbead (SiMB) were then covalently attached to the 3'-
      and 5'- end of capture probe (CP) targeting exosomal miRNA. Upon target miRNA
      binding, DNA in heteroduplexes could be specifically cleaved by DSN and resulted
      in the release of ARANPs from the surface of SiMB. Meanwhile, target miRNA
      remained intact and subsequently involved in the next round of target-recycling
      amplification. The combination of stable SERS intensity and signal amplification
      significantly improved the sensitivity of the sensing systems, resulting in
      detection limits of 5 fM. More importantly, this method also could be used for
      the detection of exosomal miRNAs extracted from the blood collected from patients
      of recurrence in non-small-cell lung cancer (NSCLC), with a detection of 5.0MUL
      of sample volume, which has potential for point-of-care testing (POCT) in
      clinical analysis.

PMID- 29073518
TI  - An aptasensor based on heparin-mimicking hyperbranched polyester with anti
      biofouling interface for sensitive thrombin detection.
AB  - In this paper, novel heparin-mimicking hyperbranched polyester nanoparticles
      (HBPE-SO3 NPs) with abundant of sulfonated acid functional groups were
      synthesized, and their antithrombogenicities were further evaluated. Further, a
      label-free electrochemical aptamer biosensor (aptasensor) based on HBPE-SO3 NPs
      modified electrode was developed for thrombin (TB) detection in whole blood.
      Meanwhile, the anti-biofouling properties of different modified electrodes were
      studied by whole blood and platelet adhesion test, hemolysis assay and
      morphological changes of red blood cells in vitro. Besides, the thrombin-binding
      aptamer was selected as receptor for the proposed aptasensor, which has excellent
      binding affinity and selectivity for TB. When binding to TB, the electron
      transfer taking place at the modified electrode interface was inhibited that can
      attribute to the stereo-hindrance effect, resulting in the decreased current
      response. This aptasensor showed excellent electrochemical properties with a wide
      detection range and a low detection limit of 0.031pM (S/N = 3), and provided high
      selectivity, long-term stability and good reproducibility. Finally, the
      sensitively detection of TB in whole blood samples directly was achieved by this
      aptasensor we proposed, which suggested its great potential for TB detection in
      the clinic.

PMID- 29073519
TI  - Re-usable electrochemical glucose sensors integrated into a smartphone platform.
AB  - This article demonstrates a new smartphone-based reusable glucose meter. The
      glucose meter includes a custom-built smartphone case that houses a permanent
      bare sensor strip, a stylus that is loaded with enzyme-carbon composite pellets,
      and sensor instrumentation circuits. A custom-designed Android-based software
      application was developed to enable easy and clear display of measured glucose
      concentration. A typical test involves the user loading the software, using the
      stylus to dispense an enzymatic pellet on top of the bare sensor strip affixed to
      the case, and then introducing the sample. The electronic module then acquires
      and wirelessly transmits the data to the application software to be displayed on
      the screen. The deployed pellet is then discarded to regain the fresh bare sensor
      surface. Such a unique working principle allows the system to overcome challenges
      faced by previously reported reusable sensors, such as enzyme degradation,
      leaching, and hysteresis effects. Studies reveal that the enzyme loaded in the
      pellets are stable for up to 8 months at ambient conditions, and generate
      reproducible sensor signals. The work illustrates the significance of the pellet
      based sensing system towards realizing a reusable, point-of-care sensor that
      snugly fits around a smartphone and which does not face issues usually common to
      reusable sensors. The versatility of this system allows it to be easily modified
      to detect other analytes for application in a wide range of healthcare,
      environmental and defense domains.

PMID- 29073520
TI  - Label-free biosensors in the field of stem cell biology.
AB  - A great body of evidence unveiled the existence of different stem cell types in
      various tissues with efficient capability for self-renewal and differentiation.
      Characterization and enumeration of a specific stem cell population seem
      difficult because these cells consist of a small percentage of cells within
      different milieu. As such, due to lack of accuracy provided by convenient
      methods, biosensing techniques are at the center of attention to improve stem
      cells characterization with high rate of sensitivity and specificity. In line
      with this statement, bio-sensing, as a sensitive analytical method, opens novel
      avenues in biological aspects. Physicochemical signals produced by the
      interaction of analyte-ligands could be applicable for a wide range of scientific
      fields such as chemical, biochemical, pharmaceutical and immunological purposes.
      Noninvasive and label free monitoring methods without need to stain, fix, lyse,
      or fluorescent-tags are desirable in basic stem cell technology and therapeutic
      applications of cells. We, here, highlighted basic concepts and terms associated
      with label free biosensor technology for measuring cell entity, evaluating cell
      surface marker, and peculiarly in the field of stem cell biology. Furthermore,
      different aspects and methodologies concerning with bio-sensing techniques,
      including photonic-based detection systems like Surface Plasmon Resonance (SPR)
      assays, Impedance-based method, Quartz Crystal Microbalance (QCM) and paper based
      detection of lateral flow biosensor (LFB) were discussed.

PMID- 29073521
TI  - Surpassing the current limitations of high purity H2 production in microbial
      electrolysis cell (MECs): Strategies for inhibiting growth of methanogens.
AB  - Microbial electrolysis cells (MECs) are perceived as a potential and promising
      innovative biotechnological tool that can convert carbon-rich waste biomass or
      wastewater into hydrogen (H2) or other value-added chemicals. Undesired methane
      (CH4) producing H2 sinks, including methanogens, is a serious challenge faced by
      MECs to achieve high-rate H2 production. Methanogens can consume H2 to produce
      CH4 in MECs, which has led to a drop of H2 production efficiency, H2 production
      rate (HPR) and also a low percentage of H2 in the produced biogas. Organized
      inference related to the interactions of microbes and potential processes has
      assisted in understanding approaches and concepts for inhibiting the growth of
      methanogens and profitable scale up design. Thus, here in we review the current
      developments and also the improvements constituted for the reduction of microbial
      H2 losses to methanogens. Firstly, the greatest challenge in achieving practical
      applications of MECs; undesirable microorganisms (methanogens) growth and various
      studied techniques for eliminating and reducing methanogens activities in MECs
      were discussed. Additionally, this extensive review also considers prospects for
      stimulating future research that could help to achieve more information and would
      provide the focus and path towards MECs as well as their possibilities for
      simultaneously generating H2 and waste remediation.

PMID- 29073522
TI  - Maternal psychological distress after preterm birth: Disruptive or adaptive?
AB  - BACKGROUND: Maternal postpartum distress is often construed as a marker of
      vulnerability to poor parenting. Less is known, however, about the impact of
      postpartum distress on parenting an infant born prematurely. The present study
      investigated whether high distress levels, which are particularly prevalent in
      mothers of preterm born infants, necessarily affect a mother's quality of
      parenting. METHOD: Latent Class Analysis was used to group mothers (N=197) of
      term, moderately, and very preterm born infants, based on their levels of
      distress (depression, anxiety, and PTSD symptoms) at one month postpartum, and
      their quality of parenting at one and six months postpartum. Parenting quality
      was assessed on the basis of maternal interactive behaviors (sensitivity,
      intrusiveness, and withdrawal) using observations, and maternal attachment
      representations (balanced, disengaged, or distorted) using interviews. RESULTS: A
      5-Class model yielded the best fit to the data. The first Class (47%) of mothers
      was characterized by low distress levels and high-quality parenting, the second
      Class (20%) by low distress levels and low-quality parenting, the third Class
      (22%) by high distress levels and medium-quality parenting, the fourth Class (9%)
      by high distress levels and high-quality parenting, and finally the fifth Class
      (2%) by extremely high levels of distress and low-quality parenting. CONCLUSIONS:
      While heightened distress levels seem inherent to preterm birth, there appears to
      be substantial heterogeneity in mothers' emotional responsivity. This study
      indicates that relatively high levels of distress after preterm birth do not
      necessarily place these mothers at increased risk with regard to poor parenting.
      Conversely, low distress levels do not necessarily indicate good-quality
      parenting. The results of the present study prompt a reconsideration of the
      association between postpartum distress and parenting quality, and challenge the
      notion that high levels of maternal distress always result in low-quality
      parenting practices.

PMID- 29073523
TI  - Molecular oxidative stress markers in olive ridley turtles (Lepidochelys
      olivacea) and their relation to metal concentrations in wild populations.
AB  - Due to their longevity and extensive migration areas, marine turtles are able to
      accumulate diverse contaminants over many years and as a consequence they
      represent an interesting bioindicator species for marine ecosystem pollution.
      Metals provoke toxicological effects in many aquatic animal species, but marine
      turtles have been under-investigated in this area. Thus, we have determined the
      presence of certain inorganic elements (As, Cd, Cu, Ni, Pb, Se and Zn) in olive
      ridley turtles (Lepidochelys olivacea) and related them to metallothionein (MT),
      superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR)
      transcription and/or enzymatic activities. Gene expression of sod, cat and gr was
      found to be higher in blood than liver or kidney but most of the significant
      relationships were found in liver, not only for gene expression but also for
      enzyme activities. This must be related to the role the liver has as the first
      filter organ. Several positive relationships of sod, cat and gr gene expression
      in the different tissues were found in this population, as well as very high Cd
      concentrations. This could mean that these turtles are adapting to the metals
      production of ROS and damage through a high transcription of these antioxidants.
      Multiple positive relationships with GR seem to be part of its compensatory
      effect due to the decrease of SOD production against the high and chronic
      exposure to certain xenobiotics. CAT, on the other hand, seems not to be used
      much, and glutathione detoxification of H2O2 may be more important in this
      species. Finally, despite the very high Cd concentrations found in this
      population, no significant relationship was found in any tissue with
      metallothionein gene expression. These results, along with very high Cd
      concentrations and a negative relationship with Cu, lead us to consider some kind
      of disruption in mt gene expression in these turtles.

PMID- 29073525
TI  - Indoor particulate pollution in fitness centres with emphasis on ultrafine
      particles.
AB  - Fitness centres (FC) represent a unique indoor microenvironment. Exercising on
      regular basis provides countless health benefits and improves overall well-being,
      but if these facilities have poor indoor air quality, the respective exercisers
      might be subjected to some adverse risks. Considering the limited existent data,
      this work aimed to evaluate particulate pollution (PM10, PM2.5, and ultrafine
      particles - UFP) in indoor air of FC and to estimate the respective risks for
      occupants (both staff and exercising subjects). Sampling was conducted during 40
      consecutive days of May-June 2014 in general fitness areas, studios and
      classrooms (for group activities) of four different fitness centres (FC1-FC4)
      situated within Oporto metropolitan area, Portugal. The results showed that
      across the four FC, PM10 ranged between 5 and 1080 MUg m-3 with median
      concentrations (15-43 MUg m-3) fulfilling the limit (50 MUg m-3) of Portuguese
      legislation in all FC. PM2.5 (medians 5-37 MUg m-3; range 5-777 MUg m-3) exceeded
      thresholds of 25 MUg m-3 at some FC, indicating potential risks for the
      respective occupants; naturally ventilated FC exhibited significantly higher PM
      ranges (p < 0.05). Similarly, UFPs (range 0.5-88.6 * 103 # cm-3) median
      concentrations were higher (2-3 times) at FC without controlled ventilation
      systems. UFP were approximately twice higher (p < 0.05) during the occupied
      periods (mean of 9.7 * 103vs. 4.8 * 103 # cm-3) with larger temporal variations
      of UFP levels observed in general fitness areas than in classrooms and studios.
      Cardio activities (conducted in studios and classrooms) led to approximately
      twice the UFPs intakes than other types of exercising. These results indicate
      that even short-term physical activity (or more specifically its intensity) might
      strongly influence the daily inhalation dose. Finally, women exhibited 1.2 times
      higher UFPs intake than men thus suggesting the need for future gender-specific
      studies assessing UFP exposure.

PMID- 29073524
TI  - Trends in bromide wet deposition concentrations in the contiguous United States,
      2001-2016.
AB  - Bromide (Br-) and other solute concentration data from wet deposition samples
      collected and analyzed by the National Atmospheric Deposition Program (NADP) from
      2001 to 2016, were statistically analyzed for trends both geographically and
      temporally by precipitation type. Analysis was limited to NADP sites in the
      contiguous 48 United States. The Br- concentrations for this time period had a
      high number of values censored at the detection limits with greater than 86
      percent of sample concentrations below analytical detection. Bromide was more
      frequently detected at NADP sites in coastal regions. Analysis using specialized
      statistical techniques for censored data revealed that Br- concentrations varied
      by precipitation type with higher concentrations usually observed in liquid
      versus precipitation containing snow. Negative temporal trends in Br- wet
      deposition concentrations were observed at a majority of NADP sites;
      approximately 25 percent of these trend values were statistically significant at
      less than 0.05 to 0.10 significance levels. Potential causes for the negative
      trends were explored, including annual and seasonal changes in precipitation
      depth, reduced emissions of methyl bromide (CH3Br) from coastal wetlands, and
      declining industrial use of bromine compounds. The results indicate that Br- in
      non-coastal wet-deposition comes mainly from long-range transport, not local
      sources. Correlations between Br-, chloride, and nitrate concentrations also were
      evaluated.

PMID- 29073526
TI  - Monitoring the antioxidant effects of catechin using single-walled carbon
      nanotubes: Comparative analysis by near-infrared absorption and near-infrared
      photoluminescence.
AB  - We measured the optical responses of single-walled carbon nanotubes (SWNTs) after
      adding Japanese green tea or catechin. SWNTs were covered with DNA in aqueous
      solution, and tea or catechin solution was added to the DNA-SWNT suspension. The
      antioxidant effects of tea and catechin were detected as changes in the near
      infrared (NIR) absorption (ABS) and NIR-photoluminescence (PL) spectra of the
      SWNTs. Commercial Japanese tea, diluted 100 times and containing 15MUg/mL
      catechin, was sufficient for recovering NIR-ABS and NIR-PL spectra when the DNA
      SWNT suspension was pre-treated with 0.03% hydrogen peroxide(H2O2). Similar
      results were obtained with 15MUg/mL of pure catechin solution. SWNTs with
      specific chirality were sensitive to the NIR-ABS and NIR-PL changes. The (10,
      5)/(8, 7) and (9, 4) SWNTs showed the highest recovery in NIR-ABS and NIR-PL,
      respectively. NIR-PL recovery was higher than that of NIR-ABS for (10, 5)/(8, 7)
      and (9, 4). Spectral changes could be monitored thoroughly at pH 8.0, contrary to
      pH 6.0 and 7.3. However, the most dynamic recovery of NIR-ABS and NIR-PL was
      observed at pH 6.0. Furthermore, time-lapse measurements revealed that recovery
      was faster with tea or catechin addition than H2O2-induced oxidation.

PMID- 29073527
TI  - EPR, TEM and cell viability study of asbestiform zeolite fibers in cell media.
AB  - Human monocyte U937 cell line was used as a model to verify the toxicity of
      erionite and offretite asbestiform zeolite fibers. As a presumed non-toxic
      reference, a fibrous scolecite zeolite was also used. To analyze the process of
      fiber ingestion into cells and the cells-fibers interactions, a spin-probe
      electron paramagnetic resonance (EPR) analysis was performed supported by
      transmission electron microscopy (TEM) and cell viability measurements as a
      function of the incubation time. Erionite fibers were fast internalized in the
      membrane mainly as aggregates with radical-solution drops trapped inside, and
      were found in the cytosol and at the nucleus. In 24h, first erionite fibers rich
      in sodium and potassium, and then calcium-rich erionite fibers, induced cell
      necrosis. The offretite fibers formed rounding electron-dense filaments which
      transformed in curved filaments, initially perturbing the cell structure and
      interacting at the external surface more than erionite fibers. Such interactions
      probably diminished the toxic effect of offretite on cells. Interestingly, the
      presumed non-toxic scolecite fibers were partially internalized, inducing
      formation of swollen mitochondria and squared cells. Overall, the toxic effect of
      the fibrous zeolites was related to fiber morphology, chemical distribution of
      sites, structural variations and formation of aggregates.

PMID- 29073528
TI  - Microglia: origins, homeostasis, and roles in myelin repair.
AB  - Microglia are the resident macrophages of the central nervous system (CNS),
      implicated in developmental processes, homeostasis, and responses to injury.
      Derived from the yolk sac during development, microglia self-renew, self-regulate
      their numbers during homeostatic conditions, and show a robust proliferative
      capacity even in adulthood. Together with monocyte-derived macrophages (MDM),
      microglia coordinate the regeneration of CNS myelin around axons, termed
      remyelination. Gene expression analyses and experimental modelling have
      identified pro-remyelination roles for microglia/MDM in clearance of myelin
      debris, secretion of growth factors, and remodelling of the extracellular matrix.
      Further investigations into the molecular mechanisms controlling these
      regenerative functions will reveal novel therapeutic strategies to enhance
      remyelination, by harnessing the beneficial effects of the innate immune response
      to injury.

PMID- 29073530
TI  - Age-related outcomes associated with personality pathology in later life.
AB  - Methodological advances enable the latest research on personality pathology in
      later life to turn toward understanding the role personality pathology plays in
      age-related outcomes. Despite indications that some features of personality
      disorders fade in later life, a prevalence rate of approximately 10 percent has
      been established for adults aged 50 or older. Personality disorder features have
      been linked to suicidal ideation, poorer physical health, and cognitive decline
      in later life. Given these associations, the literature on treatment of
      personality disorders in this age group is surprisingly scant. Future research
      needs to address this lack in order to provide guidelines for the use of the DSM
      5 Alternative Model for Personality Disorders with older adults.

PMID- 29073531
TI  - Automatic initialization and quality control of large-scale cardiac MRI
      segmentations.
AB  - Continuous advances in imaging technologies enable ever more comprehensive
      phenotyping of human anatomy and physiology. Concomitant reduction of imaging
      costs has resulted in widespread use of imaging in large clinical trials and
      population imaging studies. Magnetic Resonance Imaging (MRI), in particular,
      offers one-stop-shop multidimensional biomarkers of cardiovascular physiology and
      pathology. A wide range of analysis methods offer sophisticated cardiac image
      assessment and quantification for clinical and research studies. However, most
      methods have only been evaluated on relatively small databases often not
      accessible for open and fair benchmarking. Consequently, published performance
      indices are not directly comparable across studies and their translation and
      scalability to large clinical trials or population imaging cohorts is uncertain.
      Most existing techniques still rely on considerable manual intervention for the
      initialization and quality control of the segmentation process, becoming
      prohibitive when dealing with thousands of images. The contributions of this
      paper are three-fold. First, we propose a fully automatic method for initializing
      cardiac MRI segmentation, by using image features and random forests regression
      to predict an initial position of the heart and key anatomical landmarks in an
      MRI volume. In processing a full imaging database, the technique predicts the
      optimal corrective displacements and positions in relation to the initial rough
      intersections of the long and short axis images. Second, we introduce for the
      first time a quality control measure capable of identifying incorrect cardiac
      segmentations with no visual assessment. The method uses statistical, pattern and
      fractal descriptors in a random forest classifier to detect failures to be
      corrected or removed from subsequent statistical analysis. Finally, we validate
      these new techniques within a full pipeline for cardiac segmentation applicable
      to large-scale cardiac MRI databases. The results obtained based on over 1200
      cases from the Cardiac Atlas Project show the promise of fully automatic
      initialization and quality control for population studies.

PMID- 29073529
TI  - Oligodendroglia-lineage cells in brain plasticity, homeostasis and psychiatric
      disorders.
AB  - Adult oligodendrocyte progenitor cells are uniformly distributed in both gray and
      white matter, displaying robust proliferative and migratory potential during
      health and disease. Recently, developments in new experimental approaches have
      brought about several novel insights about NG2-glia and myelinating
      oligodendrocytes, indicating a diverse toolkit of functions in experience
      dependent myelination and homeostasis in the adult CNS. In this review, we
      summarize some of the topical studies that highlight newly emerging findings
      implicating oligodendroglia-lineage cells in brain plasticity, homeostasis and
      pathophysiology of neuropsychiatric disorders.

PMID- 29073532
TI  - Sexual dimorphism and regional variation in human frontal bone inclination
      measured via digital 3D models.
AB  - The frontal bone is one of the most sexually dimorphic elements of the human
      skull, due to features such as the glabella, frontal eminences, and frontal
      inclination. While glabella is frequently evaluated in procedures to estimate sex
      in unknown human skeletal remains, frontal inclination has received less
      attention. In this study we present a straightforward, quick, and reproducible
      method for measuring frontal inclination angles from glabella and supraglabella.
      Using a sample of 413 human crania from four different populations (U.S. Whites,
      U.S. Blacks, Portuguese, and Chinese), we test the usefulness of the inclination
      angles for sex estimation and compare their performance to traditional methods of
      frontal inclination assessment. Accuracy rates in the range 75-81% were achieved
      for the U.S. White, U.S. Black, and Portuguese groups. For Chinese the overall
      accuracy was lower, i.e. 66%. Although some regional variation was observed, a
      cut-off value of 78.2 degrees  for glabellar inclination angles separates female
      and male crania from all studied populations with good accuracy. As inclination
      angles measured from glabella captures two sexually dimorphic features (i.e.
      glabellar prominence and frontal inclination) in a single measure, the observed
      clear male/female difference is not unexpected. Being continuous variables,
      inclination angles are suitable for use in statistical methods for sex
      estimations.

PMID- 29073533
TI  - Planned and unplanned complex suicides: Casuistry of the Institute of Legal
      Medicine of Parma (Italy).
AB  - Complex suicide is performed using more harmful methods, simultaneously or
      consecutively. In these cases, the distinction between suicide and homicide
      represents a challenge for forensic pathologists. In literature, complex suicide
      is divided in two subgroups: "planned complex suicide" or "unplanned complex
      suicide" depending from forensic features and often related to psychiatric
      variables. Aim of this study was to show the casuistry of complex suicide in
      Parma's Forensic service analyzing, for each case, the forensic medical problems
      (type and site of lesions on the body), and the supplementary data [Police's
      inspection report, toxicological analysis and psychiatric anamnesis (when
      available)], trying, through a multidisciplinary approach, to determine a
      possible correlation between the victim's mood and suicide's method chosen,
      whether planned or unplanned. Our results showed the importance of all the
      elements collected on the crime scene to distinguish suicide from homicide, and
      the correlation between bipolar disorder, borderline personality disorder and
      schizophrenia with unplanned complex suicide (because of the impulsiveness), and
      major depression disorder and anxiety disorder with planned complex suicide.
      Being able to understand the causes behind this extreme gesture may become
      important not only for forensic pathologists and judicial authority, but also,
      and above all, for the family as well.

PMID- 29073534
TI  - 3-month prognostic impact of severe acute renal failure under veno-venous ECMO
      support: Importance of time of onset.
AB  - PURPOSE: Veno-venous ECMO is increasingly used for the management of refractory
      ARDS. In this context, acute kidney injury (AKI) is a major and frequent
      complication, often associated with poor outcome. We aimed to identify
      characteristics associated with severe renal failure (Kidney Disease Improving
      Global Outcome (KDIGO) 3) and its impact on 3-month outcome. METHODS: Between May
      2009 and April 2016, 60 adult patients requiring VV-ECMO in our University
      Hospital were prospectively included. RESULTS: AKI occurrence was frequent (75%;
      n=45), 51% of patients (n=31) developed KDIGO 3 - predominantly prior to ECMO
      insertion - and renal replacement therapy was required in 43% (n=26) of cases.
      KDIGO 3 was associated with a lower mechanical ventilation weaning rate (24% vs
      68% for patients with no AKI or other stages of AKI; p<0.001) and a higher 90-day
      mortality rate (72% vs 32%, p=0.002). Multivariate logistic regression suggested
      that KDIGO 3 occurrence prior to ECMO insertion, as well as PaCO2>57mmHg and
      mSOFA>12 were independent risks factors for 90-day mortality. CONCLUSION: KDIGO 3
      AKI occurrence is correlated with the severity of patients' clinical condition
      prior to ECMO insertion and is negatively associated with 90-day survival.

PMID- 29073535
TI  - Low tidal volume ventilation use remains low in patients with acute respiratory
      distress syndrome at a single center.
AB  - PURPOSE: Low tidal volume ventilation (LTVV) reduces mortality in acute
      respiratory distress syndrome (ARDS) patients. Understanding local barriers to
      LTVV use at a former ARDS Network hospital may provide new insight to improve
      LTVV implementation. METHODS: A cohort of 214 randomly selected adults met the
      Berlin definition of ARDS at Harborview Medical Center between 2008 and 2012. The
      primary outcome was the receipt of LTVV (tidal volume of <=6.5mL/kg predicted
      body weight) within 48h of ARDS onset. We constructed a multivariable logistic
      regression model to identify factors associated with the outcome. RESULTS: Only
      27% of patients received tidal volumes of <=6.5mL/kg PBW within 48h of ARDS
      onset. Increasing plateau pressure (OR 1.11; 95% CI 1.03 to 1.19; p-value<0.01)
      was positively associated with LTVV use while increasing PaO2:FIO2 ratio was
      negatively associated (OR 0.75; 95% CI 0.57 to 0.98; p-value 0.03). Physicians
      documented an ARDS diagnosis in only 21% of the cohort. Neither patient height
      nor gender was associated with LTVV use. CONCLUSIONS: Most ARDS patients did not
      receive LTVV despite implementation of a protocol. ARDS was also recognized in a
      minority of patients, suggesting an opportunity for improvement of care.

PMID- 29073536
TI  - Intensive care unit drug costs in the context of total hospital drug expenditures
      with suggestions for targeted cost containment efforts.
AB  - PURPOSE: To assess costs of intensive care unit (ICU) related pharmacotherapy
      relative to hospital drug expenditures, and to identify potential targets for
      cost-effectiveness investigations. We offer the unique advantage of comparing ICU
      drug costs with previously published data a decade earlier to describe changes
      over time. MATERIALS AND METHODS: Financial transactions for all ICU patients
      during fiscal years (FY) 2009-2012 were retrieved from the hospital's data
      repository. ICU drug costs were evaluated for each FY. ICU departments' charges
      were also retrieved and calculated as percentages of total ICU charges. RESULTS:
      Albumin, prismasate (dialysate), voriconazole, factor VII and alteplase denoted
      the highest percentages of ICU drug costs. ICU drug costs contributed to an
      average of 31% (SD 1.0%) of the hospital's total drug costs. ICU drug costs per
      patient day increased by 5.8% yearly versus 7.8% yearly for non-ICU drugs. This
      rate was higher for ICU drugs costs at 12% a decade previous. Pharmacy charges
      contributed to 17.7% of the total ICU charges. CONCLUSIONS: Growth rates of costs
      per year have declined but still drug expenditures in the ICU are consistently a
      significant driver in this resource intensive environment with a high impact on
      hospital drug expenditures.

PMID- 29073537
TI  - Diagnostic accuracy of delirium assessment methods in critical care patients.
AB  - PURPOSE: Delirium is a disorder of decreased ability to focus, sustain or shift
      attention, change in cognition and or perception. The main objective was to
      evaluate the diagnostic accuracy of Confusion Assessment Method for the ICU (CAM
      ICU) and Intensive Care Delirium Screening Checklist (ICDSC) among the nursing
      and medical staff in a multidisciplinary ICU. METHODS AND MATERIAL: Three hundred
      ten verbally communicating and non-communicating patients (mean age in years
      47.9, standard deviation [SD] 14.5, mean Acute Physiology and Chronic Health
      Evaluation II score 13.8, SD 6.4) were assessed by a psychiatrist, nurse and
      intensivist for delirium. Inter-rater agreement was measured by Cohen's kappa
      coefficient. Sensitivity, specificity, predictive values, likelihood ratios and
      diagnostic odds ratio (DOR) were calculated. RESULTS: CAM-ICU showed higher
      sensitivity and DOR (84%, 86.1) compared to ICDSC (78%, 36.9). ICDSC had
      specificity and positive predictive value (94.5%, 92%) equal to that of CAM-ICU.
      For both the assessment methods (CAM-ICU and ICDSC), DORs for intensivists
      (120.5, 53.0) were relatively higher than nurses (67.0, 27.0). CONCLUSIONS: In
      our mixed ICU population, CAM-ICU remained more sensitive than ICDSC. Though
      sensitivity and DOR were higher for medical staff, other diagnostic parameters
      were similar for both medical and nursing staff.

PMID- 29073538
TI  - Effects of prolonged drought on stem non-structural carbohydrates content and
      post-drought hydraulic recovery in Laurus nobilis L.: The possible link between
      carbon starvation and hydraulic failure.
AB  - Drought-induced tree decline is a complex event, and recent hypotheses suggest
      that hydraulic failure and carbon starvation are co-responsible for this process.
      We tested the possible role of non-structural carbohydrates (NSC) content on post
      drought hydraulic recovery, to verify the hypothesis that embolism reversal
      represents a mechanistic link between carbon starvation and stem hydraulics.
      Measurements were performed in laurel plants subjected to similar water stress
      levels either over short or long term, to induce comparable embolism levels.
      Plants subjected to mild and prolonged water shortage (S) showed reduced growth,
      adjustment of turgor loss point driven by changes in both osmotic potential at
      full turgor and bulk modulus of elasticity, a lower content of soluble NSC and a
      higher content of starch with respect to control (C) plants. Moreover, S plants
      showed a lower ability to recover from xylem embolism than C plants, even after
      irrigation. Our data suggest that plant carbon status might indirectly influence
      plant performance during and after drought via effects on xylem hydraulic
      functioning, supporting the view of a possible mechanistic link between the two
      processes.

PMID- 29073539
TI  - ScDREB8, a novel A-5 type of DREB gene in the desert moss Syntrichia caninervis,
      confers salt tolerance to Arabidopsis.
AB  - Salinity is a major limitation factor for crop productivity worldwide. DREB
      transcription factors broadly participate in plant stress response and have been
      extensively identified in a wide variety of plants. In this study, we
      characterized and analyzed the function of a novel A-5 type DREB gene ScDREB8
      from the desiccation tolerant moss Syntrichia caninervis. Yeast one-hybrid
      experiment showed that ScDREB8 had no transactivation activity. Transient
      expression assay in onion epidermal cells revealed that ScDREB8 is distributed
      throughout the cell with no apparent specificity. Overexpression of ScDREB8
      significantly increased the germination rate of Arabidopsis under salt stress and
      improved the salt tolerance of Arabidopsis at the seedling stage by up-regulating
      the expression of downstream stress-related genes and improving ROS scavenging
      ability. ScDREB8 is a promising candidate gene for improving crop salt stress and
      will provide greater insight to the molecular mechanism of stress tolerance of A
      5 type DREB proteins.

PMID- 29073540
TI  - Uterine endometrial vascularization during ovarian follicular growth in llamas:
      The effect of estradiol plasma concentration.
AB  - The aim of this study was to evaluated changes in endometrial vascularization
      area (EVA) between the left and right uterine horn: a) during the ovarian
      follicular growth in intact llamas, and b) after exogenous estradiol
      administration of estradiol benzoate in ovariectomized (OVX) llamas. In
      experiment 1 follicle wave emergence was synchronized (n = 5 llamas) by follicle
      ablation (Day 0). Females were examined every other day from Day 1 to Day 27,
      using B mode ultrasonography to evaluate dominant follicle growth profile. Also,
      EVA was evaluated in each horn using Color-Power Doppler. Blood samples were
      taken every other day from Day 1 to Day 27 to measure estradiol (E2) plasma
      concentration by RIA. In experiment 2 OVX llamas (n = 4 llamas/group) were given
      a single im administration of: a) 1 mg of estradiol benzoate (EB) or b) 1 mL of
      saline. Females were subjected to ultrasound examinations every 48 h from Day -4
      until treatment (Day 0), every 12 h from Day 0 to Day 4, and again every 48 h
      from Day 5 to Day 11. Evaluation of EVA in both uterine horns was performed as
      described for experiment 1. Blood sampling for the measurement of E2 was carried
      out at the same time points indicated for the ultrasound examinations. Serial
      data were analyzed by one way ANOVA for repeated measures using the MIXED
      Procedure in SAS. Also, Pearson's correlation was used to determine the
      relationship between variables. In intact llamas there was an effect of day on
      the dominant follicle growing profile (P < 0.01) and estradiol plasma
      concentration (P < 0.05). Dominant follicle diameter positively correlated (r =
      0.4; P < 0.017) with estradiol plasma concentration. Also, EVA of right and left
      uterine horn did not differ (P = 0.89) during the evaluation period; however, it
      was affected by time (P < 0.05). In ovariectomized llamas estradiol concentration
      was significantly (P < 0.001) affected by treatment, time and their interaction.
      Accordingly, treatment with EB (P < 0.0001), time (P < 0.05) and their
      interaction (P < 0.01) affected EVA of both uterine horns; however, this variable
      did not differ between horns (P = 0.98). In conclusion, circulating
      concentrations of estradiol determined an increase in uterine vascularization,
      during the phase of follicular growth in intact llamas and after the exogenous
      administration of EB to ovariectomized females; however, no differential effect
      in endometrial vascularization area between right and left uterine horn was
      observed.

PMID- 29073541
TI  - Melatonin promotes sheep Leydig cell testosterone secretion in a co-culture with
      Sertoli cells.
AB  - Leydig cells synthesize and secrete testosterone, and are regulated by Sertoli
      cells. These two cell types may work together to regulate testicular androgen
      production. Studies have shown that Leydig cell androgen synthesis can be
      dramatically enhanced by Sertoli cells in the presence of melatonin, which can
      regulate the secretory function of Leydig and Sertoli cells. However, the
      molecular mechanism of melatonin-regulated Leydig cell androgen production via
      Sertoli cells remains unclear. Here, we found that 10-7 M melatonin increased
      testosterone production in co-cultured Leydig and Sertoli cells isolated from
      sheep. Melatonin increased the expression of stem cell factor and insulin-like
      growth factor-1 and decreased estrogen synthesis in Sertoli cells. Melatonin
      promoted insulin-like growth factor-1 and decreased estrogen content via the
      membrane melatonin receptor 1. It also enhanced stem cell factor expression via
      the retinoic acid receptor-related orphan receptor alpha. Addition of PD98059, a
      MEK inhibitor, to Sertoli cell culture demonstrated that the melatonin
      upregulation of insulin-like growth factor-1 and downregulation of estrogen may
      be through the MEK/extracellular signal-regulated kinase pathway. Together, these
      results suggest that melatonin may function through modulating melatonin receptor
      1-regulated insulin-like growth factor-1 expression, as well as melatonin
      receptor 1-induced suppression of estrogen synthesis to increase androgen
      production in co-cultured Leydig and Sertoli cells.

PMID- 29073542
TI  - Pregnancy diagnosis in cattle using pregnancy associated glycoprotein
      concentration in circulation at day 24 of gestation.
AB  - Cattle producers are limited to day 28-30 of gestation as the earliest time point
      for accurate pregnancy diagnosis due to the effectiveness of ultrasound and
      chemical based methods, including commercially available pregnancy associated
      glycoproteins (PAG) tests. The objective of the current studies were to determine
      if early gestation circulating PAG concentrations at day 24 could be used to
      diagnose pregnancy in dairy cattle undergoing embryo transfer. In vitro produced
      embryos were transferred into Holstein x Gir cows and heifers on day 7 following
      ovulation. Study 1 utilized only cows (n = 101) determined to be pregnant on day
      24 of gestation by progesterone concentration, as well as CL and PAG presence. In
      study 2, animals were not predetermined to be pregnant and both heifers (n = 111)
      and cows (n = 242) were used. In both studies, blood was collected at day 24 for
      PAG analysis as well as day 31. Final pregnancy confirmation occurred on day 60
      via transrectal ultrasonography. Serum PAG concentrations were quantified using
      an in house PAG ELISA. Following timed embryo transfer (TET) in study 1, of the
      101 cows diagnosed as pregnant on day 24, 80 cows were identified as still
      pregnant on day 31 of gestation (77%). Study 2 had a pregnancy rate at day 31 of
      33.7% of total embryos transferred. Mean circulating PAG concentration at day 24
      differed (P < 0.001) between animals diagnosed pregnant and non-pregnant at day
      31 in both studies (study 1, 2.964 +/- 0.262 ng/mL vs 0.946 +/- 0.168 ng/mL and
      study 2, 1.962 +/- 0.261 ng/mL vs 0.731 +/- 0.109 ng/mL). Concentration of PAG
      between pregnant and non-pregnant cows in study 1 and 2 was significant, however,
      pregnant heifers in study 2 (1.562 +/- 0.266 ng/mL) had concentration of PAGs
      that only had a tendency to differ compared to non-pregnant heifers (non
      pregnant, 0.799 +/- 0.290 ng/mL; P = 0.0669). Only animals that were pregnant at
      day 31 were analyzed in late embryo mortality analysis (heifers, n = 54; cows, n
      = 159), defined as pregnancy loss between day 31 and 60. Between day 31 and 60,
      39 (12 in study 1 and 28 in study 2) animals experienced late embryo mortality.
      Circulating concentrations of PAG were not significantly different (P > 0.05), in
      either study, at day 24 of gestation in animals that maintained pregnancy until
      day 60 compared to animals that lost pregnancy between day 31 and 60 (late embryo
      mortality, LEM). In summary, early gestation circulating PAG concentration may
      have application in diagnosing pregnancy at day 24 of gestation and more work is
      needed to determine the potential of early gestation PAGs in predicting embryo
      loss in dairy.

PMID- 29073543
TI  - A simple fluorescent probe for the fast sequential detection of copper and
      biothiols based on a benzothiazole derivative.
AB  - A simple benzothiazole fluorescent chemosensor was developed for the fast
      sequential detection of Cu2+ and biothiols through modulating the excited-state
      intramolecular proton transfer (ESIPT) process. The compound 1 exhibits highly
      selective and sensitive fluorescence "on-off" recognition to Cu2+ with a 1:1
      binding stoichiometry by ESIPT hinder. The in situ generated 1-Cu2+ complex can
      serve as an "on-off" fluorescent probe for high selectivity toward biothiols via
      Cu2+ displacement approach, which exerts ESIPT recovery. It is worth pointing out
      that the 1-Cu2+ complex shows faster for cysteins (within 1min) than other
      biothiols such as homocysteine (25min) and glutathione (25min). Moreover, the
      compound 1 displays 160nm Stoke-shift for reversibly monitoring Cu2+ and
      biothiols. In addition, the probe is successfully used for fluorescent cellular
      imaging. This strategy via modulation the ESIPT state has been used for
      determination of Cu2+ and Cys with satisfactory results, which further
      demonstrates its value of practical applications.

PMID- 29073544
TI  - Digital logic circuit based on two component molecular systems of BSA and salen.
AB  - A new fluorescent molecular probe 1 was designed and constructed by combining
      bovine serum albumin (BSA) and N,N'-bis(salicylidene)ethylenediamine (salen).
      Stimulated by Zn2+, tris, or EDTAH2Na2, the distance between BSA and salen was
      regulated, which was accompanied by an obvious change in the fluorescence
      intensity at 350 or 445nm based on Forster resonance energy transfer. Moreover,
      based on the encoding binary digits in these inputs and outputs applying positive
      logic conventions, a monomolecular circuit integrating one OR, three NOT, and
      three YES gates, was successfully achieved.

PMID- 29073545
TI  - In vitro structure-specific Zn(II)-induced adipogenesis and structure-function
      bioreactivity correlations.
AB  - The advent of Zn(II) metallodrugs in metabolic syndrome pathologies generates a
      strong challenge toward synthetic endeavors targeting well-defined, atoxic and
      biologically active binary/ternary species of Zn(II). Proper formulation of that
      metal ion's coordination sphere sets the stage for construction of appropriately
      configured Schiff ligands based on tromethamine and variably modified vanillin
      core components. The arising Schiff ligands react with Zn(II) in a defined
      stoichiometry, thereby delivering new binary Zn(II)-L species with defined
      physicochemical properties. Analytical (elemental), spectroscopic (FT-IR,
      Thermogravimetric Analysis) and crystallographic techniques attest to the
      distinct nature of the derived binary-ternary materials, bearing defined Zn(II):L
      molecular stoichiometry, variable nuclearity, charge, bulk and balance mix of
      hydrophilicity-hydrophobicity, thereby providing the physicochemical profile
      based on which biological studies could ensue. The structurally based selection
      of species was applied onto in vitro 3T3-L1 cultures, essentially exploring
      toxicity, migration, morphology, cell differentiation and maturation. The
      systematic effort toward comparative work on appropriately defined Zn(II) species
      and insulin in inducing adipogenesis reveals the salient structural features in
      the Schiff family of ligands configuring Zn(II) so as to promote complex
      formation sufficient to engage biomolecular targets during the process of
      initiation and maturation. Molecular targets of importance in adipogenesis were
      examined under the influence of Zn(II) and their expression levels suggest the
      structural composition that a Zn(II) ion might have to optimally pursue cell
      differentiation. Thus, a well-defined selection of binary Zn(II)-L species is
      tightly associated with the incurred bioactivity, thereby setting the stage for
      the development of efficient Zn(II) metallodrugs to combat Diabetes mellitus II.

PMID- 29073546
TI  - Jejunal perforation as an unusual presentation of total colonic aganglionosis in
      a neonate: A case report.
AB  - INTRODUCTION: Neonatal intestinal perforation usually occurs at distal small
      bowel secondary to distal bowel obstruction. The aim of this report is to
      describe an unusual case of total colonic aganglionosis with an initial
      presentation of proximal jejunal perforation. PRESENTATION OF CASE: A male
      newborn presented with jejunal perforation on the fifth day of life and was
      treated by laparoscopic primary repair. Abdominal distention persisted
      postoperatively, and radiological examination revealed an obstruction near the
      terminal ileum. Laparotomy showed a transition zone 30-cm proximal to the
      ileocecal valve, and diverting ileostomy and appendiceal biopsy was performed.
      Permanent section demonstrated the complete absence of ganglion cells in the
      appendix and total colonic aganglionosis was strongly suspected. DISCUSSION:
      Contrary to the classic teaching, proximal bowel perforation can occur in case of
      far distal obstruction, and careful distal evaluation would direct more
      appropriate surgical treatment option. CONCLUSIONS: Total colonic aganglionosis
      can present as a proximal bowel perforation. Careful distal evaluation can
      provide diagnostic clues in cases of proximal intestinal perforation. Appendiceal
      biopsy is a reliable tool for evaluating suspected total colonic aganglionosis,
      but multiple colonic and rectal biopsies should be obtained to confirm the
      diagnosis.

PMID- 29073547
TI  - Rectovaginal fistula after low anterior resection for rectal cancer healed by
      nonoperative treatment.
AB  - BACKGROUND: Rectovaginal fistula (RVF) is a serious complication after colorectal
      anastomosis using a double-stapling technique. RVF following this procedure has
      been considered to be refractory to conservative treatment. CASE PRESENTATION: A
      75-year-old woman who underwent laparoscopy-assisted low anterior resection for
      early rectal cancer developed RVF on the 12th postoperative day. Conservative
      treatment was chosen and was successful. She was discharged from the hospital
      after 3 weeks with a normal oral diet. Colonoscopy on the 50th postoperative day
      showed that the RVF was closed. CONCLUSION: Conservative treatment may be
      effective for RVF after colorectal anastomosis using a double-stapling technique
      when there is no evidence of defecation through the vagina.

PMID- 29073548
TI  - Anatomic variation of the relation between the facial nerve and the
      retromandibular vein during superficial parotidectomy: A rare case report.
AB  - INTRODUCTION: Identification and preservation of the facial nerve (FN) is a major
      challenge when performing parotidectomy. Anatomic variations of the relation
      between the FN and the retromandibular vein (RMV) pose a high risk of nerve
      injury and bleeding during the operation. PRESENTATION OF CASE: An unusual
      anatomic variation of the relation between the FN and the RMV was unexpectedly
      detected during superficial parotidectomy. The operation was uneventful. A
      meticulous review of the recent literature was conducted as well. DISCUSSION:
      Variations of the relation between the FN and the RMV are mainly identified
      during the operation, since when performing parotidectomy, surgeons typically
      detect all the FN branches by locating the RMV. Such kind of variations, are not
      as rare as considered and their presence complicates parotid surgery and
      increases the potentiality of nerve injury and hemorrhage. CONCLUSION: Surgeons'
      deep knowledge and perpetual awareness concerning the probable anatomic
      variations of the relation between the FN and the RMV combined with detailed
      exposure of the operative field and of the relationship between these adjacent
      anatomical structures lead to safe parotid surgery.

PMID- 29073549
TI  - Gastric outlet obstruction by a lost gallstone: Case report and literature
      review.
AB  - INTRODUCTION: Spilled gallstones from a laparoscopic cholecystectomy can be a
      source of significant morbidity, most commonly causing abscesses and fistulae.
      Preventative measures for loss, careful removal during the initial surgery, and
      good documentation of any concern for remaining intraperitoneal stones needs to
      be performed with the initial surgery. CASE REPORT: An 80-year-old male with a
      history of complicated biliary disease resulting in a cholecystectomy presented
      to general surgery clinic with increasing symptoms of gastric outlet obstruction.
      CT imaging was concerning for a malignant process despite negative biopsies. A
      distal gastrectomy and Billroth II reconstruction was performed and final
      pathology showed dense inflammation with a single calcified stone incarcerated
      within the gastric wall of the inflamed pylorus and no malignancy. DISCUSSION:
      Stones lost during laparoscopic cholecystectomy are not innocuous and
      preventative measures for loss, careful removal during the initial surgery, and
      good documentation of any concern for remaining intraperitoneal stones.
      CONCLUSION: This is the first case of gastric outlet obstruction caused by an
      intramural obstruction of the pylorus from a spilled gallstone during a
      laparoscopic cholecystectomy and subsequent inflammation. This is an etiology
      that must be considered in new cases of gastric outlet obstruction and can mimic
      malignancy.

PMID- 29073550
TI  - Ruptured gastroepiploic artery aneurysm: A case report.
AB  - INTRODUCTION: Gastroepiploic artery aneurysms are extremely rare, with few
      reported cases in the literature. The risk of rupture however, is high and thus
      warrants attention. PRESENTATION OF CASE: Here we present a rare case of a women
      who presented to the emergency department in shock and was found to have a
      ruptured gastroepiploic artery aneurysm during surgical exploration. Suture
      ligation of the aneurysm was completed. DISCUSSION: Although rare, gastroepiploic
      artery aneurysms have up to a 90% rate of rupture and therefore require
      intervention. A laparoscopic approach has been described however, in cases where
      rupture has occurred, urgent laparotomy and control of hemorrhage is needed.
      CONCLUSION: We describe a rare case of a ruptured gastroepiploic aneurysm that
      was successfully managed with urgent laparotomy and aneurysmal resection.

PMID- 29073551
TI  - Medial opening wedge high tibial osteotomy in patients with posttraumatic medial
      tibial plateau bone defect: A case report.
AB  - INTRODUCTION: Traumatic uncontained bone defect in the knee joint is one of the
      most serious knee injuries. As the knee joint is the main weight-bearing joint of
      the body, the problem of weight loading should be addressed while restoring the
      bone defect. However, no consensus exists regarding the treatment of this injury.
      PRESENTATION OF CASE: Two patients in separate cases initially sustained
      traumatic uncontained proximal tibial bone defects secondary to passenger traffic
      accidents. After recovery from the initial trauma, these patients underwent
      medial opening wedge high tibial osteotomy (MOWHTO) and femoral head allograft
      augmentation simultaneously. DISCUSSION: Treatment of traumatic uncontained bone
      defect in the knee joint should be considered separately as tumorous or
      osteoarthritic bone defects. Especially, the effects of the defective supporting
      soft tissue structures should be considered. CONCLUSION: We considered that
      MOWHTO was capable of solving problems of both bone stock restoration and weight
      loading. After the operation, the patients' knee joint pain was relieved and
      stable ambulation was possible.

PMID- 29073552
TI  - Chemotherapy-induced cognitive impairments: White matter pathologies.
AB  - Whilst chemotherapeutic agents show promising results in the amelioration of
      cancerous tumors, patients often experience cognitive disturbances associated
      with chemotherapy long after treatment has ceased. Research has suggested that
      the structural integrity of white matter fibres in the brain are susceptible to
      the harmful effects of chemotherapy. Post-chemotherapy, white matter tracts often
      display altered morphology with a reduction in glial cells such as
      oligodendrocytes. Demyelination, gliosis and leukoencephalopathy during or post
      chemotherapy is associated with changes in processing speed and IQ. Thus,
      understanding the relationship between chemotherapy, white matter damage and
      cognition is warranted. This review presents evidence for chemotherapy induced
      white matter damage highlighting the importance of implementing behavioral and
      pharmological strategies to prevent or reverse such acute toxicity in the brain.

PMID- 29073553
TI  - Interactions of perfluoroalkyl substances with a phospholipid bilayer studied by
      neutron reflectometry.
AB  - The interactions between perfluoroalkyl substances (PFASs) and a phospholipid
      bilayer (1,2-dimyristoyl-sn-glycero-3-phosphocholine) were investigated at the
      molecular level using neutron reflectometry. Representative PFASs with different
      chain length and functional groups were selected in this study including:
      perfluorobutane sulfonate (PFBS), perfluorohexanoate (PFHxA), perfluorohexane
      sulfonate (PFHxS), perfluorononanoate (PFNA), perfluorooctane sulfonate (PFOS),
      and perfluorooctane sulfonamide (FOSA). All PFASs were found to interact with the
      bilayer by incorporation, indicating PFAS ability to accumulate once ingested or
      taken up by organisms. The interactions were observed to increase with chain
      length and vary with the functional group as SO2NH2(FOSA)>SO2O-(PFOS)>COO-(PFNA).
      The PFAS hydrophobicity, which is strongly correlated with perfluorocarbon chain
      length, was found to strongly influence the interactions. Longer chain PFASs
      showed higher tendency to penetrate into the bilayer compared to the short-chain
      compounds. The incorporated PFASs could for all substances but one (PFNA) be
      removed from the lipid membrane by gentle rinsing with water (2mLmin-1). Although
      short-chain PFASs have been suggested to be the potentially less bioaccumulative
      alternative, we found that in high enough concentrations they can also disturb
      the bilayer. The roughness and disorder of the bilayer was observed to increase
      as the concentration of PFASs increased (in particular for the high
      concentrations of short-chain substances i.e. PFHxA and PFBS), which can be an
      indication of aggregation of PFASs in the bilayer.

PMID- 29073554
TI  - Identifying trends in hydration behavior for modifications to the hydrophobicity
      of poly(n-isopropylacrylamide).
AB  - Poly(n-isopropylacrylamide), PNIPAM, is a thermo-responsive polymer that has been
      thoroughly studied for its many applications, such as drug delivery and
      actuators. Below the lower critical solution temperature (LCST), PNIPAM is well
      hydrated in the elongated conformation. The transition occuring at the LCST
      results in a less hydrated collapsed state above the LCST. This volume phase
      transition is dependent upon the hydration of the polymer and its hydrophobicity.
      Some research has been done on potential modifications of PNIPAM for
      applications, but until now there has not been a study of the hydration
      properties as a function of hydrophobicity. The work presented in this paper
      applies a Voronoi analysis of the hydration of PNIPAM, as well as PNIPAM with
      other alkyl substituents. We show from classical MD simulations that increasing
      hydrophobicity can increase the volume phase change, but there is a lower limit
      to this trend. Additionally, replica exchange molecular dynamics were conducted
      on PNIPAM showing a fluctuation between elongated and collapsed states near the
      LCST.

PMID- 29073555
TI  - Effects of synergistic and non-synergistic anions on the iron binding site from
      serum transferrin: A molecular dynamic simulation analysis.
AB  - The role of the anions in transferrin chemistry highlights the importance of the
      anion binding site in transferrin family. A synergistic anion as carbonate is an
      anion that is required for iron binding by transferrin while non-synergistic
      anions do not act as the synergistic anions to promote iron binding, but affect
      the iron binding and release. Some questions remain unclear about the difference
      between synergistic and non-synergistic anion functions. In the present work,
      molecular dynamic simulation techniques were employed in order to gain access
      into a molecular level understanding of the iron binding site of the human serum
      transferrin during the synergistic and non-synergistic anion binding. For this
      purpose, a comparative analysis was performed to illustrate the observed changes.
      In addition to the comparison between the synergistic and non-synergistic anions,
      structural differences between two synergistic anions, Carbonate and Oxalate were
      studied. Meanwhile,the simulation of the open (Apo), partially closed (Carbonate)
      and fully closed (Carbonate-Fe) forms of the transferrin structure allows a
      direct comparison between the iron binding site of these three states.On the
      basis of results, synergistic anions form high affinity binding site, while non
      synergistic anions act like Apo state of the transferrin structure and change the
      proper conformation of the binding site. In order to act as a synergistic anion
      and form high affinity binding site, anion stereochemistry and interactions must
      be able to achieve a Carbonate-like configuration. Carbonate complex showed the
      highest binding affinity and electrostatic energy is the major favorable
      contributor to synergistic anion-transferrin interaction. Carbonate and
      Oxalatecomplexes as synergistic anions have many features in common, without a
      significant change in the transferrin structure. Only the residues in the
      vicinity of the binding site showed a little different conformation depending on
      whether the synergistic anion is Carbonate orOxalate.Finally, the results show
      thatASP63, GLY65 and HIS249 residues have the maximum displacement during the
      Carbonate and iron binding. ASP63 and HIS249 are the residues, which are
      coordinated to the iron and GLY65 is in the second shell residuesof the
      transferrin structure.

PMID- 29073556
TI  - Glucocorticoid may influence amyloid beta metabolism in patients with depression.
AB  - Epidemiological studies have demonstrated that depression may be a risk factor
      for Alzheimer's disease (AD); however, the biological mechanisms of the
      transition from depression to AD are still not clear. Changes of amyloid beta
      protein (Abeta) metabolism and increased glucocorticoid (GC) levels have been
      found in both depression and AD. Moreover, several studies in animal models have
      demonstrated that GC administration changes Abeta metabolism. To reveal whether
      GC affects amyloid metabolism in patients with depression, we evaluated serum
      levels of Abeta40, Abeta42 and cortisol at admission in 187 inpatients with major
      depressive disorder (MDD) and 224 healthy comparisons. Additionally, we re
      evaluated the serum levels of Abetas in 27 patients with MDD 1 year later. The
      results of multiple regression analyses revealed that serum cortisol and Abeta
      levels are not correlated at the time of admission. However, serum cortisol
      levels at admission correlated with serum Abeta42 levels and Abeta40/Abeta42
      ratio 1 year later. These findings suggest that increased cortisol in patients
      with MDD may influence the metabolism of Abeta over prolonged periods of time.

PMID- 29073558
TI  - Balancing carbon/nitrogen ratio to improve nutrients removal and algal biomass
      production in piggery and brewery wastewaters.
AB  - To improve nutrients removal from wastewaters and enhance algal biomass
      production, piggery wastewater was mixed with brewery wastewaters. The results
      showed that it was a promising way to cultivate microalga in piggery and brewery
      wastewaters by balancing the carbon/nitrogen ratio. The optimal treatment
      condition for the mixed piggery-brewery wastewater using microalga was piggery
      wastewater mixed with brewery packaging wastewater by 1:5 at pH 7.0, resulting in
      carbon/nitrogen ratio of 7.9, with the biomass concentration of 2.85 g L-1, and
      the removal of 100% ammonia, 96% of total nitrogen, 90% of total phosphorus, and
      93% of chemical oxygen demand. The application of the established strategies can
      enhance nutrient removal efficiency of the wastewaters while reducing microalgal
      biomass production costs.

PMID- 29073559
TI  - Effect of pyrolysis temperature on chemical form, behavior and environmental risk
      of Zn, Pb and Cd in biochar produced from phytoremediation residue.
AB  - This study aimed to evaluate the chemical forms, behavior and environmental risk
      of heavy metal (HMs) Zn, Pb and Cd in phytoremediation residue (PMR) pyrolyzed at
      350  degrees C, 550  degrees C and 750  degrees C, respectively. The behavior of
      HMs variation during the PMR pyrolysis process was analyzed and the potential HMs
      environmental risk of phytoremediation residue biochars (PMB) was assessed which
      was seldom investigated before. The results showed that the pyrolysis temperature
      increase decreased the soluble/exchangeable HMs fraction and alleviated the HMs
      bioavailability. When the temperature was over 550  degrees C, the adsorbed
      Zn(II), Pb(II) and Cd(II) were turned into oxides forms and concentrated in PMB
      with more stable forms exhibiting lower risk assessment code and potential
      ecological risk index. The ecotoxicity test showed higher pyrolysis temperature
      favored the reduction of PMB ecotoxicity. It is suggested that pyrolysis
      temperature above 550 degrees C may be suitable for thermal treatment of PMR with
      acceptable environmental risk.

PMID- 29073560
TI  - Solvo-thermal in situ transesterification of wet spent coffee grounds for the
      production of biodiesel.
AB  - This work addresses non-catalytic biodiesel production from spent coffee ground
      (SCG) by integrating solvo-thermal effect of 1,2-dichloroethane (DCE) with in
      situ transesterification over 160  degrees C. The SCG water content has a
      positive effect on the DCE hydrolysis up to 60 wt% due to the bimolecular
      substitution mechanism. The hydrolysis gives an acidic environment favorable for
      cellulose decomposition, SCG particle size reduction and lipid conversion. The
      optimal fatty acid ethyl ester yield was 11.8 wt% based on the mass of dried SCG
      with 3.36 ml ethanol and 3.16 ml DCE at 196.8  degrees C through the response
      surface methodology. Using the solvo-thermal effect, direct utilization of wet
      SCG as a biodiesel feedstock provides not only economic feasibility without using
      drying process and additional acid catalyst but also environmental advantage of
      recycling the municipal waste.

PMID- 29073557
TI  - Affect-based profiles of bulimia nervosa: The utility and validity of indicators
      assessed in the natural environment.
AB  - Theoretical conceptualizations of bulimia nervosa (BN) emphasize the role of
      emotion dysregulation in the development and maintenance of symptoms, which has
      been supported by ecological momentary assessment studies. Given the importance
      of affective disturbances in BN, this study aimed to classify a sample of adult
      women with BN (N = 130) based on primarily momentary affective indicators,
      including negative and positive affect, negative and positive affective lability,
      and depression. Participants completed baseline assessments followed by a two
      week ecological momentary assessment protocol. Latent profile analysis revealed
      four groups: (1) a "stable normal" group characterized by low affective lability
      and intensity; (2) a "stable depressed" group characterized by low affective
      lability and higher affect intensity; (3) an "unstable normal" group
      characterized by higher affective lability but lower affect intensity; and (4) an
      "unstable depressed" group characterized by higher affective lability and
      intensity. The stable depressed group evidenced the highest levels of eating
      psychopathology, borderline personality traits, and childhood trauma history,
      while the stable normal group generally evidenced the lowest levels of
      psychopathology. The findings demonstrate significant heterogeneity in the
      topography of affect experienced by individuals with BN, and suggest that
      chronic, intense negative affect may be particularly important to address in
      treatment.

PMID- 29073561
TI  - Evidence for programmed odontoblast process retraction after dentine exposure in
      the rat incisor.
AB  - OBJECTIVE: To re-examine the morphology and potential functions of odontoblasts
      in intact rat incisors and after cavity preparation into dentine. DESIGN: Intact
      incisors were fixed, decalcified, snap frozen and sectioned (10MUm), before
      staining with rhodamine phalloidin or antibodies for cyto-skeletal proteins:
      vimentin and actin, ion transporter: NaK-ATPase, and dendritic cell marker: OX6.
      Samples with cavity were processed similarly and stained for actin and vimentin
      before comparing the lengths of odontoblast processes (OP) at baseline, 3h and
      24h (n=5 for each group). RESULTS: Actin was expressed through the full length of
      OP, while vimentin immunoreactivity was not uniform, with 4 distinct regions. OP
      showed morphological complexity with fine branches emanating within different
      regions of dentine. Novel actin-positive tree-like OP were identified within
      predentine which reduced in intensity and length toward the incisal portion of
      the tooth. Specimens with cavities showed time-dependant pulpal retraction of OP.
      CONCLUSIONS: Differences in structural antibody expression suggest functional
      variations in OP within different regions of dentine. The role of actin positive
      OP in predentine is not known, but could be related to dentine deposition,
      cellular stability or sensing mechanisms. Cavity preparation into dentine was
      followed by programmed retraction of OP which could be controlled either
      mechanically by the spatial limitation of the OP within dentinal tubules or
      structurally by the presence of vimentin, in addition to actin, in the mid
      dentine.

PMID- 29073562
TI  - Dipeptidyl peptidase-4 inhibitor enhances restoration of salivary glands impaired
      by obese-insulin resistance.
AB  - OBJECTIVE: Chronic high-fat diet consumption causes not only obese- insulin
      resistance, but also leads to pathological changes in salivary glands, including
      increased mitochondrial dysfunction, apoptosis, oxidative stress, and
      inflammation. Dipeptidyl peptidase-4 inhibitor (vildagliptin) is an oral anti
      diabetic drug, using for treatment of type 2 diabetes. Vildagliptin has been
      shown to exert beneficial effects on several organs in cases of obese-insulin
      resistant condition. However, the effect of vildagliptin on salivary glands
      impaired by obese-insulin resistance has not been investigated. The hypothesis in
      this study is that vildagliptin confers beneficial effects on the salivary gland
      impaired by obese-insulin resistance via decreasing mitochondrial dysfunction,
      apoptosis, oxidative stress, and inflammation. DESIGN: Twenty-four male Wistar
      rats were divided into two groups. Each group was fed with either a normal (ND;
      n=8) or a high fat diet (HFD; n=16) for 16 weeks. At week 13, the HFD-fed rats
      were subdivided into 2 subgroups to receive either a vehicle or vildagliptin
      (3mg/kg/day) for 28days via gavage feeding. ND-fed rats were treated with the
      vehicle. At the end of treatment, metabolic parameters were examined, and rats
      were killed. Submandibular glands were removed to appraise inflammatory markers,
      apoptosis and mitochondrial function. RESULTS: Vehicle-treated HFD-fed rats
      developed obese-insulin resistance with an increase in oxidative stress,
      inflammation, apoptosis, and mitochondrial dysfunction in the salivary glands.
      Vildagliptin therapy reduced oxidative stress, inflammation, apoptosis and
      mitochondrial dysfunction in salivary gland of HFD-fed rats. CONCLUSION:
      Vildagliptin prevented salivary gland injury occurring due to obese-insulin
      resistance.

PMID- 29073563
TI  - Effect of chronic stress on capsaicin-induced dental nociception in a model of
      pulpitis in rats.
AB  - OBJECTIVE: Chronic stress can alter nociceptive sensitivity. However, the effect
      of stress exposure on dental nociception has been less addressed. Therefore, the
      present study investigated the effects of chronic exposures to some social and
      psychological stresses on pulpal nociceptive responses. DESIGN: The stress groups
      were constructed as follows: forced swimming (n=6), restraint (n=6), and mild
      (n=10) and severe (n=15) crowding stresses. Rats were subjected to stress for 1h
      per day for a week. At the end of the stress session, pulp irritation was induced
      by intradental application of capsaicin (100MUg). There were another capsaicin or
      capsaicin plus stress training groups that received articaine 5min before the
      administration of capsaicin. Nociceptive responses were recorded for 40min. The
      time (ins) of continuous shaking of the lower jaw and excessive grooming and
      rubbing of the mouth near the procedure site was measured as nociceptive
      behaviors. Data was analyzed using one-way analysis of variance (ANOVA) followed
      by post hoc Tukey's test. RESULTS: Significant nociceptive responses were evoked
      by the administration of capsaicin. Exposures to forced swimming (p<0.01),
      restraint (p<0.001), and both mild and severe crowding stresses (p<0.05)
      exaggerated capsaicin-induced nociceptive reaction. There was, however, no
      significant difference in nociceptive reaction time between the different stress
      groups. Articaine buccal infiltration attenuated nociceptive time in capsaicin
      and capsaicin plus stress training groups (p<0.001). CONCLUSIONS: The current
      data support the association between chronic stress exposures and nociceptive
      behavior following intradental capsaicin administration.

PMID- 29073564
TI  - Impact of disposal of dredged material on sediment quality in the Kaohsiung Ocean
      Dredged Material Disposal Site, Taiwan.
AB  - Kaohsiung Ocean Dredged Material Disposal Site (KODMDS) that located in the
      southwest offshore of Taiwan, has been annually disposed about 500,000 ton
      dredged sediments of Kaohsiung Harbor from 2003 to 2012. Five sediment cores
      collected from KODMDS and three from nearby reference sites were analyzed to
      evaluate their sedimentation rates, vertical profiles of heavy metal, and heavy
      metal pollution indices to assess the impact of dumping harbor dredged sediments
      into the ocean on the sediment quality in KODMDS. The sedimentation rate of 0.24
      cm/y was estimated by the 210Pb method, which means that the effected depth of
      the top layer of a core of D1 was affected in the period of dumping dredging
      sediments. The vertical distribution of heavy metals in the sediment cores from
      KODMDS showed the concentrations of most heavy metals were slightly elevated in
      the top layers of the sediment cores, which may be affected by the dumping of
      harbor dredged sediments. According to the analyzed results of the heavy metal
      pollution indices, the level of heavy metal pollution, the potential eco-toxicity
      and the potential ecological risk of the sediments in KODMDS exhibited only a
      slight increase, which indicated that the increase in concentration of heavy
      metals may potentially pose the insignificant impact on benthos inhabiting the
      disposal site.

PMID- 29073565
TI  - Preparation of stable tetraethylenepentamine-modified ordered mesoporous silica
      sorbents by recycling natural Equisetum ramosissimum.
AB  - It is well-known that global warming of the earth is caused by the progressive
      increase of CO2 concentration in the environment due to the huge utilization of
      fossil fuels. As a result, the development of an efficient and economic method to
      capture CO2 from large stationary sources, such as coal-fired power plants,
      cement and steel factories, and so on is urgent. In this study, ordered
      mesoporous silicas (E-SBA-15) have been prepared by using Equisetum ramosissimum
      plants as the silica sources and their subsequently incorporating with amino
      containing compounds (tetraethylenepentamine, TEPA) and stabilizers (titanium
      isopropoxide, TIP). A variety of different spectroscopic and analytical
      techniques, such as nitrogen adsorption-desorption isotherms, low-angle X-ray
      diffraction (XRD), transmission electron microscopy (TEM), Fourier-transformed
      infrared (FTIR) spectroscopy, and thermogravimetric analysis (TGA) are used to
      characterize the physicochemical properties of various materials. CO2 adsorption
      capacities of prepared sorbents at 75  degrees C are obtained by TGA at
      atmospheric pressure. Among all sorbents, TEPA impregnated E-SBA-15 sorbents
      possess the highest CO2 sorption capacity (1.60 mmol CO2 g-1sorbent) under
      ambient pressure using dry 15% CO2. However, TEPA/TIP incorporated E-SBA-15
      sorbents exhibit enhanced durability during repeated sorption-desorption cycles
      compared to the above-mentioned sorbents. This significant enhancement in the
      stability of CO2 sorption-desorption process is most likely due to the decreased
      decomposition/leaching of TEPA which is restricted via the steric effect of TIP.
      These synthesized sorbents from inexpensive resources (agricultural waste)
      exhibit good sorbent capacity and surpassing regenerability, revealing a
      promising CO2 sorbent for the cost-effective applications in a cyclic adsorption
      process.

PMID- 29073566
TI  - Enhancement of operating flux in a membrane bio-reactor coupled with a mechanical
      sieve unit.
AB  - Filtration flux is one of the key factors in regulating the performance of
      membrane bio-reactors (MBRs) for wastewater treatment. In this study, we explore
      the effectiveness of a mechanical sieve unit for effective flux enhancement
      through retardation of the fouling effect in a modified MBR system (SiMBR). In
      brief, the coarse sieve unit having 100 MUm and 50 MUm permits small size
      microorganism flocs to adjust the biomass concentration from the suspended basin
      to the membrane basin. As a result, the reduced biofouling effect due to the
      lowered biomass concentration from 7800 mg/L to 2400 mg/L, enables higher flux
      through the membrane. Biomass rejection rate of the sieve is identified to be the
      crucial design parameter for the flux enhancement through the incorporation of
      numerical simulations and operating critical-flux measurement in a batch reactor.
      Then, the sieve unit is prepared for 10 L lab-scale continuous SiMBR based on the
      correlation between sieve pore size and biomass rejection characteristics. During
      continuous operation of lab-scale SiMBR, biomass concentration is maintained with
      a higher biomass concentration in the aerobic basin (7400 mg/L) than that in the
      membrane basin (2400 mg/L). In addition, the SiMBR operations are conducted using
      three different commercial hollow fiber membranes to compare the permeability to
      that of conventional MBR operations. For all cases, the modified MBR having a
      sieve unit clearly results in enhanced permeability. These results successfully
      validate that SiMBR can effectively improve flux through direct reduction of
      biomass concentration.

PMID- 29073567
TI  - Impact of the Fenton-like treatment on the microbial community of a diesel
      contaminated soil.
AB  - Fenton-like treatment (FLT) is an ISCO technique relying on the iron-induced H2O2
      activation in the presence of additives aimed at increasing the oxidant lifetime
      and maximizing iron solubility under natural soil pH conditions. The efficacy of
      FLT in the clean-up of hydrocarbon-contaminated soils is well established at the
      field-scale. However, a better assessment of the impact of the FLT on density,
      diversity and activity of the indigenous soil microbiota, might provide further
      insights into an optimal combination between FLT and in-situ bioremediation
      (ISB). The aim of this work was to assess the impacts of FLT on the microbial
      community of a diesel-contaminated soil collected nearby a gasoline station.
      Different FLT conditions were tested by varying either the H2O2 concentrations (2
      and 6%) or the oxidant application mode (single or double dosage). The impact of
      these treatments on the indigenous microbial community was assessed immediately
      after the Fenton-like treatment and after 30, 60 and 90 d and compared with
      enhanced natural attenuation (ENA). After FLT, a dramatic decrease in bacterial
      density, diversity and functionality was evident. Although in microcosms with
      double dosing at 2% H2O2 a delayed recovery of the indigenous microbiota was
      observed as compared to those subjected to single oxidant dose, after 60 d
      incubation the respiration rate increased from 0.036 to 0.256 MUg CCO2 g-1soil h
      1. Irrespective of the oxidant dose, best degradation results after 90 d
      incubation (around 80%) were observed with combined FLT, relying on double
      oxidant addition, and bioremediation.

PMID- 29073568
TI  - Assessment of androgen receptor agonistic/antagonistic effects on 25 chemicals in
      household applicants by OECD in vitro stably transfected transcriptional
      activation assays.
AB  - The aim of this study is to assess the androgen receptor (AR)
      agonistic/antagonistic effects on various chemicals, which are used in household
      products including cleaning agents and wetted tissues by in vitro OECD test
      guideline No. 458 (using AR-EcoScreenTM cell line) and the me-too test method
      (using 22Rv1cell line), which was adopted as OECD project No. 4.99. All chemicals
      were not determined as AR agonists. However alpha-dodecyl-omega-hydroxypoly
      (oxyethylene) and 3-iodo-2-propynyl butylcarbamate have shown a weak AR
      antagonistic effects with IC50 values of 2.18 +/- 0.12 and 4.26 +/- 0.17 MUg/ml
      via binding affinity to AR in only 22Rv1/mouse mammary tumor virus using AR
      transcriptional activation assay, because of their different cytotoxicity on each
      applied cell line. This report firstly provides information about
      agonistic/antagonistic effects against human AR of various chemicals including
      surfactants and biocides by OECD in vitro stably transfected transcriptional
      activation assays. However, further in vivo and human model studies are needed to
      confirm their adverse effects.

PMID- 29073569
TI  - Seasonal variability of natural water chemistry affects the fate and behaviour of
      silver nanoparticles.
AB  - Understanding the environmental behaviour of nanoparticles (NPs) after release
      into aquatic systems is essential to predict the environmental implications of
      nanotechnology. Silver nanoparticles (AgNPs) represent a major class of
      engineered NPs with a significant potential for environmental impact. Therefore,
      investigating their transformations in natural waters will help predict their
      long term environmental fate and behaviour. AgNPs were characterized in natural
      lake water collected seasonally from the same freshwater source, using column
      microcosms to assess their behaviour and transport at different depths. Building
      on our previous work using similar systems with synthetic waters, the influence
      of water chemistry and NP surface modifications on colloidal stability and
      dissolution in natural lake water over time was investigated. A simple
      sedimentation-diffusion model parameterized by the particle properties and total
      Ag concentration was successfully used to understand AgNPs transport behaviour.
      PVP coated AgNPs remained colloidally stable, with their transport in the water
      column dominated by diffusion, and exhibited no significant or substantial
      changes in data or model parameters for different seasons. Citrate coated AgNPs
      were susceptible to rapid aggregation, sedimentation, dissolution and
      reprecipitation; their transport in the water column was determined by both
      diffusion and sedimentation.

PMID- 29073570
TI  - A new method for wind speed forecasting based on copula theory.
AB  - How to determine representative wind speed is crucial in wind resource
      assessment. Accurate wind resource assessments are important to wind farms
      development. Linear regressions are usually used to obtain the representative
      wind speed. However, terrain flexibility of wind farm and long distance between
      wind speed sites often lead to low correlation. In this study, copula method is
      used to determine the representative year's wind speed in wind farm by
      interpreting the interaction of the local wind farm and the meteorological
      station. The result shows that the method proposed here can not only determine
      the relationship between the local anemometric tower and nearby meteorological
      station through Kendall's tau, but also determine the joint distribution without
      assuming the variables to be independent. Moreover, the representative wind data
      can be obtained by the conditional distribution much more reasonably. We hope
      this study could provide scientific reference for accurate wind resource
      assessments.

PMID- 29073571
TI  - Estimating the health benefits of planned public transit investments in Montreal.
AB  - BACKGROUND: Since public transit infrastructure affects road traffic volumes and
      influences transportation mode choice, which in turn impacts health, it is
      important to estimate the alteration of the health burden linked with transit
      policies. OBJECTIVE: We quantified the variation in health benefits and burden
      between a business as usual (BAU) and a public transit (PT) scenarios in 2031
      (with 8 and 19 new subway and train stations) for the greater Montreal region.
      METHOD: Using mode choice and traffic assignment models, we predicted the
      transportation mode choice and traffic assignment on the road network.
      Subsequently, we estimated the distance travelled in each municipality by mode,
      the minutes spent in active transportation, as well as traffic emissions.
      Thereafter we estimated the health burden attributed to air pollution and road
      traumas and the gains associated with active transportation for both the BAU and
      PT scenarios. RESULTS: We predicted a slight decrease of overall trips and
      kilometers travelled by car as well as an increase of active transportation for
      the PT in 2031 vs the BAU. Our analysis shows that new infrastructure will reduce
      the overall burden of transportation by 2.5 DALYs per 100,000 persons. This
      decrease is caused by the reduction of road traumas occurring in the inner
      suburbs and central Montreal region as well as gains in active transportation in
      the inner suburbs. CONCLUSION: Based on the results of our study, transportation
      planned public transit projects for Montreal are unlikely to reduce drastically
      the burden of disease attributable to road vehicles and infrastructures in the
      Montreal region. The impact of the planned transportation infrastructures seems
      to be very low and localized mainly in the areas where new public transit
      stations are planned.

PMID- 29073572
TI  - A critical review of ferrate(VI)-based remediation of soil and groundwater.
AB  - Over the past few decades, diverse chemicals and materials such as mono- and
      bimetallic nanoparticles, metal oxides, and zeolites have been used for soil and
      groundwater remediation. Ferrate (FeVIO42-) has been widely employed due to its
      high-valent iron (VI) oxo compound with high oxidation/reduction potentials.
      Ferrate has received attention for wide environmental applications including
      water purification and sewage sludge treatment. Ferrate provides great potential
      for diverse environmental applications without any environmental problems.
      Therefore, this paper provides comprehensive information on the recent progress
      on the use of (FeVIO42-) as a green material for use in sustainable treatment
      processes, especially for soil and water remediation. We reviewed diverse
      synthesis recipes for ferrates (FeVIO42-) and their associated physicochemical
      properties as oxidants, coagulants, and disinfectants for the elimination of a
      diverse range of chemical and biological species from water/wastewater samples. A
      summary of the eco-sustainable performance of ferrate(VI) in water remediation is
      also provided and the future of ferrate(VI) is discussed in this review.

PMID- 29073573
TI  - Exposure to traffic-generated air pollutants mediates alterations in brain
      microvascular integrity in wildtype mice on a high-fat diet.
AB  - Air pollution-exposure is associated with detrimental outcomes in the central
      nervous system (CNS) such as cerebrovascular disorders, including stroke, and
      neurodegenerative diseases. While the mechanisms of these CNS-related outcomes
      involved have not been fully elucidated, exposure to traffic-generated air
      pollutants has been associated with altered blood brain barrier (BBB) integrity
      and permeability. The current study investigated whether inhalation exposure to
      mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy
      3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were
      exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were
      randomly assigned to be exposed to either filtered air (FA) or MVE [100PM/m3
      vehicle emissions mixture: 30ug PM/m3 gasoline engine + 70ug PM/m3 diesel engine
      emissions; median size ~ 60nm; particle mass size distribution median of ~ 1um
      (range: < 0.5-20um)] for 6h/d, 7d/wk, for 30d. Using sodium fluorescein as a
      tracer, we observed a significant increase in BBB permeability in both HF + MVE
      exposed and HF + FA animals, compared to LF + FA controls. Exposure to HF + MVE
      also led to a significant increase plasma ox-LDL and ox-LDL scavenger receptors
      (LOX-1 and CD-36) expression in the cerebral vasculature. Histological analysis
      revealed decreased expression of TJ protein, claudin-5, associated with increased
      matrix metalloproteinase (MMP)-9 activity and oxidative stress in the cerebral
      vasculature of HF + MVE mice, compared to LF + MVE. Such findings indicate that
      inhalation exposure to traffic-generated pollutants, coupled with a HF diet,
      results in altered BBB integrity and increased ox-LDL signaling in the cerebral
      vasculature in a wildtype animal model.

PMID- 29073574
TI  - Effects of non-enzymatic glycation on the micro- and nano-mechanics of articular
      cartilage.
AB  - The mechanical properties of articular cartilage depend on the quality of its
      matrix, which consists of collagens and glycosaminoglycans (GAGs). The
      accumulation of advanced glycation end products (AGEs) can greatly affect the
      mechanics of cartilage. In the current study, we simulated the accumulation of
      AGEs by using L-threose to cross-link collagen molecules in the cartilage matrix
      (in vitro). The resulting changes in the mechanical properties (stiffness) of
      cartilage are then measured both at the micrometer-scale (using micro-indenter)
      and nanometer-scale (using indentation-type atomic force microscopy). Non
      enzymatic cross-linking within the cartilage matrix was confirmed by the browning
      of L-threose-treated samples. We observed > 3 times increase in the micro-scale
      stiffness and up to 12-fold increase in the nano-scale stiffness of the glycated
      cartilage in the peak pertaining to the collagen fibers, which is caused by
      cartilage network embrittlement. At the molecular level, we found that besides
      the collagen component, the glycation process also influenced the GAG
      macromolecules. Comparing cartilage samples before and after L-threose treatment
      revealed that artificially induced-AGEs also decelerate in vitro degradation
      (likely via matrix metalloproteinases), observed at both micro- and nano-scales.
      The combined observations suggest that non-enzymatic glycation may play multiple
      roles in mechanochemical functioning of articular cartilage.

PMID- 29073576
TI  - Major depressive disorder in patients with type 2 diabetes mellitus: Prevalence
      and clinical characteristics.
AB  - BACKGROUND: This study investigated the prevalence of major depressive disorder
      (MDD) among Taiwanese patients with type 2 diabetes mellitus (T2DM). METHODS: We
      enrolled patients with at least one service claim for ambulatory or inpatient
      care with a principal diagnosis of MDD and at least two service claims for
      ambulatory care or one service claim for inpatient care with a principal
      diagnosis of T2DM, as listed in Taiwan's National Health Insurance database.
      RESULTS: We enrolled 715,756 people from the general population (GP), 61,589
      patients with T2DM but without MDD, and 778 patients with both T2DM and MDD. The
      prevalence of MDD increased from 0.70% to 1.25% in the patients with T2DM,
      whereas it increased from 0.25% to 0.67% in the GP from 2000 to 2010. The higher
      prevalence of MDD was associated with the female sex, residing in the southern
      regions of Taiwan, and having comorbidities of cerebrovascular disease and
      anxiety disorder as well as higher comorbidity severity (Charlson comorbidity
      index, 1-2 and > 2). LIMITATIONS: One limitation is the use of secondary data on
      diagnoses of MDD and T2DM. Another limitation is that we could not access some
      crucial related variables. CONCLUSIONS: The prevalence of MDD was higher in the
      patients with T2DM than in the GP. In this study, the prevalence of MDD in the
      patients with T2DM was lower than that reported in Western countries.

PMID- 29073575
TI  - Relative merits and limiting factors for x-ray and electron microscopy of thick,
      hydrated organic materials.
AB  - Electron and x-ray microscopes allow one to image the entire, unlabeled structure
      of hydrated materials at a resolution well beyond what visible light microscopes
      can achieve. However, both approaches involve ionizing radiation, so that
      radiation damage must be considered as one of the limits to imaging. Drawing upon
      earlier work, we describe here a unified approach to estimating the image
      contrast (and thus the required exposure and corresponding radiation dose) in
      both x-ray and electron microscopy. This approach accounts for factors such as
      plural and inelastic scattering, and (in electron microscopy) the use of energy
      filters to obtain so-called "zero loss" images. As expected, it shows that
      electron microscopy offers lower dose for specimens thinner than about 1 um (such
      as for studies of macromolecules, viruses, bacteria and archaebacteria, and thin
      sectioned material), while x-ray microscopy offers superior characteristics for
      imaging thicker specimen such as whole eukaryotic cells, thick-sectioned tissues,
      and organs. The required radiation dose scales strongly as a function of the
      desired spatial resolution, allowing one to understand the limits of live and
      frozen hydrated specimen imaging. Finally, we consider the factors limiting x-ray
      microscopy of thicker materials, suggesting that specimens as thick as a whole
      mouse brain can be imaged with x-ray microscopes without significant image
      degradation should appropriate image reconstruction methods be identified.

PMID- 29073577
TI  - Prevalence of depression in cardiovascular patients in Iran: A systematic review
      and meta-analysis from 2000 to 2017.
AB  - BACKGROUND: In both developed and developing countries, cardiovascular disease is
      on the rise, representing nowadays one of the main challenges for the health
      systems worldwide. This increase generates relevant costs. The aim of this study
      was to conduct a systematic and meta-analytical review of the prevalence of
      depression in cardiovascular patients in Iran. METHODS: Articles written in
      English and Persian were searched from January 2000 to July 2017 in different
      scholarly databases. RESULTS: 12 studies were retained and included in the
      current meta-analysis. Selected studies were published between 2008 and 2016. The
      number of patients participating in these studies was 9292. Based on the random
      effects model, the prevalence of depression in cardiovascular patients in Iran
      was 47% [95% confidence interval or CI 38-56], I2=98.2% with P = 0.000. The
      relative risk (RR) of depression in cardiovascular patients yielded a value of
      1.30 [95%CI 1.05-1.62] with P < 0.001. Women are more at risk for depression than
      men. CONCLUSION: The current meta-analysis estimated the prevalence of depression
      among cardiovascular patients in Iran. The prevalence found computed by the
      present study is higher than the figures found in developed countries. Depression
      with cardiovascular disease causes many problems for these patients, and early
      diagnosis and treatment significantly helps in improving quality of life, as well
      as saving costs and resources.

PMID- 29073578
TI  - Long-term retention rates for antiepileptic drugs: A review of long-term
      extension studies and comparison with brivaracetam.
AB  - Antiepileptic drug (AED) retention rates are frequently reported in the
      literature and used to inform clinical decision-making, but methodological
      differences in the determination of retention rates make comparisons between
      trials difficult. Open-label extension (OLE) studies of AEDs in patients with
      focal epilepsy were identified from the literature. Retention calculation methods
      were reviewed, and published AED retention rates qualitatively compared with
      corresponding data for brivaracetam (BRV), a synaptic vesicle protein 2A ligand.
      The search identified 40 publications (corresponding to 17 studies of nine AEDs:
      eslicarbazepine, gabapentin, lacosamide, levetiracetam, oxcarbazepine,
      perampanel, pregabalin, topiramate and zonisamide) meeting eligibility criteria
      for inclusion in the review. Three methodologies to estimate retention rate were
      identified, which differed in whether patients randomised to placebo in the
      preceding randomised controlled trials (RCTs) were included or analysed
      separately, and whether retention was measured from the start of the OLE or of
      active treatment exposure. The most robust, conservative approach included all
      patients and measured retention from start of active treatment exposure, whether
      during the blinded RCT or at the start of the OLE (placebo RCT patients). Data
      using this method was available for five AEDs in this review, including BRV. The
      corresponding BRV 52week retention rate (modal doses 50-200mg/day; therapeutic
      range) was 69.8% (63.3-66.7% for other AEDs at this time point). No statistical
      indirect comparison was performed, as study populations were clinically
      heterogeneous. To avoid inconsistencies in methodologies, and allow comparison
      between AEDs when OLE data are the only long-term data available, retention rate
      analyses would benefit from the development of consistent reporting standards and
      guidelines.

PMID- 29073579
TI  - Removal of organic micropollutants in waste stabilisation ponds: A review.
AB  - As climate change and water scarcity continue to be of concern, reuse of treated
      wastewater is an important water management strategy in many parts of the world,
      particularly in developing countries and remote communities. Many countries,
      especially in remote regional areas, use waste stabilisation ponds (WSPs) to
      treat domestic wastewater for a variety of end uses, including using the treated
      wastewater for irrigation of public spaces (e.g. parks and ovals) or for crop
      irrigation. Thus, it is vital that the resulting effluent meets the required
      quality for beneficial reuse. In this paper, both the performance of WSPs in the
      removal of organic micropollutants, and the mechanisms of removal, are reviewed.
      The performance of WSPs in the removal of organic micropollutants was found to be
      highly variable and influenced by many factors, such as the type and
      configuration of the ponds, the operational parameters of the treatment plant,
      the wastewater quality, environmental factors (e.g. sunlight, temperature, redox
      conditions and pH) and the characteristics of the pollutant. The removal of
      organic micropollutants from WSPs has been attributed to biodegradation,
      photodegradation and sorption processes, the majority of which occur in the
      initial treatment stages (e.g. in the anaerobic or facultative ponds). Out of the
      many hundreds of organic micropollutants identified in wastewater, only a limited
      number (40) have been studied in WSPs, with the majority of these pollutants
      being pharmaceuticals, personal care products and endocrine disrupting compounds.
      Thus, future research on the fate of organic micropollutants in WSPs should
      encompass a broader range of micropollutants and include emerging organic
      pollutants, such as illicit drugs and perfluorinated compounds. Further research
      is also needed on the formation and toxicity of transformation products from
      organic micropollutants in WSPs, since the transformation products of some
      organic micropollutants can be more toxic than the parent compound. Combining
      other wastewater treatment processes with WSPs for removal of recalcitrant
      organic micropollutants should also be considered.

PMID- 29073580
TI  - Facile synthesis and characterisation of AlNs using Protein Rich Solution
      extracted from sewage sludge and its application for ultrasonic assisted dye
      adsorption: Isotherms, kinetics, mechanism and RSM design.
AB  - Protein Rich Solution (PRS) was prepared from the sewage sludge with ultrasonic
      assistance. With PRS, aluminium based nanosheet like materials (AlNs) were
      synthesised for the ultrasonic removal of Congo Red (CR) and Crystal Violet (CV)
      dyes. PRS was characterised by UV, EEM and NMR spectral analysis. AlNs were
      characterised by FTIR, XRD, TGA, BET, SEM, AFM, TEM and XPS analysis. The point
      of zero charge of AlNs was found to be 5.4. The BET analysis ensured that the
      average pore diameter and total pore volume of AlNs as 8.464 nm and 0.11417 cc/g
      respectively. The efficacy of AlNs for the removal of toxic dyes was tested by
      performing Response surface methodology (RSM) designed experiments. The effect of
      sonication time, dosage and initial concentration on dye removal was studied at
      an optimised pH value. Langmuir, Freundlich and Temkin isotherm models were
      examined. The maximum adsorption capacity was found to be 121.951 and 105.263
      mg/g for CR and CV respectively. The kinetic models like pseudo-first order,
      pseudo-second order, Elovich and intra-particle diffusion were examined to
      understand the mechanism behind it. The results revealed that the use of
      ultrasonication enhanced the mass transfer. The experimental studies on the
      influence of ultrasound power indicated a positive relation with the removal
      efficiency. The results of thermodynamic study revealed that the process was
      spontaneous and exothermic for both the dyes. The increase in ionic strength
      increased the removal efficiency for both CR and CV. RSM predicted the optimum
      adsorbent dosages as 0.16 g for 50 mg/L of CR and 0.12 g for 100 mg/L of CV dye
      solutions. The values of half-life and fractional adsorption for both CR and CV
      suggested that the low cost AlNs has high potential to remove the toxic
      industrial dyes.

PMID- 29073581
TI  - Effective strategies for anode surface modification for power harvesting and
      industrial wastewater treatment using microbial fuel cells.
AB  - This study investigates three different strategies for anode surface treatment by
      doping superficial nitrogen groups on the anode surfaces of carbon cloth (CC) and
      carbon paper (CP). The chosen anodes were hydrothermally treated in the presence
      of an ammonia solution (AST), a mixture of nitric acid and sulfuric acid (AHT),
      and solid urea (UT) at 180  degrees C for 3 h. The utilized characterization
      techniques confirmed doping of nitrogen on the anode surfaces and a decrease in
      the oxygen-bonded carbon content. Furthermore, the results showed that the power
      and current densities were significantly affected by the surface modification
      techniques. Interestingly, the AST strategy achieved the highest power density of
      159.3 mW-2 and 91.6 mWm-2, which revealed an increase in power of 115% and 56.8%
      for CC-AST and CP-AST, respectively. Additionally, the maximum coulombic
      efficiencies were 63.9% and 27.5% for the CC-AST and CP-AST anodes, respectively.
      Overall, these results highlight the significance of anode surface modification
      for enhancing MFC performance to generate electricity and treat actual
      wastewater.

PMID- 29073582
TI  - Elderly patients with gastrointestinal stromal tumour (GIST) receive less
      treatment irrespective of performance score or comorbidity - A retrospective
      multicentre study in a large cohort of GIST patients.
AB  - OBJECTIVE: Although gastrointestinal stromal tumours (GIST) predominantly occur
      in older patients, data on treatment patterns in elderly GIST patients are
      scarce. METHODS: Patients registered in the Dutch GIST Registry (DGR) from
      January 2009 until December 2016 were included. Differences in treatment patterns
      between elderly (>=75 years) and younger patients were compared. Multivariate
      analyses were conducted using logistic regression. RESULTS: Data of 145 elderly
      and 665 non-elderly patients were registered (median age 78 and 60 years
      respectively). In elderly patients, performance score (WHO-PS) and age-adjusted
      Charlson comorbidity index (ACCI) were significantly higher (p < 0.05; p <
      0.001), and albumin level significantly lower (p = 0.04). Hundred-and-nine
      (75.2%) elderly and 503 (75.6%) non-elderly patients had only localised disease.
      Surgery was performed in 57% of elderly versus 84% of non-elderly patients (p =
      0.003, OR: 0.26, 95% CI: 0.11-0.63). No differences in surgery outcome or
      complications were found. Thirty-eight percent of elderly with an indication for
      adjuvant treatment did receive imatinib versus 68% of non-elderly (p = 0.04, OR:
      0.47, 95% CI: 0.23-0.95). Thirty-six elderly and 162 non-elderly patients had
      metastatic disease. Palliative imatinib was equally given (mean dose 400 mg) and
      adverse events were mostly minor (p = 0.71). In elderly, drug-related toxicity
      was in 32.7% reason to discontinue imatinib versus 5.1% in non-elderly (p =
      0.001, OR 13.5, 95% CI: 2.8-65.0). Median progression-free survival (PFS) was 24
      months in elderly and 33 months in non-elderly (p = 0.10). Median overall
      survival (OS) was 34 months and 59 months respectively (p = 0.01). CONCLUSIONS:
      Elderly GIST patients with localised disease receive less surgery and adjuvant
      treatment, irrespective of comorbidity and performance score. Drug-related
      toxicity results more often in treatment discontinuation. This possibly results
      in poor outcome.

PMID- 29073583
TI  - Divergent oestrogen receptor-specific breast cancer trends in Ireland (2004
      2013): Amassing data from independent Western populations provide etiologic
      clues.
AB  - The aetiology and clinical behaviour of breast cancers vary by oestrogen receptor
      (ER) expression, HER2 expression and over time. Data from the United States and
      Denmark show rising incidence rates for ER+ and falling incidence rates for ER-
      breast cancers. Given that Ireland is a somewhat similar Western population but
      with distinctive risk exposures (especially for lactation), we analysed breast
      cancer trends by ER status; and for the first time, by the joint expression of
      ER+/-/HER2+/-. We assessed invasive breast cancers (n = 24,845; 2004-2013) within
      the population-based National Cancer Registry of Ireland. The population at risk
      was obtained from the Irish Central Statistics Office (n = 10,401,986). After
      accounting for missing ER and HER2 data, we assessed receptor-specific secular
      trends in age-standardised incidence rates (ASRs) with the estimated annual
      percentage change (EAPC) and corresponding 95% confidence intervals (95% CI). Age
      period-cohort models were also fitted to further characterise trends accounting
      for age, calendar-period and birth-cohort interactions. ASRs increased for ER+
      (EAPC: 2.2% per year [95% CI: 0.97, 3.45%/year]) and decreased for ER- cancers
      (EAPC: -3.43% per year [95% CI: -5.05, -1.78%/year]), as well as for specific age
      groups at diagnosis (<30-49, 50-64 and >=65 years). ER+/HER2- cancers rose,
      ER+/HER2+ cancers were statistically flat and ER-/HER+/- cancers declined.
      Secular trends for ER+/- cancers in Ireland were like those previously observed.
      Stratification by HER2+/- expression did not substantively alter ER+/- trends.
      The divergence of ER+/- incidence rates among independent Western populations
      likely reflects calendar-period and/or risk factor changes with differential
      effects for ER+ and ER- breast cancers.

PMID- 29073586
TI  - New psychoactive substances: Can there be any effective legal enforcement?

PMID- 29073584
TI  - Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of
      STEVIE, an international, open-label trial.
AB  - BACKGROUND: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov,
      NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class
      Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell
      carcinoma (BCC)-in a patient population representative of clinical practice.
      Primary analysis data are presented. PATIENTS AND METHODS: Patients with locally
      advanced or metastatic BCC received oral vismodegib 150 mg/d until progressive
      disease, unacceptable toxicity, or withdrawal. Primary objective was safety.
      Efficacy variables were assessed as secondary end-points. RESULTS: Evaluable
      adult patients (N = 1215, 1119 locally advanced; 96 metastatic BCC) from 36
      countries were treated; 147 patients (12%) remained on study at time of
      reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients
      (98%) had >=1 treatment-emergent adverse event (TEAE). The incidence of the most
      common TEAEs was consistent with reports in previous analyses. No association
      between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed.
      Serious TEAEs occurred in 289 patients (23.8%). Exposure >=12 months did not lead
      to increased incidence or severity of new TEAEs. The majority of the most common
      TEAEs ongoing at time of treatment discontinuation resolved by 12 months
      afterwards, regardless of Gorlin syndrome status. Response rates (investigator
      assessed) in patients with histologically confirmed measurable baseline disease
      were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally
      advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC.
      CONCLUSIONS: The primary analysis of STEVIE demonstrates that vismodegib is
      tolerable in typical patients in clinical practice; safety profile is consistent
      with that in previous reports. Long-term exposure was not associated with
      worsening severity/frequency of TEAEs. Investigator-assessed response rates
      showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665.

PMID- 29073585
TI  - Evaluation of phenytoin serum levels following a loading dose in the acute
      hospital setting.
AB  - PURPOSE: Due to the complex pharmacokinetic profiles of phenytoin (PHT) and
      fosphenytoin (FOS), achieving sustained, targeted serum PHT levels in the first
      day of use is challenging. METHODS: A population based approach was used to
      analyze total serum PHT (tPHT) level within 2-24h of PHT/FOS loading with or
      without supplementary maintenance or additional loading doses among PHT-naive
      patients in the acute hospital setting. Adequate tPHT serum level was defined as
      >=20MUg/mL. RESULTS: Among 494 patients with 545 tPHT serum levels obtained in
      the first 2-24h after the loading dose (LD), tPHT serum levels of either
      <or>=20MUg/mL were observed along wide and overlapping cumulative dose ranges.
      Among those receiving 15-20mg/kg and 20-55mg/kg weight-based loading dose, 63%
      and 51% respectively did not attain tPHT serum level of >=20MUg/mL even within
      the first 6h of treatment. For the 393 available concomitant free and total serum
      PHT levels, correlation was weak, r=0.36. CONCLUSION: Close laboratory
      surveillance and PHT/FOS dose adjustments are recommended to ensure adequate and
      sustained tPHT serum levels early in treatment. Free serum PHT level is the
      preferred method of drug monitoring.

PMID- 29073587
TI  - Are animal models applicable for research on schizophrenia?

PMID- 29073588
TI  - Allele Drop Out Conferred by a Frequent CYP2D6 Genetic Variation For Commonly
      Used CYP2D6*3 Genotyping Assays.
AB  - BACKGROUND/AIM: Accurate genotyping of CYP2D6 is challenging due to its inherent
      genetic variation, copy number variation (duplications and deletions) and hybrid
      formation with highly homologous pseudogenes. Because a relatively high
      percentage (~25%) of clinically prescribed drugs are substrates for this enzyme,
      accurate determination of its genotype for phenotype prediction is essential.
      METHODS: A cohort of 365 patient samples was genotyped for CYP2D6 using Sanger
      sequencing (as the gold standard), hydrolysis probe assays or pyrosequencing.
      RESULTS: A discrepant result between the three genotyping methods for the loss of
      function CYP2D6*3 (g.2549delA, rs35742686) genetic variant was found in one of
      the samples. This sample also contained the CYP2D6 g.2470T>C (rs17002852)
      variation, which had an allele frequency of 2.47% in our cohort. Redesign of the
      CYP2D6*3 pyrosequencing and hydrolysis probe assays to avoid CYP2D6 g.2470
      corrected the anomaly. CONCLUSION: To evidence allele drop out and increase the
      accuracy of genotyping, intra-patient validation of the same genetic variation
      with at least two separate methods should be considered.

PMID- 29073589
TI  - Effect of Unshaven Hair with Absorbable Sutures and Early Postoperative Shampoo
      on Cranial Surgery Site Infection.
AB  - BACKGROUND: Cranial surgical site infection is a significant cause of morbidity
      and mortality in hospitals. Preoperative hair shaving for cranial neurosurgical
      procedures is performed traditionally in an attempt to protect patients against
      complications from infections at cranial surgical sites. However, preoperative
      shaving of surgical incision sites using traditional surgical blades without
      properly washing the head after surgery can cause infections at surgical sites.
      Therefore, a rapid protocol in which the scalp remains unshaven and absorbable
      sutures are used for scalp closure with early postoperative shampooing is
      examined in this study. METHODS: A retrospective comparative study was conducted
      from January 2008 to December 2012. A total of 2,641 patients who underwent
      unshaven cranial surgery with absorbable sutures for scalp closure were enrolled
      in this study. Data of 1,882 patients who underwent surgery with the traditional
      protocol from January 2005 to December 2007 were also analyzed for comparison.
      RESULTS: Of 2,641 patients who underwent cranial surgery with the rapid protocol,
      all but 2 (0.07%) patients experienced satisfactory wound healing. Of 1,882
      patients who underwent cranial surgery with the traditional protocol, 3 patients
      (0.15%) had infections. Each infection occurred at the superficial incisional
      surgical site. CONCLUSION: Unshaven cranial surgery using absorbable sutures for
      scalp closure with early postoperative shampooing is safe and effective in the
      cranial neurosurgery setting. This protocol has a positive psychological effect.
      It can help patients accept neurosurgical procedures and improve their self-image
      after the operation.

PMID- 29073590
TI  - Temporal Associations between Fatigue, Depression, and Apathy after Stroke:
      Results of the Cognition and Affect after Stroke, a Prospective Evaluation of
      Risks Study.
AB  - BACKGROUND: Poststroke fatigue (PSF) is a form of pathological fatigue that can
      develop after stroke and has a negative impact on functional outcome. PSF is
      associated with poststroke depression (PSD), which in turn shows similarities
      with poststroke apathy (PSA). This study aimed at disentangling the temporal
      associations between PSF and PSD and between PSF and PSA. METHODS: A total of 250
      stroke patients were included, of which 243 completed the Fatigue Severity Scale,
      Montgomery-Asberg Depression Rating Scale, and Apathy Evaluation Scale at 3
      months poststroke, with follow-up measurements at 6 and 12 months after initial
      testing. Linear mixed models and linear regressions were performed to evaluate
      the temporal associations between PSF and PSD, and between PSF and PSA. RESULTS:
      PSF was present in 119 patients (49%), of whom 62 patients also had PSD (26%),
      and 21 patients (9%) also had PSA. At baseline, PSF patients showed higher
      depression levels, which remained stable at follow-up. PSD patients had higher
      fatigue levels compared with no-PSD patients at baseline, which remained stable
      at follow-up. No association between apathy and fatigue was found at baseline and
      no interaction with time was found. Change in fatigue from baseline to 12-month
      follow-up was associated with change in depression and with change in apathy.
      CONCLUSIONS: Bidirectional associations were found between PSF and PSD. In
      treatment and rehabilitation programs, early focus on the presence of PSD and PSF
      is important, since these conditions tend to persist. As there are currently more
      treatment options for PSD, attention for PSD is important and might also have a
      beneficial effect on PSF.

PMID- 29073591
TI  - Targeted Resequencing of Putative Growth-Related Genes Using Whole Exome
      Sequencing in Patients with Severe Primary IGF-I Deficiency.
AB  - BACKGROUND/AIMS: To elucidate the genetic causes of severe primary insulin-like
      growth factor-I deficiency (SPIGFD) by systematic, targeted, next-generation
      sequencing (NGS)-based resequencing of growth-related genes. METHODS: Clinical
      phenotyping followed by NGS in 17 families including 6 affected sib pairs.
      RESULTS: We identified disease-causing, heterozygous, de novo variants in HRAS
      (p.Gly13Cys) and FAM111A (p.Arg569His) in 2 male patients with syndromic SPIGFD.
      A previously described homozygous GHR nonsense variant was detected in 2 siblings
      of a consanguineous family (p.Glu198*). Furthermore, we identified an inherited
      novel variant in the IGF2 gene (p.Arg156Cys) of a maternally imprinted gene in a
      less severely affected father and his affected daughter. We detected 2 other
      novel missense variants in SH2B1 and SOCS2, both were inherited from an
      unaffected parent. CONCLUSIONS: Screening of growth-related genes using NGS
      based, large-scale, targeted resequencing identified disease-causing variants in
      HRAS, FAM111A, and GHR. Considering the increased risk of subjects with HRAS
      mutations for neoplasms, close clinical monitoring and a thorough discussion of
      the risk/benefit ratio of the treatment with recombinant IGF-I is mandatory.
      Segregation analysis proved to be critical in the interpretation of potential
      SPIGFD-associated gene variations.

PMID- 29073593
TI  - [Erfahrungen am Lebensende: Eine Umfrage bei Arzten und Pflegenden eines Spitals
      fur anthroposophisch erweiterte Medizin].

PMID- 29073592
TI  - Dronabinol Is a Safe Long-Term Treatment Option for Neuropathic Pain Patients.
AB  - Treatment of neuropathic pain (NP) symptoms associated with multiple sclerosis
      (MS) is frequently insufficient. Yet, cannabis is still rarely offered for
      treatment of pain. This clinical trial aimed at showing the positive benefit-risk
      ratio of dronabinol. Two hundred forty MS patients with central NP entered a 16
      weeks placebo-controlled phase-III study followed by a 32-weeks open-label
      period. One hundred patients continued therapy for overall up to 119 weeks.
      Primary endpoint was change of pain intensity on the 11-point Numerical Rating
      Scale over a 16-weeks treatment period. Safety was assessed on the basis of
      adverse reactions (ARs), signs of dependency and abuse. Pain intensity during 16
      weeks dronabinol and placebo treatment was reduced by 1.92 and 1.81 points
      without significant difference in between (p = 0.676). Although the proportion of
      patients with ARs was higher under dronabinol compared to placebo (50.0 vs.
      25.9%), it decreased during long-term use of dronabinol (26%). No signs of drug
      abuse and only one possible case of dependency occurred. The trial results
      demonstrate that dronabinol is a safe long-term treatment option.

PMID- 29073594
TI  - Gaining an Accurate Diagnosis: A Multidisciplinary Approach.

PMID- 29073595
TI  - Epigenetically-Regulated MicroRNA-9-5p Suppresses the Activation of Hepatic
      Stellate Cells via TGFBR1 and TGFBR2.
AB  - BACKGROUND/AIMS: Recently, microRNAs (miRNAs) have been demonstrated to act as
      regulators of activation of hepatic stellate cells (HSCs). It is well known that
      the main profibrogenic inducer transforming growth factor-beta1 (TGF-beta1)
      contributes to HSC activation, which is a key event in liver fibrosis. Increasing
      studies show that miR-9-5p is down-regulated in liver fibrosis and restoration of
      miR-9-5p limits HSC activation. However, the role of miR-9-5p in TGF-beta1
      induced HSC activation is still not clear. METHODS: miR-9-5p expression was
      quantified using real-time PCR in chronic hepatitis B (CHB) patients and TGF
      beta1-treated LX-2 cells. In CHB patients, histological activity index (HAI) and
      fibrosis stages were assessed using the Ishak scoring system. Effects of miR-9-5p
      on liver fibrosis in vivo and in vitro were analyzed. Luciferase activity assays
      were performed to examine the binding of miR-9-5p to the 3'-untranslated region
      of type I TGF-beta receptor (TGFBR1) as well as TGFBR2. RESULTS: Compared with
      healthy controls, miR-9-5p was reduced in CHB patients. There was a lower miR-9
      5p expression in CHB patients with higher fibrosis scores or HAI scores. miR-9-5p
      was down-regulated by TGF-beta1 in a dose-dependent manner. TGF-beta1-induced HSC
      activation including cell proliferation, alpha-SMA and collagen expression was
      blocked down by miR-9-5p. Notably, miR-9-5p ameliorates carbon tetrachloride
      induced liver fibrosis. As determined by luciferase activity assays, TGFBR1 and
      TGFBR2 were targets of miR-9-5p. Further studies demonstrated that miR-9-5p
      inhibited TGF-beta1/Smads pathway via TGFBR1 and TGFBR2. Interestingly, promoter
      methylation was responsible for miR-9-5p down-regulation in liver fibrosis. The
      relationship between miR-9-5p expression and methylation was confirmed in CHB
      patients and TGF-beta1-treated cells. CONCLUSION: Our results demonstrate that
      miR-9-5p could inhibit TGF-beta1-induced HSC activation through TGFBR1 and
      TGFBR2. Loss of miR-9-5p is associated with its methylation status in liver
      fibrosis.

PMID- 29073596
TI  - Efficacy of Antenatal Corticosteroid Treatment on Neurodevelopmental Outcome
      according to Head Circumference at Birth.
AB  - BACKGROUND: There are concerns about the efficacy of antenatal corticosteroid
      treatment (ACT) in the growth-restricted fetus. OBJECTIVE: To evaluate the effect
      of ACT on neurodevelopmental outcome at 2 years of corrected age according to the
      z score of birth head circumference (ZS HC) in a large prospective cohort of
      preterm infants. METHODS: This study was conducted as a population-based,
      prospective, multicenter study, including 4,965 infants born between 24 and 33
      weeks' gestation and whose status regarding ACT and the measurement of head
      circumference at birth were available. They were evaluated at 2 years of
      corrected age to assess neurological outcome. Three approaches were considered to
      estimate the effect of ACT on neurodevelopment: (i) logistic regression with
      adjustment on propensity score, (ii) weighted logistic regression using the
      inverse probability of treatment weighting method, and (iii) 1:1 matching of
      gestational age, ZS HC, and propensity score between treated and nontreated
      infants. RESULTS: ACT was documented in 60% of infants. Three groups of infants
      were considered according to their ZS HC: between -3 and -1 standard deviation
      (SD), -1 and +1 SD, and +1 and +3 SD, respectively. ACT was associated with a
      significant improvement of neurodevelopmental outcome only for infants with an ZS
      HC of between +1 and +3 SD (adjusted OR 1.72; 95% CI 1.06-2.79). Moreover, ORs
      estimated in the -3 to -1 and +1 to +3 categories were significantly different.
      CONCLUSION: We found beneficial effects of ACT on neurodevelopmental outcomes at
      2 years of corrected age only in preterm infants with a ZS HC >1 SD.

PMID- 29073597
TI  - Treatment of Enterococcal Peritonitis in Peritoneal Dialysis Patients by Oral
      Amoxicillin or Intra-Peritoneal Vancomcyin: a Retrospective Study.
AB  - BACKGROUND/AIMS: Enterococcal peritonitis in peritoneal dialysis (PD) patients is
      associated with a high complication rate. The optimal treatment regimen of PD
      related enterococcal peritonitis is controversial. The latest international
      guideline recommends intra-peritoneal (IP) vancomycin. Although ampicillin is
      often effective for systemic enterococcal infections, they have little in vitro
      activity when added to common PD solutions. Since oral amoxicillin achieves
      therapeutic drug level in the peritoneal cavity, we explore the efficacy of oral
      amoxicillin for enterococcal peritonitis. METHODS: We studied 105 episodes of
      enterococcal peritonitis over 20 years in our unit; 43 (41.0%) were treated with
      oral amoxicillin, and 62 (59.0%) with IP vancomycin. Their clinical outcome was
      reviewed. RESULT: The overall primary response rate to oral amoxicillin and IP
      vancomycin was 76.4% and 85.5%, respectively (p = 0.3). The complete cure rate of
      oral amoxicillin and IP vancomycin was 55.8% and 54.8%, respectively (p = 0.8).
      When the 5 episodes of ampicillin-resistant Enterococcus episodes were excluded,
      the primary response rate and complete cure rate of oral amoxicillin were 86.8%
      and 63.2%, respectively. CONCLUSION: Oral amoxicillin has an excellent primary
      response rate and complete cure rate for PD-related peritonitis episodes caused
      by Enterococcus species, indicating that oral amoxicillin is a valid and
      convenient therapeutic option for enterococcal peritonitis episodes.

PMID- 29073598
TI  - Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a
      Bioluminescence Mouse Model.
AB  - BACKGROUND: Liver regeneration requires the formation of new blood vessels.
      Endothelial cell proliferation is stimulated by vascular endothelial growth
      factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was
      to investigate VEGFR-2 expression in vivo during liver regeneration after partial
      hepatectomy (PHx). METHODS: Transgenic VEGFR-2-luc mice were used in which the
      luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3
      PHx, the mice underwent in vivo bioluminescence imaging until the 14th
      postoperative day. Additionally, liver tissue was analyzed by
      immunohistochemistry, in vitro luminescence assays, and quantitative RT-PCR.
      RESULTS: In vivo bioluminescence imaging showed a significant increase in VEGFR-2
      promoter activity after PHx. Maximum signal was recorded on the 3rd day; 8 days
      postoperatively the signal intensity decreased significantly. On the 14th day,
      bioluminescence signal reached almost baseline levels. Immunohistochemistry,
      quantitative RT-PCR, and in vitro luminescence confirmed a significant increase
      on the 3rd day following resection. The mRNA expression of VEGFR-2 was
      significantly higher on day 3 than preoperatively as well as on day 8.
      CONCLUSION: In vivo bioluminescence imaging with transgenic VEGFR-2-luc mice is
      feasible and provides a convenient model for noninvasively studying VEGFR-2
      expression during liver regeneration. This may facilitate further experiments
      with modulation of angiogenesis by different substances.

PMID- 29073599
TI  - Combination of Solamargine and Metformin Strengthens IGFBP1 Gene Expression
      Through Inactivation of Stat3 and Reciprocal Interaction Between FOXO3a and SP1.
AB  - BACKGROUND/AIMS: Solamargine, one natural photochemical component from
      traditional plants, has been shown to have anti-cancers properties. We previously
      showed that solamargine inhibited the growth of non-small-cell lung cancer
      (NSCLC) cells through suppression of prostaglandin E2 (PGE2) receptor EP4 gene
      and regulation of downstream signaling pathways. However, the detailed mechanism
      underlying this, especially in combination of metformin, a known AMPK activator,
      still remained to be determined. METHODS: Cell viability was measured using a 3
      (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and
      colorimetric 5-bromo-2-deoxyuridine (BrdU) ELISA methods, respectively. Western
      blot analysis and immunohistochemistry were performed to examine the
      phosphorylation and protein expressions of signal transducer and activator of
      transcription 3 (Stat3), SP1, forkhead box O3a (FOXO3a), and insulin-like growth
      factor (IGF)-IGF binding protein 1 (IGFBP1). The expression of IGFBP1 mRNA was
      measured by quantitative real time PCR (qRT-PCR). Silencing of FOXO3a and IGFBP1
      were examined by siRNA procedures. Exogenously expression of SP1, FOXO3a, and
      IGFBP1 were carried out by transient transfection assays. The promoter activity
      of IGFBP1 was tested using Secrete-PairTM Dual Luminescence Assay Kit. A
      xenografted tumor model was used to further test the effect of solamargine in
      combining with metformin in vivo. RESULTS: We further demonstrated that
      solamargine inhibited growth and induced cell cycle arrest in other NSCLC cell
      lines. Through mechanism-based approaches, we showed that solamargine decreased
      the phosphorylation of Stat3; In addition, solamargine induced FOXO3a, whereas
      reduced SP1 protein levels; all of which were abrogated in cells with
      overexpressed Stat3 gene. Interestingly, there is interaction between FOXO3a and
      SP1. Moreover, solamargine increased mRNA, protein expression and promoter
      activity of IGFBP1, which was not observed in cells with overexpressed SP1 or
      with silenced FOXO3a genes. Finally, ablation of IGFBP1 expression by siRNA
      blocked the effect of solamargine on cell growth inhibition. More importantly,
      there was a synergy of combination of solamargine and metformin. Similar findings
      were also observed in vivo. CONCLUSION: Our results show that solamargine
      increases IGFBP1 gene expression through inactivation of Stat3, followed by
      regulation and reciprocal interaction of FOXO3a and SP1 in vitro and in vivo.
      This ultimately leads to suppression of human lung cancer cell growth. Moreover,
      this is a synergy of solamargine in combination with metformin in this process.
      This study unravels a novel mechanism underlying the anti-lung cancer effects of
      solamargine in combination of metformin, and suggests a potential new lung cancer
      associated therapy.

PMID- 29073600
TI  - New Insight into Affectivity in Schizophrenia: from the Phenomenology of Marc
      Richir.
AB  - BACKGROUND: According to Karl Jaspers, psychopathology requires a comprehensive
      method, understood as a systematic exploration of the first-person perspective of
      the patient's experience. At the same time, however, schizophrenia for Jaspers is
      characterized by its radical incomprehensibility. In addition, Rumke's so-called
      "praecox feeling" paradoxically combines the incomprehensibility of schizophrenic
      experience and the evidence of its pathological manifestation in the encounter.
      AIM: Through a re-examination of the notions of affectivity and interaffective
      contact we propose a coherent theoretical model to explain the clinician's
      paradoxical understanding of schizophrenia. METHOD: Phenomenological tradition
      regards affectivity as an encompassing phenomenon that connects body, self,
      world, and others. In our view, only a thorough and systematic link between
      corporeity and affectivity is able to explain embodied affective resonance as a
      basis of empathic comprehension. By drawing on the phenomenology of Marc Richir,
      we will systematically unfold the complex nature of affectivity and lead it back
      to a twofold constitution of corporeality. CONCLUSION: The Richirian account on
      affectivity can be fruitfully put into discussion with other recent
      phenomenological models on schizophrenia. It might be able to exhibit affectivity
      as the operative ground of minimal self-disturbance and thus argue for its
      intersubjective dimension.

PMID- 29073601
TI  - Early Continuous Veno-Venous Hemofiltration Is Effective in Decreasing Intra
      Abdominal Pressure and Serum Interleukin-8 Level in Severe Acute Pancreatitis
      Patients with Abdominal Compartment Syndrome.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of early continuous
      veno-venous hemofiltration (CVVH) in decreasing the intra-abdominal pressure
      (IAP) and serum interleukin-8 (IL-8) level in severe acute pancreatitis (SAP)
      patients with abdominal compartment syndrome (ACS). METHODS: Twenty-five ACS
      patients of SAP were enrolled in a prospective study conducted according to the
      standard management protocol. They were treated in the intensive care unit (ICU)
      of Affiliated Yidu Central Hospital of Weifang Medical College and underwent
      CVVH. Eleven patients were set up as the control group that received no
      hemofiltration and surgical treatment due to economic or other reasons but solely
      conventional treatment. Serum amylase, liver and kidney function, and C reactive
      protein were investigated before and after treatment. IAP and blood level of IL-8
      were measured daily to investigate their time course of changes and the
      correlation between the 2 parameters. RESULTS: Serum amylase levels, C-reactive
      protein and IAP were significantly lower and liver and kidney function was
      significantly better than those of the control group (p < 0.05). IAP on admission
      to the ICU was high, at 22.9 +/- 2.1 mm Hg. The IAP was significantly lower to
      17.2 +/- 2.2 mm Hg (p < 0.01) 24 h after the initiation of CVVH, and thereafter
      decreased rapidly. The average blood level of IL-8 was high at 88.2 +/- 25.1 ng/L
      on admission. However, it significantly decreased to 63.2 +/- 18.7 ng/L (p <
      0.01) 24 h after the initiation of CVVH, and subsequently decreased. There was a
      significant positive correlation between the blood level of IL-8 and IAP(r =
      0.62, p < 0.01). CONCLUSIONS: CVVH is effective to decrease the IAP and the blood
      level of IL-8 in ACS patients of SAP. The blood level of IL-8 was significantly
      correlated with IAP, suggesting that IL-8 might play an important role in the
      pathogenesis of ACS. Early CVVH appeared to be effective in the treatment of ACS
      in patients with SAP through the removal of causative cytokines such as IL-8, and
      it thereby decreased interstitial edema to lower IAP and should be applied in the
      early stage of ACS. Video Journal Club 'Cappuccino with Claudio Ronco' at
      http://www.karger.com/?doi=480223.

PMID- 29073602
TI  - Current Perspectives in Kidney Diseases.

PMID- 29073603
TI  - Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump
      Coronary Surgery.
AB  - BACKGROUND: Cardiac surgery often causes ischemia and development of a systemic
      inflammatory response syndrome, which impairs vascular barrier function, normally
      maintained by the endothelial cell line and the endothelial glycocalyx (EG). The
      EG normally covers and protects healthy endothelial cells throughout the
      vasculature. The aim of the present study was to assess the disruption of the
      cellular part of the microvascular barrier by determining parameters of
      endothelial cell activation known to influence and reflect cell-cell junctional
      integrity. Particular attention was placed on angiopoietins and their important
      effects on endothelial gap junctions. Furthermore, comparative measurements were
      undertaken in patients undergoing on- and off-pump cardiac surgery, the latter
      group presumably experiencing less ischemic stress. METHODS: 30 patients
      undergoing elective coronary artery bypass surgery were assigned to the
      conventional coronary artery bypass (CCAB) group (n = 15) or the off-pump
      coronary artery bypass grafting (OPCAB) group (n = 15). Blood samples were
      obtained for measuring angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular
      endothelial (VE)-cadherin, and endocan at various time points. RESULTS: There
      were significant increases in all measured parameters in both study groups versus
      the respective basal values. Maximal increases were as follows: Ang-1: CCAB
      +220%, OPCAB +166%, p < 0.05 each; Ang-2: CCAB +150%, OPCAB +20%, p < 0.05 each;
      VE-cadherin: CCAB +87%, OPCAB +66%, p < 0.05 each; endocan: CCAB +323%, OPCAB
      +72%, p < 0.05 each. CONCLUSION: The present study demonstrates the activation of
      endothelial cells, shedding of cell-cell contacts and a potential intrinsic
      counterregulation by Ang-1 and endocan in patients undergoing major cardiac
      surgery. Quantitatively greater deviations of parameters in the CCAB than in the
      OPCAB group suggest a relation between the occurrence of ischemia/reperfusion and
      the extent of endothelial activation.

PMID- 29073604
TI  - Cardiac Mesenchymal Stem Cells Proliferate Early in the Ischemic Heart.
AB  - BACKGROUND/PURPOSE: Cardiac mesenchymal stem cells (MSCs) could stimulate cell
      specific regenerative mechanisms after myocardial infarction (MI) depending on
      spatial origin, distribution, and niche regulation. We aimed at identifying and
      isolating tissue-specific cardiac MSCs that could contribute to regeneration.
      METHODS: Following permanent ligation of the left anterior descending coronary
      artery in rats (n = 16), early cardiac tissues and cardiac mononuclear cells
      (MNCs) were analyzed by immunohistology, confocal laser scanning microscopy, and
      flow cytometry, respectively. Early postischemic specific MSCs were purified by
      fluorescence-activated cell sorting, cultivated under standardized culture
      conditions, and tested for multipotent differentiation in functional
      identification kits. RESULTS: Cardiac MSC niches were detected intramyocardially
      in cell clusters after MI and characterized by positive expression for vimentin,
      CD29, CD44, CD90, CD105, PDGFRalpha, and DDR2. Following myocardial ischemia,
      proliferation was induced early and proliferation density was approximately 11%
      in intramyocardial MSC clusters of the peri-infarction border zone. Cluster sizes
      increased by 157 and 64% in the peri-infarction and noninfarcted areas of
      infarcted hearts compared with noninfarcted hearts 24 h following MI,
      respectively. Coincidentally, flow cytometry analyses illustrated postischemic
      moderate enrichments of CD45-CD44+ and CD45-DDR2+ cardiac MNCs. We enabled
      isolation of early postischemic culturable cardiac CD45-CD44+DDR2+ MSCs that
      demonstrated typical clonogenicity with colony-forming unit-fibroblast formation
      as well as adipogenic, chondrogenic, and osteogenic differentiation. CONCLUSIONS:
      MI triggered early proliferation in specific cardiac MSC niches that were
      organized in intramyocardial clusters. Following targeted isolation, early
      postischemic cardiac CD45-CD44+DDR2+ MSCs exhibited typical characteristics with
      multipotent differentiation capacity and clonogenic expansion.

PMID- 29073605
TI  - N-Cadherin Maintains the Healthy Biology of Nucleus Pulposus Cells under High
      Magnitude Compression.
AB  - BACKGROUND/AIMS: Mechanical load can regulate disc nucleus pulposus (NP) biology
      in terms of cell viability, matrix homeostasis and cell phenotype. N-cadherin (N
      CDH) is a molecular marker of NP cells. This study investigated the role of N-CDH
      in maintaining NP cell phenotype, NP matrix synthesis and NP cell viability under
      high-magnitude compression. METHODS: Rat NP cells seeded on scaffolds were
      perfusion-cultured using a self-developed perfusion bioreactor for 5 days. NP
      cell biology in terms of cell apoptosis, matrix biosynthesis and cell phenotype
      was studied after the cells were subjected to different compressive magnitudes
      (low- and high-magnitudes: 2% and 20% compressive deformation, respectively). Non
      loaded NP cells were used as controls. Lentivirus-mediated N-CDH overexpression
      was used to further investigate the role of N-CDH under high-magnitude
      compression. RESULTS: The 20% deformation compression condition significantly
      decreased N-CDH expression compared with the 2% deformation compression and
      control conditions. Meanwhile, 20% deformation compression increased the number
      of apoptotic NP cells, up-regulated the expression of Bax and cleaved-caspase-3
      and down-regulated the expression of Bcl-2, matrix macromolecules (aggrecan and
      collagen II) and NP cell markers (glypican-3, CAXII and keratin-19) compared with
      2% deformation compression. Additionally, N-CDH overexpression attenuated the
      effects of 20% deformation compression on NP cell biology in relation to the
      designated parameters. CONCLUSION: N-CDH helps to restore the cell viability,
      matrix biosynthesis and cellular phenotype of NP cells under high-magnitude
      compression.

PMID- 29073606
TI  - Inhibitory Effect of Afatinib on Platelet Activation and Apoptosis.
AB  - BACKGROUND/AIMS: The epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor afatinib is used for the treatment of several malignancies. Afatinib is
      at least partially effective by triggering apoptosis of tumor cells. Platelets
      may similarly undergo apoptosis, which is characterized by caspase 3 activation,
      cell shrinkage and phosphatidylserine translocation. However, an effect of
      afatinib on platelets has never been reported. The present study explored whether
      treatment of platelets with afatinib modifies platelet activation and apoptosis
      in the absence and presence of platelet activators thrombin or collagen related
      peptide (CRP). METHODS: Platelets isolated from wild-type mice were exposed for
      30 minutes to afatinib (18 ug/ml) without or with subsequent treatment with
      thrombin (0.005 U/ml or 0.01 U/ml) or CRP (2 ug/ml or 5 ug/ml). Flow cytometry
      was employed to estimate Orai1 abundance at the platelet surface with specific
      antibodies, cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet
      degranulation from P-selectin abundance, integrin activation from alphaIIbbeta3
      integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit,
      phosphatidylserine abundance from annexin-V-binding, platelet volume from forward
      scatter and aggregation utilizing staining with CD9-APC and CD9-PE. RESULTS: In
      the absence of thrombin and CRP, the administration of afatinib (18 ug/ml)
      slightly, but significantly, increased [Ca2+]i and annexin-V-binding, but did not
      significantly modify Orai1 abundance, P-selectin abundance, activated
      alphaIIbbeta3 integrin, cell volume, caspase activity and aggregation. Exposure
      of platelets to 0.005 U/ml or 0.01 U/ml thrombin or 2 ug/ml or 5 ug/ ml CRP was
      followed by a significant increase of Orai1 abundance, increase of [Ca2+]i, P
      selectin abundance, alphaIIbbeta3 integrin activity, annexin-V-binding, caspase
      activity, and aggregation, as well as a significant decrease of forward scatter,
      all effects significantly blunted (thrombin) or virtually abolished (CRP) by
      afatinib. CONCLUSIONS: Afatinib is a powerful inhibitor of platelet activation,
      platelet apoptosis and platelet aggregation.

PMID- 29073607
TI  - The Use of Complementary and Alternative Medicine by the General Population in
      the Czech Republic: A Follow-Up Study.
AB  - BACKGROUND: The prevalence of complementary and alternative medicine (CAM) ranges
      between 0.3% and 86% in most highly developed countries. In the Czech Republic,
      CAM is used by 76% of the general population. Our aim was to examine patterns in
      CAM use among a representative sample of the general population in the Czech
      Republic, for 2011 and 2014. MATERIAL AND METHODS: A cross-sectional survey was
      conducted. A sex-, age- and region-stratified sample of citizens aged 15 years
      and older was randomly selected from the 2014 voter registration lists (n =
      8,395,132). A comparative analysis of data collected in 2011 and 2014 was
      performed. RESULTS: Overall, 76.0% (N = 1,365) versus 87.0% (N = 1,565) of the
      respondents reported use of 1 or more CAM modalities during the past 30 days, in
      2011 and 2014, respectively (p < 0.001). In both years, the top 4 CAM modalities
      used were vitamins/minerals, herbal teas, massage, and relaxation. Yoga replaced
      dietary supplements excluding vitamins/minerals in the 5th position.
      Nevertheless, only herbal teas (48.0% vs. 53.0%, p = 0.002), massage (20.0% vs.
      26.0%, p < 0.001), relaxation (10.0% vs. 19.0%, p < 0.001), and yoga (3.7% vs.
      7.1%, p < 0.001) showed a significant increase in use. CONCLUSIONS: The
      prevalence of CAM use in the Czech Republic is increasing, especially among
      people who use biological, body- and mind-based CAM therapies. There is a great
      need to educate students and health care professionals about the efficacy and
      safety of CAM in order to meet the patients' demands on CAM.

PMID- 29073608
TI  - Neuropsychological Training of Attention Improves MS-Related Fatigue: Results of
      a Randomized, Placebo-Controlled, Double-Blind Pilot Study.
AB  - BACKGROUND: Attentional deficits may be pathophysiologically relevant in MS
      associated fatigue. PATIENTS AND METHODS: Thirty MS patients with fatigue and
      attentional deficits in neuropsychological testing participated in this
      randomized, placebo-controlled, double-blind trial. The intervention group (IG; n
      = 14) was treated with 10 h of computerized, specific neuropsychological training
      performing simple reaction time tasks, whereas the control group (CG; n = 16)
      also runs through computerized, but unspecific neuropsychological training using
      tasks without time components. The subjective feeling of fatigue was assessed
      with the Wurzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS)
      questionnaire, and testing of alertness was used as an objective measure at
      baseline and after the 2-week study period. RESULTS: Reaction times of alertness
      were significantly decreased in IG but not CG after 2 weeks. The subjective
      feeling of fatigue was ameliorated in both groups but more pronounced in IG.
      Effect sizes were below 0.7 for alertness and WEIMuS scores in CG but large and
      clinically meaningful in IG for both measures. CONCLUSIONS: Our pilot study
      suggests that neuropsychological training of attention may improve both measures
      of fatigue. The parallel improvement of attentional deficits and subjective
      fatigue after specific neuropsychological training support previous findings that
      fatigue may be at least partially caused by impaired intensity of attention.

PMID- 29073609
TI  - Modulation of the Proteasome Pathway by Nano-Curcumin and Curcumin in Retinal
      Pigment Epithelial Cells.
AB  - INTRODUCTION: Curcumin has multiple biological effects including the modulation
      of protein homeostasis by the ubiquitin-proteasome system. The purpose of this
      study was to assess the in vitro cytotoxic and oxidative effects of nano-curcumin
      and standard curcumin and characterize their effects on proteasome regulation in
      retinal pigment epithelial (RPE) cells. METHODS: Viability, cell cycle
      progression, and reactive oxygen species (ROS) production were determined after
      treatment with nano-curcumin or curcumin. Subsequently, the effects of nano
      curcumin and curcumin on proteasome activity and the gene and protein expression
      of proteasome subunits PA28alpha, alpha7, beta5, and beta5i were assessed.
      RESULTS: Nano-curcumin (5-100 MUM) did not show significant cytotoxicity or anti
      oxidative effects against H2O2-induced oxidative stress, whereas curcumin (>=10
      MUM) was cytotoxic and a potent inducer of ROS production. Both nano-curcumin and
      curcumin induced changes in proteasome-mediated proteolytic activity
      characterized by increased activity of the proteasome subunits beta2 and
      beta5i/beta1 and reduced activity of beta5/beta1i. Likewise, nano-curcumin and
      curcumin affected mRNA and protein levels of household and immunoproteasome
      subunits. CONCLUSIONS: Nano-curcumin is less toxic to RPE cells and less prone to
      induce ROS production than curcumin. Both nano-curcumin and curcumin increase
      proteasome-mediated proteolytic activity. These results suggest that nano
      curcumin may be regarded as a proteasome-modulating agent of limited cytotoxicity
      for RPE cells.

PMID- 29073610
TI  - An Overlooked Potentially Treatable Disorder: Idiopathic Mesenteric Panniculitis.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of mesenteric
      panniculitis (MP) and to describe its clinical characteristics, therapy, and
      outcome. SUBJECTS AND METHODS: This retrospective study was carried out among
      patients with MP based on computed tomography (CT) scans from January 2012 to
      December 2015. The CT images were reanalyzed by study radiologists to confirm the
      previous MP diagnosis. Patients were divided into 2 groups, i.e., idiopathic and
      secondary, based on the presence or absence of associated predisposing factors
      such as trauma, malignancy, autoimmune disorders, ischemia, or previous abdominal
      surgery. The clinical characteristics of the 2 groups, as well as treatments,
      were assessed. RESULTS: Among the 19,869 CT scans, 36 patients (0.18%) with MP
      were identified (i.e., 19 [53%] females and 17 [47%] males). The median age was
      54 years (range 26 - 76). Twenty-four patients (67%) were categorized into the
      idiopathic group. Malignancy was the predisposing factor in 8 (22%) of those
      patients. Furthermore, abdominal pain was the cardinal symptom observed in 22
      patients (92%) in the idiopathic group. In the idiopathic group, 15 patients
      (63%) were treated with antibiotics and 16 (67%) were treated with nonsteroidal
      anti-inflammatory drugs (NSAID). One unresponsive patient was treated with
      colchicine. Symptomatic relief was achieved in all of the treated patients.
      CONCLUSION: In this study, a symptomatic idiopathic subgroup of patients with MP
      did not have any associated disorder. The response to treatment with antibiotics
      and NSAID was effective in most of the patients. Based on these findings, anti
      inflammatory treatments beyond NSAID and surgery should be reserved for patients
      who are unresponsive to antibiotics and NSAID.

PMID- 29073611
TI  - Genomic Characterization of Chromosomal Insertions: Insights into the Mechanisms
      Underlying Chromothripsis.
AB  - Chromosomal insertions are rare structural rearrangements, and the molecular
      mechanisms underlying their origin are unknown. In this study, we used whole
      genome sequencing to analyze breakpoints and junction sequences in 4 patients
      with chromosomal insertions. Our analysis revealed that none of the 4 cases
      involved a simple insertion mediated by a 3-chromosomal breakage and rejoining
      events. The inserted fragments consisted of multiple pieces derived from a
      localized genomic region, which were shuffled and rejoined in a disorderly
      fashion with variable copy number alterations. The junctions were blunt ended or
      with short microhomologies or short microinsertions, suggesting the involvement
      of nonhomologous end-joining. In one case, analysis of the parental origin of the
      chromosomes using nucleotide variations within the insertion revealed that
      maternal chromosomal segments were inserted into the paternal chromosome. This
      patient also carried both maternal alleles, suggesting the presence of zygotic
      trisomy. These data indicate that chromosomal shattering may occur in association
      with trisomy rescue in the early postzygotic stage.

PMID- 29073612
TI  - The Relationship Between Pulse Pressure, the Estimated Glomerular Filtration
      Rate, and Urine Microalbumin/Creatinine Ratio in Korean Adults.
AB  - BACKGROUND/AIMS: Pulse pressure (PP) is a predictor of adverse outcomes in
      patients on haemodialysis. Thus, the present study was conducted to assess the
      relationship between PP, estimated glomerular filtration rate (eGFR), and urine
      microalbumin/creatinine ratio (uACR) in Korean adults. METHODS: Data of 9,409
      adults (4,206 men and 5,203 women) aged >= 20 years from the Sixth Korean
      National Health and Nutrition Examination Survey (2013-2014) were analyzed.
      RESULTS: A multivariate analysis revealed that systolic blood pressure (SBP)
      (beta = -0.170, 95% confidence interval [CI], -0.216 to -0.159), diastolic blood
      pressure (DBP) (beta = 0.088, 95% CI 0.108-0.200; p < 0.001), and PP (beta = 
      0.134, 95% CI -0.215 to -0.157) were significant factors determining eGFR. In
      contrast, SBP (beta = 0.152, 95% CI, 0.985-1.456; p < 0.001), DBP (beta = -0.062,
      95% CI -1.141 to -0.442; p < 0.001), and PP (beta = 0.118, 95% CI 0.965-1.436; p
      < 0.001) were the significant factors determining uACR. The odds ratios (ORs) of
      a high PP (PP >= 60 mmHg) with a normal group [eGFR >= 60 ml/min/1.73 m2 and uACR
      < 30 mg/g] as a reference were significant for decreased eGFR [eGFR < 60
      ml/min/1.73 m2, 1.484 (95% CI, 1.003-2.196)], elevated uACR [uACR >= 30 mg/g,
      2.592 (95% CI, 2.085-3.223)], and decreased eGFR plus elevated uACR [eGFR < 60
      ml/min/1.73 m2 and uACR >= 30 mg/g, 3.889 (95% CI, 2.519-6.004)]. CONCLUSION:
      Enhanced PP was associated with a decreased eGFR and an increase in uACR in
      Korean adults. In addition, the PP increased greatly when a decrease in eGFR and
      an increase in uACR appeared simultaneously.

PMID- 29073613
TI  - Impact of the FloTrac/VigileoTM Monitoring on Intraoperative Fluid Management and
      Outcome after Liver Resection.
AB  - BACKGROUNDS: Perioperative fluid-therapy is a still a debated issue. In hepatic
      surgery, volume load must be strictly monitored to assure both a safe
      hemodynamics and low central venous pressure (CVP) to limit the backflow
      bleeding. Retrospectively, we compared intraoperative fluid management before and
      after the adoption of a semi-invasive hemodynamic monitoring. METHODS: We
      compared patients submitted to liver resection monitored by FloTrac/VigileoTM
      (group A) vs. patients who did not (group B). We searched for differences about
      hemodynamics, fluid therapy and outcome. RESULTS: Three hundred fifty-five
      patients underwent hepatic resection due to neoplasm: group A - n = 179 and group
      B - n = 176. At the end of the resection, patients of group A showed a higher
      mean arterial pressure (MAP) than group B (74 +/- 12 vs. 49.4 +/- 8 mm Hg,
      respectively; p < 0.001). Cardiac index and stroke volume variation in group A
      were within a normal range. Fluid input was higher in group B than in group A
      (12.0 +/- 3.4 vs. 7.6 +/- 3.1 mL/kg/h, respectively; p < 0.001) and fluid balance
      was significantly different: group A -400 +/- 1,527 vs. group B 326 +/- 1,527 mL
      (p < 0.001). Group B showed a greater number of cases complicated outcomes (36
      vs. 20; p = 0.014). Considering only those subjects who were able to reach their
      hemodynamic targets (MAP >=65 mm Hg and CVP <=7 mm Hg), we found similar data.
      CONCLUSIONS: Patients who received a monitored fluid therapy experienced a safer
      outcome.

PMID- 29073614
TI  - Aberrant Expression of Long Non-Coding RNAs in Newly Diagnosed Type 2 Diabetes
      Indicates Potential Roles in Chronic Inflammation and Insulin Resistance.
AB  - BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) have emerged as key players in
      several biological processes and complex diseases. The risk of type 2 diabetes
      (T2D) is determined by a combination of environmental factors and genetic
      susceptibility. The purpose of this study was to identify aberrant lncRNAs
      involved in T2D pathogenesis. METHODS: Microarray analysis was performed using
      whole blood samples from patients newly diagnosed with T2D and healthy controls.
      Pathway and Gene Ontology (GO) analyses were utilized to annotate the target
      genes. Coding non-coding co-expression (CNC) analysis was performed to construct
      a co-expression network. RESULTS: We found 55 lncRNAs and 202 mRNAs were
      differentially expressed in the T2D group compared to the healthy control group.
      Pathway and GO analyses demonstrated that dysregulated mRNAs were mainly
      associated with immune regulation, inflammation, and insulin resistance, whereas
      CNC analysis identified 10 pairs of co-expressed lncRNA-mRNAs in our patient
      cohort (R > 0.99). Furthermore, expression of the top three upregulated lncRNAs
      in the T2D group was correlated with measures of glycometabolism (P < 0.05).
      CONCLUSION: This study identified aberrantly expressed lncRNAs and mRNAs in Han
      Chinese patients with T2D, and demonstrated that dysregulated lncRNAs may have
      roles in T2D pathogenesis through regulation of inflammation and insulin
      resistance.

PMID- 29073616
TI  - Serum 1,5-Anhydroglucitol: Risk Factor of Acute Ischemic Stroke and Transient
      Ischemic Attack in Well-Controlled Diabetes.
AB  - BACKGROUND: Serum 1,5-anhydroglucitol (1,5-AG) levels are a measure that provides
      information on daily glycemic variations. We evaluated whether 1,5-AG could be a
      possible marker of acute ischemic stroke (AIS) or transient ischemic attacks
      (TIA) in patients with diabetes mellitus (DM). METHODS: We retrospectively
      reviewed electronic medical records of 5,294 AIS/TIA patients. Of the 5,294,
      1,898 had diabetes and in 1,246, serum 1,5-AG levels were measured (group S).
      Group S was divided into 2 subgroups: hemoglobin A1c (HbA1c) <7% (S-low) and >7%
      (S-high). As controls, 394 outpatients with diabetes (group C) without AIS/TIA
      were likewise divided into subgroups, C-low and C-high according to HbA1c level.
      In each HbA1c subgroup, the association between serum 1,5-AG (>=14 vs. <14 ug/mL)
      and stroke was examined using multivariable logistic regression (MLR) with
      stepwise variable selection. In model 1, the OR and 95% CI was examined adjusted
      for age and gender. Known risk factors for stroke; hypertension, dyslipidemia,
      alcohol consumption, smoking, and estimated glomerular filtration rate were
      included in model 2. RESULTS: Overall, serum 1,5-AG levels were lower in group S
      than in group C. Serum 1,5-AG levels were low in subgroups S-high and C-high,
      showing no differences in mean values. However, mean serum 1,5-AG levels in S-low
      was statistically lower than that in C-low. MLR analysis showed that the OR for
      low (<14 ug/mL) 1,5-AG for stroke was statistically significant only in well
      controlled diabetes (OR [95% CI] 2.19 [1.54-3.10]) in model 1 and (2.26 [1.56
      3.28]) model 2. CONCLUSIONS: Low serum 1,5-AG levels could be a possible marker
      for AIS/TIA risk in patients with well-controlled DM.

PMID- 29073615
TI  - Mir-144-3p Promotes Cell Proliferation, Metastasis, Sunitinib Resistance in Clear
      Cell Renal Cell Carcinoma by Downregulating ARID1A.
AB  - BACKGROUND/AIMS: We previously performed microRNA (miRNA) microarray to identify
      effective indicators of clear cell renal cell carcinoma (ccRCC) tissue samples
      and preoperative/postoperative plasma in which we identified miR-144-3p as an
      oncomiRNA. However, the molecular mechanism of miR-144-3p remains unclear. This
      study aims to explore the roles of miR-144-3p in the invasion, migration and
      Sunitinib-resistance in ccRCC and to elucidate the underlying mechanisms.
      METHODS: Gain and loss of function approaches were used to investigate the cell
      proliferation, cycle distribution, clonogenicity, migration, invasion,
      chemosensitivity of miR-144-3p in vitro. The xenograft model was used to assess
      the effects of miR-144-3p overexpression on tumorigenesis. Bioinformatics
      analysis and dual-luciferase reporter assay were used to indentify AT-rich
      interactive domain 1A (ARID1A) as a direct target gene of miR-144-3p.
      Quantitative RT-PCR, Western blotting, and immunohistochemical (IHC) staining
      were used to explore ARID1A expression level of the mRNA and protein. RESULTS: We
      found that miR-144-3p overexpression enhanced cell proliferation, clonogenicity,
      migration, invasion, and chemoresistance in ccRCC cells. Notably, the oncotumor
      activities of miR-144-3p were mediated by repressing the expression of ARID1A.
      The downregulation of ARIDIA could promote the function of miR-144-3p in cell
      proliferation, metastasis and chemoresistance. Consistently, ARID1A mRNA and
      protein levels were decreased in ccRCC and in nude mice, and they negatively
      correlated with miR-144-3p. CONCLUSION: Higher miR-144-3p may enhance malignancy
      and resistance to Sunitinib in ccRCC by targeting ARID1A, the observations may
      uncover novel strategies of ccRCC treatment.

PMID- 29073617
TI  - Preimplantation Factor (PIF) Promotes HLA-G, -E, -F, -C Expression in JEG-3
      Choriocarcinoma Cells and Endogenous Progesterone Activity.
AB  - BACKGROUND/AIMS: Pregnancy success requires mandatory maternal tolerance of the
      semi/ allogeneic embryo involving embryo-derived signals. Expression levels of
      PreImplantation Factor (PIF), a novel peptide secreted by viable embryos,
      correlate with embryo development, and its early detection in circulation
      correlates with a favourable pregnancy outcome. PIF enhances endometrial
      receptivity to promote embryo implantation. Via the p53 pathway, it increases
      trophoblast invasion, improving cell survival / immune privilege. PIF also
      reduces spontaneous and LPS-induced foetal death in immune naive murine model. We
      examined PIF effect on gene expression of human leukocyte antigen (HLA-G, -E -F
      and -C) and the influence of PIF on local progesterone activity in JEG-3
      choriocarcinoma cells. METHODS: PIF and progesterone (P4) effects on JEG-3 cells
      surface and intracellular HLA molecules was tested using monoclonal antibodies,
      flow cytometry, and Western blotting. PIF and IL17 effects on P4 and cytokines
      secretion was determined by ELISA. PIF and P4 effects on JEG-3 cells proteome was
      examined using 2D gel staining followed by spot analysis, mass spectrometry and
      bioinformatic analysis. RESULTS: In cytotrophoblastic JEG-3 cells PIF increased
      intracellular expression of HLA-G, HLA-F, HLA-E and HLA-C and surface expression
      of HLA-G, HLA-E and HLA-C in dose and time dependent manner. In case of HLA-E, -F
      results were confirmed also by Western blot. Proteome analysis confirmed an
      increase in HLA-G, pro-tolerance FOXP3+ regulatory T cells (Tregs), coagulation
      factors and complement regulator. In contrast, PIF reduced PRDX2 and HSP70s to
      negate oxidative stress and protein misfolding. PIF enhanced local progesterone
      activity, increasing steroid secretion and the receptor protein. It also promoted
      the secretion of the Th1/Th2 cytokines (IL-10, IL-1beta, IL-8, GM-CSF and TGF
      beta1), resulting in improved maternal signalling. CONCLUSION: PIF can generate a
      pro-tolerance milieu by enhancing the expression of HLA molecules and by
      amplifying endogenous progesterone activity. A Fast-Track clinical trial for
      autoimmune disease has been satisfactorily completed. The acquired data warrants
      PIF use for the treatment of early pregnancy disorders.

PMID- 29073618
TI  - Acoustic Realization and Inventory Size: Kannada and Malayalam Alveolar/Retroflex
      Laterals and /r/.
AB  - This study examines formant and spectral moment data for the apical and retroflex
      lateral sounds /l l/ of the Dravidian languages Kannada and Malayalam, together
      with the rhotic /r/ of Malayalam. Data are presented for 10 male speakers of each
      language. We find that the first spectral moment is lower for retroflex laterals
      than for alveolar laterals, and lower for the rhotic /r/ of Malayalam than for
      the retroflex lateral in the same language. Differences emerge when the retroflex
      lateral of Kannada is compared with the same sound in Malayalam. For both
      languages, F1 is higher and F3 and F4 are lower for the retroflex /l/ than for
      the alveolar /l/. However, F2 is higher for the retroflex than for the alveolar
      sound in Kannada, but lower in Malayalam. This difference is also reflected in
      differences in the second spectral moment between the languages. It is suggested
      that since proximity of F2 and F3 is known to be a defining feature of the rhotic
      /r/ in Malayalam, principles of phonetic dispersion apply to keep F2 from
      becoming too close to F3 for the retroflex lateral /l/ of Malayalam, but not for
      the same sound in Kannada.

PMID- 29073619
TI  - Sodium Chloride Supplementation Is Not Routinely Performed in the Majority of
      German and Austrian Infants with Classic Salt-Wasting Congenital Adrenal
      Hyperplasia and Has No Effect on Linear Growth and Hydrocortisone or
      Fludrocortisone Dose.
AB  - INTRODUCTION: Sodium chloride supplementation in salt-wasting congenital adrenal
      hyperplasia (CAH) is generally recommended in infants, but its implementation in
      routine care is very heterogeneous. OBJECTIVE: To evaluate oral sodium chloride
      supplementation, growth, and hydrocortisone and fludrocortisone dose in infants
      with salt-wasting CAH due to 21-hydroxylase in 311 infants from the AQUAPE CAH
      database. RESULTS: Of 358 patients with classic CAH born between 1999 and 2015,
      311 patients had salt-wasting CAH (133 females, 178 males). Of these, 86 patients
      (27.7%) received oral sodium chloride supplementation in a mean dose of 0.9 +/-
      1.4 mmol/kg/day (excluding nutritional sodium content) during the first year of
      life. 225 patients (72.3%) were not treated with sodium chloride. The percentage
      of sodium chloride-supplemented patients rose from 15.2% in children born 1999
      2004 to 37.5% in children born 2011-2015. Sodium chloride-supplemented and 
      unsupplemented infants did not significantly differ in hydrocortisone and
      fludrocortisone dose, target height-corrected height-SDS, and BMI-SDS during the
      first 2 years of life. CONCLUSION: In the AQUAPE CAH database, approximately one
      third of infants with salt-wasting CAH receive sodium chloride supplementation.
      Sodium chloride supplementation is performed more frequently in recent years.
      However, salt supplementation had no influence on growth, daily fludrocortisone
      and hydrocortisone dose, and frequency of adrenal crisis.

PMID- 29073620
TI  - Activation of ERK and Mutual Regulation of Stat3 and SP1 Contribute to Inhibition
      of PDK1 Expression by Atractylenolide-1 in Human Lung Cancer Cells.
AB  - BACKGROUND/AIMS: Atractylodes macrocephula Koidz is an important ingredient in
      traditional Chinese herbs. One major bioactive compound, atractylenolide-1 (ATL
      1), was reported to have anti-inflammatory and anti-tumor activities. However,
      the underlying molecular mechanism associated to this has not been well
      elucidated. METHODS: Cell viability and cell cycle distribution were measured
      using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and
      flow cytometry assays, respectively. Western blot analysis was performed to
      examine the phosphorylation and protein expression of extracellular signaling
      regulated kinase 1/2 (ERK1/2), signal transducer and activator of transcription 3
      (Stat3), 3-phosphoinositide dependent protein kinase-1 (PDK1) and transcription
      factor SP1. QRT-PCR was used to examine the mRNA levels of PDK1 gene. Exogenously
      expressions of Stat3, PDK1 and SP1 were carried out by transient transfection
      assays. PDK1 promoter activity was measured by Secrete-Pair Dual Luminescence
      Assay Kit. A nude mice xenograft model was used to confirm the findings in vitro.
      RESULTS: We showed that ATL-1 inhibited human lung cancer cell growth and induced
      cell cycle arrest. Furthermore, we found that ATL-1 stimulated phosphorylation of
      ERK1/2, inhibited phosphorylation and protein expressions of Stat3 and SP1; the
      latter were abrogated in the presence of MEK/ERK inhibitor PD98059. Moreover, ATL
      1 reduced the protein, mRNA expression and promoter activity of PDK1.
      Intriguingly, exogenously expressed Stat3 and SP1 overcame ATL-1-inhibited SP1
      and Stat3, and PDK1 protein expressions, respectively. Moreover, overexpression
      of PDK1 resisted the ATL-1-inhibited lung cancer cell growth. In consistent with
      the results in vitro, ATL-1 inhibited tumor growth, protein expressions of Stat3,
      SP1 and PDK1, and induced phosphorylation of ERK1/2 in vivo. CONCLUSION: In
      summary, our results show that ATL-1 inhibits lung cancer cell growth through
      activation of ERK1/2, followed by suppressing SP1 protein expression. ATL-1 also
      reduces phosphorylation and protein levels of Stat3. These are mutual regulation
      between Stat3 and SP1 proteins affected by ATL-1. This ultimately suppresses PDK1
      gene expression. This study reveals a novel mechanism by which ATL-1 inhibits
      growth of lung cancer cells. Thus, targeting PDK1 pinpoints a potential in the
      lung cancer treatment.

PMID- 29073622
TI  - A Callosal Lesion.

PMID- 29073621
TI  - Sexually Dimorphic Epigenetic Regulation of Brain-Derived Neurotrophic Factor in
      Fetal Brain in the Valproic Acid Model of Autism Spectrum Disorder.
AB  - Prenatal exposure to the antiepileptic, mood-stabilizing drug, valproic acid
      (VPA), increases the incidence of autism spectrum disorders (ASDs); in utero
      administration of VPA to pregnant rodents induces ASD-like behaviors such as
      repetitive, stereotyped activity, and decreased socialization. In both cases,
      males are more affected than females. We previously reported that VPA,
      administered to pregnant mice at gestational day 12.5, rapidly induces a
      transient, 6-fold increase in BDNF (brain-derived neurotrophic factor) protein
      and mRNA in the fetal brain. Here, we investigate sex differences in the
      induction of Bdnf expression by VPA as well as the underlying epigenetic
      mechanisms. We found no sex differences in the VPA stimulation of total brain
      Bdnf mRNA as indicated by probing for the BDNF protein coding sequence (exon 9);
      however, stimulation of individual transcripts containing two of the nine 5'
      untranslated exons (5'UTEs) in Bdnf (exons 1 and 4) by VPA was greater in female
      fetal brains. These Bdnf transcripts have been associated with different cell
      types or subcellular compartments within neurons. Since VPA is a histone
      deacetylase inhibitor, covalent histone modifications at Bdnf 5'UTEs in the fetal
      brain were analyzed by chromatin immunoprecipitation. VPA increased the
      acetylation of multiple H3 and H4 lysine residues in the vicinity of exons 1, 2,
      4, and 6; minimal differences between the sexes were observed. H3 lysine 4
      trimethylation (H3K4me3) at those exons was also stimulated by VPA. Moreover, the
      VPA-induced increase in H3K4me3 at exons 1, 4, and 6 was significantly greater in
      females than in males, i.e., sexually dimorphic stimulation of H3K4me3 by VPA
      correlated with Bdnf transcripts containing exons 1 and 4, but not 6. Neither
      H3K27me3 nor cytosine methylation at any of the 117 CpGs in the vicinity of the
      transcription start sites of exons 1, 4, and 6 was affected by VPA. Thus, of the
      6 epigenetic marks analyzed, only H3K4me3 can account for the sexually dimorphic
      expression of Bdnf transcripts induced by VPA in the fetal brain. Preferential
      expression of exon 1- and exon 4-Bdnf transcripts in females may contribute to
      sex differences in ASDs by protecting females from the adverse effects of genetic
      variants or environmental factors such as VPA on the developing brain.

PMID- 29073624
TI  - Racial and Ethnic Disparities in Preterm Infant Mortality and Severe Morbidity: A
      Population-Based Study.
AB  - BACKGROUND: Disparities exist in the rates of preterm birth and infant mortality
      across different racial/ethnic groups. However, only a few studies have examined
      the impact of race/ethnicity on the outcomes of premature infants. OBJECTIVE: To
      report the rates of mortality and severe neonatal morbidity among multiple
      gestational age (GA) groups stratified by race/ethnicity. METHODS: A
      retrospective cohort study utilizing linked birth certificate, hospital
      discharge, readmission, and death records up to 1 year of life. Live-born infants
      <=36 weeks born in the period 2007-2012 were included. Maternal self-identified
      race/ethnicity, as recorded on the birth certificate, was used. ICD-9 diagnostic
      and procedure codes captured neonatal morbidities (intraventricular hemorrhage,
      retinopathy of prematurity, periventricular leukomalacia, bronchopulmonary
      dysplasia, and necrotizing enterocolitis). Multiple logistic regression was
      performed to evaluate the impact of race/ethnicity on mortality and morbidity,
      adjusting for GA, birth weight, sex, and multiple gestation. RESULTS: Our cohort
      totaled 245,242 preterm infants; 26% were white, 46% Hispanic, 8% black, and 12%
      Asian. At 22-25 weeks, black infants were less likely to die than white infants
      (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.62-0.94). However, black
      infants born at 32-34 weeks (OR 1.64; 95% CI 1.15-2.32) or 35-36 weeks (OR 1.57;
      95% CI 1.00-2.24) were more likely to die. Hispanic infants born at 35-36 weeks
      were less likely to die than white infants (OR 0.66; 95% CI 0.50-0.87). Racial
      disparities at different GAs were also detected for severe morbidities.
      CONCLUSIONS: The impact of race/ethnicity on mortality and severe morbidity
      varied across GA categories in preterm infants. Disparities persisted even after
      adjusting for important potential confounders.

PMID- 29073623
TI  - Kaempferol Alleviates Angiotensin II-Induced Cardiac Dysfunction and Interstitial
      Fibrosis in Mice.
AB  - BACKGROUND/AIMS: Endothelial-to-mesenchymal transition (EndMT) is a mechanism
      that promotes cardiac fibrosis induced by Angiotensin II (AngII). Kaempferol
      (KAE) is a monomer component mainly derived from the rhizome of Kaempferia
      galanga L. It shows anti-inflammatory, anti-oxidative, anti-microbial and anti
      cancer properties, which can be used in the treatment of cancer, cardiovascular
      diseases, infection, etc. But, its effects on the development of cardiac
      remodelling remain completely unknown. The aim of the present study was to
      determine whether KAE attenuates cardiac hypertrophy induced by angiotensin II
      (Ang II) in cultured neonatal rat cardiac myocytes in vitro and cardiac
      hypertrophy induced by AngII infusion in mice in vivo. METHODS: Male wild-type
      mice aged 8-10 weeks with or without KAE were subjected to AngII or saline, to
      induce fibrosis or as a control, respectively. Morphological changes,
      echocardiographic parameters, histological analyses, and hypertrophic markers
      were also used to evaluate hypertrophy. RESULTS: KAE prevented and reversed
      cardiac remodelling induced by AngII. The KAE in this model exerted no basal
      effects but attenuated cardiac fibrosis, hypertrophy and dysfunction induced by
      AngII. Both in vivo and in vitro experiments demonstrated that Ang II infusion or
      TGF-beta induced EndMT can be reduced by KAE and the proliferation and activation
      of cardiac fibroblasts (CFs) can be inhibited by KAE. CONCLUSIONS: The results
      suggest that KAE prevents and reverses ventricular fibrosis and cardiac
      dysfunction, providing an experimental basis for clinical treatment on
      ventricular fibrosis.

PMID- 29073625
TI  - IL-17 Activates the IL-6/STAT3 Signal Pathway in the Proliferation of Hepatitis B
      Virus-Related Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: We performed this study to determine the role of IL-17 in the
      immune microenvironment of hepatitis B virus- (HBV-) related hepatocellular
      carcinoma (HCC). METHODS: HepG2 cells were treated with IL-17, STAT3 inhibitor
      S31-201 or IL-6 neutralizing monoclonal antibody (IL-6 mAb). Cell proliferation
      and migration were compared using the Cell Counting kit-8 (CCK-8) and Transwell
      assays, respectively. Real-time quantitative PCR (RT-qPCR), Western Blot, ELISA,
      immunofluorescence and histological staining were used for determining the
      expression levels of IL-17, IL-6, MCP-1, CCL5, VEGF, STAT3 and p-STAT3. HCC
      xenograft models were constructed in wild type and IL-17 knockout mice to clarify
      the effects of IL-17 on HCC in vivo. RESULTS: Exogenous IL-17 enhanced the
      proliferation and migration of HepG2 cells, and it activated the phosphorylation
      of STAT3. RT-qPCR and ELISA showed that IL-17 promoted the expression of IL-6.
      The CCK-8 and Transwell assays showed that S31-201 or IL-6 mAb remarkably
      reversed the promotion effects of proliferation and migration by exogenous IL-17
      in HepG2 cells. Additionally, IL-6 could promote the phosphorylation of STAT3,
      while IL-6 mAb acted as an inhibitor, and exogenous IL-17 could neutralize the
      inhibitory effects of IL-6 mAb. In vivo, compared to the wild type mice, the
      tumor volume, weight, density and size were decreased in IL-17 knockout mice.
      Additionally, the expression levels of p-STAT3, IL-6, MCP-1, CCL5 and VEGF
      decreased in IL-17 knockout mice. CONCLUSIONS: IL-17 can enhance the
      proliferation of HepG2 cells in vitro and in vivo via activating the IL-6/STAT3
      pathway. Therefore, the IL-17/IL-6/STAT3 signaling pathway is a potential
      therapeutic target for HBV-related HCC.

PMID- 29073626
TI  - Diosgenin, an Activator of 1,25D3-MARRS Receptor/ERp57, Attenuates the Effects of
      TNF-alpha by Causing ADAM10-Dependent Ectodomain Shedding of TNF Receptor 1.
AB  - BACKGROUND/AIMS: We investigated how diosgenin, a steroidal sapogenin, has anti
      tumor necrosis factor-alpha (TNF-alpha) effects in human aortic endothelial cells
      (HAECs). METHODS: Tumor necrosis factor receptor 1 (TNFR1) was assessed by
      Western blot analysis. Intracellular Ca2+ was measured using Fluo-4 AM.
      Immunofluorescence staining was performed for a disintegrin and metalloprotease
      10 (ADAM10). RESULTS: Diosgenin (1 ~ 100 nM) induced ectodomain shedding of TNFR1
      within 30 min and attenuated TNF-alpha-induced intercellular adhesion molecule-1
      (ICAM-1) expression. Upon treatment with diosgenin, extracellular Ca2+ entered
      into the cells via L-type calcium channels, whereas diosgenin-induced ectodomain
      shedding of TNFR1 was almost completely inhibited by BAPTA-AM (intracellular Ca2+
      chelator), verapamil (L-type calcium channel antagonist) and the absence of
      extracellular Ca2+. Diosgenin caused translocation of ADAM10 to the cell surface,
      which was mediated by extracellular Ca2+ influx. Depletion of ADAM10 prevented
      diosgenin-induced ectodomain shedding of TNFR1 and abolished the inhibitory
      effect of diosgenin on TNF-alpha-induced ICAM-1 expression. Diosgenin did not
      induce extracellular Ca2+ influx and ectodomain shedding of TNFR1 in cells
      depleted of 1,25D3-membrane associated rapid response steroid-binding receptor
      (1,25D3-MARRS receptor/ERp57). CONCLUSION: Diosgenin elicits L-type calcium
      channel-mediated extracellular Ca2+ influx, and thereby induces ADAM10-mediated
      ectodomain shedding of TNFR1. This effect of diosgenin was exerted through 1,25D3
      MARRS receptor/ERp57.

PMID- 29073627
TI  - Gene Expression and Apoptosis Levels in Cumulus Cells of Patients with
      Polymorphisms of FSHR and LHB Undergoing in Vitro Fertilization Program.
AB  - BACKGROUND/AIMS: FSH receptor (FSHR) Ala307Thr and Asn680Ser and LHbeta chain
      (LHB) Trp28Arg and Ile35Thr polymorphisms affect the response to pharmacological
      ovarian stimulation with r-FSH in women undergoing assisted reproductive
      treatment (ART). Here, we evaluated the expression level of selected genes
      involved in follicle maturation and the possible onset of apoptosis in cumulus
      cells of patients with single and double FSHR and LHB polymorphisms, as potential
      markers of oocyte competence. METHODS: Cumulus cells from 36 stimulated patients
      were collected and SNP genotyping performed by PCR. Gene expression was evaluated
      through real-time PCR, and apoptosis estimated via TUNEL assay, and cleaved
      caspase-3 and pAKT immunostaining. RESULTS: The cumulative data show significant
      correlations indicating that the genetic alteration of FSHR and/or LHB genes may
      lead to perturbations of the signaling network programmed to granulosa cell
      survival and follicle development. Notably, when double heterozygotes were
      compared to the rest of the patients, a higher level of apoptosis in terms of
      both DNA fragmentation index and amount of active caspase-3 was observed in
      cumulus cells. CONCLUSIONS: These results may help to define personalized
      stimulation protocols in ART programs, to increase the success rate of ICSI
      procedures in accordance with the polymorphic condition of the individual
      patient.

PMID- 29073628
TI  - Transient Congenital Hypothyroidism Alters Gene Expression of Glucose
      Transporters and Impairs Glucose Sensing Apparatus in Young and Aged Offspring
      Rats.
AB  - BACKGROUND/AIMS: Transient congenital hypothyroidism (TCH) could disturb
      carbohydrate metabolism in adulthood. Aging is associated with increased risk of
      type 2 diabetes. This study aims to address effects of TCH on mRNA expressions of
      glucose transporters (GLUTs) and glucokinase (GcK) in islets and insulin target
      tissues of aged offspring rats. METHODS: The TCH group received water containing
      0.025% 6-propyl-2-thiouracil during gestation. Offspring from control and TCH
      groups (n=6 in each group) were followed until month 19. Gene expressions of
      GLUTs and GcK were measured at months 3 and 19. RESULTS: Compared to controls,
      aged TCH rats had higher GLUT4 expression in heart (4.88 fold) and soleus (6.91
      fold), while expression was lower in epididymal fat (12%). In TCH rats, GLUT2 and
      GcK expressions in islets were lower in young (12% and 10%, respectively) and
      higher in aged (10.85 and 8.42 fold, respectively) rats. In addition, liver GLUT2
      and GcK expressions were higher in young (13.11 and 21.15 fold, respectively) and
      lower in aged rats (44% and 5%, respectively). CONCLUSION: Thyroid hormone
      deficiency during fetal period impaired glucose sensing apparatus and changed
      glucose transporter expression in insulin-sensitive tissues of aged offspring
      rats. These changes may contribute to impaired carbohydrate metabolism.

PMID- 29073629
TI  - Early Cognitive Impairment after Intracerebral Hemorrhage in the INTERACT1 Study.
AB  - BACKGROUND: Data on cognitive impairment after acute intracerebral hemorrhage
      (ICH) are limited. This study is aimed at determining the frequency and
      predictors of cognitive impairment among participants of the pilot phase,
      Intensive Blood Pressure (BP) Reduction in Acute Cerebral Hemorrhage Trial
      (INTERACT1). METHODS: INTERACT1 was an open randomized trial of early intensive
      (target systolic BP <140 mm Hg) compared with contemporaneous guideline
      recommended BP lowering in 404 patients with elevated systolic BP (150-220 mm Hg)
      within 6 h of ICH onset. Cognitive impairment was defined by scores <=24 on the
      Mini-Mental State Examination (MMSE) assessed by interview on follow-up at 90
      days. RESULTS: A total of 231 (64.5%) of 358 90-day survivors had MMSE scores for
      analyses, and 75 (32.5%) had cognitive impairment. In multivariable analysis,
      older age (OR 2.48, 95% CI 1.73-3.56 per 10-year increase; p < 0.001), female sex
      (OR 2.06, 95% CI 1.00-4.23; p = 0.049), prior ICH (OR 2.87, 95% CI 1.08-7.65; p =
      0.035), high baseline National Institute of Health Stroke Scale score (OR 1.06,
      95% CI 1.00-1.13; p = 0.044), and high mean systolic BP over the first 24 h post
      randomization (OR 1.34, 95% CI 1.07-1.68/10 mm Hg increase; p = 0.011) were
      independently associated with cognitive impairment. CONCLUSIONS: One third of
      patients have significant cognitive impairment early after ICH, which is more
      frequent in the elderly, females, those with prior ICH, and more severe initial
      neurological deficit and with persistently high early systolic BP.

PMID- 29073631
TI  - Isolated Cleft Lip and Palate: Maxillary Gap Sign and Palatino-Maxillary Diameter
      at 11-13 Weeks.
AB  - OBJECTIVE: To evaluate the maxillary gap sign and describe markers for the first
      trimester diagnosis of isolated cleft lip and palate (CLP) at 11-13 weeks.
      METHODS: Firstly, this was a prospective assessment of 1,087 fetuses including 5
      cases of isolated CLP in 2 centers which were referred for the 11-13 weeks scan.
      Secondly, intra- and interobserver variability of the maxillary gap sign was
      evaluated for observers R.L. and A.B. in 2 sessions (affected cases vs. 50 normal
      fetuses in each session) to reduce the bias of different ultrasound manufacturer
      visualizations (Philips, GE). Thirdly, the palatino-maxillary diameter (PMD) was
      examined in stored images, DICOM loops and volumes of the midsagittal and
      parasagittal view of the fetal head and brain at 11+0-13+6 weeks of gestation
      from 5 fetuses with isolated CLP and 302 consecutively assessed normal controls.
      The PMD values in fetuses with isolated CLP and normal controls were compared.
      RESULTS: Firstly, 5 out of 6 referred pregnancies with isolated CLP were detected
      prospectively using the midsagittal view for measurement of nuchal translucency
      due to an abnormal appearance. One out of 6 patients with isolated CLP declined
      the 11-13 weeks scan. Secondly, intra- and interobserver variability showed no
      false positive cases; all cases with isolated CLP were identified by both
      sonographers; however, in 2 cases the maxillary gap sign was doubtful. Therefore,
      thirdly, we developed the PMD measurement which increased significantly with
      crown-rump length (CRL) from respective mean values at CRL of 45 mm to 4.66 mm
      and to 8.95 mm at CRL of 84 mm. In the CLP group, the PMD was below the 5th
      percentile of the control group in 4 out of 5 (80%) cases. CONCLUSIONS: The
      midsagittal view for measurement of nuchal translucency shows a high
      reproducibility regarding abnormal views for maxillary gap sign. In the
      midsagittal view of the fetal head, face, and brain at 11-13 weeks, the majority
      of fetuses with isolated CLP have a measurable abnormality in addition, the PMD.

PMID- 29073630
TI  - MicroRNA-30a-5p Inhibits the Growth of Renal Cell Carcinoma by Modulating GRP78
      Expression.
AB  - BACKGROUND/AIMS: MiR-30a-5p, a member of the microRNA-30 family (miR-30), is
      known to function as a tumor suppressor in several different cancers. However,
      the expression levels, biological function, and underlying mechanisms of miR-30a
      5p in renal cell carcinoma (RCC) remain unclear. Glucose-regulated protein78
      (GRP78) is a common cancer biomarker and promotes the growth and survival of
      cancer cells. The expression of GRP78 has been reported to be modulated by miR
      30a in neurons. In this study, the expression profile of miR-30a-5p in clear cell
      renal cell carcinoma (ccRCC) and its effect on ccRCC through regulating GRP78
      expression was investigated. METHODS: MiR-30a-5p expression was analyzed using
      bioinformatic software on open microarray datasets from the Cancer Genome Atlas
      (TCGA) and Gene Expression Omnibus (GEO), and confirmed by quantitative RT-PCR
      (qRT-PCR) in ccRCC cell lines. Cell proliferation was investigated using CCK-8
      and cell count assays. Western blotting, immunohistochemistry, luciferase
      reporter assays, and flow cytometry were employed to investigate the mechanisms
      of the effect of miR-30a-5p on ccRCC Results: MiR-30a-5p was down-regulated in
      ccRCC and related to the clinicopathological factors and prognosis of ccRCC. MiR
      30a-5p was found to both suppress the growth of ccRCC cells and promote apoptosis
      of ccRCC cells in vitro. GRP78 was the direct target gene of miR-30a-5p, and the
      GRP78 expression was inversely correlated with the expression of miR-30a-5p in
      vivo and in vitro. The functional studies of GRP78 overexpression or knockdown
      demonstrated that GRP78 promoted proliferation and anti-apoptosis of ccRCC cells,
      and the oncogenic activity of GRP78 resulting in by miR-30a-5p overexpression.
      CONCLUSION: MiR-30a-5p is a bona fide negative regulator of GRP78 expression, and
      the anti-tumor activity of miR-30a-5p in ccRCC is due at least in part to down
      regulating GRP78 expression and modulating the unfolded protein response (UPR)
      pathway. Thus, miR-30-GRP78 interaction provides a novel therapeutic candidate
      target in ccRCC treatment.

PMID- 29073632
TI  - Jean-Martin Charcot (1825-1893): A Treatment Approach Gone Astray?
AB  - Jean-Martin Charcot's reputation remains that of a physician who took little
      interest in treatments for the neurological diseases he did much to identify.
      After reviewing the limited number of medicinal remedies of slight effectiveness
      at Charcot's disposal, we analyze in this review the numerous therapeutic tests
      that he conducted: vibratory medicine for Parkinson's disease, treatment of tabes
      by suspension technique, metallotherapy and moral -treatment for hysteria.
      Understanding that he fully and completely adhered to the far-reaching heredity
      based theories of his day makes it possible to perceive his natural and
      fundamental pessimism. By drawing on both -ancestral traditions and innovative
      approaches, Charcot "combined genius with charlatanism" in a surprising way: he
      demonstrated genius in the area of nosology, and a sort of charlatanism in the
      area of treatments.

PMID- 29073634
TI  - Demographic, Clinical and Polysomnographic Characteristics of Childhood- and
      Adult-Onset Sleepwalking in Adults.
AB  - BACKGROUND: Sleepwalking (SW) is found to affect children predominantly, but it
      can persist or appear de novo even among adults. In this study, we assessed the
      demographic, clinical and polysomnographic profile, trigger factors and
      associated comorbidities of adult-onset (AO-SW) and childhood-onset (CO-SW) adult
      sleepwalkers. METHODS: In adult sleepwalkers, a structured clinical interview, a
      battery of questionnaires, video-polysomnography (v-PSG) and standard
      electroencephalography (EEG) were performed. RESULTS: Among 63 sleepwalkers, 45%
      had >=1 episodes/month, 54% had partial recall of the episodes and 36% reported
      trigger factors for SW. Almost all subjects reported co-occurring parasomnias. In
      v-PSG, 4% exhibited episodes of SW, 17% confusional arousals, 21% had an
      increased apnea-hypopnea-index and 6% exhibited features of an overlap parasomnia
      disorder. In our cohort, 73% reported CO-SW and 27% AO-SW. In subjects with AO
      SW, positive family history for parasomnias was found in 33% (vs. 49% in CO-SW),
      neurological comorbidities in 44% (vs. 14%), psychiatric comorbidities in 25%
      (vs. 33%), EEG abnormalities in 50% (vs. 29%). Violence during SW episodes was
      more frequent in males and in subjects with CO-SW (45% for self-injury and 44%
      for violent behaviour vs. 33 and 29% respectively in the AO-SW group).
      CONCLUSIONS: Adult SW represents a complex and potentially dangerous condition.
      The characteristics of AO-SW often differ from those of CO-SW.

PMID- 29073635
TI  - Huntington's Disease: Premotor Phase.
AB  - Huntington's disease (HD) is an incurable, neurodegenerative disease, which
      manifests via a triad of progressive symptoms: motor impairment, psychiatric
      disorders, and cognitive decline. Conventionally, the HD diagnosis is based on
      the presence of involuntary choreiform movements and a positive genetic test for
      the CAG-expanded allele gene. Although the diagnosis focuses on the motor part of
      the triad, there is increasing evidence that both cognitive and neuropsychiatric
      symptoms can, and often do, present decades before the onset of motor symptoms.
      In this paper, we review the evidence regarding the symptoms in the HD premotor
      phase and summarize the most relevant and robust studies in the last few years.
      Regarding neuropsychiatric symptoms, higher levels of depression, anxiety,
      apathy, irritability, psychosis, disinhibition, hostility, and sleeping problems
      were found. In terms of cognition, there was impairment in attention, working
      memory, episodic memory, language, recognition of facial emotions, empathy, and
      theory of mind. These early symptoms of HD can be very debilitating and are often
      disregarded by doctors. It is necessary to acknowledge them so that they can be
      treated or alleviated. Moreover, an earlier diagnosis can lead to the
      implementation of neurodegenerative prevention therapies, which may slow the
      progression of the disease and prolong overall functioning. This will improve the
      patient's independence and their quality of life.

PMID- 29073637
TI  - Tetracycline use and risk of incident skin cancer: a prospective study.
AB  - BACKGROUND: Tetracycline is a photosensitising medication that increases skin
      vulnerability to UV-related damage. METHODS: We prospectively examined
      tetracycline use and risk of incident melanoma, squamous cell carcinoma (SCC),
      and basal cell carcinoma (BCC) based on 213 536 participants from the Nurses'
      Health Study (NHS), NHS2, and Health Professionals Follow-up Study. Information
      on ever use of tetracycline was asked via questionnaire. Diagnoses of melanoma
      and SCC were pathologically confirmed. RESULTS: Tetracycline use was associated
      with a modestly increased risk of BCC (ncase=36 377), with a pooled hazard ratio
      (HR) of 1.11 (95% confidence interval (CI)=1.02-1.21, P-trend=0.05 by duration of
      use). Tetracycline use was not significantly associated with melanoma
      (ncase=1831, HR=1.09, 95% CI=0.94-1.27) or SCC (ncase=3332, HR=1.04, 95% CI=0.91
      1.18) risk overall. However, we observed positive interactions between
      tetracycline use and adulthood UV exposure on SCC risk (P-interaction=0.05).
      CONCLUSION: Tetracycline use was associated with a modestly increased risk of
      BCC, but was not associated with melanoma or SCC.

PMID- 29073636
TI  - Global metabolomic profiling of uterine leiomyomas.
AB  - BACKGROUND: Uterine leiomyomas can be classified into molecularly distinct
      subtypes according to their genetic triggers: MED12 mutations, HMGA2
      upregulation, or inactivation of FH. The aim of this study was to identify
      metabolites and metabolic pathways that are dysregulated in different subtypes of
      leiomyomas. METHODS: We performed global metabolomic profiling of 25 uterine
      leiomyomas and 17 corresponding myometrium specimens using liquid chromatography
      tandem mass spectroscopy. RESULTS: A total of 641 metabolites were detected. All
      leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We
      identified a clearly distinct metabolomic profile for leiomyomas of the FH
      subtype, characterised by metabolic alterations in the tricarboxylic acid cycle
      and pentose phosphate pathways, and increased levels of multiple lipids and amino
      acids. Several metabolites were uniquely elevated in leiomyomas of the FH
      subtype, including N6-succinyladenosine and argininosuccinate, serving as
      potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12
      subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino
      acids, and dysregulation of vitamin C metabolism, a finding which was also
      compatible with gene expression data. CONCLUSIONS: The study reveals the
      metabolomic heterogeneity of leiomyomas and provides the requisite framework for
      strategies designed to target metabolic alterations promoting the growth of these
      prevalent tumours.

PMID- 29073640
TI  - Focus on spatial cognition.

PMID- 29073638
TI  - Intratumoural PD-L1 expression is associated with worse survival of patients with
      Epstein-Barr virus-associated gastric cancer.
AB  - BACKGROUND: This study investigated the clinical relevance and prognostic impact
      of the overall expression of programmed cell death protein ligand-1 (PD-L1) and
      programmed cell death protein ligand-2 (PD-L2), in patients with Epstein-Barr
      virus-associated gastric cancer (EBVaGC). METHODS: After reviewing 1318
      consecutive cases of surgically resected or endoscopic submucosal dissected
      gastric cancers, the expression status of PD-L1 and PD-L2 in 120 patients with
      EBVaGC identified by EBV-encoded RNA in situ hybridisation was retrospectively
      analysed using immunohistochemistry (IHC). For each IHC marker, positivity was
      separately in intraepithelial tumour cells (iTu-) and immune cells in the tumour
      stroma area (str-). RESULTS: Among 116 eligible patients, 57 (49.1%) and 66
      patients (56.9%) were determined as iTu-PD-L1-positive and str-PD-L1-positive,
      respectively, whereas 23 (21.6%) and 45 patients (38.8%) were determined as iTu
      PD-L2 positive and str-PD-L2 positive, respectively. Intraepithelial tumour cell
      PD-L1 positivity was found to be significantly associated with lymph node (LN)
      metastasis (P=0.012) and a poor disease-free survival (DFS) (P=0.032), yet not
      overall survival (P=0.482). In a multivariate analysis, iTu-PD-L1 positivity was
      independently associated with a poor DFS (P=0.006, hazard ratio=12.085). In
      contrast, str-PD-L2-positivity was related to a lower T category (P=0.003),
      absence of LN metastasis (P=0.032) and perineural invasion (P=0.028).
      Intraepithelial tumour cell and str-PD-L2 positivity showed a trend towards an
      improved DFS, although not significant (P=0.060 and P=0.073, respectively).
      CONCLUSIONS: Intraepithelial tumour cells PD-L1 expression can be used to predict
      a poor outcome in patients with EBVaGC and can represent a rational approach for
      PD-1/PD-L pathway-targeted immunotherapy.

PMID- 29073639
TI  - Our sense of direction: progress, controversies and challenges.
AB  - In this Perspective, we evaluate current progress in understanding how the brain
      encodes our sense of direction, within the context of parallel work focused on
      how early vestibular pathways encode self-motion. In particular, we discuss how
      these systems work together and provide evidence that they involve common
      mechanisms. We first consider the classic view of the head direction cell and
      results of recent experiments in rodents and primates indicating that inputs to
      these neurons encode multimodal information during self-motion, such as
      proprioceptive and motor efference copy signals, including gaze-related
      information. We also consider the paradox that, while the head-direction network
      is generally assumed to generate a fixed representation of perceived directional
      heading, this computation would need to be dynamically updated when the
      relationship between voluntary motor command and its sensory consequences
      changes. Such situations include navigation in virtual reality and head
      restricted conditions, since the natural relationship between visual and
      extravisual cues is altered.

PMID- 29073642
TI  - Synuclein and dopamine: the Bonnie and Clyde of Parkinson's disease.

PMID- 29073643
TI  - Howard Eichenbaum 1947-2017.

PMID- 29073641
TI  - Viewpoints: how the hippocampus contributes to memory, navigation and cognition.

PMID- 29073646
TI  - Polymorphic computation in locus coeruleus networks.

PMID- 29073647
TI  - The cingulate cortex: divided in pain.

PMID- 29073645
TI  - Integration of objects and space in perception and memory.
AB  - Distinct processing of objects and space has been an organizing principle for
      studying higher-level vision and medial temporal lobe memory. Here, however, we
      discuss how object and spatial information are in fact closely integrated in
      vision and memory. The ventral, object-processing visual pathway carries precise
      spatial information, transformed from retinotopic coordinates into relative
      dimensions. At the final stages of the ventral pathway, including the dorsal
      anterior temporal lobe (TEd), object-sensitive neurons are intermixed with
      neurons that process large-scale environmental space. TEd projects primarily to
      perirhinal cortex (PRC), which in turn projects to lateral entorhinal cortex
      (LEC). PRC and LEC also combine object and spatial information. For example, PRC
      and LEC neurons exhibit place fields that are evoked by landmark objects or the
      remembered locations of objects. Thus, spatial information, on both local and
      global scales, is deeply integrated into the ventral (temporal) object-processing
      pathway in vision and memory.

PMID- 29073651
TI  - Time for healthy investment.

PMID- 29073648
TI  - Synaptic integrative mechanisms for spatial cognition.
AB  - Synaptic integrative mechanisms have profound effects on electrical signaling in
      the brain that, although largely hidden from recording methods that observe the
      spiking activity of neurons, may be critical for the encoding, storage and
      retrieval of information. Here we review roles for synaptic integrative
      mechanisms in the selection, generation and plasticity of place and grid fields,
      and in related temporal codes for the representation of space. We outline
      outstanding questions and challenges in the testing of hypothesized models for
      spatial computation and memory.

PMID- 29073644
TI  - Spatial representation in the hippocampal formation: a history.
AB  - Since the first place cell was recorded and the cognitive-map theory was
      subsequently formulated, investigation of spatial representation in the
      hippocampal formation has evolved in stages. Early studies sought to verify the
      spatial nature of place cell activity and determine its sensory origin. A new
      epoch started with the discovery of head direction cells and the realization of
      the importance of angular and linear movement-integration in generating spatial
      maps. A third epoch began when investigators turned their attention to the
      entorhinal cortex, which led to the discovery of grid cells and border cells.
      This review will show how ideas about integration of self-motion cues have shaped
      our understanding of spatial representation in hippocampal-entorhinal systems
      from the 1970s until today. It is now possible to investigate how specialized
      cell types of these systems work together, and spatial mapping may become one of
      the first cognitive functions to be understood in mechanistic detail.

PMID- 29073652
TI  - Rationing access to deceased donor kidney transplantation: New Zealand charts her
      own course.

PMID- 29073649
TI  - Cell types for our sense of location: where we are and where we are going.
AB  - Technological advances in profiling cells along genetic, anatomical and
      physiological axes have fomented interest in identifying all neuronal cell types.
      This goal nears completion in specialized circuits such as the retina, while
      remaining more elusive in higher order cortical regions. We propose that this
      differential success of cell type identification may not simply reflect
      technological gaps in co-registering genetic, anatomical and physiological
      features in the cortex. Rather, we hypothesize it reflects evolutionarily driven
      differences in the computational principles governing specialized circuits versus
      more general-purpose learning machines. In this framework, we consider the
      question of cell types in medial entorhinal cortex (MEC), a region likely to be
      involved in memory and navigation. While MEC contains subsets of identifiable
      functionally defined cell types, recent work employing unbiased statistical
      methods and more diverse tasks reveals unsuspected heterogeneity and adaptivity
      in MEC firing patterns. This suggests MEC may operate more as a generalist
      circuit, obeying computational design principles resembling those governing other
      higher cortical regions.

PMID- 29073653
TI  - The state of quality improvement and patient safety teaching in health
      professional education in New Zealand.
AB  - AIM: To investigate how quality and patient safety domains are being taught in
      the pre-registration curricula of health profession education programmes in New
      Zealand. METHODS: All tertiary institutions providing training for medicine,
      nursing, midwifery, dentistry, pharmacy, physiotherapy, dietetics and 11 other
      allied health professions in New Zealand were contacted and a person with
      relevant curriculum knowledge was invited to participate. Interviews were
      conducted using a semi-structured interview guide to explore nine quality and
      safety domains; improvement science, patient safety, quality and safety culture,
      evidence-based practice, patient-centred care, teamwork and communication,
      leadership for change, systems thinking and use of information technology (IT).
      Transcribed data were extracted and categorised by discipline and domain. Two
      researchers independently identified and categorised themes within each domain,
      using a general inductive approach. RESULTS: Forty-nine institutions were
      contacted and 43 (88%) people were interviewed. The inclusion and extent of
      quality and safety teaching was variable. Evidence-based practice, patient
      centred care and teamwork and communication were the strongest domains and well
      embedded in programmes, while leadership, systems thinking and the role of IT
      were less explicitly included. Except for two institutions, improvement science
      was absent from pre-registration curricula. Patient safety teaching was focused
      mainly around incident reporting, and to a lesser extent learning from adverse
      events. Although a 'no blame' culture was articulated as important, the theme of
      individual accountability was still apparent. While participants agreed that all
      domains were important, the main barriers to incorporating improvement science
      and patient safety concepts into existing programmes included an 'already
      stretched curriculum' and having faculty with limited expertise in these areas.
      CONCLUSIONS: Although the building blocks for improving the quality and safety of
      healthcare are present, this national study of multiple health professional pre
      registration education programmes has identified teaching gaps in patient safety
      and improvement science methods and tools. Failure to address these gaps will
      compromise the ability of new graduates to successfully implement and sustain
      improvements.

PMID- 29073654
TI  - The outcomes of patients returned to general practitioner after being declined
      hip and knee replacement.
AB  - AIM: To determine the outcome of patients waitlisted for hip and knee replacement
      surgery who were returned to GP due to resource constraints. METHODS:
      Prospectively gathered data of all patients returned to GP was analysed,
      including demographics, clinical prioritisation scores and patient-reported
      scores. Subsequent outcome was collected from departmental records and the
      National Joint Registry. RESULTS: Between November 2013 and December 2015, 374
      patients were returned to GP care. At minimum 12-month follow-up, 215 (57.5%) had
      undergone or had certainty for surgery, 36 patients (9.6%) had been re-referred
      and again declined surgery and 123 (32.9%) remained in GP care. The factors
      influencing the likelihood of a patient subsequently qualifying for surgery were
      need for hip rather than knee replacement, time from initial FSA and initial NZOA
      score. The mean waiting time for those patients who underwent publicly-funded
      surgery was 14.7 months. CONCLUSION: Returning patients to GP delays treatment
      rather than reducing the need for surgery. This delay results in waste, added
      costs to the patient, healthcare system and society, and may reduce the benefit
      of surgery. There needs to be a significant increase in capacity to meet this
      demand.

PMID- 29073650
TI  - The cognitive map in humans: spatial navigation and beyond.
AB  - The 'cognitive map' hypothesis proposes that brain builds a unified
      representation of the spatial environment to support memory and guide future
      action. Forty years of electrophysiological research in rodents suggest that
      cognitive maps are neurally instantiated by place, grid, border and head
      direction cells in the hippocampal formation and related structures. Here we
      review recent work that suggests a similar functional organization in the human
      brain and yields insights into how cognitive maps are used during spatial
      navigation. Specifically, these studies indicate that (i) the human hippocampus
      and entorhinal cortex support map-like spatial codes, (ii) posterior brain
      regions such as parahippocampal and retrosplenial cortices provide critical
      inputs that allow cognitive maps to be anchored to fixed environmental landmarks,
      and (iii) hippocampal and entorhinal spatial codes are used in conjunction with
      frontal lobe mechanisms to plan routes during navigation. We also discuss how
      these three basic elements of cognitive map based navigation-spatial coding,
      landmark anchoring and route planning-might be applied to nonspatial domains to
      provide the building blocks for many core elements of human thought.

PMID- 29073655
TI  - Deceased donor kidney transplantation in New Zealand: use and audit of a survival
      prediction tool.
AB  - AIMS: New Zealand follows the guideline that only patients with projected five
      year survival of 80% are listed for deceased donor kidney transplantation. An
      algorithm derived from US data estimates survival after transplantation, however,
      this may not be as applicable to the New Zealand population. We review use of the
      US derived algorithm in New Zealand. We assessed accuracy of scores calculated by
      referring units and audited whether the system is applied in New Zealand.
      METHODS: Data on 422 patients assessed for transplantation was entered into the
      algorithm to calculate a projected survival score. Scores were generated by an
      independent investigator and compared with those calculated by local units.
      Scores and demographics of listed and not-listed patients were also compared.
      RESULTS: Three hundred and twenty-five of 420 (77%) patients assessed were
      accepted onto the New Zealand transplant list. Mean estimated five-year survival
      in listed patients was 89.4% compared to 79.8% in those not accepted (p<0.0001).
      Listed patients were younger and less likely to have coronary artery disease
      (CAD). There was no significant difference in scores calculated by the
      independent assessor and referring centres (p=0.185). CONCLUSION: The algorithm
      is universally and accurately used. Future studies are required to determine the
      validity of the system in New Zealand patients.

PMID- 29073656
TI  - Gene expression profiling of breast tumours from New Zealand patients.
AB  - AIMS: New Zealand has one of the highest rates of breast cancer incidence in the
      world. We investigated the gene expression profiles of breast tumours from New
      Zealand patients, compared them to gene expression profiles of international
      breast cancer cohorts and identified any associations between altered gene
      expression and the clinicopathological features of the tumours. METHODS:
      Affymetrix microarrays were used to measure the gene expression profiles of 106
      breast tumours from New Zealand patients. Gene expression data from six
      international breast cancer cohorts were collated, and all the gene expression
      data were analysed using standard bioinformatic and statistical tools. RESULTS:
      Gene expression profiles associated with tumour ER and ERBB2 status, molecular
      subtype and selected gene expression signatures within the New Zealand cohort
      were consistent with those found in international cohorts. Significant
      differences in clinicopathological features such as tumour grade, tumour size and
      lymph node status were also observed between the New Zealand and international
      cohorts. CONCLUSIONS: Gene expression profiles, which are a sensitive indicator
      of tumour biology, showed no clear difference between breast tumours from New
      Zealand patients and those from non-New Zealand patients. This suggests that
      other factors may contribute to the high and increasing breast cancer incidence
      in New Zealand compared to international populations.

PMID- 29073657
TI  - Is cardiomegaly on chest radiograph representative of true cardiomegaly: a cross
      sectional observational study comparing cardiac size on chest radiograph to that
      on echocardiography.
AB  - AIMS: To determine whether or not cardiomegaly identified on chest radiograph
      (CXR) is indicative of true cardiomegaly as determined using echocardiography
      (echo) as the gold standard tool, and therefore whether or not cardiomegaly on
      CXR should be investigated further. METHODS: CXR and echocardiogram reports were
      reviewed for the presence of cardiomegaly in a population following non-ST
      segment elevation myocardial infarction (NSTEMI). Data was evaluated to determine
      whether cardiomegaly reported on CXR did indeed represent true cardiomegaly.
      Exploratory analysis was undertaken to determine whether or not Body Surface Area
      (BSA) was a significant explanatory variable. RESULTS: Data was collected for 244
      patients. Thirty-nine were reported to have cardiomegaly on CXR, 22 of those also
      had cardiomegaly on echo, giving a true positive rate of 56% and a false positive
      rate of 44%. Fifty-five were reported to have cardiomegaly on echo, of which 33
      (60%) did not have cardiomegaly identified on CXR. Sensitivity of CXR to identify
      cardiomegaly was 40% and specificity was 91% with a positive predictive value of
      56% and negative predictive value of 84%. BSA does not appear to be a significant
      explanatory variable for the discrepancy between the CXR and echo estimates of
      cardiomegaly. CONCLUSIONS: In patients following an NSTEMI, the true positive
      rate of cardiomegaly identified on CXR is not too dissimilar to the false
      positive rate, thereby suggesting that reporting "cardiomegaly" based on CXR
      findings is inaccurate and rather reporting should simply focus on the
      cardiothoracic ratio and defining this as an enlarged cardiac silhouette rather
      than true cardiomegaly. In clinical practice the data indicates that the number
      needed to investigate to identify true cardiomegaly on echo is only two, thereby
      concluding that all patients post-NSTEMI with cardiomegaly on CXR should go on to
      have an echo, consistent with current national guidelines. As the study
      population were all post-MI, further study is necessary to evaluate whether this
      association holds true in a wider population.

PMID- 29073658
TI  - Health data research in New Zealand: updating the ethical governance framework.
AB  - Demand for health data for secondary research is increasing, both in New Zealand
      and worldwide. The New Zealand government has established a large research
      database, the Integrated Data Infrastructure (IDI), which facilitates research,
      and an independent ministerial advisory group, the Data Futures Partnership
      (DFP), to engage with citizens, the private sector and non-government
      organisations (NGOs) to facilitate trusted data use and strengthen the data
      ecosystem in New Zealand. We commend these steps but argue that key strategies
      for effective health-data governance remain absent in New Zealand. In particular,
      we argue in favour of the establishment of: (1) a specialist Health and
      Disability Ethics Committee (HDEC) to review applications for secondary-use data
      research; (2) a public registry of approved secondary-use research projects
      (similar to a clinical trials registry); and (3) detailed guidelines for the
      review and approval of secondary-use data research. We present an ethical
      framework based on the values of public interest, trust and transparency to
      justify these innovations.

PMID- 29073659
TI  - Iron-pill inhalation.

PMID- 29073660
TI  - Waikato District Health Board: a trustworthy custodian of New Zealand's future
      doctors?

PMID- 29073661
TI  - New Zealand gastroenterologists' perceptions, knowledge and experience of
      exclusive enteral nutrition to treat Crohn's disease.

PMID- 29073662
TI  - Smokefree signage at New Zealand racecourses and sports facilities with outdoor
      stands.
AB  - Smokefree signage is crucial to the implementation of smokefree policies for
      outdoor venues and for facilitating smoking denormalisation. Such signage helps
      to communicate the expected norms for not smoking at venues. Therefore, we aimed
      to identify such signage at racecourses and sports facilities that had outdoor
      stands. We surveyed the entrances of 25 racecourse and 25 sport facilities with
      outdoor stands, across New Zealand. There were smokefree signs at the main
      entrances of 40% of the sports facilities with outdoor stands, and at 16% of the
      25 other entrances. None of the horse/greyhound racecourses had smokefree signage
      at any of their entrances.

PMID- 29073663
TI  - Postpartum Headache: A Prospective Study.
AB  - AIMS: To prospectively assess the incidence and etiology (ie, primary vs
      symptomatic) of headache in women during the first month postdelivery, with
      particular emphasis on the type of presentation as a clue for identifying
      potentially harmful etiologies. A secondary aim was to evaluate the relative
      frequency of migraine- vs tension-type headache in cases of primary headache.
      METHODS: A total of 900 consecutive women were enrolled in the study and examined
      within 3 days of delivery, both clinically and with transcranial color-coded
      sonography (TCCS). During the course of follow-up, all subjects presenting with
      headache suspected of being secondary to intracranial pathology underwent a
      complete clinical and instrumental assessment with TCCS and magnetic resonance
      imaging (MRI) and angiography. A telephone interview was administered to all
      subjects 1 month after delivery. Two-tailed t test, Mann-Whitney test, Pearson
      chi-square test, and multiple logistic regression were used to analyze the data.
      RESULTS: At the end of the follow-up period, 241 women (26.8% of the sample)
      reported at least one headache attack. In 88 of these 241 cases (9.8%), the
      headache attack occurred soon after delivery and was already recorded at the
      first visit. Thunderclap headache occurred in 34 (3.8%) of the subjects. In all
      but one of these subjects, the course was spontaneously benign. None of the
      recorded variables allowed discrimination of the subjects with thunderclap
      headache from those without headache. Three subjects had thunderclap headache
      following dural anesthesia, and one subject was found to have reversible cerebral
      vasoconstriction syndrome. Headache with gradual onset was recorded in 207
      subjects (23%). Three of these subjects fulfilled the criteria for pre-eclampsia,
      and 13 had postural headache after dural anesthesia. Migraine history and urinary
      protein were independent predictors of gradual onset headache, and migraine
      history and parity were significant independent predictors of pulsating pain with
      gradual onset headache. CONCLUSION: Headache appeared early in the first days
      postdelivery, and its incidence increased in the first month thereafter.
      Predictors were different according to whether the headache had a gradual onset
      or a thunderclap presentation. Primary headache accounted for the overwhelming
      majority of the recorded cases.

PMID- 29073664
TI  - Effects of Sex and Stress on Trigeminal Neuropathic Pain-Like Behavior in Rats.
AB  - AIMS: To investigate the effects and interactions of sex and stress (provoked by
      chronic restraint [RS]) on pain-like behavior in a rat model of trigeminal
      neuropathic pain. METHODS: The effects of sex and RS (carried out for 14 days as
      a model for stress) on somatosensory measures (reaction to pinprick, von Frey
      threshold) in a rat model of trigeminal neuropathic pain were examined. The study
      design was 2 * 4, with surgery (pain) and sham surgery (no pain) interacting with
      male restrained (RS) and unrestrained (nRS) rats and female RS and nRS rats. A
      total of 64 Sprague Dawley rats (32 males and 32 females) were used. Half of the
      animals in each sex group underwent RS, and the remaining half were left
      unstressed. Following the RS period, trigeminal neuropathic pain was induced by
      unilateral infraorbital nerve chronic constriction injury (IOCCI). Half of the
      animals in the RS group and half in the nRS group (both males and females) were
      exposed to IOCCI, and the remaining halves to sham surgery. Elevated plus maze
      (EPM) assessment and plasma interferon gamma (IFN-gamma) levels were used to
      measure the effects of RS. Analysis of variance (ANOVA) was used to assess the
      effects of stress, sex, and their interactions on plasma IFN-gamma levels,
      changes in body weight, EPM parameters, tactile allodynia, and
      mechanohyperalgesia. Pairwise comparisons were performed by using Tukey post hoc
      test corrected for multiple comparisons. RESULTS: Both male and female RS rats
      showed significantly altered exploratory behavior (as measured by EPM) and had
      significantly lower plasma IFN-gamma levels than nRS rats. Rats exposed to RS
      gained weight significantly slower than the nRS rats, irrespective of sex.
      Following RS but before surgery, RS rats showed significant bilateral reductions
      in von Frey thresholds and significantly increased pinprick response difference
      scores compared to nRS rats, irrespective of sex. From 17 days postsurgery,
      RSIOCCI rats showed significantly reduced von Frey thresholds and significantly
      increased pinprick response difference scores compared to nRS-IOCCI rats, and the
      von Frey thresholds were significantly lower in females than in males. RS-sham
      females-but not RS-sham males-developed persistently reduced thresholds and
      increased pinprick response difference scores. CONCLUSION: RS produced an
      increased bilateral sensitivity to stimuli applied to the vibrissal pad following
      infraorbital nerve injury, irrespective of sex. This observed sensitivity
      subsequently persisted in RS-sham female rats but not in RS-sham male rats.
      Stress induced a significant but moderate increase in pain-like behavior in
      female rats compared to male rats. RS had no significant sex effects on IFN-gamma
      levels, EPM parameters, or body weight gain. This suggests that stress may have a
      selective effect on pain-like behavior in both sexes, but the possible mechanisms
      are unclear.

PMID- 29073666
TI  - Trigeminal Neuralgia Following Lightning Injury.
AB  - Lightning and other electrical incidents are responsible for more than 300
      injuries and 100 deaths per year in the United States alone. Lightning strikes
      can cause a wide spectrum of neurologic manifestations affecting any part of the
      neuraxis through direct strikes, side flashes, touch voltage, connecting leaders,
      or acoustic shock waves. This article describes the first case of trigeminal
      neuralgia induced by lightning injury to the trigeminal nerve, thereby adding a
      new syndrome to the list of possible lightning-mediated neurologic injuries.

PMID- 29073665
TI  - An Unusual Case of Simultaneous Bilateral Trigeminal Neuralgia Due to Multiple
      Sclerosis.
AB  - Although several reports have indicated that trigeminal neuralgia related to
      multiple sclerosis may occur bilaterally in the orofacial region, trigeminal
      neuralgia pain usually involves the two sides in different time lapses, and the
      simultaneous involvement of trigeminal territories on both sides is commonly
      considered incompatible with its diagnosis. This case report describes a patient
      with bilateral trigeminal neuralgia related to multiple sclerosis that started
      simultaneously on both sides of the orofacial region. A 55-year-old man presented
      with a 16-year history of relapsing/remitting multiple sclerosis. For 1 year, the
      patient had been complaining of electric shock-like, paroxysmal pain of severe
      intensity that lasted from a fraction of a second to a few minutes and involved
      the first and second trigeminal divisions of both sides simultaneously. The
      neurophysiologic testing of trigeminal reflexes showed bilateral delayed
      latencies of reflex responses compatible with a trigeminal afferent pathway
      impairment related to multiple sclerosis. A dedicated 3T magnetic resonance
      imaging scan revealed pontine demyelinating plaque and a bilateral neurovascular
      conflict at the trigeminal root entry zone. The finding of an unusual case of
      simultaneous bilateral trigeminal neuralgia due to multiple sclerosis should
      prompt neurologists to consider a diagnosis of trigeminal neuralgia in patients
      with multiple sclerosis in cases of simultaneous involvement of trigeminal
      territories on both sides.

PMID- 29073667
TI  - Clinical Characteristics, Pain, and Quality of Life Experiences of Trigeminal
      Neuralgia in a Multi-Ethnic Asian Cohort.
AB  - AIMS: To describe the clinical characteristics of trigeminal neuralgia (TN) in a
      multi-ethnic Malaysian population and to relate them to standardized measures of
      pain severity, anxiety, depression, and quality of life (QoL). METHODS: Patients
      fulfilling the International Headache Society (IHS) criteria for TN were
      prospectively interviewed for their demographic and clinical data. Pain intensity
      was rated with a visual analog scale (VAS), anxiety and depression were
      determined by the Hospital Anxiety and Depression Scale (HADS), and QoL was
      assessed by the Short-Form 36 (SF-36) questionnaire. Chi-square, Mann-Whitney U,
      and Spearman correlation tests were used to test for differences considering a
      significance level of P < .05. RESULTS: Of the 75 included patients, 52 (69.3%)
      were women with a mean +/- standard deviation (SD) onset age of 52.0 +/- 12.7
      years, and 57.3% were Chinese, 24.0% Malay, and 18.7% Indian. Pain was more
      common on the right side (69.3%) and in the maxillary and mandibular divisions.
      VAS scores for pain at its worst were higher in anxious/borderline anxious
      patients compared to non-anxious patients (89.5 +/- 15.9 vs 80.9 +/- 17.2,
      respectively; P < .05), and VAS scores for pain at its least were higher in
      depressed/borderline depressed subjects compared to non-depressed subjects (38.4
      +/- 25.8 vs 23.0 +/- 19.2, respectively; P < .05). Chinese patients had lower VAS
      scores for pain at its least compared to Indian patients (19.7 +/- 16.1 vs 39.9
      +/- 24.7; P < .01). TN patients scored lower in all eight domains of the SF-36
      compared to the general population. Indian patients had lower scores in role
      limitations due to physical health (8.9 +/- 23.2 vs 49.4 +/- 43.8; P < .01) and
      social function (56.3 +/- 13.6 vs 76.5 +/- 23.6; P < .01) than Chinese patients,
      and Malay patients had lower mental health scores compared to Chinese patients
      (59.1 +/- 19.5 vs 73.0 +/- 21.0; P < .01). CONCLUSION: Clinical characteristics
      of TN patients were similar to those of other populations. There were differences
      in pain ratings and QoL between TN patients of different ethnicities, as well as
      between those with anxiety and depression.

PMID- 29073668
TI  - Congenital Epidermoid Cyst Presenting as Isolated Painful Trigeminal Neuropathy:
      Indications for Neuroimaging in the Diagnostic Process.
AB  - This article reports a case of a cerebellopontine angle epidermoid cyst
      presenting as isolated painful trigeminal neuropathy. The indolent nature of
      these uncommon benign tumors leads to frequent delays in their presentation and
      diagnosis, with patients often initially undergoing dental procedures. This is
      illustrated in the present case reported here, which highlights the difficulties
      in identifying trigeminal neuralgia (TN), particularly in its early phases, and
      supports current recommendations for routine neuroimaging in suspected cases of
      painful trigeminal neuropathy, which, unlike classic TN, is caused by a disorder
      other than neurovascular compression (even in the absence of additional
      neurologic symptoms or signs) and is present particularly in younger patients
      with atypical features. Additionally, this case report offers a unique patient
      perspective of living with TN, with a detailed description by one of the authors
      of the nature of the pain and its impact.

PMID- 29073669
TI  - Prevalence of Temporomandibular Disorders in Rheumatoid Arthritis and Associated
      Risk Factors: A Nationwide Study in Taiwan.
AB  - AIMS: To investigate the association between temporomandibular disorders (TMD)
      and rheumatoid arthritis (RA), as well as potential risk factors for TMD and the
      preventive effect of medications on TMD, by using the Taiwan National Health
      Insurance Research Database. METHODS: In total, 17,317 patients newly diagnosed
      with RA and 17,317 matched controls without RA were followed up from 2000 to
      2010. Cox regression was used to determine risk factors for developing TMD.
      Kaplan-Meier curve with log-rank test was used to determine the cumulative risk
      of TMD in RA patients and the effects of antirheumatic medications. RESULTS: Cox
      regression showed a higher risk of developing TMD if patients had RA (adjusted
      hazard ratio [HR] 2.538, P < .001) and a lower risk if patients were of male
      gender and elderly (>= 40 years) in comparison to younger patients (20 to 29
      years) (P < .01). Patients with insomnia, stroke, and mental disorders had,
      respectively, 4.756, 6.929, and 9.671 times the number of events of TMD compared
      to those without diseases (P < .001). No patients with RA treated with disease
      modifying antirheumatic drugs (DMARDs) developed TMD after the 11-year follow-up.
      CONCLUSION: RA patients had 2.538 times the events of TMD compared with non-RA
      patients during this trial in Taiwan. The other risk factors for developing TMD
      included female gender, younger age, insomnia, stroke, and mental disorders. The
      DMARDs had a beneficial effect on prevention of TMD.

PMID- 29073670
TI  - Differential Effect of Articaine on Sarcoendoplasmic Reticulum Calcium Adenosine
      Triphosphatase of Medial Pterygoid Muscle.
AB  - AIMS: To determine the effect of articaine on sarcoendoplasmic reticulum calcium
      adenosine triphosphatase (SERCA) isoforms of the medial pterygoid muscle.
      METHODS: Native SERCA from the medial pterygoid muscles of 24 rabbits was
      isolated by ultracentrifugation, and its isoforms were purified by chromatography
      and assessed by enzyme-linked immunosorbent assay (ELISA). SERCA activity and
      calcium transport capability were determined by using colorimetric and
      radioisotopic methods. The mean +/- standard deviation (SD) half maximal
      inhibitory concentration (IC50) of articaine was determined for each isoform, and
      these values were compared by using analysis of variance (ANOVA) (P < .05).
      RESULTS: The native SERCA preparation consisted of 34% SERCA1a, 53% SERCA2a, 10%
      SERCA2b, and 3% combined SERCA3 and SERCA1b. Articaine caused inhibition of
      activity and calcium uptake in the native SERCA preparation and in each of the
      purified isoforms. The IC50 (mM) values for enzymatic activity were: SERCA1a 22.0
      +/- 2.3 > SERCA2a 16.4 +/- 2.4 > SERCA2b 11.3 +/- 1.9, and 15.1 +/- 2.1 for
      native SERCA. For calcium transport, IC50 values were: SERCA1a 31.1 +/- 3.3 >
      SERCA2a 24.8 +/- 1.8 > SERCA2b 21.5 +/- 1.5, and 25.2 +/- 3.2 for native SERCA.
      IC50 values for inhibition of enzymatic activity were significantly different
      among the purified isoforms, but only the value obtained for SERCA1a was
      significantly different compared to native SERCA. For inhibition of calcium
      transport, IC50 values for both SERCA2a and SERCA2b differed significantly
      compared to SERCA1a, and the value for SERCA1a was significantly different
      compared to native SERCA. The most articaine-sensitive isoform was SERCA2b, and
      the native preparation showed sensitivity similar to SERCA2a. CONCLUSION: The
      differential inhibition of articaine on medial pterygoid SERCA isoforms is
      evident at concentrations lower than used in current dental practice (125 mM) and
      accounts for anesthetic myotoxicity. Muscle relaxation likely becomes impaired as
      a result of increased calcium levels in the myoplasm due to the decreased
      activity and calcium transport caused by the inhibition of SERCA.

PMID- 29073675
TI  - Iris L. Romero, MD, MS.

PMID- 29073676
TI  - Obstetrics and Gynecology: A Specialty at the Forefront of Care for LGBTQ
      Patients.

PMID- 29073677
TI  - Establishing Effective Health Care Partnerships with Sexual and Gender Minority
      Patients: Recommendations for Obstetrician Gynecologists.

PMID- 29073678
TI  - Family Building by Same-Sex Male Couples via Gestational Surrogacy.

PMID- 29073679
TI  - Co-IVF for Same-Sex Female Couples.

PMID- 29073680
TI  - Lesbian Pregnancy: Care and Considerations.
AB  - The constructs and the provision of preconception and obstetrical care have
      historically been based on the assumption of heterosexuality, and have often
      excluded lesbian women. However, due to significant strides in lesbian, gay,
      bisexual, transgender, and queer (LGBTQ) civil rights, more lesbian women desire
      to create and expand their families, and lesbian parented families are
      increasing. This places obstetrical care providers at the forefront of the
      movement to build inclusive health care environments. Therefore, it is incumbent
      upon those of us who work in obstetrics to understand, recognize, and respect the
      unique cultural considerations that pertain to lesbian women and couples seeking
      parenthood. This review seeks to provide culturally sensitive guidance on the
      specific concerns and challenges lesbians face, from preconception care to
      postpartum care, and briefly addresses legal issues and considerations for the
      nonbiologic mother. The recommendations outlined here are drawn from studies of
      the experiences of lesbian women with pregnancy. However, the scientific
      literature is very limited, and there is a clear need for additional obstetrical
      research focused on this patient group. As professionals committed to assuring
      optimal outcomes for all obstetrical patients, it is crucial that we promote the
      inclusion of sexual minority women in our clinical practices and research
      endeavors.

PMID- 29073681
TI  - Preventive Health for Transgender Men and Women.

PMID- 29073682
TI  - Breast Cancer Screening, Management, and a Review of Case Study Literature in
      Transgender Populations.

PMID- 29073683
TI  - Update on Gender-Affirming Treatment for the Transgender Woman.

PMID- 29073684
TI  - Sexual Dysfunction in Lesbian Women: A Systematic Review of the Literature.

PMID- 29073686
TI  - [Not Available].

PMID- 29073687
TI  - [Interdisciplinary Simulation of Emergency Caesarean Section to Improve
      Subjective Competence].
AB  - The emergency caesaran section is a gynecological emergency situation which is
      potentially life-threatening for mother and child. In the management of these
      time-critical situations human factors as well as the competence of the crisis
      resource management team have been shown to be important factors for success. The
      concept "simulation" has not been validated as a training tool for professional
      competence of multidisciplinary teams in the delivery suite. The aim of this
      study was, to assess the competence gain by subjective evaluation of the team
      members after taking part in an emergency caesarian section training which is
      integrable into the daily clinic setting. Method 36 members of a
      multidisciplinary team of a delivery suite took part in a 4-hourly "high
      fidelity" simulation training "emergency caesarian section". Scenarios were
      created around the case setting of eclampsia with bradycardia of the child,
      uterus rupture, placenta abruption and cord prolapse. Each participant was
      involved in 2 scenarios as either a spectator or a team member. Using a
      questionnaire, the course performance and debriefing were evaluated and the
      subjective professional competence in Crisis Resource Management were recorded.
      Results  In the collective of the trainee (over/equal 5 years), 25% had no
      experience in any cases of emergency caesarean in practice. On a scale of 1 to 6
      (1=very good, 6=fail) the course was given an overall mark of 1.4 and a mark of
      1.8 for its relevance to daily work. 6 months after the training, participants
      rated their competencies in prioritising necessary actions, following treatment
      plans, communicating among the team members as well as integrating new
      information as significantly improved. Conclusion  The 4-hour simulation training
      can be easily integrated into everyday clinical practice. The participants marked
      the course scenarios as realistic and relevant for their clinical practice. The
      number of years of prior work experience is not significanty related with the
      experience in rare emergency situations. The interdisciplinary team training is a
      way to improve individual performance as well as to establish and practise
      interdisciplinary emergency concepts.

PMID- 29073688
TI  - [Does a Higher Ambient Temperature in the Delivery Room Prevent Hypothermia in
      Preterm Infants <1500 g?]
AB  - : Aim Because hypothermia in the preterm infant immediately after delivery can
      cause an increase in morbidity and mortality in the newborn period, one of the
      most important goals is preventing hypothermia in preterm infants. There is
      sufficient data on prevention methods such as warming respirator gas, radiant
      heat sources, warmed blankets, sterile polyethylene bags, etc. However no general
      recommendation of the optimal environmental temperature in the delivery room
      exists. Methods We compared the rectal body temperature of VLBW infants on
      admission to the NICU, born in delivery rooms with an ambient temperature of 28
      degrees C vs. 34 degrees C. STUDY DESIGN: retrospective cohort study. Results The
      higher ambient temperature in the delivery room results in a lower number of VLBW
      infants with hypothermia on admission (body temperature <36.5 degrees C), but
      also an increase in hyperthermic (body temperature >37.5 degrees C) preterm
      babies. Conclusion A higher ambient temperature in the delivery room may also
      prevent hypothermia in preterm infants in addition to the above-mentioned methods
      to stabilize body temperature in VLBW infants. Further studies are essential to
      confirm these results and hence recommend an ideal temperature in the delivery
      room.

PMID- 29073685
TI  - Family Planning for Sexual Minority Women.

PMID- 29073689
TI  - Cesarean Delivery in a Case of Persistent Second Trimester Ovarian
      Hyperstimulation Syndrome.
AB  - Background Ovarian hyperstimulation syndrome develops as an iatrogenic
      complication related to ovulation induction. It is usually self-limiting with
      complete resolution expected within 10-14 days. Case The current case is a report
      of an unusually prolonged course of ovarian hyperstimulation syndrome persisting
      until 22 weeks of gestation, accidentally discovered and managed by cesarean
      section due to an obstetric indication. Conclusion Clinicians should be aware of
      this possibility when managing cases of IVF pregnancy.

PMID- 29073690
TI  - Fetal Valproate Syndrome - Still a Problem Today!
AB  - Introduction Fetal exposition to valproate can lead to a cluster of facial
      dysmorphism, congenital anomalies and neurodevelopmental retardation. Case Report
      In this report we describe 2 cases of fetal valproate syndrome. In the first
      case, the gravida had a valproate medication before and during pregnancy with
      additional folic acid. She delivered a male premature infant at 25+2 weeks of
      gestation due to preterm labor and rupture of the membranes. Physical examination
      showed even in the premature infant typical signs of fetal valproate syndrome
      with trigonocephaly, epicanthal folds, broad root of the nose, low-set ears, thin
      upper lip and anteverted nares. In the second case, the gravida was under
      antiepileptic therapy with valproate and lamotrigine before and during pregnancy
      without any prophylaxis with folic acid. Sonographic examination during pregnancy
      diagnosed a spina bifida, Chiari II malformation and clubfeet. A female newborn
      was delivered at 39+4 weeks of gestation. Besides the prenatally detected
      anomalies, facial dysmorphism including microcephaly, low-set ears, thin upper
      lip and shallow philtrum were seen after birth. Conclusion Valproate, a widely
      used anticonvulsant medication, is known for its teratogenic effects. The risk of
      congenital anomalies is even higher in combination with other antiepileptic
      drugs. Therefore, the avoidance of valproate or at least supplementation with a
      high dose prophylactic folic acid before and during pregnancy is highly
      recommended for women with epilepsy.

PMID- 29073691
TI  - ?

PMID- 29073692
TI  - Video Comment on Rupam Bhattacharyya et al.

PMID- 29073693
TI  - To cuff or not to cuff: that is the question!

PMID- 29073694
TI  - To play or not to play - with the adenoma detection rate.

PMID- 29073695
TI  - Colorectal cancer screening: with pain, no gain.

PMID- 29073696
TI  - Adherence to quality indicators of Barrett's esophagus surveillance: where do we
      stand?

PMID- 29073697
TI  - Experienced endoscopists improve Barrett's surveillance outcomes independently of
      time allocation.

PMID- 29073698
TI  - Reply to Westerveld et al. and Schembri et al.

PMID- 29073699
TI  - Severe submucosal fibrosis - the "Achilles' heel" of peroral endoscopic myotomy.

PMID- 29073700
TI  - Reply to Nabi et al.

PMID- 29073701
TI  - Re-purposed use of a stiffening wire as a novel adjunct for direct cholangioscopy
      access.

PMID- 29073702
TI  - Reply to Zimmer.

PMID- 29073703
TI  - [French comment on article Probe-based endomicroscopy for in vivo detection of
      gastric intestinal metaplasia and neoplasia: a multicenter randomized controlled
      trial].

PMID- 29073705
TI  - [French comment on article Endocuff-assisted colonoscopy is associated with a
      lower adenoma miss rate: a multicenter randomized tandem study].

PMID- 29073704
TI  - [French comment on article Endocuff-assisted vs. standard colonoscopy in the
      fecal occult blood test-based UK Bowel Cancer Screening Programme (E-cap study):
      a randomized trial].

PMID- 29073706
TI  - [French comment on article Higher adenoma detection rate with the endocuff: a
      randomized trial].

PMID- 29073707
TI  - [French comment on article Acceptability of two colorectal cancer screening
      tests: pain as a key determinant in sigmoidoscopy].

PMID- 29073709
TI  - ?

PMID- 29073708
TI  - [Rare Perirenal Masses: What Radiologists Should Know about them].

PMID- 29073710
TI  - ?

PMID- 29073711
TI  - ?

PMID- 29073712
TI  - ?

PMID- 29073713
TI  - ?

PMID- 29073714
TI  - ?

PMID- 29073715
TI  - ?

PMID- 29073716
TI  - Antitumor activity of Lepidium latifolium and identification of the
      epithionitrile 1-cyano-2,3-epithiopropane as its major active component.
AB  - Consumption of Brassica (Cruciferae) vegetables is associated with a reduced risk
      of cancer, but identification of the active components and insights into the
      underlying molecular events are scarce. Here we found that an extract of Lepidium
      latifolium, a cruciferous plant native to southern Europe, Mediterranean
      countries and Asia, showed in vitro cytotoxic activity, inducing caspase
      dependent apoptosis, in a variety of human tumor cells, and the plant juice
      showed in vivo antitumor activity in a HT-29 human colon cancer xenograft mouse
      model. The epithionitrile 1-cyano-2,3-epithiopropane (CETP) was identified as the
      major active cancer cell-killing principle of L. latifolium. Synthetic and plant
      derived CETP displayed similar proapoptotic activities as assessed by biochemical
      and morphological analyses. Analysis of the antiproliferative capacity of CETP on
      a wide number of cancer cell lines from the NCI-60 cell line panel followed by
      COMPARE analysis, showed an activity profile different from known anticancer
      agents. Flow cytometry and biochemical analyses revealed that CETP-induced
      apoptosis involved mitochondria, as assessed by loss of mitochondrial
      transmembrane potential and generation of reactive oxygen species, while
      overexpression of Bcl-XL and Bcl-2 prevented CETP-induced apoptosis. Inhibition
      of reactive oxygen species by glutathione and N-acetyl cysteine reduced the
      apoptotic response induced by CETP. FADD dominant negative form, blocking
      Fas/CD95 signaling, and a specific caspase-8 inhibitor also inhibited CETP
      induced killing. Taken together, our data suggest that the cancer cell-killing
      action of CETP, involving both intrinsic and extrinsic apoptotic signaling
      pathways, underlies the antitumor activity of L. latifolium plant, which could be
      of potential interest in cancer treatment.

PMID- 29073717
TI  - Effective excision of cutaneous squamous cell carcinoma of the face using
      analysis of intra-operative frozen sections from the whole specimen.
AB  - BACKGROUND AND OBJECTIVES: We excised cutaneous squamous cell carcinoma (cSCC) of
      the face while using intra-operative frozen section analysis of the margins in an
      optimized bread-loafing fashion (WIFSA). METHODS: Medical records were reviewed
      of 160 cSCCs of the face that were treated by surgical excision with WIFSA
      between April 2007 and January 2013. The accuracy of WIFSA was verified by
      comparing results with postoperative formalin-fixed paraffin-embedded (FFPE)
      sections. Also, recurrence and metastasis during follow-up were studied and
      duration of treatment and complications were analyzed. RESULTS: The 160 cSCCs
      affected 152 patients. In 131 cSCCs (mean follow-up: 41.0 months, SD: +/-26.3,
      range: 3.0-110.7) occurred 6 (4.6%) recurrences and 2 (1.5%) metastases. Of the
      WIFSA results, 98.8% corresponded with postoperative FFPE sections. Mean duration
      of treatment was 77 min (SD: +/-25, range: 34-159) and complication rate was
      8.1%. CONCLUSIONS: Surgical excision with WIFSA is an excellent treatment
      modality for cSCC of the face because of its accurate method for assessment of
      complete tumor removal, low recurrence and metastasis rate, short average
      duration of treatment, and low complication rate.

PMID- 29073718
TI  - Evaluation of a new method for librarian-mediated literature searches for
      systematic reviews.
AB  - : To evaluate and validate the time of completion and results of a new method of
      searching for systematic reviews, the exhaustive search method (ESM), using a
      pragmatic comparison. METHODS: Single-line search strategies were prepared in a
      text document. Term completeness was ensured with a novel optimization technique.
      Macros in MS Word converted the syntaxes between databases and interfaces almost
      automatically. We compared search characteristics, such as number of search terms
      and databases, and outcomes, such as number of included and retrieved references
      and precision, from ESM searches and other Dutch academic hospitals identified by
      searching PubMed for systematic reviews published between 2014 and 2016. We
      compared time to perform the ESM with a secondary comparator of recorded search
      times from published literature and contact with authors to acquire unpublished
      data. RESULTS: We identified 73 published Erasmus MC systematic reviews and 258
      published by other Dutch academic hospitals meeting our criteria. We pooled
      search time data from 204 other systematic reviews. The ESM searches differed by
      using 2 times more databases, retrieving 44% more references, including 20% more
      studies in the final systematic review, but the time needed for the search was 8%
      of that of the control group. Similarities between methods include precision and
      the number of search terms. CONCLUSIONS: The evaluated similarities and
      differences suggest that the ESM is a highly efficient way to locate more
      references meeting the specified selection criteria in systematic reviews than
      traditional search methods. Further prospective research is required.

PMID- 29073719
TI  - Value of whole breast magnetic resonance elastography added to MRI for lesion
      characterization.
AB  - The purpose of this work was to assess the diagnostic value of magnetic resonance
      elastography (MRE) in addition to MRI to differentiate malignant from benign
      breast tumors, and the feasibility of performing MRE on the whole breast. MRE
      quantified biomechanical properties within the entire breast (50 slices) using an
      11 min acquisition protocol at an isotropic image acquisition resolution of 2 * 2
      * 2 mm3 . Fifty patients were included. Finally, 43 patients (median age 52) with
      a suspect breast lesion detected by mammography and/or ultrasound were examined
      by MRI and MRE at 1.5 T. The viscoelastic parameters, i.e. elasticity (Gd ),
      viscosity (Gl ), the magnitude of the complex shear modulus Gd2+Gl2, and the
      phase angle y=2piatanGlGd, were measured via MRE and correlated with MRI Breast
      Imaging-Reporting and Data System (BI-RADS) score, histological type, and
      histological grade. Stroma component and angiogenesis were also correlated with
      viscoelastic properties. In the 43 lesions, Gd decreased and y increased with the
      MRI BI-RADS score (pGd  = 0.02, py  = 0.002), whereas (Gl ) and y were increased
      in malignant lesions (pGl  = 0.045, py  = 0.0004). The area under the curve
      increased from 0.84 for MRI BI-RADS alone to 0.92 with the MRI BI-RADS and y (AUC
      increase +0.08; 95% CI (-0.003; 0.16)). Lesion characterization using the y
      parameter increased the diagnostic accuracy. The phase angle y was found to have
      a significant role (p = 0.01) in predicting malignancy independently of the MRI
      BI-RADS. Interestingly, histological analysis showed no correlation between
      viscoelastic parameters and percentage and type of stroma, CD34 quantification of
      vessels, or histological grade. The combination of MRE and MRI improves the
      diagnostic accuracy for breast lesions in the studied cohort. In particular, the
      phase angle y was found to have a significant role in predicting malignancy in
      addition to BI-RADS.

PMID- 29073720
TI  - MALAT1 modulates the autophagy of retinoblastoma cell through miR-124-mediated
      stx17 regulation.
AB  - The retinoblastoma is the most common intraocular malignant tumor in infants and
      children; it is one of the deadliest forms of cancer due to its limited
      sensitivity to chemotherapy and radiotherapy. In several cancers, chemoresistance
      is associated with autophagy induction. Non-coding RNAs, including long non
      coding RNAs (lncRNA) and microRNAs (miRNAs) have been reported to regulate
      physiological activities of the cells, including proliferation, apoptosis,
      migration, as well as autophagy. MALAT1, a well-established lncRNA acts as an
      oncogene, promotes cancer proliferation, and metastasis via the stimulation of
      autophagy. In addition to MALAT1, miR-124, a known tumor suppressor, has also
      been reported to regulate cell apoptosis and autophagy in dopaminergic neurons.
      In the present study, we investigated the roles of MALAT1 and miR-124 in the
      regulation of retinoblastoma cell autophagy through evaluating the changes of
      autophagy-related proteins. Through direct targeting miR-124, MALAT1 promotes
      retinoblastoma cell autophagy. Further, we investigated whether Syntaxin 17
      (STX17), a Soluble NSF Attachment Protein receptor (SNARE) of the autophagosome,
      is involved in MALAT1/miR-124 regulation of retinoblastoma cell autophagy, and
      the underlying mechanism. Taken together, we provided novel experimental and
      theoretical basis for regulation of retinoblastoma cell autophagy, and potential
      direction of dealing with autophagy-induced chemoresistance of retinoblastoma,
      which need further in-depth study.

PMID- 29073721
TI  - MicroRNA-381-induced down-regulation of CXCR4 promotes the proliferation of renal
      tubular epithelial cells in rat models of renal ischemia reperfusion injury.
AB  - This study aims to explore whether microRNA-381 (miR-381) mediating CXCR4 affects
      the renal tubular epithelial cells (RTEC) of renal ischemia reperfusion (I/R)
      injury. Forty-eight rats were assigned into the I/R (n = 24, successfully
      established as I/R model) and sham (n = 24) groups. After collecting kidney
      tissues, immunohistochemistry, and microvascular density (MVD) counting were
      conducted for CXCR4 positive expression and MVD numbers. RTECs were assigned into
      the sham, blank, negative control (NC), miR-381 mimics, miR-381 inhibitor, si
      CXCR4, and miR-381 inhibitor + si-CXCR4 groups. RT-qPCR and Western blotting were
      performed for relative expressions in tissues and cells. Cell proliferation and
      apoptosis were measured by MTT assay and flow cytometry. Results showed that
      compared with the sham group, positive expression of CXCR4 and MVD number were
      higher in the I/R group, which exhibited decreased miR-381 and increased
      expression of CXCR4, stromal cell-derived factor-1 (SDF1), vascular endothelial
      growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1alpha) and Tie-2. Dual
      luciferase reporter gene assay verified that CXCR4 is a target gene of miR-381.
      MiR-381 expression was lower in the miR-381 inhibitor + si-CXCR4 and miR-381
      inhibitor groups and higher in the miR-381 mimics group than the blank and NC
      groups. Compared with the blank and NC groups, the miR-381 mimics and si-CXCR4
      groups exhibited higher cell proliferation but lower cell apoptosis and
      expression of CXCR4, SDF1, VEGF, HIF-1alpha, and Tie-2, whereas the miR-381
      inhibitor group exhibited the opposite trend. In conclusion, miR-381 may promote
      RTEC proliferation in rats with renal I/R injury by down-regulating CXCR4.

PMID- 29073722
TI  - Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma.
AB  - The benefits of inhibiting autophagy in cancer are still controversial, with
      differences in outcome based on the type of tumor, the context and the particular
      stage of inhibition. Here, we investigated the impact of inhibiting autophagy at
      different stages on chemosensitivity using 3-dimensional (3D) models of
      mesothelioma, including ex vivo human tumor fragment spheroids. As shown by LC3B
      accumulation, we successfully inhibited autophagy using either an early stage
      ULK1/2 inhibitor (MRT 68921) or a late stage inhibitor (hydroxychloroquine). We
      found that inhibition of autophagy at the early stage, but not at late stage,
      potentiated chemosensitivity. This effect was seen only in those spheroids with
      high autophagy and active initiation at steady state. Inhibition of autophagy
      alone, at either early or late stage, did not cause cell death, showing that the
      inhibitors were non-toxic and that mesothelioma did not depend on autophagy at
      baseline, at least over 24 h. Using ATG13 puncta analysis, we found that
      autophagy initiation identified tumors that are more chemosensitive at baseline
      and after autophagy inhibition. Our results highlight a potential role of
      autophagy initiation in supporting mesothelioma cells during chemotherapy. Our
      work also highlights the importance of testing the inhibition of different stages
      in order to uncover the role of autophagy and the potential of its modulation in
      the treatment of cancer.

PMID- 29073723
TI  - BMP9/COX-2 axial mediates high phosphate-induced calcification in vascular smooth
      muscle cells via Wnt/beta-catenin pathway.
AB  - Vascular calcification is a notable risk factor for cardiovascular system. High
      phosphate can induce calcification in vascular smooth muscle cells (VSMCs), but
      the detail mechanism underlying this process remains unclear. In the present
      study, we determined the relationship between high phosphate and bone
      morphogenetic protein 9 (BMP9) in VSMCs, the effect of BMP9 on calcification in
      VSMCs and the effect of COX-2 on BMP9 induced calcification in VSMCs, as well as
      the possible mechanism underlying this biological process. We found that high
      phosphate obviously up-regulates the expression of BMP9 in VSMCs. Over-expression
      of BMP9 decreases the level of alpha-smooth muscle cell actin (alpha-SMA)
      apparently, but increases the level of Runx-2, Dlx-5, and ALP in VSMCs.
      Meanwhile, BMP9 increases the level of OPN and OCN, promotes mineralization in
      VSMCs and induces calcification in thoracic aorta. High phosphate and over
      expression of BMP9 increases the level of COX-2. Over-expression of COX-2
      enhances the inhibitory effect of BMP9 on alpha-SAM and increases the level of
      OPN and OCN induced by BMP9. However, inhibition of COX-2 decreases the BMP9
      induced calcification in VSMCs and thoracic aorta. For mechanism, we found that
      high phosphate or BMP9 increases the level of beta-catenin and p-GSK3beta in
      VSMCs, but no substantial effect on GSK3beta. However, COX-2 inhibitor decreases
      the expression of beta-catenin induced by BMP9. Our findings indicated that BMP9
      is involved in the phosphate-induced calcification in VSMCs and COX-2 partly
      mediates the BMP9-induced calcification in VSMCs through activating Wnt/beta
      catenin pathway.

PMID- 29073725
TI  - Radiomics in paediatric neuro-oncology: A multicentre study on MRI texture
      analysis.
AB  - Brain tumours are the most common solid cancers in children in the UK and are the
      most common cause of cancer deaths in this age group. Despite current advances in
      MRI, non-invasive diagnosis of paediatric brain tumours has yet to find its way
      into routine clinical practice. Radiomics, the high-throughput extraction and
      analysis of quantitative image features (e.g. texture), offers potential
      solutions for tumour characterization and decision support. In the search for
      diagnostic oncological markers, the primary aim of this work was to study the
      application of MRI texture analysis (TA) for the classification of paediatric
      brain tumours. A multicentre study was carried out, within a supervised
      classification framework, on clinical MR images, and a support vector machine
      (SVM) was trained with 3D textural attributes obtained from conventional MRI. To
      determine the cross-centre transferability of TA, an assessment of how SVM
      performs on unseen datasets was carried out through rigorous pairwise testing.
      The study also investigated the nature of features that are most likely to train
      classifiers that can generalize well with the data. Finally, the issue of class
      imbalance, which arises due to some tumour types being more common than others,
      was explored. For each of the tests carried out through pairwise testing, the
      optimal area under the receiver operating characteristic curve ranged between 76%
      and 86%, suggesting that the model was able to capture transferable tumour
      information. Feature selection results suggest that similar aspects of tumour
      texture are enhanced by MR images obtained at different hospitals. Our results
      also suggest that the availability of equally represented classes has enabled SVM
      to better characterize the data points. The findings of the study presented here
      support the use of 3D TA on conventional MR images to aid diagnostic
      classification of paediatric brain tumours.

PMID- 29073726
TI  - Reconstruction of extensive thoracic wall defect using the external oblique
      myocutaneous flap: An analysis on 20 Chinese patients with locally advanced soft
      tissue sarcoma.
AB  - BACKGROUND: Soft tissue sarcomas are rare neoplasms that can occur in the
      thoracic wall, abdominal wall, extremities, and inguinal region. Wide local
      resection, with precise histological margin control, results in large skin
      defects that are challenging to close. Various repair procedures, such as
      vertical rectus abdominis flaps (VRAM), latissimus dorsi flaps, and tensor fascia
      lata (TFL) flaps are used to cover broad thoracic wall defects. Although the
      cosmetic reconstruction results of using these flaps are often excellent, each
      has significant drawbacks. The external oblique musculocutaneous flap is a simple
      and safe surgical procedure for covering thoracic wall defects. OBJECTIVE: This
      study aimed to retrospectively assess the safety and technique of using the
      external oblique musculocutaneous flap to cover large thoracic wall defects after
      radical excision of locally advanced sarcomas in 20 patients at a single
      institution. METHOD: From January 2006 to December 2016, 20 Chinese patients with
      large advanced sarcomas on their trunks received wide local resection, with
      precise histological negative margins. The external oblique musculocutaneous
      flap, mobilized from the ipsilateral abdominal wall, was harvested to cover broad
      thoracic wall defects. RESULTS: Among the 20 sarcoma patients (12 females and 8
      males, ranging in age from 25 to 73 years), there were five patients with primary
      tumors and 15 patients with recurrent tumors. The median tumor diameter was
      approximately 15.3 cm. After excising the lesion, the median time to cover the
      defect with the external oblique myocutaneous flap was 66 min. The average blood
      loss when harvesting the flap was approximately 48 mL. For the 20 patients in our
      cohort, the external oblique flap achieved closure of defects measuring an
      average area of 256 cm2 . No other flaps or reconstruction techniques were used
      to cover the large defects in this study. There were no deaths directly related
      to the flap reconstruction procedures. CONCLUSION: The external oblique
      musculocutaneous flap was a safe and reliable method of covering broad thoracic
      wall defects after radical tumor excision.

PMID- 29073724
TI  - Interleaved 31 P MRS imaging of human frontal and occipital lobes using dual RF
      coils in combination with single-channel transmitter-receiver and dynamic B0
      shimming.
AB  - In vivo 31 P magnetic resonance spectroscopy (MRS) provides a unique tool for the
      non-invasive study of brain energy metabolism and mitochondrial function. The
      assessment of bioenergetic impairment in different brain regions is essential to
      understand the pathophysiology and progression of human brain diseases. This
      article presents a simple and effective approach which allows the interleaved
      measurement of 31 P spectra and imaging from two distinct human brain regions of
      interest with dynamic B0 shimming capability. A transistor-transistor logic
      controller was employed to actively switch the single-channel X-nuclear
      radiofrequency (RF) transmitter-receiver between two 31 P RF surface coils,
      enabling the interleaved acquisition of two 31 P free induction decays (FIDs)
      from human occipital and frontal lobes within the same repetition time. Linear
      gradients were incorporated into the RF pulse sequence to perform the first-order
      dynamic shimming to further improve spectral resolution. The overall results
      demonstrate that the approach provides a cost-effective and time-efficient
      solution for reliable 31 P MRS measurement of cerebral phosphate metabolites and
      adenosine triphosphate (ATP) metabolic fluxes from two human brain regions with
      high detection sensitivity and spectral quality at 7 T. The same design concept
      can be extended to acquire multiple spectra from more than two brain regions or
      can be employed for other magnetic resonance applications beyond the 31 P spin.

PMID- 29073727
TI  - Mouse double minute 4 variants modify susceptibility to risk of recurrence in
      patients with squamous cell carcinoma of the oropharynx.
AB  - Given the crucial role of Mouse double minute 4 (MDM4) oncoprotein in p53
      pathway, single nucleotide polymorphisms (SNPs) could serve as such biomarkers
      for prediction of SCCOP recurrence. Thus, we investigated associations between
      three tagging putatively functional variants of MDM4, two in the 3' untranslated
      region of 3' UTR [rs11801299 (NC_000001.10:g.204529084G>A) and
      rs10900598(NC_000001.10:g.204525568G>T)] and one in intron 1
      [rs1380576(NC_000001.10:g.204488278G>C)], and recurrence risk of SCCOP in 1,008
      incident patients. A log-rank test and multivariable Cox models were used to
      assess associations. Patients with MDM4-rs10900598 GT/TT had a worse disease-free
      survival (DFS) compared with corresponding GG genotype, while those with
      rs11801299 AG/AA genotypes had a lower recurrence risk than the cases with
      rs11801299 GG genotype (both log-rank, P < 0.001). Multivariable analysis showed
      that significantly different recurrence risk were found among patients with MDM4
      rs10900598 GT/TT and rs11801299 AG/AA variant genotypes (HR, 2.0, 95% CI, 1.4-2.9
      and HR, 0.4, 95% CI, 0.3-0.6, respectively) compared with their corresponding
      common homozygous genotypes. Furthermore, after combining the risk genotypes of
      the three SNPs, patients among low-risk group had a significantly lower risk of
      SCCOP recurrence than those in high-risk group (HR, 0.2, 95% CI, 0.1-0.3). The
      risk for both individual SNPs or combined risk genotypes was restricted to HPV
      positive SCCOP patients. Our findings suggest that the MDM4 polymorphisms may,
      individually or in combination, confer an independent risk of SCCOP recurrence,
      particularly in HPV-positive SCCOP patients. However, larger studies are needed
      to validate our findings.

PMID- 29073728
TI  - HOXA3 promotes tumor growth of human colon cancer through activating
      EGFR/Ras/Raf/MEK/ERK signaling pathway.
AB  - Homeobox A3 (HOXA3), one of HOX transcription factors, regulates gene expression
      during embryonic development. HOXA3 expression has been reported to be associated
      with several cancers; however, its role in colon cancer and underlying mechanism
      are still unclear. The expression of HOXA3 in 232 paired of human colon tumor and
      adjacent non-tumorous tissues were measured by qPCR. The relationship between
      HOXA3 expression and clinical outcomes were analyzed by Kaplan-Meier survival
      curves analysis. Human colon cancer cell lines HT29 and HTC116 were transfected
      with HOXA3 siRNA, or HOXA3 expressing vector, and then cell proliferation and
      apoptosis were assessed, respectively. Western blot was performed to detect the
      activation of EGFR/Ras/Raf/MEK/ERK signaling pathway. Moreover, HOXA3
      overexpressing and HOXA3-suppressing HT29 cells were subcutaneous injected into
      nod mice to confirm the regulation of HOXA3 on EGFR/Ras/Raf/MEK/ERK signaling in
      regulating tumor growth. HOXA3 was upregulated in colon tumor tissues and cell
      lines, and upregulated expression of HOXA3 was associated with low survival rate.
      Knockdown of HOXA3 suppressed cell viability and clone formation, while induced
      cell apoptosis. HOXA3 knockdown could not induce the increase of cell apoptosis
      on the condition of EGFR overexpression. In vivo xenograft studies, HOXA3
      suppressing cells showed less tumorigenic. Moreover, HOXA3 knockdown suppressed
      the activation of EGFR/Ras/Raf/MEK/ERK signaling pathway. To conclude, this study
      indicated that HOXA3 might act as a promoter of human colon cancer formation by
      regulating EGFR/Ras/Raf/MEK/ERK signaling pathway. HOXA3 might be a potential
      therapeutic target for the treatment of colon cancer.

PMID- 29073729
TI  - Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH
      positive breast cancer stem cells and the NF-kappaB signaling pathway.
AB  - Triple-negative breast tumors are very aggressive and contain relatively high
      proportion of cancer stem cells, and are resistant to chemotherapeutic drugs
      including cisplatin. To overcome these limitations, we combined eugenol, a
      natural polyphenolic molecule, with cisplatin to normalize cisplatin mediated
      toxicity and potential drug resistance. Interestingly, the combination treatment
      provided significantly greater cytotoxic and pro-apoptotic effects as compared to
      treatment with eugenol or cisplatin alone on several triple-negative breast
      cancer cells both in vitro and in vivo. Furthermore, adding eugenol to cisplatin
      potentiated the inhibition of breast cancer stem cells by inhibiting ALDH enzyme
      activity and ALDH-positive tumor initiating cells. We provide also clear evidence
      that eugenol potentiates cisplatin inhibition of the NF-kappaB signaling pathway.
      Indeed, the binding of NF-kappaB to its cognate binding sites present in the
      promoters of IL-6 and IL-8 was dramatically reduced, which led to potent down
      regulation of the IL-6 and IL-8 cytokines upon combination treatment relative to
      the single agents. Similar effects were observed on proliferation, inhibition of
      epithelial-to-mesenchymal transition and stemness markers in tumor xenografts.
      These results provide strong preclinical justification for combining cisplatin
      with eugenol as therapeutic approach for triple-negative breast cancers through
      targeting the resistant ALDH-positive cells and inhibiting the NF-kappaB pathway.

PMID- 29073730
TI  - Molecular and epidemiological analysis of pandemic and post-pandemic influenza
      A(H1N1)pdm09 virus from central India.
AB  - Influenza A(H1N1)pdm09 virus pandemic struck India in 2009 and continues to cause
      outbreaks in its post-pandemic phase. Diminutive information is available about
      influenza A(H1N1)pdm09 from central India. This observational study presents
      epidemiological and molecular findings for the period of 6 years. Throat swab
      samples referred from districts of Madhya Pradesh were subjected to diagnosis of
      influenza A(H1N1)pdm09 following WHO guidelines. Clinical and epidemiological
      data were recorded and analyzed. Hemagglutinin (HA) gene sequencing and
      phylogenetic analysis were performed. The H275Y mutation responsible for
      antiviral resistance was tested using allelic real-time RT-PCR. Out of 7365
      tested samples, 2406 (32.7%) were positive for influenza A(H1N1)pdm09, of which
      363 (15.08%) succumbed to infection. Significant trends were observed in
      positivity (chi2  = 50.8; P < 0.001) and mortality (chi2  = 24.4; P < 0.001) with
      increasing age. Mutations having clinical and epidemiological importance were
      detected. Phylogenetic analysis of HA gene sequences revealed that clade 7, 6A,
      and 6B viruses were in circulation. Oseltamivir resistance was detected in three
      fatal cases. Influenza A(H1N1)pdm09 viruses having genetic diversity were
      detected from central India and continues to be a concern for public health. This
      study highlights the need of year-round monitoring by establishment of strong
      molecular and clinical surveillance program.

PMID- 29073731
TI  - Performance evaluation of Cepheid Xpert Norovirus kit with a user-modified
      protocol.
AB  - The Cepheid Xpert(r) Norovirus kit automates sample processing, nucleic acid
      extraction, and real-time reverse transcription polymerase chain reactions (RT
      PCRs) to detect norovirus genogroups I (GI) and II (GII). Eighty-five stool
      samples collected between February 2015 and May 2017 were used to compare the
      performance of a user-modified Xpert assay against a clinically validated
      laboratory-developed test (LDT). Of the 85 samples, 54 were previously archived
      in -80 degrees C freezer. The remaining 31 were fresh samples tested concurrently
      with the LDT. The results of all samples tested using the Xpert kit and LDT were
      found to be concordant, including 12 GI- and 42 GII-positive samples, 1 GI and
      GII coinfection, and 30 negative samples. Comparison of the assays showed perfect
      concordance with a kappa coefficient score of 1.00 (95%CI from 1.00 to 1.00). Of
      the 30 negative stool samples tested, three samples were positive for rotavirus
      detected using an immunochromatographic assay, with no cross-reactivity shown in
      both LDT and Xpert assays. In-run sample processing control of the Xpert assay
      for all negative samples tested showed no/minor inhibition. Compared to the LDT,
      the Xpert assay produced similar or better Ct values for detection. It also
      showed better mitigation of PCR inhibition in stool sample testing.

PMID- 29073732
TI  - Hadamard editing of glutathione and macromolecule-suppressed GABA.
AB  - The primary inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the
      major antioxidant glutathione (GSH) are compounds of high importance for the
      function and integrity of the human brain. In this study, a method for
      simultaneous J-difference spectral-edited magnetic resonance spectroscopy (MRS)
      of GSH and GABA with suppression of macromolecular (MM) signals at 3 T is
      proposed. MM-suppressed Hadamard encoding and reconstruction of MEGA (Mescher
      Garwood)-edited spectroscopy (HERMES) consists of four sub-experiments (TE = 80
      ms), with 20-ms editing pulses applied at: (A) 4.56 and 1.9 ppm; (B) 4.56 and 1.5
      ppm; (C) 1.9 ppm; and (D) 1.5 ppm. One Hadamard combination (A + B - C - D)
      yields GSH-edited spectra, and another (A - B + C - D) yields GABA-edited
      spectra, with symmetric suppression of the co-edited MM signal. MM-suppressed
      HERMES, conventional HERMES and separate Mescher-Garwood point-resolved
      spectroscopy (MEGA-PRESS) data were successfully acquired from a (33 mm)3 voxel
      in the parietal lobe in 10 healthy subjects. GSH- and GABA-edited MM-suppressed
      HERMES spectra were in close agreement with the respective MEGA-PRESS spectra.
      Mean GABA (and GSH) estimates were 1.10 +/- 0.15 i.u. (0.59 +/- 0.12 i.u.) for MM
      suppressed HERMES, and 1.13 +/- 0.09 i.u. (0.66 +/- 0.09 i.u.) for MEGA-PRESS.
      Mean GABA (and GSH) differences between MM-suppressed HERMES and MEGA-PRESS were 
      0.03 +/- 0.11 i.u. (-0.07 +/- 0.11 i.u.). The mean signal-to-noise ratio (SNR)
      improvement of MM-suppressed HERMES over MEGA-PRESS was 1.45 +/- 0.25 for GABA
      and 1.32 +/- 0.24 for GSH. These results indicate that symmetric suppression of
      the MM signal can be accommodated into the Hadamard editing framework. Compared
      with sequential single-metabolite MEGA-PRESS experiments, MM-suppressed HERMES
      allows for simultaneous edited measurements of GSH and GABA without MM
      contamination in only half the scan time, and SNR is maintained.

PMID- 29073733
TI  - Tracing the breeding farm of domesticated pig using feature selection (Sus
      scrofa).
AB  - OBJECTIVE: Increasing food safety demands in the animal product market have
      created a need for a system to trace the food distribution process, from the
      manufacturer to the retailer, and genetic traceability is an effective method to
      trace the origin of animal products. In this study, we successfully achieved the
      farm tracing of 6,018 multi-breed pigs, using single nucleotide polymorphism
      (SNP) markers strictly selected through least absolute shrinkage and selection
      operator (LASSO) feature selection. METHODS: We performed farm tracing of
      domesticated pig (Sus scrofa) from SNP markers and selected the most relevant
      features for accurate prediction. Considering multi-breed composition of our
      data, we performed feature selection using LASSO penalization on 4,002 SNPs that
      are shared between breeds, which also includes 179 SNPs with small between-breed
      difference. The 100 highest-scored features were extracted from iterative
      simulations and then evaluated using machine-leaning based classifiers. RESULTS:
      We selected 1,341 SNPs from over 45,000 SNPs through iterative LASSO feature
      selection, to minimize between-breed differences. We subsequently selected 100
      highest-scored SNPs from iterative scoring, and observed high statistical
      measures in classification of breeding farms by cross-validation only using these
      SNPs. CONCLUSION: The study represents a successful application of LASSO feature
      selection on multi-breed pig SNP data to trace the farm information, which
      provides a valuable method and possibility for further researches on genetic
      traceability.

PMID- 29073734
TI  - Near-Field Three-Dimensional Planar Millimeter-Wave Holographic Imaging by Using
      Frequency Scaling Algorithm.
AB  - In this paper, a fast three-dimensional (3-D) frequency scaling algorithm (FSA)
      with large depth of focus is presented for near-field planar millimeter-wave
      (MMW) holographic imaging. Considering the cross-range range coupling term which
      is neglected in the conventional range migration algorithm (RMA), we propose an
      algorithm performing the range cell migration correction for de-chirped signals
      without interpolation by using a 3-D frequency scaling operation. First, to deal
      with the cross-range range coupling term, a 3-D frequency scaling operator is
      derived to eliminate the space variation of range cell migration. Then, a range
      migration correction factor is performed to compensate for the residual range
      cell migration. Finally, the imaging results are obtained by matched filtering in
      the cross-range direction. Compared with the conventional RMA, the proposed
      algorithm is comparable in accuracy but more efficient by using only chirp
      multiplications and fast Fourier transforms (FFTs). The algorithm has been tested
      with satisfying results by both simulation and experiment.

PMID- 29073735
TI  - Spatiotemporal Pixelization to Increase the Recognition Score of Characters for
      Retinal Prostheses.
AB  - Most of the retinal prostheses use a head-fixed camera and a video processing
      unit. Some studies proposed various image processing methods to improve visual
      perception for patients. However, previous studies only focused on using spatial
      information. The present study proposes a spatiotemporal pixelization method
      mimicking fixational eye movements to generate stimulation images for artificial
      retina arrays by combining spatial and temporal information. Input images were
      sampled with a resolution that was four times higher than the number of pixel
      arrays. We subsampled this image and generated four different phosphene images.
      We then evaluated the recognition scores of characters by sequentially presenting
      phosphene images with varying pixel array sizes (6 * 6, 8 * 8 and 10 * 10) and
      stimulus frame rates (10 Hz, 15 Hz, 20 Hz, 30 Hz, and 60 Hz). The proposed method
      showed the highest recognition score at a stimulus frame rate of approximately 20
      Hz. The method also significantly improved the recognition score for complex
      characters. This method provides a new way to increase practical resolution over
      restricted spatial resolution by merging the higher resolution image into high
      frame time slots.

PMID- 29073737
TI  - Association, Distribution, Liberation, and Rheological Balances of
      Alkyldimethylbenzylammonium Chlorides (C12-C16).
AB  - It is known that cationic surfactants have an antimicrobial effect and act as
      enhancers. This paper studies three cationic surfactants from the group of
      alkyldimethylbenzylammonium chlorides (dodecyl-, tetradecyl-, and hexadecyl).
      Interest is focused on the association of the surfactants with respect to
      temperature, partition balances and their influence on drug release, rheological
      properties, and the pH of hydrogels. The critical micelle concentrations (CMC) of
      the surfactants were estimated from dependencies of conductivity, density,
      spectrofluorimetry, and UV-VIS spectrophotometry on molarity in the temperature
      range of 25-50  degrees C. It was found that the temperature dependence of a CMC
      is U-shaped, with its minimum at 30  degrees C, and the CMC value decreases as
      the length of the chain increases. The pseudo-phase separation model was used for
      the calculation of various thermodynamic parameters, such as the Gibbs free
      energies (spontaneous process), enthalpies (exothermic process), and entropies of
      the micelles' formation, CMCs, and the degree of counterion binding. All
      thermodynamic parameters, as functions of the temperature, were estimated. It was
      found that partition coefficients increase as the length of the alkyl chain and
      the pH = (5.0-7.0) increase. The influences of surfactants, below and above the
      CMC, on drug (chlorhexidine dihydrochloride) release from hydrogels, rheological
      properties, and pH at 30  degrees C were studied. Also, the amounts of the
      released drug increase as the alkyl chains of the surfactants prolongate. The
      amounts of the released drug with the surfactant below the CMC are greater than
      that above the CMC. All hydrogels (regardless of the length of the alkyl chain)
      exhibit a non-Newtonian pseudo-plastic flow. The results obtained will be used in
      the formulation of the drug and surfactants into dosage forms.

PMID- 29073738
TI  - On the Hole Injection for III-Nitride Based Deep Ultraviolet Light-Emitting
      Diodes.
AB  - The hole injection is one of the bottlenecks that strongly hinder the quantum
      efficiency and the optical power for deep ultraviolet light-emitting diodes (DUV
      LEDs) with the emission wavelength smaller than 360 nm. The hole injection
      efficiency for DUV LEDs is co-affected by the p-type ohmic contact, the p-type
      hole injection layer, the p-type electron blocking layer and the multiple quantum
      wells. In this report, we review a large diversity of advances that are currently
      adopted to increase the hole injection efficiency for DUV LEDs. Moreover, by
      disclosing the underlying device physics, the design strategies that we can
      follow have also been suggested to improve the hole injection for DUV LEDs.

PMID- 29073736
TI  - In Situ Dark Adaptation Enhances the Efficiency of DNA Extraction from Mature Pin
      Oak (Quercus palustris) Leaves, Facilitating the Identification of Partial
      Sequences of the 18S rRNA and Isoprene Synthase (IspS) Genes.
AB  - Mature oak (Quercus spp.) leaves, although abundantly available during the
      plants' developmental cycle, are rarely exploited as viable sources of genomic
      DNA. These leaves are rich in metabolites difficult to remove during standard DNA
      purification, interfering with downstream molecular genetics applications. The
      current work assessed whether in situ dark adaptation, to deplete sugar reserves
      and inhibit secondary metabolite synthesis could compensate for the difficulties
      encountered when isolating DNA from mature leaves rich in secondary metabolites.
      We optimized a rapid, commercial kit based method to extract genomic DNA from
      dark- and light-adapted leaves. We demonstrated that in situ dark adaptation
      increases the yield and quality of genomic DNA obtained from mature oak leaves,
      yielding templates of sufficiently high quality for direct downstream
      applications, such as PCR amplification and gene identification. The quality of
      templates isolated from dark-adapted pin oak leaves particularly improved the
      amplification of larger fragments in our experiments. From DNA extracts prepared
      with our optimized method, we identified for the first time partial segments of
      the genes encoding 18S rRNA and isoprene synthase (IspS) from pin oak (Quercus
      palustris), whose full genome has not yet been sequenced.

PMID- 29073740
TI  - News From the Foundation for Physical Therapy.

PMID- 29073739
TI  - Association of Early Outpatient Rehabilitation With Health Service Utilization in
      Managing Medicare Beneficiaries With Nontraumatic Knee Pain: Retrospective Cohort
      Study.
AB  - Background: Nontraumatic knee pain (NTKP) is highly prevalent in adults 65 years
      of age and older. Evidence-based guidelines recommend early use of
      rehabilitation; however, there is limited information comparing differences in
      health care utilization when rehabilitation is included in the management of
      NTKP. Objectives: To describe the overall health care utilization associated with
      the management of NTKP; estimate the proportion of people who receive outpatient
      rehabilitation services; and evaluate the timing of outpatient rehabilitation and
      its association with other health care utilization. Design: Rretrospective cohort
      study was conducted using a random 10% sample of 2009-2010 Medicare claims. The
      sample included 52,504 beneficiaries presenting within the ambulatory setting for
      management of NTKP. Methods: Exposure to outpatient rehabilitative services
      following the NTKP index ambulatory visit was defined as 1) no rehabilitation; 2)
      early rehabilitation (1-15 days); 3) intermediate rehabilitation (16-120 days);
      and 4) late rehabilitation (>120 days). Logistic regression models were fit to
      analyze the association of rehabilitation timing with narcotic analgesic use,
      utilization of nonsurgical invasive procedure, and knee surgery during a 12-month
      follow-up period. Results: Only 11.1% of beneficiaries were exposed to outpatient
      rehabilitation services. The likelihood of using narcotics, nonsurgical invasive
      procedures, or surgery was significantly less (adjusted odds ratios; 0.67, 0.50,
      0.58, respectively) for those who received early rehabilitation when compared to
      no rehabilitation. The exposure-outcome relationships were reversed in the
      intermediate and late rehabilitation cohorts. Limitations: This was an
      observational study, and residual confounding could affect the observed
      relationships. Therefore, definitive conclusions regarding the causal effect of
      rehabilitation exposure and reduced utilization of more aggressive interventions
      cannot be determined at this time. Conclusions: Early referral for outpatient
      rehabilitation may reduce the utilization of health services that carry greater
      risks or costs in those with NTKP.

PMID- 29073741
TI  - A Systematic Review of the Effectiveness of Medical Cannabis for Psychiatric,
      Movement and Neurodegenerative Disorders.
AB  - The discovery of endocannabinoid's role within the central nervous system and its
      potential therapeutic benefits have brought forth rising interest in the use of
      cannabis for medical purposes. The present review aimed to synthesize and
      evaluate the available evidences on the efficacy of cannabis and its derivatives
      for psychiatric, neurodegenerative and movement disorders. A systematic search of
      randomized controlled trials of cannabis and its derivatives were conducted via
      databases (PubMed, Embase and the Cochrane Central Register of Controlled
      Trials). A total of 24 reports that evaluated the use of medical cannabis for
      Alzheimer's disease, anorexia nervosa, anxiety, dementia, dystonia, Huntington's
      disease, Parkinson's disease, post-traumatic stress disorder (PTSD), psychosis
      and Tourette syndrome were included in this review. Trial quality was assessed
      with the Cochrane risk of bias tool. There is a lack of evidence on the
      therapeutic effects of cannabinoids for amyotrophic lateral sclerosis and
      dystonia. Although trials with positive findings were identified for anorexia
      nervosa, anxiety, PTSD, psychotic symptoms, agitation in Alzheimer's disease and
      dementia, Huntington's disease, and Tourette syndrome, and dyskinesia in
      Parkinson's disease, definitive conclusion on its efficacy could not be drawn.
      Evaluation of these low-quality trials, as rated on the Cochrane risk of bias
      tools, was challenged by methodological issues such as inadequate description of
      allocation concealment, blinding and underpowered sample size. More adequately
      powered controlled trials that examine the long and short term efficacy, safety
      and tolerability of cannabis for medical use, and the mechanisms underpinning the
      therapeutic potential are warranted.

PMID- 29073742
TI  - Peripheral Signatures of Psychiatric Disorders: MicroRNAs.
AB  - MicroRNAs (miRNAs) are 22 nucleotide long RNA transcripts, their synthesis starts
      in nucleus and continues in cytoplasm. As being critical for post-transcriptional
      regulators of gene expression they have been investigated in psychiatric
      disorders. There are numerous studies performed in peripheral tissues for
      psychiatric disorders. Here in this article, we aimed to review some common
      miRNAs denoted significant in at least two studies and their relevance to
      psychiatric research. We focused on miR-320, miR-106, miR-34, miR-223, miR-107,
      and miR-134.

PMID- 29073743
TI  - Eye Movement Desensitization and Reprocessing to Facilitate Posttraumatic Growth:
      A Prospective Clinical Pilot Study on Ferry Disaster Survivors.
AB  - Objective: The purpose of this study was to investigate the therapeutic effects
      of eye movement desensitization and reprocessing (EMDR) on post-traumatic growth
      (PTG). Methods: This study was conducted using a sample of ten survivors of a
      large-scale maritime disaster that occurred in the Yellow Sea, South Korea, in
      April 2014. A total of eight EMDR sessions were administered by a psychiatrist at
      two-week intervals over a period of five months, starting two or three months
      after the accident. Post-Traumatic Growth Inventory (PTGI), Stress-Related Growth
      Scale (SRGS), Clinician-Administered PTSD Scale (CAPS), and Connor-Davidson
      Resilience Scale (CD-RISC) were measured before treatment, after sessions 4 and
      8, and at three months after treatment completion. Results: After three months
      from treatment completion, significant increases were observed in PTG (PTGI:
      Z(8)=-2.380, p=0.017; SRGS: Z(8)=-2.380, p=0.017) and resilience (CD-RISC: Z(8)=
      2.386, p=0.017). A decrease in post-traumatic stress disorder (PTSD) level was
      also significant (CAPS: Z(8)=-2.176, p=0.030). The reduction of CAPS scores was
      correlated with increases of PTGI (rho=0.78, p=0.023) and SRGS (rho=0.79,
      p=0.020) scores. The changes in CAPS, PTGI, and SRGS scores between time point of
      end 8-session and three months follow-up was not significant (all p>0.05).
      Subjects with higher pre-treatment CD-RISC scores showed more significant
      improvements in PTGI (rho=0.88, p=0.004) and SRGS (rho=0.83, p=0.010) scores
      after treatment than did those with lower pre-treatment CD-RISC scores.
      Conclusion: EMDR therapy using standard protocol for trauma processing helped
      facilitating PTG in disaster survivors. To generalize these findings, further
      controlled studies comparing with other treatment modalities for PTSD are needed.

PMID- 29073744
TI  - A Retrospective Study of Long Acting Risperidone Use to Support Treatment
      Adherence in Youth with Conduct Disorder.
AB  - Objective: Risperidone has been widely used to control aggression and conduct
      disorder (CD) in youth; however, treatment compliance is a major problem in CD.
      Our aim is to evaluate the effectiveness and tolerability of long-acting
      risperidone (LAR) in treating nonadherent cases. Methods: The medical records of
      children and adolescents who had CD and were nonadherent to conventional drugs
      and psychosocial interventions (and therefore taking LAR) were reviewed. Informed
      consent on offlabel use of LAR was obtained from the parents. Clinical Global
      Impression (CGI) Severity (CGI-S) and CGI-Improvement scales were used and
      baseline and end points were compared. Results: The study comprised 14 children
      and adolescents (5 girls, 9 boys). All had comorbid disorders: substance use
      disorder (n=8), attention deficit hyperactivity disorder (n=6), and major
      depression (n=2). Mean duration of LAR use was 3.1 months (1.5-8 months). We
      observed significant improvements in the baseline and endpoint CGI-S scores for
      CD in all but one patient (Z=-3.198; p<0.001). Only mild adverse effects were
      observed: weight gain (n=2), sedation (n=1), leg cramps (n=1), and increased
      appetite with no weight gain (n=1). Conclusion: LAR is effective and tolerable
      for patients with CD who can't be medicated with oral preparations due to
      nonadherence to treatment. Even short-term LAR use is effective to get
      compliance. As CD predicts numerous problems in adulthood, appropriate treatment
      is crucial. To our knowledge, this is the first study on LAR use in youth with
      CD. The use of LAR deserves careful consideration and further controlled studies
      are needed to confirm our findings.

PMID- 29073745
TI  - Increased Serum G Protein-coupled Estrogen Receptor 1 Levels and Its Diagnostic
      Value in Drug Naive Patients with Major Depressive Disorder.
AB  - Objective: The facts that depression is more prevalent in females than in males
      and females are exposed to depression more commonly during certain hormonal
      fluctuating periods indicate the role of sex hormones in physiopathology.
      Estrogen acts over estrogen receptors alpha and beta and recently identified G
      protein-coupled estrogen receptor 1 (GPER1). The present study aimed, for the
      first time, to evaluate serum GPER1 levels in drug-naive major depressive
      disorder (MDD) patients. Methods: The study included 56 newly diagnosed drug
      naive MDD patients aged between 18 and 50 years and 42 age- and gender-matched
      healthy volunteers. Medical history was obtained and physical examinations,
      laboratory tests, and the Hamilton Depression Rating Scale (HAM-D), Hamilton
      Anxiety Rating Scale (HAM-A) were performed. The serum GPER1 levels were
      measured. Results: The HAM-D score was significantly higher in the MDD patients
      than in the controls. The GPER1 level was significantly higher in the MDD
      patients than in the controls. A positive correlation was found with GPER1 levels
      and depression scores. The receiver operating characteristic analysis revealed
      sensitivity, specificity, positive predictive value, and negative predictive
      value as 82.1%, 90.5%, 92.0%, and 79.2%, respectively, for the presence of
      depression, when the serum GPER1 value was >=0.16. Conclusion: This study
      demonstrated significantly higher serum GPER1 levels in the MDD patients than in
      the controls, a positive correlation was found between GPER1 levels and
      depression scores and serum GPER1 level was valuable in predicting the presence
      of depression.

PMID- 29073746
TI  - Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in
      Borderline Personality Disorder.
AB  - Objective: Impulsivity is a core feature of borderline personality disorder (BPD)
      and antisocial personality disorder (ASPD) that likely arises from combined
      genetic and environmental influences. The interaction of the low activity variant
      of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been
      shown to predict aggression in clinical and non-clinical populations. Although
      impulsivity is a risk factor for aggression in BPD and ASPD, little research has
      investigated potential gene-environment (G*E) influences impacting its expression
      in these conditions. Moreover, G*E interactions may differ by diagnosis. Methods:
      Full factorial analysis of variance was employed to investigate the influence of
      monoamine oxidase-A (MAO-A) genotype, childhood abuse, and diagnosis on Barratt
      Impulsiveness Scale-11 (BIS-11) scores in 61 individuals: 20 subjects with BPD,
      18 subjects with ASPD, and 23 healthy controls. Results: A group*genotype*abuse
      interaction was present (F(2,49)=4.4, p=0.018), such that the interaction of MAOA
      L and childhood abuse predicted greater BIS-11 motor impulsiveness in BPD.
      Additionally, BPD subjects reported higher BIS-11 attentional impulsiveness
      versus ASPD participants (t(1,36)=2.3, p=0.025). Conclusion: These preliminary
      results suggest that MAOA-L may modulate the impact of childhood abuse on
      impulsivity in BPD. Results additionally indicate that impulsiveness may be
      expressed differently in BPD and ASPD.

PMID- 29073747
TI  - Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with
      Mood Disorders.
AB  - Objective: The aim of this study was to examine the validity of the Korean
      version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood
      disorder patients. Methods: A total of 454 patients who diagnosed as mood
      disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders,
      clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and
      major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32
      R2 (KHCL-32-R2). Results: The KHCL-32-R2 showed a three-factorial structure
      (eigenvalue >2) that accounted for 43.26% of the total variance. Factor 1 was
      labeled "active/elated" and included 16 items; factor 2, "irritable/distractible"
      and included 9 items; and factor 3 was labeled "risk-taking/indulging" and
      included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score
      distinguished between BD and MDD, which yielded a sensitivity of 70% and a
      specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15
      with maximized sensitivity (0.67) and specificity (0.66). Cronbach's alpha of
      KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79,
      respectively. Correlations between KHCL-32-R2 and Montgomery- Asberg Depression
      Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder
      Questionnaire were -0.66 (p=0.41), -0.14 (p=0.9), and 0.61 (p<0.001),
      respectively. Conclusion: The KHCL-32-R2 may be a useful tool in distinguishing
      between bipolar and depressive patients in clinical settings.

PMID- 29073748
TI  - Comparing the Effects of Bupropion and Escitalopram on Excessive Internet Game
      Play in Patients with Major Depressive Disorder.
AB  - Objective: Several studies have suggested the efficacy of bupropion and
      escitalopram on reducing the excessive internet game play. We hypothesized that
      both bupropion and escitalopram would be effective on reducing the severity of
      depressive symptoms and internet gaming disorder (IGD) symptoms in patients with
      both major depressive disorder and IGD. However, the changes in brain
      connectivity between the default mode network (DMN) and the salience network were
      different between bupropion and escitalopram due to their different
      pharmacodynamics. Methods: This study was designed as a 12-week double blind
      prospective trial. Thirty patients were recruited for this research (15 bupropion
      group+15 escitalopram group). To assess the differential functional connectivity
      (FC) between the hubs of the DMN and the salience network, we selected 12 regions
      from the automated anatomical labeling in PickAtals software. Results: After drug
      treatment, the depressive symptoms and IGD symptoms in both groups were improved.
      Impulsivity and attentional symptoms in the bupropion group were significantly
      decreased, compared to the escitalopram group. After treatment, FC within only
      the DMN in escitalopram decreased while FC between DMN and salience network in
      bupropion group decreased. Bupropion was associated with significantly decreased
      FC within the salience network and between the salience network and the DMN,
      compared to escitalopram. Conclusion: Bupropion showed greater effects than
      escitalopram on reducing impulsivity and attentional symptoms. Decreased brain
      connectivity between the salience network and the DMN appears to be associated
      with improved excessive IGD symptoms and impulsivity in MDD patients with IGD.

PMID- 29073749
TI  - Neurodevelopmental Changes in Social Reinforcement Processing: A Functional
      Magnetic Resonance Imaging Study.
AB  - Objective: In the current study we investigated neurodevelopmental changes in
      response to social and non-social reinforcement. Methods: Fifty-three healthy
      participants including 16 early adolescents (age, 10-15 years), 16 late
      adolescents (age, 15-18 years), and 21 young adults (age, 21-25 years) completed
      a social/non-social reward learning task while undergoing functional magnetic
      resonance imaging. Participants responded to fractal image stimuli and received
      social or non-social reward/non-rewards according to their accuracy. ANOVAs were
      conducted on both the blood oxygen level dependent response data and the product
      of a context-dependent psychophysiological interaction (gPPI) analysis involving
      ventromedial prefrontal cortex (vmPFC) and bilateral insula cortices as seed
      regions. Results: Early adolescents showed significantly increased activation in
      the amygdala and anterior insula cortex in response to non-social monetary
      rewards relative to both social reward/non-reward and monetary non-rewards
      compared to late adolescents and young adults. In addition, early adolescents
      showed significantly more positive connectivity between the vmPFC/bilateral
      insula cortices seeds and other regions implicated in reinforcement processing
      (the amygdala, posterior cingulate cortex, insula cortex, and lentiform nucleus)
      in response to non-reward and especially social non-reward, compared to late
      adolescents and young adults. Conclusion: It appears that early adolescence may
      be marked by: (i) a selective increase in responsiveness to non-social, relative
      to social, rewards; and (ii) enhanced, integrated functioning of reinforcement
      circuitry for non-reward, and in particular, with respect to posterior cingulate
      and insula cortices, for social non-reward.

PMID- 29073750
TI  - Early Improvement and Marriage Are Determinants of the 12-Month Treatment Outcome
      of Paroxetine in Outpatients with Panic Disorder.
AB  - Objective: In this study, we investigated the determinants of remission and
      discontinuation of paroxetine pharmacotherapy in outpatients with panic disorder
      (PD). Methods: Subjects were 79 outpatients diagnosed with PD who took 10-40
      mg/day of paroxetine for 12 months. The candidate therapeutic determinants
      included the serotonin transporter gene-linked polymorphic region and the 
      1019C/G promoter polymorphism of the serotonin receptor 1A as genetic factors,
      educational background and marital status as environmental factors, and early
      improvement (EI) at 2 weeks as a clinical factor were assessed. The Clinical
      Global Impression scale was used to assess the therapeutic effects of the
      pharmacotherapy. Results: Cox proportional hazards regression was performed to
      investigate the significant predictive factors of remission and discontinuation.
      EI was only a significant predictive factor of remission. EI was a significant
      predictive factor of remission (hazard ratio [HR], 2.709; 95% confidence interval
      [CI], 1.177-6.235). Otherwise, EI and marital status were significant predictive
      factors of the discontinuation. EI (HR, 0.266; 95% CI, 0.115-0.617) and being
      married (HR, 0.437; 95% CI, 0.204-0.939) were considered to reduce the risk of
      treatment discontinuation. In married subjects, EI was a significant predictive
      factor of the discontinuation (HR, 0.160; 95% CI, 0.045-0.565). However, in
      unmarried subjects, EI was not a significantly predictive factor for the
      discontinuation. Conclusion: EI achievement appears to be a determinant of PD
      remission in paroxetine treatment. In married PD patients, EI achievement also
      appears to reduce a risk of discontinuation of paroxetine treatment.

PMID- 29073751
TI  - Paroxetine versus Venlafaxine and Escitalopram in Korean Patients with Major
      Depressive Disorder: A Randomized, Rater-blinded, Six-week Study.
AB  - Objective: The purpose of this study was to compare the efficacy and safety of
      escitalopram, paroxetine and venlafaxine in Korean patients with major depressive
      disorder (MDD). Methods: A total of 449 Korean MDD patients were recruited in a
      six-week, randomized, rater-blinded, active-controlled trial and were evenly
      randomized to paroxetine, venlafaxine, or escitalopram treatment. Results: When
      comparing the mean difference for the Montgomery-Asberg Depression Rating Scale
      (MADRS) and the Hamilton Depression Rating Scale (HDRS) total scores during six
      weeks, paroxetine (-6.4+/-0.4, and -5.4+/-0.4, respectively) was found to be
      significantly superior to escitalopram (-3.7+/-0.5 and -3.1+/-0.4, respectively).
      Venlafaxine had a significantly lower MADRS total score (-5.4+/-0.4) than
      escitalopram. When adjusting baseline variables, the response, according to the
      MADRS and HDRS scores, in the paroxetine group was greater than that for the
      escitalopram group (odds ratio [OR]=2.43, 95% confidence interval [CI]=1.42-4.16
      for MADRS; and OR=2.32, 95% CI=1.35-3.97 for HDRS) and the venlafaxine group
      (OR=1.94, 95% CI=1.17-3.21 for MADRS; and OR=1.71, 95% CI=1.03-2.83 for HDRS).
      Despite that the overall tolerability was high and similar among the three
      groups, a total of 268 subjects (59.7%) prematurely discontinued treatment,
      representing the main limitation of the present study. Conclusion: Although a low
      study completion rate limits generalizability, our findings suggest that
      paroxetine might be superior to escitalopram in Korean MDD patients. Further
      studies should be conducted to draw a definite conclusion.

PMID- 29073752
TI  - RORA Polymorphism Interacts with Childhood Maltreatment in Determining Anxiety
      Sensitivity by Sex: A Preliminary Study in Healthy Young Adults.
AB  - Objective: Recent studies have reported associations of retinoid-related orphan
      receptor alpha (RORA) gene single nucleotide polymorphisms (SNPs) with depression
      and anxiety disorders. Based on these, we attempt to test whether RORA
      polymorphism is associated with anxiety sensitivity (AS), the intermediate
      phenotype of depression and anxiety disorders. Considering gene-environment
      interactions and sex differences in AS, childhood maltreatment (CM) and sex were
      considered as confounders. Methods: Two-hundred and five healthy young Korean
      adults (female: 98, male: 107; age, 23.0+/-3.2 years) completed genotyping for
      the RORA SNP rs11071547, as well as measures for AS and CM. Generalized linear
      models were used to examine the main and interaction effects of RORA genotype,
      CM, and sex in determining AS. Results: The main effect of RORA polymorphisms was
      not found (p=0.760) whereas the main effect of CM and interaction effects among
      sex, genotype, and maltreatment were significant on AS. In separate analyses by
      sex, the interaction effect between RORA genotype and maltreatment was
      significant only in males (p<0.001). In females, the main effects of genotype and
      CM were significant (both were p<0.001), in which both a history of CM and C
      genotype tended to be associated with higher AS. Conclusion: The association
      between RORA polymorphism and AS might differ by sex. The interaction between
      RORA polymorphism and CM was significant only in males whereas RORA genotype and
      CM independently associated with AS in females. Further studies are encouraged to
      confirm the relationship between RORA polymorphism and AS.

PMID- 29073753
TI  - Lithium Intoxication: A Possible Interaction with Moxifloxacin.
AB  - Lithium is a well-known treatment for patients with mood disorders. Intoxication
      by lithium may be lethal particularly in elderly due to altered pharmacokinetics,
      renal impairment or multiple drug use. We presented a 74-year-old female patient
      who had been stabile with lithium carbonate 600 mg/day for 5 years and developed
      lithium intoxication after bronchiolitis. She presented with altered mental
      status. The neurological signs resolved slowly after lithium and moxifloxacin
      were stopped immediately and fluid resuscitation administered. Considering
      possible drug interactions on elderly patients receiving lithium is essential.

PMID- 29073754
TI  - Hiccup Due to Aripiprazole Plus Methylphenidate Treatment in an Adolescent with
      Attention Deficit and Hyperactivity Disorder and Conduct Disorder: A Case Report.
AB  - Our case had hiccups arising in an adolescent with the attention deficit and
      hyperactivity disorder (ADHD) and conduct disorder (CD) after adding aripiprazole
      treatment to extended-release methylphenidate. Actually, antipsychotics are also
      used in the treatment of hiccups, but studies suggest that they can cause hiccups
      as well. Within 12 hours of taking 2.5 mg aripiprazole added to extended-release
      methylphenidate at a dose of 54 mg/day, 16-year-old boy began having hiccups in
      the morning, which lasted after 3-4 hours. As a result, aripiprazole was
      discontinued and methylphenidate was continued alone because we could not
      convince the patient to use another additional drug due to this side effect.
      Subsequently, when his behavior got worsened day by day, his mother administered
      aripiprazole alone again at the dose of 2.5 mg/day at the weekend and continued
      treatment because hiccup did not occur again. But when it was administered with
      methylphenidate on Monday, hiccup started again next morning and lasted one hour
      at this time. In conclusion, we concluded that concurrent use of methylphenidate
      and aripiprazole in this adolescent led to hiccups.

PMID- 29073755
TI  - Neutropenia with Multiple Antipsychotics Including Dose Dependent Neutropenia
      with Lurasidone.
AB  - Antipsychotic-induced agranulocytosis is a significant side effect that is known
      to occur with most of the antipsychotic medications. It usually resolves once the
      medications are stopped and patients are able to be switched over to another
      antipsychotic medication. Lurasidone has not been reported to cause leukopenia
      and neutropenia. This case report is of a patient with a past history of
      risperidone induced-aganulocytosis developing dose related leukopenia and
      neutropenia with lurasidone.

PMID- 29073756
TI  - High Dose Ofloxacin-induced Bimodal Hallucinations in a 4 Years Old Child.
AB  - Ofloxacin is a commonly used quinolone antibiotic both in adults as well as
      children. It is generally safe and well tolerated. Rarely, neurological and
      psychiatric adverse reactions are reported to occur with ofloxacin. We report a
      case of a child who developed delirium after ofloxacin treatment, that resolved
      after medication discontinuation and treatment with low dose olanzapine.

PMID- 29073757
TI  - Urticaria and Angioedema Associated with Fluoxetine.

PMID- 29073758
TI  - The Use of Fine-Needle Aspiration (FNA) Cytology in Patients with Thyroid Nodules
      in Asia: A Brief Overview of Studies from the Working Group of Asian Thyroid FNA
      Cytology.
AB  - Ultrasound-guided fine-needle aspiration (FNA) cytology is the most widely used
      screening and diagnostic method for thyroid nodules. Although Western guidelines
      for managing thyroid nodules and the Bethesda System for Reporting Thyroid
      Cytopathology are widely available throughout Asia, the clinical practices in
      Asia vary from those of Western countries. Accordingly, the Working Group of
      Asian Thyroid FNA Cytology encouraged group members to publish their works
      jointly with the same topic. The articles in this special issue focused on the
      history of thyroid FNA, FNA performers and interpreters, training programs of
      cytopathologists and cytotechnicians, staining methods, the reporting system of
      thyroid FNA, quality assurance programs, ancillary testing, and literature review
      of their own country's products. Herein, we provide a brief overview of thyroid
      FNA practices in China, India, Japan, Korea, the Philippines, Taiwan, and
      Thailand.

PMID- 29073759
TI  - Bioluminescent Probe for Tumor Hypoxia Detection via CYP450 Reductase in Living
      Animals.
AB  - Hypoxia is a pathogenic characteristic of solid tumors owing to absent or
      abnormal vasculature in the tumor microenvironment and essential in tumor
      progression, angiogenesis, metastasis, invasion and resistance to immune system
      and therapy. In hypoxic environments, CYP450 enzymes are more efficient than in
      normoxia. Herein, based on the reductive capacity of CYP450 enzymes/NADPH system,
      we managed to cage aminoluciferin developing a reaction-based bioluminescent
      probe as well as an imaging method for the hypoxia detection. Exhibiting enhanced
      about 3-fold total flux in big (1.2 cm-diameter) tumors, Hypoxia BioLuminescent
      probe (HBL) can afford potential utility for in cellulo and in vivo hypoxia
      imaging in tumor model mice.

PMID- 29073760
TI  - Catalytic Nitrogen-to-Ammonia Conversion by Osmium and Ruthenium Complexes.
AB  - Despite the critical role Ru and Os complexes have played in the development of
      transition metal dinitrogen chemistry, they have not been shown to mediate
      catalytic N2-to-NH3 conversion (N2RR), nor have M-NxHy complexes been derived
      from protonation of their M-N2 precursors. To help delineate factors for N2RR
      catalysis, we report on isostructural tris(phosphino)silyl Ru and Os complexes
      that mediate catalytic N2RR, and compare their activities with an isostructural
      Fe complex. The Os system is most active, and liberates more than 120 equiv NH3
      per Os center in a single batch experiment using Cp*2Co and [H2NPh2][OTf] as
      reductant and acid source. Isostructural Ru and Fe complexes generate little NH3
      under the same conditions. Protonation of Os-N2- affords a structurally
      characterized Os=NNH2+ hydrazido species that mediates NH3 generation, suggesting
      it is a plausible intermediate of the catalysis. Inactive Os hydrides are
      characterized that form during catalysis.

PMID- 29073762
TI  - Can Biomimetic Zinc Compounds Assist a (3 + 2) Cycloaddition Reaction? A
      Theoretical Perspective.
AB  - Compounds bearing tetrazole rings are valuable facets in numerous branches of
      chemistry including metabolic imaging and the production of drugs and high-energy
      materials. Synthesis of tetrazoles with the help of organocatalysts has
      intensively been explored, while enzyme-directed click chemistry has attracted
      less attention and was only used in inhibitor design so far. Herein, we have
      investigated the possibility of a biomimetic catalyst based on a Lewis acid
      approach by exploring the anionic cycloaddition of azide and acetonitrile
      catalyzed by ZnBr2 in comparison with different biomimetic Zn(II) models. Density
      functional based calculations in the gas phase and with implicit solvation
      indicate that a variety of bioinspired zinc complexes should be able to catalyze
      tetrazole formation with catalytic enhancements comparable to zinc bromide salts.
      Such bioinspired routes could provide new possibilities for the stereo- and
      regioselectively controlled synthesis of tetrazoles.

PMID- 29073763
TI  - Cation-pi Interaction Triggered-Fluorescence of Clay Fillers in Polymer
      Composites for Quantification of Three-Dimensional Macrodispersion.
AB  - It is a considerable challenge to realize 3D fluorescence quantification of
      macrodispersion of clay fillers in a polymer matrix mainly owing to quenching of
      light emission in the solid state. Herein, a strong light emission is generated
      within the interlaminated clay as a result of a cation-pi interaction between
      cationic surfactant and fluorescent polycyclic aromatic hydrocarbon when they are
      cointercalated into clay. Confocal laser scanning microscopy (CLSM) is applied
      for 3D imaging of macrodispersion of the fluorescence-labeled clay fillers in a
      silicone rubber matrix. More importantly, the quantification of macrodispersion
      of clay fillers in the overall polymer composite is established by a statistical
      model. The proposed method fills in an important gap in the standard for
      macrodispersion quantification of inorganic fillers in polymer composites.

PMID- 29073764
TI  - Retraction of "An Expeditious Route to Both Enantiomers of All Carbon Quaternary
      Stereocenters at C-3 Carbon of Lactams via [3,3]-Sigmatropic Rearrangement: Total
      Synthesis of (-)-Physostigmine".

PMID- 29073761
TI  - Targeted Gene Repression Using Novel Bifunctional Molecules to Harness Endogenous
      Histone Deacetylation Activity.
AB  - Epigenome editing is a powerful method for life science research and could give
      rise to new therapies for diseases initiated or maintained by epigenetic
      dysregulation, including several types of cancers and autoimmune disorders. In
      addition, much is still unknown about the mechanisms by which histone-modifying
      proteins work in concert to properly regulate gene expression. To investigate and
      manipulate complex epigenetic interactions in live cells, we have developed a
      small molecule platform for specifically inducing gene repression and histone
      deacetylation at a reporter gene. We synthesized bifunctional ligands, or
      chemical epigenetic modifiers (CEMs), that contain two functional groups: a FK506
      derivative capable of binding to a FKBP-Gal4 fusion transcription factor, and a
      histone deacetylase (HDAC) inhibitor that recruits HDAC-containing corepressor
      complexes. In our reporter cell line, which contains a GFP reporter allele
      upstream of a Gal4 DNA binding array in the murine Oct4 locus, our lead CEM
      repressed GFP expression by 50%. We also show that CEM recruitment of
      deacetylation activity causes marked deacetylation along our target loci. This
      system allowed us to detail the direct results of deacetylation to chromatin and
      measure the resulting gene expression in a chemically dependent and reversible
      manner. The CEMs system provides new insights into epigenetic gene regulation and
      has the potential to control disease-relevant gene regulation. The CEMs are
      derived from FDA-approved epigenetic modulator drugs, and use their pharmacology
      in a gene-specific way that avoids the toxicities and off-target effects caused
      by whole-cell application of these drugs.

PMID- 29073765
TI  - Should There Be Minimum Information Reporting Standards for Sensors?

PMID- 29073767
TI  - Arterial Stiffness Is Associated With QTc Interval Prolongation in Patients With
      Heart Failure.
AB  - BACKGROUND: A prolonged corrected QT (QTc) interval is a known risk factor for
      adverse cardiac events. Understanding the determinants and physiologic correlates
      of QTc is necessary for selecting proper strategies to reduce the risk of adverse
      events in high-risk patients. We sought to evaluate the role of arterial
      stiffness in heart failure as a determinant of QTc prolongation. METHOD: This was
      an observational study that recruited ambulatory heart failure patients (New York
      Heart Association Classes I-II) from an outpatient heart failure clinic. In the
      supine resting position, consented patients underwent noninvasive 12-lead
      electrocardiograph (ECG) and hemodynamic monitoring using BioZ Dx impedance
      cardiography. ECGs were evaluated by a reviewer blinded to clinical data, and QTc
      interval was automatically computed. Patients with pacing or bundle branch block
      (BBB) were analyzed separately. Strengths of associations were evaluated using
      Pearson's r coefficients and multivariate linear regression. RESULTS: The final
      sample ( N = 44) was 62 +/- 13 years of age and 64% male with ejection fraction
      of 34% +/- 12%. At univariate level, QTc interval moderately ( r > .50)
      correlated with cardiac output, left cardiac work index, systemic vascular
      resistance, and total arterial compliance in patients with intrinsically narrow
      QRS complexes. At the multivariate level, increasing systemic vascular resistance
      and decreasing total arterial compliance remained independent predictors of
      widening QTc interval in this group ( R2 = .54). No significant correlations were
      seen in patients with pacing or BBB. CONCLUSIONS: In the absence of conduction
      abnormalities, magnitude of arterial stiffness, an indirect measure of
      endothelial dysfunction, is associated with QTc interval prolongation.

PMID- 29073768
TI  - Educating Parents About Infant Language Development: A Randomized Controlled
      Trial.
AB  - A total of 427 women (aged 18-45 years) who delivered a singleton neonate without
      serious medical complications were randomized to watch either an educational
      intervention (n = 225) or the sudden infant death syndrome (n = 202) video.
      Linear mixed models showed that the intervention women significantly gained
      knowledge over time. Knowledge gain was largest among high-socioeconomic status
      (high-SES) and middle-SES English-speaking, smaller among low-SES Spanish
      speaking, and nonsignificant among low-SES English-speaking women. Analysis of
      deviance revealed that the intervention women of all SES learned strategies
      fostering secure attachment and language acquisition. Participants considered
      watching an educational video alongside the universal newborn hearing screening
      (UNHS) conveniently timed. The intervention women were more likely than the
      control women to recognize the importance of timely UNHS follow-up.

PMID- 29073769
TI  - Retrospective Cost Analysis of a Single-Center Reusable Flexible Ureterorenoscopy
      Program: A Comparative Cost Simulation of Disposable fURS as an Alternative.
AB  - OBJECTIVE: The increasing number of flexible ureterorenoscopy (fURS) procedures,
      the fragility of devices, and their growing maintenance and repair costs
      represent a substantial burden for urologic departments. Disposable single-use
      fURS devices offer many advantages over reusable fURS. Among them, the LithoVueTM
      model shows the best clinical utility. In our study, we assessed the economic
      aspects of reusable fURS application compared with the potential costs and
      benefits of single-use fURS (LithoVueTM). Indications for single-use fURS were
      proposed based on potential risk factors of reusable fURS damage. MATERIALS AND
      METHODS: This single-center retrospective analysis compared the actual cost of
      reusable fURS procedures with the potential costs of LithoVueTM based on the
      price offered by the manufacturer. Consecutive case analysis of damaged fURS was
      performed to determine potential risk factors associated with fURS damage.
      RESULTS: The study group consisted of 423 reusable fURS procedures conducted
      between January 2013 and December 2016. During this period, 102 (24.11%)
      diagnostic fURS and 321 (75.89%) fURS for kidney stone therapy were performed. In
      32 of 423 (7.57%) fURS cases, devices were postoperatively deemed defective, 9 of
      which were used for diagnostic procedures (9/102; 8.82%), 7 for stone removal
      (7/148; 4.73%), and 16 for stone removal and laser (Ho:YAG) application (16/173;
      9.25%). The average cost per reusable fURS procedure was found to be ?503.26.
      CONCLUSIONS: Disposable fURS is a more expensive option for high-volume centers.
      Based on our case analysis, laser disintegration treatment of multiple, large
      stones in the lower kidney pole of recurrent stone formers, as well as a steep
      infundibulopelvic angle (IPA <=50 degrees ), seems to be the main risk factor for
      fURS damage. For these cases, disposable fURS may be a cost-effective
      alternative; however, a prospective comparison of economic outcomes between
      disposable and reusable fURS, together with confirmation of the proposed damage
      risk factors, is needed.

PMID- 29073770
TI  - Contrafreeloading in Rats Is Adaptive and Flexible: Support for an Animal Model
      of Compulsive Checking.
AB  - Contrafreeloading involves working unnecessarily to obtain a reward that is
      otherwise freely available. It has been observed in numerous species and can be
      adaptive when it provides an organism with updated information about available
      resources. Humans frequently update their knowledge of the environment through
      checking behaviors. Compulsive checking occurs when such actions are performed
      with excessive frequency. In a putative animal model of compulsive checking, rats
      treated chronically with the dopamine agonist quinpirole display exaggerated
      contrafreeloading for water. Although this effect has been attributed to
      behavioral rigidity, some evidence suggests the behavior remains somewhat
      flexible and may be adaptive under certain conditions. We assessed the ability of
      quinpirole-treated rats with contrafreeloading experience to adapt to changing
      contingencies by requiring them to alternate between response levers. Rats
      treated with quinpirole or saline were first trained to obtain water by pressing
      either of two levers. Next, free water was made available for 8 days, and
      contrafreeloading was measured. Rates of contrafreeloading were significantly
      higher in the drug-treated rats than in controls. On the following 5 days, each
      reward caused the associated lever to become inactive until a reward was earned
      from the alternate lever. Quinpirole-treated rats learned this new response
      requirement more quickly than controls. Thus, exaggerated checking behavior
      induced by chronic quinpirole treatment can be advantageous when environmental
      contingencies change. These results provide support for this animal model of
      compulsive checking and hint at the presence of a specialized neural checking
      module involving the dopamine system.

PMID- 29073771
TI  - Are Measures of Character and Personality Distinct? Evidence From Observed-Score
      and True-Score Analyses.
AB  - Two studies were conducted to investigate redundancy between the character
      strengths found in the VIA model of character and familiar personality facets.
      Study 1 used a community sample ( N = 606) that completed a measure of character
      strengths, four personality inventories, and 17 criterion measures. The second
      study used Mechanical Turk workers ( N = 498) who completed measures of the
      HEXACO and VIA models and 111 criterion variables. Analyses were conducted using
      both observed scores and true score estimates, evaluating both predictive and
      conceptual overlap. Eight of 24 VIA scales proved to be largely redundant with
      one HEXACO personality facet, but only one VIA scale (Appreciation of Beauty) was
      largely redundant with Five Factor facets. All strength scales except
      Spirituality overlapped substantially with at least one personality facet. The
      results suggest the VIA Classification variables are strongly related to commonly
      measured personality facets, but the two models are not redundant.

PMID- 29073773
TI  - The prevalence, course and clinical correlates of migraine in Parkinson's
      disease: A multicentre case-controlled study.
AB  - Background Previous studies have reported a lower migraine prevalence in
      Parkinson's disease (PD) patients and improvements in migraine headaches after PD
      onset, but the clinical association of migraines with PD is unclear. Methods We
      analysed headache and migraine prevalence and clinical correlates in 436 PD
      patients (mean age, 69.3 +/- 7.8 years) and 401 age- and sex-matched controls
      (mean age, 69.2 +/- 8.6 years) in a case-controlled, multicentre study. Migraines
      were diagnosed by a questionnaire developed according to the International
      Classification of Headache Disorders, second edition. We evaluated changes in
      headache intensity, frequency and severity over several years around the onset of
      PD among PD patients with headaches or migraines, and over the past several years
      among control subjects with headaches or migraines. Results PD patients had lower
      lifetime (9.6% vs. 18.0%) and 1-year (6.7% vs. 11.0%) migraine prevalences than
      controls. However, lifetime (38.5% vs. 38.9%) and 1-year (26.1% vs. 26.2%)
      headache prevalence did not differ between PD patients and controls. After
      adjusting for gender, timing of the evaluation of headache changes, and recall
      period, PD patients with headaches or migraines exhibited a pronounced reduction
      in the intensity, frequency and overall severity of their headaches and migraines
      after the onset of PD compared with controls with headaches or migraines. PD
      patients with migraines exhibited a higher rate of depression and higher
      Pittsburgh Sleep Quality Index and PD sleep scale-2 scores than those without
      headaches. Conclusion While overall headache and migraine severity reduced after
      PD onset, the presence of migraines was associated with sleep disturbances and
      depression in PD patients.

PMID- 29073772
TI  - Radiographic Results of Nitinol Compression Staples for Hindfoot and Midfoot
      Arthrodeses.
AB  - BACKGROUND: The purpose of this study was to determine the radiographic union
      rate after midfoot and hindfoot arthrodeses using a new generation of nitinol
      staples, and to compare outcomes between a nitinol staple construct and a nitinol
      staple and threaded compression screw construct. METHODS: A retrospective chart
      review was performed to identify patients who underwent hindfoot or midfoot
      arthrodesis using a new generation of nitinol compression staples with or without
      a partially threaded cannulated screw with minimum 3-month radiographic follow
      up. The primary outcome variable was radiographic evidence of arthrodesis on
      radiographs and, when available, computed tomographic scan in patients who
      underwent midfoot or hindfoot arthrodesis using nitinol staples. Ninety-six
      patients and 149 joints were eligible for analysis. Median radiographic follow-up
      was 5.7 months. RESULTS: Radiographic union was seen in 93.8% (60/64) of patients
      and 95.1% (98/103) of joints using the nitinol staple construct. Radiographic
      union was seen in 90.6% (29/32) of patients and 95.7% (44/46) of joints using the
      nitinol combined staple and screw construct. There was no significant difference
      in radiographic union rate or revision surgery between the 2 groups. Seven
      patients developed nonunion, 4 in the nitinol staple construct group and 3 in the
      staple and screw group. CONCLUSIONS: New-generation nitinol staples were safe and
      effective for hindfoot and midfoot arthrodeses, with a high radiographic union
      rate. The use of a partially threaded screw for additional fixation was not found
      to either significantly increase or decrease radiographic fusion with nitinol
      staple fixation. LEVEL OF EVIDENCE: Level III, comparative cohort study.

PMID- 29073774
TI  - Migraine with brainstem aura: Why not a cortical origin?
AB  - Background Migraine with brainstem aura is defined as a migraine with aura
      including at least two of the following symptoms: dysarthria, vertigo, tinnitus,
      hypacusis, diplopia, ataxia and/or decreased level of consciousness. Aim The aim
      of this study is to review data coming from clinical observations and functional
      mapping that support the role of the cerebral cortex in the initiation of
      brainstem aura symptoms. Results Vertigo can result from a vestibular cortex
      dysfunction, while tinnitus and hypacusis can originate within the auditory
      cortex. Diplopia can reflect a parieto-occipital involvement. Dysarthria can be
      caused by dysfunctions located in precentral gyri. Ataxia can reflect abnormal
      processing of vestibular, sensory, or visual inputs by the parietal lobe.
      Alteration of consciousness can be caused by abnormal neural activation within
      specific consciousness networks that include prefrontal and posterior parietal
      cortices. Conclusion Any symptom of so-called brainstem aura can originate within
      the cortex. Based on these data, we suggest that brainstem aura could have a
      cortical origin. This hypothesis would explain the co-occurrence of typical and
      brainstem aura during attacks and would fit with the theory of cortical spreading
      depression. We propose that migraine with brainstem aura should be classified as
      a typical migraine aura.

PMID- 29073775
TI  - Comparison of Hallux Rigidus Surgical Treatment Outcomes Between Active Duty and
      Non-Active Duty Populations A Retrospective Review.
AB  - BACKGROUND: Our aim in this study was to compare the long-term outcomes of three
      different surgical procedures for the treatment of hallux rigidus (ie,
      cheilectomy, decompressive osteotomy, and arthrodesis) between active duty
      military and non-active duty patients. METHODS: A retrospective review of 80
      patients (95 feet) undergoing surgical treatment for hallux rigidus was
      performed. Telephone survey was used to obtain postoperative outcome measures and
      subjective satisfaction. Additional data recorded and analyzed included age, sex,
      status of patient (active duty or non-active duty), grade of hallux rigidus,
      surgical procedure performed, date of surgery, time to return to full activity,
      ability to return to full duty, and follow-up time postoperatively. RESULTS: The
      decompressive osteotomy group had the highest return-to-duty rate, satisfaction
      rate, and Maryland Foot Scores of all three surgical groups, although these
      differences were not statistically significant. Active duty and non-active duty
      patients did not have statistically significant differences in outcomes measures
      (ie, time to return to full activity, ability to return to full duty,
      satisfaction, or postoperative Maryland Foot Score) in any of the three surgical
      groups. CONCLUSIONS: Decompressive osteotomy, cheilectomy, and first
      metatarsophalangeal joint arthrodesis are all reliable and effective procedures
      for treatment of hallux rigidus in both active duty military and non-active duty
      patients. Active duty military personal have a high rate of returning to their
      prior military activities after surgical treatment of hallux rigidus.

PMID- 29073776
TI  - Distance Between the Anterior Distal Tibial Edge and the Anterior Tibial Artery
      in Distraction and Nondistraction During Anterior Ankle Arthroscopy: A Cadaveric
      Study.
AB  - BACKGROUND: Anterior ankle arthroscopy is widely applied for various
      osteoarthropathies. However, distraction of the ankle may put the anterior tibial
      artery (ATA) at risk of injury during the procedure. The purpose of this study
      was to assess the difference in the distance between the anterior distal tibial
      edge and the ATA in distraction and nondistraction of the ankle with joint space
      expansion by saline injection into the joint. METHODS: Eight whole fresh-frozen
      cadaveric feet (mean age 78.9 years) were used. Barium sulfate suspension was
      injected into the popliteal artery of each specimen, and the distance from 3
      aspects of the anterior distal tibial edge to the ATA was measured to evaluate
      the possibility of damage to the ATA based on computed tomography (CT) scans, in
      ankle distraction and nondistraction, using a traction device developed for
      reproducible ankle positioning inside the CT scanner. RESULTS: The distance
      between the ATA and the most proximal, middle, and distal parts of the anterior
      distal tibial edge was 0.5 mm, 3.9 mm, and 7.4 mm, respectively, without saline
      injection, and 3.7 mm, 7.2 mm, and 11.6 mm, respectively, with saline injection,
      in nondistraction. The distance was 2.2 mm, 5.9 mm, and 9.8 mm, respectively,
      with 5-kg distraction, and 1.7 mm, 5.1 mm, and 8.8 mm, respectively, with 10-kg
      distraction, both with saline injection, respectively. CONCLUSION: The distance
      between the anterior distal tibial edge and the ATA with joint space expansion by
      saline injection into the joint increased, and that distance in distraction of
      the ankle decreased during anterior arthroscopic surgery. CLINICAL RELEVANCE: The
      anatomic relationship of the ATA to its surrounding structures may be at more
      risk without saline injection or with distraction during anterior ankle
      arthroscopy.

PMID- 29073778
TI  - Bronchial artery embolization: first-line option for managing massive hemoptysis.
AB  - Background Today, treatment for hemoptysis is not limited to surgery, and among
      the various options, bronchial artery embolization is regarded as an effective
      approach. Methods In this retrospective study, 179 of 389 patients with massive
      hemoptysis were treated with bronchial artery embolization, without taking into
      account the underlying pathological lesions responsible (bronchiectasis in 41,
      aspergilloma in 29, lung cancer in 25, old tuberculosis in 23, pyothorax in 19,
      others in 23). Results Bronchial artery embolization failed in 12 cases. In the
      167 successful cases, surgery was required in 16 and bronchial occlusion was
      performed in 4; 3 patients died due to recurrent massive hemoptysis. After
      bronchial artery embolization, thoracic surgery for reasons other than hemostasis
      was carried out in 15 patients. Bronchial artery embolization was performed in 31
      patients with hemoptysis who had a history of chest surgery. Four patients
      underwent bronchial occlusion, and immediate hemostasis was achieved in all of
      them. Conclusions For treatment of hemoptysis, bronchial artery embolization is a
      safe and minimally invasive technique that can be performed repeatedly, and
      provides not only short-term but also prolonged effectiveness; thus it can be
      used as a first-line treatment irrespective of the underlying pathological
      lesion. Bronchial occlusion may be useful for emergency hemostasis, but it
      warrants careful follow-up with consideration of additional elective treatment
      such as bronchial artery embolization.

PMID- 29073779
TI  - Mitochondrial NAD+/NADH Redox State and Diabetic Cardiomyopathy.
AB  - SIGNIFICANCE: Diabetic cardiomyopathy (DCM) is a frequent complication occurring
      even in well-controlled asymptomatic diabetic patients, and it may advance to
      heart failure (HF). Recent Advances: The diabetic heart is characterized by a
      state of "metabolic rigidity" involving enhanced rates of fatty acid uptake and
      mitochondrial oxidation as the predominant energy source, and it exhibits
      mitochondrial electron transport chain defects. These alterations promote redox
      state changes evidenced by a decreased NAD+/NADH ratio associated with an
      increase in acetyl-CoA/CoA ratio. NAD+ is a co-substrate for deacetylases,
      sirtuins, and a critical molecule in metabolism and redox signaling; whereas
      acetyl-CoA promotes protein lysine acetylation, affecting mitochondrial integrity
      and causing epigenetic changes. CRITICAL ISSUES: DCM lacks specific therapies
      with treatment only in later disease stages using standard, palliative HF
      interventions. Traditional therapy targeting neurohormonal signaling and
      hemodynamics failed to improve mortality rates. Though mitochondrial redox state
      changes occur in the heart with obesity and diabetes, how the mitochondrial
      NAD+/NADH redox couple connects the remodeled energy metabolism with
      mitochondrial and cytosolic antioxidant defense and nuclear epigenetic changes
      remains to be determined. Mitochondrial therapies targeting the mitochondrial
      NAD+/NADH redox ratio may alleviate cardiac dysfunction. FUTURE DIRECTIONS:
      Specific therapies must be supported by an optimal understanding of changes in
      mitochondrial redox state and how it influences other cellular compartments; this
      field has begun to surface as a therapeutic target for the diabetic heart. We
      propose an approach based on an alternate mitochondrial electron transport that
      normalizes the mitochondrial redox state and improves cardiac function in
      diabetes. Antioxid. Redox Signal. 00, 000-000.

PMID- 29073777
TI  - Neuroprotective effects of orientin on oxygen-glucose deprivation/reperfusion
      induced cell injury in primary culture of rat cortical neurons.
AB  - Orientin (luteolin-8-C-glucoside) is a phenolic compound found abundantly in
      millet, juice, and peel of passion fruit and has been shown to have antioxidant
      properties. In the present study, we explored the effects of orientin on oxygen
      glucose deprivation/reperfusion (OGD/RP)-induced cell injury in primary culture
      of rat cortical neurons using an in vitro model of neonatal ischemic brain
      injury. The reduced cell viability and elevated lactate dehydrogenase leakage
      were observed after OGD/RP exposure, which were then reversed by orientin (10,
      20, and 30 uM) pretreatment in a dose-dependent manner. Additionally, OGD/RP
      treatment resulted in significant oxidative stress, accompanied by enhanced
      intracellular reactive oxygen species (ROS) generation, and obvious depletion in
      the activities of intracellular Mn-superoxide dismutase, catalase, and
      glutathione peroxidase antioxidases. However, these effects were dose dependently
      restored by orientin pretreatment. We also found that orientin pretreatment dose
      dependently suppressed [Ca2+]i increase and mitochondrial membrane potential
      dissipation caused by OGD/RP in primary culture of rat cortical neurons. Western
      blot analysis showed that OGD/RP exposure induced a distinct decrease of Bcl-2
      protein and a marked elevation of Bax, caspase-3, and cleaved caspase-3 proteins;
      whereas these effects were dose dependently reversed by orientin incubation. Both
      the caspase-3 activity and the apoptosis rate were increased under OGD/RP
      treatment, but was then dose dependently down-regulated by orientin (10, 20, and
      30 uM) incubation. Moreover, orientin pretreatment dose dependently inhibited
      OGD/RP-induced phosphorylation of JNK and ERK1/2. Notably, JNK inhibitor SP600125
      and ERK1/2 inhibitor PD98059 also dramatically attenuated OGD/RP-induced cell
      viability loss and ROS generation, and further, orientin failed to protect
      cortical neurons with the interference of JNK activator anisomycin or ERK1/2
      activator FGF-2. Taken together, these results demonstrated that orientin has
      significant neuroprotective effects against OGD/RP-induced cell injury via JNK
      and ERK1/2 signaling pathways in primary culture of rat cortical neurons. Impact
      statement Orientin has been used in traditional eastern medicine and reported to
      possess antioxidant properties. However, the effects of orientin on neonatal
      ischemic brain injury and the underlying mechanisms involved have not been
      studied. Our results showed that orientin exerts significant neuroprotective
      effects on cell injury caused by oxygen-glucose deprivation/reperfusion via the
      JNK and ERK1/2 signaling pathways in primary culture of rat cortical neurons,
      implying the potential therapeutic application of orientin via the suppression of
      oxidative stress and cell apoptosis. This research suggested that orientin may be
      used as a therapeutic and preventive option for newborn cerebral
      ischemia/reperfusion injury.

PMID- 29073781
TI  - Pancytopenia and Fever of Unknown Origin in a 12-Year-Old Boy.

PMID- 29073780
TI  - Continuous Wound Infiltration After Hallux Valgus Surgery.
AB  - BACKGROUND: Hallux valgus surgery is associated with significant early
      postoperative pain. The aim of this study was to investigate the use of
      continuous wound infiltration (CWI) with ropivacaine for pain management after
      hallux valgus surgery. METHODS: In this prospective, randomized, double-blind,
      and placebo-controlled single-center trial, 50 patients undergoing distal
      metatarsal osteotomy for idiopathic hallux valgus were allocated to CWI with
      ropivacaine 2 mg/mL at a rate of 2 mL/h or placebo for 24 hours postoperatively.
      Average and peak pain levels on the verbal numeric rating scale (NRS; 1-10)
      during the first 48 hours after surgery were recorded as primary outcome
      parameters. Secondary outcome parameters included consumption of narcotics,
      clinical outcome, incidence of postoperative complications, and patient
      satisfaction. RESULTS: No significant difference in mean ( P = .596) and peak ( P
      = .353) postoperative pain level was found for CWI with either ropivacaine (mean
      NRS 1.9 +/- 0.8; peak NRS 3.5 +/- 2.0) or placebo (mean NRS 2.0 +/- 0.7; peak NRS
      3.9 +/- 1.7) during the early postoperative course. Furthermore, no significant
      difference between both groups was detected regarding narcotic consumption ( P =
      .354) and all other secondary outcome parameters. Two severe complications (local
      dysesthesia with CWI, catheter accidentally fixed by a suture) and 5 catheter
      dislocations were observed. CONCLUSION: CWI with ropivacaine 2 mg/mL at a rate of
      2 mL/h for 24 hours after hallux valgus surgery did not reduce postoperative pain
      level in an inpatient setting. LEVEL OF EVIDENCE: Level I, prospective randomized
      trial.

PMID- 29073782
TI  - Advances in omics for informed pharmaceutical research and development in the era
      of systems medicine.

PMID- 29073785
TI  - Preventive Effects of Alprostadil Against Contrast-Induced Nephropathy Inpatients
      With Renal Insufficiency Undergoing Percutaneous Coronary Intervention.
AB  - We investigated the preventive effect of alprostadil on contrast-induced
      nephropathy (CIN) in patients with renal insufficiency undergoing percutaneous
      coronary intervention (PCI). A total of 300 patients with creatinine clearance
      (crCl) <=60 mL/min undergoing PCI were randomly assigned to alprostadil or a
      control group. The primary end point was the incidence of CIN defined as an
      increase in serum creatinine (Scr) levels by >=0.5 mg/dL or>= 25% after
      administration of the contrast media within 72 hours. The secondary end points
      were (1) changes in Scr and crCl within 72 hours and (2) the incidence of major
      adverse events during hospitalization. The incidence of CIN was 2.7% (4/150) in
      the alprostadil group, and 8.7% (13/150) in the control group (chi2 = 5.05, P =
      .043).There was no difference regarding the incidence of major adverse events
      during hospitalization between the alprostadil group and control groups (2.7% vs
      4.0%, P = .750). Multivariate logistic regression analysis showed that
      alprostadil was an independent protective factor for CIN (odds ratio = 0.136, 95%
      confidence interval: 0.020-0.944, P = .044). Prophylactic administration of
      alprostadil may prevent CIN in patients with renal insufficiency undergoing PCI.

PMID- 29073786
TI  - Impact of Diabetes Mellitus on Percutaneous Coronary Intervention in Chinese
      Patients: A Large Single-Center Data.
AB  - AIM: To investigate the impact of diabetic status on 2-year clinical outcomes in
      Chinese patients undergoing contemporary percutaneous coronary intervention (PCI)
      treatment. METHODS AND RESULTS: A total of 10 724 consecutive patients underwent
      PCI at Fu Wai Hospital were prospectively collected. Two-year clinical outcomes
      were compared between patients with and without diabetes mellitus (DM). Diabetic
      patients had more baseline clinical risks and more extensive coronary disease.
      During 2-year follow-up, the rates of all-cause death, myocardial infarction
      (MI), revascularization, and major adverse cardiac events (MACE) were
      significantly higher in DM group. After multivariable-adjusted Cox regression
      analysis, DM was an independent risk factor for MACE but not for the individual
      components of MACE. After performing propensity score matching, rates of all
      cause death, MI, revascularization, stroke, stent thrombosis, and MACE were not
      significantly different between the 2 groups, and DM was not predictive of MACE
      and any clinical adverse outcomes. CONCLUSIONS: Diabetic patients who underwent
      PCI had worse prognosis including death and repeat revascularization during 2
      year follow-up, but DM was not an independent risk factor for adverse clinical
      outcomes.

PMID- 29073787
TI  - Sleep Disturbance Following Concussion Is a Risk Factor for a Prolonged Recovery.
AB  - Sleep disturbance is a common problem following concussion. A retrospective chart
      review was conducted at a regional concussion clinic on patients 13 to 18 years
      of age between 2005 and 2011. Statistical analysis evaluated sleep disturbance
      and duration of concussion, as well as the use and effectiveness of melatonin. A
      total of 417 patients met inclusion criteria. One hundred twenty-three (34%)
      reported disturbance in sleep. There was no difference in sleep disturbance based
      on age, gender, or past number of concussions. Sleep disturbance was associated
      with a 3- to 4-fold increase in recovery time. Non-sport-related concussions were
      more likely to be associated with sleep disturbance compared to sport-related
      concussions (45% vs 29%, P = .01). Melatonin improved sleep disturbance in 67% of
      the patients. Evaluating sleep disorders following concussion is an important
      part of the assessment. These findings will help clinicians provide anticipatory
      guidance and treatment for adolescents recovering from concussion.

PMID- 29073788
TI  - Affective temperaments during pregnancy and postpartum period: a click to
      hyperthymic temperament.
AB  - BACKGROUND: Pregnancy and postpartum periods are the main reproductive periods
      during which women experience mood disorders. Affective temperaments are known
      antecedents of mood disorders and their importance is increasing in time for
      early diagnosis and determining risky groups. But data about affective
      temperaments during perinatal period is limited. METHODS: Women during pregnancy
      and perinatal period and healthy controls who are not in perinatal period are
      included in the study. 83 pregnant women in 1st trimester, 94 pregnant women in
      2nd trimester and 115 pregnant women in 3rd trimester; 32 women in 1st month
      postpartum and 89 women in 2nd month postpartum; and 88 healthy non-pregnant
      women with similar ages were evaluated regarding their temperament evaluation of
      Memphis, Pisa, Paris and San Diego auto-questionnaire (TEMPS-A) scores. RESULTS:
      Women in perinatal period had higher scores of hyperthymic temperaments than the
      control group. Women in the 2nd month of postpartum period had also higher
      anxious temperament scores. And women in the second trimester had the highest
      hyperthymic temperament scores. CONCLUSION: Pregnancy and postpartum periods
      correlate with hyperthymic temperament characteristics in women without active
      psychiatric diagnosis. Future studies will help to understand if this is a mental
      quietness or increased risk for bipolarity.

PMID- 29073789
TI  - A new coruleoellagic acid derivative from stems of Rhodamnia dumetorum.
AB  - A new coruleoellagic acid derivative, 3,3',4,4',5'-pentamethylcoruleoellagic acid
      (1) together with nine known compounds, hexamethylcoruleoellagic acid (2), 3,4,3'
      tri-O-methylellagic acid (3), heptaphylline (4), 7-methoxymukonal (5), dentatin
      (6), sinapaldehyde (7), gallic acid (8), 2,6-dimethoxy-4H-pyran-4-one (9) and
      beta-sitosterol (10) were isolated from the stems of Rhodamnia dumetorum. Their
      structures were identified by physical and spectroscopic data (IR, 1D and 2D NMR,
      and MS). Compounds 1, 2 and 7-10 were tested for antibacterial activity against
      six pathogenic bacterial strains (Bacillus cereus, Escherichia coli, Pseudomonas
      aeruginosa, Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and
      Methicillin resistant S. aureus (MRSA)).

PMID- 29073790
TI  - Efficacy of dehydroepiandrosterone (DHEA) supplementation for in vitro
      fertilization and embryo transfer cycles: a systematic review and meta-analysis.
AB  - Dehydroepiandrosterone (DHEA) supplementation might hold some promise in vitro
      fertilization and embryo transfer cycles. However, the results remain
      controversial. We conducted a systematic review and meta-analysis to evaluate the
      efficacy of DHEA in patients for in vitro fertilization. PubMed, EMbase, Web of
      science, EBSCO and Cochrane library databases were systematically searched.
      Randomized controlled trials (RCTs) assessing the effect of DHEA versus placebo
      on in vitro fertilization were included. Two investigators independently searched
      articles, extracted data and assessed the quality of included studies. The
      primary outcomes were clinical pregnancy and live birth rate. Meta-analysis was
      performed using random-effect model. Six RCTs involving 745 patients were
      included in the meta-analysis. Overall, compared with placebo, DHEA
      supplementation was associated with the significant increase in clinical
      pregnancy (OR = 1.45; 95% CI = 1.04-2.03; p = .03), live birth rate (OR = 2.70;
      95% CI = 1.24-5.85; p = .01) and endometrial thickness (Std. mean difference =
      0.67; 95% CI = 0.02-1.32; p = .04) but showed no influence on E2 on hCG day (Std.
      mean difference = 0.69; 95% CI =  -0.46 to 1.85; p = .24), embryos transferred
      (Std. mean difference = 0.42; 95% CI =  -0.04 to 0.88; p = .07) and miscarriage
      rate (OR = 0.43; 95% CI = 0.03-6.66; p = .55). DHEA supplementation could
      significantly improve clinical pregnancy, live birth rate, endometrial thickness
      and retrieved oocytes but failed to alter E2 on hCG day, embryos transferred and
      miscarriage rate.

PMID- 29073792
TI  - Alendronate-loaded, biodegradable smart hydrogel: a promising injectable depot
      formulation for osteoporosis.
AB  - Alendronate (ALN) is a BCS III bone resorption inhibitor, with very poor oral
      bioavailability. Our approach is to develop a minimally invasive thermogelling
      system for prolonged local delivery of ALN. For this, different chitosan-based
      thermogels were developed and characterised in terms of gelation time,
      injectability, pH, viscosity and thermoreversibility. Chitosan/beta
      glycerophosphate (CS/betaGP) hydrogel pursued temperature-dependent,
      thermoreversible gelation behaviour and was thus selected for drug loading.
      Increasing ALN concentration resulted in hydrogels with lower porosity and higher
      density. FTIR and DSC proved interaction between ALN, CS with betaGP. CS/betaGP
      hydrogel ensured controlled ALN release over 45-65 days depending on initial ALN
      loading. Freeze drying improved the shelf-life stability with minor impact on
      thermogelling character. In vivo injection of plain and ALN-loaded hydrogel in
      rats rapidly gelled 15 min post-injection. Based on histological examination, ALN
      loaded thermogel showed less inflammatory response, faster proliferation and
      maturation of granulation tissue relative to plain thermogel. Hydrogels excised
      21-days post-injection proved the biocompatibility and biodegradability of the
      system. The presented chitosan-based thermogel has significant positive
      attributes for site-specific, time-controlled, intra-articular delivery of ALN.

PMID- 29073791
TI  - Downregulation of LncRNA-RP11-317J10.2 promotes cell proliferation and invasion
      and predicts poor prognosis in colorectal cancer.
AB  - OBJECTIVES: Using microarray analysis, we previously showed that many lncRNAs are
      differentially expressed in colorectal cancer (CRC) tissues compared with normal
      tissues, suggesting that lncRNAs may be involved the initiation and progression
      of CRC. In this study, we investigated the expression and function of lncRNA-RP11
      317J10.2 in human CRC tissues and cell lines. METHODS: LncRNA-RP11-317J10.2
      expression level was analyzed in 52 colon cancer and cell lines. We used shRNA to
      knock-down the expression of RP11-317J10.2, and then proliferation assay, colony
      formation assay, Boyden chamber assay, FACS and Kaplan-Meier survival analysis
      were performed to explore the biological effect of RP11-317J10.2. Cyclin D1
      protein level was detected by Western blot. RESULTS: LncRNA-RP11-317J10.2 is
      downregulated in CRC and decreased expression is significantly associated with
      advanced tumor stage, larger tumor size and poor prognosis. RNA interference
      mediated knockdown of lncRNA-RP11-317J10.2 in CRC cells promotes G1-to-S cell
      cycle transition, enhances invasiveness and facilitates cell growth in vitro and
      in mouse tumor xenograft models. Cyclin D1 was upregulated by lncRNA-RP11
      317J10.2 knockdown, and co-expression of cyclin D1-targeting siRNA abrogates the
      pro-tumorigenic effects of lncRNA-RP11-317J10.2 knockdown. CONCLUSIONS: This
      study reveals a crucial role for lncRNA-RP11-317J10.2 in CRC growth and invasion
      via upregulation of cyclin D1 expression and suggests that expression of this
      lncRNA may be a potential prognostic biomarker for CRC.

PMID- 29073793
TI  - Infertility and surrogacy first mentioned on a 4000-year-old Assyrian clay tablet
      of marriage contract in Turkey.
AB  - Mankind has been expressing the breeding topic for thousands of years.
      Reproduction is the primary instinct of human beings and it is a social,
      cultural, medical issue. Demographic infertility is one of them, which is defined
      infertility as the inability to become pregnant with a live birth, within five
      years of regular sexual contact based upon a consistent union status in marriage
      maintaining a desire for a child with the lack of contraceptive use and non
      lactating. A first mentions about infertility and surrogacy is discovered on a
      4000-year-old clay tablet of marriage contract belonging to the Assyrian period
      exhibited at Istanbul Archeology Museum in Turkey. In conclusion, there are many
      different ways to solve infertility problems like surrogacy as mentioned even
      4000 years ago in this Assyrian clay tablet of marriage contract as the first
      time in the literature. Medical treatments in relation to human infertility will
      continue to be the focus of social and cultural debates. Hence, more legislation
      and regulation will come in many countries to control the unauthorized
      exploitation of the patient.

PMID- 29073794
TI  - Porous Titanium Wedges in Lateral Column Lengthening for Adult-Acquired Flatfoot
      Deformity.
AB  - : Lateral column lengthening (LCL) is a common procedure for reconstruction of
      stage II flexible adult-acquired flatfoot deformity (AAFD). The recent
      development of porous titanium wedges for this procedure provides an alternative
      to allograft and autograft. The purpose of this study was to report radiographic
      and clinical outcomes achieved with porous titanium wedges in LCL. A
      retrospective analysis of 34 feet in 30 patients with AAFD that received porous
      titanium wedges for LCL from January 2011 to October 2014. Deformity correction
      was assessed using both radiographic and clinical parameters. Radiographic
      correction was assessed using the lateral talo-first metatarsal angle, the
      talonavicular uncoverage percentage, and the first metatarsocuneiform height. The
      hindfoot valgus angle was measured. Patients were followed from a minimum of 6
      months up to 4 years (mean 16.1 months). Postoperative radiographs demonstrated
      significant correction in all 3 radiographic criteria and the hindfoot valgus
      angle. We had no cases of nonunion, no wedge migration, and no wedges have been
      removed to date. The most common complication was calcaneocuboid joint pain
      (14.7%). Porous titanium wedges in LCL can achieve good radiographic and clinical
      correction of AAFD with a low rate of nonunion and other complications. LEVELS OF
      EVIDENCE: Level IV: Case series.

PMID- 29073795
TI  - Matrix-assisted laser desorption/ionization-time of flight mass spectrometry:
      protocol standardization and database expansion for rapid identification of
      clinically important molds.
AB  - AIM: To standardize the matrix-assisted laser desorption ionization-time of
      flight mass spectrometry protocols and expansion of existing Bruker Biotyper
      database for mold identification. MATERIALS & METHODS: Four different sample
      preparation methods (protocol A, B, C and D) were evaluated. RESULTS: On
      analyzing each protein extraction method, reliable identification and best log
      scores were achieved through protocol D. The same protocol was used to identify
      153 clinical isolates. Of these 153, 123 (80.3%) were accurately identified by
      using existing database and remaining 30 (19.7%) were not identified due to
      unavailability in database. On inclusion of missing main spectrum profile in
      existing database, all 153 isolates were identified. CONCLUSION: Matrix-assisted
      laser desorption ionization-time of flight mass spectrometry can be used for
      routine identification of clinically important molds.

PMID- 29073796
TI  - Death audit in the neonatal ICU of a tertiary care hospital in Bangladesh: a
      retrospective chart review.
AB  - BACKGROUND: Expectant reduction of neonatal mortality and formulation of
      preventive strategies can only be achieved by analysis of risk factors in a
      particular setting. This study aimed to document incidence of neonatal death and
      to analyze the risk factors associated with neonatal death. METHODS: This
      retrospective study was carried out in department of Neonatology, Bangabandhu
      Sheikh Mujib Medical University (BSMMU) over a 12-month period from January to
      December 2015. The newborns that died within 28 d of life were defined as "Cases"
      and "Control" were the surviving newborn discharged to home as healthy. Two birth
      weight and gestational age matched controls were taken for each case. Maternal,
      obstetric, and newborn characteristics were analyzed between both the groups.
      Data analysis was performed using SPSS version 20.0 (SPSS Inc., Chicago, IL). A
      probability of < .05 was considered statistically significant. The strength of
      association was determined by calculating odds ratio and their 95% confidence
      intervals (CIs). RESULTS: During the study period, the proportion of death was
      9.6% (64/612). Both in Chi-square analysis and in logistic regression analysis,
      less than four antenatal visits (odds ratio (OR) 2.78; 95% CI: 1.23-6.28, p =
      .014) and sepsis (OR 2.37; 95% CI: 1.07-5.26, p = .034) were found to be
      independent risk factors for deaths, whereas LUCS found to be protective for
      deaths (OR 0.40; 95% CI: 0.19-0.83, p = .015). CONCLUSION: In conclusion, less
      than four antenatal visits and presence of sepsis were found to be independent
      risk factors whereas LUCS protective of newborn death.

PMID- 29073797
TI  - Features of polycystic ovary syndrome (PCOS) in women with functional
      hypothalamic amenorrhea (FHA) may be reversible with recovery of menstrual
      function.
AB  - OBJECTIVE: Since features of polycystic ovary syndrome (PCOS) have been found to
      be prevalent in women with functional hypothalamic amenorrhea (FHA), we wished to
      determine what happens to these features after recovery of menstrual function in
      FHA Design: Prospective cohort study. Twenty-eight women with FHA and 30 age
      matched ovulatory controls were studied. METHODS: Twenty-eight women with FHA and
      30 age-matched ovulatory controls were studied. We measured serum estradiol, LH,
      FSH, testosterone, DHEAS, anti-Mullerian hormone (AMH), body mass index, and
      ovarian morphology on transvaginal ultrasound. RESULTS: At baseline, 12 of the 28
      women (43%) had increased AMH (>4.7 ng/mL), and higher testosterone and larger
      ovaries compared to the other 16 women with normal AMH. One year after recovery
      of menstrual function, in the 12 women with increased AMH, serum AMH,
      testosterone and ovarian size decreased, while LH and estradiol increased. At one
      year, only one of the 12 women in the high AMH group developed clinical features
      of PCOS. CONCLUSIONS: In the majority of women with FHA who have PCOS-like
      features, these features may be due to the hypothalamic state and appear to be
      reversible. Few women may develop clinical PCOS after recovery.

PMID- 29073798
TI  - Bone marrow derived mesenchymal stem cells transplantation rescues premature
      ovarian insufficiency induced by chemotherapy.
AB  - Premature ovarian insufficiency (POI) is an important cause of infertility and
      also cause menopausal symptoms, which greatly reduced the quality of life for
      women. Hormone replacement therapy (HRT), as an important strategy, improved the
      quality of life for patients, however, the role of HRT in promoting fertility
      remains controversial. Therefore, seeking an optimal regime for POI becomes more
      urgent. In this study, we established POI model induced by CTX and BUS and
      utilized bone marrow derived mesenchymal stem cells (BM-MSCs) transplantation to
      treat the POI. We found that the decrease of estrogen and the increase of FSH
      induced by administration of CTX and BUS were rescued by BM-MSC transplantation.
      H&E staining and TUNEL assay showed that there were more healthy ovarian
      follicles and less apoptosis of ovarian cells after treatment with BM-MSCs.
      Further studies showed that there was an obvious decrease of Bax, p53, and p21
      after transplantation, however, CyclinD2 was increased. In conclusion, our
      results demonstrated that BM-MSCs could restore injured ovarian function.
      Inhibiting apoptosis and promoting residual ovarian cell proliferation may
      contribute to the process.

PMID- 29073799
TI  - Explaining the effects of a decision intervention on mammography intentions: The
      roles of worry, fear and perceived susceptibility to breast cancer.
AB  - OBJECTIVE: This study examines the effects of a mammography decision intervention
      on perceived susceptibility to breast cancer (PSBC) and emotion and investigates
      how these outcomes predict mammography intentions. DESIGN: Randomised between
      subjects online experiment. Participants were stratified into two levels of risk.
      Within each stratum, conditions included a basic information condition and six
      decision intervention conditions that included personalised risk estimates and
      varied according to a 2 (amount of information: brief vs. extended) * 3 (format:
      expository vs. untailored exemplar vs. tailored exemplar) design. Participants
      included 2465 US women ages 35-49. MAIN OUTCOME MEASURES: PSBC as a percentage,
      PSBC as a frequency, worry, fear and mammography intentions. RESULTS: The
      intervention resulted in significant reductions in PSBC as a percentage for women
      in both strata and significant increases in worry and fear for women in the upper
      risk stratum. Of the possible mediators examined, only PSBC as a percentage was a
      consistent mediator of the effect of the intervention on mammography intentions.
      CONCLUSION: The results provide insight into the mechanism of action of the
      intervention by showing that PSBC mediated the effects of the intervention on
      mammography intentions.

PMID- 29073800
TI  - Integrating Medical-Dental Care for Diabetic Patients: Qualitative Assessment of
      Provider Perspectives.
AB  - Globally, periodontal disease and diabetes have achieved epidemic proportions and
      have become a top health care priority. Mutual bidirectional exacerbation of
      these conditions is promoting creation of cross-disciplinary integrated care
      delivery (ICD) models that bridge the traditionally siloed health care domains of
      dentistry and medicine. By engaging focus groups inclusive of both medical and
      dental providers and one-on-one interviews, this qualitative study investigated
      provider knowledgeability, receptiveness, and readiness to engage ICD and sought
      input from the medical-dental primary care practitioner participants on perceived
      opportunities, benefits, and challenges to achieving ICD models for patients with
      diabetes/prediabetes. Statewide regional representation and inclusivity of
      diverse practice settings were emphasized in soliciting participants. Thematic
      analysis of focus group and interview transcripts was undertaken to establish
      current state of the art, gauge receptivity to alternative ICD models, and seek
      insights from practitioners surrounding opportunities and barriers to ICD
      achievement. Forty providers participated, and thematic analyses achieved
      saturation. Providers were well informed regarding disease interaction; were
      receptive to ICD, including implementation of better screening and referral
      processes; and favored improving interdisciplinary communication inclusive of
      access to integrated electronic health records. Perceived barriers and
      opportunities communicated by participants for advancing ICD were documented.

PMID- 29073801
TI  - Management of gastrointestinal complications in hereditary transthyretin
      amyloidosis: a single-center experience over 40 years.
AB  - INTRODUCTION: Hereditary transthyretin amyloidosis (ATTRm amyloidosis) is a rare
      disease caused by the deposition and accumulation of insoluble non-native
      transthyretin fibrils in the body. The disease inevitably results in widespread
      organ disruption, and poor life expectancy. The GI tract is one organ system
      vulnerable to disruption and, although the clinical presentation of the disease
      varies, GI involvement affects most patients with ATTRm amyloidosis. Areas
      covered: This article presents our experience with diagnosing and treating the GI
      symptoms of ATTRm amyloidosis patients at our center over the last 40 years, in
      the Swedish clustering area of the disease. Our aim is to help other physicians
      to better manage GI complications in patients with this rare but widespread
      condition. Expert commentary: GI symptoms are debilitating complications for
      ATTRm amyloidosis patients to experience, yet with the appropriate questioning
      and diagnosis methods, symptomatic treatments of these symptoms can be
      implemented to provide relief. Further, patients with fewer GI complications and
      a good nutritional status are also better candidates for liver transplantation
      which, in selected cases, is the best disease-modifying treatment of ATTRm
      amyloidosis to date.

PMID- 29073802
TI  - Long-term treatment outcome for adolescents with temporomandibular pain.
AB  - OBJECTIVES: This study aims to evaluate long-term, self-perceived outcome in
      adulthood for individuals treated as adolescents for temporomandibular disorder
      (TMD) pain in two previous randomized controlled trials (RCTs). MATERIALS AND
      METHODS: The study included 116 subjects (81% females) treated for frequent TMD
      pain in two separate RCTs 5-21 (M = 14.8, SD =4.9) years previously. Treatment
      consisted of occlusal appliance (OA) (n = 41, 35.3%) or relaxation training (RT)
      combined with information for the control (Co) group (n = 50, 43.1%), both
      compared to non-responders receiving additional, sequential treatment (ST) in a
      crossover study (n = 25, 21.6%). Participants answered a questionnaire on their
      experience of frequency and intensity of TMD pain impaired chewing capacity and
      daily social activities, help-seeking behaviour and treatment, general health,
      other pain, and depressive symptoms. RESULTS: Older participants reported lower
      levels of frequency and intensity of TMD pain, impairment, and depressive
      symptoms, as well as better general health. Females reported more frequent and
      more intense TMD pain, greater impairment and more often reported 'other pain'
      compared to males. Non-responders receiving ST experienced significantly more
      TMD, and other pain and higher impairment levels compared to other groups. Those
      treated with an OA had sought additional treatment significantly less often since
      the RCTs than ST and RT/Co-treated individuals. CONCLUSIONS: Adolescents treated
      with OA showed somewhat better sustained improvement over the extended follow-up
      period than those treated with RT/Co. Non-responders to treatment and females
      exhibited a poorer outcome. These groups need particular attention and extended
      or different treatments to achieve a better long-term outcome.

PMID- 29073803
TI  - The usefulness of a single arm cuff oscillometric method (Arteriograph) to assess
      changes in central aortic blood pressure and arterial stiffness by
      antihypertensive treatment: results from the Doxazosin-Ramipril Study.
AB  - PURPOSE: Inhibition of the renin-angiotensin system may have effects on vascular
      structure and function beyond the effects on blood pressure (BP) reduction. We
      studied the ability of a single arm cuff oscillometric method (Arteriograph,
      TensioMed, Hungary) to assess effects of antihypertensive treatment on BP and
      arterial stiffness. Furthermore, this technique was compared to pulse wave
      analysis and applanation tonometry (SphygmoCor, AtCor Medical, Australia).
      MATERIALS AND METHODS: Brachial and aortic BP, augmentation index (AIx), and
      carotid-femoral pulse wave velocity (PWV) was simultaneously assessed by both
      techniques in 71 untreated hypertensive patients. Thereafter, 58 completed double
      blind randomized treatment for 12 weeks with ramipril or doxazosin. RESULTS:
      Treatment (assessed by the Arteriograph) reduced aortic more than brachial
      systolic BP (-13.2 vs. -11.2 mm Hg; p = .002) and improved all indices of
      arterial stiffness. This greater reduction in aortic to brachial systolic BP was
      more marked by ramipril than by doxazosin (-20.9 and -17.1 vs. -4.3 and -4.2 mm
      Hg; p = .006), with a similar trend for AIx (-6.2 vs. -2.2%; p = .058). Both
      devices showed correlations for aortic and brachial systolic and diastolic BP and
      AIx (r = 0.75-0.86, all p < .001), while agreement for PWV was weaker (r = 0.28;
      p = .043). The Arteriograph generally recorded higher values for aortic BP and
      AIx than the SphygmoCor. CONCLUSIONS: Antihypertensive treatment reduced aortic
      systolic BP more than brachial BP and improved arterial stiffness. Blocking the
      renin-angiotensin system may have additional effects beyond BP reduction. We
      demonstrate the feasibility of the Arteriograph to monitor changes in BP and
      arterial stiffness by treatment.

PMID- 29073804
TI  - Fabrication of self-assembled folate-biotin-quaternized starch nanoparticles as
      co-carrier of doxorubicin and siRNA.
AB  - In this paper, the starch was firstly modified by quaternary reagent to obtain
      cationic starch. Then self-assembled folate-biotin-quaternized starch
      nanoparticles were prepared by a one-pot synthesis via N,N'
      dicyclohexylcarbodiimide/N-hydroxysuccinimide/4-dimethylaminopyridine-mediated
      esterification reaction. The physicochemical properties of the prepared folate
      biotin-quaternized starch nanoparticles were characterized. The average diameter
      of folate-biotin-quaternized starch nanoparticles was 109 nm with polydispersity
      index of 0.183 and zeta potential of 28.59 mV. The folate-biotin-quaternized
      starch nanoparticles were used as co-carrier of siRNA and doxorubicin with
      satisfactory drug loading capacity (6.98%) and encapsulation efficiency (69.66
      %), and siRNA could be efficiently encapsulated at 40/1 weight ratio of
      doxorubicin/folate-biotin-quaternized starch nanoparticles to siRNA. The folate
      biotin-quaternized starch nanoparticles could effectively protect siRNA from
      degradation of serum RNAase for up to 48 h. The release characteristics of
      doxorubicin and siRNA from folate-biotin-quaternized starch nanoparticles were
      studied in different pH environment and the release behaviors of two drugs were
      all pH sensitive. The folate-biotin-quaternized starch nanoparticles as a
      potential co-carrier of anticancer agents and gene drugs was expected to achieve
      future practical application in vitro and in vivo.

PMID- 29073805
TI  - Comparison of the effectiveness of a PAMG-1 test and standard clinical assessment
      in the prediction of preterm birth and reduction of unnecessary hospital
      admissions.
AB  - PURPOSE: The purpose of this study is to first compare the performance of the
      PAMG-1 biomarker test to that of standard clinical assessment (SCA) for the risk
      assessment of spontaneous preterm delivery (sPTD) among women with symptoms of
      preterm labor (PTL) and then calculate the potential impact on unnecessary
      admission reduction. MATERIALS AND METHODS: Patients of gestational age 240/7
      366/7 with PTL symptoms, cervical dilatation <=3 cm, no intercourse within 24 h,
      and clinically intact membranes were recruited consecutively into this
      prospective observational study. Specificity (SP), sensitivity (SN), positive
      predictive value (PPV), and negative-predictive value (NPV) for the PAMG-1 test
      and SCA, for which a positive result was defined as patient admission, for
      predicting spontaneous delivery <=7 and <=14 d of presentation were calculated.
      RESULTS: One hundred and forty-eight patients were included in the analysis, 132
      of which had both SCA and PAMG-1 results available. For the prediction of sPTD
      <=7 d for SCA and PAMG-1, the PPV and NPV were 10% and 100%, and 71% and 98%,
      respectively. For prediction of sPTD <=14 d for SCA and PAMG-1, the PPV and NPV
      were 14% and 100%, and 86% and 96%, respectively. Sixty-one per cent (81/132) of
      patients were admitted for treatment and/or observation. CONCLUSION: Our study
      reinforces the critical role of the PAMG-1 biomarker test to aid in risk
      assessment of imminent spontaneous preterm delivery in patients with symptoms of
      PTL. The PAMG-1 test was found to be statistically superior to standard clinical
      assessment alone, with respect to specificity. Based on our data, the
      introduction of a PAMG-1 test result into clinical decision making could reduce
      up to 91% of unnecessary admissions for women presenting with threatened preterm
      labor.

PMID- 29073806
TI  - Are Well-Informed Potential Trial Participants More Likely to Participate?
AB  - Bearing in mind the importance of the informed consent, flaws in this process may
      be a barrier to participants' recruitment. Our objective was to determine the
      relationship between the degree of comprehension of the informed consent document
      plus the importance given to individual elements by potential participants of a
      hypothetical trial and their willingness to participate in such trials. We
      performed an Online Survey simulating an emergency department trial recruitment,
      posteriorly evaluating participants' ratings of importance and self-assessed
      comprehension of specific topics of the informed consent document. Only 10% of
      the sample read the entire document. Some specific topics were associated with
      willingness to participate in the hypothetical trial, but simple composite
      additive scores of comprehension and importance were not. We concluded that
      participants in general do not read the entire informed consent document and that
      importance given to specific topics may influence willingness to participate.

PMID- 29073807
TI  - An Assessment of a Shortened Consent Form for the Storage and Research Use of
      Residual Newborn Screening Blood Spots.
AB  - As state newborn screening programs develop approaches to parental permission for
      the storage and use of residual dried newborn screening samples, it is important
      to understand how the public comprehends the consent elements. Focus groups in
      Utah, California, and Michigan ( n = 7 groups, 69 participants) were conducted to
      evaluate the language on a shortened consent form. Outcomes from the analysis
      included barriers to conceptualizing biospecimen research, the overly cautious
      tone and awkwardness of the consent form, and perceptions of community versus
      individual benefit. This research offers insight on public response to, and
      comprehension of, commonly used consent language for the storage and use of dried
      blood spot research in a shortened consent form.

PMID- 29073809
TI  - Pregnancy and delivery with an intrauterine device in situ: outcomes in the
      National Inpatient Sample Database.
AB  - BACKGROUND: Pregnancy with intrauterine device in place is rare and there are
      limited data that exist regarding associated perinatal outcomes. OBJECTIVE: The
      objective of this study is to determine the association between presence of an
      intrauterine device during pregnancy and spontaneous abortion, induced abortion,
      and preterm or small for gestational age delivery outcomes. STUDY DESIGN: The
      National Inpatient Sample database was analyzed for the years 2010 and 2011.
      Maternal records with an intrauterine device in situ during delivery were
      identified using International Classification of Diseases, Ninth Revision,
      diagnostic codes. Primary outcome was incidence of spontaneous abortion.
      Secondary outcomes were incidence of induced abortion, preterm delivery, and
      small for gestational age. Data were analyzed using Chi-square and Fisher's exact
      tests to calculate odds ratios (ORs) of abortion in association with intrauterine
      device in situ during pregnancy. Maternal birth records were further analyzed for
      adverse neonatal outcomes using logistic regression models, controlling for
      possible confounding variables. RESULTS: The data included 8,597,284 maternal
      birth records; 0.02% with an intrauterine device in situ. Patients with an
      intrauterine device in situ experienced a higher frequency of the pregnancy
      ending in spontaneous abortion (OR: 7.15; 95% confidence interval (CI): 5.06
      10.09; p < .001) and induced abortion (OR: 23.12; 95% CI: 15.55-34.36; p < .001)
      than patients without an intrauterine device in place. Adjusted odds ratio for
      preterm delivery among women with an intrauterine device in situ was 2.04 (95%
      CI: 1.71-2.43; p < .001) compared with women without an intrauterine device, and
      adjusted odds ratio for delivery of a small for gestational age infant among
      intrauterine device cohort was 0.56 (95% CI: 0.34-0.92; p = .022), after
      controlling for associated demographic and clinical variables. CONCLUSION: The
      presence of an intrauterine device in situ during pregnancy was associated with
      increased spontaneous and induced abortions, and increased incidence of delivery
      of a preterm, but not small for gestational age infant.

PMID- 29073808
TI  - Whole-Body Biodistribution, Dosimetry, and Metabolite Correction of
      [11C]Palmitate: A PET Tracer for Imaging of Fatty Acid Metabolism.
AB  - INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission
      tomography (PET)/computed tomography in basic metabolism studies, only personal
      communications regarding dosimetry and biodistribution data have been published.
      METHODS: Dosimetry and biodistribution studies were performed in 2 pigs and 2
      healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies
      were performed in 40 participants (healthy and with type 2 diabetes) under basal
      and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches
      and subsequently compared: Indirect [11C]CO2 release and parent [11C]palmitate
      measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid
      uptake was calculated in a patient cohort using input functions derived from
      individual metabolite correction compared with population-based metabolite
      correction. RESULTS: In humans, mean effective dose was 3.23 (0.02) uSv/MBq, with
      the liver and myocardium receiving the highest absorbed doses. Metabolite
      correction using only [11C]CO2 estimates underestimated the fraction of
      metabolites in studies lasting more than 20 minutes. Population-based metabolite
      correction showed excellent correlation with individual metabolite correction in
      the cardiac PET validation cohort. CONCLUSION: First, mean effective dose of
      [11C]palmitate is 3.23 (0.02) uSv/MBq in humans allowing multiple scans using
      ~300 MBq [11C]palmitate, and secondly, population-based metabolite correction
      compares well with individual correction.

PMID- 29073811
TI  - Social and Psychological Factors Related to Risk of Eating Disorders Among High
      School Girls.
AB  - Prevalence of eating disorders (EDs) has increased among adolescents in Arabic
      and Western countries. The purposes are to identify the risk of ED and
      psychosocial correlates of risk of ED among high school girls in Jordan. The
      researchers employed a cross-sectional, correlational design using 799 high
      school girls from governmental and private schools in the central region of
      Jordan. The results indicate that prevalence of the risk of ED was 12%. The risk
      of ED had significant and positive correlation with body shape dissatisfaction,
      self-esteem, psychological distress, and pressure from family, peers, and media (
      p < .001). Body shape dissatisfaction, low self-esteem, negative peer pressure,
      and being young were significant predictors of the risk of EDs. Risk of ED is
      highly prevalent among high school girls, and school nurses need to adopt a model
      of care addressing the risk factors while caring for high school girls.

PMID- 29073810
TI  - Reduced Field of View Diffusion Tensor Imaging and Fiber Tractography of the
      Pediatric Cervical and Thoracic Spinal Cord Injury.
AB  - The aim of this study is to assess the utility and effectiveness of diffusion
      tensor imaging (DTI) and diffusion tensor tractography (DTT) of the entire
      pediatric cervical and thoracic spinal cord toward discrimination of typically
      developing (TD) controls and subjects with spinal cord injury (SCI). A total of
      43 pediatric subjects, including 23 TD subjects ranging in age from 6 to 16 years
      old and 20 subjects with SCI ranging in age from 7 to 16 years, were recruited
      and scanned using a 3.0 Tesla magnetic resonance scanner. Reduced field of view
      diffusion tensor images were acquired axially to cover the entire spinal cord
      across two slabs. For DTI analysis, motion correction was performed by
      coregistration of the diffusion-weighted images to the reference image (b0).
      Streamline deterministic tractography results were generated from the
      preprocessed data. DTI and DTT parameters of the whole cord, including fractional
      anisotropy (FA), mean diffusivity (MD), tract length, and tract density, were
      calculated, averaged across the whole spinal cord, and compared between the TD
      and SCI groups. Statistically significant decreases have been shown in FA (TD =
      0.46 +/- 0.11; SCI = 0.37 +/- 0.09; p < 0.0001) and tract density (TD = 405.93 +/
      243.84; SCI = 268.90 +/- 270.34; p < 0.0001). However, the mean length of tracts
      and MD did not show significant differences. When investigating differences in
      DTI and DTT parameters above and below the injury site, it was shown that the FA
      and tract density in patients with cervical SCI decreased significantly in the
      thoracic region. An identical trend was observed in the cervical region for
      patients with thoracic SCI as well. When comparing TD and SCI subjects, FA and
      tract density were the most sensitive parameters in detecting functional changes
      of the spinal cord in chronic pediatric SCI. The results show that both DTI and
      DTT have the potential to be imaging biomarkers in the diagnosis of SCI.

PMID- 29073812
TI  - Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant
      protein 1 as biomarkers for lupus nephritis in Colombian SLE patients.
AB  - Background Information regarding urinary biomarkers in Mestizo and Afro-Latin
      American patients is very limited. We investigated whether levels of urinary
      neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant
      protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus
      nephritis among Latin-American systemic lupus erythematosus (SLE) patients.
      Methods SLE patients meeting the revised American College of Rheumatology
      classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1
      were measured using a commercial ELISA kit. Serum anti-C1q antibodies were
      measured by ELISA. SLE activity was measured with the systemic lupus
      erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to
      compare data and Spearman's rank correlations were used to examine associations
      between continuous variables. In addition, receiver operating characteristic
      curves were performed. Results One hundred and twenty SLE patients were recruited
      (87% women) with a median age of 32.8 +/- 12.1 years and median disease duration
      of 7.3 +/- 6.9 years. Afro-Latin-Americans had a significantly higher prevalence
      of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers
      were significantly higher in patients with lupus nephritis than in patients
      without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly
      higher in patients with active lupus nephritis than in inactive lupus nephritis.
      Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A
      receiver operating characteristic curve for urinary biomarkers for lupus
      nephritis in all SLE patients showed a good level of sensitivity and specificity.
      Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in
      addition to anti-C1q antibodies were useful biomarkers for the identification of
      renal involvement and discrimination of active lupus nephritis among patients
      with renal disease.

PMID- 29073813
TI  - Silencing thioredoxin1 exacerbates damage of astrocytes exposed to OGD/R by
      aggravating apoptosis through the Actin-Ras2-cAMP-PKA pathway.
AB  - PURPOSE OF THE STUDY: Induction of endogenous antioxidants is one of the key
      molecular mechanisms of cell resistance to hypoxia/ischemia. Thioredoxin1 (Trx1)
      is a small multifunctional ubiquitous antioxidant with redox-active dithiol and
      plays an important role in cell apoptosis through mitochondrial apoptosis
      pathways. The specific role of Trx1 in ischemia-reperfusion induced astrocyte
      apoptosis, however, remains unclear. MATERIALS AND METHODS: In this study, we
      investigated the effect of Trx1 on apoptosis of astrocyte using an in vitro
      oxygen-glucose deprivation/reoxygenation (OGD/R) model which mimics
      ischemic/reperfusion conditions in vivo. The astrocytes prepared from newborn
      Sprague-Dawley rats were exposed to OGD for 4 h followed by reoxygenation for 24
      h. Next, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was
      used to assess cell viability while cell damage was assessed by lactate
      dehydrogenase (LDH). RESULTS: We found that OGD/R increased cell death as well as
      the expression of Trx1 and that the interference of Trx1 further aggravated
      astrocyte damage under OGD/R condition. Furthermore, we detected an increase in
      the intracellular expressions of Ras2, cAMP, and PKA under OGD/R condition, which
      paralleled cell injury. CONCLUSIONS: Notably, the deletion of Trx1 exacerbated
      astrocyte apoptosis via the Ras2-cAMP-PKA signaling pathway. We concluded that
      Trx1 protects astrocytes against apoptotic injury induced by OGD/R, and this
      protective effect may be partly related to the Ras2-cAMP-PKA signaling pathway.

PMID- 29073814
TI  - Selective versus non-selective removal for dental caries: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: Selective and non-selective methods for caries removal were
      controversial so far, thus we aimed to compare the efficacy of selective and non
      selective caries removal by conducting meta-analysis of randomized controlled
      trials (RCTs). MATERIALS AND METHODS: Eligible RCTs studies comparing selective
      caries removal with non-selective caries removal were retrieved by searching
      PubMed, EMBASE and Cochrane Library till 15 July 2017. The pooled odds ratios
      (ORs) with 95% confidence intervals (CIs) were calculated for outcome indictors,
      including pulpal exposure, pulpal symptoms and failure using Inverse variance
      random effects or Mantel-Haenszel-fixed effects models. RESULTS: Totally, seven
      studies were eligible for the meta-analysis. Compared with the non-selective
      caries removal group, the risk of pulpal exposure was significantly reduced in
      the selective caries removal group (OR = 0.11, 95% CI: 0.04-0.30). No significant
      difference was observed in pulpal symptoms (OR = 0.79, 95% CI: 0.30-2.12) and
      failure (OR = 1.40, 95% CI: 0.69-2.84) between the groups. CONCLUSIONS: The
      efficacy of selective caries removal appears comparable to that of non-selective
      caries removal in children, with similar pulpal symptoms and failure, but
      selective caries removal may result in a low incidence of pulpal exposure.
      However, larger-scale RCTs with long-term follow-up are required to confirm this
      conclusion.

PMID- 29073816
TI  - Tailoring Computer-Based Training for Latino Immigrant Workers: Pilot Test of the
      NIOSH Mouse Tutorial.
AB  - An interactive tutorial on using a mouse for first-time computer users was
      developed as part of a training CD-ROM tailored for Latino immigrant workers in
      trenching and excavation. It was designed for Spanish-speaking users with varying
      levels of formal education. The tutorial was tested in focus groups with workers
      who had little or no previous experience using a computer. Findings revealed that
      while users with less than a fourth-grade education and/or low proficiency in
      Spanish had some difficulties with the tutorial, they still scored above 67
      percent on the performance evaluation; participants with at least a fourth-grade
      education (the majority) completed it with minimal assistance and scored 80%-100%
      on the performance evaluation. Feedback from participant focus groups following
      the computer sessions supported these findings. The results of this study suggest
      that computer-based training may be able to be made accessible for low computer
      literacy Latino immigrant workers, if it is tailored to their needs.

PMID- 29073815
TI  - Effect of esterified hyaluronic acid as middle ear packing in tympanoplasty for
      adhesive otitis media.
AB  - OBJECTIVES: The goal of this study was to evaluate the effects of middle ear
      packing agents (MEPA) on post-operative hearing improvement and complications
      after tympanoplasty in patients with adhesive otitis media (OM). MATERIALS AND
      METHODS: Patients with adhesive OM who underwent tympanoplasty surgery were
      enrolled in the study between January 2012 and January 2015. A total of 205
      patients who received canal wall-down tympanoplasty with ossicular chain
      reconstruction were randomized into one of the three groups with different MEPA.
      Group 1 (n = 72) received MeroGel as the MEPA, Group 2 (n = 64) cartilage, and
      Group 3 (n = 69) both. Air conduction (AC) and bone conduction (BC) thresholds at
      0.5, 1, 2, and 4 kHz were measured, and air-bone gaps (ABG) were analyzed before
      and after the surgery for each patient. RESULTS: Mean pre- and post-operative ABG
      was 30.9 dB and 17.6 dB in Group 1, 31.4 dB and 21.9 dB in Group 2, and 32.2 dB
      and 19.1 dB in Group 3. The ABG closure was 13.3 +/- 7.5 in Group 1, 9.5 +/- 5.9
      in Group 2, and 13.1 +/- 9.3 in Group 3. The improvement of ABG after surgery was
      statistically significant in all three groups (p < .05). The ABG closure was
      statistically significantly smaller in Group 2 than in other two groups (p <
      .05). CONCLUSIONS: Tympanoplasty using esterified hyaluronic acid (i.e. MeroGel)
      or cartilage as the MEPA resulted in improved hearing for patients with
      conductive hearing loss due to adhesive OM. Using MeroGel as the MEPA appeared to
      achieve a better post-operative outcome than using cartilage.

PMID- 29073817
TI  - Twelve tips to promote gender equity in international academic medicine.
AB  - Gender inequity in academic medicine remains an important issue worldwide, with
      more female faculty entering academic medicine internationally. Some academic
      institutions have initiated programs and created policies to promote gender
      equity, but disparities remain in faculty numbers, promotions rates, research
      productivity and access to funding and resources. We offer 12 tips for best
      practices in the broad domains of faculty recruitment, retention and scholarship,
      promotion and leadership that institutions and individual faculty can adopt to
      promote gender equity. While the 12 tips form a comprehensive approach, each tip
      can be implemented individually depending on institutional needs and culture.
      Each tip includes practical advice for implementation supported by a successful
      example from the literature.

PMID- 29073818
TI  - Testing the Discriminant and Convergent Validity of the World Health Organization
      Six-Item Adult ADHD Self-Report Scale Screener Using the Stockholm Public Health
      Cohort.
AB  - OBJECTIVE: The World Health Organization (WHO) Adult ADHD Self-Report Scale
      (ASRS) is intended to measure population prevalence of ADHD. The short version
      ASRS-6 has yet not been validated in a population setting. Our aim was to examine
      the validity of the ASRS-6 in a general population. METHOD: We used the Stockholm
      Public Health Cohort 2014. The convergent validity was assessed using item
      response theory (IRT). The discriminant validity was assessed by examining the
      correlation between the ASRS and known correlates. RESULTS: The ASRS-6 was
      unidimensional albeit with hyperactivity and impulsivity items fitting less good.
      IRT analysis showed that the item difficulty ranged between easy to hard and that
      the four items on inattention had good or very good discriminatory ability.
      Correlates were all in the expected direction. CONCLUSION: The ASRS-6 has
      adequate validity in the general population but reflects the duality of ADHD
      having both inattention and hyperactivity/impulsivity as sufficient and non
      necessary criteria.

PMID- 29073819
TI  - Evaluation of hair cortisol and cortisone change during pregnancy and the
      association with self-reported depression, somatization, and stress symptoms.
AB  - Hair cortisol levels are used to measure long-term stress, while its inactive
      metabolite cortisone is often not assessed. We measured hair cortisol
      concentrations (HCC) and hair cortisone concentrations (HCNC) via liquid
      chromatography quadrupole linear ion trap mass spectrometry (LC-MS3) in 62
      pregnant women who participated in the LIFE CHILD STUDY in their 2nd and 3rd
      trimester between 12/2011 and 11/2014. Sociodemographic factors, pregnancy
      related factors, and hair characteristics were assessed. Degree of severity of
      depression, somatization, and stress were evaluated in both trimesters with a
      self-reported Patient Health Questionnaire (PHQ). Multivariate regression
      analyses were conducted between HCC and potential influencing factors, as well as
      with subscales of the PHQ, with HCNC and with the ratio of HCNC to HCC. Spearman
      correlation coefficients were calculated between steroid concentrations and
      subscale scores of the PHQ, as well as between the log2-fold change in HCC and
      HCNC and the change in PHQ subscale scores. HCC increased 1.3-fold and HCNC
      increased 1.5-fold by the 3rd trimester. HCNC was more than three times higher
      than HCC in both trimesters. We found significant associations of PHQ subscores
      with HCNC. The PHQ depression score was negatively correlated with HCNC in the
      2nd trimester (p < .05). The PHQ stress score change was negatively correlated
      with the fold change of HCNC (p < .05) and with the change in the ratio of HCNC
      to HCC (p < .001). Our study suggests an association of cortisol/cortisone
      metabolism with self-reported stress in the 2nd and 3rd trimester of pregnancy.
      Since associations with PHQ subscores were only found with cortisone or the ratio
      of cortisone to cortisol, but not with cortisol alone, both cortisone and
      cortisol should be used as a marker for stress in pregnant woman.

PMID- 29073820
TI  - Acute Changes in Plasma Total Tau Levels Are Independent of Subconcussive Head
      Impacts in College Football Players.
AB  - Athletes in contact sports sustain repetitive subconcussive head impacts in a
      brief window, yet neurophysiological sequelae from repetitive subconcussion
      remain unclear. This prospective longitudinal study examined a relationship
      between changes in plasma Tau protein levels and subconcussive impact kinematic
      data in 23 Division I collegiate football players during a series of pre-season
      practices. Plasma measures for Tau and S100beta proteins, symptom scores, and
      near point of convergence were obtained at pre-season baseline and pre-/post
      practices. During each practice, impact frequency and linear and rotational head
      accelerations were recorded via an accelerometer-embedded mouth guard. There were
      significant elevations in plasma Tau levels at all post-practice time-points,
      compared with those of pre-practice and baseline levels. However, the highest
      degree of elevation in plasma Tau was observed after the first practice, for
      which players sustained the lowest number of hits and magnitudes for these hits.
      Subconcussive impact exposure during practice (e.g., head impact frequency and
      magnitude) did not predict increased plasma Tau levels. Concussion history and
      years of football experience also were unrelated to changes in plasma Tau levels.
      Increases in plasma Tau levels were associated with increases in S100beta levels
      only after the first practice. There were no significant associations between
      changes in Tau levels, symptom scores, or near point of convergence. These data
      suggest that the changes in levels of circulating Tau protein were independent of
      subconcussive head impact exposure, pointing to the possibility that other
      factors may have played roles in changes in plasma Tau levels.

PMID- 29073821
TI  - Widowhood in the Israeli Arab Muslim Society.
AB  - Adjustment of Israeli Arab Muslim widows to the traumatic loss of their husbands
      was examined by comparing their reported ways of coping with those of married
      women of their community by means of the Two-Track-Bereavement Model.
      Participants included 93 widows and 86 comparable married women who were mostly
      middle aged and of middle class. We hypothesized that widows will express
      concurrently greater suffering and higher resilience to adverse life events
      compared with married women. It was hypothesized further that positive and close
      relations to a deceased husband will be reported by Arab widows as well as Arab
      married women. However, positive relationships of married women will correlate
      with their own coping supporting attributes, whereas positive relations of widows
      to their deceased husband will not be associated with their individual
      characteristics. Results indicated a fourfold factor structure of the bereavement
      and coping scale which differed from those obtained by Israeli Jewish women and
      generally supported these hypotheses. It appears that traumatic loss of a husband
      may enhance widows' resilience.

PMID- 29073822
TI  - Equine Exercise in Younger and Older Adults: Simulated Versus Real Horseback
      Riding.
AB  - Horseback riding is an effective exercise for improving postural control and
      balance. To reduce costs and improve accessibility, simulated horseback riding
      has been developed; but no differential effects of simulated and real horseback
      riding on muscle activation patterns in older adults have been studied. Thus, we
      compared muscle activation patterns for older and younger adults engaged in real
      and simulated horseback riding exercises, using surface electromyography
      recordings of the erector spinae, rectus abdominis, internal oblique abdominis,
      and rectus femoris muscles. We recorded muscle activity for three riding
      patterns: walk, slow trot, and fast trot. Muscle activation was uniformly higher
      for simulated (vs. real) horseback riding and increased from the walking pattern
      through slow and fast trot. There was no age effect, but among older
      participants, muscle activation was higher for simulated (vs. real) horseback
      riding across all gait types. Simulated and real riding produced a similar
      pattern of muscle activation of the thigh and trunk. These results demonstrate
      that simulated horseback riding can be an effective alternative to actual riding
      for increasing trunk and thigh muscle activation and improving postural control
      and balance, perhaps especially among older adults.

PMID- 29073823
TI  - Mechanical restraint and characteristics of patient, staff and shifts in a
      psychiatric ward.
AB  - BACKGROUND: The use of coercion is a balance between depriving the patients'
      autonomy and dignity and preventing endangerment of the body or health of self or
      others. It is of importance to obtain more knowledge about mechanisms leading to
      mechanical restraint in the attempt of reducing it. OBJECTIVE: To analyse for
      associations between incidence of mechanical restraint (MR) and staffing level,
      staff demographics, patient characteristics, type of shift (day/evening/night)
      and change of shifts. METHOD: A naturalistic descriptive method was used to study
      cases of MR in a psychiatric ward. Data for each case of MR was obtained from an
      electronic reporting system. Care workers from each shift were identified using
      duty rosters. Analyses included binary logistic regression analyses. RESULTS: In
      82% of the 114 cases of MR, the patient was diagnosed with personality disorders.
      In the multiple regression analysis, a significant association was found between
      the use of MR and the presence of male care workers on the ward (OR:1.44, 95% CI:
      1.01-2.05; p = .04). Moreover, MR was associated with evening shifts, compared
      with day and night shifts (OR =1,29, 95% CI: 1.14-2.57, p = .01). Besides, months
      from January to December was associated with a decrease in MRs (OR: 0.88, 95% CI:
      0.83-0.94; p = 7.3 E-6). No significant associations were found between MR and
      staffing level or experience. CONCLUSIONS: MR was associated with evening shifts,
      higher number of male care workers on duty and a decrease from January to
      December.

PMID- 29073824
TI  - Twelve tips for integrating leadership development into undergraduate medical
      education.
AB  - Healthcare systems need effective leadership. All healthcare professionals can
      and should "learn to lead" and this requires a clear focus on leadership
      development from the earliest stages of a career. Within medicine, undergraduate
      students should be provided with opportunities to thrive and develop their skills
      in terms of leadership, management and followership. Drawing from the existing
      evidence base, the authors' expertise and the latest "thought leadership", these
      12 tips provide practical guidance to universities and associated provider
      organizations, and to academic and clinical faculty, on how to integrate
      leadership development into their undergraduate medical programs. These 12 tips
      will help educators provide medical education that incorporates leadership as a
      core part of a professional's identity, and help students gain a deeper
      understanding of themselves and the teams, organizations and system they work
      within.

PMID- 29073825
TI  - Myasthenia gravis and chronic inflammatory demyelinating polyneuropathy in the
      same patient - a case report.
AB  - PURPOSE: To investigate the clinical character, diagnosis and treatment of
      chronic inflammatory demyelinating polyneuropathy accompanying myasthenia gravis
      so as to improve the understanding of such diseases. MATERIALS AND METHODS: A
      case of chronic inflammatory demyelinating polyneuropathy combined with
      myasthenia gravis were analyzed retrospectively with review of the literature.
      RESULTS: This man was presented with chronic progressive sensory symptoms,
      flaccid tetraparesis, areflexia and protein-cell dissociation of cerebrospinal
      fluid. Nerve conduction study was indicative of demyelinating neuropathy. He was
      suspected as chronic inflammatory demyelinating polyneuropathy and treated with
      high-dose glucocorticoids. However, his condition worsened. Four months later, he
      was admitted and was diagnosed as combination of chronic inflammatory
      demyelinating polyneuropathy and myasthenia gravis. Good clinical results were
      observed after he was treated with pyridostigmine bromide, prednisone and
      mycophenolate mofetil. CONCLUSIONS: This case warns clinicians to be aware of
      these two diseases presenting in the same patient, and the possible implications
      on treatment choices. A common immunological abnormality might exist in this rare
      association, but it still remains unknown.

PMID- 29073826
TI  - Association of QRS duration with left ventricular volume and ejection fraction
      after anterior myocardial infarction assessed by gated single photon emission
      computed tomography.
AB  - BACKGROUND: Even intermediate QRS prolongation without bundle branch block is
      associated with worse clinical outcome after myocardial infarction (MI). We
      assessed the association of QRS duration with left ventricular (LV) volume and
      ejection fraction after anterior MI by using quantitative gated single photon
      emission computed tomography (SPECT). METHODS: Eighty-two patients with prior
      anterior MI were enrolled. Intermediate QRS prolongation was defined as QRS
      duration >=100 ms without bundle branch block. Quantitative analysis of thallium
      SPECT was performed on the redistribution image. LV end-diastolic volume (LVEDV),
      end-systolic volume (LVESV) and ejection fraction (LVEF) were obtained. RESULTS:
      There were 25 patients with intermediate QRS prolongation and 57 patients with
      normal QRS duation. Compared to patients with normal QRS duration, patients with
      intermediate QRS prolongation had larger LVEDV (137.4 +/- 75.1 ml vs 87.9 +/-
      43.6 ml, p = .004), larger LVESV (89.9 +/- 69.6 ml vs 49.2 +/- 35.5 ml, p = .009)
      and lower LVEF (39.3 +/- 14.6% vs 47.6 +/- 12.0%, p = .02). QRS duration was
      positively associated with LVEDV (r = 0.49, p < .001) and LVESV (r = 0.47, p <
      .001), and was inversely associated with LVEF (r= -0.32, p < .001). Multivariate
      analysis showed that male sex (beta = 0.22, p = .04), QRS duration (beta = 0.34,
      p = .002) and number of abnormal Q waves (beta = 0.37, p < .001) were associated
      with LVEDV. QRS duration (beta= -0.32, p = .003) and number of abnormal Q waves
      (beta = -0.40, p < .001) were associated with LVEF. CONCLUSIONS: Our results
      suggest that QRS duration as well as number of abnormal Q waves is independently
      associated with LV volume and ejection fraction after anterior MI.

PMID- 29073827
TI  - Needlestick and Sharps Injuries Among Nursing Students in Nanjing, China.
AB  - Needlestick and sharps injuries (NSIs) are a major cause of occupational injuries
      for health care workers worldwide. In this study, the authors report the
      prevalence of and risk factors for NSIs among Chinese nursing students. A cross
      sectional survey was distributed to 442 nursing students; 393 completed
      questionnaires were submitted. A total of 237 (60.3%) nursing students reported
      NSIs, which were more commonly reported by female students, younger students,
      students who worked frequent night shifts, students without safety training, and
      students who did not use personal protective equipment. Among those injured,
      59.9% were injured by syringe needles, 21.9% by glass items, and 3.4% by
      scissors. Of those needles and sharps causing injuries, 36.3% of devices had been
      used on patients, 41% were unused, and 22.7% were unknown. Opening ampoules or
      vials was the most common injury agent. A total of 86.9% of NSIs were not
      reported to hospital infection control. Nursing students are at high risk of NSIs
      in China. Occupational safety training should be developed and implemented to
      prevent NSIs among this vulnerable population.

PMID- 29073828
TI  - Covariates of high-risk sexual behaviour of men aged 50 years and above in sub
      Saharan Africa.
AB  - Since the advent of HIV/AIDS, sexuality studies in sub-Saharan Africa (SSA) have
      focused mainly on the sexual behaviour of the younger generation (15-49 years)
      and little has been done to understand the sexual behaviour of those a 50 years
      and above. The objective of this study is therefore to examine the covariates of
      high-risk sexual behaviour among men aged 50 years plus within the SSA region.
      Data from Demographic and Health Surveys of 10 SSA countries were pooled together
      and a sample of 5394 men aged 50 years plus who have ever had sex was analysed.
      Findings show that in SSA, a large proportion of men aged 50 years plus (74%)
      were sexually active and a substantial proportion of these men engaged in unsafe
      sexual behaviours, such as having multiple sexual partners and unprotected sex.
      The multivariate logistic regression analysis showed that involvement with
      multiple sexual partners was significantly associated with older age, urban
      residence, religion, having primary or secondary education, and ever taken an HIV
      test. Condom use at last sex was significantly associated with age at first sex,
      multiple sexual partners, level of education and ever been tested for HIV. These
      results suggest that HIV prevention and intervention programmes should also
      target older men as they are also sexually active and at risk of being infected
      because of unsafe sexual practices.

PMID- 29073829
TI  - HIV testing among male partners of pregnant women in Nigeria: a missing link in
      the elimination of mother-to-child transmission of HIV.
AB  - In this study, we assessed male partner testing and the serodiscordance rate
      among pregnant women and their partners in the prevention of mother-to-child
      transmission (PMTCT) programme in Nigeria. We conducted a retrospective analysis
      of the consolidated national health sector PMTCT data over a five-year period
      (2012-2016). Over the period, a total of 11,833,062 pregnant women were tested
      for HIV with a positivity rate of 2.2%. About 266,188 (2.2%) of sexual partners
      of pregnant women who presented at PMTCT clinics had an HIV test within the
      period. The uptake of male partner testing varied across the years, ranging from
      22,269 (1.7%) in 2012 to 90,603 (2.9%) in 2014 (chi2 for trend = 1320; p <
      0.001). Overall, the proportion of partners of HIV-negative pregnant women who
      tested was higher than the proportion of partners of HIV-positive pregnant women
      (81% versus 19%, respectively). The serodiscordance rate among partners who
      tested over the five-year period was 18%. The serodiscordance rate declined from
      24% in 2012 to 13% in 2016 (chi2 for trend = 1202; p < 0.001). Partner testing in
      the PMTCT programme in Nigeria has remained low in the last five years while the
      clinic-based serodiscordance rate among partners appears to be declining. There
      is a need for multilevel interventions to address the possible barriers to
      partner testing in the PMTCT programme and intensification of the HIV combination
      prevention approach in the HIV response.

PMID- 29073830
TI  - Beneficial falls in stroke patients: evaluation using a mixed method design.
AB  - Purpose To use a mixed method design to evaluate how clinicians judge falls in
      stroke patients as a beneficial event, and to identify patient-specific
      characteristics associated with beneficial falls. Methods The definition of
      beneficial falls was based on interviews with six experienced clinicians in
      stroke rehabilitation. Interview data were analyzed using the grounded theory
      approach, with outcomes used to develop a checklist to judge falls as beneficial.
      We subsequently used the checklist to identify falls sustained by patients in our
      rehabilitation unit as beneficial events. The characteristics of beneficial
      fallers were investigated in this retrospective study. Results According to
      experienced clinicians, beneficial falls result from patient-specific factors and
      level of independence. Beneficial falls are not associated with after-effects or
      a diagnosis of cognitive impairment, do not result in physical injury and post
      fall syndrome, and do not alter the course of rehabilitation. These falls are
      considered to enhance patients' self-awareness of their physical status and
      abilities. Among the 123 stroke patients who experienced a fall in our study
      group, 23 patients (18.7%) were identified as beneficial fallers according to our
      checklist. The majority had a left hemiplegia and perceptual impairments, and
      were at low risk of recurrent falls and made functional gains during
      rehabilitation. Conclusions Based on our results, we created a 10-item checklist
      to differentiate beneficial from adverse falls. This differentiation is important
      to target fall prevention programs to adverse fallers in rehabilitation units.

PMID- 29073831
TI  - Parathyroid Hormone-Related Protein Gradients Affect the Progression of
      Mesenchymal Stem Cell Chondrogenesis and Hypertrophy.
AB  - INTRODUCTION: Mesenchymal stem cells (MSCs) are considered a promising cell
      source for cartilage repair strategies due to their chondrogenic differentiation
      potential. However, their in vitro tendency to progress toward hypertrophy limits
      their clinical use. This unfavorable result may be due to the fact that MSCs used
      in tissue engineering approaches are all at the same developmental stage, and
      have lost crucial spatial and temporal signaling cues. In this study, we sought
      to investigate the effect of a spatial parathyroid hormone-related protein
      (PTHrP) signaling gradient on the chondrogenic differentiation of MSCs and
      progression to hypertrophy. METHODS: Human bone marrow-derived MSCs were
      transduced with adenoviral vectors overexpressing PTHrP and seeded into fibrin
      poly(ester-urethane) scaffolds. To investigate the effect of a spatial PTHrP
      signaling gradient, scaffolds were seeded with PTHrP-overexpressing MSCs
      positioned on top of the scaffold, with untransduced MSCs seeded evenly within.
      Scaffolds were cultured with or without 2 ng/mL transforming growth factor (TGF)
      beta1 for 28 days. RESULTS: PTHrP overexpression increased glycosaminoglycan
      (GAG) production by MSCs irrespective of TGF-beta1 treatment, and exerted
      differential effects on chondrogenic and hypertrophic gene expression when MSCs
      were cultured in the presence of a PTHrP signaling gradient. Furthermore, PTHrP
      overexpressing MSCs were associated with an increase of endogenous TGF-beta1
      production and reduced total MMP-13 secretion compared to controls. CONCLUSION:
      The presence of a spatial PTHrP signaling gradient may support chondrogenic
      differentiation of MSCs and promote the formation of a more stable cartilage
      phenotype in tissue engineering applications.

PMID- 29073832
TI  - A Review of 20 Years of Standardization of Odor Concentration Measurement by
      Dynamic Olfactometry in Europe.

PMID- 29073833
TI  - Treatment of hypersaline hazardous landfill leachate using a baffled constructed
      wetland system: effect of granular packing media and vegetation.
AB  - Constructed wetland is an engineered system that attains more attention as a
      feasible technology for the treatment of municipal landfill leachate. However,
      its feasibility for treatment of toxic, hazardous, and hypersaline leachate
      remains unexplored. This study aimed to investigate the feasibility of using a
      baffled constructed wetland (BCW) system for the treatment of hypersaline
      hazardous landfill leachate. Furthermore, the effects of granular packing media,
      toxicity, and hyper salinity conditions on the removal efficiency of COD
      fractions (CODt, CODs, and CODp), nitrogen, heavy metals, and coarse solids were
      extensively investigated. Our findings indicated that BCWs were highly effective
      in removing heavy metals particularly Cu2+, Mn2+, Fe2+, and Zn2+ and exhibited
      moderate efficiency for other contaminants (e.g. COD fractions, solids, and
      nitrogen species). Furthermore, use of a sand and gravel mixture for bed
      materials demonstrated higher performance over sand alone. However, we found that
      Phragmites australis is not tolerant enough to extreme toxicity and salinity
      conditions, and this reed could not survive for more than 27 and 33 days in sand
      BCW and sand/gravel BCW, respectively. Consequently, survivorship of reed and
      efficiency of treatment using vegetation were limited in the long-term operation
      with high salinity and toxicity conditions.

PMID- 29073834
TI  - Theory-Based Analysis of Interest in an HIV Vaccine for Reasons Indicative of
      Risk Compensation Among African American Women.
AB  - Licensure of an HIV vaccine could reduce or eliminate HIV among vulnerable
      populations. However, vaccine effectiveness could be undermined by risk
      compensation (RC), defined by an increase in risky behavior due to a belief that
      the vaccine will confer protection. Interest in an HIV vaccine for reasons
      indicative of RC may serve as an indicator of actual RC in a postlicensure era.
      This study assessed factors associated with interest in an HIV vaccine for
      reasons indicative of RC among African American women aged 18 to 55 years,
      recruited from a hospital-based family planning clinic in Atlanta, Georgia ( N =
      321). Data were collected using audio-computer-assisted surveys. Survey items
      were guided by risk homeostasis theory and social cognitive theory. Multivariable
      logistic regression was used to assess determinants of interest in an HIV vaccine
      for reasons indicative of RC. Thirty-eight percent of the sample expressed
      interest in an HIV vaccine for at least one reason indicative of RC. In the final
      model, interest in an HIV vaccine for reasons indicative of RC was positively
      associated with higher impulsivity, perceived benefits of sexual risk behaviors,
      and perceived benefits of HIV vaccination; it was negatively associated with
      having at least some college education, positive future orientation, and self
      efficacy for sex refusal. Results suggest that demographic, personality, and
      theory-based psychosocial factors are salient to wanting an HIV vaccine for
      reasons indicative of RC, and underscore the need for risk-reduction counseling
      alongside vaccination during the eventual rollout of an HIV vaccine.

PMID- 29073835
TI  - miR-9 induces cell arrest and apoptosis of oral squamous cell carcinoma via CDK
      4/6 pathway.
AB  - Oral cancer remains a major public concern with considerable socioeconomic impact
      in the world, especially in southeast Asia. Despite substantial advancements have
      been made in treating oral cancer, the five-year survival rate for OSCC remained
      undesirable, and 35-55% patients developed recurrence within two years even with
      multimodality therapeutic strategies. Hence, identification of novel biomarkers
      for diagnosis and evaluating clinical outcome is of vital importance. MicroRNAs
      are 22-24 nt non-coding RNAs that could bind to 3' UTR of target mRNAs, thereby
      inducing degradation of mRNA or inhibiting translation. Due to its implication in
      regulation of post-transcriptional processes, the role of miRNAs in malignancies
      has been extensively studied, among which the discovery of functional miR-9 in
      oral squamous cell carcinoma (OSCC) remained to be elucidated. We first
      demonstrated that miR-9 was down-regulated in 21 OSCC patients, and we further
      found that forced expression of miR-9 could result in deterred cell proliferation
      and decreased ability to migrate and form colonies. Flow cytometry displayed cell
      cycle arrested at G0/G1 phase. We next used Targetscan to predict target genes of
      miR-9. CDK6, a protein highly implicated in cell cycle control, was chosen for
      verification. Down-regulation of CDK6 and Cyclin D1 in Tca8113 transfected with
      miR-9 mimics indicate that the complex formed by both proteins may be the
      effector of the antiproliferative function of miR-9 in OSCCs. Considering small
      molecules are developed to target CDK4/6, our finding may provide valuable
      scientific evidence for research and development of therapies and diagnostic
      methodology in OSCCs.

PMID- 29073836
TI  - Inter-rater and test-retest reliability of the Danish version of the everyday
      technology use questionnaire.
AB  - BACKGROUND: Everyday technologies are naturally integrated in people's daily
      life. For older adults and adults living with a chronic disease like chronic
      obstructive pulmonary disease (COPD), the ability to use technologies for health
      management has become increasingly important. The aim of this study was to
      investigate inter-rater and test-retest reliability of the Danish version of the
      Everyday Technology Use Questionnaire (ETUQ) in a sample of older adults with (n
      = 23) and without (n = 24) COPD. MATERIAL AND METHOD: The ETUQ was initially
      translated in accordance with the dual panel approach and then administered to a
      sample of 47 participants. Svensson's method for paired ordinal data was utilized
      to calculate and analyze reliability. RESULTS: Overall, inter-rater and test
      retest reliability of the Danish version of the ETUQ demonstrated excellent
      percentage agreement (PA) (>75%), although for test-retest reliability, nine
      items demonstrated fair (53%) to good (73%) agreement. CONCLUSION: This study
      supports the use of the Danish version of the ETUQ in a sample of older adults
      with or without COPD. Application to practice: The Danish version of the ETUQ is
      an evidence-based evaluation that can reliably contribute to clinical
      occupational therapy and research in Denmark focusing on everyday technology use.

PMID- 29073837
TI  - Rethinking the costs of psoriasis management.

PMID- 29073838
TI  - Correction to: Smith et al., Evaluation of the influence of family and friends,
      and the internet on patient perceptions of long-term topical corticosteroid use.

PMID- 29073839
TI  - Is it time that students received a foundation for research?

PMID- 29073840
TI  - A Novel Apparatus to Measure Knee Flexor Strength During Various Hamstring
      Exercises: A Reliability and Retrospective Injury Study.
AB  - Study Design Reliability and case-control injury study. Background Knee flexor
      strength is a key variable when dealing with hamstring strain injury (HSI), and
      methodologies of objective measurement of strength are often limited to single
      exercises. Objectives To establish test-retest reliability of a novel apparatus
      to measure knee flexor strength during various hamstring exercises, and to
      investigate whether the measure can detect between-leg differences in male
      participants with and without history of unilateral HSI. Methods Twenty male
      participants without and 10 male participants with previous unilateral HSI
      participated. Isometric knee flexor strength and peak rate of force development
      (RFD) at 0 degrees /0 degrees , 45 degrees /45 degrees , and 90 degrees /90
      degrees  of hip/knee flexion were measured, as well as force impulse during
      bilateral and unilateral variations of an eccentric slider and hamstring bridge,
      using a novel apparatus. Intraclass correlation coefficient (ICC), typical error,
      and typical error as a coefficient of variation were calculated for all measures.
      The magnitudes of between-leg differences within each group were calculated using
      estimates of effect sizes, reported as Cohen's d and 90% confidence interval
      (CI). Results Moderate to high test-retest reliability was observed for isometric
      knee flexor strength (ICC = 0.87-0.92) and peak RFD (ICC = 0.88-0.95) across 3
      positions and for mean force impulse during the eccentric slider (ICC = 0.83
      0.90). In those with prior HSI, large deficits were observed in the previously
      injured leg compared to the contralateral uninjured leg for mean force impulse
      during the unilateral eccentric slider (d = -1.09; 90% CI: -0.20, -1.97),
      isometric strength at 0 degrees /0 degrees  (d = -1.06; 90% CI: -0.18, -1.93) and
      45 degrees /45 degrees  (d = -0.88; 90% CI: -0.02, -1.74), and peak RFD at 45
      degrees /45 degrees  (d = -0.88; 90% CI: -0.02, -1.74). Conclusion The novel
      apparatus provides a reliable measure of isometric knee flexor strength, peak
      RFD, and force impulse during an eccentric slider, with deficits seen in
      previously injured hamstrings for these measures. J Orthop Sports Phys Ther
      2018;48(2):72-80. Epub 26 Oct 2017. doi:10.2519/jospt.2018.7634.

PMID- 29073841
TI  - Individuals Post Achilles Tendon Rupture Exhibit Asymmetrical Knee and Ankle
      Kinetics and Loading Rates During a Drop Countermovement Jump.
AB  - Study Design Cross-sectional laboratory study. Background Asymmetrical knee
      loading during jogging and hopping has been reported in individuals who have
      ruptured their Achilles tendon. No studies have examined knee loads in
      individuals post Achilles tendon rupture during high-demand tasks, such as single
      limb landings. Objectives We sought to determine whether individuals post
      Achilles tendon rupture demonstrated asymmetrical knee loads and impact forces
      during drop countermovement jumps (CMJs). Methods Achilles tendon length and the
      single-leg heel-rise test for endurance were assessed in 34 individuals (31 male)
      6.1 +/- 2.0 years post Achilles tendon rupture. Movement patterns were assessed
      during a drop CMJ. Data were analyzed via repeated-measures analyses of variance,
      with comparisons between limbs and prior treatment history (surgery versus
      nonsurgery). Results An 8.6% longer Achilles tendon (P<.001) was found in the
      involved limb. During the single-leg heel-rise test, the involved limb
      demonstrated 22.4% less endurance and 14.6% lower heel-rise height (all, P<.001).
      During the landing phase of the drop CMJ, the involved limb exhibited 39.6%
      greater loading rate (P<.001), 16.8% greater eccentric knee power (P = .048), but
      21.6% lower eccentric ankle power (P<.001). During the take-off phase, the
      involved limb exhibited 12.1% lower jump height and 19.9% lower concentric ankle
      power (both, P<.001). Conclusion Elevated eccentric knee joint power and higher
      loading rates during a drop CMJ in individuals who experienced Achilles tendon
      rupture several years earlier may be a compensation pattern for reduced plantar
      flexor function. This movement pattern may place individuals who have had an
      Achilles tendon rupture at greater risk for knee injuries. J Orthop Sports Phys
      Ther 2018;48(1):34-43. Epub 26 Oct 2017. doi:10.2519/jospt.2018.7684.

PMID- 29073842
TI  - The Influence of Patient Choice of First Provider on Costs and Outcomes: Analysis
      From a Physical Therapy Patient Registry.
AB  - Study Design Retrospective study. Background Alternative models of care that
      allow patients to choose direct access to physical therapy have shown promise in
      terms of cost reduction for neck and back pain. However, real-world exploration
      within the US health care system is notably limited. Objectives To compare total
      claims paid and patient outcomes for patients with neck and back pain who
      received physical therapy intervention via direct access versus medical referral.
      Methods Data were accessed for patients seeking care for neck or back pain (n =
      603) between 2012 and 2014, who chose to begin care either through traditional
      medical referral or direct access to a physical therapy- led spine management
      program. All patients received a standardized, pragmatic physical therapy
      approach, with patient-reported measures of pain and disability assessed before
      and after treatment. Patient demographics and outcomes data were obtained from
      the medical center patient registry and combined with total claims paid
      calculated for the year after the index claim. Linear mixed-effects modeling was
      used to analyze group differences in pain and disability, visits/time, and
      annualized costs. Results Patients who chose to enter care via the direct-access
      physical therapy-led spine management program displayed significantly lower total
      costs (mean difference, $1543; 95% confidence interval: $51, $3028; P = .04) than
      those who chose traditional medical referral. Patients in both groups showed
      clinically important improvements in pain and disability, which were similar
      between groups (P>.05). Conclusion The initial patient choice to begin care with
      a physical therapist for back or neck pain resulted in lower cost of care over
      the next year, while resulting in similar improvements in patient outcomes at
      discharge from physical therapy. These findings add to the emerging literature
      suggesting that patients' choice to access physical therapy through direct access
      may be associated with lower health care expenditures for patients with neck and
      back pain. Level of Evidence Economic and decision analyses, level 4. J Orthop
      Sports Phys Ther 2018;48(2):63-71. Epub 26 Oct 2017. doi:10.2519/jospt.2018.7423.

PMID- 29073843
TI  - Translating communication skills teaching from group-observed structured
      encounters (GOSCEs) to the ward.

PMID- 29073844
TI  - Hearing preservation cochlear implantation in children: The HEARRING Group
      consensus and practice guide.
AB  - OBJECTIVES: To provide multidisciplinary cochlear implant teams with a current
      consensus statement to support hearing preservation cochlear implantation (HPCI)
      in children, including those children with symptomatic partial deafness (PD)
      where the intention is to use electric-acoustic stimulation (EAS). The main
      objectives are to provide guidelines on who is a candidate, how to assess these
      children and when to implant if Med-El Flex electrode arrays are chosen for
      implantation. METHODS: The HEARRING group reviewed the current evidence and
      practice regarding the management of children to be considered for HPCI surgery
      emphasizing the assessment needed prior to implantation in order to demonstrate
      the benefits in these children over time. The consensus statement addresses
      following three key questions: (1) Should these children be treated? (2) How to
      identify these children? (3) How to manage these children? SUMMARY: The HEARRING
      group concludes that irrespective of the degree of residual hearing present, the
      concepts of hearing and structure preservation should be applied in every child
      undergoing cochlear implantation and that HPCI is a safe and reliable treatment
      option. Early detection and multidisciplinary assessment are key to the
      identification of children with symptomatic PD, these children should undergo
      HPCI as early as possible.

PMID- 29073845
TI  - Health-Promoting Home and Workplace Neighborhoods: Associations With Multiple
      Facets of Men's Health.
AB  - Despite the importance of healthy settings for health promotion, little is known
      about how neighborhood characteristics affect men's health. The present study
      aims to explore the associations between perceptions of home and workplace
      neighborhoods with diverse health outcomes, and to examine mediating mechanisms.
      A sample of 669 men members of labor unions in Quebec, Canada, completed a
      questionnaire assessing social and physical aspects of their work and home
      neighborhoods (the Health-Promoting Neighborhood Questionnaire) as well as
      subjective and objective health outcomes (perceived health, positive mental
      health, body mass index) and potential mediators (health behaviors, self
      efficacy). Structural equation modeling (path analysis) revealed that the Health
      Promoting Neighborhood Questionnaire was associated with all three health
      outcomes, either directly or indirectly through health behaviors and self
      efficacy. Both home and workplace neighborhoods were associated with men's
      health, home neighborhood being more strongly associated. The findings suggest
      that physical and social aspects of neighborhood might contribute to men's
      health. The study highlights positive environmental levers for urban planners,
      policy makers, and health professionals to promote men's health.

PMID- 29073846
TI  - The incidence of non-melanoma skin cancer and post-transplant lympho
      proliferative disorders in the Scottish cardiac transplant population and the
      provision of specialist dermatological follow-up.
AB  - Background Immunosuppression helps prevent acute rejection post-cardiac
      transplant but has been linked to malignancy development. This may be due to a
      reduction in T-lymphocyte function, a direct oncogenic effect or the increased
      impact of environmental carcinogens. There has been shown to be significant
      increases in non-melanoma skin cancers and post-transplant lympho-proliferative
      disorders, particularly in those treated with OKT3. Aim To investigate the
      survival and incidence of malignancy in the Scottish cardiac transplant
      population and whether rates of non-melanoma skin cancers justify the provision
      of specialist dermatological follow-up. Methods and results Retrospective case
      note analysis of patients transplanted (363) or followed up (2) in Scotland from
      1992 to 2016. Kaplan-Meier survival analysis generated a survival curve. Patients
      had a 1-year survival of 82% and a median survival of 10.9 years. There were 60
      (95% CI 47.5, 75.2) NMSCs and 8 (3.7, 12.4) post-transplant lympho-proliferative
      disorders diagnosed in the cohort (3110 person years follow-up). Fisher's exact
      test was employed to analyse the association between induction therapy (via OKT3
      or rabbit antithymocyte globulin) and post-transplant lympho-proliferative
      disorder development. Patients treated with OKT3 had a 6.7 times greater risk ( P
      = 0.014) and a shorter experience of patients treated with rabbit antithymocyte
      globulin has so far shown no significantly altered risk ( P = 1.00) of developing
      a post-transplant lympho-proliferative disorder. Conclusion Incidences of non
      melanoma skin cancers and post-transplant lympho-proliferative disorders were
      increased in the Scottish cardiac transplant population and there was a
      significant association between post-transplant lympho-proliferative disorder
      development and OKT3 therapy but not rabbit antithymocyte globulin therapy. These
      findings in Scottish patients reflect what is published in wider literature and
      support the provision of a dedicated post-transplant dermatology clinic.

PMID- 29073847
TI  - States With Medically Needy Pathways: Differences in Long-Term and Temporary
      Medicaid Entry for Low-Income Medicare Beneficiaries.
AB  - Medically needy pathways may provide temporary catastrophic coverage for low
      income Medicare beneficiaries who do not otherwise qualify for full Medicaid
      benefits. Between January 2009 and June 2010, states with medically needy
      pathways had a higher percentage of low-income beneficiaries join Medicaid than
      states without such programs (7.5% vs. 4.1%, p < .01). However, among new full
      Medicaid participants, living in a state with a medically needy pathway was
      associated with a 3.8 percentage point (adjusted 95% confidence interval [1.8,
      5.8]) increase in the probability of switching to partial Medicaid and a 4.5
      percentage point (adjusted 95% confidence interval [2.9, 6.2]) increase in the
      probability of exiting Medicaid within 12 months. The predicted risk of leaving
      Medicaid was greatest when new Medicaid participants used only hospital services,
      rather than nursing home services, in their first month of Medicaid benefits.
      Alternative strategies for protecting low-income Medicare beneficiaries' access
      to care could provide more stable coverage.

PMID- 29073848
TI  - Biodegradation of Moringa oleifera's polymer blends.
AB  - Vegetable oils are used as a base for the synthesis of polymers and monomers with
      structures similar to that of petroleum, as plasticizers for conventional
      polymers and biodegrading additives. The Moringa oleifera oil was extracted from
      seeds and polymerized after being submitted to 16 h of microwave irradiation
      without catalysers. This polymer was characterized and the efficiency of the oil
      polymerization was verified by the reduction of double bonds and the increase of
      molecular weight up to 50,000 g mol-1. Films produced by a mixture of low-density
      polyethylene (LDPE) with poly(butylene adipate-co-terephthalate)/poly(lactic
      acid) (PBAT/PLA) present low tensile resistance and low biodegradation behaviour.
      In order to improve those properties, the Moringa polymer (PMO) was mixed with
      LDPE and PBAT/PLA in specific mass concentrations. The films produced with this
      mixture were characterized and submitted to biodegradation analysis. The PMO
      behaves as a compatibilizer by improving thermal properties, reducing the
      crystalline phase and improving the biodegradation behaviour. The biodegradation
      improved up to five times in comparison to conventional polymers and it restores
      the mechanical properties.

PMID- 29073849
TI  - Temporal Variations of PM2.5, PM10, and Gaseous Precursors during the 1995
      Integrated Monitoring Study in Central California.
AB  - The spatial and temporal distributions of particle mass and its chemical
      constituents are essential for understanding the source-receptor relationships as
      well as the chemical, physical, and meteorological processes that result in
      elevated particulate concentrations in California's San Joaquin Valley (SJV).
      Fine particulate matter (PM2.5), coarse particulate matter (PM10), and aerosol
      precursor gases were sampled on a 3-hr time base at two urban (Bakersfield and
      Fresno) and two non-urban (Kern Wildlife Refuge and Chowchilla) core sites in the
      SJV during the winter of 1995-1996. Day-to-day variations of PM2.5 and PM10 and
      their chemical constituents were influenced by the synoptic-scale meteorology and
      were coherent among the four core sites. Under non-rainy conditions, similar
      diurnal variations of PM2.5 and coarse aerosol were found at the two urban sites,
      with concentrations peaking during the nighttime hours. Conversely, PM2.5 and
      coarse aerosol peaked during the morning and afternoon hours at the two non-urban
      sites. Under rainy and foggy conditions, these diurnal patterns were absent or
      greatly suppressed. In the urban areas, elevated concentrations of primary
      pollutants (e.g., organic and elemental carbons) during the late afternoon and
      nighttime hours reflected the impact from residential wood combustion and motor
      vehicle exhaust. During the daytime, these concentrations decreased as the mixed
      layer deepened. Increases of secondary nitrate and sulfate concentrations were
      found during the daylight hours as a result of photochemical reactions. At the
      non-urban sites, the same increases in secondary aerosol concentrations occurred
      during the daylight hours but with a discernable lag time. Concentrations of the
      primary pollutants also increased at the non-urban sites during the daytime.
      These observations are attributed to mixing aloft of primary aerosols and
      secondary precursor gases in urban areas followed by rapid transport aloft to non
      urban areas coupled with photochemical conversion.

PMID- 29073850
TI  - Development, Evaluation, and Application of a Primary Aerosol Model.
AB  - The Segmented-Plume Primary Aerosol Model (SPPAM) has been developed over the
      past several years. The earlier model development goals were simply to generalize
      the widely used Industrial Source Complex Short-Term (ISCST) model to simulate
      plume transport and dispersion under light wind conditions and to handle a large
      number of roadway or line sources. The goals have been expanded to include
      development of improved algorithm for effective plume transport velocity, more
      accurate and efficient line and area source dispersion algorithms, and recently,
      a more realistic and computationally efficient algorithm for plume depletion due
      to particle dry deposition. A performance evaluation of the SPPAM has been
      carried out using the 1983 PNL dual tracer experimental data. The results show
      the model predictions to be in good agreement with observations in both plume
      advection-dispersion and particulate matter (PM) depletion by dry deposition. For
      PM2.5 impact analysis, the SPPAM has been applied to the Rubidoux area of
      California. Emission sources included in the modeling analysis are: paved road
      dust, diesel vehicular exhaust, gasoline vehicular exhaust, and tire wear
      particles from a large number of roadways in Rubidoux and surrounding areas. For
      the selected modeling periods, the predicted primary PM2.5 to primary PM10
      concentration ratios for the Rubidoux sampling station are in the range of 0.39
      0.46. The organic fractions of the primary PM2.5 impacts are estimated to be at
      least 34-41%. Detailed modeling results indicate that the relatively high organic
      fractions are primarily due to the proximity of heavily traveled roadways north
      of the sampling station. The predictions are influenced by a number of factors;
      principal among them are the receptor locations relative to major roadways, the
      volume and composition of traffic on these roadways, and the prevailing
      meteorological conditions.

PMID- 29073851
TI  - Development of a PM2 5 Emissions Inventory for the South Coast Air Basin.
AB  - With the promulgation of a national PM2.5 ambient air quality standard, it is
      important that PM2.5 emissions inventories be developed as a tool for
      understanding the magnitude of potential PM2.5 violations. Current PM10
      inventories include only emissions of primary particulate matter (1 i PM),
      whereas, based on ambient measurements, both PM10 and PM2.5 emissions inventories
      will need to include sources of both 1i PM and secondary particulate matter (2i
      PM). Furthermore, the U. S. Environmental Protection Agency's (EPA) current
      edition of AP-42 includes size distribution data for 1o PM that overestimate the
      PM2.5 fraction of fugitive dust sources by at least a factor of 2 based on recent
      studies. This paper presents a PM2.5 emissions inventory developed for the South
      Coast Air Basin (SCAB) that for the first time includes both 1i PM and 2i PM. The
      former is calculated by multiplying PM10 emissions estimates by the PM2.5/PM10
      ratios for different sources. The latter is calculated from estimated emission
      rates of gas-phase aerosol precursor and gas to aerosol conversion rates
      consistent with the measured chemical composition of ambient PM2.5 concentrations
      observed in the SCAB. The major finding of this PM2.5 emissions inventory is that
      the 2i aerosol component is more than twice the 1i aerosol component, which may
      result in widely different control strategies being required for fine PM and
      coarse PM.

PMID- 29073852
TI  - Mercury Measurement and Its Control: What We Know, Have Learned, and Need to
      Further Investigate.
AB  - Based on the available evidence of health effects, the U.S. Environmental
      Protection Agency (EPA) has been evaluating the need to regulate mercury releases
      to the environment. In response to the congressional mandates in The 1990 Clean
      Air Act Amendments (CAAA), the EPA has issued the Mercury Study Report and the
      Study of Hazardous Air Pollutant Emissions from Electric Utility Steam Generating
      Units Report. In spite of the enormous effort represented by these reports, as
      well as the efforts of both the U.S. Department of Energy (DOE) and the Electric
      Power Research Institute (EPRI), in conducting the field measurement programs
      that form the basis for these reports, a definitive answer on the need for
      mercury regulation has not been found. However, the EPA, as well as other
      regulatory agencies and health researchers, have suggested a "plausible link"
      between anthropogenic sources emitting mercury and the methylation,
      bioaccumulation in the food chain, and adverse health effects in humans and
      wildlife. Policy-makers have recognized that regulations must be based on good
      science and that a number of issues still remain. These issues can generally be
      grouped into four main categories: emissions inventory, control technology, fate
      of releases, and health effects. This paper will discuss recent, ongoing, and
      planned studies to address the remaining issues regarding the presence of mercury
      in the environment, with an emphasis on those studies that are directly related
      to the DOE/Federal Energy Technology Center's (FETC) programmatic effort.

PMID- 29073853
TI  - Development of the Relationship between Odor Intensity and Threshold Dilution
      Ratio for Swine Units.
AB  - The following models of odor intensity for swine units were evaluated: the Weber
      Fechner law model, the power law model, the Stevens model, and the Beidler model.
      Data were collected from four swine rooms (farrowing, finisher, gestation, and
      nursery) and odor threshold dilution ratios were measured by a panel using a
      dynamic forced-choice olfactometer. Odor intensity scales were determined by
      eight panelists using a six-point category scale method. A nonlinear parameter
      estimation method was used to estimate the parameters in each of the models. The
      widely used Weber-Fechner law did not adequately fit the data of odor intensity
      and threshold. Both the power law and the Beidler models described the data
      effectively, but the Beidler model showed the best fit of the data and was used
      as the model to represent the relationship between odor intensity and threshold
      dilution ratio for swine buildings.

PMID- 29073854
TI  - Wintertime PM2.5 and PM10 Source Apportionment at Sacramento, California.
AB  - The chemical mass balance (CMB) model was applied to winter (November through
      January) 1991-1996 PM2.5 and PM10 data from the Sacramento 13th and T Streets
      site in order to identify the contributions from major source categories to peak
      24-hr ambient PM2.5 and PM10 levels. The average monthly PM10 monitoring data for
      the nine-year period in Sacramento County indicate that elevated concentrations
      are typical in the winter months. Concentrations on days of highest PM10 are
      dominated by the PM2.5 fraction. One factor contributing to increased PM2.5
      concentrations in the winter is meteorology (cool temperatures, low wind speeds,
      low inversion layers, and more humid conditions) that favors the formation of
      secondary nitrate and sulfate aerosols. Residential wood burning also elevates
      fine particulate concentrations in the Sacramento area. The results of the CMB
      analysis highlight three key points. First, the source apportionment results
      indicate that primary motor vehicle exhaust and wood smoke are significant
      sources of both PM2.5 and PM10 in winter. Second, nitrates, secondarily formed as
      a result of motor-vehicle and other sources of nitrogen oxide (NOx), are another
      principal cause of the high PM2.5 and PM10 levels during the winter months.
      Third, fugitive dust, whether it is resuspended soil and dust or agricultural
      tillage, is not the major contributor to peak winter PM2.5 and PM10 levels in the
      Sacramento area.

PMID- 29073855
TI  - Field Measurements of Particulate Matter Emissions, Carbon Monoxide, and Exhaust
      Opacity from Heavy-Duty Diesel Vehicles.
AB  - Diesel particulate matter (PM) is a significant contributor to ambient air PM10
      and PM2.5 particulate levels. In addition, recent literature argues that
      submicron diesel PM is a pulmonary health hazard. There is difficulty in
      attributing PM emissions to specific operating modes of a diesel engine, although
      it is acknowledged that PM production rises dramatically with load and that high
      PM emissions occur during rapid load increases on turbocharged engines. Snap
      acceleration tests generally identify PM associated with rapid transient
      operating conditions, but not with high load. To quantify the origin of PM during
      transient engine operation, continuous opacity measurements have been made using
      a Wager 650CP full flow exhaust opacity meter. Opacity measurements were taken
      while the vehicles were operated over transient driving cycles on a chassis
      dynamometer using the West Virginia University (WVU) Transportable Heavy Duty
      Vehicle Emissions Testing Laboratories. Data were gathered from Detroit Diesel,
      Cummins, Caterpillar, and Navistar heavy-duty (HD) diesel engines. Driving cycles
      used were the Central Business District (CBD) cycle, the WVU 5-Peak Truck cycle,
      the WVU 5-Mile route, and the New York City Bus (NYCB) cycle. Continuous opacity
      measurements, integrated over the entire driving cycle, were compared to total
      integrated PM mass. In addition, the truck was subjected to repeat snap
      acceleration tests, and PM was collected for a composite of these snap
      acceleration tests. Additional data were obtained from a fleet of 1996 New Flyer
      buses in Flint, MI, equipped with electronically controlled Detroit Diesel Series
      50 engines. Again, continuous opacity, regulated gaseous emissions, and PM were
      measured. The relationship between continuous carbon monoxide (CO) emissions and
      continuous opacity was noted. In identifying the level of PM emissions in
      transient diesel engine operation, it is suggested that CO emissions may prove to
      be a useful indicator and may be used to apportion total PM on a continuous basis
      over a transient cycle. The projected continuous PM data will prove valuable in
      future mobile source inventory prediction.

PMID- 29073856
TI  - Control of Fine Particulate (PM2.5) Emissions from Restaurant Operations.
AB  - This paper describes efforts to reduce particulate matter (PM) emissions from
      restaurant operations, including application of an existing control method to a
      new equipment type. Commercial charbroiling in the South Coast Air Basin results
      in emissions of approximately 10 tons/day of fine particulate matter (PM2.5) and
      1.3 tons/day of volatile organic compounds (VOCs). Over a seven-year period, the
      South Coast Air Quality Management District worked with industry to develop test
      methods for measuring emissions from various cooking operations, evaluate control
      technologies, and develop a rule to reduce these emissions. Of the two basic
      types of charbroilers-chain-driven and underfired-underfired produce four times
      the emissions when equivalent amounts of product are cooked. Cost-effective
      control technology is currently available only for chain-driven charbroilers. The
      application of flameless catalytic oxidizers to chain-driven charbroilers was
      found to effectively reduce emissions by at least 83% and is cost-effective. The
      catalysts have been used worldwide at restaurants for several years. Research
      efforts are underway to identify control options for underfired charbroilers.
      Implementation of Rule 1138, Control of Emissions from Restaurant Operations,
      adopted November 14, 1997, will result in reductions of 0.5 tons/day of PM2.5 and
      0.2 tons/day of VOCs. Future rules will result in reductions from underfired
      charbroilers and possibly other restaurant equipment when cost-effective
      solutions are available.

PMID- 29073857
TI  - Simulation of Sulfate and Nitrate Chemistry in Power Plant Plumes.
AB  - The rate of formation of secondary particulate matter (PM) in power plant plumes
      varies as the plume material mixes with the background air. Consequently, the
      rate of oxidation of sulfur dioxide (SO2) and nitrogen dioxide (NO2) to sulfate
      and nitric acid, respectively, can be very different in plumes and in the
      background air (i.e., air outside the plume). In addition, the formation of
      sulfate and nitric acid in a power plant plume is a strong function of the
      chemical composition of the background air and the prevailing meteorological
      conditions. We describe the use of a reactive plume model, the Reactive and
      Optics Model of Emissions, to simulate sulfate and nitrate formation in a power
      plant plume for a variety of background conditions. We show that SO2 and NO2
      oxidation rates are maximum in the background air for volatile organic compound
      (VOC)-limited airsheds but are maximum at some downwind distance in the plume
      when the background air is nitrogen oxide (NOx)-limited. Our analysis also shows
      that it is essential to obtain measurements of background concentrations of
      ozone, aldehydes, peroxyacetyl nitrate, and other VOCs to properly describe plume
      chemistry.

PMID- 29073858
TI  - Observations and Interpretations from the Canadian Fine Particle Monitoring
      Program.
AB  - Canadian particle monitoring programs examining PM10, PM2.5, and particle
      composition have been in operation for over 10 years. Until recently, the
      measurements were manual/filter-based with 24-hr sample collection varying in
      frequency from daily to every sixth day, using GrasebyAnderson dichotomous
      samplers. In the past few years, these monitoring activities have been expanded
      to include hourly measurements using tapered element oscillating microbalances
      (TEOMs). This continuous monitoring program started operation focusing on PM10,
      but now emphasizes PM2.5 through the addition of more TEOMs and switching of the
      inlets of some of the existing units. The data from all of these measurement
      activities show that there are broad geographical differences and also local- to
      regional-scale spatial differences in mass and composition of PM2.5. Due to
      variations in sources, significantly different PM2.5 concentrations are not
      uncommon within the same city. Comparison of nearby urban and rural sites
      indicates that 30 and 40% of the PM2.5 is from local urban sources in Montreal
      and Toronto, respectively. Hourly PM2.5 measurements in Toronto suggest that
      vehicular emissions are an important contributor to urban PM2.5. There has been a
      decreasing trend in urban PM2.5, with annual average concentrations between the
      1987-1990 and 1993-1995 periods decreasing by 11 to 39%, depending upon the site.
      The largest declines were in Montreal and Halifax, and the smallest decline was
      in Toronto. Comparison of 24-hr TEOM and manual dichotomous sampler PM2.5
      measurements from a site in Toronto indicates that the TEOM results in lower
      concentrations. The magnitude of this difference is relatively small in the
      warmer months, averaging about 12%. During the colder months the difference
      averages about 23%, but can be as large as 50%.

PMID- 29073859
TI  - Determination of PM2.5 Sulfate and Nitrate with a PC-BOSS Designed for Routine
      Sampling for Semi-Volatile Particulate Matter.
AB  - Ambient particles contain substantial quantities of material that can be lost
      from the particles during sample collection on a filter. These include ammonium
      nitrate and semi-volatile organic compounds. As a result, the concentrations of
      these species are often significantly in error for results obtained with a filter
      pack sampler. The accurate measurement of these semi-volatile fine particulate
      species is essential for a complete understanding of the possible causes of
      health effects associated with exposure to fine particles. Past organic compound
      diffusion denuder samplers developed by the authors (e.g., the Brigham Young
      University Organic Sampling System [BOSS]) are not amenable to routine field use
      because of the need to independently determine the gas-phase semi-volatile
      organic material efficiency of the denuder for each sample. This problem has been
      eliminated using a combined virtual impactor, particle-concentrator inlet to
      provide a concentrated stream of 0.1-2.5-MUm particles. This is followed by a
      BOSS diffusion denuder and filter packs to collect particles, including any semi
      volatile species lost from the particles during sampling. The samp ler (Particle
      Concentrator-Brigham Young University Organic Sampling System [PC-BOSS]) contains
      a post-denuder multifilter pack unit to allow for the routine collection of
      several sequential samples. The PC-BOSS can be used for the determination of both
      fine particulate nitrate and semi-volatile organic material without significant
      "positive" or "negative" sampling artifacts. Validation of the sampler for the
      determination of PM2.5 sulfate and nitrate based on comparison of results
      obtained at Riverside, CA with collocated PC-BOSS, annular denuder, and Chem Spec
      samplers indicates the PC-BOSS gives accurate results for these species with a
      precision of +/-5-8%. An average of 33% of the PM2.5 nitrate was lost from the
      particles during sampling for both denuder and single filter samplers.

PMID- 29073860
TI  - Designing Optimal Strategies to Attain the New U.S. Particulate Matter Standards:
      Some Initial Concepts.
AB  - This paper proposes that a fundamental principle for designing optimal strategies
      to attain new U.S. particulate matter (PM) standards be minimization of community
      and susceptible group exposure to, and inhaled dosage of, ambient PM. Properly
      done, such minimization maximizes human health risk reduction. To illustrate
      implementation of such a principle, an initial prototype model, PM Exposure
      (PMEX), is described that calculates PM exposure and inhaled dosage as figures-of
      merit for control strategy optimization. The model accounts for age-occupation
      and susceptible group activity patterns, indoor-outdoor concentration
      differences, and geographical location. Modeling results are presented for a
      hypothetical example, apportioning inhaled dosage among different classes of
      sources, under alternative assumptions about the relative potency of different PM
      species categories. The results, while preliminary, demonstrate that conclusions
      about source class contribution based on inhaled dosage can be appreciably
      different than those based on ambient air measurements or emission inventories.

PMID- 29073861
TI  - The Effects of Chloride Additives on Adsorption of Heavy Metals during
      Incineration.
AB  - The dynamic adsorption behaviors and characteristics of heavy metals on a sorbent
      at different temperatures have been investigated in a previous study by the same
      authors. The present work focuses on the dynamic adsorption behaviors of Cr, Cu,
      Pb, and Cd on a sorbent (silica sand with limestone) under various chloride
      additive conditions (no chloride; an organic chloride, polyvinyl chloride [PVC];
      and an inorganic chloride, sodium chloride [NaCl]), and estimates the adsorption
      saturation point of the sorbent during fluid-ized-bed incineration. The results
      will enable us to evaluate the effects of various chloride additives on the
      adsorption efficiency of heavy metals and to determine when the sor-bents should
      be renewed. From the perspective of controlling heavy metal emissions, the
      results indicated that (1) using the NaCl additive generally led to a higher
      adsorption capacity than did a PVC additive or no additive at all; and (2)
      cadmium was extremely difficult to remove in any situation. Most adsorption
      curves of chloride additives did not reach the adsorption saturation point
      because of their relatively high volatility. Under the same chloride additives
      condition, the adsorption capacities of the sorbent for the four metals followed
      the sequence Pb>Cu>Cr>Cd with no chloride additive; Cr>Pb>Cu>Cd with PVC
      additives; and Cu>Cr>Pb>Cd with NaCl additives.

PMID- 29073862
TI  - Spatial Factors Influencing Winter Primary Particle Sampling and Interpretation.
AB  - Aerosol samplers collect material that is locally generated as well as that
      transported from upwind; knowing the extent of the area from which the sample is
      drawn is necessary for proper interpretation of sampler data. The U.S.
      Environmental Protection Agency (EPA) PM2.5 monitoring guidelines recognize a
      conceptual hierarchy of sampler spatial representation, but provide no objective
      measures of a site's spatial representativeness. A case study of a sampler
      tributary area in central California provides insights into the factors that
      determine a sampler's spatial representation. Winter diurnal cycles of fine
      particle concentrations at places of habitation ranging from urban cores to small
      farm towns show a marked cycle that can be linked to local human activity.
      Assessment of the possible causes of the observed cycles leads to the hypothesis
      that local sources dominate primary particle mass in winter samples. The
      hypothesis was tested using a simple model to relate routine 24-hr PM10 and PM2.5
      samples to a sampler's surroundings. Model results indicate that even minor
      sources very close to a sampler will overwhelm any regional component in a
      sample. The results for the cases studied also demonstrate that, in winter, most
      coarse (PM10-2.5) particles collected are less than 2 hr old, and most primary
      fine (PM2.5) particles are less than 4 hr old. Even on days that are not truly
      "stagnant," samplers are very strongly influenced by their immediate surroundings
      (distances less than 10 km), and only weakly influenced by regional emissions.
      The implications for interpretation of sample analyses are as follows: 1. Typical
      PM sampling networks are unlikely to represent regional conditions; 2. Similarity
      of samples in time and space between widely separated samplers probably arises
      from sampling analogous local environments rather than a uniformly mixed regional
      air mass; 3. Even weak sources near a sampler will prevent regionally
      representative samples, so that "background" specification in models can be
      strongly skewed by misapplication of sampler data; 4. Source-receptor
      relationships within a single modeling grid cell can cause measured and modeled
      source impacts at a sampler to diverge by orders of magnitude, even for grid
      cells as small as 1 km; and 5. Differential deposition of coarse and fine
      particles will skew source apportionment by chemical tracers unless the tracers
      and the source emissions have the same size distribution.

PMID- 29073863
TI  - Comparison of Analytical Techniques for Measuring Hydrocarbon Emissions from the
      Manufacture of Fiberglass-Reinforced Plastics.
AB  - Research Triangle Institute and the U.S. Environmental Protection Agency
      conducted several projects to measure hydrocarbon emissions associated with the
      manufacture of fiberglass-reinforced plastics. The purpose of these projects was
      to evaluate pollution prevention techniques to reduce emissions by altering raw
      materials, application equipment, and operator technique. Analytical techniques
      were developed to reduce the cost of these emission measurements. Emissions from
      a small test mold in a temporary total enclosure (TTE) correlated with emissions
      from full-size production molds in a separate TTE. Gravimetric mass balance
      measurements inside the TTE generally agreed to within +/- 30 % with total
      hydrocarbon (THC) measurements in the TTE exhaust duct. Pure styrene evaporation
      tests served as quality control checks for THC measurements and generally agreed
      to within +/- 5 %.

PMID- 29073864
TI  - Representative Sampling of High-Level Radioactive Waste Tank Headspaces.
AB  - Headspaces of the underground high-level radioactive waste-storage tanks at the
      U.S. Department of Energy's Hanford Site have been sampled to resolve tank safety
      and industrial hygiene issues and to estimate regulated air pollutant emissions.
      Because sampling these tanks is difficult and expensive, samples have been
      collected from a single location of the headspaces, based on the supposition that
      this would provide representative samples. In most tanks, mixing of vapors occurs
      because of thermally driven convection from heat generated by radioactive decay
      of the waste. However, in some low-temperature tanks, the ground temperature
      above the tank may be warmer than the waste, minimizing thermally induced
      convection, and raising the concern that samples from a single location may not
      be representative. To resolve this issue, six samples at different vertical and
      horizontal locations were taken from each of three low-temperature tanks and
      analyzed for ammonia, water, permanent gases, total non-methane organic compound
      concentration, and selected organic vapors. Statistical analysis of the data
      indicated that the tanks did not exhibit significant horizontal or vertical
      concentration gradients.

PMID- 29073865
TI  - Nitrate Artifacts during PM25 Sampling in the South Coast Air Basin of
      California.
AB  - In February 1993, the South Coast Air Basin (SCAB) was redesignated as a
      "serious" nonattainment area for PM10. To improve the understanding and
      characterization of fine particulate matter in the SCAB, the South Coast Air
      Quality Management District (SCAQMD) initiated a comprehensive PM10 Technical
      Enhancement Program (PTEP). Using enhanced PTEP monitors (specially designed
      multichannel/multifilter samplers), a one-year fine particulate matter (PM)
      monitoring program was initiated in January 1995. As part of the special
      monitoring program, nitric acid, ammonia, and speciated PM10 and PM2.5
      concentrations were measured at five locations in the SCAB (downtown Los Angeles,
      Anaheim, Diamond Bar, Fontana, and Rubidoux) and at one background station (San
      Nicolas Island). The PM2.5 data are the first spatially resolved speciated data
      collected in the SCAB on an annual basis. Within the SCAB, where nitrate is a
      major component of PM2.5, nitrate losses have been documented. The spatial and
      temporal variations of the nitrate losses during PM2.5 sampling and the
      uncertainties of the nitrate losses are discussed. Significant losses occur at a
      low mass range, between 10 and 50 ig/m3. Significant gains occur at an even lower
      mass range of less than 30 ig/m3. On an annual average basis, nitrate losses vary
      between 1.25 and 2.32 ig/m3 and the SCAB-wide average value of nitrate loss is
      1.8 ig/m3 based on five PTEP stations in the SCAB. The maximum nitrate losses for
      each station vary from 6.4 ig/m3 to 22.5 ig/m 3. Theoretical prediction of the
      sampling efficiency of the nitrate during PM2.5 sam - pling was compared with the
      PTEP data. In general, theoretical prediction was in good agreement with measured
      values.

PMID- 29073866
TI  - Welcome to a Special Issue on PM25: A Fine Particle Standard.

PMID- 29073867
TI  - An Evaluation of Municipal Solid Waste Composition Bias Sources.
AB  - The University of Central Florida (UCF) was contracted by the Florida Center for
      Solid and Hazardous Waste Management (FCSHWM) to develop a well-defined
      methodology for conducting municipal solid waste composition studies. This
      methodology must account for the statistical variations in waste composition, be
      economical and practical in implementation, and build on a consensus of waste
      management professionals. This paper identifies possible sources of bias in waste
      composition study results and provides guidance for future planning of local
      waste stream composition analysis. To accomplish this objective, a composition
      study was designed and implemented for Marion County, FL, in fall 1996. The
      potential sources of concern investigated in detail were sample weight and
      contamination. The methodology developed by UCF is statistically valid and if
      widely implemented would provide a better representation of the waste stream.
      Lack of contamination adjustment is a major contributor to error in the waste
      stream analysis and should be accounted for in the methodology. For sample sorts
      using a large number of categories, sample size may be a contributor to bias.
      This likelihood for bias can be reduced by increasing the sample weight to at
      least200 kg, particularly when sorting commercial loads or reducing the number of
      categories.

PMID- 29073868
TI  - PM Emissions Emanating from Limited-Access Highways.
AB  - Motor vehicle contributions to primary particulate matter (PM) emissions include
      exhaust, tire wear, brake and clutch wear, and resuspended road dust. Relatively
      few field studies have been conducted to quantify fleetaverage exhaust emissions
      for actual on-road conditions. Therefore, direct measurements of motor vehicle
      related PM emissions are warranted. In this study, PM10 and PM2.5 mass
      concentrations were measured near two major highways in the St. Louis area over
      the period from February-April 1997. Samplers were deployed both upwind and
      downwind of the roadways to capture the transport and dispersion of PM with
      distance from the roadway. The observed microscale concentration fields were
      compared to estimates using the PART5 emission factor model together with the
      CALINE4 highway dispersion model. Traffic- induced PM mass concentrations
      observed downwind of the roadway were always less than PART5/CALINE4 predictions;
      average percent differences for observed traffic-induced mass concentrations
      compared to predicted values were -34% for PM2.5 and -70% for PM10. In most
      cases, the observed PM concentration decay with increasing distance from the
      roadway was steeper than predicted by dispersion modeling. Motor vehicle-induced
      emission factors were reconstructed by fitting CALINE4 to the observed
      concentration data with the emission factor as the sole adjustable parameter.
      Reconstructed fleet-average motor vehicle emission factors for the urban
      interstate highway were 0.03-0.04 g/VMT for both PM2.5 and PM10, while the fleet
      average emission factors for the rural interstate highway were 0.2 and 0.3 g/VMT
      for PM2.5 and PM10, respectively.

PMID- 29073869
TI  - Techniques for High-Quality Ambient Coarse Particle Mass Measurements.
AB  - Several recent studies have shown associations between ambient concentrations of
      particle mass (PM) and rates of morbidity and mortality in the general
      population. These studies have raised the issue of quality of coarse mass (CM, PM
      between 2.5 and 10 um) data used for these purposes. CM data may have precision
      three or more times worse than the associated PM 2.5 or PM10 data, depending on
      the measurement method, PM 2.5 to PM 10 ratios, and CM concentrations. CM is
      measured either as the difference between collocated PM10 and PM2.5 samplers or
      more directly with a dichotomous (virtual impactor) sampler. CM precision for the
      difference method is degraded due to the increased errors inherent with using the
      difference between two independent measurements, as well as the high PM2.5 to
      PM10 ratios (and low CM concentrations) typical of the eastern United States. The
      dichotomous sampler (dichot) makes a more direct measurement of CM, but there is
      a potential for significant postexposure loss of particles from unoiled CM dichot
      filters, as well as uncertainties in the dichot's CM channel enrichment factor.
      Compared to the dichot, low-volume inertial impactor samplers such as the Harvard
      Impactor (HI) or PM2.5 Federal Reference Method (FRM) are simpler to operate and
      maintain, provide sharper cut points, and do not require oiled filters to prevent
      loss of CM from the filter during transport. With the recent interest in CM
      spatial and temporal variability with respect to PM health effects, we have
      developed modifications to the HI PM method to provide measurements of 24-hour PM
      with estimated CM precision of better than 5% CV and r2 higher than 0.95,
      primarily by lowering field blank variability and increasing gravimetric
      analytical precision. These high-precision PM techniques are not limited to the
      HI sampler; they can also be applied to the PM2.5 FRM sampler. The measurement
      methods described here can be applied to future PM studies to avoid the potential
      problems with exposure assessment caused by CM measurements that have poor
      precision.

PMID- 29073870
TI  - An Integrated Modeling System for the Estimation of Motor Vehicle Emissions.
AB  - The paper provides a summary of accomplished and ongoing activities in the field
      of motor vehicle emission modeling in Europe. These activities have led to the
      development of a system of methods and conesponding computer models that address
      all the issues related to motor vehicle emissions that are of interest to policy
      makers, institutions, and the automotive and oil industries. The Coordination of
      Information on Air Emissions/Computer Program to Calculate Emissions from Road
      Traffic (CORLNAIR/COPERT) methodology for the estimation of emissions from road
      vehicles is presented and compared with other models. A COPERT-based approach for
      microscale traffic emission estimation, with direct application in regional and
      urban emission inventories, is outlined, and relevant case studies are briefly
      discussed. The FOREMOVE model, developed for forecasts of motor vehicle
      emissions, is presented, together with some results from its application in the
      European Auto/Oil program. Particular attention is given to modeling the
      deterioration of in-use vehicles. Finally, the major areas of further research in
      the field of vehicle emissions in Europe are indicated.

PMID- 29073871
TI  - Objectives and Design of Central California's 1995 Integrated Monitoring Study of
      the California Regional PM10/PM2.5 Air Quality Study.
AB  - The 1995 Integrated Monitoring Study (IMS95) is part of the Phase 1 planning
      efforts for the California Regional PM10/PM2.5 Air Quality Study. Thus, the
      overall objectives of IMS95 are to (1) fill information gaps needed for planning
      an effective field program later this decade; (2) develop an improved conceptual
      model for pollution buildup (PM10, PM2.5, and aerosol precursors) in the San
      Joaquin Valley; (3) develop a uniform air quality, meteorological, and emissions
      database that can be used to perform initial evaluations of aerosol and fog air
      quality models; and (4) provide early products that can be used to help with the
      development of State Implementation Plans for PM10. Consideration of the new
      particulate matter standards were also included in the planning and design of
      IMS95, although they were proposed standards when IMS95 was in the planning
      process.

PMID- 29073873
TI  - The Impact of Particulate Matter on Daily Mortality in Bangkok, Thailand.
AB  - Several studies conducted in U.S. cities report an association between acute
      exposures to particulate matter (PM), usually measured as PM10, and mortality.
      Evidence of high concentrations of PM10 in Eastern Europe and in large
      metropolitan areas outside of the United States, such as Mexico City and Bangkok,
      underscores the need to determine whether these same associations occur outside
      of the United States. In addition, conducting studies of mortality and air
      pollution in regions that have distinctly different seasonal patterns than those
      of the United States provides an effective opportunity to assess the potentially
      confounding aspects of seasonality. Over the last few years, daily measures of
      ambient PM10 have been collected in Bangkok, a tropical city of over 6 million
      people. In this metropolitan area, PM10 consists largely of fine particles
      generated from diesel- and gasoline-powered automobiles, and from two-stroke
      motorcycle engines. Our analysis involved the examination of the relationship
      between PM10 and daily mortality for 1992 through 1995. In addition to counts of
      daily natural mortality (total mortality net of accidents, homicides, and
      suicides), the data were compiled to assess both cardiovascular and respiratory
      mortality, and natural mortality by age group. A multivariate Poisson regression
      model was used to explain daily mortality while controlling for several
      covariates including temperature, humidity, day of the week, season, and time.
      The analysis indicated a statistically significant association between PM10 and
      all of the alternative measures of mortality. The results suggest a 10-ug/m3
      change in daily PM10 is associated with a 1-2% increase in natural mortality, a 1
      2% increase in cardiovascular mortality, and a 3-6% increase in respiratory
      mortality. These relative risks are generally consistent with or greater than
      those reported in most studies undertaken in the United States.

PMID- 29073875
TI  - Multi-Market Impacts of Market-Based Recycling Initiatives.
AB  - In 1995 the average tipping fee in the state of New York was $70/ton, with some
      landfills charging as high as $100.1 In New Jersey, fees reached prices as high
      as $165/ton.2 With budget crises occurring at all levels of government,
      economists, environmental scientists, policy-makers, and others are scrambling to
      find alternatives to waste disposal. Recycling as a solution has risen to the
      forefront, most likely because it both saves landfill space and may use fewer
      resources than virgin material processing. At every level of government, policies
      are being set that encourage recycling. Unfortunately, some of these programs may
      be resulting in unintended and undesirable side effects. To understand these
      effects, a broader view of the many factors involved in materials use, waste
      generation, and disposal is necessary. Within this paper, the broader view is
      considered, including a discussion of the externalities that exist in the markets
      affected by waste and an analysis of the effects on all alternatives to
      recycling, including composting and reuse. Through use of mathematical
      optimization, this paper shows that a recycling subsidy, or the more complicated
      tax/subsidy scheme, does not necessarily provide greater environmental benefits
      compared with disposal taxes.

PMID- 29073876
TI  - PM Fine Standards and Implied Modeling/Analysis Needs.
AB  - New National Ambient Air Quality Standards (NAAQS) were promulgated for fine
      particulate matter (FPM) in July 1997. This paper summarizes likely timing for
      implementing programs to meet these standards, which have a bearing on future
      modeling/analysis needs. The paper notes technical requirements implied by the
      nature of the NAAQS, as well as feedback the agency has received concerning
      modeling/analysis through Federal Advisory Committee Act (FACA) subcommittee work
      groups. Conclusions and recommendations drawn from recently completed U.S.
      Environmental Protection Agency (EPA)- sponsored workshops on modeling and other
      source attribution techniques are also described. Efforts to respond to needs
      implied by the NAAQS and feedback are noted by outlining major topics and issues
      that future guidance on use of modeling and other analyses used for attainment
      demonstrations will need to address. The paper concludes by highlighting several
      as yet unmet modeling/analysis needs to support a well-founded strategy for
      meeting air quality goals for FPM. These are suggested as potential areas for
      policy-relevant research.

PMID- 29073877
TI  - A Qualitative Approach to Evaluating the Anticipated Reliability of a
      Photochemical Air Quality Simulation Model for a Selected Application.
AB  - Photochemical air quality simulation models are now used widely in evaluating the
      merits of alternative emissions control strategies on spatial scales from
      metropolitan to sub-continental. Greatly varying levels of resources have been
      available to support modeling, from relatively comprehensive databases and
      evaluation of performance to a paucity of aerometric data for developing model
      inputs. Where data are sparse, many alternative outcomes are consistent with the
      knowledge at hand. Where performance evaluation is inadequately supported, the
      probability of error may be high. In each instance, uncertainties may be large
      when compared with the signal of interest, and thus confidence in the reliability
      of the model as an estimator of future air quality may come into question. This
      paper proposes a qualitative procedure for assessing whether a particular
      application of a modeling system is likely to be potentially unreliable,
      suggesting that either (1) modification and further evaluation is needed, if
      supportable, prior to adoption for regulatory application; or (2) the model
      should not be used if improvement is not supportable. The procedure is proposed
      for use by policy-makers, staffs of public agencies, air quality managers,
      environmental staffs of industrial organizations, and other interested parties.
      The proposed use of the procedure is (1) to assess, a priori, whether a proposed
      application is likely to be judged questionable or unacceptably uncertain in
      outcome; and (2) to provide, a posteriori, a basis for judging quickly the likely
      quality of model performance. The procedure is presented with tropospheric ozone
      as the pollutant of concern. With adjustments, however, the procedure should be
      applicable for particu-late matter and other pollutants of interest.

PMID- 29073878
TI  - Light-Duty Motor Vehicle Exhaust Particulate Matter Measurement in the Denver,
      Colorado, Area.
AB  - A study of particulate matter (PM) emissions from in-use, light-duty vehicles was
      conducted during the summer of 1996 and the winter of 1997 in the Denver, CO,
      region. Vehicles were tested as received on chassis dynamometers on the Federal
      Test Procedure Urban Dynamometer Driving Schedule (UDDS) and the IM240 driving
      schedule. Both PM10 and regulated emissions were measured for each phase of the
      UDDS. For the summer portion of the study, 92 gasoline vehicles, 10 diesel
      vehicles, and 9 gasoline vehicles with visible smoke emissions were tested once.
      For the winter, 56 gasoline vehicles, 12 diesel vehicles, and 15 gasoline
      vehicles with visible smoke were tested twice, once indoors at 60  degrees F and
      once outdoors at the prevailing temperature. Vehicle model year ranged from 1966
      to 1996. Impactor particle size distributions were obtained on a subset of
      vehicles. Continuous estimates of the particle number emissions were obtained
      with an electrical aerosol analyzer. This data set is being provided to the
      Northern Front Range Air Quality Study program and to the State of Colorado and
      the U.S. Environmental Protection Agency for use in updating emissions
      inventories.

PMID- 29073881
TI  - Evaluation of Chemical Compatibility Testing of Geomembranes Using the
      Comprehensive Test System and EPA Method 9090.
AB  - Tests of the compatibility of geomembrane (GM) samples with waste were conducted
      using U.S. Environmental Protection Agency (EPA) Method 9090 and the
      Comprehensive Testing System (CTS). The CTS is a multi-axial performance test
      capable of simultaneous cyclic mechanical loads and chemical exposure. The test
      chemicals consisted of solvents, transportation-related compounds, and
      synthesized landfill leachate. Method 9090 testing was unable to distinguish
      between the effects of individual chemicals to which the GM was subjected, while
      the CTS was able to provide statistically-significant differences that were also
      traceable to chemical properties of the solvent and the GM liner. Further, the
      time required for changes in mechanical properties of the GM was significantly
      shorter than would be expected based upon diffusion of the solvent into the GM
      alone. The combination of chemical attack with mechanical load was found to
      enhance both reduction in mechanical properties and the ability of the solvent to
      diffuse into the GM. The CTS is a more realistic test than the existing standard
      test methods because of its ability to provide multi-axial loads and chemical
      exposure simultaneously.

PMID- 29073879
TI  - Historic PM2.5/PM10 Concentrations in the Southeastern United States-Potential
      Implications of the Revised Particulate Matter Standard.
AB  - This report summarizes a PM2.5/PM10 particulate matter data set consisting of 861
      PM2.5/PM10 sample pairs collected with dichotomous samplers by the Tennessee
      Valley Authority (TVA) from 1982 to 1991. Eight monitoring stations, ranging from
      urban-industrial to rural-background, were operated across three east-central
      U.S. states. Annual average PM2.5 concentrations ranged from 12.6 to 21.3
      micrograms per cubic meter (MUg/m3), with an overall mean of 15.7 MUg/m3.
      Likewise, annual average PM10 concentrations ranged from 17.8 to 33.7 MUg/m3,
      with an overall mean of 23.7 MUg/m3. High summer-low winter seasonality was
      evident, particularly for PM2.5, with the highest monthly PM2.5 and PM10
      concentrations in August (26.4 and 37.5 MUg/m3, respectively) and the lowest in
      February (9.9 and 15.3 MUg/m3, respectively). A strong association (r2 = 0.84)
      was found between PM and PM mass with PM mass contributing, on average, 67% of
      PM10 mass. Applying TVA's PM2 5/PM10 ratio to recent (1993-1995) regional high
      volume PM10 Aerometric Information Retrieval System (AIRS) data for the east
      central United States suggests that as many as 80% of monitored counties would
      have equaled or exceeded the level of the new annual PM2.5 metric of 15 MUg/m3. A
      decline in average PM2.5 mass on the order of 3-5 MUg/m3 from 1982 through 1991
      is also suggested. Daily PM2 5 mass appears to be reasonably well associated (r =
      0.47) with maximum hourly ozone during the warmer months (spring through fall).
      Sulfate compounds comprise a major portion of the measured PM2 5 mass, with that
      fraction being highest in the summer months. Viewed collectively, these data
      suggest that although compliance with the annual and 24-hr PM and 24-hr PM
      metrics should prove readily attainable, the annual PM2.5 metric will present a
      major regulatory management challenge for much of the east-central United States.

PMID- 29073882
TI  - Maximizing Data Quality in the Gravimetric Analysis of Personal Exposure Sample
      Filters.
AB  - The weighing of particle sampler filters has always been plagued by problems in
      the weighing environment: humidity, temperature, drafts, vibration, and
      electrostatic charges on the filters. These are particularly critical for samples
      with small mass collections, such as those encountered in personal exposure
      monitoring for PM25. While modern electronic balances offer substantial
      reductions in the effects of temperature and vibration, these balances are still
      sensitive to factors such as thermal drafts and zero shifts from tilting. Drafts
      may be controlled through room ventilation modifications, and zero drift can be
      eliminated by computer-assisted data collection algorithms. A less well
      understood influence is static charge, which is often controlled with a simple
      radioactive neutralizer. Although radioactive neutralizes are effective, their
      effectiveness decays rapidly with time, and their use may be objectionable for
      nontechnical reasons. We have analyzed a number of environmental factors
      influencing gravimetric microbalance operations and have developed methods to
      minimize or eliminate them.

PMID- 29073883
TI  - Characterization of Particulate Matter in California.
AB  - The size, composition, and concentration of particulate matter (PM) vary with
      location and time. Several monitoring/sampling programs are operated in
      California to characterize PM less than 2.5 and 10 um in aerodynamic diameter
      (PM2.5 and PM10). This paper presents a broad summary of the spatial and temporal
      variations observed in ambient PM2.5 and PM10 concentrations in California. Many
      areas that have high PM10 concentrations also have relatively high PM2.5
      concentrations, and data indicate that a significant portion of the PM10 air
      quality problem is caused by PM2.5. To develop effective plans for attaining the
      ambient PM standards, improved understanding of these unique problems is needed.
      Since 1989, pollution control efforts-whether specifically targeted for
      particulate matter or indirectly via controls on gaseous emissions-have caused
      annual average PM2.5 and PM10 concentrations to decline at most sites in
      California.

PMID- 29073884
TI  - Vapor Pressure Measurement System for Heavy Crude Oils.
AB  - We describe a new, simple apparatus that permits accurate measurement of reactive
      organic carbon vapor pressure from heavy crude oils when used with a gas chro
      matograph. The apparatus is analogous to the Reid vapor pressure apparatus that
      is used for vapor pressure measurement of light hydrocarbons. This system
      overcomes many of the shortcomings experienced when the Reid method is applied to
      heavy crudes. We explain the operation of the system and present results from
      measurement of heavy crudes from Southern California. Measurements on oil samples
      collected from storage tanks agreed well with analysis of headspace gases in the
      tanks.

PMID- 29073885
TI  - Cognitive impairment and hypertension in older adults living in extreme poverty:
      a cross-sectional study in Peru.
AB  - BACKGROUND: Previous studies have shown that hypertension is a risk factor for
      cognitive impairment, but whether this association is also present in extremely
      poor populations in Low Middle Income Countries settings remains to be studied.
      Understanding other drivers of cognitive impairment in this unique population
      also merits attention. METHODS: We performed a secondary analysis using data from
      the "Encuesta de Salud y Bienestar del Adulto Mayor", a regional survey conducted
      in an extremely poor population of people older than 65 years old from 12
      Peruvian cities in 2012. The outcome variable was cognitive impairment,
      determined by a score of <=7 in the modified Mini-Mental State Examination. The
      exposure was self-reported hypertension status. Variables such as age, gender,
      controlled hypertension, education level, occupation, depression and area of
      living (rural/urban) were included in the adjusted analysis. We used Poisson
      regression with robust variance to calculate prevalence ratios (PR) and 95%
      confidence interval (95% CI) adjusting for confounders. RESULTS: Data from 3842
      participants was analyzed, 51.8% were older than 70 years, and 45.6% were
      females. The prevalence of cognitive impairment was 1.7% (95% CI 1.3%-2.1%).
      There was no significant difference on the prevalence of cognitive impairment
      between the group of individuals with hypertension in comparison with those
      without hypertension (PR = 0.64, 95% CI 0.33-1.23). CONCLUSIONS: The association
      described between hypertension and cognitive impairment was not found in a sample
      of extremely poor Peruvian older adults.

PMID- 29073886
TI  - Ultra high-field SWI of the substantia nigra at 7T: reliability and consistency
      of the swallow-tail sign.
AB  - BACKGROUND: The loss of the swallow-tail sign of the substantia nigra has been
      proposed for diagnosis of Parkinson's disease. Aim was to evaluate, if the sign
      occurs consistently in healthy subjects and if it can be reliably detected with
      high-resolution 7T susceptibility weighted imaging (SWI). METHODS: Thirteen
      healthy adults received SWI at 7T. 3 neuroradiologists, who were blinded to
      patients' diagnosis, independently classified subjects regarding the swallow-tail
      sign to be present or absent. Accuracy, positive and negative predictive values
      (PPV and NPV) as well as inter- and intra-rater reliability and internal
      consistency were analyzed. RESULTS: The sign could be detected in 81% of the
      cases in consensus reading. Accuracy to detect the sign compared to the consensus
      was 100, 77 and 96% for the three readers with PPV reader 1/2/3 = 1/0.45/0.83 and
      NPV = 1/1/1. Inter-rater reliability was excellent (inter-class correlation
      coefficient = 0.844, alpha = 0.871). Intra-rater reliability was good to
      excellent (reader 1 R/L = 0.625/0.786; reader 2 = 0.7/0.64; reader 3 = 0.9/1).
      CONCLUSION: The swallow-tail sign can be reliably detected. However, our data
      suggest its occurrence is not consistent in healthy subjects. It may be possible
      that one reason is an individually variable molecular organization of nigrosome 1
      so that it does not return a uniform signal in SWI.

PMID- 29073887
TI  - Effects of Osteoglycin (OGN) on treating senile osteoporosis by regulating MSCs.
AB  - BACKGROUND: Significant amount of bone mass is lost during the process of aging
      due to an imbalance between osteoblast-mediated bone formation and osteoclast
      mediated bone resorption in bone marrow microenvironment, which leads to net bone
      loss in the aging population, resulting in the pathogenesis of osteoporosis.
      METHODS: Firstly, differences in proliferative capacity of adipocyte or
      adipogenic differentiation in mouse mesenchymal stem cells (MMSCs) and senile
      mouse model-derived bone marrow mesenchymal stem cells (SMMSCs), as well as mRNA
      expression of OGN and PPARgamma2 were observed. Secondly, osteogenic abilities of
      MMSCs and SMMSCs treated with rosiglitazone (a PPARgamma2 agonist) to induce
      osteogenic changes were observed, and negative correlation of PPARgamma2 with OGN
      was evaluated. Thirdly, the role of SMMSCs in promoting osteogenesis was examined
      through enhancing expression of OGN; besides, the related mechanism was
      investigated by means of expression of related adipocyte and osteoblast specific
      genes. RESULTS: Forced OGN expression by OGN-infected lentivirus could increase
      expression of Wnt5b, RUNX2, OCN, ALP and Colla1, as well as bone formation, while
      decreases expression of adipogenesis marker PPARgamma2. It resulted in expression
      inhibition of adipocyte genes such as adipocytic differentiation related genes
      adipocyte binding protein 2 (aP2) and osteoclast differentiation factor Rankl in
      bone marrow, giving rise to increased bone mass. CONCLUSION: OGN may plays a
      significant role in osteoporosis, which may also provide a potential target for
      therapeutic intervention of senile osteoporosis characterized by altered
      differentiation of BMSCs into osteoblasts and adipocytes.

PMID- 29073888
TI  - Effective and rapid treatment of wound botulism, a case report.
AB  - BACKGROUND: The latest news shows several cases of contaminated heroin that is
      found in different parts all over Europe. This information can be helpful for the
      emergency doctors to find the correct diagnosis of wound botulism in patients who
      are intravenous drug users. CASE PRESENTATION: We describe a case of a 40-year
      old man who presented to the emergency department in 2016. He suffered from mild
      dysarthria, diplopia, dysphagia and ptosis since two days. The CT-scan of the
      cerebrum and the liquor were without any pathological results. We found out that
      the patient is an intravenous drug user and the clinical examination showed an
      abscess in the left groin. So we treated him with the suspected diagnosis of
      wound botulism. In the emergency operation we split the abscess, made a radical
      debridement and complementary treated him with a high dose of penicillin g and
      two units of botulism antitoxin. The suspected diagnosis was confirmed a few days
      later by finding the Toxin B in the abscess and in the patient's serum. In the
      following days the neurological symptoms decreased and the wound healing was
      without any complications. The patient left the hospital after nine days; the
      antibiotic therapy with penicillin g was continued for several days. In a
      following examination, 14 days after the patient's discharge of the hospital, no
      further symptoms were found and the abscess was treated successfully without any
      problems. CONCLUSION: Because wound botulism is a very rare disease it can be
      challenging to the attending physician. This case shows a fast treatment with
      full recovery of the patient without any further disabilities, which can be used
      for the future.

PMID- 29073889
TI  - Intra- versus retroplacental hematomas: a retrospective case-control study on
      pregnancy outcomes.
AB  - BACKGROUND: Intrauterine hematomas are a common pregnancy complication. The
      literature lacks studies about outcomes based on hematoma localization. Thus, we
      aimed to compare pregnancies complicated by an intraplacental hematoma to cases
      with a retroplacental hematoma and to a control group. METHODS: In a
      retrospective case-control study, 32 women with an intraplacental hematoma, 199
      women with a retroplacental hematoma, and a control group consisting of 113 age
      matched women with no signs of placental abnormalities were included. Main
      outcome measures were pregnancy complications. RESULTS: Second-trimester
      miscarriage was most common in the intraplacental hematoma group (9.4%), followed
      by women with a retroplacental hematoma (4.2%), and controls (0%; p = 0.007). The
      intraplacental hematoma group revealed the highest rates for placental
      insufficiency, intrauterine growth retardation, premature preterm rupture of
      membranes, preterm labor, preterm delivery <37 weeks, and early preterm delivery
      <34 weeks (p < 0.05), followed by the retroplacental hematoma group. When tested
      in multivariate models, intraplacental hematomas were independent predictors for
      placental insufficiency (beta = 4.19, p < 0.001) and intrauterine growth
      restriction (beta = 1.44, p = 0.035). Intrauterine fetal deaths occurred only in
      women with a retroplacental hematoma (p = 0.042). CONCLUSIONS: Intra- and
      retroplacental hematomas have different risk profiles for the affected pregnancy
      and act as independent risk factors.

PMID- 29073891
TI  - Changes in prevalence, awareness, treatment and control of hypertension from 2004
      to 2014 among 25-74-year-old citizens in the Yangon Region, Myanmar.
AB  - BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases,
      and little is known about trends in prevalence, awareness, treatment and the
      control of hypertension in Myanmar. This study aims at evaluating changes from
      2004 to 2014 in the prevalence, awareness, treatment and control of hypertension
      in the Yangon Region, Myanmar, and to compare associations between hypertension
      and selected socio-demographic, behavioural- and metabolic risk factors in 2004
      and 2014. METHODS: In 2004 and 2014, household-based cross-sectional studies were
      conducted in urban and rural areas of Yangon Region using the WHO STEPS protocol.
      Through a multi-stage cluster sampling method, a total of 4448 and 1486
      participated in 2004 and 2014, respectively, with the response rates above 89%.
      RESULTS: From 2004 to 2014, there was a significant increase in the age
      standardized prevalence of hypertension from 26.7% (95% CI:24.4-29.1) - 34.6%
      (32.2-37.1), as well as an awareness from 19.4% (17.2-21.9) to 27.8% (24.9-31.0),
      while treatment and control rates did not change. The age-standardized mean
      systolic blood pressure increased from 122.8 (SE) +/- 0.82 mmHg in 2004 to 128.1
      +/- 0.53 mmHg in 2014, whereas diastolic blood pressure increased from 76.2 +/-
      0.35 mmHg to 80.9 +/- 0.53 mmHg. In multivariate analyses, hypertension was
      significantly associated with age, alcohol consumption, overweight and diabetes
      in both 2004 and 2014, and additionally associated with low physical activity and
      hypercholesterolemia in 2004. Combining all data, a significant association
      between study-year and hypertension persisted in different models with an
      adjustment for socio-demographic variables and behavioural variables, but not
      when adjusting for a combination of socio-demographic variables, the metabolic
      variables, BMI and hypercholesterolemia. CONCLUSION: The prevalence of
      hypertension has risen from 2004 to 2014 in both urban and rural areas of the
      Yangon Region, while, the awareness, treatment and control rate of hypertension
      remains low in urban and rural areas among both males and females. It is likely
      that changes in the metabolic variables, BMI and hypercholesterolemia have
      contributed to an increase in the prevalence of hypertension from 2004 to 2014.
      Factors associated with hypertension in both study years were age, alcohol
      consumption, overweight and diabetes. A national hypertension control programme
      should be implemented in order to reduce premature deaths in Myanmar.

PMID- 29073890
TI  - Prey preference follows phylogeny: evolutionary dietary patterns within the
      marine gastropod group Cladobranchia (Gastropoda: Heterobranchia: Nudibranchia).
AB  - BACKGROUND: The impact of predator-prey interactions on the evolution of many
      marine invertebrates is poorly understood. Since barriers to genetic exchange are
      less obvious in the marine realm than in terrestrial or freshwater systems, non
      allopatric divergence may play a fundamental role in the generation of
      biodiversity. In this context, shifts between major prey types could constitute
      important factors explaining the biodiversity of marine taxa, particularly in
      groups with highly specialized diets. However, the scarcity of marine specialized
      consumers for which reliable phylogenies exist hampers attempts to test the role
      of trophic specialization in evolution. In this study, RNA-Seq data is used to
      produce a phylogeny of Cladobranchia, a group of marine invertebrates that feed
      on a diverse array of prey taxa but mostly specialize on cnidarians. The broad
      range of prey type preferences allegedly present in two major groups within
      Cladobranchia suggest that prey type shifts are relatively common over
      evolutionary timescales. RESULTS: In the present study, we generated a well
      supported phylogeny of the major lineages within Cladobranchia using RNA-Seq
      data, and used ancestral state reconstruction analyses to better understand the
      evolution of prey preference. These analyses answered several fundamental
      questions regarding the evolutionary relationships within Cladobranchia,
      including support for a clade of species from Arminidae as sister to Tritoniidae
      (which both preferentially prey on Octocorallia). Ancestral state reconstruction
      analyses supported a cladobranchian ancestor with a preference for Hydrozoa and
      show that the few transitions identified only occur from lineages that prey on
      Hydrozoa to those that feed on other types of prey. CONCLUSIONS: There is strong
      phylogenetic correlation with prey preference within Cladobranchia, suggesting
      that prey type specialization within this group has inertia. Shifts between
      different types of prey have occurred rarely throughout the evolution of
      Cladobranchia, indicating that this may not have been an important driver of the
      diversity within this group.

PMID- 29073892
TI  - Multiple criteria decision analysis in the context of health technology
      assessment: a simulation exercise on metastatic colorectal cancer with multiple
      stakeholders in the English setting.
AB  - BACKGROUND: Multiple criteria decision analysis (MCDA) has appeared as a
      methodology to address limitations of economic evaluation in health technology
      assessment (HTA), however there are limited empirical evidence from real world
      applications. The aim of this study is to test in practice a recently developed
      MCDA methodological framework known as Advance Value Framework (AVF) through a
      proof-of-concept case study engaging multiple stakeholders. METHODS: A multi
      attribute value theory methodological process was adopted involving problem
      structuring, model building, model assessment and model appraisal phases. A
      facilitated decision analysis modelling approach was used as part of a decision
      conference with thirteen participants. An expanded scope of the National
      Institute for Health and Care Excellence (NICE) remit acted as the study setting
      with the use of supplementary value concerns. Second-line biological treatments
      were evaluated for metastatic colorectal cancer (mCRC) patients having received
      prior chemotherapy, including cetuximab monotherapy, panitumumab monotherapy and
      aflibercept in combination with FOLFIRI chemotherapy. Initially 18 criteria
      attributes were considered spanning four value domains relating to therapeutic
      impact, safety profile, innovation level and socioeconomic impact. RESULTS: Nine
      criteria attributes were finally included. Cetuximab scored the highest overall
      weighted preference value score of 45.7 out of 100, followed by panitumumab with
      42.3, and aflibercept plus FOLFIRI with 14.4. The relative weights of the two
      most important criteria (overall survival and Grade 4 adverse events) added up to
      more than the relative weight of all other criteria together (52.1%). Main
      methodological limitation was the lack of comparative clinical effects across
      treatments and challenges included the selection of "lower" and "higher"
      reference levels on criteria attributes, eliciting preferences across attributes
      where participants had less experience, and ensuring that all attributes possess
      the right decision theory properties. CONCLUSIONS: This first application of AVF
      produced transparent rankings for three mCRC treatments based on their value, by
      assessing an explicit set of evaluation criteria while allowing for the
      elicitation and construction of participants' value preferences and their trade
      offs. It proved it can aid the evaluation process and value communication of the
      alternative treatments for the group participants. Further research is needed to
      optimise its use as part of policy-making.

PMID- 29073893
TI  - Activity-dependent formation of a vesicular inhibitory amino acid transporter
      gradient in the superior olivary complex of NMRI mice.
AB  - BACKGROUND: In the mammalian superior olivary complex (SOC), synaptic inhibition
      contributes to the processing of binaural sound cues important for sound
      localization. Previous analyses demonstrated a tonotopic gradient for
      postsynaptic proteins mediating inhibitory neurotransmission in the lateral
      superior olive (LSO), a major nucleus of the SOC. To probe, whether a presynaptic
      molecular gradient exists as well, we investigated immunoreactivity against the
      vesicular inhibitory amino acid transporter (VIAAT) in the mouse auditory
      brainstem. RESULTS: Immunoreactivity against VIAAT revealed a gradient in the LSO
      and the superior paraolivary nucleus (SPN) of NMRI mice, with high expression in
      the lateral, low frequency processing limb and low expression in the medial, high
      frequency processing limb of both nuclei. This orientation is opposite to the
      previously reported gradient of glycine receptors in the LSO. Other nuclei of the
      SOC showed a uniform distribution of VIAAT-immunoreactivity. No gradient was
      observed for the glycine transporter GlyT2 and the neuronal protein NeuN.
      Formation of the VIAAT gradient was developmentally regulated and occurred around
      hearing-onset between postnatal days 8 and 16. Congenital deaf Claudin14 -/- mice
      bred on an NMRI background showed a uniform VIAAT-immunoreactivity in the LSO,
      whereas cochlear ablation in NMRI mice after hearing-onset did not affect the
      gradient. Additional analysis of C57Bl6/J, 129/SvJ and CBA/J mice revealed a
      strain-specific formation of the gradient. CONCLUSIONS: Our results identify an
      activity-regulated gradient of VIAAT in the SOC of NRMI mice. Its absence in
      other mouse strains adds a novel layer of strain-specific features in the
      auditory system, i.e. tonotopic organization of molecular gradients. This calls
      for caution when comparing data from different mouse strains frequently used in
      studies involving transgenic animals. The presence of strain-specific differences
      offers the possibility of genetic mapping to identify molecular factors involved
      in activity-dependent developmental processes in the auditory system. This would
      provide an important step forward concerning improved auditory rehabilitation in
      cases of congenital deafness.

PMID- 29073894
TI  - Propofol inhibits the release of interleukin-6, 8 and tumor necrosis factor-alpha
      correlating with high-mobility group box 1 expression in lipopolysaccharides
      stimulated RAW 264.7 cells.
AB  - BACKGROUND: Studies have found that propofol can inhibit endotoxin-induced
      monocyte-macrophages to produce various inflammatory factors. This study is to
      disclose whether the propofol affects the expression of high-mobility group box 1
      (HMGB1) in lipopolysaccharides (LPS)-stimulated RAW 264.7 cells and the release
      of interleukin-6 (IL-6), 8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha).
      METHODS: RAW 264.7 cells were divided into four groups for intervention. After
      culturing for 16 h, the cells and culture supernatants were collected. The
      expression of HMGB1 in RAW 264.7 cells was detected by Western blot. The levels
      of IL-6, IL-8 and TNF-alpha in supernatants of cells were determined by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Stimulation of LPS increased the
      expression of HMGB1 and promoted the release of IL-6, IL-8 and TNF-alpha in
      supernatants of RAW 264.7 cells (p < 0.05); however, propofol down-regulated the
      expression of LPS-stimulated HMGB1 and reduced the LPS-stimulated releases of IL
      6, IL-8 and TNF-alpha in supernatants of RAW 264.7 cells (p < 0.05). Moreover,
      the releases of IL-6, IL-8 and TNF-alpha intimately correlated with the
      expression of HMGB1 in this process (p < 0.05). CONCLUSION: Propofol inhibited
      the releases of IL-6, IL-8 and TNF-alpha in LPS-stimulated RAW 264.7 cells, and
      the levels of IL-6, IL-8 and TNF-alpha intimately correlated with the expression
      of HMGB1, which indicating that propofol may prevent inflammatory responses
      through reducing the releases of these cytokines and inflammatory mediators.

PMID- 29073895
TI  - Spatial phylogenetics of the native California flora.
AB  - BACKGROUND: California is a world floristic biodiversity hotspot where the terms
      neo- and paleo-endemism were first applied. Using spatial phylogenetics, it is
      now possible to evaluate biodiversity from an evolutionary standpoint, including
      discovering significant areas of neo- and paleo-endemism, by combining spatial
      information from museum collections and DNA-based phylogenies. Here we used a
      distributional dataset of 1.39 million herbarium specimens, a phylogeny of 1083
      operational taxonomic units (OTUs) and 9 genes, and a spatial randomization test
      to identify regions of significant phylogenetic diversity, relative phylogenetic
      diversity, and phylogenetic endemism (PE), as well as to conduct a categorical
      analysis of neo- and paleo-endemism (CANAPE). RESULTS: We found (1) extensive
      phylogenetic clustering in the South Coast Ranges, southern Great Valley, and
      deserts of California; (2) significant concentrations of short branches in the
      Mojave and Great Basin Deserts and the South Coast Ranges and long branches in
      the northern Great Valley, Sierra Nevada foothills, and the northwestern and
      southwestern parts of the state; (3) significant concentrations of paleo-endemism
      in Northwestern California, the northern Great Valley, and western Sonoran
      Desert, and neo-endemism in the White-Inyo Range, northern Mojave Desert, and
      southern Channel Islands. Multiple analyses were run to observe the effects on
      significance patterns of using different phylogenetic tree topologies
      (uncalibrated trees versus time-calibrated ultrametric trees) and using different
      representations of OTU ranges (herbarium specimen locations versus species
      distribution models). CONCLUSIONS: These analyses showed that examining the
      geographic distributions of branch lengths in a statistical framework adds a new
      dimension to California floristics that, in comparison with climatic data, helps
      to illuminate causes of endemism. In particular, the concentration of significant
      PE in more arid regions of California extends previous ideas about aridity as an
      evolutionary stimulus. The patterns seen are largely robust to phylogenetic
      uncertainty and time calibration but are sensitive to the use of occurrence data
      versus modeled ranges, indicating that special attention toward improving
      geographic distributional data should be top priority in the future for advancing
      understanding of spatial patterns of biodiversity.

PMID- 29073897
TI  - A comparative study of multiple clinical enterovirus 71 isolates and evaluation
      of cross protection of inactivated vaccine strain FY-23 K-B in vitro.
AB  - BACKGROUND: Enterovirus 71 (EV71) is one of the causative agents of hand, foot
      and mouth disease, which mostly affects infants and children and leads to severe
      neurological diseases. Vaccination offers the best option for disease control. We
      have screened the virus strain FY-23 K-B, which is used as an inactivated vaccine
      strain. An important issue in the development of vaccines is whether they provide
      cross protection against all other strains. METHODS: We collected and identified
      19 clinical EV71 isolates from mainland China, which all belong to the C4
      genotype. We established growth curves of the strains in Vero cells, performed
      genetic analysis, and evaluated the cross protection efficacy through
      neutralizing assays using antisera from a rabbit, monkey and adult human
      immunized with the FY-23 K-B vaccine strain. RESULTS: The antisera showed broad
      cross protection among the C4 subgroup strains and homotype strain. Neutralizing
      indexes (NIs) among the isolates and homotype strain of antisera varied between
      56.2-1995.3 for rabbit, 17.8-42,169.7 for monkey and 31.6-17,782.8 for human,
      whereas NIs against Coxsackievirus A16 or other enteroviruses were below 10.
      CONCLUSIONS: These results suggested that FY-23 K-B used as an antigen could
      elicit broad spectrum neutralizing antibodies with cross protective efficacy
      among C4 genotype strains.

PMID- 29073896
TI  - Lipid metabolism fattens up hedgehog signaling.
AB  - Signaling pathways direct organogenesis, often through concentration-dependent
      effects on cells. The hedgehog pathway enables cells to sense and respond to
      hedgehog ligands, of which the best studied is sonic hedgehog. Hedgehog signaling
      is essential for development, proliferation, and stem cell maintenance, and it is
      a driver of certain cancers. Lipid metabolism has a profound influence on both
      hedgehog signal transduction and the properties of the ligands themselves,
      leading to changes in the strength of hedgehog signaling and cellular functions.
      Here we review the evolving understanding of the relationship between lipids and
      hedgehog signaling.

PMID- 29073898
TI  - Sexual conflict explains the extraordinary diversity of mechanisms regulating
      mitochondrial inheritance.
AB  - BACKGROUND: Mitochondria are predominantly inherited from the maternal gamete,
      even in unicellular organisms. Yet an extraordinary array of mechanisms enforce
      uniparental inheritance, which implies shifting selection pressures and multiple
      origins. RESULTS: We consider how this high turnover in mechanisms controlling
      uniparental inheritance arises using a novel evolutionary model in which control
      of mitochondrial transmission occurs either during spermatogenesis (by paternal
      nuclear genes) or at/after fertilization (by maternal nuclear genes). The model
      treats paternal leakage as an evolvable trait. Our evolutionary analysis shows
      that maternal control consistently favours strict uniparental inheritance with
      complete exclusion of sperm mitochondria, whereas some degree of paternal leakage
      of mitochondria is an expected outcome under paternal control. This difference
      arises because mito-nuclear linkage builds up with maternal control, allowing the
      greater variance created by asymmetric inheritance to boost the efficiency of
      purifying selection and bring benefits in the long term. In contrast, under
      paternal control, mito-nuclear linkage tends to be much weaker, giving greater
      advantage to the mixing of cytotypes, which improves mean fitness in the short
      term, even though it imposes a fitness cost to both mating types in the long
      term. CONCLUSIONS: Sexual conflict is an inevitable outcome when there is
      competition between maternal and paternal control of mitochondrial inheritance.
      If evolution has led to complete uniparental inheritance through maternal
      control, it creates selective pressure on the paternal nucleus in favour of
      subversion through paternal leakage, and vice versa. This selective divergence
      provides a reason for the repeated evolution of novel mechanisms that regulate
      the transmission of paternal mitochondria, both in the fertilized egg and
      spermatogenesis. Our analysis suggests that the widespread occurrence of paternal
      leakage and prevalence of heteroplasmy are natural outcomes of this sexual
      conflict.

PMID- 29073899
TI  - Validation of the 5-item doctor-patient communication competency instrument for
      medical students (DPCC-MS) using two years of assessment data.
AB  - BACKGROUND: Medical students on clinical rotations have to be assessed on several
      competencies at the end of each clinical rotation, pointing to the need for
      short, reliable, and valid assessment instruments of each competency. Doctor
      patient communication is a central competency targeted by medical schools
      however, there are no published short (i.e. less than 10 items), reliable and
      valid instruments to assess doctor-patient communication competency. The Faculty
      of Medicine of Laval University recently developed a 5-item Doctor-Patient
      Communication Competency instrument for Medical Students (DPCC-MS), based on the
      Patient Centered Clinical Method conceptual framework, which provides a global
      summative end-of-rotation assessment of doctor-patient communication. We
      conducted a psychometric validation of this instrument and present validity
      evidence based on the response process, internal structure and relation to other
      variables using two years of assessment data. METHODS: We conducted the study in
      two phases. In phase 1, we drew on 4991 student DPCC-MS assessments (two years).
      We conducted descriptive statistics, a confirmatory factor analysis (CFA), and
      tested the correlation between the DPCC-MS and the Multiple Mini Interviews (MMI)
      scores. In phase 2, eleven clinical teachers assessed the performance of 35
      medical students in an objective structured clinical examination station using
      the DPCC-MS, a 15-item instrument developed by Cote et al. (published in 2001),
      and a 2-item global assessment. We compared the DPCC-MS to the longer Cote et al.
      instrument based on internal consistency, coefficient of variation, convergent
      validity, and inter-rater reliability. RESULTS: Phase 1: Cronbach's alpha was
      acceptable (.75 and .83). Inter-item correlations were positive and the
      discrimination index was above .30 for all items. CFA supported a unidimensional
      structure. DPCC-MS and MMI scores were correlated. Phase 2: The DPCC-MS and the
      Cote et al. instrument had similar internal consistency and convergent validity,
      but the DPCC-MS had better inter-rater reliability (mean ICC = .61). CONCLUSIONS:
      The DPCC-MS provides an internally consistent and valid assessment of medical
      students' communication with patients.

PMID- 29073900
TI  - Comparison of online marketing techniques on food and beverage companies'
      websites in six countries.
AB  - Food and beverage marketing contributes to poor dietary choices among adults and
      children. As consumers spend more time on the Internet, food and beverage
      companies have increased their online marketing efforts. Studies have shown food
      companies' online promotions use a variety of marketing techniques to promote
      mostly energy-dense, nutrient-poor products, but no studies have compared the
      online marketing techniques and nutritional quality of products promoted on food
      companies' international websites. For this descriptive study, we developed a
      qualitative codebook to catalogue the marketing themes used on 18 international
      corporate websites associated with the world's three largest fast food and
      beverage companies (i.e. Coca-Cola, McDonald's, Kentucky Fried Chicken).
      Nutritional quality of foods featured on those websites was evaluated based on
      quantitative Nutrient Profile Index scores and food category (e.g. fried, fresh).
      Beverages were sorted into categories based on added sugar content. We report
      descriptive statistics to compare the marketing techniques and nutritional
      quality of products featured on the company websites for the food and beverage
      company websites in two high-income countries (HICs), Germany and the United
      States, two upper-middle-income countries (UMICs), China and Mexico, and two
      lower-middle-income countries (LMICs), India and the Philippines. Of the 406
      screenshots captured from company websites, 67.8% depicted a food or beverage
      product. HICs' websites promoted diet food or beverage products/healthier
      alternatives (e.g. baked chicken sandwich) significantly more often on their
      pages (25%), compared to LMICs (14.5%). Coca-Cola featured diet products
      significantly more frequently on HIC websites compared to LMIC websites.
      Charities were featured more often on webpages in LMICs (15.4%) compared to UMICs
      (2.6%) and HICs (2.3%). This study demonstrates that companies showcase healthier
      products in wealthier countries and advertise their philanthropic activities in
      lower income countries, which is concerning given the negative effect of
      nutrition transition (double burden of overnutrition and undernutrition) on
      burden of non-communicable diseases and obesity in lower income countries.

PMID- 29073901
TI  - Statistical methods to derive efficacy estimates of anti-malarials for
      uncomplicated Plasmodium falciparum malaria: pitfalls and challenges.
AB  - The Kaplan-Meier (K-M) method is currently the preferred approach to derive an
      efficacy estimate from anti-malarial trial data. In this approach event times are
      assumed to be continuous and estimates are generated on the assumption that there
      is only one cause of failure. In reality, failures are captured at pre-scheduled
      time points and patients can fail treatment due to a variety of causes other than
      the primary endpoint, commonly termed competing risk events. Ignoring these
      underlying assumptions can potentially distort the derived efficacy estimates and
      result in misleading conclusions. This review details the evolution of
      statistical methods used to derive anti-malarial efficacy for uncomplicated
      Plasmodium falciparum malaria and assesses the limitations of the current
      practices. Alternative approaches are explored and their implementation is
      discussed using example data from a large multi-site study.

PMID- 29073902
TI  - Clinical and radiographic evaluation of pulpectomy in primary teeth: a 18-months
      clinical randomized controlled trial.
AB  - BACKGROUND: To avoid untoward changes when primary teeth are replaced by
      permanent teeth, resorption of the material used in primary teeth root canal
      filling should occur at the same rate as root resorption. The Aim of this study
      was to compare the success rates of a mixed primary root canal filling (MPRCF,
      ingredients: zinc oxide-eugenol [ZOE], iodoform, calcium hydroxide) to those of
      ZOE and Vitapex in pulpectomised primary molars. METHODS: One hundred and sixty
      primary molars from 155 children (average age 5.88 +/- 1.27 years) underwent two
      visit pulpectomy using one of the three materials. The clinical and radiographic
      findings at 6, 12 and 18 months were assessed. RESULTS: At 6 and 12 months, the
      MPRCF and ZOE success rates were 100%. The Vitapex group showed clinical success
      rate and radiographic success rate of 100 and 94.5% at 6 months, and 80.4 and
      60.7% at 12 months. The 18-month clinical success rates of the MPRCF, ZOE and
      Vitapex were 96.2, 92.2 and 71.4% and radiographic success rates were 92.5, 88.2
      and 53.6%, respectively. There was a statistically significant difference in the
      success rates between MPRCF and Vitapex and no significant differences between
      MPRCF and ZOE. More MPRCF were resorbed at same rate with roots than ZOE and
      Vitapex. Early resorption of root filling resulted in more failure. CONCLUSIONS:
      The mixture of ZOE, iodoform and calcium hydroxide can be considered an effective
      root canal filling material in pulp involved primary teeth and had no adverse
      effect on tooth replacement. TRIAL REGISTRATION: ChiCTR-TRC-14004938 . Registered
      13 July 2014.

PMID- 29073903
TI  - Characterizing endophytic competence and plant growth promotion of bacterial
      endophytes inhabiting the seed endosphere of Rice.
AB  - BACKGROUND: Rice (Oryza sativa L. ssp. indica) seeds as plant microbiome present
      both an opportunity and a challenge to colonizing bacterial community living in
      close association with plants. Nevertheless, the roles and activities of
      bacterial endophytes remain largely unexplored and insights into plant-microbe
      interaction are compounded by its complexity. In this study, putative functions
      or physiological properties associated with bacterial endophytic nature were
      assessed. Also, endophytic roles in plant growth and germination that may allow
      them to be selectively chosen by plants were also studied. RESULTS: The
      cultivable seed endophytes were dominated by Proteobacteria particularly class
      Gammaproteobacteria. Highly identical type strains were isolated from the seed
      endosphere regardless of the rice host's physiological tolerance to salinity.
      Among the type strains, Flavobacterium sp., Microbacterium sp. and Xanthomonas
      sp. were isolated from the salt-sensitive and salt-tolerant cultivars. PCA-Biplot
      ordination also showed that specific type strains isolated from different rice
      cultivars have distinguishing similar characteristics. Flavobacterium sp. strains
      are phosphate solubilizers and indole-3-acetic acid producers with high tolerance
      to salinity and osmotic stress. Pseudomonas strains are characterized as high
      siderophore producers while Microbacterium sp. and Xanthomonas sp. strains have
      very high pectinase and cellulase activity. Among the physiological traits of the
      seed endophytes, bacterial pectinase and cellulase activity are positively
      correlated as well as salt and osmotic tolerance. Overall characterization shows
      that majority of the isolates could survive in 4-8% salt concentration as well as
      in 0.6 M and 1.2 M sucrose solution. The activities of catalase, pectinase and
      cellulase were also observed in almost all of the isolates indicating the
      importance of these characteristics for survival and colonization into the seed
      endosphere. Seed bacterial endophytes also showed promising plant growth
      promoting activities including hormone modulation, nitrogen fixation, siderophore
      production and phosphate solubilization. CONCLUSION: Though many of the isolates
      possess similar PGP and endophytic physiological traits, this study shows some
      prominent and distinguishing traits among bacterial groups indicating key
      determinants for their success as endophytes in the rice seed endosphere. Rice
      seeds are also inhabited by bacterial endophytes that promote growth during early
      seedling development.

PMID- 29073904
TI  - Detecting the tipping points in a three-state model of complex diseases by
      temporal differential networks.
AB  - BACKGROUND: The progression of complex diseases, such as diabetes and cancer, is
      generally a nonlinear process with three stages, i.e., normal state, pre-disease
      state, and disease state, where the pre-disease state is a critical state or
      tipping point immediately preceding the disease state. Traditional biomarkers aim
      to identify a disease state by exploiting the information of differential
      expressions for the observed molecules, but may fail to detect a pre-disease
      state because there are generally little significant differences between the
      normal and pre-disease states. Thus, it is challenging to signal the pre-disease
      state, which actually implies the disease prediction. METHODS: In this work, by
      exploiting the information of differential associations among the observed
      molecules between the normal and pre-disease states, we propose a temporal
      differential network based computational method to accurately signal the pre
      disease state or predict the occurrence of severe disease. The theoretical
      foundation of this work is the quantification of the critical state using
      dynamical network biomarkers. RESULTS: Considering that there is one stationary
      Markov process before reaching the tipping point, a novel index, inconsistency
      score (I-score), is proposed to quantitatively measure the change of the
      stationary processes from the normal state so as to detect the onset of pre
      disease state. In other words, a drastic increase of I-score implies the high
      inconsistency with the preceding stable state and thus signals the upcoming
      critical transition. This approach is applied to the simulated and real datasets
      of three diseases, which demonstrates the effectiveness of our method for
      predicting the deterioration into disease states. Both functional analysis and
      pathway enrichment also validate the computational results from the perspectives
      of both molecules and networks. CONCLUSIONS: At the molecular network level, this
      method provides a computational way of unravelling the underlying mechanism of
      the dynamical progression when a biological system is near the tipping point, and
      thus detecting the early-warning signal of the imminent critical transition,
      which may help to achieve timely intervention. Moreover, the rewiring of
      differential networks effectively extracts discriminatively interpretable
      features, and systematically demonstrates the dynamical change of a biological
      system.

PMID- 29073906
TI  - HDR syndrome with a novel mutation in GATA3 mimicking a congenital X-linked
      stapes gusher: a case report.
AB  - BACKGROUND: Hypoparathyroidism, sensorineural hearing loss, and renal disease
      (HDR) syndrome, also known as Barakat syndrome, is a rare genetic disorder with
      high phenotypic heterogeneity caused by haploinsufficiency of the GATA3 gene on
      chromosome 10p14-p15. For these reasons, the diagnosis of HDR syndrome is
      challenging and requires a high index of suspicion as well as genetic analysis.
      CASE PRESENTATION: A 14-month-old boy, with sensorineural hearing loss in both
      ears, showed typical radiological features of X-linked stapes gusher on
      preoperative temporal bone computed tomography (CT) for cochlear implantations.
      Then after his discharge from hospital, he suffered a hypocalcemic seizure and we
      discovered a renal cyst during investigation of hypocalcemia. He was finally
      diagnosed with HDR syndrome by clinical findings, which were confirmed by
      molecular genetic testing. Direct sequencing of the GATA3 gene showed a
      heterozygous 2-bp deletion (c.1201_1202delAT), which is predicted to cause a
      frameshift of the reading frame (p.Met401Valfs*106). CONCLUSIONS: To our
      knowledge, this is the first case of HDR syndrome with a novel de novo variant
      mimicking a congenital X-linked stapes gusher syndrome. Novel mutations and the
      diversity of clinical manifestations expand the genotypic and phenotypic spectrum
      of HDR syndrome. Diagnosis of HDR syndrome is still challenging, but clinicians
      should consider it in their differential diagnosis for children with a wide range
      of clinical manifestations including hypocalcemia induced seizures and deafness.
      We hope that this case will contribute to further understanding and studies of
      HDR-associated GATA3 mutations.

PMID- 29073905
TI  - Therapeutic application of T regulatory cells in composite tissue
      allotransplantation.
AB  - With growing number of cases in recent years, composite tissue
      allotransplantation (CTA) has been improving the quality of life of patient who
      seeks reconstruction and repair of damaged tissues. Composite tissue allografts
      are heterogeneous. They are composed of a variety of tissue types, including
      skin, muscle, vessel, bone, bone marrow, lymph nodes, nerve, and tendon. As a
      primary target of CTA, skin has high antigenicity with a rich repertoire of
      resident cells that play pivotal roles in immune surveillance. In this regard,
      understanding the molecular mechanisms involved in immune rejection in the skin
      would be essential to achieve successful CTA. Although scientific evidence has
      proved the necessity of immunosuppressive drugs to prevent rejection of
      allotransplanted tissues, there remains a lingering dilemma due to the lack of
      specificity of targeted immunosuppression and risks of side effects. A cumulative
      body of evidence has demonstrated T regulatory (Treg) cells have critical roles
      in induction of immune tolerance and immune homeostasis in preclinical and
      clinical studies. Presently, controlling immune susceptible characteristics of
      CTA with adoptive transfer of Treg cells is being considered promising and it has
      drawn great interests. This updated review will focus on a dominant form of Treg
      cells expressing CD4+CD25+ surface molecules and a forkhead box P3 transcription
      factor with immune tolerant and immune homeostasis activities. For future
      application of Treg cells as therapeutics in CTA, molecular and cellular
      characteristics of CTA and immune rejection, Treg cell development and
      phenotypes, Treg cell plasticity and stability, immune tolerant functions of Treg
      cells in CTA in preclinical studies, and protocols for therapeutic application of
      Treg cells in clinical settings are addressed in this review. Collectively, Treg
      cell therapy in CTA seems feasible with promising perspectives. However, the
      extreme high immunogenicity of CTA warrants caution.

PMID- 29073907
TI  - Multiparametric analysis of anti-proliferative and apoptotic effects of gold
      nanoprisms on mouse and human primary and transformed cells, biodistribution and
      toxicity in vivo.
AB  - BACKGROUND: The special physicochemical properties of gold nanoprisms make them
      very useful for biomedical applications including biosensing and cancer therapy.
      However, it is not clear how gold nanoprisms may affect cellular physiology
      including viability and other critical functions. We report a multiparametric
      investigation on the impact of gold-nanoprisms on mice and human, transformed and
      primary cells as well as tissue distribution and toxicity in vivo after parental
      injection. METHODS: Cellular uptake of the gold-nanoprisms (NPRs) and the most
      crucial parameters of cell fitness such as generation of reactive oxygen species
      (ROS), mitochondria membrane potential, cell morphology and apoptosis were
      systematically assayed in cells. Organ distribution and toxicity including
      inflammatory response were analysed in vivo in mice at 3 days or 4 months after
      parental administration. RESULTS: Internalized gold-nanoprisms have a significant
      impact in cell morphology, mitochondrial function and ROS production, which
      however do not affect the potential of cells to proliferate and form colonies. In
      vivo NPRs were only detected in spleen and liver at 3 days and 4 months after
      administration, which correlated with some changes in tissue architecture.
      However, the main serum biochemical markers of organ damage and inflammation
      (TNFalpha and IFNgamma) remained unaltered even after 4 months. In addition,
      animals did not show any macroscopic sign of toxicity and remained healthy during
      all the study period. CONCLUSION: Our data indicate that these gold-nanoprisms
      are neither cytotoxic nor cytostatic in transformed and primary cells, and
      suggest that extensive parameters should be analysed in different cell types to
      draw useful conclusions on nanomaterials safety. Moreover, although there is a
      tendency for the NPRs to accumulate in liver and spleen, there is no observable
      negative impact on animal health.

PMID- 29073908
TI  - Explaining discrepancies in self-reported quality of life in frail older people:
      a mixed-methods study.
AB  - BACKGROUND: Most research on multidimensional frailty focuses on deficits and
      risks of adverse outcomes. However, although some frail older people report a low
      quality of life (QoL), others still report a relatively high QoL. More knowledge
      about these discrepancies might give new insight into developing frailty
      prevention strategies. Therefore, this mixed-method study aimed (a) to identify
      characteristics related to QoL among frail older people; and (b) to explain
      discrepancies between higher and lower levels of QoL, with a specific interest in
      identifying strengths frail older people with a higher QoL still have. METHODS:
      Semi-structured interviews were held with community-dwelling, frail older people
      with higher (n = 16) and lower levels of QoL (n = 18). Frailty was assessed with
      the Comprehensive Frailty Assessment Instrument, which measures environmental,
      physical, psychological, and social frailty. Other quantitative measures included
      socio-demographic characteristics, overall QoL, meaning in life, and mastery. The
      qualitative part focused on the meaning and maintenance of QoL (among other
      factors), despite being frail. Possible explanations for discrepancies in QoL
      were explored. RESULTS: Frail older people with a higher QoL were older, had
      lower levels of psychological frailty, and reported higher meaning in life
      compared to those with a lower QoL. Outcomes of qualitative analysis showed that
      participants in the high QoL subgroup adapted more effectively to difficulties,
      had more things in prospect, performed more activities, and were more satisfied
      with their social network compared to the low QoL subgroup. CONCLUSION: This
      exploratory study suggests possibilities to promote and improve QoL by
      strengthening specific resources among frail older people.

PMID- 29073909
TI  - Genotype-driven identification of a molecular network predictive of advanced
      coronary calcium in ClinSeq(r) and Framingham Heart Study cohorts.
AB  - BACKGROUND: One goal of personalized medicine is leveraging the emerging tools of
      data science to guide medical decision-making. Achieving this using disparate
      data sources is most daunting for polygenic traits. To this end, we employed
      random forests (RFs) and neural networks (NNs) for predictive modeling of
      coronary artery calcium (CAC), which is an intermediate endo-phenotype of
      coronary artery disease (CAD). METHODS: Model inputs were derived from advanced
      cases in the ClinSeq(r); discovery cohort (n=16) and the FHS replication cohort
      (n=36) from 89 th -99 th CAC score percentile range, and age-matched controls
      (ClinSeq(r); n=16, FHS n=36) with no detectable CAC (all subjects were Caucasian
      males). These inputs included clinical variables and genotypes of 56 single
      nucleotide polymorphisms (SNPs) ranked highest in terms of their nominal
      correlation with the advanced CAC state in the discovery cohort. Predictive
      performance was assessed by computing the areas under receiver operating
      characteristic curves (ROC-AUC). RESULTS: RF models trained and tested with
      clinical variables generated ROC-AUC values of 0.69 and 0.61 in the discovery and
      replication cohorts, respectively. In contrast, in both cohorts, the set of SNPs
      derived from the discovery cohort were highly predictive (ROC-AUC >=0.85) with no
      significant change in predictive performance upon integration of clinical and
      genotype variables. Using the 21 SNPs that produced optimal predictive
      performance in both cohorts, we developed NN models trained with ClinSeq(r); data
      and tested with FHS data and obtained high predictive accuracy (ROC-AUC=0.80
      0.85) with several topologies. Several CAD and "vascular aging" related
      biological processes were enriched in the network of genes constructed from the
      predictive SNPs. CONCLUSIONS: We identified a molecular network predictive of
      advanced coronary calcium using genotype data from ClinSeq(r); and FHS cohorts.
      Our results illustrate that machine learning tools, which utilize complex
      interactions between disease predictors intrinsic to the pathogenesis of
      polygenic disorders, hold promise for deriving predictive disease models and
      networks.

PMID- 29073911
TI  - Successful transition from Treprostinil to Selexipag in patient with severe
      pulmonary arterial hypertension.
AB  - BACKGROUND: In this report, we describe the first successful case of transition
      from subcutaneous administration of treprostinil to selexipag in a patient with
      severe pulmonary arterial hypertension (PAH), by evaluating hemodynamic changes
      and exercise tolerance. CASE PRESENTATION: A 38-year-old female with idiopathic
      PAH (IPAH) had received initial triple combination therapy (macitentan PO,
      tadalafil PO, and treprostinil SC) and achieved excellent improvement in
      hemodynamics. Afterwards, due to the development of side effects from
      subcutaneous administration, we replaced treprostinil therapy with oral
      selexipag, resulting in stable hemodynamic parameters and exercise capacities.
      CONCLUSIONS: We report the first case of successful replacement of treprostinil
      (20.1 ng/kg/min) with selexipag (1600 MUg BID) as a component of triple
      combination therapy, which provides incentive to perform a larger, prospective
      exchange study.

PMID- 29073910
TI  - Spot sputum samples are at least as good as early morning samples for identifying
      Mycobacterium tuberculosis.
AB  - BACKGROUND: The use of early morning sputum samples (EMS) to diagnose
      tuberculosis (TB) can result in treatment delay given the need for the patient to
      return to the clinic with the EMS, increasing the chance of patients being lost
      during their diagnostic workup. However, there is little evidence to support the
      superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB
      study, we compare the diagnostic accuracy of EMS with spot samples for
      identifying Mycobacterium tuberculosis pre- and post-treatment. METHODS: Patients
      who were smear positive at screening were enrolled into the study. Paired sputum
      samples (one EMS and one spot) were collected at each trial visit pre- and post
      treatment. Microscopy and culture on solid LJ and liquid MGIT media were
      performed on all samples; those missing corresponding paired results were
      excluded from the analyses. RESULTS: Data from 1115 pre- and 2995 post-treatment
      paired samples from 1931 patients enrolled in the REMoxTB study were analysed.
      Patients were recruited from South Africa (47%), East Africa (21%), India (20%),
      Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24
      41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/MUL
      (IQR 318-535). Pre-treatment spot samples had a higher yield of positive Ziehl
      Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006)
      than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P =
      0.18). Contaminated and false-positive MGIT were found more often with EMS rather
      than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and
      shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs.
      5.5 days, P < 0.001). There were no differences in time to positivity in pre
      treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and
      spot samples in those with unfavourable outcomes, there were no differences in
      smear or culture results, and positive results were not detected earlier in
      Kaplan-Meier analyses in either EMS or spot samples. CONCLUSIONS: Our data do not
      support the hypothesis that EMS samples are superior to spot sputum samples in a
      clinical trial of patients with smear positive pulmonary TB. Observed small
      differences in mycobacterial burden are of uncertain significance and EMS samples
      do not detect post-treatment positives any sooner than spot samples.

PMID- 29073912
TI  - Automatic non-proliferative diabetic retinopathy screening system based on color
      fundus image.
AB  - BACKGROUND: Non-proliferative diabetic retinopathy is the early stage of diabetic
      retinopathy. Automatic detection of non-proliferative diabetic retinopathy is
      significant for clinical diagnosis, early screening and course progression of
      patients. METHODS: This paper introduces the design and implementation of an
      automatic system for screening non-proliferative diabetic retinopathy based on
      color fundus images. Firstly, the fundus structures, including blood vessels,
      optic disc and macula, are extracted and located, respectively. In particular, a
      new optic disc localization method using parabolic fitting is proposed based on
      the physiological structure characteristics of optic disc and blood vessels.
      Then, early lesions, such as microaneurysms, hemorrhages and hard exudates, are
      detected based on their respective characteristics. An equivalent optical model
      simulating human eyes is designed based on the anatomical structure of retina.
      Main structures and early lesions are reconstructed in the 3D space for better
      visualization. Finally, the severity of each image is evaluated based on the
      international criteria of diabetic retinopathy. RESULTS: The system has been
      tested on public databases and images from hospitals. Experimental results
      demonstrate that the proposed system achieves high accuracy for main structures
      and early lesions detection. The results of severity classification for non
      proliferative diabetic retinopathy are also accurate and suitable. CONCLUSIONS:
      Our system can assist ophthalmologists for clinical diagnosis, automatic
      screening and course progression of patients.

PMID- 29073913
TI  - Correction to: Adaptation of the 2015 American College of Rheumatology treatment
      guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an
      exemplar of the GRADE Adolopment.

PMID- 29073914
TI  - Measuring mistreatment of women during childbirth: a review of terminology and
      methodological approaches.
AB  - BACKGROUND: Although mistreatment of women during facility-based childbirth has
      received increasing recognition as a critical issue throughout the world, there
      remains a lack of consensus on operational definitions of mistreatment and best
      practices to assess the issue. Moreover, only minimal research has focused on
      mistreatment in Latin America and the Caribbean, a region notable for social
      inequalities and inequitable access to maternal health care. METHODS: In this
      article, we discuss the results of a literature review that sought to contribute
      to the determination of best practices in defining and measuring the mistreatment
      of women during childbirth, particularly within Latin America and the Caribbean.
      The review includes a total of 57 English, Spanish, and Portuguese-language
      research publications and eight legal documents that were published between 2000
      and 2017. RESULTS: While the typologies of "disrespect and abuse" and
      "mistreatment during facility-based childbirth" are most frequently employed in
      global studies, "obstetric violence" remains the most commonly operationalized
      term in Latin America and the Caribbean in both research and policy contexts.
      Various researchers have advocated for the use of those three different
      typologies, yet the terms all share commonalities in highlighting the
      medicalization of natural processes of childbirth, roots in gender inequalities,
      parallels with violence against women, the potential for harm, and the threat to
      women's rights. For measuring mistreatment, half of the research publications in
      this review use qualitative methods, such as in-depth interviews and focus
      groups. After analyzing the strengths and limitations of quantitative,
      qualitative, and mixed methods approaches to assessing mistreatment, we recommend
      mixed methods designs as the optimal strategy to evaluate mistreatment and
      advocate for the inclusion of direct observations that may help bridge the gap
      between observed measures and participants' self-reported experiences of
      mistreatment. CONCLUSIONS: No matter the conceptual framework used in future
      investigations, we recommend that studies seek to accomplish three objectives:
      (1) to measure the perceived and observed frequencies of mistreatment in maternal
      health settings, (2) to examine the macro and micro level factors that drive
      mistreatment, and (3) to assess the impact of mistreatment on the health outcomes
      of women and their newborns.

PMID- 29073915
TI  - EMT-led laryngeal tube vs. face-mask ventilation during cardiopulmonary
      resuscitation - a multicenter prospective randomized trial.
AB  - BACKGROUND: Laryngeal tube (LT) application by rescue personnel as an alternate
      airway during the early stages of out-of-hospital cardiac arrest (OHCA) is still
      subject of debate. We evaluated ease of handling and efficacy of ventilation
      administered by emergency medical technicians (EMTs) using LT and bag-valve-mask
      (BVM) during cardiopulmonary resuscitation of patients with OHCA. METHODS: An
      open prospective randomized multicenter study was conducted at six emergency
      medical services centers over 18 months. Patients in OHCA initially resuscitated
      by EMTs were enrolled. Ease of handling (LT insertion, tight seal) and efficacy
      of ventilation (chest rises visibly, no air leak) with LT and BVM were
      subjectively assessed by EMTs during pre-study training and by the attending
      emergency physician on the scene. Outcome and frequency of complications were
      compared. RESULTS: Of 97 eligible patients, 78 were enrolled. During pre-study
      training EMTs rated efficacy of ventilation with LT higher than with BVM (66.7%
      vs. 36.2%, p = 0.022), but efficacy of on-site ventilation did not differ between
      the two groups (71.4% vs. 58.5%, p = 0.686). Frequency of complications (11.4%
      vs. 19.5%, p = 0.961) did not differ between the two groups. CONCLUSIONS: EMTs
      preferred LT ventilation to BVM ventilation during pre-study training, but on
      site there was no difference with regard to efficacy, ventilation safety, or
      outcome. The results indicate that LT ventilation by EMTs during OHCA is not
      superior to BVM and cannot substitute for BVM training. We assume that the main
      benefit of the LT is the provision of an alternative airway when BVM ventilation
      fails. Training in BVM ventilation remains paramount in EMT apprenticeship and
      cannot be substituted by LT ventilation. TRIAL REGISTRATION: ClinicalTrials.gov
      (NCT01718795).

PMID- 29073916
TI  - Participant recruitment and retention in longitudinal preconception randomized
      trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.
AB  - BACKGROUND: The preconception period has the potential to influence pregnancy
      outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety
      of potentially beneficial preconception interventions. However, RCTs commencing
      before pregnancy have significant participant recruitment and retention
      challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health
      Organization multi-country RCT of calcium supplementation commenced before
      pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants
      are recruited and followed up until childbirth. This sub-study explores
      recruitment methods and preconception retention of participants of the CAP trial
      to inform future trials. METHODS: Recruiters at the study sites in Argentina,
      South Africa and Zimbabwe completed post-recruitment phase questionnaires on
      recruitment methods used. Qualitative data from these questionnaires and
      quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up
      to September 2016 are reported in this paper. RStudio (Version 0.99.903
      https://www.rstudio.org ) statistical software was used for summary statistics.
      RESULTS: Between July 2011 and 8 September 2016, 1354 women with previous pre
      eclampsia were recruited. Recruitment took 2 years longer than expected and was
      facilitated mainly through medical record/register and maternity ward/clinic
      based strategies. Recruiters highlighted difficulties associated with inadequate
      medical records, redundant patient contact details, and follow-up of temporarily
      ineligible women as some of the challenges faced. Whilst the attendance rates at
      pre-pregnancy visits were high (78% or more), visits often occurred later than
      scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5%
      (454/1354) within 1 year of randomization. CONCLUSIONS: In preconception trials,
      both retrospective and prospective methods are useful for recruiting eligible
      women with certain conditions. However, these are time-consuming in low-resource
      settings with suboptimal medical records and other challenges. Trial planners
      should ensure that trial budgets cover sufficient on-site researchers with pre
      trial training, and should consider using mobile phone and web-based electronic
      tools to optimize recruitment and retention. This should lead to greater
      efficiency and shorter trial durations. TRIAL REGISTRATION: Pan-African Clinical
      Trials Registry, Registration Number: PACTR201105000267371 . The trial was
      registered on 6 December 2016.

PMID- 29073917
TI  - Benefit of salvage total pharyngolaryngoesophagectomy for recurrent locally
      advanced head and neck cancer after radiotherapy.
AB  - BACKGROUND: The treatment modalities for recurrent locally advanced head and neck
      cancer failure after radiotherapy are limited with poor prognosis. Salvage supra
      radical operation seems to be an option. It has not been established which
      patients will benefit from salvage total pharyngolaryngoesophagectomy. METHODS:
      We retrospectively reviewed 66 patients with previously irradiated recurrent T4
      head and neck cancer who underwent salvage total pharyngolaryngoesophagectomy at
      our institution between January 2001 and June 2014. The clinical outcome and
      toxicities were analyzed. RESULTS: Flap loss occurred in 2 patients, and the
      incidence of fistulas and anastomosis strictures was 15.6% (10/66) and 13.6%
      (9/66), respectively. The median survival time of the entire cohort was 12
      months. The interval between radiation and salvage surgery, and microscopic
      carotid artery invasion were identified as independent prognostic factors for
      overall survival. The 3-year overall survival rates of patients with (n = 33) and
      without (n = 33) risk factors were 9.1% and 47.2%, respectively (p = 0.007). A
      time interval between radiation and salvage surgery <=6 months and previous
      concurrent chemotherapy or targeted therapy were risk factors for severe post
      operative complications. CONCLUSIONS: Salvage total pharyngolaryngoesophagectomy
      is beneficial to selected patients with recurrent locally advanced head and neck
      cancer after radiotherapy.

PMID- 29073918
TI  - A first description of the Colombian national registry for rare diseases.
AB  - OBJECTIVE: Orphan diseases must be considered a public health concern, underlying
      country-specific challenges for their accurate and opportune diagnosis,
      classification and management. Orphan disease registries have not yet been
      created in South America, a continent having a population of ~ 415 million
      inhabitants. In Colombia ~ 3 million of patients are affected by rare diseases.
      The aim of the present study was to establish the first Colombian national
      registry for rare diseases. The registry was created after the establishment of
      laws promoting the development of clinical guidelines for diagnosis, management,
      census and registry of patients suffering rare diseases. RESULTS: In total,
      13,215 patients were recorded in the Colombian registry. The survey reported 653
      rare diseases. The most common diseases were congenital factor VIII deficiency
      (hemophilia A) (8.5%), myasthenia gravis (6.4%), von Willebrand disease (5.9%),
      short stature due to growth hormone qualitative anomaly (4.2%), bronchopulmonary
      dysplasia (3.9%) and cystic fibrosis (3.2%). Although, a marked under-reporting
      of cases was observed, some pathologies displayed similar behavior to that
      reported by other initiatives and databases. The data currently available in the
      registry provides a baseline for improvement regarding local and regional surveys
      and the start for better understanding rare diseases in Colombia.

PMID- 29073919
TI  - A review of virulent Newcastle disease viruses in the United States and the role
      of wild birds in viral persistence and spread.
AB  - Newcastle disease is caused by virulent strains of Newcastle disease virus (NDV),
      which causes substantial morbidity and mortality events worldwide in poultry. The
      virus strains can be differentiated as lentogenic, mesogenic, or velogenic based
      on a mean death time in chicken embryos. Currently, velogenic strains of NDV are
      not endemic in United States domestic poultry; however, these strains are present
      in other countries and are occasionally detected in wild birds in the U.S. A
      viral introduction into domestic poultry could have severe economic consequences
      due to the loss of production from sick and dying birds, the cost of control
      measures such as depopulation and disinfection measures, and the trade
      restrictions that would likely be imposed as a result of an outbreak. Due to the
      disease-free status of the U.S. and the high cost of a potential viral incursion
      to the poultry industry, a qualitative risk analysis was performed to evaluate
      the vulnerabilities of the U.S. against the introduction of virulent strains of
      NDV. The most likely routes of virus introduction are explored and data gathered
      by several federal agencies is provided. Recommendations are ultimately provided
      for data that would be useful to further understand NDV on the landscape and to
      utilize all existing sampling opportunities to begin to comprehend viral movement
      and further characterize the risk of NDV introduction into the U.S.

PMID- 29073921
TI  - Acceptability of smartphone text- and voice-based ecological momentary assessment
      (EMA) methods among low income housing residents in New York City.
AB  - OBJECTIVES: This study aimed to evaluate the acceptability of smartphone-based
      text message- and voice-based ecological momentary assessment (EMA) methods among
      a sample of low-income housing residents in New York City. Using data from the
      community-based NYC Low Income Housing, Neighborhoods and Health Study (n = 112),
      the acceptability of text message- and voice-based EMA methods were assessed via
      survey. RESULTS: Overall, 88.4% of participants reported that they would
      participate in a study that utilized text message-based EMA. These analyses
      showed no appreciable differences by sub-groups (p > .05). Overall, 80.2% of
      participants reported that they would participate in a study that used voice
      based EMA. This voice-based method was least acceptable among participants
      younger than 25 years old compared to participants of all other ages, chi2(2) =
      10.107, p = .006 (among the younger participants 60.7% reported "yes" regarding
      the anticipated acceptability of voice-based EMA and 39.3% reported "no").
      Overall, this work suggests that text message- and voice-based EMA methods are
      acceptable for use among low-income housing residents. However, the association
      between age and the acceptability of voice-based EMA suggests that these methods
      may be less suited for younger populations.

PMID- 29073920
TI  - Homeostatic modulation on unconscious hedonic responses to food.
AB  - OBJECTIVE: Hedonic/affective responses to food play a critical role in eating
      behavior. Previous behavioral studies have shown that hedonic responses to food
      are elicited consciously and unconsciously. Although the studies also showed that
      hunger and satiation have a modulatory effect on conscious hedonic responses to
      food, the effect of these homeostatic states on unconscious hedonic responses to
      food remains unknown. RESULTS: We investigated unconscious hedonic responses to
      food in hungry and satiated participants using the subliminal affective priming
      paradigm. Food images or corresponding mosaic images were presented in the left
      or right peripheral visual field during 33 ms. Then photographs of target faces
      with emotionally neutral expressions were presented, and the participants
      evaluated their preference for the faces. Additionally, daily eating behaviors
      were assessed using questionnaires. Preference for the target faces was increased
      by food images relative to the mosaics in the hungry, but not the satiated,
      state. The difference in preference ratings between the food and mosaic
      conditions was positively correlated with the tendency for external eating in the
      hungry, but not the satiated, group. Our findings suggest that homeostatic states
      modulate unconscious hedonic responses to food and that this phenomenon is
      related to daily eating behaviors.

PMID- 29073922
TI  - Mimicking hypersensitivity pneumonitis as an uncommon initial presentation of
      chronic granulomatous disease in children.
AB  - Dry cough, dyspenea and diffuse centrilobular nodules in both lungs of radiologic
      findings similar to hypersensitivity pneumonitis (HP) are rare initial
      presentation in chronic granulomatous disease (CGD). CGD is remarkable for
      increased susceptibility to bacterial and fungal infections as well as high
      sensitivity to inciting antigens such as Aspergillus species due to dysregulated
      inflammation. We identified three children who had an initial presentation
      mimicking HP and were subsequently diagnosed as CGD. All patients developed
      invasive pulmonary A. fumigatus infection (IPAI) following systemic
      glucocorticoid therapy. Two of the three patients were found to have mutations in
      NCF1 gene and one patient in NCF2 gene. As HP is uncommon in children, we should
      consider the possibility of CGD in children with HP, even in mimicking HP
      patients with suggestive inhalation history and negative fungal cultures. A
      prompt diagnosis of CGD is essential to enable initiation of prophylactic
      antibacterial and antifungal therapies.

PMID- 29073923
TI  - Achieving community-based postpartum follow up in eastern Uganda: the field
      experience from the MamaMiso Study on antenatal distribution of misoprostol.
AB  - BACKGROUND: Advance provision of misoprostol to women during antenatal care aims
      to achieve broader access to uterotonics for the prevention of postpartum
      hemorrhage. Studies of this community-based approach usually involve antenatal
      education as well as timely postpartum follow-up visits to confirm maternal and
      neonatal outcomes. The MamaMiso study in Mbale, Uganda sought to assess the
      feasibility of conducting follow-up visits in the postpartum period following
      advance provision of misoprostol for postpartum hemorrhage prevention. MamaMiso
      recruited women during antenatal care visits. Participants were asked to contact
      the research team within 48 h of giving birth so that postpartum follow-up visits
      could be carried out at their homes. Women's baseline and delivery
      characteristics were collected and analyzed with respect to follow-up time ('on
      time' <= 7 days, 'late' > 7 days, and 'lost to follow up'). Every woman who was
      followed up late due to a failure to report the delivery was asked for the
      underlying reasons for the delay. When attempts at following up participants were
      unsuccessful, a file note was generated explaining the details of the failure. We
      abstracted data and identified themes from these notes. RESULTS: Of 748 recruited
      women, 700 (94%) were successfully followed up during the study period, 465 (62%)
      within the first week postpartum. The median time to follow up was 4 days and was
      similar for women who delivered at home or in facilities and for women who had
      attended or unattended births. Women recruited at the urban hospital site (as
      opposed to rural health clinics) were more likely to be lost to follow up or
      followed up late. Of the women followed up late, 202 provided a reason. File
      notes explaining failed attempts at follow up were generated for 164
      participants. Several themes emerged from qualitative analysis of these notes
      including phone difficulties, inaccurate baseline information, misperceptions,
      postpartum travel, and the condition of the mother and neonate. CONCLUSIONS:
      Keeping women connected to the health system in the postpartum period is
      feasible, though reaching them within the first week of their delivery is
      challenging. Understanding characteristics of women who are harder to reach can
      help tailor follow-up efforts and elucidate possible biases in postpartum study
      data. Trial Registration Number ISRCTN70408620 December 28, 2011.

PMID- 29073924
TI  - Home-based preoperative rehabilitation (prehab) to improve physical function and
      reduce hospital length of stay for frail patients undergoing coronary artery
      bypass graft and valve surgery.
AB  - BACKGROUND: Evidence suggests that elective cardiac patients are at risk of
      functional and psychological deterioration in the time preceding surgery. This
      poses a risk to successful post-operative rehabilitation. This prospective one
      group pre-test, post-test evaluation was designed to assess a clinical Pre
      operative Rehabilitation (PREHAB) home-based exercise programme, to optimise pre
      operative physical function and frailty in patients awaiting elective Coronary
      Artery By-Pass Graft (CABG) or Valve Surgery. METHOD: Consenting patients
      awaiting cardiac surgery, with wait time >= 6 weeks were referred to a Senior
      Physiotherapist for baseline assessment. Patients were offered PREHAB in the form
      of functional home-based exercise that was prescribed from baseline physical
      outcomes. All patients were followed up via telephone to ensure progression of
      exercise and any problems associated with it. This continued weekly until the
      patient attended Surgical Pre-assessment clinic, where all outcome measures were
      re-assessed. RESULTS: Twenty two patients, out of a total number of 36 patients
      seen in the surgical clinic between March 2016 and August 2016, participated in
      the prehab clinical evaluation. Twenty patients completed their prescribed
      exercises on a weekly basis prior to surgery. No adverse events or cardiac
      symptoms were reported as a result of the home exercise intervention. Paired t
      Test analyses revealed a significant mean difference in clinical frailty score
      (CFS) of -0.53 +/- 0.51 (95% CI [-0.774, -0.279], P = 0.0003). Significant mean
      difference in six-minute walk test (6MWT) distance of 42.5 +/- 27.8 m (95% CI
      [23.840, 61.251], P = 0.0005), 6MWT walking speed of 0.5 +/- 0.4kmh (95% CI,
      [0.2433, 0.7567], P = 0.001), and short physical performance battery (SPPB) total
      score of 2.2 +/- 1.7, (95% CI [3.066, 1.200], P = 0.0002) were also observed. The
      change in 6MWT distance was shown to be significantly associated with hospital
      length of stay (LOS) (r = 0.7; P = 0.03). CONCLUSION: This small exploratory
      evaluation suggests that providing a home-based PREHAB programme for frail
      patients undergoing CABG or Valve surgery may be able to improve functional
      ability and reduce hospital length of stay for those patients undergoing cardiac
      surgery. A frailty score with greater sensitivity may be required to elucidate
      the influence frailty could have in reducing length of stay. A large randomised
      controlled study is required to reveal the potential beneficial effects of PREHAB
      in this patient population.

PMID- 29073925
TI  - Prevalence of overweight and obesity among type 2 diabetic patients attending
      diabetes clinics in northern Tanzania.
AB  - OBJECTIVES: To determine the prevalence of overweight and obesity among patients
      with type 2 diabetes who are attending diabetes clinics in northern Tanzania.
      RESULTS: In total 227 type 2 diabetic patients attending diabetes clinics were
      enrolled. Majority of patients 193 (85.0%) were overweight (44.9%) or obese
      (40.1%). Of them, 65 (33.7%) were overweight/obese after diagnosis of type 2
      diabetes. The prevalence of overweight/obesity was significantly higher in female
      participants than the males [92.2% vs. 69.2%; OR = 5.10; 95% CI 2.22-11.05].
      Regarding the region of residence, Kilimanjaro (100.0%) and Arusha (89.8%)
      regions had significantly highest prevalence of overweight/obesity compared to
      Tanga region (69.2%) [chi2 = 32.455, P < 0.001].

PMID- 29073926
TI  - Propranolol in the preoperative treatment of Kasabach-Merritt syndrome: a case
      report.
AB  - BACKGROUND: Kasabach-Merritt syndrome represents the association of hemangioma
      with thrombocytopenia and consumptive coagulopathy. We present a case of Kasabach
      Merritt syndrome treatment with orally administered propranolol. CASE
      PRESENTATION: A 4.5-month-old caucasian female infant with congenital giant
      hemangioma in the posterior region of her neck presented to our Institute for
      Childhood Diseases where she underwent clinical, laboratory, and radiological
      investigations. A low blood platelet count indicated the use of corticosteroids
      and blood components as first-line therapy. The lack of therapeutic response
      induced the introduction of orally administered propranolol as additive therapy.
      A 3-week treatment led to a reduction in the size of hemangioma and a rise in
      platelet count which enabled surgical treatment and definite healing. CONCLUSION:
      Orally administered propranolol as monotherapy or in combination with other
      therapeutic modalities may play a key role in the treatment of Kasabach-Merritt
      syndrome.

PMID- 29073927
TI  - Arcanobacterium phocae infection in mink (Neovison vison), seals (Phoca vitulina,
      Halichoerus grypus) and otters (Lutra lutra).
AB  - BACKGROUND: Infectious skin disorders are not uncommon in mink. Such disorders
      are important as they have a negative impact on animal health and welfare as well
      as on the quality and value of the fur. This study presents the isolation of
      Arcanobacterium phocae from mink with severe skin lesions and other pathological
      conditions, and from wild seals and otters. RESULTS: In 2015, A. phocae was
      isolated for the first time in Denmark from outbreaks of dermatitis in mink
      farms. The outbreaks affected at least 12 farms. Originating from these 12 farms,
      23 animals cultured positive for A. phocae. The main clinical findings were
      necrotizing pododermatitis or dermatitis located to other body sites, such as the
      lumbar and cervical regions. A. phocae could be isolated from skin lesions and in
      nine animals also from liver, spleen and lung, indicating a systemic spread. The
      bacterium was also, for the first time in Denmark, detected in dead seals (n = 9)
      (lungs, throat or wounds) and otters (n = 2) (throat and foot). CONCLUSIONS: An
      infectious skin disorder in mink associated with A. phocae has started to occur
      in Danish farmed mink. The origin of the infection has not been identified and it
      is still not clear what the pathogenesis or the port of entry for A. phocae
      infections are.

PMID- 29073928
TI  - Safety of tubal ligation by minilaparotomy provided by clinical officers versus
      assistant medical officers: study protocol for a noninferiority randomized
      controlled trial in Tanzanian women.
AB  - BACKGROUND: Female sterilization by tubal ligation is a safe, extremely
      effective, and permanent way to limit childbearing. It is the most popular modern
      contraceptive method worldwide. The simplest way to provide tubal ligation is by
      a procedure called minilaparotomy, generally performed with the client under
      local anesthesia with systemic sedation and analgesia. In Tanzania, unmet need
      for family planning is high and has declined little in the past decade. Access to
      tubal ligation is limited throughout the country, in large part because of a lack
      of trained providers. Clinical officers (COs) are midlevel health workers who
      provide diagnosis, treatment, and minor surgeries. They are more prevalent than
      physicians in poorer and rural communities. Task shifting-the delegation of some
      tasks to less-specialized health workers, including task shifting of surgical
      procedures to midlevel cadres-has improved access to lifesaving interventions in
      resource-limited settings. It is a cost-effective way to address shortages of
      physicians, increasing access to services. The primary objective of this trial is
      to establish whether the safety of tubal ligation by minilaparotomy provided by
      COs is noninferior to the safety of tubal ligation by minilaparotomy provided by
      physicians (assistant medical officers [AMOs]), as measured by rates of major
      adverse events (AEs) during the procedure and through 42 days of follow-up.
      METHODS/DESIGN: In this facility-based, multicenter, noninferiority randomized
      controlled trial, we are comparing the safety of tubal ligation by minilaparotomy
      performed by trained COs versus by trained AMOs. The primary outcome is safety,
      defined by the overall rate of major AEs occurring during the minilaparotomy
      procedure and through 42 days of follow-up. The trial will be conducted among
      1970 women 18 years of age or older presenting for tubal ligation at 7 study
      sites in northern Tanzania. DISCUSSION: If no major safety issues are identified,
      the data from this trial may facilitate changes in the Tanzanian government's
      regulations, allowing appropriately trained COs to provide tubal ligation by
      minilaparotomy. Positive findings may have broader implications. Task shifting to
      provide long-acting contraceptives, if proven safe, may be an effective approach
      to increasing contraceptive access in low- and middle-income countries. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02944149 . Registered on 14 October 2016.

PMID- 29073929
TI  - Health-related quality of life of mothers of children with congenital heart
      disease in a sub-Saharan setting: cross-sectional comparative study.
AB  - BACKGROUND: While the Health Related Quality of Life of the children with
      congenital heart defects is primarily affected, caring for a child with birth
      defect has an impact on the family's quality of life as well. Understanding the
      level of quality of life of the parents, which is likely to vary in different
      cultural settings, beliefs and parental educational status may help to implement
      educational programs and other interventional measures that may improve the HRQOL
      of parents of such children. This cross-sectional comparative study reports the
      health-related quality of life of mothers of children with congenital heart
      diseases in a sub-Saharan setting. RESULTS: Mean age of the mothers in the study
      group was 32.2 +/- 7.1 years where as that of the control group was 30.5 +/- 6.5
      years (p = .054). One hundred-four children had congenital cardiac lesions
      classified as mild to moderate while 31 patients had severe lesions. On average,
      mothers in the study group showed poor performance on the Short Form-36 (SF-36)
      with statistically significant differences on all sub-scales including general
      health perception, physical functioning, role physical, role emotional, social
      functioning, bodily pain, vitality and mental health. Severity of the congenital
      heart defect was not associated with statistically significant difference in the
      health-related quality of life of the mothers. CONCLUSIONS: Mothers of children
      with congenital heart disease in our study have significantly lower quality of
      life in all domains of SF-36 compared to the control group. Planning and devising
      a strategy to support these mothers may need to be part of management and
      clinical care of children with congenital heart diseases.

PMID- 29073930
TI  - Functional evaluation of sublingual microcirculation indicates successful weaning
      from VA-ECMO in cardiogenic shock.
AB  - BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is
      increasingly adopted for the treatment of cardiogenic shock (CS). However, a
      marker of successful weaning remains largely unknown. Our hypothesis was that
      successful weaning is associated with sustained microcirculatory function during
      ECMO flow reduction. Therefore, we sought to test the usefulness of
      microcirculatory imaging in the same sublingual spot, using incident dark field
      (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF
      imaging with echocardiographic parameters. METHODS: Weaning was performed by
      decreasing the VA-ECMO flow to 50% (F50) from the baseline. The endpoint of the
      study was successful VA-ECMO explantation within 48 hours after weaning. The
      response of sublingual microcirculation to a weaning attempt (WA) was evaluated.
      Microcirculation was measured in one sublingual area (single spot (ss)) using
      CytoCam IDF imaging during WA. Total vessel density (TVDss) and perfused vessel
      density (PVDss) of the sublingual area were evaluated before and during 50% flow
      reduction (TVDssF50, PVDssF50) after a WA and compared to conventional
      echocardiographic parameters as indicators of the success or failure of the WA.
      RESULTS: Patients (n = 13) aged 49 +/- 18 years, who received VA-ECMO for the
      treatment of refractory CS due to pulmonary embolism (n = 5), post cardiotomy (n
      = 3), acute coronary syndrome (n = 2), myocarditis (n = 2) and drug intoxication
      (n = 1), were included. TVDssF50 (21.9 vs 12.9 mm/mm2, p = 0.001), PVDssF50 (19.7
      vs 12.4 mm/mm2, p = 0.01) and aortic velocity-time integral (VTI) at 50% flow
      reduction (VTIF50) were higher in patients successfully weaned vs not
      successfully weaned. The area under the curve (AUC) was 0.99 vs 0.93 vs 0.85 for
      TVDssF50 (small vessels) >12.2 mm/mm2, left ventricular ejection fraction (LVEF)
      >15% and aortic VTI >11 cm. Likewise, the AUC was 0.91 vs 0.93 vs 0.85 for the
      PVDssF50 (all vessels) >14.8 mm/mm2, LVEF >15% and aortic VTI >11 cm. CONCLUSION:
      This study identified sublingual microcirculation as a novel potential marker for
      identifying successful weaning from VA-ECMO. Sustained values of TVDssF50 and
      PVDssF50 were found to be specific and sensitive indicators of successful weaning
      from VA-ECMO as compared to echocardiographic parameters.

PMID- 29073931
TI  - scDual-Seq: mapping the gene regulatory program of Salmonella infection by host
      and pathogen single-cell RNA-sequencing.
AB  - The interaction between a pathogen and a host is a highly dynamic process in
      which both agents activate complex programs. Here, we introduce a single-cell RNA
      sequencing method, scDual-Seq, that simultaneously captures both host and
      pathogen transcriptomes. We use it to study the process of infection of
      individual mouse macrophages with the intracellular pathogen Salmonella
      typhimurium. Among the infected macrophages, we find three subpopulations and we
      show evidence for a linear progression through these subpopulations, supporting a
      model in which these three states correspond to consecutive stages of infection.

PMID- 29073932
TI  - Factors affecting the self-rated health of elderly individuals living alone: a
      cross-sectional study.
AB  - OBJECTIVE: In Japan, the number of elderly individuals living alone is continuing
      to increase as society ages. Although studies have considered quality of life,
      life expectancy, and gender differences in elderly individuals living alone, only
      a few have considered the health and lifestyle of these individuals. Therefore,
      we aimed to investigate the factors that affect the self-rated health of elderly
      individuals living alone to understand this group and how best to offer them
      support. RESULTS: We include 113 individuals. There was a significant difference
      (P < 0.05) in some characteristics (e.g., age, chronic illness, frequency of
      hospital visits in 1 month, and caregivers), activities of daily living (e.g.,
      motor tasks), and instrumental activities of daily living (e.g., household
      affairs, heavy housework, outdoor household, and outdoor activities).

PMID- 29073934
TI  - Noninvasive ventilation in hypercapnic chronic obstructive pulmonary disease.

PMID- 29073933
TI  - Role of tumor suppressor p53 and micro-RNA interplay in multiple myeloma
      pathogenesis.
AB  - The molecular mechanisms underlying dysregulated wild type (wt) p53 in multiple
      myeloma (MM) have been subjects of intense investigation for years. Indeed,
      correlation of rarely occurring TP53 gene mutations or deletions with adverse
      clinical outcomes in MM patients is strongly established, while in majority of
      cases wtp53 seems to be non-functional or dysregulated bearing a high clinical
      impact. Interestingly, findings from recent investigations show that micro-RNAs
      (miRNAs) may contribute to suppression of wtp53 in MM, as they are now known to
      function as key regulatory elements in the p53 network. This area is shedding new
      light on understanding the biologic effects of dysregulated p53 in MM
      pathogenesis especially drug resistance. miRNAs such as miR-125b (oncomiR) or miR
      34a (tumor suppressor-miR) can be negative or positive regulators of wtp53
      function, respectively, with specific effects on MM cell viability. On the other
      hand, our knowledge of miRNA interaction with mutant (mt) p53 in MM, which is
      rather related to disease progression and resistance to therapy, is limited which
      demands in-depth exploration. Here, we will put forward the current knowledge on
      miRNA-p53 interaction in MM and its role in MM pathogenesis including drug
      resistance. We will also highlight the pre-clinical approaches for therapeutic
      application of miRNAs targeting p53 pathway.

PMID- 29073936
TI  - Evaluation of the efficacy of a commercial inactivated genogroup 2b-based porcine
      epidemic diarrhea virus (PEDV) vaccine and experimental live genogroup 1b
      exposure against 2b challenge.
AB  - Porcine epidemic diarrhea virus strains from the G1b cluster are considered less
      pathogenic compared to the G2b cluster. The aim of this study was to compare the
      ability of G1b-based live virus exposure against use of a commercial G2b-based
      inactivated vaccine to protect growing pigs against G2b challenge. Thirty-nine
      PEDV naive pigs were randomly divided into five groups: EXP-IM-1b (intramuscular
      G1b exposure; G2b challenge), EXP-ORAL-1b (oral G1b exposure; G2b challenge), VAC
      IM-2b (intramuscular commercial inactivated G2b vaccination; G2b challenge), POS
      CONTROL (sham-vaccination; G2b challenge) and NEG-CONTROL (sham-vaccination; sham
      challenge). Pigs were vaccinated/exposed at 3 weeks of age (day post-vaccination
      0, dpv 0), VAC-IM-2b pigs were revaccinated at dpv 14, and the pigs were
      challenged at dpv 28. Among all groups, VAC-IM-2b pigs had significantly higher
      anti-PEDV IgG levels on dpv 21 and 28 while EXP-ORAL-1b pigs had significantly
      higher anti-PEDV IgA levels on dpv 14, 21, 28 and 35. EXP-ORAL-1b also had
      detectable IgA in feces. Intramuscular PEDV exposure did not result in a
      detectable antibody response in EXP-IM-1b pigs. The fecal PEDV RNA levels in VAC
      IM-2b pigs were significantly lower 5-7 days after challenge compared to the POS
      CONTROL group. Under the study conditions a commercial inactivated G2b-based
      vaccine protected pigs against G2b challenge, as evidenced by reduction of PEDV
      RNA in feces for 3-4 logs during peak shedding and a shorter viral shedding
      duration. The oral, but not the intramuscular, experimental G1b-based live virus
      exposure induced a high anti-PEDV IgA response prior to challenge, which
      apparently did not impact PEDV shedding compared to POS-CONTROL pigs.

PMID- 29073937
TI  - Tumoral calcinosis in the cervical spine: a case report and review of the
      literature.
AB  - BACKGROUND: Tumoral calcinosis is rarely located in spine. A 55-year-old Japanese
      woman with cervical tumoral calcinosis is presented, along with a review of the
      literature relating to tumoral calcinosis in the spine. We discussed the
      etiology, diagnosis, and management of this condition. CASE PRESENTATION: We
      report a case of a patient with cervical tumoral calcinosis with end-stage renal
      disease. A computed tomography scan showed a lobulated, calcified mass around the
      right facet joint at the fourth-fifth cervical spine and calcifications were also
      observed in the right intervertebral foramens at fourth-fifth cervical spine and
      fifth-sixth cervical spine levels and the anterior wall of the spinal canal. By
      performing a cervical decompression and stabilization, the patient recovered from
      her neurological symptoms. CONCLUSIONS: Although tumoral calcinosis is rarely
      located in the spine, it should be considered in the differential diagnosis of
      spinal lesions. If a calcified mass causes acute neurological symptoms, resection
      of the mass is still the most important treatment.

PMID- 29073935
TI  - Human health implications of organic food and organic agriculture: a
      comprehensive review.
AB  - This review summarises existing evidence on the impact of organic food on human
      health. It compares organic vs. conventional food production with respect to
      parameters important to human health and discusses the potential impact of
      organic management practices with an emphasis on EU conditions. Organic food
      consumption may reduce the risk of allergic disease and of overweight and
      obesity, but the evidence is not conclusive due to likely residual confounding,
      as consumers of organic food tend to have healthier lifestyles overall. However,
      animal experiments suggest that identically composed feed from organic or
      conventional production impacts in different ways on growth and development. In
      organic agriculture, the use of pesticides is restricted, while residues in
      conventional fruits and vegetables constitute the main source of human pesticide
      exposures. Epidemiological studies have reported adverse effects of certain
      pesticides on children's cognitive development at current levels of exposure, but
      these data have so far not been applied in formal risk assessments of individual
      pesticides. Differences in the composition between organic and conventional crops
      are limited, such as a modestly higher content of phenolic compounds in organic
      fruit and vegetables, and likely also a lower content of cadmium in organic
      cereal crops. Organic dairy products, and perhaps also meats, have a higher
      content of omega-3 fatty acids compared to conventional products. However, these
      differences are likely of marginal nutritional significance. Of greater concern
      is the prevalent use of antibiotics in conventional animal production as a key
      driver of antibiotic resistance in society; antibiotic use is less intensive in
      organic production. Overall, this review emphasises several documented and likely
      human health benefits associated with organic food production, and application of
      such production methods is likely to be beneficial within conventional
      agriculture, e.g., in integrated pest management.

PMID- 29073938
TI  - Musashi-2, a novel oncoprotein promoting cervical cancer cell growth and
      invasion, is negatively regulated by p53-induced miR-143 and miR-107 activation.
AB  - BACKGROUND: Although previous studies have shown promise for targeting Musashi
      RNA-binding protein 2 (MSI-2) in diverse tumors, the role and mechanism of MSI-2
      for cervical cancer (CC) progression and the regulation of MSI-2 expression
      remains unclear. METHODS: Using gene expression and bioinformatic analysis,
      together with gain- and loss-of-function assays, we identified MSI-2 as a novel
      oncogenic driver and a poor prognostic marker in CC. We explored the regulation
      of c-FOS by MSI-2 via RNA-immunoprecipitation and luciferase assay, and confirmed
      a direct inhibition of MSI-2 by miR-143/miR-107 using luciferase assay. We
      assessed the effect of a natural antibiotic Mithramycin A on p53, miR-143/miR-107
      and MSI-2 expression in CC cells. RESULTS: MSI-2 mRNA is highly expressed in CC
      tissues and its overexpression correlates with lower overall survival. MSI-2
      promotes CC cell growth, invasiveness and sphere formation through directly
      binding to c-FOS mRNA and by increasing c-FOS protein expression. Furthermore,
      miR-143/miR-107 are two tumor suppressor miRNAs that directly bind and inhibit
      MSI-2 expression in CC cells, and downregulation of miR-143/miR-107 associates
      with poor patient prognosis. Importantly, we found that p53 decreases the
      expression of MSI-2 through elevating miR-143/miR-107 levels, and treatment with
      a natural antibiotic Mithramycin A increased p53 and miR-143/miR-107 expression
      and reduced MSI-2 expression, resulting in the inhibition of CC cell
      proliferation, invasion and sphere formation. CONCLUSIONS: These results suggest
      that MSI-2 plays a crucial role in promoting the aggressive phenotypes of CC
      cells, and restoration of miR-143/miR-107 by Mithramycin A via activation of p53
      may represent a novel therapeutic approach for CC.

PMID- 29073939
TI  - A comparison of decisions to discharge committed psychiatric patients between
      treating physicians and district psychiatric committees: an outcome study.
AB  - BACKGROUND: The Israel Mental Health Act of 1991 stipulates a process for
      involuntary psychiatric hospitalization (IPH). A patient thus hospitalized may be
      discharged by either the treating psychiatrist (TP) or the district psychiatric
      committee (DPC). The decision rendered by the DPC is often at odds with the
      recommendation of the TP. Although much has been written about the ethical issues
      of restricting patients' rights and limiting their freedom, far less attention
      has been devoted to the psychiatric, medical, and social outcome of legal patient
      discharge against the doctor's recommendation. METHODS: In our study we examined
      the outcomes of the decisions made by the DPC using readmission data, an
      internationally recognized indicator of the quality of hospital care, and
      compared them to the outcomes of patients discharged by the TP. All IPH
      discharges resulting from the DPC's determination for the year 2013 (N = 972)
      were extracted from the Israel national register. We also collected all IPH
      discharges owing to the TP's decision for 2013 (N = 5788). We defined "failure"
      as readmission in less than 30 days, involuntary civil readmission in less than
      180 days, and involuntary readmission under court order in less than 1 year.
      RESULTS: The rehospitalization pattern was compared in the two groups of patients
      discharged from their psychiatric hospitalization during 2013 (index discharges)
      and followed up individually for a year. We found a statistically significant
      difference between the DPC and the TP group for each of the time frames, with the
      DPC group returning to IPH much more frequently than the TP group. Using cross
      sectional comparison with logistic regression adjusted for age, gender, diagnosis
      and length of hospitalization, we found the probability of a decision failure in
      the TP group was significantly less with an OR of 0.7 (95% CI .586-.863),
      representing a 30% adjusted decrease in the probability for failure in the TP
      group. CONCLUSIONS: The results we present show that the probability of decision
      "failure" (readmission) was found to be significantly higher in the DPC group
      than in the TP group. It is often assumed that IPH patients will fare better at
      home in their communities than in a protracted hospitalization. This is
      frequently the rationale for early discharge by the DPC (30.1 days vs. 75.9 DPC
      and TP groups, respectively). Our results demonstrate that this rationale may
      well be a faulty generalization.

PMID- 29073940
TI  - Practices regarding human Papillomavirus counseling and vaccination in head and
      neck cancer: a Canadian physician questionnaire.
AB  - BACKGROUND: Human papillomavirus (HPV) has recently been implicated as a
      causative agent in a rapidly growing number of oropharyngeal cancers. Emerging
      literature supports the hypothesis that HPV vaccination may protect against HPV
      related head and neck cancer (HNC) in addition to HPV-related cervical and
      anogenital disease. While the association between HPV infection and cervical
      cancer is widely understood, its relation to HNC is less well known. The purpose
      of this study was to better understand HPV counseling practices for infection and
      vaccination in relation to HNC of primary care physicians (PCPs),
      Obstetricians/Gynecologists (OBGYNs), and Otolaryngology - Head and Neck Surgeons
      (OHNSs) in Canada. METHODS: A Canada-wide electronic questionnaire regarding
      counseling practices on HPV infection, transmission, and vaccination was designed
      and distributed to PCPs, OBGYNs, and OHNSs across Canada through electronic and
      paper-based methods. Basic Descriptive statistics were used to analyze responses.
      RESULTS: In total, 337 physicians responded (239 family physicians, 51 OHNSs, 30
      OBGYNs, and 17 pediatricians). Three out of four PCPs reported routine counseling
      of their patients regarding HPV infection, transmission, and vaccination. Among
      this group, 68% reported "never" or "rarely" counseling patients that HPV can
      cause HNC. The most commonly reported reason that PCPs cited for not counseling
      was a lack of knowledge. The majority of OHNSs (81%) and OBGYNs (97%) counseled
      patients regarding HPV infection, transmission, and vaccination. However, very
      few OHNSs (10%) regularly counseled patients with HPV-related HNC about HPV
      related anogenital cancer. Similarly, very few OBGYNs (18%) regularly counseled
      patients with HPV related cervical/anogenital cancer about HPV related HNC.
      CONCLUSIONS: The rate of counseling on HPV infection, transmission, and
      vaccination in relation to HNC among PCPs is low. The most common reason is a
      lack of knowledge. Specialists rarely counsel patients with confirmed HPV-related
      cancer about other HPV-related malignancies. More research is needed on the
      relationship between different HPV-related cancers in order to better inform
      counseling practices.

PMID- 29073941
TI  - A comparison of unheated loose housing with stables on the respiratory health of
      weaned-foals in cold winter conditions: an observational field-study.
AB  - BACKGROUND: Newly weaned horses in Finland are often moved to unheated loose
      housing systems in which the weanlings have free access to a paddock and a
      shelter. This practice is considered to be good for the development of young
      horses. The daily temperatures can stay below - 20  degrees C in Finland for
      several consecutive weeks during the winter season. However, the effect of
      unheated housing in a cold climatic environment on the respiratory health of
      weanlings under field conditions has not been studied before. This investigation
      was an observational field-study comprising 60 weanlings among 11 different
      voluntary participant rearing farms in Finland. Weanlings were either kept in
      unheated loose housing systems (n = 36) or in stables (n = 24) and were
      clinically examined on two separate occasions 58 days apart in cold winter
      conditions. RESULTS: The odds of clinical respiratory disease were lower in the
      older foals (loge days); OR = 0.009, P = 0.044). The plasma fibrinogen
      concentration was higher when the available space (m2/weanling) in the sleeping
      hall was smaller (P = 0.014) and it was lower when the sleeping hall was not
      insulated (P = 0.010). The plasma fibrinogen concentrations at the second
      examination were lower with a body condition score above 3 (P = 0.070).
      Standardbreds kept in loose housing systems had a lower body condition score than
      Finnhorses or Standardbreds kept in stables at both examinations (P = 0.026 and P
      = 0.007, respectively). Haemoglobin level was lower in weanlings in loose housing
      systems compared to their counterparts at the first examination (P = 0.037).
      Finnhorses had higher white blood cell count than Standardbreds at first (P =
      0.002) and at the second examination (P = 0.001). CONCLUSIONS: Keeping weanling
      horses in cold loose housing systems does not seem to increase the occurrence of
      respiratory disease, but special attention should be focused on ventilation, air
      quality and feeding-practices. Our field study data suggest it might be
      advantageous to keep Standardbred foals born late in the season in a stable over
      the Finnish winter.

PMID- 29073942
TI  - Relationship between Toll-like receptor 4 and type-2 diabetes mellitus
      complicated by tuberculosis.
AB  - OBJECTIVE: To investigate the association between single-nucleotide polymorphisms
      (SNPs) in the Toll-like receptor 4 (TLR4) gene (TLR4) and the relationship
      between SNPs and type-2 diabetes mellitus (T2DM) complicated by tuberculosis (TB)
      (T2DMTB) susceptibility. METHODS: The relationship between SNPs and T2DMTB was
      assessed using SNPstats (<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext
      link-type="uri"
      xlink:href="http://bioinfo.iconcologia.net/SNPstats">http://bioinfo.iconcologia.n
      t/SNPstats</ext-link>). Generalised multifactor dimensionality reduction (GMDR)
      was used to select the best interaction combination of the four SNPs. Stratified
      analysis was performed using logistic regression. RESULTS: Logistic analysis
      showed that both rs11536889 and rs7873784 in TLR4 were associated with risk of
      T2DMTB in additive and dominant models. Carriers with homozygous and heterozygous
      mutants of rs11536889 and rs7873784 were associated with higher T2DMTB risk than
      those with wild-type homozygotes (OR 1.68, 95%CI 1.22-2.17 and OR 1.61, 1.18
      2.09, respectively). GMDR analysis indicated a significant two-locus model (P =
      0.0107) involving rs7873784 and rs11536889; the cross-validation consistency of
      this model was 9/10, and testing accuracy was 60.11%. Participants with rs7873784
      GC/CC and rs11536889-GC/CC genotypes had the highest risk of T2DMTB compared with
      participants with rs7873784-GG and rs11536889-GG genotypes (OR 3.32, 95%CI 2.12
      4.63). CONCLUSIONS: We found that> rs11536889 and rs7873784 in the TLR4 gene, and
      their interactions, were associated with increased T2DMTB risk.

PMID- 29073944
TI  - Optimized QuEChERS Method Combined with UHPLC-MS/MS for the Simultaneous
      Determination of 15 Mycotoxins in Liquorice.
AB  - In our study, a reliable and rapid analytical method for the simultaneous
      determination of 15 mycotoxins (aflatoxin B1, aflatoxin B2, aflatoxin G1,
      aflatoxin G2, alternariol, agroclavine, citrinin, diacetoxyscirpenol,
      deoxynivalenol, fumonisin B1, fumonisin B2, ochratoxin A, sterigmatocystin, T-2
      toxin, and zearalenone) in liquorice using ultra-HPLC coupled to tandem MS was
      developed and validated. Due to the complex ingredients in liquorice, we chose a
      QuEChERS-based extraction procedure as the sample pretreatment. Meanwhile, for
      the first time, acetate buffer was used to replaced water, which can greatly
      reduce the concentration of formic acid in acetonitrile, which further reduces
      the extraction efficiency of impurities. The optimal combination of adsorbents is
      150 mg primary secondary amine, 150 mg silica gel, 600 mg octadecylsilane, and
      900 mg anhydrous magnesium sulfate. Electrospray ionization in both positive- and
      negative-ionization modes was applied to detect all the mycotoxins in a single
      run time of 15 min, with LOQs in the range of 0.125-2.5 MUg/kg. The recoveries of
      determination obtained were in the range of 81.0-104.7%, whereas the analytes
      could be accurately quantified in the 0.25-625 MUg/kg concentration range, with
      all coefficients being >0.992. Intra- and interday reproducibility were lower
      than 5.5 and 8.9%, respectively, for all analytical mycotoxins. The validated
      method was finally applied to screen mycotoxins in 31 batches of real samples
      collected from drugstores and hospitals in Shanghai, China. Our survey findings
      show that six mycotoxins were detected, including alternariol, citrinin,
      deoxynivalenol, fumonisin B1, ochratoxin, and zearalenone, and that the positive
      rate of mycotoxins was 54.8% in real samples, ranging from 3.37 to 520.6 MUg/kg.

PMID- 29073948
TI  - Long-Term Duration of Dual Antiplatelet Therapy: Patient Complexity Is More
      Important Than Lesion Complexity.

PMID- 29073947
TI  - Lesion Complexity and Outcomes of Extended Dual Antiplatelet Therapy After
      Percutaneous Coronary Intervention.
AB  - BACKGROUND: Subjects undergoing coronary stenting with complex lesion anatomy may
      experience different risks and benefits with prolonged dual antiplatelet therapy.
      OBJECTIVES: The authors assessed the effect of 30 months versus 12 months of dual
      antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) based
      on the presence or absence of anatomically-complex target lesions. METHODS: In
      the DAPT Study, combined myocardial infarction (MI) or stent thrombosis and
      moderate/severe bleeding were assessed in enrolled (n = 25,416) and randomized (n
      = 11,554) subjects. Complex lesions had any of the following characteristics:
      unprotected left main, >2 lesions/vessel, length >=30 mm, bifurcation with side
      branch >=2.5 mm, vein bypass graft, or thrombus-containing lesion. Events were
      evaluated according to increasing number of complexity characteristics and
      compared according to DAPT score. RESULTS: Enrolled subjects with more complex
      target lesions had higher rates of MI or stent thrombosis in the first 12 months
      after PCI (3.9% vs. 2.4%; p < 0.001). Among those who were event-free at 12
      months, rates of MI or stent thrombosis between 12 and 30 months were similar
      between those with versus without complex anatomy (3.5% vs. 2.9%; p = 0.07).
      Reduction of MI or stent thrombosis with continued thienopyridine beyond 12
      months versus placebo was similar for subjects with (2.5% vs. 4.5%; hazard ratio:
      0.55; 95% confidence interval: 0.38 to 0.79; p = 0.001) and without (2.0% vs.
      3.8%; hazard ratio: 0.52; 95% confidence interval: 0.39 to 0.69; p < 0.001)
      anatomic complexity (pinteraction = 0.81), as was increase in moderate/severe
      bleeding (pinteraction = 0.44). Among subjects with anatomic complexity, those
      with DAPT scores >=2 randomized to continued thienopyridine had greater
      reductions in MI or stent thrombosis (3.0% vs. 6.1%; p < 0.001) compared with
      subjects with scores <2 (1.7% vs. 2.3%; p = 0.42; p value comparing risk
      differences = 0.03). CONCLUSIONS: Complex target-lesion anatomy is associated
      with increased ischemic events, particularly within the first year after PCI.
      Among those without events in the first 12 months, the benefits of extending DAPT
      were similar in subjects with and without complex lesions. A high DAPT score
      identified those experiencing the most benefit from extended treatment among
      patients with and without complex anatomy. (The Dual Antiplatelet Therapy Study
      [DAPT Study]; NCT00977938).

PMID- 29073949
TI  - Stable High-Sensitivity Cardiac Troponin T Levels and Outcomes in Patients With
      Chest Pain.
AB  - BACKGROUND: There is a paucity of data on the association between high
      sensitivity cardiac troponin (hs-cTn) levels and outcomes in patients with chest
      pain but no myocardial infarction (MI), or any other condition that may lead to
      acutely elevated troponin levels. OBJECTIVES: The authors hypothesized that any
      detectable high-sensitivity cardiac troponin T (hs-cTnT) level is associated with
      adverse outcomes. METHODS: All patients (N = 22,589) >25 years of age with chest
      pain and hs-cTnT analyzed concurrently in the emergency department of Karolinska
      University Hospital, Stockholm, Sweden from 2011 to 2014 were eligible for
      inclusion. After excluding all patients with acute conditions that may have
      affected hs-cTnT, or MI associated with the visit, or insufficient information to
      determine whether troponin levels were stable, Cox regression was used to
      estimate risks for all-cause, cardiovascular, and noncardiovascular mortality,
      MI, and heart failure at different levels of troponins. RESULTS: A total of
      19,460 patients with a mean age of 54 +/- 17 years were included. During a mean
      follow-up of 3.3 +/- 1.2 years, 1,349 (6.9%) patients died. Adjusted hazard
      ratios (with 95% confidence intervals) for all-cause mortality were 2.00 (1.66 to
      2.42), 2.92 (2.38 to 3.59), 4.07 (3.28 to 5.05), 6.77 (5.22 to 8.78), and 9.68
      (7.18 to 13.00) in patients with hs-cTnT levels of 5 to 9, 10 to 14, 15 to 29, 30
      to 49, and >=50 ng/l, respectively, compared with patients with hs-cTnT levels <5
      ng/l. There was a strong and graded association between all detectable levels of
      hs-cTnT and risk for MI, heart failure, and cardiovascular and noncardiovascular
      mortality. CONCLUSIONS: Among patients with chest pain and stable troponin
      levels, any detectable level of hs-cTnT is associated with an increased risk of
      death and cardiovascular outcomes and should merit further attention.

PMID- 29073950
TI  - Time for a New Strategy for High-Sensitivity Troponin in the Emergency
      Department.

PMID- 29073952
TI  - HAART for Kids' Hearts: The Long View.

PMID- 29073951
TI  - Cardiac Effects of Highly Active Antiretroviral Therapy in Perinatally HIV
      Infected Children: The CHAART-2 Study.
AB  - BACKGROUND: Before the introduction of highly active antiretroviral therapy
      (HAART), cardiac mortality and morbidity were common in HIV-infected children.
      OBJECTIVES: This study sought to identify long-term cardiovascular effects of
      HAART in HIV-infected children. METHODS: The CHAART-2 (HAART-Associated
      Cardiotoxicity in HIV-Infected Children) study prospectively compared 148
      echocardiograms from 74 HAART-exposed children to 860 echocardiograms from 140
      HAART-unexposed but HIV-infected children from the Pulmonary and Cardiac
      Complications of Vertically Transmitted HIV Infection (P2C2 HIV) study. Both
      studies used similar protocol, centralized echocardiographic interpretation, and
      measures expressed as z-scores referenced to healthy controls. Associations
      between HAART exposure and echocardiographic measures were evaluated using
      generalized estimating equations. RESULTS: Comparing the HAART-exposed and HAART
      unexposed groups, any HAART exposure was positively associated with left
      ventricular (LV) fractional shortening (z-score for difference = 1.07; p = 0.02)
      and HAART exposure duration (z-score difference per year = 0.17; p = 0.003. LV
      mass was negatively associated with any HAART exposure (z-score difference = 
      0.64; p = 0.01) as was septal thickness (z-score difference = -0.93; p = 0.001).
      Duration of HAART exposure was negatively associated with LV end-systolic
      dimension and heart rate (z-score difference per year= -0.11; p = 0.05; and z
      score difference per year = -0.10; p = 0.002, respectively). During 11 years of
      follow-up, in the HAART-exposed group, LV mass and LV end-diastolic septal
      thickness were lower whereas LV contractility and LV fractional shortening were
      higher when compared to the HAART-unexposed group. CONCLUSIONS: Cardiac structure
      and function were better in perinatally HIV-infected children exposed to HAART
      than in those of similar children from the pre-HAART era but did decline over
      time. Evidence-based strategies for cardiovascular monitoring are needed to
      inform treatment decisions to improve long-term cardiovascular health.

PMID- 29073953
TI  - Temporary Circulatory Support in U.S. Children Awaiting Heart Transplantation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has long served as the
      standard of care for short-term mechanical circulatory support in pediatrics. It
      is unknown whether newer-generation temporary circulatory support (TCS) devices
      afford children a meaningful survival advantage over ECMO. OBJECTIVES: This study
      sought to determine whether bridge-to-heart transplant survival with a TCS device
      is superior to ECMO after adjusting for patient differences. METHODS: All
      children <=21 years of age listed for heart transplant from 2011 to 2015 who
      received a TCS device or ECMO as a bridge to transplant were identified using
      Organ Procurement and Transplantation Network data. Children supported with a TCS
      device were compared with a propensity score (PS)-matched cohort of children
      supported with ECMO as a bridge to transplant. The primary endpoint was Kaplan
      Meier survival to transplant. RESULTS: The number of TCS devices implanted in
      children increased from <=3 per year before 2011 to 50 in 2015. Overall, 93
      patients implanted with TCS devices were included for analysis (59% left
      ventricular assist devices, 23% right ventricular assist devices, 18%
      biventricular assist devices). The most commonly used device was the CentriMag
      PediMag system (65%), followed by TandemHeart (18%), Rotaflow (6%), and Impella
      (5%). Among 164 PS-matched patients, support duration was longer for the TCS
      cohort (median 19 days vs. 6 days; p < 0.001), and was longest for the CentriMag
      PediMag (24 days vs. 6 days; p < 0.001) with 27% supported for >60 days. Compared
      with the ECMO cohort, the PS-matched TCS cohort had longer survival to transplant
      (hazard ratio: 0.49; 95% confidence interval: 0.30 to 0.79) and longer overall
      survival (hazard ratio: 0.61; 95% confidence interval: 0.39 to 0.96), with 90-day
      mortality before transplant that was modestly reduced (from 45% with ECMO to 39%
      with TCS). CONCLUSIONS: The use of TCS devices in children as a bridge to
      transplant has risen rapidly in recent years, led by the growth of magnetically
      levitated centrifugal flow pumps. Compared with conventional ECMO, TCS durations
      are longer, and more importantly, patient survival is superior.

PMID- 29073954
TI  - Expanding the Use of Temporary Ventricular Assist Devices in Pediatric Patients:
      Rise of the Machines.

PMID- 29073956
TI  - Should Identifying a Titin Truncating Variant Change the Management of Patients
      With Dilated Cardiomyopathy?

PMID- 29073955
TI  - Phenotype and Clinical Outcomes of Titin Cardiomyopathy.
AB  - BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin
      truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose
      of this study was to establish relationships among TTNtv genotype, cardiac
      phenotype, and outcomes in DCM. METHODS: In this prospective, observational
      cohort study, DCM patients underwent clinical evaluation, late gadolinium
      enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated
      follow-up blinded to genotype for the primary composite endpoint of
      cardiovascular death, and major arrhythmic and major heart failure events.
      RESULTS: Of 716 subjects recruited (mean age 53.5 +/- 14.3 years; 469 men
      [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%)
      had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1
      years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2
      reduction; padjusted = 0.03) compared with patients without TTNtv. There was no
      difference in biventricular ejection fraction between TTNtv+/- groups. Overall,
      78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years;
      interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv
      (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite
      primary outcome of cardiovascular death, heart failure, or arrhythmic events, for
      patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92
      [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large,
      prospective, genotype-phenotype study of ambulatory DCM patients, we show that
      prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that
      TTNtv DCM does not appear to be associated with worse medium-term prognosis.

PMID- 29073959
TI  - Cardiology Takes the Hill!

PMID- 29073957
TI  - Interleukin-1 Beta as a Target for Atherosclerosis Therapy: Biological Basis of
      CANTOS and Beyond.
AB  - Inflammatory pathways drive atherogenesis and link conventional risk factors to
      atherosclerosis and its complications. One inflammatory mediator has come to the
      fore as a therapeutic target in cardiovascular disease. The experimental and
      clinical evidence reviewed here support interleukin-1 beta (IL-1beta) as both a
      local vascular and systemic contributor in this regard. Intrinsic vascular wall
      cells and lesional leukocytes alike can produce this cytokine. Local stimuli in
      the plaque favor the generation of active IL-1beta through the action of a
      molecular assembly known as the inflammasome. Clinically applicable interventions
      that interfere with IL-1 action can improve cardiovascular outcomes, ushering in
      a new era of anti-inflammatory therapies for atherosclerosis. The translational
      path described here illustrates how advances in basic vascular biology may
      transform therapy. Biomarker-directed application of anti-inflammatory
      interventions promises to help us achieve a more precise and personalized
      allocation of therapy for our cardiovascular patients.

PMID- 29073961
TI  - Recovery of Left Atrial Contractile Function After Maze Surgery in Persistent
      Longstanding Atrial Fibrillation.

PMID- 29073960
TI  - Menstrual Chest Pain in Women With History of Spontaneous Coronary Artery
      Dissection.

PMID- 29073958
TI  - Status of Early-Career Academic Cardiology: A Global Perspective.
AB  - Early-career academic cardiologists, who many believe are an important component
      of the future of cardiovascular care, face myriad challenges. The Early Career
      Section Academic Working Group of the American College of Cardiology, with senior
      leadership support, assessed the progress of this cohort from 2013 to 2016 with a
      global perspective. Data consisted of accessing National Heart, Lung, and Blood
      Institute public information, data from the American Heart Association and
      international organizations, and a membership-wide survey. Although the National
      Heart, Lung, and Blood Institute increased funding of career development grants,
      only a small number of early-career American College of Cardiology members have
      benefited as funding of the entire cohort has decreased. Personal motivation,
      institutional support, and collaborators continued to be positive influential
      factors. Surprisingly, mentoring ceased to correlate positively with obtaining
      external grants. The totality of findings suggests that the status of early
      career academic cardiologists remains challenging; therefore, the authors
      recommend a set of attainable solutions.

PMID- 29073962
TI  - Deferred Stenting in STEMI: Still an Interest in Selected Patients?

PMID- 29073963
TI  - Hormone Status Correlates With Incidence of Heart Failure.

PMID- 29073964
TI  - Reply: Deferred Stenting in STEMI: Still an Interest in Selected Patients?

PMID- 29073965
TI  - Reply: Hormone Status Correlates With Incidence of Heart Failure.

PMID- 29073968
TI  - Correction.

PMID- 29073969
TI  - Correction.

PMID- 29073967
TI  - Inhibition of Glycogen Synthase Kinase 3beta Blocks Mesomesenchymal Transition
      and Attenuates Streptococcus pneumonia-Mediated Pleural Injury in Mice.
AB  - Pleural loculation affects about 30,000 patients annually in the United States
      and in severe cases can resolve with restrictive lung disease and pleural
      fibrosis. Pleural mesothelial cells contribute to pleural rind formation by
      undergoing mesothelial mesenchymal transition (MesoMT), whereby they acquire a
      profibrotic phenotype characterized by increased expression of alpha-smooth
      muscle actin and collagen 1. Components of the fibrinolytic pathway (urokinase
      plasminogen activator and plasmin) are elaborated in pleural injury and strongly
      induce MesoMT in vitro. These same stimuli enhance glycogen synthase kinase (GSK)
      3beta activity through increased phosphorylation of Tyr-216 in pleural
      mesothelial cells and GSK-3beta mobilization from the cytoplasm to the nucleus.
      GSK-3beta down-regulation blocked induction of MesoMT. Likewise, GSK-3beta
      inhibitor 9ING41 blocked induction of MesoMT and reversed established MesoMT.
      Similar results were demonstrated in a mouse model of Streptococcus pneumoniae
      induced empyema. Intraperitoneal administration of 9ING41, after the induction of
      pleural injury, attenuated injury progression and improved lung function (lung
      volume and compliance; P < 0.05 compared with untreated and vehicle controls).
      MesoMT marker alpha-smooth muscle actin was reduced in 9ING41-treated mice.
      Pleural thickening was also notably reduced in 9ING41-treated mice (P < 0.05).
      Collectively, these studies identify GSK-3beta as a newly identified target for
      amelioration of empyema-related pleural fibrosis and provide a strong rationale
      for further investigation of GSK-3beta signaling in the control of MesoMT and
      pleural injury.

PMID- 29073970
TI  - Correction.

PMID- 29073971
TI  - Editorial - SI Lateral habenula.

PMID- 29073972
TI  - Thromboses and Cholangiocarcinoma.

PMID- 29073973
TI  - The Reply.

PMID- 29073974
TI  - Gastric Antral Vascular Ectasia and Metabolic Syndrome: Is There a Case for an
      Association?

PMID- 29073975
TI  - The Reply.

PMID- 29073976
TI  - Dual Antiplatelet Therapy Duration in Conservatively Managed Patients with Acute
      Coronary Syndrome: Any News?

PMID- 29073977
TI  - Corrigendum to "Consumers' behavior in quantitative microbial risk assessment for
      pathogens in raw milk: Incorporation of the likelihood of consumption as a
      function of storage time and temperature" (J. Dairy Sci. 99:1029-1038).

PMID- 29073978
TI  - Foreword.

PMID- 29073980
TI  - The undiagnosed pandemic: Burnout and depression within the surgical community.

PMID- 29073981
TI  - Applying Multi-Criteria Decision Analysis (MCDA) Simple Scoring as an Evidence
      based HTA Methodology for Evaluating Off-Patent Pharmaceuticals (OPPs) in
      Emerging Markets.
AB  - Off-patent pharmaceuticals (OPPs) represent more than 60% of the pharmaceutical
      market in many emerging countries, where they are frequently evaluated primarily
      on cost rather than with health technology assessment. OPPs are assumed to be
      identical to the originators. Branded and unbranded generic versions can,
      however, vary from the originator in active pharmaceutical ingredients, dosage,
      consistency formulation, excipients, manufacturing processes, and distribution,
      for example. These variables can alter the efficacy and safety of the product,
      negatively impacting both the anticipated cost savings and the population's
      health. In addition, many health care systems lack the resources or expertise to
      evaluate such products, and current assessment methods can be complex and
      difficult to adapt to a health system's needs. Multicriteria decision analysis
      (MCDA) simple scoring is an evidence-based health technology assessment
      methodology for evaluating OPPs, especially in emerging countries in which
      resources are limited but decision makers still must balance affordability with
      factors such as drug safety, level interchangeability, manufacturing site and
      active pharmaceutical ingredient quality, supply track record, and real-life
      outcomes. MCDA simple scoring can be applied to pharmaceutical pricing,
      reimbursement, formulary listing, and drug procurement. In November 2015, a
      workshop was held at the International Society for Pharmacoeconomics and Outcomes
      Research Annual Meeting in Milan to refine and prioritize criteria that can be
      used in MCDA simple scoring for OPPs, resulting in an example MCDA process and 22
      prioritized criteria that health care systems in emerging countries can easily
      adapt to their own decision-making processes.

PMID- 29073982
TI  - Drug Policy in Hungary.
AB  - We present a brief overview of the health care system in Hungary, focusing
      particularly on the pricing and reimbursement procedures of medicines. The
      National Institute of Health Insurance Fund Management is responsible for the
      administration of the health insurance system and public reimbursement of health
      technologies. There are two major types of reimbursement techniques in the
      outpatient care: the normative reimbursement is applied to all physicians and may
      be used for all indications listed in the Summary of Product Characteristics, and
      the indication-linked reimbursement is applied only to specialists who are
      authorized to prescribe the drug. Pharmaceuticals used in the inpatient care are
      fully reimbursed and are financed through diagnosis-related groups. Several cost
      containment measures such as external price referencing and internal price
      referencing with blind bidding are applied. Proposing managed entry agreements is
      a mandatory condition for reimbursing innovative pharmaceuticals. Compared with
      other countries in the region, the implementation of health technology assessment
      has a relatively long history in Hungary. The health technology assessment body
      critically evaluates reimbursement submissions of pharmaceuticals, simple medical
      devices, and complex medical devices such as hospital technologies.

PMID- 29073983
TI  - Drug Policy in Poland.
AB  - We presented a general overview of the health care system as well as the pricing
      and reimbursement environment in Poland. Poland aims to ensure proper access to
      safe and effective medicines while reducing patients' share in treatment costs.
      Nevertheless, the co-payment for pharmacotherapy is still high (more than 60%).
      The key policymaker and regulator in the system is the Ministry of Health, which
      is supported by the Polish Agency for Health Technology Assessment and Tariff
      System (Agencja Oceny Technologii Medycznych i Taryfikacji), responsible for
      evaluating applicant drugs, and the Economic Commission, responsible for
      negotiating the official sales prices and conditions for reimbursement with
      pharmaceutical companies (e.g., level of reimbursement and risk-sharing scheme
      agreements). The Agency for Health Technology Assessment and Tariff System
      dossier is obligatory for reimbursement application and includes the analysis of
      clinical effectiveness, economic analysis (with the threshold of quality-adjusted
      life-year established as no more than 3 times the gross domestic product per
      capita), and the analysis of budget impact. In Poland, only a positive list of
      reimbursed drugs is published and it is updated every 2 months. The following
      levels of reimbursement are in use: 100%, 70%, 50%, and lump sum (about ?0.8).
      The first reimbursement decision is given for a period of 2 years only, the
      second for 3 years, and the third for 5 years. There is no separate budget or
      special legal regulations for orphan drugs. Generic substitution of drugs is
      desired but not mandatory. Physicians are not assigned with pharmaceutical
      budgets. The access to real-world data is limited; the only registers available
      are for drugs used in drug programs.

PMID- 29073984
TI  - Drug Policy in Croatia.
AB  - We presented a general overview of the health care system as well as the pricing
      and reimbursement environment in Croatia. In Croatia, most of the public funding
      for health care is collected from employers, through mandatory health care
      contributions for all the employed citizens. This contribution is a dedicated tax
      reserved for the health care system derived from employees' salaries. The rest of
      the public funds is mainly from taxes used by the Ministry of Finance to
      complement the overall health budget each year. The population is covered by a
      basic health insurance plan provided by statute and optional insurance,
      administered by the Croatian Health Insurance Fund. Reimbursement decisions are
      based on the Ordinance of Ministry of Health issued in 2013, which is an
      ordinance establishing the criteria for inclusion of medicinal products in the
      Croatian Health Insurance Fund basic and supplementary drug lists. A health
      technology assessment agency was established in 2007 as a legal, public,
      independent, nonprofit institution under the Act on Quality of Health Care.
      Budget impact analysis is obligatory, and cost-effectiveness analysis is
      beneficial. Two reimbursement lists exist: the basic (100% drug coverage) and the
      supplementary (co-payment from 10% to 90%) lists. The basic list covers both
      hospital and retail drugs. There is also a special drug list for expensive drugs
      (mainly hospital drugs). International reference pricing is also in place. List
      updates are done on an yearly basis. Real-world evidence can be required for
      health technology assessment as evidence for the budget impact models and cost
      effective analysis; it is, however, not mandatory.

PMID- 29073985
TI  - Cost Evaluation of Inhaler Therapies Used in Respiratory Diseases: 1998--2015
      Period in Turkey.
AB  - BACKGROUND: With the rise in life expectancy, the burden of chronic diseases,
      including obstructive pulmonary diseases, has increased throughout the world.
      OBJECTIVES: To evaluate the sales trends of inhaler pharmaceuticals. METHODS: The
      changes in box sales and sales amounts (in Turkish lira) of inhaler
      pharmaceuticals during the period 1998 to 2015 were examined and sales were
      projected for the next 3 years. Pharmaceuticals were classified according to form
      and pharmacological groups. RESULTS: The sales of inhaler pharmaceuticals have
      increased rapidly since 2008. The fastest increase in consumption has occurred in
      short-acting beta2 agonist preparations and nebulizer pharmaceuticals. Inhaled
      corticosteroid and long-acting beta2 agonist combination sales have been the
      highest since 2002, when these products entered the Turkish market. CONCLUSIONS:
      The inhaler pharmaceutical market has grown over the years, and this growth will
      continue in the future. The increased use of short-acting preparations, which
      should be used as symptom relievers, indicates that treatment management
      continues to be inadequate.

PMID- 29073986
TI  - Functional Social Support for Hypertensive Patients in Primary Care Setting in
      Poland: What Is Expected and What Is Received?
AB  - OBJECTIVES: To measure expected and received functional social support (FSS) from
      doctors, nurses, and family members in the population of patients with primary
      arterial hypertension and to explore the gap between the expected and received
      support. METHODS: This cross-sectional study involved 232 adults in a primary
      arterial hypertension group and 115 healthy individuals in a control group. The
      sample was drawn from six family doctor surgeries in Szczecin, Poland. Three
      categories of expected and received FSS were examined, that is, emotional,
      informational, and instrumental, using the self-administered questionnaire. The
      Mann-Whitney U test was used to compare the means of received and expected
      support from different sources. Indexes of adequacy of FSS were established.
      RESULTS: A deep deficit of emotional support and a smaller deficit of
      informational and instrumental support from family members were observed in both
      groups. Hypertensive patients reported receiving a higher level of emotional and
      informational support than expected from doctors. Instrumental support from
      doctors and all three types of support from nurses met hypertensive patients'
      expectations. Healthy controls reported a distinct deficit in all kinds of
      support from doctors and nurses. Their expectations of informational and
      instrumental support from health professionals, and from family, were higher than
      those of the hypertensive patients. CONCLUSIONS: The study hypothesis predicting
      that Polish patients will perceive FSS received from family members as adequate
      and observe deficiencies in support from doctors and nurses was not confirmed.
      The low level of perceived emotional support from family requires attention from
      health educators to alleviate this deficiency.

PMID- 29073987
TI  - Drug Policy in Slovakia.
AB  - Slovak law sets clear rules and timelines in the process of approving the price
      and reimbursement of drugs. During the last decade, the Ministry of Health
      adopted several cost-containment measures in the price and reimbursement policy.
      The most effective measures were the implementation of the external referencing
      of drug prices in 2008 and the reimbursement law in 2011. The new act introduced
      several regulations such as making stricter rules for the referencing of prices,
      setting cost per quality-adjusted life-year threshold, and defining new rules for
      the setting of reimbursements. On one side, implementation of these measures
      helped to achieve visible cost savings, but, on the other side, cost-containment
      policies have had some unintended consequences. In recent years, Slovakia has
      been facing a decreased availability of drugs because of parallel exports. As a
      result of the government's effort, Slovakia is the only country in the European
      Union that implemented a legal ban on the re-export of medicines. During the
      decade before 2011, many innovative drugs were included in the reimbursement
      system. Because of stricter legal conditions introduced in 2011, there has been a
      gradual shift in reimbursing innovative drugs from the standard reimbursement
      system to reimbursement by way of exceptions of health insurance companies.
      Recently, there has been an ongoing discussion on possible changes to the
      reimbursement law.

PMID- 29073988
TI  - Drug Policy in Bulgaria.
AB  - Bulgaria has a mixed public-private health care financing system. Health care is
      financed mainly from compulsory health insurance contributions and out-of-pocket
      payments. Out-of-pocket payments constitute a large share of the total health
      care expenditure (44.14% in 2014). The share of drugs expenditure for outpatient
      treatment was 42.3% of the total health care expenditure in 2014, covered mainly
      by private payments (78.6% of the total pharmaceutical expenditure). The drug
      policy is run by the Ministry of Health (MoH), the National Council on Prices and
      Reimbursement of Medicinal Products, and the Health Technology Assessment
      Commission. The MoH defines diseases for which the National Health Insurance Fund
      (NHIF) pays for medicines. The National Council on Prices and Reimbursement of
      Medicinal Products maintains a positive drug list (PDL) and sets drug prices.
      Health technology assessment was introduced in 2015 for medicinal products
      belonging to a new international nonproprietary name group. The PDL defines
      prescription medicines that are paid for by the NHIF, the MoH, and the health
      care establishments; exact patient co-payments and reimbursement levels; as well
      as the ceiling prices for drugs not covered by the NHIF, including over-the
      counter medicines. The reimbursement level can be 100%, 75%, or up to 50%. The
      PDL is revised monthly in all cases except for price increase. Physicians are not
      assigned with pharmaceutical budgets, there is a brand prescribing practice, and
      the substitution of prescribed medicines by pharmacists is prohibited. Policies
      toward cost containment and effectiveness increase include introduction of a
      reference pricing system, obligation to the NHIF to conduct mandatory centralized
      bargaining of discounts for medicinal products included in the PDL, public
      tendering for medicines for hospital treatment, reduction of markup margins of
      wholesalers and retailers, patient co-payment, and the introduction of health
      technology assessment. Although most of the policies have been introduced since
      2011, there is still weak evidence for improvement regarding cost containment and
      effectiveness.

PMID- 29073989
TI  - Drug Policy in the Czech Republic.
AB  - BACKGROUND: The legal background of the current pharmaceutical pricing and
      reimbursement (P&R) setting in the Czech Republic is based on Act 48/1997. Since
      2008, the P&R process has been coordinated by the State Institute for Drug
      Control, which is the main stakeholder in the decision-making process; marketing
      authorization holders and insurance funds (IFs) also participate. OBJECTIVES: To
      present a general overview of the current Czech health care system and its P&R
      principles. METHODS: The study used publicly available sources concerning health
      care, mainly acts related to public health care and public health care insurance,
      public notices related to P&R setting, and statistical data. RESULTS: Regulation
      covers P&R. The official price represents the highest exfactory price, which
      cannot be exceeded. It is calculated as the mean of the three lowest prices in
      the European Union reference basket. Reimbursement is based on the lowest price
      per daily dose across the whole European Union. For reimbursement, products can
      be clustered into jumbo groups (mutually interchangeable), stated by law. In each
      group, reimbursement is set at the lowest price of any substance within the
      group. For highly innovative drugs a temporary reimbursement can be granted for a
      period of 3 years. During the administrative proceeding, efficacy, safety, cost
      effectiveness, and budget impact are assessed. The cost-effectiveness principles
      are aligned with the guidelines of the National Institute for Health and Clinical
      Care Excellence, preferring cost-utility analyses. The willingness-to-pay
      threshold has been implicitly set at 3 times the gross domestic product per
      capita. Products exceeding this threshold are subject to further risk-sharing
      negotiations. Budget impact is becoming increasingly important mainly for IFs.
      The IFs have recently introduced their own methodology, which allows only
      products with a budget impact in the range of CZK16 to CZK48 million (CZK = Czech
      koruna; ~?600,000 to ?1.8 million) to enter the system. Products exceeding this
      budget impact have to negotiate risk-sharing schemes, mainly further discounts
      and/or budget caps. CONCLUSIONS: The Czech pricing and reimbursement system is
      rather complex, taking into account clinical evidence, cost-effectiveness and
      budget impact. The strict regulations are a result of financial scarcity.

PMID- 29073990
TI  - Drug Policies in Central and Eastern European Countries.

PMID- 29073991
TI  - Concept of Combining Cost-Effectiveness Analysis and Budget Impact Analysis in
      Health Care Decision-Making.
AB  - OBJECTIVES: The objective of this study is to cover the ways of solving the
      problem of understanding the results of two key methods of pharmacoeconomic
      analysis - budget impact and cost-effectiveness. It is important to note that
      pharmacoeconomic assessment based on this evidence often has controversial
      character. The results of one type of analysis can characterize assessed health
      technology favorably, and the results of other critically. Pharmacoeconomic
      evidence is often a crucial part of decision-making in healthcare, that's why
      clear understanding of combination of this two types of analysis is highly in
      demand. METHODS: Authors propose methodological solution of the stated problem.
      This model is a useful tool in making unified pharmacoeconomic report based on
      cost-effectiveness analysis and budget impact analysis results. Use of this model
      preserves the meaning and significance of each type of pharmacoeconomic analysis.
      RESULTS: Three-dimensional pharmacoeconomic model proposes full account of both
      types of pharmacoeconomic analyses during conclusion preparation, the formation
      of a single consistent pharmacoeconomic conclusion. Though further validation of
      a tool is needed, presented model can be interesting for the professional
      community. CONCLUSIONS: The proposed model of combining budget impact and cost
      effectiveness analysis can be used by healthcare decision-makers for obtaining
      reliable and transparent pharmacoeconomic data.

PMID- 29073992
TI  - Ebola Virus Epidemic in West Africa: Global Health Economic Challenges, Lessons
      Learned, and Policy Recommendations.
AB  - The Ebola virus has spread across several Western Africa countries, adding a
      significant financial burden to their health systems and economies. In this
      article the experience with Ebola is reviewed, and economic challenges and policy
      recommendations are discussed to help curb the impact of other diseases in the
      future. The West African Ebola virus disease epidemic started in resource
      constrained settings and caused thousands of fatalities during the last epidemic.
      Nevertheless, given population mobility, international travel, and an
      increasingly globalized economy, it has the potential to re-occur and evolve into
      a global pandemic. Struggling health systems in West African countries hinder the
      ability to reduce the causes and effects of the Ebola epidemic. The lessons
      learned include the need for strengthening health systems, mainly primary care
      systems, expedited access to treatments and vaccines to treat the Ebola virus
      disease, guidance on safety, efficacy, and regulatory standards for such
      treatments, and ensuring that research and development efforts are directed
      toward existing needs. Other lessons include adopting policies that allow for
      better flow of relief, averting the adverse impact of strong quarantine policy
      that includes exaggerating the aversion behavior by alarming trade and business
      partners providing financial support to strengthen growth in the affected fragile
      economies by the Ebola outbreak. Curbing the impact of future Ebola epidemics, or
      comparable diseases, requires increased long-term investments in health system
      strengthening, better collaboration between different international
      organizations, more funding for research and development efforts aimed at
      developing vaccines and treatments, and tools to detect, treat, and prevent
      future epidemics.

PMID- 29073994
TI  - Advancing the Visibility, Impact, and Quality Metrics of Value in Health Regional
      Issues.

PMID- 29073993
TI  - Cost-Effectiveness Analysis of New HCV Treatments in Egyptian Cirrhotic and Non
      Cirrhotic Patients: A Societal Perspective.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of sofosbuvir (SOF) + ribavirin
      (RBV), SOF + daclatasvir (DCV), and SOF + ledipasvir (LDV) + RBV compared with
      SOF + pegylated interferon alfa (pegIFN) + RBV in the treatment of patients
      infected with hepatitis C virus in Egypt. METHODS: Two Markov models were
      developed on the basis of the Egyptian clinical data and practice and were
      derived from published sources. The clinical parameters were derived from two
      sources: the Egypt multicenter national treatment program and previously
      published randomized clinical trials. The utility of the health states was
      derived using the available published data. Direct medical costs were obtained
      from the National Liver Institute database. RESULTS: In noncirrhotic patients,
      incremental cost-effectiveness ratios of US $2330 per quality-adjusted life-year
      (QALY) gained for the SOF + LDV + RBV, -US $9043/QALY for the SOF + DCV, and -US
      $1332/QALY for the SOF + RBV regimens were yielded. In cirrhotic patients,
      incremental cost-effectiveness ratios of -US $4170/QALY gained for the SOF + LDV
      + RBV, -US $9515/QALY for the SOF + DCV, and -US $2289/QALY for the SOF + RBV
      regimens were yielded. The SOF + DCV regimen was the most cost-saving option for
      cirrhotic and noncirrhotic patients. Deterministic sensitivity analyses remain
      robust. CONCLUSIONS: The present study concludes that the SOF + DCV regimen among
      other currently available regimens is the most cost-saving option that yields the
      most favorable future health economic outcomes compared with the SOF + pegIFN +
      RBV regimen across a broad spectrum of patients, including those with cirrhosis.

PMID- 29073995
TI  - Drug Policy in Latvia.
AB  - We present a general overview of the health care system as well as the pricing
      and reimbursement environment in Latvia. Overall, the pharmaceutical sector in
      Latvia, including pricing and reimbursement, is strictly regulated. The main
      Latvian stakeholder in the pharmaceutical sector is the Ministry of Health. The
      State Agency of Medicines and the National Health Service (NHS) are also
      important institutions for regulation of pharmaceuticals, including pricing and
      reimbursement. The NHS is the most important institution for regulation of
      reimbursement of pharmaceuticals. It is responsible for health technology
      assessment and also for implementing decisions regarding the reimbursement of
      pharmaceuticals by including medicines in the positive reimbursement lists for
      outpatient care and defining positive lists of medicinal products for inpatient
      use. The reimbursement of expenditures for medicinal products and medicinal
      devices for outpatient care is a main part of drug funding in Latvia. Reference
      pricing is in place and prices are revised 4 times a year. The positive
      reimbursement list for outpatient care consists of three parts: list A, list B,
      and list C. All the medicines in the positive list are classified into one of
      three reimbursement categories (100%, 75%, or 50%) depending on the illnesses for
      which they have been approved. Pharmaceuticals used for inpatient care are
      included in the cost of inpatient services and are provided free of charge to
      patients. Inpatient drugs are purchased by health service providers.

PMID- 29073996
TI  - Battling Tuberculosis beyond antibiotics.
AB  - BACKGROUND: The incidence of tuberculosis (TB) in Cyprus has doubled over the
      last decade and an urgent overhaul is needed to curb its spread. OBJECTIVES: To
      analyze the incidence of TB on the basis of nationality, age, and sex and provide
      an insight on TB pattern in Cyprus. METHODS: We performed an odds ratio
      statistical analysis of the latest data and concluded that some nationalities are
      significantly associated with this increase. RESULTS: We identified that this can
      be partly attributed to a legislation gap, which provides that screening is
      mandatory only for third-country migrants, whereas there is no provision for high
      risk European migrants. CONCLUSIONS: On the basis of our findings, we suggest
      that health policies for TB in Cyprus be reformed and epidemiological findings be
      embedded in a revised integrated policy. This will make health policies more
      efficient and help contain scarce resources, both human and monetary.

PMID- 29073997
TI  - Synthesizing and Appraising the Quality of the Evidence on Factors Associated
      with Medication Adherence in Diabetes: A Systematic Review of Systematic Reviews.
AB  - BACKGROUND: Nonadherence to medications is a common phenomenon in patients with
      diabetes. Several studies and systematic reviews have investigated the barriers
      to medication adherence in diabetes. However, no study has evaluated the quality
      of the existing literature and synthesized the plethora of evidence with a goal
      to design holistic conceptual frameworks and interventions. OBJECTIVES: The aims
      of this review were to systematically evaluate existing systematic reviews
      focusing on factors associated with medication adherence in diabetes in an effort
      to synthesize the evidence, determine their methodological quality, and identify
      the gaps in the current literature. METHODS: Fourteen databases and gray
      literature sources were systematically searched through June 2016. Systematic
      reviews reporting factors associated with medication adherence (barriers and
      facilitators) in patients with diabetes were selected on the basis of
      predetermined criteria. Studies were appraised for quality using AMSTAR (A
      Measurement Tool to Assess Systematic Reviews). RESULTS: Seventeen systematic
      reviews including 542 primary studies, most of which were cross-sectional
      quantitative studies, were included. All the reviews were rated as moderate to
      low quality and exhibited common methodological pitfalls. Factors influencing
      medication adherence identified were categorized as patient-, medication-,
      disease-, health care provider-, health care system-, and social-related factors.
      CONCLUSIONS: Factors influencing medication adherence are multifactorial with
      remarkably consistent findings across the existing reviews; yet, most reviews
      were judged to be of low to moderate quality. Further comprehensive and well
      conducted original studies and systematic reviews on this topic shall be
      conducted taking into consideration the drawbacks of existing ones.

PMID- 29073999
TI  - Discrepancy Reporting ... Don't Bury the Hatchet in Someone Else's Back.

PMID- 29074000
TI  - How Can Radiologists and Radiology Journals Stay Current and Adapt to Open Access
      Publishing?

PMID- 29074001
TI  - Choosing Wisely Canada and Diagnostic Imaging: What Level of Evidence Supports
      the Recommendations?

PMID- 29074002
TI  - Novel thoughts on preterm birth research proceedings of the 13th annual preterm
      birth international collaborative (PREBIC) meeting.

PMID- 29074003
TI  - Therapeutic revolution in the management of diabetic retinopathy.

PMID- 29074004
TI  - Why we need to screen for diabetic eye disease.

PMID- 29074005
TI  - L'importance de proceder au depistage de l'oculopathie diabetique.

PMID- 29074006
TI  - Tele-ophthalmology for diabetic retinopathy in Canada-meeting the needs of a
      growing epidemic.

PMID- 29074007
TI  - Six-year prevalence and incidence of diabetic retinopathy and cost-effectiveness
      of tele-ophthalmology in Manitoba.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diabetic retinopathy
      (DR) tele-ophthalmology screening program in Manitoba to determine prevalence and
      incidence of DR, as well as to estimate the program's cost-effectiveness. DESIGN:
      Retrospective chart review. PARTICIPANTS: A total of 4676 patients with type 2
      diabetes examined 9334 times from 2007 to 2013. METHODS: Focused ophthalmic
      histories were recorded and examinations were performed by trained nurses,
      including visual acuities, intraocular pressure, and mydriatic 7 standard field
      stereoscopic fundus photography. Images were evaluated by retinal specialists
      according to the Early Treatment of Diabetic Retinopathy Study criteria. DR
      prevalence and incidence were then calculated during the study period. Cost
      effectiveness was estimated by comparing the cost of running the tele
      ophthalmology program compared with the cost of screening the same volume of
      patients in-office. RESULTS: The average prevalence of any DR in each year was
      25.1%. The cumulative incidence of DR across 6 years was 17.1% (95% CI, 15.4%
      18.7%). The average savings per tele-ophthalmology examination was $1007.
      CONCLUSIONS: DR is highly prevalent among the studied population. Tele
      ophthalmology provides a cost-effective means of monitoring patients as well as
      identifying new or treatable disease.

PMID- 29074009
TI  - La revolution du traitement de la retinopathie diabetique.

PMID- 29074008
TI  - Risk factors for progression of diabetic retinopathy in Alberta First Nations
      communities.
AB  - OBJECTIVE: The Screening for Limb, I-Eye, Cardiovascular, and Kidney
      Complications (SLICK) Program was implemented in 1999 to improve diabetic care
      for Alberta First Nations individuals living on reserve. The purpose of this
      review is to determine the rate and predictors of progression of diabetic
      retinopathy (DR) over a 10-year period. DESIGN: Cohort study. PARTICIPANTS: Nine
      hundred and eighty First Nations patients with diabetes that underwent at least 2
      teleophthalmology examinations during the study period. METHODS: Patients
      underwent serial laboratory testing, and stereoscopic, mydriatic, retinal
      photography. Modified Early Treatment Diabetic Retinopathy Study grading of
      retinal images was performed via teleophthalmology. Progression was defined as an
      increase of 2 or more steps on the Diabetes Control and Complications Trial
      classification. RESULTS: At baseline, most patients had no diabetic retinopathy
      (n = 777, 79.3%) whereas 203 people (20.7%) had either nonproliferative DR (n =
      179, 18.3%) or proliferative DR (n = 24, 2.5%). Two-step progression occurred in
      163 patients (16.6%), with only a minority of these individuals progressing to
      proliferative DR (n = 23). The median time to progression was 7.6 years.
      Multivariate Cox regression demonstrated that elevated hemoglobin A1C (hazard
      ratio [HR] = 1.42; p < 0.0001) and systolic blood pressure (HR = 1.24 per 10 mm
      Hg; p = 0.009) were independent predictors of progression of DR. CONCLUSIONS:
      This population-based study has shown that the rate and predictors of progression
      of DR among First Nations individuals parallels non-First Nations populations,
      with HbA1C and systolic blood pressure being the strongest predictors. These
      findings suggest that targeted, individualized care to reduce blood pressure and
      control blood sugars could reduce progression of diabetic retinopathy, and
      possibly blindness in First Nations individuals living on reserve.

PMID- 29074010
TI  - The role of occult hypertension in retinal vein occlusions and diabetic
      retinopathy.
AB  - OBJECTIVE: The aim of the study was to investigate whether individuals who
      develop retinal vein occlusion (RVO) or sudden-onset activity in otherwise
      quiescent diabetic retinopathy (DR) and those who have normal blood pressure (BP)
      or controlled hypertension according to their family physician show evidence of
      occult hypertension on 24-hour BP monitoring. METHODS: Patients with a new-onset
      RVO or DR that led to vitreous hemorrhage after a period of quiescence were
      identified. Informed consent was obtained, and patients were enrolled in the
      study if they met all of the inclusion criteria. Hypertension cut-offs were
      established in accordance with the Canadian Hypertension Education Program and
      the American Heart Association recommendations. All patients underwent a baseline
      BP measurement and 24-hour ambulatory BP monitoring. RESULTS: A total of 20
      patients were enrolled in the study. Eleven (55%) were female (mean age 67.5
      years). Seven patients (35%) had diabetes. Seventeen had retinal vein occlusions
      (85%), and 3 had sudden-onset activity in otherwise quiescent diabetic
      retinopathy (15%). Ten patients (50%) had no previous history of hypertension,
      and 10 (50%) had controlled hypertension on medications. Two patients (10%)
      failed to wear their BP cuff for the 24-hour duration and were excluded from the
      analysis. The average baseline systolic BP and diastolic BP were 133 and 78 mm
      Hg, respectively. Twelve patients (67%) tested positive for hypertension on their
      24-hour recording, and 5 (42%) of these patients had no history of hypertension.
      One of 12 patients (8%) had a positive nighttime average only but a normal
      daytime average. Nine of the 12 patients (75%) who had a positive recording had a
      subsequent change made to their medications. CONCLUSIONS: Uncontrolled
      hypertension is a known risk factor for the development of RVO and for vitreous
      hemorrhage in otherwise quiescent DR. Many of these patients may have occult
      hypertension that has not been detected by the currently usual standard. Twenty
      four-hour ambulatory BP monitoring is a useful and potentially lifesaving
      clinical test, which can detect uncontrolled hypertension, especially nocturnal
      hypertension, in this cohort of patients. The results of this test have important
      treatment implications that can help prevent or minimize further systemic
      complications.

PMID- 29074011
TI  - Analysis of reasons for noncompliance with laser treatment in patients of
      diabetic retinopathy.
AB  - OBJECTIVE: To identify the underlying reasons for noncompliance among Chinese
      patients undergoing laser photocoagulation treatment for diabetic retinopathy
      (DR). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 262 patients
      with DR with indications for panretinal photocoagulation and focal laser
      treatment were recruited. METHODS: Those who did not complete the prescribed
      laser treatment were categorized into 2 types of defaulters: Type 1 defaulters
      were those who did not initiate laser treatment as scheduled; type 2 defaulters
      were those who did not complete the entire laser sessions, including terminating
      midterm or defaulting prompt supplement of laser treatment. A standardized
      questionnaire was given to the 2 types of defaulters to collect information about
      the reasons for noncompliance. Data were analyzed and subjected to chi2 test or
      Fisher exact statistical tests. RESULTS: The noncompliance rate was 45.5%, which
      is significantly greater than some developed countries. Unawareness of the
      necessity for treatment and unawareness of the importance to complete treatment
      were 2 main reasons leading to noncompliance, representing 28.8% and 36.0%,
      respectively. Unawareness of the necessity for treatment and fear of laser
      treatment were more important for type 1 defaulters (29 vs 6 and 11 vs 0,
      respectively), whereas unawareness of completeness of laser treatment was
      overweighed in type 2 defaulters (27 vs 13 patients; all P<0.01). These results
      were likely related to the lack of knowledge about the potential consequences of
      DR, the underlying principle of laser treatment, and panretinal photocoagulation
      procedures. CONCLUSIONS: Developing appropriate education programs targeting
      specific reasons will help to improve the compliance in patients with DR.

PMID- 29074012
TI  - Relationship between vitamin D deficiency and diabetic retinopathy: a meta
      analysis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the evidence for an
      association between diabetic retinopathy (DR) and vitamin D deficiency. DESIGN:
      Meta-analysis. METHODS: We included 14 observational studies with 10 007
      participants who had undergone assessment for both DR and vitamin D deficiency.
      Pooled odds ratios (ORs) and 95% CIs were calculated using a random-effect,
      Mantel-Haenszel analysis. RESULTS: There was a statistically significant
      association between DR and vitamin D deficiency with an overall pooled OR of 1.27
      (95% CI, 1.17-1.37; P = 0.001; I2 = 80%; Pheterogeneity = 0.01). There was also a
      statistically significant lower serum vitamin D level in patient subgroups with
      DR versus control groups, with an overall mean difference of -1.32 ng/mL (95% CI,
      -2.50 to -0.15; P = 0.001; I2 = 89%; Pheterogeneity = 0.01). CONCLUSION: There is
      a statistically significant association between vitamin D deficiency and DR.

PMID- 29074013
TI  - Newer classes of antidiabetes drugs: ophthalmological considerations for GLP-1R
      agonists, DPP-4 inhibitors, and SGLT-2 inhibitors.

PMID- 29074014
TI  - Excerpt from the Canadian Ophthalmological Society evidence-based clinical
      practice guidelines for the management of diabetic retinopathy.

PMID- 29074015
TI  - Les " nouvelles " classes d'antidiabetiques: Considerations ophtalmologiques
      relatives aux agonistes du GLP-1R, aux inhibiteurs de la DPP-4 et aux inhibiteurs
      du SGLT2.

PMID- 29074016
TI  - Afterglow dosimetry performance of beta particle irradiated lithium zirconate.
AB  - In this work, we report for the very first time on the thermoluminescence (TL)
      and afterglow (AG) properties of Li2ZrO3. The ternary oxide Li2ZrO3 was
      synthesized by solid state reaction of a mixture of Li2CO3 and ZrO2 subjected to
      thermal annealing at 400 degrees C for 2h and 1000 degrees C during 24h in air.
      The characteristic glow curves of beta particle irradiated samples exhibit an
      intense TL emission located around 150 degrees C. From the shape of the TL curve,
      a 0.4 form factor was determined, suggesting that first order kinetics processes
      are involved. The afterglow decay curves were recorded after exposure to beta
      particle irradiation in the dose range from 0.5 up to 2kGy. The AG integrated in
      the time interval from 510 to 600s after radiation exposure shows a linear
      dependence as a function of the irradiation dose from 0.5 up to 256Gy. A method
      is proposed to compute the lower detection limit and the AG sensitivity and
      applied to the studied phosphors. Structural and morphological characterization
      were carried out by X-ray diffraction and Scanning Electron Microscopy,
      respectively. From the results presented, it is concluded that the AG response of
      the synthesized Li2ZrO3 presents features suitable to develop radiation detectors
      and dosimeters.

PMID- 29074017
TI  - 230U nuclear decay data evaluation.
AB  - The evaluation of the nuclear decay data of 230U, a radionuclide of interest in
      nuclear medicine (targeted alpha therapy), was performed within the Decay Data
      Evaluation Project (DDEP) and an IAEA Coordinated Research Project. The nuclear
      decay data presented are: the half-life, decay energy, alpha-particle emission
      energies and probabilities, internal conversion coefficients and gamma-ray
      energies and emission intensities. These new data, obtained using the DDEP
      methodology and software tools, will be included in the DDEP database NUCLEIDE.

PMID- 29074018
TI  - Herpes zoster infection of the breast in the diferential diagnosis of mastitis.

PMID- 29074019
TI  - Assessing and modeling the thermal impact of the human-clothing environment.

PMID- 29074020
TI  - Predication of skin temperature and thermal comfort under two-way transient
      environments.
AB  - In this study, three transient environmental conditions consisting of one high
      temperature phase within two low-temperature phases were developed, thus creating
      a temperature rise followed by a temperature fall. Twenty-four subjects
      (including 12 males and 12 females) were recruited and they underwent all three
      test scenarios. Skin temperature on seven body parts were measured during the
      whole period of the experiment. Besides, thermal sensation was investigated at
      specific moments by questionnaires. Thermal sensation models including PMV model,
      Fiala model and the Chinese model were applied to predict subjects' thermal
      sensation with comparisons carried out among them. Results show that most
      predicated thermal sensation by Chinese model lies within the range of 0.5 scale
      of the observed sensation vote, and it agrees best with the observed thermal
      sensation in transient thermal environment than PMV and Fiala model. Further
      studies should be carried out to improve performance of Chinese model for
      temperature alterations between "very hot" to "hot" environment, for prediction
      error in the temperature-fall situation of C5 (37-32 degrees C) was over 0.5
      scale.

PMID- 29074021
TI  - A human thermoregulation model for the Chinese elderly.
AB  - Older people are always more vulnerable to thermal-related discomfort and health
      issues because of their diminishing ability to adapt to varying environmental
      conditions. There exist a few thermoregulation models but most of them did not
      consider age and ethnic differences. In this study, a standard thermoregulation
      model for Chinese elders was developed on the basis of literature review and the
      already established model for the Chinese young people. Furthermore, the standard
      model was individualized with four parameters (height, weight, sex and age) for
      more accurate prediction. Besides, both models were validated with experimental
      data. Results show that the standard model prediction-measurement discrepancies
      of the skin temperatures lay in the range of S.D. of measurements. Compared to
      the standard model, there were some improvements in the individualized model,
      especially for old men. Further validation with published experimental data
      indicated good predictions were also in good agreement with measurements. The
      work in the paper may play an important role in providing a more healthy and
      comfortable indoor environment for the elderly.

PMID- 29074022
TI  - A field study of the effectiveness and practicality of a novel hybrid personal
      cooling vest worn during rest in Hong Kong construction industry.
AB  - A novel hybrid cooling vest (HCV) incorporated with phase change materials (PCMs)
      and ventilation fans has been developed for construction workers in Hong Kong to
      attenuate heat stress and prevent heat-related illnesses, and its effectiveness
      and practicality have been validated in this study. A total of 140 wear trials
      involving of 140 workers were conducted in Hong Kong construction sites during
      the summer time. Each wear trial involves a two-day wear test, of which one day
      workers wore the HCV (denoted as VEST) during resting, and another day they wore
      traditional workwear (denoted as CON). Subjects were asked to rate their
      perceived exertion (RPE), thermal sensations (TS) and 7 other subjective
      attributes. There were significant differences in the effectiveness on reducing
      workers' heat strain between VEST and CON in terms of alleviations of heart rate
      (DeltaHR), DeltaTS, DeltaRPE as well as DeltaPeSI (p < 0.001). The practicality
      of HCV is evidenced by a significant improvement by 0.93-1.34 on the rating
      scores of perceived cooling effect, sensations of comfort and skin dryness during
      rest and fatigue recovery in VEST at the level of 0.05, and high ratings of 4.85
      5 (rating scale from 1 to 7, and the higher the better) by subjects on the
      preference, fitness as well as effectiveness to combat heat stress. In addition,
      a remarkable proportion of 91 per cent of subjects prefer to use this newly
      designed HCV as a cooling measure during rest. The power to alleviate perceptual
      heat stain (PeSA) in VEST is about twice of that by rest, which means HCV can
      notably improve the workers' perceptual heat strain in a limited resting
      duration. However, the strain alleviation power of HCV nearly remains unchanged
      with the prolonged rest duration. Thus, the optimal work-rest schedule needs to
      be investigated in a further study.

PMID- 29074023
TI  - The relationship between thermal environments and clothing insulation for elderly
      individuals in Shanghai, China.
AB  - The relationship between thermal environmental parameters and clothing insulation
      is an important element in improving thermal comfort for the elderly. A field
      study was conducted on the indoor, transition space, and outdoor thermal
      environments of 17 elderly facilities in Shanghai, China. A random questionnaire
      survey was used to gather data from 672 valid samples. A statistical analysis of
      the data was conducted, and multiple linear regression models were established to
      quantify the relationships between clothing insulation, respondent age, indoor
      air temperature, and indoor relative humidity. Results indicated that the average
      thermal insulation of winter and summer clothing is 1.38 clo and 0.44 clo,
      respectively, for elderly men and 1.39 clo and 0.45 clo, respectively, for
      elderly women. It was also found that the thermal insulation of winter clothing
      is linearly correlated with age, and that there were seasonal differences in the
      relationship between clothing insulation and the environment. During winter, the
      clothing insulation is negatively correlated only with indoor temperature
      parameters (air temperature and operative temperature) for elderly males, while
      it is negatively correlated with indoor temperature parameters as well as
      transition space and outdoor air temperature for elderly females. In summer,
      clothing insulation for both elderly males and females is negatively correlated
      with outdoor temperature, as well as indoor temperature parameters (air
      temperature and operative temperature). The thermal insulation of summer clothing
      is also negatively correlated with transitional space temperature for males.

PMID- 29074024
TI  - An investigation of thermophysiological responses of human while using four
      personal cooling strategies during heatwaves.
AB  - This study aimed to examine how human body thermophysiologically responds to four
      commonly used cooling strategies (i.e., electric fan cooling [AirFC], evaporative
      cooling clothing [EvapCC], hybrid cooling, i.e., evaporative cooling clothing
      combined with electric fan cooling [EvapCC&AirFC] and liquid cooling clothing
      [LiqCC]) during heatwaves. An adaptive 'Newton' manikin was used to predict human
      physiological responses while using these four cooling systems. Four heatwave
      conditions were selected, i.e., 36 degrees C, 33% RH (hot-dry, denoted as HD1),
      36 degrees C, 67% RH (hot-humid, denoted as HH1), 40 degrees C, 27% RH (extremely
      hot-dry, denoted as HD2) and 40 degrees C, 54% RH (extremely hot-humid, denoted
      as HH2). A metabolic rate of 2.5 METs was used to mimic moderate work while
      sitting at either home or outdoors. AirFC was only found to bring cooling
      benefits in HD1 and HH1. EvapCC was effective in both HD1 and HD2. LiqCC showed
      similar cooling benefits compared to EvapCC in HD1 and HD2, and also displayed
      cooling benefits in HH1. EvapCC&AirFC was discovered to be most effective cooling
      strategy in the four studied conditions. Concerning their practical applications,
      EvapCC&AirFC was recommended to inactive populations while staying indoors during
      different heatwave conditions, and EvapCC and LiqCC were more suitable for active
      populations while working/exercising in hot-dry conditions and hot-humid
      conditions, respectively.

PMID- 29074025
TI  - Human responses in heat - comparison of the Predicted Heat Strain and the Fiala
      multi-node model for a case of intermittent work.
AB  - Two mathematical models of human thermal regulation include the rational
      Predicted Heat Strain (PHS) and the thermophysiological model by Fiala. The
      approaches of the models are different, however, they both aim at providing
      predictions of the thermophysiological responses to thermal environments of an
      average person. The aim of this study was to compare and analyze predictions of
      the two models against experimental data. The analysis also includes a gender
      comparison. The experimental data comprised of ten participants (5 males, 5
      females, average anthropometric values were used as input) conducting an
      intermittent protocol of rotating tasks (cycling, stacking, stepping and arm
      crank) of moderate metabolic activities (134-291W/m2) with breaks in-between in a
      controlled environmental condition (34 degrees C, 60% RH). The validation
      consisted of the predictions' comparison against experimental data from 2.5h of
      data of rectal temperature and mean skin temperature based on contact thermometry
      from four body locations. The PHS model over-predicted rectal temperatures during
      the first activity for males and the cooling effectiveness of sweat in the
      recovery periods, for both males and females. As a result, the PHS simulation
      underestimated the thermal strain in this context. The Fiala model accurately
      predicted the rectal temperature throughout the exposure. The fluctuation of the
      experimental mean skin temperature was not reflected in any of the models.
      However, the PHS simulation model showed better agreement than the Fiala model.
      As both models predicted responses more accurately for males than females, we
      suggest that in future development of the models it is important to take this
      result into account. The paper further discusses possible sources of the observed
      discrepancies and concludes with some suggestions for modifications.

PMID- 29074026
TI  - Numerical investigation of airflow, heat transfer and particle deposition for
      oral breathing in a realistic human upper airway model.
AB  - Inhalation injury from exposure to fire smoke is one of the causes of burn
      related death. In this study, a realistic three-dimensional human upper airway
      model was built from magnetic resonance imaging (MRI) scanned images, including
      the nasal, oral, pharynx, larynx, trachea and part of the first generation of the
      tracheobronchial tree, as well as a tissue region from the pharynx to the upper
      bronchi. The Transition Shear Stress Transport (SST-transition) turbulence model,
      Pennes bioheat transfer equation, convective boundary conditions and a Lagrangian
      frame were applied and verified with experimental measurements to simulate the
      airflow fields, temperature distributions and particle deposition in the human
      airway model. The effects of flow rate, inhalation temperature and particle
      diameter were studied. It showed that the oral cavity is more likely to be
      affected by the inlet air conditions. The mucosa in the oral, pharynx and larynx
      are more likely to cause the thermal injury. The inspiration flow rate
      significantly influences the airflow fields, temperature distributions and
      particle deposition fraction interior of the human upper airway model, especially
      in the pharynx-larynx region. The rising flow rate, inhalation air temperature
      and particle diameter all contribute to boosting the total deposition fraction in
      the model. The heated particles with a higher temperature are more likely to be
      deposited in the oral cavity and the influence of the inlet temperature has a
      minor influence in the case of a bigger particle diameter.

PMID- 29074027
TI  - An innovative HVAC control system: Implementation and testing in a vehicular
      cabin.
AB  - Personal vehicles undergo rapid development in every imaginable way. However, a
      concept of managing a cabin thermal environment remains unchanged for decades.
      The only major improvement has been an automatic HVAC controller with one user's
      input - temperature. In this case, the temperature is often deceiving because of
      thermally asymmetric and dynamic nature of the cabins. As a result, the effects
      of convection and radiation on passengers are not captured in detail what also
      reduces the potential to meet thermal comfort expectations. Advanced
      methodologies are available to assess the cabin environment in a fine resolution
      (e.g. ISO 14505:2006), but these are used mostly in laboratory conditions. The
      novel idea of this work is to integrate equivalent temperature sensors into a
      vehicular cabin in proximity of an occupant. Spatial distribution of the sensors
      is expected to provide detailed information about the local environment that can
      be used for personalised, comfort driven HVAC control. The focus of the work is
      to compare results given by the implemented system and a Newton type thermal
      manikin. Three different ambient settings were examined in a climate chamber.
      Finally, the results were compared and a good match of equivalent temperatures
      was found.

PMID- 29074028
TI  - Effects of fabric thickness and material on apparent 'wet' conductive thermal
      resistance of knitted fabric 'skin' on sweating manikins.
AB  - Currently, no published standard and research work have addressed the basic
      requirements on knitted fabric 'skin' on sweating manikins. In this study, we
      performed 252 experiments to investigate the influence of fabric thickness and
      material on the apparent 'wet' conductive (or effective) thermal resistance of
      the fabric 'skin' using a 'Newton' manikin. Four types of cotton fabric 'skin'
      (fabric thickness: 0.38, 0.54, 0.92 and 1.43mm) and three types of polyester
      fabric 'skin' (fabric thickness: 0.41, 0.54 and 1.0mm) were selected and their
      'wet' conductive thermal resistance was determined. Empirical equations were also
      developed for each fabric 'skin' to predict wet fabric 'skin' surface
      temperatures. It was found that both fabric thickness and material significantly
      affected the apparent 'wet' conductive thermal resistance. Clothing total
      evaporative resistance determined using thin fabric 'skin' (e.g., CO1, CO2) was
      normally lower than that determined using thick fabric 'skin' (e.g., CO4).
      Besides, synthetic fabric 'skin' tended to have a larger apparent 'wet'
      conductive thermal resistance than the cotton fabric 'skin' due to a smaller
      amount of moisture contained. Hence, there is a great need to standardize the
      fabric 'skin' to eliminate the influence of fabric 'skin' on the measurement of
      clothing evaporative resistance by means of a sweating manikin.

PMID- 29074029
TI  - Ultrastructural Integrity of Human Capsulotomies Created by a Thermal Device.
AB  - PURPOSE: To investigate the ultrastructural features of anterior capsulotomy
      performed with a thermal device, the precision pulse capsulotomy (PPC). DESIGN:
      Prospective, multicenter case series. PARTICIPANTS: Consecutive patients
      undergoing capsulotomy with the PPC device. METHODS: Prospective study of
      patients undergoing capsulotomy with the PPC by 2 surgeons, followed up by
      routine phacoemulsification cataract surgery, was undertaken. All capsulotomy
      specimens were collected for scanning electron microscopy (SEM). Observations
      were made regarding uniformity of the capsular edge and the presence of
      irregularities that may compromise integrity. Comparisons were made with manual
      continuous curvilinear capsulorrhexis. MAIN OUTCOME MEASURES: Ultrastructural
      features of PPC and presence of irregularities. RESULTS: Frayed appearance of the
      anterior capsule edge was noted in postoperative visits under slit-lamp
      examination. Scanning electron microscopy sampling showed a generally uniform
      rolled capsular edge, but interspersed with areas of irregularity with frayed
      appearance at the capsule margin. CONCLUSIONS: The PPC device is capable of
      creating reproducible, central, and precise circular capsulotomy. The
      ultrastructural features in ex vivo human capsulotomy specimens generally show
      eversion of the capsulotomy edge, but in some cases, this was accompanied by
      areas of irregular capsule margin with frayed edges, likely caused by dissipated
      thermal energy. The postoperative appearance and SEM features warrant further
      assessment of the PPC integrity and clinical correlation.

PMID- 29074030
TI  - Reliable Rapid Assay for Gonorrhea and Chlamydia in the Emergency Department.
AB  - BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are common
      sexually transmitted infections seen in the emergency department (ED). Due to an
      inability to reliably make accurate diagnosis by physical examination, concern
      for unreliable follow-up, and current delays in diagnostic nucleic acid
      amplification testing (NAAT), presumptive treatment active against CT and NG, as
      described by Centers for Disease Control clinical practice guidelines, is often
      performed. OBJECTIVES: The purpose of this study was to determine whether a
      rapid, urine NAAT performed in the ED is noninferior in its diagnostic
      sensitivity compared with a traditional, swab NAAT assay. METHODS: We performed a
      prospective, noninferiority study comparing two U.S. Food and Drug Administration
      approved NAAT assays for CT and NG: a 90-min rapid assay, the Xpert CT/NG Assay
      (Cepheid, Sunnyvale, CA) using a urine sample vs. a traditional assay, the Aptima
      Combo 2 Assay (Gen-Probe Incorporated, San Diego, CA) using a swab sample. This
      study was registered on Clinicaltrials.gov (NCT02386514). RESULTS: A total of
      1162 patient samples were included in the primary analysis. We observed excellent
      kappa agreement between assays: NG for men, 1.00 (95% confidence interval [CI]
      1.00-1.00); NG for women, 0.87 (95% CI 0.79-0.94); CT for men, 0.81 (95% CI 0.59
      1.00); and CT for women: 0.85 (95% CI 0.80-0.90), as well as excellent negative
      and positive predictive values for the rapid assay. CONCLUSION: Although the
      rapid Xpert CT/NG assay's diagnostic sensitivity did not meet our prespecified
      threshold for noninferiority, the diagnostic characteristics are robust enough to
      fit into a management pathway that may reduce unnecessary antibiotic use. There
      may be an opportunity to utilize the rapid Xpert CT/NG assay to improve accuracy
      of treatment in the ED.

PMID- 29074031
TI  - Do Emergency Physicians Improve the Appropriateness of Emergency Transfer in
      Rural Areas?
AB  - BACKGROUND: Until recently, there have been few studies on the transfer of
      patients from emergency departments (EDs) overall, as such studies were limited
      primarily to trauma patients. OBJECTIVES: The purpose of this study was to
      investigate the association between the specialty of the primary referring
      physician and the appropriateness of the emergency transfer (AET). METHODS: This
      was a retrospective, observational study performed at two level-3 EDs in a rural
      area. A transfer to a higher-level ED for the purpose of patient stabilization
      was defined as an emergency transfer, and transfers were classified as
      "appropriate" when the emergency status of the patient could not be resolved by
      the referring ED. The primary outcome was AET, which was reviewed by an expert
      panel for reliability. Statistically significant variables were selected as
      covariates based on the results of a univariate analysis, and a multivariate
      logistic regression analysis was performed to estimate the odds ratios (ORs) with
      95% confidence intervals (CIs) on the AET. RESULTS: A total of 1325 patients
      underwent transfer to another hospital from the two EDs. Of these, 1003 were
      classified into the emergency transfer group. In both EDs, the incidence of
      appropriate emergency transfers was significantly higher when the primary
      referring physician was an emergency physician (OR 4.005, 95% CI 2.619-6.125 and
      OR 4.006, 95% CI 1.696-9.459 for each hospital, respectively). CONCLUSION: There
      was a positive association between the specialty of the primary referring
      physician and the AET among EDs located in rural areas making patient transfers.

PMID- 29074032
TI  - Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers.
AB  - The brain changes as we age and these changes are associated with functional
      deterioration and neurodegenerative disease. It is vital that we better
      understand individual differences in the brain ageing process; hence, techniques
      for making individualised predictions of brain ageing have been developed. We
      present evidence supporting the use of neuroimaging-based 'brain age' as a
      biomarker of an individual's brain health. Increasingly, research is showing how
      brain disease or poor physical health negatively impacts brain age. Importantly,
      recent evidence shows that having an 'older'-appearing brain relates to advanced
      physiological and cognitive ageing and the risk of mortality. We discuss
      controversies surrounding brain age and highlight emerging trends such as the use
      of multimodality neuroimaging and the employment of 'deep learning' methods.

PMID- 29074033
TI  - Pre-ovulatory follicle affects corpus luteum diameter, blood flow, and
      progesterone production in mares.
AB  - Color Doppler ultrasonography was used to study the temporal relationships
      between pre-ovulatory follicle (POF) and corpus luteum (CL) diameter and blood
      flow, with systemic progesterone (P4) concentration during two transitional
      ovulatory seasons in mares. Variables of POF and CL/P4 were evaluated for 6days
      before and 17days after ovulation, respectively. Evaluations were performed
      during two consecutive estrous cycles in spring and fall seasons, and during the
      last estrous cycle of the season. There were significant correlations among POF
      and CL variables, and P4 concentration that ranged from 0.24 to 0.95, and among
      the ratios of different variables that ranged from 0.39 to 0.92. There were
      linear regressions (P<0.01-0.001) for all comparisons among different variables.
      The POF diameter before the first ovulation of the season was larger (P<0.05),
      and POF vascularity was less (P<0.05), than in the last estrous cycle during the
      season. The CL blood flow was less (P<0.01) during the last compared with first
      pre-ovulatory period of the season. The POF diameters were positively correlated
      (r=0.67) during the two pre-ovulatory periods of spring and fall. Results provide
      evidence that the POF affects CL diameter and blood flow, and subsequently P4
      production, and that POF diameter is repeatable within the same individual during
      different seasons.

PMID- 29074034
TI  - Colony stimulating factors (CSFs): Complex roles in atherosclerosis.
AB  - Colony stimulating factors (CSFs) play a central role in the development and
      functional maturation of immune cells besides having pleiotropic effects on cells
      of the vascular wall. The production of CSFs is induced by multiple atherogenic
      and inflammatory stimuli and their expression levels are often correlated
      positively with advanced atherosclerotic plaques and adverse cardiovascular
      events in humans suggesting that CSFs play a critical role in the pathophysiology
      of atherosclerosis progression. Interestingly, recombinant CSFs as well as anti
      CSFs are being increasingly used for diverse clinical indications. However, the
      effect of these novel therapeutics on atherosclerotic plaque progression is not
      well understood. Herein, we summarize the currently available literature on the
      complex role of CSFs in various stages of atherosclerosis and emphasize the
      necessity for conducting further mechanistic studies in animal models of
      atherosclerosis as well as the need for evaluating the cardiovascular safety of
      CSF-based therapies in humans.

PMID- 29074035
TI  - The IL-12 cytokine family in cardiovascular diseases.
AB  - Cytokines of the Interleukin (IL)-12 family, consisting of IL-12, IL-23, IL-27
      and IL-35, are important regulators in (chronic) inflammatory disorders such as
      rheumatoid arthritis and multiple sclerosis, but also in cardiovascular diseases.
      Cytokines of the IL-12 family consist of two subunits and are known for their
      regulatory functions in the immunologic response, more specifically in the
      regulation and differentiation of T-helper (Th) cells such as Th1 and Th17 cells.
      Binding of these cytokines to its specific heterodimeric receptor results in the
      activation of the JAK-STAT signaling. Despite similarities in structure, the
      members of the IL-12 family have diverse, both pro- and anti-inflammatory,
      effects and functions. Because of the pro-inflammatory effects of IL-12 cytokine
      family members on immune responses, the IL-12 cytokines have been implicated in
      the development and progression of cardiovascular diseases such as
      atherosclerosis, but also in acute cardiovascular syndromes such as myocardial
      infarction and stroke. For example, patients suffering from cardiovascular
      disease display increased blood levels of IL-12, IL-23 and IL-27, while decreased
      IL-35 levels have been linked to a lower cardiovascular risk. In this review, we
      aim to highlight the current understandings of the IL-12 cytokine family and its
      specific family members to cardiovascular diseases, including both clinical and
      experimental studies. We will also discuss the potential of these cytokines as a
      biomarker in acute cardiovascular syndromes.

PMID- 29074036
TI  - Developmental and behavioral aspects of mucopolysaccharidoses with brain
      manifestations - Neurological signs and symptoms.
AB  - The mucopolysaccharidoses (MPS) are a group of rare, inherited lysosomal storage
      disorders, caused by mutations in lysosomal enzymes involved in the degradation
      of glycosaminoglycans (GAGs). The resulting accumulation of GAGs in the body
      leads to widespread tissue and organ dysfunction. The spectrum, severity, and
      progression rate of clinical manifestations varies widely between and within the
      different MPS types. In addition to somatic signs and symptoms, which vary
      between the different MPS disorders, patients with MPS I, II, III, and VII
      present with significant neurological signs and symptoms, including impaired
      cognitive abilities, difficulties in language and speech, and/or behavioral and
      sleep problems. To effectively manage and develop therapies that target these
      neurological manifestations, it is of utmost importance to have a profound
      knowledge of their natural history and pathophysiology. This review describes the
      appearance and progression of neurological signs and symptoms in patients with
      MPS I, II, and III, based on presentations and discussions among an international
      group of experts during a meeting on the brain in MPS on April 28-30, 2016, and
      additional literature searches on this subject.

PMID- 29074037
TI  - High-intensity focused ultrasound therapy.
AB  - High-intensity focused ultrasound therapy has received increasing interest in the
      management of benign uterine tumors. Either magnetic resonance or ultrasound
      imaging has been used to target and monitor the ablation process. This article
      provides an overview of the background, clinical use, treatment outcomes, and
      safety of high-intensity focused ultrasound in the treatment of uterine fibroids
      and adenomyosis, including a summary of clinical trials comparing magnetic
      resonance- or ultrasound-guided high-intensity focused ultrasound with other
      minimally invasive or surgical interventions. The potential of this treatment
      modality as an alternative uterus-sparing option for women with fibroids and
      adenomyosis is discussed.

PMID- 29074038
TI  - Protection of the house against Chagas disease, dengue, leishmaniasis, and
      lymphatic filariasis: a systematic review.
AB  - In light of the recent Zika virus outbreak, vector control has received renewed
      interest. However, which interventions are efficacious and community effective
      and how to best deliver them remains unclear. Following PRISMA guidelines, we did
      a systematic review to assess evidence for applied vector control interventions
      providing protection against Chagas disease, dengue, leishmaniasis, and lymphatic
      filariasis at the household level. We searched for published literature and grey
      literature between Jan 1, 1980, and Nov 30, 2015, and updated our search on April
      2, 2017, using databases including the Cochrane, Embase, LILACS, PubMed, Web of
      Science, and WHOLIS. The Cochrane Collaboration's tool for assessing risk of bias
      was used. Inclusion criteria included studies reporting vector control
      interventions in and around a house or dwelling; and use of insecticides as
      sprays on netting or screens, and any method to control larval breeding in water
      containers in and around the home. 1416 articles were assessed and 32 articles
      included. The most effective interventions affecting vector indices for multiple
      diseases were found to be intradomiciliary residual spraying, insecticide-treated
      materials (especially insecticide-treated nets or curtains), and treatment of
      larval habitats with biological and chemical methods. Waste management and clean
      up campaigns reduce vector populations, although to a lesser extent than other
      interventions and not consistently. Modifications to the structure of homes (eg,
      wall plastering) had no impact on the control of vectors. Protection of the house
      and its surroundings might affect the transmission of several diseases. The most
      effective interventions should be prioritised when vector control programmes are
      designed; however, the quality of delivery (ie, coverage and reapplication) of
      interventions is a crucial factor to ensure their effectiveness. Additional
      randomised trials that assess the measures of human disease and eventually target
      several diseases with a combination of interventions that protect the household
      and its inhabitants against multiple vectors, are needed to inform global policy
      in this area.

PMID- 29074039
TI  - Percutaneous coronary intervention of bifurcation lesions and platelet
      reactivity.
AB  - BACKGROUND: Although bifurcation percutaneous coronary intervention (PCI) is
      associated with lower procedural success rates and higher risk of complications,
      there are little data regarding outcomes after successful bifurcation PCI with
      contemporary stents and techniques. Whether residual platelet reactivity (PR)
      affects outcomes differently after bifurcation versus non-bifurcation PCI is also
      unknown. We studied the association between bifurcation PCI, PR, and clinical
      outcomes among patients undergoing successful PCI with drug-eluting stents.
      METHODS: Patients in the prospective, multicenter ADAPT-DES study were stratified
      according to whether they underwent bifurcation PCI. Two-year outcomes were
      compared between groups using Cox proportional hazards models. Target vessel
      failure (TVF) was defined as the composite of all-cause death, myocardial
      infarction, and ischemia-driven target vessel revascularization. RESULTS: Among
      the 8582 patients included in ADAPT-DES, 1276 (15%) had bifurcation PCI.
      Bifurcation PCI was independently associated with increased risk of TVF (adjusted
      hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.08-1.46, p=0.003), driven
      by higher risk of myocardial infarction (5.9% vs. 4.6%, p=0.033) and ischemia
      driven target vessel revascularization (13.0% vs. 9.2%, p<0.0001). There was no
      statistical interaction between PR and bifurcation PCI regarding TVF risk
      (adjusted pinteraction=0.87). Stenting of both bifurcation branches was
      associated with the highest risk of TVF (adjusted HR 1.91, 95% CI 1.48-2.46
      versus non-bifurcation PCI; ptrend<0.001). CONCLUSIONS: Bifurcation PCI is
      associated with a higher risk of 2-year adverse ischemic events than non
      bifurcation PCI, a risk that is particularly high when both bifurcation branches
      are stented, and with HPR conferring similar risk for bifurcation and non
      bifurcation PCI.

PMID- 29074040
TI  - Heart failure and inflammation-related biomarkers as predictors of new-onset
      diabetes in the general population.
AB  - BACKGROUND: There is a strong reciprocal relationship between heart failure (HF)
      and diabetes mellitus (DM). Shared pathophysiological mechanisms might be a
      possible explanation. Therefore, we hypothesised that biomarkers linked to HF
      would also predict new-onset type 2 DM in the general population. METHODS AND
      RESULTS: We utilized the Prevention of Vascular and Renal End-stage Disease
      (PREVEND) cohort (mean age 48.9years, 51% female) to study the relationship
      between HF and DM in 7953 participants free of baseline HF and DM. Multiple HF
      related, inflammation-related and renal function-related biomarkers were
      evaluated regarding their predictive utility in new-onset DM. Incidence of DM in
      participants who developed HF was 11.8%, versus 5.4% in those who had not
      developed HF (p<0.001). Incidence of HF in participants who developed DM was
      8.5%, versus 3.8% in those who had not developed DM (p<0.001). Classical HF
      biomarkers, NT-proBNP and hs-TnT were not associated with an increased risk for
      new-onset DM. However, inflammatory biomarkers hs-CRP [hazard ratio (HR) 1.16,
      (95% CI 1.05 to 1.29), p=0.005], procalcitonin [HR 1.34, (95% CI 1.07 to 1.69),
      p=0.012] and PAI-1 [HR 1.55, (95% CI 1.37 to 1.75), p<0.001] remained
      significantly associated with new-onset DM, even after multivariable adjustment
      for established predictors of DM. CONCLUSIONS: Although HF and DM have a strong
      correlation with each other, systemic biomarkers that predict HF do not have a
      predictive value in new-onset DM. This suggests that other, indirect,
      pathophysiological mechanisms related to inflammation may explain their strong
      relation.

PMID- 29074041
TI  - Bilateral sphenopalatine ganglion block reduces blood pressure in never treated
      patients with essential hypertension. A randomized controlled single-blinded
      study.
AB  - BACKGROUND: Sympathetic fibers connect sphenopalatine ganglion (SPG) with the
      central nervous system. We aimed to study the effect of SPG block in blood
      pressure (BP) in never treated patients with stage I-II essential hypertension.
      METHODS: We performed bilateral SPG block with lidocaine 2% in 33 hypertensive
      patients (mean age 48+/-12years, 24 men) and a sham operation with water for
      injection in 11 patients who served as the control group (mean age 51+/-12years,
      8 men). All patients have been subjected to 24h ambulatory blood pressure
      monitoring prior and a month after the SBG block in order to estimate any
      differences in blood pressure parameters. We defined as responders to SBG block
      those patients with a 24h SBP decrease >=5mmHg. RESULTS: We found that 24h and
      daytime DBP (p=0.02) as well as daytime DBP load (p=0.03) were decreased in the
      study group a month after SPG block. In addition, a significant response was
      noted in 12/33 responders (36%) regarding: a. SBP and DBP during overall 24h and
      daytime (p<0.001) and night-time periods, b. pre-awake and early morning SBP and
      c. SBP (daytime and night-time) and DBP (daytime) load. No differences regarding
      BP were found in the sham operation group. CONCLUSIONS: SPG block is a promising,
      minimally invasive option of BP decrease in hypertensives, probably through SNS
      modulation. Additionally, due to its anesthetic effect, SPG block might act as a
      method of selection for those hypertensive patients with an activated SNS before
      any other invasive antihypertensive procedure.

PMID- 29074042
TI  - Crowdfunding for cardiovascular research.
AB  - The competition for public cardiovascular research grants has recently increased.
      Independent researchers are facing increasing competition for public research
      grant support and ultimately may need to seek alternative funding sources.
      Crowdfunding, a financing method of raising funds online by pooling together
      small donations from the online community to support a specific initiative, seems
      to have significant potential. However, the feasibility of crowdfunding for
      cardiovascular research remains unknown. Here, we performed exploratory data
      analysis of the feasibility of online crowdfunding in cardiovascular research.

PMID- 29074043
TI  - Change in lymphocyte to neutrophil ratio predicts acute rejection after heart
      transplantation.
AB  - AIMS: Most immunosuppressive drugs provide targeted immunosuppression by
      selective inhibition of lymphocyte activation and proliferation. This study
      evaluated whether a change in the lymphocyte to neutrophil ratio (LNR) is related
      to acute rejection. METHODS: In 74 cardiac transplant recipients peripheral blood
      lymphocyte and neutrophil counts were measured soon after (baseline) and three,
      six, and 12months after heart transplantation. The primary endpoint was the
      incidence of acute rejection. RESULTS: Significant acute rejection after heart
      transplantation occurred in 20 patients (27%) during a median follow-up of 49.4
      [IQR 37.4-61.1] months. LNR significantly increased over time (0.1149+/-0.1354 at
      baseline, 0.2330+/-0.2266 at 3months, 0.2961+/-0.2849 at 6months, and 0.3521+/
      0.2383 at 12months; P<0.001), especially during the first 3months in the group
      without acute rejection. The area under the curve of the change in LNR during the
      first three months (DeltaLNR) for acute rejection was 0.565 (95% CI 0.420 to
      0.710, P=0.380) on ROC curve analysis. The best cutoff value of Delta LNR to
      differentiate those with and without acute rejection was <=0.046 by ROC curve
      analysis. Kaplan-Meier analysis revealed that the low DeltaLNR group (<=0.046)
      had a significantly higher rate of acute rejection than the high DeltaLNR group
      (>0.046) (37.5% vs. 19.0%, log-rank: P=0.0358). The low DeltaLNR for the first
      3months was an independent predictor of clinically significant acute rejection
      after adjusting for cytomegalovirus donor seropositive and recipient
      seronegative. CONCLUSIONS: The results of this study suggest that DeltaLNR over
      the first 3months after heart transplantation is a strong and independent
      predictor of acute rejection after heart transplantation. DeltaLNR can be used as
      an early biomarker for predicting of acute rejection after heart transplantation.

PMID- 29074045
TI  - Discussion.

PMID- 29074044
TI  - DNMT1 is predictive of survival and associated with Ki-67 expression in R-CHOP
      treated diffuse large B-cell lymphomas.
AB  - DNMT1 is a target of approved anti-cancer drugs including decitabine. However,
      the prognostic value of DNMT1 protein expression in R-CHOP-treated diffuse large
      B-cell lymphomas (DLBCLs) remains unexplored. Here we showed that DNMT1 was
      expressed in the majority of DLBCL cases (n = 209/230, 90.9%) with higher
      expression in germinal centre B-cell-like (GCB)-DLBCL subtype. Low and negative
      DNMT1 expression (20% cut-off, n = 33/230, 14.3%) was predictive of worse overall
      survival (OS; p < 0.001) and progression-free survival (PFS; p < 0.001).
      Nonetheless, of the 209 DNMT1 positive patients, 33% and 42% did not achieve 5
      year OS and PFS, respectively, indicating that DNMT1 positive patients showed
      considerably heterogeneous outcomes. Moreover, DNMT1 was frequently expressed in
      mitotic cells and significantly correlated with Ki-67 or BCL6 expression (r =
      0.60 or 0.44, respectively; p < 0.001). We demonstrate that DNMT1 is predictive
      of DLBCL patients' survival, and suggest that DNMT1 could be a DLBCL therapeutic
      target due to its significant association with Ki-67.

PMID- 29074046
TI  - Mitral valve surgery in the US Veterans Administration health system: 10-year
      outcomes and trends.
AB  - OBJECTIVE: To compare mitral valve repair (MVRepair) and mitral valve replacement
      (MVReplace) trends in the Veterans Affairs (VA) Surgical Quality Improvement
      Program. METHODS: Trends were compared by bivariate analyses, followed by
      backward stepwise selection and multivariable logistic modeling to determine the
      effect of preoperative comorbidities and facility-level factors on MVRepair (vs
      MVReplace) rate. A subgroup analysis focused on patients who underwent elective
      surgery for isolated primary degenerative mitral regurgitation. Propensity
      matching was done in the overall and primary degenerative cohorts. RESULTS: From
      October 2000 to October 2013, 4165 veterans underwent MVRepair (n = 2408) or
      MVReplace (n = 1757) for MV disease of any cause at 40 VA medical centers
      (procedural volume, 0-29/y; median 7/y). The MVRepair percentage increased from
      48% in 2001 to 63% in 2013 (P < .001). MVRepair rates varied widely among
      centers; center volume explained only 19% of this variation after adjustment for
      case mix (R2 = 0.19, P = .005). Unadjusted 30-day and 1-year mortality rates were
      lower after MVRepair than after MVReplace (3.5% vs 4.8%, P = .04; 9.8% vs 12.1%,
      P = .02). Among the propensity-matched patients (n = 2520), 30-day and 1-year
      mortality were similar after MVRepair and MVReplace. In the propensity-matched
      primary degenerative subgroup (n = 664), unadjusted long-term mortality for up to
      10 years postoperatively was lower after MVRepair (28% vs 37%, P = .003), as was
      risk-adjusted long-term mortality (hazard ratio, 0.78; 95% confidence interval,
      0.61-1.01). CONCLUSIONS: In the VA Health System, mortality after MV operations
      is low. Despite the survival advantage associated with MV repair in primary
      mitral regurgitation, repair is infrequent at some centers, representing an
      opportunity for quality improvement.

PMID- 29074047
TI  - Outcomes of surgical intervention for anomalous aortic origin of a coronary
      artery: A large contemporary prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to prospectively analyze the outcomes of
      patients with anomalous aortic origin of a coronary artery undergoing surgical
      intervention according to a standardized management algorithm. METHODS: All
      patients aged 2 to 18 years undergoing surgical intervention for anomalous aortic
      origin of a coronary artery between December 2012 and April 2017 were
      prospectively included. Patients underwent stress nuclear perfusion imaging,
      stress cardiac magnetic resonance imaging, and retrospectively electrocardiogram
      gated computed tomography angiography preoperatively. Patients were cleared for
      exercise at 3 months postoperatively if asymptomatic and repeat stress nuclear
      perfusion imaging, stress cardiac magnetic resonance imaging, and computed
      tomography angiography showed normal results. RESULTS: A total of 44 patients,
      with a median age of 14 years (8-18 years), underwent surgical intervention: 9
      (20%) for the anomalous left coronary artery and 35 (80%) for the anomalous right
      coronary artery. Surgical procedures included unroofing in 35 patients (80%),
      translocation in 7 patients (16%), ostioplasty in 1 patient (2%), and side-side
      anastomosis in 1 patient (2%). One patient who presented with aborted sudden
      cardiac death from an anomalous left coronary and underwent unroofing presented 1
      year later with a recurrent episode and was found to have an unrecognized
      myocardial bridge and persistent compression of the coronary requiring
      reintervention. At last follow-up, 40 patients (91%) are asymptomatic and 4
      patients have nonspecific chest pain; 42 patients (95%) have returned to full
      activity, and 2 patients are awaiting clearance. CONCLUSIONS: Surgical treatment
      for anomalous aortic origin of a coronary artery is safe and should aim to
      associate the coronary ostium with the correct sinus, away from the intercoronary
      pillar. After surgery, the majority of patients are cleared for exercise and
      remain asymptomatic. Longer follow-up is needed to assess the true efficacy of
      surgery in the prevention of sudden cardiac death.

PMID- 29074048
TI  - Discussion.

PMID- 29074049
TI  - The dynamic cardiac biosimulator: A method for training physicians in beating
      heart mitral valve repair procedures.
AB  - OBJECTIVE: Previously, cardiac surgeons and cardiologists learned to operate new
      clinical devices for the first time in the operating room or catheterization
      laboratory. We describe a biosimulator that recapitulates normal heart valve
      physiology with associated real-time hemodynamic performance. METHODS: To
      highlight the advantages of this simulation platform, transventricular extruded
      polytetrafluoroethylene artificial chordae were attached to repair flail or
      prolapsing mitral valve leaflets. Guidance for key repair steps was by 2
      dimensional/3-dimensional echocardiography and simultaneous intracardiac
      videoscopy. RESULTS: Multiple surgeons have assessed the use of this biosimulator
      during artificial chordae implantations. This simulation platform recapitulates
      normal and pathologic mitral valve function with associated hemodynamic changes.
      Clinical situations were replicated in the simulator and echocardiography was
      used for navigation, followed by videoscopic confirmation. CONCLUSIONS: This
      beating heart biosimulator reproduces prolapsing mitral leaflet pathology. It may
      be the ideal platform for surgeon and cardiologist training on many transcatheter
      and beating heart procedures.

PMID- 29074050
TI  - Discrepancy Between European Association of Urology Guidelines and Daily Practice
      in the Management of Non-muscle-invasive Bladder Cancer: Results of a European
      Survey.
AB  - BACKGROUND: The European Association of Urology (EAU) non-muscle-invasive bladder
      cancer (NMIBC) guidelines are meant to help minimise morbidity and improve the
      care of patients with NMIBC. However, there may be underuse of guideline
      recommended care in this potentially curable cohort. OBJECTIVE: To assess
      European physicians' current practice in the management of NMIBC and evaluate its
      concordance with the EAU 2013 guidelines. DESIGN, SETTING, AND PARTICIPANTS:
      Initial 45-min telephone interviews were conducted with 20 urologists to develop
      a 26-item questionnaire for a 30-min online quantitative interview. A total of
      498 physicians with predefined experience in treatment of NMIBC patients, from
      nine European countries, completed the online interviews. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: Descriptive statistics of absolute numbers and
      percentages of the use of diagnostic tools, risk group stratification, treatment
      options chosen, and follow-up regimens were used. RESULTS AND LIMITATIONS:
      Guidelines are used by >=87% of physicians, with the EAU guidelines being the
      most used ones (71-100%). Cystoscopy (60-97%) and ultrasonography (42-95%) are
      the most used diagnostic techniques. Using EAU risk classification, 40-69% and 88
      100% of physicians correctly identify all the prognostic factors for low- and
      high-risk tumours, respectively. Re-transurethral resection of the bladder tumour
      (re-TURB) is performed in 25-75% of low-risk and 55-98% of high-risk patients.
      Between 21% and 88% of patients received a single instillation of chemotherapy
      within 24h after TURB. Adjuvant intravesical treatment is not given to 6-62%, 2
      33%, and 1-20% of the patients with low-, intermediate-, and high-risk NMIBC,
      respectively. Patients with low-risk NMIBC are likely to be overmonitored and
      those with high-risk NMIBC undermonitored. Our study is limited by the possible
      recall bias of the selected physicians. CONCLUSIONS: Although most European
      physicians claim to apply the EAU guidelines, adherence to them is low in daily
      practice. PATIENT SUMMARY: Our survey among European physicians investigated
      discrepancies between guidelines and daily practice in the management of non
      muscle-invasive bladder cancer (NMIBC). We conclude that the use of the
      recommended diagnostic tools, risk-stratification of NMIBC, and performance of re
      TURB have been adopted, but adjuvant intravesical treatment and follow-up are not
      uniformly applied.

PMID- 29074051
TI  - The inhibitory effects of beta-caryophyllene, beta-caryophyllene oxide and alpha
      humulene on the activities of the main drug-metabolizing enzymes in rat and human
      liver in vitro.
AB  - Sesquiterpenes, the main components of plant essential oils, are often taken in
      the form of folk medicines and dietary supplements. Several sesquiterpenes
      possess interesting biological activities but they could interact with
      concurrently administered drugs via inhibition of drug-metabolizing enzymes.
      Therefore, the present study was designed to test the potential inhibitory effect
      of tree structurally relative sesquiterpenes beta-caryophyllene (CAR), beta
      caryophyllene oxide (CAO) and alpha-humulene (HUM) on the activities of the main
      drug-metabolizing enzymes. For this purpose, rat and human hepatic subcellular
      fractions were incubated with CAR, CAO or HUM together with specific substrates
      for oxidation, reduction and conjugation enzymes and their coenzymes. HPLC,
      spectrophotometric and spectrofluorimetric analyses of product formations were
      used. All tested sesquiterpenes significantly inhibited cytochromes P4503A
      (CYP3A) activities in rats as well as in human hepatic microsomes, with CAO being
      the strongest inhibitor. A non-competitive type of inhibition was found. On the
      other hand, none of the tested sesquiterpenes significantly affected the
      activities of carbonyl-reducing enzymes (CBR1, AKRs, NQO1) or conjugation enzymes
      (UGTs, GSTs, SULTs, COMT). As CYP3A enzymes metabolize many drugs, their
      inhibition by CAO, CAR and HUM might affect the pharmacokinetics of concurrently
      administered drugs. Similar results obtained in rat and human hepatic microsomes
      indicate that rats could be used for further testing of possible drug
      sesquiterpenes interactions in vivo.

PMID- 29074052
TI  - Methoxsalen supplementation attenuates bone loss and inflammatory response in
      ovariectomized mice.
AB  - Methoxsalen (MTS) is a natural bioactive compound found in a variety of plants
      that has many known biofunctions; however, its effects on osteoporosis and
      related mechanisms are not clear. This study examined whether MTS exhibited
      preventive effects against postmenopausal osteoporosis. Female C3H/HeN mice were
      divided into four groups: Sham, ovariectomy (OVX), OVX with MTS (0.02% in diet),
      and OVX with estradiol (0.03 MUg/day, s.c). After 6 weeks, MTS supplementation
      significantly increased femur bone mineral density and bone surface along with
      bone surface/total volume. MTS significantly elevated the levels of serum
      formation markers (estradiol, osteocalcin and bone-alkaline phosphatase) such as
      estradiol in OVX mice. Tartrate resistant acid phosphatase staining revealed that
      MTS suppressed osteoclast numbers and formation in femur tissues compared with
      the OVX group. Supplementation of MTS slightly up-regulated osteoblastogenesis
      related genes (Runx-2, osterix, osteocalcin, and Alp) expression, whereas it
      significantly down-regulated inflammatory genes (Nfkappab and Il6) expression in
      femur tissue compared with the OVX group. These results indicate that MTS
      supplementation effectively prevented OVX-induced osteoporosis via enhancement of
      bone formation and suppression of inflammatory response in OVX mice. Our study
      provides valid scientific information regarding the development and application
      of MTS as a food ingredient, a food supplement or an alternative agent for
      preventing postmenopausal osteoporosis.

PMID- 29074053
TI  - Optimal detection of carbapenemase-producing Enterobacteriaceae from rectal
      samples: a role for enrichment?
AB  - BACKGROUND: Successful laboratory detection of carbapenemase-producing
      Enterobacteriaceae (CPE) in patient surveillance samples is a diagnostic
      challenge. In the absence of a reference standard for screening rectal swabs for
      CPE, many phenotypic, genotypic, culture- and non-culture-based assays have been
      proposed for identifying these bacteria. AIM: To develop and optimize a CPE
      screening protocol capable of identifying all frequently encountered CPE,
      including those producing OXA-48-like carbapenemases. METHODS: Faropenem
      susceptibility testing was performed on 507 presumptive CPE isolated from
      diagnostic samples and CPE rectal screens between March and August 2016. Results
      from this CPE screening method were compared to those from direct culture on
      mSuperCARBATM, temocillin enrichment culture, and use of an antibiotic resistance
      algorithm, to determine the optimal method to employ in the detection of CPE.
      FINDINGS: Faropenem was a poor predictor of carbapenemase production (58% true
      positives). The combination of a temocillin enrichment stage and interpretive
      reading of antibiotic resistance phenotypes improved the recovery and
      identification of CPE significantly (91% true positives), especially for OXA-48
      producers (P = 0.03). CONCLUSION: The combination of temocillin enrichment, a
      selective chromogenic medium, and an antibiotic resistance-based algorithm
      significantly improved the detection of all CPE recovered from routine and
      targeted surveillance samples.

PMID- 29074055
TI  - Tacrolimus Improves Symptoms of Children With Myasthenia Gravis Refractory to
      Prednisone.
AB  - BACKGROUND: Myasthenia gravis tends to affect children in China. Oral
      pyridostigmine and prednisone could effectively improve the symptoms, but
      multiple side effects become a major concern after long-term oral prednisone. To
      avoid the long-term complications of prednisone therapy and to obtain more
      satisfactory improvement, we tested the efficacy and safety of tacrolimus in
      children with myasthenia gravis. METHODS: Children with myasthenia gravis who had
      not achieved satisfactory improvement or who experienced severe side effects
      after prednisone therapy were recruited between January 2015 and December 2016 at
      Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily
      and the dose was adjusted on the basis of the clinical response and the serum
      concentration. The dosage of prednisone, the severity of symptoms, blood samples,
      the serum concentration of tacrolimus, and titers of antiacetylcholine receptor
      antibodies were evaluated every four weeks. RESULTS: Fourteen children were
      enrolled. One child withdrew two weeks after the enrollment. Thirteen children
      have completed the therapy for one year. At the end point, the dosage of
      prednisone was significantly decreased (P < 0.05), the symptoms were evaluated by
      the quantitative myasthenia gravis score, and myasthenia gravis-specific manual
      muscle testing and myasthenia gravis-activities of daily living scores were
      significantly improved (P < 0.05, P < 0.05, and P < 0.01, respectively). More
      importantly, ten (76.9%) patients had completely discontinued prednisone, and the
      major side effects were nearly reversed. The mean titer of antiacetylcholine
      receptor antibodies significantly dropped from 1.96+/-2.62 nmol/L to 0.70+/-1.04
      nmol/L (P < 0.05). No severe adverse events were reported. CONCLUSIONS: Our
      results suggest that tacrolimus is a promising agent for children with refractory
      myasthenia gravis. Randomized clinical trials are needed to confirm the
      observation.

PMID- 29074054
TI  - Temperature-controlled airflow ventilation in operating rooms compared with
      laminar airflow and turbulent mixed airflow.
AB  - AIM: To evaluate three types of ventilation systems for operating rooms with
      respect to air cleanliness [in colony-forming units (cfu/m3)], energy consumption
      and comfort of working environment (noise and draught) as reported by surgical
      team members. METHODS: Two commonly used ventilation systems, vertical laminar
      airflow (LAF) and turbulent mixed airflow (TMA), were compared with a newly
      developed ventilation technique, temperature-controlled airflow (TcAF). The cfu
      concentrations were measured at three locations in an operating room during 45
      orthopaedic procedures: close to the wound (<40cm), at the instrument table and
      peripherally in the room. The operating team evaluated the comfort of the working
      environment by answering a questionnaire. FINDINGS: LAF and TcAF, but not TMA,
      resulted in less than 10cfu/m3 at all measurement locations in the room during
      surgery. Median values of cfu/m3 close to the wound (250 samples) were 0 for LAF,
      1 for TcAF and 10 for TMA. Peripherally in the room, the cfu concentrations were
      lowest for TcAF. The cfu concentrations did not scale proportionally with airflow
      rates. Compared with LAF, the power consumption of TcAF was 28% lower and there
      was significantly less disturbance from noise and draught. CONCLUSION: TcAF and
      LAF remove bacteria more efficiently from the air than TMA, especially close to
      the wound and at the instrument table. Like LAF, the new TcAF ventilation system
      maintained very low levels of cfu in the air, but TcAF used substantially less
      energy and provided a more comfortable working environment than LAF. This enables
      energy savings with preserved air quality.

PMID- 29074056
TI  - Alice in Wonderland Syndrome: A Historical and Medical Review.
AB  - Alice in Wonderland syndrome is a disorienting neurological condition that
      affects human perception to the senses of vision, hearing, touch, sensation, and
      the phenomenon of time. Individuals affected with Alice in Wonderland syndrome
      can experience alterations in their perception of the size of objects or their
      own body parts, known as metamorphopsias. It is known to occur in conditions
      including migraine, epilepsy, and certain intoxicants and infectious diseases.
      The name refers to Lewis Carrol's well-known children's book Alice's Adventures
      in Wonderland, in which the title character experiences alterations of sensation
      in which she felt that her body had grown too tall or too small, or parts of her
      body were changing shape, size, or relationship to the rest of her body. The
      syndrome was described in 1952 by Caro Lippman, and given its name in 1955 by
      John Todd. The metamorphopsias characteristic of this condition are also
      sometimes referred to as Lilliputian hallucinations, a reference to the fictional
      island of Lilliput in the novel Gulliver's Travels, written by Jonathan Swift in
      1726. As such, many literary and medical publications have roots in the
      description of this syndrome. The purpose of this review is to summarize the
      literary and historical significance of Alice in Wonderland syndrome, as well as
      to provide the reader with a medical overview of the condition.

PMID- 29074057
TI  - Magnetoencephalographic Characteristics of Cortical Dysplasia in Children.
AB  - BACKGROUND AND RATIONALE: Magnetoencephalography has emerged as a tool for
      preoperative evaluation in children. We studied magnetoencephalography
      characteristics in subtypes of focal cortical dysplasia and correlated the
      findings with postoperative seizure outcome. METHODS: Inclusion criteria were
      children <=18 years who underwent magnetoencephalography during the preoperative
      evaluation followed by epilepsy surgery and a histopathologic diagnosis of focal
      cortical dysplasia between February 2008 and February 2013. Patient demographics,
      MRI, video electroencephalography, and magnetoencephalography data were reviewed.
      Postoperative seizure outcome data were categorized per International League
      against Epilepsy definitions. RESULTS: Of 178 magnetoencephalography studies
      performed in children during the study period, 33 patients met inclusion
      criteria. Focal cortical dysplasia type I, II, and III were found on
      histopathology in 52%, 39%, and 9% of patients, respectively. Thirty patients had
      positive magnetoencephalography dipoles, including all patients with focal
      cortical dysplasia type II and III and 82% of patients with focal cortical
      dysplasia type I. Three patients had magnetoencephalography unique spikes. Brain
      MRI lesions were noted preoperatively in 21 patients (64%). Twenty-three patients
      (77%) had surgical resection of magnetoencephalography dipoles and 11 (48%) of
      them achieved favorable outcome. CONCLUSIONS: Magnetoencephalography supplemented
      scalp electroencephalography data in spike source localization and showed unique
      spikes in 10% of the focal cortical dysplasia patients. Magnetoencephalography
      spikes and tight magnetoencephalography clusters were found more frequently in
      patients with focal cortical dysplasia type II and III as compared with focal
      cortical dysplasia type I. Presence of an MRI lesion and complete versus
      incomplete resection of magnetoencephalography cluster did not result in
      significant difference in postoperative seizure outcome, likely reflecting
      selection bias of doing magnetoencephalography in only difficult-to-localize
      epilepsies.

PMID- 29074059
TI  - Radiology and Pathology in a Child With Calcification and Simplified Gyration.

PMID- 29074058
TI  - Breastfeeding During Infancy Is Associated With a Lower Future Risk of Pediatric
      Multiple Sclerosis.
AB  - BACKGROUND: Risk of multiple sclerosis (MS) is influenced by environment and
      genetics. Infant breastfeeding appears protective against some childhood
      autoimmune disorders, but its impact on risk of MS in childhood is unknown. The
      objective of this study is to analyze the association of breastfeeding in infancy
      on future risk of pediatric-onset MS. BASIC PROCEDURES: Biological mothers of 36
      consecutive pediatric-onset MS patients completed a questionnaire on history of
      breastfeeding and various birth and demographic factors. The control group
      consisted of 72 otherwise healthy patients with a diagnosis of migraine and
      normal brain magnetic resonance imaging obtained less than 12 months before
      enrollment. Inverse probability of treatment weighting was used to reduce
      selection bias and balance the covariates between breastfed and non-breastfed
      children. MAIN FINDINGS: Demographics (with the exception of body mass index) and
      birth factors were not significantly different between groups. Whereas 36% of
      cases were breastfed, 71% of controls were breastfed (P = 0.001). The median
      duration of breastfeeding was 0 weeks (range: 0 to 40 weeks) for cases and 16
      weeks (range: 0 to 216 weeks) for controls. Lack of infant breastfeeding was
      associated with future diagnosis of pediatric-onset MS (odds ratio = 4.43; 95%
      confidence interval, 1.68 to 11.71; P = 0.003). This association remained
      significant after correcting for covariates, such as body mass index and age at
      diagnosis. CONCLUSIONS: These data demonstrate that absence of infant
      breastfeeding has an association with an increased risk of pediatric-onset MS
      diagnosis.

PMID- 29074060
TI  - Risk Factors for Cerebral Palsy in Children in Botswana.
AB  - BACKGROUND: Although cerebral palsy is reported to have a higher prevalence in
      low-resource settings, there are few studies describing risk factors for cerebral
      palsy in these settings. A better understanding of the unique risk factors
      affecting children with cerebral palsy in low-resource settings could optimize
      both resource allocation and preventative strategies. METHODS: A case-control
      study comparing children with cerebral palsy at ages two to 18 years with age
      matched healthy control subjects was conducted between 2013 and 2014 at a
      referral center in Gaborone, Botswana. Study participants were enrolled from
      inpatient and outpatient settings, and data were collected through caregiver
      interviews, review of medical records, and physical examination of subjects. Risk
      factors were evaluated using conditional logistic regression models. RESULTS: We
      studied 56 subjects with cerebral palsy and 56 age-matched control subjects.
      Significant risk factors for cerebral palsy included a history of serious
      neonatal infection (odds ratio 15.0, P = 0.009), complications during delivery
      (odds ratio 13.5, P < 0.001), and maternal human immunodeficiency virus (HIV)
      infection (odds ratio 3.5, P = 0.03). Maternal HIV infection remained a
      significant risk factor after adjusting for potential confounders and covariates
      (adjusted odds ratio 13.2, P = 0.05). CONCLUSIONS: Major risk factors for
      cerebral palsy in Botswana differ from those described in high-resource settings.
      Modifiable risk factors such as maternal HIV infection should be targeted as a
      potential strategy to reduce the incidence of cerebral palsy in Botswana. Further
      studies are necessary to determine optimal preventative and treatment strategies
      in this population.

PMID- 29074062
TI  - The role of psychological factors in the development of burning mouth syndrome.
AB  - The psychiatric profiles of 50 patients diagnosed with burning mouth syndrome
      (BMS) were compared to those of 50 age- and sex-matched individuals as the
      control group. The Symptom Checklist-90-Revised (SCL-90-R) questionnaire was used
      to evaluate the role of psychological factors in the development of BMS.
      Somatization, obsessive-compulsive, depression, anxiety, hostility, phobic
      anxiety, psychoticism, global severity index (GSI), positive symptom total (PST),
      and positive symptom distress index (PSDI) scores were significantly higher in
      the patients with BMS than in the control group. In a subgroup analysis according
      to sex, women with BMS had higher T-scores for somatization, obsessive
      compulsive, paranoid ideation, GSI, PST, and PSDI than women in the control
      group. In contrast, only the PSDI score was significantly higher in men with BMS
      compared to men in the control group. There was a significant difference in the T
      scores for somatization, psychoticism, and GSI between the three age subgroups
      (<=50, 51-65, and >=66 years). The obsessive-compulsive and PSDI scores were
      significantly higher in patients with BMS who also had at least one chronic
      disease than in patients with BMS who had no chronic disease. In conclusion,
      psychological factors are correlated with BMS.

PMID- 29074061
TI  - Anticancer Activity and Tolerance of Treatments Received Beyond Progression in
      Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel
      for Metastatic Castration-naive Prostate Cancer in the GETUG-AFU 15 Phase 3
      Trial.
AB  - BACKGROUND: Androgen deprivation therapy (ADT) plus docetaxel is the standard of
      care in fit men with metastatic castration-naive prostate cancer (mCNPC)
      following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are
      available on the efficacy of treatments used for metastatic castration-resistant
      prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.
      OBJECTIVE: To investigate the efficacy and tolerance of subsequent treatments in
      patients treated upfront with chemo-hormonal therapy for mCNPC. DESIGN, SETTING,
      AND PARTICIPANTS: Retrospective data from the GETUG-AFU 15 phase 3 trial were
      collected for treatments received for mCRPC. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: For the first three lines of salvage treatment for mCRPC we
      investigated the biochemical progression-free survival, maximum prostate-specific
      antigen (PSA) decline, overall survival, and tolerance. RESULTS AND LIMITATIONS:
      Overall, 245 patients received at least one treatment for mCRPC. For docetaxel
      used in first-line, a PSA decline >=50% was observed in 25/66 (38%) and in 4/20
      patients (20%) who had received upfront ADT alone and ADT plus docetaxel
      (p=0.14). The median biochemical progression-free survival was 6.0 mo (95%
      confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9),
      respectively. For docetaxel used in first- or second-line, a PSA decline >=50%
      was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront
      ADT alone and ADT plus docetaxel (p=0.07). PSA declines >=50% were observed with
      bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT
      alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel
      who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved
      a PSA decline >=50%. Few grade 3-4 events occurred. Study limitations include the
      observational design and retrospective characteristics of this analysis, without
      standardized therapeutic salvage protocols, and the limited number of patients in
      some of the treatment subgroups. CONCLUSIONS: Docetaxel rechallenge following
      progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only
      in a limited number of patients. Available data on abiraterone and enzalutamide
      support maintained efficacy in this setting. The lack of standardized therapeutic
      protocols for men developing mCRPC limits the comparability between patients.
      PATIENT SUMMARY: Rechallenging docetaxel at castration-resistance was active only
      in a limited number of patients treated upfront with chemo-hormonal therapy for
      metastatic castration-naive prostate cancer. Anticancer activity was suggested
      with abiraterone or enzalutamide in this setting.

PMID- 29074063
TI  - Skeletal stability following bioresorbable versus titanium fixation in
      orthognathic surgery: a systematic review and meta-analysis.
AB  - Despite developments in bioresorbable fixation over recent decades, controversy
      remains regarding skeletal stability following the use of this material in
      orthognathic surgery. This systematic review and meta-analysis investigated
      evidence from the international literature from studies comparing skeletal
      stability between bioresorbable and titanium fixation in orthognathic surgery.
      Key words were searched in MEDLINE, Embase, and Cochrane Library, and relevant
      journals and reference lists were searched for additional material, up to January
      2017. Study quality was assessed with the Newcastle-Ottawa scale. The meta
      analysis was performed using RevMan software. Ten cohort studies were included.
      The meta-analysis showed no statistically significant difference between
      bioresorbable and titanium fixation (SMD (95% CI)) for maxillary horizontal
      relapse (maxillary advancement 0.09 (-0.16 to 0.33); maxillary setback -0.04 (
      0.64 to 0.56)), maxillary vertical relapse (maxillary elongation 0.15 (-0.31 to
      0.61); maxillary impaction -0.30 (-1.10 to 0.50)), mandibular horizontal relapse
      (mandibular advancement 0.16 (-0.72 to 1.03); short-term mandibular setback -0.33
      (-0.82 to 0.15)), and mandibular angular relapse (mandibular clockwise rotation 
      0.39 (-0.79 to 0.00); mandibular counter-clockwise rotation 0.14 (-0.37 to
      0.66)). However, after mandibular setback, titanium fixation showed significantly
      less relapse in the long-term (0.97 (0.47 to 1.47)). With regard to skeletal
      stability, bioresorbable fixation is comparable to titanium fixation when used in
      maxillary setback and mandibular clockwise rotation; however titanium fixation
      may be preferable in mandibular setback. Further high-quality studies are needed
      to draw more definitive conclusions.

PMID- 29074064
TI  - The Impact of Ionospheric and Geomagnetic Changes on Mortality from Diseases of
      the Circulatory System.
AB  - We investigate the impact of solar activity changes on mortality from
      cardiovascular causes of death in the period 1994-2011 in the Czech Republic.
      This period coincides with the time of solar cycle no. 23 and the surrounding
      minima when there was an unusually low level of solar activity. We use long
      period daily time series of numbers of deaths by cause, solar activity indices
      (the relative sunspot number, and the intensity of solar radio flux), geomagnetic
      indices (Kp-the planetary index that indicates the fluctuation rate of horizontal
      components of the geomagnetic field, the Auroral Electrojet, and the disturbance
      storm time), and physical parameters describing the ionospheric effects (the
      critical frequency of the ionospheric F2 layer and the content of free electrons
      in the ionosphere). The results of the analysis confirm the hypothesis that there
      is no direct correlation between the geomagnetic solar index, Kp, and the number
      of deaths from acute myocardial infarction (code I21) or brain stroke (code I64)
      during the maxima of the solar cycle. On the other hand, the ionospheric
      parameters explain a greater part of the variability in the number of deaths for
      acute myocardial infarction or brain stroke than the model with solar parameters.
      The analysis shows that, because the values are geographically specific, the
      ionospheric parameters may describe the variability in the number of deaths from
      cardiovascular causes better than the solar indices. The cardiovascular diseases
      thus respond to the changes in the solar activity and to abnormal solar events
      indirectly through a concentration of electrical charges in the earth's
      environment.

PMID- 29074065
TI  - Plasma Glial Fibrillary Acidic Protein, Copeptin, and Matrix Metalloproteinase-9
      Concentrations among West African Stroke Subjects Compared with Stroke-Free
      Controls.
AB  - BACKGROUND: Measurement of plasma molecular markers among stroke patients has
      been proposed as an avenue for improving the accuracy of stroke diagnosis. There
      is paucity of data on the potential role of these markers in resource-limited
      settings, where the burden of stroke is greatest. OBJECTIVE: To assess the
      potential diagnostic and prognostic performance of 3 proposed biomarkers for
      stroke in a resource-constrained setting. METHODS: Consecutive stroke subjects
      presenting at a tertiary medical center in Kumasi, Ghana, with radiologically
      confirmed diagnosis and etiologic subtype information available were recruited
      along with age- and gender-matched controls in a 2:1 ratio. Plasma concentrations
      of glial fibrillary acidic protein (GFAP), copeptin, and matrix metalloproteinase
      9 (MMP-9) among stroke patients and stroke-free controls were measured in
      duplicates using enzyme linked immunoassays. Diagnostic and prognostic correlates
      were assessed using area-under-the-curve (AUC) measures of receiver operator
      curves and logistic regression analysis, respectively. RESULTS: There were 156
      stroke subjects with a mean age of 61.3 years of which 47.4% were females and 74
      age- and gender-matched stroke-free controls. Median (interquartile range) time
      from symptom onset to hospital presentation for care was 7 days (5-11).
      Diagnostic accuracy of a single measurement of the 3 biomarkers for stroke using
      AUC (95% confidence interval) plots were as follows: .84 (.77-0.91), P < .0001,
      for GFAP; .85 (.79-0.92), P < .0001, for copeptin; and .65 (.56-0.73), P = .0003,
      for MMP-9. None of the biomarkers was associated with stroke severity or
      mortality. CONCLUSION: Plasma concentrations of GFAP and copeptin demonstrated
      stronger associations with stroke occurrence in this West African cohort compared
      with controls.

PMID- 29074067
TI  - A tick-acquired red meat allergy.
AB  - Allergic reaction is a common clinical picture in the Emergency Department (ED).
      Most allergic reactions are from food or drugs. A detailed history is an integral
      aspect of determining the causative agent of an allergy. Galactose-alpha-1,3
      galactose (alpha-gal) allergy is a tick-acquired red meat allergy that causes
      delayed-onset allergic reaction or anaphylaxis due to molecular mimicry. Alpha
      gal allergy may not be widely known as a cause of allergic reactions. Lack of
      universal awareness of this phenomenon in the ED and Urgent Care setting could
      lead to misdiagnosis, or delayed diagnosis. Subsequently, lack of proper
      instruction to avoid red meat could put patients at risk for future attacks with
      morbidity or mortality. We report three cases of allergic reaction presumed from
      red meat consumption secondary to alpha-gal allergy.

PMID- 29074066
TI  - Dysphagia and Obstructive Sleep Apnea in Acute, First-Ever, Ischemic Stroke.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) and dysphagia are common in acute
      stroke and are both associated with increased risk of complications and worse
      prognosis. The aims of the present study were (1) to evaluate the prevalence of
      OSA and dysphagia in patients with acute, first-ever, ischemic stroke; (2) to
      investigate their clinical correlates; and (3) to verify if these conditions are
      associated in acute ischemic stroke. METHODS: We enrolled a cohort of 140
      consecutive patients with acute-onset (<48 hours), first-ever ischemic stroke.
      Computed tomography (CT) and magnetic resonance imaging scans confirmed the
      diagnosis. Neurological deficit was measured using the National Institutes of
      Health Stroke Scale (NIHSS) by examiners trained and certified in the use of this
      scale. Patients underwent a clinical evaluation of dysphagia (Gugging Swallowing
      Screen) and a cardiorespiratory sleep study to evaluate the presence of OSA.
      RESULTS: There are 72 patients (51.4%) with obstructive sleep apnea (OSA+), and
      there are 81 patients (57.8%) with dysphagia (Dys+). OSA+ patients were
      significantly older (P = .046) and had greater body mass index (BMI) (P = .002),
      neck circumference (P = .001), presence of diabetes (P = .013), and hypertension
      (P < .001). Dys+ patients had greater NIHSS (P < .001), lower Alberta Stroke
      Programme Early CT Score (P < .001), with greater BMI (P = .030). The association
      of OSA and dysphagia was greater than that expected based on the prevalence of
      each condition in acute stroke (P < .001). CONCLUSIONS: OSA and dysphagia are
      associated in first-ever, acute ischemic stroke.

PMID- 29074069
TI  - Performance of C-MAC videolaryngoscope for intubation in cervical spine
      immobilization conditions.

PMID- 29074070
TI  - Comparison of intubation devices in level C personal protective equipment: A
      cadaveric study.
AB  - BACKGROUND: With the advancement of chemical, biological and nuclear warfare and
      the reemergence of infectious diseases, the possibility of intubating in personal
      protective equipment has become increasingly more real to the emergency
      physician. Human cadaveric models have been found to simulate real world
      conditions better than mannequins. The aim of the study was to determine the
      first pass success rate and average time to successful intubation while wearing
      Personal Protective Equipment (PPE). Secondarily, subjects were asked to rank
      their choice of a primary and back up device, as well as the most common
      encountered barriers using PPE. METHODS: Emergency medicine residents and pre
      hospital providers were enrolled in a double randomized sequence to either
      intubation with direct laryngoscopy (DL), video laryngoscopy (VL), or the
      Supraglottic Airway Laryngopharyngeal Tube (SALT) in a cadaveric model while
      wearing level C PPE or without PPE. RESULTS: First pass success rate was 96%
      without PPE and 58% while wearing PPE when all devices were considered
      (p<=0.001). Time to intubation while wearing PPE was 35.0s while no PPE was 22.2s
      (p=0.012). While wearing PPE both DL and VL were found to allow for a faster
      intubation as compared to the SALT (23.0s and 18.8s; p=0.002 and p=0.006
      respectively). No statistical difference was noted in intubations without PPE.
      Participants indicated the most common barrier to successful intubation included
      visibility while wearing hoods (73.7%). Furthermore, 52.6% of participants
      indicated they would choose DL as the primary method to intubate with if wearing
      PPE while 47.4% would choose VL. CONCLUSION: There is a statistically significant
      difference in first pass success and time to successful intubation while wearing
      and not wearing PPE in human cadaveric models.

PMID- 29074068
TI  - An exploratory study of IV metoclopramide+diphenhydramine for acute post
      traumatic headache.
AB  - BACKGROUND: Headache is a frequent complaint among the 1.4 million patients who
      present to US emergency departments (ED) annually following trauma to the head.
      There are no evidence-based treatments of acute post-traumatic headache. METHODS:
      This was an ED-based, prospective study of intravenous (IV) metoclopramide
      20mg+diphenhydramine 25mg for acute post-traumatic headache. Patients who
      presented to our EDs with a moderate or severe headache meeting international
      criteria were enrolled and followed by telephone 2 and 7days later. The primary
      outcome was "sustained headache relief" (headache level less than "moderate" in
      the ED, no additional headache medication, and no relapse to headache worse than
      "mild").We also gathered data on associated symptomotology using the validated
      Post Concussion Symptom Scale (PCSS). RESULTS: 21 patients were enrolled. Twelve
      of 20 (60%) patients with available follow-up data reported sustained headache
      relief. All but one of the 21 enrolled patients (95%) reported improvement of
      headache to no worse than mild. Seven of 19 (37%) patients with available data
      reported moderate or severe headache during the 48h after ED discharge. One week
      later, 5/19 patients reported experiencing headaches "frequently" or "always".
      The mean Post Concussion Symptom Score improved from 47.5 (SD 29.4) before
      treatment to 10.9 (SD 14.8) at the time of ED discharge and 11.4 (SD 21.4) at one
      week after treatment. CONCLUSION: IV metoclopramide 20mg+diphenhydramine 25mg is
      an effective and well-tolerated medication regimen for patients presenting to the
      ED with acute post-traumatic headache, though 1/3 of patients report headache
      relapse after ED discharge and 1/4 of patients report persistent headaches one
      week later.

PMID- 29074071
TI  - Data acquisition workflows in liquid chromatography coupled to high resolution
      mass spectrometry-based metabolomics: Where do we stand?
AB  - Typical mass spectrometry (MS) based untargeted metabolomics protocols are
      tedious as well as time- and sample-consuming. In particular, they often rely on
      "full-scan-only" analyses using liquid chromatography (LC) coupled to high
      resolution mass spectrometry (HRMS) from which metabolites of interest are first
      highlighted, and then tentatively identified by using targeted MS/MS experiments.
      However, this situation is evolving with the emergence of integrated HRMS based
      data acquisition protocols able to perform multi-event acquisitions. Most of
      these protocols, referring to as data dependent and data independent acquisition
      (DDA and DIA, respectively), have been initially developed for proteomic
      applications and have recently demonstrated their applicability to biomedical
      studies. In this context, the aim of this article is to take stock of the
      progress made in the field of DDA- and DIA-based protocols, and evaluate their
      ability to change conventional metabolomic and lipidomic data acquisition
      workflows, through a review of HRMS instrumentation, DDA and DIA workflows, and
      also associated informatics tools.

PMID- 29074072
TI  - Transition from heterothallism to homothallism is hypothesised to have
      facilitated speciation among emerging Botryosphaeriaceae wheat-pathogens.
AB  - White grain disorder (WGD) is a recently emerged wheat disease in Australia
      caused by three Botryosphaeriaceae fungi, from the genus Eutiarosporella. These
      species are E. tritici-australis, E. darliae, and E. pseudodarliae.
      Characterisation of the mating type genes for the WGD-species show that the
      genome sequence of a single E. darliae and E. pseudodarliae isolate both harbour
      MAT1-2-1 and MAT1-1-1, which suggests that these species are homothallic.
      However, unlike most other characterised mating-type loci from other homothallic
      Dothideomycetes, these species' MAT1-1-1 are located at a separate locus,
      inserted within the coding region of another gene. The sequenced strain of E.
      tritici-australis analysed did not harbour MAT1-1-1. Including the sequenced
      strain, we screened the mating type genes present in 16 E. tritici-australis
      individuals isolated from infected grain from fields in South Australia. Of these
      16, 11 harbour MAT1-1-1 and the other five harbour MAT1-2-1. The genome of a MAT1
      1-1 harbouring isolate was re-sequenced, which demonstrated that MAT1-1-1 was
      present at the MAT locus. We examined non-coding DNA surrounding the MAT1-1-1
      gene in E. pseudodarliae and observed fragments of the MAT locus both up and
      downstream. These fragments and their orientation around MAT1-1-1 is similar to
      characterised heterothallic Botryosphaeriaceae. Based on these gene arrangements,
      we conclude that the new MAT1-1-1 containing locus likely originated from a
      cryptic DNA integration event between two heterothallic individuals. We
      hypothesise that this integration event led to the formation of a homothallic
      lineage, which is the common ancestor of E. darliae and E. pseudodarliae.

PMID- 29074073
TI  - Schizophrenia susceptibility and neuregulin signaling pathway genes: A rare
      haplotype combination based association study in Indian population.

PMID- 29074074
TI  - Potential benefit of sleep assessment prior to PTSD treatment.

PMID- 29074075
TI  - Knowledge of the Avalanche Victim Resuscitation Checklist and Utility of a
      Standardized Lecture in Italy.
AB  - INTRODUCTION: To explore baseline knowledge about avalanche guidelines and the
      Avalanche Victim Resuscitation Checklist (AVReCh) in Italy and the knowledge
      acquisition from a standardized lecture. METHODS: Standardized lecture material
      discussing AVReCh was presented during 8 mountain medicine courses from November
      2014 to April 2016 in different regions of Italy. To determine the knowledge
      acquisition from the lecture, a pre- and postlecture survey was utilized.
      RESULTS: A total of 193 surveys were analyzed. More than 50% of the participants
      had never participated in lectures/courses on avalanche guidelines, and less than
      50% of the participants knew about the AVReCh before the lecture. The correct
      temporal sequence of reportable information in the basic life support section of
      the AVReCh was selected by 40% of the participants before the lecture and by 75%
      after the lecture (P<0.001). Within subgroups analysis, most groups saw
      significant improvement in performance (P<0.05). The selection of the correct
      burial time increased from 36 to 84% (P<0.05). CONCLUSIONS: Health care providers
      and mountain rescue personnel are not widely aware of avalanche guidelines. The
      standardized lecture significantly improved knowledge of the principles of
      avalanche management related to core AVReCh elements. However, the effect that
      this knowledge acquisition has on avalanche victim survival or adherence to the
      AVReCh in the field is yet to be determined.

PMID- 29074076
TI  - Consensus nomenclature rules for radiopharmaceutical chemistry - Setting the
      record straight.
AB  - Over recent years, within the community of radiopharmaceutical sciences, there
      has been an increased incidence of incorrect usage of established scientific
      terms and conventions, and even the emergence of 'self-invented' terms. In order
      to address these concerns, an international Working Group on 'Nomenclature in
      Radiopharmaceutical Chemistry and related areas' was established in 2015 to
      achieve clarification of terms and to generate consensus on the utilisation of a
      standardised nomenclature pertinent to the field. Upon open consultation, the
      following consensus guidelines were agreed, which aim to.

PMID- 29074077
TI  - [What, how, and how much should a Family and Community Medicine resident do to
      become a good specialist?]
AB  - OBJECTIVE: To determine the ideal volume of activity to be carried out by
      residents in Family and Community Medicine in order to acquire the competencies
      of their professional activity. MATERIAL AND METHOD: The consensus opinion of a
      group of experts in the training of residents in Family and Community Medicine
      was collected from 152 tutors using an online Delphi-type questionnaire. RESULTS:
      The overall medians obtained in the different activities that should be developed
      by residents of Family and Community Medicine were: individual
      diagnostic/therapeutic interventions: retinography 60, spirometry 40,
      anticoagulation 45, cryo/electrocoagulation 35, infiltrations 45, tele
      dermatology 60, and others 45; women's health: pregnancy 45, gynaecological
      ultrasound/IUD 41, cytology 32.5, family planning 19.5, and maternal education
      17; lifestyle and care interventions: geriatrics 30, nursing 45, individual
      tobacco advice 30, group advice 15, health problems 15, and dietary advice 15;
      community intervention: sessions with youth 15, and social risk 15; training:
      sessions 40, continuing education 40. CONCLUSIONS: This information has defined
      the activity volumes that should be developed by the residents in order to
      acquire an adequate level of competence in the areas of individual diagnostic and
      therapeutic interventions, women's health, interventions to change lifestyles,
      community intervention, and clinical and training sessions. The consensus
      obtained could serve as a basis for the creation of a road map in the training of
      residents as a complementary tool to the Resident's Book, which is obligatory in
      all specialties.

PMID- 29074078
TI  - The impact of treatment accuracy on proton therapy patient selection for
      oropharyngeal cancer patients.
AB  - BACKGROUND AND PURPOSE: The impact of treatment accuracy on NTCP-based patient
      selection for proton therapy is currently unknown. This study investigates this
      impact for oropharyngeal cancer patients. MATERIALS AND METHODS: Data of 78
      patients was used to automatically generate treatment plans for a simultaneously
      integrated boost prescribing 70 GyRBE/54.25 GyRBE in 35 fractions. IMRT treatment
      plans were generated with three different margins; intensity modulated proton
      therapy (IMPT) plans for five different setup and range robustness settings. Four
      NTCP models were evaluated. Patients were selected for proton therapy if NTCP
      reduction was >=10% or >=5% for grade II or III complications, respectively.
      RESULTS: The degree of robustness had little impact on patient selection for tube
      feeding dependence, while the margin had. For other complications the impact of
      the robustness setting was noticeably higher. For high-precision IMRT (3 mm
      margin) and high-precision IMPT (3 mm setup/3% range error), most patients were
      selected for proton therapy based on problems swallowing solid food (51.3%)
      followed by tube feeding dependence (37.2%), decreased parotid flow (29.5%), and
      patient-rated xerostomia (7.7%). CONCLUSIONS: Treatment accuracy has a
      significant impact on the number of patients selected for proton therapy.
      Therefore, it cannot be ignored in estimating the number of patients for proton
      therapy.

PMID- 29074079
TI  - High dose rate brachytherapy as monotherapy for localised prostate cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate the oncological outcome of a three-implant
      high dose rate (HDR) brachytherapy (BRT) protocol as monotherapy for clinically
      localised prostate cancer. MATERIAL AND METHODS: Between February 2008 and
      December 2012, 450 consecutive patients with clinically localised prostate cancer
      were treated with HDR monotherapy. The cohort comprised of 198 low-, 135
      intermediate- and 117 high risk patients being treated with three single-fraction
      implants of 11.5Gy delivered to an intraoperative real-time, transrectal
      ultrasound defined planning treatment volume up to a total physical dose of
      34.5Gy with an interfractional interval of 21days. Fifty-eight patients (12.8%)
      received ADT, 32 of whom were high- and 26 intermediate-risk. Biochemical failure
      was defined according to the Phoenix Consensus Criteria and
      genitourinary/gastrointestinal toxicity evaluated using the Common Toxicity
      Criteria for Adverse Events version 3.0. RESULTS: The median follow-up time was
      56.3months. The 60-month overall survival, biochemical control and metastasis
      free-survival rates were 96.2%, 95.0% and 99.0%, respectively. Toxicity was
      scored per event with late Grade 2 and 3 genitourinary adverse events of 14.2%
      and 0.8%, respectively. Late Grade 2 gastrointestinal toxicity amounted 0.4% with
      no instances of Grade 3 or greater late adverse events to be reported.
      CONCLUSIONS: Our results confirm HDR BRT to be a safe and effective
      monotherapeutic treatment modality for clinically localised prostate cancer.

PMID- 29074080
TI  - Risk of complication during surgical abortion in obese women.
AB  - BACKGROUND: Surgical abortion is a generally safe procedure. Obesity is a known
      risk factor for complications in other surgical procedures, but insufficient
      information exists to determine the effects of increasing body mass index on the
      risk of surgical abortions. OBJECTIVE: The purpose of this study was to determine
      whether obesity is a risk factor for major complications in surgical abortions.
      METHODS: A quality control database from a single outpatient center was analyzed
      to determine rates of major complications during surgical abortions in relation
      to obesity class. Complications included hemorrhage, need for repeat evacuation,
      uterine perforation, cervical laceration, medication reaction, unexpected
      surgery, or unplanned admission to the hospital. Chi-squared and analysis of
      variance were used for analysis. RESULTS: We included 2468 procedures: 1475
      procedures (59.8%) in the first trimester and 993 procedures (40.2%) in the
      second trimester. The overall complications rate was 2.2%. Second-trimester
      procedures were more likely than those in the first trimester to have
      complications (3.1% vs 1.6%; P=.009). Overall, 39.6% of the women were obese, and
      9.6% of them met criteria for class 3 obesity (body mass index, >40 kg/m2). Women
      who underwent second-trimester abortions with class 3 obesity had a rate of
      complication of 8.7%, which was significantly more than normal weight women (odds
      ratio, 5.90; 95% confidence interval, 1.93-8.07; P<.001). COMMENT: Surgical
      abortions are overall safe procedures, but class 3 obesity increases the rate of
      complication in second-trimester procedures.

PMID- 29074081
TI  - Protective roles and mechanisms of Dendrobium officinal polysaccharides on
      secondary liver injury in acute colitis.
AB  - The purpose of this study was to investigate the protective roles and mechanisms
      of Dendrobium officinale polysaccharides (DOPS) on secondary liver injury in
      acute colitis. Firstly, the mice model of secondary liver injury in acute colitis
      was induced by 4% Dextran sodium sulfate (DSS). Inflammatory cell model was
      established by LPS-stimulated RAW264.7 cells. Then, the protective roles of DOPS
      were evaluated by both in vivo and in vitro experiment. The results showed that
      DOPS attenuated DSS-induced hepatic pathological damage, liver parameters,
      infiltration of macrophages, cytokines levels, MDA level and increased the
      antioxidant enzymes activities. In vitro, DOPS markedly inhibited inflammatory
      cytokines production and increased antioxidant enzymes activities. Finally, its
      molecular mechanisms were also observed. The results indicated that DOPS could
      down-regulated TNF-alpha signaling pathway and activated Nrf-2 signaling pathway
      in vivo and in vitro. These results suggested that DOPS may be an effective
      therapeutic reagent to attenuate secondary liver injury in acute colitis.

PMID- 29074082
TI  - Pullulan based oral thin film formulation of zolmitriptan: Development and
      optimization using factorial design.
AB  - The goal of study was to formulate and characterize pullulan based oral thin film
      (OTF) of zolmitriptan by solvent casting method. Based on preliminary trials,
      glass, PEG 400 and sucralose were selected as casting surface, water-miscible
      plasticizer and sweetener for OTF, respectively. A 32 factorial design was used
      to study the effect of amount of PEG 400 (X1) and sucralose (X2) as independent
      variables on tensile strength (Y1), elasticity (Y2), % in-vitro drug release in
      phosphate buffer of pH 6.8 at 5min (Q5min, Y3) and overall taste of OTF (Y4) as
      responses. OTF of batch F4 (PEG 400, 200mg; sucralose, 12mg) was identified as an
      optimized batch showing in-vitro, in-vivo disintegration time 20.70 and 21.58s,
      respectively; 95.53% Q5min; satisfactory thickness, strength, % elongation, ease
      of handling, smooth mouthfeel, excellent overall taste; even distribution of all
      ingredients in pullulan OTF (SEM study); and stable film at specified conditions
      concluding that pullulan, PEG 400 and sucralose are used in combination to make
      palatable, stable OTF of zolmitriptan.

PMID- 29074083
TI  - Anti-angiogenic activity and mechanism of a chemically sulfated natural glucan
      from Phellinus ribis.
AB  - A sulfated polysaccharide named PRP-S16 was obtained by sulfation of a glucan
      from Phellinus ribis using the chlorosulfonic acid method. PRP-S16 could
      significantly block the formation of new vessels in chicken chorioallantoic
      membrane (CAM). It could also inhibit the proliferation, migration, and tube
      formation and significantly reduced the mRNA expression of vascular endothelial
      growth factor (VEGF) in EA.hy926 endothelial cells. Western blotting indicated
      that PRP-S16 down regulated the protein expression of VEGF and VEGF receptor-1
      (VEGFR-1), and inhibited the phosphorylation of VEGFR-2, protein kinase B (Akt)
      and extracellular signal-regulated kinase (ERK1/2) in EA.hy926 cells. These
      findings suggest that the mechanism of action of the anti-angiogenesis activity
      of PRP-S16 is related to the inhibition of VEGF-induced signaling pathway. PRP
      S16 might be utilized as an effective antagonist in combating diseases associated
      with angiogenesis.

PMID- 29074084
TI  - Monitoring the protective ability of thymoquinone mixture with p-cymene against
      bovine serum albumin (BSA) glycation: MCR-ALS analysis based on combined
      spectroscopic and electrochemical methods.
AB  - Protein glycation with sugars such as glucose start by the initial reaction
      between the carbonyl group of sugars and the amino group of proteins such as
      albumin and hemoglobin. This leads to the generation of Schiff base and following
      that the amadori and advanced glycation end products (AGEs). AGEs products can
      store in tissues and blood of diabetic patients. So, they play key roles to
      generate free radicals, which cause the development of diabetes complications.
      Inhibition of protein glycation plays an important role in controlling diabetes,
      so the identification of anti-glycation compounds is now receiving considerable
      interest. In this study, the protection effects of thymoquinone and its mixture
      with p-cymene on the glycation of bovine serum albumin (BSA) have been
      investigated by differential pulse voltammetry (DPV) and UV-vis spectrophotometry
      (UV-vis) techniques. Also, the multivariate curve resolution-alternating least
      squares (MCR-ALS) method was used since the results of the experimental
      measurements have a strongly overlapping signals. Molecular docking was applied
      to determine the site specific binding of inhibitor with residues of BSA. This
      study demonstrates that thymoquinone and its mixture with p-cymene have the
      potent ability to use as a dietary adjuvant against glycation.

PMID- 29074085
TI  - Hypolipidemic effect of mannans from C. albicans serotypes a and B in acute
      hyperlipidemia in mice.
AB  - Mannans, which are biological macromolecules of polysaccharide origin and
      function as immunomodulators, have been shown to stimulate macrophages in vivo by
      interaction with the mannose receptor. Thus, they can be used to stimulate
      macrophages in order to effectively remove circulating atherogenic lipoproteins.
      Our primary aim was to evaluate the hypolipidemic potential of mannans from C.
      albicans serotype A (mannan A) and serotype B (mannan B) in a murine model of
      hyperlipidemia. Mannan A and mannan B were shown to significantly (p<0.05)
      stimulate both the proliferation (p <0.05) and nitric oxide production of murine
      peritoneal macrophages in vitro. Pre-treatment of CBA/Lac mice with mannan A
      prior to induction of hyperlipidemia significantly (p<0.001) reduced serum
      atherogenic LDL-cholesterol, total cholesterol, and triglycerides. Mannan B
      exhibited a similar, but more potent, hypolipidemic effect. Electron microscopic
      analysis of liver revealed a significant (p<0.001) decrease in the volume of
      lipid droplets when hyperlipidemic mice were pretreated by both mannans. In
      conclusion, our findings would suggest that both polysaccharide-based biological
      macromolecules evaluated in the present study, specifically, the natural
      immunomodulators (mannans A and B), appeared to function as effective lipid
      lowering macromolecules, which could potentially serve as adjunct therapy to more
      conventional hypolipidemic medications such as a statin drug.

PMID- 29074087
TI  - Corrigendum to "The ability of lipopolysaccharide (LPS) of Pasteurella multocida
      B:2 to induce clinical and pathological lesions in the nervous system of buffalo
      calves following experimental inoculation"[Microb. Pathog. 104 (2017) 340-347].

PMID- 29074086
TI  - Polyelectrolyte capsules preloaded with interconnected alginate matrix: An
      effective capsule system for encapsulation and release of macromolecules.
AB  - In recent years, the design of stimuli-responsive hollow polymeric capsules is of
      tremendous interest for the scientific community because of the broad application
      of these capsules in the biomedical field. The use of weak polyelectrolytes as
      layer components for capsule fabrication is especially interesting as it results
      in hollow capsules that show unique release characteristics under physiological
      conditions. In this work, a methodology to prepare sub-micron sized alginate
      doped calcium carbonate (CaCO3) particles through controlled precipitation in the
      presence of alginate is reported. Hollow capsules obtained by Layer-by-Layer
      (LbL) assembly of poly(allylamine hydrochloride) (PAH) and poly(methacrylic acid)
      (PMA) are showing an interconnected alginate matrix in the interior of the
      capsules. Investigations showed that the presence of alginate matrix enhances the
      encapsulation of cationic molecules (e.g. doxorubicin hydrochloride) manifold by
      charge controlled attraction mechanism. Capsule permeability investigated by
      confocal laser scanning microscopy revealed that the transformation from an open
      state to closed state is accompanied by an intermediate state where capsules are
      neither open nor closed. Furthermore, time dependent study indicated that the
      encapsulation process is linear as a function of time. The cell viability
      experiments demonstrated excellent biocompatibility of hollow capsules with mouse
      embryonic fibroblast cells. Anticancer investigations showed that DOX loaded
      capsules have significant anti-proliferative characteristics against HeLa cells.
      Such capsules have high potential for use as drug carrier for cationic drugs in
      cancer therapy.

PMID- 29074088
TI  - The American Brachytherapy Society consensus statement for accelerated partial
      breast irradiation.
AB  - PURPOSE: Adjuvant radiation after breast-conserving surgery remains the standard
      of-care treatment for patients with ductal carcinoma in situ and early-stage
      invasive breast cancer. Multiple alternatives to standard whole-breast
      irradiation exist including accelerated partial-breast irradiation (APBI).
      Therefore, the purpose of this APBI guideline is to provide updated data for
      clinicians as well as recommendations regarding appropriate patient selection and
      techniques to deliver APBI. METHODS: Members of the American Brachytherapy
      Society with expertise in breast cancer and breast brachytherapy in particular
      created an updated guideline for appropriate patient selection based on an
      extensive literature search and clinical experience. In addition, data were
      evaluated with respect to APBI techniques and recommendations presented. RESULTS:
      Appropriate candidates for APBI include patients aged 45 years or older, all
      invasive histologies and ductal carcinoma in situ, tumors 3 cm or less, node
      negative, estrogen receptor positive/negative, no lymphovascular space invasion,
      and negative margins. With respect to techniques, the strongest evidence is for
      interstitial brachytherapy and intensity-modulated radiation therapy APBI with
      moderate evidence to support applicator brachytherapy or three-dimensional
      conformal radiotherapy APBI. Intraoperative radiation therapy and electronic
      brachytherapy should not be offered regardless of technique outside of clinical
      trial. CONCLUSIONS: The updated guidelines presented offer clinicians with a
      summary of data supporting APBI and guidelines for the appropriate and safe
      utilization of the technique.

PMID- 29074089
TI  - Application of next-generation sequencing to detect acyclovir-resistant herpes
      simplex virus type 1 variants at low frequency in thymidine kinase gene of the
      isolates recovered from patients with hematopoietic stem cell transplantation.
AB  - Ion Torrent next-generation sequencing (NGS) technology was applied to study the
      mode of emergence of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1
      (HSV-1) in patients with hematopoietic stem cell transplantation (HSCT) by
      quantitatively detecting mutations in the viral thymidine kinase (vTK) gene in
      the HSV-1 isolates recovered from HSCT patients. All of the mutations detected
      with the Sanger sequencing method in the vTK genes of HSV-1 isolates were also
      detected with the NGS assay. Furthermore, different mutations, which conferred
      ACV resistance and were not detected with the Sanger sequencing method, were also
      detected in a quantitative manner by using the NGS assay. The approach described
      here is applicable to studying the emergence process of vTK gene mutation
      associated ACVr HSV-1 more in detail than the Sanger method. The NGS assay makes
      it possible to make a diagnosis of vTK gene mutation-associated ACVr HSV-1
      infections at the early stage, which the ratio of ACVr HSV-1 is much lower than
      that of ACV-sensitive (ACVs) HSV-1.

PMID- 29074090
TI  - The role of a single gene encoding the Single von Willebrand factor C-domain
      protein (SVC) in bumblebee immunity extends beyond antiviral defense.
AB  - The Single von Willebrand factor C-domain proteins (SVCs) are a group of short
      proteins mainly found in arthropods. They are proposed to be responsive in
      relation to environmental challenges including the nutritional status, bacterial
      and viral infections. The SVC protein Vago acts as a cross-talk molecule between
      the small interfering RNA (siRNA) pathway and the Jak/STAT pathway upon viral
      infection in Drosophila melanogaster and Culex mosquito cells. Unlike flies and
      mosquitoes that possess diverse SVCs, most bee species only have one of which the
      function remains unclear. Here we investigated whether this single SVC within the
      genome of the bumblebee Bombus terrestris is also involved in the host antiviral
      immunity and whether links with other immune pathways can be found. We can show
      the presence of two key characteristics of Vago linked with the single SVC in B.
      terrestris (BtSVC). The antiviral character is proven by silencing BtSVC, which
      lead to increased Israeli acute paralysis virus (IAPV) levels in the fat body.
      Second, the silencing of BtDicer-2 resulted in a lower expression of BtSVC and
      increased IAPV levels, confirming the link between Dicer-2 and BtSVC. We were,
      however, unable to demonstrate a third known role of Vago in the activation of
      the Jak/STAT pathway. This is probably because we lack good markers for this
      pathway in bumblebees. Interestingly, we found that BtSVC contributes to the
      basal expression levels of four antimicrobial peptide (AMP)-coding genes in the
      fat body of the bumblebees. Therefore, the single SVC gene in bumblebees may be
      involved in both host antiviral immunity and basal AMPs expression.

PMID- 29074092
TI  - Eosinophilic Esophagitis: Crepe Paper-Like Appearance.

PMID- 29074091
TI  - Fibroblast growth factor 23 in patients with acute dyspnea: Data from the
      Akershus Cardiac Examination (ACE) 2 Study.
AB  - BACKGROUND: Circulating fibroblast growth factor 23 (FGF23) concentrations have
      been linked to left ventricular remodeling and unfavorable cardiovascular
      outcomes, but whether FGF23 is associated with heart failure (HF) diagnosis and
      outcome in unselected patients with dyspnea is unknown. Accordingly, we assessed
      the diagnostic and prognostic properties of FGF23 in patients presenting to the
      emergency department with acute dyspnea. METHODS AND RESULTS: FGF23 was measured
      in 314 patients admitted with acute dyspnea and the diagnostic and prognostic
      merit was compared to that of N-terminal pro-B-type natriuretic peptide (NT
      proBNP). The diagnosis of acute HF was adjudicated by two independent physicians.
      Circulating FGF23 concentrations on hospital admission were higher in patients
      with acute HF vs. patients with non-HF related dyspnea: median 3.60 (IQR 1.24
      8.77) vs. 1.00 (0.43-2.20) pmol/L; P<0.001. The receiver-operating statistics
      area under the curve for acute HF diagnosis was 0.750 (0.699-0.797) for FGF23 and
      0.853 (0.809-0.890) for NT-proBNP. Adjusting for clinical risk indices and
      cardiac biomarkers in multivariate Cox regression analysis, admission FGF23
      concentrations were associated with mortality in the total study population
      (hazard ratio [HR] per 1 SD in lnFGF23 1.74 [1.40-2.16]). FGF23 also reclassified
      patients into their correct risk strata on top of clinical variables
      significantly associated with outcomes in the total cohort (net reclassification
      index 0.386 [0.161-0.612]). In patients with acute HF, both admission FGF23 and
      NT-proBNP concentrations were associated with mortality. CONCLUSION: Circulating
      FGF23 concentrations provide incremental prognostic information to established
      risk indices in patients with acute dyspnea, but do not improve diagnostic
      accuracy over NT-proBNP measurements.

PMID- 29074093
TI  - A New HOPE? Lessons from Heart Outcomes Prevention Evaluation-3.
AB  - Lifestyle modification is the cornerstone of preventing atherosclerotic
      cardiovascular disease. When this is not sufficient in reducing risk, statin
      therapy is first line. Heart Outcomes Prevention Evaluation (HOPE-3) was a
      randomized controlled trial of rosuvastatin versus placebo, which demonstrated a
      significant net benefit in a lower-risk population without known atherosclerotic
      cardiovascular disease. There were many novel characteristics about this trial
      that should not be overlooked. It contained a diverse population and was the
      first trial to base inclusion solely on easily ascertainable metabolic risk
      factors. It had high adherence in the statin arm, likely due to several factors,
      including a run-in phase, close follow-up, and low intolerance of moderate-dose
      rosuvastatin. Attempting to simulate these could increase adherence among clinic
      populations. Although HOPE-3 did not demonstrate a significant decrease in
      cardiovascular events among women, meta-analysis including prior randomized
      controlled trials still demonstrates significant benefit, supporting prior
      guidelines for statin therapy in this group. Finally, HOPE-3 provides data that
      potentially support the legacy effect of statins. Understanding these key points
      provides additional insight into the benefits of statin therapy.

PMID- 29074094
TI  - An Approach to Myopathy for the Primary Care Clinician.
AB  - Patients with muscle weakness are frequently encountered in the primary care
      clinic; however, the identification of an underlying disorder of muscle can pose
      a significant challenge. The aim of this review article is to provide a clinical
      and diagnostic framework to aid the primary care clinician in the detection and
      evaluation of suspected myopathies.

PMID- 29074095
TI  - The Midnight Bite! A Kissing Bug Nightmare.

PMID- 29074096
TI  - Modeling the impact of the human activity, behavior and decisions on the
      environment. Marketing and green consumer (Special Issue).

PMID- 29074097
TI  - Behavioral effects of early life maternal trauma witness in rats.
AB  - BACKGROUND: Earlier, we have reported that post-traumatic stress disorder (PTSD)
      like behaviors developed in rats that witnessed their cage mates undergo repeated
      traumatic stress. More recently, we published that early life physical traumatic
      stress leads to later life depression-like behaviors in rats. Whether early life
      trauma witness causes later life PTSD-like behaviors is not known. Also unclear
      are sex-specific stress-induced behavioral variations in later life. The early
      life witness component of stress is an important aspect of stress-induced
      psychopathologies and must be investigated. OBJECTIVE: Here, we have examined the
      impact of early life repeated witnessing of traumatic events by pups from post
      natal day (PND) 21-PND27, on later life behaviors at PND60, and the behavioral
      impact of postpartum traumatic stress in female rats. METHODS: We used a modified
      version of rodent social defeat model to induce postpartum stress in female rats
      and trauma witness stress in pups. One female Sprague-Dawley rat (intruder) was
      introduced into the cage of an aggressive Long-Evans male rat (resident). The
      encounter between the two resulted in attacks between the female rat and the Long
      Evans male rat. Three exposures of social defeat (attacks) were given for 7
      consecutive days. The social defeat traumatic events were witnessed by 6 pups
      (offspring of the intruder female rat, PND21-27), placed in six separate
      enclosures surrounding the cage. The objective of this experiment was three-fold:
      1) to test later life behavioral effects in pups from witnessing maternal defeat,
      2) to examine gender susceptibility of pups in maternal defeat witness-induced
      behaviors, 3) to test behavioral effect in female rats 24h after receiving the
      last social defeat exposure. RESULTS: We observed that while anxiety-like
      behavior assessed in open-field and elevated plus-maze tests, was not affected in
      male or female rats upon witnessing repeated maternal traumatic stress,
      depression-like behavior in forced-swim test was observed at PND60 in both male
      and female rats, with greater effect in male rats. No change was observed in
      learning and memory functions using radial arm water maze test in both male and
      female rats. Interestingly, socially defeated female rats (dams: mother of the
      pups) developed both anxiety and depression-like behavior with no change in
      learning-memory function when compared to control female rats. CONCLUSIONS: Our
      findings suggest that early life maternal stress witness history leads to
      depression-like behavior in both male and female adult rats, and dams developed
      both anxiety and depression-like behaviors.

PMID- 29074098
TI  - Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an
      international, multicentre, open-label, single-arm first-in-man phase 1 trial.
AB  - BACKGROUND: Most patients with anaplastic lymphoma kinase (ALK)-rearranged or ROS
      proto-oncogene 1 (ROS1)-rearranged non-small-cell lung cancer (NSCLC) are
      sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably
      develops, commonly within the CNS. This study aimed to analyse the safety,
      efficacy, and pharmacokinetic properties of lorlatinib, a novel, highly potent,
      selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against
      most known resistance mutations, in patients with advanced ALK-positive or ROS1
      positive NSCLC. METHODS: In this international multicentre, open-label, single
      arm, first-in-man phase 1 dose-escalation study, eligible patients had advanced
      ALK-positive or ROS1-positive NSCLC and were older than 18 years, with an Eastern
      Cooperative Oncology Group performance status of 0 or 1, and adequate end-organ
      function. Lorlatinib was administered orally to patients at doses ranging from 10
      mg to 200 mg once daily or 35 mg to 100 mg twice daily, with a minimum of three
      patients receiving each dose. For some patients, tumour biopsy was done before
      lorlatinib treatment to identify ALK resistance mutations. Safety was assessed in
      patients who received at least one dose of lorlatinib; efficacy was assessed in
      the intention-to-treat population (patients who received at least one dose of
      study treatment and had either ALK or ROS1 rearrangement). The primary endpoint
      was dose-limiting toxicities during cycle 1 according to investigator assessment;
      secondary endpoints included safety, pharmacokinetics, and overall response. This
      study is ongoing and is registered with ClinicalTrials.gov, number NCT01970865.
      FINDINGS: Between Jan 22, 2014, and July 10, 2015, 54 patients received at least
      one dose of lorlatinib, including 41 (77%) with ALK-positive and 12 (23%) with
      ROS1-positive NSCLC; one patient had unconfirmed ALK and ROS1 status. 28 (52%)
      patients had received two or more TKIs, and 39 (72%) patients had CNS metastases.
      The most common treatment-related adverse events among the 54 patients were
      hypercholesterolaemia (39 [72%] of 54 patients), hypertriglyceridaemia (21 [39%]
      of 54 patients), peripheral neuropathy (21 [39%] of 54 patients), and peripheral
      oedema (21 [39%] of 54 patients). One dose-limiting toxicity occurred at 200 mg
      (the patient did not take at least 16 of 21 prescribed total daily doses in cycle
      1 because of toxicities attributable to study drug, which were grade 2
      neurocognitive adverse events comprising slowed speech and mentation and word
      finding difficulty). No maximum tolerated dose was identified. The recommended
      phase 2 dose was selected as 100 mg once daily. For ALK-positive patients, the
      proportion of patients who achieved an objective response was 19 (46%) of 41
      patients (95% CI 31-63); for those who had received two or more TKIs, the
      proportion of patients with an objective response was 11 (42%) of 26 patients (23
      63). In ROS1-positive patients, including seven crizotinib-pretreated patients,
      an objective response was achieved by six (50%) of 12 patients (95% CI 21-79).
      INTERPRETATION: In this phase 1, dose-escalation study, lorlatinib showed both
      systemic and intracranial activity in patients with advanced ALK-positive or ROS1
      positive NSCLC, most of whom had CNS metastases and had previously had two or
      more TKI treatments fail. Therefore, lorlatinib might be an effective therapeutic
      strategy for patients with ALK-positive NSCLC who have become resistant to
      currently available TKIs, including second-generation ALK TKIs, and is being
      investigated in a phase 3 randomised controlled trial comparing lorlatinib to
      crizotinib (ClinicalTrials.gov, NCT03052608). FUNDING: Pfizer.

PMID- 29074100
TI  - ALK and ROS1 rearrangement in NSCLC: rapidly evolving standards.

PMID- 29074101
TI  - Towards personalised medicine in lung and thymus neuroendocrine tumours.

PMID- 29074099
TI  - Efficacy and safety of long-acting pasireotide or everolimus alone or in
      combination in patients with advanced carcinoids of the lung and thymus (LUNA):
      an open-label, multicentre, randomised, phase 2 trial.
AB  - BACKGROUND: There are no data from prospective studies focused exclusively on
      patients with advanced lung and thymic carcinoids. We aimed to assess the
      efficacy and safety of long-acting pasireotide and everolimus, administered alone
      or in combination, in patients with advanced carcinoids of the lung or thymus.
      METHODS: LUNA was a prospective, multicentre, randomised, open-label, phase 2
      trial of adult patients (aged >18 years) with advanced (unresectable or
      metastatic), well differentiated carcinoid tumours of the lung or thymus, with
      radiological progression within 12 months before randomisation, and a WHO
      performance status of 0-2. At each centre, the investigator or their designee
      registered each patient using an interactive voice recognition system into one of
      the three treatment groups. The randomisation allocation sequence was generated
      by an external company; patients were randomly assigned (1:1:1) to receive
      treatment with long-acting pasireotide (60 mg intramuscularly every 28 days),
      everolimus (10 mg orally once daily), or both in combination, for the core 12
      month treatment period. Patients were stratified by carcinoid type (typical vs
      atypical) and line of study treatment (first line vs others). The primary
      endpoint was the proportion of patients progression-free at month 9, defined as
      the proportion of patients with overall lesion assessment at month 9 showing a
      complete response, partial response, or stable disease according to local
      Response Evaluation Criteria in Solid Tumors, version 1.1, assessed in the
      intention-to-treat population. Safety was assessed in all patients who received
      at least one dose of study drug and had at least one post-baseline safety
      assessment. The trial is registered with ClinicalTrials.gov, number NCT01563354.
      The extension phase of the study is ongoing. FINDINGS: Between Aug 16, 2013, and
      Sept 30, 2014, 124 patients were enrolled from 36 centres in nine countries: 41
      were allocated to the long-acting pasireotide group, 42 to the everolimus group,
      and 41 to the combination group. At month 9, the proportion of patients with an
      overall lesion assessment of complete response, partial response, or stable
      disease was 16 of 41 patients (39.0%, 95% CI 24.2-55.5) in the long-acting
      pasireotide group, 14 of 42 patients (33.3%, 19.6-49.5) in the everolimus group,
      and 24 of 41 patients (58.5%, 42.1-73.7) in the combination group. The most
      common grade 1-2 adverse events with a suspected association with long-acting
      pasireotide monotherapy were diarrhoea (15 [37%] of 41), hyperglycaemia (17
      [41%]), and weight loss (8 [20%]); those with a suspected association with
      everolimus monotherapy were stomatitis (26 [62%] of 42) and diarrhoea (16 [38%]);
      and those suspected to be associated with combination treatment were
      hyperglycaemia (27 [66%] of 41]), diarrhoea (19 [46%]), and asthenia (8 [20%]).
      The most common grade 3-4 adverse events with a suspected association with long
      acting pasireotide monotherapy were gamma-glutamyltransferase increased (four
      [10%] of 41 patients), diarrhoea (three [7%]), and hyperglycaemia (three [7%]);
      those for everolimus were hyperglycaemia (seven [17%] of 42 patients), stomatitis
      (four [10%]), and diarrhoea (three [7%]); those for combination treatment were
      hyperglycaemia (nine [22%] of 41 patients) and diarrhoea (four [10%]). 11
      patients died during the core 12-month treatment phase or up to 56 days after the
      last study treatment exposure date: two (5%) of 41 in the long-acting pasireotide
      group, six (14%) of 42 in the everolimus group, and three (7%) of 41 in the
      combination group. No deaths were suspected to be related to long-acting
      pasireotide treatment. One death in the everolimus group (acute kidney injury
      associated with diarrhoea), and two deaths in the combination group (diarrhoea
      and urinary sepsis in one patient, and acute renal failure and respiratory
      failure in one patient) were suspected to be related to everolimus treatment. In
      the latter patient, acute renal failure was not suspected to be related to
      everolimus treatment, but respiratory failure was suspected to be related.
      INTERPRETATION: The study met the primary endpoint in all three treatment groups.
      Safety profiles were consistent with the known safety profiles of these agents.
      Further studies are needed to confirm the antitumour efficacy of the combination
      of a somatostatin analogue with everolimus in lung and thymic carcinoids.
      FUNDING: Novartis Pharma AG.

PMID- 29074102
TI  - Adherence to HIV post-exposure prophylaxis: A multivariate regression analysis of
      a 5 years prospective cohort.
AB  - BACKGROUND: Non-occupational post-exposure prophylaxis (nPEP) is a recommended
      public health intervention after a sexual or percutaneous exposure to human
      immunodeficiency virus (HIV). METHODS: We conducted a prospective observational
      study recording consultations for nPEP at a reference HIV center in Brussels,
      Belgium from January 2011 to December 2015. We recorded attendance to follow-up,
      reported completion of nPEP and pharmacy records to measure adherence.
      Multivariate logistic regressions were performed to identify independent risk
      factors for adherence to nPEP and attendance to first follow-up visit at the STI
      clinic. FINDINGS: Among 1881 patients receiving nPEP, 66.4% had a documented
      completion of a 28-day course of nPEP and 87.3% attended their first follow-up
      clinic visit. MSM (OR, 1.40; 95%CI, 1.04-1.90), being a native Belgian (OR, 1.50;
      95%CI, 1.18-1.90), older age (OR, 1.02; 95%CI, 1.01-1.04), being a sexual assault
      survivor (OR, 0.59; 95%CI, 0.38-0.91), having had a previous nPEP treatment (OR,
      1.44; 95%CI, 1.02-2.02), consultation during daytime (OR, 1.35; 95%CI, 1.07-1.70)
      and benefitting from a health insurance (OR, 2.11; 95%CI, 1.58-2.89) were
      significant independent predictors for adherence to nPEP. Patients whose initial
      treatment was AZT/3TC/IDV/r had similar adherence than patients on d4T/3TC/LPV/r
      (OR, 0.898; 95%CI, 0.68-1.20). INTERPRETATION: Multiple independent risk factors
      for nPEP retention into care and adherence are present at treatment initiation
      and might be targeted by tailored interventions. Sexual assault victims are
      overexposed to deleterious consequences of the lack of health insurance on
      compliance.

PMID- 29074103
TI  - Molecular identification and functional analysis of two variants of myeloid
      differentiation factor 88 (MyD88) from disk abalone (Haliotis discus discus).
AB  - Myeloid differentiation factor 88 (MyD88) is a crucial adaptor protein of the
      Toll-like receptor (TLR)- and interleukin 1 receptor-mediated signaling pathways
      and is involved in a diverse array of inflammatory responses via NF-kappaB
      activation. In the present study, two MyD88 variants were identified from disk
      abalone (Haliotis discus discus) and designated AbMyD88-2 and AbMyD88-X. The
      deduced AbMyD88-2 and AbMyD88-X comprised 433 and 354 amino acids with predicted
      molecular masses of 48.85 kDa and 40.17 kDa, respectively. AbMyD88-2 and AbMyD88
      X possessed typical MyD88 domain structural features including an N-terminal
      death domain (DD) and C-terminal toll interleukin 1 receptor (TIR) domain similar
      to those in mammals. Expression analysis of AbMyD88-2 and AbMyD88-X mRNA at
      different early embryonic developmental stages of abalone by qPCR revealed that
      their constitutive expression at all developmental stages analyzed with the
      considerably higher values at the 16-cell (AbMyD88-2) and morula stages (AbMyD88
      X). In unchallenged disk abalones, AbMyD88-2 was highly expressed in muscles,
      while AbMyD88-X mRNA was predominantly transcribed in hemocytes. Moreover,
      AbMyD88-2 and AbMyD88-X mRNA were differentially modulated in abalone hemocytes
      after a challenge with live bacteria (Vibrio parahaemolyticus, Listeria
      monocytogenes), virus (viral hemorrhagic septicemia virus), and pathogen
      associated molecular patterns (lipopolysaccharides and Poly I:C). Overexpression
      of AbMyD88-2 and AbMyD88-X in HEK293T cells induced the activation of the NF
      kappaB promoter. AbMyD88-2 and AbMyD88-X involvement in inflammatory responses
      was characterized by their overexpression in RAW264.7 murine macrophage cells.
      These results revealed comparatively higher NO (Nitric oxide) production,
      induction of inflammatory mediator genes (iNOS and COX2), and proinflammatory
      genes (IL1beta, IL6 and TNFalpha) expression in abalone MyD88s-overexpressing
      cells than in mock control in the presence or absence of LPS stimulation.
      Altogether, these results suggest that existence of a MyD88-dependent like
      signaling pathway in disk abalone and that both AbMyD88-2 and AbMyD88-X might be
      involved in innate immune and inflammatory responses.

PMID- 29074104
TI  - The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt
      overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM
      cells.
AB  - Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging
      evidence demonstrates the important role of autophagy in cancer cell resistance
      to chemotherapy. Therefore, autophagy inhibition by natural compounds may be a
      promising strategy for overcoming drug resistance in liver cancer cells. Here, we
      found that ADCX, a natural cycloartane triterpenoid extracted from the
      traditional Chinese medicine (TCM) source Cimicifugae rhizoma (Shengma), impaired
      autophagic degradation by suppressing lysosomal cathepsin B (CTSB) expression in
      multidrug-resistant liver cancer HepG2/ADM cells, thereby leading to autophagic
      flux inhibition. Moreover, impairing autophagic flux promoted ADCX-induced
      apoptotic cell death in HepG2/ADM cells. Interestingly, Akt was overactivated by
      ADCX treatment, which downregulated CTSB and inhibited autophagic flux. Together,
      our results provide the first demonstration that an active TCM constituent can
      overcome multidrug resistance in liver cancer cells via Akt-mediated inhibition
      of autophagic degradation.

PMID- 29074105
TI  - Endogenous hydrogen sulfide regulates histone demethylase JMJD3-mediated
      inflammatory response in LPS-stimulated macrophages and in a mouse model of LPS
      induced septic shock.
AB  - Overproduction of inflammatory mediators contributes to uncontrolled inflammation
      during endotoxin shock. Cystathionine-gamma-lyase (CSE), an enzyme involved in
      hydrogen sulfide (H2S) biosynthesis, has potential anti-inflammatory activity in
      a variety of inflammatory diseases. Jumonji domain-containing protein 3 (JMJD3),
      a histone 3 Lys27 (H3K27) demethylase, has been implicated in macrophage
      activation, but its function in CSE-mediated anti-inflammatory activities remains
      unknown. In the present study CSE was found to be upregulated in macrophages and
      mouse lipopolysaccharide (LPS) challenge models. LPS stimulation also enhanced
      the activation of JMJD3 and decreased H3K27me3 levels. JMJD3 knockdown
      upregulated H3K27me3 levels and attenuated the LPS-mediated inflammatory
      response. CSE knockout amplified the inflammatory cascade by increasing JMJD3
      expression in septic mice. Similarly, enhanced production of inflammatory
      mediators by macrophages was mitigated by CSE overexpression via inhibition of
      JMJD3 expression. This is the first report indicating that inflammation enhanced
      CSE/H2S system biosynthesis, that in turn attenuated the LPS-triggered
      inflammatory response by regulating JMJD3 expression. Thus, the CSE/H2S system
      represents an epigenetic-based modification mechanism to prevent uncontrolled
      inflammation.

PMID- 29074106
TI  - Role of endogenous and exogenous nitric oxide, carbon monoxide and hydrogen
      sulfide in HCT116 colon cancer cell proliferation.
AB  - The role of the three gasotransmitter systems - nitric oxide (NO), carbon
      monoxide (CO) and hydrogen sulfide (H2S) - in cancer cells has not yet been
      studied simultaneously in the same experimental system. We measured the
      expression of NO and CO and H2S generating enzymes in primary colon cancer
      tissues and HCT116 colon cancer cells, and evaluated the effect of their
      pharmacological inhibition or pharmacological donation on cell proliferation.
      Increased expression of iNOS, nNOS, HO-1, CBS and 3-MST was detected in colon
      cancer. Inhibitors of NOS, HO-1/2, CBS/CSE and 3-MST, at lower concentrations,
      slightly stimulated HCT116 cell proliferation, but inhibited proliferation at
      higher concentrations. Donors of NO, CO or H2S inhibited HCT116 proliferation in
      a concentration-dependent manner. Inhibition of the cGMP/VASP pathway, Akt and
      p44/42 MAPK (Erk1/2) inhibited HCT116 cell proliferation. Endogenous NO and H2S
      biosynthesis were found to play a role in the maintenance of the activity of the
      cGMP/VASP pathway in HCT116 cells. We conclude that each of the three
      gasotransmitters play similar, bell-shaped roles in the control of HCT116 cell
      proliferation: endogenously produced NO, CO and H2S, at an optimal concentration,
      support HCT116 proliferation; inhibition of their production (which decreases
      gasotransmitter levels below optimal concentrations) as well as exogenous
      delivery of these gasotransmitters (which increases gasotransmitter levels above
      optimal concentrations) suppresses colon cancer cell proliferation. The current
      data give a mechanistic explanation for the paradoxical finding that both
      inhibitors and donors of NO, CO and H2S exert anticancer actions in cancer cells.

PMID- 29074107
TI  - Risk factors for presence and severity of pulmonary embolism in patients with
      deep venous thrombosis.
AB  - OBJECTIVE: The Caprini model estimates patients' risk for venous thromboembolism
      by 30 different factors. Hemodynamically significant pulmonary embolism (PE),
      defined as high-risk (massive) or intermediate-risk (submassive) PE, has high
      morbidity and mortality rates. This study tests whether the Caprini model and
      deep venous thrombosis (DVT) characteristics correlate with the prevalence of PE
      and hemodynamically significant PE in patients with DVT. METHODS: A retrospective
      review of patients diagnosed with DVT between January 2013 and August 2014 in a
      tertiary care center was performed. Multivariable analysis was used to determine
      predictors of PE and hemodynamically significant PE. RESULTS: Of 838 consecutive
      patients with DVT, 217 (25.9%) had concomitant PE at presentation, of whom 135
      had hemodynamically significant PE (101 submassive PE, 34 massive PE). The mean
      age was 65 years, and 51.0% were women. There was no significant relation between
      age or gender and the occurrence of PE or hemodynamically significant PE.
      Patients with PE were less likely to have undergone recent surgery (18.4% vs
      30.3%; P = .001), to have sepsis (4.6% vs 11.8%; P = .002), and to have higher
      Caprini scores (6.1 vs 6.5; P = .047). Patients with DVT were less likely to have
      hemodynamically significant PE after recent surgery (13.3% vs 27.2%; P = .011)
      but more likely to have hemodynamically significant PE with proximal DVT (80.7%
      vs 64.2%). There was no association between Caprini score and hemodynamically
      significant PE (6.3 vs 5.7; P = .171). CONCLUSIONS: The Caprini model has a poor
      association with PE or hemodynamically significant PE in patients with DVT. Among
      all patients with DVT, a concomitant diagnosis of PE or hemodynamically
      significant PE is less common in those with sepsis or undergoing recent surgery
      but more common in those with proximal DVT.

PMID- 29074108
TI  - Crystallographic and enzymatic insights into the mechanisms of Mg-ADP inhibition
      in the A1 complex of the A1AO ATP synthase.
AB  - F-ATP synthases are described to have mechanisms which regulate the unnecessary
      depletion of ATP pool during an energy limited state of the cell. Mg-ADP
      inhibition is one of the regulatory features where Mg-ADP gets entrapped in the
      catalytic site, preventing the binding of ATP and further inhibiting ATP
      hydrolysis. Knowledge about the existence and regulation of the related archaeal
      type A1AO ATP synthases (A3B3CDE2FG2ac) is limited. We demonstrate MgADP
      inhibition of the enzymatically active A3B3D- and A3B3DF complexes of
      Methanosarcina mazei Go1 A-ATP synthase and reveal the importance of the amino
      acids P235 and S238 inside the P-loop (GPFGSGKTV) of the catalytic A subunit.
      Substituting these two residues by the respective P-loop residues alanine and
      cysteine (GAFGCGKTV) of the related eukaryotic V-ATPase increases significantly
      the ATPase activity of the enzyme variant and abolishes MgADP inhibition. The
      atomic structure of the P235A, S238C double mutant of subunit A of the Pyrococcus
      horikoshii OT3 A-ATP synthase provides details of how these critical residues
      affect nucleotide-binding and ATP hydrolysis in this molecular engine. The
      qualitative data are confirmed by quantitative results derived from fluorescence
      correlation spectroscopy experiments.

PMID- 29074110
TI  - Evaluation of a new model of hind limb ischemia in rabbits.
AB  - OBJECTIVE: Various animal models of critical limb ischemia have been developed in
      the past. However, there is no animal model that can undergo endovascular
      treatment, while providing reproducible true critical limb ischemia with arterial
      ulcers and rest pain. We evaluated the efficacy of a new model of rabbit hindlimb
      ischemia created through a percutaneous approach using embolization with
      calibrated particles. METHODS: Through a percutaneous transauricular artery
      approach and selective catheterization of the superficial femoral artery,
      embolization of distal limb vessels was performed using a mixture of 300- to 500
      MUm calibrated microparticles (Embosphere, Merit Medical, Salt Lake City, Utah),
      saline solution, and iodine contrast. Clinical and ultrasound imaging-based blood
      flow evaluation was performed before embolization and during follow-up.
      Histologic evaluation was performed at humane killing 14 days after the
      procedure. RESULTS: The model was successfully created in 10 rabbits (10 limbs).
      One rabbit died of sudden death at 8 days after the procedure. The nine surviving
      rabbits developed hind ulcers. All rabbits had a higher pain score in the follow
      up compared to baseline value (P < .0001). Blood flow in the saphenous artery
      decreased significantly after the procedure and later at 14 days follow-up
      (baseline value 63.4 +/- 31.3 MUL per cardiac cycle vs 32.0 +/- 28.4 MUL per
      cardiac cycle postprocedure [P = .0013] and 32.0 +/- 28.4 MUL per cardiac cycle
      at 14 days [P = .0015]). Pathology showed signs of severe limb ischemia in all
      rabbits with subacute and chronic injury patterns. CONCLUSIONS: A rabbit hind
      limb ischemia model created by percutaneous transauricular distal femoral artery
      embolization with calibrated particles may overcome some of the limitations of
      existing animal models. As such, this model could prove useful for assessing
      therapies designed to improve arterial perfusion and collateral growth.

PMID- 29074109
TI  - Racial disparities in outcomes after intact abdominal aortic aneurysm repair.
AB  - OBJECTIVE: We aimed to compare perioperative morbidity and mortality and late
      survival among black, white, and Asian patients undergoing intact abdominal
      aortic aneurysm (AAA) repair. METHODS: We identified all patients undergoing
      intact, infrarenal AAA repair in the Vascular Quality Initiative (VQI) from 2003
      to 2017. We compared in-hospital outcomes by race using the Fisher exact and
      Kruskal-Wallis tests. Multivariable logistic and linear regression models of
      perioperative outcomes adjusted for differences in demographics, comorbidities,
      hospital volume, and procedure. We used Cox regression to evaluate late survival
      by race. RESULTS: In the cohort, 21,961 (94%) patients were white, 1215 (5.2%)
      were black, and 318 (1.4%) were Asian. Black patients were more likely to be
      symptomatic (black, 16%; white, 9.1%; Asian, 11%; P < .001) and to undergo
      endovascular aneurysm repair (EVAR; black, 87%; white, 83%; Asian, 84%; P <
      .001). There were no differences in 30-day mortality after EVAR (black, 1.1%;
      white, 1.1%; Asian, 0.8%; P = .80) or open repair (black; 4.3%; white, 2.6%;
      Asian, 1.9%; P = .33). However, black patients were more likely to receive new
      postoperative dialysis (black, 1.6%; white, 0.8%; Asian; 0.7%; P = .01) and to
      return to the operating room (black, 4.3%; white, 2.9%; Asian, 0.9%; P < .01).
      Mean hospital length of stay was longer in black patients after EVAR (black, 3.3
      days; white, 2.6 days; Asian, 2.6 days; P < .001) and in Asian and black patients
      after open repair (black, 10.5 days; white, 8.5 days; Asian, 13.0 days; P <
      .001). After multivariable adjustment, black patients were more likely than white
      patients to have postoperative dialysis (odds ratio, 2.2; 95% confidence interval
      [CI], 1.3-3.6; P < .01) and return to the operating room (odds ratio, 1.6; 95%
      CI, 1.2-2.2; P < .01). Five-year survival was highest for Asian patients (black,
      84%; white, 85%; Asian, 92%), even in the adjusted Cox model (Asian: hazard
      ratio, 0.6; 95% CI, 0.4-0.97; P = .04). CONCLUSIONS: Although perioperative
      mortality is comparable across races after AAA repair, black patients are more
      likely than white or Asian patients to develop new postoperative renal failure
      and return to the operating room, even after adjusting for differences in
      comorbidities, operative variables, and hospital volume. In addition, whereas
      Asian patients have the highest rate of postoperative myocardial infarction, they
      also have the highest late survival. Further studies are warranted to elucidate
      the mechanism of these disparities.

PMID- 29074111
TI  - Polar orientation of renal grafts within the proximal seal zone affects risk of
      early type IA endoleaks after chimney endovascular aneurysm repair.
AB  - OBJECTIVE: The objective of this study was to describe the polar orientation of
      renal chimney grafts within the proximal seal zone and to determine whether graft
      orientation is associated with early type IA endoleak or renal graft compression
      after chimney endovascular aneurysm repair (ch-EVAR). METHODS: Patients who
      underwent ch-EVAR with at least one renal chimney graft from 2009 to 2015 were
      included in this analysis. Centerline three-dimensional reconstructions were used
      to analyze postoperative computed tomography scans. The 12-o'clock polar position
      was set at the takeoff of the superior mesenteric artery. Relative polar
      positions of chimney grafts were recorded at the level of the renal artery
      ostium, at the mid-seal zone, and at the proximal edge of the graft fabric. Early
      type IA endoleaks were defined as evidence of a perigraft flow channel within the
      proximal seal zone. RESULTS: There were 62 consecutive patients who underwent ch
      EVAR (35 double renal, 27 single renal) for juxtarenal abdominal aortic aneurysms
      with a mean follow-up of 31.2 months; 18 (29%) early type IA "gutter" endoleaks
      were identified. During follow-up, the majority of these (n = 13; 72%) resolved
      without intervention, whereas two patients required reintervention (3.3%).
      Estimated renal graft patency was 88.9% at 60 months. Left renal chimney grafts
      were most commonly at the 3-o'clock position (51.1%) at the ostium, traversing
      posteriorly to the 5- to 7-o'clock positions (55.5%) at the fabric edge. Right
      renal chimney grafts started most commonly at the 9-o'clock position (n = 17;
      33.3%) and tended to traverse both anteriorly (11 to 1 o'clock; 39.2%) and
      posteriorly (5 to 7 o'clock; 29.4%) at the fabric edge. In the polar plane, the
      majority of renal chimney grafts (n = 83; 85.6%) traversed <90 degrees before
      reaching the proximal fabric edge. Grafts that traversed >90 degrees were
      independently associated with early type IA endoleaks (odds ratio, 11.5; 95%
      confidence interval, 2.1-64.8) even after controlling for other device and
      anatomic variables. Polar orientation of the chimney grafts was not associated
      with graft kinking or compression (P = .38) or occlusion (P = .10). Takeoff angle
      of the renal arteries was the most significant predictor of chimney graft
      orientation. Caudally directed arteries (takeoff angle >30 degrees) were less
      likely to have implanted chimney grafts that traversed >90 degrees in polar angle
      (odds ratio, 0.09; 95% confidence interval, 0.01-0.55). CONCLUSIONS: Renal
      chimney grafts vary considerably in both starting position and their polar
      trajectory within the proximal seal zone. Grafts that traverse >90 degrees in
      polar angle within the seal zone may be at increased risk of early type IA
      endoleaks and require more frequent imaging surveillance. Caudally directed renal
      arteries result in a more favorable polar geometry (eg, cranial-caudal
      orientation) with respect to endoleak risk and thus are more ideal candidates for
      parallel graft strategies.

PMID- 29074112
TI  - Identifying content gaps in health status measures for intermittent claudication
      using the International Classification of Functioning, Disability and Health.
AB  - OBJECTIVE: The Walking Impairment Questionnaire (WIQ) and Intermittent
      Claudication Questionnaire (ICQ) are commonly used patient-reported functional
      outcome measures for intermittent claudication, but their functional
      representation has not been characterized. The World Health Organization's
      International Classification of Functioning, Disability and Health (ICF)
      framework comprehensively describes health-related function and has been used to
      evaluate health status and quality of life (QOL) measures. We applied a content
      analysis technique commonly used in functional rehabilitation research to
      evaluate ICF domains represented by WIQ and ICQ to characterize their health
      status and functional representation. METHODS: The overall perspective of each
      question was assigned as health status-function, health status-disability,
      Environment-facilitator, Environment-barrier, or QOL. All meaningful concepts in
      each question were identified and linked to the most appropriate and precise ICF
      code from the hierarchy of component, chapter, or category using the validated
      technique. A 20% random sample of questions was secondarily coded with
      disagreements resolved by discussion. RESULTS: Codability was agreed upon for 87%
      of questions; agreement was 100% on component and chapter and 88% on category.
      WIQ contains 18 concepts among 14 questions (1.3 concepts per question); all
      questions are from the health status-disability perspective. All WIQ concepts are
      from the "Activities/Participation-d" ICF component, "Mobility-d4" chapter.
      "Walking long distances" (d4501, >1 km) is omitted. ICQ contains 37 codable
      concepts among 16 questions (2.3 concepts per question). Thirteen questions are
      from health status-disability perspective, three from QOL. Sox of the nine
      chapters of the "Activities/Participation-d" ICF component are represented by 20
      of 37 concepts; 11 of 20 in the "Mobility-d4" chapter. The other
      "Activities/Participation-d" chapters and categories in ICQ are
      "Learning/applying knowledge" ("thinking-d163"), "General tasks/demands"
      ("carrying out daily routine-d230"), "Domestic life" ("shopping-d6200," "doing
      housework-d640"), "Major life areas" ("Maintaining a job-d8451"), and "Community
      life" ("socializing-d9205," "hobbies-d9204"). "Body Functions-b" ICF component is
      represented 11 times, covering pain, numbness, emotion, mood, and cardiovascular
      functions. "Body Structures-s" is represented three times as lower extremity.
      Neither WIQ nor ICQ specifically addresses "Walking on different surfaces,"
      (64,502) "Walking around obstacles" (d4503), or "Moving around using equipment"
      (d465), which includes assistive devices. Walking on an incline is not addressed
      in WIQ, ICQ, or the ICF. CONCLUSIONS: Applying this ICF-based content assessment
      methodology to patient-reported vascular disease outcome measures is feasible,
      representing a novel method of assessing such instruments. WIQ's scope is
      limited; it does not address functional capacity and covers only health status
      pertaining to walking disability. The ICQ is more inclusive, but concept density
      may obscure meaning. Neither instrument is functionally comprehensive and both
      have significant omissions that should be considered for inclusion.

PMID- 29074113
TI  - Prospective cohort 20 years after endovascular treatment for abdominal aortic
      aneurysm.
AB  - OBJECTIVE: To describe the factors associated with survival 20 years after
      endovascular treatment of an abdominal aortic aneurysm (AAA) in a single center.
      METHODS: Prospective cohort of asymptomatic patients with an infrarenal aortic
      aneurysm treated with a bifurcated endovascular graft (Talent) between June 1997
      and August 2008. Cox proportional hazard multivariable regression was used for
      analysis of independent risk factors for survival. Kaplan-Meier curves were done
      with the long-rank test. P < .05 was considered significant. RESULTS: We followed
      229 patients, 184 without an endoleak and 45 with an endoleak. Ages ranged
      between 52 and 89 years, and the mean diameter of the aneurysm was 59.51 +/- 14.6
      mm. Implantation of the endovascular graft was possible in 99% of the patients.
      The 30-day mortality rate was 3.4%. In the Cox regression, age <73 years (hazard
      ratio [HR], 0.42; 95% confidence interval [CI], 0.27-0.64), aneurysm size <=55 mm
      (HR, 0.62; 95% CI, 0.40-0.95), male sex (HR, 0.17; 95% CI, 0.05-0.52), American
      Society of Anesthesiologists surgical risk category I and II vs III and IV (HR,
      0.51; 95% CI, 0.34-0.75), and aneurysm size reduction <=3 mm after treatment (HR,
      2.23; 95% CI, 1.11-4.51) were significantly correlated with the survival of the
      patients followed in this long-term case series. CONCLUSIONS: This 20-year
      prospective cohort included patients with an AAA treated with a bifurcated
      endovascular graft (Talent) at a university hospital in Brazil. This study
      supports that sex, age, aneurysm size, aneurysm size reduction, and American
      Society of Anesthesiologists surgical risk category are significantly correlated
      with patient survival after endovascular treatment of the AAA.

PMID- 29074114
TI  - Regional variation in the cost of infrainguinal lower extremity bypass surgery in
      the United States.
AB  - BACKGROUND: Lower extremity bypass (LEB) remains the gold standard
      revascularization procedure in patients with peripheral arterial disease. The
      cost of LEB substantially varies based on patient's characteristics and
      comorbidities. The aim of this study was to assess regional variation in
      infrainguinal LEB cost and to identify the specific health care expenditures per
      service that are associated with the highest cost in each region. METHODS: We
      identified adult patients who underwent infrainguinal LEB in the Premier database
      between June 2009 and March 2015. Generalized linear regression models were used
      to report differences between regions in total in-hospital cost and service
      specific cost adjusting for patient's demographics, clinical characteristics, and
      hospital factors. RESULTS: A total of 50,131 patients were identified. The median
      in-hospital cost was $13,259 (interquartile range, $9308-$19,590). The cost of
      LEB was significantly higher in West and Northeast regions with a median cost of
      nearly $16,000. The high cost in the Northeast region was driven by the fixed
      (indirect) cost, whereas the driver of the high cost in the West region was the
      variable (direct) cost. The adjusted total in-hospital cost was significantly
      higher in all regions compared with the South (mean difference, West, $3752 [95%
      confidence interval (CI), 3477-4027]; Northeast, $2959 [95% CI, 2703-3216];
      Midwest, 1586 [95% CI, 1364-1808]). CONCLUSIONS: In this study, we show the
      marked regional variability in LEB costs. This disparity was independent from
      patient clinical condition and hospital factors. Cost inequality across the US
      represents a financial burden on both the patient and the health system.

PMID- 29074116
TI  - Discussion.

PMID- 29074115
TI  - Characterization and outcomes of reinterventions in Food and Drug Administration
      approved versus trial endovascular aneurysm repair devices.
AB  - OBJECTIVE: Published rates of reintervention after endovascular aneurysm repair
      (EVAR) range from 10% to 30%. We evaluated a single university center's
      experience with reinterventions in the context of Food and Drug Administration
      (FDA)-approved and trial devices. METHODS: Retrospective data collection was
      performed for patients who underwent infrarenal EVAR and required reintervention
      from 2000 to 2016. Trial devices included those used in FDA feasibility and
      pivotal trials. Time-to-event analysis was performed using Cox regression.
      Predictors of mortality and explantation were evaluated using logistic
      regression; survival analysis was performed using Kaplan-Meier methods. RESULTS:
      From 2000 to 2016, there were 1835 EVARs performed, and 137 patients (116 men;
      mean age, 72.2 +/- 10.0 years) underwent reintervention with a mean aneurysm size
      of 5.9 +/- 1.2 cm. The median follow-up was 5 years with an overall survival of
      70.1%. The overall reintervention rate was 7.5%. FDA-approved devices had a
      reintervention rate of 6.4%, whereas trial devices had a rate of 14.4% (P <
      .001). For all devices, the most common cause of reintervention was type II
      endoleak (52.5%), followed by type I endoleak (18.2%), type III endoleak (9.5%),
      limb kink (7.3%), iliac occlusive disease (5.8%), endotension (1.5%), and other.
      The overall mean time to first reintervention was 2.3 +/- 2.5 years, and
      univariate Cox regression identified male gender (hazard ratio, 1.91; 95%
      confidence interval [CI], 1.17-3.10; P = .010) and age at the time of EVAR
      (hazard ratio, 1.03; 95% CI, 1.01-1.05; P = .006) as risk factors for time to
      first reintervention. Among patients requiring reintervention, the mean number of
      reinterventions for trial devices was significantly greater than that for FDA
      approved devices (2.18 vs 1.65; P = .01). Trial devices requiring reintervention
      had a nearly threefold higher odds for the need for more than two reinterventions
      (odds ratio, 2.88; 95% CI, 1.12-7.37; P = .034). Trial device, cause of
      reintervention, and type of reintervention were not predictive of the need for
      explantation or mortality, but the number of reinterventions was significantly
      associated with the need for explantation (odds ratio, 1.86; 95% CI, 1.17-2.96; P
      = .012). EVAR device and the need for explantation did not have an impact on
      mortality. CONCLUSIONS: Despite the rigorous nature of patient enrollment in
      clinical trials and the development of newer iterations of investigational
      devices, patients undergoing EVAR with trial devices are more likely to undergo a
      greater number of reinterventions than with FDA-approved devices. Although
      mortality and the need for explantation were not significantly associated with
      trial devices, the finding of a greater number of reinterventions highlights the
      need to properly inform patients willing to partake in investigational device
      trials.

PMID- 29074119
TI  - Thoracic superior duct cyst: An incidental finding.

PMID- 29074117
TI  - Intensive care unit admission after endovascular aortic aneurysm repair is
      primarily determined by hospital factors, adds significant cost, and is often
      unnecessary.
AB  - BACKGROUND: A large proportion of endovascular aortic aneurysm repair (EVAR)
      patients are routinely admitted to the intensive care unit (ICU) for
      postoperative observation. In this study, we aimed to describe the factors
      associated with ICU admission after EVAR and to compare the outcomes and costs
      associated with ICU vs non-ICU observation. METHODS: All patients undergoing
      elective infrarenal EVAR in the Premier database (2009-2015) were included.
      Patients were stratified as ICU vs non-ICU admission according to location on
      postoperative day 0. Both patient-level (sociodemographics, comorbidities) and
      hospital-level (teaching status, hospital size, geographic location) factors were
      analyzed using univariate and multivariable logistic regression to determine
      factors associated with ICU vs non-ICU admission. Overall outcomes and hospital
      costs were compared between groups. RESULTS: Overall, 8359 patients underwent
      elective EVAR during the study period, including 4791 (57.3%) ICU and 3568
      (42.7%) non-ICU admissions. Patients admitted to ICU were more frequently
      nonwhite and had more comorbidities, including congestive heart failure, coronary
      artery disease, chronic kidney disease, chronic obstructive pulmonary disease,
      diabetes, and hypertension, than non-ICU patients (all, P < .03). ICU admissions
      were more common in small (<300 beds), urban, and nonteaching hospitals and
      varied greatly depending on surgeon specialty and geographic region (P < .001). A
      pattern emerged when admission location was clustered by hospital; ICU patients
      were treated at hospitals where 96.7% (interquartile range, 84.5%-98.9%) of
      patients were admitted to ICU after EVAR, whereas non-ICU patients were treated
      at hospitals where only 7.5% (interquartile range, 4.9%-25.8%) were admitted to
      ICU after EVAR. A multivariable logistic regression model accounting for patient
      , operative-, and hospital-level differences had a significantly lower area under
      the curve for predicting ICU admission after EVAR than a model accounting only
      for hospital factors (area under the curve, 0.76 vs 0.95; P < .001). The overall
      rate of adverse events was higher for ICU vs non-ICU patients (16.3% vs 13.7%; P
      < .001). Failure to rescue (2.9% vs 3.9%; P = .42) and in-hospital mortality
      (0.4% vs 0.4%; P = .81) were similar between groups. After adjusting for patient
      and hospital factors as well as for postoperative adverse events, ICU admission
      after EVAR cost $1475 (95% confidence interval, $768-2183) more than non-ICU
      admission (P < .001). CONCLUSIONS: Among patients undergoing elective EVAR,
      postoperative ICU admission is more closely associated with hospital practice
      patterns than with individual patient risk. Routine ICU admission after EVAR adds
      significant cost without reducing failure to rescue or in-hospital mortality.

PMID- 29074118
TI  - An update on the incidence of perioperative outcomes after carotid
      endarterectomy, stratified by type of preprocedural neurologic symptom.
AB  - OBJECTIVE: Perioperative complications after carotid endarterectomy (CEA) have
      decreased over time. Therefore, we aimed to provide an update on 30-day outcomes
      after CEA, stratified by type of preprocedural neurologic symptom. METHODS: We
      included all CEAs from the Targeted Vascular module of the American College of
      Surgeons National Surgical Quality Improvement Program (ACS-NSQIP, 2011-2015) and
      stratified patients based on type of preprocedural neurologic symptom, that is,
      asymptomatic, ocular transient ischemic attack (TIA), hemispheric TIA, and
      stroke. We compared 30-day outcomes across the groups, with 30-day stroke/death
      as our primary endpoint. RESULTS: Of 16,739 CEA patients, 9784 were asymptomatic
      (58%). Among the 6955 symptomatic patients, 1216 (17%) had a preprocedural ocular
      TIA, 2635 (38%) a preprocedural hemispheric TIA, and 3104 (45%) a preprocedural
      stroke. Preprocedural stroke patients had higher 30-day stroke/death rates
      compared with those with a preprocedural hemispheric TIA, or ocular TIA, or
      asymptomatic patients (5.0% vs 3.3%, 1.9%, and 1.8%, respectively; all P < .001),
      primarily owing to differences in perioperative 30-day stroke rates, with 4.1% vs
      2.5%, 1.4%, and 1.3%, respectively (all P < .001). CONCLUSIONS: Among symptomatic
      CEA patients, those with a preprocedural stroke had a high perioperative 30-day
      stroke/death rate, compared with those patients with either a preprocedural
      hemispheric or ocular TIA. Therefore, the common stratification applied to CEA
      patients, which groups all symptomatic patients, should be avoided, especially as
      the relative proportion of symptomatic patients with a preprocedural stroke vs
      those with a hemispheric or ocular TIA will affect the overall outcome for all
      symptomatic patients after CEA.

PMID- 29074120
TI  - Incretin-based therapy in type 2 diabetes: An evidence based systematic review
      and meta-analysis.
AB  - Incretin based therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and
      glucagon-like peptide-1 receptor agonists (GLP-1Ra) are increasingly used for the
      treatment of Type 2 diabetes mellitus. In clinical practice and in previously
      performed clinical trials, these agents are often used in combination with other
      oral anti-diabetic agents (OADs) and Insulin. Prior meta-analytic reviews however
      do not adequately address the impact of background therapy and active comparator
      arms. Accordingly, we aimed to further investigate the efficacy of incretin based
      therapies by updating existing reviews by including clinical trial evidence after
      2008; estimating the pooled effect of incretin therapies on glycemic efficacy and
      weight-loss, stratified by comparator therapy (placebo, mono-therapy, etc.),
      estimating the impact of background OADs and within class (GLP-1Ra or DPP-4i)
      comparative efficacy, on glycemia control. 82 randomized controlled trials after
      2008 with glycemic control and weight loss as primary end-points were included.
      Both DPP-4i and GLP-1Ra reduced HbA1c, but only GLP-1Ra caused weight loss when
      compared to either active comparator drugs or placebo. GLP-1Ra were more
      effective than DPP-4i in glycemia lowering. Long acting GLP-1Ra were more
      effective in HbA1c lowering than short-acting agents but with similar weight loss
      effect. The effect of DPP-4i incretin glycemic efficacy was not modified by
      background therapy used in the study.

PMID- 29074121
TI  - Baseline level and change in serum albumin concentration and the risk of incident
      type 2 diabetes.
AB  - AIMS: We aimed to determine whether baseline level and change in serum albumin
      concentration are predictive of future development of type 2 diabetes (T2D).
      METHODS: A total of 15,428 subjects (8764 men and 6664 women) without diabetes at
      baseline, aged 21-88years (mean age of 51.0years), were enrolled from a health
      screening program. RESULTS: During the 5-year follow-up period, a total of 599
      incident cases (3.9%) of T2D developed. Higher baseline serum albumin
      concentration was associated with increased T2D risk, independent of age, sex, or
      body mass index; however, this association was confounded and was not significant
      after further adjustment for other T2D risk factors. Compared with subjects in
      the lowest tertile of change in serum albumin concentration, subjects in the
      highest tertile showed a lower risk for T2D development, independent of risk
      factors for T2D and baseline serum albumin concentration [OR (95% CI), 0.30 (0.21
      0.43), p for trend <0.001]. CONCLUSION: Higher baseline serum albumin
      concentration was not an independent risk factor of future T2D, whereas an
      increase in serum albumin concentration was independently associated with a lower
      diabetes risk.

PMID- 29074122
TI  - Erratum to Dan Ziegler, Sally Edmundson, Irina Gurieva, Boris Mankovsky, Nikolaos
      Papanas, Igor Strokov. Predictors of response to treatment with actovegin for 6
      months in patients with type 2 diabetes and symptomatic polyneuropathy. J
      Diabetes Complications 2017; 31:1181-7.

PMID- 29074123
TI  - Type 2 diabetes, depressive symptoms and disability over a 15-year follow-up
      period in older Mexican Americans living in the southwestern United States.
AB  - AIMS: To evaluate how depression and diabetes severity impact disability
      progression among Mexican Americans over a 15-year period. METHODS: We used seven
      waves of the Hispanic Established Population for the Epidemiologic Study of the
      Elderly (H-EPESE). Primary disability outcomes included the Activities of Daily
      Living (ADL) and Instrumental Activities of Daily Living (IADL) scales.
      Explanatory variables included time since diagnosis with diabetes (no type 2
      diabetes, 1-10, 11-20, 21+), an indicator of disease severity, and depression.
      Longitudinal generalized estimating equation models were used to estimate the
      relationship between time since diabetes diagnosis, depressive symptoms and ADL
      and IADL disability progression over a 15-year time period. RESULTS: Years since
      diabetes diagnosis was associated with more rapid ADL and IADL disability
      progression compared to those without type 2 diabetes. Depression accelerated the
      disabling process in participants who were diagnosed with diabetes 11years or
      more years ago. CONCLUSIONS: Longer duration of diabetes and greater symptoms of
      depression increase vulnerability for disability among older Mexican American
      adults.

PMID- 29074124
TI  - Revision rhinoplasty: physician-patient aesthetic and functional evaluation.
AB  - INTRODUCTION: Approximately 5-15% of patients submitted to rhinoplasty operations
      undergo revision surgery. Those patients have varied functional and aesthetic
      complaints that should receive a detailed assessment that includes all the
      expectations the patient had before the previous procedure. OBJECTIVE: To draw
      the profile of the main aesthetic-functional complaints reported by patients to
      be submitted to revision rhinoplasty and to correlate them with the internal and
      external objective nasal evaluation performed by the surgeon. METHODS: A
      prospective study was conducted with 43 patients to be submitted to revision
      rhinoplasty and their respective surgeons, by applying a questionnaire about the
      patients' epidemiological questions and subjective aesthetic-functional
      complaints as well as the respective functional deformities observed by the
      surgeons. Subsequently, these data were correlated with the purpose of observing
      the frequency of congruent reports between physicians and patients. RESULTS: The
      presence of drooping tip and residual bridge hump were the patients' main
      complaints, confirmed by the surgeons. The correlation between subjective
      obstructive symptoms and the intranasal evaluation performed by surgeons was
      shown to be present in 87.5% of the cases. Among the patients with respiratory
      symptoms, the main deformity identified was residual septal deviation in 56.25%
      of the cases. CONCLUSION: The drooping tip followed by residual hump were the
      main complaints reported by the patients and confirmed by the objective
      examination by the physicians. The presence of nasal obstructive complaints in
      37.2% of the patients shows that greater attention needs to be paid to functional
      deformities during the first surgical procedure. The differences observed between
      patients' complaints and surgeons' evaluations confirm the need for detailed
      assessment and clarification to the patients regarding their expectations and
      actual surgical possibilities.

PMID- 29074125
TI  - Status epilepticus triggers long-lasting activation of complement C1q-C3
      signaling in the hippocampus that correlates with seizure frequency in
      experimental epilepsy.
AB  - Status epilepticus (SE) triggers a myriad of neurological alterations that
      include unprovoked seizures, temporal lobe epilepsy (TLE), and cognitive
      deficits. Although SE-induced loss of hippocampal dendritic structures and
      synaptic remodeling are often associated with this pathophysiology, the
      underlying mechanisms remain elusive. Recent evidence points to the classical
      complement pathway as a potential mechanism. Signaling through the complement
      protein C1q to C3, which is cleaved into smaller biologically active fragments
      including C3b and iC3b, contributes to the elimination of synaptic structures in
      the normal developing brain and in models of neurodegenerative disorders. We
      recently found increased protein levels of C1q and iC3b fragments in human drug
      resistant epilepsy. Thus, to identify a potential role for C1q-C3 in SE-induced
      epilepsy, we performed a temporal analysis of C1q protein levels and C3 cleavage
      in the hippocampus along with their association to seizures and hippocampal
      dependent cognitive functions in a rat model of SE and acquired TLE. We found
      significant increases in the levels of C1q, C3, and iC3b in the hippocampus at 2
      , 3- and 5-weeks after SE relative to controls (p<0.05). In the SE group, greater
      iC3b levels were significantly correlated with higher seizure frequency (p<0.05).
      Together, these data support that hyperactivation of the classical complement
      pathway after SE parallels the progression of epilepsy. Future studies will
      determine whether C1q-C3 signaling contributes to epileptogenic synaptic
      remodeling in the hippocampus.

PMID- 29074126
TI  - Fasting plasma glucose and variation in cardiometabolic risk factors in people
      with high-risk HbA1c-defined prediabetes: A cross-sectional multiethnic study.
AB  - AIMS: Variation in cardiometabolic risk in prediabetes and any impacts of
      ethnicity on such variation have been little studied. In an ethnically diverse
      dataset, selected according to a high-risk HbA1c-based definition of prediabetes,
      we have investigated relationships between glycaemia and cardiometabolic risk
      factors and the influence of ethnicity on these relationships. METHODS: We
      undertook a cross-sectional analysis of baseline data from a diabetes prevention
      study in the UK and a chronic care clinic in Thailand, selected for people
      without diabetes (fasting plasma glucose <7.0 mmol/l) with HbA1c 6.0-6.4% (42-47
      mmol/mol). Thai (n=158) and UK White (n=600), South Asian (n=112), Black (n=70)
      and other/mixed (n=103) groups were distinguished and measurements included
      fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance
      related risk factors (IRFs). RESULTS: Independently of individual characteristics
      including ethnicity, only systolic BP was weakly associated with FPG (beta
      coefficient 1.76 (95%CI 0.10-3.42), p 0.03) and only LDL-c with IFG (FPG 5.6 to
      <7) (adjusted -0.14 (-0.27, -0.003) p 0.04). There were no significant
      independent associations with cardiometabolic risk factors when categories of
      impaired fasting glucose (FPG >= 6.1 to <7.0 mmol/L) were considered. Relative to
      White, South Asian ethnicity was independently associated with lower systolic and
      diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having
      2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non
      white ethnicities with lower total and LDL cholesterol. CONCLUSION: In high-risk
      HbA1c-defined prediabetes additional measurement of FPG will add little to
      evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most
      adverse cardiometabolic profile of any ethnic group.

PMID- 29074127
TI  - Sex differences in the pituitary TGFbeta1 system: The role of TGFbeta1 in
      prolactinoma development.
AB  - Prolactinomas are the most frequent functioning pituitary adenomas, and sex
      differences in tumor size, behavior and incidence have been described. These
      differences have been associated with earlier diagnosis in woman, as well as with
      serum estradiol levels. Experimental models of prolactinomas in rodents also show
      a higher incidence in females, and recent findings suggest that gender
      differences in the transforming growth factor beta 1 (TGFbeta1) system might be
      involved in the sex-specific development of prolactinomas in these models. The
      aim of this review is to summarize the literature supporting the important role
      of TGFbeta1 as a local modulator of pituitary lactotroph function and to provide
      recent evidence for TGFbeta1 involvement in the sex differences found in
      prolactinoma development in animal models.

PMID- 29074128
TI  - A Randomized Controlled Study of the Use of Video Double-Lumen Endobronchial
      Tubes Versus Double-Lumen Endobronchial Tubes in Thoracic Surgery.
AB  - OBJECTIVE: To compare the incidence of fiberoptic bronchoscope (FOB) use (1)
      during verification of initial placement and (2) for reconfirmation of correct
      placement following repositioning, when either a double-lumen tube (DLT) or video
      double-lumen tube (VDLT) was used for lung isolation during thoracic surgery.
      DESIGN: A randomized controlled study. SETTING: Single-center university teaching
      hospital. PARTICIPANTS: The study comprised 80 patients who were 18 years or
      older requiring lung isolation for surgery. INTERVENTIONS: After institutional
      review board approval, patients were randomized prior to surgery to either DLT or
      VDLT usage. Attending anesthesiologists placed the Mallinckrodt DLT or Vivasight
      (ET View Ltd, Misgav, Israel) VDLT with conventional laryngoscopy or video
      laryngoscopy then verified correct tube position through the view provided with
      either VDLT external monitor or FOB. MEASUREMENTS AND MAIN RESULTS: Data
      collected included: sex, body mass index, successful intubation and endobronchial
      placement, intubation time, confirmation time of tube position, FOB use, quality
      of view, dislodgement of tube, and ability to forewarn dislodgement of
      endobronchial cuff and complications. FOB use for verification of final position
      of the tube (VDLT 13.2% [5/38] v DLT 100% [42/42], p < 0.0001), need for FOB to
      correct the dislodgement (VDLT 7.7% [1/13] v DLT 100% [14/14], p < 0.0001),
      dislodgement during positioning (VDLT 61.5% [8/13] v DLT 64.3% [9/14], p = ns),
      dislodgement during surgery (VDLT 38.5% [5/13] v DLT 21.4% [3/14], p = ns), and
      ability to forewarn dislodgement of endobronchial cuff (VDLT 18.4% [7/38] v DLT
      4.8% [2/42], p = 0.078). CONCLUSION: This study demonstrated a reduction of 86.8%
      in FOB use, which was a similar reduction found in other published studies.

PMID- 29074129
TI  - Selected 2016 Highlights in Congenital Cardiac Anesthesia.

PMID- 29074131
TI  - Grouper MAVS functions as a crucial antiviral molecule against nervous necrosis
      virus infection.
AB  - Mitochondrial antiviral signaling protein (MAVS), also known as IPS-1, VISA, and
      Cardif, has been well studied for its crucial roles in the mammalian interferon
      immune response. To better understand the actions of MAVS in fish immune
      response, a MAVS homolog from orange spotted grouper (Epinephelus coioides)
      (EcMAVS) was cloned and characterized in this study. EcMAVS encoded a 563-amino
      acid peptide which showed 64% and 20% identity to rock bream (Oplegnathus
      fasciatus) and human (Homo sapiens), respectively. Sequence alignment analysis
      showed that EcMAVS shared a conserved CARD domain at N terminal, a central
      proline-rich region and a TM domain at C terminal. Phylogenetic analysis
      indicated that EcMAVS showed the nearest relationship to rock bream, followed by
      other fishes, birds and mammals. In healthy grouper, the transcript of EcMAVS was
      predominantly detected in gill, intestine and skin. In vitro, the expression
      level of EcMAVS was significantly increased during red-spotted grouper nervous
      necrosis virus (RGNNV) infection, but only slightly increased at the late stage
      of Singapore grouper iridovirus (SGIV) infection, suggested the EcMAVS might
      exert various roles in response to different viruses. Subcellular localization
      analysis showed that the fluorescence in EcMAVS transfected cells primarily co
      localized with mitochondria. Overexpression of EcMAVS in grouper cells
      significantly inhibited the replication of RGNNV, demonstrated by the delay of
      CPE progression and the decrease of viral gene transcription. Differently, the
      replication of SGIV was almost not affected by the ectopic expression of EcMAVS.
      Furthermore, our results also showed that EcMAVS overexpression significantly
      increased the expression of interferon related cytokines, and activated both IRF3
      and IRF7-mediated interferon promoter activities. Taken together, our results
      demonstrated that grouper MAVS exerted antiviral function against nodavirus
      infection via up-regulating the interferon immune response.

PMID- 29074130
TI  - Heat-induced oxidative stress and inflammation involve in cadmium pollution
      history in the spleen of zebrafish.
AB  - Zebrafish were exposed to 0, 2.5 and 5 MUg/L cadmium (Cd) for 10 weeks, and then
      each group was exposed to 26  degrees C(control) and 32  degrees C (high
      temperature) for 7 days. 22 indicators were compared between 26  degrees C and 32
      degrees C in the spleen, including body weight, LPO and NO levels, activity
      levels of Cu/Zn-SOD, CAT and iNOS, MTs protein levels, and mRNA levels of Nrf2,
      Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1, MTs, IL-6, IL-10, IL-1beta, TNF-alpha,
      iNOS and NF-kappaB. Most indicators were not significantly affected by heat in
      fish from no Cd pollution. However, almost all of indicators were responsive to
      heat in fish pre-exposed to Cd. Several indicators were sensitive to heat in fish
      pre-exposed to 2.5 MUg/L Cd such as iNOS activities, and mRNA levels of iNOS and
      IL-10. Most other indicators were sensitive to heat in fish pre-exposed to 5
      MUg/L. The mRNA levels of HSP70 and MTF-1 were up-regulated by heat in fish pre
      exposed to 0, 2.5 and 5 MUg/L Cd. However, the magnitude of increase was the
      greatest in fish pre-exposed to 5 MUg/L Cd. These differences between control and
      high temperature would serve as biomarkers to distinguish healthy from Cd
      polluted group. The findings imply that metal pollution history should be
      carefully considered when screening heat biomarkers in fish.

PMID- 29074132
TI  - MicroRNA-146a promotes red spotted grouper nervous necrosis virus (RGNNV)
      replication by targeting TRAF6 in orange spotted grouper, Epinephelus coioides.
AB  - MicroRNA-146a (miR-146a) has been demonstrated to function as a negative
      regulator of cellular immune responses against pathogens in mammals, however,
      little information focused on its functions in lower vertebrates. In this study,
      we investigated the regulatory roles of orange spotted grouper, Epinephelus
      coioides miR-146a during red spotted grouper nervous necrosis virus (RGNNV)
      infection. During RGNNV infection in grouper spleen (GS) cells, the endogenous
      expression level of miR-146a and tumor necrosis factor receptor-associated factor
      6 (TRAF6) significantly increased along with the infection time. Overexpression
      of miR-146a significantly facilitated viral infection, evidenced by the increased
      transcription of viral CP and RdRp genes, while miR-146a knockdown by specific
      inhibitors decreased RGNNV replication. Using pMIR-REPORT Luciferase system, we
      found that the 3' untranslated region (UTR) of grouper TRAF6 could be
      specifically targeted by miR-146a. Further studies showed that its downstream
      target gene pro-inflammatory cytokines, including TNF-alpha, IL-8 and IL-1beta,
      were all significantly decreased in miR-146a mimic transfected cells, but
      increased in miR-146a inhibitors transfected cells during RGNNV infection. Thus,
      our results suggested and verified that holding the level of miR-146a exerted
      crucial roles in RGNNV infection through TRAF6-mediated inflammatory response.

PMID- 29074133
TI  - Conservation of structural and interactional features of CD28 and CD80/86
      molecules from Nile tilapia (Oreochromis niloticus).
AB  - Interaction of CD28 with CD80 or CD86 molecules provides a costimulatory signals
      required in T cell activation. In this study, we cloned and analyzed a CD28 gene
      (On-CD28) and a CD80/86 gene (On-CD80/86) from Nile tilapia (Oreochromis
      niloticus). Sequence analysis revealed the typical characteristics of On-CD28
      protein; for instance, the proline-based motif (117TYPPPL122) is essential in
      binding of CD28 to CD80/86 ligands. Moreover, an extracellular Ig domain was
      found in On-CD80/86; this domain is responsible in binding of CD28 to CD80/86
      receptors. Subcellular localization analysis showed that both On-CD28 and On
      CD80/86 were distributed predominantly in the cytomembrane. Yeast two-hybrid
      assay showed that On-CD28 directly interacted with On-CD80/86. On-CD28 and On
      CD80/86 transcripts were detected in all the examined tissues of healthy Nile
      tilapia, and the highest expression levels of On-CD28 and On-CD80/86 were
      detected in the brain and heart, respectively. Following a bacterial challenge
      using Streptococcus agalactiae in vivo, On-CD28 and On-CD80/86 were upregulated
      in head kidney, spleen, intestines, and brain. However, they showed different
      expression profiles in response to stimulation with inactivated S. agalactiae in
      vitro. These findings indicated that the interaction of On-CD28 with On-CD80/86
      provides a costimulatory signals that possibly play an important role in T cell
      activation during S. agalactiae infection.

PMID- 29074134
TI  - Severe traumatic brain injuries in children: Does the type of trauma center
      matter?
AB  - BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death among
      injured children. Depending on geographic location, and trauma resources,
      pediatric patients may be treated at pediatric (PTC), adult (ATC), or mixed
      trauma centers (MTC). The effect of the type of trauma center on outcomes in
      severe TBI is not known. METHODS: NTDB study (2007-2014), level 1 trauma centers,
      patients <=14years with severe isolated TBI (head AIS>=3 and extracranial
      AIS<=2). Demographic, clinical and injury characteristics were abstracted.
      Logistic regression was used to compare outcomes between the three types of
      trauma centers. RESULTS: 10,402 patients met inclusion criteria. 4430 (42.6%)
      were admitted in PTC, 4044 (38.9%) in ATC and 1928 (18.5%) in MTC. Overall, 39.9%
      of patients had head AIS 3, 55.5% had AIS 4 and 4.6% AIS 5. Mortality was 3.2%
      (2.0% in PTC, 4.5% in ATC and 3.3% in MTC). On logistic regression, treatment at
      ATC was associated with significantly higher mortality than PTC (OR 1.55,
      p=0.011). There was no significant difference between PTC and MTC (p=0.394).
      There was no significant difference in mortality between the 3 types of trauma
      centers in the subgroups of patients with head AIS 3 or 5. However, patients with
      head AIS 4 treated at MTC had significantly lower mortality (OR 0.163, 95% CI
      0.053-0.501, p=0.002). CONCLUSION: Patients with isolated severe TBI treated at
      PTC have significantly better survival than patients treated at ATC, but not MTC.
      In the subgroup of patients with isolated TBI and a head AIS score of 4, patients
      treated at MTC have improved survival than those treated at PTC. LEVEL OF
      EVIDENCE: III.

PMID- 29074136
TI  - New Approach to Guide Target Prostate Biopsy: Technique and Initial Experience.
AB  - OBJECTIVE: To describe the technique of transrectal biopsy with a new device that
      fuses multiparametric magnetic resonance (mpMRI) and ultrasound images in real
      time to guide target biopsies and to evaluate our initial experience. METHODS:
      Patients with persistent suspicion of prostate cancer despite a previous negative
      biopsy and who had an mpMRI before the biopsy were selected. All patients
      underwent target biopsy plus standard systematic biopsy. Significant prostate
      cancer (sig PCa) was defined according to the Epstein criteria for standard
      biopsy and Gleason grade of >=7 and a positive core length of >=5 mm for target
      biopsy. RESULTS: The first 40 patients were evaluated. The median age was 65
      years old. In a sagittal isotropic sequence, the fusion process was started. The
      fusion can be improved by using different tools such as concordant points and
      Global Positioning System corrections tools. In the target biopsy, a median of 4
      cores was taken, whereas in the standard biopsy, 12 cores were taken. Twenty-two
      patients were diagnosed with prostate cancer; of these patients, 17 were
      diagnosed with sig PCa. The fusion target biopsy diagnosed more sig PCa than the
      standard biopsy; however, it was not statistically significant (37.5% vs 25%,
      P=.08). The probability of being diagnosed with cancer increased in correlation
      with the Prostate Imaging Reporting and Data System score, without reaching
      statistical significance (k=0.45, P=.08). CONCLUSIONS: This new device is a
      useful tool to guide biopsy in patients with target lesions in an mpMRI to
      increase the detection of sig PCa. A larger cohort would be required to show
      significant differences.

PMID- 29074137
TI  - Corrigendum to "Brain targeted PLGA nanocarriers alleviating amyloid-Beta
      expression and preserving basal survivin in degenerating mice model. Biochim
      Biophys Acta 2015, 1852(11):2423-31.

PMID- 29074135
TI  - Evaluation of effect of preoperative chemotherapy on Wilms' tumor histopathology.
AB  - PURPOSE: To evaluate usefulness of cutting needle biopsy (CNB) to recognize
      pediatric renal tumors and to predict the evolution of histology during
      preoperative chemotherapy of Wilms tumors. METHODS: Ninety pediatric patients
      were operated for renal tumors at our institution in 1988-2015. We included all
      64 patients who had undergone CNB at diagnosis and whose CNB and nephrectomy
      samples were available for re-evaluation. RESULTS: The CNB was diagnostic in all
      59 Wilms tumors but only in two out of five non-Wilms tumors. Anaplasia was
      missed by CNB in one of three with diffuse anaplasia in nephrectomy specimens. In
      Wilms tumors the proportions of the blastemal, stromal and epithelial components
      were 55% (IQR 25-85), 28% (IQR 10-58) and 2% (IQR 0-10) in CNB samples and 5%
      (IQR 0-64), 15% (IQR 0-50) and 15% (IQR 0-44) in the nephrectomy specimens (p
      values 0.002, 0.599 and 0.005 respectively). The degree of tumor necrosis was in
      median 80% (IQR 21-97), after preoperative chemotherapy. The degree of tumor
      necrosis after chemotherapy had a positive correlation with the proportion of
      blastemal component (p=0.008) and a negative correlation with proportion of
      epithelial component in pre-chemotherapy CNB samples (p<0.001). CONCLUSIONS:
      Wilms tumors are usually recognizable unlike non-Wilms tumors in CNB at
      diagnosis. In Wilms tumors, high blastemal cell content is associated with
      significant tumor necrosis during pre-operative chemotherapy. Our results do not
      support routine use of CNB in diagnosis of renal tumors. TYPE OF STUDY:
      Retrospective review. LEVEL OF EVIDENCE: Level III.

PMID- 29074138
TI  - Schistosoma mansoni: In vivo evaluation of Phyllanthus amarus hexanic and
      ethanolic extracts.
AB  - Human schistosomiasis is an important neglected tropical disease caused by blood
      flukes of the genus Schistosoma and is responsible for more than 280,000 deaths
      annually. Treatment for this disease relies currently on a single drug,
      praziquantel (PZQ). Concerns regarding PZQ resistance and insensitivity of
      juvenile schistosomes have increased the interest in resorting to medicinal
      plants for alternative drug therapies. This study aimed to perform an in vivo
      schistosomicidal activity evaluation of crude hexanic (HE) and ethanolic (EE)
      extracts obtained from Phyllanthus amarus in mice infected with Schistosoma
      mansoni (BH strain). Mice were treated orally with a single dose of 100 or 250
      mg/kg, on two different infection periods, 30 and 45 days post-infection (dpi).
      Parameters such as worm recovery, faecal egg count, intestinal tissue egg count
      and liver histopathology were evaluated. Treatment against young adult (30 dpi)
      and adult (45 dpi) worms were more effective compared to the control group
      treated with PZQ. At a concentration of 250 mg/kg (30 dpi) EE showed a 54.4%
      female reduction and a 61.2% total worm reduction whilst at a concentration of
      100 mg/kg (45 dpi) HE showed a 40.6% female worm reduction and a 45.3% total worm
      reduction. Histopathological examination showed a granuloma decrease in both
      number and size for groups treated with 250 mg/kg of HE (45 dpi) or EE (30 or 45
      dpi). From these results, it can be concluded that both hexanic and ethanolic
      extracts have antischistosomal activities, however, act differently according to
      the parasites age. The schistosomicidal activity results in groups treated 30
      days post infection is extremely important since praziquantel does not show
      activity against the juvenile forms of Schistosoma.

PMID- 29074140
TI  - Airborne Allergic Contact Dermatitis Caused by Neem Oil.

PMID- 29074139
TI  - Optogenetic control of focal adhesion kinase signaling.
AB  - Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor
      receptors and mechanical stress to control cell adhesion, motility, survival and
      proliferation. Here, we developed a single-component, photo-activatable FAK,
      termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2
      (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from
      physiological stimuli and activates downstream signaling rapidly and reversibly
      upon blue light exposure. OptoFAK stimulates SRC creating a positive feedback
      loop on FAK activation, facilitating phosphorylation of paxillin and p130Cas in
      adherent cells. In detached cells or in mechanically stressed adherent cells,
      optoFAK is autophosphorylated upon exposure to blue light, however, downstream
      signaling is hampered indicating that the accessibility to these substrates is
      disturbed. OptoFAK may prove to be a useful tool to study the biological function
      of FAK in growth factor and integrin signaling, tension-mediated focal adhesion
      maturation or anoikis and could additionally serve as test system for kinase
      inhibitors.

PMID- 29074141
TI  - Bullous Necrotic Purpura Caused by Scedosporium apiospermum Presenting With a
      Sporotrichoid Pattern.

PMID- 29074142
TI  - Blue Nevus With Satellite Lesions Mimicking Malignant Melanoma.

PMID- 29074143
TI  - RF-Immediate Lymph Node Dissection on Detection of Sentinel Lymph Node
      Involvement Does Not Increase Survival in Cutaneous Melanoma.

PMID- 29074144
TI  - Syringocystadenocarcinoma Papilliferum: Case Report and Review of the Literature.

PMID- 29074145
TI  - Treatment of Livedoid Vasculopathy With Rivaroxaban: A Potential Use of New Oral
      Anticoagulants for Dermatologists.

PMID- 29074146
TI  - Community pharmacists' beliefs regarding improvement of Star Ratings scores using
      the Theory of Planned Behavior.
AB  - OBJECTIVES: The Centers for Medicare and Medicaid Services (CMS) is moving toward
      a value-based model, which includes the Five-Star Quality Rating System (Star
      Ratings). Prescription Drug Plans include multiple pharmacy measures associated
      with adherence and patient safety that contribute to CMS Star Ratings scores.
      This study, using the Theory of Planned Behavior (TPB), explored factors
      associated with community pharmacists' beliefs to improve Star Ratings scores.
      DESIGN: Exploratory, qualitative, use of focus groups, and the TPB. SETTING AND
      PARTICIPANTS: Focus groups were performed in conference rooms at the College of
      Pharmacy main and satellite campuses. Participants were community retail
      pharmacists with an active Oklahoma license and 1 year of work experience. MAIN
      OUTCOME MEASURES: Each focus group was audio recorded and the recording
      transcribed to documents and analyzed with the use of a hybrid deductive and
      inductive qualitative approach rooted in a constant comparative framework. Coding
      of the data back to the TPB constitutes a deductive approach. The generation of
      themes and subthemes from other coded nodes constitutes an inductive approach.
      Analysts agreed on common themes, differences in findings, and saturation of the
      data gathered. RESULTS: Four focus groups were conducted with 26 participants in
      2 categories: pharmacists with and without experience improving Star Ratings.
      Pharmacists shared and contrasted in salient, normative, and control beliefs
      about patient outcomes, data, financial implications, staff, technology, and
      other stakeholders associated with performance of improving Star Ratings. Themes
      regarding medication adherence, patient safety, and intention were also found.
      CONCLUSION: The TPB was used to explore beliefs of community pharmacists about
      improving Star Ratings scores. Themes that were identified will assist in future
      research for measuring intention to improve CMS Star Ratings scores and the
      development of training and education programs.

PMID- 29074147
TI  - Cost savings impact of a pharmacist-initiated teleservice program for Medicare
      Part D reviews.
AB  - OBJECTIVES: To (a) determine potential cost savings of a pharmacy outreach
      teleservice program conducting Medicare Part D plan reviews for a large
      population of beneficiaries allowing for comparison of multiple preferences; and
      (b) explore client demographic comparisons, plan features, and stratification by
      cost and number of medications. METHODS: Retrospective cohort evaluation of a
      Medicare D review service during open enrollment period (October 15 to December
      7, 2012). Reviews were conducted at a university-based pharmacy outreach program
      in Massachusetts and completed by pharmacists (17%), case managers (52%), and
      students (31%). Recommendations were created by entering medication regimens into
      the Medicare.gov plan finder, and factors including deductible, premium, and
      copayment or coinsurance, formulary restrictions, secondary assistance, and
      annual cost were considered. A comparison of the overall cost of the client's
      2012 plan in 2013 with that of a lower-cost plan in the 2013 benefit year
      determined potential cost savings. RESULTS: Demographic data were available for
      1062 individuals, with the majority being women (66%), an overall mean age of 73
      years, and most living in a single household. Clients (75%) were taking 5 or more
      medications. Lower-cost plans were recommended for 61% of clients with a median
      cost savings valued at $538 per member, per year. Cost was the leading
      consideration for plan change (87.4%), followed by deductible (32.7%) and premium
      (30.1%). Cost savings were analyzed by evaluating current plan versus alternate
      plan by sex, age, client type (repeat vs. referred vs. new), and according to
      number of medications. Lower-cost plans were identified for 75% of new members.
      Individuals taking 0-14 medications had a cost savings of approximately $833 per
      client per year. CONCLUSION: Teleservice pharmacy outreach programs create value
      by identifying therapeutically comparable alternative plans and reducing plan
      spending while efficiently consulting for a large number of Medicare Part D
      beneficiaries statewide.

PMID- 29074148
TI  - Geometry and airflow dynamics analysis in the nasal cavity during inhalation.
AB  - BACKGROUND: A major issue among computational respiratory studies is the wide
      variety of nasal morphologies being studied, caused by both inter-population and
      inter-subject variations. METHOD: Six nasal cavity geometries exhibiting diverse
      geometry variations were subjected to steady inhalation flow rate of 15L/min. to
      determine if any consistent flow behaviour could be found. FINDINGS: Despite
      vastly different geometries we were able to identify consistent flow patterns
      including relatively high velocity in the nasal valve region, followed by flow
      continuing predominantly in the inferior half of the airway. We also found
      conformity among models where the inhaled air reached a near-conditioned state by
      the middle of the nasal cavity. Air from the front of the face reached the
      olfactory regions while air from the lateral sides of the face moved through the
      inferior half of the nasal cavity. INTERPRETATION: The ability to predict gross
      flow features provides a baseline flow field to compare against. This contributes
      towards establishing well defined flow predictions and be used as a comparison
      for future larger studies.

PMID- 29074149
TI  - Detection and molecular characterization of Clostridium difficile ST 1 in Buenos
      Aires, Argentina.
AB  - Thirty one C. difficile isolates recovered in 2015 were characterized.
      Nineteen/31 were positive for tcdA/B, among them, 4 isolates were also positive
      for CDT coding genes. Two/4 cdtA/B positives isolates corresponded to ST 1
      resembling BI/NAP1/027/ST 1 strain, while the others corresponded to ST 226 and
      ST 377.

PMID- 29074150
TI  - Adjuvant Chemotherapy Does Not Improve Survival for Lung Cancer With Chest Wall
      Invasion.
AB  - BACKGROUND: The National Comprehensive Cancer Network recommends adjuvant
      chemotherapy (AC) for patients with completely resected (R0) pT3N0M0 non-small
      cell lung cancer (NSCLC) with chest wall invasion. There is minimal evidence to
      support this recommendation. We aimed to determine whether there is a survival
      benefit with AC and if so whether it depends on tumor size. METHODS: Patients who
      had undergone R0 resection for pT3N0M0 NSCLC with chest wall invasion were
      identified in the National Cancer Data Base from 2008 to 2012. Multivariable Cox
      proportional hazards modeling was used to determine independent predictors of
      overall mortality. RESULTS: Of 247 patients, 92 (37.3%) received AC. The median
      tumor size without AC was 42 mm (interquartile range [IQR], 30 to 60 mm) and with
      AC was 56 mm (IQR, 40 to 70 mm; p = 0.003). Median follow-up was 21.7 months
      (IQR, 10.6 to 29.1 months). There was no difference in AC based on tumor grade,
      but the 3-year overall survival for those with well-differentiated or moderately
      differentiated tumors was 68% versus 55% in those with poorly differentiated or
      undifferentiated tumors. Three-year overall survival for the entire cohort was
      59%. There was no difference in overall survival between those who received AC
      and those who did not. The only significant predictor of mortality in both
      univariable and multivariable analyses was poorly or undifferentiated tumor
      grade. CONCLUSIONS: For patients with pT3N0M0 NSCLC with chest wall invasion
      there is no survival benefit with AC, regardless of tumor size or grade, after R0
      resection. Poorly differentiated or undifferentiated tumor grade is an
      independent predictor of mortality.

PMID- 29074151
TI  - Fate of Pneumonectomy Patients Variably Captured by Non-Small Cell Lung Cancer
      Staging System.
AB  - BACKGROUND: Lung cancer patients rely on survival estimates to weigh risks and
      benefits of treatment. However, pneumonectomy-requiring lung cancer may have
      inherent oncologic or physiologic survival implications not captured by the
      current stage classification. Stage-specific survival was evaluated to refine
      survival expectations for patients with pneumonectomy-requiring disease. METHODS:
      The National Cancer Database was queried for treatment-naive patients who
      underwent lobectomy or pneumonectomy for stage I to III non-small cell lung
      cancer between 2004 and 2013. Patients who died within 90 days after resection
      were excluded. Three-way propensity score weighted multivariable Cox models were
      built and incorporated into adjusted 5-year overall survival (OS) curves.
      RESULTS: A total of 79,953 patients met inclusion criteria: 75,708 lobectomies
      (95%) and 4,245 pneumonectomies (5%). Stage I and II patients undergoing right
      pneumonectomy had worse adjusted 5-year OS than patients undergoing left
      pneumonectomy, which was worse than lobectomy (stage I: 55%, 58%, 67%; stage II:
      37%, 44%, 48%; indicating right pneumonectomy, left pneumonectomy, lobectomy).
      Stage III right pneumonectomy patients had worse adjusted 5-year OS; however,
      left pneumonectomy and lobectomy patients were similar (33%, 39%, 40%). A doubly
      robust Cox model identified a similar pattern for mortality risk for stage I and
      II (right pneumonectomy > left > lobectomy); however, stage III right
      pneumonectomy patients had higher mortality risk than lobectomy patients (hazard
      ratio [HR] 1.23, 95% confidence interval [CI]: 1.17 to 1.28, p < 0.001), whereas
      left pneumonectomy was similar to lobectomy (HR 1.02, 95% CI: 0.97 to 1.06, p =
      0.47). CONCLUSIONS: Pneumonectomy-requiring lung cancer embodies a 5-year
      mortality risk not completely captured by the lung cancer staging system. Refined
      survival estimates for pneumonectomy patients may enhance shared decision making
      in this population.

PMID- 29074152
TI  - Patients With Type A Acute Aortic Dissection Presenting With an Abnormal
      Electrocardiogram.
AB  - BACKGROUND: The electrocardiogram (ECG) is often used in the diagnosis of
      patients presenting with chest pain to emergency departments. Because chest pain
      is a common manifestation of type A acute aortic dissection (TAAAD), ECGs are
      obtained in much of this population. We evaluated the effect of particular ECG
      patterns on the diagnosis and treatment of TAAAD. METHODS: TAAAD patients (N =
      2,765) enrolled in the International Registry of Acute Aortic Dissection were
      stratified based on normal (n = 1,094 [39.6%]) and abnormal (n = 1,671 [60.4%])
      findings on presenting ECGs and further subdivided according to specific ECG
      findings. Time data are presented in hours as medians (quartile 1 to quartile 3).
      RESULTS: Patients with ECGs with abnormal findings presented to the hospital
      sooner after symptom onset than those with ECGs with normal findings (1.4 [0.8 to
      3.3] vs 2.0 [1.0 to 3.3]; p = 0.005). Specifically, this was seen in patients
      with infarction with new Q waves or ST elevation (1.3 [0.6 to 2.7] vs 1.5 [0.8 to
      3.3]; p = 0.049). Interestingly, the time between symptom onset and diagnosis was
      longer with infarction with old Q waves (6.7 [3.2 to 18.4] vs 5.0 [2.9 to 11.8];
      p = 0.034) and nonspecific ST-T changes (5.8 [3.0 to 13.8] vs 4.5 [2.8 to 10.5];
      p = 0.002). Surgical mortality was higher in patients with abnormal ECG findings
      (20.6% vs 11.9%, p < 0.001), especially in those with ischemia by ECG (25.7% vs
      16.8%, p < 0.001) and infarction with new Q waves or ST elevation (30.1% vs
      17.1%, p < 0.001). CONCLUSIONS: TAAAD patients presenting with abnormal ECG
      results are sicker, have more in-hospital complications, and are more likely to
      die. The frequency of nonspecific ST-T abnormalities and its association with
      delay in diagnosis and treatment presents an opportunity for practice
      improvement.

PMID- 29074153
TI  - Is Repeat Pulmonary Metastasectomy Indicated for Soft Tissue Sarcoma?
AB  - BACKGROUND: Because recurrence is high after pulmonary metastasectomy (PM) for
      soft tissue sarcoma (STS), repeat PM is commonly performed. Our objective was to
      define the selection criteria for repeat PM among patients experiencing
      recurrence and to identify factors associated with survival. METHODS: We reviewed
      a prospectively maintained database of 539 patients undergoing PM for STS.
      Characteristics of the primary tumor, metastatic disease, treatment, and
      recurrence were examined. Multivariable Cox models were constructed to identify
      factors associated with the likelihood of operative selection after recurrence.
      Overall survival between patients with or without repeat PM was estimated using
      the Kaplan-Meier method, with prognostic factors identified using Cox models.
      Both analyses incorporated propensity score-matching weights. Factors associated
      with survival after repeat PM were assessed with multivariable Cox models among
      patients who underwent repeat PM. RESULTS: After initial PM, 63% of patients (n =
      341) experienced pulmonary recurrence; 141 (41%) underwent repeat PM. Patients
      who were younger (p = 0.033) underwent minimally invasive resection at first PM
      (p = 0.041), had a longer disease-free interval after first PM (p = 0.009), were
      without extrapulmonary disease (p < 0.001), and had fewer nodules on recurrence
      (p < 0.001) were more likely to undergo repeat PM. Comparison between the repeat
      and non-repeat PM groups demonstrated an increased hazard of death among patients
      managed nonoperatively. Factors associated with an increased hazard of death
      after second PM included preoperative chemotherapy (p = 0.008) and R1/R2
      metastasectomy (p < 0.001). CONCLUSIONS: Although operative selection occurs,
      when prognostic factors are controlled for, repeat PM for STS remains
      independently associated with prolonged overall survival.

PMID- 29074154
TI  - Less Is More: Results of a Statewide Analysis of the Impact of Blood Transfusion
      on Coronary Artery Bypass Grafting Outcomes.
AB  - BACKGROUND: Debate persists over the association between blood transfusions,
      especially those considered discretionary, and outcomes after cardiac operations.
      Using data from the Maryland Cardiac Surgery Quality Initiative, we sought to
      determine whether outcomes differed among coronary artery bypass grafting (CABG)
      patients receiving 1 U of red blood cells (RBCs) vs none. METHODS: We used a
      statewide database to review patients who underwent isolated CABG from July 1,
      2011, to June 30, 2016, across 10 Maryland cardiac surgery centers. We included
      patients who received 1 U or fewer of RBCs from the time of the operation through
      discharge. Propensity scoring, using 20 variables to control for treatment
      effect, was performed among patients who did and did not receive a transfusion.
      These two groups were matched 1:1 to assess for differences in our primary
      outcomes: operative death, prolonged postoperative length of stay (>14 days), and
      a composite postoperative respiratory complication of pneumonia or reintubation,
      or both. RESULTS: Of 10,877 patients who underwent CABG, 6,124 (56%) received no
      RBCs (group 1) during their operative hospitalization, and 981 (9.0%) received 1
      U of RBCs (group 2), including 345 of 981 patients (35%) who received a
      transfusion intraoperatively. Propensity score matching generated 937 well
      matched pairs. Compared with group 2, propensity-matched analysis revealed
      significantly greater 30-day survival in group 1 (99% vs 98%, p = 0.02) and
      reduced incidence of prolonged length of stay (3.7% vs 4.0%, p < 0.01).
      CONCLUSIONS: Our collaborative statewide analysis demonstrated that even 1 unit
      of blood was associated with significantly worse survival and longer length of
      stay after CABG. Multiinstitutional quality initiatives may seek to address
      discretionary transfusions and possess the potential to improve patient outcomes.

PMID- 29074155
TI  - Consensus-Derived Coronary Anastomotic Checklist Reveals Significant Variability
      Among Experts.
AB  - BACKGROUND: Surgical skill assessment tools frequently reflect the opinions of
      small groups of surgeons. That raises concerns over their generalizability as
      well as their utilization when applied broadly. A Delphi approach could engage a
      broad group of experts to identify key elements for a checklist assessing
      coronary anastomotic skill, improving generalizability. METHODS: Expert surgeons
      in North America (10 or more years in practice, actively teaching coronary artery
      surgery) were contacted randomly to participate. Consenting surgeons first
      provided items they believed were mandatory when performing a coronary artery
      bypass. These were then entered into a three-round Delphi. Positive consensus was
      reached when 75% or more of participants ranked an item mandatory. RESULTS:
      Sixteen faculty consented to participate. Each participant provided 25 +/- 10
      items. The 407 items provided were condensed, resulting in 146 items in the final
      list, divided into six sections based on the conduct of the operation. Twenty
      three items reached consensus in the first round, 14 in the second, and 3 in the
      third. These 40 items represented only 27% of the initial 146 items. Agreement
      within sections varied widely, from 0% for "management of assistants" to 47% for
      "testing and final steps." CONCLUSIONS: A randomly selected group of experts
      using a Delphi approach can generate a checklist to assess construction of a
      coronary artery bypass. Considerable disagreement among experts regarding what
      steps are mandatory calls into question the generalizability of any locally
      developed checklist.

PMID- 29074156
TI  - Reply to the Letter to the Editor-Clinical prediction rules used to rule out
      endocarditis must be assessed against a sensitive reference standard.

PMID- 29074157
TI  - Next-generation sequencing technologies and their application to the study and
      control of bacterial infections.
AB  - BACKGROUND: With the efficiency and the decreasing cost of next-generation
      sequencing, the technology is being rapidly introduced into clinical and public
      health laboratory practice. AIMS: The historical background and principles of
      first-, second- and third-generation sequencing are described, as are the
      characteristics of the most commonly used sequencing instruments. SOURCES: Peer
      reviewed literature, white papers and meeting reports. CONTENT AND IMPLICATIONS:
      Next-generation sequencing is a technology that could potentially replace many
      traditional microbiological workflows, providing clinicians and public health
      specialists with more actionable information than hitherto achievable. Examples
      of the clinical and public health uses of the technology are provided. The
      challenge of comparability of different sequencing platforms is discussed.
      Finally, the future directions of the technology integrating it with laboratory
      management and public health surveillance systems, and moving it towards
      performing sequencing directly from the clinical specimen (metagenomics), could
      lead to yet another fundamental transformation of clinical diagnostics and public
      health surveillance.

PMID- 29074158
TI  - Staphylococcus aureus colonization during military service: a prospective cohort
      study.
AB  - OBJECTIVES: Staphylococcus aureus colonization leading to skin and soft-tissue
      infections (SSTI) are known challenges in crowded settings such as the military.
      The aim of the study was to establish and compare the prevalence of S. aureus
      colonization in recruits at enrolment and discharge after the first year of
      military service, and to investigate the prevalence of S. aureus SSTI. METHODS:
      All recruits entering first year of military service in January 2013 to be
      stationed at three garrisons in the northern part of Norway were invited to join
      this prospective cohort study. Swabs were taken from nose, throat and perineum.
      Staphylococcus aureus was identified using standard culturing methods.
      Methicillin resistance was determined by a cefoxitin disc diffusion test.
      RESULTS: Of the 923 eligible recruits, 512 were included at enrolment; 265/512
      (52%) were also screened at discharge. Staphylococcus aureus colonization was
      high, and increased significantly during military service (166/265 versus
      224/265, p < 0.001) mainly caused by increase in throat colonization alone or in
      combination with nasal colonization. All S. aureus isolates were susceptible to
      methicillin. SSTI was self-reported in 7/265 (3%) recruits, of which only one was
      confirmed by a military physician. CONCLUSION: Staphylococcus aureus colonization
      increased during military service, but there were few confirmed reports of SSTI.
      Inclusion of throat swab provides important information as ~20% of the recruits
      were only positive in their throat. Further analyses need to be performed to
      investigate if the increase in colonization is caused by specific S. aureus
      stains.

PMID- 29074159
TI  - Association of national and hospital factors to hospitals' alcohol-based handrub
      consumption in Europe: results of the European PROHIBIT study.
AB  - OBJECTIVES: Hand hygiene is considered the most effective way to reduce the
      transmission of (multidrug-resistant) organisms and to prevent healthcare
      associated infections. Hand rubbing with alcohol-based handrub (AHR) has become
      the reference standard for hand hygiene. Data on AHR consumption are easy to
      obtain and can serve as an approximation for hand hygiene compliance. As
      described earlier, AHR consumption varies among European hospitals. In the
      current study the role of various hospital and country indicators for AHR
      consumption is analysed. METHODS: As part of the European Prevention of Hospital
      Infections by Intervention and Training (PROHIBIT) project hospital-based data on
      infection prevention and control (IPC) structure and organization and hospital
      wide AHR consumption were obtained from acute care hospitals. National indicators
      such as income, public health expenditure, national hand hygiene campaigns, IPC
      training and the six Hofstede dimensions were identified. Univariable and
      multivariable linear regression analyses using generalized linear models were
      performed to estimate the association between AHR consumption and indicators at
      both hospital and country levels. RESULTS: Data from 232 hospitals from 22
      European countries were analysed. Multivariate risk factor analysis showed
      independent associations between AHR consumption and private and university
      affiliated hospitals (multiplicative effect, 95% CI: 1.76, 1.21-2.55; and 1.39,
      1.17-1.64, respectively), high-income countries (3.61, 2.94-4.43), and countries
      offering national curricula for the training of IPC nurses (3.77, 2.32-6.13).
      However, no cultural dimension was independently associated with AHR consumption.
      CONCLUSION: Country indicators such as high-income, national training on IPC, and
      hospital type and status are positively associated with AHR consumption in
      Europe.

PMID- 29074160
TI  - Vertebral Cement Leak: How Far Will It Go...?

PMID- 29074162
TI  - Insights into the role of methionine synthase in the universal 13C depletion in O
      and N-methyl groups of natural products.
AB  - Many O-methyl and N-methyl groups in natural products are depleted in 13C
      relative to the rest of the molecule. These methyl groups are derived from the C
      1 tetrahydrofolate pool via l-methionine, the principle donor of methyl units.
      Depletion could occur at a number of steps in the pathway. We have tested the
      hypothesis that methionine biosynthesis is implicated in this depletion by using
      a combined experimental and theoretical approach. By using isotope ratio
      monitoring 13C NMR spectrometry to measure the position-specific distribution of
      13C within l-methionine of natural origin, it is shown that the S-methyl group is
      depleted in 13C by ~200/00 relative to the other positions in the molecule. In
      parallel, we have conducted a basic theoretical analysis of the reaction pathway
      of methionine synthase to assess whether the enzyme cobalamin-independent l
      methionine synthase (EC 2.1.1.14)-that catalyzes the synthesis of l-methionine
      from 5-methyl-tetrahydrofolate and homocysteine-plays a role in causing this
      depletion. Calculation predicts a strong normal 13C kinetic isotope effect
      (1.087) associated with this enzyme. Hence, depletion in 13C in the S-methyl of l
      methionine during biosynthesis can be identified as an important factor
      contributing to the general depletion seen in many O-methyl and N-methyl groups
      of natural products.

PMID- 29074161
TI  - SCORE2 Report 5: Vision-Related Function in Patients With Macular Edema Secondary
      to Central Retinal or Hemiretinal Vein Occlusion.
AB  - PURPOSE: To describe baseline vision-related function, measured with the National
      Eye Institute Visual Function Questionnaire (NEI VFQ-25), in patients with
      macular edema secondary to central retinal vein occlusion (CRVO) or hemiretinal
      vein occlusion (HRVO) in the Study of COmparative Treatments for REtinal Vein
      Occlusion 2 (SCORE2); evaluate the baseline relationship between NEI VFQ-25
      scores with visual acuity letter score (VALS) and central retinal thickness; and
      compare baseline NEI VFQ-25 scores in SCORE2 participants with those in normal
      vision reference populations and patients in other retinal vein occlusion trials.
      DESIGN: Multicenter, noninferiority randomized controlled trial. METHODS: SCORE2
      was designed to assess whether intravitreal bevacizumab is noninferior to
      intravitreal aflibercept for treatment of decreased vision attributable to
      macular edema owing to CRVO or HRVO. SCORE2 enrolled 362 participants, including
      305 with CRVO and 57 with HRVO. Analyses were of cross-sectional baseline data.
      The main outcome measures were baseline NEI VFQ-25 composite and subscale scores.
      RESULTS: SCORE2 participants' baseline NEI VFQ-25 composite and subscale scores
      are significantly lower compared with 3 normal-vision reference populations (P <
      .01; except for ocular pain score) and similar to patients in other retinal vein
      occlusion clinical trials. Baseline VALS in the better eye was correlated with
      baseline NEI VFQ-25 composite and subscale scores of general vision, near
      activities, role difficulties, dependency, and color vision, with correlations
      ranging from 0.19 to 0.26 (P < .05 for each score). CONCLUSIONS: CRVO and HRVO
      patients in SCORE2 had significantly worse baseline patient-reported vision
      related function than normal vision populations, despite the disease being
      primarily unilateral with typically excellent vision in the fellow eye.

PMID- 29074163
TI  - Incorporation of antibacterial agent derived deep eutectic solvent into an active
      dental composite.
AB  - OBJECTIVE: To incorporate an antibacterial agent derived deep eutectic solvent
      (DES) into a dental resin composite, and investigate the resulting mechanical
      properties and antibacterial effects. METHOD: The DES was derived from
      benzalkonium chloride (BC) and acrylic acid (AA) and was incorporated into the
      dental resin composite through rapid mixing. A three-point bending test was
      employed to measure the flexural strength of the composite. An agar diffusion
      test was used to investigate antibacterial activity. Artificial (accelerated)
      aging was undertaken by immersing the composites in buffer solutions at an
      elevated temperature for up to 4 weeks. UV-vis spectrophotometry and NMR analysis
      were conducted to study BC release from the composite. Finally, the
      biocompatibility of the composite materials was evaluated using osteoblast cell
      culture for 7 days. Results were compared to those of a control composite which
      contained no BC. RESULT: The DES-incorporated composite (DES-C) displayed higher
      flexural strength than a similar BC-incorporated composite BC (BC-C) for the same
      level of BC. The inclusion of BC conferred antibacterial activity to both BC
      containing composites, although BC-C produced larger inhibition halos than DES-C
      at the same loading of BC. Control composites which contained no BC showed
      negligible antibacterial activity. After artificial aging, the DES-C composite
      showed better maintenance of the mechanical properties of the control compared
      with BC-C, although a decrease was observed during the three-point bending test,
      particularly upon storage at elevated temperatures. No BC release was detected in
      the aged solutions of DES-C, whereas the BC-C showed a linear increase in BC
      release with storage time. Significantly, cell viability results indicated that
      DES-C has better biocompatibility than BC-C. SIGNIFICANCE: The incorporation of a
      BC-based DES into a dental resin composite provides a new strategy to develop
      antibacterial dental materials with better biocompatibility and longer effective
      lifetimes without sacrificing the intrinsic mechanical properties of the
      composite structure.

PMID- 29074165
TI  - Early life undernutrition and adult height: The Dutch famine of 1944-45.
AB  - Current research shows strong associations between adult height and several
      positive outcomes such as higher cognitive skills, better earning capacity,
      increased chance of marriage and better health. It is therefore relevant to
      investigate the determinants of adult height. There is mixed evidence on the
      effects of undernutrition during early life on adult height. Therefore, our study
      aims at assessing the impact of undernutrition during gestation and at ages
      younger than 15 on adult height. We used data from the Longitudinal Aging Study
      Amsterdam. Exposure to undernutrition was determined by place of residence during
      the Dutch famine during World War II. Included respondents were born between 15
      May 1930 and 1 November 1945 and lived in the northern part of the Netherlands
      during the famine period (n=1008). Exposure data was collected using interviews
      and questionnaires and adult height was measured. Exposed and non-exposed
      respondents were classified in the age categories pregnancy- age 1 (n=85), age 1
      5 (n=323), age 6-10 (n=326) or puberty (age 11-15, n=274). Linear regression
      analyses were used to test the associations of adult height with exposure. The
      robustness of the regression results was tested with sensitivity analyses. In the
      models adjusted for covariates (i.e., number of siblings, education level of
      parents, and year of birth) and stratified by gender, adult height was
      significantly shorter for females exposed at ages younger than 1 (-4.45cm [-7.44-
      1.47]) or at ages younger than 2 (-4.08cm [-7.20--0.94]). The results for males
      were only borderline significant for exposure under age 1 (-3.16 [-6.82-0.49])
      and significant for exposure under age 2 (-4.09cm [-7.20--0.96]). Exposure to the
      Dutch famine at other ages was not consistently significantly associated with
      adult height. In terms of public health relevance, the study's results further
      underpin the importance of supporting pregnant women and young parents exposed to
      undernutrition.

PMID- 29074164
TI  - Defective regulation of L1 endogenous retroelements in primary Sjogren's syndrome
      and systemic lupus erythematosus: Role of methylating enzymes.
AB  - OBJECTIVE: To investigate whether altered DNA methylation contributes to the
      inappropriate expression of LINE-1 (L1) retroelements in primary Sjogren's
      syndrome (SS) and systemic lupus erythematosus (SLE). METHODS: Minor salivary
      glands (MSG) were obtained from 42 patients with primary SS [23 without adverse
      predictors for lymphoma development (SS-low risk), 7 SS-high risk and 12
      complicated by B-cell lymphoma (SS-lymphoma)] and 17 sicca controls (SC).
      Additionally, kidney biopsy specimens and PBMCs were obtained from 23 and 73
      lupus patients, respectively. Relative mRNA expression was quantified for full
      length L1 transcripts, along with mediators of methylation. In an independent set
      of 44 MSG samples (11 SS-low risk, 10 SS-high risk, 15 SS-lymphoma and 8 SC),
      methylation levels of the L1 promoter were determined by bisulphite
      pyrosequencing. RESULTS: A strong positive correlation was demonstrated between
      L1 transcripts and gene products that mediate de novo and constitutive DNA
      methylation, DNA methyltransferase (DNMT)3B, DNMT1, and methyl CpG binding
      protein 2 (MeCP2), in both SS MSG and lupus renal tissues. A significant negative
      correlation was observed between expression of L1 and lymphoid-specific helicase
      (LSH, encoded by HELLS) in both SS MSG and SLE kidney tissues, as well as between
      DNMT3A transcripts and L1 expression in SLE kidney tissues and PBMCs. Reduced
      levels of L1 promoter methylation along with increased DNMT3B, DNMT1, and MeCP2,
      but reduced LSH levels were detected in SS-low risk patients compared to both SS
      lymphoma and SC. The SS-lymphoma group was also characterized by a profound
      decrease of MeCP2 and DNMT3B compared to SC. CONCLUSION: Our data support a
      contributory role of altered methylation mechanisms in the pathogenesis of
      systemic autoimmune disorders and related lymphoproliferative processes and
      suggest that LSH and DNMT3A should be investigated as candidate upstream
      mediators of decreased L1 promoter methylation and increased L1 expression.

PMID- 29074166
TI  - Association Between High Environmental Heat and Risk of Acute Kidney Injury Among
      Older Adults in a Northern Climate: A Matched Case-Control Study.
AB  - BACKGROUND: An association between high heat and acute kidney injury (AKI) has
      been reported in warm climates. However, whether this association generalizes to
      a northern climate, with more variable temperatures, is unknown. STUDY DESIGN:
      Matched case-control study. SETTING & PARTICIPANTS: Our study focused on older
      adults (mean age, 80 years) in the northern climate of Ontario, Canada. 52,913
      case patients who had a hospital encounter with AKI in April through September
      2005 to 2012 were matched with 174,222 controls for exact date, age, sex, rural
      residence, income, and history of chronic kidney disease. PREDICTOR: Heat periods
      were defined as 3 consecutive days exceeding the 95th percentile of area-specific
      maximum temperature. OUTCOMES: Hospital encounter (inpatient admission or
      emergency department visit) with a diagnosis of AKI. MEASUREMENTS: ORs (95% CIs)
      were used to assess the association between heat periods and AKI. To quantify the
      effect in absolute terms, we multiplied the population incidence rate of AKI in
      the absence of heat periods by our adjusted OR (an approximate of relative risk).
      RESULTS: Heat periods were significantly associated with higher risk for AKI
      (adjusted OR, 1.11; 95% CI, 1.00-1.23). Heat periods in absolute terms were
      associated with an additional 182 cases of AKI per 100,000 person-years during
      the warm season. LIMITATIONS: We did not know how long persons were outside or if
      they had access to air conditioning. CONCLUSIONS: In a northern climate, periods
      of higher environmental heat were associated with a modestly higher risk for
      hospital encounter with AKI among older adults.

PMID- 29074167
TI  - Direct antiviral treatment in patients with hepatitis C virus: Implementation of
      a nurse telephone consultation.
AB  - The treatment of chronic hepatitis C with direct action antivirals has led to a
      radical change in the management of patients. The elderly or people with
      morbidities, for whom it was previously contraindicated, are currently candidates
      for this treatment due to its being well tolerated and safe. The nursing visit at
      the beginning of treatment is essential to reinforce adherence, to educate on the
      management of adverse effects, to resolve doubts and to emphasise the importance
      of pharmacological interactions, in order to promote correct therapeutic
      compliance. However, due to the new communication tools, it is possible to convey
      healthcare services without requiring the physical presence of the patient in the
      medical centre. The telephone has become a routine and indispensable work tool
      for the nursing professional. This paper describes the pilot test that was
      performed with 38 patients, previously selected, whose nursing visit at the
      beginning of treatment was by telephone instead of face-to-face, in order to
      evaluate the implementation of the telephone nurse consultation, for patients who
      started treatment with direct antivirals for the hepatitis C virus.

PMID- 29074168
TI  - Intervention of the hospital midwife in the case of a pregnant women who had
      undergone female genital mutilation. A case study.
AB  - Female genital mutilation, condemned by all UN member countries has spread
      throughout the world as a result of migratory flows and is practiced under the
      guise of a custom, tradition or culture. In Spain, it is punishable as a personal
      injury offence under the current penal code. A clinical case study reviewedthe
      main actions of the midwife in this kind of injury in a pregnant woman during
      labour. The data collected from the physical examination and the midwife's
      assessment according to the Virginia Henderson model are presented and a complete
      care plan developed. From the case it can be concluded that in the hospital area,
      midwives can and should reinforce and complete the work with these women and
      their families, of informing, educating and reinforcing the decision not to
      mutilate. This work should have been started in, the health centre.

PMID- 29074170
TI  - Need for expanded HPV genotyping for cervical screening.
AB  - The focus for HPV genotyping has largely been on types 16 and 18, based on their
      high prevalence in cervix cancer. However screening is focussed on the detection
      of high grade precursor lesions (CIN3 and CIN2), where other types have a greater
      role. While HPV16 retains its high predictive value in this context, HPV31 and
      especially HPV33 emerge as important types with higher positive predictive values
      (PPVs) than HPV18. Additionally full typing indicates that types 39, 56, 59 and
      68 have much lower PPVs than types 16, 18, 31, 33, 35, 45, 51, 52 and 58 and they
      should be considered as 'intermediate risk' types, whereas type 66 should not be
      treated as having an increased risk. Available data are summarized to support
      this view.

PMID- 29074171
TI  - Knowledge, attitudes, and perception towards human papillomavirus among
      university students in Pakistan.
AB  - This cross-sectional study comprises a questionnaire-based survey regarding
      knowledge about human papillomavirus and its vaccine among students in different
      educational fields at public and private universities in the city of Lahore in
      Pakistan. A 26-item questionnaire was used to attain the objective of this study.
      The reliability of this tool was assessed using Cronbach's alpha (0.79) and the
      Kaiser-Meyer-Olkin value was 0.827. The response rate to the survey was 78.0%, of
      whom the majority (74.9%) were females and 308 (79%) were single (median age=23
      years). While assessing the respondents' knowledge about HPV, 223(57%) students
      reported that they had already heard of HPV (human papillomavirus) and nearly 215
      (55%) reported that HPV causes cervical cancer and can infect both men and women.
      Gender and field of study were two main factors found influencing the
      respondents' knowledge about HPV. Moreover, students' understanding about the
      mode of transmission of HPV was cursory: 40.51% said they did not know how HPV is
      transmitted, 133 (34.10%) stated that HPV spreads through the exchange of bodily
      fluids, and 22 (5.64%) selected cough/sneezing. In terms of prevention, 175
      (44.87%) students stated that HPV can be prevented by vaccination, 30.0% reported
      sexual abstinence, 21.54% using condoms, and nearly 5.38% disclosed use of
      antibiotics. Addressing the knowledge of students regarding HPV vaccine, nearly
      53% stated there is no vaccine against HPV and almost 64% rejected the statement
      that HPV vaccine prevents cervical cancer. In addition, students reported that
      they will be more than willing to get vaccinated for HPV if their physician
      recommend them (RII=0.74) followed by parents (RII=0.69). The results of this
      study revealed a poor understanding among respondents about the health problems
      associated with HPV, its prevention, modes of transmission and arability of HPV
      vaccine in Pakistan.

PMID- 29074169
TI  - Monitoring the impact of HPV vaccine in males-Considerations and challenges.
AB  - In this article, we examine the issues involved if national or sub-national
      programs are considering extending post HPV vaccine introduction monitoring to
      include males. Vaccination programs are now being extended to include males in
      some countries, in order to improve population level HPV infection control and to
      directly prevent HPV-related disease in males such as anogenital warts and anal
      cancers. Coverage and adverse events surveillance are essential components of
      post-vaccination monitoring. Monitoring the impact of vaccination on HPV
      infection and disease in men raises some similar challenges to monitoring in
      females, such as the long time frame until cancer outcomes, and also different
      ones given that genital specimens suitable for monitoring HPV prevalence are not
      routinely collected for other diagnostic or screening purposes in males. Thus,
      dedicated surveillance strategies must be designed; the framework of these may be
      country-specific, dependent upon the male population that is offered vaccination,
      the health care infrastructure and existing models of disease surveillance such
      as STI networks. The primary objective of any male HPV surveillance program will
      be to document changes in the prevalence of HPV infection and disease due to
      vaccine targeted HPV types occurring post vaccination. The full spectrum of
      outcomes to be considered for inclusion in any surveillance plan includes HPV
      prevalence monitoring, anogenital warts, potentially pre-cancerous lesions such
      as anal squamous intraepithelial lesions (SIL), and cancers. Ideally, a
      combination of short term and long term outcome measures would be included.
      Surveillance over time in specific targeted populations of men who have sex with
      men and HIV-infected men (populations at high risk for HPV infection and
      associated disease) could be an efficient use of resources to demonstrate impact.

PMID- 29074172
TI  - Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East
      Italy.
AB  - OBJECTIVES: To investigate the frequency of Human papillomavirus (HPV)-driven
      head and neck squamous cell carcinoma (HNSCC) among patients living in North-East
      Italy, by assessing HPV-DNA positivity in all tumors and additional markers
      whenever possible. MATERIAL AND METHODS: HPV types, viral load, viral RNA,
      HPV16/18 E6 protein and p16INK4a and pRb expression were determined in primary
      tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was
      analyzed in 102 patients. RESULTS: Tumor HPV-DNA prevalence was 8.5% overall
      (21/247) and 27% in oropharynx (17/63). HPV16 accounted for 95% of all HPV types
      found. Among HPV-DNA+ tumors, type-concordant HPV E6*I RNA prevalence was 79%.
      HPV DNA+ RNA+ tumors showed high viral load, up-regulated p16INK4a, down
      regulated pRb and presence of HPV16 E6 protein. Eight cases showed tumor-specific
      HPV seropositivity, all type-concordant with the tumor. Tumors were defined as
      HPV-driven when positive for HPV-DNA plus 2 additional HPV transformation-related
      markers. CONCLUSION: Relative prevalence of HPV-driven tumors (14 HPV16, 1 HPV58)
      was 6% overall and 20% among oropharyngeal cancers. In the oropharynx the HPV
      driven group showed a trend for better survival versus the HPV-negative group.
      The relative prevalence of HPV-driven oropharyngeal cancer is low in North-East
      Italy as compared to Western and Northern Europe.

PMID- 29074174
TI  - Human papillomavirus prevalence and type distribution in urine samples from
      Norwegian women aged 17 and 21 years: A nationwide cross-sectional study of three
      non-vaccinated birth cohorts.
AB  - BACKGROUND: The aim of the current study was to assess the HPV prevalence in
      unscreened and unvaccinated young women living in Norway, to provide important
      baseline data for early estimation of the impact of the HPV vaccination program.
      METHODS: A total of 13,129 self-sampled urine samples from two complete birth
      cohorts of 17-year old women born in 1994 and 1996 and one third of a birth
      cohort of 21-year old women born in 1990, were analysed for the presence of 37
      HPV types using PCR and a DNA hybridization technique. RESULTS: In the two birth
      cohorts of 17-year old women, HPV was detected in 19.9% (95% CI 18.8-20.9) and
      15.4% (95% CI 14.5-16.3), respectively. High-risk HPV types were detected in
      11.2% (95% CI 10.3-12.0) and 7.6% (95% CI 6.9-8.2), respectively, while vaccine
      types were detected in 7.4% (95% CI 6.7-8.1) and 6.0% (95% CI 5.4-6.6),
      respectively. Among the 21-year old women HPV was detected in 45.4% (95% CI 42.9
      47.8), whereas high-risk types were detected in 29.8% (95% CI 27.5-32.0). Vaccine
      types (HPV 6, 11, 16, 18) were detected in 16.2% (95% CI 14.4-18.1). CONCLUSION:
      This large population based study confirms that HPV testing in urine samples is
      easy and highly feasible for epidemiological studies and vaccine surveillance in
      young women. HPV was very common and a broad spectrum of HPV types was
      identified. Differences in HPV prevalence was seen both between age groups and
      between the two birth cohorts of 17-year old women.

PMID- 29074173
TI  - Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence
      among children: Design, methods and preliminary results of the HERITAGE study.
AB  - Perinatal route of transmission of human papillomavirus (HPV) has been
      demonstrated in several small studies. We designed a large prospective cohort
      study (HERITAGE) to better understand perinatal HPV. The objective of this
      article is to present the study design and preliminary data. In the first phase
      of the study, we recruited 167 women in Montreal, Canada, during the first
      trimester of pregnancy. An additional 850 are currently being recruited in the
      ongoing phase. Cervicovaginal samples were obtained from mothers in the first
      trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the
      third trimester for HPV-positive mothers). Placental samples were also taken for
      HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were
      collected for HPV DNA testing in children of HPV-positive mothers at every 3-6
      months from birth until 2 years of age. Blood samples were collected in mother
      and children for HPV serology testing. We found a high prevalence of HPV in
      pregnant women (45%[95%CI:37-53%]) and in placentas (14%[8-21%]). The proportion
      of HPV positivity (any site) among children at birth/3-months was 11%[5-22%]. HPV
      was detected in children in multiple sites including the conjunctiva (5%[10
      14%]). The ongoing HERITAGE cohort will help provide a better understanding of
      perinatal HPV.

PMID- 29074175
TI  - Novel canine papillomavirus type 18 found in pigmented plaques.

PMID- 29074177
TI  - High specific immune response to a bivalent anti-HPV vaccine in HIV-1-infected
      men in Sao Paulo, Brazil.
AB  - INTRODUCTION: Infection with Human papillomavirus (HPV) has been reported as one
      of the most prevalent agent sexually transmitted diseases, but its true
      prevalence in men is not precisely known, mainly due to the near absence of
      symptoms. Moreover, few studies evaluating the post-vaccination immune response
      have been performed to date in men, hence the hypotheses tested in this study can
      be important to enable a better understanding of both the immunopathogenesis and
      the response to vaccination in HIV-infected patients, and to help in the
      elaboration of strategies of vaccination against HPV in the HIV-infected
      population. OBJECTIVES: To analyze the specific response to antigens of HPV
      vaccine in HIV-infected men. METHODS: A total of 25 HIV-infected male patients
      who met the inclusion criteria during the data collection period were vaccinated;
      however, six (30%) had anti-HPV at baseline, and were not considered further in
      the analysis. Therefore, 19 HIV-infected individuals were included in the study,
      along with five healthy, HPV-seronegative controls. RESULTS: Patients infected
      with HIV-1 were subdivided into two groups, A and B, according to their T CD4
      cells count at the time of vaccination, namely: Group A: CD4>500; Group B:
      CD4<500. The proportion of seroconversion after immunization with three doses of
      a bivalent anti-HPV vaccine was 92%. CONCLUSION: HIV-infected patients as well as
      HIV negative controls responded to anti-HPV vaccination, regardless of their T
      CD4 cells count and HIV plasma viral load. These results demonstrate that anti
      HPV immunization in HIV-infected males is effective and should be encouraged,
      thus helping to decrease the risk of infection, mortality and morbidity of
      diseases associated with HPV in men.

PMID- 29074176
TI  - Validation of the vaccine conspiracy beliefs scale.
AB  - BACKGROUND: Parents' vaccine attitudes influence their decision regarding child
      vaccination. To date, no study has evaluated the impact of vaccine conspiracy
      beliefs on human papillomavirus vaccine acceptance. The authors assessed the
      validity of a Vaccine Conspiracy Beliefs Scale (VCBS) and determined whether this
      scale was associated with parents' willingness to vaccinate their son with the
      HPV vaccine. METHODS: Canadian parents completed a 24-min online survey in 2014.
      Measures included socio-demographic variables, HPV knowledge, health care
      provider recommendation, Conspiracy Mentality Questionnaire (CMQ), the seven-item
      VCBS, and parents' willingness to vaccinate their son at two price points.
      RESULTS: A total of 1427 Canadian parents completed the survey in English (61.2%)
      or French (38.8%). A Factor Analysis revealed the VCBS is one-dimensional and has
      high internal consistency (alpha=0.937). The construct validity of the VCBS was
      supported by a moderate relationship with the CMQ (r=0.44, p<0.001). Hierarchical
      regression analyses found the VCBS is negatively related to parents' willingness
      to vaccinate their son with the HPV vaccine at both price points ('free' or
      '$300') after controlling for gender, age, household income, education level, HPV
      knowledge, and health care provider recommendation. CONCLUSIONS: The VCBS is a
      brief, valid scale that will be useful in further elucidating the correlates of
      vaccine hesitancy. Future research could use the VCBS to evaluate the impact of
      vaccine conspiracies beliefs on vaccine uptake and how concerns about vaccination
      may be challenged and reversed.

PMID- 29074178
TI  - Factors affecting HPV vaccine acceptance in west Austria: Do we need to revise
      the current immunization scheme?
AB  - BACKGROUND: Austria introduced a school-based gender-neutral human papillomavirus
      (HPV) immunization program in February 2014. In order to assure high coverage,
      factors influencing acceptance of the vaccine need to be identified. In this
      study we aim to assess parents' attitude and related socio-demographic factors in
      relation to the newly implemented gender-neutral, school-based HPV Immunization
      program. METHODS: Parents of 4th grade school children in 20 randomly selected
      primary schools were asked to fill out questionnaires on socio-demographic
      factors and on the level of information and attitude towards HPV infection and
      HPV vaccine. RESULTS: A total of 439 parents with 449 vaccine eligible children
      participated in the study. Fifty nine percent of vaccine eligible girls and 51.8%
      of eligible boys received the first dose of the vaccine. Fear of side effects and
      child being too young for the vaccine were the most commonly cited reasons by
      parents electing not to let child receive the vaccine. Children who had received
      other school-based vaccines have more than fifteen times higher probability of
      receiving HPV vaccine. To have received HPV-related information from physicians
      positively influenced vaccine acceptance (OR (95% CI)=1.60 (1.06-2.43)). Higher
      paternal (fathers') educational status significantly increased the chances of a
      male child to be HPV vaccinated (OR (95% CI)=2.45 (1.29-4.78)). CONCLUSION:
      Despite the efforts to provide HPV vaccine free-of-costs and as a school-based
      program, the study found that a significant proportion of vaccine eligible
      children failed to receive the vaccine. Involvement front line physicians and men
      with higher educational status may be utilised by public health policy makers in
      the effort to increase awareness. For a better acceptability of the vaccine,
      there is a need to consider lifting the age of "eligibility" for the school-based
      vaccination program.

PMID- 29074180
TI  - Development of World Health Organization (WHO) recommendations for appropriate
      clinical trial endpoints for next-generation Human Papillomavirus (HPV) vaccines.
AB  - The World Health Organization (WHO) serves as a key organization to bring
      together experts along the continuum of vaccine development and regulatory
      approval, among its other functions. Using the revision of WHO's guidelines on
      prophylactic human papillomavirus (HPV) vaccine as an example, we describe the
      process by which (1) a need to revise the guidelines was identified; (2) a group
      of stakeholders with complementary expertise and key questions were identified;
      (3) a scientific review was conducted; (4) consensus on revisions was achieved;
      (5) guidelines were updated, reviewed widely, and approved. This multi-year
      process resulted in the consensus that regulatory agencies could consider
      additional endpoints, such as persistent HPV infection or immune equivalence,
      depending on the design of the HPV vaccine trials. Updating the guidelines will
      now accelerate vaccine development, reduce costs of clinical trials, and lead to
      faster regulatory approval.

PMID- 29074179
TI  - HPV vaccination intention among male clients of a large STI outpatient clinic in
      Amsterdam, the Netherlands.
AB  - We explored HPV vaccination intention and its determinants among male clients of
      the sexually transmitted infections (STI) clinic in Amsterdam. In 2015, male
      clients aged >=18 years were invited to complete a web-based questionnaire
      regarding HPV vaccination intention and socio-psychological determinants.
      Determinants (scale -3 to +3) were assessed with linear regression, stratified
      for men who have sex with men (MSM) (including men who have sex with men and
      women) and men who only have sex with women (MSW). Additionally, we explored the
      effect of out-of-pocket payment on intention. Of 1490 participants (median age 33
      years [IQR:25-44]), 1,053(71%) were MSM. HPV vaccination intention was high (mean
      1.68, 95%CI:1.55-1.81 among MSW; mean 2.35, 95%CI:2.29-2.42 among MSM). In
      multivariable analyses, socio-psychological determinants had similar effects on
      intention in both groups (R2=0.70 among MSW; R2=0.68 among MSM), except for
      subjective norms, self-efficacy, and HPV knowledge (significantly stronger
      associations among MSW). HPV vaccination intention decreased significantly when
      vaccination would require out-of-pocket payment; intention was negative at the
      current list price (?350). HPV vaccination intention among male clients of the
      Amsterdam STI-clinic is high and variance in intention was mostly be explained by
      socio-psychological factors. Out-of-pocket payment had a strong negative effect
      on HPV vaccination intention.

PMID- 29074181
TI  - Challenges in educating women about human papillomavirus (HPV) and HPV screening
      test results: Experience from an HPV demonstration project in North-Eastern
      Thailand.

PMID- 29074183
TI  - Clinical and analytical performance of the BD OnclarityTM HPV assay for detection
      of CIN2+ lesions on SurePath samples.
AB  - BACKGROUND: The novel BD OnclarityTM HPV assay (Onclarity) on the BD ViperTM LT
      system (BD Diagnostics, Sparks, MD), detects E6/E7 DNA from 13 high-risk HPV
      genotypes and HPV66. We compared the analytical and clinical performance of the
      Onclarity Assay to that of Hybrid Capture 2 and LINEAR ARRAY using adjudicated
      histological outcomes from Danish women referred for colposcopy. METHODS: 276
      women from Copenhagen, Denmark were referred for colposcopy with abnormal
      cytology and/or a positive HPV test. Two samples for HPV analysis were taken in
      BD SurePathTM and in the BD cervical brush diluent (CBD) media. ClinicalTrial
      gov. identifier: NCT01671462, Ethical Approval: H-4-2012-070. RESULTS: Histology
      was normal in 84 (31%) women, 70 (26%) had CIN1, 47 (17%) CIN2, and 68 (25%) had
      CIN3. The Onclarity assay detected 67 out of 68 (99%) >=CIN3 and 113/115 (98%)
      >=CIN2. The specificities for <CIN2 were 21%, 17%, and 22%, for HC2, Onclarity
      and LA, respectively. CONCLUSION: Overall, the Onclarity HPV assay performed well
      on SurePath LBC and CBD media, with clinical sensitivity and specificity matching
      those of HC2 and LA.

PMID- 29074184
TI  - HPV distribution in cervical cancer in Portugal. A retrospective study from 1928
      to 2005.
AB  - OBJECTIVES: To determine human papillomavirus (HPV) types in invasive cervical
      cancer in Portugal. METHODS: Cases diagnosed at the Instituto Portugues de
      Oncologia de Lisboa de Francisco Gentil from the year 1928 to 2005 were selected
      for HPV DNA detection and genotyping using SPF10/DEIA/LiPA25 system. RESULTS: Of
      the 1214 samples that were considered appropriate for HPV detection, 714 (58.8%;
      95% CI: 56.0-61.6%) were positive for HPV DNA. This detection rate varied being
      lower in the first 3 decades (31.3%; 50.1%; 46.5%) and higher in the last decades
      (77.4-95.1%). This difference was due probably to the fixative used in the first
      three decades. The five most common types identified among HPV positive cases
      were HPV16 (58.2%), HPV18 (9.2%), HPV33 (6.2%), HPV45 (4.7%) and HPV31 (4.4%).
      Multiple infections were detected in 2.8% of the cases. HPV16 and 18 accounted
      for 67.4% of infections. There were no statistically significant changes of these
      types over the studied period. An increase at patient's age at diagnosis was
      observed in the last decades (p<0.001). CONCLUSION: HPV16 and 18 accounts for
      almost 70% of cervical cancers in all 9 decades studied and support data that
      effective vaccination against these 2 types will reduce the cervical burden in
      Portuguese women.

PMID- 29074185
TI  - What explains the different rates of human papillomavirus vaccination among
      adolescent males and females in the United States?
AB  - PURPOSE: To identify factors that explain differences in HPV vaccination rates
      for male and female adolescents and to determine self-reported barriers by
      parents affecting vaccination decisions. METHODS: The sample included adolescents
      13-17 years old with a vaccination record documented in the 2012 and 2013
      National Immunization Survey-Teen dataset. A logistic regression model was
      developed with 13 socio-demographic factors and survey year, along with
      significant interaction pairs with gender. RESULTS: Subjects included 20,355 and
      18,350 adolescent boys and girls, respectively. About half of the females (56%)
      received at least one dose of HPV vaccine, compared to 28% of males. Several
      factors differed between males and females, including higher vaccination rates
      among non-Hispanic Black males and lower vaccination rates for non-Hispanic Black
      females compared to Whites; and a stronger association with health care provider
      recommendation among males. The most common parental reasons for not vaccinating
      their children included 'not recommended by a health care provider' for males
      (24%), and 'unnecessary' for females (18%). CONCLUSION: We found a significant
      gender interaction with several socio-demographic variables in predicting
      vaccination uptake. These gender differences may be partially an artifact of
      timing, because male vaccination became routine approximately five years after
      female vaccination.

PMID- 29074186
TI  - Xpert human papillomavirus test is a promising cervical cancer screening test for
      HIV-seropositive women.
AB  - : This study investigated the performance of Cepheid Xpert human papillomavirus
      (HPV) assay in South African human immunodeficiency virus (HIV)-infected women
      and compared its performance with that of hybrid capture-2 (hc2). METHODS: Stored
      cervical specimens from HIV-infected women that had previously been tested using
      hc2 were tested using Xpert. RESULTS: The overall HR-HPV prevalence was found to
      be 62.0% (720/1161) by Xpert and 61.2% (711/1161) by hc2. 13.6% (158/1161) were
      HPV16 positive, 18.8% (218/1161) were HPV18/45, 37.3% (434/1161) were
      HPV31/33/35/52/58, 12.7% (147/1161) were HPV51/59 and 23.3% (270/1161) were
      HPV39/68/56/66. Overall agreement with hc2 was 90%; Cohen's kappa was 0.78 (95%
      CI 0.74-0.82) indicating substantial agreement. Detection of HPV16, HPV18/45, and
      HPV31/33/35/52/58 were independently associated with cervical intraepithelial
      neoplasia (CIN)-2+ (P<0.0001 for each); while HPV51/59 and HPV39/68/56/66 were
      not. Women infected with HPV16, HPV18/45 or HPV31/33/35/52/58 were found to have
      significantly higher amounts of HPV DNA detected for those with CIN2+ compared to
      those without CIN2+, P<0.0001 for each. Xpert and hc2 were similarly sensitive
      (88.3% and 91.5%, respectively) and specific (48.4% and 51.0%) for CIN2+ and CIN3
      (sensitivity: 95.8% and 97.9%; specificity: 41.4% and 42.8%). CONCLUSIONS: Xpert
      is a promising screening test in HIV-infected women that performs similarly to
      hc2.

PMID- 29074187
TI  - Human papillomavirus detection in cervical neoplasia attributed to 12 high-risk
      human papillomavirus genotypes by region.
AB  - BACKGROUND: We estimated the proportion of cervical intraepithelial neoplasia
      (CIN) cases attributed to 14 HPV types, including quadrivalent (qHPV)
      (6/11/16/18) and 9-valent (9vHPV) (6/11/16/18/31/33/45/52/58) vaccine types, by
      region METHODS: Women ages 15-26 and 24-45 years from 5 regions were enrolled in
      qHPV vaccine clinical trials. Among 10,706 women (placebo arms), 1539 CIN1, 945
      CIN2/3, and 24 adenocarcinoma in situ (AIS) cases were diagnosed by pathology
      panel consensus. RESULTS: Predominant HPV types were 16/51/52/56 (anogenital
      infection), 16/39/51/52/56 (CIN1), and 16/31/52/58 (CIN2/3). In regions with
      largest sample sizes, minimal regional variation was observed in 9vHPV type
      prevalence in CIN1 (~50%) and CIN2/3 (81-85%). Types 31/33/45/52/58 accounted for
      25-30% of CIN1 in Latin America and Europe, but 14-18% in North America and Asia.
      Types 31/33/45/52/58 accounted for 33-38% of CIN2/3 in Latin America (younger
      women), Europe, and Asia, but 17-18% of CIN2/3 in Latin America (older women) and
      North America. Non-vaccine HPV types 35/39/51/56/59 had similar or higher
      prevalence than qHPV types in CIN1 and were attributed to 2-11% of CIN2/3.
      CONCLUSIONS: The 9vHPV vaccine could potentially prevent the majority of CIN1-3,
      irrespective of geographic region. Notwithstanding, non-vaccine types
      35/39/51/56/59 may still be responsible for some CIN1, and to a lesser extent
      CIN2/3.

PMID- 29074189
TI  - Ethnic background and human papillomavirus vaccine uptake in Denmark: A
      countrywide retrospective cohort study including 274,154 women aged 19-28 years.
AB  - AIM: We examined ethnicity-related differences in the uptake of a temporary free
      of-charge HPV vaccine (HPVV) catch-up programme offered in Denmark from August
      2012 to December 2013 to women born from 1985-1992 and compared it with the
      previous self-payment system in place. METHODS: We conducted a nationwide
      retrospective cohort study. We performed logistic regression analyses to examine
      the relationship between ethnic background and HPV vaccine (HPVV) programme
      initiation. RESULTS: The free programme increased the vaccination uptake from 16%
      to 75%. Descendants (Denmark-born women with both parents of foreign origin) and
      immigrants in Denmark for more than 5 years were less likely to initiate the free
      HPVV programme than Denmark-born women ((aOR=0.56; 95% CI: 0.54-0.59) and
      (aOR=0.39; 95% CI: 0.38-0.40), respectively). The likelihood of HPVV programme
      initiation among immigrants increased with time in Denmark ((aOR=2.28; 95% CI:
      2.11-2.48) for immigrants living in Denmark for 16-20 years compared to 6-10
      years)). CONCLUSION: The initiation of the free-of-charge HPVV programme was
      satisfactory. However, large differences in uptake were demonstrated, indicating
      that some target groups are harder to reach than others. The integration process
      (as related to use of health services) occurs over many years where differences
      between the different population groups seem to vanish.

PMID- 29074190
TI  - Molecular events leading to HPV-induced high grade neoplasia.
AB  - Cervical cancer is initiated by high-risk types of the human papillomavirus
      (hrHPV) and develops via precursor stages, called cervical intraepithelial
      neoplasia (CIN). High-grade CIN lesions are considered true precancerous lesions
      when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing
      cells. This results in abolishment of normal cell cycle control via p53 and pRb
      degradation. However, it has become clear that these viral oncogenes possess
      additional oncogenic properties, including interference with the DNA methylation
      machinery and mitotic checkpoints. Identification of the resulting molecular
      events leading to high-grade neoplasia will 1) increase our understanding of
      cervical carcinogenesis, 2) yield biomarkers for early diagnosis, and 3) identify
      therapeutic targets for HPV-induced (pre) cancerous lesions. This review will
      briefly summarise current advances in our understanding of the molecular
      alterations in the host cell genome that occur during HPV-induced carcinogenesis.

PMID- 29074188
TI  - The high-risk HPV E6 target scribble (hScrib) is required for HPV E6 expression
      in cervical tumour-derived cell lines.
AB  - The ability of high-risk HPV E6 oncoproteins to target cellular proteins which
      harbor PDZ domains is believed to play an important role in the virus life cycle
      and to influence the ability of these viruses to bring about malignant
      transformation. Whilst many of these PDZ proteins are potential tumour
      suppressors, involved in the control of cell polarity and cell-contact, recent
      studies suggest that mislocalisation or overexpression might result in the
      emergence of oncogenic functions. This has been shown most clearly for two E6
      targets, hDlg and hScrib. In this study we show that hScrib plays such a role in
      HeLa cells, where its expression is required for maintaining high levels of HPV
      18 E6 protein. Loss of hScrib has no effect on E6 stability but results in lower
      levels of E6 transcription and a reduced rate of E6 translation. We further show
      that, in the context of cervical tumour-derived cell lines, both hScrib and E6
      cooperate in the activation of the S6 kinase signaling pathway, and thereby
      contribute towards maintaining high rates of protein translation. These results
      indicate that the residual hScrib that is present within HPV transformed cells is
      pro-oncogenic, and highlights the dual functions of E6 cell polarity targets.

PMID- 29074192
TI  - IPVS Policy statement on safety of HPV vaccines.

PMID- 29074191
TI  - Prevalence, genotyping, and correlates of anogenital HPV infection in a
      population-based sample of women in Puerto Rico.
AB  - BACKGROUND: Oncogenic HPV infection is associated to anogenital cancer. We
      estimate the prevalence and correlates of anogenital HPV infection among a
      population-based sample of women aged 16-64 years living in the metropolitan area
      of Puerto Rico. METHODS: 564 women completed face-to-face and computer assisted
      interviews and self-collected anal and cervical specimens. HPV DNA testing used
      MY09/MY11 consensus HPV L1 primers and beta-globin as an internal control for
      sample amplification. Positive specimens were typed by dot-blot hybridization.
      RESULTS: Weighted prevalence of cervical, anal, and cervical/anal co-infection
      was 29.4%, 38.6%, and 17.1%, respectively. The commonest oncogenic HPV types
      detected in the cervix and anus were: 68 (8% vs. 7%) and 16 (5.5% vs. 5.1%),
      correspondingly. Having >=3 lifetime sexual partners (OR: 2.3; 95% CI: 1.5-3.5)
      and last year anal intercourse (OR: 1.6; 95% CI: 1.1-2.5) increased the odds of
      anogenital HPV infection. Cervical infection was independently associated to anal
      infection (OR: 3.0; 95% CI: 2.0-4.6). CONCLUSIONS: Similar to others, our results
      confirm the burden of anogenital HPV infection in women and its relationship with
      sexual behavior. As vaccination increases, future studies should monitor changing
      trends in HPV infection in this population, and the relationship between anal and
      cervical HPV-related disease.

PMID- 29074193
TI  - Prevalence and risk factors associated with high-grade anal squamous
      intraepithelial lesions (HSIL)-AIN2 and HSIL-AIN3 in homosexual men.
AB  - BACKGROUND: Anal intraepithelial neoplasia grade 2 (AIN2) and AIN grade 3 (AIN3)
      are commonly grouped together as high grade squamous intraepithelial lesions
      (HSIL). We assessed risk factors for HSIL-AIN2 and HSIL-AIN3 in a cohort of
      homosexual men. METHODS: At the baseline visit in the Study for the Prevention of
      Anal Cancer (SPANC), all men completed a questionnaire and underwent anal
      swabbing for cytology and HPV genotyping, followed by high resolution anoscopy.
      RESULTS: Composite-HSIL prevalence was 47% and 32% among 220 HIV-positive and 396
      HIV-negative men, respectively. HSIL-AIN3 (37.7% versus 24.7%; p<0.001), but not
      HSIL-AIN2 (9.5% versus 7.6%; p=0.395) was more common in HIV-positive men. Recent
      receptive anal partners (p-trend=0.045), and increasing number of high-risk (HR)
      HPV types (p-trend<0.001) were associated with HSIL-AIN2. Lifetime receptive
      partners (p-trend<0.001), HIV status (OR 1.74; 95% CI: 1.05-2.87) and HPV16 (OR
      3.00; 95% CI: 1.56-5.75) were associated with HSIL-AIN3. HPV16 was the most
      common HR-HPV type detected in men with HSIL-AIN3, both HIV-negative (61.1%) and
      HIV-positive (54.9%). HPV16 was less commonly detected in men with HSIL-AIN2.
      CONCLUSIONS: Grouping HSIL-AIN2 and HSIL-AIN3 as HSIL may mask considerable
      heterogeneity in anal cancer risk. Given the strong link between HPV16 and anal
      cancer, men with HSIL-AIN3 and HPV16 are likely to be at greatest risk of cancer.

PMID- 29074195
TI  - Presence of enteric viruses, bioaccumulation and stability in Anomalocardia
      brasiliana clams (Gmelin, 1791).
AB  - Bivalve mollusks are filter feeders and may accumulate human pathogens in their
      tissues. Many studies demonstrated human diseases associated with bivalve
      consumption, especially oysters. Anomalocardia brasiliana clams are distributed
      along the Brazilian coastal area and are an exotic ingredient for some typical
      dishes in Brazil. Even though there are several reports describing the
      contamination of oysters and mussels with human pathogens, there is a lack of
      studies reporting contamination of A. brasiliana with human pathogens. An
      evaluation of natural microbiological contamination in A. brasiliana samples over
      a period of 18months (November 2014 to April 2016) showed that the bacteria
      indices were in accordance with Brazilian regulations (E. coli<230MPN and
      Salmonella sp. absent in 25g of meat). However, the enteric viruses evaluated
      were detected throughout the analysis period, with the highest result for the
      hepatitis A virus (HAV); followed by Rotavirus-A (RVA); Human Adenovirus (HAdV)
      and Norovirus GI (NoV GI). The bioaccumulation of enteric viruses by A.
      brasiliana during a period of 24h was performed using NoV GI and GII, HAV, RVA
      and HAdV as models. Interestingly the mollusk demonstrated different uptake
      behaviors in relation to these viruses throughout the time period. NoV GI was the
      most adsorbed virus after 24h. HAV concentration was <1% at 3h, but it increased
      to <10% at 8h, remaining unchanged until 12h, and decreasing to <3% at 24h; HAdV
      reached its highest concentration at 12h, being released by the animals and
      lowering to <3% at 24h. RVA bioaccumulation was unstable over time, reaching its
      highest values after 24h (<5%); NoV GII bioaccumulation remained <1%. Thermal
      inactivation of HAdV-2 in A. brasiliana was also evaluated. After the usual
      gentle cooking procedure using different times (0, 1, 1.5, 3 and 5mins), viral
      infectivity was evaluated using ICC-et-RT-qPCR. The temperature inside the DT
      remained <80 degrees C over time and after 5min of cooking the HAdV reached a
      decay of 90% (1 log10). The results showed a real warn to the consumers that can
      be exposed to infectious human viruses if they eat these clams improperly cooked.
      HAV was the most detected virus in these animals, which may lead to outbreaks. A.
      brasiliana exhibited distinct behavior in NoV GI bioaccumulation and persistence,
      pointing to the need for further studies about the cellular ligands used by these
      viruses to become attached to these clams.

PMID- 29074194
TI  - Improving margin revision: Characterization of tumor bed margins in early oral
      tongue cancer.
AB  - OBJECTIVES: To improve margin revision, this study characterizes the number,
      fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2
      pN0 squamous cell carcinoma (SCC) of the oral tongue. MATERIALS AND METHODS:
      Pathology reports (n=346) were reviewed. TBM parameters were indexed. In Group 1
      patients all margins were obtained from the glossectomy specimen and there were
      no TBM. In Revision Group/Group 2 (n=103), tumor bed was sampled to revise
      suboptimal margins identified by examination of the glossectomy specimen. In
      Group 3 (n=124), TBM were obtained before examination of the glossectomy
      specimen. RESULTS AND CONCLUSIONS: Fewer TBMs were obtained per patient in Group
      2 compared to Group 3 (57/103, 55% of patients with <3 vs. 117/124, 94%, >=3
      TBMs, respectively). The new margin surface was more frequently indicated in
      Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p<.001). If
      glossectomy specimen margins are accepted as the reference standard, then the TBM
      was 15% sensitive in Group 2 (95% confidence interval [CI], 7-29) and 32%
      sensitive in Group 3 (95% CI, 15-55). TBM fragmentation (23/103, 22% vs. 42/124,
      34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were
      similar between Groups 2 and 3. The new margin surface was not indicated in 6 of
      11 cases with discrepant frozen vs. permanent pathology findings, precluding
      judgment on final margin status. To facilitate the assessment of final margins,
      TBM should be represented by one tissue fragment with a marked new margin
      surface.

PMID- 29074196
TI  - The preservation of Listeria-critical foods by a combination of endolysin and
      high hydrostatic pressure.
AB  - The aim of this work was to examine the combination of endolysin PlyP825 and high
      hydrostatic pressure (HHP) processing against a cocktail of stationary phase
      Listeria monocytogenes cells in several Listeria-critical food products (i.e.
      milk, mozzarella and smoked salmon). In order to determine the efficacy of the
      combined application, both challenge-lethality tests and storage tests were
      performed. In milk and mozzarella, we could demonstrate that the application of
      PlyP825 prior to HHP processing allowed for a synergistic inactivation of cells,
      a reduction in the pressure level with equal antimicrobial efficacy and an
      enhanced eradication of L. monocytogenes during storage at abuse temperatures.
      For smoked salmon, no such effects were detected. Although the efficacy of the
      method was highly dependent on the food vehicle and parameters applied, we hereby
      demonstrated the potential of the combined endolysin-HHP application for complete
      eradication of L. monocytogenes from foods at milder processing conditions.

PMID- 29074197
TI  - Mitochondrial dysfunction, perturbations of mitochondrial dynamics and biogenesis
      involved in endothelial injury induced by silica nanoparticles.
AB  - As silica nanoparticles (SiNPs) pervade the global economy, however, the followed
      emissions during the manufacturing, use, and disposal stages inevitably bring an
      environmental release, potentially result in harmful impacts. Endothelial
      dysfunction precedes cardiovascular disease, and is often accompanied by
      mitochondrial impairment and dysfunction. We had reported endothelial dysfunction
      induced by SiNPs, however, the related mechanisms by which SiNPs interact with
      mitochondria are not well understood. In the present study, we examined SiNPs
      induced mitochondrial dysfunction, and further demonstrated their adverse effects
      on mitochondrial dynamics and biogenesis in endothelial cells (HUVECs).
      Consequently, SiNPs entered mitochondria, caused mitochondrial swelling, cristae
      disruption and even disappearance. Further analyses revealed SiNPs increased the
      intracellular level of mitochondrial reactive oxygen species, eventually
      resulting in the collapse of mitochondrial membrane potential, impairments in ATP
      synthesis, cellular respiration and the activities of three ATP-dependent enzymes
      (including Na+/K+-ATPase, Ca2+-ATPase and Ca2+/Mg2+-ATPase), as well as an
      elevated intracellular calcium level. Furthermore, mitochondria in SiNPs-treated
      HUVECs displayed a fission phenotype. Accordingly, dysregulation of the key gene
      expressions (FIS1, DRP1, OPA1, Mfn1 and Mfn2) involved in fission/fusion event
      further certified the SiNPs-induced perturbation of mitochondrial dynamics.
      Meanwhile, SiNPs-treated HUVECs displayed declined levels of mitochondrial DNA
      copy number, PGC-1alpha, NRF1 and also TFAM, indicating an inhibition of
      mitochondrial biogenesis triggered by SiNPs via PGC-1alpha-NRF1-TFAM signaling.
      Overall, SiNPs triggered endothelial toxicity through mitochondria as target,
      including the induction of mitochondrial dysfunction, as well as the
      perturbations of their dynamics and biogenesis.

PMID- 29074198
TI  - Seasonal variations and sources of atmospheric polycyclic aromatic hydrocarbons
      and organochlorine compounds in a high-altitude city: Evidence from four-year
      observations.
AB  - Lijiang is a high-altitude city located on the eastern fringe of the Tibetan
      Plateau, with complex seasonal atmospheric circulations (i.e. westerly wind,
      Indian Monsoon, and East Asia Monsoon). Very few previous studies have focused on
      seasonal variations and sources of organic pollutants in Lijiang. In this study,
      a four-year air campaign from June 2009 to July 2013 was conducted to investigate
      the temporal trends and the sources of polycyclic aromatic hydrocarbons (PAHs)
      and organochlorine compounds [including organochlorine pesticides (OCPs) and
      polychlorinated biphenyls (PCBs)]. The atmospheric PAH concentrations in winter
      are 2-3 times of those in summer, probably because of the combined result of
      enhanced local emission and long-range atmospheric transport (LRAT) during
      winter. Traffic pollution was the primary local source of PAHs, while biomass
      burning is the dominant LRAT source. OCPs and PCBs also mainly underwent LRAT to
      reach Lijiang. The peak concentrations of most of OCPs occurred in pre-monsoon
      season and winter, which were carried by air masses from Myanmar and India
      through westerly winds. As compared with other sites of the Tibetan Plateau,
      without the direct barrier of the Himalaya, Lijiang is easily contaminated by the
      incursion of polluted air masses.

PMID- 29074200
TI  - Data management of clinical trials during an outbreak of Ebola virus disease.
AB  - INTRODUCTION: Clinical trial data management (DM) conducted during outbreaks like
      that of Ebola virus disease (EVD) in West Africa, 2014-2016, has to adapt to
      specific, unique circumstances. CTU Bern was asked to set up a safe data
      capture/management system that could be launched within a few weeks and cover two
      different vaccine trials. This article describes some of the challenges we faced
      and our solutions during the two different trials. METHODS: Setting up a DM
      system was split into four phases/tasks: (1) quick set-up of the (electronic)
      data capture system (EDC) and mobile infrastructure in Bern, (2) moving the EDC
      and infrastructure to Conakry, Guinea and implementation of a local data
      management centre (DMC), (3) running the DMC, and (4) data cleaning. The DMC had
      to meet the following criteria: (1) quick implementation, (2) efficient
      maintenance and handling of data, and (3) procedures to guarantee data quality.
      The EDC (REDCap) was setup as a local area network. In order to ensure high data
      quality, double data entry, and then review of inconsistencies and offline
      plausibility checks were implemented. RESULTS: From the start of CTU Bern's
      involvement to the productive EDC took 11 weeks. It was necessary to adapt
      processes for dealing with data continuously throughout the trial conduct phase.
      The data management team processed 171,794 case report form pages from a total of
      14,203 participants in the period between March and December 2015. CONCLUSION:
      Data management is a key task supporting trial conduct. For trials in emergency
      situations, many of our approaches are suitable, but we also provide a list of
      aspects that might be done differently.

PMID- 29074201
TI  - Safety, acceptability and tolerability of uncoated and excipient-coated high
      density silicon micro-projection array patches in human subjects.
AB  - Most vaccinations are performed by intramuscular injection with a needle and
      syringe. However, this method is not ideal due to limitations, such as the risk
      of needle-stick injury, the requirement for trained personnel to give injections
      and the need to reconstitute lyophilized vaccines. Therefore, we tested an
      alternative delivery technology that overcomes the problems with needle and
      syringe. The NanopatchTM is an array of 10,000 silicon micro-projections per cm2
      that can be dry-coated with vaccine for skin delivery. The high number and
      density of micro-projections means that high velocity application is required to
      achieve consistent skin penetration. Before clinically testing a vaccine
      Nanopatch, this study tests the safety, tolerability and acceptability/utility of
      uncoated and excipient-coated Nanopatches in healthy adults. Nanopatches were
      applied to skin of the upper arm and volar forearm and left in contact with the
      skin for two minutes before removal. The application sites were assessed for
      local skin response over 28 days. Acceptability interviews were also performed.
      No unexpected adverse events directly related to the Nanopatch application were
      reported. All applications of the Nanopatch resulted in an expected erythema
      response which faded between days 3 and 7. In some subjects, some skin
      discolouration was visible for several days or up to 3 weeks after application.
      The majority (83%) of subjects reported a preference for the Nanopatch compared
      to the needle and syringe and found the application process to be simple and
      acceptable. On a pain scale from 0 to 10, 78% of applications were scored "0" (no
      pain) with the average scores for less than 1. The results from this study
      demonstrate the feasibility of the Nanopatch to improve vaccination by showing
      that application of the product without vaccine to human skin is safe, tolerable
      and preferred to needle and syringe administration. Clinical trial registry ID:
      ACTRN1261500083549.

PMID- 29074199
TI  - Pain catastrophizing, perceived injustice, and pain intensity impair life
      satisfaction through differential patterns of physical and psychological
      disruption.
AB  - BACKGROUND AND PURPOSE: Previous research has highlighted the importance of
      cognitive appraisal processes in determining the nature and effectiveness of
      coping with chronic pain. Two of the key variables implicated in appraisal of
      pain are catastrophizing and perceived injustice, which exacerbate the severity
      of pain-related distress and increase the risk of long-term disability through
      maladaptive behavioural responses. However, to date, the influences of these
      phenomena have not been examined concurrently, nor have they been related
      specifically to quality of life measures, such as life satisfaction. METHODS:
      Using data from an online survey of 330 individuals with chronic pain, structural
      path modelling techniques were used to examine the independent effects of pain
      catastrophizing, perceived injustice, and average pain intensity on life
      satisfaction. Two potential mediators of these relationships were examined:
      depressive symptoms and pain-related interference. RESULTS: Results indicated
      that depressive symptoms fully mediated the relationship between pain
      catastrophizing and life satisfaction, and pain interference fully mediated the
      relationship between pain intensity and life satisfaction. Both depressive
      symptoms and pain interference were found to significantly mediate the
      relationship between perceived injustice and life satisfaction, but perceived
      injustice continued to demonstrate a significant and negative relationship with
      life satisfaction, above and beyond the other study variables. CONCLUSIONS: The
      current findings highlight the distinct affective and behavioural mediators of
      pain and maladaptive cognitive appraisal processes in chronic pain, and highlight
      their importance in both perceptions of pain-related interference and longer-term
      quality of life.

PMID- 29074202
TI  - Recruitment barriers for prophylactic vaccine trials: A study in Belgium.
AB  - Recruitment of volunteers is one of the main challenges in clinical trial
      management, and there is little information about recruitment barriers for
      preventative vaccine trials. We investigated both the recruitment barriers and
      recruitment strategies for preventive vaccine trials in Belgium. A 10 min survey
      was used as well as interviews of staff at all clinical trial sites in Belgium
      that regularly perform vaccine trials. We observed that there are successful
      recruitment strategies and few recruitment issues for trials involving healthy
      adults and those over 65 years old. However, challenges face the recruitment of
      paediatric populations, pregnant women, patients and the very elderly (over 85
      years old). From these results, we identified three priority areas to increase
      recruitment for prophylactic vaccine trials in Belgium. These are: the lack of
      public knowledge about infectious diseases; the lack of resources of healthcare
      professionals to take part in clinical trials; and the burden to potential
      volunteers to take part in a trial. These were discussed with stakeholders and
      solutions were proposed.

PMID- 29074203
TI  - A simply enzymatic hydrolysis pretreatment for beta-mannanase production from
      konjac powder.
AB  - Currently, the traditional fermentation using konjac powder for beta-mannanase
      production presents operational difficulties and high energy consumption, because
      of the individual hot air sterilization for konjac powder. A simply enzymatic
      hydrolysis pretreatment for konjac powder was developed to solve the problems of
      the traditional process in a 7-L fermenter. In the new process, when hydrolysis
      yield of konjac powder was above 50%, the media became liquid state from
      gelatinous state and could be sterilized immediately, avoiding the hot air
      sterilization and solving the operational difficulties. Interestingly, the new
      process didn't have negative influence on beta-mannanase production.
      Additionally, it could save close to 23% of power consumption during the whole
      fermentation. For another example, it did work well using locust bean gum for
      beta-mannanase production in a 7-L fermenter. Therefore, the new process might be
      scaled up for industrial production using mannan-based bioresource as substrate.

PMID- 29074204
TI  - Synergistic effects of metal salt and ionic liquid on the pretreatment of
      sugarcane bagasse for enhanced enzymatic hydrolysis.
AB  - High cost of ionic liquids (ILs) restricts the industrial application of IL
      mediated lignocellulose pretreatment. In this study, a simple and economic
      technology for the pretreatment of natural lignocellulose was developed. The
      delignification capacity of aqueous choline ornithine ([Cho][Orn]) and
      hemicellulose-removal capacity of metal salt FeCl2 were combined. The changes of
      morphological structure and composition indicated a synergistic interaction of
      [Cho][Orn] and FeCl2 in the pretreatment process. The delignification and
      hemicellulose-removal capacity of aqueous [Cho][Orn]50% solution was
      significantly improved in the presence of FeCl2 by 28% and 53%, respectively. The
      combination use of FeCl2 and [Cho][Orn] made it possible to save the amount of IL
      used for pretreatment in half. Enhancement effect of metal salts on the IL
      pretreatment efficiency was proved.

PMID- 29074205
TI  - Lung Cancer Awareness Month-A Lot of Progress, But More Work Needs to Be Done.

PMID- 29074206
TI  - "Quick, Where Is My Cigarette?": Mining Tobacco History for More Information on
      Risk.

PMID- 29074207
TI  - Resistance in trans-ition.

PMID- 29074208
TI  - A Case of Concurrent De Novo C797S and L858R EGFR Mutation Detected in Stage IA
      Non-Small Cell Lung Cancer Patient.

PMID- 29074209
TI  - Acquired BRAF V600E Mutation as Resistant Mechanism after Treatment with Third
      Generation EGFR Tyrosine Kinase Inhibitor.

PMID- 29074210
TI  - Nivolumab-Induced Acute Diabetes Mellitus and Hypophysitis in a Patient with
      Advanced Pulmonary Pleomorphic Carcinoma with a Prolonged Tumor Response.

PMID- 29074211
TI  - Large Cell Neuroendocrine Lung Carcinoma Transformation as an Acquired Resistance
      Mechanism to Osimertinib.

PMID- 29074212
TI  - Detection of Discrepant Driver Mutations in a Patient with Two Synchronous
      Primary Non-Small Cell Lung Cancers (NSCLCs) with Liquid Biopsy.

PMID- 29074213
TI  - Osimertinib Dose Escalation Induces Regression of Progressive EGFR T790M-Mutant
      Leptomeningeal Lung Adenocarcinoma.

PMID- 29074215
TI  - Synchronous or Metachronous Oligometastases.

PMID- 29074214
TI  - Long-Term Outcome of Surgery or Stereotactic Radiotherapy for Lung Oligo
      recurrence.

PMID- 29074216
TI  - Response to Letter to the Editor.

PMID- 29074217
TI  - Systematically assessed symptoms as outcome predictors in emergency patients.
AB  - INTRODUCTION: It is known that symptoms are predictive of mortality in
      "nonsurgical" emergency patients. It is unknown whether a prospective,
      systematic, and "unscreened" assessment of all symptoms is of any prognostic
      value. Therefore, we aimed to examine the association between symptoms and
      outcomes in an all-comer population. METHODS: Data were acquired during 6weeks at
      the ED of the University Hospital Basel, a tertiary hospital. Consecutive
      patients presenting to the ED were included. Symptoms at presentation were
      systematically assessed using a comprehensive questionnaire. RESULTS: A
      consecutive sample of 3960 emergency patients with a median age of 51years (51.7%
      male) was studied. The median number of symptoms was two. In the group of
      patients with the most prevalent symptoms, the median number of symptoms ranged
      between two and five. Overall, hospitalisation rate was 31.2%, referral to
      intensive care was 5.5%, in-hospital-mortality was 1.4%, and one-year mortality
      was 5.8%. In-hospital mortality ranged from 0% to 4.3%, and one-year mortality
      from 0% to 14.4% depending on the presenting symptoms. Dyspnoea and weakness were
      significant predictors of one-year mortality (14.4% and 9.2%, respectively).
      DISCUSSION: Most emergency patients indicated two or more symptoms.
      Systematically assessed symptoms at presentation can be used for prediction of
      outcomes. While dyspnoea is a known predictor, weakness has not been identified
      as predictor of mortality before. This knowledge could be used to improve risk
      stratification- thereby reducing the risk of adverse outcomes.

PMID- 29074218
TI  - Avasimibe: A novel hepatitis C virus inhibitor that targets the assembly of
      infectious viral particles.
AB  - Direct-acting antivirals (DAAs), which target hepatitis C virus (HCV) proteins,
      have exhibited impressive efficacy in the management of chronic hepatitis C.
      However, the concerns regarding high costs, drug resistance mutations and
      subsequent unexpected side effects still call for the development of host
      targeting agents (HTAs) that target host factors involved in the viral life cycle
      and exhibit pan-genotypic antiviral activity. Given the close relationship
      between lipid metabolism and the HCV life cycle, we investigated the anti-HCV
      activity of a series of lipid-lowering drugs that have been approved by
      government administrations or proven safety in clinical trials. Our results
      showed that avasimibe, an inhibitor of acyl coenzyme A:cholesterol
      acyltransferase (ACAT), exhibited marked pan-genotypic inhibitory activity and
      superior inhibition against HCV when combined with DAAs. Moreover, avasimibe
      significantly impaired the assembly of infectious HCV virions. Mechanistic
      studies demonstrated that avasimibe induced downregulation of microsomal
      triglyceride transfer protein expression, resulting in reduced apolipoprotein E
      and apolipoprotein B secretion. Therefore, the pan-genotypic antiviral activity
      and clinically proven safety endow avasimibe exceptional potential as a candidate
      for combination therapy with DAAs. In addition, the discovery of the antiviral
      properties of ACAT inhibitors also suggests that inhibiting the synthesis of
      cholesteryl esters might be an additional target for the therapeutic intervention
      for chronic HCV infection.

PMID- 29074221
TI  - Declining Use of Orthotopic Reconstruction Worldwide-What Went Wrong?

PMID- 29074220
TI  - Development of a multiplexed tumor-associated autoantibody-based blood test for
      the detection of colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies
      worldwide, and early diagnosis is vital to improving prognoses. We explored the
      diagnostic potential of a multiplex autoantibody panel as a biomarker for the
      detection of CRC by ELISA. METHODS: In total, 192 serum samples (92 CRC and 100
      matched controls) were tested against a panel of 12 tumor-associated antigens
      (TAAs): RPH3AL, RPL36, SLP2, p53, survivin, ANAXA4, SEC61B, CCCAP, NYCO16, NMDAR,
      PLSCR1, and HDAC5. Individual and combined autoantibody signatures were examined.
      RESULTS: Compared to individual autoantibody markers, the combinations of TAAs
      provided better discrimination between tumorous and normal sera. The overall
      sensitivity of a selected panel of four antibodies (anti-SLP2, -p53, -SEC61B, and
      -PLSCR1) was 64.1%, with a specificity of 80% that increased to 83.7% when
      carcinoembryonic antigen (CEA) measurement was added. Furthermore, the
      sensitivity of the panel of four antibodies for early and advanced stages of CRC
      was 66.7% and 62%, increasing to 88.3% and 84%, respectively, when CEA was added.
      CONCLUSIONS: We identified a panel of four antibodies as a promising diagnostic
      biomarker for the detection of CRC.

PMID- 29074219
TI  - A novel neutralizing human monoclonal antibody broadly abrogates hepatitis C
      virus infection in vitro and in vivo.
AB  - : Infections with hepatitis C virus (HCV) represent a worldwide health burden and
      a prophylactic vaccine is still not available. Liver transplantation (LT) is
      often the only option for patients with HCV-induced end-stage liver disease.
      However, immediately after transplantation, the liver graft becomes infected by
      circulating virus, resulting in accelerated progression of liver disease.
      Although the efficacy of HCV treatment using direct-acting antivirals has
      improved significantly, immune compromised LT-patients and patients with advanced
      liver disease remain difficult to treat. As an alternative approach, interfering
      with viral entry could prevent infection of the donor liver. We generated a human
      monoclonal antibody (mAb), designated 2A5, which targets the HCV envelope. The
      neutralizing activity of mAb 2A5 was assessed using multiple prototype and
      patient-derived HCV pseudoparticles (HCVpp), cell culture produced HCV (HCVcc),
      and a human-liver chimeric mouse model. Neutralization levels observed for mAb
      2A5 were generally high and mostly superior to those obtained with AP33, a well
      characterized HCV-neutralizing monoclonal antibody. Using humanized mice,
      complete protection was observed after genotype 1a and 4a HCV challenge, while
      only partial protection was achieved using gt1b and 6a isolates. Epitope mapping
      revealed that mAb 2A5 binding is conformation-dependent and identified the E2
      region spanning amino acids 434 to 446 (epitope II) as the predominant contact
      domain. CONCLUSION: mAb 2A5 shows potent anti-HCV neutralizing activity both in
      vitro and in vivo and could hence represent a valuable candidate to prevent HCV
      recurrence in LT-patients. In addition, the detailed identification of the
      neutralizing epitope can be applied for the design of prophylactic HCV vaccines.

PMID- 29074222
TI  - Tumor Volume on Biopsy of Low Risk Prostate Cancer Managed with Active
      Surveillance.
AB  - PURPOSE: Contemporary clinical guidelines recommend active surveillance of men
      with low risk prostate cancer. Low risk disease spans any potential volume of
      Gleason score 6 cancer without sufficient attention to tumor volume in the past.
      Therefore, we compared tumor characteristics in men at low risk on active
      surveillance to men treated with radical prostatectomy. MATERIALS AND METHODS: We
      evaluated an institutional cohort of 1,633 men with very low risk disease
      (clinical stage T1c, prostate specific antigen density less than 0.15 ng/ml/cm3,
      2 or more positive cores and 50% or greater core involvement) and low risk
      disease (clinical stage T2a or less, prostate specific antigen less than 10 ng/ml
      and Gleason score 6 or less). Among patients at low risk we calculated the
      proportion who failed to meet very low risk volume criteria (greater than 2
      positive cores or greater than 50% core involvement). Clinical and pathological
      metrics in the active surveillance cohort were compared to those in a cohort of
      men at low risk who underwent radical prostatectomy in the current era of 2011 to
      2016. RESULTS: In the active surveillance cohort 1,119 men (69%) met very low
      risk criteria and 514 (31%) had low risk disease. In the low risk population only
      138 men (27%) harbored higher volume cancer exceeding very low risk criteria
      compared to 815 (82%) at low risk who underwent radical prostatectomy (p <0.001).
      Overall the low risk active surveillance population had fewer positive biopsy
      cores (median 1 vs 3, p <0.001) and a lower maximum percent of core involvement
      (median 10% vs 40%, p <0.001) compared to patients at low risk who underwent
      radical prostatectomy. CONCLUSIONS: Data supporting the safety of active
      surveillance in men at low risk at our institution were derived from a distinct
      subgroup harboring a limited cancer volume. Until acceptable outcomes are
      confirmed for higher volume tumors it is important to remain mindful of these
      limitations before broadly recommending active surveillance to all low risk men.

PMID- 29074223
TI  - Is the Epworth Sleepiness Scale a useful tool for screening excessive daytime
      sleepiness in commercial drivers?
AB  - The significant social and economic impact of excessive daytime sleepiness makes
      sleep evaluation a primary medical need in commercial drivers. However, the best
      screening tool is still matter of debate. In our cohort of 221 commercial
      drivers, only ten (4.5%) had Epworth Sleepiness Scale scores indicative of
      excessive daytime sleepiness. These findings and the lack of concordance in
      estimating excessive daytime sleepiness among commercial drivers in previous
      studies using the same psychometric measure indicate that the Epworth Sleepiness
      Scale is not a reliable tool. This may be due to the low internal consistency of
      the scale in non-clinical samples and the possible intentional underscoring of
      sleepiness due to a perceived threat of driver's license suspension. Moreover,
      the reliability of the Epworth Sleepiness Scale results may be strongly
      influenced by the administration setting. The clinical application of inexpensive
      less time-consuming new tools like performance tests should be considered for the
      objective evaluation of excessive daytime sleepiness in commercial drivers.

PMID- 29074224
TI  - Phochrodines A-D, first naturally occurring new chromenopyridines from mangrove
      entophytic fungus Phomopsis sp. 33.
AB  - Four new chromenopyridine derivatives, phochrodines A-D (1-4), were identified
      from mangrove entophytic fungus Phomopsis sp. 33# by means of various modern
      chromatographic, spectroscopic and single crystal X-ray diffraction techniques.
      Compounds 1-4 with an unusual 5H-chromeno[4,3-b]pyridine skeleton were the first
      naturally occurring chromenopyridines. Their anti-inflammatory, antioxidant and
      cytotoxic activities were evaluated. 3 and 4 showed moderate inhibition of nitric
      oxide production with IC50 values of 49.0 as well as 51.0MUM, respectively. 4 had
      well ability to scavenge DPPH radical with IC50 value of 34.0MUM. The four had no
      cytotoxic activity for MDA-MB-435 breast cancer cells.

PMID- 29074225
TI  - Phenylisotertronic acids from the TCM endophytic fungus Phyllosticta sp.
AB  - Four new phenylisotertronic acids (1a/1b, 2a, and 3a) were isolated from a TCM
      endophytic fungal strain Phyllosticta sp. J13-2-12Y obtained from the leaves of
      Acorus tatarinowii, along with two known ones (2b and 3b). Compounds 1-3 all
      existed as mixtures of enantiomers, and their corresponding optically pure
      enantiomers were successfully isolated by chiral HPLC. The structures of isolated
      compounds were determined by comprehensive spectroscopic analyses and X-ray
      diffraction. Their absolute configurations were determined by ECD experiments and
      quantum chemical calculations. In addition, the antimicrobial activities and the
      cytotoxicities of these three pairs of optically pure enantiomers (1a/1b, 2a/2b,
      and 3a/3b) had been evaluated.

PMID- 29074226
TI  - Monoterpenoid indole alkaloids from the leaves of Alstonia scholaris and their NF
      kappaB inhibitory activity.
AB  - Four new monoterpenoid indole alkaloids (MIAs), scholarisines P-S (1-4), and 14
      known MIAs (5-18) were isolated from the leaves of Alstonia scholaris (L) R. Br.
      (Apocynaceae). Their structures were elucidated by analyzing their HRESIMS data
      and NMR spectroscopic data. All of the isolated MIAs were evaluated for their
      Nuclear Factor-kappa B (NF-kappaB) inhibitory activity in HepG2-NF-kappaB-Luc
      cells. Among them, five compounds (4, 7, 8, 13 and 16) exhibited significant NF
      kappaB inhibitory activity.

PMID- 29074227
TI  - Isobenzofuranones from the aerial parts of Leontopodium leontopodioides (Wild.)
      Beauv.
AB  - A phytochemical investigation to obtain new triglyceride (TG) accumulation
      inhibitors resulted in the isolation of six new isobenzofuranones, leontopodiols
      A (1), B (2), leontopodiosides C (3), D (4), E (5), F (6), together with three
      known ones (7-9) from the aerial parts of Leontopodium leontopodioides (Willd.)
      Beauv. The structures of these isolates were identified by routine NMR
      experiments, optical rotation determination, electronic circular dichroism (ECD)
      calculation, along with chemical reaction. Moreover, compounds 1, 2, 5, and 7-9
      displayed TG accumulation inhibitory effects on HepG2 cells.

PMID- 29074228
TI  - DNA replication stress drives fragile site instability.
AB  - DNA replication stress is one of the early drivers enabling the ongoing
      acquisition of genetic changes arising during tumorigenesis. As such, it is a
      feature of most pre-malignant and malignant cells. In this review article, we
      focus on the early events initiating DNA replication stress and the preferential
      sensitivity of common fragile sites (CFSs) to this stress. CFSs are specific
      genomic regions within the normal chromosomal structure, which appear as gaps and
      breaks in the metaphase chromosomes of cells grown under mild replication stress
      conditions. The main characteristics predisposing CFSs to instability include
      late replication timing, delayed replication completion, failure to activate
      additional origins, origin paucity along large genomic regions, collision between
      replication and transcription complexes along large genes, and the presence of AT
      dinucleotide rich sequences. The contribution of these features to instability at
      CFSs during early cancer development is discussed.

PMID- 29074229
TI  - WITHDRAWN: Titanium dioxide nanoparticles induce human eosinophil adhesion onto
      endothelial EA.hy926 cells via activation of phosphoinositide 3-kinase/Akt cell
      signalling pathway.
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/about/our
      business/policies/article-withdrawal.

PMID- 29074230
TI  - A novel Differential Susceptibility framework for the study of nightmares:
      Evidence for trait sensory processing sensitivity.
AB  - Research on nightmares has largely focused on the nightmare itself and its
      associated negative consequences, framing nightmare sufferers as victims of a
      diathesis-stress induced form of psychopathology. However, there is evidence that
      frequent nightmare recallers are sensitive to a wide range of sensory and
      emotional experiences, and report vivid, bizarre and even intensely positive
      dream and daydream experiences. We propose sensory processing sensitivity as a
      novel trait marker that underlies the unique symptoms and imaginative richness
      found in nightmare-prone individuals. Sensory processing sensitivity describes an
      increased emotional reactivity, greater depth of processing, and subtle awareness
      of environmental stimuli-it is a 'for better and for worse' trait that is
      associated with positive outcomes in conditions of support, but also confers a
      tendency to be easily overwhelmed by stressors and adversity. This novel approach
      places nightmare-prone individuals within the broader framework of Differential
      Susceptibility and raises the possibility that they may benefit especially from
      supportive environments-a possibility that is particularly relevant for
      developing future treatment approaches.

PMID- 29074232
TI  - Class VIIIb APETALA2 Ethylene Response Factors in Plant Development.
AB  - The APETALA2 (AP2) transcription factor superfamily in many plant species is
      extremely large. In addition to well-documented roles in stress responses, some
      AP2 members in arabidopsis, such as those of subgroup VIIIb, which includes
      DORNROSCHEN, DORNROSCHEN-LIKE, PUCHI, and LEAFY PETIOLE, are also important
      developmental regulators throughout the plant life cycle. Information is
      accumulating from orthologs of these proteins in important crop species that they
      influence key agronomic traits, such as the release of bud-burst in woody
      perennials and floral meristem identity and branching in cereals, and thereby
      represent potential for agronomic improvement. Given the increasing recognition
      of their developmental significance, this review highlights the function of these
      proteins and addresses their phylogenetic and evolutionary relationships.

PMID- 29074231
TI  - The ENGAGE study: Integrating neuroimaging, virtual reality and smartphone
      sensing to understand self-regulation for managing depression and obesity in a
      precision medicine model.
AB  - Precision medicine models for personalizing achieving sustained behavior change
      are largely outside of current clinical practice. Yet, changing self-regulatory
      behaviors is fundamental to the self-management of complex lifestyle-related
      chronic conditions such as depression and obesity - two top contributors to the
      global burden of disease and disability. To optimize treatments and address these
      burdens, behavior change and self-regulation must be better understood in
      relation to their neurobiological underpinnings. Here, we present the conceptual
      framework and protocol for a novel study, "Engaging self-regulation targets to
      understand the mechanisms of behavior change and improve mood and weight outcomes
      (ENGAGE)". The ENGAGE study integrates neuroscience with behavioral science to
      better understand the self-regulation related mechanisms of behavior change for
      improving mood and weight outcomes among adults with comorbid depression and
      obesity. We collect assays of three self-regulation targets (emotion, cognition,
      and self-reflection) in multiple settings: neuroimaging and behavioral lab-based
      measures, virtual reality, and passive smartphone sampling. By connecting human
      neuroscience and behavioral science in this manner within the ENGAGE study, we
      develop a prototype for elucidating the underlying self-regulation mechanisms of
      behavior change outcomes and their application in optimizing intervention
      strategies for multiple chronic diseases.

PMID- 29074233
TI  - Alternative Splicing Control of Abiotic Stress Responses.
AB  - Alternative splicing, which generates multiple transcripts from the same gene, is
      an important modulator of gene expression that can increase proteome diversity
      and regulate mRNA levels. In plants, this post-transcriptional mechanism is
      markedly induced in response to environmental stress, and recent studies have
      identified alternative splicing events that allow rapid adjustment of the
      abundance and function of key stress-response components. In agreement, plant
      mutants defective in splicing factors are severely impaired in their response to
      abiotic stress. Notably, mounting evidence indicates that alternative splicing
      regulates stress responses largely by targeting the abscisic acid (ABA) pathway.
      We review here current understanding of post-transcriptional control of plant
      stress tolerance via alternative splicing and discuss research challenges for the
      near future.

PMID- 29074234
TI  - Development of a rapid and quantitative method for the analysis of viral entry
      and release using a NanoLuc luciferase complementation assay.
AB  - Subviral particles (SVPs) self-assemble and are released from cells transfected
      with expression plasmids encoding flavivirus structural proteins. Flavivirus-like
      particles (VLPs), consisting of flavivirus structural proteins and a subgenomic
      replicon, can enter cells and cause single-round infections. Neither SVPs or VLPs
      possess complete viral RNA genomes, therefore are replication-incompetent
      systems; however, they retain the capacity to fuse and bud from target cells and
      follow the same maturation process as whole virions. SVPs and VLPs have been
      previously employed in studies analyzing entry and release steps of viral life
      cycles. In this study, we have developed quantitative methods for the detection
      of cellular entry and release of SVPs and VLPs by applying a luciferase
      complementation assay based on the high affinity interaction between the split
      NanoLuc luciferase protein, LgBiT and the small peptide, HiBiT. We introduced
      HiBiT into the structural protein of West Nile virus and generated SVPs and VLPs
      harboring HiBiT (SVP-HiBiT and VLP-HiBiT, respectively). As SVP-HiBiT emitted
      strong luminescence upon exposure to LgBiT and its substrate, the nascently
      budded SVP-HiBiT in the supernatant was readily quantified by luminometry.
      Similarly, the cellular entry of VLP-HiBiT generated luminescence when VLP-HiBiT
      was infected into LgBiT-expressing cells. These methods utilizing SVP-HiBiT and
      VLP-HiBiT will facilitate research into life cycles of flaviviruses, including
      WNV.

PMID- 29074235
TI  - Transformation of roxarsone in the anoxic-oxic process when treating the
      livestock wastewater.
AB  - In order to evaluate the influence of roxarsone (ROX) on the livestock wastewater
      treatment, a lab-scale pilot employing an anoxic-oxic (A-O) process was
      investigated by adding different concentrations of ROX at different periods. The
      mass balance of arsenic (As) in the A-O system was established through the
      analysis of As speciation and As migration in the gas, liquid and solid phases.
      The results showed that around 80% of total ROX (initial concentration was
      50mgROXL-1) was eliminated in the anoxic reactor (R1) in which at least about 11%
      of total ROX was transformed to inorganic Asv (iAsv) due to the direct breaking
      of the C-As bond of ROX. Inorganic AsIII (iAsIII) and arsine (AsH3) were produced
      in R1, while the generated iAsIII in the effluent of R1 was almost completely
      oxidized to iAsV in the aerobic reactor (R2). However, the concentration of ROX
      in the effluent of R2 was almost the same as that in the effluent of R1. After
      85days operation, iAsV and residual ROX as the main forms of As were observed
      after the A-O process. Furthermore, the mass balance of As at steady state
      revealed that around 0.08%, 3.91% and 96.01% of total As was transformed into gas
      (biogas), solid (excess sludge) and liquid (effluent). Additionally, the 16S rRNA
      analysis demonstrated that the existence of ROX in livestock wastewater may play
      a crucial role in the diversity of bacterial community in the A-O system.

PMID- 29074236
TI  - Sedimentary record of antibiotic accumulation in Minnesota Lakes.
AB  - The widespread detection of antibiotics in the environment is concerning because
      antibiotics are designed to be effective at small doses. The objective of this
      work was to quantify the accumulation rates of antibiotics used by humans and
      animals, spanning several major antibiotic classes (sulfonamides, tetracyclines,
      fluoroquinolones, and macrolides), in Minnesota lake-sediment cores. Our goal was
      to determine temporal trends, the major anthropogenic source to these lacustrine
      systems, and the importance of natural production. A historical record of usage
      trends for ten human and/or animal-use antibiotics (four sulfonamides, three
      fluoroquinolones, one macrolide, trimethoprim, and lincomycin) was faithfully
      captured in the sediment cores. Nine other antibiotics were not detected.
      Ofloxacin, trimethoprim, sulfapyridine, and sulfamethazine were detected in all
      of the anthropogenically-impacted studied lakes. Maximum sediment fluxes reached
      20.5ngcm-2yr-1 (concentration 66.1ng/g) for ofloxacin, 1.2ngcm-2yr-1 (1.2ng/g)
      for trimethoprim, 3.3ngcm-2yr-1 (11.3ng/g) for sulfapyridine, and 1.0ngcm-2yr-1
      (1.6ng/g) for sulfamethazine, respectively. Natural production of lincomycin may
      have occurred in one lake at fluxes ranging from 0.4 to 1.8ngcm-2yr-1 (0.1 to
      5.8ng/g). Wastewater effluent appears to be the primary source of antibiotics in
      the studied lakes, with lesser inputs from agricultural activities.

PMID- 29074238
TI  - Dynamics of soil carbon and nitrogen stocks after afforestation in arid and semi
      arid regions: A meta-analysis.
AB  - Arid and semi-arid regions store approximately 27% of global soil organic carbon
      (SOC), thus playing an important role in the global carbon cycle. Although
      afforestation is widely used to achieve the goals of landscape protection and
      ecological restoration in these regions, its effects on the dynamics of SOC and
      total nitrogen (TN) stocks as well as the related controlling factors are still
      poorly understood. In this study, a meta-analysis was conducted by compiling
      results from published studies to evaluate the influences of afforestation on
      dynamics of SOC and TN stocks in mineral soils (0-30cm) in arid and semi-arid
      regions, and to examine whether the changes in SOC and TN stocks were influenced
      by prior land-use, planted tree species and plantation age. The results showed
      that overall, afforestation significantly increased SOC stock by 131% and TN
      stock by 88%. Prior land-use was found to be the most important factor that
      influenced the dynamics of SOC and TN stocks following afforestation.
      Significantly larger increases in SOC and TN stocks were observed after barren
      land afforestation in comparison to cropland and grassland afforestation. The
      accumulations in SOC and TN stocks after afforestation decreased in the following
      order: broadleaf deciduous forests>coniferous forests>broadleaf evergreen
      forests. However, significant differences in SOC and TN accumulations were only
      detected between broadleaf deciduous forests and broadleaf evergreen forests.
      Plantation age did not affect the dynamics of SOC and TN stocks after
      afforestation, mainly due to the rapid accumulations in SOC and TN after barren
      land afforestation. The results indicate that afforestation, especially on barren
      land with broadleaf deciduous species, provides substantial opportunities for SOC
      and TN sequestrations in arid and semi-arid regions.

PMID- 29074237
TI  - Isotopic composition of nitrogen species in groundwater under agricultural areas:
      A review.
AB  - This work reviews applications of stable isotope analysis to the studies of
      transport and transformation of N species in groundwater under agricultural
      areas. It summarizes evidence regarding factors affecting the isotopic
      composition of NO3-, NH4+ and N2O in subsurface, and discusses the use of 11B,
      18O, 13C, 34S, 87Sr/86Sr isotopes to support the analysis of delta15N values. The
      isotopic composition of NO3-, NH4+ and N2O varies depending on their sources and
      dynamics of N cycle processes. The reported delta15N-NO3- values for sources of
      NO3- are: soil organic N - +30/00-+80/00, mineral fertilizers - -80/00-+70/00;
      manure/household waste - +50/00 to +350/00. For NH4+ sources, the isotopic
      signature ranges are: organic matter - +2.4-+4.10/00, rainwater - -13.4-+2.30/00,
      mineral fertilizers - -7.4-+5.10/00, household waste - +5-+90/00; animal manure -
      +8-+110/00. For N2O, isotopic composition depends on isotopic signatures of
      substrate pools and reaction rates. delta15N values of NO3- are influenced by
      fractionation effects occurring during denitrification (E=5-400/00),
      nitrification (E=5-350/00) and DNRA (E not reported). The isotopic signature of
      NH4+ is also affected by nitrification and DNRA as well as mineralization
      (E=10/00), sorption (E=1-80/00), anammox (E=4.3-7.40/00) and volatilization
      (E=250/00). As for the N2O, production of N2O leads to its depletion in 15N,
      whereas consumption - to enrichment in 15N. The magnitude of fractionation
      effects occurring during the considered processes depends on temperature, pH, DO,
      C/NO3- ratio, size of the substrate pool, availability of electron donors, water
      content in subsoil, residence time, land use, hydrogeology. While previous
      studies have accumulated rich data on isotopic composition of NO3- in
      groundwater, evidence remains scarce in the cases of NH4+ and N2O. Further
      research is required to consider variability of delta15N-NH4+ and delta15N-N2O in
      groundwater across agricultural ecosystems.

PMID- 29074239
TI  - Flood susceptibility assessment in Hengfeng area coupling adaptive neuro-fuzzy
      inference system with genetic algorithm and differential evolution.
AB  - Floods are among Earth's most common natural hazards, and they cause major
      economic losses and seriously affect peoples' lives and health. This paper
      addresses the development of a flood susceptibility assessment that uses
      intelligent techniques and GIS. An adaptive neuro-fuzzy inference system (ANFIS)
      was coupled with a genetic algorithm and differential evolution for flood spatial
      modelling. The model considers thirteen hydrologic, morphologic and lithologic
      parameters for the flood susceptibility assessment, and Hengfeng County in China
      was chosen for the application of the model due to data availability and the 195
      total flood events. The flood locations were randomly divided into two subsets,
      namely, training (70% of the total) and testing (30%). The Step-wise Weight
      Assessment Ratio Analysis (SWARA) approach was used to assess the relation
      between the floods and influencing parameters. Subsequently, two data mining
      techniques were combined with the ANFIS model, including the ANFIS-Genetic
      Algorithm and the ANFIS-Differential Evolution, to be used for flood spatial
      modelling and zonation. The flood susceptibility maps were produced, and their
      robustness was checked using the Receiver Operating Characteristic (ROC) curve.
      The results showed that the area under the curve (AUC) for all models was >0.80.
      The highest AUC value was for the ANFIS-DE model (0.852), followed by ANFIS-GA
      (0.849). According to the RMSE and MSE methods, the ANFIS-DE hybrid model is more
      suitable for flood susceptibility mapping in the study area. The proposed method
      is adaptable and can easily be applied in other sites for flood management and
      prevention.

PMID- 29074240
TI  - Biomonitoring of intermittent rivers and ephemeral streams in Europe: Current
      practice and priorities to enhance ecological status assessments.
AB  - Intermittent rivers and ephemeral streams (IRES) are common across Europe and
      dominate some Mediterranean river networks. In all climate zones, IRES support
      high biodiversity and provide ecosystem services. As dynamic ecosystems that
      transition between flowing, pool, and dry states, IRES are typically poorly
      represented in biomonitoring programmes implemented to characterize EU Water
      Framework Directive ecological status. We report the results of a survey
      completed by representatives from 20 European countries to identify current
      challenges to IRES status assessment, examples of best practice, and priorities
      for future research. We identify five major barriers to effective ecological
      status classification in IRES: 1. the exclusion of IRES from Water Framework
      Directive biomonitoring based on their small catchment size; 2. the lack of river
      typologies that distinguish between contrasting IRES; 3. difficulties in defining
      the 'reference conditions' that represent unimpacted dynamic ecosystems; 4.
      classification of IRES ecological status based on lotic communities sampled using
      methods developed for perennial rivers; and 5. a reliance on taxonomic
      characterization of local communities. Despite these challenges, we recognize
      examples of innovative practice that can inform modification of current
      biomonitoring activity to promote effective IRES status classification.
      Priorities for future research include reconceptualization of the reference
      condition approach to accommodate spatiotemporal fluctuations in community
      composition, and modification of indices of ecosystem health to recognize both
      taxon-specific sensitivities to intermittence and dispersal abilities, within a
      landscape context.

PMID- 29074241
TI  - Bioprocessing for elimination antibiotics and hormones from swine wastewater.
AB  - Antibiotics and hormones in swine wastewater have become a critical concern
      worldwide due to the severe threats to human health and the eco-environment.
      Removal of most detectable antibiotics and hormones, such as sulfonamides (SAs),
      SMs, tetracyclines (TCs), macrolides, and estrogenic hormones from swine
      wastewater utilizing various biological processes were summarized and compared.
      In biological processes, biosorption and biodegradation are the two major removal
      mechanisms for antibiotics and hormones. The residuals in treated effluents and
      sludge of conventional activated sludge and anaerobic digestion processes can
      still pose risks to the surrounding environment, and the anaerobic processes'
      removal efficiencies were inferior to those of aerobic processes. In contrast,
      membrane bioreactors (MBRs), constructed wetlands (CWs) and modified processes
      performed better because of their higher biodegradation of toxicants. Process
      modification on activated sludge, anaerobic digestion and conventional MBRs could
      also enhance the performance (e.g. removing up to 98% SMs, 88.9% TCs, and 99.6%
      hormones from wastewater). The hybrid process combining MBRs with biological or
      physical technology also led to better removal efficiency. As such, modified
      conventional biological processes, advanced biological technologies and MBR
      hybrid systems are considered as a promising technology for removing toxicants
      from swine wastewater.

PMID- 29074242
TI  - Levels, sources and probabilistic health risks of polycyclic aromatic
      hydrocarbons in the agricultural soils from sites neighboring suburban industries
      in Shanghai.
AB  - The levels, sources and quantitative probabilistic health risks for polycyclic
      aromatic hydrocarbons (PAHs) in agricultural soils in the vicinity of power,
      steel and petrochemical plants in the suburbs of Shanghai are discussed. The
      total concentration of 16 PAHs in the soils ranges from 223 to 8214ng g-1. The
      sources of PAHs were analyzed by both isomeric ratios and a principal component
      analysis-multiple linear regression method. The results indicate that PAHs mainly
      originated from the incomplete combustion of coal and oil. The probabilistic risk
      assessments for both carcinogenic and non-carcinogenic risks posed by PAHs in
      soils with adult farmers as concerned receptors were quantitatively calculated by
      Monte Carlo simulation. The estimated total carcinogenic risks (TCR) for the
      agricultural soils has a 45% possibility of exceeding the acceptable threshold
      value (10-6), indicating potential adverse health effects. However, all non
      carcinogenic risks are below the threshold value. Oral intake is the dominant
      exposure pathway, accounting for 77.7% of TCR, while inhalation intake is
      negligible. The three PAHs with the highest contribution for TCR are BaP
      (64.35%), DBA (17.56%) and InP (9.06%). Sensitivity analyses indicate that
      exposure frequency has the greatest impact on the total risk uncertainty,
      followed by the exposure dose through oral intake and exposure duration. These
      results indicate that it is essential to manage the health risks of PAH
      contaminated agricultural soils in the vicinity of typical industries in
      megacities.

PMID- 29074244
TI  - Contributions of Kansas rangeland burning to ambient O3: Analysis of data from
      2001 to 2016.
AB  - Prescribed range/pasture burning is a common practice in Kansas to enhance the
      nutritional value of native grasses and control invading weeds, trees, and brush.
      A major concern associated with the burning is the contribution of smoke to
      elevated ground level ambient ozone (O3). The objective of this study is to
      estimate contributions of Kansas rangeland burning to ambient O3 mixing ratios
      through regression analysis (1) between observed O3 data and available satellite
      burn activity data from 2001 to 2016; and (2) between observed O3 data and the
      smoke contributions to PM2.5 which were resolved from receptor modeling. Positive
      correlations were observed between ambient O3 levels and the acres burned each
      year estimated from satellite imagery. When burned acres in April were larger
      than or equal to 1.9 million, O3>70ppb occurred at least at one of the ten
      monitoring sites in Kansas. Statistical regression models of daily maximum 8-hour
      O3 mixing ratios were developed at each of the ten monitoring sites using
      meteorological predictors. The O3 model residuals that were not explained by the
      meteorological effect models were affected by PM2.5 contributors including
      sulfate/industrial sources and emissions that generated secondary organic
      particles, such as rangeland burning, which were derived from receptor modeling.
      The average O3 model residual on the high O3 days in April was 21+/-9ppb, which
      was likely associated with smoke emissions from burning. Research will continue
      to obtain daily satellite burn activity data and to correlate burn data with
      daily O3 data, so that modeling of O3 levels can be improved under influences of
      daily burn activities. Less frequency of high O3 days was observed in April since
      2011, which may be partly due to implementation of the Flint Hills Smoke
      Management Plan which promoted better timing of burns.

PMID- 29074243
TI  - Assessing the environmental quality of sediments from Split coastal area
      (Croatia) with a battery of cell-based bioassays.
AB  - A battery of cell-based bioassays, including PLHC-1 cells, zebrafish-Pxr
      transfected COS-7 cells and estrogen receptor-recombinant yeast assay (ER-RYA),
      were applied to detect the presence of bioactive pollutants in sediments
      collected from Kastela Bay and Brac Channel (Croatia). Exposure of PLHC-1 cells
      to the sediment extracts evidenced significant cytotoxicity and presence of CYP1A
      inducers in sediments collected in Kastela Bay, near the industrial zone and
      cargo port of Split. Sediments from this area, which is highly contaminated with
      PCBs, HCB, DDTs and gamma-HCH, also activated the zebrafish Pxr (zfPxr) reporter
      system. No evidence of estrogenicity was detected for any of the sediments
      extracts in the ER-RYA assay. Importantly, the battery of in vitro assays
      identified Kastela Bay as the area with the higher anthropogenic impact, where
      sediment-bound pollutants could pose a risk to aquatic organisms. In contrast,
      sediments from the Brac Channel showed rather low response in the different
      bioassays.

PMID- 29074245
TI  - Analysis of major pollutants and physico-chemical characteristics of PM2.5 at an
      urban site in Rome.
AB  - Air quality data from a one year study at an urban roadside location in Rome are
      reported for major pollutants. Continuous concentration data of carbon monoxide,
      ozone, nitrogen dioxide, aromatic hydrocarbons and natural radioactivity were
      measured in the urban air of Rome from January 2016 to January 2017. Moreover,
      PM2.5 mass concentration and physico-chemical characteristics of single
      constituent particles are herein reported. Gaseous pollutants, except ozone, and
      PM2.5 showed maximum concentrations in December due to high atmospheric
      stability. O3 and NO2 trend analysis showed photochemical smog episodes in June
      and September. In September, during a photochemical smog episode the aromatic
      hydrocarbons contribution to ozone formation was experimentally proven. Pearson's
      coefficient among aromatic hydrocarbons and the ratio Toluene/Benzene (T/B)
      showed that pollutants were under the influence of vehicular traffic. Physico
      chemical characterization of PM2.5 single particles, carried out by field
      emission scanning electron microscope combined with energy dispersive X-ray
      spectroscopy, displayed the presence of particle diversity from natural and
      anthropogenic origin. Four principal components in the PM2.5 were identified:
      carbonaceous particles, Ca-sulphates, soil dust and building structure particles,
      metal particles. The principal source of carbonaceous particles in this urban
      area consists of the motor vehicle exhausts and the heating systems in winter.
      Traces of S and sometimes S, Na, K were detected on varying percentages of
      carbonaceous particles. These data suggested that the carbonaceous particles act
      as vehicles for strong acids, prevalently H2SO4 and alkaline metal sulphates. A
      Saharan dust contribution to PM2.5 was found in different periods. Metal
      particles included iron oxide particles, metals oxide particles and Fe-rich metal
      compounds. The identification of chemical composition of individual particles
      provide useful information to determine their origin and formation processes.

PMID- 29074246
TI  - Simulated bioavailability of phosphorus from aquatic macrophytes and
      phytoplankton by aqueous suspension and incubation with alkaline phosphatase.
AB  - Bioavailability of phosphorus (P) in biomass of aquatic macrophytes and
      phytoplankton and its possible relationship with eutrophication were explored by
      evaluation of forms and quantities of P in aqueous extracts of dried macrophytes.
      Specifically, effects of hydrolysis of organically-bound P by the enzyme alkaline
      phosphatase were studied by use of solution 31P-nuclear magnetic resonance (NMR)
      spectroscopy. Laboratory suspensions and incubations with enzymes were used to
      simulate natural releases of P from plant debris. Three aquatic macrophytes and
      three phytoplankters were collected from Tai Lake, China, for use in this
      simulation study. The trend of hydrolysis of organic P (Po) by alkaline
      phosphatase was similar for aquatic macrophytes and phytoplankton. Most monoester
      P (15.3% of total dissolved P) and pyrophosphate (1.8%) and polyphosphate (0.4%)
      and DNA (3.2%) were transformed into orthophosphate (14.3%). The major forms of
      monoester P were glycerophosphate (8.8%), nucleotide (2.5%), phytate (0.4%) and
      other monoesters P (3.6%). Proportions of Po including condensed P hydrolyzed in
      phytoplankton and aquatic macrophytes were different, with the percentage of
      22.6% and 6.0%, respectively. Proportion of Po hydrolyzed in debris from
      phytoplankton was approximately four times greater than that of Po from aquatic
      macrophytes, and could be approximately twenty-five times greater than that of Po
      in sediments. Thus, release and hydrolysis of Po, derived from phytoplankton
      debris would be an important and fast way to provide bioavailable P to support
      cyanobacterial blooming in eutrophic lakes.

PMID- 29074247
TI  - Climatic and dam-induced impacts on river water temperature: Assessment and
      management implications.
AB  - In a changing climate with a warming trend in air temperature, river water
      temperature increases as a result of heat exchange with the atmosphere. Moreover,
      of the different types of anthropogenic activity impacting rivers, the
      construction of dams appears to have multi-dimensional effects on the river
      environment, and it especially affects the thermal condition of rivers. The aim
      of the study is to identify and assess the impact of these two distinct sources
      of water temperature distortion in relation to the natural thermal conditions of
      rivers. In the study, linear trend analysis and a complex wavelet transform are
      used. The analysis focuses on daily river water temperature data for time periods
      before and after the construction of selected reservoirs in the Polish
      Carpathians, and on daily air temperature data for neighboring meteorological
      stations. Three rivers were selected for analysis: (1) Dunajec River, 22km
      downstream of the Czorsztyn-Sromowce Wyzne reservoir complex, (2) Ropa River,
      16km downstream of the Klimkowka Reservoir, and (3) Wislok River, 33km downstream
      of the Besko Reservoir. Research has shown that the significant increasing trends
      identified for water temperature are weaker than analogous trends in air
      temperature. The Czorsztyn-Sromowce Wyzne and Klimkowka reservoirs appear to
      exert considerable influence on natural air-water temperature synchronization,
      because the phase difference increases 5-fold in comparison with conditions prior
      to the construction of the reservoirs. The weakening of the natural air-water
      temperature synchrony implies diminished impact of air temperature on stream
      water temperature. However, this creates an opportunity for preparing appropriate
      management practices mitigating an increasing temperature trend in order to shape
      more favorable (natural) thermal conditions for native aquatic biota in impounded
      rivers.

PMID- 29074248
TI  - Effects of metal ions and pH on ofloxacin sorption to cassava residue-derived
      biochar.
AB  - In this study, the impacts of various cations, cation strength and pH on
      ofloxacin (OFL) adsorption to cassava residue-derived biochars were determined.
      The associated adsorption mechanisms are discussed. The biochars were prepared at
      pyrolysis temperatures ranging from 350 degrees C to 750 degrees C, and labeled
      as CW350, CW450, CW550, CW650 and CW750. The Freundlich model provided the best
      fit to describe the adsorption capacity of OFL and the Freundlich coefficient
      (logKf) increased with increasing pyrolysis temperature. The inclusion of Zn2+ or
      Al3+ increased OFL sorption capacities of five biochars, while Cu2+ reduced
      sorption to CW450 and CW550. No significant impacts on OFL sorption were observed
      in the presence of K+ and Ca2+. The concentration of Ca2+ affected the adsorption
      capacity of CW550, but had no significant impact on other biochars. The pH of OFL
      solution, ranging from 3 to 9, had no significant changes on OFL adsorption by
      all the tested biochars. Results of FTIR spectra and zeta potential indicated
      that electrostatic interactions, cationic exchange, metal bridging and micropore
      filling could be the main sorption mechanism between OFL and biochars. These
      studies indicated that cassava residue can be converted into biochars that are
      effective adsorbents for removing OFL from aqueous solution.

PMID- 29074249
TI  - Identifying non-reference sites to guide stream restoration and long-term
      monitoring.
AB  - The reference condition paradigm has served as the standard for assessing the
      outcomes of restoration projects, particularly their success in meeting project
      objectives. One limitation of relying solely on the reference condition in
      designing and monitoring restoration projects is that reference conditions do not
      necessarily elucidate impairments to effective restoration, especially diagnosing
      the causal mechanisms behind unsuccessful outcomes. We provide a spatial
      framework to select both reference and non-reference streams to guide restoration
      planning and long-term monitoring through reliance on anthropogenically altered
      ecosystems to understand processes that govern ecosystem biophysical properties
      and ecosystem responses to restoration practices. We then applied the spatial
      framework to East Fork Poplar Creek (EFPC), Tennessee (USA), a system receiving
      30years of remediation and pollution abatement actions from industrialization,
      pollution, and urbanization. Out of >13,000 stream reaches, we identified
      anywhere from 4 to 48 reaches, depending on the scenario, that could be used in
      restoration planning and monitoring for specific sites. Preliminary comparison of
      fish species composition at these sites compared to EFPC sites were used to
      identify potential mechanisms limiting the ecological recovery following
      remediation. We suggest that understanding the relative role of anthropogenic
      pressures in governing ecosystem responses is required to successful, process
      driven restoration.

PMID- 29074251
TI  - Temporal Bias: Time-Encoded Dynamic GPCR Signaling.
AB  - Evidence suggests that cells can time-encode signals for secure transport and
      perception of information, and it appears that this dynamic signaling is a common
      principle of nature to code information in time. G-protein-coupled receptor
      (GPCR) signaling networks are no exception as their composition and signal
      transduction appear temporally flexible. In this review, we discuss the potential
      mechanisms by which GPCRs code biological information in time to create 'temporal
      bias.' We highlight dynamic signaling patterns from the second messenger to the
      receptor-ligand level and shed light on the dynamics of G-protein cycles, the
      kinetics of ligand-receptor interaction, and the occurrence of distinct signaling
      waves within the cell. A dynamic feature such as temporal bias adds to the
      complexity of GPCR signaling bias and gives rise to the question whether this
      trait could be exploited to gain control over time-encoded cell physiology.

PMID- 29074250
TI  - ESC-derived thymic epithelial cells expressing MOG prevents EAE by central and
      peripheral tolerance mechanisms.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple
      sclerosis (MS), and is induced by immunization with disease-causative self
      antigens such as myelin oligodendrocyte glycoprotein (MOG). We have previously
      reported that transplantation of MOG expressing thymic epithelial progenitors
      (TEPs) derived from 129S6SvEv Tac mouse embryonic stem cells (mESCs) prevented
      the development of EAE. In this study, we expand our previous studies to show
      that transplantation of MOG expressing mESC-TEPs derived from C57BL/6 mice also
      prevents EAE development. Furthermore, by using a MOG-specific T cell receptor
      (TCR) transgenic mouse model, we demonstrate that both central and peripheral
      tolerances are involved in the prevention of EAE induced by MOG expressing mESC
      TEPs. Our results suggest that transplantation of human ESC-TEPs expressing MOG
      may provide an effective approach for the induction of MOG-specific immune
      tolerance, thereby the prevention and treatment of MS.

PMID- 29074252
TI  - Identifying past petroleum exploration related drill cutting releases and
      influences on the marine environment and benthic foraminiferal communities,
      Goliat Field, SW Barents Sea, Norway.
AB  - The present multiproxy investigation of marine sediment cores aims at: 1)
      Identifying dispersion of petroleum exploration related drill cutting releases
      within the Goliat Field, Barents Sea in 2006/07 and 2) Assessing past and present
      influence of drill cuttings on the marine environment. The cores were recovered
      5, 30, 60, 125 and 250m from the drill site in the eastward downstream direction.
      Downstream dispersion of drill cuttings is evaluated by examining sediment grain
      size distribution and barium (Ba), heavy metal, total organic carbon and sulphur
      concentrations. Dispersion of drill cuttings was limited to <125m east from the
      drill site. Influence of drill cutting releases on the marine environment is
      assessed via microfaunal analysis of primarily calcareous benthic foraminifera.
      The findings suggest contemporaneous physical smothering at <=30m from the drill
      site, with a natural fauna reestablishing after drilling cessation indicating no
      long-term effect of drill cutting releases.

PMID- 29074253
TI  - Contrasting effects of ocean warming on different components of plant-herbivore
      interactions.
AB  - There is increasing uncertainty of how marine ecosystems will respond to rising
      temperatures. While studies have focused on the impacts of warming on individual
      species, knowledge of how species interactions are likely to respond is scant.
      The strength of even simple two-species interactions is influenced by several
      interacting mechanisms, each potentially changing with temperature. We used
      controlled experiments to assess how plant-herbivore interactions respond to
      temperature for three structural dominant macrophytes in the Mediterranean and
      their principal sea urchin herbivore. Increasing temperature differentially
      influenced plant-specific growth, sea urchin growth and metabolism, consumption
      rates and herbivore preferences, but not movement behaviour. Evaluating these
      empirical observations against conceptual models of plant-herbivore performance,
      it appears likely that while the strength of herbivory may increase for the
      tested macroalga, for the two dominant seagrasses, the interaction strength may
      remain relatively unchanged or even weaken as temperatures rise. These results
      show a clear set of winners and losers in the warming Mediterranean as the
      complex factors driving species interactions change.

PMID- 29074255
TI  - Quantitative structure-activity relationship of substituted imidazothiadiazoles
      for their binding against the ecdysone receptor of Sf-9 cells.
AB  - Imidazothiadiazoles (ITDs) are a class of potent nonsteroidal ecdysone agonists
      with larvicidal activity. Previously, we performed the Hansch-Fujita type of
      quantitative structure-activity relationship (QSAR) analysis for ITD analogs
      (Yokoi et al., Pestic. Biochem. Physiol.2015, 120, 40-50). The activity was
      reasonably explained by hydrophobicity and electronegativity of substituents on
      the imidazothiadiazole ring system. However, the limited data points (n = 8)
      hampered the examination of other physicochemical parameters. In the present
      study, we expanded the library of ITD congeners and evaluated their receptor
      binding affinity using intact Sf-9 cells. The QSAR analysis for the expanded set
      revealed the significance of the third physicochemical parameter, the negative
      steric effect for long substituents. We also evaluated the larvicidal activity of
      the synthesized compounds against Spodoptera litura; however, it was not
      correlated to the binding affinity. The results obtained here suggests that the
      pharmacokinetic properties must be improved to enhance the larvicidal activity of
      ITDs.

PMID- 29074256
TI  - Synthesis, anticancer, structural, and computational docking studies of 3
      benzylchroman-4-one derivatives.
AB  - A series of 3-Benzylchroman-4-ones were synthesized and screened for anticancer
      activity by MTT assay. The compounds were evaluated against two cancerous cell
      lines BT549 (human breast carcinoma), HeLa (human cervical carcinoma), and one
      noncancerous cell line vero (normal kidney epithelial cells). 3b was found to be
      the most active molecule against BT549 cells (IC50 = 20.1 uM) and 3h against HeLa
      cells (IC50 = 20.45 uM). 3b also exhibited moderate activity against HeLa cells
      (IC50 = 42.8 uM). The molecular structures of 3h and 3i were solved by single
      crystal X-ray crystallographic technique. Additionally, the molecular docking
      studies between the tumour suppressor protein p53 with the lead compound 3h,
      which exhibited better anticancer activity against HeLa cells was examined.

PMID- 29074254
TI  - Discovery of a class of diheteroaromatic amines as orally bioavailable CDK1/4/6
      inhibitors.
AB  - The discovery of a class of diheteroaromatic amines based on LY2835219 as cyclin
      dependent kinase (CDK1/4/6) inhibitors was described. The series was found to
      have much more improved CDK1 inhibition and potent in vitro anti-proliferative
      effects against cancer cell lines. The synthesis and structure-activity
      relationship studies of these compounds were reported. One promising compound was
      selected to evaluate as a novel lead compound after in vitro and in vivo
      profiling.

PMID- 29074257
TI  - Discovery and evaluation of Cav3.2-selective T-type calcium channel blockers.
AB  - We identified and characterized a series of pyrrole amides as potent, selective
      Cav3.2-blockers. This series culminated with the identification of pyrrole amides
      13b and 26d, with excellent potencies and/or selectivities toward the Cav3.1- and
      Cav3.3-channels. These compounds display poor physicochemical and DMPK
      properties, making their use difficult for in vivo applications. Nevertheless,
      they are well-suited for in vitro studies.

PMID- 29074258
TI  - Polyhydroxylated azetidine iminosugars: Synthesis, glycosidase inhibitory
      activity and molecular docking studies.
AB  - An efficient and practical strategy for the synthesis of unknown azetidine
      iminosugars (2S,3R,4S)-2-((R)-1,2-dihydroxyethyl)-3-hydroxy-4
      (hydroxymethyl)azetidine 2, (2S,3r,4R)-3-hydroxy-2,4-bis(hydroxymethyl)azetidine
      3 and (2S,3R,4S)-3-hydroxy-4-(hydroxymethyl)-N-methylazetidine-2-carboxylic acid
      4, starting from the d-glucose has been reported. The methodology involves
      preparation of the 3-amino-N-benzyloxycarbonyl-3-deoxy-6-O-tert
      butyldimethylsillyl-1,2-O-isopropylidene-alpha-d-glucofuranose 9, which was
      converted to the C-5-OMs derivative 11. Intramolecular nucleophilic displacement
      of the C-5-OMs group with in situ generated 3-amino functionality provided the
      required key azetidine ring skeletons 10 with additional hydroxymethyl group.
      Removal of 1,2-acetonide protection, followed by reduction and hydrogenolysis
      afforded azetidine iminosugar 2. Alternatively, removal of 1,2-acetonide group
      and chopping of C1-anomeric carbon gave C2-aldehyde that on reduction or
      oxidation followed by hydrogenolysis gave 2,4-bis(hydroxymethyl) azetidine
      iminosugars 3 and N-methylazetidine-2-carboxylic acid 4 respectively. The
      glycosidase inhibitory activity of 2-4 iminosugars was screened against various
      glycosidase enzymes and compared with a standard miglitol. Amongst synthesized
      targets, the compound 2 was found to be more potent amyloglucosidase inhibitor
      than miglitol. These results were supported by molecular docking studies.

PMID- 29074259
TI  - Socioeconomic status as an independent risk factor for severe late bowel toxicity
      after primary radiotherapy for cervical cancer.
AB  - OBJECTIVE: To evaluate the frequency of and risk factors for severe late bowel
      toxicity after curative radiotherapy in women treated for locally advanced
      cervical cancer. METHODS: Included were 515 women treated for locally advanced
      cervical cancer with primary radiotherapy with curative intent from 1992 to 2013.
      Bowel toxicity was graded according to the Common Terminology Criteria for
      Adverse Events. Associations between risk factors and severe late bowel toxicity
      were assessed using Cox proportional hazards regression models. RESULTS: Median
      follow-up was 78months. Fifty-nine patients developed severe late bowel toxicity.
      The actuarial 3-year and 5-year severe late bowel toxicity rates were both 13%.
      In the multivariable analysis, factors significantly associated with severe late
      bowel toxicity were: smoking (HR 2.59 [1.48-4.55]), severe acute bowel toxicity
      (HR 2.46 [1.24-4.49]), previous major abdominal surgery (HR 2.35 [1.20-4.60]),
      hypertension (HR 2.33 [1.23-4.40]), parametrial boost (HR 2.18 [1.10-4.33]), low
      socioeconomic status (HR 2.05 [1.17-3.59]) and low BMI (HR 0.93 [0.88-0.99]).
      First symptoms of severe late bowel toxicity were reported after a median follow
      up of 9months, but occurred up to 10years after end of treatment. Only one third
      of the patients with severe late bowel toxicity were referred to a
      gastroenterologist. CONCLUSIONS: Severe late bowel toxicity is a frequent
      complication of definitive radiotherapy for cervical cancer. Several independent
      risk factors were found which warrant further research. A standardized and
      structured approach in the early diagnostics and management of bowel toxicity is
      needed.

PMID- 29074261
TI  - Examining the relationship between higher educational attainment, trauma
      symptoms, and internalizing behaviors in child sexual abuse survivors.
AB  - The trauma symptoms of child sexual abuse (CSA) survivors don't end with the
      abuse, or even with the advent of adulthood. Instead, these symptoms can persist
      into all the realms of a survivor's life, including education, which sets the
      foundation for career advancement. This retrospective study of adult survivors of
      childhood sexual abuse (n=260) examined the relationships between trauma
      symptoms, dissociation, dissociative amnesia, anxiety, depression, sleep problems
      and higher education attainment. The purpose of this study was to determine if
      these factors are associated with higher education completion for childhood
      sexual abuse (CSA) survivors. Linear regressions and ANOVAs suggest that many of
      these variables are significantly associated with survivors' educational
      trajectory, and multiple linear regressions show that trauma symptoms (as
      measured by the Trauma Symptom Checklist-40), caregivers' education levels, and
      age at onset of abuse are significant predictors of decreased education levels.
      This information can provide insight into additional risk and protective factors
      for CSA survivors in order to enhance acute and long-term management of trauma
      symptoms to increase levels ofattainment of higher education.

PMID- 29074260
TI  - Rattling the border wall: Pathophysiological implications of functional and
      proteomic venom variation between Mexican and US subspecies of the desert
      rattlesnake Crotalus scutulatus.
AB  - While some US populations of the Mohave rattlesnake (Crotalus scutulatus
      scutulatus) are infamous for being potently neurotoxic, the Mexican subspecies C.
      s. salvini (Huamantlan rattlesnake) has been largely unstudied beyond crude
      lethality testing upon mice. In this study we show that at least some populations
      of this snake are as potently neurotoxic as its northern cousin. Testing of the
      Mexican antivenom Antivipmyn showed a complete lack of neutralisation for the
      neurotoxic effects of C. s. salvini venom, while the neurotoxic effects of the US
      subspecies C. s. scutulatus were time-delayed but ultimately not eliminated.
      These results document unrecognised potent neurological effects of a Mexican
      snake and highlight the medical importance of this subspecies, a finding
      augmented by the ineffectiveness of the Antivipmyn antivenom. These results also
      influence our understanding of the venom evolution of Crotalus scutulatus,
      suggesting that neurotoxicity is the ancestral feature of this species, with the
      US populations which lack neurotoxicity being derived states.

PMID- 29074263
TI  - Novel subfamilies of actin-regulating proteins.
AB  - Ability of actin to polymerise and depolymerise makes it essential to key
      functions of eukaryotic cell. The functioning of actin is controlled by a host of
      regulatory proteins, the repertoire of which in diatoms is known to remarkably
      differ from other organisms. We have performed a phylogenetic analysis of 521
      actin and actin-related proteins' aminoacid sequences, as well as 190 sequences
      of gelsolin family proteins from various genomic and transcriptomic datasets.
      Based on the results of this analysis, as well as on the presence of clade
      specific indels in some of the actin-related proteins, we describe a novel ARP
      subfamily, dubbed ARP12, which is specific to heterokonts and related organisms.
      We also describe two novel diatom-specific subfamilies, dGRC1 and dGRC2, among
      short gelsolin repeat-containing proteins.

PMID- 29074262
TI  - Photodynamic therapy as initial treatment for small choroidal melanomas.
AB  - PURPOSE: To evaluate Verteporfin photodynamic therapy (PDT) as primary treatment
      for small, posterior choroidal melanoma. DESIGN: Retrospective cohort review.
      SUBJECTS, PARTICIPANTS AND CONTROLS: Retrospective case note review of 20
      patients with small juxtapapillary and juxtafoveal choroidal melanomas treated
      with PDT at the Liverpool Ocular Oncology Clinic. METHODS: Patient and tumour
      characteristics, PDT session details, visual acuity and B-scan ultrasonography
      measurements as well as colour fundus photographs at each examination were
      collated and analysed. MAIN OUTCOME MEASURES: Local tumour control and Best
      Corrected Visual Acuity (BCVA). RESULTS: The 20 patients (14 male, 6 female) had
      a mean age of 61.2 years (range, 40-85) and were treated between 2001 and 2012.
      Seven tumours were amelanotic, while 13 were pigmented. Of 20 melanomas, 11 (55%)
      showed complete regression on B-scan ultrasonography and colour photography; five
      (25%) showed partial regression; four (20%) remained unchanged and two (10%)
      showed further growth, for which alternative standard treatment was required.
      Baseline BCVA was 0.1 logMAR (mean; range 0.0-0.6) compared to a post-PDT BCVA of
      0.4 logMAR (mean; range -0.2 to 1.7) over a follow-up of 60.0 months (mean; range
      25-156 months). CONCLUSIONS: PDT can induce tumour regression in a significant
      proportion of small, posterior, choroidal melanomas but is less reliable than
      other forms of therapy. It may have a role in patients with special visual
      requirements if they accept the increased risk of treatment failure requiring
      radiotherapy.

PMID- 29074264
TI  - Stroke treatment outcomes in hospitals with and without Stroke Units.
AB  - INTRODUCTION: Organisational capacity in terms of resources and care circuits to
      shorten response times in new stroke cases is key to obtaining positive outcomes.
      This study compares therapeutic approaches and treatment outcomes between
      traditional care centres (with stroke teams and no stroke unit) and centres with
      stroke units. METHODS: We conducted a prospective, quasi-experimental study
      (without randomisation of the units analysed) to draw comparisons between 2
      centres with stroke units and 4 centres providing traditional care through the
      neurology department, analysing a selection of agreed indicators for monitoring
      quality of stroke care. A total of 225 patients participated in the study. In
      addition, self-administered questionnaires were used to collect patients'
      evaluations of the service and healthcare received. RESULTS: Centres with stroke
      units showed shorter response times after symptom onset, both in the time taken
      to arrive at the centre and in the time elapsed from patient's arrival at the
      hospital to diagnostic imaging. Hospitals with stroke units had greater capacity
      to respond through the application of intravenous thrombolysis than centres
      delivering traditional neurological care. CONCLUSION: Centres with stroke units
      showed a better fit to the reference standards for stroke response time, as
      calculated in the Quick study, than centres providing traditional care through
      the neurology department.

PMID- 29074265
TI  - The effect of illusionary perception on mismatch negativity (MMN): An
      electroencephalography study.
AB  - Mismatch negativity (MMN) is a unique brain response elicited by any discernible
      change of features in a tone sequence. Although the occurrence of MMN is
      dependent upon the difference of a stimulus parameter, such as frequency or
      intensity, recent studies have suggested that MMN occurs as a result of a
      comparison between an internal representation created by perception and an
      incoming tone. The present study aimed to investigate MMN occurs based upon the
      physical properties of stimuli or as a result of the perception of the scale
      illusion. A scale illusion occurs during presentation of ascending and descending
      musical scales between C4 and C5. The tones of these scales are presented to the
      right and left ear alternately using a dichotic listening paradigm. Although the
      ascending/descending sequences are alternated between ears after each tone, we
      perceive the illusion of progressively ascending/descending tones as being
      separated by ear. The experiment was designed as an oddball task using the
      illusionary sequence and three different types of tone sequences as control
      conditions. Brain response to these sequences and infrequently presented deviants
      was measured using electroencephalography (EEG). All of the control sequences
      showed MMN in response to the deviant. However, the illusionary sequence did not
      result in a significant MMN. These results suggest that in the case of scale
      illusion, the occurrence of MMN is based upon the representation of tones created
      by perception, but not upon the physical properties of a tone sequence.

PMID- 29074266
TI  - Effective diffusion coefficients of DNAPL waste components in saturated low
      permeability soil materials.
AB  - Diffusion is regarded as the dominant transport mechanism into and out of low
      permeable subsurface lenses and layers in the subsurface. But, some reports of
      mass storage in such zones are higher than what might be attributable to
      diffusion, based on estimated diffusion coefficients. Despite the importance of
      diffusion to efforts to estimate the quantity of residual contamination in the
      subsurface, relatively few studies present measured diffusion coefficients of
      organic solutes in saturated low permeability soils. This study reports the
      diffusion coefficients of a trichloroethylene (TCE), and an anionic surfactant,
      Aerosol OT (AOT), in water-saturated silt and a silt-montmorillonite (25:75)
      mixture, obtained using steady-state experiments. The relative diffusivity ranged
      from 0.11 to 0.17 for all three compounds for the silt and the silt-clay mixture
      that was allowed to expand. In the case in which the swelling was constrained,
      the relative diffusivity was about 0.07. In addition, the relative diffusivity of
      13C-labeled TCE through a water saturated silt-clay mixture that had contacted a
      field dense non-aqueous phase liquid (DNAPL) for 18months was measured and
      equaled 0.001. These experimental results were compared with the estimates
      generated using common correlations, and it was found that, in all cases, the
      measured diffusion coefficients were significantly lower than the estimated.
      Thus, the discrepancy between mass accumulations observed in the field and the
      mass storage that can attributable to diffusion may be greater than previously
      believed.

PMID- 29074267
TI  - Microtomography-based Inter-Granular Network for the simulation of radionuclide
      diffusion and sorption in a granitic rock.
AB  - Field investigation studies, conducted in the context of safety analyses of deep
      geological repositories for nuclear waste, have pointed out that in fractured
      crystalline rocks sorbing radionuclides can diffuse surprisingly long distances
      deep into the intact rock matrix; i.e. much longer distances than those predicted
      by reactive transport models based on a homogeneous description of the properties
      of the rock matrix. Here, we focus on cesium diffusion and use detailed micro
      characterisation data, based on micro computed tomography, along with a grain
      scale Inter-Granular Network model, to offer a plausible explanation for the
      anomalously long cesium penetration profiles observed in these in-situ
      experiments. The sparse distribution of chemically reactive grains (i.e. grains
      belonging to sorbing mineral phases) is shown to have a strong control on the
      diffusive patterns of sorbing radionuclides. The computed penetration profiles of
      cesium agree well with an analytical model based on two parallel diffusive
      pathways. This agreement, along with visual inspection of the spatial
      distribution of cesium concentration, indicates that for sorbing radionuclides
      the medium indeed behaves as a composite system, with most of the mass being
      retained close to the injection boundary and a non-negligible part diffusing
      faster along preferential diffusive pathways.

PMID- 29074268
TI  - Waterpipe cafes are hazardous to your health: Determination of a waterpipe
      specific calibration factor.
AB  - INTRODUCTION: The use of a waterpipe to smoke tobacco has emerged as a popular
      trend in the United States. Waterpipe smoking establishments have had an
      increasing presence in the U.S., despite smoke-free air legislation. Dangers of
      waterpipe smoking have been documented, but less data has been gathered about the
      waterpipe cafe itself. This project sought to determine a waterpipe-specific
      calibration factor (CF) for measuring waterpipe aerosol, and field-test this CF
      by conducting surveillance on the existing waterpipe cafes of western and central
      New York. METHODS: Nine laboratory-controlled experiments were conducted to
      determine a waterpipe-specific CF. In the lab, two TSI SidePak AM510 Personal
      Aerosol Monitors and two sampling trains for gravimetric PM2.5 sampling were
      present during waterpipe smoking sessions (lasting 1-3h). Indoor air quality was
      assessed in 7 waterpipe cafes in three counties of New York, and real-time
      measurements of particulate matter (PM2.5) and carbon monoxide (CO) were
      obtained. RESULTS: Results from the 9 controlled waterpipe experiments determined
      a calibration factor of 0.38 (SD 0.08), which should be used to convert SidePak
      measurements to true PM2.5 measurements. When applying the CF to the measurements
      taken in the 7 public waterpipe venues, the mean PM2.5 concentration was
      515MUg/m3 micrograms per cubic meter (SD=338.8) while the mean ambient CO was
      20.5ppm (SD=18.3). The mean active smoking density was 2.41 waterpipes per 100m3
      of air. The PM2.5 levels increased with increasing active smoking density
      (rho=0.68, p=0.09). CONCLUSIONS: Applying the waterpipe-specific CF for the
      SidePak, 0.38, allowed for field assessments to be conducted in locations with
      waterpipe smoke to determine accurate particle exposure concentrations. The
      concentrations of both particulate matter and carbon monoxide were above
      established air quality standards and therefore increase the health risks of both
      patrons and workers of these establishments.

PMID- 29074269
TI  - Embracing the Nonindependence of the Environmental Filter: A Reply to Responses.

PMID- 29074270
TI  - How Green is 'Green' Energy?
AB  - Renewable energy is an important piece of the puzzle in meeting growing energy
      demands and mitigating climate change, but the potentially adverse effects of
      such technologies are often overlooked. Given that climate and ecology are
      inextricably linked, assessing the effects of energy technologies requires one to
      consider their full suite of global environmental concerns. We review here the
      ecological impacts of three major types of renewable energy - hydro, solar, and
      wind energy - and highlight some strategies for mitigating their negative
      effects. All three types can have significant environmental consequences in
      certain contexts. Wind power has the fewest and most easily mitigated impacts;
      solar energy is comparably benign if designed and managed carefully. Hydropower
      clearly has the greatest risks, particularly in certain ecological and
      geographical settings. More research is needed to assess the environmental
      impacts of these 'green' energy technologies, given that all are rapidly
      expanding globally.

PMID- 29074271
TI  - InSiCal - A tool for calculating calibration factors and activity concentrations
      in in situ gamma spectrometry.
AB  - In situ gamma spectrometry is a widely applied analysis technique for the
      determination of radioactivity levels in soil. Compared to traditional laboratory
      analysis of soil samples, in situ techniques offer a quick and low-cost way of
      obtaining accurate results from on-site measurements. However, although the
      technique is well-known, the dependence of in situ gamma spectrometry on complex
      and time-consuming calibration procedures as well as in-depth knowledge of the
      geometric distribution of the source in the ground deters many potential users
      from employing it in their routine work. Aiming to alleviate this issue, a
      software tool named InSiCal (In Situ gamma spectrometry Calculator) has been
      developed to make in situ gamma spectrometry more accessible to both experts and
      non-experts in the field. This is done by simplifying and streamlining both
      calibration and activity calculation through a simple and intuitive graphical
      user interface. Testing in real field conditions show that InSiCal is capable of
      yielding results which are in very good agreement with soil sample analyses, and
      that the results may be obtained using different detector types (HPGe, NaI, LaBr
      and CZT). Overall, InSiCal, provides results which are comparable in accuracy to
      laboratory measurements, indicating that it fulfills its purpose successfully.

PMID- 29074272
TI  - Melanin Transferred to Keratinocytes Resides in Nondegradative Endocytic
      Compartments.
AB  - Melanin transfer from melanocytes to keratinocytes and subsequent accumulation in
      the supranuclear region is a critical process in skin pigmentation and protection
      against UVR. We have previously proposed that the main mode of transfer between
      melanocytes and keratinocytes is through exo/endocytosis of the melanosome core,
      termed melanocore. In this study, we developed an in vitro uptake assay using
      melanocores secreted by melanocytes. We show that the uptake of melanocores, but
      not melanosomes, by keratinocytes is protease-activated receptor-2-dependent.
      Furthermore, we found that the silencing of the early endocytic regulator Rab5b,
      but not the late endocytic regulators Rab7a or Rab9a, significantly impairs
      melanocore uptake by keratinocytes. After uptake, we observed that melanin
      accumulates in compartments that are positive for both early and late endocytic
      markers. We found that melanin does not localize to either highly degradative or
      acidic organelles, as assessed by LysoTracker and DQ-BSA staining, despite the
      abundance of these types of organelles within keratinocytes. Therefore, we
      propose that melanocore uptake leads to storage of melanin within keratinocytes
      in hybrid endocytic compartments that are not highly acidic or degradative. By
      avoiding lysosomal degradation, these specialized endosomes may allow melanin to
      persist within keratinocytes for long periods.

PMID- 29074273
TI  - Real-Time Spatiotemporal Control of High-Intensity Focused Ultrasound Thermal
      Ablation Using Echo Decorrelation Imaging in ex Vivo Bovine Liver.
AB  - The ability to control high-intensity focused ultrasound (HIFU) thermal ablation
      using echo decorrelation imaging feedback was evaluated in ex vivo bovine liver.
      Sonications were automatically ceased when the minimum cumulative echo
      decorrelation within the region of interest exceeded an ablation control
      threshold, determined from preliminary experiments as -2.7 (log-scaled
      decorrelation per millisecond), corresponding to 90% specificity for local
      ablation prediction. Controlled HIFU thermal ablation experiments were compared
      with uncontrolled experiments employing two, five or nine sonication cycles.
      Means and standard errors of the lesion width, area and depth, as well as
      receiver operating characteristic curves testing ablation prediction performance,
      were computed for each group. Controlled trials exhibited significantly smaller
      average lesion area, width and treatment time than five-cycle or nine-cycle
      uncontrolled trials and also had significantly greater prediction capability than
      two-cycle uncontrolled trials. These results suggest echo decorrelation imaging
      is an effective approach to real-time HIFU ablation control.

PMID- 29074274
TI  - Cellular and functional actions of tofacitinib related to the pathophysiology of
      hibernoma development.
AB  - Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis.
      In the 2-year carcinogenicity study with tofacitinib, increased incidence of
      hibernoma (a neoplasm of brown adipose tissue [BAT]) was noted in female rats at
      >=30 mg/kg/day (>=41x human exposure multiples). Thus, signaling pathways within
      BAT were investigated by measuring BAT: weight, cell proliferation biomarkers,
      content of basal and prolactin-induced phosphorylated Signal Transducer and
      Activator of Transcription (STAT), and uncoupling protein 1 (UCP-1). The
      relationship between cardiovascular hemodynamics and plasma norepinephrine (NE)
      levels was also investigated. Tofacitinib administered to female rats at doses of
      10, 30, or 75 mg/kg/day for 14 days increased BAT weight at 75 mg/kg/day and cell
      proliferation at >=30 mg/kg/day. JAK inhibition, observed as lower pSTAT3 and
      pSTAT5 in BAT, was noted at >=10 mg/kg/day, while lower activity of BAT was
      observed as lower UCP-1 protein at >=30 mg/kg/day. In cultured brown adipocytes,
      prolactin-induced increase in pSTAT5 and pSTAT3 were inhibited by tofacitinib in
      a concentration-dependent manner. Tofacitinib lowered blood pressure, increased
      heart rate, and resulted in dose-dependent increases in circulating NE. Thus,
      JAK/STAT inhibition in BAT and sympathetic stimulation are two factors which
      might contribute to the genesis of hibernomas by tofacitinib in rats.

PMID- 29074275
TI  - Cigar burning under different smoking intensities and effects on emissions.
AB  - The effect of smoking intensity on cigar smoke emissions was assessed under a
      range of puff frequencies and puff volumes. In order to potentially reduce
      emissions variability and to identify patterns as accurately as possible, cigar
      weights and diameters were measured, and outliers were excluded prior to smoking.
      Portions corresponding to 25%, 50%, 75% and 100% of the cigar, measured down to
      the butt length, were smoked under several smoking conditions, to assess
      nicotine, CO and water yields. The remaining cigar butts were analysed for total
      alkaloids, nicotine, and moisture. Results showed accumulation effects during the
      burning process having a significant impact on smoke emission levels.
      Condensation and evaporation occur and lead to smoke emissions dependent on
      smoking intensity. Differences were observed for CO on one side as a gas phase
      compound and nicotine on the other side as a particulate phase compound. For a
      given intensity, while CO emission increases linearly as the cigar burns,
      nicotine and water emissions exhibited an exponential increase. Our
      investigations showed that a complex phenomena occurs during the course of cigar
      smoking which makes emission data: difficult to interpret, is potentially
      misleading to the consumer, and inappropriate for exposure assessment. The
      results indicate that, tobacco content and physical parameters may well be the
      most robust basis for product characterisation and comparison rather than smoke
      emission.

PMID- 29074276
TI  - Safety assessment of transgenic canola RF3 with bar and barstar gene on Sprague
      Dawley (SD) rats by 90-day feeding test.
AB  - Canola is one of the most important plant oilseed crops. To avoid the threat of
      herbicides, the RF3 line with bar gene and barstar gene was developed, which can
      act as glufosinate resistance resources and restore fertility in hybrid lines. To
      assess the food safety of transgenic canola RF3, 2.5%, 5% and 10% GM canola RF3
      and its non-GM isogenic line Drakkar were formulated into diet to feed Spragure
      Dawley (SD) rats for 90 days. The effects on the general growth and toxicological
      parameters, as well as gut microbiota of rats, were evaluated. Several
      significant differences on body weight, feed consumption, relative organ weight,
      hematology and serum biochemistry were observed among rats in the 90-day feeding
      test. However, these statistical differences were randomly observed among
      different groups and were not dose-related, which were not considered to be
      biologically significant. Furthermore, the results of bacterial 16S rRNA
      sequencing of fecal samples showed that the diets containing GM canola did not
      disturb the balance of gut microbiota. In conclusion, the canola RF3 is
      considered as safe and wholesome as the non-GM canola based on this 90-day
      feeding test and gut microbiota analysis.

PMID- 29074277
TI  - Physico-chemical properties of manufactured nanomaterials - Characterisation and
      relevant methods. An outlook based on the OECD Testing Programme.
AB  - Identifying and characterising nanomaterials require additional information on
      physico-chemical properties and test methods, compared to chemicals in general.
      Furthermore, regulatory decisions for chemicals are usually based upon certain
      toxicological properties, and these effects may not be equivalent to those for
      nanomaterials. However, regulatory agencies lack an authoritative decision
      framework for nanomaterials that links the relevance of certain physico-chemical
      endpoints to toxicological effects. This paper investigates various physico
      chemical endpoints and available test methods that could be used to produce such
      a decision framework for nanomaterials. It presents an overview of regulatory
      relevance and methods used for testing fifteen proposed physico-chemical
      properties of eleven nanomaterials in the OECD Working Party on Manufactured
      Nanomaterials' Testing Programme, complemented with methods from literature, and
      assesses the methods' adequacy and applications limits. Most endpoints are of
      regulatory relevance, though the specific parameters depend on the nanomaterial
      and type of assessment. Size (distribution) is the common characteristic of all
      nanomaterials and is decisive information for classifying a material as a
      nanomaterial. Shape is an important particle descriptor. The octanol-water
      partitioning coefficient is undefined for particulate nanomaterials. Methods,
      including sample preparation, need to be further standardised, and some new
      methods are needed. The current work of OECD's Test Guidelines Programme
      regarding physico-chemical properties is highlighted.

PMID- 29074278
TI  - High-alpha band synchronization across frontal, parietal and visual cortex
      mediates behavioral and neuronal effects of visuospatial attention.
AB  - Visuospatial attention prioritizes processing of attended visual stimuli. It is
      characterized by lateralized alpha-band (8-14 Hz) amplitude suppression in visual
      cortex and increased neuronal activity in a network of frontal and parietal
      areas. It has remained unknown what mechanisms coordinate neuronal processing
      among frontoparietal network and visual cortices and implement the attention
      related modulations of alpha-band amplitudes and behavior. We investigated
      whether large-scale network synchronization could be such a mechanism. We
      recorded human cortical activity with magnetoencephalography (MEG) during a
      visuospatial attention task. We then identified the frequencies and anatomical
      networks of inter-areal phase synchronization from source localized MEG data. We
      found that visuospatial attention is associated with robust and sustained long
      range synchronization of cortical oscillations exclusively in the high-alpha (10
      14 Hz) frequency band. This synchronization connected frontal, parietal and
      visual regions and was observed concurrently with amplitude suppression of low
      alpha (6-9 Hz) band oscillations in visual cortex. Furthermore, stronger high
      alpha phase synchronization was associated with decreased reaction times to
      attended stimuli and larger suppression of alpha-band amplitudes. These results
      thus show that high-alpha band phase synchronization is functionally significant
      and could coordinate the neuronal communication underlying the implementation of
      visuospatial attention.

PMID- 29074280
TI  - Premature brain aging in humans exposed to maternal nutrient restriction during
      early gestation.
AB  - BACKGROUND: Prenatal exposure to undernutrition is widespread in both developing
      and industrialized countries, causing irreversible damage to the developing
      brain, resulting in altered brain structure and decreased cognitive function
      during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now
      enabling studies of the effects of prenatal undernutrition during gestation on
      brain aging in late adulthood. METHODS: We hypothesized that study participants
      prenatally exposed to maternal nutrient restriction (MNR) would demonstrate
      altered brain structure resembling premature brain aging in late adulthood,
      expecting the effect being stronger in men. Utilizing the Dutch famine birth
      cohort (n = 118; mean age: 67.5 +/- 0.9 years), this study implements an
      innovative biomarker for individual brain aging, using structural neuroimaging.
      BrainAGE was calculated using state-of-the-art pattern recognition methods,
      trained on an independent healthy reference sample, then applied to the Dutch
      famine MRI sample, to evaluate the effects of prenatal undernutrition during
      early gestation on individual brain aging in late adulthood. RESULTS: Exposure to
      famine in early gestation was associated with BrainAGE scores indicative of an
      older-appearing brain in the male sample (mean difference to subjects born before
      famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in
      individual BrainAGE scores in the male sample, maternal age at birth, head
      circumference at birth, medical treatment of hypertension, history of cerebral
      incidences, actual heart rate, and current alcohol intake emerged to be the most
      influential variables (adjusted R2 = 0.63, p < 0.01). INTERPRETATION: The
      findings of our study on exposure to prenatal undernutrition being associated
      with a status of premature brain aging during late adulthood, as well as
      individual brain structure being shaped by birth- and late-life health
      characteristics, are strongly supporting the critical importance of sufficient
      nutrient supply during pregnancy. Interestingly, the status of premature brain
      aging in participants exposed to the Dutch famine during early gestation occurred
      in the absence of fetal growth restriction at birth as well as vascular pathology
      in late-life. Additionally, the neuroimaging brain aging biomarker presented in
      this study will further enable tracking effects of environmental influences or
      (preventive) treatments on individual brain maturation and aging in
      epidemiological and clinical studies.

PMID- 29074281
TI  - Corrigendum to "Promoting child-initiated social-communication in children with
      autism: Son-rise program intervention effects" [J. Commun. Disord. 46/5-6 (2013)
      495-506].

PMID- 29074279
TI  - Histological validation of diffusion MRI fiber orientation distributions and
      dispersion.
AB  - Diffusion magnetic resonance imaging (dMRI) is widely used to probe tissue
      microstructure, and is currently the only non-invasive way to measure the brain's
      fiber architecture. While a large number of approaches to recover the intra-voxel
      fiber structure have been utilized in the scientific community, a direct, 3D,
      quantitative validation of these methods against relevant histological fiber
      geometries is lacking. In this study, we investigate how well different high
      angular resolution diffusion imaging (HARDI) models and reconstruction methods
      predict the ground-truth histologically defined fiber orientation distribution
      (FOD), as well as investigate their behavior over a range of physical and
      experimental conditions. The dMRI methods tested include constrained spherical
      deconvolution (CSD), Q-ball imaging (QBI), diffusion orientation transform (DOT),
      persistent angular structure (PAS), and neurite orientation dispersion and
      density imaging (NODDI) methods. Evaluation criteria focus on overall agreement
      in FOD shape, correct assessment of the number of fiber populations, and angular
      accuracy in orientation. In addition, we make comparisons of the histological
      orientation dispersion with the fiber spread determined from the dMRI methods. As
      a general result, no HARDI method outperformed others in all quality criteria,
      with many showing tradeoffs in reconstruction accuracy. All reconstruction
      techniques describe the overall continuous angular structure of the histological
      FOD quite well, with good to moderate correlation (median angular correlation
      coefficient > 0.70) in both single- and multiple-fiber voxels. However, no method
      is consistently successful at extracting discrete measures of the number and
      orientations of FOD peaks. The major inaccuracies of all techniques tend to be in
      extracting local maxima of the FOD, resulting in either false positive or false
      negative peaks. Median angular errors are ~10 degrees  for the primary fiber
      direction and ~20 degrees  for the secondary fiber, if present. For most methods,
      these results did not vary strongly over a wide range of acquisition parameters
      (number of diffusion weighting directions and b value). Regardless of acquisition
      parameters, all methods show improved successes at resolving multiple fiber
      compartments in a voxel when fiber populations cross at near-orthogonal angles,
      with no method adequately capturing low to moderate angle (<60 degrees ) crossing
      fibers. Finally, most methods are limited in their ability to capture orientation
      dispersion, resulting in low to moderate, yet statistically significant,
      correlation with histologically-derived dispersion with both HARDI and NODDI
      methodologies. Together, these results provide quantitative measures of the
      reliability and limitations of dMRI reconstruction methods and can be used to
      identify relative advantages of competing approaches as well as potential
      strategies for improving accuracy.

PMID- 29074282
TI  - Clinical characteristics of patients with Takotsubo syndrome diagnosed without
      coronary artery evaluation: A retrospective nationwide study.
AB  - BACKGROUND: Although the current diagnostic criteria require that culprit
      coronary artery disease be ruled out before the diagnosis of Takotsubo syndrome
      (TTS) is made, performing coronary artery evaluation (CAE) in patients with
      serious backgrounds is sometimes challenging. METHODS: We conducted a
      retrospective cohort study using the Diagnosis Procedure Combination database in
      Japan. We identified patients in whom TTS was diagnosed at Japanese Circulation
      Society board-certified teaching hospitals from April 2011 to March 2014 and
      divided eligible patients into those who underwent CAE (coronary angiography or
      coronary computed tomography angiography) during hospitalization and those who
      did not. We compared the patient characteristics and in-hospital mortality
      between the groups. RESULTS: TTS was diagnosed in 5274 patients; 3255 (61.7%)
      underwent CAE and 2019 (38.3%) did not. Patients who did not undergo CAE were
      older; were more often male; showed higher proportions of an underweight status,
      impaired activities of daily living, and impaired consciousness; and showed
      higher proportions of several comorbidities (malignancy: 16.1% versus 5.7%;
      pneumonia: 15.0% versus 6.7%; and cerebrovascular disease: 13.7% versus 4.0%; all
      p<0.001) but lower proportions of coronary risk factors than patients who
      underwent CAE. Multivariable logistic regression analysis showed that older age
      [adjusted odds ratio: 0.98 (95% confidence interval: 0.97-0.98)], underweight
      [0.77 (0.65-0.91)], impaired consciousness [0.25 (0.18-0.35)], several
      comorbidities, and early requirement for surgery [0.13 (0.08-0.21)] were
      significantly associated with a lower likelihood of undergoing CAE. Crude in
      hospital mortality was significantly higher in patients without than with CAE
      (12.8% versus 4.9%; p<0.001). However, propensity score-matching analysis
      revealed no significant difference in in-hospital mortality between the two
      groups (8.8% versus 7.2%; p=0.252). CONCLUSIONS: Among patients diagnosed with
      TTS, CAE was less likely to be performed in patients with more serious
      backgrounds. CAE itself may not be associated with in-hospital mortality in
      patients with TTS.

PMID- 29074283
TI  - Re: Russo GI, Regis F, Castelli T, et al. A Systematic Review and Meta-analysis
      of the Diagnostic Accuracy of Prostate Health Index and 4-kallikrein Panel Score
      in Predicting Overall and High-grade Prostate Cancer. Clin Genitourin Cancer
      2017; 15:429-39.

PMID- 29074284
TI  - Retroperitoneal Robot-Assisted Versus Open Partial Nephrectomy for cT1 Renal
      Tumors: A Matched-Pair Comparison of Perioperative and Early Oncological
      Outcomes.
AB  - BACKGROUND: The objective of this study was to compare perioperative and early
      oncological outcomes of a matched cohort of patients who underwent
      retroperitoneal robot-assisted partial nephrectomy (RP-RAPN) and open partial
      nephrectomy (OPN) for clinically localized renal tumors. PATIENTS AND METHODS: We
      performed a retrospective analysis of patients who underwent RP-RAPN and OPN
      treated at 2 referral centers from January 2011 to December 2015. We focused on
      the following postoperative outcomes: warm ischemia time (WIT), operative time,
      blood loss, intra- and postoperative complications, estimated glomerular
      filtration rate (eGFR), hospital stay, and positive surgical margins. Because of
      inherent differences between patients in terms of baseline and disease
      characteristics, we relied on a propensity score-matched analysis to adjust for
      these differences. RESULTS: Globally, 104 patients were retrospectively evaluated
      and compared (52 matched individuals). RP-RAPN and OPN groups were comparable in
      terms of median age, body mass index, Charlson Comorbidity Index, clinical tumor
      size, preoperative aspects and dimensions used for anatomic classification and
      radius, exophyic/endophytic, nearness, anterior/posterior location score. Overall
      median operative time and WIT were significantly higher in the RP-RAPN group
      compared with the OPN group (P < .001). Intraoperative (3.8% vs. 0%) and
      postoperative (21.2% vs. 7.7%) complication rates were higher in the OPN group (P
      < .001). No statistically significant differences in postoperative eGFR were
      found. Median length of stay was significantly shorter in the RP-RAPN group (3
      vs. 5 days; P < .001). The incidence of positive surgical margins was comparable
      (3.8%). Trifecta was reached in 82.6% after RP-RAPN and 71.1% after OPN (P =
      .002). CONCLUSION: Retroperitoneal robot-assisted partial nephrectomy offered
      promising perioperative, early oncological, and functional outcomes, reinforcing
      the role of robotics as an alternative to open approach for partial nephrectomy.

PMID- 29074285
TI  - Local Salvage Treatment of Post-brachytherapy Recurrent Prostate Cancer via
      Theranostic Application of PSMA-labeled Lutetium-177.

PMID- 29074286
TI  - Endoscopic surgery of the olfactory cleft.
AB  - The olfactory cleft is the specific site of development of many tumours
      (respiratory epithelial adenomatoid hamartoma, intestinal-type adenocarcinoma,
      neuroblastoma, inverted papilloma, glomangiopericytoma, etc.) and is also the
      site of CSF rhinorrhoea via the cribriform plate (cribri-rhinorrhoea). Olfactory
      cleft surgery must therefore be considered to be a specific type of surgery,
      complementary to ethmoidal labyrinth surgery and anterior skull base surgery.
      Olfactory cleft tumours can be resected according to five different surgical
      procedures: olfactory cleft mucosal resection, partial resection of the olfactory
      cleft, total resection of the olfactory cleft, unilateral endoscopic anterior
      skull base resection, and bilateral endoscopic anterior skull base resection. The
      diagnosis and closure of cribri-rhinorrhoea (i.e. documented CSF rhinorrhoea,
      demonstrated to arise from the cribriform plate during endoscopic examination of
      the olfactory cleft under general anaesthesia in a patient with no localizing
      signs on imaging) completes this range of treatment options.

PMID- 29074287
TI  - Micromechanical analysis of brain's diffuse axonal injury.
AB  - Computational models are important tools which help researchers understand
      traumatic brain injury (TBI). A mechanistic multi-scale numerical approach is
      introduced to quantify diffuse axonal injury (DAI), the most important mechanism
      of TBI, induced by a mechanical insult at micro-scale regions of the white matter
      or voxels where fiber orientations are the same. Using the mechanical properties
      of a single axon with a viscoelastic constitutive relation and its functional
      failure in terms of electrophysiological impairment, a numerical 2D micro-level
      lattice method is implemented to directly analyze the percentage of injured axons
      in a voxel containing a bundle of axons all with the same orientation under
      biaxial stretches. Reference micro-injury maps are then developed with the input
      parameters based on the principal strain or stretch values and their direction
      with respect to axons, which provide the percentage of injured axons in the voxel
      of interest as the output. The methodology is independent of any statistical
      analyses of the accident data and medical reports to derive probabilistic injury
      risk curves for DAI. Avoiding a structurally detailed full finite element head
      model, this study proposes a micro-mechanical approach which considers the
      anatomical structure of neural axons in the white matter together with their
      mechanical properties using a numerical lattice method to analyze the brain's
      diffuse axonal injury. This work has the potential to help develop safer
      prevention tools and more effective diagnosis methods for DAI.

PMID- 29074288
TI  - Strategy quantification using body worn inertial sensors in a reactive agility
      task.
AB  - Agility performance is often evaluated using time-based metrics, which provide
      little information about which factors aid or limit success. The objective of
      this study was to better understand agility strategy by identifying biomechanical
      metrics that were sensitive to performance speed, which were calculated with data
      from an array of body-worn inertial sensors. Five metrics were defined
      (normalized number of foot contacts, stride length variance, arm swing variance,
      mean normalized stride frequency, and number of body rotations) that corresponded
      to agility terms defined by experts working in athletic, clinical, and military
      environments. Eighteen participants donned 13 sensors to complete a reactive
      agility task, which involved navigating a set of cones in response to a vocal
      cue. Participants were grouped into fast, medium, and slow performance based on
      their completion time. Participants in the fast group had the smallest number of
      foot contacts (normalizing by height), highest stride length variance
      (normalizing by height), highest forearm angular velocity variance, and highest
      stride frequency (normalizing by height). The number of body rotations was not
      sensitive to speed and may have been determined by hand and foot dominance while
      completing the agility task. The results of this study have the potential to
      inform the development of a composite agility score constructed from the list of
      significant metrics. By quantifying the agility terms previously defined by
      expert evaluators through an agility score, this study can assist in strategy
      development for training and rehabilitation across athletic, clinical, and
      military domains.

PMID- 29074289
TI  - Gait biomechanics of skipping are substantially different than those of running.
AB  - : The inherit injury risk associated with high-impact exercises calls for
      alternative ways to achieve the benefits of aerobic exercise while minimizing
      excessive stresses to body tissues. Skipping presents such an alternative,
      incorporating double support, flight, and single support phases. We used ground
      reaction forces (GRFs), lower extremity joint torques and powers to compare
      skipping and running in 20 healthy adults. The two consecutive skipping steps on
      each limb differed significantly from each other, and from running. Running had
      the longest step length, the highest peak vertical GRF, peak knee extensor
      torque, and peak knee negative and positive power and negative and positive work.
      Skipping had the greater cadence, peak horizontal GRF, peak hip and ankle
      extensor torques, peak ankle negative power and work, and peak ankle positive
      power. The second vs first skipping step had the shorter step length, higher
      cadence, peak horizontal GRF, peak ankle extensor torque, and peak ankle negative
      power, negative work, and positive power and positive work. The first skipping
      step utilized predominately net negative joint work (eccentric muscle action)
      while the second utilized predominately net positive joint work (concentric
      muscle action). The skipping data further highlight the persistence of net
      negative work performed at the knee and net positive work performed at the ankle
      across locomotion gaits. Evidence of step segregation was seen in distribution of
      the braking and propelling impulses and net work produced across the hip, knee,
      and ankle joints. CONCLUSIONS: Skipping was substantially different than running
      and was temporally and spatially asymmetrical with successive foot falls
      partitioned into a dominant function, either braking or propelling whereas
      running had a single, repeated step in which both braking and propelling actions
      were performed equally.

PMID- 29074290
TI  - Epigenetic effects of physical activity in elderly patients with cardiovascular
      disease.
AB  - Cardiovascular disease (CVD) is an important public health problem affecting
      especially the elderly. Over the past 20years, an increasing number of studies
      have examined its underlying pathophysiological mechanisms and new therapies are
      continually being discovered. However, despite considerable progress in CVD
      management, mortality and morbidity remain a major healthcare concern, and
      frequent hospital admissions compromise the daily life and social activities of
      these patients. Physical activity has emerged as an important non-pharmacological
      adjunctive therapy for CVD in older patients, especially for heart failure
      patients, exerting its beneficial effects on mortality, morbidity, and functional
      capacity. The mechanisms underlying the cardiovascular benefits of exercise are
      not wholly clear. Mounting evidence suggest that epigenetic modifications, such
      as DNA methylation, histone post-translational modifications (hPTMs) and non
      coding RNA, especially microRNAs (miRNAs), may be induced by physical activity.
      Recently, a number of miRNAs have been identified as key players in gene
      expression modulation by exercise. MiRNAs are synthesized by living cells and
      actively released into the bloodstream through different shuttles. The epigenetic
      information, thus carried and delivered, is involved in the interplay between
      environmental factors, including physical activity, and individual genetic make
      up. We review and discuss the effects of exercise on age-related CVDs, focusing
      on circulating miRNA (c-miRNAs) modulation. Epigenetic mechanisms may have
      clinical relevance in CVD prevention and management; since they can be modified,
      insights into the implications of lifestyle-related epigenetic changes in CVD
      etiology may help develop therapeutic protocols of exercise training that can be
      suitable and effective for elderly patients.

PMID- 29074291
TI  - Standardisation and half-life of 89Zr.
AB  - The nuclide 89Zr is being tested for the labelling of compounds with long blood
      circulation times. It decays by beta plus emission (22.8%) and by electron
      capture (77.2%) to 89Y. Its half-life has been determined by following the decay
      rate with two measurement systems; an Ionisation Chamber and an HPGe detector.
      The combination of six results gives a value of T1/2 = 78.333 (38) h, slightly
      lower than the DDEP recommended value of 78.42 (13) h. This radionuclide has also
      been standardised by liquid scintillation counting, 4pigamma counting and
      coincidence techniques.

PMID- 29074292
TI  - Subarachnoid hemorrhage induces neuronal nitric oxide synthase phosphorylation at
      Ser1412 in the dentate gyrus of the rat brain.
AB  - INTRODUCTION: We previously demonstrated that cyclic AMP-dependent protein kinase
      (PKA) phosphorylates neuronal nitric oxide synthase (nNOS) at Ser1412 in the
      hippocampal dentate gyrus after forebrain ischemia; this phosphorylation event
      activates NOS activity and might contribute to depression after cerebral
      ischemia. In this study, we revealed chronological and topographical changes in
      the phosphorylation of nNOS at Ser1412 immediately after subarachnoid hemorrhage
      (SAH). METHODS: In a rat single-hemorrhage model of SAH, the hippocampus and
      adjacent cortex were collected up to 24 h after SAH. Samples from rats that were
      not injected with autologous blood were used as controls. NOS was partially
      purified from crude samples via an ADP-agarose gel. Levels of nNOS, nNOS
      phosphorylated at Ser1412 (p-nNOS), PKA, and p-PKA at Thr197 were studied in the
      rat hippocampus and cortex using Western blot analyses and immunohistochemistry.
      RESULTS: According to the Western blot analysis, levels of p-nNOS at Ser1412 were
      significantly increased in the hippocampus, but not in the cortex, between 1 and
      3 h after SAH. Immunohistochemistry revealed the phosphorylation of nNOS at
      Ser1412 and PKA at Thr197 in the dentate gyrus, but not in the CA1 area, 1 h
      after SAH. An injection of saline instead of blood also significantly increased
      levels of p-nNOS at Ser1412 in the hippocampus 1 h after the injection.
      CONCLUSIONS: An immediate increase in intracranial pressure (ICP) might induce
      transient cerebral ischemia and promote the PKA-mediated phosphorylation of nNOS
      at Ser1412 in the dentate gyrus. This signal transduction pathway induces the
      excessive production of nitric oxide (NO) and might be involved in cognitive
      dysfunction after SAH.

PMID- 29074293
TI  - Relationship between asymmetric dimethylarginine, nitrite and genetic
      polymorphisms: Impact on erectile dysfunction therapy.
AB  - Sildenafil is the most used treatment of erectile dysfunction, however a large
      part of patients do not respond to therapy. This drug enhances nitric oxide (NO)
      signaling, and therefore factors that alter NO production may impact this drug
      responsiveness. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of
      all NO synthases, and is metabolized by Dimethylarginine Dimethilaminohydrolase
      (DDAH) 1 and 2. Here we aimed to assess the relationship between plasma levels of
      ADMA and nitrite (marker of nitric oxide production) with Sildenafil
      responsiveness. We also studied genetic polymorphisms in DDAH1 and DDAH2 genes
      and their relation with biochemical and clinical data. Were included here 140
      patients, divided in Clinical Erectile Dysfunction (CED) or Post-Prostatectomy
      Erectile Dysfunction (PPED) groups. Erectile function was evaluated before and
      after Sildenafil on-demand treatment using the International Index for Erectile
      Function Questionnaire. We have found that nitrite was associated with worse
      response to Sildenafil (r = - 0.25, P = 0.040). rs1554597 and rs18582 DDAH1
      polymorphisms were associated with changes in ADMA levels in CED (B = - 0.23, P =
      0.002; B = - 0.15, P = 0.017 for both variant genotypes, respectively). Finally,
      DDAH2 polymorphisms were associated with altered responsiveness to Sildenafil in
      PPED (B = +0.19, P = 0.027).

PMID- 29074294
TI  - 221st ENMC International Workshop:: Foot Surgery in Charcot-Marie-Tooth disease.
      10-12 June 2016, Naarden, The Netherlands.

PMID- 29074295
TI  - Corrigendum to 'Rare diagnosis of telethoninopathy (LGMD2G) in a Turkish patient'
      [Neuromuscular Disorders 27 (2017) 856-860].

PMID- 29074297
TI  - Hierarchical, imbalanced pro-inflammatory cytokine networks govern the
      pathogenesis of chronic arthropathies.
AB  - BACKGROUND: Chronic inflammatory arthropathies, such as rheumatoid arthritis
      (RA), spondyloarthritis, including psoriatic arthritis (PsA), ankylosing
      spondyloarthritis (AS), osteoarthritis (OA), and intervertebral disc degenerative
      disease (DDD) constitute major public health problems that are anticipated to
      grow significantly as the human population ages. However, many aspects concerning
      the molecular mechanisms underlying their onset and progression remain unclear.
      DESIGN: This narrative review critically analyzes the molecular mechanisms
      underlying the inflammation-associated pathogenesis of the aforementioned joint
      diseases. This includes, in particular, the major role played by several key
      soluble factors (such as cytokines and the associated signaling pathways,
      designated as "fragile nodes") produced by local cells and recruited to the
      joints' immune cells, whose elimination by specific drugs has dramatically
      improved the diseases' symptomatology and outcome in human clinical trials or in
      rodent arthritis models. HYPOTHESIS AND THE AIM OF THIS REVIEW: We hypothesize
      that the pathogenesis of chronic inflammatory arthropathies is governed by
      hierarchical, imbalanced pro-inflammatory cytokine networks (HIPICNs) (comprising
      a combination of fragile nodes) that are created during the development of both
      autoimmune (RA, PsA, and AS) and non-autoimmune (OA and DDD) disorders. The main
      aim of this review is to provide evidence that despite substantial
      pathobiological differences between these arthropathies, the HIPICNs created are
      quite common, thus justifying the merging of these disorders mechanistically and
      suggesting that these common mechanisms exist in the onset and progression of
      different joint diseases.

PMID- 29074296
TI  - International Workshop:: Outcome measures and clinical trial readiness in primary
      mitochondrial myopathies in children and adults. Consensus recommendations. 16-18
      November 2016, Rome, Italy.

PMID- 29074298
TI  - Variable cartilage degradation in mice with diet-induced metabolic dysfunction:
      food for thought.
AB  - OBJECTIVE: Human cohort studies have demonstrated a role for systemic metabolic
      dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the
      mechanisms underlying this metabolic phenotype of OA, we examined cartilage
      degradation in the knees of mice from different genetic backgrounds in which a
      metabolic phenotype was established by various dietary approaches. DESIGN: Wild
      type C57BL/6J mice and genetically modified mice (hCRP, LDLr-/-. Leiden and
      ApoE*3Leiden.CETP mice) based on C57BL/6J background were used to investigate the
      contribution of inflammation and altered lipoprotein handling on diet-induced
      cartilage degradation. High-caloric diets of different macronutrient composition
      (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration
      to induce a metabolic phenotype with aggravated cartilage degradation relative to
      controls. RESULTS: Metabolic phenotypes were confirmed in all studies as mice
      developed obesity, hypercholesteremia, glucose intolerance and/or insulin
      resistance. Aggravated cartilage degradation was only observed in two out of the
      twelve experimental setups, specifically in long-term studies in male hCRP and
      female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr-/-. Leiden mice did not develop
      HFD-induced OA under the conditions studied. Osteophyte formation and synovitis
      scores showed variable results between studies, but also between strains and
      gender. CONCLUSIONS: Long-term feeding of high-caloric diets consistently induced
      a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast,
      the induction of articular cartilage degradation proved variable, which suggests
      that an additional trigger might be necessary to accelerate diet-induced OA
      progression. Gender and genetic modifications that result in a humanized pro
      inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were
      identified as important contributing factors.

PMID- 29074299
TI  - Angiopoietin-like protein 2 promotes chondrogenic differentiation during bone
      growth as a cartilage matrix factor.
AB  - OBJECTIVE: Chondrocyte differentiation is crucial for long bone growth. Many
      cartilage extracellular matrix (ECM) proteins reportedly contribute to
      chondrocyte differentiation, indicating that mechanisms underlying chondrocyte
      differentiation are likely more complex than previously appreciated. Angiopoietin
      like protein 2 (ANGPTL2) is a secreted factor normally abundantly produced in
      mesenchymal lineage cells such as adipocytes and fibroblasts, but its loss
      contributes to the pathogenesis of lifestyle- or aging-related diseases. However,
      the function of ANGPTL2 in chondrocytes, which are also differentiated from
      mesenchymal stem cells, remains unclear. Here, we investigate whether ANGPTL2 is
      expressed in or functions in chondrocytes. METHODS: First, we evaluated Angptl2
      expression during chondrocyte differentiation using chondrogenic ATDC5 cells and
      wild-type epiphyseal cartilage of newborn mice. We next assessed ANGPTL2 function
      in chondrogenic differentiation and associated signaling using Angptl2 knockdown
      ATDC5 cells and Angptl2 knockout mice. RESULTS: ANGPTL2 is expressed in
      chondrocytes, particularly those located in resting and proliferative zones, and
      accumulates in ECM surrounding chondrocytes. Interestingly, long bone growth was
      retarded in Angptl2 knockout mice from neonatal to adult stages via attenuation
      of chondrocyte differentiation. Both in vivo and in vitro experiments show that
      changes in ANGPTL2 expression can also alter p38 mitogen-activated protein kinase
      (MAPK) activity mediated by integrin alpha5beta1. CONCLUSION: ANGPTL2 contributes
      to chondrocyte differentiation and subsequent endochondral ossification through
      alpha5beta1 integrin and p38 MAPK signaling during bone growth. Our findings
      provide insight into molecular mechanisms governing communication between
      chondrocytes and surrounding ECM components in bone growth activities.

PMID- 29074300
TI  - Dendritic cells pulsed with Pythium insidiosum (1,3)(1,6)-beta-glucan, Heat
      inactivated zoospores and immunotherapy prime naive T cells to Th1
      differentiation in vitro.
AB  - Pythiosis is a life-threatening disease caused by the fungus-like microorganism
      Pythium insidiosum that can lead to death if not treated. Since P. insidiosum has
      particular cell wall characteristics, pythiosis is difficult to treat, as it does
      not respond well to traditional antifungal drugs. In our study, we investigated a
      new immunotherapeutic approach with potential use in treatment and in the
      acquisition of immunity against pythiosis. Dendritic cells from both human and
      mouse, pulsed with P. insidiosum heat-inactivated zoospore, (1,3)(1,6)-beta
      glucan and the immunotherapeutic PitiumVac(r) efficiently induced naive T cell
      differentiation in a Th1 phenotype by the activation of specific Th1 cytokine
      production in vitro. Heat-inactivated zoospores showed the greatest Th1 response
      among the tested groups, with a significant increase in IL-6 and IFN-gamma
      production in human cells. In mice cells, we also observed a Th17 pathway
      induction, with an increase on the IL-17A levels in lymphocytes cultured with
      beta-glucan pulsed DCs. These results suggest a potential use of DCs pulsed with
      P. insidiosum antigens as a new therapeutic strategy in the treatment and
      acquisition of immunity against pythiosis.

PMID- 29074301
TI  - Identification of immune biomarkers related to disease progression and treatment
      efficacy in human visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a potentially fatal disease, in which the
      treatment based on chemotherapy is considered toxic. The cure of disease is
      associated with the life-long Th1-type immunity against the infection. The Th1
      related cytokines production by peripheral blood mononuclear cells (PBMCs) seems
      to be crucial for host control of parasite load and clinical cure. In the current
      study, we used five proteins (IgE-dependent histamine-releasing factor [HRF],
      LiHyD, LiHyV, LiHyT and LiHyp6) recently shown to be antigenic and/or immunogenic
      in the canine VL, aiming to evaluate the antigen-specific antibody levels and
      cytokine production in PBMCs culture supernatants collected from VL patients
      before and after anti-VL treatment. In the results, when PBMCs were exposed to
      rHRF, rLiHyD and rLiHyT, higher IFN-gamma and lower IL-10 levels were observed in
      all patients that were treated and clinically cured. Analysis of specific
      antibody subclasses was in line with in vitro cellular response, since a higher
      IgG2 production was found in the treated and cured patients, when compared to the
      IgG1 subclass levels. In addition, evaluating the diagnostic efficacy of the
      recombinant molecules, the rHRF, rLiHyD and rLiHyT proteins showed the best
      results in the serology assays to identify all VL patients, as well as these
      antigens were not recognized by antibodies in sera from non-infected subjects or
      those with leishmaniasis-related diseases. Our results corroborate the view that
      clinical cure of VL is associated with a sustained Th1-related response, and
      indicate the potential use of rHRF, rLiHyD and rLiHyT as immune biomarkers of VL
      treatment.

PMID- 29074302
TI  - Endogenous antibody responses to mucin 1 in a large multiethnic cohort of
      patients with breast cancer and healthy controls: Role of immunoglobulin and
      Fcgamma receptor genes.
AB  - High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane
      bound glycoprotein that is overexpressed in patients with breast cancer, are
      associated with good prognosis. This suggests that endogenous anti-MUC1
      antibodies have a protective effect and, through antibody-mediated host
      immunosurveillance mechanisms, might contribute to a cancer-free state. To test
      this possibility, we characterized a large number of multiethnic patients with
      breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to
      determine whether the magnitude of anti-MUC1 antibody responsiveness was
      associated with particular immunoglobulin GM (gamma marker), KM (kappa marker),
      and Fcgamma receptors (FcgammaR) genotypes. After adjusting for the confounding
      variables in a multivariate analysis, we found no significant difference in the
      levels of anti-MUC1 IgG antibodies between patients and cancer-free controls.
      However, in patients and controls, particular GM, KM, and FcgammaR genotypes
      individually or epistatically-were significantly associated with the levels of
      anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if
      confirmed in an independent investigation, could help identify individuals most
      likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1
      overexpressing malignancies.

PMID- 29074303
TI  - Effect of dexmedetomidine on the minimum infusion rate of propofol preventing
      movement in dogs.
AB  - OBJECTIVE: To determine the effect of dexmedetomidine on induction dose and
      minimum infusion rate of propofol preventing movement (MIRNM). STUDY DESIGN:
      Randomized crossover, unmasked, experimental design. ANIMALS: Three male and
      three female healthy Beagle dogs weighing 10.2 +/- 2.8 kg. METHODS: Dogs were
      studied on three occasions at weekly intervals. Premedications were 0.9% saline
      (treatment P) or dexmedetomidine (1 MUg kg-1, treatment PLD; 2 MUg kg-1,
      treatment PHD) intravenously. Anesthesia was induced with propofol (2 mg kg-1 and
      then 1 mg kg-1 every 15 seconds) until intubation. Anesthesia was maintained for
      90 minutes in P with propofol (0.5 mg kg-1 minute-1) and saline, in PLD with
      propofol (0.35 mg kg-1 minute-1) and dexmedetomidine (1 MUg kg-1 hour-1), and in
      PHD with propofol (0.3 mg kg-1 minute-1) and dexmedetomidine (2 MUg kg-1 hour-1).
      The stimulus (50 V, 50 Hz, 10 ms) was applied to the antebrachium, and propofol
      infusion was increased or decreased by 0.025 mg kg-1 minute-1 based on a positive
      or negative response, respectively. Data were analyzed using a mixed-model anova
      and presented as mean +/- standard error. RESULTS: Propofol induction doses were
      8.68 +/- 0.57 (P), 6.13 +/- 0.67 (PLD) and 4.78 +/- 0.39 (PHD) mg kg-1 and
      differed among treatments (p < 0.05). Propofol MIRNM values were 0.68 +/- 0.13,
      0.49 +/- 0.16 and 0.26 +/- 0.05 mg kg-1 minute-1 for P, PLD and PHD,
      respectively. Propofol MIRNM decreased 59% in PHD (p < 0.05). Plasma propofol
      concentrations were 14.04 +/- 2.30 (P), 11.30 +/- 4.30 (PLD) and 7.96 +/- 0.72
      (PHD) MUg mL-1 and dexmedetomidine concentrations were 0.68 +/- 0.12 (PLD) and
      0.89 +/- 0.08 (PHD) ng mL-1 at MIRNM determination. CONCLUSIONS AND CLINICAL
      RELEVANCE: Dexmedetomidine (1 and 2 MUg kg-1) decreased propofol induction dose.
      Dexmedetomidine (2 MUg kg-1 hour-1) resulted in a significant decrease in
      propofol MIRNM.

PMID- 29074305
TI  - Scleral lens after intracorneal ring segments in patients with keratoconus.
AB  - BACKGROUND: To report the use of scleral lens (ScCL) to improve vision in
      patients having keratoconus who had intracorneal ring segment (ICRS) surgery.
      METHODS: Two eyes of two keratoconus patients fitted with ScCL (PROSE -
      prosthetic replacement of the ocular surface ecosystem, USA) after having
      undergone ICRS surgery are reported as noncomparative interventional case series.
      The ICRS implanted were INTACs and kerarings. Indications, visual acuity with
      ScCL, complications and follow-up are reported. RESULTS: Case 1 underwent ScCL
      trial as he was referred for keratoplasty for being contact lens intolerant after
      ICRS surgery. Case 2 was intolerant to both corneal rigid gas permeable (RGP)
      lens and soft contact lens (SCL). 18.5 and 18mm diameter ScCLs were dispensed to
      Case 1 and 2 respectively. The ScCLs had adequate corneal clearance with no
      corneal touch. There was no staining of the cornea or vascularization with the
      lens use. Case 1 complained of double images during trial with different Front
      surface eccentricity (FSE). A ScCL that did not cause diplopia was ordered. At
      four months of lens wear, the patient had diplopia with ScCL, which cleared when
      second lens with changed FSE was dispensed. Case 2 used SCL for five years before
      ScCL was fitted. He used the same ScCLs for five years. ScCL use resulted in
      improved comfort and visual acuity of 20/20. No complications were noted.
      CONCLUSIONS: ScCL may be tried in patients who have ICRS and are intolerant to
      corneal RGP or SCL and before subjecting such patients to keratoplasty.

PMID- 29074306
TI  - The efficacy of tea tree face wash, 1, 2-Octanediol and microblepharoexfoliation
      in treating Demodex folliculorum blepharitis.
AB  - PURPOSE: To compare the efficacy of Dr Organic Tea Tree Face Wash, OcuSoft Lids
      Scrub Plus and the BlephExTM device at treating of Demodex folliculorum
      blepharitis. METHODS: Eighty-six subjects (33 males/36 females) were enrolled in
      a randomised controlled interventional treatment study. Subjects completed a dry
      eye symptom questionnaire and were assessed for presence of Demodex folliculorum.
      Subjects were divided into three groups according to treatment: Dr Organic Tea
      Tree Face Wash (A) (n=28), OcuSoft Lid Scrub Plus (B) (n=30), or in-house lid
      scrub with the BlephExTM device before nightly lid scrubs with OcuSoft Lid Scrub
      Plus (C) (n=28). Subjects were advised to clean their eyelids nightly for four
      weeks. Each subject was re-assessed for symptoms and Demodex folliculorum
      blepharitis after two weeks and four weeks of treatment. RESULTS: The quantity of
      Demodex folliculorum was significantly reduced after four weeks of treatment in
      all three groups (p<0.05). Overall, there was no difference in efficacy between
      the three treatments (p>0.1). Symptoms reported by subjects were significantly
      improved after two and four weeks of treatment (p<0.05). Overall, there was no
      difference in efficacy between the three treatments to reduce symptoms after two
      or four weeks (p= 0.813 and p=0.646 respectively). CONCLUSION: All three methods
      tested have shown good ability to reduce Demodex folliculorum quantity, improve
      subjective symptoms and help treat Demodex folliculorum blepharitis.

PMID- 29074304
TI  - Depolarizing, inhibitory GABA type A receptor activity regulates GABAergic
      synapse plasticity via ERK and BDNF signaling.
AB  - gamma-aminobutyric acid (GABA) begins as the key excitatory neurotransmitter in
      newly forming circuits, with chloride efflux from GABA type A receptors (GABAARs)
      producing membrane depolarization, which promotes calcium entry, dendritic
      outgrowth and synaptogenesis. As development proceeds, GABAergic signaling
      switches to inhibitory hyperpolarizing neurotransmission. Despite the evidence of
      impaired GABAergic neurotransmission in neurodevelopmental disorders, little is
      understood on how agonist-dependent GABAAR activation controls the formation and
      plasticity of GABAergic synapses. We have identified a weakly depolarizing and
      inhibitory GABAAR response in cortical neurons that occurs during the transition
      period from GABAAR depolarizing excitation to hyperpolarizing inhibitory
      activity. We show here that treatment with the GABAAR agonist muscimol mediates
      structural changes that diminish GABAergic synapse strength through postsynaptic
      and presynaptic plasticity via intracellular Ca2+ stores, ERK and BDNF/TrkB
      signaling. Muscimol decreases synaptic localization of surface gamma2 GABAARs and
      gephyrin postsynaptic scaffold while beta2/3 non-gamma2 GABAARs accumulate in the
      synapse. Concurrent with this structural plasticity, muscimol treatment decreases
      synaptic currents while enhancing the gamma2 containing benzodiazepine sensitive
      GABAAR tonic current in an ERK dependent manner. We further demonstrate that
      GABAAR activation leads to a decrease in presynaptic GAD65 levels via BDNF/TrkB
      signaling. Together these data reveal a novel mechanism for agonist induced
      GABAergic synapse plasticity that can occur on the timescale of minutes,
      contributing to rapid modification of synaptic and circuit function.

PMID- 29074308
TI  - Second-order grasp planning reflects sensitivity to inertial factors.
AB  - Previous studies have shown that people's grasps of objects are tuned to the
      objects' inertial properties. In most of those studies, information obtained
      about the attunement of the grasps to the objects' inertial properties was
      limited to first-order grasp planning (i.e., planning of grasps based on
      immediate task demands). We investigated attunement of grasps to an object's
      inertial properties in the context of second-order grasp planning (i.e., planning
      of grasps based on subsequent task demands). In Experiment 1, participants
      grasped a horizontal rod whose right or left end would be brought down onto a
      target. Consistent with previous findings, participants grasped the rod so as to
      complete the movement with a thumb-up posture, using an overhand grasp when the
      right end of the rod was to be brought to the target and an underhand grasp when
      the left end was to be brought to the target. They also grasped the rod to the
      right of center, but more so when doing this with an underhand than when with an
      overhand grasp. In Experiment 2, participants performed the same task with an
      asymmetrically weighted rod. Changes in subjects' grasps in Experiment 2 compared
      to Experiment 1 suggested that participants grasped the rod based on the inertial
      properties of the rod in a way that took advantage of the pendular properties of
      the hand-plus-object.

PMID- 29074307
TI  - The role of conscious control in maintaining stable posture.
AB  - This study aimed to examine the relationship between conscious control of
      movements, as defined by the Theory of Reinvestment (Masters & Maxwell, 2008;
      Masters, Polman, & Hammond, 1993), and both traditional and complexity-based COP
      measures. Fifty-three young adults (mean age=20.93+/-2.53years), 39 older adults
      with a history of falling (mean age=69.23+/-3.84years) and 39 older adults
      without a history of falling (mean age=69.00+/-3.72years) were asked to perform
      quiet standing balance in single- and dual-task conditions. The results showed
      that higher scores on the Movement Specific Reinvestment Scale (MSRS; Masters,
      Eves, & Maxwell, 2005; Masters & Maxwell, 2008), a psychometric measure of the
      propensity for conscious involvement in movement, were associated with larger
      sway amplitude and a more constrained (less complex) mode of balancing in the
      medial-lateral direction for young adults only. Scores on MSRS explained
      approximately 10% of total variation in the medial-lateral sway measures. This
      association was not apparent under dual-task conditions, during which a secondary
      task was used to limit the amount of cognitive resources available for conscious
      processing. No relationship between postural control and score on the MSRS was
      found for either older adult fallers or non-fallers. Possible explanations for
      these results are discussed.

PMID- 29074309
TI  - Fully Artificial Exosomes: Towards New Theranostic Biomaterials.
AB  - Bionanotechnology routes have been recently developed to produce fully artificial
      exosomes: biomimetic particles designed to overcome certain limitations in
      extracellular vesicle (EV) biology and applications. These particles could soon
      become true therapeutic biomaterials. Here, we outline their current preparation
      techniques, their explored and future possibilities, and their present limits.

PMID- 29074311
TI  - Investigation into the pulmonary inflammopathology of exposure to nickel oxide
      nanoparticles in mice.
AB  - We investigated the effects of nickel oxide nanoparticles (NiONPs) on the
      pulmonary inflammopathology. NiONPs were intratracheally installed into mice, and
      lung injury and inflammation were evaluated between 1 and 28 days. NiONPs caused
      significant increases in LDH, total protein, and IL-6 and a decrease in IL-10 in
      the BALF and increases in 8-OHdG and caspase-3 in lung tissues at 24 h. Airway
      inflammation was present in a dose-dependent manner from the upper to lower
      airways at 24 h of exposure as analyzed by SPECT. Lung parenchyma inflammation
      and small airway inflammation were observed by CT after NiONP exposure. 8-OHdG in
      lung tissues had increased with formation of fibrosis at 28 days. Focal adhesion
      was the most important pathways identified at 24 h as determined by protemics,
      whereas glutathione metabolism was the most important identified at 28 days. Our
      results demonstrated the pulmonary inflammopathology caused by NiONPs based on
      image-to-biochemical approaches.

PMID- 29074313
TI  - Psoriasiform lesions: Uncommon presentation of glucagonoma.

PMID- 29074310
TI  - Challenges and opportunities in developing targeted molecular imaging to
      determine inner ear defects of sensorineural hearing loss.
AB  - The development of inner ear gene carriers and delivery systems has enabled
      genetic defects to be repaired and hearing to be restored in mouse models. Today,
      promising advances in translational therapies provide confidence that targeted
      molecular therapy for inner ear diseases will be developed. Unfortunately, the
      currently available non-invasive modalities, such as Computerized Tomography scan
      or Magnetic Resonance Imaging provide insufficient resolution to identify most
      pathologies of the human inner ear, even when the current generation of contrast
      agents is utilized. The development of targeted contrast agents may play a
      critical role in determining the cause of, and treatment for, sensorineural
      hearing loss. Such agents should be able to pass through the cochlea barriers,
      possess minimal cytotoxicity, and easily conjugate to a targeting agent, without
      distorting the anatomic details. This review focuses on a series of contrast
      agents which may fit these criteria for potential clinical application.

PMID- 29074312
TI  - Understanding the Patient Experience with Carcinoid Syndrome: Exit Interviews
      from a Randomized, Placebo-controlled Study of Telotristat Ethyl.
AB  - PURPOSE: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended
      to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl
      was evaluated in TELESTAR, a Phase III study for patients who had carcinoid
      syndrome with at least 4 bowel movements (BMs) per day and who were receiving
      somatostatin analogue therapy. This interview substudy was conducted to provide
      insight into the patient experience in TELESTAR and to help understand whether
      reductions in BM frequency (the primary end point) and other symptoms were
      clinically meaningful. METHODS: Participating sites were asked to invite (before
      randomization) all eligible patients to telephone interviews scheduled at the end
      of the double-blind treatment period. Patients and interviewers were blinded to
      treatment. FINDINGS: All 35 interviewed participants reported diarrhea and/or
      excessive BMs at baseline. Patients reported that these symptoms negatively
      affected emotional, social, physical, and occupational well-being. Prespecified
      criteria for treatment response (achieving >=30% reduction in BM frequency for at
      least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and
      1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described
      clinically meaningful reductions in BM frequency and were very satisfied with the
      ability of the study drug to control their carcinoid syndrome symptoms. Overall,
      reports of being very satisfied were observed in 12 patients taking telotristat
      ethyl and 0 taking placebo. IMPLICATIONS: Patient interviews revealed that
      TELESTAR patients, at baseline, were significantly affected by their high BM
      frequency. Patient reports of their clinical trial experience supported the
      significance of the primary end point and clinical responder analysis in
      TELESTAR, helping identify and understand clinically meaningful change produced
      by telotristat ethyl.

PMID- 29074314
TI  - Dysphagia caused by intramural oesophageal pseudodiverticulosis: An unusual
      endoscopic finding.

PMID- 29074315
TI  - Basal cell carcinoma of the scalp with destruction and invasion into the
      calvarium and dura mater: Report of 7 cases and review of literature.
AB  - Basal cell carcinoma (BCC) is the most common skin malignancy in humans. Giant
      BCC is a rarer entity that is characterised by aggressive biological behaviour.
      Intracranial invasion by a BCC on the scalp is extremely rare. The gold standard
      treatment of BCCs is represented by surgical excision with a wide variety of
      reconstructive techniques. In this paper, we describe the largest series to date
      of recurrent BCCs with intracranial extension involving the dura mater. We report
      recurrent giant BCC of the scalp with dura mater invasion in 7 patients. All
      patients in this series previously had more than 2 operations. Gadolinium
      enhanced MRI revealed neoplastic invasion of the meninges and brain tissues. All
      patients had a multi-disciplinary team approach with the surgical margins ranging
      between 1 and 2 cm depending on the location and the size of the tumour. 5 of the
      patients underwent reconstruction of the skin defect by antero-lateral thigh
      flap, 1 patient underwent reconstruction with pedicled myocutaneous (trapezius)
      flap, and 1 with a pedicled myocutaneous latissimus dorsi flap. There was a mean
      follow-up of 5.3 years. 2 patients died due to cardio-pulmonary complications in
      the neuro-intensive care unit. A multi-disciplinary team approach and early
      aggressive tumour resection followed by sophisticated reconstructive and
      aesthetic procedures appears to be a reliable and realistic treatment modality
      for invasive BCC.

PMID- 29074316
TI  - Outcome of Gamma Knife radiosurgery for trigeminal neuralgia associated with
      neurovascular compression.
AB  - We reviewed 130 patients from 1999 to 2012 to evaluate whether neurovascular
      compression (NVC) has prognostic value for pain relief in idiopathic trigeminal
      neuralgia (TN) treated by Gamma Knife radiosurgery (GKRS). Patients were assigned
      to one of the following groups based on NVC identified by MRI: no NVC, small
      vessel NVC, and large vessel (defined as part of the vertebrobasilar arterial
      system) NVC. Follow-up ranged from 4 to 14years. Primary outcome was pain graded
      by the Barrow Neurological Institute (BNI) pain scale. Successful pain control
      was defined asa score within Grade I-IIIb. Among the 130 patients, 53 had no
      neurovascular compression (group 1), 60 had a small vessel NVC (group 2), and 17
      had a large vessel NVC (group 3). Successful pain control was 85% in group 1, 75%
      in group 2, and 88% in group 3 (X2=2.480, p=.289). Secondary outcome was new
      onset facial numbness which was 21% in group 1, 28% in group 2, and 35% in group
      3 (X2=1.683, p=.431). NVC did not affect pain outcome for TN patients treated by
      GKRS. The lack of poorer response with large vessel NVC that has been reported in
      literature may be explained by treatment of multiple 4mm shots (as opposed to a
      single shot in 11/17 patients) to cover a larger compression area of the nerve
      root by a tortuous vessel.

PMID- 29074317
TI  - Alteration of cortical excitability and its modulation by Miglustat in Niemann
      Pick disease type C.
AB  - Niemann-Pick type C (NP-C) is a rare, neurodegenerative, lysosomal storage
      disease. Cortical excitability using different transcranial magnetic stimulation
      (TMS) protocols together with clinical and neuropsychological testing was
      longitudinally assessed in a patient with NP-C. Cerebellar inhibition, a measure
      for the integrity of the cerebello-thalamo-cortical network, was impaired. Short
      latency afferent inhibition, a measure for cholinergic transmission, and
      cognitive functions were also impaired and improved under Miglustat treatment.
      Short interval intracortical facilitation, a marker for glutamatergic
      neurotransmission, was absent initially but increased after treatment with
      Miglustat. Our results provide new insights into pathophysiological mechanisms of
      NP-C and the response to Miglustat treatment.

PMID- 29074318
TI  - Pedicle screws with modular head vs. preassembled head used in cortical bone
      trajectory: Can pars and pedicle fractures be prevented in osteoporotic bone?
AB  - Pars and pedicle fractures as a result of CBT (cortical bone trajectory) during
      pedicle screw placement have been reported. The primary aim of the study is to
      compare the fracture rate between screws with modular heads to screws with
      standard pre-assembled tulip heads. The secondary aim of the study is to
      determine the potential variables that can be identified prior to instrumentation
      in order to predict risk of fractures. Twenty-four fresh frozen lumbar vertebrae
      were obtained from five different cadavers. Anatomical landmark measurements were
      obtained. Right and left pedicles of each vertebra were randomly instrumented
      with the preassembled head screws (n=24) and modular head screws (n=24) under
      video recording. X-ray images were obtained for measuring relative angle
      deviations between tapped and final screw trajectories. Finally, pullout tests
      were performed. Seventeen out of twenty-four (70.8%) of the spinous processes had
      to be excised in order to obtain proper trajectories. Six fractures occurred with
      pre-assembled head screws versus one in the modular head screws (p=0.04).
      Distances from the midline to the medial wall of the pedicle were marginally
      significant as a predictor for fracture (p=0.08). The pullout loads between both
      types of screws were not statistically different (p=0.38). Age was better
      correlated with pullout load than absolute bone density value (p<0.001). In
      conclusion, modular head screws had a significantly lower fracture rate than pre
      assembled head screws for cortical bone trajectory in osteoporotic bone. There
      was no clear anatomic variable that could be measured pre-operatively to predict
      potential fracture risk in CBT.

PMID- 29074319
TI  - Mobile Technology for Treatment Augmentation in Veteran Smokers With
      Posttraumatic Stress Disorder.
AB  - INTRODUCTION: The purpose of this study is to examine the feasibility and
      acceptability of incorporating a mobile application, Stay Quit Coach, into an
      integrated care smoking-cessation treatment protocol for veterans with
      posttraumatic stress disorder (PTSD). METHODS: Participants included veteran
      smokers aged 18-69 years with PTSD. The integrated care protocol includes eight
      weekly PTSD-informed cognitive behavioral therapy sessions for smoking cessation,
      followed by monthly booster sessions and a prescription for standard smoking
      cessation medications if desired. Participants used Stay Quit Coach as desired.
      Outcome measures at 3-month follow-up included: adherence (sessions attended), 30
      day point-prevalence abstinence bioverified with carbon monoxide <6 parts per
      million, past-30 day mean daily cigarette use, exhaled carbon monoxide, nicotine
      dependence, and PTSD symptom severity. Repeated outcomes were analyzed with
      random-intercept linear mixed models. Data were collected in 2015-2016 and
      analyses were conducted in 2016-2017. RESULTS: Participants (n=20) were 95% male
      and 5% female; mean age 41.4 (SD=16.2) years. Thirteen participants (65%)
      attended all scheduled sessions, four (20%) did not adhere to the protocol on
      schedule, and three (15%) were lost to follow-up. At 3-month follow-up, six of 17
      completers (35.3%) had bioverified 30-day point-prevalence abstinence. Nicotine
      dependence, carbon monoxide levels, and past 30-day cigarette use significantly
      decreased and PTSD symptoms were unchanged from baseline to follow-up.
      Participants self-reported using Stay Quit Coach 2.5 (SD=2.2) days/week; 15 of 17
      (88.2%) reported using Stay Quit Coach <30 minutes/week; two of 17 (11.8%)
      reported using Stay Quit Coach 30-60 minutes/week. CONCLUSIONS: Although results
      must be interpreted with caution given the lack of control group and small sample
      size, findings indicate that integrating Stay Quit Coach into integrated care was
      feasible and acceptable.

PMID- 29074321
TI  - Predicting the Feasibility of Correcting Mechanical Axis in Large Varus
      Deformities With Unicompartmental Knee Arthroplasty.
AB  - BACKGROUND: Due to disappointing historical outcomes of unicompartmental knee
      arthroplasty (UKA), Kozinn and Scott proposed strict selection criteria,
      including preoperative varus alignment of <=15 degrees , to improve the outcomes
      of UKA. No studies to date, however, have assessed the feasibility of correcting
      large preoperative varus deformities with UKA surgery. The study goals were
      therefore to (1) assess to what extent patients with large varus deformities
      could be corrected and (2) determine radiographic parameters to predict
      sufficient correction. METHODS: In 200 consecutive robotic-arm assisted medial
      UKA patients with large preoperative varus deformities (>=7 degrees ), the
      mechanical axis angle (MAA) and joint line convergence angle (JLCA) were measured
      on hip-knee-ankle radiographs. It was assessed what number of patients were
      corrected to optimal (<=4 degrees ) and acceptable (5 degrees -7 degrees )
      alignment, and whether the feasibility of this correction could be predicted
      using an estimated MAA (eMAA, preoperative MAA-JLCA) using regression analyses.
      RESULTS: Mean preoperative MAA was 10 degrees  of varus (range, 7 degrees -18
      degrees ), JLCA was 5 degrees  (1 degrees -12 degrees ), postoperative MAA was 4
      degrees  of varus (-3 degrees  to 8 degrees ), and correction was 6 degrees  (1
      degrees -14 degrees ). Postoperative optimal alignment was achieved in 62% and
      acceptable alignment in 36%. The eMAA was a significant predictor for optimal
      postoperative alignment, when corrected for age and gender (P < .001).
      CONCLUSION: Patients with large preoperative varus deformities (7 degrees -18
      degrees ) could be considered candidates for medial UKA, as 98% was corrected to
      optimal or acceptable alignment, although cautious approach is needed in
      deformities >15 degrees . Furthermore, it was noted that the feasibility of
      achieving optimal alignment could be predicted using the preoperative MAA, JLCA,
      and age.

PMID- 29074320
TI  - HPV Vaccination Among Foreign-Born Women: Examining the National Health Interview
      Survey 2013-2015.
AB  - INTRODUCTION: Human papillomavirus vaccination is less prevalent among foreign
      born than U.S.-born women and may lead to disparities in human papillomavirus
      related cancers in the future. There is limited research on factors associated
      with vaccination uptake between these two groups. This study examined the
      association between place of birth and human papillomavirus vaccine uptake, and
      what determinants of vaccination attenuate this relationship. METHODS: The 2013
      2015 National Health Interview Survey data on women was analyzed in 2016, to
      determine differences in prevalence of human papillomavirus vaccination between
      foreign- and U.S.-born women. Multivariate binary logistic regression analysis
      was used to examine the association between foreign-born status and human
      papillomavirus vaccine initiation, after controlling for health insurance status,
      having a usual source of care, obstetrician/gynecologist visits, Pap tests,
      length of U.S. residency, and citizenship. RESULTS: Human papillomavirus
      vaccination prevalence varied significantly among women born in different regions
      of the world. European and South-American women had the highest vaccination rates
      among all foreign-born women. Compared with U.S.-born women, foreign-born women
      were significantly less likely to report human papillomavirus vaccine initiation.
      This relationship was partially attenuated after adjusting for the covariates.
      Among foreign-born women, Asians were significantly less likely to report human
      papillomavirus vaccination uptake than white women. Additionally, living in the
      U.S. for >5 years was significantly associated with vaccine initiation, but
      attenuated by U.S. citizenship status. CONCLUSIONS: Public health interventions
      to improve human papillomavirus vaccination need to be developed to address
      multicultural audiences with limited access to health insurance and health care.

PMID- 29074323
TI  - Patella Resurfacing in Total Knee Arthroplasty: A Series of 1280 Patients at
      Midterm Follow-Up.
AB  - BACKGROUND: The management of patella in total knee arthroplasty (TKA) is a
      controversial topic. The elevated risk of patellofemoral complications seems to
      support those who are not eager to perform such procedure. The aim of this study
      is to carry out a retrospective assessment of patients who underwent patellar
      resurfacing during TKA from 2004 to 2009. METHODS: From January 1, 2004, to
      December 31, 2009, 1280 patients underwent TKA with patellar prosthesis
      implantation. Of them, 861 patients (639 women and 222 men with an average age of
      67.7 +/- 12.3 years) were available for a telephonic interview consisting of the
      questions included in the Knee Pain Score (KPS). Patients presenting KPS >36 and
      those subjected to reoperation were then evaluated clinically and radiologically.
      RESULTS: Of the 861 patients included in the study, 801 showed a KPS <36. Among
      the remaining 60 patients, 33 had a KPS >36, while 27 had been reoperated at the
      target knee. In the former case, a decrease in normal Insall-Salvati index and
      patellar tilt values (from 1.08 to 1.02 and from 9.3 to 9.1, respectively) and
      average anatomic axis (from -2.6 degrees  to 1.1 degrees ) was found comparing
      preoperative with last follow-up evaluation. Only in 0.6% of the cases of
      reintervention, patellofemoral complications were found to be the cause.
      CONCLUSION: This study conducted on a large and homogenous group of patients
      confirms a very low rate of complications related to patella resurfacing during
      TKA.

PMID- 29074322
TI  - Satisfactory Short-Term Results of Navigation-Assisted Gap-Balancing Total Knee
      Arthroplasty Using Ultracongruent Insert.
AB  - BACKGROUND: The use of highly conforming ultracongruent (UC) polyethylene insert
      is bone-preserving and became a relatively common alternative to the conventional
      posterior stabilized total knee arthroplasty (TKA) design. The purpose of this
      study was to analyze the short-term clinical and radiologic results of UC insert
      TKA using the navigation-assisted gap-balancing technique. METHODS: Two hundred
      thirty-three knees were operated with a mean follow-up period of 8.1 years
      (minimum of 5 years). Radiologic and clinical outcomes were assessed before
      operation and at latest follow-up using the Knee Society Score and Western
      Ontario and McMaster Universities Osteoarthritis Index score. For statistical
      analysis, paired sample t-test and analysis of variance were used. Significance
      was considered as P < .05. RESULTS: According to the preoperative deformities
      (valgus, mild varus, and moderate varus), there were 23 cases (9.9%) of valgus
      deformity, 180 cases (77.3%) of mild varus deformity, and 30 cases (12.9%) of
      moderate varus deformity. Overall, the results at mean 8.1 years revealed an
      improvement in mean Knee Society Score (54 +/- 12 to 92 +/- 3) and mean Western
      Ontario and McMaster Universities Osteoarthritis Index scores (62 +/- 14 to 17 +/
      3). Overall, 220 of 233 cases (94.4%) were in neutral alignment (between -3
      degrees  and +3 degrees ) at latest follow-up. There were no migrating or
      shifting prosthesis that should be considered as possible failure. There was 0%
      component revision rate. CONCLUSION: Navigation-assisted gap-balancing technique
      using UC insert TKA had satisfactory short-term outcome. Strict gap-balancing
      technique using the offset-type-force-controlled-spreader-system aided in the
      satisfactory results.

PMID- 29074324
TI  - Does Calipered Kinematically Aligned TKA Restore Native Left to Right Symmetry of
      the Lower Limb and Improve Function?
AB  - BACKGROUND: Kinematically aligned total knee arthroplasty (KA TKA) strives to
      restore the native left to right symmetry of the lower limb; however, the
      reproducibility of achieving this target is unknown. The present study determined
      the proportion of patients with left to right symmetry and the improvement in
      patient-reported function after calipered KA TKA. METHODS: A review of 562
      postoperative scanograms identified 102 patients (53 women) with a KA TKA in one
      limb, no other skeletal abnormalities in either limb, and symmetrical rotation
      between limbs on the scanogram. All patients were treated with primary TKA that
      used caliper measurement of the thicknesses of the femoral bone and tibial bone
      resections to kinematically align the components. The hip-knee-ankle (HKA) angle,
      distal lateral femoral angle (DLFA), and proximal medial tibial angle (PMTA) were
      measured. Patient-reported Oxford Knee Score (OKS) measured preoperative and
      postoperative functions. RESULTS: The proportion of patients with a difference in
      the HKA angle, DLFA, and PMTA between limbs within +/-3 degrees , >3 degrees 
      varus, and <-3 degrees  valgus was 95%, 2%, and 3%, respectively, for the HKA
      angle; 97%, 1%, and 2%, respectively, for the DLFA; and 97%, 2%, and 1%,
      respectively, for the PMTA. The mean OKS improved from 20 preoperatively to 44
      points (range 18-48 points) at 15 months postoperatively. CONCLUSION: Calipered
      KA TKA restored native left to right symmetry of the HKA angle, DLFA, and PMTA in
      nearly all patients with negligible risk of varus alignment of the tibial
      component with respect to the native tibial joint line. The mean postoperative
      OKS indicated clinically important improvement in patient-reported function.

PMID- 29074326
TI  - 48th Union World Conference on Lung Health.

PMID- 29074325
TI  - Critical care medicine: a call for papers for ISICEM.

PMID- 29074327
TI  - Thyrotropic activity of corticotropin-releasing hormone in an altricial bird
      species, the zebra finch (Taeniopygia guttata).
AB  - In chicken, corticotropin-releasing hormone (CRH) acts as a thyrotropin (TSH)
      releasing factor, mediated by the type 2 CRH receptor (CRHR2) on the thyrotropes
      of the pituitary gland. It is not known whether CRH also controls TSH release in
      non-precocial avian species that have a different pattern of thyroidal activity
      during their life cycle. Therefore, we investigated the TSH-releasing capacity of
      CRH in an altricial species, the zebra finch (Taeniopygia guttata). Cellular
      localisation of type 1 CRH receptor (CRHR1) and CRHR2 mRNA in the pituitary was
      determined by in situ hybridisation, combined with immunohistochemical staining
      of pituitary thyrotropes. In addition, isolated pituitary glands were stimulated
      with CRH to determine the effect on TSH release. Lastly, the mRNA levels of
      hormones and receptors involved in the control of thyroidal and adrenal function
      were measured by qPCR in zebra finch chicks between hatching and fledging, and in
      adults. Most of the hypophyseal CRHR2 mRNA co-localised with thyrotropes, whereas
      CRHR1 mRNA was found inbetween thyrotropes. Pituitary glands stimulated in vitro
      with CRH showed increased secretion of TSH-like activity. Pituitary CRHR2 mRNA
      expression decreased while pituitary TSHB mRNA and brain CRH mRNA levels
      increased towards fledging, similar as seen in chicken hatching. These results
      suggest that CRHR2 expressed on thyrotropes is likely mediating CRH-induced TSH
      release in altricial avian species like it does in precocial species, and that
      the increased thyroid hormone levels towards fledging in altricial birds are the
      result of increased hypothalamic stimulation, in which the thyrotropic activity
      of CRH may initially play a role.

PMID- 29074330
TI  - Motor dysfunction as an intermediate phenotype across schizophrenia and other
      psychotic disorders: Progress and perspectives.
AB  - Primary motor abnormalities (PMA), as found in patients with schizophrenia, are
      quantitatively and qualitatively distinct markers of motor system abnormalities.
      PMA have been often referred to phenomena that are present across schizophrenia
      spectrum disorders. A dysfunction of frontoparietal and subcortical networks has
      been proposed as core pathophysiological mechanism underlying the expression of
      PMA. However, it is unclear at present if such mechanisms are a common within
      schizophrenia and other psychotic disorders. To address this question, we review
      recent neuroimaging studies investigating the neural substrates of PMA in
      schizophrenia and so-called "nonschizophrenic nonaffective psychoses" (NSNAP)
      such as schizophreniform, schizoaffective, brief psychotic, and other unspecified
      psychotic disorders. Although the extant data in patients with schizophrenia
      suggests that further investigation is warranted, MRI findings in NSNAP are less
      persuasive. It is unclear so far which PMA, if any, are characteristic features
      of NSNAP or, possibly even specific for these disorders. Preliminary data suggest
      a relationship between relapsing-remitting PMA in hyper-/hypokinetic cycloid
      syndromes and neurodegenerative disorders of the basal ganglia, likely reflecting
      the transnosological relevance of subcortical abnormalities. Despite this
      evidence, neural substrates and mechanisms underlying PMA that are common in
      schizophrenia and NSNAP cannot be clearly delineated at this stage of research.
      PMA and their underlying brain circuits could be promising intermediate phenotype
      candidates for psychotic disorders, but future multimodal neuroimaging studies in
      schizophrenia and NSNAP patients and their unaffected first-degree relatives are
      needed to answer fundamental transnosologic questions.

PMID- 29074328
TI  - Fasting blood glucose and risk of prostate cancer: A systematic review and meta
      analysis of dose-response.
AB  - AIM: This study aimed to test the dose-response relationship between fasting
      blood glucose (FBG) levels and risk of prostate cancer. METHODS: A systematic
      search was done of PubMed and Scopus from their inception up to January 2017.
      Prospective and retrospective studies reporting risk estimates of prostate cancer
      for two or more categories of blood glucose levels were identified, and two
      independent authors extracted the information. Relative risk (RR) was calculated
      using random-effects models and pooled. RESULTS: Ten prospective cohort studies,
      one nested case-control study, one case-cohort study and three case-control
      studies (total n=1,214,947) involving 12,494 cases of prostate cancer were
      reviewed. The pooled RR of prostate cancer for the highest vs. lowest category of
      FBG was 0.88 (95% CI: 0.78-0.98, I2=25.5%, n=15 studies). A 10mg/dL increment in
      FBG level was not associated with risk of prostate cancer (0.98, 95% CI: 0.96
      1.00, I2=45.4%, n=11 studies). Subgroup analyses yielded a significant inverse
      association only in the subgroup of cohort studies. Non-linear dose-response meta
      analysis showed a very slight decrement in risk with increasing FBG levels.
      Sensitivity analyses using cohort studies showed a steep decrease in risk along
      with an increase in FBG from baseline levels of ~70mg/dL across prediabetes and
      diabetes ranges. CONCLUSION: Higher FBG levels are associated with lower risk of
      prostate cancer in cohort studies, but not in case-control studies, findings that
      limit interpretation of our present results.

PMID- 29074329
TI  - Degree of ketonaemia and its association with insulin resistance after
      dapagliflozin treatment in type 2 diabetes.
AB  - BACKGROUND: Euglycaemic ketoacidosis has been reported after sodium-glucose
      cotransporter 2 (SGLT2) inhibitor treatment. However, the degree of ketonaemia
      and its metabolic effects have not been well investigated. Our study examined the
      degree of ketonaemia induced by SGLT2 inhibition and its association with
      metabolic profiles in type 2 diabetes mellitus (T2DM). METHODS: Biochemical
      parameters, including insulin, glucagon, free fatty acid (FFA), beta
      hydroxybutyrate (BHB) and acetoacetate (ACA) levels, were measured in 119 T2DM
      patients after dapagliflozin treatment for>3 months, and compared with a matched
      control group. RESULTS: Levels of total ketones, BHB and ACA were significantly
      higher in the dapagliflozin group than in the control group: 283.7+/-311.0 vs
      119.8+/-143.8MUmol/L; 188.3+/-226.6 vs 78.0+/-106.7MUmol/L; and 94.1+/-91.3 vs
      41.8+/-39.1MUmol/L, respectively (all P<0.001). After dapagliflozin treatment,
      BHB was higher than the upper limit of normal (>440MUmol/L) in 13 (10.9%)
      patients who had no relevant symptoms. BHB level after dapagliflozin treatment
      correlated positively with HbA1c (r=0.280), FFA levels (r=0.596) and QUICKI
      (r=0.238), and negatively with BMI (r=-0.222), insulin-to-glucagon ratio (r=
      0.199) and HOMA-IR (r=-0.205; all P<0.05). On multivariable linear regression
      analysis, QUICKI was independently associated with BHB level. CONCLUSION: Ketone
      levels were higher in T2DM patients treated with dapagliflozin than in controls,
      but with no clinical symptoms or signs of ketonaemia. Low-grade ketonaemia after
      dapagliflozin treatment may also be associated with improved insulin sensitivity.

PMID- 29074331
TI  - Intra-individual variability and psychotic-like experiences in adolescents:
      Findings from the ALSPAC cohort.
AB  - Clinical and epidemiological studies have demonstrated associations between
      elevated intra-individual variability (IIV) of reaction time and psychotic
      disorders. However, little attention has been paid to the relationship between
      performance stability and psychotic-like experiences (PLE) in adolescence, before
      psychotic disorder onset. Data from 6702 children from the Avon Longitudinal
      Study of Parents and Children (ALSPAC) were used to address this issue. Children
      took part in a semi-structured clinical interview regarding psychotic symptoms at
      age 12 and 18, and reaction time variability was assessed at age 13 and 15.
      Children who had elevated IIV at age 15 were more likely to report suspected or
      definite PLE at age 18, with larger associations being found for more frequent or
      bizarre symptoms. Elevated IIV at age 15 was also associated with persistent PLE
      between age 12 and 18. These findings tentatively suggest that elevated IIV in
      early adolescence may be predictive of later PLE, and offer some support for the
      notion of a psychosis continuum.

PMID- 29074332
TI  - Improving individual predictions: Machine learning approaches for detecting and
      attacking heterogeneity in schizophrenia (and other psychiatric diseases).
AB  - Psychiatric diseases are very heterogeneous both in clinical manifestation and
      etiology. With the recent rise of using machine learning techniques to attempt to
      diagnose and prognose these disorders, the issue of heterogeneity becomes
      increasingly important. With the growing interest in personalized medicine, it
      becomes even more important to not only classify someone as a patient with a
      certain disorder, its treatment needs a more precise definition of the underlying
      neurobiology, since different biological origins of the same disease may require
      (very) different treatments. We review the possible contributions that machine
      learning techniques could make to explore the heterogeneous nature of psychiatric
      disorders with a focus on schizophrenia. First we will review how heterogeneity
      shows up and how machine learning, or multivariate pattern recognition methods in
      general, can be used to discover it. Secondly, we will discuss the possible uses
      of these techniques to attack heterogeneity, leading to improved predictions and
      understanding of the neurobiological background of the disorder.

PMID- 29074333
TI  - Improvement of portal venous pressure in cirrhotic rat livers by systemic
      treatment with adipose tissue-derived mesenchymal stromal cells.
AB  - BACKGROUND AIMS: Portal hypertension is the main cause of complications in
      cirrhosis caused primarily by extensive fibrosis. Both anti-fibrotic and pro
      fibrotic properties of mesenchymal stromal cells (MSCs) have been described in
      various animal models of liver fibrosis. Therefore, the impact of MSCs on portal
      hypertension and fibrosis should be investigated in an animal model of liver
      cirrhosis. METHODS: The effect of systemic treatment with adipose tissue-derived
      MSCs, pre-differentiated into hepatocytic cells, was investigated in a rat model
      of liver cirrhosis induced by chronic inhalation of carbon tetrachloride.
      RESULTS: Chronic intoxication with carbon tetrachloride increased the portal
      venous pressure, which was significantly attenuated by the treatment with MSCs.
      Consistent with the increase in portal and sinusoidal resistance in the cirrhotic
      liver, the splenic weight increased, which was again attenuated by the MSCs. The
      cells had no impact on the spontaneous improvement of liver dysfunction after
      cessation of treatment with carbon tetrachloride. However, fibrosis was
      significantly improved as assessed by image quantification of collagen stained
      with Sirius red. However, hydroxyproline was unchanged indicating that fibrillary
      collagen content was not affected. That was in line with the finding that the
      activation of hepatic stellate cells, mainly contributing to excess collagen
      production in liver cirrhosis, was not affected by the MSCs. The expression of
      metalloproteinases and their inhibitors did also not change. DISCUSSION: It is
      suggested that hepatocytic differentiated MSCs improved portal blood flow in the
      cirrhotic liver rather by the physical reestablishment of liver architecture than
      by biochemical repair.

PMID- 29074335
TI  - Choices and Decisions in Decompressive Surgery for Thoracolumbar Intervertebral
      Disk Herniation.
AB  - Once decompressive surgery has been elected, the approach that maximizes the
      likelihood of gaining access to the herniated material for complete removal
      should be chosen. In most cases, a procedure that optimizes access to the
      ventrolateral aspect of the spinal cord will be advantageous but it is important
      to tailor the details of the surgical procedure to suit individual patients.
      Decompressive surgery for chronic (type II) herniations will frequently demand a
      ventral approach with partial corpectomy.

PMID- 29074336
TI  - The Role of Fenestration in Management of Type I Thoracolumbar Disk Degeneration.
AB  - Fenestration offers the advantages of prophylaxis without the need for
      specialized instrumentation and imaging. Currently there is a lack of equipoise
      regarding the efficacy of fenestration relative to decompression for treatment of
      acute canine intervertebral disk herniation; most veterinary spinal surgeons do
      not consider the 2 procedures equivalently efficacious. Therapeutic fenestration
      should perhaps be given greater consideration, especially if advanced imaging
      shows only mild to moderate spinal cord compression or there are restrictions on
      the duration of surgery, when it might be better to spend the time on
      fenestration rather than decompression.

PMID- 29074334
TI  - Robotically Assisted Long Bone Biopsy Under MRI Imaging: Workflow and Preclinical
      Study.
AB  - RATIONALE AND OBJECTIVES: Our research team has developed a magnetic resonance
      imaging (MRI)-compatible robot for long bone biopsy. The robot is intended to
      enable a new workflow for bone biopsy in pediatrics under MRI imaging. Our long
      term objectives are to minimize trauma and eliminate radiation exposure when
      diagnosing children with bone cancers and bone infections. This article presents
      our robotic systems, phantom accuracy studies, and workflow analysis. MATERIALS
      AND METHODS: This section describes several aspects of our work including the
      envisioned clinical workflow, the MRI-compatible robot, and the experimental
      setup. The workflow consists of five steps and is intended to enable the entire
      procedure to be completed in the MRI suite. The MRI-compatible robot is MR Safe,
      has 3 degrees of freedom, and a remote center of motion mechanism for orienting a
      needle guide. The accuracy study was done in a Siemens Aera 1.5T scanner with a
      long bone phantom. Four targeting holes were drilled in the phantom. RESULTS:
      Each target was approached twice at slightly oblique angles using the robot
      needle guide for a total of eight attempts. A workflow analysis showed the
      average time for each targeting attempt was 32 minutes, including robot setup
      time. The average 3D targeting error was 1.39 mm with a standard deviation of
      0.40 mm. All of the targets were successfully reached. CONCLUSION: The results
      showed the ability of the robotic system in assisting the radiologist to
      precisely target a bone phantom in the MRI environment. The robot system has
      several potential advantages for clinical application, including the ability to
      work at the MRI isocenter and serve as a steady and precise guide.

PMID- 29074337
TI  - Fluoroquinolones and the Risk of Achilles Tendon Disorders: Update on a Neglected
      Complication.
AB  - OBJECTIVE: To evaluate the current evidence and to identify associated risk
      factors that increase the incidence of this complication. Fluoroquinolone (FQ)
      has been considered the first-line therapy for uncomplicated urinary infections.
      FQ has been associated with Achilles tendon disorders, especially during the
      first month of treatment. METHODS: Data sources searched included PubMed,
      MEDLINE, and Scopus from January 1988 to June 2017. RESULTS: A total of 79
      articles were used, with ciprofloxacin representing the most common drug.
      CONCLUSION: We found that male gender, advanced age, normal body mass index,
      chronic renal failure, and concurrent use of corticosteroids increase the risk of
      Achilles tendon disorders.

PMID- 29074338
TI  - [18F] FDG PET/CT may be a useful adjunct in diagnosis of eosinophilic fasciitis.

PMID- 29074339
TI  - Effect of Deep Brain Stimulation of the ventromedial prefrontal cortex on the
      noradrenergic system in rats.
AB  - BACKGROUND: Deep Brain Stimulation (DBS) of the subgenual cingulate cortex (SCC)
      is a promising therapeutic alternative to treat resistant major depressive
      disorder. In preclinical studies, DBS of the ventromedial prefrontal cortex
      (vmPFC, the rodent SCC correlate) provokes an antidepressant-like effect, along
      with changes in noradrenaline levels at the site of stimulation. Hence, DBS
      appears to activate the noradrenergic-locus coeruleus (LC) system.
      OBJECTIVE/HYPOTHESIS: The aim of this study was to evaluate the effect of vmPFC
      DBS on the electrical activity of noradrenergic LC neurons, cortical oscillations
      and coherence between both brain areas in male rats. METHODS: The antidepressant
      like effect of vmPFC DBS was evaluated through the forced swimming test. Tonic
      and evoked activity of LC neurons, LC activity of alpha2-adrenoceptors, local
      field potentials from LC and electrocorticogram signals were studied after DBS by
      electrophysiological recordings in anaesthetized rats. The effect of DBS on
      tyrosine hydroxylase (TH), noradrenaline transporters (NAT), phosphorylation of
      the extracellular signal-regulated kinase (ERK) and corticotropin releasing
      factor (CRF) expression in the LC were measured by western blot assays. RESULTS:
      DBS induced an antidepressant-like effect increasing climbing behaviour in the
      FST that was accompanied by a robust increase of TH expression in the rat LC. The
      tonic and evoked activity of LC neurons was enhanced by DBS, which impaired
      alpha2-adrenoceptors activity. DBS also promoted an increase in slow LC
      oscillations, as well as a shift in LC-cortical coherence. CONCLUSION: DBS of the
      vmPFC appears to affect the LC, producing changes that may underlie its
      antidepressant-like effects.

PMID- 29074340
TI  - Evaluation of clinical teaching quality in competency-based residency training in
      Lithuania.
AB  - BACKGROUND AND AIM: In 2013, all residency programs at the Lithuanian University
      of Health Sciences were renewed into the competency-based medical education
      curriculum (CBME). In 2015, we implemented the validated EFFECT questionnaire
      together with the EFFECT-System for quality assessment of clinical teaching in
      residency training. The aim of this study was to investigate the influence of
      characteristics of the resident (year of training) and clinical teacher (gender,
      age, and type of academic position) on teaching quality, as well as to assess
      areas for teaching quality improvement. MATERIALS AND METHODS: Residents from 7
      different residency study programs filled out 333 EFFECT questionnaires
      evaluating 146 clinical teachers. We received 143 self-evaluations of clinical
      teachers using the same questionnaire. Items were scored on a 6-point Likert
      scale. Main outcome measures were residents' mean overall (MOS), mean subdomain
      (MSS) and clinical teachers' self-evaluation scores. The overall comparisons of
      MOS and MSS across study groups and subgroups were done using Student's t test
      and ANOVA for trend. The intraclass correlation coefficient (ICC) was calculated
      in order to see how residents' evaluations match with self-evaluations for every
      particular teacher. To indicate areas for quality improvement items were analyzed
      subtracting their mean score from the respective (sub)domain score. RESULTS: MOS
      for domains of "role modeling", "task allocation", "feedback", "teaching
      methodology" and "assessment" valued by residents were significantly higher than
      those valued by teachers (P<0.01). Teachers who filled out self-evaluation
      questionnaires were rated significantly higher by residents in role modeling
      subdomains (P<0.05). Male teachers in (sub)domains "role modeling: CanMEDS roles
      and reflection", "task allocation", "planning" and "personal support" were rated
      significantly higher than the female teachers (P<0.05). Teachers aged 40 years or
      younger were rated higher (P<0.01). Residents ratings by type of teachers'
      academic position almost in all (sub)domains differed significantly (P<0.05). No
      correlation observed between MOS of a particular teacher and MOS as rated by
      residents (ICC=0.055, P=0.399). The main areas for improvement were "feedback"
      and "assessment". CONCLUSIONS: Resident evaluations of clinical teachers are
      influenced by teachers' age, gender, year of residency training, type of
      teachers' academic position and whether or not a clinical teacher performed self
      evaluation. Development of CBME should be focused on the continuous evaluation of
      quality, clinical teachers educational support and the implementation of e
      portfolio.

PMID- 29074341
TI  - The clinical significance of endocardial endothelial dysfunction.
AB  - Endocardial endothelium (EE) is essential in the embryonic development of the
      heart, the optimal contractility and rhythm as well as the remodeling of the
      heart. Endocardial endothelium affect the contractility of cardiomyocytes through
      paracrine signaling substances such as nitric oxide (NO), endothelin (ET-1),
      prostaglandins (PGI2, PGF2, PGE2) and angiotensin II (ANG II). Typical lesions of
      endocardial endothelium have been described in atrial fibrillation,
      ischemia/reperfusion injury, cardiac hypertrophy, heart failure, sepsis,
      myocardial infarction, inflammation and thrombosis. In patients with atrial
      fibrillation, there can be a systemic endothelial dysfunction that combines
      endocardial and vascular endothelial dysfunction and leads to increased
      hemodynamic load of the left atrium and increased synthesis and release of
      natriuretic peptides, angiotensin II, aldosterone and growth factors from the
      atrial myocardium. A dysfunction of endothelial cells in the local inflammatory
      status can lead to increased plaque vulnerability, which contributes to plaque
      rupture and favors the formation of thrombus. Preserving the endocardial
      myocardial integrity plays a significant role in the prevention of a coronary
      artery disease. Endocardial endothelial dysfunction is, similarly to coronary
      endothelial dysfunction, an early event that leads to the progression of heart
      failure. Multimarker strategy, that would include a different set of biomarkers,
      could significantly help in the assessment of patients with cardiovascular
      diseases. The challenge lays in finding new therapeutic strategies that would, by
      preserving endothelial function, prevent the onset of cardiovascular diseases.

PMID- 29074343
TI  - Different doses of sevoflurane facilitate and impair learning and memory function
      through activation of the ERK pathway and synthesis of ARC protein in the rat
      hippocampus.
AB  - BACKGROUND: Sevoflurane has been shown to stimulate or depress memory in adult
      rats; however, the cellular mechanism of this bidirectional effect has not been
      fully investigated. METHODS: We used an intra-hippocampal microinfusion of U0126
      to suppress ERK activation. Male SD rats were randomly assigned to four groups:
      Sham, 0.11%SEV, 0.3%SEV and 0.3%+U0126. They received bilateral injections of
      U0126 or saline. Rats were anesthetized, and Inhibitory Avoidance (IA) training
      was performed immediately after anesthesia. The memory retention latency was
      observed 24 h later. In another experiment, the hippocampus was removed 45 min
      after IA training to assess ARC expression, the synapsin 1 protein levels and the
      phosphorylation level of ERK. RESULTS: Treatment with 0.11%SEV led to rapid
      phosphorylation of ERK, while 0.3%SEV inhibited phosphorylation; the latter
      change was reversed by the microinfusion of U0126 in the hippocampus. The memory
      latency result had similar tendencies. The local infusion of U0126 abolished the
      0.3%SEV-induced memory impairment and ERK inhibition. Selective upregulations of
      ARC and synapsin 1 proteins were observed in the 0.3%SEV group compared with the
      0.11%SEV group. CONCLUSIONS: The results indicate that different doses of
      sevoflurane trigger synaptic plasticity-related cytoskeleton proteins through the
      ERK signaling pathway. This novel modulation by inhalational agents may help to
      reduce their side-effects on memory function.

PMID- 29074342
TI  - The use of endoscopic-assisted burr-hole craniostomy for septated chronic
      subdural haematoma: A retrospective cohort comparison study.
AB  - OBJECTIVE: To complete a retrospective comparison of endoscope-assisted burr-hole
      craniostomy (EBHC) and ordinary burr-hole craniostomy (OBHC) in the treatment of
      septated chronic subdural hematoma (SCSH). METHODS: A retrospective case note
      review comparing EBHC and OBHC of SCSH was therefore performed. Data of patients
      with a SCSH for EBHC or OBHC during the period from January 2011 to December 2016
      were retrospectively collected and analysed. Of 73 patients, 42 underwent EBHC
      and 31 patients were treated by OBHC. The primary outcome measure was recurrence
      rate and secondary outcome measures were clinical outcome at first postoperative
      day, discharge and 6 months, the length of hospital stay for neurosurgery, the
      operative time, and the placement time of drainage tube. RESULT: The rate of
      recurrence was significantly lower in the EBHC (0/42 0%) than in the OBHC (8/31,
      25.8%) group (p = .0030). The rate of morbidity was significantly lower in the
      EBHC (2/42, 4.8%) than in the OBHC (11/31, 35.5%) group (p = .0121). At 30 days,
      mortality did not differ between groups. Significantly more patients treated with
      EBHC were alive at 6 months than were those with OBHC. No patient died as a
      consequence of the operative procedure in the both groups. A discharge GCS of 15
      was recorded in more participants with EBHC than in those with OBHC. Gross
      neurological deficit was significantly less frequent in those with EBHC than in
      those with OBHC at first postoperative day and discharge, but did not differ at 6
      month follow-up. The mean placement time of drainage tube was significantly less
      in those with EBHC (27.2 h) than in those with OBHC (52.0 h, p = .0055). The mean
      length of hospital stay for neurosurgery was 4 days in the EBHC group, while it
      was 5 days in the OBHC group (p = .0015). The mean hematoma reduction rate was
      significantly higher in those with EBHC than in those with OBHC at first
      postoperative day (85.3% vs 72.5%, p = .0037) and discharge (90.3% vs 85.1%, p =
      .0127). CONCLUSION: Comparing two minimally invasive procedure protocols for
      treatment of SCSH, EBHC is a safe and effective surgical technique. It
      significantly surpasses the results obtained in OBHC in lowering recurrence rate,
      morbidity rate, placement time of drainage tube, and length of hospital stay for
      neurosurgery. We recommend EBHC technique to be widely used in the treatment of
      SCSH, even common chronic subdural hematoma (CSH), subacute and acute subdural
      hematomas, acute epidural hematomas and empyemas to avoid large craniotomies,
      particularly in elderly patients, so that patients can receive the best treatment
      on the basis of minimal trauma.

PMID- 29074344
TI  - A comparison of game-play characteristics between elite youth and senior
      Australian National Rugby League competitions.
AB  - OBJECTIVES: To compare game-play characteristics between elite youth and senior
      Australian National Rugby League (NRL) competitions. DESIGN: Longitudinal
      observational. METHODS: The dataset consisted of 12 team performance indicators
      (e.g., 'all runs', 'offloads' and 'tackles') extracted from all 2016 national
      under 20 (U20) competition (elite youth; n=372 observations) and National Rugby
      League (NRL) (elite senior; n=378 observations) matches. Data was classified
      according to competition (Two levels: U20 and NRL) and modelled using two
      techniques. Firstly, non-metric multidimensional scaling resolved multivariate
      competition (dis)similarity, visualised using a two-dimensional ordination.
      Secondly, a conditional interference (CI) classification tree was grown to reveal
      the performance indicators most capable of explaining competition level. RESULTS:
      Non-metric multidimensional scaling revealed high competition dissimilarity, with
      U20 and NRL teams orienting distinctive positions on the first dimension of the
      ordination surface. Five team performance indicators were retained within the CI
      tree ('all runs', 'tackle breaks', 'tackles', 'missed tackles', and 'kicks'),
      which correctly classified 79% of the U20 observations and 93% of the NRL
      observations. CONCLUSIONS: Multivariate differences between elite youth and
      senior rugby league competitions were identified. Specifically, NRL game-play was
      classified by a greater number of 'all runs', and 'tackles' and a lower number of
      'missed tackles' relative to the U20 competition. Given the national U20
      competition is purported to assist with the development of prospective NRL
      players, junior coaches may consider training interventions that primarily aid
      the tackling capacities of players. This may subsequently assist with talent
      development and player progression in Australian rugby league.

PMID- 29074346
TI  - An embryonic 100MUg/L lead exposure results in sex-specific expression changes in
      genes associated with the neurological system in female or cancer in male adult
      zebrafish brains.
AB  - Developmental lead (Pb) exposure is linked to neurological health issues. Results
      from non-human primate and rodent studies suggest detrimental effects of an early
      life Pb exposure, showing transcriptional disturbances and pathological evidence
      of Alzheimer's disease in the adult animal brain. To elucidate the impacts of an
      embryonic Pb exposure on the adult brain, transcriptomic analysis was completed
      on the brain of zebrafish aged 12months exposed to a control treatment or to an
      embryonic 100MUg/L Pb exposure by sex. In the adult female zebrafish brain,
      significant changes in expression profiles occurred in a number of genes involved
      in neurological disease and nervous system development and function. On the other
      hand, in adult males, a number of genes with significant expression alterations
      were found to be associated with cancer and tumors. p38 mitogen-activated protein
      kinase (p38 MAPK) was also indicated as an upstream regulator of observed gene
      expression changes. Western blot analysis confirmed activation of p38 MAPK in the
      form of phosphorylated p38 MAPK in the male zebrafish brain. In addition, we
      compared transcriptomic changes observed in this study to a previous study with
      an embryonic exposure of 10MUg/L Pb by sex, showing unique sets of genes
      dependent on Pb concentration. Overall, these results show sex-specific and
      concentration-dependent disturbances of global gene expression patterns in the
      brain of adult zebrafish exposed to Pb during embryogenesis.

PMID- 29074345
TI  - Effects of a hip brace on biomechanics and pain in people with femoroacetabular
      impingement.
AB  - OBJECTIVES: This study evaluates whether hip bracing in patients with
      femoroacetabular impingement (FAI) (a) immediately reduces range of hip internal
      rotation, flexion, adduction, and pain during functional tasks; and (b) improves
      patient-reported outcomes when worn daily over 4 weeks. DESIGN: Within
      participant design followed by a case series. METHODS: Twenty-five adults with
      symptomatic FAI underwent 3D kinematic assessment with and without a hip brace
      during single-leg squat, double-leg squat, stair ascent, and stair descent. A
      subset of this population (n=17) continued to wear the brace daily for 4-weeks. A
      linear mixed statistical model was used to assess pain and kinematic differences
      between the braced and unbraced conditions at baseline testing. Patient-reported
      outcomes (NRS pain, iHot-33 and HAGOS questionnaires) at 4-weeks were compared to
      baseline using paired t-tests. RESULTS: Bracing resulted in significant but small
      reductions in peak hip flexion ranging between 5.3 degrees  (95% CI 0.8 degrees 
      9.7 degrees ) and 5.6 degrees  (95% CI 1.1 degrees -10.0 degrees ), internal
      rotation ranging between 2.5 degrees  (95% CI 0.6 degrees -4.4 degrees ) and 6.4
      degrees  (95% CI 4.5 degrees -8.2 degrees ), and adduction ranging between 2.2
      degrees  (95% CI 0.5 degrees -3.8 degrees ) and 3.3 degrees  (95% CI 1.6 degrees 
      5.0 degrees ) during all tasks, except flexion during single-leg squat, compared
      with the unbraced condition; pain was not significantly improved with the brace.
      Bracing over four weeks did not significantly change patient-reported outcomes.
      CONCLUSIONS: Bracing subtly limited impinging hip movements during functional
      tasks, but did not immediately reduce pain or improve patient-reported clinical
      outcomes after 4 weeks in a young adult cohort with long-standing FAI.

PMID- 29074348
TI  - Development of a safe and scalable route towards a tau PET tracer precursor.
AB  - A scalable 5-step synthesis of the diazacarbazole derivative 1 used as tau PET
      tracer precursor is reported. Key features of this synthesis include a Buchwald
      Hartwig amination, a Pd catalyzed CH activation and a Suzuki-Miyaura cross
      coupling.

PMID- 29074349
TI  - Structure optimization of tetrahydropyridoindole-based aldose reductase
      inhibitors improved their efficacy and selectivity.
AB  - In our previous study, tetrahydropyridoindoles carboxymethylated in position 8
      were identified as aldose reductase (ALR2) inhibitors with mild efficacy and
      selectivity yet with significant antioxidant activity. In the present study we
      proceeded with optimization of the tetrahydropyridoindole scaffold by shifting
      the carboxymethyl pharmacophore from position 8 to position 5, with the aim to
      improve the biological activity. Commercial databases were screened for the
      presence of tetrahydropyridoindoles carboxymethylated in position 5 and an
      experimental set of eight compounds was created. Mild inhibition characterized by
      IC50 in micromolar range was recorded for compound 8 with the isopropyl
      substituent at the piperidine nitrogen (position 2). This alkylated tertiary
      nitrogen is characterized by a rather high basicity (pKa ~ 10.4) with complete
      protonization at physiological pH. On the other hand, ALR2 inhibition activity of
      the low basicity derivatives 3-7 with an acyl substituted nitrogen in position 2
      (pKa ~ -1 to -3) was characterized with IC50 values in low and medium nanomolar
      region. Docking into the binding site of human recombinant enzyme AKR1B1
      performed for 3 revealed an interaction network responsible for the high affinity
      and selectivity. In ex vivo experiment, sorbitol accumulation in isolated rat eye
      lenses was significantly inhibited by 3 in the presence of high glucose, starting
      at a concentration as low as 0.1 MUM. Moreover, in streptozotocin-induced
      diabetic rats, compound 3 administered intragastrically (i.g., 50 mg/kg/day) for
      five consecutive days significantly inhibited sorbitol accumulation in red blood
      cells and the sciatic nerve. Molecular obesity indices predicted along with water
      solubility point an excellent "lead-likeness" of compound 3, with prospects of
      further structure optimizations.

PMID- 29074347
TI  - Management consensus guideline for hepatocellular carcinoma: 2016 updated by the
      Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer
      related mortality in Taiwan. To help clinical physicians to manage patients with
      HCC, the Taiwan Liver Cancer Association and the Gastroenterological Society of
      Taiwan produced the management consensus guideline for HCC. METHODS: The
      recommendations focus on nine important issues on management of HCC, including
      surveillance, diagnosis, staging, surgery, local ablation, transarterial
      chemoembolization/transarterial radioembolization/hepatic arterial infusion
      chemotherapy, systemic therapy, radiotherapy, and prevention. RESULTS: The
      consensus statements were discussed, debated and got consensus in each expert
      team. And then the statements were sent to all of the experts for further
      discussion and refinement. Finally, all of the experts were invited to vote for
      the statements, including the level of evidence and recommendation. CONCLUSION:
      With the development of the management consensus guideline, HCC patients could
      benefit from the optimal therapeutic modality.

PMID- 29074350
TI  - Effects of charge and hydrophobicity on the oligomerization of peptides derived
      from IAPP.
AB  - Changes in pH resulting in modifications of charge can dramatically alter the
      folding and interaction of proteins. This article probes the effects of charge
      and hydrophobicity on the oligomerization of macrocyclic beta-sheet peptides
      derived from residues 11-17 of IAPP (RLANFLV). Previous studies have shown that a
      macrocyclic beta-sheet peptide containing this IAPP sequence (peptide 1Arg) does
      not form oligomers in aqueous solution at low millimolar concentrations.
      Replacing arginine with the uncharged isostere citrulline generates a homologue
      (peptide 1Cit) that forms a tetramer consisting of a sandwich of hydrogen-bonded
      dimers. The current study probes the role of charge and hydrophobicity by
      changing residue 11 to glutamic acid (peptide 1Glu) and leucine (peptide 1Leu).
      Diffusion-ordered spectroscopy (DOSY) studies show that peptides 1Glu and 1Leu
      form tetramers in solution. NOESY studies confirm that both peptides form the
      same sandwich-like tetramer as peptide 1Cit. 1H NMR spectroscopy at various
      concentrations reveals that peptide 1Leu has the highest propensity to form
      tetramers. The effects of pH and charge on oligomerization are further probed by
      incorporating histidine at position 11 (peptide 1His). DOSY studies show that
      peptide 1His forms a tetramer at high pH. At low pH, peptide 1His forms a new
      species that has not been previously observed by our research group-a dimer.
      These studies demonstrate the importance of charge and hydrophobicity in the
      oligomerization of IAPP-derived peptides.

PMID- 29074351
TI  - Prospective evaluation of urinary incontinence in severely obese adolescents
      presenting for weight loss surgery.
AB  - BACKGROUND: Obesity has been associated with daytime urinary incontinence (UI),
      likely due to increased intra-abdominal pressure. OBJECTIVES: To assess
      incontinence symptoms in severely obese adolescents before and 3 years after
      bariatric surgery. SETTING: Tertiary care pediatric hospitals in the United
      States. METHODS: The Teen-Longitudinal Assessment of Bariatric Surgery is a
      prospective, multicenter study designed to evaluate efficacy and safety of
      bariatric surgery in adolescents. Patients<19 years of age undergoing bariatric
      surgery at 5 centers between 2007 and 2012 were enrolled. Trained study staff
      collected baseline and postoperative anthropometric and clinical data. Presence
      and severity of UI were determined by standardized interview. RESULTS: A total of
      242 patients (76% female) were evaluated at baseline. The mean age was 17.1 years
      at baseline, and 72% were of white race. The preoperative median body mass index
      was 50.5 kg/m2. At baseline, 18% of females and 7% of males reported UI.
      Prediction analysis at baseline indicated that females, white race, and
      increasing body mass index had greater odds for UI. UI prevalence in females and
      males decreased to 7% and 0%, respectively, at 6 months after surgery (P<.01) and
      remained stable out to 36 months postoperatively. Furthermore, older patients
      were less likely to achieve 3-year UI remission or improvement. CONCLUSIONS: In
      adolescents undergoing bariatric surgery, UI was more common in females than in
      males. Incontinence status significantly improved by 6 months and was durable to
      3 years after surgery, suggesting that bariatric surgery favorably affects
      anatomic or physiologic mechanisms of bladder control in both males and females.

PMID- 29074352
TI  - [Safety and efficacy of intravenous tranexamic acid in endoscopic transurethral
      resections in urology: Prospective randomized trial].
AB  - BACKGROUND: Endoscopic urological procedures (transurethral resection of the
      prostate TURP/transurethral resection of bladder tumor TURBT) are not without
      risk of significant bleeding. This risk is due to the vascular nature of the
      tissues and their high levels of fibrinolytic enzymes in the tissues and urine.
      This study was conducted to evaluate the safety and efficacy of the
      antifibrinolytic agent tranexamic acid (TXA) in reducing blood loss in patients
      undergoing TURP/TURBT and transfusion requirement. METHODS: This study was a
      prospective, randomized, double-blind, placebo controlled clinical trial. One
      hundred and thirty-one patients of ASA physical status I or II, undergoing TURP
      (60 patients) or TURBT (71 patients) were randomly allocated to receive IV TXA:
      bolus of 10mg/kg at the induction of anesthesia followed by infusion of 1mg/kg/h
      intraoperatively and for 24h postoperatively or an equal volume of saline
      (control group). Blood loss was evaluated in terms of reduction in the serum
      hemoglobin level (delta Hb=Hb H24-Hb H0). RESULTS: There was no difference
      between two groups in terms of transfusion requirements and episodes of
      retention. TXA did not significantly reduce mean blood loss compared with placebo
      during TURP (1.37+/-0.69 vs. 1.72+/-1.23g/dL respectively, P=0.256) or TURBT
      (1.15+/-0.95 vs. 1.07+/-0.88g/dL; P=0.532). No thrombotic complications were
      noted in any patient. CONCLUSION: Tranexamic acid did not reduce transfusion
      requirements or perioperative blood loss in transurethral resection of the
      prostate or bladder tumor. LEVEL OF EVIDENCE: 4.

PMID- 29074353
TI  - Clinical Features of Regorafenib-induced Liver Injury in Japanese Patients From
      Postmarketing Experience.
AB  - BACKGROUND: Regorafenib (Stivarga) is an oral multikinase inhibitor currently
      approved for patients with metastatic colorectal cancer or gastrointestinal
      stromal tumor. Although hepatotoxicity has been a known product profile feature
      of regorafenib since its initial approval, its clinical features are limited to
      those found in the clinical trials. PATIENTS AND METHODS: The present study was
      conducted in 2 analysis sets: a safety analysis set for metastatic colorectal
      cancer from solicited postmarketing surveillance (PMS) in Japan (n = 1227) and an
      analysis set for serious hepatic adverse drug reactions (n = 210) from all
      patients registered for regorafenib use. RESULTS: The features of liver injury
      compatible with current product labeling included the second cycle as the most
      frequently observed time to onset, hepatocellular type as the typical pattern of
      liver injury, idiosyncratic occurrence as the possible mechanism, and rare fatal
      outcomes (0.33%; 4 of 1227). In addition to the known features, the present study
      found unpredictability in the outcome of hepatic events using the onset values of
      liver chemistry tests and delayed improvement of hepatic parameters after drug
      withdrawal. Owing to multiple confounding factors in patients with advanced
      cancer, difficulty remains in the interpretation of exploration for background
      factors and evaluation using Hy's law in oncology products. CONCLUSION:
      Regorafenib-induced liver injury can be considered idiosyncratic and typically of
      hepatocellular type, with fatal outcomes rare. Early recognition and timely drug
      withdrawal are the most important strategies to prevent progression to severe
      outcomes. At occurrence, careful observation until improvement and monitoring for
      fulminant hepatic failure are also essential.

PMID- 29074354
TI  - Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III
      Across European Countries: Variations and Outcomes.
AB  - BACKGROUND: Neoadjuvant therapy improves survival of patients with clinical stage
      II and III rectal cancer in clinical trials. In this study, we investigated the
      administration of neoadjuvant radiotherapy (neo-RT) and neoadjuvant
      chemoradiotherapy (neo-CRT) and its association with survival in resected
      patients in 2 European countries (The Netherlands and Sweden) and at 3 specialist
      centers. MATERIALS AND METHODS: Administration of neoadjuvant treatment (all
      registries) and overall survival after surgery in The Netherlands and Sweden were
      assessed. Hazard ratios (HRs) were obtained using Cox regression adjusted for
      potential confounders. RESULTS: A total of 16,095 rectal cancer patients with
      clinical stage II and III were eligible for analyses. Large variations in
      administration of neo-RT and neo-CRT were observed. Elderly patients less often
      received neo-RT and neo-CRT. Patients with stage III disease received neo-CRT
      more frequently than neo-RT. Administration of neo-RT versus surgery without
      neoadjuvant treatment was significantly associated with improved survival in The
      Netherlands (HR, 0.62; 95% confidence interval [CI], 0.53-0.73) as well as in
      Sweden (HR, 0.79; 95% CI, 0.69-0.90). Administration of neo-CRT was associated
      with enhanced survival in The Netherlands (HR, 0.62; 95% CI, 0.50-0.78) but not
      in Sweden (HR, 0.97; 95% CI, 0.80-1.18). The mortality of patients treated with
      neo-CRT compared with neo-RT showed inconsistent results in population-based
      centers. CONCLUSIONS: Our results support an association of neo-RT with enhanced
      survival among stage II and III rectal cancer patients. Comparing neo-CRT with
      neo-RT, larger variations and inconsistent results with respect to survival were
      observed across centers.

PMID- 29074355
TI  - Maximization of viability time in a mathematical model of cancer therapy.
AB  - In this paper, we study a dynamic optimization problem for a general nonlinear
      mathematical model for therapy of a lethal form of cancer. The model describes
      how the populations of cancer and normal cells evolve under the influence of the
      concentrations of nutrients (oxygen, glucose, etc.) and the applied therapeutic
      agent (drug). Regulated intensity of the therapy is interpreted as a time
      dependent control strategy. The therapy (control) goal is to maximize the
      viability time, i. e., the duration of staying in a so-called safety region
      (which specifies safe living conditions of a patient in terms of constraints on
      the amounts of cancer and normal cells), subject to limited resources of the
      therapeutic agent. In a specific benchmark case, a novel optimality principle for
      admissible therapy strategies is established. It states that the optimal
      trajectories should finally reach a certain corner of the safety region or at
      least the upper constraint on the quantity of cancer cells. The results of
      numerical simulations appear to be in good agreement with the proposed principle.
      Typical qualitative structures of optimal treatment strategies are also obtained.
      Furthermore, important characteristics of the model are the competition
      coefficient (describing the negative influence of cancer cells on normal cells),
      the upper bound in the drug integral constraint, and the ratio between the
      therapy and damage coefficients (i. e., the ratio between the positive primary
      and negative side effects of the therapy).

PMID- 29074356
TI  - Anti gliadin antibodies (AGA IgG) related to peripheral inflammation in
      schizophrenia.
AB  - Altered immune function and inflammation are seen in schizophrenia, however,
      peripheral inflammatory markers are not consistently elevated in all people,
      suggesting inflammation may be present only in a subgroup. We measured TNF-alpha
      and IL-Ibeta in 100 people with schizophrenia or schizoaffective disorder and
      correlated these with antibodies to gliadin, a protein found in wheat, barley and
      rye that has been found to be elevated in some people with schizophrenia. We
      hypothesized that higher peripheral antigliadin antibodies (AGA IgG) would be
      associated with higher peripheral inflammation as measured by TNF-alpha and IL
      1beta. Mean log transformed values of TNF-alpha, (p=.029) and IL-1beta (p=.016)
      were over twofold higher in people with schizophrenia who had high levels of AGA
      IgG (>=7 U) compared to those who did not have positivity to AGA IgG. We found a
      significant positive correlation between AGA IgG and the log transformed TNF
      alpha (r=0.42, p<.0001) as well as IL-Ibeta (r=0.51, p<.0001). The relationship
      was independent of cigarette smoking, body mass index and antipsychotic
      medications. People with schizophrenia having higher levels of AGA IgG show
      higher levels of peripheral inflammation and may define a subgroup with distinct
      pathophysiology and potentially novel treatment targets.

PMID- 29074357
TI  - Brewer's yeast is a potent inducer of fever, sickness behavior and inflammation
      within the brain.
AB  - Brewer's yeast, derived from the yeast species Saccharomyces cerevisiae (S.
      cerevisiae), is commonly used for inducing pyrexia in pharmacological studies
      screening antipyretics in rats. Despite its widespread use, the peripheral and
      central inflammatory response associated with Brewer's yeast-induced fever and
      sickness behavior in rats has not been investigated. Thus, we injected male
      Sprague-Dawley rats (150-200 g) subcutaneously with a high (4 g/kg, n = 9),
      medium (2 g/kg, n = 5) or low (0.4 g/kg, n = 6) dose of Brewer's yeast solution
      or saline (0.9%, n = 6) and measured core body temperature, cage activity, food
      intake and body mass for six days after injection. Blood and brain samples were
      collected at 2, 8, 18 and 72 h after injection; n = 5-7 per time point. Brewer's
      yeast administration dose-dependently induced fever, lethargy, anorexia and body
      mass stunting that was accompanied by increased blood plasma levels of
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha and activation of
      inflammatory transcription factors (nuclear factor (NF) for interleukin-6, signal
      transducer and activator of transcription (STAT)-3, and NF-kappaB)) in the
      hypothalamus and circumventricular organs. The increased activation of
      transcription factors following Brewer's yeast administration was accompanied by
      increased hypothalamic mRNA expression of TNF-alpha, IL-1beta and IL-6 and rate
      limiting enzymes for prostaglandin synthesis. Our results show that subcutaneous
      administration of S. cerevisae induces prolonged fever, anorexia and lethargy
      that is accompanied by a pronounced increase in the synthesis of pro-inflammatory
      cytokines, key prostaglandin synthesizing enzymes and transcription factors, in
      the periphery and brain.

PMID- 29074358
TI  - Inhibitory effect of silver nanoparticles on proliferation of estrogen-dependent
      MCF-7/BUS human breast cancer cells induced by butyl paraben or di-n-butyl
      phthalate.
AB  - In this study the effect of silver nanoparticles (AgNPs) on proliferation of
      estrogen receptor (ER)-positive human breast cancer MCF-7/BUS cells was assessed
      by means of in vitro assay. The cells were exposed in the absence of estrogens to
      AgNPs alone or in combination with aluminum chloride (AlCl3), butyl paraben (BPB)
      and di-n-butyl phthalate (DBPh). The results revealed that AgNPs at the non
      cytotoxic concentrations (up to 2MUg/mL) and AlCl3 (up to 500MUM) did not induce
      proliferation of MCF-7/BUS cells whereas BPB and DBPh showed strong estrogenic
      activity with the highest effect at 16MUM and 35MUM, respectively. AgNPs
      inhibited the proliferation of the cells induced by DBPh, BPB or even with 17beta
      estradiol (E2) during 6-day incubation in the absence of estrogens. ICI 182,780
      (10nM), a known estrogen receptor (ER) antagonist, induced strong inhibitory
      effect. AgNPs also decreased transcription of the estrogen-responsive pS2 and
      progesterone receptor (PGR) genes but modulated expression neither of ERalpha nor
      ERbeta in MCF-7/BUS cells exposed to BPB, DBPh or E2 for 6h. Our results indicate
      that AgNPs may inhibit growth of breast cancer cells stimulated by E2 or
      estrogenic chemicals, i.e. BPB and DBPh.

PMID- 29074359
TI  - Xanthatin triggers Chk1-mediated DNA damage response and destabilizes Cdc25C via
      lysosomal degradation in lung cancer cells.
AB  - Previous studies had shown that xanthatin, a natural xanthanolide sesquiterpene
      lactone, could induce mitotic arrest and apoptosis in non-small cell lung cancer
      (NSCLC) cells. Here, we examined whether the DNA damage response (DDR) could be a
      primary cytotoxic event underlying xanthatin-mediated anti-tumor activity. Using
      EdU incorporation assay in combination with novel imaging flow cytometry, our
      data indicated that xanthatin suppressed DNA replication, prevented cells from
      G2/M entry and increased the spot count of gammaH2AX nuclear foci. Given that
      checkpoint kinase 1 (Chk1) represents a core component in DDR-mediated cell cycle
      transition and the phosphorylation on Ser-345 is essential for kinase activation
      and function, we surprisingly found xanthatin distinctly modulated Ser-345
      phosphorylation of Chk1 in A549 and H1299 cells. Further investigation on
      Cdc25C/CDK1/CyclinB1 signaling cascade in the absence or presence of
      pharmacological DDR inhibitors showed that xanthatin directly destabilized the
      protein levels of Cdc25C, and recovery of p53 expression in p53-deficient H1299
      cells further intensified xanthatin-mediated inhibition of Cdc25C, suggesting p53
      dependent regulation of Cdc25C in a DDR machinery. Moreover, exogenous expression
      of Cdc25C was also substantially repressed by xanthatin and partially impaired
      xanthatin-induced G2 arrest. In addition, xanthatin could induce accumulation of
      ubiquitinated Cdc25C without undergoing further proteasomal degradation. However,
      an alternative lysosomal proteolysis of Cdc25C was observed. Interestingly,
      lysosome-like vesicles were produced upon xanthatin treatment, accompanied by
      rapid accumulation of lysosomal associated membrane protein LAPM-1. Furthermore,
      vacuolar proton (V)-ATPases inhibitor bafilomycin A1 and lysosomal proteases
      inhibitor leupeptin could remarkably overturn the levels of Cdc25C in xanthatin
      treated H1299 cells. Altogether, these data provide insight into how xanthatin
      can be effectively targeted DDR molecules towards certain tumors.

PMID- 29074360
TI  - Perivitelline threads in cleavage-stage human embryos: observations using time
      lapse imaging.
AB  - Time-lapse imaging of the human preimplantation embryo in vitro has revealed a
      transient phenomenon involving the appearance of perivitelline threads, commonly
      observed at the two-cell stage. These threads span the perivitelline space,
      arising at the specific area where the cytoplasmic membrane contacts the zona
      pellucida, before any perivitelline space is formed. The threads persist as the
      cytoplasmic membrane retracts from the zona pellucida to form the first cleavage
      furrow. In this observational report, these structures and their incidence are
      described. A total of 834 time-lapse videos from IVF treatment cycles, one per
      patient, were retrospectively analysed for perivitelline threads, from pronuclear
      formation until completion of the first cell cycle. Threads were observed in
      56.4% (470/834) of embryos and varied from a single to an array spanning an area
      of the zona pellcida. A total of 91.9% (432/470) were seen to form after
      cytoplasmic membrane-zona-pellucida contact. A total of 76.4% (359/470) were
      visible at the first cleavage furrow; 77% (362/470) were associated with
      cytoplasmic fragments at the two-cell-stage. Presence or absence of threads did
      not affect embryo development. This descriptive study is limited; further
      characterization of these structures is needed to elucidate their potential role
      in early human embryo development.

PMID- 29074361
TI  - A clinical assay for reactive oxygen species - ready for primetime?
AB  - Reactive oxygen species (ROS) have been demonstrated to have damaging effects on
      human sperm function. The measurement of ROS as an adjunct to traditional semen
      analysis has clinical relevance as part of the diagnosis of male infertility. The
      assay best suited to the clinical laboratory environment for detecting ROS
      generation remains somewhat controversial. A recent report on a multicenter study
      evaluating the reduction of nitroblue tetrazolium (NBT) to formazan precipitate
      as an indirect reporter of ROS-generating activity in spermatozoa, seminal plasma
      and semen has received a critique raising questions as to the sensitivity and
      specificity of the assay for detecting ROS. The authors of the report argue in
      response that the assay has validity and yields results that are potentially
      clinically significant. This dialogue serves to (re)direct readers to the
      original article and to consider carefully the intent and potential application
      of the assay, and whether there is sufficient scientific evidence to judiciously
      support its clinical diagnostic application.

PMID- 29074362
TI  - Supplementing zinc oxide nanoparticles to cryopreservation medium minimizes the
      freeze-thaw-induced damage to spermatozoa.
AB  - The sperm DNA integrity post cryopreservation of human semen samples is one of
      the serious concerns in human infertility treatment. In the present study, the
      beneficial effects of zinc oxide nanoparticles in preserving the functional
      ability of spermatozoa was explored. Ejaculates of normozoospermic men
      cryopreserved along with Zinc oxide nanoparticles (ZnONPs) exhibited non
      significantly higher percentage of total and progressive motility in frozen
      thawed samples compared to control. The sperm chromatin damage and
      malondialdehyde (MDA) level was significantly lower in ZnONPs group (P < 0.01 and
      P < 0.05 respectively) and the spermatozoa's ability to undergo acrosome reaction
      was also unaltered. Fluorescence microscopy and High resolution transmission
      electron microscopy analysis demonstrated that the ZnONPs do not penetrate the
      membrane of spermatozoa but stay around the spermatozoa. In conclusion, the
      presence of ZnONPs during cryopreservation appears to be beneficial to the
      spermatozoa as they withstand freeze-thaw process competently better than
      control, without any adverse effect shown.

PMID- 29074363
TI  - Ultrasound-guided femoral and obturator nerves block in the psoas compartment in
      dogs: anatomical and randomized clinical study.
AB  - OBJECTIVE: To evaluate intraoperative and postoperative efficacy of ultrasound
      (US)-guided femoral (FN) and obturator (ON) nerves block, in the iliopsoas muscle
      compartment (IPM), using an in-plane technique. STUDY DESIGN: Anatomical research
      and randomized, prospective, 'blinded' clinical study. ANIMALS: Six dog cadavers
      and 20 client-owned dogs undergoing tibial plateau levelling osteotomy (TPLO)
      surgery. METHODS: In phase 1, anatomical dissections and US imaging of the IPM
      were performed to design an US-guided nerve block involving the FN and ON
      simultaneously. The technique was considered successful if new methylene blue
      solution injection (0.1 mL kg-1) stained FN-ON for >=2 cm. In phase 2, the US
      guided nerve block designed in phase 1, combined with US-guided sciatic nerve
      (ScN) block, was performed in 20 dogs undergoing TPLO surgery. Patients were
      assigned randomly to one of two treatment groups: ropivacaine 0.3% (R3, n=10) and
      ropivacaine 0.5% (R5, n=10) at a volume of 0.1 mL kg-1 for each nerve block.
      Intraoperative success rate (fentanyl requirement < 2.1 mcg kg-1 hour-1) and
      postoperative pain score [Short Form-Glasgow Composite Measure Pain Scale (SF
      GCMPS) >= 5/20] were evaluated. RESULTS: In phase 1, the US image of FN-ON was
      detected between L6 and L7. In-plane needling technique produced a staining of >4
      cm in six of six cases. No abdominal or epidural dye spread was found. In phase
      2, median fentanyl infusion rates were 0.5 (0.0-0.9) MUg kg-1 hour-1 for R3 and
      0.6 (0.0-2.2) MUg kg-1 hour-1 for R5. At 9 and 11 hours after the peripheral
      nerve blocks, an SF-GCMPS >= 5 was observed for R3 and R5, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE: The US-guided FN-ON block in the IPM, using
      an in-plane technique, combined with US-guided ScN block, provided sufficient
      analgesia to minimize the use of fentanyl during TPLO surgery. A longer
      postoperative analgesia was observed in group R5 compared with R3.

PMID- 29074364
TI  - Improving Surgical Safety and Nontechnical Skills in Variable-Resource Contexts:
      A Novel Educational Curriculum.
AB  - OBJECTIVE: A substantial proportion of adverse intraoperative events are
      attributed to failures in nontechnical skills. To strengthen these skills and
      improve surgical safety, the Non-Technical Skills for Surgeons (NOTSS) taxonomy
      was developed as a common framework. The NOTSS taxonomy was adapted for low- and
      middle-income countries, where variable resources pose a significant challenge to
      safe surgery. The NOTSS for variable-resource contexts (VRC) curriculum was
      developed and implemented in Rwanda, with the aim of enhancing knowledge and
      attitudes about nontechnical skills and promoting surgical safety. DESIGN: The
      NOTSS-VRC curriculum was developed through a rigorous process of integrating
      contextually appropriate values. It was implemented as a 1-day training course
      for surgical and anesthesia postgraduate trainees. The curriculum comprises
      lectures, videos, and group discussions. A pretraining and posttraining
      questionnaire was administered to compare knowledge and attitudes regarding
      nontechnical skills, and their potential to improve surgical safety. SETTING: The
      setting of this study was in the tertiary teaching hospital of Kigali, Rwanda.
      PARTICIPANTS: Participants were residents of the University of Kigali. A total of
      55 residents participated from general surgery (31.4%), obstetrics (25.5%),
      anesthesia (17.6%), and other surgical specialties (25.5%). RESULTS: In a paired
      analysis, understanding of NOTSS improved significantly (55.6% precourse, 80.9%
      postcourse, p<0.01). All residents reported that the course would improve their
      ability to provide safer patient care, and 97.4% believed developing nontechnical
      skills would improve patient outcomes. CONCLUSIONS: Nontechnical skills must be
      highlighted in surgical training in low- and middle-income countries. The NOTSS
      VRC curriculum can be implemented without additional technology or significant
      financial cost. Its deliberate design for resource-constrained settings allows it
      to be used both as an educational course and a quality improvement strategy. Our
      research demonstrates it is feasible to improve knowledge and attitudes about
      NOTSS through a 1-day course, and represents a novel approach to improving global
      surgical safety.

PMID- 29074365
TI  - 'Snack' versus 'meal': The impact of label and place on food intake.
AB  - Eating behaviour is influenced by both cognitions and triggers in the
      environment. The potential difference between a 'snack' and a 'meal' illustrates
      these factors and the way in which they interact, particularly in terms of the
      label used to describe food and the way it is presented. To date no research has
      specifically explored the independent and combined impact of label and
      presentation on eating behaviour. Using a preload/taste test design this
      experimental study evaluated the impact of label ('snack' vs. 'meal') and place
      ('snack' vs. 'meal') of a preload on changes in desire to eat and subsequent food
      intake. Eighty female participants consumed a pasta preload which labelled as
      either a 'snack' or a 'meal' and presented as either a 'snack' (standing and
      eating from a container) or a 'meal' (eating at a table from a plate), generating
      four conditions. The results showed main effects of label and place with
      participants consuming significantly more sweet mass (specifically chocolate) at
      the taste test when the preload had been labelled a 'snack' and more total mass
      and calories when the preload had been presented as a 'snack'. No label by place
      interactions were found. The results also showed a combined effect of both label
      and place with those who had eaten the preload both labelled and presented as a
      'snack' consuming significantly more in terms of nearly all measures of food
      intake than those in the other conditions. To conclude, label and presentation
      influence subsequent food intake both independently and combined which is
      pertinent given the increase in 'snacking' in contemporary culture.

PMID- 29074366
TI  - Production and evaluation of recombinant Burkholderia pseudomallei GroEL and OmpA
      proteins for serodiagnosis of melioidosis.
AB  - Melioidosis is a bacterial infectious disease caused by Burkholderia pseudomallei
      (B. pseudomallei). The variable clinical manifestations of this disease make its
      diagnosis difficult. The gold standard strategy for diagnosis is bacterial
      culture and identification, which is time-consuming and often too late for early
      medical intervention. Therefore, a rapid and accurate diagnosis of melioidosis is
      needed for effective treatment. This study aimed to produce and evaluate two
      purified B. pseudomallei recombinant proteins (rGroEL and rOmpA) as potential
      antigens for melioidosis diagnosis by ELISA. A total of 218 serum samples from
      Thailand was analysed. The study includes melioidosis patients' serum samples
      confirmed by bacterial culture (n=38); sera from patients with various bacterial
      infections but negative for B. pseudomallei (disease control, n=55); and sera
      from healthy individuals from non-endemic (n=77) and endemic (n=48) regions. The
      rGroEL ELISA achieved a good sensitivity of 92%, which was higher than that of
      rOmpA ELISA (76%). The specificities of rGroEL and rOmpA ELISAs were 88% and 90%,
      respectively. Both antigens demonstrated good diagnostic accuracy, at 89%
      (rGroEL) and 88% (rOmpA). There was less reactivity of sera from healthy
      individuals with rGroEL than rOmpA antigens. These data highlight the usefulness
      of rGroEL purified protein as a potential antigen for the serodiagnosis of
      melioidosis by ELISA and may be useful in the development of additional methods,
      such as dot blot ELISA or immunochromatographic tests (ICT), for a rapid, simple,
      cost-effective and efficient diagnosis for use in poorly resourced regions where
      melioidosis is endemic.

PMID- 29074367
TI  - Do cystic fibrosis centres with the lowest FEV1 still use the least amount of
      intravenous antibiotics? A registry-based comparison of intravenous antibiotic
      use among adult CF centres in the UK.
AB  - BACKGROUND: The Epidemiologic Study of Cystic Fibrosis using 1995-1996 and 2003
      2005 data found that CF centres with lowest FEV1 tended to use fewer intravenous
      antibiotics. We repeated the analyses using 2013-2014 UK CF registry data to
      determine if this was still the case. METHODS: Analysing data for 2013 and 2014
      separately, 28 adult CF centres were ranked according to median % age-adjusted
      FEV1. The top 7 centres were placed in the 'upper quarter' (best FEV1), the
      bottom 7 centres in 'lower quarter' (lowest FEV1), and the rest in 'middle half'.
      IV use was stratified according to %FEV1, then compared between the three groups.
      RESULTS: Centres in the 'upper quarter' and 'middle half' used significantly more
      IV antibiotics compared to centres in the 'lower quarter' (van Elteren test P
      value<0.001). Regression analyses showed that people with CF attending centres in
      the 'upper quarter' or 'middle half' are 30-50% more likely to receive at least
      one IV course per year compared to people attending centres in the 'lower
      quarter'. CONCLUSIONS: CF centres with lowest FEV1 are still distinguished by
      lower use of intravenous antibiotics.

PMID- 29074369
TI  - Transient Hypokalemic Quadriplegia After a Lumbar Transforaminal Epidural
      Dexamethasone Injection: A Case Report.
AB  - : A 30-year-old man with no significant medical history presented with
      hypokalemic quadriplegia 4 hours after he received a lumbar transforaminal
      epidural steroid injection (ESI) containing dexamethasone and lidocaine. A
      comprehensive workup ruled out acquired and hereditary causes of hypokalemic
      paralysis. Symptoms gradually resolved within hours after potassium restoration
      with no residual neurologic deficits. Paralysis after transforaminal ESI is
      uncommon but has been associated with particulate steroids that can coalesce into
      aggregates and occlude vessels. To our knowledge, there have been no case reports
      of paralysis after ESI with dexamethasone, a nonparticulate steroid. This
      transient paralysis is possibly caused by the effects of glucocorticoids on Na-K
      channels and insulin resistance resulting in hyperglycemia and subsequent
      hypokalemia. We reviewed the differential diagnosis of transient paralysis after
      epidural steroid injection in this report. LEVEL OF EVIDENCE: IV.

PMID- 29074368
TI  - Planctomycetes attached to algal surfaces: Insight into their genomes.
AB  - Planctomycetes are bacteria with complex molecular and cellular biology. They
      have large genomes, some over 7Mb, and complex life cycles that include motile
      cells and sessile cells. Some live on the complex biofilm of macroalgae. Factors
      governing their life in this environment were investigated at the genomic level.
      We analyzed the genomes of three planctomycetes isolated from algal surfaces. The
      genomes were 6.6Mbp to 8.1Mbp large. Genes for outer-membrane proteins,
      peptidoglycan and lipopolysaccharide biosynthesis were present. Rubripirellula
      obstinata LF1T, Roseimaritima ulvae UC8T and Mariniblastus fucicola FC18T shared
      with Rhodopirellula baltica and R. rubra SWK7 unique proteins related to metal
      binding systems, phosphate metabolism, chemotaxis, and stress response. These
      functions may contribute to their ecological success in such a complex
      environment. Exceptionally huge proteins (6000 to 10,000 amino-acids) with
      extracellular, periplasmic or membrane-associated locations were found which may
      be involved in biofilm formation or cell adhesion.

PMID- 29074370
TI  - The zinc finger protein CG12744 is essential for differentiation and regeneration
      after infection in the adult Drosophila midgut.
AB  - Pluripotent stem cell activity is essential to maintain regeneration and
      homeostasis in the Drosophila midgut following environmental challenges. Although
      multiple pathways have been implicated in epithelial renewal, the underlying
      regulatory mechanisms and correlations between relevant genes and pathways remain
      elusive. In this study, we show that the zinc finger protein CG12744 plays an
      important role in the differentiation and regeneration of epithelial cells in
      response to oral infection with Erwinia carotovora carotovora 15. Knocking down
      CG12744 in enteroblasts decreased the post-infection proportion of enteroblasts
      and enterocytes and increased the post-infection number of enteroendocrine cells.
      In addition, in precursors, CG12744 affected the Osa, jun-N-terminal kinase and
      bone morphogenetic protein signaling pathways to control enterocyte
      differentiation. Finally, CG12744 maintained epithelial architecture and cell
      fate in enterocytes following an acute infectious challenge.

PMID- 29074371
TI  - Hemoglobin pretreatment endows rat cortical astrocytes resistance to hemin
      induced toxicity via Nrf2/HO-1 pathway.
AB  - Oxidative stress mediated secondary injury contributes to neurological
      deterioration after intracerebral hemorrhage (ICH). Astrocytes, the most dominant
      cells in the central nervous system (CNS), play key roles in maintaining redox
      homeostasis by providing oxidative stress defense. Hemoglobin (Hb), the primary
      component released by hemolysis, is an effective activator of astrocytes. Hemin,
      the product of Hb degradation, is highly toxic due to the induction of reactive
      oxygen species (ROS). We speculate that Hb-activated astrocytes are resistant to
      hemin-induced toxicity. To verify our speculation, Hb-pretreated astrocytes were
      exposed to hemin, intracellular ROS accumulation and cell apoptosis were
      evaluated. Heme oxygenase 1 (HO-1) and nuclear transcription factor-erythroid 2
      related factor (Nrf2) expression were observed to explore the potential
      mechanism. The results demonstrated that Hb induced upregulation and nuclear
      translocation of Nrf2 in astrocytes, resulted in HO-1 upregulation, which
      contributed to reduced ROS accumulation and apoptosis rate. Knocking down Nrf2
      expression by siRNA suppressed Hb-induced upregulation of HO-1 expression and
      increased the susceptibility of Hb-pretreated astrocytes to hemin-induced
      toxicity. Taken together, Hb-activated astrocytes acquired resistance to hemin
      induced toxicity via Nrf2/HO-1 pathway. This phenomenon can be considered as the
      adaptive self-defense in the pathological process of ICH. Hb pre-warned
      astrocytes and enhanced their capability of handling the coming hemin "flood".
      Nrf2/HO-1 may be employed as a target for neuroprotection after ICH.

PMID- 29074372
TI  - Sequence and localization of kcnk10a in the brain of adult zebrafish (Danio
      rerio).
AB  - kcnk10a has been predicted in zebrafish to be a member of the two-pore domain
      potassium ion (K+) channel-related K+ (TREK) channel family known as a
      thermoreceptor. Since reproduction is affected by temperature, Kcnk10a could be
      involved in the regulation of reproduction. However, expression of kcnk10a in the
      zebrafish brain and association with reproduction has not been identified. In
      this study, the full length sequence and localization of kcnk10a in the brain was
      investigated and gene expressions of the TREK channel family were examined to
      investigate association with reproduction. We initially identified the full
      length cDNA sequence of kcnk10a using Rapid Amplification of cDNA Ends and
      localization in the zebrafish brain using in situ hybridization. Furthermore, we
      examined the gene expression differences of kcnk2b, kcnk10a and kcnk10b mRNA
      between genders as well as developmental stages by real-time PCR. The deduced
      amino acid sequence of the identified kcnk10a mRNA contains highly conserved two
      pore domains and four transmembrane regions and was higher similarity to
      zebrafish Kcnk10b than zebrafish Kcnk2a and 2b. kcnk10a mRNA was widely
      distributed in the brain such as the preoptic area, hypothalamus and the
      midbrain. kcnk10a mRNA expression exhibited significant difference between mature
      male and female, and increase during puberty. Kcnk10a could be involved in the
      regulation of reproductive function.

PMID- 29074373
TI  - Bone Marrow Harvest in Pediatric Sibling Donors: Role of Granulocyte Colony
      Stimulating Factor Priming and CD34+ Cell Dose.
AB  - To ensure optimal clinical outcomes for patients while retaining adequate
      protection for donors, the National Marrow Donor Program developed guidelines
      specifying that up to 20 mL/kg of bone marrow can be harvested from donors. These
      guidelines, originally developed for unrelated adult donors, are followed in
      children as well. We studied the impact of granulocyte colony-stimulating factor
      (G-CSF) priming on the cellular composition of harvested bone marrow, sought to
      develop an algorithm to optimize bone marrow harvest volume from pediatric
      matched sibling donors, and studied the impact of CD34+ cell dose on clinical
      outcomes. We analyzed data from 92 bone marrow harvests and clinical outcomes for
      69 sibling recipient-donor duos, The mean age of recipients was 9.85 +/- 5.90
      years, and that of donors was 11.85 +/- 6.36 years. G-CSF priming was not
      associated with higher yield of CD34+ cells/uL. The median CD34+ cell count
      obtained from donors was 700 cells/uL (range, 400-1700 cells/uL) in donors age <6
      years, 360 cells/uL (range, 100-1100 cells/uL) in donors age 6 to 12 years, and
      300 cells/uL (range, 80-800 cells/uL) in donors age >12 years (P < .001). The
      number of CD34+ cells infused had no impact on traditional clinical outcomes;
      however, it was significantly related to graft-versus-host
      disease/relapse/rejection-free survival. Our investigation revealed that
      ultimately, a CD34+ cell count of approximately 3 to 5 * 106/kg was a threshold
      beyond which increasing CD34+ cell dose did not impact outcome. In this study, we
      addressed the broad question of whether harvesting up to 20 mL/kg of bone marrow
      from a child donor is truly necessary for optimal outcomes in every pediatric
      case.

PMID- 29074374
TI  - C-Reactive Protein Levels at Diagnosis of Acute Graft-versus-Host Disease Predict
      Steroid-Refractory Disease, Treatment-Related Mortality, and Overall Survival
      after Allogeneic Hematopoietic Stem Cell Transplantation.
AB  - Acute graft-versus-host disease (aGVHD) remains a cause of excessive morbidity
      and mortality after allogeneic hematopoietic stem cell transplantation (HSCT).
      Primary treatment consists of high-dose corticosteroids, but a small group of
      patients develop steroid-refractory disease, and their prognosis is especially
      poor. There is experimental evidence that coexisting inflammation aggravates
      aGVHD. Because C-reactive protein (CRP) is a systemic inflammatory marker, we
      aimed to investigate whether plasma CRP concentrations at the diagnosis of aGVHD
      can predict the risk of failing first-line therapy and developing steroid
      refractory disease. We retrospectively studied 461 patients who underwent HSCT
      between 2010 and 2015. aGVHD grade II-IV was diagnosed in 148 patients (32%). CRP
      level and total white blood cell, lymphocyte, and neutrophil counts were
      available for all patients at the time of aGVHD diagnosis. According to local
      protocol, patients with failed response to high-dose steroid therapy (2 mg/kg)
      were treated with the TNF-alpha inhibitor infliximab and categorized as having
      steroid-refractory disease. Of 148 patients with grade II-IV aGVHD, 28 (19%)
      developed steroid-refractory disease. In these patients, plasma CRP concentration
      at diagnosis ranged between <1 and 253 mg/L. CRP levels were significantly higher
      in patients who developed steroid-refractory disease compared with those who
      responded to high-dose corticosteroid therapy (odds ratio, 1.50; 95% confidence
      interval, 1.18-1.93; P = .001). This translated into significantly increased
      transplantation-related mortality and decreased overall survival in the patients
      with high CRP levels. Total white blood cell, lymphocyte, and neutrophil counts
      were not associated with steroid resistance in the patients with aGVHD. These
      results suggest that CRP level at diagnosis is a valid predictor of the
      development of steroid-refractory disease in patients who develop grade II-IV
      aGVHD after HSCT.

PMID- 29074375
TI  - An Intercompany Perspective on Biopharmaceutical Drug Product Robustness Studies.
AB  - The Biophorum Development Group (BPDG) is an industry-wide consortium enabling
      networking and sharing of best practices for the development of
      biopharmaceuticals. To gain a better understanding of current industry approaches
      for establishing biopharmaceutical drug product (DP) robustness, the BPDG
      Formulation Point Share group conducted an intercompany collaboration exercise,
      which included a bench-marking survey and extensive group discussions around the
      scope, design, and execution of robustness studies. The results of this industry
      collaboration revealed several key common themes: (1) overall DP robustness is
      defined by both the formulation and the manufacturing process robustness; (2)
      robustness integrates the principles of quality by design (QbD); (3) DP
      robustness is an important factor in setting critical quality attribute control
      strategies and commercial specifications; (4) most companies employ robustness
      studies, along with prior knowledge, risk assessments, and statistics, to develop
      the DP design space; (5) studies are tailored to commercial development needs and
      the practices of each company. Three case studies further illustrate how a
      robustness study design for a biopharmaceutical DP balances experimental
      complexity, statistical power, scientific understanding, and risk assessment to
      provide the desired product and process knowledge. The BPDG-Formulation Point
      Share discusses identified industry challenges with regard to biopharmaceutical
      DP robustness and presents some recommendations for best practices.

PMID- 29074376
TI  - Industry's View on Using Quality Control, Biorelevant, and Clinically Relevant
      Dissolution Tests for Pharmaceutical Development, Registration, and
      Commercialization.
AB  - This article intends to summarize the current views of the IQ Consortium
      Dissolution Working Group, which comprises various industry companies, on the
      roles of dissolution testing throughout pharmaceutical product development,
      registration, commercialization, and beyond. Over the past 3 decades, dissolution
      testing has evolved from a routine and straightforward test as a component of end
      product release into a comprehensive set of tools that the developer can deploy
      at various stages of the product life cycle. The definitions of commonly used
      dissolution approaches, how they relate to one another and how they may be
      applied in modern drug development, and life cycle management is described in
      this article. Specifically, this article discusses the purpose, advantages, and
      limitations of quality control, biorelevant, and clinically relevant dissolution
      methods.

PMID- 29074377
TI  - Dual Therapeutic Effects of an Albumin-Based Nitric Oxide Donor on 2 Experimental
      Models of Chronic Kidney Disease.
AB  - Chronic kidney disease (CKD) is accompanied by a variety of complications,
      typically renal anemia and kidney fibrosis. Accordingly, it is desirable to
      develop the novel therapeutics that can treat these CKD conditions. Since nitric
      oxide (NO) has multiple functions including hypoxia inducible factor stabilizing,
      anti-inflammatory, anti-oxidative, and anti-apoptoic activities, the use of NO
      for the CKD therapy has attracted considerable interest. Here, we evaluate the
      therapeutic impacts of S-nitrosated human serum albumin (SNO-HSA), a long-lasting
      NO donor, on 2 animal models of CKD. SNO-HSA increased the expression of
      erythropoietin (EPO), VEGF, and eNOS by stabilizing hypoxia inducible factor
      1alpha in HepG2 and HK-2 cells. SNO-HSA increased hematopoiesis in both healthy
      and renal anemia rats, suggesting the promotion of EPO production. In unilateral
      ureteral obstruction-treated mice, SNO-HSA ameliorated kidney fibrosis by
      suppressing the accumulation of renal extracellular matrix. SNO-HSA also
      inhibited unilateral ureteral obstruction-induced alpha-smooth muscle actin
      increase and E-cadherin decrease, suggesting that SNO-HSA might suppress the
      accumulation of myofibroblasts, an important factor of fibrosis. SNO-HSA also
      inhibited the elevations of fibrosis factors, such as transforming growth factor
      beta, interleukin-6, and oxidative stress, while it increased EPO production, an
      anti-fibrosis factor. In conclusion, SNO-HSA has the potential to function as a
      dual therapeutics for renal anemia and kidney fibrosis.

PMID- 29074378
TI  - Estimating the Physicochemical Properties of Polysubstituted Aromatic Compounds
      Using UPPER.
AB  - The UPPER model (Unified Physicochemical Property Estimation Relationships) has
      been used to predict 9 essential physicochemical properties of pure compounds. It
      was developed almost 25 years ago and has been validated by the Yalkowsky group
      for almost 2000 aliphatic, aromatic, and polyhalogenated hydrocarbons. UPPER is
      based on a group of additive and nonadditive descriptors along with a series of
      well-accepted thermodynamic relationships. In this model, the 2-dimensional
      chemical structure is the only input needed. This work extends the applicability
      of UPPER to hydrogen bonding and non-hydrogen bonding aromatic compounds with
      several functional groups such as alcohol, aldehyde, ketone, carboxylic acid,
      carbonate, carbamate, amine, amide, nitrile as well as aceto, and nitro
      compounds. The total data set includes almost 3000 compounds. Aside from the
      enthalpies and entropies of melting and boiling, no training set is used for the
      calculation of the properties. The results show that UPPER enables a reasonable
      estimation of all the considered properties.

PMID- 29074379
TI  - Impacting Global Health Through Equipment Repurposing: Measurable Progress
      Through the Accumulation of Many Tiny Victories.
AB  - There is an active and growing effort occurring in laboratories throughout Africa
      to research the underpinnings of endemic communicable diseases, many of which are
      considered "neglected tropical diseases" as defined by the World Health
      Organization. Across the continent, scientists, doctors, health care workers, and
      students investigate the in vitro activity of pharmacologically active extracts
      against known pathogens in hope of discovering new treatments for the diseases
      that affect the local population. During the summer of 2014, I had the
      opportunity to visit laboratories in 3 different countries engaged in this area
      of research through participation in the Merck Fellowship for Global Health
      (Merck is known as Merck, Sharp & Dohme outside of the United States and
      Canada.), in which Merck sponsors employees on a short-term sabbatical to work
      with a global health-focused nonprofit organization. This commentary describes
      the objectives of the fellowship program, the specific project to which my co
      fellow and I contributed, and the story of a subsequent equipment donation effort
      that was inspired by my individual fellowship experience. It also captures a few
      of the more notable challenges and opportunities for the scientists in the
      laboratories we visited. Finally, for the reader who may be curious as to how she
      or he can contribute, I hope to move you to action by highlighting some of the
      opportunities for researchers to positively and creatively impact global health
      from their "home" lab benches and hoods.

PMID- 29074380
TI  - Effect of Controlled Ice Nucleation on Stability of Lactate Dehydrogenase During
      Freeze-Drying.
AB  - Several controlled ice nucleation techniques have been developed to increase the
      efficiency of the freeze-drying process as well as to improve the quality of
      pharmaceutical products. Owing to the reduction in ice surface area, these
      techniques have the potential to reduce the degradation of proteins labile during
      freezing. The objective of this study was to evaluate the effect of ice
      nucleation temperature on the in-process stability of lactate dehydrogenase
      (LDH). LDH in potassium phosphate buffer was nucleated at -4 degrees C, -8
      degrees C, and -12 degrees C using ControLyoTM or allowed to nucleate
      spontaneously. Both the enzymatic activity and tetramer recovery after freeze
      thawing linearly correlated with product ice nucleation temperature (n = 24).
      Controlled nucleation also significantly improved batch homogeneity as reflected
      by reduced inter-vial variation in activity and tetramer recovery. With the
      correlation established in the laboratory, the degradation of protein in
      manufacturing arising from ice nucleation temperature differences can be
      quantitatively predicted. The results show that controlled nucleation reduced the
      degradation of LDH during the freezing process, but this does not necessarily
      translate to vastly superior stability during the entire freeze-drying process.
      The capability of improving batch homogeneity provides potential advantages in
      scaling-up from lab to manufacturing scale.

PMID- 29074381
TI  - Drug Solubilization by Means of a Surface-Modified Edible Biopolymer Enabled by
      Hot Melt Extrusion.
AB  - A coprocessing/formulation approach for increasing the solubility of poorly
      soluble drugs using solid dispersions is presented, whereby the active
      pharmaceutical ingredients (API) retains its crystalline state. The approach uses
      a biopolymer naturally produced as dendrimeric nanoparticles that has been
      surface-modified to act as a solubilizing agent. The solubilizing agent is
      enabled by hot melt extrusion to produce the solid dispersions. Four APIs,
      phenytoin (PHT), griseofulvin, ibuprofen, and loratadine were used as model
      compounds to evaluate solubility enhancement. The rank order in solubility
      enhancement follows that of the hydrophobicity of the APIs. The APIs remained
      predominantly crystalline after hot melt extrusion processing. However, APIs with
      weak crystal structure (ibuprofen and loratadine) underwent measurable
      crystallinity loss. The solubilizing power of the modified biopolymer increases
      with increasing hydrophobicity and strength of the crystal structure. The
      solubility is described in terms of a parallel liquid-phase partition
      association. For one API (PHT), solubility enhancement was minimal. The
      dissimilar behavior of PHT is discussed in terms of the polarity match between
      the API and the hydrophobic microenvironment in the solubilizing agent. This
      approach is expected to apply to a large number of poorly soluble drugs, offering
      a complementary approach to existing processing and formulation drug
      solubilization methods.

PMID- 29074382
TI  - Relationship between Mediterranean diet and asymptomatic peripheral arterial
      disease in a population of pre-menopausal women.
AB  - BACKGROUND AND AIMS: The Mediterranean Diet (MedD) is considered a very healthy
      diet useful in the prevention of cardiovascular disease. The present study aims
      to evaluate adherence to MedD in unselected premenopausal women and its relation
      with ankle-brachial index (ABI), an index of preclinical atherosclerosis. METHODS
      AND RESULTS: A group of 425 patients (age range 45-54 years) was investigated.
      They were enrolled only if they were asymptomatic for cardiovascular disease.
      Nutritional parameters were assessed by a self-administered food frequency
      validated questionnaire (116 items) completed by an interviewer administered 24 h
      diet recall. They all underwent ABI measurement. The mean MedD Score was 32.2 +/-
      6.1 (Q1-Q3 range 26-37) comparing with data from Italian population (46 +/- 8.3)
      was significantly lower. Intake of food categories sources of antioxidants was
      higher in patients with a greater adherence to Med D and was mainly related to
      fruit and vegetables. Patients were categorized in quartile according to MedD
      Score and we evaluate the distribution of ABI index within quartile. 31.4% of
      women in Q1 (lower adherence to MedD) had an ABI lower than 0.9 compared to 18.3%
      of women in Q4 (higher adherence to MedD): p < 0.01. Obesity was more frequent in
      Q1 compared to Q4 and in women with lower ABI. CONCLUSIONS: Women with a low MedD
      Score were more obese and showed instrumental sign of preclinical peripheral
      atherosclerosis. MedD rich in antioxidants from fruit, vegetables and nuts
      influenced the development of atherosclerosis and was associated with a lower
      incidence of asymptomatic atherosclerosis.

PMID- 29074383
TI  - Association of dietary patterns with five-year degree and progression of coronary
      artery calcification in the Heinz Nixdorf Recall study.
AB  - BACKGROUND AND AIMS: As a modifiable lifestyle factor, diet is hypothesized to
      play an important role in the progression of atherosclerosis. The aim of this
      study was to explore associations of comprehensive dietary patterns derived by
      cluster analysis with degree and progression of coronary artery calcification
      (CAC) over five years of follow-up. METHODS AND RESULTS: In the population-based
      Heinz Nixdorf Recall study, 3718 participants (45-75 years; 47.6% men) without
      coronary heart disease completed a food frequency questionnaire at baseline. Five
      distinct dietary patterns were identified using cluster analysis: "Health
      conscious", "Traditional German/Less alcohol", "Mediterranean-like", "Western"
      and "Animal fat/Alcohol" (used as reference). CAC was measured using electron
      beam computed tomography at baseline and five years later. CAC after five years
      was predicted based on sex- and age-specific baseline percentiles. After
      comparing observed and predicted CAC Scores, CAC progression was classified as
      slow, expected, or rapid. Compared to "Animal fat/Alcohol" diet, a "Mediterranean
      like" diet was associated with a relative risk (RR) for a rapid CAC progression
      in both sexes (men: 0.61; 95%-confidence interval [95%-CI]: 0.41; 0.90; women:
      0.59; 95%-CI: 0.45; 0.78). Furthermore, reduced RRs were observed in women with a
      "Health-conscious" and a "Traditional German/Less alcohol" diet (0.63; 95%-CI:
      0.47; 0.84, respectively 0.69; 95%-CI: 0.52; 0.90). No association was observed
      for a "Western" diet for both sexes. Similar results were revealed for degree of
      CAC. CONCLUSION: The study results support the hypothesis that a "Mediterranean
      like" diet is associated with a lower CAC-progression and lower degree of CAC in
      men and women.

PMID- 29074384
TI  - Body composition differences between adults with multiple sclerosis and BMI
      matched controls without MS.
AB  - BACKGROUND: Persons with multiple sclerosis (MS) have many health conditions
      related to overweight and obesity, but little is known about how body composition
      among those with MS compares to those without MS at the same weight. OBJECTIVE:
      To compare differences in whole body and regional body composition between
      persons with and without MS matched for sex and body mass index (BMI). METHODS:
      Persons with MS (n = 51) and non-MS controls (n = 51) matched for sex and BMI.
      Total mass, lean mass, fat mass, and percent body fat (%BF) of total body and
      arm, leg, and trunk segments were assessed using dual-energy X-ray absorptiometry
      (DXA). RESULTS: Men with MS had significantly less whole body lean mass (mean
      difference: 9933.5 +/- 3123.1 g, p < 0.01) and higher fat mass (mean difference:
      6079.0 +/- 2137.4 g, p = .01) and %BF (mean difference: 9.43 +/- 2.04%, p < 0.01)
      than BMI-matched non-MS counterparts. Further, men with MS had significantly
      lower lean mass in the arm (p = 0.02) and leg (p < 0.01) and higher fat mass in
      the arm (p = 0.01), leg (p = 0.03) and trunk (p = 0.03) than men without MS. Men
      with MS had significantly higher %BF in all three regions (p < 0.01) than men
      without MS. There were no differences between women with and without MS.
      CONCLUSIONS: We observed significant differences in whole body and regional body
      composition between BMI-matched men with and without MS. Additional research is
      needed to further explore differences in body composition, adipose distribution,
      and the impact of these differences on the health and function of men with MS.

PMID- 29074385
TI  - How the brain connects in response to acute stress: A review at the human brain
      systems level.
AB  - The brain's response to stress is a matter of extensive neurocognitive research
      in an attempt to unravel the mechanistic underpinnings of neural adaptation. In
      line with the broadly defined concept of acute stress, a wide variety of
      induction procedures are used to mimic stress experimentally. We set out to
      review commonalities and diversities of the stress-related functional activity
      and connectivity changes of functional brain networks in healthy adults across
      procedures. The acute stress response is consistently associated with both
      increased activity and connectivity in the salience network (SN) and surprisingly
      also with increased activity in the default mode network (DMN), while most
      studies show no changes in the central executive network. These results confirm
      earlier findings of an essential, coordinating role of the SN in the acute stress
      response and indicate a dynamic role of the DMN whose function is less clear.
      Moreover, paradigm specific brain responses have to be taken into account when
      investigating the role and the within and between network connectivity of these
      three networks.

PMID- 29074386
TI  - Unlike Th1/Th17 cells, Th2/Th9 cells selectively migrate to the
      limbus/conjunctiva and initiate an eosinophilic infiltration process.
AB  - In this study we compared polarized mouse T-helper (Th) lymphocytes of four
      populations, sensitized against an ocular antigen, for their patterns of
      migration and induction of inflammatory processes in recipient mouse eyes
      expressing the target antigen. Th1, Th2, Th9 and Th17 cells transgenically
      expressing T-cell receptor (TCR) specific against hen egg lysozyme (HEL) were
      adoptively transferred to recipient mice expressing HEL in their eyes. Recipient
      eyes collected 4 or 7 days post injection were analyzed for histopathological
      changes. Th1 and Th17 cells induced moderate to severe intraocular inflammation
      in the recipient mouse eyes, but essentially did not migrate into the
      conjunctiva. In contrast, Th2 and Th9 cells invaded minimally the intraocular
      space of recipient eyes, but accumulated in the limbus and migrated into the
      conjunctiva of the recipient mice and initiated allergy-like inflammatory
      responses, as indicated by remarkable eosinophil involvement. These data thus
      shed new light on the differences between the migration patterns and ocular
      pathogenic processes mediated by Th1/Th17 and by Th2/Th9 populations.

PMID- 29074387
TI  - Ocular tissue distribution and pharmacokinetic study of a small 13kDa domain
      antibody after intravitreal, subconjuctival and eye drop administration in
      rabbits.
AB  - Domain antibodies (dAb's) comprise the smallest functional unit of human IgG and
      can be targeted to a range of different soluble cytokine and receptor targets in
      the eye. In particular their small size may offer advantage for ocular tissue
      penetration and distribution. To investigate this we used a 13kDa tool molecule
      to undertake a preliminary short term ocular tissue distribution and
      pharmacokinetic study in the rabbit eye. The dAb was administered by the
      intravitreal or subconjunctival route or, as topical eye drops for up to five
      days and dAb concentrations measured in vitreous, aqueous, conjunctiva, choroid
      RPE, retina, iris, sclera, and ciliary body. The observed elimination half-live
      of the dAb (~3 days) in vitreous showed a similar elimination rate to that of a
      much larger (~50kDa) Fab fragment whilst the half-life following subconjunctival
      administration was ~24 h and, after eye drop dosing the dAb was detectable in
      aqueous and conjunctiva. These preliminary data show that the intravitreal half
      life of dAb's are similar to much larger antibody fragments, offering the
      potential to deliver significantly more drug to target on a molar basis with a
      single intravitreal injection potentially enabling dosing frequencies of once a
      month or less. Subconjunctival injection may provide short duration therapeutic
      levels of dAb to the anterior and posterior chamber whilst topical eye drop
      delivery of dAbs may be useful in front-of-eye disease. These data indicate that
      small domain antibodies may have utility in ophthalmology. Further studies are
      warranted.

PMID- 29074388
TI  - Functional assessment of the aqueous humour distal outflow pathways in bovine
      eyes using time-of-flight magnetic resonance tomography.
AB  - The major part of the aqueous humor leaves the eye through the "conventional
      outflow pathway", consisting of the trabecular meshwork, Schlemm's canal,
      collector channels, an intrasceral plexus and the episcleral veins. While the
      trabecular meshwork is well characterized, little is known about anatomical and
      functional features of the peripheral outflow tract beyond Schlemm's canal. The
      emergence of minimally-invasive glaucoma surgery directly targeting the outflow
      resistance in the trabecular meshwork has elicited growing interest in these
      structures. We used time-of-flight magnetic resonance imaging in ex vivo bovine
      eyes to map fluid flow under physiological conditions. We were able to identify
      the peripheral outflow vessels solely by the signal detected from the fluid flow
      inside their lumina. A question of clinical relevance is, whether localized
      opening of the trabecular meshwork leads to only localized or to a 360 degrees 
      increase in intrascleral flow. To address this, a goniotomy ab interno was
      performed in 3 eyes and the flow signal intensity was quantified sectorially. A
      significant increase in fluid flow was observed in the sector distal to the
      goniotomy (p = 0.0005) but not in the other sectors (p = 0.1). As a proof of
      concept we demonstrated that TOF-MRI based detection of flow in the peripheral
      aqueous outflow tract is feasible. The functional link observed between
      trabecular meshwork sectors and their distal outflow tract sectors may be
      relevant for minimally-invasive glaucoma surgery in humans.

PMID- 29074389
TI  - Different effects of silica added internal or external on in vitro dissolution of
      indomethacin hot-melt extrudates.
AB  - The purpose of this work was to investigate the effect on the dissolution
      behavior when silica was added in different ways. The solid dispersion was
      prepared by hot-melt extrusion (HME) using indomethacin (IND) as a model drug and
      Kollidon VA64 as a carrier. In order to change the dissolution behavior, the
      silica was added during or after the HME respectively, to obtain the
      corresponding silica internal-added solid dispersion (InSD) and silica external
      added solid dispersion (ExSD). According to the results, the internal-added
      silicon dioxide could reduce the dissolution rate from 66.91%/h to 24.12%/h and
      the water infiltration rate from 0.37mm/h to 0.16mm/h in the phosphate buffer
      solution (PBS) of pH 6.8, so the formulation of InSD had a significant sustained
      release effect. But the infiltration rate of the ExSD was increased to 13.22mm/h
      when silica was added external, and the density of VA64 in the powder was
      decreased from 541.87mg/cm3 to 141.87mg/cm3, leading to a weak resistance to the
      external force, and the powder was easy to be dispersed after wetted by water so
      that the formulation of ExSD had a relatively higher dissolution rate. This
      phenomenon was more visible when the phosphate buffer solution was changed to pH
      5.6 in which the API was more difficult to be dissolved. Accordingly, different
      addition ways of aerosil would change release behavior of the HME preparation.

PMID- 29074390
TI  - Understanding die fill variation during mini-tablet production.
AB  - Reproducibility of die fill during tablet production is critical to ensure
      consistent tablet drug content and mechanical attributes. In the production of
      mini-tablets, tablets smaller than 6mm, achievement of uniform die fill is much
      more challenging. Powder flow is often associated with die fill accuracy but this
      relationship has not been well characterised especially for mini-tablets. In this
      study, flow properties of different types of granules were characterised. Mini
      tablets of 1.8 and 3mm diameters were prepared from the granules using a rotary
      press with multiple-tip compression tooling. A methodology was established to
      evaluate mini-tablet die fill variation within and across compaction cycles using
      data from compression roller displacement and mini-tablet weight. Both sizes of
      mini-tablets showed similar extents of inter-cycle weight variation that could be
      associated with granules' inter-particulate friction. However, smaller mini
      tablets had higher intra-cycle weight variation due to their narrower die
      orifices. Multivariate and univariate analyses suggested that gravity fill
      influenced intra-cycle weight variation of 3mm mini-tablets while suction fill
      was associated with that of 1.8mm mini-tablets. Possible differences in die fill
      mechanisms between the mini-tablet sizes were identified and this provided a
      better insight into die fill variations during the production of mini-tablets.

PMID- 29074391
TI  - Chitosan based Pickering emulsion as a promising approach for topical application
      of rutin in a solubilized form intended for wound healing: In vitro and in vivo
      study.
AB  - The aim of the present study is to formulate the hydrophobic drug rutin in a
      solubilized form, intended for wound healing, via its loading into a novel
      Pickering emulsion stabilized by self aggregated chitosan particles (SACP). Rutin
      loaded Pickering emulsion formulae were prepared using a high speed homogenizer.
      They were characterized by drop test, optical microscopy, droplet size and zeta
      potential determination. The results revealed that SACP have a nano size and a
      contact angle of 42.47+/-1.19 degrees  that tend to stabilize O/W emulsion. The
      droplet size of all investigated formulations ranged between 5.8+/-1.1 and 18.7+/
      3.4MUm. The long term stability study revealed that formulae containing 20% and
      30% oily phase were stable against coalescence, the droplet size was slightly
      increased with zeta potential ranged from -48.1+/-4.7 to -78.4+/-4.1mV, during
      the storage period up to 5 months, indicating good stability. The release of
      rutin was almost 100% within 24h. Treatment of the wounded skin tissue of the
      Albino rats with the selected formula, for ten days, revealed almost complete
      healing. Biochemical analysis for oxidative stress markers, hyaluronic acid and
      collagen type I in addition to histopathological study were performed. The
      results suggested that the sustained release of rutin in a solubilized form as
      well as the synergistic effect of other components of the prepared Pickering
      emulsion could have a potential wound healing effect.

PMID- 29074392
TI  - Effects of minocycline and doxycycline against terbutaline induced early
      postnatal autistic changes in albino rats.
AB  - The current study was initiated to explicate the shielding response of
      minocycline and doxycycline against early postnatal neurological damage and
      behavioral alteration convinced by terbutaline. Toxicity was induced by
      terbutaline at three successive days in the pups. The pups were scrutinized for
      behavioral, biochemical and inflammatory markers. Subsequent treatment with test
      drugs commenced a favorable effect on the autistic symptoms with more safeguard
      by doxycycline. The study also recognized peripheral inflammatory reactions and
      increased nitric oxide (NO) through terbutaline which was curtailed down by test
      drugs, with the much more noticeable effect of doxycycline. The GC-FID analysis
      and histopathological evaluation of the brain tissue elicited more pronounced
      protection by doxycycline. Doxycycline was also evident with remarkable down
      regulation Pgp 9.5 [Ubiquitin carboxy-terminal hydrolase L1 (UCHL-1)] expression
      in the brain tissue in comparison to minocycline.

PMID- 29074393
TI  - DCF1 subcellular localization and its function in mitochondria.
AB  - Dendritic cell factor 1 (DCF1) is a transmembrane protein that plays important
      roles in regulating neural stem cell differentiation and dendritic spine
      formation. Apart from its cytoplasmic functions, DCF1 plays a role in autophagy
      during the regulation of amyloid precursor proteins. However, the subcellular
      localization of DCF1 remains unknown. Therefore, in this study, DCF1 tagged with
      green fluorescent protein was transiently expression in HelaS3 and HEK293T cells.
      The results showed that DCF1 was widely expressed in different organelles,
      including the mitochondria, Golgi apparatus, endoplasmic reticulum, endosomes and
      lysosomes. An iodixanol step gradient further confirmed that DCF1 is localized to
      the mitochondria, endosomes, lysosomes, endoplasmic reticulum, and proteasome.
      Finally, functional analysis of the mitochondria revealed that DCF1 affected the
      expression and localization of MGST1. This study presents a comprehensive
      evaluation of the subcellular localization of DCF1, which provides important
      information on complex functions mediated by DCF1.

PMID- 29074394
TI  - N6-adenine DNA methylation demystified in eukaryotic genome: From biology to
      pathology.
AB  - N6-methyl-2'-deoxyadenosine (m6dA) is a well characterized DNA modification in
      prokaryotes. Its existence in eukaryotic DNA remained doubtful until recently.
      Evidence suggests that the m6dA levels decrease with the increasing complexity of
      eukaryotic genomes. Analysis of m6dA levels in genome of lower eukaryotes reveals
      its role in gene regulation, nucleosome positioning and early development. In
      higher eukaryotes m6dA is enriched in nongenic region compared to genic region,
      preferentially in chromosome X and 13 suggesting a chromosome bias. High levels
      of m6dA during embryogenesis as compared to adult tissues are indicative of its
      importance during development and possible association with regeneration
      capabilities. Further, decreased levels of m6dA in diabetic patients has been
      correlated with expression of Fat mass and obesity-associated (FTO) which acts as
      m6A demethylase. m6dA levels have also been reported to be decreased in different
      types of cancers. The present review highlights the role of m6dA modification in
      eukaryotic genomes and its functional importance in regulation of physiological
      and pathological processes.

PMID- 29074395
TI  - Epigenetics of malignant melanoma.
AB  - Patients with malignant melanoma generally have a good prognosis if the disease
      presents prior to metastasis. Due to progress with targeted and immunotherapies,
      the median survival of metastatic melanoma patients is now over 2 years. The
      disease is characterised by one of the highest somatic mutation rates observed
      amongst cancer types, with a specific mutational signature based on UV radiation
      damage evident. Highly prevalent mutations, such as the BRAFV600E, in the MAPK
      cascade indicate truncal involvement of this pathway in the earliest stage of
      melanoma. The molecular sub-classification of melanoma based on genetic
      alterations is now well established. This has paved the way for researchers in
      epigenetics to investigate specific pathways of known importance, and the
      involvement of the diverse range of epigenetic mechanisms. Herein, we review the
      literature to highlight that epigenetic alterations are integrally involved in
      this malignancy. We focus on the most current evidence around the epigenetic
      mechanisms: DNA methylation and demethylation including 5-hydroxy-methylcytosine;
      histone post-translational modifications including variant histones; chromatin
      remodelling complexes and in particular the polycomb-repressive complex PRC2 and
      its histone methyltransferase subunit EZH2; and non-coding RNAs. Each mechanism
      is described generally, studies involving melanoma are assessed and clinical
      relevance is highlighted where possible.

PMID- 29074396
TI  - Translocation and dissemination of botulinum neurotoxin from the intestinal
      tract.
AB  - Botulinum neurotoxins (BoNTs) are potent toxins which induce flaccid paralysis by
      inhibiting the release of acetylcholine at the neuromuscular junctions. They
      associate with non-toxic proteins (ANTPs or NAPs) to form complexes of various
      sizes which are resistant to acidic pH and protease degradation. BoNT trafficking
      from the digestive tract to the target neurons is still a matter of debate. BoNTs
      use different strategies to pass through the intestinal barrier including passage
      of BoNT complexes containing hemagglutinins (HAs) via M cells, HA-dependent
      perturbation of E-cadherin intercellular junctions between enterocytes and
      paracellular passage of BoNT complexes, and transcytosis of BoNT free of NAPs
      through certain intestinal epithelial cells. Then, BoNTs target neuronal cells,
      preferentially cholinergic neurons, in the intestinal mucosa and submucosa. The
      precise mode of BoNT dissemination until the final target neuro-muscular
      junctions is still elusive.

PMID- 29074397
TI  - Helix structure of the double-stranded DNA for aptameric biosensing and imaging
      of cytochrome c.
AB  - Here, a method is introduced for construction the aptameric biosensor for
      biosensing detection of cytochrome C (CYC) based on chain-shape structure of
      aptasensor by using highly dispersed silver nanoparticles (AgNPs) on acid
      oxidized carbon nanotube (CNTs) substrate. The animated capture probe (ssDNA1)
      and CYC-aptamer (ssDNA2) was immobilized on AgNPs/CNTs surface by covalent amide
      bonds formed by the carboxyl groups on the nanotubes and the amino groups on the
      oligonucleotides and hybridization, respectively. In this protocol, the nucleic
      acids at both ends of the ssDNA1 were sequenced to be complementary (tailor-made
      ssDNA1). The helix structure of the double-stranded DNA was fabricated by
      hybridizing ssDNA2 with its complementary sequence (ssDNA1). CYC-aptamer could be
      forced to dissociate from the sensing interface after CYC triggered structure
      switching of the aptamer and ssDNA1 thus tend to form a chain-shape structure
      through the hybridization of the complementary sequences at both its ends. The
      proposed assay permitted to detect CYC in the linear range of 0.01-750 nM with a
      very low limit of detection (LOD) (1.66 pM). In addition, the specificity of this
      sensing system for the detection of CYC was also demonstrated by using albumin,
      fructose, myoglobin, and hemoglobin.

PMID- 29074399
TI  - Reply to: "Cerebral resuscitation: Shifting away from the basics" (Letter to
      editor on post-resuscitation arterial oxygen and carbon dioxide and outcomes
      after out-of-hospital cardiac arrest).

PMID- 29074400
TI  - Paternal use of thiopurines and methotrexate: Are we reassured enough?

PMID- 29074398
TI  - Design of titanium nitride- and wolfram carbide-doped RGO/GC electrodes for
      determination of gallic acid.
AB  - In the present paper, the electrochemical behavior and the properties of two
      modified glassy carbon (GC) electrodes used for quantification of gallic acid in
      sweet wines were compared. A comparative study was conducted between titanium
      nitride- or wolfram carbide-doped reduced graphene oxide, labeled as TNrGO and
      WCrGO, respectively, modified GC electrodes, which are promising composite
      nanomaterials for electroanalytical applications. For the first time, WCrGO was
      synthesized and its electroanalytical properties compared with those of TNrGO.
      Results showed that the proposed materials exhibited enhanced characteristics,
      e.g., low limits of detection (1.1 MUM and 3.1 MUM for TNrGO and WCrGO,
      respectively), wide linear ranges (for TNrGO 4.5-76 MUM and for WCrGO 10-100
      MUM), low adsorption, and low background current, which make them promising
      candidates for electrochemical sensing applications.

PMID- 29074401
TI  - [Implementing vaccination recommendations in discharge letters].
AB  - OBJECTIVES: There is still a lack of attention paid to the subject of
      vaccinations indicated for people with chronic disease, so the vaccination rates
      in this field are low or hardly known. Hospitals only play a minor part in the
      vaccination subject, although they play a big part in the treatment of
      chronically ill patients. METHODS: In this study we wanted to test the
      practicability of the implementation of vaccination recommendations in discharge
      letters as a chance to give the subject more attention and involve hospital
      doctors in the vaccination process. In addition, we analyzed clinical und primary
      care physicians' attitudes towards these recommendations and vaccination in
      general. RESULTS: 88.5% of the general practitioners and 81.3% of the hospital
      doctors consider vaccination recommendations in discharge letters reasonable.
      86.3% of the general practitioners said they were willing to perform the
      recommended vaccinations. The main responsibility in the vaccination process is
      clearly allocated to general practitioners, but many hospital doctors want to
      raise the level of attention given to the vaccination subject in their
      departments. CONCLUSION: Standardized implementation of vaccination
      recommendations in discharge letters is a reasonable way to involve hospital
      doctors in the vaccination process as part of the preventive care services for
      chronically ill patients. At the same time, general practitioners will be
      regularly informed about indicated vaccinations for the individual patient.

PMID- 29074402
TI  - Ergothioneine stands out from hercynine in the reaction with singlet oxygen:
      Resistance to glutathione and TRIS in the generation of specific products
      indicates high reactivity.
AB  - The candidate vitamin ergothioneine (ET), an imidazole-2-thione derivative of
      histidine betaine, is generally considered an antioxidant. However, the precise
      physiological role of ET is still unresolved. Here, we investigated in vitro the
      hypothesis that ET serves specifically to eradicate noxious singlet oxygen (1O2).
      Pure 1O2 was generated by thermolysis at 37 degrees C of N,N'-di(2,3
      dihydroxypropyl)-1,4-naphthalenedipropanamide 1,4-endoperoxide (DHPNO2). Assays
      of DHPNO2 with ET or hercynine (= ET minus sulfur) at pH 7.4 were analyzed by LC
      MS in full scan mode to detect products. Based on accurate mass and product ion
      scan data, several products were identified and then quantitated as a function of
      time by selected reaction monitoring. All products of hercynine contained, after
      a [4+2] cycloaddition of 1O2, a carbonyl at position 2 of the imidazole ring. By
      contrast, because of the doubly bonded sulfur, we infer from the products of ET
      as the initial intermediates a 4,5-dioxetane (after [2+2] cycloaddition) and
      hydroperoxides at position 4 and 5 (after Schenck ene reactions). The generation
      of single products from ET, but not from hercynine, was fully resistant to a
      large excess of tris(hydroxymethyl)aminomethane (TRIS) or glutathione (GSH). This
      suggests that 1O2 markedly favors ET over GSH (at least 50-fold) and TRIS (at
      least 250-fold) for the initial reaction. Loss of ET was almost abolished in 5mM
      GSH, but not in 25mM TRIS. Regeneration of ET seems feasible, since some ET
      products - by contrast to hercynine products - decomposed easily in the MS
      collision cell to become aromatic again.

PMID- 29074403
TI  - Speech perception in autism spectrum disorder: An activation likelihood
      estimation meta-analysis.
AB  - Autism spectrum disorder (ASD) is often characterized by atypical language
      profiles and auditory and speech processing. These can contribute to aberrant
      language and social communication skills in ASD. The study of the neural basis of
      speech perception in ASD can serve as a potential neurobiological marker of ASD
      early on, but mixed results across studies renders it difficult to find a
      reliable neural characterization of speech processing in ASD. To this aim, the
      present study examined the functional neural basis of speech perception in ASD
      versus typical development (TD) using an activation likelihood estimation (ALE)
      meta-analysis of 18 qualifying studies. The present study included separate
      analyses for TD and ASD, which allowed us to examine patterns of within-group
      brain activation as well as both common and distinct patterns of brain activation
      across the ASD and TD groups. Overall, ASD and TD showed mostly common brain
      activation of speech processing in bilateral superior temporal gyrus (STG) and
      left inferior frontal gyrus (IFG). However, the results revealed trends for some
      distinct activation in the TD group showing additional activation in higher-order
      brain areas including left superior frontal gyrus (SFG), left medial frontal
      gyrus (MFG), and right IFG. These results provide a more reliable neural
      characterization of speech processing in ASD relative to previous single
      neuroimaging studies and motivate future work to investigate how these brain
      signatures relate to behavioral measures of speech processing in ASD.

PMID- 29074404
TI  - Are rodent models of Parkinson's disease behaving as they should?
AB  - In recent years our understanding of Parkinson's disease has expanded both in
      terms of pathological hallmarks as well as relevant genetic influences. In
      parallel with the aetiological discoveries a multitude of PD animal models have
      been established. The vast majority of these are rodent models based on
      environmental, genetic and mechanistic insight. A major challenge in many of
      these models is their ability to only recapitulate some of the complex disease
      features seen in humans. Although symptom alleviation and clinical signs are of
      utmost importance in therapeutic research many of these models lack comprehensive
      behavioural testing. While non-motor symptoms become increasingly important as
      early diagnostic markers in PD, they are poorly characterized in rodents. In this
      review we look at well-established and more recent animal models of PD in terms
      of behavioural characterization and discuss how they can best contribute to
      progression in Parkinson's research.

PMID- 29074405
TI  - The Hajj and Umrah: Health protection matters.

PMID- 29074406
TI  - The CDC Yellow Book app 2018.

PMID- 29074407
TI  - Adaptation of vectors and drug-inducible systems for controlled expression of
      transgenes in the tumor microenvironment.
AB  - Biological therapies based on recombinant proteins such as antibodies or
      cytokines are continuously improving the repertoire of treatments against cancer.
      However, safety and efficacy of this approach is often limited by inappropriate
      biodistribution and pharmacokinetics of the proteins when they are administered
      systemically. Local administration of gene therapy vectors encoding these
      proteins would be a feasible alternative if they could mediate long-term and
      controlled expression of the transgene after a single intratumoral
      administration. We describe a new vector platform specially designed for this
      purpose. Different combinations of transactivators and promoters were evaluated
      to obtain a fully humanized inducible system responsive to the well-characterized
      drug mifepristone. The optimal transactivator conformation was based on DNA
      binding domains from the chimeric protein ZFHD1 fused to the progesterone
      receptor ligand binding domain and the NFkb p65 activation domain. The expression
      of this hybrid transactivator under the control of the elongation factor 1alpha
      (EF1alpha) or the chimeric CAG promoters ensured functionality of the system in a
      variety of cancer types. Expression cassettes with luciferase as a reporter gene
      were incorporated into High-Capacity adenoviral vectors (HC-Ad) for in vivo
      evaluation. Systemic administration of the vectors into C57BL/6 mice revealed
      that the vector based on the EF1alpha promoter (HCA-EF-ZP) allows tight control
      of transgene expression and remains stable for at least two months, whereas the
      CAG promoter suffers a progressive inactivation. Using an orthotopic pancreatic
      cancer model in syngeneic C57BL/6 mice we show that the local administration of
      HCA-EF-ZP achieves better tumor/liver ratio of luciferase production than the
      intravenous route. However, regional spread of the vector led to substantial
      transgene expression in peritoneal organs. We reduced this leakage through
      genetic modification of the vector capsid to display RGD and poly-lysine motifs
      in the fiber knob. Safety and antitumor effect of this gene therapy platform was
      demonstrated using interleukin-12 as a therapeutic gene. In conclusion, we have
      developed a new tool that allows local, sustained and controlled production of
      therapeutic proteins in tumors.

PMID- 29074408
TI  - Using siRNA-based spherical nucleic acid nanoparticle conjugates for gene
      regulation in psoriasis.
AB  - Psoriasis is a T-cell-mediated skin disease with autoimmune nature that is
      generally not observed in animals, this lack of a relevant experimental animal
      model of psoriasis has hindered the investigation of pathogenesis of disease.
      Application and systemic delivery of small interfering RNAs offer many effective
      therapeutic advantages for gene regulation in the skin. In this study, we present
      an IMQ animal model of psoriasis and designed a safe fusion peptide carrier,
      spherical nucleic acid gold nanoparticles conjugate, to improve penetration of
      the siRNA into the cells and skin and their targeting ability to gene regulation.
      We evaluated the model of psoriasis and EGFR siRNA treatment (as spherical
      nucleic acid nanoparticles), phenotypically (signs of erythema, scaling,
      inflammation and thickening), microscopic evaluation of cell proliferation and
      immunohistochemically evaluation of CD3, CD4, and CD8 markers. Also, we monitored
      suppression of EGF&EGFR genes after treatment of A431 cells by SNA-NCs. The
      expression of genes was validated by qRT-PCR in human skin cells. The results
      showed that the SNA-NCs were stable and non-toxic. In vitro experiments indicated
      that EGF&EGFR siRNAs conjugated with spherical nucleic acid gold nanoparticles
      can significantly reduce gene expression in cells. In vivo experiments showed
      that the topical application of siRNAs delivered by SNA-NCs through the skin can
      significantly inhibit the proliferation of cells. Microscopic evaluation of mice
      back skin and immunohistochemistry process approved Inhibitory effect of SNA-NCs
      siRNA in the mouse model of psoriasis. Since the proliferation of T cells was
      crucial for the development of a psoriatic phenotype. These results demonstrate
      that topical application of SNA-NCs siRNA may improve psoriatic-like skin lesions
      by suppressing gene expression and functional activity of T cell production.

PMID- 29074409
TI  - Global prevalence of injecting drug use and sociodemographic characteristics and
      prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage
      systematic review.
AB  - BACKGROUND: Sharing of equipment used for injecting drug use (IDU) is a
      substantial cause of disease burden and a contributor to blood-borne virus
      transmission. We did a global multistage systematic review to identify the
      prevalence of IDU among people aged 15-64 years; sociodemographic characteristics
      of and risk factors for people who inject drugs (PWID); and the prevalence of
      HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. METHODS:
      Consistent with the GATHER and PRISMA guidelines and without language
      restrictions, we systematically searched peer-reviewed databases (MEDLINE,
      Embase, and PsycINFO; articles published since 2008, latest searches in June,
      2017), searched the grey literature (websites and databases, searches between
      April and August, 2016), and disseminated data requests to international experts
      and agencies (requests sent in October, 2016). We searched for data on IDU
      prevalence, characteristics of PWID, including gender, age, and sociodemographic
      and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID.
      Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among
      PWID were selected and, where multiple estimates were available, pooled for each
      country via random effects meta-analysis. So too were eligible data on percentage
      of PWID who were female; younger than 25 years; recently homeless; ever arrested;
      ever incarcerated; who had recently engaged in sex work, sexual risk, or
      injecting risk; and whose main drugs injected were opioids or stimulants. We
      generated regional and global estimates in line with previous global reviews.
      FINDINGS: We reviewed 55 671 papers and reports, and extracted data from 1147
      eligible records. Evidence of IDU was recorded in 179 of 206 countries or
      territories, which cover 99% of the population aged 15-64 years, an increase of
      31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a
      review in 2008. IDU prevalence estimates were identified in 83 countries. We
      estimate that there are 15.6 million (95% uncertainty interval [UI] 10.2-23.7
      million) PWID aged 15-64 years globally, with 3.2 million (1.6-5.1 million) women
      and 12.5 million (7.5-18.4 million) men. Gender composition varied by location:
      women were estimated to comprise 30.0% (95% UI 28.5-31.5) of PWID in North
      America and 33.4% (31.0-35.6) in Australasia, compared with 3.1% (2.1-4.1) in
      south Asia. Globally, we estimate that 17.8% (10.8-24.8) of PWID are living with
      HIV, 52.3% (42.4-62.1) are HCV-antibody positive, and 9.0% (5.1-13.2) are HBV
      surface antigen positive; there is substantial geographic variation in these
      levels. Globally, we estimate 82.9% (76.6-88.9) of PWID mainly inject opioids and
      33.0% (24.3-42.0) mainly inject stimulants. We estimate that 27.9% (20.9-36.8) of
      PWID globally are younger than 25 years, 21.7% (15.8-27.9) had recently (within
      the past year) experienced homelessness or unstable housing, and 57.9% (50.5
      65.2) had a history of incarceration. INTERPRETATION: We identified evidence of
      IDU in more countries than in 2008, with the new countries largely consisting of
      low-income and middle-income countries in Africa. Across all countries, a
      substantial number of PWID are living with HIV and HCV and are exposed to
      multiple adverse risk environments that increase health harms. FUNDING:
      Australian National Drug and Alcohol Research Centre, Australian National Health
      and Medical Research Council, Open Society Foundation, World Health Organization,
      the Global Fund, and UNAIDS.

PMID- 29074411
TI  - A protective role of Galphaq-RGS2 loop activator on streptozotocin induced
      diabetic complications in rats: An independent on elevated serum glucose level
      modulation.
AB  - An overactivation of Galphaq dependent signaling pathway is crucial for
      development of metabolic and vascular abnormalities in diabetes. Therefore, our
      objective was to study effects of Galphaq-RGS2 loop activator (1-(5-chloro-2
      hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one) on STZ
      induced diabetic complications in rats. Animals were divided into four groups;
      normal rats, diabetic rats (Streptozotocin, STZ, 60mg/kg, i.p.), Galphaq-RGS2
      loop activator (1mg/kg/d, i.p., 15 d, at 6 wk after citrate buffer or STZ
      administration, respectively) treated normal rats and diabetic rats. At the end
      of 8 wk, the metabolic parameters, hemodynamic parameters, in-vivo vascular
      reactivity and aortic anti-oxidant status were evaluated. A treatment of Galphaq
      RGS2 loop activator significantly decreased serum cholesterol (P < 0.001),
      triglyceride (P < 0.01), systolic/diastolic/mean arterial blood pressure (P <
      0.001), lactate dehydrogenase (P < 0.001), cardiac selective creatinine kinase (P
      < 0.001), urea (P < 0.05), creatinine (P < 0.001), aortic superoxide dismutase (P
      < 0.05) and catalase(P < 0.05) in diabetic rats whereas increased basal (P <
      0.05) and stimulated (acetylcholine (P < 0.01) and nitroglycerine (P < 0.05))
      serum nitric oxide level without affecting elevated serum glucose level. The
      nitroglycerin stimulated NO production was significantly (P < 0.01) increased by
      Galphaq-RGS2 loop activator administration in normal rats, too. Collectively,
      Galphaq-RGS2 loop activator protects rats against streptozotocin induce
      hemodynamic and metabolic modulation without affecting elevated serum glucose
      level.

PMID- 29074412
TI  - Molecular mechanism of doxorubicin-induced cardiomyopathy - An update.
AB  - Doxorubicin is utilized for anti-neoplastic treatment for several decades. The
      utility of this drug is limited due to its side effects. Generally, doxorubicin
      toxicity is originated from the myocardium and then other organs are also ruined.
      The mechanism of doxorubicin is intercalated with the DNA and inhibits
      topoisomerase 2. There are various signalling mechanisms involved in doxorubicin
      cardiotoxicity. First and foremost, the doxorubicin-induced cardiotoxicity is due
      to oxidative stress. Cardiac mitochondrial damage is supposed after few hours
      following the revelation of doxorubicin. This has led important new uses for the
      mechanism of doxorubicin-induced cardiotoxicity and novel avenues of
      investigation to determine better pharmacotherapies and interventions for the
      impediment of cardiotoxicity. The idea of this review is to bring up to date the
      recent findings of the mechanism of doxorubicin cardiomyopathies such as calcium
      dysregulation, endoplasmic reticulum stress, impairment of progenitor cells,
      activation of immune, ubiquitous system and some other parameters.

PMID- 29074410
TI  - Global, regional, and country-level coverage of interventions to prevent and
      manage HIV and hepatitis C among people who inject drugs: a systematic review.
AB  - BACKGROUND: People who inject drugs (PWID) are a key population affected by the
      global HIV and hepatitis C virus (HCV) epidemics. HIV and HCV prevention
      interventions for PWID include needle and syringe programmes (NSP), opioid
      substitution therapy (OST), HIV counselling and testing, HIV antiretroviral
      therapy (ART), and condom distribution programmes. We aimed to produce country
      level, regional, and global estimates of coverage of NSP, OST, HIV testing, ART,
      and condom programmes for PWID. METHODS: We completed searches of peer-reviewed
      (MEDLINE, Embase, and PsycINFO), internet, and grey literature databases, and
      disseminated data requests via social media and targeted emails to international
      experts. Programme and survey data on each of the named interventions were
      collected. Programme data were used to derive country-level estimates of the
      coverage of interventions in accordance with indicators defined by WHO, UNAIDS,
      and the UN Office on Drugs and Crime. Regional and global estimates of NSP, OST,
      and HIV testing coverage were also calculated. The protocol was registered on
      PROSPERO, number CRD42017056558. FINDINGS: In 2017, of 179 countries with
      evidence of injecting drug use, some level of NSP services were available in 93
      countries, and there were 86 countries with evidence of OST implementation. Data
      to estimate NSP coverage were available for 57 countries, and for 60 countries to
      estimate OST coverage. Coverage varied widely between countries, but was most
      often low according to WHO indicators (<100 needle-syringes distributed per PWID
      per year; <20 OST recipients per PWID per year). Data on HIV testing were sparser
      than for NSP and OST, and very few data were available to estimate ART access
      among PWID living with HIV. Globally, we estimate that there are 33 (uncertainty
      interval [UI] 21-50) needle-syringes distributed via NSP per PWID annually, and
      16 (10-24) OST recipients per 100 PWID. Less than 1% of PWID live in countries
      with high coverage of both NSP and OST (>200 needle-syringes distributed per PWID
      and >40 OST recipients per 100 PWID). INTERPRETATION: Coverage of HIV and HCV
      prevention interventions for PWID remains poor and is likely to be insufficient
      to effectively prevent HIV and HCV transmission. Scaling up of interventions for
      PWID remains a crucial priority for halting the HIV and HCV epidemics. FUNDING:
      Open Society Foundations, The Global Fund, WHO, UNAIDS, United Nations Office on
      Drugs and Crime, Australian National Drug and Alcohol Research Centre, University
      of New South Wales Sydney.

PMID- 29074413
TI  - Galantamine attenuates N,N-dimethyl hydrazine induced neoplastic colon damage by
      inhibiting acetylcholinesterase and bimodal regulation of nicotinic cholinergic
      neurotransmission.
AB  - The present study reveals the effect of galantamine (GAL) against 1, 2
      dimethylhydrazine (DMH) induced colon cancer. Wistar albino rats were arbitrarily
      divided into four groups (n = 8). Group 1 served as normal control (normal
      saline, 3ml/kg/day, p.o.); group 2, 3 and 4 received DMH (20mg/kg/week, s.c.),
      for 6 weeks; groups 3 and 4 also received GAL (2 and 4mg/kg/day, p.o) for 6
      weeks. DMH treated rats showed decreased heart rate variability (HRV) factors,
      increased incidence of aberrant crypt foci (ACF), increased thiobarbituric acid
      reactive substances (TBARs) along with the decrease in the enzymatic activity of
      superoxide dismutase (SOD) and catalase. Increased levels of inflammatory marker
      cyclooxygenase (COX) and lipoxygenase (LOX) was also evident in DMH treated
      animals. The colonic surface architecture was studied using scanning electron
      microscopy revealed aberrant crypts(X500) and neoplastic nodules (X2000). GAL
      treatment helped to minimize the ACF count, restored oxidative stress and
      inflammatory markers favorably. To further validate our results, our study was
      directed to define the effect of GAL on acetylcholine neurotransmission using a
      simple model organism, Caenorhabditis elegans (C. elegans). Increased synaptic
      cholinergic transmission by GAL (32uM) was evident in the worms when studied
      through aldicarb assay. However, GAL (32uM) treatment negatively modulated alpha7
      nicotinic acetylcholine receptor (alpha7nAch receptor), when evaluated using the
      levamisole assay. GAL (32uM) treatment down regulated the genomic expression of
      ace-1, ace-2 along with unc-29, unc-38, and unc-50 (essential components of
      alpha7 nAch receptor). GAL by inhibiting AchE and regulating Alpha7nACh activity
      can improve cholinergic neurotransmission.

PMID- 29074414
TI  - Non-adrenergic vasoconstriction and vasodilatation of guinea-pig aorta by beta
      phenylethylamine and amphetamine - Role of nitric oxide determined with L-NAME
      and NO scavengers.
AB  - Sympathomimetic and trace amines, including beta-phenylethylamine (PEA) and
      amphetamine, increase blood pressure and constrict isolated blood vessels. By
      convention this is regarded as a sympathomimetic response, however, recent
      studies suggest trace amine-associated receptor (TAAR) involvement. There is also
      uncertainty whether these amines also release nitric oxide (NO) causing opposing
      vasodilatation. These questions were addressed in guinea-pig isolated aorta, a
      species not previously examined. Guinea-pig aortic rings were set up to measure
      contractile tension. Cumulative concentration-response curves were constructed
      for the reference alpha-adrenoceptor agonist, phenylephrine, PEA or d-amphetamine
      before and in the presence of vehicles, the alpha1-adrenoceptor antagonist,
      prazosin (1uM), the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine (L
      NAME), or NO scavengers, curcumin and astaxanthin. Prazosin inhibited
      phenylephrine contractions with low affinity consistent with alpha1L
      adrenoceptors. However, PEA and amphetamine were not antagonised, indicating non
      adrenergic responses probably via TAARs. L-NAME potentiated contractions to PEA
      both in the absence and presence of prazosin, indicating that PEA releases NO to
      cause underlying opposing vasodilatation, independent of alpha1-adrenoceptors. L
      NAME also potentiated amphetamine and phenylephrine. PEA was potentiated by the
      NO scavenger astaxanthin but less effectively. Curcumin, an active component of
      turmeric, however, inhibited PEA. Trace amines therefore constrict blood vessels
      non-adrenergically with an underlying NO-mediated non-adrenergic vasodilatation.
      This has implications in the pressor actions of these amines when NO is
      compromised.

PMID- 29074415
TI  - Non-steroidal anti-inflammatory drugs are safe with respect to the transcriptome
      of human dermal fibroblasts.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) provide important benefits to
      millions of patients, but are associated with a number of serious adverse events.
      These adverse drug reactions are an important clinical issue and a serious public
      health risk. While most unfortunate responses in human to NSAIDs are mild and may
      disappear after decreasing the dose or withdrawal of the drug, some of them can
      produce serious outcomes. Currently, little is known regarding the effects of
      NSAIDs on global RNA expression in normal, non-transformed cells. Therefore, in
      this report, the effect of NSAIDs, COX-nonspecific and COX-2-specific inhibitors,
      indomethacin and nimesulide respectively, commonly used medications worldwide for
      the reduction of pain, fever, inflammation and stiffness, on transcriptomic
      signature of human dermal fibroblasts was investigated. A total of 3803
      differentially expressed genes with a fold change greater than or equal to 1.3
      and below than or equal to 0.7 for whole genome transcripts, with a P value of <
      0.05 were identified in response to all applied conditions. We found that
      although the total number of deregulated genes was relatively high at such
      criteria, changes in fibroblast transcriptome profile after treatment at selected
      experimental conditions were however smallish, as the selected drugs slightly
      modulate transcriptome with only a few genes with expression altered a bit more
      than twice. Nevertheless, transcriptomic data has its own limitations and it
      cannot reflect all post-transcriptional changes, which in turn may cause same
      risks, especially for a long time of medication.

PMID- 29074416
TI  - Clonidine preconditioning improved cerebral ischemia-induced learning and memory
      deficits in rats via ERK1/2-CREB/ NF-kappaB-NR2B pathway.
AB  - Clonidine, a classical alpha-2 adrenergic agonists, has been shown to antagonize
      brain damage caused by hypoxia, cerebral ischemia and excitotoxicity and reduce
      cerebral infarction volume in recent studies. We herein investigate the
      regulatory effect and possible underlying mechanism of clonidine on learning and
      memory in rats with cerebral ischemia. The cerebral ischemia rat model was
      established by right middle cerebral artery occlusion for 2h and reperfusion for
      28 days. Drugs were administrated to the rats for consecutive 7 days
      intraperitoneally and once again on the day of surgery. The learning and memory
      in rats was assayed by Morris water maze. Moreover, protein expression levels of
      NMDAR2B (NR2B)/ phosphor - NR2B, ERK1/2/phosphor- ERK1/2, CREB/phosphor-CREB and
      NF-kappaB/phosphor-NF-kappaB in the cortex and hippocampus of the rats were
      assayed by western blotting. Our results demonstrated that clonidine treatment
      significantly abrogated the negative effect induced by cerebral ischemia on the
      learning and memory in the rats. In the Western blotting assay, clonidine
      treatment led to significant up-regulation of the expression level of NR2B and
      Phospho-NR2B in the hippocampus of the rats when compared with the cerebral
      ischemia group. Furthermore, clonidine also significantly decreased the protein
      expression levels of ERK1/2, Phospho-ERK1/2, CREB, Phospho-CREB and Phospho-NF
      kappaB in the hippocampus of the rats when compared with the cerebral ischemia
      group. In conclusion, clonidine could improve the learning and memory ability of
      rats with cerebral ischemia, and NR2B, ERK1/2, CREB, NF-kappaB were involved in
      this effect.

PMID- 29074418
TI  - APROBA-Plus: A probabilistic tool to evaluate and express uncertainty in hazard
      characterization and exposure assessment of substances.
AB  - To facilitate the application of probabilistic risk assessment, the WHO released
      the APROBA tool. This tool applies lognormal uncertainty distributions to the
      different aspects of the hazard characterization, resulting in a probabilistic
      health-based guidance value. The current paper describes an extension, APROBA
      Plus, which combines the output from the probabilistic hazard characterization
      with the probabilistic exposure to rapidly characterize risk and its uncertainty.
      The uncertainty in exposure is graphically compared with the uncertainty in the
      target human dose, i.e. the dose that complies with the specified protection
      goals. APROBA-Plus is applied to several case studies, resulting in distinct
      outcomes and illustrating that APROBA-Plus could serve as a standard extension of
      routine risk assessments. By visualizing the uncertainties, APROBA-Plus provides
      a more transparent and informative outcome than the more usual deterministic
      approaches, so that risk managers can make better informed decisions. For
      example, APROBA-Plus can help in deciding whether risk-reducing measures are
      warranted or that a refined risk assessment would first be needed. If the latter,
      the tool can be used to prioritize possible refinements. APROBA-Plus may also be
      used to rank substances into different risk categories, based on potential health
      risks without being compromised by different levels of conservatism that may be
      associated with point estimates of risk.

PMID- 29074419
TI  - Should Hemodynamic Guidance for Treatment of Acute Decompensated Heart Failure be
      Driven by the Right?

PMID- 29074417
TI  - Multiple mechanisms underlying neuroprotection by secretory phospholipase A2
      preconditioning in a surgically induced brain injury rat model.
AB  - BACKGROUND: Intra-operative bleeding, post-operative brain edema and
      neuroinflammation are major complications in patients with surgical brain injury
      (SBI). Phospholipase A2 (PLA2) is the upstream enzyme which initiates the PLA2, 5
      lipoxygenase (5-LOX) and leukotriene B4 (LTB4) inflammatory pathway. We
      hypothesized PLA2preconditioning (PPC) prior to SBI can activate endogenous anti
      inflammatory responses to protect against SBI. This study evaluated if PPC can
      ameliorate neurosurgical complications and elucidated PPC-mediated possible
      protective mechanisms in a rat SBI model. METHODS: Total 105 adult male Sprague
      Dawley rats were used for this study. SBI was induced by partial resection of the
      right frontal lobe. PLA2 or 0.9% NaCl was injected via rats' tail vein for 3
      consecutive days prior to SBI. For mechanism study, a selective PLA2 inhibitor,
      Manoalide and 5-LOX inhibitor, Zileuton were injected intravenously with PPC to
      elucidate the role of PLA2 and 5-LOX in PPC-mediated anti-inflammatory effects.
      Brain water content (BWC) and lung water content, neurological tests, ELISA,
      western blot, immunohistochemistry, white blood cells (WBC) count, and
      spectrophotometric assay for intra-operative hemorrhage volume were evaluated.
      RESULTS: First, PPC reduced brain water content, intra-operative bleeding, and
      improved neurological function after SBI. Second, PPC decreased 5-LOX expression
      and brain leukocyte infiltration, while increasing glial fibrillary acidic
      protein (GFAP) expression in the peri-resection brain tissue after SBI. Third,
      PPC induced peripheral inflammation represented by mild pulmonary inflammation
      and increased peripheral blood WBC count and LTB4 level. Lastly, PPC increased
      blood glucose concentration and glucocorticoid levels after SBI. In addition, PPC
      mediated above-mentioned changes were partially reversed by administration of
      PLA2 inhibitor, Manoalide and 5-LOX inhibitor, Zileuton. CONCLUSIONS: PPC
      conferred neuroprotection against SBI via multi-target involvement induced anti
      inflammatory mechanisms.

PMID- 29074420
TI  - Effect of Tranexamic Acid on Prevention of Hemorrhagic Mass Growth in Patients
      with Traumatic Brain Injury.
AB  - BACKGROUND: Intracranial hemorrhage is a common complication of traumatic brain
      injury (TBI). The purpose of this study is evaluation of the effect of tranexamic
      acid (TXA) on hemorrhagic mass growth in TBI patients. PATIENTS AND METHODS: In
      this randomized, double-blind clinical trial, 149 patients with TBI and any kind
      of blood on their computed tomography scan enrolled in the study and were
      randomly allocated to receive TXA or placebo. After 24 hours, computed tomography
      scan was repeated for assessing the changes in hemorrhage, new bleeding, and mass
      effects of blood on brain tissue. The primary outcome was growth of the
      hemorrhagic lesion. Data were analyzed by SPSS software using Fisher exact, chi
      square, and Mann-Whitney U tests, as well as linear and logistic regression
      models. FINDINGS: The incidence of hemorrhagic lesion growth was 20.5% in the TXA
      group and 22.7% in the placebo group. The difference was not significant (P =
      0.87, RR = 0.89). The mean (standard deviation) of hemorrhagic lesion growth was
      9.4 (15.3) in the TXA group and 10.2 (10.1) in the placebo group without
      significant difference (P = 0.27). The frequency of deaths (2.7% vs. 4%), adverse
      outcome at discharge (10.8% vs. 17.3%), and 3 months later (6.8% vs. 14.7%) in
      the TXA group were lower than the placebo, but the difference was not
      statistically significant. No side effect was observed with the administration of
      TXA. CONCLUSION: Administration of a short dose of TXA does not lead to
      significant prevention of growth of posttraumatic hemorrhagic lesion or
      improvement of clinical outcomes.

PMID- 29074421
TI  - Long-Term Efficacy of Initial Microvascular Decompression Versus Subsequent
      Microvascular Decompression for Idiopathic Hemifacial Spasm.
AB  - OBJECTIVE: Hemifacial spasm (HFS) is a disorder characterized by intermittent,
      involuntary facial muscle contractions. Microvascular decompression (MVD) is the
      gold treatment for HFS. The aim of this research was to discuss whether patients
      undergoing MVD as their initial surgical intervention experience greater spasm
      control than patients experiencing an MVD performed as a subsequent surgical
      intervention. METHODS: The study included 976 patients with HFS, 452 of whom
      (group A) underwent MVD as their initial surgical intervention and 524 of whom
      (group B) underwent subsequent MVD. Relevant clinical data including outcome of
      MVD, operative findings, complications, and so on were collected immediately
      after MVD operation and at follow-up. RESULTS: The follow-up period was 7-9 years
      (mean, 7.96 +/- 0.87 years). The mean age at intervention was 53.14 years and
      55.43 years in the 2 groups, respectively. The long-term postoperative relief
      rate of patients in the 2 groups was 98.23% and 87.21%, respectively. There was a
      significant difference in long-term postoperative relief rate of patients between
      the 2 groups (P < 0.05). CONCLUSIONS: Patients undergoing MVD for HFS as the
      primary treatment experience better long-term efficacy than patients first
      treated with botulinum neurotoxin type A.

PMID- 29074422
TI  - Suboccipital Craniotomy Versus Craniectomy: A Survey of Practice Patterns.
AB  - OBJECTIVE: Open surgical access to the posterior fossa traditionally has been
      achieved by permanent bone removal and remains the mainstay of posterior fossa
      surgery, although craniotomy is an alternative. Considerable variation exists at
      both the national and international levels within a variety of neurologic and
      neurosurgical disciplines. In this study, we surveyed current practice patterns
      regarding preference of suboccipital craniotomy or craniectomy. METHODS: The
      membership directory of the American Academy of Neurological Surgeons was
      reviewed. SurveyMonkey was used to distribute the survey to members of the
      American Academy of Neurological Surgeons via a modified Dillman method for e
      mail correspondence. Comparisons of frequency distributions, means, and medians,
      as well as multiple logistic regression were used to determine surgical
      preferences for craniotomy versus craniectomy. RESULTS: We received 1102
      responses (19.6%). Overall, 542 (49.7%) respondents prefer craniotomy and 548
      (50.3%) prefer craniectomy. Respondents who prefer craniotomy had completed a
      residency more recently than respondents who preferred craniectomy (15.9 vs. 21.1
      years, P < 0.0001) and were more likely to practice outside of North America (P <
      0.01). Some 81.4% of pediatric neurosurgeons prefer craniotomy compared with
      43.6% of adult neurosurgeons (P < 0.0001). Craniotomy was most highly preferred
      for tumor resection and vascular malformation. Within the United States, there
      was significant variation in preference for craniotomy based on geographic
      region, with New England most commonly preferring craniotomy and the Mid-Atlantic
      region most commonly preferring craniectomy. CONCLUSIONS: Our results show that
      preference for suboccipital craniotomy or craniectomy varies according to
      geographic location of practice, time since completing residency, and age of
      patient population.

PMID- 29074423
TI  - Percutaneous Endoscopic Lumbar Reoperation for Recurrent Sciatica Symptoms: A
      Retrospective Analysis of Outcomes and Prognostic Factors in 94 Patients.
AB  - BACKGROUND: Recurrent symptoms of sciatica after previous surgical intervention
      is a relatively common and troublesome clinical problem. Percutaneous endoscopic
      lumbar decompression has been proved to be an effective method for recurrent
      lumbar disc herniation. However, the prognostic factors and outcomes of
      percutaneous endoscopic lumbar reoperation (PELR) for recurrent sciatica symptoms
      were still unknown. The purpose of this study was to evaluate the outcomes and
      prognostic factors of patients who underwent PELR for recurrent sciatica
      symptoms. METHODS: From 2009 to 2015, 94 patients who underwent PELR for
      recurrent sciatica symptoms were enrolled. The primary surgeries include
      transforaminal lumbar interbody fusion (n = 16), microendoscopic discectomy (n =
      31), percutaneous endoscopic lumbar decompression (PELD, n = 17), and open
      discectomy (n = 30). The mean follow-up period was 36 months, and 86 (91.5%)
      patients had obtained at least 24 months' follow-up. RESULTS: Of the 94 patients
      with adequate follow-up, 51 (54.3%) exhibited excellent improvement, 23 (24.5%)
      had good improvement, and 7 (7.4%) had fair improvement according to modified
      Macnab criteria. The average re-recurrence rate was 9.6%, with no difference
      among the different primary surgery groups (PELD, 3/17; microendoscopic
      discectomy, 2/31; open discectomy, 3/30; transforaminal lumbar interbody fusion,
      1/16). There was a trend toward greater rates of symptom recurrence in the
      primary group of PELD who underwent percutaneous endoscopic lumbar reoperation
      compared with other groups, but this did not reach statistical significance (P >
      0.05). Multivariate analysis suggested that age, body mass index, and surgeon
      level was independent prognostic factors. Obesity (hazard ratio 13.98, 95%
      confidence interval 3.394-57.57; P < 0.001) was the risk factor affecting re
      recurrence according to logistic regression analysis. CONCLUSIONS: PELR is a safe
      and effective treatment for recurrent sciatica symptoms regardless of different
      primary operation type. Obesity, inferior surgeon level, and patient age older
      than 40 years were associated with a worse prognosis. Obesity was also a strong
      and independent predictor of re-recurrence sciatica symptoms after percutaneous
      endoscopic lumbar decompression.

PMID- 29074424
TI  - Effect of Baroreceptor Sensitivity on Outcomes in Patients with Acute Spontaneous
      Intracerebral Hemorrhage.
AB  - BACKGROUND: Reduced baroreflex sensitivity (BRS) has been reported in patients
      with acute cardiovascular events. We tested the hypothesis that BRS is
      substantially reduced in patients with spontaneous intracerebral hemorrhage (ICH)
      and that BRS can predict treatment outcomes. METHODS: We examined BRS and other
      cardiovascular autonomic parameters in 35 patients with ICH over the course of 30
      days. Cardiovascular autonomic parameters also were evaluated in 30 healthy
      volunteer subjects during the study period. Outcome was assessed at 30 days with
      the modified Rankin Scale (mRS). Good outcome was defined as an mRS <1, whereas
      patients defined as having a poor outcome had either an mRS >=2 or died shortly
      after the stroke event. RESULTS: Twenty patients had a poor outcome, and 15
      patients had a good outcome. BRS values in the patients with poor outcome group
      were lower in comparison with the healthy subjects, and BRS values in patients
      with poor outcomes were significantly lower than that those in patients with good
      outcomes on day 1, day 4, and day 10. BRS was associated independently with
      outcome and the cut-off value of BRS on day 1 in the poor outcome group was 6.79.
      CONCLUSIONS: Based on our results, BRS value at admission is a more powerful
      predictor of outcome than the Glasgow Coma Scale score at admission. An assay of
      BRS could be added as a biomarker for outcome prediction among patients with
      spontaneous ICH in clinical practice.

PMID- 29074425
TI  - The membrane bile acid receptor TGR5 drives cell growth and migration via
      activation of the JAK2/STAT3 signaling pathway in non-small cell lung cancer.
AB  - Mounting evidence suggests that an emerging G protein-coupled receptor, TGR5,
      plays a crucial role ranging from metabolic diseases to cancers. However, the
      biological functions of TGR5 in non-small cell lung cancer (NSCLC) remain
      elusive. We found that TGR5 was aberrantly expressed in NSCLC and positively
      correlated with an advanced clinical stage in NSCLC patients. We further
      discovered that TGR5 knockdown prevented JAK2 and STAT3 phosphorylation and
      repressed the expression of STAT3 target genes, thus inhibiting cell
      proliferation, migration and invasion in NSCLC. Moreover, the promotive effects
      of TGR5 were significantly reversed by a JAK2 inhibitor or STAT3 knockdown.
      Additionally, we demonstrated a positive correlation between TGR5 and p-STAT3
      expression in NSCLC tissue samples. Patients with both high TGR5 and p-STAT3
      expression had the worst prognosis. In addition, the serum levels of deoxycholic
      acid (DCA), ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in NSCLC
      patients were much higher than those in the healthy controls and the patients
      with higher serum DCA levels had stronger TGR5 expression simultaneously.
      Moreover, DCA markedly promoted NSCLC cell migration and invasion through a TGR5
      dependent way. Taken together, these results indicate that TGR5 drives cell
      growth and migration through JAK2/STAT3 signaling pathway in NSCLC.

PMID- 29074426
TI  - Survival of the fittest: Cancer challenges T cell metabolism.
AB  - T cells represent the major contributors to antitumor-specific immunity among the
      tumor-infiltrating lymphocytes. However, tumors acquire ways to evade
      immunosurveillance and anti-tumor responses are too weak to eradicate the
      disease. T cells are often functionally impaired as a result of interaction with,
      or signals from, transformed cells and the tumor microenvironment, including
      stromal cells. Among these, nutrients use and consumption is critically important
      for the control of differentiation and effector mechanisms of T cells. Moreover,
      Treg cells-skewing conditions often coexist within the cancer milieu, which
      sustains the notion of immune privileged tumors. Additionally, cancer cells
      contend with tumor infiltrating lymphocytes for nutrients and can outcompete the
      immune response. PD1- and CTLA-based immunotherapies partially remodel cell
      metabolism leading the way to clinical approaches of metabolic reprogramming for
      therapeutic purposes. Here we shortly discuss T cell fates during anti-tumor
      immune responses and how signals within tumor microenvironment influence T cell
      metabolism, altering functions and longevity of the cell.

PMID- 29074427
TI  - Invasive properties of Ralstonia solanacearum virulent and avirulent strains in
      tomato roots.
AB  - Ralstonia solanacearum causes bacterial wilt disease in a wide range of host
      plants, including tomato. To elucidate the invasion pattern of R. solanacearum,
      one avirulent strain, FJAT-1458, and one virulent strain, FJAT-91, were
      characterized according to their colonization and interaction with host in tomato
      roots. Both strains colonized in tomato roots. The highest colonization numbers
      were 1.66 * 108 cfu g-1 by FJAT-91 at 5 days (d) after inoculation and 1.09 * 108
      cfu g-1 by FJAT-1458 at 6 d after inoculation. Infection with FJAT-91 caused
      tomato plant wilt with a disease index of 23.65% at 3 d after inoculation and
      100% at 6 d after inoculation, and infection with FJAT-1458 did not cause plant
      wilt. Compared with FJAT-1458, infection with FJAT-91 reduced elongation of
      tomato roots, induced serious browning, and overflowed bacteria during the late
      stages of infection. Examination of cellular structure showed that infection with
      FJAT-1458 did not have obvious destructive effects on plant cells, while FJAT-91
      induced a series of cytopathological changes, including swelling of mitochondria,
      degeneration of cytoplasm and nuclear heterochromatin, and collapse of host
      cells, which eventually resulted in the death of the host plant. The
      cytopathological changes appeared from the second to the fourth disease stages.

PMID- 29074428
TI  - Identification and function analysis of canine stimulator of interferon gene
      (STING).
AB  - Stimulator of interferon gene (STING) plays an important role in the cyclic GMP
      AMP synthase (cGAS)-mediated activation of type I IFN responses. In this study,
      we identified and cloned canine STING gene. Full-length STING encodes a 375 amino
      acid product that shares the highest similarity with feline STING. Highest levels
      of mRNA of canine STING were detected in the spleen and lungs while the lowest
      levels in the heart and muscle. Analysis of its cellular localization showed that
      STING is localizes to the endoplasmic reticulum. STING overexpression induced the
      IFN response via the IRF3 and NF-kappaB pathways and up-regulated the expression
      of ISG15 and viperin. However, knockdown of STING did not inhibit the IFN-beta
      response triggered by poly(dA:dT), poly(I:C), or SeV. Finally, overexpression of
      STING significantly inhibited the replication of canine influenza virus H3N2.
      Collectively, our findings indicate that STING is involved in the regulation of
      the IFN-beta pathway in canine.

PMID- 29074429
TI  - Outer membrane protein A: An immunogenic protein induces highly protective
      efficacy against Vibrio ichthyoenteri.
AB  - Vibrio ichthyoenteri was an important causative agent of bacterial enteritis in
      flounder (Paralichthys olivaceus). Outer membrane protein A (OmpA) of Gram
      negative pathogen was a major cell surface antigen. In the present study, OmpA of
      V. ichthyoenteri was recombinantly expressed in Escherichia coli, and the
      immunogenicity of OmpA was identified by western blotting using flounder anti
      rOmpA and anti-V. ichthyoenteri antibodies. The vaccine potential of rOmpA was
      tested in a flounder model, and a high relative percentage of survival rate was
      obtained with 73.1% after challenge with V. ichthyoenteri. Meanwhile, the immune
      response of flounder induced by rOmpA was also investigated, and the results
      showed that the sIg + lymphocytes in blood, spleen, and pronephros significantly
      proliferated, and the peak levels occurred at week 4 after immunization.
      Moreover, rOmpA could induce higher levels of specific serum antibodies than the
      control group after immunization, and the peak level occurred at week 5 after
      immunization. Meanwhile, qRT-PCR analysis showed that the expressions of CD4-1,
      CD8alpha, IL-1beta, IFN-gamma, MHCIalpha and MHCIIalpha genes were significantly
      up-regulated after immunization with rOmpA. Taking together, these results
      demonstrated that rOmpA could evoke highly protective effects against V.
      ichthyoenteri challenge and induce strong immune response of flounder, which
      indicated that OmpA was a promising vaccine candidate.

PMID- 29074431
TI  - Antagonistic studies and hyphal interactions of the new antagonist Aspergillus
      piperis against some phytopathogenic fungi in vitro in comparison with
      Trichoderma harzianum.
AB  - The present study represents, for the first time, the detailed studies about the
      hyphal interactions of Aspergillus piperis, as a new antagonist, against some
      isolated plant pathogenic fungi (Alternaria alternata, Alternaria solani,
      Botrytis cinerea, Sclerotium cepivorum and Sclerotinia sclerotiorum) in vitro.
      The bio-controlling capability of A. piperis against the tested phytopathogens
      was tested using the dual culture method. This experiment revealed that A.
      piperis had antagonistic activity and reduced the growth of the tested
      phytopathogens and grew over their mycelia in the paired plates. Also, several
      antagonistic mechanisms were recorded, in this study, between A. piperis and the
      tested phytopathogens using the microscopic examination. The bio-controlling
      activity and the antagonistic mechanisms exhibited by the new antagonist, A.
      piperis were compared with those obtained by the common antagonist, Trichoderma
      harzianum against the same phytopathogens. The obtained results showed that, A.
      piperis was more effective than T. harzianum in inhibiting all the tested species
      in the dual culture plates. The best result was 81.85% inhibition percentage
      against S. sclerotiorum by A. piperis while, T. harzianum exhibits only 45.18%.
      Moreover, several antagonistic mechanisms and hyphal interactions were
      investigated among the hyphae of both A.piperis and T. harzianum and the hyphae
      of the tested phytopathogens. These mechanisms were summarized as; mycoparasitism
      (coiling and penetration of the hyphae) and antibiosis in the form of lysis of
      the hyphal cells and spores, denaturation and breaking of the hyphae. The
      indirect interaction (antibiosis) and the direct mycoparasitism were observed by
      A. piperis against all the tested phytopathogens, but it attacked the hyphae and
      conidiophores of A. alternata by only the antibiosis interaction. The microscopic
      examination revealed also that T. harzianum attacked the tested phytopathogens by
      both antibiosis and mycoparasitism except against A. solani which attacked only
      by mycoparasitism.

PMID- 29074430
TI  - Role of Th17 and Treg cells in septic arthritis and the impact of the Th17/Treg 
      derived cytokines in the pathogenesis of S. aureus induced septic arthritis in
      mice.
AB  - Intravenous inoculation of Swiss mice with S. aureus leads to severe synovial
      joint tissue swelling along with prominent T lymphocyte infiltrate with
      associated inflammation in synovial tissue. Cytokines released from macrophages
      such as TNF-alpha, IL-1beta and IL-6 the main players that precede cartilage and
      bone destruction during septic arthritis (SA) followed by osteoclast
      differentiation and bone resorption. CD4+ naive T cells upon cytokine driven
      activation, differentiate into lineages of helper (Th) and regulatory T cells
      (Treg) including inflammatory Th17 cell lineage. Acting as counterbalance, Tregs
      protect the host by releasing anti-inflammatory IL-10. A disturbed balance
      between Th17 and Treg cell development skews the pathways towards Th17 lineage,
      but how it actually induces SA is still unexplored. Therefore, this study has
      been attempted to demonstrate the Th17/Treg ratio in synovial tissue, spleen and
      peripheral blood by FACS and their derived cytokines from serum of arthritic
      mice. Here, we reported that the ratios of Th17/Treg as well as their related
      cytokine levels were increased at 3 days post-infection which was decreased
      during 9 DPI but heightened again at 15DPI resulting in persistence of the
      disease, though decreased again at 30 DPI even in animals with increased dose of
      infection. Bacterial colonies were present in synovial joints at 15 DPI in
      animals with increased infection but found to be absent at 30 DPI. Maintaining
      Th17/Treg balance by neutralizing functionally active Th17 and their related
      cytokines or adoptive transfer of fully active Tregs and/or their related
      cytokines may lead to a novel therapeutic strategy for combating Staphylococcal
      arthritis.

PMID- 29074432
TI  - Healthcare workers' hands as a vehicle for the transmission of virulent strains
      of Candida spp.: A virulence factor approach.
AB  - BACKGROUND: Although the majority of Candida infections are thought to come from
      endogenous sources, the healthcare workers' (HCWs) hands are being increasingly
      reported as vehicles for the transmission of pathogens. The aim of the present
      study was to evaluate the susceptibility of yeast isolated from the HCWs' hands
      and ICU (Intensive Care Unit) surfaces to antifungal agents and to determine the
      virulence potential and the genetic similarity between the same. METHODS: The
      susceptibility of yeasts from the HCWs' hands (n = 57) and ICU surfaces (n = 98)
      to conventional antifungals (fluconazole, voriconazole, amphotericin B and
      micafungin) was evaluated using the broth microdilution assay accordance with
      CLSI M27-A3. Additionally, some virulence factors such as adhesion and biofilm
      capacity on abiotic surfaces and on endothelial cells were evaluated, as well as
      germ tube formation. The similarity among yeast isolates were evaluated by the
      RAPD technique using the P4, OPA18 and OPE18 primers. RESULTS: Five species of
      Candida were found on the HCWs' hands (C. albicans, C. parapsilosis (sensu
      stricto), C. glabrata, C. tropicalis and C. krusei) and two on ICU surfaces (C.
      albicans and C. parapsilosis (sensu stricto)). The isolates from hands had higher
      resistance rates, with C. glabrata having the highest indices (100% FLU; 100%
      MFG). The similarity of C. albicans from HCWs and ICU surfaces was >=80%
      according to the three primers analyzed. Candida spp. from hands had a greater
      potential for adhesion and biofilm formation on abiotic surfaces (p < 0.05). C.
      albicans from ICU surfaces had the greatest potential of adhesion on endothelial
      cells after 2 and 24 h, and presented high filamentation in SEM images and formed
      more and larger germ tubes (p < 0.05). CONCLUSION: the present study showed the
      significant virulence potential of yeasts transmitted in the hospital environment
      for the first time. Additionally, healthy people working in the ICU can carry
      these yeasts, which are capable of surviving in hospital surfaces, on their
      hands, offering a risk to patients, especially those who are immunocompromised.

PMID- 29074433
TI  - A novel cationic cobalt(III) Schiff base complex: Preparation, crystal structure,
      Hirshfeld surface analysis, antimicrobial activities and molecular docking.
AB  - A novel Co(III) complex, [Co(L)(Imi)3]Cl incorporating 2-((3-methoxy-2
      oxidobenzylidene)amino)-4-methylphenolate (L2-), as a dibasic deprotonated Schiff
      base ligand and imidazole (Imi) was synthesized and fully characterized using
      physicochemical and spectroscopic techniques including elemental analysis,
      conductance measurement, FT-IR, UV-Vis and X-ray single crystal diffraction. As
      the conductivity data showed, the synthesized complex had a 1:1 ionic nature. The
      structure of the complex was found to be distorted octahedral in which, O/N donor
      atoms of the Schiff base ligand and N atoms of three imidazole groups were
      involved. Antimicrobial activity of the Co(III) complex as well as the its parent
      Schiff base ligand against two Gram-positive bacteria (S. Aureus and M. luteus),
      two Gram-negative bacteria (E. coli and P. aeruginosa) and a fungus (C. Albicans)
      was studied. Moreover, the antimicrobial activity of [Co(L)(Imi)3]Cl was
      investigated using molecular docking of the complex with GlcN-6-P synthase.

PMID- 29074434
TI  - Antifungal activity and patterns of N-acetyl-chitooligosaccharide degradation via
      chitinase produced from Serratia marcescens PRNK-1.
AB  - Serratia marcescens PRNK-1, which has strong chitinolytic activity, was isolated
      from cockroaches (Periplaneta americana L.). The chitinase from S. marcescens
      PRNK-1 was characterized after incubation in a 0.5% colloidal chitin medium at 30
      degrees C for 3 days. The molecular weights of three bands after staining for
      chitinase activity were approximately 34, 41, and 48 kDa on an SDS-PAGE gel. S.
      marcescens PRNK-1 strain strongly inhibited hyphal growth of Rhizoctonia solani
      and Fusarium oxysporum. Thin-layer chromatography (TLC) and high performance
      liquid chromatograph (HPLC) analyses were conducted to investigate the
      degradation patterns of N-acetyl-chitooligosaccharides by PRNK-1 chitinase. The N
      acetyl-chitooligosaccharides: N-acetyl-chitin dimer (GlcNAc)2, N-acetyl-chitin
      trimer (GlcNAc)3, and N-acetyl-chitin tetramer (GlcNAc)4 were degraded to
      (GlcNAc)1-3 on a TLC plate. In an additional experiment, (GlcNAc)6 was degraded
      to (GlcNAc)1-4 on a TLC plate. The optimal temperature for chitinase activity of
      the PRNK-1 was 50  degrees C, producing 32.8 units/mL. As seen via TLC, the
      highest degradation of (GlcNAc)4 by PRNK-1 chitinase occurred with 50  degrees C
      incubation. The optimal pH for chitinase activity of PRNK-1 was pH 5.5, producing
      24.6 units/mL. As seen via TLC, the highest degradation of (GlcNAc)4 by PRNK-1
      chitinase occurred at pH 5.0-6.0. These results indicate that chitinase produced
      from S. marcescens PRNK-1 strain showed strong antifungal activity and potential
      of production of N-acetyl-chitooligosaccharides.

PMID- 29074435
TI  - The natural compound magnolol affects growth, biofilm formation, and
      ultrastructure of oral Candida isolates.
AB  - The incidence of oral candidosis has increased in recent years due to the
      escalation in HIV-infection, cancer treatments, organ transplantation, and
      diabetes. In addition, corticosteroid use, dentures, and broad-spectrum
      antibiotic use have also contributed to the problem. Treatment of oral candidosis
      has continued to be problematic because of the potential toxicity of antifungals
      in clinical use, and, above all, development of drug resistance among patients.
      In this study, the antifungal effect of magnolol was investigated against 64
      strains of Candida spp. (four standard and 60 oral isolates) through minimum
      inhibitory concentration (MIC) and growth curve assays. Insight into the
      mechanisms of the antifungal action has been gained through ultrastructural
      studies using confocal scanning laser microscopy (CSLM), scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). Molecular docking
      was done for predicting the interactions of magnolol with ergosterol at
      supramolecular level. The toxicity of magnolol on human erythrocytes was measured
      by in vitro hemolytic assay. MIC values of magnolol ranged from 16-64 MUg/ml,
      respectively. All tested isolates showed a marked sensitivity towards magnolol in
      growth curve assays. Biofilm results suggested that magnolol showed strong anti
      biofilm activity. The results obtained for four different Candida spp.
      demonstrated that MBIC values of magnolol showed the average biofilm inhibition
      by 69.5%, respectively. CLSM experiments showed that cells exposed to magnolol
      (MIC) exhibited cell membrane disruption. SEM analysis of magnolol treated cells
      resulted in deformed cells. TEM micrographs showed rupturing of the cell wall and
      plasma membrane, releasing the intracellular content, and swelling of the cell
      wall. Hemolytic activity of magnolol is 11.9% at its highest MIC compared to an
      activity level of 25.4% shown by amphotericin B (Amp B) at 1 MUg/ml. Lipinski's
      parameters calculated for magnolol suggested its good oral bioavailability.
      Docking studies indicated that magnolol might be interacting with ergosterol in
      the fungal cell membranes. Together, the present study provides enough evidence
      for further work on magnolol so that better strategies could be employed to treat
      oral candidosis.

PMID- 29074436
TI  - DHPAC, a novel synthetic microtubule destabilizing agent, possess high anti-tumor
      activity in vincristine-resistant oral epidermoid carcinoma in vitro and in vivo.
AB  - Multidrug resistance (MDR) is one of major obstacles to effective
      chemotherapeutic treatment of cancer. This study showed that DHPAC, 2-(6-ethoxy-3
      (3-ethoxyphenylamino) -1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy)
      acetamide, a novel compound that binds to the same site on microtubules as
      colchicine, has high anti-tumour activity in vincristine-resistant oral
      epidermoid carcinoma (KB/V) cells. It found that the presence of DHPAC strongly
      inhibited KB/V cell growth in vivo and in mice xenograft. The inhibitory effect
      of DHPAC is much stronger than that by colchicine in these KB/V cells (IC50:
      64.4nM and 458.0nM respectively). Treatment of the cells with DHPAC induced cell
      apoptosis by reducing mitochondrial membrane potential and altered the expression
      of several apoptosis-related proteins such as Bcl-2, Bax, Caspase-9, Cytochrome c
      and PARP. DHPAC treatment also caused cell rest in G2/M phase by regulating of
      the expression of a number of cell cycle-related proteins (e.g. Cyclin B1, Cdc2,
      Cdc25b, Cdc25c, RSK2). Furthermore, DHPAC presence inhibits PTEN phosphorylation
      and PTEN/Akt/NF-kappaB signalling. Thus, DHPAC has potent anti-cancer activity in
      MDR tumuors and may be a potential therapeutic agent for the treatment of
      vincristine-resistant human oral epidermoid carcinoma.

PMID- 29074437
TI  - Metabolomics applied to diabetes-lessons from human population studies.
AB  - The 'classical' distribution of type 2 diabetes (T2D) across the globe is rapidly
      changing and it is no longer predominantly a disease of middle-aged/elderly
      adults of western countries, but it is becoming more common through Asia and the
      Middle East, as well as increasingly found in younger individuals. This global
      altered incidence of T2D is most likely associated with the spread of western
      diets and sedentary lifestyles, although there is still much debate as to whether
      the increased incidence rates are due to an overconsumption of fats, sugars or
      more generally high-calorie foods. In this context, understanding the
      interactions between genes of risk and diet and how they influence the incidence
      of T2D will help define the causative pathways of the disease. This review
      focuses on the use of metabolomics in large cohort studies to follow the
      incidence of type 2 diabetes in different populations. Such approaches have been
      used to identify new biomarkers of pre-diabetes, such as branch chain amino
      acids, and associate metabolomic profiles with genes of known risk in T2D from
      large scale GWAS studies. As the field develops, there are also examples of meta
      analysis across metabolomics cohort studies and cross-comparisons with different
      populations to allow us to understand how genes and diet contribute to disease
      risk. Such approaches demonstrate that insulin resistance and T2D have far
      reaching metabolic effects beyond raised blood glucose and how the disease
      impacts systemic metabolism.

PMID- 29074438
TI  - 3D nerve cell cultures and complex physiological relevance.
AB  - The field of tissue engineering has not yet provided knowledge on which a
      consensus for the complex physiological relevance (CPR) of neuronal cultures
      could be established. The CPR of 3D neuronal cultures can have a profound impact
      on the drug discovery process through the validation of in vitro models for the
      study of neuropsychiatric and degenerative diseases, as well as screening for
      neurotoxicity during drug development. Herein, we assemble evidence in support of
      the potential of [Ca2+]i oscillation frequency as a CPR outcome that can
      demonstrate the in vivo-like behavior of 3D cultures and differentiate them from
      2D monolayers. We demonstrate that [Ca2+]i oscillation frequencies in 2D cultures
      are significantly higher than those found in 3D cultures, and provide a possible
      molecular explanation.

PMID- 29074439
TI  - Gemcitabine and glioblastoma: challenges and current perspectives.
AB  - Gemcitabine is a nucleoside analog currently used for the treatment of various
      solid tumors as a single agent or in combination with other chemotherapeutic
      drugs. Its use against highly aggressive brain tumors (glioblastoma) has been
      evaluated in preclinical and clinical trials leading to controversial results.
      Gemcitabine can inhibit DNA chain elongation, is a potent radiosensitizer and it
      can enhance antitumor immune activity, but it also presents some drawbacks (e.g.,
      short half-life, side effects, chemoresistance). The aim of this review is to
      discuss the challenges related to the use of gemcitabine for glioblastoma and to
      report recent studies that suggest overcoming these obstacles opening new
      perspectives for its use in the field (e.g., gemcitabine derivatives and/or
      nanomedicines).

PMID- 29074440
TI  - Microarray patches: potentially useful delivery systems for long-acting
      nanosuspensions.
AB  - Long-acting drug nanosuspension formulations are coming to the fore as controlled
      release strategies for several medical conditions and as a preventative measure
      against HIV infection. However, such delivery systems must, by necessity, be
      given by hypodermic injection, typically into muscle. This poses problems for
      patients who are needle-phobic, given that injections have to be administered on
      a weekly or monthly basis. Needle-stick injuries, inappropriate reuse of needles,
      and poor disposal practices are major challenges in developing countries.
      Dissolving microneedles (MNs) are capable of delivering high drug doses, if
      suitably designed and formulated, and are also capable of delivering
      nanoparticles (NPs) into viable skin. Given that such microneedles are minimally
      invasive and self-disabling, the potential for major enhancement in patient care
      and compliance exists. In this review, we explore the key considerations in the
      development of these combination drug delivery systems.

PMID- 29074443
TI  - Posterior belly of digastric muscle flap for contour deformity correction after
      superficial parotidectomy.
AB  - The correction of the contour deformity after parotidectomy has become an
      essential procedure in the recent times for the betterment of patients' quality
      of life. Various modalities have been highlighted in the literature for the same.
      We recommend the use of posterior belly of digastric muscle flap for correction
      of contour deformity post excision of parotid gland tumors, subsequently
      ameliorating the aesthetics of the face.

PMID- 29074441
TI  - Marketing authorisation of orphan medicines in Europe from 2000 to 2013.
AB  - An analysis was performed on a data set of 157 orphan designated medicines with
      an outcome for marketing authorisation application (MAA) between 2000 and 2013.
      The intention was to understand the factors associated with marketing
      authorisation success, the challenges developers face regarding orphan medicine
      development, and how scientific advice (SA) is used during development. The
      results demonstrated that orphan medicines have a lower success rate compared
      with non-orphan medicines and that determinants for marketing authorisation
      success were company size and compliance with SA. Compliance with SA could help
      orphan medicine developers overcome clinical development challenges.

PMID- 29074442
TI  - Conservative management of an atypical intra-sinusal ossifying fibroma associated
      to an aneurysmal bone cyst.
AB  - Ossifying fibroma (OF) is a benign fibro-osseous lesion mainly occurring in young
      adults and seems to originate from the periodontal ligament. Aneurysmal bone cyst
      (ABC) is a benign intraosseous lesion characterized by blood-filled spaces of
      various sizes. These two lesions can specifically affect the jaws and are
      commonly described in the literature. However, few cases describing an
      association of OF and ABC have been reported in the literature, especially in the
      maxillary sinus. We report the case of a 40-year-old male patient affected with
      an asymptomatic lesion with a dual component of OF and ABC laying in the
      maxillary sinus. Our aim is to discuss its clinical and morphological features as
      well as treatment results.

PMID- 29074444
TI  - Porcine abdominal cutaneous flap model: A simple and reliable method.
AB  - The increase of reconstructive microsurgery procedures leads to the development
      of various technologies. Before being validated in human clinical studies, these
      technologies and devices need to be validated on animal models. We present a
      simple, reliable and reproducible model of a cutaneous flap in pigs. This flap is
      pedicled on the superficial inferior epigastric pedicle (SIEP). The surgical
      technique is described. This flap can be buried and, if necessary, harvested on
      both sides. It did not alter the abdominal wall, and so it has allowed painless
      long-term follow-up of the animals. To our knowledge, this technique has never
      been reported in pigs.

PMID- 29074445
TI  - Fibrous condylar dysplasia: Resection and reconstruction with a custom-made TMJ
      prosthesis using virtual surgical planning.
AB  - The main objective of this article is to describe the indications for custom-made
      alloplastic reconstruction of the temporomandibular joint (TMJ) using the new
      techniques of virtual surgical planning and computer-aided design/computer-aided
      manufacturing (CAD/CAM) technology through the study of a clinical case and an
      updated review of the literature. The patient was a 45-year-old male with a fast
      growing condylar dysplasia that produced a progressive facial deformity with
      limited mandibular mobility, which required a radical resection. Predictable,
      satisfactory, and stable results over time are described from the aesthetic,
      functional, and symptomatic points of view, through a comprehensive approach to
      all the aspects of this case by following an appropriate line of development and
      using the most current techniques.

PMID- 29074447
TI  - AGA White Paper: Optimizing Endoscopic Ultrasound-Guided Tissue Acquisition and
      Future Directions.

PMID- 29074448
TI  - Patient-Reported Outcome Measures for Use in Clinical Trials and Clinical
      Practice in Inflammatory Bowel Diseases: A Systematic Review.
AB  - BACKGROUND & AIMS: Mucosal inflammation must be carefully monitored to improve
      the long-term outcomes of patients with inflammatory bowel diseases (IBD).
      Patient-reported outcome measures (PROMs) are used increasingly to monitor
      disease activity in clinical practice and as endpoints in clinical trials. We
      performed a systematic review to provide an overview of the available PROMs on
      IBD activity and to evaluate their diagnostic value. METHODS: A systematic search
      of the PubMed, Medline, Cochrane library, and Embase databases using defined
      keywords, identified 973 articles. These were screened by 2 independent
      reviewers, and 37 articles on development or validation of PROMs to assess IBD
      activity were identified for further analysis. Based on the recommendations of
      the Food and Drug Administration (FDA), the following measurement properties were
      evaluated: content, construct, and criterion validity; reliability; and
      responsiveness to change. In addition, data on ease of use in clinical practice
      were collected. RESULTS: Seventeen articles presenting 20 different PROMs were
      included the final analysis, although none met all the FDA-recommended criteria.
      Only 2 PROMs (patient-reported Harvey Bradshaw Index and Simple Clinical Colitis
      Activity Index scores) reported patient involvement during its development. Only
      6 PROMs (patient-reported global assessment, patient assessment of disease
      activity, mobile health index for Crohn's disease, mobile health index for
      ulcerative colitis, patient-reported outcome derived from the Mayo score, and the
      6-point Mayo score) were validated as markers of IBD activity, using findings
      from endoscopy as the reference standard; these PROMs identified patients with
      mucosal inflammation with area under the curve values of 0.63-0.82. The mobile
      health index for CD and UC scores had the best measurement properties for use in
      clinical practice and in clinical trials. CONCLUSIONS: In a systematic review, we
      identified more than 20 PROMS that have been developed and tested for their
      ability to determine IBD activity. Further studies are needed to determine their
      accuracy and whether they can be used effectively in routine practice, clinical
      trials, telemedicine systems, and value-based healthcare programs.

PMID- 29074446
TI  - Efficacy and Safety of Digital Single-Operator Cholangioscopy for Difficult
      Biliary Stones.
AB  - BACKGROUND & AIMS: It is not clear whether digital single-operator cholangioscopy
      (D-SOC) with electrohydraulic and laser lithotripsy is effective in removal of
      difficult biliary stones. We investigated the safety and efficacy of D-SOC with
      electrohydraulic and laser lithotripsy in an international, multicenter study of
      patients with difficult biliary stones. METHODS: We performed a retrospective
      analysis of 407 patients (60.4% female; mean age, 64.2 years) who underwent D-SOC
      for difficult biliary stones at 22 tertiary centers in the United States, United
      Kingdom, or Korea from February 2015 through December 2016; 306 patients
      underwent electrohydraulic lithotripsy and 101 (24.8%) underwent laser
      lithotripsy. Univariate and multivariable analyses were performed to identify
      factors associated with technical failure and the need for more than 1 D-SOC
      electrohydraulic or laser lithotripsy session to clear the bile duct. RESULTS:
      The mean procedure time was longer in the electrohydraulic lithotripsy group
      (73.9 minutes) than in the laser lithotripsy group (49.9 minutes; P < .001).
      Ducts were completely cleared (technical success) in 97.3% of patients (96.7% of
      patients with electrohydraulic lithotripsy vs 99% patients with laser
      lithotripsy; P = .31). Ducts were cleared in a single session in 77.4% of
      patients (74.5% by electrohydraulic lithotripsy and 86.1% by laser lithotripsy; P
      = .20). Electrohydraulic or laser lithotripsy failed in 11 patients (2.7%); 8
      patients were treated by surgery. Adverse events occurred in 3.7% patients and
      the stone was incompletely removed from 6.6% of patients. On multivariable
      analysis, difficult anatomy or cannulation (duodenal diverticula or altered
      anatomy) correlated with technical failure (odds ratio, 5.18; 95% confidence
      interval, 1.26-21.2; P = .02). Procedure time increased odds of more than 1
      session of D-SOC electrohydraulic or laser lithotripsy (odds ratio, 1.02; 95%
      confidence interval, 1.01-1.03; P < .001). CONCLUSIONS: In a multicenter,
      international, retrospective analysis, we found D-SOC with electrohydraulic or
      laser lithotripsy to be effective and safe in more than 95% of patients with
      difficult biliary stones. Fewer than 5% of patients require additional treatment
      with surgery and/or extracorporeal shockwave lithotripsy to clear the duct.

PMID- 29074449
TI  - Intermittent but not sustained moderate hypoxia elicits long-term facilitation of
      hypoglossal motor output.
AB  - Phrenic long-term facilitation (pLTF) is a form of serotonin-dependent
      respiratory motor plasticity induced by moderate acute intermittent hypoxia
      (AIH), but not by moderate acute sustained hypoxia (ASH) of similar cumulative
      duration. Thus, moderate AIH-induced pLTF is sensitive to the pattern of hypoxia.
      On the other hand, pLTF induced by severe AIH protocols is neither pattern
      sensitive nor serotonin dependent (it converts to an adenosine-dependent
      mechanism). Although moderate AIH also induces hypoglossal LTF (hLTF), no data
      are available concerning its sensitivity/insensitivity to the pattern of hypoxia.
      Since hLTF following moderate hypoxia is serotonin-dependent, we hypothesized
      that hLTF is pattern-sensitive, similar to serotonin-dependent pLTF. Integrated
      hypoglossal nerve activity was recorded in urethane-anesthetized, vagotomized,
      paralyzed, and ventilated rats exposed to isocapnic AIH (3, 5min episodes of 11%
      O2) or ASH (a single 25min episode of 11% O2). Similar to previous studies of
      pLTF, hypoglossal motor output was elevated for more than 1h following AIH (50+/
      20%, p<0.01), but not ASH (-6+/-9%, p>0.05). Frequency LTF was not observed
      following either hypoxic exposure. Thus, in agreement with our hypothesis,
      hypoglossal LTF following moderate AIH is pattern-sensitive, similar to phrenic
      LTF.

PMID- 29074450
TI  - Cost-Effectiveness of Access Expansion to Treatment of Hepatitis C Virus
      Infection Through Primary Care Providers.
AB  - BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection is a major burden on
      individuals and health care systems. The Extension for Community Healthcare
      Outcomes (Project ECHO) enables primary care providers to deliver best-practice
      care for complex conditions to underserved populations. The US Congress passed
      the ECHO Act in late 2016, requiring the Department of Health and Human Services
      to investigate the model. We performed a cost-effectiveness analysis to assess
      diagnosis and treatment of HCV infection in a primary care patient panel with and
      without the implementation of Project ECHO. METHODS: We used Markov models to
      simulate disease progression, quality of life, and life expectancy among
      individuals with HCV infection and for the general population. Data from the
      University of New Mexico's ECHO operation for HCV show an increase in treatment
      rates. Corresponding increases in survival, quality-adjusted life years (QALYs),
      costs, and resulting budget impact between ECHO and non-ECHO patients with HCV
      were then compared. RESULTS: Project ECHO increased costs and QALYs. The
      incremental cost-effectiveness ratio of ECHO was $10,351 per QALY compared with
      the status quo; >99.9% of iterations fell below the willingness-to-pay threshold
      of $100,000 per QALY. We were unable to confirm whether the increase in rates of
      treatment associated with Project ECHO were due to increased or more targeted
      screening, higher adherence, or access to treatment. Our sensitivity analyses
      show that the results are largely independent of the cause. Budget impact
      analysis shows payers would have to invest an additional $339.54 million over a 5
      year period to increase treatment by 4446 patients, per 1 million covered lives.
      CONCLUSION: Using a simulated primary care patient panel, we showed that Project
      ECHO is a cost-effective way to find and treat patients with HCV infection at
      scale using existing primary care providers. This approach could substantially
      reduce the burden of chronic HCV infection in the United States, but high
      budgetary costs suggest that incremental rollout of ECHO may be best.

PMID- 29074451
TI  - Mitochondrial Dysfunction, Through Impaired Autophagy, Leads to Endoplasmic
      Reticulum Stress, Deregulated Lipid Metabolism, and Pancreatitis in Animal
      Models.
AB  - BACKGROUND & AIMS: Little is known about the signaling pathways that initiate and
      promote acute pancreatitis (AP). The pathogenesis of AP has been associated with
      abnormal increases in cytosolic Ca2+, mitochondrial dysfunction, impaired
      autophagy, and endoplasmic reticulum (ER) stress. We analyzed the mechanisms of
      these dysfunctions and their relationships, and how these contribute to
      development of AP in mice and rats. METHODS: Pancreatitis was induced in C57BL/6J
      mice (control) and mice deficient in peptidylprolyl isomerase D (cyclophilin D,
      encoded by Ppid) by administration of L-arginine (also in rats), caerulein, bile
      acid, or an AP-inducing diet. Parameters of pancreatitis, mitochondrial function,
      autophagy, ER stress, and lipid metabolism were measured in pancreatic tissue,
      acinar cells, and isolated mitochondria. Some mice with AP were given trehalose
      to enhance autophagic efficiency. Human pancreatitis tissues were analyzed by
      immunofluorescence. RESULTS: Mitochondrial dysfunction in pancreas of mice with
      AP was induced by either mitochondrial Ca2+ overload or through a Ca2+ overload
      independent pathway that involved reduced activity of ATP synthase (80%
      inhibition in pancreatic mitochondria isolated from rats or mice given L
      arginine). Both pathways were mediated by cyclophilin D and led to mitochondrial
      depolarization and fragmentation. Mitochondrial dysfunction caused pancreatic ER
      stress, impaired autophagy, and deregulation of lipid metabolism. These
      pathologic responses were abrogated in cyclophilin D-knockout mice.
      Administration of trehalose largely prevented trypsinogen activation, necrosis,
      and other parameters of pancreatic injury in mice with L-arginine AP. Tissues
      from patients with pancreatitis had markers of mitochondrial damage and impaired
      autophagy, compared with normal pancreas. CONCLUSIONS: In different animal
      models, we find a central role for mitochondrial dysfunction, and for impaired
      autophagy as its principal downstream effector, in development of AP. In
      particular, the pathway involving enhanced interaction of cyclophilin D with ATP
      synthase mediates L-arginine-induced pancreatitis, a model of severe AP the
      pathogenesis of which has remained unknown. Strategies to restore mitochondrial
      and/or autophagic function might be developed for treatment of AP.

PMID- 29074452
TI  - Progression of Pancreatic Branch Duct Intraductal Papillary Mucinous Neoplasm
      Associates With Cyst Size.
AB  - BACKGROUNDS & AIMS: Most guidelines for management of patients with intraductal
      papillary mucinous neoplasms (IPMN) vary in proposed surveillance intervals and
      durations-these are usually determined based on expert opinions rather than
      substantial evidence. The progression of and optimal surveillance intervals for
      branch-duct IPMNs (BD-IPMN) has not been widely studied. We evaluated the
      progression of BD-IPMN under surveillance at a single center, and determined
      optimal follow-up intervals and duration. METHODS: We performed a retrospective
      analysis of 1369 patients with BD-IPMN seen at Seoul National University Hospital
      in Korea from January 2001 through December 2016. We included only patients whose
      imaging studies showed classical features of BD-IPMN, and collected data from
      each patient over time periods of at least 3 years. We reviewed radiologic and
      pathologic findings, and performed linear and binary logistic regressions to
      estimate cyst growth. RESULTS: The median annual growth rate of the cyst was 0.8
      mm over a median follow-up time of 61 months. During surveillance, 46 patients
      (3.4%) underwent surgery because of disease progression after a median follow-up
      time (in this group) of 62 months. Worrisome features were observed in 209
      patients (15.3%) during surveillance, including cyst size of 3 cm or more (n =
      109, 8.0%), cyst wall thickening (n = 51, 3.7%), main pancreatic duct dilatation
      (n = 77, 5.6%), and mural nodule (n = 43, 3.1%). Along with annual rate of cyst
      growth, incidences of main pancreatic duct dilatation and mural nodules
      associated with the sizes of cysts at detection (P < .001). CONCLUSIONS: In a
      retrospective analysis of patients with BD-IPMN followed for more than 5 years,
      we found most cysts to be indolent, but some rapidly grew and progressed.
      Surveillance protocols should therefore be individualized based on initial cyst
      size and rate of growth.

PMID- 29074453
TI  - Exome-Wide Association Study of Pancreatic Cancer Risk.
AB  - We conducted a case-control exome-wide association study to discover germline
      variants in coding regions that affect risk for pancreatic cancer, combining data
      from 5 studies. We analyzed exome and genome sequencing data from 437 patients
      with pancreatic cancer (cases) and 1922 individuals not known to have cancer
      (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare
      inactivating variants (17/437 cases vs 3/1922 controls) (P = 3.27x10-6; exome
      wide statistical significance threshold P < 2.5x10-6). Cases had more rare
      inactivating variants in DNA repair genes than controls, even after excluding 13
      genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35; P =
      .045). At the suggestive threshold (P < .001), 6 genes were enriched for rare
      damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had
      associations with pancreatic cancer risk, based on the sequence-kernel
      association test. We confirmed variants in BRCA2 as the most common high
      penetrant genetic factor associated with pancreatic cancer and we also identified
      candidate pancreatic cancer genes. Large collaborations and novel approaches are
      needed to overcome the genetic heterogeneity of pancreatic cancer predisposition.

PMID- 29074454
TI  - MicroRNA.
AB  - MicroRNAs (miRNAs) are small endogenous RNAs that regulate gene-expression
      posttranscriptionally. MiRNA research in allergy is expanding because miRNAs are
      crucial regulators of gene expression and promising candidates for biomarker
      development. MiRNA mimics and miRNA inhibitors currently in preclinical
      development have shown promise as novel therapeutic agents. Multiple
      technological platforms have been developed for miRNA isolation, miRNA
      quantitation, miRNA profiling, miRNA target detection, and modulating miRNA
      levels in vitro and in vivo. Here we will review the major technological
      platforms with consideration given for the advantages and disadvantages of each
      platform.

PMID- 29074455
TI  - Evanescence wave-based technology for the rapid and sensitive quantification of
      biological analytes.

PMID- 29074456
TI  - Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic
      rhinitis.
AB  - BACKGROUND: Allergic rhinitis (AR) is characterized by mucosal inflammation,
      driven by activated immune cells. Mast cells and TH2 cells might decrease
      epithelial barrier integrity in AR, maintaining a leaky epithelial barrier.
      OBJECTIVE: We sought to investigate the role of histamine and TH2 cells in
      driving epithelial barrier dysfunction in AR. METHODS: Air-liquid interface
      cultures of primary nasal epithelial cells were used to measure transepithelial
      electrical resistance, paracellular flux of fluorescein isothiocyanate-dextran 4
      kDa, and mRNA expression of tight junctions. Nasal secretions were collected from
      healthy control subjects, AR patients, and idiopathic rhinitis patients and were
      tested in vitro. In addition, the effect of activated TH1 and TH2 cells, mast
      cells, and neurons was tested in vitro. The effect of IL-4, IL-13, IFN-gamma, and
      TNF-alpha on mucosal permeability was tested in vivo. RESULTS: Histamine as well
      as nasal secretions of AR but not idiopathic rhinitis patients rapidly decreased
      epithelial barrier integrity in vitro. Pretreatment with histamine receptor-1
      antagonist, azelastine prevented the early effect of nasal secretions of AR
      patients on epithelial integrity. Supernatant of activated TH1 and TH2 cells
      impaired epithelial integrity, while treatment with anti-TNF-alpha or anti-IL
      4Ralpha monoclonal antibodies restored the TH1- and TH2-induced epithelial
      barrier dysfunction, respectively. IL-4, IFN-gamma, and TNF-alpha enhanced
      mucosal permeability in mice. Antagonizing IL-4 prevented mucosal barrier
      disruption and tight junction downregulation in a mouse model of house dust mite
      allergic airway inflammation. CONCLUSIONS: Our data indicate a key role for
      allergic inflammatory mediators in modulating nasal epithelial barrier integrity
      in the pathophysiology in AR.

PMID- 29074457
TI  - Step-up empiric elimination diet for pediatric and adult eosinophilic
      esophagitis: The 2-4-6 study.
AB  - BACKGROUND: Numerous dietary restrictions and endoscopies limit the
      implementation of empiric elimination diets in patients with eosinophilic
      esophagitis (EoE). Milk and wheat/gluten are the most common food triggers.
      OBJECTIVE: We sought to assess the effectiveness of a step-up dietary strategy
      for EoE. METHODS: We performed a prospective study conducted in 14 centers.
      Patients underwent a 6-week 2-food-group elimination diet (TFGED; milk and gluten
      containing cereals). Remission was defined by symptom improvement and less than
      15 eosinophils/high-power field. Nonresponders were gradually offered a 4-food
      group elimination diet (FFGED; TFGED plus egg and legumes) and a 6-food-group
      elimination diet (SFGED; FFGED plus nuts and fish/seafood). In responders
      eliminated food groups were reintroduced individually, followed by endoscopy.
      RESULTS: One hundred thirty patients (25 pediatric patients) were enrolled, with
      97 completing all phases of the study. A TFGED achieved EoE remission in 56 (43%)
      patients, with no differences between ages. Food triggers in TFGED responders
      were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only
      by milk was present in 18% and 33% of adults and children, respectively.
      Remission rates with FFGEDs and SFGEDs were 60% and 79%, with increasing food
      triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED
      responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up
      strategy reduced endoscopic procedures and diagnostic process time by 20%.
      CONCLUSIONS: A TFGED diet achieves EoE remission in 43% of children and adults. A
      step-up approach results in early identification of a majority of responders to
      an empiric diet with few food triggers, avoiding unnecessary dietary
      restrictions, saving endoscopies, and shortening the diagnostic process.

PMID- 29074458
TI  - IL-10, TGF-beta, and glucocorticoid prevent the production of type 2 cytokines in
      human group 2 innate lymphoid cells.

PMID- 29074459
TI  - A novel recycling mechanism of native IgE-antigen complexes in human B cells
      facilitates transfer of antigen to dendritic cells for antigen presentation.
AB  - BACKGROUND: IgE-immune complexes (IgE-ICs) have been shown to enhance antibody
      and T-cell responses in mice by targeting CD23 (FcepsilonRII), the low-affinity
      receptor for IgE on B cells. In humans, the mechanism by which CD23-expressing
      cells take up IgE-ICs and process them is not well understood. OBJECTIVE: To
      investigate this question, we compared the fate of IgE-ICs in human B cells and
      in CD23-expressing monocyte-derived dendritic cells (moDCs) that represent
      classical antigen-presenting cells and we aimed at studying IgE-dependent antigen
      presentation in both cell types. METHODS: B cells and monocytes were isolated
      from peripheral blood, and monocytes were differentiated into moDCs. Both cell
      types were stimulated with IgE-ICs consisting of 4-hydroxy-3-iodo-5
      nitrophenylacetyl (NIP)-specific IgE JW8 and NIP-BSA to assess binding, uptake,
      and degradation dynamics. To assess CD23-dependent T-cell proliferation, B cells
      and moDCs were pulsed with IgE-NIP-tetanus toxoid complexes and cocultured with
      autologous T cells. RESULTS: IgE-IC binding was CD23-dependent in B cells, and
      moDCs and CD23 aggregation, as well as IgE-IC internalization, occurred in both
      cell types. Although IgE-ICs were degraded in moDCs, B cells did not degrade the
      complexes but recycled them in native form to the cell surface, enabling IgE-IC
      uptake by moDCs in cocultures. The resulting proliferation of specific T cells
      was dependent on cell-cell contact between B cells and moDCs, which was explained
      by increased upregulation of costimulatory molecules CD86 and MHC class II on
      moDCs induced by B cells. CONCLUSIONS: Our findings argue for a novel model in
      which human B cells promote specific T-cell proliferation on IgE-IC encounter. On
      one hand, B cells act as carriers transferring antigen to more efficient antigen
      presenting cells such as DCs. On the other hand, B cells can directly promote DC
      maturation and thereby enhance T-cell stimulation.

PMID- 29074460
TI  - Molecular and morphological data reveal non-monophyly and speciation in imperiled
      freshwater mussels (Anodontoides and Strophitus).
AB  - Accurate taxonomic placement is vital to conservation efforts considering many
      intrinsic biological characteristics of understudied species are inferred from
      closely related taxa. The rayed creekshell, Anodontoides radiatus (Conrad, 1834),
      exists in the Gulf of Mexico drainages from western Florida to Louisiana and has
      been petitioned for listing under the Endangered Species Act. We set out to
      resolve the evolutionary history of A. radiatus, primarily generic placement and
      species boundaries, using phylogenetic, morphometric, and geographic information.
      Our molecular matrix contained 3 loci: cytochrome c oxidase subunit I, NADH
      dehydrogenase subunit I, and the nuclear-encoded ribosomal internal transcribed
      spacer I. We employed maximum likelihood and Bayesian inference to estimate a
      phylogeny and test the monophyly of Anodontoides and Strophitus. We implemented
      two coalescent-based species delimitation models to test seven species models and
      evaluate species boundaries within A. radiatus. Concomitant to molecular data, we
      also employed linear morphometrics and geographic information to further evaluate
      species boundaries. Molecular and morphological evidence supports the inclusion
      of A. radiatus in the genus Strophitus, and we resurrect the binomial Strophitus
      radiatus to reflect their shared common ancestry. We also found strong support
      for polyphyly in Strophitus and advocate the resurrection of the genus
      Pseudodontoideus to represent 'Strophitus' connasaugaensis and 'Strophitus'
      subvexus. Strophitus radiatus exists in six well-supported clades that were
      distinguished as evolutionary independent lineages using Bayesian inference,
      maximum likelihood, and coalescent-based species delimitation models. Our
      integrative approach found evidence for as many as 4 evolutionary divergent
      clades within S. radiatus. Therefore, we formally describe two new species from
      the S. radiatus species complex (Strophitus williamsi and Strophitus
      pascagoulaensis) and recognize the potential for a third putative species
      (Strophitus sp. cf. pascagoulaensis). Our findings aid stakeholders in
      establishing conservation and management strategies for the members of
      Anodontoides, Strophitus, and Pseudodontoideus.

PMID- 29074462
TI  - Correlation between telomerase and mTOR pathway in cancer stem cells.
AB  - Cancer stem cells (CSCs), which are defined as a subset of tumor cells, are able
      to self-renew, proliferate, differentiate similar to normal stem cells.
      Therefore, targeting CSCs has been considered as a new approach in cancer
      therapy. The mammalian target of rapamycin (mTOR) is a receptor tyrosine kinase
      which plays an important role in regulating cell proliferation, differentiation,
      cell growth, self-renewal in CSCs. On the other hand, hTERT overactivation
      provides replicative feature and immortality to CSCs, so the stemness and
      replicative properties of CSCs depend on telomerase activity. Therefore
      hTERT/telomerase activity may become a universal biomarker for anticancer therapy
      and it is an attractive therapeutic target for CSCs. It is known that mTOR
      regulates telomerase activity at the translational and post-translational level.
      Researchers show that mTOR inhibitor rapamycin reduces telomerase activity
      without changing hTERT mRNA activity. Correlation between mTOR and hTERT is
      important for survival and immortality of cancer cells. In addition, the
      PI3K/AKT/mTOR signaling pathway and hTERT up-regulation are related with cancer
      stemness features and drug resistance. mTOR inhibitor and TERT inhibitor
      combination may construct a novel strategy in cancer stem cells and it can make a
      double effect on telomerase enzyme. Consequently, inhibition of PI3K/AKT/mTOR
      signaling pathway components and hTERT activation may prohibit CSC self-renewal
      and surpass CSC-mediated resistance in order to develop new cancer therapeutics.

PMID- 29074461
TI  - Comprehensive phylogeny of acariform mites (Acariformes) provides insights on the
      origin of the four-legged mites (Eriophyoidea), a long branch.
AB  - Eriophyoid, or four-legged mites, represent a large and ancient radiation of
      exclusively phytophagous organisms known from the Triassic (230 Mya).
      Hypothesizing phylogenetic relatedness of Eriophyoidea among mites is a major
      challenge due to the absence of unambiguous morphological synapomorphies,
      resulting in ten published hypotheses placing eriophyoids in various places in
      the acariform tree of life. Here we test the evolutionary relationships of
      eriophyoids using six genes and a representative taxonomic sampling of acariform
      mites. The total evidence analysis places eriophyoids as the sister group of the
      deep soil-dwelling, vermiform family Nematalycidae (Endeostigmata). This
      arrangement was supported by the rDNA and CO1 partitions. In contrast, the
      nuclear protein partition (genes EF1-alpha, SRP54, HSP70) suggests that
      Eriophyoidea is sister to a lineage including Tydeidae, Ereynetidae, and
      Eupodidae (Eupodina: Trombidiformes). On both of these alternative topologies,
      eriophyoids appear as a long branch, probably involving the loss of basal
      diversity in early evolution. We analyze this result by using phylogenetically
      explicit hypothesis testing, investigating the phylogenetic signal from
      individual genes and rDNA stem and loop regions, and removing long branches and
      rogue taxa. Regardless of the two alternative placements, (i) the cheliceral
      morphology of eriophyoids, one of the traits deemed phylogenetically important,
      was likely derived directly from the plesiomorphic acariform chelicerae rather
      than from the modified chelicerae of some trombidiform lineages with a reduced
      fixed digit; and (ii) two potential synapomorphies of Eriophyoidea+Raphignathina
      (Trombidiformes) related to the reduction of genital papillae and to the terminal
      position of PS segment can be dismissed as result of convergent evolution. Our
      analyses substantially narrow the remaining available hypotheses on eriophyoid
      relationships and provide insights on the early evolution of acariform mites.

PMID- 29074463
TI  - Disruption of AT-hook 1 domain in MeCP2 protein caused behavioral abnormality in
      mice.
AB  - MECP2 is the causative gene for autism spectrum disorders, including Rett
      syndrome, a regressive neurodevelopmental rare disease mainly occurring in girls.
      Except for the distinct methyl-CpG binding domain and the transcriptional
      repression domain in MeCP2, three AT-hook-like domains have recently been
      identified. Several mutations in AT-hook 1 domain have been reported in autism
      cases or Rett database. However, the role of AT-hook 1 domain is still unclear.
      In this study, we generated a mouse line carrying deletion of eight conserved
      amino acids in AT-hook 1 domain by clustered regularly interspaced short
      palindromic repeats (CRISPR)/Cas9 technology. Mecp2DeltaAT-hook1/y mutant male
      mice exhibited low locomotor activity, motor incoordination and cognitive
      deficit. In addition, these mutant mice exhibited increased anxiety. Moreover,
      pain insensitivity was noted in the mutant males. However, the social
      interactions were unaffected in AT-hook 1 mutant mice. Thinner CA1 region of the
      hippocampus was observed in the mutant mice. On the molecular basis, Western blot
      analysis showed increased expression of mutant MeCP2 protein in the cortex.
      Additionally, several genes expressed specifically in inhibitory neurons were
      markedly changed in the cerebrum. Taken together, these data demonstrate that
      disruption of AT-hook 1 domain in MeCP2 caused behavioral abnormality in mice,
      which suggests that AT-hook 1 is a critical region for the function of MeCP2
      protein.

PMID- 29074464
TI  - Regulatory crosstalk between KLF5, miR-29a and Fbw7/CDC4 cooperatively promotes
      atherosclerotic development.
AB  - Atherogenesis is a chronic inflammatory process that involves complex
      interactions between endothelial dysfunction, lipid deposition and vascular
      smooth-muscle cell (VSMC) proliferation. However, the molecular mechanism is
      still unclear. We found that a pro-atherosclerotic factor (oxLDL) induced the
      expression of Kruppel-like factor 5 (KLF5), which in turn increased miR-29a
      expression levels. The increased miR-29a was retained within HASMCs and down
      regulated Fbw7/CDC4 expression by targeting the 3'UTR of Fbw7/CDC4, subsequently
      increasing KLF5 stability by reducing the Fbw7/CDC4-dependent ubiquitination of
      KLF5, forming a positive feedback loop to enhance VSMC proliferation and promote
      atherogenesis. These results indicate a potentially important role for the oxLDL
      activated feedback mechanism in VSMC proliferation and atherogenesis. Suppression
      of miR-29a may be an effective way to attenuate atherosclerosis. In conclusion,
      our data are the first to reveal that the regulatory crosstalk between KLF5, miR
      29a, and Fbw7/CDC4 cooperatively promotes atherosclerotic development.

PMID- 29074465
TI  - Comparison of three-dimensional helical axes of the cervical spine between in
      vitro and in vivo testing.
AB  - BACKGROUND CONTEXT: The range of motion is a well-accepted parameter for the
      assessment and evaluation of cervical motion. However, more qualitative data of
      the kinematics of the cervical spine are needed for the development and success
      of cervical disc arthroplasty. PURPOSE: The aim of this study was to provide
      basic information about helical axes of human cervical spine under in vitro
      conditions. Furthermore, it should clarify whether the three-dimensional helical
      axes of cervical motion gained from in vitro experiments are in agreement with
      those gained from in vivo experiments, and therefore to prove its reliability.
      STUDY DESIGN/SETTING: An in vitro test with pure moments and mono-segmental
      specimens was designed to investigate and compare the helical axes of the
      cervical spine. METHODS: Six human cadaveric specimens (three male and three
      female) with an average age of 47.5 years (range: 34-58 years) were carefully
      selected. Each specimen was divided into three motion segments: C2-C3, C4-C5, and
      C6-C7. We performed 3.5 full cycles of rotation about all axes, flexion
      extension, lateral bending, and axial rotation, by applying pure moments of 1.5
      Nm without any preload. Following the in vitro tests, the three-dimensional
      helical axes were calculated and projected into the x-ray images. RESULTS:
      Rotation analysis of all three directions revealed similar results for all six
      specimens. All calculated helical axes were similar to the published in vivo
      data. Furthermore, the instantaneous centers of rotation were in agreement with
      in vivo data. CONCLUSIONS: The data gained from this study verify cervical
      kinematics during in vitro testing using pure moments. It can be assumed that
      other soft tissue such as muscles are not necessarily needed to simulate cervical
      kinematics in vitro.

PMID- 29074466
TI  - Neuroprotective assessment of prolonged local hypothermia post contusive spinal
      cord injury in rodent model.
AB  - BACKGROUND CONTEXT: Although general hypothermia is recognized as a clinically
      applicable neuroprotective intervention, acute moderate local hypothermia post
      contusive spinal cord injury (SCI) is being considered a more effective approach.
      Previously, we have investigated the feasibility and safety of inducing prolonged
      local hypothermia in the central nervous system of a rodent model. PURPOSE: Here,
      we aimed to verify the efficacy and neuroprotective effects of 5 and 8 hours of
      local moderate hypothermia (30+/-0.5 degrees C) induced 2 hours after moderate
      thoracic contusive SCI in rats. STUDY DESIGN: Rats were induced with moderate SCI
      (12.5 mm) at its T8 section. Local hypothermia (30+/-0.5 degrees C) was induced 2
      hours after injury induction with an M-shaped copper tube with flow of cold water
      (12 degrees C), from the T6 to the T10 region. Experiment groups were divided
      into 5-hour and 8-hour hypothermia treatment groups, respectively, whereas the
      normothermia control group underwent no hypothermia treatment. METHODS: The
      neuroprotective effects were assessed through objective weekly somatosensory
      evoked potential (SSEP) and motor behavior (basso, beattie and bresnahan Basso,
      Beattie and Bresnahan (BBB) scoring) monitoring. Histology on spinal cord was
      performed until at the end of day 56. All authors declared no conflict of
      interest. This work was supported by the Singapore Institute for Neurotechnology
      Seed Fund (R-175-000-121-733), National University of Singapore, Ministry of
      Education, Tier 1 (R-172-000-414-112.). RESULTS: Our results show significant
      SSEP amplitudes recovery in local hypothermia groups starting from day 14 post
      injury onward for the 8-hour treatment group, which persisted up to days 28 and
      42, whereas the 5-hour group showed significant improvement only at day 42. The
      functional improvement plateaued after day 42 as compared with control group of
      SCI with normothermia. This was supported by both 5-hour and 8-hour improvement
      in locomotion as measured by BBB scores. Local hypothermia also observed
      insignificant changes in its SSEP latency, as compared with the control. In
      addition, 5- and 8-hour hypothermia rats' spinal cord showed higher percentage of
      parenchyma preservation. CONCLUSIONS: Early local moderate hypothermia can be
      induced for extended periods of time post SCI in the rodent model. Such
      intervention improves functional electrophysiological outcome and motor behavior
      recovery for a long time, lasting until 8 weeks.

PMID- 29074467
TI  - Vertebral body spread in thoracolumbar burst fractures can predict posterior
      construct failure.
AB  - BACKGROUND CONTEXT: The load sharing classification (LSC) laid foundations for a
      scoring system able to indicate which thoracolumbar fractures, after short
      segment posterior-only fixations, would need longer instrumentations or
      additional anterior supports. PURPOSE: We analyzed surgically treated
      thoracolumbar fractures, quantifying the vertebral body's fragment displacement
      with the aim of identifying a new parameter that could predict the posterior-only
      construct failure. STUDY DESIGN: This is a retrospective cohort study from a
      single institution. PATIENT SAMPLE: One hundred twenty-one consecutive patients
      were surgically treated for thoracolumbar burst fractures. OUTCOME MEASURES:
      Grade of kyphosis correction (GKC) expressed radiological outcome; Oswestry
      Disability Index and visual analog scale were considered. METHODS: One hundred
      twenty-one consecutive patients who underwent posterior fixation for unstable
      thoracolumbar burst fractures were retrospectively evaluated clinically and
      radiologically. Supplementary anterior fixations were performed in 34 cases with
      posterior instrumentation failure, determined on clinic-radiological evidence or
      symptomatic loss of kyphosis correction. Segmental kyphosis angle and GKC were
      calculated according to the Cobb method. The displacement of fracture fragments
      was obtained from the mean of the adjacent end plate areas subtracted from the
      area enclosed by the maximum contour of vertebral fragmentation. The "spread" was
      derived from the ratio between this subtraction and the mean of the adjacent end
      plate areas. Analysis of variance, Mann-Whitney, and receiver operating
      characteristic were performed for statistical analysis. The authors report no
      conflict of interest concerning the materials or methods used in the present
      study or the findings specified in this paper. No funds or grants have been
      received for the present study. RESULTS: The spread revealed to be a helpful
      quantitative measurement of vertebral body fragment displacement, easily
      reproducible with the current computed tomography (CT) imaging technologies.
      There were no failures of posterior fixations with preoperative spreads <42% and
      losses of correction (LOC)<10 degrees , whereas spreads >62.7% required
      supplementary anterior supports whenever LOC>10 degrees  were recorded. Most of
      the patients in a "gray zone," with spreads between 42% and 62.7%, needed
      additional anterior supports because of clinical-radiological evidence of
      impending mechanical failures, which developed independently from the GKC.
      Preoperative kyphosis (p<.001), load sharing score (p=.002), and spread (p<.001)
      significantly affected the final surgical treatment (posterior or
      circumferential). CONCLUSIONS: Twenty-two years after the LSC, both improvements
      in spinal stabilization systems and software imaging innovations have modified
      surgical concepts and approach on spinal trauma care. Spread was found to be an
      additional tool that could help in predicting the posterior construct failure,
      providing an objective preoperative indicator, easily reproducible with the
      modern viewers for CT images.

PMID- 29074468
TI  - Functional diversity of macrophages in vascular biology and disease.
AB  - Atherosclerosis is a multifactorial chronic inflammatory disease and is largely
      responsible for cardiovascular disease, the most common cause of global
      mortality. The hallmark of atherogenesis is immune activation following lipid
      accumulation in the arterial wall. In particular, macrophages play a non
      redundant role in both the progression and regression of inflammation in the
      atherosclerotic lesion. Macrophages are remarkably heterogeneous phagocytes that
      perform versatile functions in health and disease. Their functional diversity in
      vascular biology is only partially mapped. Targeting macrophages is often
      highlighted as a therapeutic approach for cancer, metabolic and inflammatory
      diseases. Future strategies for therapeutic intervention in atherosclerosis may
      benefit from attempts to reduce local proliferation of pro-inflammatory
      macrophage subsets or enhance resolution of inflammation. Thus, characterisation
      of macrophage subsets during atherosclerosis would empower clinical
      interventions. Therefore, it would be of fundamental importance to understand how
      pathological factors modulate macrophage activity in order to exploit their use
      in the treatment of atherosclerosis and other diseases.

PMID- 29074469
TI  - Adverse Reactions Associated With Cannabis Consumption as Evident From Search
      Engine Queries.
AB  - BACKGROUND: Cannabis is one of the most widely used psychoactive substances
      worldwide, but adverse drug reactions (ADRs) associated with its use are
      difficult to study because of its prohibited status in many countries. OBJECTIVE:
      Internet search engine queries have been used to investigate ADRs in
      pharmaceutical drugs. In this proof-of-concept study, we tested whether these
      queries can be used to detect the adverse reactions of cannabis use. METHODS: We
      analyzed anonymized queries from US-based users of Bing, a widely used search
      engine, made over a period of 6 months and compared the results with the
      prevalence of cannabis use as reported in the US National Survey on Drug Use in
      the Household (NSDUH) and with ADRs reported in the Food and Drug
      Administration's Adverse Drug Reporting System. Predicted prevalence of cannabis
      use was estimated from the fraction of people making queries about cannabis,
      marijuana, and 121 additional synonyms. Predicted ADRs were estimated from
      queries containing layperson descriptions to 195 ICD-10 symptoms list. RESULTS:
      Our results indicated that the predicted prevalence of cannabis use at the US
      census regional level reaches an R2 of .71 NSDUH data. Queries for ADRs made by
      people who also searched for cannabis reveal many of the known adverse effects of
      cannabis (eg, cough and psychotic symptoms), as well as plausible unknown
      reactions (eg, pyrexia). CONCLUSIONS: These results indicate that search engine
      queries can serve as an important tool for the study of adverse reactions of
      illicit drugs, which are difficult to study in other settings.

PMID- 29074470
TI  - Posttraumatic Stress Disorder and Mobile Health: App Investigation and Scoping
      Literature Review.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent mental health
      issue among veterans. Access to PTSD treatment is influenced by geographic (ie,
      travel distance to facilities), temporal (ie, time delay between services),
      financial (ie, eligibility and cost of services), and cultural (ie, social
      stigma) barriers. OBJECTIVE: The emergence of mobile health (mHealth) apps has
      the potential to bridge many of these access gaps by providing remote resources
      and monitoring that can offer discrete assistance to trauma survivors with PTSD
      and enhance patient-clinician relationships. In this study, we investigate the
      current mHealth capabilities relevant to PTSD. METHODS: This study consists of
      two parts: (1) a review of publicly available PTSD apps designed to determine the
      availability of PTSD apps, which includes more detailed information about three
      dominant apps and (2) a scoping literature review performed using a systematic
      method to determine app usage and efforts toward validation of such mHealth apps.
      App usage relates to how the end users (eg, clinicians and patients) are
      interacting with the app, whereas validation is testing performed to ensure the
      app's purpose and specifications are met. RESULTS: The results suggest that
      though numerous apps have been developed to aid in the diagnosis and treatment of
      PTSD symptoms, few apps were designed to be integrated with clinical PTSD
      treatment, and minimal efforts have been made toward enhancing the usability and
      validation of PTSD apps. CONCLUSIONS: These findings expose the need for studies
      relating to the human factors evaluation of such tools, with the ultimate goal of
      increasing access to treatment and widening the app adoption rate for patients
      with PTSD.

PMID- 29074471
TI  - Reliability and Validity of the Telephone-Based eHealth Literacy Scale Among
      Older Adults: Cross-Sectional Survey.
AB  - BACKGROUND: Only a handful of studies have examined reliability and validity
      evidence of scores produced by the 8-item eHealth literacy Scale (eHEALS) among
      older adults. Older adults are generally more comfortable responding to survey
      items when asked by a real person rather than by completing self-administered
      paper-and-pencil or online questionnaires. However, no studies have explored the
      psychometrics of this scale when administered to older adults over the telephone.
      OBJECTIVE: The objective of our study was to examine the reliability and internal
      structure of eHEALS data collected from older adults aged 50 years or older
      responding to items over the telephone. METHODS: Respondents (N=283) completed
      eHEALS as part of a cross-sectional landline telephone survey. Exploratory
      structural equation modeling (E-SEM) analyses examined model fit of eHEALS scores
      with 1-, 2-, and 3-factor structures. Subsequent analyses based on the partial
      credit model explored the internal structure of eHEALS data. RESULTS: Compared
      with 1- and 2-factor models, the 3-factor eHEALS structure showed the best global
      E-SEM model fit indices (root mean square error of approximation=.07; comparative
      fit index=1.0; Tucker-Lewis index=1.0). Nonetheless, the 3 factors were highly
      correlated (r range .36 to .65). Item analyses revealed that eHEALS items 2
      through 5 were overfit to a minor degree (mean square infit/outfit values <1.0; t
      statistics less than -2.0), but the internal structure of Likert scale response
      options functioned as expected. Overfitting eHEALS items (2-5) displayed a
      similar degree of information for respondents at similar points on the latent
      continuum. Test information curves suggested that eHEALS may capture more
      information about older adults at the higher end of the latent continuum (ie,
      those with high eHealth literacy) than at the lower end of the continuum (ie,
      those with low eHealth literacy). Item reliability (value=.92) and item
      separation (value=11.31) estimates indicated that eHEALS responses were reliable
      and stable. CONCLUSIONS: Results support administering eHEALS over the telephone
      when surveying older adults regarding their use of the Internet for health
      information. eHEALS scores best captured 3 factors (or subscales) to measure
      eHealth literacy in older adults; however, statistically significant correlations
      between these 3 factors suggest an overarching unidimensional structure with 3
      underlying dimensions. As older adults continue to use the Internet more
      frequently to find and evaluate health information, it will be important to
      consider modifying the original eHEALS to adequately measure societal shifts in
      online health information seeking among aging populations.

PMID- 29074472
TI  - External Validation Study of First Trimester Obstetric Prediction Models (Expect
      Study I): Research Protocol and Population Characteristics.
AB  - BACKGROUND: A number of first-trimester prediction models addressing important
      obstetric outcomes have been published. However, most models have not been
      externally validated. External validation is essential before implementing a
      prediction model in clinical practice. OBJECTIVE: The objective of this paper is
      to describe the design of a study to externally validate existing first trimester
      obstetric prediction models, based upon maternal characteristics and standard
      measurements (eg, blood pressure), for the risk of pre-eclampsia (PE),
      gestational diabetes mellitus (GDM), spontaneous preterm birth (PTB), small-for
      gestational-age (SGA) infants, and large-for-gestational-age (LGA) infants among
      Dutch pregnant women (Expect Study I). The results of a pilot study on the
      feasibility and acceptability of the recruitment process and the
      comprehensibility of the Pregnancy Questionnaire 1 are also reported. METHODS: A
      multicenter prospective cohort study was performed in The Netherlands between
      July 1, 2013 and December 31, 2015. First trimester obstetric prediction models
      were systematically selected from the literature. Predictor variables were
      measured by the Web-based Pregnancy Questionnaire 1 and pregnancy outcomes were
      established using the Postpartum Questionnaire 1 and medical records. Information
      about maternal health-related quality of life, costs, and satisfaction with Dutch
      obstetric care was collected from a subsample of women. A pilot study was carried
      out before the official start of inclusion. External validity of the models will
      be evaluated by assessing discrimination and calibration. RESULTS: Based on the
      pilot study, minor improvements were made to the recruitment process and online
      Pregnancy Questionnaire 1. The validation cohort consists of 2614 women. Data
      analysis of the external validation study is in progress. CONCLUSIONS: This study
      will offer insight into the generalizability of existing, non-invasive first
      trimester prediction models for various obstetric outcomes in a Dutch obstetric
      population. An impact study for the evaluation of the best obstetric prediction
      models in the Dutch setting with respect to their effect on clinical outcomes,
      costs, and quality of life-Expect Study II-is being planned. TRIAL REGISTRATION:
      Netherlands Trial Registry (NTR): NTR4143;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4143 (Archived by
      WebCite at http://www.webcitation.org/6t8ijtpd9).

PMID- 29074473
TI  - Is laser acupuncture an effective complementary therapy for obesity management? A
      systematic review of clinical trials.
AB  - BACKGROUND: Complementary therapies may increase the success rate of weight loss
      via a calorie-restricted diet. Acupuncture is a popular complementary therapy for
      obesity management. To our knowledge, no studies have summarised the effects of
      laser acupuncture (LA) on obesity. OBJECTIVE: To evaluate the efficacy of LA, in
      particular with respect to its impact on anthropometric features and appetite in
      obese adults, by conducting a systematic review of previous clinical trials.
      METHODS: We searched PubMed/Medline, Scopus, Web of Science, the Cochrane
      Library, Embase and Google Scholar electronic databases for papers published
      through October 2016. All clinical trials in English containing either
      anthropometric indices or appetite parameters were included. Two reviewers
      independently examined studies based on a predefined form for data extraction and
      the Jadad scale for quality assessment in order to minimise bias throughout the
      evaluation. RESULTS: After screening the papers, seven clinical trials met the
      criteria and were included in the systematic review. Positive effects of LA
      therapy were seen in body weight (n=3), body mass index (n=5), waist
      circumference (n=4), hip circumference (n=3), waist to hip ratio (n=4) and % fat
      mass (n=3). Appetite parameters were reported in one study, which showed that LA
      can reduce appetite and increase the sensation of feeling full. CONCLUSION:
      Although some studies have indicated beneficial effects for LA on obesity, the
      lack of evidence with high methodological quality made it impossible to reach a
      definitive conclusion about the efficacy of LA for obesity management. Further
      high-quality, randomised, sham-controlled clinical trials with a larger sample
      size are needed to shed light on the efficacy of LA for obesity management and
      weight maintenance.

PMID- 29074474
TI  - Musculoskeletal injury profiles in professional Women's Tennis Association
      players.
AB  - OBJECTIVE: The physical demands of professional tennis combined with high
      training/match loads can contribute to musculoskeletal injury. The objectives of
      this study were to (1) describe the type, location and severity of injuries
      sustained during a 12-month tennis season in a cohort of professional female
      tennis players on the Women's Tennis Association (WTA) tour and (2) prospectively
      investigate associations between training/match loads and injury. METHODS: 52 WTA
      players competing at the Australian Open (2015) consented to participate.
      Injuries reported to WTA medical staff were classified using tennis-specific
      guidelines. Individual match exposure data were collected for all matches played
      at international level in 2015 and expressed per 1000 hours of WTA competition
      matchplay (MP) and 1000 match exposures (MEs). Variables associated with the
      number of injuries in the season and loss of time from competition were
      identified with regression analysis. RESULTS: The injury incidence rate (IR) was
      56.6 (95% CI: 49.5 to 64.6) per 1000 hours of MP or 62.7 (95% CI: 54.8 to 71.6)
      per 1000 MEs, although the IR of injuries resulting in loss of time from
      competition was lower (12.8 per 1000 hours of MP, 92 injuries/100 players). Lower
      limb (51%) and muscle/tendon (50%) injuries were the most common site and type of
      injury. Common specific injury site subcategories were the thigh,
      shoulder/clavicle, ankle and knee in order of frequency. Various measures of
      match load were significantly associated with injury. CONCLUSION: This study
      prospectively analysed injury profiles, including severity across an entire
      season of professional tennis, and investigated the relationship between
      training/match loads and injury. These data may help medical professionals
      develop injury risk identification and prevention programmes.

PMID- 29074475
TI  - Effectiveness of school-based physical activity programmes on cardiorespiratory
      fitness in children: a meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To conduct a meta-analysis of randomised controlled trials aimed at
      testing whether school-based physical activity programmes improve
      cardiorespiratory fitness (CRF) in children. DESIGN: Systematic review with meta
      analysis. DATA SOURCES: Using keywords, we performed a computerised search in
      five databases: MEDLINE, EMBASE, CINAHL, Web of Science and SportDiscus.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies that assessed the
      effectiveness of school-based physical activity programmes on improving CRF in
      children (3-12 years old). We selected interventions that included an additional
      physical activity programme and not only a physical activity educational
      component. The reference lists of selected full-text articles and systematic
      reviews were also searched for relevant studies. Pooled effect size (Hedges' g)
      was calculated assuming a random-effects model. RESULTS: Twenty trials with 7287
      healthy children aged 3-12 years were included in the meta-analysis. School-based
      physical activity interventions with aerobic games and activities were associated
      with a significant small increase in CRF (Hedges' g=0.22; 95% CI 0.14 to 0.30;
      p<0.001). Based on subgroup analysis, the increase in CRF was significant in
      girls (Hedges' g=0.25; 95% CI 0.13 to 0.37; p<0.001), but not in boys (Hedges'
      g=0.02; 95% CI -0.10 to 0.14; p=0.731). SUMMARY: Moderate quality evidence
      supports the effectiveness of school-based physical activity interventions on
      improving CRF in children. TRIAL REGISTRATION NUMBER: Protocol PROSPERO
      registration number CRD42016050173.

PMID- 29074476
TI  - Epidemiology of imaging-detected bone stress injuries in athletes participating
      in the Rio de Janeiro 2016 Summer Olympics.
AB  - BACKGROUND: Bone stress injuries are common in high-level athletics. AIM: To
      describe the demographics, frequency and anatomical location of stress injuries
      (ie, stress reaction and stress fractures) in athletes at the Rio de Janeiro 2016
      Summer Olympic Games. METHODS: We recorded all sports injuries at the Rio de
      Janeiro 2016 Summer Olympics reported by the National Olympic Committee (NOC)
      medical teams and in the polyclinic and medical venues. Imaging was performed
      through the official IOC clinic within the Olympic Village, using digital X-ray
      cameras and 3T and 1.5T magnetic resonance (MR) scanners. Images were read
      centrally and retrospectively by musculoskeletal radiologists with expertise in
      sports injuries. RESULTS: 11 274 athletes (5089 women (45%), 6185 men (55%)) from
      207 NOCs participated in the study. 1101 injuries were reported. Imaging revealed
      9 stress fractures (36%) and 16 stress reactions (64%) in 18 female and 7 male
      athletes (median age 25 years, age range 18-32). Stress injuries were mostly in
      the lower extremities (84%), particularly tibia (44%) and metatarsals (12%), with
      two in the lumbar spine (8%). Stress injuries were most common in track and field
      athletes (44%) followed by volleyball players (16%), gymnastics (artistic) (12%)
      and other type of sports. CONCLUSIONS: Twenty-five bone stress injuries were
      reported, more commonly in women, mostly in the lower extremities and most
      commonly in track and field athletes. Our study demonstrates the importance of
      early imaging with MRI to detect stress reactions before they can progress to
      stress fractures.

PMID- 29074477
TI  - Sport, sex and age increase risk of illness at the Rio 2016 Summer Paralympic
      Games: a prospective cohort study of 51 198 athlete days.
AB  - OBJECTIVE: To describe the epidemiology of illness at the Rio 2016 Summer
      Paralympic Games. METHODS: A total of 3657 athletes from 78 countries,
      representing 83.5% of all athletes at the Games, were monitored on the web-based
      injury and illness surveillance system (WEB-IISS) over 51 198 athlete days during
      the Rio 2016 Summer Paralympic Games. Illness data were obtained daily from teams
      with their own medical support through the WEB-IISS electronic data capturing
      systems. RESULTS: The total number of illnesses was 511, with an illness
      incidence rate (IR) of 10.0 per 1000 athlete days (12.4%). The highest IRs were
      reported for wheelchair fencing (14.9), para swimming (12.6) and wheelchair
      basketball (12.5) (p<0.05). Female athletes and older athletes (35-75 years) were
      also at higher risk of illness (both p<0.01). Illnesses in the respiratory, skin
      and subcutaneous and digestive systems were the most common (IRs of 3.3, 1.8 and
      1.3, respectively). CONCLUSION: (1) The rate of illness was lower than that
      reported for the London 2012 Summer Paralympic Games; (2) the sports with the
      highest risk were wheelchair fencing, para swimming and wheelchair basketball;
      (3) female and older athletes (35-75 years) were at increased risk of illness;
      and (4) the respiratory system, skin and subcutaneous system and digestive system
      were most affected by illness. These results allow for comparison at future
      Games.

PMID- 29074479
TI  - An editor's perspective on peer review.

PMID- 29074478
TI  - Connective tissue injury in calf muscle tears and return to play: MRI
      correlation.
AB  - OBJECTIVE: The aim of our study was to assess a group of patients with calf
      muscle tears and evaluate the integrity of the connective tissue boundaries and
      interfaces. Further, we propose a novel MRI grading system based on integrity of
      the connective tissue and assess any correlation between the grading score and
      time to return to play. We have also reviewed the anatomy of the calf muscles.
      MATERIALS AND METHODS: We retrospectively evaluated 100 consecutive patients with
      clinical suspicion and MRI confirmation of calf muscle injury. We evaluated each
      calf muscle tear with MRI for the particular muscle injured, location of injury
      within the muscle and integrity of the connective tissue structure at the
      interface. The muscle tears were graded 0-3 depending on the degree of muscle and
      connective tissue injury. The time to return to play for each patient and each
      injury was found from the injury records and respective sports doctors. RESULTS:
      In 100 patients, 114 injuries were detected. Connective tissue involvement was
      observed in 63 out of 100 patients and failure (grade 3 injury) in 18. Mean time
      to return to play with grade 0 injuries was 8 days, grade 1 tears was 17 days,
      grade 2 tears was 25 days and grade 3 tears was 48 days (p<0.001). CONCLUSION:
      The integrity of the connective tissue can be used to estimate and guide the time
      to return to play in calf muscle tears.

PMID- 29074481
TI  - Improving peer review: What authors can do.

PMID- 29074480
TI  - Improving peer review: What journals can do.

PMID- 29074482
TI  - Improving peer review: What reviewers can do.

PMID- 29074483
TI  - Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics
      and renal and cardiac function in patients with cirrhosis.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal
      hypertension and possibly increases central blood volume (CBV). Moreover, renal
      function often improves; however, its effects on cardiac function are unclear.
      The aims of our study were to examine the effects of TIPS on hemodynamics and
      renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients,
      we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of
      the liver veins and right heart chambers before and 1 wk after TIPS.
      Additionally, we measured renal and cardiac markers and performed advanced
      echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased
      significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased
      (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005),
      whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures
      increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%,
      P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk
      after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase
      associated lipocalin, renin, aldosterone, and serum creatinine decreased after
      TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005,
      respectively). Echocardiography revealed subtle changes in cardiac function after
      TIPS, although these were within the normal range. TIPS increases CBV by
      increasing CO and SV, whereas HR is initially unaltered. These results indicate
      an inability to increase the heart rate in response to a hemodynamic challenge
      that only partially increases CBV after TIPS. These changes, however, are
      sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we
      have combined advanced techniques to study the integrated effects of transjugular
      intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS
      increases central blood volume (CBV) through improved cardiac inotropy. Advanced
      echocardiography demonstrated that myocardial function was unaffected by the
      dramatic increase in preload after TIPS. Finally, renal function improved due to
      the increase in CBV. Recognition of these physiological changes significantly
      contributes to our clinical understanding of TIPS.

PMID- 29074485
TI  - Animal models of chemotherapy-induced mucositis: translational relevance and
      challenges.
AB  - Chemotherapy for cancer patients induces damaging tissue reactions along the
      epithelium of the gastrointestinal tract (GIT). This chemotherapy-induced
      mucositis (CIM) is a serious side effect of cytotoxic drugs, and several animal
      models of CIM have been developed, mainly in rodents and piglets, to help
      understand the progression of CIM and how to prevent it. Animal models allow
      highly controlled experimental conditions, detailed organ (e.g., GIT) insights,
      standardized, clinically relevant treatment regimens, and discovery of new
      biomarkers. Still, surprisingly few results from animal models have been
      translated into clinical CIM management and treatments. The results obtained from
      specific animal models can be difficult to translate to the diverse range of CIM
      manifestations in patients, which vary according to the antineoplastic drugs,
      dose, underlying (cancer) disease, and patient characteristics (e.g., age,
      genetics, and body constitution). Another factor that hinders the direct use of
      results from animals is inadequate collaboration between basic science and
      clinical science in relation to CIM. Here, we briefly describe CIM
      pathophysiology, particularly the basic knowledge that has been obtained from CIM
      animal models. These model studies have indicated potential new preventive and
      ameliorating interventions, including supplementation with natural bioactive
      diets (e.g., milk fractions, colostrum, and plant extracts), nutrients (e.g.,
      polyunsaturated fatty acids, short-chain fatty acids, and glutamine), and growth
      factor peptides (e.g., transforming growth factor and glucagon-like peptide-2),
      as well as manipulations of the gut microbiota (e.g., prebiotics, probiotics, and
      antibiotics). Rodent CIM models allow well-controlled, in-depth studies of
      animals with or without tumors while pig models more easily make clinically
      relevant treatment regimens possible. In synergy, animal models of CIM provide
      the basic physiological understanding and the new ideas for treatment that are
      required to make competent decisions in clinical practice.

PMID- 29074484
TI  - Diurnal variations in intestinal barrier integrity and liver pathology in mice:
      implications for alcohol binge.
AB  - Recent studies suggest that circadian rhythms regulate intestinal barrier
      integrity, but it is not clear whether there are daily variations in barrier
      integrity. This study investigated daily variations in intestinal barrier
      integrity, including whether there are differences in alcohol-induced intestinal
      barrier dysfunction after an alcohol binge at different times of day and whether
      this is associated with concurrent liver injury. C57BL6/J male mice were fed a
      standard chow diet, an alcohol-containing liquid diet, or an alcohol control diet
      for 4 wk. During week 5 (i.e., on days 43-45), mice received three once-daily
      gavages of alcohol (6 g/kg) or the control (phosphate-buffered saline) at the
      same time each day. Immediately after the binge on the second day, intestinal
      permeability was assessed. Four hours after the third and final binge, mice were
      euthanized and tissue samples collected. The results demonstrated diet-specific
      and outcome-specific effects of time, alcohol, and/or time by alcohol
      interaction. Specifically, the alcohol binge robustly influenced markers of
      intestinal barrier integrity, and liver markers were robustly influenced by time
      of day. Only intestinal permeability (i.e., sucralose) demonstrated a significant
      effect of time and also showed a binge by time interaction, suggesting that the
      time of the alcohol binge influences colonic permeability. NEW & NOTEWORTHY This
      study investigated daily variations in intestinal barrier integrity, including
      whether there are differences in alcohol-induced intestinal barrier dysfunction
      after an alcohol binge at different times of day and whether this is associated
      with concurrent liver injury. We conclude that 1) alcohol binge significantly
      impacted markers of intestinal permeability, 2) time of day significantly
      affected liver outcomes, and 3) the time of day influenced colonic permeability.

PMID- 29074486
TI  - Metabolic markers of protein maldigestion after a 15N test meal in minipigs with
      pancreatic exocrine insufficiency.
AB  - The effect of pancreatic exocrine insufficiency (PEI) on protein malabsorption is
      little documented, partly due to methodological barriers. We aimed to validate
      biomarkers of protein malabsorption using a 15N test meal in a minipig model of
      PEI. Six pancreatic duct-ligated minipigs were used as a model of PEI and four
      nonoperated animals as a control. All animals were equipped with an ileocecal
      reentrant cannula. Minipigs were given a test meal containing [15N]casein. The
      PEI animals repeated the test three times, in the absence of any pancreatic
      enzymes, or after pancreatic substitution at two levels [ A or B: 7,500 or 75,000
      (lipase) and 388 or 3881 (protease) FIP U]. Ileal chyme, urine, and blood were
      collected postprandially. Nitrogen and 15N were measured in digestive and
      metabolic pools. We obtained a gradient of ileal protein digestibility from 29 +/
      11% in PEI to 89 +/- 6% in the controls and a dose- dependent response of
      enzymes. Insulin and gastric inhibitory polypeptide secretions were decreased by
      PEI, an effect that was counteracted with the enzymes at level B. The total
      recovery of 15N in urinary urea and plasma proteins was 14 +/- 5.1% in the
      control group and decreased to 5.5 +/- 2.1% by PEI. It was dose dependently
      restored by the treatment. Both 15N recovery in plasma and urine were correlated
      to protein digestibility. We confirm that the 15N transfer in those pools is a
      sensitive marker of protein malabsorption. Nevertheless, an optimization of the
      test meal conditions would be necessary in the view of implementing a clinical
      test. NEW & NOTEWORTHY We designed an intervention study to create a gradient of
      ileal protein digestibility in minipigs with pancreatic exocrine insufficiency
      and to validate reliable metabolic markers using a 15N oral meal test. 15N
      recovery in plasma proteins and to a higher extent in urine was sensitive to
      protein malabsorption. This test is minimally invasive and could be used to
      reveal protein malabsorption in patients.

PMID- 29074487
TI  - 12-Lipoxygenase and 12-hydroxyeicosatetraenoic acid regulate hypoxic angiogenesis
      and survival of pulmonary artery endothelial cells via PI3K/Akt pathway.
AB  - Dysfunction and injury of endothelial cells play critical roles in pulmonary
      arterial hypertension, including aberrant proliferation, suppressed apoptosis,
      and excessive angiogenesis. The 12-lipoxygenase and 12-hydroxyeicosatetraenoic
      acid pathway, which has been considered as a crucial mediator, elevates pulmonary
      vascular resistance and pulmonary arterial pressure. However, the mechanisms
      underlying the bioactivity of 12-hydroxyeicosatetraenoic acid in pulmonary
      vasculature, especially in endothelial cells, are still elusive. Thus we aim to
      determine the key role of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid in
      angiogenesis and survival of pulmonary artery endothelial cells and ascertain the
      signaling pathways participating in the pathological process. Here we establish
      that hypoxia increases the formation of endogenous 12-hydroxyeicosatetraenoic
      acid through stimulation of 12-lipoxygenase. Furthermore, we put forward new
      information that 12-hydroxyeicosatetraenoic acid promotes endothelial cell
      migration and tube formation, whereas it inhibits the serum deprivation-induced
      apoptotic responses under hypoxia. Particularly, the regulatory effects of 12
      lipoxygenase/12-hydroxyeicosatetraenoic acid on pulmonary artery endothelial
      cells, at least in part, depend on phosphatidylinositol 3-kinase (PI3K)/Akt
      signaling activation. Taken together, these results may have significant
      implications for understanding of pulmonary hypertension and offer a potential
      therapeutic concept focusing on the 12-lipoxygenase/12-hydroxyeicosatetraenoic
      acid signaling system.

PMID- 29074488
TI  - Endothelial HIF-2alpha contributes to severe pulmonary hypertension due to
      endothelial-to-mesenchymal transition.
AB  - Pulmonary vascular remodeling characterized by concentric wall thickening and
      intraluminal obliteration is a major contributor to the elevated pulmonary
      vascular resistance in patients with idiopathic pulmonary arterial hypertension
      (IPAH). Here we report that increased hypoxia-inducible factor 2alpha (HIF
      2alpha) in lung vascular endothelial cells (LVECs) under normoxic conditions is
      involved in the development of pulmonary hypertension (PH) by inducing
      endothelial-to-mesenchymal transition (EndMT), which subsequently results in
      vascular remodeling and occlusive lesions. We observed significant EndMT and
      markedly increased expression of SNAI, an inducer of EndMT, in LVECs from
      patients with IPAH and animals with experimental PH compared with normal
      controls. LVECs isolated from IPAH patients had a higher level of HIF-2alpha than
      that from normal subjects, whereas HIF-1alpha was upregulated in pulmonary
      arterial smooth muscle cells (PASMCs) from IPAH patients. The increased HIF
      2alpha level, due to downregulated prolyl hydroxylase domain protein 2 (PHD2), a
      prolyl hydroxylase that promotes HIF-2alpha degradation, was involved in enhanced
      EndMT and upregulated SNAI1/2 in LVECs from patients with IPAH. Moreover,
      knockdown of HIF-2alpha (but not HIF-1alpha) with siRNA decreases both SNAI1 and
      SNAI2 expression in IPAH-LVECs. Mice with endothelial cell (EC)-specific knockout
      (KO) of the PHD2 gene, egln1 (egln1EC-/-), developed severe PH under normoxic
      conditions, whereas Snai1/2 and EndMT were increased in LVECs of egln1EC-/- mice.
      EC-specific KO of the HIF-2alpha gene, hif2a, prevented mice from developing
      hypoxia-induced PH, whereas EC-specific deletion of the HIF-1alpha gene, hif1a,
      or smooth muscle cell (SMC)-specific deletion of hif2a, negligibly affected the
      development of PH. Also, exposure to hypoxia for 48-72 h increased protein level
      of HIF-1alpha in normal human PASMCs and HIF-2alpha in normal human LVECs. These
      data indicate that increased HIF-2alpha in LVECs plays a pathogenic role in the
      development of severe PH by upregulating SNAI1/2, inducing EndMT, and causing
      obliterative pulmonary vascular lesions and vascular remodeling.

PMID- 29074491
TI  - Simvastatin decreases hyperbaric oxygen-induced acute lung injury by upregulating
      eNOS.
AB  - Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      competitive inhibitors, not only lower blood cholesterol but also exert
      pleiotropic and beneficial effects in various diseases. However, the effects of
      statins on acute lung injury (ALI) induced by hyperbaric oxygen (HBO) have not
      been investigated. The present study is the first to investigate the effects of
      simvastatin in ALI induced by HBO in 8- to 9-wk-old C57BL/6 mice exposed to 0.23
      MPa [=2.3 atmosphere absolute (ATA)] hyperoxia (>=95% O2) for 6 h. Mice were
      either given simvastatin (20 mg.kg.-1.day-1) in saline or a saline vehicle for 3
      days before oxygen exposure. Lung tissue, serum, and bronchoalveolar lavage fluid
      (BALF) were collected for analysis of proapoptotic proteins, low-density
      lipoprotein cholesterol (LDL-C) levels, and lung inflammation. Simvastatin
      treatment significantly reduced lung permeability, serum LDL-C levels, tissue
      apoptosis, and inflammation. However, simvastatin treatment had no effect on
      antioxidant enzyme activity, nicotinamide adenine dinucleotide phosphate oxidase
      4 (NADPH4) expression, and Akt phosphorylation levels. Furthermore, we
      investigated the role of endothelial nitric oxide synthase (eNOS) in simvastatin
      protection through inhibiting eNOS activity with NG-nitro-l-arginine methyl ester
      (l-NAME; 20 mg/kg). Results showed that the beneficial effects of simvastatin on
      ALI induced by HBO (antiinflammatory, antiapoptotic, lipid lowering, and
      reduction in lung permeability) were reversed. These results showed that
      simvastatin curbs HBO-induced lung edema, permeability, inflammation, and
      apoptosis via upregulating eNOS expression and that simvastatin could be an
      effective therapy to treat prolonged HBO exposure.

PMID- 29074489
TI  - Autophagy and the unfolded protein response promote profibrotic effects of TGF
      beta1 in human lung fibroblasts.
AB  - Idiopathic pulmonary fibrosis (IPF) is a lethal fibrotic lung disease in adults
      with limited treatment options. Autophagy and the unfolded protein response
      (UPR), fundamental processes induced by cell stress, are dysregulated in lung
      fibroblasts and epithelial cells from humans with IPF. Human primary cultured
      lung parenchymal and airway fibroblasts from non-IPF and IPF donors were
      stimulated with transforming growth factor-beta1 (TGF-beta1) with or without
      inhibitors of autophagy or UPR (IRE1 inhibitor). Using immunoblotting, we
      monitored temporal changes in abundance of protein markers of autophagy
      (LC3betaII and Atg5-12), UPR (BIP, IRE1alpha, and cleaved XBP1), and fibrosis
      (collagen 1alpha2 and fibronectin). Using fluorescent immunohistochemistry, we
      profiled autophagy (LC3betaII) and UPR (BIP and XBP1) markers in human non-IPF
      and IPF lung tissue. TGF-beta1-induced collagen 1alpha2 and fibronectin protein
      production was significantly higher in IPF lung fibroblasts compared with lung
      and airway fibroblasts from non-IPF donors. TGF-beta1 induced the accumulation of
      LC3betaII in parallel with collagen 1alpha2 and fibronectin, but autophagy marker
      content was significantly lower in lung fibroblasts from IPF subjects. TGF-beta1
      induced collagen and fibronectin biosynthesis was significantly reduced by
      inhibiting autophagy flux in fibroblasts from the lungs of non-IPF and IPF
      donors. Conversely, only in lung fibroblasts from IPF donors did TGF-beta1 induce
      UPR markers. Treatment with an IRE1 inhibitor decreased TGF-beta1-induced
      collagen 1alpha2 and fibronectin biosynthesis in IPF lung fibroblasts but not
      those from non-IPF donors. The IRE1 arm of the UPR response is uniquely induced
      by TGF-beta1 in lung fibroblasts from human IPF donors and is required for
      excessive biosynthesis of collagen and fibronectin in these cells.

PMID- 29074490
TI  - Lung disease phenotypes caused by overexpression of combinations of alpha-, beta
      , and gamma-subunits of the epithelial sodium channel in mouse airways.
AB  - The epithelial Na+ channel (ENaC) regulates airway surface hydration. In mouse
      airways, ENaC is composed of three subunits, alpha, beta, and gamma, which are
      differentially expressed (alpha > beta > gamma). Airway-targeted overexpression
      of the beta subunit results in Na+ hyperabsorption, causing airway surface
      dehydration, hyperconcentrated mucus with delayed clearance, lung inflammation,
      and perinatal mortality. Notably, mice overexpressing the alpha- or gamma-subunit
      do not exhibit airway Na+ hyperabsorption or lung pathology. To test whether
      overexpression of multiple ENaC subunits produced Na+ transport and disease
      severity exceeding that of betaENaC-Tg mice, we generated double (alphabeta,
      alphagamma, betagamma) and triple (alphabetagamma) transgenic mice and
      characterized their lung phenotypes. Double alphagammaENaC-Tg mice were
      indistinguishable from WT littermates. In contrast, double betagammaENaC-Tg mice
      exhibited airway Na+ absorption greater than that of betaENaC-Tg mice, which was
      paralleled by worse survival, decreased mucociliary clearance, and more severe
      lung pathology. Double alphabetaENaC-Tg mice exhibited Na+ transport rates
      comparable to those of betaENaC-Tg littermates. However, alphabetaENaC-Tg mice
      had poorer survival and developed severe parenchymal consolidation. In situ
      hybridization (RNAscope) analysis revealed both alveolar and airway alphaENaC-Tg
      overexpression. Triple alphabetagammaENaC-Tg mice were born in Mendelian
      proportions but died within the first day of life, and the small sample size
      prevented analyses of cause(s) of death. Cumulatively, these results indicate
      that overexpression of betaENaC is rate limiting for generation of pathological
      airway surface dehydration. Notably, airway co-overexpression of beta- and
      gammaENaC had additive effects on Na+ transport and disease severity, suggesting
      dose dependency of these two variables.

PMID- 29074493
TI  - Comparative analysis of autofluorescence and OCT angiography in Stargardt
      disease.
AB  - AIMS: To characterise the vasculature of the retina in patients with Stargardt
      disease (STGD) using optical coherence tomography angiography (OCTA) and to
      compare these functional findings with fundus autofluorescence (FAF) imaging.
      METHODS: This observational study included consecutive patients with STGD. The
      choriocapillaris (CC) layer was analysed on OCTA and retinal pigment epithelium
      (RPE) changes were assessed on FAF. Areas of CC and RPE impairment were
      quantified and correlated. RESULTS: Twenty-two patients suffering from different
      stages of STGD were enrolled. OCTA revealed a vascular rarefaction with vascular
      prominence in 15 (35%) eyes while the remaining cases had pure vascular
      rarefaction. On FAF imaging, 25 (58%) eyes had a peripapillary halo, a
      hypofluorescent lesion in foveal area and the presence of both hypofluorescent
      and hyperfluorescent changes. On FAF imaging, the average area of RPE impairment
      was 6.7+/-4.4 mm2 while on OCTA a hypointense area of 4.2+/-3.6 mm2 was shown at
      the level of the CC layer. Mann-Whitney U test showed a statistically significant
      difference in terms of lesion extension between these two findings (p=0.004).
      CONCLUSION: RPE damage on FAF appears to be significantly larger than CC layer
      vessel loss on OCTA, which suggests that RPE damage might precede that of CC.

PMID- 29074492
TI  - Autophagy inhibitor 3-methyladenine protects against endothelial cell barrier
      dysfunction in acute lung injury.
AB  - Autophagy is an evolutionarily conserved cellular process that facilitates the
      continuous recycling of intracellular components (organelles and proteins) and
      provides an alternative source of energy when nutrients are scarce. Recent
      studies have implicated autophagy in many disorders, including pulmonary
      diseases. However, the role of autophagy in endothelial cell (EC) barrier
      dysfunction and its relevance in the context of acute lung injury (ALI) remain
      uncertain. Here, we provide evidence that autophagy is a critical component of EC
      barrier disruption in ALI. Using an aerosolized bacterial lipopolysaccharide
      (LPS) inhalation mouse model of ALI, we found that administration of the
      autophagy inhibitor 3-methyladenine (3-MA), either prophylactically or
      therapeutically, markedly reduced lung vascular leakage and tissue edema. 3-MA
      was also effective in reducing the levels of proinflammatory mediators and lung
      neutrophil sequestration induced by LPS. To test the possibility that autophagy
      in EC could contribute to lung vascular injury, we addressed its role in the
      mechanism of EC barrier disruption. Knockdown of ATG5, an essential regulator of
      autophagy, attenuated thrombin-induced EC barrier disruption, confirming the
      involvement of autophagy in the response. Similarly, exposure of cells to 3-MA,
      either before or after thrombin, protected against EC barrier dysfunction by
      inhibiting the cleavage and loss of vascular endothelial cadherin at adherens
      junctions, as well as formation of actin stress fibers. 3-MA also reversed LPS
      induced EC barrier disruption. Together, these data imply a role of autophagy in
      lung vascular injury and reveal the protective and therapeutic utility of 3-MA
      against ALI.

PMID- 29074494
TI  - Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by
      adaptive optics retinal imaging.
AB  - PURPOSE: Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD)
      have been identified. However, the mechanisms by which genetic mutations lead to
      cellular loss in human disease remain poorly understood. Here we combine
      genotyping with high-resolution adaptive optics retinal imaging to elucidate the
      retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect
      in the GUCA1A gene. METHODS: Nine affected members of a four-generation AD-CRD
      pedigree and three unaffected first-degree relatives underwent clinical
      examinations including visual acuity, fundus examination, Goldmann perimetry,
      spectral domain optical coherence tomography and electroretinography. Genome-wide
      scan followed by bidirectional sequencing was performed on all affected
      participants. High-resolution imaging using a custom adaptive optics scanning
      light ophthalmoscope (AOSLO) was performed for selected participants. RESULTS:
      Clinical evaluations showed a range of disease severity from normal fundus
      appearance in teenaged patients to pronounced macular atrophy in older patients.
      Molecular genetic testing showed a mutation in in GUCA1A segregating with
      disease. AOSLO imaging revealed that of the two teenage patients with mild
      disease, one had severe disruption of the photoreceptor mosaic while the other
      had a normal cone mosaic. CONCLUSIONS: AOSLO imaging demonstrated variability in
      the pattern of cone and rod cell loss between two teenage cousins with early AD
      CRD, who had similar clinical features and had the identical disease-causing
      mutation in GUCA1A. This finding suggests that a mutation in GUCA1A does not lead
      to the same degree of AD-CRD in all patients. Modifying factors may mitigate or
      augment disease severity, leading to different retinal cellular phenotypes.

PMID- 29074495
TI  - Outcome of anti-vascular endothelial growth factor therapy for neovascular age
      related macular degeneration in real-life setting.
AB  - AIMS: To evaluate outcome of anti-vascular endothelial growth factor (VEGF)
      therapy for the treatment of neovascular age-related macular degeneration (nAMD)
      in the real-life setting and to compare incidence of ocular serious adverse
      events (SAE) after injections administered by nurses and physicians. METHODS:
      Retrospective, single-centre study. Medical records of patients receiving anti
      VEGF treatment for nAMD between 2008 and 2013 with three-loading-dose regimen
      were evaluated. Outcome measures were baseline visual acuity (VA), change in VA,
      number of intravitreal injections, incidence of ocular SAE and patients' baseline
      characteristics affecting VA change. In addition, the number of injections per
      1000 citizens living in the serving area and per individuals over 65 years old
      were estimated. RESULTS: 1349 eyes in 1117 patients received a total of 11 562
      intravitreal anti-VEGF injections. Twenty-one per cent of patients received
      treatment for both eyes. The mean baseline Snellen VA was 0.32. The mean change
      of VA from baseline was +2, +2 and +/-0 Early Treatment Diabetic Retinopathy
      Study letters and the mean numbers of injections were 5.7, 4.7 and 4.9 at years
      1, 2 and 3, respectively. There was a negative correlation between baseline VA
      and change of VA. Incidence of endophthalmitis was 0.086%. No difference in the
      incidence of ocular SAE was identified between injections given by nurses or by
      physicians. The number of intravitreal injections per all citizens was 9 per 1000
      inhabitants and 45 per 1000 inhabitants over 65 years. CONCLUSION: The VA was
      maintained at the baseline level (+/-0 letters) with the mean of 15.3 anti-VEGF
      injections in real-world clinical practice during 3-year follow-up.

PMID- 29074497
TI  - Example of monitoring measurements in a virtual eye clinic using 'big data'.
AB  - AIM: To assess the equivalence of measurement outcomes between patients attending
      a standard glaucoma care service, where patients see an ophthalmologist in a face
      to-face setting, and a glaucoma monitoring service (GMS). METHODS: The average
      mean deviation (MD) measurement on the visual field (VF) test for 250 patients
      attending a GMS were compared with a 'big data' repository of patients attending
      a standard glaucoma care service (reference database). In addition, the speed of
      VF progression between GMS patients and reference database patients was compared.
      Reference database patients were used to create expected outcomes that GMS
      patients could be compared with. For GMS patients falling outside of the expected
      limits, further analysis was carried out on the clinical management decisions for
      these patients. RESULTS: The average MD of patients in the GMS ranged from +1.6dB
      to -18.9dB between two consecutive appointments at the clinic. In the first
      analysis, 12 (4.8%; 95% CI 2.5% to 8.2%) GMS patients scored outside the 90%
      expected values based on the reference database. In the second analysis, 1.9%
      (95% CI 0.4% to 5.4%) GMS patients had VF changes outside of the expected 90%
      limits. CONCLUSIONS: Using 'big data' collected in the standard glaucoma care
      service, we found that patients attending a GMS have equivalent outcomes on the
      VF test. Our findings provide support for the implementation of virtual
      healthcare delivery in the hospital eye service.

PMID- 29074496
TI  - Treatment of Advanced Glaucoma Study: a multicentre randomised controlled trial
      comparing primary medical treatment with primary trabeculectomy for people with
      newly diagnosed advanced glaucoma-study protocol.
AB  - BACKGROUND: Presentation with advanced glaucoma is the major risk factor for
      lifetime blindness. Effective intervention at diagnosis is expected to minimise
      risk of further visual loss in this group of patients. AIM: To compare clinical
      and cost-effectiveness of primary medical management compared with primary
      surgery for people presenting with advanced open-angle glaucoma (OAG). METHODS:
      Design: A prospective, pragmatic multicentre randomised controlled trial (RCT).
      SETTING: Twenty-seven UK hospital eye services. PARTICIPANTS: Four hundred and
      forty patients presenting with advanced OAG, according to the Hodapp-Parish
      Anderson classification of visual field loss. INTERVENTION: Participants will be
      randomised to medical treatment or augmented trabeculectomy (1:1 allocation
      minimised by centre and presence of advanced disease in both eyes). MAIN OUTCOME
      MEASURES: The primary outcome is vision-related quality of life measured by the
      National Eye Institute-Visual Function Questionnaire-25 at 24 months. Secondary
      outcomes include generic EQ-5D-5L, Health Utility Index-3 and glaucoma-related
      health status (Glaucoma Utility Index), patient experience, visual field measured
      by mean deviation value, logarithm of the mean angle of resolution visual acuity,
      intraocular pressure, adverse events, standards for driving and eligibility for
      blind certification. Incremental cost per quality-adjusted life-year (QALY) based
      on EQ-5D-5L and glaucoma profile instrument will be estimated. RESULTS: The study
      will report the comparative effectiveness and cost-effectiveness of medical
      treatment against augmented trabeculectomy in patients presenting with advanced
      glaucoma in terms of patient-reported health and visual function, clinical
      outcomes and incremental cost per QALY at 2 years. CONCLUSIONS: Treatment of
      Advanced Glaucoma Study will be the first RCT reporting outcomes from the
      perspective of those with advanced glaucoma. TRIAL REGISTRATION NUMBER:
      ISRCTN56878850, Pre-results.

PMID- 29074499
TI  - Endogenous fibrinolysis facilitates clot retraction in vivo.
AB  - Clot retraction refers to the process whereby activated platelets transduce
      contractile forces onto the fibrin network of a thrombus, which over time
      increases clot density and decreases clot size. This process is considered
      important for promoting clot stability and maintaining blood vessel patency.
      Insights into the mechanisms regulating clot retraction at sites of vascular
      injury have been hampered by a paucity of in vivo experimental models. By pairing
      localized vascular injury with thrombin microinjection in the mesenteric
      circulation of mice, we have demonstrated that the fibrin network of thrombi
      progressively compacts over a 2-hour period. This was a genuine retraction
      process, as treating thrombi with blebbistatin to inhibit myosin IIa-mediated
      platelet contractility prevented shrinkage of the fibrin network. Real-time
      confocal analysis of fibrinolysis after recombinant tissue-type plasminogen
      activator (tPA) administration revealed that incomplete proteolysis of fibrin
      polymers markedly facilitated clot retraction. Similarly, inhibiting endogenous
      fibrinolysis with tranexamic acid reduced retraction of fibrin polymers in vivo.
      In vitro clot retraction experiments indicated that subthreshold doses of tPA
      facilitated clot retraction through a plasmin-dependent mechanism. These effects
      correlated with changes in the elastic modulus of fibrin clots. These findings
      define the endogenous fibrinolytic system as an important regulator of clot
      retraction, and show that promoting clot retraction is a novel and complementary
      means by which fibrinolytic enzymes can reduce thrombus size.

PMID- 29074498
TI  - Ferritin is secreted via 2 distinct nonclassical vesicular pathways.
AB  - Ferritin turnover plays a major role in tissue iron homeostasis, and ferritin
      malfunction is associated with impaired iron homeostasis and neurodegenerative
      diseases. In most eukaryotes, ferritin is considered an intracellular protein
      that stores iron in a nontoxic and bioavailable form. In insects, ferritin is a
      classically secreted protein and plays a major role in systemic iron
      distribution. Mammalian ferritin lacks the signal peptide for classical
      endoplasmic reticulum-Golgi secretion but is found in serum and is secreted via a
      nonclassical lysosomal secretion pathway. This study applied bioinformatics and
      biochemical tools, alongside a protein trafficking mouse models, to characterize
      the mechanisms of ferritin secretion. Ferritin trafficking via the classical
      secretion pathway was ruled out, and a 2:1 distribution of intracellular ferritin
      between membrane-bound compartments and the cytosol was observed, suggesting a
      role for ferritin in the vesicular compartments of the cell. Focusing on
      nonclassical secretion, we analyzed mouse models of impaired endolysosomal
      trafficking and found that ferritin secretion was decreased by a BLOC-1 mutation
      but increased by BLOC-2, BLOC-3, and Rab27A mutations of the cellular trafficking
      machinery, suggesting multiple export routes. A 13-amino-acid motif unique to
      ferritins that lack the secretion signal peptide was identified on the BC-loop of
      both subunits and plays a role in the regulation of ferritin secretion. Finally,
      we provide evidence that secretion of iron-rich ferritin was mediated via the
      multivesicular body-exosome pathway. These results enhance our understanding of
      the mechanism of ferritin secretion, which is an important piece in the puzzle of
      tissue iron homeostasis.

PMID- 29074500
TI  - Cytokine release syndrome associated with chimeric-antigen receptor T-cell
      therapy: clinicopathological insights.

PMID- 29074501
TI  - Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2
      consortium trial.
AB  - Most patients with follicular lymphoma (FL) experience multiple relapses
      necessitating subsequent lines of therapy. Ibrutinib, a Bruton tyrosine kinase
      (BTK) inhibitor approved for the treatment of several B-cell malignancies, showed
      promising activity in FL in a phase 1 study. We report the results of a phase 2
      trial evaluating ibrutinib in recurrent FL. Forty patients with recurrent FL were
      treated with ibrutinib 560 mg/d until progression or intolerance. The primary end
      point was overall response rate (ORR). Exploratory analyses included correlations
      of outcome with recurrent mutations identified in a cancer gene panel that used
      next-generation sequencing in pretreatment biopsies from 31 patients and results
      of early interim positron emission tomography/computed tomography scans in 20
      patients. ORR was 37.5% with a complete response rate of 12.5%, median
      progression-free survival (PFS) of 14 months, and 2-year PFS of 20.4%. Response
      rates were significantly higher among patients whose disease was sensitive to
      rituximab (52.6%) compared with those who were rituximab refractory (16.7%) (P =
      .04). CARD11 mutations were present in 16% of patients (5 of 31) and predicted
      resistance to ibrutinib with only wild-type patients responding (P = .002).
      Maximum standardized uptake value at cycle 1 day 8 correlated with response and
      PFS. Ibrutinib was well-tolerated with a toxicity profile similar to labeled
      indications. Ibrutinib is a well-tolerated treatment with modest activity in
      relapsed FL. Evaluation of BTK inhibitors in earlier lines of therapy may be
      warranted on the basis of improved response rates in rituximab-sensitive disease.
      Somatic mutations such as CARD11 may have an impact on response to ibrutinib, may
      inform clinical decisions, and should be evaluated in larger data sets. This
      trial was registered at www.clinicaltrials.gov as #NCT01849263.

PMID- 29074502
TI  - EBV latent membrane protein 2A orchestrates p27kip1 degradation via Cks1 to
      accelerate MYC-driven lymphoma in mice.
AB  - Epstein-Barr virus (EBV) establishes lifelong infection in B lymphocytes of most
      human hosts and is associated with several B lymphomas. During latent infection,
      EBV encodes latent membrane protein 2A (LMP2A) to promote the survival of B cells
      by mimicking host B-cell receptor signaling. By studying the roles of LMP2A
      during lymphoma development in vivo, we found that LMP2A mediates rapid MYC
      driven lymphoma onset by allowing B cells to bypass MYC-induced apoptosis
      mediated by the p53 pathway in our transgenic mouse model. However, the
      mechanisms used by LMP2A to facilitate transformation remain elusive. In this
      study, we demonstrate a key role of LMP2A in promoting hyperproliferation of B
      cells by enhancing MYC expression and MYC-dependent degradation of the p27kip1
      tumor suppressor. Loss of the adaptor protein cyclin-dependent kinase regulatory
      subunit 1 (Cks1), a cofactor of the SCFSkp2 ubiquitin ligase complex and a
      downstream target of MYC, increases p27kip1 expression during a premalignant
      stage. In mice that express LMP2A, Cks1 deficiency reduces spleen weights,
      restores B-cell follicle formation, impedes cell cycle progression of pretumor B
      cells, and eventually prolongs MYC-driven tumor onset. This study demonstrates
      that LMP2A uses the role of MYC in the cell cycle, particularly in the p27kip1
      degradation process, to accelerate lymphomagenesis in vivo. Thus, our results
      reveal a novel mechanism of EBV in diverting the functions of MYC in malignant
      transformation and provide a rationale for targeting EBV's roles in cell cycle
      modulation.

PMID- 29074505
TI  - Telephone-based collaborative care is an effective approach for treating anxiety
      in primary care patients.

PMID- 29074504
TI  - Derivation and Validation of the CREST Model for Very Early Prediction of
      Circulatory Etiology Death in Patients Without ST-Segment-Elevation Myocardial
      Infarction After Cardiac Arrest.
AB  - BACKGROUND: No practical tool quantitates the risk of circulatory-etiology death
      (CED) immediately after successful cardiopulmonary resuscitation in patients
      without ST-segment-elevation myocardial infarction. We developed and validated a
      prediction model to rapidly determine that risk and facilitate triage to
      individualized treatment pathways. METHODS: With the use of INTCAR (International
      Cardiac Arrest Registry), an 87-question data set representing 44 centers in the
      United States and Europe, patients were classified as having had CED or a
      combined end point of neurological-etiology death or survival. Demographics and
      clinical factors were modeled in a derivation cohort, and backward stepwise
      logistic regression was used to identify factors independently associated with
      CED. We demonstrated model performance using area under the curve and the Hosmer
      Lemeshow test in the derivation and validation cohorts, and assigned a simplified
      point-scoring system. RESULTS: Among 638 patients in the derivation cohort, 121
      (18.9%) had CED. The final model included preexisting coronary artery disease
      (odds ratio [OR], 2.86; confidence interval [CI], 1.83-4.49; P<=0.001),
      nonshockable rhythm (OR, 1.75; CI, 1.10-2.77; P=0.017), initial ejection
      fraction<30% (OR, 2.11; CI, 1.32-3.37; P=0.002), shock at presentation (OR, 2.27;
      CI, 1.42-3.62; P<0.001), and ischemic time >25 minutes (OR, 1.42; CI, 0.90-2.23;
      P=0.13). The derivation model area under the curve was 0.73, and Hosmer-Lemeshow
      test P=0.47. Outcomes were similar in the 318-patient validation cohort (area
      under the curve 0.68, Hosmer-Lemeshow test P=0.41). When assigned a point for
      each associated factor in the derivation model, the average predicted versus
      observed probability of CED with a CREST score (coronary artery disease, initial
      heart rhythm, low ejection fraction, shock at the time of admission, and ischemic
      time >25 minutes) of 0 to 5 was: 7.1% versus 10.2%, 9.5% versus 11%, 22.5% versus
      19.6%, 32.4% versus 29.6%, 38.5% versus 30%, and 55.7% versus 50%. CONCLUSIONS:
      The CREST model stratified patients immediately after resuscitation according to
      risk of a circulatory-etiology death. The tool may allow for estimation of
      circulatory risk and improve the triage of survivors of cardiac arrest without ST
      segment-elevation myocardial infarction at the point of care.

PMID- 29074503
TI  - The ins and outs of endoplasmic reticulum-controlled lipid biosynthesis.
AB  - Endoplasmic reticulum (ER)-localized enzymes synthesize the vast majority of
      cellular lipids. The ER therefore has a major influence on cellular lipid biomass
      and balances the production of different lipid categories, classes, and species.
      Signals from outside and inside the cell are directed to ER-localized enzymes,
      and lipid enzyme activities are defined by the integration of internal,
      homeostatic, and external information. This allows ER-localized lipid synthesis
      to provide the cell with membrane lipids for growth, proliferation, and
      differentiation-based changes in morphology and structure, and to maintain
      membrane homeostasis across the cell. ER enzymes also respond to physiological
      signals to drive carbohydrates and nutritionally derived lipids into energy
      storing triglycerides. In this review, we highlight some key regulatory
      mechanisms that control ER-localized enzyme activities in animal cells. We also
      discuss how they act in concert to maintain cellular lipid homeostasis, as well
      as how their dysregulation contributes to human disease.

PMID- 29074506
TI  - Tricks of the trade: time management tips for newly qualified doctors.
AB  - BACKGROUND: The transition from medical student to doctor is an important
      milestone. The discovery that their time is no longer their own and that the
      demands of their job are greater than the time they have available is extremely
      challenging. METHODS: At a recent surgical boot camp training programme, 60 first
      year surgical trainees who had just completed their internship were invited to
      reflect on the lessons learnt regarding effective time management and to
      recommend tips for their newly qualified colleagues. They were asked to identify
      clinical duties that were considered urgent and important using the time
      management matrix and the common time traps encountered by newly qualified
      doctors. RESULTS: The surgical trainees identified several practical tips that
      ranged from writing a priority list to working on relationships within the team.
      These tips are generic and so applicable to all newly qualified medial doctors.
      POTENTIAL IMPLICATION: We hope that awareness of these tips from the outset as
      against learning them through experience will greatly assist newly qualified
      doctors.

PMID- 29074507
TI  - Systematic review of interventions for improving the performance of community
      health workers in low-income and middle-income countries.
AB  - OBJECTIVE: To systematically review and critically appraise the evidence for the
      effects of interventions to improve the performance of community health workers
      (CHWs) for community-based primary healthcare in low- and middle-income
      countries. DESIGN: Systematic review following Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines. METHODS: 19 electronic databases
      were searched with a highly sensitive prespecified strategy and the grey
      literature examined, completed July 2016. Randomised controlled trials evaluating
      interventions to improve CHW performance in low- and middle-income countries were
      included and appraised for risk of bias. Outcomes were biological and behavioural
      patient outcomes (primary), use of health services, quality of care provided by
      CHWs and CHW retention (secondary). RESULTS: Two reviewers screened 8082 records;
      14 evaluations were included. Due to heterogeneity and lack of clear outcome
      data, no meta-analysis was conducted. Results were presented in a narrative
      summary. The review found one study showing no effect on the biological outcomes
      of interest, though these moderate quality data may not be indicative of all
      biological outcomes. It also found moderate quality evidence of the efficacy of
      performance improvement interventions for (1) improving behavioural outcomes for
      patients, (2) improving use of services by increasing the absolute number of
      patients who access services and, perhaps, better identifying those who would
      benefit from such services and (3) improving CHW quality of care in terms of
      upstream measures like completion of prescribed activities and downstream
      measures like adherence to treatment protocols. Nearly half of studies were
      compound interventions, making it difficult to isolate the effects of individual
      performance improvement intervention components, though four specific strategies
      pertaining to recruitment, supervision, incentivisation and equipment were
      identified. CONCLUSIONS: Variations in recruitment, supervision, incentivisation
      and equipment may improve CHW performance. Practitioners should, however, assess
      the relevance and feasibility of these strategies in their health setting prior
      to implementation. Component selection experiments on a greater range of
      interventions to improve performance ought to be conducted.

PMID- 29074509
TI  - Cognitive complexity of clients and counsellors during motivation-based treatment
      for smoking cessation: an observational study on occasional smokers in a US
      college sample.
AB  - OBJECTIVE: Motivational interviewing (MI) is a widely used and promising
      treatment approach for aiding in smoking cessation. The present observational
      study adds to other recent research on why and when MI works by investigating a
      new potential mechanism: integrative complexity. SETTING: The study took place in
      college fraternity and sorority chapters at one large midwestern university.
      PARTICIPANTS: Researchers transcribed MI counselling sessions from a previous
      randomised controlled trial focused on tobacco cessation among college students
      and subsequently scored clients' and counsellors' discussions across four
      counselling sessions for integrative complexity. INTERVENTIONS: This is an
      observational secondary analysis of a randomised controlled trial that tested the
      effectiveness of MI. We analysed the relationship between integrative complexity
      and success at quitting smoking in the trial. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Success in quitting smoking:Participants were categorised into two
      outcome groups (successful quitters vs failed attempters), created based on
      dichotomous outcomes on two standard variables: (1) self-reported attempts to
      quit and (2) number of days smoked via timeline follow-back assessment procedures
      that use key events in participants' lives to prompt their recall of smoking.
      RESULTS: We found (1) significantly higher complexity overall for participants
      who tried to quit but failed compared with successful quitters (standardised
      beta=0.36, p<0.001, (Lower Confidence Interval.)LCI=0.16, (Upper Confidence
      Interval) UCI=0.47) and (2) the predictive effect of complexity on outcome
      remains when controlling for standard motivational and demographic variables
      (partial r(102)=-0.23, p=0.022). CONCLUSIONS: Taken together, these results
      suggest that cognitive complexity is uniquely associated with successful quitting
      in MI controlled trials, and thus may be an important variable to more fully
      explore during treatment.

PMID- 29074508
TI  - Sexual orientation identity and tobacco and hazardous alcohol use: findings from
      a cross-sectional English population survey.
AB  - OBJECTIVES: To assess the association between tobacco and hazardous alcohol use
      and sexual orientation and whether such an association could be explained by
      other sociodemographic characteristics. DESIGN: Cross-sectional household survey
      conducted in 2014-2016. SETTING: England, UK. PARTICIPANTS: Representative
      English population sample (pooled n=43 866). MAIN OUTCOMES: Sexual orientation
      identity (lesbian/gay, bisexual, heterosexual, prefer-not-to-say); current
      tobacco and hazardous alcohol use (defined as Alcohol Use Disorders
      Identification Test Score >=8). All outcomes were self-reported. RESULTS: Due to
      interactions between sexual orientation and gender for substance use, analyses
      were stratified by gender. Tobacco use prevalence was significantly higher among
      lesbian/gay (women: 24.9%, 95% CI 19.2% to 32.6%; men: 25.9%, 95% CI 21.3% to
      31.0%) and bisexual participants (women: 32.4%, 95% CI 25.9% to 39.6%; men:
      30.7%, 95% CI 23.7% to 30.7%) and significantly lower for prefer-not-to-say
      participants in women (15.5%, 95% CI 13.5% to 17.8%) but not men (22.7%, 95% CI
      20.3% to 25.3%) compared with heterosexual participants (women: 17.5%, 95% CI
      17.0% to 18.0%; men: 20.4%, 95% CI 19.9% to 21.0%; p<0.001 for omnibus test).
      Similarly, hazardous alcohol use was significantly more prevalent for lesbian/gay
      (women: 19.0%, 95% CI 14.0% to 25.3%; men: 30.0%, 25.2%-35.3%) and bisexual
      participants (women: 24.4%, 95% CI 18.7% to 31.3%; men: 24.3%, 95% CI 17.9% to
      32.1%) and lower for prefer-not-to-say participants (women: 4.1%, 95% CI 3.0% to
      5.4%; men: 13.7%; 95% CI 11.8% to 16.0%) compared with heterosexuals (women:
      8.3%, 95% CI 7.9% to 8.7%; men: 18.4%, 95% CI 17.9% to 18.9%; p<0.001 for omnibus
      test). However, after adjusting for sociodemographic confounders, tobacco use was
      similar across all sexual orientation groups among both women and men. By
      contrast, sexual orientation differences in hazardous alcohol use remained even
      after adjustment among women but not for bisexual and gay men. CONCLUSIONS: In
      England, higher rates of tobacco use among sexual minority men and women appear
      to be attributable to other sociodemographic factors. Higher rates of hazardous
      alcohol use among sexual minority men may also be attributable to these factors,
      whereas this is not the case for sexual minority women.

PMID- 29074510
TI  - Sex differences in survival of patients with type 2 diabetes in primary care
      (ZODIAC-50).
AB  - OBJECTIVE: To investigate sex differences in survival of primary care treated
      patients with type 2 diabetes (T2D) in the Netherlands. SETTING: Primary care.
      PARTICIPANTS: A total of 1815 patients who participated in a prospective
      observational cohort study (Zwolle Outpatient Diabetes Project Integrating
      Available Care (ZODIAC)) were included of which 56% was female. Inclusion took
      place in 1998, 1999 and 2001. Vital status was assessed in 2013. MAIN OUTCOME
      MEASURE: Relative survival of men and women with T2D. The relative survival rate
      was expressed as the ratio of observed survival of patients divided by the
      survival of the general population in the Netherlands with comparable age.
      RESULTS: After 14 years, 888 (49%) patients had died. The relative survival rate
      was 0.88 (0.81-0.94) for men and 0.82 (0.76-0.87) for women with T2D after 14
      years (p value for difference between sexes=0.169). In patients without a history
      of cardiovascular diseases (CVD), the relative survival was 0.99 (0.94-1.05) in
      men and 0.92 (0.87-0.97) in women (p value for difference between sexes=0.046).
      CONCLUSIONS: The survival of men and women with T2D was 12% and 18% lower,
      respectively, after 14 years of follow-up compared with men and women in the
      general population. This corresponds to a decrease in median survival of 2.2 and
      3.5 years in men and women, respectively. Only for patients with T2D without a
      history of CVD, a significantly lower relative survival in women compared with
      men with T2D was found.

PMID- 29074511
TI  - Bridging knowledge, policies and practices across the ageing and disability
      fields: a protocol for a scoping review to inform the development of a taxonomy.
AB  - INTRODUCTION: Bridging is a term used to describe activities, or tasks, used to
      promote collaboration and knowledge exchange across fields. This paper reports
      the protocol for a scoping review which aims to identify and characterise peer
      reviewed evidence describing bridging activities, between the ageing and
      disability fields. The purpose is to clarify the concepts underpinning bridging
      to inform the development of a taxonomy, and identify research strengths and
      gaps. METHODS: A scoping review will be conducted. We will search Medline,
      Cumulative Index to Nursing and Allied Health Literature, Embase, PsycInfo,
      Sociological Abstracts and the Cochrane Library, to identify peer reviewed
      publications (reviews, experimental, observational, qualitative designs and
      expert commentaries) describing bridging activities. Grey literature, and
      articles not published in English will be excluded. Two investigators will
      independently complete article selection and data abstraction to minimise bias. A
      data extraction form will be iteratively developed and information from each
      publication will be extracted: (1) bibliographic, (2) methodological, (3)
      demographic, and (4) bridging information. Qualitative content analysis will be
      used to describe key concepts related to bridging. CONCLUSIONS: To our knowledge,
      this will be the first scoping review to describe bridging of ageing and
      disability knowledge, services and policies. The findings will inform the
      development of a taxonomy to define models of bridging that can be implemented
      and further evaluated to enable integrated care and improve systems and services
      for those ageing with disability. ETHICS AND DISSEMINATION: Ethics is not
      required because this is a scoping review of published literature. Findings will
      be disseminated through stakeholder meetings, conference presentations and peer
      reviewed publication.

PMID- 29074512
TI  - Lung function at term in extremely preterm-born infants: a regional prospective
      cohort study.
AB  - OBJECTIVES: To compare lung function of extremely preterm (EP)-born infants with
      and without bronchopulmonary dysplasia (BPD) with that of healthy term-born
      infants, and to determine which perinatal characteristics were associated with
      lung function at term and how predictive these measurements were for later
      respiratory health in EP-born infants. METHODS: Perinatal variables were recorded
      prospectively, and tidal breathing parameters were measured at term-equivalent
      age using electromagnetic inductance plethysmography. Respiratory morbidity was
      defined by hospital readmissions and/or treatment with asthma medications during
      the first year of life. RESULTS: Fifty-two EP-born infants (mean gestational age
      261, range 226-276 weeks) and 45 term-born infants were included. There was
      evidence of significant airway obstruction, higher tidal volumes and increased
      minute ventilation in the EP-born infants with and without BPD, although
      generally more pronounced for those with BPD. Male gender, antenatal steroids and
      number of days on continuous positive airway pressure were associated with lung
      function outcomes at term. A prediction model incorporating two unrelated tidal
      breathing parameters, BPD, birth weight z-score and gender, predicted respiratory
      morbidity in the first year of life with good accuracy (area under the curve
      0.818, sensitivity and specificity 81.8% and 75.0%, respectively). CONCLUSION:
      Lung function measured at term-equivalent age was strikingly abnormal in EP-born
      infants, irrespective of BPD. Tidal breathing parameters may be of value in
      predicting future pulmonary health in infants born premature. TRIAL REGISTRATION
      NUMBER: NCT01150396; Results.

PMID- 29074514
TI  - Projecting diabetes prevalence among Mexicans aged 50 years and older: the Future
      Elderly Model-Mexico (FEM-Mexico).
AB  - OBJECTIVE: Diabetes has been growing as a major health problem and a significant
      burden on the population and on health systems of developing countries like
      Mexico that are also ageing fast. The goal of the study was to estimate the
      future prevalence of diabetes among Mexico's older adults to assess the current
      and future health and economic burden of diabetes. DESIGN: A simulation study
      using longitudinal data from three waves (2001, 2003 and 2012) of the Mexican
      Health and Aging Study and adapting the Future Elderly Model to simulate four
      scenarios of hypothetical interventions that would reduce diabetes incidence and
      to project the future diabetes prevalence rates among populations 50 years and
      older. PARTICIPANTS: Data from 14 662 participants with information on self
      reported diabetes, demographic characteristics, health and mortality. OUTCOME
      MEASURES: We obtained, for each scenario of diabetes incidence reduction, the
      following summary measures for the population aged 50 and older from 2012 to
      2050: prevalence of diabetes, total population with diabetes, number of medical
      visits. RESULTS: In 2012, there were approximately 20.7 million persons aged 50
      and older in Mexico; 19.3% had been diagnosed with diabetes and the 2001-2003
      diabetes incidence was 4.3%. The no-intervention scenario shows that the
      prevalence of diabetes is projected to increase from 19.3% in 2012 to 34.0% in
      2050. Under the 30% incidence reduction scenario, the prevalence of diabetes will
      be 28.6% in 2050. Comparing the no-intervention scenario with the 30% and 60%
      diabetes incidence reduction scenarios, we estimate a total of 816 320 and 1.6
      million annual averted cases of diabetes, respectively, for the year 2020.
      DISCUSSION: Our study underscores the importance of diabetes as a disease by
      itself and also the potential healthcare demands and social burden of this
      disease and the need for policy interventions to reduce diabetes prevalence.

PMID- 29074513
TI  - Study protocol for the 'HelpMeDoIt!' randomised controlled feasibility trial: an
      app, web and social support-based weight loss intervention for adults with
      obesity.
AB  - INTRODUCTION: HelpMeDoIt! will test the feasibility of an innovative weight loss
      intervention using a smartphone app and website. Goal setting, self-monitoring
      and social support are three key facilitators of behaviour change. HelpMeDoIt!
      incorporates these features and encourages participants to invite 'helpers' from
      their social circle to help them achieve their goal(s). AIM: To test the
      feasibility of the intervention in supporting adults with obesity to achieve
      weight loss goals. METHODS AND ANALYSIS: 12-month feasibility randomised
      controlled trial and accompanying process evaluation. Participants (n=120) will
      be adults interested in losing weight, body mass index (BMI)> 30 kg/m2 and
      smartphone users. The intervention group will use the app/website for 12 months.
      Participants will nominate one or more helpers to support them. Helpers have
      access to the app/website. The control group will receive a leaflet on healthy
      lifestyle and will have access to HelpMeDoIt! after follow-up. The key outcome of
      the study is whether prespecified progression criteria have been met in order to
      progress to a larger randomised controlled effectiveness trial. Data will be
      collected at baseline, 6 and 12 months. Outcomes focus on exploring the
      feasibility of delivering the intervention and include: (i) assessing three
      primary outcomes (BMI, physical activity and diet); (ii) secondary outcomes of
      waist/hip circumference, health-related quality of life, social support, self
      efficacy, motivation and mental health; (iii) recruitment and retention; (iv)
      National Health Service (NHS) resource use and participant borne costs; (v)
      usability and acceptability of the app/website; and (vi) qualitative interviews
      with up to 50 participants and 20 helpers on their experiences of the
      intervention. Statistical analyses will focus on feasibility outcomes and provide
      initial estimates of intervention effects. Thematic analysis of qualitative
      interviews will assess implementation, acceptability, mechanisms of effect and
      contextual factors influencing the intervention. ETHICS AND DISSEMINATION: The
      protocol has been approved by the West of Scotland NHS Research Ethics Committee
      (Ref: 15/WS/0288) and the University of Glasgow MVLS College Ethics Committee
      (Ref: 200140108). Findings will be disseminated widely through peer-reviewed
      publication and conference presentations. TRIAL REGISTRATION NUMBER:
      ISRCTN85615983.

PMID- 29074515
TI  - Euthanasia and physician-assisted suicide not meeting due care criteria in the
      Netherlands: a qualitative review of review committee judgements.
AB  - : ObjectivesTo assess how Dutch regional euthanasia review committees (RTE) apply
      the euthanasia and physician-assisted suicide (EAS) due care criteria in cases
      where the criteria are judged not to have been met ('due care not met' (DCNM))
      and to evaluate how the criteria function to set limits in Dutch EAS practice.
      DESIGN: A qualitative review using directed content analysis of DCNM cases in the
      Netherlands from 2012 to 2016 published on the RTE website
      (https://www.euthanasiecommissie.nl/) as of 31 January 2017. RESULTS: Of 33 DCNM
      cases identified (occurring 2012-2016), 32 cases (97%) were published online and
      included in the analysis. 22 cases (69%) violated only procedural criteria,
      relating to improper medication administration or inadequate physician
      consultation. 10 cases (31%) failed to meet substantive criteria, with the most
      common violation involving the no reasonable alternative (to EAS) criterion
      (seven cases). Most substantive cases involved controversial elements, such as
      EAS for psychiatric disorders or 'tired of life', in incapacitated patients or by
      physicians from advocacy organisations. Even in substantive criteria cases, the
      RTE's focus was procedural. The cases were more about unorthodox, unprofessional
      or overconfident physician behaviours and not whether patients should have
      received EAS. However, in some cases, physicians knowingly pushed the limits of
      EAS law. Physicians from euthanasia advocacy organisations were over-represented
      in substantive criteria cases. Trained EAS consultants tended to agree with or
      facilitate EAS in DCNM cases. Physicians and families had difficulty applying
      ambiguous advance directives of incapacitated patients. CONCLUSION: As a
      retrospective review of physician self-reported data, the Dutch RTEs do not focus
      on whether patients should have received EAS, but instead primarily gauge whether
      doctors conducted EAS in a thorough, professional manner. To what extent this
      constitutes enforcement of strict safeguards, especially when cases contain
      controversial features, is not clear.

PMID- 29074517
TI  - How do workplaces, working practices and colleagues affect UK doctors' career
      decisions? A qualitative study of junior doctors' career decision making in the
      UK.
AB  - OBJECTIVES: This study draws on an in-depth investigation of factors that
      influenced the career decisions of junior doctors. SETTING: Junior doctors in the
      UK can choose to enter specialty training (ST) programmes within 2 years of
      becoming doctors. Their specialty choices contribute to shaping the balance of
      the future medical workforce, with views on general practice (GP) careers of
      particular interest because of current recruitment difficulties. This paper
      examines how experiences of medical work and perceptions about specialty training
      shape junior doctors' career decisions. PARTICIPANTS: Twenty doctors in the
      second year of a Foundation Training Programme in England were recruited.
      Purposive sampling was used to achieve a diverse sample from respondents to an
      online survey. RESULTS: Narrative interviewing techniques encouraged doctors to
      reflect on how experiences during medical school and in medical workplaces had
      influenced their preferences and perceptions of different specialties. They also
      spoke about personal aspirations, work priorities and their wider future.Junior
      doctors' decisions were informed by knowledge about the requirements of ST
      programmes and direct observation of the pressures under which ST doctors worked.
      When they encountered negative attitudes towards a specialty they had intended to
      choose, some became defensive while others kept silent. Achievement of an
      acceptable work-life balance was a central objective that could override other
      preferences.Events linked with specific specialties influenced doctors' attitudes
      towards them. For example, findings confirmed that while early, positive
      experiences of GP work could increase its attractiveness, negative experiences in
      GP settings had the opposite effect. CONCLUSIONS: Junior doctors' preferences and
      perceptions about medical work are influenced by multiple intrinsic and extrinsic
      factors and experiences. This paper highlights the importance of understanding
      how perceptions are formed and preferences are developed, as a basis for
      generating learning and working environments that nurture students and motivate
      their professional careers.

PMID- 29074516
TI  - An enquiry based on a standardised questionnaire into knowledge, awareness and
      preferences concerning the care of familial hypercholesterolaemia among primary
      care physicians in the Asia-Pacific region: the "Ten Countries Study".
AB  - OBJECTIVE: To determine physicians' knowledge, awareness and preferences
      regarding the care of familial hypercholesterolaemia (FH) in the Asia-Pacific
      region. SETTING: A formal questionnaire was anonymously completed by physicians
      from different countries/regions in the Asia-Pacific. The survey sought responses
      relating to general familiarity, awareness of management guidelines,
      identification (clinical characteristics and lipid profile), prevalence and
      inheritance, extent of elevation in risk of cardiovascular disease (CVD) and
      practice on screening and treatment. PARTICIPANTS: Practising community
      physicians from Australia, Japan, Malaysia, South Korea, Philippines, Hong Kong,
      China, Vietnam and Taiwan were recruited to complete the questionnaire, with the
      UK as the international benchmark. PRIMARY OUTCOME: An assessment and comparison
      of the knowledge, awareness and preferences of FH among physicians in 10
      different countries/regions. RESULTS: 1078 physicians completed the questionnaire
      from the Asia-Pacific region; only 34% considered themselves to be familiar with
      FH. 72% correctly described FH and 65% identified the typical lipid profile, with
      a higher proportion of physicians from Japan and China selecting the correct FH
      definition and lipid profile compared with those from Vietnam and Philippines.
      However, less than half of the physician were aware of national or international
      management guidelines; this was significantly worse than physicians from the UK
      (35% vs 61%, p<0.001). Knowledge of prevalence (24%), inheritability (41%) and
      CVD risk (9%) of FH were also suboptimal. The majority of the physicians
      considered laboratory interpretative commenting as being useful (81%) and statin
      therapy as an appropriate cholesterol-lowering therapy (89%) for FH management.
      CONCLUSIONS: The study identified important gaps, which are readily addressable,
      in the awareness and knowledge of FH among physicians in the region.
      Implementation of country-specific guidelines and extensive work in FH education
      and awareness programmes are imperative to improve the care of FH in the region.

PMID- 29074520
TI  - Hidden risks your smartphone poses to your career.

PMID- 29074521
TI  - Pharma gifts associated with higher number and cost of prescriptions written.

PMID- 29074518
TI  - Bi-modal stimulation in the treatment of tinnitus: a study protocol for an
      exploratory trial to optimise stimulation parameters and patient subtyping.
AB  - INTRODUCTION: Tinnitus is the perception of sound in the absence of a
      corresponding external acoustic stimulus. Bimodal neuromodulation is emerging as
      a promising treatment for this condition. The main objectives of this study are
      to investigate the relevance of interstimulus timing and the choices of acoustic
      and tongue stimuli for a proprietary bimodal (auditory and somatosensory)
      neuromodulation device, as well as to explore whether specific subtypes of
      patients are differentially responsive to this novel intervention for reducing
      the symptoms of chronic tinnitus. METHODS AND ANALYSIS: This is a two-site,
      randomised, triple-blind, exploratory study of a proprietary neuromodulation
      device with a pre-post and 12-month follow-up design. Three different bimodal
      stimulation parameter sets will be examined. The study will enrol 342 patients,
      split 80:20 between two sites (Dublin, Ireland and Regensburg, Germany), to
      complete 12 weeks of treatment with the device. Patients will be allocated to one
      of three arms using a stepwise stratification according to four binary
      categories: tinnitus tonality, sound level tolerance (using loudness discomfort
      level of <60 dB SL as an indicator for hyperacusis), hearing thresholds and
      presence of a noise-induced audiometric profile. The main indicators of relative
      clinical efficacy for the three different parameter sets are two patient-reported
      outcomes measures, the Tinnitus Handicap Inventory and the Tinnitus Functional
      Index, after 12 weeks of intervention. Clinical efficacy will be further explored
      in a series of patient subtypes, split by the stratification variables and by
      presence of a somatic tinnitus. Evidence for sustained effects on the
      psychological and functional impact of tinnitus will be followed up for 12
      months. Safety data will be collected and reported. A number of feasibility
      measures to inform future trial design include: reasons for exclusion,
      completeness of data collection, attrition rates, patient's adherence to the
      device usage as per manufacturer's instructions and evaluation of alternative
      methods for estimating tinnitus impact and tinnitus loudness. ETHICS AND
      DISSEMINATION: This study protocol is approved by the Tallaght Hospital/St.
      James's Hospital Joint Research Ethics Committee in Dublin, Ireland, and by the
      Ethics Committee of the University Clinic Regensburg, Germany. Findings will be
      disseminated to relevant research, clinical, health service and patient
      communities through publications in peer-reviewed and popular science journals
      and presentations at scientific and clinical conferences. TRIAL REGISTRATION
      NUMBER: The trial is registered on ClinicalTrials.gov (NCT02669069) Pre-results.

PMID- 29074522
TI  - Meet the First Authors.

PMID- 29074519
TI  - Development and pilot testing of a decision aid for the initiation of
      antipsychotic medications in persons with dementia in long-term care using a
      systematic approach: a study protocol.
AB  - INTRODUCTION: Antipsychotic medications are commonly used in long-term care to
      treat neuropsychiatric symptoms of dementia despite concerns that their risks
      (eg, infection, falls, death) may outweigh their benefits. This study protocol
      outlines the development and pilot testing of a decision aid for antipsychotic
      medications that is tailored to the information needs of residents with dementia
      in long-term care and family caregivers (or decision makers). The goals of the
      decision aid are to help residents and caregivers (1) better understand the risks
      and benefits of antipsychotic medications in long-term care, and (2) make
      informed decisions about their use (or non-use). METHODS AND ANALYSIS: This
      multiphased study is being conducted between October 2016 and September 2018. In
      phase I, the decision aid will be developed after consultation with a steering
      group, review of scientific evidence on outcomes associated with pharmacological
      treatments for neuropsychiatric symptoms of dementia in long-term care, review of
      guidelines for the use of antipsychotic medications in long-term care, and review
      of guidelines for writing health information for patients and families. The
      decision aid will also be alpha-tested and redrafted, as necessary, in phase I.
      In phase II, implementation and reporting guidelines for the decision aid will be
      developed in collaboration with Directors of Care in long-term care. In phase
      III, the decision aid will be (1) beta-tested with residents with dementia in
      long-term care and caregivers not involved in the design phase, and (2) assessed
      by an external panel of experts. ETHICS AND DISSEMINATION: Ethical approval for
      this study has been granted by the Research Ethics Board at the University of
      Saskatchewan, approval number Beh 16-465. Findings from this study will be
      disseminated via conference presentations, publications, presentations to policy
      makers and plain language summaries to residents with dementia in long-term care
      and their caregivers.

PMID- 29074523
TI  - PVDOMICS Drive the Pulmonary Hypertension Field Into the Precision Medicine Era.

PMID- 29074525
TI  - Considerations for Cardiac CRISPR.

PMID- 29074524
TI  - Monocyte Recruitment Versus Macrophage Proliferation in Atherosclerosis.

PMID- 29074526
TI  - AMP-Activated Protein Kinase gamma2 to the Rescue in Ischemic Heart.

PMID- 29074527
TI  - Cardiac Cell Therapy Evolving From Complex to Straightforward: Enabling Adoption
      and Affordability.

PMID- 29074528
TI  - CANTOS Trial Validates the Inflammatory Pathogenesis of Atherosclerosis: Setting
      the Stage for a New Chapter in Therapeutic Targeting.

PMID- 29074529
TI  - Researcher, Heal Thyself?

PMID- 29074530
TI  - Elizabeth Murphy: Perseverance Pays Off.

PMID- 29074531
TI  - Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical
      School.

PMID- 29074532
TI  - Identity Crisis for Regenerative Cardiac cKit+ Cells.

PMID- 29074533
TI  - Novel Antithrombotic Drugs on the Horizon: The Ultimate Promise to Prevent
      Clotting While Avoiding Bleeding.

PMID- 29074534
TI  - PVDOMICS: A Multi-Center Study to Improve Understanding of Pulmonary Vascular
      Disease Through Phenomics.

PMID- 29074536
TI  - A Novel Application of Structural Equation Modeling Estimates the Association
      between Oxidative Stress and Colorectal Adenoma.
AB  - In vitro evidence implicates oxidative stress in many adverse health conditions,
      including colorectal neoplasia. In human studies, however, oxidative stress is
      measured by imperfect biomarkers, which are inconsistently associated with health
      outcomes. Structural equation modeling (SEM) offers one possible solution by
      modeling a latent (unobserved) construct from multiple biomarkers. Our goal was
      to investigate the association of a latent oxidative stress variable with
      colorectal adenoma. Using SEM, we analyzed pooled data from two cross-sectional
      studies of colorectal adenoma (n = 526) that measured five plasma biomarkers of
      oxidative stress and inflammation that comprised the latent oxidative stress
      variable: F2-isoprostanes (FIP), fluorescent oxidation products (FOP),
      mitochondrial DNA (MtDNA) copy number, gamma-tocopherol (Gtoc), and C-reactive
      protein (CRP). Higher levels of oxidative stress were associated with colorectal
      adenoma [OR = 3.23 per SD increase in oxidative stress; 95% confidence interval
      (CI), 1.28-8.18]. The latent variable estimate was considerably stronger than the
      associations of adenoma with the individual biomarkers, which were modest and
      mostly nonsignificant. Risk factors were associated with adenoma via the
      oxidative stress pathway, particularly overweight and obesity with an OR = 1.50;
      95% CI, 1.10-2.81; and OR = 2.95; 95% CI, 1.28-12.45, respectively. Oxidative
      stress may be positively associated with colorectal adenoma, and important risk
      factors may act through this mechanism, but the cross-sectional design of the
      current study precludes observing the directionality of associations. The
      presence of an adenoma could affect levels of the circulating biomarkers; thus,
      we should be cautious of strong conclusions until the findings are replicated in
      a follow-up study. Cancer Prev Res; 11(1); 52-58. (c)2017 AACR.

PMID- 29074535
TI  - Flaxseed Consumption Inhibits Chemically Induced Lung Tumorigenesis and Modulates
      Expression of Phase II Enzymes and Inflammatory Cytokines in A/J Mice.
AB  - Flaxseed consumption is associated with reduced oxidative stress and inflammation
      in lung injury models and has shown anticancer effects for breast and prostate
      tissues. However, the chemopreventive potential of flaxseed remains unexplored
      for lung cancer. In this study, we investigated the effect of flaxseed on tobacco
      smoke carcinogen (NNK)-induced lung tumorigenesis in an A/J mouse model. Mice
      exposed to NNK were fed a control diet or a 10% flaxseed-supplemented diet for 26
      weeks. Flaxseed-fed mice showed reduced lung tumor incidence (78%) and
      multiplicity, with an average of 2.7 +/- 2.3 surface lung tumor nodules and 1.0
      +/- 0.9 H&E cross-section nodules per lung compared with the control group, which
      had 100% tumor incidence and an average of 10.2 +/- 5.7 surface lung tumor
      nodules and 3.9 +/- 2.6 H&E cross-section nodules per lung. Furthermore, flaxseed
      fed mice had a lower incidence of adenocarcinomas compared with control-fed mice.
      Western blotting performed on normal lung tissues showed flaxseed suppressed
      phosphorylation (activation) of p-AKT, p-ERK, and p-JNK kinases. RNA-Seq data
      obtained from normal lung and lung tumors of control and flaxseed-fed mice
      suggested that flaxseed intake resulted in differential expression of genes
      involved in inflammation-mediated cytokine signaling (IL1, 6, 8, 9, and 12alpha),
      xenobiotic metabolism (several CYPs, GSTs, and UGTs), and signaling pathways (AKT
      and MAPK) involved in tumor cell proliferation. Together, our results indicate
      that dietary flaxseed supplementation may be an effective chemoprevention
      strategy for chemically induced lung carcinogenesis by altering signaling
      pathways, inflammation, and oxidative stress. Cancer Prev Res; 11(1); 27-37.
      (c)2017 AACR.

PMID- 29074537
TI  - Genetic Variants in Metabolic Signaling Pathways and Their Interaction with
      Lifestyle Factors on Breast Cancer Risk: A Random Survival Forest Analysis.
AB  - Genetic variants in the insulin-like growth factor-I (IGF-I)/insulin resistance
      axis may interact with lifestyle factors, influencing postmenopausal breast
      cancer risk, but these interrelated pathways are not fully understood. In this
      study, we examined 54 single-nucleotide polymorphisms (SNP) in genes related to
      IGF-I/insulin phenotypes and signaling pathways and lifestyle factors in relation
      to postmenopausal breast cancer, using data from 6,567 postmenopausal women in
      the Women's Health Initiative Harmonized and Imputed Genome-Wide Association
      Studies. We used a machine-learning method, two-stage random survival forest
      analysis. We identified three genetic variants (AKT1 rs2494740, AKT1 rs2494744,
      and AKT1 rs2498789) and two lifestyle factors [body mass index (BMI) and dietary
      alcohol intake] as the top five most influential predictors for breast cancer
      risk. The combination of the three SNPs, BMI, and alcohol consumption (>=1 g/day)
      significantly increased the risk of breast cancer in a gene and lifestyle dose
      dependent manner. Our findings provide insight into gene-lifestyle interactions
      and will enable researchers to focus on individuals with risk genotypes to
      promote intervention strategies. These data also suggest potential genetic
      targets in future intervention/clinical trials for cancer prevention in order to
      reduce the risk for breast cancer in postmenopausal women. Cancer Prev Res;
      11(1); 44-51. (c)2017 AACR.

PMID- 29074538
TI  - TGFbeta Promotes Genomic Instability after Loss of RUNX3.
AB  - Studies of genomic instability have historically focused on intrinsic mechanisms
      rather than extrinsic mechanisms based in the tumor microenvironment (TME).
      TGFbeta is the most abundantly secreted cytokine in the TME, where it imparts
      various aggressive characteristics including invasive migration, drug resistance,
      and epithelial-to-mesenchymal transition (EMT). Here we show that TGFbeta also
      promotes genomic instability in the form of DNA double strand breaks (DSB) in
      cancer cells that lack the tumor suppressor gene RUNX3 Loss of RUNX3 resulted in
      transcriptional downregulation of the redox regulator heme oxygenase-1 (HO-1 or
      HMOX1). Consequently, elevated oxidative DNA damage disrupted genomic integrity
      and triggered cellular senescence, which was accompanied by tumor-promoting
      inflammatory cytokine expression and acquisition of the senescence-associated
      secretory phenotype (SASP). Recapitulating the above findings, tumors harboring a
      TGFbeta gene expression signature and RUNX3 loss exhibited higher levels of
      genomic instability. In summary, RUNX3 creates an effective barrier against
      further TGFbeta-dependent tumor progression by preventing genomic instability.
      These data suggest a novel cooperation between cancer cell-extrinsic TGFbeta
      signaling and cancer cell-intrinsic RUNX3 inactivation as aggravating factors for
      genomic instability.Significance: RUNX3 inactivation in cancer removes an
      antioxidant barrier against DNA double strand breaks induced by TGFbeta expressed
      in the tumor microenvironment. Cancer Res; 78(1); 88-102. (c)2017 AACR.

PMID- 29074540
TI  - Traffic-related air pollution exposure over a 5-year period is associated with
      increased risk of asthma and poor lung function in middle age.
AB  - Current evidence concerning the impact of exposure to traffic-related air
      pollution (TRAP) on adult respiratory morbidity mainly comes from cross-sectional
      studies. We sought to establish more robust measures of this association and
      potential gene-environment interactions using longitudinal data from an
      established cohort study.Associations between measures of TRAP (nitrogen dioxide
      (NO2) and distance to major roads) and wheeze, asthma prevalence and lung
      function were investigated in participants of the Tasmanian Longitudinal Health
      Study at 45- and 50-year follow-ups. Generalised estimating equations were used
      to quantify associations and the potential modifying effect of glutathione S
      transferase gene variants.Living <200 m from a major road was associated with
      increased prevalence of current asthma and wheeze, and lower lung function. The
      association between living <200 m from a major road and current asthma and wheeze
      was more marked for carriers of the GSTT1 null and GSTP1 val/val or ile/val
      genotypes. Over the 5-year period, higher NO2 exposures were associated with
      increased current asthma prevalence. Higher NO2 exposure was associated with
      lower forced vital capacity for carriers of the GSTT1 null genotype.TRAP
      exposures were associated with increased risk of asthma, wheeze and lower lung
      function in middle-aged adults. The interaction with the GSTT1 genotype suggests
      that deficient antioxidant mechanisms may play a role in these adverse health
      effects.

PMID- 29074541
TI  - Tuberculosis screening in asylum seekers in Germany, 2015: characteristics of
      cases and yield.

PMID- 29074539
TI  - NFkappaB Promotes Ovarian Tumorigenesis via Classical Pathways That Support
      Proliferative Cancer Cells and Alternative Pathways That Support ALDH+ Cancer
      Stem-like Cells.
AB  - Understanding the mechanisms supporting tumor-initiating cells (TIC) is vital to
      combat advanced-stage recurrent cancers. Here, we show that in advanced ovarian
      cancers NFkappaB signaling via the RelB transcription factor supports TIC
      populations by directly regulating the cancer stem-like associated enzyme
      aldehyde dehydrogenase (ALDH). Loss of RelB significantly inhibited spheroid
      formation, ALDH expression and activity, chemoresistance, and tumorigenesis in
      subcutaneous and intrabursal mouse xenograft models of human ovarian cancer. RelB
      also affected expression of the ALDH gene ALDH1A2 Interestingly, classical
      NFkappaB signaling through the RelA transcription factor was equally important
      for tumorigenesis in the intrabursal model, but had no effect on ALDH. In this
      case, classical signaling via RelA was essential for proliferating cells, whereas
      the alternative signaling pathway was not. Our results show how NFkappaB sustains
      diverse cancer phenotypes via distinct classical and alternative signaling
      pathways, with implications for improved understanding of disease recurrence and
      therapeutic response. Cancer Res; 77(24); 6927-40. (c)2017 AACR.

PMID- 29074542
TI  - RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-alpha and -gamma
      selectivity, suppresses COPD inflammation.
AB  - Novel anti-inflammatory approaches targeting chronically activated kinase
      pathways in chronic obstructive pulmonary disease (COPD) are needed. We evaluated
      RV568, a p38 mitogen-activated protein kinase-alpha and -gamma and SRC family
      kinase inhibitor, in cellular and in vivo models relevant to COPD and examined
      its safety and efficacy in COPD patients.The anti-inflammatory activities of
      RV568 were tested in primary cultured monocytes, macrophages and bronchial
      epithelial cells and in vivo in lipopolysaccharide and cigarette smoke-exposed
      murine models. RV568 was evaluated in a 14-day trial in COPD patients.RV568
      showed potent anti-inflammatory effects in monocytes and macrophages, which were
      often greater than those of corticosteroids or the p38 inhibitor Birb796. RV568
      combined with corticosteroid had anti-inflammatory effects suggestive of a
      synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette
      smoke model. In COPD patients, inhaled RV568 (50 ug and 100 ug) improved pre
      bronchodilator forced expiratory volume in 1 s (69 mL and 48 mL respectively) and
      significantly reduced sputum malondialdehyde (p<0.05) compared to placebo,
      although there were no changes in sputum cell counts. Adverse events during RV568
      and placebo treatment were similar.RV568 shows potent anti-inflammatory effects
      on cell and animal models relevant to COPD. RV568 was well-tolerated and
      demonstrated a modest clinical benefit in a 14-day COPD clinical trial.

PMID- 29074544
TI  - Mycobacterium tuberculosis transmission from patients with drug-resistant
      compared to drug-susceptible TB: a systematic review and meta-analysis.

PMID- 29074546
TI  - Frequency and significance of indeterminate and borderline Quantiferon Gold TB
      IGRA results.

PMID- 29074545
TI  - Idiopathic pulmonary fibrosis: lessons from clinical trials over the past 25
      years.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal
      disease. A major breakthrough in treatment came when, after decades of clinical
      trials which failed to identify an efficacious treatment regimen, two therapies
      were successful in Phase-III trials. The advent of these therapies, nintedanib
      and pirfenidone, meant that for the first time IPF patients had two treatment
      options that could reduce disease progression. This review summarises the key
      lessons to be obtained from the clinical trials that led to the current
      international clinical practice guidelines for the treatment of IPF and provides
      insights for the design of future clinical trials that are needed if we are to
      improve outcomes that are clinically meaningful to IPF patients.

PMID- 29074543
TI  - Association between lung cancer somatic mutations and occupational exposure in
      never-smokers.
AB  - Occupational exposure constitutes a common risk factor for lung cancer. We
      observed molecular alterations in 73% of never-smokers, 35% of men and 8% of
      women were exposed to at least one occupational carcinogen. We report herein
      associations between molecular patterns and occupational exposure.BioCAST was a
      cohort study of lung cancer in never-smokers that reported risk factor exposure
      and molecular patterns. Occupational exposure was assessed via a validated 71
      item questionnaire. Patients were categorised into groups that were unexposed and
      exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel
      exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR,
      KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384
      patients included in BioCAST were analysed. Asbestos-exposed patients displayed a
      significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a
      higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not
      associated with any occupational carcinogens. The DEF-exposed patients were
      diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients
      exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in
      the subgroups, we conclude that occupational exposure slightly affects the
      molecular pattern of lung cancers in never-smokers. In particular, asbestos
      exposed patients have a lower chance of EGFR mutations.

PMID- 29074547
TI  - Large cell neuroendocrine carcinoma of the lung: chemotherapy regimen depends on
      how "large" your diagnostic criteria are.

PMID- 29074548
TI  - Why we should improve current practice of diagnosing and treating pulmonary large
      cell neuroendocrine carcinomas in patients with advanced disease.

PMID- 29074549
TI  - Occupational exposure and asthma control.

PMID- 29074550
TI  - Next generation of anti-inflammatory therapy for COPD?

PMID- 29074551
TI  - The Art of Breathing: Synergy.

PMID- 29074552
TI  - Occupational exposures and mammographic density in Spanish women.
AB  - OBJECTIVES: The association between occupational exposures and mammographic
      density (MD), a marker of breast cancer risk, has not been previously explored.
      Our objective was to investigate the influence of occupational exposure to
      chemical, physical and microbiological agents on MD in adult women. METHODS: This
      is a population-based cross-sectional study based on 1476 female workers aged 45
      65 years from seven Spanish breast cancer screening programmes. Occupational
      history was surveyed by trained staff. Exposure to occupational agents was
      assessed using the Spanish job-exposure matrix MatEmESp. Percentage of MD was
      measured by two radiologists using a semiautomatic computer tool. The association
      was estimated using mixed log-linear regression models adjusting for age,
      education, body mass index, menopausal status, parity, smoking, alcohol intake,
      type of mammography, family history of breast cancer and hormonal therapy use,
      and including screening centre and professional reader as random effects terms.
      RESULTS: Although no association was found with most of the agents, women
      occupationally exposed to perchloroethylene (ebeta=1.51; 95% CI 1.04 to 2.19),
      ionising radiation (ebeta=1.23; 95% CI 0.99 to 1.52) and mould spores
      (ebeta=1.44; 95% CI 1.01 to 2.04) tended to have higher MD. The percentage of
      density increased 12% for every 5 years exposure to perchloroethylene or mould
      spores, 11% for every 5 years exposure to aliphatic/alicyclic hydrocarbon
      solvents and 3% for each 5 years exposure to ionising radiation. CONCLUSIONS:
      Exposure to perchloroethylene, ionising radiation, mould spores or
      aliphatic/alicyclic hydrocarbon solvents in occupational settings could be
      associated with higher MD. Further studies are needed to clarify the accuracy and
      the reasons for these findings.

PMID- 29074553
TI  - Systematic review of universal and targeted workplace interventions for
      depression.
AB  - Depression is increasingly being recognised as a significant mental health
      problem in the workplace contributing to productivity loss and economic burden to
      organisations. This paper reviews recently published randomised controlled trials
      (RCTs) of universal and targeted interventions to reduce depression in the
      workplace. Studies were identified through searches of EMBASE, MEDLINE/PubMed,
      PsycINFO, PsycARTICLES Full Text, and Global Health and Social Policy and
      Practice databases. Studies were included if they included an RCT of a workplace
      intervention for employees targeting depression as the primary outcome. Twenty
      two published RCTs investigating interventions utilising various therapeutic
      approaches were identified. The cognitive behavioural therapy (CBT) approach is
      the most frequently used in the workplace, while interventions that combine
      different therapeutic approaches showed the most promising results. A universal
      intervention in the workplace that combines CBT and coping flexibility recorded
      the highest effect size (d=1.45 at 4 months' follow-up). Most interventions were
      delivered in group format and showed low attrition rates compared with other
      delivery formats. Although all studies reviewed were RCTs, the quality of
      reporting is low. Interventions using different therapeutic approaches with
      different modes of delivery have been used. Most of these interventions were
      shown to reduce depression levels among employees in the workplace, particularly
      those that combine more than one therapeutic approaches.

PMID- 29074554
TI  - Parental occupational exposures and the risk of childhood sporadic
      retinoblastoma: a report from the Children's Oncology Group.
AB  - OBJECTIVES: We examined associations between parental occupational chemical
      exposures up to 10 years before conception and the risk of sporadic
      retinoblastoma among offspring. METHODS: In our multicentre study on non-familial
      retinoblastoma, parents of 187 unilateral and 95 bilateral cases and 155 friend
      controls were interviewed by telephone. Exposure information was collected
      retroactively through a detailed occupational questionnaire that asked fathers to
      report every job held in the 10 years before conception, and mothers 1 month
      before and during the index pregnancy. An industrial hygienist reviewed all
      occupational data and assigned an overall exposure score to each job indicating
      the presence of nine hazardous agents. RESULTS: We estimated elevated ORs for
      unilateral and bilateral retinoblastoma among offspring of fathers who were
      exposed to polycyclic aromatic hydrocarbons or paints in the 10 years before
      conception. However, only for exposure to paints did confidence limits exclude
      the null for bilateral disease (OR: 8.76, 95% CI: 1.32 to 58.09). Maternal
      prenatal exposure to at least one of the nine agents was related to increased
      risk of unilateral disease in their children (OR: 5.25, 95% CI: 1.14 to 24.16).
      Fathers exposed to at least one of the nine agents and who were >=30 years of age
      were at increased risk of having a child diagnosed with bilateral retinoblastoma
      (OR: 6.59, 95% CI: 1.34 to 32.42). CONCLUSIONS: Our results suggest a role for
      several hazardous occupational exposures in the development of childhood
      retinoblastoma.

PMID- 29074555
TI  - Efficient Prioritization of Multiple Causal eQTL Variants via Sparse Polygenic
      Modeling.
AB  - Expression quantitative trait loci (eQTL) studies have typically used single
      variant association analysis to identify genetic variants correlated with gene
      expression. However, this approach has several drawbacks: causal variants cannot
      be distinguished from nonfunctional variants in strong linkage disequilibrium,
      combined effects from multiple causal variants cannot be captured, and low
      frequency (<5% MAF) eQTL variants are difficult to identify. While these issues
      possibly could be overcome by using sparse polygenic models, which associate
      multiple genetic variants with gene expression simultaneously, the predictive
      performance of these models for eQTL studies has not been evaluated. Here, we
      assessed the ability of three sparse polygenic models (Lasso, Elastic Net, and
      BSLMM) to identify causal variants, and compared their efficacy to single-variant
      association analysis and a fine-mapping model. Using simulated data, we
      determined that, while these methods performed similarly when there was one
      causal SNP present at a gene, BSLMM substantially outperformed single-variant
      association analysis for prioritizing causal eQTL variants when multiple causal
      eQTL variants were present (1.6- to 5.2-fold higher recall at 20% precision), and
      identified up to 2.3-fold more low frequency variants as the top eQTL SNP.
      Analysis of real RNA-seq and whole-genome sequencing data of 131 iPSC samples
      showed that the eQTL SNPs identified by BSLMM had a higher functional enrichment
      in DHS sites and were more often low-frequency than those identified with single
      variant association analysis. Our study showed that BSLMM is a more effective
      approach than single-variant association analysis for prioritizing multiple
      causal eQTL variants at a single gene.

PMID- 29074556
TI  - Apolipoprotein E polymorphisms are associated with ischemic stroke susceptibility
      in a Northwest China Han population.
AB  - Ischemic stroke (IS), the leading neurology cause of death and disability
      worldwide, is influenced by gene polymorphisms. To explore the association
      between IS and Apolipoprotein E (APOE) gene polymorphisms, a case-control study
      containing 513 IS patients and 514 controls without IS was conducted in a
      Northwest China Han population. MassARRAY iPLEX system was applied to determine
      the APOE polymorphisms according to the alleles of two single nucleotide
      polymorphisms (SNPs) of APOE, rs429358, and rs7412. The results showed that
      rs429358 and rs7412 were in Hardy-Weinberg equilibrium (HWE) in both cases and
      controls groups. APOE epsilon4 allele, epsilon4/epsilon4 genotype, and epsilon4
      containing genotypes were associated with IS. According to the results of Trial
      of ORG 10172 in Acute Stroke Treatment (TOAST) classification system, APOE
      epsilon2 allele, epsilon4 allele, and epsilon4/epsilon4 genotype were associated
      with large artery atherosclerosis IS subtypes. In addition, the results also
      indicated that the epsilon4 allele related to undetermined IS and
      epsilon4/epsilon4 genotype was related to small vessel disease IS. Compared with
      subjects with non-epsilon4-containing genotypes, the total cholesterol (TC) and
      low-density lipoprotein (LDL) level in blood and the proportion of cardiopath
      history were higher in all subjects with epsilon4-containing genotypes. Besides,
      the triacylglycerides (TG) level in blood was higher in controls with epsilon4
      containing genotypes. In conclusion, in a Northwest China Han population, APOE
      epsilon4 allele was associated with blood lipid level. The TC and LDL levels were
      the independent risk factors for IS. APOE was a risk gene for IS, but not
      independent, especially for large artery atherosclerosis IS.

PMID- 29074558
TI  - miR-6743-5p, as a direct upstream regulator of GRIM-19, enhances proliferation
      and suppresses apoptosis in glioma cells.
AB  - Gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) has been
      recognized as a tumor suppressor protein, which regulates cell growth, apoptosis,
      and migration by signal transducer and activator of transcription 3 (STAT3)
      signaling pathway and non-STAT3 pathway in glioma cells. Here, we investigated
      the molecular mechanisms that regulated GRIM-19 expression in glioma cells. By
      the TargetScan algorithm, four miRNAs, hsa-miR-17-3p, hsa-miR-423-5p, hsa-miR
      3184-5p, and hsa-miR-6743-5p, were identified with the potential to bind with 3'
      UTR of GRIM-19. Further miRNA inhibitor transfection and luciferase assays
      revealed that miR-6743-5p was able to directly target the 3'-UTR of GRIM-19.
      Additionally, miR-6743-5p expression was inversely related with GRIM-19
      expression in glioma specimens and cell lines. Moreover, the inhibition of miR
      6743-5p caused a significant inhibition of cell proliferation and a marked
      promotion of cell apoptosis in glioma cells, and this phenotype was rescued by
      GRIM-19 knockdown. Finally, the inhibition of miR-6743-5p expression suppressed
      the phosphorylation of STAT3, and the mRNA expression of CyclinD1 and Bcl-2, two
      target genes of STAT3, while miR-6743-5p mimic had the inversed effects.
      Treatment with STAT3 inhibitor AG490 partially rescued the proliferation
      promoting and anti-apoptosis effects of miR-6743-5p overexpression or GRIM-19
      knockdown. Collectively, miR-6743-5p may act as an oncomiRNA in glioma by
      targetting GRIM-19 and STAT3.

PMID- 29074559
TI  - Resveratrol increases nucleus pulposus matrix synthesis through activating the
      PI3K/Akt signaling pathway under mechanical compression in a disc organ culture.
AB  - Disc nucleus pulposus (NP) matrix homeostasis is important for normal disc
      function. Mechanical overloading seriously decreases matrix synthesis and
      increases matrix degradation. The present study aims to investigate the effects
      of resveratrol on disc NP matrix homeostasis under a relatively high-magnitude
      mechanical compression and the potential mechanism underlying this process.
      Porcine discs were perfusion-cultured and subjected to a relatively high
      magnitude mechanical compression (1.3 MPa at a frequency of 1.0 Hz for 2 h once
      per day) for 7 days in a mechanically active bioreactor. The non-compressed discs
      were used as controls. Resveratrol was added along with culture medium to observe
      the effects of resveratrol on NP matrix synthesis under mechanical load
      respectively. NP matrix synthesis was evaluated by histology, biochemical content
      (glycosaminoglycan (GAG) and hydroxyproline (HYP)), and expression of matrix
      macromolecules (aggrecan and collagen II). Results showed that this high
      magnitude mechanical compression significantly decreased NP matrix content,
      indicated by the decreased staining intensity of Alcian Blue and biochemical
      content (GAG and HYP), and the down-regulated expression of NP matrix
      macromolecules (aggrecan and collagen II). Further analysis indicated that
      resveratrol partly stimulated NP matrix synthesis and increased activity of the
      PI3K/Akt pathway in a dose-dependent manner under mechanical compression.
      Together, resveratrol is beneficial for disc NP matrix synthesis under mechanical
      overloading, and the activation of the PI3K/Akt pathway may participate in this
      regulatory process. Resveratrol may be promising to regenerate mechanical
      overloading-induced disc degeneration.

PMID- 29074557
TI  - Roles of miRNAs and long noncoding RNAs in the progression of diabetic
      retinopathy.
AB  - Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults
      across the world. The pathogenesis of DR is multifactorial and the molecular
      mechanisms are still not fully understood. Accumulating evidence has demonstrated
      that noncoding RNAs (ncRNAs) may be aberrantly expressed and may play vital roles
      in the development of DR. Amongst ncRNAs, miRNAs and long ncRNAs (lncRNAs) are
      known for their regulatory functions. Here, we summarize the functions and
      mechanisms of known aberrantly expressed miRNAs and lncRNAs in DR. Additionally,
      a novel lncRNA-mRNA-miRNA network is included in this review. We highlight
      original studies that provide detailed data about the mechanisms of miRNAs and
      lncRNAs, their applications as diagnostic or prognostic biomarkers, and their
      potential therapeutic targets. In conclusion, this review will help us gain a
      better understanding of the molecular mechanisms by which miRNAs and lncRNAs
      perform their functions in DR, and provide general strategies and directions for
      future research.

PMID- 29074561
TI  - Assessment of the incorporation of CNV surveillance into gene panel next
      generation sequencing testing for inherited retinal diseases.
AB  - BACKGROUND: Diagnostic use of gene panel next-generation sequencing (NGS)
      techniques is commonplace for individuals with inherited retinal dystrophies
      (IRDs), a highly genetically heterogeneous group of disorders. However, these
      techniques have often failed to capture the complete spectrum of genomic
      variation causing IRD, including CNVs. This study assessed the applicability of
      introducing CNV surveillance into first-tier diagnostic gene panel NGS services
      for IRD. METHODS: Three read-depth algorithms were applied to gene panel NGS data
      sets for 550 referred individuals, and informatics strategies used for quality
      assurance and CNV filtering. CNV events were confirmed and reported to referring
      clinicians through an accredited diagnostic laboratory. RESULTS: We confirmed the
      presence of 33 deletions and 11 duplications, determining these findings to
      contribute to the confirmed or provisional molecular diagnosis of IRD for 25
      individuals. We show that at least 7% of individuals referred for diagnostic
      testing for IRD have a CNV within genes relevant to their clinical diagnosis, and
      determined a positive predictive value of 79% for the employed CNV filtering
      techniques. CONCLUSION: Incorporation of CNV analysis increases diagnostic yield
      of gene panel NGS diagnostic tests for IRD, increases clarity in diagnostic
      reporting and expands the spectrum of known disease-causing mutations.

PMID- 29074562
TI  - Expanding the clinical spectrum of recessive truncating mutations of KLHL7 to a
      Bohring-Opitz-like phenotype.
AB  - BACKGROUND: Bohring-Opitz syndrome (BOS) is a rare genetic disorder characterised
      by a recognisable craniofacial appearance and a typical 'BOS' posture. BOS is
      caused by sporadic mutations ofASXL1. However, several typical patients with BOS
      have no molecular diagnosis, suggesting clinical and genetic heterogeneity.
      OBJECTIVES: To expand the phenotypical spectrum of autosomal recessive variants
      of KLHL7, reported as causing Crisponi syndrome/cold-induced sweating syndrome
      type 1 (CS/CISS1)-like syndrome. METHODS: We performed whole-exome sequencing in
      two families with a suspected recessive mode of inheritance. We used the
      Matchmaker Exchange initiative to identify additional patients. RESULTS: Here, we
      report six patients with microcephaly, facial dysmorphism, including
      exophthalmos, nevus flammeus of the glabella and joint contractures with a
      suspected BOS posture in five out of six patients. We identified autosomal
      recessive truncating mutations in the KLHL7 gene. KLHL7 encodes a BTB-kelch
      protein implicated in the cell cycle and in protein degradation by the ubiquitin
      proteasome pathway. Recently, biallelic mutations in the KLHL7 gene were reported
      in four families and associated with CS/CISS1, characterised by clinical features
      overlapping with our patients. CONCLUSION: We have expanded the clinical spectrum
      of KLHL7 autosomal recessive variants by describing a syndrome with features
      overlapping CS/CISS1 and BOS.

PMID- 29074560
TI  - A network meta-analysis of short-term efficacy of different single-drug targeted
      therapies in the treatment of renal cell carcinoma.
AB  - The network meta-analysis was conducted to compare the short-term efficacy of
      different single-drug targeted therapies in the treatment of renal cell carcinoma
      (RCC). We initially searched databases for randomized controlled trials (RCTs) on
      different single-drug targeted therapies in treating RCC. The meta-analysis
      combined the direct and indirect evidence to calculate the pooled odds ratios
      (OR) and draw surface under the cumulative ranking curves (SUCRA). A total of 14
      eligible RCTs were ultimately selected. The partial response (PR) of Cabozantinib
      in the treatment of RCC was better than Sunitinib (OR = 2.7, 95%CI = 1.0-7.8),
      Everolimus (OR = 8.1, 95%CI = 3.1-25.0), and Temsirolimus (OR = 4.8, 95%CI = 1.0
      31.0); the overall response rate (ORR) of Cabozantinib was better than Sorafenib,
      Sunitinib, Everolimus, and Temsirolimus (OR = 5.5, 95%CI = 1.1-27.0; OR = 2.6,
      95%CI = 1.1-6.6; OR = 8.3, 95%CI = 3.5-20.0; OR = 5.7, 95%CI = 1.3-28.0
      respectively). In addition, as for complete response (CR), PR, stable disease
      (SD), progressive disease (PD), ORR, and disease control rate (DCR), Cabozantinib
      had the best short-term efficacy among nine single-drug targeted therapies in the
      treatment of RCC (CR: 50.3%; PR: 93.6%; SD: 75.1%; PD: 68.0%; ORR: 95.5%; DCR:
      73.2%); while Everolimus had the worst short-term efficacy (CR: 33.6%; PR: 22.3%;
      SD: 78.0%; PD: 35.9%; ORR: 22.9%; DCR: 19.9%). Our network meta-analysis
      indicated that Cabozantinib might have better short-term efficacy than other
      regimens in the treatment of RCC, while Everolimus might have poor short-term
      efficacy.

PMID- 29074563
TI  - Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic
      review and bayesian meta-analysis.
AB  - Objective To provide evidence to support updated guidelines for the management of
      pregnant women with hereditary thrombophilia in order to reduce the risk of a
      first venous thromboembolism (VTE) in pregnancy.Design Systematic review and
      bayesian meta-analysis.Data sources Embase, Medline, Web of Science, Cochrane
      Library, and Google Scholar from inception through 14 November 2016.Review
      methods Observational studies that reported on pregnancies without the use of
      anticoagulants and the outcome of first VTE for women with thrombophilia were
      eligible for inclusion. VTE was considered established if it was confirmed by
      objective means, or when the patient had received a full course of a full dose
      anticoagulant treatment without objective testing. Results 36 studies were
      included in the meta-analysis. All thrombophilias increased the risk for
      pregnancy associated VTE (probabilities >=91%). Regarding absolute risks of
      pregnancy associated VTE, high risk thrombophilias were antithrombin deficiency
      (antepartum: 7.3%, 95% credible interval 1.8% to 15.6%; post partum: 11.1%, 3.7%
      to 21.0%), protein C deficiency (antepartum: 3.2%, 0.6% to 8.2%; post partum:
      5.4%, 0.9% to 13.8%), protein S deficiency (antepartum: 0.9%, 0.0% to 3.7%; post
      partum: 4.2%; 0.7% to 9.4%), and homozygous factor V Leiden (antepartum: 2.8%,
      0.0% to 8.6%; post partum: 2.8%, 0.0% to 8.8%). Absolute combined antepartum and
      postpartum risks for women with heterozygous factor V Leiden, heterozygous
      prothrombin G20210A mutations, or compound heterozygous factor V Leiden and
      prothrombin G20210A mutations were all below 3%. Conclusions Women with
      antithrombin, protein C, or protein S deficiency or with homozygous factor V
      Leiden should be considered for antepartum or postpartum thrombosis prophylaxis,
      or both. Women with heterozygous factor V Leiden, heterozygous prothrombin
      G20210A mutation, or compound heterozygous factor V Leiden and prothrombin
      G20210A mutation should generally not be prescribed thrombosis prophylaxis on the
      basis of thrombophilia and family history alone. These data should be considered
      in future guidelines on pregnancy associated VTE risk.

PMID- 29074564
TI  - HID-1 controls formation of large dense core vesicles by influencing cargo
      sorting and trans-Golgi network acidification.
AB  - Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides
      and peptide hormones. They form at the trans-Golgi network (TGN), where their
      soluble content aggregates to form a dense core, but the mechanisms controlling
      biogenesis are still not completely understood. Recent studies have implicated
      the peripheral membrane protein HID-1 in neuropeptide sorting and insulin
      secretion. Using CRISPR/Cas9, we generated HID-1 KO rat neuroendocrine cells, and
      we show that the absence of HID-1 results in specific defects in peptide hormone
      and monoamine storage and regulated secretion. Loss of HID-1 causes a reduction
      in the number of LDCVs and affects their morphology and biochemical properties,
      due to impaired cargo sorting and dense core formation. HID-1 KO cells also
      exhibit defects in TGN acidification together with mislocalization of the Golgi
      enriched vacuolar H+-ATPase subunit isoform a2. We propose that HID-1 influences
      early steps in LDCV formation by controlling dense core formation at the TGN.

PMID- 29074565
TI  - Fine-tuning the orientation of the polarity axis by Rga1, a Cdc42 GTPase
      activating protein.
AB  - In yeast and animal cells, signaling pathways involving small guanosine
      triphosphatases (GTPases) regulate cell polarization. In budding yeast, selection
      of a bud site directs polarity establishment and subsequently determines the
      plane of cell division. Rga1, a Cdc42 GTPase-activating protein, prevents budding
      within the division site by inhibiting Cdc42 repolarization. A protein complex
      including Nba1 and Nis1 is involved in preventing rebudding at old division
      sites, yet how these proteins and Rga1 might function in negative polarity
      signaling has been elusive. Here we show that Rga1 transiently localizes to the
      immediately preceding and older division sites by interacting with Nba1 and Nis1.
      The LIM domains of Rga1 are necessary for its interaction with Nba1, and loss of
      this interaction results in premature delocalization of Rga1 from the immediately
      preceding division site and, consequently, abnormal bud-site selection in
      daughter cells. However, such defects are minor in mother cells of these mutants,
      likely because the G1 phase is shorter and a new bud site is established prior to
      delocalization of Rga1. Indeed, our biphasic mathematical model of Cdc42
      polarization predicts that premature delocalization of Rga1 leads to more
      frequent Cdc42 repolarization within the division site when the first temporal
      step in G1 is assumed to last longer. Spatial distribution of a Cdc42 GAP in
      coordination with G1 progression may thus be critical for fine-tuning the
      orientation of the polarity axis in yeast.

PMID- 29074569
TI  - Commentaries on Viewpoint: Loopomics: a new functional approach to life.

PMID- 29074570
TI  - Last Word on Viewpoint: Loopomics: a new functional approach to life.

PMID- 29074566
TI  - Actomyosin contractility regulators stabilize the cytoplasmic bridge between the
      two primordial germ cells during Caenorhabditis elegans embryogenesis.
AB  - Stable cytoplasmic bridges arise from failed cytokinesis, the last step of cell
      division, and are a key feature of syncytial architectures in the germline of
      most metazoans. Whereas the Caenorhabditiselegans germline is syncytial, its
      formation remains poorly understood. We found that the germline precursor
      blastomere, P4 , fails cytokinesis, leaving a stable cytoplasmic bridge between
      the two daughter cells, Z2 and Z3 Depletion of several regulators of actomyosin
      contractility resulted in a regression of the membrane partition between Z2 and
      Z3, indicating that they are required to stabilize the cytoplasmic bridge.
      Epistatic analysis revealed a pathway in which Rho regulators promote
      accumulation of the noncannonical anillin ANI-2 at the stable cytoplasmic bridge,
      which in turns promotes the accumulation of the nonmuscle myosin II NMY-2 and the
      midbody component CYK-7 at the bridge, in part by limiting the accumulation of
      canonical anillin ANI-1. Our results uncover key steps in C. elegans germline
      formation and define a set of conserved regulators that are enriched at the
      primordial germ cell cytoplasmic bridge to ensure its stability during embryonic
      development.

PMID- 29074568
TI  - Sendai virus recruits cellular villin to remodel actin cytoskeleton during fusion
      with hepatocytes.
AB  - Reconstituted Sendai viral envelopes (virosomes) are well recognized for their
      promising potential in membrane fusion-mediated delivery of bioactive molecules
      to liver cells. Despite the known function of viral envelope glycoproteins in
      catalyzing fusion with cellular membrane, the role of host cell proteins remains
      elusive. Here, we used two-dimensional differential in-gel electrophoresis to
      analyze hepatic cells in early response to virosome-induced membrane fusion.
      Quantitative mass spectrometry together with biochemical analysis revealed that
      villin, an actin-modifying protein, is differentially up-regulated and
      phosphorylated at threonine 206-an early molecular event during membrane fusion.
      We found that villin influences actin dynamics and that this influence, in turn,
      promotes membrane mixing through active participation of Sendai viral envelope
      glycoproteins. Modulation of villin in host cells also resulted in a discernible
      effect on the entry and egress of progeny Sendai virus. Taken together, these
      results suggest a novel mechanism of regulated viral entry in animal cells
      mediated by host factor villin.

PMID- 29074571
TI  - Measurement of Vo2max in clinical groups is feasible and necessary.

PMID- 29074572
TI  - Interpreting the averaging methods to estimate oxygen uptake kinetics parameters.

PMID- 29074567
TI  - Image-based drug screen identifies HDAC inhibitors as novel Golgi disruptors
      synergizing with JQ1.
AB  - The Golgi apparatus is increasingly recognized as a major hub for cellular
      signaling and is involved in numerous pathologies, including neurodegenerative
      diseases and cancer. The study of Golgi stress-induced signaling pathways relies
      on the selectivity of the available tool compounds of which currently only a few
      are known. To discover novel Golgi-fragmenting agents, transcriptomic profiles of
      cells treated with brefeldin A, golgicide A, or monensin were generated and
      compared with a database of gene expression profiles from cells treated with
      other bioactive small molecules. In parallel, a phenotypic screen was performed
      for compounds that alter normal Golgi structure. Histone deacetylase (HDAC)
      inhibitors and DNA-damaging agents were identified as novel Golgi disruptors.
      Further analysis identified HDAC1/HDAC9 as well as BRD8 and DNA-PK as important
      regulators of Golgi breakdown mediated by HDAC inhibition. We provide evidence
      that combinatorial HDACi/(+)-JQ1 treatment spurs synergistic Golgi dispersal in
      several cancer cell lines, pinpointing a possible link between drug-induced
      toxicity and Golgi morphology alterations.

PMID- 29074573
TI  - Reply to Francescato et al.: Interpreting the averaging methods to estimate
      oxygen uptake kinetics parameters.

PMID- 29074574
TI  - Rheumatoid arthritis, gammadelta T cells and bisphosphonates.

PMID- 29074575
TI  - Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires
      Large-Scale Perturbation of the Inhibitory Population.
AB  - Neurons within cortical microcircuits are interconnected with recurrent
      excitatory synaptic connections that are thought to amplify signals (Douglas and
      Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature
      discrimination. Strong inhibition (Haider et al., 2013) counterbalances
      excitation, enabling sensory features to be sharpened and represented by sparse
      codes (Willmore et al., 2011). This balance between excitation and inhibition
      makes it difficult to assess the strength, or gain, of recurrent excitatory
      connections within cortical networks, which is key to understanding their
      operational regime and the computations that they perform. Networks that combine
      an unstable high-gain excitatory population with stabilizing inhibitory feedback
      are known as inhibition-stabilized networks (ISNs) (Tsodyks et al., 1997).
      Theoretical studies using reduced network models predict that ISNs produce
      paradoxical responses to perturbation, but experimental perturbations failed to
      find evidence for ISNs in cortex (Atallah et al., 2012). Here, we reexamined this
      question by investigating how cortical network models consisting of many neurons
      behave after perturbations and found that results obtained from reduced network
      models fail to predict responses to perturbations in more realistic networks. Our
      models predict that a large proportion of the inhibitory network must be
      perturbed to reliably detect an ISN regime robustly in cortex. We propose that
      wide-field optogenetic suppression of inhibition under promoters targeting a
      large fraction of inhibitory neurons may provide a perturbation of sufficient
      strength to reveal the operating regime of cortex. Our results suggest that
      detailed computational models of optogenetic perturbations are necessary to
      interpret the results of experimental paradigms.SIGNIFICANCE STATEMENT Many
      useful computational mechanisms proposed for cortex require local excitatory
      recurrence to be very strong, such that local inhibitory feedback is necessary to
      avoid epileptiform runaway activity (an "inhibition-stabilized network" or "ISN"
      regime). However, recent experimental results suggest that this regime may not
      exist in cortex. We simulated activity perturbations in cortical networks of
      increasing realism and found that, to detect ISN-like properties in cortex, large
      proportions of the inhibitory population must be perturbed. Current experimental
      methods for inhibitory perturbation are unlikely to satisfy this requirement,
      implying that existing experimental observations are inconclusive about the
      computational regime of cortex. Our results suggest that new experimental designs
      targeting a majority of inhibitory neurons may be able to resolve this question.

PMID- 29074576
TI  - A Presynaptic Function of Shank Protein in Drosophila.
AB  - Human genetic studies support that loss-of-function mutations in the SH3 domain
      and ankyrin repeat containing family proteins (SHANK1-3), the large synaptic
      scaffolding proteins enriched at the postsynaptic density of excitatory synapses,
      are causative for autism spectrum disorder and other neuropsychiatric disorders
      in humans. To better understand the in vivo functions of Shank and facilitate
      dissection of neuropathology associated with SHANK mutations in human, we
      generated multiple mutations in the Shank gene, the only member of the SHANK
      family in Drosophila melanogaster Both male and female Shank null mutants were
      fully viable and fertile with no apparent morphological or developmental defects.
      Expression analysis revealed apparent enrichment of Shank in the neuropils of the
      CNS. Specifically, Shank coexpressed with another PSD scaffold protein, Homer, in
      the calyx of mushroom bodies in the brain. Consistent with high expression in
      mushroom body calyces, Shank mutants show an abnormal calyx structure and reduced
      olfactory acuity. These morphological and functional phenotypes were fully
      rescued by pan-neuronal reexpression of Shank, and only partially rescued by
      presynaptic but no rescue by postsynaptic reexpression of Shank. Our findings
      thus establish a previously unappreciated presynaptic function of
      Shank.SIGNIFICANCE STATEMENT Mutations in SHANK family genes are causative for
      idiopathic autism spectrum disorder. To understand the neural function of Shank,
      a large scaffolding protein enriched at the postsynaptic densities, we examined
      the role of Drosophila Shank in synapse development at the peripheral
      neuromuscular junctions and the central mushroom body calyx. Our results
      demonstrate that, in addition to its conventional postsynaptic function, Shank
      also acts presynaptically in synapse development in the brain. This study offers
      novel insights into the synaptic role of Shank.

PMID- 29074577
TI  - Functional analyses of the CIF1-CIF2 complex in trypanosomes identify the
      structural motifs required for cytokinesis.
AB  - Cytokinesis in trypanosomes occurs uni-directionally along the longitudinal axis
      from the cell anterior towards the cell posterior and requires a trypanosome
      specific CIF1-CIF2 protein complex. However, little is known about the
      contribution of the structural motifs in CIF1 and CIF2 to complex assembly and
      cytokinesis. Here, we demonstrate that the two zinc-finger motifs but not the
      coiled-coil motif in CIF1 are required for interaction with the EF-hand motifs in
      CIF2. We further show that localization of CIF1 depends on the coiled-coil motif
      and the first zinc-finger motif and that localization of CIF2 depends on the EF
      hand motifs. Deletion of the coiled-coil motif and mutation of either zinc-finger
      motif in CIF1 disrupts cytokinesis. Furthermore, mutation of either zinc-finger
      motif in CIF1 mislocalizes CIF2 to the cytosol and destabilizes CIF2, whereas
      deletion of the coiled-coil motif in CIF1 spreads CIF2 over to the new flagellum
      attachment zone and stabilizes CIF2. Together, these results uncover the
      requirement of the coiled-coil and zinc-finger motifs for CIF1 function in
      cytokinesis and for CIF2 localization and stability, providing structural
      insights into the functional interplay between the two cytokinesis regulators.

PMID- 29074579
TI  - Phragmoplast microtubule dynamics - a game of zones.
AB  - Plant morphogenesis relies on the accurate positioning of the partition (cell
      plate) between dividing cells during cytokinesis. The cell plate is synthetized
      by a specialized structure called the phragmoplast, which consists of
      microtubules, actin filaments, membrane compartments and associated proteins. The
      phragmoplast forms between daughter nuclei during the transition from anaphase to
      telophase. As cells are commonly larger than the originally formed phragmoplast,
      the construction of the cell plate requires phragmoplast expansion. This
      expansion depends on microtubule polymerization at the phragmoplast forefront
      (leading zone) and loss at the back (lagging zone). Leading and lagging zones
      sandwich the 'transition' zone. A population of stable microtubules in the
      transition zone facilitates transport of building materials to the midzone where
      the cell plate assembly takes place. Whereas microtubules undergo dynamic
      instability in all zones, the overall balance appears to be shifted towards
      depolymerization in the lagging zone. Polymerization of microtubules behind the
      lagging zone has not been reported to date, suggesting that microtubule loss
      there is irreversible. In this Review, we discuss: (1) the regulation of
      microtubule dynamics in the phragmoplast zones during expansion; (2) mechanisms
      of the midzone establishment and initiation of cell plate biogenesis; and (3)
      signaling in the phragmoplast.

PMID- 29074578
TI  - Dynein and EFF-1 control dendrite morphology by regulating the localization
      pattern of SAX-7 in epidermal cells.
AB  - Our previous work showed that the cell adhesion molecule SAX-7 forms an elaborate
      pattern in Caenorhabditis elegans epidermal cells, which instructs PVD dendrite
      branching. However, the molecular mechanism forming the SAX-7 pattern in the
      epidermis is not fully understood. Here, we report that the dynein light
      intermediate chain DLI-1 and the fusogen EFF-1 are required in epidermal cells to
      pattern SAX-7. While previous reports suggest that these two molecules act cell
      autonomously in the PVD, our results show that the disorganized PVD dendritic
      arbors in these mutants are due to the abnormal SAX-7 localization patterns in
      epidermal cells. Three lines of evidence support this notion. First, the
      epidermal SAX-7 pattern was severely affected in dli-1 and eff-1 mutants. Second,
      the abnormal SAX-7 pattern was predictive of the ectopic PVD dendrites. Third,
      expression of DLI-1 or EFF-1 in the epidermis rescued both the SAX-7 pattern and
      the disorganized PVD dendrite phenotypes, whereas expression of these molecules
      in the PVD did not. We also show that DLI-1 functions cell-autonomously in the
      PVD to promote distal branch formation. These results demonstrate the unexpected
      roles of DLI-1 and EFF-1 in the epidermis in the control of PVD dendrite
      morphogenesis.

PMID- 29074580
TI  - An interferon-independent lncRNA promotes viral replication by modulating
      cellular metabolism.
AB  - Viruses regulate host metabolic networks to improve their survival. The molecules
      that are responsive to viral infection and regulate such metabolic changes are
      hardly known, but are essential for understanding viral infection. Here we
      identify a long noncoding RNA (lncRNA) that is induced by multiple viruses, but
      not by type I interferon (IFN-I), and facilitates viral replication in mouse and
      human cells. In vivo deficiency of lncRNA-ACOD1 (a lncRNA identified by its
      nearest coding gene Acod1, aconitate decarboxylase 1) significantly attenuates
      viral infection through IFN-I-IRF3 (interferon regulatory factor 3)-independent
      pathways. Cytoplasmic lncRNA-ACOD1 directly binds the metabolic enzyme glutamic
      oxaloacetic transaminase (GOT2) near the substrate niche, enhancing its catalytic
      activity. Recombinant GOT2 protein and its metabolites could rescue viral
      replication upon lncRNA-ACOD1 deficiency and increase lethality. This work
      reveals a feedback mechanism of virus-induced lncRNA-mediated metabolic promotion
      of viral infection and a potential target for developing broad-acting antiviral
      therapeutics.

PMID- 29074582
TI  - A generative vision model that trains with high data efficiency and breaks text
      based CAPTCHAs.
AB  - Learning from a few examples and generalizing to markedly different situations
      are capabilities of human visual intelligence that are yet to be matched by
      leading machine learning models. By drawing inspiration from systems
      neuroscience, we introduce a probabilistic generative model for vision in which
      message-passing-based inference handles recognition, segmentation, and reasoning
      in a unified way. The model demonstrates excellent generalization and occlusion
      reasoning capabilities and outperforms deep neural networks on a challenging
      scene text recognition benchmark while being 300-fold more data efficient. In
      addition, the model fundamentally breaks the defense of modern text-based
      CAPTCHAs (Completely Automated Public Turing test to tell Computers and Humans
      Apart) by generatively segmenting characters without CAPTCHA-specific heuristics.
      Our model emphasizes aspects such as data efficiency and compositionality that
      may be important in the path toward general artificial intelligence.

PMID- 29074581
TI  - Atomic model for the dimeric FO region of mitochondrial ATP synthase.
AB  - Mitochondrial adenosine triphosphate (ATP) synthase produces the majority of ATP
      in eukaryotic cells, and its dimerization is necessary to create the inner
      membrane folds, or cristae, characteristic of mitochondria. Proton translocation
      through the membrane-embedded FO region turns the rotor that drives ATP synthesis
      in the soluble F1 region. Although crystal structures of the F1 region have
      illustrated how this rotation leads to ATP synthesis, understanding how proton
      translocation produces the rotation has been impeded by the lack of an
      experimental atomic model for the FO region. Using cryo-electron microscopy, we
      determined the structure of the dimeric FO complex from Saccharomyces cerevisiae
      at a resolution of 3.6 angstroms. The structure clarifies how the protons travel
      through the complex, how the complex dimerizes, and how the dimers bend the
      membrane to produce cristae.

PMID- 29074583
TI  - Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino
      acid efflux from lysosomes.
AB  - The lysosome degrades and recycles macromolecules, signals to the cytosol and
      nucleus, and is implicated in many diseases. Here, we describe a method for the
      rapid isolation of mammalian lysosomes and use it to quantitatively profile
      lysosomal metabolites under various cell states. Under nutrient-replete
      conditions, many lysosomal amino acids are in rapid exchange with those in the
      cytosol. Loss of lysosomal acidification through inhibition of the vacuolar H+
      adenosine triphosphatase (V-ATPase) increased the luminal concentrations of most
      metabolites but had no effect on those of the majority of essential amino acids.
      Instead, nutrient starvation regulates the lysosomal concentrations of these
      amino acids, an effect we traced to regulation of the mechanistic target of
      rapamycin (mTOR) pathway. Inhibition of mTOR strongly reduced the lysosomal
      efflux of most essential amino acids, converting the lysosome into a cellular
      depot for them. These results reveal the dynamic nature of lysosomal metabolites
      and that V-ATPase- and mTOR-dependent mechanisms exist for controlling lysosomal
      amino acid efflux.

PMID- 29074584
TI  - Architecture of eukaryotic mRNA 3'-end processing machinery.
AB  - Newly transcribed eukaryotic precursor messenger RNAs (pre-mRNAs) are processed
      at their 3' ends by the ~1-megadalton multiprotein cleavage and polyadenylation
      factor (CPF). CPF cleaves pre-mRNAs, adds a polyadenylate tail, and triggers
      transcription termination, but it is unclear how its various enzymes are
      coordinated and assembled. Here, we show that the nuclease, polymerase, and
      phosphatase activities of yeast CPF are organized into three modules. Using
      electron cryomicroscopy, we determined a 3.5-angstrom-resolution structure of the
      ~200-kilodalton polymerase module. This revealed four beta propellers, in an
      assembly markedly similar to those of other protein complexes that bind nucleic
      acid. Combined with in vitro reconstitution experiments, our data show that the
      polymerase module brings together factors required for specific and efficient
      polyadenylation, to help coordinate mRNA 3'-end processing.

PMID- 29074586
TI  - Impact of CD14 Polymorphisms on Anti-Apolipoprotein A-1 IgG-Related Coronary
      Artery Disease Prediction in the General Population.
AB  - OBJECTIVE: We aimed to determine whether autoantibodies against apoA-1
      (apolipoprotein A-1; anti-apoA-1 IgG) predict incident coronary artery disease
      (CAD), defined as adjudicated incident myocardial infarction, angina,
      percutaneous coronary revascularization, or bypass grafting, in the general
      population. We further investigated whether this association is modulated by a
      functional CD14 receptor single nucleotide polymorphism. APPROACH AND RESULTS: In
      a prospectively studied, population-based cohort of 5220 subjects (mean age
      52.6+/-10.7 years, 47.4% males), followed over a median period of 5.6 years,
      subjects positive versus negative for anti-apoA-1 IgG presented a total CAD rate
      of 3.9% versus 2.8% (P=0.077) and a nonfatal CAD rate of 3.6% versus 2.3%
      (P=0.018), respectively. After multivariate adjustment for established
      cardiovascular risk factors, the hazard ratios of anti-apoA-1 IgG for total and
      nonfatal CAD were: hazard ratio=1.36 (95% confidence interval, 0.94-1.97;
      P=0.105) and hazard ratio=1.53 (95% confidence interval, 1.03-2.26; P=0.034),
      respectively. In subjects with available genetic data for the C260T rs2569190
      single nucleotide polymorphism in the CD14 receptor gene (n=4247), we observed a
      significant interaction between anti-apoA-1 IgG and rs2569190 allele status with
      regards to CAD risk, with anti-apoA-1 IgG conferring the highest risk for total
      and nonfatal CAD in non-TT carriers, whereas being associated with the lowest
      risk for total and nonfatal CAD in TT homozygotes (P for interaction =0.011 and P
      for interaction =0.033, respectively). CONCLUSIONS: Anti-apoA-1 IgG are
      independent predictors of nonfatal incident CAD in the general population. The
      strength of this association is dependent on a functional polymorphism of the
      CD14 receptor gene, a finding suggesting a gene-autoantibody interaction for the
      development of CAD.

PMID- 29074585
TI  - Delta-5 Fatty Acid Desaturase FADS1 Impacts Metabolic Disease by Balancing
      Proinflammatory and Proresolving Lipid Mediators.
AB  - OBJECTIVE: Human genetic variants near the FADS (fatty acid desaturase) gene
      cluster (FADS1-2-3) are strongly associated with cardiometabolic traits including
      dyslipidemia, fatty liver, type 2 diabetes mellitus, and coronary artery disease.
      However, mechanisms underlying these genetic associations are unclear. APPROACH
      AND RESULTS: Here, we specifically investigated the physiological role of the
      Delta-5 desaturase FADS1 in regulating diet-induced cardiometabolic phenotypes by
      treating hyperlipidemic LDLR (low-density lipoprotein receptor)-null mice with
      antisense oligonucleotides targeting the selective knockdown of Fads1. Fads1
      knockdown resulted in striking reorganization of both omega-6 and omega-3
      polyunsaturated fatty acid levels and their associated proinflammatory and
      proresolving lipid mediators in a highly diet-specific manner. Loss of Fads1
      activity promoted hepatic inflammation and atherosclerosis, yet was associated
      with suppression of hepatic lipogenesis. Fads1 knockdown in isolated macrophages
      promoted classic M1 activation, whereas suppressing alternative M2 activation
      programs, and also altered systemic and tissue inflammatory responses in vivo.
      Finally, the ability of Fads1 to reciprocally regulate lipogenesis and
      inflammation may rely in part on its role as an effector of liver X receptor
      signaling. CONCLUSIONS: These results position Fads1 as an underappreciated
      regulator of inflammation initiation and resolution, and suggest that
      endogenously synthesized arachidonic acid and eicosapentaenoic acid are key
      determinates of inflammatory disease progression and liver X receptor signaling.

PMID- 29074587
TI  - Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral
      Atherosclerosis in Familial Dyslipidemia.
AB  - OBJECTIVE: Bilirubin is a potent antioxidant that has been inversely related to
      cardiovascular disease. There is little information on serum total bilirubin (TB)
      in relation to atherosclerosis in familial dyslipidemia. We assessed the
      association between TB and carotid and femoral atherosclerosis in this high-risk
      group. APPROACH AND RESULTS: We evaluated 464 individuals with familial
      dyslipidemia (56% men; median age, 48 years), 322 with familial
      hypercholesterolemia, and 142 with familial combined hyperlipidemia. Carotid and
      femoral arteries were imaged bilaterally with a standardized ultrasonographic
      protocol. Mean and maximum intima-media thickness and plaque presence (>=1.2 mm)
      and height were recorded. Cross-sectional associations between TB and
      atherosclerosis variables were investigated in multivariable-adjusted models,
      including lipid values and hypolipidemic drug use. Inflammatory markers (C
      reactive protein, total leukocyte count, and lipoprotein[a]) were also
      determined. Increasing TB levels were associated with decreasing intima-media
      thickness of all carotid segments (P<0.05, all). TB also related to carotid
      plaque, present in 78% of individuals, and to plaque burden (>=3 plaques), with
      odds ratios (95% confidence interval) 0.59 (0.36-0.98) and 0.57 (0.34-0.96) for
      each increase of 0.5 mg in TB, respectively. Findings were confirmed in a
      validation cohort of 177 subjects with nonfamilial dyslipidemia. Only the
      familial combined hyperlipidemia group, with higher inflammation-related markers,
      showed an inverse association between TB and femoral plaque height (beta=-0.183;
      P=0.030). CONCLUSIONS: TB was inversely and independently associated with carotid
      plaque burden in familial and nonfamilial dyslipidemia. These findings support
      the use of TB as a biomarker of atherosclerosis in this high-risk group.

PMID- 29074588
TI  - GLP-1 Elicits an Intrinsic Gut-Liver Metabolic Signal to Ameliorate Diet-Induced
      VLDL Overproduction and Insulin Resistance.
AB  - OBJECTIVE: Perturbations in hepatic lipid and very-low-density lipoprotein (VLDL)
      metabolism are involved in the pathogenesis of obesity and hepatic insulin
      resistance. The objective of this study is to delineate the mechanism of
      subdiaphragmatic vagotomy in preventing obesity, hyperlipidemia, and insulin
      resistance. APPROACH AND RESULTS: By subjecting the complete subdiaphragmatic
      vagotomized mice to various nutritional conditions and investigating hepatic de
      novo lipogenesis pathway, we found that complete disruption of subdiaphragmatic
      vagal signaling resulted in a significant decrease of circulating VLDL
      triglyceride compared with the mice obtained sham procedure. Vagotomy further
      prevented overproduction of VLDL-triglyceride induced by an acute fat load and a
      high-fat diet-induced obesity, hyperlipidemia, hepatic steatosis, and glucose
      intolerance. Mechanistic studies revealed that plasma glucagon-like peptide-1 was
      significantly raised in the vagotomized mice, which was associated with
      significant reductions in mRNA and protein expression of SREBP-1c (sterol
      regulatory element-binding protein 1c), SCD-1 (stearoyl-CoA desaturase-1), and
      FASN (fatty acid synthase), as well as enhanced hepatic insulin sensitivity. In
      vitro, treating mouse primary hepatocytes with a glucagon-like peptide-1 receptor
      agonist, exendin-4, for 48 hours inhibited free fatty acid, palmitic acid
      treatment induced de novo lipid synthesis, and VLDL secretion from hepatocytes.
      CONCLUSIONS: Elevation of glucagon-like peptide-1 in vagotomized mice may prevent
      VLDL overproduction and insulin resistance induced by high-fat diet. These novel
      findings, for the first time, delineate an intrinsic gut-liver regulatory circuit
      that is mediated by glucagon-like peptide-1 in regulating hepatic energy
      metabolism.

PMID- 29074591
TI  - Ruxolitinib in ET: not all MPN are equal.

PMID- 29074590
TI  - Deletion of AT2 Receptor Prevents SHP-1-Induced VEGF Inhibition and Improves
      Blood Flow Reperfusion in Diabetic Ischemic Hindlimb.
AB  - OBJECTIVE: Ischemia caused by narrowing of femoral artery is a major cause of
      peripheral arterial disease and morbidity affecting patients with diabetes
      mellitus. We have previously reported that the inhibition of the angiogenic
      response to VEGF (vascular endothelial growth factor) in diabetic mice was
      associated with the increased expression of SHP-1 (SH2 domain-containing
      phosphatase 1), a protein that can be activated by the AT2 (angiotensin II type
      2) receptor. Deletion of AT2 receptor has been shown to promote angiogenesis
      within the ischemic muscle. However, the relative impact of AT2 receptor in
      diabetic condition remains unknown. APPROACH AND RESULTS: Nondiabetic and
      diabetic AT2 null (Atgr2-/Y) mice underwent femoral artery ligation after 2
      months of diabetes mellitus. Blood perfusion was measured every week <=4 weeks
      post-surgery. Expression of the VEGF, SHP-1, and renin-angiotensin pathways was
      evaluated. Blood flow in the ischemic muscle of diabetic Atgr2-/Y mice recovered
      faster and <=80% after 4 weeks compared with 51% recovery in diabetic control
      littermates. Diabetic Atgr2-/Y had reduced apoptotic endothelial cells and
      elevated small vessel formation compared with diabetic Atgr2+/Y mice, as well as
      increased SHP-1 expression and reduced VEGF receptor activity. In endothelial
      cells, high glucose levels and AT2 agonist treatment did not change SHP-1, VEGF,
      and VEGF receptor expression. However, the activity of SHP-1 and its association
      with the VEGF receptors were increased, causing inhibition of the VEGF action in
      endothelial cell proliferation and migration. CONCLUSIONS: Our results suggest
      that the deletion of AT2 receptor reduced SHP-1 activity and restored VEGF
      actions, leading to an increased blood flow reperfusion after ischemia in
      diabetes mellitus.

PMID- 29074592
TI  - Finding active LCH cells in the blood.

PMID- 29074589
TI  - ABCA1-Derived Nascent High-Density Lipoprotein-Apolipoprotein AI and Lipids
      Metabolically Segregate.
AB  - OBJECTIVE: Reverse cholesterol transport comprises cholesterol efflux from ABCA1
      expressing macrophages to apolipoprotein (apo) AI, giving nascent high-density
      lipoprotein (nHDL), esterification of nHDL-free cholesterol (FC), selective
      hepatic extraction of HDL lipids, and hepatic conversion of HDL cholesterol to
      bile salts, which are excreted. We tested this model by identifying the fates of
      nHDL-[3H]FC, [14C] phospholipid (PL), and [125I]apo AI in serum in vitro and in
      vivo. APPROACH AND RESULTS: During in vitro incubation of human serum, nHDL
      [3H]FC and [14C]PL rapidly transfer to HDL and low-density lipoproteins (t1/2=2-7
      minutes), whereas nHDL-[125I]apo AI transfers solely to HDL (t1/2<10 minutes) and
      to the lipid-free form (t1/2>480 minutes). After injection into mice, nHDL-[3H]FC
      and [14C]PL rapidly transfer to liver (t1/2=~2-3 minutes), whereas apo AI clears
      with t1/2=~460 minutes. The plasma nHDL-[3H]FC esterification rate is slow
      (0.46%/h) compared with hepatic uptake. PL transfer protein enhances nHDL-[14C]PL
      but not nHDL-[3H]FC transfer to cultured Huh7 hepatocytes. CONCLUSIONS: nHDL-FC,
      PL, and apo AI enter different pathways in vivo. Most nHDL-[3H]FC and [14C]PL are
      rapidly extracted by the liver via SR-B1 (scavenger receptor class B member 1)
      and spontaneous transfer; hepatic PL uptake is promoted by PL transfer protein.
      nHDL-[125I]apo AI transfers to HDL and to the lipid-free form that can be
      recycled to nHDL formation. Cholesterol esterification by lecithin:cholesterol
      acyltransferase is a minor process in nHDL metabolism. These findings could guide
      the design of therapies that better mobilize peripheral tissue-FC to hepatic
      disposal.

PMID- 29074593
TI  - TP53 mutations in MCL: more therapy is not better.

PMID- 29074594
TI  - A scale of "bad" co-mutations in NPM1-driven AML.

PMID- 29074596
TI  - Atypical monoblasts with micronuclei.

PMID- 29074595
TI  - Ruxolitinib vs best available therapy for ET intolerant or resistant to
      hydroxycarbamide.
AB  - Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis,
      disease-related symptoms, as well as risks of thrombosis, hemorrhage,
      transformation to myelofibrosis, and leukemia. Patients resistant/intolerant to
      hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized
      phase 2 trial of ruxolitinib (JAK1/2 inhibitor) vs best available therapy (BAT)
      in ET and polycythemia vera patients resistant or intolerant to HC. Here,
      findings of MAJIC-ET are reported, where the modified intention-to-treat
      population included 58 and 52 patients randomized to receive ruxolitinib or BAT,
      respectively. There was no evidence of improvement in complete response within 1
      year reported in 27 (46.6%) patients treated with ruxolitinib vs 23 (44.2%) with
      BAT (P = .40). At 2 years, rates of thrombosis, hemorrhage, and transformation
      were not significantly different; however, some disease-related symptoms improved
      in patients receiving ruxolitinib relative to BAT. Molecular responses were
      uncommon; there were 2 complete molecular responses (CMR) and 1 partial molecular
      response in CALR-positive ruxolitinib-treated patients. Transformation to
      myelofibrosis occurred in 1 CMR patient, presumably because of the emergence of a
      different clone, raising questions about the relevance of CMR in ET patients.
      Grade 3 and 4 anemia occurred in 19% and 0% of ruxolitinib vs 0% (both grades) in
      the BAT arm, and grade 3 and 4 thrombocytopenia in 5.2% and 1.7% of ruxolitinib
      vs 0% (both grades) of BAT-treated patients. Rates of discontinuation or
      treatment switching did not differ between the 2 trial arms. The MAJIC-ET trial
      suggests that ruxolitinib is not superior to current second-line treatments for
      ET. This trial was registered at www.isrctn.com as #ISRCTN61925716.

PMID- 29074597
TI  - S-Nitrosoglutathione Reductase Dysfunction Contributes to Obesity-Associated
      Hepatic Insulin Resistance via Regulating Autophagy.
AB  - Obesity is associated with elevated intracellular nitric oxide (NO) production,
      which promotes nitrosative stress in metabolic tissues such as liver and skeletal
      muscle, contributing to insulin resistance. The onset of obesity-associated
      insulin resistance is due, in part, to the compromise of hepatic autophagy, a
      process that leads to lysosomal degradation of cellular components. However, it
      is not known how NO bioactivity might impact autophagy in obesity. Here, we
      establish that S-nitrosoglutathione reductase (GSNOR), a major protein
      denitrosylase, provides a key regulatory link between inflammation and autophagy,
      which is disrupted in obesity and diabetes. We demonstrate that obesity promotes
      S-nitrosylation of lysosomal proteins in the liver, thereby impairing lysosomal
      enzyme activities. Moreover, in mice and humans, obesity and diabetes are
      accompanied by decreases in GSNOR activity, engendering nitrosative stress. In
      mice with a GSNOR deletion, diet-induced obesity increases lysosomal nitrosative
      stress and impairs autophagy in the liver, leading to hepatic insulin resistance.
      Conversely, liver-specific overexpression of GSNOR in obese mice markedly
      enhances lysosomal function and autophagy and, remarkably, improves insulin
      action and glucose homeostasis. Furthermore, overexpression of S-nitrosylation
      resistant variants of lysosomal enzymes enhances autophagy, and pharmacologically
      and genetically enhancing autophagy improves hepatic insulin sensitivity in GSNOR
      deficient hepatocytes. Taken together, our data indicate that obesity-induced
      protein S-nitrosylation is a key mechanism compromising the hepatic autophagy,
      contributing to hepatic insulin resistance.

PMID- 29074598
TI  - Deletion of the Akt/mTORC1 Repressor REDD1 Prevents Visual Dysfunction in a
      Rodent Model of Type 1 Diabetes.
AB  - Diabetes-induced visual dysfunction is associated with significant neuroretinal
      cell death. The current study was designed to investigate the role of the Protein
      Regulated in Development and DNA Damage Response 1 (REDD1) in diabetes-induced
      retinal cell death and visual dysfunction. We recently demonstrated that REDD1
      protein expression was elevated in response to hyperglycemia in the retina of
      diabetic rodents. REDD1 is an important regulator of Akt and mammalian target of
      rapamycin and as such plays a key role in neuronal function and survival. In R28
      retinal cells in culture, hyperglycemic conditions enhanced REDD1 protein
      expression concomitant with caspase activation and cell death. By contrast, in
      REDD1-deficient R28 cells, neither hyperglycemic conditions nor the absence of
      insulin in culture medium were sufficient to promote cell death. In the retinas
      of streptozotocin-induced diabetic mice, retinal apoptosis was dramatically
      elevated compared with nondiabetic controls, whereas no difference was observed
      in diabetic and nondiabetic REDD1-deficient mice. Electroretinogram abnormalities
      observed in b-wave and oscillatory potentials of diabetic wild-type mice were
      also absent in REDD1-deficient mice. Moreover, diabetic wild-type mice exhibited
      functional deficiencies in visual acuity and contrast sensitivity, whereas
      diabetic REDD1-deficient mice had no visual dysfunction. The results support a
      role for REDD1 in diabetes-induced retinal neurodegeneration.

PMID- 29074599
TI  - Diagnosis and management of cystic fibrosis: summary of NICE guidance.

PMID- 29074602
TI  - The forgotten phase of fracture healing: The need to predict nonunion.

PMID- 29074603
TI  - Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD
      Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation.
AB  - Purpose:fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is
      present in 30% of acute myeloid leukemia (AML), and these patients have short
      disease-free survival. FLT3 inhibitors have limited and transient clinical
      activity, and concurrent treatment with inhibitors of parallel or downstream
      signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is
      upregulated downstream of FLT3-ITD and also promotes its signaling in a positive
      feedback loop, suggesting benefit of combined Pim and FLT3
      inhibition.Experimental Design: Combinations of clinically active Pim and FLT3
      inhibitors were studied in vitro and in vivoResults: Concurrent treatment with
      the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable
      concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3
      (FLT3-WT), cell lines. AZD1208 cotreatment increased FLT3 inhibitor-induced
      apoptosis of FLT3-ITD, but not FLT3-WT, cells measured by sub-G1 fraction,
      annexin V labeling, mitochondrial membrane potential, and PARP and caspase-3
      cleavage. Concurrent treatment with AZD1208 and the FLT3 inhibitor quizartinib
      decreased growth of MV4-11 cells, with FLT3-ITD, in mouse xenografts, and
      prolonged survival, enhanced apoptosis of FLT3-ITD primary AML blasts, but not
      FLT3-WT blasts or remission marrow cells, and decreased FLT3-ITD AML blast colony
      formation. Mechanistically, AZD1208 and quizartinib cotreatment decreased
      expression of the antiapoptotic protein Mcl-1. Decrease in Mcl-1 protein
      expression was abrogated by treatment with the proteasome inhibitor MG132, and
      was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel
      mechanism of Mcl-1 regulation in AML.Conclusions: The data support clinical
      testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML. Clin
      Cancer Res; 24(1); 234-47. (c)2017 AACR.

PMID- 29074604
TI  - Prospective Feasibility Trial for Genomics-Informed Treatment in Recurrent and
      Progressive Glioblastoma.
AB  - Purpose: Glioblastoma is an aggressive and molecularly heterogeneous cancer with
      few effective treatment options. We hypothesized that next-generation sequencing
      can be used to guide treatment recommendations within a clinically acceptable
      time frame following surgery for patients with recurrent
      glioblastoma.Experimental Design: We conducted a prospective genomics-informed
      feasibility trial in adults with recurrent and progressive glioblastoma.
      Following surgical resection, genome-wide tumor/normal exome sequencing and tumor
      RNA sequencing were performed to identify molecular targets for potential matched
      therapy. A multidisciplinary molecular tumor board issued treatment
      recommendations based on the genomic results, blood-brain barrier penetration of
      the indicated therapies, drug-drug interactions, and drug safety profiles.
      Feasibility of generating genomics-informed treatment recommendations within 35
      days of surgery was assessed.Results: Of the 20 patients enrolled in the study,
      16 patients had sufficient tumor tissue for analysis. Exome sequencing was
      completed for all patients, and RNA sequencing was completed for 14 patients.
      Treatment recommendations were provided within the study's feasibility time frame
      for 15 of 16 (94%) patients. Seven patients received treatment based on the tumor
      board recommendations. Two patients reached 12-month progression-free survival,
      both adhering to treatments based on the molecular profiling results. One patient
      remained on treatment and progression free 21 months after surgery, 3 times
      longer than the patient's previous time to progression. Analysis of matched
      nonenhancing tissue from 12 patients revealed overlapping as well as novel
      putatively actionable genomic alterations.Conclusions: Use of genome-wide
      molecular profiling is feasible and can be informative for guiding real-time,
      central nervous system-penetrant, genomics-informed treatment recommendations for
      patients with recurrent glioblastoma. Clin Cancer Res; 24(2); 295-305. (c)2017
      AACRSee related commentary by Wick and Kessler, p. 256.

PMID- 29074601
TI  - Inroads into Internalization: Five Years of Endocytic Exploration.

PMID- 29074605
TI  - Allogeneic Human Double Negative T Cells as a Novel Immunotherapy for Acute
      Myeloid Leukemia and Its Underlying Mechanisms.
AB  - Purpose: To explore the potential of ex vivo expanded healthy donor-derived
      allogeneic CD4 and CD8 double-negative cells (DNT) as a novel cellular
      immunotherapy for leukemia patients.Experimental Design: Clinical-grade DNTs from
      peripheral blood of healthy donors were expanded and their antileukemic activity
      and safety were examined using flow cytometry-based in vitro killing assays and
      xenograft models against AML patient blasts and healthy donor-derived
      hematopoietic cells. Mechanism of action was investigated using antibody-mediated
      blocking assays and recombinant protein treatment assays.Results: Expanded DNTs
      from healthy donors target a majority (36/46) of primary AML cells, including 9
      chemotherapy-resistant patient samples in vitro, and significantly reduce the
      leukemia load in patient-derived xenograft models in a DNT donor-unrestricted
      manner. Importantly, allogeneic DNTs do not attack normal hematopoietic cells or
      affect hematopoietic stem/progenitor cell engraftment and differentiation, or
      cause xenogeneic GVHD in recipients. Mechanistically, DNTs express high levels of
      NKG2D and DNAM-1 that bind to cognate ligands preferentially expressed on AML
      cells. Upon recognition of AML cells, DNTs rapidly release IFNgamma, which
      further increases NKG2D and DNAM-1 ligands' expression on AML cells. IFNgamma
      pretreatment enhances the susceptibility of AML cells to DNT-mediated
      cytotoxicity, including primary AML samples that are otherwise resistant to DNTs,
      and the effect of IFNgamma treatment is abrogated by NKG2D and DNAM-1-blocking
      antibodies.Conclusions: This study supports healthy donor-derived allogeneic DNTs
      as a therapy to treat patients with chemotherapy-resistant AML and also reveals
      interrelated roles of NKG2D, DNAM-1, and IFNgamma in selective targeting of AML
      by DNTs. Clin Cancer Res; 24(2); 370-82. (c)2017 AACR.

PMID- 29074606
TI  - Low PD-1 Expression in Cytotoxic CD8+ Tumor-Infiltrating Lymphocytes Confers an
      Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and
      Predictive Value.
AB  - Purpose: The success of immune checkpoint inhibitors strengthens the notion that
      tumor growth and regression are immune regulated. To determine whether distinct
      tissue immune microenvironments differentially affect clinical outcome in non
      small cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor
      infiltrating lymphocytes (TIL) was performed.Experimental Design: Samples from
      resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26
      advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed. PD-L1
      expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25, and
      Granzyme B TILs were immunohistochemically assessed.Results: PD-L1 levels
      inversely correlated with N involvement, although they did not show a
      statistically significant prognostic value in resected patients. The incidence
      and phenotype of TILs differed in SCC versus ADC, in which EGFR and KRAS
      mutations conditioned a different frequency and tissue localization of
      lymphocytes. NSCLC resected patients with high CD8pos lymphocytes lacking PD-1
      inhibitory receptor had a longer overall survival (OS: HR = 2.268; 95% CI, 1.056
      4.871, P = 0.03). PD-1-to-CD8 ratio resulted in a prognostic factor both on
      univariate (HR = 1.952; 95% CI, 1.34-3.12, P = 0.001) and multivariate (HR =
      1.943; 95% CI, 1.38-2.86, P = 0.009) analysis. Moreover, low PD-1 incidence among
      CD8pos cells was a distinctive feature of nivolumab-treated patients, showing
      clinical benefit with a prolonged progression-free survival (PFS: HR = 4.51; 95%
      CI, 1.45-13.94, P = 0.004).Conclusions: In the presence of intrinsic variability
      in PD-L1 expression, the reservoir of PD-1-negative effector T lymphocytes
      provides an immune-privileged microenvironment with a positive impact on survival
      of patients with resected disease and response to immunotherapy in advanced
      NSCLC. Clin Cancer Res; 24(2); 407-19. (c)2017 AACR.

PMID- 29074608
TI  - Medical schools should be prioritising nutrition and lifestyle education.

PMID- 29074607
TI  - Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by
      therapeutic miRNAs: miR-19b-1 role.
AB  - An abnormal acyl-CoA synthetase/stearoyl-CoA desaturase (ACSL/SCD) lipid network
      fuels colon cancer progression, endowing cells with invasive and migratory
      properties. Therapies against this metabolic network may be useful to improve
      clinical outcomes. Because micro-RNAs (miRNAs/miRs) are important epigenetic
      regulators, we investigated novel miRNAs targeting this pro-tumorigenic axis;
      hence to be used as therapeutic or prognostic miRNAs. Thirty-one putative common
      miRNAs were predicted to simultaneously target the three enzymes comprising the
      ACSL/SCD network. Target validation by quantitative RT-PCR, Western blotting, and
      luciferase assays showed miR-544a, miR-142, and miR-19b-1 as major regulators of
      the metabolic axis, ACSL/SCD Importantly, lower miR-19b-1 expression was
      associated with a decreased survival rate in colorectal cancer (CRC) patients,
      accordingly with ACSL/SCD involvement in patient relapse. Finally, miR-19b-1
      regulated the pro-tumorigenic axis, ACSL/SCD, being able to inhibit invasion in
      colon cancer cells. Because its expression correlated with an increased survival
      rate in CRC patients, we propose miR-19b-1 as a potential noninvasive biomarker
      of disease-free survival and a promising therapeutic miRNA in CRC.

PMID- 29074609
TI  - Social Intuition and Social Information in Physical Child Abuse Evaluation and
      Diagnosis.
AB  - BACKGROUND: Poor and minority children with injuries concerning for abuse are
      evaluated and diagnosed for abuse differentially. We hypothesized that 2 steps in
      the decision-making process would influence evaluation and diagnosis: social
      intuition from meeting the family and objective social information associated
      with child abuse risk. METHODS: Between 2009 and 2013, 32 child abuse
      pediatricians (CAPs) submitted 730 child abuse consultations including original
      medical evaluations and diagnoses. CAPs evaluated and diagnosed each other's
      cases. Comparisons of evaluations and diagnoses were made by levels of social
      understanding available to the CAP: meeting the family (social intuition and
      information), reading the case (social information), and reading the case without
      social information. Evaluations were compared with a consensus gold standard by
      using logistic regression modeling adjusting for child and CAP characteristics.
      Diagnostic categories were compared by level of social understanding and
      diagnostic certainty by using contingency tables. RESULTS: CAPs without access to
      social intuition were approximately twice as likely to perform gold standard
      evaluations for neurotrauma and long bone fracture compared with CAPs who met
      families. Diagnostic agreement fell from 73.3% (95% confidence interval [CI]:
      70.1%-76.5%) when social information was present to 66.5% (95% CI: 63.1%-70.0%)
      when social information was restricted. In cases with less certainty, agreement
      dropped to 51.3% (95% CI: 46.0%-56.7%). CONCLUSIONS: Social intuition and
      information play a role in the physical child abuse decision-making process,
      which may contribute to differential diagnosis. Simple interventions including
      decision tools, check lists, and peer review may structure evaluations to ensure
      children's equal treatment.

PMID- 29074610
TI  - Global Health: Preparation for Working in Resource-Limited Settings.
AB  - Trainees and clinicians from high-income countries are increasingly engaging in
      global health (GH) efforts, particularly in resource-limited settings.
      Concomitantly, there is a growing demand for these individuals to be better
      prepared for the common challenges and controversies inherent in GH work. This is
      a state-of-the-art review article in which we outline what is known about the
      current scope of trainee and clinician involvement in GH experiences, highlight
      specific considerations and issues pertinent to GH engagement, and summarize
      preparation recommendations that have emerged from the literature. The article is
      focused primarily on short-term GH experiences, although much of the content is
      also pertinent to long-term work. Suggestions are made for the health care
      community to develop and implement widely endorsed preparation standards for
      trainees, clinicians, and organizations engaging in GH experiences and
      partnerships.

PMID- 29074611
TI  - Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and
      poor prognosis in oral squamous cell carcinoma.
AB  - AIMS: Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the
      sixth most common cancer worldwide and has a high potential for locoregional
      invasion and nodal metastasis. Therefore, discovery of a useful molecular
      biomarker capable of predicting tumour progression and metastasis of OSCC is
      crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4)
      as one of the most upregulated genes in recurrent OSCC using a cDNA microarray
      analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric
      cancer, its expression and clinicopathological roles in OSCC remain unclear.
      METHODS: In this study, we examined ZFAND4 expression by immunohistochemistry in
      214 cases of OSCC. RESULTS: High cytoplasmic expression of ZFAND4 was observed in
      45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly
      associated with metastasis to the lymph nodes (p=0.0429) and distant organs
      (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable
      prognosis compared with patients with low expression of ZFAND4 (p<0.0001).
      Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for
      OSCC as determined by multivariate analysis using the Cox proportional hazards
      model (p<0.0001). CONCLUSIONS: These results suggest that ZFAND4 is a useful
      marker for predicting metastasis and poor prognosis in patients with OSCC.

PMID- 29074612
TI  - AIP mutations in Brazilian patients with sporadic pituitary adenomas: a single
      center evaluation.
AB  - Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations (AIPmut) are
      the most frequent germline mutations found in apparently sporadic pituitary
      adenomas (SPA). Our aim was to evaluate the frequency of AIPmut among young
      Brazilian patients with SPA. We performed an observational cohort study between
      2013 and 2016 in a single referral center. AIPmut screening was carried out in
      132 SPA patients with macroadenomas diagnosed up to 40 years or in adenomas of
      any size diagnosed until 18 years of age. Twelve tumor samples were also
      analyzed. Leukocyte DNA and tumor tissue DNA were sequenced for the entire AIP
      coding region for evaluation of mutations. Eleven (8.3%) of the 132 patients had
      AIPmut, comprising 9/74 (12%) somatotropinomas, 1/38 (2.6%) prolactinoma, 1/10
      (10%) corticotropinoma and no non-functioning adenomas. In pediatric patients
      (<=18 years), AIPmut frequency was 13.3% (2/15). Out of the 5 patients with
      gigantism, two had AIPmut, both truncating mutations. The Y268* mutation was
      described in Brazilian patients and the K273Rfs*30 mutation is a novel mutation
      in our patient. No somatic AIP mutations were found in the 12 tumor samples. A
      tumor sample from an acromegaly patient harboring the A299V AIPmut showed loss of
      heterozygosity. In conclusion, AIPmut frequency in SPA Brazilian patients is
      similar to other populations. Our study identified two mutations exclusively
      found in Brazilians and also shows, for the first time, loss of heterozygosity in
      tumor DNA from an acromegaly patient harboring the A299V AIPmut Our findings
      corroborate previous observations that AIPmut screening should be performed in
      young patients with SPA.

PMID- 29074614
TI  - Plans to sell off NHS land-ludicrous financial idiocy.

PMID- 29074613
TI  - The incidence of congenital hypothyroidism (CH) in Guangxi, China and the
      predictors of permanent and transient CH.
AB  - BACKGROUND: The incidence of congenital hypothyroidism (CH) differs significantly
      among different ethnicities and regions, and early differentiation of transient
      CH is important to avoid unnecessary prolonged treatment with L-T4. OBJECTIVE: To
      investigate the incidence of CH based on the newborn screening program in Guangxi
      Zhuang Autonomous Region, China, and to analyze the predictors that might allow
      for an early differentiation between permanent (P) and transient (T) CH. DESIGN
      AND METHODS: Data from newborn screening program over a seven-year period
      (January 2009 to January 2016) at Guangxi Maternal and Child Health Hospital are
      analyzed. Blood samples were collected on filter paper between 3 and 7 days after
      birth, and TSH level was measured by time-resolved fluorescence assay.
      Individuals with increased TSH (TSH >= 8 IU/L) levels detected by newborn
      screening were recalled for further evaluation. Serum TSH, FT3 and FT4 were
      determined by electrochemiluminescence assay using venous blood samples.
      Diagnosis of CH is based on elevated TSH levels (>10 IU/L) and decreased FT4
      levels (<12 pmol/L). Patients with elevated TSH levels and normal FT4 levels were
      diagnosed as hyperthyrotropinemia. Permanent or transient CH was determined by
      using the results of thyroid function tests after temporary withdrawal of L-T4
      therapy at approximately 2-3 years of age. RESULTS: Among 1,238,340 infants in
      the newborn screening program, 14,443 individuals were recalled for reevaluation
      (re-call rate 1.18%), 911 and 731 individuals were subsequently determined to
      have hyperthyrotropinemia and CH respectively; thus, a prevalence of 1:1359 and
      1:1694 for hyperthyrotropinemia and CH. Of the 731 patients with CH, 161 patients
      were diagnosed with permanent CH (PCH), and 159 patients were diagnosed with
      transient CH (TCH), the other 411 patients are too young to determine their
      subtypes. Patients with PCH required an increasing dose of L-T4 during the first
      few years, whereas patients with TCH required a decreased dose of L-T4. The TSH
      levels at diagnosis and the dose of L-T4 used were significantly higher in PCH
      cases than in transient cases. The FT4 levels at diagnosis were significantly
      lower in PCH cases than in TCH cases. The TSH levels at diagnosis, FT4 levels at
      diagnosis and L-T4 doses at 90 days were evaluated as predictors for
      differentiating PCH and TCH, and their accuracy at their respective optimal
      cutoffs were determined to be 60.6%, 66.7% and 93.9%, respectively. CONCLUSIONS:
      The CH incidence in Guangxi Zhuang Autonomous Region is slightly higher (1:1694)
      compared to the worldwide levels (1/2000-1/4000). The PCH and TCH ratio is close
      to 1; thus, the estimated PCH incidence is 1/3388, which is similar to reported
      worldwide average incidence (1/3000). The L-T4 dose required at 90 days (>30
      MUg/day) has the highest predictive value for PCH. Earlier differentiation of PCH
      and TCH helps to determine appropriate treatment course.

PMID- 29074615
TI  - Estrogen is an important mediator of mast cell activation in ovarian
      endometriomas.
AB  - Endometriosis is an estrogen-dependent disease. Previous research has shown that
      abnormal enzymes associated with estrogen (E2) metabolism and an increased number
      of mast cells (MCs) in endometriomas are implicated in the pathogenesis of
      endometriosis. However, it remains unclear how MCs mediate the role of E2 in
      endometriosis. Accordingly, we investigated whether E2 was associated with the
      number of MCs, and the rate of degranulation, in local ovarian endometriomas, as
      well as the role of E2 on MCs during the pathogenesis of endometriosis. Using
      enzyme-linked immunosorbent assay and immunohistochemistry, we found that
      concentrations of E2, and the number and activity of MCs, were significantly
      higher in ovarian endometriomas than in controls, and that these parameters were
      correlated with the severity of endometriosis-associated dysmenorrhea. By
      measuring the release of hexosaminidase, we found that the rate of RBL2H3 cell
      degranulation increased after E2 treatment. Furthermore, activation of RBL2H3
      cells by E2 was found to trigger the release of biologically active nerve growth
      factor, which promotes neurite outgrowth in PC12 cells and also sensitizes dorsal
      root ganglion cells via upregulation of Nav1.8 and transient receptor potential
      cation channel (subfamily V member 1) expression levels. When treated with E2,
      endometriotic cells could promote RBL2H3 cell recruitment by upregulating
      expression levels of stem cell factor, transforming growth factor-beta and
      monocyte chemoattractant protein-1; these observations were not evident with
      control endometrial cells. Thus, elevated E2 concentrations may be a key factor
      for degranulation and recruitment of MCs in ovarian endometriomas, which play a
      key role in endometriosis-associated dysmenorrhea.

PMID- 29074616
TI  - Resveratrol: A novel type of topoisomerase II inhibitor.
AB  - Resveratrol, a polyphenol found in various plant sources, has gained attention as
      a possible agent responsible for the purported health benefits of certain foods,
      such as red wine. Despite annual multi-million dollar market sales as a
      nutriceutical, there is little consensus about the physiological roles of
      resveratrol. One suggested molecular target of resveratrol is eukaryotic
      topoisomerase II (topo II), an enzyme essential for chromosome segregation and
      DNA supercoiling homeostasis. Interestingly, resveratrol is chemically similar to
      ICRF-187, a clinically approved chemotherapeutic that stabilizes an ATP-dependent
      dimerization interface in topo II to block enzyme activity. Based on this
      similarity, we hypothesized that resveratrol may antagonize topo II by a similar
      mechanism. Using a variety of biochemical assays, we find that resveratrol indeed
      acts through the ICRF-187 binding locus, but that it inhibits topo II by
      preventing ATPase domain dimerization rather than stabilizing it. This work
      presents the first comprehensive analysis of the biochemical effects of both ICRF
      187 and resveratrol on the human isoforms of topo II, and reveals a new mode for
      the allosteric regulation of topo II through modulation of ATPase status. Natural
      polyphenols related to resveratrol that have been shown to impact topo II
      function may operate in a similar manner.

PMID- 29074617
TI  - Organelle-specific single-molecule imaging of alpha4beta2 nicotinic receptors
      reveals the effect of nicotine on receptor assembly and cell-surface trafficking.
AB  - Nicotinic acetylcholine receptors (nAChRs) assemble in the endoplasmic reticulum
      (ER) and traffic to the cell surface as pentamers composed of alpha and beta
      subunits. Many nAChR subtypes can assemble with varying subunit ratios, giving
      rise to multiple stoichiometries exhibiting different subcellular localization
      and functional properties. In addition to the endogenous neurotransmitter
      acetylcholine, nicotine also binds and activates nAChRs and influences their
      trafficking and expression on the cell surface. Currently, no available technique
      can specifically elucidate the stoichiometry of nAChRs in the ER versus those in
      the plasma membrane. Here, we report a method involving single-molecule
      fluorescence measurements to determine the structural properties of these
      membrane proteins after isolation in nanoscale vesicles derived from specific
      organelles. These cell-derived nanovesicles allowed us to separate single
      membrane receptors while maintaining them in their physiological environment.
      Sorting the vesicles according to the organelle of origin enabled us to determine
      localized differences in receptor structural properties, structural influence on
      transport between organelles, and changes in receptor assembly within
      intracellular organelles. These organelle-specific nanovesicles revealed that one
      structural isoform of the alpha4beta2 nAChR was preferentially trafficked to the
      cell surface. Moreover, nicotine altered nAChR assembly in the ER, resulting in
      increased production of the receptor isoform that traffics more efficiently to
      the cell surface. We conclude that the combined effects of the increased assembly
      of one nAChR stoichiometry and its preferential trafficking likely drive the up
      regulation of nAChRs on the cell surface upon nicotine exposure.

PMID- 29074618
TI  - Epidermal growth factor receptors containing a single tyrosine in their C
      terminal tail bind different effector molecules and are signaling-competent.
AB  - The EGF receptor is a classic receptor tyrosine kinase. It contains nine
      tyrosines in its C-terminal tail, many of which are phosphorylated and bind
      proteins containing SH2 or phosphotyrosine-binding (PTB) domains. To determine
      how many and which tyrosines are required to enable EGF receptor-mediated
      signaling, we generated a series of EGF receptors that contained only one
      tyrosine in their C-terminal tail. Assays of the signaling capabilities of these
      single-Tyr EGF receptors indicated that they can activate a range of downstream
      signaling pathways, including MAP kinase and Akt. The ability of the single-Tyr
      receptors to signal correlated with their ability to bind Gab1 (Grb2-associated
      binding protein 1). However, Tyr-992 appeared to be almost uniquely required to
      observe activation of phospholipase Cgamma. These results demonstrate that
      multiply phosphorylated receptors are not required to support most EGF-stimulated
      signaling but identify Tyr-992 and its binding partners as a unique node within
      the network. We also studied the binding of the isolated SH2 domain of Grb2
      (growth factor receptor-bound protein 2) and the isolated PTB domain of Shc (SHC
      adaptor protein) to the EGF receptor. Although these adapter proteins bound
      readily to wild-type EGF receptor, they bound poorly to the single-Tyr EGF
      receptors, even those that bound full-length Grb2 and Shc well. This suggests
      that in addition to pTyr-directed associations, secondary interactions between
      the tail and regions of the adapter proteins outside of the SH2/PTB domains are
      important for stabilizing the binding of Grb2 and Shc to the single-Tyr EGF
      receptors.

PMID- 29074619
TI  - Presynaptic mGluR5 receptor controls glutamatergic input through protein kinase C
      NMDA receptors in paclitaxel-induced neuropathic pain.
AB  - Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in
      many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary
      afferent terminals are known to be critically involved in chemotherapy-induced
      chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR
      activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a
      role in synaptic plasticity and NMDAR regulation. Here we report that the Group I
      mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the
      frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude
      of monosynaptic EPSCs evoked from the dorsal root. DHPG also reduced the paired
      pulse ratio of evoked EPSCs in spinal dorsal horn neurons. These effects were
      blocked by the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine
      (MPEP), but not by an mGluR1 antagonist. MPEP normalized the frequency of
      miniature EPSCs and the amplitude of evoked EPSCs in paclitaxel-treated rats but
      had no effect in vehicle-treated rats. Furthermore, mGluR5 protein levels in the
      dorsal root ganglion and spinal cord synaptosomes were significantly higher in
      paclitaxel- than in vehicle-treated rats. Inhibiting protein kinase C (PKC) or
      blocking NMDARs abolished DHPG-induced increases in the miniature EPSC frequency
      of spinal dorsal horn neurons in vehicle- and paclitaxel-treated rats. Moreover,
      intrathecal administration of MPEP reversed pain hypersensitivity caused by
      paclitaxel treatment. Our findings suggest that paclitaxel-induced painful
      neuropathy is associated with increased presynaptic mGluR5 activity at the spinal
      cord level, which serves as upstream signaling for PKC-mediated tonic activation
      of NMDARs. mGluR5 is therefore a promising target for reducing chemotherapy
      induced neuropathic pain.

PMID- 29074620
TI  - The natural product mensacarcin induces mitochondrial toxicity and apoptosis in
      melanoma cells.
AB  - Mensacarcin is a highly oxygenated polyketide that was first isolated from soil
      dwelling Streptomyces bacteria. It exhibits potent cytostatic properties (mean of
      50% growth inhibition = 0.2 MUm) in almost all cell lines of the National Cancer
      Institute (NCI)-60 cell line screen and relatively selective cytotoxicity against
      melanoma cells. Moreover, its low COMPARE correlations with known standard
      antitumor agents indicate a unique mechanism of action. Effective therapies for
      managing melanoma are limited, so we sought to investigate mensacarcin's unique
      cytostatic and cytotoxic effects and its mode of action. By assessing
      morphological and biochemical features, we demonstrated that mensacarcin
      activates caspase-3/7-dependent apoptotic pathways and induces cell death in
      melanoma cells. Upon mensacarcin exposure, SK-Mel-28 and SK-Mel-5 melanoma cells,
      which have the BRAFV600E mutation associated with drug resistance, showed
      characteristic chromatin condensation as well as distinct poly(ADP
      ribose)polymerase-1 cleavage. Flow cytometry identified a large population of
      apoptotic melanoma cells, and single-cell electrophoresis indicated that
      mensacarcin causes genetic instability, a hallmark of early apoptosis. To
      visualize mensacarcin's subcellular localization, we synthesized a fluorescent
      mensacarcin probe that retained activity. The natural product probe was localized
      to mitochondria within 20 min of treatment. Live-cell bioenergetic flux analysis
      confirmed that mensacarcin disturbs energy production and mitochondrial function
      rapidly. The subcellular localization of the fluorescently labeled mensacarcin
      together with its unusual metabolic effects in melanoma cells provide evidence
      that mensacarcin targets mitochondria. Mensacarcin's unique mode of action
      suggests that it may be a useful probe for examining energy metabolism,
      particularly in BRAF-mutant melanoma, and represent a promising lead for the
      development of new anticancer drugs.

PMID- 29074621
TI  - The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against
      high-fat diet-induced obesity and type II diabetes.
AB  - The transient receptor potential canonical channel-1 (TRPC1) is a Ca2+-permeable
      channel found in key metabolic organs and tissues, including the hypothalamus,
      adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of
      cellular energy metabolism resulting in insulin resistance thereby leading to
      diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1
      is involved in exercise-induced insulin sensitivity. The role of TRPC1 in
      adiposity and obesity-associated metabolic diseases has not yet been determined.
      Our results show that TRPC1 functions as a major Ca2+ entry channel in
      adipocytes. We have also shown that fat mass and fasting glucose concentrations
      were lower in TRPC1 KO mice that were fed a high-fat (HF) (45% fat) diet and
      exercised as compared with WT mice fed a HF diet and exercised. Adipocyte numbers
      were decreased in both subcutaneous and visceral adipose tissue of TRPC1 KO mice
      fed a HF diet and exercised. Finally, autophagy markers were decreased and
      apoptosis markers increased in TRPC1 KO mice fed a HF diet and exercised.
      Overall, these findings suggest that TRPC1 plays an important role in the
      regulation of adiposity via autophagy and apoptosis and that TRPC1 inhibits the
      positive effect of exercise on type II diabetes risk under a HF diet-induced
      obesity environment.

PMID- 29074623
TI  - Conformational dynamics of the TTD-PHD histone reader module of the UHRF1
      epigenetic regulator reveals multiple histone-binding states, allosteric
      regulation, and druggability.
AB  - UHRF1 is a key mediator of inheritance of epigenetic DNA methylation patterns
      during cell division and is a putative target for cancer therapy. Recent studies
      indicate that interdomain interactions critically influence UHRF1's chromatin
      binding properties, including allosteric regulation of its histone binding. Here,
      using an integrative approach that combines small angle X-ray scattering, NMR
      spectroscopy, and molecular dynamics simulations, we characterized the dynamics
      of the tandem tudor domain-plant homeodomain (TTD-PHD) histone reader module,
      including its 20-residue interdomain linker. We found that the apo TTD-PHD module
      in solution comprises a dynamic ensemble of conformers, approximately half of
      which are compact conformations, with the linker lying in the TTD peptide-binding
      groove. These compact conformations are amenable to cooperative, high-affinity
      histone binding. In the remaining conformations, the linker position was in flux,
      and the reader adopted both extended and compact states. Using a small-molecule
      fragment screening approach, we identified a compound, 4-benzylpiperidine-1
      carboximidamide, that binds to the TTD groove, competes with linker binding, and
      promotes open TTD-PHD conformations that are less efficient at H3K9me3 binding.
      Our work reveals a mechanism by which the dynamic TTD-PHD module can be
      allosterically targeted with small molecules to modulate its histone reader
      function for therapeutic or experimental purposes.

PMID- 29074622
TI  - Replication origin-flanking roadblocks reveal origin-licensing dynamics and
      altered sequence dependence.
AB  - In eukaryotes, DNA replication initiates from multiple origins of replication for
      timely genome duplication. These sites are selected by origin licensing, during
      which the core enzyme of the eukaryotic DNA replicative helicase, the Mcm2-7
      (minichromosome maintenance) complex, is loaded at each origin. This origin
      licensing requires loading two Mcm2-7 helicases around origin DNA in a head-to
      head orientation. Current models suggest that the origin-recognition complex
      (ORC) and cell-division cycle 6 (Cdc6) proteins recognize and encircle origin DNA
      and assemble an Mcm2-7 double-hexamer around adjacent double-stranded DNA. To
      test this model and assess the location of Mcm2-7 initial loading, we placed DNA
      protein roadblocks at defined positions adjacent to the essential ORC-binding
      site within Saccharomyces cerevisiae origin DNA. Roadblocks were made either by
      covalent cross-linking of the HpaII methyltransferase to DNA or through binding
      of a transcription activator-like effector (TALE) protein. Contrary to the sites
      of Mcm2-7 recruitment being precisely defined, only single roadblocks that
      inhibited ORC-DNA binding showed helicase loading defects. We observed inhibition
      of helicase loading without inhibition of ORC-DNA binding only when roadblocks
      were placed on both sides of the origin to restrict sliding of a helicase-loading
      intermediate. Consistent with a sliding helicase-loading intermediate, when
      either one of the flanking roadblocks was eliminated, the remaining roadblock had
      no effect on helicase loading. Interestingly, either origin-flanking nucleosomes
      or roadblocks resulted in helicase loading being dependent on an additional
      origin sequence known to be a weaker ORC-DNA-binding site. Together, our findings
      support a model in which sliding helicase-loading intermediates increase the
      flexibility of the DNA sequence requirements for origin licensing.

PMID- 29074624
TI  - De-adoption and exnovation in the use of carotid revascularization: retrospective
      cohort study.
AB  - Objective To determine physician characteristics associated with exnovation
      (scaling back on use) and de-adoption (abandoning use) of carotid
      revascularization.Design Retrospective longitudinal cohort study.Setting Medicare
      claims linked to the Doximity database provider registry, 2006-13.Participants
      9158 physicians who performed carotid revascularization on Medicare patients
      between 2006 and 2013.Main outcome measures The primary outcomes were the number
      of carotid revascularization procedures for each physician per year at the end of
      the sample period, and the percentage change in the volume of carotid
      revascularization procedures.Results At baseline (2006-07), 9158 physicians
      performed carotid revascularization. By 2012-13 the use of revascularization in
      this cohort had declined by 37.7%, with two thirds attributable to scaling back
      (exnovation) rather than dropping the procedure entirely (de-adoption). Compared
      with physicians with fewer than 12 years of experience, those with more than 25
      years of experience decreased use by an additional 23.0% (95% confidence interval
      -36.7% to -9.2%). The lowest rates of decline occurred in physicians specializing
      in vascular or thoracic surgery, for whom the procedures accounted for a large
      share of revenue. Physicians with high proportions of patients aged more than 80
      years or with asymptomatic carotid stenosis were less likely to reduce their use
      of carotid revascularization.Conclusion Surgeons with more experience and the
      lowest share in carotid revascularization practice reduced their use of the
      procedure the most. These practice factors should be considered in quality
      improvement efforts when the evidence base evolves away from a specific
      treatment.

PMID- 29074626
TI  - Human THO-Sin3A interaction reveals new mechanisms to prevent R-loops that cause
      genome instability.
AB  - R-loops, formed by co-transcriptional DNA-RNA hybrids and a displaced DNA single
      strand (ssDNA), fulfill certain positive regulatory roles but are also a source
      of genomic instability. One key cellular mechanism to prevent R-loop accumulation
      centers on the conserved THO/TREX complex, an RNA-binding factor involved in
      transcription elongation and RNA export that contributes to messenger
      ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear.
      To understand how THO restrains harmful R-loops, we searched for new THO
      interacting factors. We found that human THO interacts with the Sin3A histone
      deacetylase complex to suppress co-transcriptional R-loops, DNA damage, and
      replication impairment. Functional analyses show that histone hypo-acetylation
      prevents accumulation of harmful R-loops and RNA-mediated genomic instability.
      Diminished histone deacetylase activity in THO- and Sin3A-depleted cell lines
      correlates with increased R-loop formation, genomic instability, and replication
      fork stalling. Our study thus uncovers physical and functional crosstalk between
      RNA-binding factors and chromatin modifiers with a major role in preventing R
      loop formation and RNA-mediated genome instability.

PMID- 29074627
TI  - Isoform-specific localization of DNMT3A regulates DNA methylation fidelity at
      bivalent CpG islands.
AB  - DNA methylation is a prevalent epigenetic modification involved in
      transcriptional regulation and essential for mammalian development. While the
      genome-wide distribution of this mark has been studied to great detail, the
      mechanisms responsible for its correct deposition, as well as the cause for its
      aberrant localization in cancers, have not been fully elucidated. Here, we have
      compared the activity of individual DNMT3A isoforms in mouse embryonic stem and
      neuronal progenitor cells and report that these isoforms differ in their genomic
      binding and DNA methylation activity at regulatory sites. We identify that the
      longer isoform DNMT3A1 preferentially localizes to the methylated shores of
      bivalent CpG island promoters in a tissue-specific manner. The isoform-specific
      targeting of DNMT3A1 coincides with elevated hydroxymethylcytosine (5-hmC)
      deposition, suggesting an involvement of this isoform in mediating turnover of
      DNA methylation at these sites. Through genetic deletion and rescue experiments,
      we demonstrate that this isoform-specific recruitment plays a role in de novo DNA
      methylation at CpG island shores, with potential implications on H3K27me3
      mediated regulation of developmental genes.

PMID- 29074630
TI  - Reply.

PMID- 29074628
TI  - Payments by US pharmaceutical and medical device manufacturers to US medical
      journal editors: retrospective observational study.
AB  - Objective To estimate financial payments from industry to US journal
      editors.Design Retrospective observational study.Setting 52 influential (high
      impact factor for their specialty) US medical journals from 26 specialties and US
      Open Payments database, 2014.Participants 713 editors at the associate level and
      above identified from each journal's online masthead.Main outcome measures All
      general payments (eg, personal income) and research related payments from
      pharmaceutical and medical device manufacturers to eligible physicians in 2014.
      Percentages of editors receiving payments and the magnitude of such payments were
      compared across journals and by specialty. Journal websites were also reviewed to
      determine if conflict of interest policies for editors were readily
      accessible.Results Of 713 eligible editors, 361 (50.6%) received some (>$0)
      general payments in 2014, and 139 (19.5%) received research payments. The median
      general payment was $11 (L8; ?9) (interquartile range $0-2923) and the median
      research payment was $0 ($0-0). The mean general payment was $28 136 (SD $415
      045), and the mean research payment was $37 963 (SD $175 239). The highest median
      general payments were received by journal editors from endocrinology ($7207, $0
      85 816), cardiology ($2664, $0-12 912), gastroenterology ($696, $0-20 002),
      rheumatology ($515, $0-14 280), and urology ($480, $90-669). For high impact
      general medicine journals, median payments were $0 ($0-14). A review of the 52
      journal websites revealed that editor conflict of interest policies were readily
      accessible (ie, within five minutes) for 17/52 (32.7%) of journals.Conclusions
      Industry payments to journal editors are common and often large, particularly for
      certain subspecialties. Journals should consider the potential impact of such
      payments on public trust in published research.

PMID- 29074631
TI  - Economic Considerations in MR Imaging of Patients with Cardiac Devices.

PMID- 29074629
TI  - Obesity and gynaecological and obstetric conditions: umbrella review of the
      literature.
AB  - Objective To study the strength and validity of associations between adiposity
      and risk of any type of obstetric or gynaecological conditions.Design An umbrella
      review of meta-analyses.Data sources PubMed, Cochrane database of systematic
      reviews, manual screening of references for systematic reviews or meta-analyses
      of observational and interventional studies evaluating the association between
      adiposity and risk of any obstetrical or gynaecological outcome.Main outcomes
      Meta-analyses of cohort studies on associations between indices of adiposity and
      obstetric and gynaecological outcomes.Data synthesis Evidence from observational
      studies was graded into strong, highly suggestive, suggestive, or weak based on
      the significance of the random effects summary estimate and the largest study in
      the included meta-analysis, the number of cases, heterogeneity between studies,
      95% prediction intervals, small study effects, excess significance bias, and
      sensitivity analysis with credibility ceilings. Interventional meta-analyses were
      assessed separately.Results 156 meta-analyses of observational studies were
      included, investigating associations between adiposity and risk of 84 obstetric
      or gynaecological outcomes. Of the 144 meta-analyses that included cohort
      studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was
      associated with a higher risk of endometrial cancer, ovarian cancer, antenatal
      depression, total and emergency caesarean section, pre-eclampsia, fetal
      macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21
      (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit
      increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to
      4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of
      these eight outcomes were also assessed in meta-analyses of trials evaluating
      weight loss interventions. These interventions significantly reduced the risk of
      caesarean section and pre-eclampsia, whereas there was no evidence of association
      with fetal macrosomia.Conclusions Although the associations between adiposity and
      obstetric and gynaecological outcomes have been extensively studied, only a
      minority were considered strong and without hints of bias.

PMID- 29074632
TI  - Improved Spatiotemporal Resolution of Dynamic Susceptibility Contrast Perfusion
      MRI in Brain Tumors Using Simultaneous Multi-Slice Echo-Planar Imaging.
AB  - DSC perfusion MR imaging in brain tumors requires a trade-off between spatial and
      temporal resolution, resulting in less spatial coverage to meet the temporal
      resolution requirements for accurate relative CBV estimation. DSC-MR imaging
      could potentially benefit from the advantages associated with simultaneous multi
      slice imaging, including increased spatiotemporal resolution. In the current
      article, we demonstrate how simultaneous multi-slice EPI can be used to improve
      DSC-MR imaging spatiotemporal resolution in patients with glioblastoma.

PMID- 29074633
TI  - Comparison between the Prebolus T1 Measurement and the Fixed T1 Value in Dynamic
      Contrast-Enhanced MR Imaging for the Differentiation of True Progression from
      Pseudoprogression in Glioblastoma Treated with Concurrent Radiation Therapy and
      Temozolomide Chemotherapy.
AB  - BACKGROUND AND PURPOSE: Glioblastoma is the most common primary brain malignancy
      and differentiation of true progression from pseudoprogression is clinically
      important. Our purpose was to compare the diagnostic performance of dynamic
      contrast-enhanced pharmacokinetic parameters using the fixed T1 and measured T1
      on differentiating true from pseudoprogression of glioblastoma after
      chemoradiation with temozolomide. MATERIALS AND METHODS: This retrospective study
      included 37 patients with histopathologically confirmed glioblastoma with new
      enhancing lesions after temozolomide chemoradiation defined as true progression
      (n = 15) or pseudoprogression (n = 22). Dynamic contrast-enhanced pharmacokinetic
      parameters, including the volume transfer constant, the rate transfer constant,
      the blood plasma volume per unit volume, and the extravascular extracellular
      space per unit volume, were calculated by using both the fixed T1 of 1000 ms and
      measured T1 by using the multiple flip-angle method. Intra- and interobserver
      reproducibility was assessed by using the intraclass correlation coefficient.
      Dynamic contrast-enhanced pharmacokinetic parameters were compared between the 2
      groups by using univariate and multivariate analysis. The diagnostic performance
      was evaluated by receiver operating characteristic analysis and leave-one-out
      cross validation. RESULTS: The intraclass correlation coefficients of all the
      parameters from both T1 values were fair to excellent (0.689-0.999). The volume
      transfer constant and rate transfer constant from the fixed T1 were significantly
      higher in patients with true progression (P = .048 and .010, respectively).
      Multivariate analysis revealed that the rate transfer constant from the fixed T1
      was the only independent variable (OR, 1.77 * 105) and showed substantial
      diagnostic power on receiver operating characteristic analysis (area under the
      curve, 0.752; P = .002). The sensitivity and specificity on leave-one-out cross
      validation were 73.3% (11/15) and 59.1% (13/20), respectively. CONCLUSIONS: The
      dynamic contrast-enhanced parameter of rate transfer constant from the fixed T1
      acted as a preferable marker to differentiate true progression from
      pseudoprogression.

PMID- 29074635
TI  - Patterns of Sonographically Detectable Echogenic Foci in Pediatric Thyroid
      Carcinoma with Corresponding Histopathology: An Observational Study.
AB  - BACKGROUND AND PURPOSE: Small echogenic foci within pediatric thyroid nodules are
      commonly seen by ultrasound and are one of the features used to determine the
      level of suspicion for malignancy. These are sometimes termed
      "microcalcifications," but their relation with malignancy is controversial due to
      the lack of standard terminology. Our aim was to evaluate sonographic patterns of
      echogenic foci in malignant pediatric thyroid nodules and describe the
      distribution of corresponding psammoma bodies and other histopathologic findings
      in thyroidectomy specimens. MATERIALS AND METHODS: Ultrasounds of 15
      pathologically proved malignant thyroid nodules in children were retrospectively
      reviewed by 2 radiologists who separately classified echogenic foci into the 4
      morphologic patterns described in the American College of Radiology Thyroid
      Imaging, Reporting and Data System and noted their presence and distribution.
      Interobserver agreement was assessed, and consensus was reached for nodules for
      which there was disagreement. Surgical pathology findings from thyroidectomy
      specimens were retrospectively reviewed for the presence and distribution of
      psammomatous and dystrophic/stromal calcifications and eosinophilic/sticky
      colloid. Ultrasound and histopathologic ratings were compared, and frequencies
      and percentages corresponding to observed agreement levels were calculated.
      RESULTS: Interobserver agreement between radiologists' sonographic assessments
      for the presence and distribution of echogenic foci ranged from 53% to 100% for
      all categories. Punctate echogenic foci were present in all nodules, and
      macrocalcifications, in 27%. Histopathology of the 15 nodules revealed that only
      4 (27%) had psammomatous calcifications, while 9 (60%) had stromal calcifications
      and 8 (53%) had sticky colloid. CONCLUSIONS: Sonographically detectable echogenic
      foci in malignant pediatric thyroid nodules can be reliably classified on the
      basis of American College of Radiology Thyroid Imaging, Reporting and Data
      System, with punctate echogenic foci composing the most common subtype. These
      echogenic foci do not represent psammomatous calcifications most of the time;
      instead, more than half of the malignant thyroid nodules with echogenic foci
      contained stromal calcifications or sticky colloid.

PMID- 29074634
TI  - Do Fluid-Attenuated Inversion Recovery Vascular Hyperintensities Represent Good
      Collaterals before Reperfusion Therapy?
AB  - BACKGROUND AND PURPOSE: In acute ischemic stroke, whether FLAIR vascular
      hyperintensities represent good or poor collaterals remains controversial. We
      hypothesized that extensive FLAIR vascular hyperintensities correspond to good
      collaterals, as indirectly assessed by the hypoperfusion intensity ratio.
      MATERIALS AND METHODS: We included 244 consecutive patients eligible for
      reperfusion therapy with MCA stroke and pretreatment MR imaging with both FLAIR
      and PWI. The FLAIR vascular hyperintensity score was based on ASPECTS, ranging
      from 0 (no FLAIR vascular hyperintensity) to 7 (FLAIR vascular hyperintensities
      abutting all ASPECTS cortical areas). The hypoperfusion intensity ratio was
      defined as the ratio of the time-to-maximum >10-second over time-to-maximum >6
      second lesion volumes. The median hypoperfusion intensity ratio was used to
      dichotomize good (low hypoperfusion intensity ratio) versus poor (high
      hypoperfusion intensity ratio) collaterals. We then studied the association
      between FLAIR vascular hyperintensity extent and hypoperfusion intensity ratio.
      RESULTS: Hypoperfusion was present in all patients, with a median hypoperfusion
      intensity ratio of 0.35 (interquartile range, 0.19-0.48). The median FLAIR
      vascular hyperintensity score was 4 (interquartile range, 3-5). The FLAIR
      vascular hyperintensities were more extensive in patients with good collaterals
      (hypoperfusion intensity ratio <=0.35) than with poor collaterals (hypoperfusion
      intensity ratio >0.35; P for Trend = .016). The FLAIR vascular hyperintensity
      score was independently associated with good collaterals (P for Trend = .002).
      CONCLUSIONS: In patients eligible for reperfusion therapy, FLAIR vascular
      hyperintensity extent was associated with good collaterals, as assessed by the
      pretreatment hypoperfusion intensity ratio. The ASPECTS assessment of FLAIR
      vascular hyperintensities could be used to rapidly identify patients more likely
      to benefit from reperfusion therapy.

PMID- 29074636
TI  - Heinz First to Routinely Catheterize Carotid and Vertebral Arteries in America.

PMID- 29074637
TI  - MR Elastography Analysis of Glioma Stiffness and IDH1-Mutation Status.
AB  - BACKGROUND AND PURPOSE: Our aim was to noninvasively evaluate gliomas with MR
      elastography to characterize the relationship of tumor stiffness with tumor grade
      and mutations in the isocitrate dehydrogenase 1 (IDH1) gene. MATERIALS AND
      METHODS: Tumor stiffness properties were prospectively quantified in 18 patients
      (mean age, 42 years; 6 women) with histologically proved gliomas using MR
      elastography from 2014 to 2016. Images were acquired on a 3T MR imaging unit with
      a vibration frequency of 60 Hz. Tumor stiffness was compared with unaffected
      contralateral white matter, across tumor grade, and by IDH1-mutation status. The
      performance of the use of tumor stiffness to predict tumor grade and IDH1
      mutation was evaluated with the Wilcoxon rank sum, 1-way ANOVA, and Tukey-Kramer
      tests. RESULTS: Gliomas were softer than healthy brain parenchyma, 2.2 kPa
      compared with 3.3 kPa (P < .001), with grade IV tumors softer than grade II.
      Tumors with an IDH1 mutation were significantly stiffer than those with wild type
      IDH1, 2.5 kPa versus 1.6 kPa, respectively (P = .007). CONCLUSIONS: MR
      elastography demonstrated that not only were gliomas softer than normal brain but
      the degree of softening was directly correlated with tumor grade and IDH1
      mutation status. Noninvasive determination of tumor grade and IDH1 mutation may
      result in improved stratification of patients for different treatment options and
      the evaluation of novel therapeutics. This work reports on the emerging field of
      "mechanogenomics": the identification of genetic features such as IDH1 mutation
      using intrinsic biomechanical information.

PMID- 29074638
TI  - Association between Carotid Plaque Features on CTA and Cerebrovascular Ischemia:
      A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: CTA is a widely available imaging examination that may allow the
      evaluation of high-risk carotid plaque features. PURPOSE: Our aim was to evaluate
      the association between specific carotid plaque features on CTA and ipsilateral
      cerebrovascular ischemia. DATA SOURCES: We performed a systematic review of Ovid
      MEDLINE, Ovid Embase, Scopus, and the Cochrane Library from inception to March
      2016 for articles that evaluated the relationship between CTA-detected carotid
      plaque features and ischemic events, defined as ipsilateral ischemic stroke or
      transient ischemic attack. STUDY SELECTION: Sixteen studies were ultimately
      included after screening 12,557. DATA ANALYSIS: Two readers recorded data from
      each study and assessed the study quality with all disagreements resolved by a
      third reader. A random-effects OR was used to evaluate the association between
      cerebrovascular ischemia and each of the evaluated plaque features. DATA
      SYNTHESIS: We found significant positive relationships with cerebrovascular
      ischemia for the presence of soft plaque (OR, 2.9; 95% CI, 1.4-6.0), plaque
      ulceration (OR, 2.2; 95% CI, 1.4-3.4), and increased common carotid artery wall
      thickness (OR, 6.2; 95% CI, 2.5-15.6). We found a significant negative
      relationship between calcified plaque and ipsilateral ischemia (OR, 0.5; 95% CI,
      0.4-0.7). LIMITATIONS: We found heterogeneity in the existing literature
      secondary to lack of standardized plaque features and clinical definitions.
      CONCLUSIONS: Soft plaque, plaque ulceration, and increased common carotid artery
      wall thickness on CTA are associated with ipsilateral cerebrovascular ischemia,
      while calcified plaque is negatively associated with downstream ischemic events.

PMID- 29074639
TI  - Competing interests in journal editors.

PMID- 29074641
TI  - New approach is urged for Scottish NHS.

PMID- 29074642
TI  - Haemorrhagic bullae in the oral mucosa with gingival bleeding.

PMID- 29074643
TI  - The Involvement of Adolescents With Chronic Health Conditions in Medical
      Education: An Exploratory Qualitative Study.
AB  - OBJECTIVES: In this study, we explored the involvement of adolescents with
      chronic health conditions in medical education. We focused specifically on
      adolescents' desired level of involvement in the education of medical students
      and residents, strategies for involving them in it, and topics on which they
      would feel comfortable educating these learners. METHODS: We used a community
      based participatory research approach and qualitative one-on-one semistructured
      interviews. Adolescents (ages 13-18) with chronic health conditions lasting >3
      months who were admitted on inpatient wards and were well enough to participate
      in an interview were eligible. Two investigators analyzed the interview
      transcripts to identify common categories across the interview data. RESULTS: A
      total of 17 adolescents participated. Data analysis revealed that adolescents
      want to be regularly involved in medical education, compensated in some way for
      their time and effort, and receive support and oversight in their activities.
      Adolescents discussed the following 5 strategies for involving them in the
      education of medical students and residents: face-to-face presentations,
      shadowing and mentoring, videos, handouts and books, and assessment feedback.
      Adolescents want to educate learners on their experiences and coping strategies
      as well as on how to interact and develop rapport with adolescents. CONCLUSIONS:
      The adolescents with chronic health conditions who participated in this study
      want to be actively involved in medical education and can provide innovative
      insights and strategies for doing so. However, future researchers need to explore
      the benefits and limitations of such involvement.

PMID- 29074640
TI  - TSPO mutations in rats and a human polymorphism impair the rate of steroid
      synthesis.
AB  - The 18 kDa translocator protein (TSPO) is a ubiquitous conserved outer
      mitochondrial membrane protein implicated in numerous cell and tissue functions,
      including steroid hormone biosynthesis, respiration, cell proliferation, and
      apoptosis. TSPO binds with high affinity to cholesterol and numerous compounds,
      is expressed at high levels in steroid-synthesizing tissues, and mediates
      cholesterol import into mitochondria, which is the rate-limiting step in steroid
      formation. In humans, the rs6971 polymorphism on the TSPO gene leads to an amino
      acid substitution in the fifth transmembrane loop of the protein, which is where
      the cholesterol-binding domain of TSPO is located, and this polymorphism has been
      associated with anxiety-related disorders. However, recent knockout mouse models
      have provided inconsistent conclusions of whether TSPO is directly involved in
      steroid synthesis. In this report, we show that TSPO deletion mutations in rat
      and its corresponding rs6971 polymorphism in humans alter adrenocorticotropic
      hormone-induced plasma corticosteroid concentrations. Rat tissues examined show
      increased cholesteryl ester accumulation, and neurosteroid formation was
      undetectable in homozygous rats. These results also support a role for TSPO
      ligands in diseases with steroid-dependent stress and anxiety elements.

PMID- 29074645
TI  - Complete Genome Sequence of Alteromonas Virus vB_AspP-H4/4.
AB  - Alteromonas virus vB_AspP-H4/4 is a member of the Podoviridae family and was
      isolated from North Sea water in the 1970s. The complete double-stranded DNA
      genome has 47,631 bp with 49 predicted genes.

PMID- 29074644
TI  - Extracellular Signal-Regulated Kinase 1/2 Regulates Mouse Kidney Injury Molecule
      1 Expression Physiologically and Following Ischemic and Septic Renal Injury.
AB  - The upregulation of kidney injury molecule-1 (KIM-1) has been extensively studied
      in various renal diseases and following acute injury; however, the initial
      mechanisms controlling KIM-1 expression remain limited. In this study, KIM-1
      expression was examined in mouse renal cell cultures and in two different models
      of acute kidney injury (AKI), ischemia reperfusion (IR)-induced and
      lipopolysaccharide (LPS)-induced sepsis. KIM-1 mRNA increased in both AKI models,
      and pharmacological inhibition of extracellular signal-regulated kinase 1/2
      (ERK1/2) signaling attenuated injury-induced KIM-1 expression in the renal
      cortex. Toll-like receptor 4 knockout (TLR4KO) mice exhibited reduced ERK1/2
      phosphorylation and attenuated KIM-1 mRNA after LPS exposure. TLR4KO mice were
      not protected from IR-induced ERK1/2 phosphorylation and upregulation of KIM-1
      mRNA. Following renal IR injury, phosphorylation of signal transducer and
      activator of transcription 3 (STAT3) at serine 727 and tyrosine 705 increased
      downstream from ERK1/2 activation. Because phosphorylated STAT3 is a
      transcriptional upregulator of KIM-1 and inhibition of ERK1/2 attenuated
      increases in STAT3 phosphorylation, we suggest an ERK1/2-STAT3-KIM-1 pathway
      following renal injury. Finally, ERK1/2 inhibition in naive mice decreased KIM-1
      mRNA and nuclear STAT3 phosphorylation in the cortex, indicating homeostatic
      regulation of KIM-1. These findings reveal renal ERK1/2 as an important initial
      regulator of KIM-1 expression in IR and septic AKI and at a physiologic
      level.Visual Abstract.Proposed mechanism of IR, LPS, and ROS-induced renal damage
      that initiates ERK1/2 and STAT3 phosphorylation. STAT3 then binds to the KIM-1
      promoter and increases KIM-1 mRNA. By preventing ERK1/2 phosphorylation following
      renal injury, STAT3 phosphorylation is decreased, leading to less phosphorylated
      STAT3 within the nucleus, and subsequently less KIM-1 mRNA increases post injury.

PMID- 29074646
TI  - Complete Genome Sequence of Mesorhizobium sophorae ICMP 19535T, a Highly
      Specific, Nitrogen-Fixing Symbiont of New Zealand Endemic Sophora spp.
AB  - We report here the complete genome sequence of Mesorhizobium sophorae ICMP 19535T
      This strain was isolated from Sophora microphylla root nodules and can nodulate
      and fix nitrogen with this host and also with Sophora prostrata, Sophora
      longicarinata, and Clianthus puniceus The genome consists of 8.05 Mb.

PMID- 29074647
TI  - Draft Genome Sequence of the Wood-Degrading Ascomycete Kretzschmaria deusta DSM
      104547.
AB  - We report here the draft genome of Kretzschmaria (Ustulina) deusta, an
      ascomycetous fungus that colonizes and substantially degrades hardwood and can
      infest living broad-leaved trees. The genome was assembled into 858 contigs, with
      a total size of 46.5 Mb, and 11,074 protein-coding genes were predicted.

PMID- 29074648
TI  - Draft Nuclear Genome Sequence of the Halophilic and Beta-Carotene-Accumulating
      Green Alga Dunaliella salina Strain CCAP19/18.
AB  - The halotolerant alga Dunaliella salina is a model for stress tolerance and is
      used commercially for production of beta-carotene (=pro-vitamin A). The presented
      draft genome of the genuine strain CCAP19/18 will allow investigations into
      metabolic processes involved in regulation of stress responses, including
      carotenogenesis and adaptations to life in high-salinity environments.

PMID- 29074649
TI  - Complete Genome Sequence of West Nile Virus (WNV) from the First Human Case of
      Neuroinvasive WNV Infection in Cyprus.
AB  - We report here the complete genome sequence of a West Nile virus (WNV) strain
      from the first laboratory-confirmed human case of neuroinvasive WNV infection in
      Cyprus. Phylogenetic analysis showed that this WNV strain grouped clearly into
      genetic lineage 1, clade 1a, cluster 2.

PMID- 29074650
TI  - Correction for Bertoni-Mann et al., "Draft Genome Sequence of Phytopathogenic
      Fungus Fusarium proliferatum CF-295141, Isolated from Pinus sylvestris".

PMID- 29074651
TI  - Full-Genome Characterization of Simian T-Cell Leukemia Virus Type 1 Subtype b
      from a Wild-Born Captive Gorilla gorilla gorilla with T-Cell Lymphoma.
AB  - There are four lineages of primate T-cell lymphocytic viruses (human T-cell
      lymphocytic virus [HTLV]/simian T-cell lymphocytic virus [STLV]), which are
      further divided into subtypes. To date, there is only one full-length HTLV-1
      subtype b genome available. Here, we report the genome of a new STLV-1 subtype b
      from a 43-year-old male gorilla with T-cell lymphoma.

PMID- 29074652
TI  - Complete Genome Sequence of the Temperate Klebsiella pneumoniae Phage KPP5665-2.
AB  - We describe here the genome sequence of the novel temperate Klebsiella pneumoniae
      phage KPP5665-2 isolated from a Klebsiella pneumoniae strain recovered from milk
      in Germany in 2016. The phage exhibited a narrow host range and a siphoviridal
      morphology. KPP5665-2-related prophage sequences were detected in whole-genome
      sequencing (WGS) data of various Klebsiella species isolates.

PMID- 29074653
TI  - Draft Genome Assembly of a Wolbachia Endosymbiont of Plutella australiana.
AB  - Wolbachia spp. are endosymbiotic bacteria that infect around 50% of arthropods
      and cause a broad range of effects, including manipulating host reproduction.
      Here, we present the annotated draft genome assembly of Wolbachia strain wAus,
      which infects Plutella australiana, a cryptic ally of the major Brassica pest
      Plutella xylostella (diamondback moth).

PMID- 29074654
TI  - Complete Genome Sequence of the Circulatory Foot-and-Mouth Disease Virus Serotype
      Asia1 in Bangladesh.
AB  - The complete genome sequence of foot-and-mouth disease virus (FMDV) serotype
      Asia1 isolated from Bangladesh is reported here. Genome analysis revealed amino
      acid substitutions in the VP1 antigenic region and deletions in both the 5' and
      3' untranslated regions (UTRs) compared to the genome of the existing vaccine
      strain (GenBank accession no. AY304994).

PMID- 29074655
TI  - Complete Coding Genome Sequences of Uncommon GII.8 Sapovirus Strains Identified
      in Diarrhea Samples Collected from Peruvian Children.
AB  - We report here two complete coding genome sequences of novel genotype GII.8
      sapovirus strains identified in diarrhea samples collected from two Peruvian
      children. The complete coding genome sequences of both GII.8 variants were
      determined using the Sanger sequencing method.

PMID- 29074657
TI  - Genome Sequence of Kocuria polaris Strain CD08_4, an Isolate from the Duodenal
      Mucosa of a Celiac Disease Patient.
AB  - We report here the 3.8-Mb genome sequence of Kocuria polaris strain CD08_4, an
      isolate from the duodenal mucosa of a celiac disease patient. The genome consists
      of specific virulence determinant genes, antibiotic resistance genes, genes for
      coping with oxidative stress, and genes responsible for iron acquisition and
      metabolism, suggestive of its pathogenic attributes.

PMID- 29074656
TI  - Draft Genome Sequence of Pseudomonas fluorescens Strain ITEM 17298, Associated
      with Cheese Spoilage.
AB  - Pseudomonas fluorescens is a genetically and phenotypically heterogeneous species
      that is often reported as a spoiler of fresh foods, but it has recently been
      implicated in clinical infection. In this study, we sequenced the genome of P.
      fluorescens strain ITEM 17298, isolated from mozzarella cheese and able to cause
      several alterations under cold storage.

PMID- 29074658
TI  - Complete Genome Sequence of Bacillus subtilis Strain CGMCC 12426, an Efficient
      Poly-gamma-Glutamate Producer.
AB  - Bacillus subtilis CGMCC 12426 is an efficient producer of poly-gamma-glutamate
      with regular stereochemistry. Here, the complete genome sequence of B. subtilis
      CGMCC 12426 is presented, which may facilitate the design of rational strategies
      for further strain improvements with industrial potential.

PMID- 29074659
TI  - Complete Genome Sequence of Eubacterium hallii Strain L2-7.
AB  - The complete genome sequence of Eubacterium hallii strain L2-7 is reported here.
      This intestinal strain produces butyrate from glucose as well as lactate when
      acetate is provided in the growth medium. In addition, strain L2-7 has been shown
      to improve insulin sensitivity in db/db mice, indicating its application
      potential.

PMID- 29074660
TI  - Genome Sequence of Geobacillus stearothermophilus DSM 458, an Antimicrobial
      Producing Thermophilic Bacterium, Isolated from a Sugar Beet Factory.
AB  - This paper reports the full genome sequence of the antimicrobial-producing
      bacterium Geobacillus stearothermophilus DSM 458, isolated in a sugar beet
      factory in Austria. In silico analysis reveals the presence of a number of novel
      bacteriocin biosynthetic genes.

PMID- 29074661
TI  - Genomic Sequences of Epizootic Hemorrhagic Disease Viruses Isolated from Florida
      White-Tailed Deer.
AB  - Epizootic hemorrhagic disease virus (EHDV) serotypes 1 and 2 were isolated from
      Florida white-tailed deer in 2015 and 2016, respectively, and their genomes were
      completely sequenced. To our knowledge, these are the first full genome sequences
      for EHDV-1 and -2 from Florida.

PMID- 29074663
TI  - Draft Genome Sequence of Arsenic-Resistant Microbacterium sp. Strain SZ1 Isolated
      from Arsenic-Bearing Gold Ores.
AB  - Microbacterium sp. strain SZ1 isolated from gold ores of a Malaysia gold mine was
      found to be highly resistant to arsenic. Here, we report the draft genome
      sequence of SZ1, which may provide further insights into understanding its
      arsenic resistance mechanism. In this draft genome, a complete set of ars operons
      and two additional scattered ars genes were encoded.

PMID- 29074662
TI  - Complete Genome Sequences of Cluster A Mycobacteriophages BobSwaget, Fred313,
      KADY, Lokk, MyraDee, Stagni, and StepMih.
AB  - Seven mycobacteriophages from distinct geographical locations were isolated,
      using Mycobacterium smegmatis mc2155 as the host, and then purified and
      sequenced. All of the genomes are related to cluster A mycobacteriophages,
      BobSwaget and Lokk in subcluster A2; Fred313, KADY, Stagni, and StepMih in
      subcluster A3; and MyraDee in subcluster A18, the first phage to be assigned to
      that subcluster.

PMID- 29074665
TI  - Draft Genome Sequence of Rhizoctonia solani Anastomosis Group 1 Subgroup 1A
      Strain 1802/KB Isolated from Rice.
AB  - Sheath blight, caused by Rhizoctonia solani anastomosis group 1 subgroup 1A (AG1
      1A), is one of the most devastating rice diseases worldwide. Here, we report the
      draft genome sequence of R. solani AG1-1A strain 1802/KB isolated from a popular
      Malaysian rice variety. To the best of our knowledge, this is the second reported
      representative genome from AG1-1A.

PMID- 29074664
TI  - Complete Genome Sequence of Kluyvera intestini sp. nov., Isolated from the
      Stomach of a Patient with Gastric Cancer.
AB  - We report here an update to the draft genome sequence of Kluyvera intestini sp.
      nov. strain GT-16, generated using MinION long-read sequencing technology. The
      complete genome sequence of the human-derived strain GT-16 measured 5,768,848 bp.
      An improved high-quality complete genome sequence provides insights into the
      mobility potential of resistance genes in this species.

PMID- 29074666
TI  - Genome Sequence of the Lager-Brewing Yeast Saccharomyces sp. Strain M14, Used in
      the High-Gravity Brewing Industry in China.
AB  - Lager-brewing yeasts are mainly used for the production of lager beers. Illumina
      and PacBio-based sequence analyses revealed an approximate genome size of 22.8
      Mb, with a GC content of 38.98%, for the Chinese lager-brewing yeast
      Saccharomyces sp. strain M14. Based on ab initio prediction, 9,970 coding genes
      were annotated.

PMID- 29074667
TI  - Whole-Genome Sequence of the Fruiting Myxobacterium Cystobacter fuscus DSM 52655.
AB  - Among myxobacteria, the genus Cystobacter is known not only for fruiting body
      formation but also for formation of secondary metabolites, such as cystobactamids
      and cystothiazols. Here, we present the complete genome sequence of the
      Cystobacter fuscus strain DSM 52655, which comprises 12,349,744 bp and 9,836
      putative protein-coding sequences.

PMID- 29074668
TI  - Draft Whole-Genome Sequence of Psychrotrophic Arthrobacter sp. Strain 7749,
      Isolated from Antarctic Marine Sediments with Applications in Enantioselective
      Alcohol Oxidation.
AB  - Here, we report the 4.12-Mb draft genome sequence of Arthrobacter sp. strain
      7749, isolated from marine sediment samples of the Antarctic Peninsula, using
      enriched medium with (RS)-1-(4-phenyl)-ethanol as a carbon source. This genome
      sequence will provide relevant information for applications in enantioselective
      alcohol oxidation to improve industrial catalytic processes.

PMID- 29074670
TI  - Complete Genome Sequence of Desulfovibrio desulfuricans Strain G11, a Model
      Sulfate-Reducing, Hydrogenotrophic, and Syntrophic Partner Organism.
AB  - Here, we report the draft genome of the Gram-negative, sulfate-reducing bacterium
      Desulfovibrio desulfuricans strain G11. Isolated from a rumen fluid enrichment,
      this culture has been a model syntrophic partner due to its metabolic
      flexibility. The assembly yielded a single circular chromosome of 3,414,943 bp
      and a 57% G+C content.

PMID- 29074669
TI  - Draft Genome Sequence of Rhodococcus enclensis 23b-28, a Model Strain Isolated
      from Cloud Water.
AB  - The whole genome of Rhodococcus enclensis 23b-28, a bacterial strain isolated
      from cloud water, was sequenced. This microorganism is equipped with genes able
      to degrade aromatic compounds and could thus play a role in complex organic
      matter decomposition in cloud water.

PMID- 29074671
TI  - Complete Genome Sequence of Bacillus paralicheniformis 14DA11, Exhibiting
      Resistance to Clindamycin and Erythromycin.
AB  - Bacillus paralicheniformis 14DA11, exhibiting resistance to clindamycin and
      erythromycin, was isolated from a Korean fermented soybean food product. The
      complete genome of strain 14DA11 includes genes that potentially contribute to
      the antibiotic resistance.

PMID- 29074672
TI  - Complete Genome Sequence of the Hippuricase-Positive Campylobacter avium Type
      Strain LMG 24591.
AB  - Campylobacter avium is a thermotolerant Campylobacter species that has been
      isolated from poultry. C. avium was also the second hippuricase-positive species
      to be identified within Campylobacter Here, we present the genome sequence of the
      C. avium type strain LMG 24591 (=CCUG 56292T), isolated in 2006 from a broiler
      chicken in Italy.

PMID- 29074673
TI  - Draft Genome Sequence of the Fruiting Myxobacterium Nannocystis exedens DSM 71.
AB  - In response to starvation, members of the order Myxococcales form morphologically
      very different fruiting bodies. To determine whether fruiting myxobacteria share
      a common genetic program that leads to fruiting body formation, we sequenced and
      assembled the genome of Nannocystis exedens DSM 71 as two contigs with a total GC
      content of 72%.

PMID- 29074674
TI  - Draft Genome Sequences of Two Brazilian Cyanobacterial Strains of
      Cylindrospermopsis raciborskii: Differences in Membrane Transporters, Saxitoxin
      Production, and Antioxidant Activities.
AB  - We report here the draft genome sequences of two Brazilian strains of
      Cylindrospermopsis raciborskii, a saxitoxin-producer (CYRF) and a non-saxitoxin
      producer (CYLP), with each strain comprising one assembled scaffold. We revealed
      differences in the compositions of gene members coding for membrane transporters
      and antioxidant activities between the strains.

PMID- 29074675
TI  - Future Tense.

PMID- 29074676
TI  - Interface medicine: a new generalism for the NHS.

PMID- 29074677
TI  - Decision support for diagnosis should become routine in 21st century primary
      care.

PMID- 29074678
TI  - Sustainability or transformation? Without additional funding, STPs are unlikely
      to deliver both.

PMID- 29074679
TI  - Developing middle-ground research to support primary care transformation.

PMID- 29074680
TI  - Future care for older people in general practice: paradigm shifts are needed.

PMID- 29074681
TI  - View from the trenches.

PMID- 29074683
TI  - Authors' response.

PMID- 29074682
TI  - Prescribed drug dependence services for long-term BZD use: treating the problem
      while ignoring its causes.

PMID- 29074684
TI  - NHS is not all that bad.

PMID- 29074685
TI  - Pharmacists' role in primary care.

PMID- 29074686
TI  - Viewpoint: Be the best you.

PMID- 29074687
TI  - Access to medical records for assisted death: clarifying the guidance.

PMID- 29074689
TI  - The lost sheep.

PMID- 29074688
TI  - My locum life: 20 years trying to make myself obsolete.

PMID- 29074690
TI  - Yonder: Case finding, HIV testing, trainee inductions, and waiting rooms.

PMID- 29074691
TI  - Bad Medicine: For the few, not the many.

PMID- 29074692
TI  - RCGP Research Paper of the Year 2016: how the winning papers are so relevant to
      clinical practice.

PMID- 29074693
TI  - Books: The Future of the Professions: How Technology Will Transform the Work of
      Human Experts: Existential Angst in a Digital Age.

PMID- 29074694
TI  - Are you OK?

PMID- 29074695
TI  - The future role of receptionists in primary care.

PMID- 29074696
TI  - Sustainability and Transformation Plans: occupational therapists and
      physiotherapists can support GPs.

PMID- 29074697
TI  - Young carers in the NHS.

PMID- 29074698
TI  - Perioperative resources for GPs.

PMID- 29074700
TI  - Northern Ireland trainees are well supported and supervised, GMC finds.

PMID- 29074699
TI  - Fractional exhaled nitric oxide monitoring in paediatric asthma management.

PMID- 29074701
TI  - Context-dependent chemosensory signaling, aggression and neural activation
      patterns in gravid female African cichlid fish.
AB  - Social animals must constantly assess their environment to make appropriate
      behavioral decisions. The use of various sensory modalities is imperative in this
      process and it is hypothesized that the highly conserved brain nuclei comprising
      the social decision-making network (SDMN) integrates social information with an
      animal's internal state to elicit behavioral responses. Here, we used the highly
      social African cichlid fish, Astatotilapia burtoni, to investigate whether
      reproductively receptive (gravid) females show contextual chemosensory signaling,
      social behaviors and neural activation patterns within the SDMN. We exposed
      gravid females to different social contexts: (1) dominant male (inter-sexual
      reproductive); (2) mouth brooding (non-receptive) female; (3) gravid female
      (intra-sexual aggressive); (4) juvenile fish (low social salience); and (5) empty
      compartment (control). By injecting females with a blue dye to visualize urine
      pulses, we found that gravid females show context-dependent urination, exhibiting
      higher urination rates in the presence of dominant males (reproductive context)
      and mouth brooding females (aggressive contexts). Further, gravid females show
      contextual aggression with increased aggressive displays toward mouth brooding
      females compared with other gravid females. Using in situ hybridization to
      quantify cells expressing the immediate early gene cfos as a measure of neural
      activation, we also show that certain regions of the SDMN in gravid females are
      differentially activated after exposure to high compared with low social salience
      contexts. Coupled with previous reports, these results demonstrate true
      chemosensory communication in both sexes of a single fish species, as well as
      reveal the neural substrates mediating intra- and inter-sexual social behaviors
      in females.

PMID- 29074702
TI  - Respiratory consequences of targeted losses of Hoxa5 gene function in mice.
AB  - Fetal development of the respiratory tract and diaphragm requires strict
      coordination between genetically controlled signals and mechanical forces
      produced by the neural network that generates breathing. HOXA5, which is
      expressed in the mesenchyme of the trachea, lung and diaphragm, and in phrenic
      motor neurons, is a key transcription factor regulating lung development and
      function. Consequently, most Hoxa5-/- mutants die at birth from respiratory
      failure. However, the extensive effect of the null mutation makes it difficult to
      identify the origins of respiratory dysfunction in newborns. To address the
      physiological impact of Hoxa5 tissue-specific roles, we used conditional gene
      targeting with the Dermo1Cre and Olig2Cre mouse lines to produce specific Hoxa5
      deletions in the mesenchyme and motor neurons, respectively. Hoxa5 expression in
      the mesenchyme is critical for trachea development, whereas its expression in
      phrenic motor neurons is essential for diaphragm formation. Breathing
      measurements in adult mice with whole-body plethysmography demonstrated that, at
      rest, only the motor neuron deletion affects respiration, resulting in higher
      breathing frequency and decreased tidal volume. But subsequent exposure to a
      moderate hypoxic challenge (FiO2 =0.12; 10 min) revealed that both mutant mice
      hyperventilate more than controls. Hoxa5flox/flox;Dermo1+/Cre mice showed
      augmented tidal volume while Hoxa5flox/flox;Olig2+/Cre mice had the largest
      increase in breathing frequency. No significant differences were observed between
      medulla-spinal cord preparations from E18.5 control and Hoxa5flox/flox;Olig2+/Cre
      mouse embryos that could support a role for Hoxa5 in fetal inspiratory motor
      command. According to our data, Hoxa5 expression in the mesenchyme and phrenic
      motor neurons controls distinct aspects of respiratory development.

PMID- 29074703
TI  - Durophagous biting in sea otters (Enhydra lutris) differs kinematically from
      raptorial biting of other marine mammals.
AB  - Sea otters represent an interesting model for studies of mammalian feeding
      evolution. Although they are marine mammals, sea otters returned to the sea
      relatively recently and feed at the surface. Therefore, they represent a
      transitional stage of aquatic adaptation. Currently no feeding performance
      studies of sea otters have been conducted. The main objective of this study was
      to characterize the feeding kinematic profile in sea otters. It was hypothesized
      that sea otters would exhibit a terrestrial feeding behavior and that they
      forcefully crush hard prey at large gapes. As a result, biting kinematics would
      be congruent with biting behavior reported for their terrestrial ancestors, thus
      providing additional evidence that raptorial biting is a conserved behavior even
      in recently aquatic mammals. Sea otters consistently used a durophagous raptorial
      biting mode characterized by large gapes, large gape angles and lack of lateral
      gape occlusion. The shorter skulls and mandibles of sea otters, along with
      increased mechanical advantages of the masseter and increased bite force, form a
      repertoire of functional traits for durophagy. Here we consider durophagy to be a
      specialized raptorial biting feeding mode. A comparison of feeding kinematics of
      wild versus captive sea otters showed no significant differences in lateral
      kinematic profiles, and only minor differences in three frontal kinematic
      profiles, which included a slower maximum opening gape velocity, a slower maximum
      gape opening velocity, and a slower maximum closing gape velocity in captive sea
      otters. Data indicate functional innovations for producing large bite forces at
      wide gape and gape angles.

PMID- 29074704
TI  - Characterizing the distribution of steroid sulfatase during embryonic
      development: when and where might metabolites of maternal steroids be
      reactivated?
AB  - All vertebrate embryos are exposed to maternally derived steroids during
      development. In placental vertebrates, metabolism of maternal steroids by the
      placenta modulates embryonic exposure, but how exposure is regulated in oviparous
      vertebrates is less clear. Recent work in oviparous vertebrates has demonstrated
      that steroids are not static molecules, as they can be converted to more polar
      steroid sulfates by sulfotransferase enzymes. Importantly, these steroid sulfates
      can be converted back to the parent compound by the enzyme steroid sulfatase
      (STS). We investigated when and where STS was present during embryonic
      development in the red-eared slider turtle, Trachemys scripta We report that STS
      is present during all stages of development and in all tissues we examined. We
      conclude that STS activity may be particularly important for regulating maternal
      steroid exposure in oviparous vertebrates.

PMID- 29074706
TI  - Aurora A activation in mitosis promoted by BuGZ.
AB  - Protein phase separation or coacervation has emerged as a potential mechanism to
      regulate biological functions. We have shown that coacervation of a mostly
      unstructured protein, BuGZ, promotes assembly of spindle and its matrix. BuGZ in
      the spindle matrix binds and concentrates tubulin to promote microtubule (MT)
      assembly. It remains unclear, however, whether BuGZ could regulate additional
      proteins to promote spindle assembly. In this study, we report that BuGZ promotes
      Aurora A (AurA) activation in vitro. Depletion of BuGZ in cells reduces the
      amount of phosphorylated AurA on spindle MTs. BuGZ also enhances MCAK
      phosphorylation. The two zinc fingers in BuGZ directly bind to the kinase domain
      of AurA, which allows AurA to incorporate into the coacervates formed by BuGZ in
      vitro. Importantly, mutant BuGZ that disrupts the coacervation activity in vitro
      fails to promote AurA phosphorylation in Xenopus laevis egg extracts. These
      results suggest that BuGZ coacervation promotes AurA activation in mitosis.

PMID- 29074708
TI  - Wearable physiological sensors and real-time algorithms for detection of acute
      mountain sickness.
AB  - This is a minireview of potential wearable physiological sensors and algorithms
      (process and equations) for detection of acute mountain sickness (AMS). Given the
      emerging status of this effort, the focus of the review is on the current
      clinical assessment of AMS, known risk factors (environmental, demographic, and
      physiological), and current understanding of AMS pathophysiology. Studies that
      have examined a range of physiological variables to develop AMS prediction and/or
      detection algorithms are reviewed to provide insight and potential technological
      roadmaps for future development of real-time physiological sensors and algorithms
      to detect AMS. Given the lack of signs and nonspecific symptoms associated with
      AMS, development of wearable physiological sensors and embedded algorithms to
      predict in the near term or detect established AMS will be challenging. Prior
      work using [Formula: see text], HR, or HRv has not provided the sensitivity and
      specificity for useful application to predict or detect AMS. Rather than using
      spot checks as most prior studies have, wearable systems that continuously
      measure SpO2 and HR are commercially available. Employing other statistical
      modeling approaches such as general linear and logistic mixed models or time
      series analysis to these continuously measured variables is the most promising
      approach for developing algorithms that are sensitive and specific for
      physiological prediction or detection of AMS.

PMID- 29074705
TI  - Regulation of reproduction and longevity by nutrient-sensing pathways.
AB  - Nutrients are necessary for life, as they are a crucial requirement for
      biological processes including reproduction, somatic growth, and tissue
      maintenance. Therefore, signaling systems involved in detecting and interpreting
      nutrient or energy levels-most notably, the insulin/insulin-like growth factor 1
      (IGF-1) signaling pathway, mechanistic target of rapamycin (mTOR), and adenosine
      monophosphate-activated protein kinase (AMPK)-play important roles in regulating
      physiological decisions to reproduce, grow, and age. In this review, we discuss
      the connections between reproductive senescence and somatic aging and give an
      overview of the involvement of nutrient-sensing pathways in controlling both
      reproductive function and lifespan. Although the molecular mechanisms that affect
      these processes can be influenced by distinct tissue-, temporal-, and pathway
      specific signaling events, the progression of reproductive aging and somatic
      aging is systemically coordinated by integrated nutrient-sensing signaling
      pathways regulating somatic tissue maintenance in conjunction with reproductive
      capacity.

PMID- 29074709
TI  - A time-course evaluation of inflammatory and oxidative markers following high
      intensity exercise in horses: a pilot study.
AB  - Exercise is a physiological stress resulting in reactive oxygen species and
      inflammatory mediators, the accumulation of which are thought to contribute to
      degenerative articular diseases. The horse is of particular interest in this
      regard as equine athletes are frequently exposed to repetitive bouts of high
      intensity exercise. The purpose of this study was to provide a detailed
      description of the response of articular and systemic oxidative and inflammatory
      biomarkers following high-intensity, exhaustive exercise in horses. A group of
      horses (Ex) underwent repeated bouts of high-intensity exercise, at a target
      heart rate of 180 beats/min, until voluntary exhaustion. Baseline plasma and
      synovial fluid (SF) samples were taken 24 h before exercise and then at 0.5, 1,
      2, 4, 8, and 24 h following exercise cessation. This time course was repeated in
      a group of nonexercised control horses (Co). Plasma and SF samples were analyzed
      for prostaglandin E2 (PGE2), nitric oxide (NO), total antioxidant status (TAS),
      and glycosaminoglycans (GAG). The Ex group had significantly higher plasma NO at
      0.5, 1, and 2 h; and higher plasma PGE2 at 0.5 and 1 h compared with Co. SF PGE2
      and GAG were also higher in Ex horses at 8 h compared with Co. It is concluded
      that high-intensity exercise in horses results in a rapid increase in systemic
      oxidative and inflammatory markers from 0.5 to 2 h after exercise, which is
      followed by local articular inflammation and cartilage turnover at 8 h
      postexercise. NEW & NOTEWORTHY In horses, the influence of exercise systemically
      and within the articular space remains unclear and requires further detailed
      characterization. In this study, we identify that an acute bout of high-intensity
      exercise in horses induces systemic inflammation and oxidative stress within 30
      min of exercise cessation, which lasts for ~2 h. Articular inflammation and
      cartilage turnover were also be observed within the equine carpal joint 8 h
      following exercise completion.

PMID- 29074710
TI  - Muscle damage produced by isometric contractions in human elbow flexors.
AB  - Isometric exercise is often prescribed during rehabilitation from injury to
      maintain muscle condition and prevent disuse atrophy. However, such exercise can
      lead to muscle soreness and damage. Here we investigate which parameters of
      isometric contractions are responsible for the damage. Bouts of 30 repetitions of
      maximum voluntary contractions of elbow flexors in 38 subjects were carried out
      and peak force, soreness, and tenderness were measured before the exercise,
      immediately afterwards, at 2 h, and at 24 h postexercise. When one arm was held
      near the optimum angle for force generation (90 degrees ), the force it produced
      was greater by 28% than by the other arm held at a longer length (155 degrees ).
      However, despite the smaller contraction forces of the muscle held at the longer
      length, after the exercise it exhibited a greater fall in force that persisted
      out to 24 h (20% fall) and more delayed soreness than the muscle exercised at 90
      degrees  (7% fall at 24 h). The result indicates a length dependence of the
      damage process for isometric contractions at maximum effort. In four additional
      experiments, evidence was provided that the damage occurred during the plateau of
      the contraction and not the rising or relaxation phases. The damage had a prompt
      onset and was cumulative, continuing for the duration of the contraction. We
      interpret our findings in terms of the nonuniform lengthening of sarcomeres
      during the plateau of the contractions and conclude that muscle damage from
      isometric exercise is minimized if carried out at lengths below the optimum,
      using half-maximum or smaller contractions. NEW & NOTEWORTHY Isometric exercise,
      where muscle contracts while the limb is held fixed, is often possible for
      individuals rehabilitating from injury and can help maintain muscle condition.
      Such exercise has been reported to cause some muscle damage and soreness. We
      confirm this and show that to minimize damage, exercising muscles should be held
      at shorter than the optimum length for force and carried out at half-maximum
      effort or less.

PMID- 29074707
TI  - Cyclin B1 is essential for mitosis in mouse embryos, and its nuclear export sets
      the time for mitosis.
AB  - There is remarkable redundancy between the Cyclin-Cdk complexes that comprise the
      cell cycle machinery. None of the mammalian A-, D-, or E-type cyclins are
      required in development until implantation, and only Cdk1 is essential for early
      cell divisions. Cyclin B1 is essential for development, but whether it is
      required for cell division is contentious. Here, we used a novel imaging approach
      to analyze Cyclin B1-null embryos from fertilization onward. We show that Cyclin
      B1-/- embryos arrest in G2 phase after just two divisions. This is the earliest
      arrest of any Cyclin known and places Cyclin B1 with cdk1 as the essential
      regulators of the cell cycle. We reintroduced mutant proteins into this
      genetically null background to determine why Cyclin B1 is constantly exported
      from the nucleus. We found that Cyclin B1 must be exported from the nucleus for
      the cell to prevent premature entry to mitosis, and retaining Cyclin B1-Cdk1 at
      the plasma membrane precludes entry to mitosis.

PMID- 29074711
TI  - Enhanced cerebral perfusion during brief exposures to cyclic intermittent
      hypoxemia.
AB  - Cerebral vasodilation and increased cerebral oxygen extraction help maintain
      cerebral oxygen uptake in the face of hypoxemia. This study examined
      cerebrovascular responses to intermittent hypoxemia in eight healthy men
      breathing 10% O2 for 5 cycles, each 6 min, interspersed with 4 min of room air
      breathing. Hypoxia exposures raised heart rate ( P < 0.01) without altering
      arterial pressure, and increased ventilation ( P < 0.01) by expanding tidal
      volume. Arterial oxygen saturation ([Formula: see text]) and cerebral tissue
      oxygenation ([Formula: see text]) fell ( P < 0.01) less appreciably in the first
      bout (from 97.0 +/- 0.3% and 72.8 +/- 1.6% to 75.5 +/- 0.9% and 54.5 +/- 0.9%,
      respectively) than the fifth bout (from 94.9 +/- 0.4% and 70.8 +/- 1.0% to 66.7
      +/- 2.3% and 49.2 +/- 1.5%, respectively). Flow velocity in the middle cerebral
      artery ( VMCA) and cerebrovascular conductance increased in a sigmoid fashion
      with decreases in [Formula: see text] and [Formula: see text]. These stimulus
      response curves shifted leftward and upward from the first to the fifth hypoxia
      bouts; thus, the centering points fell from 79.2 +/- 1.4 to 74.6 +/- 1.1% ( P =
      0.01) and from 59.8 +/- 1.0 to 56.6 +/- 0.3% ( P = 0.002), and the minimum VMCA
      increased from 54.0 +/- 0.5 to 57.2 +/- 0.5 cm/s ( P = 0.0001) and from 53.9 +/-
      0.5 to 57.1 +/- 0.3 cm/s ( P = 0.0001) for the [Formula: see text]- VMCA and
      [Formula: see text]- VMCA curves, respectively. Cerebral oxygen extraction
      increased from prehypoxia 0.22 +/- 0.01 to 0.25 +/- 0.02 in minute 6 of the first
      hypoxia bout, and remained elevated between 0.25 +/- 0.01 and 0.27 +/- 0.01
      throughout the fifth hypoxia bout. These results demonstrate that cerebral
      vasodilation combined with enhanced cerebral oxygen extraction fully compensated
      for decreased oxygen content during acute, cyclic hypoxemia. NEW & NOTEWORTHY
      Five bouts of 6-min intermittent hypoxia (IH) exposures to 10% O2 progressively
      reduce arterial oxygen saturation ([Formula: see text]) to 67% without causing
      discomfort or distress. Cerebrovascular responses to hypoxemia are dynamically
      reset over the course of a single IH session, such that threshold and saturation
      for cerebral vasodilations occurred at lower [Formula: see text] and cerebral
      tissue oxygenation ([Formula: see text]) during the fifth vs. first hypoxia
      bouts. Cerebral oxygen extraction is augmented during acute hypoxemia, which
      compensates for decreased arterial O2 content.

PMID- 29074713
TI  - Effects of contraction mode and stimulation frequency on electrical stimulation
      induced skeletal muscle hypertrophy.
AB  - We compared the skeletal muscle hypertrophy resulting from isometric (Iso) or
      eccentric (Ecc) electrical stimulation (ES) training with different stimulation
      frequencies. Male Wistar rats were assigned to the Iso and Ecc groups. These were
      divided into three further subgroups that were stimulated at 10 Hz (Iso-10 and
      Ecc-10), 30 Hz (Iso-30 and Ecc-30), or 100 Hz (Iso-100 and Ecc-100). In
      experiment 1, the left plantarflexor muscles were stimulated every other day for
      3 wk. In experiment 2, mammalian target of rapamycin complex 1 (mTORC1) signaling
      was investigated 6 h after one bout of ES. The contralateral right muscle served
      as a control (non-ES). Ecc contractions comprised forced dorsiflexion combined
      with ES. The peak torque and torque-time integral during ES were higher in the
      Ecc group than that in the Iso group in all stimulation frequencies examined. The
      gastrocnemius muscle weight normalized to body weight in ES side was increased
      compared with the non-ES side by 6, 7, and 17% in the Ecc-30, Iso-100, and Ecc
      100 groups, respectively, with a greater gain in Ecc-100 than the Ecc-30 and Iso
      100 groups. The p70S6K (Thr389) phosphorylation level was higher in the Ecc-30
      and -100 than in the Iso-30 and -100 groups, respectively. The peak torque and
      torque-time integral were highly correlated with the magnitude of increase in
      muscle mass and the phosphorylation of p70S6K. These data suggest that ES-induced
      muscle hypertrophy and mTORC1 activity are determined by loading intensity and
      volume during muscle contraction independent of the contraction mode. NEW &
      NOTEWORTHY Eccentric contraction and high-frequency stimulation (HFS) are
      regarded as an effective way to increase muscle mass by electrical stimulation
      (ES) training. However, little is known about whether muscle hypertrophy is
      affected by contraction mode and stimulation frequency in ES training. Here, we
      provide the evidence that muscle hypertrophy and mammalian target of rapamycin
      complex 1 activity are determined by mechanical loading during contraction but
      not on the contraction mode itself, with a greater gain at HFS.

PMID- 29074712
TI  - Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic
      stiffening in old mice.
AB  - Aortic stiffening is a major independent risk factor for cardiovascular diseases,
      cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived
      reactive oxygen species are a key source of arterial oxidative stress, which may
      contribute to arterial stiffening by promoting adverse structural changes
      including collagen overabundance and elastin degradation-and enhancing
      inflammation, but the potential for mitochondria-targeted therapeutic strategies
      to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic
      stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical
      properties [elastic modulus (EM) of collagen and elastin regions], and aortic
      protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming
      normal drinking water (YC and OC) or water containing mitochondria-targeted
      antioxidant MitoQ (250 uM; YMQ and OMQ) for 4 wk. Both baseline and
      postintervention aPWV values were higher in OC vs. YC (post: 482 +/- 21 vs. 420
      +/- 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in
      old mice (OMQ, 426 +/- 20, P < 0.05 vs. OC). MitoQ did not affect age-associated
      increases in aortic collagen-region EM, collagen expression, or proinflammatory
      cytokine expression, but partially attenuated age-associated decreases in elastin
      region EM and elastin expression. Our results demonstrate that MitoQ reverses in
      vivo aortic stiffness in old mice and suggest that mitochondria-targeted
      antioxidants may represent a novel, promising therapeutic strategy for decreasing
      aortic stiffness with primary aging and, possibly, age-related clinical disorders
      in humans. The destiffening effects of MitoQ treatment may be at least partially
      mediated by attenuation/reversal of age-related aortic elastin degradation. NEW &
      NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific
      antioxidant MitoQ in mice completely reverses the age-associated elevation in
      aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening
      effects of MitoQ treatment may be at least partially mediated by attenuation of
      age-related aortic elastin degradation. Our results suggest that mitochondria
      targeted therapeutic strategies may hold promise for decreasing arterial
      stiffening with aging in humans, possibly decreasing the risk of many chronic age
      related clinical disorders.

PMID- 29074714
TI  - Potential for noninvasive assessment of lung inhomogeneity using highly precise,
      highly time-resolved measurements of gas exchange.
AB  - Inhomogeneity in the lung impairs gas exchange and can be an early marker of lung
      disease. We hypothesized that highly precise measurements of gas exchange contain
      sufficient information to quantify many aspects of the inhomogeneity
      noninvasively. Our aim was to explore whether one parameterization of lung
      inhomogeneity could both fit such data and provide reliable parameter estimates.
      A mathematical model of gas exchange in an inhomogeneous lung was developed,
      containing inhomogeneity parameters for compliance, vascular conductance, and
      dead space, all relative to lung volume. Inputs were respiratory flow, cardiac
      output, and the inspiratory and pulmonary arterial gas compositions. Outputs were
      expiratory and pulmonary venous gas compositions. All values were specified every
      10 ms. Some parameters were set to physiologically plausible values. To estimate
      the remaining unknown parameters and inputs, the model was embedded within a
      nonlinear estimation routine to minimize the deviations between model and data
      for CO2, O2, and N2 flows during expiration. Three groups, each of six
      individuals, were studied: young (20-30 yr); old (70-80 yr); and patients with
      mild to moderate chronic obstructive pulmonary disease (COPD). Each participant
      undertook a 15-min measurement protocol six times. For all parameters reflecting
      inhomogeneity, highly significant differences were found between the three
      participant groups ( P < 0.001, ANOVA). Intraclass correlation coefficients were
      0.96, 0.99, and 0.94 for the parameters reflecting inhomogeneity in deadspace,
      compliance, and vascular conductance, respectively. We conclude that, for the
      particular participants selected, highly repeatable estimates for parameters
      reflecting inhomogeneity could be obtained from noninvasive measurements of
      respiratory gas exchange. NEW & NOTEWORTHY This study describes a new method,
      based on highly precise measures of gas exchange, that quantifies three
      distributions that are intrinsic to the lung. These distributions represent three
      fundamentally different types of inhomogeneity that together give rise to
      ventilation-perfusion mismatch and result in impaired gas exchange. The
      measurement technique has potentially broad clinical applicability because it is
      simple for both patient and operator, it does not involve ionizing radiation, and
      it is completely noninvasive.

PMID- 29074715
TI  - Attittudes of staff members towards video recording in the delivery room.

PMID- 29074716
TI  - Antimicrobial resistance in UK neonatal units: neonIN infection surveillance
      network.
AB  - OBJECTIVE: To define the susceptibilities of the common causative pathogens of
      neonatal sepsis in the UK. DESIGN: Retrospective analysis of the prospectively
      collected neonIN infection surveillance network data between 2005 and 2014.
      SETTING: 30 neonatal units in the UK. PATIENTS: Newborns admitted to
      participating neonatal units who return a positive blood, cerebrospinal fluid or
      urine culture and are treated with at least 5 days of appropriate antibiotics.
      RESULTS: 1568 isolates with recorded antimicrobial data were collected including
      328 early-onset sepsis (EOS) isolates and 1240 late-onset sepsis (LOS) isolates.
      The majority of EOS pathogens (>92%) were susceptible to the four empirical
      commonly used antimicrobial combinations (eg, 93% for
      benzylpenicillin/gentamicin), while LOS pathogens demonstrated higher levels of
      resistance (eg, 89% for flucloxacillin/gentamicin). Among infants<1500 g and <32
      weeks gestation, an amoxicillin/gentamicin combination demonstrated a trend
      towards improved coverage of EOS isolates than benzylpenicillin/gentamicin (93%
      vs 86%, p=0.211). CONCLUSIONS: This analysis provides insights into the patterns
      of antimicrobial resistance among UK neonatal pathogens. These data will inform
      areas of future research and can be used to update national evidence-based
      guidelines on antimicrobial usage.

PMID- 29074718
TI  - Timing is everything.

PMID- 29074717
TI  - 2% chlorhexidine-70% isopropyl alcohol versus 10% povidone-iodine for insertion
      site cleaning before central line insertion in preterm infants: a randomised
      trial.
AB  - OBJECTIVE: To determine whether 2% chlorhexidine gluconate-70% isopropyl alcohol
      (CHX-IA) is superior to 10% aqueous povidone-iodine (PI) in preventing catheter
      related blood stream infection (CR-BSI) when used to clean insertion sites before
      placing central venous catheters (CVCs) in preterm infants. DESIGN: Randomised
      controlled trial. SETTING: Two neonatal intensive care units (NICUs). PATIENTS:
      Infants <31 weeks' gestation who had a CVC inserted. INTERVENTIONS: Insertion
      site was cleaned with CHX-IA or PI. Caregivers were not masked to group
      assignment. MAIN OUTCOME MEASURES: Primary outcome was CR-BSI determined by one
      microbiologist who was masked to group assignment. Secondary outcomes included
      skin reactions to study solution and thyroid dysfunction. RESULTS: We enrolled
      304 infants (CHX-IA 148 vs PI 156) in whom 815 CVCs (CHX-IA 384 vs PI 431) were
      inserted and remained in situ for 3078 (CHX-IA 1465 vs PI 1613) days. We found no
      differences between the groups in the proportion of infants with CR-BSI (CHX-IA
      7% vs PI 5%, p=0.631), the proportion of CVCs complicated by CR-BSI or the rate
      of CR-BSI per 1000 catheter days. Skin reaction rates were low (<1% CVC insertion
      episodes) and not different between the groups. More infants in the PI group had
      raised thyroid-stimulating hormone levels and were treated with thyroxine (CHX-IA
      0% vs PI 5%, p=0.003). CONCLUSIONS: We did not find a difference in the rate of
      CR-BSI between preterm infants treated with CHX-IA and PI, and more infants
      treated with PI had thyroid dysfunction. However, our study was not adequately
      powered to detect a difference in our primary outcome and a larger trial is
      required to confirm our findings. TRIAL REGISTRATION: This study was registered
      with the EU clinical trials register before the first patient was enrolled
      (Eudract 2011-002962-19). (https://www.clinicaltrialsregister.eu).

PMID- 29074719
TI  - Decision-making at the limits of viability: recognising the influence of parental
      factors.

PMID- 29074720
TI  - Variation in hospital mortality in an Australian neonatal intensive care unit
      network.
AB  - BACKGROUND: Studying centre-to-centre (CTC) variation in mortality rates is
      important because inferences about quality of care can be made permitting changes
      in practice to improve outcomes. However, comparisons between hospitals can be
      misleading unless there is adjustment for population characteristics and severity
      of illness. OBJECTIVE: We sought to report the risk-adjusted CTC variation in
      mortality among preterm infants born <32 weeks and admitted to all eight tertiary
      neonatal intensive care units (NICUs) in the New South Wales and the Australian
      Capital Territory Neonatal Network (NICUS), Australia. METHODS: We analysed
      routinely collected prospective data for births between 2007 and 2014. Adjusted
      mortality rates for each NICU were produced using a multiple logistic regression
      model. Output from this model was used to construct funnel plots. RESULTS: A
      total of 7212 live born infants <32 weeks gestation were admitted consecutively
      to network NICUs during the study period. NICUs differed in their patient
      populations and severity of illness.The overall unadjusted hospital mortality
      rate for the network was 7.9% (n=572 deaths). This varied from 5.3% in hospital E
      to 10.4% in hospital C. Adjusted mortality rates showed little CTC variation. No
      hospital reached the +99.8% control limit level on adjusted funnel plots.
      CONCLUSION: Characteristics of infants admitted to NICUs differ, and comparing
      unadjusted mortality rates should be avoided. Logistic regression-derived risk
      adjusted mortality rates plotted on funnel plots provide a powerful visual
      graphical tool for presenting quality performance data. CTC variation is readily
      identified, permitting hospitals to appraise their practices and start timely
      intervention.

PMID- 29074721
TI  - Imaging the neonatal brain in the 21st century: why, when and how?

PMID- 29074723
TI  - FDA Disperses $22 Million for Rare Diseases.
AB  - The FDA has awarded 15 grants totaling $22 million over 4 years through its
      Orphan Products Clinical Trials Grant Program. One third of the awards will
      support ongoing clinical trials of therapies for rare cancers for which there are
      few approved or effective treatment options.

PMID- 29074722
TI  - ECG monitoring in the delivery room is not reliable for all patients.

PMID- 29074724
TI  - Conversion of PRPS Hexamer to Monomer by AMPK-Mediated Phosphorylation Inhibits
      Nucleotide Synthesis in Response to Energy Stress.
AB  - Tumors override energy stress to grow. However, how nucleotide synthesis is
      regulated under energy stress is unclear. We demonstrate here that glucose
      deprivation or hypoxia results in the AMPK-mediated phosphorylation of
      phosphoribosyl pyrophosphate synthetase 1 (PRPS1) S180 and PRPS2 S183, leading to
      conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity,
      nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production.
      Knock-in of nonphosphorylatable PRPS1/2 mutants, which have uninhibited activity,
      in brain tumor cells under energy stress exhausts cellular ATP and NADPH and
      increases reactive oxygen species levels, thereby promoting cell apoptosis. The
      expression of those mutants inhibits brain tumor formation and enhances the
      inhibitory effect of the glycolysis inhibitor 2-deoxy-d-glucose on tumor growth.
      Our findings highlight the significance of recalibrating tumor cell metabolism by
      fine-tuning nucleotide and NAD synthesis in tumor growth.Significance: Our
      findings elucidate an instrumental function of AMPK in direct regulation of
      nucleic acid and NAD synthesis in tumor cells in response to energy stress. AMPK
      phosphorylates PRPS1/2, converts PRPS1/2 hexamers to monomers, and inhibits
      PRPS1/2 activity and subsequent nucleotide and NAD synthesis to maintain tumor
      cell growth and survival. Cancer Discov; 8(1); 94-107. (c)2017 AACR.This article
      is highlighted in the In This Issue feature, p. 1.

PMID- 29074726
TI  - Outcomes following polypectomy for malignant colorectal polyps are similar to
      those following surgery in the general population.
AB  - OBJECTIVE: Population-based studies on colorectal malignant polyps (MPs) are
      scarce. The aim of this study was to describe time trends in the incidence of
      colorectal MPs before and after the introduction of a colorectal mass-screening
      programmein 2003 and to assess outcomes (survival and recurrence) after
      endoscopic or surgical resection in patients with MPs. DESIGN: We included 411
      patients with MPs diagnosed between 1982 and 2011 in a well-defined population.
      Age-standardised incidence rates were calculated. Univariate and multivariate 5
      year recurrence and net survival analyses were performed according to gross
      morphology. RESULTS: Age-standardised incidence of MPs in patients aged 50-74
      years doubled from 5.4 in 1982-2002 to 10.9 per 100 000 in 2003-2011.
      Pedunculated MPs were more frequently resected endoscopically (38.2%) than were
      sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a
      pathological margin >=1 mm, the 5 -year cumulative recurrence rate did not differ
      significantly between surgical and endoscopic resection (8.2% and 2.4%,
      respectively). For patients with sessile MPs, it was 3.0% after first-line or
      second-line surgical resection, 8.6% after endoscopic resection and 17.9% after
      transanal resection (p=0.016). The recurrence rate decreased dramatically for
      patients with sessile MPs from 11.3% (1982-2002) to 1.2% (2003-2009) (p=0.010)
      and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five
      year net survival was 81.0% when pathological margins were <1 mm and 95.6% when
      >=1 mm (p=0.024). CONCLUSION: Outcomes following polypectomy in patients with a
      pathological margin >=1 mm are similar to those following surgery in the general
      population. Endoscopic resection needs to be completed by surgery if pathological
      margins are less than 1 mm.

PMID- 29074725
TI  - Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage
      accumulation in mice.
AB  - OBJECTIVE: Obesity is a risk factor for non-alcoholic steatohepatitis (NASH).
      This risk has been attributed to visceral adipose tissue (vAT) expansion
      associated with increased proinflammatory mediators. Accumulation of CD11c+
      proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT
      inflammation. We investigated the role of ATMs in hepatic inflammation during
      NASH development. DESIGN: vAT isolated from lean, obese or ATM-depleted (using
      clodronate liposomes) obese mice was transplanted to lean ldlr-/- acceptor mice.
      Systemic and hepatic inflammation was assessed either after 2 weeks on standard
      chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. RESULTS:
      Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage
      content compared with lean-transplanted mice, worsening liver damage. ATM
      depletion prior to vAT transplantation reduced this increased hepatic macrophage
      accumulation. On chow, vAT transplantation induced a more pronounced increase in
      circulating and hepatic neutrophil numbers in obese-transplanted than lean
      transplanted mice, while ATM depletion prior to vAT transplantation reversed this
      effect. Microarray analysis of fluorescence-activated cell sorting of CD11c+ and
      CD11c- macrophages isolated from donor adipose tissue showed that obesity
      resulted in enhanced expression of neutrophil chemotaxis genes specifically in
      CD11c+ ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and
      CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of
      obese individuals correlated with vAT expression of neutrophil chemotactic genes
      and with hepatic expression of neutrophil and macrophage marker genes.
      CONCLUSION: ATMs from obese vAT induce hepatic macrophage accumulation during
      NASH development, possibly by enhancing neutrophil recruitment.

PMID- 29074728
TI  - Compliance with nutrition screening in a children's hospital.
AB  - INTRODUCTION: There has been an increased emphasis on the nutritional care of
      children in hospital with the recognition that those admitted to hospital,
      particularly with chronic conditions, are at significant nutrition risk. However,
      although nutrition risk screening tools (NRST) are widely used in acute hospital
      settings compliance with their use is poorly reported. METHODS: One-day cross
      sectional audit of anthropometry/NRST records, Southampton Children's Hospital.
      Inclusion criteria were all in-patients present on the ward between 8 am and 4
      pm. Comparison was made with previous data. RESULTS: One hundred and thirteen
      records were reviewed. Anthropometric measures; weight recorded in 96.4%
      length/height recorded in 64% . This reflects a significant improvement on
      previous length/height data of 19%. Compliance with NRST was poor; only 17% of
      records were completed. CONCLUSION: Compliance with basic anthropometry was high
      and better than previously reported although use of nutritional screening tools
      was poor. This raises questions about the usefulness of current tools in clinical
      practice and whether measurement of height, weight and assessment of intake and
      nutrition risk may be more appropriate.

PMID- 29074729
TI  - Understanding and improving the experience of paediatricians in training.

PMID- 29074727
TI  - Liver Reptin/RUVBL2 controls glucose and lipid metabolism with opposite actions
      on mTORC1 and mTORC2 signalling.
AB  - OBJECTIVE: The AAA+ ATPase Reptin is overexpressed in hepatocellular carcinoma
      and preclinical studies indicate that it could be a relevant therapeutic target.
      However, its physiological and pathophysiological roles in vivo remain unknown.
      This study aimed to determine the role of Reptin in mammalian adult liver. DESIGN
      AND RESULTS: We generated an inducible liver-specific Reptin knockout (RepinLKO )
      mouse model. Following Reptin invalidation, mice displayed decreased body and fat
      mass, hypoglycaemia and hypolipidaemia. This was associated with decreased
      hepatic mTOR protein abundance. Further experiments in primary hepatocytes
      demonstrated that Reptin maintains mTOR protein level through its ATPase
      activity. Unexpectedly, loss or inhibition of Reptin induced an opposite effect
      on mTORC1 and mTORC2 signalling, with: (1) strong inhibition of hepatic mTORC1
      activity, likely responsible for the reduction of hepatocytes cell size, for
      decreased de novo lipogenesis and cholesterol transcriptional programmes and (2)
      enhancement of mTORC2 activity associated with inhibition of the gluconeogenesis
      transcriptional programme and hepatic glucose production. Consequently, the role
      of hepatic Reptin in the pathogenesis of insulin resistance (IR) and non
      alcoholic fatty liver disease consecutive to a high-fat diet was investigated. We
      found that Reptin deletion completely rescued pathological phenotypes associated
      with IR, including glucose intolerance, hyperglycaemia, hyperlipidaemia and
      hepatic steatosis. CONCLUSION: We show here that the AAA +ATPase Reptin is a
      regulator of mTOR signalling in the liver and global glucido-lipidic homeostasis.
      Inhibition of hepatic Reptin expression or activity represents a new therapeutic
      perspective for metabolic syndrome.

PMID- 29074730
TI  - Examining growth monitoring practices for children in primary care.

PMID- 29074731
TI  - Sleep disturbance in family caregivers of children who depend on medical
      technology.
AB  - OBJECTIVES: Family caregivers of children who depend on medical technology (CMT)
      provide highly skilled care up to 24 hours per day. Sleep disruption places
      family caregivers at risk for poor health and related outcomes that threaten
      their long-term caregiving capacity. Few studies exist that have measured sleep
      in family caregivers, and most have relied entirely on subjective measures.
      METHODS: In a prospective cohort study, family caregivers of CMT (n=42) and
      caregivers of healthy children (n=43) were recruited. Actigraphy data and a
      concurrent sleep diary were collected for 6 days/7 nights. Measures of sleep
      quality, depression, sleepiness, fatigue and quality of life were also
      administered. RESULTS: Family caregivers of CMT averaged fewer hours of sleep per
      night (mean (SD)) (6.56 +/- 1.4 vs 7.21 +/- 0.6, p=0.02) of poorer quality (7.75
      +/- 2.9 vs 5.45 +/- 2.8, p<0.01) than the control group. Three times as many
      family caregivers of CMT scored in the range for significant depressive
      symptomatology (12(33%) vs 4(10%), p=0.01) and experienced excessive daytime
      sleepiness (16(38%) vs 5(12%), p<0.01). Fatigue was also more problematic among
      family caregivers of CMT (22.12 +/- 9.1 vs 17.44 +/- 9.0, p=0.02). CONCLUSIONS:
      Family caregivers of CMT are at risk of acute and chronic sleep deprivation,
      psychological distress and impaired daytime function that may threaten their
      capacity for sustained caregiving. Family caregivers of CMT may be important
      targets for screening for sleep disorders and the development of novel sleep
      promoting interventions.

PMID- 29074732
TI  - Question 1: How safe are ACE inhibitors for heart failure in children?

PMID- 29074733
TI  - RCPCH invited reviews of services: how they can help.

PMID- 29074734
TI  - The impact of out-of-hospital models of care on paediatric emergency department
      presentations.
AB  - OBJECTIVE: To estimate the potential impact of enhanced primary care and new out
      of-hospital models (OOHMs) on emergency department (ED) presentations by children
      and young people (CYP). DESIGN: Observational study. PATIENTS & SETTING: Data
      collected prospectively on 3020 CYP 0-17.9 years from 6 London EDs during 14 days
      by 25 supernumerary clinicians. CYP with transient acute illness, exacerbation of
      long-term condition (LTC), complex LTC/disability and injury/trauma were
      considered manageable within OOHM. OOHMs assessed included nurse-led services,
      multispecialty community provider (MCP), primary and acute care system (PACS)
      plus current and enhanced primary care. MEASURES: Diagnosis, severity; record of
      investigations, management and outcome that occurred; objective assessment of
      clinical need and potential alternative management options/destinations. RESULTS:
      Of the patients 95.6% had diagnoses appropriate for OOHM. Most presentations
      required assessment by a clinician with skills in assessing illness (39.6%) or
      injuries (30.9%). One thousand two hundred and ninety-one (42.75%) required no
      investigations and 1007 (33.3%) were provided only with reassurance. Of the
      presentations 42.2% were judged to have been totally avoidable if the family had
      had better health education.Of the patients 26.1% were judged appropriate for
      current primary care (community pharmacy or general practice) with 31.5%
      appropriate for the combination of enhanced general practice and community
      pharmacy. Proportions suitable for new models were 14.1% for the nurse-led acute
      illness team, MCP 25.7%, GP federation CYP service 44.6%, comprehensive walk-in
      centre for CYP 64.3% and 75.5% for a PACS. CONCLUSIONS: High proportions of ED
      presentations by CYP could potentially be managed in new OOHMs or by enhancement
      of existing primary care.

PMID- 29074735
TI  - "Culture of short termism" threatens health and care services, warn lords.

PMID- 29074737
TI  - LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti
      Brush Border Antibody Disease.
AB  - Primary renal tubulointerstitial disease resulting from proximal tubule antigen
      specific antibodies and immune complex formation has not been well characterized
      in humans. We report a cohort of patients with a distinct, underappreciated
      kidney disease characterized by kidney antibrush border antibodies and renal
      failure (ABBA disease). We identified ten patients with ABBA disease who had a
      combination of proximal tubule damage, IgG-positive immune deposits in the
      tubular basement membrane, and circulating antibodies reactive with normal human
      kidney proximal tubular brush border. All but one of the patients also had
      segmental glomerular deposits on renal biopsy specimen. Patients with ABBA
      disease were elderly and presented with AKI and subnephrotic proteinuria. Serum
      from all patients but not controls recognized a high molecular weight protein in
      renal tubular protein extracts that we identified as LDL receptor-related protein
      2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry.
      Immunostaining revealed that LRP2 specifically colocalized with IgG in the
      tubular immune deposits on the ABBA biopsy specimen but not the control specimen
      analyzed. Finally, ABBA serum samples but not control samples showed reactivity
      against recombinantly expressed N-terminal LRP2 fragments on Western blots and
      immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This
      case series details the clinicopathologic findings of patients with ABBA disease
      and shows that the antigenic target of these autoantibodies is LRP2. Future
      studies are needed to determine the disease prevalence, stimulus for ABBA, and
      optimal treatment.

PMID- 29074738
TI  - Surprising Enhancement of Fibrosis by Tubule-Specific Deletion of the TGF-beta
      Receptor: A New Twist on an Old Paradigm.

PMID- 29074736
TI  - Molecular basis of CENP-C association with the CENP-A nucleosome at yeast
      centromeres.
AB  - Histone CENP-A-containing nucleosomes play an important role in nucleating
      kinetochores at centromeres for chromosome segregation. However, the molecular
      mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not
      well understood. Here, we report the finding of a new function for the budding
      yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein
      Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an
      important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome
      dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA. Both
      interactions are directed by a contiguous DNA- and histone-binding domain (DHBD)
      harboring the conserved CENP-C motif, an AT hook, and RK clusters (clusters
      enriched for arginine-lysine residues). Human CENP-C has two related DHBDs that
      bind preferentially to DNA sequences of higher AT content. Our findings suggest
      that a DNA composition-based mechanism together with residues characteristic for
      the CENP-A histone variant contribute to the specification of centromere
      identity.

PMID- 29074740
TI  - Comment on "The extent of forest in dryland biomes".
AB  - Bastin et al (Reports, 12 May 2017, p. 635) claim to have discovered 467 million
      hectares of new dryland forest. We would argue that these additional areas are
      not completely "new" and that some have been reported before. A second
      shortcoming is that not all sources of uncertainty are considered; the
      uncertainty could be much higher than the reported value of 3.5%.

PMID- 29074741
TI  - Response to Comment on "The extent of forest in dryland biomes".
AB  - Schepaschenko et al question our findings, claiming that we did not refer to all
      existing maps and that we did not account for all sources of uncertainty. In our
      response, we detail our selection criteria for reference maps, which clarify why
      the work of Schepaschenko et al was not used, and we explain why our uncertainty
      assessment is complete and how it was misunderstood by Schepaschenko et al.

PMID- 29074739
TI  - Genome-wide discovery of active regulatory elements and transcription factor
      footprints in Caenorhabditis elegans using DNase-seq.
AB  - Deep sequencing of size-selected DNase I-treated chromatin (DNase-seq) allows
      high-resolution measurement of chromatin accessibility to DNase I cleavage,
      permitting identification of de novo active cis-regulatory modules (CRMs) and
      individual transcription factor (TF) binding sites. We adapted DNase-seq to
      nuclei isolated from C. elegans embryos and L1 arrest larvae to generate high
      resolution maps of TF binding. Over half of embryonic DNase I hypersensitive
      sites (DHSs) were annotated as noncoding, with 24% in intergenic, 12% in
      promoters, and 28% in introns, with similar statistics observed in L1 arrest
      larvae. Noncoding DHSs are highly conserved and enriched in marks of enhancer
      activity and transcription. We validated noncoding DHSs against known enhancers
      from myo-2, myo-3, hlh-1, elt-2, and lin-26/lir-1 and recapitulated 15 of 17
      known enhancers. We then mined DNase-seq data to identify putative active CRMs
      and TF footprints. Using DNase-seq data improved predictions of tissue-specific
      expression compared with motifs alone. In a pilot functional test, 10 of 15 DHSs
      from pha-4, icl-1, and ceh-13 drove reporter gene expression in transgenic C.
      elegans Overall, we provide experimental annotation of 26,644 putative CRMs in
      the embryo containing 55,890 TF footprints, as well as 15,841 putative CRMs in
      the L1 arrest larvae containing 32,685 TF footprints.

PMID- 29074742
TI  - Nip misinformation in the bud.

PMID- 29074744
TI  - Echoes of Ebola as plague hits Madagascar.

PMID- 29074745
TI  - Neandertals gave 'lost' African DNA back to moderns.

PMID- 29074747
TI  - NASA weighs trimming WFIRST to hold down costs.

PMID- 29074746
TI  - 'Base editors' open new way to fix mutations.

PMID- 29074748
TI  - Revamp animal research rules, report urges.

PMID- 29074749
TI  - The electron is still round-for now.

PMID- 29074750
TI  - Medicine's future?

PMID- 29074751
TI  - Roads to riches or ruin?

PMID- 29074752
TI  - Plasmepsins on the antimalarial hit list.

PMID- 29074753
TI  - The bacterium has landed.

PMID- 29074754
TI  - The art of empty space.

PMID- 29074755
TI  - Designing tougher elastomers with ionomers.

PMID- 29074756
TI  - A peptide mimic of an antibody.

PMID- 29074757
TI  - Ethics of maternal vaccination.

PMID- 29074758
TI  - Assembling the brain from deep within.

PMID- 29074759
TI  - Overriding sleep.

PMID- 29074760
TI  - Sleep on it.

PMID- 29074761
TI  - Editorial retraction.

PMID- 29074762
TI  - France's risky vaccine mandates.

PMID- 29074763
TI  - Missed opportunities in Yachay.

PMID- 29074764
TI  - Neuroscience: In search of new concepts.

PMID- 29074765
TI  - The emperor's new wardrobe: Rebalancing diversity of animal models in
      neuroscience research.
AB  - The neuroscience field is steaming ahead, fueled by a revolution in cutting-edge
      technologies. Concurrently, another revolution has been underway-the diversity of
      species utilized for neuroscience research is sharply declining, as the field
      converges on a few selected model organisms. Here, from the perspective of a
      young scientist, I naively ask: Is the great diversity of questions in
      neuroscience best studied in only a handful of animal models? I review some of
      the limitations the field is facing following this convergence and how these can
      be rectified by increasing the diversity of appropriate model species. I propose
      that at this exciting time of revolution in genetics and device technologies,
      neuroscience might be ready to diversify again, if provided the appropriate
      support.

PMID- 29074766
TI  - Big data and the industrialization of neuroscience: A safe roadmap for
      understanding the brain?
AB  - New technologies in neuroscience generate reams of data at an exponentially
      increasing rate, spurring the design of very-large-scale data-mining initiatives.
      Several supranational ventures are contemplating the possibility of achieving,
      within the next decade(s), full simulation of the human brain.

PMID- 29074767
TI  - What constitutes the prefrontal cortex?
AB  - During evolution, the prefrontal region grew in size relative to the rest of the
      cortex. It reached its largest extent in the human brain, where it constitutes
      30% of the total cortical area. This growth was accompanied by phylogenetic
      differentiation of the cortical areas. It has been argued that the human brain
      holds prefrontal regions that are both qualitatively and functionally unique.
      Present-day neuroscientists studying the prefrontal cortex increasingly use mice.
      An important goal is to reveal how the prefrontal cortex enables complex
      behavior. However, the prefrontal cortex still lacks a conclusive definition. The
      structure and function of this brain area across species remain unresolved. This
      state of affairs is often overlooked, warranting renewed focus on what the
      prefrontal cortex is and does.

PMID- 29074768
TI  - Space and time in the brain.
AB  - Nothing is more intuitive, yet more complex, than the concepts of space and time.
      In contrast to spacetime in physics, space and time in neuroscience remain
      separate coordinates to which we attach our observations. Investigators of
      navigation and memory relate neuronal activity to position, distance, time point,
      and duration and compare these parameters to units of measuring instruments.
      Although spatial-temporal sequences of brain activity often correlate with
      distance and duration measures, these correlations may not correspond to neuronal
      representations of space or time. Neither instruments nor brains sense space or
      time. Neuronal activity can be described as a succession of events without
      resorting to the concepts of space or time. Instead of searching for brain
      representations of our preconceived ideas, we suggest investigating how brain
      mechanisms give rise to inferential, model-building explanations.

PMID- 29074769
TI  - What is consciousness, and could machines have it?
AB  - The controversial question of whether machines may ever be conscious must be
      based on a careful consideration of how consciousness arises in the only physical
      system that undoubtedly possesses it: the human brain. We suggest that the word
      "consciousness" conflates two different types of information-processing
      computations in the brain: the selection of information for global broadcasting,
      thus making it flexibly available for computation and report (C1, consciousness
      in the first sense), and the self-monitoring of those computations, leading to a
      subjective sense of certainty or error (C2, consciousness in the second sense).
      We argue that despite their recent successes, current machines are still mostly
      implementing computations that reflect unconscious processing (C0) in the human
      brain. We review the psychological and neural science of unconscious (C0) and
      conscious computations (C1 and C2) and outline how they may inspire novel machine
      architectures.

PMID- 29074770
TI  - Toughening elastomers using mussel-inspired iron-catechol complexes.
AB  - Materials often exhibit a trade-off between stiffness and extensibility; for
      example, strengthening elastomers by increasing their cross-link density leads to
      embrittlement and decreased toughness. Inspired by cuticles of marine mussel
      byssi, we circumvent this inherent trade-off by incorporating sacrificial,
      reversible iron-catechol cross-links into a dry, loosely cross-linked epoxy
      network. The iron-containing network exhibits two to three orders of magnitude
      increases in stiffness, tensile strength, and tensile toughness compared to its
      iron-free precursor while gaining recoverable hysteretic energy dissipation and
      maintaining its original extensibility. Compared to previous realizations of this
      chemistry in hydrogels, the dry nature of the network enables larger property
      enhancement owing to the cooperative effects of both the increased cross-link
      density given by the reversible iron-catecholate complexes and the chain
      restricting ionomeric nanodomains that they form.

PMID- 29074771
TI  - Atomic structure of sensitive battery materials and interfaces revealed by cryo
      electron microscopy.
AB  - Whereas standard transmission electron microscopy studies are unable to preserve
      the native state of chemically reactive and beam-sensitive battery materials
      after operation, such materials remain pristine at cryogenic conditions. It is
      then possible to atomically resolve individual lithium metal atoms and their
      interface with the solid electrolyte interphase (SEI). We observe that dendrites
      in carbonate-based electrolytes grow along the <111> (preferred), <110>, or <211>
      directions as faceted, single-crystalline nanowires. These growth directions can
      change at kinks with no observable crystallographic defect. Furthermore, we
      reveal distinct SEI nanostructures formed in different electrolytes.

PMID- 29074772
TI  - Size effect in ion transport through angstrom-scale slits.
AB  - In the field of nanofluidics, it has been an ultimate but seemingly distant goal
      to controllably fabricate capillaries with dimensions approaching the size of
      small ions and water molecules. We report ion transport through ultimately narrow
      slits that are fabricated by effectively removing a single atomic plane from a
      bulk crystal. The atomically flat angstrom-scale slits exhibit little surface
      charge, allowing elucidation of the role of steric effects. We find that ions
      with hydrated diameters larger than the slit size can still permeate through,
      albeit with reduced mobility. The confinement also leads to a notable asymmetry
      between anions and cations of the same diameter. Our results provide a platform
      for studying the effects of angstrom-scale confinement, which is important for
      the development of nanofluidics, molecular separation, and other nanoscale
      technologies.

PMID- 29074773
TI  - Tunable porous nanoallotropes prepared by post-assembly etching of binary
      nanoparticle superlattices.
AB  - Self-assembly of inorganic nanoparticles has been used to prepare hundreds of
      different colloidal crystals, but almost invariably with the restriction that the
      particles must be densely packed. Here, we show that non-close-packed
      nanoparticle arrays can be fabricated through the selective removal of one of two
      components comprising binary nanoparticle superlattices. First, a variety of
      binary nanoparticle superlattices were prepared at the liquid-air interface,
      including several arrangements that were previously unknown. Molecular dynamics
      simulations revealed the particular role of the liquid in templating the
      formation of superlattices not achievable through self-assembly in bulk solution.
      Second, upon stabilization, all of these binary superlattices could be
      transformed into distinct "nanoallotropes"-nanoporous materials having the same
      chemical composition but differing in their nanoscale architectures.

PMID- 29074774
TI  - Plasmepsins IX and X are essential and druggable mediators of malaria parasite
      egress and invasion.
AB  - Proteases of the malaria parasite Plasmodium falciparum have long been
      investigated as drug targets. The P. falciparum genome encodes 10 aspartic
      proteases called plasmepsins, which are involved in diverse cellular processes.
      Most have been studied extensively but the functions of plasmepsins IX and X
      (PMIX and PMX) were unknown. Here we show that PMIX is essential for erythrocyte
      invasion, acting on rhoptry secretory organelle biogenesis. In contrast, PMX is
      essential for both egress and invasion, controlling maturation of the subtilisin
      like serine protease SUB1 in exoneme secretory vesicles. We have identified
      compounds with potent antimalarial activity targeting PMX, including a compound
      known to have oral efficacy in a mouse model of malaria.

PMID- 29074776
TI  - Nepsilon-Fatty acylation of Rho GTPases by a MARTX toxin effector.
AB  - The multifunctional autoprocessing repeats-in-toxin (MARTX) toxins are a family
      of large toxins that are extensively distributed in bacterial pathogens. MARTX
      toxins are autocatalytically cleaved to multiple effector domains, which are
      released into host cells to modulate the host signaling pathways. The Rho
      guanosine triphosphatase (GTPase) inactivation domain (RID), a conserved effector
      domain of MARTX toxins, is implicated in cell rounding by disrupting the host
      actin cytoskeleton. We found that the RID is an Nepsilon-fatty acyltransferase
      that covalently modifies the lysine residues in the C-terminal polybasic region
      of Rho GTPases. The resulting fatty acylation inhibited Rho GTPases and disrupted
      Rho GTPase-mediated signaling in the host. Thus, RID can mediate the lysine
      Nepsilon-fatty acylation of mammalian proteins and represents a family of toxins
      that harbor N-fatty acyltransferase activities in bacterial pathogens.

PMID- 29074775
TI  - A multistage antimalarial targets the plasmepsins IX and X essential for invasion
      and egress.
AB  - Regulated exocytosis by secretory organelles is important for malaria parasite
      invasion and egress. Many parasite effector proteins, including perforins,
      adhesins, and proteases, are extensively proteolytically processed both pre- and
      postexocytosis. Here we report the multistage antiplasmodial activity of the
      aspartic protease inhibitor hydroxyl-ethyl-amine-based scaffold compound 49c.
      This scaffold inhibits the preexocytosis processing of several secreted rhoptry
      and microneme proteins by targeting the corresponding maturases plasmepsins IX
      (PMIX) and X (PMX), respectively. Conditional excision of PMIX revealed its
      crucial role in invasion, and recombinantly active PMIX and PMX cleave egress and
      invasion factors in a 49c-sensitive manner.

PMID- 29074777
TI  - Second messenger-mediated tactile response by a bacterial rotary motor.
AB  - When bacteria encounter surfaces, they respond with surface colonization and
      virulence induction. The mechanisms of bacterial mechanosensation and downstream
      signaling remain poorly understood. Here, we describe a tactile sensing cascade
      in Caulobacter crescentus in which the flagellar motor acts as sensor. Surface
      induced motor interference stimulated the production of the second messenger
      cyclic diguanylate by the motor-associated diguanylate cyclase DgcB. This led to
      the allosteric activation of the glycosyltransferase HfsJ to promote rapid
      synthesis of a polysaccharide adhesin and surface anchoring. Although the
      membrane-embedded motor unit was essential for surface sensing, mutants that lack
      external flagellar structures were hypersensitive to mechanical stimuli. Thus,
      the bacterial flagellar motor acts as a tetherless sensor reminiscent of
      mechanosensitive channels.

PMID- 29074779
TI  - Lessons from learning disabilities.

PMID- 29074782
TI  - Vets can be specialists in general practice.

PMID- 29074780
TI  - New measures to tackle the 'wild west' world of online puppy sales.

PMID- 29074778
TI  - Obstruction of pilus retraction stimulates bacterial surface sensing.
AB  - It is critical for bacteria to recognize surface contact and initiate
      physiological changes required for surface-associated lifestyles. Ubiquitous
      microbial appendages called pili are involved in sensing surfaces and
      facilitating downstream behaviors, but the mechanism by which pili mediate
      surface sensing has been unclear. We visualized Caulobacter crescentus pili
      undergoing dynamic cycles of extension and retraction. Within seconds of surface
      contact, these cycles ceased, which coincided with synthesis of the adhesive
      holdfast required for attachment. Physically blocking pili imposed resistance to
      pilus retraction, which was sufficient to stimulate holdfast synthesis without
      surface contact. Thus, to sense surfaces, bacteria use the resistance on
      retracting, surface-bound pili that occurs upon surface contact.

PMID- 29074783
TI  - Farming propped up by antimicrobials 'will have to go' says chief vet.

PMID- 29074784
TI  - Bluetongue confirmed in UK cattle.

PMID- 29074789
TI  - Novel gene therapy gives competition horses new lease of life after lameness.

PMID- 29074790
TI  - Vets urged to support vital bird of prey conservation.

PMID- 29074791
TI  - Medicines update.

PMID- 29074793
TI  - Equine infectious anaemia in Europe: an ongoing threat to the UK.
AB  - Helen Roberts of Defra's International Disease Monitoring team sets out the
      situation regarding equine infectious anaemia in Europe, the threat to the UK and
      the expectations of disease control measures in light of an outbreak being
      detected.

PMID- 29074795
TI  - Correction.

PMID- 29074794
TI  - Keeping reptiles and amphibians as pets: challenges and rewards.

PMID- 29074796
TI  - Future of keeping pet reptiles and amphibians: animal welfare and public health
      perspective.
AB  - In a review summary on page 450, Pasmans and others discuss the future of keeping
      reptiles and amphibians as pets. Here, Clifford Warwick and others discuss the
      animal welfare and public health implications of exotic pet business.

PMID- 29074797
TI  - Veterinary homeopathy: a defence.

PMID- 29074798
TI  - Benchmarking antimicrobial use.

PMID- 29074799
TI  - The authors of 'Comparison of veterinary drugs and veterinary homeopathy: part 1
      and 2', respond.

PMID- 29074800
TI  - Increasing diversity in the 'My view' column.

PMID- 29074801
TI  - ?

PMID- 29074802
TI  - Extreme breedingin horses.

PMID- 29074809
TI  - If you can handle vet school, you can handle anything.
AB  - Jolle Kirpensteijn grew up in The Netherlands and now lives in the USA. He is the
      most recent recipient of the WSAVA's President's Award.

PMID- 29074812
TI  - Pleural effusion as a late complication of intravesical BCG treatment.

PMID- 29074811
TI  - Associations between emphysema-like lung on CT and incident airflow limitation: a
      general population-based cohort study.
AB  - Emphysema on CT is associated with accelerated lung function decline in heavy
      smokers and patients with COPD; however, in the general population, it is not
      known whether greater emphysema-like lung on CT is associated with incident COPD.
      We used data from 2045 adult participants without initial prebronchodilator
      airflow limitation, classified by FEV1/FVC<0.70, in the Multi-Ethnic Study of
      Atherosclerosis. Emphysema-like lung on baseline cardiac CT, defined as per cent
      low attenuation areas<-950HU>upper limit of normal, was associated with increased
      odds of incident airflow limitation at 5-year follow-up on both prebronchodilator
      (adjusted OR 2.62, 95% CI 1.47 to 4.67) and postbronchodilator (adjusted OR 4.38,
      95% CI 1.63 to 11.74) spirometry, independent of smoking history. These results
      support investigation into whether emphysema-like lung could be informative for
      COPD risk stratification.

PMID- 29074813
TI  - NERO: a pilot study but important step towards comprehensive management of
      obesity hypoventilation syndrome.

PMID- 29074814
TI  - Exacerbation risk and characterisation of the UK's asthma population from infants
      to old age.
AB  - BACKGROUND: Few studies have examined the characteristics of a general asthma
      population; most have focused on more severe patients or severe exacerbations.
      METHODS: This population-based cohort study, from April 2007 to September 2015,
      used linked primary and secondary care electronic healthcare records (Clinical
      Practice Research Datalink, Hospital Episode Statistics). Characteristics of four
      age cohorts, 'Under 5s', '5 to 17s', '18 to 54s', '55+', were described.
      Exacerbation risk factors, including asthma severity (measured by the British
      Thoracic Society (BTS) stepwise approach), were assessed using Poisson
      regression. RESULTS: 424 326 patients with current asthma were eligible (n,
      median follow-up: 'Under 5s'=17 320, 1 year; '5 to 17s'=82 707, 3.3 years; '18 to
      54s'=210 724, 4 years; '55+'=113 575, 5.1 years). Over 60% of the total study
      population had mild asthma (BTS steps 1/2). There were differences between the
      cohort's characteristics, including by gender, disease severity and exacerbation
      pattern. The rate of exacerbations was highest in the oldest cohort and lowest in
      the '5 to 17s' cohort (rate per 10 person-years (95% CI), 'Under 5s'=4.27 (4.18
      to 4.38), '5 to 17s'=1.48 (1.47 to 1.50), '18 to 54s'=3.22 (3.21 to 3.24),
      '55+'=9.40 (9.37 to 9.42)). In all cohorts, exacerbation rates increased with
      increasing asthma severity, after adjusting for confounders including gender,
      socioeconomic status, smoking, body mass index, atopy, rhinitis, gastro
      oesophageal reflux, anxiety, depression and COPD. CONCLUSION: The majority of UK
      patients with asthma had mild asthma and did not experience an exacerbation
      during follow-up. Patients aged >=55 years had the lowest proportion with mild
      asthma and highest rate of exacerbations; the opposite was found in patients aged
      between 5 and 18 years.

PMID- 29074815
TI  - Hyperbaric Oxygen Therapy in the Treatment of Ischemic Lower- Extremity Ulcers in
      Patients With Diabetes: Results of the DAMO2CLES Multicenter Randomized Clinical
      Trial.
AB  - OBJECTIVE: Conflicting evidence exists on the effects of hyperbaric oxygen
      therapy (HBOT) in the treatment of chronic ischemic leg ulcers. The aim of this
      trial was to investigate whether additional HBOT would benefit patients with
      diabetes and ischemic leg ulcers. RESEARCH DESIGN AND METHODS: Patients with
      diabetes with an ischemic wound (n = 120) were randomized to standard care (SC)
      without or with HBOT (SC+HBOT). Primary outcomes were limb salvage and wound
      healing after 12 months, as well as time to wound healing. Other end points were
      amputation-free survival (AFS) and mortality. RESULTS: Both groups contained 60
      patients. Limb salvage was achieved in 47 patients in the SC group vs. 53
      patients in the SC+HBOT group (risk difference [RD] 10% [95% CI -4 to 23]). After
      12 months, 28 index wounds were healed in the SC group vs. 30 in the SC+HBOT
      group (RD 3% [95% CI -14 to 21]). AFS was achieved in 41 patients in the SC group
      and 49 patients in the SC+HBOT group (RD 13% [95% CI -2 to 28]). In the SC+HBOT
      group, 21 patients (35%) were unable to complete the HBOT protocol as planned.
      Those who did had significantly fewer major amputations and higher AFS (RD for
      AFS 26% [95% CI 10-38]). CONCLUSIONS: Additional HBOT did not significantly
      improve complete wound healing or limb salvage in patients with diabetes and
      lower-limb ischemia.

PMID- 29074817
TI  - Association of Kidney Transplantation with Survival in Patients with Long
      Dialysis Exposure.
AB  - BACKGROUND AND OBJECTIVES: Evidence that kidney transplantation is associated
      with better survival compared to dialysis stems from data in populations with
      short durations of dialysis exposure. Recent changes in allocation policy
      increase access to transplantation for patients with longer dialysis exposure.
      The objective of this study was to determine the association of transplantation
      with survival in patients with >=10 years of dialysis treatment. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Our study of n=5365 patients in the Scientific
      Registry of Transplant Recipients determined the adjusted relative risk of death
      in recipients of a deceased donor kidney transplant after >=10 years of dialysis
      treatment compared with waitlisted patients with the same dialysis exposure in a
      time-dependent nonproportional hazards analysis. RESULTS: The adjusted relative
      risk of death in n=2320 transplant recipients compared with patients on dialysis
      who had equal lengths of follow-up from their 10-year dialysis anniversary was
      0.60 (95% confidence interval, 0.53 to 0.68), and this benefit was observed in a
      variety of patient subgroups, including patients >=65 years of age and patients
      with diabetes. However, transplant recipients were at higher risk of death for
      180 days after transplantation and did not derive survival benefit until 657 days
      after transplantation, despite receiving good-quality kidneys. The study patients
      were younger and had higher expected post-transplant survival than patients
      currently waitlisted with >=10 years of dialysis. CONCLUSIONS: Transplantation is
      associated with better survival in patients who were actively waitlisted with
      dialysis exposure >=10 years. Whether transplantation is associated with better
      survival in currently waitlisted patients with similar dialysis exposure and
      whether transplantation of lower-quality deceased donor kidneys is associated
      with better survival are uncertain.

PMID- 29074816
TI  - Prediction of Type 2 Diabetes by Hemoglobin A1c in Two Community-Based Cohorts.
AB  - OBJECTIVE: Hemoglobin A1c (HbA1c) can be used to assess type 2 diabetes (T2D)
      risk. We asked whether HbA1c was associated with T2D risk in four scenarios of
      clinical information availability: 1) HbA1c alone, 2) fasting laboratory tests,
      3) clinic data, and 4) fasting laboratory tests and clinic data. RESEARCH DESIGN
      AND METHODS: We studied a prospective cohort of white (N = 11,244) and black (N =
      2,294) middle-aged participants without diabetes in the Framingham Heart Study
      and Atherosclerosis Risk in Communities study. Association of HbA1c with incident
      T2D (defined by medication use or fasting glucose [FG] >=126 mg/dL) was evaluated
      in regression models adjusted for 1) age and sex (demographics); 2) demographics,
      FG, HDL, and triglycerides; 3) demographics, BMI, blood pressure, and T2D family
      history; or 4) all preceding covariates. We combined results from cohort and race
      analyses by random-effects meta-analyses. Subsidiary analyses tested the
      association of HbA1c with developing T2D within 8 years or only after 8 years.
      RESULTS: Over 20 years, 3,315 individuals developed T2D. With adjustment for
      demographics, the odds of T2D increased fourfold for each percentage-unit
      increase in HbA1c. The odds ratio (OR) was 4.00 (95% CI 3.14, 5.10) for blacks
      and 4.73 (3.10, 7.21) for whites, resulting in a combined OR of 4.50 (3.35,
      6.03). After adjustment for fasting laboratory tests and clinic data, the
      combined OR was 2.68 (2.15, 3.34) over 20 years, 5.79 (2.51, 13.36) within 8
      years, and 2.23 (1.94, 2.57) after 8 years. CONCLUSIONS: HbA1c predicts T2D in
      different common scenarios and is useful for identifying individuals with
      elevated T2D risk in both the short- and long-term.

PMID- 29074819
TI  - Continued Search for Therapies to Favorably Modify Phosphate and FGF23 Levels in
      CKD.

PMID- 29074820
TI  - Can aging be beneficial?

PMID- 29074818
TI  - Randomized Clinical Trial of Sevelamer Carbonate on Serum Klotho and Fibroblast
      Growth Factor 23 in CKD.
AB  - BACKGROUND AND OBJECTIVES: Epidemiologic studies suggest that higher serum
      phosphaturic hormone fibroblast growth factor 23 levels are associated with
      increase morbidity and mortality. The aim of the FGF23 Reduction Efficacy of a
      New Phosphate Binder in CKD Trial was to evaluate the effect of sevelamer
      carbonate on serum C-terminal fibroblast growth factor 23 levels in
      normophosphatemic patients with CKD stage 3b/4. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Patients with CKD, eGFR between 45 and 15 ml/min per 1.73 m2,
      fasting serum phosphate concentration >3.1 mg/dl, and serum C-terminal fibroblast
      growth factor 23 >80 relative units/ml were included in our double-blind, placebo
      controlled, randomized multicenter study. All patients received 100,000 IU
      cholecalciferol at time of randomization. Participants received either placebo or
      sevelamer carbonate 4.8 g daily during a 12-week period. Biologic parameters,
      including serum C-terminal fibroblast growth factor 23, intact fibroblast growth
      factor 23, and alpha-klotho, were evaluated at baseline and 12 weeks after
      inclusion. RESULTS: Of 96 screened patients, 78 (mean+/-SD age: 63+/-13 years
      old; 70% men; mean eGFR: 27+/-9 ml/min per 1.73 m2) met the inclusion criteria.
      At baseline, mean eGFR was 27+/-9 ml/min per 1.73 m2, mean serum phosphate level
      was 3.8+/-0.5 mg/dl, and median (interquartile range) serum C-terminal fibroblast
      growth factor 23 level was 157 (120-241) relative units/ml. After 12 weeks of
      treatment, urinary phosphate-to-creatinine ratio fell significantly in the
      sevelamer group. The sevelamer and placebo groups did not differ significantly in
      terms of median change in serum C-terminal fibroblast growth factor 23 levels:
      the median (interquartile range) change was 38 (-13-114) relative units/ml in the
      placebo group and 37 (-1-101) relative units/ml in the sevelamer group (P=0.77).
      There was no significant difference in serum intact fibroblast growth factor 23,
      alpha-klotho, or phosphate levels changes between the two groups. Serum total and
      LDL cholesterol levels fell significantly in the sevelamer group. CONCLUSIONS: In
      our double-blind, placebo-controlled, randomized study performed in
      normophosphatemic patients with CKD, a 12-week course of sevelamer carbonate
      significantly reduced phosphaturia without changing serum phosphorus but did not
      significantly modify serum C-terminal fibroblast growth factor 23 and intact
      fibroblast growth factor 23 or alpha-klotho levels.

PMID- 29074821
TI  - (Anti-)parallel evolution of lifespan.

PMID- 29074823
TI  - [Update on recent progress in vitamin D research. Vitamin D Metabolism and Its
      Regulation.]
AB  - Vitamin D is taken up from food as D2 and D3. Vitamin D3 is also synthesized from
      7-dehydrocholesterol in the skin by the exposure of ultraviolet B. The D2 and D3,
      which are called native vitamin D, are hydroxylated at C25 in the liver by CYP2R1
      and then at C1 in the kidney by CYP27B1, to be converted to an active vitamin D
      metabolite, 1,25-dihydroxyvitamin D[1,25(OH)2D]. CYP24A1 converts 25
      hydroxyvitamin D(25OHD)and 1,25(OH)2D to 24,25-dihydroxyvitamin D[24,25(OH)2D]and
      1,24,25-trihydroxyvitamin D[1,24,25(OH)3D], respectively, to decrease the level
      of 1,25(OH)2D. CYP27B1 and CYP24A1 are mainly expressed in the kidney but also
      detected in other tissues, and it is suggested that 1,25(OH)2D produced in the
      extra-renal tissues may exert its effects locally.

PMID- 29074822
TI  - Degeneration of the osteocyte network in the C57BL/6 mouse model of aging.
AB  - Age-related bone loss and associated fracture risk are major problems in
      musculoskeletal health. Osteocytes have emerged as key regulators of bone mass
      and as a therapeutic target for preventing bone loss. As aging is associated with
      changes in the osteocyte lacunocanalicular system, we focused on the responsible
      cellular mechanisms in osteocytes. Bone phenotypic analysis was performed in
      young-(5mo) and aged-(22mo) C57BL/6 mice and changes in bone structure/geometry
      correlated with alterations in osteocyte parameters determined using novel
      multiplexed-3D-confocal imaging techniques. Age-related bone changes analogous to
      those in humans were observed, including increased cortical diameter, decreased
      cortical thickness, reduced trabecular BV/TV and cortical porosities. This was
      associated with a dramatic reduction in osteocyte dendrite number and cell
      density, particularly in females, where osteocyte dendricity decreased linearly
      from 5, 12, 18 to 22mo and correlated significantly with cortical bone
      parameters. Reduced dendricity preceded decreased osteocyte number, suggesting
      dendrite loss may trigger loss of viability. Age-related degeneration of
      osteocyte networks may impair bone anabolic responses to loading and gender
      differences in osteocyte cell body and lacunar fluid volumes we observed in aged
      mice may lead to gender-related differences in mechanosensitivity. Therapies to
      preserve osteocyte dendricity and viability may be beneficial for bone health in
      aging.

PMID- 29074824
TI  - [Update on recent progress in vitamin D research. Vitamin D and bone, mineral
      metabolism.]
AB  - Vitamin D endocrine system is required for bone and mineral homeostasis through
      the active form of vitamin D[1alpha,25(OH)2D3]transported to the target organs,
      where the vitamin D receptor(VDR)is present. The biological significance of
      1alpha,25(OH)2D3-VDR signalling is regarded not only in classical target of
      vitamin D involved in calcium and phosphate homeostasis, such as intestine, bone,
      kidney and parathyroid glands, but also in many other non-classical target cells
      of vitamin D including skin keratinocytes, pancreatic beta cells, cardiomyocytes,
      T-lymphocytes, bone marrow macrophages, among others. Although 1alpha,25(OH)2D3
      VDR signalling in classical target organs of vitamin D has been extensively
      studied, its precise function in these target organs still needs further
      investigation.

PMID- 29074825
TI  - [Update on recent progress in vitamin D research. Vitamin D receptor and the
      nuclear receptor superfamily.]
AB  - The vitamin D receptor(VDR)is a ligand-dependent transcription factor of the
      nuclear receptor superfamily. VDR belongs to the NR1I subfamily along with other
      nuclear receptors involved in xenobiotic metabolism, such as pregnane X receptor.
      The oxysterol receptors liver X receptors alpha/beta and the bile acid receptor
      farnesoid X receptor belong to the NR1H subfamily, which are closely related to
      the NR1I subfamily. NR1I and NR1H nuclear receptors form heterodimers with
      retinoid X receptor. The active form of vitamin D, 1alpha,25-dihydroxyvitamin
      D3[1,25(OH)2D3], acts as a physiological VDR ligand, and regulates various
      physiological processes, including calcium and bone metabolism, cellular growth
      and differentiation, immunity, and cardiovascular function. The secondary bile
      acid lithocholic acid, which is produced by intestinal bacteria, is another
      natural VDR ligand. Lithocholic acid stimulates xenobiotic metabolism and
      regulates immune and inflammatory responses via VDR, and its calcemic action is
      limited and observed only in vitamin D-deficient animals. Thus, lithocholic acid
      may be a function-selective VDR ligand. VDR is a promising drug in the treatment
      of bone and mineral disorders, cancer, autoimmune disease, inflammation, and
      cardiovascular disease. However, the adverse effect hypercalcemia limits wider
      clinical application of 1,25(OH)2D3 and its derivatives. Elucidation of the
      mechanism of VDR function by lithocholic acid should expand the possibility of
      VDR-targeted approaches.

PMID- 29074826
TI  - [Update on recent progress in vitamin D research. Molecular basis of epigenetic
      regulation by vitamin D via its nuclear receptor.]
AB  - Environment and structure of chromatin underlie epigenetics, and they also
      facilitate transcriptional regulations by nuclear receptors including VDR. In
      this short review, the molecular basis of chromatin remodeling and post
      translational modifications of histone proteins are illustrated with
      characterization of their regulators, providing mechanisms for co-regulation of
      epigenetics and transcription on chromatin. Moreover, the role of enhancer RNA
      (eRNA), one of the non-coding RNAs, in chromatin configuration is discussed for
      gene regulation by VDR.

PMID- 29074827
TI  - [Update on recent progress in vitamin D research. The effects of vitamin D in
      autoinflammatory diseases.]
AB  - Various kinds of immune cells -including dendritic cells, macrophages, T cells
      and B cells- express the vitamin D receptor and 1alpha-hydroxylase(CYP27B1). In
      vitro studies have shown the anti-inflammatory effect of 1,25-dihydroxyvitamin
      D:the active form of vitamin D. As vitamin D deficiency spread in our society,
      epidemiological studies have established the association between vitamin D
      deficiency and incidence or progression of several inflammatory diseases,
      including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and
      multiple sclerosis(MS). In addition, recently the property of vitamin D for
      treatment or prevention is debated. Here, we review the recent epidemiological
      evidence associated with vitamin D and inflammatory diseases, and describe the
      immunomodulatory effect of vitamin D underlying it.

PMID- 29074828
TI  - [Update on recent progress in vitamin D research. Vitamin D and metabolic
      disease.]
AB  - Numerous epidemiological studies and meta-analyses have indicated that there is a
      link between Vitamin D insufficiency/deficiency and metabolic disorders such as
      type 1 and type 2 diabetes mellitus as well as metabolic syndrome. However,
      vitamin D supplementation has not demonstrated improvement effects in obesity,
      disorders of glucose and lipid metabolism in any of these illnesses;therefore,
      the details of the causal relationship remain unclear. Improvement in glucose
      metabolism was observed in a study in which only vitamin D deficient patients
      with 25-hydroxyvitamin D[25(OH)D]levels of less than 20 ng/mL were given native
      vitamin D supplementation. Further studies are needed to determine the 25(OH)D
      level at which intervention is needed along with the required amount and duration
      of such supplementation.

PMID- 29074829
TI  - [Update on recent progress in vitamin D research. Vitamin D and muscle tissues.]
AB  - In elderly people, vitamin D insufficiency may increase the risk of fracture, and
      may also be involved in the development of sarcopenia or cardiovascular decline.
      Recent studies using vitamin D receptor knockout mice unveiled multiple functions
      of vitamin D beyond bone and mineral metabolism. This review describes the
      actions of vitamin D in skeletal, cardiac, and vascular smooth muscle.
      Eldecalcitol, an active vitamin D analog developed for the treatment of
      osteoporosis, also effectively improved skeletal muscle function in vivo, and may
      have synergistic activities in bone and muscle. Maintaining an optimal vitamin D
      status protects against fracture, and is expected to have beneficial effects for
      improving chronic diseases accompanied by muscle function abnormalities.

PMID- 29074830
TI  - [Update on recent progress in vitamin D research. Development of novel Vitamin D
      Derivatives.]
AB  - Vitamin D3 plays important roles in many physiological processes, including
      calcium and phosphate homeostasis, bone metabolism, and immune regulation. An
      active form of vitamin D3, 1alpha,25(OH)2D3, binds to vitamin D nuclear
      receptor(VDR, vitamin D receptor), and regulates expression of specific target
      genes. Thousands of vitamin D3 analogs have been synthesized, and the structure
      activity relationships of secosteroidal compounds have been examined in detail.
      On the other hand, development of non-secosteroidal VDR ligands remains limited,
      and only a few non-secosteroidal VDR ligands with potent activity have been
      reported so far. Development of novel structures with unique biological profiles
      would enable the new clinical application of vitamin D function.

PMID- 29074831
TI  - [Update on recent progress in vitamin D research. Eldecalcitol and intestinal
      calcium absorption.]
AB  - Though various physiological actions have been attributed to vitamin D, its most
      important function is to promote absorption of calcium from the intestinal tract.
      While the absorption rate of calcium is generally low, it tends to decline
      further with age. In addition, calcium intake is decreasing in recent years in
      Japan. Therefore, it is important to increase the intestinal calcium absorption
      rate. Eldecalcitol has been shown to increase calcium absorption from the
      intestinal tract, suppress bone resorption, increase bone mineral density, and
      prevent fractures. Elocalcitol use leads to a lower systemic active vitamin
      D[1alpha,25(OH)2D]concentration, compared to that with alfacalcidol use. This is
      because eldecalcitol inhibits vitamin D activation in the kidney. Therefore, it
      is presumed that the calcium absorption-boosting effect of eldecalcitol is not
      due to the action of 1alpha, 25(OH)2D, but due to eldecalcitol itself.

PMID- 29074832
TI  - [Update on recent progress in vitamin D research. EldecalcitolR and Fall
      Prevention.]
AB  - In the elderly, vitamin D deficiency results not only in impaired bone
      mineralization, but also myopathy. Low vitamin D has also been shown to be
      associated with decline of muscle strength, sarcopenia, functional limitation,
      and disability. Several recent studies have shown that low serum vitamin D
      concentration is associated with lower physical function and falls in older
      adults. In this article, the author reviews a relationship between falls and
      serum vitamin D concentration of the elderly living in the community, and also
      introduces the major results from a recent randomized controlled trial on
      prevention of decline of fall-related balance performance by the treatment with
      newly developed active vitamin D(EldecalcitolR )among the women with age 65 years
      old and over and diagnosed as osteoporosis.

PMID- 29074833
TI  - [Update on recent progress in vitamin D research. Vitamin D
      insufficiency/deficiency.]
AB  - Serum 25(OH)D level reflects bodily vitamin D store. Recently published
      "Assessment criteria for vitamin D deficiency/insufficiency in Japan" defines
      vitamin D sufficiency as 25(OH)D level of 30 ng/mL or more, vitamin D
      insufficiency as that of 20 to 30 ng/mL, vitamin D deficiency as that of less
      than 20 ng/mL. The lower the serum 25(OH)D level is, the higher the risks are, of
      secondary hyperparathyroidism, low bone mineral density, fall, fracture,
      rickets/osteomalacia, and hypocalcemia, as well as lower response to anti
      osteoporosis medications. Beyond musculoskeletal disorders, vitamin D
      insufficiency/deficiency has been shown to be associated with various
      immunological, metabolic, and malignant disorders mainly by basic and
      epidemiological studies.

PMID- 29074834
TI  - [Update on recent progress in vitamin D research. The role of vitamin D in
      management of CKD-MBD.]
AB  - Vitamin D was originally discovered as a substance which alleviates rickets and
      studies revealed that vitamin D exerts pleiotropic effects. Vitamin D has a
      therapeutic effect on Chronic Kidney Disease(CKD)-associated bone lesion or
      secondary hyperparathyroidism. On the other hand, excessive vitamin D induces
      calcium and phosphate overload, resulting in vascular calcification and
      cardiovascular events. From the data so far, not all CKD patients can get the
      benefit of vitamin D. It is well indicated for CKD patients with vitamin D
      insufficiency, secondary parathyroidism, hypocalcemia, or low-turnover bone
      disease on the basis of avoiding calcium over load.

PMID- 29074835
TI  - [Update on recent progress in vitamin D research. Treatment of metabolic bone
      disorders by vitamin D.]
AB  - Vitamin D is indispensable for bone health and calcium metabolism, and decreased
      action of vitamin D causes various abnormalities in bone metabolism. Severe
      vitamin D deficiency causes osteomalacia/rickets. Even milder vitamin D
      insufficiency could still be harmful for bone health via secondary
      hyperparathyroidism and bone loss, and could also lead to increased risk of
      falling. Osteomalacia/rickets associated with impaired vitamin D action should be
      treated by either native or active vitamin D3, depending on its etiology. As for
      osteoporosis, vitamin D repletion is important to adequate therapeutic effects of
      anti-resorptives. As a monotherapy, eldecalcitol, active vitamin D3 analogue, has
      been shown to increase bone mineral density and to decrease the incidence of
      vertebral fractures with significantly greater efficacy compared to active
      vitamin D3.

PMID- 29074837
TI  - [Update on recent progress in vitamin D research. Vitamin D in the treatment of
      psoriasis.]
AB  - Active vitamin D and analogs exert immunomodulatory effects and potent effects on
      cellular differentiation and proliferation in the skin. In the last few decades,
      it has convincingly been shown that these analogs are effective and safe in the
      topical treatment of psoriasis, where they nowadays represent a standard therapy.
      However, the mechanism of vitamin D action in the treatment of psoriasis remains
      largely unknown. Here, we reviewed and discussed the recent findings of molecular
      action of vitamin D in psoriasis.

PMID- 29074836
TI  - [Update on recent progress in vitamin D research. Vitamin D treatment for
      hypoparathyroidism.]
AB  - The patients with hypoparathyroidism have been treated with active vitamin D(ie,
      alfacalcidol and calcitriol). Parathyroid hormone(PTH)increases extracellular
      calcium concentration partly through the activation of vitamin D, and active
      vitamin D corrects hypocalcemia mainly by increasing intestinal calcium
      abosorption. PTH coordinately increases blood calcium level with vitamin D in
      bone and kidney, however, renal tubular reabsorption of calcium is regulated by
      PTH-dependent mechanism. Hypercalciuria is an complication of long-term vitamin D
      treatment for PTH-deficient hypoparathyroidism.

PMID- 29074838
TI  - [Genome editing ~Principle and possibility of a novel genetic engineering
      technology. Basic principles of genome editing.]
AB  - Programmable site-specific nuclease mediated-genome editing is an emerging
      biotechnology for precise manipulation of target genes. In genome editing, gene
      knockout as well as gene-knockin are possible in various organisms and cultured
      cells. CRISPR-Cas9, which was developed in 2012, is a convenient and efficient
      programmable site-specific nuclease and the use spreads around the world rapidly.
      For this, it is important for the progress of life science research to introduce
      the genome editing technology.

PMID- 29074839
TI  - Acute Onset Vascular Dementia with Bi-Thalamic Infarct in an HIV-Positive
      Subject.
AB  - BACKGROUND Bi-thalamic infarctions are rare and marked by clinical polymorphism.
      Their association with HIV has never been reported. CASE REPORT We report a 51
      year-old right-handed man with no medical history, who presented an acute onset
      vascular dementia associated with an antero-retrograde amnesia, a word-finding
      difficulty, and a dysexecutive syndrome. The CT scan was normal. Brain MRI
      revealed a paramedian and bi-thalamic infarction, evoking an occlusion of the
      Percheron artery. The electrocardiogram, transthoracic and transesophageal
      cardiac ultrasound, and Doppler echo of cervical arteries gave normal results.
      The biological work-up revealed a positive serology to HIV1. The patient was lost
      to follow-up and was reported dead 2 months later from an unknown cause.
      CONCLUSIONS This case illustrates the need to perform an HIV serology in the
      presence of a bi-thalamic infarction with no obvious cause, particularly in a
      young subject.

PMID- 29074840
TI  - Survey Regarding Attitude of Family About Organ Donation After Brain Death in
      Korea.
AB  - BACKGROUND This study examined the attitude of patients' relatives in South Korea
      toward organ donation after brain death. MATERIAL AND METHODS A structured
      questionnaire was used to obtain the information on the attitude toward organ
      donation for relatives of patients who were admitted to the surgical intensive
      care unit (SICU) between March 1, 2014 and September 30, 2016. In total, 92
      persons participated voluntarily. The investigation included general opinion
      about organ donation; and additional categorical analysis was performed. RESULTS
      In this study, 75% of participants agreed that they had positive thoughts on
      organ donation; however, fewer participants (60.9%) showed a positive attitude
      towards donating their own body, while only a third of participants (38.1%)
      agreed that they would donate relatives' body. We could confirm specifically
      concerns about excessive physical damage during organ recovery (34.7%) and
      ignorance or disrespect by hospital staff (15.2%), as well as consideration of
      being sacrificed for the benefit of others (26.0%). The participants who agreed
      to donate relatives' body showed significantly different responses in each
      categories of the questionnaire compared to the participants who disagreed or
      were undecided. CONCLUSIONS Despite positive perceptions concerning organ
      donation after brain death, there were nonetheless several prejudices and
      misunderstandings to overcome. The findings of this study can be used to
      establish evidence-based strategies.

PMID- 29074841
TI  - A Network Pharmacology Approach to Determine the Active Components and Potential
      Targets of Curculigo Orchioides in the Treatment of Osteoporosis.
AB  - BACKGROUND Osteoporosis is a complex bone disorder with a genetic predisposition,
      and is a cause of health problems worldwide. In China, Curculigo orchioides (CO)
      has been widely used as a herbal medicine in the prevention and treatment of
      osteoporosis. However, research on the mechanism of action of CO is still
      lacking. The aim of this study was to identify the absorbable components,
      potential targets, and associated treatment pathways of CO using a network
      pharmacology approach. MATERIAL AND METHODS We explored the chemical components
      of CO and used the five main principles of drug absorption to identify absorbable
      components. Targets for the therapeutic actions of CO were obtained from the
      PharmMapper server database. Pathway enrichment analysis was performed using the
      Comparative Toxicogenomics Database (CTD). Cytoscape was used to visualize the
      multiple components-multiple target-multiple pathways-multiple disease network
      for CO. RESULTS We identified 77 chemical components of CO, of which 32
      components could be absorbed in the blood. These potential active components of
      CO regulated 83 targets and affected 58 pathways. Data analysis showed that the
      genes for estrogen receptor alpha (ESR1) and beta (ESR2), and the gene for 11
      beta-hydroxysteroid dehydrogenase type 1, or cortisone reductase (HSD11B1) were
      the main targets of CO. Endocrine regulatory factors and factors regulating
      calcium reabsorption, steroid hormone biosynthesis, and metabolic pathways were
      related to these main targets and to ten corresponding compounds. CONCLUSIONS The
      network pharmacology approach used in our study has attempted to explain the
      mechanisms for the effects of CO in the prevention and treatment of osteoporosis,
      and provides an alternative approach to the investigation of the effects of this
      complex compound.

PMID- 29074842
TI  - Frequency selection rule for high definition and high frame rate Lissajous
      scanning.
AB  - Lissajous microscanners are very attractive in compact laser scanning
      applications such as endomicroscopy or pro-projection display owing to high
      mechanical stability and low operating voltages. The scanning frequency serves as
      a critical factor for determining the scanning imaging quality. Here we report
      the selection rule of scanning frequencies that can realize high definition and
      high frame-rate (HDHF) full-repeated Lissajous scanning imaging. The fill factor
      (FF) monotonically increases with the total lobe number of a Lissajous curve,
      i.e., the sum of scanning frequencies divided by the great common divisor (GCD)
      of bi-axial scanning frequencies. The frames per second (FPS), called the pattern
      repeated rate or the frame rate, linearly increases with GCD. HDHF Lissajous
      scanning is achieved at the bi-axial scanning frequencies, where the GCD has the
      maximum value among various sets of the scanning frequencies satisfying the total
      lobe number for a target FF. Based on this selection rule, the experimental
      results clearly demonstrate that conventional Lissajous scanners substantially
      increase both FF and FPS by slightly modulating the scanning frequencies at near
      the resonance within the resonance bandwidth of a Lissajous scanner. This
      selection rule provides a new guideline for HDHF Lissajous scanning in compact
      laser scanning systems.

PMID- 29074843
TI  - A Quantitative Point-of-Need Assay for the Assessment of Vitamin D3 Deficiency.
AB  - Vitamin D is necessary for the healthy growth and development of bone and muscle.
      Vitamin D deficiency, which is present in 42% of the US population, is often
      undiagnosed as symptoms may not manifest for several years and long-term
      deficiency has been linked to osteoporosis, diabetes and cancer. Currently the
      majority of vitamin D testing is performed in large-scale commercial laboratories
      which have high operational costs and long times-to-result. Development of a low
      cost point-of-need assay could be transformative to deficiency analysis in
      limited-resource settings. The best biomarker of vitamin D status,
      25hydroxyvitamin D3 (25(OH)D3), however, is particularly challenging to measure
      in such a format due to complexities involved in sample preparation, including
      the need to separate the marker from its binding protein. Here we present a rapid
      diagnostic test for the accurate, quantitative assessment of 25(OH)D3 in finger
      stick blood. The assay is accompanied by a smartphone-assisted portable imaging
      device that can autonomously perform the necessary image processing. To achieve
      accurate quantification of 25(OH)D3, we also demonstrate a novel elution buffer
      that separates 25(OH)D3 from its binding protein in situ, eliminating the need
      for sample preparation. In human trials, the accuracy of our platform is 90.5%.

PMID- 29074844
TI  - Limiting habenular hyperactivity ameliorates maternal separation-driven
      depressive-like symptoms.
AB  - Early-life stress, including maternal separation (MS), increases the
      vulnerability to develop mood disorders later in life, but the underlying
      mechanisms remain elusive. We report that MS promotes depressive-like symptoms in
      mice at a mature stage of life. Along with this behavioral phenotype, MS drives
      reduction of GABAB-GIRK signaling and the subsequent lateral habenula (LHb)
      hyperexcitability-an anatomical substrate devoted to aversive encoding.
      Attenuating LHb hyperactivity using chemogenetic tools and deep-brain stimulation
      ameliorates MS depressive-like symptoms. This provides insights on mechanisms and
      strategies to alleviate stress-dependent affective behaviors.

PMID- 29074846
TI  - A method for the unbiased and efficient segmental labelling of RNA-binding
      proteins for structure and biophysics.
AB  - Most eukaryotic RNA regulators recognise their RNA and protein partners by the
      combinatorial use of several RNA binding domains. Inter-domain dynamics and
      interactions play a key role in recognition and can be analysed by techniques
      such as NMR or FRET, provided that the information relative to the individual
      interactions can be de-convoluted. Segmentally labelling the proteins by ligating
      labelled and unlabelled peptide chains allows one to filter out unwanted
      information and observe the labelled moieties only. Several strategies have been
      implemented to ligate two protein fragments, but multiple ligations, which are
      necessary to segmentally label proteins of more than two domains, are more
      challenging and often dependent on the structure and solubility of the domains.
      Here we report a method to ligate multiple protein segments that allows the fast,
      high yield labelling of both internal and end domains, depending on the
      requirements. We use TCEP and mercaptophenylacetic acid (MPAA) in an optimised
      reaction environment to achieve an efficient ligation of protein domains
      independently from their structure or solubility. We expect the method will
      provide a useful tool for the molecular study of combinatorial protein-RNA
      recognition in RNA regulation.

PMID- 29074845
TI  - Connexin 43 Hemichannels Regulate the Expression of Wound Healing-Associated
      Genes in Human Gingival Fibroblasts.
AB  - Connexin 43 (Cx43) is the most ubiquitous connexin in various cells, and presents
      as hemichannels (HCs) and gap junctions (GJs) on the cell membrane. We have
      recently shown that Cx43 abundance was strongly reduced in fibroblasts of human
      gingival wounds, and blocking Cx43 function in cultured human gingival
      fibroblasts (GFBLs) strongly regulated the expression of wound healing-related
      genes. However, it is not known whether these responses involved Cx43 HCs or GJs.
      Here we show that Cx43 assembled into distinct GJ and HC plaques in GFBLs both in
      vivo and in vitro. Specific blockage of Cx43 HC function by TAT-Gap19, a Cx43
      mimetic peptide, significantly upregulated the expression of several MMPs, TGF
      beta signaling molecules, Tenascin- C, and VEGF-A, while pro-fibrotic molecules,
      including several extracellular matrix proteins and myofibroblast and cell
      contractility-related molecules, were significantly downregulated. These changes
      were linked with TAT-Gap19-induced suppression of ATP signaling and activation of
      the ERK1/2 signaling pathway. Collectively, our data suggest that reduced Cx43 HC
      function could promote fast and scarless gingival wound healing. Thus, selective
      suppression of Cx43 HCs may provide a novel target to modulate wound healing.

PMID- 29074847
TI  - Recommendation for incorporation of a different lymph node scoring system in
      future AJCC N category for oral cancer.
AB  - To compare the prognostic value of 3 different lymph node scoring systems " log
      odds of positive nodes (LODDS), lymph node ratio (rN), and lymph node yield " in
      an effort to improve the staging of oral cancer. We identified 3958 oral cancer
      patients from Surveillance, Epidemiology, and End Results database from 2007 to
      2013. In univariate analysis, LODDS, pN, rN, and lymph node yield were prognostic
      factors for 5-year disease-specific survival (DSS) and overall survival (OS).
      Multivariate analysis indicated that patients with LODDS 4 had worst 5-year DSS
      and OS. Stage migration occurred in pN1 and pN2 patients with LODDS 4. In pN1
      patients, those with LODDS 4 had the worst 5-year DSS (41.2%) and OS (31.6%) than
      patients with pN1 and LODDS 2-3. In pN2 patients, those with LODDS4 had the worst
      5-year DSS (34.5%) and OS (27.4%) than patients with pN2 and LODDS 2-3. The
      proposed staging system, which incorporates LODDS with AJCC pN, had better
      discriminability and prediction accuracy for predicting survival. We also noted
      that patients with LODDS 4 given adjuvant radiotherapy had better 5-year DSS and
      OS. The LODDS should be considered as a future candidate measurement for N
      category in oral cancer.

PMID- 29074848
TI  - Acridine orange exhibits photodamage in human bladder cancer cells under blue
      light exposure.
AB  - Human bladder cancer (BC) cells exhibit a high basal level of autophagic activity
      with accumulation of acridine-orange(AO)-stained acidic vesicular organelles. The
      rapid AO relocalization was observed in treated BC cells under blue-light
      emission. To investigate the cytotoxic effects of AO on human BC cell lines under
      blue-light exposure, human immortalized uroepithelial (SV-Huc-1) and BC cell
      lines (5637 and T24) were treated with indicated concentrations of AO or blue
      light exposure alone and in combination. The cell viability was then determined
      using WST-1, time-lapse imaging with a Cytosmart System and continuous
      quantification with a multi-mode image-based reader. Treatment of AO or blue
      light exposure alone did not cause a significant loss of viability in BC cells.
      However, AO exhibited a dose-dependent increment of cytotoxicity toward BC cells
      under blue-light exposure. Furthermore, the tumor formation of BC cells with
      treatment was significantly reduced when evaluated in a mouse xenograft model.
      The photodamage caused by AO was nearly neglected in SV-Huc-1 cells, suggesting a
      differential effect of this treatment between cancer and normal cells. In
      summary, AO, as a photosensitizer, disrupts acidic organelles and induces cancer
      cell death in BC cells under blue-light irradiation. Our findings may serve as a
      novel therapeutic strategy against human BC.

PMID- 29074849
TI  - The circular RNA circBIRC6 participates in the molecular circuitry controlling
      human pluripotency.
AB  - Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the
      human transcriptome. However, their involvement in biological processes,
      including pluripotency, remains mostly undescribed. We identified a subset of
      circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs)
      and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated
      with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched
      in the AGO2 complex and directly interacts with microRNAs, miR-34a, and miR-145,
      which are known to modulate target genes that maintain pluripotency.
      Correspondingly, circBIRC6 attenuates the downregulation of these target genes
      and suppresses hESC differentiation. We further identified hESC-enriched splicing
      factors (SFs) and demonstrated that circBIRC6 biogenesis in hESCs is promoted by
      the SF ESRP1, whose expression is controlled by the core pluripotency-associated
      factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a
      microRNA "sponge" to regulate the molecular circuitry, which modulates human
      pluripotency and differentiation.

PMID- 29074850
TI  - Bisphenol A in eggs causes development-specific liver molecular reprogramming in
      two generations of rainbow trout.
AB  - Bisphenol A (BPA) is widely used in the manufacture of plastics and epoxy resins
      and is prevalent in the aquatic environment. BPA disrupts endocrine pathways in
      fish, but the long-term developmental implications are unknown. We demonstrate
      that BPA deposition in the eggs of rainbow trout (Oncorhynchus mykiss), an
      ecologically and economically important species of fish, reprograms liver
      metabolism in the offspring and alters the developmental growth trajectory in two
      generations. Specifically, BPA reduces growth during early development, followed
      by a catch-up growth post-juveniles. More importantly, we observed a
      developmental shift in the liver transcriptome, including an increased propensity
      for protein breakdown during early life stages to lipid and cholesterol synthesis
      post- juveniles. The liver molecular responses corresponded with the transient
      growth phenotypes observed in the F1 generation, and this was also evident in the
      F2 generation. Altogether, maternal and/or ancestral embryonic exposure to BPA
      affects liver metabolism leading to development-distinct effects on growth,
      underscoring the need for novel risk assessment strategies for this chemical in
      the aquatic environment. This is particularly applicable to migratory species,
      such as salmon, where distinct temporal changes in growth and physiology during
      development are critical for their spawning success.

PMID- 29074851
TI  - Preparing entangled states between two NV centers via the damping of
      nanomechanical resonators.
AB  - We propose an efficient scheme for preparing entangled states between two
      separated nitrogen-vacancy (NV) centers in a spin-mechanical system via a
      dissipative quantum dynamical process. The proposal actively exploits the
      nanomechanical resonator (NAMR) damping to drive the NV centers to the target
      state through a quantum reservoir engineering approach. The distinct features of
      the present work are that we turn the detrimental source of noise into a resource
      and only need high-frequency low-Q mechanical resonators, which make our scheme
      more simple and feasible in experimental implementation. This protocol may have
      interesting applications in quantum information processing with spin-mechanical
      systems.

PMID- 29074852
TI  - Improved performance of the artus Mycobacterium tuberculosis RG PCR kit in a low
      incidence setting: a retrospective monocentric study.
AB  - Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC)
      strains resistant against rifampin (RIF) and isoniazid (INH) pose a serious
      threat to global health. However, rapid and reliable MTBC detection along with
      RIF/INH susceptibility testing are challenging in low prevalence countries due to
      the higher rate of false positives. Here, we provide the first performance data
      for the artus MTBC PCR assay in a low prevalence setting. We analyze 1323
      respiratory and 311 non-respiratory samples with the artus MTBC PCR assay as well
      as by mycobacterial culture and microscopy. We propose retesting of specimens in
      duplicate and consideration of a determined cycle-threshold value cut-off greater
      than 34, as this significantly increases accuracy, specificity, and negative
      predictive value without affecting sensitivity. Furthermore, we tested fourteen
      MTBC positive samples with the GenoType MTBDRplus test and demonstrate that using
      an identical DNA extraction protocol for both assays does not impair downstream
      genotypic testing for RIF and INH susceptibility. In conclusion, our procedure
      optimizes the use of the artus MTB assay with workload efficient methods in a low
      incidence setting. Combining the modified artus MTB with the GenoType MTBDRplus
      assays allows rapid and accurate detection of MTBC and RIF/INH resistance.

PMID- 29074853
TI  - Determining the Quality Factor of Dielectric Ceramic Mixtures with Dielectric
      Constants in the Microwave Frequency Range.
AB  - Microwave dielectric ceramic materials are extensively utilized in microwave
      applications because of their high dielectric constants and quality factors.
      These applications also require ceramics of zero temperature coefficients at the
      resonant frequency (tau f ), which can be realized through mixing a ceramic that
      one is interested in with another ceramic with -tau f , or by performing the
      ionic substitution. With the mixing/ionic substitution, it is indispensable to
      compute the quality factors precisely. Previous study indicates that the quality
      factor depends on the grain size, porosity, internal strain, structure, phase
      evolution, and conductivity etc. Here we derive a quality factor formula based on
      the definition, which works very well for multiphase composites, single phase
      solid solutions, and equivalent ionic substituted single phase materials. Our
      formula calculation and fits to the previous experimental results demonstrate
      that the quality factor of the ceramic mixtures strongly depend on the dielectric
      constants and the dielectric constant variation index. Our results suggest that
      the impacts from grain size, porosity, and internal strain etc. can be summarized
      to the dielectric constant or dielectric constant variation index, which is of
      great importance for future design of high performance microwave dielectric
      ceramics.

PMID- 29074855
TI  - Enhanced conversion efficiency in Si solar cells employing photoluminescent down
      shifting CdSe/CdS core/shell quantum dots.
AB  - Silicon solar cells have captured a large portion of the total market of
      photovoltaic devices mostly due to their relatively high efficiency. However,
      Silicon exhibits limitations in ultraviolet absorption because high-energy
      photons are absorbed at the surface of the solar cell, in the heavily doped
      region, and the photo-generated electron-hole pairs need to diffuse into the
      junction region, resulting in significant carrier recombination. One of the
      alternatives to improve the absorption range involves the use of down-shifting
      nano-structures able to interact with the aforementioned high energy photons.
      Here, as a proof of concept, we use downshifting CdSe/CdS quantum dots to improve
      the performance of a silicon solar cell. The incorporation of these
      nanostructures triggered improvements in the short circuit current density (Jsc,
      from 32.5 to 37.0 mA/cm2). This improvement led to a ~13% increase in the power
      conversion efficiency (PCE), from 12.0 to 13.5%. Our results demonstrate that the
      application of down-shifting materials is a viable strategy to improve the
      efficiency of Silicon solar cells with mass-compatible techniques that could
      serve to promote their widespread utilization.

PMID- 29074854
TI  - Gag P2/NC and pol genetic diversity, polymorphism, and drug resistance mutations
      in HIV-1 CRF02_AG- and non-CRF02_AG-infected patients in Yaounde, Cameroon.
AB  - In HIV-1 subtype-B, specific mutations in Gag cleavage sites (CS) are associated
      with treatment failure, with limited knowledge among non-B subtypes. We analyzed
      non-B HIV-1 gag and pol (protease/reverse-transcriptase) sequences from
      Cameroonians for drug resistance mutations (DRMs) in the gag P2/NC CS, and pol
      major DRMs. Phylogeny of the 141 sequences revealed a high genetic diversity (12
      subtypes): 67.37% CRF02_AG versus 32.6% non-CRF02_AG. Overall, 7.3% transmitted
      and 34.3% acquired DRMs were found, including M184V, thymidine analogue mutations
      (T215F, D67N, K70R, K219Q), NNRTIs (L100I, Y181C, K103N, V108I, Y188L), and PIs
      (V82L). Twelve subjects [10 with HIV-1 CRF02_AG, 8 treatment-naive and 4 on 3TC
      AZT-NVP] showed 3 to 4 mutations in the Gag P2/NC CS: S373Q/T/A, A374T/S/G/N,
      T375S/A/N/G, I376V, G381S, and R380K. Subjects with or without Gag P2/NC CS
      mutations showed no significant difference in viral loads. Treatment-naive
      subjects harboring NRTI-DRMs had significantly lower CD4 cells than those with
      NRTI-DRMs on ART (p = 0.042). Interestingly, two subjects had major DRMs to
      NRTIs, NNRTIs, and 4 mutations in the Gag P2/NC CS. In this prevailing CRF02_AG
      population with little exposure to PIs (~3%), mutations in the Gag P2/NC CS could
      increase the risk of treatment failure if there is increased use of PIs-based
      therapy.

PMID- 29074856
TI  - Engineering a synthetic pathway for maleate in Escherichia coli.
AB  - Maleate is one of the most important dicarboxylic acids and is used to produce
      various polymer compounds and pharmaceuticals. Herein, microbial production of
      maleate is successfully achieved, to our knowledge for the first time, using
      genetically modified Escherichia coli. A synthetic pathway of maleate is
      constructed in E. coli by combining the polyketide biosynthesis pathway and
      benzene ring cleavage pathway. The metabolic engineering approach used to fine
      tune the synthetic pathway drastically improves maleate production and
      demonstrates that one of the rate limiting steps exists in the conversion of
      chorismate to gentisate. In a batch culture of the optimised transformant, grown
      in a 1-L jar fermentor, the amount of produced maleate reaches 7.1 g L-1, and the
      yield is 0.221 mol mol-1. Our results suggest that the construction of synthetic
      pathways by combining a secondary metabolite pathway and the benzene ring
      cleavage pathway is a powerful tool for producing various valuable chemicals.

PMID- 29074858
TI  - High fat diet exacerbates murine psoriatic dermatitis by increasing the number of
      IL-17-producing gammadelta T cells.
AB  - Psoriasis is a common, chronic inflammatory skin disease characterized by
      epidermal hyperplasia via the IL-23/IL-17 axis. Various studies have indicated
      the association between obesity and psoriasis, however, the underlying mechanisms
      remains unclarified. To this end, we focused on high-fat diet (HFD) in this
      study, because HFD is suggested as a contributor to obesity, and HFD-fed mice
      exhibit exacerbated psoriatic dermatitis. Using murine imiquimod (IMQ)-induced
      psoriasis and HFD-induced obesity models, we have revealed a novel mechanism of
      HFD-induced exacerbation of psoriatic dermatitis. HFD-fed mice exhibited
      aggravated psoriatic dermatitis, which was accompanied with increased
      accumulation of IL-17A-producing Vgamma4+ gammadelta T cells in the skin. HFD
      also induced the increase of Vgamma4+ gammadelta T cells in other organs such as
      skin draining lymph nodes, which preceded the increase of them in the skin. In
      addition, HFD-fed mice displayed increased expression of several gammadelta T
      cell-recruiting chemokines in the skin. On the other hand, ob/ob mice, another
      model of murine obesity on normal diet, did not exhibit aggravated psoriatic
      dermatitis nor accumulation of gammadelta T cells in the dermis. These results
      indicate that HFD is a key element in exacerbation of IMQ-induced psoriatic
      dermatitis, and further raise the possibility of HFD as a factor that links
      obesity and psoriasis.

PMID- 29074857
TI  - Methods to Evaluate Cell Growth, Viability, and Response to Treatment in a Tissue
      Engineered Breast Cancer Model.
AB  - The use of in vitro, engineered surrogates in the field of cancer research is of
      interest for studies involving mechanisms of growth and metastasis, and response
      to therapeutic intervention. While biomimetic surrogates better model human
      disease, their complex composition and dimensionality make them challenging to
      evaluate in a real-time manner. This feature has hindered the broad
      implementation of these models, particularly in drug discovery. Herein, several
      methods and approaches for the real-time, non-invasive analysis of cell growth
      and response to treatment in tissue-engineered, three-dimensional models of
      breast cancer are presented. The tissue-engineered surrogates used to demonstrate
      these methods consist of breast cancer epithelial cells and fibroblasts within a
      three dimensional volume of extracellular matrix and are continuously perfused
      with nutrients via a bioreactor system. Growth of the surrogates over time was
      measured using optical in vivo (IVIS) imaging. Morphologic changes in specific
      cell populations were evaluated by multi-photon confocal microscopy. Response of
      the surrogates to treatment with paclitaxel was measured by optical imaging and
      by analysis of lactate dehydrogenase and caspase-cleaved cytokeratin 18 in the
      perfused medium. Each method described can be repeatedly performed during
      culture, allowing for real-time, longitudinal analysis of cell populations within
      engineered tumor models.

PMID- 29074859
TI  - The characteristics of adjacent anatomy of mandibular third molar germs: a CBCT
      study to assess the risk of extraction.
AB  - This study aims to investigate the characteristics of adjacent anatomy of
      mandibular third molar germs (MTMGs). Three hundred Chinese patients aged 12 to
      17 years old who received cone-beam computed tomography (CBCT) were enrolled. The
      continuity of cortical outline of inferior alveolar canals (IACs) in the region
      of MTMGs, the integrity of lingual bone cortex and the relationship between hard
      tissue part of MTMGs and IACs were investigated by observing CBCT data via the
      NNT viewer software. The age, degree of dental development, gender and location
      were recorded as variables. The associations between different variables and the
      observed data were analysed. The possibilities of disrupted cortical outline of
      IACs or the hard tissue part of MTMGs contacting IACs were significantly lower in
      12 or 13 age groups, lower in Nolla stage <= 6. Males were significantly less
      than females in the incidence of disrupted cortical outline of IACs. As to the
      perforation of lingual bone cortex, no significant differences were observed in
      gender, ages, location or development stages. According to the CBCT images,
      anatomical factors contributed the lest to the risk of inferior alveolar nerve
      and lingual nerve injury in the 12 to 13 age group during removing the MTMG
      removal.

PMID- 29074860
TI  - Steroid hormone profiling in obese and nonobese women with polycystic ovary
      syndrome.
AB  - The study explored differences in the steroidogenic pathway between obese and
      nonobese women with polycystic ovary syndrome (PCOS) using liquid chromatography
      tandem mass spectrometry (LC-MS/MS). 1044 women with PCOS (including 350 lean,
      312 overweight and 382 obese) and 366 control women without PCOS (including 203
      lean, 32 overweight and 131 obese) were enrolled. The differences in steroid
      hormones were amplified in lean PCOS versus lean controls compared with obese
      PCOS versus obese controls. Compared with obese PCOS, lean PCOS demonstrated
      increased dehydroepiandrosterone sulfate (P = 0.015), 17-hydropregnenolone (P =
      0.003), 17-hydroprogesterone (17-OHP) (P < 0.001), progesterone (P < 0.001) and
      estrone (P < 0.001) levels. Enzyme activity evaluation showed that lean PCOS had
      increased activity of P450c17 (17-hydropregnenolone/pregnenolone, P < 0.001),
      P450aro (P < 0.001), 3betaHSD2 (progesterone/ pregnenolone and 17-OHP/17
      hydropregnenolone, both P < 0.001) and decreased activity of P450c21(11
      deoxycorticorsterone/progesterone and 11-deoxycortisol/17-OHP, P < 0.001).
      Moreover, we found higher frequencies of CYP21A2- (encoding P450c21) c.552 C > G
      (p. D184E) in lean PCOS compared with obese PCOS patients (P = 0.006). In
      conclusion, this study demonstrated for the first time that the adrenal-specific
      enzyme P450c21 showed decreased activity in lean PCOS patients, and that the
      adrenal androgen excess may play different roles in lean and obese PCOS patients,
      which represents as different enzyme activity in the steroidogenic pathway.

PMID- 29074862
TI  - Bacteria-inspired nanorobots with flagellar polymorphic transformations and
      bundling.
AB  - Wirelessly controlled nanoscale robots have the potential to be used for both in
      vitro and in vivo biomedical applications. So far, the vast majority of reported
      micro- and nanoscale swimmers have taken the approach of mimicking the rotary
      motion of helical bacterial flagella for propulsion, and are often composed of
      monolithic inorganic materials or photoactive polymers. However, currently no man
      made soft nanohelix has the ability to rapidly reconfigure its geometry in
      response to multiple forms of environmental stimuli, which has the potential to
      enhance motility in tortuous heterogeneous biological environments. Here, we
      report magnetic actuation of self-assembled bacterial flagellar nanorobotic
      swimmers. Bacterial flagella change their helical form in response to
      environmental stimuli, leading to a difference in propulsion before and after the
      change in flagellar form. We experimentally and numerically characterize this
      response by studying the swimming of three flagellar forms. Also, we demonstrate
      the ability to steer these devices and induce flagellar bundling in multi
      flagellated nanoswimmers.

PMID- 29074861
TI  - Sulforaphane reactivates cellular antioxidant defense by inducing Nrf2/ARE/Prdx6
      activity during aging and oxidative stress.
AB  - Upon oxidative stress and aging, Nrf2 (NFE2-related factor2) triggers antioxidant
      defense genes to defends against homeostatic failure. Using human(h) or rat(r)
      lens epithelial cells (LECs) and aging human lenses, we showed that a progressive
      increase in oxidative load during aging was linked to a decline in Prdx6
      expression. DNA binding experiments using gel-shift and ChIP assays demonstrated
      a progressive reduction in Nrf2/ARE binding (-357/-349) of Prdx6 promoter. The
      promoter (-918) with ARE showed a marked reduction in young vs aged hLECs, which
      was directly correlated to decreased Nrf2/ARE binding. A Nrf2 activator,
      Sulforaphane (SFN), augmented Prdx6, catalase and GSTpi expression in dose
      dependent fashion, and halted Nrf2 dysregulation of these antioxidants. SFN
      reinforced Nrf2/DNA binding and increased promoter activities by enhancing
      expression and facilitating Nrf2 translocalization in nucleus. Conversely,
      promoter mutated at ARE site did not respond to SFN, validating the SFN-mediated
      restoration of Nrf2/ARE signaling. Furthermore, SFN rescued cells from UVB
      induced toxicity in dose-dependent fashion, which was consistent with SFN's dose
      dependent activation of Nrf2/ARE interaction. Importantly, knockdown of Prdx6
      revealed that Prdx6 expression was prerequisite for SFN-mediated cytoprotection.
      Collectively, our results suggest that loss of Prdx6 caused by dysregulation of
      ARE/Nrf2 can be attenuated through a SFN, to combat diseases associated with
      aging.

PMID- 29074863
TI  - Cross-plane Thermoelectric and Thermionic Transport across Au/h-BN/Graphene
      Heterostructures.
AB  - The thermoelectric voltage generated at an atomically abrupt interface has not
      been studied exclusively because of the lack of established measurement tools and
      techniques. Atomically thin 2D materials provide an excellent platform for
      studying the thermoelectric transport at these interfaces. Here, we report a
      novel technique and device structure to probe the thermoelectric transport across
      Au/h-BN/graphene heterostructures. An indium tin oxide (ITO) transparent
      electrical heater is patterned on top of this heterostructure, enabling Raman
      spectroscopy and thermometry to be obtained from the graphene top electrode in
      situ under device operating conditions. Here, an AC voltage V(omega) is applied
      to the ITO heater and the thermoelectric voltage across the Au/h-BN/graphene
      heterostructure is measured at 2omega using a lock-in amplifier. We report the
      Seebeck coefficient for our thermoelectric structure to be -215 MUV/K. The
      Au/graphene/h-BN heterostructures enable us to explore thermoelectric and thermal
      transport on nanometer length scales in a regime of extremely short length
      scales. The thermoelectric voltage generated at the graphene/h-BN interface is
      due to thermionic emission rather than bulk diffusive transport. As such, this
      should be thought of as an interfacial Seebeck coefficient rather than a Seebeck
      coefficient of the constituent materials.

PMID- 29074864
TI  - Prolonged duration of nonequilibrated Dirac fermions in neutral topological
      insulators.
AB  - Topological insulators (TIs) possess spin-polarized Dirac fermions on their
      surface but their unique properties are often masked by residual carriers in the
      bulk. Recently, (Sb1-x Bi x )2Te3 was introduced as a non-metallic TI whose
      carrier type can be tuned from n to p across the charge neutrality point. By
      using time- and angle-resolved photoemission spectroscopy, we investigate the
      ultrafast carrier dynamics in the series of (Sb1-x Bi x )2Te3. The Dirac
      electronic recovery of ~10 ps at most in the bulk-metallic regime elongated to
      >400 ps when the charge neutrality point was approached. The prolonged
      nonequilibration is attributed to the closeness of the Fermi level to the Dirac
      point and to the high insulation of the bulk. We also discuss the feasibility of
      observing excitonic instability of (Sb1-x Bi x )2Te3.

PMID- 29074865
TI  - Tuning a sign of magnetoelectric coupling in paramagnetic NH2(CH3)2Al1-xCrx(SO4)2
      * 6H2O crystals by metal ion substitution.
AB  - Hybrid organometallic systems offer a wide range of functionalities, including
      magnetoelectric (ME) interactions. However, the ability to design on-demand ME
      coupling remains challenging despite a variety of host-guest configurations and
      ME phases coexistence possibilities. Here, we report the effect of metal-ion
      substitution on the magnetic and electric properties in the paramagnetic
      ferroelectric NH2(CH3)2Al1-x Cr x (SO4)2 * 6H2O. Doing so we are able to induce
      and even tune a sign of the ME interactions, in the paramagnetic ferroelectric
      (FE) state. Both studied samples with x = 0.065 and x = 0.2 become paramagnetic,
      contrary to the initial diamagnetic compound. Due to the isomorphous substitution
      with Cr the ferroelectric phase transition temperature (T c ) increases
      nonlinearly, with the shift being larger for the 6.5% of Cr. A magnetic field
      applied along the polar c axis increases ferroelectricity for the x = 0.065
      sample and shifts T c to higher values, while inverse effects are observed for x
      = 0.2. The ME coupling coefficient alphaME = 1.7 ns/m found for a crystal with Cr
      content of x = 0.2 is among the highest reported up to now. The observed sign
      change of alphaME with a small change in Cr content paves the way for ME coupling
      engineering.

PMID- 29074866
TI  - Activation of PKA in cell requires higher concentration of cAMP than in vitro:
      implications for compartmentalization of cAMP signalling.
AB  - cAMP is a ubiquitous second messenger responsible for the cellular effects of
      multiple hormones and neurotransmitters via activation of its main effector,
      protein kinase A (PKA). Multiple studies have shown that the basal concentration
      of cAMP in several cell types is about 1 MUM. This value is well above the
      reported concentration of cAMP required to half-maximally activate PKA, which
      measures in the 100-300 nM range. Several hypotheses have been suggested to
      explain this apparent discrepancy including inaccurate measurements of
      intracellular free cAMP, inaccurate measurement of the apparent activation
      constant of PKA or shielding of PKA from bulk cytosolic cAMP via localization of
      the enzyme to microdomains with lower basal cAMP concentration. However, direct
      experimental evidence in support of any of these models is limited and a firm
      conclusion is missing. In this study we use multiple FRET-based reporters for the
      detection of cAMP and PKA activity in intact cells and we establish that the
      sensitivity of PKA to cAMP is almost twenty times lower when measured in cell
      than when measured in vitro. Our findings have important implications for the
      understanding of compartmentalized cAMP signalling.

PMID- 29074867
TI  - Removal of cationic and anionic heavy metals from water by 1D and 2D-carbon
      structures decorated with magnetic nanoparticles.
AB  - In this study, cobalt ferrites (C) decorated onto 2D material (porous graphene
      (PG)) and 1D material (carbon nanofibers (CNF)), denoted as PG-C and CNF-C
      nanocomposites, respectively, were synthesized using solvothermal process. The
      prepared nanocomposites were studied as magnetic adsorbents for the removal of
      lead (cationic) and chromium(VI) (anionic) metal ions. The structural and
      chemical analysis of synthesized nanocomposites was conducted using different
      characterization techniques including Brunauer-Emmett-Teller (BET) analysis,
      field emission-scanning electron microscopy (FE-SEM), Fourier-transform infrared
      spectroscopy (FTIR), high resolution-transmission electron microscopy (HR-TEM),
      vibrating sample magnetometer (VSM), X-ray diffraction (XRD), and X-ray
      photoelectron spectroscopy (XPS). Batch mode adsorption studies were conducted
      with the prepared nanocomposites to examine their maximum adsorption potential
      for lead and chromate ions. Performance parameters (time, pH, adsorbent dosage
      and initial ion concentrations) effecting the adsorption capacity of the
      nanocomposites were optimized. Different kinetic and isotherm models were
      examined to elucidate the adsorption process. Synthesized nanocomposites
      exhibited significant potential for the studied metal ions that can be further
      examined at pilot scale for the removal of metal ions from contaminated water.

PMID- 29074868
TI  - Lateralized occipito-temporal N1 responses to images of salient distorted finger
      postures.
AB  - For humans as social beings, other people's hands are highly visually
      conspicuous. Exceptionally striking are hands in other than natural configuration
      which have been found to elicit distinct brain activation. Here we studied
      response strength and lateralization of this activation using event-related
      potentials (ERPs), in particular, occipito-temporal N1 responses as correlates of
      activation in extrastriate body area. Participants viewed computer-generated
      images of hands, half of them showing distorted fingers, the other half showing
      natural fingers. As control stimuli of similar geometric complexity, images of
      chairs were shown, half of them with distorted legs, half with standard legs. The
      contrast of interest was between distorted and natural/standard stimuli. For
      hands, stronger N1 responses were observed for distorted (vs natural) stimuli
      from 170 ms post stimulus. Such stronger N1 responses were found for distorted
      hands and absent for distorted chairs, therefore likely unrelated to visuospatial
      processing of the unusual distorted shapes. Rather, N1 modulation over both
      hemispheres - but robustly right-lateralized - could reflect distorted hands as
      emotionally laden stimuli. The results are in line with privileged visual
      processing of hands as highly salient body parts, with distortions engaging
      neural resources that are especially activated for biological stimuli in social
      perception.

PMID- 29074869
TI  - Effects of crop load on distribution and utilization of 13C and 15N and fruit
      quality for dwarf apple trees.
AB  - In order to define the effects of fruit crop load on the distribution and
      utilization of carbon and nitrogen in dwarf apple trees, we conducted three crop
      load levels (High-crop load, 6 fruits per trunk cross-sectional area (cm2, TCA)),
      Medium-crop load (4 fruits cm-2 TCA), Low-crop load (2 fruits cm-2 TCA)) in 2014
      and 2015. The results indicated that the 15N derived from fertilizer (Ndff)
      values of fruits decreased with the reduction of crop load, but the Ndff values
      of annual branches, leaves and roots increased. The plant 15N-urea utilization
      rates on Medium and Low-crop load were 1.12-1.35 times higher than the High-crop
      load. With the reduction of crop load, the distribution rate of 13C and 15N in
      fruits was gradually reduced, but in contrast, the distribution of 13C and 15N
      gradually increased in annual branches, leaves and roots. Compared with High-crop
      load, the Medium and Low-crop load significantly improved fruit quality p < 0.05.
      Hence, controlling fruit load effectively regulated the distribution of carbon
      and nitrogen in plants, improved the nitrogen utilization rate and fruit quality.
      The appropriate crop load level for mature M.26 interstocks apple orchards was
      deemed to be 4.0 fruits cm-2 TCA.

PMID- 29074870
TI  - Nonlinear magnetoelectric effect in paraelectric state of Co4Nb2O9 single
      crystal.
AB  - We report the structural, magnetoelectric (ME), magnetic and electric control of
      magnetic properties in Co4Nb2O9 (CNO) single crystal. A detailed ME measurement
      reveals a nonlinear ME effect instead of a linear ME effect in CNO single
      crystal. By fitting the magnetization-electric field (M-E) curve, it can be found
      that the linear ([Formula: see text]) and quadratic (gamma) coefficients equal to
      ~8.27 ps/m and ~-6.46 ps/MV for upper branch, as well as ~8.38 ps/m and ~6.75
      ps/MV for the lower branch. More importantly, a pronounced response was observed
      under a small cooling magnetic field, which cannot even cause the spin flop. This
      suggests a magnetoelectric effect can occur at paraelectric state for CNO single
      crystal. Furthermore, we also found that the magnetization of every axis responds
      to electric field applied along a-axis, but fails to do so when the electric
      field is applied c-axis. Such findings supply a direct evidence to the magnetic
      structure and ME coupling mechanism indirectly reflected by our neutron
      experiment.

PMID- 29074871
TI  - UPS-indel: a Universal Positioning System for Indels.
AB  - Storing biologically equivalent indels as distinct entries in databases causes
      data redundancy, and misleads downstream analysis. It is thus desirable to have a
      unified system for identifying and representing equivalent indels. Moreover, a
      unified system is also desirable to compare the indel calling results produced by
      different tools. This paper describes UPS-indel, a utility tool that creates a
      universal positioning system for indels so that equivalent indels can be uniquely
      determined by their coordinates in the new system, which also can be used to
      compare different indel calling results. UPS-indel identifies 15% redundant
      indels in dbSNP, 29% in COSMIC coding, and 13% in COSMIC noncoding datasets
      across all human chromosomes, higher than previously reported. Comparing the
      performance of UPS-indel with existing variant normalization tools vt normalize,
      BCFtools, and GATK LeftAlignAndTrimVariants shows that UPS-indel is able to
      identify 456,352 more redundant indels in dbSNP; 2,118 more in COSMIC coding, and
      553 more in COSMIC noncoding indel dataset in addition to the ones reported
      jointly by these tools. Moreover, comparing UPS-indel to state-of-the-art
      approaches for indel call set comparison demonstrates its clear superiority in
      finding common indels among call sets. UPS-indel is theoretically proven to find
      all equivalent indels, and thus exhaustive.

PMID- 29074872
TI  - Testing scientific models using Qualitative Reasoning: Application to cellulose
      hydrolysis.
AB  - With the accumulation of scientific information in natural science, even experts
      can find difficult to keep integrating new piece of information. It is critical
      to explore modelling solutions able to capture information scattered in
      publications as a computable representation form. Traditional modelling
      techniques are important in that regard, but relying on numerical information
      comes with limitations for integrating results from distinct studies, high-level
      representations can be more suited. We present an approach to stepwise construct
      mechanistic explanation from selected scientific papers using the Qualitative
      Reasoning framework. As a proof of concept, we apply the approach to modelling
      papers about cellulose hydrolysis mechanism, focusing on the causal explanations
      for the decreasing of hydrolytic rate. Two explanatory QR models are built to
      capture classical explanations for the phenomenon. Our results show that none of
      them provides sufficient explanation for a set of basic experimental observations
      described in the literature. Combining the two explanations into a third one
      allowed to get a new and sufficient explanation for the experimental results. In
      domains where numerical data are scarce and strongly related to the experimental
      conditions, this approach can aid assessing the conceptual validity of an
      explanation and support integration of knowledge from different sources.

PMID- 29074874
TI  - Conformal QED in two-dimensional topological insulators.
AB  - It has been shown that local four-fermion interactions on the edges of two
      dimensional time-reversal-invariant topological insulators give rise to a new non
      Fermi-liquid phase, called helical Luttinger liquid (HLL). Here, we provide a
      first-principle derivation of this HLL based on the gauge-theory approach. We
      start by considering massless Dirac fermions confined on the one-dimensional
      boundary of the topological insulator and interacting through a three-dimensional
      quantum dynamical electromagnetic field. Within these assumptions, through a
      dimensional-reduction procedure, we derive the effective 1 + 1-dimensional
      interacting fermionic theory and reveal its underlying gauge theory. In the low
      energy regime, the gauge theory that describes the edge states is given by a
      conformal quantum electrodynamics (CQED), which can be mapped exactly into a HLL
      with a Luttinger parameter and a renormalized Fermi velocity that depend on the
      value of the fine-structure constant alpha.

PMID- 29074873
TI  - Regulatory Compliant Tissue-Engineered Human Corneal Endothelial Grafts Restore
      Corneal Function of Rabbits with Bullous Keratopathy.
AB  - Corneal transplantation is the only treatment available to restore vision for
      individuals with blindness due to corneal endothelial dysfunction. However,
      severe shortage of available donor corneas remains a global challenge. Functional
      regulatory compliant tissue-engineered corneal endothelial graft substitute can
      alleviate this reliance on cadaveric corneal graft material. Here, isolated
      primary human corneal endothelial cells (CEnCs) propagated using a dual media
      approach refined towards regulatory compliance showed expression of markers
      indicative of the human corneal endothelium, and can be tissue-engineered onto
      thin corneal stromal carriers. Both cellular function and clinical adaptability
      was demonstrated in a pre-clinical rabbit model of bullous keratopathy using a
      tissue-engineered endothelial keratoplasty (TE-EK) approach, adapted from routine
      endothelial keratoplasty procedure for corneal transplantation in human patients.
      Cornea thickness of rabbits receiving TE-EK graft gradually reduced over the
      first two weeks, and completely recovered to a thickness of approximately 400 um
      by the third week of transplantation, whereas corneas of control rabbits remained
      significantly thicker over 1,000 um (p < 0.05) throughout the course of the
      study. This study showed convincing evidence of the adaptability of the
      propagated CEnCs and their functionality via a TE-EK approach, which holds great
      promises in translating the use of cultured CEnCs into the clinic.

PMID- 29074875
TI  - Terahertz beam switching by electrical control of graphene-enabled tunable
      metasurface.
AB  - Controlling the terahertz wave, especially the dynamical and full control of
      terahertz wavefront, is highly demanded due to the increasing development of
      practical devices and application systems. Recently considerable efforts have
      been made to fill the 'terahertz gap' with the help of artificial metamaterial or
      metasurface incorporated with graphene material. Here, we propose a scheme to
      design tunable metasurface consisting of metallic patch array on a grounded
      polymer substrate embedded with graphene layers to electrically control the
      electromagnetic beam reflection at terahertz frequency. By adjusting geometric
      dimension of the patch elements, 360 degree reflection phase range may be
      achieved, thus abrupt phase shifts can be introduced along the metasurface for
      tailoring the reflected wavefront. Moreover, the reflective phase gradient over
      the metasurface can be switched between 90 and 360 degree by controlling the
      Fermi energy of the embedded graphene through voltage biasing, hence dynamically
      switching the reflective beam directions. Numerical simulations demonstrate that
      either single beam or dual beam dynamically switching between normal and oblique
      reflection angles can be well attained at working frequency. The proposed
      approach will bring much freedom in the design of beam manipulation devices and
      may be applied to terahertz radiation control.

PMID- 29074876
TI  - Effects of seedling age and cultivation density on agronomic characteristics and
      grain yield of mechanically transplanted rice.
AB  - Delayed transplantation frequently occurs in mechanically transplanted rice in
      China, leading to a significant reduction in grain yield. Thus, determining how
      to compensate grain yield loss is crucial for improving rice cultivation
      technology. A field experiment was conducted to investigate the effects of
      cultivation density and seedling age on agronomic traits and grain yield of
      mechanically transplanted rice. With increasing seedling age, rice tiller number,
      pre-anthesis dry matter accumulation, remobilization efficiency and contribution
      to grain yield, as well as post-anthesis photosynthesis amount decreased, causing
      reductions in the number of effective panicles, the total number of grains per
      panicle, the sink capacity per tiller, and grain yield. In rice transplanted at
      30- and 35-day seedling ages, increasing cultivation density significantly
      enhanced the number of effective panicles and grain yield. Additionally, there
      existed strong, positive correlations between sink capacity per tiller and pre
      anthesis dry matter remobilization efficiency and pre-anthesis dry matter
      contribution to grain yield. We conclude that in addition to cultivation density,
      enhancing the amount of pre-anthesis dry matter and the remobilization efficiency
      could be feasible for mitigating grain yield loss caused by delayed
      transplantation.

PMID- 29074877
TI  - A single episode of high intensity sound inhibits long-term potentiation in the
      hippocampus of rats.
AB  - Exposure to loud sounds has become increasingly common. The most common
      consequences of loud sound exposure are deafness and tinnitus, but emotional and
      cognitive problems are also associated with loud sound exposure. Loud sounds can
      activate the hipothalamic-pituitary-adrenal axis resulting in the secretion of
      corticosterone, which affects hippocampal synaptic plasticity. Previously we have
      shown that long-term exposure to short episodes of high intensity sound inhibited
      hippocampal long-term potentiation (LTP) without affecting spatial learning and
      memory. Here we aimed to study the impact of short term loud sound exposure on
      hippocampal synaptic plasticity and function. We found that a single minute of
      110 dB sound inhibits hippocampal Schaffer-CA1 LTP for 24 hours. This effect did
      not occur with an 80-dB sound exposure, was not correlated with corticosterone
      secretion and was also observed in the perforant-dentate gyrus synapse. We found
      that despite the deficit in the LTP these animals presented normal spatial
      learning and memory and fear conditioning. We conclude that a single episode of
      high-intensity sound impairs hippocampal LTP, without impairing memory and
      learning. Our results show that the hippocampus is very responsive to loud sounds
      which can have a potential, but not yet identified, impact on its function.

PMID- 29074878
TI  - A guanidine-appended scyllo-inositol derivative AAD-66 enhances brain delivery
      and ameliorates Alzheimer's phenotypes.
AB  - Alzheimer's disease (AD) is a degenerative brain disease that destroys memory and
      other important mental functions but lacks efficient therapeutic agents. Blocking
      toxic amyloid beta (Abeta) could be beneficial for AD and represents a promising
      therapeutic strategy for AD treatment. scyllo-Inositol (SI) is a potential
      therapeutic for AD by directly interacting with the Abeta peptide to inhibit
      Abeta42 fiber formation. Clinical studies of SI showed promising benefits on mild
      to moderate AD, however, with limitations on dosage regime. A new strategy to
      enhance the brain delivery of SI is needed to achieve the efficacy with minimum
      adverse effects. Herein, we report that a novel guanidine-appended SI derivative
      AAD-66 resulted in more effective reductions of brain Abeta and plaque deposits,
      gliosis, and behavioral memory deficits in the disease-established 5xFAD mice.
      Overall, our present study reveals the potential of AAD-66 as a promising
      therapeutic agent for AD.

PMID- 29074879
TI  - The Role of Autophagy in Critical Illness-induced Liver Damage.
AB  - Mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which activates
      the unfolded protein response (UPR), mediate critical illness-induced organ
      failure, often affecting the liver. Autophagy is known to alleviate both and
      suppressed or insufficiently activated autophagy in prolonged illness has shown
      to associate with organ failure. Whether insufficient autophagy contributes to
      organ failure during critical illness by affecting these underlying mechanisms is
      incompletely understood. In this study, we investigated whether the inability to
      acutely activate hepatic autophagy during critical illness aggravates liver
      damage by increasing hepatic mitochondrial dysfunction and affecting the UPR. In
      a mouse model of critical illness, induced by surgery and sepsis, we investigated
      the impact of inactivating hepatic autophagy on markers of hepatic mitochondrial
      function, the UPR and liver damage in acute (1 day) and prolonged (3 days)
      critical illness. Hepatic autophagy inactivation during critical illness acutely
      worsened mitochondrial dysfunction and time-dependently modulated the hepatic
      UPR. Furthermore, autophagy inactivation aggravated markers of liver damage on
      both time points. In conclusion, the inability to acutely activate autophagy in
      liver during critical illness worsened hepatic mitochondrial damage and
      dysfunction, partially prohibited acute UPR activation and aggravated liver
      damage, indicating that autophagy is crucial in alleviating critical illness
      induced organ failure.

PMID- 29074881
TI  - Rancher-reported efficacy of lethal and non-lethal livestock predation mitigation
      strategies for a suite of carnivores.
AB  - Pastoralists have dealt with livestock losses from predators for millennia, yet
      effective mitigation strategies that balance wildlife conservation and
      sustainable agriculture are still needed today. In Wyoming, USA, 274 ranchers
      responded to a retrospective survey, and rated the efficacy of predation
      mitigation strategies for foxes, dogs, coyotes, wolves, bobcats, mountain lions,
      bears, and birds (buzzards, eagles, hawks, ravens). Rancher reported efficacy of
      mitigation varied by predator species, mitigation strategy, and lethality of
      strategies, but not livestock type. Ranchers perceive they were most effective at
      mitigating predation by foxes and coyotes, moderately effective at mitigating
      large carnivores, and the least effective at mitigating birds. Ranchers also
      reported that avian predators seem to be the most challenging predator type. The
      general perception was lethal mitigation strategies were more effective than non
      lethal strategies, with guard animals showing the most potential among the non
      lethal options. In general, ranchers did not perceive non-lethal strategies as a
      proxy for lethal strategies. However, a few ranchers reported being successful
      with non-lethal options such as herding, fencing, and stalling at night but more
      details about such successful applications are needed. Innovation in current or
      novel non-lethal mitigation strategies, and examples of efficacy, are needed to
      justify producer adoption.

PMID- 29074880
TI  - Examining the human infectious reservoir for Plasmodium falciparum malaria in
      areas of differing transmission intensity.
AB  - A detailed understanding of the human infectious reservoir is essential for
      improving malaria transmission-reducing interventions. Here we report a multi
      regional assessment of population-wide malaria transmission potential based on
      1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across
      both sites, we identified 39 infectious individuals. In high endemicity settings,
      infectious individuals were identifiable by research-grade microscopy (92.6%;
      25/27), whilst one of three infectious individuals in the lowest endemicity
      setting was detected by molecular techniques alone. The percentages of infected
      mosquitoes in the different surveys ranged from 0.05 (4/7716) to 1.6% (121/7749),
      and correlate positively with transmission intensity. We also estimated exposure
      to malaria vectors through genetic matching of blood from 1094 wild-caught
      bloodfed mosquitoes with that of humans resident in the same houses. Although
      adults transmitted fewer parasites to mosquitoes than children, they received
      more mosquito bites, thus balancing their contribution to the infectious
      reservoir.

PMID- 29074882
TI  - Liposome-encapsulated plasmid DNA of telomerase-specific oncolytic adenovirus
      with stealth effect on the immune system.
AB  - Oncolytic virotherapy has the disadvantage of being unsuitable for systemic
      delivery due to immune elimination. Liposomal encapsulation is well-recognized to
      reduce immune elimination and enhance the stability of drugs in the bloodstream.
      In the present study, the potential of liposome-encapsulated plasmid DNA of
      telomerase-specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS)
      as an oncolytic adenoviral agent suitable for systemic delivery was investigated.
      Lipo-pTS, which has a diameter of 40-50 nm, showed potent antitumor effects on
      HCT116 colon carcinoma cells in vitro and in vivo. Tumor selectivity of Lipo-pTS
      was independent of coxsackie and adenovirus receptor (CAR). Importantly, Lipo-pTS
      reduced production of adenovirus-neutralizing antibodies (AdNAbs) after
      intravenous administration into immune-competent mice compared to TelomeScan, and
      even in the presence of AdNAbs, Lipo-pTS maintained strong cytotoxicity. In
      conclusion, Lipo-pTS has the potential to become an oncolytic adenoviral agent
      suitable for systemic delivery with the characteristics of CAR-independent
      antitumor activity and a stealth effect on the immune system.

PMID- 29074883
TI  - Bi-component T1rho and T2 Relaxation Mapping of Skeletal Muscle In-Vivo.
AB  - The goal of this paper was to evaluate the possibility of bi-component T1rho and
      T2 relaxation mapping of human skeletal muscle at 3 T in clinically feasible scan
      times. T1rho- and T2-weighted images of calf muscle were acquired using a
      modified 3D-SPGR sequence on a standard 3 T clinical MRI scanner. The mono- and
      biexponential models were fitted pixel-wise to the series of T1rho and T2
      weighted images. The biexponential decay of T1rho and T2 relaxations was detected
      in ~30% and ~40% of the pixels across all volunteers, respectively.
      Monoexponential and bi-exponential short and long T1rho relaxation times were
      estimated to be 26.9 ms, 4.6 ms (fraction 22%) and 33.2 ms (fraction: 78%),
      respectively. Similarly, the mono- and bi-exponential short and long T2
      relaxation times were 24.7 ms, 4.2 ms (fraction 15%) and 30.4 ms (fraction 85%)
      respectively. The experiments had good repeatability with RMSCV < 15% and ICC >
      60%. This approach could potentially be used in exercise intervention studies or
      in studies of inflammatory myopathies or muscle fibrosis, permitting greater
      sensitivity and specificity via measurement of different water compartments and
      their fractions.

PMID- 29074884
TI  - Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral
      Contraceptives.
AB  - Using oral contraceptives has been implicated in the aetiology of stress-related
      disorders like depression. Here, we followed the hypothesis that oral
      contraceptives deregulate the HPA-axis by elevating circulating cortisol levels.
      We report for a sample of 233 pre-menopausal women increased circulating cortisol
      levels in those using oral contraceptives. For women taking oral contraceptives,
      we observed alterations in circulating phospholipid levels and elevated
      triglycerides and found evidence for increased glucocorticoid signalling as the
      transcript levels of the glucocorticoid-regulated genes DDIT4 and FKBP5 were
      increased in whole blood. The effects were statistically mediated by cortisol.
      The associations of oral contraceptives with higher FKBP5 mRNA and altered
      phospholipid levels were modified by rs1360780, a genetic variance implicated in
      psychiatric diseases. Accordingly, the methylation pattern of FKBP5 intron 7 was
      altered in women taking oral contraceptives depending on the rs1360780 genotype.
      Moreover, oral contraceptives modified the association of circulating cortisol
      with depressive symptoms, potentially explaining conflicting results in the
      literature. Finally, women taking oral contraceptives displayed smaller
      hippocampal volumes than non-using women. In conclusion, the integrative analyses
      of different types of physiological data provided converging evidence indicating
      that oral contraceptives may cause effects analogous to chronic psychological
      stressors regarding the regulation of the HPA axis.